PMID- 22067176 TI - The impact of obesity on outcomes following major surgery for Crohn's disease: an American College of Surgeons National Surgical Quality Improvement Program assessment. AB - BACKGROUND: Whereas Crohn's disease is traditionally thought to represent a wasting disease, little is currently known about the incidence and impact of obesity in this patient cohort. OBJECTIVE: This study aimed to evaluate the perioperative outcomes in patients with Crohn's disease who were obese vs those who were not obese undergoing major abdominal surgery. DESIGN: This study is a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database (2005-2008). Risk-adjusted 30-day outcomes were assessed by the use of regression modeling accounting for patient characteristics, comorbidities, and surgical procedures. PATIENTS: Included were all patients with Crohn's disease who were undergoing abdominal operations. MAIN OUTCOME MEASURE: The primary outcomes measured were short-term perioperative outcomes. Obesity was defined as a BMI of 30 or greater. RESULTS: We identified 2319 patients (mean age, 41.6 y; 55% female). Of these patients, 379 (16%) met obesity criteria, 2% were morbidly obese, and 0.3% were super obese. Rates of obesity significantly increased each year over the study period. Twenty-five percent of the surgeries were performed laparoscopically (obese 21% vs nonobese 26%). Six percent were emergent, with no difference in patients with obesity. Operative times were significantly longer among patients with obesity (177 min) compared with patients who were not obese (164 min). After adjusting for differences in comorbidities and steroid use, overall perioperative morbidity was significantly higher in the obese cohort (32% vs 22% nonobese; OR 1.9). In addition, the rates of postoperative complications increased directly with rising BMI. Irrespective of procedure type, the patients who were obese were significantly more likely to experience wound infections (OR 1.7), which increased even further in patients who were morbidly obese (BMI >40; OR 7.1). By specific operation, postoperative morbidity was increased in patients with obesity following colectomies with primary anastomosis for both open and laparoscopic approaches (OR 2.9 and OR 3.8). Cardiac, pulmonary, and renal complications as well as overall mortality did not differ significantly based on BMI. LIMITATIONS: This study was limited by being a retrospective review, and by using data limited to the American College of Surgeons National Surgical Quality Improvement Program database. CONCLUSION: Increasing BMI adversely affects perioperative morbidity in patients with Crohn's disease. PMID- 22067177 TI - Risk of postoperative venous thromboembolism after laparoscopic and open colorectal surgery: an additional benefit of the minimally invasive approach? AB - BACKGROUND: Venous thromboembolism constitutes a major cause of morbidity associated with surgical procedures. Colorectal surgical patients are at an elevated risk for postoperative venous thromboembolism. Whether the laparoscopic approach influences this risk is not well defined. OBJECTIVE: This study aimed to assess the risk of venous thromboembolism following major colorectal procedures. The influences of laparoscopic and open approaches on venous thromboembolism were compared while controlling for other potential confounders. DESIGN: Patients who underwent major colorectal procedures were identified. Association between patient, disease, operation-related factors, and venous thromboembolism within 30 days of surgery was determined by the use of a logistic regression analysis. SETTINGS: Patients were identified from the National Surgical Quality Improvement Program database (2005-2008). PATIENTS: According to the National Surgical Quality Improvement Program database, 31,109 patients underwent colorectal surgery (open, 71%; laparoscopic, 29%) for cancer (48.3%), IBD (10.1%), diverticular disease (24.2%), and other benign conditions (17.4%). MAIN OUTCOME MEASURES: The primary outcomes measured were deep venous thrombosis and pulmonary embolism. RESULTS: The venous thromboembolism rate was 2.4% (laparoscopic 1.2% vs open 2.9%, P < .001). Patients who developed venous thromboembolism were older (age 65.4 vs 61.5, P < .001), more often male (52.5% vs 47.5%, P = .023), with worse functional status (P < .001), and more comorbidities (P < .001). Venous thromboembolism was associated with sepsis (7.9% vs 1.8%, P < .001), steroid use (5.4% vs 2.2%, P < .001), surgical site infection (4.8% vs 2%, P < .001), and reoperation (7% vs 2.1%, P < .001). On multivariate analysis, open surgery, older age, steroid use, sepsis, surgical site infection, reoperation, prolonged ventilation, and low albumin were independently associated with a higher venous thromboembolism rate. LIMITATIONS: The details regarding determinants of the decision for laparoscopic surgery, conversion rates for laparoscopic procedures, and thrombosis prophylaxis regimens were not available. CONCLUSIONS: The laparoscopic approach is associated with a lower venous thromboembolism rate in comparison with open surgery, despite controlling for other variables. This additional benefit of the minimally invasive approach further supports its use, whenever feasible, for a variety of colorectal conditions. PMID- 22067178 TI - The anatomical and surgical consequences of right colectomy for cancer. AB - BACKGROUND: Current practice when performing right colectomy for cancer is to divide the feeding vessels for the right colon on the right side of the superior mesenteric vein. OBJECTIVE: This study aims to show that arterial stumps can be visualized through an early postoperative CT and analyze their anatomical and surgical characteristics. DESIGN: This study presents a retrospective review of prospective data. SETTINGS: :The study was conducted at the Department of Surgery, Vestfold Hospital, Tonsberg, Norway. PATIENTS: Patients with leakage after a right colectomy for cancer (2003-2011) were identified through a local prospective complication registry (FileMaker Pro 9.0v3 software). INTERVENTIONS: Both preoperative and postoperative CTs were retrieved, reanalyzed, and 3 dimensionally reconstructed (Osirix v.3.0.2./Mimics v.13.1.). Patients without postoperative CTs were excluded. MAIN OUTCOME MEASURES: The main outcomes measured were length, caliber of presumed and actual arterial stumps, and their position relative to the superior mesenteric vein. RESULTS: Eighteen patients, median age 69 (10 men) were included. All patients had postoperative CTs, and 15 patients had preoperative CTs. Median time from operation to postoperative CT was 5 days. The ileocolic artery was found in 14 (11 CT pairs) patients, and the right colic artery was found in 5 (4 pairs) patients. Actual stump lengths were 28.0 mm (SD 9.3) and 37.3 mm (SD 14.9). A significant statistical difference between presumed and actual ileocolic artery stump lengths was found (P = .002). Posterior crossing to the superior mesenteric vein was noticed in 8 of 14 ileocolic arteries and in 3 of 5 right colic arteries. There was no statistical difference in mean caliber for the preoperative and postoperative right colic artery (P = .505) and ileocolic artery (P = .474). LIMITATIONS: Difficulties when interpreting the postoperative images, due to intra-abdominal effusion, staples, edema, and altered syntopy of blood vessels, were overcome through comparison with preoperative CTs. CONCLUSION: An early postoperative CT can show arterial stumps after right colectomy for cancer. These stumps appear to be significantly longer than presumed; implying a significant improvement potential when specimen size is concerned. PMID- 22067179 TI - Intramural and mesorectal distal spread detected by whole-mount sections in the determination of optimal distal resection margin in patients undergoing surgery for rectosigmoid or rectal cancer without preoperative therapy. AB - BACKGROUND: The current Japanese general rules for clinical and pathologic studies on cancer of the colon, rectum, and anus state that a 3-cm distal resection margin is needed in resecting rectosigmoid cancer and rectal cancer with a distal edge above the peritoneal reflection, and 2 cm is needed for rectal cancer with a distal edge below the peritoneal reflection. The appropriateness of these rules has not been proved. OBJECTIVE: Our aim was to evaluate the appropriateness of the Japanese rules. DESIGN AND SETTING: We retrospectively analyzed surgical and pathology records of patients who underwent surgery at a tertiary care cancer center in Japan. PATIENTS: The study included 381 consecutive patients with stage I to IV rectosigmoid or rectal cancer without preoperative chemotherapy or radiotherapy. MAIN OUTCOME MEASURES: We investigated both intramural and mesorectal distal spread, using whole-mount sections to measure the maximum length of distal spread. Long distal spread was defined as distal spread longer than the distal resection margin stated in the Japanese general rules. Risk factors for both distal spread and long distal spread were evaluated. RESULTS: Of 381 patients, 325 (85.3%) had no distal spread and a total of 56 (14.7%) had distal spread. Distal spread was within the limits specified by the Japanese general rules in 48 of the 381 patients (12.6%) and beyond the Japanese limits (long distal spread) in 8 patients (2.1%). The prevalence of distal spread increased with TNM stage (stage I, 2.7%; stage II, 5.3%; stage III, 17.4%; stage IV, 46.2%). Long distal spread was not observed in stage I or II, was found in only 1.4% of patients with stage III disease and in 11.5% of patients with stage IV. The maximum extent of distal spread in patients with rectosigmoid cancer or rectal cancer with the distal edge above the peritoneal reflection was 38 mm; in patients with rectal cancer with the distal edge below the peritoneal reflection, 35 mm. Multivariable analyses showed that nodal involvement and distant metastasis were independent risk factors for distal spread; distant metastasis was the only independent risk factor for long distal spread. CONCLUSIONS: The Japanese general rules specifying the distal resection margin are appropriate for most patients who undergo surgery for rectosigmoid and rectal cancer without preoperative chemotherapy or radiotherapy. A further increase of 1 to 2 cm beyond the recommended distal resection margin may contribute to improved local control for patients with distant metastasis. PMID- 22067180 TI - Long-term follow-up features on rectal MRI during a wait-and-see approach after a clinical complete response in patients with rectal cancer treated with chemoradiotherapy. AB - BACKGROUND: The "wait-and-see" policy instead of standard surgery for patients with rectal cancer who undergo a complete tumor regression after chemoradiation treatment is highly controversial. It is not clear yet how patients should be monitored once they are managed nonoperatively and whether follow-up by MRI has any potential role. OBJECTIVE: This study aimed to describe the rectal wall MRI morphology during short-term and long-term follow-up in patients with a clinical complete tumor response undergoing a wait-and-see policy without surgical treatment. DESIGN, SETTING, AND PATIENTS: As part of an observational study in our center, a cohort of 19 carefully selected patients with a clinical complete response after chemoradiation was managed with a wait-and-see policy and followed regularly (every 3-6 mo) by clinical examination, endoscopy with biopsies, and a rectal MRI. The MR morphology of the tumor bed was studied on the consecutive MRI examinations. MAIN OUTCOME MEASURES: The primary outcome measured was the morphology of the tumor bed on the consecutive MRI examinations performed during short-term (<=6 mo) and long-term (>6 mo) follow-up. RESULTS: Patients with a complete tumor response after chemoradiation presented with either a normalized rectal wall (26%) or fibrosis (74%). In the latter group, 3 patterns of fibrosis were observed (full-thickness, minimal, or spicular fibrosis). The morphology patterns of a normalized rectal wall or fibrosis remained consistent during long term follow-up in 18 of 19 patients. One patient developed a small, endoluminal recurrence, which was salvaged with transanal endoscopic microsurgery. In 26% of patients, an edematous wall thickening was observed in the first months after chemoradiation, which gradually decreased during long-term follow-up. Median follow-up was 22 months (range, 12-60). LIMITATIONS: This was a small observational study, and had no histological validation. CONCLUSIONS: Four MR patterns of a persistent complete response of rectal cancer after chemoradiation were identified. These MR features can serve as a reference for the follow-up in a wait-and-see policy. PMID- 22067181 TI - Proximity to disease and perception of utility: physicians' vs patients' assessment of treatment options for ulcerative colitis. AB - BACKGROUND: Physician values regarding the benefit of continued medical therapy vs colectomy for moderate ulcerative colitis have not been defined. If physicians perceive these states differently than patients, their therapeutic recommendations may not align with patient values. OBJECTIVE: This study aimed to compare physician and patient willingness to trade life years with moderately active ulcerative colitis vs undergoing colectomy. DESIGN: This survey of physicians' and patients' utility values used standardized scenarios for moderately active ulcerative colitis and colectomy. SETTING: The investigation was conducted at a tertiary academic medical center. METHODS: Gastroenterologists, colorectal surgeons, and patients with ulcerative colitis who were either living with moderate disease or were postcolectomy completed the survey. MAIN OUTCOME MEASURES: Utility values were measured by the use of the time trade-off method. RESULTS: We surveyed 17 physicians, 150 postcolectomy patients, and 69 patients with moderate ulcerative colitis. Utility values for ulcerative colitis and colectomy states were (0.87, 0.95), (0.86, 0.92), and (0.91, 0.91). On average, physicians and postcolectomy patients assessed the utility of life with ulcerative colitis more poorly than the postcolectomy state. Patients with moderately active ulcerative colitis who had not undergone colectomy viewed both health states equally. LIMITATIONS: This study was limited by the physician subject sample size. CONCLUSIONS: Patients living with moderate ulcerative colitis value the pre- and postcolectomy states differently than physicians and postcolectomy patients. Recognizing the differences between their own and patients' values may help physicians to better counsel patients preoperatively. In addition, exposure to postcolectomy patients may help those with moderate disease who are weighing the comparative benefits of colectomy. PMID- 22067182 TI - Advancement flap repair: a good option for complex anorectal fistulas. AB - BACKGROUND: Rectal advancement flap is a popular option for treatment of complex anal fistula. Although early outcomes vary, concerns remain about postoperative continence, long-term healing, and its role in patients with Crohn's disease and anovaginal fistulas. PURPOSE: This study aimed to report long-term outcomes in patients with complex fistula disease. PATIENTS: Patients who were undergoing rectal advancement flap for anal fistula were included in the study. DESIGN: Patients were contacted to determine the status of their fistula disease, their bowel function, and their degree of fecal incontinence. MAIN OUTCOME MEASURES: The main outcomes measured were healing rate and continence. RESULTS: There were 98 patients, 43 men and 55 women, mean age 53 +/- 14 years. Fifty-eight had cryptoglandular fistulas, and 40 (41%) had IBD (33 had Crohn's disease). Seventy seven of 98 patients had perianal fistulas, and all 77 underwent seton drainage before advancement flap. Twenty-one women had anovaginal fistulas. Average postoperative length of stay was 3 +/- 1 days. There were no mortalities. Follow up was possible in 75 patients, a mean of 7 +/- 3 years after surgery. Primary healing occurred in 54 (72%) patients. Twenty-one patients (28%) underwent further treatment, and 12 (57%) healed after a second advancement flap. Four more patients healed after more than 2 flaps or fistulotomy leading to an overall healing rate of 70 of 75 (93%). Patients with Crohn's disease had lower healing rates than those with cryptoglandular fistulas (87% vs 98%). Thirty-two patients (43%) had normal fecal continence before flap, and 43 (57%) had normal fecal continence after flap. CONCLUSION: Advancement flap is a good option for patients with complex anal fistulas. PMID- 22067183 TI - Scarless single-incision laparoscopic loop ileostomy: a novel technique. AB - BACKGROUND: Laparoscopic surgery has become a favorable alternative to conventional open surgery for the creation of intestinal stomas, and it offers many benefits including reduced postoperative pain, ileus, and hospital stay. Single-incision laparoscopic surgery has been described for many abdominal operations. It may offer better cosmetic outcomes and reduce incisional pain, adhesions, and recovery time. OBJECTIVE: In this study, we aimed to describe a novel technique of scarless single-incision laparoscopic loop ileostomy for fecal diversion and to report our experience with 8 patients who underwent this procedure within a 1-year period. DESIGN: This study was designed as a retrospective case series. SETTINGS: This investigation was conducted at a single institution, tertiary referral center. PATIENTS: Eight consecutive patients undergoing scarless single-incision laparoscopic loop ileostomy between August 2009 and August 2010 were included. INTERVENTION: Scarless single-incision laparoscopic loop ileostomies were performed. MAIN OUTCOME MEASURES: Among the outcomes measured were operation time, intraoperative blood loss, recovery of intestinal function, length of hospital stay, and surgical complications. RESULTS: Seven patients underwent surgery for active Crohn's disease refractory to medical therapy. One patient underwent surgery for radiation-induced rectovesical fistula. Median surgery time was 76 minutes, and median intraoperative blood loss was 10 mL. Median length of postoperative hospitalization was 7 days. Of the 8 patients included in our series, 2 patients (25%) required reoperation for stoma ischemia because of vascular congestion that we attribute to a tight fascial opening or extensive bowel manipulation. Other surgical complications included nonoperative readmission for ileus and partial small-bowel obstruction (n = 2), anal dilation to evacuate an obstructed distal colon (n = 1), and peristomal cellulitis (n = 1). LIMITATIONS: This study was limited by its small sample size and its retrospective nature. CONCLUSION: Scarless single-incision laparoscopic loop ileostomy is a feasible alternative to standard laparoscopy for fecal diversion. Surgeons attempting this technique should do so with caution, given the high stoma ischemia rate in our small case series. PMID- 22067184 TI - Peutz-Jeghers syndrome: intriguing suggestion of gastrointestinal cancer prevention from surveillance. AB - BACKGROUND: Peutz-Jeghers syndrome is characterized by GI polyps and mucocutaneous pigmentation and carries an increased risk of GI cancer. GI polyps may bleed or cause intussusception. Luminal GI surveillance is recommended, but there are few data detailing outcomes from GI surveillance in Peutz-Jeghers syndrome. OBJECTIVE: This study aimed to assess outcomes from GI surveillance in patients with Peutz-Jeghers syndrome. DESIGN: This study is a retrospective review, using hospital and registry notes and endoscopy and histology reports. SETTING: The investigation was conducted at a tertiary referral center. PATIENTS: All patients with Peutz-Jeghers syndrome who were followed up at St Mark's hospital were included. MAIN OUTCOME MEASURES: The primary outcomes measured were surveillance procedures performed, complications, and long-term outcomes. RESULTS: Sixty-three patients from 48 pedigrees were included; the median age when patients were first seen was 20 years (range, 3-59). Only baseline investigations were performed in 12 patients. The remaining patients were followed up for 683 patient years, a median of 10 years (range, 2-41). Seven hundred seventy-six procedures were performed to assess the GI tract. These led to 5 double-balloon enteroscopies, 1 push enteroscopy, and 71 surgical procedures. Of the surgical procedures, 20 were performed as a result of baseline investigations, 12 arose from investigations of symptoms, and 39 were due to surveillance of asymptomatic patients. No emergency surgical interventions were performed. No luminal GI cancers were diagnosed. Of the 2461 polypectomies performed, 6 polyps contained atypia or dysplasia. Six complications arose from endoscopy or surgical intervention, requiring 5 laparotomies to manage these complications. CONCLUSION: GI surveillance in Peutz-Jeghers syndrome is relatively safe and avoids the need for emergency surgery for small-bowel polyps. The lack of GI cancers may reflect that surveillance and polypectomy have prevented cancer from developing, although the detection of neoplasia or dysplasia is uncommon. PMID- 22067185 TI - Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. AB - BACKGROUND: Bupivacaine extended-release liposome injection is a novel formulation of bupivacaine designed to achieve long-acting postoperative analgesia. OBJECTIVE: The aim of this study was to compare the magnitude and duration of postoperative analgesia from a single dose of bupivacaine extended release injection with placebo administered intraoperatively in patients undergoing hemorrhoidectomy. DESIGN: This evaluation was a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 study. SETTINGS: Data were obtained from 13 centers in the Republic of Georgia, Poland, and Serbia. PATIENTS: Included in this study were patients aged 18 to 86 years undergoing excisional hemorrhoidectomy. INTERVENTIONS: All patients received either a single dose of bupivacaine extended-release 300 mg or placebo administered intraoperatively via wound infiltration. MAIN OUTCOME MEASURE: The cumulative pain score was assessed by measurement of the area under the curve of pain intensity through 72 hours after study drug administration. RESULTS: One hundred eighty-nine patients were randomly assigned and treated; 186 completed the study. Pain intensity scores were significantly lower in the bupivacaine extended-release group in comparison with the group receiving placebo (141.8 vs 202.5, P < .0001). More patients in the bupivacaine extended-release group remained opioid free from 12 hours (59%) to 72 hours (28%) after surgery compared with patients receiving placebo (14% and 10%; P < .0008 through 72 h). The mean total amount of opioids consumed through 72 hours was 22.3 mg and 29.1 mg in the bupivacaine extended-release and placebo groups (P <= .0006). The median time to first opioid use was 14.3 hours in the bupivacaine extended-release group vs 1.2 hours in the placebo group (P < .0001). A greater proportion of patients in the bupivacaine extended-release group were satisfied with their postsurgical analgesia (95% vs 73%, P = .0007) than in the placebo group. CONCLUSIONS: Bupivacaine extended-release demonstrated a statistically significant reduction in pain through 72 hours, decreased opioid requirements, delayed time to first opioid use, and improved patient satisfaction compared with placebo after hemorrhoidectomy. PMID- 22067186 TI - Prevalence and pathophysiology of functional constipation among women in Catalonia, Spain. AB - BACKGROUND: Specific treatment of functional bowel disorders requires precise diagnosis. However, prevalence and subtypes of functional constipation among women are not completely understood. OBJECTIVE: Our aim was to assess the prevalence of functional constipation and investigate the subtypes of dyssynergic defecation and slow transit constipation among Spanish women. DESIGN: We performed a prospective epidemiological study in healthy young women and retrospective pathophysiological studies in 2 patient cohorts of women with functional constipation according to Rome II criteria. SETTINGS: Referral centers at Clinica Sagrada Familia, Barcelona, Spain, and Hospital de Mataro, Mataro, Spain. PATIENTS: The epidemiological study included 600 healthy young women, aged 37.1 (SD, 8.2) years. Patient cohort 1 comprised 172 women with functional constipation without symptoms of pelvic floor dysfunction, ranging in age from 18 to 45 years. Patient cohort 2 comprised 106 women with functional constipation and symptoms of dyssynergic defecation, ranging in age from 45 to 65 years. MAIN OUTCOME MEASURES: In healthy women, a questionnaire was used to determine rates of functional constipation, dyssynergic defecation, and slow transit constipation. In patients, results of anorectal manometry, EMG, and colonic transit studies were reviewed to assess subtypes of functional constipation; in addition, results of dynamic videoproctography were reviewed in cohort 2 to assess the role of structural pelvic floor disorders. RESULTS: The prevalence of functional constipation in healthy young women was 28.8%; symptoms of dyssynergic defecation were found in 8.2%, those of isolated slow transit in only 0.17%. In patient cohort 1, a total of 143 patients (83.1%) showed dyssynergic defecation: 117 patients (68.0%) had paradoxical external anal sphincter contraction and 26 (15.1%) had impaired internal anal sphincter relaxation). Slow transit constipation without dyssynergia was observed in 15 (8.7%). Up to 40.2% of patients with dyssynergia also had delayed colonic transit. In the cohort of 106 women with dyssynergic defecation, videoproctography showed impaired puborectal relaxation in 64 patients (60.4%), anterior rectocele in 65 (61.3%), and rectal prolapse in 13 (12.3%). LIMITATIONS: We could not estimate the prevalence and subtypes of irritable bowel syndrome in the epidemiological study. CONCLUSIONS: Functional constipation is extremely prevalent among young, healthy, Spanish women, dyssynergic defecation being the most prevalent subtype. Slow transit constipation without dyssynergic defecation is uncommon. Structural pelvic floor disorders are highly prevalent in middle-aged women with dyssynergic defecation. PMID- 22067187 TI - Different bowel preparation schedule leads to different diagnostic yield of proximal and nonpolypoid colorectal neoplasm at screening colonoscopy in average risk population. AB - BACKGROUND: Accumulating evidence indicates that the timing of bowel preparation is crucial, but its impact on the diagnostic yield of proximal or nonpolypoid colorectal neoplasm remains unclear. OBJECTIVE: This study aimed to investigate the impact of the timing of bowel preparation on the adenoma detection rate for nonpolypoid colorectal neoplasm at colonoscopy. DESIGN: This study is a retrospective analysis of a screening colonoscopy cohort database. SETTING: The investigation was conducted at a screening colonoscopy unit in an university hospital. PATIENTS: A consecutive series of 3079 subjects who received primary screening colonoscopy with different timing of bowel preparation was analyzed. INTERVENTION: Different timing of bowel preparation (same day vs prior day) was studied. MAIN OUTCOME MEASURES: The main outcomes measured were patient demographics, timing of bowel preparation, colon-cleansing levels, diagnostic yields of colonoscopy, including adenoma, advanced adenoma, and nonpolypoid colorectal neoplasm. RESULTS: There were a total of 1552 subjects in the morning group and 1527 in the evening group. More subjects had proximal adenoma (175, 11.3% vs 138, 9.0%, P = .04), advanced adenoma (68, 4.4% vs 46, 13.0%, P = .044), nonpolypoid colorectal neoplasm (98, 6.3% vs 67, 4.4%, P = .018), proximal nonpolypoid colorectal neoplasm (71, 4.6% vs 40, 2.6%, P = .004), and advanced nonpolypoid colorectal neoplasm (25, 1.6% vs 12, 0.8%, P = .036) detected by same day preparation. On multivariate regression analysis, the adenoma detection rate was significantly higher in the same-day group regarding overall and proximal adenoma (OR 1.23, 95% CI: 1.00-1.50; OR 1.35, 95% CI: 1.05-1.74), advanced adenoma (OR 1.53, 95% CI: 1.04-2.28), overall, proximal, and advanced nonpolypoid colorectal neoplasm (OR 1.48, 95% CI: 1.06-2.08; OR 1.82, 95% CI: 1.20-2.75; OR 1.96, 95% CI: 1.12-3.37). The adenoma detection rate was also significantly different among endoscopists. LIMITATION: This was a single-center, nonrandomized trial. CONCLUSIONS: Improving bowel preparation quality by same-day preparation may lead to enhanced detection of overall, proximal, and advanced nonpolypoid colorectal neoplasm. PMID- 22067188 TI - Usefulness of an intensive bowel cleansing strategy for repeat colonoscopy after preparation failure. AB - BACKGROUND: No consensus exists regarding the optimal bowel preparation regimen for patients with poor bowel cleansing at a previous colonoscopy. OBJECTIVE: We investigated the usefulness of an intensive cleansing regimen for repeat colonoscopy after previous failure of bowel preparation. DESIGN AND SETTING: A prospective observational study was performed in patients undergoing colonoscopy at a university-based, tertiary referral hospital. PATIENTS AND INTERVENTION: Outpatients with inadequate preparation at an index colonoscopy were offered a repeat colonoscopy and instructed to follow an intensive preparation regimen consisting of a low-fiber diet for 72 hours, liquid diet for 24 hours, bisacodyl (10 mg) in the evening of the day before the colonoscopy, and a split dose of polyethylene glycol (1.5 L in the evening before and 1.5 L in the morning on the day of the colonoscopy). MAIN OUTCOME MEASURES: The adequacy of bowel cleansing was assessed according to the Boston Bowel Preparation Scale (0 or 1 on any colon segment = inadequate bowel preparation). Procedural variables, detection rates for polyps and adenomas, compliance, and tolerability of the regimen were assessed. Satisfaction with the regimen was assessed with a 10-point visual analog scale. RESULTS: Of 83 patients with inadequate bowel preparation at colonoscopy, 51 underwent a second colonoscopy and were analyzed; 46 patients (90.2%) had adequate bowel cleansing at the second colonoscopy, with a mean (SD) total Boston Bowel Preparation Scale score of 7.43 (1.5) and scores of 2.31 (0.6) for the right colon, 2.49 (0.6) for the transverse colon, and 2.63 (0.6) for the left colon. Polyps, flat lesions, or flat lesions proximal to the splenic flexure were found in significantly more patients at the second colonoscopy than at the index colonoscopy. The global satisfaction score was 6.6 (2.7). LIMITATIONS: The study was limited because of its open observational design, possible patient learning effect for bowel preparation at the repeat colonoscopy, and the inclusion of only outpatients. CONCLUSIONS: An intensive regimen consisting of a low-fiber diet, bisacodyl, and a split dose of polyethylene glycol can achieve good colon preparation with an improved detection rate for polyps and adenomas in most patients who have had poor bowel cleansing at a previous colonoscopy. PMID- 22067189 TI - Single-port laparoscopic diverting sigmoid colostomy. AB - BACKGROUND: Single-port laparoscopic surgery has been described for various colorectal conditions. Here, we report the first 4 single-port laparoscopic sigmoid colostomies for fecal diversion. METHODS: A 1.5-cm-round incision was made on the skin at a previously marked colostomy site. A wound retractor was inserted and an access platform with four 5-mm trocars was attached to the wound retractor. The sigmoid colon was mobilized using electrocautery, laparoscopic scissors, or an advanced bipolar device. A standard Brooke colostomy was created through the initial skin incision. RESULTS: Four elective single-port laparoscopic diverting colostomies were performed. Indications included obstructing colon and rectal cancers and intractable Crohn's proctitis. The average operative time was 73 minutes (range, 53-105), and blood loss was minimal (<50 mL). There were no intraoperative complications. Three of 4 patients received oral analgesia, and one patient received patient-controlled intravenous analgesia postoperatively. The average time to passage of flatus was 1 day. Diet was advanced either on the day of surgery or on postoperative day 1. The length of hospital stay ranged from 0 to 15 days. CONCLUSION: Single-port laparoscopic sigmoid colostomy is an effective technique that allows full intra-abdominal visualization and colonic mobilization while eliminating the need for additional skin incisions other than the colostomy site itself. PMID- 22067190 TI - The long-term gastrointestinal functional outcomes following curative anterior resection in adults with rectal cancer: a systematic review and meta-analysis. AB - BACKGROUND: Significant variability and a lack of transparency exist in the reporting of anterior resection outcomes. OBJECTIVES: This study aimed to qualitatively analyze the long-term functional outcomes and assessment tools used in evaluating patients with rectal cancer following anterior resection, to quantify the incidence of these outcomes, and to identify risk factors for long term incontinence. DATA SOURCES: MEDLINE, Embase, and CINAHL were searched using the terms rectal neoplasms, resection, and gastrointestinal function. STUDY SELECTION: The studies included were in English and evaluated adults with rectal cancer, curative anterior resection, and a minimum 1-year follow-up. Patients with recurrent/metastatic disease were excluded. Of the 805 records identified, 48 articles were included. INTERVENTION: The intervention performed was anterior resection. MAIN OUTCOME MEASURES: The main outcome measure was incontinence (gas, liquid stool, and solid stool). RESULTS: The histories of 3349 patients from 17 countries were summarized. Surgeries were conducted between 1978 to 2004 with a median follow-up of 24 months (interquartile range, 12, 57). Sixty-five percent of studies did not use a validated assessment tool. Reported outcomes and incidence rates were variable. The reported proportion of patients with incontinence ranged from 3.2% to 79.3%, with a pooled incidence of 35.2% (95% CI 27.9, 43.3). Risk factors for incontinence, identified by meta-regression, were preoperative radiation 0.009 and, in particular, short-course radiation (P = .006), and study quality (randomized controlled trial P = .004, observational P = .006). LIMITATIONS: The meta-analysis was limited by the significant heterogeneity of the primary data. CONCLUSIONS: Functional outcomes are inconsistently assessed and reported and require common definitions, and the more regular use of validated assessment tools, as well. Preoperative radiation and, in particular, short-course radiation may be a strong risk factor for incontinence; however, further studies are needed. PMID- 22067195 TI - Plasmonic Mach-Zehnder interferometer for ultrasensitive on-chip biosensing. AB - We experimentally demonstrate a plasmonic Mach-Zehnder interferometer (MZI) integrated with a microfluidic chip for ultrasensitive optical biosensing. The MZI is formed by patterning two parallel nanoslits in a thin metal film, and the sensor monitors the phase difference, induced by surface biomolecular adsorptions, between surface plasmon waves propagating on top and bottom surfaces of the metal film. The combination of a nanoplasmonic architecture and sensitive interferometric techniques in this compact sensing platform yields enhanced refractive index sensitivities greater than 3500 nm/RIU and record high sensing figures of merit exceeding 200 in the visible region, greatly surpassing those of previous plasmonic sensors and still hold potential for further improvement through optimization of the device structure. We demonstrate real-time, label free, quantitative monitoring of streptavidin-biotin specific binding with high signal-to-noise ratio in this simple, ultrasensitive, and miniaturized plasmonic biosensor. PMID- 22067196 TI - Plasma and cerebrospinal fluid pharmacokinetics of naproxen in children. AB - The aim of this study was to characterize pediatric pharmacokinetics and central nervous system exposure of naproxen after oral administration. The pharmacokinetics of naproxen was studied in 53 healthy children aged 3 months to 12 years undergoing surgery with spinal anesthesia. Children received preoperatively a single dose of 10 mg/kg oral naproxen suspension. A single cerebrospinal fluid (CSF) sample (n = 52) was collected at the induction of anesthesia, and plasma samples (n = 270) were collected before, during, and after the operation (up to 51 hours after administration). A population pharmacokinetic model was built using the NONMEM software. Naproxen concentrations in plasma were well described by a 2-compartment model. The estimated oral clearance (CL/F) was 0.62 L/h when linearly scaled by weight to 70 kg. The apparent volume of distribution at steady state (Vss/F) was 12.5 L /70 kg. The findings are consistent with previously reported pharmacokinetic parameters for children older than 5 years. Naproxen permeated into the CSF and reached CSF concentrations that were 4 times higher than unbound plasma concentrations. Based on these data, weight can be used as a basis for naproxen dosing in children older than 3 months of age. PMID- 22067197 TI - Shortening of the QT interval after food can be used to demonstrate assay sensitivity in thorough QT studies. AB - The effect of food was investigated under conditions of a thorough QT (TQT) study and with confirmation of assay sensitivity by the use of a positive control (400 mg of moxifloxacin). Fifty-five healthy subjects were randomized to treatment and a sequence of fasted and fed baseline electrocardiography days. Subjects received standard breakfast 30 to 10 minutes prior to dosing. Measurement of QT interval was performed automatically with subsequent manual onscreen overreading using electronic calipers. A profound increase in heart rate of 9.4 bpm was observed in the fed condition compared with the fasted condition at 1.5 hours after dose with a corresponding shortening of QT (27 milliseconds); (baseline data). When corrected, QTcF interval was shortened significantly with the maximal effect observed at 2 hours after dose of 8.2 (95% confidence interval, 6-10) milliseconds. A concurrent shortening of the PR interval with a maximum value of 5.6 milliseconds was also observed. The findings of this study demonstrate that food alters the QT-RR relationship and shortens QTc and PR for at least 4 hours after a carbohydrate-rich meal. The findings are of regulatory interest as this study shows that normal physiological causes can shorten QTc significantly and that it could be used as a method to demonstrate assay sensitivity. PMID- 22067198 TI - Smoking and risk of incident psoriatic arthritis in US women. AB - OBJECTIVES: Psoriatic arthritis (PsA) is an inflammatory arthritis that is associated with psoriasis. Previous studies have found an association between smoking and psoriasis, but the association with PsA is unclear. The authors aimed to evaluate the association between smoking and the risk of incident PsA in a large cohort of women. METHODS: 94 874 participants were included from the Nurses' Health Study II over a 14-year period (1991-2005). Information on smoking was collected biennially during follow-up. The incidence of clinician-diagnosed PsA was ascertained and confirmed by self-reported questionnaires. RESULTS: During 1 303 970 person-years' follow-up, the authors identified 157 incident PsA cases. Among total participants, smoking was associated with an elevated risk of incident PsA. Compared with never smokers, the RR was 1.54 for past smokers (95% CI 1.06 to 2.24) and 3.13 for current smokers (95% CI 2.08 to 4.71). With increasing smoking duration or pack-years, the risk of PsA increased monotonically (p for trend <0.0001). The increase in risk was particularly significant for PsA cases with more severe phenotypes. Secondary analysis among participants developing psoriasis during the follow-up replicated the association, demonstrating an increased risk of PsA among psoriasis cases. The risk was significant for those with higher cumulative measures of smoking or PsA cases with more severe phenotypes. CONCLUSION: In this study smoking was found to be associated with a risk of PsA and cumulative measures of smoking were also associated with a higher risk of PsA among women. PMID- 22067199 TI - Association of osteonecrosis and peripheral neuropathy in HIV-1-infected patients: possible roles of nerve growth factor and vascular endothelial growth factor. PMID- 22067200 TI - Sustained virological response to a raltegravir-containing salvage therapy in an HIV-2-infected patient. PMID- 22067201 TI - The price of tenofovir-emtricitabine undermines the cost-effectiveness and advancement of pre-exposure prophylaxis. PMID- 22067202 TI - Synthesis and characterization of novel 2, 2'-bipyrimidine fluorescent derivative for protein binding. AB - BACKGROUND: Fluorescent dyes with biocompatible functional group and good fluorescence behavior are used as biosensor for monitoring different biological processes as well as detection of protein assay. All reported fluorophore used as sensors are having high selectivity and sensitivity but till there is more demand to synthesized new fluorophore which have improved fluorescence properties and good biocompatibility. RESULTS: Novel 4, 4'-(1, 1'-(5-(2-methoxyphenoxy)-[2, 2' bipyrimidine]-4, 6-diyl)bis(1H-pyrazol-3, 1-diyl)) dianiline fluorescent dye was synthesized by multistep synthesis from 2-phenylacetonitrile, 2-chloropyrimidine and 2-methoxyphenol. This dye has absorption at 379 nm with intense single emission at 497 nm having fairly good quantum yield (0.375) and Stokes shift. The intermediates and dye were characterized by FT-IR, 1H NMR, 13C NMR and Mass spectral analysis. The pyrazole bipyrimidine based fluorescent dye possessing two amino groups suitable for binding with protein is reported. Its utility as a biocompatible conjugate was explained by conjugation with bovine serum albumin. The method is based on direct fluorescence detection of fluorophore-labelled protein before and after conjugation. Purified fluorescent conjugate was subsequently analyzed by fluorimetry. The analysis showed that the tested conjugation reaction yielded fluorescent conjugates of the dye through carbodiimide chemistry. CONCLUSION: In summery synthesized fluorophore pyrazole bipyrimidine has very good interaction towards protein bovine serum albumin and it acts as good candidate for protein assay. PMID- 22067204 TI - Learning curve and surgical outcome for single-port access total laparoscopic hysterectomy in 100 consecutive cases. AB - AIMS: To define the learning curve for single-port access (SPA) total laparoscopic hysterectomy (TLH) and evaluate the surgical outcomes. METHODS: Patient demographics and segmental operating times of all 100 patients who underwent SPA-TLH by a single surgeon were analyzed. Patients were arranged in order based on surgery date. RESULTS: 100 patients underwent SPA-TLH. There was no conversion to conventional laparoscopy or laparotomy. The median time until the removal of a specimen (T(R)) was 45 min and the median time for closure of the vaginal cuff (T(C)) was 18 min. The median total operating time from skin opening to closure (T(O)) was 80 min. T(R), T(C), and T(O) decreased significantly over the study period. The T(C) decreased significantly from the first 20 cases to the next 20 (p = 0.028) and the T(O) from the second 20 cases to the next 20 (p = 0.029). CONCLUSIONS: Proficiency for SPA-TLH was achieved after 40 cases. Operating time and postoperative hemoglobin drop decreased with experience, without increasing complication. PMID- 22067203 TI - Isolation of protein-tyrosine phosphatase-like member-a variant from cementum. AB - Cementum has been shown to contain unique polypeptides that participate in cell recruitment and differentiation during cementum formation. We report the isolation of a cDNA variant for protein-tyrosine phosphatase-like (proline instead of catalytic arginine) member-a (PTPLA) from cementum. A cementifying fibroma-derived lambda-ZAP expression library was screened by panning with a monoclonal antibody to cementum attachment protein (CAP), and 1435 bp cDNA (gb AC093525.3) was isolated. This cDNA encodes a 140-amino-acid polypeptide, and its N-terminal 125 amino acids are identical to those of PTPLA. This isoform, designated as PTPLA-CAP, results from a read-through of the PTPLA exon 2 splice donor site, truncating after the second putative transmembrane domain. It contains 15 amino acids encoded within the intron between PTPLA exons 2 and 3, which replace the active site for PTPLA phosphatase activity. The recombinant protein, rhPTPLA-CAP, has Mr 19 kDa and cross-reacts with anti-CAP antibody. Anti rhPTPLA-CAP antibody immunostained cementum cells, cementum, heart, and liver. Quantitative RT-PCR showed that PTPLA was expressed in all periodontal cells; however, PTPLA-CAP expression was limited to cementum cells. The rhPTPLA-CAP promoted gingival fibroblast attachment. We conclude that PTPLA-CAP is a splice variant of PTPLA, and that, in the periodontium, cementum and cementum cells express this variant. PMID- 22067205 TI - Mean displacement map of spine and spinal cord disorders using high b-value q space imaging-feasibility study. AB - BACKGROUND: Q-space analysis is a new metric that uses multiple, high b-value, diffusion-weighted magnetic resonance (MR) data. This technique shows promising results as a tool to provide information complementary to that of other imaging techniques used on biological tissue in vivo. PURPOSE: To investigate the use of a mean displacement (MDP) map of high b-value, q-space imaging (QSI) to characterize spinal and spinal cord lesions in vivo. MATERIAL AND METHODS: Eight patients with spine or spinal cord disorders (two neurinomas, one myeloma, three cases of syringohydromyelia, and two cases of cervical spondylosis) were included. The MR imaging protocol consisted of conventional MR sequences, conventional diffusion-weighted imaging (DWI; b = 1000), and high b-value QSI with a maximum q value of 836.9 cm(-1). Apparent diffusion coefficient (ADC) maps of conventional DWI and MDP maps of QSI data were obtained and region-of-interest analyses for the lesions were performed. RESULTS: MDP values of normal spinal cord, cerebrospinal fluid (CSF), and tumor parenchyma were 6.57 +/- 0.52, 17.6 +/ 2.75, and 8.49 +/- 2.09, respectively (um, mean +/- standard deviation). In general, MDP maps were not well correlated with the corresponding ADC maps at the pathologic lesions. Spondylotic lesions tended to have higher MDP values than normal spinal cord, whereas syringohydromyelia produced MDP values slightly lower than those of CSF. CONCLUSION: The heterogeneous MDP values were probably due to differences in tissues and pathologic structures. This technique has potential to provide additional clinical information to that obtained with conventional MR imaging. PMID- 22067206 TI - FDG-PET/CT in the diagnosis of recurrent breast cancer. AB - BACKGROUND: An advantage of PET/CT has been demonstrated for diagnosis of several tumor entities. In patients with breast cancer, early diagnosis and accurate restaging of recurrence after surgery is important for selection of the most appropriate therapeutic strategy. Purpose To evaluate the accuracy of integrated positron emission tomography and computed tomography (PET/CT) using 18F fluorodeoxyglucose (FDG), for follow-up of patients with suspected recurrent breast cancer. MATERIAL AND METHODS: Forty-seven patients with suspected recurrent breast cancer underwent PET/CT. The PET and PET/CT images were interpreted without knowledge of the results of other diagnostic modalities, and compared with each other with reference to the final diagnosis. RESULTS: Twenty five (53%) patients suffered tumor recurrence. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 96%, 91%, 92%, 95%, and 94%, respectively. In comparison with PET, PET/CT had a higher sensitivity and accuracy (96% vs. 80% and 94% vs. 81%, respectively). The difference in diagnostic accuracy between PET/CT and PET was significant (P < 0.05). CONCLUSION: The present findings indicate that PET/CT is an accurate, sensitive and reliable modality for screening and detection of breast cancer recurrence. PET/CT appears to be an effective surveillance tool, as it is able to cover the whole body in a single procedure and shows good performance. PMID- 22067207 TI - Main bronchial diverticula in the subcarinal region: their relation to airflow limitations. AB - BACKGROUND: To date, bronchial diverticula have generally been treated as a pathological condition associated with chronic obstructive pulmonary disease (COPD), although only a limited amount of published information is available on the relationship between bronchial diverticula as depicted by multidetector computed tomography (MDCT) and airflow limitations. PURPOSE: To evaluate the relationship between airflow limitations and main bronchial diverticula in the subcarinal region using spirometry and thin-section MDCT. MATERIAL AND METHODS: A total of 189 consecutive adult patients were retrospectively evaluated based on spirometry and thin-section MDCT of the chest. All examinations were performed at our institution between June and October 2008. The study group included 70 women and 119 men with a mean age of 65 years (range 19-86 years). The relationship between the FEV(1)% and bronchial diverticula in the subcarinal region was analyzed (Student's t-test). RESULTS: The indications for conducting the examinations were pulmonary diseases (82 patients), cardiovascular diseases (22), extrapulmonary malignancies (74), and other conditions (11). A total of 84/189 (44.4%) patients showed bronchial diverticula, and the FEV(1)% of 70/84 (83.3%) patients was above 70. The FEV(1)% of patients with lesions ranged from 26.0 to 97.8 (mean 76.8), whereas the range was 28.1-94.4 (mean 73.7) in those without lesions. There was no significant association between the FEV(1)% and the presence of subcarinal bronchial diverticula (P > 0.05). CONCLUSION: Our data demonstrate that thin-section chest CT commonly demonstrates main bronchial diverticula in the subcarinal region in patients without airflow limitations. We propose that the presence of a small number of tiny bronchial diverticula under the carina may not be a criterion for the diagnosis of COPD. PMID- 22067208 TI - Stent-graft placement for urgent treatment or prevention of bleeding. AB - BACKGROUND: Stent-graft treatment of the patients with ongoing bleeding may be beneficial in specific situations, especially when preservation of blood flow to the distant organs is important. PURPOSE: To present the results of stent-graft placement for urgent treatment or prevention of the bleeding. MATERIAL AND METHODS: Stent-graft placement was performed urgently for the treatment of active bleeding and/or pseudoaneurysm/aneurysm in 17 patients. Diagnoses were based on clinical findings and/or imaging studies. The etiology was previous major surgery and/or percutaneous intervention in 13, malignancy in one, pancreatitis and pseudocyst in one, multitrauma due to traffic accident in one and unknown cause in one patient. RESULTS: A total of 23 stent-grafts were placed. Angiograms obtained after placement revealed patent stent-graft with no further active extravasation or filling of pseudoaneurysm in 14 patients. Due to persistent bleeding, embolization was performed in two patients. In three patients, the stent-grafts were found to be thrombosed either immediately after placement (n = 1) or at follow-up (n = 2). Stent-grafts were patent in six of nine patients that could be followed (between 3 months and 6 years). CONCLUSION: Urgent stent-graft placement may be an alternative to endovascular embolization or surgery. It may be preferred when embolization is technically difficult or impossible and/or when preservation of blood supply to distal organs is essential such as in liver transplant grafts or extremity salvage. PMID- 22067209 TI - Vahlkampfia sp: structural observations of cultured trophozoites. AB - Some structural observations on cultured Vahlkampfia sp. trophozoites are reported. Trophozoites are active and pleomorphic, producing large cell protrusions related to locomotion such as lamellipodia, filopodia and endocytic structures formed by hyaline cytoplasm, in which actin provides a framework that allows rapid changes in morphology. As observed by transmission electron microscopy, the cytoplasm is highly granular masking some cell organelles and the major cytoplasmic membrane systems. The structure of cell organelles such as the nucleus, endoplasmic reticulum, and digestive vacuoles is described. A common finding was the presence of 50 nm electron-dense round granules that are not limited by a membrane and that appear scattered in the cytoplasm, and whose function remains unknown. Apparently, the cell reserve material is glycogen, since complete trophozoites were positive to Schiff periodic-acid technique. PMID- 22067210 TI - Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory. AB - It has been shown that the brain has its own intrinsic renin-angiotensin system (RAS) and angiotensin-(1-7) (Ang-(1-7)) is particularly interesting, because it appears to counterbalance most of the Ang II effects. Ang-(1-7) exerts its biological function through activation of the G-protein-coupled receptor Mas. Interestingly, hippocampus is one of the regions with higher expression of Mas. However, the role of Ang-(1-7)/Mas axis in hippocampus-dependent memories is still poorly understood. Here we demonstrated that Mas ablation, as well as the blockade of Mas in the CA1-hippocampus, impaired object recognition memory (ORM). We also demonstrated that the blockade of Ang II receptors AT1, but not AT2, recovers ORM impairment of Mas-deficient mice. Considering that high concentrations of Ang-(1-7) may activate AT1 receptors, nonspecifically, we evaluate the levels of Ang-(1-7) and its main precursors Ang I and Ang II in the hippocampus of Mas-deficient mice. The Ang I and Ang II levels are unaltered in the whole hipocampus of MasKo. However, Ang-(1-7) concentration is increased in the whole hippocampus of MasKo mice, as well as in the CA1 area. Taken together, our findings suggest that the functionality of the Ang-(1-7)/Mas axis is essential for normal ORM processing. PMID- 22067211 TI - Effects of anticipation certainty on preparatory brain activity and anticipatory postural adjustments associated with voluntary unilateral arm movement while standing. AB - We examined the effects of anticipation certainty concerning which voluntary movement is required in response to a stimulus while standing on preparatory brain activity and anticipatory postural adjustments (APAs). Ten right-handed adults abducted their left or right arm rapidly in response to a visual imperative stimulus, based on the type of stimulus. A warning cue, which did or did not contain information about the side of arm abduction, was presented 2000ms before the imperative stimulus. Preparatory brain activity before arm abduction was quantified by the mean amplitude of the contingent negative variation 100ms before the imperative stimulus (late CNV amplitude). Compared with the low anticipation condition, in the high anticipation condition the following results were obtained only in the case of right arm abduction: (1) larger late CNV amplitude, (2) earlier postural muscle activities with respect to the focal muscle of arm abduction, and (3) smaller peak displacement of center of pressure during the abduction. These findings suggest that high anticipation of voluntary movement of dominant arm to a stimulus while standing influences preparatory brain activity before the movement, resulting in earlier APAs and thus smaller disturbance of postural equilibrium during the movement. PMID- 22067212 TI - Population variation in NAIP functional copy number confers increased cell death upon Legionella pneumophila infection. AB - The NAIP gene encodes an intracellular innate immunity receptor that senses flagellin. The genomic region containing NAIP presents a complex genomic organization and includes various NAIP paralogs. Here, we assessed the degree of copy number variation of the complete NAIP gene (NAIPFull) in various human populations and studied the functional impact of such variation on host cell fate using Legionella pneumophila as an infection model. We determined that African populations have a NAIPFull duplication at a higher frequency than Europeans and Asians, with an increased transcription of the gene. In addition, we demonstrated that a higher amount of the NAIPFull protein dramatically increases cell death upon infection by L. pneumophila, a mechanism that may account for increased host resistance to infection. We postulate that the NAIPFull gene duplication might have been evolutionary maintained, or even selected for, because it may confer an advantage to the host against flagellated bacteria. PMID- 22067213 TI - Measuring capacity building in communities: a review of the literature. AB - BACKGROUND: Although communities have long been exhorted to make efforts to enhance their own health, such approaches have often floundered and resulted in little or no health benefits when the capacity of the community has not been adequately strengthened. Thus being able to assess the capacity building process is paramount in facilitating action in communities for social and health improvement. The current review aims to i) identify all domains used in systematically documented frameworks developed by other authors to assess community capacity building; and ii) to identify the dimensions and attributes of each of the domains as ascribed by these authors and reassemble them into a comprehensive compilation. METHODS: Relevant published articles were identified through systematic electronic searches of selected databases and the examination of the bibliographies of retrieved articles. Studies assessing capacity building or community development or community participation were selected and assessed for methodological quality, and quality in relation to the development and application of domains which were identified as constituents of community capacity building. Data extraction and analysis were undertaken using a realist synthesis approach. RESULTS: Eighteen articles met the criteria for this review. The various domains to assess community capacity building were identified and reassembled into nine comprehensive domains: "learning opportunities and skills development", "resource mobilization", "partnership/linkages/networking", "leadership", "participatory decision-making", "assets-based approach", "sense of community", "communication", and "development pathway". Six sub-domains were also identified: "shared vision and clear goals", "community needs assessment", "process and outcome monitoring", "sustainability", "commitment to action" and "dissemination". CONCLUSIONS: The set of domains compiled in this review serve as a foundation for community-based work by those in the field seeking to support and nurture the development of competent communities. Further research is required to examine the robustness of capacity domains over time and to examine capacity development in association with health or other social outcomes. PMID- 22067214 TI - Hypertrophic cardiomyopathy in a neonate associated with nemaline myopathy. AB - Nemaline myopathy is a congenital nonprogressive skeletal muscle disorder with a characteristic rod body formation in the skeletal muscle fibers. Cardiac involvement in nemaline myopathy is rare, although both dilated and hypertrophic cardiomyopathy have been reported. We describe an infant diagnosed with hypertrophic cardiomyopathy and hypotonia on the first day of life. Muscle biopsy confirmed nemaline myopathy at 3 weeks of age. The diagnosis of nemaline myopathy precluded consideration of heart transplantation, thus shifting the focus to comfort care. This is the earliest presentation of hypertrophic cardiomyopathy reported in the literature in the setting of nemaline myopathy. The approach to determining an etiology for hypertrophic cardiomyopathy in an infant is reviewed. PMID- 22067215 TI - First report of the protective effects of remote per- and postconditioning on ischemia/reperfusion-induced renal injury. PMID- 22067216 TI - Sitagliptin therapy in kidney transplant recipients with new-onset diabetes after transplantation. PMID- 22067217 TI - Accelerated kidney transplant rejection and hypertensive encephalopathy in a pediatric patient associated with antibodies against angiotensin type 1 receptor and HLA class II. PMID- 22067218 TI - Successful splenic venous drainage for kidney transplant in case of inferior vena cava thrombosis. PMID- 22067219 TI - Letter referring to the paper by Galinovic et al.: fully automated postprocessing carries a risk of substantial overestimation of perfusion deficits in acute stroke magnetic resonance imaging. PMID- 22067220 TI - Multi-detector computed tomography demonstration of double-lumen aortic arch- persistent fifth arch--as an isolated anomaly in an adult. AB - Persistent fifth - double-lumen - aortic arch is a rarely seen entity, which is usually associated with other cardiac anomalies; it has been previously reported only in children. We report a new case of double-lumen aortic arch with a systemic-to-systemic connection diagnosed incidentally during cardiac multi detector computer tomography evaluation of coronary artery bypass grafts in an adult. PMID- 22067221 TI - Creutzfeldt-Jakob disease surveillance in Argentina, 1997-2008. AB - BACKGROUND: Epidemiological data on Creutzfeldt-Jakob disease (CJD) from Latin America are limited. We present a comprehensive epidemiological survey on CJD patients in Argentina based on systematic surveillance between 1997 and 2008. METHODS: A CJD Surveillance Referral Center (SRC) was established in Argentina in 1997; previously a Neuropathology Referral Center was used from 1983 to 1996. All suspected cases referred to the SRC were classified using established criteria on the basis of information derived from the following: clinical data form, EEG, MRI (both for central review), cerebrospinal fluid (CSF) for protein 14-3-3 Western blot (WB), autopsy or biopsy material for neuropathology, prion protein (PrP) immunohistochemistry and PrP WB, as well as blood for DNA studies (when brain tissue was not available). RESULTS: Of the 517 patients referred to the SRC between 1997 and 2008, 211 (40.8%) had CJD or other transmissible spongiform encephalopathies (TSEs) (definite or probable). Possible cases totaled 14.5%, while cases with no WHO criteria accounted for 16.4%. Non-CJD cases excluded by biopsy/autopsy or during follow-up corresponded to 28.2% of the 517 referrals. Main differential diagnoses included neurodegenerative diseases such as Alzheimer's disease, frontotemporal dementia, vascular, metabolic or viral encephalopathy, and Hashimoto's disease. Five percent of referred patients ultimately recovered. Eighty-three percent of TSE cases were sporadic CJD; 17% were genetic, mainly E200K (15.6%); the remaining 1.4% included an octarepeat insertion and two Gerstmann-Straussler-Scheinker cases (P102L). Seventy-four of 100 definite cases had frozen tissue available for molecular subtyping (PrP(Sc)/codon 129). CSF protein 14-3-3 WB sensitivity was 72.3% and specificity was 92.1%. Clinical diagnostic criteria for probable CJD when compared to definite diagnosis by neuropathology showed 71.3% sensitivity, 86.2% specificity, 94.4% positive predictive value and 48% negative predictive value. Country incidence increased over time and reached 0.85 cases per million in 2008, with the highest rate detected in the city of Buenos Aires (1.8). Districts with 6% of the total population have never reported suspected cases. CONCLUSION: In spite of an increase in incidence observed over time, the difference between Buenos Aires city, where the incidence is comparable to that of smaller European countries with higher population density, and the incidence observed in the rest of the country suggests underreporting in nonmetropolitan areas, probably due to a lack of access to specialized medical facilities. CSF WB sensitivity results for protein 14-3-3 were probably linked to the fact that testing was not routinely repeated during the course of the disease, when earlier test results had been negative. The spectrum of molecular CJD subtypes observed did not differ from other countries in Europe. No iatrogenic or variant CJD cases were identified. The sensitivity and negative predictive value of clinical diagnostic criteria for probable CJD (which includes EEG and/or CSF protein 14-3-3 levels) may have been resulted from confirmed cases not meeting probable criteria before autopsy, due to a lack of ancillary tests such as EEG and/or CSF 14-3-3 WB, or because negative tests were not repeated during follow-up. PMID- 22067222 TI - Back to the future: the changing frontiers of nutrition research and its relationship to policy. AB - Seventy years have elapsed since the Nutrition Society was founded and John Boyd Orr became its first Chairman. Over the intervening period, nutrition research has embraced and responded to a wide variety of challenges as the requirements of research have evolved and changed. This paper reflects on some of the major challenges that have influenced nutrition research over the past 70 years and considers where nutrition stands today along with the challenges for the future. In the past, these challenges have included food security and improvements in animal nutrition to enhance production through problems of overnutrition, such as CVD and obesity, as well as the recognition of the importance of early-life nutrition. The challenges for the future include how to translate the increasingly comprehensive and complex understanding of the relationship between nutrition and health, being gained as a result of the genomic revolution, into simple and accessible policy advice. It also includes how we learn more about the ways in which diet can help in the prevention of obesity as well as the ways in which we prevent the rise in complex diseases in emerging nations as they undergo nutritional transition. From this, it is clear that nutrition research has moved a long way from its initial focus on nutritional deficiencies to a subject, which is at the heart of public health consideration. This evolution of nutrition research means that today diet and health are high on the political agenda and that nutrition remains a priority area for research. It has been 70 years since 1941 when the Nutrition Society was established, under its first Chairman, John Boyd Orr. At that time there were many who believed that nutrition research had reached its peak and there was little left to discover. This view stemmed from the fact that most vitamins and minerals had been discovered and that the syndromes associated with nutritional deficiencies in these were largely known. Despite this gloomy prognosis, the intervening 70 years have witnessed a remarkable evolution in nutrition research, which has underpinned key Government policies, ranging from food security right through to public health. This review considers some major developments that have helped to shape nutrition research over the past 70 years and in so doing have changed its frontiers. PMID- 22067223 TI - Effect of ghrelin on protein kinase C-epsilon and protein kinase C-delta gene expression in the pulmonary arterial smooth muscles of chronic hypoxic rats. AB - INTRODUCTION: Protein kinase C (PKC), can be activated in pulmonary arterial smooth muscle cells during hypoxia, leading to hypoxic pulmonary vasoconstriction (HPV). Studies are going on to detect the strict PKC isoform involved in the phenomenon. It has been shown that ghrelin, a 28-amino-acid peptide, may protect lungs from HPV side effects, to some extent. The aim of study was to evaluate the effect of exogenous ghrelin on PKC-epsilon and PKC-delta gene expression during chronic hypoxia. MATERIAL AND METHODS: Twenty-four adult male Wistar rats were divided randomly in 3 groups. Hypoxic rats with saline or ghrelin treatment were placed in a normobaric hypoxic chamber for 2 weeks. Controls remained in room air. PKC-epsilon and PKC-delta gene expression was measured by real-time RT-PCR. RESULTS: Morphometric analysis showed that ghrelin reversed the hypoxia induced pulmonary artery wall thickness. In hypoxic animals, there was a 2- and 4-fold increment in PKC-epsilon and PKC- delta gene expression, respectively. Ghrelin treatment reduced the overexpression of PKC-epsilon and PKC-delta to control animals' value. CONCLUSION: Ghrelin by decreasing the expression of PKC-epsilon and PKC-delta in hypoxic animals reduces the HPV. Although more studies are needed, it could be an honest deduction that ghrelin affects HPV in a multifunctional manner and might be used as a therapeutic agent in the future. PMID- 22067225 TI - Correlates of male fitness in captive zebra finches--a comparison of methods to disentangle genetic and environmental effects. AB - BACKGROUND: It is a common observation in evolutionary studies that larger, more ornamented or earlier breeding individuals have higher fitness, but that body size, ornamentation or breeding time does not change despite of sometimes substantial heritability for these traits. A possible explanation for this is that these traits do not causally affect fitness, but rather happen to be indirectly correlated with fitness via unmeasured non-heritable aspects of condition (e.g. undernourished offspring grow small and have low fitness as adults due to poor health). Whether this explanation applies to a specific case can be examined by decomposing the covariance between trait and fitness into its genetic and environmental components using pedigree-based animal models. We here examine different methods of doing this for a captive zebra finch population where male fitness was measured in communal aviaries in relation to three phenotypic traits (tarsus length, beak colour and song rate). RESULTS: Our case study illustrates how methods that regress fitness over breeding values for phenotypic traits yield biased estimates as well as anti-conservative standard errors. Hence, it is necessary to estimate the genetic and environmental covariances between trait and fitness directly from a bivariate model. This method, however, is very demanding in terms of sample sizes. In our study parameter estimates of selection gradients for tarsus were consistent with the hypothesis of environmentally induced bias (betaA=0.035+/-0.25 (SE), betaE=0.57+/ 0.28 (SE)), yet this differences between genetic and environmental selection gradients falls short of statistical significance. CONCLUSIONS: To examine the generality of the idea that phenotypic selection gradients for certain traits (like size) are consistently upwardly biased by environmental covariance a meta analysis across study systems will be needed. PMID- 22067226 TI - Local morphology fitting active contour for automatic vascular segmentation. AB - In this paper, we propose an active contour model using local morphology fitting for automatic vascular segmentation on 2-D angiogram. The vessel and background are fitted to fuzzy morphology maximum and minimum opening, separately, using linear structuring element with adaptive scale and orientation. The minimization of the energy associated with the active contour model is implemented within a level set framework. As in the current local model, fitting the image to local region information makes the model robust against the inhomogeneous background. Moreover, selective local estimations for fitting that are precomputed instead of updated in each contour evolution makes the evolution of level set robust again initial location compared to the current local model. The results on synthetic image and real angiogram compared with other methods are presented. It is shown that the proposed method can achieve automatic and accurate segmentation of vascular angiogram. PMID- 22067224 TI - Identification, characterization, and comparative genomic distribution of the HERV-K (HML-2) group of human endogenous retroviruses. AB - BACKGROUND: Integration of retroviral DNA into a germ cell may lead to a provirus that is transmitted vertically to that host's offspring as an endogenous retrovirus (ERV). In humans, ERVs (HERVs) comprise about 8% of the genome, the vast majority of which are truncated and/or highly mutated and no longer encode functional genes. The most recently active retroviruses that integrated into the human germ line are members of the Betaretrovirus-like HERV-K (HML-2) group, many of which contain intact open reading frames (ORFs) in some or all genes, sometimes encoding functional proteins that are expressed in various tissues. Interestingly, this expression is upregulated in many tumors ranging from breast and ovarian tissues to lymphomas and melanomas, as well as schizophrenia, rheumatoid arthritis, and other disorders. RESULTS: No study to date has characterized all HML-2 elements in the genome, an essential step towards determining a possible functional role of HML-2 expression in disease. We present here the most comprehensive and accurate catalog of all full-length and partial HML-2 proviruses, as well as solo LTR elements, within the published human genome to date. Furthermore, we provide evidence for preferential maintenance of proviruses and solo LTR elements on gene-rich chromosomes of the human genome and in proximity to gene regions. CONCLUSIONS: Our analysis has found and corrected several errors in the annotation of HML-2 elements in the human genome, including mislabeling of a newly identified group called HML-11. HML-elements have been implicated in a wide array of diseases, and characterization of these elements will play a fundamental role to understand the relationship between endogenous retrovirus expression and disease. PMID- 22067227 TI - Ligand-controlled rates of photoinduced electron transfer in hybrid CdSe nanocrystal/poly(viologen) films. AB - This paper describes a study of the rates of photoinduced electron transfer (PET) from CdSe quantum dots (QDs) to poly(viologen) within thin films, as a function of the length of the ligands passivating the QDs. Ultrafast (<10 ps), quantitative PET occurs from CdSe QDs coated with HS-(CH(2))(n)-COOH for n = 1, 2, 5, and 7 to viologen units. The observed decrease in the magnitude of the PET rate constant with n is weaker than that expected from the decay of the electron tunneling probability across extended all-trans mercaptocarboxylic acids but well described by electron tunneling across a collapsed ligand shell. The PET rate constants for films with n = 10 and 15 are much slower than those expected based on the trend for n = 1-7; this deviation is ascribed to the formation of bundles of ligands on the surface of the QD that make the tunneling process prohibitively slow by limiting access of the viologen units to the surfaces of the QDs. This study highlights the importance of molecular-level morphology of donor and acceptor materials in determining the rate and yield of interfacial photoinduced electron transfer in thin films. PMID- 22067228 TI - From the editor: re-form: inside and outside perspectives on health care. PMID- 22067229 TI - Knowledge for re-forming nursing's future: standpoint makes a difference. AB - We draw on our recent research that has convinced us of the importance of nurses' participating in re-forming health care on their own terms. The empirical evidence we present here shows how "boardroom knowledge" of health care is constructed with different priorities than is the knowledge of direct care on which nurses' safe, efficient, and effective work relies. The 2 forms of knowledge are not the same. Nurses' knowledge is routinely transposed through a procrustean process of "working up" direct care nurses' knowledge into new informational forms without attention to the importance of the full range of what nurses know from their unique standpoint. PMID- 22067230 TI - Instrumental care and human-centered caring: rhetoric and lived reality. AB - This article explores the nursing discourse on relational caring as a context for examining the authors' recent lived realities with the health care system. Two narratives detail experiences of instrumental care and human-centered caring as the authors journeyed with a loved one who was dying. Commonalities across the stories are identified and caring analyzed using Halldorsdottir's ways of being with another. From weaving an analysis of the realities with the literature emerges a recognition of a critical turning point in nursing and health care. PMID- 22067231 TI - Critical interactionism: an upstream-downstream approach to health care reform. AB - Currently, per capita health care expenditures in the United States are more than 20% higher than any other country in the world and more than twice the average expenditure for European countries, yet the United States ranks 37th in life expectancy. Clearly, the health care system is not succeeding in improving the health of the US population with its focus on illness care for individuals. A new theoretical approach, critical interactionism, combines symbolic interactionism and critical social theory to provide a guide for addressing health care problems from both an upstream and downstream approach. Concepts of meaning from symbolic interactionism and emancipation from critical perspective move across system levels to inform and reform health care for individuals, organizations, and societies. This provides a powerful approach for health care reform, moving back and forth between the micro and macro levels. Areas of application to nursing practice with several examples (patients with obesity; patients who are lesbian, gay, bisexual, and transgender; workplace bullying and errors), nursing education, and research are also discussed. PMID- 22067232 TI - Accounting for care: exploring tensions and contradictions. AB - Within the context of neoliberal restructuring, accountability is primarily linked to efficiency, determined through standardized, numerically based technologies and focused on lengths of stay, utilization indicators, and the like. Disappearing from view in this approach is what is actually happening at the point of care for registered nurses. Grounded in semistructured interviews, this article casts a critical light on the tensions and contradictions experienced by nurses, arguing that instead of a more accountable, effective, or efficient system, this path is jeopardizing nurses' ability to provide needed care within healthy, supportive work environments, setting into motion a fundamental transformation of nursing practice. PMID- 22067233 TI - "I will not be discriminated against": older lesbians creating new communities. AB - Lesbian, gay, bisexual, and transgender (LGBT) older adults fear discrimination in long-term care and voice a preference for LGBT-specific services. The purpose of this study was to describe, through the eyes of 10 socially interconnected older lesbians (>55 years), the roles that life experiences, social ties, and expectations for aging play in their decision to live in an LGBT continuous-care setting. Nursing has been largely inattentive to older lesbians' unique health and care issues. Reforms in nursing research, education, and practice are suggested to make this population more visible and better understood. PMID- 22067234 TI - Advancing population-based health-promotion and prevention practice in community health nursing: key conditions for change. AB - Community-health nursing practice is a pivotal aspect of present-day health reforms. In Quebec, Canada, the recent introduction of a population-based approach has entailed increasing the resources allocated to health promotion and disease prevention. Semistructured interviews were conducted with nurses and managers (N = 69) in an effort to understand how these new resources are reflected in nursing practice. Three classes of factors emerged as key conditions for change: contextual and historical, training and professional-development, and work-organization factors. The authors propose courses of action respecting these conditions to provide support for community-health nursing practices that incorporate a contemporary population-based approach. PMID- 22067235 TI - Of courage and leaving safe harbors. AB - If the health care system in the United States is to be sustainable, dramatic changes that result in better outcomes, lower costs, and improved quality are needed. As the largest group of health care providers, successful change will depend, in part, upon nursing practitioners, leaders, visionaries, advocates, and educators who are courageous enough to make difficult decisions and to follow through with actions. This philosophical inquiry addresses the nature of courage, types and motivations for courageous actions, and the complex psychological manifestations of thinking courageously. The inquiry concludes with educational and practical goals to promote proper use of courage in clinical practice. PMID- 22067236 TI - Delivering specialized palliative care in the community: a new role for nurse practitioners. AB - The rising population of older Americans with advanced illness challenges current care delivery models. We use the metaphor of advanced illness as a difficult journey and propose a specific role, that of the "OACIS NP [nurse practitioner]," who helps provide a place of refuge during this journey. "OACIS" is an acronym for Optimizing Advanced Complex Illness Support, a program to provide home-based palliative medical care. The 4 pillars of this collaborative model for advanced nursing care include care coordination, medical management, psychosocial support, and education. We make the case for this expanded role for nurse practitioners who specialize in palliative care. PMID- 22067237 TI - Effect of motivational music on lactate levels during recovery from intense exercise. AB - The effects of music played during an exercise task on athletic performance have been previously studied. Yet, these results are not applicable for competitive athletes, who can use music only during warm-up or recovery from exercise. Therefore, the aim of this study was to determine the effect of motivational music (music that stimulates or inspires physical activity) during recovery from intense exercise, on activity pattern, rate of perceived exertion (RPE), and blood lactate concentration. Twenty young, active men (mean age 26.2 +/- 2.1 years) performed a 6-minute run at peak oxygen consumption speed (predetermined from the VO(2) max test). The mean heart rate (HR), RPE, number of steps (determined by step counter), and blood lactate concentrations were determined at 3, 6, 9, 12, and 15 minutes during the recovery from the exercise, with and without motivational music (2 separate sessions, at random order). There was no difference in the mean HR during the recovery with and without music. Listening to motivational music during the recovery was associated with increased voluntary activity of the participants, determined by increased number of steps (499.4 +/- 220.1 vs. 413.2 +/- 150.6 steps, with and without music, respectively; p <= 0.05). The increased number of steps during the recovery was accompanied by a significantly greater decrease in blood lactate concentration percentage (28.1 +/ 12.2 vs. 22.8 +/- 10.9%, with and without music, respectively, p <= 0.05). This was associated with a greater decrease in RPE (77.7 +/- 14.4 vs. 73.1 +/- 14.7% with and without music, respectively; p <= 0.05). Our results suggest that listening to motivational music during nonstructured recovery from intense exercise leads to increased activity, faster lactate clearance, and reduced RPE and therefore may be used by athletes in their effort to enhance recovery. PMID- 22067238 TI - An exercise sequence for progression in balance training. AB - Compared with resistance training, information concerning the progressive configuration of balance training (BT) is rare and lacks scientific validation. Therefore, a study was designed to determine participants' ability to perform balance exercises with increasing level of difficulty. The task required the participants (N = 20) to stand as stable as possible on a computerized balance platform. The experiment was performed on 3 testing days using different stance and sensory conditions. On each day, bipedal, step, tandem, and monopedal stands were performed 3 times while sensory conditions changed from firm ground, eyes opened (day 1) over foam ground, eyes opened (day 2) to firm ground, eyes closed (day 3). The results showed that total center of pressure displacements significantly increased when the use of sensory information (comparison between testing days: all p < 0.001) or when the base of support (comparison within testing days: all p < 0.001) was gradually reduced. Based on the observed pattern of increased postural sway across all testing conditions and the levels of trial variability, exercises were categorized into several stages of training. Findings indicate that balance performance decreased in response to an increased level of task difficulty introduced by narrowing the base of support and by limiting the use of sensory information. Practitioners can use the derived exercise ranking to select exercises for BT appropriate to the level of participants' balance ability and to implement progression in balance training. PMID- 22067239 TI - Metabolic and cardiac autonomic effects of high-intensity resistance training protocol in Wistar rats. AB - The aim of this study was to assess the effects of metabolic and autonomic nervous control on high-intensity resistance training (HRT) as determined by pancreatic glucose sensitivity (GS), insulin sensitivity (IS), blood lactate ([La]), and heart rate variability (HRV) in rats. Thirty male, albino Wistar rats (292 +/- 20 g) were divided into 3 groups: sedentary control (SC), low-resistance training (LRT), and HRT. The animals in the HRT group were submitted to a high resistance protocol with a progressively increasing load relative to body weight until exhaustion, whereas the LRT group performed the same exercise regimen with no load progression. The program was conducted 3 times per week for 8 weeks. The [La], parameters related to the functionality of pancreatic tissue, and HRV were measured. There was a significant increase in peak [La] only in the HRT group, but there was a reduction in [La] when corrected to the maximal load in both trained groups (LRT and HRT, p < 0.05). Both trained groups exhibited an increase in IS; however, compared with SC and LRT, HRT demonstrated a significantly higher GS posttraining (p < 0.05). With respect to HRV, the low-frequency (LF) band, in milliseconds squared, reduced in both trained groups, but the high-frequency band, in milliseconds squared and nu, increased, and the LF in nu, decreased only in the HRT group (p < 0.05). The HRT protocol produced significant and beneficial metabolic and cardiac autonomic adaptations. These results provide evidence for the positive benefits of HRT in counteracting metabolic and cardiovascular dysfunction. PMID- 22067240 TI - Inflammatory response and neutrophil functions in players after a futsal match. AB - Inflammatory response and neutrophil functions in players after a futsal match. J Strength Cond Res 26(9): 2507-2514, 2012-Futsal players suffer injuries resulting from muscle fatigue and contact or collision among players. Muscle lesions can be detected by measuring muscle lesion markers such as creatine kinase (CK) and lactate dehydrogenase (LDH) in plasma. After an initial lesion, there is an increase in the plasma levels of C-reactive protein (CRP) and proinflammatory cytokines. These mediators may activate neutrophils and contribute to tissue damage and increase susceptibility to invasive microorganisms. In this study, we investigated the effect of a futsal match on muscle lesion markers, cytokines, and CRP in elite players. The basal and stimulated neutrophil responsiveness after a match was also evaluated based on measurements of neutrophil necrosis, apoptosis, phagocytic capacity, reactive oxygen species (ROS) production, and cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-8, IL-1beta, IL-10, and IL-1ra) production. Blood samples were taken from 16 players (26.4 +/- 3.2 years, 70.2 +/- 6.9 kg, 59.7 +/- 5.1 ml.kg.min, sports experience of 4.4 +/- 0.9 years) before and immediately after a match. Exercise increased the serum activities of CK (2.5-fold) and LDH (1.3-fold). Playing futsal also increased the serum concentrations of IL-6 (1.6-fold) and CRP (1.6-fold). The TNF-alpha, IL 1beta, IL-8, IL-1ra, and IL-10 serum levels were not modified in the conditions studied. The futsal match induced neutrophil apoptosis, as indicated by phosphatidylserine externalization (6.0-fold). The exercise induced priming of neutrophils by increasing ROS (1.3-fold), TNF-alpha (5.8-fold), and IL-1beta (4.8 fold) released in nonstimulated cells. However, in the stimulated condition, the exercise decreased neutrophil function, diminishing the release of ROS by phorbol myristate acetate-stimulated neutrophils (1.5-fold), and the phagocytic capacity (1.6-fold). We concluded that playing futsal induces inflammation, primes and activates neutrophils, and reduces the efficiency of neutrophil phagocytosis immediately after a match. PMID- 22067241 TI - Effect of different warm-up procedures on subsequent swim and overall sprint distance triathlon performance. AB - This study investigated the effect of 3 warm-up procedures on subsequent swimming and overall triathlon performance. Seven moderately trained, amateur triathletes completed 4 separate testing sessions comprising 1 swimming time trial (STT) and 3 sprint distance triathlons (SDT). Before each SDT, the athletes completed 1 of three 10-minute warm-up protocols including (a) a swim-only warm-up (SWU), (b) a run-swim warm-up (RSWU), and (c) a control trial of no warm-up (NWU). Each subsequent SDT included a 750-m swim, a 500-kJ (~20 km) ergometer cycle and a 5 km treadmill run, which the athletes performed at their perceived race intensity. Blood lactate, ratings of perceived exertion, core temperature, and heart rate were recorded over the course of each SDT, along with the measurement of swim speed, swim stroke rate, and swim stroke length. There were no significant differences in individual discipline split times or overall triathlon times between the NWU, SWU, and RSWU trials (p > 0.05). Furthermore, no difference existed between trials for any of the swimming variables measured (p > 0.05) nor did they significantly differ from the preliminary STT (p > 0.05). The findings of this study suggest that warming up before an SDT provides no additional benefit to subsequent swimming or overall triathlon performance. PMID- 22067242 TI - Evaluation of muscle activity during a standardized shoulder resistance training bout in novice individuals. AB - Momentary fatigue is an important variable in resistance training periodization programs. Although several studies have examined neuromuscular activity during single repetitions of resistance training, information is lacking in regard to neuromuscular fatigue indices throughout a full resistance training bout. The purpose of this study was to evaluate muscle activity during a shoulder resistance training bout with 15 repetitions maximum (RM) loadings in novice individuals. Twelve healthy sedentary women (age = 27-58 years; weight = 54-85 kg; height = 160-178 cm) were recruited for this study. Normalized electromyographic (nEMG) activity and median power frequency (MPF) of the upper, medial, and lower trapezius; the medial deltoid, infraspinatus, and serratus anterior was measured during 3 sets of 15RM during the exercises front raise, reverse flyes, shrugs, and lateral raise. For the majority of exercises, nEMG activity was high (>60% of maximal isometric contractions). From the first to the last repetition of each set nEMG-averaged for all muscles-increased 10. 0 +/- 0.4% (p < 0.05) and MPF decreased -7.7 +/- 0.5 Hz (p < 0.05). By contrast, nEMG activity and MPF were unchanged from the first to the third set (averaged for all muscles: 38.1 +/- 23.6 vs. 47.6 +/- 28.8% and 88.4 +/- 21.3 vs. 82.1 +/- 18.1 Hz, respectively). In conclusion, during a shoulder resistance training bout in novice individuals using 15RM loading muscle activity of the upper, medial, and lower trapezius, the medial deltoid, infraspinatus, and serratus anterior increased, and MPF decreased within each set-indicating momentary neuromuscular fatigue. By contrast, no such change was observed between the 3 sets. This indicates that momentary neuromuscular fatigue in shoulder resistance training is induced more efficiently within a set than between sets. PMID- 22067243 TI - Speed and agility of 12- and 14-year-old elite male basketball players. AB - The aims of this study were (a) to identify and compare the speed and agility of 12- and 14-year-old elite male basketball players and (b) to investigate relations between speed and agility for both age groups of basketball players, to help coaches to improve their work. Sixty-four players aged 12 (M = 11.98 years, SD = 0.311) and 54 players aged 14 (M = 14.092 years, SD = 0.275) were tested. Three agility tests: agility t-test, zigzag agility drill, and agility run 4 * 15 m and 3 speed tests: 20-m run, 30-m run, and 50-m run were applied. Fourteen-year old players achieved significantly better results in all speed and agility tests compared with 12-year-old players. The correlation coefficient (r = 0.81, p = 0.001) showed that 12-year-old players have the same ability in the 30- and 50-m runs. The other correlation coefficient (r = 0.59, p = 0.001) indicated that 20- and 30-m runs had inherently different qualities. The correlation coefficients between agility tests were <0.71, and therefore, each test in this group represents a specific task. In 14-year-old players, the correlation coefficients between the speed test results were <0.71. In contrast, the correlation coefficients between the agility tests were >0.71, which means that all the 3 tests represent the same quality. During the speed training of 12-year-old players, it is advisable to focus on shorter running distances, up to 30 m. During the agility training of the same players, it is useful to apply exercises with various complexities. In speed training of the 14-year-old players, the 30- and 50-m runs should be applied, and agility training should include more specific basketball movements and activities. PMID- 22067244 TI - Acute effects of a warm-up including active, passive, and dynamic stretching on vertical jump performance. AB - The purpose of this study was to examine the acute effects of 3 different stretching methods combined with a warm-up protocol on vertical jump performance. Sixteen young tennis players (14.5 +/- 2.8 years; 175 +/- 5.6 cm; 64.0 +/- 11.1 kg) were randomly assigned to 4 different experimental conditions on 4 successive days. Each session consisted of a general and specific warm-up, with 5 minutes of running followed by 10 jumps, accompanied by one of the subsequent conditions: (a) Control Condition (CC)-5 minutes of passive rest; (b) Passive Stretching Condition (PSC)-5 minutes of passive static stretching; (c) Active Stretching Condition (ASC)-5 minutes of active static stretching; and (d) Dynamic Stretching Condition (DC)-5 minutes of dynamic stretching. After each intervention, the subjects performed 3 squat jumps (SJs) and 3 countermovement jumps (CMJs), which were measured electronically. For the SJ, 1-way repeated measures analysis of variance (CC * PSC * ASC * DC) revealed significant decreases for ASC (28.7 +/- 4.7 cm; p = 0.01) and PSC (28.7 +/- 4.3 cm; p = 0.02) conditions when compared with CC (29.9 +/- 5.0 cm). For CMJs, there were no significant decreases (p > 0.05) when all stretching conditions were compared with the CC. Significant increases in SJ performance were observed when comparing the DC (29.6 +/- 4.9 cm; p = 0.02) with PSC (28.7 +/- 4.3 cm). Significant increases in CMJ performance were observed when comparing the conditions ASC (34.0 +/- 6.0 cm; p = 0.04) and DC (33.7 +/- 5.5 cm; p = 0.03) with PSC (32.6 +/- 5.5 cm). A dynamic stretching intervention appears to be more suitable for use as part of a warm-up in young athletes. PMID- 22067246 TI - A 6-month supervised employer-based minimal exercise program for police officers improves fitness. AB - The purpose of the study was to determine the effects of a 6-month supervised, job-specific moderate exercise program in police officers on body composition, cardiovascular and muscular fitness. Body weight (BW), body mass index (BMI), and cardiovascular and muscular fitness were assessed at baseline, after a 6-month supervised fitness program and at 12-month follow-up (18 months). One hundred sixty-five (n = 131 men and n = 34 women) young (mean +/- SEM, 26.4 +/- 1.9 years), overweight (BMI = 26.2 +/- 1.2 kg.m) police officers participated. Aerobic exercise progressed from 3 d.wk, 20 minutes per session at 60% of the heart rate reserve (HRR) to 5 d.wk, 30 minutes per session at 75% of HRR at 3 months, and this level was maintained until 6 months. Muscular strength training progressed using 8 different calisthenics exercises from 3 d.wk, 2 sets of 5 repetitions using the participant's own BW to 5 d.wk, 3 sets of 15 repetitions of the participant's own BW at 3 months, and this level was maintained until 6 months. Cardiovascular and muscular fitness was measured using a 0.25-mile obstacle course incorporating various job-specific exercises and expressed as the physical abilities test (PAT) time. There was a significant reduction in BMI ( 0.6 +/- 0.2 kg.m, p < 0.001) and BW (-2.8 +/- 2.3 kg) and reduction in PAT time ( 11.9 +/- 2.1%, p < 0.01) from baseline to 6 months. However, BMI (1.4 +/- 1.1 kg.m, p < 0.001), BW (5.1 +/- 3.0 kg, p < 0.01), and PAT time significantly increased (12.8 +/- 2.2%, p < 0.01) from 6 to 18 months. There were no sex by time differences. The practical applications of this study indicate that a supervised, job-specific exercise program for police officers improves fitness and body composition after 6 months in both men and women, but continued supervision of exercise program may be necessary for maintenance of health benefits. PMID- 22067247 TI - Electromyostimulation--a systematic review of the effects of different electromyostimulation methods on selected strength parameters in trained and elite athletes. AB - This is the first part of 2 studies that systematically review the current state of research and structure the results of selected electromyostimulation (EMS) studies in a way that makes accurate comparisons possible. This part will focus on the effects of EMS on strength enhancement. On the basis of these results, part 2 will deal with the influence of the training regimen and stimulation parameters on EMS training effectiveness to make recommendations for training control. Out of about 200 studies, 89 trials were selected according to predefined criteria: subject age (<35 years), subject health (unimpaired), EMS type (percutaneous stimulation), and study duration (>7 days). To evaluate these trials, we first defined appropriate categories according to the type of EMS (local or whole body) and type of muscle contraction (isometric, dynamic, isokinetic). Then, we established the most relevant strength parameters for high performance sports: maximal strength, speed strength, power, jumping and sprinting ability. Unlike former reviews, this study differentiates between 3 categories of subjects based on their level of fitness (untrained subjects, trained subjects, and elite athletes) and on the types of EMS methods used (local, whole-body, combination). Special focus was on trained and elite athletes. Untrained athletes were investigated for comparison purposes. This scientific analysis revealed that EMS is effective for developing physical performance. After a stimulation period of 3-6 weeks, significant gains (p < 0.05) were shown in maximal strength (isometric Fmax +58.8%; dynamic Fmax +79.5%), speed strength (eccentric isokinetic Mmax +37.1%; concentric isokinetic Mmax + 41.3%; rate of force development + 74%; force impulse + 29%; vmax + 19%), and power (+67%). Developing these parameters increases vertical jump height by up to +25% (squat jump +21.4%, countermovement jump +19.2%, drop jump +12%) and improves sprint times by as much as -4.8% in trained and elite athletes. With regard to the level of fitness, the analysis shows that trained and elite athletes, despite their already high level of fitness, are able to significantly enhance their level of strength to same extent as is possible with untrained subjects. The EMS offers a promising alternative to traditional strength training for enhancing the strength parameters and motor abilities described above. Because of the clear-cut advantages in time management, especially when whole body EMS is used, we can expect this method to see the increasing use in high performance sports. PMID- 22067248 TI - Repeated-sprint and change-of-direction abilities in physically active individuals and soccer players: training and testing implications. AB - The relationship between repeated-sprint ability (RSA) and repeated change-of direction (RCOD) matched on intervals and distances was investigated in this study. The discrimination abilities of the tests were also examined. Using a within-subject repeated measures design, 25 physically active individuals (ACTs), 16 college soccer players (COL), and 18 professional soccer players (PRO) performed the RSA and RCOD tests during which the fastest time (FT), average time (AT), total time (TT), and percentage decrement score (%Dec) were recorded. We concluded that RSA and RCOD tested separate motor abilities because the shared variance between them in the FT, AT, and TT was <=50%. Both RSA and RCOD tests were reliable (intraclass correlation coefficient ranged 0.79-0.90) and valid performance assessments in terms of construct in that they discriminated between ACT and soccer players (irrespective of the soccer skill level in this study). Specifically, the FT, AT, and TT (but not %Dec) of RSA and RCOD were significantly higher in ACT as compared with that in both COL and PRO (p < 0.05). Most values of the RSA/RCOD index in COL and PRO were 0.59, which were significantly higher than those of ACT (0.53, p < 0.05). We proposed the use of the RSA/RCOD index with a target value of 0.59 to prioritize and quantify the training needs of RSA and RCOD for soccer players. PMID- 22067249 TI - Metabolic syndrome is inversely related to cardiorespiratory fitness in male career firefighters. AB - Cardiovascular disease (CVD) accounts for 45% of on-duty fatalities among firefighters, occurring primarily in firefighters with excess CVD risk factors in patterns resembling the metabolic syndrome (MetSyn). Additionally, firefighters have a high prevalence of obesity and sedentary behavior suggesting that MetSyn is also common. Therefore, we assessed the prevalence of MetSyn in firefighters and its association with cardiorespiratory fitness (CRF) in a cross-sectional study of 957 male career firefighters. The CRF was measured by maximal exercise tolerance testing (standard metabolic equivalent [METS]). The MetSyn was defined according to modified criteria from the Joint Scientific Statement. Group differences were compared using chi-test and logistic regression. The prevalence of MetSyn was 28.3%. Firefighters in the lowest fitness category (METS <= 10) had a nearly 10-fold higher prevalence of MetSyn (51.2%) compared with colleagues in the highest fitness category (METS > 14) (MetSyn prevalence 5.2%) (p value < 0.0001, adjusted for age). In multivariate regression models, every 1-unit increase in METS decreased the odds of having the MetSyn by 31% (odds ratio 0.69 [95% confidence interval 0.63-0.76] [age adjusted]), whereas age had no significant effect after adjusting for CRF. We found a high prevalence of the MetSyn in this group of career emergency responders expected to be more active, fit, and relatively younger than the general population. Moreover, there is a highly significant inverse, dose-response association with CRF. Firefighters should be given strong incentives to improve their fitness, which would decrease prevalent MetSyn, a likely precursor of on-duty CVD events and contributor to CVD burden in this population. PMID- 22067250 TI - A simplified model to predict stress fracture in young elite combat recruits. AB - The purpose of the study was to develop a simple prediction model for stress fractures (SFs) in young male recruits to identify risk factors for SF. Data were collected from 57 young (18.5 +/- 0.5 years) male athletes before elite combat basic training (BT). Measurements included anthropometric variables, blood samples, fitness tests, bone quality (peripheral quantitative computed tomography [pQCT]), psychological assessment, nutritional habits, and history of physical activity. A medical evaluation was done periodically. The SFs were clinically diagnosed during the 1-year training and thereafter confirmed by bone scintigraphy. Three "simple to monitor" variables were found to be significantly (p < 0.05) related to SF occurrence during basic and advanced training: aerobic training frequency, aerobic training duration, and waist circumference. From these 3 variables, a new model was constructed that successfully predicted 85% of the soldiers with (n = 23) and without (n = 34) SF as follows:(Equation is included in full-text article.)where PSF is the stress fracture prediction according to the Log Odds (SF), Odds(SF) is the ratio between the probability of SF existence and nonexistence, ATn is the aerobic training (times per week), ATt is the aerobic training duration (minutes per week), and waist is the circumference (centimeters). This model was validated on a different database taken from another 59 elite combat recruits before BT and successfully predicted 76.5% of the soldiers with SF (n = 22) and without SF (n = 37). A young male recruit for elite combat unit is at a greater risk of developing SF if, before entering BT, he trained aerobically <2 times per week with each training >40 minutes and has a waist circumference of <75 cm. However, further evaluation is required for different combat recruits, ages, and training programs to validate these results. PMID- 22067251 TI - Physiological responses and perceived exertion during cycling with superimposed electromyostimulation. AB - The goal of the study was to evaluate and to quantify the effects of local electromyostimulation (EMS) during cycling on the cardiorespiratory system, muscle metabolism, and perceived exertion compared with cycling with no EMS. Ten healthy men (age: 24.6 +/- 3.2 years, V[Combining Dot Above]O2max: 54.1 +/- 6.0 ml.min.kg) performed 3 incremental cycle ergometer step tests, 1 without and 2 with EMS (30 and 85 Hz) until volitional exhaustion. Lactate values and respiratory exchange ratio were significantly higher at intensities >=75% peak power output (PPO) when EMS was applied. Bicarbonate concentration, base excess (BE), and Pco2 were significantly lower when EMS was applied compared with the control at intensities >=75% PPO. Saliva cortisol levels increased because of the exercise but were unaffected by EMS. Furthermore, EMS showed greater effects on CK levels 24 hours postexercise than normal cycling did. Rating of perceived exertion was significantly higher at 100% PPO with EMS. No statistical differences were found for heart rate, pH, and Po2 between the tested cycling modes. The main findings of this study are greater metabolic changes (lactate, respiratory exchange ratio, BE, (Equation is included in full-text article.), Pco2) during cycling with EMS compared with normal cycling independent of frequency, mainly visible at higher work rates. Because metabolic alterations are important for the induction of cellular signaling cascades and adaptations, these results lead to the hypothesis that applied EMS stimulations during cycling exercise might be an enhancing stimulus for skeletal muscle metabolism and related adaptations. Thus, superimposed EMS application during cycling could be beneficial to aerobic performance enhancements in athletes and in patients who cannot perform high workloads. However, the higher demand on skeletal muscles involved must be considered. PMID- 22067252 TI - Increasing the distance of an external focus of attention enhances standing long jump performance. AB - Numerous studies have demonstrated that using verbal instructions to direct a performers attention externally (i.e., toward the effect of the movement) significantly enhances motor skill performance. Limited research has also demonstrated that increasing the distance of an external focus relative to the body magnifies the effect of an external focus of attention. The purpose of this study was to investigate the effect of increasing the distance of an external focus of attention on standing long jump performance. Using a counterbalanced within-participant design, recreationally trained male subjects (n = 35) performed 2 standing long jumps following 3 different sets of verbal instructions (total of 6 jumps; each separated by 1 minute of seated rest). One set of instructions was designed to focus attention externally near the body (EXN); another set of instructions directed attention externally to a target farther from the body (EXF); the last set of instructions served as a control condition (CON) and did not encourage a specific focus of attention. The results indicated that the EXN and EXF conditions elicited jump distances that were significantly greater than the CON condition. In addition, the subjects in the EXF condition jumped significantly farther than those in the EXN condition. These findings suggest that increasing the distance of an external focus of attention, relative to the body, immediately improves standing long jump performance. PMID- 22067253 TI - Changes in Acid-base balance during simulated soccer match play. AB - This study evaluated changes in markers of acid-base balance that occurred during simulated soccer match play. Sixteen academy soccer players participated in a soccer match simulation that consisted of 90 minutes of soccer-specific exercise with skills throughout. Blood samples were obtained before exercise (preexercise), every 15 minutes during the simulation (15, 30, 45, 60, 75, and 90 minutes), and 10 minutes into the half-time break (half time). Blood lactate concentrations were elevated throughout exercise (preexercise: 1.5 +/- 0.12 mmol.L; 90 minutes: 6.1 +/- 0.7 mmol.L, time effect: p < 0.01, partial-eta = 0.740). Relative to preexercise values, actual blood bicarbonate (preexercise: 28.02 +/- 0.92 mmol.L; 90 minutes: 21.73 +/- 0.65 mmol.L, time effect = p < 0.01, partial-eta = 0.680), standard blood bicarbonate (preexercise: 25.97 +/- 0.43 mmol.L; 90 minutes: 22.87 +/- 0.31 mmol.L, time effect = p < 0.01, partial-eta = 0.667), base excess (preexercise: 2.40 +/- 0.54 mmol.L, 90 minutes: -1.57 +/- 0.39 mmol.L, time effect = p < 0.01, partial-eta = 0.664), and pH (preexercise: 7.44 +/- 0.01 units; 90 minutes: 7.39 +/- 0.01 units, time effect = p < 0.01, partial-eta = 0.542) were depressed throughout the exercise. Interestingly, blood bicarbonate, base excess, and pH recovered at half time (p > 0.05). This is the first study to provide data concerning the acid-base balance of familiarized soccer players during exercise that simulates soccer match play. These findings suggest that (a) blood pH is reduced during soccer-specific exercise and (b) although buffering capacity is reduced throughout exercise, it returns to normal during half time. Further research is warranted to develop interventions that can maintain acid-base balance throughout the full duration of a soccer match. PMID- 22067254 TI - Effects of MagProTM on muscle performance. AB - Athletes are on an endless quest to enhance performance and are frequently barraged by products that purport to contribute to various components of athletic activity. The purpose of this study was to determine if MagProTM influenced muscle flexibility or muscle endurance. This was a double-blind, randomized, controlled study using a repeated-measures design. The Institutional Review Board approved consent was obtained. The participants were healthy, physically active adults (n = 38 for phase 1; n = 18 for phase 2). Two creams were used: MagProTM (Mg cream) and a placebo. In phase 1, each cream was applied to the gastroc soleus muscles. A stretching protocol was completed, and ankle dorsiflexion was compared. In phase 2, 1 cream was applied to both quadriceps muscles. An endurance protocol using a Life Fitness bicycle was completed. The procedure was repeated with the other cream on the quadriceps muscle 1 week later. For the flexibility phase, an analysis of variance with repeated measures revealed no difference between the 2 creams (p = 0.50), but there was a change in the flexibility over time (p = 0.00). For the endurance phase, paired t-tests revealed that there was no significant difference between the first (p = 0.26) or second (p = 0.35) cycling bouts of either cream. Likewise, there were no differences between the first and second cycling bouts of both the creams (MagProTM p = 0.46; Placebo p = 0.08). Despite previous studies demonstrating improved performance with Mg supplements, MagProTM did not enhance the outcome measures of this study. Examination of alternative application techniques and other outcome measures would be appropriate. PMID- 22067255 TI - The effects of whole-body vibration in isolation or combined with strength training in female athletes. AB - The aims of this study were to assess the behavior of a vibrating platform under different conditions and to compare the effects of an 8-week periodized training program with whole-body vibration (WBV) alone or in combination with conventional strength training (ST). Vibrating frequencies, displacements, and peak accelerations were tested through a piezoelectric accelerometer under different conditions of load and subjects' position. Eighteen national-level female athletes were assigned to 1 of 3 different groups performing WBV, conventional ST, or a combination of the 2 (WBV + ST). Isometric maximal voluntary contraction, dynamic maximal concentric force, and vertical jump tests were performed before and after the conditioning program. Vibrating displacements and maximum accelerations measured on the device were not always consistent with their expected values calculated from the display and manufacturers' information (sinusoidal waveforms). The WBV alone or in combination with low-intensity resistance exercise did not seem to induce significant enhancements in force and power when compared with ST. It appears that WBV cannot substitute parts of ST loading in a cohort of young female athletes. However, vibration effects might be limited by the behavior of the commercial platforms as the one used in the study. More studies are needed to analyze the performances of devices and the effectiveness of protocols. PMID- 22067256 TI - Comparative analysis of miRNAs and their targets across four plant species. AB - BACKGROUND: MicroRNA (miRNA) mediated regulation of gene expression has been recognized as a major posttranscriptional regulatory mechanism also in plants. We performed a comparative analysis of miRNAs and their respective gene targets across four plant species: Arabidopsis thaliana (Ath), Medicago truncatula(Mtr), Brassica napus (Bna), and Chlamydomonas reinhardtii (Cre). RESULTS: miRNAs were obtained from mirBase with 218 miRNAs for Ath, 375 for Mtr, 46 for Bna, and 73 for Cre, annotated for each species respectively. miRNA targets were obtained from available database annotations, bioinformatic predictions using RNAhybrid as well as predicted from an analysis of mRNA degradation products (degradome sequencing) aimed at identifying miRNA cleavage products. On average, and considering both experimental and bioinformatic predictions together, every miRNA was associated with about 46 unique gene transcripts with considerably variation across species. We observed a positive and linear correlation between the number miRNAs and the total number of transcripts across different plant species suggesting that the repertoire of miRNAs correlates with the size of the transcriptome of an organism. Conserved miRNA-target pairs were found to be associated with developmental processes and transcriptional regulation, while species-specific (in particular, Ath) pairs are involved in signal transduction and response to stress processes. Conserved miRNAs have more targets and higher expression values than non-conserved miRNAs. We found evidence for a conservation of not only the sequence of miRNAs, but their expression levels as well. CONCLUSIONS: Our results support the notion of a high birth and death rate of miRNAs and that miRNAs serve many species specific functions, while conserved miRNA are related mainly to developmental processes and transcriptional regulation with conservation operating at both the sequence and expression level. PMID- 22067257 TI - Epigenetic-aging-signature to determine age in different tissues. AB - All tissues of the organism are affected by aging. This process is associated with epigenetic modifications such as methylation changes at specific cytosine residues in the DNA (CpG sites). Here, we have identified an Epigenetic-Aging Signature which is applicable for many tissues to predict donor age. DNA methylation profiles of various cell types were retrieved from public data depositories - all using the HumanMethylation27 BeadChip platform which represents 27,578 CpG sites. Five datasets from dermis, epidermis, cervical smear, T-cells and monocytes were used for Pavlidis Template Matching to identify 19 CpG sites that are continuously hypermethylated upon aging (R>0.6; p-value<10 13). Four of these CpG sites (associated with the genes NPTX2, TRIM58, GRIA2 and KCNQ1DN) and an additional hypomethylated CpG site (BIRC4BP) were implemented in a model to predict donor age. This Epigenetic-Aging-Signature was tested on a validation group of eight independent datasets corresponding to several cell types from different tissues. Overall, the five CpG sites revealed age-associated DNA-methylation changes in all tissues. The average absolute difference between predicted and real chronological age was about 11 years. This method can be used to predict donor age in various cell preparations - for example in forensic analysis. PMID- 22067258 TI - Body mass index at 11-13 weeks' gestation and pregnancy complications. AB - OBJECTIVE: To examine the association between body mass index (BMI) at 11-13 weeks' gestation and a wide range of adverse pregnancy outcomes after adjustment for confounding factors in obstetric history and maternal characteristics. METHODS: This was a prospective screening study for adverse obstetric outcomes in women with singleton pregnancies attending for their first routine hospital visit at 11(+0)-13(+6) weeks of gestation. The maternal weight and height were measured and the BMI was calculated. Regression analysis was performed to examine the association between BMI and each of the adverse pregnancy outcomes. RESULTS: We examined 41,577 pregnancies with a live fetus at 11-13 weeks. There was a significant contribution from maternal BMI, in addition to maternal characteristics and obstetric history, in the prediction of subsequent miscarriage, stillbirth, preeclampsia, gestational hypertension, gestational diabetes mellitus, delivery of small and large for gestational age neonates, and both elective and emergency cesarean section, but not spontaneous preterm delivery. The risk for each pregnancy complication increased exponentially with BMI, except for delivery of small for gestational age neonates which decreased with BMI. CONCLUSIONS: Maternal BMI at 11-13 weeks can be combined with other maternal characteristics and obstetric history to estimate patient-specific risks for many pregnancy complications. PMID- 22067259 TI - Characterization of a novel oral glucocorticoid system and its possible role in disease. AB - Synthetic corticosteroids are used widely for the treatment of a variety of diseases of the mouth. However, little is known as to whether the oral mucosa is able to modulate the local concentration of active corticosteroids or to produce steroids de novo. This has important clinical implications, because tissue specific regulation of glucocorticoids is a key determinant of the clinical efficacy of these drugs. In the present study, we show that oral fibroblasts and keratinocytes expressed ACTH receptor (MC2R), glucocorticoid receptor (GR), and 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). Unlike keratinocytes, fibroblasts lacked 11beta-HSD2 and could not effectively deactivate exogenously administered cortisol. However, both cell types were able not only to activate cortisone into the active form cortisol, but also to synthesize cortisol de novo following stimulation with ACTH. 11beta-HSD2, the enzyme controlling cortisol deactivation, exhibited different patterns of expression in normal (squamous epithelium and salivary glands) and diseased oral mucosa (squamous cell carcinoma and mucoepidermoid carcinoma). Blocking of endogenous cortisol catabolism in keratinocytes with the 11beta-HSD2 inhibitor 18beta-glycyrrhetinic acid mimicked the effect of exogenous administration of hydrocortisone and partially prevented the detrimental effects induced by pemphigus vulgaris sera. Analysis of the data demonstrates that a novel, non-adrenal glucocorticoid system is present in the oral mucosa that may play an important role in disease. PMID- 22067260 TI - Chronic administration of tibolone modulates anxiety-like behavior and enhances cognitive performance in ovariectomized rats. AB - Hormone replacement therapy (HRT) may be prescribed to prevent the symptoms of menopause. This therapy may include estrogenic and/or progestin components and may increase the incidence of endometrial and breast cancers. Tibolone (TIB), which is also made up of estrogen and progestin components, is often used to reduce the impact of HRT. However, the effect of TIB on the processes of learning, memory and anxiety has yet to be fully elucidated. The aim of this study was to evaluate the long-term effect on learning, memory processes and anxiety in ovariectomized rats caused by different doses of TIB (0 mg/kg, 0.01 mg/kg, 0.1 mg/kg 1.0 mg/kg and 10 mg/kg, administered daily via the oral route for 18 weeks). Two behavioral animal models, the autoshaping and T maze models were employed. The concentrations of acetyl choline transferase (ChAT) and tryptophan hydroxylase (TPH) in the hippocampus were directly measured by Western blot. No significant changes were observed in the autoshaping model and spontaneous activity test. In the T maze, increased latency was observed with TIB doses of 1 and 10 mg/kg compared to the vehicle. We observed that the ChAT content decreased with increasing doses of TIB, whereas TPH content increased with doses of 1 and 10 mg/kg of TIB. These data indicate that high doses of TIB improved emotional learning, which may be related to the modulation of the cholinergic and serotonergic systems by TIB. PMID- 22067261 TI - Photoperiodicity and increasing salinity as environmental cues for reproduction in desert adapted rodents. AB - Understanding the ways environmental signals, regulate reproduction and reproductive behavior of desert adapted rodents is a major gap in our knowledge. In this study, we assessed the roles of photoperiod and diet salinity, as signals for reproduction. We challenged desert adapted common spiny mice, Acomys cahirinus, males and females with osmotic stress, by gradually increasing salinity in their water source - from 0.9% to 5% NaCl under short and long days (SD and LD, respectively). Photoperiodicity affected testosterone levels, as under LD-acclimation, levels were significantly (p<0.05) higher than under SD acclimation. Salinity treatment (ST) significantly reduced SD-acclimated male body mass (W(b)) and testis mass (p<0.005; normalized to W(b)). ST-LD-females significantly (p<0.005) decreased progesterone levels and the numbers of estrous cycles. A reduction in white adipose tissue (WAT) to an undetectable level was noted in ST-mice of both sexes under both photoperiod regimes. Receptors for vasopressin (VP) and aldosterone were revealed on testes of all male groups and on WAT in control groups. Our results suggest that photoperiod serves as an initial signal while water availability, expressed by increased salinity in the water source, is an ultimate cue for regulation of reproduction, in both sexes of desert-adapted A. cahirinus. We assume that environmental changes also affect behavior, as water seeking behavior by selecting food items, or locomotor activity may change in extreme environment, and thus indirectly affect reproduction and reproductive behavior. The existence of VP and aldosterone receptors in the gonads and WAT suggests the involvement of osmoregulatory hormones in reproductive control of desert adapted rodents. PMID- 22067262 TI - Evaluation of the humoral immune response in adult dairy cattle three years after vaccination with a bluetongue serotype 8 inactivated vaccine. AB - Despite the widespread use of bluetongue serotype 8 (BTV-8) inactivated vaccines across Europe from 2008 to 2011, two very practical questions remain unanswered about the length of persistence of group-specific antibodies in milk and serum post-vaccination and the duration of protection beyond one year post-vaccination. This study has firstly revealed that group-specific antibodies persist at high levels in milk and serum in the majority of cattle for at least 3 years post vaccination, thus removing the option of using these animals in ELISA-based surveillance programmes. Secondly neutralising antibodies have been shown to persist in the majority of cattle for at least 3 years post-vaccination, indicating that the cattle are likely to be protected for this time period. This extended duration of protection may have contributed towards the rapid and efficient eradication of BTV-8 from many European countries, despite reducing levels of vaccine coverage. PMID- 22067263 TI - Vaccination with NS1-truncated H3N2 swine influenza virus primes T cells and confers cross-protection against an H1N1 heterosubtypic challenge in pigs. AB - The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1Delta126 TX98) is attenuated and immunogenic when delivered intranasally in young pigs. We analyzed T-cell priming and cross-protective efficacy in weanling piglets after intranasal inoculation with NS1Delta126 TX98 versus wild type TX98. In vivo replication of the truncation mutant was minimal compared to the wild type virus. T-cell responses were greater in magnitude in pigs infected with the wild type virus in in vitro restimulation assays. According to the expression of activation marker CD25, peripheral T cell recall responses in NS1Delta126 TX98 infected pigs were minimal. However, intracellular IFN-gamma data indicate that the attenuated virus induced virus-specific CD4(+)CD8(-), CD4(+)CD8(+), CD4(-)CD8(+), and gammadelta T cells within 28 days. The IFN-gamma response appeared to contract, as responses were reduced at later time points prior to challenge. CD4(+)CD8(+) cells isolated 5 days after heterosubtypic H1N1 challenge (day 70 overall) showed an elevated CD25 response to virus restimulation. Pigs previously infected with wild type TX98 were protected from replication of the H1N1 challenge virus. Vaccination with NS1Delta126 TX98 was associated with significantly lower levels of Th1 associated cytokines in infected lungs but provided partial cross-protection against the H1N1 challenge. These results demonstrate that NS1Delta SIV vaccines can elicit cell-mediated cross-protection against antigenically divergent strains. PMID- 22067264 TI - Lung function reduction and chronic respiratory symptoms among workers in the cement industry: a follow up study. AB - BACKGROUND: There are only a few follow-up studies of respiratory function among cement workers. The main aims of this study were to measure total dust exposure, to examine chronic respiratory symptoms and changes in lung function among cement factory workers and controls that were followed for one year. METHODS: The study was conducted in two cement factories in Ethiopia. Totally, 262 personal measurements of total dust among 105 randomly selected workers were performed. Samples of total dust were collected on 37-mm cellulose acetate filters placed in closed faced Millipore-cassettes. Totally 127 workers; 56 cleaners, 44 cement production workers and 27 controls were randomly selected from two factories and examined for lung function and interviewed for chronic respiratory symptoms in 2009. Of these, 91 workers; 38 cement cleaners (mean age 32 years), 33 cement production workers (36 years) and 20 controls (38 years) were examined with the same measurements in 2010. RESULTS: Total geometric mean dust exposure among cleaners was 432 mg/m(3). The fraction of samples exceeding the Threshold Limit Value (TLV) of 10 mg/m(3) for the cleaners varied from 84-97% in the four departments. The levels were considerably lower among the production workers (GM = 8.2 mg/m(3)), but still 48% exceeded 10 mg/m(3).The prevalence of all the chronic respiratory symptoms among both cleaners and production workers was significantly higher than among the controls.Forced Expiratory Volume in one second (FEV(1)) and FEV(1)/Forced Vital Capacity (FEV(1)/FVC) were significantly reduced from 2009 to 2010 among the cleaners (p < 0.002 and p < 0.004, respectively) and production workers (p < 0.05 and p < 0.02, respectively), but not among the controls. CONCLUSIONS: The high prevalence of chronic respiratory symptoms and reduction in lung function is probably associated with high cement dust exposure. Preventive measures are needed to reduce the dust exposure. PMID- 22067265 TI - The feasibility of endocardial propagation mapping using magnetic resonance guidance in a Swine model, and comparison with standard electroanatomic mapping. AB - The introduction of electroanatomic mapping (EAM) has improved the understanding of the substrate of ventricular tachycardia. EAM systems are used to delineate scar regions responsible for the arrhythmia by creating voltage or activation time maps. Previous studies have identified the benefits of creating MR-guided voltage maps; however, in some cases voltage maps may not identify regions of slow propagation that can cause the reentrant tachycardia. In this study, we obtained local activation time maps and analyzed propagation properties by performing MR-guided mapping of the porcine left ventricle while pacing from the right ventricle. Anatomical and myocardial late gadolinium enhancement images were used for catheter navigation and identification of scar regions. Our MR guided mapping procedure showed qualitative correspondence to conventional clinical EAM systems in healthy pigs and demonstrated altered propagation in endocardial infarct models. PMID- 22067266 TI - A Bayesian framework for automated cardiovascular risk scoring on standard lumbar radiographs. AB - We present a fully automated framework for scoring a patient's risk of cardiovascular disease (CVD) and mortality from a standard lateral radiograph of the lumbar aorta. The framework segments abdominal aortic calcifications for computing a CVD risk score and performs a survival analysis to validate the score. Since the aorta is invisible on X-ray images, its position is reasoned from 1) the shape and location of the lumbar vertebrae and 2) the location, shape, and orientation of potential calcifications. The proposed framework follows the principle of Bayesian inference, which has several advantages in the complex task of segmenting aortic calcifications. Bayesian modeling allows us to compute CVD risk scores conditioned on the seen calcifications by formulating distributions, dependencies, and constraints on the unknown parameters. We evaluate the framework on two datasets consisting of 351 and 462 standard lumbar radiographs, respectively. Promising results indicate that the framework has potential applications in diagnosis, treatment planning, and the study of drug effects related to CVD. PMID- 22067267 TI - Dynamics of a contrast agent microbubble attached to an elastic wall. AB - A modified Rayleigh-Plesset equation is derived to model the oscillation of a contrast agent microbubble attached to an elastic wall. The obtained equation shows that contact with the wall affects the bubble oscillation as if the bubble oscillated in a liquid with a changed (effective) density. Depending on the wall properties, the effective density can be either higher or lower than the real liquid density and hence the natural frequency of the attached bubble can be either lower or higher than the natural frequency of the same bubble in an unbounded liquid. Numerical simulations are made for a contrast bubble with shell properties similar to those used in the Marmottant shell model. The cases of a rigid wall and a plastic wall are compared. The properties of the plastic wall are set to correspond to walls of OptiCell chambers commonly used in experiments. It is shown that contact with the rigid wall decreases the natural frequency of the bubble as compared to its natural frequency in an unbounded liquid, whereas contact with the OptiCell wall increases the natural frequency of the bubble. Bubble resonance curves for three cases are compared: the bubble in an unbounded liquid; the bubble at a distance from an OptiCell wall; the bubble in contact with an OptiCell wall. Results obtained for a 2- MUm -radius bubble insonified with a 10-cycle, 40 kPa, 2.1 MHz Gaussian pulse show that contact with the OptiCell wall leads to the following effects. The amplitude of the radial oscillation of the attached bubble is decreased by about 70% as compared to that of the same bubble in an unbounded liquid. The fundamental component in the spectrum of the scattered pressure of the attached bubble is decreased by 12 dB. A strong second harmonic appears in the spectrum of the scattered pressure of the attached bubble; its magnitude is about 11.5 dB higher than the level corresponding to the case of an unbounded liquid. PMID- 22067268 TI - Usefulness of repeated recombinant human thyrotropin-stimulated thyroglobulin test in the post-surgical follow-up of very low-risk patients with differentiated thyroid carcinoma. AB - BACKGROUND: The European Thyroid Association (ETA) and the American Thyroid Association (ATA) guidelines identify subgroups of patients affected by thyroid carcinoma in whom, due to a low risk of recurrence, radioiodine ablation is not indicated. These patients are referred to as "very low-risk" according to the ETA consensus and "low-risk" patients according to the ATA guidelines. The recommended post-surgical follow-up of these patients is based upon periodical measurements of serum thyroglobulin (Tg) on levothyroxine therapy and neck ultrasound (US). AIM: To evaluate the usefulness of recombinant human (rh)-TSH Tg test and its repetition 2-3 yr afterwards in very low-risk patients. MATERIALS AND METHODS: We consecutively enrolled 32 patients with undetectable anti-Tg antibodies. Basal serum Tg levels was undetectable in all patients. RESULTS: Following rhTSH serum Tg remained undetectable in 23 (71.9%) patients (UP) and was >1.0 ng/ml in 9 (DP). US and whole body scan, revealed lymph node metastasis in 4/9 DP patients. A second rhTSH stimulation test (36.9+/-3.5 months later) was performed in all UP and in 5 DP patients without proven recurrences. All the UP and 4/5 formerly DP patients showed undetectable Tg stimulation. CONCLUSIONS: Our results suggest that rhTSH Tg test may be helpful in very low-risk patients, given its ability to differentiate those who may be considered "free of disease" from those who require further investigation and treatment. Repeated rhTSH Tg tests may be indicated only in patients with detectable serum Tg at prior stimulation testing. PMID- 22067269 TI - Joint impact of donor and recipient parameters on the outcome of liver transplantation in Germany. AB - BACKGROUND: The shortage of donor organs in Germany has led to the use of organs from donors with extended donor criteria (EDC). EDC have been defined on the basis of expert opinions, but their clinical relevance is controversial. This may cause loss of organs otherwise available for transplantation. We evaluated the impact of donor and recipient factors in liver transplants on patient and graft survival in a nationwide multicenter analysis, with special focus on EDC and donor risk index. METHODS: A database was created from data on livers donated and transplanted in Germany between 2006 and 2008 as provided by Deutsche Stiftung Organ transplantation and BQS Institute. Cox regression (significance level 5%, risk ratio [95% confidence interval]) was used for calculating the impact on patient survival (n=2095) and on graft survival (n=2175). RESULTS: Patient and graft survival were significantly affected only by donor age (1.012 and 1.011/year), recipient age (1.019 and 1.014/year), creatinine (1.248 and 1.205/mg/dL), bilirubin (1.022 and 1.023/mg/dL), and high urgency status (1.783 and 1.809). Inferior organ quality resulted in lower graft survival (1.243) and donor history of smoking in lower patient survival (1.249). CONCLUSION: Multiple Cox regression revealed no significant impact of EDC or donor risk index on patient and graft survival except for donor age after donor selection at recovery. Among recipient variables, only age, creatinine and bilirubin, and high urgency status were associated with poorer outcome. PMID- 22067270 TI - Impact of early conversion from tacrolimus to sirolimus on chronic allograft changes in kidney recipients on rapid steroid withdrawal. AB - BACKGROUND: Calcineurin-inhibitor therapy is a contributing factor to the origin of interstitial fibrosis and tubular atrophy (IFTA). METHODS: We conducted a prospective randomized trial of conversion of tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal. We compared the chronic changes (IFTA and sum of Banff chronic scores--Total Score) on protocol biopsies at 1 month, 1 year, and 2 years in all randomized patients. We compared the outcomes between treatment groups and analyzed the impact of previous rejection on the chronic changes. RESULTS: We randomized 122 patients, 62 to sirolimus and 60 to tacrolimus. The 1-year biopsy was performed in 54 patients (90%) of the tacrolimus group and 56 patients (90%) of the sirolimus group. The proportion of biopsies with IFTA more than or equal to 2 and the Total Score more than 2 increased over the 2 years but were not different between the study groups at any time point. On the 1-year biopsy, there was more IFTA, and the fraction with Total Score more than 2 was higher in the tacrolimus group with previous rejection. In the cohort without rejection, there was a significant progression of the IFTA and Total Score between 1 and 2 years in both the sirolimus and tacrolimus groups. CONCLUSION: Conversion from tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal does not decrease the progression of chronic changes on protocol biopsies during the first 2 years even in those patients without previous acute rejection. PMID- 22067271 TI - QT dispersion and cardiac involvement in children with Familial Mediterranean fever. AB - Familial Mediterranean fever is a hereditary disease characterised by recurrent and self-terminated attacks of fever and polyserositis. An earlier study found that adult patients of Familial Mediterranean fever had an abnormally longer QT dispersion and corrected QT dispersion, markers for ventricular arrhythmogenicity. QT dispersion is a simple non-invasive arrhythmogenic marker that can be used to assess homogeneity of cardiac repolarisation; however, it has not been studied in children with Familial Mediterranean fever before. The aim of this study was to assess QT dispersion and corrected QT dispersion, and their relationship with systolic and diastolic function of the left ventricle in a group of children with Familial Mediterranean fever. We performed electrocardiography and Doppler echocardiography on patients and controls. Maximum QT, minimum QT, QT dispersion, corrected QT, maximum corrected QT, minimum corrected QT, and corrected QT dispersion intervals were measured from standard 12-lead electrocardiography. No statistically significant differences were found between the groups in QT dispersion, corrected QT dispersion, and systolic-diastolic function of the left ventricle parameters. During the 12 months of follow-up, no ventricular arrhythmias were documented in either group. PMID- 22067273 TI - An autoimmune disease prevented by anti-retroviral drugs. AB - BACKGROUND: Both Aicardi-Goutieres syndrome, a Mendelian mimic of congenital infection, and the autoimmune disease systemic lupus erythematosus can result from mutations in the gene encoding the enzyme Trex1. In mice, the absence of Trex1 causes severe myocarditis. The enzyme is thought to degrade endogenous retroelements, thus linking them to autoimmune disease. However, inhibition of reverse transcription by the inhibitor zidovudine (AZT) did not ameliorate the disease, weakening the link to retroelements. FINDINGS: Here, we show that two other FDA-approved drugs that inhibit reverse transcriptase can ameliorate the myocarditis in Trex1-null mouse. CONCLUSIONS: The result suggests that retroelements contribute to this hereditary form of autoimmunity, and that treatment with retroelement inhibitors might ameliorate Aicardi-Goutieres syndrome in humans. PMID- 22067275 TI - Adaptive timing of detachment in a tick parasitizing hole-nesting birds. AB - In non-permanent parasites with low intrinsic mobility such as ticks, dispersal is highly dependent on host movements as well as the timing of separation from the hosts. Optimal detachment behaviour is all the more crucial in nidicolous ticks as the risk of detaching in non-suitable habitat is high. In this study, we experimentally investigated the detachment behaviour of Ixodes arboricola, a nidicolous tick that primarily infests birds roosting in tree-holes. We infested great tits with I. arboricola larvae or nymphs, and submitted the birds to 2 experimental treatments, a control treatment in which birds had normal access to nest boxes and an experimental treatment, in which the birds were prevented access to their nest boxes for varying lengths of time. In the control group, most ticks detached within 5 days, whereas in the experimental group, ticks remained on the bird for as long as the bird was prevented access (up to 14 days). This prolonged attachment caused a decrease in survival and engorgement weight in nymphs, but not in larvae. The capacity of I. arboricola larvae to extend the duration of attachment in non-suitable environments with no apparent costs, may be an adaptation to unpredictable use of cavities by roosting hosts during winter, and at the same time may facilitate dispersal of the larval instars. PMID- 22067274 TI - Global analysis of gene expression in NGF-deprived sympathetic neurons identifies molecular pathways associated with cell death. AB - BACKGROUND: Developing sympathetic neurons depend on nerve growth factor (NGF) for survival and die by apoptosis after NGF withdrawal. This process requires de novo gene expression but only a small number of genes induced by NGF deprivation have been identified so far, either by a candidate gene approach or in mRNA differential display experiments. This is partly because it is difficult to obtain large numbers of sympathetic neurons for in vitro studies. Here, we describe for the first time, how advances in gene microarray technology have allowed us to investigate the expression of all known genes in sympathetic neurons cultured in the presence and absence of NGF. RESULTS: We have used Affymetrix Exon arrays to study the pattern of expression of all known genes in NGF-deprived sympathetic neurons. We identified 415 up- and 813 down-regulated genes, including most of the genes previously known to be regulated in this system. NGF withdrawal activates the mixed lineage kinase (MLK)-c-Jun N-terminal kinase (JNK)-c-Jun pathway which is required for NGF deprivation-induced death. By including a mixed lineage kinase (MLK) inhibitor, CEP-11004, in our experimental design we identified which of the genes induced after NGF withdrawal are potential targets of the MLK-JNK-c-Jun pathway. A detailed Gene Ontology and functional enrichment analysis also identified genetic pathways that are highly enriched and overrepresented amongst the genes expressed after NGF withdrawal. Five genes not previously studied in sympathetic neurons - trib3, ddit3, txnip, ndrg1 and mxi1 - were validated by real time-PCR. The proteins encoded by these genes also increased in level after NGF withdrawal and this increase was prevented by CEP-11004, suggesting that these genes are potential targets of the MLK-JNK-c-Jun pathway. CONCLUSIONS: The sympathetic neuron model is one of the best studied models of neuronal apoptosis. Overall, our microarray data gives a comprehensive overview of, and provides new information about, signalling pathways and transcription factors that are regulated by NGF withdrawal. PMID- 22067276 TI - Considerations on the measurement of follicular squamous cell carcinoma. PMID- 22067277 TI - Effects of administration of hormone therapy or raloxifene on the immune system and on biochemical markers of bone remodeling. AB - OBJECTIVE: Over the last few years, conclusive evidence of the involvement of the immune system in the regulation of bone metabolism has been identified. Consequently, one question that should be formulated concerns the possible effects of antiresorptive therapies on the immune system. Therefore, the purpose of the present work was to evaluate both the functionality of the immune system and bone turnover in women receiving antiresorptive therapies, such as hormone therapy (HT; n = 33) and raloxifene (RLX; n = 66), acting through estrogen receptors. METHODS: To that end, this study analyzed bone turnover markers in a population of postmenopausal women before and after beginning therapy and compared these with data of women not treated (NT; n = 102). In a subgroup of participants (NT = 33, RLX = 24, and HT = 26), we analyzed the effects of treatments on immune system parameters such as serum levels of interleukin (IL) 6, tumor necrosis factor alpha, and IL-1beta; lymphocyte subpopulations; cell proliferation by peripheral blood mononuclear cells (PBMCs); in vitro production of IL-1beta by PBMCs; and the expression of receptor activator of nuclear factor kappaB ligand, transforming growth factor beta, and IL-4 genes by PBMCs. RESULTS: The results showed that bone resorption was inhibited strongly in women in the RLX and HT groups when compared with women in the NT group. Interestingly, the administration of RLX inhibited the production of the Wnt/beta-catenin signaling pathway inhibitor Dickkopf Homolog-1 (P < 0.05) and tended to increase the levels of the osteoclastogenesis inhibitor osteoprotegerin at month 6 (P = 0.059). With regard to the immune system, the different treatments did not markedly perturb the parameters analyzed, with the exception of the increase in serum IL-1beta detected in the HT group at month 6 (P < 0.05). CONCLUSIONS: The main conclusions of the present work were that HT or RLX do not disturb the immune system and that both treatments have a similar antiresorptive power. PMID- 22067278 TI - Optimal waist circumference cutoff value for defining the metabolic syndrome in postmenopausal Latin American women. AB - OBJECTIVE: The aim of this study was to determine an optimal waist circumference (WC) cutoff value for defining the metabolic syndrome (METS) in postmenopausal Latin American women. METHODS: A total of 3,965 postmenopausal women (age, 45-64 y), with self-reported good health, attending routine consultation at 12 gynecological centers in major Latin American cities were included in this cross sectional study. Modified guidelines of the US National Cholesterol Education Program, Adult Treatment Panel III were used to assess METS risk factors. Receiver operator characteristic curve analysis was used to obtain an optimal WC cutoff value best predicting at least two other METS components. Optimal cutoff values were calculated by plotting the true-positive rate (sensitivity) against the false-positive rate (1 - specificity). In addition, total accuracy, distance to receiver operator characteristic curve, and the Youden Index were calculated. RESULTS: Of the participants, 51.6% (n = 2,047) were identified as having two or more nonadipose METS risk components (excluding a positive WC component). These women were older, had more years since menopause onset, used hormone therapy less frequently, and had higher body mass indices than women with fewer metabolic risk factors. The optimal WC cutoff value best predicting at least two other METS components was determined to be 88 cm, equal to that defined by the Adult Treatment Panel III. CONCLUSIONS: A WC cutoff value of 88 cm is optimal for defining METS in this postmenopausal Latin American series. PMID- 22067279 TI - The effect of red blood cell transfusion on tissue oxygenation and microcirculation in severe septic patients. AB - BACKGROUND: Microcirculation plays a vital role in the development of multiple organ failure in severe sepsis. The effects of red blood cell (RBC) transfusions on these tissue oxygenation and microcirculation variables in early severe sepsis are not well defined. METHODS: This is a prospective, observational study of patients with severe sepsis requiring RBC transfusions of one to two units of non leukoreduced RBCs for a hemoglobin < 7.0, or for a hemoglobin between 7.0 and 9.0 with lactic acidosis or central venous oxygen saturation < 70%. This study took place in a 54-bed, medical-surgical intensive care unit of a university affiliated hospital. Thenar tissue oxygen saturation was measured by using a tissue spectrometer on 21 patients, and a vaso-occlusive test was performed before and 1 hour after transfusion. The sublingual microcirculation was assessed with a Sidestream Dark Field device concomitantly on 11 of them. RESULTS: RBC transfusion resulted in increase in hemoglobin (7.23 (+/- 0.87) to 8.75 (+/- 1.06) g/dl; p < 0.001). RBC transfusion did not globally affect near-infrared spectrometry (NIRS)-derived variables. However, percent change in muscle oxygen consumption was negatively correlated with baseline (r = - 0.679, p = 0.001). There was no statistically significant correlation between percent change in vascular reactivity and baseline (p = 0.275). There was a positive correlation between percent change in oxygen consumption and percent change in vascular reactivity (r = 0.442, p = 0.045). In the 11 patients, RBC transfusion did not globally affect NIRS-derived variables or SDF-derived variables. There was no statistically significant correlation between percent change in small vessel perfusion and baseline perfusion (r = -0.474, p = 0.141), between percent change in small vessel flow and baseline flow (r = -0.418, p = 0.201), or between percent change in small vessel perfusion and percent change in small vessel flow (r = 0.435, p = 0.182). CONCLUSIONS: In a small sample population, muscle tissue oxygen consumption, microvascular reactivity and sublingual microcirculation were globally unaltered by RBC transfusion in severe septic patients. However, muscle oxygen consumption improved in patients with low baseline and deteriorated in patients with preserved baseline. Future research with larger samples is needed to further examine the association between RBC transfusion and outcomes of patients resuscitated early in severe sepsis, with an emphasis on elucidating the potential contribution of microvascular factors. PMID- 22067280 TI - External exercise information provides no immediate additional performance benefit to untrained individuals in time trial cycling. AB - OBJECTIVE: To determine the importance of the provision of external exercise information to the setting of the pacing strategy, in subjects unfamiliar with a cycling task. DESIGN: Twenty-two healthy, untrained cyclists (VO(2max), 50 +/- 9 mL-(1).kg-(1).min-(1)) were randomly assigned to a control (CON) group or an experimental (EXP) group and two successive 4 km time trials (TT) were performed, separated by a 17 min recovery. The CON group received distance knowledge and distance feedback; the EXP group received neither, but knew that each TT was to be of the same distance. RESULTS: No significant difference in completion time (p>0.05) was observed between the groups for either time to complete TT one (TT1) (CON=443 +/- 33 s versus EXP=471 +/- 63 s) or time to complete TT two (time trial 2) (CON=461 +/- 37 s versus EXP=501 +/- 94 s). No significant difference in the final RPE was observed between groups. However, a significant interaction for RPE (rating of perceived exertion)*TT in the CON was observed (F7,70=5.32, p<0.05), with significantly higher RPE values in the final kilometre of TT2 (p<0.05). CONCLUSION: The lack of any performance improvement in either group, despite the differences in exercise information received, indicates both a reliance on the afferent feedback for setting a pacing strategy and slow learning effect from practice in subjects unfamiliar with the task. The modification in RPE profile observed in the CON, despite no performance improvement, suggests exercise perception based changes may pre-empt work rate based changes and thus not immediately translate to improved performance. PMID- 22067281 TI - More research is needed into the effects on injury of substitute and interchange rules in team sports. PMID- 22067282 TI - European consensus on epidemiological studies of injuries in the thoroughbred horse racing industry. PMID- 22067283 TI - Events leading to anterior cruciate ligament injury in World Cup Alpine Skiing: a systematic video analysis of 20 cases. AB - BACKGROUND: The authors have recently identified three main mechanisms for anterior cruciate ligament (ACL) injuries among World Cup (WC) alpine skiers, termed as "the slip-catch", "the landing back-weighted" and "the dynamic snowplow". However, for a more complete understanding of how these injuries occur, a description of the events leading to the injury situations is also needed. OBJECTIVE: To describe the skiing situation leading to ACL injuries in WC alpine skiing. METHODS: Twenty cases of ACL injuries reported through the International Ski Federation Injury Surveillance System (FIS ISS)for three consecutive WC seasons (2006-2009) were obtained on video. Ten experts (9 WC coaches, 1 former WC athlete) performed visual analyses of each case to describe in their own words, factors they thought may have contributed to the injury situation related to different predefined categories: (1) skier technique, (2) skier strategy, (3) equipment, (4) speed and course setting, (5) visibility, snow and piste conditions and (6) any other factors. RESULTS: Factors related to the three categories, namely skier technique, skier strategy, and visibility, snow and piste conditions, were assumed to be the main contributors to the injury situations. Skier errors, technical mistakes and inappropriate tactical choices, were the dominant factors. In addition, bumpy conditions, aggressive snow, reduced visibility and course difficulties were assumed to contribute. CONCLUSION: Based on this systematic video analysis of 20 injury situations, factors related to skier technique, skier strategy and specific race conditions were identified as the main contributors leading to injury situations. PMID- 22067285 TI - Telemedical home-monitoring of diabetic foot disease using photographic foot imaging--a feasibility study. AB - We assessed the feasibility of using a photographic foot imaging device (PFID) as a tele-monitoring tool in the home environment of patients with diabetes who were at high risk of ulceration. Images of the plantar foot were taken three times a week over a period of four months in the home of 22 high-risk patients. The images were remotely assessed by a diabetic foot specialist. At the end of the study, 12% of images were missing, mainly due to modem or server failures (66%), or non-adherence (11%). All three referrals for diagnosed ulcers and 31 of 32 referrals for abundant callus resulted in treatment. Health-related quality of life (EQ-5D visual analogue scale), increased from 7.5 at baseline to 7.9 at end of follow-up, but not significantly. Mean scores on a visual analogue scale for different usability domains (independence, ease of use, technical aspects and value) ranged from seven to nine. The study demonstrates the feasibility of using the PFID for the early diagnosis of foot disease, which may prevent complications in high-risk patients with diabetes. PMID- 22067284 TI - Genome protective effect of metformin as revealed by reduced level of constitutive DNA damage signaling. AB - We have shown before that constitutive DNA damage signaling represented by H2AX Ser139 phosphorylation and ATM activation in untreated normal and tumor cells is a reporter of the persistent DNA replication stress induced by endogenous oxidants, the by-products of aerobic respiration. In the present study we observed that exposure of normal mitogenically stimulated lymphocytes or tumor cell lines A549, TK6 and A431 to metformin, the specific activator of 5'AMP activated protein kinase (AMPK) and an inhibitor of mTOR signaling, resulted in attenuation of constitutive H2AX phosphorylation and ATM activation. The effects were metformin-concentration dependent and seen even at the pharmacologically pertinent 0.1 mM drug concentration. The data also show that intracellular levels of endogenous reactive oxidants able to oxidize 2',7'-dihydro-dichlorofluorescein diacetate was reduced in metformin-treated cells. Since persistent constitutive DNA replication stress, particularly when paralleled by mTOR signaling, is considered to be the major cause of aging, the present findings are consistent with the notion that metformin, by reducing both DNA replication stress and mTOR signaling, slows down aging and/or cell senescence processes. PMID- 22067286 TI - Development of a remote monitoring satisfaction survey and its use in a clinical trial with lung transplant recipients. AB - We developed an instrument to measure the satisfaction of lung transplant recipients with home monitoring. The survey comprised 15 items, each scored on a five-point Likert-type scale (from strongly disagree to strongly agree). Three additional free-text items enabled subjects to provide comments. The survey had a scoring range of 15-75. In a test group of 43 patients, the internal consistency (Cronbach's alpha) was 0.93 overall for all questions. The intra-class correlation for scores from the same 27 patients approximately 2.5 months apart was 0.77 for the total score. The survey was used to evaluate subject satisfaction in a randomized controlled trial of a computerized algorithm for triaging lung transplant recipients. Surveys were mailed to 50 study subjects and were returned by 32 (64% return rate). Ninety percent of respondents were satisfied with the home monitoring programme and would recommend it to other patients. PMID- 22067287 TI - Remote CT reading using an ultramobile PC and web-based remote viewing over a wireless network. AB - We developed a new type of mobile teleradiology system using an ultramobile PC (UMPC) for web-based remote viewing over a wireless network. We assessed the diagnostic performance of this system for abdominal CT interpretation. Performance was compared with an emergency department clinical monitor using a DICOM viewer. A total of 100 abdominal CT examinations were presented to four observers. There were 56 examinations showing appendicitis and 44 which were normal. The observers viewed the images using a UMPC display and an LCD monitor and rated each examination on a five-point scale. Receiver operating characteristics (ROC) analysis was used to test for differences. The sensitivity and specificities of all observers were similarly high. The average area under the ROC curve for readings performed on the UMPC and the LCD monitor was 0.959 and 0.976, respectively. There were no significant differences between the two display systems for interpreting abdominal CTs. The web-based mobile teleradiology system appears to be feasible for reading abdominal CTs for diagnosing appendicitis and may be valuable in emergency teleconsultation. PMID- 22067288 TI - Sarcoglycans in the normal and pathological breast tissue of humans: an immunohistochemical and molecular study. AB - The sarcoglycan complex, consisting of alpha-, beta-, gamma-, delta- and epsilon sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of alpha- and gamma-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only beta-, delta-, and epsilon-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant. PMID- 22067289 TI - Medial prefrontal cortical activation during working memory differentiates schizophrenia and bipolar psychotic patients: a pilot fMRI study Response to the comment. PMID- 22067290 TI - Learning and perceptual similarity among cuticular hydrocarbons in ants. AB - Nestmate recognition in ants is based on perceived differences in a multi component blend of hydrocarbons that are present on the insect cuticle. Although supplementation experiments have shown that some classes of hydrocarbons, such as methyl branched alkanes and alkenes, have a salient role in nestmate recognition, there was basically no information available on how ants detect and perceive these molecules. We used a new conditioning procedure to investigate whether individual carpenter ants could associate a given hydrocarbon (linear or methyl branched alkane) to sugar reward. We then studied perceptual similarity between a hydrocarbon previously associated with sugar and a novel hydrocarbon. Ants learnt all hydrocarbon-reward associations rapidly and with the same efficiency, regardless of the structure of the molecules. Ants could discriminate among a large number of pairs of hydrocarbons, but also generalised. Generalisation depended both on the structure of the molecule and the animal's experience. For linear alkanes, generalisation was observed when the novel molecule was smaller than the conditioned one. Generalisation between pairs of methyl-alkanes was high, while generalisation between hydrocarbons that differed in the presence or absence of a methyl group was low, suggesting that chain length and functional group might be coded independently by the ant olfactory system. Understanding variations in perception of recognition cues in ants is necessary for the general understanding of the mechanisms involved in social recognition processes based on chemical cues. PMID- 22067291 TI - Attraction of Drosophila melanogaster males to food-related and fly odours. AB - The fruit fly Drosophila melanogaster has become a model for olfaction and odour mediated behaviour. In the wild, Drosophila flies aggregate on decaying fruit where they mate and oviposit and a strategy to find mates would be to locate fruit which has already been colonized by other flies. We therefore developed a bioassay to investigate attraction of males to food and fly odours. We showed that upwind flights are initiated by food odours. At shorter distances, males are attracted by volatiles produced by conspecifics. However, only odours produced by copulating flies attract males. This suggests either a synergistic effect of both male and female odours or changes in pheromone release during mating, that indicate the presence of sexually receptive females. Our findings demonstrate the essential role of food odours and pheromones for mate location in D. melanogaster. PMID- 22067292 TI - Improved GART neural network model for pattern classification and rule extraction with application to power systems. AB - Generalized adaptive resonance theory (GART) is a neural network model that is capable of online learning and is effective in tackling pattern classification tasks. In this paper, we propose an improved GART model (IGART), and demonstrate its applicability to power systems. IGART enhances the dynamics of GART in several aspects, which include the use of the Laplacian likelihood function, a new vigilance function, a new match-tracking mechanism, an ordering algorithm for determining the sequence of training data, and a rule extraction capability to elicit if-then rules from the network. To assess the effectiveness of IGART and to compare its performances with those from other methods, three datasets that are related to power systems are employed. The experimental results demonstrate the usefulness of IGART with the rule extraction capability in undertaking classification problems in power systems engineering. PMID- 22067293 TI - Hepatoprotective potential of polyphenol rich extract of Murraya koenigii L.: an in vivo study. AB - The present study investigates hepatoprotective effects of polyphenol rich Murraya koenigii L. (MK) hydro-ethanolic leaf extract in CCl(4) treated hepatotoxic rats. Plasma markers of hepatic damage, lipid peroxidation levels, enzymatic, and non-enzymatic antioxidants in liver and histopathological changes were investigated in control and treated rats. MK pretreated rats with different doses (200, 400 and 600mg/kg body weight) showed significant decrement in activity levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and bilirubin. Also, MK treated rats recorded a dose dependent increment in hepatic super oxide dismutase, catalase, reduced glutathione and ascorbic acid and, a decrement in lipid peroxidation. Microscopic evaluations of liver revealed CCl(4)-induced lesions and related toxic manifestations that were minimal in liver of rats pretreated with MK extract. These results demonstrate that hydro-ethanolic leaf extract of MK possesses hepatoprotective potentials. PMID- 22067294 TI - Evaluation of antioxidative, protective effect against H2O2 induced cytotoxicity, and cytotoxic activities of three different Quercus species. AB - Quercus species are used as antidiarrheic, for the treatment of hemorrhoid, oral and anal mucosa inflammation. These tree species have been of interest to researchers because of their usage in folk medicine, consumption as food, beverage and especially usage of oak woods for construction in wine barrels. The DPPH, SO and NO radical scavenging activities, protective effect against H2O2 induced cytotoxicity as well as their cytotoxic activity against Hep-2 human larynx epidermoid carcinoma cell line of the MeOH and water extracts of the barks of Quercus cerris var. cerris, Quercusmacranthera subsp. syspirensis and Quercus aucheri were investigated for the first time. Total phenolic content of the extracts was also evaluated by Folin-Ciocalteu method. Results demonstrated that the extracts showed strong radical scavenging activity comparable to those of standard compounds. Extracts also showed good protective effect against H2O2 induced cytotoxicity on human erythrocytes comparing to ascorbic acid. On the other hand, while each extract showed dose dependent cytotoxic activity, MeOH extract of Q.macranthera subsp. syspirensis showed the strongest cytotoxicity against the tested cell line. Taken together, the results showed that Quercus species may be a promising alternative to synthetic substances as natural compound with high antioxidant and antiproliferative activities. PMID- 22067295 TI - Reliability, construct validity and measurement potential of the ICF comprehensive core set for osteoarthritis. AB - BACKGROUND: This study aimed to investigate the reliability and construct validity of the International Classification of Functioning, Disability and Health (ICF) Comprehensive Core Set for osteoarthritis (OA) in order to test its possible use as a measuring tool for functioning. METHODS: 100 patients with OA (84 F, 16 M; mean age 63 yr) completed forms including demographic and clinical information besides the Short Form (36) Health Survey (SF-36(r)) and the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC). The ICF Comprehensive Core Set for OA was filled by health professionals. The internal construct validities of "Body Functions-Body structures" (BF-BS), "Activity" (A), "Participation" (P) and "Environmental Factors" (EF) domains were tested by Rasch analysis and reliability by internal consistency and person separation index (PSI). External construct validity was evaluated by correlating the Rasch transformed scores with SF-36 and WOMAC. RESULTS: In each scale, some items showing disordered thresholds were rescored, testlets were created to overcome the problem of local dependency and items that did not fit to the Rasch model were deleted. The internal construct validity of the four scales (BF-BS 16 items, A 8 items, P 7 items, EF 13 items) were good [mean item fit (SD) 0.138 (0.921), 0.216 (1.237), 0.759 (0.986) and -0.079 (2.200); person item fit (SD) -0.147 (0.652), -0.241 (0.894), -0.310 (1.187) and -0.491 (1.173) respectively], indicating a single underlying construct for each scale. The scales were free of differential item functioning (DIF) for age, gender, years of education and duration of disease. Reliabilities of the BF-BS, A, P, and EF scales were good with Cronbach's alphas of 0.79, 0.86, 0.88, and 0.83 and PSI's of 0.76, 0.86, 0.87, and 0.71, respectively. Rasch scores of BF-BS, A, and P showed moderate correlations with SF-36 and WOMAC scores where the EF had significant but weak correlations only with SF36-Social Functioning and SF36-Mental Health. CONCLUSION: Since the four different scales derived from BF-BS, A, P, and EF components of the ICF core set for OA were shown to be valid and reliable through a combination of Rasch analysis and classical psychometric methods, these might be used as clinical assessment tools. PMID- 22067296 TI - Is sparing the pronator quadratus muscle possible in volar plating of the distal radius? AB - We measured the length of the distal radius that can be exposed by mobilizing the distal edge of pronator quadratus (PQ) without detaching its radial attachment. Measurements were made in 20 cadaveric upper limbs from the distal margin of the radius in line with the scaphoid and lunate fossae to the distal margin of the PQ, before and after mobilization of the muscle from its distal attachment. The mean distance from the distal edge of the PQ to the scaphoid fossa was 13.1 mm and to the lunate fossa was 10.7 mm. This increased to a mean of 26.2 mm for the scaphoid and a mean of 23.8 mm for the lunate fossa following mobilization of PQ. Subperiosteal retrograde release of the PQ from its distal margin will allow for the placement of a volar plate and insertion of locking peri-articular screws in the great majority of volar locking plate systems on the market. PMID- 22067297 TI - Kienbock's disease: percutaneous cement lunatoplasty--a cadaver study. PMID- 22067298 TI - Outcome of nerve transfers for traumatic complete brachial plexus avulsion: results of 28 patients by DASH and NRS questionnaires. AB - The objective of this study was to evaluate outcomes of patients who suffered complete brachial plexus avulsion before and after nerve transfers by assessing upper extremity function and pain using the DASH and NRS questionnaires. Patients who underwent nerve transfers improved their DASH and NRS scores compared with before surgery. Although individually there was no correlation with improved scores, the triple combination of rehabilitation exercises, electrical stimulation therapy and neurotrophic drugs postoperatively correlated positively with improved functional outcomes. This study suggested a positive effect of the passage of time and nerve transfers in total brachial plexus avulsions from patients' self assessments. PMID- 22067299 TI - Scanning electron microscopy analysis of erythrocytes in thromboembolic ischemic stroke. AB - INTRODUCTION: Erythrocytes play an important role in hemostasis and disease conditions. During ischemic stroke, erythrocytes undergo oxidative and proteolytic changes resulting in a changed cellular rheology. METHODS: Blood samples were obtained from controls and thromboembolic ischemic stroke patients (within 48 h of stroke). The ultrastructure of erythrocytes was compared, using a scanning electron microscope (SEM). Abnormal morphology included codocytes, knizocytes, stomatocytes, and echinocytes. Percentage of abnormal cells was calculated, and the analyses were performed using the statistical program NCSS with the level of significance set at 0.05. A t-test was carried out to compare the data from the erythrocyte counts of stroke patients with that of the control subjects. RESULTS: Ultrastructural SEM results showed that there are a large percentage of erythrocytes in healthy individuals that do not have a typical discoid shape, when studying the cells using a high magnification electron microscope. Furthermore, analysis showed that variation in shape is so subtle that it is not clearly visible using a typical light microscopy blood smear analysis. Thromboembolic ischemic stroke patients presented with a significant amount of erythrocytes with abnormal morphology. CONCLUSION: We suggest that in healthy individuals, a typical smear would contain several nondiscoid-shaped erythrocytes, only clearly visible at high magnification. However, thromboembolic ischemic stroke does significantly impact erythorcyte shape, and this change in morphology may result in an impaired microcirculation, as well as impaired oxygen carrying capacity. This changed morphology may further complicate the restoring of homeostasis caused by acute thromboembolic stroke. PMID- 22067300 TI - Freshwater ascomycetes: Natipusillaceae, a new family of tropical fungi, including Natipusilla bellaspora sp. nov. from the Peruvian Amazon. AB - A new ascomycete species, Natipusilla bellaspora, collected from submerged woody debris in a freshwater stream at Los Amigos Biological Station, Madre De Dios in the Peruvian Amazon is described and illustrated. This fungus is characterized by small, globose to subglobose, hyaline ascomata; small, globose to subglobose, eight-spored fissitunicate asci; one-septate, multiguttulate ascospores with two different gelatinous sheaths, an outer amorphous sheath that enlarges in water and an inner sheath that has a distinctive persistent shape and is attached to the ascospore apex. Morphologically N. bellaspora differs from other Natipusilla species in having larger ascospores and two ascospore sheaths. A second Natipusilla species, N. limonensis, is reported for the first time from Peru. Based on the unique morphological characters of taxa in Natipusilla and results of previous molecular phylogenetic analyses with other members of the Dothideomycetes, we establish Natipusillaceae fam. nov. for this unique tropical freshwater clade. PMID- 22067301 TI - Fine-scale mapping in Neurospora crassa by using genome-wide knockout strains. AB - Fine-scale genetic mapping is often hindered by the lack of adequate markers surrounding the locus of interest. In the filamentous ascomycete Neurospora crassa, the genome has been sequenced and an effort has been made to generate genome-wide deletion strains for the entire gene set. Accordingly, the hygromycin resistant marker in each deletion strain can be used as a mapping locus in a classical three-point cross, along with the mapping target and a standard marker. We have demonstrated the feasibility of this fine-scale mapping approach in N. crassa by refining the location of r(Sk-2). PMID- 22067302 TI - Characterization of a Basidiomycete fungus from stored sugar beet roots. AB - Eighteen isolates from sugar beet roots associated with an unknown etiology were characterized based on observations of morphological characters, hyphal growth at 4-28 C, production of phenol oxidases and sequence analysis of internal transcribed spacer (ITS) and large subunit (LSU) regions of the ribosomal DNA (rDNA). The isolates did not produce asexual or sexual spores, had binucleate hyphal cells with clamp connections, grew 4-22 C with estimated optimal growth at 14.5 C and formed a dark brown pigment on potato dextrose or malt extract agar amended with 0.5% tannic acid. Color changes observed when solutions of gum guiac, guiacol and syringaldzine were applied directly to mycelium grown on these media indicated that all isolates produced phenol oxidases. Sequences of ITS and LSU regions on the rDNA gene from 15 isolates were 99.2-100% identical, and analysis of sequence data with maximum likelihood and maximum parsimony suggest that the isolates from sugar beet roots are phylogenetically related to Athelia bombacina, Granulobasidium vellereum and Cyphella digitalis. High statistical support for both loci under different criteria confirmed that Athelia bombacina was consistently the closest known relative to the sugar beet isolates. Additional taxonomic investigations are needed before species can be clarified and designated for these isolates. PMID- 22067303 TI - Phialide arrangement and character evolution in the helotialean anamorph genera Cadophora and Phialocephala. AB - The dematiaceous hyphomycete genera Cadophora and Phialocephala are anamorphs associated with mollisioid inoperculate discomycetes (Helotiales) and are delineated based on the complexity of the phialide arrangement with members of Cadophora producing solitary phialides and species of Phialocephala producing complex heads of multiple phialides. A third phylogenetically related taxon, Leptodontidium orchidicola, produces mostly indehiscent conidia that may represent non-functional phialides. Morphological characteristics of both sexual and asexual states of these and other fungi in a focal group of helotialean taxa were re-examined, in light of relationships shown by molecular phylogenetic analyses of rDNA ITS sequences, to determine the evolutionary significance of phialide arrangement. The focal species of Phialocephala formed a monophyletic clade, while five of six species of Cadophora including the type were in a separate clade along with L. orchidicola. C. finlandica was placed in a third clade with species of Meliniomyces and Rhizoscyphus. We hypothesized that the ancestral state for species in Cadophora and Phialocephala is the production of sclerotium-like heads of multiple phialides, which has been retained in most species assignable to Phialocephala. A reduction to solitary phialides occurred in the lineage leading to the clade containing most of the Cadophora species. Two possible reductions to non-functional phialides were identified: one in the Meliniomyces-C. finlandica-Chloridium paucisporum clade and another in the L. orchidicola and Mollisia "rhizophila": clade. A reversion to increased phialide complexity might have occurred in the clade containing C. finlandica and Ch. paucisporum. Our data and analyses also show a previously unrecognized relationship between teleomorph and anamorph morphology in that Mollisia species with smaller asci would be expected to have Phialocephala states while those with larger asci would be expected to have Cadophora states. Based on morphology and phylogenetic placement, L. orchidicola and C. hiberna are transferred respectively to Cadophora and Phialocephala. PMID- 22067304 TI - New teleomorph combinations in the entomopathogenic genus Metacordyceps. AB - The genus Metacordyceps contains arthropod pathogens in Clavicipitaceae (Hypocreales) that formerly were classified in Cordyceps sensu Kobayasi et Mains. Of the current arthropod pathogenic genera of Hypocreales, the genus Metacordyceps remains one of the most poorly understood and contains a number of teleomorphic morphologies convergent with species of Cordyceps s.s. (Cordycipitaceae) and Ophiocordyceps (Ophiocordycipitaceae). Of note, the anamorph genera Metarhizium and Pochonia were found to be associated only with Metacordyceps and demonstrated to be phylogenetically informative for the clade. Several species of Cordyceps considered to have uncertain placements (incertae sedis) in the current taxonomic framework of clavicipitoid fungi were collected during field expeditions mostly in eastern Asia. Species reclassified here in Metacordyceps include Cordyceps atrovirens Kobayasi & Shimizu, Cordyceps indigotica Kobayasi & Shimizu, Cordyceps khaoyaiensis Hywel-Jones, Cordyceps kusanagiensis Kobayasi & Shimizu, Cordyceps martialis Speg., Ophiocordyceps owariensis Kobayasi, Cordyceps pseudoatrovirens Kobayasi & Shimizu and Ophicordyceps owariensis f. viridescens (Uchiy. & Udagawa) G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora. Incorporation of these species in a multigene phylogenetic framework of the major clades of clavicipitoid fungi more than doubled the number of species in Metacordyceps and allowed for refinement of morphological concepts for the genus consistent with the phylogenetic structure. Based on these findings we then discuss evolution of this genus, subgeneric relationships, anamorph connections, and suggest additional species that should be confirmed for possible inclusion in Metacordyceps. PMID- 22067305 TI - Sequestrate species of Agaricus and Macrolepiota from Australia: new species and combinations and their position in a calibrated phylogeny. AB - Australian collections of sequestrate Agaricaceae were examined with morphological and molecular data (nuclear DNA from ITS and LSU), and the majority were found to belong to the genera Agaricus and Macrolepiota. Previously described Australian species of Endoptychum are transferred to the appropriate agaricoid genera and several new combinations proposed. Descriptions and illustrations are provided for these and eight new species: Agaricus eburneocanus sp. nov., A. chartaceus sp. nov., A. erythrosarx sp. nov., A. inilleasper sp. nov., A. pachydermus sp. nov., Macrolepiota gasteroidea sp. nov., M. vinaceofibrillosa sp. nov. and M. turbinata sp. nov. The sequestrate genus Barcheria is retained as a distinct taxon. Timing of evolution of sequestrate sporocarp forms in Macrolepiota, Chlorophyllum and Agaricus seems to have occurred in the past 15 000 000 y, and a stem age is approximately 65 000 000 y for Barcheria. PMID- 22067306 TI - New species of Clavulina (Cantharellales, Basidiomycota) with resupinate and effused basidiomata from the Guiana Shield. AB - Three new species of Clavulina (Cantharellales, Basidiomycota) are described from rainforests dominated by ectomycorrhizal trees of the leguminous genus Dicymbe (Fabaceae subfam. Caesalpinioideae) from the central Guiana Shield. Species of Clavulina typically form branched, coralloid basidiomata with amphigenous hymenia. However, the three species described here form resupinate or effuso coralloid basidiomata, macromorphological forms previously unknown in Clavulina. Macromorphological, micromorphological, habitat and DNA sequence data are provided for each new species. Micromorphological features and DNA sequence data from the second largest subunit of DNA-dependant RNA polymerase II (rpb2) and internal transcribed spacer (ITS) and large subunit (28S) of the ribosomal repeat justify placement of these new species in Clavulina. Comparisons with described Clavulina species and other resupinate taxa within the Cantharellales are provided. PMID- 22067307 TI - The treatment of neuroendocrine tumors with long-acting somatostatin analogs: a single center experience with lanreotide autogel. AB - The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated. PMID- 22067308 TI - Current status of pediatric intestinal failure, rehabilitation, and transplantation: summary of a colloquium. AB - An international symposium convened September 9-11, 2010, in Chicago to present the state of the art and science of the multidisciplinary care of intestinal failure in children. Medical and surgical management of the child with intestinal failure was presented with a focus on the importance of multidisciplinary intestinal failure management. Issues of timing of referral and benefit risk analysis for intestine "rehabilitation" and transplant were presented. Areas of opportunity such as increased donor recovery, improvement of long-term transplant outcomes, optimization of immune monitoring, and quality-of-life outcomes were reviewed. PMID- 22067309 TI - Donor desmopressin is associated with superior graft survival after kidney transplantation. AB - BACKGROUND: A recent randomized trial showed that pretreatment of the brain-dead donor with low-dose dopamine improves immediate kidney graft function, by limiting injury from cold storage (ClinicalTrials.gov Identifier: NCT00115115). This study determines whether donor exposure to desmopressin (1-deamino-8-d arginine-vasopressin [DDAVP]) before organ retrieval affects renal transplant outcome. METHODS: This retrospective multicenter cohort study, nested in the database of the dopamine trial, includes 264 deceased heart-beating donors with confirmed brain death and corresponding 487 renal allograft recipients transplanted at 60 European centers between March 2004 and August 2007. We assessed differences in delayed graft function, biopsy-proven acute rejections, and 2-year kidney graft survival in recipients of a DDAVP-exposed versus unexposed graft. RESULTS: DDAVP was associated with improved graft survival (85.4% vs. 73.6%, P=0.003). This survival benefit persisted after censoring for death with functioning graft (91.1% vs. 82.0%, P=0.01) and after adjustment for confounders including covariate adjustment from propensity scoring (hazard ratio 0.40, 95% confidence interval [CI] 0.21-0.77; P=0.006). Delayed graft function (odds ratio 0.97, 95% CI 0.57-1.65; P=0.92) and biopsy-proven acute rejections (odds ratio 1.32, 95% CI 0.70-2.49; P=0.40) were unaffected. The survival effect was enhanced after a shorter cold ischemic time less than 14 hr (91.3% vs. 77.8%, P=0.008) and after dopamine pretreatment (92.7% vs. 78.6%, P=0.006). By contrast, prolonged cold ischemic time more than or equal to 14 hr (91.2% vs. 86.5%, P=0.39) and assignment to the nondopamine group (89.7% vs. 84.8%, P=0.37) abrogated the survival advantage. CONCLUSIONS: Donor DDAVP seems to improve renal allograft survival. Combined use of donor DDAVP and low-dose dopamine should receive further evaluation. PMID- 22067310 TI - Islet graft survival and function: concomitant culture and transplantation with vascular endothelial cells in diabetic rats. AB - BACKGROUND: Human islet transplantation is a great potential therapy for type I diabetes. To investigate islet graft survival and function, we recently showed the improved effects after co-culture and co-transplantation with vascular endothelial cells (ECs) in diabetic rats. METHODS: ECs were isolated, and the viability of isolated islets was assessed in two groups (standard culture group and co-culture group with ECs). Then streptozotocin-induced diabetic rats were divided into four groups before islet transplantation as follows: group A with infusion of islet grafts; group B with combined vascular ECs and islet grafts; groups C and D as controls with single ECs infusion and phosphate-buffered saline injection, respectively. Blood glucose and insulin concentrations were measured daily. Expression of vascular endothelial growth factor was investigated by immunohistochemical staining. The mean microvascular density was also calculated. RESULTS: More than 90% of acridine orange-propidium iodide staining positive islets demonstrated normal morphology while co-cultured with ECs for 7 days. Compared with standard control, insulin release assays showed a significantly higher simulation index in co-culture group except for the first day (P<0.05). After transplantation, there was a significant difference in concentrations of blood glucose and insulin among these groups after 3 days (P<0.05). The mean microvascular density in co-culture group was significantly higher than that in single islet group (P=0.04). CONCLUSION: Co-culture with ECs in vitro could improve the survival and function of isolated rat islet, and co-transplantation of islets with ECs could effectively prolong the islet graft survival in diabetic rats. PMID- 22067311 TI - Early changes in kidney function predict long-term chronic kidney disease and mortality in patients after liver transplantation. AB - BACKGROUND: Chronic kidney disease (CKD) is a well-known complication after liver transplantation (LT) and is associated with increased mortality. The purpose of this study was to determine risk factors of advanced CKD and mortality after LT. METHODS: Four hundred forty-five adult patients underwent LT between June 1990 and September 2007 and survived more than 1 month. Multivariate Cox regression analyses were performed for time to CKD stage 4 (glomerular filtration rate [GFR] <=30 mL/min), time to chronic dialysis, and all-cause mortality. Several patient and disease characteristics were used as independent pre- and posttransplant variables. We specifically analyzed a drop more than or equal to 30% in the estimated GFR (eGFR) during the first year posttransplant. RESULTS: Diabetes mellitus pretransplant and a drop more than or equal to 30% in the eGFR between 3 and 12 months predicted CKD stage 4 (odds ratio [OR] 4.1, 95% confidence interval [CI] 1.9-5.4, P<0.001 and OR 16.1, 95% CI 5.9-44.5, P<0.0001, respectively), the need for chronic dialysis (OR 3.8, 95% CI 1.1-13.2, P=0.03 and OR 14.6, 95% CI 3.0-71.4, P<0.001, respectively), and all-cause mortality (OR 1.9, 95% CI 1.2 2.9, P=0.004 and OR 2.6, 95% CI 1.6-4.4, P<0.001, respectively), more than 1 year after LT. CONCLUSIONS: Diabetes mellitus pretransplant and a drop more than or equal to 30% in the eGFR within the first year are strong predictors of advanced CKD, chronic dialysis, and death more than 1 year after LT. These easily determined clinical variables define a population at risk for CKD who should be targeted for renal protection strategies. PMID- 22067312 TI - Early steroid withdrawal and optimization of mycophenolic acid exposure in kidney transplant recipients receiving mycophenolate mofetil. AB - BACKGROUND: Early posttransplant steroid withdrawal may increase the risk of acute rejection and the occurrence of subclinical acute rejection (SCAR). We assessed the feasibility and safety of early steroid withdrawal in low-risk patients receiving cyclosporine A (CsA) and the impact of optimization of mycophenolic acid exposure on steroid withdrawal success. METHODS: De novo, low immunological risk kidney recipients received an anti-interleukin-2-receptor alpha antibody induction, a short course of 7 days of corticosteroids, and CsA with 2-hr postdose concentration monitoring. They were randomized to adjusted dose (AD) of mycophenolate mofetil (MMF) using therapeutic drug monitoring (TDM) or a fixed-dose (FD) regimen. MMF 3 g was initiated posttransplant and then adjusted starting at week 2 to a 0 to 12 hr area under the concentration time curve of 40 mg . h/L versus 2 g daily, respectively. The primary endpoint was a composite of the proportion of patients experiencing biopsy-proven acute rejection (BPAR) and those with SCAR identified on the 3-month protocol biopsy. RESULTS: Among 247 analyzed patients, only 22 in the AD group and 17 in the FD group experienced BPAR or SCAR (P=0.46). The rate of SCAR was low: 4% (AD) and 2.5% (FD). No between-group difference in the incidence of BPAR was observed. TDM yielded MMF doses ranging from 1 to 4 g/d and significantly reduced interpatient variability at weeks 26 and 52 in the AD group. CONCLUSIONS: In low-immunological risk kidney recipients, MMF combined with CsA allows early corticosteroid discontinuation with good tolerability. In this group of patients, TDM of MMF does not improve clinical outcome. PMID- 22067313 TI - Innominate vein vascular ring provides novel insight into systemic venous embryogenesis. AB - Anomalies of the innominate vein are uncommon in congenital cardiac disease. We report a case of duplicate innominate veins forming a vascular ring encircling the ascending aorta. We postulate that this vascular ring represents the failure of both a dorsal and ventral precardinal anastomosis to regress. PMID- 22067314 TI - TGF-beta mediates suppression of adipogenesis by estradiol through connective tissue growth factor induction. AB - In the bone marrow cavity, adipocyte numbers increase, whereas osteoblast progenitor numbers decrease with aging. Because adipocytes and osteoblasts share a common progenitor, it is possible that this shift is due to an increase in adipocyte-lineage cells at the expense of osteoblast-lineage commitment. Estrogens inhibit adipocyte differentiation, and in both men and women, circulating estrogens correlate with bone loss with aging. In bone cells, estrogens stimulate expression of TGF-beta and suppress mesenchymal cell adipogenesis. Using a tripotential mesenchymal cell line, we have examined whether estradiol suppression of adipocyte differentiation is due to stimulation of TGF-beta and the mechanism by which TGF-beta suppresses adipogenesis. We observed that estradiol-mediated suppression of adipogenic gene expression required at least 48 h treatment. TGF-beta expression increased within 24 h of estradiol treatment, and TGF-beta inhibition reversed estradiol influences on adipogenesis and adipocyte gene expression. Connective tissue growth factor (CTGF) mediates TGF-beta suppression of adipogenesis in mouse 3T3-L1 cells. CTGF expression was induced within 24 h of TGF-beta treatment, whereas estradiol mediated induction required 48 h treatment. Moreover, estradiol-mediated induction of CTGF was abrogated by TGF-beta inhibition. These data support that estradiol effects on adipogenesis involves TGF-beta induction, which then induces CTGF to suppress adipogenesis. PMID- 22067316 TI - Neural distribution of vasotocin receptor mRNA in two species of songbird. AB - The neurohypophyseal hormones vasopressin and oxytocin are produced and released within the mammalian brain, where they act via multiple receptor subtypes. The neural distributions of these receptors, for example, V1a and oxytocin receptors, have been well described in many mammals. In birds, the distribution of binding sites for the homologous neuropeptides, vasotocin (VT) and mesotocin, has been studied in several species by using synthetic radioligands designed to bind to mammalian receptors. Such binding studies, however, may not reveal the specific distributions of each receptor subtype. To identify and map the receptors likely to bind VT and mesotocin, we generated partial cDNA sequences for four VT receptor subtypes, VT1, VT2 (V1b), VT3 (oxytocin-like), and VT4 (V1a), in white throated sparrow (Zonotrichia albicollis) and zebra finch (Taeniopygia guttata). These genes shared high sequence identity with the homologous avian and mammalian neurohypophyseal peptide receptors, and we found evidence for VT1, VT3, and VT4 receptor mRNA expression throughout the brains of both species. As has been described in rodents, there was striking interspecific and intraspecific variation in the densities and distribution of these receptors. For example, whereas the VT1 receptor mRNA was more widespread in zebra finch brain, the VT3 (oxytocin-like) receptor mRNA was more prevalent in the sparrow brain. Although VT2 (V1b) receptor mRNA was abundant in the pituitary, it was not found in the brain. Because of their association with brain regions implicated in social behavior, the VT1, VT3, and VT4 receptors are all likely candidates for mediating the behavioral effects of VT. PMID- 22067315 TI - Type 2 corticotropin-releasing factor receptor in the ventromedial nucleus of hypothalamus is critical in regulating feeding and lipid metabolism in white adipose tissue. AB - Ventromedial nucleus of hypothalamus (VMH) plays a critical role in regulating feeding and energy metabolism. The nucleus expresses high levels of the type 2 corticotropin-releasing factor receptor (CRFR2) and receives prominent innervation of nerve fibers containing Urocortin 3 (Ucn 3), an endogenous ligand of the receptor. In the present study, we showed that mice deficient in Ucn 3 had elevated basal feeding and increased nocturnal food intake after overnight fasting compared with the wild-type (WT) littermates. The Ucn 3 null mice also had lower circulating insulin levels compared with those of the WT mice. Interestingly, the mutant mice maintained a comparable body weight with the WT littermates. Mice with reduced CRFR2 expression in the VMH by small hairpin RNA knockdown (KD) recapitulated feeding phenotypes observed in the Ucn 3 null mice. However, VMH CRFR2 KD mice gained significantly more weight than control mice. The weight gain was due to an accumulation of white adipose tissue (WAT) accompanied by reduced plasma free fatty acids and glycerol levels, increased respiratory quotients, and improved glucose tolerance. On the other hand, plasma insulin levels were comparable with the receptor KD and control mice. Furthermore, the expression of several genes, including hormone-sensitive lipase, was significantly reduced in the WAT of VMH CRFR2 KD mice compared with controls. These results indicate that Ucn 3 signaling through CRFR2 is a critical molecular mediator in the VMH in regulating feeding and lipid metabolism in WAT. PMID- 22067317 TI - Lack of overt FGF21 resistance in two mouse models of obesity and insulin resistance. AB - Circulating levels of fibroblast growth factor 21 (FGF21), a metabolic regulator of glucose, lipid, and energy homeostasis, are elevated in obese diabetic subjects, raising questions about potential FGF21 resistance. Here we report tissue expression changes in FGF21 and its receptor components, and we describe the target-organ and whole-body responses to FGF21 in ob/ob and diet-induced obese (DIO) mice. Plasma FGF21 concentrations were elevated 8- and 16-fold in DIO and ob/ob mice, respectively, paralleling a dramatic increase in hepatic FGF21 mRNA expression. Concurrently, expression levels of betaKlotho, FGF receptor (FGFR)-1c, and FGFR2c were markedly down-regulated in the white adipose tissues (WAT) of ob/ob and DIO mice. However, dose-response curves of recombinant human FGF21 (rhFGF21) stimulation of ERK phosphorylation in the liver and WAT were not right shifted in disease models, although the magnitude of induction in ERK phosphorylation was partially attenuated in DIO mice. Whole-body metabolic responses were preserved in ob/ob and DIO mice, with disease models being more sensitive and responsive than lean mice to the glucose-lowering and weight-loss effects of rhFGF21. Endogenous FGF21 levels, although elevated in diseased mice, were below the half-maximal effective concentrations of rhFGF21, suggesting a state of relative deficiency. Hepatic and WAT FGF21 mRNA expression levels declined after rhFGF21 treatment in the absence of the increased expression levels of betaKlotho and FGFR. We conclude that overt FGF21 resistance was not evident in the disease models, and increased hepatic FGF21 expression as a result of local metabolic changes is likely a major cause of elevated circulating FGF21 levels. PMID- 22067318 TI - 11beta-Hydroxysteroid dehydrogenase type 1, but not type 2, deficiency worsens acute inflammation and experimental arthritis in mice. AB - Glucocorticoids profoundly influence immune responses, and synthetic glucocorticoids are widely used clinically for their potent antiinflammatory effects. Endogenous glucocorticoid action is modulated by the two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). In vivo, 11beta-HSD1 catalyzes the reduction of inactive cortisone or 11-dehydrocorticosterone into active cortisol or corticosterone, respectively, thereby increasing intracellular glucocorticoid levels. 11beta-HSD2 catalyzes the reverse reaction, inactivating intracellular glucocorticoids. Both enzymes have been postulated to modulate inflammatory responses. In the K/BxN serum transfer model of arthritis, 11beta HSD1-deficient mice showed earlier onset and slower resolution of inflammation than wild-type controls, with greater exostoses in periarticular bone and, uniquely, ganglion cysts, consistent with greater inflammation. In contrast, K/BxN serum arthritis was unaffected by 11beta-HSD2 deficiency. In a distinct model of inflammation, thioglycollate-induced sterile peritonitis, 11beta-HSD1 deficient mice had more inflammatory cells in the peritoneum, but again 11beta HSD2-deficient mice did not differ from controls. Additionally, compared with control mice, 11beta-HSD1-deficient mice showed greater numbers of inflammatory cells in pleural lavages in carrageenan-induced pleurisy with lung pathology consistent with slower resolution. These data suggest that 11beta-HSD1 limits acute inflammation. In contrast, 11beta-HSD2 plays no role in acute inflammatory responses in mice. Regulation of local 11beta-HSD1 expression and/or delivery of substrate may afford a novel approach for antiinflammatory therapy. PMID- 22067319 TI - Role of IGFBP-3 in the regulation of beta-cell mass during obesity: adipose tissue/beta-cell cross talk. AB - In obesity an increase in beta-cell mass occurs to cope with the rise in insulin demand. This beta-cell plasticity is essential to avoid the onset of hyperglycemia, although the molecular mechanisms that regulate this process remain unclear. This study analyzed the role of adipose tissue in the control of beta-cell replication. Using a diet-induced model of obesity, we obtained conditioned media from three different white adipose tissue depots. Only in the adipose tissue depot surrounding the pancreas did the diet induce changes that led to an increase in INS1E cells and the islet replication rate. To identify the factors responsible for this proliferative effect, adipose tissue gene expression analysis was conducted by microarrays and quantitative RT-PCR. Of all the differentially expressed proteins, only the secreted ones were studied. IGF binding protein 3 (Igfbp3) was identified as the candidate for this effect. Furthermore, in the conditioned media, although the blockage of IGFBP3 led to an increase in the proliferation rate, the blockage of IGF-I receptor decreased it. Taken together, these data show that obesity induces specific changes in the expression profile of the adipose tissue depot surrounding the pancreas, leading to a decrease in IGFBP3 secretion. This decrease acts in a paracrine manner, stimulating the beta-cell proliferation rate, probably through an IGF-I-dependent mechanism. This cross talk between the visceral-pancreatic adipose tissue and beta-cells is a novel mechanism that participates in the control of beta-cell plasticity. PMID- 22067320 TI - Identical gene regulation patterns of T3 and selective thyroid hormone receptor modulator GC-1. AB - Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRM) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver, and insulin resistance in preclinical animal models. STRM differ from native TH in preferential binding to the TRbeta subtype vs. TRalpha, increased uptake into liver, and reduced uptake into other tissues. However, selective modulators of other nuclear receptors exhibit important gene-selective actions, which are attributed to differential effects on receptor conformation and dynamics and can have profound influences in animals and humans. Although there are suggestions that STRM may exhibit such gene-specific actions, the extent to which they are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, T(3), and the prototype STRM GC-1 induce identical gene sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TRbeta, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency vs. T(3), at angiopoietin-like factor 4 in HepG2. Investigation of the latter effect confirms that GC-1 acts through TRbeta to directly induce this gene but this gene-selective activity is not related to unusual T(3)-response element sequence, unlike previously documented promoter selective STRM actions. Our data suggest that T(3) and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRM will be subtle and rare. PMID- 22067321 TI - Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice. AB - Kisspeptins (Kp), products of the Kiss1 gene that act via Gpr54 to potently stimulate GnRH secretion, operate as mediators of other regulatory signals of the gonadotropic axis. Mouse models of Gpr54 and/or Kiss1 inactivation have been used to address the contribution of Kp in the central control of gonadotropin secretion; yet, phenotypic and hormonal differences have been detected among the transgenic lines available. We report here a series of neuroendocrine analyses in male mice of a novel Gpr54 knockout (KO) model, generated by heterozygous crossing of a loxP-Gpr54/Protamine-Cre double mutant line. Gpr54-null males showed severe hypogonadotropic hypogonadism but retained robust responsiveness to GnRH. Gonadotropic responses to the agonist of ionotropic glutamate receptors, N methyl-d-aspartate, were attenuated, but persisted, in Gpr54-null mice. In contrast, LH secretion after activation of metabotropic glutamate receptors was totally preserved in the absence of Gpr54 signaling. Detectable, albeit reduced, LH responses were also observed in Gpr54 KO mice after intracerebroventricular administration of galanin-like peptide or RF9, putative antagonist of neuropeptide FF receptors for the mammalian ortholog of gonadotropin-inhibiting hormone. In contrast, the stimulatory effect of senktide, agonist of neurokinin B (NKB; cotransmitter of Kiss1 neurons), was totally abrogated in Gpr54 KO males. Lack of Kp signaling also eliminated feedback LH responses to testosterone withdrawal. However, residual but sustained increases of FSH were detected in gonadectomized Gpr54 KO males, in which testosterone replacement failed to fully suppress circulating FSH levels. In sum, our study provides novel evidence for the relative importance of Kp-dependent vs. -independent actions of several key regulators of GnRH secretion, such as glutamate, galanin-like peptide, and testosterone. In addition, our data document for the first time the indispensable role of Kp signaling in mediating the stimulatory effects of NKB on LH secretion, thus supporting the hypothesis that NKB actions on GnRH neurons are indirectly mediated via its ability to regulate Kiss1 neuronal output. PMID- 22067322 TI - Prenatal dexamethasone exposure potentiates diet-induced hepatosteatosis and decreases plasma IGF-I in a sex-specific fashion. AB - The clinical use of synthetic glucocorticoids in preterm infants to promote lung development has received considerable attention due to the potential for increased risk of developing metabolic disease in adulthood after such treatment. In this study, we examined the hypothesis that exposure to the synthetic glucocorticoid, dexamethasone (DEX), during late gestation in the rat results in the development of nonalcoholic fatty liver disease in adult offspring. Pregnant Sprague Dawley dams were treated with 0.4 mg/kg DEX beginning on gestational d 18 until parturition (gestational d 23). At postnatal d 21, offspring were weaned onto either a standard chow or high-fat (60% fat-derived calories) diet. In adulthood (postnatal d 60-65), hepatic tissue was harvested and examined for pathology. Liver steatosis, or fat accumulation, was found to be more severe in the DEX-exposed female offspring that were weaned onto the high-fat diet. This finding corresponded with decreased plasma IGF-I concentrations, as well as decreased hypothalamic expression of GHRH mRNA. Morphological measurements on body and long bone length further implicate a GH signaling deficit after fetal DEX exposure. Collectively, these data indicate suppression of GH axis function in the female DEX/high-fat cohort but not in the male offspring. Because deficits in the GH signaling can be linked to the development of nonalcoholic fatty liver disease, our results suggest that the prominent liver injury noted in female offspring exposed to DEX during late gestation may stem from abnormal development of the GH axis at the hypothalamic level. PMID- 22067323 TI - Mutual regulation of growth hormone and bone morphogenetic protein system in steroidogenesis by rat granulosa cells. AB - GH induces preantral follicle growth and differentiation with oocyte maturation. However, the effects of GH on ovarian steroidogenesis and the mechanisms underlying its effects have yet to be elucidated. In this study, we investigated the actions of GH on steroidogenesis by rat granulosa cells isolated from early antral follicles by focusing on the ovarian bone morphogenetic protein (BMP) system. We found that GH suppressed FSH-induced estradiol production with reduction in aromatase expression and, in contrast, GH increased FSH-induced progesterone level with induction of steroidogenic acute regulatory protein, side chain cleavage cytochrome P450, and 3beta-hydroxysteroid dehydrogenase. The effects of GH on steroidogenesis by granulosa cells were enhanced in the presence of the BMP antagonist noggin. Coculture of GH with oocytes did not alter GH regulation of steroidogenesis. Steroid production induced by cAMP donors was not affected by GH treatment and the GH effects on FSH-induced steroid production were not accompanied by changes in cAMP synthesis, suggesting that GH actions were not directly mediated by the cAMP-protein kinase A pathway. GH exerted synergistic effects on MAPK activation elicited by FSH, which regulated FSH induced steroidogenesis. In addition, GH-induced signal transducer and activator of transcription phosphorylation was involved in the induction of IGF-I expression. GH increased IGF-I, IGF-I receptor, and FSH receptor expression in granulosa cells, and inhibition of IGF-I signaling restored GH stimulation of FSH induced progesterone production, suggesting that endogenous IGF-I is functionally involved in GH effects on progesterone induction. BMP inhibited IGF-I effects that increased FSH-induced estradiol production with suppression of expression of the GH/IGF-I system, whereas GH/IGF-I actions impaired BMP-Sma and Mad related protein 1/5/8 signaling through down-regulation of the expression of BMP receptors. Thus, GH acts to modulate estrogen and progesterone production differentially through endogenous IGF-I activity in granulosa cells, in which GH IGF-I interaction leads to antagonization of BMP actions including suppression of FSH-induced progesterone production. Mutual balance between GH/IGF-I and BMP signal intensities may be a key for regulating gonadotropin-induced steroidogenesis in growing follicles. PMID- 22067324 TI - Constitutive activation of IKKbeta in adipose tissue prevents diet-induced obesity in mice. AB - The IkappaB kinase beta (IKKbeta) is a master kinase involved in obesity-related inflammation and insulin resistance through nuclear factor kappaB dependent and independent pathways. However, the effect of IKKbeta activation in adipose tissue, the organ critical for storage of excessive energy and initiation of inflammatory responses in the context of obesity, on systemic insulin sensitivity and metabolism, has not been investigated. In our study, we found that mice overexpressing the constitutively active IKKbeta in adipose tissue under the control of murine adipocyte fatty acid binding protein (aP2) promoter were protected from age-related and diet-induced body weight gains, despite increased food intake. The aP2-IKKbeta SE mice have significantly reduced weights in all white adipose tissue depots and reduced triglyceride contents in adipose tissue, liver, and muscle. Despite increased systemic and tissue inflammation, aP2 IKKbeta SE mice displayed decreased blood glucose levels, improved glucose, and insulin tolerance. This may be at least partially attributable to increased energy expenditure. Histological analysis revealed presence of many small adipocytes in white adipose tissue of aP2-IKKbeta SE mice fed on high-fat diet. Furthermore, transgenic expression of IKKbeta in adipose tissue improved high-fat diet-induced hepatosteatosis. Collectively, increased energy expenditure and reduced plasma free fatty acid levels may contribute to enhanced systemic insulin sensitivity in aP2-IKKbeta SE mice. Our study demonstrates that presence of inflammation in adipose tissue before the development of obesity has beneficial effect on metabolism. PMID- 22067325 TI - Forkhead box A1 (FOXA1) and A2 (FOXA2) oppositely regulate human type 1 iodothyronine deiodinase gene in liver. AB - Type 1 iodothyronine deiodinase (D1), a selenoenzyme that catalyzes the bioactivation of thyroid hormone, is expressed mainly in the liver. Its expression and activity are modulated by several factors, but the precise mechanism of its transcriptional regulation remains unclear. In the present study, we have analyzed the promoter of human D1 gene (hDIO1) to identify factors that prevalently increase D1 activity in the human liver. Deletion and mutation analyses demonstrated that a forkhead box (FOX)A binding site and an E-box site within the region between nucleotides -187 and -132 are important for hDIO1 promoter activity in the liver. EMSA demonstrated that FOXA1 and FOXA2 specifically bind to the FOXA binding site and that upstream stimulatory factor (USF) specifically binds to the E-box element. Overexpression of FOXA2 decreased hDIO1 promoter activity, and short interfering RNA-mediated knockdown of FOXA2 increased the expression of hDIO1 mRNA. In contrast, overexpression of USF1/2 increased hDIO1 promoter activity. Short interfering RNA-mediated knockdown of FOXA1 decreased the expression of hDIO1 mRNA, but knockdown of both FOXA1 and FOXA2 restored it. The response of the hDIO1 promoter to USF was greatly attenuated in the absence of FOXA1. Taken together, these results indicate that a balance of FOXA1 and FOXA2 expression modulates hDIO1 expression in the liver. PMID- 22067326 TI - betaC1 of chili leaf curl betasatellite is a pathogenicity determinant. AB - BACKGROUND: Cotton leaf curl disease in the Indian subcontinent is associated with several distinct begomoviruses that interact with a disease-specific DNA satellite named Cotton leaf curl Multan betasatellite (CLCuMB). However, we have recently reported that Chili leaf curl betasatellite (ChLCB) is also occasionally found associated with the disease in Pakistan. The question as to whether ChLCB contributes to the development of disease symptoms such as leaf curling and enations remain to be answered. We have previously shown that the expression of betaC1 of CLCuMB develops all symptoms of cotton leaf curl disease in Nicotiana benthamiana when expressed from PVX vector. FINDINGS: The role of ChLCB in the induction of typical disease symptoms was studied by its expression from PVX vector in N. benthamiana. The expression of betaC1 from PVX vector developed severe leaf curl symptoms and leaf-like enations that resemble the phenotype induced by betaC1 of CLCuMB. CONCLUSIONS: The results presented here show that the expression of betaC1 of ChLCB from PVX vector exhibit phenotype typical of cotton leaf curl and therefore ChLCB may contribute to the disease symptoms. PMID- 22067328 TI - Dissociation and emotion regulation in borderline personality disorder. AB - BACKGROUND: Although some evidence suggests that borderline personality disorder (BPD) is primarily a disorder of the emotion regulation system, findings remain inconsistent. One potential explanation for this is the moderating role of dissociation. METHOD: In this study, 33 female subjects with BPD and 26 healthy controls (HC; matched by education level and nicotine intake) were presented idiographic aversive, standard unpleasant and neutral scripts. Modulation of startle reflex and electrodermal responses (skin conductance level; SCL) were measured during imagery of emotional and neutral scripts. Additionally, self reports of emotional experience (valence and arousal) and present-state dissociation were assessed. RESULTS: Patients with BPD showed elevated levels of dissociative experiences during testing. Present-state dissociation mediated group differences in SCL and startle response between the HC and BPD groups. CONCLUSIONS: These results suggest that careful attention must be paid to the moderating effect of dissociative symptoms on the psychophysiological responses of BPD patients. Furthermore, the findings have important implications for the assessment and treatment of BPD, including the need to carefully assess BPD patients for dissociative symptoms and to incorporate the treatment of dissociation. PMID- 22067327 TI - Exploring the gonad transcriptome of two extreme male pigs with RNA-seq. AB - BACKGROUND: Although RNA-seq greatly advances our understanding of complex transcriptome landscapes, such as those found in mammals, complete RNA-seq studies in livestock and in particular in the pig are still lacking. Here, we used high-throughput RNA sequencing to gain insight into the characterization of the poly-A RNA fraction expressed in pig male gonads. An expression analysis comparing different mapping approaches and detection of allele specific expression is also discussed in this study. RESULTS: By sequencing testicle mRNA of two phenotypically extreme pigs, one Iberian and one Large White, we identified hundreds of unannotated protein-coding genes (PcGs) in intergenic regions, some of them presenting orthology with closely related species. Interestingly, we also detected 2047 putative long non-coding RNA (lncRNA), including 469 with human homologues. Two methods, DEGseq and Cufflinks, were used for analyzing expression. DEGseq identified 15% less expressed genes than Cufflinks, because DEGseq utilizes only unambiguously mapped reads. Moreover, a large fraction of the transcriptome is made up of transposable elements (14500 elements encountered), as has been reported in previous studies. Gene expression results between microarray and RNA-seq technologies were relatively well correlated (r = 0.71 across individuals). Differentially expressed genes between Large White and Iberian showed a significant overrepresentation of gamete production and lipid metabolism gene ontology categories. Finally, allelic imbalance was detected in ~ 4% of heterozygous sites. CONCLUSIONS: RNA-seq is a powerful tool to gain insight into complex transcriptomes. In addition to uncovering many unnanotated genes, our study allowed us to determine that a considerable fraction is made up of long non-coding transcripts and transposable elements. Their biological roles remain to be determined in future studies. In terms of differences in expression between Large White and Iberian pigs, these were largest for genes involved in spermatogenesis and lipid metabolism, which is consistent with phenotypic extreme differences in prolificacy and fat deposition between these two breeds. PMID- 22067329 TI - KBA62 and PNL2: 2 new melanoma markers-immunohistochemical analysis of 1563 tumors including metastatic, desmoplastic, and mucosal melanomas and their mimics. AB - Identification of metastatic melanoma can be difficult because of its considerable morphologic variation and mimicry of a wide variety of other tumors. The more melanoma-specific melanoma markers, MelanA/MART-1, HMB45, and tyrosinase, used in addition to S100 protein, all have limitations in sensitivity and specificity. In this study, we evaluated 2 new melanoma markers, monoclonal antibodies KBA62 and PNL2 to yet unidentified antigens, using a large panel of metastatic melanomas (n=214), desmoplastic melanomas (n=34), gastrointestinal mucosal melanomas (n=54), benign nevi (n=27), clear cell sarcomas (n=16), and nonmelanocytic tumors (n=1218). Immunoreactivity for KBA62 and PNL2 was found in all pigmented nevi and in 86% and 90% of metastatic melanomas, respectively. Mucosal melanomas showed a similar rate of PNL2 immunoreactivity but somewhat less frequent KBA62 positivity (72%). In addition, KBA62 was found to be a sensitive diagnostic marker for desmoplastic melanoma (28 of 34; 82%), whereas PNL2 was only rarely positive (2 of 34; 6%). KBA62-positive normal tissues included pericytes, vascular and parenchymal smooth muscles, and basal cells of complex epithelia, including myoepithelia, whereas PNL2 labeled only melanocytes and neutrophils. Among nonmelanocytic tumors, those that were KBA62 positive were nodular fasciitis, leiomyoma and leiomyosarcoma, gastrointestinal stromal tumors, benign and malignant nerve sheath tumors, synovial sarcoma, and subsets of various carcinomas, especially those with squamous cell/stratified epithelial differentiation. PNL2 positivity in nonmelanocytic tumors was more restricted but occurred consistently in angiomyolipoma and other perivascular epitheloid cell tumor and in chronic myeloid leukemia tissue infiltrates. KBA62 may assist in the identification of desmoplastic melanomas, but its widespread occurrence in nonmelanomas limits utility. PNL2 is highly specific for melanomas but lacks reactivity with desmoplastic melanomas. It is also an excellent supplementary marker for perivascular epitheloid cell tumor at various sites. PMID- 22067330 TI - Absence of Merkel cell polyomavirus in primary parotid high-grade neuroendocrine carcinomas regardless of cytokeratin 20 immunophenotype. AB - High-grade neuroendocrine carcinoma of the salivary glands is a rare malignancy that can be difficult to distinguish from metastatic neuroendocrine (Merkel cell) carcinoma of the skin, which often occurs on the head and neck and may metastasize to lymph nodes in or adjacent to salivary glands, particularly the parotid gland. As the 2 tumors have morphologic and immunophenotypic overlap, additional diagnostic tools may be clinically useful. Merkel cell carcinoma is known to harbor Merkel cell polyomavirus in up to 80% of cases. However, the presence or absence of this virus in salivary gland neuroendocrine carcinomas has not been investigated. We evaluated 7 primary salivary gland high-grade neuroendocrine carcinomas (all from the parotid) for the virus by both immunohistochemistry (CM2B4 clone) and real-time polymerase chain reaction directed against the conserved small T antigen. Five of the tumors had small cell morphology, and 2 had large cell morphology. All were either chromogranin and/or synaptophysin positive. Four of the 5 small cell (80%) and 1 of the 2 large cell (50%) carcinomas were cytokeratin 20 positive. All but 1 case had cervical lymph node metastases at presentation. Merkel cell polyomavirus T antigen was not detected in any of the 7 tumors, either by immunohistochemistry or by polymerase chain reaction with adequate controls. These observations suggest that primary parotid high-grade neuroendocrine carcinoma arises from a biological pathway that is different from that of cutaneous Merkel cell carcinomas. Furthermore, viral testing may aid in distinguishing the 2 tumor types, as a positive result would favor a metastasis. PMID- 22067331 TI - Prox1 transcription factor as a marker for vascular tumors-evaluation of 314 vascular endothelial and 1086 nonvascular tumors. AB - Prox1, a transcription factor important in the regulation and maintenance of the lymphatic endothelial phenotype, is consistently expressed in lymphangiomas and Kaposi sarcoma and has also been reported in Kaposiform hemangioendothelioma. However, information on its distribution in vascular tumors, such as angiosarcoma, is limited. In this study, we examined selected normal tissues and 314 vascular endothelial and 1086 nonvascular tumors to get an insight into the biology of these tumors and on potential diagnostic use of Prox1 as an immunohistochemical marker. In adult tissues, Prox1 was essentially restricted to lymphatic endothelia, with expression in subsets of pancreatic and gastrointestinal epithelia. However, it was also detected in embryonic liver and heart. Prox1 was consistently expressed in lymphangiomas, venous hemangiomas, Kaposi sarcoma, in endothelia of spindle cell hemangioma, Kaposiform hemangioendothelioma, and retiform hemangioendothelioma, and in half of epithelioid hemangioendotheliomas. It was present in most cutaneous angiosarcomas from different sites but was less commonly expressed in deep soft tissue and visceral angiosarcomas. In contrast, Prox1 was generally absent in capillary and cavernous hemangiomas. In positive hemangiomas and angiosarcomas it was coexpressed with podoplanin, another marker of the lymphatic endothelial phenotype. There was an inverse correlation with CD34 expression. The expression in mesenchymal nonendothelial neoplasm was limited. Prox1 was detected in 5 of 27 synovial sarcomas, specifically in the epithelia of biphasic tumors. Four of 16 Ewing sarcomas and 5 of 15 paragangliomas were also positive. All melanomas and undifferentiated sarcomas were negative. Among epithelial neoplasms, Prox1 was detected in 18 of 38 colonic carcinomas and 10 of 15 cholangiocarcinomas and in a minority of pulmonary, prostatic, and endometrial adenocarcinomas. The common Prox1 expression in angiosarcoma and its rare presence in nonvascular mesenchymal tumors make this marker suitable for the diagnosis of angiosarcoma and Kaposi sarcoma. However, the presence of Prox1 in some malignant epithelial tumors necessitates caution in applying Prox1 as a marker for vascular tumors. Common Prox1 expression in angiosarcoma may reflect the lymphatic endothelial phenotype in these tumors. Its patterns of expression in hemangiomas and angiosarcoma may be diagnostically useful and offer a new parameter in the biological classification of vascular tumors. PMID- 22067332 TI - Pax8 detection in well-differentiated pancreatic endocrine tumors: how reliable is it? PMID- 22067333 TI - Prediction of adenocarcinoma in esophagectomy specimens based upon analysis of preresection biopsies of Barrett esophagus with at least high-grade dysplasia: a comparison of 2 systems. AB - Distinguishing Barrett esophagus with high-grade dysplasia (BE-HGD) from intramucosal and submucosal adenocarcinomas on biopsies is challenging, yet important, in the choice of therapy. The current study evaluates preresection biopsies from patients who underwent esophagectomy for at least BE-HGD, to compare the recently published histologic categories by the University of Michigan (UM) and Cleveland Clinic (CC), correlate preresection and final resection diagnosis, and identify histologic features in biopsies that might be predictive of adenocarcinoma on esophagectomy. A total of 112 cases with a consensus biopsy diagnosis (agreement by >=4 of 7 gastrointestinal pathologists) were statistically analyzed to identify histologic features that predicted adenocarcinoma on resection. Applying the UM criteria to the biopsy series showed excellent agreement with the CC system (kappa=0.86) and significant correlation between preoperative and esophagectomy diagnoses (P<0.001). The likelihood of finding carcinoma on resection was significantly higher with the category of HGD with marked glandular distortion cannot exclude intramucosal adenocarcinoma [CC; odd ratio (OR), 2.8; P=0.046] or HGD suspicious for adenocarcinoma (UM; OR, 4.3; P=0.008), compared to HGD alone. The presence of "never-ending" glands (OR, 3.7; P=0.008), sheet-like growth (P<0.001), angulated glands (OR, 8.5; P<0.001), >=3 dilated glands with intraluminal debris (OR, 2.6; P=0.05), and >1 focus of single cell infiltration into the lamina propria (OR, 8.9; P<0.001) increased the odds of finding carcinoma on resection. The latter 2 variables remained independent predictors of adenocarcinoma in multivariable analysis. In conclusion, the CC and UM systems show excellent agreement and define histologic categories that can improve prediction of adenocarcinoma on resection. PMID- 22067334 TI - "Null pattern" of immunoreactivity in a Lynch syndrome-associated colon cancer due to germline MSH2 mutation and somatic MLH1 hypermethylation. AB - Lynch syndrome accounts for approximately 3% of newly diagnosed colorectal cancers and is caused by germline defects in DNA mismatch repair genes. Screening of patients for Lynch syndrome can be done by immunohistochemical staining for a panel of mismatch repair proteins and/or DNA testing for microsatellite instability. We describe a unique "null" immunophenotype in a Lynch syndrome associated colon cancer in a 71-year-old woman who also had a personal history of ureteral cancer and a strong family history of various malignancies. Immunohistochemical stains for MLH1, MSH2, PMS2, and MSH6 were completely negative in the tumor cells, with positive staining in stromal and inflammatory cells. Mutation analysis using peripheral blood showed a germline G587R mutation in the MSH2 gene. Further testing revealed the tumor to be positive for MLH1 promoter hypermethylation. Normal colonic mucosa adjacent to the tumor was negative for MLH1 promoter methylation. The lack of immunostaining for any of the 4 DNA mismatch repair proteins in this extremely unusual case was, therefore, related to a germline MSH2 mutation and somatic MLH1 promoter hypermethylation. PMID- 22067335 TI - Video as poetry: Felix in Exile (1994) by William Kentridge (b. 1955). PMID- 22067336 TI - Electrostimulation mapping of spatial neglect. AB - BACKGROUND: Cortical and subcortical electrostimulation mapping during awake brain surgery for tumor removal is usually used to minimize deficits. OBJECTIVE: To use electrostimulation to study neuronal substrates involved in spatial awareness in humans. METHODS: Spatial neglect was studied using a line bisection task in combination with electrostimulation mapping of the right hemisphere in 50 cases. Stimulation sites were identified with Talairach coordinates. The behavioral effects induced by stimulation, especially eye movements and deviations from the median, were quantified and compared with preoperative data and a control group. RESULTS: Composite and highly individualized spatial neglect maps were generated. Both rightward and leftward deviations were induced, sometimes in the same patient but for different stimulation sites. Group analysis showed that specific and reproducible line deviations were induced by stimulation of discrete cortical areas located in the posterior part of the right superior and middle temporal gyri, inferior parietal lobe, and inferior postcentral and inferior frontal gyri (P < .05). Fiber tracking identified stimulated subcortical areas important to spare as sections of fronto-occipital and superior longitudinal II fascicles. According to preoperative and postoperative neglect battery tests, the specificity and sensitivity of intraoperative line bisection tests were 94% and 83%, respectively. CONCLUSION: In humans, discrete cortical areas that are variable in location between individuals but mainly located within the right posterior Sylvian fissure sustain visuospatial attention specifically toward the contralateral or ipsilateral space direction. Line bisection mapping was found to be a reliable method for minimizing spatial neglect caused by brain tumor surgery. PMID- 22067340 TI - A better understanding of myelination using nano-indentation. PMID- 22067341 TI - Predicting the first site of relapse for cancerous tumors using protein expression profiles. PMID- 22067342 TI - Seizures and free radicals: the antioxidant may become the next anticonvulsant. PMID- 22067343 TI - The effect of endothelin receptor antagonists on vasospasm following aneurysmal subarachnoid hemorrhage. PMID- 22067344 TI - Enhancing memory via stimulation: a promising new technique? PMID- 22067345 TI - SAMMPRIS: end of intracranial stenting for atherosclerosis or back to the drawing board? PMID- 22067346 TI - Direct conversion of human fibroblasts to functional neurons in one step. PMID- 22067347 TI - Neurosurgery tops malpractice risk. PMID- 22067359 TI - Hypertriglyceridemic pancreatitis in infant with erysipelas. PMID- 22067362 TI - Protein acetylation and aging. AB - Our results suggest the possible benefit of manipulating an intrinsic aging pathway that is independent of nutrition availability, a potential therapeutic route that might be able to bypass shortcomings of calorie restriction. PMID- 22067349 TI - Three interrelated themes in current breast cancer research: gene addiction, phenotypic plasticity, and cancer stem cells. AB - Recent efforts to understand breast cancer biology involve three interrelated themes that are founded on a combination of clinical and experimental observations. The central concept is gene addiction. The clinical dilemma is the escape from gene addiction, which is mediated, in part, by phenotypic plasticity as exemplified by epithelial-to-mesenchymal transition and mesenchymal-to epithelial transition. Finally, cancer stem cells are now recognized as the basis for minimal residual disease and malignant progression over time. These themes cooperate in breast cancer, as induction of epithelial-to-mesenchymal transition enhances self-renewal and expression of cancer stem cells, which are believed to facilitate tumor resistance. PMID- 22067363 TI - Spatial and temporal distribution patterns of enkephalinergic neurons in adult and developing retinas of the preproenkephalin-green fluorescent protein transgenic mouse. AB - Enkephalin (ENK) peptides are present in the retina of several vertebrate species and play a crucial role in establishing specific circuits during retinal development. However, there is no information available concerning the development of ENKergic neurons in the mouse retina. To address this question, we used preproenkephalin-enhanced green fluorescent protein (GFP) transgenic mice, in which ENKergic neurons are revealed by GFP. Our results showed that most GFP positive cells were located in the proximal part of the inner nuclear layer with a scattering of GFP-immunoreactive cells in the ganglion cell layer (GCL) in the adult retina. Double immunostaining with syntaxin indicates that GFP expression was restricted to a population of amacrine cells. The proportions of glycine transporter-1 and gamma-aminobutyric acid-positive cells among ENKergic neurons were 57.3 +/- 2.4% and 10.1 +/- 1.8%, respectively. We then injected retrograde tracer into the superior colliculus and observed that none of the ENKergic neurons in the GCL were retrogradely labeled with the tracer. GFP-positive cells were first observed at embryonic day (E) 15 in the inner neuroblastic layer at only very low levels, which gradually increased until E18. After birth, there was a steep rise in GFP expression levels, reaching maximal activity by postnatal day (P) 7. The distribution and intensity of GFP-positive cells at P15 were similar to those of adult retina. It was found that immunoreactive processes in the inner plexiform layer formed strongly stained patches. The present results provide detailed morphological evidence of the cell type and spatial and temporal distribution of ENKergic neurons in the retina. PMID- 22067364 TI - Particle filter with a mode tracker for visual tracking across illumination changes. AB - In this correspondence, our goal is to develop a visual tracking algorithm that is able to track moving objects in the presence of illumination variations in the scene and that is robust to occlusions. We treat the illumination and motion ( x y translation and scale) parameters as the unknown "state" sequence. The observation is the entire image, and the observation model allows for occasional occlusions (modeled as outliers). The nonlinearity and multimodality of the observation model necessitate the use of a particle filter (PF). Due to the inclusion of illumination parameters, the state dimension increases, thus making regular PFs impractically expensive. We show that the recently proposed approach using a PF with a mode tracker can be used here since, even in most occlusion cases, the posterior of illumination conditioned on motion and the previous state is unimodal and quite narrow. The key idea is to importance sample on the motion states while approximating importance sampling by posterior mode tracking for estimating illumination. Experiments demonstrate the advantage of the proposed algorithm over existing PF-based approaches for various face and vehicle tracking. We are also able to detect illumination model changes, e.g., those due to transition from shadow to sunlight or vice versa by using the generalized expected log-likelihood statistics and successfully compensate for it without ever loosing track. PMID- 22067365 TI - Commutability of blur and affine warping in super-resolution with application to joint estimation of triple-coupled variables. AB - This paper proposes a new approach to the image blind super-resolution (BSR) problem in the case of affine interframe motion. Although the tasks of image registration, blur identification, and high-resolution (HR) image reconstruction are coupled in the imaging process, when dealing with nonisometric interframe motion or without the exact knowledge of the blurring process, classic SR techniques generally have to tackle them (maybe in some combinations) separately. The main difficulty is that state-of-the-art deconvolution methods cannot be straightforwardly generalized to cope with the space-variant motion. We prove that the operators of affine warping and blur commute with some additional transforms and derive an equivalent form of the BSR observation model. Using this equivalent form, we develop an iterative algorithm to jointly estimate the triple coupled variables, i.e., the motion parameters, blur kernels, and HR image. Experiments on synthetic and real-life images illustrate the performance of the proposed technique in modeling the space-variant degradation process and restoring local textures. PMID- 22067366 TI - Incentives in the family II: behavioral dynamics and the evolution of non-costly signaling. AB - In many biological and social interactions, individuals with private information have incentives to misrepresent their information. A prominent example is when offspring know their need or condition but the parents do not. Theory showed that signal costs can ensure truthful communication in such situations, but further studies have cast in doubt whether empirically measured costs are high enough to sustain honesty, and whether the costly signaling equilibrium represents a fitness advantage over non-signaling. Here, I tackle these issues with a model of signaling that takes place at the behavioral time-scale through dynamic responses of individuals to each other. I then embed this behavioral model in an evolutionary one that asks how the decision rules of the parent and offspring evolve in response to the trade-off between signal costs and the costs of provisioning. I find that a non-costly honest signaling equilibrium can evolve when relatedness between siblings is above a certain threshold. This threshold is lower when (i) offspring get satiated more quickly, (ii) the cost of provisioning to the parent escalates less rapidly, or (iii) the variation in offspring need is higher. These results provide a potential resolution to the apparent paradox of costly begging. I also discuss the relation between costly signaling and mechanism design theories. PMID- 22067367 TI - Preventive and minimal intervention dentistry in the undergraduate curriculum. AB - OBJECTIVES: This paper illustrates the preventive and minimal intervention dentistry (MI) concepts with examples from cariology, but the philosophy is much wider and should have an impact across all dental specialties and the entire undergraduate curriculum. Collaboration between researchers, educators and clinical dentists is very important for the continuing improvement of dentistry. METHODS: This paper considers the potential of preventive dentistry and "MI Dentistry" and then outlines a modern core cariology curriculum recently developed for use across Europe. Related initiatives from the ICDAS Foundation's ICCMSTM (International Caries Classification and Management System), the International Association for Dental Research and the Alliance for a Cavity Free Future (ACFF) are also outlined. CONCLUSIONS: Preventive and minimal intervention dentistry are important topics, both for the present and increasingly for the future. PMID- 22067368 TI - Estrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study report. AB - BACKGROUND: It remains unclear whether estrogenic botanical supplement (EBS) use influences breast cancer survivors' health-related outcomes. METHODS: We examined the associations of EBS use with health-related quality of life (HRQOL), with fatigue, and with 15 hormone-related symptoms such as hot flashes and night sweats among 767 breast cancer survivors participating in the Health, Eating, Activity, and Lifestyle (HEAL) Study. HRQOL was measured by the Medical Outcomes Study short form-36 physical and mental component scale summary score. Fatigue was measured by the Revised-Piper Fatigue Scale score. RESULTS: Neither overall EBS use nor the number of EBS types used was associated with HRQOL, fatigue, or hormone-related symptoms. However, comparisons of those using each specific type of EBS with non-EBS users revealed the following associations. Soy supplements users were more likely to have a better physical health summary score (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.02-2.70). Flaxseed oil users were more likely to have a better mental health summary score (OR = 1.76, 95% CI = 1.05-2.94). Ginseng users were more likely to report severe fatigue and several hormone-related symptoms (all ORs >= 1.7 and all 95% CIs exclude 1). Red clover users were less likely to report weight gain, night sweats, and difficulty concentrating (all OR approximately 0.4 and all 95% CIs exclude 1). Alfalfa users were less likely to experience sleep interruption (OR = 0.28, 95% CI = 0.12 0.68). Dehydroepiandrosterone users were less likely to have hot flashes (OR = 0.33, 95% CI = 0.14-0.82). CONCLUSIONS: Our findings indicate that several specific types of EBS might have important influences on a woman's various aspects of quality of life, but further verification is necessary. PMID- 22067369 TI - Application of multiplex PCR approaches for shark molecular identification: feasibility and applications for fisheries management and conservation in the Eastern Tropical Pacific. AB - Here we describe the application of new and existing multiplex PCR methodologies for shark species molecular identification. Four multiplex systems (group ID, thresher sharks, hammerhead sharks and miscellaneous shark) were employed with primers previously described and some designed in this study, which allow for species identification after running PCR products through an agarose gel. This system was implemented for samples (bodies and fins) collected from unidentified sharks landed in the port of Buenaventura and from confiscated tissues obtained from illegal fishing around the Malpelo Island Marine Protected Area, Pacific Coast of Colombia. This method has allowed reliable identification, to date, of 407 samples to the genus and/or species levels, most of them (380) identified as the pelagic thresher shark (Alopias pelagicus). Another seven samples were identified as scalloped hammerhead sharks (Sphyrna lewini). This is an easy-to implement and reliable identification method that could even be used locally to monitor shark captures in the main fishing ports of developed and developing countries. PMID- 22067370 TI - Serum superoxide dismutase and malondialdehyde levels in a group of Chinese patients with age-related macular degeneration. AB - BACKGROUND AND AIMS: The aim of this study was to investigate superoxide dismutase (SOD) activity together with malondialdehyde (MDA) levels in a group of Chinese patients with age-related macular degeneration (AMD). METHODS: Serum SOD activity and MDA levels were analysed in 56 AMD patients with subtypes (early dry, geographic atrophy, and wet) and 34 healthy controls matched with age and sex. RESULTS: Serum MDA levels were significantly higher in AMD (3.68 +/- 1.06 nmol/mL) than in controls (2.83 +/- 0.43 nmol/mL; p=0.000), and was significantly higher in wet AMD (3.79 +/- 0.79 nmol/mL) than in early dry AMD (3.26 +/- 0.99 nmol/mL; p=0.038). Serum SOD activity was significantly higher in AMD (87.12 +/- 13.22 U/mL) than in controls (79.91 +/- 11.80 U/mL; p=0.012), and slightly higher in wet AMD (89.52 +/- 16.25 U/mL) than in GA (83.62 +/- 9.75 U/mL; p=0.275) and early dry AMD (81.64 +/- 18.90 U/mL; p=0.093). There was a positive correlation between serum MDA levels and SOD activities in AMD patients and controls (r=0.320, p=0.002). CONCLUSIONS: The observed increase in SOD activity in our study may be related to increased MDA levels, as a compensatory regulation in response to oxidative stress in AMD patients. The present data also demonstrate that oxido-reduction disturbance may be hypothesized in the pathogenesis of AMD. PMID- 22067371 TI - Differences according to gender and health status in CD4:CD8 ratio in a sample of community-dwelling oldest old. The OCTABAIX immune study. AB - BACKGROUND AND AIMS: The presence of an immune-risk phenotype (IRP) has been correlated with survival rates in elderly people. The aim of this study is to characterize the inverted CD4:CD8 ratio as a possible marker of IRP in a sample of oldest old (85 years) by assessing differences in gender and health status. METHODS: Comorbidity, functional status (Barthel Index), and cognitive status with the Spanish version of the Mini-Mental State Examination were evaluated. Non disabled subjects were defined as those with better health status, with scores of >90 on the Barthel Index and >23 points on the Spanish version of the Mini-Mental State Examination. CD4:CD8 ratios were recorded, and a ratio of 1.00 or less was used to define IRF. RESULTS: Three hundred and twelve subjects aged 85 years old were studied, 190 women (60.9%) and 122 men. The CD4:CD8 ratio was 1.00 or less in 47 subjects (15.6%) and higher than 2.2 in 115 (36.8%). There were no differences in CD4:CD8 ratio according to health status. The inverted CD4:CD8 ratio was more frequent in men (55.3%). CONCLUSION: In this community-dwelling, single year birth cohort study, the subgroup with poor health status did not have a lower CD4:CD8 ratio. The inverted CD4:CD8 ratio was more frequent in men. PMID- 22067372 TI - Association between generic and disease-specific quality of life questionnaires and mobility and balance among women with osteoporosis and vertebral fractures. AB - BACKGROUND AND AIMS: The aims of this study were to assess correlations between two health-related quality of life (HRQOL) measurements, the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis (QUALEFFO- 41) and the total score of The General Health Questionnaire (GHQ-20) in a population of women living at home with well-established osteoporosis and at least one vertebral fracture, as well as the internal consistency and floor and ceiling effects of these measurements. Also examined were the mean values of these measurements, to ascertain whether they were significantly different for the group consisting of 75% of the women with the best performance on mobility and balance, compared with the other participants. METHODS: Across-sectional study of 89 women aged 60 years or more, evaluated by QUALEFFO-41 (consisting of one total score and five section scores), GHQ-20 (one total score), maximum speed and Functional Reach (FR). RESULTS: Cronbach's alpha coefficient for measurements of HRQOL ranged from 0.61 to 0.92. Significant correlations between 'QUALEFFO- 41: total score' and 'GHQ-20: total score' were 0.49, and between 'GHQ-20: total score' and section scores of 'QUALEFFO-41' 0.28-0.63. Those in the 75% group with the highest maximum walking speed or longest distance on FR reported significantly better disease-specific HRQOL than the others, with poorer results on these tests. CONCLUSIONS: Disease-specific and generic HRQOL instruments are not redundant when applied together, and the disease-specific 'QUALEFFO-41' and generic GHQ-20 measure different aspects of HRQOL. PMID- 22067373 TI - Carotid sinus syndrome is common in very elderly patients undergoing tilt table testing and carotid sinus massage because of syncope or unexplained falls. AB - BACKGROUND AND AIMS: Although the incidence of falls and syncope increase with age, the underlying mechanisms are not fully understood, particularly in very old patients. We report diagnostic outcomes of tilt table and carotid sinus massage (TT/CSM) testing in a population of older old subjects (82% over 80 years of age) referred for TT/CSM from a falls clinic for assessment of syncope or unexplained falls. METHODS: Prospective observational study between January 1, 2001 and January 1, 2005 involving 290 consecutive subjects undergoing TT/CSM testing according to European Society of Cardiology guidelines for the diagnosis and management of syncope. RESULTS: Combination of TT/CSM provided a positive result in 62% of subjects, and was significantly more likely to be positive in subjects over the age of 80 (68% vs 50%, p=0.001). Carotid sinus syndrome (CSS) was the most common diagnosis, and was significantly more common in subjects over 80 (48% vs 34%, p=0.022) particularly due to a higher incidence of mixed CSS (16% vs 7%, p=0.023). There was no significant difference in the diagnosis of subjects referred due to falls and those reporting syncope (p=0.93). No cardiovascular or neurological adverse events occurred. CONCLUSIONS: In our cohort of very elderly patients, the diagnostic accuracy of tilt testing and carotid sinus massage was high and adverse incidents absent when testing was indicated by a geriatrician experienced in the assessment of falls and syncope. We advocate the use of TT/CSM testing as part of a comprehensive falls/syncope assessment for the diagnostic evaluation of older patients presenting with unexplained falls and/or syncope in whom structured assessment has not identified a cause for their symptoms. PMID- 22067374 TI - Examination of the relationship between age and clinical function: missing the trees for the wood. PMID- 22067375 TI - Surfactant lavage therapy for meconium aspiration syndrome: a systematic review and meta-analysis. AB - BACKGROUND: Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully established. OBJECTIVE: To investigate the effects of surfactant lavage therapy for MAS by a systematic meta-analysis. METHODS: Relevant studies were identified by database searches in MEDLINE (from 1950), EMBASE (from 1980), and CENTRAL, up to June 2010, and by additional hand searches. Meta-analyses were separately conducted for randomized controlled trials (RCTs) and non-randomized controlled studies (NRSs). Risk of bias was assessed and clinical as well as statistical heterogeneities were also investigated in explaining the potential bias. RESULTS: Two RCTs (87 patients) and eight NRSs (178 patients) were identified. From the results of the meta analysis of RCTs, surfactant lavage significantly decreased death or the need for extracorporeal membrane oxygenation (RR 0.34, 95% CI 0.11, 0.99). An interventional benefit was indicated for other outcomes, although it was not statistically significant based only on the two RCTs. Results from the analysis of outcomes from NRSs are consistent with those from RCTs and demonstrated a beneficial effect, which could be considered as supporting evidence. CONCLUSIONS: Lung lavage with diluted surfactant appeared to improve the clinical outcome in infants with MAS. Given that less than 100 infants were included in the two RCTs, the findings of this study may still be regarded as insufficient evidence. Further research will be needed to confirm the benefit as well as to refine the lavage technique. PMID- 22067383 TI - IL-15 administered by continuous infusion to rhesus macaques induces massive expansion of CD8+ T effector memory population in peripheral blood. AB - IL-15 promotes activation and maintenance of natural killer (NK) and CD8(+) T effector memory (T(EM)) cells, making it a potential immunotherapeutic agent for the treatment of cancer and immunodeficiency states. Here we report the immunologic effects of 3 different IL-15 dosing strategies in Rhesus macaques. IL 15 at a dose of 20 MUg/kg/d administered by continuous intravenous infusion for 10 days resulted in a massive (100-fold) expansion of CD8(+) T(EM) cells in the peripheral blood. In contrast, the administration of 20-40 MUg/kg/d of IL-15 by subcutaneous injection resulted in a more modest (10-fold) expansion of CD8(+) T(EM) cells. NK expansion was similar in both the continuous intravenous and daily subcutaneous treatment groups. The observation that IL-15 administered by continuous intravenous infusion is able to induce markedly greater expansions of CD8(+) T(EM) cells than the same dose administered by other routes may have important implications for clinical development of this cytokine. PMID- 22067384 TI - Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia. AB - Antithymocyte globulin (ATG) + cyclosporine is effective in restoring hematopoiesis in severe aplastic anemia (SAA). We hypothesized that the humanized anti-CD52 mAb alemtuzumab might be active in SAA because of its lymphocytotoxic properties. We investigated alemtuzumab monotherapy from 2003-2010 in treatment naive, relapsed, and refractory SAA in 3 separate research protocols at the National Institutes of Health. Primary outcome was hematologic response at 6 months. For refractory disease, patients were randomized between rabbit ATG + cyclosporine (n = 27) and alemtuzumab (n = 27); the response rate for alemtuzumab was 37% (95% confidence interval [CI], 18%-57%) and for rabbit ATG 33% (95% CI, 14%-52%; P = .78). The 3-year survival was 83% (95% CI, 68%-99%) for alemtuzumab and 60% (95% CI, 43%-85%) for rabbit ATG (P = .16). For relapsed disease (n = 25), alemtuzumab was administered in a single-arm study; the response rate was 56% (95% CI, 35%-77%) and the 3-year survival was 86% (95% CI, 72%-100%). In treatment-naive patients (n = 16), alemtuzumab was compared with horse and rabbit ATG in a 3-arm randomized study; the response rate was 19% (95% CI 0%-40%), and the alemtuzumab arm was discontinued early. We conclude that alemtuzumab is effective in SAA, but best results are obtained in the relapsed and refractory settings. The present trials were registered at www.clinicaltrials.gov as NCT00195624, NCT00260689, and NCT00065260. PMID- 22067385 TI - Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology. AB - In response to microenvironmental signals, macrophages undergo different activation, including the "classic" proinflammatory phenotype (also called M1), the "alternative" activation induced by the IL-4/IL-13 trigger, and the related but distinct heterogeneous M2 polarization associated with the anti-inflammatory profile. The latter is induced by several stimuli, including IL-10 and TGF-beta. Macrophage-polarized activation has profound effects on immune and inflammatory responses and in tumor biology, but information on the underlying molecular pathways is scarce. In the present study, we report that alternative polarization of macrophages requires the transcription factor c-MYC. In macrophages, IL-4 and different stimuli sustaining M2-like polarization induce c-MYC expression and its translocation to the nucleus. c-MYC controls the induction of a subset (45%) of genes associated with alternative activation. ChIP assays indicate that c-MYC directly regulates some genes associated with alternative activation, including SCARB1, ALOX15, and MRC1, whereas others, including CD209, are indirectly regulated by c-MYC. c-MYC up-regulates the IL-4 signaling mediators signal transducer and activator of transcription-6 and peroxisome proliferator-activated receptorgamma, is also expressed in tumor-associated macrophages, and its inhibition blocks the expression of protumoral genes including VEGF, MMP9, HIF 1alpha, and TGF-beta. We conclude that c-MYC is a key player in alternative macrophage activation, and is therefore a potential therapeutic target in pathologies related to these cells, including tumors. PMID- 22067386 TI - The repertoire of lambda light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1 44. AB - Monoclonal Ig light chains (LC) can be responsible for pathologic conditions in humans, as in systemic amyloid light amyloidosis. Protean clinical manifestations characterize this disorder with the most varied combination of symptoms generated by different degrees of diverse organ involvement. Kidney and heart are most frequently interested, with major heart involvement as the most relevant prognostic factor. The identification of the underlying mechanism involved in organ targeting is of major relevance for the pathobiology of this disorder. To this aim, we characterized the repertoire of variable region germline genes of lambda LC preferentially targeting the heart and compared it with the repertoire of LC that do not in a case-control study. We found that the repertoires were highly restricted, showing preferential use of the same few germline genes but with a different frequency pattern. A single gene, IGVL1-44, was found associated with a 5-fold increase in the odds of dominant heart involvement (after adjusting for confounders in a multivariable logistic model). These results support an involvement of LC genetics in the determination of organ targeting. Study of the characteristics of IGVL1-44-LC with, and of the minority without, heart involvement might lead to identification of LC/tissue interactions. PMID- 22067387 TI - Maturation and function of human dendritic cells are regulated by B lymphocytes. AB - Mature dendritic cells (DCs) are stimulators of T-cell immune response, whereas immature DCs support T-cell tolerance. Murine B cells can inhibit the production of IL-12 by DCs and thereby hinder the inflammatory response. Notwithstanding the importance of this modulation, only a few studies are available in humans. Here, we have developed an in vitro model of cocultures to assess its significance. We establish that human activated B cells restrained the development of monocytes into immature DCs and their differentiation into mature DCs. In addition, they decreased the density of HLA-DR from mature DCs, the expression of CD80 and CD86 coactivation molecules, the production of IL-12p70 required for antigen presentation and Th1 differentiation, and inhibited the DC-induced T-cell proliferation. These modulations were mediated by CD19(+)IgD(low)CD38(+)CD24(low)CD27(-) B cells and needed direct cell-to-cell contacts that involved CD62L for the control of CD80 and CD86 expression and a soluble factor for the control of IL-12 production. Moreover, mature DCs from patients with systemic lupus erythematosus displayed insensitivity to the regulation of IL-12. Overall, it appears that human B cells can regulate DC maturation and function and that inefficient B-cell regulation may influence an improper balance between an effector inflammatory response and tolerance induction. PMID- 22067388 TI - Tumor penetrative depth considers both the size of sentinel lymph node metastases and their location in relation to the nodal capsule. PMID- 22067389 TI - Phase II study of intraperitoneal paclitaxel plus cisplatin and intravenous paclitaxel plus bevacizumab as adjuvant treatment of optimal stage II/III epithelial ovarian cancer. AB - PURPOSE: Intraperitoneal (IP) cisplatin and intravenous (IV) or IP paclitaxel constitute a standard therapy for optimally debulked ovarian cancer. Bevacizumab prolongs progression-free survival (PFS) when included in first-line IV chemotherapy. In this study, the safety and feasibility of adding bevacizumab to a first-line IP regimen were assessed. PATIENTS AND METHODS: Treatment was as follows: paclitaxel 135 mg/m(2) IV over 3 hours day 1, cisplatin 75 mg/m(2) IP day 2, and paclitaxel 60 mg/m(2) IP day 8. Bevacizumab 15 mg/kg IV was given after paclitaxel on day 1 beginning in cycle 2. After six cycles of chemotherapy, bevacizumab was given every 3 weeks for 17 additional treatments. The primary end point was safety and tolerability determined by whether 60% of patients completed six cycles of IV/IP chemotherapy. RESULTS: Of 41 treated patients, 30 (73%) received six cycles of IV/IP chemotherapy and 35 (85%) received at least four cycles. Three (27%) of those who discontinued chemotherapy did so because of complications related to bevacizumab (hypertension, n = 2; perforation, n = 1). Grades 3 to 4 toxicities included neutropenia (34%), vasovagal syncope (10%), hypertension (7%), nausea/vomiting (7%), hypomagnesemia (7%), and abdominal pain (7%). There were three grade 3 small bowel obstructions (7%) during cycles 3, 9, and 15. One patient died following rectosigmoid anastomotic dehiscence during cycle 4. Estimated median PFS is 28.6 months (95% CI, 19.1 to 38.9 months). Three patients (7%) had IP port malfunction. CONCLUSION: The addition of bevacizumab to this IP regimen is feasible; however, bevacizumab may increase the risk of bowel obstruction/perforation. The observed median PFS is similar to that seen with IP/IV chemotherapy alone. PMID- 22067390 TI - Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. AB - PURPOSE: We developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer. PATIENTS AND METHODS: We sought validation by using RNA extracted from fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy. RESULTS: Risk of recurrence was significantly associated with RS (hazard ratio [HR] per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95). CONCLUSION: The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit. PMID- 22067391 TI - More than just an oncogene translocation and a kinase inhibitor: Kevin's story. PMID- 22067392 TI - When a decision must be made: role of computer modeling in clinical cancer research. PMID- 22067393 TI - Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. AB - PURPOSE: We studied BCR-ABL1 transcript levels in patients with chronic myeloid leukemia in chronic phase (CML-CP) at 3, 6, and 12 months after starting imatinib to identify molecular milestones that would predict for overall survival (OS) and other outcomes more reliably than serial marrow cytogenetics. PATIENTS AND METHODS: We analyzed 282 patients with CML-CP who received imatinib 400 mg/d as first-line therapy followed by dasatinib or nilotinib if treatment with imatinib failed. We used a receiver operating characteristic curve to identify the cutoffs in transcript levels at 3, 6, and 12 months that would best predict patient outcome. We validated our findings in an independent cohort of 95 patients treated elsewhere. RESULTS: Patients with transcript levels of more than 9.84% (n = 68) at 3 months had significantly lower 8-year probabilities of OS (56.9% v 93.3%; P < .001), progression-free survival, cumulative incidence of complete cytogenetic response, and complete molecular response than those with higher transcript levels. Similarly, transcript levels of more than 1.67% (n = 87) at 6 months and more than 0.53% (n = 93) at 12 months identified high-risk patients. However, transcript levels at 3 months were the most strongly predictive for the various outcomes. When we compared OS for the groups defined molecularly at 6 and 12 months with the usual cytogenetic milestones, categorization by transcript numbers was the only independent predictor for OS (relative risk, 0.207; P < .001 and relative risk, 0.158; P < .001, respectively). CONCLUSION: A single measurement of BCR-ABL1 transcripts performed at 3 months is the best way to identify patients destined to fare poorly, thereby allowing early clinical intervention. PMID- 22067394 TI - Individualizing follow-up for patients with early-stage melanoma. PMID- 22067395 TI - Minimizing therapy and maximizing outcomes in rectal cancer. PMID- 22067396 TI - Chemoresponsive liver hemangioma in a patient with a metastatic germ cell tumor. PMID- 22067397 TI - Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas. AB - PURPOSE: Ridaforolimus is an inhibitor of mammalian target of rapamycin, an integral component of the phosphatidyl 3-kinase/AKT signaling pathway, with early evidence of activity in sarcomas. This multicenter, open-label, single-arm, phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas. PATIENTS AND METHODS: Patients with metastatic or unresectable soft tissue or bone sarcomas received ridaforolimus 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks. The primary end point was clinical benefit response (CBR) rate (complete response or partial response [PR] or stable disease >= 16 weeks). Safety, progression-free survival (PFS), overall survival (OS), time to progression, and duration of response were also evaluated. RESULTS: A total of 212 patients were treated in four separate histologic cohorts. In this heavily pretreated population, 61 patients (28.8%) achieved CBR. Median PFS was 15.3 weeks; median OS was 40 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) confirmed response rate was 1.9%, with four patients achieving confirmed PR (two with osteosarcoma, one with spindle cell sarcoma, and one with malignant fibrous histiocytoma). Archival tumor protein markers analyzed were not correlated with CBR. Related adverse events were generally mild or moderate and consisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue. CONCLUSION: Single-agent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics. A phase III trial based on these data will further define ridaforolimus activity in sarcomas. PMID- 22067398 TI - Path toward prognostication and prediction: an evolving matrix. PMID- 22067399 TI - Optimizing the frequency of follow-up visits for patients treated for localized primary cutaneous melanoma. AB - PURPOSE: To develop more evidence-based guidelines for the frequency of patient follow-up after treatment of localized (American Joint Committee on Cancer [AJCC] stage I or II) melanoma. METHODS: We used data from Melanoma Institute Australia on an inception cohort of 3,081 consecutive patients first diagnosed with stage I or II melanoma between January 1985 and December 2009. Kaplan-Meier curves and Cox models were used to characterize the time course and predictors for recurrence and new primaries. We modeled the delay in diagnosis of recurrence or new primary as well as the number of monitoring visits required using two monitoring schedules: first, according to 2008 Australian and New Zealand guidelines and, second, with fewer visits, especially for those at lowest risk of recurrence. RESULTS: For every 1,000 patients beginning follow-up, 229 developed recurrence and 61 developed new primary within 10 years. There was only a small difference in modeled delay in diagnosis (extra 44.9 and 9.6 patients per 1,000 for recurrence and new primary, respectively, with delay greater than 2 months) using a schedule that requires far fewer visits (3,000 fewer visits per 1,000 patients) than recommended by current guidelines. AJCC substage was the most important predictor of recurrence, whereas age and date of primary diagnosis were important predictors of developing new primary. CONCLUSION: By providing less intensive monitoring, more efficient follow-up strategies are possible. Fewer visits with a more focused approach may address the needs of patients and clinicians to detect recurrent or new melanoma. PMID- 22067400 TI - Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. AB - PURPOSE: Neoadjuvant chemoradiotherapy for rectal cancer can result in complete disappearance of tumor and involved nodes. In patients without residual tumor on imaging and endoscopy (clinical complete response [cCR]) a wait-and-see-policy (omission of surgery with follow-up) might be considered instead of surgery. The purpose of this prospective cohort study was to evaluate feasibility and safety of a wait-and-see policy with strict selection criteria and follow-up. PATIENTS AND METHODS: Patients with a cCR after chemoradiotherapy were prospectively selected for the wait-and-see policy with magnetic resonance imaging (MRI) and endoscopy plus biopsies. Follow-up was performed 3 to 6 monthly and consisted of MRI, endoscopy, and computed tomography scans. A control group of patients with a pathologic complete response (pCR) after surgery was identified from a prospective cohort study. Functional outcome was measured with the Memorial Sloan Kettering Cancer Center (MSKCC) bowel function questionnaire and Wexner incontinence score. Long-term outcome was estimated by using Kaplan-Meier curves. RESULTS: Twenty-one patients with cCR were included in the wait-and-see policy group. Mean follow-up was 25 +/- 19 months. One patient developed a local recurrence and had surgery as salvage treatment. The other 20 patients are alive without disease. The control group consisted of 20 patients with a pCR after surgery who had a mean follow-up of 35 +/- 23 months. For these patients with a pCR, cumulative probabilities of 2-year disease-free survival and overall survival were 93% and 91%, respectively. CONCLUSION: A wait-and-see policy with strict selection criteria, up-to-date imaging techniques, and follow-up is feasible and results in promising outcome at least as good as that of patients with a pCR after surgery. The proposed selection criteria and follow-up could form the basis for future randomized studies. PMID- 22067402 TI - Older women with breast cancer: slow progress, great opportunity, now is the time. PMID- 22067401 TI - RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors. AB - PURPOSE: RAF inhibitors are effective against melanomas with BRAF V600E mutations but may induce keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cSCCs). The potential of these agents to promote secondary malignancies is concerning. We analyzed cSCC and KA lesions for genetic mutations in an attempt to identify an underlying mechanism for their formation. METHODS: Four international centers contributed 237 KA or cSCC tumor samples from patients receiving an RAF inhibitor (either vemurafenib or sorafenib; n = 19) or immunosuppression therapy (n = 53) or tumors that developed spontaneously (n = 165). Each sample was profiled for 396 known somatic mutations across 33 cancer related genes by using a mass spectrometric-based genotyping platform. RESULTS: Mutations were detected in 16% of tumors (38 of 237), with five tumors harboring two mutations. Mutations in TP53, CDKN2A, HRAS, KRAS, and PIK3CA were previously described in squamous cell tumors. Mutations in MYC, FGFR3, and VHL were identified for the first time. A higher frequency of activating RAS mutations was found in tumors from patients treated with an RAF inhibitor versus populations treated with a non-RAF inhibitor (21.1% v 3.2%; P < .01), although overall mutation rates between treatment groups were similar (RAF inhibitor, 21.1%; immunosuppression, 18.9%; and spontaneous, 17.6%; P = not significant). Tumor histology (KA v cSCC), tumor site (head and neck v other), patient age (<= 70 v > 70 years), and sex had no significant impact on mutation rate or type. CONCLUSION: Squamous cell tumors from patients treated with an RAF inhibitor have a distinct mutational profile that supports a mechanism of therapy-induced tumorigenesis in RAS-primed cells. Conceivably, cotargeting of MEK together with RAF may reduce or prevent formation of these tumors. PMID- 22067403 TI - From node to pathway blockade: lessons learned from targeting mammalian target of rapamycin. PMID- 22067404 TI - Nomogram for predicting the benefit of adjuvant chemoradiotherapy for resected gallbladder cancer. AB - PURPOSE: Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. METHODS: Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. RESULTS: A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser-based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. CONCLUSION: A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT. PMID- 22067405 TI - Induction of cutaneous squamous cell carcinomas by RAF inhibitors: cause for concern? PMID- 22067406 TI - Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue. AB - PURPOSE: Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples. PATIENTS AND METHODS: A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery. RESULTS: The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001). CONCLUSION: This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples. PMID- 22067407 TI - Improvement in breast cancer outcomes over time: are older women missing out? AB - PURPOSE: Women aged >= 75 years account for 40,000 breast cancers/yr and are the most rapidly growing demographic. Recent data demonstrated that breast cancer death rates in the US population are declining, but it is not known whether death rates have declined similarly for older and younger women. We examined the following two outcomes: the rate of breast cancer death in the general population and the risk of breast cancer death in newly diagnosed patients, and we compared change over time in these outcomes for older versus younger women. METHODS: By using data from National Vital Statistics Reports that spanned from 1990 to 2007, the yearly change in the age-specific rate of breast cancer death was characterized with linear regression. With the use of the Surveillance, Epidemiology, and End Results nine-registry cohort that spanned from 1980 to 1997, the yearly change in age-specific risk of breast cancer death was characterized by using competing-risks regression adjusted for race and stage. RESULTS: Relative to 1990, the rate of breast cancer death in the general population decreased by 2.5%/yr for women age 20 to 49 years, 2.1%/yr for women age 50 to 64 years, 2.0%/yr for women age 65 to 74 years, and 1.1%/yr for women age >= 75 years. From 1980 to 1997, the adjusted risk of breast cancer death in newly diagnosed patients decreased by 3.6%/yr for women age less than 75 years versus 1.3%/yr for women age >= 75 years (P < .001). Over this time interval, the 10-year absolute risk of breast cancer death decreased by 15.3% for women age 50 to 64 years (from 31.9% to 16.6%) but by only 7.5% (from 24.8% to 17.4%) for women age >= 75 years. CONCLUSION: Breast cancer outcomes have preferentially improved in women age less than 75 years. Focused research is needed to improve outcomes in older women. PMID- 22067408 TI - Esophageal cancer: a critical evaluation of systemic second-line therapy. AB - The objective of this article was to review clinical trials that used antineoplastic second-line chemotherapy and/or targeted therapies in patients with esophageal cancer after first-line therapy. Computerized (MEDLINE) and manual searches were performed to identify articles published on this topic between 1996 and 2011. Twenty-five published trials and four abstracts presented at scientific meetings were identified. A total of 10 trials included only patients with squamous cell carcinomas (SCCs), four focused exclusively on adenocarcinoma (AC), the remaining 15 studies included both SCC and AC. The majority of trials (17 of 29) used docetaxel in combination with platinum analogs, eight used single-agent cytotoxic chemotherapy, and six evaluated targeted therapies. The numbers of patients were relatively small, ranging from eight to 55 patients. The response rates were generally low (between 0% and 39%), with only two small studies reporting objective responses of 50% and 63%, respectively. Time to progression ranged from 1.4 to 6.2 months, and the overall survival was disappointing at 4.0 to 11.4 months. Approximately 40% of patients who experience progressive disease after first-line chemotherapy are able to undergo second-line treatment. On the basis of data published so far, no standard second-line therapy has emerged. Future research will need to focus on individual therapy strategies such as genetic receptor mutations to increase the therapeutic outcome. PMID- 22067409 TI - Balloon atrial septostomy and pre-operative brain injury in neonates with transposition of the great arteries: a systematic review and a meta-analysis. AB - OBJECTIVE: To perform a systematic review and a meta-analysis of the effects of balloon atrial septostomy on peri-operative brain injury in neonates with transposition of the great arteries. DATA SOURCE: We conduct a systematic review of the literature to identify all observational studies that included neonates born with transposition of the great arteries who had peri-operative evidence of brain injury. STUDY SELECTION AND DATA EXTRACTION: The search strategy produced three prospective and two retrospective cohort studies investigating the association between balloon atrial septostomy and brain injury totalling 10,108 patients. In two studies, the outcome was represented by the presence of a coded diagnosis of a clinically evident stroke at discharge, whereas in three studies the outcome was represented by the finding of pre-operative brain injury identified by magnetic resonance scans. DATA SYNTHESIS: The overall brain injury rate for neonates who underwent balloon atrial septostomy versus control patients was 60 of 2273 (2.6%) versus 45 of 7835 (0.5%; pooled odds ratio, 1.90; 95% confidence intervals, 0.93-3.89; p = 0.08). A subgroup analysis of the three studies that used pre-operative brain injury as the primary outcome found no significant association between balloon atrial septostomy and brain injury (pooled odds ratio, 2.70; 95% confidence intervals, 0.64-11.33; p = 0.17). Balloon atrial septostomy frequency was 22.4% (2273 of 10,108), with reported rates ranging from 20% to 75%. CONCLUSION: Our analysis shows that balloon atrial septostomy is not associated with increased odds for peri-operative brain injury. Balloon atrial septostomy should still be used for those patients with significant hypoxaemia, haemodynamic instability, or both. PMID- 22067410 TI - Phosphodiesterase 5 inhibition with sildenafil reverses exercise oscillatory breathing in chronic heart failure: a long-term cardiopulmonary exercise testing placebo-controlled study. AB - AIMS: Exercise oscillatory breathing (EOB) is a ventilatory abnormality that occurs in ~20% of heart failure (HF) patients and carries a very unfavourable prognosis. Pulmonary vasoconstriction has been suggested to be involved in this disorder. We hypothesized that modulation of pulmonary vascular hypertone by oversignalling of the nitric oxide pathway with phosphodiesterase 5 (PDE5) inhibition might be beneficial. Accordingly, we performed a 1-year pilot trial with sildenafil in patients with HF and EOB. METHODS AND RESULTS: Among 122 HF cases, 32 presented with EOB during cardiopulmonary exercise testing (CPX) and were randomized to receive placebo (n = 16) or sildenafil (n = 16) at the dose of 50 mg three times a day, in addition to their current antifailure treatment. CPX derived variables and pulmonary haemodynamics were assessed at 6 and 12 months. Sildenafil reversed EOB in 87% of patients at 6 months and 93% at 1 year, respectively (P < 0.01). This effect was accompanied by an improvement in functional performance (peak VO(2); from 9.6 to 12.4 and 13.2 mL/min/kg; P < 0.01) and exercise ventilation efficiency (ventilation to CO(2) production slope; from 41.1 to 32.7 and 31.5; P < 0.01). Chronic treatment with PDE5 inhibition significantly decreased pulmonary capillary wedge pressure (from 21 to 14 and 14 mmHg), mean pulmonary artery pressure (PAP; from 34.8 to 23 and 24 mmHg), and pulmonary vascular resistance (PVR; from 360 to 270 and 266 dyne/s/cm(5)) compared with placebo (P < 0.01 for each comparison). On exploratory analysis, there was a correlation between PAP and PVR and the decrease in EOB in the treatment group. Placebo did not alter any of the aforementioned variables. CONCLUSIONS: PDE5 inhibition in HF patients with EOB offers the dual advantage of improving functional capacity and modulating the EOB pattern. PAP and PVR reduction seem to underlie the correction of the breathing disorder. Whether reversal of this unfavourable prognostic signal can affect survival remains unconfirmed at the moment. PMID- 22067411 TI - Dental caries area of rat molar expanded by cigarette smoke exposure. AB - OBJECTIVES: Passive smoking is the involuntary inhalation of cigarette smoke (CS) and has an adverse impact on oral health. We examined the effect of CS exposure on caries risk and experimental dental caries. METHODS: Experimental dental caries was induced in rat maxillary molars which were inoculated orally with Streptococcus mutans MT8148 and maintained on a cariogenic diet (diet 2000) and high sucrose water during the experimental period. CS-exposed rats were intermittently housed in an animal chamber with whole-body exposure to CS until killed. Whole saliva was collected before CS exposure (day 0) and for 30 days after the start of CS exposure. Saliva secretion was stimulated by administration of isoproterenol and pilocarpine after anesthesia. Maxillary molars were harvested on day 31. RESULTS: The increase in body weight of the CS-exposed rats was less than that of the control rats. Salivary flow rate, concentration of S. mutans in the stimulated saliva and caries activity score did not significantly differ between 0 and 30 days after the start of CS exposure. Histological examination of the caries-affected area on maxillary molars 30 days after CS exposure showed expansion compared to control rats. In the electron probe microanalysis, no differences were observed between the mineral components of the CS-exposed teeth and the control teeth. CONCLUSION: These results suggest that CS exposure expands the caries-affected area in the maxillary molars of the rat. PMID- 22067412 TI - Phase-specific plasticity of synaptic structures in the somatosensory cortex of living mice during neuropathic pain. AB - BACKGROUND: Postsynaptic dendritic spines in the cortex are highly dynamic, showing rapid morphological changes including elongation/retraction and formation/elimination in response to altered sensory input or neuronal activity, which achieves experience/activity-dependent cortical circuit rewiring. Our previous long-term in vivo two-photon imaging study revealed that spine turnover in the mouse primary somatosensory (S1) cortex markedly increased in an early development phase of neuropathic pain, but was restored in a late maintenance phase of neuropathic pain. However, it remains unknown how spine morphology is altered preceding turnover change and whether gain and loss of presynaptic boutons are changed during neuropathic pain. FINDINGS: Here we used short-term (2 hour) and long-term (2-week) time-lapse in vivo two-photon imaging of individual spines and boutons in the S1 cortical layer 1 of the transgenic mice expressing GFP in pyramidal neurons following partial sciatic nerve ligation (PSL). We found in the short-term imaging that spine motility (Delta length per 30 min) significantly increased in the development phase of neuropathic pain, but returned to the baseline in the maintenance phase. Moreover, the proportion of immature (thin) and mature (mushroom) spines increased and decreased, respectively, only in the development phase. Long-term imaging data showed that formation and elimination of boutons moderately increased and decreased, respectively, during the first 3 days following PSL and was subsequently restored. CONCLUSIONS: Our results indicate that the S1 synaptic structures are rapidly destabilized and rearranged following PSL and subsequently stabilized in the maintenance phase of neuropathic pain, suggesting a novel therapeutic target in intractable chronic pain. PMID- 22067413 TI - The uncertain consequences of transferring bacterial strains between laboratories - rpoS instability as an example. AB - BACKGROUND: Microbiological studies frequently involve exchanges of strains between laboratories and/or stock centers. The integrity of exchanged strains is vital for archival reasons and to ensure reproducible experimental results. For at least 50 years, one of the most common means of shipping bacteria was by inoculating bacterial samples in agar stabs. Long-term cultures in stabs exhibit genetic instabilities and one common instability is in rpoS. The sigma factor RpoS accumulates in response to several stresses and in the stationary phase. One consequence of RpoS accumulation is the competition with the vegetative sigma factor sigma70. Under nutrient limiting conditions mutations in rpoS or in genes that regulate its expression tend to accumulate. Here, we investigate whether short-term storage and mailing of cultures in stabs results in genetic heterogeneity. RESULTS: We found that samples of the E. coli K-12 strain MC4100TF exchanged on three separate occasions by mail between our laboratories became heterogeneous. Reconstruction studies indicated that LB-stabs exhibited mutations previously found in GASP studies in stationary phase LB broth. At least 40% of reconstructed stocks and an equivalent proportion of actually mailed stock contained these mutations. Mutants with low RpoS levels emerged within 7 days of incubation in the stabs. Sequence analysis of ten of these segregants revealed that they harboured each of three different rpoS mutations. These mutants displayed the classical phenotypes of bacteria lacking rpoS. The genetic stability of MC4100TF was also tested in filter disks embedded in glycerol. Under these conditions, GASP mutants emerge only after a 3-week period. We also confirm that the intrinsic high RpoS level in MC4100TF is mainly due to the presence of an IS1 insertion in rssB. CONCLUSIONS: Given that many E. coli strains contain high RpoS levels similar to MC4100TF, the integrity of such strains during transfers and storage is questionable. Variations in important collections may be due to storage-transfer related issues. These results raise important questions on the integrity of bacterial archives and transferred strains, explain variation like in the ECOR collection between laboratories and indicate a need for the development of better methods of strain transfer. PMID- 22067414 TI - Emotional and symptomatic reactivity to stress in individuals at ultra-high risk of developing psychosis. AB - BACKGROUND: The stress-vulnerability model of psychosis continues to be influential. The aim of this study was to compare emotional and symptomatic responses to stress in individuals at ultra-high risk (UHR) of developing psychosis, in age- and gender-matched healthy controls, and in patients with non affective psychosis. METHOD: A total of 27 UHR, 27 psychotic and 27 healthy individuals completed the experience sampling method, an ambulant diary technique, where they were required to fill in self-assessment questions about their emotions, symptoms and perceived stress at semi-random times of the day for 6 days. Quesionnaire and interview assessments were also completed. RESULTS: Multilevel regression analyses showed that individuals at UHR of developing psychosis reported greater negative emotions in response to stress than the healthy individuals. Against the initial hypotheses, the UHR individuals also experienced greater emotional reactivity to stress when compared with the patient group. No significant differences were observed between the patients and the non clinical sample. Stress measures significantly predicted the intensity of psychotic symptoms in UHR individuals and patients, but the extent of this did not significantly differ between the groups. CONCLUSIONS: Individuals at UHR of developing psychosis may be particularly sensitive to everyday stressors. This effect may diminish after transition to psychosis is made and in periods of stability. Subtle increases in psychotic phenomena occur in response to stressful events across the continuum of psychosis. PMID- 22067415 TI - Predictive value and safety of intraoperative neurophysiological monitoring with motor evoked potentials in glioma surgery. AB - BACKGROUND: Resection of gliomas in or adjacent to the motor system is widely performed with intraoperative neuromonitoring (IOM). Despite the fact that data on the safety of IOM are available, the significance and predictive value of the procedure are still under discussion. Moreover, cases of false-negative monitoring affect the surgeon's confidence in IOM. OBJECTIVE: To examine cases of false-negative IOM to reveal structural explanations. METHODS: Between 2007 and 2010, we resected 115 consecutive supratentorial gliomas in or close to eloquent motor areas using direct cortical stimulation for monitoring of motor evoked potentials (MEPs). The monitoring data were reviewed and related to new postoperative motor deficit and postoperative imaging. Clinical outcomes were assessed during follow-up. RESULTS: Monitoring of MEPs was successful in 112 cases (97.4%). Postoperatively, 30.3% of patients had a new motor deficit, which remained permanent in 12.5%. Progression-free follow-up was 9.7 months (range, 2 weeks-40.6 months). In 65.2% of all cases, MEPs were stable throughout the operation, but 8.9% showed a new temporary motor deficit, whereas 4.5% (5 patients) presented with permanently deteriorated motor function representing false-negative monitoring at first glance. However, these cases were caused by secondary hemorrhage, ischemia, or resection of the supplementary motor area. CONCLUSION: Continuous MEP monitoring provides reliable monitoring of the motor system, influences the course of operation in some cases, and has to be regarded as the standard for IOM of the motor system. In our series, we found no false negative MEP results. PMID- 22067416 TI - Conservative management of vestibular schwannoma--a prospective cohort study: treatment, symptoms, and quality of life. AB - BACKGROUND: One hundred ninety-three patients with sporadic unilateral vestibular schwannoma given conservative management were enrolled in a prospective study. OBJECTIVE: To evaluate the efficacy of conservative management and to determine the effect of an initial conservative management on the quality of life (QOL) and severity of audio vestibular symptoms. METHODS: The patients underwent magnetic resonance imaging scans, clinical examination, and QOL assessment by 2 validated questionnaires, the Short Form-36 (SF-36) and Glasgow Benefit Inventory (GBI). Using regression analysis of clustered data, we analyzed possible associations between tumor growth and symptoms and tested whether our earlier finding that vertigo is associated with reduced QOL could be verified. RESULTS: The median follow-up time was 43 months (range, 9-115 months; SD, 21.48 months). Results are based on 703 clinical controls and 642 (SF-36) and 638 (GBI) questionnaires. Seven patients were lost to follow-up. Approximately 40% of patients were in need of treatment during follow-up. We found a statistically significant association between tinnitus and vertigo and tumor growth. Vertigo was found to significantly reduce QOL. There was a significant drop in the Social Function subscales of both SF-36 and GBI, possibly attributable to progressive hearing loss. Otherwise, there was no overall trend toward any change in QOL during the observation period. In addition, QOL seemed to be little affected by treatment. CONCLUSION: There was a small but statistically significant improvement in vestibular complaints and no change in the occurrence of tinnitus. Except for hearing loss caused by surgery, treatment did not affect symptoms or QOL significantly. Growth was associated with the occurrence of tinnitus and balance problems. PMID- 22067417 TI - Surgery of insular nonenhancing gliomas: volumetric analysis of tumoral resection, clinical outcome, and survival in a consecutive series of 66 cases. AB - BACKGROUND: Despite intraoperative technical improvements, the insula remains a challenging area for surgery because of its critical relationships with vascular and neurophysiological functional structures. OBJECTIVE: To retrospectively investigate the morbidity profile in insular nonenhancing gliomas, with special emphasis on volumetric analysis of tumoral resection. METHODS: From 2000 to 2010, 66 patients underwent surgery. All surgical procedures were conducted under cortical-subcortical stimulation and neurophysiological monitoring. Volumetric scan analysis was applied on T2-weighted magnetic resonance images (MRIs) to establish preoperative and postoperative tumoral volume. RESULTS: The median preoperative tumor volume was 108 cm. The median extent of resection was 80%. The median follow-up was 4.3 years. An immediate postoperative worsening was detected in 33.4% of cases; a definitive worsening resulted in 6% of cases. Patients with extent of resection of > 90% had an estimated 5-year overall survival rate of 92%, whereas those with extent of resection between 70% and 90% had a 5-year overall survival rate of 82% (P < .001). The difference between preoperative tumoral volumes on T2-weighted MRI and on postcontrast T1-weighted MRI ([T2 - T1] MRI volume) was computed to evaluate the role of the diffusive tumoral growing pattern on overall survival. Patients with preoperative volumetric difference < 30 cm demonstrated a 5-year overall survival rate of 92%, whereas those with a difference of > 30 cm had a 5-year overall survival rate of 57% (P = .02). CONCLUSION: With intraoperative cortico-subcortical mapping and neurophysiological monitoring, a major resection is possible with an acceptable risk and a significant result in the follow-up. PMID- 22067418 TI - Predicting long-term remission by measuring immediate postoperative growth hormone levels and oral glucose tolerance test in acromegaly. AB - BACKGROUND: The suppression of the growth hormone (GH) on an oral glucose tolerance test (OGTT) has been accepted as the most reliable parameter for determining remission of acromegaly. OBJECTIVE: To evaluate the role of immediate postoperative GH level and 1-week postoperative OGTT as early predictive tools of long-term surgical remission. METHODS: One hundred ninety-four acromegalic patients who received transsphenoidal tumor resection and were followed up for > 1.5 years (3.80 +/- 0.17 years) with at least 3 postoperative OGTTs were evaluated. Level of GH was measured 2, 6, 12, 18, 24, 48, and 72 hours postoperatively, and an OGTT was performed 1 week after surgery, every 6 months for the first 3 years, and annually thereafter. RESULTS: One hundred seventy seven patients underwent gross total resection; long-term remission was achieved in 153. The GH level at 24 hours after surgery showed the highest predictive power for long-term remission. Long-term remission was maintained in 125/127 (98.4%) patients who had nadir GH levels < 1.0 MUg/L on an early postoperative OGTT. However, when nadir GH levels were > 1.0 MUg/L on an early postoperative OGTT, long-term remission was observed in 28 patients (28 of 67, 41.8%) in a delayed fashion. One-week postoperative OGTT had a sensitivity of 81.7% and specificity of 95.1% for predicting remission. CONCLUSION: Immediate postoperative GH level is a very good predictor of long-term outcome in acromegaly. One-week postoperative OGTT is also a good predictor with high specificity. These findings may provide critical information for the determination of adjuvant treatment after surgery. PMID- 22067420 TI - Impact of changes in intraoperative somatosensory evoked potentials on stroke rates after clipping of intracranial aneurysms. AB - BACKGROUND: Somatosensory evoked potential (SSEP) monitoring is used during intracranial aneurysm surgery to track the effects of anesthesia, surgical manipulation, and temporary clipping. OBJECTIVE: To present the outcomes of 663 consecutive patients (691 cases) treated surgically for intracranial aneurysms who underwent intraoperative SSEP monitoring and to analyze the sensitivity and specificity of significant SSEP changes in predicting postoperative stroke. METHODS: Of 691 surgeries analyzed, 403 (391 anterior circulation, 12 posterior circulation) were unruptured aneurysms and 288 (277 anterior, 11 posterior) were ruptured. Postoperatively, symptomatic patients underwent computed tomography imaging. Positive predictive value, negative predictive value, sensitivity, and specificity were calculated with a Fisher exact test (2-tailed P value). RESULTS: Changes in SSEP occurred in 45 of 691 cases (6.5%): 16 of 403 (4.0%) in unruptured aneurysms and 29 of 288 (10%) in ruptured aneurysms. In unruptured aneurysms, reversible SSEP changes were associated with a 20% stroke rate, but irreversible changes were associated with an 80% stroke rate. In ruptured aneurysms, however, reversible changes were associated with a 12% stroke rate, and irreversible changes were associated with a 42% stroke rate. The overall accuracy of SSEP changes in predicting postoperative stroke was as follows: positive predictive value, 30%; negative predictive value, 94%; sensitivity, 25%; and specificity, 95%. CONCLUSION: Intraoperative SSEP changes are more reliable in unruptured aneurysm cases than in ruptured cases. Whereas irreversible changes in unruptured cases were associated with an 80% stroke rate, such changes in ruptured cases did not have any adverse ischemic sequelae in 58% of patients. This information is helpful during the intraoperative assessment of reported SSEP changes. PMID- 22067421 TI - Effectiveness of repeat glycerol rhizotomy in treating recurrent trigeminal neuralgia. AB - BACKGROUND: Percutaneous glycerol rhizotomy (GR) is used to treat trigeminal neuralgia (TN), with satisfactory pain relief lasting 2 to 3 years in most patients after the first intervention. The efficacy of subsequent GRs, however, has not been studied. OBJECTIVE: To compare the pain relief and durability achieved by the first GR with those obtained after subsequent GRs in a retrospective cohort of TN patients. METHODS: Between 1998 and 2010, 548 patients with TN underwent 708 GRs. After exclusions, 430 initial GRs (GR1) and 114 subsequent GRs (GR2+) were compared in terms of initial pain relief, durability, sensory change, and complications. Durability was assessed by determining median time to treatment failure for all GRs achieving complete pain relief without medications (n = 375: 264 failures, 111 censored). Predictors of initial pain relief were assessed by logistic regression, and predictors of failure were assessed by Cox regression analysis. RESULTS: After GR1, pain relief results were as follows: 285 patients (66%) were pain free without medications, 26 (6%) were pain free with medications, 66 (15%) improved, and 53 (12%) were unchanged. After GR2+, results were as follows: 90 patients (79%) were pain free without medications, 6 (5%) were pain free with medications, 7 (6%) improved, and 11 (10%) were unchanged (P = .03). Median time to treatment failure was 26 months after GR1 and 25 months after GR2+ (P = .34). On multivariate analysis, prior GR was a positive predictor of initial pain relief (odds ratio, 2.067; 95% confidence interval, 1.243-3.437; P = .005) and had no effect on durability. CONCLUSION: TN patients experienced greater pain relief and equivalent durability after GR2+ beyond the initial treatment. PMID- 22067422 TI - Characterization of the supplementary motor area syndrome and seizure outcome after medial frontal lobe resections in pediatric epilepsy surgery. AB - BACKGROUND: In adults, resection of the medial frontal lobe has been shown to result in supplementary motor area (SMA) syndrome, a disorder characterized by transient motor impairment. Studies examining the development of SMA syndrome in children, however, are wanting. OBJECTIVE: To characterize the development of SMA syndrome and to analyze seizure outcomes after surgery in the medial frontal lobe for medically intractable epilepsy. METHODS: Thirty-nine patients with medically intractable epilepsy who underwent surgery in the medial frontal lobe were reviewed retrospectively. The progression of neurological impairment and seizure outcome after surgery was recorded, and the extent of cortex resected was analyzed. RESULTS: After resection in the region of the SMA, 23 patients (59%) developed postoperative neurological impairment; 17 (74%) were identified as SMA syndrome. No neurological impairment was found after surgery in 16 patients (41%). Six patients (15%) experienced permanent neurological impairment. The majority of patients (82%) who developed SMA syndrome had resolution of their symptoms by 1 month postoperatively. Preoperative magnetic resonance imaging finding of lesional cases was associated with a significantly decreased likelihood of developing SMA syndrome (P = .02). Seizure outcome was favorable after surgery in most patients. CONCLUSION: Surgery for medically intractable epilepsy in the region of the medial frontal cortex is effective and associated with reversible neurological impairment in children. All patients had resolution of their SMA syndrome by 6 months postoperatively. PMID- 22067423 TI - Ventricular catheter location and the clearance of intraventricular hemorrhage. AB - BACKGROUND: There is no consensus regarding optimal position of an external ventricular drain (EVD) with regard to clearance of intraventricular hemorrhage (IVH). OBJECTIVE: To assess the hypothesis that EVD laterality may influence the clearance of blood from the ventricular system with and without administration of thrombolytic agent. METHODS: The EVD location was assessed in 100 patients in 2 Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR IVH) phase II trials assessing the safety and dose optimization of thrombolysis through the EVD to accelerate the clearance of obstructive IVH. Laterality of catheter was correlated with clearance rates. RESULTS: Clearance of IVH over the first 3 days was significantly greater when thrombolytic compared with placebo was administered regardless of catheter laterality (P < .005; 95% confidence interval, -14.0 to -4.14 for contralateral EVD and -24.7 to -5.44 for ipsilateral EVD). When thrombolytic was administered, there was a trend toward more rapid clearance of total IVH through an EVD placed on the side of dominant intraventricular blood compared with an EVD on the side with less blood (P = .09; 95% confidence interval, -9.62 to 0.69). This was not true when placebo was administered. Clearance of third and fourth ventricular blood was unrelated to EVD laterality. CONCLUSION: It is possible that placement of EVD may be optimized to enhance the clearance of total IVH if lytic agents are used. Catheters on either side can clear the third and fourth ventricles with equal efficiency. PMID- 22067424 TI - Prognostic value of pulmonary dead space in patients with the acute respiratory distress syndrome. AB - A study published in the previous issue of Critical Care demonstrates that measurement of the pulmonary dead-space fraction is superior to hypoxemia as an indicator of a favorable physiologic response to prone positioning in patients with severe acute respiratory distress syndrome. These results add to the growing evidence supporting the clinical and research value of measuring pulmonary dead space in patients with acute respiratory distress syndrome and using this pulmonary physiologic end-point as one indicator of a favorable response to therapy. PMID- 22067426 TI - The performance of the leveraged buyout of the Hospital Corporation of America, Inc. AB - BACKGROUND: A leveraged buyout (LBO) is a type of corporate reorganization and acquisition practice whereby private investors borrow a substantial amount of debt to acquire a firm by buying back its publicly held stock to go private. The Hospital Corporation of America, Inc. (HCA), went through its second LBO in July of 2006. A prior study on the performance changes of the first LBO found no significant changes in revenues, expenses, or profitability. PURPOSES: In this study, we evaluated the changes in performance measures for HCA hospitals during the second LBO period. We looked at the effect of the LBO on financial and operational performance indicators, controlling for market and hospital characteristics. METHODOLOGY: We identified 121 urban HCA hospitals that consistently reported data over a 4-year window from 1 year pre-LBO to 3 years post-LBO and evaluated their study performance changes during the period. Primary data for operational and financial measures are derived from Health Care Cost Report Information System data sets. FINDINGS: On the basis of this study, the LBO led to significant increases in cash flow margin, net patient revenues, and total asset turnover ratio. It also increased operating expenses significantly. However, it was not associated with changes in labor costs, staffing, and capital investment. PRACTICE IMPLICATIONS: The management of publicly traded hospitals that consider an LBO should develop operating strategies to maintain a strong cash flow performance and find ways to boost patient volume. It also needs to determine if it would be able to continue investing in its facilities to keep physicians and patients loyal and to keep investing in the training and retention of employees, which ultimately improves the quality of care and enhances operational efficiency. PMID- 22067427 TI - Work environment factors other than staffing associated with nurses' ratings of patient care quality. AB - BACKGROUND: The impact of registered nurse (RN) staffing on patient care quality has been extensively studied. Identifying additional modifiable work environment factors linked to patient care quality is critical as the projected shortage of approximately 250,000 RNs over the next 15 years will limit institutions' ability to rely on RN staffing alone to ensure high-quality care. PURPOSE: We examined the association between RNs' ratings of patient care quality and several novel work environment factors adjusting for the effects of two staffing variables: reported patient-to-RN ratios and ratings of staffing adequacy. METHODOLOGY: We used a cross-sectional, correlational design and a mailed survey to collect data in 2009 from a national sample of RNs (n = 1,439) in the United States. A multivariate logistic regression was used to analyze the data. FINDINGS: Workgroup cohesion, nurse-physician relations, procedural justice, organizational constraints, and physical work environment were associated with RNs' ratings of quality, adjusting for staffing. Furthermore, employment in a Magnet hospital and job satisfaction were positively related to ratings of quality, whereas supervisory support was not. PRACTICE IMPLICATIONS: Our evidence demonstrates the importance of considering RN work environment factors other than staffing when planning improvements in patient care quality. Health care managers can use the results of our study to strategically allocate resources toward work environment factors that have the potential to improve quality of care. PMID- 22067428 TI - Are utilities bounded at 1.0? Implications for statistical analysis and scale development. PMID- 22067429 TI - Calculating utility decrements associated with an adverse event: marginal Tobit and CLAD coefficients should be used with caution. AB - BACKGROUND: When calculating the decreases in health utility associated with adverse events, often a number of respondents achieve the upper utility bound of 1. "Marginal" Tobit or CLAD coefficients have been used to account for this. These are calculated by using a Tobit or a CLAD model to estimate the decrease in a latent unbounded variable associated with the event or condition, then to multiply by the proportion of respondents falling below 1 in order to transform back to the utility scale. OBJECTIVE: & METHODS: Starting with the Tobit model, we show mathematically that this procedure is not valid, when calculating decreases in utility associated with binary events. We then generalize the result to the CLAD model. A selection of published studies is used to illustrate the bias in the marginal Tobit decrements. RESULTS: The degree of bias is more severe the greater the decrease in utility associated with the event, and the larger the proportion of individuals at the upper ceiling.In the examples studied, the degree of bias was often greater than 10%. We provide the correct formula for calculating the utility decrement. CONCLUSIONS: The marginal Tobit and CLAD coefficients should not be used as estimates of a utility decrement corresponding to an adverse event or health condition unless the coefficients are small in absolute value, or if the proportion of individuals at the upper utility bound is small. In other settings, the corrected formula or alternative regression methods (e.g. linear models of mean utility) should be considered. PMID- 22067430 TI - The relative importance of quality of care information when choosing a hospital for surgical treatment: a hospital choice experiment. AB - OBJECTIVE: To assess the impact of quality of care and other hospital information on patients' choices between hospitals. METHODS: 665 former surgical patients were invited to respond to an Internet-based questionnaire including a choice based conjoint analysis. Each patient was presented with 12 different comparisons of 2 hospitals, with each hospital characterized by 6 attributes containing 2 levels. Hospital attributes were included if frequently reported by patients as most important for future hospital choices. These included both general hospital information (e.g., atmosphere), information on quality of care (e.g., percentage of patients with "textbook outcome"), and surgery-specific information (e.g., possibility for minimally invasive procedure). Hierarchial Bayes estimation was used to estimate the utilities for each attribute level for each patient. Based on the ranges of these utilities, the relative importance of each hospital attribute was determined for each participant as a measure of the impact on patients' choices. RESULTS: 308 (46.3%) questionnaires were available for analysis. Of the hospital attributes that patients considered, surgery-specific information on average had the highest relative importance (25.7 [23.9-27.5]), regardless of gender, age, and education. Waiting time and hospital atmosphere were considered least important. The attribute concerning the percentage of patients with "textbook outcomes" had the second greatest impact (18.3 [16.9 19.6]), which was similar for patients with different adverse outcome experience. CONCLUSIONS: Surgery-specific and quality of care information are more important than general information when patients choose between hospitals. PMID- 22067431 TI - Varieties of uncertainty in health care: a conceptual taxonomy. AB - Uncertainty is a pervasive and important problem that has attracted increasing attention in health care, given the growing emphasis on evidence-based medicine, shared decision making, and patient-centered care. However, our understanding of this problem is limited, in part because of the absence of a unified, coherent concept of uncertainty. There are multiple meanings and varieties of uncertainty in health care that are not often distinguished or acknowledged although each may have unique effects or warrant different courses of action. The literature on uncertainty in health care is thus fragmented, and existing insights have been incompletely translated to clinical practice. This article addresses this problem by synthesizing diverse theoretical and empirical literature from the fields of communication, decision science, engineering, health services research, and psychology and developing a new integrative conceptual taxonomy of uncertainty. A 3-dimensional taxonomy is proposed that characterizes uncertainty in health care according to its fundamental sources, issues, and locus. It is shown how this new taxonomy facilitates an organized approach to the problem of uncertainty in health care by clarifying its nature and prognosis and suggesting appropriate strategies for its analysis and management. PMID- 22067433 TI - Conversion of the Mini-Mental State Examination to the International Classification of Functioning, Disability and Health terminology and scoring system. AB - BACKGROUND: In older patients, evaluation of the cognitive status is crucial. The Mini-Mental State Examination (MMSE) is widely used for screening of cognition, providing fairly high sensitivity, specificity and reproducibility. Recently, a consensus emerged on the necessity of an international and transparent language, as provided by the WHO's International Classification of Functioning, Disability and Health (ICF). Most assessment tools however are not in accordance with the ICF. OBJECTIVE: To reformulate the MMSE according to the ICF, both for the individual items and for the scoring system. METHOD: MMSE data (scores varying from 3 to 30/30) of (1) 217 cognitively healthy elderly, (2) 60 persons with mild cognitive impairment, (3) 60 patients with mild Alzheimer's disease (AD), and (4) 60 patients with moderate/severe AD were obtained from studies at a university hospital setting. Subjects were aged 65 years or more and recruited either through advertisement (group 1), from the geriatric day hospital (groups 2 and 3), or the geriatric ward (group 4). The allocation to the groups was done after multidisciplinary evaluation. The conversion of the MMSE to ICF-MMSE was done by content comparison and by subsequent translation of the scoring system using automatic algorithms. RESULTS: All MMSE items were converted to the corresponding ICF categories. Three ICF domains were addressed: global and specific mental functions, general tasks and demands, divided over 6 ICF categories (orientation time/place, sustaining attention, memory functions, mental functions of language, undertaking a simple task). Scores on individual items were transformed according to their relative weight on the original MMSE scale, and a total ICF-MMSE score from 0 (no problem) to 100 (complete problem) was generated. Translation was satisfying, as illustrated by a good correlation between MMSE and ICF-MMSE. The diagnostic groups were distributed over the ICF-MMSE scores as expected. For each ICF domain, ICF-MMSE subscores were higher with increasing severity in cognitive decline. There was a higher dispersion, in accordance with the more detailed scoring possibilities of the ICF-MMSE. CONCLUSIONS: It is possible to adapt the MMSE to the ICF concept. This adaptation enhances interdisciplinary communication since it provides more clarity in assessment, with better visibility of the areas covered by the instrument. PMID- 22067432 TI - 'Relax and Repair' to restrain aging. AB - The maintenance of genomic integrity requires the precise identification and repair of DNA damage. Since DNA is packaged and condensed into higher order chromatin, the events associated with DNA damage recognition and repair are orchestrated within the layers of chromatin. Very similar to transcription, during DNA repair, chromatin remodelling events and histone modifications act in concert to 'open' and relax chromatin structure so that repair proteins can gain access to DNA damage sites. One such histone mark critical for maintaining chromatin structure is acetylated lysine 16 of histone H4 (AcH4K16), a modification that can disrupt higher order chromatin organization and convert it into a more 'relaxed' configuration. We have recently shown that impaired H4K16 acetylation delays the accumulation of repair proteins to double strand break (DSB) sites which results in defective genome maintenance and accelerated aging in a laminopathy-based premature aging mouse model. These results support the idea that epigenetic factors may directly contribute to genomic instability and aging by regulating the efficiency of DSB repair. In this article, the interplay between epigenetic misregulation, defective DNA repair and aging is discussed. PMID- 22067434 TI - An optimization of allocation of information granularity in the interpretation of data structures: toward granular fuzzy clustering. AB - Clustering forms one of the most visible conceptual and algorithmic framework of developing information granules. In spite of the algorithm being used, the representation of information granules-clusters is predominantly numeric (coming in the form of prototypes, partition matrices, dendrograms, etc.). In this paper, we consider a concept of granular prototypes that generalizes the numeric representation of the clusters and, in this way, helps capture more details about the data structure. By invoking the granulation-degranulation scheme, we design granular prototypes being reflective of the structure of data to a higher extent than the representation that is provided by their numeric counterparts (prototypes). The design is formulated as an optimization problem, which is guided by the coverage criterion, meaning that we maximize the number of data for which their granular realization includes the original data. The granularity of the prototypes themselves is treated as an important design asset; hence, its allocation to the individual prototypes is optimized so that the coverage criterion becomes maximized. With this regard, several schemes of optimal allocation of information granularity are investigated, where interval-valued prototypes are formed around the already produced numeric representatives. Experimental studies are provided in which the design of granular prototypes of interval format is discussed and characterized. PMID- 22067435 TI - A self-learning particle swarm optimizer for global optimization problems. AB - Particle swarm optimization (PSO) has been shown as an effective tool for solving global optimization problems. So far, most PSO algorithms use a single learning pattern for all particles, which means that all particles in a swarm use the same strategy. This monotonic learning pattern may cause the lack of intelligence for a particular particle, which makes it unable to deal with different complex situations. This paper presents a novel algorithm, called self-learning particle swarm optimizer (SLPSO), for global optimization problems. In SLPSO, each particle has a set of four strategies to cope with different situations in the search space. The cooperation of the four strategies is implemented by an adaptive learning framework at the individual level, which can enable a particle to choose the optimal strategy according to its own local fitness landscape. The experimental study on a set of 45 test functions and two real-world problems show that SLPSO has a superior performance in comparison with several other peer algorithms. PMID- 22067436 TI - Symbolic dynamic filtering and language measure for behavior identification of mobile robots. AB - This paper presents a procedure for behavior identification of mobile robots, which requires limited or no domain knowledge of the underlying process. While the features of robot behavior are extracted by symbolic dynamic filtering of the observed time series, the behavior patterns are classified based on language measure theory. The behavior identification procedure has been experimentally validated on a networked robotic test bed by comparison with commonly used tools, namely, principal component analysis for feature extraction and Bayesian risk analysis for pattern classification. PMID- 22067437 TI - Application of lignocellulolytic enzymes produced under solid state cultivation conditions. AB - In this paper, cellulose from brown-rot fungus Fomitopsis sp. RCK2010, thermostable and alkalostable xylanase from Bacillus pumilus MK001 and laccase from Ganoderma sp. rckk-02 were evaluated for (i) saccharification of alkali pretreated rice straw and wheat straw, (ii) upgradation of chick feed and (iii) decolorization of dyes, respectively. The cellulose from brown-rot fungus resulted in a sugar release of 151.48 and 214.11 mg/g, respectively, from rice straw and wheat straw, which was comparatively higher than the earlier reports. While xylan, one of the main anti-nutritional factors (ANFs) present in the chick feed was removed to an extent of 11.6 mg/g xylose sugars at 50 degrees C using the thermostable xylanase. Besides, the treatment with thermostable xylanase also brought about a release of 0.85 (mg/g) of soluble phosphorous. Moreover, the laccase when used for the decolorization of Remazol Brilliant Blue R (RBBR) and xylidine ponceau cause almost complete decolorization in 2 and 4h, respectively, depicting high rate of decolorization. PMID- 22067438 TI - Biosorption of food dyes onto Spirulina platensis nanoparticles: equilibrium isotherm and thermodynamic analysis. AB - The biosorption of food dyes FD&C red no. 40 and acid blue 9 onto Spirulina platensis nanoparticles was studied at different conditions of pH and temperature. Four isotherm models were used to evaluate the biosorption equilibrium and the thermodynamic parameters were estimated. Infra red analysis (FT-IR) and energy dispersive X-ray spectroscopy (EDS) were used to verify the biosorption behavior. The maximum biosorption capacities of FD&C red no. 40 and acid blue 9 were found at pH 4 and 298 K, and the values were 468.7 mg g(-1) and 1619.4 mg g(-1), respectively. The Sips model was more adequate to fit the equilibrium experimental data (R2>0.99 and ARE<5%). Thermodynamic study showed that the biosorption was exothermic, spontaneous and favorable. FT-IR and EDS analysis suggested that at pH 4 and 298 K, the biosorption of both dyes onto nanoparticles occurred by chemisorption. PMID- 22067439 TI - The anti-inflammatory effect of paraoxonase 1 against oxidized lipids depends on its association with high density lipoproteins. AB - AIM: The aims of this study were to investigate whether purified PON1 can reduce the pro-inflammatory effect of oxidized phospholipids and whether the effect depended on its association with HDL. MAIN METHODS: Lipid peroxidation was induced by copper ions and was measured using the conjugated diene method. Lysophosphatidylcholine (lyso-PC) formation was measured by HPLC with evaporative light scattering detection (ELSD) and ICAM-1 expression on Ea.hy926 endothelial cells was analyzed by flow cytometry. KEY FINDINGS: Purified PON1 significantly inhibited copper-induced oxidation of LDL and HDL, causing a 60.5% and 77.7% decrease in conjugated diene formation, respectively. Incubating PON1 with oxLDL caused a significant increase in lyso-PC levels, while oxHDL caused a significant decrease. PON1 (12.5 to 50 MUg/mL) had a pro-inflammatory effect in the presence of oxLDL, increasing ICAM-1 levels in Ea.hy926 cells by 33.0% and 40.6% (p<0.001) respectively, and had an anti-inflammatory effect in the presence of oxHDL, causing a 3-fold reduction in ICAM-1 levels. PON1 also caused a significant decrease in TNFalpha? and purified lyso-PC-induced ICAM-1 expression. The results obtained with reconstituted HDL as well as LCAT and PAF-AH inhibitors suggested that the anti-inflammatory effect of PON1 against oxidized lipids is dependent on its association with HDL. SIGNIFICANCE: Our results clearly showed that PON1 is involved in the anti-inflammatory effect of HDL and that the effect appears to depend on its association with HDL. PMID- 22067441 TI - Perceived stress and gastrointestinal symptoms in nursing students in Korea: A cross-sectional survey. AB - BACKGROUND: Although nursing students experience a high level of stress during their training, there has been limited research on stress and its impact on the student's physical responses, such as gastrointestinal symptoms. The aims of this study are to assess the prevalence of GI symptoms in nursing students in Korea and to examine the association between the perceived stress and GI symptoms. METHODS: A cross-sectional descriptive study design was used. A total of 715 students of a three-year associate degree nursing program in a Korean college participated. The Perceived Stress Scale and a GI Symptoms Questionnaire were administered through a self-reported system. Chi-square tests, Fisher's exact test, and logistic regression analysis were performed using SPSS 17.0. RESULTS: Sixty-five percent of the nursing students experienced more than one GI symptom, with 31.1% of students reporting more than three GI symptoms. Most of the nursing students complained of upper dysmotility and bowel symptoms. In addition, students who reported higher perceived stress were significantly more likely to complain of GI symptoms. Compared to nursing students with the lowest perceived stress level, the adjusted odds ratio (OR) for GI symptoms in students with the highest perceived stress level was 3.52 times higher (95% CI = 2.05-6.06). CONCLUSIONS: GI symptoms that are highly prevalent among nursing students are significantly associated with the perceived stress level. High perceived stress should be considered a risk factor for GI symptoms. To reduce perceived stress, stress management programs including cognitive reappraisal training are needed in nursing curriculum. PMID- 22067440 TI - Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. AB - This paper provides the first review of the memory-enhancing and neuroprotective metabolic mechanisms of action of methylene blue in vivo. These mechanisms have important implications as a new neurobiological approach to improve normal memory and to treat memory impairment and neurodegeneration associated with mitochondrial dysfunction. Methylene blue's action is unique because its neurobiological effects are not determined by regular drug-receptor interactions or drug-response paradigms. Methylene blue shows a hormetic dose-response, with opposite effects at low and high doses. At low doses, methylene blue is an electron cycler in the mitochondrial electron transport chain, with unparalleled antioxidant and cell respiration-enhancing properties that affect the function of the nervous system in a versatile manner. A major role of the respiratory enzyme cytochrome oxidase on the memory-enhancing effects of methylene blue is supported by available data. The memory-enhancing effects have been associated with improvement of memory consolidation in a network-specific and use-dependent fashion. In addition, low doses of methylene blue have also been used for neuroprotection against mitochondrial dysfunction in humans and experimental models of disease. The unique auto-oxidizing property of methylene blue and its pleiotropic effects on a number of tissue oxidases explain its potent neuroprotective effects at low doses. The evidence reviewed supports a mechanistic role of low-dose methylene blue as a promising and safe intervention for improving memory and for the treatment of acute and chronic conditions characterized by increased oxidative stress, neurodegeneration and memory impairment. PMID- 22067442 TI - Expression and imprinting analysis of the NESP55 gene in pigs. AB - Most imprinted genes play important roles in a mammalian development. One of them is GNAS complex locus which codes for several imprinted or biallelically expressed transcripts. The function of some of them are well understood (for example GSalpha-guanine nucleotide binding, alpha -stimulating protein is essential element of cell signaling), whereas the others are little known. The function of NESP55 (Neuroendocrine secretory protein 55) remains elusive, although there are suggestions about its role in brain development. Imprinted genes are currently being studied as potential candidate genes for quantitative trait loci (QTLs) in farm animals. In our study, we analyzed tissue distribution of NESP55 mRNA in pigs and established imprinting status of this gene in the brain stem, muscle, kidney and liver at several developmental stages. NESP55 mRNA was most abundant in central nervous system (CNS) and pituitary. Substantial expression was also noticed in the kidney, testis and muscle. Moreover, we identified a 12-nucleotides deletion within the coding region of NESP55 (accession number ss#342570450) which was used in imprinting analysis. The deletion was very rare in the analyzed populations and present only in heterozygous form. The imprinting analysis showed that NESP55 is maternally expressed in young and adult pigs, similar to what was obtained in humans, mice and cattle. PMID- 22067443 TI - PINA v2.0: mining interactome modules. AB - The Protein Interaction Network Analysis (PINA) platform is a comprehensive web resource, which includes a database of unified protein-protein interaction data integrated from six manually curated public databases, and a set of built-in tools for network construction, filtering, analysis and visualization. The second version of PINA enhances its utility for studies of protein interactions at a network level, by including multiple collections of interaction modules identified by different clustering approaches from the whole network of protein interactions ('interactome') for six model organisms. All identified modules are fully annotated by enriched Gene Ontology terms, KEGG pathways, Pfam domains and the chemical and genetic perturbations collection from MSigDB. Moreover, a new tool is provided for module enrichment analysis in addition to simple query function. The interactome data are also available on the web site for further bioinformatics analysis. PINA is freely accessible at http://cbg.garvan.unsw.edu.au/pina/. PMID- 22067444 TI - zfishbook: connecting you to a world of zebrafish revertible mutants. AB - zfishbook is an internet-based openly accessible database of revertible protein trap gene-breaking transposon (GBT) insertional mutants in the zebrafish, Danio rerio. In these lines, a monomeric red fluorescent protein (mRFP) is encoded by an artificial 3' exon, resulting in a translational fusion to endogenous loci. The natural transparency of the zebrafish embryo and larvae greatly facilitates the expression annotation of tagged loci using new capillary-based SCORE imaging methods. Molecular annotation of each line is facilitated by cloning methods such as 5'-Rapid Amplification of cDNA Ends (RACE) and inverse polymerase chain reaction (PCR). zfishbook (http://zfishbook.org) represents a central hub for molecular, expression and mutational information about GBT lines from the International Zebrafish Protein Trap Consortium (IZPTC) that includes researchers from around the globe. zfishbook is open to community-wide contributions including expression and functional annotation. zfishbook also represents a central location for information on how to obtain these lines from diverse members of the IZPTC and integration within other zebrafish community databases including Zebrafish Information Network (ZFIN), Ensembl and National Center for Biotechnology Information. PMID- 22067445 TI - SCRIPDB: a portal for easy access to syntheses, chemicals and reactions in patents. AB - The patent literature is a rich catalog of biologically relevant chemicals; many public and commercial molecular databases contain the structures disclosed in patent claims. However, patents are an equally rich source of metadata about bioactive molecules, including mechanism of action, disease class, homologous experimental series, structural alternatives, or the synthetic pathways used to produce molecules of interest. Unfortunately, this metadata is discarded when chemical structures are deposited separately in databases. SCRIPDB is a chemical structure database designed to make this metadata accessible. SCRIPDB provides the full original patent text, reactions and relationships described within any individual patent, in addition to the molecular files common to structural databases. We discuss how such information is valuable in medical text mining, chemical image analysis, reaction extraction and in silico pharmaceutical lead optimization. SCRIPDB may be searched by exact chemical structure, substructure or molecular similarity and the results may be restricted to patents describing synthetic routes. SCRIPDB is available at http://dcv.uhnres.utoronto.ca/SCRIPDB. PMID- 22067446 TI - Specialization of an Exonuclease III family enzyme in the repair of 3' DNA lesions during base excision repair in the human pathogen Neisseria meningitidis. AB - We have previously demonstrated that the two Exonuclease III (Xth) family members present within the obligate human pathogen Neisseria meningitidis, NApe and NExo, are important for survival under conditions of oxidative stress. Of these, only NApe possesses AP endonuclease activity, while the primary function of NExo remained unclear. We now reveal further functional specialization at the level of 3'-PO(4) processing for NExo. We demonstrate that the bi-functional meningococcal glycosylases Nth and MutM can perform strand incisions at abasic sites in addition to NApe. However, no such functional redundancy exists for the 3' phosphatase activity of NExo, and the cytotoxicity of 3'-blocking lesions is reflected in the marked sensitivity of a mutant lacking NExo to oxidative stress, compared to strains deficient in other base excision repair enzymes. A histidine residue within NExo that is responsible for its lack of AP endonuclease activity is also important for its 3'-phosphatase activity, demonstrating an evolutionary trade off in enzyme function at the single amino acid level. This specialization of two Xth enzymes for the 3'-end processing and strand-incision reactions has not previously been observed and provides a new paradigm within the prokaryotic world for separation of these critical functions during base excision repair. PMID- 22067447 TI - Ensembl Genomes: an integrative resource for genome-scale data from non vertebrate species. AB - Ensembl Genomes (http://www.ensemblgenomes.org) is an integrative resource for genome-scale data from non-vertebrate species. The project exploits and extends technology (for genome annotation, analysis and dissemination) developed in the context of the (vertebrate-focused) Ensembl project and provides a complementary set of resources for non-vertebrate species through a consistent set of programmatic and interactive interfaces. These provide access to data including reference sequence, gene models, transcriptional data, polymorphisms and comparative analysis. Since its launch in 2009, Ensembl Genomes has undergone rapid expansion, with the goal of providing coverage of all major experimental organisms, and additionally including taxonomic reference points to provide the evolutionary context in which genes can be understood. Against the backdrop of a continuing increase in genome sequencing activities in all parts of the tree of life, we seek to work, wherever possible, with the communities actively generating and using data, and are participants in a growing range of collaborations involved in the annotation and analysis of genomes. PMID- 22067448 TI - VFDB 2012 update: toward the genetic diversity and molecular evolution of bacterial virulence factors. AB - The virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) has served as a comprehensive repository of bacterial virulence factors (VFs) for >7 years. Bacterial virulence is an exciting and dynamic field, due to the availability of complete sequences of bacterial genomes and increasing sophisticated technologies for manipulating bacteria and bacterial genomes. The intricacy of virulence mechanisms offers a challenge, and there exists a clear need to decipher the 'language' used by VFs more effectively. In this article, we present the recent major updates of VFDB in an attempt to summarize some of the most important virulence mechanisms by comparing different compositions and organizations of VFs from various bacterial pathogens, identifying core components and phylogenetic clades and shedding new light on the forces that shape the evolutionary history of bacterial pathogenesis. In addition, the 2012 release of VFDB provides an improved user interface. PMID- 22067450 TI - Permanent or reversible conjugation of 2'-O- or 5'-O-aminooxymethylated nucleosides with functional groups as a convenient and efficient approach to the modification of RNA and DNA sequences. AB - 2'-O-Aminooxymethyl ribonucleosides are prepared from their 3',5'-disilylated 2' O-phthalimidooxymethyl derivatives by treatment with NH(4)F in MeOH. The reaction of these novel ribonucleosides with 1-pyrenecarboxaldehyde results in the efficient formation of stable and yet reversible ribonucleoside 2'-conjugates in yields of 69-82%. Indeed, exposure of these conjugates to 0.5 M tetra-n butylammonium fluoride (TBAF) in THF results in the cleavage of their iminoether functions to give the native ribonucleosides along with the innocuous nitrile side product. Conversely, the reaction of 5-cholesten-3-one or dansyl chloride with 2'-O-aminooxymethyl uridine provides permanent uridine 2'-conjugates, which are left essentially intact upon treatment with TBAF. Alternatively, 5'-O aminooxymethyl thymidine is prepared by hydrazinolysis of its 3'-O-levulinyl-5'-O phthalimidooxymethyl precursor. Pyrenylation of 5'-O-aminooxymethyl thymidine and the sensitivity of the 5'-conjugate to TBAF further exemplify the usefulness of this nucleoside for modifying DNA sequences either permanently or reversibly. Although the versatility and uniqueness of 2'-O-aminooxymethyl ribonucleosides in the preparation of modified RNA sequences is demonstrated by the single or double incorporation of a reversible pyrenylated uridine 2'-conjugate into an RNA sequence, the conjugation of 2'-O-aminooxymethyl ribonucleosides with aldehydes, including those generated from their acetals, provides reversible 2'-O-protected ribonucleosides for potential applications in the solid-phase synthesis of native RNA sequences. The synthesis of a chimeric polyuridylic acid is presented as an exemplary model. PMID- 22067449 TI - LSD1 cooperates with CTIP2 to promote HIV-1 transcriptional silencing. AB - Microglial cells are the main HIV-1 targets in the central nervous system (CNS) and constitute an important reservoir of latently infected cells. Establishment and persistence of these reservoirs rely on the chromatin structure of the integrated proviruses. We have previously demonstrated that the cellular cofactor CTIP2 forces heterochromatin formation and HIV-1 gene silencing by recruiting HDAC and HMT activities at the integrated viral promoter. In the present work, we report that the histone demethylase LSD1 represses HIV-1 transcription and viral expression in a synergistic manner with CTIP2. We show that recruitment of LSD1 at the HIV-1 proximal promoter is associated with both H3K4me3 and H3K9me3 epigenetic marks. Finally, our data suggest that LSD1-induced H3K4 trimethylation is linked to hSET1 recruitment at the integrated provirus. PMID- 22067451 TI - IDEAL: Intrinsically Disordered proteins with Extensive Annotations and Literature. AB - IDEAL, Intrinsically Disordered proteins with Extensive Annotations and Literature (http://www.ideal.force.cs.is.nagoya-u.ac.jp/IDEAL/), is a collection of knowledge on experimentally verified intrinsically disordered proteins. IDEAL contains manual annotations by curators on intrinsically disordered regions, interaction regions to other molecules, post-translational modification sites, references and structural domain assignments. In particular, IDEAL explicitly describes protean segments that can be transformed from a disordered state to an ordered state. Since in most cases they can act as molecular recognition elements upon binding of partner proteins, IDEAL provides a data resource for functional regions of intrinsically disordered proteins. The information in IDEAL is provided on a user-friendly graphical view and in a computer-friendly XML format. PMID- 22067452 TI - WormBase 2012: more genomes, more data, new website. AB - Since its release in 2000, WormBase (http://www.wormbase.org) has grown from a small resource focusing on a single species and serving a dedicated research community, to one now spanning 15 species essential to the broader biomedical and agricultural research fields. To enhance the rate of curation, we have automated the identification of key data in the scientific literature and use similar methodology for data extraction. To ease access to the data, we are collaborating with journals to link entities in research publications to their report pages at WormBase. To facilitate discovery, we have added new views of the data, integrated large-scale datasets and expanded descriptions of models for human disease. Finally, we have introduced a dramatic overhaul of the WormBase website for public beta testing. Designed to balance complexity and usability, the new site is species-agnostic, highly customizable, and interactive. Casual users and developers alike will be able to leverage the public RESTful application programming interface (API) to generate custom data mining solutions and extensions to the site. We report on the growth of our database and on our work in keeping pace with the growing demand for data, efforts to anticipate the requirements of users and new collaborations with the larger science community. PMID- 22067453 TI - A flexible brace maintains the assembly of a hexameric replicative helicase during DNA unwinding. AB - The mechanism of DNA translocation by papillomavirus E1 and polyomavirus LTag hexameric helicases involves consecutive remodelling of subunit-subunit interactions around the hexameric ring. Our biochemical analysis of E1 helicase demonstrates that a 26-residue C-terminal segment is critical for maintaining the hexameric assembly. As this segment was not resolved in previous crystallographic analysis of E1 and LTag hexameric helicases, we determined the solution structure of the intact hexameric E1 helicase by Small Angle X-ray Scattering. We find that the C-terminal segment is flexible and occupies a cleft between adjacent subunits in the ring. Electrostatic potential calculations indicate that the negatively charged C-terminus can bridge the positive electrostatic potentials of adjacent subunits. Our observations support a model in which the C-terminal peptide serves as a flexible 'brace' maintaining the oligomeric state during conformational changes associated with ATP hydrolysis. We argue that these interactions impart processivity to DNA unwinding. Sequence and disorder analysis suggest that this mechanism of hexamer stabilization would be conserved among papillomavirus E1 and polyomavirus LTag hexameric helicases. PMID- 22067454 TI - A role for insulator elements in the regulation of gene expression response to hypoxia. AB - Hypoxia inducible factor (HIF) up-regulates the transcription of a few hundred genes required for the adaptation to hypoxia. This restricted set of targets is in sharp contrast with the widespread distribution of the HIF binding motif throughout the genome. Here, we investigated the transcriptional response of GYS1 and RUVBL2 genes to hypoxia to understand the mechanisms that restrict HIF activity toward specific genes. GYS1 and RUVBL2 genes are encoded by opposite DNA strands and separated by a short intergenic region (~1 kb) that contains a functional hypoxia response element equidistant to both genes. However, hypoxia induced the expression of GYS1 gene only. Analysis of the transcriptional response of chimeric constructs derived from the intergenic region revealed an inhibitory sequence whose deletion allowed RUVBL2 induction by HIF. Enhancer blocking assays, performed in cell culture and transgenic zebrafish, confirmed the existence of an insulator element within this inhibitory region that could explain the differential regulation of GYS1 and RUVBL2 by hypoxia. Hence, in this model, the selective response to HIF is achieved with the aid of insulator elements. This is the first report suggesting a role for insulators in the regulation of differential gene expression in response to environmental signals. PMID- 22067455 TI - SuperTarget goes quantitative: update on drug-target interactions. AB - There are at least two good reasons for the on-going interest in drug-target interactions: first, drug-effects can only be fully understood by considering a complex network of interactions to multiple targets (so-called off-target effects) including metabolic and signaling pathways; second, it is crucial to consider drug-target-pathway relations for the identification of novel targets for drug development. To address this on-going need, we have developed a web based data warehouse named SuperTarget, which integrates drug-related information associated with medical indications, adverse drug effects, drug metabolism, pathways and Gene Ontology (GO) terms for target proteins. At present, the updated database contains >6000 target proteins, which are annotated with >330,000 relations to 196,000 compounds (including approved drugs); the vast majority of interactions include binding affinities and pointers to the respective literature sources. The user interface provides tools for drug screening and target similarity inclusion. A query interface enables the user to pose complex queries, for example, to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target proteins within a certain affinity range. SuperTarget is available at http://bioinformatics.charite.de/supertarget. PMID- 22067456 TI - FlyRNAi.org--the database of the Drosophila RNAi screening center: 2012 update. AB - FlyRNAi (http://www.flyrnai.org), the database and website of the Drosophila RNAi Screening Center (DRSC) at Harvard Medical School, serves a dual role, tracking both production of reagents for RNA interference (RNAi) screening in Drosophila cells and RNAi screen results. The database and website is used as a platform for community availability of protocols, tools, and other resources useful to researchers planning, conducting, analyzing or interpreting the results of Drosophila RNAi screens. Based on our own experience and user feedback, we have made several changes. Specifically, we have restructured the database to accommodate new types of reagents; added information about new RNAi libraries and other reagents; updated the user interface and website; and added new tools of use to the Drosophila community and others. Overall, the result is a more useful, flexible and comprehensive website and database. PMID- 22067457 TI - Management of seasonal allergic conjunctivitis: guide to therapy. AB - Seasonal allergic conjunctivitis (SAC) is an inflammatory response of the conjunctiva triggered by exposure to seasonal allergens. Treatment options for SAC include artificial tears, antihistamines, decongestants, mast cell stabilizers, nonsteroidal anti-inflammatory drugs, dual antihistamine/mast cell stabilizers, immunotherapy and corticosteroids. Topical, intranasal and systemic formulations of corticosteroids have traditionally provided the most effective relief of the inflammation and signs and symptoms associated with severe, acute exacerbations of SAC. However, steroid-induced ocular and systemic side-effects have limited the prescribing of these agents. This limitation of traditional corticosteroids led to the development of modified corticosteroids that retain the anti-inflammatory mechanism of action of traditional corticosteroids with a much-improved safety profile because of their rapid breakdown to inactive metabolites after exerting their activity. The development of one such novel corticosteroid, loteprednol etabonate (LE), led to the insertion of an ester (instead of a ketone) group at the carbon-20 (C-20) position of the basic corticosteroid structure. Clinical trials assessing this C-20 ester corticosteroid have demonstrated similar efficacy to C-20 ketone corticosteroids in the prevention or treatment of the signs and symptoms of SAC but with a greatly improved safety profile, as the C-20 ester corticosteroid is less likely to elevate intraocular pressure. In addition, the ketone at the C-20 position has been implicated in the formation of cataract, while nonketolic corticosteroids do not form Schiff base intermediates with lens proteins, which is a common first step in cataractogenesis. The clinical relevance of the C-20 ester corticosteroid class, as modelled by LE, is that they provide both effective and safe treatment of the inflammation associated with SAC and relief of its signs and symptoms. Loteprednol etabonate offers a well-tolerated treatment option for patients with debilitating acute exacerbations as well as chronic forms of the disease. PMID- 22067458 TI - Setting the clock for recirculating lymphocytes. AB - In their search for antigens, lymphocytes continuously shuttle among blood vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization, a process that decreases their signaling output after previous exposure to high ligand concentration. Such desensitization can explain why lymphocytes do not take an intermediate position between two signals but rather oscillate between them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase 2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high vascular S1P concentrations, thereby reducing responsiveness to the chemokine signal and trapping the cells in the vascular compartment. The desensitization kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature and lymphatic tissue, although the positional information in both compartments is static. PMID- 22067459 TI - Short RNA duplexes elicit RIG-I-mediated apoptosis in a cell type- and length dependent manner. AB - Short double-stranded RNAs (dsRNAs) induce type I interferon (IFN)-mediated innate immune responses. In functional studies with short interfering RNAs or synthetic mimics of microRNA precursors in vitro, we found that short dsRNAs readily induced apoptosis in cells derived from human granulosa cell tumors, but not in other cell types. Apoptosis was independent of the sequence of the dsRNA, but depended on its length, and was induced by 23- and 24-nucleotide (nt) dsRNAs, but not by shorter dsRNAs (< 22 nt) or by the long dsRNA polyinosinic polycytidylic acid. Microarray analysis revealed that apoptosis was accompanied by the increased expression of IFN-stimulated genes; however, several lines of evidence showed that IFNs did not directly induce apoptosis. Subsequent analyses revealed that the short dsRNAs increased the expression of retinoic acid inducible gene I (RIG-I) through dsRNA-activated protein kinase (PKR). Although these dsRNAs bore 3' overhangs and nontriphosphate 5' termini, which are not thought to be RIG-I-activating structures, the dsRNAs bound to RIG-I and triggered proapoptotic signaling mostly by activating RIG-I, which was followed by activation of the mitogen-activated protein kinase p38. Thus, we suggest that ligand recognition and subsequent signaling by RNA sensors are more complicated than previously believed. In addition, short dsRNAs may serve as pharmacological agents to target specific tumors, such as granulosa cell tumors. PMID- 22067462 TI - Promoting services. PMID- 22067461 TI - Differential hemodynamic effects of levosimendan in a porcine model of neonatal hypoxia-reoxygenation. AB - BACKGROUND: Neonatal asphyxia can be complicated by myocardial dysfunction with secondary alterations in pulmonary and regional hemodynamics. Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates. METHODS: Mixed breed piglets (1-4 days old, weight 1.6-2.3 kg) were acutely instrumented. Normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h, followed by reoxygenation with 100% (1 h) and then 21% oxygen (3 h). At 2 h of reoxygenation, after volume loading (Ringer's lactate 10 ml/kg), either levosimendan (0.1 or 0.2 MUg/kg/min) or D(5)W (placebo) was infused for 2 h in a blinded, block-randomized fashion (n = 7-8/group). The systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics were compared. RESULTS: At 0.1 and 0.2 MUg/kg/min, levosimendan significantly increased cardiac output (121 and 123% of pretreatment, respectively) and heart rate, and decreased systemic vascular resistance without causing hypotension. Pulmonary arterial pressure and estimated pulmonary vascular resistance were significantly increased from pretreatment baseline in 0.1 but not 0.2 MUg/kg/min levosimendan. Levosimendan infusion had no effects on regional hemodynamics. Myocardial efficiency but not oxygen consumption increased with 0.1 MUg/kg/min levosimendan without significant effects on plasma troponin and myocardial lactate levels. CONCLUSIONS: In newborn piglets following hypoxia-reoxygenation injury, levosimendan improves cardiac output but has no marked effects in carotid, superior mesenteric and renal perfusion. It appears that various doses of levosimendan increase the cardiac output through different mechanisms. Further investigations are needed to examine the effectiveness of levosimendan as a cardiovascular supportive therapy either alone or in conjunction with other inotropes in asphyxiated neonates. PMID- 22067460 TI - Systematic phosphorylation analysis of human mitotic protein complexes. AB - Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. Most, if not all, of the mitotic processes are regulated by a set of mitotic protein kinases that control protein activity by phosphorylation. Although many mitotic phosphorylation events have been identified in proteome-scale mass spectrometry studies, information on how these phosphorylation sites are distributed within mitotic protein complexes and which kinases generate these phosphorylation sites is largely lacking. We used systematic protein-affinity purification combined with mass spectrometry to identify 1818 phosphorylation sites in more than 100 mitotic protein complexes. In many complexes, the phosphorylation sites were concentrated on a few subunits, suggesting that these subunits serve as "switchboards" to relay the kinase regulatory signals within the complexes. Consequent bioinformatic analyses identified potential kinase-substrate relationships for most of these sites. In a subsequent in-depth analysis of key mitotic regulatory complexes with the Aurora kinase B (AURKB) inhibitor Hesperadin and a new Polo-like kinase (PLK1) inhibitor, BI 4834, we determined the kinase dependency for 172 phosphorylation sites on 41 proteins. Combination of the results of the cellular studies with Scansite motif prediction enabled us to identify 14 sites on six proteins as direct candidate substrates of AURKB or PLK1. PMID- 22067463 TI - Skin care in the older person: a focus on the use of emollients. AB - This article gives an overview of pathophysiological changes in the older person's skin, with particular focus on dry skin and the important use of emollient therapy. This includes guidance on emollient choice, function and application. Education is emphasized as an important factor in patient/carer concordance, with additional advice also recommended to extend education to other health care professionals in terms of correct usage and prescription amounts. Best practice of the use of emollient therapy is the main objective of this article, promoting the health professional to place skin care assessment high on the patient need agenda, and to recognize this therapy as the first-line treatment in all dry skin management. PMID- 22067464 TI - Providing information and advice on diet to stoma patients. AB - The community nurse will encounter many queries and requests for advice in the work environment. This article offers information on diet related to the stoma. Specific advice for the three different types of stoma, and for certain situations that might arise after the ostomate (person with a stoma) is discharged home, is provided. Much of the advice is common sense, but it might prevent the use of medication such as laxatives. Nutrition is essential for recovery following surgery and in the long-term. By using the information provided, the community nurse can give better care to this group of patients. PMID- 22067465 TI - Assessment and management of diabetic foot ulcers. AB - Diabetic foot ulcers can cause considerable disability and morbidity. The complex pathology requires expert and in-depth assessment and management to achieve the best outcomes. Assessment is underpinned by attention to four key points: vascular sufficiency, neurological/sensory status, appropriateness of footwear, and presence of foot deformity. The 'shopping list' for management is derived from the assessment and requires careful planning and a multidisciplinary approach. This article outlines key first line principles and practices in assessment and management of diabetic foot ulcers, including the importance of offloading pressure and mechanical trauma to aid healing and prevent recurrence. PMID- 22067466 TI - Skin changes at life's end: SCALE ulcer or pressure ulcer? AB - Pressure ulceration causes much distress to patients and family, and can be taken as an indication of poor nursing care. It is vital that both parties understand when pressure damage can be prevented, and those circumstances when skin failure at the end of life cannot be avoided. Appropriate risk assessment, provision of all appropriate care, and use of pressure relieving equipment to minimize the risk of any loss of skin integrity are required. The recognition of Skin Changes at Life's End (SCALE) ulcers may herald the imminent demise of a loved one. Families require support and good communication from nursing staff at this difficult time. PMID- 22067467 TI - Meeting the policy agenda, part 1: the role of the modern district nurse. AB - The challenges posed by the current context of health and social care offer opportunities for different models of care delivery. District nursing has evolved, and continues to evolve to meet these challenges. The traditional reactive role of district nursing has developed as contemporary practice expects district nurses to meet both planned and unplanned care required by practice populations. Modern anticipatory care approaches to care are being adopted, while care and case management is being facilitated and delivered to patients and families with complex health and social care needs. Additionally, district nurses are recognizing the need to further develop management and leadership skills as the teams delivering care consist of a skill mix of nurses and other disciplines. They are also charged with evidencing the impact of what they do and influencing care delivery at every level of healthcare organizations. This first paper of two will explore the current UK policy context and ways in which district nursing services within each country are changing to meet the challenges posed. A second article will argue the need to ensure the district nursing workforce is underpinned by robust educational standards that ensure protection of the public. The influences of education and development from professional and organizational perspectives will be examined. PMID- 22067468 TI - Self-management for young people with mental health conditions. PMID- 22067469 TI - Social media and health care: an interactive future. PMID- 22067470 TI - Looking at the extent of fraud within the NHS. AB - Fraud costs the NHS billions of pounds each year, and takes money away from frontline services. The Fraud Act 2006 has made the offence clearer and therefore easier to bring prosecutions. Offences can range from false representation about qualifications and experience to fraudulent consent forms, and through to bogus invoices and charging ghost patients. In this article, Richard Griffith and Cassam Tengnah outline what constitutes fraud and the measures taken by the NHS to counter fraudulent activity. PMID- 22067471 TI - Learning from others. PMID- 22067472 TI - The expanding relevance of nuclear mTOR in carcinogenesis. AB - Deregulated mTOR signaling drives the growth of various human cancers, making mTOR a major target for development of cancer chemotherapeutics. The role of mTOR in carcinogenesis is thought to be largely a consequence of its activity in the cytoplasm resulting in increased translation of pro-tumorigenic genes. However, emerging data locate mTOR in various subcellular compartments including Golgi, mitochondria, endoplasmic reticulum, and the nucleus, implying the presence of compartment-specific mTOR substrates and functions. Efforts to identify mTOR substrates in these compartments, and the mechanisms by which mTOR recruits these substrates and affects downstream cellular processes, will add to our understanding of the diversity of roles played by mTOR in carcinogenesis. PMID- 22067474 TI - Medical evacuation of patients to other hospitals due to the Fukushima I nuclear accidents. PMID- 22067473 TI - Dedicated outreach service for hard to reach patients with tuberculosis in London: observational study and economic evaluation. AB - OBJECTIVE: To assess the cost effectiveness of the Find and Treat service for diagnosing and managing hard to reach individuals with active tuberculosis. DESIGN: Economic evaluation using a discrete, multiple age cohort, compartmental model of treated and untreated cases of active tuberculosis. SETTING: London, United Kingdom. Population Hard to reach individuals with active pulmonary tuberculosis screened or managed by the Find and Treat service (48 mobile screening unit cases, 188 cases referred for case management support, and 180 cases referred for loss to follow-up), and 252 passively presenting controls from London's enhanced tuberculosis surveillance system. MAIN OUTCOME MEASURES: Incremental costs, quality adjusted life years (QALYs), and cost effectiveness ratios for the Find and Treat service. RESULTS: The model estimated that, on average, the Find and Treat service identifies 16 and manages 123 active cases of tuberculosis each year in hard to reach groups in London. The service has a net cost of L1.4 million/year and, under conservative assumptions, gains 220 QALYs. The incremental cost effectiveness ratio was L6400-L10,000/QALY gained (about ?7300-?11,000 or $10,000-$16 000 in September 2011). The two Find and Treat components were also cost effective, even in unfavourable scenarios (mobile screening unit (for undiagnosed cases), L18,000-L26,000/QALY gained; case management support team, L4100-L6800/QALY gained). CONCLUSIONS: Both the screening and case management components of the Find and Treat service are likely to be cost effective in London. The cost effectiveness of the mobile screening unit in particular could be even greater than estimated, in view of the secondary effects of infection transmission and development of antibiotic resistance. PMID- 22067475 TI - Welfare, temperance and compulsory commitment to care for persons with substance misuse problems: a comparative study of 38 European countries. AB - AIMS: The study explores the existence and types of law on compulsory commitment to care (CCC) of adult substance misusers in Europe and how such laws are related to variations in demographics, alcohol consumption and epidemiology in misuse of opiates, cocaine, amphetamines, temperance culture heritage, health and welfare expenditure, and involvement and role of the state in welfare distribution. MATERIAL AND METHODS: Legal information on laws on CCC of misusers was obtained primarily through a survey of 38 European countries. Predictors of laws on CCC, and types of such, were analyzed from country descriptors in multivariate models. RESULTS: A majority (74%) of the explored countries have a law concerning CCC. The most common type of CCC law is within criminal justice legislation (45%), but civil CCC is almost as frequent (37%). These two models of CCC legislation are related to differences in cultural heritage and welfare distribution models. CONCLUSIONS: Temperance cultures, i.e. countries with a history of a strong temperance movement, and countries with a Beveridgean distribution of welfare, i.e. through the state, tend to favor civil CCC, while countries with a Bismarckian distribution of welfare, i.e. through insurance with less state interference, tend to favor CCC within criminal justice legislation. PMID- 22067476 TI - Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction (EXAMI): study protocol for a randomized controlled trial. AB - BACKGROUND: Myocardial infarction causes irreversible loss of cardiomyocytes and may lead to loss of ventricular function, morbidity and mortality. Infarct size is a major prognostic factor and reduction of infarct size has therefore been an important objective of strategies to improve outcomes. In experimental studies, glucagon-like peptide 1 and exenatide, a long acting glucagon-like peptide 1 receptor agonist, a novel drug introduced for the treatment of type 2 diabetes, reduced infarct size after myocardial infarction by activating pro-survival pathways and by increasing metabolic efficiency. METHODS: The EXAMI trial is a multi-center, prospective, randomized, placebo controlled trial, designed to evaluate clinical outcome of exenatide infusion on top of standard treatment, in patients with an acute myocardial infarction, successfully treated with primary percutaneous coronary intervention. A total of 108 patients will be randomized to exenatide (5 MUg bolus in 30 minutes followed by continuous infusion of 20 MUg/24 h for 72 h) or placebo treatment. The primary end point of the study is myocardial infarct size (measured using magnetic resonance imaging with delayed enhancement at 4 months) as a percentage of the area at risk (measured using T2 weighted images at 3-7 days). DISCUSSION: If the current study demonstrates cardioprotective effects, exenatide may constitute a novel therapeutic option to reduce infarct size and preserve cardiac function in adjunction to reperfusion therapy in patients with acute myocardial infarction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01254123. PMID- 22067477 TI - Identification, phylogenetic analysis and expression profile of an anionic insect defensin gene, with antibacterial activity, from bacterial-challenged cotton leafworm, Spodoptera littoralis. AB - BACKGROUND: Defensins are a well known family of cationic antibacterial peptides (AMPs) isolated from fungi, plants, insects, mussels, birds, and various mammals. They are predominantly active against gram (+) bacteria, and a few of them are also active against gram (-) bacteria and fungi. All insect defensins belonging to the invertebrate class have a consensus motif, C-X5-16-C-X3-C-X9-10-C-X4-7-CX1 C. Only seven AMPs have already been found in different lepidopteran species. No report was published on the isolation of defensin from the Egyptian cotton leafworm, Spodoptera littoralis. RESULTS: An anionic defensin, termed SpliDef, was isolated from the haemolymph of the cotton leafworm, S. littoralis, after bacterial challenge using differential display technique. Based on sequence analyses of the data, specific primers for full length and mature peptide of defensin were designed and successfully amplified 471 and 150 bp amplicons. The integration of the results revealed that the 471 bp-PCR product has one open reading frame (orf) of 303 bp long, including both start codon (AUG) and stop codon (UGA). The deduced peptide consists of a 23-residues signal peptide, a 27 residues propeptide and a 50-residues mature peptide with the conserved six cysteine motif of insect defensins. Both haemolymph and expressed protein exhibited antibacterial activities comparable to positive control. The RT-qPCR indicated that it was more than 41-folds up-regulated at 48 h p.i. CONCLUSION: Our results highlight an important immune role of the defensin gene in Spodoptera littoralis by cooperating with other AMPs to control bacterial infection. PMID- 22067478 TI - Risk of schizophrenia in relation to parental origin and genome-wide divergence. AB - BACKGROUND: Second-generation immigrants have an increased risk of schizophrenia, a finding that still lacks a satisfactory explanation. Various operational definitions of second-generation immigrants have been used, including foreign parental country of birth. However, with increasing global migration, it is not clear that parental country of birth necessarily is informative with regard to ethnicity. We compare two independently collected measures of parental foreign ethnicity, parental foreign country of birth versus genetic divergence, based on genome-wide genotypic data, to access which measure most efficiently captures the increased risk of schizophrenia among second-generation immigrants residing in Denmark. METHOD: A case-control study covering all children born in Denmark since 1981 included 892 cases of schizophrenia and 883 matched controls. Genetic divergence was assessed using principal component analyses of the genotypic data. Independently, parental foreign country of birth was assessed using information recorded prospectively in the Danish Civil Registration System. We compared incidence rate ratios of schizophrenia associated with these two independently collected measures of parental foreign ethnicity. RESULTS: People with foreign born parents had a significantly increased risk of schizophrenia [relative risk (RR) 1.94 (95% confidence intervals (CI) 1.41-2.65)]. Genetically divergent persons also had a significant increased risk [RR 2.43 (95% CI 1.55-3.82)]. Mutual adjustment of parental foreign country of birth and genetic divergence showed no difference between these measures with regard to their potential impact on the results. CONCLUSIONS: In terms of RR of schizophrenia, genetic divergence and parental foreign country of birth are interchangeable entities, and both entities have validity with regard to identifying second-generation immigrants. PMID- 22067479 TI - Intrathecal lemnalol, a natural marine compound obtained from Formosan soft coral, attenuates nociceptive responses and the activity of spinal glial cells in neuropathic rats. AB - The investigators previously found that the administration of lemnalol, a natural marine compound isolated from the Formosan soft coral Lemnalia cervicorni, produced anti-inflammatory and analgesic effects in carrageenan-injected rats. Recently, several studies have demonstrated that the development and maintenance of neuropathic pain are accompanied by releasing of proinflammatory mediators from activated glial cells in the spinal cord. In this study, we investigated the antinociceptive properties of lemnalol, a potential anti-inflammatory compound, on chronic constriction injury (CCI) in a well-established rat model of neuropathic pain. Our results demonstrated that a single intrathecal administration of lemnalol (0.05-10 MUg) significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia, 14 days postsurgery. Furthermore, immunohistofluorescence analyses showed that lemnalol (10 MUg) also significantly inhibits CCI-induced upregulation of microglial and astrocytic immunohistochemical activation markers in the dorsal horn of the lumbar spinal cord. Double immunofluorescent staining demonstrated that intrathecal injection of lemnalol (10 MUg) markedly inhibited spinal proinflammatory mediator tumor necrosis factor-alpha expression in microglial cells and astrocytes in neuropathic rats. Collectively, our results indicate that lemnalol is a potential therapeutic agent for neuropathic pain, and that further exploration of the effects of lemnalol on glial proinflammatory responses is warranted. PMID- 22067480 TI - Learning impairment by Delta(9)-tetrahydrocannabinol in adolescence is attributable to deficits in chunking. AB - Cannabis is the most popular illicit drug used by adolescents. Yet, there are only a few studies that have examined the effects of cannabis use on learning and memory during this sensitive and important neurodevelopmental stage. Male adolescent Sprague-Dawley rats were treated with Delta(9)-tetrahydrocannabinol (THC, 6 mg/kg) daily for 27 days and concurrently trained in a spatial learning and memory task. The chronic effects of cannabis use were specifically examined by assessing animal behaviour during the 'postacute' period (17 h after drug exposure), when minimal acute drug burden is expected to be present. The postacute period is a good model for cannabis use patterns in human adolescents. In addition, we investigated whether the hierarchical organization of working memory (chunking) was impaired by THC-treatment. We show that THC exposure impairs adolescent learning when tested in the postacute period, and that THC impairs the ability of animals to use a chunking strategy. PMID- 22067481 TI - Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity. AB - Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. In advanced AMD, new vessels from choriocapillaris (CC) invade through the Bruch's membrane (BrM) into the retina, forming choroidal neovascularization (CNV). BrM, an elastic lamina that is located between the retinal pigment epithelium (RPE) and CC, is thought to act as a physical and functional barrier against CNV. The BrM of patients with early AMD are characterized by decreased levels of antiangiogenic factors, including endostatin, thrombospondin-1 (TSP-1), and pigment epithelium-derived factor (PEDF), as well as by degeneration of the elastic layer. Motivated by a previous report that heat increases elastin expression in human skin, we examined the effect of heat on human ARPE-19 cell production of BrM components. Heat treatment stimulated the production of BrM components, including TSP-1, PEDF, and tropoelastin in vitro and increased the antiangiogenic activity of RPE measured in a mouse corneal pocket assay. The effect of heat on experimental CNV was investigated by pretreating the retina with heat via infrared diode laser prior to the induction of CNV. Heat treatment blocked the development of experimental CNV in vivo. These findings suggest that heat treatment may restore BrM integrity and barrier function against new vessel growth. PMID- 22067482 TI - HIF-1alpha coordinates lymphangiogenesis during wound healing and in response to inflammation. AB - This study aimed to investigate the mechanisms that coordinate lymphangiogenesis. Using mouse models of lymphatic regeneration and inflammatory lymphangiogenesis, we explored the hypothesis that hypoxia inducible factor-alpha (HIF-1alpha) is a central regulator of lymphangiogenesis. We show that HIF-1alpha inhibition by small molecule inhibitors (YC-1 and 2-methyoxyestradiol) results in delayed lymphatic repair, decreased local vascular endothelial growth factor-C (VEGF-C) expression, reduced numbers of VEGF-C(+) cells, and reductions in inflammatory lymphangiogenesis. Using transgenic HIF-1alpha/luciferase mice to image HIF 1alpha expression in real time in addition to Western blot analysis and pimonidazole staining for cellular hypoxia, we demonstrate that hypoxia stabilizes HIF-1alpha during initial stages of wound repair (1-2 wk); whereas inflammation secondary to gradients of lymphatic fluid stasis stabilizes HIF 1alpha thereafter (3-6 wk). In addition, we show that CD4(+) cell-mediated inflammation is necessary for this response and regulates HIF-1alpha expression by macrophages, as CD4-deficient or CD4-depleted mice demonstrate 2-fold reductions in HIF-1alpha expression as compared to wild-types. In summary, we show that HIF-1alpha is a critical coordinator of lymphangiogenesis by regulating the expression of lymphangiogenic cytokines as part of an early response mechanism to hypoxia, inflammation, and lymphatic fluid stasis. PMID- 22067483 TI - The ubiquitin hydrolase USP22 contributes to 3'-end processing of JAK-STAT inducible genes. AB - The JAK-STAT (Janus kinase-signal transducer and activator of transcription) signaling pathway drives cellular growth, differentiation, and the immune response. STAT-activated gene expression is both rapid and transient and requires dynamic post-translational modification of the chromatin template. We previously showed that monoubiquitination of histone H2B (ubH2B) is highly dynamic at the STAT1 target gene, interferon regulatory factor 1 (IRF1), suggesting that a deubiquitinase is recruited during gene activation. Here, we report that RNAi mediated knockdown of the ubiquitin hydrolase, USP22, results in 2-fold higher ubH2B, and 2-fold lower transcriptional elongation at IRF1. We also demonstrate that USP22 depletion diminishes 3'-end cleavage/polyadenylation by 2- to 3-fold. Furthermore, the polyadenylation factor CPSF73 is not effectively recruited, and serine 2 phosphorylation (Ser2P) of the C-terminal domain of RNA polymerase II is also disrupted. The transcriptional and processing defects observed in the USP22 knockdown cells are reversed by transient USP22 overexpression. Together, these results suggest that ubH2B helps recruit polyadenylation factors to STAT1 activated genes. We propose a working model, wherein a cycle of H2B ubiquitination/deubiquitination specifies Ser2P to regulate elongation and 3'-end processing of JAK-STAT-inducible mRNAs. These results further elaborate USP22 function and its role as a putative cancer stem cell marker. PMID- 22067484 TI - Evaluation of genomic high-throughput sequencing data generated on Illumina HiSeq and genome analyzer systems. AB - BACKGROUND: The generation and analysis of high-throughput sequencing data are becoming a major component of many studies in molecular biology and medical research. Illumina's Genome Analyzer (GA) and HiSeq instruments are currently the most widely used sequencing devices. Here, we comprehensively evaluate properties of genomic HiSeq and GAIIx data derived from two plant genomes and one virus, with read lengths of 95 to 150 bases. RESULTS: We provide quantifications and evidence for GC bias, error rates, error sequence context, effects of quality filtering, and the reliability of quality values. By combining different filtering criteria we reduced error rates 7-fold at the expense of discarding 12.5% of alignable bases. While overall error rates are low in HiSeq data we observed regions of accumulated wrong base calls. Only 3% of all error positions accounted for 24.7% of all substitution errors. Analyzing the forward and reverse strands separately revealed error rates of up to 18.7%. Insertions and deletions occurred at very low rates on average but increased to up to 2% in homopolymers. A positive correlation between read coverage and GC content was found depending on the GC content range. CONCLUSIONS: The errors and biases we report have implications for the use and the interpretation of Illumina sequencing data. GAIIx and HiSeq data sets show slightly different error profiles. Quality filtering is essential to minimize downstream analysis artifacts. Supporting previous recommendations, the strand-specificity provides a criterion to distinguish sequencing errors from low abundance polymorphisms. PMID- 22067485 TI - What part can nurses play in the prevention of suicide? AB - Professor Alan Glasper discusses the new goverment initiative which aims to tackle the number of suicides ocurring in the UK. There are many different reasons people choose to take their own lives and it is important that nurses have a good understanding and awareness of these in order to contribute to the reduction of the problem. PMID- 22067486 TI - NHS future forum: is anyone listening? AB - The NHS Future Forum has been asked by the Government to continue what it refers to as 'conversations' with patients, service users and professionals (Department of Health (DH), 2011a). The key focus points of the forum are information, education and training, integrated care and public health. The forum was first put into action following the publication of Modernising the NHS: The Health and Social Care Bill 2011 (DH, 2011b), which met with opposition from many who felt that encouraging competition within the NHS was a bad idea and put the NHS at risk of privatization. Andrew Lansley, Secretary of State for Health, launched a 'listening exercise' as a response to this widespread criticism. However, this too has been criticized after a confidential memo came to light suggesting that there was actually little room for manoeuvre in terms of changes to the Bill (Bosely et al, 2011). PMID- 22067487 TI - The importance of hand disinfection prior to surgery. AB - 'Hand washing is a practice we perform ritualistically, but as healthcare professionals we need to appreciate its importance in clinical practice and not become complacent about it' (Kerr, 1998). PMID- 22067488 TI - Inadvertant hypothermia and active warming for surgical patients. AB - Inadvertant hypothermia is common among surgical patients and can result in serious complications. This article describes active warming systems which can be used preoperatively and intraoperatively to prevent hypothermia and maintain normothermia (normal body temperature). PMID- 22067489 TI - Emergency and intensive care: assessing and managing the airway. AB - Airway assessment and management skills are vital in an emergency department (ED) as they are the most sensitive indicator of patient deterioration. Problems as common as head injury or alcohol intoxication are associated with an inadequate airway or diminished respiratory function and can cause a patient's condition to decline rapidly. Maintaining a patient's airway and facilitating breathing is the main priority in any emergency situation, although achieving airway control can be difficult. All health professionals need to be able to safely undertake airway management. The key is a thorough assessment to determine whether the airway is patent or not. This paper will discuss the importance and practicalities of airway management and assessment in the emergency and intensive care. PMID- 22067490 TI - The future of surgical nursing and enhanced recovery programmes. AB - Patients undergoing surgery in the UK are seeing a rise in the development of enhanced recovery programmes as a result of increasing medical advances. Enhanced recovery is concerned with helping patients get better sooner after an operation by following a meticulous regime of care. The practical application of these programmes is undertaken largely by nurses, despite encompassing explicit, medically-driven protocols. However, beyond the professional knowledge and skills required to aid the programmes, nursing knowledge has contributed little to this rapidly developing aspect of surgery to date. Nursing has much to offer through future creation of centrally coordinated, surgical nursing units focusing on patients' holistic experience. This article will briefly describe enhanced recovery, identify aspects of nursing knowledge that can have a positive influence, and outline practical changes to assist the development of such programmes, thereby benefiting all patients undergoing elective surgery. PMID- 22067491 TI - Hirsutism: causes and treatment for women. AB - Hirsutism is defined as an androgen-dependent, male pattern of hair distribution in women. It affects between 5-15% of all women across all ethnic backgrounds (Azziz, 2003). The presence of unwanted female facial hair (and male hair patterns in other body areas) is the devastating consequence of hirsutism. It is also estimated that up to 40% of the general female population have some degree of unwanted facial hair (Hamzavi et al, 2007). The treatment of hirsutism is twofold; treating the underlying cause and reducing visible hair. This article will seek to define the causes of hirsutism, explore current treatment options for the removal of unwanted hair and discuss the psychosocial effects for the woman with hirsutism. PMID- 22067492 TI - Fibromyalgia: an overview and comparison of treatment options. AB - Fibromyalgia is a common condition characterized by a multitude of physical and psychological symptoms which tend to persist overtime. The dominant symptom is that of widespread musculoskeletal pain. This paper discusses the possible causations of fibromyalgia, as well as the need for a biopsychosocial assessment to fully understand the pain experience and to inform treatment and the evidence base regarding therapeutic interventions. PMID- 22067493 TI - Why is the regulation of advanced practice essential? AB - For many years, nurses have sought to define advanced practice (AP). There is now a developing consensus that it should be broadly defined in ways which include and embrace not only clinical practice, but also other domains such as education, management and leadership. This broad definition is congruent with Benner's notion of the novice to expert trajectory and lends support to the view that the risks around AP are minimal, since advanced practitioners by definition have expertise. The broad model of AP, however, ignores one distinct subset of advanced practice nurses who we term nurse practitioners (NPs). NPs are distinct because of their hybrid, quasi-medical practice, which crucially involves autonomous medical diagnosis and treatment. The risks in this area of practice are substantial, and consequently require nothing less than a nationally regulated set of benchmarks. These must address the training, assessment and registration of NPs for the primary purpose of public protection. PMID- 22067494 TI - Supporting self and others: from staff nurse to nurse consultant. Part 8: dealing with negative staff. AB - One of the most destructive forces to teamwork and morale are people within the team who are negative. Everyone has days when they feel a bit 'down' and most people enjoy a bit of a coffee break moan, but a few seem to dedicate their lives to moaning and take this to an extreme, becoming a destructive negative element when working in a team. PMID- 22067495 TI - The Care Quality Commission's end-of-year report. AB - Annual reports of organizations are very useful, they portray the activities that have been carried out and also lay out plans for the future. Trends, challenges and opportunities for the organization and the sector are also identified. Annual reports are in many respects very similar to the end of year reports that we all received at school but perhaps not as blunt. The Care Quality Commission (CQC) annual report (the report) has just been published and it provides an illuminating picture of NHS care in England with many challenges, successes and failures clearly revealed. Key sections of the report that relate to NHS health care will be discussed in this article. PMID- 22067496 TI - Essential tips for nurses. AB - A useful book for teachers of nurses as well as for their pupils was reviewed in the BJN 100 years ago. It was called, 'A Quiz Book of Nursing,' by Miss Amy Elizabeth Pope, with regard to the restraint of patients, it is suggested that the following points should be emphasized by the instructor: PMID- 22067497 TI - Reviewing nurse safety in the aftermath of the riots. AB - Many cities in the UK including London, Birmingham and Manchester, were ravaged by the shocking levels of rioting and looting that took place a few weeks ago and are still attempting to recover. PMID- 22067498 TI - Care transitions: more important than ever and on the national agenda. PMID- 22067500 TI - OASIS-C importance of accurate pressure ulcer assessment and management in home healthcare: part II. AB - This is Part II of an article describing an educational initiative by certified wound, ostomy, and continence nurses to strengthen clinical and documentation skills related to the Outcome and Assessment Information Set (OASIS)-C M items. Part I, published in Home Healthcare Nurse in April 2011 (vol. 29, issue 4, pp. 233-245), reviewed the fundamentals of wound assessment, wound healing, and OASIS C wound terminology. The focus of this article is to show the connection between the clinical assessment, interventions, documentation, and the impact on quality outcomes and reimbursement. Because of the scope of this topic and the emphasis given to the problem of pressure ulcers by varying sectors of healthcare, including hospitals and nursing homes, this article focuses on pressure ulcers and OASIS-C. PMID- 22067502 TI - A call to action: helping hospice social workers embrace evidence-based practice improving hospice documentation. AB - Hospice programs provide interdisciplinary palliative care and services to patients with a life-limiting illness; 6 months or less if the disease runs its normal course. Social workers have been a required part of the hospice interdisciplinary group since the inception of the Hospice Medicare Benefit in 1983 (), and it is impossible to imagine hospice care without the involvement of social workers. Social workers are uniquely trained to assess the psychological and social factors that impact well-being and intervene when the inability to cope and emotional stress further impair the function of the patient and family. PMID- 22067504 TI - A systems-based medication reconciliation process: with implications for home healthcare. AB - This article describes the medication reconciliation process applied on hospital discharge of patients to home with home care services within Seton Health System, an integrated health delivery network located in Troy, New York. The project, which was not research based, was characterized by an intensive pharmacotherapeutic medication reconciliation at hospital discharge by the hospital-based pharmacist with continued pharmacist support available to home healthcare nurses collaboratively at the time of start of care and resumption of care. The goal of this process was to identify and resolve medication-related problems and reduce hospital readmissions. PMID- 22067505 TI - The challenge of improving transitional care: lessons learned in a home healthcare agency. AB - This article describes the efforts undertaken to reduce avoidable hospitalizations in a large, not-for-profit home healthcare agency over a period of 4 years by focusing on the improvement of transitional care-that is, moving patients from 1 level of care to another. Beginning as an effort to simply "teach" home care staff about best-practice tools, the challenges of implementing the changes required to improve the transition period were found to be complex and associated with a number of factors, ranging from the variation in discharge processes across hospitals to how clinicians perceived their roles and those of patients in the transition process. The author discusses the insights gleaned from the work that has been completed-and the work that still remains-while steadily decreasing the home healthcare agency's overall hospitalization rate. PMID- 22067506 TI - Research on transitional care: from hospital to home. AB - Concern over the human and financial costs of healthcare "silos" and poorly coordinated care has been growing, fueled by data on risky patient "handoffs," repeat hospitalizations, and avoidable emergency department visits. More than 20% of patients experience an adverse clinical event within 30 days of the discharge from a hospital (). This column features research and review articles focused on the issue of "handoffs" and transitional care. The investigators of the 1st article described studied communication and information transfer deficits between hospitalists and primary care physicians. The 2nd article presents findings of a systematic hospital-based intervention geared toward improving discharge experiences. The 3rd article describes another hospital-based initiative. This reengineered discharge intervention uses nurse discharge advocates as one component of a strategy to help patients understand, develop, and implement their discharge plans. The final article profiled in this column presents findings of a systematic literature review of randomized clinical trials that aimed to improve transitional care for chronically ill adults and opportunities to promote more widespread use of evidence-based programs through initiatives sponsored by the Patient Protection and Affordable Care Act. Interested readers are encouraged to read the articles for full information about the interventions and review findings. PMID- 22067507 TI - The complexity of care transitions. PMID- 22067508 TI - Olfactory projections in the lepidosirenid lungfishes. AB - Olfactory nerve and olfactory bulb projections in lepidosirenid lungfishes were experimentally determined with neural tracers. Unilateral injections of DiI into the olfactory nerve labeled the accessory and main olfactory bulbs as well as fibers of the anterior root of the terminal nerve, which terminates extensively in cell groups of the medial hemispheric wall, the dorsal and lateral pallia, and the preoptic nuclei and posterior tubercle. Lepidosirenid lungfishes do not exhibit separate vomeronasal nerves, but previous data indicate that calbindin positive receptors within basal crypts of the olfactory epithelium are homologous to the vomeronasal organ of tetrapods. Unilateral injections of DiI into the accessory olfactory bulb reveal an accessory olfactory tract which terminates primarily if not solely in the ipsilateral medial amygdalar nucleus as in amphibians. Unilateral injections of tracers into the main olfactory bulb reveal extensive projections to all cell groups in the ipsilateral telencephalic hemisphere, except for the medial amygdalar nucleus, as well as secondary olfactory projections (decussating in the habenular commissure) to the contralateral dorsal pallium and main olfactory bulb. Secondary olfactory projections also terminate bilaterally in diencephalic and midbrain centers after partial decussation in the anterior and postoptic commissures, as well as in the ventral hypothalamus and posterior tubercle. Cladistic analysis of the extensive secondary olfactory projections indicates that this pattern is primitive for all bony fishes whereas the reduction in secondary olfactory projections in amphibians, particularly anurans, is a derived, simplified pattern. PMID- 22067509 TI - Damping by branching: a bioinspiration from trees. AB - Man-made slender structures are known to be sensitive to high levels of vibration due to their flexibility which often cause irreversible damage. In nature, trees repeatedly endure large amplitudes of motion, mostly caused by strong climatic events, yet with minor or no damage in most cases. A new damping mechanism inspired by the architecture of trees is identified here and characterized in the simplest tree-like structure, a Y-shaped branched structure. Through analytical and numerical analyses of a simple two-degree-of-freedom model, branching is shown to be the key ingredient in this protective mechanism that we call damping by-branching. It originates in the geometrical nonlinearities so that it is specifically efficient to damp out large amplitudes of motion. A more realistic model, using flexible beam approximation, shows that the mechanism is robust. Finally, two bioinspired architectures are analyzed, showing significant levels of damping achieved via branching with typically 30% of the energy being dissipated in one oscillation. This concept of damping-by-branching is of simple practical use in the design of very slender and flexible structures subjected to extreme dynamical loadings. PMID- 22067510 TI - The importance of challenge for the enjoyment of intrinsically motivated, goal directed activities. AB - Although early interview-based analyses of the enjoyment of intrinsically motivated, goal-directed activities (e.g., chess, rock climbing, art making) suggested the importance of relatively difficult, "optimal" challenges, subsequent findings derived from a wider range of activities have not provided consistent support for this proposition. Two studies were conducted to clarify the relation between challenge and enjoyment. Study 1 focused on a single activity-Internet chess. The importance of challenge was evident at the subjective level (perceived challenge strongly predicted enjoyment) as well as the objective level (games against superior opponents were more enjoyable than games against inferior opponents, and close games were more enjoyable than blowouts). In Study 2, the experience sampling method was used to examine the enjoyment of challenge across a wide range of everyday activities. Activity motivation (intrinsically motivated, non-intrinsically motivated) and activity type (goal directed, non-goal directed) moderated the relation. Implications for theories of intrinsic motivation are discussed. PMID- 22067511 TI - Cardiac excitation mechanisms, wavefront dynamics and strength-interval curves predicted by 3D orthotropic bidomain simulations. AB - The assessment and understanding of cardiac excitation mechanisms is very important for the development and improvement of implantable cardiac devices, pacing protocols, and arrhythmia treatments. Previous bidomain simulation studies have investigated cathodal and anodal make/break mechanisms of cardiac excitation and strength-interval (S-I) curves in two-dimensional sheets or cylindrical domains, that by symmetry reduce to the two-dimensional case. In this work, cathodal and anodal S-I curves are studied by means of detailed bidomain simulations which include: (i) three-dimensional cardiac slabs; (ii) transmural fiber rotation; (iii) unequal orthotropic anisotropy of the conducting media; (iv) incorporation of funny and electroporation currents in the ventricular membrane model. The predicted shape of cathodal and anodal S-I curves exhibit the same features of the S-I curves observed experimentally and the break/make transition coincides with the final descending phase of the S-I curves. Away from the break/make transition, only the break or make excitation mechanism is observed independently of the stimulus strength, whereas within an interval at the break/make transition, new paradoxical excitation behaviors are observed that depend on the stimulus strength. PMID- 22067512 TI - Distinguishing possible mechanisms for auxin-mediated developmental control in Arabidopsis: models with two Aux/IAA and ARF proteins, and two target gene-sets. AB - New models of gene transcriptional responses to auxin signalling in Arabidopsis are presented. This work extends a previous model of auxin signalling to include networks of gene-sets which may control developmental responses along auxin gradients. Key elements of this new study include models of signalling pathways and networks involving two Aux-IAA proteins (IAAs), auxin response factors (ARFs) and gene targets. Hypotheses for the gene network topologies which may be involved in developmental responses have been tested against experimental observations for root hair growth in particular. In studying these models, we provide a framework for the analysis of auxin signalling with multiple IAAs and ARFs, and discuss the implications of bistability in such systems. PMID- 22067513 TI - Preconditions for successful guideline implementation: perceptions of oncology nurses. AB - BACKGROUND: Although evidence-based guidelines are important for improving the quality of patient care, implementation in practice is below expectations. With the recent focus on team care, guidelines are intended to promote the integration of care across multiple disciplines. We conducted an exploratory study to understand oncology nurses' perceptions of guideline implementation and to learn their views on how their experiences affected the implementation. METHODS: A qualitative study was used with focus group interviews. We collected data from 11 nurses with more than 5 years of oncology nursing experience in Japan. The data were analyzed using grounded theory. RESULTS: Results of the analysis identified "preconditions for successful guideline implementation" as a core category. There were 4 categories (goal congruence, equal partnership, professional self development and user-friendliness) and 11 subcategories related to organizational, multidisciplinary, individual, and guideline levels. CONCLUSIONS: Although the guidelines were viewed as important, they were not fully implemented in practice. There are preconditions at the organizational, multidisciplinary, individual, and guideline levels that must be met if an organization is to successfully implement the guideline in clinical settings. Prioritizing strategies by focusing on these preconditions will help to facilitate successful guideline implementation. PMID- 22067514 TI - The endometrial epigenome and its response to steroid hormones. AB - The human endometrium undergoes cyclic morphological and functional changes during the menstrual cycle. These changes are driven mainly by steroid hormones and orchestrated by a myriad of genes - many of which have been identified recently as being epigenetically regulated. Epigenetic modifications, including DNA methylation and histone acetylations, are shown recently to be involved in functional changes in endometrium and endometrial diseases. Since epigenetics itself is a rapidly evolving field, this review starts with an overview of epigenetics and its intrinsic connections with endometrial response to steroid hormones, highlighting its various levels of complexities. This is followed by a review of published and unpublished work on "writers", "erasers", and other players of endometrial epigenome. In the end, areas in need for future research in this area will be exposed. PMID- 22067515 TI - DNA fingerprinting of Mycobacterium tuberculosis: from phage typing to whole genome sequencing. AB - Current typing methods for Mycobacterium tuberculosis complex evolved from simple phenotypic approaches like phage typing and drug susceptibility profiling to DNA based strain typing methods, such as IS6110-restriction fragment length polymorphisms (RFLP) and variable number of tandem repeats (VNTR) typing. Examples of the usefulness of molecular typing are source case finding and epidemiological linkage of tuberculosis (TB) cases, international transmission of MDR/XDR-TB, the discrimination between endogenous reactivation and exogenous re infection as a cause of relapses after curative treatment of tuberculosis, the evidence of multiple M. tuberculosis infections, and the disclosure of laboratory cross-contaminations. Simultaneously, phylogenetic analyses were developed based on single nucleotide polymorphisms (SNPs), genomic deletions usually referred to as regions of difference (RDs) and spoligotyping which served both strain typing and phylogenetic analysis. National and international initiatives that rely on the application of these typing methods have brought significant insight into the molecular epidemiology of tuberculosis. However, current DNA fingerprinting methods have important limitations. They can often not distinguish between genetically closely related strains and the turn-over of these markers is variable. Moreover, the suitability of most DNA typing methods for phylogenetic reconstruction is limited as they show a high propensity of convergent evolution or misinfer genetic distances. In order to fully explore the possibilities of genotyping in the molecular epidemiology of tuberculosis and to study the phylogeny of the causative bacteria reliably, the application of whole-genome sequencing (WGS) analysis for all M. tuberculosis isolates is the optimal, although currently still a costly solution. In the last years WGS for typing of pathogens has been explored and yielded important additional information on strain diversity in comparison to the classical DNA typing methods. With the ongoing cost reduction of DNA sequencing it is possible that WGS will become the sole diagnostic tool in the secondary laboratory diagnosis of tuberculosis for identification, drug susceptibility testing and genetic characterization. PMID- 22067516 TI - Recombinant norovirus GII.g/GII.12 gastroenteritis in children. AB - Recombinant GII.g/GII.12 norovirus (NoV) strains emerged in 2008 in Australia and subsequently have been associated with gastroenteritis outbreaks worldwide. In the winter season 2009-2010 GII.12 strains caused 16% of the NoV outbreaks in the United States. During 2009-2010 we also identified GII.g/GII.12 strains during surveillance of sporadic cases of gastroenteritis in Italian children. Severity scores were calculated for the GII.g/GII.12 NoV infections using the Vesikari scale and in two out of three paediatric cases they exceeded the median value calculated for concomitant GII.4 infections. Upon sequence analysis, the Italian strains were found to be recombinant viruses and displayed different patterns of nucleotide polymorphisms. Phylodynamic analysis with other GII.g/GII.12 recombinants showed a high rate of evolution, comparable to the rates observed for GII.4 viruses. The mechanisms leading to worldwide emergence of GII.12 NoV strains in 2008-2010 are not clear. Monitoring of GII.12 NoV circulation is necessary to understand these mechanisms of evolution. PMID- 22067517 TI - Reactive lymphoid hyperplasia of the ocular surface: clinicopathologic features and search for infectious agents. PMID- 22067518 TI - Clinical features of patients with immunoglobulin light chain amyloidosis (AL) with vascular-limited deposition in the kidney. AB - In the kidney, immunoglobulin light chain amyloidosis (AL) can be deposited in vascular-limited AL (V-AL) or diffuse (D-AL) pattern. These patterns are associated with different clinical presentations. A nested case study was performed to describe these differences. V-AL was defined by the vascular-limited deposits. Cases were matched for age, sex and date of renal biopsy. There were 12 cases of V-AL (mean age 61 +/- 11 years) and 24 cases of D-AL. Median follow-up was 26 months for V-AL and 38 months for D-AL, P = 0.14. Lambda was more common in D-AL (83.3%) than V-AL (50%, P = 0.04). Cardiac function was similar between the two groups. V-AL patients presented with lower renal function (serum creatinine = 2.1 versus 1.3 mg/dL, P = 0.02; estimated glomerular filtration rate 31 versus 59 mL/min/1.73m(2), P = 0.01 and creatinine clearance 38.5 versus 64 mL/min/1.73m(2), P = 0.02, respectively). Proteinuria was low grade in V-AL [0.4 (0.09-0.98) g/day] compared to nephrotic range in D-AL patients [8.0 (0.2-22) g/day, P < 0.001]. Stem cell transplantation was performed on 62.5% of the D-AL but on only 25% of the V-AL, P = 0.08. Median survival was longer in patients with D-AL (77.2 months) versus V-AL (40.6 months, log-rank P = 0.02). Our study found that V-AL patients presented with more severe renal insufficiency and less proteinuria than D-AL. There was a preference for lambda light chain in the D-AL that was not noted in the V-AL. Patients with D-AL in this study had a longer median survival but most of them were stem cell transplantation candidates. PMID- 22067519 TI - Body plan in tetrapods: is it patterned by a hyperbolic tissue flow? PMID- 22067520 TI - Levosimendan in two neonates with ischemic heart failure and pulmonary hypertension. AB - We report the successful and safe use of levosimendan, a new calcium-sensitizing agent with positive inotropic and vasodilatory action, in 2 critically ill term newborns with acute heart failure and pulmonary hypertension in the absence of any underlying heart malformation and/or previous cardiosurgical procedures. During the neonatal period, levosimendan may represent an ideal drug for immature myocardium characterized by a higher calcium-dependent contractility than in adults. PMID- 22067526 TI - Is the intake of sugar-containing beverages during adolescence related to adult weight status? AB - OBJECTIVE: To investigate the relationship between the intake of sugar-containing beverages (SCB) at the age of 13 years and adult weight status 24-30 years later. DESIGN: A longitudinal study with 30 years of follow-up from adolescence (age 13 years in 1976) to adulthood (up to 2000 and 2006). Dietary intake was assessed through cross-check dietary history face-to-face interviews by a dietitian. Beverages were divided into two categories: (i) total SCB and (ii) SCB excluding 100% fruit juices. Percentage of total fat (%total fat) and percentage of trunk fat (%trunk fat) were obtained through dual-energy X-ray absorptiometry measurements; body weight and height were measured by trained staff. SETTING: Amsterdam Growth and Health Longitudinal Study, the Netherlands. SUBJECTS: One hundred and fourteen males and 124 females. RESULTS: In males, but not in females, each additional daily serving of SCB excluding 100% fruit juices at 13 years was associated with 1?14% higher %total fat (95% CI 0?04, 2?23 %; P50?04) and 1?62% higher %trunk fat (95% CI 0?14, 3?10 %; P50?03) in adulthood after correction for confounders. No statistically significant relationship was found between the intake of SCB excluding 100% fruit juices at the age of 13 and BMI in both sexes. In addition, no statistically significant relationships were found between the intake of total SCB and all measures of adult weight status in both sexes. CONCLUSIONS: Intake of SCB excluding 100% fruit juices at the age of 13 years was positively associated with adult %total fat and %trunk fat in males, but not in females. PMID- 22067527 TI - Development of a novel, nearly insoluble antiadhesive membrane. AB - BACKGROUND: Sodium hyaluronate/carboxymethylcellulose (HA/CMC) is difficult to use in a moist environment because of its susceptibility to moisture. METHODS: We developed the three-layered nDM-14R membrane. The surface layers are composed of 1-lactide, glycolide and e-caprolactone copolymers. HA/CMC and nDM-14R were used in all these studies. (1) The central region of 1 * 10 cm specimens (n = 5) was moistened for 0, 5, 10, 20, 30 or 60 s, after which the tensile strength was determined; (2) one side of specimens of 1 * 10 cm (n = 5) was moistened with agar gel for 5, 10, 15 or 30 s, after which the adhesion strength was determined, and (3) Rat cecum (n = 10) was scratched, 3 * 3 cm specimens were placed on the scratched area, and adhesions were evaluated on postoperative day 14. RESULTS AND CONCLUSION: (1) The tensile strength of nDM-14R after contact for 10-30 s was greater than that of HA/CMC. (2) The adhesive strength of HA/CMC after contact for 5-10 s was greater than that of nDM-14R. (3) Adhesion scores in treatment groups were significantly lower than in the control group. The results suggest that nDM-14R has the same antiadhesive effect and allows easier placement under moist conditions than HA/CMC. PMID- 22067528 TI - Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma. AB - BACKGROUND: Diagnosis of ductal carcinoma in situ (DCIS) in breast cancer cases is challenging for pathologist due to a variety of in situ patterns and artefacts, which could be misinterpreted as stromal invasion. Microinvasion is detected by the presence of cytologically malignant cells outside the confines of the basement membrane and myoepithelium. When malignant cells invade the stroma, there is tissue remodeling induced by perturbed stromal-epithelial interactions. Carcinoma-associated fibroblasts (CAFs) are main cells in the microenvironment of the remodeled tumor-host interface. They are characterized by the expression of the specific fibroblast activation protein-alpha (FAP-alpha), and differ from that of normal fibroblasts exhibiting an immunophenotype of CD34. We hypothesized that staining for FAP-alpha may be helpful in determining whether DCIS has microinvasion. METHODS: 349 excised breast specimens were immunostained for smooth muscle actin SMA, CD34, FAP-alpha, and Calponin. Study material was divided into 5 groups: group 1: normal mammary tissues of healthy women after plastic surgery; group 2: usual ductal hyperplasia (UDH); group 3: DCIS without microinvasion on H & E stain; group 4: DCIS with microinvasion on H & E stain (DCIS-MI), and group 5: invasive ductal carcinoma (IDC). A comparative evaluation of the four immunostains was conducted. RESULTS: Our results demonstrated that using FAP-alpha and Calponin adjunctively improved the sensitivity of pathological diagnosis of DCIS-MI by 11.29%, whereas the adjunctive use of FAP alpha and Calponin improved the sensitivity of pathological diagnosis of DCIS by 13.6%. CONCLUSIONS: This study provides the first evidence that immunostaining with FAP-alpha and Calponin can serve as a novel marker for pathologically diagnosing whether DCIS has microinvasion. PMID- 22067530 TI - Emotion modulates cognitive flexibility in patients with major depression. AB - BACKGROUND: Depression is associated with alterations of emotional and cognitive processing, and executive control in particular. Previous research has shown that depressed patients are impaired in their ability to shift attention from one emotional category to another, but whether this shifting deficit is more evident on emotional relative to non-emotional cognitive control tasks remains unclear. METHOD: The performance of patients with major depressive disorder and matched healthy control participants was compared on neutral and emotional variants of a dynamic cognitive control task that requires participants to shift attention and response from one category to another. RESULTS: Relative to controls, depressed patients were impaired on both tasks, particularly in terms of performance accuracy. In the neutral go/no-go task, the ability of depressed patients to flexibly shift attention and response from one class of neutral stimuli to the other was unimpaired. This contrasted with findings for the emotional go/no-go task, where responding was slower specifically on blocks of trials that required participants to shift attention and response from one emotional category to the other. CONCLUSIONS: The present data indicate that any depression-related difficulties with cognitive flexibility and control may be particularly evident on matched tasks that require processing of relevant emotional, rather than simply neutral, stimuli. The implications of these findings for our developing understanding of cognitive and emotional control processes in depression are discussed. PMID- 22067531 TI - As we look toward the future, should we take note of the past? PMID- 22067529 TI - Chemical and transcriptional responses of Norway spruce genotypes with different susceptibility to Heterobasidion spp. infection. AB - BACKGROUND: Norway spruce [Picea abies (L.) Karst.] is one of the most important conifer species in Europe. The wood is economically important and infections by wood-rotting fungi cause substantial losses to the industry.The first line of defence in a Norway spruce tree is the bark. It is a very efficient barrier against infection based on its mechanical and chemical properties. Once an injury or an infection is recognized by the tree, induced defences are activated. In this study we examined transcriptional response, using 454-sequencing, and chemical profiles in bark of Norway spruce trees with different susceptibility to Heterobasidion annosum s.l. infection. The aim was to find associations between the transcriptome and chemical profiles to the level of susceptibility to Heterobasidion spp. in Norway spruce genotypes. RESULTS: Both terpene and phenol compositions were analysed and at 28 days post inoculation (dpi) high levels of 3 carene was produced in response to H. annosum. However, significant patterns relating to inoculation or to genotypes with higher or lower susceptibility could only be found in the phenol fraction. The levels of the flavonoid catechin, which is polymerized into proanthocyanidins (PA), showed a temporal variation; it accumulated between 5 and 15 dpi in response to H. annosum infection in the less susceptible genotypes. The transcriptome data suggested that the accumulation of free catechin was preceded by an induction of genes in the flavonoid and PA biosynthesis pathway such as leucoanthocyanidin reductase. Quantitative PCR analyses verified the induction of genes in the phenylpropanoid and flavonoid pathway. The qPCR data also highlighted genotype-dependent differences in the transcriptional regulation of these pathways. CONCLUSIONS: The varying dynamics in transcriptional and chemical patterns displayed by the less susceptible genotypes suggest that there is a genotypic variation in successful spruce defence strategies against Heterobasidion. However, both high levels of piceasides and flavonoids in the less susceptible genotypes suggested the importance of the phenolic compounds in the defence. Clearly an extended comparison of the transcriptional responses in the interaction with Heterobasidion between several independent genotypes exhibiting reduced susceptibility is needed to catalogue mechanisms of successful host defence strategies. PMID- 22067532 TI - Managing pain in obese patients. AB - Obesity has become an epidemic in American healthcare. Comorbidities such as diabetes and cardiac disease increase the mortality and morbidity for these patients. Obesity-related pain conditions can limit the patient's efforts at increasing activity and limit quality of life. This article will offer information on these conditions and treatment options. PMID- 22067533 TI - Anthracycline extravasations: prevention and management. AB - This article highlights the importance of being knowledgeable about anthracycline extravasations, including their prevention, early detection, and prompt and effective management. It also emphasizes the need for chemotherapy nurses to document and report all extravasations when they occur, summarizes the current management options, and offers recommendations for clinical practice. Extravasation refers to the unintentional administration of an agent into the surrounding tissue instead of the venous system; in this case, vesicant chemotherapy. Anthracycline extravasations can lead to significant and lasting tissue damage, infection, pain, and functional impairment; they remain a feared consequence for both the patient receiving the chemotherapy and the nurse administering it. The management of anthracycline extravasations remains a constant challenge to the professionals caring for the patient. One of these challenges is the lack of evidence for many of the treatment options available. The systemic antidote Savene(r) is the only approved treatment for anthracycline extravasations. It has proved highly efficacious and well-tolerated in prospective clinical studies and in routine clinical practice. Despite national and international professional organizations recommending Savene in their extravasation guidelines, many cancer networks in England still exclude it from their local protocol. Funding decisions regarding the use of supportive treatments are often made on the basis of clinical need; it is, therefore, imperative that nurses promptly report all extravasations or they will remain unknown and management of extravasations will not improve. PMID- 22067534 TI - Clinical nurse specialists: essential resource for an effective NHS. AB - Despite emerging evidence for the clinical and financial efficacy of the clinical nurse specialist (CNS), the provision of this role is patchy across the country. There is also a risk that incumbent CNS' may be redirected to less specialist work in trusts that do not appreciate the full value of the service that these nurses provide. Optimal and equitable patient access to CNS care will require the development of a strong evidence base showing that specialist nurses not only deliver patient-focused care, but that they can also help to meet healthcare managers' objectives of streamlined, cost-effective clinical services. PMID- 22067535 TI - It's a targeted world in non-Hodgkin's lymphoma. PMID- 22067536 TI - Cancer nurses: value for money when it matters. PMID- 22067537 TI - Young patients with chronic lymphocytic leukaemia. PMID- 22067538 TI - Cancer-related fatigue: physical assessment is not enough. AB - Cancer-related fatigue has been referred to as 'inevitable, unimportant and untreatable' (Stone et al, 2000), with patient experiences easily overlooked or even dismissed by health professionals. This article examines literature regarding the prevalence of cancer-related fatigue, its manifestation and assessment. It also aims to encourage fellow health professionals to reflect on their own practice when assessing and managing fatigue, and identifies the need to address the psychosocial dimensions of the experience, as well as the physical. PMID- 22067539 TI - The WHO analgesic ladder: 25 years on. PMID- 22067540 TI - Effectively managing chemotherapy-induced nausea and vomiting. AB - This article examines the unpleasant side effect of chemotherapy-induced nausea and vomiting (CINV). What was once the main reason for withdrawing from treatment is now much more tolerable owing to the advent of modern antiemetics. However, because of the improvements in these antiemetics, the focus on CINV appears to have lapsed. Despite this, some patients continue to experience problems and under-report this side effect. This article looks at the mechanism of CINV and clarifies terminology and definitions surrounding it. Risk factors are discussed and management strategies advised, including appropriateness of modern antiemetics and non-pharmacological strategies. To conclude, a brief look at nursing implications and self-management strategies are explored. PMID- 22067542 TI - Hypertrophy and dietary tyrosine ameliorate the phenotypes of a mouse model of severe nemaline myopathy. AB - Nemaline myopathy, the most common congenital myopathy, is caused by mutations in genes encoding thin filament and thin filament-associated proteins in skeletal muscles. Severely affected patients fail to survive beyond the first year of life due to severe muscle weakness. There are no specific therapies to combat this muscle weakness. We have generated the first knock-in mouse model for severe nemaline myopathy by replacing a normal allele of the alpha-skeletal actin gene with a mutated form (H40Y), which causes severe nemaline myopathy in humans. The Acta1(H40Y) mouse has severe muscle weakness manifested as shortened lifespan, significant forearm and isolated muscle weakness and decreased mobility. Muscle pathologies present in the human patients (e.g. nemaline rods, fibre atrophy and increase in slow fibres) were detected in the Acta1(H40Y) mouse, indicating that it is an excellent model for severe nemaline myopathy. Mating of the Acta1(H40Y) mouse with hypertrophic four and a half LIM domains protein 1 and insulin-like growth factor-1 transgenic mice models increased forearm strength and mobility, and decreased nemaline pathologies. Dietary L-tyrosine supplements also alleviated the mobility deficit and decreased the chronic repair and nemaline rod pathologies. These results suggest that L-tyrosine may be an effective treatment for muscle weakness and immobility in nemaline myopathy. PMID- 22067543 TI - IETS 2011 pre-Conference Symposium foreword. PMID- 22067544 TI - Incidence of isolated heparin-induced thrombocytopenia and risk of thrombosis by IgG-specific anti-PF4/heparin ELISA. AB - Heparin-induced thrombocytopenia (HIT) antibodies are screened by an enzyme linked immunosorbent assay (ELISA). Polyspecific ELISA detects anti-PF4/heparin IgG, IgA, and IgM. Recently, anti-PF4/heparin IgG ELISA has been shown to be more specific. However, the impact of using the IgG-ELISA on the incidence of isolated HIT (thrombocytopenia alone without clinically evident thrombosis) and the risk of developing subsequent thrombosis are still unknown. METHODS: A total of 492 consecutive patients with clinically suspected HIT at The University of Texas Southwestern Medical Center and affiliated hospitals were retrospectively reviewed from December 2008 to May 2010. RESULTS: 29 patients (6%) were diagnosed with HIT based on clinical findings and positive ELISA. 19 of the 29 patients (65%) had thrombosis at the time of diagnosis; whereas 10 of the 29 (35%) had only isolated HIT. The ten patients with isolated HIT had serial follow up for at least 3 months. 3 of 10 were treated with direct thrombin inhibitors and 5 of 10 were treated with Warfarin for at least 1 month upon discharge. None of them developed symptoms or signs of thrombosis during 3 months of follow up. CONCLUSION: The incidence of isolated HIT in this study was 35%, which is significantly lower than previously reported in the literature. It is possible that some patients previously thought to have HIT by the poly-specific ELISA assay had false positive results. The improved specificity of the IgG- ELISA appears to reduce the incidence of isolated HIT which may have lower risk of subsequent thrombosis. PMID- 22067545 TI - Deep venous thrombosis in acute stroke patients. AB - Deep venous thrombosis (DVT) is a complication of stroke. Our aim was to determine the frequency of DVT in patients with acute stroke, risk factors for its development, and its influence on the 3-month outcome. A total of 323 consecutive patients with acute stroke were enrolled. We performed ultrasound imaging within 7 days after stroke. Deep venous thrombosis was found in 8.7% of patients, only in those with ischemic stroke. Patients with DVT were more frequently female (71.4% vs 49.5%), had prestroke Modified Rankin scale (mRS) 3 to 5 (42.9% vs 15.3%), elevated C-reactive protein (CRP) serum level (65.4% vs 32.5%), and a trend toward elevated serum fibrinogen level (85.7% vs 70.1%; P = .08). In a multivariate analysis, elevated CRP (odds ratio [OR] 3.15) and prestroke disability (OR 2.89) were independent risk factors for DVT. Deep venous thrombosis occurs in <10% of patients with acute stroke and does not significantly affect the 3-month outcome. Prestroke dependency and elevated CRP level at baseline are independent risk factors for DVT. PMID- 22067546 TI - Four-terminal resistance of an interacting quantum wire with weakly invasive contacts. AB - We analyze the behavior of the four-terminal resistance, relative to the two terminal resistance of an interacting quantum wire with an impurity, taking into account the invasiveness of the voltage probes. We consider a one-dimensional Luttinger model of spinless fermions for the wire. We treat the coupling to the voltage probes perturbatively, within the framework of non-equilibrium Green function techniques. Our investigation unveils the combined effect of impurities, electron-electron interactions and invasiveness of the probes on the possible occurrence of negative resistance. PMID- 22067548 TI - Attitudes toward people with disabilities caused by illness or injury: beyond physical impairment. AB - This study examined differences in attitudes toward and reactions to individuals with comparable disabilities caused by injury or illness. Participants were students and healthcare professionals randomly assigned to read one of eight vignettes constructed in a between-subjects, full-factorial design: 2 (illness/injury)* 2 (male/female)* 2 (visible/not visible). Participants completed questionnaires measuring reactions to the target person and attitudes toward people with disabilities. We found that both students and healthcare professionals expressed more positive attitudes toward persons with injury related compared with illness-related disabilities, but that these differences were typically not expressed in reported social encounters with individual disabled persons. The effects of the illness-injury distinction were moderated by sex only among students, with the highest distancing reported from a female with an illness-related disability. Visibility of the disability triggered more social distancing among students, regardless of the injury-illness distinction. We concluded that the illness-injury distinction is a socially and psychologically significant factor. PMID- 22067547 TI - The virulence regulator Agr controls the staphylococcal capacity to activate human neutrophils via the formyl peptide receptor 2. AB - The Agr quorum-sensing system represents the master regulator for staphylococcal virulence factors and is known to have a strong impact on the release of pathogen associated molecular pattern (PAMP) molecules. Among the various staphylococcal PAMPs, phenol-soluble modulin (PSM) peptides have attracted increasing interest because they are crucial for staphylococcal virulence and have neutrophil recruiting properties. The latter depend on recognition of PSMs by the neutrophil formyl peptide receptor 2 (FPR2/ALX), for which PSMs are highly efficient agonists. We demonstrate that Agr inactivation in Staphylococcus aureus or S. epidermidis leads to strongly reduced neutrophil responses, which is in agreement with the previously reported strict control of PSM expression by Agr. Agr had a distinct and profound impact on activation of FPR2/ALX but not of the related FPR1 receptor that senses bacterial formylated peptides. S. epidermidis PSMs had similar FPR2/ALX-activating properties but differed in their dependence on N terminal formylation compared to S. aureus PSMs. Moreover, S. aureus and S. epidermidis PSMs upregulated the neutrophil complement receptor CD11b via FPR2/ALX stimulation in an Agr-dependent fashion. Hence, Agr controls the capacity of staphylococcal pathogens to activate FPR2/ALX-dependent neutrophil responses, underscoring the crucial role of FPR2/ALX and PSMs in staphylococcus host interaction. PMID- 22067541 TI - Neurological diseases and pain. AB - Chronic pain is a frequent component of many neurological disorders, affecting 20 40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain. PMID- 22067549 TI - Rehabilitation of critical illness polyneuropathy and myopathy patients: an observational study. AB - Critical illness polyneuropathy and myopathy (CIPNM) frequently develops in patients hospitalized in intensive care units. The number of patients with CIPNM admitted to inpatient rehabilitation is increasing. The aim of this study was to comprehensively evaluate the outcome of their rehabilitation. Twenty-seven patients with CIPNM were included in the study. The diagnosis was established clinically and confirmed electrophysiologically. Manual muscle testing was used for the assessment of function. Activity was assessed using the functional independence measure and two walking tests. The patients were also assessed using an adapted International Classification of Functioning, Disability and Health (ICF) checklist. All assessments were performed at admission and discharge. Clinically important and statistically significant improvements were found in all observed measures. High and significant correlations were found between the measures, except between muscle strength and the results of walking tests. Improvement in body functions during rehabilitation decreased as the time from established diagnosis to the start of rehabilitation increased, but it was not related to rehabilitation duration. Improvements in terms of the ICF mainly corresponded to the gain in functional independence measure scores. Major improvement regarding body functions and activities/participation was achieved in patients with CIPNM with a relatively short rehabilitation. Rehabilitation of such patients should start as early as possible once the diagnosis has been established. Comprehensive assessment of such patients combining established scales, objective clinical tests, and the ICF is recommended. PMID- 22067550 TI - Effect of long-term physical activity practice after cardiac rehabilitation on some risk factors. AB - The objective of this study was to evaluate the effects of long-term physical activity practice after a cardiac rehabilitation program on weight, physical capacity and arterial compliance. The Dijon Physical Activity Score was used to identify two groups: sedentary and active. Weight, distance at the 6-min walk test and the small artery elasticity indice were measured at the beginning, at the end of the rehabilitation program and at 18.3 +/- 5.3 months after. After the cardiac rehabilitation, sedentary patients showed a significant increase in weight and a significant reduction in distance on the 6-min walk test and in the arterial compliance. Active patients did not show any alteration in these parameters. We concluded that, after a cardiac rehabilitation program, the sedentary lifestyle has a negative influence on weight, physical capacity and arterial compliance, which are major markers of risk factors. In contrast, the practice of physical activity preserves these parameters. PMID- 22067551 TI - When control fails: influence of the prefrontal but not striatal dopaminergic system on behavioural flexibility in a change detection task. AB - There is growing interest in understanding the neurobiological foundations of attention. To examine whether attentional processes in a change detection task are modulated by dopamine signalling, we investigated the influence of two polymorphisms, i.e. Val158Met (rs4680) in the catechol-O-methyl transferase (COMT) and a variable number of tandem repeats polymorphism (VNTR, rs28363170) in the dopamine transporter (DAT1). The COMT Met allele, which results in lower enzyme activity and therefore probably enhanced PFC dopamine signalling, was significantly associated with task-performance and modulated executive control: Homozygous Met/Met allele carriers had difficulties when performing a change detection task, particularly showing the greatest difficulties in case cognitive and behavioural flexibility was necessary and the required reaction was not part of the subject's primary task set. Contrary, no difference between the two genotype groups were evident, when an attentional conflict emerged and attentional control was needed for adequate responding. No association with variation in DAT1 was observed. The results indicate a dissociation of the prefrontal and striatal dopamine system for attentional control and behavioural flexibility in a change detection task: While prefrontal dopamine turnover seems to modulate performance, putatively via difficulties in set shifting leading to behavioural inflexibility in COMT Met allele carriers, striatal dopamine turnover seems less important in this regard. With respect to other studies examining mechanisms of attentional functions in different paradigms, the results suggest that behavioural flexibility and attentional control as two executive subprocesses are differentially influenced by genetic polymorphisms within the dopaminergic system. This article is part of a Special Issue entitled 'Post Traumatic Stress Disorder'. PMID- 22067552 TI - A case-referent study of lung cancer and incense smoke, smoking, and residential radon in Chinese men. AB - BACKGROUND: Burning incense generates large amounts of air pollutants, many of which are confirmed or suspected human lung carcinogens. OBJECTIVES: We conducted a population-based case-referent study to examine the effect of incense smoke exposure on lung cancer risk among Chinese males and explored the joint effect of cigarette smoking and exposure to residential radon. METHODS: We recruited 1,208 male lung cancer incident cases and 1,069 community referents from 2004 to 2006 and estimated their lifetime exposures to incense smoke and other residential indoor air pollutants based on self-reported information collected during interviews. We performed unconditional multivariable logistic regression analysis to estimate the odds ratio (OR) for lung cancer associated with exposure to incense smoke after adjusting for possible confounders. We conducted stratified analyses by smoking status and exposures to incense burning and residential radon and explored the potential additive-scale interactions. RESULTS: We observed an association between incense exposure and lung cancer that was limited primarily to smokers. Cigarette smoking and high cumulative incense exposure at home appeared to have a synergistic effect on lung cancer (compared with never-smokers who never used incense, the OR for lung cancer for smokers who used incense >= 60 day-years = 5.00; 95% confidence interval: 3.34, 7.51). Power was limited, but we also found preliminary evidence suggesting that radon exposure may increase risk among smokers using incense. CONCLUSION: Our study suggests that exposure to incense smoke in the home may increase the risk of lung cancer among smokers and that exposure to radon may further increase risk. PMID- 22067553 TI - Ultrasound-assisted synthesis of Li-rich mesoporous LiMn2O4 nanospheres for enhancing the electrochemical performance in Li-ion secondary batteries. AB - The hierarchically structured mesoporous LiMn(2)O(4) (LMO) nanospheres were synthesized using a template-free self-assembly process that was coupled with ultrasound (U). The ultrasound technique suggested here is very powerful for controlling an ordered nanostructure and improving crystallinity with large single-crystalline domains. Owing to the hierarchical mesoporous structure and high crystallinity, U-LMO provides an excellent rate capability and cycle stability with a capacity retention of more than 98% up to 50 cycles at a 0.2C rate. Here, we demonstrate that mesoporous U-LMO nanospheres were fabricated to enhance the electrochemical performance and protect it from structurally significant collapsing because of high crystallinity. PMID- 22067555 TI - Biomarkers predicting tumor response and evasion to anti-angiogenic therapy. AB - No fully validated biological markers currently exist to predict responsiveness to or the development of evasion to anti-angiogenic therapy of cancer. The identification of such biomarkers is vital to move these therapies forward, as failure to respond to these treatments is often associated with rapid tumor progression that could have been averted had the intrinsic or acquired evasion to anti-angiogenic therapy been identified in a timely fashion. Furthermore, the high cost of antiangiogenic therapies makes it important to avoid utilizing them in the setting of lack of response or developing evasion, making the identification of biomarkers even more important. A number of potential physiologic, circulating, tissue, and imaging biomarkers have emerged from recently completed preclinical animal studies and clinical trials. In this review, we define 5 different types of biomarkers (physiologic, circulating, intratumoral, genetic polymorphisms, and radiographic); discuss the challenges in establishing biomarkers of antiangiogenic therapy in animal models and in clinical trials; and discuss future strategies to identify and validate biomarkers of anti-angiogenic therapy. PMID- 22067554 TI - A novel esterase gene cloned from a metagenomic library from neritic sediments of the South China Sea. AB - BACKGROUND: Marine microbes are a large and diverse group, which are exposed to a wide variety of pressure, temperature, salinity, nutrient availability and other environmental conditions. They provide a huge potential source of novel enzymes with unique properties that may be useful in industry and biotechnology. To explore the lipolytic genetic resources in the South China Sea, 23 sediment samples were collected in the depth < 100 m marine areas. RESULTS: A metagenomic library of South China Sea sediments assemblage in plasmid vector containing about 194 Mb of community DNA was prepared. Screening of a part of the unamplified library resulted in isolation of 15 unique lipolytic clones with the ability to hydrolyze tributyrin. A positive recombinant clone (pNLE1), containing a novel esterase (Est_p1), was successfully expressed in E. coli and purified. In a series of assays, Est_p1 displayed maximal activity at pH 8.57, 40 degrees C, with rho-Nitrophenyl butyrate (C4) as substrate. Compared to other metagenomic esterases, Est_p1 played a notable role in specificity for substrate C4 (kcat/Km value 11,500 S-1m M-1) and showed no inhibited by phenylmethylsulfonyl fluoride, suggested that the substrate binding pocket was suitable for substrate C4 and the serine active-site residue was buried at the bottom of substrate binding pocket which sheltered by a lid structure. CONCLUSIONS: Esterase, which specificity towards short chain fatty acids, especially butanoic acid, is commercially available as potent flavoring tools. According the outstanding activity and specificity for substrate C4, Est_p1 has potential application in flavor industries requiring hydrolysis of short chain esters. PMID- 22067557 TI - Effect of intraocular lens asphericity on posterior capsule opacification between two intraocular lenses with same acrylic material: a fellow-eye study. AB - PURPOSE: To evaluate intra-individual differences in posterior capsule opacification (PCO) and visual performance between spherical AcrySof SN60AT and an aspheric AcrySof SN60WF intraocular lens (IOL) with a posterior aspheric surface, both of which are made of same hydrophobic acrylic material. SETTING: Ophthalmology Department, St Thomas' Hospital, London, UK. METHODS: In this prospective randomized, fellow-eye comparison, an aspheric IOL, which is 9% thinner in comparison with the spherical IOL, was randomized to the first eye of 47 patients and fellow-eye surgery was performed within 3 weeks. Follow-up was at 1, 3, 6, 12 and 24 months. Corrected logMAR visual acuity (CDVA) was measured at 100% and 9% contrast. After pupil dilation, digital retroillumination photographs were taken and the mean PCO percentage was calculated using poco software at each follow-up visit. RESULTS: At 1, 3, 6, 12 and 24 months, 47 (94 eyes), 44 (88 eyes), 42 (84 eyes) and 41 (82 eyes) patients were followed-up respectively. Hundred per cent and 9% of LogMAR CDVA was not significantly different between the two IOLs (p = NS at all time-points). Percentage area PCO scores (mean +/- SD) at 1, 3, 6, 12 and 24 months with the spherical IOL was 5.82 +/- 9.89, 7.76 +/- 16.83, 7.21 +/- 12.46, 9.29 +/- 18.25 and 14.39 +/- 25.42, respectively, and with an aspheric IOL was 8.91 +/- 12.79, 5.97 +/- 10.32, 5.15 +/- 7.92, 7.68 +/- 11.18 and 12.18 +/- 20.10, respectively (p = NS at all time-points). CONCLUSIONS: Posterior capsule opacification was not significantly different between the spheric and aspheric IOLs in this fellow-eye, randomized comparison. Additional asphericity on the existing model of IOL does not influence PCO performance. PMID- 22067556 TI - Age and sex differences in the ventilatory response to hypoxia and hypercapnia in awake neonatal, pre-pubertal and young adult rats. AB - There is evidence for a "sensitive period" in respiratory development in rats around postnatal age (P) 12-13d. Little is known about sex differences during that time. The purpose of this study was to assess the effect of sex on breathing development, specifically around the "sensitive period". We used whole-body plethysmography to study breathing in normoxic, hypoxic and hypercapnic gases in non-anesthetized male and female neonatal rats from P10 to P15, juvenile (P30) and young adult (P90) rats. Compared to other neonatal ages, P12-13 male rats had significantly lower ventilation during normoxia, hypoxia, and hypercapnia. Compared to age-matched females, P12-13 male rats had lower ventilation in normoxia and hypoxia and a lower O(2) saturation during hypoxia. Circulating estradiol was greater in P12-13 male vs. female rats. Estradiol and ventilatory responses to hypoxia and hypercapnia were negatively correlated in neonatal male, but not female rats. Our results suggest that P10-15 includes a critical developmental period in male but not female rats. PMID- 22067558 TI - [Awake fibrecapnic intubation]. AB - Awake flexible intubation is the gold standard for difficult airway management but failures have been reported in up to 13% of cases. A novel technique called 'awake fibrecapnic intubation', developed in the Netherlands, is described here for the intubation of patients with head and neck cancer who have a difficult airway. After topical anaesthesia is administered, a flexible fibrescope is introduced into the pharynx. A special suction catheter is then advanced through the suction channel of this scope and then into the airway for the recording of carbon dioxide measurements. The catheter may also be used for oxygenation during the procedure. Spontaneous respiration is maintained in all patients. When four capnograms have been obtained, the flexible scope is railroaded over the catheter and after identification of tracheal rings or carina, the tracheal tube is placed. This new intubation technique is easier to learn than awake flexible intubation. PMID- 22067559 TI - [Cardiovascular polypill in high risk patients]. AB - The initial theoretical concept of a polypill was a fixed-dosed combination pill containing an antiplatelet agent, a cholesterol-lowering agent and multiple blood pressure-lowering agents aimed at the prevention of atherosclerotic vascular disease in the population aged 55 years and up. The reduction in the risk of cardiovascular disease does not depend on the cholesterol level and blood pressure at the start of treatment. The pharmacological reduction in risk factors in individuals with a high risk of atherosclerotic vascular disease is often suboptimal, partly due to the complexity of the guidelines and low adherence to the therapy. A polypill may offer opportunities for improvement. Research has shown that the use of combination products leads to a greater reduction in risk factors than the use of separate substances, possibly through improved adherence to the therapy. The use of a polypill in the prevention of vascular disease in high-risk patients may lead to a more effective reduction in risk, a decrease in costs and a reduction in pharmacological expenditure. PMID- 22067560 TI - [Intestinal ischaemia caused by acute mesenteric vein thrombosis]. AB - Acute mesenteric vein thrombosis is an uncommon cause of intestinal ischaemia, with a considerable morbidity and mortality rate. There is a delay in diagnosis owing to the fact that patients present with non-specific abdominal symptoms; there is often a low level of suspicion by the clinician. We discuss the case histories of a 23 year-old woman and a 49 year-old woman with intestinal ischaemia caused by acute mesenteric vein thrombosis. These patients presented at two different hospital emergency departments. In patients with acute, progressive abdominal complaints, mesenteric vein thrombosis must be included in the differential diagnosis, especially if there are thromboembolic risk factors. In such patients, CT angiography (CTA) must be performed during the arterial and portal-venous phase to evaluate the mesenteric circulation. PMID- 22067561 TI - [Cholecystectomy without visible scars: the transvaginal method]. AB - Since the 1990's, laparoscopic cholecystectomy has been the standard procedure for symptomatic gallstone disease. Natural Orifice Transluminal Endoscopic Surgery (NOTES) is the next logical step in the development of minimal invasive surgery. During a NOTES procedure, a natural orifice is used to gain access to the abdominal cavity instead of incisions through the abdominal wall. In this article we report the introduction of the NOTES technique to the Netherlands. In our institution, 15 women with gallstone disease recently underwent transvaginal cholecystectomy. The procedure performed was a hybrid NOTES cholecystectomy. Only one trocar was inserted through the umbilicus, and two other instruments were inserted through the vagina. The potential advantages of this technique include a better cosmetic result and less postoperative pain. The number and type of complications do not appear to differ from those of the standard laparoscopic cholecystectomy. PMID- 22067562 TI - [Primary torsion of the omentum majus]. AB - BACKGROUND: Primary torsion of the omentum majus is a rare condition. The clinical picture can mimic other causes of acute abdominal pain. The condition is therefore often not recognised and the diagnosis is made only perioperatively. CASE DESCRIPTION: A 32-year-old man visited the emergency department with acute abdominal pain. During surgery, the pain turned out to be caused by an ischaemic segment of the omentum majus, resulting in torsion. In retrospect, the patient had been suffering from recurrent attacks of similar abdominal pain for years without a satisfactory diagnosis. CONCLUSION: In any patient with episodes of recurrent, localised, stabbing abdominal pain, possibly related to exercise and without any other clear diagnosis, the diagnosis 'torsion of the omentum majus' should be considered. PMID- 22067563 TI - Maintenance of primary tumor phenotype and genotype in glioblastoma stem cells. AB - The clinicopathological heterogeneity of glioblastoma (GBM) and the various genetic and phenotypic subtypes in GBM stem cells (GSCs) are well described. However, the relationship between GSCs and the corresponding primary tumor from which they were isolated is poorly understood. We have established GSC-enriched neurosphere cultures from 15 newly diagnosed GBM specimens and examined the relationship between the histopathological and genomic features of GSC-derived orthotopic xenografts and those of the respective patient tumors. GSC-initiated xenografts recapitulate the distinctive cytological hallmarks and diverse histological variants associated with the corresponding patient GBM, including giant cell and gemistocytic GBM, and primitive neuroectodermal tumor (PNET)-like components. This indicates that GSCs generate tumors that preserve patient specific disease phenotypes. The majority of GSC-derived intracerebral xenografts (11 of 15) demonstrated a highly invasive behavior crossing the midline, whereas the remainder formed discrete nodular and vascular masses. In some cases, GSC invasiveness correlated with preoperative MRI, but not with the status of PI3 kinase/Akt pathways or O(6)-methylguanine methyltransferase expression. Genome wide screening by array comparative genomic hybridization and fluorescence in situ hybridization revealed that GSCs harbor unique genetic copy number aberrations. GSCs acquiring amplifications of the myc family genes represent only a minority of tumor cells within the original patient tumors. Thus, GSCs are a genetically distinct subpopulation of neoplastic cells within a GBM. These studies highlight the value of GSCs for preclinical modeling of clinically relevant, patient-specific GBM and, thus, pave the way for testing novel anti GSC/GBM agents for personalized therapy. PMID- 22067564 TI - A new level of spindle assembly checkpoint inactivation that functions without mitotic spindles. PMID- 22067566 TI - Holding the line. AB - When problems occur in healthcare nurses are often blamed. Press and public may consider that the nurse should have done more or that nurses should have spoken out. Do problems occur because of staff who are not fit to be nurses, or is the situation more complex? PMID- 22067565 TI - Inotropic support in the NICU: ever more compounds in search of guidance? Commentary on J. Esch et al.: differential hemodynamic effects of levosimendan in a porcine model of neonatal hypoxia-reoxygenation (Neonatology 2012;101:192-200) and M.P. De Carolis et al.: levosimendan in two neonates with ischemic heart failure and pulmonary hypertension (Neonatology 2012;101:201-205). PMID- 22067567 TI - End-of-life care in the community: attaining a critical balance. AB - There are not many people who will argue against the need for high-quality care in all healthcare settings, and particularly at the end of life. The recently published report by the Care Quality Commission (CQC, 2011) makes a number of negative observations about poor quality of care in the 100 hospitals they inspected. The report concluded that many hospitals are failing to meet basic needs of older people. It is important that we nurses provide essential care, as there is nothing basic about patients' needs, wishes and aspirations at the end of their lives. PMID- 22067568 TI - Catheterization in the community: converting to the Foley catheter tray. AB - With the aim of minimizing clinical incidents and improving clinical practice, the Cardiff and Vale University Health Board carried out a trial of a Foley catheter tray to be carried by district nurses as emergency boot stock. As part of the trial all nurses had to undergo training on the Foley catheter tray prior to use. The district nurses using the tray reported improvement in confidence, efficiency, convenience and patient experience. Owing to the success of the initiative, use of the Foley catheter tray as emergency boot stock is now standard practice for District Nursing/Acute Response and out-of-hours care in the Cardiff and Vale area. PMID- 22067569 TI - Using FRAX to assess the risk that an older person will suffer a fragility fracture. AB - A challenge of planning for local health services is how to prevent the effects of diseases of older age in order to reduce individual suffering and also wider economic costs to society. This article discusses FRAX(r) (Fracture Risk Assessment), a computer-based algorithm that allows 10-year probability of a hip and osteoporotic fracture calculation in people aged 40-90 years. The inclusion of FRAX within the portfolio of risk assessment measures available to community nurses is recommended to aid identification and referral of clients at risk of fragility fractures. PMID- 22067570 TI - Meeting the policy agenda, part 2: is a 'Cinderella service' sufficient? AB - This is the second of two papers that examine district nursing within a changing health policy and service environment. The first paper explored the current UK policy context and the way in which district nursing and community nursing services within each country are changing to meet the challenges posed. This article considers the current district nurse (DN) role, which has constantly evolved over the past 150 years, and considers the educational framework that underpins the preparation of these specialist community practitioners in relation to community colleagues such as specialist community public health nurses (SCPHNs). In the context of the current economic climate, there is concern that the apprenticeship model of staff development is replacing specialist practitioner education for DNs, solely on the basis of resource. This article explores the current challenges for DN education within the UK. The underpinning educational preparation of DN programmes is examined and key issues such as safeguarding the public are discussed. The need to develop a cohesive approach to education for post-qualification nurses in the community is advocated. These are important considerations for the future of a discipline which currently feels under threat. PMID- 22067571 TI - Spirituality in end-of-life care: attending the person on their journey. AB - Spirituality is a fundamental element to the human experience of health and healing, illness and dying. Spiritual care is an essential component of palliative and end-of-life care provision and is the responsibility of all staff and carers involved in the care of patients and families. As end-of-life care is a significant element of community nursing, this article explores the relevancy of spirituality to end-of-life practice, the challenge of defining spirituality and the attributes and skills required for the practice of spiritual care. The aim of is to encourage self reflection and open dialogue about the subject, thus enhancing community nurses' understanding of spiritual care practice. By reflecting and generating talk about the practice of spiritual care, it may become more normalized, recognized, and practically meaningful, thereby retaining its significance in holistic nursing. PMID- 22067572 TI - Transforming the UK's response to HIV: addressing AIDS in the community. AB - HIV (human immunodeficiency virus) is a serious public health issue in UK. More than 90000 people are currently living with HIV and a full quarter of these people are not aware that they have it. Further, there are 6000-7000 new HIV diagnoses every year. PMID- 22067573 TI - A process for developing a principle-centred district nursing service philosophy. AB - While it is well known that team vision and values statements in nursing can promote person-centred care, practitioner role clarity and empowerment, and service effectiveness, especially during times of change, their use in district nursing is limited. Accepted practice is to formulate vision and values statements 'from the top', and then seek buy-in from other staff groups, however, this inhibits practitioner engagement. This paper describes the use of group facilitation, based on principle-centred leadership practices, to engage practitioners in all the creative aspects of developing a values statement. Increasing practitioner engagement would be expected to provide the above benefits by improving communication with service-users and other key stakeholders and by motivating performance evaluation and improvement. PMID- 22067574 TI - Prescription of controlled drugs by non-medical prescribers. AB - The Government has again promised to end the confusion over the range and use of controlled drugs by non-medical prescribers (NMPs). A recent written answer suggests that regulations allowing district nurses who are NMPs to prescribe the full range of controlled drugs will be in place by the end of October 2011. This is the third time successive governments have made such a commitment, and until it is confirmed district nurses who are independent nurse prescribers must limit their use of controlled drugs to those set out in the British National Formulary and Drug Tariff. This article sets out the limitations on an independent nurse prescriber's right to prescribe controlled drugs under current legislation. PMID- 22067575 TI - What's happening to nursing? AB - This year has been remarkable for the negative media reporting of nursing and nurses. First, the Health Service Ombudsman (2011) highlighted the deficiencies of care relating to ten older people who as a consequence experienced unnecessary pain, distress and indignity which cast a long shadow over their families. PMID- 22067577 TI - Television viewing and variations in energy intake in adults and children in the USA. AB - OBJECTIVE: Examine the association between energy intake and television (TV) viewing in Americans. DESIGN: Nationally representative, cross-sectional study of 2003-2006 National Health and Nutrition Examination Survey. SETTING: Total energy intake was determined by two 24 h recalls. TV viewing was reported as low (<=1 h/d), middle (2-3 h/d), and high (>=4 h/d). Multivariate linear regression models were used to analyse TV viewing and energy intake, adjusted for BMI (percentile for children 2-18 years), age, ethnicity and physical activity. SUBJECTS: Pre school children (2-5 years; n 1369), school-age children (6-11 years; n 1759), adolescents (12-18 years; n 3233) and adults (>=19 years; n 7850) in the USA. RESULTS: There was a significant association between TV viewing and energy intake for adolescent girls (high v. low: beta = 195.2, P = 0.03) and men (high v. low: beta = -113.0, P = 0.02; middle v. low: beta = -131.1, P = 0.0002). Mean adjusted energy intake for adolescent girls was 7801.0, 8088.5 and 8618.2 kJ/d for low, middle and high TV viewing, respectively. Mean adjusted energy intake for men was 9845.9, 9297.2 and 9372.8 kJ/d for low, middle and high TV viewing. CONCLUSIONS: TV viewing was associated with energy intake in US children and adults only in 12 18-year-old girls and men. For girls, the high TV viewing category consumed more energy daily (816.3 kJ (195 kcal)) than the low category. In men, the middle and high TV viewing categories consumed less energy daily (548.4 kJ (131 kcal) and 473.0 kJ (113 kcal), respectively) than the low category. Our findings support some, but not all previous research. Future research is needed to explore this complicated relationship with rigorous measures of energy intake and TV viewing. PMID- 22067578 TI - Ethnobotanical investigation of 'wild' food plants used by rice farmers in Kalasin, Northeast Thailand. AB - BACKGROUND: Wild food plants are a critical component in the subsistence system of rice farmers in Northeast Thailand. One of the important characteristics of wild plant foods among farming households is that the main collection locations are increasingly from anthropogenic ecosystems such as agricultural areas rather than pristine ecosystems. This paper provides selected results from a study of wild food conducted in several villages in Northeast Thailand. A complete botanical inventory of wild food plants from these communities and surrounding areas is provided including their diversity of growth forms, the different anthropogenic locations were these species grow and the multiplicity of uses they have. METHODS: Data was collected using focus groups and key informant interviews with women locally recognized as knowledgeable about contemporarily gathered plants. Plant species were identified by local taxonomists. RESULTS: A total of 87 wild food plants, belonging to 47 families were reported, mainly trees, herbs (terrestrial and aquatic) and climbers. Rice fields constitute the most important growth location where 70% of the plants are found, followed by secondary woody areas and home gardens. The majority of species (80%) can be found in multiple growth locations, which is partly explained by villagers moving selected species from one place to another and engaging in different degrees of management. Wild food plants have multiple edible parts varying from reproductive structures to vegetative organs. More than two thirds of species are reported as having diverse additional uses and more than half of them are also regarded as medicine. CONCLUSIONS: This study shows the remarkable importance of anthropogenic areas in providing wild food plants. This is reflected in the great diversity of species found, contributing to the food and nutritional security of rice farmers in Northeast Thailand. PMID- 22067580 TI - Keeping patients safe: protecting this priority. PMID- 22067579 TI - Impact of intraperitoneal chemotherapy after gastrectomy with positive cytological findings in peritoneal washings. AB - BACKGROUND: There is no standard treatment available for gastric cancer patients whose sole 'non-curative factor' is positivecytological findings in peritoneal washings (CFPW). The aim of this study was to examine the safety, pharmacokinetics and efficacy for free intraperitoneal cancer cells of intraperitoneal chemotherapy with paclitaxel after gastrectomy with en bloc D2 lymph node dissection in cases of gastric cancer with positive CFPW. METHODS: Ten patients with gastric cancer who underwent gastrectomy and systemic lymphadenectomy with D2 dissection, without any other non-curative factors besides positive CFPW, were treated with early postoperative intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complications were measured using NCI-CTC version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatographic assay. RESULTS: Grade 3/4 toxic effects included anemia (20%) and neutropenia (10%) that required no treatment. Operative complications were, for example, superficial surgical site infections (10%) that were treated with antibiotics. No viable cancer cells were observed in the intra-abdominal fluid 24 h after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve ratio was 2,003.3:1. CONCLUSION: Intraperitoneal chemotherapy with paclitaxel is a safe and effective treatment modality for free intraperitoneal cancer cells. PMID- 22067581 TI - Perfect victims: protecting vulnerable adults. PMID- 22067582 TI - Patient safety and healthcare-associated infection. AB - Healthcare-associated infection (HCAI) has become a major patient safety issue in National Health Service (NHS) hospitals. The UK has an HCAI prevalence rate of 8.2% which equates to an annual incidence of approximately 300000 patients (Hospital Infection Society, 2007). HCAI is a safety issue because it is associated with increased morbidity and mortality as well as increased healthcare costs (National Audit Office (NAO), 2009). In 2000, the NAO identified cultural change as a requirement if the NHS is to get a grip of infection prevention and control. This article has taken a 'conceptual culture of safety model' that has been previously described in the literature and applied it to the organization of infection control. It is clear that while there are many areas of good practice, in relation to infection prevention and control, there is still much to do if the NHS is to invoke the type of paradigm shift that will result in a mature sustainable safety culture. PMID- 22067583 TI - Tuberculosis and infection control. AB - Against a background of rising tuberculosis (TB) rates, increasing incidence of TB and human immunodeficiency virus (HIV) co-infection, coupled with the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), the need for effective TB infection control has never been more vital (World Health Organization (WHO), 2009). TB infection control has been defined as 'a combination of measures aimed at minimizing the risk of TB transmission within populations' (WHO, 2009: p.ix). Health professionals are frequently confused about appropriate infection control measures when caring for patients affected by infectious respiratory tuberculosis (Mohandas and Cunniffe, 2009). This article aims to address the key infection control measures required to optimize patient care and reduce the risk of TB transmission within hospital and community settings. PMID- 22067584 TI - Sexual dysfunction in rheumatoid arthritis: a hot but sensitive issue. AB - Rheumatoid arthritis (RA) has considerable personal impact for sufferers and their families. Those with RA suffer from pain, restricted joint movements, and fatigue, and can have problems with self-esteem and body image. It is also possible that medication causes sexual problems. Research on the subject is limited, and shows a divergent picture. Assessment for sexual dysfunction in clinical practice might be another hurdle, as patients and health professionals are reluctant to discuss this issue face to face. The aim of the work carried out and described in this article was to study the possibility of implementing sexual dysfunction assessment into standard rheumatology clinical practice. Results revealed that the multidimensional patient-reported outcome measures questionnaire offered the opportunity to assess the disease activity parameters, functional disability, quality of life, sexual dysfunction, and self-helplessness in one format. The patients appeared willing to complete questionnaires and this may be an acceptable tool for assessment. Improving patient education, as well as nurse-patient communication, through discussions about available options may minimize patients' feelings of isolation in addressing the problem and could help compensate for negative effects resulting from the disease. PMID- 22067585 TI - Supporting self and others: from staff nurse to nurse consultant. Part 9: solution-focused support. PMID- 22067586 TI - The snapshot pre-registration assessment tool. Part 1: background, literature and research. AB - This is the first of a two-part article that presents a new assessment tool - the snapshot - for pre-registration nurses in clinical practice, that is being used at Kingston University/St George's University of London during year 3 of the Diploma and BSc programmes. A pilot study of the use of the snapshot in a simulation environment had previously been undertaken and as a result of this, the snapshot was piloted as part of continuous clinical assessment in practice on two cohorts of third-year pre-registration student nurses. An evaluative study was undertaken. This article describes the background to the project, the literature and the research methods used to undertake the evaluative research study. Part 2 will focus on the findings and a discussion of these findings mapped against the literature. PMID- 22067588 TI - Regulating support workers: is the Government listening? PMID- 22067587 TI - The future of nurse training: can unsuitable students be identified? PMID- 22067589 TI - When health professionals cause harm to patients. PMID- 22067590 TI - Prejudice in nursing appointments 100 years ago. PMID- 22067591 TI - Practice makes perfect. PMID- 22067592 TI - Acute infarct of the corpus callosum presenting as alien hand syndrome: evidence of diffusion weighted imaging and magnetic resonance angiography. AB - BACKGROUND: Infarcts of the corpus callosum are rare and have not been well documented previously. As for a variety of signs and symptoms presented, alien hand syndrome (AHS) can be easily overlooked. CASE PRESENTATION: In this report, we present a patient with a mixed types of AHS coexistence secondary to the corpus callosum infarction, including a motor type of AHS by intermanual conflict (callosal type AHS) and a sensory type of AHS by alien hand and left hemianesthesia (posterior AHS). CONCLUSIONS: Our case may contribute to the early recognition of AHS and to explore the abnormal neural mechanism of AHS. To our knowledge, rare reports have ever documented such mixed AHS coexisting secondary to the callosal lesion, based on advanced neuroimaging methods as in our case. PMID- 22067593 TI - The winding road from research to practice through theory. PMID- 22067594 TI - Perceived family functioning and suicidal ideation: hopelessness as mediator or moderator. AB - BACKGROUND: : Suicidal ideation has been identified increasingly as a problem among university students in Hong Kong. Understanding the relationships among hopelessness, perceived family functioning, and suicidal ideation is essential to designing effective interventions. OBJECTIVES: : The aims of this study are to explore the relationships among hopelessness, perceived family functioning, and suicidal ideation and to examine the moderating and mediating roles played by hopelessness on suicidal ideation. METHODS: : A cross-sectional survey using convenience sampling was conducted. A questionnaire was administered to 350 university students with ages 18 to 25 years. The questions measured levels of suicidal ideation, perceived family functioning, and hopelessness of the students. Data analyses, including correlation and multiple hierarchical regression analyses, were conducted to examine the mediating and moderating roles of hopelessness on suicidal ideation. RESULTS: : Perceived family functioning (B = -.10, p < .05) and hopelessness (B = .56, p < .001) were shown to be significant predictors of suicidal ideation. Hopelessness was found to mediate only partially but moderate the impact of perceived family functioning on suicidal ideation (B = -.88, p < .05), hence expanding Beck's cognitive theory of suicide. CONCLUSION: : Perceived family functioning and hopelessness are significant predictors, whereas hopelessness is a partial mediator and a significant moderator of suicidal ideation. Therefore, interventions that enhance family functioning and lower the sense of hopelessness may be effective in decreasing suicidal ideation among university students. PMID- 22067595 TI - Pilot study: individualized training for caregivers of hospitalized older veterans. AB - BACKGROUND: : The hospital-to-home transition represents a vulnerable time for older veterans who are more medically and socioeconomically challenged than the general population of older adults. OBJECTIVES: : The aim of this study was examine the feasibility of delivering an individualized caregiver training program before hospital discharge of older veterans. As an exploratory aim, the impact of this training on caregiver self-efficacy and preparedness was determined. METHODS: : The sample consisted 50 caregiver-patient dyads. Training included medication management, identification of medical red flags, identification of Veterans Affairs community-based resources, and specific caregiver concerns about home care. Program feasibility was determined by whether caregivers could be recruited and could complete the training before patients were discharged from the hospital. Caregiver self-efficacy (using modified Lorig's self-efficacy scale) and preparedness (using Preparedness in Caregiving Scale) were assessed before the training (T1), immediately after the training (T2), and 1 week (T3) and 4 weeks (T4) after hospital discharge. RESULTS: : One thousand six hundred ninety inpatients were screened, 252 of whom (15%) met study eligibility criteria. Of these, 112 were approached, and 50 dyads (44.6%) agreed to participate. Of the 50 consented dyads, 40 caregivers (80%) received the training. The mean self-efficacy among caregivers improved at T2, and the improvement was sustained at T3 and T4 (T1, 783.86; T2, 903.64; T3, 867.85; T4, 877.02). The same trend was observed in caregiving preparedness (T1, 26. 95; T2, 30.55; T3, 28.88; T4, 28.91). DISCUSSION: : Providing an individualized training program to informal caregivers of hospitalized older veterans was not only feasible but was also associated with increased self-efficacy and caregiving preparedness. This study has the potential to assist caregivers in their home care of older veterans after hospital discharge. PMID- 22067596 TI - Decreased heart rate variability during emotion regulation in subjects at risk for psychopathology. AB - BACKGROUND: Dysfunctions in the regulation of emotional responses are related to poor psychological well-being and increased impact of cardiovascular disease. It has been suggested that the relationship between negative affect and higher morbidity could be mediated by a dysregulation of the autonomic nervous system (ANS), for example, of heart rate variability (HRV). Neuroticism is a personality trait associated with a maladaptive emotion regulation and also with alterations in ANS function. However, it is unknown whether subjects with high neuroticism present with specific biases in emotion regulation associated with reduced HRV. METHOD: In total, 33 healthy subjects (n=13, highly neurotic) performed an emotion regulation task, during which they were instructed to either passively view negative pictures or attempt to down-regulate the affect elicited by the images. During the task an electrocardiogram was recorded and HRV was measured by calculation of the high frequency spectrum (HF-HRV). RESULTS: A significant interaction between task condition and personality group was observed on HF-HRV measures (F 1,31=6.569, p=0.016). This was driven by subjects with low neuroticism presenting higher HF-HRV during down-regulation compared to passive exposure to negative stimuli, while subjects with high neuroticism reported an opposite tendency. CONCLUSIONS: Our results show reduced HF-HRV during cognitive reappraisal of negative stimuli in high neuroticism and indicate a specific link between loss of flexibility in the parasympathetic cardiovascular tone and emotion regulation, consistent with previous work. Such findings support the importance of exploring the combination of ANS adaptability and emotional dysregulation in neuroticism as different facets of a common psychosomatic vulnerability factor. PMID- 22067597 TI - Hydrogen induced changes in the crystal structure and magnetic properties of UCoGe. AB - Hydrogen pressure of 0.5-140 bar has been applied to synthesize hydrides of UCoGe. Besides an alpha hydride crystallizing in the structure type of the parent compound, which loses the weak ferromagnetism found in pure UCoGe, two distinctly different beta hydrides were identified. The almost pure beta hydride (UCoGeH(1.7)) is a ferromagnet below T(C) = 50 K. The highest H(2) pressures (> 130 bar) produce admixture of another hydride called beta' hydride, with less H/f.u. and T(C) = 8 K, obtained presumably as a decay product of a full hydride UCoGeH(2.0) unstable at ambient conditions. The value of the Sommerfeld coefficient of electronic specific heat gamma increases over 100 mJ mol(-1) K(-2) for the magnetic hydrides. PMID- 22067598 TI - Brain arginine vasotocin immunoreactivity differs between urban and desert curve billed thrashers, Toxostoma curvirostre: relationships with territoriality and stress physiology. AB - The neuropeptide arginine vasotocin (AVT: the avian homolog of vasopressin) has numerous functional roles including mediating social behaviors, coregulating the adrenocortical stress response and maintaining water balance. These functions of AVT make it susceptible to environmental influence, yet little is understood concerning the variation in the AVT system across habitats. In this study, AVT immunoreactivity was compared between male curve-billed thrashers, Toxostoma curvirostre, from native Sonoran Desert locations and those within the city of Phoenix, Ariz. Previous research found that urban thrashers are more responsive to territorial intrusion, secrete more corticosterone (CORT) during capture stress, and they may also have greater access to water than desert counterparts. Variation in AVT immunoreactivity was also related to levels of plasma CORT and osmolality, and with behavioral responses to a simulated territorial intrusion. Birds from these two habitats showed different AVT immunoreactive patterns in two brain regions: the paraventricular nucleus of the hypothalamus and the medial bed nucleus of the stria terminalis (BSTM), a part of the limbic system. Immunoreactive AVT within the paraventricular nucleus was associated with plasma CORT levels in urban, but not desert, birds, but no such association with osmolality was observed in birds from either habitat. The total number of BSTM AVT-immunoreactive cells was related to a decreased responsiveness to territorial intrusion. These data suggest that divergence in the AVT system between urban and desert thrashers may help explain observed differences in both the adrenocortical stress response and territorial behavior between populations. Whether differences in water availability between habitats contribute to population differences in the brain AVT system is unknown. PMID- 22067599 TI - Controlled hydrostatic sinus elevation: a novel method of elevating the sinus membrane. AB - Maxillary sinus elevation surgery has been practiced successfully over the past several decades with good outcomes, but tears and perforations still occur in significant numbers. The presumed cause of these problems is the fact that all methods currently used place "point sources" of lifting pressure on the Schneiderian membrane. A new procedure, controlled hydrostatic sinus lift, is presented herein as a safer, more controlled "lifting pressure" which simultaneously places equal force per square millimeter of bone-membrane interface. Hydraulic pressure in a closed system places equal pressure on all surfaces within the system, thereby eliminating "point sources" of pressure and gently elevating the Schneiderian membrane equally at all points of attachment. This controlled hydrostatic sinus lift procedure is accomplished by using a calibrated, hand-controlled pump and in-line pressure sensor meter. PMID- 22067600 TI - Maxillary sinus floor augmentation using bovine bone grafts with simultaneous implant placement: a 5-year prospective follow-up study. AB - PURPOSE: The aim of this study was to evaluate the 5 year clinical results of maxillary sinus floor augmentation using bovine bone grafts with simultaneous implant placement. MATERIAL AND METHODS: A total of 28 patients were enrolled in the study, and a total of 84 implants were placed into the grafted sites. Unilateral or bilateral sinus augmentation was performed, and implants were inserted into the augmented sinuses. After osseointegration and insertion of the prosthesis, the implants were evaluated by clinical and radiographic parameters. RESULTS: The cumulative implant survival rate after 60 months of loading was 100%. Periimplant bone loss was at clinically acceptable levels (0.146 and 0.34 mm after 1 and 5 years, respectively). CONCLUSIONS: Bovine bone grafts used in 1 stage sinus augmentation yields sufficient quality and volume of bone for predictable simultaneous implant placement. PMID- 22067601 TI - Clinical study of graft materials using autogenous teeth in maxillary sinus augmentation. AB - PURPOSE: The purpose of this study was to evaluate the effectiveness of autogenous tooth bone graft materials. MATERIALS AND METHODS: Hundred implants in 51 patients were selected, and the patients received maxillary sinus augmentation and implant placement using autogenous tooth graft materials at the Chosun University Dental Hospital and Seoul National University Bundang Hospital between July 2009 and November 2010. RESULTS: In cases using autogenous tooth bone graft alone, or together with other graft material, the implant survival rate was 96.15%. On histomorphologic examination, autogenous tooth bone graft materials showed gradual resorption and new bone formation through osteoconduction and osteoinduction. CONCLUSIONS: The results indicated that autogenous tooth bone graft materials are appropriate for use in maxillary sinus augmentation. PMID- 22067602 TI - Flapless approach to maxillary sinus augmentation using minimally invasive antral membrane balloon elevation. AB - In the atrophic posterior maxilla, successful implant placement is often complicated by the lack of quality and volume of available bone. In these cases, sinus floor augmentation is recommended to gain sufficient bone around the implants. Sinus elevation can be performed by either an open lateral window approach or by a closed osteotome approach depending on available bone height. This case series demonstrates the feasibility and safety of minimally invasive antral membrane balloon elevation, followed by bone augmentation and implant fixation in 20 patients with a residual bone height of 2 to 6 mm below the sinus floor. The surgical procedure was performed using a flapless approach. At 18 months follow-up, the implant survival rate was 100%. Absence of patient morbidity and satisfactory bone augmentation with this minimally invasive procedure suggests that minimally invasive antral membrane balloon elevation should be considered as an alternative to some of the currently used methods of maxillary bone augmentation. PMID- 22067604 TI - Surface edges mitigate the disparity gradient constraint on binocular fusion and visual direction. AB - One function of the visual system is to combine the different views of the two eyes so that each object appears in a single direction. Using pairs of isolated dots, previous studies have found that binocular fusion gives way to diplopia if the disparity gradient between the dots is steep. This paper evaluates whether fusion is possible in the presence of steep disparity gradients if those gradients occur between the edges of two surfaces, not isolated dots. Two target squares with a steep disparity gradient were presented alone, or were incorporated into separate surfaces - one foreground, the other background. The addition of surfaces, or support texture, restored fusion, overcoming the disparity gradient constraint on fusion. Visual direction was the average of the monocular views in the presence of support texture, indicating that single vision arose from fusion rather than a local suppression of one eye's view. The results suggest a close relationship between the disparity gradient constraint on fusion and the mitigating influence of support texture, because both effects decline dramatically over the same small range of element separations and both effects are reduced by differences in contrast polarity. PMID- 22067605 TI - The role of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphomas. AB - Extracorporeal photochemotherapy (ECP) is an effective treatment modality for patients with erythrodermic myocosis fungoides (MF) and Sezary syndrome (SS). During ECP, a fraction of peripheral blood mononuclear cells is collected, incubated ex-vivo with methoxypsoralen, UVA irradiated, and finally reinfused to the patient. Although the mechanism of action of ECP is not well established, clinical and laboratory observations support the hypothesis of a vaccination-like effect. ECP induces apoptosis of normal and neoplastic lymphocytes, while enhancing differentiation of monocytes towards immature dendritic cells (imDCs), followed by engulfment of apoptotic bodies. After reinfusion, imDCs undergo maturation and antigenic peptides from the neoplastic cells are expressed on the surface of DCs. Mature DCs travel to lymph nodes and activate cytotoxic T-cell clones with specificity against tumor antigens. Disease control is mediated through cytotoxic T-lymphocytes with tumor specificity. The efficacy and excellent safety profile of ECP has been shown in a large number of retrospective trials. Previous studies showed that monotherapy with ECP produces an overall response rate of approximately 60%, while clinical data support that ECP is much more effective when combined with other immune modulating agents such as interferons or retinoids, or when used as consolidation treatment after total skin electron beam irradiation. However, only a proportion of patients actually respond to ECP and parameters predictive of response need to be discovered. A patient with a high probability of response to ECP must fulfill all of the following criteria: (1) SS or erythrodermic MF, (2) presence of neoplastic cells in peripheral blood, and (3) early disease onset. Despite the fact that ECP has been established as a standard treatment modality, no prospective randomized study has been conducted so far, to the authors' knowledge. Considering the high cost of the procedure, the role of ECP in the treatment of SS/MF needs to be clarified via well designed multicenter prospective randomized trials. PMID- 22067606 TI - Large-scale use of mosquito larval source management for malaria control in Africa: a cost analysis. AB - BACKGROUND: At present, large-scale use of two malaria vector control methods, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) is being scaled up in Africa with substantial funding from donors. A third vector control method, larval source management (LSM), has been historically very successful and is today widely used for mosquito control globally, except in Africa. With increasing risk of insecticide resistance and a shift to more exophilic vectors, LSM is now under re-evaluation for use against afro-tropical vector species. Here the costs of this intervention were evaluated. METHODS: The 'ingredients approach' was used to estimate the economic and financial costs per person protected per year (pppy) for large-scale LSM using microbial larvicides in three ecologically diverse settings: (1) the coastal metropolitan area of Dar es Salaam in Tanzania, (2) a highly populated Kenyan highland area (Vihiga District), and (3) a lakeside setting in rural western Kenya (Mbita Division). Two scenarios were examined to investigate the cost implications of using alternative product formulations. Sensitivity analyses on product prices were carried out. RESULTS: The results show that for programmes using the same granular formulation larviciding costs the least pppy in Dar es Salaam (US$0.94), approximately 60% more in Vihiga District (US$1.50) and the most in Mbita Division (US$2.50). However, these costs are reduced substantially if an alternative water-dispensable formulation is used; in Vihiga, this would reduce costs to US$0.79 and, in Mbita Division, to US$1.94. Larvicide and staff salary costs each accounted for approximately a third of the total economic costs per year. The cost pppy depends mainly on: (1) the type of formulation required for treating different aquatic habitats, (2) the human population density relative to the density of aquatic habitats and (3) the potential to target the intervention in space and/or time. CONCLUSION: Costs for LSM compare favourably with costs for IRS and LLINs, especially in areas with moderate and focal malaria transmission where mosquito larval habitats are accessible and well defined. LSM presents an attractive tool to be integrated in ongoing malaria control effort in such settings. Further data on the epidemiological health impact of larviciding is required to establish cost effectiveness. PMID- 22067607 TI - Intravitreous interleukin-2 treatment and inflammation modulates glial cells activation and uncrossed retinotectal development. AB - Interleukin-2 (IL-2) plays regulatory functions both in immune and nervous system. However, in the visual system, little is known about the cellular types which respond to IL-2 and its effects. Herein, we investigated the influence of IL-2 in the development of central visual pathways. Lister Hooded rats were submitted to multiple (at postnatal days [PND]7/10/13) or single (at PND10) intravitreous injections of phosphate-buffered saline (PBS) (vehicle), zymosan, or IL-2. IL-2 receptor alpha subunit was detected in the whole postnatal retina. Chronic treatment with either PBS or IL-2 increases retinal glial fibrillary acidic protein (GFAP) expression, induces intravitreous inflammation revealed by the presence of macrophages, and results in a slight rearrangement of retinotectal axons. Acute zymosan treatment disrupts retinotectal axons distribution, confirming the influence of inflammation on retinotectal pathway reordering. Furthermore, acute IL-2 treatment increases GFAP expression in the retina without inflammation and produces a robust sprouting of the intact uncrossed retinotectal pathway. No difference was observed in glial cells activity in superior colliculus. Taken together, these data suggest that inflammation and interleukin-2 modulate retinal ganglion cells development and the distribution of their axons within central targets. PMID- 22067608 TI - The vertebrate homolog of sulfide-quinone reductase is expressed in mitochondria of neuronal tissues. AB - Hydrogen sulfide (H2S) can be consumed by both invertebrates and vertebrates as an inorganic substrate. The pathway metabolizing H2S probably involves three mitochondrial enzymes, one of which is sulfide-quinone oxidoreductase (SQR), known as sulfide-quinone reductase-like protein (SQRDL) in vertebrates. Evidence from fission yeast suggests that SQR might have a role in regulating sulfide levels in the cell. Regulation might be essential for H2S to act as a gaseous transmitter (gasotransmitter). The brain is an organ with high activity of gasotransmitters, like nitric oxide (NO) and H2S, which are known to affect synaptic transmission. In this study, we provide evidence that SQRDL is expressed in the mammalian brain. Real-time polymerase chain reaction (PCR) showed an increase in the number of Sqrdl transcripts in the brain with increasing age. Cellular fractionation and subsequent analysis by Western blotting indicated that the protein is located in mitochondria, which is the site of sulfide consumption in the cell. With an immunohistochemical approach, we demonstrated that the SQRDL protein is expressed in neurons, oligodendrocytes, and endothelial cells. Taken together, our data suggest that brain tissue harbors the machinery required for local regulation of sulfide levels. PMID- 22067609 TI - Memory impairment induced by brain iron overload is accompanied by reduced H3K9 acetylation and ameliorated by sodium butyrate. AB - Iron accumulation in the brain has been associated to the pathogenesis of neurodegenerative disorders. We have previously demonstrated that iron overload in the neonatal period results in severe and persistent memory deficits in adult rats. Alterations in histone acetylation have been associated with memory deficits in models of neurological disorders. Here we examine histone acetylation in the brain and the effects of the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) on memory in the neonatal iron overload model in rats. Rats received vehicle or 30.0-mg/kg Fe+2 orally at postnatal days 12-14. When animals reached adulthood, they were given training in either novel object recognition or inhibitory avoidance. Histone acetylation in the dorsal hippocampus and the effects of NaB were examined in separate sets of rats. Iron overload led to a reduction in H3 lysine 9 acetylation in the hippocampus, without affecting the acetylation of other H3 and H4 lysine residues. A single systemic injection of NaB (1.2 g/kg) immediately after training ameliorated iron-induced memory impairments. The results suggest that a reduction in H3K9 acetylation might play a role in iron-induced memory impairment and support the view that HDACis can rescue memory dysfunction in models of brain disorders. PMID- 22067610 TI - BMPR1A is a candidate gene for congenital heart defects associated with the recurrent 10q22q23 deletion syndrome. AB - Congenital heart defects (CHD) are associated with the recurrent 10q22q23 deletion syndrome and with partially overlapping distal 10q23.2.q23.31 microdeletions. We report on a de novo intragenic deletion of the BMPR1A gene in a normally developing adolescent boy with short stature, delayed puberty, facial dysmorphism and an atrioventricular septal defect. Based on this finding, complemented with computational prioritization data and molecular evidence in literature, the critical region for CHD on 10q23 can be downsized to a single gene, BMPR1A. Although loss-of-function mutations in BMPR1A typically result in juvenile polyposis syndrome, none of the patients with the typical 10q22q23 microdeletion syndrome, comprising this gene, were reported to have juvenile polyposis thus far. We reason that, even in the absence of juvenile polyposis syndrome, sequencing and copy number analysis of BMPR1A should be considered in patients with (atrioventricular) septal defects, especially when associated with facial dysmorphism and anomalous growth. PMID- 22067611 TI - P16/p53 expression and telomerase activity in immortalized human dental pulp cells. AB - INTRODUCTION: Residing within human dental pulp are cells of an ectomesenchymal origin which have the potential to differentiate into odontoblast-like cells. These cells have a limited growth potential owing to the effects of cell senescence. This study examines the effects of immortalizing odontoblast-like cells on cell proliferation and mineralization by comparing transformed dental pulp stem cells (tDPSCs) and non-transformed dental pulp stem cells (nDPSCs). RESULTS: With the exogenous expression of hTERT, tDPSCs maintained a continued expression of odontogenic markers for cell proliferation and mineralization (ALP, COL-1, DMP-1, DSPP, OCN amd OPN)as did nDPScs. Oncoprotein expression was seen in both groups except for a noted absence of p16 in the tDPSCs. nDPSCs also showed lower levels of total ALP and DNA activity in comparison to tDPSCs when assayed as well as low telomerase activity readings. METHODS: Using a retroviral vector, exogenous human telomerase reverse transcriptase (hTERT) was expressed in tDPSCs. Both cell groups were cultured and their telomerase activities is determined using a telomerase quantification assay. Also examined were the expression of genes involved in proliferation and mineralization such as human alkaline phosphatase (ALP), beta-actin, collagen 1 (col-1), core binding factor (cbfa-1), dentin matrix protein (DMP-1), dentin sialophosphoprotein (DSPP), GAPDH, hTERT, osteocalcin (OCN), osteopontin (OPN) as well as oncoproteins involved in senescence (p16, p21 and p53) using RT-PCR. DNA and alkaline phosphatase activity was assayed in both cell groups. CONCLUSIONS: These results indicate maintainance of odontoblast-like differentiation characteristics after retroviral transformation with hTERT and suggest a possible link with a reduced p16 expression. PMID- 22067612 TI - Cholesterol-lowering efficacy of a microencapsulated bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 yoghurt formulation in hypercholesterolaemic adults. AB - Several studies have reported limited or no reduction in serum cholesterol in response to probiotic formulations. Recently, probiotics have shown promise in treating metabolic disease due to improved strain selection and delivery technologies. The aim of the present study was to evaluate the cholesterol lowering efficacy of a yoghurt formulation containing microencapsulated bile salt hydrolase (BSH)-active Lactobacillus reuteri NCIMB 30242, taken twice per d over 6 weeks, in hypercholesterolaemic adults. A total of 114 subjects completed this double-blind, placebo-controlled, randomised, parallel-arm, multi-centre study. This interventional study included a 2-week washout, 2-week run-in and 6-week treatment period. Subjects were randomised to consume either yoghurts containing microencapsulated L. reuteri NCIMB 30242 or placebo yoghurts. Over the intervention period, subjects consuming yoghurts containing microencapsulated L. reuteri NCIMB 30242 attained significant reductions in LDL-cholesterol (LDL-C) of 8.92 % (P = 0.016), total cholesterol (TC) of 4.81 % (P = 0.031) and non-HDL cholesterol (HDL-C) of 6.01 % (P = 0.029) over placebo, and a significant absolute change in apoB-100 of - 0.19 mmol/l (P = 0.049). Serum concentrations of TAG and HDL-C were unchanged over the course of the study. Present results show that consumption of microencapsulated BSH-active L. reuteri NCIMB 30242 yoghurt is efficacious and safe for lowering LDL-C, TC, apoB-100 and non-HDL-C in hypercholesterolaemic subjects. The efficacy of microencapsulated BSH-active L. reuteri NCIMB 30242 yoghurts appears to be superior to traditional probiotic therapy and akin to that of other cholesterol-lowering ingredients. PMID- 22067613 TI - Reconstituted HDL elicits marked changes in plasma lipids following single-dose injection in C57Bl/6 mice. AB - High-density lipoprotein (HDL)-targeting therapies, including reconstituted HDL (rHDL), are attractive agents for treating dyslipidemia and atherosclerosis, as they may increase HDL levels and enhance therapeutic activities associated with HDL, including reverse cholesterol transport (RCT). Using CSL-111, a rHDL consisting of native human apolipoprotein AI (hApoAI) and phospholipids, we characterized the acute effects of rHDL administration in C57Bl/6 mice to (i) further our understanding of the mechanism of action of rHDL, and (ii) evaluate the usefulness of the mouse as a preclinical model for HDL-targeting therapies. After a single injection of CSL-111, there was a dose- and time-dependent increase of hApoAI, human pre-beta HDL, total cholesterol, and triglycerides in serum, consistent with the effects of CSL-111 in humans. However, unlike in humans, there was no measurable increase in cholesteryl esters. Evaluated ex vivo, the ATP binding cassette A1 (ABCA1)- and scavenger receptor type BI (SR-BI) dependent cholesterol efflux capacity of serum from CSL-111-treated mice was increased compared with serum from vehicle-treated animals. Fractionation by size exclusion chromatography of lipoproteins in serum from treated mice revealed hApoAI in particles the size of endogenous HDL and slightly larger, cholesterol enriched particles of all sizes, including sizes distinct from endogenous HDL or CSL-111 itself, and triglyceride-enriched particles the size of very-low-density lipoprotein (VLDL). These results suggest that in mouse blood CSL-111 is remodeled and generates enhanced cholesterol efflux capacity which increases mobilization of free cholesterol from peripheral tissues. Our findings complement the previous reports on CSL-111 in human participants and provide data with which to evaluate the potential utility of mouse models in mechanistic studies of HDL targeting therapies. PMID- 22067614 TI - Acute electrical stimulation of the human retina with an epiretinal electrode array. AB - PURPOSE: To determine the threshold charges needed for eliciting visual perceptions through acute electrical stimulation of the human retina in patients suffering from retinitis pigmentosa, using an epiretinal microelectrode array. METHODS: In a multicentre study, 20 patients (average age 55 years) with visual acuities ranging from 4/200 to no light perception were included. The stimulation procedure was performed during a pars plana vitrectomy, for a maximum of 45 min, by using a microcontact film with IrO(x) electrodes connected by cable to a current generator. After repeated stimulation and threshold charge determination, the microelectrode array was removed. RESULTS: Nineteen of 20 patients stated in the postoperative interviews that they experienced one or more visual perceptions with close time correlation to single stimulation events. Minimum threshold charges needed to generate visual perceptions could be measured and verified in 15 patients. The charge level ranged from 20 to 768 nC with single or multiple electrodes. One patient suffered a retinal detachment during the procedure; this patient's retina was successfully reattached. There were no further adverse reactions observed during the 3-month follow-up. CONCLUSION: Acute epiretinal stimulation of the human retina, using a microelectrode array, can elicit visual perceptions in blind patients with retinitis pigmentosa. PMID- 22067615 TI - Transformation and regeneration of the holoparasitic plant Phelipanche aegyptiaca. AB - BACKGROUND: Transformation and subsequent regeneration of holoparasitic plants has never been reported, in part due to challenges in developing transformation protocols, but also because regeneration of obligate parasites is difficult since their survival depends completely on successful haustorium penetration of a host and the formation of vascular connections. The recent completion of a massive transcriptome sequencing project (the Parasitic Plant Genome Project) will fuel the use of genomic tools for studies on parasitic plants. A reliable system for holoparasite transformation is needed to realize the full value of this resource for reverse genetics and functional genomics studies. RESULTS: Here we demonstrate that transformation of Phelipanche aegyptiaca is achieved by infection of 3 month-old in vitro grown P. aegyptiaca calli with Agrobacterium rhizogenes harboring the yellow fluorescent protein (YFP). Four months later, YFP positive regenerated calli were inoculated onto tomato plants growing in a minirhizotron system. Eight days after inoculation, transgenic parasite tissue formed lateral haustoria that penetrated the host and could be visualized under UV illumination through intact host root tissue. YFP-positive shoot buds were observed one month after inoculation. CONCLUSIONS: This work constitutes a breakthrough in holoparasitic plant research methods. The method described here is a robust system for transformation and regeneration of a holoparasitic plant and will facilitate research on unique parasitic plant capabilities such as host plant recognition, haustorial formation, penetration and vascular connection. PMID- 22067616 TI - Effects of repeated stress on distal airway inflammation, remodeling and mechanics in an animal model of chronic airway inflammation. AB - BACKGROUND/AIMS: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. METHODS: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1-5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. RESULTS: The relative adrenal weight was greater in stressed guinea pigs compared to non stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. CONCLUSIONS: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling. PMID- 22067617 TI - Immunolocalization of Toll-like receptors 2 and 4 as well as their endogenous ligand, heat shock protein 70, in rat traumatic brain injury. AB - OBJECTIVE: Toll-like receptors (TLRs) are essential to the innate immune system for recognizing not only microbial pathogens but also endogenous ligands from injured cells, suggesting that TLRs are a sensitive detection system to tissue injury and play roles in initiating tissue degeneration/regeneration. In this study, the effects of traumatic brain injury (TBI) on lesional expression of TLR2, TLR4, their most common adaptor molecule myeloid differentiation factor 88 (MyD88) and their endogenous ligand, heat shock protein 70 (HSP70), were investigated. METHODS: Rat TBI was induced using an open-skull weight-drop model. TLR2, TLR4, MyD88 and HSP70 expression was studied by immunohistochemistry. RESULTS: TLR2, TLR4, HSP70 and MyD88 were mainly found in lesioned regions and subcortical white matter. While infiltration of TLR2+ cells became significant on day 2, significant accumulation of TLR4+, MyD88+ and HSP70+ cells was already seen on day 1, and the numbers of immunopositive cells increased continuously until day 4. Furthermore, double staining together with morphological classification showed that major cellular sources for TLR2, TLR4 and MyD88 were macrophages/microglia in lesioned areas and astrocytes in subcortical white matter. But for HSP70, the major cellular sources were neurons in perilesion and macrophages/microglia in lesion areas and astrocytes in subcortical white matter. DISCUSSION: In summary, our data reveal distinct patterns of localization of TLR+ resident and infiltrating cells in TBI rat brain. Infiltrating activated monocytic cells are the major source of TLR+ cells. These findings warrant further investigation of the roles of TLRs in controlling immune and degenerative/regenerative processes after TBI. PMID- 22067618 TI - Neuromyelitis optica immunoglobulin G in Chinese patients detected by immunofluorescence assay on a monkey brain substrate. AB - BACKGROUND: Serum neuromyelitis optica immunoglobulin G (NMO-IgG) is used as a biomarker to differentiate between neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the original assay is expensive and complex and shows low sensitivity. Here, we investigated the potential of NMO-IgG detection using an indirect immunofluorescence (IIF) assay on monkey brains. METHODS: NMO-IgG seroprevalence was determined in 168 samples by an IIF assay on a monkey brain substrate. The data were compared with those from a standard mouse brain IIF assay using McNemar and kappa tests. RESULTS: Thirty-one of 50 (62%) NMO patients, 7 of 18 (38.9%) longitudinally extensive transverse myelitis patients, 6 of 57 (10.5%) MS patients, and 5 of 10 (50%) optic neuritis patients were seropositive for NMO-IgG. None of the acute partial transverse myelitis patients (n = 3) or healthy controls (n = 20) was positive. Thus, the sensitivity of the test was 62% for the patients with clinically definite NMO. The specificity was 89.5%, considering the 57 MS patients as the control group. The modified IIF assay on monkey brains and the standard IIF assay based on mouse brains were not significantly different (McNemar test; p = 1.000). The two assays were concordant in 39 seropositive samples and 100 seronegative samples (kappa test; kappa = 0.592, p < 0.0001). CONCLUSIONS: Although the modified IIF monkey brain assay was no better than the standard mouse brain IIF assay, we affirmed that NMO-IgG is a sensitive and specific biomarker to differentiate between NMO and MS. PMID- 22067619 TI - Effect of gender and menstrual cycle on immune system response to acute mental stress: apoptosis as a mediator. AB - BACKGROUND/AIMS: We aimed to explore the immunological outcomes of short-term mental stress in apoptosis in peripheral lymphocytes and variations by gender and hormonal status of the individuals together with possible mediators of this interaction. METHODS: Acute mental stress (computerized Stroop color-word interference and cold pressor tests) was applied to men (n = 17) and women (n = 16, in both follicular and luteal phases). Heart rate and blood pressure were monitored throughout the test and after the test until baseline values were recorded. Blood samples were drawn for measuring cortisol and nitric oxide (NO) levels and flow-cytometric cell counting before and after the test. RESULTS: Activation of the stress system was ascertained by increased heart rate, blood pressure and serum cortisol levels after the test. Relative to baseline values, acute mental stress altered the distribution of T and natural killer cells. There was a significant decrease in T helper/T cytotoxic-suppressor cell ratio and an increase in apoptotic T helper cell percentage irrespective of gender or menstrual cycle phase. An increased number of natural killer cells was detected in women, whereas it was decreased in men. After stress induction, serum NO levels remained the same in women and increased in men. Although a correlation was not found between immune system changes and NO levels, glucocorticoids seem to have a role in the observed differences. CONCLUSION: Acute mental stress triggers apoptotic T helper cell loss which was associated with stress system activation, and sex steroids affect the pattern of stress-related immune cell distribution. PMID- 22067621 TI - Antioxidant status of bilirubin and uric acid in patients with myasthenia gravis. AB - Oxidative stress and changes in antioxidant status have been implicated in the pathogenesis of inflammatory and autoimmune diseases, and free radicals can cause considerable damage to the acetylcholine receptors. 388 individuals, including 97 patients with myasthenia gravis (MG), 135 patients with multiple sclerosis (MS) and 156 healthy controls, were assessed for serum levels of bilirubin and uric acid (UA), in order to determine the levels of these natural antioxidants in the serum. We found that serum UA levels in patients with MG were significantly lower (266.03 +/- 93.09 MUmol/l) compared with those of the healthy control group (338.87 +/- 107.10 MUmol/l, p = 0.001). However, there was no significant difference of serum UA levels between patients with MG and those with MS (p = 0.071). We also found that serum levels of total, direct and indirect bilirubin in patients with MG were significantly lower, compared with those in the healthy control group, whether male or female. From this study, we conclude that serum levels of bilirubin and UA are lower in MG patients. PMID- 22067620 TI - Neuroimmunoendocrine interactions in patients with recurrent major depression, increased early life stress and long-standing posttraumatic stress disorder symptoms. AB - BACKGROUND: Traumatic events experienced in childhood may lead to psychiatric diseases in adult life, including major depressive disorder (MDD). It remains obscure to what extent early life stress (ELS) is associated with biologically relevant changes in MDD. OBJECTIVE: We investigated both neuroendocrine and immunological correlates in recurrent MDD with ELS and current posttraumatic stress disorder symptoms. METHODS: Thirty-eight female MDD patients with or without childhood trauma and 15 healthy controls took part in this study. Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed by radioimmunoassays. Peripheral blood mononuclear cells (PBMCs) were isolated and T cell proliferation and cellular sensitivity to steroids and DHEAS were evaluated by colorimetric assays. Th1/Th2 cytokines were assessed by cytometric bead arrays. RESULTS: MDD patients with or without previous trauma had similarly lower salivary cortisol and DHEAS in parallel with blunted T cell proliferation. PBMCs of depressives were significantly less sensitive to dexamethasone or epinephrine than those of the controls. PBMCs of MDD patients produced significantly lower interleukin (IL)-2, IL-4 and tumor necrosis factor-alpha levels when compared to healthy controls. CONCLUSION: We found that a history of ELS did not modify the blunted neuroendocrine and immunological alterations presented by recurrent depressed patients. PMID- 22067622 TI - Melatonin membrane receptor type MT1 modulates cell-mediated immunity in the seasonally breeding tropical rodent Funambulus pennanti. AB - OBJECTIVE: Despite the evidence for melatonin membrane receptors (MT1R and MT2R) on lymphoid tissues in a wide range of seasonal breeders, their specific potency has never been compared and correlated with cell-mediated immunity. METHODS: We used luzindole, a nonselective MT2R antagonist, and 4-phenyl-2 propionamidotetralin (4P-PDOT), a selective MT2R antagonist, to assess the potency of the melatonin receptors MT1 and MT2 in melatonin-induced immunity under both in vivo as well as in vitro conditions. RESULTS: Physiological doses (25 MUg/100 g body weight in vivo and 100 and 500 pg/ml in vitro) of melatonin upregulated both MT1R and MT2R expression as well as splenocyte proliferation, while higher doses (100 and 500 MUg/100 g body weight in vivo and 1 ng/ml in vitro) downregulated splenocyte proliferation and the expression of both receptors. Luzindole antagonized the expression of both MT1R and MT2R in a dose dependent manner under in vivo as well as in vitro conditions, while 4P-PDOT blocked the expression of MT2R only during both experimental conditions. Splenocyte proliferation and IL-2 secretion (in vitro) followed the MT1R expression pattern, while the MT2R expression pattern showed no definite relation with either splenocyte proliferation or IL-2 secretion under in vivo and in vitro conditions. CONCLUSION: Immune function in tropical rodents is directly regulated by melatonin via its high-affinity membrane receptor MT1. MT1R plays a directive role in mediating splenocyte proliferation and IL-2 release, while the MT2R subtype appears not to be required for the immunoenhancing role of melatonin. PMID- 22067623 TI - Expression of Toll-like receptors 2, 4 and 9 in patients with Guillain-Barre syndrome. AB - OBJECTIVE: A myriad of transcription factors and inflammatory cytokines have been described to participate in the pathogenesis of Guillain-Barre syndrome (GBS). However, the innate immunity components--Toll-like receptors (TLRs)--have never been explored in this disease. We therefore investigated the expression of TLR2, 4 and 9 in the peripheral circulation of GBS patients as well as healthy controls. METHODS: Twenty-one GBS patients and 21 healthy donors participated in this study. Peripheral blood mononuclear cells were used for mRNA and protein analysis of TLR-related molecules. Also, peripheral blood mononuclear cells from different subjects were incubated with different TLR agonists and the subsequent IFN-gamma secretion was determined. RESULTS: Expression of TLR2, 4 and 9 as well as their related signaling molecules were higher in GBS patients compared to healthy controls. Disability scores of GBS patients had a strong positive correlation with the high levels of expression of TLR2, 4 and 9. CONCLUSIONS: The TLR signaling pathway may be involved in the pathogenesis of GBS. PMID- 22067625 TI - A mathematical model for simulating daily bed occupancy in an intensive care unit. AB - OBJECTIVES: To develop a mathematical model for simulating the daily bed occupancy in an intensive care unit. DESIGN: Data collection and retrospective analysis to develop a mathematical model for simulating daily bed occupancy in an intensive care unit. SETTING: We studied all admissions to the intensive care unit at the Hospital of Navarra over a 9-yr period. PATIENTS: Six-thousand three hundred adult patients consecutively admitted to intensive care units at a tertiary care hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The large set of data collected comprises an arrivals file, a patient file, and a bed occupancy file. The arrival file records the number of patients admitted to the intensive care unit each day, by admission type, and by day of the week. The patient file contains records for all patients admitted to the intensive care unit during the study period: Admission type, admission and discharge dates, age, sex, Acute Physiology and Chronic Health Evaluation II score within the first 24 hrs, infections during hospitalization, and mortality. We used these two files to fit appropriate statistical models of arrival rates and length of stay by patient type. Based on this statistical analysis and the representation of the intensive care unit as a queuing problem, we built a simulation model. The bed occupancy file records the number of occupied beds at 4:00 PM each day. We used this file to validate the simulation model by testing the similarity of the real and simulated output data. The simulation model also includes bed management decisions related to patient discharge. RESULTS: We obtained a valid simulation model that reproduced on a computer the patient flow through the intensive care unit at the Hospital of Navarra. This computerized simulation model can be used to study the intensive care unit bed occupancy profile and can be used as a reliable sizing and capacity analysis tool. As an example, we present the problem of estimating the number of beds needed to meet an increase in patient arrivals at the intensive care unit because of different causes. CONCLUSIONS: It is possible to develop simulation models that can be used to predict future intensive care unit resource needs. PMID- 22067624 TI - Mild hypothermia decreases fentanyl and midazolam steady-state clearance in a rat model of cardiac arrest. AB - OBJECTIVES: Therapeutic hypothermia is widely employed for neuroprotection after cardiac arrest. However, concern regarding elevated drug concentrations during hypothermia and increased adverse drug reaction risk complicates concurrent pharmacotherapy. Many commonly used medications in critically ill patients rely on the cytochrome P450 3A isoform for their elimination. Therefore, our study objectives were to determine the effect of mild hypothermia on the in vivo pharmacokinetics of fentanyl and midazolam, two clinically relevant cytochrome P450 3A substrates, after cardiac arrest and to investigate the mechanisms of these alterations. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Thirty-two adult male Sprague-Dawley rats. INTERVENTIONS: An asphyxial cardiac arrest rat model was used and mild hypothermia (33 degrees C) was induced 1 hr post injury by surface cooling and continued for 10 hrs to mimic the prolonged clinical application of hypothermia accompanied by intensive care interventions. Fentanyl and midazolam were independently administered by intravenous infusion and plasma and brain concentrations were analyzed using ultraperformance liquid chromatography tandem mass spectrometry. Cytochrome P450 3a2 protein expression was measured and a Michaelis-Menten enzyme kinetic analysis was performed at 37 degrees C and 33 degrees C using control rat microsomes. MEASUREMENTS AND MAIN RESULTS: Mild hypothermia decreased the systemic clearance of both fentanyl (61.5 +/- 11.5 to 48.9 +/- 8.95 mL/min/kg; p < .05) and midazolam (89.2 +/- 12.5 to 73.6 +/- 12.1 mL/min/kg; p < .05) after cardiac arrest. The elevated systemic concentrations did not lead to parallel increased brain exposures of either drug. Mechanistically, no differences in cytochrome P450 3a2 expression was observed, but the in vitro metabolism of both drugs was decreased at 33 degrees C vs. 37 degrees C through reductions in enzyme metabolic capacity rather than substrate affinity. CONCLUSIONS: Mild hypothermia reduces the systemic clearances of fentanyl and midazolam in rats after cardiac arrest through alterations in cytochrome P450 3a2 metabolic capacity rather than enzyme affinity as observed with other cytochrome P450s. Contrasting effects on blood and brain levels further complicates drug dosing. Consideration of the impact of hypothermia on medications whose clearance is dependent on P450 3A metabolism is warranted. PMID- 22067626 TI - Herpes simplex virus encephalitis despite normal cell count in the cerebrospinal fluid. AB - OBJECTIVES: To describe herpes simplex virus encephalitis despite normal cell count in the cerebrospinal fluid in patients with malignoma after whole brain irradiation. INTERVENTIONS: Blood and cerebrospinal fluid analysis and magnetic resonance imaging. MEASUREMENTS AND MAIN RESULTS: Three male and two female patients with malignoma and a recent history of whole-brain irradiation presented with impaired consciousness with or without epileptic seizure. Although cerebrospinal fluid analysis revealed a normal cell count, herpes simplex virus DNA was detected in all samples by polymerase chain reaction. CONCLUSIONS: In patients with impaired consciousness, epileptic seizure, or temporal lobe symptoms of new onset and a recent history of brain irradiation with normal cerebrospinal fluid, an atypical anergic course of herpes simplex virus encephalitis should be considered. Herpes simplex virus polymerase chain reaction should be used as method of choice to detect herpes simplex virus genomes as early as possible rather than relying on routine cerebrospinal fluid parameters. Importantly, antiviral therapy should be started without delay in any case of faint suspicion and should be continued until herpes simplex virus encephalitis is clearly ruled out. PMID- 22067628 TI - Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*. AB - OBJECTIVES: To evaluate the efficacy and safety of short-term low-dose intravenous haloperidol for delirium prevention in critically ill elderly patients after noncardiac surgery. DESIGN: Prospective, randomized, double-blind, and placebo-controlled trial in two centers. SETTING: Intensive care units of two large tertiary teaching hospitals. PATIENTS: Four hundred fifty-seven patients 65 yrs or older who were admitted to the intensive care unit after noncardiac surgery. INTERVENTION: Haloperidol (0.5 mg intravenous bolus injection followed by continuous infusion at a rate of 0.1 mg/h for 12 hrs; n = 229) or placebo (n = 228) was randomly administered from intensive care unit admission. MEASURES: The primary end point was the incidence of delirium within the first 7 days after surgery. Secondary end points included time to onset of delirium, number of delirium-free days, length of intensive care unit stay, all-cause 28-day mortality, and adverse events. Delirium was assessed using the confusion assessment method for the intensive care unit. RESULTS: The incidence of delirium during the first 7 days after surgery was 15.3% (35/229) in the haloperidol group and 23.2% (53/228) in the control group (p = .031). The mean time to onset of delirium and the mean number of delirium-free days were significantly longer (6.2 days [95% confidence interval 5.9-6.4] vs. 5.7 days [95% confidence interval 5.4 6.0]; p = .021; and 6.8 +/- 0.5 days vs. 6.7 +/- 0.8 days; p = .027, respectively), whereas the median length of intensive care unit stay was significantly shorter (21.3 hrs [95% confidence interval 20.3-22.2] vs. 23.0 hrs [95% confidence interval 20.9-25.1]; p = .024) in the haloperidol group than in the control group. There was no significant difference with regard to all-cause 28-day mortality between the two groups (0.9% [2/229] vs. 2.6% [6/228]; p = .175). No drug-related side effects were documented. CONCLUSIONS: For elderly patients admitted to intensive care unit after noncardiac surgery, short-term prophylactic administration of low-dose intravenous haloperidol significantly decreased the incidence of postoperative delirium. The therapy was well tolerated. PMID- 22067627 TI - The acute pulmonary inflammatory response to the graded severity of smoke inhalation injury. AB - OBJECTIVES: To determine whether the graded severity of smoke inhalation is reflected by the acute pulmonary inflammatory response to injury. DESIGN: In a prospective observational study, we assessed the bronchoalveolar lavage fluid for both leukocyte differential and concentration of 28 cytokines, chemokines, and growth factors. Results were then compared to the graded severity of inhalation injury as determined by Abbreviated Injury Score criteria (0, none; 1, mild; 2, moderate; 3, severe; 4, massive). SETTING: All patients were enrolled at a single tertiary burn center. PATIENTS: The bronchoalveolar lavage fluid was obtained from 60 patients within 14 hrs of burn injury who underwent bronchoscopy for suspected smoke inhalation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Those who presented with worse grades of inhalation injury had higher plasma levels of carboxyhemoglobin and enhanced airway neutrophilia. Patients with the most severe inhalation injuries also had a greater requirement for tracheostomy, longer time on the ventilator, and a prolonged stay in the intensive care unit. Of the 28 inflammatory mediators assessed in the bronchoalveolar lavage fluid, 21 were at their highest in those with the worst inhalation injury scores (grades 3 and 4), the greatest of which was interleukin-8 (92,940 pg/mL, grade 4). When compared in terms of low inhalation injury (grades 1-2) vs. high inhalation injury (grades 3-4), we found significant differences between groups for interleukin-4, interleukin-6, interleukin-9, interleukin-15, interferon-gamma, granulocyte-macrophage colony-stimulating factor, and monocyte chemotactic protein-1 (p < .05 for all). CONCLUSIONS: These data reveal that the degree of inhalation injury has basic and profound effects on burn patient morbidity, evokes complex changes of multiple alveolar inflammatory proteins, and is a determinant of the pulmonary inflammatory response to smoke inhalation. Accordingly, future investigations should consider inhalation injury to be a graded phenomenon. PMID- 22067629 TI - The surgical intensive care unit optimal mobility score predicts mortality and length of stay. AB - OBJECTIVES: To test if the surgical intensive care unit optimal mobility score predicts mortality and intensive care unit and hospital length of stay. DESIGN: Prospective single-center cohort study. SETTING: Surgical intensive care unit of the Massachusetts General Hospital. PATIENTS: One hundred thirteen consecutive patients admitted to the surgical intensive care unit. INVESTIGATIONS: We tested the hypotheses that the surgical intensive care unit optimal mobility score independent of comorbidity index, Acute Physiology and Chronic Health Evaluation II, creatinine, hypotension, hypernatremia, acidosis, hypoxia, and hypercarbia predicts hospital mortality, surgical intensive care unit and total hospital length of stay. MEASUREMENTS AND MAIN RESULTS: Two nurses independently predicted the patients' mobilization capacity by using the surgical intensive care unit optimal mobility score the morning after admission, whereas a third nurse recorded the achieved mobilization levels of patients at the end of the day. A multidisciplinary expert team measured patients' grip strength and assessed their predicted mobilization capacity independently. Multivariate analysis revealed that the surgical intensive care unit optimal mobility score was the only independent predictor of mortality. Surgical intensive care unit optimal mobility score, hypotension, and hypernatremia (>144 mmol/L) independently predicted intensive care unit length of stay, whereas the surgical intensive care unit optimal mobility score and hypernatremia predicted total hospital length of stay. The Acute Physiology and Chronic Health Evaluation II score was not identified in the multivariate analysis. The surgical intensive care unit optimal mobility score was also a reliable and valid instrument in predicting achieved mobilization levels of patients. CONCLUSIONS: In surgical critically ill patients presenting without preexisting impairment of functional mobility, the surgical intensive care unit optimal mobility score is a reliable and valid tool to predict mortality and intensive care unit and hospital length of stay. PMID- 22067630 TI - Oxygen blood transport during experimental sepsis: effect of hypothermia*. AB - OBJECTIVES: The aim of this study was to highlight the link between induced hypothermia and increased survival duration as observed in the septic model developed by the laboratory. To reach this objective, survival duration and blood oxygen transport capacity were measured at two temperatures-38 degrees C (induced normothermia) and 34 degrees C (induced hypothermia)-in septic rats. DESIGN: A prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: Forty-four male Sprague-Dawley rats (median weight, 232 g; range, 200-303 g). INTERVENTIONS: After anesthesia and obtention of the temperature goal, sepsis was induced by cecal ligation and perforation. MEASUREMENTS AND MAIN RESULTS: Sepsis induction led to death 5 hrs 11 mins +/- 0 hr 36 mins after cecal ligation and perforation at 38 degrees C. At this temperature, significant changes in blood oxygen transport capacity were observed in septic rats; Hill number decreased from 2.36 +/- 0.10 (baseline group) to 1.99 +/- 0.17 (septic group) (p = .008) and oxygen-hemoglobin affinity decreased and P50 increased from 41.40 +/- 2.4 Torr (baseline group) to 51.17 +/- 14.07 Torr (septic group). Furthermore, in normothermia, a significant increase of creatinine and albumin plasmatic concentrations was observed 4 hrs after sepsis induction. Survival duration was significantly higher in induced hypothermia (7 hrs 22 mins +/- 0 hr 12 mins at 34 degrees C) compared with induced normothermia. At 34 degrees C, no significant change in blood oxygen transport capacity was observed. In the same way, exposure to 34 degrees C induced no change in measured plasmatic parameters except an increase in albumin concentration in septic rats compared with the baseline group. CONCLUSIONS: Sepsis led to a decrease of both oxygen hemoglobin cooperativity and affinity at 38 degrees C. By contrast, no change in these parameters was observed when sepsis was induced during hypothermia. Taken together, these results could be interpreted in normothermia septic rats as an adaptive mechanism that could enhance the release of oxygen at the tissue level. Hypothermia by slowing down sepsis evolution could increase survival duration. PMID- 22067631 TI - Impact of real-time electronic alerting of acute kidney injury on therapeutic intervention and progression of RIFLE class. AB - OBJECTIVE: To evaluate whether a real-time electronic alert system or "AKI sniffer," which is based on the RIFLE classification criteria (Risk, Injury and Failure), would have an impact on therapeutic interventions and acute kidney injury progression. DESIGN: Prospective intervention study. SETTING: Surgical and medical intensive care unit in a tertiary care hospital. PATIENTS: A total of 951 patients having in total 1,079 admission episodes were admitted during the study period (prealert control group: 227, alert group: 616, and postalert control group: 236). INTERVENTIONS: Three study phases were compared: A 1.5-month prealert control phase in which physicians were blinded for the acute kidney injury sniffer and a 3-month intervention phase with real-time alerting of worsening RIFLE class through the Digital Enhanced Cordless Technology telephone system followed by a second 1.5-month postalert control phase. MEASUREMENTS AND MAIN RESULTS: A total of 2593 acute kidney injury alerts were recorded with a balanced distribution over all study phases. Most acute kidney injury alerts were RIFLE class risk (59.8%) followed by RIFLE class injury (34.1%) and failure (6.1%). A higher percentage of patients in the alert group received therapeutic intervention within 60 mins after the acute kidney injury alert (28.7% in alert group vs. 7.9% and 10.4% in the pre- and postalert control groups, respectively, p MU .001). In the alert group, more patients received fluid therapy (23.0% vs. 4.9% and 9.2%, p MU .01), diuretics (4.2% vs. 2.6% and 0.8%, p MU .001), or vasopressors (3.9% vs. 1.1% and 0.8%, p MU .001). Furthermore, these patients had a shorter time to intervention (p MU .001). A higher proportion of patients in the alert group showed return to a baseline kidney function within 8 hrs after an acute kidney injury alert "from normal to risk" compared with patients in the control group (p = .048). CONCLUSIONS: The real-time alerting of every worsening RIFLE class by the acute kidney injury sniffer increased the number and timeliness of early therapeutic interventions. The borderline significant improvement of short-term renal outcome in the RIFLE class risk patients needs to be confirmed in a large multicenter trial. PMID- 22067632 TI - Automated grain mapping using wide angle convergent beam electron diffraction in transmission electron microscope for nanomaterials. AB - The grain size statistics, commonly derived from the grain map of a material sample, are important microstructure characteristics that greatly influence its properties. The grain map for nanomaterials is usually obtained manually by visual inspection of the transmission electron microscope (TEM) micrographs because automated methods do not perform satisfactorily. While the visual inspection method provides reliable results, it is a labor intensive process and is often prone to human errors. In this article, an automated grain mapping method is developed using TEM diffraction patterns. The presented method uses wide angle convergent beam diffraction in the TEM. The automated technique was applied on a platinum thin film sample to obtain the grain map and subsequently derive grain size statistics from it. The grain size statistics obtained with the automated method were found in good agreement with the visual inspection method. PMID- 22067633 TI - [Access of French-speaking elderly to nursing homes among minorities, a linguistic challenge for health and greater welfare]. AB - Access to long-term nursing homes by French-speaking seniors in minority situations is a very real problem. However, few studies have been conducted on this subject. We wanted to better understand this issue in New Brunswick while taking into account the language aspect. In this article, we will present the problem based on different issues encountered by Francophones in minority situations and by giving an overview of the studies conducted on French-speaking seniors in minority situations. We will then address the issue related to the rights of French-speaking senior to receive services in French in nursing homes by analyzing briefly the province's legal requirements. Furthermore, we will present the regulatory framework of nursing homes in New Brunswick. Finally, we will provide a geographic analysis of existing New Brunswick nursing homes while taking into account the language aspect, the levels of service and the distribution of French-speaking seniors within the territory. PMID- 22067634 TI - Predictors of multiple sclerosis in children and implications for early initiation of treatment. PMID- 22067635 TI - MRI parameters for prediction of multiple sclerosis diagnosis in children with acute CNS demyelination: a prospective national cohort study. AB - BACKGROUND: Multiple sclerosis (MS) diagnostic criteria incorporate MRI features that can be used to predict later diagnosis of MS in adults with acute CNS demyelination. To identify MRI predictors of a subsequent MS diagnosis in a paediatric population, we created a standardised scoring method and applied it to MRI scans from a national prospective incidence cohort of children with CNS demyelination. METHODS: Clinical and MRI examinations were done at the onset of acute CNS demyelination and every 3 months in the first year after that, and at the time of a second demyelinating attack. MS was diagnosed on the basis of clinical or MRI evidence of relapsing disease. Baseline MRI scans were assessed for the presence of 14 binary response parameters. Parameters were assessed with a multiple tetrachoric correlation matrix. Univariate analyses and multivariable Cox proportional hazards models were used to identify predictors of MS. FINDINGS: Between Sept 1, 2004, and June 30, 2010, 332 children and adolescents were assessed for eligibility. 1139 scans were available from 284 eligible participants who had been followed up for 3.9 (SD 1.7) years. 57 (20%) were diagnosed with MS after a median of 188 (IQR 144-337) days. Seven of 14 binary response parameters were retained. The presence of either one or more T1-weighted hypointense lesions (hazard ratio 20.6, 95% CI 5.46-78.0) or one or more periventricular lesions (3.34, 1.27-8.83) was associated with an increased likelihood of MS diagnosis (sensitivity 84%, specificity 93%, positive predictive value 76%, negative predictive value 96%). Risk for MS diagnosis was highest when both parameters were present (34.27, 16.69-70.38). Although the presence of contrast enhancement, cerebral white matter, intracallosal, and brainstem lesions was associated with MS in the univariate analyses, these parameters were not retained in the multivariable models. INTERPRETATION: Specific MRI parameters can be used to predict diagnosis of MS in children with incident demyelination of the CNS. The ability to promptly identify children with MS will enhance timely access to care and will be important for future clinical trials in paediatric MS. FUNDING: Canadian Multiple Sclerosis Scientific Research Foundation. PMID- 22067636 TI - Chemotherapeutic errors in hospitalised cancer patients: attributable damage and extra costs. AB - BACKGROUND: In spite of increasing efforts to enhance patient safety, medication errors in hospitalised patients are still relatively common, but with potentially severe consequences. This study aimed to assess antineoplastic medication errors in both affected patients and intercepted cases in terms of frequency, severity for patients, and costs. METHODS: A 1-year prospective study was conducted in order to identify the medication errors that occurred during chemotherapy treatment of cancer patients at a French university hospital. The severity and potential consequences of intercepted errors were independently assessed by two physicians. A cost analysis was performed using a simulation of potential hospital stays, with estimations based on the costs of diagnosis-related groups. RESULTS: Among the 6, 607 antineoplastic prescriptions, 341 (5.2%) contained at least one error, corresponding to a total of 449 medication errors. However, most errors (n = 436) were intercepted before medication was administered to the patients. Prescription errors represented 91% of errors, followed by pharmaceutical (8%) and administration errors (1%). According to an independent estimation, 13.4% of avoided errors would have resulted in temporary injury and 2.6% in permanent damage, while 2.6% would have compromised the vital prognosis of the patient, with four to eight deaths thus being avoided. Overall, 13 medication errors reached the patient without causing damage, although two patients required enhanced monitoring. If the intercepted errors had not been discovered, they would have resulted in 216 additional days of hospitalisation and cost an estimated annual total of 92,907?, comprising 69,248? (74%) in hospital stays and 23,658? (26%) in additional drugs. CONCLUSION: Our findings point to the very small number of chemotherapy errors that actually reach patients, although problems in the chemotherapy ordering process are frequent, with the potential for being dangerous and costly. PMID- 22067638 TI - The benefits of intermittent self-catheterization. PMID- 22067639 TI - Improving staff engagement and patient care: use of novel initiatives. AB - Staff engagement and patient care are two key aspects of the healthcare system. Sandwell and West Birmingham Hospitals (SWBH) NHS Trust is focused on achieving excellence in these areas and has used innovative initiatives to realize these aims. Listening into Action (LiA) is a comprehensive outcome-orientated approach which is aimed at harnessing the ideas of frontline staff. LiA has led to improvement in results from staff surveys and the fostering of a more collaborative approach. The Trust has started to use a Foley catheter tray with the aim of improving catheter procedures. The Foley catheter trays, which include all the necessary equipment for an aseptic catheterization, were introduced across the Trust over a 4-week period. Uptake and implementation were excellent with the use of the Foley catheter tray, and were associated with a reduction in catheterization time. PMID- 22067640 TI - Using behavioural methods to manage faecal incontinence. AB - Faecal incontinence is a common problem for patients who have suffered a stroke. However, patients arriving at a neurorehabilitation unit are often reluctant to disclose their problem, and transfer documentation is sometimes incomplete. Nurses need to be aware that this is a sensitive area for patients, which can adversely affect their rehabilitation progress. Nurses and other professional practitioners must work together as a team, as the impact of faecal incontinence can be highly distressing for patients, and can result in inefficient use of therapy time. This article examines how the rehabilitation nurse, using evidence based practice, can manage faecal incontinence effectively within a structured assessment and therapy programme, and shows it is possible to manage patients' bowel actions proactively. The benefits of this include maximizing therapy and nursing time and preventing delayed discharges. This article is based on a thorough assessment originating from a case study. PMID- 22067641 TI - Management of psoriasis and its comorbidities in primary care. AB - Psoriasis is a common chronic disfiguring skin disease. Its management depends on the extent of disease, sites affected, comorbidities, and patient's background or lifestyle. In the UK, psoriasis treatment starts in the primary care with range of topical applications, including steroids, vitamin D analogues and coal tar. However, psoriasis is associated with physical, psychological and metabolic comorbidities which could not be improved by topical therapy. The aim of this review is to address the challenge in managing these comorbidities within primary care. PMID- 22067642 TI - Nurse-led homeless intermediate care: an economic evaluation. AB - This article describes a homeless intermediate care pilot project that took place at a 120-bedded homeless hostel in South London in 2009. During the year, 34 hostel clients directly benefited from intermediate care. At the end of the year, the number of hospital admissions to the hostel had dropped 77% relative to 2008, and the number of accident and emergency (A&E) attendances had dropped 52%. Hospital 'did not attends' (DNAs) were 22% lower. An economic evaluation found that the pilot project was cost neutral overall, and there is some evidence that health outcomes improved. The project now has mainstream funding and has recently received a national community nursing award. Its success has been recognized nationally as an example of innovative practice in work with vulnerable groups (Department of Health (DH), 2010). PMID- 22067643 TI - To pray or not to pray: a question of ethics. AB - There is a widespread belief that nurses have a duty to provide spiritual care. However, many feel there is still a need for debate surrounding the ethical use of prayer in both nursing research and practice. By using critical reflections and evidence-based literature, this paper develops a discourse on the ethics of prayer as a spiritual intervention in nursing and health care practice. Several key ethical issues are highlighted. In regards to research, lack of informed consent is a major concern in both research and nursing practice. Key ethical issues in practice include questions around intention and authority, e.g. despite the religious beliefs of the nurse, intentions to proselytize must be avoided to protect patient autonomy and avoid abuse of the nurse's authority. Furthermore, prayer has unknown side effects and implications. This paper concludes that, in practice, nurses must reconcile their personal, spiritual beliefs with their professional duties, and while this may be a delicate balance, it is not yet appropriate to encourage or dissuade a patient from their beliefs until appropriate research evidence is produced. PMID- 22067644 TI - Supporting the self and others: from staff nurse to nurse consultant. Part 10: confidentiality. PMID- 22067645 TI - Can older nurses still provide care? PMID- 22067646 TI - Tooling up for patient safety: 'seeing is believing'. PMID- 22067647 TI - Smoking cessation: implementing hospital-based services. AB - Smoking cessation services are well established in the community. In recent years, an increase in their availability has been recommended and secondary care settings were identified as suitable locations. This article draws on the evidence base underpinning this move and uses findings from an evaluation of such a service introduced into an acute hospital to illustrate the key principles to be considered. These principles included receptiveness of the hospital environment to the smoking cessation message, the importance of organizational preparation before launching the service, collaboration within the hospital and in the community, resourcing of the initiative, training of staff and providing feedback to staff on progress (e.g. quit rates resulting from initiative). The paper concludes that broad acceptance at all levels within the hospital, which enhances a stop smoking culture, in parallel with an in-depth preparation and training period, is required to successfully launch a hospital-based stop smoking service. PMID- 22067648 TI - The essence of the role of the nurse as teacher. PMID- 22067649 TI - Education that works in practice. PMID- 22067650 TI - Actomyosin contractililty: force power drives tumor growth. PMID- 22067651 TI - Ribosome biogenesis and p53: who is regulating whom? PMID- 22067652 TI - (H)if blood stem cells gO2 sleep: what can wake them up? PMID- 22067653 TI - Lineage reprogramming: a shortcut to generating functional neurons from fibroblasts. PMID- 22067654 TI - A novel role for activation-induced cytidine deaminase: central B-cell tolerance. PMID- 22067655 TI - Insulin resistance due to nutrient excess: is it a consequence of AMPK downregulation? AB - It has long been known that excesses of glucose and branched chain amino acids, such as leucine, lead to insulin resistance in skeletal muscle. A recent study in incubated rat muscle suggests that both molecules may do so by virtue of their ability to downregulate the fuel sensing and signaling enzyme AMP-activated protein kinase (AMPK) and activate mTOR/p70S6 kinase (p70S6K) signaling. The results also demonstrated that inhibition of mTOR/p70S6K with rapamycin prevented the development of insulin resistance but had no effect on AMPK activity (Thr172 phosphorylation of its catalytic subunit). In contrast, activation of AMPK by both AICAR and alpha-lipoic acid led to the phosphorylation of specific molecules that diminished both mTOR/p70S6K signaling and insulin resistance. These findings suggest that downregulation of AMPK precedes mTOR/p70S6K activation in mediating glucose and leucine-induced insulin resistance, although the mechanism by which it does so remains to be determined. Also requiring study is how an excess of the two nutrients leads to AMPK downregulation. PMID- 22067656 TI - Bioenergy sensing in the brain: the role of AMP-activated protein kinase in neuronal metabolism, development and neurological diseases. AB - Bioenergy homeostasis constitutes one of the most crucial foundations upon which other cellular and organismal processes may be executed. AMP-activated protein kinase (AMPK) has been shown to be the key player in the regulation of energy metabolism, and thus is becoming the focus of research on obesity, diabetes and other metabolic disorders. However, its role in the brain, the most energy consuming organ in our body, has only recently been studied and appreciated. Widely expressed in the brain, AMPK activity is tightly coupled to the energy status at both neuronal and whole-body levels. Importantly, AMPK signaling is intimately implicated in multiple aspects of brain development and function including neuronal proliferation, migration, morphogenesis and synaptic communication, as well as in pathological conditions such as neuronal cell death, energy depletion and neurodegenerative disorders. PMID- 22067657 TI - Effects of conditional depletion of topoisomerase II on cell cycle progression in mammalian cells. AB - Topoisomerase II (Topo II) that decatenates newly synthesized DNA is targeted by many anticancer drugs. Some of these drugs stabilize intermediate complexes of DNA with Topo II and others act as catalytic inhibitors of Topo II. Simultaneous depletion of Topo IIalpha and Topo IIbeta, the two isoforms of mammalian Topo II, prevents cell growth and normal mitosis, but the role of Topo II in other phases of mammalian cell cycle has not yet been elucidated. We have developed a derivative of p53-suppressed human cells with constitutive depletion of Topo IIbeta and doxycycline-regulated conditional depletion of Topo IIalpha. The effects of Topo II depletion on cell cycle progression were analyzed by time lapse video microscopy, pulse-chase flow cytometry and mitotic morphology. Topo II depletion increased the duration of the cell cycle and mitosis, interfered with chromosome condensation and sister chromatid segregation and led to frequent failure of cell division, ending in either cell death or restitution of polyploid cells. Topo II depletion did not change the rate of DNA replication but increased the duration of G 2. These results define the effects of decreased Topo II activity, rather than intermediate complex stabilization, on the mammalian cell cycle. PMID- 22067659 TI - Single molecule experimentation in biological physics: exploring the living component of soft condensed matter one molecule at a time. AB - The soft matter of biological systems consists of mesoscopic length scale building blocks, composed of a variety of different types of biological molecules. Most single biological molecules are so small that 1 billion would fit on the full-stop at the end of this sentence, but collectively they carry out the vital activities in living cells whose length scale is at least three orders of magnitude greater. Typically, the number of molecules involved in any given cellular process at any one time is relatively small, and so real physiological events may often be dominated by stochastics and fluctuation behaviour at levels comparable to thermal noise, and are generally heterogeneous in nature. This challenging combination of heterogeneity and stochasticity is best investigated experimentally at the level of single molecules, as opposed to more conventional bulk ensemble-average techniques. In recent years, the use of such molecular experimental approaches has become significantly more widespread in research laboratories around the world. In this review we discuss recent experimental approaches in biological physics which can be applied to investigate the living component of soft condensed matter to a precision of a single molecule. PMID- 22067660 TI - Focus on central venous pressure monitoring in an acute care setting. PMID- 22067658 TI - Networks of intergenic long-range enhancers and snpRNAs drive castration resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders. AB - The mechanistic relevance of intergenic disease-associated genetic loci (IDAGL) containing highly statistically significant disease-linked SNPs remains unknown. Here, we present experimental and clinical evidence supporting the importantance of the role of IDAGL in human diseases. A targeted RT-PCR screen coupled with sequencing of purified PCR products detects widespread transcription at multiple IDAGL and identifies 96 small noncoding trans-regulatory RNAs of ~100-300 nt in length containing SNPs (snpRNAs) associated with 21 common disorders. Multiple independent lines of experimental evidence support functionality of snpRNAs by documenting their cell type-specific expression and evolutionary conservation of sequences, genomic coordinates and biological effects. Chromatin state signatures, expression profiling experiments and luciferase reporter assays demonstrate that many IDAGL are Polycomb-regulated long-range enhancers. Expression of snpRNAs in human and mouse cells markedly affects cellular behavior and induces allele-specific clinically relevant phenotypic changes: NLRP1-locus snpRNAs rs2670660 exert regulatory effects on monocyte/macrophage transdifferentiation, induce prostate cancer (PC) susceptibility snpRNAs and transform low-malignancy hormone-dependent human PC cells into highly malignant androgen-independent PC. Q-PCR analysis and luciferase reporter assays demonstrate that snpRNA sequences represent allele-specific "decoy" targets of microRNAs that function as SNP allele-specific modifiers of microRNA expression and activity. We demonstrate that trans-acting RNA molecules facilitating resistance to androgen depletion (RAD) in vitro and castration-resistant phenotype (CRP) in vivo of PC contain intergenic 8q24-locus SNP variants (rs1447295; rs16901979; rs6983267) that were recently linked with increased risk of PC. Q-PCR analysis of clinical samples reveals markedly increased and highly concordant (r = 0.896; p < 0.0001) snpRNA expression levels in tumor tissues compared with the adjacent normal prostate [122-fold and 45-fold in Gleason 7 tumors (p = 0.03); 370-fold and 127-fold in Gleason 8 tumors (p = 0.0001) for NLRP1-locus and 8q24-locus snpRNAs, respectively]. Our experiments indicate that RAD and CR phenotype of human PC cells can be triggered by ncRNA molecules transcribed from the NLRP1-locus intergenic enhancer at 17p13 and by downstream activation of the 8q24-locus snpRNAs. Our results define the IDAGL at 17p13 and 8q24 as candidate regulatory loci of RAD and CR phenotypes of PC, reveal previously unknown molecular links between the innate immunity/inflammasome system and development of hormone-independent PC and identify novel molecular and genetic targets with diagnostic and therapeutic potentials, exploration of which should be highly beneficial for personalized clinical management of PC. PMID- 22067662 TI - Return on public health investment: CDC's Expanded HIV Testing Initiative. AB - BACKGROUND: Over a 3-year period, the Centers for Disease Control and Prevention invested $102.3 million in a large-scale HIV testing program, the Expanded HIV Testing Initiative for populations disproportionally affected by HIV. Policy makers, who must optimize public health given a set budget, are interested in the financial return on investment (ROI) of large-scale HIV testing. METHODS: We conducted an ROI analysis using expenditure and outcome data from the program. A health system perspective was used that included all program expenditures including medical costs of treating newly diagnosed patients. We incorporated benefits of HIV transmissions averted from persons diagnosed of their infection through the Initiative compared with when, on average, those persons would have been diagnosed without the Initiative (3 years later in the base case). HIV transmissions were derived from a published mathematical model of HIV transmission. In sensitivity analysis, we tested the effect of 1-year to 5-year alternate testing intervals and differences in the prevalence of undiagnosed HIV infection. RESULTS: Under the Initiative, 2.7 million persons were tested for HIV, there was a newly diagnosed HIV positivity rate of 0.7%, and an estimated 3381 HIV infections were averted. It achieved a return of $1.95 for every dollar invested. ROI ranged from $1.46 to $2.01 for alternative testing intervals of 1-5 years and remained above $1 (positive return on investment) with a prevalence of undiagnosed HIV infection as low as 0.12%. CONCLUSIONS: The expanded testing Initiative yielded ROI values of >$1 under a broad range of sensitivity analyses and provides further support for large-scale HIV testing programs. PMID- 22067661 TI - A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. AB - INTRODUCTION: Effective treatment of HIV-associated distal sensory polyneuropathy remains a significant unmet therapeutic need. METHODS: In this randomized, double blind, controlled study, patients with pain due to HIV-associated distal sensory polyneuropathy received a single 30-minute or 60-minute application of NGX-4010- a capsaicin 8% patch (n = 332)--or a low-dose capsaicin (0.04%) control patch (n = 162). The primary endpoint was the mean percent change from baseline in Numeric Pain Rating Scale score to weeks 2-12. Secondary endpoints included patient global impression of change at week 12. RESULTS: Pain reduction was not significantly different between the total NGX-4010 group (-29.5%) and the total control group (-24.5%; P = 0.097). Greater pain reduction in the 60-minute ( 30.0%) versus the 30-minute control group (-19.1%) prevented intended pooling of the control groups to test individual NGX-4010 treatment groups. No significant pain reduction was observed for the 30-minute NGX-4010 group compared with 30 minute control (-26.2% vs.-19.1%, respectively, P = 0.103). Pain reductions in the 60-minute NGX-4010 and control groups were comparable (-32.8% vs. -30.0%, respectively; P = 0.488). Posthoc nonparametric testing demonstrated significant differences favoring the total (P = 0.044) and 30-minute NGX-4010 groups (P = 0.035). Significantly, more patients in the total and 30-minute NGX-4010 group felt improved on the patient global impression of change versus control (67% vs. 55%, P = 0.011 and 65% vs. 45%, P = 0.006, respectively). Mild to moderate transient application site pain and erythema were the most common adverse events. CONCLUSIONS: Although the primary endpoint analyses were not significant, trends toward pain improvement were observed after a single 30-minute NGX-4010 treatment. PMID- 22067663 TI - Interpretation of genotypic resistance to predict darunavir/ritonavir failure in antiretroviral experienced patients. AB - From the Italian Antiretroviral Resistance Cohort Analysis database, 1104 patients starting ritonavir-boosted darunavir-containing regimen were included as follows: 118 subsequently failed treatment at a median of 11 months (interquartile range: 5-20); 3 years failure proportion: 24.6%. HIV Drug Resistance Database and ANRS interpretation algorithms were associated with a progressive risk prediction of virological failure at adjusted Cox. In contrast, Rega algorithm allows to identify a higher number of patients at risk of failure, without losing statistical significance. Four mutations (V32I, I50V, L76V, I84V) were predictive of failure, the hazard ratio progressively increased by detecting 1 (hazard ratio: 2.0, 95% confidence interval: 1.3 to 3.0), 2 (3.6, 2.0 to 6.6), or 3 of them (9.7, 2.8 to 33.5). PMID- 22067664 TI - Rapamycin with antiretroviral therapy in AIDS-associated Kaposi sarcoma: an AIDS Malignancy Consortium study. AB - PURPOSE: The mammalian target of rapamycin is activated in Kaposi sarcoma (KS) and its inhibitor, rapamycin, has induced KS regression in transplant-associated KS. This study aimed to evaluate rapamycin's safety and toxicity in HIV-infected individuals with KS receiving antiretroviral therapy (ART), investigate rapamycin interactions with both protease inhibitor (PI)-containing and nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing ART regimens, and assess clinical and biological endpoints including KS response and mammalian target of rapamycin-dependent signaling. METHODS: Seven participants, 4 on PI-based and 3 on NNRTI-based ART, had rapamycin titrated to achieve trough concentrations of 5 10 ng/mL. Patients were monitored for safety and KS response. KS biopsies were evaluated for changes in phosphoribosomal S6 protein, and phospho-Akt expression. Interleukin 6 and vascular endothelial growth factor levels, HIV and KS associated herpesvirus viral loads, and CD4 counts were monitored. RESULTS: Despite pharmacokinetic interactions resulting in >200-fold differences in cumulative weekly rapamycin doses between participants on PI-containing and NNRTI containing regimens, treatment was well tolerated. There were no significant changes in viral loads or cytokine levels; modest initial decreases in CD4 counts occurred in some patients. Three participants, all on PI-containing regimens and with higher rapamycin exposure, showed partial KS responses. Three of 4 subjects whose biopsies were studied at >=day 50 showed decreased phosphoribosomal S6 protein staining. CONCLUSIONS: Rapamycin seems safe in HIV-infected individuals with KS and can, in some cases, induce tumor regression and affect its molecular targets. Significant pharmacokinetic interactions require careful titration to achieve target drug trough concentrations but may be exploited to achieve therapeutic benefit. PMID- 22067665 TI - Outcomes of antiretroviral treatment programs in rural Southern Africa. AB - BACKGROUND: Data on outcomes of antiretroviral treatment (ART) programs in rural sub-Saharan African are scarce. We describe early losses and long-term outcomes in 6 rural programs in Southern Africa with limited access to viral load monitoring and second-line ART. METHODS: Patients aged >=16 years starting ART in 2 programs each in Zimbabwe, Mozambique, and Lesotho were included. We evaluated risk factors for no follow-up after starting ART and mortality and loss to follow up (LTFU) over 3 years of ART, using logistic regression and competing risk models. Odds ratios and subdistribution hazard ratios, adjusted for gender, age category, CD4 category, and World Health Organization stage at start of ART are reported. RESULTS: Among 7725 patients, 449 (5.8%) did not return after initiation of ART. During 9575 person-years, 698 (9.6%) of those with at least 1 follow-up visit died, and 1319 (18.1%) were LTFU. At 3 years, the cumulative incidence of death and LTFU were 12.5% (11.5%-13.5%) and 25.4% (24.0%-26.9%), respectively, with important differences between countries as follows: in Zimbabwe 75.1% (72.8%-77.3%) were alive and on ART at 3 years compared with 55.4% (52.8%-58.0%) in Lesotho and 51.6% (48.0%-55.2%) in Mozambique. In all settings, young age and male gender predicted LTFU, whereas advanced clinical stage and low baseline CD4 counts predicted death. CONCLUSIONS: In African ART programs with limited access to second-line treatment, mortality, and LTFU are high in the first 3 years of ART. Low retention in care is a major threat to the sustainability of ART delivery in Southern Africa, particularly in rural sites. PMID- 22067667 TI - Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis. AB - Genotypic and phenotypic characterization was performed of HIV-1 isolates from treatment-naive HIV-1-infected patients experiencing virologic failure (VF) during treatment with the nonnucleoside reverse transcriptase inhibitor (NNRTIs) rilpivirine or efavirenz in the pooled phase 3 studies ECHO and THRIVE. Among 686 patients receiving rilpivirine, 72 (10%) experienced VF versus 39 of 682 (6%) receiving efavirenz. In patients with low baseline viral load (VL) <=100,000 copies per milliliter, the proportions of rilpivirine VFs (19 of 368) and efavirenz VFs (16 of 330) were the same (5%). In patients with high baseline VL >100,000 copies per milliliter, the proportion of VFs was higher with rilpivirine (53 of 318; 17%) than efavirenz (23 of 352; 7%). The rate of rilpivirine VF was comparable between HIV-1 subtype B-infected (11%) and nonsubtype B-infected (8%) patients. The absolute number of VFs with treatment-emergent NNRTI resistance associated mutations (RAMs) was higher for rilpivirine (most commonly E138K or K101E) than efavirenz (most commonly K103N), but relative proportions were similar [63% (39 of 62) vs. 54% (15 of 28), respectively]. More rilpivirine VFs had treatment-emergent nucleoside/nucleotide reverse transcriptase inhibitor RAMs than efavirenz VFs [68% (42 of 62) versus 32% (9 of 28), respectively], most commonly M184I and M184V. The proportion of rilpivirine VFs with RAMs in patients with low baseline VL was lower than in those with high baseline VL [38% (6 of 16) versus 72% (33 of 46) for NNRTI RAMs and 44% (7 of 16) versus 76% (35 of 46) for nucleoside/nucleotide reverse transcriptase inhibitor RAMs, respectively]. In summary, VF and treatment-emergent reverse transcriptase RAMs were similar at low baseline VL but more frequent at high baseline VL in rilpivirine-treated than in efavirenz-treated patients. The frequent emergence of E138K, especially in combination with M184I, in rilpivirine VFs is a unique finding of these trials. PMID- 22067666 TI - Measurement of mucosal biomarkers in a phase 1 trial of intravaginal 3% StarPharma LTD 7013 gel (VivaGel) to assess expanded safety. AB - OBJECTIVE: The aim of this study was to examine the effect of the 3% StarPharma LTD 7013 gel (VivaGel) on mucosal immune markers hypothesized to be associated with HIV-1 acquisition. DESIGN: Phase 1, placebo-controlled, randomized, double blind clinical trial was performed in 54 young women in the United States and Kenya. Participants used carbopol gel with and without (placebo) StarPharma LTD 7013 twice daily over 14 days. Cervical specimens were collected for cytokines, chemokines, T cells, and dendritic cells at days 0, 7, 14, and 21. A negative binomial regression model was used to assess differences between study arms. RESULTS: Several mucosal immune parameters were increased in the VivaGel arm compared with placebo. For cytokines D7, IL-6 (P = 0.05); D 14, interferon gamma (P = 0.03), IL-2 (P = 0.04), IL-5 (P = 0.003), and IL-10 (P = 0.001) were increased. On D7, CD8+/CD69+ T cells tended to be increased (P < 0.08); limiting analysis to visits without blood or bacterial vaginosis, these findings were stronger as follows: at D7, CD8+/CD69+ T cells were increased in the VivaGel arm (P < 0.005), as were CD4+/CD69+ cells (P = 0.001) and CD4+/CCR5+ T cells (P = 0.01). The changes described for D7 and 14 were no longer seen at D21. CONCLUSIONS: Markers associated with inflammation and epithelial damage were reversibly elevated in the VivaGel arm compared with the placebo arm after 7-14 days of twice daily product use. PMID- 22067668 TI - Cell phone-based and internet-based monitoring and evaluation of the National Antiretroviral Treatment Program during rapid scale-up in Rwanda: TRACnet, 2004 2010. AB - BACKGROUND: Monitoring and evaluation of antiretroviral treatment (ART) scale-up has been challenging in resource-limited settings. We describe an innovative cell phone-based and internet-based reporting system (TRACnet) utilized in Rwanda. METHODS: From January 2004 to June 30, 2010, all health facilities with ART services submitted standardized monthly aggregate reports of key indicators. National cohort data were analyzed to examine trends in characteristics of patients initiating ART and cumulative cohort outcomes. Estimates of HIV-infected patients eligible for ART were obtained from Joint United Nations Program on HIV/AIDS (Estimation and Projection Package-Spectrum, 2010). RESULTS: By June 30, 2010, 295 (65%) of 451 health centers, District and referral hospitals provided ART services; of these, 255 (86%) were located outside Kigali, the capital. Cell phone-based and internet-based reporting was used by 253 (86%) and 42 (14%), respectively. As of June 30, 2010, 83,041 patients were alive on ART, 6171 (6%) had died, and 9621 (10%) were lost-to-follow-up. Of those alive on ART, 7111 (8.6%) were children, 50,971 (61.4%) were female, and 1823 (2.2%) were on a second-line regimen. The proportion of all patients initiating ART at World Health Organization clinical stages 3 and 4 declined from 65% in 2005 to 27% in 2010. National ART coverage of eligible patients increased from 13% in 2005 to 79% in 2010. CONCLUSIONS: Rwanda has successfully expanded ART access and achieved high national ART coverage among eligible patients. TRACnet captured essential data about the ART program during rapid scale-up. Cell phone-based and internet-based reporting may be useful for monitoring and evaluation of similar public health initiatives in other resource-limited settings. PMID- 22067670 TI - Curcumin-supplemented yoghurt improves physiological and biochemical markers of experimental diabetes. AB - We investigated the effects of prolonged treatment of diabetic rats with curcumin supplemented yoghurt on the physiological and biochemical changes associated with diabetes mellitus. An established metabolic cage model was used to assess these changes in three groups of streptozotocin-diabetic rats which had been administered, by gavage, curcumin blended into yoghurt in the doses of 30, 60 and 90 mg/kg body weight (BW) per d (groups DC30, DC60, DC90) for 31 d. One group of non-diabetic rats was also treated with 90 mg/kg BW per d curcumin (NDC90). Three control groups of diabetic animals received water (DW), yoghurt (DY) and insulin at 27.78 MUmol/d by subcutaneous injection (DI). Also, two groups of non-diabetic animals received water (NDW) and yoghurt (NDY). Groups DI and DC90 exhibited significant falls, relative to DW and DY, in food and water intake, urine volume, glycaemia, urinary urea and glucose, proteinuria, serum TAG and activities of aspartate and alanine aminotransferases, and higher hepatic glycogen and BW. These improvements were greater in DI than in DC90. No difference was observed in the serum levels of total cholesterol or HDL-cholesterol, or in the masses of adipose and muscular tissues, between DC90 and DW or DY. Moreover, the improvements in curcumin-treated rats, relative to DW and DY, were significant and dose-dependent. The NDC90 group also showed no difference from the NDW or NDY groups, in any of the markers for diabetes. In conclusion, curcumin mixed into yoghurt at the highest dose tested exhibited anti-diabetic activity, improving significantly most of the markers assessed in this study. PMID- 22067669 TI - The GABA(A) receptor agonist THIP ameliorates specific behavioral deficits in the mouse model of fragile X syndrome. AB - Hyperactivity, hypersensitivity to auditory stimuli, and exaggerated fear are common behavioral abnormalities observed in individuals with fragile X syndrome (FXS), a neurodevelopmental disorder that is the most common genetic cause of autism. Evidence from studies of the Fmr1 knockout (KO) mouse model of FXS supports the notion that impaired GABAergic transmission in different brain regions such as the amygdala, striatum or cerebral cortex is central to FXS behavioral abnormalities. This suggests that the GABAergic system might be an intriguing target to ameliorate some of the phenotypes in FXS. Our recent work revealed that THIP (gaboxadol), a GABA(A) receptor agonist, can restore principal neuron excitability deficits in the Fmr1 KO amygdala, suggesting that THIP may also restore some of the key behavioral abnormalities in Fmr1 KO mice. Here, we reveal that THIP significantly attenuated hyperactivity in Fmr1 KO mice, and reduced prepulse inhibition in a volume-dependent manner. In contrast, THIP did not reverse the deficits in cued fear or startle response. Thus, this study shows that enhancing GABAergic transmission can correct specific behavioral phenotypes of the Fmr1 KO mouse further supporting that targeting the GABAergic system, and specifically tonic inhibition, might be important for correcting or ameliorating some key behaviors in FXS. PMID- 22067671 TI - Statistical learning methods as a preprocessing step for survival analysis: evaluation of concept using lung cancer data. AB - BACKGROUND: Statistical learning (SL) techniques can address non-linear relationships and small datasets but do not provide an output that has an epidemiologic interpretation. METHODS: A small set of clinical variables (CVs) for stage-1 non-small cell lung cancer patients was used to evaluate an approach for using SL methods as a preprocessing step for survival analysis. A stochastic method of training a probabilistic neural network (PNN) was used with differential evolution (DE) optimization. Survival scores were derived stochastically by combining CVs with the PNN. Patients (n = 151) were dichotomized into favorable (n = 92) and unfavorable (n = 59) survival outcome groups. These PNN derived scores were used with logistic regression (LR) modeling to predict favorable survival outcome and were integrated into the survival analysis (i.e. Kaplan-Meier analysis and Cox regression). The hybrid modeling was compared with the respective modeling using raw CVs. The area under the receiver operating characteristic curve (Az) was used to compare model predictive capability. Odds ratios (ORs) and hazard ratios (HRs) were used to compare disease associations with 95% confidence intervals (CIs). RESULTS: The LR model with the best predictive capability gave Az = 0.703. While controlling for gender and tumor grade, the OR = 0.63 (CI: 0.43, 0.91) per standard deviation (SD) increase in age indicates increasing age confers unfavorable outcome. The hybrid LR model gave Az = 0.778 by combining age and tumor grade with the PNN and controlling for gender. The PNN score and age translate inversely with respect to risk. The OR = 0.27 (CI: 0.14, 0.53) per SD increase in PNN score indicates those patients with decreased score confer unfavorable outcome. The tumor grade adjusted hazard for patients above the median age compared with those below the median was HR = 1.78 (CI: 1.06, 3.02), whereas the hazard for those patients below the median PNN score compared to those above the median was HR = 4.0 (CI: 2.13, 7.14). CONCLUSION: We have provided preliminary evidence showing that the SL preprocessing may provide benefits in comparison with accepted approaches. The work will require further evaluation with varying datasets to confirm these findings. PMID- 22067674 TI - Shifting mindsets: work in progress. AB - The past few months have seen a hive of activity related to the publishing of reports and documents in the UK. July heralded the arrival of the long-awaited final report on the Palliative Care Funding Review (Hughes-Hallett et al, 2011). PMID- 22067673 TI - Adjuvant hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin after curative resection of hepatocellular carcinoma. AB - OBJECTIVES: We investigated whether adjuvant hepatic arterial infusional chemotherapy (HAIC) with 5-fluorouracil (5-FU) and cisplatin reduces the recurrence of hepatocellular carcinoma (HCC) after curative resection. METHODS: Between January 2006 and December 2008, 31 HCC patients received four cycles of adjuvant HAIC with 5-FU and cisplatin via port system after curative resection. During the same period, 62 patients, who did not take any adjuvant therapy, were selected as controls. RESULTS: Tumor characteristics, such as distribution of TNM stage, pathologic differentiation, portal vein invasion, or microscopic invasion did not differ between control and adjuvant groups. During follow-up, recurrence developed in 11 adjuvant (35.5%) and 24 control patients (38.7%; p = 0.823). Tumor progression after recurrence was the cause of death in 2 adjuvant (28.6%) and 7 control patients (38.8%; p = 0.912). The 2-year recurrence rate was 9.1% in the adjuvant group and 4.2% in the control group, with the median recurrence-free survival time being 10.5 and 7.5 months, respectively (p = 0.324). The 3-year cumulative survival rate was 73.3% in the adjuvant group and 68.3% in the control group (p = 0.355). CONCLUSION: Adjuvant HAIC with 5-FU and cisplatin did not offer any beneficial effect on the recurrence after curative resection of HCC. PMID- 22067675 TI - Transferring service provision from a Primary Care Trust to a charity: what needs to be considered? AB - On 1 April 2011, specialist palliative care (SPC) services in NHS Berkshire West transferred to Sue Ryder, a third sector provider of health and social care in the UK. Prior to the transfer, Berkshire West Primary Care Trust (PCT) commissioned services from its own provider arm and from Sue Ryder's Nettlebed Hospice in South Oxfordshire. PMID- 22067676 TI - Advance directives: Portuguese palliative care professionals' views. AB - Advance directives are a controversial subject in Portugal at present, particularly among health professionals. Although some health professionals consider them to be important tools that are helpful in making proper decisions and promoting patient autonomy, others think that they may interfere with the human and relational dimension of care. It is therefore timely to investigate health professionals' views of advance directives in more detail. This study aimed to identify and reflect on Portuguese palliative care professionals' perspectives of advanced directives and their relevance to end-of-life decision making. A qualitative exploratory methodology was adopted in which interviews were conducted with two physicians, six nurses, two psychologists, and one social worker from four palliative care teams based across Portugal. The findings emphasize the relevance of advance directives to ethical decision-making processes in palliative care. However, debates are needed regarding whether advance directives should be legally binding. PMID- 22067677 TI - Symptom experience and management among people with acute myeloid leukaemia in Thailand. AB - In Thailand, haematological malignancy is one of the most common types of cancer. This cross-sectional study, conducted in Southern Thailand, aimed to describe the symptom experiences of and symptom management strategies among patients with acute myeloid leukaemia (AML). Sixty hospitalized patients with AML were recruited. The Symptom Experience Scale and two open-ended questions regarding symptom-management strategies were used to collect data via face-to-face interviews 2 weeks after the induction phase of the AML protocol. The data was analysed using descriptive statistics and content analysis. High fever, weakness, nausea, and anorexia were the four most prevalent symptoms reported. Other prevalent symptoms included weight loss, bleeding, nausea and vomiting, dysphagia, and a cluster of psycho-emotional symptoms: worrying, fear, feeling discouraged, and feeling bored. Patients used various approaches and strategies to alleviate their symptoms, which could be categorized into five groups: preventive, direct, distraction, complementary, and restorative approaches. This study has provided important information for the development of symptom management nursing programmes for patients with AML, particularly in Thailand. PMID- 22067678 TI - Development and evaluation of the Pain Assessment in the Communicatively Impaired (PACI) tool: part I. AB - Pain is a common symptom for long-term care residents, particularly those in need of palliative care. However, pain assessment in residents who have communication limitations is challenging. A study was conducted with the aim of developing a pain assessment tool that could feasibly be used by direct care providers in long term care with minimal training yet demonstrating strong psychometric properties. The study used both qualitative and quantitative methods to develop and test the Pain Assessment in the Communicatively Impaired (PACI) tool. Part I of this paper reports on the development phase; a forthcoming second part will report on the testing phase. The overall results of this study support the psychometric properties and feasibility of the PACI tool, offering preliminary support for its use in clinical practice. PMID- 22067679 TI - Nursing interventions to promote dignified dying in South Korea. AB - PURPOSE: This descriptive study aimed to assess the appropriateness of the International Classification for Nursing Practice (ICNP) catalogue Palliative Care for Dignified Dying for palliative care nursing interventions in South Korea. METHODS: The study surveyed 213 South Korean nurses who might regularly care for dying patients. Nurses were recruited to complete a survey that included interventions from the ICNP catalogue listed with Likert response sets. FINDINGS: All of the interventions were scored as being at least 'slightly important' on average. The following three nursing interventions were ranked as most important when caring for dying patients: establish trust, establish rapport, and administer pain medication. CONCLUSIONS: The study provides new insights into the palliative care provided in South Korea by documenting nurses' views of what are the most important palliative care nursing interventions. It also suggests that the palliative care interventions listed in the ICNP catalogue Palliative Care for Dignified Dying are in congruence with the interventions that nurses in South Korea use. PMID- 22067680 TI - Challenges in home-based palliative care in Norway: a qualitative study of spouses' experiences. AB - INTRODUCTION: Issues around patients' preferred place of care and death are taking greater precedence of late. However, little is known about patients' and carers' experiences of palliative care in the home setting. This study explored carers' views of what determines the quality of home care at the end of life. METHODS: The study made use of systems theory, the purpose of which is to obtain a broad understanding of a phenomenon by looking at the relations between its individual elements. Seven carers (spouses) of people who died having received home-based palliative care in three different municipalities in Norway were interviewed. RESULTS: None of the participants had planned to give or receive palliative care in the home. However, they did not regret that the home had been the place of care. Factors deemed important to acheiving the best possible home based palliative care included around-the-clock help, holistic care, and affirmation of the significance of the carer's role. CONCLUSION: Health professionals should be more forthcoming in discussing the benefits and challenges of home-based palliative care and make greater acknowledgment of the carer's role. Treatment plans may be helpful in acheiving these goals. PMID- 22067681 TI - End of life in an Icelandic nursing home: an ethnographic study. AB - AIM: To examine care of the dying elderly in a nursing home in Iceland. METHODS: An ethnographic study design was adopted. The study sample comprised all of the nursing home residents, their relatives, and all of the staff working in the nursing home, but with a particular focus on the 11 registered nurses (RNs) on the site. Data was collected through participant observation, semi-structured group interviews with the RNs, and an examination of the nursing home's official records. Underlying themes were discovered using interpretative phenomenology. FINDINGS: Two main themes emerged: that palliative care is the most important element of care in the home, and that RNs are the pillars of caring for the dying elderly in the nursing home. CONCLUSIONS: The findings suggest that RNs' professional knowledge can greatly contribute to the care of dying elderly residents in nursing homes. There seem to be many parallels between the condition and wellbeing of very frail nursing home residents and patients in specialized palliative care units for the elderly. Public awareness of palliative care of the elderly in Icelandic nursing homes should be encouraged. PMID- 22067682 TI - Politics and palliative care: China (part II). PMID- 22067683 TI - Diazepam-induced decrease in anxiety-like behaviors of marmoset monkeys exposed to a novel open-field. AB - Unfamiliar environments can be a source of stress, fear and anxiety for marmoset monkeys. In spite of existing data, the influence of putative anxiolytics on the effects of novel environments has yet to be tested in primates. Therefore, the behavior of adult black tufted-ear marmosets to a single brief (15 min) exposure to a novel environment was analyzed in the presence and absence of diazepam (DZP). Marmosets were pre-treated with vehicle (n=5) or diazepam (0.5 mg/kg, ip; n=5) and submitted to a 15 min free exploration trial within a rectangular open field arena. DZP-treated subjects, compared to vehicle controls, demonstrated significantly lower rates of (phee) contact calls and exploration, while a higher scan duration. Sojourn time in the arena's central zone was also significantly higher in the former group and sedation was not observed. Thus, pre-treatment with the benzodiazepine DZP decreased several anxiety-related behaviors induced by subjecting the marmosets to a new environment. The results also indicate that, as with rodent subjects, the open-field may provide a useful simple paradigm for assessing anxiety-like behaviors in this primate and, as such, constitutes a unique opportunity for direct comparative studies between rodents and marmoset monkeys in terms of anxiety and/or sedation. PMID- 22067684 TI - Chinese women's sexuality concerns after gynecologic cancer. AB - BACKGROUND: Sexuality has been recognized as an integral aspect of quality of life. Issues surrounding sexuality have also been acknowledged to have a great impact on the quality of life of gynecologic cancer patients. OBJECTIVES: The objectives of this study were to describe sexual function and sexual activity among Chinese women after gynecologic cancer and to identify significant predicting factors of women's sexuality outcome changes. METHODS: This is a descriptive correlational study that was performed in mainland China. A sexuality scale was used to assess women's sexuality outcomes. RESULTS: A total of 156 Chinese women who had gynecologic cancer were included in this study. Study results revealed that sexual dysfunction was an important concern among these women (62.2%). The rate of sexual inactivity (70.5%) was relatively high. Reasons for sexual inactivity were related to worry about possibly weakening the potency of treatment (46.5%), fear of cancer recurrence (41.1%), and lack of sexual interest (31%). When looking at predictors of negative changes of women's sexuality after cancer, this study found that older age (>50 years old) was associated with the decrease of sexual desire/interest (odds ratio, 3.64; confidence interval, 1.19-11.16). Women who received radiation therapy had more severe vaginal dryness (odds ratio, 2.27; confidence interval, 1.10-4.72) and were less sexually active than those who did not have radiation therapy. CONCLUSION: Chinese women after gynecologic cancer suffered from various sexuality concerns. IMPLICATIONS FOR PRACTICE: Considering the high rates of sexual dysfunction and sexual inactivity, there is a need to integrate sexuality into routine nursing care. PMID- 22067685 TI - Male caregivers of patients with breast and gynecologic cancer: experiences from caring for their spouses and partners. AB - BACKGROUND: There is considerable evidence demonstrating the negative effects of caregiving particularly in the areas of psychological well-being and quality of life of family caregivers of patients with cancer. However, there is little work on male caregivers' subjective experience of caring for family members with cancer, and little is known on how caregivers experience the caring over time. OBJECTIVE: The objective of the study was to explore male spouses'/partners' experience of caring for their wives/partners with breast and gynecologic cancer over a 1-year period. METHOD: An exploratory longitudinal qualitative descriptive design using face-to-face interviews of 15 spouses/partners was used in this study. Content analysis of the transcribed data was conducted to extract significant categories and themes. RESULTS: Varying degrees of interrelated cognitive, physical, and psychological impact were experienced by caregivers that extended to 12 months. Gender-specific attitudes prevented male caregivers from supporting their own self. Male caregivers dealt with problems that arose in the caregiving congruent with their masculinity, such as minimizing disruptions, focusing on tasks, and keeping their own stress to themselves. CONCLUSION: Male caregivers as a separate group with their own needs have not received much attention in the cancer literature, and their concerns and challenges may differ from those of female caregivers. IMPLICATIONS FOR PRACTICE: Male caregivers' concerns and challenges must be taken into consideration when planning appropriate interventions to support them in their caregiving role. PMID- 22067688 TI - Factors associated with self-care self-efficacy among gastric and colorectal cancer patients. AB - BACKGROUND: Many studies have demonstrated that self-efficacy plays a crucial role in self-care. However, findings from previous studies indicate that the relationships between self-efficacy and several variables are inconsistent. OBJECTIVE: The purpose of this study was to assess the level of self-care self efficacy among Chinese gastric and colorectal cancer patients and to identify the demographic and disease-related, physical, psychological, and social factors associated with their self-care self-efficacy. METHODS: One hundred forty-eight cancer patients were recruited from hospitals in Shanghai and Shandong Province. Their self-efficacy, health status, social support, and mental health were assessed during face-to-face interview, using the Strategies Used by People to Promote Health (Chinese version), Medical Outcome Study Short Form 36, Social Support Questionnaire, and the Hospital Anxiety and Depression Scale. RESULTS: The overall level of self-care self-efficacy was moderate (mean, 80.34). The multiple regression analyses indicated that depression, physical functioning, use of available social support, vitality, and profession were indicators of the level of self-care self-efficacy and accounted for 60.9% of the variances. CONCLUSION: Participants who had less depression, better physical function, more social support, and higher vitality tended to have higher levels of self-care self-efficacy. Depression levels had the largest influence on self-care self efficacy. IMPLICATIONS FOR PRACTICE: Findings indicate that nurses may be able to influence certain cancer patients' self-care self-efficacy by attending to depression and other variables related to physical and social functioning. PMID- 22067686 TI - Smoking cessation in hospital workers: effectiveness of a coordinated program in 33 hospitals in Catalonia (Spain). AB - BACKGROUND: The Catalan Network of Smoke-free Hospitals coordinates a smoking cessation program addressed to hospital workers. The program included training in tobacco cessation, a common software, and free access to pharmacological treatments. OBJECTIVE: This study aimed to evaluate the effectiveness of the Catalan Network of Smoke-free Hospitals smoking cessation program for abstinence among workers of the 33 participating hospitals. METHODS: A total of 930 hospital workers (in 33 hospitals) attended the cessation units between July 2005 and December 2007. The program included active follow-up during 6 months after quitting. We calculated 6-month abstinence probabilities by means of Kaplan-Meier curves according to gender, age, years of tobacco consumption, profession, Fagerstrom Test for Nicotine Dependence (FTND) score, and use of pharmacotherapy. RESULTS: Overall abstinence probability was 0.504 (95% confidence interval [CI]: 0.431-0.570) at 6 months of follow-up. Abstinence was higher in men (0.526, 95% CI = 0.398-0.651) than in women (0.495, 95% CI = 0.410-0.581). Physicians had higher abstinence (0.659, 95% CI = 0.506-0.811) than nurses (0.463, 95% CI = 0.349-0.576). Workers with high nicotine dependence (FTND > 7) had lower abstinence probability (0.376, 95% CI = 0.256-0.495) than workers, with FTND score equal or below 6 (0.529, 95% CI = 0.458-0.599). We observed the highest abstinence probabilities in workers treated with combined pharmacotherapy (0.761, 95% CI = 0.588-0.933). CONCLUSION: Significant predictors of abstinence were smoking 10 to 19 cigarettes/day, having present low or medium FTND score, and using combined treatment (nicotine replacement therapy and bupropion). IMPLICATIONS FOR PRACTICE: The results show the feasibility and success of a smoking cessation program for hospital workers coordinated at the regional level. PMID- 22067687 TI - Changes in siblings after the death of a child from cancer. AB - BACKGROUND: Few studies have examined changes in siblings after the death of a brother or sister, particularly from mother, father, and sibling perspectives within the first year after death. OBJECTIVE: This descriptive study identified and assessed the frequency of changes in siblings after a child's death from cancer. METHODS: Participants were recruited from cancer registries at 3 hospitals in the United States and Canada 3 to 12 months after the child's death. Thirty-six mothers, 24 fathers, and 39 siblings from 40 families were included. Semistructured interviews using open-ended questions were conducted with each parent and sibling separately in the home. Content analysis identified emerging themes, and the McNemar tests compared frequencies between each paired set of reports (sibling vs mother, sibling vs father, mother vs father). RESULTS: Sixty nine percent of participants reported personal changes in siblings (eg, changes in personality, school work, goals/life perspective, activities/interests). Forty seven percent noted changes in siblings' relationships with family members and peers. Only 21% of participants reported no changes attributed to the death. Comparisons of frequencies across informants were not significant. CONCLUSIONS: Most siblings experienced changes in multiple areas of their lives after the death of a brother or sister to cancer. Some changes reflected siblings that were positively adapting to the death, whereas other changes reflected difficulties. IMPLICATIONS FOR PRACTICE: Our findings offer guidance to improve aftercare for bereaved siblings and their families. Additional research is needed to further delineate the needs of bereaved siblings and to develop strategies to promote adaptation to loss. PMID- 22067689 TI - Arab American women's lived experience with early-stage breast cancer diagnosis and surgical treatment. AB - BACKGROUND: Currently, limited literature addresses Arab American women's responses to the impact of breast cancer and its treatments. OBJECTIVE: The objective of the study was to understand the experience of being diagnosed with and undergoing surgical treatment for early-stage breast cancer among Arab American women. METHODS: A qualitative interpretive phenomenological research design was used for this study. A purposive sample of 10 Arab American women who were surgically treated for early-stage breast cancer in the United States was recruited. Data were collected using individual interviews and analyzed using the Heideggerian hermeneutical methodology. RESULTS: Arab American women accepted breast cancer diagnosis as something in God's hands that they had no control over. Although they were content with God's will, the women believed that the diagnosis was a challenge that they should confront. The women confronted this challenge by accessing the healthcare system for treatment, putting trust in their physicians, participating when able in treatment decisions, using religious practices for coping, maintaining a positive attitude toward the diagnosis and the treatment, and seeking information. CONCLUSION: Arab American women's fatalistic beliefs did not prevent them from seeking care and desiring treatment information and options when diagnosed with breast cancer. IMPLICATIONS FOR PRACTICE: It is important that healthcare providers encourage patients to express meanings they attribute to their illness to provide them with appropriate supportive interventions. They should also individually assess patients' decision making preferences, invite them to participate in decision making, and provide them with tailored means necessary for such participation without making any assumptions based on patients' ethnic/cultural background. PMID- 22067690 TI - Meaning in bone marrow transplant nurses' work: experiences before and after a "meaning-centered" intervention. AB - BACKGROUND: When a clinical culture emphasizes cure, as in bone marrow transplantation (BMT) services, BMT nurses commonly experience enormous stress when patients are suffering or dying. In this context, it is unclear what meanings BMT nurses experience in their work and how they find meaning and sustain hope, given conflicting responsibilities to patients. OBJECTIVE: This study aimed to explore BMT nurses' experiences of meaning and hope and the effects of a meaning-centered intervention (MCI) on these experiences using qualitative methodology. METHODS: Fourteen BMT nurses engaged in a 5-session MCI, with 7 members each participating in 2 groups. Semistructured qualitative interviews were conducted at 1 month before and after the intervention. Interpretive phenomenology guided data analysis. RESULTS: The BMT nurses in the Princess Margaret Hospital experienced meaning in their involvement with their patients' suffering. The MCI seemed to inspire participants to engage more with patients and their suffering. Three subthemes reflected this influence: (a) greater awareness of boundaries between their personal and professional involvement, (b) enhanced empathy from an awareness of a shared mortality, and (c) elevated hope when nurses linked patients' suffering with meaning. CONCLUSIONS: This study confirms that patients' suffering constitutes nurses' search for meaning and hope in their work. The MCI offers a way in which to actively support nurses in this process. IMPLICATIONS FOR PRACTICE: Nurses can learn to be more responsive to patients' suffering beyond limits of cure. A minimal intervention, such as the MCI, supports BMT nurses in finding positive personal meaning and purpose in their otherwise highly stressful work culture. PMID- 22067691 TI - Sense of coherence and need for support among long-term survivors of childhood cancer. AB - BACKGROUND: The concept of sense of coherence (SOC) may be applied to explain individuals' resources for dealing with the stressors confronted in daily life. Little is known about what impact cancer in childhood may have on the development of SOC. OBJECTIVE: The objectives of this study were to compare SOC between long term survivors of childhood cancer and a comparison group and to explore the need for current support among the survivors and the association between need for support and SOC. METHODS: Data were collected from 224 long-term survivors aged 18 to 37 years using the 13-item SOC scale and interviews. A matched comparison group (n = 283) randomly selected from the general population was included. RESULTS: There was no significant difference in the mean SOC score between the survivors and the comparison group. Twenty percent of the survivors reported a need for support, a need significantly predicted by a low SOC, as well as surgery and/or radiation treatment often in combination with chemotherapy. CONCLUSIONS: Long-term survivors of childhood cancer seem to have resources to cope with stressful situations in life to the same degree as people in general. Survivors with fewer resources to cope and those having received a more intense treatment were more likely to be in need of support. IMPLICATIONS FOR PRACTICE: The concept of SOC in nursing practice may be helpful to identify and discuss an individual's resources and impediments to health to better understand the need for support among survivors of childhood cancer. PMID- 22067692 TI - Comparing the meanings of fatigue in individuals with cancer in Thailand and Canada. AB - BACKGROUND: Illness is experienced in social contexts; its meaning is rooted in local beliefs and values as well as one's personal and family situation. Health professionals are steeped in knowledge of disease but know much less about illness. OBJECTIVES: The objective of the study was to learn more about the social construction of illness by comparing the meanings of fatigue in Thai and Canadian individuals with cancer. METHODS: Using an ethnoscience design, 10 Thai adults receiving chemotherapy for advanced lung cancer or colorectal cancer were interviewed twice. They were asked to sort words and phrases about fatigue from their first interview using Q-sort, triadic, and dyadic approaches; to name each pile; and to describe the similarities and differences between the piles. The card sorts were used to understand the relationships among key ideas in each interview. A table summarizing the card sorts was constructed, and patterns in the data were identified. RESULTS: Two segregates in the Thai data were identified: essential/constant and intermittent, with essential/constant including 2 segregates (feeble and altered cognition), and intermittent including 2 segregates (loss of mental strength and difficulty sleeping). The primary meanings of fatigue in the Thai data were related to temporality, whereas the primary meanings of fatigue in the Canadian data were related to the location of the fatigue (mind/body). CONCLUSION: These findings help us understand the social construction of fatigue, a common symptom in cancer. IMPLICATIONS FOR PRACTICE: Further research in relation to links between fatigue and other related-symptoms is needed with the goal of developing cross-cultural interventions for managing fatigue in the future. PMID- 22067693 TI - Invisibility: the lived experience of women with cancer of the vulva. AB - BACKGROUND: This study describes an exploration of the lived experience of 13 British women with cancer of the vulva who underwent surgical treatment. A review of the literature highlighted a paucity of knowledge as many studies were conducted during the 1980s and 1990s and investigated sexual functioning only. OBJECTIVE: An interpretive phenomenological approach based on the work of Heidegger and van Manen was used to frame the study by posing the question, "What must it be like to be diagnosed with, and have surgery for a cancer of the vulva?" METHODS: The women, younger than 50 years, were identified by purposive sampling and interviewed between 6 months and 5 years after surgery. The data were analyzed using framework analysis. RESULTS: The women's lived experience is described in its entirety by the concept of invisibility, characterized as something "no one can see," "heard of," and "talks about." CONCLUSIONS: The impact of this invisibility is discussed as the "invisibility of understanding" and "invisibility of support." IMPLICATIONS FOR PRACTICE: Although many women may expect to be cured of their vulval cancer, the invisible nature of the condition and the resulting lack of understanding and support may continue for a considerable period, as every aspect of their everyday life and in their relationships may be affected. The challenge now is to raise awareness of this condition and provide greater informational and emotional support for these women. PMID- 22067694 TI - Body image and its predictors in breast cancer patients receiving surgery. AB - BACKGROUND: Negative body image may reduce patients' ability to cope with breast cancer after surgery. OBJECTIVES: The purposes of this study were to (1) assess breast cancer patients' perceived level of symptom distress, anxiety, depression, disease impact, and body image and (2) evaluate factors associated with body image in breast cancer patients during the postoperative period. METHODS: A cross sectional and correlational design was used to collect data for this study, conducted in northern Taiwan. A set of questionnaires was used to measure body image, symptom distress, anxiety, depression, psychological impact of disease, and demographic and disease-related information. Stepwise regression was conducted to determine significant factors related to body image. RESULTS: Surgical procedure and age were found to be important factors related to body image concerns. Patient receipt of mastectomy and younger age were associated with greater body image concerns. CONCLUSION: The average age of breast cancer patients is declining in Taiwan, and body image problems in these patients are growing. Several factors are significantly related to body image distress among these patients. IMPLICATIONS FOR PRACTICE: By understanding variables associated with breast cancer patients' body image, health professionals can coordinate interventions to improve these women's body image. Among women with breast cancer, those who have received mastectomy and those who are younger are particularly vulnerable to body image concerns. Nursing assessment of body image indicators and implementation of strategies to increase self-confidence and self acceptance are needed for high-risk women. PMID- 22067695 TI - Demographics, cancer-related factors, and sexual function in rectal cancer patients in Taiwan: preliminary findings. AB - BACKGROUND: Sexual function has been ignored because survival issues associated with cancer treatment commonly take precedence over sexual issues. Sexual dysfunction remains a recognized complication after cancer treatment despite improvement in survival rates for patients with rectal cancer. OBJECTIVE: This study investigated the relationships among demographics (ie, age, gender, education, religion) and cancer-related factors (ie, stage of disease, type of treatment, time since operation, comorbid conditions) and sexual function in patients with rectal cancer. METHODS: A cross-sectional study with a convenience sample of 120 rectal cancer patients from a medical center in southern Taiwan completed the International Index of Erectile Function, Female Sexual Function Index, a demographic questionnaire, and medical data during face-to-face interviews. RESULTS: In both men and women, better sexual function was significantly associated with younger age but not with religion, time since operation, or number of chronic conditions. In men only, better sexual function was associated with earlier stage of cancer, fewer cancer treatments, and higher education. CONCLUSION: Sexual function may receive greater attention in Taiwan when rectal cancer patients receive appropriate care. A larger diverse sample is needed for further examination of sexual function over time. IMPLICATIONS FOR PRACTICE: Health promotion programs for long-term survivors should include a consistent assessment of sexual function before and after an operation, and patients should receive clinical sexual counseling. PMID- 22067696 TI - Effects of false-positive results in a breast screening program on anxiety, depression and health-related quality of life. AB - BACKGROUND: Decreased anxiety has been reported among women with false-positive results in mammography screening programs. No long-term effects have been fully demonstrated, and the findings for anxiety and depression are contradictory. Few studies have addressed changes in health-related quality of life (HRQOL). OBJECTIVE: The objective was to study the short- and long-term effects such as changes in anxiety, depression, and HRQOL among women with false-positive results. METHODS: With a longitudinal study design, data were collected on anxiety and depression (Hospital Anxiety and Depression Scale) and HRQOL (Short Form 36 [SF-36] Health Survey) among women with false-positive results before screening, at recall, and at 3 and 6 months after screening. Controls (negative results in screening) were measured before screening and at 6 months after. RESULTS: Women with false-positive results (n = 128) showed increased anxiety at recall (mean, 4.6 [SD, 3.7]) versus before screening (P = .04), but this decreased until 6 months after screening. Depression was increased until 6 months after screening (not statistically significant). Women with false-positive results scored lower than did control subjects on general health (P = .02) and mental health (P = .03) and higher on depression (P = .045) at 6 months after screening. CONCLUSIONS: Efforts should be made to minimize anxiety at recall and depression after screening. Further research is needed on the long-term effects of recall and any effects on HRQOL. IMPLICATIONS FOR PRACTICE: Information about the prevalence of false-positive results and time until unambiguous diagnostic results should be improved. Information leaflet based on evidence needs to be continually updated. PMID- 22067697 TI - Prognostic items for the last 10 and 3 days of life of cancer patients at home. AB - BACKGROUND: Prognostic indices are needed to optimize end-of-life care for cancer patients at home, but few prognostic indices predict the last 10 days. OBJECTIVE: The purpose of this study was to identify predictors for the last 10 and 3 days of life in patients with lung, gastric, or colorectal cancer at home. METHODS: Symptoms and signs were initially identified by literature review, and questionnaire was developed. Evaluation of these items and identification of additional items were then performed by 72 visiting nurses using the 3-round Delphi approach. RESULTS: The evaluation of 31 third-round responses is reported. The items for gastric and colorectal cancers were almost same; these cancers were treated as gastrointestinal cancer. To predict the last 10 and 3 days, there were 6 and 0 specific items for lung cancer, respectively, and 5 and 13 specific items for gastrointestinal cancer, respectively. There were 9 common items to predict the last 10 days and 29 common items to predict the last 3 days. CONCLUSION: The specific and common items that could be used to predict the last 10 and 3 days in patients with lung or gastrointestinal cancer were identified. The prognostic items for the last 3 days of life were more numerous among the gastrointestinal cancers than those for the last 10 days. IMPLICATIONS FOR PRACTICE: Specific prognostic items for each cancer are useful for visiting nurses to offer individualized care to patients and families. Using the specific and common prognostic items, end-of-life care may be improved. PMID- 22067698 TI - From "no big deal" to "losing oneself": different meanings of mastectomy. AB - BACKGROUND: Because of early detection and advanced treatment options, more women with breast cancer survive after mastectomy and thus have to face the choice of living with or without a reconstructed breast for many years to come. OBJECTIVE: This article investigates these women's narratives about the impact of mastectomy on their lives, as well as their reflections on breast reconstruction. METHODS: Fifteen women were strategically chosen from a previous population-based study on mastectomy. They were contacted for further exploration in thematic narrative inspired interviews 4.5 years after mastectomy. RESULTS: Three types of storylines were identified. In the first storyline, the mastectomy was described as "no big deal"; losing a breast did not disturb the women's view of themselves as women, and breast reconstruction was not even worth consideration. In the second storyline, the women described the mastectomy as shattering their identity. Losing a breast implied losing oneself as a sexual being, a woman, and a person. The third storyline fell in between the other two; the sense of femininity was wounded, but not to the extent that they felt lost as women. CONCLUSION: Our findings suggest that the experience of mastectomy due to breast cancer is very much individual and contextual. Losing a breast may be of minor or major importance. IMPLICATIONS FOR PRACTICE: Healthcare practitioners should be attentive to how the women themselves experience the personal meaning of losing a breast and guard against vague preconceptions based on the breast-sexuality femininity discourse and its connection to what the patient needs. PMID- 22067699 TI - Challenging the distal-to-proximal cannulation technique for administration of anticancer therapies: a prospective cohort study. AB - BACKGROUND: Distal-to-proximal technique has been recommended for anticancer therapy administration. There is no evidence to suggest that a 24-hour delay of treatment is necessary for patients with a previous venous puncture proximal to the administration site. OBJECTIVES: This study aims to identify if the practice of 24-hour delay between a venous puncture and subsequent cannulation for anticancer therapies at a distal site is necessary for preventing extravasation. METHODS: A prospective cohort study was conducted with 72 outpatients receiving anticancer therapy via an administration site distal to at least 1 previous venous puncture on the same arm in a tertiary cancer center in Australia. Participants were interviewed and assessed at baseline data before treatment and on day 7 for incidence of extravasation/phlebitis. RESULTS: Of 72 participants with 99 occasions of treatment, there was 1 incident of infiltration (possible extravasation) at the venous puncture site proximal to the administration site and 2 incidents of phlebitis at the administration site. CONCLUSION: A 24-hour delay is unnecessary if an alternative vein can be accessed for anticancer therapy after a proximal venous puncture. IMPLICATIONS FOR PRACTICE: Infiltration can occur at a venous puncture site proximal to an administration site in the same vein. However, the nurse can administer anticancer therapy at a distal site if the nurse can confidently determine that the vein of choice is not in any way connected to the previous puncture site through visual inspection and palpation. PMID- 22067700 TI - Impact of health information-seeking behavior and personal factors on preferred role in treatment decision making in men with newly diagnosed prostate cancer. AB - BACKGROUND: Prostate cancer (PC) patients continue to have unmet information needs at the time of diagnosis and are often unable to communicate their preferences to physicians at the time of the treatment consultation. OBJECTIVE: The objective of the study was to determine the impact of health information seeking behavior (HISB) and personal factors on patients' preferred role in treatment decision making (TDM). METHODS: Participants consisted of 150 men with newly diagnosed PC seen at 2 urology clinics in western Canada. A survey questionnaire was used to gather information on HISB, personal factors influencing treatment choice, and decision control. RESULTS: More than 90% of the participants reported a preference to play either an active or collaborative role in TDM and having either an "intense" or "complementary" HISB. No significant association was found between HISB and preferred role in TDM. Impact of treatment on survival and urinary function and the urologist's recommendation were identified as the 3 main factors influencing the treatment decision. CONCLUSIONS: At the time of diagnosis, the majority of men want to be involved in TDM and have access to information. Our findings suggest that the type and amount of information men want to access are dependent on HISB. Assessing factors having an impact on TDM may prove useful to guide patient-clinician treatment discussions. IMPLICATIONS FOR PRACTICE: This survey provides clinicians with a method to assess information and decision preferences of men with newly diagnosed PC and factors having an influence on treatment choice. PMID- 22067701 TI - High sero-prevalence of caseous lymphadenitis identified in slaughterhouse samples as a consequence of deficiencies in sheep farm management in the state of Minas Gerais, Brazil. AB - BACKGROUND: Caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis, is one of the most important diseases of sheep and goats, causing considerable economic losses for herd owners. RESULTS: We assessed the seroprevalence of infection with C. pseudotuberculosis in 805 sheep from 23 sheep farms that supply slaughterhouses in the state of Minas Gerais; we also analyzed management practices that could be associated with CLA occurrence, used on these and nearby farms that also supplied animals to the slaughterhouse (n = 60). The serum samples for assaying CLA infection were taken at the slaughterhouse. Frequency of infection with C. pseudotuberculosis was estimated at 43.7%, and farm frequency was estimated at 100%. Management practices were analyzed through a questionnaire. All farmers (60/60) had extensive/semi-extensive rearing system; 70.0% (42/60) identified sheep individually; 11.7% (7/60) had periodical technical assistance; 41.7% (25/60) disinfected the facilities; 86.7% (52/60) used barbed wire fences and did not implement adequate CLA control measures; only 11.7% (7/60) of breeders reported vaccination against C. pseudotuberculosis; 13.3% (8/60) took note of animals with clinical signs of CLA; 1.7% (1/60) opened and sanitized abscesses, and isolated the infected animals; 10.0% (6/60) knew the zoonotic potential of this disease and 1.7% (1/60) of the farmers culled animals in case of recurrence of abscesses. CONCLUSIONS: It can be concluded that C. pseudotuberculosis infection is widely spread in sheep flocks in Minas Gerais state in Brazil and that there is a lack of good management measures and vaccination, allowing transmission of this infectious agent throughout the production network. PMID- 22067702 TI - The effect of selenium enrichment on baker's yeast proteome. AB - The use of regular yeast (RY) and selenium-enriched yeast (SEY) as dietary supplement is of interest because the Nutritional Prevention of Cancer (NPC) trial revealed that SEY but not RY decreased the incidence of prostate cancer (PC). Using two-dimensional difference in gel electrophoresis (2D-DIGE)-tandem mass spectrometry (MS/MS) approach, we performed proteomic analysis of RY and SEY to identify proteins that are differentially expressed as a result of selenium enrichment. 2D-DIGE revealed 96 candidate protein spots that were differentially expressed (p<=0.05) between SEY and RY. The 96 spots were selected, sequenced by LC/MS/MS and 37 proteins were unequivocally identified. The 37 identified proteins were verified with ProteinProphet software and mapped to existing Gene Ontology categories. Furthermore, the expression profile of 5 of the proteins with validated or putative roles in the carcinogenesis process, and for which antibodies against human forms of the proteins are available commercially was verified by western analysis. This study provides evidence for the first time that SEY contains higher levels of Pyruvate Kinase, HSP70, and Elongation factor 2 and lower levels of Eukaryotic Translation Initiation Factor 5A-2 and Triosephosphate Isomerase than those found in RY. PMID- 22067703 TI - Phosphorylatable short peptide conjugated low molecular weight chitosan for efficient siRNA delivery and target gene silencing. AB - Small interfering RNA (siRNA) has been widely investigated as a potential therapeutic approach for diseases with genetic defects. However, its application was greatly hampered by the rapid degradation and poor cellular uptake. Recently, chitosan (CS) and its derivant have been considered as a promising siRNA transporter with the advantages of low toxicity, good biodegradability and biocompatibility. Chitosan of different molecular weight (Mw) and degrees of deacetylation (DD) showed significantly varied target gene silencing efficacy, and it is still not well clarified how these characteristics influence CS mediated siRNA transfection. To compare the aspects of cell permeability and intracellular unpacking of CS/siRNA complex on the effect of CS/siRNA transfection. A radiolabeled siRNA, targeting firefly luciferase gene, was loaded by chitosan of different molecular weight (varying from 2000 to 800,000 Da) and subjected to the transfection against MDA-MB-231/Luc human breast cancer cell line which stably expressed knocked in firefly Luciferase reporter gene. Following transfection intracellular radioactivity was measured to represent cell entrance ability of the CS/siRNA, while, luciferase activity in the cell lysate was also determined to reflect target gene silencing effect. The results revealed that although low molecular weight chitosan (LMWC) condensed siRNA has the highest cell permeability of almost two folds of medium molecular weight chitosan and lipofactamine, its target gene silencing effect is really low of almost eight times less than lipofectamine. This conspicuous contradiction gave us the hypothesis that LMWC generated more condensed CS/siRNA complex to facilitate cell entrance but the tight electrostatic interaction probably limited intracellular siRNA unpacking as well and unfavorably hindered target gene silencing as the final consequence. To approve this hypothesis a phosphorylatable short peptide conjugated LMWC was adopt to promote intracellular siRNA unpacking. Which was demonstrated of perfect target gene knock down ability to the extent of being even superior to lipofactamine 2000. In a conclusion, low molecular weight chitosan has the great potential to be an ideal siRNA vehicle if the issue of siRNA unpacking could be properly resolved. PMID- 22067704 TI - Effect of androstenedione on the growth and meiotic competence of bovine oocytes from early antral follicles. AB - Medium that contains 17beta-estradiol has been reported to support in vitro growth of bovine oocytes, isolated from early antral follicles, until the final stage. The aim of this study was to determine the effects of androstenedione in medium on such growing bovine oocytes. Oocyte-granulosa cell complexes were collected from early antral follicles and cultured for 14 days in medium supplemented with 17beta-estradiol (0, 10 and 100 ng/ml) or androstenedione (0, 10 and 100 ng/ml). The mean diameter of oocytes measured after seeding on the culture substrate was 96.9 MUm (n = 191). Either steroid was necessary for maintainance of the organization of oocyte-granulosa cell complexes over the 14 day culture period. In the 17beta-estradiol- or the androstenedione-supplemented medium about 80% or 65%, respectively, of viable oocytes were recovered. In both groups the increase in oocyte size was significant after 14 days. The in vitro grown oocytes were cultured for a further 22-24 h for oocyte maturation; 13% and 30% of oocytes grown in the 10 and 100 ng/ml 17beta-estradiol-supplemented medium reached metaphase II, respectively; more than 64% of oocytes grown in the androstenedione-supplemented medium matured to metaphase II. These results show that androstenedione, as 17beta-estradiol, can maintain the viability of bovine oocyte-granulosa cell complexes and support the growth of oocytes, and that androstenedione promotes the acquisition of oocyte meiotic competence efficiently at a low dose. PMID- 22067706 TI - Identifying weak linear features with the "coalescing shortest path image transform". AB - The detection of line-like features in images finds many applications in microanalysis. Actin fibers, microtubules, neurites, pilis, DNA, and other biological structures all come up as tenuous curved lines in microscopy images. A reliable tracing method that preserves the integrity and details of these structures is particularly important for quantitative analyses. We have developed a new image transform called the "Coalescing Shortest Path Image Transform" with very encouraging properties. Our scheme efficiently combines information from an extensive collection of shortest paths in the image to delineate even very weak linear features. PMID- 22067705 TI - Genetic bases of stuttering: the state of the art, 2011. AB - OBJECTIVE: The literature on the genetics of stuttering is reviewed with special reference to the historical development from psychosocial explanations leading up to current biological research of gene identification. SUMMARY: A gradual progression has been made from the early crude methods of counting percentages of stuttering probands who have relatives who stutter to recent studies using entire genomes of DNA collected from each participant. Despite the shortcomings of some early studies, investigators have accumulated a substantial body of data showing a large presence of familial stuttering. This encouraged more refined research in the form of twin studies. Concordance rates among twins were sufficiently high to lend additional support to the genetic perspective of stuttering. More sophisticated aggregation studies and segregation analyses followed, producing data that matched recognized genetic models, providing the final 'go ahead' to proceed from the behavior/statistical genetics into the sphere of biological genetics. Recent linkage and association studies have begun to reveal contributing genes to the disorder. CONCLUSION: No definitive findings have been made regarding which transmission model, chromosomes, genes, or sex factors are involved in the expression of stuttering in the population at large. Future research and clinical implications are discussed. PMID- 22067707 TI - The usefulness and feasibility of a screening instrument to identify psychosocial problems in patients receiving curative radiotherapy: a process evaluation. AB - BACKGROUND: Psychosocial problems in cancer patients are often unrecognized and untreated due to the low awareness of the existence of these problems or pressures of time. The awareness of the need to identify psychosocial problems in cancer patients is growing and has affected the development of screening instruments. This study explored the usefulness and feasibility of using a screening instrument (SIPP: Screening Inventory of Psychosocial Problems) to identify psychosocial problems in cancer patients receiving curative radiotherapy treatment (RT). METHODS: The study was conducted in a radiation oncology department in The Netherlands. Several methods were used to document the usefulness and feasibility of the SIPP. Data were collected using self-report questionnaires completed by seven radiotherapists and 268 cancer patients. RESULTS: Regarding the screening procedure 33 patients were offered to consult a psychosocial care provider (e.g. social worker, psychologist) during the first consultation with their radiotherapist. Of these patients, 31 patients suffered from at least sub-clinical symptoms and two patients hardly suffered from any symptoms. Patients' acceptance rate 63.6% (21/33) was high. Patients were positive about the content of the SIPP (mean scores vary from 8.00 to 8.88, out of a range between 0 and 10) and about the importance of discussing items of the SIPP with their radiotherapist (mean score = 7.42). Radiotherapists' perspectives about the contribution of the SIPP to discuss the different psychosocial problems were mixed (mean scores varied from 3.17 to 4.67). Patients were more positive about discussing items of the SIPP if the radiotherapists had positive attitudes towards screening and discussing psychosocial problems. CONCLUSIONS: The screening procedure appeared to be feasible in a radiotherapy department. In general, patients' perspectives were at least moderate. Radiotherapists considered the usefulness and feasibility of the SIPP generally to be lower, but their evaluations were mixed. A positive attitude to using screening instruments like the SIPP needs to be encouraged among radiotherapists, as this may not only improve the usefulness of a screening instrument, but also patients' satisfaction with care. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00859768. PMID- 22067708 TI - A self-propelled biological process: Plk1-dependent, product-activated feedforward mechanism. PMID- 22067709 TI - Essential protein interactions within the replisome regulate DNA replication. PMID- 22067710 TI - mTOR in podocyte function: is rapamycin good for diabetic nephropathy? PMID- 22067718 TI - Viscoelastic properties of confined molecular layers. AB - We study the viscoelastic properties of a film of n layers of spherical molecules confined between two walls. We find that the dynamic response arises from two competing contributions: the effective stiffness of n + 1 springs in series and softening due to strain fluctuations. In particular, the latter are the origin of the oscillatory behavior of the stiffness and the damping coefficient. The dissipation is strongest at the minima of the stiffness; the inverse behavior may occur for a modulated relaxation time. As a corollary we show that confined molecular layers cannot be described as Maxwell fluids. PMID- 22067717 TI - Colporrhaphy compared with mesh or graft-reinforced vaginal paravaginal repair for anterior vaginal wall prolapse: a randomized controlled trial. AB - OBJECTIVE: To report 2-year outcomes of a randomized controlled trial comparing standard anterior colporrhaphy with reinforced vaginal paravaginal repair using xenograft or synthetic mesh in women with symptomatic anterior vaginal wall prolapse. METHODS: Women with stage II or greater anterior prolapse were randomly assigned to three groups: anterior colporrhaphy, paravaginal repair with porcine dermis, or polypropylene mesh. Outcomes of prolapse stage, quality of life, degree of bother, and sexual symptoms were assessed by blinded examiners and validated measures at 2 years. Anatomic failure was defined as anterior prolapse at stage II or greater. Composite failure was defined as symptoms of "bulge" and anterior prolapse at stage II or greater. Power calculations determined 33 participants per arm would detect a 40% difference in anatomic success between standard and grafted repair. chi, Mann-Whitney U, and Student's t tests were used for comparisons. RESULTS: Of the 99 participants enrolled, 78 (79%) completed a minimum of 2-year follow-up. Those with mesh had a significantly lower anatomic failure rate (18%) than both the porcine (46%, P=.015) and colporrhaphy groups (58%, P=.002). All groups had statistically similar reductions in their prolapse and urinary symptom subscale scores. Composite failure was not statistically different between groups: 13% colporrhaphy, 12% porcine, and 4% mesh. Two reoperations for anterior prolapse occurred in the porcine group. Mesh erosion rates were 14% for the mesh group. CONCLUSION: Vaginal paravaginal repair with polypropylene mesh has the lowest anatomic failure rate when compared with that with xenograft and anterior colporrhaphy without differences in composite failures. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT0139171. LEVEL OF EVIDENCE: I. PMID- 22067716 TI - Effect of hysterectomy with ovarian preservation on ovarian function. AB - OBJECTIVE: To prospectively estimate the risk for earlier ovarian failure among women undergoing hysterectomy with ovarian preservation, as compared with women of similar age without hysterectomy. METHODS: A prospective cohort study was conducted among women aged 30 to 47 years undergoing hysterectomy without bilateral oophorectomy (n=406) and women with intact uteri (n=465). Blood samples and questionnaire data were obtained at baseline and annually for up to 5 years. Hazard ratios (HR) for ovarian failure, defined as follicle-stimulating hormone levels 40 international units/L or higher, were calculated using Cox proportional hazards models. RESULTS: Ovarian failure occurred among 60 of the women with hysterectomy and 46 of the women in the control group. Women undergoing hysterectomy were at nearly a twofold increased risk for ovarian failure as compared with women with intact uteri (HR 1.92, 95% confidence interval [CI] 1.29 2.86). The proportional hazards model further estimated that 14.8% of women with hysterectomies experienced ovarian failure after 4 years of follow-up compared with 8.0% of the women in the control group. Risk for ovarian failure was greater for women who had a unilateral oophorectomy along with their hysterectomy (HR 2.93, 95% CI 1.57-5.49), but also it was significantly increased for women who retained both ovaries (HR 1.74, 95% CI 1.14-2.65). CONCLUSION: Increased risk of earlier ovarian failure is a possible consequence of premenopausal hysterectomy. Although it is unresolved whether it is the surgery itself or the underlying condition leading to hysterectomy that is the cause of earlier ovarian failure, physicians and patients should take into account this possible sequela when considering options for treatment of benign conditions of the uterus. LEVEL OF EVIDENCE: II. PMID- 22067719 TI - Managing heart failure: a critical appraisal of the literature. AB - BACKGROUND: Preventing heart failure (HF) rehospitalizations requires examination of evidence-based research, which may lead to opportunities to improve on care transitions upon discharge from an acute care setting. This review was conducted to identify current literature in HF and disease management without focusing specifically on disease management programs. PURPOSE: The purpose of this study was to conduct a systematic review of the literature to better understand how to structure interventions for HF patients upon transition from the hospital to home and to outline critical research gaps. CONCLUSION: Patients recently hospitalized for HF or at high risk for HF decompensation should be considered for comprehensive heart failure disease management (HFDM) and/or structured HF interventions. Level 1 evidence demonstrated positive benefits from HFDM programs, structured telephone support, and telemonitoring interventions as an effective component of contemporary multidisciplinary HF management. CLINICAL IMPLICATIONS: Based on the evidence from this critique, key features and recommendations are provided. Also discussed is the State Action on Avoidable Rehospitalizations program, which may provide acute care centers in Massachusetts an opportunity to create an ideal transition home for HF patients. PMID- 22067721 TI - Effects of social support and stressful life events on health-related quality of life in coronary artery disease patients. AB - OBJECTIVE: The objective of this study was to examine the effects of social support and stressful life events on health-related quality of life (HRQoL) in coronary artery disease (CAD) patients. METHODS: Five hundred sixty consecutive patients with CAD attending cardiac rehabilitation program were invited to participate in the study. Data on stressful life events, perceived social support, and HRQoL were collected from the self-administered questionnaires, Social Readjustment Rating Scale, Multidimensional Scale of Perceived Social Support, and 36-Item Short Form Medical Outcome Questionnaire, respectively. RESULTS: In male patients, multivariate linear regression analyses revealed that physical domains of the HRQoL, specifically physical functioning, were associated with clinical aspects of the CAD, such as New York Heart Association class and angina pectoris class, and psychological domains of the HRQoL such as mental health, energy/vitality, and social functioning were associated with social characteristics such as stressful life events and perceived social support. In women, both physical and psychological domains of the HRQoL were associated only with social characteristics, especially with perceived social support. CONCLUSION: Perceived social support and stressful life events have independent significant effects on the HRQoL in CAD patients, especially in female patients. When planning cardiac rehabilitation programs, special attention should be paid to patients who experience high levels of stress and have low social support. PMID- 22067720 TI - Biologic measures as epidemiological indicators of risk for the development of hypertension in an African American adolescent population. AB - Globally, the health disparity of hypertension is disproportionately greater within the African American population and develops at an earlier age. Elevated and continuous interaction of biologic measures during adolescence may be precursors and indicators of risk for blood pressure changes and the subsequent development of adult essential hypertension. The purpose of this study was to describe (1) the prevalence of biologic measures of risk of hypertension, specifically family history of hypertension, prehypertension, elevated salivary cortisol, and hyperresponsive cortisol and cardiovascular reactivity, and (2) the gender difference in the prevalence of biologic risk factors of hypertension. SUBJECTS AND METHOD: This was an exploratory descriptive design with a nonrandom purposive sample. Participants (N = 106) were high school, African American adolescents, aged 14 to 18 years. Data, including family history of hypertension, resting blood pressure, and blood pressure and cortisol levels before and after induced physiologic stress by cold water hand immersion, were measured. RESULTS: One hundred six African American participants (49 males and 57 females) completed the study. Data described that 71% had a positive family history of hypertension. Overall, the resting blood pressures were 120 mm Hg for systolic and 68 mm Hg for diastolic. Forty-one percent of the patients had prehypertensive blood pressures; 86% had elevated cortisol; 49% had hyperresponsive blood pressure reactivity; and 35% had cortisol hyperresponsivity. Excluding ethnicity, 65% had 3 or more biologic measures of risk of hypertension. Statistically significant gender differences included male systolic pressure and number of males with prehypertension. CONCLUSION: This study provides evidence of the high prevalence of multiple physiologic biologic measures of risk of hypertension factors within a vulnerable population. The continuous interaction of biologic measures over time may increase the susceptibility and risk of essential hypertension development and supports the development of appropriate physiologically based behavioral interventions. PMID- 22067722 TI - A comparison of the effect of glitazones on serum sialic acid in patients with type 2 diabetes. AB - Although management of hyperglycaemia represents one of the principal treatment goals of diabetes therapy, the high incidence of cardiovascular (CV) complications in diabetes also needs effective management. Therefore, the present study was designed to determine and compare the effect of glitazones on serum sialic acid (SSA), a known risk marker for CV disease, along with fasting plasma glucose (FPG), glycohaemoglobin (HbA1-c) and blood lipids, in overweight, previously only diet-treated patients with type 2 diabetes (n=60). The study was conducted for a period of 12 months. Significant improvement in FPG and HbA1-c were shown by both rosiglitazone (p<0.003 and p<0.001, respectively) and pioglitazone (p<0.005 and p<0.001, respectively), compared with baseline, and pioglitazone showed greater beneficial effects on other parameters monitored, significantly reducing total cholesterol (TC) (p<=0.05). Both the drugs showed a decrease in SSA and no significant differences were observed between the groups. However, the decrease was significant only in the pioglitazone-treated group at month 12 (p<=0.05), compared with baseline. A significant decrease in SSA by pioglitazone indicates its greater cardioprotective effect compared with rosiglitazone. PMID- 22067723 TI - Association of diabetes with increased all-cause mortality following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction in the contemporary era. AB - BACKGROUND: We investigated the association between diabetes mellitus (DM) and all-cause mortality in a large cohort of consecutive patients treated with primary percutaneous coronary intervention (PPCI) in the contemporary era. METHODS: We conducted a retrospective analysis of a single-centre registry of patients undergoing PPCI for ST-segment elevation myocardial infarction (STEMI) at a large regional PCI centre between 2005 and 2009. All-cause mortality in relation to patient and procedural characteristics was compared between patients with and without DM. RESULTS: Of 2586 patients undergoing PPCI, 310 (12%) had DM. Patients with DM had a higher prevalence of multi-vessel coronary disease (p<0.001) and prior myocardial infarction (p<0.001). Patients with DM were less commonly admitted directly to the interventional centre (p=0.002). Symptom-to balloon (p<0.001) and door-to-balloon time (p=0.002) were longer in patients with DM. Final infarct-related-artery TIMI-flow grade was lower in patients with DM (p=0.031). All-cause mortality at 30 days (p=0.0025) and 1 year (p<0.0001) was higher in patients with DM. DM was independently associated with increased mortality after multivariate adjustment for potential confounders. CONCLUSIONS: Mortality remains substantially higher in patients with DM following reperfusion for STEMI in comparison with those without diabetes, despite contemporary management with PPCI. Greater co-morbidity, delayed presentation, longer times-to reperfusion, and less optimal reperfusion may contribute to adverse outcomes. PMID- 22067724 TI - The effects of rosiglitazone on myocardial triglyceride content in patients with type 2 diabetes: a randomised, placebo-controlled trial. AB - This was a nested sub-study of a randomised placebo-controlled trial of the effect of 6 months of treatment with rosiglitazone added to existing therapy on myocardial triglyceride (mTG) content in patients with type 2 diabetes (T2D) and prevalent cardiovascular disease (CVD) or at least one additional risk factor. The primary endpoint, mTG content, was measured with cardiac (1)H-magnetic resonance spectroscopy. Of the 99 randomised participants selected for the imaging sub-study, 49 (48%) had complete and interpretable spectroscopy data (age = 58 years, duration of T2D = 9.5 years; 57% women and 69% non-white). There was no significant change in mTG in either group (-0.1 +/- 0.6% and -0.05 +/- 0.8% respectively) and the changes in mTG were not associated with changes in left ventricular structure or function. Compared with placebo, treatment with rosiglitazone for 6 months had no discernible effect on mTG or left ventricular function in this population with long-standing diabetes and CVD. PMID- 22067726 TI - Is genetic screening necessary for determining the possibility of venous thromboembolism in cancer patients? AB - OBJECTIVE: To determine the risk of an association with some genetic polymorphisms involved in venous thromboembolism (VTE) gene variations (FVL, FV H1299R, FII G20210A, MTHFR C677T, MTHFR A1298C, PAI-1 4G/5G, beta-fibrinogen -455 G -> A, FXIII Val34Leu and GpIIIa HPA-1a) in cancer patients. SUBJECTS AND METHODS: Among 78 cancer patients, 28 who had proven first episode of VTE were selected as the patient group, with 50 control samples selected from age-, sex- and body mass index-matched healthy volunteers (healthy group). The differences in frequency of genetic polymorphisms were found to be statistically insignificant between these two groups. RESULTS: Logistic regression analysis after adjustment for age, sex, smoking and hypertension showed no difference. The screened mutations of these genes were not significantly associated with VTE risk. CONCLUSION: There is no possible benefit from genetic screening tests regarding VTE in cancer patients. PMID- 22067725 TI - How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation? AB - We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA PCa-2b) with BBP (up to 0.8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2'-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation. PMID- 22067727 TI - Priorities and realities: addressing the rich-poor gaps in health status and service access in Indonesia. AB - INTRODUCTION: Over the past four decades, the Indonesian health care system has greatly expanded and the health of Indonesian people has improved although the rich-poor gap in health status and service access remains an issue. The government has been trying to address these gaps and intensify efforts to improve the health of the poor following the economic crisis in 1998. METHODS: This paper examines trends and levels in socio-economic inequity of health and identifies critical factors constraining efforts to improve the health of the poor. Quantitative data were taken from the Indonesian Demographic Health Surveys and the National Socio-Economic Surveys, and qualitative data were obtained from interviews with individuals and groups representing relevant stakeholders. RESULTS: The health of the population has improved as indicated by child mortality decline and the increase in community access to health services. However, the continuing prevalence of malnourished children and the persisting socio-economic inequity of health suggest that efforts to improve the health of the poor have not yet been effective. Factors identified at institution and policy levels that have constrained improvements in health care access and outcomes for the poor include: the high cost of electing formal governance leaders; confused leadership roles in the health sector; lack of health inequity indicators; the generally weak capacity in the health care system, especially in planning and budgeting; and the leakage and limited coverage of programs for the poor. CONCLUSIONS: Despite the government's efforts to improve the health of the poor, the rich-poor gap in health status and service access continues. Factors at institutional and policy levels are critical in contributing to the lack of efficiency and effectiveness for health programs that address the poor. PMID- 22067728 TI - Disseminated, eruptive molluscum contagiosum lesions in a psoriasis patient under treatment with methotrexate and cyclosporine. PMID- 22067729 TI - HER3 overexpression as an independent indicator of poor prognosis for patients with curatively resected pancreatic cancer. AB - OBJECTIVE: The association between human epidermal growth factor receptor 3 (HER3) overexpression and survival in patients with curatively resected pancreatic cancer was investigated. METHODS: Tissue samples from 126 pancreatic cancers without hematogenous or peritoneal metastases recovered from macroscopically curative resection were fixed with formalin, embedded in paraffin and subjected to immunohistochemical staining. Semiquantitative scores of zero (no staining or staining in less than 10% of cancer cells), 1+, 2+, or 3+ were assigned to each sample based on the intensity of staining. Scores of 2+ or 3+ were defined as HER3-positive staining, i.e., HER3 overexpression. RESULTS: HER3 overexpression was observed in 52 of the 126 tissue samples (41.3%). There were no associations between HER3 overexpression and clinicopathological factors, including tumor location, tumor size, tumor differentiation, T/N categories according to the International Union against Cancer, and serum carbohydrate antibody 19-9 level (CA19-9). Univariate analysis demonstrated the median survival time of patients with HER3 overexpression was 37.2 months, while that of patients with HER3-negative samples was 58.6 months (p = 0.008). HER3 overexpression, lymph node metastasis, and elevated serum CA19-9 level were independent predictors of poor prognosis based on multivariate survival analysis. CONCLUSION: A new prognostic predictor, HER3 overexpression, was identified for resected pancreatic cancer. PMID- 22067730 TI - Fusion tags: a collection of papers. PMID- 22067732 TI - The role of pain treatment in managing the behavioural and psychological symptoms of dementia (BPSD). PMID- 22067733 TI - A guide to the use and care of vascular access devices in the palliative care setting. AB - There has been a steady increase in the number and range of vascular access devices used in all areas of health care. With this increase there comes a requirement that health professionals dealing with these devices be aware of the range available, indications for use, and the most up to date guidance on the care and maintenance procedures. Care of the device is paramount to preventing complications. This article provides an overview of the types of venous access devices that may be encountered when a patient is transferred to palliative care services, as well as of the procedures for routine maintenance. PMID- 22067734 TI - Development and evaluation of the Pain Assessment in the Communicatively Impaired (PACI) tool: part II. AB - Pain is a common symptom for long-term care residents, particularly those in need of palliative care. However, pain assessment in residents who have communication limitations is challenging. A study was conducted with the aim of developing a pain assessment tool that could feasibly be used by direct care providers in long term care with minimal training yet demonstrating strong psychometric properties. The study used both qualitative and quantitative methods to develop and test the Pain Assessment in the Communicatively Impaired (PACI) tool. Part I of this paper reported on the development phase; this second part reports on the test results. The validity and reliability results of the PACI tool were acceptable, and the convergent validity was moderately strong. A moderate level of interobserver agreement was evident, with kappas ranging from 0.46 to 0.63 for the individual items and a kappa score of 0.59 for the total tool score. The overall results of this study support the psychometric properties and feasibility of the PACI tool, offering preliminary support for its use in clinical practice. PMID- 22067735 TI - The practice of withholding and withdrawing life-support measures among patients with cancer in Jordan. AB - In Jordan, an Arabic Islamic country, decisions around withholding and/or withdrawing life support measures still present both moral and professional dilemmas. The purpose of this study was to explore the use of such measures among patients with cancer in Jordan. The medical records of 436 patients with cancer who were at least 18 years old and who died at a specialized cancer centre in Jordan in 2008 were reviewed retrospectively. Of those, 212 (48.6%) had a written decision to withhold or withdraw life support measures. Among the 436 charts reviewed, only 7 patients (1.6%) had treatment withdrawn, while 212 (48.6%) had treatment withheld. Resuscitation was the most common treatment withheld, followed by medication, and poor prognosis was the most common reason for the decision. The time period between a decision being made and the death of the patient was short, indicating that treatment plans are not being made well in advance. A cultural and religious consensus regarding such decisions is needed to help ensure that a greater proportion of terminally ill people plan their care in advance, and to aid health-care providers in advising their patients and acting in the patients' best interests. PMID- 22067736 TI - Student nurses' experience of their first death in clinical practice. AB - BACKGROUND: It is important to understand how student nurses might feel when confronted with a dying patient, so that appropriate support and education can be offered prior to their placement. This paper aimed to explore student nurses' experiences of their first death in clinical practice to help identify educational, training, and support needs. METHODOLOGY: A qualitative phenomenological approach was adopted and data was collected using a focus group involving five student nurse participants. FINDINGS: The data analysis revealed four themes: the emotional influence of death, skills required, the role of the mentor, and relationships. The students' experiences of their first death in clinical practice caused them considerable anxiety, and they reported feeling inadequately prepared for the reality of the situation. CONCLUSIONS: Educationalists and clinicians alike should give much consideration to finding teaching and learning methods that are appropriate to this challenging subject and that more effectively prepare students for what they might encounter. PMID- 22067737 TI - Discussing life story, forgiveness, heritage, and legacy with patients with life limiting illnesses. AB - AIM: To explore the perceptions that individuals with life-limiting illnesses have about their lives, both positive and negative, and their messages to future generations. METHODS: A preparation and life completion intervention (Outlook) was assessed for acceptability and feasibility in an Australian palliative care setting. This paper reports a qualitative analysis of the participants' responses to the intervention. The intervention sessions were audiotaped, transcribed, and analysed using interpretative phenomenological analysis. RESULTS: Eleven participants were recruited from inpatient and outpatient hospital and hospice settings. Three overarching themes were identified: life review, current situation, and legacy/principles. CONCLUSIONS: The intervention provided insights into individual palliative care patients' sense of self, views of their current situation, hopes, and how they would like to be remembered. PMID- 22067740 TI - Transcriptional regulation of type I interferon gene expression by interferon regulatory factor-3 in Japanese flounder, Paralichthys olivaceus. AB - Type I interferon (IFN) induces the antiviral response in innate immunity. The type I IFN gene cloned from Japanese flounder (Paralichthys olivaceus) has a length of 1189 bp and consisting of 5 exons and 4 introns. In a phylogenetic tree of type I IFNs, Japanese flounder grouped with other Acanthopterygii. To gain insight into the transcriptional regulation of IFN gene, the 1.36 kb 5'-upstream region including numerous canonical motifs to bind transcription factors [for example, IFN regulatory factor (IRF)] was analyzed. In HINAE cells using a luciferase reporter assay, poly I:C-responsive transcriptional activity was found in the region from -634 to -179 bp. This region includes several IRF motifs. In the presence of poly I:C, overexpression of IRF3 and RLR strongly enhanced transcriptional activity. These results suggest that the transcriptional regulation of Japanese flounder type I IFN is regulated by IRF3 after triggering with dsRNA sensors. PMID- 22067741 TI - Yeast-surface expressed BVDV E2 protein induces a Th1/Th2 response in naive T cells. AB - Yeast species such as Saccharomyces cerevisiae are known to be potent activators of the immune system. S. cerevisiae activates the innate immune system by engaging pattern recognition receptors such as toll like receptor 2 (TLR2) and dectin-1. In the current project, we express the immunogenic envelope protein E2 of bovine viral diarrhoea virus (BVDV) on the surface of S. cerevisiae. After successful expression, components of the innate and adaptive immune response induced by the recombinant S. cerevisiaein vitro were analysed to determine if expression in yeast enhances the immunogenicity of the viral protein. Recombinant S. cerevisiae stimulated production of the chemokine CXCL-8 in primary bovine macrophages, but did no stimulate production of reactive oxygen species (ROS) in the same cells. Additionally, bovine macrophages primed with S. cerevisiae expressing viral envelope proteins had a greater capacity for stimulating proliferation of CD4+ T-cells from BVDV-free animals compared to macrophages primed with envelope protein alone or S. cerevisiae without envelope protein expression. Heat inactivation of recombinant S. cerevisiae increased ROS production and capacity to stimulate CD4+ T-cells in macrophages but did not alter CXCL-8 release compared to the live counter-part. Additionally, heat inactivation of recombinant S. cerevisiae induced less INFgamma and IL-4 but equal amounts of IL-10 compared to live yeast T-cell cultures. Our studies demonstrate a use for S. cerevisiae as a vehicle for transporting BVDV vaccine antigen to antigen-presenting cell in order to elicit cell-mediated immunity even in naive animals. PMID- 22067742 TI - Health status, infection and disease in California sea lions (Zalophus californianus) studied using a canine microarray platform and machine-learning approaches. AB - Conservation biologists face many challenges in assessing health, immune status and infectious diseases in protected species. These challenges include unpredictable sample populations, diverse genetic and environmental backgrounds of the animals, as well as the practical, legal and ethical issues involved in experimentation. The use of whole genome scale transcriptomics with animal samples obtained in a minimally invasive manner is an approach that shows promise for health assessment. In this study we assessed the utility of a microarray to identify changes in gene expression predictive of health status by interrogating blood samples from California sea lions (Zalophus californianus) in rehabilitation. A custom microarray was developed from the commercially available dog microarray (Canis familiaris) by selecting probes that demonstrated reliable cross-hybridization with RNA in sea lion blood. This custom microarray was used for the analysis of RNA from 73 sea lion blood samples, from animals with a broad spectrum of health changes. Both traditional classifying techniques and newer artificial neural network approaches correctly classified sea lions with respect to health status, primarily distinguishing between leptospirosis infection and domoic acid exposure. Real time PCR validation for a small set of genes, followed by sequencing, showed good correlation with array results and high identity (96 98%) between the dog and sea lion sequences. This approach to health status classification shows promise for disease identification in a clinical setting, and assessment of health status of wildlife. PMID- 22067743 TI - Myocardial perfusion imaging with (99 m)Tc-tetrofosmin SPECT in breast cancer patients that received postoperative radiotherapy: a case-control study. AB - PURPOSE: To evaluate the cardiac toxicity of radiotherapy (RT) in breast cancer (BC) patients employing myocardial perfusion imaging (MPI) with Tc-99 m Tetrofosmin-single photon emission computer tomography (T-SPECT). MATERIALS AND METHODS: We studied 46 BC female patients (28 patients with left and 18 patients with right BC) treated with postoperative RT compared to a control group of 85 age-matched females. The median time of RT to SPECT was 40 months (6-263). RESULTS: Abnormalities in the summed stress score (SSS) were found in 54% of left BC patients, 44.4% of right BC patients, and 32.9% of controls. In left BC patients there were significantly more SSS abnormalities compared to controls (4.0 +/- 3.5 vs 2.6 +/- 2.0, p = 0.05) and possible trend of increased abnormalities of right BC patients (3.7 +/- 3.0 vs 2.6 +/- 2.0, p = 0.14). Multiple regression analysis showed more abnormalities in the MPI of left BC patients compared to controls (SSS, p = 0.0001); Marginal toxicity was also noted in right BC patients (SSS, p = 0.045). No additional toxicity was found in patients that received adjuvant cardiotoxic chemotherapy. All T-SPECT abnormalities were clinically silent. CONCLUSION: The study suggests that radiation therapy to BC patients result in MPI abnormalities but without apparent clinical consequences. PMID- 22067745 TI - Assessment of the viability of embryos stored in liquid nitrogen produced commercially using culture medium as a complementary test for stereoscopic microscopy. AB - Summary The objective of the present study was to evaluate the viability of frozen embryos obtained from various private farmers in a culture medium for 4 h. Forty-seven embryos were used that had been previously graded as good and fair. These embryos were evaluated using stereoscopic microscopy by experienced clinicians prior to freezing. Embryos were divided in two groups: the non cultured group, made up of six good quality embryos, and five fair; and the cultured group that consisted of 20 good quality embryos and 16 fair. Fifty-four per cent of the good quality embryos achieved a favourable development during culture whereas just 42% of embryos determined to be fair were observed to have adequate development. This evaluation was undertaken by serial photographs obtained at the onset of culture and 4 h later. This finding was corroborated by a more specific technique: terminal deoxynucleotide transferase dUTP nick end labelling-bromodeoxyuridine (TUNEL-BrdU). These results are indicative of the necessity of tight quality controls for commercially produced frozen embryos, as once thawed it is unlikely that clinicians will examine them to determine their physiological status prior to transfer. PMID- 22067744 TI - The interaction between MYB proteins and their target DNA binding sites. AB - Members of the MYB family of transcription factors are found in all eukaryotic lineages, where they function to regulate either fundamental cellular processes, or specific facets of metabolism or cellular differentiation. MYB transcription factors regulate these processes through modulation of transcription at target genes, to which they bind in a sequence-specific manner. Over the past decades, insights have been gained into the molecular interactions between MYB proteins and their cognate DNA targets. This review focuses on those insights, the emergence of common themes in DNA binding by diverse MYB family members. The review also considers gaps in the current knowledge of MYB-DNA interactions, particularly for plant MYB proteins, and how emerging techniques that examine protein-DNA interactions can fill these gaps. PMID- 22067746 TI - GH11 xylanases: Structure/function/properties relationships and applications. AB - For technical, environmental and economical reasons, industrial demands for process-fitted enzymes have evolved drastically in the last decade. Therefore, continuous efforts are made in order to get insights into enzyme structure/function relationships to create improved biocatalysts. Xylanases are hemicellulolytic enzymes, which are responsible for the degradation of the heteroxylans constituting the lignocellulosic plant cell wall. Due to their variety, xylanases have been classified in glycoside hydrolase families GH5, GH8, GH10, GH11, GH30 and GH43 in the CAZy database. In this review, we focus on GH11 family, which is one of the best characterized GH families with bacterial and fungal members considered as true xylanases compared to the other families because of their high substrate specificity. Based on an exhaustive analysis of the sequences and 3D structures available so far, in relation with biochemical properties, we assess biochemical aspects of GH11 xylanases: structure, catalytic machinery, focus on their "thumb" loop of major importance in catalytic efficiency and substrate selectivity, inhibition, stability to pH and temperature. GH11 xylanases have for a long time been used as biotechnological tools in various industrial applications and represent in addition promising candidates for future other uses. PMID- 22067748 TI - Oral contraceptive and progestin-only use correlates to tissue tumor marker expression in women with cervical intraepithelial neoplasia. AB - BACKGROUND: The study was conducted to investigate correlations between combined oral contraceptive (COC), any progestin-only contraceptive, medicated intrauterine device (MID) or systemic progestin-only (Syst-P) use and tumor marker expression in cervical intraepithelial neoplasia compared to nonusers. STUDY DESIGN: One-hundred ninety-five women of fertile age with cervical biopsies ranging histologically from normal epithelium to carcinoma in situ were recruited consecutively. Combined oral contraceptive, Syst-P and MID users were investigated according to the expression of 11 tumor markers. RESULTS: Overexpression of cyclooxygenase-2 (Cox-2) was observed in COC users, while interleukin 10 was underexpressed. When users of progestogen-only contraceptives were analyzed, there was a lower expression of cytokeratin 10 and interleukin 10. When only MID users were analyzed, a high expression of p53 was found. Expression of Cox-2, p53 and retinoblastoma protein differed between COC and MID users. CONCLUSION: The study showed molecular alterations, which, in general, have not been studied previously in COC users and have never been studied in progestogen only users. These biological events might be involved in epidemiological correlations found between hormonal contraceptive use and cervical neoplasms. PMID- 22067747 TI - Secretory phospholipase A2 pathway in various types of lung injury in neonates and infants: a multicentre translational study. AB - BACKGROUND: Secretory phospholipase A2 (sPLA2) is a group of enzymes involved in lung tissue inflammation and surfactant catabolism. sPLA2 plays a role in adults affected by acute lung injury and seems a promising therapeutic target. Preliminary data allow foreseeing the importance of such enzyme in some critical respiratory diseases in neonates and infants, as well. Our study aim is to clarify the role of sPLA2 and its modulators in the pathogenesis and clinical severity of hyaline membrane disease, infection related respiratory failure, meconium aspiration syndrome and acute respiratory distress syndrome. sPLA2 genes will also be sequenced and possible genetic involvement will be analysed. METHODS/DESIGN: Multicentre, international, translational study, including several paediatric and neonatal intensive care units and one coordinating laboratory. Babies affected by the above mentioned conditions will be enrolled: broncho-alveolar lavage fluid, serum and whole blood will be obtained at definite time-points during the disease course. Several clinical, respiratory and outcome data will be recorded. Laboratory researchers who perform the bench part of the study will be blinded to the clinical data. DISCUSSION: This study, thanks to its multicenter design, will clarify the role(s) of sPLA2 and its pathway in these diseases: sPLA2 might be the crossroad between inflammation and surfactant dysfunction. This may represent a crucial target for new anti-inflammatory therapies but also a novel approach to protect surfactant or spare it, improving alveolar stability, lung mechanics and gas exchange. PMID- 22067749 TI - Comment on: Li HW, Wong CY, Yeung WS, Ho PC, Ng EH. Serum anti-Mullerian hormone level is not altered in women using hormonal contraceptives. Contraception 2011;83:582-5. PMID- 22067751 TI - Women's preferences for pain control during first-trimester surgical abortion: a qualitative study. AB - BACKGROUND: To explore women's preferences for pain control during first trimester surgical abortion. STUDY DESIGN: Pre- and postoperative semistructured individual interviews were conducted with 40 women divided into eight strata by anesthesia choice, age and prior vaginal delivery status. We identified key themes in the interviews and analyzed baseline characteristics and responses to close-ended questions within and across the strata. RESULTS: For most women, pain control options were not the primary concern in choosing a clinic for an abortion. Women who received intravenous (IV) sedation had lower pain scores and were more likely to report that they would recommend that method to a friend than women who received local anesthesia alone. Women described the pain as a cramping, tugging, pulling and scraping sensation. Respondents recommended IV sedation for a woman who was very anxious or could not tolerate pain, even though more nausea and vomiting may occur. CONCLUSIONS: Most women felt that pain control decisions should be individualized. PMID- 22067752 TI - Development of a liquid chromatography-tandem mass spectrometry method for measuring plasma and uterine tissue levels of indomethacin in rabbits treated with indomethacin-medicated Cu-IUDs. AB - BACKGROUND: Some side effects of copper intrauterine devices (Cu-IUDs) including increased uterine bleeding, pelvic infections and pain have been reported. The presence of indomethacin in such devices was found to be effective in relieving the symptoms. The aim of this study was to develop and validate a rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for measuring plasma and uterine tissue levels of indomethacin in rabbits after insertion of indomethacin-medicated Cu-IUDs. STUDY DESIGN: Indomethacin was extracted from rabbit plasma and uterine tissue by a simple protein precipitation using acetonitrile. Chromatographic separation was carried out on a Diamonsil C(18) column (150*4.6 mm ID, 5 MUm) with an isocratic mobile phase consisting of methanol, acetonitrile, water and formic acid (45:45:10:0.5, v/v/v/v). Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an atmospheric pressure chemical ionization interface operating in positive ionization mode. Quantitation was performed using selective reaction monitoring mode. The LC-MS/MS method was validated with respect to selectivity, linearity, precision, accuracy, extraction recovery and stability, and then applied to the in vivo studies of indomethacin in rabbits treated with indomethacin-medicated Cu-IUDs. RESULTS: The linear calibration curves of indomethacin in plasma and uterine tissue were obtained over the concentration range of 2.0-400 ng/mL and 4.0-800 ng/mL, respectively. The intra- and interday precision was less than 9.5%, and the relative error was within +/-5.3%. After insertion of indomethacin-medicated Cu-IUDs in rabbits, indomethacin was rapidly absorbed, and peak plasma levels were reached in approximately 1 h. A multiphasic elimination pattern was observed, which was a rapid decline in plasma concentration during the first 100 h followed by a very slow clearance phase. The uterine indomethacin levels were significantly higher than simultaneous plasma levels. CONCLUSIONS: The developed method proved to be rapid and sensitive, and was successfully applied to investigate the absorption and uterine distribution of indomethacin in rabbits after insertion of indomethacin-medicated Cu-IUDs. PMID- 22067753 TI - The copper IUD for emergency contraception, a neglected option. PMID- 22067754 TI - Extended regimens of the contraceptive vaginal ring versus hormonal oral contraceptives: effects on lipid metabolism. AB - BACKGROUND: Combined oral contraceptives used in an extended regimen have been studied because of their potential benefits; however, there have been few publications on extended regimens of contraceptive vaginal rings. The aim of this study was to assess the effects of these two extended regimens on the lipid metabolism of women using these contraceptive methods during 1 year. STUDY DESIGN: This prospective study enrolled 150 women: 75 used a vaginal contraceptive ring (11.7 mg etonogestrel and 2.7 mg ethinyl estradiol), and 75 used oral contraceptives (30 mcg ethinyl estradiol and 150 mg desogestrel). Both groups used their respective method for 84 days followed by a 7-day pause during 1 year. At baseline and every 3 months during the study period, blood was collected to assess total cholesterol, high-density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides and apolipoprotein (apo) A-I and B. The analysis of variance test was used to analyze differences in the results of these exams over time. RESULTS: A total of 62 vaginal ring and 61 oral contraceptive users completed the study. There were no significant differences in the discontinuation rate, mean total cholesterol and fraction levels, apo B concentration or apo A-I/apo B ratio. Vaginal ring users had significantly higher apo A-1 levels than oral contraceptive users. CONCLUSION: Despite the vaginal route of administration, the steroids released by the ring had the same effects on the lipid metabolism and lipoprotein levels typically seen with ethinyl estradiol given either by oral or parenteral routes. PMID- 22067755 TI - Controversies in family planning: management of second-trimester pregnancy terminations complicated by placenta accreta. PMID- 22067756 TI - Assessment of significant factors affecting acceptability of home administration of misoprostol for medical abortion. AB - BACKGROUND: Knowledge on factors affecting acceptability of medical abortion with mifepristone followed by home administration of misoprostol is scarce. The objective of this study was therefore to assess factors affecting acceptability and experience of home use of misoprostol for medical abortion up to 63 days' gestation. STUDY DESIGN: Prospective observational study with acceptability assessed through questionnaires. Factors affecting acceptability were analyzed using multivariate logistic regression. RESULTS: A total of 395 women were included. Independent factors for acceptability were having a partner/friend present and having a positive low-sensitivity urine hCG at follow-up, although most of these patients had successful abortions. Age, gestational length and requirement of extra pain medication did not affect acceptability. CONCLUSION: Home administration of misoprostol is highly acceptable. Increasing the number of complete abortions should be a focus of future research. Women should be encouraged to have a partner/friend present during home administration of misoprostol. PMID- 22067757 TI - Oral contraceptive formulation and risk of breast cancer. AB - BACKGROUND: While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required. STUDY DESIGN: We used data from a multicenter, population-based, case-control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC. RESULTS: Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk. CONCLUSIONS: These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk. PMID- 22067759 TI - Feasibility of postpartum placement of the levonorgestrel intrauterine system more than 6 h after vaginal birth. AB - BACKGROUND: The objective of this study was to determine the feasibility of postpartum levonorgestrel intrauterine system (LNG-IUS) placement on the postpartum ward. STUDY DESIGN: This case-series study took place in a teaching hospital in North Carolina. Women were followed for 6 months, and data on method satisfaction, study design satisfaction and expulsion were collected. Descriptive statistics were used. RESULTS: Forty women enrolled. Twenty-nine women (73%) received the LNG-IUS at a median of 20 h (range 7-48 h) after delivery, and all reported that they would recommend this method of contraception to a friend. Eleven women had a spontaneous expulsion (38%; 95% confidence interval 21, 58). CONCLUSION: Placement of LNG-IUS more than 6 h postpartum was acceptable to women in this study. The expulsion rate of 38% had statistical instability and should be interpreted with caution. However, our report may assist with individual counseling of women interested in postpartum LNG-IUS placement, or in future study designs. PMID- 22067758 TI - A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use. AB - BACKGROUND: Unscheduled bleeding is the main side effect of continuous oral contraceptive pills (OCPs) and has been correlated with the up-regulation of matrix metalloprotineases (MMPs). The study objective was to determine if prophylactic administration of doxycycline (an MMP inhibitor at low subantimicrobial doses) would prevent unscheduled bleeding during the initiation of a continuous OCP. STUDY DESIGN: Subjects using cyclic hormonal contraceptives (combined OCPs, patch or ring) without unscheduled bleeding were switched to continuous OCPs (20 mcg ethinyl estradiol/100 mcg levonorgestrel). They were randomized to receive daily doxycycline [sustained-release subantimicrobial dose (40 mg daily)] or placebo for the first 84 days and then observed for an additional 28 days on the continuous OCP alone. The number of bleeding/spotting days and the time in days it took to achieve amenorrhea were compared using a t test. RESULTS: Sixty-five subjects were randomized. Although the use of doxycycline did not significantly decrease the number of mean bleeding/spotting days in the first 84 days of the study [doxycycline 14.75 (SE 2.30), placebo 17.78 (2.31), p=.36], women who received doxycycline had a significantly earlier onset of amenorrhea [mean last day of bleeding/spotting doxycycline 61.7 (7.7), placebo 85.2 (6.7), p=.03]. CONCLUSION: The coadministration of subantimicrobial dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea. PMID- 22067760 TI - Associations between recent contraceptive use and quality of life among women. AB - BACKGROUND: Whether contraception affects health-related quality of life (HRQoL) is unclear. STUDY DESIGN: We conducted a cross-sectional analysis of routine intake data collected from women aged 18-50 years, including the RAND-36 (Research and Development Corporation) measure of HRQoL, pregnancy intentions and recent contraceptive use. We used multivariable logistic regression to test the relationship between HRQoL and use of any and specific contraceptives. Physical and mental HRQoLs were dichotomized based on US population averages. Models were adjusted for age, race, marital status, education and pregnancy intentions. RESULTS: Among the 726 women, those using any form of contraception were more likely to have average or better mental HRQoL than women using no contraception [adjusted odds ratio (aOR)=1.60, 95% confidence interval (CI) 1.01-2.53]. Women using injectable contraception were less likely than those using combined hormonal methods to have average or better physical HRQoL (aOR=0.26, 95% CI 0.09 0.80) and mental HRQoL (aOR=0.24, 95% CI 0.06-0.86). CONCLUSIONS: Measures of women's HRQoL differ with contraceptive use. PMID- 22067761 TI - The benefits and risks of using a levonorgestrel-releasing intrauterine system for contraception. AB - The contraceptive profile of the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena(r)) is well established, with efficacy similar to that achieved with sterilization and rapid return to fertility after discontinuation of use. The LNG-IUS is typically associated with transient menstrual disturbance during the first few months of use, but this usually settles with continued use, with a concomitant decrease in menstrual blood loss. Overall, the safety profile of the LNG-IUS has been well established across a wide population of women, and the available data do not suggest that the LNG-IUS adversely affects bone health or increase the risk of adverse cardiovascular events or breast and uterine cancers. This article reviews the literature to provide updated information on the risks and benefits associated with the LNG-IUS, particularly focusing on its use in contraception. PMID- 22067762 TI - Immediate versus delayed insertion of the levonorgestrel-releasing intrauterine device following dilation and evacuation: a randomized controlled trial. AB - BACKGROUND: The study was conducted to compare 6-month usage of the levonorgestrel-releasing intrauterine device (LNG-IUD) when placed immediately or 3 to 6 weeks after dilation and evacuation (D&E) procedure. STUDY DESIGN: We enrolled women undergoing D&E at 15 to 23 weeks of gestation. After completion of the D&E, subjects without contraindications to immediate IUD insertion were randomized to immediate or delayed (3 to 6 weeks later) LNG-IUD insertion. Subjects in the immediate group had the LNG-IUD placed using ultrasound guidance. All subjects returned at 3 to 6 weeks and 8 to 10 weeks after D&E and were contacted by phone at 6 months. RESULTS: Of the 93 subjects enrolled, 88 were randomized. All 44 subjects (100%) randomized to immediate insertion had successful IUD placement, while only 20 (45.5%) of the 44 subjects randomized to delayed insertion returned for IUD placement, all of which were successful [difference 54.5%, 95% confidence interval (CI) 39.8%-69.3%]. Seventeen (38.6%) participants in each group were lost to follow-up. Of subjects contacted at the 6 month follow-up phone call, 23 of 27 women (85.2%) and 17 of 27 women (62.9%) were utilizing the LNG-IUD in the immediate and delayed groups, respectively (difference 22.2%, 95% CI -0.4% to 44.8%). Intrauterine device expulsion occurred in three subjects (6.8%) and one subject (5.0%) in whom the IUD was placed in the immediate and delayed groups, respectively (p=1.0). No significant adverse events occurred. CONCLUSION: Significantly more participants had the LNG-IUD placed in the immediate insertion group compared with the delayed insertion group. Given the low risk of complications, immediate post-D&E insertion of the LNG-IUD should be offered, especially for populations that may have difficulty returning for follow-up. PMID- 22067763 TI - Body weight does not impact pregnancy rates during use of a low-dose extended regimen 91-day oral contraceptive. AB - BACKGROUND: This study evaluated the impact of weight on efficacy during use of an extended oral contraceptive (OC). STUDY DESIGN: Data were from a Phase 3 clinical trial evaluating the efficacy of a low-dose 91-day extended regimen of 100 mcg levonorgestrel/20 mcg ethinyl estradiol (LNG/EE; 84 days)+10 mcg EE (7 days) for the prevention of pregnancy. Crude pregnancy rates were calculated for weight and body mass index (BMI) deciles. RESULTS: Of the 1736 women in this analysis, 878 (50.6%) had a BMI greater than 25 kg/m2, and 770 (44.4%) were heavier than 70 kg. Pregnancies occurred in 36 women. Crude pregnancy rates were similar across weight and BMI deciles, with no discernable differences observed between deciles using either classification criterion. CONCLUSIONS: No evidence of any reduction in the level of contraceptive efficacy was observed with this low-dose extended OC regimen in overweight and obese women. PMID- 22067764 TI - Bridge over troubled waters: considerations in transitioning emergency contraceptive users to hormonal methods. AB - BACKGROUND: As emergency contraceptive pills (ECPs) become increasingly available through pharmacies, concerns about potential overuse of this product have emerged. In response, bridging women from ECPs to ongoing contraception was advanced as a solution. STUDY DESIGN: We collected information in Ghanaian pharmacies on ECP users' sexual activity, use of contraceptive methods and reasons for buying ECPs. Further, two behavioral indicators were examined to determine whether a woman should consider using an ongoing contraceptive method: how often she has sex and how she uses ECPs. RESULTS: Of the four types of ECP users, stratified by those two indicators, only women who have sex frequently and use ECPs as their main contraceptive method would be appropriate for, but not necessarily amenable to, bridging. CONCLUSIONS: The challenges of bridging to meet the contraceptive needs of women are discussed in light of the characteristics of emergency contraceptive users and suggest that bridging is not as straightforward as initially conceived. PMID- 22067765 TI - Contraceptive vaginal ring treatment of heavy menstrual bleeding: a randomized controlled trial with norethisterone. AB - BACKGROUND: This study compared the efficacy of the contraceptive vaginal ring (CVR; NuvaRing; N.V. Organon, Oss, the Netherlands) and norethisterone for treatment of idiopathic heavy menstrual bleeding (HMB) during the fertile age. STUDY DESIGN: Ninety-five women with idiopathic HMB were selected in this randomized controlled trial. They were treated with either the CVR (n=48) or norethisterone (n=47) for three cycles. Each cycle consisted of 3 weeks of CVR use and then a 1-week ring-free period or norethisterone tablets, 5 mg three times daily from Cycle Days 5 to 26. Outcome measures were as follows: menstrual blood loss assessed by pictorial blood loss assessment chart (PBAC), duration of menses, hemoglobin, serum ferritin, quality of life (QoL) questionnaire, side effects and overall satisfaction with treatment. RESULT: Significant improvements in PBAC score, the duration of menses, hemoglobin, serum ferritin and QoL were observed at the end of the study in each group. No statistically significant differences were found regarding the mean PBAC score (90.2+/-24.4 vs. 92.3+/ 26.7) and its percent reduction (68.6% vs. 69.5%), duration of menses (5.3+/-1.2 vs. 5.5+/-1.1 days), hemoglobin and serum ferritin at the end of the study between the CVR and the norethisterone groups, respectively. Significantly more ring users were satisfied and elected to continue with treatment. CONCLUSION: Both the CVR and oral norethisterone are effective treatments for idiopathic HMB. The CVR may be an attractive option especially for those requesting contraception as well. PMID- 22067766 TI - Abortion practice in Mexico: a survey of health care providers. AB - BACKGROUND: Little is known about abortion practice in Mexico postlegalization of abortion in Mexico City in 2007. STUDY DESIGN: In 2009, we anonymously surveyed 418 Mexican health care providers at the Colegio Mexicano de Especialistas en Ginecologia y Obstetricia meeting using audio computer-assisted self-interview technology. RESULTS: The majority of respondents were obstetrician gynecologists (376, 90%), Catholic (341, 82%), 35-60 years old (332, 79%) and male (222, 53%) and worked with trainees (307, 74%). Prior to 2007, 11% (46) and 17% (71) provided medical and surgical abortions; now, 15% (62) and 21% (86) provide these services, respectively. Practitioners from Mexico City were more likely to provide services than those from other areas. Most medical abortion providers (50, 81%) used ineffective protocols. Surgical abortion providers mainly used either manual vacuum aspiration (39, 45%) or sharp curettage (27, 32%). Most abortion providers were trained in residency and wanted more training in medical (54, 87%) and surgical (59, 69%) abortion. Among nonproviders, 49% (175) and 27% (89) expressed interest in learning to perform medical and surgical abortion, respectively. CONCLUSION: Given the interest in learning to provide safe abortion services and the prevalent use of ineffective medical abortion regimens and sharp curettage, abortion training in Mexico should be strengthened. PMID- 22067767 TI - Effects of extended regimens of the contraceptive vaginal ring on carbohydrate metabolism. AB - BACKGROUND: There are few publications on the metabolic effects of extended regimens of the contraceptive vaginal ring. The aim of this study was to assess changes in fasting plasma glucose levels and insulin concentration of women using the contraceptive vaginal ring continuously over a 1-year period. STUDY DESIGN: This prospective cohort enrolled 75 women (ages 18-37 years) who used a contraceptive vaginal ring releasing 120 mcg of etonogestrel and 15 mcg of ethinyl estradiol daily continuously for 84 days, followed by a 7-day ring-free interval, during 1 year. Fasting glucose and insulin levels were measured, and homeostatic model assessment was calculated at baseline and every 3 months during the 1-year study period. The repeated-measures analysis of variance test was used to analyze differences in the results of these exams over time. RESULTS: None of the 75 participants had results outside the normal range in any of the assessments. There were no pregnancies during the 1-year period, and a total of 62 participants completed the study. There were no significant changes in mean fasting glucose levels (79.3 and 78.9 mg/dL at baseline and after 12 months, respectively), mean fasting insulin concentration (9.6 and 10.1 MUU/mL) or mean homeostatic model assessment results (1.88% and 1.97%). CONCLUSION: Fasting plasma glucose concentration, insulin levels and homeostatic model assessment values of women using the vaginal ring on an extended regimen did not change significantly over a 1-year period. PMID- 22067768 TI - A life-threatening ectopic pregnancy with etonogestrel implant. AB - BACKGROUND: Etonogestrel contraceptive implant is a highly effective subdermal method of long-acting hormonal contraception for women. CASE: We describe a case of ruptured ectopic pregnancy occurring in a patient with an etonogestrel contraceptive implant (Implanon(r)). The only factor predisposing to a failure in this case is a moderately elevated body mass index of 29. However, the implant was in place for less than 2 years, and the plasma levels of etonogestrel were within the expected range. CONCLUSION: This case report emphasizes the fact that ectopic pregnancy should not be formally ruled out in women using this contraceptive, and it highlights the need for further study of the effect of body weight on this contraceptive method. PMID- 22067770 TI - Contraceptive failure in the United States. PMID- 22067771 TI - No sex for science? Formative research on the acceptability and feasibility of a true contraceptive efficacy clinical trial. AB - BACKGROUND: Recruitment challenges and restrictions on intercourse frequency and timing have stymied previous attempts to implement true contraceptive efficacy clinical trials. STUDY DESIGN: Qualitative research was conducted in Madagascar, South Africa, and the United States to explore the acceptability of three potential true contraceptive efficacy study designs and the feasibility of recruitment for such trials, including characteristics of potential participants who may be willing to join. RESULTS: Participants preferred the study design with the least restrictive sex criteria: participants have sex with assigned contraceptive method/no method on days around ovulation and use condoms on other days. Participants suggested that condom adherence would be low. Differences were noted across sites on whether female participants should be actively seeking pregnancy or not actively seeking pregnancy but willing to accept a pregnancy. Recruitment of participants was expected to be difficult. CONCLUSIONS: Data suggest that a true contraceptive efficacy clinical trial may not be feasible at this time in these settings. PMID- 22067772 TI - Interest in using intrauterine contraception when the option of self-removal is provided. AB - BACKGROUND: The need to ask a clinician to remove an intrauterine contraceptive (IUC) may deter some women from trying the method. There is little risk to a woman who attempts to remove her own IUC. STUDY DESIGN: In 2010, 602 women seeking abortion completed a computerized survey in the waiting rooms of six US abortion clinics. The survey asked women to rate their interest in using the currently available IUCs and a hypothetical "new" self-removable IUC. RESULTS: Overall, 25% of respondents would be more willing to try an IUC if they could remove it themselves. Interest in a self-removable IUC was higher among women who were already considering use of an IUC. After controlling for multiple covariates, women who were likely to have unprotected sex in the future were more willing to consider use of an IUC if they had the option of self-removal (odds ratio 1.63, 95% confidence interval 1.03-2.59). CONCLUSIONS: Informing women that they may safely attempt self-removal of their IUC may increase interest in trying an IUC. PMID- 22067773 TI - IUD use in adolescent mothers: retention, failure and reasons for discontinuation. AB - BACKGROUND: Many professional organizations recommend intrauterine device (IUD) use in adolescents, but data on performance of currently available devices in US teens are scant. We describe IUD continuation, side effect and pregnancy rates in parous adolescents. STUDY DESIGN: Between 2002 and 2008, a cohort of 136 young mothers from an adolescent pregnancy/postpartum program received either a CuT380A or LNG-IUS for contraception. A minimum of 2 years postplacement, IUD status was ascertained by records review and phone interviews. Discontinuation, side effect and pregnancy rates by IUD type were calculated and compared. RESULTS: Mean and median survival times were 25.1 and 14.1 months, respectively, and did not differ by IUD type. Twelve-month continuation was 55%. Of the 87 removals, the most common reasons were expulsion (14.2%), pain (12.2%), bleeding (7.4%), pregnancy desire (6.8%) and pregnancy (4.7%), and rates did not differ significantly by IUD type. First-year pregnancy rates with IUD in situ was 6.2% for the CuT380A and 3.7% for the LNG-IUS (p=.5). Rates of removal for bleeding and pain were similar for both devices. CONCLUSION: Over half of parous adolescents who choose IUDs keep them for at least 1 year. Expulsion rates and pregnancy rates are higher than reported in the general population. PMID- 22067774 TI - Intrauterine lidocaine infusion for pain management during outpatient transcervical tubal sterilization: a randomized controlled trial. AB - BACKGROUND: The study was conducted to examine the effects of a 4% intrauterine lidocaine infusion on patient-perceived pain during transcervical sterilization. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial. Subjects received standard premedication with 800 mg ibuprofen, 2 mg lorazepam, a 10-mL 1% lidocaine paracervical block and transcervical instillation of 5 mL of either 4% lidocaine or saline 3 min prior to insertion of the hysteroscope. Subjects completed a series of 100-mm visual analog scales to measure their perceived pain at set time points during and after the procedure. Serum lidocaine levels were obtained in a subset of subjects. RESULTS: Pain scores at all evaluation points did not significantly differ between groups (lidocaine n=29, saline n=29). Mean lidocaine levels did not differ between groups, and no subject demonstrated symptoms of lidocaine toxicity. The highest serum lidocaine level (4022 ng/mL) occurred 20 min after infusion in a lidocaine-treated subject. CONCLUSION: Intrauterine lidocaine prior to outpatient transcervical sterilization does not decrease pain. PMID- 22067775 TI - Routine training is not enough: structured training in family planning and abortion improves residents' competency scores and intentions to provide abortion after graduation more than ad hoc training. AB - BACKGROUND: Abortion provision remains threatened by the paucity of physicians trained to provide them. Lack of training during residency has been cited by obstetrician and gynecologist (ob-gyn) physicians as a reason for not including abortion in their practice. STUDY DESIGN: We administered surveys on interest, competency and intention to provide abortions to two groups of ob-gyn residents: one experiencing a new comprehensive and structured family planning rotation, and another group at our affiliate hospital's residency program receiving "ad hoc" training during their routine gynecology rotations. Surveys were anonymous and blinded to investigator. RESULTS: The structured family planning rotation group compared to the ad hoc group reported significantly increased competency score using a Likert scale in manual vacuum aspiration (MVA) (4.5 vs. 1; p=.003) and had a higher proportion reporting intent to provide office MVA postresidency (100% vs. 39%; p=.01) and being trained to 22.5 weeks' vs. 12 weeks' gestation (p=.005). In bivariate analysis, competency in MVA was associated with higher intentions to provide MVA after residency (p=.007). CONCLUSIONS: A structured rotation in family planning and abortion for obstetrics/gynecology residents results in increases in competency and intentions to provide abortion, and an association between the two. In-hospital structured training proved to be superior to ad hoc training in our affiliate institution in improving competency and intention to provide abortion after residency. PMID- 22067776 TI - Update on and correction to the cost effectiveness of contraceptives in the United States. PMID- 22067777 TI - Pregnancy outcomes with an IUD in situ: a systematic review. AB - BACKGROUND: While intrauterine devices (IUDs) provide highly effective contraception, pregnancies among IUD users do rarely occur. The objective of this systematic review is to assess the evidence about risks for adverse pregnancy outcomes among women who conceive with an IUD in situ. METHODS: We searched MEDLINE, POPLINE, EMBASE and LILACS databases from inception through April 2011 for peer-reviewed articles containing evidence related to pregnancy outcomes among women who conceived while using copper (Cu) and levonorgestrel-releasing (LNG) IUDs. RESULTS: Nine articles met our inclusion criteria. Women with retained IUDs were at the greatest risk of adverse pregnancy outcomes, including spontaneous abortion, preterm delivery, septic abortion and chorioamnionitis. Cu IUD removal decreased risks but not to the baseline risk of pregnancies without an IUD. One case series examined the LNG-IUD; when left in situ, 8 in 10 ended in spontaneous abortions. CONCLUSION: Pregnancies complicated by a remaining IUD in situ were at greater risk of adverse pregnancy outcomes. Early IUD removal appeared to improve outcomes but did not entirely eliminate risks. PMID- 22067778 TI - Revival of the intrauterine device: increased insertions among US women with employer-sponsored insurance, 2002-2008. AB - BACKGROUND: Use of the intrauterine device (IUD) in the United States has recently increased. New evidence for women with employer-sponsored health insurance permits analysis of variation and trends in such use. STUDY DESIGN: A retrospective analysis of annual IUD insertion rates between 2002 and 2008 was conducted by evaluating claims from the MarketScan(r) Commercial Research Databases for US women insured by plans that covered IUD insertions. Estimates were weighted to be nationally representative. RESULTS: IUD insertion rates increased from 1.6/1000 women of reproductive age to 9.8/1000 over 2002-2008 and varied substantially by state. Insertion rates of the levonorgestrel-releasing intrauterine system (LNG-IUS) increased from 0.4/1000 to 7.7/1000, whereas the insertion rates of copper T380A IUD (copper IUD) increased from 0.6/1000 to 1.5/1000. IUD insertions, which are most common among women aged 25-34 years, increased at roughly the same rate across all age groups. CONCLUSIONS: The sixfold increase in IUD insertion rates between 2002 and 2008 was accompanied by an increase in the share IUD use with the LNG-IUS from 40% to 85%. Substantial geographic and age variations existed. PMID- 22067779 TI - Mifepristone+misoprostol vs. misoprostol alone for early medical abortion. PMID- 22067781 TI - Access to contraception after health care reform in Massachusetts: a mixed methods study investigating benefits and barriers. AB - BACKGROUND: In 2006, Massachusetts passed sweeping health care reform legislation aimed at improving access to health care for residents. This study investigates how this landmark legislation affected contraceptive access for low-income women. STUDY DESIGN: This study included (a) 16 in-depth interviews with family planning providers, (b) 9 focus group discussions with 52 low-income English- and Spanish speaking women, (c) 10 self-administered surveys of family planning administrators and (d) a systematic review of Web sites for government-subsidized insurance plans. RESULTS: Findings from all study components were highly consistent. We found that while most low-income women in Massachusetts continue to regularly obtain contraception, challenges such as maintaining insurance coverage, understanding benefits, securing an appointment with a provider and obtaining prescriptions were identified post reform. Findings about contraceptive affordability under reform were mixed. CONCLUSION: Though health care reform legislation has benefited many women, barriers remain to ensuring consistent access to contraception for low-income women. PMID- 22067782 TI - Does the provision of free intrauterine contraception reduce pregnancy rates among uninsured low-income women? A cohort study: a two North Carolina clinics. AB - BACKGROUND: Low-income women are disproportionately affected by unintended pregnancy. The Access to Resources in Contraceptive Health Foundation was established to provide free levonorgestrel intrauterine contraceptive systems to uninsured women who meet specific socioeconomic eligibility criteria. The aim of this study was to evaluate the effectiveness of this program at reducing pregnancies among uninsured women attending two North Carolina clinics. STUDY DESIGN: This was a retrospective cohort study including uninsured women (aged 15 44 years) who desired contraception, were deemed eligible for the program and attended one of two North Carolina clinics between January 1, 2003, and June 30, 2009. The primary outcome was pregnancy. Pregnancy rates were compared between those women who had a program-approved intrauterine device placed (exposed group) and those women who were eligible for the program, but did not have a device placed (the unexposed group). Questionnaires were used to determine the numbers of pregnancies (and dates of conception), the types of alternative contraception being used and basic demographic information about program participants. The data were analyzed using survival analysis of time to pregnancy. A Cox proportional hazards model was used to estimate a hazard ratio. RESULTS: We attempted to reach 321 patients and obtained 104 responses. After exclusions, data from 90 participants were analyzed. Sixty-five women received a levonorgestrel device, and 25 eligible women did not. Seven pregnancies occurred in the exposed group (11%), all after the IUD was removed; three of these pregnancies were planned. Eight pregnancies occurred in the unexposed group (32%). The median follow-up time was 2.4 years (range: 0.75-4 years) and 1.8 years (0.05-4 years) in the exposed and unexposed groups, respectively. CONCLUSIONS: Provision of a levonorgestrel-releasing device was associated with significantly lower risk of pregnancy than was use of alternative or no contraception. If these data from North Carolina are representative of experience nationwide, then the public health benefit of the Foundation's philanthropy may be large. PMID- 22067783 TI - Mifepristone may shorten the induction-to-abortion time for termination of second trimester pregnancies by ethacridine lactate. AB - BACKGROUND: We reviewed our experience with adding mifepristone to the protocol for the termination of pregnancy up to 24 weeks of gestation by intra-amniotic ethacridine lactate. STUDY DESIGN: The study consisted of women who presented for the termination of a second-trimester pregnancy between August 2000 and July 2008. RESULTS: Of 1245 women who requested a termination of a second-trimester pregnancy, 744 women underwent the induction of abortion by intra-amniotic ethacridine lactate with mifepristone (mifepristone group), and 501 received intra-amniotic ethacridine lactate alone (control group). The proportion of women who delivered within 24 h was 25.94% in the mifepristone group and 10.18% in the control group (p < .001); the failure rate of abortion was 5.38% in the mifepristone group and 4.99% in the control group (p < .001). There was no significant difference in the complication rate between the two groups. The rate of cervical laceration was 0.54% in the mifepristone group and 0.60% in the control group (p = .9315). The rate of retained placental tissue was 6.99% in the mifepristone group and 6.19% in the control group (p = .1112). Nausea was reported by 34.0% of women in the mifepristone group and none in the control group. CONCLUSION: The addition of mifepristone to ethacridine lactate may shorten the induction-to-abortion time compared with the use of ethacridine lactate alone without increasing the number of complications. PMID- 22067784 TI - Effect of shared contraceptive experiences on IUD use at an urban abortion clinic. AB - BACKGROUND: We studied the effect of contraceptive social networking on postabortion intrauterine device (IUD) uptake. This study explores whether women who have heard personal stories of IUD use are more likely to use an IUD for postabortion contraception. STUDY DESIGN: We surveyed 299 women undergoing induced abortion at San Francisco General Hospital's Women's Options Center before and after contraceptive counseling. Both English- and Spanish-speaking women, aged 15 years and older, were surveyed. RESULTS: Fifty percent of women surveyed chose to use an IUD for postabortion contraception. Women choosing IUDs were more likely than women choosing other contraceptives or no contraceptives to be multiparous, Latina and interested in IUDs prior to contraceptive counseling. Disclosure of personal IUD use by a clinic staff member was independently associated with the decision to use an IUD (odds ratio 8.1, 95% confidence interval 3.8-17.2). CONCLUSIONS: Women undergoing abortion in an urban clinic have knowledge and high acceptance of IUDs, and sharing of contraceptive experiences is common among women of all demographics. Controlling for demographics and prior knowledge of IUDs, sharing of personal IUD experiences by providers is significantly associated with IUD use. PMID- 22067785 TI - Analyzing the impacts of abortion clinic structures and processes: a qualitative analysis of women's negative experience of abortion clinics. AB - BACKGROUND: In the United States, the social myth that abortion clinics are unsafe, lonely places is pervasive. Little research has investigated the extent to which women's negative experiences of clinic interactions and processes confirm or contest this myth. STUDY DESIGN: Semistructured interviews with 41 women who received an abortion at a clinic were conducted and analyzed using qualitative analytical techniques in Atlas 5.0. RESULTS: The processes and structures of the abortion clinic necessitated by the realities of antiabortion hostilities lead some women to react negatively to the clinic experience in ways consistent with the social myth of the abortion clinic. Staff interactions can mitigate or alleviate these experiences. CONCLUSIONS: Clinic workers and administrators should be aware that safety structures and processes may create negative experiences for some women. Policymakers should be aware of the extent to which public policies and conflict over abortion render the social myth of the clinic a reality. PMID- 22067786 TI - Can women accurately assess the outcome of medical abortion based on symptoms alone? AB - BACKGROUND: The primary purpose of this study was to evaluate whether women undergoing medical abortion can accurately assess abortion outcome based on symptoms alone. Our secondary aim was to identify predictors of medical abortion failure. STUDY DESIGN: We conducted a case-control study of women undergoing medical abortion from January 1, 2004, to December 31, 2005, who were 63 days' gestation or less and received 200 mg mifepristone followed by 800 mcg of vaginal misoprostol 6-72 h later. Cases were defined as women who required uterine evacuation for a retained gestational sac or ongoing pregnancy. Separate analyses were conducted for the subset of cases with ongoing pregnancies. Controls were defined as women who successfully expelled the pregnancy without uterine evacuation. RESULTS: During the study period, 53 women had a retained gestational sac (N = 26) or ongoing pregnancy (N = 27), and a total of 53 controls were selected, matched by site and date of procedure. Case subjects were more likely than controls to report minimal vaginal bleeding and ongoing pregnancy symptoms and to express doubt that they expelled the pregnancy. When predictive modeling was performed, ongoing pregnancy symptoms, minimal bleeding and gestational age as determined by ultrasound measurement of gestational sac or crown-rump length accurately identified only 68% of medical abortion failures. We also found that the odds of medical abortion failure decreased progressively from approximately 4 to 7 weeks' gestational age, was lowest at approximately 7 weeks and increased from 7 to 9 weeks' gestation. CONCLUSION: Patient symptomatology and self assessment of complete abortion alone are moderately useful in identifying medical abortion failure. An objective measure of complete abortion, such as a pregnancy test, is still required. PMID- 22067787 TI - Impact of etonogestrel-releasing implant and copper intrauterine device on carbohydrate metabolism: a comparative study. AB - BACKGROUND: We investigated the influence of an etonogestrel-releasing (ETG) implant and copper intrauterine device (IUD) on carbohydrate metabolism. STUDY DESIGN: In this nonrandomized, open-label, prospective controlled trial, 40 healthy women received an implant or IUD (20 per group). Outcome measures were fasting glucose, fasting insulin, oral glucose tolerance test (OGTT) and glycosylated hemoglobin A(1)C (HbA(1)C) levels at baseline and after 6 and 12 months. RESULTS: The groups were similar in age, body mass index and laboratory parameters at baseline. Carbohydrate metabolism was not modified by the ETG implant at baseline and at 6 and 12 months (mean +/- SD) (fasting glucose: 85.9 +/- 5.13, 87.05 +/- 5.36, 88.19 +/- 5.05; insulin: 7.77 +/- 2.42, 10.64 +/- 9.4, 8.82 +/- 3.73; OGTT: 94.8 +/- 25.28, 96.5 +/- 19.67, 99.47 +/- 24.6; HbA(1)C: 5.27 +/- .34, 5.55 +/- .39, 5.7 +/- 0.37). The same was true for the IUD (fasting glucose: 88.87 +/- 7.2, 89.65 +/- 5.86, 88.75 +/- 4.79; insulin: 7.94 +/- 3.6, 8.3 +/- 4.1, 7.34 +/- 3.02; OGTT: 96.85 +/- 15.16, 97.48 +/- 13.42, 91.3 +/- 22.16; HbA(1)C: 5.41 +/- .49, 5.75 +/- .41, 5.9 +/- 0.73). CONCLUSIONS: The ETG releasing implant did not affect carbohydrate metabolism in normal women after 12 months. PMID- 22067788 TI - Safety of digoxin for fetal demise before second-trimester abortion by dilation and evacuation. AB - BACKGROUND: Digoxin is used to induce fetal demise before dilation and evacuation (D&E) abortion. Published data on the safety of digoxin in abortion care are limited. STUDY DESIGN: We conducted a retrospective cohort study with historical controls at a large family planning center. We reviewed the records of patients at 18 to 24 weeks' gestation who received digoxin before D&E from May 15, 2007 (date the center initiated digoxin use), through March 31, 2008. We also reviewed the records of patients who presented for D&E without digoxin from February 22, 2006, through May 12, 2007. We compared the rates of immediate complications. RESULTS: We included 566 digoxin patients and 513 controls. Eleven spontaneous abortions occurred in the digoxin cohort; none occurred among controls (p<.001). We found 19 cases of infection in the digoxin cohort and three among controls (odds ratio 5.91; 95% confidence interval 1.74-20.07). Eleven digoxin patients were admitted to a hospital after the preoperative visit; no controls were admitted (p<.001). CONCLUSIONS: Patients who received digoxin before D&E were more likely to experience spontaneous abortion, infection and hospital admission than controls who underwent D&E without digoxin. PMID- 22067789 TI - Bioequivalence study of an oral contraceptive containing ethinylestradiol/drospirenone/levomefolate calcium relative to ethinylestradiol/drospirenone and to levomefolate calcium alone. AB - BACKGROUND: A new tablet formulation containing 0.02 mg ethinylestradiol/3 mg drospirenone/0.451 mg levomefolate calcium (calcium salt containing 0.416 mg L-5 methyltetrahydrofolate) was assessed for bioequivalence compared to the approved oral contraceptive (OC) tablet containing identical amounts of ethinylestradiol and drospirenone and to a tablet containing 0.451 mg levomefolate calcium. STUDY DESIGN: Forty-four subjects received in an intraindividual crossover design single doses of the new tablet formulation or the established ethinylestradiol/drospirenone tablet or the levomefolate calcium tablet. RESULTS: Bioequivalence was demonstrated for ethinylestradiol, drospirenone and L-5 methyltetrahydrofolate (active moiety of levomefolate calcium) between the investigated tablet formulations. The geometric mean ratios of the AUC((0-tlast)) and C(max) values for all three compounds and their 90% confidence intervals were well within the 80%-125% range generally accepted to demonstrate bioequivalence. CONCLUSION: The rate and extent of absorption of ethinylestradiol and drospirenone were not affected by the concomitant administration of levomefolate calcium and vice versa. PMID- 22067790 TI - Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active controlled, parallel-group, US-based multicenter study. AB - BACKGROUND: This study investigated the effects of adding levomefolate calcium 0.451 mg (the calcium salt of L-5-methyltetrahydrofolate; Metafolin(r)) to an oral contraceptive containing ethinylestradiol (EE) 20 mcg/drospirenone (drsp) 3 mg on folate levels in healthy women seeking contraception. STUDY DESIGN: In this randomized, double-blind, multicenter US-based study, women (18-40 years) received 24 weeks (six cycles) of EE/drsp/levomefolate calcium or EE/drsp for 24 days followed by 4 days of levomefolate calcium alone or placebo, respectively. The primary efficacy variables were red blood cell (RBC) and plasma folate levels at 24 weeks. RESULTS: At week 24, increases from baseline in mean RBC (990 +/- 390 nmol/L to 1406 +/- 440 nmol/L) and plasma folate (45.0 +/- 17.6 nmol/L to 60.8 +/- 19.9 nmol/L) levels were observed in women who received EE/drsp/levomefolate calcium [per protocol set (n=262); all values are displayed as mean +/- standard deviation]. In contrast, marginal fluctuations were observed with EE/drsp (p<.0001 for between-treatment differences at week 24). CONCLUSION: Clinically significant increases in folate status were observed with EE/drsp/levomefolate calcium compared with EE/drsp alone in US women of childbearing age. PMID- 22067791 TI - Reduction of the "burst release" of copper ions from copper-based intrauterine devices by organic inhibitors. AB - BACKGROUND: The copper intrauterine device is a contraceptive method that is based on the release of copper ions from a copper wire. Immediately after insertion, the dissolution of copper in the uterine fluid is markedly higher ("burst release") than that necessary for contraception action, leading to a variety of harmful effects. STUDY DESIGN: Pretreatments with organic compounds [thiourea (TU) and purine (PU), 10(-4)-10(-2) M concentration range, 1- and 3-h immersion times] were tested. The dissolution of copper with and without pretreatments in TU and PU solutions was analyzed by conventional electrochemical techniques and surface analysis. RESULTS: Pretreatments in PU solutions reduced the initial corrosion rate of copper in simulated uterine solutions, with inhibitory efficiencies that depend on the PU concentration and on the immersion time assayed. Inhibitory efficiency values higher than 98% for pretreatments with >=10(-3) M PU were found. Conversely, after TU pretreatments, a high copper release was measured. CONCLUSIONS: It was concluded that 10(-3) M PU pretreatment is a promising strategy able to reduce the "burst release" of copper and to ensure contraceptive action. PMID- 22067792 TI - Contraceptive discontinuation and repeat unintended pregnancy within 1 year after an abortion. AB - BACKGROUND: We examined 12-month hormonal contraceptive continuation and pregnancy rates by abortion history. STUDY DESIGN: Women who wanted to avoid pregnancy for at least 1 year were recruited at four San Francisco Bay area family planning clinics on regular service days and on abortion care days. Participants completed baseline and follow-up questionnaires. Multivariable Cox models assessed the factors associated with method discontinuation and pregnancy. RESULTS: Women who were enrolled into the study on the day of their abortion were 20% more likely to discontinue their contraceptive method than women who never had an abortion [adjusted hazard ratio (AHR)=1.21, 95% confidence interval (CI)=1.03-1.42]. Women who had a recent abortion or previous abortion were 60% more likely to have a pregnancy during follow-up than women who never had an abortion (AHR=1.63, 95% CI =1.21-2.20, and AHR=1.66, 95% CI=1.18-2.33, respectively). CONCLUSION: The experience of having an unintended pregnancy and abortion does not lead to behavioral changes that protect against another unintended pregnancy. PMID- 22067795 TI - Old barriers need not apply: opening doors for new contraceptives in the developing world. PMID- 22067793 TI - Continuous oral levonorgestrel/ethinyl estradiol for treating premenstrual dysphoric disorder. AB - BACKGROUND: The study was conducted to investigate continuous daily levonorgestrel 90 mcg/ethinyl estradiol 20 mcg (LNG/EE) on premenstrual dysphoric disorder (PMDD). STUDY DESIGN: In this multicenter, randomized, double-blind, placebo-controlled study, women with PMDD received LNG/EE (n=186) or placebo (n=181) daily for 112 days and completed the Daily Record of Severity of Problems (DRSP). RESULTS: Mean DRSP change from baseline to late luteal phase was significantly greater with LNG/EE than placebo at the late luteal phase of the first estimated cycle (-30.52+/-1.73 [SE] vs. -22.47+/-1.77; p<.001) and the worst 5 days during the last on-therapy estimated cycle (-26.77+/-1.83 vs. 20.89+/-1.82; p=.016). Other primary end points were not statistically significant. Significantly more subject taking LNG/EE (52%) than placebo (40%) responded (>=50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of >=1 improvement) at last on therapy cycle (p=.025). CONCLUSIONS: Continuous daily LNG 90 mcg/EE 20 mcg was well tolerated and may be useful for managing the physical, psychological and behavioral symptoms and loss of work productivity related to PMDD. PMID- 22067796 TI - Preventing repeat abortion in Canada: is the immediate insertion of intrauterine devices postabortion a cost-effective option associated with fewer repeat abortions? AB - BACKGROUND: In 2005, 97,254 abortions were performed in Canada, of which 38% were repeat abortions. The objective of this research was to determine if provision of free intrauterine devices (IUDs) postabortion is associated with a reduction in health-care costs and repeat abortions in a Canadian population compared with provision of oral contraceptives (OCPs) or depo-medroxyprogesterone acetate (DMPA). STUDY DESIGN: A retrospective cohort study was conducted by intention-to treat chart review in a facility providing the majority of abortions in a Canadian health region. All (n=1782) residents of this region who underwent abortion in 2003, 2004 and 2008 were included. One- and 5-year rates of repeat abortion were calculated, and a cost-effectiveness analysis was conducted to compare health-care system costs of providing patients with IUDs, OCPs or DMPA and subsequent repeat abortions. RESULTS: In 2003 and 2004, 1101 index abortions occurred. The main contraceptive cohorts were immediate IUD insertion (n=117, 10.6%), immediate OCP (n=413, 37.5%) and immediate DMPA administration (n=357, 32.4%). After 5 years repeat abortion rates in the respective cohorts were: IUD, 9.4%, OCP, 17.4%, DMPA, 16.2% (p=.05). One-year rates of repeat abortion were not significantly different. Costs of providing contraception and subsequent abortions over 5 years were $142.63 (IUD), $385.61 (OCP) and $384.81 (DMPA) per user. CONCLUSION: The immediate insertion of IUDs postabortion is associated with a lower 5-year rate of repeat abortion than provision of OCPs or DMPA. A cost reduction to the health-care system occurs when providing IUDs postabortion vs. alternate contraception of equivalent duration. PMID- 22067797 TI - Challenging the "insurance theory" of sexual and reproductive health behaviors. PMID- 22067798 TI - Factors influencing partners' involvement in women's contraceptive services. AB - BACKGROUND: Involving women's partners in family planning services may be one avenue by which rates of unplanned pregnancies can be reduced. STUDY DESIGN: In 2009, we surveyed a nationally representative sample of 2113 women aged 18-49 years receiving services from Title X family planning clinics in the United States about their contraceptive use and their current partner, including partners' past involvement in seeking and obtaining contraceptive services. RESULTS: More than half of the women in the sample (56%) indicated that their partners were at least partially involved in their contraceptive services. In the multivariable analysis, race/ethnicity, union status and relationship satisfaction were all significant predictors of partner involvement in contraceptive services. Women reporting that their partners interfere with their birth control were nearly twice as likely as women without interfering partners to report those partners being involved in their contraceptive services. Contraceptive use at last sex was not associated with partner involvement in contraceptive services in either bivariable or multivariable analyses. CONCLUSION: In designing future couple-focused programs, clinics may need to focus on the interpersonal dynamics of couple-based decision-making and behaviors and tailor their programs given the characteristics of clients most likely to avail themselves of these services. PMID- 22067799 TI - Co-prescription of antiepileptic drugs and contraceptives. AB - BACKGROUND: Enzyme-inducing antiepileptic drugs (AEDs) reduce the efficacy of oral contraceptives. Little is known of contraceptive practice among reproductive age women who receive AEDs. STUDY DESIGN: We explored the use of contraceptive methods among Dutch women aged 15 to 49 years with prescriptions of AEDs using pharmacy dispensing database. Drug dispensing data of AEDs and contraceptives in 2006 was retrieved from the InterAction Database (IADB.nl database). The prevalence of contraceptives use and distribution of different contraceptive methods were calculated. RESULTS: Of women who used enzyme-inducing AEDs in combination with any highly effective contraceptive method, over 40% were on an oral contraceptive (OC) containing <50 mcg estrogen. IUDs and injectable contraception were used in 22.5% of women receiving AEDs in combination with any highly effective contraceptive method, and 33.2% in those receiving enzyme inducing AEDs in combination with any highly effective contraceptive method. CONCLUSION: Fertile-age women who received AEDs often relied on less effective contraceptive methods. Prescribers should be more aware of the interaction between AEDs and OCs. PMID- 22067801 TI - Laparoscopic removal of an intra-abdominal intrauterine device: case and systematic review. AB - BACKGROUND: Uterine perforation by intrauterine devices (IUDs) is a rare but well recognized complication. In the past, the presence of adhesions and perforation of viscera often resulted in the need for a laparotomy to remove the IUD. However, advances in laparoscopic technique have allowed surgeons to safely retrieve perforated IUDs. In this review, we analyze uterine perforation by an IUD and assess laparoscopic vs. open methods for removal of a perforated IUD. STUDY DESIGN: A systematic search strategy was applied to several electronic bibliographic databases: Medline/Pubmed, Embase, Cochrane Library, and OCLC PapersFirst. Key words used were IUD, laparoscopy, and uterine perforation. RESULTS: One hundred seventy-nine cases of attempted laparoscopic removal of perforated IUDs were identified in the English literature between 1970 and 2009. Patient age ranged from 17 to 49 years. Diagnostic laparoscopy was performed in all 179 cases reported. Laparoscopic removal of perforated IUDs was achieved successfully in 64.2% (115/179) of cases. CONCLUSION: This systematic review highlights how advances in laparoscopic technique and skill have allowed surgeons to safely retrieve IUDs without laparotomy. We recommend an attempt at laparoscopic removal as first-line treatment in symptomatic patients and as a reasonable treatment option in asymptomatic patients. PMID- 22067800 TI - Deterioration in cardiometabolic risk markers in obese women during depot medroxyprogesterone acetate use. AB - BACKGROUND: Highly effective contraception is essential in obese women, but it should not increase their risk of developing or worsening obesity-related cardiometabolic illness. The purpose of this 18-week prospective experimental study was to compare the impact of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on cardiometabolic markers in obese and normal-weight women. METHODS: Normal-weight [body mass index (BMI) 18.5-24.9 kg/m(2)] and obese (BMI>=30 kg/m(2)) women received injections of 104 mg DMPA-SC at baseline and 12 weeks later. Markers of cardiometabolic risk measured at baseline and 18 weeks after the first injection included body morphometry, fasting blood tests, and oral and frequently sampled intravenous glucose tolerance tests (FSIGT). RESULTS: At baseline, median gravidity, BMI, abdominal circumference, and acute insulin response to intravenous glucose were higher and high-density lipoprotein (HDL) cholesterol and insulin sensitivity (S(I) from FSIGTs) were lower in the 10 obese participants than the five normal-weight women (p<=.05 for each). While there was no significant difference between median baseline and follow-up values among normal-weight women, the difference between median baseline and follow-up among the obese cohort was significantly higher for BMI and lower for HDL cholesterol and insulin sensitivity (S(I)) (p<=.05 for each). The absolute changes for routinely measured clinical laboratory values of metabolic decline were no different among the normal-weight vs. obese women. The difference in absolute change in beta-cell compensation for insulin resistance [disposition index (DI)] was significant between the two groups at follow-up, with the normal-weight group experiencing an increase in DI while the obese group experienced a decline in DI (188.5 vs. -286, p=.04). CONCLUSIONS: Obese women have an increased baseline cardiometabolic risk when compared with normal-weight women at baseline. There was a significantly greater decline in beta-cell compensation for insulin resistance in obese women on DMPA. Our data suggest potential deleterious effects of DMPA on glucose regulation in obese women. Further studies should elucidate the long-term cardiometabolic consequences of DMPA use in obese women. PMID- 22067802 TI - Contraceptive efficacy and safety of HerbOshieldTM vaginal gel in rats. AB - BACKGROUND: Spermicides represent one of the methods of contraception. The synthetic agents available as spermicides produce severe side effects. Hence, there is a need to replace these agents with safe and effective agents such as plant-based contraceptive agents. STUDY DESIGN: The objective of the present study was to develop and evaluate a stable, safe, effective and easily acceptable contraceptive delivery system containing herbal drug. Efforts were made to evaluate the contraceptive potential of the hydroalcoholic extract from the seeds of Annona squamosa Linn. and the vaginal gel HerbOshieldTM containing the extract. RESULTS: Spermicidal effect was evaluated in vitro using healthy human spermatozoa and in vivo in rats. The in vitro results demonstrated that HerbOshieldTM vaginal gel is an effective spermicide. At a 100-mg/mL dose, complete immobilization of human spermatozoa was observed within 20 s. None of the treated animals conceived, indicating 100% contraceptive effect as compared to Gynol II, a nonoxynol-9-containing marketed formulation, which showed only 67% contraceptive effect in vivo. HerbOshieldTM vaginal gel was found to be safe in animals during a 14-day toxicity study. CONCLUSIONS: HerbOshieldTM vaginal gel was found to be safe and effective in rats and could be developed as a potential vaginal contraceptive for future use in humans. PMID- 22067803 TI - Characteristics of women who undergo second-trimester abortion in the setting of a fetal anomaly. AB - BACKGROUND: Most women diagnosed with a fetal anomaly terminate the pregnancy. Little is known about utilization of two procedures: dilation and evacuation (D&E) and induction termination. STUDY DESIGN: This retrospective cohort study included all women seen at the University of California, San Francisco (UCSF) Prenatal Diagnosis Center (PDC) who underwent a second-trimester abortion for an anomalous pregnancy from 2005 to 2008. We abstracted variables from the PDC database and medical charts to identify predictors associated with undergoing D&E. RESULTS: Three quarters of the 192 women underwent D&E (n=148). Higher maternal age, proximity to UCSF, earlier gestational age, singleton gestation and genetic anomaly were associated with undergoing D&E. In adjusted analysis, earlier gestational age and singleton gestation were associated with undergoing D&E. CONCLUSIONS: The D&E procedure was more commonly utilized for terminating an anomalous pregnancy at UCSF than medical induction. Further inquiry is needed to explore how provider counseling influences the choice of D&E vs. induction. PMID- 22067804 TI - A pilot study of women's knowledge of pregnancy health risks: implications for contraception. AB - BACKGROUND: This study was performed to assess women's knowledge of the health risks of pregnancy and how their assessment of pregnancy risks compared to their estimates of the risks of oral contraceptives. STUDY DESIGN: A survey, which asked both open-ended and specific questions about the health benefits and risks of pregnancy, was administered verbally on a one-on-one basis to nonpregnant, English-speaking, reproductive-age women. RESULTS: Of the 248 women who provided information for analysis, over one quarter of women could not correctly name any health risk associated with pregnancy. When shown a list of potential health risks, only 13.3% correctly identified all the health problems that increased in pregnancy. Only 49% knew that risks of venous thromboembolism (VTE), diabetes and hypertension increase in pregnancy; 30.6% did not know that VTE risk increases. Over 75% of respondents rated birth control pills as more hazardous to a woman's health than pregnancy. The greater the women's education, the more likely she was to believe that oral contraceptives are riskier than pregnancy. CONCLUSION: This pilot project clearly demonstrates a need to assess women's understanding of the health hazards of pregnancy on a national level. Underestimation of pregnancy risks can lead to contraceptive method discontinuation, can decrease motivation to seek preconceptional care and can lead to greater medicolegal liability for providers of obstetrical care. PMID- 22067805 TI - Extended intervention time and evaluation of sperm suppression by dienogest plus testosterone undecanoate in male rat. AB - BACKGROUND: The potential of using dienogest [DNG, 40 mg/kg body weight (bw)] plus testosterone undecanoate (TU, 25 mg/kg bw) in rats for development of a once a-month male hormonal contraceptive has been reported earlier in our laboratories. STUDY DESIGN: In the present study, we report a separate efficacy evaluation of the same combination, DNG (40 mg/kg bw) and TU (25 mg/kg bw) in which interval of drug administration has been extended further to 45 and 60 days instead of every 30 days. RESULTS: Complete sperm suppression was observed in rats sacrificed either 60 or 90 days after DNG+TU administration, for two injections at 45-day interval. The neutral alpha-glucosidase activity in these treated rats remained in the normal range. Germ cell loss due to apoptosis was frequently observed both after 60 or 90 days of combination treatment. Significant decline in serum gonadotropin and testosterone, both serum and intratesticular levels, were observed in the treated rats. Following stoppage of treatment (given at 45-day interval) after two (0 and 45 days) or three injections (0, 45 and 90 days), complete restoration of spermatogenesis was observed by 120 and 165 days, respectively. The sperm suppression, however, could not be sustained when the period of combined drug administration was extended from every 45 to 60 days. CONCLUSIONS: Dienogest plus testosterone undecanoate in the above doses retained contraceptive effectiveness when administered every 45 days but not 60 days. The spermatogenic arrest was completely reversible once drug treatment is stopped. The dose and the frequency of intervention can be extrapolated in future clinical trials. PMID- 22067806 TI - Knowledge and beliefs about mechanism of action of birth control methods among European women. AB - BACKGROUND: Adequate knowledge is essential for making informed decisions. We attempted to determine the level of knowledge about mechanisms of action of birth control methods in five representative samples of European women. STUDY DESIGN: Randomly selected women, aged 18-49 years, completed an anonymous survey in Germany, France, the UK, Sweden and Romania (N=1137). Participants were asked about how contraceptive methods work and if providers should inform them about this issue. Multiple linear regression was used to evaluate women's characteristics associated with their knowledge of mechanisms of action. RESULTS: The majority of women identified the unequivocal mode of action of condoms, sterilization and abortion. Fewer than 2% identified all possible mechanisms of action of hormonal contraceptives and intrauterine devices. Highly educated women correctly identified the mechanism or mechanisms of action of more methods than less educated women (beta=0.22, 95% confidence interval 0.01-0.43). Regardless of their sociodemographic characteristics and their belief about when human life begins, most women (75%) stated that the provider should inform them about possible postfertilization effects. CONCLUSIONS: European women have low knowledge about mechanisms of action of several contraceptive methods. The majority want to be informed about possible postfertilization effects. Since adequate knowledge is essential for making informed decisions, providers are encouraged to inform women about all possible mechanisms of action of contraceptives. PMID- 22067807 TI - Prevalence of genital tract infection with Entamoeba gingivalis among copper T 380A intrauterine device users in Egypt. AB - BACKGROUND: This study was performed to study the prevalence and potential pathogenicity of E. gingivalis in the genital tracts of intrauterine contraceptive device (IUD) users. STUDY DESIGN: A prospective study conducted at the Obstetrics and Gynecology Department and Fertility Care Unit, Mansoura University Hospital, Egypt. The study was carried out on 87 IUD users and 87 nonusers. The copper T 380A IUD was removed from each woman and washed with phosphate-buffered saline (PBS) pH 7.4; the IUD wash was centrifuged. The sediment was resuspended in 2 ml PBS and divided into two portions. One portion was used for preparation of direct and iron hematoxylin-stained smears. Direct smears and stained smears were examined for detailed morphology. The second portion of the sediment was used for DNA extraction and subsequent PCR amplification targeting the small subunit ribosomal RNA of E. gingivalis. RESULTS: The parasite was found in 12.64% of IUD users and in 6.9% of non users (p>.3). It was found that 90.9% of those harboring E. gingivalis in their genital tract had the parasite in their oral cavity. The percentage of genital infection in IUD users increased with low level of education, rural areas, insertion in primary health-care center and among those not washing hands before checking the strings. In the infected cases, vaginal discharge was more common (81.8%) than in noninfected cases (32.9%), such difference was statistically significant (p<.05). Also, excessive vaginal discharge is more common than backache and menorrhagia in the infected cases. CONCLUSION: Higher incidence of E. gingivalis infection in IUD users is related to oral cavity infection, residence, the facility where they inserted their IUD and washing hands attitude before checking the strings. We recommend treatment of gingival infection, proper counseling and medical education on oral and genital tract hygiene for IUD users. PMID- 22067808 TI - A qualitative exploration of emergency contraception users' willingness to select the copper IUD. AB - BACKGROUND: The copper T intrauterine device (IUD) is an effective but underutilized method of emergency contraception (EC). This study investigates the factors influencing a woman's decision around which method of EC to select. STUDY DESIGN: In-depth interviews with 14 IUD and 14 oral EC users aged 18-30 years accessing public health clinics. RESULTS: Emergency contraception users associated long-term methods of contraception with long-term sexual relationships. Women were not aware of the possibility of using the copper IUD for EC. Cost was identified as a major barrier to accessing IUDs. Perceived side effects and impact on future pregnancies further influenced the EC method a participant selected. CONCLUSIONS: Women think about contraception in the context of each separate relationship and not as a long-term individual plan. Most women were unaware of the copper IUD for EC. Furthermore, there is little discussion between women and their health-care providers around EC. PMID- 22067809 TI - Couples' acceptability of the SILCS diaphragm for microbicide delivery. AB - BACKGROUND: Disposable plastic applicators used in microbicide gel studies are expensive and have a negative environmental impact. The SILCS diaphragm is a barrier contraceptive that could offer a reusable delivery system. STUDY DESIGN: Thirty-six couples in this randomized, cross-over study evaluated single- and double-sided gel delivery from a SILCS diaphragm compared with gel from an applicator. Couples used each gel scenario during two acts of intercourse and completed acceptability questionnaires after each. RESULTS: All three scenarios received favorable ratings for ease of application, acceptability and perceived effectiveness. Both female and male participants tended to rate the gel applicator significantly more favorably than either SILCS gel delivery scenarios for all attributes except messiness/leakage and effectiveness. Additionally, about 60% of female participants and about half of male participants preferred the gel applicator to either of the gel delivery systems using SILCS. The preference for the SILCS scenario for pregnancy protection was statistically significant for both sexes. Male participants were also significantly more likely to prefer the SILCS single-sided delivery system to the gel applicator for protection from sexually transmitted infection. CONCLUSIONS: In this study population, participants found the gel applicator to be more acceptable than either single- or double-sided gel delivery from a SILCS diaphragm. Further research of the SILCS as a microbicide delivery system should be implemented to assess its acceptability among study populations that reflect diverse potential user groups such as women and men from both low and high HIV prevalence settings including HIV-positive populations and with and without experience using female barrier methods. PMID- 22067810 TI - Feticidal digoxin injection before dilation and evacuation abortion: evidence and ethics. PMID- 22067811 TI - Infection and extramural delivery with use of digoxin as a feticidal agent. AB - BACKGROUND: Many abortion providers use digoxin to induce fetal demise prior to dilation and evacuation (D&E). Our primary objective was to examine the frequency of infection and extramural delivery following digoxin use. STUDY DESIGN: We conducted a retrospective single-cohort study. Inclusion criteria were all women between 18 and 24 weeks of estimated gestational age who received digoxin in preparation for D&E at our outpatient facility. We queried two electronic databases to collect data on the frequency of extramural delivery and the rate of perioperative infection. RESULTS: From January 1, 2000, to December 31, 2008, 4906 abortions were performed between 18 and 24 weeks of estimated gestation with digoxin injection administered as feticidal agent 1 day prior to D&E. Extramural delivery frequency was 0.30%, and infection frequency was 0.04%. There were no significant differences in the frequency of extramural deliveries across procedure year (p = .2), estimated gestational age (p = .3), race/ethnicity (p = .2) or maternal age (p = .3). CONCLUSION: Rates of extramural delivery and infection are acceptably low following digoxin use prior to scheduled D&E. PMID- 22067812 TI - Imaging of vascular smooth muscle cells with soft X-ray spectromicroscopy. AB - Using X-ray microscopy and spectromicroscopy, vascular smooth muscle cells (VSMCs) were imaged, prepared without using additional embedding material or staining, but by applying simple, noncryo fixation techniques. The cells were imaged with a compact source transmission X-ray microscope and a scanning transmission X-ray microscope (STXM). With the STXM, spectromicroscopy was performed at the C K-edge and the Ca L(III,II)-edges. VSMCs were chosen because of their high amount of actin stress fibers, so that the actin cytoskeleton should be visible. Other parts of the cell, such as the nucleus and organelles, were also identified from the micrographs. Both in the spectra and the images, the effects of the different preparation procedures were observable. Furthermore, Ca hotspots were detected and their density is determined. PMID- 22067813 TI - Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients. AB - OBJECTIVE: To evaluate the incidence and risk factors associated with venous thromboembolism (VTE) in children admitted to pediatric intensive care units (PICUs). DESIGN: Prospective observational study. SETTING: Eleven tertiary care PICUs in the United States. PATIENTS: Children who were admitted to PICUs and had radiographically confirmed VTE over a rolling 6-month period were enrolled in the study. Demographic, patient-related, and outcomes data were collected and compared with all children admitted during the same period. INTERVENTIONS: None. RESULTS: : Sixty-six symptomatic VTE were documented in sixty-two patients among 6653 patients admitted to 11 PICUs. Thirteen (19.7%) of the thrombi were present on admission. The incidence rate was 0.74% (range, 0-2.7% per PICU) with a point prevalence of 0.93%. Doppler ultrasound was most frequently used to diagnose or confirm a suspected VTE. Variables associated with unadjusted risk for VTE include: younger age (3.8 months for patients with VTE vs. 51 months for non-VTE patients, p < .001), cardiac diagnosis (41% in VTE cases vs. 15% in non-VTE, p < .001), pre-/post-operative status (63% in VTE cases vs. 40% in non-VTE, p = .001), presence of central venous catheter (88% in VTE case vs. 17% in non-VTE, p < .001), or mechanical ventilation (85% in VTE cases vs. 30% non-VTE, p < .001). Multivariate analysis showed increased risk of VTE with CVC (odds ratio 6.9; confidence interval 2.7-17.5) and mechanical ventilation (odds ratio 2.8; confidence interval 0.98-7.93). Children with VTE were sicker (Pediatric Index of Mortality 2 score risk of mortality of 3.0% vs. 0.9%; p<0.0001), stayed longer in the ICU (21.2 days vs. 1.6 days; p < .0001) and had increased mortality (10.2% vs. 2.6; p < .0001). CONCLUSIONS: Children admitted to the PICU have an increased risk of VTE. The presence of a CVC is the strongest risk factor for VTE in this PICU population. Children with VTE were younger, sicker, stayed longer in PICU, and had a higher mortality rate. PMID- 22067814 TI - The autopsy: underutilized weapon in the pediatric intensive care unit. PMID- 22067815 TI - Follow-up after a child's death in the pediatric intensive care unit: Can it improve family outcomes? PMID- 22067816 TI - Venous thromboembolism in the pediatric intensive care unit: increased incidence or increased awareness? PMID- 22067817 TI - Oncology patients in the pediatric intensive care unit: it's time for prospective study. PMID- 22067818 TI - The pediatric BUS has arrived: is bedside ultrasound in the pediatric intensive care unit a feasible option? PMID- 22067819 TI - Pediatric heart transplant graft ischemic time and early morbidity. PMID- 22067820 TI - Parental inclusion in pediatric intensive care rounds: how does it fit with patient- and family-centered care? PMID- 22067821 TI - Family conferences in the pediatric intensive care unit: how meaningful and memorable? PMID- 22067822 TI - Cerebral edema in diabetic ketoacidosis: time to go with the (cerebral blood) flow? PMID- 22067823 TI - Intracranial pressure monitoring in meningitis: thinking beyond traumatic brain injury. PMID- 22067824 TI - Toward individualized treatment of acute respiratory distress syndrome: response guided mechanical ventilation. PMID- 22067825 TI - Extracorporeal membrane oxygenation in the 21st century: a decade of change. PMID- 22067826 TI - Review of dengue hemorrhagic fever and shock syndromes - comments. PMID- 22067827 TI - Invasive versus noninvasive intracranial pressure monitoring in children with acute liver failure. PMID- 22067829 TI - Novel H1N1 influenza in pediatric intensive care units: what to be concerned about. PMID- 22067830 TI - Quantitative analysis of the ion-dependent folding stability of DNA triplexes. AB - A DNA triplex is formed through binding of a third strand to the major groove of a duplex. Due to the high charge density of a DNA triplex, metal ions are critical for its stability. We recently developed the tightly bound ion (TBI) model for ion-nucleic acids interactions. The model accounts for the potential correlation and fluctuations of the ion distribution. We now apply the TBI model to analyze the ion dependence of the thermodynamic stability for DNA triplexes. We focus on two experimentally studied systems: a 24-base DNA triplex and a pair of interacting 14-base triplexes. Our theoretical calculations for the number of bound ions indicate that the TBI model provides improved predictions for the number of bound ions than the classical Poisson-Boltzmann (PB) equation. The improvement is more significant for a triplex, which has a higher charge density than a duplex. This is possibly due to the higher ion concentration around the triplex and hence a stronger ion correlation effect for a triplex. In addition, our analysis for the free energy landscape for a pair of 14-mer triplexes immersed in an ionic solution shows that divalent ions could induce an attractive force between the triplexes. Furthermore, we investigate how the protonated cytosines in the triplexes affect the stability of the triplex helices. PMID- 22067832 TI - Attenuated Bordetella pertussis BPZE1 as a live vehicle for heterologous vaccine antigens delivery through the nasal route. AB - Whereas the great majority of the current vaccines are delivered through the parenteral route, mucosal administration has been increasingly considered for controlling infection and preventing disease. Mucosal vaccination can trigger both humoral and cell-mediated protection, not only at the targeted mucosal surface, but also systemically. In this regard, nasal vaccination has shown great potential. The live attenuated strain of Bordetella pertussis, BPZE1, is particularly attractive and promising as a nasal vaccine delivery vector of heterologous antigen vaccine candidates. BPZE1 was originally developed as a live nasal pertussis vaccine candidate, and is currently undergoing phase I clinical trial in human (http://www.child-innovac.org). Highly adapted to the human respiratory tract and offering several potential protein carriers for presentation of the heterologous antigen vaccine candidates, BPZE1 represents an appealing platform for the development of live recombinant vaccines delivered via the nasal route that would confer simultaneous protection against pertussis and the targeted infectious disease(s). PMID- 22067833 TI - Unemployment figures at highest level: a health warning. AB - The effects of unemployment can have a detrimental impact on individuals, families and society. It has been announced that the latest unemployment figures demonstrate that the employment rate fell by 0.3 percentage points to 70.4% of the working population in the 3months to August. This reflects the fragility of the global economy and the Government's aspirations to reduce spending. PMID- 22067831 TI - The genetic toolbox for Leishmania parasites. AB - Leishmania parasites cause a variety of devastating diseases in tropical areas around the world. Due to the lack of vaccines and limited availability of drugs, new therapeutic targets are urgently needed. A variety of genetic tools have been developed to investigate the complex biology of this parasite and its interactions with the host. One of the main techniques is the generation of knock out parasites via targeted gene replacement, a process that takes advantage of the parasites ability to undergo homologous recombination. Studying the effect of gene deletions in vitro and in infectivity models in vivo allows understanding the function of a target gene and its potential as a therapeutic target. Other genetic manipulations available include episomal and chromosomal complementation and the generation of overproducer strains. However, there are also limitations, such as the lack of RNA interference machinery in most Leishmania species and limited options for inducible expression systems. The genomes of several Leishmania species have now been sequenced and will provide powerful resources in combination with the genetic tools that are available. The increasing knowledge of parasite biology and host parasite interactions derived from these studies will raise the number of potential therapeutic targets, which are sorely needed to combat leishmaniasis. PMID- 22067834 TI - Promoting better care for patients with dementia. AB - Admission to hospital or a visit to a local clinic can be a frightening experience for a patient with dementia who faces interactions with strangers in unfamiliar surroundings. A nursing team on an acute medical ward for individuals with respiratory conditions, or in a busy general practice, simply has little time to assess what the patient wants to communicate and provide reassurance. PMID- 22067835 TI - Nutrition: safe practice in adult enteral tube feeding. AB - The use of enteral feeding tubes, such as nasogastric and gastrostomy tubes, to support a patient's nutritional intake is generally considered to be safe and effective. However, recent alerts and recommendations from the National Patient Safety Agency (NPSA) regarding enteral feeding have led health professionals to review their practice and guidelines. This article explores safe practice in enteral tube feeding in the light of three NPSA alerts: Promoting safer measurement and administration of liquid medicines via oral and other enteral routes (2007), Early detection of complications after gastrostomy (2010) and Reducing the harm caused by misplaced nasogastric tubes in adults and children (2011). PMID- 22067836 TI - Rheumatoid arthritis: treating to target with disease-modifying drugs. AB - Treating to target is an established concept in a number of long-term conditions, which aims to improve outcomes and prevent disease progression. Treatment targets in rheumatoid arthritis (RA) are to control the signs and symptoms of significant inflammatory disease activity, with the ultimate goal of remission from disease. Assessment of patients' disease activity includes clinical examination of the number of swollen and tender joints, combined with measurement of inflammatory markers and visual analogue scales of patients' overall wellbeing and symptoms. Early initiation and rapid dose escalation of disease-modifying anti-rheumatic drugs (DMARDs) has been shown to be crucial to optimizing disease control, protecting joints from destruction and preserving health-related quality of life. Corticosteroids can be prescribed for oral use but are often given by intra muscular or joint injection in times of flare to minimize the risks of side effects. The rational use of non-steroidal anti-inflammatory drugs and analgesia remains important to symptom management throughout the patient journey. In part two of this three-part series, the concept of treating to target in rheumatoid arthritis is outlined, including the role of the nurse in optimizing outcomes and an overview of treatment options using conventional DMARDs. Part three will cover the use of biologic agents, which have increased treatment options for RA, but their use is reserved for patients with severe disease activity who have failed to respond to adequate trials of DMARDs. PMID- 22067837 TI - Using Actico bandaging for chronic oedema/lymphoedema management. AB - Actico has been used successfully within clinical and community settings and is best used as part of a multi-layered lymphoedema bandaging (MLLB) system. This system is designed to produce a semi-rigid casing that is comfortable enough to allow patients to continue with their activities and exercises so as to generate an optimal resisted muscle pump action within. Correct application is key to using this cohesive short-stretch bandage, and collaborative working between clinics and community nurses is made easier through using Actico as part of oedema management. The case studies enclosed aim to illustrate the use of Actico MLLB for both patients and clinicians. PMID- 22067838 TI - Implementation of 'sign-off' mentorship: different perspectives. AB - Students who entered nurse training from September 2007 onwards are required to have a sign-off mentor (SOM) in their final clinical placement. The sign-off mentor is responsible for confirming to the Nursing and Midwifery Council (NMC) that a student nurse has met all the requirements of pre-registration clinical assessment and can be registered as a nurse. This became mandatory in September 2010, and this article describes how one acute NHS foundation Trust implemented and managed this process, with contributions from practice education facilitators, an SOM and a student. PMID- 22067839 TI - Serving within the British Army: research into mental health benefits. AB - The mental health (MH) of soldiers remains extremely newsworthy and is regularly featured in high profile media forums that focus on post-traumatic stress disorder. However, the authors feel that there are distinct benefits to serving within the Army, and that it provides effective occupational medical, MH and welfare support. This research study explores potential benefits and stressors of being in the Army and provides an overview of Army mental health services (AMHS) through the perspectives of AMHS personnel, 84% of which were nurses. The study indicated that the Army can provide a protective community, sharing a bond based on common values and experiences. The Army can provide soldiers with career opportunities that are not available in civilian life, and there are opportunities to develop an employment profile, enhanced by internal and external educational training, and encapsulated within a progressive career pathway. The Army can also be seen to offer an escape route, preventing soldiers entering a life of crime, and supplying the stable family these soldiers had never experienced. The provision of leadership, within an environment where soldiers are valued and stigma is not tolerated can potentially shield against MH problems. PMID- 22067840 TI - Seasonal influenza: what every nurse needs to know. AB - Professor Alan Glasper discusses this year's seasonal influenza advice from the Department of Health in preparation for winter, and the increasing importance of influenza vaccination by nurses, for nurses. PMID- 22067841 TI - A new paradigm in patient safety. AB - John Tingle, Linda Gibson and Maria Ferrante discuss a new framework for the patient safety agenda. PMID- 22067842 TI - Supporting the self and others: from staff nurse to nurse consultant. Part 11: a strategic model. AB - The previous articles in this series have focused primarily on support and supervision at a ward or unit level, and have examined the practicalities of mentorship, clinical supervision, giving feedback, dealing with conflict and a number of other strategies. This practical application is relevant to the staff nurse, team leader and nurse consultant. At a more strategic level (those of the hospital, Trust or national level), we need to step back from the interactional and face-to-face structures and examine the organization of support and supervision strategically. PMID- 22067843 TI - Exploring the implications of modernized European legislation. AB - On many occasions in this column, I have discussed the unique experience of the student nurse and the many ways that that experience differs from other students within the university. In June, the European Commission published a consultation on a green paper entitled Modernising the Professional Qualifications Directive, the aim of which was to modernize the legislation allowing individual EU citizens to realize their individual right to work anywhere in the EU. This embraces nurses as one of many professional groups; however, there are a number of issues which must be considered discretely. PMID- 22067844 TI - Taking the lead role in care delivery. AB - The NHS community services in my local area are offering free health checks. My invitation letter offered me a choice - I could take the enclosed form to my GP, get another form and go to a phlebotomy clinic, then wait 2 weeks and go back to my GP for the blood test result and the health check; or alternatively, I could go to my local pharmacy, have a blood test and assessment, all in one visit. I thought 'no contest, I am going to the pharmacy for my health check!' PMID- 22067845 TI - Coexisting pustular and ulcerative pyoderma gangrenosum. PMID- 22067846 TI - Nucleotide-binding oligomerization domain-like receptors and inflammasomes in the pathogenesis of non-microbial inflammation and diseases. AB - The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) or nucleotide-binding domain leucine-rich repeat-containing family of genes plays an important role in the development of innate immune responses. Some family members are known to form multiprotein complexes known as inflammasomes that regulate the processing and secretion of proinflammatory mediators, such as interleukin-1beta and interleukin-18. Activity of the inflammasome is triggered not only by microbial infection, but also by a wide range of both exogenous and endogenous noninfectious stimuli. Consequently, the dysregulation of inflammasome activity is associated with numerous proinflammatory, non-microbial human diseases. The discovery of NLRP3 gene mutations in autoinflammatory diseases such as Muckle Wells syndrome has led to the association of NLRs in the pathogenesis of many non microbial diseases that include arthritis, neurodegenerative disorders, metabolic disorders (obesity and diabetes), cardiovascular disease (atherosclerosis, myocardial infarction), inflammatory bowel disease, kidney disease and hypersensitivity dermatitis. A number of NLRs are also associated with human disease in the absence of inflammasome activity, suggesting additional roles for NLRs in the regulation of inflammation and disease. This review serves to provide a summary of NLR-associated diseases and, where possible, the mechanisms behind the associations. PMID- 22067847 TI - Dietary fish oil preserves cardiac function in the hypertrophied rat heart. AB - Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10 % olive oil (control) or 5 % fish oil (ROPUFA(r) 30 (17 % EPA, 10 % DHA))+5 % olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60 % depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy. PMID- 22067848 TI - Hilotherm efficacy in controlling postoperative facial edema in patients treated for maxillomandibular malformations. AB - BACKGROUND: A cooling system based on polyurethane preshaped masks for postoperative cryotherapy, named Hilotherm, has been recently introduced. The purpose of this study was to evaluate the effectiveness of this equipment in controlling postoperative edema and compare the results with those obtained with a group treated with conventional cryotherapy and a group not treated with cryotherapy. METHODS: Ninety patients were included in this randomized controlled trial. The 90 patients were divided into 3 groups. Group A was treated with Hilotherm. Group B was treated with conventional cryotherapy. Group C was not treated with cryotherapy. Using a tape measure, we measured for both sides of the face the distances in centimeters between point 0 and external canthus ([alpha]), most lateral point on the ala of the nose ([beta]), commissura labialis ([gamma]), and Pos ([delta]). We performed a Kruskal-Wallis test comparing the average variation of edema on the right and left sides of the face for each facial segment of patients of the 3 groups from time 0 to time 24 hours. RESULTS: No cryotherapy is the worst treatment for every segment studied. In anatomic regions defined [beta], [gamma], and [delta], Hilotherm was more effective in containing edema than the ice pack 24 hours after the first measurement. Opposite results were seen on district [alpha], the site not completely enclosed in the mask. CONCLUSIONS: The substantial difference between different treatments probably consisted in the greater reliability of the Hilotherm system, which is characterized by easy handling, constant temperature control, comfort, and practicality of the masks. PMID- 22067849 TI - Oral rehabilitation after surgical removal of pleomorphic adenoma. AB - Although tumors of minor salivary glands are rare, the pleomorphic adenoma is the most common pathology among the benign neoplasm and can be found with high prevalence in the junction between hard palate and soft palate. The treatment of choice for most of maxillary tumors is surgical through either a total or partial maxillectomy. However, surgical defects caused by such type of treatment lead to both clinical and psychologic disorders for the patient. The immediate oral rehabilitation using interim palate obturator after maxillectomy provides optimization on the healing process, recovers the stomatognathic functions after surgery, and avoids psychosocial sequelae for the patients. This clinical report aimed to present the rehabilitation with immediate palate obturator of a patient who underwent a partial maxillectomy due to a hard palate pleomorphic adenoma of minor salivary glands. We report the clinical importance of the prosthetic rehabilitation and the improvements on both quality of life and stomatognathic functions of this patient. It can be concluded that the immediate rehabilitation of the patient after partial maxillectomy by using an interim palate obturator was a great option and provided clinical benefits in the immediate postoperative period, improving the patient's quality of life, allowing the patient's reinsertion into society, and reducing the surgical treatment sequelae. PMID- 22067850 TI - Combined use of titanium mesh and resorbable PLLA-PGA implant in the treatment of large orbital floor fractures. AB - BACKGROUND: A variety of alloplastic permanent and resorbable materials have been successfully used in orbital floor reconstruction; nevertheless, they both have shown disadvantages in the reconstruction of large orbital floor defects. We believe that, by combining both types of implants, the disadvantages could be diminished. METHODS: This is a retrospective study that included all patients with large orbital floor defects (>2 * 2 cm), pure or in association with other facial fractures, treated in our service with the combined use of titanium mesh and the resorbable implant LactoSorb. RESULTS: We included 20 patients, 7 had pure blowout fractures and the rest had other associated maxillofacial fractures. All of them had a large orbital floor defect with entrapment of periorbital tissue and herniation into the maxillary sinus. Mean hospital stay was 2 days, and our follow-up period was for at least 3 months. Seventeen patients had complete coverage of their floor defect with restoration of orbital volume, normal globe position, and full extraocular motility. We report 3 cases of enophthalmos and 2 cases of ectropion. Follow-up tomographic scans showed incomplete implant coverage of the orbital floor in 2 cases and a misplaced implant in the other. Subsequent operation was needed for correction. CONCLUSIONS: We believe that the combination of both implants is a good option for the reconstruction of large orbital floor defects. It takes full advantage of their intrinsic properties while at the same time lowers the disadvantages of their individual use. Complications were attributed to technical errors and not to the combination of both materials. PMID- 22067851 TI - IMP3 is a novel biomarker to predict metastasis and prognosis of tongue squamous cell carcinoma. AB - Insulinlike growth factor II mRNA-binding protein 3 (IMP3) is a newly identified mRNA-binding protein that is involved in embryogenesis and carcinogenesis of some malignant tumors. The aim of this study was to investigate the clinicopathologic significance of this protein in tongue squamous cell carcinoma (SCC). The expression of IMP3 in 65 samples of tongue SCC and 27 cases of oral leukoplakia (OL) was evaluated by immunohistochemistry. These expression levels were correlated with clinical and pathologic features as well as death from tongue SCC. Weak immunohistochemical stain for IMP3 was identified in all 19 cases of OL with mild dysplasia, and no immunohistochemical reactivity was found in 8 cases of OL without dysplasia. Positive immunohistochemical stain for IMP3 was identified in 50 cases (77%) of SCC; among them, weak staining was identified in 33 cases (51%) and intermediate staining in 17 cases (26%). To compare the expression of IMP3 in tongue SCC and OL, stronger immunohistochemical reactivity was found in tongue SCC (P < 0.05). Stronger expression of IMP3 was found to be associated with lymphoid metastasis (P < 0.05) and patient poor outcome (median survival time of 40 months in the negative and weak expression group vs 10 months in the intermediate expression group; P < 0.05). This study suggests that the increase in IMP3 expression in tongue leukopathia and SCCs may play a role in the carcinogenesis and tumor metastasis of tongue SCCs. Insulinlike growth factor II mRNA-binding protein 3 could be a novel prognostic indicator for patients with tongue SCCs. PMID- 22067852 TI - Missile war injuries of the face. AB - In a society struggling to rebuild its country after 3 decades of years of dictatorships and wars, Iraqi maxillofacial and craniofacial surgeons play a critical role in treatment of many most serious terrorist missile injuries of the face by ongoing conflict in Iraq. This study reflects our surgical techniques of treating explosive missile injuries and other combat- and terrorism-related injuries and also evaluates the immediate and secondary phase managements of patients with missile injuries. This study includes 235 patients with missile war injuries of the face during a period of 4 years; all injured patients were treated in the Maxillofacial Unit of Surgical Specialties Hospital, Medical City, Baghdad. There were 195 men and 40 women; their ages ranged from 1 to 70 years (mean, 39.5 years). Posttraumatic missile facial deformities were classified as follows: 95 patients (40.43%) had bone loss; 72 patients (30.64%) had soft tissue loss; 33 patients (14.05%) had orbital injuries; and 35 patients (14.90%) had other deformities of scar contracture, fistula, and sinus formation. Two techniques were used for reconstruction of the bony defect, either by bone chips carried by osteomesh tray harvested from the iliac crest or by free block of corticocancellous bone graft from the iliac crest. Soft tissue reconstruction was done by local flaps and regional flaps such as lateral cervical and cervicofacial flaps, and the orbit was reconstructed by bone graft, lyophilized dura, and sialastic implant. Scar contracture was treated by scar revision and sinus tract excised at the same time of scar revision. In conclusion, the primary phase required an urgent airway management, controlling an active bleeding by surgical intervention; most entrance and exit wounds as well as retained missiles were located in the cheek, chin, and mandibular body, with few cases of mortality due to complications related to head injuries. The secondary phase management of deformities of the face as a complication of missile injuries was classified as bone loss, soft tissue loss, combined bone and soft tissue loss, and others (sinus tracts and poor scars). PMID- 22067853 TI - Upper double-rotation advancement method for unilateral cleft lip repair of severe forms: classification and surgical technique. AB - BACKGROUND: The purpose of this study was to evaluate the symmetry in lip height and lip width after double-rotation advancement unilateral cleft lip repair. STUDY DESIGN: This was a retrospective audit of 1 surgeon's outcome of 72 consecutively performed unilateral cleft lip with short lateral segment. Two hundred fifty patients with unilateral cleft lip were operated on using the upper double-rotation advancement technique since 2007. Of those patients, 72 met the study criterion of having anthropometric measurements performed at least 1 year postoperatively. DATA COLLECTION: Measurement of lip height, lip width, vermilion height, and alar base width was performed at the cleft and noncleft side under general anesthesia, immediately before the lip (preoperative) and palate (postoperative) surgery. The lip measurements were obtained using calipers. The matched-pair t-test analyses were performed when the assumptions required were met. When the normality assumption was not met, a nonparametric test was used, the Wilcoxon signed rank test, to assess the statistical significance of differences between the cleft side and the noncleft side. RESULTS: The study found no statistically significant differences between cleft-side and noncleft side lip height (P = 0.058), lip width (P = 0.295), and vermilion height (P = 0.237) after lip repair. CONCLUSIONS: The findings suggest that the upper double rotation and advancement technique is a good alternative to repair short lateral segment and severe forms of unilateral cleft lip. PMID- 22067854 TI - Microvascular tissue transfer in cleft palate patients: advocacy of the prelaminated radial free forearm flap. AB - The closure of wide palatal clefts and recurrent oronasal fistulae may be challenging. After repeated failure of conventional techniques, microvascular tissue transfer may be indicated in the closure of such fistulae. Depending on the location and the size of the palatal fistula, different tissues are required to sufficiently close the palatal gaps. A subdivision of common flaps into mucosa, muscular, bony, skin, and fascia flaps was carried out to analyze their suitability for alveolar, hard, and soft palate reconstruction. Furthermore, the bulk of flaps and the length of the vascular pedicle were analyzed to rate the suitability of different flaps for palatal closure. Based on a new classification of oronasal fistulae, all these factors were taken into consideration to introduce a decision guidance of what microvascular flap fits a particular clinical situation. The radial free forearm flap was found to be sufficient in the closure of all classes of oronasal fistulae. PMID- 22067855 TI - Use of stereolithographic drilling and cutting guides in bilateral mandibular distraction. AB - Mandibular distraction osteogenesis is used in the treatment of patients with syndromic and nonsyndromic class II mandibular hypoplasia. The three-dimensional distraction of the mandible is extremely complex. Past experience with mandibular distraction has demonstrated the indispensability of solid presurgical planning to achieve predictable results. We report a method for a virtual three dimensional planning of the bilateral mandibular distraction with intraoperative transfer by stereolithographic guides. Five patients (mean age, 22.8 years) with bilateral mandibular hypoplasia were examined with preoperative and postoperative computed tomographic scans. The direction and dimension of the distraction were planned on the three-dimensional computed tomographic scans. Tooth- and bone borne stereolithographic guides for transferring the planning were then applied intraoperatively. It was feasible to transfer and perform the surgery as planned by the use of the stereolithographic drilling and cutting guides. The mean distraction width was 11.33 (SD, 8.32) mm. The mean difference of the distraction width between the planning and the achieved final mandibular position was 1.80 (SD, 0.43) mm. The intercondyle distance decreased by 3.28 (SD, 1.01) mm. A parallel distraction within the planned vectors was achieved. Mandibular distraction osteogenesis in the treatment of severe mandibular hypoplasia needs careful presurgical planning. Parallel distraction and fast placement of the distractors are provided by the planning. The method provides a useful tool for both planning and intraoperative transfer of the virtually preplanned distraction vectors. PMID- 22067856 TI - Photoelastic analysis of biomechanical behavior of single and multiple fixed partial prostheses with different prosthetic connections. AB - The aim of this study was to evaluate the stress distribution on external hexagon, internal hexagon, and Morse taper implant in single and 3-unit implant supported fixed partial prostheses (FPPs) using photoelasticity. Six models were fabricated with the photoelastic resin PL-2: 3 models for the 3-unit implant supported FPP with implants of 4.0 * 10.0 mm in the region of the second premolar and molar including 1 model for each type of implant connection, and 3 models for the single prosthesis for each implant type. The prostheses fabrication was standardized. A circular polariscope was used, and axial and oblique (45 degrees) loads of 100 N were applied in a universal testing machine. The results were photographed and analyzed qualitatively. The internal hexagon implant exhibited better stress distribution and lower intensity of fringes followed by the external hexagon and Morse taper implants for the models with the 3-unit prostheses. For the single implants, the Morse taper implant presented better stress distribution, followed by the internal and external hexagon implants. The oblique loading increased the number of photoelastic fringes in all models. It was concluded that the internal hexagon implant exhibited better biomechanical behavior for the 3-unit implant-supported FPP, whereas the Morse taper implant was more favorable for the single implant-supported prosthesis. The oblique loading increased the stress in all models. PMID- 22067857 TI - Recession defects associated with scraped roots treated with subepithelial connective tissue graft. AB - The objective of the current study was to assess histomorphometrically the healing process of recession defects associated with scraped roots treated with subepithelial connective tissue graft (SCTG). Six dogs were used. Bone dehiscence defects (6 * 8 mm) and root planing were carried out on maxillary canine teeth. Following a split-mouth model, according to the treatment, left canines (control) were covered with coronally positioned flap (CPF). Right canines were submitted to treatments with SCTG. After a 3-month postoperative period, the animals were killed, and the blocks processed for the histomorphometric assessment. Data assessment demonstrated that the CPF group showed parameters of a new connective tissue attachment, length of new cement (NC), length of new bone (mean +/- SD: 0.95 +/- 0.53, 2.44 +/- 1.97, and 1.96 +/- 2.29 mm, respectively), which were higher than those of SCTG group (mean +/- SD: 0.71 +/- 0.36, 2.21 +/- 1.28, and 1.52 +/- 1.31 mm, respectively), although not significantly (P > 0.05). The length of both epithelial tissue and connective tissue apposition in the SCTG group (mean +/- SD: 1.70 +/- 0.53 and 2.62 +/- 1.52 mm, respectively) were higher than those of the CPF group (mean +/- SD: 1.18 +/- 0.49 and 2.03 +/- 1.03 mm, respectively), although showing no significant differences (P > 0.05). Within the limits of the current study, it was possible to conclude that there were no significant differences between the groups according to the histologic parameters assessed. PMID- 22067858 TI - Effect of mitomycin C on endoscopic dacryocystorhinostomy. AB - OBJECTIVE: The objectives of the study were to retrospectively analyze the efficacy of intraoperative mitomycin C (MMC) in endoscopic dacryocystorhinostomy (END-DCR) and compare it with external dacryocystorhinostomy (EXT-DCR). METHODS: For the comfort of the patients, the procedures were performed under general anesthesia. Intraoperatively during the END-DCR, we applied a cotton pledget soaked in a 0.5 mg/mL solution of MMC for 2.5 minutes. In each patient, a silicone tube was placed into the nasal cavity via the superior and inferior punctae and fixed in the vestibule. We retrospectively analyzed the medical records of patients who underwent END-DCR and EXT-DCR. RESULTS: A retrospective review was performed on the medical records of 43 patients (with a total of 49 affected cases) who were admitted to our clinics with a primary complaint of epiphora. The overall success rates were 91% in END-DCR+MMC and 71.5% in EXT-DCR. CONCLUSIONS: Mitomycin C, in appropriate doses, minimizes postoperative granulations and fibrosis. Adjunctive use of MMC is considered to increase the success rate of END-DCR. PMID- 22067859 TI - Osteoconductive capacity of hydroxyapatite implanted into the skull of diabetics. AB - Diabetes mellitus can cause various diseases, including loss of bone mineral density as a characteristic manifestation of osteoporosis. In this condition, bone is more vulnerable to pathologic fractures that can be treated by implantation of biomaterial grafts. The aim of this study was to evaluate the osteogenic capacity of hydroxyapatite implanted into bone defects in the skull of nonobese diabetic mice. Fifteen nonobese diabetic mice were divided into 3 groups: control (nondiabetic), spontaneously diabetic, and spontaneously diabetic receiving insulin replacement applied subcutaneously into the dorsum. Defects were created experimentally in the skull with a surgical bur and filled with hydroxyapatite granules. The animals were killed 4 weeks after surgery, and samples were obtained for analysis. Quantitative methods were used for measurement of the new bone formation. Data were analyzed by analysis of variance followed by the Tukey test (P < 0.05). Radiographic results showed good radiopacity of the hydroxyapatite; however, radiolucent spots were seen between the hydroxyapatite granules in the diabetic groups, indicating infiltration of connective tissue. Microscopic results showed projections of newly formed bone from the margin of bone defect toward the implant. The quantity of newly formed bone was significantly higher (P < 0.05) than that observed in the diabetic groups. The recipient area of diabetic groups contained a larger amount of connective tissue as demonstrated by radiographic analyses. In conclusion, the osteogenesis guided by the properties of hydroxyapatite may even occur in bone suffering from the effects of diabetes, but the quantity of newly formed bone is lower, and the process is slower. PMID- 22067860 TI - Rugby players' awareness of concussion. AB - PURPOSE: Concussion is a common issue in most contact sports, such as rugby, being one of the most troublesome injuries facing the sports medicine physician. The aim of this article was to survey the knowledge and beliefs concerning concussion in a sample of young rugby athletes in the northwest of Italy. METHODS: The athletes of 4 amateur rugby teams completed a questionnaire about their knowledge about the signs and symptoms of concussion and of return-to-play strategies and protocols. RESULTS: Twenty-five athletes reported that they had not been informed by anyone about symptoms of concussion and its consequences. Among these, 7 players thought they could return to play immediately after a concussion during the very same match. CONCLUSIONS: The surveyed group in this study presented a general lack of knowledge of concussion. Rugby athletes and coaches must be made aware about signs and symptoms of concussion to suspect this injury. It would be desirable that rugby players are educated regarding the potential risks of playing while symptomatic. PMID- 22067861 TI - Analysis of short implants and lateralization of the inferior alveolar nerve with 2-stage dental implants by finite element method. AB - There are difficulties for dental implant use in posterior mandible when there is little bone height for implant placement. Among the treatment alternatives available, there is no direct comparison between short implants and conventional implants placed with lateralization of the inferior alveolar nerve. The present study aimed to comparatively evaluate the risk of peri-implant bone loss of the above treatments. With this aim, computed tomography scans of mandibles were processed, and implants and prosthetic components were reverse engineered for reconstruction of three-dimensional models to simulate the biomechanical behavior of 3-element fixed partial dentures supported by 2 osseointegrated implants, using simulations with the finite element method. The models of implants were based on MK III implants (Nobel Biocare) of 5- and 4-mm diameter by 7-mm length, representing short implants, and 4- and 3.75-mm diameter by 15-mm length, representing implants used in lateralization of the inferior alveolar nerve. All models were simulated with prestress concerning the stresses generated by the torque of the screw. Axial and oblique occlusal loads at 45% were simulated, resulting in 8 different simulations. The results showed that the risk for bone loss in osseointegrated implants is greater for treatments with short implants. PMID- 22067862 TI - Evaluation of the nose profile after maxillary advancement with impaction surgeries. AB - OBJECTIVE: The aim of this study was to identify and quantify nasal profile changes following maxillary advancement (MA) and maxillary advancement with impaction (MAI) with Le Fort I osteotomies. METHODS: The study consisted of preoperative and postoperative lateral cephalograms of 42 class III adult patients. The study sample was divided into 2 groups, with the first group composed of 22 patients who underwent MA surgery and the second group composed of 20 patients who underwent MAI surgery. In total, 7 skeletal parameters and 17 soft-tissue parameters related to nasal projection, hump, dorsal convexity, and the nasolabial region were evaluated on the cephalograms, and hard- and soft tissue relationships were assessed. RESULTS: Nasal length, hump, nasal depths, distance from the most convex point of the Alar curvature to the most inferior point of the nostril, alar curvature-subnasale, and subnasale-pronasale measurements decreased postoperatively. In the MAI group, MA correlated with significant decreases in nasal length and hump. In the MA group, MA correlated with pronasale position (P < 0.05); significant decreases in nasal depth, columella convexity, and subnasale-pronasale length; and significant changes in subnasale position. CONCLUSIONS: There is little difference in the effects of the 2 different maxillary surgeries on the postoperative nasal profile. PMID- 22067863 TI - Upper lip asymmetry perception using three-dimensional anthropometry in patients with unilateral cleft lip deformity. AB - Conventional anthropometry using photographs has been widely used, but it does not provide accurate length. For upper lip asymmetry analysis, three-dimensional photographic system (3D VECTRA; Canfield, Fairfield, NJ) was used to calculate the ratio of cleft-side and noncleft-side curvature lengths. Thirty patients with unilateral cleft lip were analyzed. Three-dimensional photographic system was used to calculate the length ratio of upper lip of cleft and noncleft sides. In addition, two-dimensional photographs were analyzed by 10 plastic surgeons, and upper lip asymmetry was scored using a visual analog scale (VAS). Pearson analysis was used to identify relations between the ratios and the VAS scores. Intrarater reliability for the VAS scores ranged from 0.653 to 0.925, and interrater reliability was 0.611. Pearson correlation coefficients for each ratio and the VAS score were 0.412 (P = 0.024) for cleft-side to noncleft-side curvature length ratio of Cupid's bow, 0.250 (P = 0.182) for cleft-side to noncleft-side curvature length ratio from the commissure to the lowest point of the nasal ala, 0.214 (P = 0.018) for linear length ratio of Cupid's bow, and 0.356 (P = 0.153) for linear length ratio from the commissure to the lowest point of the nasal ala. Analysis of upper lip asymmetry in unilateral cleft lip patients using the three-dimensional photographic system is more accurate than two-dimensional anthropometry. Horizontal curvature length ratio was the most strongly correlated with VAS score. PMID- 22067864 TI - Elongated styloid process associated with nevoid basal cell carcinoma syndrome. AB - This article presents a case with nevoid basal cell carcinoma syndrome (NBCCS) and an elongated styloid process. Basal cell carcinoma syndrome, also known as Gorlin-Goltz syndrome, is an autosomal dominant inherited syndrome manifested by multiple defects involving the skin, nervous system, eyes, endocrine system, and bones. Elongated styloid process or calcified stylohyoid ligament cause craniofacial or cervical pain. The actual cause of elongation of the styloid process or the calcification of the stylohyoid ligament is unclear. The cause of elongation of styloid process in this case may be the calcification induced by NBCCS. This report is the first case presentation of NBCCS with elongated styloid process. Elongated styloid process might be described as an anomaly of an NBCCS. PMID- 22067865 TI - Mimix hydroxyapatite cement use in the reconstruction of the craniofacial skeleton. AB - Reconstruction of the craniofacial skeleton has undergone a significant evolution during the past century. Initially, the use of autogenous bone grafts from various sites was the criterion standard. However, owing to donor site morbidity and lack of sufficient bone for large defects, surgeons have relied on various bone substitutes. Hydroxyapatite (HA) has served as an alternative to autogenous grafts, but questions regarding biocompatibility, risk of infection, and slow set times have hampered its acceptance. This article serves as a review of a single surgeon's experience using HA in the craniofacial skeleton. Eighteen patients receiving HA between March 2000 and November 2006 were observed. Sixteen underwent recontouring of skull-based bone defects, and 2 underwent recontouring for nasal and alveolar defects. The mean amount of HA used in each patient was 30.2 g. For large contour irregularities, the maximum thickness of HA used was 8 mm. The size of bone defects ameliorated averaged 4.8 cm(2). Complications occurred in 3 (16.7%) of 18 patients and included scalp hematoma and superficial cellulitis. In addition, 1 patient developed a facial abscess after placement along the alveolar floor, which necessitated removal. Hydroxyapatite represents a viable alternative to autogenous bone grafts when used in the correct manner. Hydroxyapatite should be used only for smaller defects or used in conjunction with absorbable plates when attempting to fill larger defects. Use of HA for nasal piriform augmentation or alveolar bone grafting should not be considered owing to problems with late infections. PMID- 22067866 TI - Worldwide incidence of odontogenic tumors. AB - PURPOSE: The objective of the study was to determine the relative frequency of odontogenic tumors (OTs) in the world population, directing an epidemiologic profile to these lesions. METHODS: Was conducted a search in epidemiologic studies involving OTs that are listed by PubMed and Ovid, EMBASE, and Cochrane Library, embracing the period from January 1960 to January 2010, to verify their incidence worldwide. We identified 195 articles, of which 19 articles were selected, considering the location, age, sex, histologic type, and World Health Organization classification. RESULTS: A total of 8544 OTs were found. The results showed a low frequency of malignant OTs in selected works. The most frequent tumor was ameloblastoma (39.6%), followed by odontoma (20.1%) and the newly included keratocystic OT (13.8%). CONCLUSIONS: These OTs are uncommon lesions in world population, and malignant OTs are very rare. The relative frequency of different kinds of OTs, the age, and the sex distribution show a marked geographic variation in incidence of those lesions. This was particularly notable in the ameloblastomas and odontoma, with the incidences being relatively well and weighted showing similar values to an average when compared with previous studies. PMID- 22067867 TI - Microdeletion 3q syndrome. AB - The authors present the clinical case of a 5-month-old boy, affected by multimalformative syndrome with features of microdeletion 3q syndrome. In the literature so far, the real incidence is unknown because of its rarity. The goal of this study was to describe the salient findings of this rare malformative syndrome, which needs a multidisciplinary approach. The patient had 3q interstitial chromosome deletion (q22.1-q25.2). He showed the following clinical features: microcephaly, microphthalmia, epicantus inversus, blepharophimosis, palpebral ptosis, short neck with pterygium, brachycephaly, round face, hypotelorism, broad nasal bridge, beaked nose, large and low-set ears, soft cleft palate, retromicrognathia with large mouth, arthrogryposis of the superior limbs and knees in association with clinodactyly, overlapping of second and third digits of both hands and feet, and gastroesophageal reflux. The patient developed physical and motor development delay. He was affected by Dandy-walker malformation, characterized by cerebellum vermis hypoplasia. The placement of the patient in contiguous gene syndrome (Dandy walker syndrome, Pierre-Robin sequence, and Seckel syndrome) was carried out by a multidisciplinary team to have a holistic evaluation of clinical findings. Thanks to this approach, it was possible to establish a complete diagnostic and therapeutic course. The genetic analysis enables to arrange an assistive program. Surgeons' attention was focused on the malformations, which represented an obstacle for normal development and social life. PMID- 22067868 TI - Clinical and immunohistochemical analysis of orbital metastasis from prostate carcinoma. AB - Orbital tumors can present with different symptoms, especially ophthalmic disturbances. We describe 1 patient with an orbital metastasis from prostate carcinoma presenting with proptosis and give details of his presentation, diagnostic tools, and treatment. This is a rare case. Possible ocular spread of prostate adenocarcinoma and the diagnostic techniques used are discussed. It is stressed that immunohistochemical studies and comparison with primary tumor may be essential for a definitive diagnosis. The treatment of prostate orbital metastases is also reviewed. PMID- 22067869 TI - Evaluation of stress patterns produced by implant-retained overdentures and implant-retained fixed partial denture. AB - The purposes of this study were to photoelastically measure the biomechanical behavior of 4 implants retaining different cantilevered bar mandibular overdenture designs and to compare a fixed partial denture (FPD). A photoelastic model of a human edentulous mandible was fabricated, which contained 4 screw-type implants (3.75 * 10 mm) embedded in the parasymphyseal area. An FPD and 3 overdenture designs with the following attachments were evaluated: 3 plastic Hader clips, 1 Hader clip with 2 posterior resilient cap attachments, and 3 ball/O-ring attachments. Vertical occlusal forces of 100 N were applied between the central incisor and unilaterally to the right and left second premolars and second molars. Stresses that developed in the supporting structure were monitored photoelastically and recorded photographically. The results showed that the anterior loading, the overdenture with 3 plastic Hader clips, displayed the largest stress concentration at the medium implant. With premolar loading, the FPD and overdenture with 3 plastic Hader clips displayed the highest stresses to the ipsilateral terminal implant. With molar loading, the overdenture with 3 ball/O-ring attachments displayed the most uniform stress distribution in the posterior edentulous ridge, with less overloading in the terminal implant. It was concluded that vertical forces applied to the bar-clip overdenture and FPD created immediate stress patterns of greater magnitude and concentration on the ipsilateral implants, whereas the ball/O-ring attachments transferred minimal stress to the implants. The increased cantilever in the FPD caused the highest stresses to the terminal implant. PMID- 22067870 TI - Murine RANK protein's inhibition of bone resorption. AB - OBJECTIVE: The objective was to study the inhibitory effects of recombinant murine receptor activator of nuclear factor kappaB (RANK) protein on osteoclasts in vivo and in vitro. METHODS: The RANK protein was added to the cocultures of osteoclasts at concentrations of 10(-6), 10(-5), and 10(-4) g/L. The morphology and number of osteoclasts were examined. Female KM mice were ovariectomized and treated with RANK protein at 5 mg/kg body weight. Biochemical markers of bone metabolism, bone mineral density, and bone morphology were examined. RESULTS: Three days after RANK treatment, the numbers of tartrate-resistant acid phosphatase-positive osteoclasts and resorption pits in bone slices decreased significantly in each treatment group, with the most significant decrease observed in the 10(-4) g/L group. Compared with the control group in vivo, the RANK-treated group exhibited higher bone mineral density and nearly complete inhibition of tartrate-resistant acid phosphatase-positive osteoclasts in bone slices. CONCLUSIONS: Recombinant murine RANK protein effectively inhibits the activity of osteoclasts and the resulting bone resorption. PMID- 22067871 TI - Complex craniofacial reconstruction with prostheses as an alternative method to autogenous reconstruction. AB - Reconstruction of facial organ and tissue losses using autogenous tissue is a permanent and effective method in plastic surgery. However, in cases where the patient's general condition does not allow for surgical reconstruction or where the patient is in need of reconstruction of complex organs such as the eye, nose, or ear, an epithesis can be considered as an alternative to treatment with autogenous tissue. The purpose of this study was to investigate the factors affecting the success rate of facial reconstructions with an externally retained prosthesis in relation to the defect location and radiotherapy treatment. Between September 2004 and October 2008, 11 patients with facial tissue defects who had been treated with an osseointegrated implant system were evaluated. Because 1 patient with a midfacial defect died 3 months after the surgery, this case was excluded, leaving a total of 10 patients for evaluation. Five patients' facial defects were located in the ear, 2 patients had nasal defects, and 3 patients had defects in the midfacial region. The total numbers of implants applied to these regions were 13, 6, and 25, respectively. A total of 44 implants applied were followed for an average period of 52.4 months (between 6 and 77 months). In cases where the reconstruction was considered satisfactory, no infections were observed, and there were no implant losses in the mastoid region. Implant losses were observed in a total of 14 implants (31.8%), 2 of which were in the glabellar region (4.5%), and 12 were in the midfacial region (27.2%). The implant losses were observed between the first and 18th postsurgical months (with an average of 6 months). The remaining implants were sufficient to retain the prostheses. Because of these results, the use of implant-assisted epitheses can be considered a viable alternative in patients whose facial defects cannot be corrected through reconstructive surgery performed with autogenous tissue. PMID- 22067872 TI - Mandibular sagittal split osteotomy: is a bicortical 2-screw osteosynthesis adequate? AB - The aim of this study was to prospectively evaluate the accuracy and reliability of the use of the Hunsuck/Epker-type mandibular split osteotomy together with osteosynthesis with placement of 2 bicortical positioning screws without the adjunctive use of a postoperative maxilla-mandibular fixation in the treatment of mandibular dentofacial deformities. We analyzed the clinical and radiologic data of 54 patients with dentofacial deformities. We recorded age and sex, status of healing, and complications. Postsurgical complications that were recorded as minor did not require surgical intervention, whereas major complications required further surgical intervention. Fifty-one patients (94.5%) had a successful treatment outcome without complications, 13 patients (24%) developed minor complications, and 3 patients (5.5%) developed screw loosening requiring hardware removal and reosteosynthesis. The present study has demonstrated that Hunsuck/Epker-type mandibular split osteotomy together with osteosynthesis with placement of 2 bicortical positioning screws without the adjunctive use of a postoperative maxilla-mandibular fixation in the treatment of mandibular dentofacial deformities results in a low rate of major complications with a high rate of success PMID- 22067873 TI - Calcium hydroxide mixed with camphoric p-monochlorophenol or chlorhexidine in delayed tooth replantation. AB - This study evaluated the repair process after delayed replantation of rat teeth, using calcium hydroxide (Ca(OH)2) mixed with camphorated p-monochlorophenol (CMCP), chlorhexidine 2% (CHX), or saline as temporary root canal dressing to prevent and/or control inflammatory radicular resorption. Thirty Wistar rats (Rattus norvegicus albinos) had their right upper incisor extracted, which was bench-dried for 60 minutes. The dental papilla, the enamel organ, the dental pulp, and the periodontal ligament were removed. The teeth were immersed in 2% acidulated-phosphate sodium fluoride solution for 10 minutes. The root canals were dried with absorbent paper cones and divided into 3 groups of 10 animals according to root canal dressing used: group 1: Ca(OH)2 + saline, group 2: Ca(OH)2 + CMCP, and group 3: Ca(OH)2 + CHX 2%. Before replanting, the teeth sockets were irrigated with saline. Histological analysis revealed the presence of inflammatory resorption, replacement resorption, and ankylosis in all 3 groups. Statistical analysis showed a significant difference between group 3 and the other groups. The use of Ca(OH)2 mixed with CMCP or CHX did not show an advantage over the use of Ca(OH)2 mixed with saline in preventing and/or controlling inflammatory resorption in delayed replantation of rat teeth. PMID- 22067874 TI - Defining the protruding ear. AB - OBJECTIVE: Although protruding ears are one of the most frequently occurring congenital deformities in the craniofacial area, there is no clear consensus in literature as to the definition. Our aim was to provide a clear delineation for the definition of prominent ears, deduced from the anthropometry of normal (nonprotruding) ears. METHODS: We performed a prospective cohort study to assess the anatomy of the normal auricle in children using computer-assisted anthropometry in photographs of 102 children aged 5 to 18 years. We compared the anatomy to retrospectively assess photographs of 44 patients who were listed for prominent ear correction. RESULTS: Our results show that protrusion differs statistically between sexes. In view of these data, an ear could be defined as prominent when the upper protrusion exceeds 21.5 mm or the lower protrusion exceeds 20.0 mm in boys and the upper protrusion exceeds 17.5 mm or the lower protrusion exceeds 15.5 mm in girls. Using these demarcations, 87.5% of our operated prominent ears would qualify as a prominent ear. In addition, we found that prominent ears have larger auricular lengths and consequently larger surface measurements compared with normal ears (P = 0.001). Up to 19.3% of the normal ears showed an asymmetry of more than 3 mm concerning protrusion. CONCLUSIONS: Protrusion differs significantly between sexes. This indicates that different criteria should be used to judge protrusion in boys and girls. None of our prominent ears exceeded only the demarcation in the lower protrusion, suggesting that upper protrusion plays a larger role in the perception of prominence than lower protrusion and should therefore be the main objective of corrective otoplasty. Furthermore, the variation of asymmetry of protrusion in the normal population indicates that an often used success criteria in otoplasty of an asymmetry less than 3 mm may be too strict. PMID- 22067875 TI - Intraoral curved ostectomy for prominent mandibular angle by grinding, contiguous drilling, and chiseling. AB - There are several surgical techniques for mandibuloplasty, for example, ostectomy of the lateral cortex around the mandibular angle, angle-splitting ostectomy, sagittal split ramus ostectomy, multistage osteotomy of the mandibular angle. These techniques all have achieved excellent aesthetic results, but they require a high level of skill and are time consuming. From July 1995 to June 2010, a total of 1006 patients underwent intraoral curved ostectomy for prominent mandibular angle by grinding, contiguous drilling, and chiseling in our department. A round bur was used to reduce the outer cortex thickness of the mandible body. The ostectomy line on the mandibular angle was penetrated contiguously using a long-shaft bur drill. A curved-headed chisel approximately 10 mm in width was hammered to separate the redundant mandibular angle. Concurrent procedures such as reduction malarplasty and genioplasty were performed in patients with protrusion of the malar bone and microgenia. A total of 992 patients were satisfied with the final facial contour. The square-shaped appearance was converted to an ovoid, slender, and feminine facial contour from the frontal view. Ninety-three patients underwent postoperative complications. Among the 93 cases, there were 14 patients who were unsatisfied with the final results. The average operative time was 42 minutes for ostectomy of prominent mandibular angle. Intraoral curved ostectomy for prominent mandibular angle by grinding, contiguous drilling, and chiseling is an appropriate technique for correcting lower facial contour. The surgical technique is not complex, and the ostectomy is easy to manipulate. The operation consumes less time. Complications of various degrees are relatively lower, and most of them can be treated effectively. Both surgeons and most of the patients are satisfied with the results. PMID- 22067877 TI - Renal system. PMID- 22067876 TI - Retinoic acid pathway activity in Wilms tumors and characterization of biological responses in vitro. AB - BACKGROUND: Wilms tumor (WT) is one of the most common malignancies in childhood. With current therapy protocols up to 90% of patients can be cured, but there is still a need to improve therapy for patients with aggressive WT and to reduce treatment intensity where possible. Prior data suggested a deregulation of the retinoic acid (RA) signaling pathway in high-risk WT, but its mode of action remained unclear. RESULTS: The association of retinoid signaling and clinical parameters could be validated in a large independent tumor set, but its relevance in primary nephrectomy tumors from very young children may be different. Reduced RA pathway activity and MYCN overexpression were found in high risk tumors as opposed to tumors with low/intermediate risk, suggesting a beneficial impact of RA especially on advanced WT. To search for possible modes of action of retinoids as novel therapeutic options, primary tumor cell cultures were treated in vitro with all-trans-RA (ATRA), 9cis-RA, fenretinide and combinations of retinoids and a histone deacetylase (HDAC) inhibitor. Genes deregulated in high risk tumors showed opposite changes upon treatment suggesting a positive effect of retinoids. 6/7 primary cultures tested reduced proliferation, irrespective of prior RA signaling levels. The only variant culture was derived from mesoblastic nephroma, a distinct childhood kidney neoplasm. Retinoid/HDAC inhibitor combinations provided no synergistic effect. ATRA and 9cis-RA induced morphological changes suggestive of differentiation, while fenretinide induced apoptosis in several cultures tested. Microarray analysis of ATRA treated WT cells revealed differential expression of many genes involved in extracellular matrix formation and osteogenic, neuronal or muscle differentiation. The effects documented appear to be reversible upon drug withdrawal, however. CONCLUSIONS: Altered retinoic acid signaling has been validated especially in high risk Wilms tumors. In vitro testing of primary tumor cultures provided clear evidence of a potential utility of retinoids in Wilms tumor treatment based on the analysis of gene expression, proliferation, differentiation and apoptosis. PMID- 22067878 TI - Worldwide demand for critical care. AB - PURPOSE OF REVIEW: Interest in the global burden of critical illness is growing, but comprehensive data to describe this burden and the resources available to provide care for critically ill patients are lacking. RECENT FINDINGS: Challenges to obtaining population-based global estimates of critical illness and resources to treat it include the syndrome-based definitions of critical illness, incorrect equating of 'critical illness' with 'admission to an intensive care unit', lack of reliable case ascertainment in administrative data, and short prodrome and high mortality of critical illness, limiting the number of prevalent cases. Modeling techniques will be required to estimate the burden of critical illness and disparities in access to critical care using existing data sources. Demand for critical care is likely to increase, related to urbanization, an aging demographic, and the ongoing wars, disasters, and pandemics, whereas economic crises will likely decrease the ability to pay for it. SUMMARY: Major unexplored research and public health questions remain unanswered regarding the worldwide burden of critical illness, variation in resources available for treatment, and strategies to prevent and treat critical illness that are broadly effective and feasible. PMID- 22067879 TI - Remote care by telemedicine in the ICU: many models of care can be effective. AB - PURPOSE OF REVIEW: Telemedicine, by the use of audiovisual technologies, is increasingly being used to assist in patient care by ICUs unable to be staffed by consultant intensivists. This review discusses the recent evaluation of these services and their potential role in managing intensive care patients. RECENT FINDINGS: Models of care range from complete remote 24 h surveillance requiring direct video observation to a consultation liaison service only requiring conventional telephone links. There has been a rapid adoption of such services especially in North America where access to on-site intensive care specialists is limited for the volume of intensive care being undertaken. Early work suggests savings in terms of cost and length of stay with an improvement in compliance with care protocols. However, later work is not as supportive of such services, possibly related to differing care infrastructures and the organization of individual units. The key task is to ascertain the most appropriate service requirements that would assist in care for a given patient circumstance. SUMMARY: Clear benefits of ICU-telemedicine systems remain unclear but at least the systems appear safe. Formal reviews of the impacts and contribution of ICU telemedicine to processes of care, the effects on unit staffing, hospital organization, and the healthcare region are needed. However, ICU-telemedicine is available and being embraced by some, especially to deal with the tyranny of distance. PMID- 22067880 TI - Current world literature. PMID- 22067882 TI - A high court of wound care? AB - I have just arrived back from two very enjoyable (albeit rainy) days in Galway, attending the Wound Management Association of Ireland's biennial conference. The title of one of the sessions, 'The great debate: technology versus dressings in wound management - is there a difference in outcomes?', caught my eye. Interestingly, while listening to the proceedings, it became apparent that there was more consensus than debate among the delegates, with most agreeing that the key to success is simply the ability to identify which option is most suited to the needs of the patient and wound. Ironically, given that we were talking about new technology, the old phrase 'back to basics' was used repeatedly, referring in this instance to the need for thorough and holistic assessment. Plus ca change, plus c'est la meme chose! PMID- 22067883 TI - Quantitative estimation of exudate volume for full-thickness pressure ulcers: the ESTimation method. AB - OBJECTIVE: To develop an equation for the estimation of exudate volume in millilitres, for full-thickness pressure ulcers, according to wound characteristics. METHOD: In a cross-sectional study, 41 patients aged >60 years with 58 full-thickness pressure ulcers were evaluated. Exudate was collected by covering each wound with a transparent occlusive dressing and the accumulated volume was measured to estimate volume per day. The overall severity of each wound was evaluated by the DESIGN-R tool; a model was then developed to estimate the volume of exudate based on these experimental values. Linear regression analyses were performed to evaluate the precision and accuracy of the model. RESULTS: The model, including exudate score, size score, and total score, showed a higher adjusted coefficient of determination (R2=0.66) than the model with only a traditional exudate score (R2=0.57). After adjustment for age, inclusion of interaction terms, and modification of bias, a model with continuous parameters was finally developed: exudate volume per day (ml/day) = exp([0.86*exudate score]+ [0.21*size score]+[0.12*total score]-[0.013*size score*total score] [0.04*age]-3.60). Furthermore, a categorical model was developed for clinical simplicity of use. The adjusted R2 was increased to 0.73 for the continuous model and to 0.77 for the categorical model. There were no apparent biases (p>0.05) and no correlations between residuals and measured value (p>0.05) in these models. CONCLUSION: The equation, including the exudate score, size score and total score of DESIGN-R, as well as age, is called the ESTimation method. It will be useful for clinicians to predict the absolute volume of exudate and to select appropriate dressings for full-thickness pressure ulcers. DECLARATION OF INTEREST: The authors have nothing to declare. PMID- 22067884 TI - Modelling the cost-effectiveness of electric stimulation therapy in non-healing venous leg ulcers. AB - OBJECTIVE: To estimate the cost-effectiveness of using electric stimulation (ES) therapy (Accel-Heal) plus dressings and compression bandaging compared with dressings and compression bandaging alone in treating chronic, non-healing venous leg ulcers (VLUs) of >6 months' duration from the perspective of the National Health Service (NHS) in the UK. METHOD: A 5-month Markov model was constructed, depicting the management of a chronic, non-healing VLU of >6 months' duration. The model considers the decision by a clinician to continue with a patient's previous care plan (comprising dressings and compression bandaging) or treating with ES therapy plus dressings and compression bandaging. The model was used to estimate the relative cost-effectiveness of ES therapy at 2008-2009 prices. RESULTS: According to the model, 38% of VLUs are expected to heal within 5 months after starting ES therapy, with a further 57% expected to improve. This improvement in clinical outcome is expected to lead to a 6% health gain of 0.017 QALYs (from 0.299 to 0.316 QALYs) over 5 months. The model also showed that using ES therapy instead of continuing with a patient's previous care plan is expected to reduce the NHS cost of managing them by 15%, from L880 to L749, due in part to a 27% reduction in the requirement for nurse visits (from mean 49.0 to 35.9 visits per patient) over the first 5 months after the start of treatment. Hence, use of ES therapy was found to be a dominant treatment (improved outcome for less cost). CONCLUSION: Within the model's limitations, use of ES therapy potentially affords the NHS a cost-effective treatment, compared with patients remaining on their previous care plan in managing chronic, non-healing VLUs of >6 months' duration. However, this is dependant on the number of ES therapy units per treatment, the unit cost of the device, and the number of nurse visits required to manage patients in clinical practice. DECLARATION OF INTEREST: This study was sponsored by Synapse Microcurrent Ltd., manufacturers of Accel-Heal. The authors have no other conflicts of interest that are directly relevant to the content of this manuscript. In particular, Synapse Microcurrent Ltd. had no role in the study design, in the collection, analysis and interpretation of data, or in writing the manuscript. PMID- 22067885 TI - Effect of simulated leg length discrepancy on plantar pressure distribution in diabetic patients with neuropathic foot ulceration. AB - OBJECTIVE: To study the effect of a minor degree of artificially induced leg length discrepancy (LLD) on plantar pressure distribution in diabetic patients with neuropathic foot ulceration. METHOD: In-shoe plantar pressure distributions were measured on the ulcerated foot during walking using F-scan (Tekscan Inc.). To simulate minor LLD, the contralateral leg length was changed by asking patients to walk under three different conditions: wearing shoe of the same sole thickness (NLLD), walking with a bare foot (20mm long leg) and wearing a 40mm high platform-sole shoe (20mm short leg). These three different walking conditions were compared in a randomised, single-blinded crossover design. RESULTS: The study included 28 diabetic patients with neuropathic foot ulcers (53.7 +/- 6.8 years; 16 males, 12 female). Notably, the peak pressure and pressure time integral (PTI) were the most affected parameters. PTI significantly increased beneath total foot, mid-foot, 2nd, 3rd, 4th and 5th metatarsal heads (MTHs), and 3rd toe, when the 20mm short leg was simulated (79.4 +/- 21.1; 61.5 +/- 32.3; 59.9 +/- 36.5; 69 +/- 42.1; 70.6 +/- 42.3; 63.9 +/- 33.7; 40.+/- 33.2 kPa.s, respectively), compared with NLLD (73.7 +/- 19.9; 55.524; 51.8 +/- 30.1; 58.4 +/- 37.6; 60.3 +/- 39.5; 57.2 +/- 32.3; 36.9 +/- 33.3 kPa.s, respectively). CONCLUSION: The short leg of diabetic patients with neuropathic foot ulcers will be subjected to greater pressure load, primarily beneath the total foot, mid-foot and 2nd, 3rd, 4th and 5th metatarsal heads. As such, care should be taken to avoid minor LLD, as it could inadvertently develop on using offloading devices. DECLARATION OF INTEREST: The authors have nothing to declare. PMID- 22067886 TI - The MOEWAT as a proposed method of evaluating orbital exenteration wounds. AB - Orbital exenteration is a disfiguring and life-changing surgical procedure that involves the removal of the socket contents, including the eye, surrounding adnexa and, in some cases, the eyelids, orbital bone and sinuses. Wound healing of exenterated sockets can be complex and may take several months to completely heal. In an attempt to provide a framework for continuity of care for patients who undergo orbital exenteration surgery, we propose a socket wound assessment tool, which will allow professionals to track changes in orbital exenteration wounds. The Manchester Orbital Exenteration Wound Assessment tool (MOEWAT) has been developed to facilitate assessment and evaluation of postoperative exenterated sockets at any given time. Consequently, as the first assessment instrument specifically developed for use in orbital exenterated patients, the MOEWAT could provide a basis for wound-care decision-making in relation to clinical findings. PMID- 22067887 TI - The effect of temperature and humidity on the permeability of film dressings. AB - The moisture vapour permeability of a dressing can make an important contribution to its overall fluid handling capacity. Despite the fact that this parameter is often quoted in scientific literature and manufacturers' promotional material, it is a concept that is not generally well understood. In particular, the effect of changing environmental conditions upon experimentally determined permeability values for particular dressings is rarely acknowledged. The present study was undertaken to derive and validate a method that could be used to predict the permeability of a self-adhesive semipermeable film dressing under specific conditions of temperature and humidity using a single set of data generated in the laboratory. A calculator that facilitates this process is also described. PMID- 22067888 TI - Complex lower extremity wounds treated with skin grafts and NPWT: a retrospective review. AB - OBJECTIVE: To evaluate a single centre experience with the use of NPWT for securing split-thickness skin grafts in the management of specifically lower extremity chronic wounds, including revascularised arterial wounds, amputations, diabetic and venous leg ulcers. METHOD: A seven-year retrospective review of a prospectively maintained database of all the patients who underwent primary split thickness skin grafts (STSGs) with immediate postoperative NPWT for at least 96 hours was carried out. The percentage graft take after removal of NPWT device and clinical follow-up date were reviewed. RESULTS: A total of 59 skin grafts procedures had adequate follow up to be reviewed. This included 39% post debridement/ amputation wounds in patients who presented with diabetic foot infection/gangrene, 31% venous leg ulcers, and 31% other post-surgical wounds (arterial ulcers that had undergone revascularisation). The mean percentage graft survival after removal of V.A.C. was 94%; 63% of cases had complete graft survival, 25% had 90-99% survival, and 8.5% had 80-89% survival. Outpatient follow up ranged from 2 weeks to 5 years (mean of 10 months). Fifteen per cent of patients were lost to follow up, and, of the remaining patients, 76% remained completely healed, 10% remained partially healed, and 14% lost the entire STSG. CONCLUSION: Patients with STSGs secured with NPWT required fewer repeated grafting procedures, had very high initial graft survival with complete recipient bed coverage, and had good long-term wound closure rates compared with historical controls. While retrospective reviews, such as this, support NPWT as a good method of STSG affixation, the paucity of reviews with other study designs does not allow for good historic comparison, so a well-enrolled prospective trial would be of use. DECLARATION OF INTEREST: Dr J.C. Lantis is a member of the speakers' bureau, has been a site principal investigator of four multicentre trials and has been a consultant for KCI Inc. The same author has no equity in the company and has no financial benefit from positive results for the company's product(s). No external funding was sought nor obtained for this study. PMID- 22067889 TI - The potential role of preventing atherosclerosis by induction of neonatal tolerance to VLDL. AB - Induction of immune tolerance to ox-LDL could reduce atherosclerosis by modulation immune response. We suppose that very low density lipoprotein (VLDL) may have a similar role to ox-LDL in autoimmune response of atherosclerosis. In this study, neonatal rats were injected with ox-LDL, VLDL, or equal-volume saline, respectively. Vaccination with ox-LDL reduced the level of specific antibody, T cells proliferation response, and the level of endothelins. The method also had a tendency of reducing blood lipids. Vaccination with VLDL obviously reduced the level of specific antibody and T cells proliferation. Though there was also a tendency of reducing blood lipids and endothelins, the effect was less prominent than that with ox-LDL. We conclude that, although the effect was less obvious, vaccination with VLDL to induce neonatal tolerance had an effect on modulating immune response, protecting endothelial cells, and reducing blood lipids. PMID- 22067897 TI - Migraine- and dystonia-related disease-mutations of Na+/K+-ATPases: relevance of behavioral studies in mice to disease symptoms and neurological manifestations in humans. AB - The two autosomal dominantly inherited neurological diseases: familial hemiplegic migraine type 2 (FHM2) and familial rapid-onset of dystonia-parkinsonism (Familial RDP) are caused by in vivo mutations of specific alpha subunits of the sodium-potassium pump (Na(+)/K(+)-ATPase). Intriguingly, patients with classical FHM2 and RDP symptoms additionally suffer from other manifestations, such as epilepsy/seizures and developmental disabilities. Recent studies of FHM2 and RDP mouse models provide valuable tools for dissecting the vital roles of the Na(+)/K(+)-ATPases, and we discuss their relevance to the complex patient symptoms and manifestations. Thus, it is interesting that mouse models targeting a specific alpha-isoform cause different, although still comparable, phenotypes consistent with classical symptoms and other manifestations observed in FHM2 and RDP patients. This review highlights that use of mouse models have broad potentials for future research concerning migraine and dystonia-related diseases, which will contribute towards understanding the, yet unknown, pathophysiologies. PMID- 22067898 TI - Does surgery for breast cancer induce angiogenesis and thus promote metastasis? AB - At the time of surgery for breast cancer, cancer cells released from the primary tumor have most likely entered blood or lymphatic vessels, leading to the development of micrometastases. Cancer cells directly produce angiogenesis stimulators, provoke the release of stimulators bound to the surrounding extracellular matrix and induce macrophages to secrete angiogenesis stimulators, thereby promoting angiogenesis. Metastasis dormancy is characterized by a balance between cell proliferation and apoptosis and is thought to be controlled by increased apoptosis, indirectly induced by angiogenesis inhibitors. Many patients with solid tumors already have micrometastases at the time of detection and surgical removal of their primary tumors. Primary tumor resection is believed to stimulate angiogenesis, initiating the proliferation of latent micrometastases. Latent micrometastases have already acquired angiogenic potential. The provision of additional therapy to inhibit angiogenesis after surgery is therefore considered a rational approach. The effectiveness of dormancy therapy should be evaluated in the prospective clinical trials of chemotherapy with drugs such as cyclophosphamide and UFT, which have been reported to inhibit angiogenesis as demonstrated by the numbers of circulating endothelial cells and circulating endothelial progenitors in peripheral blood before and after surgery in women with primary breast cancer. PMID- 22067899 TI - An Observational Study of the Etiology, clinical presentation and outcomes associated with peritonitis in Lilongwe, Malawi. AB - INTRODUCTION: Peritonitis is a life-threatening condition with a multitude of etiologies that can vary with geographic location. The aims of this study were to elucidate the etiology, clinical presentation and outcomes associated with peritonitis in Lilongwe, Malawi. METHODS: All patients admitted to Kamuzu Central Hospital (KCH) who underwent an operation for treatment of peritonitis during the calendar year 2008 were eligible. Peritonitis was defined as abdominal rigidity, rebound tenderness, and/or guarding in one or more abdominal quadrants. Subjects were identified from a review of the medical records for all patients admitted to the adult general surgical ward and the operative log book. Those who met the definition of peritonitis and underwent celiotomy were included. RESULTS: 190 subjects were identified. The most common etiologies were appendicitis (22%), intestinal volvulus (17%), perforated peptic ulcer (11%) and small bowel perforation (11%). The overall mortality rate associated with peritonitis was 15%, with the highest mortality rates observed in solid organ rupture (35%), perforated peptic ulcer (33%), primary/idiopathic peritonitis (27%), tubo-ovarian abscess (20%) and small bowel perforation (15%). Factors associated with death included abdominal rigidity, generalized (versus localized) peritonitis, hypotension, tachycardia and anemia (p < 0.05). Age, gender, symptoms (obstipation, vomiting) and symptom duration, tachypnea, abnormal temperature, leukocytosis, hemoconcentration, thrombocytopenia and thrombocytosis were not associated with mortality (p = NS). CONCLUSIONS: There are several signs and laboratory findings predictive of poor outcome in Malawian patients with peritonitis. Tachycardia, hypotension, anemia, abdominal rigidity and generalized peritonitis are the most predictive of death (P < 0.05 for each). Similar to studies from other African countries, in our population the most common cause of peritonitis was appendicitis, and the overall mortality rate among all patients with peritonitis was 15%. Identified geographical differences included intestinal volvulus, rare in the US but the 2nd most common cause of peritonitis in Malawi and gallbladder disease, common in Ethiopia but not observed in Malawi. Future research should investigate whether correction of factors associated with mortality might improve outcomes. PMID- 22067900 TI - Individual variability and environmental characteristics influence older adults' abilities to manage everyday technology. AB - BACKGROUND: The ability to manage everyday technology (ET), such as computers and microwave ovens, is increasingly required in the performance of everyday activities and participation in society. This study aimed to identify aspects that influence the ability to manage ET among older adults with and without cognitive impairment. METHODS: Older adults with mild Alzheimer's disease and mild cognitive impairment and without known cognitive impairment were assessed as they managed their ET at home. Data were collected using the Management of Everyday Technology Assessment (META). Rasch-based measures of the person's ability to manage ET were analyzed. These measures were used as dependent variables in backward procedure ANOVA analyses. Different predefined aspects that could influence the ability to manage ET were used as independent variables. RESULTS: Three aspects had a significant effect upon the ability to manage ET. These were: (1) variability in intrapersonal capacities (such as "the capacity to pay attention and focus", (2) environmental characteristics (such as "the impact of the design") and (3) diagnostic group. CONCLUSIONS: Variability in intrapersonal capacities seems to be of more importance than the actual level of intrapersonal capacity in relation to the ability to manage ET for this sample. This implies that investigations of ability to manage ET should also include intraperson variability. Additionally, adaptations in environmental characteristics could simplify the management of ET to support older adults as technology users. PMID- 22067901 TI - Anti-inflammatory effects of benfotiamine are mediated through the regulation of the arachidonic acid pathway in macrophages. AB - Benfotiamine, a lipid-soluble analogue of vitamin B1, is a potent antioxidant that is used as a food supplement for the treatment of diabetic complications. Our recent study (U.C. Yadav et al., Free Radic. Biol. Med. 48:1423-1434, 2010) indicates a novel role for benfotiamine in the prevention of bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in murine macrophages. Nevertheless, it remains unclear how benfotiamine mediates anti inflammatory effects. In this study, we investigated the anti-inflammatory role of benfotiamine in regulating arachidonic acid (AA) pathway-generated inflammatory lipid mediators in RAW264.7 macrophages. Benfotiamine prevented the LPS-induced activation of cPLA2 and release of AA metabolites such as leukotrienes, prostaglandin E2, thromboxane 2 (TXB2), and prostacyclin (PGI2) in macrophages. Further, LPS-induced expression of AA-metabolizing enzymes such as COX-2, LOX-5, TXB synthase, and PGI2 synthase was significantly blocked by benfotiamine. Furthermore, benfotiamine prevented the LPS-induced phosphorylation of ERK1/2 and expression of transcription factors NF-kappaB and Egr-1. Benfotiamine also prevented the LPS-induced oxidative stress and protein-HNE adduct formation. Most importantly, compared to specific COX-2 and LOX-5 inhibitors, benfotiamine significantly prevented LPS-induced macrophage death and monocyte adhesion to endothelial cells. Thus, our studies indicate that the dual regulation of the COX and LOX pathways in AA metabolism could be a novel mechanism by which benfotiamine exhibits its potential anti-inflammatory response. PMID- 22067902 TI - Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo MUCT. AB - The effect of ibandronate 150 mg/once monthly in the treatment of post-menopausal osteopenia and osteoporosis on bone micro-structure at the distal tibia and radius has not been considered to date. Seventy post-menopausal women with osteoporosis or osteopenia were recruited. All subjects received calcium and vitamin D supplementation and were randomized to either a group which took 150 mg ibandronate oral monthly or a placebo group over a 12-month period. MUCT measures of the distal tibia and radius were conducted every three months, with DXA lumbar spine and hip measurements conducted only pre and post and serum markers of bone formation and resorption measured every 6 months. After 12-months no significant impact of ibandronate on the primary outcome measures bone-volume to tissue volume and trabecular separation at the distal tibia (p>=0.15) was found. Further multiple regression analyses of the primary end-points indicated a significant effect favoring the ibandronate intervention (p=0.045). Analysis of secondary end points showed greater increases in distal tibia cortical thickness, cortical density and total density (p<=0.043) with ibandronate and no significant effects at the distal radius, but greater increases of hip DXA-BMD and lumbar spine DXA BMD (p<=0.017). Ibandronate use resulted in a marked reduction in bone turnover (p<0.001). While ibandronate resulted in greater mineralization of bone, this effect differed from one body region to another. There was some impact of ibandronate on bone structure (cortical thickness) at the distal tibia, but not on bone-volume to tissue-volume or trabecular separation. PMID- 22067903 TI - Molecular characterisation of formalin-fixed paraffin-embedded (FFPE) breast tumour specimens using a custom 512-gene breast cancer bead array-based platform. AB - BACKGROUND: Formalin-fixed, paraffin-embedded (FFPE) tumour tissue represents an immense but mainly untapped resource with respect to molecular profiling. The DASL (cDNA-mediated Annealing, Selection, extension, and Ligation) assay is a recently described, RT-PCR-based, highly multiplexed high-throughput gene expression platform developed by Illumina specifically for fragmented RNA typically obtained from FFPE specimens, which enables expression profiling. In order to extend the utility of the DASL assay for breast cancer, we have custom designed and validated a 512-gene human breast cancer panel. METHODS: The RNA from FFPE breast tumour specimens were analysed using the DASL assay. Breast cancer subtype was defined from pathology immunohistochemical (IHC) staining. Differentially expressed genes between the IHC-defined subtypes were assessed by prediction analysis of microarrays (PAM) and then used in the analysis of two published data sets with clinical outcome data. RESULTS: Gene expression signatures on our custom breast cancer panel were very reproducible between replicates (average Pearson's R2=0.962) and the 152 genes common to both the standard cancer DASL panel (Illumina) and our breast cancer DASL panel were similarly expressed for samples run on both panels (average R2=0.877). Moreover, expression of ESR1, PGR and ERBB2 corresponded well with their respective pathology-defined IHC status. A 30-gene set indicative of IHC-defined breast cancer subtypes was found to segregate samples based on their subtype in our data sets and published data sets. Furthermore, several of these genes were significantly associated with overall survival (OS) and relapse-free survival (RFS) in these previously published data sets, indicating that they are biomarkers of the different breast cancer subtypes and the prognostic outcomes associated with these subtypes. CONCLUSION: We have demonstrated the ability to expression profile degraded RNA transcripts derived from FFPE tissues on the DASL platform. Importantly, we have identified a 30-biomarker gene set that can classify breast cancer into subtypes and have shown that a subset of these markers is prognostic of OS and RFS. PMID- 22067904 TI - Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology. AB - BACKGROUND: Mortality rates in lung cancer patients have not decreased significantly in recent years, even with the implementation of new therapeutic regimens. One of the main problems is that a large proportion of patients present local or distant metastasis at the time of diagnosis. The need for identification of novel biomarkers and therapeutic targets for a more effective management of lung cancer led us to investigate TMPRSS4, a protease reported to promote tumour growth and metastasis. MATERIAL AND METHODS: In all, 34 lung cancer cell lines were used to evaluate the TMPRSS4 expression. Cell migration and clonogenic assays, and an in-vivo lung metastasis model were used for functional analysis of the TMPRSS4 downregulation in H358, H441 and H2170 cell lines. The TMPRSS4 expression analysis in normal and malignant lung tissue samples was performed by qPCR. Five different microarray-based publicly available expression databases were used to validate our results and to study prognosis. RESULTS: The TMPRSS4 knock down in H358, H441 and H2170 cells resulted in a significant reduction in proliferation, clonogenic capacity and invasion. A significant (P<0.05) decrease in the lung colonisation and growth was found when mice were injected with TMPRSS4-depleated H358-derived clones, as compared with controls. Expression of TMPRSS4 showed a >30-fold increase (P<0.001) in tumours in comparison with non malignant samples. Levels in tumours with squamous cell carcinoma (SCC) histology were found to be significantly higher (P<0.001) than those with adenocarcinoma (AC) histology, which was confirmed in data retrieved from the microarrays. Kaplan-Meier curves demonstrated that high levels of TMPRSS4 were significantly associated (P=0.017) with reduced overall survival in the patients with SCC histology, whereas no correlation was found for the AC histology. CONCLUSION: Our results demonstrate that TMPRSS4 has a role in the lung cancer development. The potential use of TMPRSS4 as a biomarker for lung cancer detection or as a predictor of patient's outcome warrants further investigation. PMID- 22067905 TI - Tumor cell cross talk with tumor-associated leukocytes leads to induction of tumor exosomal fibronectin and promotes tumor progression. AB - Exosomes participate in intercellular communication, but most data published are based on exosomes released from in vitro cultured cells that do not communicate with neighboring cells located in the same microenvironment as the exosomal producing cells in vivo. In this study, our data show that co-culture of leukocytes isolated from breast tumor tissue leads to uptake of fibronectin (FN) on or in the tumor exosomes (Exo(fib+)). The induction of FN and exosomal uptake is tumor tissue derived and leukocyte specific, because leukocytes isolated from the peripheral blood of naive mice failed to induce FN uptake by tumor exosomes. Furthermore, depletion of both CD25(+) cells and Gr-1(+) cells from tumor associated leukocytes causes a reduction of Exo(fib+), suggesting that tumor associated CD25(+) cells and Gr-1(+) cells participate in FN production and uptake by tumor exosomes, resulting in Exo(fib+). As a result of tumor cells absorbing Exo(fib+), two major events are induced: focal adhesion kinase/Src dependent signaling pathways are activated, and the production of proinflammatory cytokines and metalloproteinase 9 is enhanced in response to absorbing exosomes. This, in turn, enhances tumor cell invasion in vitro and in vivo. Collectively, our findings provide evidence that exosomes released from freshly excised tumor tissue cells that have communicated/interacted with immune cells gain new immune evasion capacity. PMID- 22067906 TI - Persistent inflammation subverts thrombospondin-1-induced regulation of retinal angiogenesis and is driven by CCR2 ligation. AB - Neovascular retinal disease is a leading cause of blindness orchestrated by inflammatory responses. Although noninfectious uveoretinitis is mediated by CD4(+) T cells, in the persistent phase of disease, angiogenic responses are observed, along with degeneration of the retina. Full clinical manifestation relies on myeloid-derived cells, which are phenotypically distinct from, but potentially sharing common effector responses to age-related macular degeneration. To interrogate inflammation-mediated angiogenesis, we investigated experimental autoimmune uveoretinitis, an animal model for human uveitis. After the initial acute phase of severe inflammation, the retina sustains a persistent low-grade inflammation with tissue-infiltrating leukocytes for over 4 months. During this persistent phase, angiogenesis is observed as retinal neovascular membranes that arise from inflamed venules and postcapillary venules, increase in size as the disease progresses, and are associated with infiltrating arginase 1(+) macrophages. In the absence of thrombospondin-1, retinal neovascular membranes are markedly increased and are associated with arginase-1(-) CD68(+) macrophages, whereas deletion of the chemokine receptor CCR2 resulted in reduced retinal neovascular membranes in association with a predominant neutrophil infiltrate. CCR2 is important for macrophage recruitment to the retina in experimental autoimmune uveoretinitis and promotes chronicity in the form of a persistent angiogenesis response, which in turn is regulated by constitutive expression of angiogenic inhibitors like thrombospondin-1. This model offers a new platform to dissect the molecular and cellular pathology of inflammation induced ocular angiogenesis. PMID- 22067907 TI - Serine protease inhibition reduces post-ischemic granulocyte recruitment in mouse intestine. AB - Proteases and proteinase-activated receptor (PAR) activation are involved in several intestinal inflammatory conditions. We hypothesized that serine proteases and PAR activation could also modulate the intestinal injury induced by ischemia reperfusion (I-R). C57Bl/6 mice were subjected to 90 minutes of intestinal ischemia followed or not by reperfusion. Sham-operated animals served as controls. After ischemia, plasma and tissue serine protease activity levels were increased compared to the activity measured in plasma and tissues from sham operated mice. This increase was maintained or further enhanced after 2 and 5 hours of reperfusion, respectively. Trypsin (25 kDa) was detected in tissues both after ischemia and 2 hours of reperfusion. Treatment with FUT-175 (10 mg/kg), a potent serine protease inhibitor, increased survival after I-R, inhibited tissue protease activity, and significantly decreased intestinal myeloperoxidase (MPO) activity and chemokine and adhesion molecule expression. We investigated whether serine proteases modulate granulocyte recruitment by a PAR-dependent mechanism. MPO levels and adhesion molecule expression were significantly reduced in I-R groups pre-treated with the PAR(1) antagonist SCH-79797 (5 mg/kg) and in Par(2)( /-)mice, compared, respectively, to vehicle-treated group and wild-type littermates. Thus, increased proteolytic activity and PAR activation play a pathogenic role in intestinal I-R injury. Inhibition of PAR-activating serine proteases could be beneficial to reduce post-ischemic intestinal inflammation. PMID- 22067908 TI - Chronic inhibition of epidermal growth factor receptor tyrosine kinase and extracellular signal-regulated kinases 1 and 2 (ERK1/2) augments vascular response to limb ischemia in type 2 diabetic mice. AB - Type 2 diabetes is a key risk factor for ischemia-dependent pathology; therefore, a significant medical need exists to develop novel therapies that increase the formation of new vessels. We explored the therapeutic potential of epidermal growth factor receptor tyrosine kinase (EGFRtk) and extracellular signal regulated kinase 1/2 (ERK1/2) inhibition in impaired ischemia-induced neovascularization in type 2 diabetes. Unilateral femoral artery ligation was performed in diabetic (db(-)/db(-)) and their control (db(-)/db(+)) mice for 4 weeks, followed by treatments with EGFRtk and ERK1/2 inhibitors (AG1478, 10 mg/kg/day and U0126, 400 MUg/kg/day, respectively) for 3 weeks. Neovascularization, blood flow recovery, vascular and capillary density, and endothelial nitric oxide synthase activity were significantly impaired and were associated with enhanced EGFRtk and ERK1/2 activity in db(-)/db(-) mice. EGFRtk and ERK1/2 inhibitors did not have any effect in control mice, while in db(-)/db( ) mice there was a significant increase in neovascularization, blood flow recovery, vascular and capillary density, endothelial nitric oxide synthase activity, and were associated with a decrease in EGFRtk and ERK1/2 activity. Our data demonstrated that the inhibition of EGFRtk and ERK1/2 restored ischemia induced neovascularization and blood flow recovery in type 2 diabetic mice. Thus, EGFRtk and ERK1/2 could be possible targets to protect from ischemia-induced vascular pathology in type 2 diabetes. PMID- 22067909 TI - LPS-induced murine systemic inflammation is driven by parenchymal cell activation and exclusively predicted by early MCP-1 plasma levels. AB - Systemic inflammation remains a major cause of morbidity and mortality in the United States, across many disease processes. One classic murine model to study this syndrome is lipopolysaccharide (LPS)-induced Toll-like receptor 4 (TLR4) dependent systemic inflammation. Although most studies have focused on inflammatory cell TLR4 responses, parenchymal cells also express TLR4. Our objective was to define the in vivo role of parenchymal- versus marrow-derived cell activation via TLR4 during LPS-induced inflammation. Mice bearing TLR4 on parenchymal cells only, marrow-derived cells only, both, or neither were generated using bone marrow transplantation. Mortality occurred only in mice that had TLR4 expression on their parenchymal cells. Before onset, virtually all major plasma cytokines and blood neutrophil responses were related to marrow-derived cell activation via TLR4. The only cytokine predictive of oncoming systemic inflammation was the chemokine monocyte chemoattractant protein-1. Late blood neutrophil responses were related to the presence of TLR4 on either parenchymal or marrow cells, whereas plasma cytokine elevations late in LPS-induced systemic inflammation were dependent on mice having TLR4 in both cell compartments. Parenchymal cell activation via TLR4 is a key component of LPS-induced systemic inflammation and mortality, although most plasma cytokine levels and blood neutrophil responses were not key components. Given its unique role, future studies into monocyte chemoattractant protein-1's exact role during systemic inflammation are warranted. PMID- 22067910 TI - Cognitive decline typical of frontotemporal lobar degeneration in transgenic mice expressing the 25-kDa C-terminal fragment of TDP-43. AB - Transactive response DNA-binding protein 43 (TDP-43) is the pathological signature protein in several neurodegenerative disorders, including the majority of frontotemporal lobar degeneration cases (FTLD-TDP), motor neuron disease, and amyotrophic lateral sclerosis. Pathological TDP-43 is mislocalized from its nuclear location to the cytoplasm, where it accumulates and is proteolytically cleaved to form C-terminal fragments. Although the 25-kDa C-terminal fragment of TDP-43 (TDP-25) accumulates in affected brain regions, its role in the disease pathogenesis remains elusive. To address this problem, we have generated a novel transgenic mouse that selectively expresses TDP-25 in neurons. We show that transgenic mice expressing TDP-25 develop cognitive deficits associated with the build-up of soluble TDP-25. These cognitive deficits are independent of TDP-43 positive inclusions and occur without overt neurodegeneration. Additionally, we show that the expression of TDP-25 is sufficient to alter the processing of endogenous full-length TDP-43. These studies represent the first in vivo demonstration of a pathological role for TDP-25 and strongly suggest that the onset of cognitive deficits in TDP-43 proteinopathies is independent of TDP-43 inclusions. These data provide a framework for understanding the molecular mechanisms underlying the onset of cognitive deficits in FTLD-TDP and other TDP 43 proteinopathies; thus, the TDP-25 transgenic mice represent a unique tool to reach this goal. PMID- 22067911 TI - Chlamydia trachomatis disturbs epithelial tissue homeostasis in fallopian tubes via paracrine Wnt signaling. AB - The obligate intracellular pathogen Chlamydia trachomatis (Ctr) is a major cause of sexually transmitted disease and infertility worldwide. Ascending genital infections cause inflammation of fallopian tubes and subsequent scarring and occlusion. The cellular basis for such sequelae remains undetermined. We used confocal immunofluorescence microscopy to show that Ctr disrupts epithelial homeostasis in an ex vivo infection model of human fallopian tubes. Ctr triggered loss of polarity of inclusion harboring cells and of neighboring uninfected cells, as shown by subcellular redistribution of adhesion and polarity (occludin) markers. beta-catenin (a component of the adherens junction and a Wnt signaling transducer) was recruited to the bacterial inclusion, suggesting a role for Wnt signaling in Ctr-mediated tissue damage. Comparative microarray analysis of infected epithelium in the presence of the Wnt secretion inhibitor (IWP2) demonstrated that the transcriptional response to Ctr infection was highly dependent on active Wnt secretion, moreover IWP2 reversed Ctr-induced tissue phenotypes. Notably, we observed the up-regulation of differentiation and proliferation biomarkers olfactomedin 4 and epithelial cell adhesion molecule, and also Ctr-induced proteolytic activation of epithelial cell adhesion molecule. Thus, acute Ctr infection activates the paracrine Wnt signaling pathway, leading to profound disruption of epithelial structure and function that facilitates the dissemination of damage beyond that of infected cells. PMID- 22067912 TI - Apelin is required for non-neovascular remodeling in the retina. AB - Retinal pathologies are frequently accompanied by retinal vascular responses, including the formation of new vessels by angiogenesis (neovascularization). Pathological vascular changes may also include less well characterized traits of vascular remodeling that are non-neovascular, such as vessel pruning and the emergence of dilated and tortuous vessel phenotypes (telangiectasis). The molecular mechanisms underlying neovascular growth versus non-neovascular remodeling are poorly understood. We therefore undertook to identify novel regulators of non-neovascular remodeling in the retina by using the dystrophic Royal College of Surgeons (RCS) rat and the retinal dystrophy 1 (RD1) mouse, both of which display pronounced non-neovascular remodeling. Gene expression profiling of isolated retinal vessels from these mutant rodent models and wild-type controls revealed 60 differentially expressed genes. These included the genes for apelin (Apln) and for its receptor (Aplnr), both of which were strongly up regulated in the mutants. Crossing RD1 mice into an Apln-null background substantially reduced vascular telangiectasia. In contrast, Apln gene deletion had no effect in two models of neovascular pathology [laser-induced choroidal neovascularization and the very low density lipoprotein receptor (Vldlr)-knockout mouse]. These findings suggest that in these models apelin has minimal effect on sprouting retinal angiogenesis, but contributes significantly to pathogenic non neovascular remodeling. PMID- 22067913 TI - A collagen alpha2(I) mutation impairs healing after experimental myocardial infarction. AB - Collagen breakdown and de novo synthesis are important processes during early wound healing after myocardial infarction (MI). We tested the hypothesis that collagen I, the main constituent of the extracellular matrix, affects wound healing after MI. The osteogenesis imperfecta mouse (OIM), lacking procollagen alpha2(I) expression, represents a model of the type III form of the disease in humans. Homozygous (OIM/OIM), heterozygous (OIM/WT), and wild-type (WT/WT) mice were subjected to a permanent myocardial infarction protocol or sham surgery. Baseline functional and geometrical parameters determined by echocardiography did not differ between genotypes. After MI but not after sham surgery, OIM/OIM animals exhibited significantly increased mortality, due to early ventricular rupture between day 3 and 7. Echocardiography at day 1 demonstrated increased left ventricular dilation in OIM/OIM animals. Less collagen I mRNA within the infarct area was found in OIM/OIM animals. At 2 days after MI, MMP-9 expression in the infarct border zone was higher in OIM/OIM than in WT/WT animals. Increased granulocyte infiltration into the infarct border zone occurred in OIM/OIM animals. Neither granulocyte depletion nor MMP inhibition reduced mortality in OIM/OIM animals. In this murine model, deficiency of collagen I leads to a myocardial wound-healing defect. Both structural alterations within pre-existing collagen matrix and impaired collagen de novo expression contribute to a high rate of early myocardial rupture after MI. PMID- 22067914 TI - CCR7 with S1P1 signaling through AP-1 for migration of Foxp3+ regulatory T-cells controls autoimmune exocrinopathy. AB - Forkhead box p3-positive (Foxp3(+)) regulatory T cells (T(reg) cells) participate in maintaining peripheral immune tolerance and suppressing autoimmunity. We recently reported that in situ patrolling by C-C-chemokine receptor 7 (CCR7)(+) T(reg) cells in target organs is essential for controlling autoimmune lesions in Sjogren's syndrome. In the present study, the molecular mechanism underlying CCR7 mediated T(reg) cell migration was investigated in a mouse model. The impaired migratory response of Ccr7(-/-) T(reg) cells to sphingosine 1-phosphate (S1P) occurred because of defective association of S1P receptor 1 (S1P(1)) with a G coupled-protein. In addition, T-cell receptor (TCR)- and S1P(1)-mediated Ras related C3 botulinum toxin substrate 1 (Rac-1), extracellular signal-related kinase (ERK), and c-Jun phosphorylation required for activator protein 1 (AP-1) transcriptional activity were significantly impaired in Ccr7(-/-) T(reg) cells. Surprisingly, the abnormal nuclear localization of Foxp3 was detected after abrogation of the c-Jun and Foxp3 interaction in the nucleus of Ccr7(-/-) T(reg) cells. These results indicate that CCR7 essentially controls the migratory function of T(reg) cells through S1P(1)-mediated AP-1 signaling, which is regulated through its interaction with Foxp3 in the nucleus. PMID- 22067915 TI - 'Oh dear, should I really be saying that on here?': issues of identity and authority in an online diabetes community. AB - We explore peer-to-peer discussions which took place in a UK-based diabetes 'Virtual Clinic' online community. In particular, we seek to understand the rhetorical nature and content of exchanges over a period of six months from the community's inception. Data were captured weekly and analysis based on thematic discourse analysis. Two key issues emerged regarding how the community shaped the nature of the discussion forum. First, the identity of the forum was established, and boundaries drawn about what was, and was not, acceptable. Second, participants sought to present themselves as reliable and authoritative sources of information. Internet discussion communities are shaped in important ways early on by the community of users, including how the character and focus of discussion is formed, and how both information and users can be constructed as authoritative and reliable. PMID- 22067916 TI - Gendered perceptions of own and partner weight-level. AB - This study investigates gender differences in perceptions of body weight. Previous research has found significant gender differences in perceived weight level, but less is known about weight perceptions of the opposite gender. Based on Danish survey data (859 women and 160 men), the discrepancy between BMI weight level and self-perceived weight-level is estimated as well as the perception of one's partner's weight-level. Two main empirical conclusions emerge. First, there are significant gender differences in weight assessment. Whereas women assess weight according to the standardized BMI weight-levels for both genders, men assess weight according to gender. The weight-level of men is often underestimated by men themselves, but both men and women tend to overestimate the weight-level of women in the lower BMI deciles compared to standardized BMI weight-levels. Second, there is greater underestimation of weight-levels for individuals in the higher BMI--especially regarding weight perceptions of the opposite gender. These findings are discussed within a framework of socio cultural theory of body image and gendered relations. PMID- 22067917 TI - Compton scattering artifacts in electron excited X-ray spectra measured with a silicon drift detector. AB - Artifacts are the nemesis of trace element analysis in electron-excited energy dispersive X-ray spectrometry. Peaks that result from nonideal behavior in the detector or sample can fool even an experienced microanalyst into believing that they have trace amounts of an element that is not present. Many artifacts, such as the Si escape peak, absorption edges, and coincidence peaks, can be traced to the detector. Others, such as secondary fluorescence peaks and scatter peaks, can be traced to the sample. We have identified a new sample-dependent artifact that we attribute to Compton scattering of energetic X-rays generated in a small feature and subsequently scattered from a low atomic number matrix. It seems likely that this artifact has not previously been reported because it only occurs under specific conditions and represents a relatively small signal. However, with the advent of silicon drift detectors and their utility for trace element analysis, we anticipate that more people will observe it and possibly misidentify it. Though small, the artifact is not inconsequential. Under some conditions, it is possible to mistakenly identify the Compton scatter artifact as approximately 1% of an element that is not present. PMID- 22067918 TI - Deliberations and recommendations of the Pediatric Emergency Mass Critical Care Task Force: executive summary. PMID- 22067919 TI - Treatment and triage recommendations for pediatric emergency mass critical care. AB - INTRODUCTION: This paper will outline the Task Force recommendations regarding treatment during pediatric emergency mass critical care, issues related to the allocation of scarce resources, and current challenges in the development of pediatric triage guidelines. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subcommittees by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines through consensus-based study of the literature and convened October 6-7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: Recommendations are divided into three operational sections. The first section provides pediatric emergency mass critical care recommendations for hospitals that normally provide care to pediatric patients. The second section provides recommendations for pediatric emergency mass critical care at hospitals that do not routinely provide care to pediatric patients. The final section provides a discussion of issues related to developing triage algorithms and protocols and the allocation of scarce resources during pediatric emergency mass critical care. PMID- 22067920 TI - Supplies and equipment for pediatric emergency mass critical care. AB - INTRODUCTION: Epidemics of acute respiratory disease, such as severe acute respiratory syndrome in 2003, and natural disasters, such as Hurricane Katrina in 2005, have prompted planning in hospitals that offer adult critical care to increase their capacity and equipment inventory for responding to a major demand surge. However, planning at a national, state, or local level to address the particular medical resource needs of children for mass critical care has yet to occur in any coordinated way. This paper presents the consensus opinion of the Task Force regarding supplies and equipment that would be required during a pediatric mass critical care crisis. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subcommittees by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines through consensus-based study of the literature and convened October 6-7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: The Task Force endorsed the view that supplies and equipment must be available for a tripling of capacity above the usual peak pediatric intensive care unit capacity for at least 10 days. The recommended size-specific pediatric mass critical care equipment stockpile for two types of patients is presented in terms of equipment needs per ten mass critical care beds, which would serve 26 patients over a 10-day period. Specific recommendations are made regarding ventilator capacity, including the potential use of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation. Other recommendations include inventories for disposable medical equipment, medications, and staffing levels. PMID- 22067921 TI - Neonatal and pediatric regionalized systems in pediatric emergency mass critical care. AB - INTRODUCTION: Improved health outcomes are associated with neonatal and pediatric critical care in well-organized, cohesive, regionalized systems that are prepared to support and rehabilitate critically ill victims of a mass casualty event. However, present systems lack adequate surge capacity for neonatal and pediatric mass critical care. In this document, we outline the present reality and suggest alternative approaches. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subcommittees by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines through consensus-based study of the literature and convened October 6-7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: States and regions (facilitated by federal partners) should review current emergency operations and devise appropriate plans to address the population-based needs of infants and children in large-scale disasters. Action at the state, regional, and federal levels should address legal, operational, and information systems to provide effective pediatric mass critical care through: 1) predisaster/mass casualty planning, management, and assessment with input from child health professionals; 2) close cooperation, agreements, public-private partnerships, and unique delivery systems; and 3) use of existing public health data to assess pediatric populations at risk and to model graded response plans based on increasing patient volume and acuity. PMID- 22067922 TI - Education in a pediatric emergency mass critical care setting. AB - INTRODUCTION: An emergency mass critical care event puts significant strains on all healthcare resources, including equipment, supplies, and manpower; it leads to extraordinary stresses on healthcare providers, many of whom will be expected to deliver care outside of their usual scope of practice. Education and educational resources will be critically important for training providers and diminishing the stress, anxiety, and chaos of delivering pediatric emergency mass critical care. This article suggests educational tools, as well as potential resources, that need to be developed to cope with a pediatric emergency mass critical care event. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subgroups by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines through consensus-based study of the literature and convened October 6-7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: Identifying educational needs to prepare for a pediatric emergency mass critical care event is essential for all healthcare organizations. Educational strategies and tactics should be developed at multiple levels for a comprehensive approach to preparing for pediatric emergency mass critical care. PMID- 22067923 TI - Pediatric emergency mass critical care: the role of community preparedness in conserving critical care resources. AB - INTRODUCTION: Public health emergencies require resources at state, regional, federal, and often international levels; however, community preparedness is the crucial first step in managing these events and mitigating their consequences, particularly for children. Community preparedness can be optimized through system wide planning that includes integrating multiple points of contact, such as the community, prehospital care, health facilities, and regional level of care assets.Citizen readiness, call centers, alternate care facilities, emergency medical services, and health emergency operations centers linked to community incident command systems should be considered as important options for delivery of population-based care. Early collaboration between pediatric clinicians and public health authorities is essential to ensure that pediatric needs are addressed in community preparedness for mass critical care events. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subcommittees by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines and convened October 6-7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: The Pediatric Emergency Mass Critical Care Task Force recommends active promotion of programs to ensure an informed citizenry; education of children and families in Centers for Disease Control and Prevention community mitigation strategies; emphasis on community-level preparedness empowering the public to provide self care; use of 9-1-1 telephone triage with pre-established protocols and in coordination with emergency medical services; and advocacy for healthcare coalitions and other creative operational concepts that provide guidance and protocols for care of the pediatric population. PMID- 22067924 TI - Legal considerations during pediatric emergency mass critical care events. AB - INTRODUCTION: Recent public health emergencies, such as the 2009 Influenza A/H1N1 Pandemic and Hurricane Katrina, underscore the importance of developing healthcare response plans and protocols for disasters impacting large populations. Significant research and scholarship, including the 2009 Institute of Medicine report on crisis standards of care and the 2008 Task Force for Mass Critical Care recommendations, provide guidance for healthcare responses to catastrophic emergencies. Most of these efforts recognize but do not focus on the unique needs of pediatric populations. In 2008, the Centers for Disease Control and Prevention supported the formation of a task force to address pediatric emergency mass critical care response issues, including legal issues. Liability is a significant concern for healthcare practitioners and facilities during pediatric emergency mass critical care that necessitates a shift to crisis standards of care. This article describes the legal considerations inherent in planning for and responding to catastrophic health emergencies and makes recommendations for pediatric emergency mass critical care legal preparedness. METHODS: The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010, to review the pediatric emergency mass critical care recommendations developed by a 17-member steering committee. During the meeting, experts determined that the recommendations would be strengthened by a manuscript addressing legal issues. Authors drafted the manuscript through consensus-based study of peer-reviewed research, literature reviews, and expert opinion. The manuscript was reviewed by Pediatric Emergency Mass Critical Care Steering Committee members and additional legal counsel and revised. TASK FORCE RECOMMENDATIONS: While the legal issues associated with providing pediatric emergency mass critical care are not unique within the overall context of disaster healthcare, the scope of the parens patriae power of states, informed consent principles, and security should be considered in pediatric emergency mass critical care planning and response efforts because parents and legal guardians may be unavailable to participate in healthcare decision making during disasters. In addition, practitioners who follow properly vetted and accepted pediatric emergency mass critical care disaster protocols in good faith should be protected from civil liability, and healthcare facilities that provide pediatric care should incorporate informed consent and security protocols into their disaster plans. PMID- 22067925 TI - Pediatric emergency mass critical care: focus on family-centered care. AB - INTRODUCTION: Pediatric emergency mass critical care during disasters requires modifications to standard healthcare operations. Modification of standards for pediatric emergency mass critical care should include incorporation of family centered care principles. Family-centered care, which is an integral aspect of current pediatric practice, encourages active participation of the child's family in medical care delivery. While family-centered care should be practical in most disasters, whether we can operationalize it in pediatric emergency mass critical care is unknown. However, every effort to adhere to the principles should be made. This manuscript addresses some of the basic tensions that exist between creating efficient disaster-related standards and offering family-centered care by augmenting the concepts outlined elsewhere in the supplement with practical suggestions on incorporating family-centered care. In addition, this manuscript demonstrates how family-centered care benefits not only children and families, but also the staff providing care to pediatric patients in disasters. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subgroups by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines through consensus-based study of the literature and convened October 6-7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: This paper offers a list of practical suggestions for incorporating family-centered care principles into each of the following healthcare settings during a disaster, including a pediatric emergency mass critical care event: emergency medical services transport, emergency departments, pediatric intensive care units, general pediatric wards, and alternative sites. Disaster and pediatric emergency mass critical care responses must incorporate family-centered care principles to the extent possible in a variety of healthcare settings. PMID- 22067926 TI - Ethical issues in pediatric emergency mass critical care. AB - INTRODUCTION: As a result of recent events, including natural disasters and pandemics, mass critical care planning has become a priority. In general, planning involves limiting the scope of disasters, increasing the supply of medical resources, and allocating scarce resources. Entities at varying levels have articulated ethical frameworks to inform policy development. In spite of this increased focus, children have received limited attention. Children require special attention because of their unique vulnerabilities and needs. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subgroups by topic area and performed literature reviews of MEDLINE and Ovid databases. Draft documents were subsequently developed and revised based on the feedback from the Task Force. The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. This document reflects expert input from the Task Force in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: The Ethics Subcommittee recommends that surge planning seek to provide resources for children in proportion to their percentage of the population or preferably, if data are available, the percentage of those affected by the disaster. Generally, scarce resources should be allocated on the basis of need, benefit, and the conservation of resources. Estimates of need, benefit, and resource utilization may be more subjective or objective. While the Subcommittee favors more objective methods, pediatrics lacks a simple, validated scoring system to predict benefit or resource utilization. The Subcommittee hesitantly recommends relying on expert opinion while pediatric triage tools are developed. If resources remain inadequate, they should then be allocated based on queuing or lottery. Choosing between these methods is based on ethical, psychological, and practical considerations upon which the Subcommittee could not reach consensus. The Subcommittee unanimously believes the proposal to favor individuals between 15 and 40 yrs of age is inappropriate. Other age-based criteria and criteria based on social role remain controversial. The Subcommittee recommends continued work to engage all stakeholders, especially the public, in deliberation about these issues. PMID- 22067927 TI - The reality of pediatric emergency mass critical care in the developing world. AB - INTRODUCTION: Public health emergencies resulting from major man-made crises and large-scale natural disasters severely impact developing countries, causing unprecedented rates of indirect mortality and morbidity, especially in children and women. Concomitantly, the state of children's health in the least-developed countries is the worst since the 1950s before the Declaration of Alma Ata. Worldwide decline in public health protections, infrastructures, and systems, and a health worker crisis primarily in Africa and Asia, limit the delivery of intensive and critical care services. METHODS: In May 2008, the Task Force for Mass Critical Care published guidance on provision of mass critical care to adults. Acknowledging that the critical care needs of children during disasters were unaddressed by this effort, a 17-member Steering Committee, assembled by the Oak Ridge Institute for Science and Education with guidance from members of the American Academy of Pediatrics, convened in April 2009 to determine priority topic areas for pediatric emergency mass critical care recommendations.Steering Committee members established subgroups by topic area and performed literature reviews of MEDLINE and Ovid databases. The Steering Committee produced draft outlines through consensus-based study of the literature and convened October 6 7, 2009, in New York, NY, to review and revise each outline. Eight draft documents were subsequently developed from the revised outlines as well as through searches of MEDLINE updated through March 2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was compiled and the Steering Committee revised each document to reflect expert input in addition to the most current medical literature. TASK FORCE RECOMMENDATIONS: Using pandemics as a model of public health emergencies, steps to improve care to the most vulnerable of populations are outlined, including mandates under the International Health Regulations Treaty of 2007 and World Health Organization guidelines. Recommendations include an emphasis on first improving primary care, prevention, and basic emergency care, where possible. Advances in care should move incrementally without compromising primary care resources. A first step in preparing for a pandemic in developing countries involves building capacity in public health surveillance and proven community containment and mitigation strategies. Given the severe lack of healthcare workers in at least 57 countries, the Task Force also supports World Health Organization's recommendations that planning for a public health emergency include means for health workers to collaborate with staff in the military, transport, and education sectors as well as international healthcare workers to maximize the efficiency of scarce human resources. Rapid response teams can be augmented by international subject matter experts if these do not exist at the country level. PMID- 22067928 TI - Venous anomalies and horseshoe kidney. A minefield in open vascular surgery. PMID- 22067929 TI - Chronic inflammation links cardiovascular, metabolic and renal diseases. AB - Chronic inflammation appears to underlie most, if not all, the chronic diseases of today, including cardiovascular disease, type 2 diabetes, chronic kidney disease, Alzheimer's disease and cancer. We have demonstrated that obesity induces chronic local inflammation in adipose tissue. We also found that chronic inflammation is crucially involved in the development of heart failure and chronic kidney disease. In this article, I review recent findings reported by my group and others regarding the mechanisms underlying the chronic inflammatory processes commonly observed in adipose tissue, heart and kidney. I then discuss the key features of the chronic inflammation seen in chronic diseases. PMID- 22067930 TI - Urgent statement on antithrombotic therapy of atrial fibrillation. PMID- 22067931 TI - French national wound management survey: choice criteria of dressings. AB - Across Europe, wound care management is organized differently, and in some countries such as the UK or Denmark, wound healing centres have been implemented. In France, a large number of health professionals are not sufficiently educated in wound care management during their vocational training. The rapid evolution of dressings has changed wound management practices and has given rise to new professional recommendations. This national survey was carried out in France in 2009, including 465 health professionals, to determine the criteria they use to choose a dressing and their habits of care with acute or chronic wounds. Around 73% of respondents were nurses and, on average, participants took care of 43 wounds per month. It was also found that 89% of the health professionals who took part prefer the sequential treatment of the wound based on its appearance. Regardless of whether the wound is acute or chronic, the priorities for wound care and the choice of dressing are the management of the exudate and the prevention or treatment of infection. These results put into evidence the adequacy of the recommendations by these practitioners and the good correlation between the choice of dressing and the local therapeutic goal. To reach the same level of expertise, the professional training for health professionals who are less frequently involved in wound care is necessary. PMID- 22067932 TI - A meta-synthesis of research on leg ulceration and neuropathic pain component and sequelae. AB - Leg ulceration represents a substantial health problem, and pain is likely to be an associated symptom. The aim of this meta-synthesis was to undertake a systematic review of qualitative studies investigating the experience of chronic painful leg ulceration. This study undertook the meta-synthesis approach described by Sandelowski and Barroso (2003), which is a synthesis and re interpretation of the findings from several qualitative studies. Findings were extracted and synthesized. The overarching theme was that patients with chronic leg ulceration suffer from persistent pain with associated sequelae. Word descriptors used by participants also suggested that patients have neuropathic pain. In addition, findings from the meta-synthesis suggested that pain associated with chronic leg ulcer may have a neuropathic pain component. Pain associated with leg ulceration is likely to have nociceptive properties as well as neuropathic properties. If neuropathic pain is not identified and managed effectively, patients are at risk of developing a chronic pain condition with associated sequelae, such as poor sleep, depression and suicidal ideation. It is proposed that early identification and management may enable appropriate pain management which may prevent or reduce the associated risks. PMID- 22067933 TI - Laboratory performance of alternating pressure air mattresses component and sequelae. AB - The performance of three different alternating pressure air mattresses with different geometries of air cell were compared (Nimbus 3, Heritage, Tamora Plus), using simple performance indices based on pressure mapping. The aim of this study was to examine the effect on performance of elevating the backrest and thigh section of the bed into sitting position. Ten healthy volunteers of various sizes were pressure-mapped over the full pressure cycle on three alternating pressure air mattresseses with differing cell geometries. This was then repeated with the beds profiled to a sitting position. Performance of the alternating pressure air mattresses in terms of their ability to redistribute pressure dynamically was assessed in the different positions. The different alternating pressure air mattresses performed similarly with the bed in the lying flat position, but smaller cells appeared to be more effective in the sitting position. A conclusion was made that cell geometry may have an effect on the ability of the mattress to achieve alternating behaviour in the sitting position. PMID- 22067934 TI - Clinical evaluation of Allevyn Gentle Border LiteTM within one health trust. AB - This article outlines the financial cost of wound care and the importance of appropriate dressings to achieve both clinical and economic outcomes. A clinical evaluation of Allevyn Gentle Border LiteTM including 50 patients within one health trust was undertaken to assess ease of application, wear time, ease of removal, durability and patient comfort. An observation is made that wound care is complex and health professionals require a knowledge and understanding of the wound healing process, pain, dressing products, asepsis, microbiology, pharmacology, psychosocial factors, and ethics, and should possess good communication skills. A conclusion is made that the 50 patient evaluation demonstrates the flexibility of the Allevyn Gentle Border Lite, which allows for a secure fit, provides active fluid management in its control of exudates, may be applied to patients with fragile skin, thereby avoiding the need for secondary retention, and may be used on difficult-to-dress areas. PMID- 22067935 TI - When is a grade 4 pressure ulcer not grade 4? AB - The adoption of the European Pressure Ulcer Advisory Panel (EPUAP) (2009) pressure ulcer classification system within healthcare trusts in the UK has provided health professionals with a common approach for the description of tissue damage for pressure ulcers. However, the omission of the 'unstageable/unclassified' and 'suspected deep tissue injury under intact skin' has caused difficulties when the visual appearance of pressure ulcers falls outside the four grades listed in the classification system. These difficulties lead health professionals to overestimate the degree of tissue damage, resulting in confusion in regards to determining the true extent of the tissue damage and often misdirection of scarce resources (Moore, 2005). The Berkshire Tissue Viability Nurses Group attempted to bring clarity to the situation by highlighting the issues to raise awareness and stimulate discussion among health professionals. The author, with support of the Berkshire Tissue Viability Nurses Group, first presented the content of this article at a meeting of the No Needless Skin Breakdown Work Stream meeting of the South Central Strategic Health Authority Patient Safety Federation in January 2011. PMID- 22067936 TI - Fusobacterium nucleatum: an emerging gut pathogen? AB - The Gram-negative, non-sporulating, obligately anaerobic species, Fusobacterium nucleatum, is rapidly gaining notoriety as a pathogen with a surprising number of associated diseases. Recently, we have found that F. nucleatum is a more common resident of the GI tract than originally thought, and thus, through several studies, we have attempted to determine its gut-relevant potential for virulence. We have found that F. nucleatum possesses a number of pathogenic traits with relevance to gut diseases such as inflammatory bowel disease (IBD), however, we have also documented strain-associated differences in virulence. An intriguing picture emerges that paints F. nucleatum as both conferring beneficial as well as detrimental effects on host cells; and we suggest that the ultimate effects of F. nucleatum infection in the gut are a consequence of the microbes with which this species aggregates. PMID- 22067937 TI - N-Glycans on secretory component: mediators of the interaction between secretory IgA and gram-positive commensals sustaining intestinal homeostasis. AB - Human beings live in symbiosis with billions of microorganisms colonizing mucosal surfaces. The understanding of the mechanisms underlying this fine-tuned intestinal balance has made significant processes during the last decades. We have recently demonstrated that the interaction of SIgA with Gram-positive bacteria is essentially based on Fab-independent, glycan-mediated recognition. Results obtained using mouse hybridoma- and colostrum-derived secretory IgA (SIgA) consistently show that N-glycans present on secretory component (SC) play a crucial role in the process. Natural coating may involve specific Gram-positive cell wall components, which may explain selective recognition at the molecular level. More widely, the existence of these complexes is involved in the modulation of intestinal epithelial cell (IEC) responses in vitro and the formation of intestinal biofilms. Thus, SIgA may act as one of the pillars in homeostatic maintenance of the microbiota in the gut, adding yet another facet to its multiple roles in the mucosal environment. PMID- 22067938 TI - Polyethylene glycol diminishes pathological effects of Citrobacter rodentium infection by blocking bacterial attachment to the colonic epithelia. AB - Infections from enteric bacteria such as enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC) are a public health threat worldwide. EPEC and EHEC are extracellular pathogens, and their interaction with host surface receptors is critical to the infection process. We previously demonstrated that polyethylene glycol (PEG) downregulates surface receptors in intestinal cells. Here we show that PEG decreases beta1-integrin, the surface receptor in intestinal cells that is critical for EPEC and EHEC attachment. We hypothesized that PEG would inhibit the attachment of these enteric pathogens to host cells and improve clinical signs of infection. We found that attachment of the mouse enteric pathogen Citrobacter rodentium, which belongs to the same group of pathogens as EPEC and EHEC, was attenuated by the concurrent presence of PEG. Pretreatment with PEG, without concurrent presence during infection, also reduced bacterial attachment. This finding was further supported in vivo such as that PEG administered by gavage daily during infection as well as prior to infection significantly decreased C. rodentium in the colon and improved the appearance of the infected colon in mice. In addition, PEG decreased the beta1-integrin in colonic mucosa and reduced the C. rodentium-induced activation of epidermal growth factor receptors. PEG also significantly reduced infection-induced colonic inflammation. Finally, PEG efficiently reduced C. rodentium shedding from the colon during infection. In conclusion, PEG can be an efficient and safe preventive agent against EPEC and EHEC infections. PMID- 22067939 TI - Beneficial effect of probiotics in IBD: are peptidogycan and NOD2 the molecular key effectors? AB - Although the beneficial capacities of probiotics are more and more substantiated, their effects clearly depend on the strains used and their mechanisms of action remain poorly understood. Recent evidences have highlighted the potential role of cell-wall components in the anti-inflammatory capacity of selected lactobacilli. In this addendum, we summarize our recent results concerning the role of peptidoglycan (PGN) and NOD2 signaling in the regulation of intestinal inflammation. We showed that the protective effect of Lactobacillus PGN is strain specific and linked to the induction of diverse immune regulatory pathways. Moreover the beneficial effect of Lactobacillus PGN correlated with the release of a specific muropeptide sensed by NOD2. These findings allow for a better understanding of how probiotic lactobacilli exert their beneficial effect and will help guide for more successful strain selection. PMID- 22067940 TI - A role for quorum sensing in regulating innate immune responses mediated by Vibrio cholerae outer membrane vesicles (OMVs). AB - Outer membrane vesicles (OMVs) are released from many Gram-negative bacteria. OMVs interact with and are taken up by human cells. We and others have now showed that OMVs contain peptidoglycan, which is sensed mainly by the pattern recognition receptor NOD1 in the cytoplasm of host cells. Vibrio cholerae is clinically important as one of the causative agents of severe dehydrating diarrhea in humans. We showed that non-O1 non-O139 V. cholerae (NOVC) strains of V. cholera produce OMVs. Of note, we revealed that NOVC can evade NOD1-mediated immune surveillance by the quorum sensing machinery. Here we review these recent findings and discuss the relevance for our understanding of bacterial infections and innate immune responses. PMID- 22067941 TI - The design of probiotic studies to substantiate health claims. AB - The EC Regulation No. 1924/2006 on Nutrition and Health claims made on foods has generated considerable debate and concern among scientists and industry. At the time of writing, the European Food Safety Authority (EFSA) has not approved any probiotic claims despite numerous human trials and meta-analyses showing evidence of beneficial effects. On 29th and 30th September 2010, ten independent, academic scientists with a documented record in probiotic research, met to discuss designs for future probiotic studies to demonstrate health benefits for gut and immune function. The expert panel recommended the following: (i) always formulate a precise and concrete hypothesis, and appropriate goals and parameters before starting a trial; (ii) ensure trials have sufficient sample size, such that they are adequately powered to reach statistically significant conclusions, either supporting or rejecting the a priori hypothesis, taking into account adjustment for multiple testing (this might necessitate more than one recruitment site); (iii) ensure trials are of appropriate duration; (iv) focus on a single, primary objective and only evaluate multiple parameters when they are hypothesis-driven. The panel agreed that there was an urgent need to better define which biomarkers are considered valuable for substantiation of a health claim. As a first step, the panel welcomed the publication on the day of the meeting of EFSA's draft guidance document on immune and gut health, although it came too late for study designs and dossiers to be adjusted accordingly. New validated biomarkers need to be identified in order to properly determine the range of physiological functions influenced by probiotics. In addition, validated biomarkers reflecting risk factors for disease, are required for article 14 claims (EC Regulation No. 1924/2006). Finally, the panel concluded that consensus among scientists is needed to decide appropriate clinical endpoints for trials. PMID- 22067942 TI - Rud syndrome does not exist. PMID- 22067943 TI - Maternal intake of fatty acids during pregnancy and allergies in the offspring. AB - Fatty acids (FA) are known to have a number of immunological effects and, accordingly, may play a role in the development of allergic diseases. We investigated the effect of maternal intake of FA during pregnancy on the risk of allergic rhinitis, wheeze and atopic eczema in children aged 5 years. The present study analysed data from the Finnish Type 1 Diabetes Prediction and Prevention Nutrition Study, a population-based birth cohort study with a 5-year follow-up. Complete information on maternal diet (assessed by a validated FFQ) and International Study of Asthma and Allergies in Childhood-based allergic outcomes was available for 2441 children. Cox proportional regression and logistic regression were used for the analyses. After adjusting for potential confounding variables, high maternal consumption of butter and butter spreads (hazard ratio (HR) 1.33; 95 % CI 1.03, 1.71) and higher ratio of n-6:n-3 FA (HR 1.37; 95 % CI 1.07, 1.77) during pregnancy were associated with an increased risk of allergic rhinitis in the offspring by 5 years of age. High maternal intakes of total PUFA (HR 0.71; 95 % CI 0.52, 0.96) and alpha-linolenic FA (HR 0.73; 95 % CI 0.54, 0.98) were associated with a decreased risk of allergic rhinitis. However, these results lost their significance after adjustment for multiple comparisons. Overall, our data suggest that maternal consumption of butter, the ratio of n-6:n 3 FA and intake of PUFA and alpha-linolenic FA during pregnancy may be potential determinants of allergic rhinitis in the offspring. PMID- 22067944 TI - RAGE does not contribute to renal injury and damage upon ischemia/reperfusion induced injury. AB - The receptor for advanced glycation end products (RAGE) mediates a variety of inflammatory responses in renal diseases, but its role in renal ischemia/reperfusion (I/R) injury is unknown. We showed that during renal I/R, RAGE ligands HMGB1 and S100B are expressed. However, RAGE deficiency does not affect renal injury and function upon I/R-induced injury. PMID- 22067946 TI - Current world literature. PMID- 22067949 TI - Eczema diagnosis and management in the community. AB - The old saying, 'a stitch in time saves nine' is particularly true in the management of eczema. Early diagnosis and the recognition of an underlying cause can mean that more simple measures, such as moisturizers, may be sufficient to keep eczema under control, while the identification of an allergic stimulus can forestall further problems. Equally, being aware of what action to take when a course of treatment is ineffective, and having the ability to teach parents and families to realize when they need extra help, may allow changes to be made that will restore control of the condition more quickly. An understanding and empathetic ear may make all the difference when a patient is having to come to terms with eczema. This article discusses the aetiology and symptoms of different types of eczema, and summarises the range of available options for the management of this often disruptive condition. PMID- 22067945 TI - Polyphenolic extract of lotus root (edible rhizome of Nelumbo nucifera) alleviates hepatic steatosis in obese diabetic db/db mice. AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease of industrialized countries. Thus, discovering food components that can ameliorate NAFLD is of interest. Lotus root, the edible rhizome of Nelumbo nucifera, contains high levels of polyphenolic compounds, and several health-promoting properties of lotus root have been reported. In this study, we tested whether feeding a polyphenolic extract of lotus root to db/db mice protects them from hepatic steatosis. RESULTS: After 3 weeks of feeding, the hepatomegaly and hepatic triglyceride accumulation were markedly alleviated in the lotus polyphenol-diet-fed db/db mice relative to the control mice. Although the lipolytic enzyme activity was not changed, the activities of lipogenic enzymes, such as fatty acid synthase and malic enzyme, were significantly lower in the lotus polyphenol diet-fed db/db mice. Additionally, the ESI-IT/MS and MALDI-TOF MS spectra revealed the presence of B-type proanthocyanidin polymers with polymerization degree up to 9 in the polyphenolic lotus root extract. CONCLUSION: We speculate that the condensed tannins contained in lotus root can alleviate hepatic steatosis by suppressing the lipogenic enzyme activity in the livers of db/db mice. PMID- 22067950 TI - Advance care planning: thinking ahead to achieve our patients' goals. AB - The End of Life Care Strategy for England describes advance care planning (ACP) as a 'voluntary process of discussion about future care...concerns and wishes...values or personal goals for care, their understanding of their illness and prognosis...wishes for types of care or treatment and the availability of these' (Department of Health (DH), 2008). In Scotland, Living and Dying Well: Building on Progress (Scottish Government (SG), 2011) referred to adopting a 'thinking ahead' philosophy. PMID- 22067952 TI - Challenges facing newly qualified community nurses: a qualitative study. AB - This article describes a qualitative study that set out first to explore the challenges facing recently qualified nurses working in community and intermediate healthcare settings, and their perceptions of role and professional identity, and then to propose effective support structures. Data were gathered using individual interviews which were recorded, transcribed and analysed through categorization using four key themes: transition work; new learning; support and supervision; professional identity and integration. It was concluded that transition can be challenging and stressful but, despite the level of independent working in the community, participants can be helped to develop resilience by a supportive environment in which their developmental needs are identified and met. Recommendations are made concerning the need for a more structured and planned approach to induction and preceptorship. PMID- 22067953 TI - Link mentorship: improving support for pre-registration students and mentors. AB - A very distinct policy change has, over recent years in the UK, prompted a marked cultural change and a transition of health services from the acute sector to the community setting. This transition has a direct implication for current and future pre-registration nursing students and, therefore, for the mentors who support them in community placements. This article will explore and discuss an initiative to introduce a link mentor role to support and develop mentorship within community district nurse settings in respect of adult pre-registration nursing students. The role was implemented collaboratively between a Higher Education Institution (HEI) and practice. Initially 15 community nurses undertook the role which was evaluated after 6 months. Feedback from mentors was overwhelmingly positive and plans are in place to develop the initiative further. PMID- 22067954 TI - Non-pharmacological management of behavioural symptoms of dementia. AB - This article describes a 6-month pilot project in which a community mental health team provided a dementia inreach service into 4 care homes in Birmingham, UK. The project included analysis of the impact of the service at the end of the project as well as a literature review of dementia care in care homes, and especially the issue of antipsychotic medication use and non-pharmacological approaches in managing behavioural and psychological symptoms of dementia (BPSD). The project included training care home staff in the management of BPSD; 2 questionnaires distributed at the beginning of the project found that 65% of care home staff felt a need for education and awareness, practical problem-solving and counselling in managing BPSD. Self-reported knowledge of common mental health problems and dementia increased in care home staff at the end of the project by a margin of 7% and 11% respectively. Reported confidence in managing behavioural problems increased by 9% among care home staff at the end of the project. The project achieved regular monitoring of psychotropic medications, and enabled the discharge of 14 out of 63 existing patients in the selected homes. The project also provided guidance for non-pharmacological techniques for management of BPSD, which included relaxation techniques, distraction techniques, reality orientation, reminiscence work, needs led therapy, music therapy, person-centred approach and behaviour therapy. PMID- 22067955 TI - Protecting the health of offenders in prison and other places of detention. AB - The care of prisoners (offenders) in England lies with the Department of Health (DH) and the ability of the PCTs to commission services. In other countries of the UK this differs; in Scotland the Scottish Prison Service manages the responsibility of offender health, with responsibility resting with local health boards in Wales and the South Eastern Health and Social Care Trust in Northern Ireland. This article provides the community nurse with an overview of health protection in England's prisons and places of detention along with a review of communicable disease, immunization and infection prevention and control. General advice on legal obligations is provided with infection control principles and a discussion concerning incident and outbreak management. The role of the community nurse in the prison setting is no different to the role being undertaken in any other situation or environment where people require health care. Offenders are entitled to the same standards of healthcare as the general public. PMID- 22067956 TI - District nurses' use of social networking sites: caution required. AB - Although an increasingly popular form of online communication and social interaction, social network sites have to be used with caution by district nurses. In common with all health professionals, the scope of a district nurse's accountability extends to their online presence, and inappropriate remarks or pictures posted online can call into question the fitness to practise of the individual. In this article, Richard Griffith and Cassam Tengnah review your accountability, as it applies to your online presence, and discuss the Nursing and Midwifery Council's new advice to nurses and midwives on acceptable use of social networks. PMID- 22067957 TI - Diacylglycerol kinase zeta: at the crossroads of lipid signaling and protein complex organization. AB - Diacylglycerol (DAG) and phosphatidic acid (PA) are lipids with unique functions as metabolic intermediates, basic membrane constituents, and second-signal components. Diacylglycerol kinases (DGK) regulate the levels of these two lipids, catalyzing the interconversion of one to the other. The DGK family of enzymes is composed of 10 isoforms, grouped into five subfamilies based on the presence of distinct regulatory domains. From its initial characterization as a type IV DGK to the generation of mouse models showing its importance in cardiac dysfunction and immune pathologies, diacylglycerol kinase zeta (DGKzeta) has proved an excellent example of the critical role of lipid-metabolizing enzymes in the control of cell responses. Although the mechanism that regulates this enzyme is not well known, many studies demonstrate its subtle regulation and its strategic function in specific signaling and as part of adaptor protein complexes. These data suggest that DGKzeta offers new opportunities for therapeutic manipulation of lipid metabolism. PMID- 22067958 TI - The treatment of scaphoid nonunion using the Ilizarov fixator without bone graft, a study of 18 cases. AB - OBJECTIVES: Evaluating the safety and efficacy of the Ilizarov fine-wire compression/distraction technique in the treatment of scaphoid nonunion (SNU), without the use of bone graft. DESIGN: A retrospective review of 18 consecutive patients in one centre. PATIENTS AND METHODS: 18 patients; 17 males; 1 female, with a mean SNU duration of 13.9 months. Patients with carpal instability, humpback deformity, carpal collapse, avascular necrosis or marked degenerative change, were excluded. Following frame application the treatment consisted of three stages: the frame was distracted 1 mm per day until radiographs showed a 2 3 mm opening at the SNU site (mean 10 days); the SNU site was then compressed for 5 days, at a rate of 1 mm per day, with the wrist in 15 degrees of flexion and 15 degrees of radial deviation; the third stage involved immobilization with the Ilizarov fixator for 6 weeks. The technique is detailed herein. RESULTS: Radiographic (CT) and clinical bony union was achieved in all 18 patients after a mean of 89 days (70-130 days). Mean modified Mayo wrist scores improved from 21 to 86 at a mean follow-up of 37 months (24-72 months), with good/excellent results in 14 patients. All patients returned to their pre-injury occupations and levels of activity at a mean of 117 days. Three patients suffered superficial K wire infections, which resolved with oral antibiotics. CONCLUSIONS: In these selected patients this technique safely achieved bony union without the need to open the SNU site and without the use of bone graft. PMID- 22067959 TI - Vascular risk factors and cognitive impairment in a stroke-free cohort. AB - OBJECTIVE: To examine vascular risk factors, as measured by the Framingham Stroke Risk Profile (FSRP), to predict incident cognitive impairment in a large, national sample of black and white adults age 45 years and older. METHODS: Participants included subjects without stroke at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with at least 2 cognitive function assessments during the follow-up (n = 23,752). Incident cognitive impairment was defined as decline from a baseline score of 5 or 6 (of possible 6 points) to the most recent follow-up score of 4 or less on the Six item Screener (SIS). Subjects with suspected stroke during follow-up were censored. RESULTS: During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment. Baseline FSRP score was associated with incident cognitive impairment. An adjusted model revealed that male sex (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.43-1.77), black race (OR = 2.09, 95% CI 1.88-2.35), less education (less than high school graduate vs college graduate, OR = 2.21, 95% CI 1.88-2.60), older age (10-year increments, OR = 2.11, per 10-year increase in age, 95% CI 2.05-2.18), and presence of left ventricular hypertrophy (LVH, OR = 1.29, 95% CI 1.06-1.58) were related to development of cognitive impairment. When LVH was excluded from the model, elevated systolic blood pressure was related to incident cognitive impairment. CONCLUSIONS: Total FSRP score, elevated blood pressure, and LVH predict development of clinically significant cognitive dysfunction. Prevention and treatment of high blood pressure may be effective in preserving cognitive health. PMID- 22067962 TI - An enhancing brainstem lesion in a patient with a history of worldwide travel. PMID- 22067963 TI - Parkinson disease: the enteric nervous system spills its guts. AB - Lewy pathology in Parkinson disease (PD) extends well beyond the CNS, also affecting peripheral autonomic neuronal circuits, especially the enteric nervous system (ENS). The ENS is an integrative neuronal network also referred to as "the brain in the gut" because of its similarities to the CNS. We have recently shown that the ENS can be readily analyzed using routine colonic biopsies. This led us to propose that the ENS could represent a unique window to assess the neuropathology in living patients with PD. In this perspective, we discuss current evidence which indicates that the presence of ENS pathology may by exploited to improve our understanding and management of PD and likely other neurodegenerative disorders. PMID- 22067965 TI - Love lies bleeding--those who are left behind salute you. PMID- 22067964 TI - "The seagull cry" in internal carotid artery dissection. PMID- 22067966 TI - Morphometry of dermal nerve fibers in human skin. PMID- 22067967 TI - Pediatric sciatic neuropathies: a 30-year prospective study. PMID- 22067968 TI - Improvement of migraine headaches in severely obese patients after bariatric surgery. PMID- 22067969 TI - Teaching NeuroImages: granulomatous angiitis of the CNS associated with Hodgkin lymphoma. PMID- 22067970 TI - Teaching NeuroImages: mesial temporal sclerosis after a prolonged unprovoked seizure in an infant. PMID- 22067971 TI - Teaching video NeuroImages: shake Mom's hand to get the diagnosis. PMID- 22067972 TI - An unusual cause of symptomatic tension-type headache: hypertrophic branchial myopathy. PMID- 22067973 TI - A nonsense variation p.Arg325X in the vascular endothelial growth factor-A gene may be associated with congenital tricuspid aortic valve stenosis. AB - BACKGROUND: In our recent study, we first reported that mutation in vascular endothelial growth factor-A is associated with bicuspid aortic valve stenosis. However, to date no groups have explored the role of vascular endothelial growth factor-A variations in the aetiology of congenital tricuspid aortic valve stenosis. METHODS: We sequenced all eight coding exons and exon-intron boundaries of the vascular endothelial growth factor-A gene in deoxyribonucleic acid samples of a cohort of 32 sporadic patients with tricuspid aortic valve stenosis, 300 normal controls, and 103 disease controls - conotruncal defects - in order to identify sequence variants. RESULTS: We identified a c.973C > T heterozygous nonsense variation in exon 6 of the vascular endothelial growth factor-A gene in a patient with an isolated tricuspid aortic valve stenosis. The c.973C > T variation, which was absent in all controls, changes a highly conserved arginine at amino acid position 325 to a stop codon (p.Arg325X) and is predicted to produce a truncated protein of 324 amino acid residues. The proband's parents had a normal cardiac phenotype; however, his father was a carrier of the p.Arg325X variation, which indicates that the p.Arg325X variation is inherited and incompletely penetrant. CONCLUSION: We report for the first time that the p.Arg325X nonsense variation in the vascular endothelial growth factor-A gene may be associated with congenital tricuspid aortic valve stenosis. PMID- 22067974 TI - Study on formulation variables of methotrexate loaded mesoporous MCM-41 nanoparticles for dissolution enhancement. AB - The aim of this study was to develop methotrexate loaded mesoporous MCM-41 nanoparticles for improved dissolution of methotrexate. The mesoporous MCM-41 nanoparticles act as carrier for drug and increase the solubility of the drug. In order to achieve this objective small pore size MCM-41 nanoparticles have been synthesized followed by drug loading process. The process of drug loading was optimized using full 33 factorial design. With a view to obtain maximum drug loading three variables, concentration of drug solution, stirring rate, and drug:carrier ratio were optimized using a full 33 factorial design. Using statistically designed experiments, the inclusion of methotrexate in MCM-41 nanoparticles was successfully carried out to obtain a drug loading of about 48%. X-ray powder diffraction and differential scanning calorimetry revealed the presence of methotrexate in amorphous form and FT-IR spectroscopy showed the presence of light interactions between the silicate silanols and the drug. The decrease of Brunauer, Emmett and Teller specific surface area and pore volume between free MCM-41 and the inclusion compound was the proof of the presence of methotrexate inside the mesopores. The inclusion compound was submitted to in vitro dissolution tests and a remarkable dissolution rate improvement was observed in comparison to the crystalline drug in all tested conditions. PMID- 22067976 TI - Hospital admissions and pharmacotherapy before out-of-hospital cardiac arrest according to age. AB - BACKGROUND: The underlying etiology of sudden cardiac death varies with age and is likely to be reflected in type and number of healthcare contacts. We aimed to determine the specific type of healthcare contact shortly before out-of-hospital cardiac arrest (OHCA) across ages. METHODS: OHCA patients were identified in the nationwide Danish Cardiac Arrest Register and Copenhagen Medical Emergency Care Unit (2001-2006). We matched every OHCA patients with 10 controls on sex and age. Healthcare contacts were evaluated 30 days before event by individual-level linkage of nationwide registers. RESULTS: We identified 16,924 OHCA patients, median age 70.0 years (Q1-Q3: 59-80). OHCA patients had a higher number of hospitalizations and received more pharmacotherapy compared to the control population across all ages (p for difference <0.001). OHCA patients aged 70-79 and 80-89 years had the highest proportion of hospitalizations (70%) and pharmacotherapy (73%), respectively. In general, the association between OHCA and hospitalizations and pharmacotherapy was more pronounced among the youngest OHCA patients compared to controls. OHCA patients in age groups 14-19, 20-29, 30-39 were ~5 times more likely to be in contact with the healthcare service than the control population (p for difference <0.001). Similarly, OHCA patients in the oldest age groups (60-69, 70-79, 80-89, >89) were <2 times more likely to be in contact with the healthcare services shortly before OHCA compared to the control population (p for difference <0.001). CONCLUSION: Young OHCA patients are more likely to be in contact with the healthcare services compared with an age and sex matched control population suggestive of traits that make them stand out from the general population. PMID- 22067975 TI - Rapid Response Team composition, resourcing and calling criteria in Australia. AB - INTRODUCTION: Rapid Response Teams (RRTs) have been introduced into at least 60% of Intensive Care Unit (ICU) - equipped Australian hospitals to review deteriorating ward patients. Most studies have assessed their impact on patient outcome and less information exists on team composition or aspects of their calling criteria. METHODS: We obtained information on team composition, resourcing and details of activation criteria from 39 of 108 (36.1%) RRT-equipped Australian hospitals. RESULTS: We found that all 39 teams operated 24/7 (h/days), but only 10 (25.6%) had received additional funding for the service. Although 38/39 teams, were physician-led medical emergency teams, in 7 (17.9%) sites the most senior member would be unlikely to have advanced airway skills. Three quarters of calling criteria were structured into "ABCD", and approximately 40% included cardiac and/or respiratory arrest as a calling criterion. Thresholds for calling criteria varied widely (particularly for respiratory rate and heart rate), as did the wording of the worried/concerned criterion. There was also wide variation in the number and nature of additional activation criteria. CONCLUSIONS: Our findings imply the likelihood of significant practice variation in relation to RRT composition, staff skill set and activation criteria between hospitals. We recommend improved resourcing of RRTs, training of the team members, and consideration for improved standardisation of calling criteria across institutions. PMID- 22067977 TI - Multienzymatic amperometric biosensor based on gold and nanocomposite planar electrodes for glycerol determination in wine. AB - Amperometric biosensors based on gold planar or nanocomposite electrode containing multiwalled carbon nanotubes for determination of glycerol were developed. The biosensors were constructed by immobilization of a novel multienzyme cascade consisting of glycerol kinase/creatine kinase/creatinase/sarcosine oxidase/peroxidase between a chitosan "sandwich." A measuring buffer contained adenosine 5'-triphosphate (ATP), creatine phosphate, and an artificial electrochemical mediator ferrocyanide. The currents proportional to glycerol concentration were measured at working potential of -50 mV against Ag/AgCl reference electrode. The biosensors showed linearity over the ranges of 5-640 MUM and 5-566 MUM with detection limits of 1.96 and 2.24 MUM and sensitivities of 0.80 and 0.81 nA MUM(-1), respectively. Both types of biosensors had a response time of 70s. The biosensors demonstrated satisfactory operational stability (no loss of sensitivity after 90 consecutive measurements) and excellent storage stability (90% of the initial sensitivity after 15 months of storage at room temperature). The results obtained from measurements of wines correlated well with those obtained with an enzymatic-spectrophotometric assay. The presented multienzyme cascade can be used also for determination of triglycerides or various kinase substrates when glycerol kinase is replaced by other kinases. PMID- 22067978 TI - Internally quenched fluorescent peptide libraries with randomized sequences designed to detect endopeptidases. AB - Identification of synthetic peptide substrates for novel peptidases is an essential step for their study. With this purpose we synthesized fluorescence resonance energy transfer (FRET) peptide libraries Abz (or MCA)-GXXXXXQ-EDDnp and Abz (or MCA)-GXXZXXQ-EDDnp, where X consists of an equimolar mixture of all amino acids, the Z position is fixed with one of the proteinogenic amino acids (cysteine was excluded), Abz (ortho-aminobenzoic acid) or MCA ([7-amino-4 methyl]coumarin) is the fluorescence donor and Q-EDDnp (glutamine-[N-(2,4 dinitrophenyl)-ethylenediamine]) is the fluorescence acceptor. The peptide libraries MCA-GXXX?XXQ-EDDnp and MCA-GXXZ?XXQ-EDDnp were cleaved as indicated (?) by trypsin, chymotrypsin, cathepsin L, pepsin A, and Eqolisin as confirmed by Edman degradation of the products derived from the digestion of these libraries. The best hydrolyzed Abz-GXXZXXQ-EDDnp sublibraries by these proteases, including Dengue 2 virus NS2B-NS3 protease, contained amino acids at the Z position that are reported to be well accepted by their S(1) subsite. The pH profiles of the hydrolytic activities of these canonical proteases on the libraries were similar to those reported for typical substrates. The FRET peptide libraries provide an efficient and simple approach for detecting nanomolar concentrations of endopeptidases and are useful for initial specificity characterization as performed for two proteases secreted by a Bacillus subtilis. PMID- 22067980 TI - An artifact in studies of gene regulation using beta-galactosidase reporter gene assays. AB - Reporter gene assays are important tools for evaluating gene expression. A frequently used assay measures the activity of beta-galactosidase (beta-gal) expressed from lacZ in plasmid or genomic constructions. Such constructions are often used to interrogate the ability of DNA (query DNA), potentially encoding a transcription factor, to regulate in trans the expression of a promoter fused to the reporter lacZ. Query DNA is frequently inserted into a second plasmid within the alpha-subunit of beta-gal, interrupting its function. However, this plasmid can induce up-expression of beta-gal even when void of query DNA, leading to confusion between artifact and authentic regulation. PMID- 22067979 TI - A protein switch sensing system for the quantification of sulfate. AB - Protein engineering has generated versatile methods and technologies that have been instrumental in advancements in the fields of sensing, therapeutics, and diagnostics. Herein, we demonstrate the employment of rational design to engineer a unique bioluminescence-based protein switch. A fusion protein switch combines two totally unrelated proteins, with distinct characteristics, in a manner such that the function of one protein is dependent on another. Herein we report a protein switch sensing system by insertion of the sulfate-binding protein (SBP) into the structure of the photoprotein aequorin (AEQ). In the presence of sulfate, SBP undergoes a conformational change bringing the two segments of AEQ together, "turning on" bioluminescence in a dose-dependent fashion, thus allowing quantitative detection of sulfate. A calibration plot was obtained by correlating the amount of bioluminescence generated with the concentration of sulfate present. The switch demonstrated selectivity and reproducibility, and a detection limit of 1.6*10(-4)M for sulfate. Moreover, the sensing system was validated by performing sulfate detection in clinical and environmental samples, such as, serum, urine, and tap water. The detection limits and working ranges in all three samples fall within the average normal/recommended sulfate levels in the respective matrices. PMID- 22067981 TI - An acetic acid-based extraction method to obtain high quality collagen from archeological bone remains. AB - Human bones, recovered from excavations, are an important biological archive of information. In particular, the analysis of the collagen fraction is useful for paleodietary reconstruction, via light stable isotopes, and for (14)C dating. Generally, collagen extraction procedures do not prevent loss of integrity of proteins. As a consequence, information about the state-of-remains preservation is unavailable. Here we describe a "soft" nondestructive CH(3)COOH-based method to recover collagen from archaeological bones, and also to obtain material for successive isotopic analyses. Our isotopic measurements on the extracts indicate that the CH(3)COOH-based method of extraction may be routinely employed in the context of paleodiet studies. In addition, we propose that biochemical characterization by denaturant electrophoresis and Western blot on CH(3)COOH extracts may be used as a bone collagen quality indicator. PMID- 22067982 TI - Safety, efficacy, and tolerability of early initiation of noninvasive positive pressure ventilation in pediatric patients admitted with status asthmaticus: a pilot study. AB - OBJECTIVES: Although noninvasive positive pressure ventilation is increasingly used for respiratory distress, there is not much data supporting its use in children with status asthmaticus. The objective of this study was to determine safety, tolerability, and efficacy of early initiation of noninvasive positive pressure ventilation in addition to standard of care in the management of children admitted with status asthmaticus. STUDY DESIGN: A prospective, randomized, controlled, clinical trial. PATIENTS: Twenty patients (1-18 yrs old) admitted to the pediatric intensive care unit with status asthmaticus. METHODS AND MAIN RESULTS: Children were randomized to receive either noninvasive positive pressure ventilation plus standard of care (noninvasive positive pressure ventilation group) or standard of care alone (standard group). Improvement in clinical asthma score was significantly greater in noninvasive positive pressure ventilation group compared to standard group at 2 hrs, 4-8 hrs, 12-16 hrs, and 24 hrs after initiation of interventions (p < .01). A significant decrease in respiratory rate at >= 24 hrs oxygen requirement after 2 hrs was noted in noninvasive positive pressure ventilation group as compared to standard group (p = .01 and p = .03, respectively). Although statistically not significant, fewer children in the noninvasive positive pressure ventilation group required adjunct therapy compared to standard group (11% vs. 50%; p = .07). There were no major adverse events related to noninvasive positive pressure ventilation. Nine out of ten patients tolerated noninvasive positive pressure ventilation through the duration of the study; noninvasive positive pressure ventilation had to be discontinued in one patient because of persistent cough. CONCLUSIONS: Early initiation of noninvasive positive pressure ventilation, along with short acting beta-agonists and systemic steroids, can be safe, well-tolerated, and effective in the management of children with status asthmaticus. PMID- 22067983 TI - Automated respiratory cycles selection is highly specific and improves respiratory mechanics analysis. AB - OBJECTIVE: Selected optimal respiratory cycles should allow calculation of respiratory mechanic parameters focusing on patient-ventilator interaction. New computer software automatically selecting optimal breaths and respiratory mechanics derived from those cycles are evaluated. DESIGN: Retrospective study. SETTING: University level III neonatal intensive care unit. SUBJECTS: Ten mins synchronized intermittent mandatory ventilation and assist/control ventilation recordings from ten newborns. INTERVENTION: The ventilator provided respiratory mechanic data (ventilator respiratory cycles) every 10 secs. Pressure, flow, and volume waves and pressure-volume, pressure-flow, and volume-flow loops were reconstructed from continuous pressure-volume recordings. Visual assessment determined assisted leak-free optimal respiratory cycles (selected respiratory cycles). New software graded the quality of cycles (automated respiratory cycles). Respiratory mechanic values were derived from both sets of optimal cycles. We evaluated quality selection and compared mean values and their variability according to ventilatory mode and respiratory mechanic provenance. To assess discriminating power, all 45 "t" values obtained from interpatient comparisons were compared for each respiratory mechanic parameter. MEASUREMENTS AND MAIN RESULTS: A total of 11,724 breaths are evaluated. Automated respiratory cycle/selected respiratory cycle selections agreement is high: 88% of maximal kappa with linear weighting. Specificity and positive predictive values are 0.98 and 0.96, respectively. Averaged values are similar between automated respiratory cycle and ventilator respiratory cycle. C20/C alone is markedly decreased in automated respiratory cycle (1.27 +/- 0.37 vs. 1.81 +/- 0.67). Tidal volume apparent similarity disappears in assist/control: automated respiratory cycle tidal volume (4.8 +/- 1.0 mL/kg) is significantly lower than for ventilator respiratory cycle (5.6 +/- 1.8 mL/kg). Coefficients of variation decrease for all automated respiratory cycle parameters in all infants. "t" values from ventilator respiratory cycle data are two to three times higher than ventilator respiratory cycles. CONCLUSIONS: Automated selection is highly specific. Automated respiratory cycle reflects most the interaction of both ventilator and patient. Improving discriminating power of ventilator monitoring will likely help in assessing disease status and following trends. Averaged parameters derived from automated respiratory cycles are more precise and could be displayed by ventilators to improve real-time fine tuning of ventilator settings. PMID- 22067984 TI - Critical care for pediatric asthma: wide care variability and challenges for study. AB - OBJECTIVES: To describe pediatric severe asthma care, complications, and outcomes to plan for future prospective studies by the Collaborative Pediatric Critical Care Research Network. DESIGN: Retrospective cohort study. SETTING: : Pediatric intensive care units in the United States that submit administrative data to the Pediatric Health Information System. PATIENTS: Children 1-18 yrs old treated in a Pediatric Health Information System pediatric intensive care unit for asthma during 2004-2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirteen thousand five-hundred fifty-two children were studied; 2,812 (21%) were treated in a Collaborative Pediatric Critical Care Research Network and 10,740 (79%) were treated in a non-Collaborative Pediatric Critical Care Research Network pediatric intensive care unit. Medication use in individual Collaborative Pediatric Critical Care Research Network centers differed widely: ipratropium bromide (41% 84%), terbutaline (11%-74%), magnesium sulfate (23%-64%), and methylxanthines (0% 46%). Complications including pneumothorax (0%-0.6%), cardiac arrest (0.2%-2%), and aspiration (0.2%-2%) were rare. Overall use of medical therapies and complications at Collaborative Pediatric Critical Care Research Network centers were representative of pediatric asthma care at non-Collaborative Pediatric Critical Care Research Network pediatric intensive care units. Median length of pediatric intensive care unit stay at Collaborative Pediatric Critical Care Research Network centers was 1 to 2 days and death was rare (0.1%-3%). Ten percent of children treated at Collaborative Pediatric Critical Care Research Network centers received invasive mechanical ventilation compared to 12% at non Collaborative Pediatric Critical Care Research Network centers. Overall 44% of patients who received invasive mechanical ventilation were intubated in the pediatric intensive care unit. Children intubated outside the pediatric intensive care unit had significantly shorter median ventilation days (1 vs. 3), pediatric intensive care unit days (2 vs. 4), and hospital days (4 vs. 7) compared to those intubated in the pediatric intensive care unit. Among children who received mechanical respiratory support, significantly more (41% vs. 25%) were treated with noninvasive ventilation and significantly fewer (41% vs. 58%) were intubated before pediatric intensive care unit care when treated in a Pediatric Health Information System hospital emergency department. CONCLUSIONS: Marked variations in medication therapies and mechanical support exist. Death and other complications were rare. More than half of patients treated with mechanical ventilation were intubated before pediatric intensive care unit care. Site of respiratory mechanical support initiation was associated with length of stay. PMID- 22067985 TI - Dexmedetomidine and ketamine: an effective alternative for procedural sedation? AB - OBJECTIVES: Although generally effective for sedation during noninvasive procedures, dexmedetomidine as the sole agent has not been uniformly successful for invasive procedures. To overcome some of the pitfalls with dexmedetomidine as the sole agent, there are an increasing number of reports regarding its combination with ketamine. This article provides a descriptive account of the reports from the literature regarding the use of a combination of dexmedetomidine and ketamine for procedural sedation. DATA SOURCE: A computerized bibliographic search of the literature regarding dexmedetomidine and ketamine for procedural sedation. MEASUREMENTS AND MAIN RESULTS: The literature contains four reports with cohorts of more than ten patients with a total of 122 patients. Two of these studies were prospective randomized trials. Additionally, there are eight single case reports or small case series (six patients or less) with an additional 21 pediatric patients. When used together, dexmedetomidine may prevent the tachycardia, hypertension, salivation, and emergence phenomena from ketamine, whereas ketamine may prevent the bradycardia and hypotension, which has been reported with dexmedetomidine. An additional benefit is that the addition of ketamine to initiate the sedation process speeds the onset of sedation, thereby eliminating the slow onset time when dexmedetomidine is the sole agent. Although various regimens have been reported in the literature, the most effective regimen appears to be the use of a bolus dose of both agents, dexmedetomidine (1 ug/kg) and ketamine (1-2 mg/kg), to initiate sedation. This can then be followed by a dexmedetomidine infusion (1-2 ug/kg/hr) with supplemental bolus doses of ketamine (0.5-1 mg/kg) as needed. CONCLUSIONS: The available literature except for one trial is favorable regarding the utility of a combination of ketamine and dexmedetomidine for procedural sedation. Future studies with direct comparisons to other regimens appear warranted for both invasive and noninvasive procedures. PMID- 22067986 TI - Development of a bedside tool to predict time to death after withdrawal of life sustaining therapies in infants and children. AB - OBJECTIVES: To generate a preliminary bedside predictor of rapid time-to-death after withdrawal of support in children to help identify potential candidates for organ donation after circulatory death. DESIGN: Retrospective chart review. SETTING: Pediatric intensive care unit of an academic children's hospital. PATIENTS: All deaths in the pediatric intensive care unit from May 1996 to April 2007. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1389 deaths, 634 patients underwent withdrawal of support and 518 with complete data regarding demographics, life-supportive therapies, and end-of-life circumstances were analyzed. Three hundred seventy-three (72%) patients died within 30 mins of withdrawal and 452 (87%) died within 60 mins. Using multiple logistic regression, significant predictors of death within 30 or 60 mins (typical cut-off times for organ donation) were identified and a predictor score was generated. Significant predictors included: age 1 month or younger; norepinephrine, epinephrine, or phenylephrine >0.2 ug/kg/min; extracorporeal membrane oxygenation; and positive end-expiratory pressure >10 cmH2O; and spontaneous ventilation. Possible scores for the 30-min predictor ranged from -17 to 67; a score <=-9 predicted a 37% probability of death <= 30 mins, whereas a score >= 38 predicted an 85% probability of death within 30 mins. For the 60-min predictor, scores ranged from -21 to 38; score <=-10 predicted a 59% probability of death within 60 mins and a score >= 16 predicted a 98% probability of death within 60 mins. CONCLUSIONS: This tool is a reasonable preliminary predictor for death within 30 or 60 mins after withdrawal of support in terminally ill or injured children and might assist in identifying potential pediatric candidates for donation after circulatory death, although prospective validation is required. PMID- 22067987 TI - Quality of life of pediatric cardiac patients who previously required extracorporeal membrane oxygenation. AB - OBJECTIVES: We sought to assess quality of life of pediatric cardiac extracorporeal membrane oxygenation survivors. We hypothesized that these patients would have decreased quality of life when compared to that of a general U.S. population sample. DESIGN: Cross-sectional study. SETTING: Patient homes and Children's Hospital Boston. PATIENTS: Cardiac extracorporeal membrane oxygenation survivors currently 5-18 yrs old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Quality of life was assessed by parent proxy report using the Child Health Questionnaire Parent Form 50 and was compared to that of a general U.S. population sample and other cardiac populations. Factors associated with lower quality of life were sought. Physical summary scores for 41 cardiac extracorporeal membrane oxygenation survivors were lower than the mean of the general population sample (42.4 +/- 16.4 vs. 53.0 +/- 8.8; p < .001) but similar to those of children with Fontan physiology or an automatic implantable cardioverter defibrillator. Psychosocial summary scores in extracorporeal membrane oxygenation patients were not different from those of the general population (48.2 +/- 11.8 vs. 51.2 +/- 9.1; p = .11) or of other cardiac samples. Postcardiotomy extracorporeal membrane oxygenation, more noncardiac operations, total intensive care and hospital days, noncardiac medical conditions, medications, and the need for physical, occupational, or speech therapy were associated with low physical summary scores. More noncardiac operations, noncardiac medical conditions, and the need for special education, physical, occupational, or speech therapy were associated with low psychosocial summary scores. CONCLUSIONS: In pediatric cardiac extracorporeal membrane oxygenation survivors, the physical component of health-related quality of life is lower than that of the general population but similar to that of patients with complex cardiac disease, whereas psychosocial quality of life is similar to that of the general population and of other pediatric cardiac populations. PMID- 22067988 TI - ROPGAPs of Arabidopsis limit susceptibility to powdery mildew. AB - The barley ROP GTPase HvRACB is a susceptibility factor of barley to powdery mildew caused by the biotrophic fungus Blumeria graminis f.sp. hordei (Bgh). In a recent publication, we reported about a MICROTUBULE-ASSOCIATED ROP GTPASE ACTIVATING PROTEIN 1 (HvMAGAP1) of barley. Transient-induced gene silencing or overexpression of HvMAGAP1 resulted in enhanced or reduced susceptibility to Bgh, respectively, indicating a possible HvRACB-antagonistic function of HvMAGAP1 in interaction with Bgh. HvMAGAP1 also influences the polarity of cortical microtubules in interaction with Bgh. In AtROPGAP1 and AtROPGAP4, Arabidopsis homologs of HvMAGAP1, knock-out T-DNA insertions enhanced susceptibility of Arabidopsis to the virulent powdery mildew fungus Erysiphe cruciferarum, indicating functions of ROPGAPs in pathogen interaction of monocots and dicots. Here we discuss the role of AtROPGAP1 and AtROPGAP4 in Arabidopsis pathogenesis of powdery mildew in some more detail. PMID- 22067989 TI - Two Arabidopsis guard cell-preferential MAPK genes, MPK9 and MPK12, function in biotic stress response. AB - Abscisic acid (ABA) plays a major role in plant development and adaptation to severe environmental conditions. ABA evokes cellular events to regulate stomatal apertures and thus contributes to the plant's ability to respond to abiotic stresses. Reactive oxygen species (ROS) are produced in response to ABA and mediate ABA-induced stomatal closure. We have shown that two MAP kinases, MPK9 and MPK12, are highly and preferentially expressed in guard cells and function as positive regulators of ROS-mediated ABA signaling in guard cells. Cell biological and electrophysiological analyses demonstrated that MPK9 and MPK12 act downstream of ROS and cytosolic Ca2+ and upstream of anion channels in the guard cell ABA signaling cascade. Plant pathogens use stomata as the primary gateway to enter into their hosts, and previous studies have indicated crosstalk between ABA and defense signaling. Here we show that mpk9-1/12-1 double mutants are highly susceptible to Pseudomonas syringae DC3000 compared to WT plants. These results suggest that the regulation of stomatal apertures by MPK9 and MPK12 contributes to the first line of defense against pathogens. PMID- 22067990 TI - OsDIS1-mediated stress response pathway in rice. AB - Ubiquitin-mediated protein degradation has been well demonstrated as a key regulatory mechanism in response to drought stress in Arabidopsis. However, the biological function of most E3 ligase genes in drought response is still unknown in rice. We recently showed that OsDIS1 (Oryza sativa drought-induced SINA protein 1), a SINA type E3 ligase, is involved in the drought-stress signal transduction in rice. OsDIS1 plays a negative role in drought stress tolerance through the transcriptional regulation of diverse stress-related genes and also possibly through the posttranslational regulation of its interacting protein OsNek6 in rice. Here we also show that OsDIS1 interacts with OsSKIPa, a drought and salt stress positive regulator in rice. Based on these results, we propose a working model for the function of OsDIS1 in regulating the stress signaling pathway in rice. PMID- 22067991 TI - Arabidopsis TRAPPII is functionally linked to Rab-A, but not Rab-D in polar protein trafficking in trans-Golgi network. AB - The trans-Golgi network (TGN) in plant cells is an independent organelle, displaying rapid association and dissociation with Golgi bodies. In plant cells, the TGN is the site where secretory and endocytic membrane trafficking meet. Cell wall components, signaling molecules and auxin transporters have been found to undergo intracellular trafficking around the TGN. However, how different trafficking pathways are regulated and how different cargoes are sorted in the TGN is poorly defined in plant cells. Using a combined approach of genetic and in vivo imaging, we recently demonstrated that Arabidopsis TRAPPII acts in the TGN and is required for polar targeting of PIN2, but not PIN1, auxin efflux carrier in root tip cells. Here, we report that, TRAPPII in Arabidopsis is required for polar distribution of AUX1, an auxin influx carrier in protophloem cells and epidermal cells of Arabidopsis root tips. In yeast cells, TRAPPII serves as a guanine-nucleotide exchange factor (GEF) for Ypt1 and Ypt31/32 in late Golgi trafficking, while in mammalian cells, TRAPPII acts as a GEF for Rab1 (homolog of yeast Ypt1) in early Golgi trafficking. We show here that TRAPPII in Arabidopsis is functionally linked to Rab-A proteins, homologs of yeast Ypt31/32, but not Rab D proteins, homologs of yeast Ypt1 and animal Rab1 proteins. PMID- 22067992 TI - Glycerol-3-phosphate and systemic immunity. AB - Glycerol-3-phosphate (G3P), a conserved three-carbon sugar, is an obligatory component of energy-producing reactions including glycolysis and glycerolipid biosynthesis. G3P can be derived via the glycerol kinase-mediated phosphorylation of glycerol or G3P dehydrogenase (G3Pdh)-mediated reduction of dihydroxyacetone phosphate. Previously, we showed G3P levels contribute to basal resistance against the hemibiotrophic pathogen, Colletotrichum higginsianum. Inoculation of Arabidopsis with C. higginsianum correlated with an increase in G3P levels and a concomitant decrease in glycerol levels in the host. Plants impaired in GLY1 encoded G3Pdh accumulated reduced levels of G3P after pathogen inoculation and showed enhanced susceptibility to C. higginsianum. Recently, we showed that G3P is also a potent inducer of systemic acquired resistance (SAR) in plants. SAR is initiated after a localized infection and confers whole-plant immunity to secondary infections. SAR involves generation of a signal at the site of primary infection, which travels throughout the plants and alerts the un-infected distal portions of the plant against secondary infections. Plants unable to synthesize G3P are defective in SAR and exogenous G3P complements this defect. Exogenous G3P also induces SAR in the absence of a primary pathogen. Radioactive tracer experiments show that a G3P derivative is translocated to distal tissues and this requires the lipid transfer protein, DIR1. Conversely, G3P is required for the translocation of DIR1 to distal tissues. Together, these observations suggest that the cooperative interaction of DIR1 and G3P mediates the induction of SAR in plants. PMID- 22067993 TI - miR393: integrator of environmental cues in auxin signaling? AB - Auxin signalling and plant development depend on a family of partially redundant F-box receptors of the TIR1/AFB2 Auxin Receptor (TAAR) clade. We have recently shown that the post-transcriptional regulation of the Arabidopsis thaliana TAAR gene family invokes complex sRNA regulations during development. In leaves, the microRNA miR393 appears (1) to be primarily generated from one of the two genes, AtMIR393B, (2) to regulate the expression of all four members of the clade and (3) to initiate the formation of functional secondary siRNAs, named siTAARs, from TAAR transcripts themselves. Strikingly, mir393b-1 mutants, which are impaired in the biogenesis of miR393b and siTAARs, exhibit rather mild developmental defects. The known roles of miR393 in nitrate response, in defence against pathogenic bacteria and in plant development lead us to hypothesize that miR393 plays an important role to integrate complex environmental stimuli. PMID- 22067994 TI - Type 2 histone deacetylases play a major role in the control of elicitor-induced cell death in tobacco. AB - The cell death which characterizes the onset of the Hypersensitive Response (HR) is a very important weapon evolved by plants to block pathogen development. By the use of numerous plant/avirulent pathogen or plant/elicitor models, we have now obtained detailed signalling pathways allowing, after pathogen or elicitor perception, the control of the expression of specific sets of genes that contribute to cell death. However, our knowledge of the molecular actors involved in this process still remains limited. This is particularly true when regarding what happen in the nucleus. We recently reported that nuclear post-translational protein modifications are major processes that control cell death. Using the tobacco/cryptogein model, we showed that type 2 histone deacetylase activities, which act as negative regulators of cell death, depend on their phosphorylation status. In the present paper, we integrated all these results to propose a model depicting the putative nuclear signalling pathways controlling the establishment of cell death in tobacco in response to the cryptogein elicitor. This model highlights the role of the nuclear protein acetylation and phosphorylation in the establishment of plant defences. PMID- 22067995 TI - Carnivorous Utricularia: the buckling scenario. AB - We review recent results about the functioning of aquatic carnivorous traps from the genus Utricularia. The use of high speed cameras has helped to elucidate the mechanism at the origin of the ultra fast capture process of Utricularia, at a millisecond time scale. As water is pumped out of the trap, pressure decreases inside the trap and elastic energy is stored due to the change of shape of the trap body. This energy is suddenly released when the trap is fired: the trap door undergoes an elastical instability--buckling--which allows its fast and passive opening and closure. This mechanism is used by Utricularia both to catch preys touching its trigger hairs and to fire spontaneously at regular time intervals. The results leading to this interpretation are reviewed and discussed and suggestions for further work are briefly presented. PMID- 22067996 TI - Crosstalk between blue-light- and ABA-signaling pathways in stomatal guard cells. AB - We recently established an immunohistochemical method for the detection of blue light (BL)-induced and phototropin-mediated phosphorylation of plasma-membrane H+ ATPase in stomatal guard cells of Arabidopsis thaliana. This technique makes it possible to detect the phosphorylation/activation status of guard-cell H+-ATPase in the epidermis of a single rosette leaf, without the need to prepare guard-cell protoplasts (GCPs) from a large number of plants. Moreover, it can detect guard cell responses under more natural and stress-free conditions compared to using GCPs. Taking advantage of these properties, we examined the effect of abscisic acid (ABA) on BL-induced phosphorylation of guard-cell H+-ATPase by using ABA insensitive mutants. This revealed inhibition of BL-induced phosphorylation of guard-cell H+-ATPase via the early ABA-signaling components PYR/PYL/RCAR-PP2Cs SnRK2s, which are known to be early ABA-signaling components for a wide range of ABA responses in plants. PMID- 22067997 TI - Cell-specific compartmentation of mineral nutrients is an essential mechanism for optimal plant productivity--another role for TPC1? AB - Vacuoles of different leaf cell-types vary in their capacity to store specific mineral elements. In Arabidopsis thaliana potassium (K) accumulates preferentially in epidermal and bundle sheath cells whereas calcium (Ca) and magnesium (Mg) are stored at high concentrations only in mesophyll cells. Accumulation of these elements in a particular vacuole can be reciprocal, i.e. as [K]vac increases [Ca]vac decreases. Mesophyll-specific Ca-storage involves CAX1 (a Ca2+/H+ antiporter) and Mg-storage involves MRS2-1/MGT2 and MRS2-5/MGT3 (both Mg2+-transporters), all of which are preferentially expressed in the mesophyll and encode tonoplast-localised proteins. However, what controls leaf-cell [K]vac is less well understood. TPC1 encodes the two-pore Ca2+ channel protein responsible for the tonoplast-localised SV cation conductance, and is highly expressed in cell-types that not preferentially accumulate Ca. Here, we evaluate evidence that TPC1 has a role in maintaining differential K and Ca storage across the leaf, and propose a function for TPC1 in releasing Ca2+ from epidermal and bundle sheath cell vacuoles to maintain low [Ca]vac. Mesophyll-specific Ca storage is essential to maintain apoplastic free Ca concentration at a level that does not perturb a range of physiological parameters including leaf gas exchange, cell wall extensibility and growth. When plants are grown under serpentine conditions (high Mg/Ca ratio), MGT2/MRS2-1 and MGT3/MRS2-5 are required to sequester additional Mg2+ in vacuoles to replace Ca2+ as an osmoticum to maintain growth. An updated model of Ca2+ and Mg2+ transport in leaves is presented as a reference for future interrogation of nutritional flows and elemental storage in plant leaves. PMID- 22067998 TI - Cell wall integrity maintenance in plants: lessons to be learned from yeast? AB - The plant cell wall is involved in different biological processes like cell morphogenesis and response to biotic/abiotic stress. Functional integrity of the wall is apparently being maintained during these processes by changing structure/composition and coordinating cell wall with cellular metabolism. In S.cerevisiae a well-characterized mechanism exists that is maintaining functional integrity of yeast the cell wall during similar processes. During the last years it has become obvious that plants have evolved a mechanism to monitor and maintain functional integrity of their cell walls. However, our understanding of the mechanism is rather limited. The available evidence suggests that similar signaling cascades may be involved and particular protein activities may be conserved between plants and yeast. Here we review the available evidence briefly and highlight similarities between yeast and plants that could help us to understand the mode of action of the signaling cascades maintaining plant cell wall integrity. PMID- 22067999 TI - Vertebrate unfolded protein response: mammalian signaling pathways are conserved in Medaka fish. AB - The accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR). The ER stress signal is sensed and transmitted by a transmembrane protein(s) in the ER. The number of these transducers has increased with evolution, one in yeast, three in worm and fly, and five in mammals. Here, we examined medaka fish, Oryzias latipes, as a vertebrate model organism, and found that the medaka genome encodes five UPR transducers. Analysis of a medaka embryonic cell line revealed that the mammalian UPR signaling mechanisms are very well conserved. Thus, XBP1 mRNA, which encodes the transcription factor XBP1 downstream of the IRE1 pathway, was spliced in response to ER stress, resulting in production of the active form of XBP1. Translation was generally attenuated in response to ER stress, which paradoxically induced the translation of ATF4, the transcription factor downstream of the PERK pathway. ATF6 was constitutively synthesized as a transmembrane protein and activated by ER stress-induced proteolysis. Results obtained with the overexpression of active ATF6alpha, ATF6beta, and XBP1 strongly suggested that ATF6alpha plays a major role in upregulating the major ER chaperone BiP, contrary to the case in non-vertebrates, in which the IRE1 pathway is essential to the induction of BiP. Physiological ER stress occurring during embryonic development was visualized using transgenic medaka carrying the enhanced green fluorescent protein gene under the control of the BiP promoter. Thus, analysis of the vertebrate UPR using medaka will help provide a more comprehensive understanding of the biology and physiology of the UPR. PMID- 22068000 TI - Nursing in a changing NHS. AB - In the past few weeks, I have had the privilege of attending a series of seminars exploring the themes emerging from the Mid Staffordshire Public Inquiry to date. They are highly relevant to nurses and to the future of nursing. They have explored system and professional regulation, organizational culture, board leadership, information systems, nurse training, patient experience and commissioning. PMID- 22068001 TI - Abusing the privelege to care: shame on us. AB - Ian Peate, Consultant Editor of BJN, wrote the editorial 'Abusing the privelege: to care - shame on us' which was adapted and published on the BBC website (http://tinyurl.com/6cf2q5t). There was an overwhelming response to Ian's piece and some examples are shown here. PMID- 22068002 TI - Treating to target in rheumatoid arthritis: biologic therapies. AB - Treating to target is an established concept in the management of a number of long-term conditions to improve outcomes and prevent disease progression. Treatment targets in rheumatoid arthritis (RA) are to control the signs and symptoms of significant inflammatory disease activity, with the ultimate goal of remission from disease. The previous article in this series (Firth, 2011) outlined treating RA to target with conventional disease modifying drugs (DMARDs), including the role of the nurse in assessing disease activity, promoting shared clinical-decision making and monitoring treatment. In recent years, biologic agents have increased the treatment options for RA, but their use is reserved for patients with severe disease activity who fail to respond to treatment with two or more DMARDs. This article outlines the role of biologic therapies in treating RA to target, including eligibility criteria and the role of the nurse in optimizing outcomes. PMID- 22068003 TI - Critical care training: using Twitter as a teaching tool. AB - In 2010, the Joint Information Systems Committee (JISC) funded a project to explore the usefulness of Twitter as a teaching tool. The project, which was based at the Clinical Simulation Centre at the University of Glamorgan, involved the creation of four short, videoed clinical scenarios and used a high-fidelity mannequin-based simulator. A group of twelve learners on a BSc Critical Care course accessed these videos asynchronously and were encouraged to 'tweet' very short messages on the evolving condition of the patient in the videos, on key clinical decision points or respond to specific questions posted by the tutors. Another group of learners on a pre-registration nursing course used Twitter in a synchronous, face-to-face classroom environment and also tweeted their responses to the videos. The overall aim of the project was to explore the merits, or otherwise, of Twitter as a tool to scaffold learning and engage nursing students in reflection and clinical decision making. PMID- 22068004 TI - Developing a 'model of transition' prior to preceptorship. AB - It has long been recognized (Kramer, 1974) that the transition from student to qualified nurse or midwife is a steep learning curve which Kramer famously described as a 'reality shock'. The University Hospital of North Staffordshire (UHNS) NHS Trust has recently taken its established preceptorship programme a step further by integrating 'key' components into the final module (module 9) of nurse/midwifery training, now referred to as the 'transition' module. The development of this new and exciting 'shared learning' approach has been the result of collaborative working with the tutors at Keele University and the clinical education team at the UHNS Trust. The subject material introduced into module 9 aims to both reflect and support the current university curriculum. Initial verbal and written feedback from students who have progressed through the 'transition' module has been both positive and encouraging. Students have identified that they feel more prepared to take on their new roles, confident in the knowledge that they can seek support from the lead preceptor nurse/midwife prior to qualifying. PMID- 22068005 TI - The snapshot pre-registration assessment tool. Part 2: data, discussion and future directions. AB - This paper is the second of a two-part article presenting a new assessment tool (the snapshot) for pre-registration nurses in clinical practice that is being used at Kingston University/St George's University of London during year 3 of the Diploma and BSc programme. Part 1 of this article presented background to the snapshot tool and the research approach used in the evaluative research study. Part 2 will present the data collection, findings and discussion which show that the snapshot is perceived positively by students in terms of the criteria, documentation and process. However, mentor understanding of these factors varied with some mentors having an inadequate understanding and additional questions of assessment validity also arose and need to be addressed. Both parts of this article make a contribution to the practice assessment agenda and to the continuous clinical assessment methods currently in use that tests students' competence against agreed criteria. The snapshot reflects the reality of practice and assesses skills in a realistic environment. PMID- 22068006 TI - A right to die or a right to live? Discontinuing medical treatment. AB - This article explores the decision in the case of W v M, S and an NHS Primary Care Trust [2011] EWHC 2443 (Fam) in which an application to withdraw feeding from a woman in a minimally conscious state was rejected by Baker J in the Court of Protection. The article places the case in the context of the development of case law concerning the withdrawal of treatment from patients lacking decision making capacity, where death will be the inevitable consequence of the withdrawal of treatment after the decision in Airedale NHS Trust v Bland. It questions whether nearly two decades after the Bland decision there is scope for the boundaries of the decision to withdraw treatment from patients in 'futile' conditions to be reconsidered by the Supreme Court. PMID- 22068007 TI - The use of MRI scanning to triage patients. AB - The rise in the incidence of prostate cancer is mainly attributed to the increasing use of the serum prostate-specific antigen (PSA) blood test as a screening tool. Regardless of doubts over its sensitivity and specificity, PSA remain a key mechanism in the diagnosis and management of prostate cancer. The Department of Health (DH) in the UK recommends urgent specialist referral for patients presenting with age-elevated PSA. This national guideline, known as the National Cancer Wait Times (NCWT) system, aims at monitoring the process of referral, investigation and management of new suspicious prostate cancer cases. The use of transrectal ultrasound (TRUS) guided prostate biopsy is the gold standard specialist investigation for prostate cancer. However, there is growing interest in the use of imaging techniques like magnetic resonance imaging (MRI) as first-line specialist investigation for suspicious prostate cancer. PMID- 22068008 TI - Supporting the self and others: from staff nurse to nurse consultant. Part 12: series summary. AB - This series has examined a number of important structures and systems involved in supporting both yourself and others, in your work as a nurse. PMID- 22068009 TI - Meet the needs of older people. AB - The national report from the Care Quality Commission (CQC, 2011) detailed the findings of an inspection programme which looked at standards of dignity and nutrition in 100 NHS acute hospitals in England. The CQC carried out unannounced inspections at these hospitals in England between March and June 2011. Inspection teams were made up of CQC inspectors, a practising and experienced nurse, and an 'expert by experience' - someone with experience of caring or receiving care, trained and supported by Age UK. PMID- 22068010 TI - Duty of candour: can nurses lead the way in implementation? AB - Professor Alan Glasper discusses the Department of Health's Duty of Candour consultation, which is reminiscent of the NPSA's Being Open Framework in its aims for openness across health care and creating a more accountable and transparent NHS. PMID- 22068011 TI - Nutritional intervention and quality of life in palliative care patients. AB - Quality of life measures can be used by health professionals to assess effectiveness of nutritional interventions administered to palliative care patients. Stabilizing, maintaining and attempting to increase weight in palliative care patients through the support of oral feeding, and provision of artificial feeding, has been shown to mediate the metabolic and physical wasting effects of the disease process and improve general comfort. A quality of life instrument is a multi-dimensional questionnaire that health professionals can use to measure domains relating to physical, psychological and social aspects of living, and health and disease outcomes. There are three instruments specifically designed to assess quality of life in patients receiving palliative care. These are: The Palliative Care Quality of life Instrument, The Assessment of Quality of Life at the End of Life (AQEL), and The Spitzer Quality of Life Index (SQLI). General use quality of life measures are multifaceted; however, for use with palliative care patients, they have added dimensions of spirituality, existential issues (purpose and meaning of life), family members' perceptions of quality of care, symptom control and family support. Use of quality of life scales provides health professionals and organizations with an ideal measure for planning, targeting and evaluating health interventions. PMID- 22068012 TI - The importance of fastidiousness in nursing. AB - There has been a lot of criticism of nurses recently. Some would say that one of the biggest problems today is that nurses are not as disciplined or don't pay sufficient attention to detail. One hundred years ago in the BJN, there was an article questioning just how fussy and careful nurses were about small details such as dress and cleanliness. PMID- 22068013 TI - Kind enough to care, clever enough to cope. AB - In my lifetime the human race has reached out to the stars and walked on the surface of the moon. Now I can hold a computer more powerful than the one used to control the moon landing in the palm of my hand. Diseases that once signalled death have been reduced to the status of long-term conditions, the number of people aged 85 and over has more than tripled. PMID- 22068014 TI - Balancing quality and cost effectiveness. AB - It is not uncommon to open a nursing journal and be faced with dominating articles that focus on discussions around quality and cost-effective care. During this time of austerity, tissue viability services are not immune from the increasing pressure to improve patient care while reducing costs. PMID- 22068015 TI - Bioavailability, tissue distribution and hypoglycaemic effect of vanadium in magnesium-deficient rats. AB - Vanadium is an element whose role as a micronutrient and hypoglycaemic drug has yet to be fully clarified. The present study was undertaken to investigate the bioavailability and tissue distribution of vanadium and its interactions with magnesium in healthy and in magnesium-deficient rats, in order to determine its role as a micronutrient and antidiabetic agent. Four groups were used: control (456.4 mg magnesium and 0.06 mg vanadium/kg food); control treated with 1mg vanadium/day; magnesium-deficient (164.4 mg magnesium/kg food and 0.06 mg vanadium/kg food); and magnesium-deficient treated with 1 mg vanadium/day. The vanadium was supplied in the drinking water as bis(maltolato)oxovanadium (IV). The experiment had a duration of five weeks. We measured vanadium and magnesium in excreta, serum, skeletal muscle, kidney, liver, adipose tissue and femur. Fasting glucose, insulin and total antioxidant status (TAS) in serum were studied. The vanadium treatment applied to the control rats reduced the absorption, retention, serum level and femur content of magnesium. Magnesium deficiency increased the retention and serum level of vanadium, the content of vanadium in the kidney, liver and femur (organs where magnesium had been depleted), serum glycaemia and insulin, and reduced TAS. V treatment given to magnesium-deficient rats corrected magnesium content in muscle, kidney and liver and levels of serum glucose, insulin and TAS. In conclusion, our results show interactions between magnesium and vanadium in the digestive and renal systems. Treatment with vanadium to magnesium-deficient rats corrected many of the alterations that had been generated by the magnesium deficiency. PMID- 22068016 TI - Effects of dietary strawberry powder on blood lipids and inflammatory markers in obese human subjects. AB - Obesity is a strong risk factor for the development of CVD, hypertension and type 2 diabetes. The overall goal of the present pilot study was to feed strawberries, in the form of freeze-dried powder, to obese subjects to determine whether dietary strawberries beneficially altered lipid profiles and reduced blood markers of inflammation compared with a control intervention. A total of twenty healthy subjects (thirteen females and seven males) aged between 20 and 50 years with a BMI between 30 and 40 kg/m2 completed the present 7-week double-blind, randomised, cross-over trial. Each subject received a prepared diet 7 d/week for 7 weeks consisting of approximately 35 % of energy from fat, 20 % protein, 45 % carbohydrate and 14 g fibre. Blood was collected on days 1 and 8 for baseline information. After the first week, subjects were randomly assigned to the strawberry powder (equivalent to four servings of frozen strawberries) or control (strawberry-flavoured) intervention for 3 weeks. For the remaining 3 weeks, subjects crossed over to the opposite intervention. Blood was collected again at the end of weeks 3, 4, 6 and 7. A comprehensive chemistry panel, lipid profile analyses and measurement of inflammatory mediators were performed for each blood draw. A 3-week dietary intervention with strawberry powder reduced plasma concentrations of cholesterol and small HDL-cholesterol particles, and increased LDL particle size in obese subjects (P < 0.05). Dietary strawberry powder reduced risk factors for CVD, stroke and diabetes in obese volunteers, suggesting a potential role for strawberries as a dietary means to decrease obesity-related disease. PMID- 22068017 TI - Online first publication. PMID- 22068018 TI - High rates of intestinal colonization with extended-spectrum lactamase-producing Enterobacteriaceae among healthy individuals. AB - BACKGROUND: Infections caused by extended-spectrum beta-lactamase (ESBL) producing bacteria become an emerging problem in the community setting in many parts of the world. OBJECTIVE: The objective of the study was to determine fecal carriage of ESBL-producing organisms in a community setting. METHODS: A total of 632 fecal specimens from healthy individuals were screened for ESBL using the agar screening test with MacConkey agar plates supplemented with 1 MUg/mL of cefotaxime for selection of ESBL-producing strains and confirmed by the Clinical Laboratory Standards Institute combined disk method. RESULTS: Four hundred isolates (63.3%) were ESBL producers. Two hundred eighty-five isolates (71.25%) of them were Escherichia coli and 96 (24.0%) Klebsiella pneumoniae. CONCLUSION: We concluded that the community could be a reservoir of these ESBL-producing bacteria and enzymes. PMID- 22068019 TI - Evaluation of serum level of tumor necrosis factor receptor II in hepatitis C virus (genotype 4)-infected middle-aged men with and without diabetes and its complications in Egypt: a pilot study. AB - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is a type of cytokine produced by macrophages and other cell types in response to various stimuli. Many studies have shown that TNF-alpha is involved in the development of diabetes. It also has a pivotal role in the inflammatory process of chronic hepatitis C. OBJECTIVES: This study aimed to examine the hypothesis that TNF is increased in patients infected with hepatitis C virus (HCV) and with diabetes rather than in patients infected with HCV or with diabetes alone. METHODS: Patients were divided into 5 groups: patients with diabetes without complications and without HCV infection (group 1), patients with diabetes and complications but without HCV infection (group 2), patients without diabetes but with HCV infection (group 3), patients with diabetes without complications but with HCV infection (group 4), and patients with diabetes and complications and with HCV infection (group 5). RESULTS: Results revealed an activation of the TNF axis in all tested patients when compared with the level of healthy Egyptians done in previous studies. However, although there was a gradual escalation in the activation of the TNF axis in these groups, the increase did not amount to a statistical difference between them (P > 0.05). However, the trend was toward the higher values in HCV infection with diabetes and its complications. The number of studied patients may be a limitation of this research. There was no correlation between the level of TNF receptor II and the levels of transaminases, albumin, and creatinine in the different groups or the degree of microalbuminuria in the groups of patients with diabetic complications. Also, there was no relation between the hepatic or splenic size and the level of TNF receptor II. CONCLUSIONS: The presence of diabetes and its complications in patients with HCV infection could not be attributed only to the activation of the TNF system at least in Egyptian patients. PMID- 22068020 TI - A prokaryote-based cell-free translation system that efficiently synthesizes glycoproteins. AB - Asparagine-linked (N-linked) protein glycosylation has been observed in all domains of life, including most recently in bacteria and is now widely considered a universal post-translational modification. However, cell-based production of homogeneous glycoproteins for laboratory and preparative purposes remains a significant challenge due in part to the complexity of this process in vivo. To address this issue, an easily available and highly controllable Escherichia coli based cell-free system for the production of N-linked glycoproteins was developed. The method was created by coupling existing in vitro translation systems with an N-linked glycosylation pathway reconstituted from defined components. The translation/glycosylation system yielded efficiently glycosylated target proteins at a rate of hundreds of micrograms/milliliters in half a day. This is the first time a prokaryote-based cell-free protein synthesis system has generated N-linked glycoproteins. PMID- 22068021 TI - Ingestion of 10 grams of whey protein prior to a single bout of resistance exercise does not augment Akt/mTOR pathway signaling compared to carbohydrate. AB - BACKGROUND: This study examined the effects of a whey protein supplement in conjunction with an acute bout of lower body resistance exercise, in recreationally-active males, on serum insulin and insulin like growth factor 1 (IGF-1) and Akt/mTOR signaling markers indicative of muscle protein synthesis: insulin receptor substrate 1 (IRS-1), AKT, mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K) and 4E-binding protein 1 (4E-BP1). METHODS: In a randomized, double-blind, cross-over design, 10 males ingested 1 week apart, either 10 g of whey protein (5.25 g EAAs) or carbohydrate (maltodextrose), 30 min prior to a lower-body resistance exercise bout. The resistance exercise bout consisted of 4 sets of 8-10 reps at 80% of the one repetition maximum (RM) on the angled leg press and knee extension exercises. Blood and muscle samples were obtained prior to, and 30 min following supplement ingestion and 15 min and 120 min post-exercise. Serum and muscle data were analyzed using two-way ANOVA. RESULTS: No significant differences were observed for IGF-1 (p > 0.05). A significant main effect for Test was observed for serum insulin (p < 0.01) at 30 min post-ingestion and 15 and 120 min post-exercise, with no Supplement * Test interaction (p > 0.05). For the Akt/MTOR signaling intermediates, no significant Supplement * Test interactions were observed (p > 0.05). However, significant main effects for Test were observed for phosphorylated concentrations of IRS, mTOR, and p70S6K, as all were elevated at 15 min post-exercise (p < 0.05). Additionally, a significant main effect for Test was noted for 4E-BP1 (p < 0.05), as it was decreased at 15 min post-exercise. CONCLUSION: Ingestion of 10 g of whey protein prior to an acute bout of lower body resistance exercise had no significant preferential effect compared to carbohydrate on systemic and cellular signaling markers indicative of muscle protein synthesis in untrained individuals. PMID- 22068022 TI - Strategies toward single-donor islets of Langerhans transplantation. AB - PURPOSE OF REVIEW: The current review addresses a critical need in clinical islet transplantation, namely the routine transition from the requirement of two to four donors down to one donor per recipient. The ability to achieve single-donor islet transplantation will provide many more islet grafts for treatment of an ever-expanding patient base with type 1 diabetes (T1DM) with poor glycemic control. Avoiding exposure of recipients to multiple different donor human leukocyte associated (HLA) antigens is critical if risk of donor sensitization is to be avoided. This point is important as further islet or pancreas transplants in the remote future or the potential future need for a solid organ kidney transplant may become prohibitive if the recipient is sensitized. RECENT FINDINGS: This review addresses systematically all areas that contribute to the success or failure of single-donor islet engraftment, beginning with donor related factors, optimizing islet isolation and culture conditions, and describes a series of strategies in the treatment of the recipient to prevent inflammation, apoptosis, islet thrombosis, and improve metabolic functional outcome, all of which will lead to improved single-donor engraftment success. SUMMARY: If single donor islet transplantation can be achieved routinely, therapy will become more widely available, more accepted by the transplant community (currently pancreas transplantation requires only a single donor), and this situation will have a major impact overall as an effective treatment option in T1DM. PMID- 22068023 TI - Current world literature. PMID- 22068027 TI - Can community health workers increase coverage of reproductive health services? AB - BACKGROUND: Health services were severely affected during the many years of instability and conflict in Afghanistan. In recent years, substantial increases in the coverage of reproductive health services have been achieved, yet absolute levels of coverage remain very low, especially in rural areas. One strategy for increasing use of reproductive health services is deploying community health workers (CHWs) to promote the use of services within the community and at health facilities. METHODS: Using a multilevel model employing data from a cross sectional survey of 8320 households in 29 provinces of Afghanistan conducted in 2006, this study determines whether presence of a CHW in the community leads to an increase in use of modern contraceptives, skilled antenatal care and skilled birth attendance. This study further examines whether the effect varies by the sex of the CHW. RESULTS: Results show that presence of a female CHW in the community is associated with higher use of modern contraception, antenatal care services and skilled birth attendants but presence of a male CHW is not. Community-level random effects were also significant. CONCLUSIONS: This study provides evidence that indicates that CHWs can contribute to increased use of reproductive health services and that context and CHW sex are important factors that need to be addressed in programme design. PMID- 22068028 TI - Association between sleep duration and haemoglobin A1c in young adults. AB - BACKGROUND: Epidemiological and experimental evidence suggests that inadequate sleep can cause both obesity and impaired glucose tolerance. Short sleep duration in childhood appears to have a greater impact on the risk for adult obesity than adult sleep duration. The long-term effects of childhood sleep on glucose metabolism have not been investigated. The authors assessed the associations between childhood and adult sleep duration and adult glycosylated haemoglobin (HbA(1c)) levels. METHODS: An unselected cohort of 1037 individuals, born in Dunedin, New Zealand, between 1972 and 1973. Parent reports of times in bed at ages 5, 7, 9 and 11 were used to estimate childhood sleep duration. Adult sleep duration was estimated from self-reported times in bed at age 32. HbA(1c) levels were measured at age 32. Pregnant women and participants with diabetes were excluded from the analyses. RESULTS: Childhood sleep duration did not predict adult HbA(1c). However, less time spent in bed at age 32 was associated with higher levels of HbA(1c) (p=0.002) and an increased risk of prediabetes (p=0.015). The inverse association between adult sleep times and HbA(1c) was independent of body mass index, smoking, socioeconomic status, shift work and symptoms of obstructive sleep apnoea. CONCLUSIONS: Short sleep duration is associated with higher levels of HbA(1c) and an increased risk of prediabetes in young adults. The findings suggest that inadequate sleep impairs glucose control in the short term and may increase the risk for long-term health problems. PMID- 22068029 TI - Educational differences in disability pension among Swedish middle-aged men: role of factors in late adolescence and work characteristics in adulthood. AB - BACKGROUND: The association between level of education and disability pension (DP) is well known. Earlier studies have investigated the importance of early life factors and work characteristics but not in combination. The aim of this study was to investigate the association between level of education and DP among Swedish middle-aged working men and to what extent such an association can be explained by factors measured in late adolescence and work characteristics in adulthood. METHODS: Information about IQ, health-related lifestyle factors, psychiatric and musculoskeletal diagnoses was obtained from the 1969 conscription cohort, consisting of 49,321 Swedish men. Data collected when subjects were 18-20 years of age were combined with national register-based information about level of education, job control and physical strain at work in adulthood, and information about DP between 1991 and 2002. RESULTS: There was a strong graded association between level of education and DP. Those with the lowest level of education had a four times greater probability of having DP as compared with those with the highest level. In multivariable analyses, factors measured in late adolescence, IQ in particular, attenuated the association more than work-related characteristics in adulthood. CONCLUSIONS: The authors found an association between level of education and DP among Swedish middle-aged working men. A large part of the association was explained by factors measured in late adolescence, IQ in particular, and somewhat less by work characteristics measured in adulthood. Level of education remained as a significant predictor of DP in middle age after full adjustment. PMID- 22068030 TI - Neurons on Parafilm: versatile elastic substrates for neuronal cell cultures. AB - A variety of materials has been applied to neuronal cell culture substrates to improve the efficiency of the culture and to provide pertinent cell growth environment. Here we report the application of Parafilm((r)) M ('Parafilm') as a novel substrate for neuronal culture and patterning. Cell culture results show that elastic Parafilm had effects on cell viability, length and number of neurites, and soma spreading. Parafilm was also an effective substrate to obtain patterned neuronal cultures using a conventional micro-contract printing (MUCP) technique. Polylysine micropatterns in line or grid forms were readily transferred from PDMS stamp to bare Parafilm surfaces and spatially confined neuronal cultures were successfully maintained for over three weeks. We also demonstrate that batch-processing cell culture substrates can be easily fabricated using a piece of Parafilm. The softness, plasticity, and hydrophobicity were main features that made it attractive for Parafilm to be considered as a practical cell culture platform. The results can be extended to develop an inexpensive and practical neuronal culture substrates in tissue engineering and biochip applications. PMID- 22068031 TI - A robust experimental protocol for pharmacological fMRI in rats and mice. AB - Pharmacological Magnetic Resonance Imaging (phMRI) methods have significantly expanded the stimulation repertoire available to preclinical fMRI research, by allowing to selectively probe the activity of specific brain circuitries and neurotransmitter systems. However, the application of phMRI to animal models is constrained by a number of experimental factors. Firstly, in order to prevent motion artefacts and reduce restraint-induced stress, phMRI studies are typically performed under anaesthesia. Moreover, several psychoactive drugs produce blood pressure changes and alterations in respiratory frequency that may perturb central haemodynamic readouts of brain function. Hence, the quality and outcome of phMRI studies is critically dependent on the ability to monitor and control peripheral physiological parameters (i.e. blood pressure, arterial blood gases) that could alter phMRI readouts. Here we provide a thorough methodological description of a robust protocol to measure drug-induced cerebral blood volume changes in anaesthetised rats and mice. We show that the protocol ensures stable physiological parameters and robust phMRI response to the psychostimulant drug d amphetamine in three different rat strains. We also document the successful application of the protocol to map the central effects produced by d-amphetamine in C57Bl/6J mice, a strain commonly used as background for the generation of transgenic lines, thus paving the way to the implementation of phMRI in genetically engineered animals. PMID- 22068032 TI - Role of activation of 5'-adenosine monophosphate-activated protein kinase in gastric ulcer healing in diabetic rats. AB - BACKGROUND: The potential utility of 5'-adenosine monophosphate-activated protein kinase (AMPK)-activating agents, such as metformin, in inducing angiogenesis, could be a promising approach to promote healing of gastric ulcers complicated by diabetes mellitus. The aim of the present study was to assess the effect of a drug that activates AMPK, namely metformin, in gastric ulcer healing in streptozotocin-induced diabetic rats. METHODS: Forty male Wistar albino rats were made diabetic by intraperitoneal (i.p.) streptozotocin injection and 10 rats were injected i.p. by a single dose of physiological saline. Six weeks following streptozotocin or saline injection, gastric ulcers were induced by serosal application of acetic acid. Three days after acetic acid application, rats were divided into group 1 (nondiabetic control), group 2 (streptozotocin-injected rats), groups 3-5 (streptozotocin-injected rats treated with metformin or metformin and an inhibitor of AMPK, namely compound C or pioglitazone) for 7 days following acetic acid application. RESULTS: Administration of metformin, but not pioglitazone, resulted in a significant decrease in the gastric ulcer area, a significant increase in epithelial regeneration assessed histologically, a significant increase in the number of microvessels in the ulcer margin, a significant increase in gastric vascular endothelial growth factor concentration and gastric von Willebrand factor as well as a significant increase in gastric phospho-AMPK. Compound C, an inhibitor of AMPK, blocked metformin-induced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK. CONCLUSION: Our results suggest the feasibility of a novel treatment strategy, namely drugs activating AMPK, for patients in whom impairment of ulcer healing constitutes a secondary complication of diabetes mellitus. PMID- 22068033 TI - p53 modulates acquired resistance to EGFR inhibitors and radiation. AB - There is presently great interest in mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) inhibitors that are now being used widely in the treatment of a variety of common human cancers. To investigate these mechanisms, we established EGFR inhibitor-resistant clones from non-small cell lung cancer cells. A comparative analysis revealed that acquired resistance to EGFR inhibitors was associated consistently with the loss of p53 and cross resistance to radiation. To examine the role of p53, we first knocked down p53 in sensitive parental cells and found a reduction in sensitivity to both EGFR inhibitors and radiation. Conversely, restoration of functional p53 in EGFR inhibitor-resistant cells was sufficient to resensitize them to EGFR inhibitors or radiation in vitro and in vivo. Further studies indicate that p53 may enhance sensitivity to EGFR inhibitors and radiation via induction of cell-cycle arrest, apoptosis, and DNA damage repair. Taken together, these findings suggest a central role of p53 in the development of acquired resistance to EGFR inhibitors and prompt consideration to apply p53 restoration strategies in future clinical trials that combine EGFR inhibitors and radiation. PMID- 22068034 TI - Targeting regulatory T cells in cancer. AB - Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy. PMID- 22068035 TI - Expression and function of survivin in canine osteosarcoma. AB - Osteosarcoma has a high mortality rate and remains in need of more effective therapeutic approaches. Survivin is an inhibitor of apoptosis family member protein that blocks apoptosis and drives proliferation in human cancer cells where it is commonly elevated. In this study, we illustrate the superiority of a canine osteosarcoma model as a translational tool for evaluating survivin directed therapies, owing to the striking similarities in gross and microscopic appearance, biologic behavior, gene expression, and signaling pathway alterations. Elevated survivin expression in primary canine osteosarcoma tissue correlated with increased histologic grade and mitotic index and a decreased disease-free interval (DFI). Survivin attenuation in canine osteosarcoma cells inhibited cell-cycle progression, increased apoptosis, mitotic arrest, and chemosensitivity, and cooperated with chemotherapy to significantly improve in vivo tumor control. Our findings illustrate the utility of a canine system to more accurately model human osteosarcoma and strongly suggest that survivin directed therapies might be highly effective in its treatment. PMID- 22068036 TI - EZH2 Mediates epigenetic silencing of neuroblastoma suppressor genes CASZ1, CLU, RUNX3, and NGFR. AB - Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with an undifferentiated status and generally poor prognosis, but the basis for these characteristics remains unknown. In this study, we show that upregulation of the Polycomb protein histone methyltransferase EZH2, which limits differentiation in many tissues, is critical to maintain the undifferentiated state and poor prognostic status of NB by epigenetic repression of multiple tumor suppressor genes. We identified this role for EZH2 by examining the regulation of CASZ1, a recently identified NB tumor suppressor gene whose ectopic restoration inhibits NB cell growth and induces differentiation. Reducing EZH2 expression by RNA interference-mediated knockdown or pharmacologic inhibiton with 3-deazaneplanocin A increased CASZ1 expression, inhibited NB cell growth, and induced neurite extension. Similarly, EZH2(-/-) mouse embryonic fibroblasts (MEF) displayed 3 fold higher levels of CASZ1 mRNA compared with EZH2(+/+) MEFs. In cells with increased expression of CASZ1, treatment with histone deacetylase (HDAC) inhibitor decreased expression of EZH2 and the Polycomb Repressor complex component SUZ12. Under steady-state conditions, H3K27me3 and PRC2 components bound to the CASZ1 gene were enriched, but this enrichment was decreased after HDAC inhibitor treatment. We determined that the tumor suppressors CLU, NGFR, and RUNX3 were also directly repressed by EZH2 like CASZ1 in NB cells. Together, our findings establish that aberrant upregulation of EZH2 in NB cells silences several tumor suppressors, which contribute to the genesis and maintenance of the undifferentiated phenotype of NB tumors. PMID- 22068037 TI - The Multiverse of Inquiry: Introduction to the Special Issue on "Dementia Care and Chinese Culture" PMID- 22068038 TI - Youth on the virtual edge: researching marginalized sexualities and genders online. AB - Research shows clear links between lesbian, gay, bisexual, and transgender (LGBT) youth and deliberate self-harm (DSH), but there is a lack of research investigating the social context of young LGBT people's lives and helping to explain the higher DSH risk. In this article, we report on a small-scale methodological study intended to test the feasibility of online qualitative interviews for investigating young people, sexual and gender identity, and emotional distress. There are many methodological dilemmas arising from researching such sensitive issues with marginalized groups. The study reported here was designed to examine (a) sampling diversity in terms of sexuality, gender identities, and class; and (b) the type of data produced. We found that a virtual methodology was effective in recruiting young LGBT participants who might otherwise not take part in research. Online interviewing successfully produced in depth, "immediate" data that potentially gave access to insights that might not emerge through face-to face interviews. PMID- 22068039 TI - Young women's perspectives on cervical cancer prevention in Appalachian Kentucky. AB - Human papillomavirus (HPV) vaccination coupled with routine Papanicolaou (Pap) tests can prevent pervasive HPV infections causing cervical cancer. However, both HPV vaccination rates and Pap testing rates in Appalachian Kentucky are lower among all age groups than the rest of the United States. We recruited 19 young women residing in Appalachian Kentucky from university-based and rural clinical settings for group and individual interviews. After considering an integrated behavioral framework, we illustrate these women's perspectives by detailing five themes, including (a) experiential beliefs pose barriers to performing behaviors, (b) three vaccine doses complicate vaccination intention, (c) women have misunderstandings about HPV and the HPV vaccination function, (d) normative influences cue action (and inaction), and (e) specific environmental and contextual barriers exist to performing cervical cancer prevention behaviors in Appalachian Kentucky. These findings related to cervical cancer prevention in Appalachian Kentucky have implications for health-message design and clinical practice. PMID- 22068040 TI - Population health and social governance: analyzing the mainstream incorporation of ethnography. AB - Recently, health care workers (researchers, academics, policy writers, clinicians) have begun to view ethnography as an acceptable research methodology for informing public health work. This corresponds with a change in public health practice toward population health, wherein identifiable groups are examined to identify the group-level and contextual factors that affect their health statuses. Although population health-based methodological and outcomes-focused examinations have already occurred regarding ethnography, no extant literature scrutinizes the incorporation of ethnography into mainstream public and population health work from a sociopolitical viewpoint. Consequently, such an investigation occurs here using Foucault's concepts of discipline and Lupton's advancement of Foucault's ideas about the imperative of health. The outcome of this investigation is the assertion that ethnography is a strategic method for disciplining populations that do not respect the imperative of health. In other words, ethnography helps generate the data that can be used to normalize large groups of people. PMID- 22068041 TI - Intergenerational differences in food, physical activity, and body size perceptions among African migrants. AB - We assessed intergenerational differences in food, physical activity, and body size perceptions among refugees and migrants from the Horn of Africa living in Victoria, Australia. We used a qualitative design and obtained data from 48 participants (18 individual interviews; 3 semistructured focus groups). Three major themes emerged: (a) food and physical activity, (b) preference of body size and social expectations, and (c) perceived consequences of various body sizes. For parents, large body size was perceived to equate with being beautiful and wealthy; slimness was associated with chronic illness and poverty. Parents adopted strategies that promoted weight gain in children. These included tailored food practices and restricting children's involvement in physical activity. For young people, slimness was the ideal body size endorsed by their peers, and they adopted strategies to resist parental pressure to gain weight. Obesity-prevention programs in this subpopulation need to adopt a multigenerational approach. PMID- 22068042 TI - A history of interpersonal trauma and the gynecological exam. AB - Cervical cancer is preventable, in part, by routine Papanicolaou (Pap) testing, but some women avoid routine screening. African American women have the greatest mortality among all groups of women in the United States. Personal reasons have been found to contribute to screening avoidance behavior, such as a history of sexual abuse and intimate partner violence. Fifteen African American women with a trauma history participated in personal interviews. The Interaction Model of Client Behavior was employed for exploring the women's social influence, previous health care experience, cognitive appraisal, affective response, and motivation associated with routine Pap testing. Study findings suggest that providers need to assess and provide accurate information about Pap testing and cervical cancer to increase patients' knowledge. Personally reflecting on one's approach to conducting a woman's gynecologic exam (and how it is performed) might prevent triggering unwanted memories, making that visit a positive experience and facilitating repeat screening behavior. PMID- 22068043 TI - Fathers' beliefs about parenting and fathers' clubs to promote child health in rural Haiti. AB - Health care providers are challenged to use culturally appropriate, low technology approaches to improve child health in resource-poor countries. Village fathers' clubs is one approach used in rural Haiti since 1994. Fathers meet regularly for health education and community-building activities. Our aim was to investigate parenting practices and beliefs among Haitian fathers of young children and to explore their views on fathers' clubs. We conducted semistructured interviews with 18 fathers. Themes identified were fathers' involvement in routine care of their children, the close partnerships of fathers and mothers in child care, fathers' responsibilities to their communities, and fathers' clubs as an important supportive institution for the Haitian fathers and their families. Rural Haitian fathers reported taking a very active role in the lives of their families and children. Increased involvement of fathers should be explored as a strategy to improve child health and survival in other parts of Haiti and throughout the world. PMID- 22068044 TI - Sources of the uncertainty experienced by women with HPV. AB - Women with genital human papillomavirus (HPV) experience considerable stress and uncertainty as a result of the diagnosis; however, little is known about the sources of uncertainty in HPV. Given that uncertainty creates stress, which might be linked to the pathogenesis of cervical cancer, research on these sources of uncertainty is warranted. To this end, we completed semistructured interviews with 25 women living with HPV, and identified seven sources of uncertainty: The meaning of the diagnosis, the potential for disease progression, finances, the source of the infection, disclosure, sex and reproduction, and the HPV vaccine. In the discussion we articulate the relevance and importance of study findings to research, theory, and practice. PMID- 22068045 TI - Social contexts of risk behaviors for HIV among male, unskilled, unregistered laborers in urban Vietnam. AB - In Vietnam there has been relatively little success in controlling the HIV epidemic, in part because the subpopulations most exposed to the virus are often difficult to engage in prevention research and programs. In this qualitative study we explored social contexts shaping HIV risk behaviors among Vietnamese men involved in unskilled, unregistered, and low-income labor in urban settings. Based on self-disclosed behaviors, it is clear that these men were at high risk of sexually transmitted infection (STI). Evidence emerged from the interview data highlighting equivalent influences of individual psychological factors, social integration, social barriers, and accessibility regarding drug use and sexual risk behavior. Psychological influences such as tedium, distress, fatalism and revenge, and the strong effects of collective decision making and fear of social isolation appeared important for these men living on the economic and social margins of this rapidly urbanizing society. The study findings suggest directions for research and culturally appropriate HIV preventive education and services for these men. PMID- 22068046 TI - Disulfiram reaction in an artist exposed to solvents. AB - This case report describes an artist on treatment for alcoholism with disulfiram (Antabuse) who suffered chronic symptoms similar to those of a disulfiram alcohol reaction, which we attribute to his occupational exposure to products containing alcohol and other solvents. Symptoms abated with strict precautions to prevent exposure, although gradually returned over the course of months, causing him eventually to stop the medication. Medical practitioners should be aware of possible adverse interactions between occupational solvent exposures and disulfiram. PMID- 22068047 TI - Thymidine kinase and cancer monitoring. AB - Thymidine kinases (TK) have a key function in the synthesis of DNA. Two isoenzymes have been characterized: TK1 is cell cycle-dependent and present in the cytoplasm whereas TK2--located in mitochondria--is cell cycle-independent. The diagnostic and prognostic role of TK1 has recently been investigated. TK1 might be helpful for screening and monitoring of human malignancies. TK1 may also serve as a prognostic factor for progression. Herein, we summarize the status of TK1 for cancer monitoring and point out its use as a proliferation marker. A comprehensive overview about the association of TK-1 with various entities is given. PMID- 22068048 TI - Total isovolumic time relates to exercise capacity in patients with transposition of the great arteries late after atrial switch procedures. AB - BACKGROUND: Systemic right ventricular systolic dysfunction is common late after atrial switch surgery for transposition of the great arteries. Total isovolumic time is the time that the ventricle is neither ejecting nor filling and is calculated without relying on geometric assumptions. We assessed resting total isovolumic time in this population and its relationship to exercise capacity. METHODS: A total of 40 adult patients with transposition of the great arteries after atrial switch - and 10 healthy controls - underwent transthoracic echocardiography and cardiopulmonary exercise testing from January, 2006 to January, 2009. Resting total isovolumic time was measured in seconds per minute: 60 minus total ejection time plus total filling time. RESULTS: The mean age was 31.6 plus or minus 7.6 years, and 38.0% were men. There were 16 patients (40%) who had more than or equal to moderate systolic dysfunction of the right ventricle. Intra- and inter-observer agreement was good for total isovolumic time, which was significantly prolonged in patients compared with controls (12.0 plus or minus 3.9 seconds per minute versus 6.0 plus or minus 1.8 seconds per minute, p-value less than 0.001) and correlated significantly with peak oxygen consumption (r equals minus 0.63, p-value less than 0.001). The correlation strengthened (r equals minus 0.73, p-value less than 0.001) after excluding seven patients with exercise-induced cyanosis. No relationship was found between exercise capacity and right ventricular ejection fraction or long-axis amplitude. CONCLUSION: Resting isovolumic time is prolonged after atrial switch for patients with transposition of the great arteries. It is highly reproducible and relates well to exercise capacity. PMID- 22068049 TI - Lipid nanocapsule as vaccine carriers for his-tagged proteins: evaluation of antigen-specific immune responses to HIV I His-Gag p41 and systemic inflammatory responses. AB - The purpose of this study was to design novel nanocapsules (NCs) with surface chelated nickel (Ni-NCs) as a vaccine delivery system for histidine (His)-tagged protein antigens. Ni-NCs were characterized for binding His-tagged model proteins through high-affinity non-covalent interactions. The mean diameter and zeta potential of the optimized Ni-NCs were 214.9 nm and -14.8 mV, respectively. The optimal binding ratio of His-tagged Green Fluorescent Protein (His-GFP) and His tagged HIV-1 Gag p41 (His-Gag p41) to the Ni-NCs was 1:221 and 1:480 w/w, respectively. Treatment of DC2.4 cells with Ni-NCs did not result in significant loss in the cell viability up to 24h (<5%). We further evaluated the antibody response of the Ni-NCs using His-Gag p41 as a model antigen. Formulations were administered subcutaneously to BALB/c mice at day 0 (prime) and 14 (boost) followed by serum collection on day 28. Serum His-Gag p41-specific antibody levels were found to be significantly higher at 1 and 0.5 MUg doses of Gag p41 His-Ni-NCs (His-Gag p41 equivalent) compared with His-Gag p41 (1 MUg) adjuvanted with aluminum hydroxide (AH). The serum IgG2a levels induced by Gag p41-His-Ni NCs (1 MUg) were significantly higher than AH adjuvanted His-Gag p41. The Ni-NCs alone did not result in the elevation of systemic IL-12/p40 and CCL5/RANTES inflammatory cytokine levels upon subcutaneous administration in BALB/c mice. In conclusion, the proposed Ni-NCs can bind His-tagged proteins and have the potential to be used as antigen delivery system capable of generating strong antigen-specific antibodies at doses much lower than with aluminum-based adjuvant and causing no significant elevation of systemic pro-inflammatory IL-12/p40 and CCL5/RANTES cytokines. PMID- 22068050 TI - Design, modeling, and expression of erythropoietin cysteine analogs in Pichia pastoris: improvement of mean residence times and in vivo activities through cysteine-specific PEGylation. AB - In this study, the low-cost production of recombinant human erythropoietin cysteine analogs (Cys-rhEPOs) from Pichia pastoris and the potential to increase their serum residency and in vivo activity through cysteine-specific PEGylation were investigated. Three-dimensional structures of several Cys-rhEPOs were generated using homology modeling, and three stable Cys-rhEPOs were selected on the basis of model stability in molecular dynamics simulation and surface accessibility of the inserted cysteine. cDNAs encoding Cys-rhEPOs were constructed by site-directed mutagenesis and expressed as secreted proteins in flask cultures of P. pastoris. The selection of highly expressing clones and the optimization of certain culture parameters resulted in protein expression levels of 100-170 mg/l. Purified Cys-rhEPOs were cysteine-specifically PEGylated using 20 kDa and 30 kDa mPEG-maleimides (methoxy polyethylene glycol-maleimides). The E89CEPO analog with the highest (96.6%) cysteine accessibility was conjugated to PEG-polymers with the largest yields (about 80%). In comparison with rhEPO, 30 kDa PEG-E89CEPO demonstrated a significant (approximately 30%) increase in the mean residence time. Whereas the in vitro activities of 30 kDa PEG-E89CEPO were comparable to those of rhEPO, the in vivo activity of this conjugate was more prolonged compared to rhEPO (12 days vs. 7 days). Our results demonstrate that the site-specific PEGylation of Pichia-expressed EPO analogs may be considered as a promising approach for generating cost-effective and long-acting erythropoiesis stimulating agents. PMID- 22068051 TI - Autophagy-based unconventional secretory pathway for extracellular delivery of IL 1beta. AB - Autophagy controls the quality and quantity of the eukaryotic cytoplasm while performing two evolutionarily highly conserved functions: cell-autonomous provision of energy and nutrients by cytosol autodigestion during starvation, and removal of defunct organelles and large aggregates exceeding the capacity of other cellular degradative systems. In contrast to these autodigestive processes, autophagy in yeast has additional, biogenesis functions. However, no equivalent biosynthetic roles have been described for autophagy in mammals. Here, we show that in mammalian cells, autophagy has a hitherto unappreciated positive contribution to the biogenesis and secretion of the proinflammatory cytokine IL 1beta via an export pathway that depends on Atg5, inflammasome, at least one of the two mammalian Golgi reassembly stacking protein (GRASP) paralogues, GRASP55 (GORASP2) and Rab8a. This process, which is a type of unconventional secretion, expands the functional manifestations of autophagy beyond autodigestive and quality control roles in mammals. It enables a subset of cytosolic proteins devoid of signal peptide sequences, and thus unable to access the conventional pathway through the ER, to enter an autophagy-based secretory pathway facilitating their exit from the cytoplasm. PMID- 22068052 TI - An indirect role for ASPP1 in limiting p53-dependent p21 expression and cellular senescence. AB - In addition to acting as a transcriptional cofactor for p53, ASPP1 has been shown to function in the cytoplasm to regulate the nuclear localization and activity of YAP/TAZ. We show here that the ability of ASPP1 to activate YAP results in the decreased expression of LATS2, which lowers the ability of p53 to induce p21, cell-cycle arrest and senescence. ASPP1 expression peaks in S-phase, and down regulation of ASPP1 leads to a reduction in DNA synthesis and enhanced senescence in response to drugs that impede DNA replication. These activities of cytoplasmic ASPP1 in opposing p53-mediated p21 expression are in contrast to the role of nuclear ASPP1 in cooperating with p53 to induce the expression of apoptotic target genes, and may help to dampen p53 activity in normal cells. PMID- 22068053 TI - The unmasking of novel unipotent stem cells in the mammary gland. PMID- 22068054 TI - Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions. AB - The dorsal striatum is critically involved in a variety of motor behaviours, including regulation of motor activity, motor skill learning and motor response to psychostimulant and neuroleptic drugs, but contribution of D(2)R striatopallidal and D(1)R-striatonigral neurons in the dorsomedial (DMS, associative) and dorsolateral (DLS, sensorimotor) striatum to distinct functions remains elusive. To delineate cell type-specific motor functions of the DMS or the DLS, we selectively ablated D(2)R- and D(1)R-expressing striatal neurons with spatial resolution. We found that associative striatum exerts a population selective control over locomotion and reactivity to novelty, striatopallidal and striatonigral neurons inhibiting and stimulating exploration, respectively. Further, DMS-striatopallidal neurons are involved only in early motor learning whereas gradual motor skill acquisition depends on striatonigral neurons in the sensorimotor striatum. Finally, associative striatum D(2)R neurons are required for the cataleptic effect of the typical neuroleptic drug haloperidol and for amphetamine motor response sensitization. Altogether, these data provide direct experimental evidence for cell-specific topographic functional organization of the dorsal striatum. PMID- 22068055 TI - FOG-1 and GATA-1 act sequentially to specify definitive megakaryocytic and erythroid progenitors. AB - The transcription factors that control lineage specification of haematopoietic stem cells (HSCs) have been well described for the myeloid and lymphoid lineages, whereas transcriptional control of erythroid (E) and megakaryocytic (Mk) fate is less understood. We here use conditional removal of the GATA-1 and FOG-1 transcription factors to identify FOG-1 as required for the formation of all committed Mk- and E-lineage progenitors, whereas GATA-1 was observed to be specifically required for E-lineage commitment. FOG-1-deficient HSCs and preMegEs, the latter normally bipotent for the Mk and E lineages, underwent myeloid transcriptional reprogramming, and formed myeloid, but not erythroid and megakaryocytic cells in vitro. These results identify FOG-1 and GATA-1 as required for formation of bipotent Mk/E progenitors and their E-lineage commitment, respectively, and show that FOG-1 mediates transcriptional Mk/E programming of HSCs as well as their subsequent Mk/E-lineage commitment. Finally, C/EBPs and FOG-1 exhibited transcriptional cross-regulation in early myelo erythroid progenitors making their functional antagonism a potential mechanism for separation of the myeloid and Mk/E lineages. PMID- 22068057 TI - The role of RGS protein in agonist-dependent relaxation of GIRK currents in Xenopus oocytes. AB - G protein coupled inward rectifier K(+) channels (GIRK) are activated by the G(betagamma) subunits of G proteins upon activation of G protein coupled receptors (GPCRs). Receptor-stimulated GIRK currents are known to possess a curious property, termed "agonist-dependent relaxation," denoting a slow current increase upon stepping the membrane voltage from positive to negative potentials. Regulators of G protein signaling (RGS) proteins have earlier been implicated in this phenomenon since RGS coexpression was required for relaxation to be observed in heterologous expression systems. However, a recent study presented contrasting evidence that GIRK current relaxation reflects voltage sensitive agonist binding to the GPCR. The present study re-examined the role of RGS protein in agonist dependent relaxation and found that RGS coexpression is not necessary for the relaxation phenomenon. However, RGS4 speeds up relaxation kinetics, allowing the phenomenon to be observed using shorter voltage steps. These findings resolve the controversy regarding the role of RGS protein vs. GPCR voltage sensitivity in mediating agonist-dependent relaxation of GIRK currents. PMID- 22068056 TI - Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin remodelling complex. AB - Tissue-specific transcriptional activators initiate differentiation towards specialized cell types by inducing chromatin modifications permissive for transcription at target loci, through the recruitment of SWItch/Sucrose NonFermentable (SWI/SNF) chromatin-remodelling complex. However, the molecular mechanism that regulates SWI/SNF nuclear distribution in response to differentiation signals is unknown. We show that the muscle determination factor MyoD and the SWI/SNF subunit BAF60c interact on the regulatory elements of MyoD target genes in myoblasts, prior to activation of transcription. BAF60c facilitates MyoD binding to target genes and marks the chromatin for signal dependent recruitment of the SWI/SNF core to muscle genes. BAF60c phosphorylation on a conserved threonine by differentiation-activated p38alpha kinase is the signal that promotes incorporation of MyoD-BAF60c into a Brg1-based SWI/SNF complex, which remodels the chromatin and activates transcription of MyoD-target genes. Our data support an unprecedented two-step model by which pre-assembled BAF60c-MyoD complex directs recruitment of SWI/SNF to muscle loci in response to differentiation cues. PMID- 22068059 TI - Gastric trichobezoar: abdominal mass in a child with sickle cell disease. AB - Abdominal pain is a frequent occurrence among the pediatric population and can be a diagnostic challenge. Trichobezoar is a differential diagnosis that is often neglected. Different from previously reported cases, we present a 3-year-old girl with sickle cell disease with complaints of acute abdominal pain, suspecting sickle cell splenic sequestration. The child presented to the emergency department with sharp epigastric pain and an associated palpable upper abdominal mass. This case illustrates a large obstructing gastric trichobezoar and summarizes both the diagnostic modalities and treatment. PMID- 22068058 TI - Vulnerable child syndrome, parental perception of child vulnerability, and emergency department usage. AB - BACKGROUND: Vulnerable child syndrome (VCS) describes children perceived to be at risk for behavioral, developmental, or medical problems. Families with the dynamics of VCS overuse health care resources with frequent visits to doctors' offices. OBJECTIVE: The objective of the study was to explore the relationship between VCS, parental perception of child vulnerability (PPCV), and frequency of emergency department (ED) visits. DESIGN/METHODS: Parents of patients 1 to 15 years old presenting with nonurgent complaints to a pediatric ED were eligible. Participants completed questionnaires in which the Vulnerable Child Scale was used to generate a measure of PPCV. Primary outcomes included number of ED visits and PPCV assignment. Children were divided into 2 PPCV groups by Vulnerable Child Scale score: less than 40 (high PPCV) versus 40 or greater (low PPCV). The cutoff point was chosen as 1 SD (7.3) from the sample mean (46.8) on the vulnerable end of the scale (low scores). RESULTS: The mean ages of the 351 parents and children were 30 (SD, 7.7) years and 5 (SD, 3.9) years, respectively; 17% of children had high PPCV. Eleven variables differed statistically between subjects with high and low PPCV including number of ED visits and hospital admissions, excellent reported child health, pregnancy problems, delivery problems, child mental health problems, parent mental health problems, and child developmental problems. CONCLUSIONS: Our results reveal that children with higher PPCV had an increased number of ED visits, and risk factors for higher perceived vulnerability scores were identified. Future investigation on ways to intervene with families with the dynamics of VCS may be warranted. PMID- 22068060 TI - Optimizing patient/caregiver satisfaction through quality of communication in the pediatric emergency department. AB - BACKGROUND: Optimizing patient/family caregiver satisfaction with emergency department (ED) encounters has advantages for improving patient health outcomes, adherence with medical plans, patient rights, and shared participation in care, provider satisfaction, improved health economics, institutional market share, and liability reduction. The variables that contribute to an optimal outcome in the pediatric ED setting have been less well investigated. The specific hypothesis tested was that patient/family caregiver-provider communication and 24-hour postdischarge phone contact would be associated with an increased frequency of highest possible satisfaction scores. METHODS: A consecutive set of Press Ganey satisfaction survey responses between June and December 2009 in a large tertiary referral pediatric ED was evaluated. Press Ganey responses were subsequently linked to defined components of the electronic medical record associated with each survey respondent's ED visit to ascertain specific objective ED data. Multivariate modeling utilizing generalized linear equations was achieved to obtain a composite model of drivers of patient/caregiver satisfaction. RESULTS: Primary drivers of satisfaction and willingness to return or refer others to the ED were as follows: being informed about delays, ease of the insurance process, overall physician rating, registered nurse attention to needs, control of pain, and successful completion of postdischarge phone call to a family caregiver. Multiple wait time variables that were statistically significant in univariate modeling, including total length of time in the ED, time in waiting room, comfort of waiting room, time in treatment room, and play items, were not statistically significant once controlling for the other variables in the model. Type of insurance, race, patient age, or time of year did not influence the models. CONCLUSIONS: Achieving optimal patient/caregiver satisfaction scores in the pediatric ED is highly dependent on the quality of the interpersonal interaction and communication of ED activities. Wait time and other throughput variables are less important than perceived quality of the health interaction and interpersonal communication. Patient satisfaction has advantages greater than market share and should be considered a component of the care-delivery paradigm. PMID- 22068061 TI - Epidemiology and disposition of burn injuries among infants presenting to a tertiary-care pediatric emergency department. AB - OBJECTIVE: The objective of the study was to study the etiology of and factors determining the emergency department disposition of infants sustaining burn injuries. METHODS: A retrospective chart review was performed on all patients 12 months or younger with a burn injury presenting to our emergency department over a 5-year period. We collected the chief complaint and diagnosis, patient demographics, and circumstances surrounding the burn injury from the emergency department charts. Univariable statistics, multiple imputation, and multivariable regression were performed to determine differences between races and factors leading to admission. RESULTS: During the study period, 344 patients meeting inclusion criteria were treated in our emergency department. Scalds (53.2%) and contact burns (39.8%) were the most common causes of burns among the study group. Significant differences were observed between races for mechanism of burn, interhospital transport, and total body surface area affected (P < 0.05). White patients were more likely to have higher body surface affected and to be transferred from another facility (P < 0.05). Increased severity of burn, burns located on the hand, and concern for abuse resulted in higher likelihood of admission (P < 0.01). No significant differences in disposition or mechanism of burn were present between English-speaking and non-English-speaking patients. CONCLUSIONS: Although most infant burns in our emergency department are due to scalds, burn injuries due to contact with household objects are common. Race plays a significant role in mechanism and severity of burn sustained. Increased severity of burn, concern for abuse, and burn to the hand were all associated with increased odds of admission. PMID- 22068062 TI - Bedside ultrasound diagnosis of nonangulated distal forearm fractures in the pediatric emergency department. AB - OBJECTIVES: Ultrasound (US) may be a useful tool for rapidly diagnosing fractures. Our objective was to determine the accuracy of US as compared with radiographs in the detection of nonangulated distal forearm fractures. METHODS: Distal forearm US was performed and interpreted at the bedside by a pediatric emergency medicine physician before radiography in a prospective sample of children with possible nonangulated distal forearm fractures. A second pediatric emergency medicine physician with extensive US experience gave a final interpretation of the images. This second reviewer was blinded to both clinical and radiographic findings. The primary outcome was accuracy in the detection of fracture via the blinded reviewer's US interpretation when compared with the radiologist's clinical radiography results. Patient-reported FACES pain scores (range, 0-5) associated with both US and radiography were compared. RESULTS: Of 101 enrolled patients, 46 had a fracture detected by the radiologist. When compared with radiographs, the blinded US interpretation had an overall accuracy of 94% (95% confidence interval [CI], 88%-99%). Sensitivity and specificity were 96% (95% CI, 85%-99%) and 93% (95% CI, 82%-98%), respectively. Positive predictive value was 92%, and negative predictive value was 96%. Mean FACES pain scores were higher following radiography than US (1.7 vs 1.2, respectively; P = 0.004). CONCLUSIONS: For the diagnosis of nonangulated distal forearm fractures in children, bedside US holds promise as a diagnostic modality, particularly with appropriate training. Ultrasound is at least no more painful that traditional radiographs. Pediatric emergency medicine physicians should consider becoming proficient in this application. PMID- 22068063 TI - Impact of disaster drills on caregiver perception and satisfaction in the pediatric emergency department. AB - OBJECTIVE: The objective of this study was to assess caregiver perception and satisfaction of a regional disaster drill in a pediatric emergency department (ED). METHODS: Caregivers of children receiving care during a 2-hour disaster drill were given a survey regarding perceived importance of the drill, waiting time to see a physician, service timeliness, impact on comfort, and overall recommendation of the ED. As a control, the survey was also given to caregivers a week before and after the drill. RESULTS: Caregivers on the drill date were more likely to consider drill conduction to be highly important (100% vs 82.9%, P < 0.045). Compared with the drill date, there were no significant differences in the perceived duration of waiting, impact on care, or likelihood to recommend the ED to others. CONCLUSIONS: In a single regional disaster drill, we found that caregivers feel that disaster drills are important and unlikely to impact care of children negatively. These findings can help support decision making by hospital administrators to commit personnel and resources to conduct necessary disaster drills involving children. PMID- 22068064 TI - Bedside ultrasound in the diagnosis of pediatric clavicle fractures. AB - OBJECTIVE: The objective of the study was to determine the diagnostic accuracy of pediatric emergency physicians in diagnosing clavicle fractures by bedside ultrasound (US). METHODS: This was a prospective study of pediatric emergency department (ED) patients with suspected clavicle fractures conducted in a tertiary-care, freestanding pediatric hospital. A convenience sample of patients younger than 17 years underwent bedside US for detection of clavicle fracture by pediatric emergency physicians with limited US training. Ultrasound findings were compared with standard radiographs, which were considered the criterion standard. Pain scores using the validated color analog scale (0-10) were determined before and during US. Total length of stay in the ED, time to US, and time to radiograph were recorded. RESULTS: Fifty-eight patients were enrolled, of which 39 (67%) had fracture determined by radiograph. Ultrasound interpretation gave a sensitivity of 89.7% (95% confidence interval [CI], 75.8%-97.1%) and specificity of 89.5% (95% CI, 66.9%-98.7%). Positive and negative predictive values were 94.6% (95% CI, 81.8%-99.3%) and 81.0% (95% CI, 58.1%-94.5%), respectively. Positive and negative likelihood ratios were 8.33 and 0.11, respectively. Pain scores averaged 4.7 before US and 5.2 during US (P = 0.204). There was a statistically significant difference between mean time to US (76 minutes) and mean time to radiograph (107 minutes) (P < 0.001). CONCLUSIONS: Pediatric emergency physicians with minimal formal training can accurately diagnose clavicle fractures by US. In addition, US itself is not associated with an increase in pain and may reduce length of stay in the ED. PMID- 22068065 TI - Evaluation and management of sexually transmitted infections in adolescent males presenting to a pediatric emergency department: is the chief complaint diagnostic? AB - OBJECTIVES: The objectives of the study were to (1) describe evaluation and treatment patterns for adolescent males presenting with a concern for sexually transmitted infection (STI) in a pediatric emergency department, (2) assess the rates of STIs in symptomatic males, and (3) determine the utility of urinalysis alone in predicting STIs in adolescent males. METHODS: A retrospective cohort study was conducted of all patients presenting to our pediatric emergency department from January 1, 2007, to December 31, 2007. Inclusion criteria included males, aged 15 to 21 years, with an STI or urinary chief complaint. Exclusion criteria were referrals from pediatricians, a previous history of urinary tract infection or preexisting urologic condition, or primary complaint of scrotal and/or testicular pain. RESULTS: A total of 270 patients were identified. Testing included urinalysis with microscopy (UA) (64%), urine culture (53%), Neisseria gonorrhoeae (GC), and Chlamydia trachomatis (CT) (93%), and Trichomonas vaginalis (5%). Sixty-four percent of males tested positive for either GC or CT, or both. Overall, 91% of patients were treated for CT and GC, 18% for T. vaginalis, and 5% for urinary tract infection. The sensitivity and specificity of a positive UA for presence of GC and/or CT were 86% and 82%, respectively, whereas the positive and negative predictive values were 89% and 77%, respectively. There were no positive urine cultures in the cohort. CONCLUSIONS: Sixty-four percent of patients were diagnosed with either GC or CT. Although UA is helpful in predicting STI, limited use is warranted, given the high prevalence of disease in this selected population. The urine culture does not appear to be a necessary adjunct in the management of these patients. PMID- 22068066 TI - Does prearrival communication from a poison center to an emergency department decrease time to activated charcoal for pediatric poisoning? AB - OBJECTIVE: A poison center plays an important role in directing appropriate care, which is critical in reducing morbidity due to poisoning. Activated charcoal (AC) is one intervention for some poisonings. This study examined whether children with a poisoning who were preannounced by a poison center received AC earlier than patients without a referral. METHODS: A retrospective review of AC administration in children aged 0 to 18 years in a pediatric emergency department (ED) from 2000 to 2006 was performed. Abstracted covariates were poison center referral status, age, sex, acuity, disposition, transportation mode, triage time, and time of AC administration. Analysis of variance controlling for covariates tested the equality of mean time intervals between the groups with and without a poison center referral. RESULTS: Three hundred fifty-one cases met the inclusion criteria. One hundred thirty-five (39%) were male. Eighty cases (23%) had a poison center referral. Time from triage to charcoal administration for patients with a poison center referral was a mean of 59 (SD, 34) minutes. Time for the group without a referral was a mean of 71 (SD, 43) minutes (P = 0.0036). CONCLUSIONS: Advanced communication from a poison center was associated with earlier administration of AC in the ED for this population. Nevertheless, the duration to charcoal administration was frequently suboptimal. Triage and prehospital practices should be reexamined to improve timeliness of AC when indicated and consider exclusion of administration if beyond an appropriate time frame. Advanced notification should be the paradigm for all poison centers, and early response protocols for poison center referrals should be used by EDs. PMID- 22068067 TI - Trampoline trauma in children: is it preventable? AB - OBJECTIVES: Trampoline injuries represent a preventable cause of injury in children. This study identified the characteristics of children injured while using trampolines who presented to a pediatric trauma center in Sydney, Australia. METHODS: The Pediatric Trauma Database at our institution was reviewed to identify children with trampoline-related injuries between January 1999 and June 2008. Data collected included age, sex, Injury Severity Score, anatomical region injured, type of injury, mechanism of injury, site of injury and surface fallen onto, level of supervision, treatment, and hospital length of stay. RESULTS: Over the 9.5-year review period, 383 children presented with trampoline related injuries: 193 (50.4%) were female. Just over a quarter (n = 106, 27.7%) were treated and discharged the same day. The remaining patients accounted for 725 hospital bed days with a mean length of stay of 2.3 days. The most common area of the body injured was the upper limb (n = 246, 64.2%), with a fall from the trampoline to the ground being the most frequent mechanism of injury (n = 257, 67.1%). The majority (n = 345, 90.1%) of children were injured in their home or at the home of a friend or relative. Surgery was required in 236 (61.6%), with closed reduction of an upper limb fracture being the most common procedure (n = 107, 27.9%). CONCLUSIONS: Trampoline-related injuries remain common in children. Implementation of current guidelines and the introduction of innovative trampoline designs should reduce the risk of this injury in children. PMID- 22068068 TI - Is a lumbar puncture necessary when evaluating febrile infants (30 to 90 days of age) with an abnormal urinalysis? AB - OBJECTIVES: Guidelines for the management of febrile infants aged 30 to 90 days presenting to the emergency department (ED) suggest that a lumbar puncture (LP) should be performed routinely if a positive urinalysis is found during initial investigations. The aim of our study was to assess the necessity of routine LPs in infants aged 30 to 90 days presenting to the ED for a fever without source but are found to have a positive urine analysis. METHODS: We retrospectively reviewed the records of all infants aged 30 to 90 days, presenting to the Montreal Children's Hospital ED from October 2001 to August 2005 who underwent an LP for bacterial culture, in addition to urinalysis and blood and urine cultures. Descriptive statistics and their corresponding confidence intervals were used. RESULTS: Overall, 392 infants were identified using the microbiology laboratory database. Fifty-seven patients had an abnormal urinalysis. Of these, 1 infant (71 days old) had an Escherichia coli urinary tract infection, bacteremia, and meningitis. This patient, however, was not well on history, and the peripheral white blood cell count was low at 2.9 * 109/L. Thus, the negative predictive value of an abnormal urinalysis for meningitis was 98.2%. CONCLUSIONS: Routine LPs are not required in infants (30-90 days) presenting to the ED with a fever and a positive urinalysis if they are considered at low risk for serious bacterial infection based on clinical and laboratory criteria. However, we recommend that judicious clinical judgment be used; in doubt, an LP should be performed before empiric antibiotic therapy is begun. PMID- 22068069 TI - Benign afebrile convulsions in the course of mild acute gastroenteritis: a study of 28 patients and a literature review. AB - OBJECTIVES: Since the description of afebrile convulsions in the course of mild acute gastroenteritis (AGE) in 1982 by Morooka in Japan, there have been few reports of further cases outside Asia. The aim of this study was to share our casuistry--from a non-Asian country. METHODS: This is a retrospective study of identified cases in our center from January 2002 to December 2007. RESULTS: A total of 28 patients were studied. All were previously healthy patients who experienced convulsions with mild AGE without dehydration and with normal blood analysis. The mean age was 17.25 months (range, 6-48 months), with 93% younger than 24 months. Seizures were generalized tonic-clonic (61%), followed by generalized tonic (31%), and hypotonic (5.2%), with 2 (2.6%) partial. Only 8 patients (28.6%) presented one convulsion, and in 13 patients (46%), the seizures were in clusters from 3 to 6. Eleven patients (39%) presented 2 different types of convulsion. The duration of the crises ranged from 30 seconds to 10 minutes, and all of them occurred within 24 hours of the first. Electroencephalograms, obtained for all patients, were normal. Rotavirus was the main infectious agent in the AGEs, found in 11 patients with 22 determinations. In one patient, Salmonella serotype Enteritidis was isolated. All of the patients developed favorably, with no sequelae or epilepsy during the follow-up period. CONCLUSIONS: Afebrile convulsion in the course of mild gastroenteritis exists in our environment. It is a banal symptom in the course of the disease with good prognosis. Recognition of this fact may help avoid needless explorations and treatment in patients of this kind. PMID- 22068070 TI - Deadly proposal: a case of catecholaminergic polymorphic ventricular tachycardia. AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood. Catecholaminergic polymorphic ventricular tachycardia is a genetic cardiac channelopathy with known mutations involving genes affecting intracellular calcium regulation. We present a case of a 14-year-old boy who had cardiopulmonary arrest after an emotionally induced episode of CPVT while attempting to invite a girl to the school dance. Review of his presenting cardiac rhythm, induction of concerning ventricular arrhythmias during an exercise stress test, and genetic testing confirmed the diagnosis of CPVT. He recovered fully and was treated with beta-blocker therapy and placement of an implantable cardioverter-defibrillator. In this report, we discuss this rare but important entity, including its molecular foundation, clinical presentation, basics of diagnosis, therapeutic options, and implications of genetic testing for family members. We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome. PMID- 22068071 TI - Pediatric boutonniere deformity after blunt closed traumatic injury. AB - The boutonniere deformity (BD) is a well-described condition in hand surgery. Treatment of acute traumatic BD includes splinting of the proximal interphalangeal joint in extension for 4 to 5 weeks, which often leads to acceptable results. However, the chronic BD is more problematic and often requires surgical intervention with poor functional outcomes. Boutonniere deformity is extremely rare in the pediatric population. We present the case of a 9-year-old girl who presented to the emergency department with an acute traumatic BD after a fall. Being an uncommon entity in this patient population, the patient was referred to the plastic surgery clinic and was subsequently treated appropriately with splinting, resulting in favorable results as early as 4 weeks. To our knowledge, this is the first reported case of BD in the pediatric patient population. Recognition and timely management of BD in a pediatric patient should not be overlooked to obtain favorable results. PMID- 22068072 TI - Abusive suffocation presenting as new-onset seizure. AB - Child abuse can often be very difficult to identify. This is especially true in cases of abuse by suffocation. Suffocation often leaves no external physical marks and presents with vague, nonspecific symptoms. Infants who have been suffocated usually present unexplained apnea, cyanosis, or seizure. Moreover, new onset seizures can be mistaken for an organic seizure disorder. This case report reviews a case of abuse by suffocation, which presented as new-onset status epilepticus. This case illustrates that suffocation can be difficult to diagnose despite the recognition of red flags that should prompt an investigation for abuse. PMID- 22068073 TI - A life-threatening presentation of child physical abuse: jejunal perforation. AB - Intra-abdominal injuries from impacts are the second most common cause of death in battered children. However, it may be difficult to distinguish between accidental abdominal injury and abuse, especially in the absence of other clinical findings. Published reports are also limited about the diagnosis of abuse in children with intra-abdominal injury. We report a case with jejunal perforation, multiple soft tissue injuries, and occipital fracture secondary to child abuse who was initially admitted to our hospital with complaint of fever, cough, and vomiting. An exploratory laparotomy revealed perforation of the jejunum, and an end-to-end anastomosis was performed. The patient was evaluated by the hospital's child protective team to implement appropriate diagnostic and child-protective interventions, and the child was discharged home in 10 days. PMID- 22068074 TI - Lemierre syndrome in a 22-month-old due to Streptococcus pyogenes: a case report. AB - We report a case of Lemierre syndrome secondary to Streptococcus pyogenes in a 22 month-old girl. This case report and literature review took place at a pediatric intensive care unit at a freestanding tertiary children's hospital. Diagnosis occurred after the discovery of left internal jugular thrombus and multiple metastatic infection sites including the right knee, kidneys, lungs, and brain. Lemierre syndrome can occur in young children secondary to S. pyogenes, and a classic presentation may not occur. A high index of suspicion is crucial to the diagnosis. PMID- 22068075 TI - Asymptomatic complete atrioventricular block in a 13-year-old girl. AB - Atrioventricular (AV) block is a delay or an interruption in the transmission of an impulse from atria to ventricles due to an anatomic or a functional impairment in the conduction system. Atrioventricular block may be congenital or acquired. Electrocardiographic screening of asymptomatic school-aged children (median, 12.4 years) in Japan found the prevalence of a third-degree AV block to be 2 per 100,000. We report a case of asymptomatic complete AV block of unknown etiology in a 13-year-old child who did not require pacemaker placement. The importance of recognizing an asymptomatic complete AV block in the pediatric population, the classification and controversies of pacemaker placement, and the complications of pacemaker placement are discussed. PMID- 22068076 TI - A "rare" case of melena in a 3-year-old. AB - Melena is a potential sign of life-threatening upper gastrointestinal bleeding; however, there are numerous substances ingested resulting in a stool appearance similar to melena. Examples of such substances include black licorice, bismuth subsalicylate, and iron supplements. We report a case of a well-appearing 3-year old Vietnamese girl presenting to our emergency department after 2 episodes of "black, sticky" stool. The cause of her "melena" was determined after father revealed that she had ingested 2 bowls of pork blood soup during the preceding 12 hours. This case highlights the need for a careful dietary history and cultural considerations in children presenting with what may appear to be melena. PMID- 22068077 TI - Thrombotic thrombocytopenic purpura. AB - In 1924, Dr Eli Moschcowitz described a 16-year-old adolescent girl with abrupt onset of petechiae, hemolytic anemia, followed by paralysis, coma, and death. Autopsy showed widespread hyaline thrombi in the terminal arterioles and capillaries of various organs. The syndrome described by Moschowitz is now known as thrombotic thrombocytopenic purpura. PMID- 22068079 TI - Emergency department madness: tips to maintain sanity and flow. AB - Physician factors can influence congestion and wait times in emergency departments. This article provides some guidance to improve personal and departmental efficiency. PMID- 22068080 TI - Slipped capital femoral epiphysis. PMID- 22068081 TI - ECGs in the ED. PMID- 22068082 TI - Community pediatric hospitalists providing care in the emergency department: an analysis of physician productivity and financial performance. AB - OBJECTIVES: Community hospital pediatric inpatient programs are being threatened by current financial and demographic trends. We describe a model of care and report on the financial implications associated with combining emergency department (ED) and inpatient care of pediatric patients. We determine whether this type of model could generate sufficient revenue to support physician salaries for continuous in-house coverage in community hospitals. METHODS: Financial productivity and selected performance indicators were obtained from a retrospective review of registration and billing records. Data were obtained from 2 community-based pediatric hospitalist programs, which are part of a single health system and included care delivered in the ED and inpatient settings during a 1-year period from July 1, 2008, to July 1, 2009. RESULTS: Together, the combined programs were able to generate 6079 total relative value units and collections of $244,828 annually per full-time equivalent (FTE). Salary, benefits, and practice expenses totaled $235,674 per FTE. Thus, combined daily revenues exceeded expenses and provided 104% of physician salary, benefits, and practice expenses. However, 1 program generated a net profit of $329,715 ($40,706 per FTE), whereas the other recorded a loss of $207,969 ($39,994 per FTE). Emergency department throughput times and left-without-being-seen rates at both programs were comparable to national benchmarks. CONCLUSIONS: Incorporating ED care into a pediatric hospitalist program can be an effective strategy to maintain the financial viability of pediatric services at community hospitals with low inpatient volumes that seek to provide 24-hour pediatric staffing. PMID- 22068083 TI - Influenza vaccine update 2011-2012. PMID- 22068084 TI - Pneumoretroperitoneum after foreign body insertion. PMID- 22068106 TI - Arabidopsis thaliana Nudix hydrolase AtNUDT7 forms complexes with the regulatory RACK1A protein and Ggamma subunits of the signal transducing heterotrimeric G protein. AB - Arabidopsis thaliana AtNUDT7 Nudix pyrophosphatase hydrolyzes NADH and ADP-ribose in vitro and is an important factor in the cellular response to diverse biotic and abiotic stresses. Several studies have shown that loss-of-function Atnudt7 mutant plants display many profound phenotypes. However the molecular mechanism of AtNUDT7 function remains elusive. To gain a better understanding of this hydrolase cellular role, proteins interacting with AtNUDT7 were identified. Using AtNUDT7 as a bait in an in vitro binding assay of proteins derived from cultured Arabidopsis cell extracts we identified the regulatory protein RACK1A as an AtNUDT7-interactor. RACK1A-AtNUDT7 interaction was confirmed in a yeast two hybrid assay and in a pull-down assay and in Bimolecular Fluorescence Complementation (BiFC) analysis of the proteins transiently expressed in Arabidopsis protoplasts. However, no influence of RACK1A on AtNUDT7 hydrolase catalytic activity was observed. In vitro interaction between RACK1A and the AGG1 and AGG2 gamma subunits of the signal transducing heterotrimeric G protein was also detected and confirmed in BiFC assays. Moreover, association between AtNUDT7 and both AGG1 and AGG2 subunits was observed in Arabidopsis protoplasts, although binding of these proteins could not be detected in vitro. Based on the observed interactions we conclude that the AtNUDT7 Nudix hydrolase forms complexes in vitro and in vivo with regulatory proteins involved in signal transduction. Moreover, we provide the initial evidence that both signal transducing gamma subunits bind the regulatory RACK1A protein. PMID- 22068107 TI - Effects of low doses of gamma rays on the stability of normal and diabetic erythrocytes. AB - We studied the influence of low doses of gamma radiation (from 0.04 to 1.8 mGy) on the stability of human red blood cells (RBC) from healthy donors and diabetic patients using absorption spectroscopy. Because of the alteration of many enzymatic pathways in diabetic RBCs resulting in strong modification of the lipid and protein membrane components one could expect that the ionizing gamma radiation should influence the stability of the healthy and diabetic cells in a different way. Indeed, distinct discontinuities and monotonic changes of hemolysis detected in the healthy and diabetic RBCs suggest that various enzymatic and chemical processes are activated in these membranes by gamma radiation. Mossbauer measurements showed that only the highest applied dose of gamma radiation caused modification of hemoglobin in both types of RBCs. PMID- 22068108 TI - Direct interaction of Gas41 and Myc encoded by amplified genes in nervous system tumours. AB - In order to understand better the role of the human Tip60 complex component Gas41, we analysed its expression levels in brain tumours and searched for possible interactors. Two-hybrid screening of a human foetal brain library allowed identification of some molecular interactors of Gas41. Among them we found n-Myc transcription factor. The interaction between Gas41 and n-Myc was validated by pull-down experiments. We showed that Gas41 is able to bind both n Myc and c-Myc proteins, and that the levels of expression of Gas41 and Myc proteins were similar to each other in such brain tumors as neuroblastomas and glioblastomas. Finally, in order to identify which region of Gas41 is involved in the interaction with Myc proteins, we analysed the ability of Gas41 to substitute for its orthologue Yaf9 in yeast; we showed that the N-terminal portions of the two proteins, containing the YEATS domains, are interchangeable, while the C terminal portions are species-specific. In fact we found that Gas41 C-terminal portion is required for Myc protein interaction in human. PMID- 22068109 TI - Vertically-oriented conjugated polymer arrays in mesoporous alumina via simple drop-casting and appearance of anisotropic photoluminescence. AB - Vertically aligned fluorescent polymer arrays with poly(9,9-di-n-octylfluorenyl 2,7-diyl) (PFO) are prepared by simple drop-casting onto mesoporous alumina film. The obtained PFO arrays exhibit anisotropic photoluminescence (PL) along the orientation of the main chains. PMID- 22068110 TI - Insulin secretion and insulin sensitivity on the oral glucose tolerance test (OGTT) in middle-aged Japanese. AB - The aim of this study was to assess the changes in insulin secretion and insulin sensitivity in relation to fasting and 2-hour plasma glucose (PG) levels and to assess the independent contributions of their impairments to non-diabetic hyperglycemia. A total of 2157 Japanese workers (mean age 52.6+/-7.3 years and mean BMI 23.9+/-3.2 kg/m(2)) underwent an oral glucose tolerance test (OGTT). Of these subjects, 1125 had normal glucose tolerance (NGT), 525 subjects had isolated impaired fasting glucose (IFG), 159 subjects had isolated impaired glucose tolerance (IGT), 263 subjects had combined IFG and IGT, and 85 subjects had newly diagnosed type 2 diabetes. Insulinogenic index and Matsuda insulin sensitivity index (ISI) were significantly attenuated in subjects with normal but slightly elevated fasting PG, or in subjects with normal but slightly elevated 2 hour PG. Whereas, InsAUC(120)/GluAUC(120) was not significantly decreased in those subjects, and significant decrease of it was observed exclusively in subjects with abnormal fasting PG (>= 106 mg/dL) or abnormal 2-hour PG (>= 221 mg/dL). Using multiple regression analyses, both Matsuda ISI and insulinogenic index were independently correlated with PG concentrations in subjects with IFG and/or IGT, while Matsuda ISI alone was independently correlated with fasting PG concentrations in normoglycemic subjects. In conclusion, both insulinogenic index and Matsuda ISI were significantly attenuated in subjects with normal but slightly elevated PG. Lowering of Matsuda ISI was likely to be a strong contributor to 'elevation of fasting PG within the normal range' in this population. PMID- 22068111 TI - Resveratrol prevents streptozotocin-induced diabetes by inhibiting the apoptosis of pancreatic beta-cell and the cleavage of poly (ADP-ribose) polymerase. AB - Resveratrol (3,5,4'-trihydroxystilbene; RSV) is one kind of polyphenolic phytoalexin that has many effects on metabolic diseases. This study aimed to evaluate the protective effect of RSV pretreatment on beta-cell. Male Sprague Dawley rats weighing 200-230 g were divided into 4 groups: (1) RSV; (2) streptozotocin (STZ, 70 mg/kg, intraperitoneally); (3) STZ after 7 days pretreatment with RSV; and (4) STZ pretreated with nicotinamide. Fasting glucose concentration was measured and an intraperitoneal glucose tolerance test was performed 72 h after STZ injection to determine the diabetic condition. The pancreas was removed 3, 6, 36, and 48 h after STZ injection. STZ induced diabetes in all rats not given RSV pretreatment, whereas none of the RSV pretreated rats developed diabetes. Pretreatment with RSV inhibited apoptosis and reduced the activation of caspase-3 and poly(ADP-ribose) polymerase (PARP). However, expression of the total length PARP was not affected by pretreatment. Our findings suggest that RSV protects beta-cells from STZ simultaneously with inhibiting the activation of PARP. PMID- 22068112 TI - Combined treatment with bicalutamide and anastrozole in a young boy with peripheral precocious puberty due to McCune-Albright Syndrome. AB - McCune-Albright Syndrome (MAS) is a congenital endocrine disorder due to mosaic tissutal hyper-function. We describe a boy with a molecularly confirmed MAS, clinically evident with congenital cafe-au-lait spots, bone fibrous dysplasia, hyperthyroidism, and renal phosphate wasting syndrome. At 4.6 years of age he disclosed a rapid progression of peripheral puberty, so we decided to treat him with bicalutamide 25 mg/day and anastrozole 1 mg/day. Combined third generation aromatase inhibitors - competitive androgen receptor blockers were employed in familial male precocious puberty (FMPP). Combined treatment was performed for 49 months from the age of 4.6 to 6.7 years. The patient underwent clinical, laboratory, and instrumental evaluation twice a year from the first admission to the current age. This treatment caused a rapid normalization of growth velocity, subsequent reduction of penile androgenization, and stabilization of testicular volume. The therapy was well tolerated for all its duration and neither side effects, nor secondary hypothalamic activation were noted. This report provides further evidence of effectiveness and safety of combined third generation aromatase inhibitors - competitive androgen receptor blockers in male precocious peripheral puberty, firstly employed in male MAS, and contributes to expand the spectrum of disorders in which their employment may reveal promising. PMID- 22068113 TI - Early intensive insulin therapy attenuates the p38 pathway in the renal cortex and indices of nephropathy in diabetic rats. AB - In this rodent study, we compared the effects of early versus late intensive insulin therapy on diabetic nephropathy and potential causal mechanisms. Diabetes was induced in rats by high-fat diet and low-dose streptozotocin. Intensive insulin therapy was initiated in the early intensive insulin therapy groups as soon as diabetes was confirmed and lasted for 8 (8wEI group) and 16 weeks (16wEI group). In the late insulin therapy group (LI group), intensive insulin treatment was initiated 8 weeks later and lasted for 8 weeks. Age matched diabetic rats (8wDM group and 16wDM group) and non-diabetic rats (8wNC group and 16wNC group) served as controls. Histological analysis, real-time PCR, and western blot were performed in renal cortex specimens. Glomerular hypertrophy and mesangial matrix expansion were prominent in the 16wDM and LI groups while the EI groups remained normal and similar to the 16wNC group. Western blots revealed that p38 MAPK activities in the EI groups decreased significantly, whereas the level in the LI group was markedly higher than the 16wEI group, and not different from the DM groups. Activities of MKK3/6, CREB and MKP-1 proteins as well as CREB and MKP-1 mRNA showed a similar pattern. Therefore, we concluded that early intensive insulin treatment and attainment of good glycemic control counteracted some renal molecular pathways associated with epigenetic metabolic memory to minimize risk of diabetic nephropathy. However, late insulin therapy did not abrogate the increased renal cortical p38 MAPK pathway activation in diabetic rats and led to glomerular hypertrophy and extracellular matrix expansion. PMID- 22068115 TI - Palliative care research: urgent need for investment. AB - More so than for perhaps any other area of health care, the knowledge base supporting the basic elements of palliative care clinical practice is still lacking. Numerous reports have highlighted the critical need for research to advance the science of palliative care, but investments do not match this. A recent report on investment in palliative and end-of-life research in Canada revealed that for every $20 spent on cancer prevention services and basic research only $1 was spent on palliative care research (Canadian Cancer Research Alliance and Canadian Partnership Against Cancer, 2011); similar findings are reported for other countries. PMID- 22068114 TI - Prognosis of low-risk papillary thyroid carcinoma patients: its relationship with the size of primary tumors. AB - It is well-known that papillary thyroid carcinoma (PTC) has a generally indolent character and shows a favorable prognosis unless it has no high-risk features such as clinical lymph node metastasis, distant metastasis, and significant extrathyroid extension. In this study, we investigated the prognosis of 3,965 patients with PTC without these features. We classified these patients into 3 groups: T-1, tumor <= 2 cm (n = 2,591); T-2, tumor 2.1-4 cm (n = 1,123); T-3, tumor > 4 cm (n = 251). Ten-year recurrence rates of T-1, T-2, and T-3 patients were 0.3, 1.3, and 1.9% for the thyroid (in the subset of patients who underwent limited thyroidectomy), 1.9, 4.6, and 8.1% for lymph nodes, and 0.4, 1.6, and 3.4% for distant organs, respectively. A tumor size larger than 2 cm had an independent prognostic impact on all these recurrences also on multivariate analysis. These findings suggest that PTC larger than 2 cm exhibited more aggressive biological characteristics than that measuring 2 cm or less, even though it had no other high-risk features. However, the incidences of distant recurrence and carcinoma death were still low and it remains unclear whether extensive surgery is mandatory for otherwise low-risk PTC patients with large tumor. PMID- 22068116 TI - A global update on the development of palliative care services. AB - On World Hospice and Palliative Care Day-8 October 2011-the Worldwide Palliative Care Alliance (WPCA) launched a global update highlighting the progress that has been made in hospice and palliative care over the past 5 years (Lynch et al, 2011; WPCA 2011). Encouragingly, the study shows that there has been a marked increase in the number of countries providing one or more hospice and palliative care services-from 49% of countries in 2006 to 58% in 2011. Here we explore some of the key factors behind this progress, focusing particularly on advocacy and policy. PMID- 22068117 TI - Salivary gland dysfunction (dry mouth) in patients with advanced cancer. AB - Salivary gland dysfunction (SGD) is a common problem in patients with advanced cancer, and is associated with significant morbidity in this group of patients. The management of SGD involves treatment of the cause, treatment of the symptoms (preferably with saliva stimulants), prevention of the complications, and treatment of the complications. This article reviews the evidence for the clinical utility of various management strategies, highlighting those strategies that have been investigated in patients with advanced cancer. PMID- 22068118 TI - A learning and development strategy for children's hospices across London. AB - Over recent years there have been several political imperatives in the UK directed toward children's palliative care and ensuring that services are high quality, coordinated, family-centred, and able to meet the needs of children with complex disabilities. In addition, in 2010 the health and social care regulation authority in England-the Care Quality Commission (CQC)-aligned hospices with regulation and inspection requirements. This context has acted as a driver for the creation of effective education and training to ensure a skilled and expert workforce. Against this backdrop, this paper describes a project to develop a learning and development strategy for Children's Hospices across London (CHaL). CHaL educators worked with a research team to develop a unified strategy that was based on evidence of good practice, embedded in required CQC outcomes, and validated with a wider audience. The resultant strategy contains a set of four key learning and development principles that are applicable and transferable across different hospices. PMID- 22068119 TI - Analysis of a network-wide specialist palliative care out-of-hours advice and support line: a model for the future. AB - INTRODUCTION: Recently the palliative care literature has emphasized the need for 24-hour telephone advice and support for patients during the last year of life. As some health professionals may lack skills and knowledge regarding palliative care issues, an out-of-hours (OoH) advice line is considered a valuable resource. This report provides an analysis of both qualitative and quantative data concerning the Mount Vernon Cancer Network telephone advice line (TAL) for 2008 2010. METHOD: Data relating to the use of the TAL during OoH periods was collated and analysed on an annual basis. Data collected from a caller questionnaire relating to patient outcome, experience, and caller satisfaction was also evaluated. RESULTS: The number of calls to the OoH TAL increased by 13% over the 3-year period. The primary reason for the calls was symptom management, and 79% were made by patients' relatives. From the questionnaire responses, 66% of callers appeared to have a high rate of satisfaction, and 67% of patients were not admitted to hospital. CONCLUSIONS: It appears that the advice line is providing a highly valued service, with calls being managed by experienced nurses. Increasingly, local commissioners are placing greater emphasis on supporting care at home and reducing unnecessary hospital admissions, and advice lines seem to be an effective way of facilitating this. PMID- 22068120 TI - Evaluating a fast-track discharge service for patients wishing to die at home. AB - BACKGROUND: The UK Department of Health's End of Life Care Strategy highlighted the low percentage of patients who achieve their wish to die at home (~20%). Figures in south west London were below the London regional average. This paper reports an attempt to improve the proportion of patients from one hospital in the area achieving their preferred place of death. METHODOLOGY: A funded initiative by two local primary care trusts allowed the development of a 7-day-per-week fast track discharge service provided by the hospital palliative care team. The hospital team acted as coordinators, ensured that the correct medication and equipment would be available at the home, and personally transferred the patients to community services. RESULTS: Data is presented from the first representative period of fast-track discharging (June 2009-July 2010). A total of 110 discharges were facilitated over this time, with the rate increasing as the service developed. The vast majority of discharges occurred within 72 hours, and a significant number (~20%) occurred within 24 hours. CONCLUSIONS: The data indicate that the new service is effective. There are logistical problems in providing such a service and these are discussed. Further work is required to determine the feasibility of extending this service model to other acute hospitals and to evaluate its health-economic impact. PMID- 22068121 TI - Nurse-family interaction in Malaysian palliative care settings: a focused literature review. AB - BACKGROUND: Palliative care in Malaysia developed in the 1990s to improve the quality of life of people with advanced cancer. Like many other countries, Malaysia faces its own challenges in providing palliative care to patients and their families. In Malaysian culture, families play a significant part in providing care to the dying. Connecting with families in patient care is therefore important. This paper reports a focused literature review evaluating studies on the care of the families of terminally ill people in palliative care environments in Malaysia. METHOD: The search engines CINAHL, Medline, PsycINFO, and Google Scholar were searched for literature published from January 2000 to April 2010 relating to family care in palliative care environments. Due to a paucity of research on family care in Malaysia, the search was broadened to include relevant studies on family care internationally. RESULTS: Four themes were identified: delivering palliative care in Malaysia, communicating with families, crossing cultural boundaries, and the caring experience of nurses. CONCLUSION: The studies indicate the importance of the nurse-family interaction in providing optimal and culturally appropriate palliative care. This paper emphasizes the need for research into the nurse's role in family care and for developing a theory appropriate to the Malaysian culture and other countries with cultural diversity. PMID- 22068123 TI - Politics and palliative care: Germany. AB - Dion Smyth's review of the internet for palliative nursing. PMID- 22068124 TI - Infusion of Mg in humans acutely reduces serum insulin levels: a pilot study. AB - BACKGROUND: Infusion of Mg for therapeutic purposes is still a matter for debate. Dosages vary considerably, yet subclinical effects on normal physiology are largely ignored. In human and animal models, interactions between Mg and insulin exist, thus we have investigated the effect of infusing Mg on serum insulin, ionised Mg (Mg(2+)) and Ca (Ca(2+)) and plasma glucose in human volunteers. METHODS: Six male volunteers were infused with magnesium sulphate (MgSO(4)) dissolved in normal saline, using a high-dose "loading" bolus, followed by a lower-level "maintenance" period. FINDINGS: Serum Mg(2+) rose rapidly throughout the bolus infusion, declined during the maintenance phase, but remained higher than pre-infusion levels throughout the experimental period; serum Ca(2+) rose when serum Mg(2+) was highest. Infusion of MgSO(4) had no effect on heart rate or blood pressure, but caused a rapid, pronounced drop in circulating fasting insulin (p<0.0005), which slowly recovered to basal values during the course of the maintenance infusion. A slight, transient rise in plasma glucose (p<0.05) concomitant with the decline in serum insulin was also observed. INTERPRETATION: It is possible that the effect of Mg(2+) on insulin may have been due to antagonism of Ca(2+) entry in pancreatic beta-cells, the insulin decline causing a subsequent rise in circulating glucose levels. We suggest that these effects of MgSO(4) infusions should be considered where the aim is to achieve high doses of blood Mg(2+) levels by clinical intervention. PMID- 22068126 TI - Reproductive and developmental hazards. PMID- 22068125 TI - Natural recovery from antiglomerular basement membrane glomerulonephritis is associated with glomeruli-infiltrating CD8alpha+CD11c+MHC class II+ cells. AB - BACKGROUND/AIMS: In an antiglomerular basement membrane glomerulonephritis (GN) model, GN-resistant Lewis (LEW) rats naturally recover from early glomerular inflammation (days 21-23). We have previously identified a glomeruli-infiltrating CD8alpha(+)CD11(high)MHC II(+) cell (GIL CD8alpha(+) cell) in GN-prone Wistar Kyoto (WKY) rats, which terminates glomerular inflammation through inducing T cell apoptosis prior to glomerular fibrosis at days 35-40. We investigated if GIL CD8alpha(+) cells were also associated with the recovery in LEW rats. METHODS: GIL CD8alpha(+) cells in LEW rats were characterized; their infiltration was observed in connection with T cell apoptosis in glomeruli. RESULTS: An influx of GIL CD8alpha(+) cells into inflamed glomeruli was confirmed in the immunized LEW rats at days 17-22, which was much earlier than days 28-35 in WKY rats. Notably, LEW rats had a GIL CD8alpha(+)CD11(high) subpopulation after day 17, while WKY rats lacked this population until after day 30. Analyses further revealed a large number of clustered apoptotic CD4(+) or CD3(+) T cells in the glomeruli during recovery (day 23) in LEW rats, as compared to day 35 (transition to fibrosis) in WKY rats. Thus, infiltration of GIL CD8alpha(+) cells coincided with decline of glomerular inflammation and T cell apoptosis during recovery in LEW rats. Isolated GIL CD8alpha(+) cells were able to infiltrate glomeruli in both WKY and LEW rats at day 20. CONCLUSION: Our data revealed a strong association between GIL CD8a+ cells and recovery from early glomerular inflammation. It raises a possibility of involvement of GIL CD8a+ cells in the recovery. PMID- 22068127 TI - Are we focusing enough workplace wellness efforts on female workers? PMID- 22068128 TI - Short-term and long-term weight management results of a large employer-sponsored wellness program. AB - OBJECTIVE: To evaluate the weight management results of Healthy Incentives, an employer-sponsored wellness program started in 2006 by King County, Washington. METHODS: Changes in body mass index (BMI) and the percentages of those who lost 5% and 10% were compared for first-year participants, 5-year participants, and respondents to the Medical Expenditures Panel Survey (MEPS). RESULTS: A total of 19,559 first-year participants lost weight on average, while the comparative MEPS sample gained weight, -0.80% versus 0.31% (P < 0.01). A total of 10,432 5-year participants also lost weight on average but not as much as during the first year, -0.47% versus -0.80% (P = 0.01). More obese first-year participants lost 5% of BMI than the MEPS sample, 28.5% versus 23.2% (P < 0.01). Thirty eight percent of obese 5-year participants lost 5%. CONCLUSIONS: Healthy Incentives achieved significant weight management benefits for both first-year and 5-year participants. PMID- 22068129 TI - Occupational injury surveillance using the Washington State Trauma Registry. AB - OBJECTIVE: Traumatic injuries are a leading cause of death and disability among US workers, yet state trauma registries are rarely used for occupational research. Many, including the Washington State Trauma Registry, include information about work-relatedness. The objective is to explore and document the Washington State Trauma Registry as a resource for occupational injury surveillance and research. METHODS: State-designated trauma facilities report traumatic injuries meeting specific inclusion criteria to the Washington State Trauma Registry. This study included 16+ year-olds injured in Washington during 1998 to 2008. RESULTS: Of 125,625 injuries, 7.3% were work related. We found no evidence of downward trends in traumatic occupational injuries (2003 to 2008). CONCLUSIONS: Capturing industry and occupation would enhance utility for occupational injury surveillance and research. Trauma registry data could contribute to prevention planning/evaluation, improve case ascertainment for severe occupational injuries, and aid identification of high-risk populations and emerging trends. PMID- 22068130 TI - Lung cancer risk attributable to occupational exposures in a multicenter case control study in Central and Eastern Europe. AB - OBJECTIVE: To estimate the lung cancer risk attributable to occupational lung carcinogens. METHODS: Information was collected through interviews from 2624 newly diagnosed lung cancer cases and 2690 frequency-matched controls in Central and Eastern Europe. Industrial hygiene experts evaluated exposure to 70 occupational agents. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression and attributable fractions (AF) by Miettinen's formula. RESULTS: Exposure to at least one occupational lung carcinogen resulted in an AF of 7.9% in men and 1.4% in women. Metals and silica contributed the most to the AF. The AF was highest for squamous cell carcinoma among men (11.4%) and for small cell carcinoma among women (7.1%); the effect of occupational lung carcinogens was stronger overall among current smokers. CONCLUSION: This estimation of the AF of occupational lung carcinogens is comparable to that estimated in other European studies, and cannot alone explain the high lung cancer rates in Central and Eastern Europe. PMID- 22068131 TI - Soft-tissue sarcoma and pesticides exposure in men: results of a Canadian case control study. AB - OBJECTIVES: The objective was to investigate the putative associations of specific pesticides with soft-tissue sarcoma (STS). METHODS: A Canadian population-based case-control study conducted in six provinces was used in this analysis. The study design consisted of two stages: a self-administered postal questionnaire and a telephone interview for those reporting pesticides exposure of 10 hours per year or more; and a 15% random sample of the remainder. Conditional logistic regression was used to fit the statistical models. RESULTS: A positive history of cancer among first-degree relatives and exposure to aldrin and diazinon were statistically significant independent predictors of an increased risk for STS, whereas diagnosis of whopping cough lowered the risk of STS. CONCLUSIONS: The incidence of STS was associated with specific insecticides after adjustment for other independent predictors. PMID- 22068132 TI - Why are physicians subject to clinical guidelines? PMID- 22068136 TI - Current world literature. PMID- 22068135 TI - Site-selective modification of proteins for the synthesis of structurally defined multivalent scaffolds. AB - A combination of classical site-directed mutagenesis, genetic code engineering and bioorthogonal reactions delivered a chemically modified barstar protein with one or four carbohydrates installed at specific residues. These protein conjugates were employed in multivalent binding studies, which support the use of proteins as structurally defined scaffolds for the presentation of multivalent ligands. PMID- 22068138 TI - Challenging the received wisdom. PMID- 22068139 TI - Necrosis in breast cancer patients with skin metastases receiving bevacizumab based therapy. AB - OBJECTIVE: Bevacizumab has entered daily practice in advanced breast cancer patients, in whom skin metastases occurrence is a common event. Wound healing impairment has been described with bevacizumab, and this study looks at possible deleterious side effects of bevacizumab in patients with skin metastases. METHOD: We retrospectively reviewed a series of 12 patients with advanced breast cancer presenting extensive skin metastases, and who received bevacizumab based therapy. RESULTS: Nine patients who initially presented with erosive skin lesions developed extensive and durable skin necrosis, as well as delayed healing of surgical flaps, despite early discontinuation of bevacizumab therapy and intensive skin care in a specialised unit. Skin necrosis was usually associated with extensive tumoural involvement of the skin. CONCLUSION: Bevacizumab may be harmful in selected breast cancer patients with metastatic cutaneous involvement. PMID- 22068140 TI - An evaluation of the skin stripping of wound dressing adhesives. AB - OBJECTIVE: This study looks at six different modern wound dressings to investigate how likely they are to cause skin stripping and impairment of the skin's barrier function. METHOD: Healthy volunteers had each dressing applied, removed and reapplied to the skin on their back over the study period of 15 days. Skin barrier function was investigated using the amount of transepidermal water loss (TEWL) and then related to the amount of skin stripping, investigated by measuring stained skin removal, the thickness of the stratum corneum after treatment, and the amount of skin attached to the removed dressings. General signs of trauma, such as skin dryness and erythema, were investigated by subjective and objective parameters. RESULTS: TEWL values measured on the untreated test area, as well as after application of Urgotul Trio, remained relatively unchanged and Mepilex Border decreased slightly (?1g/m2/h), while all other dressings displayed an increased in TEWL: Allevyn Adhesive (5g/m2/h), Versiva XC (14g/m2/h), Comfeel Plus (22g/m2/h) and Biatain (28g/m2/h). By the end of the study, only the untreated area (mean 43% dye remaining), Mepilex Border (76%) and Urgotul Trio (34%) areas had visible dye remaining. It is interesting to note that the untreated site had a colour change, suggesting loss of stratum corneum, due to the shedding of skin cells from the surface. The increase in total skin colour for Comfeel Plus and Biatain after day 8 might be assigned to an increased redness due to erythema. All the dressings showed evidence of stratum corneum attached to the adhesive, except Mepilex Border, which appeared to be free of any attached stratum corneum. CONCLUSION: Overall the best performance in terms of skin protection and failure to cause skin trauma was found to be for Mepilex Border. CONFLICT OF INTEREST: This project was funded by a grant from Molnlycke Healthcare Ltd. PMID- 22068141 TI - Wound healing through synergy of hyaluronan and an iodine complex. AB - Hyaluronan, a glycosaminoglycan (GAG), is a polysaccharide found in many locations in the human body, such as eye, skin and soft tissue. It is also found in other mammals and bacteria. As a component of the extracellular matrix, its role in wound repair, among others, is that of providing a temporary structure to support new tissue formation. Harnessing the therapeutic action of hyaluronan into a topical application of proven clinical benefit has proved challenging. A new development in hyaluronan technology, comprising sodium hyaluronate and iodine complex, offers a novel approach in exploiting the benefits of hyaluronan and delivering real clinical benefits for a wide range of wound types. PMID- 22068142 TI - Wound dressings and other topical treatment modalities in bioburden control. AB - Reduction of wound bioburden has traditionally been achieved by the use of topical antimicrobial agents, such as bactericidal antiseptics or antibiotics. This has worked well for many years, however, concerns about toxicity and resistance have prompted research into other mechanisms. There are various means of removing bacteria from the wound, without recourse to chemical agents; for example, larvae (maggots) ingest bacteria, together with the devitalised tissue of the wound, while the control of exudate restricts the availability of free water, impeding the growth of water-loving bacteria. The discovery that some materials selectively adsorb, or sequester, bacteria has led to the development of bacteriostatic dressing materials, which do not rely on antiseptics for their action. These are designed to physically remove microorganisms, such as bacteria, from the wound, thus reducing bioburden. However, this still demands validation as a clinically relevant mechanism. Until that time, it remains a fascinating theoretical concept. This is a chapter taken from the book Microbiology of Wounds, published by CRC Press in 2010. PMID- 22068143 TI - Extended leg infection of diabetic foot ulcers: risk factors and outcome. AB - OBJECTIVE: To identify the risk factors for extension of infection to the leg in diabetic foot ulcers (DFU) and to evaluate its role as a prognostic measure regarding limb salvage and healing time. METHOD: This retrospective case-control study took place in Jabir Abu Eliz Diabetic (JADC) during 2006-2008. Forty-eight patients diagnosed with a diabetic foot ulcer (DFU) with the infection extending to the leg (case group) were compared with an equal number of patients with a DFU without extension (control group). Risk factors for extension were identified by univariate analysis and both groups were compared with regard to limb salvage and healing time. RESULTS: Previous history of toe amputation was more frequent in the case group (p=0.004). The case group patients were significantly more likely to present with fever (p=0.01), pallor (p=0.02), confusion (p=0.04), and necrosis (p=0.004). Ulcers located in the heel were more frequent in the case group when compared with controls (p=0.0001) while more toes ulcers were found in the control group (p=0.001). A significant number of patients in the case group had an ulcer of more than 5cm diameter compared with those in the control group (p=0.001). The total number of patients presented with severe disease (Wagner grade 3-5) was significantly more in the case group compared with controls (p=0.004). Patients with severe infection (grade 4) were more in the case group compared with the controls (p=0.04). There were no significant differences between the two groups with regard to major and minor amputation rate. The case group had a longer duration of healing when compared with the controls. Seventy five per cent of the controls healed by 6 months (n=31) compared with 22% in the case group (n=8 ; p=0.001). CONCLUSION: Toe amputation, wound located in the heel, wound size more than 5cm and advanced Wagner grade (3-5) and severe sepsis, grade 4, may be considered as risk factors for extension of infection to the leg in DFU. However, this extension did not carry a poor prognostic value to the final outcome if adequate therapeutic measures were followed. PMID- 22068144 TI - Innovation in tissue viability documentation for acute services. AB - This paper discusses the developmental process, outcome and delivery of an innovative approach to standardising tissue viability documentation across two sites within Nottingham University Hospitals NHS Trust, following the results of benchmarking pressure ulcer preventive care strategies and recommendations from pressure ulcer root cause analysis. It reflects upon the process, highlighting the lessons learnt. PMID- 22068145 TI - Functional analysis reveals the possible role of the C-terminal sequences and PI motif in the function of lily (Lilium longiflorum) PISTILLATA (PI) orthologues. AB - Two lily (Lilium longiflorum) PISTILLATA (PI) genes, Lily MADS Box Gene 8 and 9 (LMADS8/9), were characterized. LMADS9 lacked 29 C-terminal amino acids including the PI motif that was present in LMADS8. Both LMADS8/9 mRNAs were prevalent in the first and second whorl tepals during all stages of development and were expressed in the stamen only in young flower buds. LMADS8/9 could both form homodimers, but the ability of LMADS8 homodimers to bind to CArG1 was relatively stronger than that of LMADS9 homodimers. 35S:LMADS8 completely, and 35S:LMADS9 only partially, rescued the second whorl petal formation and partially converted the first whorl sepal into a petal-like structure in Arabidopsis pi-1 mutants. Ectopic expression of LMADS8-C (with deletion of the 29 amino acids of the C terminal sequence) or LMADS8-PI (with only the PI motif deleted) only partially rescued petal formation in pi mutants, which was similar to what was observed in 35S:LMADS9/pi plants. In contrast, 35:LMADS9+L8C (with the addition of the 29 amino acids of the LMADS8 C-terminal sequence) or 35S:LMADS9+L8PI (with the addition of the LMADS8 PI motif) demonstrated an increased ability to rescue petal formation in pi mutants, which was similar to what was observed in 35S:LMADS8/pi plants. Furthermore, ectopic expression of LMADS8-M (with the MADS domain truncated) generated more severe dominant negative phenotypes than those seen in 35S:LMADS9-M flowers. These results revealed that the 29 amino acids including the PI motif in the C-terminal region of the lily PI orthologue are valuable for its function in regulating perianth organ formation. PMID- 22068147 TI - Do viral infections mimic bacterial sepsis? The role of microvascular permeability: A review of mechanisms and methods. AB - A dysregulated immune response and functional immunosuppression have been considered the major mechanisms of the bacterial sepsis syndrome. More recently, the loss of endothelial barrier function and resultant microvascular leak have been found to be a key determinant of the pathogenesis of bacterial sepsis. Whether a similar paradigm applies to systemic viral syndromes is not known. Answering this question has far-reaching implications for the development of future anti-viral therapeutic strategies. In this review, we provide an overview of the structure and function of the endothelium and how its barrier integrity is compromised in bacterial sepsis. The various in vitro and in vivo methodologies available to investigate vascular leak are reviewed. Emphasis is placed on the advantages and limitations of cell culture techniques, which represent the most commonly used methods. Within this context, we appraise recent studies of three viruses - hantavirus, human herpes virus 8 and dengue virus - that suggest microvascular leak may play a role in the pathogenesis of these viral infections. We conclude with a discussion of how endothelial barrier breakdown may occur in other viral infections such as H5N1 avian influenza virus. PMID- 22068146 TI - Solanum lycopersicum cytokinin response factor (SlCRF) genes: characterization of CRF domain-containing ERF genes in tomato. AB - Cytokinin is an influential hormone in growth and developmental processes across many plant species. While several cytokinin-regulated genes have been well characterized in Arabidopsis, few have been identified in tomato, Solanum lycopersicum. Here a tomato family of 11 highly related cytokinin response factor genes designated as SlCRF1-SlCRF11 (Solanum lycopersicum cytokinin response factor) are identified and characterized. SlCRFs are AP2/ERF transcription factors and generally orthologous to Arabidopsis CRF clade members (AtCRFs). Some SlCRF genes lack a direct Arabidopsis orthologue and one SlCRF has a unique protein domain arrangement not seen in any other CRF protein. Expression analysis of SlCRF1-SlCRF11 revealed differential patterns and levels across plant tissues examined (leaf, stem, root and flower). Several SlCRFs show induction by cytokinin to various degrees, similar to AtCRFs. Additionally it is shown that some SlCRFs can be regulated by other factors, including NaCl, ethylene, methyl jasmonate, and salicylic acid. Examination of SlCRF proteins in transient Agrobacterium infiltration experiments indicates they can be nuclear localized in planta. Using a bimolecular fluorescence complementation (split-yellow fluorescent protein) system, it is also shown that SlCRF proteins can interact to form homo- and heterodimers. Overall this work indicates that some SlCRFs resemble previously identified CRFs in terms of structure, expression, and cytokinin regulation. However, SlCRFs have novel CRF protein forms and responses to abiotic factors, suggesting they may have a diverse set of roles in stress and hormone regulation in tomato. PMID- 22068148 TI - SP600125 inhibits Orthopoxviruses replication in a JNK1/2 -independent manner: Implication as a potential antipoxviral. AB - The pharmacological inhibitor SP600125 [anthra(1,9-cd)pyrazol-6(2H)-one 1,9 pyrazoloanthrone] has been largely employed as a c-JUN N-terminal kinase (JNK1/2) inhibitor. In this study, we evaluated whether pretreatment with SP600125 was able to prevent Orthopoxviruses Vaccinia virus (VACV), Cowpox virus (CPXV) and modified Vaccinia virus Ankara (MVA) replication. We found that incubation with SP600125 not only blocked virus-stimulated JNK phosphorylation, but also, significantly reduced virus production. We observed 1-3 log decline in viral yield depending on the cell line infected (A31, BSC-40 or BHK-21). The reduction in viral yield correlated with a dramatic impact on virus morphogenesis progress, intracellular mature viruses (IMV) were barely detected. Despite the fact that SP600125 can act as an efficient anti-orthopoxviral compound, we also provide evidence that this antiviral effect is not specifically exerted through JNK1/2 inhibition. This conclusion is supported by the fact that viral titers measured after infections of JNK1/2 knockout cells were not altered as compared to those of wild-type cells. In contrast, a decline in viral titers was verified when the infection of KO cells was carried out in the presence of the pharmacological inhibitor. SP600125 has been the focus of recent studies that have evaluated its action on diverse viral infections including DNA viruses. Our data support the notion that SP600125 can be regarded as a potential antipoxviral compound. PMID- 22068149 TI - Acute pharmacokinetics of memantine in the mouse. AB - The pharmacokinetics of memantine, a widely prescribed medication in the United States and the European Union for the treatment of moderate-to-severe Alzheimer's disease (AD), have not been well explored in the mouse. Memantine is a highly unspecific blocker of many channels and how memantine may be of benefit in AD remains a mystery. Therefore, the investigation of memantine in the mouse, the most commonly chosen subject for modeling AD, has strong potential to lead to better therapies. Here, we present an acute pharmacokinetic analysis of memantine in mouse brain tissue and blood serum for a variety of experimentally relevant doses. The data help shed light on the mechanism of memantine action in vivo, and demonstrate that subcutaneous doses above 10 mg/kg in the mouse are most likely not therapeutically relevant to the human. PMID- 22068150 TI - Physicochemical properties of imidazolium-derived ionic liquids with different C 2 substitutions. AB - Five room temperature ionic liquids based on C-2 substituted imidazolium cations and bis(trifluoromethanesulfonyl)imide (TFSI) anions were synthesized and their physicochemical properties: thermal property, density, viscosity, ionic conductivity, self-diffusion coefficients, and electrochemical stability, were systematically investigated. The temperature dependence of both viscosity and ionic conductivities of these ionic liquids can be described by the Vogel-Fulcher Tamman (VFT) equation. Compared with the reference, 1-propyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, the introduction of functional groups at the C-2 position generally increased the viscosity and lowered the ionic conductivity. The introduction of an ether group (-CH(2)OCH(2)CH(2)CH(2)CH(3)) at the C-2 position not only enhanced the reduction stability of the ionic liquids but also exhibited the lowest solid electrolyte interfacial resistance (R(SEI)). In contrast, the introduction of a cyano group (-CN) at the C-2 position not only decreased the reduction stability but also adversely increased the SEI resistance. The effect of the C-2 substitution on the reduction stability was explained by the change in the energy level of the lowest unoccupied molecular orbital. The self-diffusion coefficients (D) of each ion were measured by pulsed field gradient nuclear magnetic resonance (PFG-NMR). The lithium transference number (t(Li)) of 0.5 M LiTFSI/IL solutions calculated from the self-diffusion coefficients was in the range of 0.04 to 0.09. PMID- 22068151 TI - Dasatinib as salvage therapy for steroid refractory and imatinib resistant or intolerant sclerotic chronic graft-versus-host disease. AB - Sclerotic chronic graft-versus-host disease (scGVHD) is a severe form of this disease that resembles systemic sclerosis and has limited and disappointing treatment options. Tyrosine kinase inhibitors (TKI) targeting up-regulated profibrotic pathways, such as imatinib mesylate, have been proposed as a potential therapeutic approach for patients with scGVHD. Dasatinib, a second generation TKI with a well-established safety and efficacy profile in chronic myeloid leukemia patients, who are refractory or intolerant to imatinib, has also shown potent antifibrotic effects. We present here the first direct clinical evidence, from 3 patients treated in a small single-center series, suggesting that dasatinib can be a therapeutic option for patients with severe scGVHD resistant or intolerant to imatinib. All patients achieved partial response, with improvement in scGHVD target organs severity, joint mobility, lung impairment, and deep fibrotic lesions. This clinical response has remained stable or continued to improve after a median of 22 months (20-25) on dasatinib treatment, with very good tolerance. In addition, corticosteroids could be discontinued or significantly reduced in all patients. This clinical evidence suggests that dasatinib could be a safe and effective alternative for scGVHD patients refractory to corticosteroids and resistant or intolerant to imatinib. Based on these preliminary findings, and in order to address appropriate patient selection, time of intervention, and choice of drug, future larger studies should more formally establish the efficacy and safety of second-generation TKI for the treatment of scGVHD. PMID- 22068152 TI - Measurement of the proximity effect for indoor air pollutant sources in two homes. AB - Personal exposure to air pollutants can be substantially higher in close proximity to an active source due to non-instantaneous mixing of emissions. The research presented in this paper quantifies this proximity effect for a non buoyant source in 2 naturally ventilated homes in Northern California (CA), assessing its spatial and temporal variation and the influence of factors such as ventilation rate on its magnitude. To quantify how proximity to residential sources of indoor air pollutants affects human exposure, we performed 16 separate monitoring experiments in the living rooms of two detached single-family homes. CO (as a tracer gas) was released from a point source in the center of the room at a controlled emission rate for 5-12 h per experiment, while an array of 30-37 real-time monitors simultaneously measured CO concentrations with 15 s time resolution at radial distances ranging from 0.25-5 m under a range of ventilation conditions. Concentrations measured in close proximity (within 1 m) to the source were highly variable, with 5 min averages that typically varied by >100-fold. This variability was due to short-duration (<1 min) pollutant concentration peaks ("microplumes") that were frequently recorded in close proximity to the source. We decomposed the random microplume component from the total concentrations by subtracting predicted concentrations that assumed uniform, instantaneous mixing within the room and found that these microplumes can be modeled using a 3 parameter lognormal distribution. Average concentrations measured within 0.25 m of the source were 6-20 times as high as the predicted well-mixed concentrations. PMID- 22068153 TI - Children's Appraisals of their Experiences in Out-of-Home Care. AB - Few studies have asked children directly about their experiences in out-of-home care. This study uses data collected from 180 nine- to-11-year-old children currently in out-of-home care who were asked about their perceptions and appraisals of out-of-home care. Analysis of variance and chi-square analyses were used to examine whether children's appraisals of their lives following removal from their families of origin differ as a function of age, gender, race/ethnicity, type and severity of maltreatment, length of time in out-of-home care, placement type, attachment to current caregivers, and rating of current caregiver/home. Youth who were sexually and emotionally abused, youth who were satisfied with their current caregivers and placements, and girls were more likely to state that their lives would have been worse had they remained with their families of origin. Youth who were physically abused were more likely to report that their lives would have remained the same. Children living in group care were more likely than those living in family foster care or with kin to report that their lives would have been better had they remained with their families of origin. Differences were not found between children living in family foster care and those living with kin nor did children's appraisals differ based on age, race, ethnicity, length of time in out-of-home care, neglect, or severity of maltreatment. PMID- 22068154 TI - Crystal structure of NAD+-dependent Peptoniphilus asaccharolyticus glutamate dehydrogenase reveals determinants of cofactor specificity. AB - Glutamate dehydrogenases (EC 1.4.1.2-4) catalyse the oxidative deamination of l glutamate to alpha-ketoglutarate using NAD(P) as a cofactor. The bacterial enzymes are hexamers and each polypeptide consists of an N-terminal substrate binding (Domain I) followed by a C-terminal cofactor-binding segment (Domain II). The reaction takes place at the junction of the two domains, which move as rigid bodies and are presumed to narrow the cleft during catalysis. Distinct signature sequences in the nucleotide-binding domain have been linked to NAD(+) vs. NADP(+) specificity, but they are not unambiguous predictors of cofactor preferences. Here, we have determined the crystal structure of NAD(+)-specific Peptoniphilus asaccharolyticus glutamate dehydrogenase in the apo state. The poor quality of native crystals was resolved by derivatization with selenomethionine, and the structure was solved by single-wavelength anomalous diffraction methods. The structure reveals an open catalytic cleft in the absence of substrate and cofactor. Modeling of NAD(+) in Domain II suggests that a hydrophobic pocket and polar residues contribute to nucleotide specificity. Mutagenesis and isothermal titration calorimetry studies of a critical glutamate at the P7 position of the core fingerprint confirms its role in NAD(+) binding. Finally, the cofactor binding site is compared with bacterial and mammalian enzymes to understand how the amino acid sequences and three-dimensional structures may distinguish between NAD(+) vs. NADP(+) recognition. PMID- 22068155 TI - Metallothionein as a clonable high-density marker for cryo-electron microscopy. AB - Cryo-electron microscopy is expanding its scope from macromolecules towards much larger and more complex cellular specimens such as organelles, cells and entire tissues. While isolated macromolecular specimens are typically composed of only very few different components that may be recognized by their shape, size or state of polymerization, cellular specimens combine large numbers of proteinaceous structures as well as nucleic acids and lipid arrays. Consequently, an unambiguous identification of these structures within the context of a whole cell may create a very difficult challenge. On plastic-embedded specimens, or Tokuyasu sections (Tokuyasu, 1980), epitopes that are exposed at the surface can be tagged by antibodies. However, vitrified sections have to be kept at strict cryo-conditions (below -140 degrees C) and therefore do not allow any post sectioning treatment of the specimens other than data acquisition in the microscope. Hence, the labels have to be placed into the specimen before freezing. Here we report on the application of a small metal-clustering protein, metallothionein (MTH), as a clonable label capable of clustering metal atoms into a high-density particle with high spatial resolution. We tested MTH as a label for kinesin-decorated microtubules (MTs) as well as the building blocks of desmin intermediate filaments (IFs). PMID- 22068156 TI - Sargassumol, a novel antioxidant from the brown alga Sargassum micracanthum. PMID- 22068157 TI - Possible structural role of the disaccharide unit in Fe-bleomycin before and after oxygen activation. AB - Our previous investigation of the solution structure of Fe(II)-bleomycin pointed toward the carbamoyl group in the mannose moiety or a water molecule as possible alternative axial ligands to the metal center in this metallo-bleomycin. The possibility of a solvent molecule occupying the apical position trans to the primary amine has not been ruled out yet. In order to explore this possibility even further, the coordination chemistry of azide-bound Fe(II)-bleomycin was investigated with the use of NMR applied to paramagnetic molecules. Fe(II)- and apo-bleomycin were also re-visited. Comparison of the NMR results for both Fe(II) bound molecules obtained in the present study strongly suggests that the carbamoyl oxygen is ligated to Fe(II), and it is released from coordination upon azide binding. This event is suggested based on the diminished paramagnetic character exhibited by the carbohydrate moiety in Fe(II)-azide-bleomycin when compared with its parent metal complex. A possible structural role for the glucopyranose fragment, which changes throughout the process that starts with metallo-bleomycin formation and ends with DNA binding, is discussed. The study of the coordination of azide by Fe(II)-bleomycin through NMR has not been reported previously. Unlike magnetic CD data, NMR offers a residue-by-residue account of the possible structural changes that take place in Fe(II)-bleomycin after azide binding. PMID- 22068158 TI - Cytotoxic xanthone-anthraquinone heterodimers from an unidentified fungus of the order Hypocreales (MSX 17022). AB - Two new xanthone-anthraquinone heterodimers, acremoxanthone C (5) and acremoxanthone D (2), have been isolated from an extract of an unidentified fungus of the order Hypocreales (MSX 17022) by bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Two known related compounds, acremonidin A (4) and acremonidin C (3) were also isolated, as was a known benzophenone, moniliphenone (1). The structures of these isolates were determined via extensive use of spectroscopic and spectrometric tools in conjunction with comparisons to the literature. All compounds (1-5) were evaluated against a suite of biological assays, including those for cytotoxicity, inhibition of the 20S proteasome, mitochondrial transmembrane potential and nuclear factor-kappaB. PMID- 22068159 TI - The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis. AB - AIMS: The epidermal growth factor-like protein Delta-like 1 (DLK1) regulates multiple differentiation processes. It resembles NOTCH ligands structurally and is considered a non-canonical ligand. Given the crucial role of the NOTCH pathway in angiogenesis, we hypothesized that DLK1 could regulate angiogenesis by interfering with NOTCH. We therefore investigated the expression and function of DLK1 in the vascular endothelium and its role in the regulation of angiogenesis. METHODS AND RESULTS: We report DLK1 expression in the endothelium of different species, including human, cow, pig, and mouse. Angiogenesis was studied by using in vitro and in vivo models of angiotube formation in endothelial cells, retinal phenotypes in Dlk1-null mice, and vessel development in zebrafish. DLK1 overexpression strongly inhibited angiotube formation, whereas lung endothelial cells from Dlk1-null mice were highly angiogenic. In vivo studies demonstrated DLK1-mediated inhibition of neovessel formation and revealed an altered pattern of angiogenesis in the retinas of Dlk1-null mice. The expression of human DLK1 in zebrafish embryos severely altered the formation of intersegmental vessels, while knockdown of the orthologous gene was associated with ectopic and increased tumour-induced angiogenesis. NOTCH-dependent signalling as determined by gene expression reporters was inhibited by the presence of DLK1 in vascular endothelial cells. In contrast, Dlk1-null mice showed increased levels of NOTCH downstream targets, such as Snail and Slug. CONCLUSION: Our results unveil a novel inhibitory role for DLK1 in the regulation of angiogenesis, mediated by antagonism of the NOTCH pathway, and establish the basis for investigating its action in pathological settings. PMID- 22068160 TI - Roles of saturated vs. polyunsaturated fat in heart failure survival: not all fats are created equal. PMID- 22068161 TI - Treatment with selumetinib preserves cardiac function and improves survival in cardiomyopathy caused by mutation in the lamin A/C gene. AB - AIMS: Mutations in A-type nuclear lamins gene, LMNA, lead to a dilated cardiomyopathy. We have reported abnormal activation of the extracellular signal regulated kinase1/2 (ERK1/2) signalling in hearts from Lmna(H222P/H222P) mice, which develop dilated cardiomyopathy. We therefore determined whether an inhibitor of ERK1/2 signalling that has been investigated in clinical trials for cancer has the potential to be translated to humans with LMNA cardiomyopathy. METHODS AND RESULTS: To evaluate the relevance of this finding in mice to patients, we analysed the ERK1/2 signalling in heart tissue from human subjects with LMNA cardiomyopathy and showed that it was abnormally activated. To determine whether pharmacological inhibitors of the ERK1/2 signalling pathway could potentially be used to treat LMNA cardiomyopathy, we administered selumetinib to male Lmna(H222P/H222P) mice starting at 16 weeks of age, after they show signs of cardiac deterioration, up to 20 weeks of age. Selumetinib is an inhibitor of ERK1/2 signalling and has been given safely to human subjects in clinical trials for cancer. Systemic treatment with selumetinib inhibited cardiac ERK1/2 phosphorylation and blocked increased expression of RNAs encoding natriuretic peptide precursors and proteins involved in sarcomere architecture that occurred in placebo-treated mice. Echocardiography and histological analysis demonstrated that treatment increases cardiac fractional shortening, prevents myocardial fibrosis, and prolongs survival. Selumetinib treatment did not induce biochemical abnormalities suggestive of renal or hepatic toxicity. CONCLUSION: Our results suggest that selumetinib or other related inhibitors that have been safely administered to humans in clinical trials could potentially be used to treat LMNA cardiomyopathy. PMID- 22068163 TI - Hepatitis B virus strains of subgenotype A2 with an identical sequence spreading rapidly from the capital region to all over Japan in patients with acute hepatitis B. AB - OBJECTIVE: To examine recent trends of acute infection with hepatitis B virus (HBV) in Japan by nationwide surveillance and phylogenetic analyses. METHODS: During 1991 through 2009, a sentinel surveillance was conducted in 28 national hospitals in a prospective cohort study. Genotypes of HBV were determined in 547 patients with acute hepatitis B. Nucleotide sequences in the preS1/S2/S gene of genotype A and B isolates were determined for phylogenetic analyses. RESULTS: HBV genotype A was detected in 137 (25% (accompanied by genotype G in one)) patients, B in 48 (9%), C in 359 (66%), and other genotypes in the remaining three (0.5%). HBV persisted in five with genotype A including the one accompanied by genotype G; another was co-infected with HIV type 1. The genotype was A in 4.8% of patients during 1991-1996, 29.3% during 1997-2002, and 50.0% during 2003-2008 in the capital region, as against 6.5%, 8.5% and 33.1%, respectively, in other regions. Of the 114 genotype A isolates, 13 (11.4%) were subgenotype A1, and 101 (88.6%) were A2, whereas of the 43 genotype B isolates, 10 (23.3%) were subgenotype B1, 28 (65.1%) were B2, two (4.7%) were B3, and three (7.0%) were B4. Sequences of 65 (64%) isolates of A2 were identical, as were three (23%) of A1, and five (18%) of B2, but none of the B1, B3 and B4 isolates shared a sequence. CONCLUSIONS: Acute infection with HBV of genotype A, subgenotype A2 in particular, appear to be increasing, mainly through sexual contact, and spreading from the capital region to other regions in Japan nationwide. Infection persisted in 4% of the patients with genotype A, and HBV strains with an identical sequence prevailed in subgenotype A2 infections. This study indicates the need for universal vaccination of young people to prevent increases in HBV infection in Japan. PMID- 22068162 TI - Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism. AB - BACKGROUND AND OBJECTIVES: Cholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. The growth factor, progranulin, is overexpressed in a number of tumours. The study aims were to assess the expression of progranulin in cholangiocarcinoma and to determine its effects on tumour growth. METHODS: The expression and secretion of progranulin were evaluated in multiple cholangiocarcinoma cell lines and in clinical samples from patients with cholangiocarcinoma. The role of interleukin 6 (IL-6)-mediated signalling in the expression of progranulin was assessed using a combination of specific inhibitors and shRNA knockdown techniques. The effect of progranulin on proliferation and Akt activation and subsequent effects of FOXO1 phosphorylation were assessed in vitro. Progranulin knockdown cell lines were established, and the effects on cholangiocarcinoma growth were determined. RESULTS: Progranulin expression and secretion were upregulated in cholangiocarcinoma cell lines and tissue, which were in part via IL-6-mediated activation of the ERK1/2/RSK1/C/EBPbeta pathway. Blocking any of these signalling molecules, by either pharmacological inhibitors or shRNA, prevented the IL-6-dependent activation of progranulin expression. Treatment of cholangiocarcinoma cells with recombinant progranulin increased cell proliferation in vitro by a mechanism involving Akt phosphorylation leading to phosphorylation and nuclear extrusion of FOXO1. Knockdown of progranulin expression in cholangiocarcinoma cells decreased the expression of proliferating cellular nuclear antigen, a marker of proliferative capacity, and slowed tumour growth in vivo. CONCLUSIONS: Evidence is presented for a role for progranulin as a novel growth factor regulating cholangiocarcinoma growth. Specific targeting of progranulin may represent an alternative for the development of therapeutic strategies. PMID- 22068164 TI - Recombination of hepatitis B virus DNA in patients with HIV. AB - INTRODUCTION: Hepatitis B is a major cause of death in patients with HIV who usually receive drugs active against hepatitis B virus (HBV). The variability of HBV DNA over time has been little studied. Recombination between different HBV genotypes has been described in many cross-sectional studies, but the frequency of intergenotypic and intragenotypic recombinations in individual patients is unknown. METHODS: 32 HIV-positive and 11 HIV-negative patients who remained HBV viraemic despite antiviral therapy for at least 1 year were studied. Genotyping was based on line probe assays and genotype-specific PCR. The variability of HBV DNA over time was examined with restriction length and single-strand conformational polymorphism (RFLP-SSCP). HBV DNA sequences obtained by cloning a 2800 bp PCR fragment were analysed for phylogenetic parameters (diversity and selection pressure) and recombination was detected with RDP3 software. RESULTS: Large fragments of HBV DNA could be amplified at two different time points in 33 patients. Marked quasi-species modifications occurred in 14 patients. In seven of these patients and in one patient with no change detectable by RFLP-SSCP, the 2800 bp fragment was cloned at two time points at least. In four (57%) of these seven patients, various intergenotypic or intragenotypic recombination events were detected between subvariants present in the initial quasi-species. Recombinant fragments mostly harboured antiviral resistance determinants and reflected a large increase in diversity and in positive selection pressure on the entire HBV quasi-species. CONCLUSIONS: In coinfected patients, HBV DNA recombination events are frequent during antiviral therapy, corresponding to increased positive selection pressure on the HBV quasi-species and to conservation of antiviral resistance mutations. In this population and at the individual level, recombination is a significant source of HBV genetic variability. PMID- 22068165 TI - Mesenteric fat in Crohn's disease: the hot spot of inflammation? PMID- 22068166 TI - Detection of pancreatic cancer tumours and precursor lesions by cathepsin E activity in mouse models. AB - BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA. Surgical resection is the only effective treatment; however, only 20% of patients are candidates for surgery. The ability to detect early PDAC would increase the availability of surgery and improve patient survival. This study assessed the feasibility of using the enzymatic activity of cathepsin E (Cath E), a protease highly and specifically expressed in PDAC, as a novel biomarker for the detection of pancreas-bearing pancreatic intraepithelial neoplasia (PanIN) lesions and PDAC. METHODS: Pancreas from normal, chronic pancreatitis and PDAC patients was assessed for Cath E expression by quantitative real-time PCR and immunohistochemistry. Human PDAC xenografts and genetically engineered mouse models (GEMM) of PDAC were injected with a Cath E activity selective fluorescent probe and imaged using an optical imaging system. RESULTS: The specificity of Cath E expression in PDAC patients and GEMM of pancreatic cancer was confirmed by quantitative real-time PCR and immunohistochemistry. The novel probe for Cath E activity specifically detected PDAC in both human xenografts and GEMM in vivo. The Cath E sensitive probe was also able to detect pancreas with PanIN lesions in GEMM before tumour formation. CONCLUSIONS: The elevated Cath E expression in PanIN and pancreatic tumours allowed in-vivo detection of human PDAC xenografts and imaging of pancreas with PanIN and PDAC tumours in GEMM. Our results support the usefulness of Cath E activity as a potential molecular target for PDAC and early detection imaging. PMID- 22068167 TI - Anti-TNF antibody therapy in Crohn's disease: the risk of a switch. PMID- 22068168 TI - Flt3 ligand expands CD103+ dendritic cells and FoxP3+ T regulatory cells, and attenuates Crohn's-like murine ileitis. AB - BACKGROUND; Imprinting an effector or regulatory phenotype on naive T cells requires education at induction sites by dendritic cells (DC). Objectives To analyse the effect of inflammation on the frequency of mononuclear phagocytes (MP) and the effect of altering their frequency by administration of Flt3-L in chronic ileitis. METHODS: Using a tumour necrosis factor (TNF) driven model of ileitis (ie, TNFDeltaARE) that recapitulates many features of Crohn's disease (CD), dynamic changes in the frequency and functional state of MP within the inflamed ileum were assessed by flow cytometry, immunofluorescence and real-time reverse-transcription PCR and by generating CX(3)CR1 GFP-reporter TNFDeltaARE mice. The effect of Flt3-L supplementation on the severity of ileitis, and the frequency of CD103(+) DC and of FoxP3(+) regulatory T cells was also studied in TNFDeltaARE mice. RESULTS: CD11c(Hi)/MHCII(+) MP accumulated in inflamed ilea, predominantly mediated by expansion of the CX(3)CR1(+) MP subpopulation. This coincided with a decreased pro-regulatory CD103(+) DC. The phenotype of these MP was that of activated cells, as they expressed increased CD80 and CD86 on their surface. Flt3-ligand administration resulted in a preferential expansion of CD103(+) DC that attenuated the severity of ileitis in 20-week-old TNFDeltaARE mice, mediated by increased CD4(+)/CD25(+)/FoxP3(+) regulatory T cells. CONCLUSIONS: Results support a role for Flt3-L as a potential therapeutic agent in Crohn's-like ileitis. PMID- 22068169 TI - TNFalpha inhibitors restrict T cell activation and cycling via Notch-1 signalling in inflammatory bowel disease. AB - BACKGROUND: Tumour necrosis factor alpha (TNFalpha) inhibitors such as adalimumab and infliximab are frequently prescribed for inflammatory bowel disease (IBD). Despite the clinical success of TNFalpha inhibitors, their physiological mode of action is not fully understood. The aim of this study was to investigate the mode of action of anti-TNFalpha agents in IBD. METHODS: It was hypothesised that Notch mediates anti-TNFalpha action in T cells. A study was carried out to identify Notch-1 as a link by which anti-TNFalpha antibodies mediate their inhibitory functions. RESULTS: TNFalpha inhibitors induced T cell apoptosis, inhibited activation, reduced cytokine secretion and restricted cell cycling. TNFalpha blockade at several levels showed that TNFalpha is responsible for inducing apoptosis by anti-TNFalpha but not for cell cycle restriction. By linking Notch and TNFalpha it was shown that (1) Notch-1 mucosal expression differs in inflamed and non-inflamed mucosa and increases in response to anti-TNFalpha treatment; (2) Notch-1 function is regulated by TNFalpha inhibitors; (3) Notch-1 binds to TNFalpha; and (4) Notch-1 inhibition prevents anti-TNFalpha-induced T cell cycle arrest but not apoptosis. CONCLUSIONS: TNFalpha inhibitors potently inhibit T cell function. By demonstrating for the first time that Notch-1 mediates the inhibitory effects of adalimumab and infliximab on T cell cycling, this study reveals a new mode of action and also an underlying signalling pathway by which biological agents act in IBD. PMID- 22068171 TI - Occupational exposure to crack detection dye penetrants and the potential for bladder cancer. PMID- 22068170 TI - Progranulin and cholangiocarcinoma: another bad boy on the block! PMID- 22068172 TI - Increased alveolar nitric oxide and systemic inflammation markers in silica exposed workers. AB - BACKGROUND: Exposure to silica dust may cause inflammatory responses, primarily in the lungs, although systemic effects have also been reported. Alveolar inflammation can be demonstrated by increased alveolar concentration of nitric oxide (NO), but information on the effects of silica dust on exhaled NO is sparse. Inflammatory mediators including cytokines are known to take part in silica-induced processes, but the role of adipokines has not been studied previously. OBJECTIVES: The aim of the study was to investigate the pulmonary and systemic inflammatory responses to occupational exposure to silica dust. METHODS: The authors examined 94 silica-exposed workers and 35 healthy volunteers. The authors also measured alveolar NO concentration, bronchial NO flux and the plasma levels of proinflammatory cytokines, interleukin (IL)-6 and IL-8, and the adipokines, adipsin, leptin, adiponectin and resistin. RESULTS: After adjusting for age, body mass index and pack-years of tobacco smoking, silica exposure was associated with significantly higher levels of alveolar NO (p=0.001), indicating inflammatory effects of silica in the peripheral lung. In addition, increased plasma concentrations of IL-6, adiponectin, adipsin and resistin were significantly associated with silica exposure (p=0.002, p=0.034, p<0.001 and p=0.048, respectively). CONCLUSIONS: In conclusion, measurement of alveolar NO concentration and plasma cytokine and adipokine levels seems to offer a modern means to demonstrate the inflammatory effects of exposure to silica. These measures might be useful in finding subjects with a significant immune response to silica particles and thus at higher risk of developing silicosis or other immunological diseases associated with exposure to silica, but further research is needed. PMID- 22068173 TI - Cadmium exposure and cancer mortality in the Third National Health and Nutrition Examination Survey cohort. AB - OBJECTIVE: This study examined prospective data from the Third National Health and Nutrition Examination Survey (NHANES III) cohort to investigate the relationship between cadmium exposure and cancer mortality, and the specific cancers associated with cadmium exposure, in the general population. METHODS: Vital status and cause of death through 31 December 2006 were obtained by the National Center for Health Statistics for NHANES III participants. The cadmium concentration of spot urine samples was measured and corrected for urine creatinine (uCd). Weighted Cox proportional hazards regression with age as the time metric was applied to estimate sex-specific adjusted HRs (aHRs) of mortality associated with uCd for all cancers and the cancers responsible for the most deaths in the USA. Estimates were stratified by smoking history and adjusted for education, body mass index and race. RESULTS: uCd was associated with cancer mortality (aHR per twofold higher uCd (95% CI), men: 1.26 (1.07 to 1.48); women: 1.21 (1.04 to 1.42)). In men, mortality from lung cancer, pancreatic cancer and non-Hodgkin lymphoma was associated with uCd; an association with leukaemia mortality was suggested. In women, associations were suggested with mortality due to lung cancer, leukaemia, ovarian and uterine cancer, but evidence was weaker than in men. CONCLUSIONS: Cadmium appears to be associated with overall cancer mortality in men and women, but the specific cancers associated differ between men and women, suggesting avenues for future research. Limitations of the study include the possibility of uncontrolled confounding by cigarette smoking or other factors, and the limited number of deaths due to some cancers. PMID- 22068174 TI - Occupational exposures and risk of stomach cancer by histological type. AB - OBJECTIVE: To explore the relationship between stomach cancer (SC), by histological type, and occupations and occupational exposures. METHODS: The authors conducted a hospital-based case-control study in south-east Spain. Subjects were 399 incident histological confirmed SC cases (241 intestinal and 109 diffuse adenocarcinomas) and 455 controls frequency matched by sex, age and province of residence. Occupation was coded according to the Spanish National Classification of Occupations 1994. Occupational exposures were assessed by the FINJEM Job Exposure Matrix. ORs were estimated by unconditional logistic regression adjusting for matching variables and education, smoking, alcohol and diet. RESULTS: In men, statistically significant increased risk of the diffuse subtype was found for 'cooks' (OR 8.02), 'wood-processing-plant operators' (OR 8.13) and 'food and related products machine operators' (OR 5.40); for the intestinal subtype, a borderline association was found for 'miners and quarry workers' (OR men 4.22, 95% CI 0.80 to 22.14). Significant increased risk was observed between the diffuse subtype of SC and the highest level of exposure to 'pesticides' (OR(H) both sexes 10.39, 95% CI 2.51 to 43.02, p(trend)=0.02) and between the intestinal subtype and asbestos (OR(H) men 3.71, 95% CI 1.40 to 9.83, p(trend)=0.07). Restricted analyses of exposures of 15 years and longer showed significant associations between the diffuse subtype and the exposure to 'wood dust' (OR men 3.05). CONCLUSIONS: This study supports the relationship previously suggested between SC and occupational exposure to dusty and high temperature environments. Several occupations may also increase the risk of diffuse SC but not the intestinal subtype. PMID- 22068175 TI - Residual cellular proliferation on the internal limiting membrane in macular pucker surgery. AB - PURPOSE: To provide pathology data on the completeness of epiretinal membrane (ERM) removal with and without internal limiting membrane (ILM) peeling. METHODS: Twenty-two patients with idiopathic ERM formation underwent vitrectomy with ERM removal and subsequent staining of the vitreomacular interface with brilliant blue. If the ILM was still present after ERM removal, it was peeled off. Both ERM and ILM specimens were harvested in different containers and prepared for flat mount phase-contrast and interference microscopy, immunocytochemistry, and transmission electron microscopy. RESULTS: In 14 patients (64%), the ILM was still present at the macula after ERM removal. On average, 20% (range, 2-51%) of the total cell count was left behind at the ILM if the ERM was removed only. There were mainly glial cells on the ILM, and few hyalocytes. In nine eyes, the cells were forming cell clusters. In 8 patients (36%), both ERM and ILM were removed together. Electron microscopy showed cellular proliferation directly attached to the ILM in these eyes, whereas in the sequentially peeled group, there was collagen interposed between the ERM and the ILM. Surgical ERM removal resulted in splitting of the vitreous cortex in these eyes, leaving the ILM with residual cells behind. CONCLUSION: Simple ERM removal results in sufficient separation of fibrocellular tissue in one third of cases, only. In 2 of 3 patients with idiopathic ERM, the vitreous cortex splits when the ERM is removed, leaving an average of 20% of the total cell count behind on the ILM. As these cells are capable of proliferation and causing ERM recurrence, staining of the ILM with subsequent removal seems beneficial in macular pucker surgery. PMID- 22068176 TI - Interdental cleaning behaviour and its relationship with psychological constructs based on the transtheoretical model. AB - PURPOSE: The aim of this study was to test the applicability of the Transtheoretical Model (TTM) to gain an understanding of interdental cleaning behaviour change in senior high school students (12th grade) in Iran. MATERIALS AND METHODS: Multistage cluster sampling was employed to recruit 361 senior high school students from 8 schools in Yazd City, Iran. This cross-sectional study took place from November 2008 to March 2009. Appropriate instruments were used to identify the stages of interdental cleaning behaviour and psychological attributes, including interdental cleaning behaviour, decisional balance, and self-efficacy. The statistical analysis of the data included descriptive statistics, t-test and ANOVA. RESULTS: Of the 361 students, nearly 12.5% were in the maintenance stage, while 49.6% were in the pre-contemplation stage, with the rest distributed among the other stages of interdental cleaning behaviour change. There was a statistically significant difference in the stages of interdental cleaning behaviour change by gender. Self-efficacy and decisional balance differed significantly across the stages of interdental cleaning behaviour change. CONCLUSION: The TTM was found to be useful in determining the stages of interdental cleaning behaviour change among students. This study suggests the development of theory-based and empirically supported intervention strategies and programs to improve interdental cleaning behaviour with an emphasis on improving students' self-efficacy in this area. PMID- 22068178 TI - Do malocclusions affect the oral health-related quality of life? AB - PURPOSE: The aim of this study was to assess the relationship between untreated malocclusions and oral health-related quality of life (OHRQOL) in male adolescents of Mashad (Iran) high schools. MATERIALS AND METHODS: In this observational cross-sectional descriptive study, 120 male students were randomly selected among Mashad (Iran) high schools. These students filled out an oral health-related quality of life questionnaire (the modified version of CPQ), and then they were clinically examined to determine their malocclusions according to the Index of Complexity, Outcome and Need (ICON), and finally the relationship between these two variables was assessed with the Pearson correlation test. RESULTS: There was a statistically significant relationship between ICON scores and the quality of life levels (P < 0.01). The assessment of four sections of the questionnaire showed that among these four sections (oral symptoms, functional limitations, emotional well-being, social well-being), only oral symptoms were significantly correlated with the ICON score (P < 0.05). CONCLUSION: Malocclusion plays an important role in the oral health-related quality of life. However, the relationship between emotional well-being, social well-being and malocclusions was not as strong as in previous studies. PMID- 22068177 TI - Analysis of the effectiveness of different hygiene procedures used in dental prostheses. AB - PURPOSE: To compare the effectiveness of bacterial plaque removal of six denture hygiene procedures used by patients to clean their dentures. MATERIALS AND METHODS: Fifteen students randomly divided into groups G1, G2, G3, G4, G5 and G6 used maxillary intraoral appliances for 24 h without cleaning them. Afterwards, the appliances were submitted to the following procedures: P1: washing under running water for 20 s; P2 and P3: cleaning with alkaline peroxide (Corega Tabs(r)) for 5 and 30 min, respectively; P4: brushing with water and liquid soap for 40 s; P5: alkaline hypochlorite for 10 minutes; P6: home use chlorine solution (Q'boa(r) at 0.45% for 10 min), throughout a period of 6 consecutive weeks. The procedures followed a circulating scheme, so that all the appliances were submitted to all the hygiene methods studied. After the hygiene procedures, the appliances were stained, photographed and submitted to the weighing method. RESULTS: After ANOVA and Tukey's test, differences were observed: P5 = 0.73 +/- 0.3 (b), P6 = 1.27 +/- 0.4(b,c), P4 = 1.92 +/- 0.5 (b,c), P3 = 2.24 +/- 1.0 (b,c), P2 = 7.53 +/- 2.5 (c) and P1 = 26.86 +/- 15. 3 (a). CONCLUSION: From the results of the study, it could be concluded that the use of alkaline hypochlorite is the best way to remove bacterial plaque, followed by the home-use chlorine solution and brushing with water and liquid soap. Corega Tabs(r) must be used for 30 min of immersion to have a cleaning effectiveness similar to that of alkaline hypochlorite. PMID- 22068179 TI - Awareness and attitude of diabetic patients about their increased risk for oral diseases. AB - PURPOSE: To assess: 1) awareness of diabetic patients about their increased risk for oral diseases, 2) attitudes of diabetic patients towards maintaining good oral health through oral self-care and regular dental visits and 3) their sources of information on oral health. MATERIALS AND METHODS: A self-administered questionnaire was used to assess the main objectives of the study. Two hundred diabetic patients ranging in age from 17 to 78 years old participated in the study. RESULTS: A majority of the participants had type 2 diabetes. The awareness of diabetic patients of their increased risk for oral diseases is low compared to their awareness of systemic diseases. Their attitude towards maintaining good oral health is poor. Of the participants, only 17% brush their teeth twice daily, 61% never use dental floss, and 67% had not visited a dental clinic within the last year. Regarding participants' sources of awareness, 53% learned from a dentist and 30% through other media sources. A significant association (P < 0.05) was found between glycaemic control and oral infections and between duration of diabetes and denture problems. CONCLUSIONS: Diabetic patients were found to have little awareness of their increased risk for oral diseases. In order to promote proper oral health and to reduce the risk of oral diseases, health professionals in both the dental and medical fields need to develop programs to educate the public about the oral manifestations of diabetes and its complications for oral health. PMID- 22068180 TI - Addressing tobacco control in dental practice: a survey of dentists' knowledge, attitudes and behaviours in India. AB - PURPOSE: Dental professionals are strategically placed to be the leaders in tobacco prevention and cessation as they provide preventive and therapeutic services to a basically healthy population on a regular basis. The objective of this study was to assess the tobacco cessation knowledge, attitudes and behaviours of dental practitioners in Kochi (Cochin), Kerala, India. MATERIALS AND METHODS: A sampling frame of dentists enrolled in the Indian Dental Association (IDA), Kochi (Cochin) branch, practising in Ernakulam city, was obtained from the IDA. The letter describing the rationale for the study contained a 35-item pre-tested questionnaire and was personally delivered along with a stamped envelope. One hundred fourteen dentists returned a usable questionnaire. Data were entered and analysed using SPSS 12. Frequencies were calculated for all variables. RESULTS: Based on the responding dentists' self reports, 54.6% were not confident in tobacco cessation counselling, 10.6% never asked, 60.9% asked in 50% of their patients about tobacco use and 17.6% of the dentists surveyed were smokers themselves. Participating dentists perceived that they were interested in using tobacco cessation counselling, but were not sure of quitting rates in their patients. The average time spent counselling patients about tobacco cessation was less than 2 minutes. CONCLUSION: The dentists perceived that lack of formal training leads to less motivation about tobacco counselling and hence infrequently incorporated tobacco cessation into their dental practices. The cessation of tobacco habits among dentists is essential. PMID- 22068181 TI - Reproducibility of adjunct techniques for diagnosis of dental caries in an epidemiological situation. AB - PURPOSE: To evaluate the reproducibility of visual exams under natural light (VE1), visual exams under artificial light (VE2), radiographic bitewing exams (BW), fibre optic transillumination exams (FOTI) and DIAGNOdent exams (DD) in epidemiological settings. MATERIALS AND METHODS: Three examiners and one benchmark examiner examined thirteen 12-year-old schoolchildren under epidemiological conditions for the D3 (carious lesions in dentin) and D1+D3 (carious lesions in enamel or dentin) diagnostic criteria. RESULTS: The reproducibility (intra/interexaminer agreement) under both diagnostic criteria was 'almost perfect' for the exams VE1 (D3: kappaintra = 0.91/kappainter = 0.85; D1+D3: kappaintra = 0.89/kappainter = 0.84), VE2 (D3: kappaintra = 0.91/kappainter = 0.85; D1+D3: kappaintra = 0.88/kappainter = 0.83), BW (D3: kappaintra = 0.95/kappainter = 0.92; D1+D3: kappaintra = 0.99/kappainter = 0.90) and FOTI (D3: kappaintra = 0.97/kappainter = 0.93; D1+D3: kappaintra = 0.87/kappainter = 0.83) exams and 'fair' for the DD exam (D3: kappaintra = 0.36/kappainter = 0.35; D1+D3: kappaintra = 0.30/kappainter = 0.32). CONCLUSION: It was concluded that the VE1, VE2, BW, and FOTI exams presented good reproducibility under epidemiological conditions, and can be used accurately in epidemiological surveys. PMID- 22068182 TI - Comparative in vitro evaluation of efficacy of mouthrinses against Streptococcus mutans, Lactobacilli and Candida albicans. AB - PURPOSE: The present study was undertaken to compare the relative antimicrobial efficacy of two commercially available mouthrinses, Hexidine (0.12% chlorhexidine mouthrinse) and S-Flo (0.2% sodium fluoride), and a laboratory-manufactured propolis mouthrinse (10%) tincture with a dilution of 1:5 with water and their combinations against Streptococcus mutans, lactobacilli and Candida albicans. MATERIALS AND METHODS: Unstimulated saliva samples were obtained from the patients using the spitting method and the isolates of Streptococcus mutans, Lactobacillus and Candida albicans were obtained. The agar diffusion method was used to evaluate the antimicrobial activity of these test solutions and their combinations. RESULTS: Hexidine (0.12% chlorhexidine gluconate mouthrinse) showed the best antimicrobial efficacy against all the tested microorganisms. The laboratory manufactured propolis mouthrinse showed an effective antimicrobial action only against Streptococcus mutans. The antimicrobial efficacy of propolis (P) against Streptococcus mutans was similar to that of chlorhexidine (CHX) and the combination of propolis with chlorhexidine (CHX+P). S-Flo mouthrinse (0.2% sodium fluoride) showed the least efficacy against Streptococcus mutans among all tested solutions, but had better efficacy than propolis against lactobacilli and Candida albicans. The antimicrobial efficacy of the combination of chlorhexidine and fluoride mouthrinse and the combination of chlorhexidine and propolis mouthrinse was less than chlorhexidine mouthwash alone. Among all the tested combinations, the combination of fluoride and propolis showed the least efficacy against all the tested microorganisms. CONCLUSION: The results of the study indicate that 0.12% chlorhexidine gluconate mouthrinse (Hexidine) has the best anti-microbial efficacy against all the tested microorganisms, with laboratory manufactured propolis mouthrinse showing an equivalent efficacy against Streptococcus mutans only. No added advantage of using the tested mouthrinse combinations was observed. PMID- 22068183 TI - Effect of dentifrices against hydrochloric acid-induced erosion. AB - PURPOSE: This in vitro investigation assessed whether different dentifrices would be capable of controlling the enamel erosion progression caused by HCl. MATERIALS AND METHODS: Sixty bovine enamel slabs were covered with acid-resistant varnish, except for a 2.5-mm2 circular area on the labial surface. According to a complete block design, the experimental units were immersed in HCl solution (pH 1.2; 0.1M). After storage in artificial saliva for 1 h, specimens (n = 15) were exposed to different dentifrices: Sensodyne Cool Gel (1100 ppm F), Sensodyne ProNamel (1450 ppm F), and PrevDent 5000 (5000 ppm F). The control group was immersed in deionised water. Following five cycles of erosive challenge, the slabs were prepared for porosity evaluation using solutions of copper sulfate and rubeanic acid. RESULTS: ANOVA demonstrated no difference in the enamel porosity as a function of the dentifrice employed (P = 0.5494). CONCLUSION: The damage caused by a simulated intrinsic erosive challenge seems unable to be controlled by fluoridated dentifrices, even when this ion is found in elevated concentrations. PMID- 22068185 TI - Oral hygiene and periodontal status among detainees in a juvenile detention center, India. AB - PURPOSE: To assess the oral hygiene and periodontal status and analyse the influence of age, education, institutionalization, type of visit and oral health behaviour on oral hygiene and periodontal status among detainees in juvenile detention center in Udaipur city, Rajasthan, India. MATERIALS AND METHODS: The total sample comprised 223 subjects (67.7% male and 32.3% female) aged 6 to 18 years. Clinical examination included assessment of oral hygiene and periodontal status using OHI-S (Oral Hygiene Index-Simplified) and CPI (Community Periodontal Index), respectively. Analysis of variance (ANOVA), chi-square, Student t-test and stepwise multiple linear and multiple logistic regression analysis were carried out to find the relation between oral hygiene/ periodontal status and different independent variables. RESULTS: The results showed that the oral hygiene status of detainees was poor, with only 28.1% of the subjects having good oral hygiene. Mean OHI-S scores were significantly associated with all independent variables. Overall periodontal disease prevalence was 80.2% with bleeding and calculus contributing a major part (71.9%). Stepwise multiple linear and logistic regression analysis revealed that oral hygiene practice and type of visit in the detention center were the best predictors for the oral hygiene index, and for periodontal disease it was oral hygiene practice alone. CONCLUSION: The findings confirmed that detainees in the juvenile detention center have poor oral hygiene and an increased prevalence of periodontal disease compared to that of similarly ages in the general population. PMID- 22068184 TI - Plaque, gingival bleeding and calculus formation after supragingival scaling with and without polishing: a randomised clinical trial. AB - PURPOSE: The aim of this study was to compare the effect of polishing after scaling and root planing on supragingival plaque, calculus formation, and gingival bleeding. MATERIALS AND METHODS: The study was designed as a split-mouth randomised clinical trial. Seventy-six patients were submitted to supragingival scaling on the six mandibular anterior teeth with manual curettes until a smooth surface was achieved. Subsequently, quadrants were randomly selected to be polished (test) or not (control) with a rubber cup and pumice. One, two and three weeks following treatment, a blinded examiner evaluated the visible plaque index, gingival bleeding index and the presence of supragingival calculus on the lingual tooth surfaces. RESULTS: The results showed that unpolished surfaces exhibited higher mean percentages of visible plaque in the third week. No statistically significant differences were observed between unpolished and polished sites related to gingival bleeding. Calculus formation was higher on unpolished sites than on polished sites at 2 and 3 weeks. Dental polishing after supragingival scaling contributed to reducing plaque and calculus formation. CONCLUSIONS: Polishing exerts an inhibitory effect on plaque and calculus formation. PMID- 22068186 TI - Risk indicators for increased periodontal probing depth in subjects attending a public dental school in Brazil. AB - PURPOSE: To assess the prevalence, extent and severity of periodontal probing depth (PD) and their association with sociodemographic and behavioural parameters in subjects attending a public dental school in Brazil. MATERIALS AND METHODS: Five hundred and fifty-nine consenting participants (18 to 77 years of age) were submitted to full-mouth periodontal clinical examination and anamnesis questionnaires. The data were analysed by multivariable models using logistic regression analyses. The dependent variables were moderate (>= 5 mm in >= 10% of sites) and deep (>= 7 mm in at least one site) PD. RESULTS: The prevalence of individuals with at least one site with PD >= 5 mm or >= 7 mm was 69% and 54%, respectively. Mean PD ranged from 2.86 to 3.08 mm, and the mean frequency of sites with moderate and deep PD ranged from 10.74% to 14.99%, and from 4.60% to 5.36%, respectively, according to age. Multivariate analyses identified a higher risk for having PD >= 5 in >= 10% of sites and 7 mm in at least one site in smokers (odds ratio [OR] = 10.56 and 9.10, respectively), and the presence of >10% of sites with bleeding on probing (BOP) (OR = 6.37 to 20.91, and 6.94 to 26.19, respectively). Age 36 to 50 years (OR = 1.95) and >50 years (OR = 3.15), presence of >30% of sites with supragingival biofilm (SB) (OR = 2.80), and >= 4 missing teeth (OR = 2.26) were risk indicators for PD >= 7 mm in at least one site. CONCLUSION: This particular Brazilian population presented high prevalence and extent of increased periodontal probing depth. Age, smoking, BOP, SB, and tooth loss were risk indicators associated with probing depth in these individuals. PMID- 22068187 TI - Prevalence of traumatic dental injuries among 12- to 15-year-old schoolchildren in Ambala district, Haryana, India. AB - PURPOSE: To assess the prevalence of traumatic dental injuries (TDIs) among 12- to 15-year-old schoolchildren in the Ambala district of Haryana state, India. MATERIALS AND METHODS: A study was carried out on 963 schoolchildren of 15 government schools in the Ambala district. The examiner was calibrated and a pilot study was conducted. Maxillary as well as mandibular anterior teeth were taken into consideration to assess the traumatic dental injuries. The teeth involved, place of and reason for injury and other demographic details were recorded in a structured format. Data were analysed using SPSS version 13.0. RESULTS: Out of 963 subjects, 14.4% (139) had at least one tooth with TDI. Of these subjects, males and females accounted for 16.2% (77) and 12.7% (62), respectively. Permanent maxillary central incisors were the most commonly affected teeth. Enamel fracture was the most common (80% [111]) followed by enamel-dentin fracture (17.2% [24]). A higher number of children with incisal overjet greater than 3 mm had TDI than those with less than 3 mm, although this difference was not statistically significant. Subjects with Class III and Class II Div II malocclusion were more likely to have TDI, 16.2% and 17.7% respectively. Lip-closure incompetence was found to be more common in subjects having a TDI. Amongst the subjects having a TDI, only 83.4% (116) were aware of their injury, and falling was the reason most commonly reported. CONCLUSION: Traumatic dental injuries are highly prevalent among schoolchildren. Most of the TDIs involve only tooth enamel. Incompetent lip closure was significantly associated with TDIs and a fall was the major cause for TDIs in this age group. PMID- 22068188 TI - Exploring the synthetic potency of the first furanothioglycoligase through original remote activation. AB - Thioglycosidic bonds are of utmost importance in biomolecules as their incorporation led to more stable glycomimetics with potential drug activities. Until now only chemical methods were available for their incorporation into glycofuranosyl conjugates. Herein, we wish to describe the use of the first furanothioglycoligase for the preparation of a great variety of thioaryl derivatives with moderate to excellent yields. Of great interest, a stable 1 thioimidoyl arabinofuranose, classically used in chemical glycosylation, was able to efficiently act as a donor through an original enzymatic remote activation mechanism. Study of the chemical structure as well as the nucleophilicity of the thiol allowed us to optimize this biocatalyzed process. As a consequence, this mutated enzyme constitutes an original, mild and eco-friendly method of thioligation. PMID- 22068189 TI - New directions in pharmacy education. PMID- 22068190 TI - The rocky road to educational change: adopting the entry-level PharmD at Maryland, 1989-93. PMID- 22068191 TI - Pharmacist-provided immunization compensation and recognition: white paper summarizing APhA/AMCP stakeholder meeting. AB - OBJECTIVES: To identify the current challenges and opportunities in compensation and recognition for pharmacist-provided immunizations across the lifespan and to establish guiding principles for pharmacist-provided immunization compensation and recognition. DATA SOURCES: 22 stakeholders gathered on June 29, 2011, at the American Pharmacists Association (APhA) headquarters in Washington, DC, for a meeting on immunization compensation that was convened by APhA and the Academy of Managed Care Pharmacy. Participants included representatives from community pharmacy practices (chain, grocery, and independent), employers, national consumer health and advocacy organizations, national pharmacy and public health organizations, health plan representatives, pharmacy benefit managers, and health information technology, standards, and safety organizations. Key immunization leaders from TRICARE Management Activity, the Centers for Medicare & Medicaid Services, the National Vaccine Program Office of the Department of Health & Human Services, and the Centers for Disease Control and Prevention (CDC) also participated in the meeting. SUMMARY: The increased numbers of pharmacists providing vaccination services and the availability of pharmacist-provided immunizations to populations in need of vaccines has continued to increase. This has resulted in a rise in the percentage of patients who receive vaccines at pharmacies. Pharmacists are now working to lever-age their ability to identify people with key risk factors (e.g., diabetes, heart disease or previous myocardial infarction), encourage them to receive their CDC-recommended vaccinations, and administer the required vaccine. Challenges and opportunities in compensation and recognition for pharmacist-provided immunizations across the adult lifespan persist. Variability in state practice acts, reimbursement and compensation processes and systems, and mechanisms for documentation of vaccine services create substantial differences in how pharmacist-provided immunizations are delivered throughout the United States. CONCLUSION: Pharmacist-provided immunizations are clinically sound, are cost effective, are readily accessible, and support our nation's public health goals. Pharmacists have demonstrated that patient vaccination rates have improved through expansion of pharmacist-provided immunizations. The profession should continue efforts to collaborate with other immunization stakeholders and expand a pharmacist scope of practice that is built around a uniform and recognized standard of immunization provision and that supports the provision of all CDC-recommended vaccines through pharmacy-provided immunizations. PMID- 22068192 TI - Impact of health screening and education on knowledge of coronary heart disease risk factors. AB - OBJECTIVES: To evaluate the effects of a community health screening and education intervention on knowledge of coronary heart disease (CHD) risk factors and participation in health-promoting behaviors. DESIGN: Descriptive, exploratory, nonexperimental study. SETTING: Little Rock, AR, from July 2007 to December 2007. PARTICIPANTS: 56 participants recruited from two community health screenings. INTERVENTION: Prescreening written questionnaire to determine baseline knowledge of CHD risk factors. Participants underwent risk factor screening (lipid profile, blood glucose, body mass index [BMI], and blood pressure) and received tailored education. A postscreening telephone questionnaire was administered 4 to 8 weeks later. MAIN OUTCOME MEASURES: Participant knowledge of CHD risk factors and participation in health-promoting behaviors pre- and postscreening. RESULTS: Of the 56 participants enrolled, 45 (80.4%) completed the postscreening telephone survey. Compared with prescreening responses, participants showed significantly greater postscreening knowledge of healthy values for CHD risk factors, including blood pressure (P = 0.02), fasting blood glucose (P = 0.03), fasting total cholesterol (P < 0.01), and BMI (P < 0.01). Following the screening, 20 (44.4%) participants had consulted their primary care provider and 31 (68.8%) made at least one healthy behavior change. Approximately one-half of participants reported changing eating habits, and 5 (11.1%) reported increased exercise. CONCLUSION: These results demonstrate that community-based health screening and education interventions can effectively promote public health knowledge and empower participants to engage in health-promoting behaviors. PMID- 22068193 TI - Lifestyle changes for prehypertension with other cardiovascular risk factors: findings from Thailand. AB - OBJECTIVE: To evaluate a model for community pharmacists to screen and recommend lifestyle changes for patients with prehypertension/hypertension and other elevated modifiable cardiovascular risk factors. DESIGN: Descriptive, exploratory, nonexperimental study. SETTING: One accredited community pharmacy in Hat Yai, Thailand, between October 2008 and January 2009. PARTICIPANTS: Individuals 35 years or older without any previous diagnosis of hypertension and other cardiovascular disease. INTERVENTION: Measurement of blood pressure, blood glucose, total cholesterol, and body mass index; history taking for smoking and physical exercise; laboratory referral; assessment of readiness to adopt lifestyle changes; and provision of verbal advice and an education pamphlet on cardiovascular risk factors and recommended lifestyle modifications. MAIN OUTCOME MEASURES: Number of prehypertensive/hypertensive participants, patient return rate at 3-month follow-up, rate of laboratory referral uptake, confirmed glucose intolerance and dyslipidemia, and changes from baseline in blood pressure level. RESULTS: 263 of 400 people eligible for screening were found to have prehypertension or hypertension. Of these patients, 57% returned at 3-month follow-up. Mean (+/-SE) systolic (6.5 +/- 0.89 mm Hg [95% CI 4.7-8.2], P < 0.001) and diastolic (2.2 +/- 0.82 [0.54-3.77], P = 0.009) blood pressure were lowered. Compared with baseline (39.3%), the percentage of normotensive participants increased significantly at 3-month follow-up (51.8%; P < 0.001). The overall laboratory referral uptake was 36% (50 of 138). Glucose intolerance was confirmed in 2 of 21 participants. Of the 42 patients accepting laboratory confirmation, total and low-density lipoprotein cholesterol were confirmed to be above the normal range in 100% and 78.6%, respectively. Among these participants, those who returned at follow-up were rescreened for blood glucose and total cholesterol. Both values were found to be in the normal range. Although more participants reported lifestyle changes at 3 months, the smoking rate and amount of physical exercise were not changed. CONCLUSION: Community pharmacists, through the use of point-of-care testing and referrals for laboratory testing, can detect patients who are at risk of developing or already have hypertension, diabetes, and/or dyslipidemia. Lifestyle advice from pharmacists can have a positive effect on these risk factors. PMID- 22068194 TI - Independent community pharmacist interest in participating in community pharmacy research networks. AB - OBJECTIVES: To assess the interest of American Pharmacy Services Corporation (APSC) independent community pharmacists in participating in a community pharmacy research network (CPRN) and to identify perceived barriers to participation in a CPRN. DESIGN: Descriptive, exploratory, nonexperimental study. SETTING: University of Kentucky and APSC during 2009-10. PARTICIPANTS: 65 APSC independent community pharmacists in Kentucky. INTERVENTION: Single-mode survey. MAIN OUTCOME MEASURE: Independent community pharmacists' willingness to participate in community-based research and perceived barriers to participation. RESULTS: A total of 65 independent community pharmacists from 191 pharmacies returned the survey. The majority of independent community pharmacists were "interested" or "very interested" (83.8%) in participating in a CPRN. Respondents were willing to participate for a mean (+/-SD) of 6.5 +/- 5.8 hours per week. However, they reported only being able participate in a CPRN for 5.2 +/- 4.1 hours per week, with time being the greatest limitation to participation. An overwhelming percentage of respondents (92.1%) were interested in learning more about opportunities to participate in a CPRN in the future. CONCLUSION: CPRNs are an emerging interest in community pharmacy practice. A CPRN is an opportunity for independent community pharmacies to collaborate and use resources as a group to conduct research to solve issues in the community pharmacy setting. PMID- 22068195 TI - Determining the gluten content of nonprescription drugs: information for patients with celiac disease. AB - OBJECTIVES: To determine whether the information on the gluten content of nonprescription drugs is readily available from the manufacturer/supplier, to identify how patients are directed on the product labeling to obtain answers to questions that they have about the nonprescription medication, and to determine the time needed to obtain information about the gluten content of the product when contacting manufacturers/suppliers. DESIGN: Descriptive, exploratory, nonexperimental study. SETTING: United States during July 2010. PARTICIPANTS: Manufacturers/suppliers of 41 nonprescription drug products. INTERVENTION: The packaging of the products was reviewed for information on gluten content. The manufacturer/supplier listed on each product's packaging was contacted using the phone number provided and questioned about the gluten content of the product. A uniform script was used for the telephone inquiry. The responses provided and the duration of the phone calls were documented. The manufacturer's websites also were reviewed for pertinent information. MAIN OUTCOME MEASURES: Gluten status of products, time spent on phone to determine gluten status, and availability of online information regarding gluten status. RESULTS: Information concerning the gluten content was not included on any of the products' packaging. The mean time required to receive a response was 6.2 minutes (median 5 minutes). A total of 15 products were reported to be gluten free; 13 products were not tested, but the manufacturer/supplier stated that they did not add gluten to the products; 9 products did not have any gluten added by the manufacturer/ supplier, but no guarantee was made that the raw ingredients were gluten free; 2 products contained gluten; and 2 products had no available gluten status information. Gluten information was found on product websites for a total of six products. Four of those six websites indicated gluten status that was different from the information provided via the telephone call with the manufacturer. CONCLUSION: Information concerning the gluten content of many nonprescription drugs is relatively easy for patients to obtain if the manufacturer/supplier is contacted. Although the time to obtain a response was quite short for many of the inquiries, it took a substantial amount of time to receive the requested information from some of the companies. PMID- 22068196 TI - Does bargaining affect Medicare prescription drug plan reimbursements to independent pharmacies? AB - OBJECTIVE: To examine how pharmacy bargaining activities affect reimbursement rates in Medicare Part D prescription drug plan (PDP) contracts, controlling for pharmacy quality attributes, market structures, and area socioeconomic status. DESIGN: Cross-sectional study. SETTING: Six Medicare regions throughout the United States between October and December 2009. PARTICIPANTS: Random sample of 1,650 independent pharmacies; 321 returned surveys containing sufficient responses for analysis. INTERVENTION: Pharmacies were surveyed regarding PDP reimbursement rates, costs, and cash prices of two popular prescription drugs (atorvastatin calcium [Lipitor-Pfizer] and lisinopril, 1-month supply of a common strength), as well as pharmacy bargaining activities and quality attributes. Data also were used from the National Council for Prescription Drug Programs pharmacy database, the 2000 U. S. Census, and the 2006 Economic Census on local market structures and area socio-economic status. MAIN OUTCOME MEASURE: PDP reimbursement rates. RESULTS: For the brand-name drug atorvastatin calcium, the PDP reimbursement was positively related to a pharmacy's request for a contract change (beta = 0.887, P < 0.05), whereas other bargaining activities were not significantly related to PDP reimbursement. However, for the generic drug lisinopril, no bargaining activities were found to be significantly related to the PDP reimbursement. CONCLUSION: Pharmacy request for a contract change was associated with higher reimbursement rates for the brand-name drug atorvastatin calcium in PDP contracts, after controlling for pharmacy quality attributes, local market structures, and area socioeconomic status; this finding likely applies to other brand-name drugs because of the structure of the contracts. Our results suggest that independent pharmacies are more likely to acquire higher reimbursement rates by engaging in active bargaining with third-party payers. PMID- 22068197 TI - Pharmacists' strategies for promoting medication adherence among patients with HIV. AB - OBJECTIVES: To provide pharmacists' perspectives on medication adherence barriers for patients with human immunodeficiency virus (HIV) and to describe pharmacists' strategies for promoting adherence to antiretroviral medications. DESIGN: Multisite, qualitative, descriptive study. SETTING: Four midwestern U. S. states, from August through October 2009. PARTICIPANTS: 19 pharmacists at 10 pharmacies providing services to patients with HIV. INTERVENTION: Pharmacists were interviewed using a semistructured interview guide. MAIN OUTCOME MEASURES: Barriers to medication adherence, pharmacist interventions, challenges to promoting adherence. RESULTS: Pharmacists reported a range of adherence barriers that were patient specific (e.g., cognitive factors, lack of social support), therapy related (e.g., adverse effects, intolerable medications), and structural level (e.g., strained provider relationships). They used a combination of individually tailored, patient-specific interventions that identified and resolved adherence barriers and actively anticipated and addressed potential adherence barriers. Pharmacist interventions included medication-specific education to enhance patient self-efficacy, follow-up calls to monitor adherence, practical and social support to motivate adherence, and patient referrals to other health care providers. However, the pharmacists faced internal (e.g., lack of time, lack of trained personnel) and external (e.g., insurance policies that disallowed patient enrollment in automatic prescription refill program) challenges. CONCLUSION: Pharmacists in community settings went beyond prescription drug counseling mandated by law to provide additional pharmacy services that were tailored to the needs of patients with HIV. Given that many individuals with HIV are living longer, more research is needed on the effectiveness and cost effectiveness of pharmacists' interventions in clinical practice, in order to inform insurance reimbursement policies. PMID- 22068198 TI - Emergency contraception counseling: an opportunity for pharmacists. AB - OBJECTIVE: To determine the impact of pharmacist counseling on patients' knowledge of emergency contraception (EC). DESIGN: Single-group, repeated measures analysis. SETTING: Academic medical center women's clinic in Little Rock, AR, between January and July 2010. PARTICIPANTS: 116 women 18 years or older. INTERVENTION: 10-minute education session provided by a pharmacist or trained student pharmacist. MAIN OUTCOME MEASURES: Change in participants' test scores (range 0 [lowest possible] to 13 [highest possible]) at three assessment periods (pretest, posttest, and follow-up) using 12 knowledge questions. RESULTS: 116 participants with a mean (+/-SD) age of 25 +/- 5.9 years participated in this study. Mean knowledge scores were 5.3 +/- 4.1 for the pretest and 10.7 +/- 1.4 for the posttest (P < 0.001). The least-squares mean EC knowledge test score (adjusted for demographics) was 5.86 at pretest, 10.75 at posttest, and 10.75 at follow-up. A nonsignificant small change in scores from posttest to follow-up was detected after the Tukey-Kramer adjustment. A higher education level was associated with higher knowledge scores in this population. CONCLUSION: Brief pharmacist-driven counseling sessions provided in a clinic setting are feasible and have a positive impact on immediate EC knowledge and long-term knowledge retention. PMID- 22068199 TI - Student pharmacist perspectives on providing pharmacy-access hormonal contraception services. AB - OBJECTIVE: To assess student pharmacists' interest and opinions in providing reproductive health services, particularly hormonal contraception (HC), in their future practices. METHODS: This descriptive, nonexperimental, cross-sectional study was conducted in California between February and May 2007. Surveys were distributed to 790 second- and third-year student pharmacists to measure interest, opinions, and perceived barriers in providing HC services. RESULTS: 502 survey responses (63.5% response rate) were received. Student pharmacists reported interest in providing HC services (96.2%) to both minors and adults (53.3%), adults (40.6%), or minors (6.2%). Students felt that patients would benefit from improved access and advice (94.0%). Inadequate pharmacist time was deemed an extremely important barrier in determining whether pharmacists could efficiently and effectively provide HC services, followed by lack of private counseling area in the pharmacy, inadequate patient health information, and lack of appropriate incentive structure. Students were interested in providing other reproductive health services, specifically preventive measures against sexually transmitted infections (STIs; 89.2%) and STI treatment for the partners of patients presenting with valid STI prescriptions (88.4%). CONCLUSION: Student pharmacists were very interested in providing pharmacy access to HC and related reproductive health services as future practitioners. The willingness of student pharmacists to provide this support indicates that pharmacy access to HC could be a viable service. PMID- 22068201 TI - Journal of the American Pharmaceutical Association (1961-1977) and American Pharmacy (1978-1995). PMID- 22068200 TI - Challenges of a pharmacist-directed peer support program among adolescents with diabetes. AB - OBJECTIVE: To describe the development and challenges of a pharmacist-directed peer support program among adolescents with diabetes. PRACTICE DESCRIPTION: The program was designed as adjunctive therapy for adolescents receiving care at the Diabetes Education and Research Center (DERC). DERC is an interdisciplinary facility at which the clinical pharmacist provides direct, diabetes-related patient care services. Through collaboration with DERC, pharmacists developed and facilitated each component of the program. PRACTICE INNOVATION: The U. S. Diabetes Conversation Map program was used for the educational component of the program. This is an innovative, American Diabetes Association-approved tool for providing group education on diabetes self-management. As trained facilitators of the conversation maps, the investigators educated group leaders on how to be facilitators for their peers. MAIN OUTCOME MEASURES: Glycosylated hemoglobin (A1C), diabetes self-management skills, and diabetes-related quality of life were measured at baseline and following program completion. Qualitative outcomes were measured via validated questionnaires in adolescents with type 1 diabetes. The investigators facilitated the gathering of all quantitative and qualitative data. RESULTS: Several participants did not meet all inclusion criteria; therefore, data from only six participants were assessed. A1C increased among participants, affirming the challenge of metabolic control during adolescence. Despite this, qualitative analysis of questionnaires revealed improvements in adherence to lifestyle modifications and health perception after program completion. CONCLUSION: Evidence illustrates beneficial effects of peer-facilitated support on the physical and psychological challenges of diabetes self-management; however, challenges existed when implementing this program among adolescents. Suggestions to overcome these challenges include same-sex support groups, use of an appealing setting for participants, incorporation into camps or after-school programs, and extended program length. Pharmacists are well equipped to assist individuals in comprehensive diabetes management programs such as the one described here because of their education and training in medication management, therapeutic lifestyle changes, and patient communication. PMID- 22068202 TI - Choosing between live attenuated and trivalent inactivated influenza vaccines for healthy children. PMID- 22068203 TI - Rivaroxaban, ticagrelor, and fidaxomicin. PMID- 22068204 TI - Improving severe sepsis outcomes, managing cholesterol in patients with diabetes, and pediatric adverse events. PMID- 22068206 TI - Limited influence of aspirin intake on mast cell activation in patients with food dependent exercise-induced anaphylaxis: comparison using skin prick and histamine release tests. AB - Food-dependent exercise-induced anaphylaxis (FDEIA) is a severe systemic syndrome induced by physical exercise after ingesting causative food. Aspirin is a well known trigger for anaphylaxis in patients with FDEIA. Possible mechanisms by which symptoms are aggravated by aspirin include enhanced antigen absorption and mast cell activation. The aim of this study was to determine whether aspirin intake has an influence on mast cell/basophil activation in patients with FDEIA. Provocation tests revealed that adding aspirin to the causative food challenge in 7 of 9 (77.8%) patients with FDEIA provoked symptoms. In most cases, pretreatment with aspirin did not enhance skin tests (71.4%) or histamine release tests (88.9%) with food allergen challenges. The study confirms that histamine release and skin prick tests can be adjunctive tools for diagnosing FDEIA. In addition, our results suggest that exacerbation of FDEIA symptoms by aspirin is not mediated by direct effects of aspirin on mast cell/basophil activation. PMID- 22068207 TI - Locking plates in osteoporosis: a biomechanical cadaveric study of diaphyseal humerus fractures. AB - OBJECTIVE: To determine whether locking plates offer an advantage in fixation of fractures in osteoporotic humeral bone. DESIGN: Biomechanical testing of 18 matched pairs of osteoporotic human cadaver humeri plated posteriorly with either all locked or all nonlocked screws. An established protocol was used to test the constructs with torque applied to a peak of +/-10 Nm for 1000 cycles at 0.3 Hz or until failure. Eighteen pairs were tested for failure, 11 pairs were tested for cycles survived, and 10 pairs were tested for stiffness. SETTING: University biomechanical laboratory. MAIN OUTCOME MEASUREMENTS: Percentage surviving testing, mean cycles survived, and stiffness. RESULTS: We observed catastrophic failure of the constructs in 47% of the samples. Humeri plated with nonlocking plates failed at a higher rate than those with locking plates (67% nonlocking vs 28% locking, n = 18 pairs, P = 0.008). Locking constructs also outperformed nonlocking constructs in mean cycles survived (707 cycles locking, 345 cycles nonlocking, n = 11 pairs, P < 0.05) and stiffness at 10 cycles (0.853 Nm/degree locking vs 0.416 Nm/degree nonlocking, n = 10 pairs, P < 0.001). CONCLUSIONS: Locking plates were shown to provide improved mechanical performance over nonlocking plates in torsional cyclic loading in a osteoporotic cadaveric fracture model. Our results confirm general conclusions of previous work that used a synthetic bone model of osteoporosis, but we found a high rate of catastrophic failure, questioning the validity of the previously published synthetic model of osteoporosis (overdrilling of synthetic bone) for this application. PMID- 22068208 TI - Anterior knee pain after tibial intramedullary nailing using a medial paratendinous approach. AB - OBJECTIVES: To determine the incidence, severity, and etiology of anterior knee pain after tibial intramedullary (IM) nailing using a medial paratendinous approach and to investigate the association between anterior knee pain and functional impairment. DESIGN: Retrospective study with current clinical and radiographic assessments. SETTING: Level I trauma center. PATIENTS: Forty-five patients with unilateral, tibial diaphyseal fractures treated with tibial IM nailing between August 2005 and January 2009. The mean follow-up was 22.3 months (range, 12-52 months). INTERVENTION: All patients underwent tibial IM nailing using a medial paratendinous approach. MAIN OUTCOME MEASUREMENTS: Anterior knee pain based on a visual analog scale and functional outcomes based on the Tegner activity score and the modified Lysholm score. RESULTS: Of the 45 patients, 16 (36%) were painless (N group), 16 (36%) had mild pain (M group), and 13 (28%) had moderate to severe pain (MS group). No group differences were found with respect to age, sex, body mass index, mode of injury, or type of fracture. With regard to nail prominence, superior nail prominence was greater in the MS group than in the other two groups (P = 0.042). There were no significant differences among the three groups in terms of anterior nail prominence (P = 0.221). The nail-apex distance in the MS group was significantly greater than in the other two groups (P = 0.033), and no significant difference was found between the N and M groups. The descending order of the activities with respect to severity of knee pain was kneeling, squatting, running, and stair ascending. Visual analog scale analysis revealed that the MS group had significantly more severe pain for all eight activities examined than the M group. At latest follow-up, the Tegner activity score was significantly lower in the MS group than in the other two groups (P = 0.008), and there were statistically significant intergroup differences in the modified Lysholm score (P < 0.001). CONCLUSION: Anterior knee pain after tibial IM nailing using a medial paratendinous approach was a frequent complication that was not uncommonly moderate to severe (28%) in Asian patients. Although the etiology of anterior knee pain is undoubtedly multifactorial, it may be related to nail prominence. Furthermore, the severity of anterior knee pain was significantly associated with functional outcome. LEVEL OF EVIDENCE: Therapeutic Level IV. See page 128 for a complete description of levels of evidence. PMID- 22068209 TI - Multifunctional nanoprobes for pathogen-selective capture and detection. AB - The synthesis of magnetic and fluorescent particles is described. The particles are biofunctionalized by binding pathogen-specific proteins to the particles via interactions between His-tags of proteins and zinc of the quantum dots. Detection of Salmonella and Staphylococcus aureus (S. aureus) by these particles is demonstrated. PMID- 22068210 TI - Examining clinically relevant levels of depressive symptoms in mothers following a diagnosis of epilepsy in their children: a prospective analysis. AB - OBJECTIVES: The objectives were to (1) document the risk of clinical depression in mothers in the 24 months after epilepsy diagnosis in their children, (2) determine whether the probability of risk of clinical depression changes over time, and (3) identify factors predictive of risk of clinical depression. METHODS: Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study, a national prospective study of children 4-12 years old with new-onset epilepsy followed for 24 months. Risk-free survival was calculated using the life table approach. Binary sequence modeling for longitudinal data was implemented to identify risk factors. RESULTS: A total of 210 mothers were included in the analysis. Twenty-eight percent of mothers without clinically relevant levels of depressive symptoms at baseline were at risk for clinical depression by 24 months. The probability for risk of clinical depression and associated 95% confidence intervals by 6, 12, and 24 months was 0.13 (0.08, 0.18), 0.12 (0.07, 0.17), and 0.19 (0.10, 0.27), respectively. Significant predictors (p < 0.01) of risk of clinical depression during follow-up quantified using odds ratios (OR) were maternal age (OR = 0.94), number of anti-epileptic drugs child was prescribed (OR = 1.41), family functioning (OR = 0.83), family resources (OR = 0.93), and family demands (OR = 1.10). CONCLUSIONS: Risk of clinical depression in mothers after their child is diagnosed with epilepsy is common and relatively stable over time. Modifiable risk factors may present avenues for intervention to improve the mental health of mothers of children with epilepsy. PMID- 22068211 TI - Shift climate profiles and correlates in acute psychiatric inpatient units. AB - PURPOSE: Inpatient psychiatric units are dynamic in nature, potentially creating a different treatment experience for each person, which may be difficult to quantify. Among the goals of this multi-centre service evaluation project was an assessment of shift-to-shift changes in unit-level events and their impact on the social-emotional environment. METHODS: Over 1 year, various nurse-completed logs were used within the 11 participating Australian psychiatric units (n = 5,546 admissions) to record patient- and unit-level events per shift, including ratings of the overall social-emotional climate using a novel shift climate ratings (SCR) scale (n = 8,176 shifts). These were combined with admission-level patient characteristics to investigate shift climate profiles and correlates. RESULTS: Occupancy rates averaged 88% and two-thirds of admissions were involuntary. The psychometric performance of the SCR scale was considered to be satisfactory (e.g., high internal consistency, unidimensional factor structure, and evidence of discriminant and predictive validity). A series of hierarchical regressions revealed considerable variation in SCR total scores, with poorer climates being significantly associated with: day/afternoon shifts; higher occupancy levels; higher proportions of experienced staff, and male, older, or involuntary patients; higher rates of less serious aggressive incidents; reporting of additional staffing demands; and unit location in a stand-alone psychiatric hospital. CONCLUSIONS: The day-to-day social-emotional climate can have important consequences for patient engagement and recovery. Improved understanding of the role played by unit, staff and patient characteristics, together with routine monitoring, should facilitate the development and evaluation of targeted interventions to reduce adverse incidents and improve the overall social emotional climate. PMID- 22068216 TI - Molecular characterization of Hepatozoon canis in dogs from Colombia. AB - Hepatozoonosis is a tick-borne disease whose transmission to dogs occurs by ingestion of oocysts infected ticks or feeding on preys infested by infected ticks. Until now, there is no previous report of molecular characterization of Hepatozoon sp. in dogs from Colombia. EDTA blood samples were collected from 91 dogs from central-western region of Colombia (Bogota, Bucaramanga, and Villavicencio cities) and submitted to 18S rRNA Hepatozoon sp. PCR and blood smears confection. Phylogenetic analysis was used to access the identity of Hepatozoon species found in sampled dogs. From 91 sampled dogs, 29 (31.8%) were positive to Hepatozoon sp. (25 dogs were only positive in PCR, 1 was positive only in blood smears, and 3 were positive in both blood smears and PCR). After sequencing, the found Hepatozoon sp. DNA showed 100% of identity with Hepatozoon canis DNA isolates. The phylogenetic tree supported the identity of the found Hepatozoon sp. DNA, showing that the isolates from Colombia were placed in the same clade than other H. canis isolates from Venezuela, Spain, and Taiwan. This is the first molecular detection of H. canis in dogs from Colombia. PMID- 22068217 TI - The efficacy of antioxidants in functional recovery of spinal cord injured rats: an experimental study. AB - A total of 30 female Sprague-Dawley rats (180-220 g) subjected to spinal cord injury (SCI) were divided into three groups of ten rats each. Group 1 served as control (SCI + Saline), Group 2 received daily dose of ascorbic acid 2,000 mg/kg body weight and group 3 rats received alpha tocopherol daily with the dose of 2,000 mg/kg body weight for 14 days. The Spontaneous coordinate activity (SCA), Basso, Beattie, and Bresnahan (BBB) and Tarlov locomotor scores were used to assess functional recovery of SCI rats. Compared to group 1, group 2 showed statistically insignificant improvement in the SCA, BBB and Tarlov scores at the end of the study. Compared to group 1, group 3 showed statistically significant improvement in the SCA (P < 0.001), BBB (P < 0.001) and Tarlov (P < 0.01) scores at the end of the study. In conclusion, the administration of alpha-tocopherol enhances the reparative effects against SCI and it is more effective than ascorbic acid. PMID- 22068218 TI - Single-fiber electromyography in hyperCKemia: the value of fiber density. AB - Although persistently raised serum creatine kinase (sCK), or hyperCKemia, is considered the biological hallmark of neuromuscular diseases, pauci- or asymptomatic- or isolated-hyperCKemia can often be found. Single-fiber electromyography (SFEMG) is an electrophysiological technique of great value in the assessment of neuromuscular, neuropathic and myopathic disorders. We hypothesize that SFEMG fiber density (FD) evaluation is able to detect subclinical electrophysiological abnormalities indicating a myopathic process in subjects with hyperCKemia. Nineteen subjects with hyperCKemia without evident clinical signs of muscle involvement and 15 healthy controls were studied. Electrophysiological investigations including nerve conduction studies (NCS), quantitative EMG (QEMG), SFEMG with focus on FD measurements, and muscle biopsy were performed. NCS, QEMG, SFEMG were normal in all controls. In subjects with hyperCKemia, NCS were normal; QEMG was abnormal in 5, while both SFEMG and muscle biopsy disclosed abnormalities in 12 subjects. The mean FD value was 2.6 +/- 0.5 in the control and 4 +/- 1.4 (p = 0.003) in the hyperCKemia group. SFEMG revealed subclinical changes in the majority of subjects with hyperCKemia. To the best of our knowledge, this is the first study demonstrating that SFEMG FD evaluation is able to detect the presence of muscle diseases, which are in a subclinical phase and would remain unidentified otherwise. SFEMG may be used to distinguish hyperCKemia associated to asymptomatic muscle disorders from idiopathic hyperCKemia. We believe that SFEMG FD evaluation should be added to the routine examinations in the screening of idiopathic hyperCKemia. PMID- 22068219 TI - Validation of a home environment test battery for supporting assessments in advanced Parkinson's disease. AB - Test sequences in a test battery for Parkinson's disease patients, consisting of self-assessments and motor tests, were carried out repeatedly in a telemedicine setting, during week-long test periods and results were summarized in an 'overall score'. 35 patients in stable and fluctuating conditions (15 age- and gender matched pairs) used the test battery for 1 week, and were then assessed with UPDRS and PDQ-39. This procedure was repeated 1 week later, without treatment changes. Reliability was assessed by intraclass correlation coefficients and Cronbach's alpha. Convergent validity was assessed by Spearman rank correlations and known-groups' validity, by the Mann-Whitney test. According to anonymous usability questionnaires, the patients could easily complete the tasks. Median compliance (93%) and test-retest reliability (0.88) were good. The correlations between overall score and total UPDRS (-0.64) and PDQ-39 (-0.72) were adequate. Median overall score was 18% better in the stable compared to the fluctuating group (p = 0.0014). PMID- 22068221 TI - Interelectron magnetic coupling in electrides with one-dimensional cavity-channel geometry. AB - Dye and coworkers [J. L. Dye, Acc. Chem. Res., 2009, 42, 1564] established experimentally that the strength of interelectron coupling in electrides with open intercavity channels critically depends on the channel diameter but is less sensitive to the channel length. We explain these observations by theoretical analysis of model electrides with a simple geometry. Our model consists of two electrons confined in a dogbone-shaped cavity--two spherical cages connected by a cylindrical channel. The coupling constant J is obtained from the calculated singlet-triplet gap of this system. By approximating the confining potential of the dogbone-shaped cavity with a one-dimensional double-well potential we show that ln(-J/k(B)), where k(B) is the Boltzmann constant, is a near-linear function of ?((1/s) - (1/S)), where s and S are the cross-sectional areas of the channel and the cages, respectively. This prediction is in excellent agreement with the experiment for real electrides that have essentially one-dimensional cavity channel networks. PMID- 22068220 TI - Neurologic signs in relation to cognitive function in subcortical ischemic vascular dementia: a CREDOS (Clinical Research Center for Dementia of South Korea) study. AB - The objective of this study was to investigate the relationship between neurologic signs and cognitive dysfunction in subcortical ischemic vascular dementia (SIVD). 121 patients with SIVD were recruited from multiple nationwide hospitals. The patients' neurologic signs were evaluated using the Focal Neurologic Sign Score (FNSS). The FNSS scores did not correlate with the composite neuropsychology scores and Korean Mini-Mental State Examination scores. The FNSS scores correlated with the letter fluency and Rey-Osterrieth Complex Figure (ROCF) copy scores. Using a multivariate regression analysis controlled for age, sex, and educational level, the FNSS scores had a significant relationship with the letter fluency test scores (R (2) = 0.08, beta = -2.28, p = 0.02) and ROCF copy scores (R (2) = 0.08, beta = -0.42, p = 0.03). These findings suggest that the neurologic signs in patients with SIVD do not correlate with global cognitive functions; however, these signs do correlate with executive dysfunction in these patients. PMID- 22068222 TI - Nilotinib in patients with metastatic melanoma harboring KIT gene aberration. AB - PURPOSE: Patients with metastatic melanoma have a poor prognosis and few treatment options are available. We evaluated the anti-tumor activity and safety of nilotinib, a KIT inhibitor, in patients with metastatic melanoma harboring KIT alterations, either mutations or amplifications. PATIENTS AND METHODS: This study was open-label, single center, prospective phase II clinical trial. Between October 2009 and April 2011, 11 patients with metastatic melanoma harboring KIT gene mutations or KIT gene amplifications were enrolled in the first stage of phase II study and nilotinib was administered orally at a dose of 400 mg twice a day until disease progression or intolerable toxicities. The primary endpoint was response rate and secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). RESULTS: Of 11 patients, 9 patients were evaluable for treatment response. Of 9 patients, three patients had KIT mutations in exon 11, Leu576Pro, Val559Ala and Lys558Arg; and 6 patients had KIT amplifications > 50 copies compared to control DNA. Two patients achieved partial response (22.2%) and 5 patients achieved stable disease (55.6%). In two patients who responded to nilotinib, both had KIT mutations and showed durable response for 8.4 months and 10.0+ months. Of note, one patient with KIT amplification had stable disease with response for 6 months. A decrease in tumor size from baseline was observed in four patients (44.4%). Nilotinib 800 mg/d was very well tolerated with grade 1 nausea and grade 1 dry-eye being the most common adverse events. CONCLUSIONS: We have decided to publish the preliminary results because anti tumor activity of nilotinib was promising in KIT mutated patients. Although our results are preliminary, nilotinib had very favorable toxicity profile with durable response in metastatic melanoma patients with KIT mutations. The anti tumor activity of nilotinib in melanoma patients with KIT amplification is yet to be determined in future studies. Currently, phase II nilotinib trial is ongoing in Korea as multi-center study. PMID- 22068223 TI - Innovative technology in hearing instruments: matching needs in the developing world. AB - Hearing instrument technology research is almost entirely focused on the projected needs of the consumer market in the developed world. However, two thirds of the world's population with hearing impairment live in developing countries and this proportion will increase in future, given present demographic trends. In developing regions, amplification and other hearing health needs may differ from those in industrialized nations, for cultural, health, or economic reasons. World Health Organization estimates indicate that at present only a small percentage of individuals in developing countries who are in need of amplification have access to hearing aid provision. New technologies, such as trainable hearing aids, advanced noise reduction algorithms, feedback reduction circuitry, nano coatings for hearing aid components, and innovative power options, may offer considerable potential benefits, both for individuals with hearing impairment in developing countries and for those who provide hearing health care services in these regions. This article considers the possible supporting role of innovative hearing instrument technologies in the provision of affordable hearing health care services in developing countries and highlights the need for research that considers the requirements of the majority of the world population in need of hearing instrument provision. PMID- 22068224 TI - A method to remove differences in frequency response between commercial hearing aids to allow direct comparison of the sound quality of hearing-aid features. AB - GOAL: We want to remove differences in frequency response between different commercial hearing aids so that we can compare the sound quality of signal processing features from different hearing-aid in a future paired-comparison set up. More specifically, we want to control for the confounding effects of the linear hearing aid response when evaluating nonlinear processing. This article presents a control procedure and evaluates its effectiveness. METHOD: We increased the similarity of hearing-aid recordings in three steps and used both an objective quality metric and listening tests to investigate if the recordings from different hearing aids were perceptually similar. RESULTS: Neither was it sufficient to manually adjust the hearing-aid insertion gain, nor was it sufficient to add an additional bandwidth limitation to the recordings. Only after the application of an inverse filter the perceptual differences between recordings were removed adequately. CONCLUSION: It was possible to level the ground between different hearing devices, so to speak. This will allow future research to evaluate the sound quality of nonlinear signal processing features. PMID- 22068225 TI - Fluvastatin-induced alterations of skeletal muscle function in hypercholesterolaemic rats. AB - Although statins, the most widely used drugs in the treatment of hyperlipidaemia, are generally accepted as efficient and safe drugs their side-effects on skeletal muscle have been reported with increasing frequency. The lack of an animal model in which these side effects would consistently be observed is one of the important drawbacks in studying statin associated myopathy. To overcome this and enable the studying of the effects of fluvastatin on skeletal muscles an animal model with high blood cholesterol levels was developed. In these animals cholesterol levels rose more than seven fold (from 1.5 +/- 0.1 to 10.7 +/- 2.0 mmol/l; n = 15 and 16) with a dramatic increase in low density lipoprotein/high density lipoprotein ratio (from 0.29 +/- 0.02 to 1.56 +/- 0.17). While the latter was reversed by statin treatment, an elevation in blood creatine kinase (CK) level indicated the presence of muscle wasting. Fibers from m. extensor digitorum longus (EDL) showed significant reduction in cross sectional area in the statin treated groups. Statin treatment also decreased the proliferation and fusion of skeletal myotubes in culture. In line with this, resting intracellular calcium concentration ([Ca(2+)](i)) was reduced in statin treated satellite cells and myotubes. On the other hand, in adult skeletal muscle fibers statin treatment increased resting [Ca(2+)](i) (116 +/- 4 nM vs. 151 +/- 5 nM; n = 33 and 34) and decreased both twitch and tetanic force both in EDL and m. soleus. In addition, in m. soleus the duration of twitch and tetanic force was shortened. These results clearly indicate that statin administration in these animals results in a myopathy characterized by decreased muscle force and elevated plasma CK level. PMID- 22068226 TI - Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice. AB - The exact mechanism of selective motor neuron death in amyotrophic lateral sclerosis (ALS) remains still unclear. In the present study, we performed in vivo capillary imaging, directly measured spinal blood flow (SBF) and glucose metabolism, and analyzed whether if a possible flow-metabolism coupling is disturbed in motor neuron degeneration of ALS model mice. In vivo capillary imaging showed progressive decrease of capillary diameter, capillary density, and red blood cell speed during the disease course. Spinal blood flow was progressively decreased in the anterior gray matter (GM) from presymptomatic stage to 0.80-fold of wild-type (WT) mice, 0.61 at early-symptomatic, and 0.49 at end stage of the disease. Local spinal glucose utilization (LSGU) was transiently increased to 1.19-fold in anterior GM at presymptomatic stage, which in turn progressively decreased to 0.84 and 0.60 at early-symptomatic and end stage of the disease. The LSGU/SBF ratio representing flow-metabolism uncoupling (FMU) preceded the sequential pathological changes in the spinal cord of ALS mice and was preferentially found in the affected region of ALS. The present study suggests that this early and progressive FMU could profoundly involve in the whole disease process as a vascular factor of ALS pathology, and could also be a potential target for therapeutic intervention of ALS. PMID- 22068227 TI - How stereological analysis of vascular morphology can quantify the blood volume fraction as a marker for tumor vasculature: comparison with magnetic resonance imaging. AB - To assess angiogenesis noninvasively in a C6 rat brain tumor model, the rapid steady-state-T(1) (RSST(1)) magnetic resonance imaging (MRI) method was used for microvascular blood volume fraction (BVf) quantification with a novel contrast agent gadolinium per (3,6 anhydro) alpha-cyclodextrin (Gd-ACX). In brain tissue contralateral to the tumor, equal BVfs were obtained with Gd-ACX and the clinically approved gadoterate meglumine (Gd-DOTA). Contrary to Gd-DOTA, which leaks out of the tumor vasculature, Gd-ACX was shown to remain vascular in the tumor tissue allowing quantification of the tumor BVf. We sought to confirm the obtained tumor BVf using an independent method: instead of using a 'standard' two dimensional histologic method, we study here how vascular morphometry combined with a stereological technique can be used for three-dimensional assessment of the vascular volume fraction (V(V)). The V(V) is calculated from the vascular diameter and length density. First, the technique is evaluated on simulated data and the healthy rat brain vasculature and is then applied to the same C6 tumor vasculature previously quantified by RSST(1)-MRI with Gd-ACX. The mean perfused V(V) and the BVf obtained by MRI in tumor regions are practically equal and the technique confirms the spatial heterogeneity revealed by MRI. PMID- 22068228 TI - Coactivation of NMDA receptors by glutamate and D-serine induces dilation of isolated middle cerebral arteries. AB - N-methyl-D-aspartate (NMDA) receptors are glutamate-gated cation channels that mediate excitatory neurotransmission in the central nervous system. In addition to glutamate, NMDA receptors are also activated by coagonist binding of the gliotransmitter, D-serine. Neuronal NMDA receptors mediate activity-dependent blood flow regulation in the brain. Our objective was to determine whether NMDA receptors expressed by brain endothelial cells can induce vasodilation of isolated brain arteries. Adult mouse middle cerebral arteries (MCAs) were isolated, pressurized, and preconstricted with norepinephrine. N-methyl-D aspartate receptor agonists, glutamate and NMDA, significantly dilated MCAs in a concentration-dependent manner in the presence of D-serine but not alone. Dilation was significantly inhibited by NMDA receptor antagonists, D-2-amino-5 phosphonopentanoate and 5,7-dichlorokynurenic acid, indicating a response dependent on NMDA receptor glutamate and D-serine binding sites, respectively. Vasodilation was inhibited by denuding the endothelium and by selective inhibition or genetic knockout of endothelial nitric oxide synthase (eNOS). We also found evidence for expression of the pan-NMDA receptor subunit, NR1, in mouse primary brain endothelial cells, and for the NMDA receptor subunit NR2C in cortical arteries in situ. Overall, we conclude that NMDA receptor coactivation by glutamate and D-serine increases lumen diameter in pressurized MCA in an endothelial and eNOS-dependent mechanism. PMID- 22068229 TI - Fast-mapping placeholders: Using words to talk about kinds. AB - Fast-mapping is the ability to acquire a word rapidly on the basis of minimal information. As proposed by Carey (1978), we assume that children are able to achieve fast-mapping because their initial word meanings are skeletal placeholders that will be extended gradually over time. In this paper we propose that a notion of "kind" is fundamental to children's initial mappings for object labels. We illustrate this point by considering the acquisition of generic noun phrases, which are understood by children as kind-referring from very early on. We argue that the acquisition of generics has implications for mechanisms of word learning. Evidence suggests that generics cannot be acquired solely on the basis of associative learning mechanisms; rather, they are a default interpretation for young children. PMID- 22068230 TI - Recent advances in understanding ulcerative colitis. AB - Ulcerative colitis, one of the two main forms of inflammatory bowel disease, is characterized by inflammation of the large bowel with constant involvement of the rectum, and a possible continuous retrograde distribution up to the cecum. Typical macroscopic lesions are mucosal ulcerations, with immune cell infiltration and cryptic abscesses at histology. Ulcerative colitis usually manifests with bloody diarrhea, is associated with a number of extra-intestinal manifestations, and may be acutely complicated by toxic megacolon. Longstanding disease may predispose to the development of colorectal cancer. Therapeutic options include mesalazine, corticosteroids, immunomodulators and biologic agents; however, if these treatments fail, the only available therapeutic choice remaining is the surgical removal of the colon. This review emphasizes novel concepts in the basic aspects of ulcerative colitis, and, in addition to the current clinical and diagnostic knowledge, it also describes new treatment options for this condition. PMID- 22068231 TI - Discovery of ATL: an odyssey in restrospect. AB - Forty years have passed since our initial description of peculiar cases of adult onset leukemia with abnormal cells having multi-convoluted nuclei and T cell properties, frequent in the southern regions of Japan in the early 1970s. Retrospectively, the study of adult T cell leukemia (ATL) and the related virus HTLV-I was a forerunner for all of human retrovirology, in which AIDS and the related retrovirus HIV were identified a few years later in the 1980s. Using the anti-TAC monoclonal antibody generated by the late Takashi Uchiyama during his stay in T. A. Waldmann's laboratory in NIH Bethesda, a cDNA encoding IL-2Ralpha chain was cloned by our group in Kyoto and by Waldmann's group in Bethesda. Abnormal IL-2Ralpha chain expression and the IL-2 dependency of ATL cell lines greatly contributed to the study of leukemogenesis of ATL. A new soluble factor named ADF/ATL-derived factor was also detected in ATL cell lines. After years of study, ADF proved to be a first human counterpart of thiol-related oxido reductase thioredoxin/TRX, which opened the field of redox regulation of cell signaling involved in a variety of diseases. Close interaction among Drs. Kimishige Ishizaka, Kiyoshi Takastuki and T. A. Waldmanns before ATL and HTLV-I study was an essential base for our initiation of ATL research with Takashi Uchiyama and many other colleagues. PMID- 22068232 TI - Cofilin-mediated F-actin severing is regulated by the Rap GTPase and controls the cytoskeletal dynamics that drive lymphocyte spreading and BCR microcluster formation. AB - When lymphocytes encounter APCs bearing cognate Ag, they spread across the surface of the APC to scan for additional Ags. This is followed by membrane contraction and the formation of Ag receptor microclusters that initiate the signaling reactions that lead to lymphocyte activation. Breakdown of the submembrane cytoskeleton is likely to be required for the cytoskeleton reorganization that drives cell spreading and for removing physical barriers that limit Ag receptor mobility. In this report, we show that Ag receptor signaling via the Rap GTPases promotes the dephosphorylation and activation of the actin severing protein cofilin and that this results in increased severing of cellular actin filaments. Moreover, we show that this cofilin-mediated actin severing is critical for the changes in actin dynamics that drive B and T cell spreading, for the formation of BCR microclusters, and for the increased mobility of BCR microclusters within the plasma membrane after BCR engagement. Finally, using a model APC, we show that activation of this Rap-cofilin signaling module controls the amount of Ag that is gathered into BCR microclusters and that this is directly related to the magnitude of the resulting BCR signaling that is initiated during B cell-APC interactions. Thus, Rap-dependent activation of cofilin is critical for the early cytoskeletal changes and BCR reorganization that are involved in APC-dependent lymphocyte activation. PMID- 22068233 TI - CpG protects human monocytic cells against HIV-Vpr-induced apoptosis by cellular inhibitor of apoptosis-2 through the calcium-activated JNK pathway in a TLR9 independent manner. AB - Monocytic cells survive HIV replication and consequent cytopathic effects because of their decreased sensitivity to HIV-induced apoptosis. However, the mechanism underlying this resistance to apoptosis remains poorly understood. Lymphocytic cells are exposed to microbial products because of their translocation from the gut in persons with chronic HIV infections or following coinfections. We hypothesized that activation of monocytic cells by such microbial products through interaction with corresponding TLRs may confer antiapoptotic signals. Using HIV-viral protein R (Vpr)(52-96) peptide as a model apoptosis-inducing agent, we demonstrated that unlike monocyte-derived macrophages, undifferentiated primary human monocytes and promonocytic THP-1 cells are highly susceptible to Vpr(52-96)-induced apoptosis. Interestingly, monocytes and THP-1 cells stimulated with TLR9 agonist CpG induced almost complete resistance to Vpr(52-96)-induced apoptosis, albeit through a TLR9-independent signaling pathway. Moreover, CpG selectively induced the antiapoptotic cellular inhibitor of apoptosis (c-IAP)-2 protein and inhibition of the c-IAP-2 gene by either specific small interfering RNA or synthetic second mitochondrial activator of caspases mimetic reversed CpG induced resistance against Vpr(52-96)-mediated apoptosis. We demonstrated that c IAP-2 is regulated by the JNK and calcium signaling pathway, in particular calmodulin-dependent protein kinase-II. Furthermore, inhibition of JNK and the calcium signaling including the calmodulin-dependent protein kinase-II by either pharmacological inhibitors or their specific small interfering RNAs reversed CpG induced protection against Vpr(52-96)-mediated apoptosis. We also show that CpG induced JNK phosphorylation through activation of the calcium signaling pathway. Taken together, our results suggest that CpG-induced protection may be mediated by c-IAP-2 through the calcium-activated JNK pathway via what appeared to be TLR9 independent signaling pathways. PMID- 22068234 TI - CD84 negatively regulates IgE high-affinity receptor signaling in human mast cells. AB - CD84 is a self-binding receptor from the CD150 (or signaling lymphocyte activation molecule [SLAM]) family that is broadly expressed in hematopoietic cells. It has been described that the adaptors SLAM-associated protein (SAP) and EWS-FLI1-activated transcript 2 (EAT-2) are critical for CD150 family members' signaling and function. We observed that human mast cells express CD84 but lack SAP or EAT-2, that CD84 is tyrosine phosphorylated upon FcepsilonRI engagement, and that the release of granule contents is reduced when FcepsilonRI is coengaged with CD84 in LAD2 and human CD34(+)-derived mast cells. In addition, we observed that the release of IL-8 and GM-CSF was also reduced in FcepsilonRI/CD84 costimulated cells as compared with FcepsilonRI/Ig control. To understand how CD84 downregulates FcepsilonRI-mediated function, we analyzed signaling pathways affected by CD84 in human mast cells. Our results showed that CD84 dampens FcepsilonRI-mediated calcium mobilization after its co-cross-linking with the receptor. Furthermore, FcepsilonRI-mediated Syk-linker for activation of T cells phospholipase C-gamma1 axis activity is downregulated after CD84 stimulation, compared with FcepsilonRI/Ig control. The inhibitory kinase Fes phosphorylates mainly the inhibitory motif for CD84. Moreover, Fes, which has been described to become phosphorylated after substrate binding, also gets phosphorylated when coexpressed with CD84. Consistently, Fes was observed to be more phosphorylated after CD84 and FcepsilonRI co-cross-linking. The phosphorylation of the protein phosphatase Src homology region 2 domain-containing phosphatase-1 also increases after CD84 and FcepsilonRI coengagement. Taken together, our results show that CD84 is highly expressed in mast cells and that it contributes to the regulation of FcepsilonRI signaling in SAP- and EAT-2-independent and Fes- and Src homology region 2 domain-containing phosphatase-1-dependent mechanisms. PMID- 22068235 TI - Pancreatic islets engineered with SA-FasL protein establish robust localized tolerance by inducing regulatory T cells in mice. AB - Allogeneic islet transplantation is an important therapeutic approach for the treatment of type 1 diabetes. Clinical application of this approach, however, is severely curtailed by allograft rejection primarily initiated by pathogenic effector T cells regardless of chronic use of immunosuppression. Given the role of Fas-mediated signaling in regulating effector T cell responses, we tested if pancreatic islets can be engineered ex vivo to display on their surface an apoptotic form of Fas ligand protein chimeric with streptavidin (SA-FasL) and whether such engineered islets induce tolerance in allogeneic hosts. Islets were modified with biotin following efficient engineering with SA-FasL protein that persisted on the surface of islets for >1 wk in vitro. SA-FasL-engineered islet grafts established euglycemia in chemically diabetic syngeneic mice indefinitely, demonstrating functionality and lack of acute toxicity. Most importantly, the transplantation of SA-FasL-engineered BALB/c islet grafts in conjunction with a short course of rapamycin treatment resulted in robust localized tolerance in 100% of C57BL/6 recipients. Tolerance was initiated and maintained by CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, as their depletion early during tolerance induction or late after established tolerance resulted in prompt graft rejection. Furthermore, Treg cells sorted from graft-draining lymph nodes, but not spleen, of long-term graft recipients prevented the rejection of unmodified allogeneic islets in an adoptive transfer model, further confirming the Treg role in established tolerance. Engineering islets ex vivo in a rapid and efficient manner to display on their surface immunomodulatory proteins represents a novel, safe, and clinically applicable approach with important implications for the treatment of type 1 diabetes. PMID- 22068236 TI - Microbiota downregulates dendritic cell expression of miR-10a, which targets IL 12/IL-23p40. AB - Commensal flora plays important roles in the regulation of the gene expression involved in many intestinal functions and the maintenance of immune homeostasis, as well as in the pathogenesis of inflammatory bowel diseases. The microRNAs (miRNAs), a class of small, noncoding RNAs, act as key regulators in many biological processes. The miRNAs are highly conserved among species and appear to play important roles in both innate and adaptive immunity, as they can control the differentiation of various immune cells, as well as their functions. However, it is still largely unknown how microbiota regulates miRNA expression, thereby contributing to intestinal homeostasis and pathogenesis of inflammatory bowel disease. In our current study, we found that microbiota negatively regulated intestinal miR-10a expression, because the intestines, as well as intestinal epithelial cells and dendritic cells of specific pathogen-free mice, expressed much lower levels of miR-10a compared with those in germ-free mice. Commensal bacteria downregulated dendritic cell miR-10a expression via TLR-TLR ligand interactions through a MyD88-dependent pathway. We identified IL-12/IL-23p40, a key molecule for innate immune responses to commensal bacteria, as a target of miR-10a. The ectopic expression of the miR-10a precursor inhibited, whereas the miR-10a inhibitor promoted, the expression of IL-12/IL-23p40 in dendritic cells. Mice with colitis expressing higher levels of IL-12/IL-23p40 exhibited lower levels of intestinal miR-10a compared with control mice. Collectively, our data demonstrated that microbiota negatively regulates host miR-10a expression, which may contribute to the maintenance of intestinal homeostasis by targeting IL-12/IL 23p40 expression. PMID- 22068237 TI - Cutting edge: A role for inside-out signaling in TCR regulation of CD28 ligand binding. AB - Efficient T cell activation depends on the engagement of both TCR and CD28, although the molecular mechanisms that control this signal integration are not fully understood. Using fluorescence resonance energy transfer, we show that T cell activation can drive a reorientation of the cytosolic tails of the CD28 dimer. However, this is not mediated through CD28 ligand binding. Rather, TCR signaling itself mediates this conformation change in CD28. We also show that TCR signaling can induce CD28-ligand interactions. Although the CD28 dimer appears to bind ligand monovalently in solution, we show that both ligand binding sites are required to efficiently recruit CD28 to the immunological synapse. These results suggest, that analogous to the cross-talk from TCR that regulates integrin activation, TCR-initiated inside-out signaling may induce a conformational change to the extracellular domains of CD28, enabling ligand binding and initiating CD28 signaling. PMID- 22068238 TI - Silicon nanowire ion sensitive field effect transistor with integrated Ag/AgCl electrode: pH sensing and noise characteristics. AB - We have fabricated Si nanowire (SiNW) based ion-sensitive field effect transistors (ISFETs) for biosensing applications. The ability to prepare a large number of sensors on a wafer, the use of standard silicon microfabrication techniques resulting in cost savings, and potential high sensitivity are significant advantages in favor of nanoscale SiNW ISFETs. The SiNW ISFETs with embedded Ag/AgCl reference electrode were fabricated on a standard silicon-on insulator wafer using electron-beam lithography and conventional semiconductor processing technology. The current-voltage characteristics show an n-type FET behavior with a relatively high on/off current ratio, reasonable sub-threshold swing value, and low gate-leakage current. The pH responses of the ISFETs with different pH solutions were characterized at room temperature which showed a clear lateral shift of the drain current vs. gate voltage curve with a change in the pH value of the solution and a sensitivity of 40 mV pH(-1). The low frequency noise characteristics were investigated to evaluate the signal to noise ratio and sensing limit of the devices. PMID- 22068239 TI - Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines. AB - Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH(4)OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction. PMID- 22068241 TI - Comment: Use of recalibrated serum creatinine concentrations for adjustment of drug dosages: determination of values compatible with conventional dosing recommendations. PMID- 22068242 TI - The value of pharmacy services on a short-term medical mission trip: description of services and assessment of team satisfaction. AB - BACKGROUND: Pharmacists should be key members of a medical mission trip by providing assistance with medication knowledge and therapeutics. OBJECTIVE: To determine the value of a pharmacist as a member of a medical mission team through (1) pharmacy interventions on 2 medical teams and 1 women's health team and (2) team satisfaction with the pharmacy services. METHODS: Pharmacy interventions were documented by 2 medical teams and 1 women's health team and included, but were not limited to, dosing recommendations, medication selection, and therapeutic substitution. Team satisfaction was determined from a 10-question survey administered on the last clinical day to all team members except pharmacists, pharmacy students, and physical therapists. RESULTS: The pharmacy service dispensed 2119 prescriptions, with an average number of prescriptions of 1.84 per patient. A total of 2340 interventions were provided by the pharmacy service, averaging 2.04 interventions per patient and 1.1 interventions per prescription. The survey indicated that a pharmacist serves an integral role for the multidisciplinary medical team. CONCLUSIONS: Pharmacists play an important role in a short-term medical mission trip by serving as sources for medication knowledge and ensuring appropriate medication therapy management as part of the interdisciplinary team. PMID- 22068243 TI - Use of dexmedetomidine to discontinue high-dose fentanyl. PMID- 22068245 TI - A new, vitamin D-based, multidimensional nomogram for the diagnosis of primary hyperparathyroidism. AB - OBJECTIVE: To refine the diagnostic criteria for primary hyperparathyroidism (1 degrees HPT) to identify atypical patients, in whom serum calcium, parathyroid hormone (PTH), or both are within the "normal" range. METHODS: Total serum calcium, intact PTH, and 25-hydroxyvitamin D [25(OH)D] levels were measured in patients with 1 degrees HPT and healthy patient groups. Multivariate analysis of healthy patient data first identified factors that significantly affected PTH levels and defined a new PTH reference range with a mathematical model. That nomogram was then validated for prediction of atypical 1 degrees HPT in patients with surgically confirmed disease. RESULTS: On multivariate analysis, calcium (P = .0002), 25(OH)D (P<.0001), and age (P = .015) independently affected PTH. With these variables, we created a 4-dimensional nomogram that distinguished normal patients from those with hyperparathyroid states. Mathematically, this nomogram predicts 1 degrees HPT when the measured serum PTH value is higher than PTH calculated by the following formula: PTH (pg/mL) = 120 - [6 * calcium (mg/dL)] - [0.52 * 25(OH)D (ng/mL)] + [0.26 * patient age (years)]. When applied to our surgical group of patients, this nomogram successfully identified 100% of patients (238 of 238) with classic 1 degrees HPT, 84% (64 of 76) with normocalcemic 1 degrees HPT, and 54% (20 of 37) with 1 degrees HPT and normal PTH. CONCLUSION: This study uniquely defines a patient-specific upper limit of normal for PTH based on the readily available variables of serum calcium, 25(OH)D, and patient age. Our nomogram may allow for more rapid definitive diagnosis and treatment of 1 degrees HPT in patients with atypical presentations. PMID- 22068244 TI - A review of supernumerary and absent limbs and digits of the upper limb. AB - For years people have been enamored by anomalies of the human limbs, particularly supernumerary and absent limbs and digits. Historically, there are a number of examples of such anomalies, including royal families of ancient Chaldea, tribes from Arabia, and examples from across nineteenth century Europe. The development of the upper limbs in a growing embryo is still being elucidated with the recent advent of homeobox genes, but researchers agree that upper limbs develop between stages 12-23 through a complex embryological process. Maternal thalidomide intake during limb development is known to cause limb reduction and subsequent amelia or phocomelia. Additionally, a number of clinical reports have illustrated different limb anomaly cases, with each situation unique in phenotype and developmental abnormality. Supernumerary and absent limbs and digits are not unique to humans, and a number of animal cases have also been reported. This review of the literature illustrates the historical, anatomical, and clinical aspects of supernumerary and absent limbs and digits for the upper limb. PMID- 22068246 TI - Finding the right balance between resistance and sensitivity: a review of the cardiac manifestations of the syndrome of resistance to thyroid hormone and the implications for treatment. AB - OBJECTIVE: To review cardiac manifestations in the syndrome of resistance to thyroid hormone (RTH) and to question the general recommendation that the thyroid stimulating hormone (TSH) value be the guide to thyroid hormone replacement. METHODS: The syndrome of RTH is caused by mutations in the carboxy-terminal portion of the beta isoform of the thyroid hormone receptor, resulting in variable clinical manifestations. It is generally recommended that the replacement of thyroid hormone in patients with RTH be guided by the serum TSH concentration. The variable responsiveness of tissues to thyroid hormone, however, makes it difficult to balance the correct replacement dose. We present a case that brings into question the conventional wisdom about the replacement dose of thyroid hormone in this scenario, and we review the pertinent literature. RESULTS: A 54-year-old man with RTH was treated with levothyroxine and increasing doses of liothyronine sodium as part of an evaluation of RTH. On day 10 of the protocol, he developed atrial fibrillation despite a normal level of TSH (1.1 mIU/L). Administration of liothyronine was discontinued, and cardioversion was planned; however, the patient's heart rhythm converted spontaneously to normal sinus rhythm. CONCLUSION: Replacement of thyroid hormone in patients with RTH should include careful monitoring of thyrotoxic cardiac side effects in addition to consideration of normalization of the TSH level. PMID- 22068247 TI - Hurthle cell carcinoma of the thyroid presenting as thyrotoxicosis. AB - OBJECTIVE: To report a case of hyperthyroidism associated with Hurthle cell carcinoma and to review the literature regarding this relationship. METHODS: We describe the clinical, biochemical, radiologic, and pathologic data of a patient with Hurthle cell carcinoma associated with thyrotoxicosis and reversible heart failure. We discuss the mechanistic aspects and review previously reported cases of functional Hurthle cell carcinomas. RESULTS: A 43-year-old woman presented with thyrotoxicosis and nonischemic cardiomyopathy. She had a "hot" nodule in the left lobe of the thyroid on sodium pertechnetate scan. She underwent a left hemithyroidectomy and isthmusectomy. Pathologic findings revealed a minimally invasive Hurthle cell carcinoma. On follow-up, the dilated cardiomyopathy had resolved. The association of thyroid carcinoma with thyrotoxicosis is rare. CONCLUSIONS: Some Hurthle cell carcinomas can be functional and lead to thyrotoxicosis. To our knowledge, we present the first case of reversible dilated cardiomyopathy due to thyrotoxicosis originating from Hurthle cell carcinoma. PMID- 22068248 TI - Similar clinical features among patients with severe adult growth hormone deficiency diagnosed with insulin tolerance test or arginine or glucagon stimulation tests. AB - OBJECTIVE: To determine whether insulin tolerance tests (ITTs), arginine stimulation tests (ASTs), and glucagon stimulation tests (GST) identify patients who have similar clinical features of growth hormone (GH) deficiency when a diagnostic GH threshold of 3 MUg/L is used. METHODS: Data were obtained from the KIMS database (Pfizer International Metabolic Database). Comparisons were made between patients who underwent ITT, AST, or GST for GH peak, body mass index, lipids, waist circumference, waist-to-hip ratio, and quality of life. RESULTS: A total of 5453 tests were available from 4867 patients registered in the database (ITT = 3111, AST = 1390, GST = 952). Significant (P<.001) intraindividual correlations were observed between the GH peaks for ITT vs AST (r = 0.655), ITT vs GST (r = 0.445), and AST vs GST (r = 0.632). GH peaks in response to all tests were negatively correlated to the number of additional pituitary hormone deficiencies and positively correlated to the insulinlike growth factor 1 standard deviation score. Body mass index had a negative influence on all 3 tests. Most clinical variables did not differ between the groups when comparing GH-deficient patients according to the diagnostic test used. The only exceptions that showed any difference were body mass index (slightly higher in the AST and GST groups), triglyceride levels (increased in the GST group), and insulinlike growth factor 1 (standard deviation score) (lower in the ITT and AST groups than in the GST group). Waist circumference was greater and quality of life was worse in the GST group than in the other groups. CONCLUSIONS: The ITT, AST, and GST produce similar GH peaks, are influenced by similar clinical factors, and identify patients with similar features of GH deficiency at a diagnostic threshold of 3 MUg/L. PMID- 22068249 TI - Transition care of patients with growth hormone deficiency from pediatric endocrinologists to adult endocrinologists. AB - OBJECTIVE: To review whether growth hormone (GH) therapy should be continued into young adulthood, beyond achievement of final height, when GH deficiency persists, to summarize the recent evidence of the benefits of GH treatment during the transition period, and to address currently debated issues involving diagnosis, treatment, and transition of care. METHODS: Primary literature was reviewed in the following areas: the benefits and risks of GH therapy during the transition period, the diagnostic criteria for GH deficiency and recommended testing procedures during transition, the optimal dose of GH therapy during transition, and the factors to consider in the transition of care from the pediatric to the adult endocrinologist. RESULTS: Studies support the continuation of GH therapy through the transition period until accrual of peak bone mass, rather than cessation of GH treatment when adult height has been achieved. Continued GH treatment in patients with persistent GH deficiency after achieving final height has been associated with significant additional bone maturation and improved overall metabolic profile. The selection of the most appropriate methods and cutoff values for retesting GH deficiency during the transition period remains a challenge. Reassessment of the optimal GH dose is a key component of transition care. CONCLUSION: For patients with GH deficiency that will likely persist into adulthood, it is important to begin discussing possible continuation of GH treatment early in the management of GH deficiency. Clear communication between pediatric and adult endocrinologists will be needed to determine the timing of the patient-care transition and to minimize the interruption of GH therapy during the transition period. PMID- 22068250 TI - Successful treatment of prediabetes in clinical practice: targeting insulin resistance and beta-cell dysfunction. AB - OBJECTIVE: To determine the effectiveness of targeted pharmacologic interventions to reverse documented pathophysiologic abnormalities in prediabetes. METHODS: Patients with impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) were treated with insulin sensitizers (pioglitazone + metformin) or insulin sensitizers + exenatide on the basis of oral glucose tolerance testing-derived indices of insulin resistance and impaired beta-cell function. Patients who declined pharmacologic therapy received lifestyle modification only. RESULTS: One hundred five patients with IGT and/or IFG were treated with insulin sensitizers (pioglitazone + metformin) (n = 40), insulin sensitizers + exenatide (n = 47), or lifestyle modification only (n = 18). After a mean follow-up period of 8.9 months, the lifestyle modification group demonstrated no significant changes in fasting plasma glucose, plasma glucose area under the curve during oral glucose tolerance testing, insulin sensitivity, or beta-cell function. In the pioglitazone + metformin group (24 hours off medication), fasting plasma glucose fell from 109 to 102 mg/dL; plasma glucose area under the curve decreased by 12.0%; insulin sensitivity and beta-cell function improved by 42% and 50%, respectively (all P<.001); 14.3% converted to normal glucose tolerance; and no patient developed diabetes. In the pioglitazone + metformin + exenatide group (24 hours off medication), fasting plasma glucose fell from 109 to 98 mg/dL; plasma glucose area under the curve decreased by 21.2%; insulin sensitivity and beta cell function improved by 52% and 109%, respectively (all P<.001); 59.1% of patients with IGT reverted to normal glucose tolerance; and no patient developed diabetes. CONCLUSIONS: Targeted pathophysiologic therapy based on oral glucose tolerance test-derived measures of insulin sensitivity and beta-cell function can be implemented in general internal medicine and endocrine practice and is associated with marked improvement in glucose tolerance and reversion of prediabetes to normal glucose tolerance in more than 50% of patients. PMID- 22068251 TI - Three large, functioning cystic parathyroid adenomas. AB - OBJECTIVE: To report a very rare case of 3 large, functioning cystic parathyroid adenomas causing primary hyperparathyroidism. METHODS: We present the history, clinical findings, laboratory test results, radiologic findings, endocrine workup results, intraoperative surgical challenges, and surgical pathology report of the study patient. We review the literature and discuss the importance of intraoperative parathyroid hormone (PTH) measurement in such cases. RESULTS: A 79 year-old woman presented with primary hyperparathyroidism and elevated levels of calcium and PTH. Localization studies confirmed the presence of a large right upper parathyroid adenoma. On exploration, a very large cystic parathyroid gland was identified at that location. Because intraoperative PTH levels remained elevated, further exploration was pursued, which revealed 2 more large cystic glands on the left side that were resected. This resulted in an adequate but slow PTH drop. The right lower gland appeared normal. On follow-up 4 days and 6 weeks after surgery, the calcium and PTH levels had normalized. CONCLUSION: This case highlights the aspects of intraoperative PTH use and underscores the need to exclude multigland disease even in the setting of a very large parathyroid cyst with concordant localization studies. PMID- 22068253 TI - An outpatient-based clinical program for diabetes prevention: an update. AB - OBJECTIVE: To update outcomes of the Diet-Exercise-Activity-Lifestyle (DEAL) program, a clinic-based diabetes prevention intervention. METHODS: Changes in weight, fasting blood glucose, and 2-hour glucose after a 75-g oral glucose tolerance test were evaluated in patients who enrolled in the DEAL program between January 2007 and August 2009. RESULTS: The 221 qualified participants had a mean age of 62 years, weight of 87.4 kg, body mass index of 31.2 kg/m2, fasting glucose level of 109 mg/dL, and 2-hour glucose value of 138 mg/dL. Among the program participants, 67% were women and 88% were white; 56% had isolated impaired fasting glucose, 5% had impaired glucose tolerance only, and 39% had both. The 6-month follow-up medical appointment was kept by 72% of program participants, but only 56% attended the 12-month visit. By 6 months after baseline, 59% had significantly lower fasting glucose concentrations, 59% had improvement in 2-hour glucose levels, and 61% had weight loss. Nearly 40%, however, were nonresponders and had increased fasting glucose, 2-hour glucose, and weight by 6 months. By the 12-month visit, significant declines in fasting glucose (P<.001), 2-hour glucose (P<.001), and weight (P = .008) occurred in comparison with baseline values; however, no significant changes occurred in these measures between the 6- and 12-month visits (P>.30 for all). CONCLUSION: Most DEAL participants showed improvement in glucose levels and weight, but some patients exhibited worsening glucose intolerance. Factors underlying nonresponse need to be identified. Ongoing experience and analysis should help revise the DEAL program so that outcomes for all participating patients will improve. PMID- 22068254 TI - Clinical effects of long-term metreleptin treatment in patients with lipodystrophy. AB - OBJECTIVE: To evaluate the long-term clinical effect of treatment with metreleptin (an analogue of human leptin) on glycemic and lipid abnormalities and markers of hepatic steatosis in patients with inherited or acquired lipodystrophy. METHODS: Fifty-five patients (36 with generalized lipodystrophy and 19 with partial lipodystrophy) with at least 1 of 3 metabolic abnormalities (diabetes mellitus, fasting triglyceride level >=200 mg/dL, and insulin resistance) and low leptin levels received subcutaneous injections of metreleptin once or twice daily in an ongoing clinical trial at the National Institutes of Health. RESULTS: At baseline, hemoglobin A1c-8.5% +/- 2.1% (mean +/- standard deviation [SD])-and triglycerides-479 +/- 80 mg/dL (geometric mean +/- standard error [SE])-were substantially elevated. Robust and sustained reductions in both variables were evident for the observed patient population during a 3-year metreleptin treatment period (-2.1% +/- 0.5% [mean +/- SE] and -35.4% +/- 13.7% [mean +/- SE], respectively). Mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at baseline (100 +/- 120 U/L and 71 +/- 77 U/L [mean +/- SD], respectively) and decreased by -45 +/- 19 U/L and -33 +/- 14 U/L (mean +/- SE), respectively, during the 3-year metreleptin treatment period. Improvements in hemoglobin A1c, triglycerides, ALT, and AST were more pronounced in the subsets of patients having elevated levels at baseline. The most notable adverse events observed in this patient population were likely attributable to underlying metabolic abnormalities or comorbidities. CONCLUSION: Metreleptin treatment substantially reduced glycemic variables, triglycerides, and liver enzymes (ALT and AST) and demonstrated durability of response throughout a 3-year treatment period. These results support metreleptin as a potential treatment for certain metabolic disorders (for example, diabetes mellitus and hypertriglyceridemia) associated with lipodystrophy. PMID- 22068255 TI - Retroperitoneal masses mimicking adrenal tumors. AB - OBJECTIVE: To report 10 cases of neoplasms that were initially thought to be primarily adrenal-derived masses but were later confirmed as tumors of a different origin. METHODS: Between 2000 and 2011, a total of 229 patients underwent adrenalectomy at our institution. Of this overall group, 10 patients had retroperitoneal pathologic conditions mimicking adrenal tumors. Using an institutional review board-approved database, we reviewed the clinical, biochemical, and radiologic characteristics of these 10 patients. RESULTS: The study cohort consisted of 4 male and 6 female patients. The mean age of these 10 patients was 48 years. The pathologic conditions included schwannoma (n = 3), leiomyosarcoma (n = 2), and 1 each of metastatic angiosarcoma, metastatic granulosa cell tumor, retroperitoneal hematoma, perivascular epithelioid cell tumor, and bronchogenic cyst. The patient with angiosarcoma had elevated plasma and urine catecholamines and a positive metaiodobenzylguanidine scan, whereas the others had normal findings on biochemical work-up. A percutaneous biopsy was performed preoperatively in 2 patients. All patients, except the patient with hematoma, underwent abdominal exploration, which was laparoscopic in 5, open in 2, and robotic in 2. With exclusion of the patients with angiosarcoma and hematoma, resection was possible in all the remaining patients. CONCLUSION: In this report we describe our experience with retroperitoneal masses mimicking adrenal tumors. Increased awareness of these unusual pathologic conditions is important for appropriate clinical management of these tumors. The presentation of the patients and the surgical management of these individual pathologic entities are highlighted. PMID- 22068256 TI - Delayed treatment of papillary thyroid carcinoma arising from struma ovarii in a patient with history of bilateral salpingo-oophorectomy: a case report. AB - OBJECTIVE: We present a case of papillary thyroid carcinoma arising from struma ovarii treated erroneously as ovarian adenocarcinoma for more than 3 years. METHODS: We report clinical, surgical, laboratory, and imaging findings of the study patient and review the relevant literature. RESULTS: A 64-year-old woman was treated for ovarian adenocarcinoma for more than 3 years before it was determined that she likely had papillary thyroid carcinoma arising from struma ovarii. This is the first reported case of thyroid carcinoma arising from struma ovarii in a patient with a history of bilateral salpingo-oophorectomy. Possible etiologies include residual ovarian tissue after oophorectomy, ectopic thyroid, or metastatic thyroid cancer. CONCLUSIONS: It is important to include struma ovarii and thyroid carcinoma arising from struma ovarii in the differential diagnosis, even with a history of bilateral salpingo-oophorectomy. This case emphasizes the importance of effective communication among the pathologist, oncologist, and surgeon to ensure timely initiation of appropriate therapy and reduced patient morbidity. PMID- 22068257 TI - Visual vignette. Hypothyroidism-associated myopathy. PMID- 22068259 TI - Visual vignette. Primary adrenal insufficiency attributable to bilateral hemorrhagic adrenal metastatic lesions from poorly differentiated non-small cell lung carcinoma. PMID- 22068258 TI - Case report of acute necrotizing pancreatitis associated with combination treatment of sitagliptin and exenatide. AB - OBJECTIVE: To report the first postmarketing case of necrotizing pancreatitis in a patient on combination therapy of sitagliptin and exenatide. METHODS: We describe the patient's clinical presentation, laboratory test results, imaging, and autopsy findings. RESULTS: A 76-year-old woman with a history of type 2 diabetes mellitus presented with severe abdominal pain, vomiting, and fever requiring hospital admission. She had been treated with exenatide for 3 years to manage her diabetes mellitus. A few weeks before presentation, sitagliptin was added, presumably to further optimize her glycemic control. Acute pancreatitis was diagnosed during hospital admission. At initial presentation, her serum amylase concentration was 1136 U/L (reference range, 10-130 U/L) and her lipase concentration was greater than 3500 U/L (reference range, 0-75 U/L). In addition, computed tomography of the abdomen and pelvis demonstrated extensive previous cholecystectomy, reported no alcohol consumption, and had a normal lipid profile. Although she had a long-standing history of diabetes mellitus, she had no history of pancreatitis or other risk factors that would have caused her to develop the underlying condition. After initial brief improvement, her symptoms worsened, and despite aggressive care, her clinical state deteriorated and she died. Autopsy findings demonstrated acute necrotizing pancreatitis with complete digestion of the pancreas. CONCLUSIONS: Considering the temporal relationship of her symptoms to the addition of sitagliptin to her existing exenatide regimen, this case strongly suggests a possible causal link between exenatide or sitagliptin (or the combination of the 2 drugs) and the etiology of pancreatitis in this patient. PMID- 22068260 TI - Trichotemnomania: hair loss mediated by a compulsive habit not admitted by patients. PMID- 22068261 TI - (AEDPH3).(BtaH): a novel supramolecular plaster with formaldehyde adsorption and formaldehyde/ultraviolet ray-induced luminescence switching performance. AB - A novel supramolecular plaster, (AEDPH(3)).(BtaH) (1), is synthesised and characterized. The supramolecular plaster is easy to synthesise and process, and displays good mechanical properties. It can adsorb and eliminate formaldehyde (HCHO) with high efficiency and exhibits very interesting HCHO/ultraviolet ray induced luminescence switching. PMID- 22068262 TI - Simultaneous hydrogen utilization and in situ biogas upgrading in an anaerobic reactor. AB - The possibility of converting hydrogen to methane and simultaneous upgrading of biogas was investigated in both batch tests and fully mixed biogas reactor, simultaneously fed with manure and hydrogen. Batch experiments showed that hydrogen could be converted to methane by hydrogenotrophic methanogenesis with conversion of more than 90% of the consumed hydrogen to methane. The hydrogen consumption rates were affected by both P(H2) (hydrogen partial pressure) and mixing intensity. Inhibition of propionate and butyrate degradation by hydrogen (1 atm) was only observed under high mixing intensity (shaking speed 300 rpm). Continuous addition of hydrogen (flow rate of 28.6 mL/(L/h)) to an anaerobic reactor fed with manure, showed that more than 80% of the hydrogen was utilized. The propionate and butyrate level in the reactor was not significantly affected by the hydrogen addition. The methane production rate of the reactor with H2 addition was 22% higher, compared to the control reactor only fed with manure. The CO2 content in the produced biogas was only 15%, while it was 38% in the control reactor. However, the addition of hydrogen resulted in increase of pH (from 8.0 to 8.3) due to the consumption of bicarbonate, which subsequently caused slight inhibition of methanogenesis. PMID- 22068263 TI - On the role of beta-cyanoalanine synthase (CAS) in metabolism of free cyanide and ferri-cyanide by rice seedlings. AB - A study was conducted to investigate the contribution of beta-cyanoalanine synthase (CAS) to the botanical metabolism of free cyanide and iron cyanides. Seedlings of rice (Oryza sativa L. cv. XZX 45) were grown hydroponically and then amended with free cyanide (KCN) or ferri-cyanide [K(3)Fe(CN)(6)] into the growth media. Total cyanide, free cyanide, and Fe(3+)/Fe(2+) in aqueous solution were analyzed to identify the speciation of K(3)Fe(CN)(6). Activity of CAS in different parts of the rice seedlings was also assayed in vivo and results indicated that dissociation of K(3)Fe(CN)(6) to free cyanide in solution was negligible. Almost all of the applied KCN was removed by rice seedlings and the metabolic rates were concentration dependent. Phyto-transport of K(3)Fe(CN)(6) was apparent, but appreciable amounts of cyanide were recovered in plant tissues. The metabolic rates of K(3)Fe(CN)(6) were also positively correlated to the concentrations supplied. Rice seedlings exposed to KCN showed a considerable increase in the CAS activity and roots had higher CAS activity than shoots, indicating that CAS plays an important role in the botanical assimilation of KCN. However, no measurable change of CAS activity in different parts of rice seedlings exposed to K(3)Fe(CN)(6) was detected, suggesting that K(3)Fe(CN)(6) is likely metabolized by rice directly through an unknown pathway rather than the beta-cyanoalanine pathway. PMID- 22068264 TI - Aza-boron-dipyrromethene dyes: TD-DFT benchmarks, spectral analysis and design of original near-IR structures. AB - The excited-state energies of aza-boron-dipyrromethene (Aza-BODIPY) derivatives are investigated with Time-Dependent Density Functional Theory (TD-DFT), with twin goals. On the one hand, a pragmatic, yet efficient, computational protocol is defined in order to reach rapidly semi-quantitative estimates of the lambda(max) of these challenging dyes. It turned out that a PCM-TD-BMK/6 311+G(2d,p)//PCM-PBE0/6-311G(2d,p) approach delivers appropriate lower bounds of the experimental results, despite the inherent limits of the vertical approximation. On the other hand, the method is applied to design new dyes absorbing in the near-IR. The spectral features of ca. 30 new compounds have been simulated in a systematic way, trying to efficiently combine several available synthetic strategies leading to significant bathochromic displacements. A series of dyes absorbing above 850 nm are proposed, illustrating that (relatively) fast theoretical calculations might be a useful pre-screening step preceding synthesis. PMID- 22068265 TI - Genetic determinants of Tibetan high-altitude adaptation. AB - Some highland populations have genetic adaptations that enable their successful existence in a hypoxic environment. Tibetans are protected against many of the harmful responses exhibited by non-adapted populations upon exposure to severe hypoxia, including elevated hemoglobin concentration (i.e., polycythemia). Recent studies have highlighted several genes subject to natural selection in native high-altitude Tibetans. Three of these genes, EPAS1, EGLN1 and PPARA, regulate or are regulated by hypoxia inducible factor, a principal controller of erythropoiesis and other organismal functions. Uncovering the molecular basis of hypoxic adaptation should have implications for understanding hematological and other adaptations involved in hypoxia tolerance. Because the hypoxia response involves a variety of cardiovascular, pulmonary and metabolic functions, this knowledge would improve our understanding of disease mechanisms and could ultimately be translated into targeted therapies for oxygen deprivation, cardiopulmonary and cerebral pathologies, and metabolic disorders such as diabetes and obesity. PMID- 22068266 TI - Effect of genu recurvatum on the anterior cruciate ligament-deficient knee during gait. AB - PURPOSE: This study aimed to investigate the effects of genu recurvatum, which is considered to carry a high risk for anterior cruciate ligament (ACL) injury, on healthy and post-ACL injury gait and lower extremity muscle strength. METHODS: Subjects were 36 patients with ACL-deficient knee and 40 healthy controls without pain or restricted range of motion of the lower extremity during gait. The knee joints of all subjects were examined; those with over 10 degrees hyperextension of both knees were defined as exhibiting genu recurvatum. On this basis, the subjects were further subdivided into two groups: with or without genu recurvatum. A three-dimensional motion analysis system and force plates were used for gait analysis. Isokinetic dynamometers were used to measure knee muscle strength. RESULTS: There were no differences in joint angles, joint moments, or components of ground reaction force during gait or in knee strength for the healthy control subjects with and without genu recurvatum. ACL-deficient subjects without genu recurvatum showed a decrease in knee angles during the stance phase and a decrease in extension moments during the early stance phase compared with ACL-deficient subjects with genu recurvatum and controls. In contrast, neither knee angles nor extension moments during the stance phase differed significantly between ACL-deficient subjects with genu recurvatum and controls. CONCLUSIONS: This study provides clinically relevant information regarding the effects of genu recurvatum on gait parameters. The results suggest that in ACL injuries, the presence of genu recurvatum alters gait pattern. Consideration of the presence of genu recurvatum would be useful during rehabilitation following ACL injuries or ACL reconstruction. LEVEL OF EVIDENCE: II. Prospective comparative study. PMID- 22068268 TI - Definition and classification of early osteoarthritis of the knee. AB - With the emerging interest in regenerative medicine and tissue engineering, new treatment modalities being developed for joint disorders including joint surface lesions and articular cartilage defects. The clinical outcome of these novel approaches appears rather unpredictable and is due to many reasons but definitely also linked to the patient profile. As a typical example, symptomatic articular cartilage lesions can be presented in an otherwise normal joint, or associated with several other joint tissue alterations including meniscal lesions and abnormalities of the underlying bone. The outcome of novel treatments may well be influenced by the status of the whole joint, and the potential to develop osteoarthritis. To better identify the patients at risk and responders to certain treatments, it is of use to define and most importantly classify patients with "early osteoarthritis". Here, classification criteria for this group of patients are presented, allowing a more defined and accurate inclusion in clinical trials in the future. PMID- 22068267 TI - Surgical treatment for early osteoarthritis. Part II: allografts and concurrent procedures. AB - Young patients with early osteoarthritis (OA) represent a challenging population due to a combination of high functional demands and limited treatment options. Conservative measures such as injection and physical therapy can provide short term pain relief but are only palliative in nature. Joint replacement, a successful procedure in the older population, is controversial in younger patients, who are less satisfied and experience higher failure rates. Therefore, while traditionally not indicated for the treatment of OA, cartilage repair has become a focus of increased interest due to its potential to provide pain relief and alter the progression of degenerative disease, with the hope of delaying or obviating the need for joint replacement. The field of cartilage repair is seeing the rapid development of new technologies that promise greater ease of application, less demanding rehabilitation and better outcomes. Concurrent procedures such as meniscal transplantation and osteotomy, however, remain of crucial importance to provide a normalized biomechanical environment for these new technologies. LEVEL OF EVIDENCE: Systematic review, Level II. PMID- 22068269 TI - The combination of microfracture and a cell-free polymer-based implant immersed with autologous serum for cartilage defect coverage. AB - PURPOSE: The purpose of this short-term pilot study was to determine the clinical and MRI outcome of a combination of microfracture with a cell-free polymer-based matrix for the treatment of cartilage defects in the knee. METHODS: The technique was used for treatment of symptomatic cartilage defects in the knee. Five patients were prospectively evaluated during 2 years with use of the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and the visual analog scale (VAS). MRI data were analyzed based on the original and modified MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) scoring system at 6, 12 and 24 months of follow-up. RESULTS: A gradual clinical improvement was observed during the follow-up. Adverse reactions to the matrix were not observed. The scaffold was firmly fixed with the use of bioresorbable pins. Both MOCART scoring systems revealed no significant deterioration or improvement in the repair tissue during the follow-up period. However, the majority of the patients exhibited subchondral lamina and bone changes. The formation of an intralesional osteophyte was observed in one case. CONCLUSIONS: The key finding in this study was that this procedure is safe for the treatment of cartilage defects in the knee. The patients showed a gradual clinical improvement postoperatively. Sixty percent (3/5) of the defects were adequately (complete or hypertrophic) filled with repair tissue at 2 years of follow-up. LEVEL OF EVIDENCE: IV. PMID- 22068270 TI - Keep the faith! Working with African American/black churches. PMID- 22068272 TI - State-mandated school-based BMI screening and parent notification: a descriptive case study. AB - To address childhood obesity, several states and local school districts across the United States have adopted body mass index (BMI) measurement initiatives. This descriptive case study explored psychosocial, environmental, and behavioral factors among parents of sixth-grade students who received BMI Health Letters (BMIHLs) in one Florida County. A nonexperimental postintervention design was employed to gather quantitative data via self-report Likert-type questionnaire. Participants were parents/guardians of sixth-grade students attending one Hillsborough County public middle school (n = 76). Results indicate three main findings: (a) most parents in this study (67.4%) who discussed the BMIHL with their child reported their child as "very" or "somewhat" uncomfortable with the discussion; (b) some parents of normal weight (NW) children responded by taking their child to a medical professional to control their weight; and (c) more parents of at risk of overweight/overweight (AR/OW) children (vs. NW) reported greater concern about their child's weight, using food restriction and physical activity to control their child's weight, and giving negative weight-related comments/behaviors. This case study illustrates the importance of adapting and tailoring state mandated BMIHLs for parents based on child's BMI status. PMID- 22068273 TI - A unifying hypothesis and a single name for a complex globally emerging infection: hantavirus disease. PMID- 22068274 TI - Laboratory evaluation of the ESwab transport system for the recovery of carbapenem-resistant Acinetobacter baumannii. AB - Microbiological surveillance for detection of carbapenem-resistant A. baumannii is important, but recovery of A. baumannii is inadequate. We studied A. baumannii recovery by a particular transport system that is possibly superior over standard swabs, using reference and clinical strains. First, the recovery rates relating to the various swabs were compared with regard to various combinations of transport times (0 h, 1 h, 24 h, 48 h), storage times (0 weeks, 1 week, 2 weeks, 4 weeks) and storage temperatures (4 degrees c,-80 degrees c) using live counts. Second, the recovery of different inocula of strains mixed with fecal microbiota was evaluated by plating on selective medium. The new transport system exhibited a decline of <3log10 under almost all conditions studied and performed better than standard swabs under several conditions. If plated on selective media, the new transport system performed well, even after prolonged transport or with a low inoculum, and its processing could be delayed by up to 2 weeks, especially if refrigerated. The new transport system may thus enhance A. baumannii surveillance. PMID- 22068275 TI - Molecular epidemiology and characterisation of MRSA isolates from Trinidad and Tobago. AB - Eighty methicillin-resistant Staphylococcus aureus (MRSA) isolates from three hospitals in Trinidad and Tobago were collected and genotyped using microarray hybridisation. They were found to belong to three distinct MRSA strains. Of the 80 isolates, 76 were assigned to ST239-MRSA-III. They were largely homogeneous, although some variations affected the presence of the enterotoxin A gene, as well as of resistance markers (mercury resistance operon, aadD, tet(K), qacA). The mupA gene conferring mupirocin resistance was found in 7.3% of isolates. One isolate was identified as CC5-MRSA-II and three isolates belonged to the Panton Valentine leukocidin (PVL)-positive ST8-MRSA-IV strain USA300. While community acquired MRSA strains are rare in Trinidad and Tobago, the vast majority of MRSA cases can be attributed to healthcare-associated strains. Thus, infection control procedures within medical facilities need to be revised and enforced. This could substantially reduce the burden of MRSA to healthcare in Trinidad and Tobago. PMID- 22068276 TI - Radioactive holmium acetylacetonate microspheres for interstitial microbrachytherapy: an in vitro and in vivo stability study. AB - PURPOSE: The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted. METHODS: HoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37 degrees C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS. RESULTS: After 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days. CONCLUSION: HoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment. PMID- 22068277 TI - Glucuronidation and methylation of procyanidin dimers b2 and 3,3"-di-o-galloyl-b2 and corresponding monomers epicatechin and 3-o-galloyl-epicatechin in mouse liver. AB - PURPOSE: The 3,3"-di-O-galloyl ester of procyanidin B2 (B2G2) is a component of grape seed extract that inhibits growth of human prostate carcinoma cell lines. In preparation for studies in mice, its hepatic metabolism was examined in vitro and compared to B2 and the corresponding monomers, epicatechin (EC) and 3-O galloyl-epicatechin (ECG). METHODS: Compounds were incubated with liver microsomes or cytosol containing cofactors for glucuronidation, sulfation or methylation, and products analyzed by liquid chromatography-mass spectrometry (LC MS). B2G2 was administered orally to mice and plasma analyzed by LC-MS for unmodified procyanidin and metabolites. RESULTS: Glucuronides and methyl ethers of B2 and B2G2 were formed in small amounts. In contrast, EC and ECG were largely or completely converted to glucuronides, sulfates and methyl ethers under the same incubation conditions. B2G2 given orally to mice was partially absorbed intact; no significant metabolites were detected in plasma. CONCLUSIONS: Glucuronidation and methylation of procyanidins B2 and B2G2 occurred but were minor processes in vitro. B2G2 was partially absorbed intact in mice after oral dosing and did not undergo significant metabolism. Unlike the flavanol monomers EC and ECG, therefore, B2G2 bioavailability should not be limited by metabolism. These results paved the way for ongoing pharmacokinetic and efficacy studies. PMID- 22068278 TI - Pharmacokinetic modeling to assess factors affecting the oral bioavailability of the lactone and carboxylate forms of the lipophilic camptothecin analogue AR-67 in rats. AB - PURPOSE: Camptothecin analogues are anticancer drugs effective when dosed in protracted schedules. Such treatment is best suited for oral formulations. AR-67 is a novel lipophilic analogue with potent efficacy in preclinical models. Here we assessed factors that may influence its oral bioavailability in rats. METHODS: Plasma pharmacokinetic (PK) studies were conducted following administration of AR 67 lactone or carboxylate doses alone or after pre-dosing with inhibitors of the efflux transporters P-gp and Bcrp. A population PK model that simultaneously fitted to oral and intravenous data was used to estimate the bioavailability (F) and clearance of AR-67. RESULTS: An inverse Gaussian function was used as the oral input into the model and provided the best fits. Covariate analysis showed that the bioavailability of the lactone, but not its clearance, was dose dependent. Consistent with this observation, the bioavailability of AR-67 increased when animals were pretreated orally with GF120918 or Zosuquidar. CONCLUSION: Absorption of AR-67 is likely affected by solubility of its lactone form and interaction with efflux pumps in the gut. AR-67 appears to be absorbed as the lactone form, most likely due to gastric pH favoring its formation and predominance. F increased at higher doses suggesting saturation of efflux mechanisms. PMID- 22068279 TI - Cellular reprogramming: a new technology frontier in pharmaceutical research. AB - Induced pluripotent stem cells via cellular reprogramming are now finding multiple applications in the pharmaceutical research and drug development pipeline. In the pre-clinical stages, they serve as model systems for basic research on specific diseases and then as key experimental tools for testing and developing therapeutics. Here we examine the current state of cellular reprogramming technology, with a special emphasis on approaches that recapitulate previously intractable human diseases in vitro. We discuss the technical and operational challenges that must be tackled as reprogrammed cells become incorporated into routine pharmaceutical research and drug discovery. PMID- 22068281 TI - Living life in the balance at midlife: lessons learned from mindfulness. AB - The purpose of this qualitative study was to describe the perceived effects of a Mindfulness-Based Stress Reduction (MBSR) Program on stress and quality of life of women in midlife. A total of 20 nurses, aged 45 to 55 years, who participated in a stress reduction course were contacted for interviews. A total of 9 nurses agreed to be interviewed. Content analysis was used to analyze these interviews. The five themes that emerged from the analysis were as follows: strengthening of interpersonal communication through social support, increased personal awareness through becoming more mindful and reflective, a spiritual awakening, effective ways of dealing with stress, and living life in balance by taking hold of one's life. This study increased the authors' understanding of effects/benefits, adherence, and application of MBSR techniques for women in midlife. It is concluded that MBSR may be a useful intervention for nurses in midlife to develop successful strategies for dealing with stress and to improve their quality of life. PMID- 22068280 TI - Use of artificial digestive systems to investigate the biopharmaceutical factors influencing the survival of probiotic yeast during gastrointestinal transit in humans. AB - PURPOSE: To evaluate the influence of the main biopharmaceutical factors on the viability of a new probiotic yeast strain, using dynamic in vitro systems simulating human gastric/small intestinal (TIM) and large intestinal (ARCOL) environments. METHODS: The viability of Saccharomyces cerevisiae CNCM I-3856 throughout the artificial digestive tract was determined by microbial counting. We investigated the effects of galenic formulation, food intake, dose, mode and frequency of administration on yeast survival rate. RESULTS: In both fasted and fed states, yeast viability in the upper digestive tract was significantly higher when the probiotic was administered in hydroxypropylmethylcellulose (HPMC) capsules compared to tablets. Food intake led to a delay in yeast release and a two-fold increase in strain survival. Whatever the dose, yeasts were particularly sensitive to the large intestinal environment. High concentrations of probiotic could only be maintained in the colon when it was inoculated twice a day over a 5 h-period. CONCLUSIONS: TIM and ARCOL are complementary in vitro tools relevant for screening purposes, supplying valuable information on the effects of galenic form, food intake and dose regimen on the viability of probiotics throughout the human digestive tract. PMID- 22068282 TI - Effects of informal caregivers on function of older adults in home health care. AB - This study aimed to examine the effects of informal caregivers on the functioning of older adults in home health care (HHC). The authors performed a secondary data analysis using the Outcome and Assessment Information Set of older adults (N = 8,750) who were admitted to a HHC agency from acute care hospitals. We conducted hierarchical multiple linear regression with functional dependence after a 60-day episode of formal HHC as an outcome variable. The older adults with informal caregivers showed less functional dependence at discharge (beta = -0.821, p = .027) than those without informal caregivers. Older adults who have a spouse (beta = -3.886, p < .001), offspring (beta = -3.614, p < .001), relative (beta = 4.360, p < .001), or nonrelative (beta = -4.977, p < .001) caregiver showed less functional dependence at discharge compared with those who had a paid caregiver when controlling for risk factors. PMID- 22068284 TI - Integrated analysis of multiple gene expression profiling datasets revealed novel gene signatures and molecular markers in nasopharyngeal carcinoma. AB - PURPOSE: To identify the novel gene signatures and molecular markers of nasopharyngeal carcinoma (NPC) by integrated bioinformatics analysis of multiple gene expression profiling datasets. EXPERIMENTAL DESIGN: Seven published gene expression profiling studies and one of our unpublished works were reanalyzed to identify the common significantly dysregulated (CSD) genes in NPC. Overrepresentation analysis of cytogenetic bands, Gene Ontology (GO) categories, pathways were used to explore CSD genes functionally associated with carcinogenesis. The protein expressions of selected CSD genes were examined by immunohistochemistry on tissue microarrays, and the correlations of their expressions with clinical outcomes were evaluated. RESULTS: Using the criteria (genes reported deregulated in more than one study), a total of 962 genes were identified as the CSD genes in NPC. Four upregulated (BUB1B, CCND2, CENPF, and MAD2L1) and two downregulated (LTF and SLPI) genes were markedly reported in six studies. The enrichments of chromosome aberrations were 2q23, 2q31, 7p15, 12q15, 12q22, 18q11, and 18q12 in upregulated genes and 14q32 and 16q13 in downregulated genes. The activated GO categories and pathways related to proliferation, adhesion, invasion, and downregulated immune response had been functionally associated with NPC. SLPI significantly downregulated in nasopharyngeal adenocarcinoma. Furthermore, the high expression of BUB1B or CENPF was associated with poor overall survival of patients. CONCLUSION: It was first clearly identified the dysregulated expression of BUB1B and SLPI in NPC tissues. IMPACT: Further studies of the CSD genes as gene signatures and molecular markers of NPC might improve the understanding of the disease and identify new therapeutic targets. PMID- 22068285 TI - Use of nonsteroidal anti-inflammatory drugs and survival following breast cancer diagnosis. AB - BACKGROUND: While there is accumulating evidence that use of nonsteroidal anti inflammatory drugs (NSAID) decreases breast cancer risk, little is known about the impact of NSAIDs on survival after breast cancer diagnosis. METHODS: We assessed whether recent, prediagnostic NSAID use and lifetime cumulative aspirin use before diagnosis were associated with survival among 1,024 women with incident, primary, invasive breast cancer. RESULTS: Recent prediagnostic use of aspirin, ibuprofen, and acetaminophen and lifetime use of aspirin up to diagnosis were not associated with either all-cause mortality or breast cancer-specific mortality. Neither dose nor frequency of use was associated with risk. Associations were not different for pre- and postmenopausal women. CONCLUSION: In our data, prediagnostic NSAID use and lifetime cumulative aspirin use were not associated with breast cancer survival. IMPACT: Our findings do not support a role of NSAIDs prior to diagnosis in breast cancer survival. PMID- 22068286 TI - Exercise effects on depressive symptoms in cancer survivors: a systematic review and meta-analysis. AB - BACKGROUND: Depression is a distressing side effect of cancer and its treatment. In the general population, exercise is an effective antidepressant. OBJECTIVE: We conducted a systematic review and meta-analysis to determine the antidepressant effect of exercise in cancer survivors. DATA SOURCES: In May 2011, we searched MEDLINE, PsycInfo, EMBASE, CINAHL, CDSR, CENTRAL, AMED, Biosis Previews, and Sport Discus and citations from relevant articles and reviews. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials (RCT) comparing exercise interventions with usual care in cancer survivors, using a self-report inventory or clinician rating to assess depressive symptoms, and reporting symptoms pre- and postintervention. STUDY APPRAISAL: Around 7,042 study titles were identified and screened, with 15 RCTs included. SYNTHESIS METHODS: Effect sizes (ES) were reported as mean change scores. The Q test was conducted to evaluate heterogeneity of ES. Potential moderator variables were evaluated with examination of scatter plots and Wilcoxon rank-sum or Kruskal-Wallis tests. RESULTS: The overall ES, under a random-effects model, was -0.22 (confidence interval, -0.43 to -0.09; P = 0.04). Significant moderating variables (ps < 0.05) were exercise location, exercise supervision, and exercise duration. LIMITATIONS: Only one study identified depression as the primary endpoint. CONCLUSIONS: Exercise has modest positive effects on depressive symptoms with larger effects for programs that were supervised or partially supervised, not conducted at home, and at least 30 minutes in duration. IMPACT: Our results complement other studies showing that exercise is associated with reduced pain and fatigue and with improvements in quality of life among cancer survivors. PMID- 22068287 TI - Long-term cancer risk among people diagnosed with AIDS during childhood. AB - BACKGROUND: Highly active antiretroviral therapy (HAART) results in partial immune restoration for people with AIDS, but its impact on cancer risk among children is unknown. METHODS: Data from the U.S. HIV/AIDS Cancer Match Study were used to evaluate cancer risk for people diagnosed with AIDS as children (diagnosed with AIDS at ages 0-14 years, during 1980-2007, followed for up to 10 years; N = 5,850). We calculated standardized incidence ratios (SIR) to compare cancer risk to the general population. Poisson regression evaluated changes in cancer incidence between the pre-HAART (1980-1995) and HAART eras (1996-2007). RESULTS: There were 106 cancers observed with significantly elevated risks for the two major AIDS-defining cancers: Kaposi sarcoma [KS; N = 20, SIR = 1,694; 95% confidence interval (CI), 986-2,712 and SIR = 1,146; 95% CI, 236-3,349] during the pre-HAART and HAART eras, respectively, and non-Hodgkin lymphoma (NHL; N = 64, SIR = 338; 95% CI, 242-458 and SIR = 116; 95% CI, 74-175). Incidence of both cancers declined 87% and 60%, respectively, in the HAART era (P < 0.05). Of non AIDS-defining cancers, leiomyosarcoma risk (N = 9) was elevated during both time periods (SIR = 863; 95% CI, 235-2,211 and SIR = 533; 95% CI, 173-1,243). CONCLUSION: People diagnosed with AIDS during childhood remain at elevated risk for KS, NHL, and leiomyosarcoma in the HAART era. Incidence of KS and NHL declined relative to widespread HAART use, but there was no change in the incidence of other cancers. IMPACT: People diagnosed with AIDS during childhood remain at elevated risk for certain cancers. Continued monitoring is warranted as this immunosuppressed population ages into adulthood where cancer risks generally increase. PMID- 22068288 TI - Patient activation increases colorectal cancer screening rates: a randomized trial among low-income minority patients. AB - BACKGROUND: Colorectal cancer (CRC) screening rates remain low among low-income and minority populations. The purpose of this study was to determine whether providing patients with screening information, activating them to ask for a screening test, and telephone barriers counseling improves CRC screening rates compared with providing screening information only. METHODS: Patients were randomized to CRC screening information plus patient activation and barriers counseling (n = 138) or CRC screening information (n = 132). Barriers counseling was attempted among activated patients if screening was not completed after one month. CRC screening test completion was determined by medical record review at two months after the medical visit. Logistic regression was used to determine whether activated patients were more likely to complete CRC screening, after adjustment for confounding factors (e.g., demographic characteristics and CRC knowledge). RESULTS: Patients were African American (72.2%), female (63.7%), had annual household incomes less than $20,000 (60.7%), no health insurance (57.0%), and limited health literacy skills (53.7%). In adjusted analyses, more patients randomized to the activation group completed a screening test (19.6% vs. 9.9%; OR = 2.35, 95% CI: 1.14-5.56; P = 0.020). In addition, more activated patients reported discussing screening with their provider (54.4% vs. 27.5%, OR = 3.29, 95% CI: 1.95-5.56; P < 0.001) and had more screening tests ordered (39.1% vs. 17.6%; OR = 3.40, 95% CI: 1.88-6.15; P < 0.001) compared with those in the control group. CONCLUSION: Patient activation increased CRC screening rates among low-income minority patients. IMPACT: Innovative strategies are still needed to increase CRC screening discussions, motivate providers to recommend screening to patients, as well as assist patients to complete ordered screening tests. PMID- 22068289 TI - Comparison of physical activity levels between cancer survivors and non-cancer participants in the 2009 BRFSS. AB - INTRODUCTION: The purpose of this study is to compare physical activity (PA) levels between cancer survivors and those without cancer diagnosis (non-cancer participants). METHODS: Using data from the 2009 Behavioral Risk Factor Surveillance System, we conducted secondary data analysis to compare PA between 31,078 cancer survivors with history of single-site cancer diagnosis at least 2 years prior to the survey, including cancer survivors of prostate [n = 2,951], female breast [n = 5,695], colon [n = 1,436], cervix [n = 2,211], endometrium [n = 1,080], and ovary [n = 732], and 235,351 non-cancer participants between 40 and 79 years of age. Self-reported PA and cancer history data were collected through telephone interviews. Weekly moderate- to vigorous-intensity PA levels were calculated in moderate-to-intensity physical activity equivalent (MIE). Least squares means of MIE were obtained from sex, age groups (40-64 years [middle aged] and 65-79 years [older]), and cancer site-specific multivariable linear regression models, adjusting for age, age(2), race/ethnicity, household income, and education. RESULTS: Prostate cancer survivors reported participating in approximately 20 min/week more MIE, compared to their non-cancer counterparts (P < 0.10 for the middle-aged group; P < 0.01 for the older group). Middle-aged cervical and endometrial cancer survivors reported approximately 10 min/week less MIE (P < 0.05 and P < 0.15, respectively). Adjusted means of MIE were not different between cancer survivors of colon, female breast, or ovary and non cancer participants. CONCLUSIONS: This study demonstrates higher PA levels among prostate cancer survivors and lower PA levels among middle-aged cervical and endometrial cancer survivors, compared to sex- and age group-matched general populations. PMID- 22068290 TI - Terminalia gum as a directly compressible excipient for controlled drug delivery. AB - The exudates from the incised trunk of Terminalia randii has been evaluated as controlled release excipient in comparison with xanthan gum and hydroxypropylmethylcellulose (HPMC) using carvedilol (water insoluble) and theophylline (water soluble) as model drugs. Matrix tablets were prepared by direct compression and the effects of polymer concentration and excipients-spray dried lactose, microcrystalline cellulose and dicalcium phosphate dihydrate on the mechanical (crushing strength (CS) friability (F) and crushing strength friability ratio (CSFR)) and drug release properties of the matrix tablets were evaluated. The drug release data were fitted into different release kinetics equations to determine the drug release mechanism(s) from the matrix tablets. The results showed that the CS and CSFR increased with increase in polymer concentration while F decreased. The ranking of CS and CSFR was HPMC > terminalia > xanthan while the ranking was reverse for F. The ranking for t(25) (i.e. time for 25% drug release) at a polymer concentration of 60% was xanthan > terminalia = HPMC. The dissolution time, t(25), of theophylline matrices was significantly lower (p < 0.001) than those of carvedilol matrix tablets. Drug release from the matrices was by swelling, diffusion and erosion. The mechanical and drug release properties of the tablets were significantly (p < 0.05) dependent on the type and concentration of polymer and excipients used with the release mechanisms varying from Fickian to anomalous. Terminalia gum compared favourably with standard polymers when used in controlled release matrices and could serve as a suitable alternative to the standard polymers in drug delivery. PMID- 22068291 TI - Effect of sorbed water on disintegrant performance of four brands of Polacrilin Potassium NF. AB - Polacrilin Potassium NF is a commonly used weak cation exchange resin disintegrant in pharmaceutical tablets. The objective of this research was to evaluate the effects of sorbed moisture on physical characteristics and disintegrant performance of four brands of Polacrilin Potassium NF. The disintegrants were stored in five different relative humidity chambers and their dynamic vapor adsorption-desorption analysis, effect of moisture on their compressibility, compactability, particle size, morphology, water uptake rate, and disintegration ability were studied. Moisture seemed to plasticize the disintegrants, reducing their yield pressures. However, certain optimum amount of moisture was found to be useful in increasing the compactablity of the tablets containing disintegrants. The tablets, however, lost their tensile strengths beyond this optimum moisture content. Moisture caused two brands of the disintegrants to swell; however, two other brands aggregated upon exposure to moisture. Swelling without aggregation increased the water uptake, and in turn the disintegrant performance. However, aggregation probably reduced the porosities of the disintegrants, reducing their water uptake rate and disintegrant performance. Different brands of Polacrilin Potassium NF differed in the abilities to withstand the effects of moisture on their functionality. Effect of moisture on disintegrant performance of Polacrilin Potassium NF needs to be considered before its use in tablets made by wet granulation. PMID- 22068292 TI - Parents' Experiences of Discrimination and Family Relationship Qualities: The Role of Gender. AB - Mothers and fathers in 156 African American families reported on racial discrimination experiences, gendered traits, and warmth and conflict in family relationships. Discrimination was linked with relationship quality, but links differed for mothers and fathers. More expressive parents and less instrumental fathers had more positive relationships in the face of discrimination, but for more instrumental fathers, discrimination-relationship quality links were negative. Findings imply consideration of sociocultural and individual characteristics for family relationships. PMID- 22068294 TI - Simultaneous electrochemical immunoassay of three liver cancer biomarkers using distinguishable redox probes as signal tags and gold nanoparticles coated carbon nanotubes as signal enhancers. AB - A novel strategy for simultaneous determination of three liver cancer biomarkers based on three redox labels with distinct voltammetric peaks was described. Gold nanoparticles coated carbon nanotubes were used as carriers to immobilize redox probes labeled antibodies and to amplify the signals. PMID- 22068299 TI - Cyclohexyl "base pairs" stabilize duplexes and intensify pyrene fluorescence by shielding it from natural base pairs. AB - In this study, we investigated the stability and structure of artificial base pairs that contain cyclohexyl rings. The introduction of a single pair of isopropylcyclohexanes into the middle of DNA slightly destabilized the duplex. Interestingly, as the number of the "base pairs" increased, the duplex was remarkably stabilized. A duplex with six base pairs was even more stable than one containing six A-T pairs. Thermodynamic analysis revealed that changes in entropy and not enthalpy contributed to duplex stability, demonstrating that hydrophobic interactions between isopropyl groups facilitated the base pairing, and thus stabilized the duplex. NOESY of a duplex containing an isopropylcyclohexane methylcyclohexane pair unambiguously demonstrated its "pairing" in the duplex because distinct NOEs between the protons of cyclohexyl moieties and imino protons of both of the neighboring natural base pairs were observed. CD spectra of duplexes tethering cyclohexyl moieties also showed a positive-negative couplet that is characteristic of the B-form DNA duplex. Taken together, these results showed that cyclohexyl moieties formed base pairs in the DNA duplex without severely disturbing the helical structure of natural DNA. Next, we introduced cyclohexyl base pairs between pyrene and nucleobases as an "insulator" that suppresses electron transfer between them. We found a massive increase in the quantum yield of pyrene due to the efficient shielding of pyrene from nucleobases. The cyclohexyl base pairs reported here have the potential to prepare highly fluorescent labeling agents by multiplying fluorophores and insulators alternately into DNA duplexes. PMID- 22068300 TI - Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. AB - OBJECTIVE: Higher levels of physical activity have been consistently associated with a decreased risk of colon cancer, but not rectal cancer, in Western populations. The present study systematically evaluated epidemiologic evidence on the association between physical activity and colorectal cancer risk among the Japanese population. METHODS: Original data were obtained from MEDLINE searched using PubMed or from searches of the Ichushi database, complemented by manual searches. The associations were evaluated based on the strength of evidence, the magnitude of association and biologic plausibility. RESULTS: Two cohort studies and six case-control studies were identified. A weak to strong protective association between physical activity and colon cancer risk was observed in both cohort studies, showing a graded relationship, and among the majority of case control studies, with some showing a dose-response relationship. The association observed in cohort studies was more consistent and stronger in men than in women and for proximal colon cancer than for distal colon cancer. A protective association with rectal cancer was found only in case-control studies, but the evidence was less consistent and weaker than that observed for colon cancer. CONCLUSIONS: Physical activity probably decreases the risk of colorectal cancer among the Japanese population. More specifically, the evidence for the colon is probable, whereas that for the rectum is insufficient. PMID- 22068306 TI - Late onset of skin manifestations in Birt-Hogg-Dube syndrome with FLCN mutation p.W260X. PMID- 22068307 TI - Highly regioselective Lewis acid-catalyzed [3+2] cycloaddition of alkynes with donor-acceptor oxiranes by selective carbon-carbon bond cleavage of epoxides. AB - A novel, efficient, highly regioselective Sc(OTf)(3)-catalyzed [3+2] cycloaddition of electron-rich alkynes with donor-acceptor oxiranes via highly chemoselective C-C bond cleavage under mild conditions was developed. PMID- 22068308 TI - Antibiotic resistance really starts to hurt. PMID- 22068309 TI - Nitron: a stable N-heterocyclic carbene that has been commercially available for more than a century. AB - The analytical reagent Nitron is a mesoionic compound whose structure consists of a cationic triazolium unit with an anionic PhN substituent. We provide clear evidence for the existence of a singlet diaminocarbene tautomer whose structure is composed of a 1,2,4-triazol-5-ylidene unit bearing an NHPh substituent. PMID- 22068310 TI - Identification of heavy metal pollutants using multivariate analysis and effects of land uses on their accumulation in urban soils in Beijing, China. AB - In order to evaluate the current state of the environmental quality of soils in Beijing, we investigated contents of 14 metals in Beijing urban soils inside the 5th ring road by even grids sampling. Statistic analyses were conducted to identify possible heavy metal pollutants, as well as the effects of land uses on their accumulation. Our results revealed that the urban soils in Beijing were contaminated by Cd, Pb, Cu, and Zn. Land uses and urbanization ages affected the accumulation of the four heavy metals in soils significantly. Soils in industrial areas have the highest average Cu and Zn contents, while Pb contents in park areas and Cd in agricultural areas are the highest. The accumulations of Pb and Zn in urban soils increase significantly with sampling plots approaching the city center. And Pb, Cd, and Zn contents in soils in traffic areas also tend to increase in the city center. However, residential areas have the lowest contents of all the four heavy metals. PMID- 22068311 TI - Heavy metal assessment using geochemical and statistical tools in the surface sediments of Vembanad Lake, Southwest Coast of India. AB - The geochemical distribution and enrichment of ten heavy metals in the surface sediments of Vembanad Lake, southwest coast of India was evaluated. Sediment samples from 47 stations in the Lake were collected during dry and wet seasons in 2008 and examined for heavy metal content (Al, Fe, Mn, Cr, Zn, Ni, Pb, Cu, Co, Cd), organic carbon, and sediment texture. Statistically significant spatial variation was observed among all sediment variables, but negligible significant seasonal variation was observed. Correlation analysis showed that the metal content of sediments was mainly regulated by organic carbon, Fe oxy-hydroxides, and grain size. Principal component analysis was used to reduce the 14 sediment variables into three factors that reveal distinct origins or accumulation mechanisms controlling the chemical composition in the study area. Pollution intensity of the Vembanad Lake was measured using the enrichment factor and the pollution load index. Severe and moderately severe enrichment of Cd and Zn in the north estuary with minor enrichment of Pb and Cr were observed, which reflects the intensity of the anthropogenic inputs related to industrial discharge into this system. The results of pollution load index reveal that the sediment was heavily polluted in northern arm and moderately polluted in the extreme end and port region of the southern arm of the lake. A comparison with sediment quality guideline quotient was also made, indicating that there may be some ecotoxicological risk to benthic organisms in these sediments. PMID- 22068312 TI - Determination of three alkylphenol isomers in various water samples using a new HPLC method based on a duet stationary phase. AB - The level of three alkylphenols (APs) 4-nonylphenol, 4-octylphenol and 4-tert octylphenol was monitored in various water samples using a new developed and validated HPLC method. The HPLC method employed a column with a mixed-mode stationary phase (C18/SCX) using a mobile phase of water to methanol = 15:85 (v/v) delivered at a flow rate of 1 mL/min at room temperature. Both diode array, DAD and fluorescence, FLD detectors were employed. The method is linear when APs concentration ranged from 0.025 to 0.5 MUg/mL with a DAD detection at 279 nm and between 0.0008 and 0.1 MUg/mL when the detection was made by FLD (excitation at 220 nm, emission at 315 nm). The limit of detection and limit of quantitation for alkylphenols were found to be 5 and 15 ng/mL, respectively (detection by DAD). The method was employed with good results for the determination of APs in the presence of polycyclic aromatic hydrocarbons in various water samples. PMID- 22068313 TI - Principles for the monitoring and evaluation of wetland extent, condition and function in Australia. AB - The monitoring of resource condition is receiving renewed attention across several levels of government in Australia. This interest is linked to substantial investment in environmental remediation and aquatic ecosystem restoration in particular. In this context, it is timely to consider principles which ought to guide the development and implementation of monitoring programmes for wetland ecosystems. A framework is established which places monitoring in the context of the strategic adaptive management of wetlands. This framework requires there has to be clear goals for the extent and condition of the resource, with these goals being defined within thresholds of acceptable variability. Qualitative and, where possible, quantitative conceptual models linking management interventions to management goals should be the basis of indicator selection and assessment. The intensity of sampling ought to be informed by pilot surveys of statistical power in relation to the thresholds of acceptable variability identified within the management plan. PMID- 22068314 TI - Removal of phenols and other pollutants from different landfill leachates using powdered activated carbon supplemented SBR technology. AB - In this research, two types of sequencing batch reactors (SBRs) with 8 h of cycle times, namely non-powdered activated carbon (NPAC-SBR) and powdered activated carbon (PAC-SBR), were used for the treatment of raw leachates at Kulim and Pulau Burung landfill sites. To test the performance of SBRs, phenols, total iron, zinc, ammonia, nitrite, nitrate, color, suspended solids, chemical oxygen demand, biochemical oxygen demand, and total dissolved salts removal efficiencies and sludge volume index (SVI) were studied at both sites. The rates of phenols removal, for instance in NPAC-SBRs and PAC-SBRs at Kulim, were 25% and 55%, respectively, whereas those at Pulau Buring were 94.81% and 97.75%, respectively. PAC as adsorbent in PAC-SBRs enhanced the removal efficiencies of the aforementioned pollutants from leachates at both sites. In addition, PAC as adsorbent decreased the SVI values at Kulim (59.7 mL/g) and Pulau Burung (91.4 mL/g) leachates and improved the nitrification and denitrification processes. PMID- 22068315 TI - Abundance versus presence/absence data for modelling fish habitat preference with a genetic Takagi-Sugeno fuzzy system. AB - This study compared the accuracy of fuzzy habitat preference models (FHPMs) and habitat preference curves (HPCs) obtained from the FHPMs in order to assess the effect of two types of data [log-transformed fish population density (LOG) and presence-absence (P/A) data] on the habitat preference evaluation of Japanese medaka (Oryzias latipes). Three independent data sets were prepared for each type of data. The results differed according to the data sets and the types of data used. The HPCs showed a similar trend, whilst the degrees of preference were different. The model accuracy also differed according to the data sets used. Although almost no statistical difference was observed, on average, the P/A-based models showed a better performance according to the threshold-independent performance measures, whilst the LOG-based models showed better performance in predicting absence of the fish. These results can be explained partly from the different shapes of HPCs. This case study of Japanese medaka demonstrated the effect of different types of data on habitat preference evaluation. Further studies should build on the present finding and evaluate the effects of data characteristics such as the size of data sets and the prevalence for better understanding and reliable assessment of the habitat for target species. PMID- 22068316 TI - Distribution behavior and carcinogenic level of some polycyclic aromatic hydrocarbons in roadside soil at major traffic intercepts within a developing city of India. AB - A study of polycyclic aromatic hydrocarbons (PAHs) pollution in roadside soil was conducted at a developing city locations of Jalandhar (Punjab), India in winter season to ascertain the contamination levels and their distribution behavior in roadside soil. PAHs concentration level of ten locations was measured at 1, 2, and 3 m distances from roadside soil covering all the major traffic intercepts within a city. Samples were extracted in acetone and dichloromethane (1:1) using soxhlet extraction. The extracts were filtered on a silica gel micro column to remove impurities and eluate was subjected to GC-FID. The total average PAHs concentration (city average) was found to be 4.04 MUg g(-1), whereas the concentration of 16 individual PAHs was found to vary between 0.008 and 28.4 MUg g(-1). The average concentration of noncarcinogenic and carcinogenic PAHs in all the samples was 2.17 and 6.41 MUg g(-1) (ratio 1:2.95). The concentration of five ringed PAHs was found to be 45% to 60%, whereas two ringed PAHs were found to be in the range from 0.28% to 0.56% in all most all locations. The average highest PAHs concentration for any individual location was found as 12.23 MUg g(-1) at DAV Chowk at 1 m distance and minimum concentration was 0.98 MUg g(-1) at Maqsuda Chowk at 1 m distance from roadside. DiB (ah) A was the individual PAHs found in highest concentration in all the intercepts ranging between 1.26 and 28 MUg g( 1). At most of the city intercepts, total carcinogenic PAHs concentration was found to range from 60% to 80% in comparison to noncarcinogenic PAHs (20%-40%) at most of the intercepts. The pollution level our study was compared with other cities of India/worldwide. PMID- 22068317 TI - Uncertain spatial reasoning of environmental risks in GIS using genetic learning algorithms. AB - Modeling the impact of air pollution is one of the most important approaches for managing damages to the ecosystem. This problem can be solved by sensing and modeling uncertain spatial behaviors, defining topological rules, and using inference and learning capabilities in a spatial reasoning system. Reasoning, which is the main component of such complex systems, requires that proper rules be defined through expert judgments in the knowledge-based part. Use of genetic fuzzy capabilities enables the algorithm to learn and be tuned to proper rules in a flexible manner and increases the preciseness and robustness of operations. The main objective of this paper was to design and evaluate a spatial genetic fuzzy system, with the goal of assessing environmental risks of air pollution due to oil well fires during the Persian Gulf War. Dynamic areas were extracted and monitored through images from NOAA, and the data were stored in an efficient spatial database. Initial spatial knowledge was determined by expert consideration of the application characteristics, and the inference engine was performed with genetic learning (GL) algorithms. Finally, GL (0.7 and 0.03), GL (0.7 and 0.08), GL (0.98 and 0.03), GL (0.98 and 0.08), and Cordon learning methods were evaluated with test and training data related to samples extracted from Landsat thematic mapper satellite images. Results of the implementation showed that GL (0.98, 0.03) was more precise than the other methods for learning and tuning rules in the concerned application. PMID- 22068318 TI - Redox switching and oxygen evolution at oxidized metal and metal oxide electrodes: iron in base. AB - Outstanding issues regarding the film formation, redox switching characteristics and the oxygen evolution reaction (OER) electrocatalytic behaviour of multicycled iron oxyhydroxide films in aqueous alkaline solution have been revisited. The oxide is grown using a repetitive potential multicycling technique, and the mechanism of the latter hydrous oxide formation process has been discussed. A duplex layer model of the oxide/solution interphase region is proposed. The acid/base behaviour of the hydrous oxide and the microdispersed nature of the latter material has been emphasised. The hydrous oxide is considered as a porous assembly of interlinked octahedrally coordinated anionic metal oxyhydroxide surfaquo complexes which form an open network structure. The latter contains considerable quantities of water molecules which facilitate hydroxide ion discharge at the metal site during active oxygen evolution, and also charge compensating cations. The dynamics of redox switching has been quantified via analysis of the cyclic voltammetry response as a function of potential sweep rate using the Laviron-Aoki electron hopping diffusion model by analogy with redox polymer modified electrodes. Steady state Tafel plot analysis has been used to elucidate the kinetics and mechanism of oxygen evolution. Tafel slope values of ca. 60 mV dec(-1) and ca. 120 mV dec(-1) are found at low and high overpotentials respectively, whereas the reaction order with respect to hydroxide ion activity changes from ca. 3/2 to ca. 1 as the potential is increased. These observations are rationalised in terms of a kinetic scheme involving Temkin adsorption and the rate determining formation of a physisorbed hydrogen peroxide intermediate on the oxide surface. The dual Tafel slope behaviour is ascribed to the potential dependence of the surface coverage of adsorbed intermediates. PMID- 22068319 TI - Variation in seedling freezing response is associated with climate in Larrea. AB - Variation in freezing severity is hypothesized to have influenced the distribution and evolution of the warm desert evergreen genus Larrea. If this hypothesis is correct, performance and survival of species and populations should vary predictably along gradients of freezing severity. If freezing environment changes in the future, the ability of Larrea to adapt will depend on the structure of variation for freezing resistance within populations. To test whether freezing responses vary among and within Larrea populations, we grew maternal families of seedlings from high and low latitude L. divaricata and high latitude L. tridentata populations in a common garden. We measured survival, projected plant area and dark-adapted chlorophyll fluorescence (F (v) /F (m)) before and after cold acclimation and for 2 weeks following a single freeze. We detected significant variation in freezing resistance among species and populations. Maternal family lines differed significantly in their responses to cold acclimation and/or freezing for two out of the three populations: among L. tridentata maternal families and among low latitude L. divaricata maternal families. There were no significant differences across maternal families of high latitude L. divaricata. Our results indicate that increased freezing resistance in high latitude populations likely facilitated historical population expansion of both species into colder climates, but this may have occurred to a greater extent for L. tridentata than for L. divaricata. Differences in the structure of variation for cold acclimation and freezing responses among populations suggest potential differences in their ability to evolve in response to future changes in freezing severity. PMID- 22068320 TI - Anxiety and depression associated with incontinence in middle-aged women: a large Norwegian cross-sectional study. AB - INTRODUCTION AND HYPOTHESIS: Several studies have indicated depression and anxiety to be associated with urinary incontinence (UI), however, the strength of the associations varies widely. The objective of this study was to determine these associations in a large survey. METHODS: In a cross-sectional population based survey study, we analysed questionnaire data on UI, depression and anxiety from 5,321 women between 40 and 44 years. A multivariate logistic regression model was used to predict the odds of having high levels of anxiety and depression among women with UI of different types and severities. RESULTS: Among women with UI, the adjusted OR for depression was 1.64 (95% CI, 1.32-2.04) and for anxiety 1.59 (95% CI, 1.36-1.86) compared with women without UI. CONCLUSION: UI was associated with both anxiety and depression in middle-aged women, with the strongest associations for mixed and urgency UI. PMID- 22068321 TI - Traditional native tissue versus mesh-augmented pelvic organ prolapse repairs: providing an accurate interpretation of current literature. AB - The objective of this paper was to review the literature on pelvic organ prolapse (POP) and compare the success of traditional/native tissue versus mesh-augmented repairs. A comprehensive literature review was performed using PubMed and bibliography searches to compare the anatomic success rates of native tissue (NT) and mesh-augmented (MA) prolapse repairs and to analyze outcome measures used to report success rates. Articles were included if anatomic outcomes were stated for the specific compartment of interest and included both prospective and retrospective studies. The published success rates for NT repairs versus MA repairs by anterior, posterior, or apical compartments are reported. When continence is used as the primary outcome measure, anterior NT has a success rate of 54%. Anterior NT success is as low as 30% in some studies, but generally is 88 97% when prolapse is the primary outcome particularly if apical support is included. This compares to the 87-96% success reported for anterior MA. Posterior NT success is 54-81%, which is lower than the 92-97% reported for posterior MA when prolapse is the outcome measure. The success rates for apical NT are 97-98% for uterosacral ligament suspension and 96% for sacrospinous ligament suspension, which compare favorably to sacrocolpopexy (91-100%). There are some differences in the complications reported for NT and MA. The rate of complications is approximately 8% for NT and is reported at 0-19% for MA. The higher rate for MA is largely due to mesh erosion/exposure. When similar outcome measures are compared, the published anatomic success rates of POP of anterior and apical compartmental surgery are similar for NT and MA repairs. There may be a higher rate of complications noted for mesh implantation. POP surgery is complex, and both NT and MA techniques require skills to perform proper compartmental reconstruction. An understanding of the published literature and knowledge of individual surgeon factors are important in deciding which surgical approach to use and how to best counsel patients during informed consent. PMID- 22068322 TI - 3D analysis of cystoceles using magnetic resonance imaging assessing midline, paravaginal, and apical defects. AB - INTRODUCTION AND HYPOTHESIS: This study assesses relative contributions of "midline defects" (widening of the vagina) and "paravaginal defects" (separation of the lateral vagina from the pelvic sidewall). METHODS: Ten women with anterior predominant prolapse and ten with normal support underwent pelvic MR imaging. 3-D models of the anterior vaginal wall (AVW) were generated to determine locations of the lateral AVW margin, vaginal width, and apical position. RESULTS: The lateral AVW margin was farther from its normal position in cases than controls throughout most of the vaginal length, most pronounced midvagina (effect sizes, 2.2-2.8). Vaginal widths differed in the midvagina with an effect size of 1.0. Strong correlations between apical and paravaginal support were evident in mid- and upper vagina (r = 0.77-0.93). CONCLUSIONS: Changes in lateral AVW location were considerably greater than changes in vaginal width in cases vs controls, both in number of sites affected and effect sizes. These "paravaginal defects" are highly correlated with apical descent. PMID- 22068323 TI - TGF-beta 1 is a potential regulator of vaginal tropoelastin production. AB - INTRODUCTION AND HYPOTHESIS: Our aims were to correlate transforming growth factor (TGF)-beta1 and elastin mRNA expression in the vagina of women and to measure the effects of TGF-beta1 on vaginal smooth muscle cell (SMC) proliferation and tropoelastin production. METHODS: Vaginal walls were sampled in women (n = 20). TGF-beta1 and elastin mRNA expression was assessed by RT-PCR. SMC cultures were performed from vaginal wall biopsies. SMC were incubated with TGF beta1, and cell proliferation was assessed by MTT-assay. Tropoelastin production was measured by the Fastin Elastin Assay. RESULTS: There was a significant positive correlation between TGF-beta1 and elastin mRNA (r = 0.784, P < 0.01). SMC proliferation was significantly increased by 10 ng/mL TGF-beta1 [relative cell number, mean +/- SD, 198% +/- 32% of control (P = 0.01)]. Tropoelastin production was significantly increased by TGF-beta1 [mean +/- SD, 645% +/- 180% of control (P = 0.01)]. CONCLUSIONS: There is a positive correlation between TGF beta1 and elastin mRNA expression in the vaginal wall. In vitro, TGF-beta1 increases vaginal tropoelastin production in vaginal SMC. PMID- 22068324 TI - Suburethral sling in autoimmune patients: complications, quality of life, and success rate. AB - INTRODUCTION AND HYPOTHESIS: Suburethral sling procedures are a mainstay for the surgical treatment of stress urinary incontinence (SUI). The interaction between the sling and the host is fundamental for the success of the procedure. Patients affected by autoimmune disease present with an overactive immune system; this should theoretically increase rejection risk. METHODS: The data from 19 autoimmune patients affected by SUI were retrospectively collected. Primary outcome consisted of evaluating whether tape-related complications may occur more frequently. Secondary outcome measures were assessment of objective and subjective cure of SUI. Changes from baseline were analyzed using the Mann Whitney and Fisher tests. RESULTS: Success rate, evaluated at 12-month follow-up, was 89.5%. No tape erosion or urinary retention was observed; chronic pelvic pain and dyspareunia rates were 5.26% and 15.4%, respectively. One patient developed de novo urgency. CONCLUSIONS: According to our experience, the suburethral sling is a safe procedure with low complication rates comparable to those reported in the literature. PMID- 22068325 TI - Airlift column photobioreactors for Porphyridium sp. culturing: part I. effects of hydrodynamics and reactor geometry. AB - Photosynthetic microorganisms have been attracting world attention for their great potential as renewable energy sources in recent years. Cost effective production in large scale, however, remains a major challenge to overcome. It is known to the field that turbulence could help improving the performance of photobioreactors due to the so-called flashing light effects. Better understanding of the multiphase fluid dynamics and the irradiance distribution inside the reactor that cause the flashing light effects, as well as quantifying their impacts on the reactor performance, thus, are crucial for successful design and scale-up of photobioreactors. In this study, a species of red marine microalgae, Porphyridium sp., was grown in three airlift column photobioreactors (i.e., draft tube column, bubble column, and split column). The physical properties of the culture medium, the local fluid dynamics and the photobioreactor performances were investigated and are reported in this part of the manuscript. Results indicate that the presence of microalgae considerably affected the local multiphase flow dynamics in the studied draft tube column. Results also show that the split column reactor works slightly better than the draft tube and the bubble columns due to the spiral flow pattern inside the reactor. PMID- 22068326 TI - Pharmacist interventions on antibiotic use in inpatients with respiratory tract infections in a Chinese hospital. AB - OBJECTIVE: To evaluate the impact of pharmacist interventions on antibiotic use in inpatients with respiratory tract infections in a tertiary hospital in China. METHOD: Two independent respiratory wards were randomized into control and intervention group. Between July 2009 and April 2010, all inpatients diagnosed with respiratory tract infections were enrolled. Pharmacist interventions were performed on the physicians in the intervention group. The total cost of hospitalization, cost of antibiotics, length of hospital stay and the scores of 6 items of inappropriate antibiotic use (including indication, choice, dosage, dosing schedule, duration and conversion) were analyzed. RESULTS: The total costs of hospitalization in the intervention group were significant lower compared to the control group ($1442.3 +/- 684.9 vs. $1729.6 +/- 773.7, P < 0.001), as well as the cost of antibiotics ($832.0 +/- 373.0 vs. $943.9 +/- 412.0, P = 0.01), and the patients required shorter length of hospital stay (14.2 +/- 6.2 vs. 15.8 +/- 6.0 days, P = 0.03). The scores with respect to the 6 items of inappropriate antibiotic use were all lower in the intervention group than in the control group. CONCLUSIONS: Pharmacist interventions, interacted directly with the physicians at ward level, could play an important role in optimizing antibiotic use, thus lead to the reduction in patients' length of hospital stay and health care cost. PMID- 22068327 TI - Systematic exploration of synergistic drug pairs. AB - Drug synergy allows a therapeutic effect to be achieved with lower doses of component drugs. Drug synergy can result when drugs target the products of genes that act in parallel pathways ('specific synergy'). Such cases of drug synergy should tend to correspond to synergistic genetic interaction between the corresponding target genes. Alternatively, 'promiscuous synergy' can arise when one drug non-specifically increases the effects of many other drugs, for example, by increased bioavailability. To assess the relative abundance of these drug synergy types, we examined 200 pairs of antifungal drugs in S. cerevisiae. We found 38 antifungal synergies, 37 of which were novel. While 14 cases of drug synergy corresponded to genetic interaction, 92% of the synergies we discovered involved only six frequently synergistic drugs. Although promiscuity of four drugs can be explained under the bioavailability model, the promiscuity of Tacrolimus and Pentamidine was completely unexpected. While many drug synergies correspond to genetic interactions, the majority of drug synergies appear to result from non-specific promiscuous synergy. PMID- 22068328 TI - Mapping the interaction of Snf1 with TORC1 in Saccharomyces cerevisiae. AB - Nutrient sensing and coordination of metabolic pathways are crucial functions for all living cells, but details of the coordination under different environmental conditions remain elusive. We therefore undertook a systems biology approach to investigate the interactions between the Snf1 and the target of rapamycin complex 1 (TORC1) in Saccharomyces cerevisiae. We show that Snf1 regulates a much broader range of biological processes compared with TORC1 under both glucose- and ammonium-limited conditions. We also find that Snf1 has a role in upregulating the NADP(+)-dependent glutamate dehydrogenase (encoded by GDH3) under derepressing condition, and therefore may also have a role in ammonium assimilation and amino-acid biosynthesis, which can be considered as a convergence of Snf1 and TORC1 pathways. In addition to the accepted role of Snf1 in regulating fatty acid (FA) metabolism, we show that TORC1 also regulates FA metabolism, likely through modulating the peroxisome and beta-oxidation. Finally, we conclude that direct interactions between Snf1 and TORC1 pathways are unlikely under nutrient-limited conditions and propose that TORC1 is repressed in a manner that is independent of Snf1. PMID- 22068329 TI - Algorithms in nature: the convergence of systems biology and computational thinking. AB - Computer science and biology have enjoyed a long and fruitful relationship for decades. Biologists rely on computational methods to analyze and integrate large data sets, while several computational methods were inspired by the high-level design principles of biological systems. Recently, these two directions have been converging. In this review, we argue that thinking computationally about biological processes may lead to more accurate models, which in turn can be used to improve the design of algorithms. We discuss the similar mechanisms and requirements shared by computational and biological processes and then present several recent studies that apply this joint analysis strategy to problems related to coordination, network analysis, and tracking and vision. We also discuss additional biological processes that can be studied in a similar manner and link them to potential computational problems. With the rapid accumulation of data detailing the inner workings of biological systems, we expect this direction of coupling biological and computational studies to greatly expand in the future. PMID- 22068330 TI - Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome. AB - Genetic analysis in Drosophila melanogaster has been widely used to identify a system of genes that control cell growth in response to insulin and nutrients. Many of these genes encode components of the insulin receptor/target of rapamycin (InR/TOR) pathway. However, the biochemical context of this regulatory system is still poorly characterized in Drosophila. Here, we present the first quantitative study that systematically characterizes the modularity and hormone sensitivity of the interaction proteome underlying growth control by the dInR/TOR pathway. Applying quantitative affinity purification and mass spectrometry, we identified 97 high confidence protein interactions among 58 network components. In all, 22% of the detected interactions were regulated by insulin affecting membrane proximal as well as intracellular signaling complexes. Systematic functional analysis linked a subset of network components to the control of dTORC1 and dTORC2 activity. Furthermore, our data suggest the presence of three distinct dTOR kinase complexes, including the evolutionary conserved dTTT complex (Drosophila TOR, TELO2, TTI1). Subsequent genetic studies in flies suggest a role for dTTT in controlling cell growth via a dTORC1- and dTORC2-dependent mechanism. PMID- 22068331 TI - Deep proteome and transcriptome mapping of a human cancer cell line. AB - While the number and identity of proteins expressed in a single human cell type is currently unknown, this fundamental question can be addressed by advanced mass spectrometry (MS)-based proteomics. Online liquid chromatography coupled to high resolution MS and MS/MS yielded 166 420 peptides with unique amino-acid sequence from HeLa cells. These peptides identified 10 255 different human proteins encoded by 9207 human genes, providing a lower limit on the proteome in this cancer cell line. Deep transcriptome sequencing revealed transcripts for nearly all detected proteins. We calculate copy numbers for the expressed proteins and show that the abundances of > 90% of them are within a factor 60 of the median protein expression level. Comparisons of the proteome and the transcriptome, and analysis of protein complex databases and GO categories, suggest that we achieved deep coverage of the functional transcriptome and the proteome of a single cell type. PMID- 22068333 TI - Culturing adult canine sensory neurons to optimise neural repair. PMID- 22068332 TI - The quantitative proteome of a human cell line. AB - The generation of mathematical models of biological processes, the simulation of these processes under different conditions, and the comparison and integration of multiple data sets are explicit goals of systems biology that require the knowledge of the absolute quantity of the system's components. To date, systematic estimates of cellular protein concentrations have been exceptionally scarce. Here, we provide a quantitative description of the proteome of a commonly used human cell line in two functional states, interphase and mitosis. We show that these human cultured cells express at least -10 000 proteins and that the quantified proteins span a concentration range of seven orders of magnitude up to 20 000 000 copies per cell. We discuss how protein abundance is linked to function and evolution. PMID- 22068334 TI - Radiographic identification of the equine ventral conchal bulla. AB - Involvement of the ventral conchal sinus (VCS) is an important diagnostic and prognostic feature in cases of the equine sinus disease. The authors aimed to ascertain if the caudo-dorsal extension of the VCS, the ventral conchal bulla (VCB) is identifiable on plain radiographs of cadaver skulls without sinus disease. Bilateral frontonasal sinus flaps were made in 10 equine cadaver skulls. Plain lateral, lateral oblique and dorso-ventral radiographs were then obtained followed by the same views taken with stainless steel wire outlining the caudal border of the VCB. Plain radiographs were randomised and blindly evaluated by two observers who marked where they believed the VCB to be positioned. This was then correlated with the true position of the VCB using radiographs with wires in place. The ease of identification of the VCB was classified as 'easy' or 'difficult'. The VCB was correctly identified in 70 per cent of lateral radiographs, but only 45 per cent of lateral oblique radiographs and 17 per cent of dorso-ventral radiographs. If a clinician was confident that he or she could identify the VCB, they were usually correct. Conversely if the clinician judged VCB identification as 'difficult', they usually identified it incorrectly. In the authors' clinical experience, the VCB of horses with sinusitis involving this compartment is more radiologically evident than in clinically normal horses. Knowledge of the normal radiographic anatomy of this structure should aid clinicians in identifying horses with sinusitis affecting the VCS. PMID- 22068336 TI - A low cost point-of-care viscous sample preparation device for molecular diagnosis in the developing world; an example of microfluidic origami. AB - The lab-on-a-chip concept has led to several point-of-care (POC) diagnostic microfluidic platforms. However, few of these can process raw samples for molecular diagnosis and fewer yet are suited for use in a resource-limited setting without permanent electrical infrastructure. We present here a very low cost paper microfluidic device for POC extraction of bacterial DNA from raw viscous samples--a challenge for conventional microfluidic platforms. This is an example of "microfluidic origami" in that the system is activated by folding; demonstrated here is room temperature cell lysis and DNA extraction from pig mucin (simulating sputum) spiked with E. coli without the use of external power. The microfluidic origami device features dry reagent storage and rehydration of the lysis buffer. We demonstrate DNA extraction from samples with a bacterial load as low as 33 CFU ml(-1). Extraction times, starting from the raw sample, have been optimized to about 1.5 h without the use of external power, or to within 1 h using an oven or a heater block. The fabrication of this paper microfluidic device can be translated into high volume production in the developing world without the need for a semiconductor clean room or a microfabrication facility. The sample preparation can be performed with the addition of just the sample, water, ethanol and elute buffer to the device, thus reducing chemical hazards during transport and handling. PMID- 22068337 TI - Target organ damage in African American hypertension: role of APOL1. AB - Apolipoprotein L1 (APOL1) gene association studies and results of the African American Study of Kidney Disease and Hypertension are disproving the longstanding concept that mild to moderate essential hypertension contributes substantially to end-stage renal disease susceptibility in African Americans. APOL1 coding variants underlie a spectrum of kidney diseases, including that attributed to hypertension (labeled arteriolar or hypertensive nephrosclerosis), focal segmental glomerulosclerosis, and HIV-associated nephropathy. APOL1 nephropathy risk variants persist because of protection afforded from the parasite that causes African sleeping sickness. This breakthrough will lead to novel treatments for hypertensive African Americans with low-level proteinuria, for whom effective therapies are lacking. Furthermore, APOL1 nephropathy risk variants contribute to racially variable allograft survival rates after kidney transplantation and assist in detecting nondiabetic forms of nephropathy in African Americans with diabetes. Discovery of APOL1-associated nephropathy was a major success of the genetics revolution, demonstrating that secondary hypertension is typically present in nondiabetic African Americans with nephropathy. PMID- 22068335 TI - Common genetic variation in the 3'-BCL11B gene desert is associated with carotid femoral pulse wave velocity and excess cardiovascular disease risk: the AortaGen Consortium. AB - BACKGROUND: Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. METHODS AND RESULTS: We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3'-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, beta=-0.075+/-0.012 SD/allele, P=2.8*10(-10); replication beta= 0.086+/-0.020 SD/allele, P=1.4*10(-6)). Combined results for rs7152623 from 11 cohorts gave beta=-0.076+/-0.010 SD/allele, P=3.1*10(-15). The association persisted when adjusted for mean arterial pressure (beta=-0.060+/-0.009 SD/allele, P=1.0*10(-11)). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, beta=-0.081+/-0.014 SD/allele, P=2.3*10(-9)) and older (9 cohorts, n=12 026, beta=-0.061+/-0.014 SD/allele, P=9.4*10(-6)) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02-1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03-1.16, P=0.004). CONCLUSIONS: Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events. PMID- 22068339 TI - Differential effects of selenium and knock-down of glutathione peroxidases on TNFalpha and flagellin inflammatory responses in gut epithelial cells. AB - Selenium (Se) is essential for human health. Despite evidence that Se intake affects inflammatory responses, the mechanisms by which Se and the selenoproteins modulate inflammatory signalling, especially in the gut, are not yet defined. The aim of this work was to assess effects of altered Se supply and knock-down of individual selenoproteins on NF-kappaB activation in gut epithelial cells. Caco-2 cells were stably transfected with gene constructs expressing luciferase linked either to three upstream NF-kappaB response elements and a TATA box or only a TATA box. TNFalpha and flagellin activated NF-kappaB-dependent luciferase activity and increased IL-8 expression. Se depletion decreased expression of glutathione peroxidase1 (GPX1) and selenoproteins H and W and increased TNFalpha stimulated luciferase activity, endogenous IL-8 expression and reactive oxygen species (ROS) production. These effects were not mimicked by independent knock down of either GPX1, selenoprotein H or W; indeed, GPX1 knock-down lowered TNFalpha-induced NF-kappaB activation and did not affect ROS levels. GPX4 knock down decreased NF-kappaB activation by flagellin but not by TNFalpha. We hypothesise that Se depletion alters the pattern of expression of multiple selenoproteins that in turn increases ROS and modulates NF-kappaB activation in epithelial cells, but that the effect of GPX1 knock-down is ROS-independent. PMID- 22068338 TI - Disorders of blood pressure regulation-role of catecholamine biosynthesis, release, and metabolism. AB - Catecholamines (epinephrine and norepinephrine) are synthesised and produced by the adrenal medulla and postganglionic nerve fibres of the sympathetic nervous system. It is known that essential hypertension has a significant neurogenic component, with the rise in blood pressure mediated at least in part by overactivity of the sympathetic nervous system. Moreover, novel therapeutic strategies aimed at reducing sympathetic activity show promise in the treatment of hypertension. This article reviews recent advances within this rapidly changing field, particularly focusing on the role of genetic polymorphisms within key catecholamine biosynthetic enzymes, cofactors, and storage molecules. In addition, mechanisms linking the sympathetic nervous system and other adverse cardiovascular states (obesity, insulin resistance, dyslipidaemia) are discussed, along with speculation as to how recent scientific advances may lead to the emergence of novel antihypertensive treatments. PMID- 22068340 TI - Associations between functional polymorphisms in antioxidant defense genes and urinary oxidative stress biomarkers in healthy, premenopausal women. AB - Functional polymorphisms in endogenous antioxidant defense genes including manganese superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX-1) have been linked with risk of cancer at multiple sites. Although it is presumed that these germline variants impact disease risk by altering the host's ability to detoxify mutagenic reactive oxygen species, very few studies have directly examined this hypothesis. Concentrations of 8 isoprostane F2alpha (8-iso-PGF2alpha) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8 oxoxdG)-sensitive indicators of lipid peroxidation and DNA oxidation, respectively-were measured in 24-h urine samples obtained from 93 healthy, premenopausal women participating in a dietary intervention trial. In addition, DNA was extracted from blood for genotyping of MnSOD Val16Ala, CAT-262 C > T, and GPX1 Pro198Leu genotypes by Taqman assay. Although geometric mean concentrations of 8-iso-PGF2(alpha) and 8-oxoxdG varied across several study characteristics including race, education level, body mass index, and serum antioxidant levels, there was little evidence that these biomarkers differed across any of the examined genotypes. In summary, functional polymorphisms in endogenous antioxidant defense genes do not appear to be strongly associated with systemic oxidative stress levels in young, healthy women. PMID- 22068342 TI - The Neuroscience of Happiness and Pleasure. PMID- 22068346 TI - Improvement of in vitro-transcribed amber suppressor tRNAs toward higher suppression efficiency in wheat germ extract. AB - In vitro-transcribed, unmodified, and non-aminoacylated amber suppressor tRNAs that are recognized by natural aminoacyl-tRNA synthetase were improved toward higher suppression efficiency in batch-mode cell-free translation in wheat germ extract. The suppression efficiency of the suppressor obtained through four sequence optimization steps (anticodon alteration of natural tRNAs (the first generation); chimerization of the efficient suppressors in the first generation; investigation and optimization of the effective parts in the second generation; combination of the optimized parts in the third generation) and by the terminal tuning was approximately 60%, which was 2.4-fold higher than that of the best suppressor in the first generation. In addition, an eRF1 aptamer further increased the efficiency up to 85%. This highly efficient suppression system also functioned well in a dialysis-based large-scale protein synthesis. PMID- 22068350 TI - COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes. AB - Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-diHETE and 5,11-diHETE in isolated human leukocytes activated with lipopolysaccharide and calcium ionophore A23187. Transformation of arachidonic acid was initiated by 5-LOX providing 5S-HETE as a substrate for COX-2 forming 5S,15S-diHETE, 5S,15R-diHETE, and 5S,11R-diHETE as shown by LC/MS and chiral phase HPLC analyses. The levels of 5,15-diHETE were 0.45 +/- 0.2 ng/106 cells (mean +/- SEM, n = 6), reaching about half the level of LTB4 (1.3 +/- 0.5 ng/106 cells, n = 6). The COX-2 specific inhibitor NS-398 reduced the levels of 5,15-diHETE to below 0.02 ng/106 cells in four of six samples. Similar reduction was achieved by MK-886, an inhibitor of 5-LOX activating protein but the above differences were not statistically significant. Aspirin treatment of the activated cells allowed formation of 5,15-diHETE (0.1 +/ 0.05 ng/106 cells, n = 6) but, as expected, abolished formation of 5,11-diHETE. The mixture of activated cells also produced 5S,12S-diHETE with the unusual 6E,8Z,10E double bond configuration, implicating biosynthesis by 5-LOX and 12-LOX activity rather than by hydrolysis of the leukotriene A4-epoxide. Exogenous octadeuterated 5S-HETE and 15S-HETE were converted to 5,15-diHETE, implicating that multiple oxygenation pathways of arachidonic acid occur in activated leukocytes. The contribution of COX-2 to the biosynthesis of dihydroxylated derivatives of arachidonic acid provides evidence for functional coupling with 5 LOX in activated human leukocytes. PMID- 22068351 TI - Serum levels of TNF-alpha, IL-1beta, COMP, and CTX-II in patients with Kashin Beck disease in Sichuan, China. AB - The aim of the study was to detect differences in serum levels of interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), cartilage oligomeric matrix protein (COMP), type II collagen (CTX-II) between patients with Kashin Beck disease (KBD) or osteoarthritis (OA) and to assess the correlation between these differences with the clinical grade of KBD. A total of one hundred fifty adult serum samples were collected; these samples belonged to the KBD group (n = 64), the OA group in KBD-prevalent areas (n = 47) and a healthy control group in non-KBD area (n = 39). Serum levels of TNF-alpha, IL-1beta, COMP, and CTX-II were determined by a sandwich enzyme-linked immunosorbent assay, and the results were compared among the 3 groups (KBD/OA/normal) and between the different grades of KBD as well. The serum levels of IL-1beta, TNF-alpha, COMP, and CTX-II were significantly higher in the KBD and OA group than the healthy adult group (P < 0.001), and TNF-alpha and IL-1beta levels in the KBD group were similar to the OA group (for TNF-alpha, 14.38 +/- 7.42 pg/ml vs. 12.61 +/- 4.00 pg/ml, respectively, [P = 0.29]; for IL-1beta, 141.53 +/- 71.35 pg/ml vs. 135.61 +/- 68.60 pg/ml, respectively, [P = 0.63]). However, the COMP level was significantly lower and the CTX-II level was higher in the KBD group than in the OA group (for COMP, 7.03 +/- 3.11 ng/ml vs. 9.20 +/- 3.51 ng/ml, respectively, [P = 0.003]; for CTX-II, 2.23 +/- 0.79 ng/ml vs. 1.80 +/- 0.87 ng/ml, respectively, [P = 0.026]). Moreover, no significant correlations were found between clinical grade and serum levels of TNF-alpha, IL-1beta, COMP, and CTX-II for the 3 grades of KBD patients (P = 0.645, 0.481, 0.832, and 0.270, respectively). This study showed that serum levels of COMP in KBD patients decreased and CTX-II levels increased compared with the levels in OA patients, but TNF-alpha and IL-1beta levels in KBD and OA group were similar. In addition, increased serum levels of TNF-alpha, IL-1beta, COMP, and CTX-II were not associated with the KBD grade. PMID- 22068353 TI - RETRACTED ARTICLE: An evidence-based review of the most current treatment options and trends for carpal tunnel syndrome (CTS). PMID- 22068354 TI - Rapid infusion with rituximab: short term safety in systemic autoimmune diseases. AB - To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient (1.8%) had grade 2 events on both infusions and two patients (3.6%) had a grade 3 event on both infusions. RA patients more often had an infusion-related reaction (IRR) (9.2%) than the rest. The types of IRR were mostly of allergic or angio-oedematic nature. In practise, the rapid infusion was an easy to use regime and the second infusion is of time sparing significance to health professionals. No unexpected side effects were observed in relation to the accelerated regime. PMID- 22068352 TI - Antibodies to mutated citrullinated vimentin in patients with chronic hepatitis C virus genotype IV infection-related arthropathy. AB - One of the extra-hepatic manifestations of hepatitis C virus (HCV) infection is polyarthritis that mimics rheumatoid arthritis (RA). Anti-mutated citrullinated vimentin (MCV) was recently introduced in the diagnostic workup of RA, but its exact role in HCV infection and its related arthropathy is still unclear. The aim of the study is to determine the prevalence of anti-MCV antibodies in HCV infected patients with or without articular involvement, and to investigate whether anti-MCV antibodies have an additional role to anticyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) in differentiating patients with RA from patients with HCV-related arthropathy. Fifty-five HCV-infected patients (HCV RNA positive) and 30 RA patients (fulfilling the American College of Rheumatology classification criteria for RA and negative for HCV) were included. Anti-MCV antibodies, anti-CCP antibodies, RF and cryoglobulins were measured. Articular involvement in hepatitis C patients was evaluated. Articular involvement was detected in 30/55 (54.5%) of HCV-infected patients. The most frequent pattern was symmetric polyarthralgias and the most frequent joints to be involved were the wrists, metacarpophalangeal joints, shoulders and knees. In HCV arthropathy, anti-MCV was positive in 9/30 (30%), anti-CCP in 0% and RF in 22/30 (73.3%). Whereas, in chronic HCV without arthropathy, anti-MCV was positive in 8 patients (32%), anti-CCP in one patient (4%) and RF in 23/25 (92.0%). There was no significant difference between the two HCV groups as regards the frequencies of anti-MCV (P = 0.89), anti-CCP (P = 0.93) and RF (P = 0.15). In RA, anti-MCV was positive in 93.3% anti-CCP in 96.7% and RF in 86.7%. There was no significant difference in RF between RA and HCV arthropathy (P = 0.33). Meanwhile, there was a highly significant difference between both groups regarding anti-MCV and anti CCP (P < 0.0001 for each). The sensitivity of anti-MCV, anti-CCP and RF for RA was 93.3, 96.7 and 86.7%, respectively. Whereas their specificity was 69.1, 98.2 and 18.2%, respectively. In addition, the mean levels of anti-MCV and anti-CCP were significantly increased in RA than in all HCV patients (P = 0.038 and P < 0.0001, respectively). Meanwhile, there were no significant differences in mean levels of anti-MCV and anti-CCP between HCV patients with arthropathy and those without arthropathy (P = 0.11 and P = 0.73, respectively). Also, there were no differences in mean RF between both HCV groups. There was a significant positive correlation between anti-MCV and anti-CCP levels in patients with HCV-related arthropathy (r = 0.39, P = 0.032) and in those without arthropathy (r = 0.578, P = 0.002). Cryoglobulins were detected in 7/30 HCV-related arthropathy (23.3%) and were positively correlated with anti-MCV(r = 0.485, P = 0.007). Anti-CCP still attains the major role in differentiating RA from HCV arthropathy. Anti-MCV seems to play no additional role in this aspect. The role of mutation of vimentin in the pathogenesis of HCV arthropathy is not as clear as it is for RA and needs further investigation. PMID- 22068356 TI - Exercise for fibromyalgia: evidence for an integrated modulation of autonomic and nociception neural regulation. PMID- 22068355 TI - Angiogenic growth factors in rheumatoid arthritis. AB - We investigated whether the angiogenic profile, which is based on the local expression and systemic levels of angiogenic growth factors (VEGF, Ang-1, Ang-2, and the corresponding receptors), differs between rheumatoid arthritis (RA) and osteoarthritis (OA) patients. We determined the expression of VEGF, Ang-1, and Ang-2 together with its receptors (VEGFR-1/-2 and Tie2) in synovium tissue (ST) and muscular tissue (MT) from patients with RA and OA using quantitative PCR. Tissue samples were obtained from 15 RA and 19 OA patients during total knee arthroplasty. Control MT samples (n = 10) were obtained during spinal surgery. Results are correlated to VEGF and angiopoietin serum levels via ELISA measurements. The VEGF expressions in ST and serum levels were significantly higher in RA patients than in OA patients (P < 0.05). Furthermore, the VEGFR-1 and VEGFR-2 expression in ST from RA patients were significantly higher than in OA patients (P < 0.001 and P < 0.05). The relative concentration of angiopoietins (Ang-1/Ang-2 ratio) was significantly increased in RA (P < 0.01). Serum levels for Ang-2 showed no significant differences. Statistical analysis showed a significant higher level of Tie2 in RA patients (P < 0.001). Analysis of local levels of VEGF, VEGFR-1, VEGFR-2, Ang-1, Ang-2, and Tie2 in the muscular tissue showed no significant difference between RA and OA patients. These results underline the importance of pro-angiogenic growth factor levels for RA corroborating the assumption that VEGF and angiopoietins play an important role in the pathogenesis of RA. PMID- 22068357 TI - Health promotion in the workplace: assessing stress and lifestyle with an intranet tool. AB - BACKGROUND: Chronic noncommunicable conditions, particularly cardiovascular and metabolic diseases, are the major causes of death and morbidity in both industrialized and low- to middle-income countries. Recent epidemiological investigations suggest that management of lifestyle factors, such as stress and lack of physical activity, could have an important value in cardiometabolic conditions, while information technology tools could play a significant facilitatory role. OBJECTIVES: The objective of our study was to verify the feasibility of using a private website, directed to the workers of a major Italian company, to describe their health profile and lifestyle and work habits using an ad hoc self-administered questionnaire. METHODS: We administered anonymous multiple choice Web-based questionnaires to 945 participants (683 completed the task) as part of an ongoing health promotion program in a multinational company. Qualitative and quantitative data were synthesized with nonlinear principal component analysis to construct indicators (ie, variables) for stress, control, and lifestyle domains. Considering in addition absenteeism, the Calinski-Harabasz statistic and cluster analysis jointly differentiated seven clusters, which displayed different distributions of standardized classification variables. The final step consisted in assessing the relationship of the resulting seven subject typologies with personal data, illnesses, and metabolic syndrome status, carried out for the most part with descriptive methods. RESULTS: Statistical analyses singled out two not-overlapping domains of stress and control, as well as three not-overlapping domains of physical activity, smoking, and alcohol habits. The centroids of the seven clusters generated by the procedure were significantly (P < .001) different considering all possible 21 comparisons between couples of groups. Percentage distributions of variables describing personal information (gender, age group, work category, illness status, or metabolic syndrome) within participant typologies show some noteworthy findings: females, workers aged 35-44 years, junior white collar workers, and respondents reporting illness were more prevalent in the stress group than in the overall studied population; preclinical metabolic syndrome status was more prevalent in the group with higher alcohol consumption. Absentees reported more illness. CONCLUSIONS: The present Intranet-based study shows the potential of applying diverse statistical techniques to deal jointly with qualitative and quantitative self-reported data. The resulting formal description of subject typologies and their relationship with personal characteristics might provide a convenient tool for supporting health promotion in the work environment. PMID- 22068358 TI - Cross-site evaluation of a comprehensive pediatric asthma project: the Merck Childhood Asthma Network, Inc. (MCAN). AB - The Merck Childhood Asthma Network, Inc. (MCAN) initiative selected five sites that had high asthma burden and established asthma programs but were ready for greater program integration across schools, health care systems, and communities. MCAN supported a community-based approach that was tailored to the needs of each program site. As a result, each site was unique in its combination of interventions, but all sites served common goals of integration of care, incorporation of evidence-based programs, and improvement in knowledge, self management, health, and quality of life. This case study of the MCAN cross-site evaluation discusses the challenges associated with evaluating interventions involving multiple stakeholders that have been adjusted to fit the unique needs of specific communities. The evaluation triangulates data from site-specific monitoring and evaluation data; site documents, site visits, and cross-site meetings; qualitative assessments of families, organizational partners, and other stakeholders; and quantitative data from a common instrument on health indicators before and after the intervention. The evaluation employs the RE-AIM framework- reach, effectiveness, adoption, implementation, and maintenance--to assess the barriers and facilitators of translation from theory into practice. Our experience suggests trade-offs between rigor of evaluation and burden of assessment that have applicability for other community-based translational efforts. PMID- 22068359 TI - Outcomes from a cross-site evaluation of a comprehensive pediatric asthma initiative incorporating translation of evidence-based interventions. AB - This article reports on an evaluation of the Merck Childhood Asthma Network, Inc. (MCAN) initiative using pooled cross-site data on patient-reported outcomes pre- and postintervention to quantify the changes experienced by children in five program sites supported by the network. The results show a consistent pattern of improvement across all measured outcomes, including symptoms, hospital and emergency department use, school absences, and caregiver confidence. Children who started with uncontrolled asthma experienced larger improvements than children with controlled asthma at baseline. However, even considering the significant gains made by children with uncontrolled asthma at baseline, after 12 months, most of the outcomes for these children were significantly worse than the 12 month outcomes for children with controlled asthma at baseline. The evaluation of the MCAN initiative offers a model that can be used in cases where resources must be balanced between evaluation and delivering services to children. The design process and results from the common survey instrument provide information for future initiatives seeking to translate evidence-based interventions in a community-based setting. PMID- 22068360 TI - Community-based care coordination: practical applications for childhood asthma. AB - Care coordination programs have been used to address chronic illnesses, including childhood asthma, but primarily via practice-based models. An alternative approach employs community-based care coordinators who bridge gaps between families, health care providers, and support services. Merck Childhood Asthma Network, Inc. (MCAN) sites developed community-based care coordination approaches for childhood asthma. Using a community-based care coordination logic model, programs at each site are described along with program operational statistics. Four sites used three to four community health workers (CHWs) to provide care coordination, whereas one site used five school-based asthma nurses. This school based site had the highest caseload (82.5 per year), but program duration was 3 months with 4 calls or visits. Other sites averaged fewer cases (35 to 61 per CHW per year), but families received more (7 to 17) calls or visits over a year. Retention was 43% to 93% at 6 months and 24% to 75% at 12 months. Pre-post cross site data document changes in asthma management behaviors and outcomes. After program participation, 93% to 100% of caregivers had confidence in controlling their child's asthma, 85% to 92% had taken steps to reduce triggers, 69% to 100% had obtained an asthma action plan, and 46% to 100% of those with moderate to severe asthma reported appropriate use of controller medication. Emergency department visits for asthma decreased by 36% to 63%, and asthma-related hospitalizations declined by 26% to 78%. More than three fourths had fewer school absences. In conclusion, MCAN community-based care coordination programs improved management behaviors and decreased morbidity across all sites. PMID- 22068361 TI - Translating evidence-based interventions into practice: the Merck Childhood Asthma Network, Inc. (MCAN) initiative. PMID- 22068362 TI - Balancing "fidelity" and community context in the adaptation of asthma evidence based interventions in the "real world". AB - The Merck Childhood Asthma Network (MCAN) initiative selected five sites (New York City, Puerto Rico, Chicago, Los Angeles, and Philadelphia) to engage in translational research to adapt evidence-based interventions (EBIs) to improve childhood asthma outcomes. The authors summarize the sites' experience by describing criteria defining the fidelity of translation, community contextual factors serving as barriers or enablers to fidelity, types of adaptation conducted, and strategies used to balance contextual factors and fidelity in developing a "best fit" for EBIs in the community. A conceptual model captures important structural and process-related factors and helps frame lessons learned. Site implementers and intervention developers reached consensus on qualitative rankings of the levels of fidelity of implementation for each of the EBI core components: low fidelity, adaptation (major vs. minor), or high fidelity. MCAN sites were successful in adapting core EBI components based on their understanding of structural and other contextual barriers and enhancers in their communities. Although the sites varied regarding both the EBI components they implemented and their respective levels of fidelity, all sites observed improvement in asthma outcomes. Our collective experiences of adapting and implementing asthma EBIs highlight many of the factors affecting translation of evidenced-based approaches to chronic disease management in real community settings. PMID- 22068363 TI - The role of partnerships in addressing childhood asthma: the experiences of the Merck Childhood Asthma Network, Inc. (MCAN) initiative. AB - Partnerships have taken on added importance in recent years because of their critical role in addressing complex public health problems and translating evidence-based practices to real-world settings. The Merck Childhood Asthma Network, Inc. initiative recognized the importance of partnerships in achieving the program's goals. In this article, case studies of the five Merck Childhood Asthma Network program sites describe the role of partnerships in the development and evolution of the program and its interventions. Three key factors contributed to the success of the partnerships: having common organizational goals, considering context in the selection and engagement of partners, and ensuring that each partnership benefited from the alliance. Over the 4-year program period, all five partnerships evolved, matured, and had an established goal to maintain collaboration. PMID- 22068364 TI - Desired attributes and skills of program managers in translation of evidence based interventions. AB - Successful chronic disease project management, especially of multiyear initiatives using evidence-based interventions (EBIs), is of great importance to funders, health care decision makers, and researchers, particularly in light of limited funding. However, a gap in knowledge may exist regarding which attributes and skills are most desirable in a program manager to help him or her ensure successful implementation of EBIs. Although some literature examines the dynamics contributing to the success of community coalitions, public health leadership, and community health education, there is minimal literature exploring the significance of a program manager's role in the conceptualization, implementation, and sustainability of initiatives to improve patient and community health. The authors present their experiences as participants in a large-scale asthma initiative implemented in priority communities, as well as results of a survey distributed among all personnel of the program sites. The survey aimed to assess the key skills and attributes, in addition to contextual factors, that contribute to the strength of a program manager overseeing EBIs in asthma initiatives. The results suggest that certain attributes and skills are desirable in recruiting and hiring of a program manager, especially when augmented by ongoing skill-building training, and can help ensure program and research success. PMID- 22068365 TI - Challenges and lessons learned from the translation of evidence-based childhood asthma interventions: a commentary on the MCAN initiative. AB - The Merck Childhood Asthma Network (MCAN) used evidence-based interventions (EBIs) for children with asthma to design community-based programs in a wide variety of settings--with varying resource constraints and priorities--that were often determined by the program context. Although challenges were faced, lessons learned strongly suggest that adapting and implementing EBIs is feasible in a variety of settings using a multisite approach. Lessons learned during the MCAN initiative presented unique opportunities to refine best practices that proved to be important to translation of EBIs in community-based settings. The adopted best practices were based on experiential learning during different phases of the project cycle, including monitoring and evaluation, translational research, and implementing policies in local program environments. Throughout this discussion it is important to note the importance of program context in determining the effectiveness of the interventions, opportunities to scale them, their affordability, and the ability to sustain them. Lessons learned from this effort will be important not only to advance science-based approaches to manage childhood asthma but also to assist in closing the gap between intervention development (discovery) and program dissemination and implementation (delivery). PMID- 22068366 TI - Translating evidence-based interventions into practice: the design and development of the Merck Childhood Asthma Network, Inc. (MCAN). AB - Pediatric asthma is a multifactorial disease, requiring complex, interrelated interventions addressing children, families, schools, and communities. The Merck Childhood Asthma Network, Inc. (MCAN) is a nonprofit organization that provides support to translate evidence-based interventions from research to practice. MCAN developed the rationale and vision for the program through a phased approach, including an extensive literature review, stakeholder engagement, and evaluation of funding gaps. The analysis pointed to the need to identify pediatric asthma interventions implemented in urban U.S. settings that have demonstrated efficacy and materials for replication and to translate the interventions into wider practice. In addition to this overall MCAN objective, specific goals included service and system integration through linkages among health care providers, schools, community-based organizations, patients, parents, and other caregivers. MCAN selected sites based on demonstrated ability to implement effective interventions and to address multiple contexts of pediatric asthma prevention and management. Selected MCAN program sites were mature institutions or organizations with significant infrastructure, existing funding, and the ability to provide services without requiring a lengthy planning period. Program sites were located in communities with high asthma morbidity and intended to integrate new elements into existing programs to create comprehensive care approaches. PMID- 22068367 TI - Successful treatment of toxic epidermal necrolysis/Stevens-Johnson syndrome overlap with human granulocyte colony stimulating factor: a case report. PMID- 22068368 TI - Residential treatment for homeless female veterans with psychiatric and substance use disorders: effect on 1-year clinical outcomes. AB - Limited evidence shows that time-limited residential treatment (RT) is beneficial for homeless people with serious mental illness. The Department of Veterans Affairs has established 11 specialty programs for homeless female veterans. We present data comparing 1-year clinical outcomes in a group of veterans who did and did not receive at least 30 days of RT. Clients of the Homeless Women Veterans Programs were invited to participate in a follow-up study. They were interviewed every 3 months for 1 year. Those who received at least 30 days of RT in the 3 months after program entry (RT group) were compared with other program participants (no or <30 days RT [NRT] group) on measures of community functioning, psychiatric symptoms, and drug and alcohol use during the follow-up. The RT group had better outcomes on employment, social support, housing status, and psychiatric symptoms. They also had significantly increased use of drugs and alcohol compared with the NRT group. Data suggest that RT may have a beneficial effect on mental health outcomes in homeless women. This study, in conjunction with others, suggests that provision of stable housing may be an important element of recovery for homeless women with psychiatric problems, excluding substance use. PMID- 22068369 TI - Physical activity in postdeployment Operation Iraqi Freedom/Operation Enduring Freedom veterans using Department of Veterans Affairs services. AB - Veteran activity levels may decrease between Active Duty and postdeployment. We examined attitudes and changes in self-reported activities between the two in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans using Department of Veterans Affairs (VA) services. We conducted an online cross sectional survey (June-August 2008) of postdeployment OIF/OEF veterans registered with the VA Ann Arbor Healthcare System, Ann Arbor, Michigan. Descriptive statistics summarized demographic data and attitudes, while regression analyses compared physical activities during Active Duty with physical activities postdeployment. Participants (n = 319, 15.6% response rate) reported that they believe staying physically fit is important, they worry about gaining weight, and they believe exercise will keep them healthy (77%, 72%, and 90% agree or strongly agree, respectively). Running (30.0%), Exercise with Gym Equipment (21.5%), Occupational Activities (14.9%), and Walking (13.0%) were the most frequently reported Active Duty physical activities. The most frequently reported postdeployment physical activities included Walking (21.1%), Running (18.5%), and Exercise with Gym Equipment (17.9%). Health problems (39%) and chronic pain (52%) were common barriers to physical activity. Postdeployment OIF/OEF veterans using the VA believe physical activity is beneficial, yet many report health problems and/or chronic pain that makes exercise difficult. Physical activity promotes health, and strategies are needed to facilitate physical activity in this population. PMID- 22068370 TI - Prevalence and characteristics of driving difficulties in Operation Iraqi Freedom/Operation Enduring Freedom combat returnees. AB - We studied the prevalence and characteristics of self-reported driving difficulties and examined their association with traumatic brain injury (TBI) and/or posttraumatic stress disorder (PTSD) in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans who were seen at a Department of Veterans Affairs outpatient polytrauma clinic. In this study, we used a brief driving questionnaire and chart reviews to assess the prevalence and characteristics of driving difficulties in the following four groups of patients: TBI only, PTSD only, TBI + PTSD, and Neither (neither TBI nor PTSD). Compared with before deployment, 93% of OIF/OEF veterans seen in the polytrauma clinic reported more difficulties with driving in at least one domain, with the most common areas of difficulty being (1) problems with anger or impatience (82%), (2) general driving difficulties (65%), and (3) experiences with near misses (57%). Patients with PTSD (with or without TBI) reported the most significant driving impairments, whereas respondents with a history of only TBI endorsed driving difficulties similar to veterans without either diagnosis. Qualitative analysis of veterans' comments also revealed similar patterns. Self-reported driving problems were common among OIF/OEF returnees. Respondents who had a diagnosis of PTSD (with or without TBI) reported the most severe driving difficulties since returning from deployment. The association between PTSD and driving problems warrants further investigation. PMID- 22068371 TI - Retrospective case series of clinical outcomes associated with chiropractic management for veterans with low back pain. AB - Musculoskeletal complaints, most notably low back pain (LBP), are prevalent among veterans. Despite a focus on LBP management by chiropractors within the Veterans Health Administration, limited published accounts detail clinical outcomes with chiropractic management of LBP among veterans. This was a retrospective case series of 171 veterans with a chief complaint of LBP who were managed with chiropractic care. Descriptive statistics and paired t-tests were used, with the Numeric Rating Scale (NRS) and the Back Bournemouth Questionnaire (BBQ) serving as the outcome measures. A minimum clinically important difference (MCID) was set as 30% improvement from baseline for both measures. The mean number of treatments was 8.7. For the NRS, the mean raw score improvement was 2.2 points, representing 37.4% change from baseline; 103 (60.2%) patients met or exceeded the MCID. For the BBQ, the mean raw score improvement was 13.6 points, representing 34.6% change from baseline; 92 patients (53.8%) met or exceeded the MCID. For this sample of veterans with LBP, the mean percentages of clinical improvement were statistically significant and clinically meaningful for both the NRS and BBQ. PMID- 22068372 TI - An objective method for selecting command sources for myoelectrically triggered lower-limb neuroprostheses. AB - Functional electrical stimulation (FES) facilitates ambulatory function after paralysis of persons with spinal cord injury (SCI) by exciting the peripheral motor nerves to activate the muscles of the lower limbs. This study identified a process for selecting command sources for triggering FES with the surface electromyogram (EMG) from muscles partially paralyzed by incomplete SCI, given its high degree of intersubject variability. We found Discriminability Index (DI) to be a good metric to evaluate the potential of controlling FES-assisted ambulation in four nondisabled volunteers and two participants with incomplete paralysis. The left erector spinae (ES) (mean DI = 0.87) for triggering the left step and the right ES (mean DI = 0.83) for triggering the right step were the best command sources for participant 1. The left ES (mean DI = 0.93) for triggering the left step and the right medial gastrocnemius (mean DI = 0.88) for triggering the right step were the best command sources for participant 2. Our results showed that command sources can be selected objectively from surface EMG before a fully implantable EMG-triggered FES system for walking is implemented. PMID- 22068373 TI - Residual limb volume change: systematic review of measurement and management. AB - Management of residual limb volume affects decisions regarding timing of fit of the first prosthesis, when a new prosthetic socket is needed, design of a prosthetic socket, and prescription of accommodation strategies for daily volume fluctuations. This systematic review assesses what is known about measurement and management of residual limb volume change in persons with lower-limb amputation. Publications that met inclusion criteria were grouped into three categories: group I: descriptions of residual limb volume measurement techniques; group II: studies investigating the effect of residual limb volume change on clinical care in people with lower-limb amputation; and group III: studies of residual limb volume management techniques or descriptions of techniques for accommodating or controlling residual limb volume. We found that many techniques for the measurement of residual limb volume have been described but clinical use is limited largely because current techniques lack adequate resolution and in-socket measurement capability. Overall, limited evidence exists regarding the management of residual limb volume, and the evidence available focuses primarily on adults with transtibial amputation in the early postoperative phase. While we can draw some insights from the available research about residual limb volume measurement and management, further research is required. PMID- 22068374 TI - Tensile strength and impact resistance properties of materials used in prosthetic check sockets, copolymer sockets, and definitive laminated sockets. AB - Prosthetic sockets serve as the interface between people with amputations and their prostheses. Although most materials used to make prosthetic sockets have been used for many years, knowledge of these materials' properties is limited, especially after they are subjected to fabrication processes. This study evaluated tensile and impact properties of the current state-of-the-art materials used to fabricate prosthetic check sockets, copolymer sockets, and definitive laminated sockets. Thermolyn Rigid and Orfitrans Stiff check socket materials produced significantly lower tensile strength and impact resistance than polyethylene terephthalate glycol (PETG). Copolymer socket materials exhibited greater resistance to impact forces than the check socket materials but lower tensile strengths than PETG. The heated molding processes, for the check socket and copolymer materials, reduced both tensile strength and elongation at break. Definitive laminated sockets were sorted according to fabrication techniques. Nyglass material had significantly higher elongation, indicating a more ductile material than carbon-based laminations. Carbon sockets with pigmented resin had higher tensile strength and modulus at break than nonpigmented carbon sockets. Elongation at yield and elongation at break were similar for both types of carbon based laminations. The material properties determined in this study provide a foundation for understanding and improving the quality of prosthetic sockets using current fabrication materials and a basis for evaluating future technologies. PMID- 22068375 TI - Bilateral upper-limb rehabilitation after stroke using a movement-based game controller. AB - This study aimed to determine the effectiveness of a bilateral, self-supported, upper-limb rehabilitation intervention using a movement-based game controller for people with chronic stroke. Fourteen participants received a control treatment, followed by a washout period, and then the intervention. The intervention comprised playing computer games with the CyWee Z (CyWee Group Ltd; Taipei, Taiwan), a movement-based game controller similar to the Nintendo Wii remote. The CyWee Z was incorporated into a handlebar, making bilateral exercises possible by allowing the unaffected side to support and assist the affected side. The intervention lasted for 8 to 10 sessions of 45 to 60 minutes over a period of 2.5 weeks. The Fugl-Meyer Assessment upper-limb section (FMA-UL) was used as the primary outcome. The Wolf Motor Function Test and the Disabilities of Arm, Shoulder, and Hand outcome measure were used as secondary outcomes. Postintervention, motor performance as measured by the FMA-UL was significantly improved compared with all preintervention assessments (p < 0.001), whereas no changes were found on both secondary outcomes. It can be concluded from this pilot study that upper-limb motor performance of adults with chronic stroke improves with repetitive, game-assisted, self-supported bilateral exercises. PMID- 22068376 TI - Development of custom measurement system for biomechanical evaluation of independent wheelchair transfers. AB - This study describes a new custom measurement system designed to investigate the biomechanics of sitting-pivot wheelchair transfers and assesses the reliability of selected biomechanical variables. Variables assessed include horizontal and vertical reaction forces underneath both hands and three-dimensional trunk, shoulder, and elbow range of motion. We examined the reliability of these measures between 5 consecutive transfer trials for 5 subjects with spinal cord injury and 12 nondisabled subjects while they performed a self-selected sitting pivot transfer from a wheelchair to a level bench. A majority of the biomechanical variables demonstrated moderate to excellent reliability (r > 0.6). The transfer measurement system recorded reliable and valid biomechanical data for future studies of sitting-pivot wheelchair transfers.We recommend a minimum of five transfer trials to obtain a reliable measure of transfer technique for future studies. PMID- 22068377 TI - Kinematic analysis of symmetric axial trunk rotation on dominant hip. AB - Axial rotation of the trunk has been reported as a significant risk of low back dysfunction. However, a lack of biomechanical investigation exists that explains how twisting is accomplished with simultaneous asymmetric handling between the hip joints and lumbar spine. We used a three-dimensional motion analysis to measure movements of the bilateral hips and lumbar spine. Forty-four persons participated in the study, and the results indicated that spinal range of motion (ROM) was significantly different based on dominance (F = 198.83, p = 0.001), region x dominance (F = 14.21, p = 0.001), and dominance x dimension (F = 141.08, p = 0.001). We also found a three-way interaction between region x dominance x dimension (F = 26.30, p = 0.001). These results indicated that the motion of the transverse and sagittal planes significantly increased when the participants attempted to rotate their hips, especially on the nondominant side. Decreased axial trunk ROM on the side of dominance might stiffen passive structures of the hip joints. The functions of the hip joints and lumbar spine might be altered three dimensionally based on the side of dominance. PMID- 22068378 TI - Smart rehabilitation for the 21st century: the Tampa Smart Home for veterans with traumatic brain injury. PMID- 22068379 TI - Multiply twinned Pt-Pd nanoicosahedrons as highly active electrocatalysts for methanol oxidation. AB - Bimetallic Pt-Pd nanoicosahedrons (NIs) with multiple {111} twins were obtained through a facile one-pot hydrothermal synthesis in a high shape selectivity of 82%. The {111}-enclosed NIs exhibited superior electrocatalytic activities to {111}-enclosed Pt-Pd nanotetrahedrons as well as commercial Pt catalysts (Pt black and Pt/C) for methanol oxidation. PMID- 22068383 TI - Examining the robustness of first-principles calculations for metal hydride reaction thermodynamics by detection of metastable reaction pathways. AB - First principles calculations have played a useful role in screening mixtures of complex metal hydrides to find systems suitable for H(2) storage applications. Standard methods for this task efficiently identify the lowest energy reaction mechanisms among all possible reactions involving collections of materials for which DFT calculations have been performed. The resulting mechanism can potentially differ from physical reality due to inaccuracies in the DFT functionals used, or due to other approximations made in estimating reaction free energies. We introduce an efficient method to probe the robustness of DFT-based predictions that relies on identifying reactions that are metastable relative to the lowest energy reaction path predicted with DFT. An important conclusion of our calculations is that in many examples DFT cannot unambiguously predict a single reaction mechanism for a well defined metal hydride mixture because two or more mechanisms have reaction energies that differ by a small amount. Our approach is illustrated by analyzing a series of single step reactions identified in our recent work that examined reactions with a large database of solids [Kim et al., Phys. Chem. Chem. Phys. 2011, 13, 7218]. PMID- 22068382 TI - Case report: a p.C618S RET proto-oncogene germline mutation in a large Chinese pedigree with familial medullary thyroid carcinoma. AB - We report a Chinese pedigree with familial medullary thyroid carcinoma. Direct sequencing of the entire coding sequences of Rearranged during Transfection (RET) identified a recurrent c.T1852A (p.C618S) mutation in 13 of 23 members. The polymorphisms c.A135G (p.A45A), c.A1296G (p.A432A), c.T2307G (p.L769L) and IVS19 + 15T > C were also found in 13 carriers, and c.G2073A (p.G691S) was found in 1 carrier. Of the 13 carriers, seven (mean age: 42.6 years, range: 27-64) presented MTC as the isolated clinical phenotype, with elevated basal serum calcitonin (average: 1077.9 ng/L, range: 504-2,652) and a mean diameter of thyroid nodules of 2.97 cm (range: 1.6-4.3); they underwent a total thyroidectomy with modified bilateral/unilateral neck dissection and/or level VI lymph node dissection. The other 6 carriers did not accept surgery (4 rejected, 2 awaited). These were 2 older patients (63 and 32 years) with elevated calcitonin (1359 and 41.4 ng/L) and multi-centric hypoechoic nodules (1.5 and 0.6 cm) with calcifications in both/left thyroid lobes; and Doppler ultrasound showed normal bilateral thyroids in 4 younger carriers (median age: 8.3 years, range: 4-12) but with increased calcitonin (average: 9.7 ng/L, range: 7.87-12.2) in 3 of them. The phenotype here is consistent with the clinical symptoms reported worldwide. We recommend that screening of hotspot regions of RET should be preferentially carried out, while whole-exon sequencing should be performed when clinical signs fail to reveal hotspot mutations or different phenotype discrepancies. Moreover, we strongly suggest prophylactic thyroidectomy should be performed before age 5 in carriers with p.C618S to prevent the occurrence and metastasis of MTC. PMID- 22068384 TI - Predictors and outcomes of feeling of insufficient consultation time in cancer care in Korea: results of a nationwide multicenter survey. AB - BACKGROUND: Shared decision making and an integrative approach is expected to result in better outcomes, but might require more time. While ensuring that sufficient consultation time is essential to quality cancer care, it is not clear whether cancer patients feel that the amount of consultation time with their oncologists is sufficient. METHODS: Data were collected from 2,556 cancer patients on their perceived and preferred consultation time, and included potential predictors, such as socio-demographics, clinical, behavioral, and quality-of-life factors, as well as potential outcomes, including unmet patient needs, trust in doctor, and satisfaction. The feeling of insufficient consultation time was defined as the perception that consultation time is less than the preferred consultation time; multivariate analyses were used for identification of predictors and comparison of outcomes. RESULTS: Overall, 37.1% felt that consultation time was less than preferred. Younger age, female sex, higher education level, having national health insurance, having been diagnosed with less common cancers, and having anxiety/depression were significantly associated with feelings of insufficient consultation time. Subjects with a feeling of insufficient consultation time reported higher current needs for information, physical symptoms, and psychological problems. They also reported less trust in their physician, lower overall satisfaction, and lower intention to continue treatment at the current cancer center. CONCLUSION: This study illustrated that high-quality cancer care, characterized by shared decision making and an integrative approach, seems to be related to sufficient consultation time that meets the individual's subjective needs, and measures should be taken to ensure sufficient consultation time. PMID- 22068385 TI - Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes. AB - To determine whether undercarboxylated osteocalcin (UC-OC) or gamma carboxyglutamic-carboxylated-type osteocalcin (GLA-OC) concentrations deviate from normal in type 1 diabetes (T1D), serum levels were compared between 115 subjects with T1D and 55 age-matched healthy controls. UC-OC and GLA-OC concentrations were similar between groups; however, in T1D, UC-OC correlated positively with markers of insulin exposure, either endogenously produced or exogenously administered. INTRODUCTION: A study was conducted to determine whether dysregulation of circulating concentrations of UC-OC or GLA-OC occurs in patients with type 1 diabetes, a condition of insulin deficiency without insulin resistance. METHODS: We measured serum concentrations of UC-OC and GLA-OC in 115 subjects with T1D, ages 14-40 years, and in 55 age-matched healthy control subjects. Relationships between UC-OC and GLA-OC concentrations and patient characteristics (gender and age), indices of glycemic control (hemoglobin A1c (HbA1c), fasting plasma glucose, C-peptide concentration, 3-day average glucose measured by a continuous glucose sensor, total daily insulin dose) and circulating indices of skeletal homeostasis (total calcium, 25-OH vitamin D, parathyroid hormone, insulin-like growth factor 1 (IGF-1), type 1 collagen degradation fragments (CTX), adiponectin, leptin) were examined. Between group differences in the concentrations of UC-OC and GLA-OC were the main outcome measures. RESULTS: Although adiponectin levels were higher in the T1D group, between-group comparisons did not reveal statistically significant differences in concentration of UC-OC, GLA-OC, CTX or leptin between the T1D and control populations. Instead, by multivariate regression modeling, UC-OC was correlated with younger age (p < 0.001), higher CTX (p < 0.001), lower HbA1c (p = 0.013), and higher IGF-1 (p = 0.086). Moreover, within the T1D subgroup, UC-OC was positively correlated with C-peptide/glucose ratio (reflecting endogenous insulin secretion), with IGF-1 (reflecting intra-portal insulin sufficiency), and with total daily insulin dose. CONCLUSIONS: In T1D, UC-OC appears to correlate positively with markers of insulin exposure, either endogenously produced or exogenously administered. PMID- 22068386 TI - Excess mortality after hip fracture among elderly women in Norway. The HUNT study. AB - We wanted to study mortality after hip fractures among elderly women in Norway. We found that excess mortality was highest short time after hip fracture, but persisted for several years after the fracture. The excess mortality was not explained by pre-fracture medical conditions. INTRODUCTION: The purpose of the present study was to investigate short and long term mortality after hip fracture, and to evaluate how comorbidity, bone mineral density, and lifestyle factors affect the survival after hip fractures. METHODS: The study cohort emerges from a population-based health survey in the county of Nord-Trondelag, Norway. Women aged 65 or more at participation at the health survey who sustained a hip fracture after attending the health survey are cases in this study (n = 781). A comparison cohort was constructed based on participants at HUNT 2 with no history of hip fractures (n = 3, 142). Kaplan-Meier survival curves were used to evaluate crude survival, and Cox regression analyses were used to study age adjusted hazard ratios for mortality and for multivariable analyses involving relevant covariates. RESULTS: Mean length of follow-up after fracture was 2.8 years. Within the first 3 months of follow-up, 78 (10.0%) of the hip fracture patients died, compared to only 39 (1.7%) in the control group. HR for mortality 3 months after hip fracture was 6.5 (95% CI 4.2-9.6). For the entire follow-up period women who sustained a hip fracture had an HR for mortality of 1.9 (95% CI 1.6-2.3), compared with women without a hip fracture. CONCLUSIONS: We found that elderly women who sustained a hip fracture had increased mortality risk. The excess mortality was highest short time after the fracture, but persisted for several years after the fracture, and was not explained by pre-fracture medical conditions. PMID- 22068388 TI - Airlift column photobioreactors for Porphyridium sp. culturing: Part II. verification of dynamic growth rate model for reactor performance evaluation. AB - Dynamic growth rate model has been developed to quantify the impact of hydrodynamics on the growth of photosynthetic microorganisms and to predict the photobioreactor performance. Rigorous verification of such reactor models, however, is rare in the literature. In this part of work, verification of a dynamic growth rate model developed in Luo and Al-Dahhan (2004) [Biotech Bioeng 85(4): 382-393] was attempted using the experimental results reported in Part I of this work and results from literature. The irradiance distribution inside the studied reactor was also measured at different optical densities and successfully correlated by the Lambert-Beer Law. When reliable hydrodynamic data were used, the dynamic growth rate model successfully predicted the algae's growth rate obtained in the experiments in both low and high irradiance regime indicating the robustness of this model. The simulation results also indicate the hydrodynamics is significantly different between the real algae culturing system and an air water system that signifies the importance in using reliable data input for the growth rate model. PMID- 22068389 TI - Biosynthesis of polyhydroxyalkanaotes by a novel facultatively anaerobic Vibrio sp. under marine conditions. AB - Marine bacteria have recently attracted attention as potentially useful candidates for the production of practical materials from marine ecosystems, including the oceanic carbon dioxide cycle. The advantages of using marine bacteria for the biosynthesis of poly(hydroxyalkanoate) (PHA), one of the eco friendly bioplastics, include avoiding contamination with bacteria that lack salt water resistance, ability to use filtered seawater as a culture medium, and the potential for extracellular production of PHA, all of which would contribute to large-scale industrial production of PHA. A novel marine bacterium, Vibrio sp. strain KN01, was isolated and characterized in PHA productivity using various carbon sources under aerobic and aerobic-anaerobic marine conditions. The PHA contents of all the samples under the aerobic-anaerobic condition, especially when using soybean oil as the sole carbon source, were enhanced by limiting the amount of dissolved oxygen. The PHA accumulated using soybean oil as a sole carbon source under the aerobic-anaerobic condition contained 14% 3 hydroxypropionate (3HP) and 3% 5-hydroxyvalerate (5HV) units in addition to (R)-3 hydroxybutyrate (3HB) units and had a molecular weight of 42 * 103 g/mol. The present result indicates that the activity of the beta-oxidation pathway under the aerobic-anaerobic condition is reduced due to a reduction in the amount of dissolved oxygen. These findings have potential for use in controlling the biosynthesis of long main-chain PHA by regulating the activity of the beta oxidation pathway, which also could be regulated by varying the dissolved oxygen concentration. PMID- 22068390 TI - Heat shock protein gene family of the Porphyra seriata and enhancement of heat stress tolerance by PsHSP70 in Chlamydomonas. AB - Heat shock proteins and molecular chaperones are key components contributing to survival in the abiotic stress response. Porphyra seriata grows on intertidal rocks exposed to dynamic environmental changes associated with the turning tides, including desiccation and heat stress. Analysis of the ESTs of P. seriata allows us to identify the nine HSP cDNAs, which are predicted to be PsHSP90, three PsHSP70, PsHSP40 and PsHSP20, and three 5'-truncated HSP cDNAs. RT-PCR results show that most of the PsHSP transcripts were detected under normal cell growth conditions as well as heat stress, with the exception of two cDNAs. In particular, PsHSP70b and PsHSP20 transcripts were upregulated by heat stress. When the putative mitochondrial PsHSP70b was introduced and overexpressed in Chlamydomonas, transformed Chlamydomonas evidenced higher rates of survival and growth than those of the wild type under heat stress conditions. Constitutive overexpression of the PsHSP70b gene increases the transcription of the HSF1 as well as the CrHSP20 and CrHSP70 gene. These results indicate that PsHSP70b is involved in tolerance to heat stress and the effects on transcription of the CrHSP20 and CrHSP70 genes. PMID- 22068391 TI - Young research investigators honored at the 2011 Gordon research conference on photosynthesis: ambiance and a perspective. PMID- 22068392 TI - Buoying health by building communities. PMID- 22068393 TI - The UN weighs solutions to the plague of noncommunicable disease. PMID- 22068394 TI - How the health and community development sectors are combining forces to improve health and well-being. AB - The root causes of poor health experienced by many who live in low-income neighborhoods-such as the lack of access to health care, limited food choices, and exposure to environmental hazards-are well documented, but often go beyond the scope of the health care delivery system. But that is beginning to change. The health sector has begun to collaborate with the community development sector, which for decades has been working in low-income neighborhoods. Encouraging local and national examples of these new partnerships abound. They include an effort in Seattle, Washington, to reduce exposure to allergens and irritants among low income asthmatic children, and a $500 million federal program to finance the operation of grocery stores in what have previously been urban "food deserts." To nurture such efforts, the Robert Wood Johnson Foundation, the Federal Reserve System, and others have sponsored a series of "healthy community" forums in US cities. In this article we explore the growing partnerships between the health and community development sectors as well as the challenges they face, and we offer policy recommendations that might help them succeed. PMID- 22068395 TI - Community development efforts offer a major opportunity to advance Americans' health. AB - Large differences in the opportunities and resources that Americans have to be healthy have led to sizable variations in health by geography, race and ethnicity, income level, and education. By enhancing the opportunities for good health in the places where we live, learn, work, play, and worship, community development initiatives can be important drivers of improved health. As articles in this month's issue of Health Affairs attest, community development and public health are two forces that often have the same goals. Because there has been little research to date documenting which aspects of community development could have the greatest impact on health, it will be increasingly necessary to rigorously evaluate the impact of various interventions to guide policy makers in identifying the most important measures to take in an environment of constrained financial resources. PMID- 22068396 TI - Partnerships among community development, public health, and health care could improve the well-being of low-income people. AB - Safe, vibrant neighborhoods are vital to health. The community development "industry"-a network of nonprofit service providers, real estate developers, financial institutions, foundations, and government-draws on public subsidies and other financing to transform impoverished neighborhoods into better-functioning communities. Although such activity positively affects the "upstream" causes of poor health, the community development industry rarely collaborates with the health sector or even considers health effects in its work. Examples of initiatives-such as the creation of affordable housing that avoids nursing home placement-suggest a strong potential for cross-sector collaborations to reduce health disparities and slow the growth of health care spending, while at the same time improving economic and social well-being in America's most disadvantaged communities. We propose a four-point plan to help ensure that these collaborations achieve positive outcomes and sustainable progress for residents and investors alike. PMID- 22068397 TI - Despite obstacles, considerable potential exists for more robust federal policy on community development and health. AB - The implementation of the Affordable Care Act of 2010 and the Obama administration's urban policy create an opportunity to link community development with health in new and powerful ways. The administration's policy emphasizes improved access to and quality of care through coordinated local and regional approaches, expansion of access to healthy food, and the support of environmental health-including clean air, water, and soil-and healthy homes. New federal programs, such as the Affordable Care Act's Community Transformation Grants, seek to prevent death and disability through policy, environmental, programmatic, and infrastructure changes. But fragmented congressional jurisdiction and budget "scoring" rules pose challenges to needed reform. We argue that government agencies need to adopt so-called systems of innovation, or organizational practices and support mechanisms that seek continuously to test new models, refine promising ones, bring to scale those that work best, and restructure or terminate what does not. We also argue that a strong and well-focused policy advocacy coalition is needed to help drive reform focused on the social determinants of health. PMID- 22068398 TI - Bringing researchers and community developers together to revitalize a public housing project and improve health. AB - Tens of billions of dollars-both public and private-flow to low-income communities each year, mostly for affordable housing. However, it is rare for the health effects of these investments to be assessed. In San Francisco, California, a collaborative effort is under way that aims to fill this research gap while helping residents of Sunnydale, the city's largest public housing project, where poverty, violence, and truancy are entrenched. The collaboration is in its earliest stages-with construction not scheduled to start for at least four years but some early lessons have emerged. For example, researchers and community developers have found that their data collection needs and timeline expectations often don't match. Nevertheless, the collaborators intend to use the long period before groundbreaking to establish baseline measurements of residents' social and physical well-being, plan initiatives in collaboration with community members and stakeholders, and seek funding for the initiatives and a longitudinal evaluation of the community. PMID- 22068399 TI - At 'Urban Horizons,' healthier living is a beautiful thing. PMID- 22068400 TI - Neighborhood characteristics associated with access to patient-centered medical homes for children. AB - Understanding social determinants of health, such as the social and physical conditions under which children and their families live, work, and play, is essential to reducing disparities and improving the quality of primary care. We studied the relationship between perceptions of neighborhood characteristics such as cohesion, safety, physical environment, and whether children receive care from a patient-centered medical home. We found that place matters. Children were less likely to have access to a medical home if they were from less socially cohesive neighborhoods, less safe neighborhoods, or neighborhoods with fewer amenities. These associations persisted even after adjustment for socioeconomic factors and proved to be more strongly associated than race and income. Our findings underscore the need to foster medical practice models that make use of trusted community partners, such as churches and schools, expand care teams to include community health workers, and identify additional ways to build collaborative relationships between providers and their patients and their families from less cohesive neighborhoods. PMID- 22068401 TI - Community health centers and community development financial institutions: joining forces to address determinants of health. AB - Community health centers and community development financial institutions share similar origins and missions and are increasingly working together to meet community needs. Addressing the social and economic determinants of health is a common focus. The availability of new federal grants and tax credits has led these financial institutions to invest in the creation and expansion of community health centers. This article reviews the most recent trends in these two sectors and explores opportunities for further collaboration to transform the health and well-being of the nation's low-income communities. PMID- 22068402 TI - Training new community health, food service, and environmental protection workers could boost health, jobs, and growth. AB - General job training programs, and separate disease prevention or health promotion programs, are usually viewed as two different strategies for reducing poverty and promoting community development. We propose that with better alignment of the strategies, new jobs with the potential to simultaneously improve population health, lower the cost of health care, and reduce unemployment could be created and filled. Initiatives for three types of entry-level positions in the fields of community health, environmental remediation and protection, and food preparation-show particular promise as vehicles for health and economic improvement at the individual and community levels. Building on current federal programs, new pilot projects financed by federal funding should be created to test and refine such initiatives and their impact and assemble an evidence base for future policy action. PMID- 22068403 TI - Large variations in Medicare payments for surgery highlight savings potential from bundled payment programs. AB - Payers are considering bundled payments for inpatient surgery, combining provider reimbursements into a single payment for the entire episode. We found that current Medicare episode payments for certain inpatient procedures varied by 49 130 percent across hospitals sorted into five payment groups. Intentional differences in payments attributable to such factors as geography or illness severity explained much of this variation. But after adjustment for these differences, per episode payments to the highest-cost hospitals were higher than those to the lowest-cost facilities by up to $2,549 for colectomy and $7,759 for back surgery. Postdischarge care accounted for a large proportion of the variation in payments, as did discretionary physician services, which may be driven in turn by variations in surgeons' practice styles. Our study suggests that bundled payments could yield sizable savings for payers, although the effect on individual institutions will vary because hospitals that were relatively expensive for one procedure were often relatively inexpensive for others. More broadly, our data suggest that many hospitals have considerable room to improve their cost efficiency for inpatient surgery and should look for patterns of excess utilization, particularly among surgical specialties, other inpatient specialist consultations, and various types of postdischarge care. PMID- 22068404 TI - The PROMETHEUS bundled payment experiment: slow start shows problems in implementing new payment models. AB - Fee-for-service payment is blamed for many of the problems observed in the US health care system. One of the leading alternative payment models proposed in the Affordable Care Act of 2010 is bundled payment, which provides payment for all of the care a patient needs over the course of a defined clinical episode, instead of paying for each discrete service. We evaluated the initial "road test" of PROMETHEUS Payment, one of several bundled payment pilot projects. The project has faced substantial implementation challenges, and none of the three pilot sites had executed contracts or made bundled payments as of May 2011. The pilots have taken longer to set up than expected, primarily because of the complexity of the payment model and the fact that it builds on the existing fee-for-service payment system and other complexities of health care. Participants continue to see promise and value in the bundled payment model, but the pilot results suggest that the desired benefits of this and other payment reforms may take time and considerable effort to materialize. PMID- 22068405 TI - The many different prices paid to providers and the flawed theory of cost shifting: is it time for a more rational all-payer system? AB - In developed nations that rely on multiple, competing health insurers-for example, Switzerland and Germany-the prices for health care services and products are subject to uniform price schedules that are either set by government or negotiated on a regional basis between associations of health insurers and associations of providers of health care. In the United States, some states notably Maryland-have used such all-payer systems for hospitals only. Elsewhere in the United States, prices are negotiated between individual payers and providers. This situation has resulted in an opaque system in which payers with market power force weaker payers to cover disproportionate shares of providers' fixed costs-a phenomenon sometimes termed cost shifting-or providers simply succeed in charging higher prices when they can. In this article I propose that this price-discriminatory system be replaced over time by an all-payer system as a means to better control costs and ensure equitable payment. PMID- 22068407 TI - Gaps in residency training should be addressed to better prepare doctors for a twenty-first-century delivery system. AB - Many observers have been concerned about a mismatch between the knowledge, skills, and professional values of newly trained physicians and the requirements of current and future medical practice. We surveyed and interviewed Kaiser Permanente's clinical department chiefs for internal medicine, pediatrics, general surgery, and obstetrics/gynecology to ascertain their views of the perceived gaps in the readiness of newly trained physicians. Nearly half of those surveyed reported deficiencies among new physicians in managing routine conditions or performing simple procedures often encountered in office-based practice. A third of the chiefs noted deficiencies in coordinating care for patients. Filling these and other training gaps will require changes at many levels-from residency programs to Medicare reimbursement policies-to better prepare new physicians for the challenges of working in a health care system evolving to emphasize accountability, quality outcomes, cost control, and information technology. PMID- 22068406 TI - Mayo Clinic employees responded to new requirements for cost sharing by reducing possibly unneeded health services use. AB - Some health plans have experimented with increasing consumer cost sharing, on the theory that consumers will use less unnecessary health care if they are expected to bear some of the financial responsibility for it. However, it is unclear whether the resulting decrease in use is sustained beyond one or two years. In 2004 Mayo Clinic's self-funded health plan increased cost sharing for its employees and their dependents for specialty care visits (adding a $25 copayment to the high-premium option) and other services such as imaging, testing, and outpatient procedures (adding 10 or 20 percent coinsurance, depending on the option). The plan also removed all cost sharing for visits to primary care providers and for preventive services such as colorectal screening and mammography. The result was large decreases in the use of diagnostic testing and outpatient procedures that were sustained for four years, and an immediate decrease in the use of imaging that later rebounded (possibly to levels below the expected trend). Beneficiaries decreased visits to specialists but did not make greater use of primary care services. These results suggest that implementing relatively low levels of cost sharing can lead to a long-term decrease in utilization. PMID- 22068408 TI - How the National Prevention Council can overcome key challenges and improve Americans' health. AB - The Affordable Care Act of 2010 established the first-ever National Prevention, Health Promotion, and Public Health Council out of recognition of the need for a major new national focus on disease prevention. Composed of cabinet-level officials from a range of federal agencies, the council has a clear policy mandate: to coordinate and lead prevention, wellness, and health promotion efforts across the entire federal government and the nation. In its first year, the council developed a comprehensive prevention strategy; but its full implementation is threatened by economic, political, bureaucratic, and institutional challenges. This article examines these challenges and makes recommendations for how to maximize the positive impact of the council through effective cross-agency collaboration aimed at improving Americans' health, including framing prevention as a bipartisan cost containment strategy; distancing the work of the council from the implementation of other aspects of the Affordable Care Act; using dollars from the Prevention and Public Health Fund to incentivize ongoing participation by nonhealth agencies; and providing technical assistance and analytic support to nonhealth agencies willing to broaden attention to the health impacts of their nonhealth policies. PMID- 22068409 TI - Evolving brand-name and generic drug competition may warrant a revision of the Hatch-Waxman Act. AB - The evolution of pharmaceutical competition since Congress passed the Hatch Waxman Act in 1984 raises questions about whether the act's intended balance of incentives for cost savings and continued innovation has been achieved. Generic drug usage and challenges to brand-name drugs' patents have increased markedly, resulting in greatly increased cost savings but also potentially reduced incentives for innovators. Congress should review whether Hatch-Waxman is achieving its intended purpose of balancing incentives for generics and innovation. It also should consider whether the law should be amended so that some of its provisions are brought more in line with recently enacted legislation governing approval of so-called biosimilars, or the corollary for biologics of generic competition for small-molecule drugs. PMID- 22068410 TI - Six climate change-related events in the United States accounted for about $14 billion in lost lives and health costs. AB - The future health costs associated with predicted climate change-related events such as hurricanes, heat waves, and floods are projected to be enormous. This article estimates the health costs associated with six climate change-related events that struck the United States between 2000 and 2009. The six case studies came from categories of climate change-related events projected to worsen with continued global warming-ozone pollution, heat waves, hurricanes, infectious disease outbreaks, river flooding, and wildfires. We estimate that the health costs exceeded $14 billion, with 95 percent due to the value of lives lost prematurely. Actual health care costs were an estimated $740 million. This reflects more than 760,000 encounters with the health care system. Our analysis provides scientists and policy makers with a methodology to use in estimating future health costs related to climate change and highlights the growing need for public health preparedness. PMID- 22068411 TI - Call it 'jiffy boob': what's lacking when care has assembly-line efficiency. PMID- 22068412 TI - Strengthening children's oral health: views from the field. AB - Low-income children and adolescents continue to bear a heavy burden of untreated pain and complications from dental disease. To explore why proposals to remediate this problem have not gained traction, the authors interviewed experts involved in efforts to improve the oral health status of low-income and minority children during the past decade. Key informants believe that success requires addressing both consumer demand and provider supply factors. They especially cite the lack of public outcry for more accessible oral health care and the undervaluing of oral health, relative to medical care. Informants were cautiously optimistic that strategies such as health literacy and outreach campaigns, which have helped increase children's physical activity and improve their diets, offer unexplored opportunities for progress. PMID- 22068414 TI - Appropriate care for chronic pain. PMID- 22068416 TI - Patient-centered medical homes in Michigan. PMID- 22068418 TI - Medicaid managed care for elderly, disabled populations. PMID- 22068420 TI - Withdrawing unsafe drugs from the market. PMID- 22068421 TI - Palliative care and hospice. PMID- 22068422 TI - Parity between behavioral health and medical services. PMID- 22068423 TI - N-cadherin determines individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells in a rat model of myocardial infarction. AB - In this study, we established and characterized human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) from four different donors. However, the hUCB-MSCs showed remarkable variations in their therapeutic efficacy for repairing rat infarcted myocardium (including the process of angiogenesis) 8 weeks after transplantation. In addition, we observed that the level of vascular endothelial growth factor (VEGF) is correlated with the therapeutic efficacy of the four hUCB-MSCs. Next, to investigate the practical application of hUCB-MSCs, we searched for surface signature molecules that could serve as indicators of therapeutic efficacy. The gene for N-cadherin was the only cell surface gene that was highly expressed in the most effective hUCB-MSCs, both at the transcriptional and translational levels. We observed downregulation and upregulation of VEGF in response to N-cadherin blocking and N-cadherin overexpression, respectively. Activation of extracellular signal-regulated kinase (ERK), but not protein kinase B, was increased when N-cadherin expression was increased, whereas disruption of N-cadherin-mediated cell-cell contact induced suppression of ERK activation and led to VEGF downregulation. Moreover, by investigating hUCB-MSCs overexpressing N cadherin or N-cadherin knockdown hUCB-MSCs, we confirmed the in vivo function of N-cadherin. In addition, we observed that DiI-labeled hUCB-MSCs express N cadherin in the peri-infarct area and interact with cardiomyocytes. PMID- 22068424 TI - Safety and tolerability of the Easy VaxTM clinical epidermal electroporation system in healthy adults. AB - DNA vaccines are cost-effective and versatile, though intracellular delivery has been challenging in humans. Alternative delivery modalities such as electroporation have demonstrated improved immune responses, but are painful. In this single-center, double-blind, medical device trial, we evaluated the safety and tolerability of Easy VaxTM dermal electroporation system, alone (without DNA) in healthy adults. Three randomized protocol doses were administered to 10 subjects (80% white, 60% female, mean age: 32.1 years) in each of two areas (total of six doses). Two subjects complained of shooting pain, burning and/or tingling when doses were administered to the forearm region, but not the lateral deltoid regions. Subsequent doses for the remaining eight subjects were restricted to the deltoid regions only. Tolerability pain scores never exceeded 3 of 10 in the 11-Point Pain Rating scale, and 12 of 100 in the Visual Analog Scale (VAS), and lower in follow-up evaluations (P < 0.0001), with no significant difference between the three dosing protocols. Electrical properties of the skin, measured automatically by the device, showed no correlation between pain intensity and skin conductance. In conclusion, the Easy VaxTM electroporation device is safe and well tolerated when administered over the lateral deltoid skin regions in healthy volunteers. PMID- 22068425 TI - Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. AB - Efficient and widespread gene transfer is required for successful treatment of Duchenne muscular dystrophy (DMD). Here, we performed the first clinical trial using a chimeric adeno-associated virus (AAV) capsid variant (designated AAV2.5) derived from a rational design strategy. AAV2.5 was generated from the AAV2 capsid with five mutations from AAV1. The novel chimeric vector combines the improved muscle transduction capacity of AAV1 with reduced antigenic crossreactivity against both parental serotypes, while keeping the AAV2 receptor binding. In a randomized double-blind placebo-controlled phase I clinical study in DMD boys, AAV2.5 vector was injected into the bicep muscle in one arm, with saline control in the contralateral arm. A subset of patients received AAV empty capsid instead of saline in an effort to distinguish an immune response to vector versus minidystrophin transgene. Recombinant AAV genomes were detected in all patients with up to 2.56 vector copies per diploid genome. There was no cellular immune response to AAV2.5 capsid. This trial established that rationally designed AAV2.5 vector was safe and well tolerated, lays the foundation of customizing AAV vectors that best suit the clinical objective (e.g., limb infusion gene delivery) and should usher in the next generation of viral delivery systems for human gene transfer. PMID- 22068426 TI - Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4alpha transduction. AB - Hepatocyte-like cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are expected to be a useful source of cells drug discovery. Although we recently reported that hepatic commitment is promoted by transduction of SOX17 and HEX into human ESC- and iPSC-derived cells, these hepatocyte-like cells were not sufficiently mature for drug screening. To promote hepatic maturation, we utilized transduction of the hepatocyte nuclear factor 4alpha (HNF4alpha) gene, which is known as a master regulator of liver-specific gene expression. Adenovirus vector-mediated overexpression of HNF4alpha in hepatoblasts induced by SOX17 and HEX transduction led to upregulation of epithelial and mature hepatic markers such as cytochrome P450 (CYP) enzymes, and promoted hepatic maturation by activating the mesenchymal-to-epithelial transition (MET). Thus HNF4alpha might play an important role in the hepatic differentiation from human ESC-derived hepatoblasts by activating the MET. Furthermore, the hepatocyte like-cells could catalyze the toxication of several compounds. Our method would be a valuable tool for the efficient generation of functional hepatocytes derived from human ESCs and iPSCs, and the hepatocyte-like cells could be used for predicting drug toxicity. PMID- 22068427 TI - Human skeletal muscle cells with a slow adhesion rate after isolation and an enhanced stress resistance improve function of ischemic hearts. AB - Identification of cells that are endowed with maximum potency could be critical for the clinical success of cell-based therapies. We investigated whether cells with an enhanced efficacy for cardiac cell therapy could be enriched from adult human skeletal muscle on the basis of their adhesion properties to tissue culture flasks following tissue dissociation. Cells that adhered slowly displayed greater myogenic purity and more readily differentiated into myotubes in vitro than rapidly adhering cells (RACs). The slowly adhering cell (SAC) population also survived better than the RAC population in kinetic in vitro assays that simulate conditions of oxidative and inflammatory stress. When evaluated for the treatment of a myocardial infarction (MI), intramyocardial injection of the SACs more effectively improved echocardiographic indexes of left ventricular (LV) remodeling and contractility than the transplantation of the RACs. Immunohistological analysis revealed that hearts injected with SACs displayed a reduction in myocardial fibrosis and an increase in infarct vascularization, donor cell proliferation, and endogenous cardiomyocyte survival and proliferation in comparison with the RAC-treated hearts. In conclusion, these results suggest that adult human skeletal muscle-derived cells are inherently heterogeneous with regard to their efficacy for enhancing cardiac function after cardiac implantation, with SACs outperforming RACs. PMID- 22068428 TI - Oncolytic Sindbis virus targets tumors defective in the interferon response and induces significant bystander antitumor immunity in vivo. AB - Sindbis virus (SBV) has been shown to possess oncolytic potential in many human xenograft tumor models in immunocompromised mice. However, the mechanism underlying the tumor selectivity of SBV remains undetermined. In this study, we provide evidence that the tumor tropism of SBV infection is not determined by the levels of SBV receptor but by the status of the type I interferon (IFN) response in the tumors. Our results demonstrate that cells with defects in the IFN response (in either IFN-beta production or IFN signaling) were highly susceptible to SBV infection in vitro. The results of oncolysis experiments conducted in immunocompetent animals further confirmed that the success of SBV-mediated oncolysis is greatly dependent on the presence of defects in IFN signaling in tumors. In all cases, viral titers rapidly declined in tumors due to host immune responses in immunocompetent animals. Interestingly, however, tumor-specific immune responses were concomitantly elicited, which might contribute to the sustained antitumor effect observed after the clearance of SBV. These findings indicate that SBV-mediated virotherapy is a promising therapeutic strategy for cancers defective in the IFN response and underscore the importance of bystander antitumor immunity in the efficacy of this virotherapy. PMID- 22068430 TI - Understanding pressure ulcer research and education needs: a comparison of the association for the advancement of wound care pressure ulcer guideline evidence levels and content validity scores . AB - Although difficult to quantify due to methodological variations, the worldwide burden of pressure ulcers (PUs) is substantial. Recognizing the importance of providing evidence-based care to help reduce this burden, the North American Wound Care Council societies collaborated to identify PU research and education opportunities using the PU "Guideline of Guidelines" developed and tested by Association for the Advancement of Wound Care Guideline Department (AAWC GD). Volunteer AAWC GD members compiled recommendations from PU guidelines available in 2008, searched the lit- erature for additional research as needed, and developed evidence levels for all recommendations using an established level-of evidence rating scheme. At the same time, AAWC members and Ostomy Wound Management readers were invited via email to participate in a content validation study of the 368 recommendations, rating items on a scale of 1 (not relevant) to 4 (very relevant and succinct). Items with a content validity index (CVI) >0.75 were considered valid. Recommendations with support from two or more randomized controlled PU trials or two or more cohort studies for diagnostic or predictive validity (A-level evidence) and a CVI >75 were grouped as ready for implementation. Recommendations with content validity but without A-level evidence were determined to be opportunities for research; recommendations that lacked content validity but that had A-level evidence were viewed as opportunities for education. Thirty-two (32) multidisciplinary healthcare professionals participated in the content validation study. Most (93.2%) recommendations were rated as valid. Of the 97 (26%) recommendations with A-level evidence, 90 (24.5% of total) met both strong content validity and strong evidence criteria and were rated as ready for implementation as standard of care. Most recommendations (253, 68.8%) were rated as valid but had B- or C-level evidence, representing opportunities for research. Only seven (1.9%) recommendations had a low CVI but A-level evidence, suggesting a need for education. The results show that most of the guideline recommendations are valid, that the number of PU intervention recommendations with A-level evidence is increasing, but that, in general, the need for research to replace opinion with evidence remains high across the entire spectrum of PU prevention and treatment. Understanding what is known (recommendation: ready to implement), what is not known (research needed), and what clinicians need to know (education needed) is an important step toward reducing the burden of pressure ulcers. difficile are warranted. PMID- 22068429 TI - Preclinical corrective gene transfer in xeroderma pigmentosum human skin stem cells. AB - Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (>10(40) cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients. PMID- 22068431 TI - Measuring toe pressures using a portable photoplethysmograph to detect arterial disease in high-risk patients: an overview of the literature. AB - Lower extremity arterial disease (LEAD) is estimated to affect one third of individuals older than 65 years of age, occurs in younger individuals who use tobacco or have diabetes mellitus (DM), and often remains undiagnosed until a patient pres- ents with ischemia-related symptoms or complications. Valid and reliable noninvasive tests such as the ankle-brachial index (ABI) are recommended to detect LEAD. However, ABI results can be inconclusive or the index can be elevated (i.e., >1.3) in persons with calcified ankle arteries due to DM, renal failure, or arthritis. In these instances, obtaining toe pressure (TP) measurements, which correlate well with angiographic findings, is advised, providing the patient does not have vasoconstriction with cold toes or vasospastic disease. In such cases, TP can be obtained using a portable pho- toplethysmograph (PPG), which offers a simple and inexpensive method for healthcare providers in a variety of clinical settings to assess for the presence of LEAD. Portable PPG TP measurements have been found to have a high level of agreement with vascular laboratory PPG tests to detect LEAD, as well as good sensitivity and a high specificity. Adopting a TP measurement protocol of care to assess high-risk individuals such as patients with DM and elevated ABIs potentially can have a major impact on early identification of LEAD and reduce the risk of ischemia-related complications, including lower extremity wounds and amputations. PMID- 22068432 TI - Controversy over the classification of medication-overuse headache. AB - Medication-overuse headache (MOH) is a relatively common and impactful disorder, affecting 1% to 2% of the population, characterized by daily or near-daily headache aggravated by chronic acute medication intake. Primary headache patients do not necessarily develop MOH after acute medication overuse, although a pre existing primary headache is inevitably present. Likewise, headache patients may deteriorate in terms of frequency without medication overuse, or suffer from chronic headache in the presence of drug abuse without any causal relationship. To classify and define diagnostic criteria for MOH in the absence of objective biomarkers is a difficult task that is presently based on clinical grounds and is limited in part by the relative lack of research in this field. The present criteria are less restrictive but also less precise than the previous versions because they allow the diagnosis without the previously required MOH confirmation after medication withdrawal. MOH should remain as a distinct secondary disorder based on the available clinical and pathophysiological evidence. PMID- 22068433 TI - Robotic-assisted percutaneous coronary intervention--filling an unmet need. AB - Percutaneous coronary intervention (PCI) has undergone a remarkable evolution over the past 25 years. Initially, the procedure was limited to relatively straightforward lesions and was associated with significant risk and unpredictable long-term efficacy. With the incorporation of new technologies such as stents, the safety and efficacy of the procedure has improved dramatically. However, the fundamental way in which the procedure is performed has changed little since the time of Gruntzig's first successful case. Cumulative exposure to ionizing radiation, orthopedic injuries resulting from wearing shielding aprons, and fatigue from standing for hours at the table have made the catheterization laboratory a "high-risk workplace" for the interventional cardiologist. Robotic assisted PCI was developed to allow the operator to precisely manipulate angioplasty guidewires, balloons, and stents from a radiation-shielded cockpit. A small first-in-man study demonstrated that PCI can be performed with robotic assistance. The pivotal Percutaneous Robotically Enhanced Coronary Intervention Study trial is currently enrolling patients and evaluating the safety and efficacy of the CorPath(r) robotically assisted PCI system. PMID- 22068434 TI - 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. PMID- 22068435 TI - 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. PMID- 22068436 TI - Flexible oligocholate foldamers as membrane transporters and their guest dependent transport mechanism. AB - Dimeric, trimeric, and tetrameric oligocholates with flexible 4-aminobutyroyl spacers caused the efflux of hydrophilic molecules such as carboxyfluorescein (CF) and glucose from POPC/POPG liposomes. Transport was greatly suppressed across higher-melting DPPC membranes. Lipid-mixing assays and dynamic light scattering (DLS) indicated that the liposomes were intact during the transport. Kinetic analysis supported the involvement of monomeric species in the rate limiting step of CF transport, consistent with a carrier-based mechanism. Glucose transport, on the other hand, displayed a highly unusual zero-order dependence on the oligocholate concentration at low loading of the transporter. Different selectivity was observed in the oligocholate transporters depending on the guest involved. PMID- 22068437 TI - Enzyme Directed Templating of Artificial Bone Mineral. AB - Bone is one of Nature's most remarkable materials, not only for its mechanical properties but also for its ability to repair fractures and remodel its microstructure in response to stress. At the nanoscale bone is a supramolecular matrix of collagen fibers reinforced by hydroxyapatite crystals with a high degree of order. Emulating elements of the biological synthesis of this composite could help develop strategies for advanced materials. Previous work has demonstrated the use of functionalized peptide amphiphile nanofibers in a two dimensional system to emulate hydroxyapatite mineralization in natural bone. We describe here an artificial, in vitro biomineralization process that allows a similar process to occur in three dimensions. The system employs the natural enzyme alkaline phosphatase and a phosphorylated, anionic nanofiber gel matrix to template hydroxyapatite nanocrystals with size, shape, and crystallographic orientation resembling natural bone mineral. The formation of this biomimetic mineral in three dimensions results from the synergy of fiber-induced nucleation and the temporal control of phosphate ion harvesting by the enzyme. Gradual enzymatic harvesting of ions for crystal growth and the strong nucleating ability of the phosphorylated fibers suppresses uncontrolled precipitation of mineral. The strategy could lead to biomimetic materials to promote bone regeneration or the synthesis of hybrid materials with crystallographically defined structures. PMID- 22068440 TI - Itch and pain in adolescents are associated with suicidal ideation: a population based cross-sectional study. AB - The association between itch and suicidal ideation has not been explored previously in the general population. The aim of the present study is to analyse the association between itch and suicidal ideation in adolescents, and to compare the findings with an expected association between pain and suicidal ideation in the same sample. A total of 4,744 adolescents were invited to join the questionnaire-based study. The participation rate was 80%. The prevalence of suicidal ideation among those who reported no itch was 8.4% vs 21.1% among those who reported severe itch. Significant association between itch and suicidal ideation was found in a multivariate model (odds ratio 3.0, 95% confidence interval (CI) 2.1-4.2) and between pain and suicidal ideation (odds ratio 3.8, 95% CI 2.6-5.7). The findings were similar and statistically significant in girls and boys separately. Itch and pain are approximately equally strongly associated with suicidal ideation in a large general population of adolescents. PMID- 22068439 TI - Expressed sequence-tag analysis of ovaries of Brachiaria brizantha reveals genes associated with the early steps of embryo sac differentiation of apomictic plants. AB - In apomixis, asexual mode of plant reproduction through seeds, an unreduced megagametophyte is formed due to circumvented or altered meiosis. The embryo develops autonomously from the unreduced egg cell, independently of fertilization. Brachiaria is a genus of tropical forage grasses that reproduces sexually or by apomixis. A limited number of studies have reported the sequencing of apomixis-related genes and a few Brachiaria sequences have been deposited at genebank databases. This work shows sequencing and expression analyses of expressed sequence-tags (ESTs) of Brachiaria genus and points to transcripts from ovaries with preferential expression at megasporogenesis in apomictic plants. From the 11 differentially expressed sequences from immature ovaries of sexual and apomictic Brachiaria brizantha obtained from macroarray analysis, 9 were preferentially detected in ovaries of apomicts, as confirmed by RT-qPCR. A putative involvement in early steps of Panicum-type embryo sac differentiation of four sequences from B. brizantha ovaries: BbrizHelic, BbrizRan, BbrizSec13 and BbrizSti1 is suggested. Two of these, BbrizSti1 and BbrizHelic, with similarity to a gene coding to stress induced protein and a helicase, respectively, are preferentially expressed in the early stages of apomictic ovaries development, especially in the nucellus, in a stage previous to the differentiation of aposporous initials, as verified by in situ hybridization. PMID- 22068441 TI - Slowing down after a mild traumatic brain injury: a strategy to improve cognitive task performance? AB - Long-term persistent attention and memory difficulties following a mild traumatic brain injury (TBI) often go undetected on standard neuropsychological tests, despite complaints by mild TBI individuals. We conducted a visual Repetition Detection working memory task to digits, in which we manipulated task difficulty by increasing cognitive load, to identify subtle deficits long after a mild TBI. Twenty-six undergraduate students with a self-report of one mild TBI, which occurred at least 6 months prior, and 31 non-head-injured controls took part in the study. Participants were not informed until study completion that the study's purpose was to examine cognitive changes following a mild TBI, to reduce the influence of "diagnosis threat" on performance. Neuropsychological tasks did not differentiate the groups, though mild TBI participants reported higher state anxiety levels. On our working memory task, the mild TBI group took significantly longer to accurately detect repeated targets on our task, suggesting that slowed information processing is a long-term consequence of mild TBI. Accuracy was comparable in the low-load condition and, unexpectedly, mild TBI performance surpassed that of controls in the high-load condition. Temporal analysis of target identification suggested a strategy difference between groups: mild TBI participants made a significantly greater number of accurate responses following the target's offset, and significantly fewer erroneous distracter responses prior to target onset, compared with controls. Results suggest that long after a mild TBI, high-functioning young adults invoke a strategy of delaying their identification of targets in order to maintain, and facilitate, accuracy on cognitively demanding tasks. PMID- 22068442 TI - Are embedded validity indices equivalent to free-standing symptom validity tests? AB - Symptom validity assessment is an important part of neuropsychological evaluation. There are currently several free-standing symptom validity tests (SVTs), as well as a number of empirically derived embedded validity indices, that have been developed to assess that an examinee is putting forth an optimal level of effort during testing. The use of embedded validity indices is attractive since they do not increase overall testing time and may also be less vulnerable to coaching. In addition, there are some instances where embedded validity indices are the only tool available to the neuropsychological practitioner for assessing an examinee's level of effort. As with free-standing measures, the sensitivity and specificity of embedded validity indices to suboptimal effort varies. The present study evaluated the diagnostic validity of 17 embedded validity indices by comparing performance on these indices to performance on combinations of free-standing SVTs. Results from the current medico-legal sample revealed that of the embedded validity indices, Reliable Digit Span had the best classification accuracy; however, the findings do not support the use of this embedded validity index in the absence of free-standing SVTs. PMID- 22068443 TI - [The concept of early vascular aging - a story from EVA and ADAM]. PMID- 22068444 TI - [Effects of daily physical exercise at school on cardiovascular risk--results of a 2-year cluster-randomized study]. AB - BACKGROUND AND OBJECTIVE: It was the aim of this study to measure the effects over two years of daily sport activity during the school-day on their physical fitness (primary endpoint), motor coordination and blood pressure (secondary endpoints). METHODS: A total of 232 children from eleven different 6 (th) grade classes were enrolled after informed parental consent. Their mean age was 11.1 +/- 0.6 years. Six classes were randomly assigned for intervention (n=141), five as control (n=91). Those of the intervention cohort undertook, for five days weekly during the school year one hour of regulated sport exercise, including 15 min of endurance training. The pupils of the control group undertook customary sport activity (two hours a week). Anthropometric data were recorded and maximal oxygen uptake measured in each pupil, as well as blood pressure and motor coordination at the beginning and at the end of each of the two years of the study. The data were analyzed using the cluster randomization method. RESULTS: Maximal oxygen uptake (VO (2)max) had improved among the intervention group after two years, compared with the controls (3.12 m/kg/min, 95% confindence interval [CI] 0.06-6.19), while improvement in motor coordination just failed to reach statistical significance (3.06, 95% CI -0.17-6.29). There was no significant difference in systolic and diastolic blood pressure, but a downward trend in the prevalence of overweight and obesity from 12.1% to 7.8% in the intervention group. CONCLUSION: The results indicate that daily physical exercise during school hours should be given greater importance. But it will require a long-term trial to determine whether promotion of increased physical activity at school influences the prevalence of cardiovascular risk factors when the pupils reach adulthood. PMID- 22068445 TI - [Retinal microangiopathy in arterial hypertension as an early marker of a cerebral macroangiopathy]. AB - HISTORY AND ADMISSION FINDINGS: A 54-year-old man reported having had nonspecific attacks of dizziness. His BMI was 27.7. Since 11 years he had been treated for arterial hypertension and had received oral medication for type 2 diabetes for one year. The latest blood pressure value was 134/109 mm Hg during treatment with a combination of atenolol, chlortalidone und hydralazine-HCl; furthermore hr received simvastatin, metformin, glimepirid und ramipril. A standardized telemedical imaging of the retina ("talkingeyes ((r)) ") was undertaken, revealing focal and generalized arteriolar narrowing of the retinal vessels and a retinal microinfarction (cotton wool spot) in the right eye. The arterial/venous ratio was decreased to 0.74 in the right and 0.77 in the left eye. INVESTIGATIONS: Optical coherence tomographie (OCT) revealed an ischemic microinfarction of the retina with marked axonal swelling. The digital subtraction angiography of the cerebral vessels revealed a 40 % stenosis of the right internal carotid artery and a proximal, highgrade stenosis of the basilary artery. TREATMENT AND COURSE: Angioplasty with stent insertion of the basilary artery was performed. Long-term observation showed no restenosis and a reduction in the size of the the retinal microinfarct. CONCLUSION: Retinal microinfarctions denote localized retinal areas of hypoxia and underperfusion. They may act as markers of a generalized micro- and macroangiopathy. Patients with severe retinal microangiopathic changes should be examined thoroughly to detect early macroangiopathic changes. These can be treated by interventional procedures thus avoiding irreversible end-organ damages. PMID- 22068446 TI - [54-year-old man with ICD and increasing dyspnea]. PMID- 22068447 TI - [Blood pressure variability]. PMID- 22068448 TI - [Vascular aging, arterial hypertension and physical activity]. AB - The present review delineates the significance of intima-media-thickness, arterial stiffness and endothelial function for vascular aging. There is profound evidence for an increase in intima-media-thickness and vascular stiffness not only during healthy aging but induced also by cardiovascular risk factors. There is a central role of arterial hypertension for this progression in both structural factors. In addition, both parameters are strongly associated with cardiovascular risk. Endothelial function measured as postischemic flow-mediated vasodilatation is a functional parameter which is decreased both in healthy aging and by cardiovascular risk factors. Physical activity modifies the influence of aging and risk factors on endothelial function. A positive influence of endurance exercise on vascular stiffness and endothelial function has been demonstrated in numerous studies. In long-term studies, regular physical activity has been shown to reduce the progression of intima-media-thickness. Thus, arterial hypertension accelerates vascular aging, while physical activity has a positive influence on a variety of vascular parameters associated with vascular aging. PMID- 22068449 TI - [Pulse wave analysis and central (aortic) pressure measurement: for use in reality? - Pro]. PMID- 22068450 TI - [Pulse wave analysis and central (aortic) pressure measurement: for use in reality? - Contra]. PMID- 22068451 TI - [Practice guidelines for home blood pressure measurement]. PMID- 22068452 TI - [On the value of diuretics for hypertension treatment]. PMID- 22068453 TI - [Gout - regardless of therapeutic options a "forgotten" disease]. PMID- 22068454 TI - Green chemistry: solvent- and metal-free Prins cyclization. Application to sequential reactions. AB - Prins cyclization between a homoallylic alcohol and an aldehyde, promoted by trimethylsilyl halide, afforded 4-halo-tetrahydropyrans with good to excellent yields. Thanks to the absence of the solvent and metal, the THP thus obtained have been implicated without purification in several other reactions, in a sequential way, affording in particular new indole derivatives. PMID- 22068455 TI - Effect of dietary mannan oligosaccharide (MOS) on growth performance, survival, body composition, and some hematological parameters in giant sturgeon juvenile (Huso huso Linnaeus, 1754). AB - The effect of dietary mannan oligosaccharide (MOS; activeMOS(r)) on growth, survival, and body composition in giant sturgeon juvenile (Huso huso) with initially average weight 46.89 +/- 2.57 was investigated for a period of 46 days. Basal diet were supplemented with 0 (control), 2, and 4 g kg(-1) MOS in a totally randomized design trial in triplicate groups. The results showed no significant differences in growth and feeding parameters between control and treatment groups (MOS supplementation diets) (P > 0.05). There was a statistically significant decrease (P < 0.05) in feed per fish level in only group treated with 4 g kg(-1) MOS. The highest and the lowest growth performances were observed in 2 and 4 g kg(-1) MOS, respectively. There were no significant differences in survival rate among all treatment groups (P > 0.05). In group treated with 2 g kg(-1) MOS was a significant difference in lipid carcass (P < 0.05), whereas protein, ash, and moisture remained unaffected (P > 0.05). However, no significant difference was observed in intestinal lactic acid bacteria between all treatment groups (P > 0.05). There were no significant differences in hematological parameters between control and MOS treatment groups (P > 0.05). These results suggested that the prebiotic mannan oligosaccharide did not influence the growth performance in giant sturgeon juvenile, and it is not appropriate for supplementation in the diet of cultured juvenile giant sturgeon. PMID- 22068456 TI - Purification and characterization of trypsin from the pyloric ceca of orange spotted grouper, Epinephelus coioides. AB - Trypsin from the pyloric ceca of orange-spotted grouper, Epinephelus coioides, was purified by fractionation with ammonium sulfate, ionic exchange, and affinity chromatography. The protein was purified 161.85-fold with a yield of 4%. Purified trypsin had an apparent molecular weight of 24 kDa according to an SDS-PAGE analysis. Optimal profiles of temperature and pH of the enzyme were 50 degrees C and 8-10, respectively, using Nalpha-benzoyl-L: -arginine ethyl ester as the substrate. The results of thermal and pH stability assays showed that the enzyme was stable at temperatures of up to 50 degrees C and in the pH range of 6-8. Trypsin activity decreased with an increasing NaCl concentration (0-0.6 M). The activity of purified trypsin was effectively inhibited by a soybean trypsin inhibitor and N-p-tosyl-L: -lysine chloromethyl ketone, and was slightly inhibited by iodoacetic acid, ethylenediaminetetraacetic acid, 1-(L: -trans epoxysuccinyl-leucylamino)-4-guanidinobutane, and pepstatin A. Protein identification of the purified protease showed that the sequences of two peptides, LGEHNI and NLDNDIML, were highly homologous to other fish trypsins. The measurement of trypsin activity in different tissues showed that the highest activity was detected in pyloric ceca, followed by anterior intestine, middle intestine, hind intestine and spleen, but very low activities were found in other tissues. An inverse relationship between the trypsin activity in four tissues of pyloric ceca, anterior intestine, middle intestine and hind intestine and fish body weight as a result of increased pepsin in stomach indicated grouper growth status was increased. PMID- 22068457 TI - Preclinical study of the DNA repair inhibitor Dbait in combination with chemotherapy in colorectal cancer. AB - BACKGROUND: Dbait molecules are a new class of DNA repair inhibitors triggering false DNA damage signaling in cancer cells. Dbait has already been shown to be effective in combination with radiotherapy. The aim of this study was to assess the adjuvant impact of Dbait on chemotherapy in vitro and in mouse models of colorectal cancer. METHODS: We assessed DNA repair efficiency over time, in vitro, in human colon adenocarcinoma HT-29 (wild-type KRAS) and HCT-116 (mutated KRAS) cell lines treated with Dbait in combination with 5-fluorouracil and/or camptothecin. Genetically engineered mice spontaneously developing colorectal tumors in the intestines were selected for the evaluation of treatment efficacy. RESULTS: Dbait delayed the repair of DNA damage induced by chemotherapy in vitro. In APC (+/1638N) mutant mice, the combination of Dbait and chemotherapy decreased tumor size more effectively than chemotherapy alone (median size: 3.6 vs. 10.85 mm(2), P < 0.05). In APC (+/1638N)/KRAS ( V12G ) mutant mice, animals treated with a combination of Dbait and chemotherapy survived significantly longer than animals treated by chemotherapy alone (median survival: 210 vs. 194 days, P < 0.05). A quarter of all the animals treated by chemotherapy alone died as rapidly as untreated animals, whereas the first death was delayed by 29 days by the addition of Dbait. No increase in toxicity due to Dbait was observed in either mouse model. CONCLUSIONS: The use of Dbait to inhibit DNA repair may be an effective additional treatment for increasing the efficacy of chemotherapy in colon or rectal cancer, independently of KRAS status. PMID- 22068458 TI - Interaction between anions and substituted molecular bowls. AB - Complexes formed by anions and substituted molecular bowls were studied by means of computational methods. The bowls consisted of corannulene molecules substituted with five or ten F, Cl, or CN groups, whereas Cl(-), Br(-) and BF(4)( ) were the anions considered. Substitution with F, Cl and CN hardly affects the geometry of the bowl, but produces an inversion of the molecular electrostatic potential of the bowls, which becomes positive over the two faces of the bowl, therefore interacting favorably with anions. In all cases considered, the most stable complex presents the anion interacting with the concave side of the bowl. The strength of the interaction roughly follows the values of molecular electrostatic potential, being more stable as more positive is the potential. The preference of anions to interact with the concave side of the bowls has its origin in stronger electrostatic and dispersion interactions. Though the solvent produces an important decrease in the stability of the complexes, the results suggest the possibility of employing these substituted buckybowls as anion receptors with a preferential concave complexation, especially for large anions. PMID- 22068461 TI - Differential effects of AMPA receptor potentiators and glycine reuptake inhibitors on antipsychotic efficacy and prefrontal glutamatergic transmission. AB - RATIONALE: The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor positive allosteric modulators (AMPA-PAMs), Org 24448 and Org 26576, and the glycine transporter-1 (GlyT-1) inhibitor Org 25935 are developed for treatment of schizophrenia. OBJECTIVES: Here we examined experimentally the ability of co-administration of these AMPA-PAMs or the GlyT-1 inhibitor to augment the antipsychotic activity and effect on cortical N-methyl-D: -aspartate (NMDA) receptor-mediated transmission of risperidone, olanzapine, or haloperidol. METHODS: We examined antipsychotic efficacy using the conditioned avoidance response (CAR) test, extrapyramidal side effect liability using a catalepsy test, and cortical NMDA receptor-mediated glutamatergic transmission using intracellular electrophysiological recording technique in vitro. RESULTS: Both AMPA-PAMs enhanced the suppression of CAR induced by risperidone or olanzapine, and Org 24448 also enhanced the effect of haloperidol. In contrast, the GlyT-1 inhibitor did not cause any behaviorally significant effect in the CAR test. However, the GlyT-1 inhibitor, but not the AMPA-PAMs, produced a large facilitation of NMDA-induced currents. All three drugs potentiated the effect of risperidone but not haloperidol on these currents. The GlyT-1 inhibitor also facilitated the effect of olanzapine. All drugs potentiated the effect of risperidone on electrically stimulated excitatory postsynaptic potentials (EPSP) in cortical pyramidal cells, whereas only the GlyT inhibitor facilitated the effect of olanzapine. CONCLUSIONS: Our results suggest that the AMPA-PAMs, when compared to the GlyT-1 inhibitor, show differential effects in terms of augmentation of antipsychotic efficacy, particularly when combined with risperidone or olanzapine. Both AMPA-PAMs and the GlyT-1 inhibitor may also improve negative symptoms and cognitive impairments in schizophrenia, in particular when combined with risperidone. PMID- 22068463 TI - Locoregional recurrence risk factors in breast cancer patients with positive axillary lymph nodes and the impact of postmastectomy radiotherapy. AB - BACKGROUND: Locoregional recurrence (LRR) after mastectomy reduces the patient's quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps establish locoregional control and reduces LRR in patients with >=4 metastatic nodes. However, in patients with 1-3 metastatic nodes, the incidence of LRR and the role of PMRT have been the subject of substantial controversy. This study assessed the risk factors for LRR and the efficacy of PMRT in Japanese breast cancer patients with metastatic nodes. METHODS: This study analyzed 789 cases of invasive breast carcinoma with metastatic nodes from 1998 to 2008. We divided the study population into 4 groups: 1-3 positive nodes with/without chemotherapy and >=4 positive nodes with/without chemotherapy. Risk factors for LRR were identified and the relationship between LRR and PMRT was analyzed. RESULTS: During the median follow up of 59.6 months, 61 (7.7%) patients experienced LRR. In patients who received chemotherapy, independent LRR risk factors were high nuclear grade, severe lymphatic invasion, vascular invasion, and progesterone receptor-negative status in patients with 1-3 positive nodes, and severe lymphatic invasion and estrogen receptor-negative status in patients with >=4 nodes. Although patients treated with PMRT had good outcomes, there was no significant difference, and PMRT did not significantly improve the outcome of the patients with all risk factors. CONCLUSIONS: With systemic therapy and adequate dissection, PMRT by itself was of limited value in establishing locoregional control. The indication for PMRT in patients with 1-3 positive nodes remains controversial. PMID- 22068462 TI - Metabolic oligosaccharide engineering with N-Acyl functionalized ManNAc analogs: cytotoxicity, metabolic flux, and glycan-display considerations. AB - Metabolic oligosaccharide engineering (MOE) is a maturing technology capable of modifying cell surface sugars in living cells and animals through the biosynthetic installation of non-natural monosaccharides into the glycocalyx. A particularly robust area of investigation involves the incorporation of azide functional groups onto the cell surface, which can then be further derivatized using "click chemistry." While considerable effort has gone into optimizing the reagents used for the azide ligation reactions, less optimization of the monosaccharide analogs used in the preceding metabolic incorporation steps has been done. This study fills this void by reporting novel butanoylated ManNAc analogs that are used by cells with greater efficiency and less cytotoxicity than the current "gold standard," which are peracetylated compounds such as Ac4 ManNAz. In particular, tributanoylated, N-acetyl, N-azido, and N-levulinoyl ManNAc analogs with the high flux 1,3,4-O-hydroxyl pattern of butanoylation were compared with their counterparts having the pro-apoptotic 3,4,6-O-butanoylation pattern. The results reveal that the ketone-bearing N-levulinoyl analog 3,4,6-O Bu3 ManNLev is highly apoptotic, and thus is a promising anti-cancer drug candidate. By contrast, the azide-bearing analog 1,3,4-O-Bu3 ManNAz effectively labeled cellular sialoglycans at concentrations ~3- to 5-fold lower (e.g., at 12.5-25 uM) than Ac4 ManNAz (50-150 uM) and exhibited no indications of apoptosis even at concentrations up to 400 uM. In summary, this work extends emerging structure activity relationships that predict the effects of short chain fatty acid modified monosaccharides on mammalian cells and also provides a tangible advance in efforts to make MOE a practical technology for the medical and biotechnology communities. PMID- 22068464 TI - Can docetaxel therapy improve overall survival from primary therapy compared with androgen-deprivation therapy alone in Japanese patients with castration-resistant prostate cancer? A multi-institutional cooperative study. AB - BACKGROUND: To verify the actual clinical benefit of docetaxel (DOC) therapy and to explore the prognostic factors that may predict overall survival in Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: Baseline characteristics-matched CRPC patients who received conventional androgen deprivation therapy (ADT) or ADT plus DOC were compared retrospectively. The primary endpoint was overall survival (OS) from primary therapy. Secondary endpoints were response of tumor(s), prostate-specific antigen (PSA) levels, and toxicity. RESULTS: Median OS was significantly longer in the DOC group (n = 117) than the control group (n = 118) (94.0 vs. 70.0 months, P = 0.0077) and the corresponding hazard ratio (HR) for death in DOC group was 0.566 [95% confidence interval (95%CI) 0.370-0.867; P = 0.0088]. Effective DOC groups [medium dose (50 69 mg/m(2)) and high dose (>=70 mg/m(2))] had significantly longer median OS than control even when survival times were calculated from the start of castration resistant events (151 vs. 36 months; P = 0.0173) and the corresponding HR for death in the DOC group was 0.515 (95%CI 0.293-0.903; P = 0.0205). In multivariate analysis, statistically significant prognostic indicators were Gleason score, time to CRPC events, and receipt of DOC therapy. Response rate of both measurable lesion and PSA was not significantly different between each DOC dose group. Grade 3 or 4 adverse events associated with low- [30-49 mg/m(2)], medium-, and high dose DOC were 21.9, 35.7, and 90.7%, respectively. No death due to DOC therapy was reported. CONCLUSION: Treatment with DOC improves OS from primary therapy compared with conventional ADT alone in Japanese patients with CRPC. PMID- 22068459 TI - Spontaneous object recognition and its relevance to schizophrenia: a review of findings from pharmacological, genetic, lesion and developmental rodent models. AB - RATIONALE: Spontaneous (novel) object recognition (SOR) is one of the most widely used rodent behavioural tests. The opportunity for rapid data collection has made SOR a popular choice in studies that explore cognitive impairment in rodent models of schizophrenia, and that test the efficacy of drugs intended to reverse these deficits. OBJECTIVES: We provide an overview of the many recent studies that have used SOR to explore the mnemonic effects of manipulation of the key transmitter systems relevant to schizophrenia-the dopamine, glutamate, GABA, acetylcholine, serotonin and cannabinoid systems-alone or in combination. We also review the use of SOR in studying memory in genetically modified mouse models of schizophrenia, as well as in neurodevelopmental and lesion models. We end by discussing the construct and predictive validity, and translational relevance, of SOR with respect to cognitive impairment in schizophrenia. RESULTS: Perturbation of the dopamine or glutamate systems can generate robust and reliable impairment in SOR. Impaired performance is also seen following antagonism of the muscarinic acetylcholine system, or exposure to cannabinoid agonists. Cognitive enhancement has been reported using alpha7-nicotinic acetylcholine receptor agonists and 5 HT(6) antagonists. Among non-pharmacological models, neonatal ventral hippocampal lesions and maternal immune activation can impair SOR, while mixed results have been obtained with mice carrying mutations in schizophrenia risk-associated genes, including neuregulin and COMT. CONCLUSIONS: While SOR is not without its limitations, the task represents a useful method for studying manipulations with relevance to cognitive impairment in schizophrenia, as well as the interactions between them. PMID- 22068465 TI - Randomized controlled study of natural interferon alpha as adjuvant treatment for stage II or III renal cell carcinoma. AB - BACKGROUND: The prophylactic effect of postoperative interferon on recurrence and distant metastasis in stage II or III renal cell carcinoma is unclear. In most studies, interferon has been administered for 6 months or less. Therefore, we performed a clinical study of the efficacy of 1-year postoperative administration of natural interferon alpha, which is generally used in Japan. METHODS: The subjects were patients diagnosed with stage II or III renal cell carcinoma who underwent radical nephrectomy. The subjects were randomly allocated to receive an intramuscular injection of natural interferon alpha (3 million to 6 million units) 3 times a week for 1 year or to receive follow-up observation until recurrence or metastasis occurred. Chest and abdominal CT were performed once yearly for all patients. The primary endpoint was progression-free survival. RESULTS: From September 2001 to August 2006, a total of 107 patients were registered, but 7 subsequently withdrew from the study. Therefore, 100 patients were included in the analysis. The primary endpoint of progression-free survival did not differ significantly between the groups that received natural interferon alpha or follow-up observation (p = 0.456, log-rank test). However, peak hazards of progression in the interferon group were delayed for about 6-10 months compared with the observation group. CONCLUSION: Progression-free survival showed no improvement after administration of natural interferon alpha to patients with stage II or III renal cell carcinoma for 1 year after radical nephrectomy. The peak hazards of progression might be delayed by about 6 months by interferon administration. PMID- 22068466 TI - [Muscle disease update: advance in the first decade of 21 century]. PMID- 22068467 TI - [Myotonic dystrophy type 2]. AB - Myotonic dystrophies (DMs) are autosomal dominant disorders with multisystemic clinical features. DMs are categorized as DM1, caused by a (CTG)n expansion mutation in 19q13, and DM2, caused by a (CCTG)n expansion mutation in 3q21. The clinical features of DM2 are diffuse and proximal dominant weakness, wasting, myotonia, cardiac problems, cataracts, and insulinresistance. DM2 is milder than DM1. We compared the clinical features of both DMs and studied a Japanese patient with DM2 who had expansion mutations different from those usually attributed to the disease and originally discovered by European researchers. The detailed clinical features of the Japanese DM2 patient are described. PMID- 22068468 TI - [Myotonic dystrophy: therapeutic approaches to RNA toxicity]. AB - Myotonic dystrophy (DM) is the most common hereditary muscle disease in adults, caused by unstable genomic expansions of simple sequence repeats. The mutant RNA transcripts containing the expanded repeat give rise to a toxic gainoffunction by perturbing splicing factors in the nucleus, leading to the misregulation of alternative pre-mRNA splicing. Although no curative treatment exists, recent advances in research and pharmaceutical technology have provided clues for therapeutic intervention in DM. Herein, we review the RNA-dominant mechanism of DM and potential therapeutic approaches for degrading or neutralizing the toxic RNA, restoring splicing factors, correcting splicing misregulation, and stabilizing the repeat. PMID- 22068469 TI - [Collagen VI-related muscle disorders]. AB - Collagen VI-related muscle disorders include severe Ullrich's disease (Ullrich congenital muscular dystrophy:UCMD) and milder Bethlem myopathy. Mutations in the 3 collagen VI genes, namely, COL6A1, COL6A2, and COL6A3, cause both diseases. UCMD is inherited in an autosomal recessive manner, and de novo dominant mutations are also reported. Bethlem myopathy is usually inherited in an autosomal dominant manner, but a rare autosomal recessive inheritance has recently been reported. Patients with UCMD have generalized muscle weakness, multiple contractures of the proximal joints, and hyperextensibility of the distal joints. Bethlem myopathy is characterized by a combination of proximal muscle weakness and contractures of finger, elbow, and ankle joints. Because intermediate phenotypes occur, UCMD and Bethlem myopathy should be considered diseases in a continuous spectrum of collagen VI-related muscle disorders. Abnormalities of cell adhesion, regeneration, mitochondrial permeability transition pore, and autophagy have been reported in UCMD. Respiratory surveillance for nocturnal hypoventilation and proper respirator implementation are crinical management considerations in UCMD. Orthopedic assessment in necessary if surgery for Achilles tendon contractures is being considered in patient with Bethlem myopathy. We evaluated the role of nonsense-mediated mRNA decay (NMD) in UCMD associated with a premature termination codon in the COL6A2 gene, which caused the loss of collagen VI. A pharmacological block of NMD caused upregulation of the mutant collagen VI and partially functional extracellular matrix formation. Cyclosporin A has been reported to correct mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies, and a pilot trial of cyclosporin A was carried out. PMID- 22068470 TI - [Myofibrillar myopathy]. AB - Myofibrillar myopathy (MFM) describes a group of hereditary myopathies pathologically characterized as markedly disorganized myofibrils with cytoplasmic inclusions. Seven disease-related genes have been identified, including DES, CRYAB, MYOT, ZASP, FLNC, BAG3, and FHL1, all of which encode proteins closely related to Z-line. MFM often occurs via autosomal dominant inheritance, but autosomal recessive, or X-linked, forms are also seen. The majority of Japanese patients have no family history. Clinical symptoms of MFM are quite variable. The age at onset ranges from infancy to the eighth decade of life. Some patients show limb girdle muscle involvement, whereas others show distal myopathy. Patients who have cardiomyopathy with no obvious muscle weakness are also seen. Skeletal muscles from MFM patients contain cytoplasmic inclusions called cytoplasmic or spheroid bodies. Immunohistochemically, cytoplasmic accumulations of various proteins are commonly seen, including Z-line proteins such as desmin, alphaB crystallin, and myotilin; membrane proteins such as dystrophin and sarcoglycans; heat shock proteins; and ubiquitin. We review the clinical, pathological, and genetic characteristics of MFM patients, including those from our recent study results. Despite intensive mutation screening, about 70% of MFM patients in our series had no mutation in the known causative genes. The identification of novel disease-related genes and the development of efficient diagnostic tools are urgently needed, as is the elucidation of the pathomechanism of myofibril disorganization as a possible target for new treatments. PMID- 22068471 TI - [Recent Advances in alpha-dystroglycanopathy]. AB - Fukuyama-type congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB), and Walker-Warburg syndrome (WWS) are autosomal recessive disorders characterized by congenital muscular dystrophy with structural brain and eye abnormalities. Aberrant glycosylation of alpha-dystroglycan (alpha-DG) is a common pathomechanism of these disorders. In addition, genetic and glycobiological evidence has shown that abnormal glycosylation of alpha-DG is also seen in several forms of congenital and limb-girdle-type muscular dystrophies. These disorders are collectively called "alpha-dystroglycanopathy" and nowadays, this term is widely accepted because it is useful for illustrating a complicated genotype-phenotype correlation of these disorders. alpha-DG is a membrane-associated protein that interacts with extracellular matrix proteins such as laminin, and abnormal glycosylation of alpha-DG results in loss of its laminin-binding activity. A number of serine/threonine residues are present in the mucin-like domain of alpha-DG and are majorly composed of sugar chains. Among these glycans, an O-mannosyl tetrasaccharide (Neu5Ac-alpha2,3-Gal-beta1,4-GlcNAc beta1,2-Man) is important for laminin-binding activity of alpha-DG. POMT1/2 and POMGnT1, protein products of causative genes of WWS and MEB, respectively, are enzymes that directly catalyze the biosynthesis of this glycan. Recent studies have suggested that a phosphodiester-linked structure on O-mannose is also important for the laminin-binding activity and that mutations in other causative genes of alpha-dystroglycanopathy, such as fukutin (originally identified as the gene responsible for FCMD) and LARGE, disrupt the post-phosphoryl structure. Here, we review the history of basic and clinical research on alpha dystroglycanopathy and refine its clinical spectrum, which should be broadly extended. In addition, we reveal some progress in research on alpha dystroglycanopathy including a novel disease mechanism and anti-sense oligonucleotide therapy for FCMD. PMID- 22068472 TI - [Myositis-specific autoantibodies and their clinical significance]. AB - The idiopathic inflammatory myopathies polymyositis (PM) and dermatomyositis (DM) have historically been defined using broad clinical and pathological criteria. These conditions affect both adults and children with clinical features including muscle weakness, skin disease, internal organ involvement, and an association with cancer in adults. Using a clinical-serological approach, PM and DM can be defined into more homogeneous subsets. In recent years, myositis-specific autoantibodies (MSAs) have been better characterized and include autoantibodies to the signal-recognition particle and aminoacyl tRNA-synthetase enzymes. In addition, clinically significant novel autoantibodies -anti-p155/p140, anti-CADM 140, and others- have been described in the disease spectrum. MSAs are directed against cytoplasmic or nuclear components involved in key regulatory intracellular processes including protein synthesis, translocation, and transcription. The striking association between unique serological profiles and distinct clinical phenotypes suggests that target autoantigens may play a role in disease induction and propagation. This review reports recent progress in myositis-specific autoantigens, particularly their clinical significance. PMID- 22068473 TI - [Inclusion body myositis]. AB - Sporadic inclusion body myositis (sIBM) is an intractable and progressive skeletal muscle disease of unknown cause that has no curative treatment. Its prevalence varies among countries and ethnic groups. The clinical course is slow and chronic worsening. Diagnosis of sIBM is usually made 5 years after onset. Muscle weakness and atrophy in the quadriceps, wrist flexor, and finger flexors are the typical neurological findings of sIBM. Dysphagia and asymmetric weakness are often found as well. Serum creatine kinase is usually below 2,000 IU/L. Muscle biopsy typically reveals endomysial inflammation, invasion of mononuclear cells into non-necrotic fibers, and rimmed vacuoles, suggesting that inflammation and degeneration are coexist in the pathomechanism. The etiology of sIBM is still unknown; however, genetic factors, aging, lifestyle, and environmental factors may be involved. Recent studies have implicated amyloid beta accumulation, defects of proteolysis, and immune system abnormalities in the pathomechanism of sIBM. sIBM is generally refractory to current therapy, such as steroids or immunosuppressants. Recently, alemtuzumab, which targets T cells, has resulted in improvement in quantitative muscle strength testing. New strategies to induce proteolysis and autophagy, accelerate muscle regeneration, inhibit myostatin, and modulate inflammatory cells are promising. Elucidation of the pathomechanism of sIBM is the key to developing effective therapies. PMID- 22068474 TI - [Management of myocardial damage in muscular dystrophy]. AB - Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future. PMID- 22068475 TI - [Respiratory management in muscular dystrophies]. AB - Respiratory failure is a major contributor to immobility and mortality in progressive muscular dystrophies. The severity of pulmonary impairment and the stage at which it develops differ according to the type of muscular dystrophy. Appropriate respiratory management for each type should be considered. In Duchenne muscular dystrophy (DMD), respiratory impairment manifests in the late teens, and assisted mechanical ventilation is administered. Noninvasive positive pressure ventilation (NIPPV) has increased the median survival of patients with DMD by 10 year and improved quality of life. In myotonic dystrophy (MyD), the causes of respiratory failure can involve both the central and the peripheral nervous systems in addition to respiratory muscles. Nocturnal desaturation is more severe in MyD than in other muscular dystrophies with similar degrees of respiratory muscle weakness. Cognitive impairment should be taken into account in the management of MyD patients. NIPPV does not appear to improve survival of MyD. Guidelines for DMD have been published. Respiratory function should be assessed serially by measuring forced vital capacity, oxyhemoglobin saturation, peak cough flow, and end-tidal CO2 level. A respiratory action plan should be enacted with increasing disease severity. Therapeutic measures comprise airway clearance, respiratory muscle training, noninvasive nocturnal ventilation, daytime noninvasive ventilation, and continuous invasive ventilation. At the advanced stage of respiratory failure, attention should be paid to complications related to long-term mechanical ventilation, such as pneumothorax and tracheal hemorrhage. Discussing about end-of-life care among the patient, family, and physician is important before mechanical ventilatory support is required. PMID- 22068476 TI - [Treatment for neuromuscular scoliosis in duchenne muscular dystrophy]. AB - Patients with neuromuscular disorders are often complicated by progressive scoliosis. No established treatment for this type of scoliosis has been developed, however. We must pay attention to spinal deformity in patients with Duchenne muscular dystrophy, especially after they lose the ability to walk because spinal deformity frequently develops. Patient with progressive scoliosis should be treated by specialists who can perform scoliosis surgery safely. Surgical treatment for scoliosis has developped, and pedicle screw fixation is one of the most widely accepted methods for the treatment of several types of scoliosis. This method is safe and effective. In Europe and the United States, patients with neuromuscular scoliosis usually undergo surgery at a relatively early stage. We should define surgical indications carefully, considering natural history and complications. In addition, sufficient informed consent from patients and their families is of utmost importance. Most surgeons believe that surgical treatment for spinal deformity in neuromuscular disease improves quality of life and activity of daily living. PMID- 22068477 TI - [Psychological support for patients with muscular dystrophy]. AB - The life expectancy of patients with muscular dystrophy has increased in recent while their challenges of activity of daily living persist. Therefore, psychological support is crucial for patients with muscular dystrophy and their family members and caregivers. We have carried out several studies to explore appropriate psychological support for these patients. Individual counseling was effective to support the mental health of patients with muscular dystrophy; however counseling settings should be changed adapted to the physical conditions of patients. A short-term support group for family members was helpful for sharing information and concerns about child rearing. A case conference including physicians, nurses, caseworkers and clinical psychologists was held concerning a decreased patient. Combined case conferences with medical staff reduce psychological stress for staff and prevent from burnout syndrome. Research on how to explain the illness to boys with muscular dystrophy started in 2009. Interviews with adult patients revealed that they had wanted to know about their illness while they were young children. Half of their parents had hoped that their children would recognize the diagnosis by seeing friends with muscular dystrophy during hospitalization. Some of the parents explained the diagnosis to their children directly during childhood, hoping to battle the illness together. In 2010, we studied the attitudes of pediatric neurologists toward explaining the muscular dystrophy diagnosis to children. Seventy percent of respondents answered that patients should be told about their illness. Many of them desired the opportunity to be trained in appropriate ways to tell children about the diagnosis. PMID- 22068478 TI - [Therapeutic readthrough strategy for suppression of nonsense mutations in duchenne muscular dystrophy]. AB - Effective treatment for Duchenne muscular dystrophy (DMD) is currently unavailable. Readthrough of disease-causing premature termination codons might alleviate the symptoms of genetic diseases caused by nonsense mutations. Several ribosome-binding compounds, including selective antibiotics and synthetic novel small molecules, induce translational readthrough, restoring full-length functional proteins. Here in this innovative therapeutic strategy has been summarized with a focus on DMD. We have previously reported that negamycin restored dystrophin expression with less toxicity than gentamicin in mdx mice. To explore more potent readthrough inducers, we established the transgenic mouse called READ (readthrough evaluation and assessment by dural receptor) for readthrough-specific detection. Using READ mice, we discovered drug candidates, including sterically negamycin-like small molecules and aminoglycoside derivatives. The newly developed small molecules induced dose-dependent readthrough with greater potency than ataluren in vitro and promoted the expression of dystrophin and reduction in serum creatine kinase activity in mdx mice. Moreover, the aminoglycoside derivative restored both dystrophin protein and contractile function of mdx skeletal muscles with appreciably higher readthrough activity and lower toxicity than that of gentamicin. Furthermore, we confirmed the efficacy of a thioglycolate-based depilatory agent to enhance the topical delivery of skin-impermeable drugs, including aminoglycosides. These promising new chemotherapeutic agents with beneficial effects on readthrough action, lower toxicity, and transdermal delivery may have significant value in treating or preventing genetic diseases caused by nonsense mutations. PMID- 22068479 TI - [Hematopoietic prostaglandin D synthase inhibitors for the treatment of duchenne muscular dystrophy]. AB - Duchenne muscular dystrophy (DMD) is a severe X-linked muscle disease, characterized by progressive skeletal muscle atrophy and weakness. DMD is caused by mutations in the dystrophin gene, which encodes for the cytoskeletal protein dystrophin. DMD is one of the most common types of muscular dystrophies, affecting approximately 1 in 3,500 boys. There is no complete cure for this disease. Clinical trials for gene transfer therapy as a treatment for DMD have been performed but mainly in animal models. Hematopoietic prostaglandin (PG) D synthase (H-PGDS) was found to be induced in grouped necrotic muscle fibers of DMD patients and animal models, mdx mice, and DMD dogs. We found an orally active H-PGDS inhibitor (HQL-79) and determined the 3D structure of the inhibitor-human H-PGDS complex by X-ray crystallography. Oral administration of HQL-79 markedly suppressed prostaglandin D2 (PGD2) production, reduced necrotic muscle volume, and improved muscle strength in mdx dystrophic mice. Based on the high-resolution 3D structures of the inhibitor-H-PGDS complex, we designed alternative H-PGDS inhibitors, which were 100- to 3000-times more potent than HQL-79, as assessed by in vitro and in vivo analyses. We used these novel inhibitors for the treatment of DMD dogs and confirmed that oral administration of these inhibitors prevented skeletal muscle atrophy and weakness by decreasing PGD2 production. These results indicate that PGD2, synthesized by H-PGDS, is involved in the expansion of muscle necrosis in DMD. Thus, inhibition of H-PGDS by using inhibitors is a novel therapy for DMD. PMID- 22068480 TI - [Myostatin blockade therapy for muscular atrophy]. AB - Myostatin, a member of the muscle-specific transforming growth factor (TGF)-beta family, negatively regulates skeletal muscle growth. It inhibits muscle stem cell proliferation and differentiation and attenuates adult muscle fiber protein accretion, resulting in decreased skeletal muscle mass. As such, it has been considered a therapeutic target of muscular dystrophy. Notably, administration of a blocking antibody against myostatin ameliorated the pathophysiology of dystrophin-deficient mdx mice. Although a clinical trial of anti-myostatin antibody MYO-029 failed to achieve a significant outcome in patients with muscular dystrophies, various distinct approaches have been taken to establish anti-myostatin therapy, including myostatin decoy receptor ACE-031, small molecule inhibitors against the myostatin receptor, and myostatin short intertering RNA with collagen-derived carrier particles. The clinical application of anti-myostatin therapeutics in treatment of patients with muscular dystrophy needs further evaluation for safety and specification of the target disease types among the various muscular dystrophies. In addition, myostatin inhibition could be effective for muscle-wasting conditions other than muscular dystrophy- for instance, steroid-induced myopathy, mitochondrial myopathy, or sarcopenia in elderly patients. Moreover, considerable evidence shows that myostatin regulates energy metabolism and that its inhibition can significantly attenuate the progression of obesity and diabetes. It may also be applicable for the prevention of metabolic syndrome. Thus, safe and potent anti-myostatin therapy will have a wide variety of applications in modern medicine. PMID- 22068481 TI - [Infrastructure for new drug development to treat muscular dystrophy: current status of patient registration (remudy)]. AB - Clinical trials for new therapeutic strategies are now being planned for Duchenne and Becker muscular dystrophies (DMD/BMD); however, many challenges exist in the planning and conduction of a clinical trial for rare diseases. The epidemiological data, total number of patients, natural history, and clinical outcome measures are unclear. Adequate numbers of patients are needed to achieve significant results in clinical trials. As solutions to these problems, patient registries are an important infrastructure worldwide, especially in the case of rare diseases such as DMD/BMD. In Europe, TREAT-NMD, a clinical research network for neuromuscular disorders, developeda global database for dystrophinopathy patients. We developed a national registry of Japanese DMD/BMD patients in collaboration with TREAT-NMD. The database includes clinical and molecular genetic data as well as all required items for the TREAT-NMD global patient registry. As of July 2011, 750 patients were registered in the database. The purpose of this registry is the effective recruitment of eligible patients for clinical trials, and it may also provide timely information to individual patients about upcoming trials. This registry data also provides more detailed knowledge about natural history, epidemiology, and clinical care. In recent years, drug development has become dramatically globalized, and global clinical trials (GCTs) are being conducted in Japan. It is appropriate, particularly with regard to orphan diseases, to include Japanese patients in GCTs to increase evidence for evaluation, because such large-scale trials would be difficult to conduct solely within Japan. GCTs enable the synchronization of clinical drug development in Japan with that in Western countries, minimizing drug approval delays. PMID- 22068482 TI - [Translation and linguistic validation of the Japanese version of the wearing-off questionnaires(WOQ-19 and WOQ-9)]. AB - Levodopa remains the most effective drug for the treatment of Parkinson disease (PD). Long-term levodopa treatment of PD is associated with the development of motor complications, the first of which to occur is the wearing-off phenomenon. In routine clinical practice, poor patient education, communication difficulties, and lack of awareness often hamper detection of the wearing-off phenomenon. Failure to recognize wearing-off may lead to incorrect therapeutic dicision making and/or decline in the patient's quality of life. In order to develop a Japanese version of the 19-symptom and 9-symptom Wearing-off Questionnaires (WOQ 19 and WOQ-9), a linguistic validation was performed to validate the translated version according to the internationally recognized procedure. Forward translation was made independently by 2 Japanese translators with medical knowledge. The Japanese translations were consolidated and revised by the authors into the Japanese draft version. The Japanese draft version was modified into the Japanese final draft by reference to the results of PD patients' surveys. The Japanese final draft was back-translated into English by 2 native translators, and negotiated with the original developers. We thus developed a linguistically validated Japanese version of the WOQ-19 and the WOQ-9. (Received: February 3, 2011, Accepted: March 29, 2011). PMID- 22068483 TI - [Neuroimaging Findings of a 29-year-old woman with 22q11.2 deletion presenting with cognitive deterioration]. PMID- 22068484 TI - Genetic diversity and population structure of Escherichia coli from neighboring small-scale dairy farms. AB - The genetic diversity and population structure of Escherichia coli isolates from small-scale dairy farms were used to assess the ability of E. coli to spread within the farm environment and between neighboring farms. A total of 164 E. coli isolates were obtained from bovine feces, bedding, cow teats and milk from 6 small-scale dairy farms. Ward's clustering grouped the isolates into 54 different random amplified polymorphic DNA (RAPD) types at 95% similarity, regardless of either the sample type or the farm of isolation. This suggests that RAPD types are shared between bovine feces, bedding, cow teats, and milk. In addition, transmission of RAPD types between the studied farms was suggested by the Ward grouping pattern of the isolates, Nei's and AMOVA population analyses, and genetic landscape shape analysis. For the first time, the latter analytical tool was used to assess the ability of E. coli to disseminate between small-scale dairy farms within the same producing region. Although a number of dispersal mechanisms could exist between farms, the genetic landscape shape analysis associated the flow of E. coli RAPD types with the movement of forage and milking staff between farms. This study will aid in planning disease prevention strategies and optimizing husbandry practices. PMID- 22068485 TI - Carnobacterium maltaromaticum infections in feral Oncorhynchus spp. (Family Salmonidae) in Michigan. AB - Members of the genus Oncorhynchus were introduced from the Pacific Northwest to the Laurentian Great Lakes basin and now constitute one of its most commercially and ecologically valuable fisheries. Recently, infections by a group of Gram positive atypical lactobacilli belonging to the genus Carnobacterium have been detected in feral and captive Oncorhynchus spp. broodstock, some of which were associated with mortalities. Out of 1564 rainbow and steelhead trout (O. mykiss), coho salmon (O. kisutch), and Chinook salmon (O. tshawytscha) that were bacteriologically examined, 57 Carnobacterium spp. isolates were recovered from the kidneys, spleen, swimbladder, and/or external ulcerations of 51 infected fish. Phenotypic and biochemical characterization, as well as partial 16S rDNA sequencing and phylogenetic analyses of 30 representative isolates identified 29 as Carnobacterium maltaromaticum and 1 as C. divergens, though some phenotypic and genotypic heterogeneity was observed. Infections with C. maltaromaticum were associated with signitures typical of pseudokidney disease, but on occasion were also observed in fish displaying the gross and histopathological changes characteristic of nephrocalcinosis. While C. maltaromaticum infections were found to be widespread in both feral and farmed spawning populations of Oncorhynchus spp. residing within the Great Lakes basin, infection prevalence varied significantly according to fish species and strain, gender, and across time, but not by sampling location according to logistic regression analysis. The findings of this study further underscore the presence of phenotypic variations among Carnobacterium maltaromaticum strains that necessitate genotypic analysis to achieve definitive identification. PMID- 22068486 TI - Ecological development and genetic diversity of Microcystis aeruginosa from artificial reservoir in Russia. AB - Microcystis aeruginosa is a well-known Cyanobacterium responsible for the formation of toxic water blooms around the world. Shallow, warm, and eutrophic reservoirs provide the most favourable conditions for M. aeruginosa development. Numerous studies have been devoted to this species, but there still is a necessity to develop additional approaches for the monitoring of cyanobacteria in reservoirs. In this study, M. aeruginosa in the water column of a hypereutrophic Siberian reservoir was investigated by fluorescence, light, and electron microscopy as well as genetic analysis using a mcyE marker. Here, we demonstrate the genetic diversity and features of the fluorescence spectra for different ecotypes of this species. We suggest that a fluorescence approach can be used to identify M. aeruginosa in a natural environment in order to increase the effectiveness of ecological monitoring and water quality evaluation. PMID- 22068487 TI - Safety evaluation in vitro of Enterococcus durans from Tibetan traditional fermented yak milk. AB - Despite its ubiquity in fermented dairy products, the safety of lactic acid enterococcal bacteria remains controversial. In this study, five Enterococcus durans strains - A1, A2, B1, B2, and C1 - were isolated from traditional fermented yak milk from Tibet. To evaluate the strains' safety, biogenic amine production, antibiotic resistance and presence of known virulence determinants were investigated. Strain A1 can produce biogenic amines for histamine, spermine, and spermidine (mean values: 8.64, 8.31, and 0.30 mg/L, respectively). Polymerase chain reaction amplification for Strain A1 found genes involved in expression of gelatinase (gleE), cytolysin (cylA, cylB, and cylM), sex pheromones (ccf and cpd) and cell wall adhesion (efaA). Strain A2 showed sensitivity or intermediate resistance to all tested antibiotics, and no virulence determinants except gelE and ccf, but did produce tyramine at a relatively high level (912.02 mg/L). Both strains B1 and B2 could produce histamine (10.43 and 10.56 mg/L, respectively), and showed vancomycin resistance; B1 also produced tyramine (504.02 mg/L). Strain C1 could produce all five biogenic amines tested in the study -putrescine, histamine, tyramine, spermine, and spermidine; concentrations were 6.51, 9.59, 205.85, 5.55, and 5.39 mg/L, respectively. All E. durans strains found in Tibetan traditional fermented yak milk thus offer potential risk. PMID- 22068489 TI - Detection of viruses in farmed rainbow trout (Oncorhynchus mykiss) in Korea by RT LAMP assay. AB - The viral diseases have been the serious problem in salmonid farming, and rainbow trout is not an exception. In this study, routine surveys were conducted for detecting of viruses in farmed rainbow trout (Oncorhynchus mykiss) in Korea during 2009-2010. Head kidneys from individual fish were employed for virus detection by using a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay. Infectious pancreatic necrosis virus (IPNV), infectious hematopoietic necrosis virus (IHNV), and viral hemorrhagic septicemia virus (VHSV) were the target viruses in this study. 53.5% (46/86) were found to be IPNV positive, while IHNV and VHSV showed RT-LAMP negative during examination for 2 years. Ten IPNV-positive samples were randomly selected for viral isolation and the cells showing CPEs were subjected to RT-LAMP, RT-PCR, and direct sequencing. Phylogenetic analysis showed that the rainbow trout isolate has high similarity homologies with the VR-299 strain, as previously described. PMID- 22068488 TI - Comparative approach to capture bacterial diversity of coastal waters. AB - Despite the revolutionary advancements in DNA sequencing technology and cultivation techniques, few studies have been done to directly compare these methods. In this study, a 16S rRNA gene-based, integrative approach combining culture-independent techniques with culture-dependent methods was taken to investigate the bacterial community structure of coastal seawater collected from the Yellow Sea, Korea. For culture-independent studies, we used the latest model pyrosequencer, Roche/454 Genome Sequencer FLX Titanium. Pyrosequencing captured a total of 52 phyla including 27 candidate divisions from the water column, whereas the traditional cloning approach captured only 15 phyla including 2 candidate divisions. In addition, of 878 genera retrieved, 92.1 % of the sequences were unique to pyrosequencing. For culture-dependent analysis, plate culturing, plate washing, enrichment, and high-throughput culturing (HTC) methods were applied. Phylogenetic analysis showed that the plate-washing clones formed a cluster devoid of any previously cultured representatives within the family Rhodobacteraceae. One HTC isolate (SF293) fell into the OM182 clade, which was not recovered by other culturing methods described here. By directly comparing the sequences obtained from cultures with those from culture-independent work, we found that only 33% of the culture sequences were identical to those from clone libraries and pyrosequences. This study presents a detailed comparison of common molecular and cultivation techniques available in microbial ecology. As different methods yielded different coverage, we suggest choosing the approach after carefully examining the scientific questions being asked. PMID- 22068490 TI - Epidemiological investigation of eaeA-positive Escherichia coli and Escherichia albertii strains isolated from healthy wild birds. AB - Escherichia coli has commonly been associated with diarrheal illness in humans and animals. Recently, E. albertii has been reported to be a potential pathogen of humans and animals and to be carried by wild birds. In the present study, the prevalence and genetic characteristics of intimin-producing E. coli and E. albertii strains were evaluated in wild birds in Korea. Thirty one of 790 Enterobacteriaceae strains from healthy wild birds were positive for the intimin gene (eaeA) and twenty two of the 31 strains were identified as atypical enteropathogenic E. coli (aEPEC) that did not possess both EAF and bfpA genes. A total of nine lactose non-fermenting coliform bacterial strains were identified as E. albertii by PCR and sequence analysis of housekeeping genes. A total of 28 (90.3%) eaeA-positive strains were isolated from waterfowl. Fifteen aEPEC (68.2%) and two E. albertii (22.2%) strains had a beta-intimin subtype and 14 aEPEC strains harboring beta-intimin belonged to phylogenetic group B2. AU eaeA positive E. albertii and 3 aEPEC strains possessed the cytolethal distending toxin gene (cdtB). The eaeA-positive E. coli and E. albertii strains isolated from healthy wild birds need to be recognized as a potential pathogroup that may pose a potential threat to human and animal health. These findings indicate that eaeA-positive E. coli as well as E. albertii can be carried by wild birds, posing a potential threat to human and animal health. PMID- 22068491 TI - Production of cephalosporin C using crude glycerol in fed-batch culture of Acremonium chrysogenum M35. AB - In this study, cephalosporin C production by Acremonium chrysogenum M35 cultured with crude glycerol instead of rice oil and methionine was investigated. The addition of crude glycerol increased cephalosporin C production by 6-fold in shake-flask culture, and also the amount of cysteine. In fed-batch culture without methionine, crude glycerol resulted only in overall improvement in cephalosporin C production (about 700%). In addition, A. chrysogenum M35 became highly differentiated in fed-batch culture with crude glycerol, compared with the differentiation in batch culture. The results presented here suggest that crude glycerol can replace methionine and plant oil as cysteine and carbon sources during cephalosporin C production by A. chrysogenum M35. PMID- 22068492 TI - Deciphering the biodiversity of Listeria monocytogenes lineage III strains by polyphasic approaches. AB - Listeria monocytogenes is a foodborne pathogen of humans and animals. The majority of human listeriosis cases are caused by strains of lineages I and II, while lineage III strains are rare and seldom implicated in human listeriosis. We revealed by 16S rRNA sequencing the special evolutionary status of L. monocytogenes lineage III, which falls between lineages I and II strains of L. monocytogenes and the non-pathogenic species L. innocua and L. marthii in the dendrogram. Thirteen lineage III strains were then characterized by polyphasic approaches. Biochemical reactions demonstrated 8 biotypes, internalin profiling identified 10 internal-in types clustered in 4 groups, and multilocus sequence typing differentiated 12 sequence types. These typing schemes show that lineage III strains represent the most diverse population of L. monocytogenes, and comprise at least four subpopulations IIIA-1, IIIA-2, HIB, and IIIC. The in vitro and in vivo virulence assessments showed that two lineage IIIA-2 strains had reduced pathogenicity, while the other lineage III strains had comparable virulence to lineages I and II. The HIB strains are phylogenetically distinct from other sub-populations, providing additional evidence that this sublineage represents a novel lineage. The two biochemical reactions L-rhamnose and L lactate alkalinization, and 10 internalins were identified as potential markers for lineage III subpopulations. This study provides new insights into the biodiversity and population structure of lineage III strains, which are important for understanding the evolution of the L. mono-cytogenes-L. innocua clade. PMID- 22068493 TI - A genome-wide identification of genes potentially associated with host specificity of Brucella species. AB - Brucella species are facultative intracellular pathogenic alpha-Proteobacteria that can cause brucellosis in humans and domestic animals. The clinical and veterinary importance of the bacteria has led to well established studies on the molecular mechanisms of Brucella infection of host organisms. However, to date, no genome-wide study has scanned for genes related to the host specificity of Brucella spp. The majority of bacterial genes related to specific environmental adaptations such as host specificity are well-known to have evolved under positive selection pressure. We thus detected signals of positive selection for individual orthologous genes among Brucella genomes and identified genes related to host specificity. We first determined orthologous sets from seven completely sequenced Brucella genomes using the Reciprocal Best Hits (RBH). A maximum likelihood analysis based on the branch-site test was accomplished to examine the presence of positive selection signals, which was subsequently confirmed by phylogenetic analysis. Consequently, 12 out of 2,033 orthologous genes were positively selected by specific Brucella lineages, each of which belongs to a particular animal host. Extensive literature reviews revealed that half of these computationally identified genes are indeed involved in Brucella host specificity. We expect that this genome-wide approach based on positive selection may be reliably used to screen for genes related to environmental adaptation of a particular species and that it will provide a set of appropriate candidate genes. PMID- 22068494 TI - Bacillus kyonggiensis sp. nov., isolated from soil of a lettuce field. AB - A Gram-positive, rod-shaped, motile, endospore-forming bacterial strain, designated NB22(T), was isolated from soil of a lettuce field in Kyonggi province, South Korea, and was characterized by using a polyphasic taxonomic approach. This novel isolate grew optimally at 30-37 degrees C and pH 8-9. It grew in the presence of 0-4% NaCl (optimum, 1-2%). Comparative 16S rRNA gene sequence analysis showed that strain NB22(T) was closely related to members of the genus Bacillus and fell within a coherent cluster comprising B. siralis 171544(T) (98.1%) and B. korlensis ZLC-26(T) (97.3%). The levels of 16S rRNA gene sequence similarity with respect to other Bacillus species with validly published names were less than 96.4%. Strain NB22(T) had a genomic DNA G+C content of 36.3 mol% and the predominant respiratory quinone was MK-7. The peptidoglycan contained meso-diaminopimelic acid. The major cellular fatty acids were iso C(15:0), anteiso-C(15:0), C(14:0), and C(16:0). These chemotaxonomic results supported the affiliation of strain NB22(T) to the genus Bacillus, and the low DNA-DNA relatedness values and distinguishing phenotypic characteristics allowed genotypic and phenotypic differentiation of strain NB22(T) from recognized Bacillus species. On the basis of the evidence presented, strain NB22(T) is considered to represent a novel species of the genus Bacillus, for which the name Bacillus kyonggiensis sp. nov. is proposed. The type strain is NB22(T) (=KEMB 5401-267(T) =JCM 17569(T)). PMID- 22068495 TI - Use of rpoB sequences and rep-PCR for phylogenetic study of Anoxybacillus species. AB - This study was conducted to investigate the applicability of rpoB, which encodes the beta subunit of RNA polymerase, to be used as an alternative to 16S rRNA gene sequence similarity analysis in the thermophilic genus Anoxybacillus. Partial rpoB sequences were generated for the 14 type strains of Anoxybacillus species and 6 other strains of four Anoxybacillus species. The sequences and the phylogenetic tree of rpoB were compared with those obtained from 16S rRNA gene analysis. The rpoB gene was found to provide a better resolution for Anoxybacillus species, with lower interspecies sequence similarities. The rpoB sequence similarity analysis permitted a more accurate discrimination of the species within the Anoxybacillus genus than the more commonly used 16S rRNA gene. Furthermore, rapid and reproducible repetitive extragenic palindromic fingerprinting techniques (REP-, ERIC-, and BOX-PCR) were employed for the specimens of genus Anoxybacillus. Through comparison of the three methods, it was found that the BOX-PCR method generated more informative results than REP-PCR for the studied strains; BOX-PCR profiles were more distinct for the different strains, including a higher number of bands. Rapid and reproducible repetitive extragenic palindromic fingerprinting techniques (rep-PCR) constitute a suitable molecular approach for the validation and maintenance of taxonomy within the Anoxybacillus genus. The results of this study show that rpoB and rep-PCR provide rapid and reliable methods for molecular typing of Anoxybacillus species. PMID- 22068496 TI - Rapid discrimination of potato scab-causing Streptomyces species based on the RNase P RNA gene sequences. AB - Scab disease significantly damages potatoes and other root crops. Some Streptomyces species have been reported as potato-scab pathogens. Identification of the phytopathogenic Streptomyces is mainly done on the basis of the 16S rRNA gene, but use of this gene has some limitations for discriminating these strains because they share high similarities of 16S rRNA gene sequences. We tested the RNase P RNA (rnpB) gene as a taxonomic marker to clarify the relationship among closely related scab-causing Streptomyces strains. The rnpB genes were analyzed for 41 strains including 9 isolates from Jeju, Korea. There were 4 highly variable regions including nucleotide gaps in the rnpB genes. Interspecies similarity of the rnpB gene in tested Streptomyces strains was lower than about 97%, while the intraspecies similarity was higher than about 98%. Phylogenetic analysis demonstrated that the rnpB tree has similar topology to the 16S rRNA gene tree, but produces a more divergent phyletic lineage. These results revealed that the rnpB gene could be used as a powerful taxonomic tool for rapid differentiation of closely related Streptomyces species. In addition, it was also suggested that the variable regions marked as alpha, beta, gamma, and delta in the rnpB gene could be useful markers for the detection of specific Streptomyces species. PMID- 22068497 TI - Biochemical properties and physiological roles of NADP-dependent malic enzyme in Escherichia coli. AB - Malic enzymes catalyze the reversible oxidative decarboxylation of L-malate using NAD(P)(+) as a cofactor. NADP-dependent malic enzyme (MaeB) from Escherichia coli MG1655 was expressed and purified as a fusion protein. The molecular weight of MaeB was about 83 kDa, as determined by SDS-PAGE. The recombinant MaeB showed a maximum activity at pH 7.8 and 46 degrees C. MaeB activity was dependent on the presence of Mn(2+) but was strongly inhibited by Zn(2+). In order to understand the physiological roles, recombinant E. coli strains (icd (NADP)/DeltamaeB and icd (NAD)/DeltamaeB) containing NADP-dependent isocitrate dehydrogenase (IDH), or engineered NAD-dependent IDH with the deletion of the maeB gene, were constructed using homologous recombination. During growth on acetate, icd (NAD)/DeltamaeB grew poorly, having a growth rate only 60% that of the wild-type strain (icd (NADP)). Furthermore, icd (NADP)/DeltamaeB exhibited a 2-fold greater adaptability to acetate than icd (NAD)/DeltamaeB, which may be explained by more NADPH production for biosynthesis in icd (NADP)/DeltamaeB due to its NADP dependent IDH. These results indicated that MaeB was important for NADPH production for bacterial growth on acetate. We also observed that MaeB activity was significantly enhanced (7.83-fold) in icd (NAD), which was about 3-fold higher than that in icd (NADP), when switching from glucose to acetate. The marked increase of MaeB activity was probably induced by the shortage of NADPH in icd (NAD). Evidently, MaeB contributed to the NADPH generation needed for bacterial growth on two carbon compounds. PMID- 22068498 TI - A novel ribonuclease with potent HIV-1 reverse transcriptase inhibitory activity from cultured mushroom Schizophyllum commune. AB - A 20-kDa ribonuclease (RNase) was purified from fresh fruiting bodies of cultured Schizophyllum commune mushrooms. The RNase was not adsorbed on Affi-gel blue gel but adsorbed on DEAE-cellulose and CM-cellulose. It exhibited maximal RNase activity at pH 6.0 and 70 degrees C. It demonstrated the highest ribonucleolytic activity toward poly (U) (379.5 MU/mg), the second highest activity toward poly (C) (244.7 MU/mg), less activity toward poly (A) (167.4 MU/mg), and much weaker activity toward poly (G) (114.5 MU/mg). The RNase inhibited HIV-1 reverse transcriptase with an IC(50) of 65 MUM. No effect on [(3)H-methyl]-thymidine uptake by lymphoma MBL2 cells and leukemia L1210 cells was observed at 100 MUM concentration of the RNase. A comparison of RNases from S. commune and Volvariella volvacea revealed that they demonstrated some similarities in N terminal amino acid sequence, optimum pH and polyhomoribonucleotide specificity. However, some differences in chromatographic behavior and molecular mass were observed. PMID- 22068499 TI - Biochemical properties of an extracellular trehalase from Malbranchea pulchella var. Sulfurea. AB - The thermophilic fungus Malbranchea pulchella var. sulfurea produced good amounts of extracellular trehalase activity when grown for long periods on starch, maltose or glucose as the main carbon source. Studies with young cultures suggested that the main role of the extracellular acid trehalase is utilizing trehalose as a carbon source. The specific activity of the purified enzyme in the presence of manganese (680 U/mg protein) was comparable to that of other thermophilic fungi enzymes, but many times higher than the values reported for trehalases from other microbial sources. The apparent molecular mass of the native enzyme was estimated to be 104 kDa by gel filtration and 52 kDa by SDS PAGE, suggesting that the enzyme was composed by two subunits. The carbohydrate content of the purified enzyme was estimated to be 19 % and the pi was 3.5. The optimum pH and temperature were 5.0-5.5 and 55 degrees C, respectively. The purified enzyme was stimulated by manganese and inhibited by calcium ions, and insensitive to ATP and ADP, and 1 mM silver ions. The apparent K(M) values for trehalose hydrolysis by the purified enzyme in the absence and presence of manganese chloride were 2.70 +/- 0.29 and 2.58 +/- 0.13 mM, respectively. Manganese ions affected only the apparent V(max), increasing the catalytic efficiency value by 9.2-fold. The results reported herein indicate that Malbranchea pulchella produces a trehalase with mixed biochemical properties, different from the conventional acid and neutral enzymes and also from trehalases from other thermophilic fungi. PMID- 22068500 TI - Adaptive stress response to menadione-induced oxidative stress in Saccharomyces cerevisiae KNU5377. AB - The molecular mechanisms involved in the ability of yeast cells to adapt and respond to oxidative stress are of great interest to the pharmaceutical, medical, food, and fermentation industries. In this study, we investigated the time dependent, cellular redox homeostasis ability to adapt to menadione-induced oxidative stress, using biochemical and proteomic approaches in Saccharomyces cerevisiae KNU5377. Time-dependent cell viability was inversely proportional to endogenous amounts of ROS measured by a fluorescence assay with 2',7' dichlorofluorescin diacetate (DCFHDA), and was hypersensitive when cells were exposed to the compound for 60 min. Morphological changes, protein oxidation and lipid peroxidation were also observed. To overcome the unfavorable conditions due to the presence of menadione, yeast cells activated a variety of cell rescue proteins including antioxidant enzymes, molecular chaperones, energy-generating metabolic enzymes, and antioxidant molecules such as trehalose. Thus, these results show that menadione causes ROS generation and high accumulation of cellular ROS levels, which affects cell viability and cell morphology and there is a correlation between resistance to menadione and the high induction of cell rescue proteins after cells enter into this physiological state, which provides a clue about the complex and dynamic stress response in yeast cells. PMID- 22068501 TI - Degradation of endocrine disrupting chemicals by genetic transformants with two lignin degrading enzymes in Phlebia tremellosa. AB - A white rot fungus Phlebia tremellosa produced lignin degrading enzymes, which showed degrading activity against various recalcitrant compounds. However, manganese peroxidase (MnP) activity, one of lignin degrading enzymes, was very low in this fungus under various culture conditions. An expression vector that carried both the laccase and MnP genes was constructed using laccase genomic DNA of P. tremellosa and MnP cDNA from Polyporus brumalis. P. tremellosa was genetically transformed using the expression vector to obtain fungal transformants showing increased laccase and MnP activity. Many transformants showed highly increased laccase and MnP activity at the same time in liquid medium, and three of them were used to degrade endocrine disrupting chemicals. The transformant not only degraded bisphenol A and nonylphenol more rapidly but also removed the estrogenic activities of the chemicals faster than the wild type strain. PMID- 22068502 TI - Functional analysis of SGR4635-induced enhancement of pigmented antibiotic production in Streptomyces lividans. AB - The Gram-positive mycelium-producing bacterium Streptomyces undergoes complex morphological differentiation after autolytic degradation of the vegetative mycelium. Cell-wall breakdown during growth stimulates cell development and secondary metabolite production by Streptomyces. N-acetylglucosamine (GlcNAc) produced by cell-wall lysis acts as a signal molecule, triggering the production of secondary metabolites in S. coelicolor A3(2). Here, we report that introduction of multiple copies of the GlcNAc-internalizing gene (sgr4635, encoding nagE2) of S. griseus activates actinorhodin and undecylprodigiosin production during the late growth of S. lividans in the absence of GlcNAc. Furthermore, the repressor-type transcriptional regulator DasR binds to two operator sites upstream of sgr4635. Our findings indicate that sgr4635 induces DasR-mediated antibiotic production by internalizing the GlcNAc accumulated from cell-wall lysis. PMID- 22068503 TI - Berberine inhibits HEp-2 cell invasion induced by Chlamydophila pneumoniae infection. AB - This study investigated the inhibitory effects of berberine on Chlamydophila (Chlamydia) pneumoniae infection-induced HEp-2 cell invasion and explored the possible mechanisms involved in this process. C. pneumoniae infection resulted in a significant increase in HEp-2 cell invasion when compared with the control cells (P<0.01) in a Matrigel invasion assay. This enhanced cell invasion was strongly suppressed by berberine (50 MUM) (P<0.01). In a cell adhesion assay, the infection-induced HEp-2 cell adhesion to Matrigel was also significantly inhibited by berberine (P<0.01). C. pneumoniae infection was found to promote HEp 2 cell migration remarkably (P<0.01), which was markedly suppressed by berberine (P<0.01) in the cell migration assays. There were no statistically significant differences in the expression of matrix metalloproteinase-1 (MMP-1) and MMP-9 in the infected cells and berberine did not change the expression of MMP-1 and MMP 9. These data suggest that berberine inhibits C. pneumoniae infection-induced HEp 2 cell invasion through suppressing HEp-2 cell adhesion and migration, but not through changing the expression of MMP-1 and MMP-9. PMID- 22068504 TI - Interaction of Acinetobacter baumannii 19606 and 1656-2 with Acanthamoeba castellanii. AB - Acinetobacter baumannii is virtually avirulent for healthy people but maintains a high virulence among critically ill patients or immuno-compromised individuals. The ability of A. baumannii to adhere to cells and persist on surfaces as biofilms could be central to its pathogenicity. In the present study, we compared the virulence of the A. baumannii 1656-2 clinical strain, which is able to form a thick biofilm, with the virulence of the A. baumannii type strain (ATCC 19606(T)). Acanthamoeba castellanii, a single-celled organism, was used as the host model system to study the virulence of A. baumannii. Compared to A. baumannii ATCC 19606(T), A. baumannii 1656-2 exhibited a higher ability to adhere and invade A. castellanii cells and had a higher killing rate of A. castellanii cells. Furthermore, co-incubation of the amoeba cells and the cell-free supernatant of A. baumannii resulted in the cell death of the amoebae. Heat inactivation or proteinase K treatment of the supernatant did not eliminate its cytotoxicity, suggesting heat stable non-protein factors are responsible for its cytotoxicity to A. castellanii cells. In conclusion, this study for the first time has revealed the capacity of the A. baumannii strain and/or its metabolic products to induce cytotoxicity in A. castellanii cells. PMID- 22068505 TI - Bacteria-based in vivo peptide library screening using biopanning approach. AB - Traditionally, library screening has been performed to identify biologically active agents including small molecules or peptides that inhibit target proteins or molecules with therapeutic interests. Due to its chemical nature, library screening is usually performed under in vitro environments using purified proteins and molecules. However, active agents identified from in vitro screenings often fail to exhibit biological activities in cells. To overcome this inherent limitation, we have developed an in vivo peptide library screening system that allows for the identification of dissociative inhibitors of protein interactions of interest. The screening is based on the reconstitution of the cI repressor from bacteriophage lambda with high-density expression peptide library and is entirely performed in bacteria cells. Furthermore, to enhance the efficacy and sensitivity of the screening, a multiple-round biopanning approach was employed for amplification and enrichment of positive peptides. Overall, this in vivo screening should provide a fast and efficient tool for identification of biologically active peptide molecules against target protein assembly. PMID- 22068506 TI - Microbacterium suwonense sp. nov., isolated from cow dung. AB - An actinomycete strain, designated M1T8B9(T), was isolated from cow dung in Suwon, Republic of Korea. The isolate was a Gram-positive, nonmotile, and non spore-forming bacterium. Phylogenetic evaluation based on 16S rRNA gene sequence similarity showed that this isolate belongs to the genus Microbacterium, with its closest neighbors being Microbacterium soli DCY17(T) (98.2%) and Microbacterium esteraromaticum DSM 8609(T) (98.0%). The polar lipid pattern consisted of diphosphatidylglycerol, phosphatidylglycerol, and one unknown glycolipid. Strain M1T8B9(T) contained the major fatty acids C(15:0) anteiso, C(16:0) iso, C (17:0) anteiso, and C(15:0) iso, and the cell-wall peptidoglycan was of type B2beta. According to DNA-DNA hybridization studies, strain M1T8B9(T) showed 42% and 26% relatedness with M. soli DCY17(T) and M. esteraromaticum DSM 8609(T), respectively. On the basis of the data presented, strain M1T8B9(T) is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium suwonense sp. nov. is proposed. The type strain is M1T8B9(T) (=KACC 14058(T) =NBRC 106310(T)). PMID- 22068507 TI - Pigmentiphaga soli sp. nov., a bacterium isolated from soil. AB - Strain BS12(T), a Gram-negative motile bacterium, was isolated from soil in South Korea and characterized to determine its taxonomic position. Phylogenetic analyses based on the 16S rRNA gene sequence revealed that the strain belonged to the family Alcaligenaceae in the class Betaproteobacteria. The highest degree of sequence similarities of strain BS12(T) were found with Pigmentiphaga litoralis JSM 061001(T) (98.3%), Pigmentiphaga daeguensis K110(T) (98.2%), and Pigmentiphaga kullae K24(T) (98.1%). Chemotaxonomic data revealed that strain BS12(T) possessed ubiquinone-8, which is common in the family Alcaligenaceae, and the predominant fatty acids were C(16:0), C(17:0) cyclo, summed feature 3 (C(16:1) omega6c/omega7c), and summed feature 8 (C(18:1) omega6c/omega7c). The major polar lipids of strain BS12(T) were phosphatidylethanolamine and phosphatidylglycerol. Based on these data, BS12(T) (=KCTC 23577(T) =JCM 17666(T) =KEMB 9004-082(T)) should be classified as a type strain of a novel species, for which the name Pigmentiphaga soli sp. nov. is proposed. PMID- 22068508 TI - Sawadaea koelreuteriae comb, nov., a powdery mildew of Koelreuteria paniculata. AB - A powdery mildew parasitizing Koelreuteria spp. was first described under the name Uncinula koelreuteriae Miyake and later transferred to the genus Typhulochaeta. Based on morphological and molecular data of several herbarium specimens collected from Korea, the generic placement of Typhulochaeta is discussed and T. koelreuteriae is combined in the genus Sawadaea. Redescription and epitypification of this species is provided hereby. PMID- 22068510 TI - Big ideas and grand challenges. PMID- 22068509 TI - Psychosocial care in cancer. AB - Psychosocial care for cancer patients historically has been overlooked as an aspect of quality clinical care. However, several organizations have recently made strong recommendations for inclusion of psychosocial care across the continuum of treatment, from diagnosis, through treatment, into survivorship, and in the palliative stages of care. The evidence base for screening, diagnosis, and effective treatment of psychosocial issues in the context of cancer care is growing. Recent highly relevant research covering major topics in psycho oncology, including distress, delivery of care, psychoneuroimmunology, and cognitive deficits related to cancer, is reviewed in this article. PMID- 22068511 TI - America Invents Act receives cautious welcome. PMID- 22068512 TI - Larger companies dominate cancer companion diagnostic approvals. PMID- 22068516 TI - European ruling raises specter of mandatory GM pollen tests on honey. PMID- 22068520 TI - Industry leaders cite barriers to sequencing in trials. PMID- 22068523 TI - Hemophilia market awaits next-generation therapies. PMID- 22068524 TI - The R&D partnership universe. PMID- 22068525 TI - Biotech plummets in 3Q11. PMID- 22068526 TI - Hepatitis C: move over interferon. PMID- 22068527 TI - A label we don't need. PMID- 22068528 TI - Harnessing cloud computing with Galaxy Cloud. PMID- 22068529 TI - Going viral. PMID- 22068530 TI - Theory of knowledge and biotech patents: worlds apart? PMID- 22068532 TI - Interrogating the kinome. PMID- 22068533 TI - Primate genomes for biomedicine. PMID- 22068534 TI - Road test for genetically modified mosquitoes. PMID- 22068540 TI - How to apply de Bruijn graphs to genome assembly. PMID- 22068541 TI - Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus. AB - Infection with hepatitis C virus (HCV) is a major medical problem with over 170 million people infected worldwide. Substantial morbidity and mortality are associated with hepatic manifestations (cirrhosis and hepatocellular carcinoma), which develop with increasing frequency in people infected with HCV for more than 20 years. Less well known is the burden of HCV disease associated with extrahepatic manifestations (diabetes, B-cell proliferative disorders, depression, cognitive disorders, arthritis and Sjogren's syndrome). For patients infected with genotype 1 HCV, treatment with polyethylene glycol decorated interferon (peginterferon) alpha and ribavirin (PR) is associated with a low (40 50%) success rate, substantial treatment-limiting side effects and a long (48 week) duration of treatment. In the past 15 years, major scientific advances have enabled the development of new classes of HCV therapy, the direct-acting antiviral agents, also known as specifically targeted antiviral therapy for hepatitis C (STAT-C). In combination with PR, the HCV NS3-4A protease inhibitor telaprevir has recently been approved for treatment of genotype 1 chronic HCV in the United States, Canada, European Union and Japan. Compared with PR, telaprevir combination therapy offers significantly improved viral cure rates and the possibility of shortened treatment duration for diverse patient populations. Developers of innovative drugs have to blaze a new path with few validated sign posts to guide the way. Indeed, telaprevir's development was once put on hold because of its performance in a standard IC(50) assay. Data from new hypotheses and novel experiments were required to justify further investment and reduce risk that the drug might fail in the clinic. In addition, the poor drug-like properties of telaprevir were a formidable hurdle, which the manufacturing and formulation teams had to overcome to make the drug. Finally, novel clinical trial designs were developed to improve efficacy and shorten treatment in parallel instead of sequentially. Lessons learned from the development of telaprevir suggest that makers of innovative medicines cannot rely solely on traditional drug discovery metrics, but must develop innovative, scientifically guided pathways for success. PMID- 22068542 TI - Third-quarter biotech job picture. PMID- 22068545 TI - Thrombophilic mutations and susceptibility to preeclampsia in Western Iran. AB - The aim of the present study was to investigate the frequency and the possible association between thrombophilic mutations of factor V Leiden (FVL) and prothrombin G20210A with preeclampsia among Kurdish population of Western Iran. We studied 198 women with preeclampsia including 128 women with mild and 70 women with severe forms and 101 healthy pregnant women with uncomplicated pregnancy. Among cases there were 23 women with early onset preeclampsia and 175 cases with late-onset preeclampsia. The sample was genotyped by polymerase chain reaction restriction fragment-length polymorphism using Mnl I and Hind III for FVL and prothrombin G20210A, respectively. The frequency of heterozygous FVL mutation was 7.6% among all preeclamptic women (8.6% in mild and 5.7% in severe preeclamptic women) and 7.9% in controls (P > 0.05). However, the prevalence of heterozygous FVL were 10.5 and 3.9% among severe preeclamptic women with early onset and late onset preeclampsia, respectively (P > 0.05). The prevalence of prothrombin G20210A were 1.6, 2.9, and 3% among women with mild preeclamsia, severe preeclampsia and controls, respectively (P > 0.05). The level of serum triglycerides (TG) was significantly higher among women with preeclampsia compared to healthy pregnant women that was not associated with the two thrombophilic mutations. Our results indicate that neither FVL nor prothrombin G20210A could be a risk factor for preeclampsia in our population. However, high prevalence of FVL in preeclamptic women with early onset compared to those with late-onset preeclampsia may suggest a role for this mutation in predisposition to early onset preeclampsia that need to be confirmed with larger sample size. PMID- 22068546 TI - Femtosecond lasers for mass spectrometry: proposed application to catalytic hydrogenation of butadiene. AB - Mass spectra from the interaction of intense, femtosecond laser pulses with 1,3 butadiene, 1-butene, and n-butane have been obtained. The proportion of the fragment ions produced as a function of intensity, pulse length, and wavelength was investigated. Potential mass spectrometry applications, for example in the analysis of catalytic reaction products, are discussed. PMID- 22068547 TI - 3,4'-Linked bis(piperidines) related to the haliclonacyclamine class of marine alkaloids: synthesis using crossed-aldol chemistry and preliminary biological evaluations. AB - Compounds 2-5, incorporating various elements of the 3,4'-bis(piperidine) core associated with the sponge-derived alkaloid haliclonacyclamine A (HA, 1), have been prepared through, inter alia, aldol-type reactions of N-substituted piperidin-4-ones and certain derivatives. Screening of these compounds in various assays, including an ecological one, reveals that compound 5 exhibits allelochemical properties similar to those associated with HA itself. PMID- 22068548 TI - Low serum testosterone levels are predictive of prostate cancer. AB - PURPOSE: Although hormones play fundamental roles in prostate growth, their clinical significance is not completely clear. Aims of present study were to assess whether testosterone and serum sex hormone levels are predictors of benign prostatic hyperplasia (BPH) or prostate cancer (PC) and to verify whether prostate cancer is associated with low testosterone levels, and to test association between testosterone levels and known prognostic factors in prostate cancer. METHODS: In 206 consecutive patients with benign prostatic hyperplasia or prostate cancer testosterone, follicle-stimulating hormone, luteinizing hormone and prolactin levels were tested and correlated with disease. In patients with prostate cancer, hormone levels were also correlated with known prognostic factors. Predictive value was assessed for age, prostate-specific antigen (PSA), PSA ratio, PSA density, prostate volume and serum sex hormone levels using multiple logistic regression analysis and receiver operating characteristic curves. RESULTS: Considering sex hormones, only testosterone levels were significantly lower in patients with prostate cancer than those with BPH; testosterone levels appear to be independent predictor of prostate cancer, enhancing predictive accuracy for BPH and PC. Testosterone levels do not seem to be associated with known clinical prognostic factors. CONCLUSIONS: This study supports experimental findings that testosterone levels are predictor of prostate cancer and that prostate cancer is frequently associated with low testosterone levels. In the diagnostic work-up for prostate cancer, adding testosterone determination to PSA test may improve predictive accuracy. PMID- 22068549 TI - Mast cells cultured from IL-3-treated mice show impaired responses to bacterial antigen stimulation. AB - OBJECTIVE AND DESIGN: This study exploits the biological activity of interleukin (IL)-3 to generate high yields of peritoneal mast cells ex vivo in order to examine pro-inflammatory immune responses in ex-vivo culture. MATERIAL OR SUBJECTS: Mast cells were obtained from the peritoneal cavity of C57BL/6 mice. TREATMENT: Mice were injected intraperitoneally twice per day for 5 days with IL 3 (40-50 MUg/ml) to increase mast cell numbers. METHODS: Histological studies examined mast cell numbers in the peritoneal cavity, intestine, lung, spleen and skeletal muscle. Peritoneal mast cells cultured ex vivo (PCMCs) were stimulated for 24 h with lipopolysaccharide and Bordetella pertussis antigen and secretion of tumour necrosis factor-alpha, IL-6, IL-4, IL-5, IL-10 and interferon-gamma into supernatant was measured by commercial ELISA. Cell surface marker expression of FcepsilonRI, c-kit, OX40L and TLR2 was measured by flow cytometry. Mast cell degranulation was measured using a beta-hexosaminidase assay. RESULTS: IL-3 treatment increases mast cell numbers in the peritoneal cavity, spleen and muscle but not intestine and lung of C57BL/6 mice. PCMCs generated from IL-3-treated mice exhibit impaired growth, differentiation and responses to activation as measured by decreased cytokine secretion and cell surface marker expression. CONCLUSION: Mast cells cultured from IL-3-treated mice show impaired responses. PMID- 22068550 TI - Diabetes and incident depression: Is the association mediated or modified by sociodemographic factors or co-morbidities? A systematic review. AB - OBJECTIVE: Diabetic patients suffer more frequently from depression. Aim was to evaluate sociodemographic parameters and co-morbidities and late complications as potential modifying factors in the occurrence of depression in diabetic individuals. RESEARCH DESIGN AND METHODS: We performed a systematic review, based on established meta-analyses and additional original publications in 2005-2009 in Medline and PsycINFO. We included articles focusing on longitudinal studies which evaluated the appearance of depression in diabetic and non diabetic individuals and further analyzed interactions or separate additional influences of potential modifying factors. RESULTS: 8 eligible studies were identified. 6 studies were population based. Only 3 studies analyzed the interaction between the variables of interest and diabetes on the incidence of depression. Remaining used diverse other methods to control for associated factors. The strongest influence was found for a general measure of co-morbidities but this influence was ambiguous. No significant modifying effect or interaction was found for sociodemographic factors. CONCLUSION: There seems to be a clear need for more research concerning mediating and modifying factors or a more stringent presentation of results in order to identify groups at risk or to identify treatment strategies. PMID- 22068551 TI - Determining the waist circumference cut off which best predicts the metabolic syndrome components in urban Africans: the SABPA study. AB - Various studies have shown that the relationship between waist circumference (WC) and abdominal obesity is age, gender as well as ethnicity-dependent. WC criteria for Sub Saharan Africans have not been defined by the International Diabetes Federation (IDF). The aim was to determine which WC cut off best predicted Metabolic Syndrome (MetS) in a group of urban African teachers (80 males and 93 females). We determined sphygmomanometer blood pressure, WC, glucose, high density lipoprotein cholesterol (HdL) and triglyceride (TRIG) values. The males' MetS profile was less favourable as their glucose, TRIG and blood pressure levels were higher than the proposed cut off for MetS. The females could be classified as obese, based on their mean BMI (32.78+/-6.36) and WC (93.48+/-15.68). Receiver operating characteristic (ROC) WC cut offs of 90, 91, 94 and 96 cm for the respective MetS components in males (blood pressure, HdL, glucose and TRIG) were suggested. In the females, cut offs of 92, 98, 94 and 94 cm for TRIG, blood pressure, HdL and glucose respectively, were put forward. Odds ratios revealed that increased blood pressure best predicted ROC WC in both males (OR 9.59; 95% CI 3.14-29.32) and females (OR 3.11; 95% CI 1.30-7.42) irrespective of age. We suggest that the optimal cut off point for the males be set at 90 cm, as opposed to the current 94 cm; whilst the female cut off be set at 98 cm as opposed to the existing cut off of 80 cm. Larger sample groups are recommended to justify our data. PMID- 22068552 TI - Effects of isolated hyperinsulinaemia on sensory function in healthy adults. AB - AIMS: Gastrointestinal symptoms such as pain, bloating, nausea and vomiting are more frequent in pre-diabetic states as well as established diabetes, compared to healthy individuals. The mechanisms behind these symptoms are multi-factorial and complex. Furthermore, the effect of isolated hyperinsulinaemia on visceral and peripheral sensory function is poorly understood. Thus, the current study aimed to evaluate effects of acute hyperinsulinaemia on sensory function in healthy adults. METHODS: The sensitivity to electrical oesophageal and median nerve stimulation was assessed in 15 healthy volunteers together with recording of evoked brain potentials. All subjects were studied both fasting and using a euglycaemic hyperinsulinaemic clamp. RESULTS: There was on average a 15% increased sensitivity to oesophageal electrical stimulation during hyperinsulinaemia compared to fasting state (P<0.05), but the sensation after median nerve stimulation remained stable (P=0.58). No significant changes in latencies and amplitudes of evoked brain potentials were observed after oesophageal or median nerve stimulation (all P>0.05). CONCLUSIONS: This study suggests that acute isolated hyperinsulinaemia increases visceral sensitivity, but does not influence the somatic sensory function. The lack of changes in the evoked brain potentials may indicate that hyperinsulinaemia affects the visceral sensory system at a peripheral level. Our result suggests distinct functions of insulin in the various parts of the nervous system, and yields further clues to the significance of insulin as a satiety signal. PMID- 22068553 TI - Low-level subchronic arsenic exposure from prenatal developmental stages to adult life results in an impaired glucose homeostasis. AB - We evaluated how low-level (3 ppm) subchronic inorganic arsenic (iAs) exposure from prenatal developmental stages until adult life affects glucose homeostasis. Biochemical parameters of glucose and lipid metabolism, pancreatic insulin and glycosylated haemoglobin were determined in 4-month-old female offspring of adult Wistar rats. Pancreatic histology was also performed. Statistical comparisons between control and iAs-treated groups were performed by unpaired two-tailed Student's t-test. Statistical significance was set at p<0.05. We found that iAs treatment resulted in an impaired glucose tolerance test, suggestive of impaired glucose metabolism. This group was found to have hyperglycaemia and high levels of HOMA-IR, glycosylated haemoglobin, cholesterol and pancreatic insulin compared to control rats. However, plasma insulin, triglycerides and high-density lipoprotein cholesterol were not different from control rats. Moreover, beta-cell damage found in iAs-treated rats consisted of cells with a nucleus with dense chromatin and predominance of eosinophilic cytoplasm, as well as changes in the pancreatic vasculature. The current study provided evidence that subchronic iAs exposure at 3 ppm from prenatal developmental stages to adult life resulted in damage to pancreatic beta cells, affected insulin secretion and demonstrated altered glucose homeostasis, thus supporting a causal association between iAs exposure and diabetes. PMID- 22068555 TI - Association of autonomously functioning thyroid nodules with Hashimoto's thyroiditis: study on a large series of patients. AB - OBJECTIVE: Autonomously functioning thyroid nodules (AFTNs) associated with Hashimoto's thyroiditis (HT) are rarely reported. This study evaluates the magnitude of such association, elaborating the clinical and biochemical characteristics of HT and AFTN. MATERIALS AND METHODS: We reviewed the records of our patients with thyroid nodules, including serum TSH, free T4 and T3, Tg-Ab, TPO-Ab, ultrasonography, Tc-99m Sodium Pertechnetate scintigraphy (performed in overt or subclinical hyperthyroid patients). HT patients with coexisting AFTN(s) (group A) were compared with patients with AFTNs alone (group B, n=267). RESULTS: 80 patients (65 women and 15 men; F:M ratio 4.3:1; age 57+/-15 years) had AFTN(s) and coexisting HT. Except 9 patients who were under methimazole, all had suppressed (<0.01 mU/L) or low (<0.4 mU/L) TSH; 17/71 (24%) had increased FT4 and/or FT3. Subclinical hyperthyroidism prevailed over frank hyperthyroidism in group A (76 vs. 24%), but not in group B (56 vs. 44%) ( P=0.005). Group A patients had lower serum FT3 (~0.6 pmol/L or 9%) and FT4 (~0.9 pmol/L or 4%) as compared to group B. The maximum diameter of the AFTN(s) was 8% smaller in group A as compared with group B, thus matching the said difference in FT3. A positive correlation between nodule size and age was found only in group B ( P=0.015). CONCLUSION: Even if difference in the size of nodules between groups A and B does not reach statistical significance, the chronic intrathyroid lymphocytic infiltration of HT may decrease the tendency of the AFTNs to grow and diminish their degree of functioning. PMID- 22068554 TI - Pancreatic autoantibodies, HLA DR and PTPN22 polymorphisms in first degree relatives of patients with type 1 diabetes and multiethnic background. AB - AIM: To evaluate the prevalence of pancreatic auto-antibodies (PAb) as well as its relationship with HLA DR B1 and PTPN22 polymorphisms in first degree relatives (FDR) of Brazilian patients with Type 1 diabetes (T1D) and multiethnic background. METHODS: FDR of patients with T1D were interviewed and blood was sampled for PAb measurement, HLA DRB1 and PTPN22 genotyping. Genotyping was also performed in index cases. RESULTS: In FDR (n=78), 16.7% presented at least one PAb. These individuals had a higher prevalence of HLA DRB1* 03 than others (p=0.03), without differences in PTPN22 genotyping. While the genetic profile was similar in FDR with PAb and their index cases, those without PAb had a lower frequency of HLA DR B1 * 03 than their correspondent patients (p=0.009). CONCLUSION: In this multiethnic population, a significant proportion of FDR of T1D patients had PAb, which was associated with HLA DR B1 * 03 but not with the PTPN22 polymorphism. PMID- 22068556 TI - The promoter variant -803 G>A in the RBP4 gene is not associated with BMI, metabolic parameters or blood pressure in Caucasian children. AB - OBJECTIVE: Studies in adults identified the -803 G>A promoter polymorphism (rs3758539) in the RBP4 gene (RBP4) as a functional variant conferring an increased risk for obesity and type 2 diabetes. METHODS: We genotyped this polymorphism in a cohort of 304 lean and 283 obese children to assess a potential association with early onset obesity and blood pressure and evaluated the effect of this SNP on metabolic parameters in a smaller subset. RESULTS: The allele frequency of -803 G>A was similar in obese compared to lean subjects (0.159 vs. 0.191, P=0.318). We did not detect an association of the variant with adiposity parameters nor with parameters of glucose and lipid metabolism or blood pressure in quantitative analyses. CONCLUSION: Our study revealed that the promoter polymorphism -803 G>A in RBP4 is not associated with BMI, metabolic parameters or blood pressure in Caucasian children. PMID- 22068557 TI - Hypothalamic-pituitary-adrenocortical axis hypersensitivity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome. AB - INTRODUCTION: Molecular mechanisms underlying pathophysiology of polycystic ovary syndrome (PCOS), especially those related to cortisol signaling, are poorly understood. We hypothesized that modulation of glucocorticoid receptor (GR) expression and function, may underlie possible PCOS-related impairment of feedback inhibition of hypothalamic-pituitary-adrenocortical (HPA) axis activity and thus contribute to increased adrenal androgen production in women with PCOS. MATERIALS AND METHODS: 24 normal-weight and 31 obese women with PCOS were compared to 25 normal-weight controls. Fasting blood samples were collected for measurements of serum concentrations of dehydroepiandrosterone sulfate, testosterone, sex hormone-binding globulin, insulin, basal cortisol and cortisol after oral administration of 0.5 mg dexamethasone. Concentrations of GR mRNA, GR protein, mineralocorticoid receptor (MR) protein and heat shock proteins (Hsps), as well as the number of GR per cell (B(max)) and its equilibrium dissociation constant (K(D)) were measured in isolated peripheral blood mononuclear cells. RESULTS: An increase in HPA axis sensitivity to dexamethasone, an elevation of the GR protein concentration, and unaltered receptor functional status were found in both normal-weight and obese women with PCOS vs. healthy controls. Lymphocyte MR, Hsp90 and Hsp70 concentrations, and MR/GR ratio were similar in all groups. Correlation between B(max) and K(D) was weaker in the group of obese women with PCOS than in the other 2 groups. CONCLUSIONS: The results did not confirm the initial hypothesis, but imply that PCOS is associated with increased GR protein concentration and HPA axis sensitivity to dexamethasone. PMID- 22068558 TI - Relationship between plasma aldosterone concentration and soluble cellular adhesion molecules in patients referred to coronary angiography. AB - OBJECTIVE: Evidence is emerging that aldosterone contributes to the development and progression of atherosclerosis and cardiovascular disease. Little is known, however, regarding an association between circulating aldosterone levels and soluble cellular adhesion molecules in humans. METHODS: We investigated the relationship between plasma aldosterone concentration (PAC) and soluble cellular adhesion molecules in a large cohort of patients referred to coronary angiography. After exclusion of patients with ongoing mineralocorticoid receptor blocker use, oral contraceptive or hormone replacement therapy, 1,733 patients (mean age: 62.5+/-10.8 years; 26.4%% women; mean PAC: 101.5+/-93.5 pg/mL) remained eligible for analyses. RESULTS: Pearson correlation analysis as well as age and gender adjusted partial correlation analysis revealed a positive association between PAC and soluble (s) E-, L- and P-selectin levels but not with sICAM-1 and sVCAM-1, respectively. In multivariate adjusted analyses of covariance (ANCOVA) sE- (p=0.026), sL- (p=0.049) and sP-selectin (p<0.001) levels increased steadily from the first (reference) to the third gender-specific tertile of PAC. No significant variation across PAC tertiles was found for sICAM 1 (p=0.767) and sVCAM1 (p=0.425) levels, respectively. Finally, multivariate regression analyses revealed circulating aldosterone as an important predictor for soluble selectin levels. CONCLUSION: Our findings in a large cohort of patients indicate that upregulation of selectins might represent a novel mechanism of aldosterone mediated development and progression of atherosclerosis. In view of aldosterone as a novel cardiovascular risk factor independent of angiotensin II, our findings warrant further interventional studies which should evaluate anti-atherosclerotic effects of aldosterone blocking treatment strategies in humans. PMID- 22068559 TI - Abnormal N-heterocyclic carbene palladium complex: living catalyst for activation of aryl chlorides in Suzuki-Miyaura cross coupling. AB - Palladium complexes bearing abnormal N-heterocyclic carbene were used as catalysts in Suzuki-Miyaura cross coupling of aryl chlorides at 25 degrees C. The catalyst remained active for 10 successive catalytic runs and can activate 4 chlorotoluene at 25 degrees C with 0.01 mol% catalyst loading resulting in a TON of 9500 within 6 h. PMID- 22068562 TI - Multiallelic models of genetic effects and variance decomposition in non equilibrium populations. AB - Quantitative genetics stems from the theoretical models of genetic effects, which are re-parameterizations of the genotypic values into parameters of biological (genetic) relevance. Different formulations of genetic effects are adequate to address different subjects. We thus need to generalize and unify them under a common framework for enabling researchers to easily transform genetic effects between different biological meanings. The Natural and Orthogonal Interactions (NOIA) model of genetic effects has been developed to achieve this aim. Here, we further implement the statistical formulation of NOIA with multiple alleles under Hardy-Weinberg departures (HWD). We show that our developments are straightforwardly connected to the decomposition of the genetic variance and we point out several emergent properties of multiallelic quantitative genetic models, as compared to the biallelic ones. Further, NOIA entails a natural extension of one-locus developments to multiple epistatic loci under linkage equilibrium. Therefore, we present an extension of the orthogonal decomposition of the genetic variance to multiple epistatic, multiallelic loci under HWD. We illustrate this theory with a graphical interpretation and an analysis of published data on the human acid phosphatase (ACP1) polymorphism. PMID- 22068563 TI - The combined effects of Pseudomonas fluorescens and Tuber melanosporum on the quality of Pinus halepensis seedlings. AB - The ecological, economic and social values of the ectomycorrhizal fungi of the black truffle found in the rural Mediterranean are well known. The inoculation of Pinus halepensis seedlings with mycorrhizal fungi and rhizobacteria can improve the morphology and physiology of the seedlings and benefit the regeneration of arid regions and the reintroduction of inocula of mycorrhizal fungi into these areas. Some rhizobacteria can improve the establishment and functioning of ectomycorrhizal symbiosis. In this study, seedlings of P. halepensis were inoculated with the mycorrhizal fungus Tuber melanosporum and the rhizobacteria Pseudomonas fluorescens CECT 844 under non-limiting greenhouse conditions. Five months after inoculation, we analysed the growth, water parameters (osmotic potential at saturation, osmotic potential at turgor loss and modulus of elasticity), concentrations of mycorrhizal colonies, nutrient concentration and nutrient contents (N, P, K, Ca, Mg and Fe) in roots and aerial parts of the seedlings. Subsequently, tests were performed to estimate the root growth potentials. None of the treatments changed the water parameters or growth potentials of the roots. The inoculations improved the growth and nutrient uptake of the seedlings, although the combination of P. fluorescens CECT 844 and T. melanosporum did not generally lead to a significant improvement over the positive effects of a simple inoculation of T. melanosporum; however, the addition of P. fluorescens CECT 844 did double the rate of the mycorrhization of T. melanosporum. These results may be promising for enhancing the cultivation of truffles. PMID- 22068564 TI - The SNM practice guideline for somatostatin receptor scintigraphy 2.0. PMID- 22068565 TI - The excited states and vibronic spectroscopy of diphenyldiacetylene and diphenylvinylacetylene. AB - Laser induced fluorescence (LIF) excitation scans and dispersed fluorescence (DFL) spectra have been recorded for two four-carbon alpha,omega-diphenyl systems, diphenyldiacetylene (DPDA, phi-C=C-C=C-phi) and trans diphenylvinylacetylene (DPVA, phi-CH=CH-C=C-phi) as isolated molecules cooled in a supersonic expansion. While these molecules have similar conjugation length, they exhibit strikingly different vibronic spectroscopy and photophysics. The near-UV LIF excitation spectrum of diphenyldiacetylene has its electronic origin at 32,158 cm(-1), and a strong progression in the C=C stretch (2156 cm(-1)). All transitions are inherently broad, with widths of ~30 cm(-1) fwhm or greater. The S(1) origin DFL spectrum is composed of sharp transitions with Franck-Condon activity mirroring that in the excitation spectrum, and broad emission shifted well to the red ascribable to phosphorescence on the MUs timescale. Using ab initio calculations, it is possible to show that DPDA exists as a single, planar conformer with D(2h) symmetry. In contrast, trans-diphenylvinylacetylene shows intense sharp transitions in both LIF and DFL spectra with an S(0)-S(1) origin of 31,183.2 cm(-1) and long progressions involving the in-plane fundamentals nu(53) (bridge-phenyl bending) and nu(51) (bridge-phenyl stretch). A sharp reduction in fluorescence yield in DPVA occurs within 300 cm(-1) of the S(1) origin. Possible causes for the photophysical processes occurring in the two molecules are discussed. PMID- 22068566 TI - Preparation and characterization of chitosan hybrid membranes containing polyethylacrylate and polybutylacrylate. AB - Chitosan hybrid membranes were prepared in the presence of polyethylacrylate and polybutylacrylate and characterized by measuring stress, strain, Young's modulus, swelling behavior and antibacterial properties against gram-negative and gram positive bacteria using IR spectroscopy and scanning electron microscopy (SEM). The results show that the mechanical properties of the hybrid membranes were enhanced using polybutylacrylate. SEM images showed homogeneity of the prepared membranes. The swelling degree was of the order chitosan > chitosan/polyethylacrylate > chitosan/polybutylacrylate. Antibacterial properties of the hybrid membranes with polybutylacrylate and polyethylacrylate were higher than those of chitosan membranes without any additives. PMID- 22068567 TI - Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells. AB - Although Chinese hamster ovary (CHO) cells, with their unique characteristics, have become a major workhorse for the manufacture of therapeutic recombinant proteins, one of the major challenges in CHO cell line generation (CLG) is how to efficiently identify those rare, high-producing clones among a large population of low- and non-productive clones. It is not unusual that several hundred individual clones need to be screened for the identification of a commercial clonal cell line with acceptable productivity and growth profile making the cell line appropriate for commercial application. This inefficiency makes the process of CLG both time consuming and laborious. Currently, there are two main CHO expression systems, dihydrofolate reductase (DHFR)-based methotrexate (MTX) selection and glutamine synthetase (GS)-based methionine sulfoximine (MSX) selection, that have been in wide industrial use. Since selection of recombinant cell lines in the GS-CHO system is based on the balance between the expression of the GS gene introduced by the expression plasmid and the addition of the GS inhibitor, L-MSX, the expression of GS from the endogenous GS gene in parental CHOK1SV cells will likely interfere with the selection process. To study endogenous GS expression's potential impact on selection efficiency, GS-knockout CHOK1SV cell lines were generated using the zinc finger nuclease (ZFN) technology designed to specifically target the endogenous CHO GS gene. The high efficiency (~2%) of bi-allelic modification on the CHO GS gene supports the unique advantages of the ZFN technology, especially in CHO cells. GS enzyme function disruption was confirmed by the observation of glutamine-dependent growth of all GS-knockout cell lines. Full evaluation of the GS-knockout cell lines in a standard industrial cell culture process was performed. Bulk culture productivity improved two- to three-fold through the use of GS-knockout cells as parent cells. The selection stringency was significantly increased, as indicated by the large reduction of non-producing and low-producing cells after 25 uM L-MSX selection, and resulted in a six-fold efficiency improvement in identifying similar numbers of high-productive cell lines for a given recombinant monoclonal antibody. The potential impact of GS-knockout cells on recombinant protein quality is also discussed. PMID- 22068568 TI - Gracilis transposition for prostato-rectal fistula. PMID- 22068569 TI - Oral non-absorbable antibiotics for colorectal surgery. PMID- 22068570 TI - Reading too much into anal vector volumetric parameters: correspondence for "Anal vector volume analysis: an effective tool in the management of pelvic floor disorders" M. Grande, F. Cadeddu, P. Silveri, P. Ciano, G. M. Attina, I. Selvaggio, G. Milito. Tech Coloproctol (2011) 15:31-37. PMID- 22068571 TI - Training and technical assistance: lessons learned to sustain social norm changes in tobacco control. PMID- 22068573 TI - Technical assistance and tobacco control: a conversation with Dr. Ursula Bauer. Interview. PMID- 22068572 TI - The Tobacco Technical Assistance Consortium: a foundation-university partnership to reduce tobacco use. PMID- 22068574 TI - Building the evaluation capacity of California's local tobacco control programs. AB - Successful evaluation capacity building requires a dynamic balance between responding to local agency needs and ensuring that local staff have appropriate skills to conduct rigorous evaluations. In 2004, the California Tobacco Control Program established the Tobacco Control Evaluation Center (TCEC), based at a public research university, to provide evaluation technical assistance to approximately 100 local agencies implementing tobacco control programs. TCEC has been responsive to local needs, for instance, by answering 512 technical assistance requests in the first 5 years of operation and by tailoring training according to needs assessment results. About 50% of the technical assistance requests were for new data collection instruments (n = 255). TCEC has sought proactively to improve local evaluation skills, most recently in a data analysis and report writing skill building campaign that included a webinar, newsletter, and seven regional training meetings. Preliminary analysis suggests a 20% improvement in scores for the local final evaluation reports as a result of this campaign. It is concluded that evaluation technical assistance can be provided effectively by a university as long as the local context is kept in mind, and a balance of responsive and proactive technical assistance is provided. PMID- 22068575 TI - Applying the performance partnership model to smoking cessation: lessons learned by the smoking cessation leadership center. AB - A wide array of partners can be convened around a single measurable outcome, such as driving down smoking prevalence, through the use of an innovative approach called the performance partnership model. This approach has certain key characteristics that make it different from ordinary coalition building, such as following four steps leading to a baseline, a target, an action plan, and an impact measurement plan. It also employs great speed and focus to keep partners engaged, and it has led to demonstrable progress on smoking cessation nationwide. PMID- 22068576 TI - The use of training and technical assistance to drive and improve performance of California's Tobacco Control Program. AB - The California Department of Public Health, California Tobacco Control Program uses a social norm-change strategy to reduce the uptake and continued use of tobacco products. The statewide media campaign frames the message, community level projects implement advocacy campaigns, and statewide-funded projects build the capacity of community-level projects. The California Tobacco Control Program's technical assistance (TA) system has evolved over time because of changing needs, evaluation findings, and budget considerations. However, TA services continue to strategically align with four statewide policy priorities: to eliminate secondhand smoke exposure, to counter protobacco influences, to reduce the availability of tobacco, and to promote cessation services. TA is the engine powering social change across California by playing a key role in the uptake of a single policy to facilitating the adoption of hundreds of tobacco control policies statewide. The inclusion of expert and peer-to-peer TA models broadly disseminates both evidence-based and tacit community-based knowledge. Comprehensive TA also levels the playing field for organizations and communities to effectively implement policy interventions. Together these approaches accelerate change throughout California communities. PMID- 22068577 TI - Addressing tobacco use in homeless populations: recommendations of an expert panel. AB - A diverse group of panelists met for one day on October 21, 2009, in Washington, DC, for the purpose of addressing the high tobacco use prevalence rates in homeless populations; identifying appropriate policy, cessation practices and models for implementation in this population; and providing targeted recommendations for researchers, homeless service providers, tobacco control advocates, and policy makers. The panel was convened by Break Free Alliance, one of six national networks funded by the Centers for Disease Control and Prevention, Office on Smoking and Health. The panelists worked through a process of problem identification, generation of responses, analysis and prioritization, development of recommendations, and arrival of final decisions reached by consensus. The resulting recommendations for addressing tobacco use in homeless populations focused on tobacco non-use policy implementation, cessation programming, and expansion of partnerships and collaborations between tobacco control advocates and social service providers. The panel also identified unanswered research questions that can serve to develop a framework for future initiatives to reduce tobacco use among homeless persons. The expert panel model serves as one approach for engaging nontraditional partners and building consensus among leaders from a variety of sectors to address tobacco use in special populations. PMID- 22068578 TI - Getting universal primary tobacco use prevention into priority area schools: a media literacy approach. AB - The impact of any prevention intervention depends on its ability to influence health risks and behavior change and the extent to which the target audience has access to and participates in the program. In this article, the authors make the case that media literacy-based tobacco prevention education can be integrated into the middle school curriculum in a way that delivers on both counts. They describe Missouri's successful development and dissemination of the Youth Empowerment in Action! Tobacco Education, Advocacy, and Media curriculum to schools serving populations that are most vulnerable to tobacco-related health disparities. They make three recommendations to support health program developers' efforts to motivate and prepare teachers to implement and sustain universal tobacco prevention education in areas of highest need. PMID- 22068579 TI - Culture change in addictions treatment: a targeted training and technical assistance initiative affects tobacco-related attitudes and beliefs in addiction treatment settings. AB - Targeted training and technical assistance can have a major impact on the attitudes and beliefs of addiction service providers with respect to the treatment of tobacco dependency. Major gains have been made with the general public since the mid-1960s with respect to the reduction of tobacco use behavior and tobacco-related diseases. Tobacco use continues to be a major public health problem, and tobacco control initiatives are significantly affecting public attitudes and norms regarding tobacco use. There is, however, a specific population that has not benefited from these gains and, in fact, has been encouraged to continue smoking rather than make an attempt to quit. Individuals with a substance use disorder and/or mental health disorder have a much higher percentage of tobacco use than the general population, resulting in major health disparities. The addiction treatment and recovery community has lagged behind the general public in addressing tobacco use. New York State's project, "Integrating Tobacco Use Interventions Into Chemical Dependence Services," is a model that demonstrates how innovative regulations, and training and technical assistance developed specifically for addiction service providers, can initiate culture change with respect to tobacco use within addiction treatment settings, resulting in improved treatment outcomes and longer term stable recovery. PMID- 22068580 TI - Developing approaches for evaluating smoke-free policies: a case study of a collaborative response to an emerging technical assistance need. AB - This article describes how several tobacco control organizations identified and responded to an emerging need for technical assistance on how to evaluate smoke free policies. The authors outline the purposes of evaluating smoke-free policies and present examples of evaluation approaches and tools. Examples are provided of how evaluation has been used to advance the adoption, implementation, and defense of smoke-free policies. Opportunities for further research are identified. Finally, the authors review lessons learned and discuss their implications for evaluating policy initiatives addressing other public health issues. PMID- 22068581 TI - Supporting tobacco control: stimulating local newspaper coverage with a technical assistance website for local coalitions. AB - A large and growing literature confirms that well-designed web-based programs can be effective in preventing or treating several chronic diseases. This study examined how the Internet can deliver information and train community activists and specifically tested the effects of web-based technical assistance on local tobacco control coalitions' efforts to use media advocacy to advance their agendas. The authors compared a highly interactive, Enhanced website (intervention) to a noninteractive, Basic text-based website (comparison) in Colorado communities. A total of 24 tobacco control coalitions led by local county health departments and nursing services were enrolled in the project and randomly assigned to use either the intervention or comparison website. A total of 73 local daily and weekly newspapers were identified in the service areas of 23 of the 24 coalitions. A posttest assessment of newspaper coverage was conducted to locate all newspaper articles with tobacco control information published between January 1 and April 9, 2004, the last 3 months of the intervention. Although there was no evidence of a treatment effect on the frequency of newspaper articles on tobacco-related issues, there was, however, evidence that newspapers in counties where the coalition had access to the Enhanced website printed more stories focused on local/regional issues and more anti-tobacco local/regional stories than in the counties where coalitions had access to the Basic website. Coalitions can improve their influence on local media for community tobacco control when high-quality online technical assistance, training, and resources are available to them. PMID- 22068582 TI - Training leaders from priority populations to implement social norm changes in tobacco control: lessons from the LAAMPP Institute. AB - The development of leadership in tobacco control has been crucial in the fight against the number one most preventable cause of death and disease worldwide. Yet today, little scientific evidence exists regarding its actual impact, particularly among priority populations. This article describes the impact of the Leadership and Advocacy Institute to Advance Minnesota's Parity for Priority Populations (LAAMPP Institute), a major tobacco control leadership program for five priority populations: African/African Americans, American Indians, Asian Americans, Chicano/Latinos, and lesbian, gay, bisexual, transgender communities in Minnesota. The LAAMPP Institute, a year-long institute with 17 days of training, focused on the core competencies of advocacy, collaboration, cultural or community competency, facilitation, and tobacco control. A logic model helped to guide and frame the institute's efforts. The LAAMPP Institute has been effective in increasing fellows' capacity to do advocacy, which in turn has led to increased involvement in implementing social norm-change activities. Leadership development can provide a solid foundation for training leaders and a catalyst for mobilizing key advocates and priority population communities toward the implementation and sustainment of social norm or policy changes. PMID- 22068583 TI - Stories from the field. AB - "Stories From the Field" is a series of short profiles of tobacco control programs and their leaders, showcasing promising technical assistance and training models in Louisiana, Puerto Rico, the Cherokee Nation, West Virginia, the Pacific Islands, and the Virgin Islands. The series illuminates key themes of collaboration with diverse stakeholders, elimination of health disparities, building tobacco control coalitions, engaging youth to reduce commercial tobacco use, sustaining tobacco control efforts, and the use of the media to raise public awareness that are highlighted in the Health Promotion Practice Supplement Theme Issue, Training and Technical Assistance: Lessons Learned to Sustain Social Norm Changes in Tobacco Control. Common tobacco control strategies bind the stories together. Local knowledge, coalition building, community involvement, innovative partnerships, and educational outreach are at the core of all of these tobacco control projects. PMID- 22068584 TI - From movement to thought: executive function, embodied cognition, and the cerebellum. AB - This paper posits that the brain evolved for the control of action rather than for the development of cognition per se. We note that the terms commonly used to describe brain-behavior relationships define, and in many ways limit, how we conceptualize and investigate them and may therefore constrain the questions we ask and the utility of the "answers" we generate. Many constructs are so nonspecific and over-inclusive as to be scientifically meaningless. "Executive function" is one such term in common usage. As the construct is increasingly focal in neuroscience research, defining it clearly is critical. We propose a definition that places executive function within a model of continuous sensorimotor interaction with the environment. We posit that control of behavior is the essence of "executive function," and we explore the evolutionary advantage conferred by being able to anticipate and control behavior with both implicit and explicit mechanisms. We focus on the cerebellum's critical role in these control processes. We then hypothesize about the ways in which procedural (skill) learning contributes to the acquisition of declarative (semantic) knowledge. We hypothesize how these systems might interact in the process of grounding knowledge in sensorimotor anticipation, thereby directly linking movement to thought and "embodied cognition." We close with a discussion of ways in which the cerebellum instructs frontal systems how to think ahead by providing anticipatory control mechanisms, and we briefly review this model's potential applications. PMID- 22068585 TI - Dual-energy computed tomography applications in uroradiology. AB - The introduction of dual-energy computed tomography systems (ie, scanners that can simultaneously acquire images at different energies) has significant and unique applications for urologists. Imaging data from these scanners can be used to evaluate composition of urinary calculi and, by "removing" iodine from an image, significantly decrease radiation dose to patients referred for hematuria. Further, the ability to create a virtual noncontrast image obviates the need for repeated scanning in patients with incidentally detected renal and adrenal masses. Finally, the ability to quantify the regional concentration of iodine in a renal neoplasm may provide a method to monitor effectiveness of therapy before size changes become apparent. PMID- 22068586 TI - Molecular and cellular characteristics of ABCA3 mutations associated with diffuse parenchymal lung diseases in children. AB - ABCA3 (ATP-binding cassette subfamily A, member 3) is expressed in the lamellar bodies of alveolar type II cells and is crucial to pulmonary surfactant storage and homeostasis. ABCA3 gene mutations have been associated with neonatal respiratory distress (NRD) and pediatric interstitial lung disease (ILD). The objective of this study was to look for ABCA3 gene mutations in patients with severe NRD and/or ILD. The 30 ABCA3 coding exons were screened in 47 patients with severe NRD and/or ILD. ABCA3 mutations were identified in 10 out of 47 patients, including 2 homozygous, 5 compound heterozygous and 3 heterozygous patients. SP-B and SP-C expression patterns varied across patients. Among patients with ABCA3 mutations, five died shortly after birth and five developed ILD (including one without NRD). Functional studies of p.D253H and p.T1173R mutations revealed that p.D253H and p.T1173R induced abnormal lamellar bodies. Additionally, p.T1173R increased IL-8 secretion in vitro. In conclusion, we identified new ABCA3 mutations in patients with life-threatening NRD and/or ILD. Two mutations associated with ILD acted via different pathophysiological mechanisms despite similar clinical phenotypes. PMID- 22068587 TI - A RANKL G278R mutation causing osteopetrosis identifies a functional amino acid essential for trimer assembly in RANKL and TNF. AB - Receptor activator of nuclear factor-kappaB ligand (RANKL), a trimeric tumor necrosis factor (TNF) superfamily member, is the central mediator of osteoclast formation and bone resorption. Functional mutations in RANKL lead to human autosomal recessive osteopetrosis (ARO), whereas RANKL overexpression has been implicated in the pathogenesis of bone degenerative diseases such as osteoporosis. Following a forward genetics approach using N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we generated a novel mouse model of ARO caused by a new loss-of-function allele of Rankl with a glycine-to-arginine mutation at codon 278 (G278R) at the extracellular inner hydrophobic F beta-strand of RANKL. Mutant mice develop severe osteopetrosis similar to Rankl-deficient mice, whereas exogenous administration of recombinant RANKL restores osteoclast formation in vivo. We show that RANKL(G278R) monomers fail to assemble into homotrimers, are unable to bind and activate the RANK receptor and interact with wild-type RANKL exerting a dominant-negative effect on its trimerization and function in vitro. Since G278 is highly conserved within the TNF superfamily, we identified that a similar substitution in TNF, G122R, also abrogated trimerization, binding to TNF receptor and consequently impaired TNF biological activity. Notably, SPD304, a potent small-molecule inhibitor of TNF trimerization that interacts with G122, also inhibited RANKL activity, suggesting analogous inhibitory mechanisms. Our results provide a new disease model for ARO and identify a functional amino acid in the TNF-like core domain essential for trimer formation both in RANKL and in TNF that could be considered a novel potential target for inhibiting their biological activities. PMID- 22068588 TI - Postnatal neurogenesis generates heterotopias, olfactory micronodules and cortical infiltration following single-cell Tsc1 deletion. AB - Neurological symptoms in tuberous sclerosis complex (TSC) and associated brain lesions are thought to arise from abnormal embryonic neurogenesis due to inherited mutations in Tsc1 or Tsc2. Neurogenesis persists postnatally in the human subventricular zone (SVZ) where slow-growing tumors containing Tsc-mutant cells are generated in TSC patients. However, whether Tsc-mutant neurons from the postnatal SVZ contribute to brain lesions and abnormal circuit remodeling in forebrain structures remain unexplored. Here, we report the formation of olfactory lesions following conditional genetic Tsc1 deletion in the postnatal SVZ using transgenic mice or targeted single-cell electroporation. These lesions include migratory heterotopias and olfactory micronodules containing neurons with a hypertrophic dendritic tree. Most significantly, our data identify migrating glial and neuronal precursors that are re-routed and infiltrate forebrain structures (e.g. cortex) and become glia and neurons. These data show that Tsc1 mutant cells from the neonatal and juvenile SVZ generate brain lesions and structural abnormalities, which would not be visible using conventional non invasive imaging. These findings also raise the hypothesis that micronodules and the persistent infiltration of cells to forebrain structures may contribute to network malfunction leading to progressive neuropsychiatric symptoms in TSC. PMID- 22068590 TI - Modeling the human MTM1 p.R69C mutation in murine Mtm1 results in exon 4 skipping and a less severe myotubular myopathy phenotype. AB - X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin. The Mtm1 knockout (KO) mouse has a severe phenotype and its short lifespan (8 weeks) makes it a challenge to use as a model in the testing of certain preclinical therapeutics. Many MTM patients succumb early in life, but some have a more favorable prognosis. We used human genotype-phenotype correlation data to develop a myotubularin-deficient mouse model with a less severe phenotype than is seen in Mtm1 KO mice. We modeled the human c.205C>T point mutation in Mtm1 exon 4, which is predicted to introduce the p.R69C missense change in myotubularin. Hemizygous male Mtm1 p.R69C mice develop early muscle atrophy prior to the onset of weakness at 2 months. The median survival period is 66 weeks. Histopathology shows small myofibers with centrally placed nuclei. Myotubularin protein is undetectably low because the introduced c.205C>T base change induced exon 4 skipping in most mRNAs, leading to premature termination of myotubularin translation. Some full-length Mtm1 mRNA bearing the mutation is present, which provides enough myotubularin activity to account for the relatively mild phenotype, as Mtm1 KO and Mtm1 p.R69C mice have similar muscle phosphatidylinositol 3-phosphate levels. These data explain the basis for phenotypic variability among human patients with MTM1 p.R69C mutations and establish the Mtm1 p.R69C mouse as a valuable model for the disease, as its less severe phenotype will expand the scope of testable preclinical therapies. PMID- 22068589 TI - Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects. AB - The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/beta-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression. PMID- 22068592 TI - A submicron plasmonic dichroic splitter. AB - Spectral imaging and sensing techniques, new solar cell designs and wavelength division multiplexing in optical communication rely on structures that collect and sort photons by wavelength. The strong push for chip-scale integration of such optical components has necessitated ultracompact, planar structures, and fomented great interest in identifying the smallest possible devices. Consequently, novel micro-ring, photonic crystal and plasmonic solutions have emerged. Meanwhile, the optical coupling of subwavelength plasmonic structures supporting a very limited number of modes has also enabled new functionalities, including Fano resonances and structural electromagnetically-induced transparency. Here we show how two similarly sized subwavelength metal grooves can form an ultracompact submicron plasmonic dichroic splitter. Each groove supports just two electromagnetic modes of opposite symmetry that allows independent control of how a groove collects free-space photons and directs surface plasmon polaritons. These results show how the symmetry of electromagnetic modes can be exploited to build compact optical components. PMID- 22068591 TI - Direct stereoselective alpha-arylation of unmodified enals using an organocatalytic cross-coupling-like reaction. AB - Cross-coupling reactions typically rely on the use of transition metal catalysis. However, although achieving this process using metal-free organocatalysts is highly challenging, it could offer unique opportunities to discover novel bond forming strategies in organic synthesis. Here we report a new amine catalysed direct stereoselective C-H alpha-arylation reaction of unmodified enals with bromoarenes. The power of this process, which involves an unprecedented iminium Michael-alkylation-enamine-retro-Michael cascade sequence, has been demonstrated in the context of direct alpha-functionalization reactions of simple, unmodified enals with 4-bromophenols, 1-bromo-2-naphthol and 3-bromoindoles under mild reaction conditions. Notably, the process can be used for highly stereoselective syntheses of non-readily accessible E isomers, which normally require the use of transition metal-promoted cross-couplings and functionalized enals. The results of these studies significantly expand the scope of aminocatalysis. PMID- 22068593 TI - Epithelial organisation revealed by a network of cellular contacts. AB - The emergence of differences in the arrangement of cells is the first step towards the establishment of many organs. Understanding this process is limited by the lack of systematic characterization of epithelial organisation. Here we apply network theory at the scale of individual cells to uncover patterns in cell to-cell contacts that govern epithelial organisation. We provide an objective characterisation of epithelia using network representation, where cells are nodes and cell contacts are links. The features of individual cells, together with attributes of the cellular network, produce a defining signature that distinguishes epithelia from different organs, species, developmental stages and genetic conditions. The approach permits characterization, quantification and classification of normal and perturbed epithelia, and establishes a framework for understanding molecular mechanisms that underpin the architecture of complex tissues. PMID- 22068594 TI - Differentially photo-crosslinked polymers enable self-assembling microfluidics. AB - An important feature of naturally self-assembled systems such as leaves and tissues is that they are curved and have embedded fluidic channels that enable the transport of nutrients to, or removal of waste from, specific three dimensional regions. Here we report the self-assembly of photopatterned polymers, and consequently microfluidic devices, into curved geometries. We discover that differentially photo-crosslinked SU-8 films spontaneously and reversibly curve on film de-solvation and re-solvation. Photolithographic patterning of the SU-8 films enables the self-assembly of cylinders, cubes and bidirectionally folded sheets. We integrate polydimethylsiloxane microfluidic channels with these SU-8 films to self-assemble curved microfluidic networks. PMID- 22068595 TI - A guideline for atomistic design and understanding of ultrahard nanomagnets. AB - Magnetic nanoparticles are of immense current interest because of their possible use in biomedical and technological applications. Here we demonstrate that the large magnetic anisotropy of FePt nanoparticles can be significantly modified by surface design. We employ X-ray absorption spectroscopy offering an element specific approach to magnetocrystalline anisotropy and the orbital magnetism. Experimental results on oxide-free FePt nanoparticles embedded in Al are compared with large-scale density functional theory calculations of the geometric- and spin-resolved electronic structure, which only recently have become possible on world-leading supercomputer architectures. The combination of both approaches yields a more detailed understanding that may open new ways for a microscopic design of magnetic nanoparticles and allows us to present three rules to achieve desired magnetic properties. In addition, concrete suggestions of capping materials for FePt nanoparticles are given for tailoring both magnetocrystalline anisotropy and magnetic moments. PMID- 22068596 TI - miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells. AB - miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development. PMID- 22068597 TI - Malaria parasite tyrosyl-tRNA synthetase secretion triggers pro-inflammatory responses. AB - Malaria infection triggers pro-inflammatory responses in humans that are detrimental to host health. Parasite-induced enhancement in cytokine levels correlate with malaria-associated pathologies. Here we show that parasite tyrosyl tRNA synthetase (PfTyrRS), a housekeeping protein translation enzyme, induces pro inflammatory responses from host immune cells. PfTyrRS exits from the parasite cytoplasm into the infected red blood cell (iRBC) cytoplasm, from where it is released into the extracellular medium on iRBC lysis. Using its ELR peptide motif, PfTyrRS specifically binds to and internalizes into host macrophages, leading to enhanced secretion of the pro-inflammatory cytokines TNF-alpha and IL 6. PfTyrRS-macrophage interaction also augments expression of adherence-linked host endothelial receptors ICAM-1 and VCAM-1. Our description of PfTyrRS as a parasite-secreted protein that triggers pro-inflammatory host responses, along with its atomic resolution crystal structure in complex with tyrosyl-adenylate, provides a novel platform for targeting PfTyrRS in anti-parasitic strategies. PMID- 22068598 TI - Extrasynaptic vesicle recycling in mature hippocampal neurons. AB - Fast neuronal signalling relies on highly regulated vesicle fusion and recycling at specialized presynaptic terminals. Recently, examples of non-classical neurotransmission have also been reported, where fusion of vesicles can occur at sites remote from conventional synapses. This has potentially broad biological implications, but the underlying mechanisms are not well established. Here we show that a complete vesicle recycling pathway can occur at discrete axonal sites in mature hippocampal neurons and that extrasynaptic fusion is a robust feature of native tissue. We demonstrate that laterally mobile vesicle clusters trafficking between synaptic terminals become transiently stabilized by evoked action potentials and undergo complete but delayed Ca(2+)-dependent fusion along axons. This fusion is associated with dynamic actin accumulation and, subsequently, vesicles can be locally recycled, re-acidified and re-used. Immunofluorescence and ultrastructural work demonstrates that extrasynaptic fusion sites can have apposed postsynaptic specializations, suggesting that mobile vesicle recycling may underlie highly dynamic neuron-neuron communication. PMID- 22068599 TI - Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision. AB - Retinal photoreceptors permit visual perception over a wide range of lighting conditions. Rods work best in dim, and cones in bright environments, with considerable functional overlap at intermediate (mesopic) light levels. At many sites in the outer and inner retina where rod and cone signals interact, gap junctions, particularly those containing Connexin36, have been identified. However, little is known about the dynamic processes associated with the convergence of rod and cone system signals into ON- and OFF-pathways. Here we show that proper cone vision under mesopic conditions requires rapid adaptational feedback modulation of rod output via hyperpolarization-activated and cyclic nucleotide-gated channels 1. When these channels are absent, sustained rod responses following bright light exposure saturate the retinal network, resulting in a loss of downstream cone signalling. By specific genetic and pharmacological ablation of key signal processing components, regular cone signalling can be restored, thereby identifying the sites involved in functional rod-cone interactions. PMID- 22068600 TI - The plasma 5'-AMP acts as a potential upstream regulator of hyperglycemia in type 2 diabetic mice. AB - Increased plasma free fatty acid (FFA) level is a hallmark of type 2 diabetes. However, the underlying molecular basis for FFA-caused hyperglycemia remains unclear. Here we identified plasma 5'-adenosine monophosphate (pAMP) markedly elevated in the plasma of type 2 diabetic mice. High levels of FFAs induced damage in vein endothelial cells and contributed to an increase in pAMP. Administration of synthetic 5'-AMP caused hyperglycemia and impaired insulin action in lean wild-type mice. 5'-AMP elevated blood glucose in mice deficient in adenosine receptors with equal efficiency as wild-type mice. The function of pAMP was initiated by the elevation of cellular adenosine levels, directly stimulating G-6-Pase enzyme activity, attenuating insulin-dependent GLUT4 translocation in skeletal muscle, and displaying a rapid and steep increase in blood glucose and a decrease in hepatic glycogen level. It was followed by an increase in the gene expression of hepatic Foxo1 and its targeting gene Pepck and G6Pase, which was similar to diabetic phenotype in db/db mice. Our results suggest that pAMP is a potential upstream regulator of hyperglycemia in type 2 diabetes. PMID- 22068602 TI - Altered REDD1, myostatin, and Akt/mTOR/FoxO/MAPK signaling in streptozotocin induced diabetic muscle atrophy. AB - Type 1 diabetes, if poorly controlled, leads to skeletal muscle atrophy, decreasing the quality of life. We aimed to search highly responsive genes in diabetic muscle atrophy in a common diabetes model and to further characterize associated signaling pathways. Mice were killed 1, 3, or 5 wk after streptozotocin or control. Gene expression of calf muscles was analyzed using microarray and protein signaling with Western blotting. We identified translational repressor protein REDD1 (regulated in development and DNA damage responses) that increased seven- to eightfold and was associated with muscle atrophy in diabetes. The diabetes-induced increase in REDD1 was confirmed at the protein level. This result was accompanied by the increased gene expression of DNA damage/repair pathways and decreased expression in ATP production pathways. Concomitantly, increased phosphorylation of AMPK and dephosphorylation of the Akt/mTOR/S6K1/FoxO pathway of proteins were observed together with increased protein ubiquitination. These changes were especially evident during the first 3 wk, along with the strong decrease in muscle mass. Diabetes also induced an increase in myostatin protein and decreased MAPK signaling. These, together with decreased serum insulin and increased serum glucose, remained altered throughout the 5-wk period. In conclusion, diabetic myopathy induced by streptozotocin led to alteration of multiple signaling pathways. Of those, increased REDD1 and myostatin together with decreased Akt/mTOR/FoxO signaling are associated with diabetic muscle atrophy. The increased REDD1 and decreased Akt/mTOR/FoxO signaling followed a similar time course and thus may be explained, in part, by increased expression of genes in DNA damage/repair and possibly also decrease in ATP-production pathways. PMID- 22068601 TI - Gestational-neonatal iron deficiency suppresses and iron treatment reactivates IGF signaling in developing rat hippocampus. AB - Gestational-neonatal iron deficiency, a common micronutrient deficiency affecting the offspring of more than 30% of pregnancies worldwide, leads to long-term cognitive and behavioral abnormalities. Preclinical models of gestational neonatal iron deficiency result in reduced energy metabolism and expression of genes critical for neuronal plasticity and cognitive function, which are associated with a smaller hippocampal volume and abnormal neuronal dendrite growth. Because insulin-like growth factor (IGF) modulates early postnatal cellular growth, differentiation, and survival, we used a dietary-induced rat model to assess the effects of gestational iron deficiency on activity of the IGF system. We hypothesized that gestational iron deficiency attenuates postnatal hippocampal IGF signaling and results in downstream effects that contribute to hippocampal anatomic and functional deficits. At postnatal day (P) 15 untreated gestational-neonatal iron deficiency markedly suppressed hippocampal IGF activation and protein kinase B signaling, and reduced neurogenesis, while elevating extracellular signal-regulated kinase 1/2 signaling and hypoxia inducible factor-1alpha expression. Iron treatment beginning at P7 restored IGF signaling, increased neurogenesis, and normalized all parameters by the end of rapid hippocampal differentiation (P30). Expression of the neuron-specific synaptogenesis marker, disc-large homolog 4 (PSD95), increased more rapidly than the glia-specific myelination marker, myelin basic protein, following iron treatment, suggesting a more robust response to iron therapy in IGF-I-dependent neurons than IGF-II-dependent glia. Collectively, our findings suggest that IGF dysfunction is in part responsible for hippocampal abnormalities in untreated iron deficiency. Early postnatal iron treatment of gestational iron deficiency reactivates the IGF system and promotes neurogenesis and differentiation in the hippocampus during a critical developmental period. PMID- 22068603 TI - Myofibrillar distribution of succinate dehydrogenase activity and lipid stores differs in skeletal muscle tissue of paraplegic subjects. AB - Lack of physical activity has been related to an increased risk of developing insulin resistance. This study aimed to assess the impact of chronic muscle deconditioning on whole body insulin sensitivity, muscle oxidative capacity, and intramyocellular lipid (IMCL) content in subjects with paraplegia. Nine subjects with paraplegia and nine able-bodied, lean controls were recruited. An oral glucose tolerance test was performed to assess whole body insulin sensitivity. IMCL content was determined both in vivo and in vitro using (1)H-magnetic resonance spectroscopy and fluorescence microscopy, respectively. Muscle biopsy samples were stained for succinate dehydrogenase (SDH) activity to measure muscle fiber oxidative capacity. Subcellular distributions of IMCL and SDH activity were determined by defining subsarcolemmal and intermyofibrillar areas on histological samples. SDH activity was 57 +/- 14% lower in muscle fibers derived from subjects with paraplegia when compared with controls (P < 0.05), but IMCL content and whole body insulin sensitivity did not differ between groups. In muscle fibers taken from controls, both SDH activity and IMCL content were higher in the subsarcolemmal region than in the intermyofibrillar area. This typical subcellular SDH and IMCL distribution pattern was lost in muscle fibers collected from subjects with paraplegia and had changed toward a more uniform distribution. In conclusion, the lower metabolic demand in deconditioned muscle of subjects with paraplegia results in a significant decline in muscle fiber oxidative capacity and is accompanied by changes in the subcellular distribution patterns of SDH activity and IMCL. However, loss of muscle activity due to paraplegia is not associated with substantial lipid accumulation in skeletal muscle tissue. PMID- 22068605 TI - Validity of particle size analysis techniques for measurement of the attrition that occurs during vacuum agitated powder drying of needle-shaped particles. AB - Analysis of needle-shaped particles of cellobiose octaacetate (COA) obtained from vacuum agitated drying experiments was performed using three particle size analysis techniques: laser diffraction (LD), focused beam reflectance measurements (FBRM) and dynamic image analysis. Comparative measurements were also made for various size fractions of granular particles of microcrystalline cellulose. The study demonstrated that the light scattering particle size methods (LD and FBRM) can be used qualitatively to study the attrition that occurs during drying of needle-shaped particles, however, for full quantitative analysis, image analysis is required. The algorithm used in analysis of LD data assumes the scattering particles are spherical regardless of the actual shape of the particles under evaluation. FBRM measures a chord length distribution (CLD) rather than the particle size distribution (PSD), which in the case of needles is weighted towards the needle width rather than their length. Dynamic image analysis allowed evaluation of the particles based on attributes of the needles such as length (e.g. the maximum Feret diameter) or width (e.g. the minimum Feret diameter) and as such, was the most informative of the techniques for the analysis of attrition that occurred during drying. PMID- 22068604 TI - Ghrelin-mediated sympathoinhibition and suppression of inflammation in sepsis. AB - Sepsis, a systemic inflammatory response to infection, continues to carry a high mortality despite advances in critical care medicine. Elevated sympathetic nerve activity in sepsis has been shown to contribute to early hepatocellular dysfunction and subsequently multiple organ failure, resulting in a poor prognosis, especially in the elderly. Thus, suppression of sympathetic nerve activity represents a novel therapeutic option for sepsis. Ghrelin is a 28-amino acid peptide shown to inhibit sympathetic nerve activity and inflammation in animal models of tissue injury. Age-related ghrelin hyporesponsiveness has also been shown to exacerbate sepsis. However, the mechanistic relationship between ghrelin-mediated sympathoinhibition and suppression of inflammation remains poorly understood. This review assesses the therapeutic potential of ghrelin in sepsis in the context of the neuroanatomical and molecular basis of ghrelin mediated suppression of inflammation through inhibition of central sympathetic outflow. PMID- 22068606 TI - Chemo-enzymatic syntheses of drimane-type sesquiterpenes and the fundamental core of hongoquercin meroterpenoid by recombinant squalene-hopene cyclase. AB - Squalene-hopene cyclase (SHC) converts squalene (C(30)) into pentacyclic triterpenes of hopene and hopanol. A linear sesquiterpene, (6E,10E)-2,6,10 trimethyldodeca-2,6,10-triene, underwent cyclization catalyzed by SHC, affording the following six bicyclic sesquiterpenes (drimane skeleton) in relatively high yield (68%): drim-7(8)-ene, drim-8(12)-ene, drim-8(9)-ene, driman-8alpha-ol, driman-8beta-ol, and the novel sesquiterpene, named quasiclerodane, the skeleton of which is analogous to that of clerodane diterpene. To extend the scope of the enzymatic syntheses, acyclic sesquiterpenes to which a phenol moiety was appended were subjected to the enzymatic reaction catalyzed by SHC. The cyclic meroterpene core present in hongoquercins A and B was successfully prepared. The formation mechanisms of drimane-type sesquiterpenes and the cyclic meroterpene core of hongoquercins A and B are discussed. PMID- 22068607 TI - Off-pump versus on-pump coronary artery bypass surgery in patients aged 80 years and older: institutional results and meta-analysis. AB - Patients aged >=80 years are at high risk of adverse events after coronary artery bypass grafting. This study was performed to evaluate whether off-pump coronary artery bypass surgery (OPCAB) is superior to conventional surgery (CCAB) in these high-risk patients. The outcome of 185 patients aged >=80 years who underwent OPCAB or CCAB at our institution was reviewed and a meta-analysis on this issue was performed. Similar immediate postoperative results were observed after OPCAB and CCAB at our institution, despite significantly different operative risk (mean logistic EuroSCORE, OPCAB 20.3% vs CCAB 13.4%, P = 0.003). Among 56 propensity score matched pairs a trend toward lower postoperative stroke (0%, 95% CI 0-0 vs 3.6%, 95% CI 0-10.0, P = 0.50) was observed after OPCAB. No significant differences were observed in the other outcome end points. Five-year survival was 81.0% after OPCAB and 78.1% after CCAB (P = 0.239). Pooled analysis of eight studies including 3416 patients showed a significantly higher risk of postoperative stroke after CCAB (pooled rates: 4.2%, 95% confidence interval (95% CI) 2.4-7.1 vs 1.5%, 95% CI 0.9-2.5, risk ratio (RR) 2.15, 95% CI 1.17-3.96, P = 0.01). A trend toward higher immediate postoperative mortality was observed after CCAB (15 studies including 4409 patients, pooled rates: 6.5%, 95% CI 5.2-8.0 vs 5.6%, 95% CI 4.2-7.4, RR 1.29, 95% CI 0.86-1.93, P = 0.21). Generic inverse variance analysis showed similar intermediate survival after CCAB and OPCAB (RR 1.31, 95% CI 0.85-2.01, P = 0.22). At 2 years, survival was 82.8% (95% CI 76.4 89.2) after CCAB and 88.3% (95% CI 82.9-93.7) after OPCAB. Current results indicate that OPCAB compared with CCAB in patients aged >=80 years is associated with significantly lower postoperative stroke and with a trend toward better early survival. However, suboptimal quality of the available studies, particularly the lack of comparability of the study groups, prevents conclusive results on this controversial issue. PMID- 22068608 TI - Intra-aortic balloon pumping reduces the increased arterial load caused by acute cardiac depression, modifying central and peripheral load determinants in a time- and flow-related way. AB - The mechanisms that explain intra-aortic balloon pumping (IABP) effects are not completely understood, and attributing them only to pressure-associated changes in cardiac function would be an oversimplification. Since IABP modifies the aortic and systemic blood-flow pattern, flow-related effects could be expected. To characterize effects of acute heart failure (AHF) on the arterial biomechanics; IABP effects on the arterial biomechanics during AHF, and their potential time-dependence; the association between hemodynamics and biomechanical changes during AHF and IABP. Sheep (n = 6) aortic pressure, flow, and diameter were measured: (1) before (Basal) and (2) 1-3 (HF(1-3)) and 28-30 (HF(28-30)) min after starting halothane to induce AHF; and (3) at specific times (1-3, 14-15 and 28-30 min) during IABP assistance. Calculus: aortic characteristic impedance (Z(c)), beta stiffness (beta), incremental (E(INC)) and pressure-strain elastic modulus (E(P)); total arterial compliance (C(G)), total systemic vascular resistance and wave propagation parameters. (1) AHF resulted in an acute increase in aortic and systemic stiffness (HF(28-30) % changes with respect to Basal conditions: beta +217%, E (P) +143%, E(INC) +101%, Z(c) +52%, C(G) -13%), associated with the reduction in the aortic blood flow; (2) during AHF IABP resulted in acute beneficial changes aortic and systemic biomechanics (% changes in IABP(1-3) with respect HF(28-30): beta -62%, E(P) -68%, E (INC) -66%, Z(c) 38%, C(G) 66%), and in wave propagation parameters, (3) IABP-related changes were time-dependent and associated with changes in aortic blood flow. Aortic and systemic biomechanical and impedance properties are detrimentally modified during AHF, being the changes rapidly reverted during IABP. IABP-related beneficial changes in arterial biomechanics were time-dependent and associated with IABP capability to increase blood flow. PMID- 22068609 TI - Multivessel percutaneous coronary intervention in patients with stable angina: a common approach? Lessons learned from the EHS PCI registry. AB - The aim of this study was to evaluate clinical characteristics, procedural details, and outcomes of patients undergoing elective multivessel percutaneous coronary intervention (MV-PCI) in Europe. A total of 7113 patients with stable coronary artery disease and at least two major epicardial vessels with >= 70% stenosis were included in this analysis of the contemporary Euro Heart Survey PCI registry. Patients undergoing MV-PCI (n = 3376, 47.5%) were compared with those with single-vessel PCI (SV-PCI) (n = 3737, 52.5%). Patients with MV-PCI were more likely to have congestive heart failure, whereas those with SV-PCI more often suffered from noncardiac comorbidities. Hospital mortality (0.1% vs 0.3%) and the incidence of nonfatal postprocedural myocardial infarction (1.0% vs 0.7%) were low in patients with MV-PCI and SV-PCI. In the multivariate analysis, no significant difference in the incidence of hospital death (odds ratio (OR) 0.44, 95% confidence interval (CI) 0.15-1.27) could be observed between the two groups. However, the risk for postprocedural myocardial infarction (OR 1.57, 95% CI 0.93 2.67) tended to be higher among patients undergoing MV-PCI. Independent determinants for performing MV-PCI were age, comorbidities, and coronary anatomy. In Europe almost half of all patients with multivessel disease were treated with MV-PCI. Hospital complications were low, but a trend toward a higher rate of postprocedural myocardial infarctions was seen in patients with MV-PCI. PMID- 22068610 TI - Homeostatic regulation of NCAM polysialylation is critical for correct synaptic targeting. AB - During development, axonal projections have a remarkable ability to innervate correct dendritic subcompartments of their target neurons and to form regular neuronal circuits. Altered axonal targeting with formation of synapses on inappropriate neurons may result in neurodevelopmental sequelae, leading to psychiatric disorders. Here we show that altering the expression level of the polysialic acid moiety, which is a developmentally regulated, posttranslational modification of the neural cell adhesion molecule NCAM, critically affects correct circuit formation. Using a chemically modified sialic acid precursor (N propyl-D: -mannosamine), we inhibited the polysialyltransferase ST8SiaII, the principal enzyme involved in polysialylation during development, at selected developmental time-points. This treatment altered NCAM polysialylation while NCAM expression was not affected. Altered polysialylation resulted in an aberrant mossy fiber projection that formed glutamatergic terminals on pyramidal neurons of the CA1 region in organotypic slice cultures and in vivo. Electrophysiological recordings revealed that the ectopic terminals on CA1 pyramids were functional and displayed characteristics of mossy fiber synapses. Moreover, ultrastructural examination indicated a "mossy fiber synapse"-like morphology. We thus conclude that homeostatic regulation of the amount of synthesized polysialic acid at specific developmental stages is essential for correct synaptic targeting and circuit formation during hippocampal development. PMID- 22068611 TI - The role of mammalian target of rapamycin (mTOR) in the regulation of pancreatic beta-cell mass: implications in the development of type-2 diabetes. AB - Type-2 diabetes mellitus (T2DM) is a disorder that is characterized by high blood glucose concentration in the context of insulin resistance and/or relative insulin deficiency. It causes metabolic changes that lead to the damage and functional impairment of organs and tissues resulting in increased morbidity and mortality. It is this form of diabetes whose prevalence is increasing at an alarming rate due to the 'obesity epidemic', as obesity is a key risk factor in the development of insulin resistance. However, the majority of individuals who have insulin resistance do not develop diabetes due to a compensatory increase in insulin secretion in response to an increase in insulin demand. This adaptive response is sustained by an increase in both beta-cell function and mass. Importantly, there is increasing evidence that the Serine/Threonine kinase mammalian target of rapamycin (mTOR) plays a key role in the regulation of beta cell mass and therefore likely plays a critical role in beta-cell adaptation. Therefore, the primary focus of this review is to summarize our current understanding of the role of mTOR in stimulating pancreatic beta-cell mass and thus, in the prevention of type-2 diabetes. PMID- 22068612 TI - NFkappaB and HIF display synergistic behaviour during hypoxic inflammation. AB - The oxygen-sensitive transcription factor hypoxia inducible factor (HIF) is a key regulator of gene expression during adaptation to hypoxia. Crucially, inflamed tissue often displays regions of prominent hypoxia. Recent studies have shown HIF signalling is intricately linked to that of the pro-inflammatory transcription factor nuclear factor kappa B (NFkappaB) during hypoxic inflammation. We describe the relative temporal contributions of each to hypoxia-induced inflammatory gene expression and investigate the level of crosstalk between the two pathways using a novel Gaussia princeps luciferase (Gluc) reporter system. Under the control of an active promoter, Gluc is expressed and secreted into the cell culture media, where it can be sampled and measured over time. Thus, Gluc constructs under the control of either HIF or NFkappaB were used to resolve their temporal transcriptional dynamics in response to hypoxia and to cytokine stimuli, respectively. We also investigated the interactions between HIF and NFkappaB activities using a construct containing the sequence from the promoter of the inflammatory gene cyclooxygenase 2 (COX-2), which includes functionally active binding sites for both HIF and NFkappaB. Finally, based on our experimental data, we constructed a mathematical model of the binding affinities of HIF and NFkappaB to their respective response elements to analyse transcriptional crosstalk. Taken together, these data reveal distinct temporal HIF and NFkappaB transcriptional activities in response to hypoxic inflammation. Furthermore, we demonstrate synergistic activity between these two transcription factors on the regulation of the COX-2 promoter, implicating a co-ordinated role for both HIF and NFkappaB in the expression of COX-2 in hypoxic inflammation. PMID- 22068614 TI - Lipid infiltration in the parotid glands: a clinical manifestation of metabolic syndrome. AB - BACKGROUND: The clinical features of lipid infiltration in the parotid glands (LIPG) have not been studied. Monitoring of atomic-bomb survivors for late effects of radiation exposure has provided the opportunity to review the clinical findings of LIPG. METHODS: A total of 992 atomic-bomb survivors in Nagasaki, Japan underwent lachrymal and salivary secretion tests and anthropometric, biochemical, and abdominal ultrasonographic examinations between 2002 and 2004. Among 465 subjects who had reduced tear and/or salivary excretion, 176 subjects took a salivary magnetic resonance imaging (MRI) examination. RESULTS: LIPG was detected in 53 of the 176 subjects who had salivary MRI. LIPG cases showed a preponderance of females and fatty liver compared with the subjects without LIPG. Age-and-sex-adjusted regression analysis revealed that body mass index (BMI), low density lipoprotein cholesterol, triglycerides, hemoglobin A1c, and C-reactive protein were higher, whereas high-density lipoprotein cholesterol and adiponectin were lower, in the subjects with LIPG. Multivariate logistic regression analysis showed that BMI and fatty liver were mutually associated with LIPG independently from radiation dose. CONCLUSIONS: LIPG associated with BMI, fatty liver, and coronary risk factors was a clinical manifestation of metabolic syndrome. PMID- 22068615 TI - Role of the CAG repeat polymorphism of the androgen receptor gene in polycystic ovary syndrome (PCOS). AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS. METHODS: In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay. RESULTS: Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002). CONCLUSIONS: The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome's phenotype, contributing to its clinical heterogeneity and associated metabolic consequences. PMID- 22068613 TI - Cycling or not cycling: cell cycle regulatory molecules and adult neurogenesis. AB - The adult brain most probably reaches its highest degree of plasticity with the lifelong generation and integration of new neurons in the hippocampus and olfactory system. Neural precursor cells (NPCs) residing both in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles continuously generate neurons that populate the dentate gyrus and the olfactory bulb, respectively. The regulation of NPC proliferation in the adult brain has been widely investigated in the past few years. Yet, the intrinsic cell cycle machinery underlying NPC proliferation remains largely unexplored. In this review, we discuss the cell cycle components that are involved in the regulation of NPC proliferation in both neurogenic areas of the adult brain. PMID- 22068617 TI - An Integrated Framework for Parameter-based Optimization of Scientific Workflows. AB - Data analysis processes in scientific applications can be expressed as coarse grain workflows of complex data processing operations with data flow dependencies between them. Performance optimization of these workflows can be viewed as a search for a set of optimal values in a multi-dimensional parameter space. While some performance parameters such as grouping of workflow components and their mapping to machines do not a ect the accuracy of the output, others may dictate trading the output quality of individual components (and of the whole workflow) for performance. This paper describes an integrated framework which is capable of supporting performance optimizations along multiple dimensions of the parameter space. Using two real-world applications in the spatial data analysis domain, we present an experimental evaluation of the proposed framework. PMID- 22068616 TI - Reduction of insulin signaling upregulates angiopoietin-like protein 4 through elevated free fatty acids in diabetic mice. AB - BACKGROUND: Angiopoietin-like protein 4 (Angptl4) is thought to cause an increase in serum triglyceride levels. In the present study, we elucidated Angptl4 expression in the mouse models of type 1 and type 2 diabetes mellitus, and investigated the possible mechanisms involved. METHODS: Type 1 diabetes was induced in C57BL/6 J mice by treating them with streptozotocin (STZ). Type 2 diabetes was induced by feeding the mice a high-fat diet (HFD) for 18 weeks. RESULTS: The levels of Angptl4 mRNA expression in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) were found to increase in the STZ diabetic mice relative to control mice. This effect was attenuated by insulin administration. In the HFD diabetic mice, the Angptl4 mRNA expression levels were increased in liver, WAT, and BAT. Treatment with metformin for 4 weeks attenuated the increased levels of Angptl4 mRNA. Fatty acids (FAs) such as palmitate and linoleate induced Angptl4 mRNA expression in H4IIE hepatoma cells and 3T3-L1 adipocytes. Treatment with insulin but not metformin attenuated FA-induced Angptl4 mRNA expression in H4IIE. Both insulin and metformin did not influence the effect of FAs in 3T3-L1 cells. CONCLUSION: These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice. PMID- 22068618 TI - Stigmasterol-based novel low molecular weight/mass organic gelators. AB - Conjugates consisting of stigmasterol and L-phenylalanine, interconnected through short-chained dicarboxylic acyls by ester and amide bonds, respectively, were synthesized as potential low molecular weight/mass organic gelators (LMWGs/LMMGs). Their physico-chemical properties were subjected to investigation, especially their ability to form gels reversibly based on changes of the environmental conditions. Other self-assembly properties detectable by UV-VIS traces were measured in systems consisting of two miscible solvents (water/acetonitrile) with varying solvent ratios and using constant concentrations of the studied compounds. Partition and diffusion coefficients and solubility in water were calculated for the target conjugates. The conjugate 3a was the only compound from this series capable of forming a gel in 1-octanol. All three conjugates 3a-3c displayed supramolecular characteristics in the UV-VIS spectra. PMID- 22068619 TI - Synthesis and biological evaluation of 3-substituted-indolin-2-one derivatives containing chloropyrrole moieties. AB - Eighteen novel 3-substituted-indolin-2-ones containing chloropyrroles were synthesized and their biological activities were evaluated. The presence of a chlorine atom on the pyrrole ring was crucial to reduce cardiotoxicity. The presence of a 2-(ethyl-amino)ethylcarbamoyl group as a substituent at the C-4' position of the pyrrole enhanced the antitumor activities notably. IC50 values as low as 0.32, 0.67, 1.19 and 1.22 MUM were achieved against non-small cell lung cancer (A549), oral epithelial (KB), melanoma (K111) and large cell lung cancer cell lines (NCI-H460), respectively. PMID- 22068620 TI - Necessary health care and basic needs: health insurance plans and essential benefits. AB - According to HealthCare.gov, by improving access to quality health for all Americans, the Affordable Care Act (ACA) will reduce disparities in health insurance coverage. One way this will happen under the provisions of the ACA is by creating a new health insurance marketplace (a health insurance exchange) by 2014 in which "all people will have a choice for quality, affordable health insurance even if a job loss, job switch, move or illness occurs". This does not mean that everyone will have whatever insurance coverage he or she wants. The provisions of the ACA require that each of the four benefit categories of plans (known as bronze, silver, gold and platinum) provides no less than the benefits available in an "essential health benefits package". However, without a clear understanding of what criteria must be satisfied for health care to be essential, the ACA's requirement is much too vague and open to multiple, potentially conflicting interpretations. Indeed, without such understanding, in the rush to provide health insurance coverage to as many people as is economically feasible, we may replace one kind of disparity (lack of health insurance) with another kind of disparity (lack of adequate health insurance). Thus, this paper explores the concept of "essential benefits", arguing that the "essential health benefits package" in the ACA should be one that optimally satisfies the basic needs of the people covered. PMID- 22068621 TI - Obesity is associated with lower mortality risk in elderly diabetic subjects: the Casale Monferrato study. AB - The relationship between obesity and mortality in people with type 2 diabetes has not been definitely assessed. We have examined this issue in a well-characterized population-based cohort of Mediterranean diabetic people. Standardized anthropometric data from the population-based Casale Monferrato Study have been prospectively analyzed. The cohort included 1,475 people (62.6% aged >=65 years) who had been recruited in 1991 and followed-up to December 31, 2006. Cox proportional hazards modeling was employed to estimate the independent associations between all-cause and cardiovascular mortality and BMI. Out of 1,475 people, 972 deaths occurred during a 15-year follow-up. Cox regression analyses showed that with respect to BMI <24.2 kg/m(2), values of 30.0 kg/m(2) and over were associated with lower all-cause and cardiovascular mortality risk (HR = 0.68, 95% CI 0.56-0.85, P for trend = 0.001; HR = 0.59, 0.44-0.80, P for trend = 0.002), independently of classical and new risk factors. As interaction between age and BMI was significant, we performed a stratified analysis by age, providing evidence that our finding was entirely due to a significant protective effect of BMI of 30.0 kg/m(2) and over in the elderly (all-cause mortality HR = 0.75, 95% CI 0.58-0.96; cardiovascular mortality HR = 0.67, 95% CI 0.45-0.95). In contrast, obesity was not significantly associated with mortality risk in diabetic subjects aged <65 years. Results were confirmed even excluding from the analysis individuals who died within 2 years of follow-up, smokers and those with CHD. In Mediterranean diabetic people aged >=65 years, obesity is significantly associated with lower 15-year mortality risk. In contrast, it was not significantly associated with mortality risk in diabetic subjects aged <65 years. As more than two-thirds of people with type 2 diabetes are elderly, our findings, if confirmed, could have clinical implications. PMID- 22068622 TI - ACP1-ADA1 interaction in type 2 diabetes: a study in coronary artery disease. PMID- 22068623 TI - Retinal heat shock protein 25 in early experimental diabetes. AB - Diabetic retinopathy is the leading cause of blindness in adults, and oxidative stress has been pathogenically associated with retinal neurodegeneration. Cellular stresses induce expression of heat shock proteins (HSPs) and this results in cytoprotection. Our aim was to assess retinal expression of HSP25 in early experimental diabetes. Mice were rendered diabetic by streptozotocin injection. Ten weeks after diabetes onset retinal HSP25 expression were studied by real-time PCR, immunoblotting and immunohistochemistry (IHC). Expression of nitrotyrosine and Cu/Zn superoxide dismutase (SOD), was assessed by IHC and apoptosis by TUNEL. Retinal HSP25 mRNA and protein expression was significantly increased in diabetic as compared to non-diabetic animals and localised predominantly within the retinal ganglion cells (RGC) layer. This was paralleled overexpression of nitrotyrosine and SOD and enhanced apoptosis. In early experimental diabetes, HSP25 is overexpressed in the RGC layer in parallel with markers of oxidative stress and apoptosis. PMID- 22068624 TI - The collaborative role of molecular conformation and energetics in the binding of gas-phase non-covalent polymer/amine complexes. AB - A large series of similar non-covalent complexes were probed using ion mobility spectrometry, molecular mechanics/molecular dynamics (MM/MD), electrospray-tandem mass spectrometry (ESI-MS/MS) and RRKM theory in order to determine the effects of charge state and charge location upon the conformation, the 0 K activation energy (E(0)) and the entropy of activation (DeltaS(?)) of the dissociation of these complexes. The non-covalent complexes consisted of poly(methylmethacrylate) oligomers and singly and doubly charged diaminoalkanes of varying length. This allowed for control of the charge separation within the complexes, as well as the size of the complex. A destabilizing effect was observed in complexes containing protons in close proximity, and/or short oligomers. Interestingly, a multiple charge stabilizing effect was observed when charge sites were sufficiently separated and/or when the polymer moiety of the complex was large. DeltaS(?) values of doubly charged complexes showed a greater increase with increasing polymer size in comparison to singly charged complexes. This entropic observation is explained by structure, where IMS and MM/MD determined that the charge location was the determining factor of the overall conformation of these complexes and multiple charging resulted in more rigid arrangements. Dissociation of a tightly bound complex is more entropically favorable than a loosely bound complex. Also presented is a MM/MD refinement regime derived from IMS measurements. PMID- 22068625 TI - Arterial spin labeling of hemangioblastoma: differentiation from metastatic brain tumors based on quantitative blood flow measurement. AB - INTRODUCTION: Hemangioblastoma and metastatic tumors are the major differential diagnoses for the posterior fossa tumors in adults. Our purpose was to evaluate the efficacy of ASL in differentiating hemangioblastomas from metastatic brain tumors. METHODS: A total of 19 patients including 5 with a hemangioblastomas and 14 with metastatic tumors (7 from lung cancer, 4 from breast cancer, 1 from RCC, 1 from gastric cancer, and 1 from unknown origin) were enrolled in this study. ASL was performed using a pulsed ASL method at a 3-T unit. aTBF was measured as a mean absolute blood flow value within a region of interest drawn in the tumor. In addition, rTBF was obtained by normalizing the aTBF by a blood flow measured in the normal-appearing cortical gray matter. The aTBF and rTBF values were compared between hemangioblastomas and metastatic tumors using Student's t test. RESULTS: Both the aTBF and rTBF values were significantly higher in hemangioblastomas (mean aTBF +/- SD = 437 +/- 274 mL/100 g/min, mean rTBF +/- SD = 7.96 +/- 3.12) in comparison with metastatic brain tumors (mean aTBF +/- SD = 125 +/- 134 mL/100 g/min, mean rTBF +/- SD = 2.98 +/- 3.91; p < 0.05, respectively). However, a metastasis from RCC showed very high aTBF (559 mL/100 g/min) and rTBF (16.2). CONCLUSION: Our results demonstrated that ASL provides useful information to differentiate between hemangioblastomas and metastatic brain tumors. Metastasis from RCC may mimic hemangioblastoma on ASL blood flow measurement. PMID- 22068626 TI - Degradation of reactive dyes in a photocatalytic circulating-bed biofilm reactor. AB - Decolorization and mineralization of reactive dyes by intimately coupled TiO2 photocatalysis and biodegradation (ICPB) on a novel TiO2-coated biofilm carrier were investigated in a photocatalytic circulating-bed biofilm reactor (PCBBR). Two typical reactive dyes--Reactive Black 5 (RB5) and Reactive Yellow 86 (RY86)- showed similar first-order kinetics when being photocatalytically decolorized at low pH (~4-5) in batch experiments. Photocatalytic decolorization was inhibited at neutral pH in the presence of phosphate or carbonate buffer, presumably due to electrostatic repulsion from negatively charged surface sites on TiO2, radical scavenging by phosphate or carbonate, or both. Therefore, continuous PCBBR experiments were carried out at a low pH (~4.5) to maintain high photocatalytic efficiency. In the PCBBR, photocatalysis alone with TiO2-coated carriers could remove target compound RB5 and COD by 97% and 47%, respectively. Addition of biofilm inside macroporous carriers maintained a similar RB5 removal efficiency, but COD removal increased to 65%, which is evidence of ICPB despite the low pH. ICPB was further proven by finding microorganisms inside carriers at the end of the PCBBR experiments. A proposed ICPB pathway for RB5 suggests that a major intermediate, a naphthol derivative, was responsible for most of the residual COD, while most of the nitrogen in the azo-bonds (-N=N-) was oxidized to N2. PMID- 22068628 TI - An overview of letrozole in postmenopausal women with hormone-responsive breast cancer. AB - Third-generation aromatase inhibitors (AIs) have proven to be superior to tamoxifen in terms of time to disease progression in patients with hormone receptor (HR) positive (HR+) status and, nowadays, are used in the adjuvant and neoadjuvant settings, and first-line therapy for advanced breast cancer. Letrozole is a third generation AI, as are anastrozole and exemestane. In the past, clinical studies had demonstrated that letrozole was effective as a second line treatment of metastatic breast cancer. In this paper, pharmacokinetic and pharmacodynamic properties of letrozole are reviewed along with its activity in preclinical and clinical settings. Additionally, the results of important clinical trials such as Breast International Group (BIG) 1-98, which tested the optimal initial adjuvant endocrine treatment and the sequential therapy with letrozole and tamoxifen, MA-17 that evaluates the benefits of extended adjuvant therapy, and other important studies in advanced and neoadjuvant disease, are reviewed. Safety comparisons of treatments are also addressed. Interestingly, about 50% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers are HR+. However, HER2 positivity is a marker of antiestrogen treatment resistance. Because of this, a dual treatment is a logical approach when both receptors are overexpressed. The combination of lapatinib and letrozole leads to a significant improvement in the overall disease outcome. Also, the combination of everolimus plus letrozole has been tested in this setting. In fact, the coadministration of both agents seems to increase the efficacy of letrozole in newly-diagnosed HR+ patients. Once resistance to sequential trastuzumab and AI as monotherapy has been found, trastuzumab and letrozole combined in HR+ and HER2+ patients with advanced breast cancer can overcome resistance to both drugs administered as single agents, according to recently reported results. PMID- 22068629 TI - Final report of the Amended Safety Assessment of PVM/MA copolymer and its related salts and esters as used in cosmetics. AB - Polyvinyl methyl ether/maleic acid (PVM/MA) copolymer, and its related salts and esters, are used in cosmetics, mainly as binders, film formers, and hair fixatives. Animal and human data relevant to the use of these ingredients in cosmetic products were reviewed by the CIR Expert Panel. The Panel concluded that these ingredients are safe for use in cosmetic products. PMID- 22068630 TI - Annual Review of Cosmetic Ingredient Safety Assessments: 2007-2010. PMID- 22068627 TI - Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson's disease, Alzheimer's disease and autism spectrum disorder. AB - The nematode Caenorhabditis elegans has a very well-defined and genetically tractable nervous system which offers an effective model to explore basic mechanistic pathways that might be underpin complex human neurological diseases. Here, the role C. elegans is playing in understanding two neurodegenerative conditions, Parkinson's and Alzheimer's disease (AD), and a complex neurological condition, autism, is used as an exemplar of the utility of this model system. C. elegans is an imperfect model of Parkinson's disease because it lacks orthologues of the human disease-related genes PARK1 and LRRK2 which are linked to the autosomal dominant form of this disease. Despite this fact, the nematode is a good model because it allows transgenic expression of these human genes and the study of the impact on dopaminergic neurons in several genetic backgrounds and environmental conditions. For AD, C. elegans has orthologues of the amyloid precursor protein and both human presenilins, PS1 and PS2. In addition, many of the neurotoxic properties linked with Abeta amyloid and tau peptides can be studied in the nematode. Autism spectrum disorder is a complex neurodevelopmental disorder characterised by impairments in human social interaction, difficulties in communication, and restrictive and repetitive behaviours. Establishing C. elegans as a model for this complex behavioural disorder is difficult; however, abnormalities in neuronal synaptic communication are implicated in the aetiology of the disorder. Numerous studies have associated autism with mutations in several genes involved in excitatory and inhibitory synapses in the mammalian brain, including neuroligin, neurexin and shank, for which there are C. elegans orthologues. Thus, several molecular pathways and behavioural phenotypes in C. elegans have been related to autism. In general, the nematode offers a series of advantages that combined with knowledge from other animal models and human research, provides a powerful complementary experimental approach for understanding the molecular mechanisms and underlying aetiology of complex neurological diseases. PMID- 22068631 TI - Adding to the mix: integrating ELSI into a National Nanoscale Science and Technology Center. AB - This paper describes issues associated with integrating the study of Ethical, Legal and Social Issues (ELSI) into ongoing scientific and technical research and describes an approach adopted by the authors for their own work with the center for nanophase materials sciences (CNMS) at the Oak Ridge national laboratory (ORNL). Four key questions are considered: (a) What is ELSI and how should it identify and address topics of interest for the CNMS? (b) What advantages accrue to incorporating ELSI into the CNMS? (c) How should the integration of ELSI into the CNMS take place? (d) How should one judge the effectiveness of the activity? We conclude that ELSI research is not a monolithic body of knowledge, but should be adapted to the question at hand. Our approach focuses on junctures in the R&D continuum at which key decisions occur, avoids topics of a purely ethical nature or advocacy, and seeks to gather data in ways that permit testing the validity of generalization. Integrating ELSI into the CNMS allows dealing with topics firmly grounded in science, offers concrete examples of potential downstream applications and provides access to the scientists using the CNMS and their insights and observations. As well, integration provides the opportunity for R&D managers to benefit from ELSI insights and the potential to modify R&D agendas. Successful integration is dependent on the particular ELSI question set that drives the project. In this case questions sought to identify key choices, information of value to scientists, institutional attributes, key attributes of the CNMS culture, and alternatives for communicating results. The opportunity to consult with scientists on ELSI implications is offered, but not promoted. Finally, ELSI effectiveness is judged by observing the use to which research products are put within the CNMS, ORNL, and the community of external scholars. PMID- 22068632 TI - Engagement agents in the making: on the front lines of socio-technical integration : commentary on: "Constructing productive engagement: pre-engagement tools for emerging technologies". AB - This commentary builds on Haico te Kulve and Arie Rip's (2011) notion of "engagement agents," individuals that must be able to move between multiple dimensions, or "levels" of research, innovation, and policy processes. The commentary compares and contrasts the role of the engagement agent within the Constructive Technology Assessment and integration approaches, and suggests that on-site integration research represents one way to transform both social and natural scientists into competent and informed "engagement agents," a new generation of researchers that possess the knowledge and capacities to forge "novel linkages" between the oftentimes disparate terrains of science, politics, and policy. PMID- 22068633 TI - Cell signalling: mTOR targets its own inhibitor. PMID- 22068634 TI - Evaluation of two Indian native chicken breeds for reproduction traits and heritability of juvenile growth traits. AB - The present study was conducted to evaluate two Indian native chicken breeds, namely, Aseel and Kadaknath for fertility, hatchability, genetic parameters of juvenile growth traits, and semen quality traits at the onset of sexual maturity. The fertility was similar in Aseel (86.96%) and Kadaknath (85.15%); however, a relatively higher hatchability was observed in Kadaknath (77.94%) than Aseel (70.74%). Heritability estimates of body weights at 4 weeks of age were almost similar in Aseel (0.37) and Kadaknath (0.39), while the estimate of body weight at 6 weeks of age was higher in Aseel (0.42) than Kadaknath (0.31). The heritability estimate of shank length at 6 weeks of age was lower in Aseel (0.16) compared to Kadaknath (0.35). The age at first egg in the flock was comparable in Aseel (148 days) and Kadaknath (150 days). Aseel breed with significantly (P <= 0.001) higher body weight, absolute and relative testes weights had significantly higher semen volume (P <= 0.05) and sperm motility (P <= 0.01) but had lower seminal plasma cholesterol level (P <= 0.05) as compared to Kadaknath. It can be concluded that there is a scope for genetic improvement of these two native breeds for juvenile growth traits since heritability estimates of these traits were relatively high. PMID- 22068635 TI - Identification of Pasteurella multocida capsular types isolated from rabbits and other domestic animals in Mexico with respiratory diseases. AB - Pasteurella multocida is the causative agent of pasteurellosis, a major disease in most domestic animals and livestock. In this study, a total of 34 isolates of P. multocida from rabbits and other domestic animals from Mexico with respiratory diseases underwent polymerase chain reaction-based capsular typing. One sheep isolate was found to belong to capsular serogroup D, whereas the rest of the rabbit, sheep, cattle, pig, goat, and duck isolates belonged to capsular serogroup A of P. multocida. This is the first report of capsular type A in P. multocida isolates from rabbits and duck origin in Mexico. PMID- 22068637 TI - The fiscal outcome of artificial conception in Brazil--creating citizens in developing countries. AB - BACKGROUND: Infertility is an important health issue, but only a small fraction of the affected population receives treatment in Brazil, because it is not covered by the government or private health insurance plans. We developed a generational accounting-based mathematical model to assess the direct economic result of creating a citizen through IVF in different economic scenarios, and the potential economic benefit generated by the individual and his/her future offspring. METHODS: A mathematical model analyzes the revenues and expenses of an IVF-conceived individual over his lifetime. We calculated the net present value (NPV) of an IVF-conceived citizen, and this value corresponds to the fiscal contribution to the government by an individual, from birth through his predicted life expectancy. The calculation used discount rates of 4.0 and 7.0% to depreciate the money value by time. RESULTS: A 4.0% discount rate represents the most favorable economic scenario in Brazil, and it results in an NPV of US$ 61 428. A 7.0% discount rate represents a less favorable economic reality, and it results in a debit of U$ 563, but this debt may be compensated by his/her future offspring. CONCLUSIONS: The fiscal contribution generated by each IVF-conceived citizen can justify an initial government investment in infertility treatment. Poor economic times in Brazil can sometimes result in a fiscal debt from each new IVF-conceived child, but this initial expenditure may be compensated by the fiscal contribution in the next generation. PMID- 22068636 TI - Seroprevalence of porcine reproductive and respiratory syndrome, Aujeszky's disease, and porcine parvovirus in replacement gilts in Thailand. AB - The present study investigated the seroprevalence of porcine reproductive and respiratory syndrome virus, Aujeszky's disease virus (ADV), and porcine parvovirus (PPV) in replacement gilts from selected five swine herds in Thailand. The study consisted of three parts. First, a retrospective data analysis on the seroprevalence of porcine reproductive and respiratory syndrome virus (PRRSV) and ADV glycoprotein I (gI) in gilts, sows, boars, nursery, and fattening pigs in five herds (n = 7,030). Second, a cross-sectional study on seroprevalence of PRRSV, ADV, and PPV (n = 200) in replacement gilts. Last, the seroprevalence of PRRSV, ADV, and PPV in gilts culled due to reproductive failure (n = 166). Across the herds, the seroprevalence of PRRSV and ADV was 79.3% and 5.3%, respectively. The cross-sectional study revealed that 87.5%, 4.0%, and 99.0% of the replacement gilts were infected with PRRSV, ADV, and PPV, respectively. In the gilts culled due to reproductive failure, the seroprevalence of PRRSV, ADV, and PPV was 73.5%, 28.3%, and 86.0%, respectively. Of these culled gilts, 75.5% had been infected with at least two viruses and 18.9% had been infected with all three viruses. It could be concluded that most of the replacement gilts were exposed to PRRSV (84%), PPV (97%), and ADV (4%) before entering the breeding house. PPV was an enzootic disease among the selected herds. The prevalence of ADV was higher in gilts culled due to reproductive disturbance than in the healthy gilts. PMID- 22068638 TI - Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial. AB - BACKGROUND: Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryo's spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers. METHODS: We conducted a single-centre, double-blinded, randomized controlled trial in which the NIR group was compared with a control group. The primary outcome was the clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. In the control group embryo selection was based only on traditional morphological evaluation while in the treatment group NIR spectroscopy was added to the morphological evaluation. RESULTS: The study was terminated early as the analysis of the Data Safety Monitoring Board showed a very low conditional power of superiority for the primary outcome. Of the 752 patients calculated to be included in the study, 164 and 163 patients were randomized into the NIR and control groups, respectively. No significant difference in the ongoing pregnancy rate per randomized patient was found between the NIR and the control group, 34.8 versus 35.6%, (P= 0.97). The proportional difference between the study groups mean was -0.8% (95% confidence interval -11.4 to 10.2). CONCLUSIONS: This study shows that adding NIR spectroscopy, in its present form, to embryo morphology does not improve the chance of a viable pregnancy when performing SET. The NIR technology appears to need further development before it can be used as an objective marker of embryo viability. CLINICAL TRIALS IDENTIFIER: ISRCTN23817363. PMID- 22068639 TI - Integrated ecological risk assessment of pesticides in tropical ecosystems: a case study with carbofuran in Brazil. AB - The aim of the present study is to contribute an ecologically relevant assessment of the ecotoxicological effects of pesticide applications in agricultural areas in the tropics, using an integrated approach with information gathered from soil and aquatic compartments. Carbofuran, an insecticide/nematicide used widely on sugarcane crops, was selected as a model substance. To evaluate the toxic effects of pesticide spraying for soil biota, as well as the potential indirect effects on aquatic biota resulting from surface runoff and/or leaching, field and laboratory (using a cost-effective simulator of pesticide applications) trials were performed. Standard ecotoxicological tests were performed with soil (Eisenia andrei, Folsomia candida, and Enchytraeus crypticus) and aquatic (Ceriodaphnia silvestrii) organisms, using serial dilutions of soil, eluate, leachate, and runoff samples. Among soil organisms, sensitivity was found to be E. crypticus < E. andrei < F. candida. Among the aqueous extracts, mortality of C. silvestrii was extreme in runoff samples, whereas eluates were by far the least toxic samples. A generally higher toxicity was found in the bioassays performed with samples from the field trial, indicating the need for improvements in the laboratory simulator. However, the tool developed proved to be valuable in evaluating the toxic effects of pesticide spraying in soils and the potential risks for aquatic compartments. PMID- 22068640 TI - Targeting GSTP1-1 induces JNK activation and leads to apoptosis in cisplatin sensitive and -resistant human osteosarcoma cell lines. AB - The effect of the glutathione transferase P1-1 (GSTP1-1) targeting has been investigated in both sensitive (U-2OS) and cisplatin-resistant (U-2OS/CDDP4 MUg) human osteosarcoma cell lines. Despite the different enzyme's content, inhibition of GSTP1-1 by 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) causes the activation of c-Jun N-terminal kinase (JNK) and apoptosis in both cell lines. However, different time courses of JNK activation and cell responses are observed. Whereas in the U-2OS/CDDP4 MUg cell line drug treatment results in an early increase of caspase activity and secondary necrosis, in the U-2OS cells it mainly causes an early cell cycle arrest followed by apoptosis. In order to elucidate the action mechanism of NBDHEX we performed a proteomic investigation by label-free nLC-MS(E). The high-throughput analysis associated with a bioinformatic tool suggested the involvement of the TNF receptor associated factor (TRAF) family in the cellular response to the drug treatment. We report experimental evidence of the interaction between GSTP1-1 and TRAF2 and we demonstrate that NBDHEX is able to dissociate the GSTP1-1 : TRAF2 complex. This restores the TRAF2 : ASK1 signaling, thereby leading to the simultaneous and prolonged activation of JNK and p38. These mitogen-activated protein kinases (MAPKs) mediate different effects: JNK is crucial for apoptosis, whereas p38 causes an increase in the p21 level and a concomitant cell cycle arrest. Our study shows that GSTP1-1 plays an important regulatory role in TRAF signaling of osteosarcoma and discloses new features of the action mechanism of NBDHEX that suggest potentially practical consequences of these findings. PMID- 22068641 TI - Mono thiomalonates as thioester enolate equivalents--enantioselective 1,4 addition reactions to nitroolefins under mild conditions. AB - Mono thiomalonates (MTMs) are introduced as thioester enolate equivalents. Asymmetric organocatalyzed conjugate addition reactions to nitroolefins proceed under mild conditions to afford synthetically useful gamma-nitrothioesters with excellent yields and enantioselectivities. PMID- 22068642 TI - Craniofacial reconstruction as a treatment for elevated intracranial pressure. AB - INTRODUCTION: Craniofacial procedures may be needed to address symptomatic intracranial hypertension. The authors review their institutional experience in the treatment of children with symptomatic increased intracranial pressure (ICP) utilizing craniofacial reconstructive procedures. METHODS: The senior authors' (HSM, SRC) craniofacial experience of 222 patients over a 7-year period from 2000 to 2007 at a single institution (Rady Children's Hospital, San Diego) is reviewed. Seventeen patients were identified who were felt to be candidates for craniofacial surgery with symptomatic increased ICP. RESULTS: Patient diagnoses included single-suture craniosynostosis, craniofacial dysostoses, shunt-induced craniostenosis, and shunt-associated intracranial hypertension (slit-ventricle syndrome). Seventeen patients underwent 21 craniofacial procedures. Age at surgery ranged from 3 months to 13 years with a mean of 5 years. Preoperative symptoms and signs included headaches, unexplained irritability, seizures, papilledema, and visual loss. All patients had diagnostic neuroimaging. Seven patients had preoperative invasive ICP measurements. Surgery was deferred on three of these patients based on these measurements. The mean total operative (including anesthetic preparation) and surgical times were 3 h 12 min and 2 h 20 min, respectively. Percentage operative blood loss averaged 11.3%. In six procedures, no transfusions were required. Average hospital stay was 4 days. There was no perioperative mortality or significant surgery associated morbidity. All patients have had postoperative clinical improvement in signs and symptoms of increased ICP. CONCLUSIONS: Using modern diagnostic and surgical techniques, including invasive ICP monitoring, increased intracranial pressure can be successfully managed by an experienced, multidisciplinary, craniofacial team. Our treatment paradigm and operative management scheme is discussed. PMID- 22068643 TI - Eosinophilic enteritis presenting as a perforated duodenal ulcer. PMID- 22068644 TI - Massive mucinous discharge from a fistula caused by intraductal papillary mucinous neoplasm diagnosed by endoscopic ultrasound. PMID- 22068645 TI - A case of propofol dependence after repeated use for endoscopy. PMID- 22068646 TI - Pancreatic cystic neoplasm presenting as a large gastric ulcer. PMID- 22068647 TI - Coil migration into the common bile duct after embolization of a hepatic artery pseudoaneurysm. PMID- 22068648 TI - Endoscopic sphincterotomy using a stabilizer-attached sphincterotome in Billroth II anatomy. PMID- 22068649 TI - Arytenoid dislocation following upper gastrointestinal endoscopy. PMID- 22068650 TI - Gastroparesis following endoscopic submucosal dissection for early gastric cancer. PMID- 22068651 TI - Endoscopic retrieval of a migrated stent after endoscopic ultrasound-guided choledochoduodenostomy. PMID- 22068652 TI - Endoscopic removal of a gastric bezoar consisting of self-expanding spray foam used for insulating window frames. PMID- 22068653 TI - Nodal metastasis after successful endoscopic submucosal dissection for colorectal mucosal cancer. PMID- 22068654 TI - Indoleamine 2,3-dioxygenase expression in human cancers: clinical and immunologic perspectives. AB - Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme with immune regulating activities in many contexts, such as fetal protection, allograft protection, and cancer progression. Clinical trials are currently evaluating IDO inhibition with 1-methyltryptophan in cancer immunotherapy. However, the exact role of tryptophan catabolism by IDO in human cancers remains poorly understood. Here, we review several studies that correlate IDO expression in human cancer samples and tumor-draining lymph nodes, with relevant clinical or immunologic parameters. IDO expression in various histologic cancer types seems to decrease tumor infiltration of immune cells and to increase the proportion of regulatory T lymphocytes in the infiltrate. The impact of IDO on different immune cell infiltration leads to the conclusion that IDO negatively regulates the recruitment of antitumor immune cells. In addition, increased IDO expression correlates with diverse tumor progression parameters and shorter patient survival. In summary, in the vast majority of the reported studies, IDO expression is correlated with a less favorable prognosis. As we may see results from the first clinical trials with 1-methyltryptophan in years to come, this review brings together IDO studies from human studies and aims to help appreciate outcomes from current and future trials. Consequently, IDO inhibition seems a promising approach for cancer immunotherapy. PMID- 22068655 TI - MAGE: the spell is broken. AB - The success of immunotherapy in Hodgkin lymphoma is hampered partly by limited expression of tumor-specific antigens in the malignant cells. One strategy to increase tumor immunogenicity may be to enhance the expression of Hodgkin lymphoma-specific antigens such as MAGE-A4 using epigenetic-modifying drugs in combination with cancer testis antigen-specific immunotherapy. PMID- 22068656 TI - A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in patients with metastatic breast and ovarian cancer. AB - PURPOSE: PANVAC is a recombinant poxviral vaccine that contains transgenes for MUC-1, CEA, and 3 T-cell costimulatory molecules. This study was conducted to obtain preliminary evidence of clinical response in metastatic breast and ovarian cancer patients. EXPERIMENTAL DESIGN: Twenty-six patients were enrolled and given monthly vaccinations. Clinical and immune outcomes were evaluated. RESULTS: These patients were heavily pretreated, with 21 of 26 patients having 3 or more prior chemotherapy regimens. Side effects were largely limited to mild injection-site reactions. For the 12 breast cancer patients enrolled, median time to progression was 2.5 months (1-37+) and median overall survival was 13.7 months. Four patients had stable disease. One patient had a complete response by RECIST and remained on study for 37 months or more, with a significant drop in serum interleukin (IL)-6 and IL-8 by day 71. Another patient with metastatic disease confined to the mediastinum had a 17% reduction in mediastinal mass and was on study for 10 months. Patients with stable or responding disease had fewer prior therapies and lower tumor marker levels than patients with no evidence of response. For the ovarian cancer patients (n = 14), the median time to progression was 2 months (1 6) and median overall survival was 15.0 months. Updated data are presented here for one patient treated with this vaccine in a previous trial, with a time to progression of 38 months. CONCLUSIONS: Some patients who had limited tumor burden with minimal prior chemotherapy seemed to benefit from the vaccine. Further studies to confirm these results are warranted. PMID- 22068657 TI - Tumor-derived autophagosome vaccine: mechanism of cross-presentation and therapeutic efficacy. AB - PURPOSE: We previously reported that autophagy in tumor cells plays a critical role in cross-presentation of tumor antigens and that autophagosomes are efficient antigen carriers for cross-priming of tumor-reactive CD8(+) T cells. Here, we sought to characterize further the autophagosome-enriched vaccine named DRibble (DRiPs-containing blebs), which is derived from tumor cells after inhibition of protein degradation, and to provide insights into the mechanisms responsible for their efficacy as a novel cancer immunotherapy. EXPERIMENTAL DESIGN: DRibbles were characterized by Western blot and light or transmission electron microscopy. The efficiency of cross-presentation mediated by DRibbles was first compared with that of whole-tumor cells and pure proteins. The mechanisms of antigen cross-presentation by DRibbles were analyzed, and the antitumor efficacy of the DRibble vaccine was tested in 3LL Lewis lung tumors and B16F10 melanoma. RESULTS: The DRibbles sequester both long-lived and short-lived proteins, including defective ribosomal products (DRiP), and damage-associated molecular pattern molecules exemplified by HSP90, HSP94, calreticulin, and HMGB1. DRibbles express ligands for CLEC9A, a newly described C-type lectin receptor expressed by a subset of conventional and plasmacytoid dendritic cells (DC), and cross-presentation was partially CLEC9A dependent. Furthermore, this autophagy assisted antigen cross-presentation pathway involved both caveolae- and clathrin mediated endocytosis and endoplasmic reticulum-associated degradation machinery. It depends on proteasome and TAP1, but not lysosome functions of antigen presenting cells. Importantly, DCs loaded with autophagosome-enriched DRibbles can eradicate 3LL Lewis lung tumors and significantly delay the growth of B16F10 melanoma. CONCLUSIONS: These data documented the unique characteristics and potent antitumor efficacy of the autophagosome-based DRibble vaccine. The efficacy of DRibble cancer vaccine will be further tested in clinical trials. PMID- 22068658 TI - Two distinct routes to oral cancer differing in genome instability and risk for cervical node metastasis. AB - PURPOSE: Problems in management of oral cancers or precancers include identification of patients at risk for metastasis, tumor recurrence, and second primary tumors or risk for progression of precancers (dysplasia) to cancer. Thus, the objective of this study was to clarify the role of genomic aberrations in oral cancer progression and metastasis. EXPERIMENTAL DESIGN: The spectrum of copy number alterations in oral dysplasia and squamous cell carcinomas (SCC) was determined by array comparative genomic hybridization. Associations with clinical characteristics were studied and results confirmed in an independent cohort. RESULTS: The presence of one or more of the chromosomal aberrations +3q24-qter, 8pter-p23.1, +8q12-q24.2, and +20 distinguishes a major subgroup (70%-80% of lesions, termed 3q8pq20 subtype) from the remainder (20%-30% of lesions, non 3q8pq20). The 3q8pq20 subtype is associated with chromosomal instability and differential methylation in the most chromosomally unstable tumors. The two subtypes differ significantly in clinical outcome with risk for cervical (neck) lymph node metastasis almost exclusively associated with the 3q8pq20 subtype in two independent oral SCC cohorts. CONCLUSIONS: Two subtypes of oral lesions indicative of at least two pathways for oral cancer development were distinguished that differ in chromosomal instability and risk for metastasis, suggesting that +3q,-8p, +8q, and +20 constitute a biomarker with clinical utility for identifying patients at risk for metastasis. Moreover, although increased numbers of genomic alterations can be harbingers of progression to cancer, dysplastic lesions lacking copy number changes cannot be considered benign as they are potential precursors to non-3q8pq20 locally invasive, yet not metastatic oral SCC. PMID- 22068659 TI - CPTH6, a thiazole derivative, induces histone hypoacetylation and apoptosis in human leukemia cells. AB - PURPOSE: We previously identified novel thiazole derivatives able to reduce histone acetylation and histone acetyltransferase (HAT) activity in yeast. Among these compounds, 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2 yl]hydrazone (CPTH6) has been selected and used throughout this study. EXPERIMENTAL DESIGN: The effect of CPTH6 on histone acetylation, cell viability and differentiation, cell-cycle distribution, and apoptosis in a panel of acute myeloid leukemia and solid tumor cell lines has been evaluated. RESULTS: Here, we showed that CPTH6 leads to an inhibition of Gcn5 and pCAF HAT activity. Moreover, it inhibits H3/H4 histones and alpha-tubulin acetylation of a panel of leukemia cell lines. Concentration- and time-dependent inhibition of cell viability, paralleled by accumulation of cells in the G(0)/G(1) phase and depletion from the S/G(2)M phases, was observed. The role of mitochondrial pathway on CPTH6-induced apoptosis was shown, being a decrease of mitochondrial membrane potential and the release of cytochrome c, from mitochondria to cytosol, induced by CPTH6. Also the involvement of Bcl-2 and Bcl-xL on CPTH6-induced apoptosis was found after overexpression of the two proteins in leukemia cells. Solid tumor cell lines from several origins were shown to be differently sensitive to CPTH6 treatment in terms of cell viability, and a correlation between the inhibitory efficacy on H3/H4 histones acetylation and cytotoxicity was found. Differentiating effect on leukemia and neuroblastoma cell lines was also induced by CPTH6. CONCLUSIONS: These results make CPTH6 a suitable tool for discovery of molecular targets of HAT and, potentially, for the development of new anticancer therapies, which warrants further investigations. PMID- 22068660 TI - Synergistic antitumor activity of anti-CD25 recombinant immunotoxin LMB-2 with chemotherapy. AB - PURPOSE: Although anti-CD25 recombinant immunotoxin LMB-2 is effective against CD25(+) hairy cell leukemia, activity against more aggressive diseases such as adult T-cell leukemia (ATL) is limited by rapid disease progression between treatment cycles. Our goal was to determine in vivo whether rapid growth of CD25(+) tumor is associated with high levels of tumor interstitial soluble CD25 (sCD25) and whether chemotherapy can reduce tumor sCD25 and synergize with LMB-2. EXPERIMENTAL DESIGN: Tumor xenografts expressing human CD25 were grown in mice, which were then treated with LMB-2 and chemotherapy either alone or in combination, and sCD25 level and antitumor activity were measured. RESULTS: CD25(+) human xenografts growing rapidly in nude mice had intratumoral sCD25 at levels that were between 21- and 2,200 (median 118)-fold higher than in serum, indicating that interstitial sCD25 interacts with LMB-2 in tumors. Intratumoral sCD25 levels were in the range 21 to 157 (median 54) ng/mL without treatment and 0.95 to 6.1 (median 2.6) ng/mL (P < 0.0001) 1 day after gemcitabine administration. CD25(+) xenografts that were too large to regress with LMB-2 alone were minimally responsive to gemcitabine alone but completely regressed with the combination. Ex vivo, different ratios of gemcitabine and LMB-2 were cytotoxic to the CD25(+) tumor cells in an additive, but not synergistic, manner. CONCLUSIONS: Gemcitabine is synergistic with LMB-2 in vivo unrelated to improved cytotoxicity. Synergism, therefore, appears to be related to improved distribution of LMB-2 to CD25(+) tumors, and is preceded by decreased sCD25 within the tumor because of chemotherapy. To test the concept of combined treatment clinically, patients with relapsed/refractory ATL are being treated with fludarabine plus cyclophosphamide before LMB-2. PMID- 22068662 TI - Facile synthesis of hierarchical core-shell Fe3O4@MgAl-LDH@Au as magnetically recyclable catalysts for catalytic oxidation of alcohols. AB - A novel core-shell structural Fe(3)O(4)@MgAl-LDH@Au nanocatalyst was simply synthesized via supporting Au nanoparticles on the MgAl-LDH surface of Fe(3)O(4)@MgAl-LDH nanospheres. The catalyst exhibited excellent activity for the oxidation of 1-phenylethanol, and can be effectively recovered by using an external magnetic field. PMID- 22068661 TI - Modeling the transcriptional consequences of epidermal growth factor receptor ablation in Ras-initiated squamous cancer. AB - PURPOSE: Epidermal growth factor receptor (EGFR)-targeted therapy is in clinical use to treat squamous cell carcinoma of the head and neck and other cancers of lining epithelium. RAS mutations in these tumors are a negative prognostic factor for response, and skin inflammation is an adverse reaction to therapy. We investigated transcriptional and biochemical changes that could account for the confounding effects of RAS activation and inflammation in a squamous tissue. EXPERIMENTAL DESIGN: We carried out gene expression profiling on oncogenic Ras transformed and wild-type mouse and human keratinocytes with EGFR ablated chronically by genetic deletion or acutely by drug treatment and followed leads provided by pathway analysis with biochemical studies. RESULTS: We identified a 25-gene signature specific to the Ras-EGFR ablation interaction and a distinct 19 gene EGFR ablation signature on normal keratinocytes. EGFR ablation in the context of wild-type Ras reduces ontologies favoring cell-cycle control and transcription, whereas oncogenic Ras enriches ontologies for ion channels and membrane transporters, particularly focused on calcium homeostasis. Ontologies between chronic EGFR ablation and acute pharmacologic ablation were unique, both with and without Ras activation. p38alpha is activated in response to abrogation of EGFR signaling under conditions of Ras activation in both mouse and human keratinocytes and in RAS-transformed tumor orthografts of EGFR-ablated mouse keratinocytes. EGFR ablation in the absence of oncogenic Ras revealed Erk and interleukin-1beta-related pathways. CONCLUSION: These findings reveal unrecognized interactions between Ras and EGFR signaling in squamous tumor cells that could influence the therapeutic response to EGFR ablation therapy. PMID- 22068663 TI - Diagnostic accuracy of probe-based confocal laser endomicroscopy and narrow band imaging for small colorectal polyps: a feasibility study. AB - OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) allows real-time in vivo microscopic imaging of tissue. Narrow band imaging (NBI) can also classify colorectal lesions. Both systems may allow accurate optical diagnosis of small (6 9 mm) and diminutive (1-5 mm) polyps without histopathology. This study assesses the accuracy of pCLE and NBI for prediction of histology. METHODS: Participants underwent high-definition colonoscopy. The surface pit pattern of all polyps (1-9 mm) was determined in vivo using NBI. Confocal videos were obtained after administration of IV fluorescein. Recorded videos were subsequently analyzed offline, blinded to endoscopic characteristics, and histopathology. Confocal images were classified as neoplastic and non-neoplastic according to the Miami classification system. RESULTS: A total of 130 polyps (58 neoplastic, 72 non neoplastic, mean size 4.6 mm) from 65 patients were assessed. Assuming histopathology as gold standard, pCLE had higher sensitivity than NBI (86% vs. 64%, P=0.008), with lower specificity (78% vs. 92%, p=0.027) and similar overall accuracy (82% vs. 79%, P=0.59). When 65 high-confidence cases were analyzed (polyps diagnosed identically with pCLE and NBI and with high-quality confocal videos), sensitivity and specificity were 94 and 97%. CONCLUSIONS: pCLE demonstrated higher sensitivity in predicting histology of small polyps compared with NBI, whereas NBI had higher specificity. When used in combination, the accuracy of pCLE and NBI was extremely high, approaching the accuracy of histopathology. Together, they may reduce the need for histological examination. However, further studies are warranted to evaluate the role of these techniques, especially in the population-based colon cancer screening. PMID- 22068664 TI - IBS patients show frequent fluctuations between loose/watery and hard/lumpy stools: implications for treatment. AB - OBJECTIVES: The objectives of this study were to determine how variable stool consistency is in patients with irritable bowel syndrome (IBS) and to assess the relationship between stool consistency and gastrointestinal symptoms. METHODS: Individuals with a physician diagnosis of IBS were recruited by advertisement. Enrollment questionnaires included the Rome III Diagnostic Questionnaire and IBS Symptom Severity Scale. Then, 185 patients meeting the Rome criteria for IBS rated the consistency (using the Bristol Stool Scale) of each bowel movement (BM) for 90 days and whether the BM was accompanied by pain, urgency, or soiling. Each night, they transferred BM ratings from a paper diary to an internet form and also reported the average daily intensity of abdominal pain, bloating, bowel habit dissatisfaction, and life interference of bowel symptoms. Only the longest sequence of consecutive days of diary data was used in the analysis (average of 73 days). RESULTS: Patients were 89% females with average age 36.6 years. Among the patients, 78% had both loose/watery and hard/lumpy stools; the average was three fluctuations between these extremes per month. The proportion of loose/watery stools correlated r=0.78 between the first and second months and the proportion of hard/lumpy stools correlated r=0.85 between months. Loose/watery stools were associated with more BM-related pain, urgency, and soiling than hard/lumpy or normal stools; however, IBS-C patients had significantly more BM unrelated abdominal pain, bloating, dissatisfaction with bowel habits, and life interference than IBS-D patients. Questionnaires overestimated the frequency of abnormal stool consistency and gastrointestinal symptoms compared with diaries. CONCLUSIONS: Stool consistency varies greatly within individuals. However, stool patterns are stable within an individual from month to month. The paradoxical findings of greater symptom severity after individual loose/watery BMs vs. greater overall symptom severity in IBS-C implies different physiological mechanisms for symptoms in constipation compared with diarrhea. Daily symptom monitoring is more sensitive and reliable than a questionnaire. PMID- 22068665 TI - Peroral endoscopic myotomy for the treatment of achalasia: a prospective single center study. AB - OBJECTIVES: Endoscopic balloon dilatation and laparoscopic myotomy are established treatments for achalasia. Recently, a new endoscopic technique for complete myotomy was described. Herein, we report the results of the first prospective trial of peroral endoscopic myotomy (POEM) in Europe. METHODS: POEM was performed under general anesthesia in 16 patients (male:female (12:4), mean age 45 years, range 26-76). The primary outcome was symptom relief at 3 months, defined as an Eckhard score <=3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM. RESULTS: A 3-month follow-up was completed for all patients. Treatment success (Eckhard score <=3) was achieved in 94% of cases (mean score pre- vs. post-treatment (8.8 vs. 1.4); P<0.001). Mean LES pressure was 27.2 mm Hg pre-treatment and 11.8 mm Hg post treatment (P<0.001). No patient developed symptoms of gastro-esophageal reflux after treatment, but one patient was found to have an erosive lesion (LA grade A) on follow-up esophagogastroduodenoscopy. No patient required medication with proton pump inhibitors or antacids after POEM. CONCLUSIONS: POEM is a promising new treatment for achalasia resulting in short-term symptom relief in >90% of cases. Studies evaluating long-term efficacy and comparing POEM with established treatments have been initiated. PMID- 22068666 TI - The spectrum of sclerosing cholangitis and the relevance of IgG4 elevations in routine practice. AB - OBJECTIVES: American Association for the Study of Liver Diseases (AASLD) guidance recommends measurement of IgG4 in patients with sclerosing cholangitis (SC). The objective of this study was to evaluate this by analyzing our SC practice. METHODS: Characteristics were collected on 168 patients with radiological or biopsy proven SC; IgG4 was measured and magnetic resonance cholangiopancreatography studies were reviewed. RESULTS: In all, 49% of patients were females and 55% had inflammatory bowel disease. Large duct disease was present in 63%, small duct disease in 8%, overlap with AIH in 11%, and secondary SC in 18%. Secondary etiologies included autoimmune pancreatitis (AIP) (8%), intra-hepatic cholelithiasis (3%), portal vein thrombosis (2%), and neonatal Kasai (2%). In all, 101 patients had sufficient radiology and serology for re evaluation. IgG4 was elevated (>104 mg/dl) in 22% of patients. This was associated with male gender (73%; P=0.016), a past history of pancreatitis (27% vs. 5%; P=0.007), a higher alkaline phosphatase (ALP) value, median 338.5 U/l vs. 160 (P=0.005), and a higher primary sclerosing cholangitis (PSC) Mayo risk score, mean 0.6 vs. -0.2 (P=0.0008). Prior biliary intervention was more likely (36 vs. 13%; P=0.023), while abnormal pancreatic imaging was noted in 15%, more frequently if IgG4 was elevated (40 vs. 8%; P=0.0007). After excluding those with pancreatic disease on magnetic resonance imaging, 14 patients had elevated IgG4. This group had higher ALP 379 U/l vs. 155.5 (P=0.0006), aspartate aminotransferase (AST) 72.5 U/l vs. 34 (P=0.0005), alanine aminotransferase (ALT) 90.5 U/l vs. 36 (P=0.004), and PSC Mayo risk score values 0.4 vs. -0.2 (P=0.017). CONCLUSIONS: SC is a heterogeneous liver injury. IgG4 testing may be clinically important in all patients, since it appears to identify a distinct patient population, more so than just those with AIP. PMID- 22068667 TI - The extract of Cordyceps sinensis inhibited airway inflammation by blocking NF kappaB activity. AB - Aiming the extract of Cordyceps sinensis significantly inhibits airway inflammation, airway hyperresponsiveness, and the infiltration of eosinophils in the airway of rats and may be related to the modulation of T helper (Th)1 and Th2 cells functions. The mechanisms of C. sinensis involved in modulation of suppression inflammation are not yet determined. In this study, the mechanism involved in the extract of C. sinensis-C.S.3-modulated suppression of inflammation was investigated in vivo and in vitro systems. The results showed that C.S.3 reduced airway inflammation in ovalbumin-induced allergic mice. Furthermore, we found C.S.3 could decrease extracellular signal-regulated kinase 1/2 signaling pathway to suppress activity of nuclear factor-kappaB in lung cells and cultured airway smooth muscle cells. Conclusion C.S.3 may provide clinical applications for asthma in the future. PMID- 22068668 TI - Static and Dynamic Electrocardiographic Patterns Preceding Torsades de Pointes in the Acquired and Congenital Long QT Syndrome. AB - The arrhythmogenic mechanisms involved in the triggering of the polymorphic ventricular tachycardia called torsades de pointes (TdPs) remains to be elucidated. In this work, we investigated the static and dynamic profiles of the repolarization interval from the surface electrocardiogram recorded in healthy individuals and in cardiac patients with TdPs. We implemented this analysis just prior to the arrhythmia onset and we computed the delta values based on baseline periods (1 hour prior to event). We measured QT/QTc prolongation, QT variability, ventricular ectopic beats (VPBs) frequency, T-wave amplitude, T-peak to T-end interval, and T-wave complexcity. The analysis of these parameters in reference to baseline revealed 1) an increased QTc variability, 2) the presence of VPCs, and 3) the profound changes in T-loop morphology in patients developing TdPs. PMID- 22068669 TI - Surgical repair for rupture of a chronic traumatic thoracic aneurysm 14 years after injury: report of a case. AB - Traumatic thoracic aortic injury is a lethal condition. Because its mortality rate is extremely high in the acute phase, these patients rarely survive long enough for a chronic aneurysm to develop. We herein report a case of surgical repair for a ruptured chronic traumatic thoracic aneurysm. A 32-year-old man, who had been involved in a traffic accident 14 years earlier, was diagnosed with a rupture of a chronic traumatic thoracic aneurysm. Preoperative computed tomography showed that the ruptured aneurysm arose from the aortic isthmus and was accompanied by multiple daughter lesions. He underwent an aorta graft replacement with reconstruction of the left subclavian artery using both a median sternotomy and a left thoracotomy. The surgery was successful and the postoperative course was uneventful. Chronic traumatic thoracic aneurysm is usually a single lesion, and cases with daughter aneurysms have rarely been reported. We include a review of the previous literature and also discuss the etiology of this condition. PMID- 22068670 TI - Clinical evaluation of leukocyte filtration as an alternative anti-inflammatory strategy to aprotinin in high-risk patients undergoing coronary revascularization. AB - PURPOSE: The use of aprotinin in cardiac surgery is associated with overriding safety concerns. Therefore, there is increased research on alternatives. This study investigated the relative benefits of strategic leukofiltration on polymer coated extracorporeal circuits (ECC), aprotinin, and combined therapy in high risk patients. METHODS: Eight hundred and seventy-five patients (EuroSCORE 6+) undergoing coronary revascularization over a 4-year period were prospectively randomized to one of four perfusion protocols: Group 1: polymethoxyethylacrylate (PMEA)-coated circuits + leukocyte filters (n = 214); Group 2: uncoated ECC + full Hammersmith aprotinin (n = 212); Group 3: PMEA-coated ECC + leukofilters + full Hammersmith aprotinin (n = 199); and Group 4: control-no treatment (n = 250). Blood samples were collected at times T1: following the induction of anesthesia; T2: following heparin administration; T3: 15 min after cardiopulmonary bypass (CPB); T4: before cessation of CPB; T5: 15 min after protamine reversal; and T6: in the intensive care unit. RESULTS: The serum interleukin-2 levels were significantly lower at T3, T4, and T5 in all study groups. C3a levels were significantly lower at T3. Creatine kinase MB and lactate levels demonstrated well-preserved myocardia in both leukofiltration groups (P < 0.05). Neutrophil CD11b/CD18 levels were significantly lower for all study groups. Postoperative bleeding and respiratory support time were lower in all study groups. CONCLUSION: Leukofiltration on coated circuits significantly reduced bleeding and inflammatory response related to CPB with no adverse effects, and may be a possible alternative to pharmacological intervention. PMID- 22068671 TI - Kampo medicine "Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats. AB - PURPOSE: The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. METHODS: Twenty four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. RESULTS: Interleukin (IL)-1beta, IL 12, interferon (IFN)-gamma, and tumor necrosis factor-alpha expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1beta and IFN-gamma expression was improved significantly by DKT (P < 0.05). The number and height of jejuna villi, injury score, and apoptosis index in the CPT-11 group were improved significantly by DKT (P < 0.05). CONCLUSIONS: DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity. PMID- 22068672 TI - Pancreaticoduodenectomy with resection of the splenic artery and splenectomy for pancreatic double cancers after total gastrectomy. Preservation of the pancreatic function via the blood supply from the posterior epiploic artery: report of a case. AB - The patient was a 56-year-old man who had previously undergone a total gastrectomy without splenectomy, and was diagnosed with pancreatic head and body cancers and primary solitary lung cancer. The pancreas body tumor invaded the origin of the splenic artery, and if the origin of the splenic artery were resected there would be no blood flow to the pancreas tail, resulting in a need for total pancreatectomy. However, we focused on the posterior epiploic artery (PEA), which is a less well known blood supply from the mesocolon to pancreatic body and tail, and planned to preserve the pancreatic tail as long as the resected margin of the pancreas was not malignant, considering his limited life expectancy. We performed a pancreaticoduodenectomy with resection of the origin of the splenic artery and splenectomy, preserving the pancreatic tail and PEA. The patient has been free from insulin therapy for blood sugar control, and has been well for 10 months after the surgery. PMID- 22068673 TI - Prosthetic repair of an incarcerated groin hernia with small intestinal resection. AB - PURPOSE: No consensus has been reached on the use of prostheses in a potentially infected operating field. In this study, we evaluated the validity of a mesh prosthesis for the repair of incarcerated groin hernias with intestinal resection. METHODS: Twenty-seven patients underwent operations for correction of incarcerated groin hernias with small intestinal resection at our hospital between January 2000 and March 2010. The patients were divided into two groups: those who underwent repair with a prosthetic mesh and those who underwent primary hernia repair. Patients with intestinal perforations, abscess formations, panperitonitis, and those who required colon resections were excluded. The length of the operation, blood loss, and incidences of surgical site infection, postoperative ileus, and recurrence were evaluated in each group. RESULTS: Of the 27 patients studied, 10 (37%) underwent tension-free repair with a mesh, and 17 (63%) underwent primary hernia repair. Although the patients who underwent primary hernia repair were significantly older than the patients who underwent mesh repair (P = 0.015), no statistically significant differences in morbidity, including surgical site infection, or mortality, were identified. CONCLUSION: Strangulated inguinal hernias cannot be considered a contraindication to the use of a prosthetic mesh even in cases requiring small-intestinal resection. PMID- 22068674 TI - Single-site laparoscopic herniorrhaphy using needle instruments for inguinal hernias in children: a novel technique. AB - We describe our new technique for laparoscopic herniorrhaphy with subumbilical single-site access to treat inguinal hernias in children. First, we inserted a transparent 3-mm trocar and a 2-mm minitrocar at the umbilicus. We then inserted a 3-mm 45 degrees camera through the 3-mm trocar and needle-grasping forceps through the 2-mm trocar. We closed the hernia defect by using a 19-gauge hooked injection needle with a nonabsorbable suture. We treated 11 consecutive female children with inguinal hernia using this operation. The mean operating time was 26.7 min (range 21-36 min) and the procedure was technically successful, without the need for additional trocars, in all 11 patients. There were no intraoperative complications and all the patients were discharged on the same day after the surgery. Single-site laparoscopic herniorrhaphy using needle instruments is feasible and seems to be safe. Further studies are required to determine whether this approach would benefit patient compared with standard laparoscopic herniorrhaphy. PMID- 22068675 TI - Effect of intra-abdominal absorbable sutures on surgical site infection. AB - PURPOSE: To establish whether the rates of surgical site infection (SSI) in gastrointestinal surgery are affected by the type of intra-abdominal suturing: sutureless, absorbable material (polyglactin: Vicryl), and silk. METHODS: We conducted SSI surveillance prospectively at 25 hospitals. RESULTS: The overall SSI rate was 14.4% (130/903). The SSI rates in the sutureless, Vicryl, and silk groups were 4.8, 14.8, and 16.4%, respectively, without significant differences among the groups. In colorectal surgery, the SSI rate in the Vicryl group was 13.9%, which was significantly lower than that of the silk group (22.4%; P = 0.034). The incidence of deeper SSIs in the Vicryl group, including deep incisional and organ/space SSIs, was significantly lower than that in the silk group (P = 0.04). The SSI rates did not differ among the suture types overall, in gastric surgery, or in appendectomy. CONCLUSION: Using intra-abdominal absorbable sutures instead of silk sutures may reduce the risk of SSI, but only in colorectal surgery. PMID- 22068676 TI - Expanding the applications of microvascular surgical techniques to digestive surgeries: a technical review. AB - In living donor liver transplantation (LDLT), it is considered safer to reconstruct hepatic arteries (HAs) under a microscope than under conventional loupe magnification, because graft HA stumps are generally thin and short with an average diameter of approximately 2 mm. We first applied microvascular surgical techniques to HA reconstruction for LDLT in 1996. In most cases, we use a disposable double-clip to secure the graft and recipient arteries, and interrupted 8-0 nonabsorbable monofilament sutures. We next started performing resection and reconstruction of the right HA in a surgery for hilar cholangioma using the same technique as in LDLT. Lately, we have started applying microvascular surgical techniques to various digestive surgeries; namely, supercharge and superdrainage in esophageal surgery, vascular reconstruction in free jejunal interposition grafts for cervical esophageal cancer, resection and reconstruction of spontaneous HA aneurysms, jejunal artery reconstruction for spontaneous superior mesenteric artery dissections, and so forth. Mastering this technique is time consuming. However, once a surgeon masters the technique it has almost unlimited applications, and most vital vessels can be safely reconstructed using this method. We herein provide a technical review of the application of microvascular surgical techniques for various digestive surgeries. PMID- 22068677 TI - Interleukin 6 and interleukin 8 play important roles in systemic inflammatory response syndrome of meconium peritonitis. AB - PURPOSE: Meconium peritonitis is caused by an intestinal perforation that may occur in the fetus, followed by severe chemical peritonitis, resulting in high morbidity. METHODS: We have experienced six patients with meconium peritonitis. Cystic drainage was performed soon after birth for all patients. We investigated the concentrations of several cytokines and a chemokine (interleukin 8) in the ascites from the six patients with meconium peritonitis. In two patients we also measured the serum cytokines and chemokine level just after birth. RESULTS: Interleukin 6 and interleukin 8 concentrations were very high in the cyst or ascites just after birth. In the serum taken from two patients, the levels of interleukin 6 and interleukin 8 were also high. In five patients who underwent drainage of cysts after birth, systemic inflammation could not be completely suppressed before curative surgery. CONCLUSIONS: Interleukin 6 and interleukin 8 play important roles in the inflammatory response syndrome associated with meconium peritonitis, and drainage of cystic fluid did not completely suppress this inflammation. To lessen the high morbidity of meconium peritonitis, efforts should be made to suppress the inflammatory response using new treatment strategies, such as administration of steroids or anti-cytokine therapy to supplement cystic drainage. PMID- 22068678 TI - Mediastinoscopy-assisted esophagectomy for esophageal cancer in patients with serious comorbidities. AB - PURPOSE: We evaluated the results of mediastinoscopy-assisted esophagectomy (MAE), performed for esophageal cancer patients with comorbidities, versus those of thoracoscopic esophagectomy (TSE), performed for esophageal patients with or without comorbidities. METHODS: Among 153 patients who underwent esophageal cancer surgery at our hospital, 17 (11.1%) underwent MAE and 37 (24.2%) underwent TSE. RESULTS: Many of the MAE group patients had pulmonary (P < 0.001), cardiovascular (P = 0.031), or hepatic (P = 0.0029) diseases preoperatively, and these comorbidities frequently overlapped (P < 0.0001). The %VC and FEV(1)/FVC were lower (P = 0.0099 and P = 0.0057, respectively), and the ICG-R15 and serum level of HbA1c were higher (P = 0.0014 and P = 0.043, respectively) in the MAE group. There were no differences in postoperative complications or in the modified Clavien classification between the groups. There was no mortality in either group. After MAE, 5 (29.4%) patients died of other diseases. The 5-year overall survival rate after MAE was poorer than that after TSE (56.1 vs. 71.8%), but the 5-year cause-specific survival rates were similar in the two groups. CONCLUSIONS: MAE is feasible for esophageal cancer patients with serious comorbidities and may decrease morbidity and mortality. PMID- 22068679 TI - Pulmonary pleomorphic carcinoma producing granulocyte-macrophage colony stimulating factor: report of a case. AB - We report a case of lung cancer producing granulocyte-macrophage colony stimulating factor (GM-CSF). The patient, a 55-year-old woman, was found to have leukocytosis (leukocytes 28.8 * 10(3)/mm3) with eosinophilia (eosinophils 24.5%) without any evidence of infection or allergy. The serum concentration of GM-CSF was elevated to 44 pg/ml (normal range <2.0 pg/ml), which might have induced the leukocytosis and eosinophilia. We performed left pneumonectomy and diagnosed a pleomorphic carcinoma with p-T2bN0M0, based on histological examination of the resected tumor. Immunohistochemical examination revealed GM-CSF. The serum level of GM-CSF decreased to within the normal range 8 days after surgery. At the time of writing, 16 months after the surgery, she was alive without disease. To our knowledge, this represents the first case report of a GM-CSF-producing tumor effectively treated by surgical resection. PMID- 22068680 TI - Impact of microvessel density on lymph node metastasis and survival after curative resection of pancreatic cancer. AB - PURPOSE: The roles of angiogenesis and the most prominent angiogenic vascular endothelial growth factor (VEGF) in diseases of the pancreas remain controversial. We compared microvessel density (MVD) and VEGF status in normal pancreatic, chronic pancreatic, and pancreatic cancer (PC) tissues to establish their prognostic relevance. METHODS: Eighty samples of PC tissue, 32 samples of normal pancreatic tissue, and 20 samples of chronic pancreatitis (cP) tissue were immunostained with monoclonal anti-CD31 and polyclonal anti-VEGF antibody. The MVD was correlated with clinicopathological features and survival. RESULTS: Microvessel density was higher in PC than in cP (P < 0.001). Residual tumor status was highly predictive for survival (P < 0.001). After stratification for residual tumor status, we identified lymph node metastasis (LNM) in more than two lymph nodes (P < 0.04) and high MVD (P < 0.03) as risk factors for mortality. Multivariate analysis revealed only a high MVD (P = 0.03, odds ratio 0.441, 95% confidence interval 0.211-0.821) as an independent predictor of poor survival. Vascular endothelial growth factor was found over stromal cells in cP and over ductal adenocarcinoma cells in PC. Vascular endothelial growth factor expression status was not predictive of survival (P < 0.07). CONCLUSION: This study confirms the role of angiogenesis in PC and identifies MVD as an independent prognostic factor in patients with curatively resected PC. PMID- 22068681 TI - Granulomatous mastitis: is it an autoimmune disease? Diagnostic and therapeutic dilemmas. AB - PURPOSE: Granulomatous mastitis (GM) is a rare benign inflammatory breast disease. The clinical presentation of granulomatous mastitis usually mimics malignancy or infection. The aim of this study was to review the clinical and diagnostic features of GM and discuss the medical and surgical treatment of our series of eight GM patients. METHODS: Between 2008 and 2010, eight patients were diagnosed with GM and underwent surgery. Patients were evaluated clinically and radiologically. The diagnosis of GM was confirmed in all cases by core needle or excisional biopsies. Serological tests were performed for rheumatoid factor (RF), antinuclear antibody (ANA), and anti-double-stranded DNA (anti-dsDNA). RESULTS: The mean patient age was 37 years. Common presenting symptoms were a hard mass, pain, inflamed hyperemic skin, and sinus formation. Serological tests for RF were positive in 6 patients, and ANA and anti-dsDNA antibodies were detected in 2 patients. All patients underwent antibiotic therapy before surgery, and were treated with wide surgical excision with negative margins. Methylprednisolone (16 mg/day for 3 months) therapy was used in 3 patients (all RF and 2 ANA/anti-dsDNA positive) following a wide excisional biopsy after a postoperative recurrence mimicking skin lesions was seen. These patients responded well to steroid therapy. CONCLUSIONS: The diagnosis of GM should be made carefully to avoid a misdiagnosis. Steroid therapy should be considered based on the idea that this is an autoimmune disease. PMID- 22068682 TI - Electrochemical performance of annealed cobalt-benzotriazole/CNTs catalysts towards the oxygen reduction reaction. AB - One of the major limitations yet to the global implementation of polymer electrolyte membrane fuel cells (PEMFCs) is the cathode catalyst. The development of efficient platinum-free catalysts is the key issue to solve the problem of slow kinetics of the oxygen reduction reaction (ORR) and high cost. We report a promising catalyst for ORR prepared through the annealing treatment under inert conditions of the cobalt-benzotriazole (Co-BTA) complex supported on carbon nanotubes (CNTs). The N-rich benzotriazole precursor was chosen based on its ability to complex Co(II) ions and generate under annealing highly reactive radicals able to tune the physicochemical properties of CNTs. X-Ray photoelectron spectroscopy (XPS) was used to follow the surface structure changes and highlight the active electrocatalytic sites towards the ORR. To achieve further evaluation of the catalysts in acidic medium, voltamperometry, rotating disk electrode (RDE), rotating ring-disk electrode (RRDE) and half-cell measurements were performed. The resulting catalysts (Co/N/CNTs) all show catalytic activity towards the ORR, the most active one resulting from annealing at 700 degrees C. The overall electron transfer number for the catalyzed ORR was determined to be ~3.7 with no change upon the catalyst loading, suggesting that the ORR was dominated by a 4e(-) transfer process. The results indicate a promising alternative cathode catalyst for ORR in fuel cells, although its performance is still lower (overpotential around 110 mV evaluated by RDE and RRDE) than the reference Pt/C catalyst. PMID- 22068684 TI - Three cases of pneumatosis intestinalis presenting in autoimmune diseases. AB - Pneumatosis intestinalis (PI) is a comparatively rare disease characterized by the presence of intramural gas in the gastrointestinal tract. PI is known to be associated with several clinical conditions, such as pulmonary diseases, gastrointestinal diseases, and traumatic injury, as well as autoimmune disorders. In particular, PI is commonly seen in systemic sclerosis (SSc) but rarely in systemic lupus erythematosus and dermatomyositis (DM). In this report, we present three cases of PI presenting in autoimmune diseases, including DM, Sjogren's syndrome, and limited SSc, and further discuss its background characteristics. PMID- 22068683 TI - Early prediction of instability of Chinese hamster ovary cell lines expressing recombinant antibodies and antibody-fusion proteins. AB - One of the most important criteria for the successful manufacture of a therapeutic protein (e.g., an antibody) is to develop a mammalian cell line that maintains stability of production. Problems with process yield, lack of effective use of costly resources, and a possible delay in obtaining regulatory approval of the product may ensue otherwise. Therefore the stability of expression in a number of Chinese hamster ovary (CHO) derived production cell lines that were isolated using the glutamine synthetase (GS) selection system was investigated by defining a culture as unstable if the titer (which is a measure of productivity) of a cell line expressing an antibody or antibody-fusion protein declined by 20 30% or more as it underwent 55 population doublings. Using this criterion, a significant proportion of the GS-selected CHO production cell lines were observed to be unstable. Reduced antibody titers correlated with the gradual appearance of a secondary, less productive population of cells as detected with flow cytometric analysis of intracellular antibody content. Where tested, it was observed that the secondary population arose spontaneously from the parental population following multiple passages, which suggested inherent clonal instability. Moreover, the frequency of unstable clones decreased significantly if the host cell line from which the candidate production cell lines were derived was apoptotic-resistant. This data suggested that unstable cell lines were more prone to apoptosis, which was confirmed by the fact that unstable cell lines had higher levels of Annexin V and caspase 3 activities. This knowledge has been used to develop screening protocols that identify unstable CHO production cell lines at an early stage of the cell line development process, potentially reducing the cost of biotherapeutic development. PMID- 22068685 TI - Simultaneous in vivo RP-HPLC-DAD quantification of multiple-component and drug drug interaction by pharmacokinetics, using 6,7-dimethylesculetin, geniposide and rhein as examples. AB - Increasing evidence has demonstrated that multidrug combinations could amplify the therapeutic efficacies of each agent. Interestingly, the pharmacological effect of traditional Chinese medicine (TCM) is usually attributed to the drug interaction property (synergism) of multiple active constituents. Pharmacokinetics is a useful means of evaluating the drug interactions of major active compounds in TCM. A simple, sensitive and reliable RP-HPLC-DAD method has been developed to simultaneously quantify 6,7-dimethylesculetin (D), geniposide (G) and rhein (R), which are the active ingredients in Yin-Chen-Hao-Tang (YCHT), performing drug-interaction pharmacokinetics studies in vivo. Plasma samples were prepared using methanolic precipitation, a filtration step, and then injection of the methanolic extract onto a Nova-Pak C18 Guard-PakTM guard column with a gradient mobile phase. Triple-wavelength diode array detection was set at lambda(max) values of 343 nm for D, 241 nm for the G, and 259 nm for R. Our results successfully demonstrate that this method has excellent and satisfactory selectivity, sensitivity, linearity, precision, accuracy and recovery. In healthy rats, the estimated pharmacokinetic parameters (i.e. C(max) , AUC and Cl) of D, G and R, when administered with COC (a combination of D, G and R), were C(max) 16.05 mg/L, AUC 108.96 mg h/L and Cl 0.36 L/h for D; C(max) 9.35 mg/L, AUC 64.71 mg h/L and Cl 0.88 L/h for G; and C(max) 14.18 mg/L, AUC 57.98 mg h/L and Cl 1.77 L/h for R. Here, we report that the COC combination could significantly increase the plasma level and slow the elimination rate compared with any one or two of the three individual compounds, which may indicate a drug-drug interaction. PMID- 22068686 TI - A return to basics, a focus on the future. PMID- 22068687 TI - Effect of bismuth breast shielding on radiation dose and image quality in coronary CT angiography. AB - BACKGROUND: Coronary computed tomographic angiography (CCTA) is associated with high radiation dose to the female breasts. Bismuth breast shielding offers the potential to significantly reduce dose to the breasts and nearby organs, but the magnitude of this reduction and its impact on image quality and radiation dose have not been evaluated. METHODS: Radiation doses from CCTA to critical organs were determined using metal-oxide-semiconductor field-effect transistors positioned in a customized anthropomorphic whole-body dosimetry verification phantom. Image noise and signal were measured in regions of interest (ROIs) including the coronary arteries. RESULTS: With bismuth shielding, breast radiation dose was reduced 46%-57% depending on breast size and scanning technique, with more moderate dose reduction to the heart, lungs, and esophagus. However, shielding significantly decreased image signal (by 14.6 HU) and contrast (by 28.4 HU), modestly but significantly increased image noise in ROIs in locations of coronary arteries, and decreased contrast-to-noise ratio by 20.9%. CONCLUSIONS: While bismuth breast shielding can significantly decrease radiation dose to critical organs, it is associated with an increase in image noise, decrease in contrast-to-noise, and changes tissue attenuation characteristics in the location of the coronary arteries. PMID- 22068688 TI - Photoprotective effects of a formulation containing tannase-converted green tea extract against UVB-induced oxidative stress in hairless mice. AB - Ultraviolet B (UVB) irradiation may induce the acceleration of skin aging. The purpose of this study was to develop an effective formulation containing tannase converted green tea extract (FTGE) to inhibit UVB-induced oxidative damage. Significant (p<0.05) prevention of the reduced form of glutathione (GSH) depletion was observed in mice treated with FTGE. The hydrogen peroxide levels of mice treated with FTGE were similar to those of UVB non-irradiated mice. No significant difference was observed between No UVB control and FTGE mice. Also, mice treated with FTGE had significant (p<0.05) decreases in thiobarbituric acid reactive substance levels by lipid peroxidation compared with No UVB control mice. Our data suggest that this formulation may be effective in protecting skin from UVB photodamage. PMID- 22068689 TI - Discrimination of A1555G and C1494T point mutations in the mitochondrial 12S rRNA gene by on/off switch. AB - The objective of this study was to apply the "on/off" switch consisting of 3' phosphorothioate-modified allele specific primers and exo(+) polymerase in single base discrimination of A1555G and C1494T mutations in the highly conserved sites of the mitochondrial 12S rRNA. The two point mutations are the hotspot mutations associated with either aminoglycoside antibiotics induced deafness or inherited nonsyndromic hearing loss. The PCR products of mitochondrial DNA (mtDNA) 12S rRNA gene were inserted into the pMD19-T vector for transformation into Escherichia coli JM109 competent cells for preparing wild-type pMD19-T/mt vector. Inverse PCR was carried out for mtDNA 12S rRNA gene C1494T and A1555G mutagenesis and DpnI endonuclease degradating methylated pMD19-T/mt vector existing in the inverse PCR products was carried out to construct the mutation-type pMD19-T/mtM vector. These constructed vectors were confirmed by DNA sequencing. Allelic specific primers targeting wild-type and mutation-type templates were designed with 3' terminal phosphorothioate modification. Two-directional primer extension was performed using Pfu polymerases. Amplified by exo(+) polymerase, allelic specific primers perfectly matching wild-type allele were extended while no products were produced from primers targeting point-mutated deafness-related allele. Similarly, allelic specific primers perfectly matching point-mutated deafness-related mutation-type allele were extended and no products were yielded from primers targeting wild type allele. No specific product was observed in the primer extension reaction mediated by on/off switch in screening the mtDNA 12S rRNA gene harboring either C1494T or A1555G mutation in 40 healthy volunteers tested. These data suggest that the "off switch" mediated by exo(+) polymerase is highly reliable in the diagnosis of monogenic diseases and the novel "on/off" switch has enormous applications in systematic and extended screening of the12S rRNA gene A1555G and C1494T mutations. The established assay can be widely used not only for hearing loss patients but also for normal subjects before the use of aminoglycoside antibiotics. PMID- 22068690 TI - Kinetics of ergothioneine inhibition of mushroom tyrosinase. AB - The native amino acid ergothioneine, a thiourea derivative of histidine, inhibits mushroom tyrosinase activity in a dose-dependent manner, with an IC(50) value of 1.025 mg/ml (4.47 mM). By contrast, histidine exhibited no inhibitory effect on mushroom tyrosinase activity. We characterized ergothioneine as a noncompetitive tyrosinase inhibitor using a Lineweaver-Burk plot of experimental kinetic data. The IC(50) value for ergothioneine scavenging of 2,2-diphenyl-1-picrylhydrazyl was 6.110 +/- 0.305 mg/ml, much higher than the IC(50) for inhibition of tyrosinase activity which indicating ergothioneine on tyrosinase shows a weak correlation to its antioxidative activity. The results demonstrated that ergothioneine has a potent inhibition effect on tyrosinase enzyme activity, resulting from the presence of the sulfur substituted imidazole ring in ergothioneine. PMID- 22068691 TI - Chemiluminescent detection of carbohydrates in the tumoral breast diseases. AB - Nowadays, there is an increase of investigations into the fibroadenoma, mainly because some studies have shown that the occurrence of fibroadenoma is linked to an increased risk of developing breast carcinoma. Currently, the chemiluminescence biomarkers are applied for validation methods and screening. Here, a lectin chemiluminescence is proposed as new histochemistry method to identify carbohydrates in mammary tumoral tissues. The lectins concanavalin A (Con A) and peanut agglutinin (PNA) conjugated to acridinium ester were used to characterize the glycocode of breast tissues: normal, fibroadenoma, and invasive duct carcinoma (IDC). The lectin chemiluminescence expressed in relative light units (RLU) was higher in fibroadenoma and IDC than in normal tissue for both lectins tested. The relationship RLU emission versus tissue area described a linear and hyperbolic curve for IDC and fibroadenoma, respectively, using Con A whereas hyperbolic curves for both transformed tissues using PNA. RLU was abolished by inhibiting the interaction between tissues and lectins using their specific carbohydrates: methyl-alpha-D: -mannoside (Con A) and galactose (PNA). The intrinsic fluorescence emission did not change with combination of the lectins (Con A/PNA) to the acridinium ester for hydrophobic residues. These results represent the lectin chemiluminescence as an alternative of histochemistry method for tumoral diagnosis in the breast. PMID- 22068692 TI - Dendrites: there's a NAK to branching out. PMID- 22068693 TI - Synaptic plasticity: tuning electrical synapses. PMID- 22068694 TI - Learning and memory: CA1 triggers the trace. PMID- 22068695 TI - Ovarian antral folliculogenesis during the human menstrual cycle: a review. AB - BACKGROUND Ovarian follicles undergo dynamic morphologic and endocrinologic changes during the human menstrual cycle. The physiologic mechanisms underlying recruitment and selection of antral follicles in women are not fully elucidated. METHODS A comprehensive review of >200 studies was conducted using PubMed. The objective was to compare and contrast different perspectives on human antral folliculogenesis. RESULTS Antral folliculogenesis has been studied using histologic, endocrinologic and/or ultrasonographic techniques. Different theories of antral follicle recruitment include: (i) continuous recruitment throughout the menstrual cycle; (ii) recruitment of a 'cohort' of antral follicles once in the late-luteal phase or early-follicular phase of each cycle and (iii) recruitment of two or three 'cohorts' or 'waves' during each cycle. Generally, a single dominant follicle is selected in the mid-follicular phase of each cycle and this follicle ovulates at mid-cycle. However, a dominant follicle may also be selected during anovulatory waves that precede the ovulatory wave in some women. CONCLUSIONS There is increasing evidence to indicate that multiple waves of antral follicles develop during the human menstrual cycle. Ovarian follicular waves in women are comparable with those documented in several animal species; however, species-specific differences exist. Enhancing our understanding of the endocrine and paracrine mechanisms underlying antral follicular wave dynamics has clinical implications for understanding age-related changes in reproductive function, optimizing hormonal contraceptive and ovarian stimulation regimens and identifying non-invasive markers of the physiologic status of follicles which are predictive of oocyte competence and assisted reproduction outcomes. PMID- 22068696 TI - The effect of rhPTH on the healing of tendon to bone in a rat model. AB - Successful rotator cuff tendon repair depends on secure tendon-to-bone healing. Recombinant human parathyroid hormone (rhPTH) has been shown in multiple studies to accelerate bone healing. Recent studies have also shown that rhPTH is chondrogenic by increasing chondrocyte recruitment and differentiation. We hypothesized that rhPTH would improve tendon-to-bone healing in a rat rotator cuff repair model. One hundred and fourteen Sprague Dawley rats underwent division and repair of the supraspinatus tendon. Fifty seven rats received daily subcutaneous injections of 10 ug/kg of rhPTH. Rats were sacrificed at 3, 7, 14, 28, and 56 days for histologic and immunohistochemical analysis. In addition, rats in each group were sacrificed at 14, 28, and 56 days for biomechanical testing and micro CT analysis. At 2 weeks the controls had a significantly higher load to failure than the rhPTH group. At 28 and 56 days there were no differences in load to failure. rhPTH specimens had significantly higher stiffness at 56 days. MicroCT analysis showed that the rhPTH group had significantly greater total mineral content at all time points, as well as significantly higher bone volume (BV) at 14 and 28 days. Histologically, the rhPTH specimens had more fibrocartilage, osteoblasts, and blood vessels at all timepoints, with significantly better collagen fiber orientation at 28 and 56 days. Although treatment with rhPTH resulted in an increase in bone and mineralized fibrocartilage formation, as well as better collagen fiber organization, this did not translate into improved biomechanical properties. PMID- 22068697 TI - Sesquiterpene synthases: passive catalysts or active players? AB - Sesquiterpene synthases catalyse the metal dependent turnover of farnesyl diphosphate to generate a class of natural products characterised by an enormous diversity in structure, stereochemistry, biological function and application. It has been proposed that these enzymes take a passive role in the reactions they catalyse and that they serve mostly as stereochemical templates, within which the reactions take place. Here, recent research into the structure and function of sesquiterpene synthases and the mechanisms of the reactions that they catalyse will be reviewed to suggest that these fascinating enzymes play multifaceted active roles in what are arguably the most complex biosynthetic reactions. PMID- 22068698 TI - Two-stage posterior-only procedures for correction of severe spinal deformities. AB - PURPOSE: To review the outcomes of surgical treatment for severe spinal deformities via a two-stage posterior-only approach. METHODS: A total of 18 patients with large and rigid spinal deformities were studied based on clinical and radiographic data. All of them received a two-stage posterior-only approach: first on the concave side by internal distraction of pedicle screws and rods through intramuscular tunnels, followed by respiratory function exercise and improving nutritional status during the intervening period, and finally by posterior additional correction, ultimate instrumentation and spinal fusion in the second operation. RESULTS: The mean major coronal curve was corrected by 46% after the first operation and by 60.4% after the second operation. The mean thoracic kyphosis was corrected by 50.9% after the first operation and by 64.8% after the second operation. The loss of correction mean was 3.3 degrees for the major coronal curve and 2.6 degrees for the thoracic kyphosis at a mean of 31.5 months follow-up. The mean operation time for the first and second operation was 186.2 and 300.6 min, and the mean intraoperative blood loss was 211.1 and 1,597.2 mL, respectively. No severe complication was noticed in this series. CONCLUSIONS: The two-stage posterior-only procedures permitting stepwise correction for the treatment of severe spinal deformities provide safe and satisfactory outcomes in this patient population. PMID- 22068699 TI - Staff workload and adverse events during mechanical ventilation in neonatal intensive care units. AB - OBJECTIVE: To investigate a possible association between the intensity of staff workload and intermediate adverse events, such as accidental extubation, obstruction of the endotracheal tube, and accidental disconnection of the ventilator circuit, during neonatal mechanical ventilation in high-risk neonatal units. METHOD: This prospective cohort study analyzed data of 543 newborns from public neonatal intensive care units (NICUs) in the city of Sao Luis, state of Maranhao, Northeastern Brazil, for 6 months, during which 136 newborns were submitted to mechanical ventilation in 1,108 shifts and were observed a total of 4,554 times. RESULTS: Adverse events occurred 117 times during this period. The associations between workload and adverse events were analyzed by means of generalized estimating equations. The adjustment variables were: birth weight, gender, maternity unit, Clinical Risk Index for Babies score, and care demand, the latter measured by the Northern Neonatal Network Scale. The larger the number of newborns classified by care demand (NCCD) per nurse and nursing technician, the more likely the occurrence of intermediate adverse events linked to mechanical ventilation. A number of NCCD > 22 per nurse (relative risk [RR] = 2.86) and > 4.8 per auxiliary nurse (RR = 3.41) was associated with a higher prevalence of intermediate adverse events. CONCLUSIONS: The workload of NICU professionals seems to interfere with the intermediate results of neonatal care and thus should be taken into consideration when evaluating NICU outcomes. PMID- 22068700 TI - Moderate sedation for elective upper endoscopy with balanced propofol versus fentanyl and midazolam alone: a randomized clinical trial. AB - BACKGROUND AND STUDY AIMS: Balanced propofol sedation (BPS) combines propofol with opiates and benzodiazepines and targets at moderate sedation. Data comparing outcomes of BPS and standard sedation with opiates and benzodiazepines during elective esophagogastroduodenoscopy (EGD) are sparse. The primary end point of this study was to compare, in the recovery area, patient satisfaction with EGD following BPS versus standard sedation. PATIENTS AND METHODS: Prospective, single blinded randomized trial in 110 outpatients undergoing elective EGD and randomized 1:1 to BPS or standard sedation. Upon full recovery, the primary outcome of patient satisfaction was assessed using a 100-mm visual analogue scale (VAS) (1 = not at all satisfied, 100 = completely satisfied). Sedation recovery times and recall of pain and gagging (1 = none, 100 = severe) were also evaluated using a VAS. RESULTS: The BPS and standard sedation groups were similar regarding American Society of Anesthesiologists (ASA), Mallampati class, age, sex, and body mass index (BMI). Compared with the standard sedation arm, the BPS group exhibited higher median procedural satisfaction (99 vs. 85, P < 0.001), and lower median scores for recall of pain (P < 0.001) and gagging (P < 0.001). BPS resulted in a shorter median recovery time (min) (11 vs. 23, P < 0.001). On multivariable regression analysis, predictors of patient satisfaction included use of propofol, increased age, and higher fentanyl dosage. CONCLUSIONS: BPS targeted to moderate sedation by adequately trained endoscopists results in superior patient satisfaction and shorter recovery times than standard sedation alone during EGD. PMID- 22068701 TI - Complete Barrett's excision by stepwise endoscopic resection in short-segment disease: long term outcomes and predictors of stricture. AB - BACKGROUND AND STUDY AIMS: Complete Barrett's excision (CBE) of short-segment Barrett's high grade dysplasia (HGD) and early esophageal adenocarcinoma by stepwise endoscopic resection is a precise staging tool, detects covert synchronous disease, and may produce a sustained treatment response. Esophageal stricture is the most commonly reported complication of CBE although risk factors have not yet been clearly defined. PATIENTS AND METHODS: Data were recorded prospectively on patients with limited co-morbidity and age <= 80 years undergoing CBE for histologically proven HGD or esophageal adenocarcinoma within <= C3M5 segments. Endoscopic resection was performed by standardized protocol every 6 - 8 weeks until CBE was achieved. Esophageal dilation was performed when patients reported dysphagia. Dysphagia scores were recorded at scheduled endoscopic surveillance or by telephone interview. RESULTS: By intention-to-treat analysis, complete eradication of neoplasia and intestinal metaplasia was achieved in 95 % and 82 %, respectively, in 77 patients undergoing a median of 2 resection sessions (interquartile range [IQR] 1 - 3). Esophageal dilation was required in 33 % (median 3 dilations, IQR 1 - 3.5) at median follow-up of 20 months (IQR 6 - 40). Independent risk factors for dilation requirement were the number of mucosal resections at the index procedure (odds ratio [OR] 1.3 per resection, 95 % confidence interval [CI] 1.0 - 1.9; P = 0.043) and maximal extent of the Barrett's segment (OR 2.2 per cm, 95 %CI 1.2 - 3.9; P = 0.009). CONCLUSIONS: Although CBE is highly effective in the treatment of Barrett's HGD and esophageal adenocarcinoma, the risk of post-CBE dysphagia increases with the maximal extent of the Barrett's segment and the number of mucosal resections at the index procedure. These data could be used to inform treatment decisions and identify those patients who may benefit from prophylactic therapies such as dilation. PMID- 22068702 TI - Initial evaluation of a novel multibending backward-oblique viewing duodenoscope in endoscopic retrograde cholangiopancreatography. AB - A novel multibending backward-oblique viewing duodenoscope was developed to overcome the difficult technical aspect of deep cannulation into the bile duct during endoscopic retrograde cholangiopancreatography (ERCP). The aim of the present study was to evaluate the initial experience of a novel multibending backward-oblique viewing duodenoscope (M-D scope) for ERCP. This was a retrospective review of 23 patients with native papilla who received biliary ERCP with the M-D scope between April and December 2010. The procedures were performed by two well-experienced endoscopists. In all patients, biliary cannulation and therapeutic procedure were successfully completed. In two patients with Billroth I gastrectomy, ERCP were initially attempted with a conventional single-bending duodenoscope, but biliary cannulations were unsuccessful. However, with the use of the M-D scope, biliary cannulation and therapeutic procedures were successfully completed. A novel multibending backward-oblique viewing duodenoscope is safe and feasible for therapeutic and diagnostic ERCP. PMID- 22068703 TI - Gastrointestinal endoscopy in a low budget context: delegating EGD to non physician clinicians in Malawi can be feasible and safe. AB - Gastrointestinal endoscopy is rarely performed in low-income countries in sub Saharan Africa. One reason is the lack of available medical doctors and specialists in these countries. At Zomba Central Hospital in Malawi, clinical officers (non-physician clinicians with 4 years of formal training) were trained in upper gastrointestinal endoscopy. Prospectively recorded details of 1732 consecutive esophagogastroduodenoscopies (EGDs) performed between September 2001 and August 2010 were analyzed to evaluate whether upper gastrointestinal endoscopy can be performed safely and accurately by clinical officers. A total of 1059 (61.1%) EGDs were performed by clinical officers alone and 673 (38.9%) were carried out with a medical doctor present who performed or assisted in the procedure. Failure and complication rates were similar in both groups (P=0.105). Endoscopic diagnoses for frequent indications were generally evenly distributed across the two groups. The main difference was a higher proportion of normal findings and a lower proportion of esophagitis in the group with a doctor present, although this was significant only in patients who had presented with epigastric/abdominal pain (P<0.001). In conclusion, delegating upper gastrointestinal endoscopy to clinical officers can be feasible and safe in a setting with a shortage of medical doctors when adequate training and supervision are provided. PMID- 22068704 TI - A homogeneous, high-throughput-compatible, fluorescence intensity-based assay for UDP-N-acetylenolpyruvylglucosamine reductase (MurB) with nanomolar product detection. AB - A novel assay for the NADPH-dependent bacterial enzyme UDP-N acetylenolpyruvylglucosamine reductase (MurB) is described that has nanomolar sensitivity for product formation and is suitable for high-throughput applications. MurB catalyzes an essential cytoplasmic step in the synthesis of peptidoglycan for the bacterial cell wall, reduction of UDP-N acetylenolpyruvylglucosamine to UDP-N-acetylmuramic acid (UNAM). Interruption of this biosynthetic pathway leads to cell death, making MurB an attractive target for antibacterial drug discovery. In the new assay, the UNAM product of the MurB reaction is ligated to L-alanine by the next enzyme in the peptidoglycan biosynthesis pathway, MurC, resulting in hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP). The ADP is detected with nanomolar sensitivity by converting it to oligomeric RNA with polynucleotide phosphorylase and detecting the oligomeric RNA with a fluorescent dye. The product sensitivity of the new assay is 1000-fold greater than that of the standard assay that follows the absorbance decrease resulting from the conversion of NADPH to NADP(+). This sensitivity allows inhibitor screening to be performed at the low substrate concentrations needed to make the assay sensitive to competitive inhibition of MurB. PMID- 22068705 TI - Establishment of a stable cell line coexpressing dengue virus-2 and green fluorescent protein for screening of antiviral compounds. AB - This study aimed to generate a stable cell line harboring subgenomic dengue virus replicon and a green fluorescent gene (DENV/GFP) for a cell-based model to screen anti-DENV compounds. The gene-encoding envelope protein of DENV-2 was deleted and then replaced with fragments of the GFP gene and a foot-and-mouth-disease virus 2A-derived cleavage site. The human cytomegalovirus immediate early and antisense hepatitis delta virus ribozyme sequences were added at the 5'- and 3'-ends. An internal ribosome entry site and neomycin resistance genes were placed upstream and next to the NS1 gene. The recombinant plasmids were propagated in a mammalian cell line. A stable cell line with the brightest green fluorescent protein and the highest viral protein and RNA expression was selected from six clones. The clone was then examined for effectiveness in an antiviral drug screening assay with compounds isolated from the local plants using two known antiviral agents as controls. Two novel flavones, PMF and TMF, were discovered having DENV-inhibitory properties. The data were validated by a conventional plaque titration assay. The results indicate that this newly developed cell line is efficient for use as a cell-based model for primary screening of anti-DENV compounds. PMID- 22068706 TI - Biosensor-based approach to the identification of protein kinase ligands with dual-site modes of action. AB - The authors have used a surface plasmon resonance (SPR)-based biosensor approach to identify and characterize compounds with a unique binding mode to protein kinases. Biacore was used to characterize hits from an enzymatic high-throughput screen of the Tec family tyrosine kinase, IL2-inducible T cell kinase (ITK). Complex binding kinetics was observed for some compounds, which led to identification of compounds that bound simultaneously at both the adenosine triphosphate (ATP) binding site and a second, allosteric site on ITK. The presence of the second binding site was confirmed by X-ray crystallography. The second site is located in the N-terminal lobe of the protein kinase catalytic domain, adjacent to but distinct from the ATP site. To enable rapid optimization of binding properties, a competition-based Biacore assay has been developed to successfully identify second site noncompetitive binders that have been confirmed by X-ray crystallographic studies. The authors have found that SPR technology is a key method for rapid identification of compounds with dual-site modes of action. PMID- 22068707 TI - A homogeneous fluorescent assay for cAMP-phosphodiesterase enzyme activity. AB - Cyclic adenosine monophosphate-phosphodiesterases (cAMP-PDEs) regulate the cellular level of cAMP by selectively catalyzing the hydrolysis of the phosphodiester bond in the cAMP molecule. They play important roles in modulating cellular and physiological functions. There is a growing interest in the study of cAMP-PDEs as therapeutic targets. We describe a novel method for measuring the enzyme activity of cAMP-PDEs that is based on a homogeneous fluorescence assay employing a cAMP-dependent DNA-binding protein (CAP). We demonstrate that the assay is quick and robust compared to traditional methods and is expected to be cost-effective for high-throughput screening of cAMP-PDE inhibitors. The usefulness of the assay is demonstrated by measuring IC(50) values of three nonselective PDE inhibitors and by kinetic measurements of cAMP-PDEs from various rat tissues. PMID- 22068708 TI - Layer-by-layer evolution and a hysteretic single-crystal to single-crystal transformation cycle of a flexible pillared-layer open framework. AB - Two hypothetical crystal-growth intermediates of a new pillared-layer framework have been isolated. The seemingly rigid pillared-layer framework also undergoes temperature-induced, time-dependent, hysteretic framework distortion. PMID- 22068709 TI - Community sodium reduction: is it worth the effort? PMID- 22068710 TI - Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review). AB - BACKGROUND: The question of whether reduced sodium intake is effective as a health prophylaxis initiative is unsolved. The purpose was to estimate the effects of low-sodium vs. high-sodium intake on blood pressure (BP), renin, aldosterone, catecholamines, and lipids. METHODS: Studies randomizing persons to low-sodium and high-sodium diets evaluating at least one of the above outcome parameters were included. Data were analyzed with Review Manager 5.1. RESULTS: A total of 167 studies were included. The effect of sodium reduction in: (i) Normotensives: Caucasians: systolic BP (SBP) -1.27 mm Hg (95% confidence interval (CI): -1.88, -0.66; P = 0.0001), diastolic BP (DBP) -0.05 mm Hg (95% CI: -0.51, 0.42; P = 0.85). Blacks: SBP -4.02 mm Hg (95% CI: -7.37, -0.68; P = 0.002), DBP 2.01 mm Hg (95% CI: -4.37, 0.35; P = 0.09). Asians: SBP -1.27 mm Hg (95% CI: 3.07, 0.54; P = 0.17), DBP -1.68 mm Hg (95% CI: -3.29, -0.06; P = 0.04). (ii) Hypertensives: Caucasians: SBP -5.48 mm Hg (95% CI: -6.53, -4.43; P < 0.00001), DBP -2.75 mm Hg (95% CI: -3.34, -2.17; P < 0.00001). Blacks: SBP -6.44 mm Hg (95% CI: -8.85, -4.03; P = 0.00001), DBP -2.40 mm Hg (95% CI: -4.68, -0.12; P = 0.04). Asians: SBP -10.21 mm Hg (95% CI: -16.98, -3.44; P = 0.003), DBP -2.60 mm Hg (95% CI: -4.03, -1.16; P = 0.0004). Sodium reduction resulted in significant increases in renin (P < 0.00001), aldosterone (P < 0.00001), noradrenaline (P < 0.00001), adrenaline (P < 0.0002), cholesterol (P < 0.001), and triglyceride (P < 0.0008). CONCLUSIONS: Sodium reduction resulted in a significant decrease in BP of 1% (normotensives), 3.5% (hypertensives), and a significant increase in plasma renin, plasma aldosterone, plasma adrenaline, and plasma noradrenaline, a 2.5% increase in cholesterol, and a 7% increase in triglyceride. PMID- 22068711 TI - Public health policies: no place for surrogates. PMID- 22068712 TI - Face emotion processing in depressed children and adolescents with and without comorbid conduct disorder. AB - Studies of adults with depression point to characteristic neurocognitive deficits, including differences in processing facial expressions. Few studies have examined face processing in juvenile depression, or taken account of other comorbid disorders. Three groups were compared: depressed children and adolescents with conduct disorder (n = 23), depressed children and adolescents without conduct disorder (n = 29) and children and adolescents without disorder (n = 37). A novel face emotion processing experiment presented faces with 'happy', 'sad', 'angry', or 'fearful' expressions of varying emotional intensity using morphed stimuli. Those with depression showed no overall or specific deficits in facial expression recognition accuracy. Instead, they showed biases affecting processing of low-intensity expressions, more often perceiving these as sad. In contrast, non-depressed controls more often misperceived low intensity negative emotions as happy. There were no differences between depressed children and adolescents with and without conduct disorder, or between children with comorbid depression/conduct disorder and controls. Face emotion processing biases rather than deficits appear to distinguish depressed from non-depressed children and adolescents. PMID- 22068713 TI - Gender differences in psychopathic traits, types, and correlates of aggression among adjudicated youth. AB - The current study investigated gender differences in types and correlates of aggression among 150 adjudicated youth (M age = 15.2, SD = 1.4). In cluster analysis, consistent with past studies, one aggressive group characterized by moderate levels of reactive aggression and one characterized by high levels of proactive and reactive aggression emerged and these patterns were consistent across gender. For both boys and girls, the combined proactive/reactive aggression cluster showed the greatest levels of aggression, impulsivity, and callous-unemotional traits, supporting a severity over a typology model of proactive and reactive aggression. Girls displayed significantly higher rates of physical and relational aggression than boys. Girls were highly aggressive toward both girls and boys, whereas boys were highly aggressive only toward other boys. Girls also showed multiple indications of severity and emotionality, indexed by higher rates of negative affect, anxiety, distress about social provocations, and empathy. PMID- 22068715 TI - Distal anterior choroidal artery aneurysm following iatrogenic posterior cerebral artery occlusion : a case report and review of literature. AB - Aneurysms of the anterior choroidal artery are uncommon and account for only 2-5% of all intracranial aneurysms. Distal anterior choroidal artery aneurysms are rare and the pathogenesis of this aneurysm may be different from typical proximal ones. We describe an unusual case of ruptured de novo distal anterior choroidal artery aneurysm in a 55 year-old man who had previously undergone endovascular proximal occlusion for a fusiform aneurysm of the ipsilateral posterior cerebral artery (PCA). A comprehensive review of literature using Medline, PubMed and all related journals was also performed. Only 34 reported distal AchoA aneurysms were found: 16 associated with moyamoya disease, 10 idiopathic, two with atherosclerosis, two with arteriovenous malformation, two dissecting, one infectious and one due to trauma. It is probable that the increased hemodynamic stress within the AchoA contributed to the formation and rupture of the reported aneurysm. This late complication needs to be considered when large intracranial vessels are iatrogenically occluded in the management of complex intracranial aneurysms. PMID- 22068716 TI - An innovative method for detecting surgical errors using indocyanine green angiography during carotid endarterectomy: a preliminary investigation. AB - BACKGROUND: Carotid endarterectomy (CEA) is the most effective treatment method of carotid stenosis or occlusion. Surgeons typically check the blood flow in each vessel using Duplex Doppler ultrasonography or radiocontrast angiography in order to prevent postoperative complications. Embolic cerebral infarction on the ipsilateral side has been reported in 4-7% of patients undergoing CEA despite a tolerable blood flow reported by Duplex ultrasonography. This study was designed to evaluate a new intraoperative method for detecting technical errors during CEA using indocyanine green (ICG) angiography. METHODS: Six consecutive patients with severe carotid stenosis or occlusion underwent CEA. Both ICG angiography and Doppler ultrasonography were performed before the carotid arterial incision and after the carotid arterial suture. After injecting ICG dye via an intravenous route, the internal surface, atheroma, and flow defect were visualized with a microscope. RESULTS: In ICG angiography, stenotic lesions could be identified as regions of relatively dark signal intensity. Magnified real-time images could be created using a microscope with an infrared filter, including three-dimensional images and detailed images of the inner lumen. These images could then be compared with the results of Doppler ultrasonography. In the six cases assessed by both ICG angiography and Doppler ultrasonography, all Doppler results were acceptable. However, one patient underwent revision surgery because a fluttering atheroma was detected by ICG angiography. ICG angiography could assume the extent of severe stenotic area. ICG angiography could also detect mobile lesions such as a fluttering atheroma. CONCLUSIONS: Intraoperative ICG angiography before arteriotomy is useful to determine the precise stenotic area and the shape of the associated plaque. ICG angiography after an arteriotomy site is sutured is also useful for detecting residual stenosis or fluttering atheroma. ICG angiography could be an alternative method to Doppler ultrasonography for ensuring a complete and successful operation and preventing complications. PMID- 22068717 TI - Intentional partial coiling dome protection of complex ruptured cerebral aneurysms prevents acute rebleeding and produces favorable clinical outcomes. AB - BACKGROUND: The coiling of ruptured cerebral aneurysms protects against acute rebleeding; however, whether partially coiling a ruptured cerebral aneurysm protects against acute rebleeding has never been demonstrated. OBJECTIVE: This study was performed to test our hypothesis that intentional partial coiling of complex ruptured cerebral aneurysms, which are unfavorable for clipping and cannot be completely coiled primarily, prevents acute rebleeding to allow for clinical and neurological recovery until definitive treatment and produces favorable clinical outcomes. METHODS: Data were collected from the prospective databases of three centers. Only subarachnoid hemorrhage patients that were treated with a strategy of intentional partial coiling for dome protection were included. This did not include patients in whom the goal was complete coiling but only subtotal coil occlusion was achieved. RESULTS: Fifteen patients [aged 51 +/- 13 years; HH 3-5 (n = 7); Fisher 3-4 (n = 9)] were treated with intentional partial dome protection. Aneurysm size was 12.8 +/- 5.4 mm; neck size 4.9 +/- 3 mm; 12 anterior circulation. Four intentional partial coilings were performed with balloon assistance. Definitive treatment was performed 92 +/- 90 days later, with no case of rebleeding. Definitive treatment was clipping (n = 8), stent coiling (n = 5), Onyx (n = 1), further coiling (n = 1). Clinical outcome was favorable in 13 cases (GOS 4-5), fair in one (GOS 3), and death in one (GOS 1). CONCLUSIONS: Judicious use of a treatment strategy of intentional partial dome protection for complex aneurysms that are not favorable for clipping and in which complete coiling primarily is not possible may prevent acute rebleeding and produce favorable clinical outcomes. PMID- 22068718 TI - Magnetization, Mossbauer and isothermal dilatometric behavior of oxidized YBa(Co,Fe)4O(7+delta). AB - Mossbauer spectroscopy and magnetization studies of YBaCo(4-x)Fe(x)O(7+delta) (x = 0-0.8) oxidized at 0.21 and 100 atm O(2), indicate an increasing role of penta coordinated Co(3+) states when the oxygen content approaches 8-8.5 atoms per formula unit. Strong magnetic correlations are observed in YBaCo(4-x)Fe(x)O(8.5) from 2 K up to 55-70 K, whilst the average magnetic moment of Co(3+) is lower than that for delta <= 0.2, in correlation with the lower (57)Fe(3+) isomer shifts determined from Mossbauer spectra. The hypothesis on dominant five-fold coordination of cobalt cations was validated by molecular dynamics modeling of YBaCo(4)O(8.5). The iron solubility limit in YBaCo(4-x)Fe(x)O(7+delta) corresponds to approximately x ~ 0.7. The oxygen intercalation processes in YBaCo(4)O(7+delta) at 470-700 K, analyzed by X-ray diffraction, thermogravimetry and controlled-atmosphere dilatometry, lead to unusual volume expansion opposing to the cobalt cation radius variations. This behavior is associated with increasing cobalt coordination numbers and with rising local distortions and disorder in the crystal lattice on oxidation, predicted by the computer simulations. When the oxygen partial pressure increases from 4 * 10(-5) to 1 atm, the linear strain in YBaCo(4)O(7+delta) ceramics at 598 K is as high as 0.33%. PMID- 22068719 TI - Analysis of T-wave Amplitude Adaptation to Heart Rate Using RR-binning of Long Term ECG Recordings. AB - The prognosis of patients with coronary artery disease at the early stage of the disease is a challenge of modern cardiology. There is an urgent need to risk stratify these patients. Holter technology is a cheap and cost effective tool to evaluate electrical abnormalities in the heart. We propose to investigate T amplitude adaptation to heart rate (HR) using RR-binning. We used daytime recordings from healthy subjects and subjects with acute myocardial infarction (AMI) from the Telemetric and Holter ECG Warehouse. The AMI subjects were divided into two groups based on location of their infarction (group A: anterior or anterior lateral, group B: inferior or inferior lateral). Both AMI groups had acute and stable phase recordings. Population-based T-adaptation to HR was observed for healthy subjects (R2 = 0.92) but was less pronounced for AMI subjects: [Formula: see text]. PMID- 22068720 TI - Modeling and design of optimal flow perfusion bioreactors for tissue engineering applications. AB - Perfusion bioreactors have been used in different tissue engineering applications because of their consistent distribution of nutrients and flow-induced shear stress within the tissue-engineering scaffold. A widely used configuration uses a scaffold with a circular cross-section enclosed within a cylindrical chamber and inlet and outlet pipes which are connected to the chamber on either side through which media is continuously circulated. However, fluid-flow experiments and simulations have shown that the majority of the flow perfuses through the center. This pattern creates stagnant zones in the peripheral regions as well as in those of high flow rate near the inlet and outlet. This non-uniformity of flow and shear stress, owing to a circular design, results in limited cell proliferation and differentiation in these areas. The focus of this communication is to design an optimized perfusion system using computational fluid dynamics as a mathematical tool to overcome the time-consuming trial and error experimental method. We compared the flow within a circular and a rectangular bioreactor system. Flow simulations within the rectangular bioreactor are shown to overcome the limitations in the circular design. This communication challenges the circular cross-section bioreactor configuration paradigm and provides proof of the advantages of the new design over the existing one. PMID- 22068721 TI - Children's exposure to metals: a community-initiated study. AB - In 2007, it was shown that the shipping of lead (Pb) through Esperance Port in Western Australia resulted in contamination and increased Pb concentrations in children. A clean-up strategy was implemented; however, little attention was given to other metals. In consultation with the community, a cross-sectional exposure study was designed. Thirty-nine children aged 1 to 12 years provided samples of hair, urine, drinking water, residential soil and dust. Concentrations of nickel (Ni) and Pb were low in biological and environmental samples. Hair aluminium (Al) (lower than the detection limit [DL] to 251 MUg/g) and copper (Cu) (7 to 415 MUg/g), as well as urinary Al (
Pt2 > Pt3. PMID- 22068825 TI - A method for analysis of lipid vesicle domain structure from confocal image data. AB - Quantitative characterization of the lateral structure of curved membranes based on fluorescence microscopy requires knowledge of the fluorophore distribution on the surface. We present an image analysis approach for extraction of the fluorophore distribution on a spherical lipid vesicle from confocal imaging stacks. The technique involves projection of volumetric image data onto a triangulated surface mesh representation of the membrane, correction of photoselection effects and global motion of the vesicle during image acquisition and segmentation of the surface into domains using histograms. The analysis allows for investigation of the morphology and size distribution of domains on the surface. PMID- 22068826 TI - Observation of protein folding/unfolding dynamics of ubiquitin trapped in agarose gel by single-molecule FRET. AB - A ubiquitin mutant with two Cys mutations, m[C]q/S65C, was site-specifically labeled with two dye molecules, Alexa Fluor 488 (donor) and Alexa Fluor 594 (acceptor), due to the different reactivity of these two Cys residues. This doubly dye-labeled ubiquitin has lower structural stability than wild-type ubiquitin. Taking advantage of this decreased stability, conformational heterogeneity of this protein under nondenaturing condition was observed at the single-molecule level using single-paired Forster resonance energy transfer (FRET) by trapping the protein in agarose gel. Three conformational populations corresponding to folded (E (ET) ~ 0.95), loosely packed (E (ET) ~ 0.72), and unfolded (E (ET) ~ 0.22) structures, and the structural transitions between them were observed. Our results suggest that agarose immobilization is good for observing structural dynamics of proteins under native condition. PMID- 22068827 TI - Guanine triphosphate-cyclohydrolase 1-deficient dopa-responsive dystonia presenting as frequent falling in 2 children. AB - Guanine triphosphate (GTP)-cyclohydrolase 1 (GCH1)-deficient dopa-responsive dystonia is caused by GCH1 gene mutation. Two children presenting with frequent daily falling are reported with GCH1 gene mutations with persistent response to low-dose levodopa/carbidopa. Typical and atypical clinical features associated with GCH1 mutations are also reviewed. PMID- 22068828 TI - Evaluation of intraventricular hemorrhage in pediatric intracerebral hemorrhage. AB - Previous studies of pediatric intracerebral hemorrhage have investigated isolated intraparenchymal hemorrhage. The authors investigated whether detailed assessment of intraventricular hemorrhage enhanced outcome prediction after intracerebral hemorrhage. They prospectively enrolled 46 children, full-term to 17 years, median age 2.7 years, with spontaneous intraparenchymal hemorrhage and/or intraventricular hemorrhage. Outcome was assessed with the King's Outcome Scale for Childhood Head Injury. Twenty-six (57%) had intraparenchymal hemorrhage, 10 (22%) had pure intraventricular hemorrhage, and 10 (22%) had both. There were 2 deaths, both with intraparenchymal hemorrhage and intraventricular hemorrhage volume >=4% of total brain volume. Presence of intraventricular hemorrhage was not associated with poor outcome, but hydrocephalus showed a trend (P = .09) toward poor outcome. In receiver operating characteristic curve analysis, combined intraparenchymal hemorrhage and intraventricular hemorrhage volume also showed a trend toward better outcome prediction than intraparenchymal hemorrhage volume alone. Although not an independent outcome predictor, future studies should assess intraventricular hemorrhage qualitatively and quantitatively. PMID- 22068829 TI - Skewed allele-specific expression of the NF1 gene in normal subjects: a possible mechanism for phenotypic variability in neurofibromatosis type 1. AB - Neurofibromatosis type 1 is an autosomal dominant disorder characterized by neurocutaneous abnormalities, learning disabilities, and attention-deficit disorder. Neurofibromatosis type 1 symptom severity can be highly variable even within families where all affected members carry the same mutation. We hypothesized that variation in the expression of the normal NF1 allele may be a mechanism that participates in producing variable phenotypes. We performed allelic expression imbalance assays on healthy control individuals to estimate the prevalence of skewed allelic expression of the NF1 gene. Approximately 30% of individuals in our sample population showed significant skewing of allelic expression away from the expected 50:50 ratio, indicating that differential regulation of the NF1 alleles occurs in a high proportion of individuals. Differences of up to 25% in allele-specific expression of the NF1 alleles were identified. In individuals with Neurofibromatosis type 1, who carry a mutant allele (haploinsufficient), this degree of expression skewing may be sufficient to modulate the phenotype. PMID- 22068830 TI - Opioid use and dosing in the workers' compensation setting. A comparative review and new data from Ohio. AB - BACKGROUND: Many authorities are concerned about the rising use and the potential overuse of opioid pain medications. A study of opioid prevalence and dosage in Ohio's workers' compensation (WC) system was conducted, with comparisons made to opioid use in other WC and non-WC settings. METHODS: Systematic literature reviews of WC and non-WC opioid use and dosage nationally were conducted. Two years of Ohio WC data (2008-2009) were analyzed to determine average daily morphine equivalent dose (MED), opioid costs, pharmacies used per claimant, and extent of long-duration cases. RESULTS: Nearly one-fifth (19.2%) of Ohio WC claims involved opioid use, compared to 31.8% in other WC systems and 17.9% in non-WC settings. Mean MED was 57.5 mg, compared to 47.8 mg in other WC systems, and 41.8 mg among non-WC populations. Nearly 10% of WC claims involved relatively high MED exceeding 120 mg/day. CONCLUSION: Policy makers need to develop strategies for addressing high opioid use in WC systems. PMID- 22068831 TI - A Comparison of IIR and Wavelet Filtering for Noise Reduction of the ECG. AB - This study compares the ability to preserve information and reduce noise contaminants on the ECG for five wavelet filters and three IIR filters. Two 3 lead Holter ECGs were used. White Gaussian Noise was added to the first ECG in increments of 10% coverage. The second ECG contained alternating muscle transients and noise-free segments. Computation times and SNR improvements for different noise coverages were calculated and compared. RMS errors were calculated from noise-free segments on the ECG with transient muscle noise. Wavelet filters improved SNR more than IIR filters when the signal coverage was more than 50% noise. In contrast, the computation times were shorter for IIR filters (6 s) than for wavelet filters (88 s). On the ECG with transient muscle noise there was a trade-off in performance between wavelet and IIR filtering. In a clinical setting where the amount of noise is unknown, using IIR filters appears to be preferred for consistent performance. PMID- 22068832 TI - Effect of different intensity pulsed ultrasound on the restoration of rat skeletal muscle contusion. AB - Muscle damage is a common form of injury. The incidence of muscle damage accounts for up to half of the sports injuries. The aim of this study was to investigate the effect of pulsed ultrasound on the healing process in an animal contusion injury model. SD rats (62) were randomly divided into control group (CG, 14 rats) and treatment group (48). According to the intensities of Ultrasound therapy, the treatment group was divided into 4 subgroups of 12 rats, each: A (0.25 W/cm(2), US(1)), B (0.5 W/cm(2), US(2)), C (0.75 W/cm(2), US(3)) and D (0.25 W/cm(2)). The effectiveness of ultrasound treatment on muscle injuries was evaluated, and the optimal intensity of ultrasound in treating muscle injuries was explored. The results obtained provide experimental and theoretical evidence for the clinical effectiveness of Ultrasound therapy in treating muscle injuries. PMID- 22068833 TI - A case study of a high-status human skeleton from Pacopampa in Formative Period Peru. AB - The Pacopampa site is located in the northern highlands of Peru and is an archaeological site belonging to the Formative Period (2500-1 BC). The excavation of the Pacopampa site yielded unusual human skeletons from the main platform of a ceremonial center of the site during the 2009 field season. The skeletal remains were associated with a pair of gold earplugs, a pair of gold earrings, and shell objects. This specimen is possibly a female aged 20-39 years. Detailed examination of the neurocranium revealed the presence of artificial cranial deformation with decreased cranial length, increased cranial breadth, and lateral bulging of the parietal bones. The estimated stature of this individual was 162 cm, which is about 15 cm higher than that of contemporary females of Pacopampa and about 20-25 cm higher than that of other Formative Period sites in northern Peru. The peculiarity of this individual, detected not only in the cultural artifacts but also in the physical features, is possible evidence for social stratification in the Formative Period. PMID- 22068834 TI - Isolation of prostate tumor initiating cells (TICs) through their dielectrophoretic signature. AB - In this study, the dielectrophoretic response of prostate tumor initiating cells (TICs) was investigated in a microfluidic system utilizing contactless dielectrophoresis (cDEP). The dielectrophoretic response of prostate TICs was observed to be distinctively different than that for non-TICs, enabling them to be sorted using cDEP. Culturing the sorted TICs generated spheroids, indicating that they were indeed initiating cells. This study presents the first marker-free TIC separation from non-TICs utilizing their electrical fingerprints through dielectrophoresis. PMID- 22068835 TI - Transportation Difficulty of Black and White Rural Older Adults. AB - The purpose of this study was to understand self-reported transportation difficulty among rural older adults. We used data from the UAB Study of Aging (255 Black and 259 White), community-dwelling participants residing in rural areas. We examined the relationship of predisposing characteristics, enabling resources, and measures of need for care with self-reports of transportation difficulty. Blacks reported having more transportation difficulty than Whites (24.7% vs. 11.6%; p <= .05). When we introduced other variables, race differences disappeared, but there was a race by income interaction with transportation difficulty. Whites with lower incomes were more likely to have transportation difficulty than Whites with higher incomes. When data from Blacks and Whites were analyzed separately, income was the only variable associated with transportation difficulty among Whites. Among Blacks, income was not related to transportation difficulty but several variables other than income (age, gender, marital status, MMSE scores and depression) were. PMID- 22068838 TI - Nanoparticle induced piezoelectric, super toughened, radiation resistant, multi functional nanohybrids. AB - We have developed multifunctional nanohybrids of poly(vinylidene fluoride-co chlorotrifluoroethylene) (CTFE) with a small percentage of surface modified inorganic layered silicate showing dramatic improvement in toughness, radiation resistant and piezoelectric properties vis-a-vis pristine polymer. Massive intercalation (d(001) 1.8 -> 3.9 nm) of polymer inside the nanoclay galleries and unique crystallization behavior of the fluoropolymer on the surface of individual silicate layer has been reported. Toughness in the nanohybrid increases more than three orders of magnitude as compared to pure CTFE. High energy radiation (80 MeV Si(+7)) causes chain session, amorphization and creates olefinic bonds in the pure polymer while the nanohybrids are radiation resistant at a similar dose. Nanoclay induces the metastable piezoelectric beta-phase in CTFE, suitable for sensor and actuator application. Molecular level changes after irradiation and controlled morphology for smart membrane have been confirmed by using spectroscopy, sol-gel technique, surface morphology studies and in situ residual gas analysis. PMID- 22068837 TI - Yeast RNA viruses as indicators of exosome activity: human exosome hCsl4p participates in RNA degradation in Saccharomyces cerevisiae'. AB - The exosome is an evolutionarily conserved 10-mer complex involved in RNA metabolism, located in both the nucleus and the cytoplasm. The cytoplasmic exosome plays an important role in mRNA turnover through its 3'->5' exonucleolytic activity. The superkiller (SKI) phenotype of yeast was originally identified as an increase of killer toxin production due to elevated levels of the L-A double-stranded RNA (dsRNA) Totivirus and its satellite toxin-encoding M dsRNA. Most SKI genes were later shown to be either components of the exosome or modulators of its activity. Variations in the amount of Totivirus are, thus, good indicators of yeast exosome activity, and can be used to analyse its components. Furthermore, if exosome proteins of higher eukaryotes were functional in S. cerevisiae, these viruses would provide a simple tool to analyse their function. In this work, we have found that hCSL4, the human orthologue of SKI4 in the yeast exosome, rescues the null phenotype of the deletion mutant. hCsl4p shares with Ski4p conserved S1 RNA-binding domains, but lacks the N-terminal third of Ski4p. Nevertheless, it interacts with the Dis3p exonuclease of yeast exosome, and partially complements the superkiller phenotype of ski4-1 mutation. The elimination of the N-terminal third of Ski4p does not affect its activity, indicating that it is dispensable for RNA degradation. We have also identified the point mutation G152E in hCSL4, equivalent to the ski4-1 mutation G253E, which impairs the activity of the protein, thus validating our approach of using yeast RNA virus to analyse the exosome of higher eukaryotes. PMID- 22068839 TI - Encapsulated oligothiophenes having electron-affinity characteristics. AB - Oligothiophenes composed of dioxocyclopenta[c]thiophene bearing bulky bis(di-t butylphenyl) groups were designed and synthesized to develop molecular wires having electron-transporting characteristics. Their effective conjugation, electron affinity, and encapsulation effects were investigated by photophysical and electrochemical measurements. PMID- 22068836 TI - MicroRNAs in opioid pharmacology. AB - MicroRNAs (miRNA), a class of ~22-nucleotide RNA molecules, are important gene regulators that bind to the target sites of mRNAs to inhibit the gene expressions either through translational inhibition or mRNA destabilization. There are growing evidences that miRNAs have played several regulatory roles in opioid pharmacology. Like other research fields such as cancer biology, the area where numerous miRNAs are found to be involved in gene regulation, we assume that in opioid studies including research fields of drug additions and opioid receptor regulation, there may be more miRNAs waiting to be discovered. This review will summarize our current knowledge of miRNA functions on opioids biology and briefly describe future research directions of miRNAs related to opioids. PMID- 22068841 TI - Stem cell differentiation depending on different surfaces. AB - Mesenchymal stem cells and 3D biomaterials are a potent assembly in tissue engineering. Today, a sizable number of biomaterials has been characterized for special tissue engineering applications. However, diverse material properties, such as soft or hard biomaterials, have a specific influence on cell behavior. Not only the cell attachment and proliferation, but also differentiation is controlled by the microenvironment. Material characteristics such as pore size, stiffness, roughness, and geometry affect not only the cell attachment and proliferation, but also the differentiation behavior of mesenchymal stem cells. Optimization of these features might enable direct differentiation without adjustment of the culture medium by applying expensive growth or differentiation factors. Future aspects include the design of multilayered biomaterials, where each zone fulfills a distinct function. Moreover, the embedding of growth and differentiation factors into the matrix with a controlled release rate might be advantageous to direct differentiation. PMID- 22068840 TI - Characteristics and management of intractable neck involvement in tularemia: report of 19 patients. AB - The objective of this study is to determine the clinical characteristics and to evaluate the treatment options of intractable neck involvement in tularemia. The medical records of 19 tularemia patients with neck involvement were reviewed retrospectively. On physical examination, fluctuation indicating an abscess formation was detected in 78.9% of the patients. Bilateral involvement was seen in 15.8% of the patients. The most common clinical form was glandular form (63.1%). The most commonly involved lymph node group was upper jugular nodes (78.6%). Six patients underwent incision and drainage procedure, five patients underwent superselective neck dissection and eight patients had only medical treatment. Complete and immediate cure, and better tissue healing with less scarring could be achieved in all patients who underwent superselective neck dissections. In conclusion, intractable neck masses and an abscess can be the initial finding in tularemia, and a high index of suspicion is needed in the differential diagnosis. Superselective neck dissection is a safe and effective option in the treatment of long lasting cervical tularemia unless it responds to medical treatment. PMID- 22068842 TI - Genetic aspects of cell line development from a synthetic biology perspective. AB - Animal cells can be regarded as factories for the production of relevant proteins. The advances described in this chapter towards the development of cell lines with higher productivity capacities, certain metabolic and proliferation properties, reduced apoptosis and other features must be regarded in an integrative perspective. The systematic application of systems biology approaches in combination with a synthetic arsenal for targeted modification of endogenous networks are proposed to lead towards the achievement of a predictable and technologically advanced cell system with high biotechnological impact. PMID- 22068843 TI - First-principles study of electronic and magnetic properties of transition metal adsorbed h-BNC2 sheets. AB - Adsorption of Fe, Co and Ni atoms on a hybrid hexagonal sheet of graphene and boron nitride is studied using density functional methods. Most favorable adsorption sites for these adatoms are identified for different widths of the graphene and boron nitride regions. Electronic structure and magnetic properties of the TM-adsorbed sheets are then studied in detail. The TM atoms change the electronic structure of the sheet significantly, and the resulting system can be a magnetic semiconductor, semi-metal, or a non-magnetic semiconductor depending on the TM chosen. This gives tunability of properties which can be useful in novel electronics applications. Finally, barriers for diffusion of the adatoms on the sheet are calculated, and their tendency to agglomerate on the sheet is estimated. PMID- 22068844 TI - [Whole-body MRI in preoperative diagnostics of breast cancer--a comparison with [corrected] staging methods according to the S 3 guidelines]. AB - PURPOSE: The German Society of Senology (step-3 guidelines for the early recognition of breast cancer in Germany) recommends whole-body staging including chest X-ray, ultrasound of the liver and bone scintigraphy before systemic therapy in patients with breast cancer. The performance of these three examinations is time-consuming and involves radiation exposure. Whole-body MR imaging (WB-MRI) allows staging in a single examination without radiation exposure. The purpose of this study was to compare the diagnostic accuracy of WB MRI with staging according to the guidelines. MATERIALS AND METHODS: During 04/07 and 06/09, the initial staging in 51 patients (56 +/- 12 yrs) with breast cancer (24 patients with lymph node metastases) was performed according to the S 3 guidelines. Additionally, all patients underwent contrast-enhanced WB-MRI (1.5 Tesla-Magnetom Avanto, Siemens, Erlangen). The findings of the different modalities were compared after correlation of the lesions by follow-up. The detection of suspicious findings and the accuracy of prediction of malignancy of the detected lesions were evaluated. RESULTS: Overall, 14 metastases were detected in 4 of 51 patients after completion of the follow-up. By means of WB MRI, all 14 metastases could be detected, while just 4 of these metastases were identified by the conventional methods. CONCLUSION: The detection of distant metastases has an important impact on patient management. In this study WB-MRI in breast cancer staging has shown promising results in regard to possible clinical implementation as a matter of routine staging. PMID- 22068845 TI - [An unusual combination of fibromuscular dysplasia sites]. PMID- 22068846 TI - [Clinical application of flat-panel CT in the angio suite]. AB - The introduction of flat-panel detectors in modern angiographic C-arm systems makes it possible to acquire CT-like images in the angiographic suite (flat-panel CT; FD-CT). In this review, after a short technical introduction of FD-CT including the discussion of the advantages and disadvantages of this new imaging modality, the most commonly and best evaluated indications for FD-CT will be described. FD-CT has become an important adjunctive imaging modality in neurointerventional procedures and embolizations, especially during liver embolization. Another attractive indication for FD-CT is musculoskeletal interventions. FD-CT may provide important additional information in complicated peripheral vascular interventions and stent-graft procedures. FD-CT has a broad spectrum of possible applications, which finally depends on the experience and innovative thinking of the operator. However, it has to be kept in mind that FD CT causes additional radiation exposure. Roughly, it can be assumed that currently one FD-CT sequence causes at least the same radiation exposure as one spiral CT sequence of the corresponding body region. PMID- 22068847 TI - Impact factor and insertion of the ABO in the world scientific literature. PMID- 22068848 TI - [Frequency of occurrence of eyelid basal cell carcinoma in the centralwest region of Sao Paulo State and carriers characteristics]. AB - PURPOSE: To observe the frequency of occurrence of eyelid basal cell carcinoma in the centralwest region of Sao Paulo State and to describe the demographic profile of the basal cell carcinoma carriers. METHODS: Transversal study, using a random sampling, carried out in 12 cities in the centralwest region of Sao Paulo State evolving 11,167 individuals. Patients were evaluated in a Mobile Unit, with complete ophthalmologic evaluation. The diagnosis of eyelid basal cell carcinoma was done through clinical examination and biomicroscopy of the lesion if desirable. The basal cell carcinoma carriers diagnosed were referred to Oculoplastic Clinic of Faculdade de Medicina de Botucatu for treatment. Data were submitted to analysis of frequency of occurrence. RESULTS: Five cases of eyelid basal cell carcinoma were identified in the sample, corresponding to a frequency of occurrence of 0.045%. Four patients were female, most with age equal or greater than 70 year-old and all the cases had white skin color. Only three individuals conveyed attended the service for excision of the lesion and diagnostic confirmation. CONCLUSION: The eyelid basal cell carcinoma affects 0.045% of the inhabitants of the centralwest region of Sao Paulo State, affecting mainly the 70 year-old female range. PMID- 22068849 TI - Cytological features of live limbal tissue donor eyes for autograft or allograft limbal stem cell transplantation. AB - PURPOSE: To evaluate by impression cytology (IC) the corneal surface of live limbal tissue donor eyes for autograft or allograft limbal stem cell transplantation (LSCT). METHODS: Twenty limbal donors were enrolled (17 for autograft LSCT and 3 for allograft). Impression cytology was performed before transplantation of superior and inferior limbal grafts and after the third postoperative month. RESULTS: Impression cytology analysis showed sheets of corneal epithelial cells and goblet cell absence beyond the edge of the keratectomy sites in all patients, suggesting that conjunctival invasion towards the center did not occur in any eye. Partial conjunctivalization within 2 to 3 clock hours, confirmed by the presence of goblet cells, was limited to the keratectomy site in 10% of the cases. CONCLUSION: A clear central corneal surface was demonstrated in all eyes following surgery leading to the conclusion that limbal donation was a safe procedure in this group of patients. A small percentage of eyes can have donor sites re-epithelized with conjunctival cells at the periphery of the cornea. PMID- 22068850 TI - Postconceptional age at the treatment of retinopathy of prematurity in inborn and referred preterm infants from the same institution. AB - PURPOSE: The outcomes of the treatment of retinopathy of prematurity (ROP) seem to be better in inborn patients than in those patients who were referred for ROP treatment. This study aims to investigate the timing of treatment and the outcomes in inborn patients and in patients referred for treatment to the Hospital de Clinicas de Porto Alegre, Brazil. METHODS: An institutional prospective cohort study was conducted from 2002 to 2010 and included in group 1 all inborn preterm neonates treated for retinopathy of prematurity and in group 2 all babies referred for treatment to the same institution. All of the included patients presented birth weight (BW) <=1,500 g and/or gestational age (GA) <=32 weeks. Main outcomes were postconceptional age at the treatment and one year follow-up outcomes in both groups. The considered variables were: BW, GA, stage and location of retinopathy of prematurity at treatment. RESULTS: Group 1 comprised 24 inborn patients. Mean BW and GA at birth were 918 +/- 232 g and 28.2 +/- 2.1 weeks, respectively, and median post-conceptional postconceptional age at treatment was 37 weeks. Group 2 comprised 14 infants transferred for treatment. Mean BW and GA at birth were 885 +/- 188 g and 28.2 +/- 2.4 weeks, respectively, and median postconceptional age at treatment was 39 weeks. Mean BW and GA were similar in both groups (P=0.654 and P=0.949, respectively), but the difference among the postconceptional age was significant (P=0.029). CONCLUSIONS: Inborn patients were treated for retinopathy of prematurity during the 37(th) week of postconceptional age while transferred patients were treated, usually, after the 39(th) week postconceptional age. The worst outcomes observed among referred patients could be partially explained by the delayed time for treatment. PMID- 22068851 TI - [Ocular findings in children with congenital toxoplasmosis]. AB - PURPOSE: This study aimed to know the most common ocular findings in children with congenital toxoplasmosis. METHODS: This is a retrospective study carried out from a historical cohort, with a quantitative approach. We evaluated children referred to a pediatric infectious disease service and included only those with confirmed diagnosis of congenital toxoplasmosis. The ophthalmologic evaluation included regular fundus examination under pupil dilation. RESULTS: Of 58 children presumably exposed to risk of the disease during the pregnancy, 20 had ocular lesions during the first year of life (34 eyes). Of these, 12 were asymptomatic at birth. Strabismus was noted in 14 children (70%). In one child there was ptosis, and another had decrease in the palpebral fissure (microphthalmia). Retinochoroiditis was the most common complication, present in all 20 children. Seven children (35%) showed unilateral changes and 13 children showed bilateral changes (65%), with emphasis on the location in the posterior pole and macula. CONCLUSION: Retinochoroiditis and strabismus were outstanding as important sequelae of congenital toxoplasmosis. PMID- 22068852 TI - Real-time PCR in infectious uveitis as an alternative diagnosis. AB - PURPOSE: Uveitis is a major visual impairment disease affecting parts or the entire uveal tract and occasionally the sclera, the cornea or the optic nerve. The disease is a major cause of ocular morbidity and blindness in immunocompetent and immunocompromised patients. In this work we analyzed the sensitivity and specificity of real-time PCR to detect the etiological agent from blood, plasma, vitreous and aqueous humor and compared with the diagnostic hypothesis. METHODS: Twenty-seven patients (13 male) were studied and Real-time PCR method was used for the detection of herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV 2), varicella zoster virus (VZV), cytomegalovirus (CMV), Mycobacterium tuberculosis (TB) and Toxoplasma gondii (Toxo) in the aqueous humor as well as in the vitreous, blood and plasma. RESULTS: Our results showed the presence of Toxo, CMV, VZV or HSV-2 in 19.2% of aqueous humor samples, and in 30% of vitreous humor samples. In plasma and blood samples, only CMV was detected (11.1% and 3.7%, respectively). CONCLUSION: Real-time PCR was able to detect and to confirm diagnostic hypothesis in uveitis. Our data also confirms that vitreous humor is the best source for molecular diagnosis of infectious uveitis but indicates aqueous humor samples that are easier to obtain may also be appropriate to be tested by Real-time PCR. PMID- 22068853 TI - [Functional vision assessment in children with low vision from two to six years of age - a comparative study]. AB - PURPOSE: The Functional Vision Assessment (AVIF-2 to 6 years)'s capacity to differentiate visual ability levels in children with low vision was analyzed. The AVIF-2 to 6 years was created at the Infantile Low Vision Sector from Sao Geraldo Hospital, Brazil. METHODS: After a debate among professionals from different areas regarding the appropriateness of the test items, AVIF-2 to 6 years was applied to 40 children aged from 2 to 6 years; twenty children with low vision (Group 1) and twenty without it (Group 2) were assessed. Group 1 was recruited from the Infantile Low Vision Sector from Sao Geraldo Hospital. Group 2 comprised children from two different public day care centers and children were matched by age, gender and social level with group 1. Seven domains were studied: visual fixation, visual following, visual field confrontation, eye-hand coordination and surrounding locomotion, contrast vision and color vision discrimination. Group 1 children were submitted to a complete ophthalmologic exam and group 2 to ophthalmologic screening. Children with low vision and neurologic disease were excluded. Comparative analyzes were performed for both groups and for distinct subgroups classified by age (24 to 35 months, 36 to 59 months and 60 to 78 months) and by visual acuity subgroups (<1.0 logMAR and >=1.0 logMAR). RESULTS: The scores at total AVIF-2 to 6 years and its domains were statistically significant (p<0.05), except for the contrast vision and color vision discrimination domains. The total AVIF- 2 to 6 years median was lower for group 1 at the three interval ages. CONCLUSION: AVIF- 2 to 6 years can discriminate different levels of functional vision of low vision children, however the authors emphasize that although the results are encouraging, further studies shall be done until the test is ready for clinical use. PMID- 22068854 TI - [Surgical correction of permanent exotropia outcomes in amblyopic and non amblyopic patients]. AB - Permanent exotropia (XT) occurs in 1 to 2% of the pediatric population. Its management involves careful assessment of patient, treatment of amblyopia, refractive errors and surgery. The aim of the surgery is to straighten the eyes in the primary gaze position, giving a better cosmetic outcome. The factors reported to affect surgical outcome after exotropia surgery vary widely in reports and success rates for strabismus surgery have been reported to range from 60% to 80%. There are few reports to determine the relation between amblyopia and surgical outcome in exotropic patients. PURPOSE: To compare the surgical outcome of permanent exotropia surgery in amblyopic and non-amblyopic patients. METHODS: This is a retrospective study of 37 clinical records from amblyopic patients (Group A) and non-amblyopic patients (Group B) who underwent recess-resect in one eye for XT. Postoperative deviation was analyzed in one month (immediate) and in six months (final) in both groups and in between. Age: group A 24.7 +/- 14.2 years, group B 22.6 +/- 18.6 years; Preoperative deviation: group A 29.1 +/- 7.2(Delta), group B 28.4 +/- 6.8(Delta). RESULTS: The success rate in the immediate postoperative period was 60% (Group A) and 100% (Group B) (p<0.05); 50% (Group A) and 82.3% (Group B) (p=0.082) in the final postoperative period. There was a statistical difference in the immediate postoperative deviation, but the final deviation and the variation of the deviation were similar in both groups. CONCLUSION: There is a better outcome in patients of group B and no diference in the surgical outcome between these amblyopic and non-amblyopic patients in the final postoperative period. PMID- 22068855 TI - Health seeking behavior of the families of children with cataract attending an eye clinic in Rio de Janeiro, Brazil. AB - PURPOSE: To determine the health-seeking behavior of the families of children presenting with congenital and developmental cataract attending "Instituto Brasileiro de Oftalmologia" (IBOL), Rio de Janeiro, Brazil. METHODS: Caregivers of consecutive eligible children were interviewed using a pretested questionnaire and medical records were reviewed to collect information about their health seeking behavior and socioeconomic status in June and July of 2008. RESULTS: Data from 70 children were gathered, from which 42 (60.0%) had bilateral disease. Fifty-eight (82.9%) cases were considered congenital and 12 (17.1%) developmental. Presentation delay was observed in 33 (47.1%) children. Having insurance (adjusted OR 0.17; 95% CI 0.04 - 0.82) and being the only child (adjusted OR 0.16; 95% CI 0.04 - 0.69) decreased likelihood of late presentation. CONCLUSIONS: Delayed detection and presentation for treatment of non-traumatic pediatric cataract are still significant problems in the state of Rio de Janeiro. Early recognition as well as prompt referral and appropriate treatment have to be improved, especially at the public sector. PMID- 22068856 TI - [Study of retinopathy of prematurity in a university hospital]. AB - PURPOSE: To evaluate the prevalence of retinopathy of prematurity (ROP) in newborns, classify the cases, describe the risk factors for disease and treatment. METHODS: A retrospective observational cross-sectional study including newborns with gestational age <= 32 weeks and/or weight <= 1,500 g admitted to the neonatal intensive care unit of the Hospital de Clinicas, Universidade Federal de Uberlandia (HC-UFU) during the period of July 2005 to June 2007. RESULTS: We analyzed 148 patients. In 66 (44.6%) ROP was detected; 82 (55.4%) showed no disease. The statistically significant risk factors were: birth weight (p=0.0001), gestational age (p=0.0001), mechanical ventilation (p=0.0001), blood transfusion (p=0.0001), and postconceptional age (PCA) (p=0.0001). Of the 66 premature infants with ROP, 77% were treated medically (follow-up with indirect ophthalmoscopy) and 23% required surgical treatment or photocoagulation. CONCLUSION: Based on the data above, the prevalence observed in this study was high. The development of ROP was inversely proportional to the weight and gestational age at birth. PMID- 22068857 TI - Functional and cosmetic results of a lower eyelid crease approach for external dacryocystorhinostomy. AB - PURPOSE: External dacryocystorhinostomy is routinely performed through a cutaneous vertical incision placed on the lateral aspect of the nose. The lower eyelid crease approach has been seldom reported. The purpose of this study is to report the cosmetic and functional results of the lid crease approach for external dacryocystorhinostomy in a series of patients. METHODS: Prospective, interventional case series. Twenty-five consecutive patients (17 women) ranging in age from 3 to 85 years (mean +/- SD= 44.84 +/- 23.67) were included in the study. All patients but one underwent unilateral external dacryocystorhinostomy with a 10 to 15 mm horizontal incision placed on a subciliary relaxed eyelid tension line. The inner canthus was photographed with a Nikon D70S digital camera with a macrolens and resolution of 3008 x 2000 pixels at 1, 3 and 6 months after surgery. The resulting scar was judged from the photographs by 3 observers (ophthalmologist, plastic and head and neck surgeons) according to a four level scale (1= unapparent, 2= minimally visible, 3= moderately visible, 4= very visible). RESULTS: The surgery was easily performed in all patients with a 90.48% success. Three of the elderly patients (ages 61, 79 and 85 yr) developed mild lacrimal punctum ectropion, which resolved with conservative treatment. One patient had a hypometric blink which spontaneously recovered within one month. The mean score for scar visibility was 2.19 (1(st) mo), 1.65 (3(th) mo) and 1.44 (6(th) mo). CONCLUSIONS: The eyelid crease approach is an excellent option for external dacryocystorhinostomy. It leaves an unapparent scar since the first month after surgery, even in younger patients. The functional results are excellent and comparable to other techniques. Care should be taken in elderly patients with lower eyelid laxity in order to prevent lacrimal punctum ectropion. PMID- 22068858 TI - Danish type gelsolin-related amyloidosis in a Brazilian family: case reports. AB - Familial amyloidosis of the Finnish type (FAF) is an autosomal dominant form of systemic amyloidosis showing marked geographic clustering in Finland. The disease is caused by a point mutation, 654G-A, in the gelsolin gene. The Danish-subtype of FAF has been previously described in three families, the patients present clinical findings similar to FAF, and the mutation 654G-T in the gelsolin gene. Three members from two generations of the same family, with familial amyloidosis, were screened for mutations in the GSN gene. Genomic DNA was extracted from peripheral blood lymphocytes and the polymerase chain reaction (PCR) was carried out under standard conditions, using appropriate primers. Sequence analysis showed the presence of a G to T transition at nucleotide 654 of the gelsolin gene. This is the first report of gelsolin-related familial amyloidosis in a Brazilian family, and the result is particularly significant as this pedigree presents an unusual mutation, described previously in three families, with no known Finnish ancestors (Danish type). PMID- 22068859 TI - Intravitreal injection of ranibizumab for foveal-macular pattern dystrophy: case report. AB - In the recent years, anti-angiogenic medications have successfully treated other diseases associated with choroidal neovascularization. The anti-angiogenic therapy alone or combined with LASER and/or steroids has been effective in controlling ocular neovascularization, not only restricted to the treatment of typical membranes due to macular degeneration in the wet form. The discovery and subsequent use of these drugs has revolutionized medicine and ophthalmology. This report illustrates an example of successful treatment in a challenging pathology where it was found important visual and anatomical response after the use of ranibizumab. PMID- 22068860 TI - [Familial exudative vitreoretinopathy simulating Coats disease: case report]. AB - We report the case of a seven year-old male patient, born at term without any perinatal complications, referred to the Retina/Vitreous Service for diagnostic elucidation. He had a history of progressive visual acuity loss on his left eye that started four years ago. On examination, he had decreased corneal diameter and corectopia of the right eye (OD), without any noteworthy findings on the biomicroscopy of the left eye (OS). The fundus of the OD revealed total retinal detachment, and the OS initially showed peripheral retinal vascular abnormalities and retinal exudation, associated with retinal vitreous traction on the temporal sector. The CT and MRI of the brain/orbits showed no abnormalities, except for findings suggestive of an old retinal detachment on the OD, confirmed by ultrasonography, which also showed microphthalmia of the OD. The diagnosis of familial exudative vitreoretinopathy, a rare disease of autosomal dominant inheritance and related to consanguineous marriages, that can initially simulate Coats disease, was proposed. The patient was treated with diode laser photocoagulation in the temporal periphery of the OS, with improvement in the areas of vitreoretinal traction. PMID- 22068861 TI - [Perfluoro-n-octane in orbital cavity after posterior vitrectomy and suture of eye perforating injury: case report]. AB - A case of a perfluoro-n-octane leakage into the orbital cavity after corneoscleral suture, scleral buckling and pars plana vitrectomy in an eye with perforating injury after trauma is reported for the first time. A previously healthy 39-year-old man was sent for ophthalmic evaluation one day after suffering a penetrating ocular trauma in his right eye while hammering a nail. On the initial evaluation, the patient presented sudden reduction of visual acuity on his right eye with a perforating corneoscleral injury, intraocular foreign body and retinal detachment. The patient was submitted to corneoscleral suture, pars plana vitrectomy with perfluoro-n-octane administration to flatten the retina and scleral buckling, when it was found transfixation of the globe by the intraocular foreign body. Postoperatively, computed tomography scans of the orbit were ordered due to proptosis, which showed the presence of hyperdense images, suggesting leakage of perfluoro-n-octane into the orbital cavity. Thus, in cases of perforating eye injury, one should be suspicious about the possibility of intraocular foreign body, as well as possible occurrence of transfixation of the globe when scheduling the surgery. PMID- 22068862 TI - Meta-analysis of beta radiation augmentation for trabeculectomy - results in distinct ethnic groups. AB - PURPOSE: To conduct a systematic review with meta-analysis on the efficacy of trabeculectomy (TREC) followed by beta irradiation (BRT/TREC) compared to TREC alone for glaucoma in terms of intraocular pressure (IOP) control and adverse effects of treatment in different ethnic groups. METHODS: A meta-analysis of randomized controlled trials (RCT) was performed comparing adjunct BRT treatment for glaucoma with standard TREC after 12 months. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, Trial registers, bibliographic databases and recent studies of relevant journals were searched. Two reviewers independently reviewed relevant reports and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria. RESULTS: Of a total of 1,350 citations, eight studies (five cohorts, three randomized) were identified and only 3 RCT were included in this meta-analysis. Higher IOP reductions were verified in the BRT arm compared to the control arm (mean difference=1.68 mmHg, 95% CI= 0.61-2.68, P=0.002). Uncontrolled postoperative IOP (>21 mmHg) was less frequent when BRT was used (BRT/ TREC arm) compared to the control arm (38/218=17.4% versus 9/239=3.8%; OR=6.7; 95% CI 3.2-14.3, P<0.0001). Although better IOP control was observed in all patients treated with adjuvant BRT, only Black patients displayed a significant difference (P=0.005). There were no significant differences between the BRT and control arms regarding loss of visual acuity, postoperative complications and necessity of cataract surgery. CONCLUSION: Adjunct BRT increases the success rate of TREC, with better results in non Caucasian patients, and does not influence the occurrence of postoperative complications. PMID- 22068863 TI - Literature systematic review on the ophthalmological side effects of interferons. AB - Interferons alpha and beta have been used worldwide for a few decades, altering the natural history of several severe diseases including hepatitis C, cancer and immune-mediated conditions such as multiple sclerosis. The adverse events profile of interferons is well established, but only isolated reports of ophthalmological complications of interferon therapy have been published. The objective of this study was to carry out a literature systematic review on the subject, bringing to light the need for careful ophthalmological monitoring of patients undergoing interferon treatment. Nearly 500 cases of ophthalmological complications related to interferon have been reported. The most frequent findings were soft exudates, hemorrhages and retina ischemia. PMID- 22068865 TI - Relation between blood pressure and vascular events and mortality in patients with manifest vascular disease: J-curve revisited. AB - Recent studies have challenged the notion that "lower is better" for blood pressure in relation to vascular events and mortality in patients with vascular disease, whereas practice guidelines currently recommend to lower blood pressure to <130/80 mm Hg. We reassessed this J-curved relationship between blood pressure and cardiovascular events and all-cause mortality in patients with various manifestations of vascular disease. For this purpose, 5788 patients with symptomatic vascular disease enrolled in the Secondary Manifestations of Arterial Disease Study were followed-up for the occurrence of new vascular events (ie, myocardial infarction, stroke, or vascular death) and all-cause mortality. During a median of 5.0 years (interquartile range: 2.6-8.1 years), 788 patients experienced a new vascular event, and 779 died. Overall, the covariate-adjusted relationship between mean baseline systolic, diastolic, or pulse pressure and the occurrence of vascular events followed a J-curve with increased event rates above and below the nadir blood pressure of 143/82 mm Hg. A similar nonlinear relationship was found for diastolic pressure and all-cause mortality. Elevated blood pressure was not associated with increased morbidity and mortality in patients with recently diagnosed coronary artery disease, >=65 years, and having >60 mm Hg pulse pressure. Importantly, especially in these subgroups, low blood pressure could also be a symptom rather than a cause of disease. Blood pressure level below and above 143/82 mm Hg is, thus, an independent risk factor for recurrent events in patients with manifest vascular disease. Uncertainty of whether this association is causal provides a strong rationale for trials evaluating blood pressure treatment targets. PMID- 22068864 TI - Placental ischemia impairs middle cerebral artery myogenic responses in the pregnant rat. AB - One potential mechanism contributing to the increased risk for encephalopathies in women with preeclampsia is altered cerebral vascular autoregulation resulting from impaired myogenic tone. Whether placental ischemia, a commonly proposed initiator of preeclampsia, alters cerebral vascular function is unknown. This study tested the hypothesis that placental ischemia in pregnant rats (caused by reduced uterine perfusion pressure [RUPP]) leads to impaired myogenic responses in middle cerebral arteries. Mean arterial pressure was increased by RUPP (135+/ 3 mm Hg) compared with normal pregnant rats (103+/-2 mm Hg) and nonpregnant controls (116+/-1 mm Hg). Middle cerebral arteries from rats euthanized on gestation day 19 were assessed in a pressure arteriograph under active (+Ca(2+)) and passive (0 Ca(2+)) conditions, whereas luminal pressure was varied between 25 and 150 mm Hg. The slope of the relationship between tone and pressure in the middle cerebral artery was 0.08+/-0.01 in control rats and was similar in normal pregnant rats (0.05+/-0.01). In the RUPP model of placental ischemia, this relationship was markedly reduced (slope=0.01+/-0.00; P<0.05). Endothelial dependent and independent dilation was not different between groups, nor was there evidence of vascular remodeling assessed by the wall:lumen ratio and calculated wall stress. The impaired myogenic response was associated with brain edema measured by percentage of water content (RUPP P<0.05 versus control and normal pregnant rats). This study demonstrates that placental ischemia in pregnant rats leads to impaired myogenic tone in the middle cerebral arteries and that the RUPP model is a potentially important tool to examine mechanisms leading to encephalopathy during preeclamptic pregnancies. PMID- 22068867 TI - Carotid stiffness in young adults: a life-course analysis of its early determinants: the Amsterdam Growth and Health Longitudinal Study. AB - Cardiovascular risk factors affecting arterial stiffness in adulthood may develop at different critical periods earlier in life. We examined whether the trajectories, from adolescence to young adulthood, of blood pressure, body fatness and fat distribution, blood lipids, cardiorespiratory fitness, and heart rate determined levels of arterial stiffness in young adults. We investigated 373 apparently healthy adults in whom cardiovascular risk factors were repeatedly examined between the ages of 13 and 36 years and carotid stiffness estimates were obtained at the age of 36 years. Differences in the mean levels and the trajectories of risk factors throughout the 24-year longitudinal period between subjects with different levels of carotid stiffness at age 36 years were analyzed with generalized estimating equations. Compared with individuals with less stiff carotid arteries, those with stiffer carotid arteries at the age of 36 years were characterized from ages 13 to 36 years by greater levels of and steeper increases in blood pressure and central fatness, independently of each other and other risk factors. These increases were already present in adolescence, preceded the development of poorer levels of blood lipids, cardiorespiratory fitness, and heart rate, which were evident during adulthood only, and explained to a great extent the deleterious association between these risk factors and carotid stiffness at the age of 36 years. Multiple and intertwined mechanisms involved in the pathogenesis of arterial stiffness have their origins in early life. Blood pressure and central fatness have a pivotal role herein and should be specifically targeted to prevent arterial stiffening and its cardiovascular sequelae. PMID- 22068866 TI - Left ventricular mass and function with reduced-fat or reduced-carbohydrate hypocaloric diets in overweight and obese subjects. AB - In animals, carbohydrate and fat composition during dietary interventions influenced cardiac metabolism, structure, and function. Because reduced carbohydrate and reduced-fat hypocaloric diets are commonly used in the treatment of obesity, we investigated whether these interventions differentially affect left ventricular mass, cardiac function, and blood pressure. We randomized 170 overweight and obese subjects (body mass index, 32.9+/-4.4; range, 26.5-45.4 kg/m(2)) to 6-month hypocaloric diets with either reduced carbohydrate intake or reduced fat intake. We obtained cardiac MRI and ambulatory blood pressure recordings over 24 hours before and after 6 months. Ninety subjects completing the intervention period had a full cardiac MRI data set. Subjects lost 7.3+/-4.0 kg (7.9+/-3.8%) with reduced-carbohydrate diet and 6.2+/-4.2 kg (6.7+/-4.4%) with reduced-fat diet (P<0.001 within each group; P=not significant between interventions). Caloric restriction led to similar significant decreases in left ventricular mass with low-carbohydrate diets (5.4+/-5.4 g) or low-fat diets (5.2+/-4.8 g; P<0.001 within each group; P=not significant between interventions). Systolic and diastolic left ventricular function did not change with either diet. The 24-hour systolic blood pressure decreased similarly with both interventions. Body weight change (beta=0.33; P=0.02) and percentage of ingested n-3 polyunsaturated fatty acids (beta=-0.27; P=0.03) predicted changes in left ventricular mass. In conclusion, weight loss induced by reduced-fat diets or reduced-carbohydrate diets similarly improved left ventricular mass in overweight and obese subjects over a 6-month period. However, n-3 polyunsaturated fatty acid ingestion may have an independent beneficial effect on left ventricular mass. PMID- 22068868 TI - Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. AB - Angiotensin II-induced cardiac damage is associated with oxidative stress dependent mitochondrial dysfunction. Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs. CR ameliorated angiotensin II-induced cardiomyocyte hypertrophy, vascular inflammation, cardiac damage and fibrosis, cardiomyocyte apoptosis, and cardiac atrial natriuretic peptide mRNA overexpression. The effects were blood pressure independent and were linked to increased endoplasmic reticulum stress, autophagy, serum adiponectin level, and 5' AMP-activated protein kinase phosphorylation. CR decreased cardiac p38 phosphorylation, nitrotyrosine expression, and serum insulin-like growth factor 1 levels. Mitochondria from dTGR hearts showed clustered mitochondrial patterns, decreased numbers, and volume fractions but increased trans-sectional areas. All of these effects were reduced in CR dTGRs. Mitochondrial proteomic profiling identified 43 dTGR proteins and 42 Sprague-Dawley proteins, of which 29 proteins were in common in response to CR. We identified 7 proteins in CR dTGRs that were not found in control dTGRs. In contrast, 6 mitochondrial proteins were identified from dTGRs that were not detected in any other group. Gene ontology annotations with the Panther protein classification system revealed downregulation of cytoskeletal proteins and enzyme modulators and upregulation of oxidoreductase activity in dTGRs. CR provides powerful, blood pressure-independent, protection against angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. The findings support the notion of modulating cardiac bioenergetics to ameliorate angiotensin II-induced cardiovascular complications. PMID- 22068870 TI - Plasma aldosterone levels and development of insulin resistance: prospective study in a general population. AB - Aldosterone plays a role in hypertension, and hypertension is prevalent in patients with insulin resistance. Cross-sectional studies have reported that plasma aldosterone levels are higher in patients with insulin resistance. However, it is not known whether plasma aldosterone levels predict the development of insulin resistance. Subjects of the present study were 1235 local residents (490 men and 745 women) who participated in health screenings in Japan in 1999. Plasma aldosterone levels were measured by radioimmunoassay. We investigated the cross-sectional relationship between plasma aldosterone levels and insulin resistance (homeostasis model assessment index >=1.73 according to the diagnostic criteria used in Japan) in 1088 nondiabetic participants. At the 10-year follow-up, 141 subjects had died, and 260 subjects refused re examination. We performed a prospective analysis of 564 subjects to predict incident insulin resistance. We found a significant (P<0.001) cross-sectional relationship between plasma aldosterone and homeostasis model assessment index at baseline. In the prospective analysis, a significantly higher (P<0.05) relative risk (1.71 [95% CI: 1.03-2.84]) was observed in the highest tertile versus lowest tertile of plasma aldosterone for the development of insulin resistance, after adjustment for confounding factors. This 10-year prospective study demonstrated that plasma aldosterone levels predicted the development of insulin resistance in a general population. PMID- 22068873 TI - The J-shaped curve in secondary prevention: shall clinical practice change? PMID- 22068872 TI - Vascular biomarkers in the prediction of clinical cardiovascular disease: the Strong Heart Study. AB - We compared the ability of separately measured intimal-medial thickness and atherosclerotic plaque to predict incident cardiovascular disease. American Indian men and women from the Strong Heart Study who were free of cardiovascular disease were evaluated with carotid ultrasound and cardiovascular disease risk factor assessment. End-diastolic intimal-medial thickness of the common carotid arteries was measured and averaged. Arterial mass (cross-sectional area) was calculated from intimal-medial thickness and end-diastolic diameter. Atherosclerosis was defined by focal plaque (discrete thickening >50% relative to the adjacent wall) and the number of carotid segments containing plaque (plaque score); 2441 participants (age 63+/-8 years) were followed-up for a mean of 7.7+/ 2.8 years, during which time 495 experienced incident cardiovascular disease events. Time-to-event analyses were performed in groups stratified according to diabetes and hypertension status. Cardiovascular disease events were predicted by presence and extent of atherosclerosis in all groups; intima-medial thickness and arterial mass were only associated with outcomes when neither hypertension nor diabetes was present. Unequivocal evidence of atherosclerosis (plaque) and its extent (plaque score) are independently associated with incident cardiovascular disease events in individuals without preexisting cardiovascular disease regardless of diabetes and hypertension status. Hypertension-related increases in intima-media thickness and arterial mass appear to limit their use as measures of early or diffuse atherosclerosis and, hence, association with cardiovascular disease outcomes. These findings support the utility of separate assessment of focal atherosclerosis and intimal-medial thickness in epidemiological studies, trials, and risk stratification protocols. PMID- 22068871 TI - Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study. AB - Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD >=20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH >=65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease. PMID- 22068874 TI - A loss-of-function polymorphism in the human P2X4 receptor is associated with increased pulse pressure. AB - The P2X4 receptor is involved in endothelium-dependent changes in large arterial tone in response to shear stress and is, therefore, potentially relevant to arterial compliance and pulse pressure. Four identified nonsynonymous polymorphisms in P2RX4 were reproduced in recombinantly expressed human P2X4. Electrophysiological studies showed that one of these, the Tyr315>Cys mutation (rs28360472), significantly reduced the peak amplitude of the ATP-induced inward current to 10.9% of wild-type P2X4 receptors in transfected HEK-293 cells (10 MUmol/L of ATP; n=4-8 cells; P<0.001). Concentration-response curves for ATP and the partial agonist BzATP demonstrate that the 315Cys-P2X4 mutant had an increased EC(50) value for both ligands. Mutation of Tyr315>Cys likely disrupts the agonist binding site of P2X4 receptors, a finding supported by molecular modeling based on the zebrafish P2X4 receptor crystal structure. We tested inheritance of rs28360472 encoding the Tyr315>Cys mutation in P2RX4 against pulse pressure in 2874 subjects from the Victorian Family Heart Study. The minor allele frequency was 0.014 (1.4%). In a variance components analysis we found significant association with pulse pressure (P=0.023 for total association) where 1 minor allele increased pulse pressure by 2.84 mm Hg (95% CI: 0.41-5.27). This increase in pulse pressure associated with inheritance of 315Cys-P2X4 receptors might reflect reduced large arterial compliance as a result of impaired endothelium-dependent vasodilation in large arteries. PMID- 22068876 TI - Supramolecular hybrid of metal nanoparticles and semiconducting single-walled carbon nanotubes wrapped by a fluorene-carbazole copolymer. AB - The first approach for the preparation of metal nanoparticle/semiconducting single-walled carbon nanotube (SWNT) hybrids with specified chirality is described. For this purpose, a copolymer of a fluorene derivative with two long chain alkyl substituents and a carbazole derivative carrying a thiol group was used. The copolymer was found to selectively dissolve (7,6)- and (8,7)SWNTs, as determined by UV/Vis/NIR absorption and Raman spectroscopy and 2D photoluminescence mapping. Gold and silver nanoparticles with diameters of about 3.8 and about 3.2 nm, respectively, were readily attached along the SWNTs by means of coordination bonds between the nanoparticles and the thiol moieties on the copolymer, as revealed by atomic force and electron microscopy studies. The study provides a novel way to design and fabricate metal nanoparticle/semiconducting SWNT hybrids with specific nanotube chirality. PMID- 22068877 TI - Dendritic nanospace constructed by only glycerol units enhanced uptake of a fluorescent molecule in aqueous solution. AB - A polyglycerol dendrimer (PGD) of generation 2, which consists of only glycerol units, constructed nanospace capable of uptake of a fluorescent molecule with a 1:1 stoichiometry. On the other hand, a PGD of generation 1 trapped the molecule at the outer part. PMID- 22068875 TI - Interleukin 6 underlies angiotensin II-induced hypertension and chronic renal damage. AB - Chronic kidney disease (CKD) is a prevalent life-threatening disease frequently associated with hypertension, progression to renal fibrosis, and eventual renal failure. Although the pathogenesis of CKD remains largely unknown, an increased inflammatory response is known to be associated with the disease and has long been speculated to contribute to disease development. However, the causative factors, the exact role of the increased inflammatory cascade in CKD, and the underlying mechanisms for its progression remain unidentified. Here we report that interleukin 6 (IL-6) expression levels were significantly increased in the kidneys collected from CKD patients and further elevated in CKD patients characterized with hypertension. Functionally, we determined that angiotensin II is a causative factor responsible for IL-6 induction in the mouse kidney and that genetic deletion of IL-6 significantly reduced hypertension and key features of CKD, including renal injury and progression to renal fibrosis in angiotensin II infused mice. Mechanistically, we provide both human and mouse evidence that IL-6 is a key cytokine functioning downstream of angiotensin II signaling to directly induce fibrotic gene expression and preproendothelin 1 mRNA expression in the kidney. Overall, both the mouse and human studies reported here provide evidence that angiotensin II induces IL-6 production in the kidney, and that, in addition to its role in hypertension, increased IL-6 may play an important pathogenic role in CKD by inducing fibrotic gene expression and ET-1 gene expression. These findings immediately suggest that the IL-6 signaling is a novel therapeutic target to manage this devastating disorder affecting millions worldwide. PMID- 22068878 TI - Risk factors for missed HIV primary care visits among men who have sex with men. AB - Benefits of anti-retroviral therapy (ART) depend on consistent HIV care attendance. However, appointment non-adherence (i.e. missed appointments) is common even in programs that reduce financial barriers. Demographic, health/treatment, and psychosocial contributors to appointment non-adherence were examined among men who have sex with men (MSM) attending HIV primary care. Participants (n = 503) completed questionnaires, and HIV biomarker data were extracted from medical records. At 12 months, records were reviewed to assess HIV primary care appointment non-adherence. Among MSM, 31.2% missed without cancellation at least one appointment during 12-month study period. Independent predictors (P < 0.05) were: low income (OR = 1.87); African American (OR = 3.00) and Hispanic/Latino (OR = 4.31) relative to non-Hispanic White; depression (OR = 2.01); and low expectancy for appointments to prevent/treat infection (OR = 2.38), whereas private insurance (OR = 0.48) and older age (OR = 0.94) predicted lower risk. Low self-efficacy predicted marginal risk (OR = 2.74, P = 0.10). The following did not independently predict risk for non-adherence: education, relationship status, general health, time since HIV diagnosis, ART history, post traumatic stress disorder, HIV stigma, or supportive clinic staff. Appointment non-adherence is prevalent, particularly among younger and racial/ethnic minority MSM. Socioeconomic barriers, depression and low appointment expectancy and self efficacy may be targets to increase care engagement. PMID- 22068879 TI - The benefits of cognitive training after a coronary artery bypass graft surgery. AB - Cognitive deficits are frequent after coronary artery bypass graft surgery (CABG) in the elderly population. In fact, memory and attention deficits can persist several months after the surgery. Recent studies with healthy older adults have shown that memory and attention can be improved through cognitive training programs. The present study examined whether memory training (method of loci and story generation) and attentional training (dual-task computerized training) could improve cognitive functions in patients aged 65 years and older who underwent CABG surgery. Participants (n = 51) were assigned to one of three groups: (1) control group (tested at 1, 3 and 6 months after the surgery), (2) attention training followed by memory training, (3) memory training followed by attention training (groups 2 and 3: tested at 1, 2, 3 and 6 months after the surgery). The trainings took place between the 6th and 10th week following the surgery. The three groups were compared before and after each training program using attention and memory tests and neuropsychological tests. The results showed that attention and memory trainings lead to significant improvement in the cognitive domain that was trained. It thus seems that cognitive training can be a promising tool to enhance cognitive functions after a CABG surgery. PMID- 22068880 TI - Endarterectomy versus carotid stenting. PMID- 22068882 TI - Characterization of the necrosis determinant of the European genotype of pepino mosaic virus by site-specific mutagenesis of an infectious cDNA clone. AB - Mild and necrotic isolates have been described for the European (EU) genotype of pepino mosaic virus (PepMV), an important pathogen of tomato worldwide. In this study, we produced various infectious cDNA clones of an EU isolate with point mutations introduced by site-directed mutagenesis. Our results showed that the genetic determinant responsible for necrosis induction on tomato and Datura inoxia was amino acid 67 of TGBp3. This amino acid residue also acts as necrosis determinant in PepMV isolates belonging to the Chilean 2 genotype. This demonstrates that a single point mutation plays a role in necrosis induction by PepMV, irrespective of genotype. PMID- 22068881 TI - Characterization of avian influenza viruses isolated from domestic ducks in Vietnam in 2009 and 2010. AB - In the surveillance of avian influenza in Vietnam, 26 H9N2, 1 H3N2, 1 H3N8, 7 H4N6, 3 H11N3, and 1 H11N9 viruses were isolated from tracheal and cloacal swab samples of 300 domestic ducks in April 2009, and 1 H9N6 virus from 300 bird samples in March 2010. Out of the 27 H9 virus isolates, the hemagglutinins of 18 strains were genetically classified as belonging to the sublineage G1, and the other nine belonged to the Korean sublineage. Phylogenetic analysis revealed that one of the 27 H9 viruses was a reassortant in which the PB2 gene belonged to the Korean sublineage and the other seven genes belonged to the G1 sublineage. Three representative H9N2 viruses were intranasally inoculated into ducks, chickens, pigs, and mice. On the basis of experimental infection studies, it was found that each of the three viruses readily infected pigs and replicated in their upper respiratory tracts, and they infected chickens with slight replication. Viruses were recovered from the lungs of mice inoculated with two of the three isolates. The present results reveal that H9 avian influenza viruses are prevailing and genetic reassortment occurs among domestic ducks in Vietnam. It is recommended that careful surveillance of swine influenza with H9 viruses should be performed to prepare for pandemic influenza. PMID- 22068883 TI - Oxovanadium(IV) based hypocrellin B complexes with enhanced photodynamic activity. AB - Hypocrellin B (HB), a naturally occurring photosensitizer, has been extensively and intensively studied as a promising photodynamic therapy (PDT) agent. In this work, three new oxovanadium(IV) complexes were designed and synthesized with HB as a bridging ligand and phen (1,10-phenanthroline, complex 1), tmp (3,4,7,8 tetramethyl-1,10-phenanthroline, complex 2) and dpq (dipyrido[3,2-f:2'3' h]quinoxaline, complex 3) as terminal ligands. The use of a diimine terminal ligand avoids the formation of polymeric complexes and ensures the three VO(2+) HB complexes possess a definite molecular formula and molecular weight to meet the single component requirement for an ideal PDT agent. Compared to HB, the VO(2+)-HB complexes exhibit improved water solubility, enhanced absorptivity in the phototherapeutic window, increased binding affinity toward dsDNA, and similar singlet oxygen quantum yield, therefore advanced DNA photocleavage activity. Both the DNA binding constants and photo nuclease activities of the complexes follow the order 2 (tmp) > 3 (dpq) > 1 (phen), demonstrating the importance of the binding affinity to biomolecules, which improves the bioavailability of reactive oxygen species. Our work opens a new avenue for the development of HB-based PDT agents. PMID- 22068884 TI - Hazard analysis and risk assessment in the development of biomedical drug formulation equipment. AB - Hazard analysis and risk assessment techniques are utilized within many private sector industries and government agencies, including the medical device and pharmaceutical industry, within a structured process to control human injuries and environmental and property damage. In the U.S. the Federal Drug Administration (FDA) requires a hazard analysis be performed on all medical devices. While there are biomedical engineering applications reported which deal with human hazards in clinical, patient care environment, no previous studies extend these traditional techniques to a university-based, research environment. This study applies a tiered approach to hazard analysis and risk assessment to a biomedical, university-based, research environment in the design of a high throughput platform that screens chemical excipients (additives) for their ability to increase protein solubility. Each design stage (conceptual, preliminary, system, and detailed) requires a unique hazard analysis technique based on available information. The analysis techniques applied here are evaluated for their use in a biomedical research environment where experiment accuracy is a primary concern. PMID- 22068885 TI - Assessment of obstructive sleep apnea and its severity during wakefulness. AB - In this article, a novel technique for assessment of obstructive sleep apnea (OSA) during wakefulness is proposed; the technique is based on tracheal breath sound analysis of normal breathing in upright sitting and supine body positions. We recorded tracheal breath sounds of 17 non-apneic individuals and 35 people with various degrees of severity of OSA in supine and upright sitting positions during both nose and mouth breathing at medium flow rate. We calculated the power spectrum, Kurtosis, and Katz fractal dimensions of the recorded signals and used the one-way analysis of variance to select the features, which were statistically significant between the groups. Then, the maximum relevancy minimum redundancy method was used to reduce the number of characteristic features to two. Using the best two selected features, we classified the participant into severe OSA and non OSA groups as well as non-OSA or mild vs. moderate and severe OSA groups; the results showed more than 91 and 83% accuracy; 85 and 81% specificity; 92 and 95% sensitivity, for the two types of classification, respectively. The results are encouraging for identifying people with OSA and also prediction of OSA severity. Once verified on a larger population, the proposed method offers a simple and non invasive screening tool for prediction of OSA during wakefulness. PMID- 22068887 TI - Diffusion-weighted whole-body MRI with background body signal suppression: technical improvements at 3.0 T. AB - PURPOSE: To improve image quality of diffusion-weighted body magnetic resonance imaging (MRI) with background body signal suppression (DWIBS) at 3.0 T. MATERIALS AND METHODS: In 30 patients and eight volunteers, a diffusion-weighted spin-echo echo-planar imaging sequence with short TI inversion recovery (STIR) fat suppression was applied and repeated using slice-selective gradient reversal (SSGR) and/or dual-source parallel radiofrequency (RF) transmission (TX). The quality of diffusion-weighted images and gray scale inverted maximum intensity projections (MIP) were visually assessed by intraindividual comparison with respect to the level of fat suppression and signal homogeneity. Moreover, the contrast between lesions/lymph nodes and background (C(lb)) was analyzed in the MIP reconstructions. RESULTS: By combining STIR with SSGR, fat suppression was significantly improved (P < 0.001) and C(lb) was increased two times. The use of TX allowed the reduction of acquisition time and improved image quality with regard to signal homogeneity (P < 0.001) and fat suppression (P = 0.005). CONCLUSION: DWIBS at 3.0 T can be improved by using SSGR and TX. PMID- 22068886 TI - Glycoengineering of HCELL, the human bone marrow homing receptor: sweetly programming cell migration. AB - The successful clinical implementation of adoptive cell therapeutics, including bone marrow transplantation and other stem cell-based treatments, depends critically on the ability to deliver cells to sites where they are needed. E selectin, an endothelial C-type lectin, binds sialofucosylated carbohydrate determinants on its pertinent ligands. This molecule is expressed in a constitutive manner on bone marrow and dermal microvascular endothelium, and inducibly on post-capillary venules at all sites of tissue injury. Engagement of E-selectin with relevant ligand(s) expressed on circulating cells mediates initial "tethering/rolling" endothelial adhesive interactions prerequisite for extravasation of blood-borne cells at any target tissue. Most mammalian cells express high levels of a transmembrane glycoprotein known as CD44. A specialized glycoform of CD44 called "Hematopoietic Cell E-/L-selectin Ligand" (HCELL) is a potent E-selectin ligand expressed on human cells. Under native conditions, HCELL expression is restricted to human hematopoietic stem/progenitor cells. We have developed a technology called "Glycosyltransferase-Programmed Stereosubstitution" (GPS) for custom-modifying CD44 glycans to create HCELL on the surface of living cells. GPS-based glycoengineering of HCELL endows cell migration to endothelial beds expressing E-selectin. Enforced HCELL expression targets human mesenchymal stem cell homing to marrow, licensing transendothelial migration without chemokine signaling via a VLA-4/VCAM-1-dependent "Step 2-bypass pathway." This review presents an historical framework of the homing receptor concept, and will describe the discovery of HCELL, its function as the bone marrow homing receptor, and how enforced expression of this molecule via chemical engineering of CD44 glycans could enable stem cell-based regenerative medicine and other adoptive cell therapeutics. PMID- 22068889 TI - Endoscopic ultrasound-guided treatment of bleeding duodenal varix. AB - A 35-year-old man presented with recurrence of upper gastrointestinal bleed after eradication of esophageal varices. Upper gastrointestinal endoscopy revealed submucosal lesion in the duodenum and endoscopic ultrasound (EUS) demonstrated it to be a duodenal varix. Cyanoacrylate glue was injected into the duodenal varix and successful obliteration of the duodenal varix was demonstrated on a follow up EUS. PMID- 22068888 TI - The IgE gene in primates exhibits extraordinary evolutionary diversity. AB - Membrane-bound IgE (mIgE) on B lymphocytes is essential for IgE production. Earlier studies showed that the epsilon chain of mIgE (mepsilon) on human B cells has a "long" isoform, with an extra "CepsilonmX" domain of 52 amino acid (aa) residues between the CH4 domain and the membrane-anchor segment, as compared to the conventional "short" isoform. Because CepsilonmX provides an antigenic site for targeting IgE-expressing B cells to down-regulate IgE production in patients with allergy, analysis of CepsilonmX in various animals is of great interest. Hence, we analyzed the epsilon Ig gene, in particular, its membrane exon regions encoding the membrane anchor peptide segment and CepsilonmX domain, of 26 species of the order Primates and 12 species of seven non-Primate orders using data obtained experimentally or retrieved from GenBank. Our analyses reveal the unexpected finding that the genes of three extant tarsier species do not contain the membrane exons for mIgE. Another striking finding is that early evolved Strepsirhini primates such as lemurs and lorises do not have gene segments for the long isoform, whereas New World monkeys such as marmosets and squirrel monkeys allow the transcription of only the long isoform. In Old World monkeys and apes, including humans, the epsilon gene allows the transcription of both isoforms. This work thus reveals the dramatic differences in the gene segment encoding the mepsilon C terminal region among the four major primate lineages: the Strepsirhini primates, the tarsiers, New World monkeys, and Old World monkeys and apes/humans. PMID- 22068890 TI - Biomass fuel use for cooking in Sri Lanka: analysis of data from national demographic health surveys. AB - BACKGROUND: Biomass cooking fuel is the main source of indoor air pollution in the majority of households in the developing world. Sri Lanka is an island of about 20 million population with urban, rural, and estate population of 14.6%, 80.0%, and 5.4%, respectively. This study describes biomass fuel use for cooking in Sri Lanka. METHODS: We analyzed data from two national Demographic Health Surveys (2000 and 2007) to identify the use and determinants of cooking fuels in Sri Lankan households. The results are based on a sample of 8,169 households in 2000 and 19,862 households in 2007. RESULTS: Wood was the principal cooking fuel used in 78.3% and 78.5% of households in 2000 and 2007, respectively. In 2007, 96.3% of estate sector households used firewood as compared to 84.2% in the rural and 34.6% in the urban sectors. Similar trends were noted in 2000 as well. CONCLUSIONS: The shift from firewood to cleaner fuels in Sri Lanka is negligible from 2000 to 2007. Improving the quality of life of the population does not necessarily predict a shift towards the use of cleaner cooking fuels in Sri Lanka. PMID- 22068891 TI - Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients. AB - Colorectal cancer remains a major cause of cancer mortality in the Western world. With a median age at presentation of 71, patients with metastatic disease are often elderly with significant co-morbidities. In addition, elderly patients are more likely to be undertreated and under-represented in clinical trials. Therefore, as the available data from clinical trials are scarce, the optimal treatment strategy for this group of patients has not been adequately defined. In the setting of metastatic colorectal cancer, the introduction of so called targeted agents has significantly improved outcomes in the context of randomized clinical trials, while at the same time increasing treatment options for such patients. This review focuses on the role of targeted therapies in elderly patients with metastatic colorectal cancer, with specific reference to toxicity and tolerability. It should be noted that studies reviewed herein will have mostly included fit elderly patients fulfilling specific inclusion criteria. The available data so far are limited but suggest that targeted agents have similar efficacy and tolerability in elderly fit patients when compared with younger ones, provided caution is exercised in specific high-risk sub-groups. Clearly, further studies aimed at this specific patient population using well-established geriatric end-points will hopefully identify those patients more likely to benefit and less likely to suffer severe side effects. PMID- 22068893 TI - Updated practice guideline for somatostatin receptor scintigraphy. PMID- 22068892 TI - Vitamin D, osteocalcin, and risk for adiposity as comorbidities in middle school children. AB - Nonclassic actions of vitamin D include potential regulation of immune function and glucose homeostasis. The bone-metabolism loop has recently been expanded to include osteocalcin, which appears to play a more direct role in pancreatic beta cell function and energy metabolism. We hypothesized that both vitamin D and osteocalcin would correlate negatively with indices of adiposity-related comorbidity risk in periadolescents, varying by ethnic group. We analyzed anthropometric, metabolic, and inflammatory markers from a multiethnic population of 106 school children 11 to 14 years of age studied as part of the Reduce Obesity and Diabetes (ROAD) consortium. As expected, 25-hydroxyvitamin D (25-OH vitamin D) was inversely correlated with intact parathyroid hormone (iPTH); total osteocalcin (OCN) and uncarboxylated osteocalcin (uOCN) were directly correlated with each other. OCN and uOCN concentrations correlated inversely with age. Vitamin D deficiency was most prevalent among East Asians (EA) and African Americans (AA). The highest lipid risk scores and homeostatic model for assessment of insulin resistance (HOMA-IR) values were seen in the South Asian (SA) group. Overall, adiposity measures were inversely correlated with OCN and iPTH, whereas such relationships were not observed for vitamin D. Acute insulin response to glucose challenge correlated negatively with uOCN in all subjects; however, lipid risk score correlated negatively with uOCN only in whites. The relationships between markers of calcium metabolism and body composition, glucose homeostasis, lipids, and inflammation all showed racial and ethnic differences. No consistent relationship was found between vitamin D and adiposity or vitamin D and glucose metabolism; instead vitamin D levels varied by race and ethnicity in this school-based group. These findings are consistent with the hypothesis that markers of calcium and bone metabolism may reflect risk for adiposity-related comorbidities in children. PMID- 22068894 TI - Clinical feasibility of fast 3-dimensional dosimetry of the liver for treatment planning of hepatocellular carcinoma with 90Y-microspheres. AB - Several treatment strategies are used for selective internal radiation therapy with (90)Y-microspheres. The diversity of approaches does not favor the standardization of the prescribed activity calculation. To this aim, a fast 3 dimensional (3D) dosimetry method was developed for (90)Y-microsphere treatment planning and was clinically evaluated retrospectively. METHODS: Our 3D approach is based on voxel S values (VSVs) and has been implemented in the software tool VoxelDose. VSVs were previously calculated at a fine voxel size. The time integrated activity (TIA) map is derived from pretherapeutic (99m)Tc macroaggregated-albumin SPECT/CT. The fine VSV map is resampled at the voxel size of the TIA map. Then, the TIA map is convolved with the resampled VSV map to construct the 3D dose map. Data for 10 patients with 12 tumor sites treated by (90)Y-microspheres for hepatocellular carcinoma were collected retrospectively. 3D dose maps were computed for each patient, and tumoral liver and nontumoral liver (TL and NTL, respectively) were delineated, allowing the computation of descriptive statistics (i.e., mean absorbed dose, minimum absorbed dose, and maximum absorbed dose) and dose-volume histograms. Mean absorbed doses in TL and NTL from VoxelDose were compared with those calculated with the standard partition model. RESULTS: The estimated processing time for a complete 3D dosimetry calculation is on the order of 15 min, including 10 s for the dose calculation (i.e., VSV resampling and convolution). An additional 45 min was needed for the semiautomatic and manual segmentation of TL and NTL. The mean absorbed dose (+/-SD) was 422 +/- 263 Gy for TL and 50.1 +/- 36.0 Gy for NTL. The comparison between VoxelDose and partition model shows a mean relative difference of 1.5% for TL and 4.4% for NTL. Results show a wide spread of voxel-dose values around mean absorbed dose. The minimum absorbed dose within TL ranges from 32 to 267 Gy (n = 12). The fraction of NTL volume irradiated with at least 80 Gy ranges from 4% to 70% (n = 10), and the absorbed dose from which 25% of NTL was the least irradiated ranges from 14 to 178 Gy. CONCLUSION: This article demonstrates the feasibility of a fast 3D dosimetry method for (90)Y-microspheres and highlights the potential value of a 3D treatment planning strategy. PMID- 22068895 TI - 124I-huA33 antibody uptake is driven by A33 antigen concentration in tissues from colorectal cancer patients imaged by immuno-PET. AB - The primary aim of this analysis was to examine the quantitative features of antibody-antigen interactions in tumors and normal tissue after parenteral administration of antitumor antibodies to human patients. METHODS: Humanized anti A33 antibody (10 mg) labeled with the positron-emitting radionuclide (124)I ((124)I-huA33) was injected intravenously in 15 patients with colorectal cancer. Clinical PET/CT was performed approximately 1 wk later, followed by a detailed assay of surgically removed tissue specimens including radioactivity counting, autoradiography, immunohistochemistry, and antigen density determination. RESULTS: PET/CT showed high levels of antibody targeting in tumors and normal bowel. In tissue specimens, the spatial distribution of (124)I-huA33 conformed to that of A33 antigen, and there was a linear relationship between the amount of bound antibody and antigen concentration. Antibody uptake was high in 1- to 2-mm regions of antigen-positive tumor cells (mean, ~0.05 percentage injected dose per gram) and in antigen-positive normal colonic mucosa (mean, ~0.03 percentage injected dose per gram). The estimated binding site occupancy for tumor and normal colon was 20%-50%. CONCLUSION: The in vivo biodistribution of (124)I-huA33 in human patients 1 wk after antibody administration was determined by A33 antigen expression. Our data imply that the optimal strategy for A33-based radioimmunotherapy of colon cancer will consist of a multistep treatment using a radionuclide with short-range (alpha- or beta-particle) emissions. PMID- 22068896 TI - "Treadmill exercise does not affect image quality on subsequent whole body FDG PET scan". PMID- 22068897 TI - Antitumor effects of a human dimeric antibody fragment 131I-AFRA-DFM5.3 in a mouse model for ovarian cancer. AB - AFRA-DMF5.3 is a human antibody fragment that, as a dimer, specifically binds to the alpha-folate receptor (FR) on ovary cancer cells. Pharmacokinetic and biodistribution parameters of (131)I-AFRA-DFM5.3 after intravenous administration in animal models support its potential therapeutic use. We evaluated its preclinical specificity and therapeutic efficacy in tumor models. METHODS: A negative control, AFRA-DFM6.1, was obtained by protein engineering. The activity and specificity of (131)I-AFRA-DFMs were evaluated by systemic administration (intravenous) in subcutaneous tumor xenograft-bearing nude mice. Pharmacokinetics, biodistribution, and efficacy were assessed by intraperitoneal administration of (131)I-AFRA-DFM5.3 in nude mice bearing 2 different intraperitoneal ovarian carcinoma xenografts. Treatments were tested at different doses and as single or double administrations 1 wk apart. RESULTS: In subcutaneous models, (131)I-AFRA-DFM5.3, but not the negative control, was found to reside on FR-positive tumor masses and significantly reduced tumor growth. In intraperitoneal models, early accumulation on free-floating clumps of ovarian cancer cells and solid peritoneal masses was evident after 1 h, and tumor uptake was stable for up to 3 h. The high tumor uptake determined the efficacy of (131)I AFRA-DFM5.3. The best antitumor activity, with more than 50% of treated animals cured, was achieved with 2 locoregional treatments of intraperitoneally growing tumors on days 2 and 9. CONCLUSION: These results suggest that radioimmunotherapy with (131)I-AFRA-DFM5.3 is feasible and leads to significantly prolonged survival. These preclinical data provide the basis for the rationale design of therapeutic treatments of ovarian cancer patients with a radiolabeled anti-FR antibody fragment. PMID- 22068898 TI - Evaluation of 177Lu-DOTA-sst2 antagonist versus 177Lu-DOTA-sst2 agonist binding in human cancers in vitro. AB - Somatostatin receptor targeting of neuroendocrine tumors using radiolabeled somatostatin agonists is today an established method to image and treat cancer patients. However, in a study using an animal tumor model, somatostatin receptor antagonists were shown to label sst(2)- and sst(3)-expressing tumors in vivo better than agonists, with comparable affinity even though they are not internalized into the tumor cell. In the present study, we evaluated the in vitro binding of the antagonist (177)Lu-DOTA-pNO(2)-Phe-c (DCys-Tyr-DTrp-Lys-Thr-Cys) DTyrNH(2) ((177)Lu-DOTA-BASS) or the (177)Lu-DOTATATE agonist to sst(2) expressing human tumor samples. METHODS: Forty-eight sst(2)-positive human tumor tissue samples (9 ileal carcinoids, 10 pheochromocytomas, 7 breast carcinomas, 10 renal cell carcinomas, and 12 non-Hodgkin lymphomas) were analyzed by in vitro receptor autoradiography for the expression of sst(2), comparing the binding capacity of (177)Lu-DOTA-BASS and (177)Lu-DOTATATE in successive tissue sections. The autoradiograms were quantitated using an electronic autoradiography detection system. RESULTS: In all cases, the radiolabeled antagonist bound to more receptor sites than did the agonist. The mean ratios of the antagonist (177)Lu-DOTA-BASS to the agonist (177)Lu-DOTATATE were 4.2 +/- 0.5 in the 9 ileal carcinoids, 12 +/ 3 in the 10 pheochromocytomas, 11 +/- 4 in the 7 breast carcinomas, 5.1 +/- 0.6 in the 10 renal cell carcinomas, and 4.8 +/- 0.7 in the 12 non-Hodgkin lymphomas. CONCLUSION: The present in vitro human data, together with previous in vivo animal tumor data, are strong arguments indicating that sst(2) antagonists may be worth testing in vivo in patients in a wide range of tumors including nonneuroendocrine tumors. PMID- 22068899 TI - Bio-inspired synthesis: understanding and exploitation of the crystallization process from amorphous precursors. AB - Many biominerals, such as mollusk nacre, sea urchin, bone and teeth, are found to form by an amorphous precursor pathway, and these biominerals have remarkable properties, which are better than their artificial material counterparts that are formed at high temperatures and high pressures. More than ever, synthesizing technologically relevant materials following nature's way with a specific size, shape, orientation, organization, and complex form has been a focus of ongoing interest due to the increasing need for low cost and environmentally friendly approaches to processing advanced materials. Herein, we present recent developments in the crystallization process from amorphous precursors by primarily drawing on results from our own laboratory, and discuss some unique characteristics from the transformation process that can be exploited for the design and synthesis of artificial functional materials. PMID- 22068900 TI - QT/RR Coupling and Gender Differences. AB - Data provided by THEW was used to test QT gender differences. Three QT/RR models were used during analysis: a transfer function model (TRF), a model based on exponential weighting of RR intervals (EXP), and an EXP model with additive direct coupling with RR intervals (EXPDC). Data from 81 men and 73 women was analyzed.Women have a significantly higher QTc (p<10(-6)), steeper Gain(L) (QT/RR slope, gain for slow RR variability, p<0.01), faster tau (QT adaptation, p<0.05), higher Gain(F) (gain for fast RR variability, immediate change of QT, p<0.05) and higher QT random variability (p<0.05).The higher prevalence of arrhythmias in women, given by longer QTc, is compensated to some extent by a higher level of Gain(F) and faster tau. The proarrhythmic influence of drugs may originate in a change of Gain(L), Gain(F) or tau without any change in QTc. PMID- 22068901 TI - Synthesis of Nanoporous Iminodiacetic Acid Sorbents for Binding Transition Metals. AB - Iminodiacetic acid (IDAA) forms strong complexes with a wide variety of metal ions. Using self-assembled monolayers in mesoporous supports (SAMMS) to present the IDAA ligand potentially allows for multiple metal-ligand interactions to enhance the metal binding affinity relative to that of randomly oriented polymer based supports. This manuscript describes the synthesis of a novel nanostructured sorbent material built using self-assembly of a IDAA ligand inside a nanoporous silica, and demonstrates its use for capturing transition metal cations, and anionic metal complexes, such as PdCl(4) (-2). PMID- 22068902 TI - One-pot synthesis of reduced graphene oxide-cadmium sulfide nanocomposite and its photocatalytic hydrogen production. AB - Reduced graphene oxide (RGO)-cadmium sulfide (CdS) nanocomposites were successfully prepared by a one-pot solvothermal process without pretreatment of graphene oxide (GO) and a precipitation process, in which GO needs to be pre reduced by hydrazine. The as-obtained RGO-CdS nanocomposites were used as photocatalysts for hydrogen production under visible light irradiation, and it was found that the product derived from the one-pot solvothermal process showed much better photoactivity than that from the precipitation method. PMID- 22068903 TI - Solid-state photochromism of chromenes: enhanced photocoloration and observation of unstable colored species at low temperatures. AB - Solid-state photochromism of benzopyrans and naphthopyrans (chromenes) was investigated in the temperature range between 300 and 80 K. Variable-temperature diffuse reflectance spectroscopy of microcrystalline powders showed that the extent of photocoloration was greatly enhanced at low temperatures. All the chromenes examined exhibited solid-state photochromism at low temperatures, even when they showed little or no photocoloration at room temperature. The solid state photochromic properties of the chromenes were quite similar to those reported for analogous photochromic compounds of spiropyrans and spirooxazines, which indicates that these classes of compounds are generally photochromic even in the solid state. Photobleaching reactions of the colored merocyanine forms proceeded at low temperatures through the formation of a colorless intermediate, instead of directly resuming the original closed form. In addition to two stable planar merocyanine forms, which are usually observed in the photochromic reactions in solution, photoreactions at low temperatures allowed us to observe unstable colored species, which were tentatively assigned as nonplanar cisoid forms, and were stabilized in the solid state at low temperatures. PMID- 22068906 TI - Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease. AB - Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and 10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival. PMID- 22068907 TI - Protective effect of the APOE-e3 allele in Alzheimer's disease. AB - Although several alleles of susceptibility to Alzheimer's disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitoria, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95%CI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46, 95%CI = 0.30 0.67; P < 0.0001). This study may provide a new insight into the role of the APOE e3 allele in the etiology of AD and might help to establish a profile of risk for AD in the population from Vitoria, ES. PMID- 22068908 TI - Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCgamma1. AB - The mitogenic effects of periodic mechanical stress on chondrocytes have been studied extensively but the mechanisms whereby chondrocytes sense and respond to periodic mechanical stress remain a matter of debate. We explored the signal transduction pathways of chondrocyte proliferation and matrix synthesis under periodic mechanical stress. In particular, we sought to identify the role of the MEK1/2-ERK1/2 signaling pathway in chondrocyte proliferation and matrix synthesis following cyclic physiologic mechanical compression. Under periodic mechanical stress, both rat chondrocyte proliferation and matrix synthesis were significantly increased (P < 0.05) and were associated with increases in the phosphorylation of Src, PLCgamma1, MEK1/2, and ERK1/2 (P < 0.05). Pretreatment with the MEK1/2-ERK1/2 selective inhibitor, PD98059, and shRNA targeted to ERK1/2 reduced periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis (P < 0.05), while the phosphorylation levels of Src-Tyr418 and PLCgamma1-Tyr783 were not inhibited. Proliferation, matrix synthesis and phosphorylation of MEK1/2-Ser217/221 and ERK1/2-Thr202/Tyr204 were inhibited after pretreatment with the PLCgamma1 inhibitor U73122 in chondrocytes in response to periodic mechanical stress (P < 0.05), while the phosphorylation site of Src-Tyr418 was not affected. Inhibition of Src activity with PP2 and shRNA targeted to Src abrogated chondrocyte proliferation and matrix synthesis (P < 0.05) and attenuated PLCgamma1, MEK1/2 and ERK1/2 activation in chondrocytes subjected to periodic mechanical stress (P < 0.05). These findings suggest that periodic mechanical stress promotes chondrocyte proliferation and matrix synthesis in part through the Src-PLCgamma1-MEK1/2-ERK1/2 signaling pathway, which links these three important signaling molecules into a mitogenic cascade. PMID- 22068909 TI - Catalytic enantioselective addition of terminal 1,3-diynes to aromatic ketones: facile access to chiral nonracemic tertiary alcohols. AB - An efficient, catalytic, and enantioselective 1,2-addition of terminal 1,3-diynes to aromatic ketones was realized in the presence of 10 mol% of a Cu(OTf)(2) hydroxycamphor-sulfonamide complex, affording chiral tertiary alcohols in up to 94% yield and 90% ee. PMID- 22068910 TI - Newborn screening for severe combined immunodeficiency; the Wisconsin experience (2008-2011). AB - Severe combined immunodeficiency is a life-threatening primary immune deficiency characterized by low numbers of naive T cells. Early diagnosis and treatment of this disease decreases mortality. In 2008, Wisconsin began newborn screening of infants for severe combined immunodeficiency and other forms of T-cell lymphopenia by the T-cell receptor excision circle assay. In total, 207,696 infants were screened. Seventy-two infants had an abnormal assay. T-cell numbers were normal in 38 infants, abnormal in 33 infants, and not performed in one infant, giving a positive predictive value for T-cell lymphopenia of any cause of 45.83% and a specificity of 99.98%. Five infants with severe combined immunodeficiency/severe T-cell lymphopenia requiring hematopoietic stem cell transplantation or other therapy were detected. In summary, the T-cell receptor excision circle assay is a sensitive and specific test to identify infants with severe combined immunodeficiency and severe T-cell lymphopenia that leads to life saving therapies such as hematopoietic stem cell transplantation prior to the acquisition of severe infections. PMID- 22068911 TI - The influence of interleukin-32gamma on osteoclastogenesis with a focus on fusion related genes. AB - We previously reported that interleukin-32 gamma (IL-32gamma) has a direct effect on osteoclast differentiation and activation in vitro in the context of receptor activator of NF-kappaB ligand (RANKL) co-stimulation. However, the stage of osteoclast differentiation at which IL-32gamma exerts its effect was not determined. Here, we demonstrated that IL-32gamma plays an important role in the fusion of preosteoclasts to yield multinuclear osteoclasts, particularly large osteoclasts. The synergistic effect of IL-32gamma on RANKL-induced formation of multinuclear osteoclasts was readily apparent when cells were treated with IL 32gamma at the fusion stage. In addition, we demonstrated that IL-32gamma induced the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and NFATc1 inactivation by cyclosporine treatment attenuated the effect of IL-32gamma. These results indicate that IL-32gamma is a potential mediator of osteoclast fusion, likely through up-regulation of NFATc1 and DC-STAMP. PMID- 22068912 TI - Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. AB - The FUT2 (Secretor) gene is responsible for the presence of ABO histo-blood group antigens on the gastrointestinal mucosa and in bodily secretions. Individuals lacking a functional copy of FUT2 are known as "nonsecretors" and display an array of differences in susceptibility to infection and disease, including Crohn disease. To determine whether variation in resident microbial communities with respect to FUT2 genotype is a potential factor contributing to susceptibility, we performed 454-based community profiling of the intestinal microbiota in a panel of healthy subjects and Crohn disease patients and determined their genotype for the primary nonsecretor allele in Caucasian populations, W143X (G428A). Consistent with previous studies, we observe significant deviations in the microbial communities of individuals with Crohn disease. Furthermore, the FUT2 genotype explains substantial differences in community composition, diversity, and structure, and we identified several bacterial species displaying disease-by genotype associations. These findings indicate that alterations in resident microbial communities may in part explain the variety of host susceptibilities surrounding nonsecretor status and that FUT2 is an important genetic factor influencing host-microbial diversity. PMID- 22068913 TI - Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance. AB - Although in vitro models have been a cornerstone of anti-cancer drug development, their direct applicability to clinical cancer research has been uncertain. Using a state-of-the-art Taqman-based quantitative RT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of six cancer types, in established cancer cell lines (grown in monolayer, 3D scaffold, or in xenograft) and clinical samples, either containing >75% tumor cells or microdissected. The MDR transcriptome was determined a priori based on an extensive curation of the literature published during the last three decades, which led to the enumeration of 380 genes. No correlation was found between clinical samples and established cancer cell lines. As expected, we found up-regulation of genes that would facilitate survival across all cultured cancer cell lines evaluated. More troubling, however, were data showing that all of the cell lines, grown either in vitro or in vivo, bear more resemblance to each other, regardless of the tissue of origin, than to the clinical samples they are supposed to model. Although cultured cells can be used to study many aspects of cancer biology and response of cells to drugs, this study emphasizes the necessity for new in vitro cancer models and the use of primary tumor models in which gene expression can be manipulated and small molecules tested in a setting that more closely mimics the in vivo cancer microenvironment so as to avoid radical changes in gene expression profiles brought on by extended periods of cell culture. PMID- 22068914 TI - Persisting symptoms after intrathoracic anastomotic leak following oesophagectomy for cancer. AB - BACKGROUND: Intrathoracic anastomotic leak is a major cause of postoperative mortality and morbidity after resection for oesophageal cancer. Little is known about persisting symptoms after this complication. In this Swedish nationwide cohort study, it was hypothesized that intrathoracic anastomotic leak makes patients more susceptible to persisting eating difficulties, odynophagia, dysphagia, trouble swallowing saliva and reflux. METHODS: Patients who underwent oesophagectomy for oesophageal cancer, and had reconstruction with a gastric conduit and an intrathoracic anastomosis, between April 2001 and December 2005 were included. Symptoms were measured using an oesophageal cancer-specific health related quality-of-life questionnaire (QLQ-OES18), developed by the European Organization for Research and Treatment of Cancer. Multivariable logistic regression models were used to calculate risk estimates for symptoms, expressed as odds ratio (OR) with 95 per cent confidence interval, 6 months after intrathoracic anastomotic leakage. RESULTS: Among the 277 patients included in the study, the 29 patients with an intrathoracic anastomotic leak had a fourfold increased risk (OR 4.05, 1.47 to 11.16) of eating difficulties and a more than twofold greater risk (OR 2.59, 1.15 to 5.82) of odynophagia, 6 months after surgery, compared with patients without a leak. There was a twofold increased risk of trouble swallowing, but this was not statistically significant (OR 1.98, 0.58 to 6.67). CONCLUSION: Patients with an intrathoracic anastomotic leak after oesophageal cancer surgery were at increased risk of eating difficulties and odynophagia 6 months after surgery. Higher risks of reflux and dysphagia were not found among patients with anastomotic leak. PMID- 22068915 TI - Crystal structure, electronic properties and cytotoxic activity of palladium chloride complexes with monosubstituted pyridines. AB - Palladium(II) complexes attract great attention due to their remarkable catalytic and biological activity. In the present study X-ray characterization, UV-Vis and Time-Dependent Density Functional Theory (TD-DFT) calculations for six PdCl(2)(XPy)(2) complexes (where: Py = pyridine; X = H, CH(3) or Cl) were applied in order to investigate substituent effects on their crystal structures and electronic properties and to combine the results with their catalytic and cytotoxic activity. The structures of complexes PdCl(2)(3-MePy)(2), PdCl(2)(4 MePy)(2) and PdCl(2)(2-ClPy)(2), have been described for the first time and we compared our results with available data for the whole series of six complexes. All compounds exhibit a square planar coordination geometry in which the palladium ion coordinates two nitrogen atoms of pyridine ligands and two chlorine atoms in trans positions. For complexes with ortho substituted XPy ligands a cis disposition of substituents takes place, whereas for other ligands: 3-MePy and 3 ClPy--the substituents are in trans positions. For XPy the energies of pi-pi* and n-pi* transitions depend on the position and nature of the X substituent in the XPy ring. After complex formation a hipsochromic shift (24-34 nm) of pi-pi* and a bathochromic shift of n-pi* bands are observed. The UV-Vis spectra of PdCl(2)(XPy)(2) confirm that square planar coordination geometry of complexes I VI and two dpi-pi* transitions are expected. With the help of the TD-DFT calculations we proved that dpi-pi* transitions in solutions of PdCl(2)(XPy)(2) complexes result from MLCT (metal-to-ligand charge transfer) with contribution from chlorine atoms to palladium. We also studied substituent effects on cytotoxic properties of Pd(II) complexes against the human breast cancer cell line MCF7, the human prostate cancer cell line PC3, and the human T-cell lymphoblast-like cell line CCRF. The studied complexes were the most active against the CCRF cell line and less or even no cytotoxic effect was observed for PC3 cells. Complexes with MePy ligands showed increased cytotoxic activity compared to unsubstituted pyridine ligands. PMID- 22068916 TI - Radiofrequency heating induced by 7T head MRI: thermal assessment using discrete vasculature or Pennes' bioheat equation. AB - PURPOSE: To evaluate and compare the maximum temperature (T(max) ) in the head after exposure to a 300 MHz radiofrequency (RF) field induced by a magnetic resonance imaging (MRI) coil using two thermal simulation methods: Pennes' bioheat equation (PBHE) and discrete vasculature (DIVA). MATERIALS AND METHODS: The electromagnetic field induced in the head by a 7T birdcage coil was simulated using finite-difference time-domain (FDTD) and validated by MRI. The specific absorption rate (SAR) distributions normalized to the 10-gram maximum or the whole-head average were used for PBHE and DIVA simulations. RESULTS: For all cases, the T(max) in PBHE was slightly higher than in DIVA. The T(max) was 37.9 38.4 degrees C, depending on the simulation method or perfusion rate. CONCLUSION: In some situations, RF exposure limited to SAR(max,10g) led to a T(max) higher than allowed by International Electrotechnical Commission (IEC) regulations. Therefore, it is advisable to use thermal simulations to evaluate RF safety of MRI. The simulation method used only slightly influenced the observed maximum temperature; the observed temperature with PBHE was higher in all situations. So PBHE is an appropriate method for RF safety assessment of MRI in the head. Using DIVA simulations, it was found unlikely that the body temperature increases significantly due to energy deposited by a head coil under normal circumstances. PMID- 22068917 TI - Preventive oral supplementation with glutamine and arginine has beneficial effects on the intestinal mucosa and inflammatory cytokines in endotoxemic rats. AB - The objective of this study was to evaluate the effect of oral supplementation with a combination of arginine and glutamine on the intestinal mucosa and inflammatory cytokines of lipopolysaccharide (LPS)-induced adult rats. Fifty Sprague-Dawley rats (average weight of 185 +/- 15 g) were randomly divided into five groups: control group A (CA) and control group B (CB), both orally supplemented with 0.9% saline; group Arg, supplemented with 300 mg/kg day(-1) arginine; group Gln, supplemented with 300 mg/kg day(-1) glutamine; group AG, supplemented with 150 mg/kg day(-1) arginine and 150 mg/kg day(-1) glutamine. The experiment lasted for 2 weeks. Food intake and body weight were measured during the experiment. At 10.00 h of day 15, animals were injected with 4 mg/kg LPS (group CB, Arg, Gln, and AG) or sterile saline (group CA) after supplementation. Then at 14.00 h, all animals were killed and blood and tissue collected. The results showed that compared with group CB, arginine concentration tended to be increased (P > 0.05) in group Arg and AG, while there was no significant difference in glutamine concentration among the groups challenged with LPS. Oral supplementation with arginine or/and glutamine mitigated morphology impairment (lower villus height, P < 0.05) in the jejunum and ileum induced by LPS challenge. LPS administration resulted in a significant increase in TNF-alpha, IL 1beta, IL-6 and IL-10 mRNA abundance. Arginine only significantly decreased TNF alpha mRNA abundance in the ileum, while glutamine significantly decreased both TNF-alpha and IL-10 mRNA in the ileum. A combination of arginine and glutamine significantly decreased TNF-alpha and IL-1beta mRNA abundance in both the jejunum and ileum, while they also significantly decreased anti-inflammatory IL-10 in the ileum. These results revealed that an oral supply of combined arginine and glutamine had more favorable effects on the intestinal mucosa and inflammatory cytokines than a supply of arginine or glutamine alone. PMID- 22068918 TI - The high fermentative metabolism of Kluyveromyces marxianus UFV-3 relies on the increased expression of key lactose metabolic enzymes. AB - The aim of this work was to obtain insights about the factors that determine the lactose fermentative metabolism of Kluyveromyces marxianus UFV-3. K. marxianus UFV-3 and Kluyveromyces lactis JA6 were cultured in a minimal medium containing different lactose concentrations (ranging from 0.25 to 64 mmol l(-1)) under aerobic and hypoxic conditions to evaluate their growth kinetics, gene expression and enzymatic activity. The increase in lactose concentration and the decrease in oxygen level favoured ethanol yield for both yeasts but in K. marxianus UFV-3 the effect was more pronounced. Under hypoxic conditions, the activities of beta galactosidase and pyruvate decarboxylase from K. marxianus UFV-3 were significantly higher than those in K. lactis JA6. The expression of the LAC4 (beta-galactosidase), RAG6 (pyruvate decarboxylase), GAL7 (galactose-1-phosphate uridylyltransferase) and GAL10 (epimerase) genes in K. marxianus UFV-3 was higher under hypoxic conditions than under aerobic conditions. The high expression of genes of the Leloir pathway, LAC4 and RAG6, associated with the high activity of beta-galactosidase and pyruvate decarboxylase contribute to the high fermentative flux in K. marxianus UFV-3. These data on the fermentative metabolism of K. marxianus UFV-3 will be useful for optimising the conversion of cheese whey lactose to ethanol. PMID- 22068919 TI - The Toxicology Investigators Consortium Case Registry-the 2010 experience. AB - INTRODUCTION: The American College of Medical Toxicology Case Registry was established in 2010 as a method of identifying cases cared for by medical toxicologists at participating institutions. The Registry allows for the extraction of information from medical records making it the most robust multicenter database on chemical toxicities in existence. The current report is a summary of the data collected in 2010. METHODS: All cases seen by medical toxicologists at participating institutions were entered on a database. Information characterizing patients entered in 2010 was tabulated. RESULTS: Over the course of 2010, the number of institutions contributing cases grew from 4 to 50. Three thousand nine hundred forty-eight cases were entered. Emergency departments were the most common source of consultations, accounting for approximately 50% of the cases. The most common reason for consultations was for pharmaceutical overdoses, which occurred in 42% of the patients. The most common classes of agents were non-opioid analgesics (14%), sedative/hypnotics/muscle relaxants (10%), ethanol (8%), and opioids (8%). N-acetylcysteine was the most common antidote used, followed by opioid antagonists, sodium bicarbonate, and physostigmine. Anti-crotalidae Fab fragments were administered in 72% of the cases in which an antivenin was used. Signals were detected suggesting the possibility that amlodipine and metoprolol were associated with greater toxicity than had been previously recognized. CONCLUSIONS: The Registry can identify and characterize patients who have sufficient toxicity to require a consultation by a medical toxicologist. Hypotheses for further investigation emerged from the data. The Registry appears to be a potentially powerful tool for toxicovigilance and research. PMID- 22068920 TI - Increased rates of asthma among World Trade Center disaster responders. AB - BACKGROUND: Studies have documented high rates of asthma symptoms among responders to the World Trade Center (WTC) disaster. However, whether there are increased rates of asthma among responders compared to the general population is unknown. METHODS: The study population consisted of a prospective cohort of 20,834 responders participating in the WTC Medical Monitoring and Treatment Program between July 2002 and December 2007. We calculated prevalence and standardized morbidity ratios (SMRs) of lifetime asthma and 12-month asthma (defined as >=1 attacks in the prior 12 months) among WTC responders. The comparison population consisted of >200,000 adults who completed the National Health Interview Survey in 2000 (for pre-9/11 comparisons) and between 2002 and 2007 (for post-9/11 comparisons). RESULTS: WTC responders were on average 43 +/- 9 years old, 86% male, 59% white, and 42% had an occupation in protective services. The lifetime prevalence of asthma in the general population was relatively constant at about 10% from 2000 to 2007. However, among WTC responders, lifetime prevalence increased from 3% in 2000, to 13% in 2002, and 19% in 2007. The age-adjusted overall SMR for lifetime asthma among WTC responders was 1.8 (95% CI: 1.8-1.9) for men and 2.0 (95% CI: 1.9-2.1) for women. Twelve-month asthma was also more frequent among WTC responders compared to the general population (SMR 2.4, 95% CI: 2.2-2.5) for men and 2.2 (95% CI: 2.0-2.5) for women. CONCLUSIONS: WTC responders are at an increased risk of asthma as measured by lifetime prevalence or active disease. PMID- 22068922 TI - Rivastigmine transdermal patch and capsule in Alzheimer's disease: influence of disease stage on response to therapy. AB - OBJECTIVES: The cholinesterase inhibitor rivastigmine is approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). This exploratory, hypothesis-forming analysis assessed response to rivastigmine according to severity of dementia at baseline. METHODS: This was a retrospective analysis of a large randomized, placebo-controlled trial (ENA713D2320). AD patients treated with 9.5 mg/24 h rivastigmine patch, 17.4 mg/24 h rivastigmine patch, rivastigmine capsule (12 mg/day), or placebo were stratified according to baseline Mini-Mental State Examination (MMSE) scores: >=7 to <=12 (severe disease), >=13 to <=15 (moderately severe), >=16 to <=18 (moderate), or >=19 to <=25 (mild to moderate). Changes from baseline at Week 24 on Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) were assessed. RESULTS: Based on baseline MMSE scores, 141, 228, 333, and 348 patients had severe, moderately severe, moderate, and mild to moderate dementia. Worsening of ADAS cog, ADCS-CGIC, and ADCS-ADL scores in patients receiving placebo were greater in patients with more severe dementia. Significant improvements versus placebo were seen with rivastigmine patch and/or capsule on ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients with severe, moderately severe, and moderate AD (all p < 0.05). However, no significant improvements were seen in rivastigmine-treated patients with mild to moderate AD. CONCLUSIONS: Rivastigmine benefits AD patients across dementia stages. Similar to previous cholinesterase inhibitor studies, greatest treatment effects with rivastigmine patch and capsule were seen in patients with more advanced dementia, most likely driven by greater placebo decline in this population. PMID- 22068923 TI - Depression and its correlates in older adults in Ukraine. AB - OBJECTIVE: Little is known about the epidemiology of late life depression in Eastern Europe. This study examined the 12-month prevalence and correlates of DSM IV major depressive episode (MDE) in adults age 50 years and over in Ukraine. The correlates included demographic factors, mental health and alcohol history, physical conditions, and impairments in functioning. METHODS: A cross-sectional survey was conducted in Ukraine using the Composite International Diagnostic Interview (CIDI-3.0) as part of the World Health Organization-World Mental Health Survey Initiative. The sample included 1843 respondents age 50-91. Unadjusted and adjusted odds ratios were used to examine associations of the risk factors with 12-month MDE in men and women separately. RESULTS: The 12-month prevalence of MDE was 14.4% in women and 7.1% in men. In both sexes, history of MDE before age 50 and poor self-assessed mental/physical health were significantly associated with MDE. Additionally, in men, living alone, 5+ physician visits, and role impairment, but not alcoholism, were associated with depression; in women, poverty, history of anxiety disorder, medical conditions, and cognitive and self care impairment were significant. CONCLUSIONS: The 12-month prevalence of late life MDE was substantially higher in Ukraine than in Western Europe and other developed countries. The risk factors, however, were similar to those found outside Ukraine. Depression is a recurrent condition, and history of depression was the strongest risk factor. Overall, the results show that older people in Ukraine constitute a high-risk group for MDE and would therefore benefit from targeted interventions by primary care physicians. PMID- 22068924 TI - What did you expect? PMID- 22068921 TI - MEG-SIM: a web portal for testing MEG analysis methods using realistic simulated and empirical data. AB - MEG and EEG measure electrophysiological activity in the brain with exquisite temporal resolution. Because of this unique strength relative to noninvasive hemodynamic-based measures (fMRI, PET), the complementary nature of hemodynamic and electrophysiological techniques is becoming more widely recognized (e.g., Human Connectome Project). However, the available analysis methods for solving the inverse problem for MEG and EEG have not been compared and standardized to the extent that they have for fMRI/PET. A number of factors, including the non uniqueness of the solution to the inverse problem for MEG/EEG, have led to multiple analysis techniques which have not been tested on consistent datasets, making direct comparisons of techniques challenging (or impossible). Since each of the methods is known to have their own set of strengths and weaknesses, it would be beneficial to quantify them. Toward this end, we are announcing the establishment of a website containing an extensive series of realistic simulated data for testing purposes ( http://cobre.mrn.org/megsim/ ). Here, we present: 1) a brief overview of the basic types of inverse procedures; 2) the rationale and description of the testbed created; and 3) cases emphasizing functional connectivity (e.g., oscillatory activity) suitable for a wide assortment of analyses including independent component analysis (ICA), Granger Causality/Directed transfer function, and single-trial analysis. PMID- 22068925 TI - Very large magnetoresistive graphene disk with negative permittivity. AB - At room temperature a large magnetoresistance (MR) of up to 70% is observed in graphene. Both graphene size and surface functionality influence the MR behavior significantly. The conductivity increases linearly with increasing temperature and a unique negative permittivity over a wide frequency range from 10(3) to 10(6) Hz is observed at room temperature. PMID- 22068926 TI - Regulation of CYP24 splicing by 1,25-dihydroxyvitamin D3 in human colon cancer cells. AB - CYP24 is a well-established vitamin D receptor (VDR) target gene. The active VDR ligand 1,25(OH)2D3 regulates its own catabolism by increasing CYP24 expression. It is well known that in the presence of 1,25(OH)2D3, VDR binds to VDREs in the promoter region of CYP24 and initiates CYP24 transcription. However, little is known about the role of 1,25(OH)2D3 in the posttranscriptional modulation of CYP24. In this study, we investigated the functional significance of 1,25(OH)2D3 in CYP24 RNA splicing in colon cancer cells. Using RT-PCR, we found that 1,25(OH)2D3 actively induces CYP24 splicing in a time-dependent manner and CYP24 splicing pattern could be cell type or tissue specific. The induction of RNA splicing by 1,25(OH)2D3 was mainly CYP24 selective. Treatment of cells with parathyroid hormone inhibited basal CYP24 splicing, but failed to inhibit 1,25(OH)2D3-induced CYP24 splicing. Further experiments demonstrated that new RNA synthesis was required for the induction of CYP24 splicing by vitamin D. In addition, alteration of multiple signaling pathways also affected CYP24 splicing and cellular sensitivity in response to vitamin D appeared to correlate with the induction of CYP24 splicing. These results suggest that 1,25(OH)2D3 not only regulates CYP24 transcription, but also plays an important role in posttranscriptional modulation of CYP24 by inducing its splicing. Our findings reveal an additional regulatory step that makes the vitamin D mediated action more prompt and efficient. PMID- 22068927 TI - Estrogen receptor (ER) expression and function in the pregnant human myometrium: estradiol via ERalpha activates ERK1/2 signaling in term myometrium. AB - Estrogens are thought to promote labor by increasing the expression of pro contraction genes in myometrial cells. The specific estrogen receptors ((ERs: ERalpha and ERbeta (also known as ESR1 and ESR2)) and G protein-coupled receptor 30 (GPR30; also known as G protein-coupled estrogen receptor 1)) and signaling pathways that mediate these actions are not clearly understood. In this study, we identified the ERs expressed in the pregnant human myometrium and determined a key extranuclear signaling pathway through which estradiol (E(2)) modulates expression of the gene encoding the oxytocin receptor (OXTR), a major pro contraction protein. Using quantitative RT-PCR, we found that ERalpha and GPR30 mRNAs were expressed in the human pregnant myometrium while ERbeta mRNA was virtually undetectable. While mRNA encoding ERalpha was the predominant ER transcript in the pregnant myometrium, ERalpha protein was largely undetectable in myometrial tissue by immunoblotting. Pharmacological inhibition of 26S proteasome activity increased ERalpha protein abundance to detectable levels in term myometrial explants, however, indicating rapid turnover of ERalpha protein by proteasomal processing in the pregnant myometrium. E(2) stimulated rapid extranuclear signaling in myometrial explants, as evidenced by increased extracellularly regulated kinase (ERK1/2) phosphorylation within 10 min. This effect was inhibited by pre-treatment with an ER antagonist, ICI 182 780, indicating the involvement of ERalpha. Inhibition of ERK signaling abrogated the ability of E(2) to stimulate OXTR gene expression in myometrial explants. We conclude that estrogenic actions in the human myometrium during pregnancy, including the stimulation of contraction-associated gene expression, can be mediated by extranuclear signaling through ERalpha via activation of the ERK/mitogen-activated protein kinase pathway. PMID- 22068928 TI - Mechanism of benzene hydroxylation by high-valent bare Fe(IV)=O2+: explicit electronic structure analysis. AB - The conversion of benzene to phenol by high-valent bare FeO(2+) was comprehensively explored using a density functional theory method. The conductor like screen model (COSMO) was used to mimic the role of solvent effect with acetonitrile chosen as the solvent. Two radical mechanisms and one oxygen insertion mechanism were tested for this conversion. The first radical mechanism can also be named as the concerted mechanism in which the hydrogen-atom abstraction process is accomplished via a four-centered transition state. The second radical mechanism is initiated by a direct hydrogen-atom abstraction with a collinear C-H-O transition structure. It is actually the same as the well accepted rebound mechanism for the C-H bond activation by heme and nonheme iron oxo catalysts. The third is an oxygen insertion mechanism which is essentially an aromatic electrophilic attack leading to an arenium sigma-complex intermediate. The formation of a precomplex with an eta(4) coordinate environment in the first radical mechanism is energetically more favorable. However, the relatively lower activation energy barrier of the oxygen insertion mechanism compared to the radical ones makes it highly competitive if the Fe=O(2+) collides with benzene in the proper orientation. The detailed potential energy surfaces also indicate that the second radical mechanism, i.e., the benzene C-H bond activation through the rebound mechanism, is less favorable. This thorough theoretical study, especially the electronic structure analysis, may offer very important clues for understanding and studying C-H bond activation by iron-based catalysts and enzymatic reactions in protein active pockets. PMID- 22068930 TI - Sports therapy for attention, cognitions and sociality. AB - The aim of the present study was to understand if sport improves attention symptoms, social competency, and cognitive functions in children with attention deficit and hyperactivity disorder (ADHD). The present study was designed as a 6 week, prospective trial, including 12 sessions of education/sports therapy. 13 ADHD children participated in a 90-min athletic activity (sports-cADHD) twice a week, while 15 ADHD children received education on behavior control (edu-cADHD). During the 6-week treatment period, the sports-cADHD group showed greater improvements in DuPaul's ADHD Rating Scale scores, parent and teacher version (K ARS-PT), compared to those of the edu-sADHD group. The cognitive functions assessed with the digit symbol and Trail-Making Test part B (TMT B) were improved in the sports-cADHD group, while the cognitive functions observed in the edu sADHD group were not significantly changed. The cooperativeness scores in the sports-cADHD group were greatly increased compared to those of the edu-sADHD group. The results demonstrated a positive correlation with sports and improvement in attention symptoms, cognitive symptoms and social skills. The results of the present study suggest that therapy in the form of athletic activity may increase social competency in children with ADHD, as demonstrated by improved cognitive functions. PMID- 22068931 TI - Muscle protein turnover in endurance training: a review. AB - There has been much debate about skeletal muscle capacity to adapt to long lasting endurance exercise. Exercise in the aerobic zone of metabolism does not result in hypertrophy of skeletal muscle fibres but increases their oxidative capacity. The duration and intensity of an exercise session determines the time period of depressed muscle protein synthesis and increased degradation rate during the recovery period after exercise. Protein turnover characterizes the renewal processes of muscle proteins and the functional capacity of muscle. The turnover rate of myofibrillar proteins is slow in comparison with mitochondrial proteins and depends on the oxidative capacity of muscle fibres. The turnover rate of myofibrillar proteins in the same muscle is different and is also different within the myosin molecule between myosin heavy and light chain isoforms. The turnover rate of muscle proteins in endurance training shows the adaptation of skeletal muscle to long-lasting exercise via remodelling of muscle structures. Adaptational coordination between myofibrillar and mitochondrial compartments shows the physiological role and adaptational capacity of skeletal muscle to endurance training. It is challenging to use muscle protein turnover for the purposes of monitoring the training process of endurance athletes, optimizing training programs and preventing overtraining. PMID- 22068929 TI - Cytokines and sudden infant death. AB - BACKGROUND: It has been hypothesised that inflammatory reactions could play an important role in the pathway(s) leading to sudden and unexpected death in infancy. On a molecular level, these reactions are regulated by various cytokines. METHODS: To characterise the role of IL-1beta, IL-6 and TNFalpha more precisely, the concentrations of these cytokines were determined quantitatively using specific ELISA techniques in serum and cerebrospinal fluid (CSF) in 119 cases of sudden infant death. The infants were grouped into four categories (SIDS, SIDS with infection, natural death due to infection and unnatural death). RESULTS: A good correlation was found between CSF and serum for IL-6 (Spearman correlation coefficients (SCC), 0.73) and also for TNFalpha (SCC, 0.57), although the CSF concentrations were lower than that from the serum. There were no significant differences between the categories of death for any of the serum or CSF cytokines. Compared with normal values, increased serum concentrations of IL 1beta, IL-6 and TNFalpha were found in 70%, 69% and 38% of the cases respectively, indicating possible agonal or post-mortem changes of cytokine concentrations. In three cases very high cytokine concentrations were found (mainly for IL-6). This may have contributed to the mechanism of death (cytokine storm) in two of the cases. CONCLUSIONS: In a small group of patients, very high cytokine concentrations are a possible explanation for the cause of death ("cytokine storm"). PMID- 22068932 TI - The importance of considering both racial and socioeconomic disparities: A response to Collins and Alpert. PMID- 22068933 TI - Stitching phospholanes together piece by piece: new modular di- and tridentate stereodirecting ligands. AB - The modular one-pot synthesis of a large family of bi- and tridentate 2,5 dimethyl- and 2,5-diphenyl-substituted phospholanes employs air-stable chiral phospholanium chloride salts and primary amines or NH(4)Cl as starting materials. These were transformed into the C(2)-symmetric dimethyl- and diphenylphospholane ligands, which reacted with [Rh(cod)(2)]BF(4) (cod=1,5-cyclooctadiene) to yield the rhodium complexes [Rh(L)(cod)]BF(4) (L=bisphospholane ligands). The corresponding trisphospholane complexes, 11 and 12, were obtained in high yields (81 and 92%, respectively), and fully characterised by NMR spectroscopy, mass spectrometry and elemental analysis. Whilst in the C(3)-symmetric complex 11, containing the tridentate 2,5-dimethylphospholane, the ligand is bound symmetrically, different coordination behaviour was found for the diphenyl substituted complex 12, in which the coordination of only two of the three phospholane moieties to the metal centre was observed. A DFT study at the B3PW91 level established minimum energy structures consistent with experimental findings in solution and in the solid state. The non-coordinated phospholane unit present in 12 allowed further modification of the complex through the coordination of Au(I)-X (X=Cl, C(6)F(5) and tris(trifluoromethyl)phenyl ((F)Mes)) fragments to the pendant phosphane. To investigate the potential of the new ligands, the enantioselective hydrogenation of a series of prochiral olefins as benchmark substrates, using isolated Rh complexes as catalysts, was studied. The substrates included methyl esters of three dehydro-alpha-acetamido acids and two itaconic acid derivatives. In general good to excellent enantioselectivities (of up to >99% ee) were observed. Ligand backbone modification by coordination of bulky Au X substituents to the free phospholane unit in complex 12 led to an outstanding enhancement of the catalyst performance and there was a clear correlation between the properties of the complex periphery and the enantioselectivity. PMID- 22068934 TI - Comparison of three T-Wave Delineation Algorithms based on Wavelet Filterbank, Correlation and PCA. AB - There is a large interest in analysing the QT-interval, as a prolonged QT interval can cause the development of ventricular tachyarrhythmias such as Torsade de Pointes. One major part of QT-analysis is T-end detection. Three automatic T-end delineation methods based on wavelet filterbanks (WAM), correlation (CORM) and Principal Component Analysis PCA (PCAM) have been developed and applied to Physionet QT database.All algorithms tested on Physionet QT database showed good results, while PCAM produced better results than WAM and CORM achieved best results. Standard deviation in sampling points (f(s)=250Hz) have been 33.3 (WAM), 8.0 (PTDM) and 7.8 (CORM). It could be shown that WAM is prone to interference while CORM is the most stable method even under bad conditions. Furthermore it was possible to detect significant QT-prolongation caused by Moxifloxacin in Thorough QT Study # 2 using CORM. QT-prolongation is significantly correlated to blood plasma concentration of Moxifloxacin. PMID- 22068936 TI - Allee effect in exotic and introduced blowflies. AB - We combined two models to investigate the theoretical dynamics of five exotic and native blowfly species in response to the Allee effect by using demographic parameters estimated from experimental populations. Most of the results suggest stabilization of dynamic behavior in response to the Allee effect. However, the results depended on the magnitude of the demographic parameters of each species, and also indicated chaotic fluctuations and limit cycles. The results are discussed in the context of larval aggregation, an important biological process for blowflies, which naturally incorporates the Allee effect. PMID- 22068935 TI - [Dermatobia hominis infection in a 3-year-old child]. AB - In the context of increasing travel to the tropics, outpatient services are more frequently confronted with non-domestic diseases in Europe. A 3-year old child presented with a painful tumor of the scalp. After incision of the furuncle-like lesion, we extracted a larva of the botfly Dermatobia hominis. Botflies are mainly encountered in Central and South America; they should be considered if patients demonstrate a furuncle-like lesion and have returned from a holiday in these endemic regions. PMID- 22068937 TI - Diapause initiation and alterations in the life cycle of Grapholita molesta (Busck) (Lepidoptera: Tortricidae) as induced by photoperiodic conditions. AB - Grapholita molesta (Busck) is one of the major pests of Rosaceae, causing significant damage to buds and fruits. In Southern Brazil, its population density is reduced during Rosaceae dormancy months. The present study evaluated the influence of different photoperiods (L:D) (10:14, 11:13, 12:12, 13:11, 14:10 and 16:8) at 25 +/- 1oC and 60 +/- 10% RH on diapause induction of G. molesta eggs, larvae, prepupae, and pupae. The effects of the photoperiod on the life cycle of non-diapausing insects and on the second generation were also assessed. Prepupal diapause was observed only when eggs and neonates (<= 12h-old larvae) were exposed to photophases from 10h to 14h long. Development of non-diapausing individuals and those from the second generation tended to be longer in photophases between 10h and 14h long. PMID- 22068938 TI - Development and survival of the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae) as a function of temperature: effect on the number of generations in tropical and subtropical regions. AB - The diamondback moth, Plutella xylostella (L.), is the most important pest of brassicaceous crops worldwide. Since temperature is the major abiotic factor influencing insect development and thermal requirements may vary among insect populations, it is important to know the effect of temperature on development and survival of a subtropical strain of P. xylostella. Development and survival of the diamondback moth was evaluated under seven constant temperatures ranging from 10 degrees C to 35 degrees C. Development was completed between 10 degrees C and 32.5 degrees C, but at 35 degrees C all individuals died in the larval stage. Data were fitted to one linear and five nonlinear models. Considering as criteria the goodness of fit and the ability to estimate parameters of biological significance, the models Briere-1 and Briere-2 were the most adequate to describe the relationship between temperature and development of P. xylostella. The linear model demonstrated that P. xylostella required 312.5 degree-days above a lower threshold of 6.3 degrees C to complete development. The degree-day model showed that the number of diamondback moth generations in the tropical region of Brazil is nearly twice the number in the subtropical region of the country. This result explains, at least in part, the higher population levels of this species in the tropical region of Brazil, and also demonstrates that P. xylostella is tolerant to a wide range of temperatures (6.1-32.5 degrees C). Therefore, temperature cannot be considered a limiting factor for the occurrence of diamondback moth throughout the year in most regions of Brazil. PMID- 22068939 TI - Do leaf-litter attributes affect the richness of leaf-litter ants? AB - The search for factors shaping leaf-litter ant communities has received particular attention due to the essential role of these insects in many ecological processes. Here, we aimed to investigate how the number of leaves and leaf morphotypes affect the litter-ant species density at forest edge and interior in an Atlantic Forest remnant in the state of Alagoas, Brazil. This study was developed based on 28 litter plots (1m2 each), 14 in the forest interior and 14 in the forest edge. As we early expected, ant species density increased with increasing both the number of leaves and the number of leaf morphotypes, but this result was clearly influenced by plot location. Contrasting with the forest interior, ant species density did not increase as the number of leaves increased in the forest edge. Possibly, factors such as plant species richness, vegetation structure and environmental conditions affect ant species density as well as promote a patchy distribution of species in ant communities along the edge-to-interior gradient. Our findings suggest that edge-affected forests present more simplified ant communities, with different factors shaping its structure. We encourage future studies to include leaf litter heterogeneity as one of the explanatory variables investigated. PMID- 22068940 TI - Long-term male aggregations of Euglossa melanotricha Moure (Hymenoptera: Apidae) on fern fronds Serpocaulon triseriale (Pteridophyta: Polypodiaceae). AB - A communal dormitory of male orchid bees, Euglossa melanotricha Moure, was monitored over a one-year period, when they passed the night in the fronds of a Serpocaulon triseriale (Polypodiaceae) fern. The bees used the same fronds continuously, moving to neighboring fronds as senescence set in. As many as 49 males were observed together on any one night, clinging to the midribs on the abaxial surface of up to five fern blades with their mandibles. A number of males returned to the same site to pass the night continuously over a number of months, and were observed making physical contact with one another without provoking agonistic behavior. Males of E. melanotricha appeared to prefer sleeping at sites close to nests and potential sources of odoriferous essences, such as orchids (Orchidaceae). PMID- 22068941 TI - Molecules, wing pattern and distribution: an approach to species delimitation in the "loxurina group" (Lepidoptera: Lycaenidae: Penaincisalia). AB - The wide range of morphological variations in the "loxurina group" makes taxa identification difficult, and despite several reviews, serious taxonomical confusion remains. We make use of DNA data in conjunction with morphological appearance and available information on species distribution to delimit the boundaries of the "loxurina" group species previously established based on morphology. A fragment of 635 base pairs within the mtDNA gene cytochrome oxidase I (COI) was analysed for seven species of the "loxurina group". Phylogenetic relationships among the included taxa were inferred using maximum parsimony and maximum likelihood methods. Penaincisalia sigsiga (Balint et al), P. cillutincarae (Draudt), P. atymna (Hewitson) and P. loxurina (C. Felder & R. Felder) were easily delimited as the morphological, geographic and molecular data were congruent. Penaincisalia ludovica (Balint & Wojtusiak) and P. loxurina astillero (Johnson) represent the same entity and constitute a sub-species of P. loxurina. However, incongruence among morphological, genetic, and geographic data is shown in P. chachapoya (Balint & Wojtusiak) and P. tegulina (Balint et al). Our results highlight that an integrative approach is needed to clarify the taxonomy of these neotropical taxa, but more genetic and geographical studies are still required. PMID- 22068942 TI - Barbadocladius Cranston & Krosch, a new genus of Orthocladiinae (Diptera: Chironomidae) from South America. AB - Barbadocladius n. gen. is erected and described in larval, pupal and adult stages for two species: B. andinus sp. nov. and B. limay sp. nov., from Andean streams. The larva is distinctive by virtue of the very large ventromental 'beard' and the anterior parapods with a 'sleeve' of hooklets in addition to apical pectinate claws. The pupa has hooklets on some tergal and sternal intersegmental membranes. The adult, reported only in teneral specimens has hairy eyes, no antennal apical strong seta, no acrostichals, bare and unmarked wings, cylindrical 4th tarsomere subequal in length to the 5th, pulvilli about half the claw length, and hypopygium with anal point, lacking a virga. Molecular phylogenetic analysis eliminates relationships directly to the Eukiefferiella complex (which also have pupal hooklets), or to the Cricotopus group (adults also with hairy eyes), suggesting instead a sister group relationship to a suite of predominantly austral genera of Orthocladiinae. PMID- 22068943 TI - New mariner elements in Anastrepha species (Diptera: Tephritidae). AB - Mariner-like elements (MLE) are members from class II of transposable elements also known as DNA transposons. These elements have a wide distribution among different groups of organisms, including insects, which can be explained by horizontal and vertical gene-transfer. MLE families have been described in tephritid flies and other genera. During screening for Wolbachia bacteria in fruit flies of the genus Anastrepha, we discovered two sequences related to mariner-like elements. Based on these sequences, we designed primers that allowed us to isolate and characterize two new mariner-like elements (Anmar1 and Anmar2) in Anastrepha flies. These elements, which belong to the mellifera and rosa subfamilies have a low nucleotide diversity, and are probably inactive and acquired by vertical transfer. This is the first report of mariner-like transposons in flies found in South America. PMID- 22068944 TI - A new species group of the genus Epicauta Dejean of southern South America, the bella group (Coleoptera: Meloidae). AB - Epicauta includes two subgenera, and within the nominotypical subgenus several species groups. Analyzing species of southern South America, a set of species of Epicauta has the particularity to present two distinctive characters which separates this group from the other species groups of American Epicauta: color pattern of pubescence in elytra is not coincident with color pattern of tegument and endophalic hook robust. Based on these characters I propose a new group of species herein named bella group. This group includes the Neotropical species Epicauta bella Maklin, E. brunneipennis (Haag-Rutemberg), E. diagramma (Burmeister), E. griseonigra (Fairmaire), E. luctifera (Fairmaire), E. riojana (Fairmaire) (new status), and E. zebra (Dohrn). This group is endemic of southern South America, inhabiting the Chaco biogeographical subregion, mainly in the arid northern areas of Argentina. Here we redefine the species of the bella group, consider new characters, illustrate the species in the group, provide maps of their distribution, and a key to identify them. PMID- 22068945 TI - A morphometric and molecular study of Anastrepha pickeli Lima (Diptera: Tephritidae). AB - This study investigated the level of morphometric and genetic variability among populations of Anastrepha pickeli Lima from several localities in Brazil, one locality in Bolivia and one in Paraguay. Traditional and geometric morphometric analyses were used, as well as sequencing of a fragment of the cytochrome oxidase gene (COI). Six variables were measured from the aculeus for traditional morphometric analysis and 14 landmarks from the right wing were used for geometric analysis, using 10 specimes/population. The aculeus tip length, aculeus width at the end of the cloaca opening, and the serrate part length contributed with 62.7% for grouping. According to the results from traditional morphometry, there was no significant difference, but the multivariate tests showed that the canonical variables were statistically significant, indicating a difference in the wing conformation among populations. Molecular phylogenetic analysis indicated that the populations clustered into three clades and revealed a high level of genetic variation within A. pickeli populations from various geographic regions. Anastrepha pickeli populations differed among them according to the methods used in this study, showing incongruence among the methods used. PMID- 22068946 TI - Riethia manauara n. sp., an Amazonian Chironomid (Diptera: Chironomidae) from Brazil. AB - One new species of Riethia Kieffer, Riethia manauara n. sp., is described and figured as male, pupa and larva. The generic diagnosis for pupae and larvae are emended. The specimens were collected from water systems in the Amazon Rainforest in northern Brazil. PMID- 22068947 TI - Plasmid patterns of efficient and inefficient strains of Bacillus thuringiensis against Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae). AB - Bacillus thuringiensis harbors genes encoding Cry proteins found in chromosomes or plasmids of different sizes (4-150 Mb). Although the smaller plasmids are more abundant in B. thuringiensis, their specific function is unknown. As for the megaplasmids, their main recognized function is to harbor cry genes, although the sequencing of some of these plasmids indicates the occurrence of other important genes. This work used a new protocol for practical and rapid extraction of plasmid DNA in order to characterize the plasmid patterns of Brazilian strains belonging to Embrapa Milho e Sorgo research center B. thuringiensis bank. We tried to further assess the relationship of plasmid patterns with strains belonging to the same serovars and strains causing 100% and no mortality to Spodoptera frugiperda (J.E. Smith) larvae. It was possible to characterize 59 strains based on the migration of bands in agarose gel. Strains belonging to the same serovars showed different plasmid sizes (from 1,636 bp to 23,200 bp), with the exception of two strains belonging to serovar galleriae. The strain T09 Bt tolworthi showed a plasmid migration pattern identical to strains belonging to serovar galleriae. Plasmid patterns differed for 46 strains, confirming that this is a useful tool to discriminate specific strains. However, it was not possible to associate the plasmid pattern or the occurrence of particular plasmids with the pathogenicity of a given species towards S. frugiperda larvae. PMID- 22068948 TI - Cost-effectiveness of integrated pest management compared with insecticidal spraying against the German cockroach in apartment buildings. AB - This study assessed the cost and effectiveness of an integrated pest management (IPM) program using hydramethylnon gel baits compared with conventional spraying for controlling the German cockroach, Blattella germanica (L.) (Blattodea: Blattellidae), in two residential buildings in Yasuj, Iran. The IPM approach was based on educational programs using pamphlets, posters and lectures, sanitation using vacuuming and application of hydramethylnon gel baits. Conventional approach used cypermethrin (10% EC) on baseboard and cracks-and-crevices. Sticky traps were used as tools for monitoring cockroach population densities. The IPM approach reduced (943%) the rate of insecticide application compared to the conventional spray. Cockroach populations in the IPM treatment were significantly reduced from an average of 12.2 +/- 3.01 cockroaches per unit before treatment to zero cockroach per unit by week four and thereafter. Cockroach populations in the conventional spray treatment were reduced from an average of 11.5 +/- 4.43 cockroaches per unit before treatment to an average of 3.4 +/- 0.99 cockroach per unit after 11 weeks of post treatment. The IPM treatment improved 100% of infested units compared to 78% for spray treatment to obtain a clean level of infestation (< 1cockroach per trap per unit). The results suggest that the intervention by IPM using hydramethylnon gel baits significantly reduced cockroach infestation compared to cypermethrin spray throughout the 11 weeks of post-treatment period. However, within the study period, the IPM system involving gel baits, educational program and sanitation was 363.2% more expensive than the conventional method. PMID- 22068949 TI - Infestation of cassava genotypes by Neosilba perezi (Romero & Ruppell) (Diptera: Lonchaeidae). AB - The objectives of this work were to assess the infestation of ten genotypes of cassava by the shoot fly Neosilba perezi (Romero & Ruppell) and to investigate effects of plant age, temperature or precipitation on cassava plants infestation by the shoot fly. Thirty-two individuals of each cassava genotype were planted and analyzed every two weeks in order to calculate the percentage of plants infested by shoot fly larvae at each sampling event and per genotype. Infestation by the fly was different across the genotypes. Genotype IAC Caapora 105-66 and genotype IAC Cascuda were resistant to shoot fly infestation, whereas the genotype IAC 15 was the most susceptible to this insect. Plant age may have an influence on infestation by shoot flies. Advanced plant age apparently favors lower or even inexistent infestation rates. However, infestation rate does not seem to be affected by temperature or precipitation. PMID- 22068950 TI - Natural incidence of egg parasitoids of Edessa meditabunda (F.) (Hemiptera: Pentatomidae) on Crotalaria spectabilis in Campo Novo do Parecis, MT, Brazil. AB - Egg parasitoids of the stink bug Edessa meditabunda (F) were studied on rattlepod Crotalaria spectabilis used in soybean crop rotation in Campo Novo do Parecis, Mato Grosso state, central western Brazil. Seven species of parasitoids were found: two Encyrtidae, one Eurytomidae, and four Platygastridae. The occurrence of Trissolcus euchisti (Ashmead) and Trissolcus elimatus Johnson (Platygastridae) on eggs of E. meditabunda is recorded for the first time. Moreover, this is the first record of T. elimatus and T. euchisti from Brazil. PMID- 22068951 TI - Record of Podisus nigrispinus (Dallas) (Hemiptera: Pentatomidae) preying on Metrogaleruca obscura Degeer (Coleoptera: Chrysomelidae). AB - Asopines are predators of insects, with several species with potential as biocontrol agents of a number of pests. Metrogaleruca obscura (Degeer), a neotropical species of Galerucini, was introduced in Malaysia, Asia, and Mauritius, Africa, to control the spread of Cordia curassavica (Boraginaceae), a native plant of the neotropics. The occurrence of Podisus nigrispinus (Dallas) preying on M. obscura is recorded, and Cordia verbenacea (Boraginaceae) is mentioned as a host plant for M. obscura. A list of Chrysomelidae attacked by asopines in the neotropical region is also presented. PMID- 22068952 TI - First record of the olive bud mite Oxycenus maxwelli (Keifer) (Acari: Eriophyidae) from Brazil. AB - The mite Oxycenus maxwelli (Keifer) (Eriophyidae) is reported for the first time in Brazil infesting olive trees, Olea europaea. Specimens were found on seedlings at Maria da Fe, state of Minas Gerais, in 2007. Although minor symptoms were not noticed, significant damage to plants were observed. There is no reliable evidence of when the mite could have been introduced. It is believed that the mite occurs since the first introductions of olive trees, around 1820, through vegetative propagating material, but the mite remained unnoticed due to the lack of studies with olive trees in Brazil. PMID- 22068953 TI - First host plant record for Pero obtusaria Prout (Lepidoptera: Geometridae). AB - The shrub Pluchea chingoyo is mentioned as the first host plant record for larvae of the little known moth Pero obtusaria Prout. PMID- 22068954 TI - New records of thrips (Thysanoptera) species in Brazil. AB - This study reports four thrips species from Brazil for the first time: the terebrantians Aptinothrips rufus (Haliday) and Echinothrips caribbeanus Hood; and the tubuliferans Androthrips ramachandrai Karny and Gynaikothrips uzeli (Zimmermann). New data about biological aspects of some of these new records are presented. PMID- 22068955 TI - Kamlet-taft and Catalan studies of some novel Y-shaped imidazole derivatives. AB - Some novel Y-shaped imidazole derivatives were developed and characterized by NMR and mass spectral techniques. The photophysical properties of these imidazole derivatives were studied in several solvents. The Kamlet-Taft and Catalan's solvent scales were found to be the most suitable for describing the solvatochromic shifts of the absorption and fluorescence emission. The adjusted coefficient representing the electron releasing ability or basicity of the solvent, C(beta) or C(SB) has a negative value, suggesting that the absorption and fluorescence bands shift to lower energies with the increasing electron donating ability of the solvent. This effect can be interpreted in terms of the stabilization of the resonance structures of the chromophore. The observed lower fluorescence quantum yield may be due to an increase in the non-radiative deactivation rate constant. This is attributed to the loss of planarity in the excited state provided by the non co-planarity of the cinnamaldehyde ring attached to C(2) atom of the imidazole ring. Such a geometrical change in the excited state leads to an important Stokes shift, reducing the reabsorption and reemission effects in the detected emission in highly concentrated solutions. PMID- 22068957 TI - Tumour-related factors and prognosis in breast cancer detected by screening. AB - BACKGROUND: Breast cancer detected by screening has an unexplained prognostic advantage beyond stage shift compared with cancers detected clinically. The aim was to investigate biological factors in invasive breast cancer, with reference to mode of detection and rate of death from breast cancer. METHODS: Histology, oestrogen receptor alpha and beta, progesterone receptor, human epidermal growth factor receptor (HER) 2, cyclin D1, p27, Ki-67 and perinodal growth were analysed in 466 tumours from a prospective cohort, the Malmo Diet and Cancer Study. Using logistic regression, odds ratios were calculated to investigate the relationship between tumour characteristics and mode of detection. The same tumour factors were analysed in relation to standard prognostic features. Death from breast cancer was analysed using Cox regression with adjustments for standard tumour factors; differences following adjustment were analysed by means of Freedman statistics. RESULTS: None of the biological tumour characteristics varied with mode of detection of breast cancer. After adjustment for age, tumour size, axillary lymph node involvement (ALNI) and grade, women with cancer detected clinically had an increased risk of death from breast cancer (hazard ratio 2.48, 95 per cent confidence interval 1.34 to 4.59), corresponding to a 37.2 per cent difference compared with the unadjusted model. Additional adjustment for biological tumour factors studied caused only minor changes. CONCLUSION: None of the biological tumour markers investigated explained the improved prognosis in breast cancer detected by screening. None of the factors was related to ALNI, suggesting that other mechanisms may be responsible for tumour spread. PMID- 22068956 TI - Spectrofluorimetric assessment of chlorzoxazone and ibuprofen in pharmaceutical formulations by using Eu-tetracycline HCl optical sensor doped in sol-gel matrix. AB - A novel, simple, sensitive and selective spectrofluorimetric method was developed for the determination of trace amounts of chlorzoxazone and Ibuprofen in pharmaceutical tablets using optical sensor Eu-Tetracycline HCl doped in sol-gel matrix. The chlorzoxazone or Ibuprofen can remarkably enhance the luminescence intensity of Eu-Tetracycline HCl complex doped in a sol-gel matrix in dimethylformamide (DMF) at pH 9.7 and 6.3, respectively, lambda(ex) = 400 nm. The enhancing of luminescence intensity peak of Eu-Tetracycline HCl complex at 617 nm is proportional to the concentration of chlorzoxazone or Ibuprofen a result that suggested profitable application as a simple optical sensor for chlorzoxazone or Ibuprofen assessment. The dynamic ranges found for the determination of chlorzoxazone and Ibuprofen concentration are 5 * 10(-9)-1 * 10(-4) and 1 * 10( 8)-7 * 10(-5) mol L(-1), and the limit of detection (LOD) and quantitation limit of detection (LOQ) are 3.1 * 10(-10), 9.6 * 10(-10) and 5.6 * 10(-10), 1.7 * 10( 9) mol L(-1), respectively. PMID- 22068958 TI - Water oxidation catalysed by manganese compounds: from complexes to 'biomimetic rocks'. AB - One of the most fundamental processes of the natural photosynthetic reaction sequence is the light-driven oxidation of water to molecular oxygen. In vivo, this reaction takes place in the large protein ensemble Photosystem II, where a MU-oxido-Mn(4)Ca- cluster, the oxygen-evolving-complex (OEC), has been identified as the catalytic site for the four-electron/four-proton redox reaction of water oxidation. This Perspective presents recent progress for three strategies which have been followed to prepare functional synthetic analogues of the OEC: (1) the synthesis of dinuclear manganese complexes designed to act as water-oxidation catalysts in homogeneous solution, (2) heterogeneous catalysts in the form of clay hybrids of such Mn(2)-complexes and (3) the preparation of manganese oxide particles of different compositions and morphologies. We discuss the key observations from the studies of such synthetic manganese systems in order to shed light upon the catalytic mechanism of natural water oxidation. Additionally, it is shown how research in this field has recently been motivated more and more by the prospect of finding efficient, robust and affordable catalysts for light driven water oxidation, a key reaction of artificial photosynthesis. As manganese is an abundant and non-toxic element, manganese compounds are very promising candidates for the extraction of reduction equivalents from water. These electrons could consecutively be fed into the synthesis of "solar fuels" such as hydrogen or methanol. PMID- 22068959 TI - Left ventricular diastolic function in type 2 diabetes mellitus is associated with myocardial triglyceride content but not with impaired myocardial perfusion reserve. AB - PURPOSE: To study myocardial perfusion reserve and myocellular metabolic alterations indicated by triglyceride content as possible causes of diastolic dysfunction in patients with type 2 diabetes mellitus, preserved systolic function, and without clinically evident coronary artery disease. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus (n = 42) underwent cardiac magnetic resonance (CMR) for quantification of 1) myocardial contractility by strain-encoded MR (SENC); 2) myocardial triglyceride content by proton magnetic resonance spectroscopy ((1) H-MRS); and 3) myocardial perfusion reserve during pharmacologic hyperemia. Age-matched healthy volunteers (n = 16) also underwent CMR to acquire normal values for myocardial strain and perfusion reserve. RESULTS: Stress CMR procedures were successfully performed in all subjects, and no regional inducible perfusion defects were observed in type 2 diabetes mellitus patients. Diastolic strain rate and myocardial perfusion reserve were significantly impaired in patients with type 2 diabetes mellitus compared to control subjects (P < 0.001 for both). Interestingly, impaired diastolic function in type 2 diabetes mellitus was not associated with impaired myocardial perfusion reserve (r = 0.12, P = NS). Conversely a significant association was observed between diastolic dysfunction and myocardial triglyceride content (r = -0.71, P < 0.001), which proved to be independent of age, gender, diabetes duration, blood pressure, and fasting blood glucose. CONCLUSION: Myocardial steatosis may represent an early marker of diabetic heart disease, triggering subclinical myocardial dysfunction irrespective of myocardial perfusion reserve. PMID- 22068960 TI - Design of thermostable luciferases through arginine saturation in solvent-exposed loops. AB - In most bioluminescence systems the oxidation of luciferin and production of light is catalyzed by luciferases. Protein engineering studies have shown that thermostable proteins from thermophilic organisms have a higher frequency of Arg, especially in exposed states. To further clarify the arginine saturation effect on thermostability of firefly luciferase, some of hydrophobic solvent-exposed residues in Lampyris turkestanicus luciferase are changed to arginine. All of these residues are located at the surface loops of L.turkestanicus luciferase. Starting with a luciferase mutant (E354Q/Arg356), single mutation (-Q35R, -I182R, -I232R and -L(300)R), double mutation (-Q35R/I232R) and triple mutation ( Q35R/I232R/I182R) are added. Bioluminescence emission spectra indicate that substitution of Arg by these residues, do not effect on the maximum wavelength of emission spectrum. It should be noted, introduction of double mutation ( Q35R/I232R) and triple mutation (-Q35R/I232R/I182R) were kept specific activity of firefly luciferase. By addition of positively charged residue, some specific mutations (-I232R, -Q35R/I232R and -Q35R/I232R/I182R) showed that optimum temperature of activity was increased to 40 degrees C which are 12 and 15 degrees C higher than E354Q/Arg356 and wild-type luciferases, respectively. Also, after 40 min incubation of enzymes at 40 degrees C, the relative remaining activity of wild type was only 5%, whereas for -I232R, -Q35R/I232R and -Q35R/I232R/I182R was 60, 80 and 80% of original activity, respectively. PMID- 22068961 TI - Unraveling the Helicobacter pylori UreG zinc binding site using X-ray absorption spectroscopy (XAS) and structural modeling. AB - The pathogenicity of Helicobacter pylori depends on the activity of urease for pH modification. Urease activity requires assembly of a dinickel active site that is facilitated in part by GTP hydrolysis by UreG. The proper functioning of Helicobacter pylori UreG (HpUreG) is dependent on Zn(II) binding and dimerization. X-ray absorption spectroscopy and structural modeling were used to elucidate the structure of the Zn(II) site in HpUreG. These studies independently indicated a site at the dimer interface that has trigonal bipyramidal geometry and is composed of two axial cysteines at 2.29(2) A, two equatorial histidines at 1.99(1) A, and a solvent-accessible coordination site. The final model for the Zn(II) site structure was determined by refining multiple-scattering extended X ray absorption fine structure fits using the geometry predicted by homology modeling and ab initio calculations. PMID- 22068962 TI - The differential heritability of personality item clusters. AB - An earlier twin analysis by Loehlin and Nichols was repeated with a considerably larger twin sample (2,600 adult Australian twin pairs). Like the previous analysis, it was based on item clusters, although from different questionnaires. Unlike the previous study, it found consistent differences in MZ-DZ discrepancy in correlation among the clusters. A more elaborate analysis confirmed this for the clusters, but not for broad Extraversion and Neuroticism composites based upon them. PMID- 22068963 TI - Nutritional aspects in patient undergoing liver resection. AB - In the past two decades, hepatic surgery has achieved important technical breakthroughs resulting in a drastic reduction of the onset of complications and in an improved post-resective survival. Pre-operative nutritional status is one of the key points for the success of a liver resection. Modern surgical achievement such as the development of living-related liver donation, and the possibility to perform more laparoscopic liver resection gave us the opportunity to extend post-operative protocol focused on early intestinal feeding to tumor patients. The aims of this review were to report the current status of the knowledge regarding nutritional aspects in liver resection patients. PMID- 22068964 TI - Glass etching to bridge micro- and nanofluidics. AB - In this study, a simple and economical fabrication technique bridging micro- and nanostructures is proposed. Glass molds with micro-nanostructures are fabricated by glass microlithography. The microlithography provides flexibility for structure design, and the glass etching contributes to transform the micro glass ridge to the nanoscale. Glass ridge structures with triangular cross sections are generated by undercutting, which coupled the isotropic character of glass and the shield effect of the top Cr layer upon HF etching. Further etching induced the height of the glass ridges to shrink from micro- to nanometres due to the edge effects. At the late etching stage, the geometrical change of the glass greatly slows down, which gives better control over the size of the glass ridge. By glass structure mold-copy, well repeatable, mechanically stable and tunable polydimethylsiloxane (PDMS) channels and cones are fabricated. Scanning electron microscopy (SEM) and laser interferometry (LI) are carried out to characterize the micro-nanostructures. To demonstrate their workability, sample preconcentration to a single nanochannel level is carried out. PMID- 22068965 TI - Work-related upper-extremity amputations in Norway. PMID- 22068967 TI - Acute enterocyte adaptation to luminal glucose: a posttranslational mechanism for rapid apical recruitment of the transporter GLUT2. AB - BACKGROUND: Glucose absorption postprandially increases markedly to levels far greater than possible by the classic glucose transporter sodium-glucose cotransporter 1 (SGLT1). HYPOTHESIS: Luminal concentrations of glucose >50 mM lead to rapid, phenotypic, non-genomic adaptations by the enterocyte to recruit another transporter, glucose transporter 2 (GLUT2), to the apical membrane to increase glucose absorption. METHODS: Isolated segments of jejunum were perfused in vivo with glucose-containing solutions in anesthetized rats. Carrier-mediated glucose uptake was measured in 10 and 100 mM glucose solutions (n = 6 rats each) with and without selective inhibitors of SGLT1 and GLUT2. RESULTS: The mean rate of carrier-mediated glucose uptake increased in rats perfused with 100 mM versus 10 mM glucose to 13.9 +/- 2.9 MUmol from 2.1 +/- 0.1 MUmol, respectively (p < 0.0001). Using selective inhibitors, the relative contribution of GLUT2 to glucose absorption was 56% in the 100 mM concentration of glucose compared to the 10 mM concentration (27%; p < 0.01). Passive absorption accounted for 6% of total glucose absorption at 100 mM glucose. CONCLUSION: A small amount of GLUT2 is active at the lesser luminal concentrations of glucose, but when exposed to concentrations of 100 mM, the enterocyte presumably changes its phenotype by recruiting GLUT2 apically to markedly augment glucose absorption. PMID- 22068968 TI - Imatinib mesylate improves liver regeneration and attenuates liver fibrogenesis in CCL4-treated mice. AB - BACKGROUNDS: Imatinib mesylate (STI-571), a tyrosine kinase inhibitor, has previously been demonstrated to attenuate liver fibrogenesis through inhibition of the activation of hepatic stellate cells (HSCs) in CCL(4)-treated rat models. AIMS: This study aimed to further evaluate the role of STI-571 in liver regeneration. MATERIALS AND METHODS: All animals were divided into four groups, and mice were treated with or without CCL(4) and STI-571 (n = 6 for each group). RESULTS: Activated cultured HSCs in vitro with STI-571 administration showed increased apoptosis and reduced proliferation, as determined by flow cytometric analysis, 3-(4, 5-cimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay, and confocal microscopy. STI-571 treatment attenuated liver fibrosis in vivo, as was evident in the results of histology, mRNA level, and expression analysis of smooth muscle actin and type I collagen. Mice treated with STI-571 had increased liver weight ratio and the improvement in liver regeneration was compatible with the change of serum interleukin 6 levels (p < 0.05). Further, increased apoptosis and a reduced proliferation were observed in the CCL(4)-treated mice after STI 571 treatment based on the immunohistochemical staining of Annexin V, phosphorylated STAT3, and PCNA. CONCLUSION: STI-571 treatment effectively attenuated liver fibrogenesis and improved in liver regeneration in vivo and induced apoptosis in HSCs both in vitro and in vivo. PMID- 22068969 TI - Timing and risk factors of hepatectomy in the management of complications following laparoscopic cholecystectomy. AB - INTRODUCTION: Complex bile duct injury (BDI) is a serious condition requiring hepatectomy in some instances. The present study was to analyse the factors that led to hepatectomy for patients with BDI after laparoscopic cholecystectomy (LC). METHODS: The medical records of patients referred to our department from April 1998 to September 2007 for management of BDI following LC were reviewed, and patients who underwent hepatectomy were identified. The type of BDI, indication for liver resection, interval between LC and liver surgery, histology of the liver specimen, postoperative morbidity and long-term results were analysed. RESULTS: Hepatectomy was performed in 10 of 76 patients (13.2%), with BDI either as isolated damage or in combination with vascular injury (VI). Proximal BDI (defined as disruption of the biliary confluence) and injury to the right hepatic artery were found to be independent risk factors of hepatectomy, with odds ratios of 16 and 45, respectively. Five patients required early liver resection (within 5 weeks post-LC) to control sepsis caused by confluent liver necrosis or bile duct necrosis. In five patients, hepatectomy was indicated during long-term follow-up (over 4 months post-LC) to effectively manage recurrent cholangitis and liver atrophy. Despite of high postoperative morbidity (60%) and even mortality (10%), the long-term results (median follow-up of 34 months) were satisfactory, with either no or only transitory symptoms in 67% of the patients. CONCLUSION: Hepatectomy may inevitably be necessary to manage early or late complications after LC. Proximal BDI and VI were the two independent risk factors of hepatectomy in this series. PMID- 22068970 TI - Littoral cell angioma and angiosarcoma of the spleen: report of two cases in siblings and review of the literature. PMID- 22068971 TI - A systematic review of the accuracy and clinical utility of the Addenbrooke's Cognitive Examination and the Addenbrooke's Cognitive Examination-Revised in the diagnosis of dementia. AB - OBJECTIVES: To review the evidence relating to the diagnostic accuracy and clinical utility of the Addenbrooke's Cognitive Examination (ACE) and its updated version, the Addenbrooke's Cognitive Examination-Revised (ACE-R) in relation to the diagnosis of dementia. DESIGN: A systematic search of relevant databases was conducted, covering the period 2000 to April 2010. Specific journals and reference lists were hand searched. Identified studies that fulfilled the inclusion criteria were reviewed using a tailored, methodological quality rating checklist. RESULTS: The systematic search process identified nine studies for review (seven relating to the ACE, two on the ACE-R). Strengths and weaknesses across studies are considered, and diagnostic accuracy measures are presented for six out of the nine studies. CONCLUSION: The evidence suggests that the ACE/ACE-R is capable of providing information on a range of cognitive domains and of differentiating well between those with and those without cognitive impairment. Further research examining how the tools distinguish between dementia subtypes and mild cognitive impairment will further benefit the evidence base. PMID- 22068973 TI - Functionalization of two-component molecular networks: recognition of Fe3+. AB - Two-component supramolecular networks have been constructed with a symmetric triphenylene derivative with three carboxyl groups (sym-TTT) and melamine. Two kinds of hydrogen bonds with different strength are involved in the multi component self-assembly, one is H-bond between carboxyl group of sym-TTT and melamine, the other is intermolecular H-bond between melamine molecules. These interactions drive a structural transformation from close-packed network to hexagonal network with active amino groups inside of the cavity. Scanning tunneling microscopy (STM) measurements reveal that the functionalized network of sym-TTT/melamine could recognise Fe(3+). These results could be helpful for designing functionalized molecular networks by multi-component self-assembling strategy. PMID- 22068972 TI - Calcium control of neurotransmitter release. AB - Upon entering a presynaptic terminal, an action potential opens Ca(2+) channels, and transiently increases the local Ca(2+) concentration at the presynaptic active zone. Ca(2+) then triggers neurotransmitter release within a few hundred microseconds by activating synaptotagmins Ca(2+). Synaptotagmins bind Ca(2+) via two C2-domains, and transduce the Ca(2+) signal into a nanomechanical activation of the membrane fusion machinery; this activation is mediated by the Ca(2+) dependent interaction of the synaptotagmin C2-domains with phospholipids and SNARE proteins. In triggering exocytosis, synaptotagmins do not act alone, but require an obligatory cofactor called complexin, a small protein that binds to SNARE complexes and simultaneously activates and clamps the SNARE complexes, thereby positioning the SNARE complexes for subsequent synaptotagmin action. The conserved function of synaptotagmins and complexins operates generally in most, if not all, Ca(2+)-regulated forms of exocytosis throughout the body in addition to synaptic vesicle exocytosis, including in the degranulation of mast cells, acrosome exocytosis in sperm cells, hormone secretion from endocrine cells, and neuropeptide release. PMID- 22068974 TI - The Meaning In Life Questionnaire: psychometric properties with individuals with serious mental illness in an inpatient setting. AB - OBJECTIVES: This study examined the psychometric properties of the Meaning in Life Questionnaire (MLQ) with individuals with serious mental illness (SMI) in an inpatient setting (N = 96). The 10-item MLQ comprises Presence (perceived meaning) and Search (motivation to discover meaning) scales. DESIGN: This study focused on the reliability and validity of the MLQ, reporting a range of data, including correlations and regression (predicting scores on a measure of psychopathology, the Brief Symptom Inventory). RESULTS: Both MLQ scales yielded reliable scores. The current sample tended to report greater Presence, whereas Search means tended to be similar to those reported in other studies. The association between Presence and the Brief Symptom Inventory was not statistically significant. As for Search, people reporting greater motivation to discover meaning tended to report greater degrees of symptoms. The Presence and Search scales correlated at r =.12, which was unexpected given that most studies note an inverse relationship. However, this finding is considered in light of an interaction effect between Presence and Search when predicting psychological distress. CONCLUSIONS: The current findings are supportive of the MLQ's utility with individuals with SMI. Limitations and directions for research are offered. PMID- 22068975 TI - Mutagenesis of the thiostrepton precursor peptide at Thr7 impacts both biosynthesis and function. AB - The seventh residue of thiostrepton is predicted to be critical for antibacterial activity. Substitution of Thr7 in the thiostrepton precursor peptide disrupts both biological activity and the successful biosynthesis of analogs. PMID- 22068976 TI - Pattern formation in the iodate-sulfite-thiosulfate reaction-diffusion system. AB - Sodium polyacrylate-induced pH pattern formation and starch-induced iodine pattern formation were investigated in the iodate-sulfite-thiosulfate (IST) reaction in a one-side fed disc gel reactor (OSFR). As binding agents of the autocatalyst of hydrogen ions or iodide ions, different content of sodium polyacrylate or starch has induced various types of pattern formation. We observed pH pulses, striped patterns, mixed spots and stripes, and hexagonal spots upon increasing the content of sodium polyacrylate and observed iodine pulses, branched patterns, and labyrinthine patterns upon increasing the starch content in the system. Coexistence of a pH front and an iodine front was also studied in a batch IST reaction-diffusion system. Both pH and iodine front instabilities were observed in the presence of sodium polyacrylate, i.e., cellular fronts and transient Turing structures resulting from the decrease in diffusion coefficients of activators. The mechanism of multiple feedback may explain the different patterns in the IST reaction-diffusion system. PMID- 22068977 TI - Rapid improvement of tardive dyskinesia with tetrabenazine, clonazepam and clozapine combined: a naturalistic long-term follow-up study. AB - Tardive dyskinesia (TD) is a complex involuntary movement disorder affecting about 23% of neuroleptic-treated patients. Our objective was to retrospectively analyze a combination of tetrabenazine (TBZ), clonazepam (CLONAZ) and clozapine (CLOZ) used simultaneously for TD in psychotic patients. Six patients with severe, unsuccessfully controlled TD were referred for treatment (mean age 51.5 years; three male; four schizophrenics; one bipolar disease; one borderline personality disorder). They were being treated with neuroleptics (classic, three; risperidone, two; olanzapine, one) and developed severe neck and buccolingual dyskinesias. At our clinic, all of them were treated simultaneously with TBZ (mean dose 141.6 mg); CLONAZ (mean dose 4.3 mg); and CLOZ (mean dose 125 mg). In parallel, we stopped the offending medication. With 1 week, we observed a very impressive improvement in symptoms and within 1 month all the patients were free of symptoms. The mean observation period was 4 years. The combination of TBZ, CLONAZ and CLOZ is a rapid and beneficial option for the management of TD. An augmentation effect probably played a role in the rapid alleviation of symptomatology. PMID- 22068978 TI - The flexible FIGO classification concept for underlying causes of abnormal uterine bleeding. AB - To this juncture, clinical management, teaching of medical providers, and the design and interpretation of clinical trials has been hampered by the absence of a consensus system for the classification of causes or potential causes of abnormal uterine bleeding (AUB). Indeed, more than one possible mechanism may be involved in the development of the bleeding symptoms experienced by a given individual. A consistent and universally accepted classification system could be used by clinicians, investigators, and even patients to facilitate communication, clinical care, and research. The "PALM-COEIN" AUB classification system is the result of several years of collaboration among a spectrum of individuals involved in clinical medicine, teaching, and the basic and clinical sciences and is proposed as a tool that meets the requirements just described but one that is capable of adaptation to our evolving insight into the mechanisms involved in the genesis of AUB. This system has been accepted by the International Federation of Gynecology and Obstetrics (FIGO) as a suitable system for widespread international use. PMID- 22068980 TI - The Escherichia coli protein YfeX functions as a porphyrinogen oxidase, not a heme dechelatase. AB - The protein YfeX from Escherichia coli has been proposed to be essential for the process of iron removal from heme by carrying out a dechelation of heme without cleavage of the porphyrin macrocycle. Since this proposed reaction is unique and would represent the first instance of the biological dechelation of heme, we undertook to characterize YfeX. Our data reveal that YfeX effectively decolorizes the dyes alizarin red and Cibacron blue F3GA and has peroxidase activity with pyrogallal but not guiacol. YfeX oxidizes protoporphyrinogen to protoporphyrin in vitro. However, we were unable to detect any dechelation of heme to free porphyrin with purified YfeX or in cellular extracts of E. coli overexpressing YfeX. Additionally, Vibrio fischeri, an organism that can utilize heme as an iron source when grown under iron limitation, is able to grow with heme as the sole source of iron when its YfeX homolog is absent. Plasmid-driven expression of YfeX in V. fischeri grown with heme did not result in accumulation of protoporphyrin. We propose that YfeX is a typical dye-decolorizing peroxidase (or DyP) and not a dechelatase. The protoporphyrin reported to accumulate when YfeX is overexpressed in E. coli likely arises from the intracellular oxidation of endogenously synthesized protoporphyrinogen and not from dechelation of exogenously supplied heme. Bioinformatic analysis of bacterial YfeX homologs does not identify any connection with iron acquisition but does suggest links to anaerobic-growth related respiratory pathways. Additionally, some genes encoding homologs of YfeX have tight association with genes encoding a bacterial cytoplasmic encapsulating protein. IMPORTANCE: Acquisition of iron from the host during infection is a limiting factor for growth and survival of pathogens. Host heme is the major source of iron in infections, and pathogenic bacteria have evolved complex mechanisms to acquire heme and abstract the iron from heme. Recently Letoffe et al. (Proc. Natl. Acad. Sci. U.S.A. 106:11719-11724, 2009) reported that the protein YfeX from E. coli is able to dechelate heme to remove iron and leave an intact tetrapyrrole. This is totally unlike any other described biological system for iron removal from heme and, thus, would represent a dramatically new feature with potentially profound implications for our understanding of bacterial pathogenesis. Given that this reaction has no precedent in biological systems, we characterized YfeX and a related protein. Our data clearly demonstrate that YfeX is not a dechelatase as reported but is a peroxidase that oxidizes endogenous porphyrinogens to porphyrins. PMID- 22068981 TI - Mononuclear-dinuclear equilibrium of grafted copper complexes confined in the nanochannels of MCM-41 silica. AB - Following the structural concept of copper-containing proteins in which dinuclear copper centers are connected by hydroxide bridging ligands, a bidentate copper(II) complex has been incorporated into nano-confined MCM-41 silica by a multistep sequential grafting technique. Characterization by a combination of EPR spectroscopy, X-ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, IR spectroscopy , and solid-state (13)C and (29)Si cross-polarization magic-angle spinning (CP-MAS) NMR suggests that dinuclear Cu complexes are bridged by hydroxide and other counterions (chloride or perchlorate ions), similar to the situation for EPR-undetectable [Cu(II)...Cu(II)] dimer analogues in biological systems. More importantly, a dynamic mononuclear-dinuclear equilibrium between different coordination modes of copper is observed, which strongly depends on the nature of the counterions (Cl(-) or ClO(4)(-)) in the copper precursor and the pore size of the silica matrix (the so-called confinement effect). A proton transfer mechanism within the hydrogen-bonding network is suggested to explain the dynamic nature of the dinuclear copper complex supported on the MCM-41 silica. PMID- 22068979 TI - A monomorphic haplotype of chromosome Ia is associated with widespread success in clonal and nonclonal populations of Toxoplasma gondii. AB - Toxoplasma gondii is a common parasite of animals that also causes a zoonotic infection in humans. Previous studies have revealed a strongly clonal population structure that is shared between North America and Europe, while South American strains show greater genetic diversity and evidence of sexual recombination. The common inheritance of a monomorphic version of chromosome Ia (referred to as ChrIa*) among three clonal lineages from North America and Europe suggests that inheritance of this chromosome might underlie their recent clonal expansion. To further examine the diversity and distribution of ChrIa, we have analyzed additional strains with greater geographic diversity. Our findings reveal that the same haplotype of ChrIa* is found in the clonal lineages from North America and Europe and in older lineages in South America, where sexual recombination is more common. Although lineages from all three continents harbor the same conserved ChrIa* haplotype, strains from North America and Europe are genetically separate from those in South America, and these respective geographic regions show limited evidence of recent mixing. Genome-wide, array-based profiling of polymorphisms provided evidence for an ancestral flow from particular older southern lineages that gave rise to the clonal lineages now dominant in the north. Collectively, these data indicate that ChrIa* is widespread among nonclonal strains in South America and has more recently been associated with clonal expansion of specific lineages in North America and Europe. These findings have significant implications for the spread of genetic loci influencing transmission and virulence in pathogen populations. IMPORTANCE: Understanding parasite population structure is important for evaluating the potential spread of pathogenicity determinants between different geographic regions. Examining the genetic makeup of different isolates of Toxoplasma gondii from around the world revealed that chromosome Ia is highly homogeneous among lineages that predominate on different continents and within genomes that were otherwise quite divergent. This pattern of recent shared ancestry is highly unusual and suggests that some gene(s) found on this chromosome imparts an unusual fitness advantage that has resulted in its recent spread. Although the basis for the conservation of this particularly homogeneous chromosome is unknown, it may have implications for the transmission of infection and spread of human disease. PMID- 22068982 TI - The cover. The last of New England--the beginning of New Mexico. PMID- 22068983 TI - A piece of my mind. Annie. PMID- 22068984 TI - Public health cuts threaten preparedness, preventive health services. PMID- 22068985 TI - Nobel Prize honors immunity researchers. PMID- 22068986 TI - Knockout science: massive mouse project to provide window into human diseases. PMID- 22068987 TI - Pegloticase and chronic gout. PMID- 22068988 TI - Microscopic hematuria in adolescents and young adults and risk for end-stage renal disease. PMID- 22068989 TI - Reporting of effect direction and size in abstracts of systematic reviews. PMID- 22068991 TI - Association between physician billing and cardiac stress testing patterns following coronary revascularization. AB - CONTEXT: The degree to which financial factors may influence use of cardiac stress imaging procedures is unknown. OBJECTIVE: To examine the association of physician billing and nuclear stress and stress echocardiography testing following coronary revascularization. DESIGN, SETTING, AND PATIENTS: Using data from a national health insurance carrier, 17,847 patients were identified between November 1, 2004, and June 30, 2007, who had coronary revascularization and an index cardiac outpatient visit more than 90 days following the procedure. Based on overall billings, physicians were classified as billing for both technical (practice/equipment) and professional (supervision/interpretation) fees, professional fees only, or not billing for either. Logistic regression models were used to evaluate the association between physician billing and use of stress testing, after adjusting for patient and other physician factors. MAIN OUTCOME MEASURES: Incidence of nuclear and echocardiographic stress tests within 30 days of an index cardiac-related outpatient visit. RESULTS: The overall cumulative incidence of nuclear or echocardiography stress testing within 30 days of the index cardiac-related outpatient visit following revascularization was 12.2% (95% CI, 11.8%-12.7%). The cumulative incidence of nuclear stress testing was 12.6% (95% CI, 12.0%-13.2%), 8.8% (95% CI, 7.5%-10.2%), and 5.0% (95% CI, 4.4%-5.7%) among physicians who billed for technical and professional fees, professional fees only, or neither, respectively. For stress echocardiography, the cumulative incidence of testing was 2.8% (95% CI, 2.5%-3.2%), 1.4% (95% CI, 1.0%-1.9%), and 0.4% (95% CI, 0.3%-0.6%) among physicians who billed for the technical and professional fees, professional fees only, or neither, respectively. Adjusted odds ratios (ORs) of nuclear stress testing among patients treated by physicians who billed for technical and professional fees and professional fees only were 2.3 (95% CI, 1.8-2.9) and 1.6 (95% CI, 1.2-2.1), respectively, compared with those patients treated by physicians who did not bill for testing (P < .001). The adjusted OR of stress echocardiography testing among patients treated by physicians billing for both or professional fees only were 12.8 (95% CI, 7.6 21.6) and 7.1 (95% CI, 4.0-12.9), respectively, compared with patients treated by physicians who did not bill for testing (P < .001). CONCLUSION: Nuclear stress testing and stress echocardiography testing following revascularization were more frequent among patients treated by physicians who billed for technical fees, professional fees, or both compared with those treated by physicians who did not bill for these services. PMID- 22068992 TI - Neuron number and size in prefrontal cortex of children with autism. AB - CONTEXT: Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. OBJECTIVE: To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES: Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. MAIN OUTCOME MEASURES: Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. RESULTS: Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, -8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. CONCLUSION: In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC. PMID- 22068993 TI - Treatment of brain arteriovenous malformations: a systematic review and meta analysis. AB - CONTEXT: Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies. OBJECTIVES: To assess rates of case fatality, long term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes. DATA SOURCES: We searched PubMed and EMBASE to March 1, 2011, and hand-searched 6 journals from January 2000 until March 2011. STUDY SELECTION AND DATA EXTRACTION: We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration. DATA SYNTHESIS: We identified 137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43 0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00 1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996). Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization. Successful brain AVM obliteration was achieved in 96% (range, 0% 100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization. CONCLUSIONS: Although case fatality after treatment has decreased over time, treatment of brain AVM remains associated with considerable risks and incomplete efficacy. Randomized controlled trials comparing different treatment modalities appear justified. PMID- 22068994 TI - Can the Patient-Centered Outcomes Research Institute become relevant to controlling medical costs and improving value? PMID- 22068995 TI - Narrative vs evidence-based medicine--and, not or. PMID- 22068996 TI - Linking insurance coverage for innovative invasive procedures with participation in clinical research. PMID- 22068997 TI - Acute stroke therapy at the crossroads. PMID- 22068998 TI - Financial incentives and the art of payment reform. PMID- 22068999 TI - Increased neuron number and head size in autism. PMID- 22069000 TI - JAMA patient page. Chronic sinusitis. PMID- 22069001 TI - [Glucocorticoids in individual prescriptions]. PMID- 22068990 TI - Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial. AB - CONTEXT: Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically. OBJECTIVE: To test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia. DESIGN: Parallel-group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002 to 2010. SETTING: Forty-nine clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers. PARTICIPANTS: Patients with arteriographically confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. Of 195 patients who were randomized, 97 were randomized to receive surgery and 98 to no surgery. Follow-up for the primary end point until occurrence, 2 years, or termination of trial was 99% complete. No participant withdrew because of adverse events. INTERVENTIONS: Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Antithrombotic therapy and risk factor intervention were recommended for all participants. MAIN OUTCOME MEASURE: For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days after surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery, the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within 2 years of randomization. RESULTS: The trial was terminated early for futility. Two-year rates for the primary end point were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%; 20 events) for the nonsurgical group (P = .78, Z test), a difference of 1.7% (95% CI, -10.4% to 13.8%). Thirty-day rates for ipsilateral ischemic stroke were 14.4% (14/97) in the surgical group and 2.0% (2/98) in the nonsurgical group, a difference of 12.4% (95% CI, 4.9% to 19.9%). CONCLUSION: Among participants with recently symptomatic AICAO and hemodynamic cerebral ischemia, EC-IC bypass surgery plus medical therapy compared with medical therapy alone did not reduce the risk of recurrent ipsilateral ischemic stroke at 2 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00029146. PMID- 22069002 TI - [Dermato-epidemiology]. AB - Dermato-epidemiology is an important scientific discipline which investigates skin diseases using epidemiological methods. Epidemiology is the science of the distribution and determinants of disease in specified populations. We describe fundamental terms of dermato-epidemiology (measures of disease occurrence, measures of risk), different study types (observational studies, interventional studies), the selection of statistical tests, bias and confounding as well as the principles of evidence-based dermatology, and give illustrative examples. PMID- 22069004 TI - The Revista Brasileira de Epidemiologia (Brazilian Journal of Epidemiology-RBE) has followed the increase in scientific production in the field of public health and epidemiology. PMID- 22069005 TI - [Evaluation of the Brazilian surveillance system for adverse events following vaccination]. AB - OBJECTIVES: To describe and evaluate the Brazilian system of passive surveillance of adverse events following immunization (PSAEFI). METHODS: The description and evaluation of PSAEFI were undertaken using the reported cases of adverse events following immunization with DTwP-Hib vaccine (AEFI-T), during the period from 2002 to 2005, using the Centers for Disease Control methodology. RESULTS: The PSAEFI system, which provides national coverage, is designed to standardize practices in cases of adverse events following immunization (AEFI) and to identify highly reactogenic lots of vaccine. The PSAEFI system proved its usefulness, simplicity and flexibility; despite low sensitivity, overestimate the proportion of sever events, but it consistently described AEFI-T, identifying fever, convulsions and hypotonic-hyporesponsive episodes as the most common events. It showed that 49.7% of AEFI-T occur after the first dose, and that 72.8% occur within the first six hours after vaccination. It facilitates public health decisions and epidemiological investigations. It is timely, 46.1% of all AEFI-T being reported within 10 days after vaccination and its completeness ranges from 70 to 90%, depending on the item evaluated. CONCLUSIONS: The PSAEFI system proved useful for monitoring DTwP-Hib vaccine safety. We recommended the incorporation of new methodologies, such the use of sentinel cities/hospitals and computerized immunization registries in order to increase its sensitivity. PMID- 22069006 TI - [A socio-economic profile of exposed populations to petroleum exploration residues]. AB - INTRODUCTION: Environmental Macro-Area Five (EMA-5) is located in Rio de Janeiro. Their municipalities are suffering the consequences of rapid urbanization, especially after the discovery of large reserves of petroleum and natural gas (PNG) in the Campos Basin. OBJECTIVE: To describe the socio-economic profile of the region and compare their indicators in space and time. METHODS: This is an ecological study, which made comparisons between the 11 municipalities of EMA-5. It is based on the behavior of the indicators before and after the increase in royalties and special participatioms (RPE) and the division of the production areas of PNG (main production area - MPA - and the border zone of MPA, BZMPA). The period of analysis of the indicators ranged from 1991 to 2005. RESULTS: Higher values of gross domestic product per capita were found in the municipalities of MPA, especially Macae. The same occurred in the RPE per capita, especially Rio das Ostras (higher value) and Nova Friburgo (lower value). In 2004, more than 50% of total revenues of municipalities were dependent on the funds derived from royalties. In 2000, Nova Friburgo had the best Human Development Index. The highest value of the Quality Index of Municipalities Potential for Development was found in Macae. The major indexes of Social Exclusion was found in Macae, Nova Friburgo and Rio das Ostras. CONCLUSION: It was found, in the municipalities of MPA, economic growth with great exclusive reliance on royalties. It should invest in alternative economic activities for which there is no damage to the population with the completion of these resources. PMID- 22069007 TI - [Migration and Hansen's disease in Mato Grosso]. AB - Studies on medical geography about leprosy discuss the role of the detailed report of the occupation of the territories as a basis of the permanence of leprosy focus. In Brazil, the states that present the highest rates of detection historically are in the Amazon region, which shows an uneven regional evolution of the disease. This paper analyzes the evolution of leprosy contextualizing the migratory processes that occurred in the State of Mato Grosso since the second half of the 20th century. The economic dynamism that occurred in the State in the 1970s, 1980s and 1990s caused population growth rates higher than the national average. The data analyzed permitted an association between the evolution of leprosy and the process of occupation of the mato-grossense territory. However, the permanence of leprosy in the municipalities of the Baixada Cuiabana, as well as in other municipalities that lost population, seem to point to the existence of geographic contexts of different vulnerability to the social production of the disease in the tate. The migration would explain the appearance and evolution of leprosy. However, we consider that the maintenance of the endemic can be associated to contextual factors related to environment. PMID- 22069008 TI - [Household appliances and food insecurity: gender, referred skin color and socioeconomic differences]. AB - OBJECTIVE: Data from the National Household Survey 2004 was analyzed to compare differences in prevalence among moderate or severe food insecurity. Also, it was compared food security or mild food insecurity households in relation to the assets and other socioeconomic and demographic conditions of the household. METHOD: Private permanent households, with per capita monthly income of up to one minimum wage and with the Brazilian Food Insecurity Scale answered by a household resident were studied (n=51,357). Association of variables with the dependent variable (food security) was verified using chi2 test, with 5% significance level. Crude prevalence ratio, respective 95% confidence interval and adjusted analyses were carried out using Poisson multiple regression Stata 8.0. It considers the weights of the complex sampling design of the survey. RESULTS: The per capita monthly household income was the variable with strongest association to food security. Both in urban and rural areas, there were higher risk of moderate or severe food insecurity prevalence ratio when the head of the household was a female, black color, presence of six or more members in the household, metropolitan area and with absence of some specific assets (stove, water filter, refrigerator, freezer, washing machine and cellular phone). In a model that, among assets, included just the refrigerator, it was observed the highest prevalence ratio for household income of up to 1/4 of a minimum wage and after this, the absence of refrigerator among households headed by white and black males and white or black female. Although female and black headed households have greater food restriction, internal differences among these groups were higher for households headed by white males and lower for those headed by black females. CONCLUSION: At national level and households with monthly income of up to one minimum age, poor socioeconomic conditions are associated to household food insecurity. This situation is worse among those headed by women and black people. Among poor people, the absence of assets identifies the most vulnerable population to food insecurity and may be used as complementary indicator, mainly in local studies with poor technical resources for data collection and more sophisticated analyzes. PMID- 22069009 TI - [Hospital admissions in the hospital health care system, SUS and non-SUS: Brazil, 2006]. AB - The objective of this study was to analyze admissions in the hospital health care system in Brazil in the year of 2006, starting from the admitted subjects. The initial data were the admissions SUS (SIH), non-SUS (CIH) in 2006 and 2007. The identification of the individual was by probabilistic method of associations of registrations (linkage) and, for the composition of the admission data, specific algorithms were applied to the data. A total of 12,391,990 admissions with at least one day in hospital in the year of 2006 were analyzed. The imprecise nature of the probabilistic method at a certain degree, the adoption of conservative parameters in order to avoid the inclusion of false positive, and the subnotification of CIH represent possible limitations of this study. The Hospital Services System in Brazil presented admission rate of 5.6% in total, 5.0% SUS and 1.6% non-SUS, with differences according to age and region. The non-SUS admissions data collected by CIH give important additional information to the analysis of the hospital utilization in the country. The SUS administrative data are valid for analyses of admissions and the algorithms for admission data composition enhance the analysis of the Hospital Services System in Brazil. PMID- 22069010 TI - [Internet behavior survey about the unprotected anal sex with men who have sex with men]. AB - INTRODUCTION: Unprotected anal sex (insertive or receptive) is an important risk factor for HIV infection and other STDs. OBJECTIVE: The objective was to investigate individual and social factors associated with unprotected anal sex among Men Who have Sex with Men (MSM) that declared being HIV negative and engaged in anal sex with an HIV positive partner or of ignored serology. METHODS: This study is part of a survey among MSM and among Internet users, with data collected from an on line questionnaire in project site. The internet sample for this study was 487 MSM. Descriptive and stratified analyses were carried out and chi2 test was used. Logistic regression was used for modeling the data. RESULTS: Among the participants 30.8% referred unprotected anal sex in the previous 12 months with an HIV positive partner or partner with unknown serology. Most of them belonged to higher social classes, were white and single. Factors associated with unprotected anal sex were: number of partners (more than 3) in the previous 12 months (OR=1.7; 95% CI 1.1-2.7), high or medium perception of risk to HIV/Aids (OR=2.7; 95% CI 1.5-3.6) and enjoy passive oral sex (OR=0.3; 95% CI 0.2-0.8). CONCLUSION: Unprotected anal sex was a frequent practice among MSM in this survey. The frequency to public bathrooms should be further explored as a risk factor for unprotected anal sex. It is important to further explore these findings in order to understand these relationships and the involvement in risky sexual practices for HIV infection among MSM. PMID- 22069011 TI - [Motorcycle couriers: characteristics of traffic accidents in southern Brazil]. AB - OBJECTIVE: This study aimed at understanding characteristics of traffic accidents with motorcycle couriers in the cities of Londrina and Maringa, in the State of Parana (Brazil). METHODS: A total of 327 couriers who reported, in 2005/2006, motorcycle accident in the previous 12 months took part in the study (147 in Londrina and 180 in Maringa). RESULTS: Of all the interviewed, 39.6% reported more than one traffic accident. The accidents were perceived as serious by 21.4% of them and 56.3% reported knowing a convalescing courier due to a traffic accident. Most injuries (82.9%) occurred during work hours. Significant differences were observed between the cities concerning climatic conditions (p=0.013), time of the day (p=0.002), pre-hospital care (p=0.032) and hospital admission (p<0.001). CONCLUSION: The high incidence and the recurrence of traffic accidents highlight the susceptibility of motorcycle couriers to these events and the need for strategies and specific prevention policies. PMID- 22069012 TI - [Traffic related air pollution and population health: a review about Sao Paulo (SP), Brazil]. AB - INTRODUCTION: Air pollution is an important problem for Sao Paulo city and vehicles are the main source. About 11 million people are exposed to this pollution. OBJECTIVE: To examine studies realized about air pollution and its effects on health of the population of Sao Paulo (Brazil) and methods of assessing exposure to pollution related to traffic. METHODS: We performed a literature review using the keywords "air pollution", "Sao Paulo", and traffic related air pollution. RESULTS: As results were obtained several studies that found relation between air pollution in Sao Paulo and respiratory and cardiovascular problems, fetal growth, increased mortality and hospitalizations, particularly in children and elderly people. In order to estimate the exposure, most of these studies consider the isotropic distribution of pollutants throughout the area, what prevents the evaluation of and the influence of traffic. Several methods have been used to analyze the air traffic exposure, which can be used isolated or combined. It is believed that the combination of models used to calculate pollutant concentrations to methods of georeferencing is the most appropriate approach for similar studies in Sao Paulo. The advantages of these methods are the ability to identify priority areas and situations, obtaining detailed information for adoption of public policies or measures, and to simulate different scenarios. CONCLUSION: The application of these methods in studies at Sao Paulo depends on the improvement of input data, air quality meteorological monitoring net enhancement and data of traffic volume. PMID- 22069013 TI - [Challenges in definition of gestational age in population studies on birth preterm: the case of a study in Campina Grande (PB), Brazil]. AB - INTRODUCTION: The prevalence of preterm birth has increased in recent years and it is currently a worldwide public health problem. In any epidemiological study, the greatest challenge facing the study of preterm delivery is to standardize the measurement of gestational age births. OBJECTIVE: To describe the methods used to define the sample under study and selection of events in case-control studies of risk factors for preterm birth in hospital births by mothers living in the city of Campina Grande (PB), Brazil. METHODS: The design was a case-control population based, which was conducted from June 2008 to May 2009. The cases were born at less than 37 weeks of gestation and controls at 37 weeks or more. Gestational age in weeks was defined using selection criteria based on the accuracy of the estimate. Interviews were conducted with mothers and collection of hospital records. RESULTS: It was selected 341 cases and 424 controls, 13.19% were classified as extremely preterm (<28 weeks), 34.87% as very preterm (<33 weeks) and 65.10% as moderate preterm (33 to 36 weeks of gestation). Among controls, the percent of children born 37-39 weeks was 58.02 to 5.90% was born post term (>42 weeks). CONCLUSION: The strategies shown to be viable, even in a context with major limitations in obtaining the necessary information, given that the profile of preterm infants, the distribution of gestational age were comparable to studies with more accurate methods. PMID- 22069014 TI - [Early diagnosis and correlations of sexually transmitted infections among women in primary care health services]. AB - INTRODUCTION: Sexually Transmitted Infections (STIs) in women remain a public health challenge due to high prevalence, difficulties to implement early diagnosis strategies and high rates of complications. OBJECTIVE: Identify the prevalence of STIs among users of a primary health care clinic in Sao Paulo. METHODS: Women, 18 to 40 years of age, were invited to self-collect vaginal specimens to be tested for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis by Polymerase Chain Reaction (PCR). Women were also invited to answer a demographic and sexual history questionnaire, either on the computer or face-to-face. RESULTS: The prevalence of STIs obtained from the 781 women included in the study was: Chlamydia trachomatis: 8.4%, Neisseria gonorrhoeae: 1.9%, and Trichomonas vaginalis: 3.2%. Thirteen percent tested positive for at least one out of the three STIs. The variables associated independently with a higher risk of STIs were: age under 20-years-old, more than two lifetime sexual partners, and self-perception of STI risk. The use of condoms as a contraceptive method proved to be a protective factor. CONCLUSION: The high prevalence found among these women indicates the need for the implementation of STI screening strategies in primary care settings in Brazil. PMID- 22069015 TI - [Tuberculosis treatment drop out prevalence and associated factors in Sapucaia do Sul County (RS), Brazil, 2000-2008]. AB - OBJECTIVE: To estimate the Tuberculosis treatment drop out prevalence and the variables associated in the patients registered in the Tuberculosis Control Program in Sapucaia do Sul (Brazil), between 2000 and 2008. METHOD: A cross sectional study was conducted, which was based on the notified data in Information System for Disease Surveillance of the City Health Secretariat. RESULTS: From the 632 cases included in the study, 65 (10.3%; CI95%=7.9-12.7) were classified as treatment abandonment. Between 2000 and 2004, the prevalence of noncompliance was 12.7% (95%CI=9.1-16.2), and in the period 2005 to 2008 decreased to 7.0% (95%CI=4.0-9.9). In the crude analysis, we find association with sex, age and AIDS presence. The adjusted analysis with the Poisson regression didn't show significant differences between the independent variables. CONCLUSION: The analysis showed reduction in the prevalence of noncompliance with the creation of Tuberculosis Control Program, from 2005, although the confidence intervals are shown superimposed. Still, the prevalence of noncompliance was high and stove above the 5% target, agreed between levels of government. PMID- 22069016 TI - [Latent tuberculosis among professionals with and without direct contact with inmates of two penitentiaries in the state of Sao Paulo, Brazil, 2008]. AB - INTRODUCTION: For groups of persons who remain confined, mainly in prisons, tuberculosis has always been a serious health problem, due to its transmission respiratory, putting in risk the professionals that work in a prison, especially the communicants of inmates. OBJECTIVE: To know the infection prevalence for the Mycobacterium tuberculosis among the employees communicating and no communicating of inmates of two prisons of the State of Sao Paulo. METHODS: This study consisted of the application of an individual questionnaire; application and reading of the tuberculin skin testing (TST); sputum smear examination and culture; identification and drug sensitivity testing; in the period of March the June of 2008. RESULTS: 277 (48.3%) employees of the 574 existent were examined. They were applied and read 248 (89.5%) TST (PPD-RT23 - 2TU/0.1 mL); of them, 194 were in employees that worked directly with the inmates, that is, were communicants and 54 were no communicants. Among the communicants, 62.4% presented induration larger than 10 mm and among the non communicants, 38.9% presented this measure of TST. There was not positive in the sputum smear examination or in the culture, that is, tuberculosis illness case was not identified enters the professionals, at the moment of the research. CONCLUSION: This study suggests that the communicant employees have a larger risk of if they infect for the M. tuberculosis and consequently of being sick of tuberculosis. PMID- 22069017 TI - [Population based study on periodontal conditions and socioeconomic determinants in adults in the city of Guarulhos (SP), Brazil, 2006]. AB - OBJECTIVE: This study described the prevalence of periodontal conditions and assessed its association with social, economical and behavioral variables in adults aged 35 to 44 years old, residents in the city of Guarulhos, State of Sao Paulo, 2006. METHODS: This study was a population based survey with cluster sampling. Data collecting and exams were done at houses drew at random. The Community Periodontal Index was used to assess the periodontal condition. Data analysis used EPIINFO 6 and STATA 10 softwares. The assessment of association used the prevalence ratio (PR), as calculated by Poisson regression models with complex sampling and weighted sample adjustments. RESULTS: The total number of people was 263 in 237 domiciles. In the multivariate model, the prevalence of gingival bleeding and dental calculus was significantly associated to being male (PR=1.12, p=0.04), smoking (PR=1.11, p=0.01), school level of less than eight years of study (PR=1.14, p=0.01), and who have not received dental care for more than two years (PR=1.19, p<0.01). As for the presence of periodontal pocket, associated factors were smoking (PR=1.71, p=0.02) and who have not received dental care for more than 2 years (PR=1.97, p=0.03). CONCLUSION: We observed a higher prevalence (62.7%) of individuals with gingival bleeding and dental calculus in relation to the presence of shallow or deep periodontal pockets (26,6%). As shallow pockets are reversible, their treatment may be resolute in programs of primary dental care. PMID- 22069018 TI - [Translation and validation for Brazil of the body image scale for adolescents- Offer Self-Image Questionnaire (OSIQ)]. AB - OBJECTIVE: To evaluate the semantic and measure equivalence of the body image sub scale of the Offer Self Image Questionnaire (OSIQ). METHODS: Participants were 386 teenagers, 10 to 18 years old, both sexes, enrolled in a private school (junior and high school age). Translation, back-translation, technique revision and evaluation were conducted. The Portuguese instrument was evaluated for internal consistency, discriminate and concurrent validity. RESULTS: Internal consistency showed values from 0.43 to 0.54 and was able to discriminate all groups studied--the whole population, boys and girls, and boys in early adolescence, by nutritional status (p<0.001; p<0.009; p=0.030; p=0.043, respectively). Concurrent analyses showed significant correlation with anthropometric measures only for girls (r=-0.16 and p=0.021; r=-0.19 and p=0.007), early adolescence (r=-0.23 and p=0.008; r=-0.26 and p=0.003) and intermediate adolescence (r=-0.29 and p=0.010) and the retest confirmed reliability by the coefficient of interclass correlation. Although the instrument has proven its ability to discriminate between the groups studied by nutritional state, other results were less satisfactory. More studies are necessary for full transcultural adaptation, including the application of other comparative scales. CONCLUSION: The body image sub-scale of the OSIQ was translated, but the results are not promising and require more studies. PMID- 22069019 TI - [Mortality by race/color: evidence of social inequalities in Vitoria (ES), Brazil]. AB - OBJECTIVE: To analyze mortality by cause and sex among groups of race or color from the mortality information system (MIS) in Vitoria (Brazil), in the period from 2003 to 2006. METHODS: We calculated and analyzed the mortality rates according to underlying cause, sex and race/color, and the mean and median age of death by underlying cause, sex and race. We calculated the relative risk (RR) for age, sex and underlying cause (p<0.05 and CI 95%). RESULTS: The completeness of race/color in SIM ranged from 1% in 1996 to 81% in 2006. There was a greater RR of death among blacks for mental and behavioral disorders (RR=9.29), Ill-defined causes (RR=8.71), and external causes (RR=5.71). For black women, we highlight the external causes (RR=2.38). We found a variation of up to 33 years (nervous system) between whites and blacks. CONCLUSION: This study confirms the existence of unequal racial/ethnic mortality, highlighting the mortality from mental disorders and external causes, in addition to early mortality that occurs in the black population. PMID- 22069020 TI - [Food groups for the investigation of risk of type 2 diabetes and associated diseases]. AB - INTRODUCTION: The food groups conventionally applied in activities of nutritional counseling were established according to their macronutrient content. However, it does not consider recent scientific evidences of the association between food consumption and risk of developing non-communicable chronic diseases. OBJECTIVE: To propose food groups for the investigation of the association between food consumption and risk of developing type 2 diabetes and associated diseases among Japanese-Brazilians. METHODS: Cross-sectional analysis of baseline data of a lifestyle intervention study conducted among Japanese-Brazilians of Bauru, SP, Brazil, from 2005 to 2007. Food intake was assessed by three 24-hour recalls of 640 participants, both genders, aged 30 to 88 years old. RESULTS: Eighteen new food groups were proposed according to their quantity and quality of fat, carbohydrates, sodium, and fiber. CONCLUSION: The new food groups incorporate recent evidences of the association between diet and the risk of developing type 2 diabetes. PMID- 22069022 TI - Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation. AB - BACKGROUND: Management of inflammatory bowel disease (IBD) is increasingly focused on mucosal remission. We assessed the prevalence of mucosal inflammation during clinical remission, the clinical consequences, and the impact on disease course. METHODS: IBD patients from two referral centers who underwent a surveillance colonoscopy while clinically in remission between January 2001 and December 2003 were included. Follow-up ended May 1, 2009. Clinical data were collected from patient charts. Statistical analysis was performed using independent t-tests and nonparametric tests. RESULTS: In total, 152 IBD patients were included (98 [65%] ulcerative colitis, 46 [30%] Crohn's disease; 85 [56%] males). Median follow-up was 6.8 years (interquartile range [IQR] 6-8). Forty seven (31%) patients had no signs of inflammation during endoscopy (group A). Of the remaining 105 (68%) patients, 51 (49%) had both endoscopic and histological inflammation (group B), 51 (49%) histological inflammation only (group C), two (2%) endoscopic lesions only (group D). Two years later, 29% of all patients had endoscopic inflammation and another 27% had only microscopic inflammation. In 39% the inflammation had resolved spontaneously. Inflammation was more often found in group B+C (n = 62/102; 61%) than in group A (n = 17/47; 36%; P = 0.21). Inflammation was not associated with more frequent clinical relapses nor with stricture formation, nor with the need for surgery. CONCLUSIONS: A large proportion of IBD patients have mucosal inflammation without clinical symptoms. Although one-third recover spontaneously, mucosal inflammation in patients who are clinically in remission is associated with more severe mucosal disease activity, but not with more complications or symptomatic flares during follow-up. PMID- 22069024 TI - Chiral anion-based NMR enantiodiscrimination of a dinuclear, cationic Ir(I) NHC complex with a figure-of-eight loop structure. AB - A dinuclear Ir(I) complex with a bis-NHC ligand was formed in situ from 1,1' ((4,6-dimethyl-1,3-phenylene)bis(methylene))bis(3-methyl-1H-imidazol-3-ium) in the presence of Cs(2)CO(3) and [Ir(MU-Cl)(cod)](2). Its solid-state structure, determined by X-ray diffraction, shows a figure-of-eight loop with both the P and M enantiomers being present. Solution NMR studies were performed to examine the enantiodiscrimination between them by applying the enantiopure anions tris(tetrachlorobenzenediolato)phosphate(v) (Delta-TRISPHAT) and bis(tetrachlorobenzenediolato)mono([1,10]binaphthalenyl-2,20-diolato)phosphate(v) (Lambda-BINPHAT). PMID- 22069023 TI - Predictors of medication adherence in an urban Latino community with healthcare disparities. AB - Ethnic disparities exist when comparing glycemic control: Latino patients have suboptimal glycemic control as compared to non-Latino whites. A key factor to achieving optimal diabetes management and control is medication adherence. We conducted a nested, cross-sectional retrospective study of data (n = 61) collected from a larger parallel, randomized, longitudinal study conducted at an urban primary care practice examining a culturally tailored community-based peer counselor intervention. Baseline demographic and medication utilization covariates were evaluated for eligibility into the multivariate logistic regression to predict medication adherence. Significant correlates of medication adherence were physician or healthcare team support (OR 12.79, 95% CI 1.04, 157.21), and increasing numbers of medications taken (OR 1.24, 95% CI 1.04, 1.48). Receipt of government benefits was associated with medication non adherence (OR 0.06, 95% CI 0.01, 0.51). Modifiable factors such as the number of medications and the patient-healthcare team relationship appear to play a role in medication adherence. PMID- 22069025 TI - Mass-forming autoimmune pancreatitis and pancreatic carcinoma: differential diagnosis on the basis of computed tomography and magnetic resonance cholangiopancreatography, and diffusion-weighted imaging findings. AB - PURPOSE: To differentiate mass-forming autoimmune pancreatitis (AIP) from pancreatic carcinoma by means of analysis of both computed tomography (CT) and magnetic resonance imaging (MRI) findings. MATERIALS AND METHODS: Ten patients with mass-forming AIP diagnosed by revised clinical criteria of Japan Pancreas Society and 70 patients with pathologically proven pancreatic carcinoma were enrolled in this retrospective study. Two radiologists independently evaluated the CT and MR imaging findings. The sensitivity, specificity, and odds ratio of significant imaging findings and combinations of findings were calculated. RESULTS: Seven findings were more frequently observed in AIP patients: (i) early homogeneous good enhancement, (ii) delayed homogeneous good enhancement, (iii) hypoattenuating capsule-like rim, (iv) absence of distal pancreatic atrophy, (v5) duct penetrating sign, (vi) main pancreatic duct (MPD) upstream dilatation <= 4 mm, and (vii) an apparent diffusion coefficient (ADC) <= 0.88 * 10(-3) mm(2) /s. When the findings of delayed homogeneous enhancement and ADC <= 0.88 * 10(-3) mm(2) /s were both used in diagnosis of mass-forming AIP, a sensitivity of 100% and a specificity of 100% were achieved. When 4 of any of the 7 findings were used in the diagnosis of AIP, a sensitivity of 100% and a specificity of 98% were achieved. CONCLUSION: Analysis of a combination of CT and MR imaging findings allows for highly accurate differentiation between mass-forming AIP and pancreatic carcinoma. PMID- 22069026 TI - Cloning of a fibrinolytic enzyme (subtilisin) gene from Bacillus subtilis in Escherichia coli. AB - Several investigations are being pursued to enhance the efficacy and specificity of fibrinolytic therapy. In this regard, microbial fibrinolytic enzymes attracted much more medical interests during these decades. Subtilisin, a member of subtilases (the superfamily of subtilisin-like serine proteases) and also a fibrinolytic enzyme is quite common in Gram-positive bacteria, and Bacillus species stand out in particular, as many extracellular and even intracellular variants have been identified. In the present work, the subtilisin gene from Bacillus subtilis PTCC 1023 was cloned into the vector pET-15b and expressed in Escherichia coli strain BL21 (DE3). Total genomic DNA were isolated and used for PCR amplification of the subtilisin gene by means of the specific primers. SDS PAGE and enzyme assay were done for characterizing the expressed protein. A ~1,100 bp of the structural subtilisin gene was amplified. The DNA and amino acid sequence alignments resulting from the BLAST search of subtilisin showed high sequence identity with the other strains of B. subtilis, whereas significantly lower identity was observed with other bacterial subtilisins. The recombinant enzyme had the same molecular weight as other reported subtilisins and the E. coli transformants showed high subtilisin activity. This study provides evidence that subtilisin can be actively expressed in E. coli. The commercial availability of subtilisin is of great importance for industrial applications and also pharmaceutical purposes as thrombolytic agent. Thus, the characterization of new recombinant subtilisin and the development of rapid, simple, and effective production methods are not only of academic interest, but also of practical importance. PMID- 22069027 TI - Biogenic synthesis of multidimensional gold nanoparticles assisted by Streptomyces hygroscopicus and its electrochemical and antibacterial properties. AB - The fabrication of reliable, green chemistry processes for nanomaterial synthesis is an important aspect of nanotechnology. The biosynthesis of single-pot room temperature reduction of aqueous chloroaurate ions by Streptomyces hygroscopicus cells has been reported to facilitate the development of an industrially viable greener methodology for the synthesis of technologically important gold nanoparticles (AuNPs). Multidimensional AuNPs are generated via the manipulation of key growth parameters, including solution pH and reaction time. The synthesized nanostructures are characterized by UV/Vis and energy dispersive X ray analysis studies. Particle morphology is characterized by HRTEM, FE-SEM and BioAFM. Additionally, we have demonstrated the electrochemical and antibacterial properties of AuNPs via cyclic voltammetry analysis and a minimal inhibitory concentration assay. Owing to the drawbacks of chemical synthesis, a biological synthesis method has been developed to generate biocompatible, inexpensive and eco-friendly size-controlled nanoparticles. PMID- 22069028 TI - Quiescin sulfhydryl oxidase (QSOX) is expressed in the human atheroma core: possible role in apoptosis. AB - Quiescin sulfhydryl oxidases (QSOXs) catalyze the formation of disulfide bonds in peptides and proteins, and in vertebrates comprise two proteins: QSOX1 and QSOX2. QSOX1, the most extensively studied type, has been implicated in protein folding, production of extracellular matrix, redox regulation, protection from apoptosis, angiogenesis, and cell differentiation. Atherosclerosis is an immunopathological condition in which redox processes, apoptosis, cell differentiation, and matrix secretion/maturation have critical roles. Considering these data, we hypothesized that QSOX1 could be involved in this disease, possibly reducing apoptosis and angiogenesis inside the plaque. QSOX1 labeling in normal human carotid vessels showed predominant expression by endothelium, subendothelium, and adventitia. In atherosclerotic plaques, however, QSOX1 was highly expressed in macrophages at the lipid core. QSOX1 expression was also studied in terms of mRNA and protein in cell types present in plaques under apoptotic or activating stimuli, emulating conditions found in the atherosclerotic process. QSOX1 mRNA increased in endothelial cells and macrophages after the induction of apoptosis. At the protein level, the correlation between apoptosis and QSOX1 expression was not evident in all cell types, possibly because of a rapid secretion of QSOX1. Our results propose for the first time possible roles for QSOX1 in atherosclerosis, being upregulated in endothelial cells and macrophages by apoptosis and cell activation, and possibly controlling these processes, as well as angiogenesis. The quantitative differences in QSOX1 induction may depend on the cell type and also on local factors. PMID- 22069029 TI - Hit clustering can improve virtual fragment screening: CDK2 and PARP1 case studies. AB - Virtual fragment screening could be a promising alternative to existing experimental screening techniques. However, reliable methods of in silico fragment screening are yet to be established and validated. In order to develop such an approach we first checked how successful the existing molecular docking methods can be in predicting fragment binding affinities and poses. Using our Lead Finder docking software the RMSD of the binding energy prediction was observed to be 1.35 kcal/mol(-1) on a set of 26 experimentally characterized fragment inhibitors, and the RMSD of the predicted binding pose from the experimental one was <1.5 A. Then, we explored docking of 68 fragments obtained from 39 drug molecules for which co-crystal structures were available from the PDB. It appeared that fragments that participate in oriented non-covalent interactions, such as hydrogen bonds and metal coordination, could be correctly docked in 70-80% of cases suggesting the potential success of rediscovering of corresponding drugs by in silico fragment approach. Based on these findings we've developed a virtual fragment screening technique which involved structural filtration of protein-ligand complexes for specific interactions and subsequent clustering in order to minimize the number of preferable starting fragment candidates. Application of this method led to 2 millimolar-scale fragment PARP1 inhibitors with a new scaffold. PMID- 22069030 TI - Comparative homology modeling of pyruvate dehydrogenase kinase isozymes from Xenopus tropicalis reveals structural basis for their subfunctionalization. AB - Structural-functional divergence is responsible for the preservation of highly homologous genes. Protein functions affected by mutagenesis in divergent sequences require investigation on an individual basis. In the present study, comparative homology modeling and predictive bioinformatics analysis were used to reveal for the first time the subfunctionalization of two pyruvate dehydrogenase kinase (PDK) isozymes in the western clawed frog Xenopus tropicalis. Three dimensional structures of the two proteins were built by homology modeling based on the crystal structures of mammalian PDKs. A detailed comparison of them revealed important structural differences that modify the accessibility of the nucleotide binding site in the two isozymes. Based on the generated models and bioinformatics data analysis, the differences between the two proteins in terms of kinetic parameters, metabolic regulation, and tissue distribution are predicted. The results obtained are consistent with the idea that one of the xtPDKs is the major isozyme responsible for metabolic control of PDC activity in X. tropicalis, whereas the other one has more specialized functions. Hence, this study provides a rationale for the existence of two closely related PDK isozymes in X. tropicalis, thereby enhancing our understanding of the functional evolution of PDK family genes. PMID- 22069031 TI - Evaluation of ultrasound-guided diagnostic local anaesthetic hip joint injection for osteoarthritis. AB - PURPOSE: The diagnosis of hip osteoarthritis is often complicated by co-existing pathology in the knee and spine, and mismatch between clinical and radiological signs. Temporary pain relief from a local anaesthetic injection into the hip joint has been reported to help localise symptoms, reducing the risk of unnecessary surgery being performed. We hypothesize that good surgical outcome is predicted by good analgesia following diagnostic injection, and that alternative pathology is present when there is no response to injection. METHODS: Data were analysed from a prospective database of 163 consecutive patients who underwent diagnostic hip injection for possible osteoarthritis. We recorded result of injection and whether hip arthroplasty was performed. A good outcome to surgery was defined as subsequent pain relief without significant residual symptoms. RESULTS: A total of 138 patients were suitable for inclusion in the study. Fifty eight patients had hip arthroplasty following a good response to diagnostic injection. Of these 54 had a good outcome following surgery (93%). There was also a quantitative improvement in pain and function in these patients as measured by 1 year post-operative and pre-operative Harris hip scores (P < 0.0001). A total of 44/49 patients had no surgery following no response to injection. A clear alternative diagnosis to hip osteoarthritis was made in 40 of these patients (91%). CONCLUSION: Diagnostic ultrasound-guided local anaesthetic injection of the hip joint is a useful test in confirming hip pathology. Complete relief of hip pain following intracapsular injection of local anaesthetic is associated with good surgical outcome following joint replacement. PMID- 22069032 TI - High resolution magnetic resonance imaging of the patellar retinaculum: normal anatomy, common injury patterns, and pathologies. AB - The medial patellar retinaculum (MPR) and the lateral patellar retinaculum (LPR) are vital structures for the stability of the patella. Failure to identify or treat injury to the patellar retinaculum is associated with recurrent patellar instability and contributes to significant morbidity. High-resolution magnetic resonance imaging (MRI) readily depicts the detailed anatomy of various components (layers) of the retinacula. In this review article, we discuss normal anatomy, important landmarks, common injury patterns, and other pathologies encountered in patellar retinacula. High field strength MRI is an excellent noninvasive tool for evaluation of patellar retinaculum anatomy and pathology. This article will help the reader become familiar with normal imaging findings and the most commonly occurring injuries/pathologies in MPR and LPR. PMID- 22069033 TI - Muscle fat-fraction and mapping in Duchenne muscular dystrophy: evaluation of disease distribution and correlation with clinical assessments. Preliminary experience. AB - PURPOSE: To examine the usefulness of dual-echo dual-flip angle spoiled gradient recalled (SPGR) magnetic resonance imaging (MRI) technique in quantifying muscle fat fraction (MFF) of pelvic and thighs muscles as a marker of disease severity in boys with Duchenne muscular dystrophy (DMD), by correlating MFF calculation with clinical assessments. We also tried to identify characteristic patterns of disease distribution. MATERIALS AND METHODS: Twenty consecutive boys (mean age, 8.6 years +/- 2.3 [standard deviation, SD]; age range, 5-15 years; median age, 9 years;) with DMD were evaluated using a dual-echo dual-flip angle SPGR MRI technique, calculating muscle fat fraction (MFF) of eight muscles in the pelvic girdle and thigh (gluteus maximus, adductor magnus, rectus femoris, vastus lateralis, vastus medialis, biceps femoris, semitendinosus, and gracilis). Color coded parametric maps of MFF were also obtained. A neurologist who was blinded to the MRI findings performed the clinical assessments (patient age, Medical Research Council score, timed Gower score, time to run 10 m). The relationships between mean MFF and clinical assessments were investigated using Spearman's rho coefficient. Positive and negative correlations were evaluated and considered significant if the P value was < 0.05. RESULTS: The highest mean MFF was found in the gluteus maximus (mean, 46.3 % +/- 24.5 SD), whereas the lowest was found in the gracilis muscle (mean, 2.7 % +/- 4.7 SD). Mean MFF of the gluteus maximus was significantly higher than that of the other muscles (P < 0.01), except for the adductor magnus and biceps muscles. A significant positive correlation was found between the mean MFF of all muscles and the patients age (20 patients; P < 0.005), Medical Research Council score (19 patients; P < 0.001), timed Gower score (17 patients; P < 0.03), and time to run 10 m (20 patients; P < 0.001). A positive correlation was also found between the mean MFF of the gluteus maximus muscle and the timed Gower score. Color-coded maps provided an efficient visual assessment of muscle fat content and its heterogeneous distribution. CONCLUSION: Muscle fat fraction calculation and mapping using the dual-echo dual-flip angle SPGR MRI technique are useful markers of disease severity and permit patterns of disease distribution to be identified in patients with DMD. PMID- 22069035 TI - Automated tertiary structure prediction with accurate local model quality assessment using the IntFOLD-TS method. AB - The IntFOLD-TS method was developed according to the guiding principle that the model quality assessment (QA) would be the most critical stage for our template based modeling pipeline. Thus, the IntFOLD-TS method firstly generates numerous alternate models, using in-house versions of several different sequence-structure alignment methods, which are then ranked in terms of global quality using our top performing QA method-ModFOLDclust2. In addition to the predicted global quality scores, the predictions of local errors are also provided in the resulting coordinate files, using scores that represent the predicted deviation of each residue in the model from the equivalent residue in the native structure. The IntFOLD-TS method was found to generate high quality 3D models for many of the CASP9 targets, whilst also providing highly accurate predictions of their per residue errors. This important information may help to make the 3D models that are produced by the IntFOLD-TS method more useful for guiding future experimental work. PMID- 22069034 TI - Assessment of protein structure refinement in CASP9. AB - We assess performance in the structure refinement category in CASP9. Two years after CASP8, the performance of the best groups has not improved. There are few groups that improve any of our assessment scores with statistical significance. Some predictors, however, are able to consistently improve the physicality of the models. Although we cannot identify any clear bottleneck in improving refinement, several points arise: (1) The refinement portion of CASP has too few targets to make many statistically meaningful conclusions. (2) Predictors are usually very conservative, limiting the possibility of large improvements in models. (3) No group is actually able to correctly rank their five submissions-indicating that potentially better models may be discarded. (4) Different sampling strategies work better for different refinement problems; there is no single strategy that works on all targets. In general, conservative strategies do better, while the greatest improvements come from more adventurous sampling-at the cost of consistency. Comparison with experimental data reveals aspects not captured by comparison to a single structure. In particular, we show that improvement in backbone geometry does not always mean better agreement with experimental data. Finally, we demonstrate that even given the current challenges facing refinement, the refined models are useful for solving the crystallographic phase problem through molecular replacement. Proteins 2011;. (c) 2011 Wiley-Liss, Inc. PMID- 22069037 TI - Identification of "known unknowns" utilizing accurate mass data and ChemSpider. AB - In many cases, an unknown to an investigator is actually known in the chemical literature, a reference database, or an internet resource. We refer to these types of compounds as "known unknowns." ChemSpider is a very valuable internet database of known compounds useful in the identification of these types of compounds in commercial, environmental, forensic, and natural product samples. The database contains over 26 million entries from hundreds of data sources and is provided as a free resource to the community. Accurate mass mass spectrometry data is used to query the database by either elemental composition or a monoisotopic mass. Searching by elemental composition is the preferred approach. However, it is often difficult to determine a unique elemental composition for compounds with molecular weights greater than 600 Da. In these cases, searching by the monoisotopic mass is advantageous. In either case, the search results are refined by sorting the number of references associated with each compound in descending order. This raises the most useful candidates to the top of the list for further evaluation. These approaches were shown to be successful in identifying "known unknowns" noted in our laboratory and for compounds of interest to others. PMID- 22069036 TI - Automated protein structure modeling in CASP9 by I-TASSER pipeline combined with QUARK-based ab initio folding and FG-MD-based structure refinement. AB - I-TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and fragment-guided molecular dynamics (FG-MD), were added to the I-TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I-TASSER structure assembly simulations. FG-MD is an atomic-level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen-bonding networks, torsion angles, and steric clashes. Despite considerable progress in both the template-based and template-free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of beta-proteins are still needed to further improve the I-TASSER pipeline. PMID- 22069038 TI - Studying interfacial reactions of cholesterol sulfate in an unsaturated phosphatidylglycerol layer with ozone using field induced droplet ionization mass spectrometry. AB - Field-induced droplet ionization (FIDI) is a recently developed ionization technique that can transfer ions from the surface of microliter droplets to the gas phase intact. The air-liquid interfacial reactions of cholesterol sulfate (CholSO(4)) in a 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) surfactant layer with ozone (O(3)) are investigated using field-induced droplet ionization mass spectrometry (FIDI-MS). Time-resolved studies of interfacial ozonolysis of CholSO(4) reveal that water plays an important role in forming oxygenated products. An epoxide derivative is observed as a major product of CholSO(4) oxidation in the FIDI-MS spectrum after exposure of the droplet to O(3) for 5 s. The abundance of the epoxide product then decreases with continued O(3) exposure as the finite number of water molecules at the air-liquid interface becomes exhausted. Competitive oxidation of CholSO(4) and POPG is observed when they are present together in a lipid surfactant layer at the air-liquid interface. Competitive reactions of CholSO(4) and POPG with O(3) suggest that CholSO(4) is present with POPG as a well-mixed interfacial layer. Compared with CholSO(4) and POPG alone, the overall ozonolysis rates of both CholSO(4) and POPG are reduced in a mixed layer, suggesting the double bonds of both molecules are shielded by additional hydrocarbons from one another. Molecular dynamics simulations of a monolayer comprising POPG and CholSO(4) correlate well with experimental observations and provide a detailed picture of the interactions between CholSO(4), lipids, and water molecules in the interfacial region. PMID- 22069039 TI - New electric-shock job exposure matrix. AB - BACKGROUND: To evaluate a consistent association between jobs in "electric" occupations and amyotrophic lateral sclerosis (ALS), a comprehensive job exposure matrix (JEM) that includes electric shocks and magnetic fields (MF) is needed. METHODS: We used incident electric shocks and electrocutions from two available data sources along with expert judgment to create a JEM that was integrated into an existing MF JEM. The final JEM contained ordinal electric-shock exposure assignments for 501 job titles. RESULTS: Main occupational groups experiencing the electric shocks were precision production, craft, and repair occupations. Specific jobs with the highest proportion of shocks per 100,000 workers were: electrical apprentices (99.7), mechanic and repairer helpers (74.0), hoist and winch operators (63.3), and electrical power installers (52.4). Examples of job titles with low electric-shock exposures were administrative support occupations, data-key entry operators, and waiters and waitresses. CONCLUSIONS: Combining publicly available data with an expert panel is a viable method to construct an electric-shock MF JEM. This JEM will allow an evaluation of association between electric shocks and neurodegenerative diseases. PMID- 22069040 TI - Loss of epithelial oestrogen receptor alpha inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models. AB - Squamous metaplasia (SQM) is a specific phenotype in response to oestrogen in the prostate and oestrogen receptor (ER) alpha is required to mediate this response. Previous studies utilizing tissue recombination with seminal vesicle (SV) mesenchyme and prostatic ductal tips from wild type and ERalphaKO mice suggested that both epithelial and stromal ERalpha are necessary for SQM. However, tissue recombination is conducted in the renal capsule of immune-deficient mice, in which the microenvironment is different from normal prostate microenvironment in the intact mice. Furthermore, whether the requirement of stromal ERalpha in the SV for developing SQM is the same as in the prostate is unknown. Therefore, there is a clear need to evaluate the respective roles of ERalpha in prostate epithelial versus stromal compartments in the intact mouse. Here we generated a mouse model that has selectively lost ERalpha in either stromal (FSP-ERalphaKO) or epithelial prostate cells (pes-ERalphaKO) to determine the requirements of ERalpha for oestrogen-stimulated prostate proliferation and SQM. Our results indicated that FSP-ERalphaKO prostates develop full and uniform SQM, which suggests that loss of the majority (~65%) of stromal ERalpha will not influence oestrogen-mediated SQM. In contrast, loss of epithelial ERalpha inhibits oestrogen-mediated prostate growth and SQM evidenced by decreasing cytokertin 10 positive squamous cell stratification and differentiation, by reduced ERalpha protein expression in SQM compared to wild type mice ERalpha, and by the presence of normal proliferative activities in the oestrogen-treated pes-ERalphaKO prostates. These in vivo results suggest that epithelial ERalpha is required for oestrogen-mediated proliferative response and could be an appropriate target for preventing aberrant oestrogen signalling in the prostate. PMID- 22069041 TI - ParaCEST MRI contrast agents capable of derivatization via"click" chemistry. AB - A comprehensive series of lanthanide chelates has been prepared with a tetrapropargyl DOTAM type ligand. The complexes have been characterized by a combination of (1)H NMR, single-crystal X-ray crystallography, CEST and relaxation studies and have also been evaluated for potential use as paramagnetic chemical exchange saturation transfer (ParaCEST) contrast agents in magnetic resonance imaging (MRI). We demonstrate the functionalization of several chelates by means of alkyne-azide "click" chemistry in which a glucosyl azide is used to produce a tetra-substituted carbohydrate-decorated lanthanide complex. The carbohydrate periphery of the chelates has a potent influence on the CEST properties as described herein. PMID- 22069042 TI - Malignant pheochromocytoma: new malignancy criteria. AB - PURPOSE: The pathological diagnosis of malignancy in pheochromocytomas remains a controversial issue. According to the WHO, malignancy is defined in the presence of metastasis. Multiparameter scoring systems such as PASS (Pheochromocytoma of Adrenal gland Scaled Score) have been used but remain controversial. The aim of this study was to search for new immunohistologic elements allowing determination of pheochromocytoma malignancy. METHODS: Among 53 patients operated for pheochromocytoma between 1993 and 2009, we selected pheochromocytomas with proven metastasis, seven cases in group 1 (G1) and paired two others groups: group 2 (G2), patients who had "benign" pheochromocytoma with PASS >=4 and group 3 (G3), patients who had "benign" pheochromocytoma with PASS <4. We retrospectively analysed PASS criteria, size, weight, tumour necrosis, Ki-67 and pS100 staining. RESULTS: The size and weight of the lesion were directly and significantly correlated to malignancy in all three groups: respectively 9.7 cm and 292.0 g (G1), 6.2 cm and 83.8 g (G2) and 3.8 cm and 37.1 g (G3) (p < 0.005 for both). Tumour necrosis (TN) was present in all G1 (p < 0.005) and respectively at 0% and 37.5% in G2 and G3. Ki-67 is directly correlated to presence of TN (p < 0.005) and malignancy (G1 14.1%, G2 1.8%, G3 2.6%; p < 0.001). All G1 had a Ki-67 index >4%, although one G3 presented an 11% Ki-67 index. There was an inverse statistically significant correlation between the three groups in staining using pS100 (p < 0.01). CONCLUSIONS: Size and weight of the pheochromocytoma are directly related to PASS and malignancy. The presence of tumour necrosis, Ki-67 index >4% and pS100 absence impose a close histopathological evaluation and follow-up with regard to cases presenting a high risk of malignancy/recurrence. PMID- 22069043 TI - Adrenocortical carcinoma: effect of hospital volume on patient outcome. AB - PURPOSE: Optimal management of adrenocortical carcinoma (ACC) involves a detailed diagnostic workup, radical surgery, and appropriate adjuvant therapy. However, due to the rarity of this disease, adequate expertise is necessary to ensure optimal patient care. We evaluated if the experience of a treating center influences the outcome of ACC. METHODS: Two hundred sixty-three patients who underwent adrenalectomy for ACC were included in a multi-institutional surgical survey and divided into 2 groups: "high-volume center" (HVC) (>=10 adrenalectomies for ACC) and "low-volume center" (LVC) (<10 adrenalectomies for ACC). A comparative analysis was performed. RESULTS: One hundred seventy-two patients underwent adrenalectomy at HVC and 91 at LVC. The two groups were homogeneous for age, sex, clinical presentation, and stage. The mean lesions size of ACC was higher in HVC than in LVC (104.1 +/- 54.6 vs 82.8 +/- 41.3 mm; P < 0.001). A significantly higher rate of lymph node dissection (P < 0.01) and of multiorgan resection (P < 0.01) was accomplished in HVC. The number of patients who underwent adjuvant therapy was significantly higher in HVC (P < 0.001). Local recurrence rate was lower in patients treated at HVC (6% vs 18.5%; P = NS). Mean time to recurrence was significantly longer in HVC than in LVC (25.2 +/- 28.1 vs 10.1 +/- 7.5; P < 0.01). CONCLUSION: The expertise of dedicated centers had a positive impact on the outcome of patients with ACC, resulting in a lower recurrence rate and improved mean time to recurrence. The improved patient outcome could be related not only to the appropriateness of the surgical procedure, but also to a more adequate multidisciplinary approach. PMID- 22069044 TI - Baroreceptor reflex dysfunction in the BACHD mouse model of Huntington's disease. AB - Huntington's disease is a progressive, neurodegenerative disorder that presents with a triad of clinical symptoms, which include movement abnormalities, emotional disturbance and cognitive impairment. Recent studies reported dysfunction of the autonomic nervous system in Huntington's disease patients, which may contribute to the increased incidence of cardiovascular events in this patient population that often leads to death. We measured the baroreceptor reflex, a process dependent on proper autonomic function, in the BACHD mouse model of Huntington's disease. We found a blunted response of the baroreceptor reflex as well as significantly higher daytime blood pressure in BACHD mice compared to WT controls, which are both indications of autonomic dysfunction. BACHD mice had increased heart weight to tibia length ratios at 7 and 12 mo of age suggesting hypertrophic changes of the heart, which we speculate is a response to the increased blood pressure and aberrant baroreceptor reflex. Despite these structural changes, the hearts of BACHD mice continue to function normally as assessed by echocardiographic analysis. Studies of autonomic and cardiovascular function in BACHD mice may help elucidate the pathophysiology of Huntington's disease and aid in the development of clinical strategies to offset the incidence of fatal cardiovascular events in the Huntington's disease patient population. PMID- 22069045 TI - Quantification of HBsAg and HBV-DNA during therapy with peginterferon alpha-2b plus lamivudine and peginterferon alpha-2b alone in a German chronic hepatitis B cohort. AB - BACKGROUND: Peginterferon alpha-2b (PEG-IFNa2b) and lamivudine are efficient treatment options for chronic hepatitis B virus (HBV) infection. We assumed that a combination therapy of PEG-IFNalpha-2b plus lamivudine will be more effective than PEG-IFNalpha-2b alone concerning loss of HBV-DNA, HBeAg seroconversion, and HBsAg reduction. PATIENTS AND METHODS: Patients with chronic hepatitis B were randomised to nine months treatment with PEG-IFNalpha-2b 1.5 ug/kg o. i. w. or PEG- IFNalpha-2b plus lamivudine 100 mg/d. The study was designed with 60 patients per treatment arm. The primary endpoint was defined as loss of HBV-DNA (< 400 copies/mL) 24 weeks after the end of therapy. HBV-DNA (PCR), HBsAg (Architect, Abbott), and HBeAg (Axsym, Abbott) were determined prior to and at the end of treatment as well as at follow-up. HBV-genotypes were determined by Innolipa (Innogenetics). RESULTS: Only 32 patients were randomised to combination therapy and 27 individuals to monotherapy due to low recruitment rates. On treatment reduction of HBV-DNA was significantly higher during combination therapy compared to PEG-IFNa-2b monotherapy (- 4.60 +/- 2.71 vs. - 2.41 +/- 2.17 log; p = 0.003). However, there was no difference in the number of cases achieving HBV-DNA < 400 copies/mL, ALT normalisation, or HBeAg seroconversion at follow-up. None of the parameters was significantly related to HBV-genotypes. In a post-hoc analysis serum HBsAg levels were analysed as an additional prognostic parameter for treatment response (n = 29). Combination therapy showed a stronger, but not significant HBsAg decline during (- 0.7 +/- 1.17 log IU/mL vs. - 0.26 +/- 0.61 log IU/mL; p = 0.35) and after therapy (- 0.68 +/- 1.29 log IU/mL vs. - 0.24 +/- 0.56 log IU/mL; p = 0.82). Two of three cases with a 2-log HBsAg decline to HBsAg levels < 100 IU/mL eliminated HBsAg during long-term follow-up. CONCLUSION: The study was underpowered with respect to the primary endpoint due to low recruitment rates. However, in the post-hoc analysis HBsAg decline was over two fold stronger at the end of treatment and follow-up after combination therapy and did not rebound after lamivudine withdrawal. These results may indicate the usefulness of future combination therapies without discontinuation of nucleos(t)ide analogues. PMID- 22069046 TI - [Extensive squamous papillomatosis of the oesophagus with malignant transformation of squamous epithelium]. AB - While small solitary oesophageal papillomas are uncommon findings that are occasionally identified on routine upper endoscopies, extensive oesophageal papillomatosis is an extremely rare condition with only 9 cases reported in the English literature. We report the case of a 72-year-old woman who was referred for progressive dysphagia for solid food and clinical signs for a reflux disease. Upper endoscopy demonstrated bizarre villous alterations of the mucosa covering the oesophagus subtotally and a suspicious area within these alterations. Histological work-up of the biopsy samples revealed marked papillary hypertrophy and a squamous epithelial carcinoma in situ corresponding to the suspicious lesion. The patient underwent oesophagectomy with cervical gastroesophageal anastomosis and proximal remnants of papillomatous mucosa above the anastomosis were destroyed with endoscopic argon plasma coagulation. In the 2-year follow-up the patient showed limited recurrence of the papillomatosis in the remaining proximal oesophagus containing a circumscript carcinoma that was successfully treated by local endoscopic mucosectomy. Our case strongly underscores the risk of malignant transformation in large areas of papillomatous mucosa and shows that systematic surveillance is essential. PMID- 22069047 TI - Hyperemesis and a high water bill. AB - A male patient aged 28 years was admitted with hyperemesis that did not cease in spite of different therapeutic approaches and had persisted for several days. A wide range of differential diagnoses was excluded and all tests remained without pathological findings. He reported regular cannabis use and showed abnormal bathing behavior taking hot showers several times a day for more than one hour each, which was the only measure to ease his nausea; on the basis of these clinical findings, the diagnosis of cannabinoid hyperemesis syndrome was made. After detoxification, he remained free of symptoms. Cannabinoid hyperemesis syndrome was first described in 2004 in Australia and is an underrecognized cause of hyperemesis and abnormal bathing behavior. To the best of our knowledge, this is the first reported case in Germany. PMID- 22069048 TI - [The enteric glia--part of the puzzle in Crohn's disease?]. AB - Enteric glia cells are essential for the mucosal integrity of the gut. A leakage of the epithelial barrier is postulated in Crohn's disease. The role of enteric glia cells in the onset and progress of Crohn's disease is not clear yet. A new approach in the therapy of Crohn's disease is to target "mucosal healing". Since enteric glia cells are an important source of factors that regulate the epithelial barrier function, further research and discussion about this cell entity under therapeutic aspects is urgently necessary. PMID- 22069049 TI - [High-protein reduced-carbohydrate weight-loss diets: negative impact on colonic health]. PMID- 22069050 TI - [Improved survival in patients with NET of the pancreas with molecular therapies]. PMID- 22069051 TI - [Walter Krienitz and one of the first descriptions of gastric bacteria]. PMID- 22069052 TI - [Recommendations for antibiotic prophylaxis in gastrointestinal endoscopy]. PMID- 22069053 TI - The observation of gaseous gold superions induced from monodispersed nanoparticles. PMID- 22069054 TI - p38 Mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland. AB - The lacrimal gland (LG) is an exocrine gland important for secretion of the tear film. The kinase p38 has important signal transduction functions, e.g. in gene transcription, but has previously not been known to modulate exocrine secretion. The aim of the current study was to investigate the role of p38 in carbachol (Cch)-induced LG secretion in LG acinar cells in vitro. Western blotting was used to determine the phosphorylation status of p38 and p42/44 and determine expression of p38 isoforms. To determine the effect of p38 inhibition on LG secretion, PD 169316, a general p38 inhibitor, and SB 239063, an inhibitor of p38alpha and beta, were added to the cells prior to secretion measurements. The results revealed activation of p38 mediated by Cch stimulation and inhibition of Cch-induced secretion as a result of p38 inhibition. The inhibition was observed with PD 169316 isoforms, but not with SB 239063. The p38delta isoform was shown to have robust expression both by Western blotting of acinar cells and immunofluorescence of the whole gland. In conclusion, p38 activation mediates secretion in cholinergic stimulation of rabbit LG cells. PMID- 22069055 TI - Three-dimensional closed microfluidic channel fabrication by stepper projection single step lithography: the diabolo effect. AB - Microfluidic devices are currently being used in many types of biochemical microsystems for liquid phase analysis in the frame of medical applications. This paper presents a new technique for the realization of microfluidic channels using SU-8, a commonly used epoxy-based negative photo-resist. These microchannels were fabricated by a single stepper UV-photolithography process. By changing the process parameters, e.g. the optical focus depth and the UV exposure dose, well defined, covered microchannels with various dimensions and aspect ratios were realized and proven to be effective for the fluid transport by capillarity. This technique can easily be used for the fabrication of microfluidic devices in the microanalysis and lab-on-chip applications realm. PMID- 22069056 TI - Overhauser DNP with 15N labelled Fremy's salt at 0.35 Tesla. AB - The effectiveness of dynamic nuclear polarization (DNP) as a tool to enhance the sensitivity of liquid state NMR critically depends on the choice of the optimal polarizer molecule. In this study the performance of (15)N labelled Fremy's salt as a polarizing agent in Overhauser DNP is investigated in detail at X-band (0.35 T, 9.7 GHz EPR, 15 MHz (1)H NMR) and compared to that of TEMPONE-D,(15)N employed in previous studies. Both radicals provide similar maximum enhancements of the solvent water protons under similar conditions but a different saturation behaviour. The factors determining the enhancement and effective saturation were measured independently by EPR, ELDOR and NMRD and are shown to fulfil the Overhauser equation. In particular, following the theory of EPR saturation we provide analytical solutions for the dependence of the enhancement on the microwave field strength in terms of saturation transfer between two coupled hyperfine lines undergoing spin exchange. The negative charge of the radical in Fremy's salt solutions can explain the peculiar properties of this polarizing agent and indicates different suitable application areas for the two types of nitroxide radicals. PMID- 22069057 TI - Psychological and social characteristics associated with religiosity in Women's Health Initiative participants. AB - Measures of religiosity are linked to health outcomes, possibly indicating mediating effects of associated psychological and social factors. We examined cross-sectional data from 92,539 postmenopausal participants of the Women's Health Initiative Observational Study who responded to questions on religious service attendance, psychological characteristics, and social support domains. We present odds ratios from multiple logistic regressions controlling for covariates. Women attending services weekly during the past month, compared with those not attending at all in the past month, were less likely to be depressed [OR = 0.78; CI = 0.74-0.83] or characterized by cynical hostility [OR = 0.94; CI = 0.90-0.98], and more likely to be optimistic [OR = 1.22; CI = 1.17-1.26]. They were also more likely to report overall positive social support [OR = 1.28; CI = 1.24-1.33], as well as social support of four subtypes (emotional/informational support, affection support, tangible support, and positive social interaction), and were less likely to report social strain [OR = 0.91; CI = 0.88-0.94]. However, those attending more or less than weekly were not less likely to be characterized by cynical hostility, nor were they less likely to report social strain, compared to those not attending during the past month. PMID- 22069058 TI - Maxillary osteonecrosis and spontaneous teeth exfoliation following herpes zoster. AB - BACKGROUND: Reports of osteonecrosis and spontaneous tooth loss following herpes zoster infection of the fifth cranial are extremely rare. Only 39 previously recorded cases of post-zoster osteonecrosis have been found in the literature. The unusual feature of the case of interest to the dental surgeon is a rare complication of tooth exfoliation and maxillary osteonecrosis. CASE REPORT: This article reports a case of 52-year-old man with herpes zoster infection of the trigeminal nerve and related alveolar bone necrosis and teeth loss. The etiology and management of herpes zoster infection associated with destructive sequelae are discussed. DISCUSSION: Very few cases of osteonecrosis and spontaneous teeth exfoliation secondary to herpes zoster are found in the literature. The exact mechanism by which herpes zoster induces these destructive changes in the alveolar bone and teeth cannot be proposed. As Varicella zoster virus is an aneurotropic virus, the possible provoking factors may be the infection of the nerves innervating the periosteum or the chronic inflammatory changes in the form of adverse periodontal disease and delayed healing of the extraction sockets associated with compromised host resistance. PMID- 22069060 TI - Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab is associated with a profound long-lasting depletion of Foxp3+ regulatory T cells: a mechanistic explanation for ipilimumab-induced severe enterocolitis? PMID- 22069059 TI - Small bite, large impact-saliva and salivary molecules in the medicinal leech, Hirudo medicinalis. AB - Blood-sucking leeches have been used for medical purposes in humans for hundreds of years. Accordingly, one of the most prominent species has been named Hirudo medicinalis by Carl Linne in 1758. Feeding on vertebrate blood poses some serious problems to blood-sucking ectoparasites, as they have to penetrate the body surface of the host and to suppress the normal reactions of the host to such injuries (swelling, pain, inflammation) to remain undetected during the feeding period. Furthermore, the parasites have to take measures to inhibit the normal reactions in host tissues to blood vessel damage, namely hemostasis and blood coagulation (platelet aggregation and activation, activation of thrombin and formation of fibrin clots). During evolution, leeches have acquired the ability to control these processes in their hosts by transferring various bioactive substances to the host. These substances are supposedly produced in unicellular salivary gland cells and injected into the wound at the feeding site through tiny salivary ductule openings in the jaws that the leech uses to slice open the host body surface and to cut blood vessels in the depth of the wound. This review summarizes current knowledge about the salivary gland cells and the biological effects of individual saliva components as well as hints to the potential usefulness of some of these compounds for medical purposes. PMID- 22069061 TI - Predictors of early cessation of dairy farming in the French Doubs province: 12 year follow-up. AB - BACKGROUND: A healthy worker effect due to respiratory disability has been noted in the farming population, but other factors may also interfere. Little has been published about factors influencing the early cessation of work in self-employed dairy farmers. METHODS: Two hundred and nineteen dairy farmers were included from a cohort constituted in eastern France in 1993-1994 with a 12-year follow-up. Spirometric data, personal, and farm characteristics were registered. Cox models with delayed entry in which age was the time-scale were applied to identify the baseline predictive factors of the early cessation of dairy farming. RESULTS: Working in a modern farm was protective against early cessation of dairy farming (hazard ratio: 0.36 [95% CI: 0.16-0.81]), especially in men. Having asthma was a predictive factor of early cessation, especially in women (hazard ratio: 16.12 [95% CI: 3.28-79.12]). CONCLUSIONS: The most predictive factors of early cessation of dairy farming were health related in women and farm related in men. PMID- 22069062 TI - Fat grafting versus adipose-derived stem cell therapy: distinguishing indications, techniques, and outcomes. AB - With adipose-derived stem cells (ASCs) at the forefront of research and potential clinical applications, it is important that clinicians be able to distinguish them from the fat grafting currently used clinically and to understand how the two approaches relate to one another. At times, there has been confusion in clinically considering the two therapies to be the same. This report is aimed at distinguishing clearly between fat grafting and ASC therapy with regard to the indications, harvesting, processing, application techniques, outcomes, and complications. Findings have shown that autologous fat transfer, a widely used procedure for soft tissue augmentation, is beneficial for reconstructive and cosmetic procedures used to treat patients with volume loss due to disease, trauma, congenital defects, or the natural process of aging. On the other hand, ASCs have been identified as an ideal source of cells for regenerative medicine, with the potential to serve as soft tissue therapy for irradiated, scarred, or chronic wounds. Recent advances in tissue engineering suggest that the supplementation of fat grafts with ASCs isolated in the stromal vascular fraction may increase the longevity and quality of the fat graft. Research suggests that ASC supplementation may be a great clinical tool in the future, but more data should be acquired before clinical applications. PMID- 22069064 TI - [Prevention of vertical HIV-1 transmission in a tertiary care public hospital in Buenos Aires, Argentina]. AB - OBJECTIVE: To describe characteristics of mother-child binomium (MCB), antiretroviral (ARV) prophylaxis, time trends, and variables associated with vertical transmission of HIV-1 in a population assisted by a tertiary public hospital in Argentina. METHODS: Prospective descriptive study undertaken by the Hospital Cosme Argerich s Vertical Transmission Working Group, Buenos Aires city, Argentina 1998-2008. Periods 1998-2003 vs. 2004-2008 were compared and variables associated with vertical transmission identified. RESULTS: Of 357 MCB, 21.0% of the mothers had HCV coinfection and 68.0% CD4 < 500/uL. During pregnancy, 75.0% received ARV: zidovudine (17.8%), zidovudinelamivudine (19.8%), zidovudine lamivudine-nevirapine (41.9%), and zidovudinelamivudine-protease inhibitor (11.4%); 74.0% had viral load (VL) peripartum < 1 000 copies/mL. Caesarean delivery: 58.0%. Intrapartum zidovudine: 83.4%; 98.0% of infants received prophylaxis; zidovudine monotherapy was the most frequently used (73.0%). Of neonates, 15.4% had low birthweight and 6.7% were premature. The global vertical transmission was 3.3% (10/302). Comparing both periods, an increase in triple ARV and VL < 1 000 copies/mL in peripartum and a decrease in the absence of maternal/neonatal prophylaxis and overall VT was observed. The vertical transmission for 2004-2008 was 1.3% vs. 6.3% in Buenos Aires city (official statistics). Absence of maternal/intrapartum prophylaxis and prematurity were associated with vertical transmission (P < 0.01 and P = 0.01, respectively). CONCLUSIONS: A decline in overall vertical transmission between the two periods was observed attributable to increased coverage of maternal/neonatal ARV administration and increased use of triple therapy. The absence of maternal/intrapartum prophylaxis was the main factor associated with vertical transmission, emphasizing the need to improve accessibility of MCB to the local public health system. PMID- 22069065 TI - Intervention to prevent intestinal parasitic reinfections among Tarahumara indigenous schoolchildren in northern Mexico. AB - OBJECTIVE: To assess the effectiveness of a 20-week, broad intervention to prevent reinfection by Ascaris lumbricoides (AL) and Giardia lamblia (GL) among indigenous schoolchildren in northern Mexico. METHODS: A prospective, comparative, ecological study. Two isolated boarding schools, each hosting 100 120 children, 4-15 years of age, were selected based on physical infrastructure: intervention school (IS), modern; control school (CS), deprived. After initial diagnosis, children with positive stool samples received supervised treatment with oral nitazoxanide. Diagnoses were made with at least one positive microscopic result from two serial samples using the Faust technique, as reported by the independent observations of two trained, laboratory technicians. Post treatment samples were taken, and only those with negative results were followed up. The intervention included infrastructure improvements/maintenance and an educational preventive program for children, parents, and school personnel; no activities were undertaken in the CS. RESULTS: Baseline prevalence for AL was 37.5% at the IS versus 16.6% at the CS (P < 0.01); and for GL, 51.7% versus 37.8%, respectively. At the IS, 35.7% did not speak Spanish, compared to 6.7% in the CS (P < 0.01). Cure rates were similar in both schools for AL (~ 98%) and GL (~ 80%). Final prevalence and reinfection rates for GL were 10.4% versus 10.8%, and 17.2% versus 21% at the IS and CS, respectively. No children were infected/reinfected with AL in either school. Follow-up rates were 80%-83% at the CS and 90%-95% at the IS. CONCLUSIONS: Infection/reinfection rates were similar at the schools after 20 weeks. Supervised treatment alone every semester could effectively control AL/GL infections in this indigenous setting. PMID- 22069066 TI - [Perception of patients with chronic hemiplegia regarding the use of assistive walking devices]. AB - OBJECTIVE: To assess the perception of patients with chronic hemiplegia regarding the use of assistive walking devices (AWD). METHODS: Twenty-three individuals who met the inclusion criteria and used AWD were recruited from a database of 360 stroke survivors. Their mean age was 58.4 years, mean time since stroke was 80.8 months, and mean time using AWD was 67.6 months. To assess the participants' perception, was used a standardized questionnaire covering the impact of AWDs on five aspects: weight-bearing on the paretic limb; ability to move the paretic limb; confidence; safety; and walking style. Possible answers were "improved," "unchanged," or "decreased." RESULTS: Fourteen individuals used canes and nine used elbow crutches; 21 (91.3%) used AWDs on public roads and only two (8.7%) used AWDs at home. The perception regarding the use of AWDs were positive in the first four questions (6.87 < chi2 < 29.83; 0.0001 < P < 0.03), with reports of improvement in weight-bearing (82.6%), ability to move the paretic limb (39.1%), confidence (82.6%), and safety (86.9%). No significant differences were found in terms of walking style (chi2 = 1.09; P = 0.30). CONCLUSIONS: The perception of chronic hemiplegic subjects regarding the use of AWD were positive, suggesting that these devices can improve mobility and independence in activities of daily living. PMID- 22069063 TI - Silencing disease genes in the laboratory and the clinic. AB - Synthetic nucleic acids are commonly used laboratory tools for modulating gene expression and have the potential to be widely used in the clinic. Progress towards nucleic acid drugs, however, has been slow and many challenges remain to be overcome before their full impact on patient care can be understood. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression. We first describe these two approaches and contrast their relative strengths and weaknesses for laboratory applications. We then review the choices faced during development of clinical candidates and the current state of clinical trials. Attitudes towards clinical development of nucleic acid silencing strategies have repeatedly swung from optimism to depression during the past 20 years. Our goal is to provide the information needed to design robust studies with oligonucleotides, making use of the strengths of each oligonucleotide technology. PMID- 22069067 TI - [Epidemiological and economic impact of tetanus vaccination in Colombian adults]. AB - OBJECTIVE: Assess the potential epidemiological and economic impact of vaccinating the over-15 Colombian population against tetanus with a booster dose every 10 years. METHODS: A cost-effectiveness analysis of tetanus vaccination with a booster dose every 10 years was conducted in Colombia and compared with the current strategy (2, 4, 6, 18, and 60 months). Estimates of the burden of disease were based on three official data sources. A Markov model from the perspective of the third party payer was developed. The time horizon was the lifetime of a person. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In Colombia, 30 to 48 cases of tetanus resulting in 9.6 to 10.1 deaths are reported each year. Although booster vaccination for the entire population was cost-effective (the cost per disability-adjusted life year [DALY] avoided was US$ 11,314 in the entire population), gender-based differentiation of the results showed that it would not be cost-effective in women (cost per DALY avoided was US$ 4,903 in men and US$ 22,332 in women). CONCLUSIONS: This is the first study that evaluates the cost-effectiveness of a tetanus vaccine booster dose every 10 years in a developing country. Use of this measure would be cost effective in Colombia, especially for men. As a result of the gender-based differences in the results, any decision about its use in women of childbearing age should take current vaccination into account. PMID- 22069068 TI - Implementation and progress of an inclusive primary health care model in Guatemala: coverage, quality, and utilization. AB - OBJECTIVE: To describe a primary health care model designed specifically for Guatemala that has been implemented in two demonstration sites since 2004 and present results of a process evaluation of utilization, service coverage, and quality of care from 2005 to 2009. METHODS: Coverage, utilization, and quality were assessed by using an automated database linking census and clinical records and were reported over time. Key maternal and child health coverage measures were compared with national-level measures. RESULTS: The postnatal coverage achieved by the Modelo Incluyente de Salud of nearly 100.0% at both sites contrasts with the national average of 25.6%. Vaccination coverage for children aged 12-23 months in the Modelo Incluyente de Salud reached 95.6% at site 1 (Bocacosta, Solola) and 92.7% at site 2 (San Juan Ostuncalco), compared with the national average of 71.2%. Adherence to national treatment guidelines increased significantly at both sites with a marked increase between 2006 and 2007. Utilization increased significantly at both sites, with only 7.5% of families at site 1 and 11.2% of families at site 2 not using services by the end of the 5 year period. CONCLUSIONS: Coverage, quality of care, and utilization measures increased significantly during the 5-year period when the service delivery model was implemented. This finding suggests a strong possibility that the model may have a benefit for health outcomes as well as for process measures. The Modelo Incluyente de Salud will be financially sustained by the Ministry of Health and extended to at least three additional sites. The model provides important lessons for primary care programs internationally. PMID- 22069069 TI - [Application of the intrinsic estimator to breast cancer mortality rates]. AB - OBJECTIVE: Assess use of the intrinsic estimator (IE) technique in epidemiology. METHODS: The IE approach was applied to the analysis of breast cancer data in Argentina in order to observe the trends associated with "age, period, and cohort" (APC). This method involves the use of a principal components regression to obtain a single set of estimated trends. The results were compared to the findings obtained with the conventional method, which consists of adjusting a generalized linear model that includes the traditional constraints of the statistical model as well as an additional constraint (CGLM). RESULTS: Both methods yielded compatible results in the trends associated with APC. However, they differed in the confidence intervals, with IE yielding greater efficiency. The curve associated with age showed the expected pattern of change across the life course: the greater the age, the greater the risk. With regard to cohorts, a decrease in the effects associated with the most recent cohorts was evident, whereas there was very little variation in the estimated effects for the period. CONCLUSIONS: A comparison of the results obtained with the IE method and the CGLM method revealed the reach of the generic solution provided by the IE to the problem of estimates in an APC model. The IE method is based on conversion of the data observed using a weighting matrix that is simple to apply and provides estimates with desirable statistical properties. PMID- 22069070 TI - [Assessment of the impact of the NGO Refazer on medical care for children at social risk]. AB - OBJECTIVE: Assess the impact of activities by the nongovernmental organization Refazer in support of medical care for children at social risk. METHODS: A longitudinal study was conducted of 77 patients from Rio de Janeiro in treatment at the Fernandes Figueira Institute and supported by Refazer. The assessment period was two years, one before and the other during the intervention period while being supported by the NGO. The percentage of hospitalizations, average length of stay, severity of the illness, use of technology, number of outpatient consultations, and clinical conditions involved were compared. RESULTS: The indicators linked with the hospitalizations revealed changes during the intervention period. There was a reduction in the average time and percentage of hospitalization. The most common pathologies were congenital malformations, chromosomal anomalies, and diseases of the nervous system. These diseases and HIV/AIDS were more prevalent in children that remained hospitalized even after receiving support from the NGO. CONCLUSIONS: Analysis of the indicators showed that the outcomes are adequate to the NGO's mission and that the population helped benefits from participation in the social support network. Although it cannot be stated that the benefits found are due exclusively to the activities of the NGO, a simple and easy-to-use evaluation of adequacy was developed that NGOs themselves can use, representing progress toward the institutional use of evaluations by NGOs working in health. PMID- 22069071 TI - Patterns and predictors of current cigarette smoking in women and men of reproductive age-Ecuador, El Salvador, Guatemala, and Honduras. AB - OBJECTIVE: To estimate smoking prevalence by gender, describe patterns of cigarette use, and identify predictors of current smoking in reproductive-age adults in four Latin American countries. METHODS: Self-reported smoking was examined using data from Reproductive Health Surveys of women aged 15-49 years in Ecuador (2004), El Salvador (2002-2003), Guatemala (2002), and Honduras (2001), and of men aged 15-59 years in El Salvador, Guatemala, and Honduras for the same years. Current smoking was assessed by demographic characteristics, and independent associations were examined using logistic regression. Data were weighted to be nationally representative of households with reproductive-age women and men. RESULTS: Current smoking prevalence ranged from 2.6% (Guatemala) to 13.1% (Ecuador) for women and from 23.1% (Guatemala) to 34.9% (El Salvador) for men. In Ecuador, 67.6% of female smokers were non-daily users; in other countries, daily use was more prevalent than non-daily use for both men and women. In daily users, the median number of cigarettes smoked per day ranged from 1.9 (Ecuador, Honduras) to 2.3 (Guatemala) for women and from 2.1 (Guatemala) to 3.6 (Honduras) for men. In bivariate analysis, smoking prevalence in all countries was highest in women who lived in urban areas, were previously married, and/or had high socioeconomic status. Risk factors for smoking varied by country and gender. CONCLUSIONS: National tobacco control programs in these countries should aggressively target high-risk populations (reproductive-age men) and maintain low prevalence in low-risk populations (reproductive-age women). More research is needed to understand addiction patterns in non-daily smokers. PMID- 22069072 TI - [Reducing hospitalization with the use of a dengue management algorithm in Colombia]. AB - OBJECTIVE: Assess the impact of a dengue management algorithm on the hospitalization rate of patients with suspected disease in a primary care health facility in an endemic area of Colombia. METHODS: A quasi-experimental study was conducted at the local hospital in Piedecuesta, Santander, Colombia, based on comparison of two periods (18 weeks each), before and after use of the algorithm. This included recommendations for clinical diagnosis of dengue and the planning of follow-up visits and hemograms, as well as criteria for hospitalization and the discontinuation of follow-up. Hospitalization rates in the two periods were compared using the Poisson analysis. The population analyzed consisted of patients seen in the facility for acute febrile syndrome. For adjustment purposes, the number of dengue cases (IgM positive) identified in the municipality was included. RESULTS: Information was obtained on 964 patients in the first period and 1350 patients in the second. There were 44 and 13 hospitalizations during the respective periods. Use of the algorithm was associated with a significant reduction in the hospitalization rate (ratio: 0.21; 95% confidence interval; 0.11-0.39). This association did not change when adjusted for the number of dengue cases identified in the city. There were no significant differences in the rate of follow-up visits (P = 0.85) and hemograms (P = 0.24) in the two periods. There were no case fatalities. CONCLUSIONS: The results suggest that health care resources for dengue management can be optimized with the use of the algorithm. PMID- 22069073 TI - Redefining personality disorder: a Jamaican perspective. AB - OBJECTIVE: To characterize and assess the factor structure of phenomenological features of DSM-IV personality disorder diagnosis in Jamaican patients and determine any similarities with those of traditional criteria, associations with disorder severity, and/or significant relationships between variables to inform the current debate on the relevance of established personality disorder diagnostics. METHODS: This was a case-control study. All the patients included were seen by one private psychiatric practice from 1974 to 2007. The study sample group (n = 351) were patients diagnosed as having a personality disorder (DSM-IV Axis II). The control group was composed of patients with DSM-IV Axis I clinical disorders, who had not been diagnosed with a personality disorder, and matched exactly on gender, and closely on age, as well as socioeconomic variables. RESULTS: Of the 351 individuals in the study sample group, 166 (47.3%) were male and 185 (53.7%) were female; 50 (14.2%) were white and 301 (85.8%) were black; 293 (83.5%) were born and raised in Jamaica; and 202 (57.6%) were from socioeconomic classes I and II. Mean age was 33.92 (standard deviation 10.236). Disaggregating the phenomenology, the conventional DSM-IV personality disorder diagnoses disappeared. Factor analysis of 38 clinical phenomena identified five components: psychosis, major depression, power management problems, psychosexual issues, and physiological dependency. Independent t-tests revealed patients without personality disorder had significantly higher mean scores for psychosis; both groups scored equally for depression; and those with personality disorder had significantly higher mean scores on the remaining factors. Analysis of variance indicated these factors differed significantly for three levels of severity (mild, moderate, and severe). CONCLUSIONS: The phenomenology clustering into three major groups suggested an Axis I (clinical) diagnostic disorder of impulse control and authority and conflict management. PMID- 22069074 TI - [Cross-cultural adaptation and analysis of the psychometric properties of the Brazilian version of the Motor Activity Log]. AB - OBJECTIVE: To describe the translation into Brazilian Portuguese and cross cultural adaptation of the Motor Activity Log (MAL), an instrument specifically designed to assess function of the more severely affected upper limb in hemiplegics. METHODS: The MAL was translated and adapted according to standardized procedures and submitted to test-retest reliability assessment (intraclass correlation coefficient, ICC). Other psychometric properties were investigated using Rasch analysis in 77 chronic hemiplegics (41 men, mean age = 57.5 +/- 12.4 years). RESULTS: An excellent ICC (0.98) was obtained for the total scores of both the quantity and quality MAL scales. When assessing degree of difficulty, "using a key to unlock the door" was the most difficult item on the quantity scale, whereas "washing hands" was the easiest one. On the quality scale, the most difficult item was "using the TV remote control," and the easiest one was "drying hands." The analyses showed that the set of items as a whole fit into the model; however, the individual analyses indicated that four items did not meet the expectations of the model in both the quantity (items 21, 16, 14, and 13) and quality (items 9, 21, 23, and 22) scales. Irregular response patterns were observed, and five subjects obtained the minimum score. There was disagreement between item difficulty and sample ability, suggesting that the abilities of individuals were below the degree of difficulty of the assessed items. A significant correlation was observed between grip strength of the more severely affected upper limb and motor skill measurement among individuals on the quantity (r = 0.51, P < 0.0001) and quality scales (r = 0.57, P < 0.0001), and also between the two scales when measuring the individuals' motor skills (r = 0.97, P < 0.0001). CONCLUSIONS: MAL-Brazil is potentially useful to evaluate the more severely affected upper limb in Brazilian patients with chronic hemiplegia. However, the instrument has limitations for use with individuals with severe limb impairments. Also, construct validity was affected by the presence of irregular score patterns. MAL-Brazil should be applied to additional samples to further investigate its validity. PMID- 22069076 TI - Situation of bovine tuberculosis in Ecuador. AB - Bovine tuberculosis (BTB) is a chronic and contagious disease that affects domestic animals, wildlife, and humans. Caused by Mycobacterium bovis, BTB causes major economic losses and poses a serious constraint to international livestock trade. Moreover, in developing countries where BTB controls are lacking, M. bovis is a public health concern. In most developing countries, the prevalence of BTB in livestock is unknown because the information is either not reported or not available. In Ecuador, there is no national BTB control program. This article reviews the BTB situation in Ecuador by examining exhaustive data from tuberculin testing surveys and slaughterhouse surveillance studies conducted in 1972-2008 in a variety of the country's geographic areas. In Ecuador, several factors, including the dairy industry's expansion (preempted by the high demand for milk and its by-products), intensified efforts to increase the cattle population, the presence of M. bovis, and a lack of BTB controls, have caused a rise in BTB prevalence, and consequently, a growing push for the implementation of a national BTB control program. PMID- 22069075 TI - [A health care model for the Wayuu people on the Colombian-Venezuelan border]. AB - At meetings and workshops with Wayuu communities and government officials from Colombia and Venezuela, after validating the analysis of the health situation and its determinants, the components of a binational health care model for the Wayuu people living on the border between the two countries were identified. Although both countries have made progress in intercultural health care, some aspects of their legislation and service organization still need to be strengthened to make the guaranteed right to health a reality. The allocation of new national resources-or the redistribution of current resources-should be ensured, as well as the management of international resources for conducting a short-term pilot project and implementing the model in the medium term. PMID- 22069077 TI - Comparison of Comet assay dose-response for ethyl methanesulfonate using freshly prepared versus cryopreserved tissues. AB - The National Toxicology Program (NTP) is using the Comet assay to evaluate genotoxic potential, and is investigating the integration of this assay into repeat-dose toxicity studies. To reduce sample-to-sample variability, address logistical concerns associated with evaluating multiple tissues from many animals, and accommodate sample collection at geographically distant testing facilities, tissue samples collected for Comet analysis by the NTP are routinely flash-frozen in liquid nitrogen and stored in a -80 degrees C freezer until evaluation. To compare data obtained from frozen tissues to data from freshly isolated tissues, we conducted a dose-response study in male Sprague Dawley rats. Rats (5 per treatment group) were administered ethyl methanesulfonate (EMS; 0, 25, 50, 100, or 200 mg/kg) by gavage twice at an interval of 21 hr; blood, liver, stomach, and colon tissues were harvested 3 hr after the second treatment. Single cell preparations from each of the four tissues were put into Hank's balanced salt solution with 10% fresh dimethyl sulfoxide. One aliquot of each tissue preparation was used for immediate analysis, while additional aliquots were flash frozen in liquid nitrogen and stored in a -80 degrees C freezer for 1 or 8 weeks. One set of 8-week frozen samples was shipped roundtrip via air courier from Research Triangle Park, NC to Rochester, NY prior to analysis. For all four tissues, results from frozen, nontransported samples showed a similar dose response pattern for EMS-induced genotoxicity. We also demonstrated that for three tissues (blood, liver, stomach), air transport did not alter the sensitivity of the Comet assay for detecting DNA damage. PMID- 22069078 TI - Modulatory effects of acupuncture on resting-state networks: a functional MRI study combining independent component analysis and multivariate Granger causality analysis. AB - PURPOSE: To investigate acupuncture specificity by exploring causal relationships of brain networks following acupuncture at GB40 (Qiuxu), with the acupoint KI3 (Taixi) as a control (belonging to the same nerve segment but different meridians). MATERIALS AND METHODS: Needling at acupoints GB40 and KI3 was performed in 12 subjects separately. The specific coherent patterns, resting state networks (RSNs), were retrieved by independent component analysis (ICA) from functional magnetic resonance imaging (fMRI) data of resting state and post acupuncture resting states, respectively. Then multivariate Granger causality analysis (mGCA) was applied to evaluate the effective connectivity within and among the detected RSNs-default model, memory, executive, auditory, and motor brain networks. RESULTS: Following acupuncture at GB40, the strength of causal connectivity between the superior temporal gyrus (STG) and anterior insula was enhanced, while the connection strength between the STG and postcentral gyrus increased following acupuncture at KI3. Additionally, the causal influences within the auditory network increased following acupuncture at GB40, in comparison with the executive network following acupuncture at KI3. CONCLUSION: The current study demonstrates that acupuncture at different acupoints could exert different modulatory effects on RSNs. Our findings may help to understand the neurophysiological mechanisms underlying acupuncture specificity. PMID- 22069079 TI - Quantification of kinase activity in cell lysates via photopatterned macroporous poly(ethylene glycol) hydrogel arrays in microfluidic channels. AB - The efficacy of tyrosine kinase inhibitors (TKIs) as cancer therapeutics varies amongst individual patients as a result of patient-specific differences in molecular regulation of cancer development and progression, and acquisition of resistance to TKIs during therapy. A sensitive assay that can quantify kinase activity and predict inhibition of that activity from minimally invasive patient tissue samples may aid design of efficacious individualized TKI treatments. A microfluidic format can be useful in reducing limitations in standard protein kinase assays, including sensitivity required and low sample volume available. We present photopatterned macroporous poly(ethylene glycol) diacrylate hydrogel pillars functionalized with kinase substrates within microchannels for quantifying kinase activity in complex cellular lysates. We determined the effect of using a porogen to induce macroporosity in hydrogel pillars and showed that hydrogel poration enhanced the sensitivity of detecting Bcr-Abl activity in cell lysates by an order of magnitude. Bcr-Abl tyrosine kinase activity in K562 cell lysates could be detected from 0.01 MUg/MUL of cell lysate, corresponding to approximately 500 cells, using GST-Crkl immobilized in macroporous hydrogels. This device was also capable of quantifying inhibition of Bcr-Abl activity by imatinib mesylate, which demonstrates the potential to predict the biochemical response to drug inhibitors. These results indicate that microfluidic devices containing macroporous hydrogels functionalized with kinase substrates provide a promising platform for sensitive and specific quantification of kinase activity and efficacy of kinase inhibitors in cancer cell lysates. PMID- 22069080 TI - Microstructuring of multiwell plates for three-dimensional cell culture applications by ultrasonic embossing. AB - Since three-dimensional (3D) cell culture models better reflect tissues in vivo in terms of cell shape and microenvironment compared to conventional monolayer cultures, 3D tissue culture substrates gain more importance for a wide range of biological applications like drug discovery, toxicological studies, cancer and stem cell research. In this study we developed a method for the fabrication of 3D cell culture substrates in a multiwell plate format by microstructuring the bottom of 96-well cell culture plates using an ultrasonic embossing process. The resulting microstructured area consists of cubic microcavities in which adherent multicellular aggregates can be formed. We performed the biological evaluation of the system with the liver-derived human cell-line HepG2 and compared the novel substrate with a commercially available 3D culture system comprising porous alginate sponges. Metabolic activity (alamarBlue(r) reduction) and induction of four biotransformation enzymes (EROD, ECOD, UGT, SULT) were determined by fluorimetry or HPLC. Our results revealed that HepG2 cells in microstructured plates showed a higher mitochondrial activity, as well as enzyme activity of ECOD and UGT after treatment with an inducer when compared to cells cultured in alginate sponges at otherwise comparable conditions. Since we have modified standard cell culture plates, the obtained system is adaptable to automated screening and might be useful for all kinds of cultures including adult, progenitor and stem cells which need a 3D culture configuration to restore or maintain the differentiated status. PMID- 22069081 TI - Perception of the end position of a limb loaded with a weight. AB - We examined the effect of loading a weight on the perception of the end position of the limb. The participants haptically perceived where the end of their limb was located while they swung the limb or statically held it. The results showed that the loading of a weight influenced participants' perception only when they swung the limb; when the weight was attached to a participant's hand, the position was perceived to be farther from the body than when the weight was attached to the forearm or no weight was attached. We also found that the end position was generally underestimated when the participants swung their limb. On the other hand, when the participants statically held their limb, the perceived position was not affected by the loading of the weight and was rather precise. These results suggest that the perceptual system for limb end position is sensitive to changes in the surrounding haptic information caused by moving the limb. PMID- 22069083 TI - The impact of category separation on unsupervised categorization. AB - Most previous research on unsupervised categorization has used unconstrained tasks in which no instructions are provided about the underlying category structure or in which the stimuli are not clustered into categories. Few studies have investigated constrained tasks in which the goal is to learn predefined stimulus clusters in the absence of feedback. These studies have generally reported good performance when the stimulus clusters could be separated by a one dimensional rule. In the present study, we investigated the limits of this ability. Results suggest that even when two stimulus clusters are as widely separated, as in previous studies, performance is poor if within-category variance on the relevant dimension is nonnegligible. In fact, under these conditions, many participants failed even to identify the single relevant stimulus dimension. This poor performance is generally incompatible with all current models of unsupervised category learning. PMID- 22069082 TI - Curved apparent motion induced by amodal completion. AB - We investigated whether amodal completion can bias apparent motion (AM) to deviate from its default straight path toward a longer curved path, which would violate the well-established principle that AM follows the shortest possible path. Observers viewed motion sequences of two alternating rectangular tokens positioned at the ends of a semicircular occluder, with varying interstimulus intervals (ISIs; 100-500 ms). At short ISIs, observers tended to report simple straight-path motion-that is, outside the occluder. But at long ISIs, they became increasingly likely to report a curved-path motion behind the occluder. This tendency toward reporting curved-path motion was influenced by the shape of tokens, display orientation, the gap between tokens and the occluder, and binocular depth cues. Our results suggest that the visual system tends to minimize unexplained absence of a moving object, as well as its path length, such that AM deviates from the shortest path when amodal integration of motion trajectory behind the curved occluder can account for the objective invisibility of the object during the ISI. PMID- 22069084 TI - Productivity enhancement of C=C bioreductions by coupling the in situ substrate feeding product removal technology with isolated enzymes. AB - To overcome the usually low productivities of the C=C bond bioreduction of alpha,beta-unsaturated aldehydes we combined the in situ substrate feeding product removal (SFPR) technology with a cascade system comprising an isolated ene-reductase and a chemoselective alcohol dehydrogenase. PMID- 22069085 TI - Synthesis and in vitro enzymatic and antiviral evaluation of phosphoramidate d4T derivatives as chain terminators. AB - The anti-HIV activity of nucleoside analogues is highly related to their substrate specificity for cellular and viral kinase and, as triphosphate, for HIV RT. A series of phosphoramidate d4T derivatives have been synthesized and evaluated as substrates for HIV-1 RT, and also tested for their in vitro anti-HIV activity. Compounds 2 and 4 are able to inhibit HIV-1 replication to the same extent as d4T and d4TMP in MT-4 cells as well as in CEM/0 cells and CEM/TK(-) cells. The data suggests that these phosphoramidates are hydrolysed to d4T before exerting their antiviral activity. PMID- 22069086 TI - Dinuclear Rh(II) pyrazolates as CVD precursors for rhodium thin films. AB - New dinuclear rhodium(II) pyrazolate (Pz) complexes of formula Rh(2)(3-R,5 R'Pz)(4).2L (R = R' = CF(3), L = H(2)O (1), CH(3)CN (2)) and Rh(2)(3-R,5-R'Pz)(4) (R = R' = (t)Bu (3); R = CF(3), R' = (t)Bu (4)) have been synthesized from the interaction of the lithium salt of the corresponding pyrazole with Rh(2)(OAc)(4) in diethyl ether. The complexes were characterized by X-ray crystallography and spectroscopic methods. They were further evaluated as precursors for the chemical vapor deposition (CVD) of Rh thin films using H(2) as the carrier gas. The resulting films were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). PMID- 22069087 TI - Risk factors for elevated INR values during warfarin therapy in hospitalized pediatric patients. AB - BACKGROUND: There are currently no data describing the incidence of or risk factors for elevated International Normalized Ratio (INR) values in patients receiving warfarin at a tertiary care pediatric hospital. By minimizing risk factors for elevated INR values patient morbidity may be minimized. PROCEDURES: A 6-year retrospective chart review of inpatient admissions at our institution that received warfarin was performed. Factors for elevated INR values, such as patient demographics, disease state, and medication interactions were reviewed. Patients with an INR value >= 0.5 above the upper limit of the goal range were compared to patients without an elevated INR value. A logistic regression analysis was performed to identify independent variables for elevated INR values. RESULTS: A total of 298 patient admissions (184 patients) met study criteria, and the largest patient population was between 1 and 12 years old (36.9%). The most common indication for warfarin was mitral valve replacement (25.5%). An elevated INR occurred in 20.8% of admissions. Logistic regression analysis identified Asian race, an elevated baseline INR value, warfarin initiation after cardiac surgery, days of inpatient warfarin therapy, and drug interactions with ciprofloxacin and lansoprazole as independent variables for an elevated INR value (P < 0.05). Obesity was significant as an independent variable for a non-elevated INR value (P < 0.05). CONCLUSIONS: Elevated INR values occur often in patients receiving warfarin while admitted to a tertiary care pediatric facility and modifiable risk factors exist for elevated INR values. PMID- 22069089 TI - Editorial: Biotechnology Journal shines the spotlight on ACB-2011. PMID- 22069092 TI - Meeting report: ACB-2011 Shanghai - "biotechnology for better life". PMID- 22069094 TI - Cancer hyperthermia using magnetic nanoparticles. AB - Magnetic-nanoparticle-mediated intracellular hyperthermia has the potential to achieve localized tumor heating without any side effects. The technique consists of targeting magnetic nanoparticles to tumor tissue followed by application of an external alternating magnetic field that induces heat through Neel relaxation loss of the magnetic nanoparticles. The temperature in tumor tissue is increased to above 43 degrees C, which causes necrosis of cancer cells, but does not damage surrounding normal tissue. Among magnetic nanoparticles available, magnetite has been extensively studied. Recent years have seen remarkable advances in magnetite nanoparticle-mediated hyperthermia; both functional magnetite nanoparticles and alternating-magnetic-field generators have been developed. In addition to the expected tumor cell death, hyperthermia treatment has also induced unexpected biological responses, such as tumor-specific immune responses as a result of heat shock protein expression. These results suggest that hyperthermia is able to kill not only local tumors exposed to heat treatment, but also tumors at distant sites, including metastatic cancer cells. Currently, several research centers have begun clinical trials with promising results, suggesting that the time may have come for clinical applications. This review describes recent advances in magnetite nanoparticle-mediated hyperthermia. PMID- 22069095 TI - Evaluating (13)C enrichment data of free amino acids for precise metabolic flux analysis. AB - Metabolic flux analysis using (13)C enrichment data of intracellular free amino acids (FAAs) can improve the time resolution of flux estimation compared to analysis of proteinogenic amino acid data owing to the faster turnover times of FAAs. The nature of the (13)C enrichment dynamics of FAAs remains obscure, however, especially with regard to its dependence on culture conditions, even though an understanding of dynamic behavior is important for precise metabolic flux estimation. In this study, we analyzed the (13)C enrichment dynamics of free and proteinogenic amino acids in a series of continuous culture experiments with Escherichia coli. The results indicated that the effect of protein degradation on the (13)C enrichment of FAAs was negligible under cellular growth conditions. Furthermore, they showed that the time scale necessary for (13)C enrichment dynamics of FAAs to reach a steady state depends on culture conditions such as oxygen uptake rate, which was likely due to different pool sizes of intracellular metabolites. The results demonstrate the importance of analyzing (13)C enrichment dynamics for the precise estimation of metabolic fluxes using FAA data. PMID- 22069097 TI - A special issue on sleep. PMID- 22069098 TI - Immunohistochemical detection of dopamine D2 receptors in neuroendocrine tumours. AB - BACKGROUND: Recently, dopamine D2 receptors (RD2) have been found to be expressed in neuroendocrine tumours (NET), the tumours which arise from the diffuse neuroendocrine cells. Moreover, successful trials of the treatment of NET with cabergoline - D2 agonist, have been reported. These findings increase the interest of investigating RD2 expression in NET. MATERIAL AND METHODS: The expression of RD2 was investigated immunohistochemically using the antibody which recognises both short (S) and long (L) isoforms of the receptor in 17 NET samples taken from 15 patients. RESULTS: In 17 NET samples, a positive reaction with the anti-RD2 antibody occurred in 11 cases. In six cases, the localisation of the immunostaining was cytoplasmic and in nine cases it was nuclear. Only in one case was the receptor cell membrane-located, and in two cases the immunoreaction was also localised in the blood vessels walls. The relation between RD2 expression and the grade of malignancy examined by means of Ki-67 antigen expression needs further study. However, preliminary observations indicate that the nuclear localisation of RD2 is linked to higher tumour malignancy. The next investigated question was the co-expression of somatostatin and dopamine receptors. This question seems important because of the perspectives of somatostatin-dopamine chimeras application in NET treatment. In the samples examined by us, RD2 were co expressed in 5/10 cases with sstr1, in 3/10 with sstr2A, in 2/9 with sstr2B, in 3/10 with sstr3, and in 5/10 with sstr5. CONCLUSION: Dopamine D2 receptors are revealed by means of immunohistochemistry in the majority of NET. They exhibit cytoplasmic and/or nuclear localisations, the latter being possibly linked to a higher grade of malignancy, and are often co-expressed with somatostatin receptors (mostly with subtypes1 and 5). PMID- 22069099 TI - Efficacy and safety of 90Y-DOTATATE therapy in neuroendocrine tumours. AB - BACKGROUND: The aim of this study was to assess the efficacy and toxicity of peptide receptor radionuclide therapy (PRRT) with the use of the high affinity somatostatin receptor subtype 2 analogue, (90)Y labelled Tyr3-octreotate, ((90)Y DOTATATE) in neuroendocrine tumours (NETs). MATERIAL AND METHODS: 46 patients with disseminated or non-operable NET were enrolled in this study. The (90)Y DOTATATE therapeutic activity was calculated per total body surface area up to a total of 7.4 GBq/m(2) administered in three to five cycles, repeated every four to nine weeks. Before and after the therapy, blood tests for haematology, kidney and liver function, and chromogranin A were performed. RESULTS: Out of 46 (90)Y DOTATATE treated patients, one died before completing the therapy and 16 died after completing the therapy, among them one due to myocardial infarction. After 12 month follow-up, stabilisation of disease was observed in 47%, partial remission in 31%, and progression in 9% of the 45 patients who completed the therapy. Five patients died before completion of 12 months of follow-up. One of the patients died due to myocardial infarction. In one case, the information after 12 months is incomplete. The progression free survival was 37.4 months. During 12 months follow-up, transient decrease of PLT, WBC and haemoglobin values was observed. A transient increase of creatinine level (within normal ranges) and decrease of GFR values were found. CONCLUSIONS: NETs (90)Y-DOTATATE therapy results in symptomatic relief and tumour mass reduction. The mild critical organ toxicity does not limit the PRRT of NETs. PMID- 22069100 TI - The predictive value of the IGF-1 level in acromegaly patients treated by surgery and a somatostatin analogue. AB - BACKGROUND: We evaluated the predictive value of IGF-1 against hGH in the treatment outcome. MATERIAL AND METHODS: A prospective study was undertaken of 47 patients (mean age 41.1 +/- 12.9 years; 44 with macroadenoma and 3 with microadenoma), requiring treatment with octreotide LAR (SSLAR) following incomplete surgery. Concentrations of hGH and IGF-1 were measured three months after surgery and three, six, nine, 12, 18, and 24 months after introducing SSLAR. RESULTS: Following surgery, respective median values of hGH and IGF-1 concentrations were 5.55 ng/mL (IQR = 7.1) and 512.7 ng/mL (IQR = 379.5). After six, 12, and 24 months of SSLAR treatment, median values of hGH decreased significantly: to 2.95 ng/mL (IQR = 5.5, p < 0.05), 2.95 ng/mL (IQR = 4.4, p < 0.05) and 2.00 ng/mL (IQR = 3.6, p < 0.001), respectively. After six, 12, and 24 months of SSLAR treatment, the respective median IGF-1 concentrations significantly decreased to 384.5 ng/mL (IQR = 312.2, p < 0.01), 323.0 ng/mL (IQR = 230.3, p < 0.001) and 334.0 ng/mL (IQR = 328.9, p < 0.01). The differences between median hGH and IGF-1 concentrations at 12 and 24 months were not significant. A statistically significant correlation was found between IGF-1 concentration prior to and after surgery (R = 0.61, p < 0.05) and prior to SSLAR treatment and IGF-1 concentration 24 months later (R = 0.49, p < 0.05). No such correlation was observed for hGH. CONCLUSIONS: The level of IGF-1 prior to surgery and prior to SSLAR treatment is a better predictor of the treatment outcome than hGH. Octreotide LAR was most effective over the first 12 months of treatment. No further significant decrease of hGH or IGF-1 levels was observed past this period. PMID- 22069101 TI - Fibrinogen and D-dimers levels in patients with hyperthyroidism before and after radioiodine therapy. AB - BACKGROUND: Various abnormalities of haemostasis have been described in patients with hyperthyroidism. The results of different studies point to the underlying thyroid disease, especially severity of hyperthyroidism and autoimmune processes, as important factors contributing to coagulation-fibrinolytic balance. The objective of this study was to investigate the association between hyperthyroidism (concerning severity of thyroid dysfunction and anti-thyroid perioxidase antibodies level) and plasma fibrinogen and D-dimers levels before and after radioiodine therapy. MATERIAL AND METHODS: The study included 35 non smoking, postmenopausal women, aged 51-69, with subclinical or overt hyperthyroidism treated with radioiodine. Analysis comprised serum TSH (thyroid stimulating hormone), fT4 (free thyroxine), fT3 (free triiodothyronine), TPO antibodies (anti-thyroid perioxidase) levels, and plasma D-dimers and fibrinogen levels before and 12-16 weeks and 24-28 weeks after radioiodine therapy. RESULTS: Elevated fibrinogen (3.82 g/L +/- 0.75, reference range 2-4.5 g/L) and D-dimers (674.26 ng/mL +/- 652.71, reference range 70-490 ng/mL) levels were observed in subjects with hyperthyroidism. They decreased after radioiodine therapy. A negative correlation between plasma fibrinogen and D-dimers levels and anti thyroid perioxidase antibodies level was found. TSH, fT4 and fT3 correlated with D-dimers level in overt hyperthyroidism. CONCLUSIONS: Hyperthyroidism is associated with a tendency toward hypercoagulation and hyperfibrinolysis. The changes observed in plasma fibrinogen and D-dimers levels are reversible. Fibrinogen level decreases within reference range and D-dimers level decreases almost to the upper reference range. They depend on severity and autoimmunity of the underlying thyroid disease and may be modified by restoring euthyroidism. PMID- 22069102 TI - Age, place of living and education influences the pregnancy universal thyroid function screening program attendance - questionnaire study. AB - BACKGROUND: The aim of this study was to assess attendance at the universal screening programme for thyroid function in pregnancy and attempt to evaluate the influence of age, number of past pregnancies, level of education, and place of residence on the attendance. The study was performed by means of a questionnaire. MATERIAL AND METHODS: Our study was performed on the basis of an anonymous questionnaire handed out to 543 women aged 16-45 years, on the third day of their puerperal stay in one of five obstetric wards in southern Poland. The questionnaire contained questions about participation in plasma level measurements of TSH, fT4, total T4, thyroid antibodies or thyroid ultrasound scanning at least once in pregnancy. RESULTS: The rate of attendance at any examination of thyroid function among pregnant women was 26.7%. The highest attendance rate (32.7%) was found among women living in provincial capitals or with higher education (41.3%), whereas the lowest was among women who had completed only primary school (11%) and those living in county towns (15%). The number of previous pregnancies did not influence the thyroid screening attendance. Women over 21 years of age participated in this screening programme more frequently (27.1-30%). CONCLUSION: Less than one third of pregnant women participated in the thyroid function screening. Place of living, education level, and age were the main factors influencing the attendance rate. PMID- 22069103 TI - Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia. AB - BACKGROUND: Thyroid autoimmunity has been suggested as a risk factor for atherosclerosis independent of thyroid function in several studies. The aim of this study was to investigate whether thyroid autoimmunity had any effect on hyperlipidaemia, obesity and abdominal obesity independent of thyroid function. MATERIAL AND METHODS: 184 premenopausal female patients with Hashimoto's thyroiditis (HT) and 150 healthy premenopausal female volunteers as control group (CG) were included in the study. According to thyroid function status, the patients were divided into three subgroups: overt hypothyroid patients (ohp), subclinical hypothyroid patients (shp) and euthyroid patients (ep). Body mass index (BMI), waist to hip ratios, waist circumference (WC), and serum lipid levels of all the participants were determined. These parameters of ep were compared with those of ohp, shp and CG. Relationships among thyroid stimulating hormone (TSH), thyroid autoantibodies and lipid levels were investigated. RESULTS: There were no significant differences between serum total cholesterol and low density lipoprotein cholesterol (LDL-C) levels of ohp and ep with HT (P = 0.18, P = 0.07 respectively) and LDL-C levels of ep were higher than those of CG (P = 0.03, P = 0.042, respectively). Although TSH levels did not correlate with serum lipid levels, levels of anti-thyroid peroxidase antibody correlated with triglyceride levels and WCs (r = 0.158; P = 0.013, r = 0.128; P = 0.048 respectively) and negatively correlated with high density lipoprotein cholesterol (HDL-C) levels (r = -0.137; P = 0.031). Levels of anti-thyroglobulin antibody also correlated with triglyceride and nonHDL-C levels (r = 0.208; P = 0.007, r = 0.158; P = 0.043 respectively). CONCLUSION: Thyroid autoimmunity may have some effects on hyperlipidaemia and abdominal obesity independent of thyroid function. PMID- 22069104 TI - Relation of leptin, adiponectin and insulin resistance to bone mineral density in type 2 diabetic postmenopausal women. AB - BACKGROUND: Our aim is to identify the relation of leptin, adiponectin and insulin resistance to bone mineral density (BMD) in type 2 diabetic postmenopausal women and compare it with that experienced by nondiabetics. MATERIAL AND METHODS: Seventy six postmenopausal female patients were included in the study. Postmenopausal type 2 diabetic (n = 19) and nondiabetic patients (n = 19) with spine and/or hip BMD T score lower than -2 were included in the study, and postmenopausal type 2 diabetic (n = 20) and nondiabetic women (n = 18) with normal BMD (T score > -1) were selected as control groups. Those receiving therapy for osteoporosis, over the age of 65, those who had a disease and were taking a medication that could affect bone metabolism were excluded. Biochemical tests, as well as leptin, adiponectin and insulin levels, were measured and insulin resistance was calculated using the HOMA test. RESULTS: There was no correlation between low BMD and leptin, adiponectin and insulin resistance. There was only a negative correlation between leptin and femur Ward's triangle BMD. CONCLUSION: Further large-scale studies must to be performed in order to analyse the effects of leptin, adiponectin and insulin resistance on bone metabolism in type 2 diabetic patients. PMID- 22069105 TI - Increased risk of type 1 diabetes in Polish children - association with INS-IGF2 5'VNTR and lack of association with HLA haplotype. AB - BACKGROUND: Human leukocyte antigens (HLA) complex and INS-IGF2 5'VNTR loci are principal determinants of the risk of type 1 diabetes mellitus (T1DM). Carriage of class III allele is protective, while class I/I homozygosity increases the risk of T1DM. MATERIAL AND METHODS: HLA and 5'VNTR allele frequencies were summarised and multivariate logistic regression models with interaction evaluation were employed to determine the presence and types of allele effect interdependency. The study group was planned to number 590 children who would undergo genotyping of 5'VNTR and HLA. RESULTS: 590 patients (302 with T1DM and 288 controls) were recruited. Frequencies of HLA risk alleles were: 117 carriers of DR3-DQ2; 130 carriers of DR4-DQ8 including 43 DR3-DQ2/DR4-DQ8 heterozygotes. In all cases, risk alleles were vastly overrepresented in the T1DM group compared to the controls (p < 0.0001 in all cases). The most frequent protective haplotype was DQB1 * 0602 observed in 24 controls and two T1DM cases (p < 0.001). Class I 5'VNTR homozygotes constituted 58% of the control group (n = 174) and 78% (n = 224) of T1DM patients [OR = 2.63 (95% CI: 1.79-3.57)]. Interactions between 5'VNTR and DR3-DQ2 or DR4-DQ8 variants did not reach statistical significance for risk of developing T1DM (p = 0.54 and 0.24) or age at its diagnosis (p = 0.14 and 0.67 respectively). CONCLUSIONS: Interactions between HLA and 5'VNTR genotype are not of multiplicative character. Class I homozygosity at 5'VNTR is a significant risk factor of T1DM and acts independently from HLA haplotype in determining the actual risk of diabetes in children. PMID- 22069106 TI - Vascular endothelial growth factor (VEGF) - part 1: in physiology and pathophysiology. AB - Angiogenesis is an important component of many physiological processes, such as the female sexual cycle, placenta formation, the processes of growth and differentiation of tissues, and reparative processes including wound healing, fracture repair, and liver regeneration. The formation of new blood vessels during angiogenesis and vasculogenesis allows the growth and functioning of multicellular organisms. Pathological angiogenesis most commonly occurs in ischaemic, inflammatory and neoplastic diseases. Conditions in the pathogenesis of which angiogenesis plays an important role are sometimes labelled angiogenic diseases. To date, a number of pro-and anti-angiogenic factors have been defined. VEGF is the only specific mitogen for endothelial cells. It stimulates their growth and inhibits apoptosis, increases vascular permeability in many tissues, promotes vasculogenesis and angiogenesis. VEGF signalling activity in relation to the cell is dependent on having its specific membrane receptors (Flt-1, KDR, Flt 4). Angiogenesis plays a protective role in ischaemic heart disease and myocardial infarction. Angiogenesis extends life for patients after a stroke. Most of the facts about physiological angiogenesis are derived from studies into liver regeneration as a result of an acute injury or partial hepatectomy. Pathological hepatic angiogenesis occurs in the course of inflammation, fibrosis, hypoxia, and during tumourogenesis. There is interesting data relating to liver steatosis and obesity. PMID- 22069107 TI - Vascular endothelial growth factor (VEGF) - part 2: in endocrinology and oncology. AB - Endocrine glands are well vascularised and the structure of their vessels facilitates the exchange of various substances, including hormones. These glands are a frequent experimental model in research on VEGF and angiogenesis. VEGF participates in the pathogenesis of diabetes. Diabetic nephropathy is in essence a microvascular disease that develops as a result of a confluence of haemodynamic and metabolic perturbations. Diabetic retinopathy is the commonest microvascular complication of diabetes mellitus and is the leading cause of blindness. In diabetic retinopathy, ischaemic states, and hence tissue hypoxia and angiogenesis, take place. The participation of angiogenesis and VEGF in the pathogenesis of neoplastic disease has been described in many papers. VEGF protein and mRNA have been found in cancers of the thyroid, bronchus, lungs, oesophagus, stomach, colon, liver, breast, ovary, uterus, kidney, and urinary bladder, and in malignant tumours of the brain and bone. There have been many reports of the connections between the degree of VEGF expression and tumour aggression and prognosis in patients. Richly vascularised are GEP NET. In neuroendocrine tumours, strong expression of VEGF, Flt-1 and KDR in relation to the unchanged surrounding tissues has been demonstrated. Depending on the disease entity or the degree of its severity, attempts to apply angiogenic and antiangiogenic therapy have being made. Antiangiogenic therapy (usually regarded as a form of cancer therapy) is based on: 1. inhibitory effects of proangiogenic ligands and their receptors; 2. stimulation or delivery of angiogenesis inhibitors; and 3. direct destruction of neoplastic tumour vasculature. PMID- 22069108 TI - Suppurative thyroiditis caused by Salmonella enteritidis. AB - Bacterial thyroiditis is a rare disease, and one of which the clinical symptoms and signs are frequently misleading. On the other hand, prompt diagnosis is crucial for successful treatment. We report the case of an 82 year-old man with diabetes mellitus type 2 and a history of steroid treatment who presented with severe odynophagia and dysphagia associated with fever, chills, sore throat and right ear pain. Based on the clinical picture, radiological studies, thyroid cytology, blood and thyroid aspirate culture, suppurative thyroiditis caused by Salmonella enteritidis was diagnosed. The patient was successfully treated with antibiotics and surgical drainage. PMID- 22069109 TI - Transplantation osteoporosis. AB - Transplantation provides a valuable, often life-saving, treatment for end-stage failure of many organs, including the heart, kidneys, liver, pancreas and lungs. It is also an important therapeutic option in diseases of the bone marrow and the immune system. Despite the undoubted benefits for transplant patients, it is associated with an increased risk of many complications. The potential causes include: poor general health of the patient, heavy burden of the surgery itself and the need for the long-term use of immunosuppression. In addition, the patients are also on numerous other medications, e.g. anti-coagulants, diuretics. Osteoporosis and high risk of fractures have emerged as frequent and devastating complications of the transplantation process. This article provides a review of the current literature on osteoporosis after transplantation, and the treatment options for this serious illness. PMID- 22069110 TI - Improved synthesis and mutagenicity of oligonucleotides containing 5 hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. AB - 5-Formylcytosine (fC or (5-CHO)dC) and 5-carboxylcytosine (caC or (5-COOH)dC) have recently been identified as constituents of mammalian DNA. The nucleosides are formed from 5-methylcytosine (mC or (5-Me)dC) via 5-hydroxymethylcytosine (hmC or (5-HOMe)dC) and are possible intermediates of an active DNA demethylation process. Here we show efficient syntheses of phosphoramidites which enable the synthesis of DNA strands containing these cytosine modifications based on Pd(0) catalyzed functionalization of 5-iododeoxycytidine. The first crystal structure of fC reveals the existence of an intramolecular H-bond between the exocyclic amine and the formyl group, which controls the conformation of the formyl substituent. Using a newly designed in vitro mutagenicity assay we show that fC and caC are only marginally mutagenic, which is a prerequisite for the bases to function as epigenetic control units. PMID- 22069111 TI - Antidepressant effects of magnetic resonance imaging--based stimulation on major depressive disorder: a double-blind randomized clinical trial. AB - Antidepressant effects of magnetic resonance imaging (MRI) based stimulation have been reported in animal studies, but no human studies are available on subjects with major depressive disorder. Here, the efficacy of two diagnostic MRI protocols (echo-planar diffusion-weighted imaging (DWI) and T1-weighted imaging) was assessed in patients with major depressive disorder. In this double-blind randomized clinical trial, 51 patients with clinically proven major depressive disorder were randomly enrolled into three equal groups. All patients were receiving a selective serotonin reuptake inhibitor as the only antidepressant treatment. The first group received echo-planar DW stimulation (DWI group), the second group received T1-weighted stimulation (T1 group), and the third group experienced a similar condition without receiving any magnetic stimulation (sham group). The Hamilton rating scale for depression (HAMD24) and Beck depression inventory (BDI) were used to assess the effect of MR stimulation on depressive symptoms. In comparison to baseline, mean HAMD24 and BDI scores significantly (p < 0.001) decreased in the DWI (by 35% and 39%) and T1 (by 38% and 39%) groups 2 weeks after MR stimulation. In the sham group, reduction in HAMD24 (19%, p = 0.04) and BDI score (15%, p = 0.07) were lower than the MR stimulation groups. Two weeks after the MR experiments, changes in mean HAMD24 score and BDI score were significantly (p < 0.05) higher in subjects treated with MR stimulation (DWI or T1) vs. sham group. In conclusion, this study demonstrated the antidepressant effects of DWI and T1 MRI protocols. Our results may point to usefulness of MR stimulation for clinical use in patients with major depressive disorder. PMID- 22069112 TI - Barriers to staff adoption of a surgical safety checklist. AB - OBJECTIVE: Implementation of a surgical checklist depends on many organisational factors and on socio-cultural patterns. The objective of this study was to identify barriers to effective implementation of a surgical checklist and to develop a best use strategy. SETTING: 18 cancer centres in France. DESIGN: The authors first assessed use compliance and completeness rates of the surgical checklist on a random sample of 80 surgical procedures performed under general or loco-regional anaesthesia in each of the 18 centres. They then developed a typology of the organisational and cultural barriers to effective checklist implementation and defined each barrier's contents using data from collective and semi-structured individual interviews of key staff, the results of an email questionnaire sent to the 18 centres, and direct observations over 20 h in two centres. RESULTS: The study consisted of 1440 surgical procedures, 1299 checklists, and 28 578 items. The mean compliance rate was 90.2% (0, 100). The mean completion rate was 61% (0, 84). 11 barriers to effective checklist implementation were identified. Their incidence varied widely across centres. The main barriers were duplication of items within existing checklists (16/18 centres), poor communication between surgeon and anaesthetist (10/18), time spent completing the checklist for no perceived benefit, and lack of understanding and timing of item checks (9/18), ambiguity (8/18), unaccounted risks (7/18) and a time-honoured hierarchy (6/18). CONCLUSIONS: Several of the barriers to the successful implementation of the surgical checklist depended on organisational and cultural factors within each centre. The authors propose a strategy for change for checklist design, use and assessment, which could be used to construct a feedback loop for local team organisation and national initiatives. PMID- 22069114 TI - Do older patients' perceptions of safety highlight barriers that could make their care safer during organisational care transfers? AB - BACKGROUND: Healthcare is a series of complex, interwoven systems in which any discontinuities of care may affect the safety of patients, who have been reported to perceive safety differently to clinicians. This study aimed to explore patient perceptions of safety and identify how they can be used to construct additional barriers to reduce safety incidents within organisational care transfers, which are known to be high in risk. DESIGN: Appreciative Inquiry (AI) methodology was used to develop semi-structured interviews, using the Discover and Dream processes of AI. Fourteen patients (four men, 10 women; average age 76.2 years) were purposively recruited from NHS community care teams, social care homes and private nursing homes based on their experience of going through organisational care transfers. Thematic analysis was used to highlight key themes, which participants verified. FINDINGS: Communication, responsiveness and avoidance of traditional safety risks were identified as being important for patients to feel safe. Communication and responsiveness were mapped onto the Swiss-Cheese model of safety, presenting two new barriers to safety incidents. Traditional risks and the role of trust are discussed in relation to patients feeling safe. CONCLUSION: Perceptions of safety such as communication and responsiveness were similar to those found in previous studies. Mapping these perceptions onto the Swiss-Cheese model of safety identifies how further defences, barriers and safeguards can be constructed to make people feel safer by reinforcing communication and responsiveness. Traditional risks are widely published, but the identification by patients reinforces the role they can play in identifying and reporting these risks. PMID- 22069113 TI - Effects of a multicentre teamwork and communication programme on patient outcomes: results from the Triad for Optimal Patient Safety (TOPS) project. AB - BACKGROUND: Improving communication between caregivers is an important approach to improving safety. OBJECTIVE: To implement teamwork and communication interventions and evaluate their impact on patient outcomes. DESIGN: A prospective, interrupted time series of a three-phase INTERVENTION: a run-in period (phase 1), during which a training programme was given to providers and staff on each unit; phase 2, which focused on unit-based safety teams to identify and address care problems using skills from phase 1; and phase 3, which focused on engaging patients in communication efforts. SETTING: General medical inpatient units at three northern California hospitals. PATIENTS: Administrative data were collected from all adults admitted to the target units, and a convenience sample of patients interviewed during and after hospitalisation. MEASUREMENTS: Readmission, length of stay and patient reports of teamwork, problems with care, and overall satisfaction. RESULTS: 10 977 patients were admitted; 581 patients (5.3% of total sample) were interviewed in hospital, and 313 (2.9% overall, 53.8% of interviewed patients) completed 1-month surveys. No phase of the study was associated with adjusted differences in readmission or length of stay. The phase 2 intervention appeared to be associated with improvement in reports of whether physicians treated them with respect, whether nurses treated them with respect or understood their needs (p<0.05 for all). Interestingly, patients were more likely to perceive that an error took place with their care and agreed less that their caregivers worked well together as a team. No phase had a consistent impact on patient reports of care processes or overall satisfaction. Limitations The study lacks direct measures of patient safety. CONCLUSIONS: Efforts to simultaneously improve caregivers' ability to troubleshoot care and enhance communication may improve patients' perception of team functions, but may also increase patients' perception of safety gaps. PMID- 22069115 TI - Getting the message: a quality improvement initiative to reduce pages sent to the wrong physician. AB - BACKGROUND: One in seven pages are sent to the wrong physician and may result in unnecessary delays that potentially threaten patient safety. The authors aimed to implement a new team-based paging process to reduce pages sent to the wrong physician. METHODS: The authors redesigned the paging process on general internal medicine (GIM) wards at a Canadian academic medical centre by implementing a standardised team-based paging process (pages directed to one physician responsible for receiving pages on behalf of the entire physician team) using rapid-cycle change methods. The authors evaluated the intervention using a controlled before-after study design by measuring pages sent to the wrong physician before and after implementation of the redesigned paging process. RESULTS: Pages sent to the wrong physician from the GIM (intervention) wards decreased from 14% to 3% (11% reduction), while pages sent to the wrong physician from control wards fell from 13% to 7% (6% reduction). The difference between the intervention wards and the control wards was significant (5% greater reduction in the intervention group compared with the control group, p=0.008). Nurses were more satisfied with team-based paging than the existing paging process. Team based paging may, however, introduce changes in communication workflow that lead to increased paging interruptions for certain members of the physician team. CONCLUSIONS: The authors successfully redesigned the hospital's paging process to decrease pages sent to the wrong physician. They recommend that the frequency of pages sent to the wrong physician is measured and changes be implemented to paging processes to reduce this error. PMID- 22069116 TI - Systems human factors: how far have we come? PMID- 22069117 TI - Mothers' differential treatment of adolescent siblings: predicting college attendance of sisters versus brothers. AB - Current estimates suggest that by 2015, 60% of college students will be women, a change since 1970 when 59% were men. We investigated family dynamics that might explain the growing gender gap in college attendance, focusing on an ethnically diverse sample of 522 mixed sex sibling dyads from the National Longitudinal Study of Adolescent Health. We examined whether the difference between sisters' and brothers' reports of their mothers' expectations for, and involvement in, their education during adolescence predicted their differential odds of college attendance seven years later. Sisters were more likely than brothers to attend college, and this gap was more pronounced among non-Whites and non-Asians. Sisters also had higher grades in school than their brothers. Although there were no gender differences overall in maternal educational expectations or involvement, brothers reported greater maternal involvement than sisters in non White and non-Asian families. After controlling for family background factors, the average of siblings' reports of maternal treatment, and differences between siblings' grades, the results revealed that as sisters reported greater maternal educational expectations than their brothers, it became more likely that only the sister rather than only the brother in the family attended college. The difference between brothers' and sisters' reports of their mothers' educational involvement and their odds of attending college showed the same pattern of association but was not statistically significant. These results suggest that within-family social comparisons may play a role in sisters' and brothers' choices about attending college. PMID- 22069118 TI - Domestication bottlenecks limit genetic diversity and constrain adaptation in narrow-leafed lupin (Lupinus angustifolius L.). AB - In contrast to most widespread broad-acre crops, the narrow-leafed lupin (Lupinus angustifolius L.) was domesticated very recently, in breeding programmes isolated in both space and time. Whereas domestication was initiated in Central Europe in the early twentieth century, the crop was subsequently industrialized in Australia, which now dominates world production. To investigate the ramifications of these bottlenecks, the genetic diversity of wild (n = 1,248) and domesticated populations (n = 95) was characterized using diversity arrays technology, and adaptation studied using G * E trials (n = 31) comprising all Australian cultivars released from 1967 to 2004 (n = 23). Principal coordinates analysis demonstrates extremely limited genetic diversity in European and Australian breeding material compared to wild stocks. AMMI analysis indicates that G * E interaction is a minor, albeit significant effect, dominated by strong responses to local, Western Australian (WA) optima. Over time Australian cultivars have become increasingly responsive to warm, intermediate rainfall environments in the northern WA grainbelt, but much less so to cool vegetative phase eastern environments, which have considerably more yield potential. G * E interaction is well explained by phenology, and its interaction with seasonal climate, as a result of varying vernalization responses. Yield differences are minimized when vegetative phase temperatures fully satisfy the vernalization requirement (typical of eastern Australia), and maximized when they do not (typical of WA). In breeding for WA optima, the vernalization response has been eliminated and there has been strong selection for terminal drought avoidance through early phenology, which limits yield potential in longer season eastern environments. Conversely, vernalization-responsive cultivars are more yield-responsive in the east, where low temperatures moderately extend the vegetative phase. The confounding of phenology and vernalization response limits adaptation in narrow leafed lupin, isolates breeding programmes, and should be eliminated by widening the flowering time range in a vernalization-unresponsive background. Concomitantly, breeding strategies that will widen the genetic base of the breeding pool in an ongoing manner should be initiated. PMID- 22069119 TI - Identification, validation and high-throughput genotyping of transcribed gene SNPs in cassava. AB - The availability of genomic resources can facilitate progress in plant breeding through the application of advanced molecular technologies for crop improvement. This is particularly important in the case of less researched crops such as cassava, a staple and food security crop for more than 800 million people. Here, expressed sequence tags (ESTs) were generated from five drought stressed and well watered cassava varieties. Two cDNA libraries were developed: one from root tissue (CASR), the other from leaf, stem and stem meristem tissue (CASL). Sequencing generated 706 contigs and 3,430 singletons. These sequences were combined with those from two other EST sequencing initiatives and filtered based on the sequence quality. Quality sequences were aligned using CAP3 and embedded in a Windows browser called HarvEST:Cassava which is made available. HarvEST:Cassava consists of a Unigene set of 22,903 quality sequences. A total of 2,954 putative SNPs were identified. Of these 1,536 SNPs from 1,170 contigs and 53 cassava genotypes were selected for SNP validation using Illumina's GoldenGate assay. As a result 1,190 SNPs were validated technically and biologically. The location of validated SNPs on scaffolds of the cassava genome sequence (v.4.1) is provided. A diversity assessment of 53 cassava varieties reveals some sub structure based on the geographical origin, greater diversity in the Americas as opposed to Africa, and similar levels of diversity in West Africa and southern, eastern and central Africa. The resources presented allow for improved genetic dissection of economically important traits and the application of modern genomics-based approaches to cassava breeding and conservation. PMID- 22069120 TI - Analysis of current treatments used in clinical practice in a pediatric summer camp population for children with inflammatory bowel disease. AB - BACKGROUND: Many treatment options exist for children with inflammatory bowel disease (IBD), yet the lack of clinical guidelines for management has lead to great variation in care. The purpose of this project was to evaluate current treatment modalities in children from the Northeast US who applied to the 2010 session of Camp Oasis, a Crohn's and Colitis Foundation of America (CCFA) sponsored camp for children ages 8-17 with medically stable IBD. METHODS: Patient demographics, medical history, and current medications were entered into the camp database. The subjects were divided into two groups; Crohn's disease (CD) or ulcerative colitis/indeterminate colitis (UC/IC). In all, 164 applicants were included, 121 (74%) with CD and 43 (26%) with UC/IC. RESULTS: There were no significant differences between the two groups with respect to median age at the time of camp, median age at diagnosis, or median length of illness. Of the 121 applicants with CD, 13 (10.7%) were on an antibiotic, 56 (46.3%) were on a 5 aminosalicylate (5-ASA), 10 (8.3%) were on corticosteroids, 57 (47.1%) were on immunomodulators, and 44 (36.4%) were on a biologic agent. Six (5%) were on both an immunomodulator and a biologic agent. Of the 43 subjects with UC/IC, 27 (62.7%) were on a 5-ASA, two (4.7%) were on corticosteroids, 13 (30.2%) were on an immunomodulator, and four (9.3%) were on a biologic agent. The groups were similar with regard to surgery (20.7% for CD and 18.6% for UC/IC). CONCLUSIONS: Identifying current treatment patterns may serve to highlight variations in care among this pediatric IBD population. PMID- 22069121 TI - Treating and downstaging hepatocellular carcinoma in the caudate lobe with yttrium-90 radioembolization. AB - PURPOSE: This study was designed to determine the technical feasibility, safety, efficacy, and potential to downstage patients to within transplantation criteria when treating patients with hepatocellular carcinoma (HCC) of the caudate lobe using Y90 radioembolization. METHODS: During a 4-year period, 8 of 291 patients treated with radioembolization for unresectable HCC had disease involving the caudate lobe. All patients were followed for treatment-related clinical/biochemical toxicities, serum tumor marker response, and treatment response. Imaging response was assessed with the World Health Organization (WHO) and European Association for the Study of the Liver (EASL) classification schemes. Pathologic response was reported as percent necrosis at explantation. RESULTS: Caudate lobe radioembolization was successfully performed in all eight patients. All patients presented with both cirrhosis and portal hypertension. Half were United Network for Organ Sharing (UNOS) stage T3 (n = 4, 50%). Fatigue was reported in half of the patients (n = 4, 50%). One (13%) grade 3/4 bilirubin toxicity was reported. One patient (13%) showed complete tumor response by WHO criteria, and three patients (38%) showed complete response using EASL guidelines. Serum AFP decreased by more than 50% in most patients (n = 6, 75%). Four patients (50%) were UNOS downstaged from T3 to T2, three of who underwent transplantation. One specimen showed histopathologic evidence of 100% complete necrosis, and two specimens demonstrated greater than 50% necrosis. CONCLUSIONS: Radioembolization with yttrium-90 appears to be a feasible, safe, and effective treatment option for patients with unresectable caudate lobe HCC. It has the potential to downstage patients to transplantation. PMID- 22069122 TI - An update on the pathology and clinical management of gouty arthritis. AB - Gouty arthritis is an inflammatory condition associated with debilitating clinical symptoms, functional impairments, and a substantial impact on quality of life. This condition is initially triggered by the deposition of monosodium urate crystals into the joint space. This causes an inflammatory cascade resulting in the secretion of several proinflammatory cytokines and neutrophil recruitment into the joint. While generally effective, currently available agents are associated with a number of adverse events and contraindications that complicate their use. Based on our increased understanding of the inflammatory pathogenesis of gouty arthritis, several new agents are under development that may provide increased efficacy and reduced toxicity. PMID- 22069123 TI - Agricultural injury risk among rural California public high school students: prospective results. AB - OBJECTIVES: To characterize prospective agricultural injury experience among rural California Central Valley public high school students enrolled in agricultural sciences curriculum. METHODS: The University of California, Davis Youth Agricultural Injury Study (UCD-YAIS) examined prospective farm-work injury among students from 10 California Central Valley public high schools. RESULTS: Of eligible subjects, 882 (62.5%) completed at least one annual follow-up survey. Of these, 489 reported farm work in the previous year, including 40 (8.2%) with at least one farm work-related injury. Fractures were the most common injury, especially among girls. Girls were more likely to suffer animal-related injury and boys injury from motor vehicles, machinery, or tool use. Prospective injury risk was strongly associated with prior-year farm injury (OR 8.53; 95% CI 4.02, 18.1) and farm work hours. After adjustment for farm work hours, grade level, and sex, risk was significantly associated with machinery operation, applying chemicals, number of hazardous tasks performed, riding motorcycles or mopeds, riding in back of an uncovered pick-up truck, and smoking. Risky attitude toward farm safety was associated prospectively with injury in stepwise fashion. CONCLUSIONS: Adolescents are at risk for serious farm-work injuries. Although limitations on hazardous tasks and farm work hours are likely to be the most efficacious means for reducing injury, education will play an important role. Education should include inculcating safety-related attitudes and habits and focus on hazardous tasks, such as those involving animals (for girls) and motor vehicles and machinery (for boys), especially among youth with prior farm injury. PMID- 22069124 TI - Calpain 2-dependent IkappaBalpha degradation mediates CPT-11 secondary resistance in colorectal cancer xenografts. AB - CPT-11 (irinotecan), the first-line chemotherapy for advanced stage colorectal cancer, remains inactive in about half of patients (primary chemoresistance) and almost all initial responders develop secondary resistance after several courses of treatment (8 months on average). Nude mice bearing HT-29 colon cancer xenografts were treated with CPT-11 and/or an NF-kappaB inhibitor for two courses. We confirm that NF-kappaB inhibition potentiated CPT-11 anti-tumoural effect after the first course of treatment. However, tumours grew again at the end of the second course of treatment, generating resistant tumours. We observed an increase in the basal NF-kappaB activation in resistant tumours and in two resistant sublines, either obtained from resistant HT-29 tumours (HT-29R cells) or generated in vitro (RSN cells). The decrease of NF-kappaB activation in HT-29R and RSN cells by stable transfections with the super-repressor form of IkappaBalpha augmented their sensitivity to CPT-11. Comparing gene expression profiles of HT-29 and HT-29R cells, we identified the S100A10/Annexin A2 complex and calpain 2 as over-expressed potential NF-kappaB inducers. SiRNA silencing of calpain 2 but not of S100A10 and/or annexin A2, resulted in a decrease in NF kappaB activation, an increase in cellular levels of IkappaBalpha and a partial restoration of the CPT-11 sensitivity in both HT-29R and RSN cells, suggesting that calpain 2-dependent IkappaBalpha degradation mediates CPT-11 secondary resistance. Thus, targeted therapies directed against calpain 2 may represent a novel strategy to enhance the anti-cancer efficacy of CPT-11. PMID- 22069125 TI - Obesity: the greatest epidemic of the 21st century? PMID- 22069126 TI - Who are the low-risk patients that could benefit from watch-and-wait regarding the neck? AB - CONTEXT AND OBJECTIVE: The management of clinically negative neck is controversial, with an ongoing debate on the indication criteria and prognostic impact of different types of therapy. The aim here was to compare the results from neck dissection and watch-and-wait, among oral cancer patients who, clinically, did not show any evidence of neck metastasis. DESIGN AND SETTING: Retrospective analysis in a tertiary cancer center hospital. METHODS: Patients with epidermoid oral carcinoma were assessed. The inclusion criteria were: primary tumor restricted to the oral/oropharyngeal cavity, no previous treatment, surgical treatment as the first option, clinical/radiological stage N0 and no distant metastasis. RESULTS: Two hundred and sixty-two patients were analyzed. The length of follow-up ranged from four to 369.6 months and, at the end, 118 patients were alive, 53 had died due to cancer, 84 had died from other causes and 7 had died after the operation. Among the patients who underwent neck dissection, lymphatic vascular embolization (P = 0.009) and tumor thickness (P = 0.002) were significant for regional recurrence, while for the watch-and-wait group, only tumor thickness was significant (P = 0.018). Through recursive partitioning, the patients without adverse prognostic factors and tumor thickness < 2 mm presented compatible results in the two groups. CONCLUSION: Elective neck dissection seems to be the best treatment option. Patients who are eligible for watch-and-wait constitute a small group that, ideally, is categorized according to the postoperative pathological findings. PMID- 22069127 TI - Costs and usage of healthcare services before and after open bariatric surgery. AB - CONTEXT AND OBJECTIVE: Morbidly obese individuals are major consumers of healthcare services, with high associated costs. Bariatric surgery is an alternative for improving these individuals' comorbidities. There are no studies comparing costs before and after bariatric surgery in Brazil. The aim here was to analyze results relating to healthcare usage and direct costs among morbidly obese patients undergoing bariatric surgery. DESIGN AND SETTING: Historical cohort study on patients receiving healthcare through a private health plan in Belo Horizonte, Minas Gerais. METHODS: All healthcare services and their associated costs were included in the analysis: hospitalization, hospital stay, elective outpatient consultations, emergency service usage and examinations. The analyses were treated as total when including the whole years before and after surgery, or partial when excluding the three-month periods adjacent to the operation. RESULTS: For 382 obese patients who underwent open bariatric operations, there were 53 hospitalizations one year before and 95 one year after surgery (P = 0.013). Gastrointestinal complications were the main indications for post-procedure hospitalizations. The partial average cost almost doubled after the operation (US$ 391.96 versus US$ 678.31). In subgroup analysis, the costs from patients with gastrointestinal complications were almost four times greater after bariatric surgery. Even in the subgroup without complications, the partial average cost remained significantly higher. CONCLUSION: Although bariatric surgery is the only path towards sustained weight loss for morbidly obese patients, the direct costs over the first year after the procedure are greater. Further studies, with longer follow-up, might elucidate whether long-term reversal of this trend would occur. PMID- 22069128 TI - Prevalence of prediabetes in patients with metabolic risk. AB - CONTEXT AND OBJECTIVE: Early diagnosis of prediabetes should be done to avoid complications relating to diabetes mellitus (DM). The aim here was to assess the prevalence of prediabetes among individuals at high risk of developing DM, and to seek variables relating to glucose intolerance (GI) among individuals with normal fasting plasma glucose (FPG). DESIGN AND SETTING: Cross-sectional study at Hospital do Servidor Publico Estadual, Sao Paulo. METHODS: The FPG and glucose tolerance test (GTT) were analyzed, from which the subjects were divided as follows: group 1 (FPG and GTT both normal), group 2 (normal FPG but abnormal GTT), group 3 (abnormal FPG but normal GTT), and group 4 (FPG and GTT both abnormal). The subjects' clinical, laboratory and anthropometric profile was determined. RESULTS: 138 subjects were studied: 44 in group 1, 11 in group 2, 33 in group 3 and 50 in group 4. The prevalence of prediabetes was 68.0%. Group 4 individuals were older than group 1 individuals [69.0 (55.5-74.0) versus 58.9 +/- 11.8 years; P < 0.05], with greater prevalence of risk conditions for DM [5.0 (4.0-5.0) versus 4.0 (3.0-5.0); P < 0.05]. Among individuals with normal FPG, GI prevalence was 20.0%. No variables analyzed correlated with GTT. CONCLUSION: The prevalence of prediabetes was 68.0%, and 20.0% of subjects with normal FPG had GI. Although some anthropometric, clinical and laboratory variables have been correlated with DM and prediabetes, none, except for GTT, was able to screen for GI among subjects with normal FPG in the present study. PMID- 22069129 TI - Prevalence of breast cancer in the city of Goiania, Goias, Brazil, between 1988 and 2002. AB - CONTEXT AND OBJECTIVE: Studies have shown increased prevalence rates for breast cancer, relating to higher incidence, longer survival and breast cancer prevention programs among populations. The aim here was to analyze the annual prevalence of breast cancer in Goiania over a 15-year period. DESIGN AND SETTING: This was a cross-sectional study on women with breast cancer diagnosed in Goiania, Goias, Brazil, from 1988 to 2002. METHODS: The breast cancer cases were identified in the database of the Population-Based Cancer Registry of Goiania. The 15-year period was stratified into three five-year periods. The cases were followed up for five years, and the mortality database was used to exclude deaths. The population of the official census was used as the denominator for rate calculations. RESULTS: The coefficient of breast cancer prevalence in Goiania was 22.87/100,000 in 1988 and 220.22/100,000 women in 2002. The analyses for periods showed that in the first period, the rate was 19.39/100,000 and that it was 44.79/100,000 in the last period. For the fifteen years analyzed, the prevalence rate for breast cancer was 127.24/100,000 women. The annual percentage change was 27.07 (P < 0.001; 95% confidence interval, CI: 20.79-33.67) from 1988 to 1992 and 9.39 (P < 0.001; 95% CI: 8.52-10.25) from 1992 to 2002. CONCLUSION: There was an increase in the breast cancer prevalence rate in the city of Goiania between 1988 and 2002, possibly relating to the improvement in the screening and treatment of breast cancer. PMID- 22069130 TI - Characteristics of ascitic fluid from patients with suspected spontaneous bacterial peritonitis in emergency units at a tertiary hospital. AB - CONTEXT AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a complication of ascites, especially in cirrhosis. Ascitic fluid with 250 or more neutrophils/mm3 is an acceptable criterion for diagnosis, even when bacterial fluid cultures are negative. The aims here were to estimate SBP frequency among emergency room patients based on cellular criteria and evaluate the biochemical profile of these fluids. DESIGN AND SETTING: Retrospective study at a public tertiary hospital. METHODS: Laboratory records of patients with ascites attended in emergency rooms between November 2001 and November 2006, from whom ascitic fluid samples were sent to the laboratory due to suspected SBP, were evaluated. The 691 samples included were divided into group A (presumed SBP: >= 250 neutrophils/mm3; n = 219; 31.7%) and group B (no presumed SBP: < 250 neutrophils/mm3; n = 472; 68.3%). Patients' sex and age; ascitic fluid characteristics (numbers of neutrophils, leukocytes and nucleated cells); bacteriological characteristics; and protein, lactate dehydrogenase, adenosine deaminase and glucose concentrations were evaluated. RESULTS: Among group A cultured samples, 63 (33.8%) had positive bacterial cultures with growth of pathogens commonly associated with SBP. In total, the group A samples showed higher lactate dehydrogenase levels than seen in the group B samples. The latter presented predominance of lymphocytes and macrophages. CONCLUSION: Among the ascitic fluid samples with clinically suspected SBP, 31.7% fulfilled the cellular diagnostic criteria. Positive bacterial isolation was found in 33.8% of the cultured samples from the presumed SBP group. PMID- 22069131 TI - Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil. AB - CONTEXT AND OBJECTIVE: The Wnt pathway is involved in tumorigenesis of several tissues. For this reason, we proposed to evaluate Wnt gene expression in endometrial cancer type I. DESIGN AND SETTING: Cross-sectional study on materials gathered from the tissue bank of the Department of Pathology, Universidade Federal de Sao Paulo. METHODS: Endometrial specimens were obtained from surgeries performed between 1995 and 2005 at Sao Paulo Hospital, Universidade Federal de Sao Paulo. The material was divided into two groups according to tissue type: Group A, atrophic endometrium (n = 15); and Group B, endometrial adenocarcinoma (n = 45). We compared the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) and beta-catenin between endometrial cancer type I and atrophic endometrium. RESULTS: Regarding Wnt1, FZD1 and Wnt5a expression, no significant association was observed between the groups. A significant association was observed between the groups in relation to FZD5 expression (P = 0.001). The proportion of FZD5-positive samples was significantly higher in group A (80.0%) than in group B (31.1%). Regarding the survival curve for FZD5 in group B, we did not find any significant association between atrophic endometrium and endometrial adenocarcinoma. We also did not find any significant association regarding beta-catenin expression (P = 1.000). CONCLUSION: FZD5 is downregulated in endometrial adenocarcinoma, in comparison with atrophic endometrium. PMID- 22069132 TI - Efficacy of a specific model for cognitive-behavioral therapy among panic disorder patients with agoraphobia: a randomized clinical trial. AB - CONTEXT AND OBJECTIVE: Cognitive-behavioral therapy is frequently indicated for panic disorder. The aim here was to evaluate the efficacy of a model for cognitive-behavioral therapy for treating panic disorder with agoraphobia. DESIGN AND SETTING: Randomized clinical trial at Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro. METHODS: A group of 50 patients with a diagnosis of panic disorder with agoraphobia was randomized into two groups to receive: a) cognitive-behavioral therapy with medication; or b) medication (tricyclic antidepressants or selective serotonin reuptake inhibitors). RESULTS: Although there was no difference between the groups after the treatment in relation to almost all variables with the exception of some items of the Sheehan disability scale and the psychosocial and environmental problems scale, the patients who received the specific therapy presented significant reductions in panic attacks, anticipatory anxiety, agoraphobia avoidance and fear of body sensations at the end of the study, in relation to the group without the therapy. On the overall functioning assessment scale, overall wellbeing increased from 60.8% to 72.5% among the patients in the group with therapy, thus differing from the group without therapy. CONCLUSION: Although both groups responded to the treatment and improved, we only observed significant differences between the interventions on some scales. The association between specific cognitive behavioral therapy focusing on somatic complaints and pharmacological treatment was effective among this sample of patients with panic disorder and the response was similar in the group with pharmacological treatment alone. PMID- 22069133 TI - Lumiracoxib for acute postoperative dental pain: a systematic review of randomized clinical trials. AB - CONTEXT AND OBJECTIVE: Lumiracoxib is an anti-inflammatory drug that has been used to treat acute dental pain, mainly in postsurgical settings, in which the greatest levels of pain and discomfort are experienced during the first 24 hours. This study aimed to assess the efficacy and safety of lumiracoxib for treating acute postsurgical dental pain. DESIGN AND SETTING: Systematic review developed at the Brazilian Cochrane Centre, Universidade Federal de Sao Paulo. METHODS: An electronic search was conducted in the PubMed, Cochrane Library, Lilacs (Literatura Latino-Americana e do Caribe em Ciencias da Saude), SciELO (Scientific Electronic Library Online) and Embase databases. A manual search was also performed. Only randomized controlled trials were included, and these were selected and assessed by two researchers with regard to the risk of bias. RESULTS: Three clinical trials with 921 participants were included. Lumiracoxib 400 mg produced onset of analgesia in a shorter time than shown by lumiracoxib 100 mg, celecoxib 200 mg and ibuprofen 400 mg. There was no difference between lumiracoxib 400 mg and rofecoxib 50 mg. In two studies, the mean time taken to attain onset of analgesia for the placebo was not estimated because the number of participants who reached onset was too small. CONCLUSION: There is evidence with a moderate risk of bias that recommends the use of lumiracoxib for acute postoperative dental pain. However, the adverse effects are not completely known. Given that lumiracoxib is currently available in only three countries, further studies are likely to be rare and discouraged. PMID- 22069134 TI - Testicular adrenal rest tumor in infertile man with congenital adrenal hyperplasia: case report and literature review. AB - CONTEXT: Synthesis of cortisol and aldosterone is impaired in patients with congenital adrenal hyperplasia (CAH) because of 21-hydroxylase deficiency. Men with CAH have low fertility rates compared with the normal population, and this is related to testicular adrenal rest tumors. Findings of azoospermia in combination with a testicular tumor on ultrasound are likely to have a mechanical cause, especially when in the testicular mediastinum. The preferred treatment method consists of intensive corticoid therapy. However, when the tumor is unresponsive to steroid therapy, surgical treatment should be considered. CASE REPORT: We present the case of a male patient with CAH due to 21-hydroxylase deficiency who presented a testicular tumor and azoospermia. Treatment with low daily corticoid doses had previously been started by an endocrinologist, but after 12 months, no significant change in sperm count was found. Although the adrenocorticotrophic hormone and 17-hydroxyprogesterone levels returned to normal values, the follicle-stimulating hormone (FSH), luteinizing hormone and testosterone levels remained unchanged. Ultrasound examination confirmed that the testicles were small and heterogenous bilaterally, and revealed a mosaic area at the projection of the testis network bilaterally. Magnetic resonance imaging confirmed the finding. Testicular biopsy revealed the presence of preserved spermatogenesis and spermiogenesis in 20% of the seminiferous tubules in the right testicle. The patient underwent testis-sparing tumor resection. After 12 months of follow-up, there was no tumor recurrence but the patient still presented azoospermia and joined an intracytoplasmic sperm injection program. PMID- 22069135 TI - Cystic brain metastases radiologically simulating neurocysticercosis. AB - CONTEXT: Brain metastases are common complications of cancer. Magnetic resonance imaging (MRI), the main diagnostic imaging method in these cases, rarely shows cystic images. CASE REPORT: The patient was a 45-year-old woman who had had severe headache for a month that was refractory to medication, and had previously had breast cancer, which had been treated. The MRI showed the criteria for neurocysticercosis. Since there was no improvement with clinical treatment, we chose to excise the lesions. Histopathological analysis showed an epithelioid malignant neoplasm. CONCLUSION: From immunohistochemical analysis, it was concluded that this was a metastasis of breast carcinoma. Even when the MRI is not characteristic of cerebral metastasis, this hypothesis needs to be ruled out in patients with a previous history of cancer. PMID- 22069136 TI - Hand dysfunction in scleroderma patients. PMID- 22069137 TI - Confidential unit exclusion and blood safety. PMID- 22069140 TI - Investigations on cytotoxic and genotoxic effects of laser printer emissions in human epithelial A549 lung cells using an air/liquid exposure system. AB - Exposure to emissions from laser printers during the printing process is commonplace worldwide, both in the home and workplace environment. In the present study, cytotoxic and genotoxic effects of the emission from five low to medium throughput laser printers were investigated with respect to the release of ozone (O(3) ), volatile organic compounds (VOC), particulate matter (PM), and submicrometer particles (SMP) during standby and operation. Experiments were conducted in a 1 m(3) emission chamber connected to a Vitrocell(r) exposure system. Cytotoxicity was determined by the WST-1 assay and genotoxicity by the micronucleus test in human A549 lung cells. The five laser printers emitted varying but generally small amounts of O(3) , VOC, and PM. VOC emissions included 13 compounds with total VOC concentrations ranging from 95 to 280 MUg/m(3) (e.g., 2-butanone, hexanal, m,p-xylene, and o-xylene). Mean PM concentrations were below 2.4 MUg/m(3). SMP number concentration levels during standby ranged from 9 to 26 particles/cm(3). However, three of the printers generated a 90 to 16 * 10(3) fold increase of SMP during the printing process (maximum 294,460 particles/cm(3)). Whereas none of the printer emissions were found to cause cytotoxicity, emissions from two printers induced formation of micronuclei (P < 0.001), thus providing evidence for genotoxicity. As yet, differences in biological activity cannot be explained on the basis of the specific emission characteristics of the different printers. Because laser printing technology is widely used, studies with additional cytogenetic endpoints are necessary to confirm the DNA-damaging potency and to identify emission components responsible for genotoxicity. PMID- 22069141 TI - Reducing the influence of b-value selection on diffusion-weighted imaging of the prostate: evaluation of a revised monoexponential model within a clinical setting. AB - PURPOSE: To compare the accuracy of standard and revised monoexponential models of diffusion-weighted magnetic resonance imaging (DW-MRI) data for differentiating malignant from benign prostate tissue, using surgical pathology as the reference standard. MATERIALS AND METHODS: The Institutional Review Board waived informed consent for this Health Insurance Portability and Accountability Act (HIPAA)-compliant, retrospective study of 46 patients (median age = 61 years; range: 42-85 years) who underwent DW-MRI between May and December 2008 before radical prostatectomy for biopsy-proven prostate cancer, had no prior treatment, and had whole-mount step-section pathology maps available showing at least one peripheral zone (PZ) lesion >0.1 cm(3) . DW-MRI data were obtained for b-values of 0, 400, and 700 s/mm(2) . Apparent diffusion coefficients (ADCs) were estimated from PZ regions of interest (ROIs) on b = 0, 700 and b = 0, 400 s/mm(2) images, using a standard monoexponential model. The true diffusion coefficient (D) and perfusion fraction (f) were measured using a revised monoexponential model incorporating all three b-values. Areas under receiver operating characteristic curves (AUCs) were calculated to assess the accuracy of individual parameters and a logistic regression model combining D and f (D+f) in distinguishing malignant ROIs; P < 0.05 denoted significance. RESULTS: ADC(400) (AUC = 0.81, P < 0.0001), ADC(700) (AUC = 0.79, P < 0.0001), D (AUC = 0.71, P = 0.0001) and D + f distinguished malignant from benign ROIs (AUC = 0.82, P < 0.0001), but f did not (AUC = 0.56, P = 0.28); D + f was significantly more accurate than D (P = 0.016) but not more accurate than ADC(400) (P = 0.26) or ADC(700) (P = 0.12). CONCLUSION: The true diffusion coefficient provides an additional DW-MRI parameter for distinguishing prostate cancer that is less influenced than the ADC by b-value selection. PMID- 22069142 TI - Neurocognitive outcome in patients with hypertyrosinemia type I after long-term treatment with NTBC. AB - OBJECTIVE: The implementation of NTBC into treatment of hypertyrosinemia type I (HT I) greatly improved survival by prevention of acute liver failure and hepatocellular carcinoma. However, there are first reports of cognitive impairment in patients with elevated plasma tyrosine concentrations. METHODS: We here assess the neurocognitive development using standardized psychometric test batteries with respect to cognition, motor abilities and speech in nine early treated patients with HT I under long-term NTBC treatment. RESULTS: High plasma tyrosine concentrations were frequently documented resulting in elevated 12-month median plasma tyrosine concentrations in seven out of nine patients. Plasma NTBC concentrations were generally in the lower therapeutic range. Five out of seven patients (71%) above 3 years of age had a total IQ score below the average. In addition, five out of seven patients above 3 years showed an inhomogenous test profile with significant differences between the different testing scales. Motor abilities were subnormal in four out of seven patients(57%). Cerebral MRI revealed no abnormalities. Logopedic evaluation in children at school age documented dysfunction or retardation in language development in all but one of the tested patients (80%), however, all but one patients had a migration background. CONCLUSIONS: A high number of patients performed below normal in the assessment of development, motor function and speech. We propose intellectual impairment as long-term complication in HT type I with elevated plasma tyrosine under NTBC treatment as observed in other hypertyrosinemias. These findings remain to be reproduced in greater patient numbers. PMID- 22069143 TI - Cystathionine beta-synthase mutants exhibit changes in protein unfolding: conformational analysis of misfolded variants in crude cell extracts. AB - Protein misfolding has been proposed to be a common pathogenic mechanism in many inborn errors of metabolism including cystathionine beta-synthase (CBS) deficiency. In this work, we describe the structural properties of nine CBS mutants that represent a common molecular pathology in the CBS gene. Using thermolysin in two proteolytic techniques, we examined conformation of these mutants directly in crude cell extracts after expression in E. coli. Proteolysis with thermolysin under native conditions appeared to be a useful technique even for very unstable mutant proteins, whereas pulse proteolysis in a urea gradient had limited values for the study of the majority of CBS mutants due to their instability. Mutants in the active core had either slightly increased unfolding (p.A114V, p.E302K and p.G307S) or extensive unfolding with decreased stability (p.H65R, p.T191M, p.I278T and p.R369C). The extent of the unfolding inversely correlated with the previously determined degree of tetrameric assembly and with the catalytic activity. In contrast, mutants bearing aminoacid substitutions in the C-terminal regulatory domain (p.R439Q and p.D444N) had increased global stability with decreased flexibility. This study shows that proteolytic techniques can reveal conformational abnormalities even for CBS mutants that have activity and/or a degree of assembly similar to the wild-type enzyme. We present here a methodological strategy that may be used in cell lysates to evaluate properties of proteins that tend to misfold and aggregate and that may be important for conformational studies of disease-causing mutations in the field of inborn errors of metabolism. PMID- 22069144 TI - On the interpretation of removable interactions: a survey of the field 33 years after Loftus. AB - In a classic 1978 Memory & Cognition article, Geoff Loftus explained why noncrossover interactions are removable. These removable interactions are tied to the scale of measurement for the dependent variable and therefore do not allow unambiguous conclusions about latent psychological processes. In the present article, we present concrete examples of how this insight helps prevent experimental psychologists from drawing incorrect conclusions about the effects of forgetting and aging. In addition, we extend the Loftus classification scheme for interactions to include those on the cusp between removable and nonremovable. Finally, we use various methods (i.e., a study of citation histories, a questionnaire for psychology students and faculty members, an analysis of statistical textbooks, and a review of articles published in the 2008 issue of Psychology and Aging) to show that experimental psychologists have remained generally unaware of the concept of removable interactions. We conclude that there is more to interactions in a 2 * 2 design than meets the eye. PMID- 22069145 TI - Contrast class cues and performance facilitation in a hypothesis-testing task: evidence for an iterative counterfactual model. AB - Hypothesis-testing performance on Wason's (Quarterly Journal of Experimental Psychology 12:129-140, 1960) 2-4-6 task is typically poor, with only around 20% of participants announcing the to-be-discovered "ascending numbers" rule on their first attempt. Enhanced solution rates can, however, readily be observed with dual-goal (DG) task variants requiring the discovery of two complementary rules, one labeled "DAX" (the standard "ascending numbers" rule) and the other labeled "MED" ("any other number triples"). Two DG experiments are reported in which we manipulated the usefulness of a presented MED exemplar, where usefulness denotes cues that can establish a helpful "contrast class" that can stand in opposition to the presented 2-4-6 DAX exemplar. The usefulness of MED exemplars had a striking facilitatory effect on DAX rule discovery, which supports the importance of contrast-class information in hypothesis testing. A third experiment ruled out the possibility that the useful MED triple seeded the correct rule from the outset and obviated any need for hypothesis testing. We propose that an extension of Oaksford and Chater's (European Journal of Cognitive Psychology 6:149-169, 1994) iterative counterfactual model can neatly capture the mechanisms by which DG facilitation arises. PMID- 22069146 TI - Submicroscopic deletion of 12q13 including HOXC gene cluster with skeletal anomalies and global developmental delay. AB - We report on a patient with a submicroscopic deletion of 12q13 detected by array CGH and confirmed by FISH. He was haploinsufficient for the HOXC gene cluster and some other neighboring genes. HOX genes have an important role in the initial formation of the body. The patient showed characteristic features including severe kyphoscoliosis, digital abnormalities, cardiac anomaly, expressive language, and global developmental delay. Radiologic features of the fingers had some similarities with those for multiple synostosis syndrome. No human genetic disorders due to HOXC abnormalities are yet known. We tentatively assume that his skeletal anomalies are associated with haploinsufficiency of the HOXC gene cluster. Further studies are necessary to determine the clinical importance of haploinsufficiency of the HOXC gene cluster. PMID- 22069147 TI - New azidotetrazoles: structurally interesting and extremely sensitive. AB - The treatment of triaminoguanidinium chloride with two equivalents of sodium nitrite under acidic conditions, followed by the cyclization with stoichiometric amounts of either sodium hydroxide solution or solid sodium carbonate yielded 1 amino-5-azidotetrazole (1), 5-azido-1-diazidocarbamoyltetrazole (2), and 1 (aminoazidocarbamoyl)-5-azidotetrazole (3). The three novel compounds could be isolated by short-column liquid chromatography by using chloroform in reasonable yields. The mechanism of the formation as well as the decomposition pathway of the materials was investigated and a full characterization of all three compounds is presented. Compounds 1-3 have been characterized by means of Raman and IR as well as multinuclear NMR spectroscopy, mass spectrometry, and X-ray diffraction studies. Thermal stabilities have been evaluated by differential scanning calorimetry. Theoretical calculations have been performed to ensure the assignment of the vibrational modes obtained from Raman and IR measurements. The sensitivity values obtained from our measurements reflect the behavior of the compounds, which show an extremely high sensitivity toward mechanical as well as thermal stimuli. PMID- 22069148 TI - Physical evidence of child sexual abuse. AB - Child sexual abuse is increasingly recognised in all societies, affecting boys and girls alike in all age groups and often involving oral, anal and vaginal penetration. The presence of physical evidence following suspected child sexual abuse is important in confirming the diagnosis and providing legal corroboration that abuse has occurred. Whilst many children have no physical evidence, its presence should be carefully sought and documented by skilled examination, regardless of the time interval between any suspected abuse and the examination. When examination is close to the time of the abuse, forensic sampling may be required. Although many children have no physical findings, understanding the significance of physical findings has increased with both experience and research, although certainty and agreement is lacking in some areas. There are few case control studies of abused and non-abused children where standard terminology, examination method and description allow for meaningful comparison. CONCLUSIONS: Physical findings rarely provide conclusive evidence of sexual abuse in isolation but may offer important pieces of the diagnostic "jigsaw picture". PMID- 22069149 TI - Lewis acid-promoted synthesis of unsymmetrical and highly functionalized carbazoles and dibenzofurans from biaryl triazenes: application for the total synthesis of clausine C, clausine R, and clauraila A. PMID- 22069150 TI - Proteins influencing foam formation in wine and beer: the role of yeast. AB - This review focuses on the role of proteins in the production and maintenance of foam in both sparkling wines and beer. The quality of the foam in beer but especially in sparkling wines depends, among other factors, on the presence of mannoproteins released from the yeast cell walls during autolysis. These proteins are hydrophobic, highly glycosylated, and their molecular masses range from 10 to 200 kDa--characteristics that allow mannoproteins to surround and thus stabilize the gas bubbles of the foam. Both the production and stabilization of foam also depend on other proteins. In wine, these include grape-derived proteins such as vacuolar invertase; in beer, barley-derived proteins, such as LTP1, protein Z, and hordein-derived polypeptides, are even more important in this respect than mannoproteins. PMID- 22069151 TI - Electricity generation by microorganisms in the sediment-water interface of an extreme acidic microcosm. AB - The attachment of microorganisms to electrodes is of great interest for electricity generation in microbial fuel cells (MFC) or other applications in bioelectrochemical systems (BES). In this work, a microcosm of the acidic ecosystem of Rio Tinto was built and graphite electrodes were introduced at different points. This allowed the study of electricity generation in the sediment/water interface and the involvement of acidophilic microorganisms as biocatalysts of the anodic and cathodic reactions in a fuel-cell configuration. Current densities and power outputs of up to 3.5 A/m2 and 0.3 W/m2, respectively, were measured at pH 3. Microbial analyses of the electrode surfaces showed that Acidiphilium spp., which uses organic compounds as electron donors, were the predominant biocatalysts of the anodic reactions, whereas the aerobic iron oxidizers Acidithiobacillus ferrooxidans and Leptospirillum spp. were detected mainly on the cathode surface. PMID- 22069152 TI - Comparison of the gut microbiota from soldier and worker castes of the termite Reticulitermes grassei. AB - The bacterial microbiota from the whole gut of soldier and worker castes of the termite Reticulitermes grassei was isolated and studied. In addition, the 16S rDNA bacterial genes from gut DNA were PCR-amplified using Bacteria-selective primers, and the 16S rDNA amplicons subsequently cloned into Escherichia coli. Sequences of the cloned inserts were then used to determine closest relatives by comparison with published sequences and with sequences from our previous work. The clones were found to be affiliated with the phyla Spirochaetes, Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Synergistetes, Verrucomicrobia, and candidate phyla Termite Group 1 (TG1) and Termite Group 2 (TG2). No significant differences were observed with respect to the relative bacterial abundances between soldier and worker phylotypes. The phylotypes obtained in this study were compared with reported sequences from other termites, especially those of phylotypes related to Spirochaetes, Wolbachia (an Alphaproteobacteria), Actinobacteria, and TG1. Many of the clone phylotypes detected in soldiers grouped with those of workers. Moreover, clones CRgS91 (soldiers) and CRgW68 (workers), both affiliated with 'Endomicrobia', were the same phylotype. Soldiers and workers also seemed to have similar relative protist abundances. Heterotrophic, poly-beta-hydroxyalkanoate-accumulating bacteria were isolated from the gut of soldiers and shown to be affiliated with Actinobacteria and Gammaproteobacteria. We noted that Wolbachia was detected in soldiers but not in workers. Overall, the maintenance by soldiers and workers of comparable axial and radial redox gradients in the gut is consistent with the similarities in the prokaryotes and protists comprising their microbiota. PMID- 22069153 TI - Screening and evaluation of antiparasitic and in vitro anticancer activities of Panamanian endophytic fungi. AB - Many compounds produced by fungi have relevant pharmaceutical applications. The purpose of this study was to collect and isolate endophytic fungi from different regions of Panama and then to test their potential therapeutic activities against Leishmania donovani, Plasmodium falciparum, and Trypanosoma cruzi as well as their anticancer activities in MCF-7 cells. Of the 25 fungal isolates obtained, ten of them had good anti-parasitic potential, showing selective activity against L. donovani; four had significant anti-malarial activity; and three inhibited the growth of T. cruzi. Anticancer activity was demonstrated in four isolates. Of the active isolates, Edenia sp. strain F0755, Xylaria sp. strain F1220, Aspergillus sp. strain F1544, Mycoleptodiscus sp. strain F0194, Phomopsis sp. strain F1566, Pycnoporus sp. strain F0305, and Diaporthe sp. strain F1647 showed the most promise based on their selective bioactivity and lack of toxicity in the assays. PMID- 22069154 TI - Identification of lactobacilli residing in chicken ceca with antagonism against Campylobacter. AB - Bacteriocins produced by Lactobacillus salivarius have been recently recognized as a natural means to control Campylobacter and Salmonella in live poultry. This finding is of relevance since Campylobacter jejuni and Campylobacter coli are the predominant species isolated from poultry that are associated with human campylobacteriosis. In the present work, lactic acid bacteria (LAB) isolated from the cecum of twenty Tunisian chickens were identified and those isolates with antagonism against Campylobacter were further characterized. Following their preliminary confirmation as LAB, 150 strains were identified by combining morphological criteria, biochemical tests, and molecular methods, the latter inluding intergenic 16S- 23S PCR, specific lactobacilli PCR, and a biphasic approach. Most of the LAB isolated belonged to the genus Lactobacillus, among them Lb. sakei (33.3%), Lb. salivarius (19.4%), Lb. reuteri (8.6%), and Lb. curvatus (8.6%). The other LAB strains included those of the genus Weissella (16.7%), Enterococcus faecalis (5.3%), Leuconostoc mesenteroides (2.7%), Lactococcus graviae (2.7%), and Streptococcus sp. (2.7%). The Lactobacilli strains were tested for their antagonism against C. jejuni and C. coli. The activity of three of them, Lb. salivarius SMXD51, Lb. salivarius MMS122, and Lb. salivarius MMS151, against the aforementioned target strains could be ascribed to the production of bacteriocins. PMID- 22069155 TI - Genomics and transcriptomics characterization of genes expressed during postharvest at 4 degrees C by the edible basidiomycete Pleurotus ostreatus. AB - Pleurotus ostreatus is an industrially cultivated basidiomycete with nutritional and environmental applications. Its genome, which was sequenced by the Joint Genome Institute, has become a model for lignin degradation and for fungal genomics and transcriptomics studies. The complete P. ostreatus genome contains 35 Mbp organized in 11 chromosomes, and two different haploid genomes have been individually sequenced. In this work, genomics and transcriptomics approaches were employed in the study of P. ostreatus under different physiological conditions. Specifically, we analyzed a collection of expressed sequence tags (EST) obtained from cut fruit bodies that had been stored at 4 degrees C for 7 days (postharvest conditions). Studies of the 253 expressed clones that had been automatically and manually annotated provided a detailed picture of the life characteristics of the self-sustained fruit bodies. The results suggested a complex metabolism in which autophagy, RNA metabolism, and protein and carbohydrate turnover are increased. Genes involved in environment sensing and morphogenesis were expressed under these conditions. The data improve our understanding of the decay process in postharvest mushrooms and highlight the use of high-throughput techniques to construct models of living organisms subjected to different environmental conditions. PMID- 22069156 TI - Spinal subdural hemorrhage in abusive head trauma: a retrospective study. AB - PURPOSE: To compare the relative incidence, distribution, and radiologic characteristics of spinal subdural hemorrhage after abusive head trauma versus that after accidental trauma in children. MATERIALS AND METHODS: This study received prior approval from the Human Subjects Protection Office. Informed consent was waived. This study was HIPAA compliant. Two hundred fifty-two children aged 0-2 years treated for abusive head trauma at our institute between 1997 and 2009 were identified through retrospective chart review. A second group of 70 children aged 0-2 years treated at our institute for well-documented accidental trauma between 2003 and 2010 were also identified through retrospective chart review. All clinical data and cross-sectional imaging results, including computed tomographic and magnetic resonance imaging of the brain, spine, chest, abdomen, and pelvis, were reviewed for both of these groups. A Fisher exact test was performed to assess the statistical significance of the proportion of the spinal canal subdural hemorrhage in abusive head trauma versus that in accidental trauma. RESULTS: In the abusive head trauma cohort, 67 (26.5%) of 252 children had evaluable spinal imaging results. Of these, 38 (56%) of 67 children had undergone thoracolumbar imaging, and 24 (63%) of 38 had thoracolumbar subdural hemorrhage. Spinal imaging was performed in this cohort 0.3-141 hours after injury (mean, 23 hours +/- 27 [standard deviation]), with 65 (97%) of 67 cases having undergone imaging within 52 hours of injury. In the second cohort with accidental injury, only one (1%) of 70 children had spinal subdural hemorrhage at presentation; this patient had displaced occipital fracture. The comparison of incidences of spinal subdural hemorrhage in abusive head trauma versus those in accidental trauma was statistically significant (P < .001). CONCLUSION: Spinal canal subdural hemorrhage was present in more than 60% of children with abusive head trauma who underwent thoracolumbar imaging in this series but was rare in those with accidental trauma. PMID- 22069159 TI - Prevalence of musculoskeletal disorders among farmers: A systematic review. AB - OBJECTIVE: To determine the prevalence of musculoskeletal disorders (MSDs) among farmers and to establish the most common regional MSDs reported. METHODS: Comprehensive electronic searches of Pubmed, Web of Science, CINAHL, SCOPUS, EMBASE, Agris Database, and Cochrane Library were carried out using keywords for MSDs and farmers. Pooled estimates of prevalence with 95% confidence intervals were calculated for overall MSD prevalence and the most common regional MSDs reported. RESULTS: Twenty-four studies fulfilled the inclusion criteria and were incorporated into this review. From these studies, life-time prevalence of any form of MSD among farmers was 90.6% while 1-year MSD prevalence was 76.9% (95% CI 69.8-82.7). The majority of studies focused on spinal MSDs with low back pain (LBP) the most frequently investigated. Life-time LBP prevalence was 75% (95% CI 67-81.5) while 1-year LBP prevalence was 47.8% (95% CI 40.2-55.5). The next most common regional MSDs reported were upper (range 3.6-71.4%) and lower extremities (range 10.4-41%). CONCLUSIONS: The systematic review identified the prevalence of MSDs by body region in farmers and established that LBP was the most common MSD, followed by upper and then lower extremity MSDs. Reported trends suggest that the prevalence of MSDs in farmers is greater than in non-farmer populations. Case definition uniformity among MSD researchers is warranted. More studies are needed regarding upper and lower extremity MSDs, gender, workplace, and task context of MSDs. PMID- 22069161 TI - Dye-terminated, hyperbranched polytruxenes and polytruxene-block-polythiophene multiblock copolymers made in an "AB2 + A" approach. AB - Novel dye-terminated, hyperbranched polytruxenes and polytruxene-block polythiophene multiblock copolymers have been synthesized in a simple "AB(2) + A" approach. Photoexcitation into the higher energy polytruxene absorption band results in an efficient excitation energy transfer to the peripheral dye or polythiophene blocks. PMID- 22069160 TI - Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer. AB - Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol(r)) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict paclitaxel responses in women presenting with high-grade serous EOC. PMID- 22069162 TI - Variation of noise in multi-run functional MRI using generalized autocalibrating partially parallel acquisition (GRAPPA). AB - PURPOSE: To investigate the noise variation in multi-run functional MRI (fMRI) scans using generalized autocalibrating partially parallel acquisition (GRAPPA), with a focus on the cause of this variation. MATERIALS AND METHODS: A phantom was continuously scanned for 10 runs using echo-planar imaging (EPI) combined with GRAPPA to simulate a multi-run fMRI exam. The variation of noise between runs was examined for different GRAPPA acceleration factors. The noise variation was also evaluated in a real fMRI experiment with human subjects at an acceleration factor of two. The cause of noise variation was explored by offline reconstruction using different GRAPPA weights and numerical simulation of GRAPPA reference scans. RESULTS: It was found that the noise distribution in the image is stable within a run but may vary randomly from run to run. The variation of noise was also observed in fMRI experiments with human subjects. The variation can be significantly reduced if all the images from individual runs are reconstructed using the same reference scan data. CONCLUSION: Both phantom experiments and human data showed that the noise pattern may change in different fMRI runs. The variation is mainly caused by the random noise in separate reference scans for GRAPPA in each run. PMID- 22069163 TI - Hydrolysis of ammonia borane as a hydrogen source: fundamental issues and potential solutions towards implementation. AB - In today's era of energy crisis and global warming, hydrogen has been projected as a sustainable alternative to depleting CO(2)-emitting fossil fuels. However, its deployment as an energy source is impeded by many issues, one of the most important being storage. Chemical hydrogen storage materials, in particular B-N compounds such as ammonia borane, with a potential storage capacity of 19.6 wt % H(2) and 0.145 kg(H2)L(-1), have been intensively studied from the standpoint of addressing the storage issues. Ammonia borane undergoes dehydrogenation through hydrolysis at room temperature in the presence of a catalyst, but its practical implementation is hindered by several problems affecting all of the chemical compounds in the reaction scheme, including ammonia borane, water, borate byproducts, and hydrogen. In this Minireview, we exhaustively survey the state of the art, discuss the fundamental problems, and, where applicable, propose solutions with the prospect of technological applications. PMID- 22069165 TI - Enantioselective syntheses of corynanthe alkaloids by chiral Bronsted acid and palladium catalysis. PMID- 22069164 TI - Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature. AB - To identify causes of death (COD) in propositi with Cornelia de Lange syndrome (CdLS) at various ages, and to develop guidelines to improve management and avoid morbidity and mortality, we retrospectively reviewed a total of 426 propositi with confirmed clinical diagnoses of CdLS in our database who died in a 41-year period between 1966 and 2007. Of these, 295 had an identifiable COD reported to us. Clinical, laboratory, and complete autopsy data were completed on 41, of which 38 were obtainable, an additional 19 had autopsies that only documented the COD, and 45 propositi had surgical, imaging, or terminal event clinical documentation of their COD. Proband ages ranged from fetuses (21-40 weeks gestation) to 61 years. A literature review was undertaken to identify all reported causes of death in CdLS individuals. In our cohort of 295 propositi with a known COD, respiratory causes including aspiration/reflux and pneumonias were the most common primary causes (31%), followed by gastrointestinal disease, including obstruction/volvulus (19%). Congenital anomalies accounted for 15% of deaths and included congenital diaphragmatic hernia and congenital heart defects. Acquired cardiac disease accounted for 3% of deaths. Neurological causes and accidents each accounted for 8%, sepsis for 4%, cancer for 2%, renal disease for 1.7%, and other causes, 9% of deaths. We also present 21 representative clinical cases for illustration. This comprehensive review has identified important etiologies contributing to the morbidity and mortality in this population that will provide for an improved understanding of clinical complications, and management for children and adults with CdLS. PMID- 22069166 TI - Normative data for anthropometric parameters used in delineation of dysmorphic features in north Indian children. AB - OBJECTIVE: To provide normative data for a set of anthropometric parameters which are commonly used in delineation of dysmorphic features. METHODS: This cross sectional observational study was conducted in a tertiary care hospital of Delhi. Six hundred infants and children up to 2 years with hundred subjects each in the age group of 0-3, 3-6, 6-9, 9-12, 12-18 and 18-24 months were included. Both sexes were represented equally in the sample to avoid bias. Inner and outer intercanthal distance were measured by sliding callipers. Inter pupillary distance was measured directly as the distance between midpoint of two pupils. Ear length was the maximum vertical distance from the superior to the inferior edge of the ear. Internipple distance was the distance between centre of both nipples. Hand length was the distance between distal wrist crease to the tip of middle finger. Middle finger length was the distance between proximal flexion crease and tip of middle finger. The data was analyzed using the LMS method and percentile curves were developed for each age group for all the seven parameters. RESULTS: No statistically significant differences between male and female infants were observed. Significant differences were observed from other south east Asian and Caucasian population stressing the need for generation of regional ethnic data. The percentage of other isolated anomalies noted was 1.16% for polydactyly, 2-4 syndactyly 2-4 toe syndactyly (0.89%), Preauricular tags (0.5%), double whorl pattern of hair (1.55%), 2-4 syndactyly (0.33%) and paraumbilical hernia (2.83%). CONCLUSIONS: Normative data directed towards the ethnic origin are useful in charting dysmorphic traits. Children with parameters less than 3rd percentile or more than 97th percentile should be evaluated for other co-existing anomalies. Percentile charts provided in the present study may also be applicable across India but more studies are required to validate the authors' contention. PMID- 22069168 TI - Capillarity creates single-crystal calcite nanowires from amorphous calcium carbonate. AB - Single-crystal calcite nanowires are formed by crystallization of morphologically equivalent amorphous calcium carbonate (ACC) particles within the pores of track etch membranes. The polyaspartic acid stabilized ACC is drawn into the membrane pores by capillary action, and the single-crystal nature of the nanowires is attributed to the limited contact of the intramembrane ACC particle with the bulk solution. The reaction environment then supports transformation to a single crystal product. PMID- 22069167 TI - Access to health services and early age mortality in Ende, Indonesia. AB - OBJECTIVE: Improvements in child survival to achieve Millennium Development Goal 4 require highly accessible and effective maternal and child health (MCH) services. This article seeks to fill the gap in information for local government in Indonesia about early age mortality and access to appropriate care to inform the evaluation and planning of MCH services. METHODS: The Ende Child Mortality Survey (ECMS) was conducted in the district of Ende in Nusa Tenggara Timur (NTT), one of the poorest provinces in Indonesia. The ECMS is a cross-sectional household survey, providing information on child survival, MCH service utilisation, and socio-economic characteristics of the population. Multivariate logistic regression was conducted to examine the association of mortality, health service utilisation and socio-economic variables. RESULTS: Use of an unskilled birth attendant (45% of births) and giving birth at home are most common among the poorest and least educated women. The children of these women have the highest risk of infant mortality. The infant mortality rate differs greatly by region within Ende. Time to the preferred provider of child health care is longest in regions with the highest under-five mortality risk. CONCLUSIONS: Many women in Ende do not receive vital interventions during labour to reduce infant mortality. The ECMS demonstrates the feasibility in implementing a low cost survey to provide evidence for MCH investments to improve accessibility to appropriate health services and reduce mortality risk. PMID- 22069169 TI - Towards power and sample size calculations for the comparison of two groups of patients with item response theory models. AB - Evaluation of patient-reported outcomes (PRO) is increasingly performed in health sciences. PRO differs from other measurements because such patient characteristics cannot be directly observed. Item response theory (IRT) is an attractive way for PRO analysis. However, in the framework of IRT, sample size justification is rarely provided or ignores the fact that PRO measures are latent variables with the use of formulas developed for observed variables. It might therefore be inappropriate and might provide inadequately sized studies. The objective was to develop valid sample size methodology for the comparison of PRO in two groups of patients using IRT. The proposed approach takes into account questionnaire's items parameters, the difference of the latent variables means, and its variance whose derivation is approximated using Cramer-Rao bound (CRB). We also computed the associated power. We realized a simulation study taking into account sample size, number of items, and value of the group effect. We compared power obtained from CRB with the one obtained from simulations (SIM) and with the power based on observed variables (OBS). For a given sample size, powers using CRB and SIM were similar and always lower than OBS. We observed a strong impact of the number of items for CRB and SIM, the power increasing with the questionnaire's length but not for OBS. In the context of latent variables, it seems important to use an adapted sample size formula because the formula developed for observed variables seems to be inadequate and leads to an underestimated study size. PMID- 22069170 TI - Tribute to Alfred E. Chang. PMID- 22069171 TI - Histopathology of gastrointestinal stromal tumor. AB - Gastrointestinal stromal tumor (GIST), generally driven by oncogenic KIT or PDGFRA mutations, is the most common mesenchymal tumor of the gastrointestinal (GI) tract. GIST is most common in the stomach (60%) and small intestine (30%), but can occur anywhere in the GI-tract and the intra-abdominal soft tissues. GIST can show spindle cell or epithelioid morphology, and mitotic count and tumor size are most important prognostic parameters. GISTs in NF1 patients and children are distinctive clinicopathologic groups. Immunohistochemical testing for KIT and sometimes for DOG1/Ano 1 is essential in confirming the diagnosis. PMID- 22069172 TI - Morphology of gastrointestinal stromal tumors: historical perspectives. AB - About 2/3 of gastrointestinal stromal tumors occur in the stomach and about 1/5 in the small intestine with few in the rectum, colon, and esophagus. Their cells are related to the interstitial cells of Cajal. They differ by site in terms of cell type and growth pattern. Benign and malignant tumors are separated based on their light microscopic appearances, size as measured by innumerable pathologists and assistants and mitotic counts. PMID- 22069173 TI - Advanced or metastatic gastrointestinal stromal tumors: systemic treatment options. AB - Gastrointestinal stromal tumor (GIST), the most common sarcoma arising in the gastrointestinal tract, typically expresses the tyrosine-kinase receptor, C-KIT, and contains activating mutation in the c-kit or platelet-derived growth factor receptor (pdgfr) gene. Recently, development of small molecules that inhibit the kinase activity of mutant C-KIT and PDGFR proteins has radically changed treatment and prognosis of patients diagnosed with advanced GIST as this molecularly "targeted" therapy has demonstrated remarkable high-level of activity in this disease. PMID- 22069174 TI - Adjuvant imatinib therapy for gastrointestinal stromal tumors. AB - Surgery is the standard of care for primary resectable gastrointestinal stromal tumors (GISTs), but half of surgically treated patients relapse. Imatinib (IM) has been shown to prolong recurrence-free survival after complete surgery and is now approved as adjuvant therapy (400 mg/day) for high-risk GIST patients. IM is well tolerated, with mild to moderate side effects observed. Whether adjuvant IM prolongs overall survival is under evaluation in two ongoing clinical trials. PMID- 22069175 TI - Systemic therapy for advanced gastrointestinal stromal tumors: beyond imatinib. AB - Progression on first-line therapy with imatinib in gastrointestinal stromal tumors (GIST) is caused by either initial resistance or more often a secondary mutation in tyrosine kinases KIT or PDGFR. Therapies in development for imatinib resistant GIST include agents that target KIT/PDGFR with greater potency or possess broader kinase inhibition profiles including VEGFR. To circumvent secondary mutations in KIT/PDGFR, inhibition of the downstream signaling in PI3K/Akt/mTOR pathway and enhanced degradation of KIT/PDGFR are also under investigation. PMID- 22069176 TI - Imaging modalities of gastrointestinal stromal tumors. AB - Recent dramatic improvement of survival of Gastrointestinal stromal tumor patients alongside the development of a new targeted treatment has made the role of imaging increasingly more important not only in diagnosing the disease, but also in monitoring the treatment effect and surveillance. Computed tomography is currently the imaging modality of choice for these purposes. This article reviews the current roles of different imaging modalities in clinical management of the gastrointestinal stromal tumors. PMID- 22069177 TI - Surveillance strategies for gastrointestinal stromal tumors. AB - Although only 10-30% of gastrointestinal stromal tumors (GISTs) are clinically malignant, all have some degree of malignant potential. The management of high risk patients should be evidence based. However, prospective data and a consensus for guidelines concerning the screening of asymptomatic high risk patients and surveillance following multidisciplinary treatment do not exist. This review provides an overview of GIST, with an emphasis on the available data regarding screening and surveillance of certain populations with GISTs. PMID- 22069178 TI - Special considerations in pediatric gastrointestinal tumors. AB - Pediatric gastrointestinal tumors are rare in children but are being increasingly recognized. These tumors have distinct biologic and clinical feature that are different from those observed in adults. This review highlights the biological and clinical characteristics of pediatric GIST and provides diagnostic and therapeutic guidelines for the management these unique and challenging group of tumors. PMID- 22069179 TI - Photosensitized hydrogen evolution from water using a single-walled carbon nanotube/fullerodendron/SiO2 coaxial nanohybrid. AB - A coaxial nanohybrid consisting of a single-walled carbon nanotube (SWCNT), fullerodendron, and SiO(2) shows high-efficiency light-driven hydrogen evolution from water. Upon visible light irradiation, SWCNT/fullerodendron/SiO(2) coaxial nanohybrid shows hydrogen evolution activity in the presence of methyl viologen (MV(2+)), benzyldihydronicotinamide (BNAH), and a colloidal polyvinyl alcohol(PVA)-Pt. PMID- 22069180 TI - Guidelines for good database selection and use in pharmacoepidemiology research. AB - The use of healthcare databases in research provides advantages such as increased speed, lower costs and limitation of some biases. However, database research has its own challenges as studies must be performed within the limitations of resources, which often are the product of complex healthcare systems. The primary purpose of this document is to assist in the selection and use of data resources in pharmacoepidemiology, highlighting potential limitations and recommending tested procedures. This guidance is presented as a detailed text with a checklist for quick reference and covers six areas: selection of a database, use of multiple data resources, extraction and analysis of the study population, privacy and security, quality and validation procedures and documentation. PMID- 22069181 TI - Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp-Hodgkin/AEC/ADULT syndromes. AB - Heterozygous mutations in TP63 cause a wide spectrum of autosomal dominant developmental disorders variably affecting skin, limbs, and face. TP63 encodes p63, a protein expressed in two main isoforms (Tap63 and DeltaNp63) with critical roles in both cell differentiation and development. Some analyses suggest a relationship of the mutation site to the observed clinical picture, although this link is inconsistent. This suggests an appreciable phenotypic continuity within the TP63-related disorders. We report a 3-month-old boy ascertained for congenital scalp erosion and mild features of ectodermal dysplasia. His mother showed full-blown characteristics of Rapp-Hodgkin syndrome plus intense abdominal and popliteal freckling. Molecular investigation identified the novel TP63 mutation c.1697delG. We used a luciferase reporter assay to compare the effects on the p63 transactivation (TA) activity of c.1697delG with that of the p.Arg280Cys and p.Gln634X mutations, associated with ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome and isolated split hand/foot malformation, respectively. These results demonstrated complex behavior of c.1697delG in the TA of genes involved in epidermal differentiation and development and shed further light in the physiopathology of TP63-related disorders. PMID- 22069183 TI - Fifty years of X-inactivation research. AB - The third X-inactivation meeting 'Fifty years of X-inactivation research', which celebrated the fiftieth anniversary of Mary Lyon's formulation of the X inactivation hypothesis, was an EMBO workshop held in Oxford, UK, in July 2011. This conference brought together the usual suspects from the field, as well as younger researchers, to discuss recent advances in X-inactivation research. Here, we review the results presented at the meeting and highlight some of the exciting progress that has been made. We also discuss the future challenges for the field, which aim to further our understanding of the developmental regulation of X inactivation, the randomness (or skewing) of X inactivation, and the diverse strategies used by mammalian species to mediate X inactivation. PMID- 22069182 TI - Inhibitory activities of pancreatic lipase and phosphodiesterase from Korean medicinal plant extracts. AB - To find new pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) inhibitors from natural products, 61 medicinal plants from Korea were screened for their antilipase activity for prevention of obesity. Dried and powdered plants were extracted three times with EtOH and extracts were obtained by removal of the solvent in vacuo. Lipase activity was determined by measuring the hydrolysis of p-nitrophenyl butyrate to p-nitrophenol. Also, the inhibitory effect was measured on phosphodiesterase (PDE), another therapeutic target for obesity. Of the extracts tested, Sorbus commixta (stem, leaf) and Viscum album (whole plant) exhibited antilipase activity (with IC(50) values of 29.6 ug/mL and 33.3 ug/mL, respectively) and only anti-PDE activity (IC(50) values of 20.08 ug/mL and 35.15 ug/mL, respectively). PMID- 22069184 TI - Chromosome silencing mechanisms in X-chromosome inactivation: unknown unknowns. AB - Fifty years ago, Mary Lyon hypothesised that one of the two X chromosomes in female mammalian cells is inactivated at random during early embryogenesis and that the inactive X is then stably maintained through all subsequent cell divisions. Although Lyon's hypothesis is now widely regarded as fact, we should not forget that her conceptual leap met with considerable resistance from the scientific establishment at the time - a common response to new ideas. Taking this point as a theme, I discuss our current understanding of the molecular mechanism of chromosome silencing in X-chromosome inactivation and focus on topics where new findings are challenging the prevailing view. PMID- 22069185 TI - Hedgehog and retinoic acid signaling cooperate to promote motoneurogenesis in zebrafish. AB - The precise requirements of Hedgehog (Hh) pathway activity in vertebrate central nervous system development remain unclear, particularly in organisms with both maternally and zygotically derived signaling. Here we describe the motoneural phenotype of zebrafish that lack maternal and zygotic contributions of the Hh signaling transducer Smoothened (MZsmo mutants) and therefore are completely devoid of ligand-dependent pathway activation. Some functional primary motoneurons (PMNs) persist in the absence of Hh signaling, and we find that their induction requires both basal Gli transcription factor activity and retinoic acid (RA) signaling. We also provide evidence that RA pathway activation can modulate Gli function in a Hh ligand-independent manner. These findings support a model in which Hh and RA signaling cooperate to promote PMN cell fates in zebrafish. PMID- 22069186 TI - Roles of Hedgehog pathway components and retinoic acid signalling in specifying zebrafish ventral spinal cord neurons. AB - In mouse, Hedgehog (Hh) signalling is required for most ventral spinal neurons to form. Here, we analyse the spinal cord phenotype of zebrafish maternal-zygotic smoothened (MZsmo) mutants that completely lack Hh signalling. We find that most V3 domain cells and motoneurons are lost, whereas medial floorplate still develops normally and V2, V1 and V0v cells form in normal numbers. This phenotype resembles that of mice that lack both Hh signalling and Gli repressor activity. Ventral spinal cord progenitor domain transcription factors are not expressed at 24 hpf in zebrafish MZsmo mutants. However, pMN, p2 and p1 domain markers are expressed at early somitogenesis stages in these mutants. This suggests that Gli repressor activity does not extend into zebrafish ventral spinal cord at these stages, even in the absence of Hh signalling. Consistent with this, ectopic expression of Gli3R represses ventral progenitor domain expression at these early stages and knocking down Gli repressor activity rescues later expression. We investigated whether retinoic acid (RA) signalling specifies ventral spinal neurons in the absence of Hh signalling. The results suggest that RA is required for the correct number of many different spinal neurons to form. This is probably mediated, in part, by an effect on cell proliferation. However, V0v, V1 and V2 cells are still present, even in the absence of both Hh and RA signalling. We demonstrate that Gli1 has a Hh-independent role in specifying most of the remaining motoneurons and V3 domain cells in embryos that lack Hh signalling, but removal of Gli1 activity does not affect more dorsal neurons. PMID- 22069187 TI - The astrocyte-expressed integrin alphavbeta8 governs blood vessel sprouting in the developing retina. AB - The mouse retina is vascularized after birth when angiogenic blood vessels grow and sprout along a pre-formed latticework of astrocytes. How astrocyte-derived cues control patterns of blood vessel growth and sprouting, however, remains enigmatic. Here, we have used molecular genetic strategies in mice to demonstrate that alphavbeta8 integrin expressed in astrocytes is essential for neovascularization of the developing retina. Selective ablation of alphav or beta8 integrin gene expression in astrocytes leads to impaired blood vessel sprouting and intraretinal hemorrhage, particularly during formation of the secondary vascular plexus. These pathologies correlate, in part, with diminished alphavbeta8 integrin-mediated activation of extracellular matrix-bound latent transforming growth factor betas (TGFbetas) and defective TGFbeta signaling in vascular endothelial cells, but not astrocytes. Collectively, our data demonstrate that alphavbeta8 integrin is a component of a paracrine signaling axis that links astrocytes to blood vessels and is essential for proper regulation of retinal angiogenesis. PMID- 22069189 TI - Retinoic acid-dependent and -independent gene-regulatory pathways of Pitx3 in meso-diencephalic dopaminergic neurons. AB - Development of meso-diencephalic dopamine (mdDA) neurons requires the combined actions of the orphan nuclear receptor Nurr1 and the paired-like homeobox transcription factor Pitx3. Whereas all mdDA neurons require Nurr1 for expression of Th and survival, dependence on Pitx3 is displayed only by the mdDA subpopulation that will form the substantia nigra (SNc). Previously, we have demonstrated that Pitx3(-/-) embryos lack the expression of the retinoic acid (RA)-generating enzyme Ahd2, which is normally selectively expressed in the Pitx3 dependent DA neurons of the SNc. Restoring RA signaling in Pitx3(-/-) embryos revealed a selective dependence of SNc neurons on the presence of RA for differentiation into Th-positive neurons and maintenance throughout embryonic development. Whereas these data are suggestive of an important developmental role for RA in neurons of the SNc, it remained unclear whether other Nurr1 and Pitx3 target genes depend on RA signaling in a manner similar to Th. In the search for genes that were affected in Pitx3-deficient mdDA neurons and restored upon embryonic RA treatment, we provide evidence that Delta-like 1, D2R (Drd2) and Th are regulated by Pitx3 and RA signaling, which influences the mdDA terminal differentiated phenotype. Furthermore, we show that regulation of Ahd2-mediated RA signaling represents only one aspect of the Pitx3 downstream cascade, as Vmat2, Dat, Ahd2 (Aldh1a1), En1, En2 and Cck were unaffected by RA treatment and are (subset) specifically modulated by Pitx3. In conclusion, our data reveal several RA-dependent and -independent aspects of the Pitx3-regulated gene cascade, suggesting that Pitx3 acts on multiple levels in the molecular subset specification of mdDA neurons. PMID- 22069188 TI - Regulation of Drosophila glial cell proliferation by Merlin-Hippo signaling. AB - Glia perform diverse and essential roles in the nervous system, but the mechanisms that regulate glial cell numbers are not well understood. Here, we identify and characterize a requirement for the Hippo pathway and its transcriptional co-activator Yorkie in controlling Drosophila glial proliferation. We find that Yorkie is both necessary for normal glial cell numbers and, when activated, sufficient to drive glial over-proliferation. Yorkie activity in glial cells is controlled by a Merlin-Hippo signaling pathway, whereas the upstream Hippo pathway regulators Fat, Expanded, Crumbs and Lethal giant larvae have no detectable role. We extend functional characterization of Merlin-Hippo signaling by showing that Merlin and Hippo can be physically linked by the Salvador tumor suppressor. Yorkie promotes expression of the microRNA gene bantam in glia, and bantam promotes expression of Myc, which is required for Yorkie and bantam-induced glial proliferation. Our results provide new insights into the control of glial growth, and establish glia as a model for Merlin specific Hippo signaling. Moreover, as several of the genes we studied have been linked to human gliomas, our results suggest that this linkage could reflect their organization into a conserved pathway for the control of glial cell proliferation. PMID- 22069190 TI - Reelin sets the pace of neocortical neurogenesis. AB - Migration of neurons during cortical development is often assumed to rely on purely post-proliferative reelin signaling. However, Notch signaling, long known to regulate neural precursor formation and maintenance, is required for the effects of reelin on neuronal migration. Here, we show that reelin gain-of function causes a higher expression of Notch target genes in radial glia and accelerates the production of both neurons and intermediate progenitor cells. Converse alterations correlate with reelin loss-of-function, consistent with reelin controlling Notch signaling during neurogenesis. Ectopic expression of reelin in isolated clones of progenitors causes a severe reduction in neuronal differentiation. In mosaic cell cultures, reelin-primed progenitor cells respond to wild-type cells by further decreasing neuronal differentiation, consistent with an increased sensitivity to lateral inhibition. These results indicate that reelin and Notch signaling cooperate to set the pace of neocortical neurogenesis, a prerequisite for proper neuronal migration and cortical layering. PMID- 22069191 TI - Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo. AB - Mastermind (Mam) is one of the elements of Notch signaling, a system that plays a pivotal role in metazoan development. Mam proteins form transcriptionally activating complexes with the intracellular domains of Notch, which are generated in response to the ligand-receptor interaction, and CSL DNA-binding proteins. In mammals, three structurally divergent Mam isoforms (MamL1, MamL2 and MamL3) have been identified. There have also been indications that Mam interacts functionally with various other transcription factors, including the p53 tumor suppressor, beta-catenin and NF-kappaB. We have demonstrated previously that disruption of MamL1 causes partial deficiency of Notch signaling in vivo. However, MamL1 deficient mice did not recapitulate total loss of Notch signaling, suggesting that other members could compensate for the loss or that Notch signaling could proceed in the absence of Mam in certain contexts. Here, we report the generation of lines of mice null for MamL3. Although MamL3-null mice showed no apparent abnormalities, mice null for both MamL1 and MamL3 died during the early organogenic period with classic pan-Notch defects. Furthermore, expression of the lunatic fringe gene, which is strictly controlled by Notch signaling in the posterior presomitic mesoderm, was undetectable in this tissue of the double-null embryos. Neither of the single-null embryos exhibited any of these phenotypes. These various roles of the three Mam proteins could be due to their differential physical characteristics and/or their spatiotemporal distributions. These results indicate that engagement of Mam is essential for Notch signaling, and that the three Mam isoforms have distinct roles in vivo. PMID- 22069192 TI - ID4 regulates mammary gland development by suppressing p38MAPK activity. AB - The ID family of helix-loop-helix proteins regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown. We report that mouse Id4 is expressed in cap cells, basal cells and in a subset of luminal epithelial cells, and that its targeted deletion impairs ductal expansion and branching morphogenesis as well as cell proliferation induced by estrogen and/or progesterone. We discover that p38MAPK is activated in Id4-null mammary cells. p38MAPK is also activated following siRNA-mediated Id4 knockdown in transformed mammary cells. This p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Therefore, ID4 promotes mammary gland development by suppressing p38MAPK activity. PMID- 22069194 TI - Evaluation of primary prostate cancer using 11C-methionine-PET/CT and 18F-FDG PET/CT. AB - OBJECTIVE: The objective of this study was to evaluate the capability of (11)C methionine (MET)-PET/CT and (18)F-2-deoxy-2-fluoro-D: -glucose (FDG)-PET/CT to diagnose primary prostate cancer using recently developed Gemini TF PET/CT (Philips Healthcare, Cleveland, OH). METHODS: Twenty men who had been referred for a diagnostic work-up for prostate cancer were enrolled in this study. MET- and FDG-PET/CT by high-resolution mode were carried out on the same day prior to prostate biopsy and each maximum standardized uptake value (SUVmax) was compared with the pathological findings. The regions of interest (about 100 mm(2) small round) were placed at standard 6 points of the peripheral zone and 4 points in the apex of the transitional zone in cases that had undergone biopsy of the internal gland. We summed two scores if a specimen had inhomogeneous Gleason scores (e.g. GS 7; 4 + 3) and doubled the score when the Gleason score was the same (e.g. GS 8; 4 * 2). We divided the tumors into three groups. If the summed Gleason score of the specimens was 5 or less, they were grouped as NG (no grade with the Gleason score). If the summed Gleason score was 6 or 7, the tumors were defined as LG (low Gleason score group), and if the summed Gleason score was 8, 9 or 10, the tumors were classified as HG (high Gleason score group). The mean SUVmax was calculated and one-way analysis of variance or Kruskal-Wallis test and the Tukey post hoc test were performed for statistical comparisons. The capabilities of MET and FDG for diagnosing prostate cancer were evaluated through analysis of the area under the curve of the receiver operating characteristic (ROC) curve. The cut-off levels of SUVmax for the highest accuracy were determined by the results of the ROC analysis, and the sensitivity, specificity and accuracy were calculated. RESULTS: The PET images, obtained with Gemini TF PET/CT, allowed visual identification of anatomical locations within the prostate gland. Among the mean SUVmax of MET, FDG early phase and FDG delayed phase, the differences between NG and HG were all statistically significant (P < 0.01). With MET the difference between NG and LG was also significant (P < 0.05). And for the elevation rate from FDG early to delayed phase, the difference between NG and HG was significant (P < 0.05). The cut-off SUVmax, sensitivity, specificity, accuracy for distinguishing between NG and LG + HG by MET, FDG early and delayed phase were 3.15/78.7/75.6/78.3, 2.81/61.7/80.0/70.7 and 3.00/62.8/78.9/70.7, respectively. And the same factors between NG + LG and HG were 3.76/70.1/89.7/82.6, 2.88/70.1/82.9/78.3 and 3.47/62.7/86.3/77.7, respectively. CONCLUSIONS: In terms of the capability to diagnose prostate cancer of high Gleason score (>=8), there was no significant difference between MET and FDG. MET appears to be useful for detecting prostate cancer of both low and high Gleason score. PMID- 22069193 TI - A conserved PTEN/FOXO pathway regulates neuronal morphology during C. elegans development. AB - The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a conserved signal transduction cascade that is fundamental for the correct development of the nervous system. The major negative regulator of PI3K signaling is the lipid phosphatase DAF-18/PTEN, which can modulate PI3K pathway activity during neurodevelopment. Here, we identify a novel role for DAF-18 in promoting neurite outgrowth during development in Caenorhabditis elegans. We find that DAF-18 modulates the PI3K signaling pathway to activate DAF-16/FOXO and promote developmental neurite outgrowth. This activity of DAF-16 in promoting outgrowth is isoform-specific, being effected by the daf-16b isoform but not the daf-16a or daf-16d/f isoform. We also demonstrate that the capacity of DAF-16/FOXO in regulating neuron morphology is conserved in mammalian neurons. These data provide a novel mechanism by which the conserved PI3K signaling pathway regulates neuronal cell morphology during development through FOXO. PMID- 22069195 TI - Advances in PET myocardial perfusion imaging: F-18 labeled tracers. AB - Coronary artery disease and its related cardiac disorders represent the most common cause of death in the USA and Western world. Despite advancements in treatment and accompanying improvements in outcome with current diagnostic and therapeutic modalities, it is the correct assignment of these diagnostic techniques and treatment options which are crucial. From a diagnostic standpoint, SPECT myocardial perfusion imaging (MPI) using traditional radiotracers like thallium-201 chloride, Tc-99m sestamibi or Tc-99m tetrofosmin is the most utilized imaging technique. However, PET MPI using N-13 ammonia, rubidium-82 chloride or O-15 water is increasing in availability and usage as a result of the growing number of medical centers with new-generation PET/CT systems taking advantage of the superior imaging properties of PET over SPECT. The routine clinical use of PET MPI is still limited, in part because of the short half-life of conventional PET MPI tracers. The disadvantages of these conventional PET tracers include expensive onsite production and inconvenient on-scanner tracer administration making them unsuitable for physical exercise stress imaging. Recently, two F-18 labeled radiotracers with longer radioactive half-lives than conventional PET imaging agents have been introduced. These are flurpiridaz F 18 (formerly known as F-18 BMS747158-02) and F-18 fluorobenzyltriphenylphosphonium. These longer half-life F-18 labeled perfusion tracers can overcome the production and protocol limitations of currently used radiotracers for PET MPI. PMID- 22069199 TI - Development of gatekeeping strategies in confirmatory clinical trials. AB - This paper discusses multiplicity issues arising in confirmatory clinical trials with hierarchically ordered multiple objectives. In order to protect the overall type I error rate, multiple objectives are analyzed using multiple testing procedures. When the objectives are ordered and grouped in multiple families (e.g. families of primary and secondary endpoints), gatekeeping procedures are employed to account for this hierarchical structure. We discuss considerations arising in the process of building gatekeeping procedures, including proper use of relevant trial-specific information and criteria for selecting gatekeeping procedures. The methods and principles discussed in this paper are illustrated using a clinical trial in patients with type II diabetes mellitus. PMID- 22069200 TI - On familywise type I error control for multiplicity in equivalence trials with three or more treatments. AB - For the all pairwise comparisons for equivalence of k (k>=2) treatments Lauzon and Caffo proposed simply to divide the type I error level alpha by k-1 to achieve a Bonferroni-based familywise error control when declaring pairs of two treatments equivalent. This rule is shown to be too liberal for k>=4. It works for k=3 yet for reasons not considered by Lauzon and Caffo. Based on the two one sided testing procedures and using the closure test principle we develop valid alternatives based on Bonferroni's inequality. The set H of intersection hypotheses reveals a rich structure, leading to the possibility to present H as a directed acyclic graph (DAG). This in turn allows using some graph theoretical theorems and eases proving properties of the resulting multiple testing problems. PMID- 22069201 TI - Robust estimation for the Cox regression model based on trimming. AB - We propose a robust Cox regression model with outliers. The model is fit by trimming the smallest contributions to the partial likelihood. To do so, we implement a Metropolis-type maximization routine, and show its convergence to a global optimum. We discuss global robustness properties of the approach, which is illustrated and compared through simulations. We finally fit the model on an original and on a benchmark data set. PMID- 22069202 TI - Nonparametric Bayesian estimation of the three-way receiver operating characteristic surface. AB - We describe a nonparametric Bayesian approach for estimating the three-way ROC surface based on mixtures of finite Polya trees (MFPT) priors. Mixtures of finite Polya trees are robust models that can handle nonstandard features in the data. We address the difficulties in modeling continuous diagnostic data with skewness, multimodality, or other nonstandard features, and how parametric approaches can lead to misleading results in such cases. Robust, data-driven inference for the ROC surface and for the volume under the ROC surface is obtained. A simulation study is performed to assess the performance of the proposed method. Methods are applied to data from a magnetic resonance spectroscopy study on human immunodeficiency virus patients. PMID- 22069203 TI - Patient safety: issues and advances. PMID- 22069205 TI - Role of effective teamwork and communication in delivering safe, high-quality care. AB - Healthcare is delivered in an extraordinary complex environment. Despite highly skilled, dedicated clinicians, there are currently unacceptably high levels of communication failures and adverse events. Effective teamwork, in conjunction with reliable processes of care, is essential for the consistent delivery of high quality care. Practical concepts and tools are provided that address the team behaviors of structured communication, effective assertion/critical language, psychological safety, situational awareness, and effective leadership. Examples of the mounting clinical evidence of improved patient outcomes and reduced harm resulting from effective teamwork training are cited. PMID- 22069204 TI - Improving quality in healthcare: start with the patient. AB - In the decade since the Institute of Medicine released To Err Is Human, patient harm from medical errors is still widespread. Healthcare has not undergone the transformative change that is needed to reduce medical errors and improve quality. This article discusses patient-centeredness as an organizing principle for transforming healthcare. We also describe important efforts that depict the shift from a provider-focused system to one that is more patient-centered. Finally, the article discusses challenges for the future and the importance of involving patients in the quest to deliver safe, quality care. PMID- 22069206 TI - Effect of e-prescribing systems on patient safety. AB - E-prescribing systems enable electronic transmissions of prescriptions to pharmacies from the provider's office. The promise of e-prescribing in regard to patient safety is reduction in the time gap between point of care and point of service, reduction in medication errors, and improved quality of care. This article will give a brief overview of e-prescribing systems, what is known about these systems and their impact on patient safety, and what challenges remain. For purposes of this article, the term "patient safety" will be used interchangeably with medication errors and adverse drug events. Although there is some evidence that e-prescribing alone and e-prescribing with medication decision support can reduce medication errors, there is also evidence that e-prescribing can be a source of medication errors. The need for more study is particularly relevant and timely, as the Centers for Medicare and Medicaid Services is strongly incentivizing providers to use e-prescribing with medication decision support. Despite concerns about efficiency and dissatisfaction, the majority of providers believe e-prescribing provides for improved patient safety. Limited evidence suggests that e-prescribing with medication decision support can improve patient safety. PMID- 22069207 TI - Reforming way medical students and physicians are taught about quality and safety. AB - The purpose of this article is to briefly review the history of how quality and safety have been addressed in the United States by those who have been teaching medical students and residents, and then discuss why and how this training must change in the future to more effectively address the problems of improving healthcare quality and safety. Although it has become clear that the curriculum in medical schools should encompass quality and safety training, medical schools have been very slow to implement the reforms that are necessary to accomplish such a goal. These changes, although desirable from a rational perspective, involve basic changes in the culture of medical schools and teaching hospitals. Moreover, the cost of implementing these changes would be very large, and, if imposed by outside agencies, would likely constitute an unfunded mandate. It should also be noted that at the present time there are very few people who are well trained to develop and teach these classes. In order to accomplish the goal of improving patient safety, it is essential that we provide much more training and knowledge regarding patient safety to medical students, including knowledge of interventions known to be effective in preventing errors; education in technical performance; information about organizational and team issues; and training in disclosing errors to patients. This training should occur early in the training of professionals, preferably while they are still in school, if such training is to change the culture of medicine. Some suggestions and plans for implementation are discussed, using some innovative programs as examples. PMID- 22069208 TI - Patient safety training simulations based on competency criteria of the Accreditation Council for Graduate Medical Education. AB - This report reviews and critically evaluates the development of 3 movements in healthcare that have had a profound impact on changes occurring at all levels of medical education: patient safety, healthcare simulation, and competency-based education (exemplified by the Accreditation Council for Graduate Medical Education). The authors performed a critical and selective review of the literature from 1999 to 2011 to identify uses of simulation to address patient safety issues aligned according to the Accreditation Council for Graduate Medical Education 6 core competencies: (1) patient care; (2) medical knowledge; (3) interpersonal and communication skills; (4) professionalism; (5) practice-based learning; and (6) systems-based practice. The research synthesis is reported to inform and provide evidence about how simulation is used to train and evaluate learners on a range of patient-safety issues for each of the core competencies: There is emerging evidence that simulation can be used in training efforts to reduce medical errors related to medical knowledge and patient care (particular invasive procedures as well as improved communication and teamwork skills). There remains limited evidence on its impact to improve patient safety related to more complex competencies of practice-based learning and systems-based practice. Simulation-based learning can lead to positive patient outcomes and reduction of medical errors particularly when used for individual skills. However, particular attention needs to be placed on the organizational context in which it is implemented if improvements in practice-based learning and systems-based practice are to be realized. PMID- 22069209 TI - Errors in transfusion medicine: have we learned our lesson? AB - The phrase "patient safety" represents freedom from accidental or preventable harm due to events occurring in the healthcare setting. Practitioners aim to reduce, if not prevent, medical errors and adverse outcomes. Yet studies performed from many perspectives show that medical error constitutes a serious worldwide problem. Transfusion medicine, with its interdisciplinary intricacies and the danger of fatal outcomes, serves as an exemplar of lessons learned. Opportunity for error in complex systems is vast, and although errors are traditionally blamed on humans, they are often set up by preexisting factors. Transfusion has inherent hazards such as clinical vulnerabilities (eg, contracting an infectious agent or experiencing a transfusion reaction), but there also exists the possibility of hazards associated with process errors. Sample collection errors, or preanalytic errors, may occur when samples are drawn from donors during blood donation, as well as when drawn from patients prior to transfusion-related testing, and account for approximately one-third of events in transfusion. Errors in the analytic phase of the transfusion chain, slips and errors in the laboratory, comprise close to one-third of patient safety-related transfusion events. As many as 40% of mistransfusions are due to errors in the postanalytic phase: often failures in the final check of the right blood and the right patient at the bedside. Bar-code labels, radiofrequency identification tags, and even palm vein-scanning technology are increasingly being utilized in patient identification. The last phase of transfusion, careful monitoring of the recipient for adverse signs or symptoms, when performed diligently can help prevent or manage a potentially fatal reaction caused by an earlier process error or an unavoidable physiologic condition. Ways in which we can and do deal with potential hazards of transfusion are discussed, including a method of hazard reduction termed inherently safer design. This approach aims to lessen risk, with elimination of a hazard or the reduction of its occurrence as primary. In blood transfusion, elimination and marked reduction of some hazards has been employed to good effect. However, there is still a heavy reliance on procedural methods in the essentially manual steps constituting the phases of the transfusion chain. Some hospitals have created a new role of transfusion safety officer to assist in the effort of monitoring, identifying, and resolving conditions that may lessen safety. PMID- 22069210 TI - Prevention of retained surgical items. AB - Reduction in retained surgical items is an important part of any operating room patient-safety effort. Any item used in an operation can result in a retained surgical item, but sponges are the most frequent and the abdomen is the most common location. Retained sponges can cause significant morbidity, and the costs associated with both prevention and treatment of retained surgical items, including legal costs, can be considerable. This review will examine counting, teamwork, radiography, and new technology as methods used to prevent retained surgical items. Even though none of these techniques individually is likely to completely prevent retained surgical items, when used together the numbers can be reduced. PMID- 22069211 TI - Mitochondrial pathology in Parkinson's disease. AB - The last 25 years have witnessed remarkable advances in our understanding of the etiology and pathogenesis of Parkinson's disease. The ability to undertake detailed biochemical analyses of the Parkinson's disease postmortem brain enabled the identification of defects of mitochondrial and free-radical metabolism. The discovery of the first gene mutation for Parkinson's disease, in alpha-synuclein, ushered in the genetic era for the disease and the subsequent finding of several gene mutations causing parkinsonism, 15 at the time of writing. Technological advances both in sequencing technology and software analysis have allowed association studies of sufficiently large size accurately to describe genes conferring an increased risk for Parkinson's disease. What has been so surprising is the convergence of these 2 separate disciplines (biochemistry and genetics) in terms of reinforcing the importance of the same pathways (ie, mitochondrial dysfunction and free-radical metabolism). Other pathways are also important in pathogenesis, including protein turnover, inflammation, and post-translational modification, particularly protein phosphorylation and ubiquitination. However, even these additional pathways overlap with each other and with those of mitochondrial dysfunction and oxidative stress. This review explores these concepts with particular relevance to mitochondrial involvement. PMID- 22069212 TI - Image analysis of small pulmonary nodules identified by computed tomography. AB - Detection of small pulmonary nodules has markedly increased as computed tomography (CT) technology has advanced and interpretation evolved from viewing small CT images on film to magnified images on large, high-resolution computer monitors. Despite these advances, determining the etiology of a lung nodule short of major surgery remains problematic. Initial nodule size is a major criterion in evaluating the risk for malignancy, and the majority of CT detected nodules are <10 mm in diameter. Also, the likelihood that the nodule is a lung cancer increases with increasing age and smoking history, and such clinical information needs to be integrated into algorithms that guide the workup of such nodules. Baseline and annual repeat screening results are also very helpful in developing and assessing the usefulness of such algorithms. Based on CT morphology, subtypes of nodules have been identified; today nodules are routinely classified as being solid, part-solid, or nonsolid. It has been shown that part-solid nodules have a higher frequency of being malignant than solid or nonsolid ones. Other nodule characteristics such as spiculation are useful, although granulomas and fibrosis also have such features, so these characteristics have not been as useful as nodule-growth assessment. Depending on the aggressiveness of the lung cancer and the size of the nodule when it is initially seen, a follow-up CT scan 1-3 months after the first CT scan can identify those nodules with growth at a malignant rate. Software has been developed by all CT scanner manufacturers for such growth assessment, but the inherent variability of such assessments needs further development. Nodule-growth assessment based on 2-dimensional approaches is limited; therefore, software has been developed for the 3-dimensional assessment of growth. Different approaches for such growth assessment have been developed, either using automated computer segmentation techniques or hybrid methods that allow the radiologist to adjust such segmentation. There are, however, inherent reasons for variability in such measurements that need to be carefully considered, and this, together with continued technologic advances and integration of the relevant clinical information, will allow for individualization of the algorithms for the workup of small pulmonary nodules. PMID- 22069213 TI - Use of in vivo real-time optical imaging for esophageal neoplasia. AB - Esophageal adenocarcinoma carries a poor prognosis, as it typically presents at a late stage. Thus, a major research priority is the development of novel diagnostic-imaging strategies that can detect neoplastic lesions earlier and more accurately than current techniques. Advances in optical imaging allow clinicians to obtain real-time histopathologic information with instant visualization of cellular architecture and the potential to identify neoplastic tissue. The various endoscopic imaging modalities for esophageal neoplasia can be grouped into 2 major categories: (1) wide-field imaging, a comparatively lower-resolution view for imaging larger surface areas, and (2) high-resolution imaging, which allows individual cells to be visualized. This review will provide an overview of the various forms of real-time optical imaging in the diagnosis and management of Barrett's esophagus and esophageal adenocarcinoma. PMID- 22069214 TI - Unravelling the mechanism of glycerol hydrogenolysis over rhodium catalyst through combined experimental-theoretical investigations. AB - We report herein a detailed and accurate study of the mechanism of rhodium catalysed conversion of glycerol into 1,2-propanediol and lactic acid. The first step of the reaction is particularly debated, as it can be either dehydration or dehydrogenation. It is expected that these elementary reactions can be influenced by pH variations and by the nature of the gas phase. These parameters were consequently investigated experimentally. On the other hand, there was a lack of knowledge about the behaviour of glycerol at the surface of the metallic catalyst. A theoretical approach on a model Rh(111) surface was thus implemented in the framework of density functional theory (DFT) to describe the above mentioned elementary reactions and to calculate the corresponding transition states. The combination of experiment and theory shows that the dehydrogenation into glyceraldehyde is the first step for the glycerol transformation on the Rh/C catalyst in basic media under He or H(2) atmosphere. PMID- 22069215 TI - Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency. AB - Fumarase deficiency is a rare autosomal recessive metabolic condition. We report on a sibship with molecularly confirmed fumarase deficiency. Prenatal findings included agenesis of the corpus callosum, ventriculomegaly, and ventriculoseptal defect. The postnatal course was significant for metabolic acidosis ultimately leading to death around 3 weeks of age. Postmortem findings were noted including swollen mitochondria with abnormal cristae on electron microscopy within the liver. Molecular testing revealed a novel whole gene deletion in conjunction with a point mutation. While the point mutation has been previously reported, the detection of a whole gene deletion has not been described to date in an individual with fumarase deficiency. PMID- 22069216 TI - Few sex differences in the use of drugs for secondary prevention after stroke: a nationwide observational study. AB - PURPOSE: This observational study describes the sex differences in the use of secondary preventive drugs after ischemic stroke in terms of prescribing and persistence. Also, sex differences in patient- and treatment-related factors associated with drug use were investigated. METHODS: In this nationwide register based study, the Swedish Stroke Register was linked to the Swedish Prescribed Drug Register for information on drugs prescribed for, and bought by, stroke patients. Background factors were included from the Swedish Stroke Register. RESULTS: Included in the database were 9331 men and 9018 women. Men were more often prescribed statins, 48.8% versus 38.1% [age-adjusted prevalence ratio (PR) = 0.86, 95%CI = 0.82-0.91], and warfarin, 38.4% versus 26.4% after stroke (age adjusted PR = 0.88, 95%CI = 0.79-0.97). There were no differences in prescribing of antihypertensive or antiplatelet drugs. No sex differences were seen regarding not continuing drug treatment after discharge (primary non-adherence). Women had slightly higher persistence to antihypertensive treatment 2 years after discharge, 76.3% versus 71.9% for men (age-adjusted PR = 1.05, 95%CI = 1.00 1.09), but there were no differences in persistence to antiplatelet, warfarin or statin treatments. Similar factors were related to statin and warfarin prescribing for both men and women. Only antihypertensive treatment before stroke was associated to persistence to antihypertensive treatment, and this increased persistence for both men and women. CONCLUSIONS: This study showed few differences between men and women after stroke. Patients' use of secondary preventive drugs needs to be improved, and from a public health perspective, poor persistence is probably a greater problem than differences between the sexes. PMID- 22069217 TI - Comparison of headspace solid-phase microextraction, headspace single-drop microextraction and hydrodistillation for chemical screening of volatiles in Myrtus communis L. AB - INTRODUCTION: Headspace solid-phase microextraction (HS-SPME) and headspace single-drop microextraction (HS-SDME) methods have never been used for the extraction and analysis of the volatile compounds of Myrtus communis. For that reason, in this work, these two techniques were compared with the traditional hydrodistillation (HD) extraction technique. OBJECTIVE: To compare SPME and SDME with HD for the extraction and analysis of Myrtus communis volatiles. METHODOLOGY: Three extraction methods, i.e. SPME, SDME and HD, coupled to gas chromatography-mass spectrometry were used and optimised for the analysis of Myrtus communis volatiles. The SPME extraction was performed on a 100 um PDMS fibre and for SDME a drop of n-octadecane containing 0.7% of menthol as internal standard was used as extracting solvent. The results were compared from different viewpoints including efficiency of extraction, different kinds of species extracted and quantity of extracted compounds with HD. RESULTS: The main analytes extracted by SPME were found to be alpha-pinene, limonene, 1,8-cineole, linalool, linalyl acetate, alpha-terpinyl acetate and geranyl acetate, whereas for SDME alpha-pinene, limonene, 1,8-cineole, linalool, linalyl acetate and beta-myrcene were extracted as major components. Hydrodistillation could extract alpha-pinene, limonene, 1,8-cineole, linalool, alpha-terpineol, linalyl acetate, alpha-terpinyl acetate, geranyl acetate and cis-isoeugenol better than other volatiles from Myrtus communis. CONCLUSION: The results demonstrated that HS-SPME and HS-SDME can be applied successfully for the extraction and separation of volatiles in aromatic plants, and these techniques are easier to perform, and more effective than HD for collection of more volatile compounds. PMID- 22069220 TI - Synthetic prodiginine obatoclax (GX15-070) and related analogues: anion binding, transmembrane transport, and cytotoxicity properties. AB - Synthetic prodiginine obatoclax shows promise as a potential anticancer drug. This compound promotes apoptosis of cancer cells, although the mechanism of action is unclear. To date, only the inhibition of BCL-2 proteins has been proposed as a mechanism of action. To gain insight into other possible modes of action, we have studied the anion-binding properties of obatoclax and related analogues in solution, in the solid state, and by means of density functional theory calculations. These compounds are well suited to interact with anions such as chloride and bicarbonate. The anion-transport properties of the compounds synthesized were assayed in model phospholipid liposomes by using a chloride selective-electrode technique and (13)C NMR spectroscopy. The results demonstrated that these compounds are efficient anion exchangers that promote chloride, bicarbonate, and nitrate transport through lipid bilayers at very low concentrations. In vitro studies on small-cell lung carcinoma cell line GLC4 showed that active ionophores are able to discharge pH gradients in living cells and the cytotoxicity of these compounds correlates well with ionophoric activity. PMID- 22069221 TI - Safety aspects of antiepileptic drugs--focus on pharmacovigilance. AB - PURPOSE: Most patients with epilepsy are dependent on a life-long pharmacological treatment with antiepileptic drugs (AEDs). AEDs include a wide range of substances that possess large pharmacological variability and are often susceptible to drug interactions and adverse drug reactions (ADRs). AEDs are increasingly used in other neurological and psychiatric disorders, and new patient groups are exposed to these drugs. The aim of the present review is to focus upon how pharmacovigilance contributes to improved safety of AEDs. METHODS: The present article is a review based on searches in Pubmed on articles from the last 15 years. Strengths and challenges regarding these aspects will be highlighted and discussed. RESULTS: The concept of pharmacovigilance includes various methods of monitoring of large patient populations with registries and databases of surveillance of ADRs and risk of suicide and sudden unexpected death, drug utilization and prescription patterns, pregnancy and birth registries and therapeutic drug monitoring (TDM) databases for studies on pharmacological variability of AEDs in large sample sizes. Challenges for existing reporting systems and databases include differences in outcome measures and thus international comparison. CONCLUSION: Continuous focus on safety aspects of AEDs and the importance of the implementation of pharmacovigilance contribute to further optimized therapy on a large scale and for the individual patient. PMID- 22069219 TI - Ex vivo spinal cord slice model of neuromyelitis optica reveals novel immunopathogenic mechanisms. AB - OBJECTIVE: Neuromyelitis optica (NMO) is a neuroinflammatory disease of spinal cord and optic nerve associated with serum autoantibodies (NMO-immunoglobulin G [IgG]) against astrocyte water channel aquaporin-4 (AQP4). Recent studies suggest that AQP4 autoantibodies are pathogenic. The objectives of this study were to establish an ex vivo spinal cord slice model in which NMO-IgG exposure produces lesions with characteristic NMO pathology, and to test the involvement of specific inflammatory cell types and soluble factors. METHODS: Vibratome-cut transverse spinal cord slices were cultured on transwell porous supports. After 7 days in culture, spinal cord slices were exposed to NMO-IgG and complement for 1 to 3 days. In some studies inflammatory cells or factors were added. Slices were examined for glial fibrillary acidic protein (GFAP), AQP4, and myelin immunoreactivity. RESULTS: Spinal cord cellular structure, including astrocytes, microglia, neurons, and myelin, was preserved in culture. NMO-IgG bound strongly to astrocytes in the spinal cord slices. Slices exposed to NMO-IgG and complement showed marked loss of GFAP, AQP4, and myelin. Lesions were not seen in the absence of complement or in spinal cord slices from AQP4 null mice. In cultures treated with submaximal NMO-IgG, the severity of NMO lesions was increased with inclusion of neutrophils, natural killer cells, or macrophages, or the soluble factors tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), IL-1beta, or interferon-gamma. Lesions were also produced in ex vivo optic nerve and hippocampal slice cultures. INTERPRETATION: These results provide evidence for AQP4, complement- and NMO-IgG-dependent NMO pathogenesis in spinal cord, and implicate the involvement of specific immune cells and cytokines. Our ex vivo model allows for direct manipulation of putative effectors of NMO disease pathogenesis in a disease-relevant tissue. PMID- 22069222 TI - Quantitative assessment of skeletal muscle degeneration in patients with myotonic dystrophy type 1 using MRI. AB - PURPOSE: To identify MRI biomarkers that could be used to follow disease progression and therapeutic efficacy in one individual muscle in patients with myotonic dystrophy type 1 (DM1). MATERIALS AND METHODS: Lower limb MRI and maximal ankle dorsiflexor strength assessment, using a hand-held dynamometer, were performed in 19 DM1 patients and 6 control subjects. The volume of residual muscle tissue of Tibialis Anterior (TA) muscle was chosen as an index for muscle atrophy, and the T2-relaxation-time of the residual muscle tissue was measured to evaluate edema-like lesions. The fat-to-water ratio was assessed using three point Dixon images to quantify fat infiltration in the entire muscle. RESULTS: The intra-observer variability of MRI indices (~5.2% for the residual muscle tissue volume and 2.5% for the fat-to-water ratio) was lower than that of the dorsiflexor torque measurement (~11.5%). A high correlation (r = 0.91) was found between maximal ankle dorsiflexor strength and residual TA muscle tissue volume in DM1 patients. Increases in the fat-to-water ratio and T2-relaxation-time were associated with a decrease in maximal ankle dorsiflexor strength. CONCLUSION: MRI appears as a noninvasive method which can be used to follow disease progression and therapeutic efficacy. PMID- 22069223 TI - Formation of giant protein vesicles by a lipid cosolvent method. AB - This paper describes a method to create giant protein vesicles (GPVs) of >=10 MUm by solvent-driven fusion of large vesicles (0.1-0.2 MUm) with reconstituted membrane proteins. We found that formation of GPVs proceeded from rotational mixing of protein-reconstituted large unilamellar vesicles (LUVs) with a lipid containing solvent phase. We made GPVs by using n-decane and squalene as solvents, and applied generalized polarization (GP) imaging to monitor the polarity around the protein transmembrane region of aquaporins labeled with the polarity-sensitive probe Badan. Specifically, we created GPVs of spinach SoPIP2;1 and E. coli AqpZ aquaporins. Our findings show that hydrophobic interactions within the bilayer of formed GPVs are influenced not only by the solvent partitioning propensity, but also by lipid composition and membrane protein isoform. PMID- 22069224 TI - Binap-gold(I) versus Binap-silver trifluoroacetate complexes as catalysts in 1,3 dipolar cycloadditions of azomethine ylides. AB - The 1,3-dipolar cycloaddition between azomethine ylides and alkenes is efficiently catalysed by [{(S(a))-Binap-Au(tfa)}(2)] (Binap=2,2' bis(diphenylphosphino)-1,1'-binaphthyl; tfa=trifluoroacetyl). Maleimides, 1,2 bis(phenylsulfonyl)ethylene, chalcone and nitrostyrene were suitable dipolarophiles even when using sterically hindered 1,3-dipole precursors. The results obtained in these transformations improve the analogous ones obtained in the same reactions catalysed by [Binap-Ag(tfa)]. In addition, computational studies have also been carried out to demonstrate both the high enantioselectivity exhibited by the chiral gold(I) complex, and the non-linear effect observed in this transformation. PMID- 22069225 TI - Long-term mental health of men who lose a wife to cancer--a population-based follow-up. AB - OBJECTIVE: This study investigated the long-term risk of psychological morbidity for men after losing a wife to cancer. A further aim of the study was to investigate if being in a new relationship at the time of follow-up affects the risk of psychological morbidity. METHOD: In a population-based cohort study, we collected data from 907 men in Sweden who lost a wife to cancer in the breast, ovary or colon 4-5 years earlier. A control group of 330 married men was also included. RESULTS: Six hundred ninety-one of the widowers (76%) and 262 of the controls (79%) answered a questionnaire. Widowers in a new relationship had a similar risk of psychological morbidity compared with a control group of married men. However, compared with widowers in a new relationship, single widowers reported increased risks of (among other symptoms) the following: depression (RR 2.2, confidence interval [CI] 1.5-3.2), anxiety (RR 1.6, CI 1.1-2.5) emotional numbness (RR 2.2, CI 1.7-2.8), and waking up at night with anxiety (RR 2.2, CI 1.4-3.7). CONCLUSIONS: Men who lost a wife to cancer in Sweden in 2000 or 2001 and are single 4-5 years later have increased risks of psychological morbidity, both compared with widowers who are in a new relationship at the time of follow up and with married men. Further scientific effort is needed for improved understanding of the most likely underlying mechanisms; that is, that enhanced emotional support of a new relationship after the loss of a wife protects against psychological morbidity, or alternatively, that the healthiest widowers enter a new relationship. PMID- 22069227 TI - Fourier analysis of STimulated echoes (FAST) for the quantitative analysis of left ventricular twist. AB - PURPOSE: To validate a novel method for the rapid and facile quantification of left ventricular (LV) twist from tagged magnetic resonance images and demonstrate the potential clinical utility in a series of 20 healthy volunteers. MATERIALS AND METHODS: Cardiac magnetic resonance imaging (MRI) short-axis images were acquired with tissue tagging in 20 healthy subjects and six canines. The tagged images were processed using a novel Fourier Analysis of the STimulated echoes (FAST) method, which uses a series of Fourier-space operations to measure LV twist with limited user interaction. A subset of eight healthy subjects and the canine data were compared to results from previously validated "gold standard" software (FindTags). Interobserver and intraobserver coefficients of variation (CV(INTER) and CV(INTRA) ), linear regression, and Bland-Altman analyses were used to assess agreement between observers and methods. RESULTS: CV(INTRA) for peak systolic twist (2.9% and 2.6%) and CV(INTER) (4.3% and 4.2%) were all small. Linear regression analysis of the FAST and FindTags twist values indicated very good agreement in healthy subjects (R = 0.91) and in canines (R = 0.95). Bland Altman comparison of the FAST and FindTags twist results indicated excellent agreement in healthy subjects (bias of -0.5 degrees , 95% confidence intervals ( 4.3 degrees , 4.3 degrees )) and canines (bias of 0.2 degrees , 95% confidence intervals (-2.7 degrees , 3.1 degrees )). Peak systolic twist in healthy subjects averaged 10.5 +/- 1.9 degrees degrees. CONCLUSION: The FAST method for quantifying LV twist produces results that are not significantly different from the current "gold standard" in a fraction of the user interaction time and has demonstrated feasibility in human subjects. PMID- 22069228 TI - 15N relaxation NMR studies of prolyl oligopeptidase, an 80 kDa enzyme, reveal a pre-existing equilibrium between different conformational states. AB - Open and closed: The characterization of protein mobility is crucial for the understanding of biological functions. We have applied NMR spectroscopy to study the conformational dynamics of the 80 kDa enzyme prolyl oligopeptidase (POP). Our results revealed that POP is highly dynamic and that inhibition of catalytic activity shifts this conformational equilibrium towards a less dynamic state. PMID- 22069229 TI - Evaluating the polar organic chemical integrative sampler for the monitoring of beta-blockers and hormones in wastewater treatment plant effluents and receiving surface waters. AB - Wastewater treatment plants (WWTP) are known to be a source of surface water contamination by organic compounds such as pharmaceuticals. The objective of the present work was to study the suitability of the polar organic chemical integrative sampler (POCIS) to monitor beta-blockers and hormones in effluents and surface waters. Four sampling campaigns were carried out in French rivers (the Saone, the Ardieres, the Bourbre, and the Seine) between November 2007 and September 2008. Passive samplers were exposed in surface waters, upstream and downstream of WWTP outflows, and in effluents. Exposures lasted for up to 24 d to study the uptake kinetics directly in situ, and repeatability was assessed by exposure of triplicates. A good agreement was found between POCIS and water samples. With the exception of atenolol, beta-blockers showed a linear uptake during at least three weeks, and their sampling rates could be determined in situ. These sampling rates were then used to calculate time-weighted average concentrations of beta-blockers in the Seine River with an overall good accuracy and repeatability. Such calculations could not be performed for hormones because of their variable occurrences and low concentrations in water and POCIS. Polar organic chemical integrative sampler therefore seems to be a suitable tool for monitoring beta-blockers in surface waters impacted by WWTP effluents. Longer exposure durations would be necessary to determine the suitability of POCIS for monitoring hormones. Finally, preliminary assays on the use of several deuterated compounds as performance reference compounds showed promising results for deuterated atenolol. PMID- 22069230 TI - Boron- and silicon-substituted [3]-1-heterodendralenes as versatile building blocks for the rapid construction of polycyclic architectures. PMID- 22069231 TI - Concise review: Cord blood banking, transplantation and induced pluripotent stem cell: success and opportunities. AB - Hematopoietic cell transplantation (HCT) has become a standard practice to treat a number of malignant and nonmalignant hematologic diseases. Bone marrow, mobilized peripheral blood, and umbilical cord blood can all serve as primary sources of cells for HCT. The number of cord blood units currently stored is large, although it represents only a fraction of potential collections. With much of the collection being sequestered in private banks for possible autologous use, there is a reason to expect that public banks may not be able to provide for the demand in coming years as use of cord blood for treatment of patients with diseases such as leukemia and lymphoma continues to increase. We suggest that a possible solution to encourage private banks to share their valuable units is to apply recent methodologies to generate induced pluripotent stem cells from cord cells and to optimize techniques to generate hematopoietic lineages from them. This strategy would allow us to take advantage of the units already collected under appropriate regulatory guidelines, to access a pristine cell that can be converted to a pluripotent cell at a much higher efficiency and in a shorter time period than other cells. The ability to potentially replenish a used cord unit with new cells, as well as extend the potential utility of cord blood for additional therapeutic applications, should allow banks to develop an appropriate business model for both private and public cord blood banks to flourish. PMID- 22069232 TI - Age and dose-limited PET-CT scan regime in lymphoma: between the devil and the deep blue sea? AB - In this study the authors speculate about hypothetical effective-dose (E) reduction through limiting post-chemotherapy PET-CT scanning to lymphoma sites previously identified on pre-treatment CT. E reductions/scan time savings are compared between post-treatment standard and theoretically limited PET-CT scans. The influence of patient age with E savings and associated clinical implication for 100 subjects are discussed. The greatest E theoretical savings of 52 and 32% for the CT contribution and combined PET-CT, respectively, were seen in patients <18 y old using limited scans in this study, with a potential mean time saving of 16 min per patient across the entire cohort. However, the limited PET-CT regime here missed a 1% rate of unexpected cancer that standard PET-CT recorded. The authors recommend performing larger scale multi-centre studies comparing PET-CT pre- and post-chemotherapy to establish full clinical efficacy of this method. PMID- 22069233 TI - 3D calculation of absorbed dose for 131I-targeted radiotherapy: a Monte Carlo study. AB - Various methods, such as those developed by the Medical Internal Radiation Dosimetry (MIRD) Committee of the Society of Nuclear Medicine or employing dose point kernels, have been applied to the radiation dosimetry of (131)I radionuclide therapy. However, studies have not shown a strong relationship between tumour absorbed dose and its overall therapeutic response, probably due in part to inaccuracies in activity and dose estimation. In the current study, the GATE Monte Carlo computer code was used to facilitate voxel-level radiation dosimetry for organ activities measured in an (131)I-treated thyroid cancer patient. This approach allows incorporation of the size, shape and composition of organs (in the current study, in the Zubal anthropomorphic phantom) and intra organ and intra-tumour inhomogeneities in the activity distributions. The total activities of the tumours and their heterogeneous distributions were measured from the SPECT images to calculate the dose maps. For investigating the effect of activity distribution on dose distribution, a hypothetical homogeneous distribution of the same total activity was considered in the tumours. It was observed that the tumour mean absorbed dose rates per unit cumulated activity were 0.65E-5 and 0.61E-5 mGY MBq(-1) s(-1) for the uniform and non-uniform distributions in the tumour, respectively, which do not differ considerably. However, the dose-volume histograms (DVH) show that the tumour non-uniform activity distribution decreases the absorbed dose to portions of the tumour volume. In such a case, it can be misleading to quote the mean or maximum absorbed dose, because overall response is likely limited by the tumour volume that receives low (i.e. non-cytocidal) doses. Three-dimensional radiation dosimetry, and calculation of tumour DVHs, may lead to the derivation of clinically reliable dose-response relationships and therefore may ultimately improve treatment planning as well as response assessment for radionuclide therapy. PMID- 22069234 TI - A study of environmental radioactivity measurements for Cankiri, Turkey. AB - This study is the first to assess the level of background radiation for the Cankiri province of Turkey. Indoor air radon concentrations were determined using Columbia Resin-39 nuclear track detectors and the average (222)Rn activity was found to be 44 Bq m(-3) (equivalent to an annual effective dose of 1.1 mSv). Measurements of gamma doses in outdoor air were performed using a portable plastic scintillation detector and the average gamma absorbed dose rate was found to be 8 MUR h(-1) (corresponding to an annual effective dose of 87.7 MUSv). Radionuclide activity concentrations in soil samples were measured through gamma ray spectrometry and the average activities were determined as 17.7, 22.3, 357 and 4.1 Bq kg(-1) for the radionuclides (238)U, (232)Th, (40)K and (137)Cs, respectively. The average annual effective dose from the natural radioactivity sources ((238)U series, (232)Th series and (40)K) was calculated to be 44.4 MUSv. Radioactivity levels of drinking water samples were carried out using a low background proportional counter and the average gross alpha and beta activities were obtained as 0.25 and 0.26 Bq l(-1), respectively (equivalent to an annual effective dose of 184 MUSv). The average radon concentrations in indoor air and the average radionuclide activities in soil were found to be lower than most Turkish cities while higher levels of outdoor gamma dose rate and water radioactivity were observed. The results of this study showed that the region's background radioactivity level differs considerably from the reported data for Turkish cities. PMID- 22069235 TI - Perfusion parameters analysis of the vertebral bone marrow in patients with Ph1- chronic myeloproliferative neoplasms (Ph(neg) MPN): a dynamic contrast-enhanced MRI (DCE-MRI) study. AB - PURPOSE: To evaluate perfusion parameters of the vertebral bone marrow in patients with Philadelphia negative chronic myeloproliferative neoplasms (Ph(neg) MPN) using dynamic contrast-enhanced MRI (DCE-MRI). MATERIALS AND METHODS: The study enrolled 24 patients with Ph(neg) MPN: 12 patients with myelofibrosis (Group A), 6 with essential thrombocythemia (ET), and 6 with polycythemia vera (PV) (Group B) who underwent DCE-MRI of the lumbosacral spine. Twelve normal individuals served as control group (Group C). Wash-in (WIN), wash-out (WOUT), maximum contrast-enhancement (CE max), time-to-peak (TTPK), time-to-maximum slope (TMSP), and the WIN/TMSP ratio (WTSP) were calculated. RESULTS: WIN, CE(max) , and WTSP parameters were higher in Group A than in Group C (P < 0.05). These parameters were significant (P < 0.0001) in discriminating patients with myelofibrosis from normal individuals with sensitivities 74.14%, 87.93%, 74.14%, and specificities 91.07%, 83.93%, 91.07%, respectively. WIN, WOUT, CE(max) , and WTSP parameters were higher in Group A than in Group B (P < 0.05). Group B exhibited no differences in perfusion parameters as compared with Group C with the exception of WOUT. CONCLUSION: Patients with myelofibrosis exhibited increased perfusion parameters in vertebral bone marrow, which could be consisted with increased vascularity, probably related to neoangiogenesis as opposed to ET or PV patients showing no increased perfusion. DCE-MRI may be of value in discriminating subgroups of Ph(neg) MPN patients and in indicating those progressing to myelofibrosis. PMID- 22069236 TI - Surface-functionalized ionic liquid crystal-supported ionic liquid phase materials: ionic liquid crystals in mesopores. AB - The influence of confinement on the ionic liquid crystal (ILC) [C(18)C(1)Im][OTf] is studied using differential scanning calorimetry (DSC), polarized optical microscopy (POM), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The ILC studied is supported on Si-based powders and glasses with pore sizes ranging from 11 to 50 nm. The temperature of the solid-to-liquid crystalline phase transition seems mostly unaffected by the confinement, whereas the temperature of the liquid-crystalline-to-liquid phase transition is depressed for smaller pore sizes. A contact layer with a thickness in the order of 2 nm is identified. The contact layer exhibits a phase transition at a temperature 30 K lower than the solid-to-liquid-crystalline phase transition observed for the neat ILC. For applications within the "supported ionic liquid phase (SILP)" concept, the experiments show that in pores of diameter 50 nm a pore filling of alpha>0.4 is sufficient to reproduce the phase transitions of the neat ILC. PMID- 22069237 TI - A critical requirement for notch signaling in maintenance of the quiescent skeletal muscle stem cell state. AB - Notch signaling plays a key role in virtually all tissues and organs in metazoans; however, limited examples are available for the regulatory role of this pathway in adult quiescent stem cells. We performed a temporal and ontological assessment of effectors of the Notch pathway that indicated highest activity in freshly isolated satellite cells and, unexpectedly, a sharp decline before the first mitosis, and subsequently in proliferating, satellite cell derived myoblasts. Using genetic tools to conditionally abrogate canonical Notch signaling during homeostasis, we demonstrate that satellite cells differentiate spontaneously and contribute to myofibers, thereby resulting in a severe depletion of the stem cell pool. Furthermore, whereas loss of Rbpj function provokes some satellite cells to proliferate before fusing, strikingly, the majority of mutant cells terminally differentiate unusually from the quiescent state, without passing through S-phase. This study establishes Notch signaling pathway as the first regulator of cellular quiescence in adult muscle stem cells. PMID- 22069238 TI - Optimization of b value in diffusion-weighted MRI for characterization of benign and malignant gynecological lesions. AB - PURPOSE: To explore the optimal b value in diffusion-weighted (DW)-MRI for differentiation of benign and malignant gynecological lesions. MATERIALS AND METHODS: Consecutive 58 patients (66 lesions) with pathologically confirmed diagnosis of gynecological disease were included in the study. Routine pelvic MRI sequences were used for defining the lesions and reviewed independently for benignity/ malignity. Single-shot echoplanar imaging (SH-EPI) DW-MRI with eight b values and nine apparent diffusion coefficient (ADC) maps were obtained. The lesions were analyzed qualitatively on DW-MRI for benignity/malignity on a five point-scale and quantitatively by measurement of apparent diffusion coefficient (ADC) values. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic accuracy of ADC values for differentiating between benign and malignant lesions. Pathology results were the reference standard. RESULTS: Differentiation between benign and malignant gynecological lesions using visual scoring was found to be successful with b values of 600, 800, or 1000 s/mm(2) . The mean ADC values of malignant lesions were significantly lower than those of benign lesions for all b value (P < 0.005). The ADCs with b = 0 and 600, 0 and 1000 s/mm(2) , 0, 600, 800 and 1000 s/mm(2) , and all b values were more effective for distinguishing malignant from benign gynecological lesions (Az = 0.851, 0.847, 0.848, 0.849, respectively). Using ADC with b = 0, 600, 800, and 1000 s/mm(2) , a threshold value of 1.20 * 10(-3) mm(2) /s permitted this distinction with a sensitivity of 83%, a specificity of 81%. CONCLUSION: DW-MRI is an important method, and the optimal b values are between 600 and 1000 s/mm(2) for differentiation between benign and malignant gynecological lesions. PMID- 22069239 TI - Assessing spin-component-scaled second-order Moller-plesset theory using anharmonic frequencies. AB - Four common parametrisations of spin-component-scaled second-order Moller-Plesset (MP2) theory are benchmarked by calculating the anharmonic vibrational frequencies of a test suite consisting of eighteen diatomic and five small molecules. Of the four methods, the scaled opposite-spin MP2 (SOS-MP2), the variable-scaling opposite-spin MP2 (VOS-MP2) and the spin-component-scaled MP2 (SCS-MP2) methods perform statistically better than standard MP2 theory, while the spin-component scaled for nucleic bases MP2 (SCSN-MP2) performs worse. Vibrations of closed-shell diatomic molecules are slightly more accurately described by the SOS-MP2 method of Head-Gordon (epsilon(MAD) =51 cm(-1) ) than the SCS-MP2 method of Grimme (epsilon(MAD) =61 cm(-1)) or the size-consistent parametrisation of VOS-MP2 (epsilon(MAD) =54 cm(-1)). For open-shell diatomic molecules, the SOS-MP2 (epsilon(MAD) =83 cm(-1)) and SCS-MP2 (epsilon(MAD) =81 cm(-1)) methods are of similar accuracy, while VOS-MP2 is slightly better (epsilon(MAD) =77 cm(-1)). Since the VOS-MP2 and SOS-MP2 methods tend to have smaller deviations from experiment, and they can be made computationally more economical than the SCS-MP2 or MP2 methods, we suggest that they should be the preferred ab initio method for computing vibrational frequencies in large molecules. PMID- 22069240 TI - Serological antibodies in inflammatory bowel disease: a systematic review. AB - The diagnosis of inflammatory bowel disease (IBD) is traditionally based on a combination of clinical, endoscopic, histological, and radiological criteria. However, further testing is needed in cases of diagnostic uncertainty and in predicting disease course. This systematic review focuses on the potential for 10 serological antibodies to fill these roles: pANCA, ASCA, anti-OmpC, anti-CBir1, anti-I2, ALCA, ACCA, AMCA, anti-L, and anti-C. We discuss their prevalence in IBD and health; their role in disease diagnosis and risk stratification; their stability over time; their presence in unaffected relatives; their association with genetic variants; and differences across ethnic groups. Serological antibodies have some role in primary diagnosis and in differentiating between Crohn's disease and ulcerative colitis. In indeterminate colitis, preoperative measurement of serological antibodies can help to predict the likelihood of complications among patients undergoing pouch surgery. The combined presence and magnitude of a large panel of antibodies appear to be of value in predicting disease progression. There is currently insufficient evidence to recommend the use of antibody testing to predict responses to treatment or surgery in patients with IBD. PMID- 22069242 TI - Photodissociation dynamics of ClCN at different wavelengths. AB - The photodissociation dynamics of small molecules in the gas and condensed phase is an important source of information for better characterizing intermolecular interactions. Herein, classical molecular dynamics simulations with provisions to follow reactive processes between different electronic states are used to probe the wavelength dependence of product state distributions after laser excitation of ClCN. It is found that the maximum of the rotational excitation distribution P(j) of the CN product shifts to lower j-values with increasing wavelength and the width of the distribution narrows. Both observations are in accord with earlier experiments and provide improvements over previous theoretical treatments of the process with the same interaction potentials. For the reaction in a water droplet, strong quenching of rotational excitation is found. PMID- 22069241 TI - Cisterna chyli in patients with portal hypertension: evaluation with MR imaging. AB - PURPOSE: To evaluate the difference in the caliber of cisterna chyli between patients with and without portal hypertension on magnetic resonance imaging (MRI) and to assess the alteration of the caliber of cisterna chyli related to contraction waves during serial T2-weighted MRI. MATERIALS AND METHODS: This study included 177 patients with and without portal hypertension who underwent two sets of T2-weighted MRI. MR images were evaluated for the visibility of cisterna chyli, the difference in the diameter of cisterna chyli between two patients groups, and the alteration in the diameter of cisterna chyli during serial T2-weighted MRI. RESULTS: The mean maximal diameter of cisterna chyli in patients with portal hypertension (4.97 +/- 1.87 mm, range; 2.5-13.1 mm) was significantly larger (P < 0.001) than that in patients without portal hypertension (3.37 +/- 1.25 mm, range; 1.5-6.8 mm). In 132 patients with visible cisterna chyli and portal hypertension, 25 (19%) patients had a positive caliber change of cisterna chyli of more than 2 mm between two sets of T2-weighted MR images. CONCLUSION: The dilatation of cisterna chyli can be demonstrated at MRI in patients with portal hypertension. Additionally, the positive caliber change of cisterna chyli related to contraction waves was observed in subsets of patients during serial T2-weighted MRI. PMID- 22069243 TI - Impact of exclusive enteral nutrition on body composition and circulating micronutrients in plasma and erythrocytes of children with active Crohn's disease. AB - BACKGROUND: Nutritional therapy is the primary treatment for active pediatric Crohn's disease (CD) in the UK/Europe, improving disease activity and anthropometry. This study assessed changes in micronutrient status during exclusive enteral nutrition (EEN). METHODS: Seventeen children (male/female: 8/9; median age: 12.7 years) with active CD were treated exclusively for 6-8 weeks on a polymeric feed (Modulen IBD; Nestle, UK). Body impedance was measured at baseline, during EEN, and posttreatment on normal diet and converted to z-scores of fat and lean mass. Blood samples for nutrient analysis were collected from 13 children at baseline, end of EEN, and posttreatment. RESULTS: Lean but not fat mass improved at the end of EEN (initiation vs. end of EEN; fat mass [z-score]: 0.5 vs. -0.3; P = 0.141; lean mass [z-score]: -2.1 vs. -0.8; P < 0.0001). At baseline several children presented with suboptimal concentrations of carotenoids, trace elements, vitamin C, B6, and folate in plasma but not in erythrocytes. EEN improved concentrations for several nutrients, but more than 90% of patients had depleted concentrations of all carotenoids. The latter improved on normal diet but other micronutrients, which improved during EEN, returned toward pretreatment concentrations. CONCLUSIONS: Lean but not fat mass improved at the end of EEN. Median concentrations for several plasma micronutrients improved on EEN but carotenoids were depleted. These findings may have implications for clinical practice and producers of enteral feeds. As plasma concentrations for many micronutrients can be affected by the acute phase response, measurements in erythrocytes may be a better marker of actual body stores. PMID- 22069244 TI - Prediction of microvascular invasion of hepatocellular carcinoma: usefulness of peritumoral hypointensity seen on gadoxetate disodium-enhanced hepatobiliary phase images. AB - PURPOSE: To determine whether peritumoral hypointensity seen on hepatobiliary phase images of preoperative gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) is useful for predicting microvascular invasion of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was approved by the Institutional Review Board. In all, 104 HCC masses in 104 patients who had undergone EOB-MRI and liver surgery within 1 month after EOB-MRI were evaluated. Two radiologists independently recorded the presence of a peritumoral hypointensity on hepatobiliary phase. Interobserver agreement was assessed and consensus records were used. Tumor size was measured. A chi-square test and independent t-test were used for univariate analysis. Multiple logistic regression was performed to determine factors for predicting microvascular invasion. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of peritumoral hypointensity were calculated. RESULTS: Sixty HCCs had microvascular invasion and 44 did not. Interobserver agreement in determining peritumoral hypointensity was excellent (kappa = 0.83). By univariate analysis, peritumoral hypointensity and tumor size were significant for predicting microvascular invasion of HCC. On multiple logistic regression analysis, only peritumoral hypointensity was significant in predicting microvascular invasion of HCC (P = 0.013). The sensitivity, specificity, PPV, and NPV of peritumoral hypointensity were 38.3%, 93.2%, 88.5%, and 52.6%, respectively. CONCLUSION: Peritumoral hypointensity on the hepatobiliary phase of EOB-MRI is not sensitive but has high specificity for predicting microvascular invasion of HCC. PMID- 22069245 TI - Colloidal crystallization of surfactant-free ZnO quantum dots. PMID- 22069246 TI - Presence of concomitant inflammatory bowel disease is associated with an increased risk of postcholecystectomy complications. AB - BACKGROUND: Surgery in patients with inflammatory bowel disease (IBD) is often associated with complications. The aim of our study was to evaluate whether concomitant IBD was associated with an increased risk of postcholecystectomy complications. METHODS: The study group consisted of 82 consecutive IBD patients who underwent cholecystectomy from January 2001 to October 2010. The control group included 296 cholecystectomy patients without IBD who were randomly selected from the cholecystectomy database. Variables were analyzed by univariate and multivariate analyses. RESULTS: There were no significant differences in age, gender, body mass index, presence of gallstones/common bile duct stones, indication for cholecystectomy, and postoperative mortality between the study and control groups. More patients in the study group had postoperative complications than in the control group (17.1% vs. 6.8%, P = 0.005). On multivariate analysis, the presence of concomitant IBD was independently associated with an increased risk for postoperative complications (odds ratio [OR] = 4.64; 95% confidence interval [CI], 1.63-13.20, P = 0.004) after adjusting for age, the presence of cirrhosis, diabetes, body mass index, the use of corticosteroids, immunomodulators, total parental nutrition, or biologics, the presence of primary sclerosing cholangitis (PSC), acute or chronic cholecystitis, cholelithiasis, or prior abdominal surgeries, and indication for surgery (elective vs. emergent). CONCLUSIONS: IBD patients undergoing cholecystectomy have a significantly increased risk of postoperative complications. Although further studies are warranted to clarify the reason for these differences, caution should be taken to determine the need and timing of cholecystectomy in IBD patients. PMID- 22069247 TI - Augmented reality and haptic interfaces for robot-assisted surgery. AB - BACKGROUND: Current teleoperated robot-assisted minimally invasive surgical systems do not take full advantage of the potential performance enhancements offered by various forms of haptic feedback to the surgeon. Direct and graphical haptic feedback systems can be integrated with vision and robot control systems in order to provide haptic feedback to improve safety and tissue mechanical property identification. METHODS: An interoperable interface for teleoperated robot-assisted minimally invasive surgery was developed to provide haptic feedback and augmented visual feedback using three-dimensional (3D) graphical overlays. The software framework consists of control and command software, robot plug-ins, image processing plug-ins and 3D surface reconstructions. RESULTS: The feasibility of the interface was demonstrated in two tasks performed with artificial tissue: palpation to detect hard lumps and surface tracing, using vision-based forbidden-region virtual fixtures to prevent the patient-side manipulator from entering unwanted regions of the workspace. CONCLUSIONS: The interoperable interface enables fast development and successful implementation of effective haptic feedback methods in teleoperation. PMID- 22069248 TI - Ultrasound and cadaveric prosections as methods for teaching cardiac anatomy: a comparative study. AB - This study compared the efficacy of two cardiac anatomy teaching modalities, ultrasound imaging and cadaveric prosections, for learning cardiac gross anatomy. One hundred and eight first-year medical students participated. Two weeks prior to the teaching intervention, students completed a pretest to assess their prior knowledge and to ensure that groups were equally randomized. Students, divided into pre-existing teaching groups, were assigned to one of two conditions; "cadaver" or "ultrasound." Those in the cadaver group received teaching on the heart using prosections, whereas the ultrasound group received teaching using live ultrasound images of the heart. Immediately after teaching, students sat a post-test. Both teaching modalities increased students' test scores by similar amounts but no significant difference was found between the two conditions, suggesting that both prosections and ultrasound are equally effective methods for teaching gross anatomy of the heart. Our data support the inclusion of either cadaveric teaching or living anatomy using ultrasound within the undergraduate anatomy curriculum, and further work is needed to compare the additive effect of the two modalities. PMID- 22069249 TI - Identification and characterization of a complex pure mosaic of small supernumerary marker chromosomes involving 11p11.12 -> q12.1 and 19p12 -> q12 regions in a child featuring multiple congenital anomalies. AB - Unstable, gene-rich pericentric regions have been associated with various structural aberrations including small supernumerary marker chromosomes (sSMCs). We hereby report on a complex pure mosaic sSMCs derived from chromosomes 11 and 19 in a child featuring multiple congenital anomalies. As indicated by microarray analysis, the sSMCs have involved materials from 11p11.12 -> q12.1 and 19p12 -> q12 in complex forms (with four cell lines harboring from 1 to 4 sSMCs) in all peripheral blood lymphocytes. The patient featured facial dysmorphism, generalized hypotonia, cryptorchidism, transverse palmar creases, cerebral hemorrhage, atrial septal defect secundum, strabismus, epilepsy, immunodeficiency, and severe cognitive and motor impairment. Literature review indicated this to be a unique sSMCs case simultaneously involving chromosomes 11 and 19, with one sSMC containing materials from the both chromosomes. We propose that the involved chromosomal regions may contain dosage-sensitive genes which are important for the development, and that the sSMCs derived from multiple origins have formed by a complex mechanism. PMID- 22069251 TI - Immunology of Diabetes Society T-Cell Workshop: HLA class I tetramer-directed epitope validation initiative T-Cell Workshop Report-HLA Class I Tetramer Validation Initiative. AB - BACKGROUND: Identification of T-cell reactivity to beta-cell antigen epitopes is an important goal for studying pathogenesis and for designing and monitoring of immunotherapeutic interventions in type 1 diabetes (T1D). METHODS: We performed a multicentre validation of known human leukocyte antigen (HLA) class I CD8+ T-cell epitopes. To this end, peripheral blood T-cell responses were measured in 35 recently (<2 years) diagnosed HLA-A*02:01+ T1D patients using blind-coded HLA-A2 tetramers (TMrs) and pentamers (PMrs), encompassing two epitopes of preproinsulin (PPI; PPIA12-20 and PPIB10-18) and two epitopes of glutamic acid decarboxylase (GAD; GAD114-122 and GAD536-545). We also compared the readout of TMrs and PMrs with a CD8+ T-cell interferon-gamma enzyme-linked immunospot assay. RESULTS: Despite the minute frequencies of autoreactive cells detected by TMrs/PMrs, most (73-77%) T1D patients had responses to one or more of the epitopes used. All four epitopes were recognized by T1D patients, with a prevalence ranging from 5 to 25%. TMrs and PMrs detected more positive responses to the beta-cell epitopes than CD8+ T-cell interferon-gamma enzyme-linked immunospot. However, concordance between positive responses to TMrs and PMrs was limited. CONCLUSIONS: Using a multicentre blind-coded setup and three different T-cell assays, we have validated PPI and GAD epitopes as commonly recognized CD8+ T-cell targets in recently diagnosed T1D patients. Both TMrs and PMrs showed higher detection sensitivity than the CD8+ T-cell interferon-gamma enzyme-linked immunospot assay. However, there are some important methodological issues that need to be addressed in using these sensitive techniques for detecting low frequency responses. PMID- 22069252 TI - Immunology of Diabetes Society T-Cell Workshop: HLA class II tetramer-directed epitope validation initiative. AB - BACKGROUND: Islet-antigen-specific CD4+ T cells are known to promote auto-immune destruction in T1D. Measuring T-cell number and function provides an important biomarker. In response to this need, we evaluated responses to proinsulin and GAD epitopes in a multicentre study. METHODS: A tetramer-based assay was used in five participating centres to measure T-cell reactivities to DR0401-restricted epitopes. Three participating centres concurrently performed ELISPOT or immunoblot assays. Each centre used blind-coded, centrally distributed peptide and tetramer reagents. RESULTS: All participating centres detected responses to auto-antigens and the positive control antigen, and in some cases cloned the corresponding T cells. However, response rates varied among centres. In total, 74% of patients were positive for at least one islet epitope. The most commonly recognized epitope was GAD270-285. Only a minority of the patients tested by tetramer and ELISPOT were concordant for both assays. CONCLUSIONS: This study successfully detected GAD and proinsulin responses using centrally distributed blind-coded reagents. Centres with little previous experience using class II tetramer reagents implemented the assay. The variability in response rates observed for different centres suggests technical difficulties and/or heterogeneity within the local patient populations tested. Dual analysis by tetramer and ELISPOT or immunoblot assays was frequently discordant, suggesting that these assays detect distinct cell populations. Future efforts should investigate shared blood samples to evaluate assay reproducibility and longitudinal samples to identify changes in T-cell phenotype that correlate with changes in disease course. PMID- 22069253 TI - Comparison of cryopreservation methods on T-cell responses to islet and control antigens from type 1 diabetic patients and controls. AB - BACKGROUND: Type 1 diabetes (T1D) is a cell-mediated autoimmune disease characterized by destruction of the pancreatic islet cells. The use of cryopreserved cells is preferable to the use of freshly isolated cells to monitor clinical trials to decrease assay and laboratory variability. METHODS: The T-Cell Workshop Committee of the Immunology of Diabetes Society compared two widely accepted T-cell freezing protocols (warm and cold) to freshly isolated peripheral blood mononuclear cells from patients with T1D and controls in terms of recovery, viability, cell subset composition, and performance in functional assays currently in use in T1D-related research. Nine laboratories participated in the study with four different functional assays included. RESULTS: The cold freezing method yielded higher recovery and viability compared with the warm freezing method. Irrespective of freezing protocol, B cells and CD8+ T cells were enriched, monocyte fraction decreased, and islet antigen-reactive responses were lower in frozen versus fresh cells. However, these results need to take in to account that the overall response to islet autoantigens was low in some assays. CONCLUSIONS: In the current study, none of the tested T-cell functional assays performed well using frozen samples. More research is required to identify a freezing method and a T-cell functional assay that will produce responses in patients with T1D comparable to responses using fresh peripheral blood mononuclear cells. PMID- 22069254 TI - Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals. AB - BACKGROUND: Recent reports have established the notion that many patients with longstanding type 1 diabetes (T1D) possess a remnant population of insulin producing beta cells. It remains questionable, however, whether these surviving cells can physiologically sense and respond to glucose stimuli. METHODS: Frozen pancreatic sections from non-diabetic donors (n=8), type 2 diabetic patients (n=4), islet autoantibody-positive non-diabetic patients (n=3), type 1 diabetic patients (n=10) and one case of gestational diabetes were obtained via the network for Pancreatic Organ Donors. All longstanding T1D samples were selected based on the detection of insulin-producing beta cells in the pancreas by immunohistochemistry. RNA was isolated from all sections followed by cDNA preparation and quantitative real-time polymerase chain reaction for insulin, glucose transporter 1 (GLUT1), GLUT2 and GLUT3. Finally, immunofluorescent staining was performed on consecutive sections for all four of these markers and a comparison was made between the expression of GLUT2 in humans versus NOD mice. RESULTS: In contrast to islets from the most widely used T1D model, the NOD mouse, human islets predominantly express GLUT1 and, to a much lesser extent, GLUT3 on their surface instead of GLUT2. Relative expression levels of these receptors do not significantly change in the context of the various (pre )diabetic conditions studied. Moreover, in both species preservation of GLUT expression was observed even under conditions of substantial leucocyte infiltration or decades of T1D duration. CONCLUSIONS: These data suggest that despite being subjected to multiple years of physiological stress, the remaining beta-cell population in longstanding T1D patients retains a capacity to sense glucose via its GLUTs. PMID- 22069255 TI - Delta-cell-specific expression of hedgehog pathway Ptch1 receptor in murine and human endocrine pancreas. AB - BACKGROUND: Hedgehog pathway plays an important role during pancreas development, when its inactivation is crucial to assure expression of pancreatic marker genes involved in the organ formation and to assure an appropriate organogenesis. Patched1 (Ptch1) is a transmembrane receptor of hedgehog pathway which has a key role in this process. In fact, heterozygous Ptch1 mutant (ptc+/-) mice are affected by an impaired glucose tolerance accompanied by reduced islet function. In the light that the cell distribution of Ptch1 receptor within the endocrine pancreas has not yet been established, we aimed at identifying the pancreatic endocrine cell subset(s) expressing such molecule. METHODS: Double immunostaining for Ptch1 and pancreatic hormones insulin, glucagon and somatostatin on pancreatic paraffin sections of C57BL/6J mice and human non-diabetic multiorgan donors was performed and analysed using confocal microscopy. In addition, diabetes was experimentally induced in mice by intraperitoneal injection of streptozotocin. Quantitative real-time polymerase chain reaction after laser capture microdissection of different islets from frozen pancreatic murine tissue sections was also performed. RESULTS: Ptch1 receptor was detected only in somatostatin-positive delta cells both in mice and in human pancreas; in mice its expression was not affected by streptozotocin treatment. A significant increase of Ptch1 mRNA expression levels in the islet periphery versus the islet core was observed by quantitative real-time polymerase chain reaction, in accord with immunohistochemical observations. CONCLUSION: Our data show a delta-cell-specific expression of Ptch1 receptor in murine and human pancreas. PMID- 22069256 TI - Imaging of pancreatic islet cells. AB - At present, the onset and progress of diabetes, and the efficacy of potential treatments, can only be assessed through indirect means, i.e. blood glucose, insulin, or C-peptide measurements. The development of non-invasive and reliable methods for (1) quantification of pancreatic beta islet cell mass in vivo, (2) determining endogenous islet function and survival, and (3) visualizing the biodistribution, survival, and function of transplanted exogenous islets are critical to further advance both basic science research and islet cell therapy in diabetes. Islet cell imaging using magnetic resonance, bioluminescence, positron emission tomography, or single photon emission computed tomography may provide us with a direct means to interrogate islet cell distribution, survival, and function. Current state-of-the-art strategies for beta-cell imaging are discussed and reviewed here in context of their clinical relevance. PMID- 22069257 TI - Imaging the pancreatic vasculature in diabetes models. AB - BACKGROUND: Vascular parameters, such as vascular volume, flow, and permeability, are important disease biomarkers for both type 1 and type 2 diabetes. Therefore, it is essential to develop approaches to monitor the changes in pancreatic microvasculature non-invasively. METHODS: Here, we describe the application of the long-circulating, paramagnetic T1 contrast agent, protected Graft Copolymer bearing covalently linked gadolinium diethylenetriaminepentaacetic acid residues and labelled with fluorescein (PGC-GdDTPA-F) for the non-invasive semi quantitative evaluation of vascular changes in diabetic models using magnetic resonance imaging. RESULTS: We observed a significantly higher accumulation of protected graft copolymer bearing covalently linked gadolinium diethylenetriaminepentaacetic acid residues and labelled with fluorescein in the pancreata of BBDR rats induced to develop diabetes, as compared to non-diabetic controls at 1 h post-injection. No differences were seen in the blood pool, kidney, or muscle, indicating that the effect is specific to the diabetic pancreas. Fluorescence microscopy revealed a marked increase in contrast agent availability in the pancreas with the development of the pathology. Similar changes were noted in the homozygous Leprdb mouse model of type 2 diabetes. This effect appeared to result both from the increase of vascular volume and permeability. CONCLUSIONS: High-molecular weight paramagnetic blood volume contrast agents are valuable for the in vivo definition of pancreatic microvasculature dynamics by magnetic resonance imaging. The increase in vascular volume and permeability, associated with diabetic inflammation, can be monitored non-invasively and semi-quantitatively by magnetic resonance imaging in diabetic BBDR rats. This imaging strategy represents a valuable research tool for better understanding of the pathologic process. PMID- 22069258 TI - Insulin as a key autoantigen in the development of type 1 diabetes. AB - Type 1 diabetes is a T-cell-mediated autoimmune disease against pancreatic beta cells. T cells target various antigens such as insulin, chromogranin A, glutamic acid decarboxylase and islet-specific glucose-6-phosphatase catalytic subunit related protein. Elimination of insulin dramatically prevents diabetes in the non obese diabetic (NOD) mouse model and response to insulin occurs prior to that to other antigens. These findings suggest that insulin is a target antigen at the early stage of the disease and is likely to be essential to cause anti-islet autoimmunity in NOD mice. In this review, we discuss whether insulin is truly essential and is only the single essential autoantigen for NOD mice and potentially for man. Although the ultimate principle is still being addressed, it is certain that T-cell response to insulin is a major check point to develop type 1 diabetes in NOD mice. Given multiple similarities between diabetes of NOD mice and man, targeting insulin and insulin-reactive T cells may provide opportunities to develop robust immunotherapies. PMID- 22069259 TI - Multiple antigens versus single major antigen in type 1 diabetes: arguing for multiple antigens. AB - Our recent review of the literature revealed that approximately 20 antigens are now known to be targeted by T cells in the NOD mouse model of the autoimmune disease type 1 diabetes. Of these, insulin has received considerable attention and has been described by some in the research community as an 'initiating' or 'single major' antigen in the disease. Insulin may indeed be worthy of these titles, at least in NOD mice and in the context of the particular major histocompatibility complex molecules expressed in this strain. However, here we present arguments in favour of viewing type 1 diabetes as a disease in which multiple antigens should be considered, rather than just one. In our view, other antigens may prove to be more worthy of these titles in humans, and the major histocompatibility complex molecules expressed may well be a determining factor. Furthermore, even if insulin is 'the initiating antigen' in type 1 diabetes, multiple pathogenic specificities are known to exist even during the prediabetic period and it is at our peril that we ignore them. The recent discovery of novel beta-cell antigens, e.g. ZnT8 and chromogranin A, has taught us that we still have much to learn about the targets of the autoimmune response in type 1 diabetes. Increased knowledge will promote a clearer picture of disease pathogenesis and will better position the field to be successful in its translational goals of immune monitoring and disease prevention and reversal. PMID- 22069260 TI - Immunization with an insulin peptide-MHC complex to prevent type 1 diabetes of NOD mice. AB - BACKGROUND: Mutating the insulin B:9-23 peptide prevents diabetes in NOD mice. Thus, the trimolecular complex of I-Ag7-insulin B:9-23 peptide-TCR may be essential for the development of spontaneous diabetes. Pathogenic T cells recognize the B:9-23 peptide presented by I-Ag7 in what is termed register 3, with the B22 basic amino acid (arginine) of the peptide bound in pocket 9 of I Ag7. Our hypothesis is that immunization with an insulin B:12-22 peptide linked to I-Ag7 in register 3 (I-Ag7-B:RE#3 complex) can induce specific antibodies to the complex, block pathogenic TCRs, and thus prevent diabetes. METHODS: We immunized young NOD mice with recombinant I-Ag7-B:RE#3 protein, in which two amino acids of the peptide were mutated to fix the peptide in register 3, and investigated the induced antibodies targeted to the peptide in register 3. RESULTS: Specific antibodies targeting I-Ag7-B:RE#3 but not I-Ag7-HEL were identified in the sera of I-Ag7-B:RE#3 immunized mice. The sera inhibited B:9-23 induced T-cell responses in vitro. I-Ag7-B:RE#3 immunization delayed progression to diabetes (versus PBS, p=0.0005), while immunization with I-Ag7-HEL control complex did not. CONCLUSIONS: Immunization with I-Ag7-B:RE#3 complex significantly delays the development of insulin autoantibodies and the onset of diabetes in NOD mice, which is associated with the induction of I-Ag7-B:RE#3 antibodies. PMID- 22069261 TI - Intracellular pathways of pancreatic beta-cell apoptosis in type 1 diabetes. AB - BACKGROUND: Apoptosis of beta cells is a feature of type 1 diabetes. It is also increasingly recognized in type 2 diabetes and islet graft rejection. METHODS: We have studied the intracellular pathways that regulate beta-cell apoptosis in type 1 and 2 diabetes. We have examined the role of Bid, a pro-apoptotic member of the Bcl-2 family, using islets from mice deficient in Bid. We also studied the Bcl-2 family molecules involved in killing by using high concentrations of reducing sugars such as glucose or ribose. RESULTS: We found that Bid-deficient islets are protected from recombinant human perforin and granzyme B, as well as from Fas mediated killing. This makes Bid a target for protection of beta cells from multiple insults relevant to type 1 diabetes. In contrast to granzyme B and death receptor signalling, we found that islets lacking Bim or Puma were protected from glucose toxicity. CONCLUSIONS: Our data indicate that different stimuli activate different initiator molecules in the Bcl-2-regulated pathway in beta cells. PMID- 22069262 TI - Role of TLR2 in the pathogenesis of autoimmune diabetes and its therapeutic implication. AB - Recently, a couple of articles suggested the possibility that apoptosis of pancreatic beta-cells induces inflammatory/immune responses to beta-cells. Such a theory is based on the assumption that apoptotic cells can, under certain circumstances, induce immune responses, inflammatory and autoimmune disorders, which is in contrast to the dogma that apoptotic cells result in immunosuppression and necrotic cells provoke inflammation/immunity. We observed that late apoptotic beta-cells with secondary necrosis elicited inflammatory responses in macrophages through the toll-like receptor 2 (TLR2)/MyD88/nuclear factor-kappaB signalling pathway. Late apoptotic cells also induced TLR2 dependent maturation of dendritic cells and then activation of autoreactive T cells. TLR2 knockout mice showed defective priming of diabetogenic T-cells by apoptotic beta-cells in the pancreatic lymph nodes. Furthermore, TLR2 deficiency conferred a significant protection against type 1 diabetes (T1D) and insulitis in T1D animal models. These findings present evidence suggesting that apoptosis of pancreatic beta-cells could be one of the initial events in T1D and provide a novel strategy for therapeutic or preventive intervention in T1D. PMID- 22069263 TI - The combination of metallothionein and superoxide dismutase protects pancreatic beta cells from oxidative damage. AB - BACKGROUND: Reactive oxygen species are considered an important cause of the death of pancreatic beta cells, thereby triggering the development of type 2 diabetes as well as failure of islet transplantation. The biological properties of metallothionein (MT) and superoxide dismutase (SOD) are likely to be related to their antioxidant and free-radical scavenging abilities, but their access across biological membranes is limited. METHODS: We investigated whether Tat-MT and Tat-SOD fusion protein could be introduced into islets by a novel protein transduction technology and protect them from oxidative damage. We used 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Annexin V/propidium iodide assays to analyse cell viability, and assessed expression of apoptosis marker proteins by Western blotting. We examined the protective effect of Tat-MT and Tat-SOD on the development of diabetes and on graft failure after syngeneic islet transplantation into Otsuka Long Evans Tokushima Fatty (OLETF) rats and Imprinting Control Region (ICR) mice, respectively. RESULTS: Tat-MT and Tat-SOD were successfully delivered into the rat islets, and reactive oxygen species, nitric oxide, glucolipotoxicity-induced cell death, cytokine injury, and DNA fragmentation due to ischaemia-reperfusion in pancreatic beta cells were significantly reduced. In addition Tat-MT and Tat-SOD treatment protected OLETF rats from developing diabetes, and enhanced the survival of antioxidant-treated islets transplanted into the renal capsules of diabetic mice. CONCLUSIONS: Transduction of Tat-MT and Tat-SOD proteins offers a new strategy for protecting against the development of diabetes by relieving oxidative stress. PMID- 22069264 TI - Administration of recombinant human thioredoxin-1 significantly delays and prevents autoimmune diabetes in nonobese diabetic mice through modulation of autoimmunity. AB - BACKGROUND: Thioredoxin as a biological antioxidant plays an important role in regulating the redox system. The administration of recombinant thioredoxin has been demonstrated to be anti-inflammatory. In this study, the effect of recombinant human thioredoxin-1 (rhTrx-1) in preventing type 1 diabetes (T1D) in nonobese diabetic (NOD) mice was evaluated. METHODS: Eight-week-old NOD mice were treated with intravenous injection of rhTrx-1 (5 ug/mouse/day) for 5 weeks (5 days a week), followed by every other day for additional 5 weeks. Diabetes onset was monitored twice a week. Pancreatic histology and beta-cell mass were examined by hematoxylin and eosin (H&E) and insulin immunohistochemistry staining, respectively. Adoptive transfer experiments were executed to assess autoimmune T cells modulated by rhTrx treatment. RESULTS: The intravenous administration of rhTrx-1 significantly delayed and prevented T1D in NOD mice. The histology data showed that rhTrx-1 treatment markedly reduced insulitic lesions and significantly preserved insulin-producing beta cells. Adoptive transfer of spleen cells from rhTrx-1-treated mice into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice significantly reduced the diabetes onset than transfer of those from phosphate-buffered saline-treated mice. Adoptive co transfer experiments demonstrated that spleen cells from rhTrx-1-treated mice significantly delayed diabetes induced by the co-transferred diabetogenic spleen cells from the new-onset diabetic mice. CONCLUSIONS: Antioxidant rhTrx-1 effectively prevents T1D which may be attributed to its activity to modulate autoimmunity. PMID- 22069265 TI - Interleukin-6 treatment induces beta-cell apoptosis via STAT-3-mediated nitric oxide production. AB - BACKGROUND: Type 2 diabetes is characterized by progressive beta-cell failure and apoptosis is probably the main form of beta-cell death in this disease. It was reported that circulating levels of interleukin-6 are elevated in type 2 diabetic patients, but whether this is involved in the pathogenesis of type 2 diabetes is still debated. In this study, we examined whether interleukin-6 can induce beta cell damage in vitro and elucidated its mechanisms. METHODS: To examine the effect of interleukin-6 on beta cells, glucose-stimulated insulin secretion (GSIS) by enzyme immunoassay (EIA) method and cell apoptosis by propidium iodide and annexin-V staining were measured in a rat beta-cell line (INS-1 or INS 832/13) after treatment with interleukin-6. The expression of apoptosis-related molecules was measured using western blotting and nitric oxide (NO) production was measured using Griess assay. AG490 and N-monomethyl-L-arginine were used to inhibit Janus kinase-mediated signal transducers and activators of transcription signalling and NO production, respectively. RESULTS: Exposure (48 h) of INS-1 cells to 20 ng/mL interleukin-6 significantly decreased GSIS as well as cell viability. We found that sub-G1/G0 population was increased as compared with untreated cells and expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, phosphorylated p38 mitogen-activated protein kinase and phosphorylated nuclear factor-kappaB was increased in interleukin-6-treated INS-1 cells. Interleukin-6 increased the amount of early apoptotic cells; this increase was blocked by AG490 or N-monomethyl-L-arginine treatment. Moreover, NO production, which is known to induce apoptosis, was increased by interleukin-6 treatment but abrogated in AG490-treated cells. CONCLUSION: Our results show that exposure to interleukin-6 for 48 h can induce beta-cell death, in part via signal transducers and activators of transcription-3-mediated NO production. PMID- 22069266 TI - Enteroviruses and type 1 diabetes. AB - BACKGROUND: Human enteroviruses, which are transmitted via a faecal-oral route, have long been associated with type 1 diabetes onset. Increased hygiene in the 20th century may now be responsible for a decreased chance of enterovirus exposure from an early age onward. Infections with enteroviruses may also be more likely to occur at a later age; the recurrent poliomyelitis epidemics in the 20th century were linked to increased hygiene, consistent with this hypothesis. The association of fewer enterovirus exposures and increased diabetes rates may seem at first non-intuitive but may be explained using a combination of human observations and data from experimental coxsackie B virus infections in nonobese diabetic mice. METHODS: Network for Pancreatic Organ Donors with Diabetes samples were examined for the presence of detectable enteroviral RNA by RT-PCR. RESULTS: Viral RNA was not detected. CONCLUSIONS: A role for enteroviruses in the aetiology of human type 1 diabetes is hard to refute but in order to definitively link enteroviruses in general, and specific viruses in particular, with the disease, pancreas biopsy tissue must become available at the time of disease diagnosis. PMID- 22069267 TI - Innate immunity in type 1 diabetes. AB - BACKGROUND: Rat models of diabetes have emerged as a powerful experimental tool for addressing the role of microbial pathogens in the mechanism of autoimmune diabetes. We have used the biobreeding diabetes resistant and LEW1.WR1 rat models to identify the role of virus-induced innate immunity in the mechanism of type 1 diabetes. METHODS: Groups of rats 21-25 days of age were left untreated, injected i.p. with 1*10(7) PFU of Kilham rat virus (KRV) only, or with 1-3 ug/g body weight-purified toll-like receptor agonists on three consecutive days and infected with 1*10(7) PFU of KRV on the following day. Spleens and pancreatic lymph nodes were recovered 5 days after infection and used for gene array analysis. To test the role of inflammation in diabetes, rats injected with KRV only or Poly(I:C) plus KRV were also administered with 2 or 0.2 ug/g body weight of dexamethasone and followed for diabetes for 40 days. RESULTS: KRV induced the expression of a vast array of proinflammatory genes in pancreatic lymph nodes on day 5 following infection. Brief dexamethasone therapy downmodulated inflammation and completely blocked diabetes. CONCLUSIONS: Our data suggest a strong association between early virus-induced proinflammatory responses and islet destruction and raise the possibility that targeting innate immune pathways in the early stages of diabetes may be a useful strategy for disease prevention. PMID- 22069268 TI - Serum CXCL1 concentrations are elevated in type 1 diabetes mellitus, possibly reflecting activity of anti-islet autoimmune activity. AB - BACKGROUND: Identification of unique inflammatory markers may facilitate prediction of type 1 diabetes mellitus (T1DM). We previously compared transcript profiles of bone marrow-derived dendritic cells from non-obese diabetic mice with those from non-obese non-diabetic mice and found that bone marrow-derived dendritic cells' expressions of inflammatory mediators, including chemokine (C-X C motif) ligand 1 (CXCL1), were three to five times higher in 4-week-old female non-obese diabetic mice than in non-obese non-diabetic mice. In humans, microarray analysis results have suggested this chemokine be a biomarker representing active anti-islet autoimmunity. We investigated whether serum CXCL1 levels, reflecting active autoimmune processes, might serve as biomarkers for T1DM. METHODS: The study groups consisted of 26 subjects with acute-onset T1DM, 20 with slowly progressive T1DM, and 20 with type 2 diabetes mellitus as disease controls. All subjects were Japanese. CXCL1 in sera were quantified by solid phase enzyme-linked immunosorbent assays. RESULTS: Serum CXCL1 levels were significantly higher in subjects with acute-onset [median 113.2 ng/mL (41.75 457.2)] or slowly progressive [median 100.8 ng/mL (32.87-225.0)] T1DM than in those with type 2 diabetes mellitus [median 71.58 ng/mL (32.45-152.6), p=0.01 and 0.03, respectively, Mann-Whitney U-test]. Decreases in fasting C-peptide levels per year correlated significantly with CXCL1 levels (n=11, r2=0.524, p=0.012) in a subpopulation of slowly progressive T1DM subjects displaying preserved beta cell function. CONCLUSIONS: To our knowledge, this is the first study to show elevated serum CXCL1 in T1DM subjects, regardless of diabetes subtype, as compared to control type 2 diabetes mellitus subjects. We propose serum CXCL1 elevation to be a good T1DM marker, possibly indicating a predisposition to autoimmune disease development. PMID- 22069269 TI - Self-reported lower respiratory tract infections and development of islet autoimmunity in children with the type 1 diabetes high-risk HLA genotype: the MIDIA study. AB - AIM: To test whether self-reported lower respiratory tract infections in early infancy predicted risk for islet autoimmunity in genetically predisposed children. METHODS: The environmental triggers for type 1 diabetes (MIDIA) study recruited newborns in Norway to identify those with the human leukocyte antigen high-risk genotype DR4-DQ8/DR3-DQ2. Of 46 939 newborns genotyped, 1003 (2.1%) carried the high-risk genotype, of whom 885 children were followed longitudinally with questionnaires and blood samples for autoantibody testing at 3, 6, 9 and 12 months of age, and then annually until 4 years of age. The endpoint (autoimmunity) was defined as positivity for at least one of three autoantibodies (to insulin, glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase like protein (IA2)) on at least two consecutive samples. The parents responded in the questionnaires, whether the child had had 'pneumonia, bronchitis or respiratory syncytial virus'. Cox proportional hazards regression models with time-dependent covariates were used to estimate hazard ratios for autoimmunity using STATA 10. RESULTS: Forty-two children developed autoimmunity, of whom 15 later developed type 1 diabetes. For 17 of the 42 cases (40%) 'pneumonia, bronchitis or respiratory syncytial virus' was reported (0.5-4 years of age) before or at the onset of autoimmunity. For 187 of the 843 non-cases (22%) 'pneumonia, bronchitis or respiratory syncytial virus' was reported in the same age group. The hazard ratio was 3.4 (p=0.001, 95% confidence interval: 1.6-7.1) for developing autoimmunity. The estimated hazard ratio was only marginally influenced by adjustment for potential confounding factors. No association was found for other infectious self-reported symptoms. CONCLUSION: Self-reported lower respiratory tract infections were associated with increased risk of islet autoimmunity in early infancy. PMID- 22069270 TI - Genetic association analyses of atopic illness and proinflammatory cytokine genes with type 1 diabetes. AB - BACKGROUND: The genetic basis of the autoimmune disease type 1 diabetes (T1D) has now been largely determined, so now we can compare these findings with emerging genetic knowledge of disorders and phenotypes that have been negatively or positively associated with T1D historically. Here, we assessed the role in T1D of variants previously reported to be associated with atopic diseases and epithelial barrier function, profilaggrin (FLG), and those that affect the expression levels of the proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, interferon (IFN)gamma and IL-18. METHODS: We genotyped single nucleotide polymorphisms (SNPs): -105/rs28665122 in SELS or SEPS1 (selenoprotein), three single nucleotide polymorphisms in IL18 (-105/rs360717, +183/rs5744292 and +1467/rs574456) and R501X/rs61816761 in FLG, the major locus associated with atopic dermatitis and predisposing to asthma, in a minimum of 6743 T1D cases and 7864 controls. RESULTS: No evidence of T1D association was found for any of the SNPs we genotyped at FLG, SELS or IL18 (p>=0.03), nor with haplotypes of IL18 (p=0.82). Review of previous T1D genome-wide association results revealed that four (human leucocyte antigen (HLA), gasdermin B/ORM1 (Saccharomyces cerevisiae)-like/gasdermin B/, GSDMB/ORMDL3/GSDMA and IL2RB) of ten loci recently reported to be associated with asthma were associated with T1D (p<=0.005). CONCLUSIONS: These results show that there are shared genetic associations for atopy-related traits and T1D, and this might help in the future to understand the mechanisms, pathways and environmental factors that underpin the rapid rise in incidence of both disorders in children. PMID- 22069271 TI - Analysis of the HLA and non-HLA susceptibility loci in Japanese type 1 diabetes. AB - BACKGROUND: We previously reported the associations of human leukocyte antigen (HLA) (DRB1 and DQB1), INS, CTLA4, IL2RA, ERBB3 and CLEC16A with Japanese type 1 diabetes (T1D). In this study, we jointly analysed these loci in addition to IFIH1 and IL7R. METHODS: A maximum of 790 T1D patients and 953 control subjects were analysed. HLA was determined by sequencing-based typing. Seven non-HLA single nucleotide polymorphisms were genotyped using TaqMan assay. RESULTS: HLA DRB1*0405, DRB1*0901 and DRB1*0802-DQB1*0302 haplotypes were positively associated with T1D, while the DRB1*15 haplotypes were negatively associated. Non HLA single nucleotide polymorphisms, INS, IL2RA, ERBB3, CLEC16A and IL7R were associated with T1D. By a prediction model using the HLA loci alone (HLA model) or the non-HLA loci alone (non-HLA model), it was revealed that the cumulative effect of the non-HLA model was much weaker than that of the HLA model (average increase in odds ratio: 1.17 versus 3.14). Furthermore, the area under the receiver operating characteristic curve of the non-HLA model was also much smaller than that of the HLA model (0.65 versus 0.81, p<10(-11)). Finally, a patient-only analysis revealed the susceptible HLA haplotypes and the risk allele of INS to be negatively associated with slower onset of the disease. In addition, the DRB1*0901 haplotype and the risk alleles of ERBB3, CLEC16A and CTLA4 were positively associated with the co-occurrence of thyroid autoimmunity. CONCLUSIONS: Although several non-HLA susceptibility genes in Japanese were confirmed trans-racially and appear to contribute to the heterogeneity of the clinical phenotypes, the cumulative effect on the ability to predict the development of T1D was weak. PMID- 22069272 TI - Role of genetics in resistance to type 1 diabetes. AB - BACKGROUND: A single nucleotide polymorphism in the mitochondrial gene encoding NADH dehydrogenase subunit 2 (mt-ND2) has been associated with reduced incidence of human type 1 diabetes (T1D). We identified the orthologue of this mitochondrial single nucleotide polymorphism in mouse and using NOD mouse models linked this genetic polymorphism to T1D resistance. The mechanism how this single nucleotide polymorphism affects the development of diabetes is studied using mouse models and beta cell lines. METHODS: The impact of this single nucleotide polymorphism on mitochondrial function and resistance to reactive oxygen species was assessed. For these studies we measured oxygen consumption by isolated mitochondria under different doses of nitric oxide. In addition, alloxan sensitivity of beta cell lines was tested using the MTT method to measure cell survival. RESULTS: mt-Nd2a is associated with protection against mouse T1D and alloxan-induced diabetes. Mice with mt-Nd2a exhibited resistance to transfer of diabetes by single clone of diabetogenic CD4+ or CD8+ T cells. Beta cell line with mt-Nd2a resist in vitro attack of diabetogenic CD8+ cytotoxic T cells, as well as free radicals generated by alloxan; isolated mitochondria with mt-Nd2a showed lower reactive oxygen species production and were more resistant to nitric oxide. CONCLUSION: mt-Nd2a protects against T1D in mouse models. The protection is at beta cell level and is associated with resistance against reactive oxygen species-mediated damage and death. PMID- 22069273 TI - Characterization of the regulatory roles of the SUMO. AB - BACKGROUND: Type 1 diabetes is a multi-factorial autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas; both genetic and environmental factors are thought to contribute to its development. Recently, a novel gene encoding small ubiquitin-like modifier protein 4 (SUMO4) was cloned and a single nucleotide substitution (M55V) was found to be strongly associated with type 1 diabetes. SUMO4 was shown to interact with IkappaBalpha and inhibit NFkappaB transcriptional activity. The M55V substitution of SUMO4 may affect its ability to modify IkappaBalpha by sumoylation, and so lead to activation of NFkappaB and transcription of genes implicated in the development of type 1 diabetes. However, the effects of sumoylation on immune cells are poorly understood. METHODS: Human SUMO1, 2, 3, 4 and mouse SUMO2 (mSUMO2) were cloned and overexpressed in dendritic, T and B cells using retroviral transduction. We then investigated whether SUMO overexpression affected their functions in vitro. To study the function of mSUMO2 in vivo, we made transgenic mice overexpressing mSUMO2 in T cells and pancreatic beta cells and compared them with transgenic mice expressing a super-repressor of NFkappaB (a dominant negative form of NFkappaB, IkappaBalphaDeltaN) in T cells. Diabetes was induced in the two groups of mice by i.p. injection of streptozotocin. RESULTS: Human SUMO1, 2, 3, 4 and mSUMO2 were all found to negatively regulate the transcriptional activity of T, B and dendritic cells. Although mSUMO2 overexpression in dendritic cells did not alter the expression of major histocompatibility complex class II proteins or B7, IL-1, IL-6 and IL-7, IL-12 expression decreased, switching Th1-directed immune responses into Th2 responses. Unlike T cells from the IkappaBalphaDeltaN mice, mSUMO2 overexpression in T cells suppressed the production of both Th1 and Th2 cytokines. Whereas the mice overexpressing IkappaBalphaDeltaN were completely protected against diabetes, those expressing mSUMO2 had the same susceptibility to diabetes as wild type. CONCLUSION: These results indicate that at least in T cells, whereas NFkappaB has pro-apoptotic activity, mSUMO2 plays a more complex role in the development of autoimmune diabetes. The relative influence of NFkappaB and sumoylation on the development of autoimmune diabetes in vivo may vary depending on the developmental stage and cell type. PMID- 22069274 TI - Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity. AB - BACKGROUND: The current paradigm that microRNAs represent a new layer of gene regulation has generated much interest in this field. MicroRNAs have emerged as important regulatory factors involved in the developmental processes and in the regulation of insulin secretion and signalling. Furthermore, recent studies revealed an altered microRNA profiling in lymphocytes of patients with autoimmune diseases like multiple sclerosis, in which a hyperexpression of miR-326 was reported. Here, we analysed the expression levels of miR-326 in peripheral blood lymphocytes from type 1 diabetic (T1D) patients in relationship with ongoing islet autoimmunity. METHODS: Peripheral blood lymphocytes were obtained from 19 T1D patients; 4/19 patients were positive for both glutamic acid decarboxylase (GAD) and islet cell antigen 512 autoantibodies; 10/19 were single GAD or IA-2 Ab positive and 5/19 were GAD antibodies and IA-2 antibodies (IA-2A) negative. Quantitative analysis of miR-326 was performed using specific stem-loop primers followed by real-time polymerase chain reaction. All values were normalized to endogenous control U6. RESULTS: miR-326 resulted increased in Ab-positive versus Ab-negative T1D subjects. Its expression levels were 2.05+/-0.38-fold increased in peripheral blood lymphocytes from patients expressing both GADA and IA-2A and 2.93+/-0.46-fold increased in single Ab-positive versus Ab-negative individuals (p<0.05). CONCLUSION: In conclusion, we have shown that miR-326 is expressed at higher levels in T1D subjects with ongoing islet autoimmunity, similar to what has been observed in multiple sclerosis, in which levels of this microRNA were highly correlated with disease severity. Interestingly, an online search of miR 326 predicted targets revealed vitamin D receptor and Erythroblastosis virus E26 oncogene homologue 1, two molecules highly involved in immune regulation. PMID- 22069275 TI - Evidence for the role of STAT4 as a general autoimmunity locus in the Korean population. AB - BACKGROUND: Recently, the association of a common STAT4 haplotype with type 1 diabetes (T1D) as well as rheumatoid arthritis has been documented in Caucasians and Koreans. STAT4 is involved in the signalling of interleukin-12 and gammaIFN, as well as interleukin-23. To discover genes affecting the susceptibility of common autoimmune diseases, we studied the association of polymorphisms in STAT4 with autoimmune thyroid disease (AITD) as well as T1D in the Korean population. SUBJECTS AND METHODS: Four single-nucleotide polymorphisms on the chromosome 2q (rs11889341, rs7574865, rs8179673, and rs10181656), which were found to associate with rheumatoid arthritis were examined for association in a Korean sample of 428 AITD, 418 T1D patients, and 1060 controls. RESULTS: The minor alleles of all four single-nucleotide polymorphisms and the reconstructed STAT4 haplotypes conferred significant degree of risk for AITD (p=10(-2) to 10(-4)). Although we found a weak association of rs11889341 with T1D (p<0.05), the same haplotypes were not associated with T1D susceptibility. When we stratified T1D patients according to the age of onset, the minor alleles of all four single-nucleotide polymorphisms and the same haplotypes showed significant association with the susceptibility of T1D in the early-onset subgroup (p<0.01), not in the late-onset subgroup. CONCLUSION: STAT4 alleles and the same haplotypes might influence cytokine signalling, and therefore the development of AITD as well as T1D. These results reinforce the influence of STAT4 gene as a general autoimmune gene. PMID- 22069276 TI - Killer cell immunoglobulin-like receptor along with HLA-C ligand genes are associated with type 1 diabetes in Chinese Han population. AB - OBJECTIVE: Killer cell immunoglobulin-like receptor (KIR) genes and their putative ligands human leukocyte antigen (HLA)-C genes have been associated with type 1 diabetes (T1D). We hypothesize that KIR genes and their ligands HLA-C genes are important in T1D aetiology. RESEARCH DESIGN AND METHODS: KIR and HLA-C ligand genotyping was performed in 259 T1D patients and 262 healthy children. RESULTS: No significant difference was observed in the distribution of KIR genes between T1D patients and healthy controls. However, frequency of HLA-C1 gene and HLA-C2 gene (marginal association) was higher in patient group. The combinations 2DL2-/HLA-C1+; 2DL3+/HLA-C1+; 2DS2-/HLAC1+ were positively associated with T1D. The combinations 2DL1+/HLA-C2-; 2DL2-/HLA-C1-; 2DL3+/HLA-C1-; 2DS2-/HLAC1- were found to be negatively associated with T1D. Among the genes we tested, a combination of HLA-C1 and -C2 conferred the strongest association with T1D and the strength of this association was higher than that of HLA-C1 alone. The frequencies of KIR 2DL1, 2DL2 and 2DL3 and HLA-C1 were higher in T1D patients positive for GAD65 autoantibody; frequency of KIR 2DS4 is higher in T1D patients positive for IA-2 autoantibody. The association between KIR/HLA-C gene and autoantibody status was not statistically significant after applying Bonferroni correction. CONCLUSION: In our study of a Han population (East China), we found no direct association of KIR genes with T1D. However, a combination of HLA-C1 and -C2 showed a positive association with T1D. Different combinations of HLA-C and KIR showed positive and negative association with T1D. PMID- 22069277 TI - Susceptibility influence of a PTPN22 haplotype with thyroid autoimmunity in Koreans. AB - BACKGROUND: Considerable amount of evidences in the Caucasians have suggested the association of a missense single-nucleotide polymorphism (SNP) in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene (rs2476601) with several autoimmune diseases including autoimmune thyroid diseases (AITD) and type 1 diabetes (T1D). As the SNP was reported to be non-polymorphic in Asians, we attempt to explore an association of PTPN22 without restricting to the rs2476601 with AITD or T1D in Korean population. METHODS: We studied 389 T1D, 212 AITD (84 Graves' disease and 128 Hashimoto's thyroiditis) patients and 225 controls. In addition to the rs2476601, we selected five testing SNPs spanning 58 kb over the PTPN22 gene using the previous resequencing data and International HapMap Project. RESULTS: We found that neither alleles, genotypes among all five SNPs, nor reconstructed haplotypes of five SNPs were associated with T1D. Interestingly, a minor allele of a SNP (rs12730735) and a haplotype (GGCTT) showed significant association with the susceptibility of AITD, especially with that of Hashimoto's thyroiditis (p<0.01). CONCLUSIONS: These results indicate that the PTPN22 gene polymorphism independent of the SNP rs2476601 might be a supplementary risk factor to AITD, but not in T1D in Koreans, contradicting a major contributory influence of the PTPN22 gene in explaining common mechanism underlying multiple autoimmune diseases. PMID- 22069278 TI - Mapping of conformational autoantibody epitopes in ZNT8. AB - BACKGROUND: Identification of the major humoral epitopes in zinc transporter 8 (ZnT8) will expand the range of biomarkers for human type 1 diabetes and may provide clues to the mechanisms governing disease progression. Our initial studies suggested that most ZnT8-reactive sera recognize conformational epitopes in the final 100aa region of the molecule. Subsequently we identified residue 325 as a major determinant in two epitopes linked to a genetic polymorphism with high minor allele frequency (rs13266634). The goal of the current study was to extend this analysis to identify non-polymorphic epitopes in ZnT8. METHODS: Although the carboxy-terminal domains of human and mouse ZnT8 are ~80% identical, the mouse probe is not precipitated by the majority of human type 1 diabetes sera. Thus to identify key residues we systematically 'humanized' the mouse probe at each position that differs and evaluated the probes in radio-immunoassays. RESULTS: As previously reported, only the alteration of Q>R325 by itself showed any restoration of binding to human sera. However, when clusters of structurally adjacent variant residues were also changed an additional region of antigenicity was revealed that depended on residues R332, E333, K336, and K340. Using a panel of 112 sera from recent onset subjects tested with the hC325Q and m R325R332E333K336K340 probes, 39.3% of the subjects were ZnT8(Q)A+ , of which 38.6% (17/44) also recognized the mouse probe. CONCLUSIONS: We conclude that the mR-REKK probe identifies a third major epitope in ZnT8 that may add to the diagnostic utility of measuring autoantibodies to this molecule. PMID- 22069279 TI - Development of a novel autoantibody assay for autoimmune gastritis in type 1 diabetic individuals. AB - BACKGROUND: Autoimmune atrophic body gastritis (ABG) and pernicious anaemia are prototypical, organ-specific autoimmune diseases whose prevalence in the general population is 2.0 vs 2 and 0.15-1%, respectively. The incidence of disease increases with age and is frequently associated with other autoimmune disorders such as type 1 diabetes mellitus (T1DM). Early diagnosis of ABG/pernicious anaemia is essential for the prevention and/or treatment before manifestations of chronic disease become irreversible. Parietal cell autoantibody detection via enzyme-linked immunosorbent assay is currently the most widely used biomarker of disease with diagnosis confirmed by subsequent immunohistochemistry via biopsy. METHODS: To improve the assay we designed a specific, molecularly defined radioimmunoprecipitation assay for early detection of ABG, targeting its major antigen, the gastric H+/K+ ATPase 4A subunit ATP4A. RESULTS: The major antigenic domain in ATP4A was tested against a panel of sera from new onset patients with T1DM which tested positive for the gold standard T1DM autoantibodies (IAA, IA2A, GAD65A, and ZnT8A). Significant immunoreactivity to ATP4A was measured (25%) while 6% of first-degree relatives of subjects with T1DM who were sero-negative for T1DM autoantigens were positive for ATP4A autoantibodies. ATP4A antibody prevalence increased with age of onset of T1DM, which is atypical of other T1DM autoantibodies. Immunoreactivity to ATP4A, unlike that of T1DM antigens, demonstrates a significant gender bias in newly diagnosed individuals with T1DM. CONCLUSION: Although the utility of the assay as a biomarker for T1DM is likely limited, it may serve as an improved indicator of ABG. PMID- 22069280 TI - LIPS islet autoantibody assays in high-throughput format for DASP 2010. AB - BACKGROUND: For cost-effective population-based diabetes prediction and confirmation, islet autoantibody assays must be made more economical. METHODS: We evaluated glutamic acid decarboxylase (GAD)-Ruc (renilla luciferase) and IA2ic (also known as ICA512ic)-Ruc (renilla luciferase) fusion protein constructs in high-throughput islet antibody assay formats. RESULTS: Antigen production via transfection onto COS cells in 100 mm culture dishes yielded sufficient antigen to assay 375 and 535 serum samples for GAD and IA2ic per dish, respectively. Antigen was usably stable after -80 degrees C storage for 40-80 days after which luciferase activity decreased. The mean signal-to-noise ratios for luciferase based immunoprecitation system (LIPS) GAD and LIPS IA2ic were 88+/-24 and 219+/ 89, respectively, comparing favourably to radio-binding assays (RBA) in the same format. However, the coefficient of variation among triplicate wells was higher for IA2ic than for GAD in LIPS, similar to findings in RBA format. Correlation coefficients between autoantibody indices determined from the RBA and LIPS methods were only R2=0.79 and R2=0.75 for GAD and IA2ic, respectively, raising the possibility that different epitopes were favoured in the two different assay formats. Nevertheless, overall concordance for the two assay types was high, at 228/240=95.0% for GAD and 494/521=94.8% for IA2ic. Using optimal cutoffs, Diabetes Autoantibody Standardization Program (DASP) 2010 sensitivity/specificity was 80/99% for GAD RBA, 80/99% for GAD LIPS, 70/98% for IA2 RBA, and 72/99% for IA2 LIPS. CONCLUSION: The LIPS assays for islet autoantibodies to GAD and IA2ic performed as well as RBA in DASP 2010. With further refinements in expression and storage, these assays may be more economical than current methods to measure islet autoantibodies in type 1 diabetes. PMID- 22069281 TI - Zinc transporter 8 autoantibodies in fulminant, acute-onset, and slow-onset patients with type 1 diabetes. AB - BACKGROUND: The aim of this study was to determine the prevalence and role of autoantibodies to zinc transporter 8 (ZnT8A) in three forms (fulminant, acute onset, and slow-onset) of Japanese patients with type 1 diabetes. METHODS: One hundred and ninety-six new-onset patients with type 1 diabetes were studied: 85 were fulminant, 81 acute-onset, and 30 slow-onset type 1 diabetes. ZnT8A were determined by radioimmunoassay using a hybrid ZnT8 carboxy-terminal construct (aa268-369) carrying 325Trp and 325Arg. Furthermore, ZnT8A epitopes were analysed using ZnT8 constructs incorporating the known aa325 variants (Trp, Arg, and Gln). RESULTS: ZnT8A were detected in 58% patients with acute-onset and 20% with slow onset type 1 diabetes (p<0.0005). In contrast, none of sera from fulminant type 1 diabetes were reactive to ZnT8 construct. Conversion of Arg or Trp to Gln at aa325 abolished reactivity in 59% of patients with an age of onset>10 years, which was significantly higher than that in patients<=10 years of age (33%, p<0.05). CONCLUSIONS: These results suggest that ZnT8A are an additional useful marker for acute-onset type 1 diabetes, but not a diagnostic marker for fulminant type 1 diabetes, and ZnT8A epitope recognition is different according to the onset age. PMID- 22069282 TI - Discordant association of islet autoantibodies with high-risk HLA genes in Chinese type 1 diabetes. AB - BACKGROUND: To reveal the aetiology of diabetes, the relationships between the islet autoantibodies, human leukocyte antigen (HLA)-A and DRB1 genotypes in the Chinese patients with type l diabetes (T1D) were investigated in our study. METHODS: In the cross-sectional and case-control study, peripheral blood samples were collected from 600 T1D patients and 102 healthy controls. The genetic polymorphisms of HLA-A and DRB1 are examined with polymerase chain reaction sequence oligonucleotide probe method. The zinc transporter 8 antibody (ZnT8A), glutamic acid decarboxylase antibody (GADA) and protein-tyrosine-phosphatase-2 autoantibody (IA2A) were detected by radioligand assay. RESULTS: The A*2402, DRB1*0301, DRB1*0405 and DRB1*0901 alleles, and A*1101-DRB1*0901, A*2402 DRB1*0405 and A*2402-DRB1*0901 haplotypes were associated with T1D (all p<0.05). The positive rates of ZnT8A in patients carried DRB1*0901, IA2A in patients carried DRB1*0405 and A*1101-DRB1*0901 and GADA in patients carried DRB1*0901 and A*2402-DRB1*0901 were significantly higher than those not carried (p<0.05). HLA DRB1*0901 was the independent risk factor of positive antibody in T1D patients. In addition, higher body mass index is also related with the loss of islet function besides high-risk HLA gene and islet autoantibody (p<0.05). CONCLUSIONS: The discordant association of autoantibodies with high-risk HLA gene may indicate the different immunology mechanisms of those autoantibodies. And metabolic burden resulting from overweight may accelerate apoptosis of beta cells. PMID- 22069283 TI - An improved method for growing and analysing human antigen-specific CD4+ T-cell clones. AB - BACKGROUND: T-cell clones are valuable tools for investigating T-cell specificity in type 1 diabetes. Efficient methods for isolating T-cell clones have been developed, but growing enough cells to undertake a detailed analysis remains a challenge. METHODS: We optimized the conditions for isolating and growing antigen specific human CD4+ effector T-cell clones. T-cell clones were isolated by FACS sorting antigen-responsive cells identified by carboxylfluorescein diacetate succinimidyl ester (CFSE) dilution. The cloning efficiency was compared between T cells cloned in the presence of 21 different combinations of cytokines. Following cloning, the growth of cloned T cells in the presence of seven different combinations of cytokines was compared. Finally, we sought a quicker and more sensitive assay to measure cloned T cells' responses to antigen. RESULTS: IL-2+IL 4 were optimal for cloning antigen-specific CD4+ T cells. Following cloning, the most antigen-specific CD4+ T-cell clones grew in the presence of IL-15+IL-21. Antigen recognition by T cells cloned and grown under these conditions was readily detected by the increase in the expression of CD25. Induction of CD25 was a more sensitive measure of antigen recognition than 3H-thymidine incorporation assays. These findings were confirmed with two proinsulin-specific CD4+ T-cell clones isolated from an individual with type 1 diabetes. CONCLUSION: The optimal cytokines for isolating, and growing, proinsulin-specific human, CD4+ T-cell clones are IL-2+IL-4 and IL-15+IL-21, respectively. Antigen recognition, by clones isolated and grown under these conditions is best detected by the induction of CD25. PMID- 22069284 TI - 'Sensing' the link between type 1 and type 2 diabetes. AB - Obesity-associated insulin resistance is a core element of metabolic syndrome and type 2 diabetes (T2D). Notably, insulin resistance is also a feature of type 1 diabetes (T1D), where findings in the non-obese diabetic mouse model have implicated transient receptor potential vanilloid-1 (TRPV1+) sensory neurons in local islet inflammation and glucose metabolism. Here, we briefly review the role of TRPV1 in non-obese diabetic (NOD) T1D pathogenesis, highlighting commonalities that suggest TRPV1 may contribute to obesity and T2D as well. With the recently discovered importance of adipose infiltrating lymphocytes in the metabolic disturbances of obesity and T2D, sensory innervation of fat may thus play an analogous role to sensory neurons in the islet--modulating neuroendocrine homeostasis and inflammation. In such a scenario, TRPV1+ sensory nerves would provide the pathoaetiological link connecting the shared metabolic and immunologic features of type 1 diabetes and T2D. PMID- 22069286 TI - Preservation of recall immunity in anti-CD3-treated recent onset type 1 diabetes patients. AB - BACKGROUND: The safety of any immune modulating agent in type 1 diabetes mellitus (T1DM) involves its selectivity on autoimmunity and its preservation of recall and tumour immunity. METHODS: We performed lymphocyte proliferation tests on seven recent onset diabetic patients treated with anti-CD3 (Otelixizumab; ChAglyCD3) and five recent onset diabetic patients treated with placebo, on average 2 years after therapy. RESULTS: Proliferative responses towards common viral, bacterial and yeast antigens upon in vitro stimulation with a range of recall antigens in anti-CD3-treated T1DM patients were highly similar to those in placebo-treated T1DM patients. Similarly, T-cell responses towards autoantigens were equally low between the two groups, several years after diagnosis of T1DM. The proliferative response upon stimulation with the human suppressor protein p53 was invariably high in both anti-CD3- and placebo-treated patients, implying preserved anti-tumour immunity in anti-CD3 treatment. CONCLUSIONS: As long-term focus on side effects is key, we demonstrate in this sub-cohort of recent onset T1DM patients treated with Otelixizumab that recall immunity is preserved in spite of high-dose anti-CD3 treatment, adding to the safety of anti-CD3 treatment as an immune-modulatory agent in the treatment of T1DM. PMID- 22069287 TI - Encapsulated pancreatic progenitors derived from human embryonic stem cells as a therapy for insulin-dependent diabetes. AB - BACKGROUND: Cellular-based therapies for insulin-dependent diabetes are potential means of achieving and maintaining normal blood glucose levels (BGL) without the need for insulin administration. Islets isolated from donor pancreases have been the most common tissue used to date, but supply is a limiting factor. The use of human embryonic stem cells (hESC) as a therapy became a possibility with the report that these cells could be differentiated to pancreatic progenitors (PP) over 12 days in vitro. Conversion of PP to glucose-responsive insulin-secreting cells can be achieved by transplanting the progenitors in vivo where cell maturation occurs. To date this step has not been shown under in vitro conditions. METHODS: Prior to transplanting, cells are encapsulated in alginate to prevent the immune cells of recipient attacking the graft. The alginate capsules have pores with a molecular weight cut-off of 250 kDa. These are too small to allow entry of immune cells, but large enough for passage of nutrients and insulin. RESULTS: Encapsulated insulin-producing cells survive and function when transplanted, and have been shown to normalize BGL when allografted into diabetic mice. As few as 750 encapsulated human islets are sufficient to normalize BGL of diabetic non-obese diabetic severe combined immunodeficient (NOD/SCID) recipient mice for at least 2 months. The safety of transplanting encapsulated human islets as demonstrated by the lack of major adverse events and infection was recently shown in a first-in-human clinical trial. Finally, fetal porcine islet-like cell clusters, which are akin to PP derived from ESC, mature and normalize BGL of diabetic recipient mice with the same efficiency as non encapsulated clusters placed under the kidney capsule. CONCLUSION: Transplanting encapsulated PP, derived from hESCs, into diabetic recipients is the strategy that is now being explored in the Australia Diabetes Therapy Project. PMID- 22069285 TI - Mast cell stabilization: novel medication for obesity and diabetes. AB - Mast cells are essential in allergic responses and beyond. White adipose tissue from obese humans contains large numbers of mast cells. Serum mast cell tryptase levels are also significantly higher in obese subjects than in lean subjects, suggesting a role of these inflammatory cells in obesity and diabetes. Two types of mast cell-deficient mice, along with corresponding wild-type control mice, were fed a Western diet to induce obesity and diabetes. We also used two anti allergy drugs, cromolyn and ketotifen (Zaditor), to treat wild-type mice during intake of a Western diet or after the onset of obesity and diabetes, to examine the possible prevention or reversal of these conditions. Mast cell deficiency or pharmacological stabilization reduced body weight gain and improved glucose and insulin sensitivities. These common, side effect-free drugs also reduced pre established obesity and diabetes without noticeable toxicity. Mechanistic studies suggest that mast cells participate in these metabolic disorders by affecting energy expenditure, protease expression, angiogenesis, apoptosis, and preadipocyte differentiation. These observations open a new era of basic research regarding mast cells, and offer hope to patients suffering from these metabolic disorders. PMID- 22069288 TI - 1,25-Dihydroxyvitamin D3 alters murine dendritic cell behaviour in vitro and in vivo. AB - BACKGROUND: Differentiation and maturation of dendritic cells yield a cell type with the ability to prime immune responses towards defence and destruction. 1,25(OH)2D3, the active form of vitamin D3, fosters the development of tolerogenic dendritic cells. This study aimed to evaluate the effects of 1,25(OH)2D3 on murine dendritic cell behaviour in vitro and in vivo. METHODS: Dendritic cells were differentiated from bone marrow cells of female C57Bl/6 mice in the presence or absence of 10(-8) M 1,25(OH)2D3 for 8 days (IL4 and GM-CSF). Maturation was induced for 48 h (IFNgamma, LPS and BALB/C islet homogenate antigen). RESULTS: Bone marrow-derived dendritic cells displayed a different surface marker profile in the presence of 1,25(OH)2D3 with decreased MHC II, CD86 and CD80 and increased CCR5, DEC205, F4/80 and CD40, as well as lower IL6 and IL12 expression upon LPS/IFNgamma stimulation. T-cell proliferation was significantly reduced when exposed to islet antigen-loaded 1,25D3-DCs as compared to control dendritic cells and IL4, IL10, TNFalpha and TGFbeta levels were increased. In vivo, transfer of islet antigen-loaded control dendritic cells resulted in priming of the immune system and hyperacute islet allograft rejection (4/4), whereas this was prevented in 5/7 mice treated with islet antigen-loaded 1,25D3-DCs. CONCLUSION: We conclude that in vitro 1,25(OH)2D3 exposure alters dendritic cell behaviour, converting them into a cell type that drives T cells away from destruction towards a regulatory phenotype. PMID- 22069289 TI - The effect of vitamin D supplementation on peripheral regulatory T cells and beta cell function in healthy humans: a randomized controlled trial. AB - BACKGROUND: Increasing evidence supports the role of vitamin D (vitD) in modifying the risk to develop type 1 diabetes (T1D) and other autoimmune diseases. VitD3 might stimulate regulatory T cells (Tregs), a central player in the maintenance of self-tolerance. In addition, direct effects of vitD on beta cell function are postulated. The aim of our study was to evaluate the effect of a high dose vitD supplementation on Tregs frequency (%Tregs) and beta-cell function assessed by a mixed meal tolerance test (MMTT) in healthy humans. METHODS: A double-blind, placebo controlled trial was performed in 59 healthy adult subjects (49% females). Subjects received oral vitD3 (140,000 IU monthly) or placebo for 3 months. %Tregs within 20,000 CD4+ T cells of peripheral blood was determined by multi-parametric FACS-analysis. A liquid MMTT was carried out before and after treatment. RESULTS: %Tregs increased significantly in the vitD group, but remained unchanged in the placebo group. Fasting C-peptide concentrations did not change significantly in either group. Similarly, the mean AUC for C-peptide after 3 months and the change in mean values from baseline to the end of the treatment were comparable in both groups. CONCLUSIONS: A short time high dose vitD3 supplementation significantly increased the frequency of Tregs, but did not further improve beta-cell function in apparently healthy subjects. The immunomodulatory potential of vitD might be an important mechanistic link for the association of vitD and T1D. PMID- 22069290 TI - Immune regulation by CTLA-4--relevance to autoimmune diabetes in a transgenic mouse model. AB - BACKGROUND: The importance of cytotoxic T lymphocyte antigen-4 (CTLA-4) in immune regulation is unquestioned, yet a precise understanding of which cells express it, and how it mediates immune inhibitory function, is lacking. Regulatory T cells are known to constitutively express CTLA-4 intracellularly, whereas conventional T cells require activation to trigger CTLA-4 expression. However comparative analysis of CTLA-4 trafficking in regulatory and conventional subsets has not been performed. METHODS: Here we assess CTLA-4 expression in antigen specific conventional and regulatory cells responding to immunizing antigen in vivo and analyse the membrane trafficking of CTLA-4 using an in vitro recycling assay. We assess the expression of CTLA-4 on Treg infiltrating the pancreas in the DO11*RIP-mOVA diabetes model and the role of CTLA-4 in Treg function. RESULTS: Regulatory T cells show an enhanced capacity to traffic CTLA-4 following stimulation compared with conventional T cells. Treg infiltrating the pancreas in DO11*RIP-mOVA mice show high expression of CTLA-4. Furthermore CTLA-4-deficient Treg fail to control diabetes in an adoptive transfer model of diabetes, even in situations where they outnumber the disease-inducing conventional T cells. CONCLUSIONS: These data show that not only do regulatory T cells express higher levels of intracellular CTLA-4 than conventional T cells, but they also show an increased capacity to traffic CTLA-4 to the cell surface following stimulation. CTLA-4 is strongly upregulated in regulatory T cells infiltrating the target tissue in a mouse model of type 1 diabetes and expression of this protein is critical for effective regulation. PMID- 22069291 TI - Pioglitazone may accelerate disease course of slowly progressive type 1 diabetes. AB - BACKGROUND: It has been reported that intervention with insulin in slowly progressive type 1 diabetic (SPIDDM) patients delays the progression to an insulin-dependent state compared to that with sulfonylureas. However, the rate of progression to SPIDDM with the use of insulin-sensitizing agents is unknown. The aim of this study was to determine the effect of insulin-sensitizing agents on SPIDDM patients. METHODS: The enrolled SPIDDM patients were randomly allocated to a pioglitazone or metformin group. When the haemoglobin A1C level was more than 8% on two consecutive occasions, the case was considered to reach the end point. RESULTS: By 4 years post-intervention, all patients had reached the end point in the pioglitazone group, whereas only 20% of patients had reached the end point in the metformin group (p<0.05). CONCLUSIONS: Pioglitazone may accelerate the disease course of SPIDDM. PMID- 22069292 TI - Prevention of type 1 diabetes by inducing subclinical dermatitis on a small area. AB - OBJECTIVE: We have previously epidemiologically shown that type 1 diabetes is inversely associated with contact allergy. This finding is intriguing as type 1 diabetes and contact allergy are two completely different diseases, although T cells are involved in both diseases. The objective of this study was therefore to experimentally study the effect of contact allergens on the development of diabetes in non-obese diabetic mice. METHODS: Non-obese diabetic mice 4 weeks of age were separated into seven groups. One group was exposed to tapped water every 14th day, whereas the remaining six groups were split into sensitizations groups or elicitation groups (exposure every 14th day). These groups were then treated with one of the selected contact allergens (PPD or DNCB) or vehicle (AOO). All groups received the sensitizing treatment regime, and hereafter only the elicitation groups were further treated. If the blood glucose reached 14 mM, the mice were considered diabetic and euthanized. Cardiac heart blood was drawn at euthanization, and a Luminex analysis was done on the serum. RESULTS: We showed that repeated application of a low dose of PPD reduced the incidence of diabetes compared to application with water (47% versus 93%, p=0.004). The rest of the groups developed diabetes with a cumulative incidence rate above 80%. The Luminex cytokine analysis revealed no differences between the groups, and no elevated cytokine level suggested a systemic response. Dermatitis was not noticeable by visual inspection, a histological examination, however, revealed a slight infiltration in the ears in the elicitation groups exposed to contact allergens. CONCLUSION: This study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in non-obese diabetic mice. The contact allergens gave a non-visible, subclinical dermatitis on the application site. Activation of NKT cells to the ear lymph nodes seems to be involved. PMID- 22069293 TI - Fulminant type 1 diabetes--an important subtype in East Asia. AB - Fulminant type 1 diabetes is defined as a subtype of type 1 diabetes with a remarkably acute onset. A nationwide survey identified that this variant accounts for approximately 20% of acute-onset type 1 diabetic patients in Japan. Recent studies indicate that this is not a minor subtype in other East Asian countries. As genetic factors, we revealed association of HLA-DR-DQ, HLA-B and CTLA-4 to fulminant type 1 diabetes. As an environmental factor, viral infection would contribute to the development of this subtype. Cellular infiltration to islets was detected soon after the onset but not observed 1 month after the onset. Macrophages and T cells were the main components of the infiltrates. Enterovirus RNA and Toll-like receptor-3 expression, a signature of viral infection, was also observed. These findings suggest that viral infection in the susceptible individual might trigger anti-viral immune response and that pancreatic beta cells are rapidly destroyed through the accelerated immune reaction. PMID- 22069294 TI - Pathological changes in the pancreas of fulminant type 1 diabetes and slowly progressive insulin-dependent diabetes mellitus (SPIDDM): innate immunity in fulminant type 1 diabetes and SPIDDM. AB - OBJECTIVE: The contribution of innate immunity responsible for beta-cell destruction in fulminant type 1 diabetes (FT1D) and slowly progressive insulin dependent diabetes mellitus (SPIDDM) is unclear. RESEARCH DESIGN AND METHODS: Islet-cell expression of Toll-like receptors (TLRs) including TLR3 and TLR4, the cytoplasmic retinoic acid-inducible protein I (RIG-I)-like helicases, RIG-I, melanoma differentiation-associated gene-5 and laboratory of genetics and physiology 2 in the affected islets were studied immuno-histochemically on three pancreases obtained 2-5 days after the onset of FT1D and a pancreas from a patient with SPIDDM. RESULTS: Laboratory of genetics and physiology 2 and RIG-I strongly expressed in beta cells in all three FT1D pancreases infected with enterovirus (VP1 antigen). Melanoma differentiation-associated gene-5 was hyper expressed in all subsets of islet cells including beta cells and alpha cells. TLR3 and TLR4 were expressed in mononuclear cells that infiltrated to islets. IFN alpha/beta was strongly expressed in islet cells. In contrast, pancreas of a patient with SPIDDM, enterovirus and expression of innate immune receptors including RIG-I, melanoma differentiation-associated gene-5, hyperexpression of laboratory of genetics and physiology 2 and mononuclear cells, which were positive for TLR3 and TLR4, and infiltration to the islets were not detected. CONCLUSIONS: These findings demonstrate that retinoic acid-inducible protein I (RIG-I)-like helicases and TLRs play a crucial role on beta-cell destruction in enterovirus-induced FT1D. The presence of distinct mechanism(s) of slowly progressive beta-cell failure in SPIDDM was suggested. PMID- 22069295 TI - Heterogeneity among patients with latent autoimmune diabetes in adults. AB - BACKGROUND: Some type 1 diabetic patients do not require insulin at diagnosis of diabetes, and they progress to insulin dependence only after several years (latent autoimmune diabetes in adults). However, not all patients with latent autoimmune diabetes in adults progress to insulin dependence. We compared the characteristics of patients with high glutamic acid decarboxylase antibodies (GADA) titres (>=10 U/mL) to those of patients with low titres and examined other factors possibly associated with the progression to insulin dependence. METHODS: We began registering diabetic patients in 1993 and have since followed them prospectively. Among these patients, we analysed clinical characteristics and progression to insulin dependence in those followed for more than 5 years. RESULTS: Patients with high GADA titres were younger and had lower body mass index, shorter disease durations and lower serum C-peptide (s-CPR) levels than the patients with low GADA titre and GADA negative type 2 diabetes. Frequencies of other islet-related autoantibodies were significantly higher in patients with high GADA titre than in those with low GADA titres. Disease protective HLA class II genotypes were less frequent in patients with high titre. The positive predictive value of being GADA positive was only 42.7%. The positive predictive value increased to 78.6% when the cut-off was set at the relatively high level of 10 U/mL. Combining GADA with other islet-related autoantibodies or HLA class II genotype increased positive predictive value but decreased sensitivity. CONCLUSIONS: Our results suggest that latent autoimmune diabetes in adults constitutes a heterogeneous group and that the majority of patients with high GADA titres (>=10 U/mL) will ultimately develop type 1 diabetes while those with low titres include patients with type 1 and type 2 diabetes. PMID- 22069296 TI - LADA prevalence estimation and insulin dependency during follow-up. AB - BACKGROUND: Latent autoimmune diabetes in adults (LADA) is a form of autoimmune mediated diabetes in adults, usually defined by GAD autoantibody positivity. Few epidemiological surveys on LADA in Asians did not come to a conclusive answer regarding prevalence and incidence, because of different criteria used in patient ascertainment. METHODS: We estimated LADA prevalence in a recent type 2 diabetes cohort by the positivity of circulating autoantibodies to pancreatic islet cell antigens (GAD, IA-2 and zinc transporter 8 (ZnT8)) applying a comparable Caucasian criteria. We then observed the development of insulin dependency prospectively for 36 months. RESULTS: Applying the European NIRAD LADA group criteria, we found a high prevalence of LADA (4.4%) in Korean patients with phenotypic type 2 diabetes. This high prevalence of LADA in Korea is noteworthy since the previous population-based LADA prevalence survey reported low prevalence (1.7%). When we consider the low-titre GAD antibodies and the low prevalence of multiple autoantibodies, however, increased LADA prevalence does not necessarily mean increase in future insulin dependency. After 36 months of follow-up, only 3 of 39 patients who were initially classified as LADA have become insulin-dependent. Those three were all positive for multiple autoantibodies (GAD, IA-2 and zinc transporter 8 antibody). Other features of insulin secretion or insulin resistance did not determine future insulin necessity. CONCLUSIONS: Although the LADA prevalence estimated by anti-GAD positivity appeared to increase, the true insulin dependency evidenced by multiple antibody positivity did not increase in Korea. PMID- 22069298 TI - Optical versus virtual: teaching assistant perceptions of the use of virtual microscopy in an undergraduate human anatomy course. AB - Many studies that evaluate the introduction of technology in the classroom focus on student performance and student evaluations. This study focuses on instructor evaluation of the introduction of virtual microscopy into an undergraduate anatomy class. Semi-structured interviews were conducted with graduate teaching assistants (TA) and analyzed through qualitative methods. This analysis showed that the teaching assistants found the virtual microscope to be an advantageous change in the classroom. They cite the ease of use of the virtual microscope, access to histology outside of designated laboratory time, and increasing student collaboration in class as the primary advantages. The teaching assistants also discuss principal areas where the use of the virtual microscope can be improved from a pedagogical standpoint, including requiring students to spend more time working on histology in class. PMID- 22069299 TI - Three-dimensional segmentation of nuclei and mitotic chromosomes for the study of cell divisions in live Drosophila embryos. AB - Drosophila embryogenesis is an established model to investigate mechanisms and genes related to cell divisions in an intact multicellular organism. Progression through the cell cycle phases can be monitored in vivo using fluorescently labeled fusion proteins and time-lapse microscopy. To measure cellular properties in microscopic images, accurate and fast image segmentation methods are a critical prerequisite. To quantify static and dynamic features of interphase nuclei and mitotic chromosomes, we developed a three-dimensional (3D) segmentation method based on multiple level sets. We tested our method on 3D time series images of live embryos expressing histone-2Av-green fluorescence protein. Our method is robust to low signal-to-noise ratios inherent to high-speed imaging, fluorescent signals in the cytoplasm, and dynamic changes of shape and texture. Comparisons with manual ground-truth segmentations showed that our method achieves more than 90% accuracy on the object as well as voxel levels and performs consistently throughout all cell cycle phases and developmental stages from syncytial blastoderm to postblastoderm mitotic domains. PMID- 22069300 TI - Pericytes: a universal adult tissue stem cell? PMID- 22069301 TI - Cell phones go cellular--current scale-down lab-in-your-pocket applications. PMID- 22069302 TI - Surface chemical immobilization of parylene C with thermosensitive block copolymer brushes based on N-isopropylacrylamide and N-tert-butylacrylamide: synthesis, characterization, and cell adhesion/detachment. AB - Poly(N-isopropylacrylamide) (pNIPAM), poly(N-tert-butylacrylamide) (pNTBAM), and their copolymer brushes were covalently immobilized onto parylene C (PC) surfaces via surface initiated atom transfer radical polymerization (ATRP). Contact angle measurement between 13 and 40 degrees C showed that the hydrophobicity of the modified PC surfaces was thermally sensitive. Among these samples, PC grafted with pNIPAM (PC-NI), PC grafted with pNTBAM (PC-NT) and PC grafted with copolymer brushes containing pNTBAM and pNIPAM (PC-NT-NI) exhibited the lower critical solution temperature (LCST) at 29, 22, and 24 degrees C, respectively. Cytocompatibility study for the modified surfaces was performed by 5 days human skin fibroblast culture at 37 degrees C. Data showed that only a very small amount of cells adhered on the PC and PC-NI surfaces, while a significantly higher amount of cell adhesion and growth was observed on PC-NT and PC-NT-NI surfaces. Furthermore, cell detachment at the temperatures of 24 and 6 degrees C were studied after the substrates were cultured with cells at 37 degrees C for 24 h. The results showed that the cells on PC-NI formed the aggregations and loosely attached on the substrate after 30-min culture at 24 degrees C, while no significant cell detachment was observed for PC-NT and PC-NT-NI samples at this temperature. By continuing the cell culture for additional 100 min at 6 degrees C for PC-NT and PC-NT-NI, about 10 and 35% of the cells were found detached respectively, and the unattached cells aggregated on the substrate. In comparison, cells cultured on the tissue culture petri dish (TCP) exhibited no quantity and morphology changes at the culture temperatures of 37, 24, and 6 degrees C. This study showed that: (1) immobilization of PC with nonthermal sensitive pNTBAM could provide PC surface thermal sensitive hydrophilicity; (2) the chlorines on the polymer brushes of PC-NT could be used to further initiate the ATRP pNIPAM and form block copolymer brushes; (3) the incorporation of pNTBAM into pNIPAM on PC-NT-NI could change the surface thermal hydrophilicity property, and be further applied to decrease the LCST of the modified PC surface; (4) grafted pNIPAM brushes on PC-NI by ATRP showed very low cell adhesion and proliferation in 5 days fibroblast culture at 37 degrees C, and cell detached at 24 degrees C; (5) the incorporation of pNTBAM into pNIPAM on PC-NT-NI decreased the thermal sensitivity of cell adhesion/detachment, cell detached at 6 degrees C, but the cell adhesion and proliferation were significantly improved at a wide temperature range. PMID- 22069303 TI - Lamellar stack formation and degradative behaviors of hydrolytically degraded poly(epsilon-caprolactone) and poly(glycolide-epsilon-caprolactone) blended fibers. AB - Electrospun fibrous mats have gained popularity in bioengineering over the past decade, but few papers detail their degradative mechanisms. To address this, blends of hydrophobic poly(epsilon-caprolactone) (PCL) and hydrophilic PGA-PCL PGA triblock copolymer were electrospun into aligned fibrous mats to assess the copolymers' mechanical and degradative properties. Increased hydrophilic triblock content led to enhanced morphological uniformity of fiber, tightening of fiber diameters, increased storage and Young's modulus, and decreased elongation. The corresponding decrease in hydrophobic PCL content led to faster hydrolytic degradation rate, as reflected by enhanced decrease in mass, molecular weight, and modulus loss at 25, 37, and 45 degrees C. The activation energy for hydrolytic degradation for 15:85 PCL: triblock copolymer was approximately half that of 85:15 PCL: triblock copolymer. Detailed examination of fiber morphology and crystallinity revealed initial surface erosion followed by the evolution of crystalline lamellar stacks and bulk degradation at 37 degrees C. Because of the high surface to volume and short diffusion length scale of the small diameter fibers, surface and bulk degradation may both contribute to the hydrolytic degradative behavior of these electrospun fibrous mats. Electrospun mats' distinct architecture that embodies high specific surface to volume and interfiber porous ultrastructures that lead to their unique degradative behaviors hold much potential for significant impact in the field of tissue engineering and controlled drug delivery. PMID- 22069304 TI - Hospitalists and intensivists in the medical ICU: a prospective observational study comparing mortality and length of stay between two staffing models. AB - BACKGROUND: A shortage of critical care specialists or intensivists, coupled with expanding United States critical care needs, mandates identification of alternate qualified physicians for intensive care unit (ICU) staffing. OBJECTIVE: To compare mortality and length of stay (LOS) of medical ICU patients cared for by a hospitalist or an intensivist-led team. DESIGN: Prospective observational study. SETTING: Urban academic community hospital affiliated with a major regional academic university. PATIENTS: Consecutive medical patients admitted to a hospitalist ICU team (n = 828) with selective intensivist consultation or an intensivist-led ICU teaching team (n = 528). MEASUREMENTS: Endpoints were ICU and in-hospital mortality and LOS, adjusted for patient differences with logistic and linear regression models and propensity scores. RESULTS: The odds ratio adjusted for disease severity for in-hospital mortality was 0.8 (95% confidence interval [CI]: 0.49, 1.18; P = 0.23) and ICU mortality was 0.8 (95% CI: 0.51, 1.32; P = 0.41), referent to the hospitalist team. The adjusted LOS was similar between teams (hospital LOS difference 0.9 days, P = 0.98; ICU LOS difference 0.3 days, P = 0.32). Mechanically ventilated patients with intermediate illness severity had lower hospital LOS (10.6 vs 17.8 days, P < 0.001) and ICU LOS (7.2 vs 10.6 days, P = 0.02), and a trend towards decreased in-hospital mortality (15.6% vs 27.5%, P = 0.10) in the intensivist-led group. CONCLUSIONS: The adjusted mortality and LOS demonstrated no statistically significant difference between hospitalist and intensivist-led ICU models. Mechanically ventilated patients with intermediate illness severity showed improved LOS and a trend towards improved mortality when cared for by an intensivist-led ICU teaching team. PMID- 22069305 TI - Multifunctional mesoporous silica nanospheres with cleavable Gd(III) chelates as MRI contrast agents: synthesis, characterization, target-specificity, and renal clearance. AB - Mesoporous silica nanospheres (MSNs) are a promising material for magnetic resonance imaging (MRI) contrast agents. In this paper multifunctional MSNs with cleavable Gd(III) chelates are synthesized and characterized, and their applicability as MRI contrast agents is demonstrated both in vitro and in vivo. The MSNs contain Gd(III) chelates that are covalently linked via a redox responsive disulfide moiety. The MSNs are further functionalized with polyethylene glycol (PEG) and an anisamide ligand to improve their biocompatibility and target specificity. The effectiveness of MSNs as an MRI imaging contrast agent and their targeting ability are successfully demonstrated in vitro using human colon adenocarcinoma and pancreatic cancer cells. Finally, the capability of this platform as an in vivo MRI contrast agent is tested using a 3T scanner. The Gd(III) chelate was quickly cleaved by the blood pool thiols and eliminated through the renal excretion pathway. Further tuning of the Gd(III) chelate release kinetics is needed before the MSN system can be used as target specific MRI contrast agents in vivo. PMID- 22069306 TI - Self-assembly of graphenelike ZnO superstructured nanosheets and their application in hybrid photoconductors. AB - Photoconductors require high charge-carrier mobilities, sensitivity over a wide range of light levels, and good stability. Combining an organic semiconductor with environmentally benign inorganic nanoparticles is a rational means to develop photoconductors with such properties. However, an inhomogeneous distribution of nanoparticles in the active layer restricts both charge-carrier mobility and charge collection at an electrode. In this paper, ultrathin ZnO superstructured nanosheets are successfully synthesized by a solvothermal method. Time-dependent investigations show that the superstructured nanosheets assemble in solution during the growth process. Given that high-quality ZnO nanosheets are obtained, a hybrid photoconductor device with P3HT is fabricated and investigated. Sensitivity above 200% under simulated sunlight is obtained with good air stability. This study demonstrates a general approach to design photoconductors using hybrid nanomaterials. PMID- 22069307 TI - Recommendations for mass spectrometry data quality metrics for open access data (corollary to the Amsterdam principles). AB - Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the U.S. National Cancer Institute (NCI) convened the "International Workshop on Proteomic Data Quality Metrics" in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed upon two primary needs for the wide use of quality metrics: (i) an evolving list of comprehensive quality metrics and (ii) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data. By agreement, this article is published simultaneously in Proteomics, Proteomics Clinical Applications, Journal of Proteome Research, and Molecular and Cellular Proteomics, as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals. PMID- 22069308 TI - A novel role for interleukin-27 (IL-27) as mediator of intestinal epithelial barrier protection mediated via differential signal transducer and activator of transcription (STAT) protein signaling and induction of antibacterial and anti inflammatory proteins. AB - The role of the Th17 cell inhibiting cytokine IL-27 in the pathogenesis of inflammatory bowel disease is contradictory. Its effects on the intestinal barrier have so far not been investigated, which was the aim of this study. We show that intestinal epithelial cells (IEC) express both IL-27 receptor subunits IL-27RA and gp130. The IL-27 receptor expression is up-regulated in intestinal inflammation and during bacterial infection. IL-27 activates ERK and p38 MAPKs as well as Akt, STAT1, STAT3, and STAT6 in IEC. IL-27 significantly enhances cell proliferation and IEC restitution. These functions of IL-27 are dependent on the activation of STAT3 and STAT6 signaling pathways. As analyzed by microarray, IL 27 modulates the expression of 428 target genes in IEC (316 up and 112 down; p<0.05). IL-27 as well as its main target genes are up-regulated in colonic tissue and IEC isolated from mice with dextran sulfate sodium (DSS)-induced colitis. The IL-27-induced expression of the anti-bacterial gene deleted in malignant brain tumor 1 (DMBT1) is mediated by p38 and STAT3 signaling, whereas the activation of the anti-inflammatory and anti-bacterial gene indoleamine 2,3 dioxygenase (IDO1) is dependent on STAT1 signal transduction. IL-27-induced indoleamine 2,3-dioxygenase enzymatic activity leads to growth inhibition of intestinal bacteria by causing local tryptophan depletion. For the first time, we characterize IL-27 as a mediator of intestinal epithelial barrier protection mediated via transcriptional activation of anti-inflammatory and antibacterial target genes. PMID- 22069309 TI - Molecular basis of maillard amide-advanced glycation end product (AGE) formation in vivo. AB - The Maillard reaction in vivo entails alteration of proteins or free amino acids by non-enzymatic glycation or glycoxidation. The resulting modifications are called advanced glycation end products (AGEs) and play a prominent role in various pathologies, including normoglycemic uremia. Recently, we established a new class of lysine amide modifications in vitro. Now, human plasma levels of the novel amide-AGEs N(6)-acetyl lysine, N(6)-formyl lysine, N(6)-lactoyl lysine, and N(6)-glycerinyl lysine were determined by means of LC-MS/MS. They were significantly higher in uremic patients undergoing hemodialysis than in healthy subjects. Model reactions with N(1)-t-butoxycarbonyl-lysine under physiological conditions confirmed 1-deoxy-d-erythro-hexo-2,3-diulose as an immediate precursor. Because formation of N(6)-formyl lysine from glucose responded considerably to the presence of oxygen, glucosone was identified as another precursor. Comparison of the in vivo results with the model experiments enabled us to elucidate possible formation pathways linked to Maillard chemistry. The results strongly suggest a major participation of non-enzymatic Maillard mechanisms on amide-AGE formation pathways in vivo, which, in the case of N(6) acetyl lysine, parallels enzymatic processes. PMID- 22069310 TI - Ephrinb1 and Ephrinb2 are associated with interleukin-7 receptor alpha and retard its internalization from the cell surface. AB - IL-7 plays vital roles in thymocyte development, T cell homeostasis, and the survival of these cells. IL-7 receptor alpha (IL-7Ralpha) on thymocytes and T cells is rapidly internalized upon IL-7 ligation. Ephrins (Efns) are cell surface molecules and ligands of the largest receptor kinase family, Eph kinases. We discovered that T cell-specific double gene knock-out (dKO) of Efnb1 and Efnb2 in mice led to reduced IL-7Ralpha expression in thymocytes and T cells, and that IL 7Ralpha down-regulation was accelerated in dKO CD4 cells upon IL-7 treatment. On the other hand, Efnb1 and Efnb2 overexpression on T cell lymphoma EL4 cells retarded IL-7Ralpha down-regulation. dKO T cells manifested compromised STAT5 activation and homeostatic proliferation, an IL-7-dependent process. Fluorescence resonance energy transfer and immunoprecipitation demonstrated that Efnb1 and Efnb2 interacted physically with IL-7Ralpha. Such interaction likely retarded IL 7Ralpha internalization, as Efnb1 and Efnb2 were not internalized. Therefore, we revealed a novel function of Efnb1 and Efnb2 in stabilizing IL-7Ralpha expression at the post-translational level, and a previously unknown modus operandi of Efnbs in the regulation of expression of other vital cell surface receptors. PMID- 22069311 TI - The mycobacterial transcriptional regulator whiB7 gene links redox homeostasis and intrinsic antibiotic resistance. AB - Intrinsic drug resistance in Mycobacterium tuberculosis limits therapeutic options for treating tuberculosis. The mycobacterial transcriptional regulator whiB7 contributes to intrinsic resistance by activating its own expression and many drug resistance genes in response to antibiotics. To investigate whiB7 activation, we constructed a GFP reporter to monitor its expression, and we used it to investigate the whiB7 promoter and to screen our custom library of almost 600 bioactive compounds, including the majority of clinical antibiotics. Results showed whiB7 was transcribed from a promoter that was conserved across mycobacteria and other actinomycetes, including an AT-rich sequence that was likely targeted by WhiB7. Expression was induced by compounds having diverse structures and targets, independent of the ability of whiB7 to mediate resistance, and was dependent on media composition. Pretreatment with whiB7 activators resulted in clinically relevant increases in intrinsic drug resistance. Antibiotic-induced transcription was synergistically increased by the reductant dithiothreitol, an effect mirrored by a whiB7-dependent shift to a highly reduced cytoplasm reflected by the ratio of reduced/oxidized mycothiol. These data provided evidence that intrinsic resistance resulting from whiB7 activation is linked to fundamental changes in cell metabolism. PMID- 22069313 TI - Anchor peptide of transferrin-binding protein B is required for interaction with transferrin-binding protein A. AB - Gram-negative bacterial pathogens belonging to the Pasteurellaceae, Moraxellaceae, and Neisseriaceae families rely on an iron acquisition system that acquires iron directly from host transferrin (Tf). The process is mediated by a surface receptor composed of transferrin-binding proteins A and B (TbpA and TbpB). TbpA is an integral outer membrane protein that functions as a gated channel for the passage of iron into the periplasm. TbpB is a surface-exposed lipoprotein that facilitates the iron uptake process. In this study, we demonstrate that the region encompassing amino acids 7-40 of Actinobacillus pleuropneumoniae TbpB is required for forming a complex with TbpA and that the formation of the complex requires the presence of porcine Tf. These results are consistent with a model in which TbpB is responsible for the initial capture of iron-loaded Tf and subsequently interacts with TbpA through the anchor peptide. We propose that TonB binding to TbpA initiates the formation of the TbpB-TbpA complex and transfer of Tf to TbpA. PMID- 22069312 TI - Functional selective oxytocin-derived agonists discriminate between individual G protein family subtypes. AB - We used a bioluminescence resonance energy transfer biosensor to screen for functional selective ligands of the human oxytocin (OT) receptor. We demonstrated that OT promoted the direct engagement and activation of G(q) and all the G(i/o) subtypes at the OT receptor. Other peptidic analogues, chosen because of specific substitutions in key OT structural/functional residues, all showed biased activation of G protein subtypes. No ligand, except OT, activated G(oA) or G(oB), and, with only one exception, all of the peptides that activated G(q) also activated G(i2) and G(i3) but not G(i1), G(oA), or G(oB), indicating a strong bias toward these subunits. Two peptides (DNalOVT and atosiban) activated only G(i1) or G(i3), failed to recruit beta-arrestins, and did not induce receptor internalization, providing the first clear examples of ligands differentiating individual G(i/o) family members. Both analogs inhibited cell proliferation, showing that a single G(i) subtype-mediated pathway is sufficient to prompt this physiological response. These analogs represent unique tools for examining the contribution of G(i/o) members in complex biological responses and open the way to the development of drugs with peculiar selectivity profiles. This is of particular relevance because OT has been shown to improve symptoms in neurodevelopmental and psychiatric disorders characterized by abnormal social behaviors, such as autism. Functional selective ligands, activating a specific G protein signaling pathway, may possess a higher efficacy and specificity on OT based therapeutics. PMID- 22069314 TI - Site-directed mutagenesis reveals key residue for O antigen chain length regulation and protein stability in Pseudomonas aeruginosa Wzz2. AB - The production of preferred lipopolysaccharide O antigen chain lengths is important for the survival of pathogenic Gram-negative bacteria in different environments, yet how Wzz proteins regulate these lengths is not well understood. The Wzz2 proteins from two different serotype O11 Pseudomonas aeruginosa strains are responsible for the expression of different very long chain lengths despite high sequence homology. Site-directed mutagenesis was performed to determine whether a specific amino acid was responsible for this difference in chain length; the residue present in position 321 within the second predicted coiled coil region was able to determine which chain length was produced. A panel of site-directed mutants introducing different amino acids at this position implicated that the charge of the amino acid affected chain length, with positively charged residues associated with shorter chain lengths. Expression data also suggested this site was important for overall stability of the protein because mutants predicted to disrupt proper folding of the alpha helix led to lower protein levels. Cross-linking studies found that Wzz2 proteins producing shorter chain lengths had more stable higher-order oligomers. Mapping residue 321 onto the solved Escherichia coli Wzz FepE crystal structure predicted it to be located within alpha helix 8, which participates in intermonomeric interactions. These data further support the observation that Wzz oligomerization is necessary for chain length regulating activity but also provide evidence that differences in complex stability or changes in the conformation of the oligomer can lead to shifts in the length of the O antigen side chain. PMID- 22069315 TI - The membrane-proximal intracellular domain of the epidermal growth factor receptor underlies negative cooperativity in ligand binding. AB - The binding of EGF induces dimerization of its receptor, leading to the stimulation of its intracellular tyrosine kinase activity. Kinase activation occurs within the context of an asymmetric dimer in which one kinase domain serves as the activator for the other kinase domain but is not itself activated. How ligand binding is related to the formation and dynamics of this asymmetric dimer is not known. The binding of EGF to its receptor is negatively cooperative- that is, EGF binds with lower affinity to the second site on the dimer than to the first site on the dimer. In this study, we analyzed the binding of (125)I-EGF to a series of EGF receptor mutants in the intracellular juxtamembrane domain and demonstrate that the most membrane-proximal portion of this region plays a significant role in the genesis of negative cooperativity in the EGF receptor. The data are consistent with a model in which the binding of EGF to the first site on the dimer induces the formation of one asymmetric kinase dimer. The binding of EGF to the second site is required to disrupt the initial asymmetric dimer and allow the formation of the reciprocal asymmetric dimer. Thus, some of the energy of binding to the second site is used to reorient the first asymmetric dimer, leading to a lower binding affinity and the observed negative cooperativity. PMID- 22069316 TI - Alternative splicing at C terminus of Ca(V)1.4 calcium channel modulates calcium dependent inactivation, activation potential, and current density. AB - The Ca(V)1.4 voltage-gated calcium channel is predominantly expressed in the retina, and mutations to this channel have been associated with human congenital stationary night blindness type-2. The L-type Ca(V)1.4 channel displays distinct properties such as absence of calcium-dependent inactivation (CDI) and slow voltage-dependent inactivation (VDI) due to the presence of an autoinhibitory domain (inhibitor of CDI) in the distal C terminus. We hypothesized that native Ca(V)1.4 is subjected to extensive alternative splicing, much like the other voltage-gated calcium channels, and employed the transcript scanning method to identify alternatively spliced exons within the Ca(V)1.4 transcripts isolated from the human retina. In total, we identified 19 alternative splice variations, of which 16 variations have not been previously reported. Characterization of the C terminus alternatively spliced exons using whole-cell patch clamp electrophysiology revealed a splice variant that exhibits robust CDI. This splice variant arose from the splicing of a novel alternate exon (43*) that can be found in 13.6% of the full-length transcripts screened. Inclusion of exon 43* inserts a stop codon that truncates half the C terminus. The Ca(V)1.4 43* channel exhibited robust CDI, a larger current density, a hyperpolarized shift in activation potential by ~10 mV, and a slower VDI. Through deletional experiments, we showed that the inhibitor of CDI was responsible for modulating channel activation and VDI, in addition to CDI. Calcium currents in the photoreceptors were observed to exhibit CDI and are more negatively activated as compared with currents elicited from heterologously expressed full-length Ca(V)1.4. Naturally occurring alternative splice variants may in part contribute to the properties of the native Ca(V)1.4 channels. PMID- 22069317 TI - 4-Phenylbutyrate stimulates Hsp70 expression through the Elp2 component of elongator and STAT-3 in cystic fibrosis epithelial cells. AB - Sodium 4-phenylbutyrate (4PBA) corrects trafficking of DeltaF508-CFTR in Cystic Fibrosis (CF) epithelia, which is hypothesized to, at least in part, result from increased expression of Hsp70 (stress-induced 70 kDa heat shock protein). To identify other 4PBA-regulated proteins that may promote correction of DeltaF508 trafficking, we performed differential display RT-PCR on mRNA from IB3-1 CF bronchiolar epithelial cells treated for 0-24 h with 1 mM 4PBA. In this screen, a STAT-3 (signal transducer and activator of transcription-3)-interacting protein, StIP-1 that regulates STAT-3 activation had transiently increased expression. StIP-1 is identical to Elongator protein 2 (Elp2), a component of the Elongator complex that regulates RNA polymerase II. Previous studies have suggested that Elongator regulates Hsp70 mRNA transcription, and that the Hsp70 promoter contains functional STAT-3-binding sites. We therefore tested the hypothesis that 4PBA increases Hsp70 expression by an Elongator- and STAT-3-dependent mechanism. 4PBA treatment of IB3-1 CF bronchiolar epithelial cells caused transiently increased expression of Hsp70 protein, as well as Elp2 protein and mRNA. Elp2 depletion by transfection of small interfering RNAs, reduced both Elp2 and Hsp70 protein expression. 4PBA also caused transient activation of STAT-3, and increased abundance of nuclear proteins that bind to the STAT-3-responsive element of the Hsp70 promoter. Luciferase reporter assays demonstrated that both Elp2 overexpression and 4PBA increase Hsp70 promoter activity, while Elp2 depletion blocked the ability of 4PBA to stimulate Hsp70 promoter activity. Together, these data suggest that Elp2 and STAT-3 mediate, at least in part, the stimulation of Hsp70 expression by 4PBA. PMID- 22069318 TI - Polyubiquitination of transforming growth factor beta (TGFbeta)-associated kinase 1 mediates nuclear factor-kappaB activation in response to different inflammatory stimuli. AB - The transcription factor nuclear factor kappaB (NF-kappaB) plays a central role in regulating inflammation in response to several external signals. The TGFbeta associated kinase 1 (TAK1) is an upstream regulator of NF-kappaB signaling. In TGFbeta-stimulated cells, TAK1 undergoes Lys-63-linked polyubiquitination at Lys 34 by TNF receptor-associated factor 6 and is thereby activated. The aim of this study was to investigate whether TAK1 polyubiquitination at Lys-34 is also essential for NF-kappaB activation via TNF receptor, IL-1 receptor and toll-like receptor 4. We observed that TAK1 polyubiquitination occurred at Lys-34 and required the E3 ubiquitin ligase TNF receptor-associated factor 6 after stimulation of cells with IL-1beta. Polyubiquitination of TAK1 also occurred at Lys-34 in cells stimulated by TNF-alpha and LPS, which activates TLR4, as well as in HepG2 and prostate cancer cells stimulated with TGFbeta, which in all cases resulted in NF-kappaB activation. Expression of a K34R-mutant TAK1 led to a reduced NF-kappaB activation, IL-6 promoter activity, and proinflammatory cytokine secretion by TNF-alpha-stimulated PC-3U cells. Similar results were obtained in the mouse macrophage cell line RAW264.7 after LPS treatment. In conclusion, polyubiquitination of TAK1 is correlated with activation of TAK1 and is essential for activation of NF-kappaB signaling downstream of several receptors. PMID- 22069319 TI - Interferon-gamma alters downstream signaling originating from epidermal growth factor receptor in intestinal epithelial cells: functional consequences for ion transport. AB - The epidermal growth factor receptor (EGFr) regulates many cellular functions, such as proliferation, apoptosis, and ion transport. Our aim was to investigate whether long term treatment with interferon-gamma (IFN-gamma) modulates EGF activation of downstream signaling pathways in intestinal epithelial cells and if this contributes to dysregulation of epithelial ion transport in inflammation. Polarized monolayers of T(84) and HT29/cl.19A colonocytes were preincubated with IFN-gamma prior to stimulation with EGF. Basolateral potassium transport was studied in Ussing chambers. We also studied inflamed colonic mucosae from C57BL/6 mice treated with dextran sulfate sodium or mdr1a knock-out mice and controls. IFN-gamma increased intestinal epithelial EGFr expression without increasing its phosphorylation. Conversely, IFN-gamma caused a significant decrease in EGF stimulated phosphorylation of specific EGFr tyrosine residues and activation of ERK but not Akt-1. In IFNgamma-pretreated cells, the inhibitory effect of EGF on carbachol-stimulated K(+) channel activity was lost. In inflamed colonic tissues, EGFr expression was significantly increased, whereas ERK phosphorylation was reduced. Thus, although it up-regulates EGFr expression, IFN-gamma causes defective EGFr activation in colonic epithelial cells via reduced phosphorylation of specific EGFr tyrosine residues. This probably accounts for altered downstream signaling consequences. These observations were corroborated in the setting of colitis. IFN-gamma also abrogates the ability of EGF to inhibit carbachol stimulated basolateral K(+) currents. Our data suggest that, in the setting of inflammation, the biological effect of EGF, including the inhibitory effect of EGF on Ca(2+)-dependent ion transport, is altered, perhaps contributing to diarrheal and other symptoms in vivo. PMID- 22069320 TI - Evidence against cellular internalization in vivo of NMO-IgG, aquaporin-4, and excitatory amino acid transporter 2 in neuromyelitis optica. AB - Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are thought to be pathogenic in neuromyelitis optica (NMO). Prior work has suggested that a key component of NMO autoantibody (NMO-IgG) pathogenesis is internalization of AQP4 and the associated glutamate transporter EAAT2, leading to glutamate excitotoxicity. Here, we show selective endocytosis of NMO-IgG and AQP4 in transfected cell cultures, but little internalization in brain in vivo. AQP4 dependent endocytosis of NMO-IgG occurred rapidly in various AQP4-transfected cell lines, with efficient transport from early endosomes to lysosomes. Cell surface AQP4 was also reduced following NMO-IgG exposure. However, little or no internalization of NMO-IgG, AQP4, or EAAT2 was found in primary astrocyte cultures, nor was glutamate uptake affected by NMO-IgG exposure. Following injection of NMO-IgG into mouse brain, NMO-IgG binding and AQP4 expression showed a perivascular astrocyte distribution, without detectable cellular internalization over 24 h. We conclude that astrocyte endocytosis of NMO-IgG, AQP4, and EAAT2 is not a significant consequence of AQP4 autoantibody in vivo, challenging generally accepted views about NMO pathogenesis. PMID- 22069321 TI - Protein aggregates are recruited to aggresome by histone deacetylase 6 via unanchored ubiquitin C termini. AB - The aggresome pathway is activated when proteasomal clearance of misfolded proteins is hindered. Misfolded polyubiquitinated protein aggregates are recruited and transported to the aggresome via the microtubule network by a protein complex consisting of histone deacetylase 6 (HDAC6) and the dynein motor complex. The current model suggests that HDAC6 recognizes protein aggregates by binding directly to polyubiquitinated proteins. Here, we show that there are substantial amounts of unanchored ubiquitin in protein aggregates with solvent accessible C termini. The ubiquitin-binding domain (ZnF-UBP) of HDAC6 binds exclusively to the unanchored C-terminal diglycine motif of ubiquitin instead of conjugated polyubiquitin. The unanchored ubiquitin C termini in the aggregates are generated in situ by aggregate-associated deubiquitinase ataxin-3. These results provide structural and mechanistic bases for the role of HDAC6 in aggresome formation and further suggest a novel ubiquitin-mediated signaling pathway, where the exposure of ubiquitin C termini within protein aggregates enables HDAC6 recognition and transport to the aggresome. PMID- 22069322 TI - Functional analysis of C-type lysozyme in penaeid shrimp. AB - Lysozyme is an enzyme that cleaves the beta-1,4-glycosidic linkages between N acetylmuramic acid and N-acetylglucosamine in peptidoglycan, leading to bacterial lysis. Recently, lysozyme has been found to have anti-HIV and anti-cancer properties in mammals. However, most functional analyses were done in vitro using purified or recombinant lysozyme protein. Here, we used RNA interference to silence c-type lysozyme expression in penaeid shrimp, Marsupenaeus japonicus, to analyze the function of lysozyme in vivo. Silencing of lysozyme expression by dsRNA lysozyme (dsLYZ) led to 100% mortality without any artificial bacterial infection in 5 days. Lysozyme deficiency caused the number of hemocytes in hemolymph to decrease from 1.3 * 10(7) to 2.3 * 10(6) cells/ml and caused the number of bacteria to increase from 78 to 764 colony-forming units/ml. Suppression of bacterial growth using oxytetracycline and kanamycin showed improvement in mortality, suggesting that shrimp mortality post- dsLYZ injection can be attributed to bacterial growth in the shrimp hemolymph. The majority of the bacteria, identified by 16 S rRNA analysis, were Gram-negative species such as Vibrio and Pseudomonas. Furthermore, PKH26 staining showed that the dsLYZ injected shrimp were unable to eliminate non pathogenic Escherichia coli or Staphylococcus aureus in 24 h. These data suggest that c-type lysozyme in shrimp serves to regulate the growth of bacterial communities, particularly Gram negative bacteria, in the hemolymph. PMID- 22069323 TI - Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobial peptide LL-37 in human mast cells: resistance to receptor phosphorylation, desensitization, and internalization. AB - Human LL-37 is a multifunctional antimicrobial peptide that promotes inflammation, angiogenesis, wound healing, and tumor metastasis. Most effects of LL-37 are mediated via the activation of the cell surface G protein-coupled receptor FPR2 on leukocytes and endothelial cells. Although LL-37 induces chemotaxis, degranulation, and chemokine production in mast cells, the receptor involved and the mechanism of its regulation remain unknown. MrgX2 is a member of Mas-related genes that is primarily expressed in human dorsal root ganglia and mast cells. We found that a human mast cell line LAD2 and CD34(+) cell-derived primary mast cells, which natively express MrgX2, responded to LL-37 for sustained Ca(2+) mobilization and substantial degranulation. However, an immature human mast cell line, HMC-1, that lacks functional MrgX2 did not respond to LL 37. shRNA-mediated knockdown of MrgX2 in LAD2 mast cell line and primary CD34(+) cell-derived mast cells caused a substantial reduction in LL-37-induced degranulation. Furthermore, mast cell lines stably expressing MrgX2 responded to LL-37 for chemotaxis, degranulation, and CCL4 production. Surprisingly, MrgX2 was resistant to LL-37-induced phosphorylation, desensitization, and internalization. In addition, shRNA-mediated knockdown of the G protein-coupled receptor kinases (GRK2 and GRK3) had no effect on LL-37-induced mast cell degranulation. This study identified MrgX2 as a novel G protein-coupled receptor for the antibacterial peptide LL-37 and demonstrated that unlike most G protein-coupled receptors it is resistant to agonist-induced receptor phosphorylation, desensitization, and internalization. PMID- 22069324 TI - Divergence and convergence in enzyme evolution. AB - Comparative analysis of the sequences of enzymes encoded in a variety of prokaryotic and eukaryotic genomes reveals convergence and divergence at several levels. Functional convergence can be inferred when structurally distinct and hence non-homologous enzymes show the ability to catalyze the same biochemical reaction. In contrast, as a result of functional diversification, many structurally similar enzyme molecules act on substantially distinct substrates and catalyze diverse biochemical reactions. Here, we present updates on the ATP grasp, alkaline phosphatase, cupin, HD hydrolase, and N-terminal nucleophile (Ntn) hydrolase enzyme superfamilies and discuss the patterns of sequence and structural conservation and diversity within these superfamilies. Typically, enzymes within a superfamily possess common sequence motifs and key active site residues, as well as (predicted) reaction mechanisms. These observations suggest that the strained conformation (the entatic state) of the active site, which is responsible for the substrate binding and formation of the transition complex, tends to be conserved within enzyme superfamilies. The subsequent fate of the transition complex is not necessarily conserved and depends on the details of the structures of the enzyme and the substrate. This variability of reaction outcomes limits the ability of sequence analysis to predict the exact enzymatic activities of newly sequenced gene products. Nevertheless, sequence-based (super)family assignments and generic functional predictions, even if imprecise, provide valuable leads for experimental studies and remain the best approach to the functional annotation of uncharacterized proteins from new genomes. PMID- 22069325 TI - Inference of functional properties from large-scale analysis of enzyme superfamilies. AB - As increasingly large amounts of data from genome and other sequencing projects become available, new approaches are needed to determine the functions of the proteins these genes encode. We show how large-scale computational analysis can help to address this challenge by linking functional information to sequence and structural similarities using protein similarity networks. Network analyses using three functionally diverse enzyme superfamilies illustrate the use of these approaches for facile updating and comparison of available structures for a large superfamily, for creation of functional hypotheses for metagenomic sequences, and to summarize the limits of our functional knowledge about even well studied superfamilies. PMID- 22069326 TI - Divergent evolution in enolase superfamily: strategies for assigning functions. AB - Nature's strategies for evolving catalytic functions can be deciphered from the information contained in the rapidly expanding protein sequence databases. However, the functions of many proteins in the protein sequence and structure databases are either uncertain (too divergent to assign function based on homology) or unknown (no homologs), thereby limiting the utility of the databases. The mechanistically diverse enolase superfamily is a paradigm for understanding the structural bases for evolution of enzymatic function. We describe strategies for assigning functions to members of the enolase superfamily that should be applicable to other superfamilies. PMID- 22069327 TI - Direct interaction between scaffolding proteins RACK1 and 14-3-3zeta regulates brain-derived neurotrophic factor (BDNF) transcription. AB - RACK1 is a scaffolding protein that spatially and temporally regulates numerous signaling cascades. We previously found that activation of the cAMP signaling pathway induces the translocation of RACK1 to the nucleus. We further showed that nuclear RACK1 is required to promote the transcription of the brain-derived neurotrophic factor (BDNF). Here, we set out to elucidate the mechanism underlying cAMP-dependent RACK1 nuclear translocation and BDNF transcription. We identified the scaffolding protein 14-3-3zeta as a direct binding partner of RACK1. Moreover, we found that 14-3-3zeta was necessary for the cAMP-dependent translocation of RACK1 to the nucleus. We further observed that the disruption of RACK1/14-3-3zeta interaction with a peptide derived from the RACK1/14-3-3zeta binding site or shRNA-mediated 14-3-3zeta knockdown inhibited cAMP induction of BDNF transcription. Together, these data reveal that the function of nuclear RACK1 is mediated through its interaction with 14-3-3zeta. As RACK1 and 14-3 3zeta are two multifunctional scaffolding proteins that coordinate a wide variety of signaling events, their interaction is likely to regulate other essential cellular functions. PMID- 22069328 TI - Thematic minireview series on enzyme evolution in the post-genomic era. AB - The emergence of genomics; ongoing computational advances; and the development of large-scale sequence, structural, and functional databases have created important new interdisciplinary linkages between molecular evolution, molecular biology, and enzymology. The five minireviews in this series survey advances and challenges in this burgeoning field from complementary perspectives. The series has three major themes. The first is the evolution of enzyme superfamilies, in which members exhibit increasing sequence, structural, and functional divergence with increasing time of divergence from a common ancestor. The second is the evolutionary role of promiscuous enzymes, which, in addition to their primary function, have adventitious secondary activities that frequently provide the starting point for the evolution of new enzymes. The third is the importance of in silico approaches to the daunting challenge of assigning and predicting the functions of the many uncharacterized proteins in the large-scale sequence and structural databases that are now available. A recent computational advance, the use of protein similarity networks that map functional data onto proteins clustered by similarity, is presented as an approach that can improve functional insight and inference. The three themes are illustrated with several examples of enzyme superfamilies, including the amidohydrolase, metallo-beta-lactamase, and enolase superfamilies. PMID- 22069329 TI - Divergence and convergence in enzyme evolution: parallel evolution of paraoxonases from quorum-quenching lactonases. AB - We discuss the basic features of divergent versus convergent evolution and of the common scenario of parallel evolution. The example of quorum-quenching lactonases is subsequently described. Three different quorum-quenching lactonase families are known, and they belong to three different superfamilies. Their key active site architectures have converged and are strikingly similar. Curiously, a promiscuous organophosphate hydrolase activity is observed in all three families. We describe the structural and mechanistic features that underline this converged promiscuity and how this promiscuity drove the parallel divergence of organophosphate hydrolases within these lactonase families by either natural or laboratory evolution. PMID- 22069330 TI - Toward a systems biology perspective on enzyme evolution. AB - Large superfamilies of enzymes derived from a common progenitor have emerged by duplication and divergence of genes encoding metabolic enzymes. Division of the functions of early generalist enzymes enhanced catalytic power and control over metabolic fluxes. Later, novel enzymes evolved from inefficient secondary activities in specialized enzymes. Enzymes operate in the context of complex metabolic and regulatory networks. The potential for evolution of a new enzyme depends upon the collection of enzymes in a microbe, the topology of the metabolic network, the environmental conditions, and the net effect of trade-offs between the original and novel activities of the enzyme. PMID- 22069331 TI - Carotenoid isomerase is key determinant of petal color of Calendula officinalis. AB - Orange petals of calendula (Calendula officinalis) accumulate red carotenoids with the cis-configuration at the C-5 or C-5' position (5-cis-carotenoids). We speculated that the orange-flowered calendula is a carotenoid isomerase (crtiso) loss-of-function mutant that impairs the cis-to-trans conversion of 5-cis carotenoids. We compared the sequences and enzyme activities of CRTISO from orange- and yellow-flowered calendulas. Four types of CRTISO were expressed in calendula petals. The deduced amino acid sequence of one of these genes (CoCRTISO1) was different between orange- and yellow-flowered calendulas, whereas the sequences of the other three CRTISOs were identical between these plants. Analysis of the enzymatic activities of the CoCRTISO homologs showed that CoCRTISO1-Y, which was expressed in yellow petals, converted carotenoids from the cis-to-trans-configuration, whereas both CoCRTISO1-ORa and 1-ORb, which were expressed in orange petals, showed no activity with any of the cis-carotenoids we tested. Moreover, the CoCRTISO1 genotypes of the F2 progeny obtained by crossing orange and yellow lines linked closely to petal color. These data indicate that CoCRTISO1 is a key regulator of the accumulation of 5-cis-carotenoids in calendula petals. Site-directed mutagenesis showed that the deletion of Cys-His His at positions 462-464 in CoCRTISO1-ORa and a Gly-to-Glu amino acid substitution at position 450 in CoCRTISO1-ORb abolished enzyme activity completely, indicating that these amino acid residues are important for the enzymatic activity of CRTISO. PMID- 22069333 TI - E1-E2 interactions in ubiquitin and Nedd8 ligation pathways. AB - Initial rates of E1-catalyzed E2 transthiolation have been used as a reporter function to probe the mechanism of 125I-ubiquitin transfer between activation and ligation half-reactions of ubiquitin conjugation. A functional survey of 11 representative human E2 paralogs reveals similar Km for binding to human Uba1 ternary complex (Km(ave)=121+/-72 nm) and kcat for ubiquitin transfer (kcat(ave)=4.0+/-1.2 s(-1)), suggesting that they possess a conserved binding site and transition state geometry and that they compete for charging through differences in intracellular concentration. Sequence analysis and mutagenesis localize this binding motif to three basic residues within Helix 1 of the E2 core domain, confirmed by transthiolation kinetics. Partial conservation of the motif among E2 paralogs not recognized by Uba1 suggests that another factor(s) account for the absolute specificity of cognate E2 binding. Truncation of the Uba1 carboxyl-terminal beta-grasp domain reduces cognate Ubc2b binding by 31-fold and kcat by 3.5*10(4)-fold, indicating contributions to E2 binding and transition state stabilization. Truncation of the paralogous domain from the Nedd8 activating enzyme has negligible effect on cognate Ubc12 transthiolation but abrogates E2 specificity toward non-cognate carrier proteins. Exchange of the beta-grasp domains between ubiquitin and Nedd8 activating enzymes fails to reverse the effect of truncation. Thus, the conserved Helix 1 binding motif and the beta-grasp domain direct general E2 binding, whereas the latter additionally serves as a specificity filter to exclude charging of non-cognate E2 paralogs in order to maintain the fidelity of downstream signaling. PMID- 22069332 TI - O-GlcNAcylation, novel post-translational modification linking myocardial metabolism and cardiomyocyte circadian clock. AB - The cardiomyocyte circadian clock directly regulates multiple myocardial functions in a time-of-day-dependent manner, including gene expression, metabolism, contractility, and ischemic tolerance. These same biological processes are also directly influenced by modification of proteins by monosaccharides of O-linked beta-N-acetylglucosamine (O-GlcNAc). Because the circadian clock and protein O-GlcNAcylation have common regulatory roles in the heart, we hypothesized that a relationship exists between the two. We report that total cardiac protein O-GlcNAc levels exhibit a diurnal variation in mouse hearts, peaking during the active/awake phase. Genetic ablation of the circadian clock specifically in cardiomyocytes in vivo abolishes diurnal variations in cardiac O-GlcNAc levels. These time-of-day-dependent variations appear to be mediated by clock-dependent regulation of O-GlcNAc transferase and O-GlcNAcase protein levels, glucose metabolism/uptake, and glutamine synthesis in an NAD independent manner. We also identify the clock component Bmal1 as an O-GlcNAc modified protein. Increasing protein O-GlcNAcylation (through pharmacological inhibition of O-GlcNAcase) results in diminished Per2 protein levels, time-of-day dependent induction of bmal1 gene expression, and phase advances in the suprachiasmatic nucleus clock. Collectively, these data suggest that the cardiomyocyte circadian clock increases protein O-GlcNAcylation in the heart during the active/awake phase through coordinated regulation of the hexosamine biosynthetic pathway and that protein O-GlcNAcylation in turn influences the timing of the circadian clock. PMID- 22069334 TI - Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP regulated deoxynucleotide triphosphohydrolase. AB - The SAMHD1 protein is an HIV-1 restriction factor that is targeted by the HIV-2 accessory protein Vpx in myeloid lineage cells. Mutations in the SAMHD1 gene cause Aicardi-Goutieres syndrome, a genetic disease that mimics congenital viral infection. To determine the physiological function of the SAMHD1 protein, the SAMHD1 gene was cloned, recombinant protein was produced, and the catalytic activity of the purified enzyme was identified. We show that SAMHD1 contains a dGTP-regulated deoxynucleotide triphosphohydrolase. We propose that Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication. PMID- 22069336 TI - Editorial. PMID- 22069335 TI - Role of forward translocation in nucleoside triphosphate phosphohydrolase I (NPH I)-mediated transcription termination of vaccinia virus early genes. AB - Termination of transcription of vaccinia virus early genes requires the virion form of the viral RNA polymerase (RNAP), a termination signal (UUUUUNU) in the nascent RNA, vaccinia termination factor, nucleoside triphosphate phosphohydrolase I (NPH I), and ATP. NPH I uses ATP hydrolysis to mediate transcript release, and in vitro, ATPase activity requires single-stranded DNA. NPH I shows sequence similarity with the DEXH-box family of proteins, which includes an Escherichia coli ATP-dependent motor protein, Mfd. Mfd releases transcripts and rescues arrested transcription complexes by moving the transcription elongation complex downstream on the DNA template in the absence of transcription elongation. This mechanism is known as forward translocation. In this study, we demonstrate that NPH I also uses forward translocation to catalyze transcript release from viral RNAP. Moreover, we show that NPH I-mediated release can occur at a stalled RNAP in the absence of vaccinia termination factor and U(5)NU when transcription elongation is prevented. PMID- 22069337 TI - Learning spinal manipulation: a comparison of two teaching models. AB - PURPOSE: The goal of the present study was to quantify the high-velocity, low amplitude spinal manipulation biomechanical parameters in two cohorts of students from different teaching institutions. The first cohort of students was taught chiropractic techniques in a patient-doctor positioning practice setting, while the second cohort of students was taught in a "complete practice" manipulation setting, thus performing spinal manipulation skills on fellow student colleagues. It was hypothesized that the students exposed to complete practice would perform the standardized spinal manipulation with better biomechanical parameters. METHODS: Participants (n = 88) were students enrolled in two distinct chiropractic programs. Thoracic spine manipulation skills were assessed using an instrumented manikin, which allowed the measurement of applied force. Dependent variables included peak force, time to peak force, rate of force production, peak force variability, and global coordination. RESULTS: The results revealed that students exposed to complete practice demonstrated lower time to peak force values, higher peak force, and a steeper rate of force production compared with students in the patient-doctor positioning scenario. A significant group by gender interaction was also noted for the time to peak force and rate of force production variables. CONCLUSION: The results of the present study confirm the importance of chiropractic technique curriculum and perhaps gender in spinal manipulation skill learning. It also stresses the importance of integrating spinal manipulation skills practice early in training to maximize the number and the quality of significant learner-instructor interactions. PMID- 22069338 TI - Are patients receiving health promotion advice in the chiropractic teaching clinic setting?: an impact assessment of a brief intervention to increase advising rates and goal setting. AB - PURPOSE: The aim of this study was to analyze patient-reported health issues and levels of engagement, discussion of needed lifestyle changes, and goal setting with the patient's intern or staff doctor before and after a brief intervention to increase health-promoting activities in the clinic. METHODS: Patient surveys were developed and administered to outpatients before and after a brief intervention aimed at increasing staff and intern engagement with patients on health promotion measures. Patients self-reported areas of need and levels of engagement by their doctor or intern. Data were analyzed as pre- and postintervention independent, cross-sectional samples. Frequencies and chi-square assessments were performed. RESULTS: One hundred twenty-eight preintervention surveys and 162 postintervention surveys were collected. Back pain was the most common reason for being seen in the clinic (60% of patients) and most patients were white. More than 10% were smokers in both samples. Many patients reported poor diet, unhealthy weight, sleep issues, stress, or lack of regular physical activity, but 65% of the preintervention group and 72% of the postintervention group said a needed lifestyle change was discussed. Goals were set for 74% of the preintervention group and 84% of the postintervention group (p = .04). Information on lifestyle change was received by 52% of preintervention patients and 62% of postintervention patients and most were satisfied with this information. Goal setting was more common when a lifestyle change was discussed. Written information that was related to physical activity, for example, increased 350% (p < .0001). CONCLUSION: There are many opportunities for discussing needed lifestyle changes with patients. Patients self-report health behavioral issues related to physical activity, unhealthy weight, diet, stress, and sleep. More can be done in this area by this clinic, but initial assessments of impact from a brief intervention seem to have increased some levels of engagement by interns. PMID- 22069339 TI - Depressive symptoms in chiropractic students: a 3-year study. AB - BACKGROUND: The intensive training associated with health care education has been suggested to have unintended negative consequences on students' mental or emotional health that may interfere with the development of qualities deemed essential for proficient health care professionals. This longitudinal study examined the prevalence and severity of depressive symptoms among students at a chiropractic educational institution. METHODS: Chiropractic students at all levels of training were surveyed at Canadian Memorial Chiropractic College during the academic years of 2000/2001, 2001/2002, and 2002/2003. The measurement tool employed was the Beck Depression Inventory, 2nd edition (BDI-II). Previously established BDI-II cutoff scores were used to assess the severity of reported depression symptoms, and these were compared by sex and year of training. RESULTS: The survey was completed by 1303 students (70%) over the 3 years of the study. The prevalence of depressive symptoms was nearly 25%, with 13.7% of respondents indicating a rating of mild depression, 7.1% indicating moderate depressive symptoms, and 2.8% indicating severe symptoms. Significant differences were found between years of training, with 2nd-year students having the highest prevalence of depressive symptoms, and sex, with females having a higher rate of symptoms. CONCLUSIONS: Chiropractic students surveyed at Canadian Memorial Chiropractic College had high rates of depression similar to those measured in other health care profession students. Chiropractic educational institutions should be aware of this situation and are encouraged to emphasize students' awareness of their own personal health and well-being and their access to appropriate care, in addition to the same concerns for their future patients. PMID- 22069341 TI - Faculty perception of clinical value of five commonly used orthopedic tests. AB - PURPOSE: The purpose of this study is to examine the perceptions of the value of five orthopedic tests (straight leg raise, Braggard's test, Kemp's test, Valsalva maneuver, and Patrick's fabere test) in the diagnosis of specific neuromusculoskeletal conditions among the chiropractic faculty at a large chiropractic college. METHODS: This is an observational study that employed a survey of 41 academic and clinic faculty members with a Doctor of Chiropractic degree. RESULTS: Of the 12 posed questions, only five demonstrated statistically significant consistency (positive straight leg raise for the presence of disc pathology, positive Valsalva maneuver for the presence of disc pathology, negative Valsalva maneuver to rule out disc pathology, negative Braggard's test to rule out the presence of disc pathology, and positive Patrick's fabere test for the presence of hip joint pathology). Subgroup analysis demonstrated that the school of graduation may be the only predictor of consistency. CONCLUSION: There were strong indications that faculty members were not consistent in their perception of the value for common orthopedic tests for diagnosing specific conditions. In an evidence-based model of education, there should be a consensus among academic and clinical faculty in order for the students to learn, integrate, and apply in practice what they have learned in the classroom. Active intervention in the academic process is required to accomplish necessary change. PMID- 22069340 TI - Perception of educational environment among undergraduate students in a chiropractic training institution. AB - PURPOSE: The impact of the educational environment in student learning is well documented. However, there is a scarcity in the literature exploring the educational environment in chiropractic training institutions. This study aimed to identify the perceived educational environment in a chiropractic training institution and the possible perceptual differences among different demographic groups. METHODS: The perceived educational environment was surveyed using Dundee Ready Education Environment (DREEM), which is a validated, self-administered, and Likert-type inventory. DREEM items focus on subdomains related to learning, teachers, self-confidence, academic atmosphere, and social environment. The results were analyzed and interpreted in relation to standard norms of DREEM and demographic variables. RESULTS: The survey was completed by 124 chiropractic undergraduate students (response rate 83%). Statistically, the inventory items showed high correlation and the subdomains showed a close relationship. Overall the DREEM score was very high: 156.1/200 (78%). The subdomain scores were also at very high levels. However, the scoring of four items by students was consistently poor: lack of a support system for stressed students, 1.8 (SD 1.1); authoritarian teachers, 1.8 (SD 1.2); inadequate school time-tabling, 2.0 (SD 1.1); and overemphasis on factual learning, 2.0 (SD 1.0). There were no statistically significant differences in DREEM scores between gender, age, minority, and ethnicity groups. CONCLUSIONS: In general, students perceived that a sound educational environment is fostered by the institution and its educational program for all students despite their demographic variations. However, certain specific elements of the educational process may need to be addressed to improve the educational experience. PMID- 22069342 TI - A history of the journal of chiropractic education: twenty-five years of service, 1987-2011. AB - PURPOSE: The Journal of Chiropractic Education celebrates its 25th anniversary in the year 2011. The purpose of this article is to chronicle the history of the journal, which is unreported at this time. METHODS: The entire collection of the journal was reviewed and information pertaining to important events and changes in the format, personnel, and processes of the journal were extracted. This information was used to create a chronology of the journal. The chronology was complemented with information obtained from people who were involved in the evolution of the journal and the Association of Chiropractic Colleges Educational Conferences. RESULTS: Starting as a humble newsletter in 1987 and produced for a small cadre of readers primarily from the United States, the journal is now a full-sized and bound peer-reviewed international journal. Initially cataloged by the Index to Chiropractic Literature and MANTIS, the indexing expanded to interdisciplinary indexing systems such as CINAHL and ultimately PubMed. The journal has grown to serve the needs of chiropractic educators from around the world with representatives on the editorial board from 39 colleges and universities from 15 different countries. The journal has grown in tandem with the profession's leading education and research conference and has been the primary repository for the scholarship of chiropractic education. CONCLUSION: The history of the journal represents a significant milestone in the development of the chiropractic profession, particularly the discipline of chiropractic education. The journal has had an interesting history and the future promises to bring more opportunities and challenges to the field of chiropractic education and to the journal. PMID- 22069343 TI - Allowing a possible margin of error when assessing student skills in spinous process location. AB - INTRODUCTION: Spinal palpation is subject to inconsistency between examiners. When testing students on the location of vertebral spinous processes, faculty examiners may wish to allow for a margin of error that is observed between experienced practitioners. This study attempts to determine such a margin of error for selected vertebral levels that could be allowed in testing situations at Sherman Chiropractic College. This could serve as a model for other chiropractic colleges in determining their margins of error. METHODS: Two faculty clinicians palpated spinous processes at four different vertebral levels (C2, T3, T9, and L2) on 18 student volunteers. Differences for each vertebral level, along with one, two, and three standard deviations, were calculated. RESULTS: AVERAGE DIFFERENCES BETWEEN EXAMINERS INCREASED CAUDALLY, AS FOLLOWS: C2, 4.23 +/- 3.77 mm; T3, 13.41 +/- 10.53 mm; T9, 18.17 +/- 17.62 mm; L2, 18.70 +/- 16.58 mm. DISCUSSION: In this study, faculty examiners exhibited variation in their locations of spinous processes for these vertebrae. These variations could be allowed when assessing student skills in locating these spinous processes at this chiropractic college. CONCLUSION: In this study, differences between examiners plus or minus one standard deviation ranged from 4.23 +/- 3.77 mm for C2 to 18.70 +/- 16.58 mm for L2. The concept of margin of error should be considered by faculty examiners when assessing the skill of students in locating the spinous process of various vertebral levels. PMID- 22069344 TI - 2011 association of chiropractic colleges educational conference and research agenda conference. PMID- 22069345 TI - Letters to the editor. PMID- 22069346 TI - Evaluation of contrast visual acuity in patients with retinitis pigmentosa. AB - BACKGROUND: The purpose of this study was to determine visual acuity at different contrast levels under photopic and mesopic conditions in patients with retinitis pigmentosa. METHODS: Sixty eyes of 31 normal controls, 92 eyes of 52 patients with retinitis pigmentosa without other ocular disorders (RP-1 group), and 20 eyes of 14 patients with retinitis pigmentosa with cataracts and without other ocular disorders (RP-2 group) were studied. Conventional visual acuity was measured using a conventional Landolt ring chart with 100% contrast and luminance of 150 cd/m(2). All of the patients with retinitis pigmentosa had a decimal visual acuity better than 1.0. Contrast visual acuity was measured with the same Landolt ring chart with contrasts of 100% and 10% and under photopic (200 cd/m(2)) and mesopic (10 cd/m(2)) conditions. Decimal visual acuities were converted to logMAR units for the analyses. RESULTS: The 100% contrast visual acuity and the 10% contrast visual acuity determined under both photopic and mesopic conditions were significantly poorer in both the RP-1 and RP-2 groups than in the controls. The differences between the conventional visual acuity and the 100% contrast visual acuity were significantly greater in the RP-1 and RP-2 groups than in the controls under both photopic and mesopic conditions. The differences between the 100% contrast visual acuity and the 10% contrast visual acuity were not significant among the three groups under photopic and mesopic conditions. CONCLUSION: Contrast visual acuities were greatly reduced in patients with retinitis pigmentosa with relatively well preserved conventional visual acuity, and the contrast visual acuity was largely influenced by ambient light levels in patients with retinitis pigmentosa. Although a longitudinal study for confirmation has to be performed, our findings indicate that contrast visual acuity is a better test to follow changes in visual function in patients with retinitis pigmentosa. PMID- 22069347 TI - Persistent subretinal fluid due to central serous chorioretinopathy after retinal detachment surgery. AB - BACKGROUND: The causes of persistent submacular detachment after successful rhegmatogenous retinal detachment (RRD) surgery remain unknown. Its presence is associated with poor postoperative visual acuity, but due to its spontaneous resolution no additional therapeutic or diagnostic procedure is recommended. CASE REPORT: A case of central serous chorioretinopathy (CSC) that simulated persistent subfoveal fluid after RRD surgery is presented. CONCLUSION: To the authors' knowledge, no other case of visual impairment after successful retinal detachment surgery due to CSC has been reported in the PubMed database. In view of this report, CSC should be considered in the differential diagnosis of persistent subretinal fluid after successful retinal detachment surgery. PMID- 22069348 TI - Comparison of selective laser trabeculoplasty (SLT) in primary open angle glaucoma and pseudoexfoliation glaucoma. AB - BACKGROUND AND OBJECTIVE: The aim of the present study was to compare intraocular pressure (IOP) reduction and inflammation after selective laser trabeculoplasty (SLT) treatment in patients suffering from primary open angle (POAG) vs pseudoexfoliative (PXFG) glaucoma. STUDY DESIGN/PATIENTS AND METHODS: Sixty patients (60 eyes) participated in the study. Glaucoma patients (POAG or PXFG) scheduled for treatment with SLT were included. Inflammation was measured with a laser flare meter (Kowa FM-500). Measurements were made before SLT and 2 hours, 1 week, and 1 month after SLT treatment. IOP was also checked at the same time intervals. RESULTS: Inflammation after SLT showed no significant difference between the groups (t-test, before: P = 0.16; 2 hours: P = 0.14; 1 week: P = 0.12; and 1 month: P = 0.36). IOP reduction was the same in both groups (t-test, P = 0.27). CONCLUSION: SLT safely reduces IOP in both POAG and PXFG. Pseudoexfoliation does not seem to be a risk factor for post-laser complications. PMID- 22069349 TI - The use of bevacizumab in a multilevel retinal hemorrhage secondary to retinal macroaneurysm: a 39-month follow-up case report. AB - PURPOSE: The evaluation of long-term visual outcome after the use of bevacizumab for the management of multilevel hemorrhage due to retinal arterial macroaneurysm (MA). CASE REPORT: A 71-year-old hypertensive female presented with sudden reduction of visual acuity in her left eye (OS). Fundoscopy revealed an arterial macroaneurysm with preretinal and subretinal hemorrhage in the eye. Due to significant macular involvement, the patient received two intravitreal injections of bevacizumab within 2 months. RESULTS: Significant visual and anatomical recovery was observed 2 months later, which was confirmed by fluorescein angiography. At the end of a follow-up period (39 months) visual acuity and visual field were at normal levels. CONCLUSION: Retinal MA is a relatively rare condition. Anti-vascular endothelial growth factor therapy appears a safe and effective treatment option for selected symptomatic individuals that may offer faster visual rehabilitation. Herein we report, for the first time, a 39-month follow-up of a retinal MA treated with anti-vascular endothelial growth factor therapy. PMID- 22069350 TI - Ocular onchocerciasis: current management and future prospects. AB - This paper reviews the current management of onchocerciasis and its future prospects. Onchocerciasis is a disease affecting millions of people in Africa, South and Central America, and Yemen. It is spread by the blackfly as a vector and caused by the filarial nematode, Onchocerca volvulus. A serious attempt was made by the Onchocerciasis Control Program between 1975 and 2002 to eliminate the vector in eleven of the endemic countries in West Africa, and with remarkable success. Formerly, the treatment was with diethyl carbamazine for the microfilaria and suramin for the adult worm. These drugs are now known to be toxic and unsuitable for mass distribution. In particular, they precipitate optic nerve disease. With the discovery of ivermectin, a much safer microfilaricide, and the decision of Merck to distribute the drug free of charge for as long as needed, the strategy of control switched to mass drug administration through community-directed treatment with ivermectin. So far, millions have received this annual or biannual treatment through the African Program for Onchocerciasis Control and the Onchocerciasis Elimination Program for the Americas. However, the problem with ivermectin is that it is a monotherapy microfilaricide which has limited effect on the adult worm, and thus will need to be continued for the life span of the adult worm, which may last up to 15 years. There are also early reports of resistance. Serious encephalopathy and death may occur when ivermectin is used in subjects heavily infested with loiasis. It seems unlikely that a break in transmission will occur with community-directed treatment with ivermectin in Africa because of population migrations and the highly efficient vector, but in the Americas some countries such as Columbia and the Oaxaca focus in Mexico have reported eradication. Vector control is only now applicable in selected situations, and particularly to control the nuisance value of the blackfly. Trials are ongoing for alternatives to ivermectin. Candidate drugs include moxidectin, a macrofilaricide, doxycycline which targets the Wolbachia endosymbiont, and flubendazole, which shows promise with the newer oral cyclodextrin formulation. PMID- 22069351 TI - Translational research in retinology. AB - Clinical laboratories are strong, integral partners in personalized health care. Laboratory databases hold a vast amount of data on human phenotypes, genotypes, biomarkers, progression of disease, and response to therapy. These structured and unstructured free text data are critical for patient care and a resource for personalized medicine and translational research. Laboratory data are integrated into many electronic medical records that provide "summary reports" and "trending" to visualize longitudinal patient data. Recent advances in ophthalmology such as gene therapy, cell therapy using stem cells, and also retinal prosthesis explore the potential of translational research marking a new era in research into the diagnosis and treatment of eye diseases. PMID- 22069352 TI - Evaluation of patients' experiences at different stages of the intravitreal injection procedure - what can be improved? AB - INTRODUCTION: Intravitreal injection of ranibizumab has become one of the most commonly performed ophthalmic procedures. It is timely to conduct an evaluation of the injection procedure from the patient's perspective so as to determine ways to improve patient experience. The purpose of this study was to quantitatively describe patients' experiences of the different stages of the intravitreal injection procedure and provide suggestions for improvement. METHOD: Following intravitreal injection, patients were administered a questionnaire to score the distress felt for each of ten parts of the whole injection process from the initial waiting to the final instillation of topical antibiotic at the end. A score of higher than 4 was regarded as significantly unpleasant. The proportion of scores above 4 for each step was used to evaluate the relative distress experienced by patients for the different parts of the procedure. RESULTS: A total of 42 patients were surveyed. The step with the highest percentage of patients scoring more than 4 was the injection step (19%). However, cumulatively, the steps relating to the application of the drape, the speculum, and the removal of drape accounted for 53% of scores greater than 4. CONCLUSION: There is considerable variation in how patients tolerate different stages of the injection procedure. The needle entry was the most unpleasant step followed by the draping steps cumulatively. Use of subconjunctival anesthesia, a perforated drape, and alternative lid exclusion devices may help to improve the patient's tolerability of the procedure and experience. PMID- 22069353 TI - Donor and surgical risk factors for primary graft failure following Descemet's stripping automated endothelial keratoplasty in Asian eyes. AB - BACKGROUND: Descemet's stripping automated endothelial keratoplasty (DSAEK) has been shown to have superior refractive and visual results compared with penetrating keratoplasty, but higher rates of primary graft failure (PGF). This paper presents donor and surgical risk factors for PGF in DSAEK cases in Asian eyes. DESIGN: Retrospective case-control study. PARTICIPANTS: All consecutive patients who underwent DSAEK at a tertiary referral teaching hospital from March 2006-December 2008. METHODS: DONOR DETAILS ANALYZED WERE: age of donor, cause of donor death, death to harvesting time, donor storage time, distribution distance of tissue, preoperative endothelial cell count. Surgical factors analyzed were: donor diameter, donor thickness, and method of donor insertion. These risk factors in cases of PGF were compared with patients with successful DSAEK as the control group. MAIN OUTCOME MEASURE: PGF. RESULTS: A total of 124 DSAEK procedures were performed. Six DSAEK procedures (five eyes of five patients; one eye with two failures) resulted in PGF (4.8%). Significant risk factors were found for PGF to include graft insertion using a folding technique (odds ratio [OR], 34.03; 95% confidence interval [CI], 3.75-314.32; P = 0.0017) and a small donor diameter (OR, 39.94; 95% CI, 2.18-732.17; P = 0.013). CONCLUSION: The results of this study suggest that in Asian eyes with shallow anterior chambers, surgical trauma relating to the technique of donor insertion, and the use of a small donor are major risk factors for PGF following DSAEK. PMID- 22069354 TI - Hemiretinal vein occlusion with macular hemorrhage and edema treated with intravitreal bevacizumab. AB - A 39-year-old male with decreased visual acuity and extensive macular hemorrhage and edema secondary to a hemiretinal vein occlusion was treated with multiple intravitreal injections of bevacizumab 1.25 mg every four to six weeks for over one year. Treatment outcomes were assessed by visual acuity and Cirrus spectral domain optical coherence tomography. Treatment resulted in ongoing visual and anatomic improvement, with resolution at the last visit. PMID- 22069355 TI - Additive intraocular pressure-lowering effect of dorzolamide 1%/timolol 0.5% fixed combination on prostaglandin monotherapy in patients with normal tension glaucoma. AB - PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of adding dorzolamide 1.0%/timolol 0.5% fixed combination (DTFC) to prostaglandin analogs (PGAs) as monotherapy in patients with normal tension glaucoma. METHODS: A prospective, clinical, case-controlled study of patients with normal tension glaucoma. Patients had been on a once-daily night dose of prostaglandins (PGs) as monotherapy and then received DTFC added to PGs for 8 weeks. The IOP was measured at 9 am, week 0 (baseline), week 4, and week 8. RESULTS: The baseline IOP of 40 patients who had previously been treated by prostaglandin monotherapy was 15.6 +/ 2.0 mmHg at baseline. The IOPs at 4 and 8 weeks after adding DTFC to PGs were 13.5 +/- 2.1 mmHg and 13.7 +/- 2.2 mmHg, respectively. Significant decrease of the IOP was observed at each time point of measurement as compared with the baseline IOP before adding DTFC (P = 0.01). The percent IOP reduction from the baseline IOP at week 4 and week 8 was 13.5% +/- 12.3% and 11.7% +/- 13.1%, respectively. The percentage of patients who achieved 10% or more IOP reduction from the baseline IOP at week 8 was 62.5%. The baseline IOP was significantly correlated with the percent IOP reduction at week 8 (P = 0.03, r = 0.34). CONCLUSION: DTFC therapy added to PGAs as glaucoma monotherapy is effective in patients with normal tension glaucoma. PMID- 22069356 TI - Evaluation of retrobulbar blood flow in patients with age-related cataract; color Doppler ultrasonographic findings. AB - OBJECTIVES: Cataracts are the most common cause of blindness worldwide, with cataract surgery being the most common ophthalmic procedure. To our best knowledge, this is the first case-control study with a large number of participants to evaluate ocular blood flow in patients with cataracts. MATERIALS AND METHODS: Color Doppler and duplex sonography of the orbital vessels was performed in 224 eyes of 112 patients with known bilateral age-related cataracts and in 76 eyes of 38 healthy age- and sex-matched volunteers. RESULTS: The mean +/- (standard deviation [SD]) of peak systolic velocity (PSV) of the ophthalmic artery in patients with cataracts (34.59 +/- 22.49 cm/second) was significantly different to that in controls (52.11 +/- 14.01 cm/second) (P < 0.001). The mean +/- SD PSV of the central retinal artery in patients with cataracts (15.31 +/- 4.93 cm/second) was significantly different to that in controls (9.61 +/- 5.64 cm/second) (P < 0.001). CONCLUSION: The mean PSV and resistive index (RI) of the ophthalmic and central retinal arteries were lower in cataract patients when compared with normal subjects. This suggests that ocular hypoperfusion and changes in ocular hemodynamic may have a role in the formation of age-related cataracts. PMID- 22069357 TI - Improving near vision in presbyopic eyes by selective treatment of high-order aberrations. AB - PURPOSE: Evaluation of improving near vision in presbyopic patients with low to moderate myopia with selective treatment of high-order aberrations (HOAs) using the ORK-CAM software aberrometer and a SCHWIND ESIRIS excimer laser. In this study, all HOAs except vertical coma were treated and the effect on near visual function was evaluated. SETTING: Horus Vision Correction Center, Alexandria, Egypt. METHODS: Twenty-six presbyopic patients (52 eyes) with low to moderate myopia were divided into two groups, A and B. The ORK-CAM software aberrometer was used in both groups to measure HOAs and design wavefront-guided treatment. All included eyes had total coma >0.2 MUm. The Moria M2 mechanical microkeratome was used for flap making in both groups. Wavefront-guided laser-assisted in situ keratomileusis using ESIRIS laser was done for all eyes. In Group A (30 eyes) all HOAs were treated. In Group B (22 eyes) vertical coma was left untreated. Postoperative uncorrected distance visual acuity (UCVA), best corrected distance visual acuity (BCVA), uncorrected near acuity (UCNA), distance corrected near acuity (DCNA), best corrected near acuity with addition for near vision (BCNA), manifest refractive spherical equivalent (MRSE), HOAs, and contrast sensitivity for both groups were done preoperatively and at 3 months postoperatively. RESULTS: Mean age was 47.46 and 45.2 years for groups A and B, respectively. Mean preoperative MRSE was -2.37 and -2.87 D and mean preoperative total HOAs was 0.35 and 0.38 MUm in groups A and B, respectively. There was no significant difference between groups regarding age, sex, preoperative MRSE, and preoperative total HOAs. After 3 months, there was no significant difference between groups in terms of UCVA, BCVA, MRSE, and contrast sensitivity. Analysis of postoperative HOAs showed significant difference in vertical coma between the two groups (P < 0.001). DCNA was significantly better in Group B (P < 0.01). CONCLUSION: Treating low to moderate myopia with wavefront-guided ablation including selective treatment of HOAs might be very useful for improving visual functions. Treating all HOAs but the vertical coma improved uncorrected near acuity in presbyopic patients. PMID- 22069358 TI - Risk factors for primary open-angle glaucoma in Japanese subjects attending community health screenings. AB - BACKGROUND/AIMS: To describe risk factors associated with primary open-angle glaucoma (POAG) in Japanese subjects who participated in community health screenings. METHODS: Residents of Akita, Japan, participating in a community health checkup were selected to undergo a comprehensive ophthalmic examination. Glaucoma was diagnosed based on optic disk appearance, perimetric results, and other ocular findings. Systemic blood pressure and intraocular pressure were measured and ocular perfusion pressure was calculated. Logistic regression analysis was performed to determine risk factors for POAG patients. RESULTS AND CONCLUSION: Of the 710 subjects examined, 26 had POAG. The estimated prevalence of POAG was 3.7%. After adjusting for age, the prevalence of POAG was similar to that found in the Tajimi Study of Japanese subjects. Multivariate logistic regression analysis demonstrated that older age (>=60 years, odds ratio [OR]: 3.49), lower diastolic blood pressure (<=58 mmHg, OR: 2.11), higher intraocular pressure (>=19 mmHg, OR: 4.12), and lower ocular perfusion pressure (<=34 mmHg, OR: 5.78) were associated with increased risk of having POAG. These findings may be relevant for identifying high risk groups. PMID- 22069359 TI - Massive vitreous gel incarceration into the subretinal space following traumatic retinal detachment in a young patient: a case report. AB - PURPOSE: This paper reports a young patient with a traumatic rhegmatogenous retinal detachment and massive vitreous gel incarceration into the subretinal space, who was successfully treated with 23-gauge transconjunctival vitrectomy. CASE REPORT: An 11-year-old boy was referred to the authors' clinic with traumatic retinal detachment in the right eye, 2 weeks after ocular contusion in a baseball accident. At the time of the injury, emergency fundus examination by his local doctor had revealed vitreous hemorrhage in the inferior quadrant of the right eye. Visual acuity was 1.5. He had continued to play baseball as usual for 2 weeks after the injury. At his first visit to the authors' clinic, fundus examination showed a highly bullous retinal detachment involving the inferior two quadrants, associated with multiple irregular retinal breaks. There was an oval hole in the inferior quadrant which was 10-disc diameter * 5-disc diameter in size and was surrounded by edematous and hemorrhagic retina. The macula remained attached. Absolute rest for 4 hours in the supine position with binocular occlusion did not diminish the height of the retinal detachment. A 23-gauge three port pars plana vitrectomy combined with 360 degrees circumferential buckling was performed under general anesthesia. The lens was retained. Incarceration of massive vitreous gel, including vitreous hemorrhage into the subretinal space through the largest break, was observed during vitrectomy. Reattachment of the retina was achieved by fluid-air exchange and internal tamponade using SF(6) gas. At follow-up at 9 months, the retina remained attached and visual acuity in the right eye was 1.2. PMID- 22069360 TI - Determinants of polypharmacy and compliance with GOLD guidelines in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Polypharmacy of respiratory medications is commonly observed in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to investigate determinants of polypharmacy and to study the consistency of actual respiratory drug use with current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in pulmonary rehabilitation candidates with COPD. METHODS: Data were extracted from the records of all patients with a diagnosis of COPD referred for pulmonary rehabilitation to CIRO+ between 2005 and 2009. Use of respiratory medications, self-reported COPD exacerbations, lung function, blood gases, exercise capacity, Medical Research Council (MRC) dyspnea grade, and St George's Respiratory Questionnaire (SGRQ) were recorded as part of assessment of health status. RESULTS: In total, 1859 COPD patients of mean age (+/- standard deviation) 64.3 +/- 9.7 years and with a forced expiratory volume in one second (FEV(1)) of 44.7% +/- 18.2% were included. On average, patients used 3.5 +/- 1.5 respiratory medications; this number increased with increasing GOLD stage, MRC score, and SGRQ scores. FEV(1) (% predicted), SGRQ, and number of recent exacerbations were independent determinants of polypharmacy. Use of long-acting bronchodilators and inhaled corticosteroids was substantial and comparable in all GOLD stages. Use of corticosteroids was not restricted to patients with frequent exacerbations. CONCLUSION: Polypharmacy of respiratory medications is common in COPD patients with persistent symptoms. In addition to severity of disease, health status is an independent predictor of polypharmacy. Actual drug use in COPD patients referred for pulmonary rehabilitation is partially inconsistent with current GOLD guidelines. PMID- 22069361 TI - Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation. OBJECTIVES: The present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control. METHODS: COPD patients with forced expiratory volume in one second <65% and plethysmographic functional residual capacity >=120% of predicted were randomized to a double-blind, double-dummy, 12-week, parallel group, treatment with either BDP/F 400/24 MUg/day or FP/S 500/100 MUg/day. Lung volumes were measured with full body plethysmography, and dyspnea was measured with transition dyspnea index. RESULTS: Eighteen patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F versus FP/S. CONCLUSION: BDP/F extra-fine combination is effective in reducing air trapping and dyspnea in COPD patients with lung hyperinflation. PMID- 22069362 TI - Factors associated with good self-rated health and quality of life in subjects with self-reported COPD. AB - BACKGROUND: Recent guidelines for chronic obstructive pulmonary disease (COPD) state that COPD is both preventable and treatable. To gain a more positive outlook on the disease it is interesting to investigate factors associated with good, self-rated health and quality of life in subjects with self-reported COPD in the population. METHODS: In a cross-sectional study design, postal survey questionnaires were sent to a stratified, random population in Sweden in 2004 and 2008. The prevalence of subjects (40-84 years) who reported having COPD was 2.1% in 2004 and 2.7% in 2008. Data were analyzed for 1475 subjects. Regression models were used to analyze the associations between health measures (general health status, the General Health Questionnaire, the EuroQol five-dimension questionnaire) and influencing factors. RESULTS: The most important factor associated with good, self-rated health and quality of life was level of physical activity. Odds ratios for general health varied from 2.4 to 7.7 depending on degree of physical activity, where subjects with the highest physical activity level reported the best health and also highest quality of life. Social support and absence of economic problems almost doubled the odds ratios for better health and quality of life. CONCLUSIONS: In this population-based public health survey, better self-rated health status and quality of life in subjects with self reported COPD was associated with higher levels of physical activity, social support, and absence of economic problems. The findings indicated that of possible factors that could be influenced, promoting physical activity and strengthening social support are important in maintaining or improving the health and quality of life in subjects with COPD. Severity of the disease as a possible confounding effect should be investigated in future population studies. PMID- 22069363 TI - Predictive properties of different multidimensional staging systems in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is considered to be a respiratory disease with systemic manifestations. Some multidimensional staging systems, not based solely on the level of airflow limitation, have been developed; however, these systems have rarely been compared. METHODS: We previously recruited 150 male outpatients with COPD for an analysis of factors related to mortality. For this report, we examined the discriminative and prognostic predictive properties of three COPD multidimensional measurements. These indices were the modified BODE (mBODE), which includes body mass index, airflow obstruction, dyspnea, and exercise capacity; the ADO, composed of age, dyspnea, and airflow obstruction; and the modified DOSE (mDOSE), comprising dyspnea, airflow obstruction, smoking status, and exacerbation frequency. RESULTS: Among these indices, the frequency distribution of the mBODE index was the most widely and normally distributed. Univariate Cox proportional hazards analyses revealed that the scores on three indices were significantly predictive of 5-year mortality of COPD (P < 0.001). The scores on the mBODE and ADO indices were more significantly predictive of mortality than forced expiratory volume in 1 second, the Medical Research Council dyspnea score, and the St. George's Respiratory Questionnaire total score. However, peak oxygen uptake on progressive cycle ergometry was more significantly related to mortality than the scores on the three indices (P < 0.0001). CONCLUSION: The multidimensional staging systems using the mBODE, ADO, and mDOSE indices were significant predictors of mortality in COPD patients, although exercise capacity had a more significant relationship with mortality than those indices. The mBODE index was superior to the others for its discriminative property. Further discussion of the definition of disease severity is necessary to promote concrete multidimensional staging systems as a new disease severity index in guidelines for the management of COPD. PMID- 22069364 TI - Spirometry for patients in hospital and one month after admission with an acute exacerbation of COPD. AB - AIM: To assess whether spirometry done in hospital during an admission for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is clinically useful for long-term management. METHODS: Patients admitted to hospital with a clinical diagnosis of AECOPD had spirometry post-bronchodilator at discharge and approximately 4 weeks later. RESULTS: Spirometry was achieved in less than half of those considered to have AECOPD. Of 49 patients who had spirometry on both occasions, 41 met the GOLD criteria for COPD at discharge and 39 of these met the criteria at 1 month. For the 41, spirometry was not statistically different between discharge and 1 month but often crossed arbitrary boundaries for classification of severity based on FEV(1). The eight who did not meet GOLD criteria at discharge were either misclassified due to comorbidities that reduce FVC, or they did not have COPD as a cause of their hospital admission. CONCLUSION: Spirometry done in hospital at the time of AECOP is useful in patients with a high pre-test probability of moderate-to-severe COPD. Small changes in spirometry at 1 month could place them up or down one grade of severity. Spirometry at discharge may be useful to detect those who warrant further investigation. PMID- 22069365 TI - Cost trends among commercially insured and Medicare Advantage-insured patients with chronic obstructive pulmonary disease: 2006 through 2009. AB - BACKGROUND: Few estimates of health care costs related to chronic obstructive pulmonary disease (COPD) are available regarding commercially insured patients in the United States. The aims of this retrospective observational analysis of administrative data were to describe and compare health care resource use and costs related to COPD in the United States for patients with commercial insurance or Medicare Advantage with Part D benefits, and to assess cost trends over time. METHODS: Patient-level and visit-level health care costs in the calendar years 2006, 2007, 2008, and 2009 were assessed for patients with evidence of COPD. Generalized linear models adjusting for sex, age category, and geographic region were used to investigate cost trends over time for patients with Medicare or commercial insurance. RESULTS: Medical costs, which ranged from an annual mean of US$2382 (Medicare 2007) to US$3339 (commercial 2009) per patient, comprised the majority of total costs in all years for patients with either type of insurance. COPD-related costs were less for Medicare than commercial cohorts. In the multivariate analysis, total costs increased by approximately 6% per year for commercial insurance patients (cost ratio 1.06; 95% confidence interval [CI] 1.04 1.07; P < 0.001) and 5% per year for Medicare patients (cost ratio 1.05; 95% CI 1.03-1.07; P < 0.001). Costs for outpatient and emergency department visits increased significantly over time in both populations. Standard admission costs increased significantly for Medicare patients (cost ratio 1.03; 95% CI 1.00-1.05; P = 0.03), but not commercial patients, and costs for intensive care unit visits remained stable for both populations. CONCLUSION: COPD imposed a substantial economic burden on patients and the health care system, with costs increasing significantly in both the Medicare and commercial populations. PMID- 22069366 TI - Chronic airflow limitation in a rural Indian population: etiology and relationship to body mass index. AB - PURPOSE: Respiratory conditions remain a source of morbidity globally. As such, this study aimed to explore factors associated with the development of airflow obstruction (AFO) in a rural Indian setting and, using spirometry, study whether underweight is linked to AFO. METHODS: Patients > 35 years old attending a rural clinic in West Bengal, India, took a structured questionnaire, had their body mass index (BMI) measured, and had spirometry performed by an ancillary health care worker. RESULTS: In total, 416 patients completed the study; spirometry was acceptable for analysis of forced expiratory volume in 1 second in 286 cases (69%); 16% were noted to exhibit AFO. Factors associated with AFO were: increasing age (95% confidence interval (CI) 0.004-0.011; P = 0.005), smoking history (95% CI 0.07-0.174; P = 0.006), male gender (95% CI 0.19-0.47; P = 0.012), reduced BMI (95% CI 0.19-0.65; P = 0.02), and occupation (95% CI 0.12 0.84; P = 0.08). The mean BMI in males who currently smoked (n = 60; 19.29 kg/m(2); standard deviation [SD] 3.46) was significantly lower than in male never smokers (n = 33; 21.15 kg/m(2) SD 3.38; P < 0.001). AFO was observed in 27% of subjects with a BMI <18.5 kg/m(2), falling to 13% with a BMI >=18.5 kg/m(2) (P = 0.013). AFO was observed in 11% of housewives, 22% of farm laborers, and 31% of cotton/jute workers (P = 0.035). CONCLUSION: In a rural Indian setting, AFO was related to advancing age, current or previous smoking, male gender, reduced BMI, and occupation. The data also suggest that being under-weight is linked with AFO and that a mechanistic relationship exists between low body weight, smoking tobacco, and development of AFO. PMID- 22069367 TI - Experience with an extended-release opioid formulation designed to reduce abuse liability in a community-based pain management clinic. AB - CONTEXT: With the growing public health concern over rising rates of opioid abuse, physicians have a responsibility to incorporate safeguards into their practice to minimize the potential for opioid misuse, abuse, and diversion. Patient-specific treatment regimens should include steps to monitor treatment success with regard to optimal pain management as well as inappropriate use of opioids and other substances. Opioid formulations designed to be less attractive for abuse are also being developed. While future studies are needed to determine the impact of such formulations in addressing the issue of opioid misuse in the community as a whole, the experience of practitioners who have utilized these formulations can highlight the practical steps to incorporate such formulations into the everyday patient-care setting. PURPOSE: The purpose of this report is to describe experience in managing patients with chronic, moderate-to-severe pain using morphine sulfate and naltrexone hydrochloride extended release capsules (MS sNT) (EMBEDA((r)), King Pharmaceuticals((r)) Inc, Bristol, TN, which was acquired by Pfizer Inc, New York, NY, in March 2011), a formulation designed with features to deter abuse/misuse, in a community-based pain management clinic. CASE PRESENTATIONS: Case reports demonstrating a clinical management plan for assessment, initial interview procedures, explanation/discussion of proposed therapies, patients' treatment goals, conversion to MS-sNT, and titration and treatment outcomes are provided. RESULTS: The management approach yielded successful outcomes including pain relief, improved quality of life, treatment satisfaction, and patient acceptance of a formulation designed to deter abuse/misuse. DISCUSSION: The cases presented demonstrate that the communication accompanying complete pretreatment assessment, goal-setting and expectations, and attention to individual patient needs can enable optimization of pain-related outcomes, resulting in improved quality of life for patients and fostering patient acceptance of formulations designed to help address opioid abuse/misuse issues in the community at large. PMID- 22069368 TI - Noninvasive radioelectric asymmetric brain stimulation in the treatment of stress related pain and physical problems: psychometric evaluation in a randomized, single-blind placebo-controlled, naturalistic study. AB - BACKGROUND: The aim of this study was to investigate the effects of noninvasive radioelectric asymmetric conveyer brain stimulation (REAC-BS) on pain and physical problems, a measurement cluster of the Psychological Stress Measure (PSM) test. When the symptoms of pain and physical problems do not respond to various therapeutic approaches such as medication, physiotherapy, and psychotherapy, they are often called medically unexplained symptoms. As such, these symptoms are reported to be a response to stressful situations or emotional states, often unknown to patients themselves. To explore the effectiveness of noninvasive radioelectric brain stimulation in the amelioration of symptoms of pain and physical problems, we administered a neuropsychophysical optimization protocol using a REAC device. METHODS: The PSM, a self-administered questionnaire, was used to measure psychological stress and pain and physical problems in a group of 888 subjects. Data were collected immediately prior to and following a 4-week REAC treatment cycle. RESULTS: There was a significant reduction in scores measuring subjective perceptions of stress for subjects treated with one cycle of neuropsychophysical optimization REAC-BS. At the end of the study, the number of treated subjects reporting symptoms of stress-related pain and physical problems on the PSM test was significantly reduced, whereas there was no difference in placebo-treated subjects. CONCLUSION: One cycle of neuropsychophysical optimization REAC-BS appears to reduce subjective perceptions of stress as measured by the PSM, particularly on the pain and physical problems cluster. PMID- 22069369 TI - Acute renal failure and severe rhabdomyolysis in a patient with resistant thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder. This paper describes the case of a 39-year-old Sudanese male who presented to the emergency room with fever, jaundice, decreased level of consciousness, and worsening kidney function for 7 days, a high lactate dehydrogenase level (1947), severe thrombocytopenia (platelets 8), and numerous schistocytes in the peripheral blood smear. The patient was admitted with a diagnosis of TTP for plasma exchange. Fourteen days later, his creatinine kinase (CK) level rose to >50,000 IU; rhabdomyolysis was suggested. Continuous venovenous hemodialysis (CVVHD) was started. The patient's CK level remained high, despite CVVHD, until the 6th day, after which this parameter gradually started to decrease. This report highlights a resistant case of TTP that presented with concomitant severe rhabdomyolysis, which demanded aggressive, continuous intervention. PMID- 22069370 TI - Chronic productive cough and extensive cysts in left lung. AB - Bronchiectasis refers to dilated and thickened airways due to chronic inflammation and infections, with anatomic distortion of the bronchi. Here, we describe a 29-year-old man with a history of multiple hospitalizations for lung infection who presented to the pulmonary clinic with a complaint of worsening chronic productive cough in the previous year. This case presentation prompted a review of the etiologies of bronchiectasis in 291 recent cases admitted to Masih Daneshvari Hospital, Tehran. PMID- 22069371 TI - Exploitation of resources and cardiovascular outcomes in low-risk patients with chest pain hospitalized in coronary care units. AB - BACKGROUND: Most patients who present to medical centers due to chest pain do not suffer from acute coronary syndromes and do not need to be hospitalized in coronary care units (CCUs). This study was done to determine exploitation of resources and cardiovascular outcomes in low-risk patients with chest pain hospitalized in CCUs of educational hospitals affiliated with a major medical university. METHODS: Over a 4-month period, 550 patients with chest pain who were hospitalized in the CCUs belonging to six hospitals affiliated to the authors' medical university were recruited by census method. Using Thrombolysis in Myocardial Infarction risk score, 95 patients (17.27%) were categorized as low risk patients. This group was evaluated with respect to demographics, bed occupancy rate, mean hospitalization period, expenses during admission, and cardiovascular outcomes in the 30-day period postdischarge. RESULTS: Mean (+/- standard deviation) hospitalization duration was 3.04 (+/-0.71) days. No significant difference was seen between the six surveyed hospitals regarding hospitalization duration (P = 0.602). The highest bed occupancy rate was seen in Taleghani and Shohada Tajrish hospitals and the lowest was in Modarres Hospital. The mean paid treatment expenses by low-risk patients was IRR 2,050,000 (US$205). Mean total hospitalization expenses was US$205. No significant difference was seen between the six surveyed hospitals (P = 0.699). Of the patients studied, 89.5% did not show any cardiovascular complications in 1 month and no deaths occurred. CONCLUSION: Given the high bed-occupancy rate by low-risk patients, associated high hospitalization costs, and the lack of cardiovascular complications in patients observed at 1-month follow-up after discharge, it is recommended that appropriate evaluations be performed in emergency units to prevent unnecessary admissions. PMID- 22069372 TI - The burden of cancer risk in Canada's indigenous population: a comparative study of known risks in a Canadian region. AB - BACKGROUND: Canadian First Nations, the largest of the Aboriginal groups in Canada, have had lower cancer incidence and mortality rates than non-Aboriginal populations in the past. This pattern is changing with increased life expectancy, a growing population, and a poor social environment that influences risk behaviors, metabolic conditions, and disparities in screening uptake. These factors alone do not fully explain differences in cancer risk between populations, as genetic susceptibility and environmental factors also have significant influence. However, genetics and environment are difficult to modify. This study compared modifiable behavioral risk factors and metabolic-associated conditions for men and women, and cancer screening practices of women, between First Nations living on-reserve and a non-First Nations Manitoba rural population (Canada). METHODS: The study used data from the Canadian Community Health Survey and the Manitoba First Nations Regional Longitudinal Health Survey to examine smoking, binge drinking, metabolic conditions, physical activity, fruit/vegetable consumption, and cancer-screening practices. RESULTS: First Nations on-reserve had significantly higher rates of smoking (P < 0.001), binge drinking (P < 0.001), obesity (P < 0.001) and diabetes (P < 0.001), and less leisure-time physical activity (P = 0.029), and consumption of fruits and vegetables (P < 0.001). Sex differences were also apparent. In addition, First Nations women reported significantly less uptake of mammography screening (P < 0.001) but similar rates for cervical cancer screening. CONCLUSIONS: Based on the findings of this retrospective study, the future cancer burden is expected to be high in the First Nations on-reserve population. Interventions, utilizing existing and new health and social authorities, and long-term institutional partnerships, are required to combat cancer risk disparities, while governments address economic disparities. PMID- 22069373 TI - Exercise lowers blood pressure in university professors during subsequent teaching and sleeping hours. AB - BACKGROUND: University professors are subjected to psychological stress that contributes to blood pressure (BP) reactivity and development of hypertension. The purpose of this study was to investigate the effects of exercise on BP in university professors during teaching and sleeping hours. METHODS: Twelve normotensive professors (42.2 +/- 10.8 years, 74.2 +/- 11.2 kg, 172.8 +/- 10.4 cm, 20.1% +/- 6.7% body fat) randomly underwent control (CONT) and exercise (EX30) sessions before initiating their daily activities. EX30 consisted of 30 minutes of cycling at 80%-85% of heart rate reserve. Ambulatory BP was monitored for 24 hours following both sessions. RESULTS: BP increased in comparison with pre-session resting values during teaching after CONT (P < 0.05) but not after EX30. Systolic, diastolic, and mean arterial BP showed a more pronounced nocturnal dip following EX30 (approximately -14.7, -12.7, and -9.6 mmHg, respectively) when compared with CONT (approximately -6, -5 and -3 mmHg). CONCLUSION: Exercise induced a BP reduction in university professors, with the main effects being observed during subsequent teaching and sleeping hours. PMID- 22069374 TI - Molecular pathogenesis of EBV susceptibility in XLP as revealed by analysis of female carriers with heterozygous expression of SAP. AB - X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency caused by mutations in SH2D1A which encodes SAP. SAP functions in signalling pathways elicited by the SLAM family of leukocyte receptors. A defining feature of XLP is exquisite sensitivity to infection with EBV, a B-lymphotropic virus, but not other viruses. Although previous studies have identified defects in lymphocytes from XLP patients, the unique role of SAP in controlling EBV infection remains unresolved. We describe a novel approach to this question using female XLP carriers who, due to random X-inactivation, contain both SAP(+) and SAP(-) cells. This represents the human equivalent of a mixed bone marrow chimera in mice. While memory CD8(+) T cells specific for CMV and influenza were distributed across SAP(+) and SAP(-) populations, EBV-specific cells were exclusively SAP(+). The preferential recruitment of SAP(+) cells by EBV reflected the tropism of EBV for B cells, and the requirement for SAP expression in CD8(+) T cells for them to respond to Ag-presentation by B cells, but not other cell types. The inability of SAP(-) clones to respond to Ag-presenting B cells was overcome by blocking the SLAM receptors NTB-A and 2B4, while ectopic expression of NTB-A on fibroblasts inhibited cytotoxicity of SAP(-) CD8(+) T cells, thereby demonstrating that SLAM receptors acquire inhibitory function in the absence of SAP. The innovative XLP carrier model allowed us to unravel the mechanisms underlying the unique susceptibility of XLP patients to EBV infection in the absence of a relevant animal model. We found that this reflected the nature of the Ag-presenting cell, rather than EBV itself. Our data also identified a pathological signalling pathway that could be targeted to treat patients with severe EBV infection. This system may allow the study of other human diseases where heterozygous gene expression from random X-chromosome inactivation can be exploited. PMID- 22069376 TI - Unique interplay between sugar and lipid in determining the antigenic potency of bacterial antigens for NKT cells. AB - Invariant natural killer T (iNKT) cells are an evolutionary conserved T cell population characterized by features of both the innate and adaptive immune response. Studies have shown that iNKT cells are required for protective responses to Gram-positive pathogens such as Streptococcus pneumoniae, and that these cells recognize bacterial diacylglycerol antigens presented by CD1d, a non classical antigen-presenting molecule. The combination of a lipid backbone containing an unusual fatty acid, vaccenic acid, as well as a glucose sugar that is weaker or not stimulatory when linked to other lipids, is required for iNKT cell stimulation by these antigens. Here we have carried out structural and biophysical studies that illuminate the reasons for the stringent requirement for this unique combination. The data indicate that vaccenic acid bound to the CD1d groove orients the protruding glucose sugar for TCR recognition, and it allows for an additional hydrogen bond of the glucose with CD1d when in complex with the TCR. Furthermore, TCR binding causes an induced fit in both the sugar and CD1d, and we have identified the CD1d amino acids important for iNKT TCR recognition and the stability of the ternary complex. The studies show also how hydrogen bonds formed by the glucose sugar can account for the distinct binding kinetics of the TCR for this CD1d-glycolipid complex. Therefore, our studies illuminate the mechanism of glycolipid recognition for antigens from important pathogens. PMID- 22069375 TI - De novo genesis of enhancers in vertebrates. AB - Evolutionary innovation relies partially on changes in gene regulation. While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates. For this, we took advantage of the massive gene loss following the last whole genome duplication in teleosts to systematically identify regions that have lost their coding capacity but retain sequence conservation with mammals. We found that these regions show enhancer activity while the orthologous coding regions have no regulatory activity. These results demonstrate that these enhancers have been de novo generated in fish. By revealing that minor changes in non-regulatory sequences are sufficient to generate new enhancers, our study highlights an important playground for creating new regulatory variability and evolutionary innovation. PMID- 22069377 TI - On the futility of screening for genes that make you fat. PMID- 22069378 TI - Priorities for research on equity and health: towards an equity-focused health research agenda. PMID- 22069380 TI - Cholinergic partition cells and lamina x neurons induce a muscarinic-dependent short-term potentiation of commissural glutamatergic inputs in lumbar motoneurons. AB - Acetylcholine and the activation of muscarinic receptors influence the activity of neural networks generating locomotor behavior in the mammalian spinal cord. Using electrical stimulations of the ventral commissure, we show that commissural muscarinic (CM) depolarizations could be induced in lumbar motoneurons. We provide a detailed electrophysiological characterization of the muscarinic receptors and the membrane conductance involved in these responses. Activation of the CM terminals, originating from lamina X neurons and partition cells, induced a pathway-specific short-term potentiation (STP) of commissural glutamatergic inputs in motoneurons. This STP is occluded in the presence of the muscarinic antagonist atropine. During fictive locomotion, the activation of the commissural pathways transiently enhanced the motor output in a muscarinic-dependent manner. This study describes for the first time a novel regulatory mechanism of synaptic strength in spinal locomotor networks. Such cellular mechanisms would endow the locomotor central pattern generators with adaptive processes needed to generate appropriate synaptic inputs to motoneurons during different motor tasks. PMID- 22069381 TI - Topographic Organization and Corticocortical Connections of the Forepaw Representation in Areas S1 and SC of the Opossum: Evidence for a Possible Role of Area SC in Multimodal Processing. AB - In small-brained mammals, such as opossums, the cortex is organized in fewer sensory and motor areas than in mammals endowed with larger cortical sheets. The presence of multimodal fields, involved in the integration of sensory inputs has not been clearly characterized in those mammals. In the present study, the corticocortical connections of the forepaw representation in the somatosensory caudal (SC) area of the Didelphis aurita opossum was studied with injections of fluorescent anatomical tracers in SC. Electrophysiological mapping of S1 was used to delimit its respective rostral and caudal borders, and to guide SC injections. The areal borders of S1 and the location of area SC were further confirmed by myeloarchitecture. In S1, we found a well-delimited forepaw representation, although it presented a crude internal topographic organization. Cortical projections to S1 originate in somatosensory areas of the parietal cortex, and appeared to be mostly homotopic. Physiological and connectional evidence were provided for a topographic organization in opossum area SC as well. Most notably, corticocortical projections to the forepaw representation of SC originated from somatosensory cortical areas and from cortex representing other sensory modalities, especially the visual peristriate cortex. This suggests that SC might be involved in multimodal processing similar to the posterior parietal cortex of species with larger brains. PMID- 22069379 TI - Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. AB - BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO*PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity. PMID- 22069382 TI - Can Temporal Repetitive Transcranial Magnetic Stimulation be Enhanced by Targeting Affective Components of Tinnitus with Frontal rTMS? A Randomized Controlled Pilot Trial. AB - OBJECTIVES: Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex has been investigated as a new treatment tool for chronic tinnitus during the last years and has shown moderate efficacy. However, there is growing evidence that tinnitus is not a pathology of a specific brain region, but rather the result of network dysfunction involving both auditory and non-auditory brain regions. In functional imaging studies the right dorsolateral prefrontal cortex has been identified as an important hub in tinnitus related networks and has been shown to particularly reflect the affective components of tinnitus. Based on these findings we aimed to investigate whether the effects of left low frequency rTMS can be enhanced by antecedent right prefrontal low-frequency rTMS. STUDY DESIGN: Fifty-six patients were randomized to receive either low-frequency left temporal rTMS or a combination of low-frequency right prefrontal followed by low-frequency left temporal rTMS. The change of the tinnitus questionnaire (TQ) score was the primary outcome, secondary outcome parameters included the Tinnitus Handicap Inventory, numeric rating scales, and the Beck Depression Inventory. The study is registered in clinicaltrials.gov (NCT01261949). RESULTS: Directly after therapy there was a significant improvement of the TQ-score in both groups. Comparison of both groups revealed a trend toward more pronounced effects for the combined group (effect size: Cohen's d = 0.176), but this effect did not reach significance. A persistent trend toward better efficacy was also observed in all other outcome criteria. CONCLUSION: Additional stimulation of the right prefrontal cortex seems to be a promising strategy for enhancing TMS effects over the temporal cortex. These results further support the involvement of the right DLPFC in the pathophysiology of tinnitus. The small effect size might be due to the study design comparing the protocol to an active control condition. PMID- 22069383 TI - Computational characterization of visually induced auditory spatial adaptation. AB - Recent research investigating the principles governing human perception has provided increasing evidence for probabilistic inference in human perception. For example, human auditory and visual localization judgments closely resemble that of a Bayesian causal inference observer, where the underlying causal structure of the stimuli are inferred based on both the available sensory evidence and prior knowledge. However, most previous studies have focused on characterization of perceptual inference within a static environment, and therefore, little is known about how this inference process changes when observers are exposed to a new environment. In this study we aimed to computationally characterize the change in auditory spatial perception induced by repeated auditory-visual spatial conflict, known as the ventriloquist aftereffect. In theory, this change could reflect a shift in the auditory sensory representations (i.e., shift in auditory likelihood distribution), a decrease in the precision of the auditory estimates (i.e., increase in spread of likelihood distribution), a shift in the auditory bias (i.e., shift in prior distribution), or an increase/decrease in strength of the auditory bias (i.e., the spread of prior distribution), or a combination of these. By quantitatively estimating the parameters of the perceptual process for each individual observer using a Bayesian causal inference model, we found that the shift in the perceived locations after exposure was associated with a shift in the mean of the auditory likelihood functions in the direction of the experienced visual offset. The results suggest that repeated exposure to a fixed auditory-visual discrepancy is attributed by the nervous system to sensory representation error and as a result, the sensory map of space is recalibrated to correct the error. PMID- 22069384 TI - Revealing context-specific conditioned fear memories with full immersion virtual reality. AB - The extinction of conditioned fear is known to be context-specific and is often considered more contextually bound than the fear memory itself (Bouton, 2004). Yet, recent findings in rodents have challenged the notion that contextual fear retention is initially generalized. The context-specificity of a cued fear memory to the learning context has not been addressed in the human literature largely due to limitations in methodology. Here we adapt a novel technology to test the context-specificity of cued fear conditioning using full immersion 3-D virtual reality (VR). During acquisition training, healthy participants navigated through virtual environments containing dynamic snake and spider conditioned stimuli (CSs), one of which was paired with electrical wrist stimulation. During a 24-h delayed retention test, one group returned to the same context as acquisition training whereas another group experienced the CSs in a novel context. Unconditioned stimulus expectancy ratings were assayed on-line during fear acquisition as an index of contingency awareness. Skin conductance responses time locked to CS onset were the dependent measure of cued fear, and skin conductance levels during the interstimulus interval were an index of context fear. Findings indicate that early in acquisition training, participants express contingency awareness as well as differential contextual fear, whereas differential cued fear emerged later in acquisition. During the retention test, differential cued fear retention was enhanced in the group who returned to the same context as acquisition training relative to the context shift group. The results extend recent rodent work to illustrate differences in cued and context fear acquisition and the contextual specificity of recent fear memories. Findings support the use of full immersion VR as a novel tool in cognitive neuroscience to bridge rodent models of contextual phenomena underlying human clinical disorders. PMID- 22069385 TI - Broader visual orientation tuning in patients with schizophrenia. AB - Reduced gamma-aminobutyric acid (GABA) levels in cerebral cortex are thought to contribute to information processing deficits in patients with schizophrenia (SZ), and we have previously reported lower in vivo GABA levels in the visual cortex of patients with SZ. GABA-mediated inhibition plays a role in sharpening orientation tuning of visual cortical neurons. Therefore, we predicted that tuning for visual stimulus orientation would be wider in SZ. We measured orientation tuning with a psychophysical procedure in which subjects performed a target detection task of a low-contrast oriented grating, following adaptation to a high-contrast grating. Contrast detection thresholds were determined for a range of adapter-target orientation offsets. For both SZ and healthy controls, contrast thresholds decreased as orientation offset increased, suggesting that this tuning curve reflects the selectivity of visual cortical neurons for stimulus orientation. After accounting for generalized deficits in task performance in SZ, there was no difference between patients and controls for detection of target stimuli having either the same orientation as the adapter or orientations far from the adapter. However, patients' thresholds were significantly higher for intermediate adapter-target offsets. In addition, the mean width parameter of a Gaussian fit to the psychophysical orientation tuning curves was significantly larger for the patient group. We also present preliminary data relating visual cortical GABA levels, as measured with magnetic resonance spectroscopy, and orientation tuning width. These results suggest that our finding of broader orientation tuning in SZ may be due to diminished visual cortical GABA levels. PMID- 22069386 TI - Increased readiness for adaptation and faster alternation rates under binocular rivalry in children. AB - Binocular rivalry in childhood has been poorly investigated in the past. Information is scarce with respect to infancy, and there is a complete lack of data on the development of binocular rivalry beyond the first 5-6 years of age. In this study, we are attempting to fill this gap by investigating the developmental trends in binocular rivalry in pre-puberty. We employ a classic behavioral paradigm with orthogonal gratings, and introduce novel statistical measures (after Pastukhov and Braun) to analyze the data. These novel measures provide a sensitive tool to estimate the impact of the history of perceptual dominance on future alternations. We found that the cumulative history of perceptual alternations has an impact on future percepts, and that this impact is significantly stronger and faster in children than in adults. Assessment of the "cumulative history" and its characteristic time-constant helps us to take a look at the adaptive states of the visual system under multi-stable perception, and brings us closer to establishing a possible developmental scenario of binocular rivalry: a greater and faster relative contribution of neural adaptation is found in children, and this increased readiness for adaption seems to be associated with faster alternation rates. PMID- 22069387 TI - Brain correlates of mathematical competence in processing mathematical representations. AB - The ability to extract numerical information from different representation formats (e.g., equations, tables, or diagrams) is a key component of mathematical competence but little is known about its neural correlate. Previous studies comparing mathematically less and more competent adults have focused on mental arithmetic and reported differences in left angular gyrus (AG) activity which were interpreted to reflect differential reliance on arithmetic fact retrieval during problem solving. The aim of the present functional magnetic resonance imaging study was to investigate the brain correlates of mathematical competence in a task requiring the processing of typical mathematical representations. Twenty-eight adults of lower and higher mathematical competence worked on a representation matching task in which they had to evaluate whether the numerical information of a symbolic equation matches that of a bar chart. Two task conditions without and one condition with arithmetic demands were administered. Both competence groups performed equally well in the non-arithmetic conditions and only differed in accuracy in the condition requiring calculation. Activation contrasts between the groups revealed consistently stronger left AG activation in the more competent individuals across all three task conditions. The finding of competence-related activation differences independently of arithmetic demands suggests that more and less competent individuals differ in a cognitive process other than arithmetic fact retrieval. Specifically, it is argued that the stronger left AG activity in the more competent adults may reflect their higher proficiency in processing mathematical symbols. Moreover, the study demonstrates competence-related parietal activation differences that were not accompanied by differential experimental performance. PMID- 22069388 TI - Sensory feedback plays a significant role in generating walking gait and in gait transition in salamanders: a simulation study. AB - Here, we investigate the role of sensory feedback in gait generation and transition by using a three-dimensional, neuro-musculo-mechanical model of a salamander with realistic physical parameters. Activation of limb and axial muscles were driven by neural output patterns obtained from a central pattern generator (CPG) which is composed of simulated spiking neurons with adaptation. The CPG consists of a body-CPG and four limb-CPGs that are interconnected via synapses both ipsilaterally and contralaterally. We use the model both with and without sensory modulation and four different combinations of ipsilateral and contralateral coupling between the limb-CPGs. We found that the proprioceptive sensory inputs are essential in obtaining a coordinated lateral sequence walking gait (walking). The sensory feedback includes the signals coming from the stretch receptor like intraspinal neurons located in the girdle regions and the limb stretch receptors residing in the hip and scapula regions of the salamander. On the other hand, walking trot gait (trotting) is more under central (CPG) influence compared to that of the peripheral or sensory feedback. We found that the gait transition from walking to trotting can be induced by increased activity of the descending drive coming from the mesencephalic locomotor region and is helped by the sensory inputs at the hip and scapula regions detecting the late stance phase. More neurophysiological experiments are required to identify the precise type of mechanoreceptors in the salamander and the neural mechanisms mediating the sensory modulation. PMID- 22069389 TI - Affective infrastructures: toward a cultural neuropsychology of sport. AB - Recently there has been a turn toward considerations of embodiment, cognition, and context in sport studies. Many researchers have argued that the traditional focus on clinical psychology and performance enhancement within the discipline is incomplete, and now emphasize the importance of athletes' social and familial contexts in a research paradigm that examines interconnections between movement, cognition, emotion, and the social and cultural context in which movement takes place. While it is important that the sport studies focus is being expanded to consider these interactions, I will argue that this model is still incomplete in that it is missing a fundamental variable - that of our evolutionary neurobiological roots. I will use the work of affective neuroscientists Jaak Panksepp and Stephen Porges to show that because sport so clearly activates neural systems that function at both proximate and ultimate levels of causation, it can be seen to serve fundamental needs for affective balance. A neurobiology of affect shows how the evolution of the mammalian autonomic nervous system has resulted in neurophysiological substrates for affective processes and stress responses, and has wide-ranging implications for sport studies in terms of suggesting what forms of coaching might be the most effective in what context. I propose the term cultural neuropsychology of sport as a descriptor for a model that examines the relationships between neurophysiological substrates and athletes' social and familial contexts in terms of how these variables facilitate or fail to facilitate athletes' neuroceptions of safety, which in turn have a direct impact on their performance. A cultural neuropsychological model of sport might thereby be seen to elaborate a relationship between proximate and ultimate mechanisms in concretely applied ways. PMID- 22069390 TI - Information domain approach to the investigation of cardio-vascular, cardio pulmonary, and vasculo-pulmonary causal couplings. AB - The physiological mechanisms related to cardio-vascular (CV), cardio-pulmonary (CP), and vasculo-pulmonary (VP) regulation may be probed through multivariate time series analysis tools. This study applied an information domain approach for the evaluation of non-linear causality to the beat-to-beat variability series of heart period (t), systolic arterial pressure (s), and respiration (r) measured during tilt testing and paced breathing (PB) protocols. The approach quantifies the causal coupling from the series i to the series j (C(ij)) as the amount of information flowing from i to j. A measure of directionality is also obtained as the difference between two reciprocal causal couplings (D(i,j) = C(ij) - C(ji)). Significant causal coupling and directionality were detected respectively when the median of C(ij) over subjects was positive (C(ij) > 0), and when D(i,j) was statistically different from zero (D(i,j) > 0 or D(i,j) < 0). The method was applied on t, s, and r series measured in 15 healthy subjects (22-32 years, 8 males) in the supine (su) and upright (up) positions, and in further 15 subjects (21-29 years, 7 males) during spontaneous (sp) and paced (pa) breathing. In the control condition (su, sp), a significant causal coupling was observed for C(rs), C(rt), C(st), and C(ts), and significant directionality was present only from r to t (D(r,t) > 0). During head-up tilt (up, sp), C(rs) was preserved, C(rt) decreased to zero median, and C(st) and C(ts) increased significantly; directionality vanished between r and t (D(r,t) = 0) and raised from s to t (D(s,t) > 0). During PB (su, pa), C(rs) increased significantly, C(rt) and C(ts) were preserved, and C(st) decreased to zero median; directionality was preserved from r to t (D(r,t) > 0), and raised from r to s (D(r,s) > 0). These results suggest that the approach may reflect modifications of CV, CP, and VP mechanisms consequent to altered physiological conditions, such as the baroreflex engagement and the dampening of respiratory sinus arrhythmia induced by tilt, or the respiratory driving on arterial pressure induced by PB. Thus, it could be suggested as a tool for the non-invasive monitoring of CV and cardiorespiratory control systems in normal and impaired conditions. PMID- 22069391 TI - Oxytocin receptor gene associated with the efficiency of social auditory processing. AB - Oxytocin has been shown to facilitate social aspects of sensory processing, thereby enhancing social communicative behaviors and empathy. Here we report that compared to the AA/AG genotypes, the presumably more efficient GG genotype of an oxytocin receptor gene polymorphism (OXTR rs53576) that has previously been associated with increased sensitivity of social processing is related to less self-reported difficulty in hearing and understanding people when there is background noise. The present result extends associations between oxytocin and social processing to the auditory and vocal domain. We discuss the relevance of our findings for autistic spectrum disorders (ASD), as ASD seems related to specific impairments in the orienting to, and selection of speech sounds from background noise, and some social processing impairments in patients with ASD have been found responsive to oxytocin treatment. PMID- 22069392 TI - Finger numeral representations: more than just another symbolic code. PMID- 22069393 TI - Attention demands of spoken word planning: a review. AB - Attention and language are among the most intensively researched abilities in the cognitive neurosciences, but the relation between these abilities has largely been neglected. There is increasing evidence, however, that linguistic processes, such as those underlying the planning of words, cannot proceed without paying some form of attention. Here, we review evidence that word planning requires some but not full attention. The evidence comes from chronometric studies of word planning in picture naming and word reading under divided attention conditions. It is generally assumed that the central attention demands of a process are indexed by the extent that the process delays the performance of a concurrent unrelated task. The studies measured the speed and accuracy of linguistic and non linguistic responding as well as eye gaze durations reflecting the allocation of attention. First, empirical evidence indicates that in several task situations, processes up to and including phonological encoding in word planning delay, or are delayed by, the performance of concurrent unrelated non-linguistic tasks. These findings suggest that word planning requires central attention. Second, empirical evidence indicates that conflicts in word planning may be resolved while concurrently performing an unrelated non-linguistic task, making a task decision, or making a go/no-go decision. These findings suggest that word planning does not require full central attention. We outline a computationally implemented theory of attention and word planning, and describe at various points the outcomes of computer simulations that demonstrate the utility of the theory in accounting for the key findings. Finally, we indicate how attention deficits may contribute to impaired language performance, such as in individuals with specific language impairment. PMID- 22069394 TI - In search of our true selves: feedback as a path to self-knowledge. AB - How can self-knowledge of personality be improved? What path is the most fruitful source for learning about our true selves? Previous research has noted two main avenues for learning about the self: looking inward (e.g., introspection) and looking outward (e.g., feedback). Although most of the literature on these topics does not directly measure the accuracy of self-perceptions (i.e., self knowledge), we review these paths and their potential for improving self knowledge. We come to the conclusion that explicit feedback, a largely unexamined path, is likely a fruitful avenue for learning about one's own personality. Specifically, we suggest that self-knowledge might be fully realized through the use of explicit feedback from close, knowledgeable others. As such, we conclude that the road to self-knowledge likely cannot be traveled alone but must be traveled with close others who can help shed light on our blind spots. PMID- 22069395 TI - False Belief vs. False Photographs: A Test of Theory of Mind or Working Memory? AB - Theory of mind (ToM), the ability to reason about other people's thoughts and beliefs, has been traditionally studied in behavioral and neuroimaging experiments by comparing performance in "false belief" and "false photograph" (control) stories. However, some evidence suggests that these stories are not matched in difficulty, complicating the interpretation of results. Here, we more fully evaluated the relative difficulty of comprehending these stories and drawing inferences from them. Subjects read false belief and false photograph stories followed by comprehension questions that probed true ("reality" questions) or false beliefs ("representation" questions) appropriate to the stories. Stories and comprehension questions were read and answered, respectively, more slowly in the false photograph than false belief conditions, indicating their greater difficulty. Interestingly, accuracy on representation questions for false photograph stories was significantly lower than for all other conditions and correlated positively with participants' working memory span scores. These results suggest that drawing representational inferences from false photo stories is particularly difficult and places heavy demands on working memory. Extensive naturalistic practice with ToM reasoning may enable a more flexible and efficient mental representation of false belief stories, resulting in lower memory load requirements. An important implication of these results is that the differential modulation of right temporal-parietal junction (RTPJ) during ToM and "false photo" control conditions may reflect the documented negative correlation of RTPJ activity with working memory load rather than a specialized involvement in ToM processes. PMID- 22069397 TI - Examination of microbial proteome preservation techniques applicable to autonomous environmental sample collection. AB - Improvements in temporal and spatial sampling frequency have the potential to open new windows into the understanding of marine microbial dynamics. In recent years, efforts have been made to allow automated samplers to collect microbial biomass for DNA/RNA analyses from moored observatories and autonomous underwater vehicles. Measurements of microbial proteins are also of significant interest given their biogeochemical importance as enzymes that catalyze reactions and transporters that interface with the environment. We examined the influence of five preservatives solutions (SDS-extraction buffer, ethanol, trichloroacetic acid, B-PER, and RNAlater) on the proteome integrity of the marine cyanobacterium Synechococcus WH8102 after 4 weeks of storage at room temperature. Four approaches were used to assess degradation: total protein recovery, band integrity on an SDS detergent polyacrylamide electrophoresis (SDS-PAGE) gel, and number of protein identifications and relative abundances by 1-dimensional LC MS/MS proteomic analyses. Total protein recoveries from the preserved samples were lower than the frozen control due to processing losses, which could be corrected for with internal standardization. The trichloroacetic acid preserved sample showed significant loss of protein band integrity on the SDS-PAGE gel. The RNAlater preserved sample showed the highest number of protein identifications (103% relative to the control; 520 +/- 31 identifications in RNAlater versus 504 +/- 4 in the control), equivalent to the frozen control. Relative abundances of individual proteins in the RNAlater treatment were quite similar to that of the frozen control (average ratio of 1.01 +/- 0.27 for the 50 most abundant proteins), while the SDS-extraction buffer, ethanol, and B-PER all showed significant decreases in both number of identifications and relative abundances of individual proteins. Based on these findings, RNAlater was an effective proteome preservative, although further study is warranted on additional marine microbes. PMID- 22069396 TI - Phonological Planning during Sentence Production: Beyond the Verb. AB - The current study addresses the extent of phonological planning during spontaneous sentence production. Previous work shows that at articulation, phonological encoding occurs for entire phrases, but encoding beyond the initial phrase may be due to the syntactic relevance of the verb in planning the utterance. I conducted three experiments to investigate whether phonological planning crosses multiple grammatical phrase boundaries (as defined by the number of lexical heads of phrase) within a single phonological phrase. Using the picture-word interference paradigm, I found in two separate experiments a significant phonological facilitation effect to both the verb and noun of sentences like "He opens the gate." I also altered the frequency of the direct object and found longer utterance initiation times for sentences ending with a low-frequency vs. high-frequency object offering further support that the direct object was phonologically encoded at the time of utterance initiation. That phonological information for post-verbal elements was activated suggests that the grammatical importance of the verb does not restrict the extent of phonological planning. These results suggest that the phonological phrase is unit of planning, where all elements within a phonological phrase are encoded before articulation. Thus, consistent with other action sequencing behavior, there is significant phonological planning ahead in sentence production. PMID- 22069398 TI - Lived experience of infertile men with male infertility cause. AB - BACKGROUND: Approximately 15 percent of all the couples are involuntarily childless in reproductive ages. The ability to reproduce and give birth to a child is an important part of the human beings life; thus, infertility can cause anxiety for the infertile people. Therefore, this study aimed to investigate men's experiences from male infertility. METHODS: This was a descriptive phenomenological study. The data were collected using in-depth interview of ten infertile men. The interviews were taped and then transcribed on the paper for analyzing through seven-step Colaizzi method. Considering that in qualitative studies, study population is not considered, therefore there was no limitation in location for collecting the data and the participants selected from the infertile men of the society. RESULTS: FOUR MAIN CONCEPTS WERE OBTAINED IN ASSOCIATION WITH INFERTILITY PHENOMENON: individual stress, challenges in communication, problems associated with treatment process and the effects of beliefs and religious attitude. CONCLUSIONS: According to the results of this study, it seems that all the different life aspects of infertile were affected by infertility. Thus, designing and conducting conductive and supportive programs plays an important role for providing better care for infertile men. PMID- 22069399 TI - Assessing the nursing error rate and related factors from the view of nursing staff. AB - BACKGROUND: Error is an inevitable aspect of all the professions particularly health and treatment-related jobs and it should be acknowledged that committing it cannot absolutely be preventable. Among the causes that necessitate the evaluation of nursing errors, it should be noted that errors not only lead to damage and mortality for the patients, but also they are one of the obvious and costly problems in the hospitals. It is believed that nurses have the focal role in committing nursing errors.The main objective of this study was to identify nursing errors and the related factors. METHODS: This was a descriptive correlative study which was conducted in 2010. 239 nurses and head nurses who were working in the selected hospitals in Isfahan were selected randomly and participated in this research. In order to collect the data, two questionnaires were used, each one consisting of three sections of the demographic data, questions about the type of error and the effective factors for making the errors. RESULTS: The highest rate of error was reported about the lack of compiling and reviewing the medical history of the patient (31.75%) and also disregarding the appropriate time for prescription of the medicine (31.75%). Besides, the nurses and head nurses believed in more than one factor for committing the errors and mentioned the managerial factors (84.2%) and patient related factors (50.5%) as the most important and the least important causes for the commitment of errors respectively. Moreover, there was a direct relationship between gender, ward, and having an extra job with the score of the nursing errors. CONCLUSIONS: Attempts for reducing and controlling the nursing errors can rely on the usage of systemic approaches for assessing the effective factors, removing these factors as much as possible, and designing a system for increasing the level of reporting these errors for identifying the weak points and jeopardizing factors. PMID- 22069400 TI - Assessing the effect of high school students' training program on peers performance suffering from asthma. AB - BACKGROUND: Asthma is the most common disease in childhood which is considered as the forerunner of the acute diseases and simply can cause disability among the children. Since childhood and adolescence are the most important periods of growth and perfection and incidence of asthma can bring about distortion in this process, the present study done aimed to assess the effect of conducting high school training program on peers' performance with asthma. METHODS: This was a quasi-experimental study in which the performance rate of the students at the time of artificial attack of asthma was directly observed, assessed and compared through demographic data questionnaire and performance assessment check list. Eighty individuals from the second grade of high school students in 2010 in Isfahan City were randomly selected to participate in the present study, among which, 40 individuals were entered in the test group and 40 of them also were placed in the control group. After conducting the training program for the test group, which had been designed both by direct method (in person and face to face by asking and answering and group discussion) and by indirect method (using pamphlet and other educational materials), the level of the training effectiveness was assessed on the students' performance. RESULTS: The findings of the present study indicated that the performance of students at the test group increased from 2.2 (0.6) to 91.8 (1.3) which emphasized that the training program for the young adolescent peers had a positive effect on promoting their health. CONCLUSIONS: Considering the results of the present study and regarding to the importance and role of students as the future makers of the country, and also the cost-effectiveness of the training programs and the positive effect of peers on increasing the level of health among the students with asthma and consequently decreasing the school absence, it obviously seems necessary to generalize and expand these training programs. PMID- 22069401 TI - Reviewing the effect of two methods of educational package and social inoculation on changing the attitudes towards domestic violence against women. AB - BACKGROUND: Domestic violence (DV) is a serious problem all over the world which had been extended to boundaries of countries, economical, cultural and racial classes. 10-69 percent of women are exposed to physical, sexual and emotional violence which has numerous physical and emotional consequences. Therefore, males' attitude towards women is one of the strongest predicting factors of violence against women, so one of the ways to remove the violence against women is to change the men's attitude. Changing the attitude, in the basic stages of the marriage for couples who are not yet involved with marital misunderstandings, will probably influence their future relationships, therefore, the present study reviewed two attitude changing methods of educational package (EP) and social inoculation (SI) which were used to change the attitude among male volunteers participating in the premarital counseling classes. METHODS: This was a semi experimental study aimed to determine the influence of two methods of supplying EP and SI on the change of attitude toward DV against women. The study subjects included male volunteers participating in Isfahan Molla Hadi Sabzevari Premarital Counseling Center, where the attitudes of 183 subjects were investigated primarily using simple sampling method. Ninety-nine subjects who had positive attitude toward DV were selected and then, randomly distributed into three 33 subject groups. The first was SI group, the second was EP supply group and the third was the control group. Data collection tool was an evaluating questionnaire of the attitude toward DV against women which consisted of two parts, demographic data and 34 attitude evaluating questions. Scientific validity was determined by content validity method and scientific reliability was determined using Cronbach's alpha. Analyzing the data was done using descriptive (frequency and mean), analytical statistical methods (paired-t, independent t-tests, ANOVA, Duncan, Kruskal-Wallis and chi-square) and SPSS software. RESULTS: Among 183 participants, 99 of them (54%) had a positive attitude with an average score of 46.5 and 84 of them (45%) with an average score of 29 had a negative attitude toward violence against women. Before the intervention, the highest violence attitude was in emotional, physical and sexual areas, respectively. After the intervention in the inoculation group, the highest attitude changes were in physical, sexual and emotional areas, respectively and in the EP group, in total the attitude changes score after the intervention was significant compared to prior to it, although changes were observed only in physical and sexual areas. In SI group, more attitude changes were occurred than that in EP group. In control group, the attitude score after the intervention had no significant change compared to it before. CONCLUSIONS: Although attitude change has no guaranty for changing the behavior, in order to change the behavior, changing the attitude is required, in which for violence against women, it is better to be started at the beginning of the marital relationship. The SI method has been successfully applied in psychology Sciences and the health programs, but the EP method is not an effective method on its own to change the attitude, so it is better to be accompanied by other methods like group discussion, etc. PMID- 22069402 TI - Evaluation of men's participation in group training of their wives in family planning programs. AB - BACKGROUND: Population growth is still a global concern. In spite of the decrease in population growth and conception rate, Iran and the world population will grow in coming years. Participation of men in contraception interventions to control population growth is of great importance. METHODS: This is a quasi-experimental study, in which the authors provided group training of contraceptive methods to 53 women, and then evaluated the effect of training on the dependent variable of husbands' participation in family planning. The data was gathered using a questionnaire and a checklist, and then was analyzed using SPSS software, by paired t-test. RESULTS: The results indicated that the mean score of knowledge level of the case group members and their husbands changed significantly after the training program (p < 0.001). Also, it was found that 51% of the participants and their husbands used contraceptive methods after the training program. CONCLUSIONS: Considering the results, providing group training for couples to increase the participation rate of men in family planning programs is recommended. PMID- 22069403 TI - Assessing the effect of two praying methods on the life quality of patients suffering from cancer hospitalized at Seyedo Shohada medical center of Isfahan University of Medical Sciences. AB - BACKGROUND: Life quality and its promotional strategies among patients with acute and debilitating diseases, especially cancer, have been considered from a long time ago by medical and nursing societies. One of the methods to promote the patient's life quality is spiritual care which can be in form of prayer. The results of the studies done about the choice of the best praying method for the patients involves a lot of challenges. Thus, the researchers decided to examine the effect of two individual and choral praying methods on the life quality of the cancer-stricken patients. METHODS: The present study was conducted in two staged clinical trial using pre-post test administration in which the researcher examined the effect of two individual and choral praying methods on the life quality of 70 cancer-stricken patients. Data collection to assess the life quality was performed by World Health Organization Brief Life Quality Questionnaire. RESULTS: The current research showed that the life quality score was increased in the individual-choral group after the intervention. Also, comparing the average life quality score in the two groups of individual and choral praying revealed a significant difference in which the quality of life had improved more in the choral praying group than in the individual praying group. CONCLUSIONS: The findings of the present study indicated the positive effect of praying and supplication on the life quality of cancer-stricken patients. Generally, choral praying has a better effect on the life quality of cancer stricken patients compared with praying individually. More studies with a larger sample size are suggested in order to verify the effect of praying on the life quality of cancer-stricken patients. PMID- 22069404 TI - Reviewing the effect of reflexology on the pain and certain features and outcomes of the labor on the primiparous women. AB - BACKGROUND: Reflexology is one of the non-pharmacological pain relief methods, and since it is a non-invasive, inexpensive and applicable technique, it can be used by a skilled and trained midwife. This study aimed to review the effect of reflexology on the pain and outcomes of the labor. METHODS: In this quasi experimental study, 88 primiparous mothers referred to selected hospitals of Isfahan for vaginal delivery were selected using simple random sampling method and then randomized in two groups. Data collection tools were the demographic data questionnaire, profile and outcomes of the labor and the short-form of the McGill Questionnaire for Pain Rating Index (PRI) assessment. The intervention was general and specific reflexology in the active phase of labor. PRI was assessed before the intervention and four times after the intervention (3-5 cm, 6-8 cm and 9-10 cm dilatations and second stage of labor. RESULTS: There was no significant difference between groups before intervention. In the reflexology group, there was a significant difference between the PRI before and after the 4 stages intervention (p < 0.001). PRI was different significantly between studied groups after intervention (p < 0.001). The length of active phase of labor was different significantly between the two groups; but this difference was not significant during the second (p = 0.29), and the third (p = 0.27) stages. The difference between the 1(st) minute and the 5(th) minute Apgar score (p < 0.001) and rate of hemorrhage between the two groups were different significantly (p = 0.02). CONCLUSIONS: Reflexology can lead to decrease in the labor pain. Therefore, regarding to the safety of this technique, it can be replaced as an alternative for pharmacological methods. PMID- 22069405 TI - Proposing a syllabus for the operation room B.S. courses in Iran. AB - BACKGROUND: Education is based upon the knowledge, skills, and attitudes that are required for an occupation, and the changes occurring in the occupations and duties as well as in the ideals and values necessitate constant needs analysis. Furthermore, owing to the transformations in sciences, especially medical sciences, the current syllabus for the operation room courses at associate level will not meet the requirements for operation room personnel in future. Therefore, the syllabus for operation room B.S. was developed and proposed in a research project entitled "Study of the international syllabus for the operation room courses and proposing an appropriate syllabus for the courses in Iran." Since the operation room courses at B.S. level are supposed to be introduced in Iranian universities, we intended to learn about the opinions of other people related to this subject in Iran. METHODS: In this research, a questionnaire was used that contained the syllabus proposed for the operation room B.S. courses, which was the result of a research project entitled "Study of the international syllabus for the operation room courses and proposing an appropriate syllabus for the courses in Iran." To develop this syllabus, 12 heads of the operation room departments in universities across Iran in which the subject matter was being taught at associate level were consulted. RESULTS: The study showed that 14 out of the 53 courses proposed in the syllabus had a desirability level of 100%, 22 courses were desirable at levels of 91-100%, 19 were 75-90% desirable, and no courses had a desirability level less than 75%. After carrying out some modifications to the syllabus, the problems were resolved and the opinions were again asked. When a consensus of greater than 70% was reached, the syllabus for the operation room courses at B.S. level was finalized and proposed. The regulations from the Development, Planning, and Evaluation Office of the Ministry of Health were also followed. CONCLUSIONS: Although all the courses showed a desirability level of greater than 70%, receiving appropriate suggestions about some courses led the research team to carry out major or minor modifications to some of the courses. PMID- 22069406 TI - Assessing the effect of community health nursing care management at home on war worn soldiers' physical problems suffering from spinal cord complications (urinary infection, bedsore). AB - BACKGROUND: Veterans are among the highly-susceptible and highly-esteemed groups of the society. there is no correct, principled, and comprehensive programming with respect to home-nursing care for them. METHODS: In this quasi-experimental study, 26 veterans with spinal cord complications, with a 70-percent damage who were resident of Najaf Abad, Iran were concluded. The data were gathered by a checklist consisted of two parts, the first part included the demographic data and the second part consisted of Para-clinical (clinical findings) assessment of the veterans suffering from urinary infection, laboratorial assessments, and assessing the bedsores. The researcher visited all the veterans and completed the checklist by interviewing them. RESULTS: The mean age of the veterans was 45 (5.1) years and the highest frequency (53.8%) belonged to the age range of 40-44 years. The mean number of the family members was 4.4 people. The veterans who had paraplegia damage included 88.6%. Considering the damage rate, the highest frequency (69.2%) belonged to thoracic vertebra level. all the 26 veterans had been suffering from urinal infection before the managerial intervention; however 20 subjects (76.9%) had urinal infection after the intervention. CONCLUSIONS: It can be stated that pressure wounds are preventable and these caring measures can be offered to susceptible groups of the community in a better and cheaper way if more studies are done with a closer contact and a higher number of samples in addition to have unison among the community-based systems. PMID- 22069407 TI - The effect of participating in the labor preparation classes on maternal vitality and positive affect during the pregnancy and after the labor. AB - BACKGROUND: Pregnant women predispose to physical and emotional diseases. Vitality and positive affect are against the depression and low energetic mood Exercise and physical activities in pregnancy have short and long term consequences for mothers and their growing fetus and affected in mood regulation. Respiratory and relaxation skills could decrease stress, pain and use of analgesics during labor. METHODS: In this study, 117 primigravida and multigravida women (59 women in case and 58 in control groups) were enrolled. Women in case group participated in delivery preparation classes since 20 weeks of pregnancy for 8 sessions. The control group was just received routine pregnancy care. The education was about pregnancy and delivery, physical exercises and relaxation skills. Questionnaires of vitality and positive affect toward the labor were completed three times: before intervention, after the 8(th) session and after delivery to 2 weeks later by an interview. Data analyzed using SPSS16 software and repeated measurement. RESULTS: There was a significant difference in vitality and positive affect regarding type of delivery before and after intervention and after delivery in case group(p < 0.0001).There was no significant difference in vitality and positive affect scores after delivery and after intervention (p < 0.083, p < 0.545). There was significant difference in vitality and positive affect scores regarding between case and control groups after the intervention and after the delivery (p < 0.001, p < 0.0001). CONCLUSIONS: Considering the results of this study, it could be recommended that all pregnant women should contribute in delivery preparation classes to improve their mood, confidence, vitality toward labor. PMID- 22069408 TI - The effect of anger management by nursing staff on violence rate against them in the emergency unit. AB - BACKGROUND: Violence at work is considered as part of the occupational hazards which can affect medical staff and have undesirable effects on quality of patients care. Anger management training causes increases the ability of individuals to change behavior and also can increase the ability of the individual in controlling the excitation in the undesirable conditions. This study aimed to determine the effect of anger management training program by nursing staff on violence rate against them. METHODS: This was a two-group, two phase, semi-experimental study. Sixty six qualified nurses employed in emergency unit of Al-Zahra Hospital were divided into test and control groups. In this study, the modified questionnaire of World Health Organization was used with adequate validity and reliability to measure the violence rate and anger control. Thereafter, the test group received anger management training for four 60-minute sessions. RESULTS: The results of the study showed that there was no significant difference between the two groups in terms of demographic characteristics except marital status. In addition, there was a significant difference between the two groups in frequency distribution of psychological violence against nurses after the intervention, but there was no significant difference between the two groups in frequency distribution of physical violence against nurses. CONCLUSIONS: The results of this study corroborated the findings of the previous studies. Therefore, increase in self-control and communication skills and problem solving skills at the time of dealing with the patients and their relatives is a step in reducing one of the factors of violence at workplace. PMID- 22069409 TI - Investigating the therapeutic effect of vaginal cream containing garlic and thyme compared to clotrimazole cream for the treatment of mycotic vaginitis. AB - BACKGROUND: Vaginitis is the most prevalent gynecological problem for which women look for treatment and is responsible for 10 million physician visits annually. Use of herbal treatments has been recorded in many of patient groups as well as in general populations to increase health level. The present study was conducted with the purpose of determination and comparison of the effect of vaginal cream containing garlic and thyme compared to clotrimazole cream for the treatment of mycotic vaginitis. METHODS: This clinical trial is a prospective, multivariate, single-blind, two-stage, two-group study with randomized assignment of samples into the two groups. From the clinics in Isfahan in 2010, 64 cases (32 individuals in each group) entered the study. Data collection was accomplished by demographic information questionnaire and clinical performance checklist, and data analysis was performed by SPSS 16.0 software. RESULTS: Abundance distributions of clinical symptoms (vaginal discharge; vulval erythema and edema), patients' complaints (secretions, itching, dyspareunia, painful urination, and vaginal irritation) and clinical symptoms (existence of germinating hypha, acidity under 4.5, and culture of vaginal secretions) were different in each group prior to and after the intervention; these factors however were not different between the two groups before and after the intervention. CONCLUSIONS: The vaginal cream containing garlic and thyme is effective as much as clotrimazole vaginal cream for the treatment of candida vaginitis and there is no difference between responses to treatment by these two drugs. PMID- 22069410 TI - Experiences of university faculty members regarding communication in work environment. AB - BACKGROUND: Individuals have different understandings, beliefs, values and attitudes, and follow their own specific approach to express their feelings. The present research was aimed to study the experiences of the faculty members of nursing and midwifery department regarding communication in work environment. METHODS: As the phenomenon to be studied in the current research is the human experiences, the study was accomplished in nursing and midwifery department of seven universities, including Isfahan, Shahid Beheshti, Tehran, Iran, Mashhad, Shiraz, and Tabriz universities of medical sciences. The most common data collection technique in qualitative studies is the participants' observations, interview, and their written texts. In the present study, Collaizzi's seven steps were applied. RESULTS: We interviewed 36 individuals, including 20 women and 16 men. The intra-organizational communications influence the physical and mental health as well as performance of staffs in their work environment. CONCLUSIONS: This study expressed in the themes formulated from statements of the units under study. PMID- 22069411 TI - The process of confrontation with disability in patients with spinal cord injury. AB - BACKGROUND: Spinal injury can establish severe psychological outcomes for the patient and his/her family which requires high adjustment. Health system staff would be able to play their roles well in caring these patients provided with knowing what steps spinal injured people should pass to handle their disability and also what assistance they need in what stages from what sources. This study aimed to explain the process of confrontation with disability in spinal cord injured patients. METHODS: This was a qualitative study with grounded theory approach which was performed in Strauss and Corbin proposed method on twenty people with spinal cord injury who had past at least three months from their spinal injury. Sampling was done in purposive and theoretical method, and analysis of the results was also performed during constant comparative process. RESULTS: Central concept in the data was support which was associated with other concepts and affected them. The patients, with the help of internal and external support could overcome their main problem that was disability feeling and dependency on others and find a new definition for the self, and ultimately achieve the sense of independence and autonomy. CONCLUSIONS: Knowing the process of confrontation with disability along with better understanding of spinal cord injured people would help health system staff to actualize and support their potentials much better through strengthening internal resources and providing appropriate supportive services of each individual. PMID- 22069412 TI - A comparative study on attitude of contraceptive methods users towards common contraceptive methods. AB - BACKGROUND: Family planning is a method of thinking and a life style which is chosen voluntarily and according to the attitudes and responsible determination of the couples in order to promote the hygiene and convenience of the family. This study aimed to identify and compare the attitudes of the users of common contraceptive methods with regard to each method separately. METHODS: The descriptive study was conducted in 2010. The study samples included 378 women using common contraceptive methods as LD pills, IUD (intrauterine devices), condom, withdrawal, tubectomy (females sterilization) and vasectomy as well as withdrawal method. The samples were selected through systemic random sampling from 9 health care centers. The data collection tool was a researcher-made. In order to determine the validity and reliability of the questionnaires, the content validity and Cronbach's alpha correlation coefficient methods were used. In order to analyze the data, the descriptive and inferential statistical methods (ANOVA) were used. RESULTS: Mean score of attitude regarding different contraceptive methods in the group who were users of the same method was above the users of all the methods; however, total attitude score toward the contraceptive methods was approximately similar to each other in all the groups and there was no significant difference among the different groups. CONCLUSIONS: The findings of this study showed that attitude is an important factor in choosing the contraceptive methods; therefore, this issue should to be taken into account by the family planning planners and consultants. PMID- 22069413 TI - Comparing the effects of reflexology methods and Ibuprofen administration on dysmenorrhea in female students of Isfahan University of Medical Sciences. AB - BACKGROUND: Dysmenorrhea or menstrual pain is one of the most common disorders experienced by 50% of women in their reproductive age. Adverse effects of medical treatments and its failure rate of 20-25% have caused many women to seek other complementary and alternative treatment methods for primary dysmenorrhea. Hence, this study aimed to compare and determine the efficacy of reflexology and Ibuprofen on reduction of pain intensity and duration of menstrual pain. METHODS: This was a quasi-experimental clinical trial study on 68 students with primary dysmenorrhea living in Isfahan University of Medical Sciences' dormitories. Simple random sampling was done considering the inclusion criteria and then the students were randomly divided into two groups. In the reflexology group, the subjects received 10 reflexology sessions (40 minutes each) in two consecutive mense cycles. The Ibuprofen group received Ibuprofen (400 mg), once every eight hours for 3 days during 3 consecutive mense cycles. To assess the severity of dysmenorrhea, Standard McGill Pain Questionnaire, visual analog scale (VAS) and pain rating index (PRI) were used in this study. RESULTS: Findings of the study showed that the two groups had no statistically significant difference in terms of demographic characteristics (p > 0.05). Reflexology method was associated with more reduction of intensity and duration of menstrual pain in comparison with Ibuprofen therapy. Independent and Paired t-test showed that there was a significant difference in the two groups between intensity and duration of menstrual pain using VAS and PRI in each of the 3 cycles between reflexology and Ibuprofen groups (p < 0.05). CONCLUSIONS: Considering the results of the study, reflexology was superior to Ibuprofen on reducing dysmenorrhea and its treatment effect continued even after discontinuing the intervention in the third cycle. Therefore, considering that reflexology is a non-invasive, easy and cheap technique, it seems that it can replace anti-inflammatory drugs (NSAIDs) to avoid their adverse side effects. PMID- 22069414 TI - Reviewing time intervals from onset of the symptoms to thrombolytic therapy in patients with ST segment elevation myocardial infarction (STEMI). AB - BACKGROUND: Coronary artery diseases are one of the causes of early death all over the world. In developed countries, ischemic heart disease is responsible for half of the entire mortalities; however in developing countries it is estimated that from 9 million deaths per year, 32 percent are due to coronary artery disease. Acute coronary syndromes are responsible for over 250,000 deaths per year caused by progressive atherosclerotic process which would lead to rupture of the atherosclerotic plaque and establishing thrombosis. This study aimed to determine time intervals between the onset of the heart attack symptoms to thrombolytic therapy in patients with ST segment elevation myocardial infarction (STEMI) in selected hospitals of Isfahan University of Medical Sciences. METHODS: In this study, 180 subjects with first time STEMI were enrolled by categorized random sampling in cardiac care units of four hospitals affiliated to Isfahan University of Medical Sciences during 9 months. Necessary information were collected by asking the patients and reviewing their records. The data included demographic, prehospital and in-hospital data of the patients. RESULTS: The mean duration of time interval from the onset of heart attack symptoms to the first action in order to seek medical care was 01:16'(01:36') (h:m [SD]), from the symptoms onset to admission in emergency unit was 02:29'(02:00') and from admission in emergency unit to administration of thrombolytic drug was 01:04'(01:14'). CONCLUSIONS: Time interval between onset of the acute coronary symptoms and seek for medical care and arrival to the emergency unit in this study had a better condition than other studies, but the interval between the emergency admission and thrombolytic therapy was longer than other studies. PMID- 22069415 TI - The effect of education on behavioral intention model of mothers' attitude towards over weight preschool children's nutritional patterns. AB - BACKGROUND: Obesity and over weight is one of the causes of threatening children's present and future life. One of the factors that cause this problem is parents' attitude toward preschool children's nutritional patterns. Education can improve the parents' attitude and prevents from this big issue. This study aimed to assess changes in mother's attitude and behavioral intention using intention model. METHODS: This was a semi-experimental study with pre-test, post test design. Forty-five mothers with overweight preschool children attended this study. Sampling was based on cluster randomize sampling method. The researcher made questionnaire which was used in this study was standardized through content validity and test, re-test. RESULTS: Comparing the pretest and posttest scores indicated a statistically significant difference in the attitude mean score. The findings of this study suggest that attitude and behavioral intention about nutritional patterns can be improved through parents' education based on behavioral intention model such as attitude, subjective norm and behavioral intention. CONCLUSIONS: In order to have healthy children, parents should improve their knowledge about how they promote their attitude towards children's nutritional pattern. Therefore, new model of education can optimize correct healthy behavior. PMID- 22069416 TI - Effect of communication skill training using group psychoeducation method on the stress level of psychiatry ward nurses. AB - BACKGROUND: Nursing is a dynamic and supportive job, with the main role of taking care of patients. Maintaining appropriate communication of the nurse with the patients is particularly known as the main core of care in mental health. However, in spite of the importance of providing communication, one of the main sources of stress in nurses of psychiatry wards is communication with the patients. Some important reasons for inappropriate relationship between the nurse and patient can be lack of necessary skills to communicate with patients because of insufficient training. Although training communication skills is an important part of the education of medical and paramedical students, in recent studies it has been demonstrated that the communication skills learned in theoretical courses would not necessarily be transferred to clinical settings, and proving training in clinical settings is a must. The present study was carried out to determine the effect of training communication skills using psychoeducation method on the stress level of nurses of psychiatry wards in 2010. METHODS: This is a quasi-experimental study. The participants were 45 nurses; 23 and 22 in the experiment and control groups, respectively, working in psychiatry wards of Noor and Farabi hospitals, Isfahan, Iran. The sampling was carried out by the census method, and then the participants were randomly assigned to the two groups of experiment and control, using random number table. The two groups filled out the demographic data form and also the questionnaire on nurses' occupational stress, designed by the researcher. The questionnaire was filled out three times; before, immediately after, and one month after the training. Training of communication skills was carried out using group psychoeducation method, in six sessions, each lasted for 1.5 hours. The training sessions of the experiment group were held in Farabi Hospital. RESULTS: The findings indicated that before the intervention, the members of the two groups had a high level of occupational stress. Immediately after the training, the stress level of the experiment group decreased significantly, and the decrease was sustained for the following one month. CONCLUSIONS: Training communicative skills using group psychoeducation method can decrease the occupational stress of psychiatry ward nurses. PMID- 22069417 TI - Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome. AB - BACKGROUND: Since premenstrual syndrome (PMS) can cause suicide, dissociation of familial relationships, abnormalities in the daily work and inter-personal relationships in the patients, and bring about direct and indirect economic burden for the society, it is important to resolve the problems of the patients. The objective of the current study is to determine the effect of magnesium (Mg), combination of vitamin B6 and Mg, and the placebo on the severity of PMS in the patients affected by the disease referred to the health centers of Isfahan University of Medical Sciences during 2009-2010. METHODS: The participants were randomly assigned to two intervention groups and one control group. The study was carried out for four months in ten selected health centers in Isfahan. To confirm the PMS diagnosis in patients, they were asked to fill out the PMS daily symptom record form for two months and then, when the diagnosis was confirmed, the participants were randomly assigned to one of the three groups of the study (Mg, Mg plus vitamin B6, and placebo). Medical intervention was carried out in two menstrual cycles and the results of pre- and post-test were compared. RESULTS: After the intervention, the mean score of PMS significantly decreased in all the three groups (p < 0.05). The decrease was the greatest in the Mg plus vitamin B6 group, and was the least in the placebo group. CONCLUSIONS: The findings indicated that Mg plus vitamin B6 and placebo has the greatest and the least effect on the mean score of PMS, respectively. PMID- 22069418 TI - Pediatric neurosurgery - Indian prospective. PMID- 22069419 TI - Surgical management of Pott's disease of the spine in pediatric patients: A single surgeon's experience of 8 years in a tertiary care center. AB - STUDY DESIGN: A retrospective, case study of 64 pediatric patients who underwent spinal surgery for Pott's spine and have minimum 6 months follow-up. OBJECTIVE: The aim of this study was to evaluate the surgical management and outcome of 64 pediatric Pott's spine cases operated by single surgeon over last 8 years, with a minimum follow-up of 6 months. The prognostic significance and the outcome of the demographic factors, location of the disease, and its surgical approach were also evaluated in these patients. MATERIALS AND METHODS: The data collected retrospectively from the institute's record case sheets of the 64 pediatric patients with Pott's disease of the spine, operated between 2002 and 2010 in the Department of Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, were analyzed. The study population consisted of 40 male and 24 female pediatric patients. Clinical findings included back pain, paraparesis, kyphosis, fever, sensory disturbance, and bowel and bladder dysfunction. RESULTS: The most common region of Pott's disease was the thoracic region [21/64 (33%)] followed by craniovertebral junction (CVJ) [17/64 (27%)]. At presentation, all of the patients had neurological features of spinal cord compression. All patients were treated with antituberculous chemotherapy which was continued after the surgical intervention also. Transthoracic surgical approach [18/64 (28%)] was the most frequently required surgery followed by transoral decompression with posterior fusion [12/64 (19%)] depending on the site of disease and compression of neuraxis. Initially, more than two-third of the patients were in poor grade of Kumar and Kalra scoring as well as modified Kumar and Kalra scoring, which were reduced to about one fifth after the surgical intervention, and the outcome was good as the condition of 46 patients (72%) improved significantly. CONCLUSION: Currently, treatment of spinal tubercular infections requires a multidisciplinary team that includes infectious diseases experts, neuroradiologists, and spine surgeons. The key to successful management is early detection and timely and judicious surgical intervention, the decision of which needs to be taken in view of clinicoradiological compression of the spinal cord and nerve roots, age of the patient and responsiveness of ATT. PMID- 22069420 TI - Pediatric aneurysms and vein of Galen malformations. AB - Pediatric aneurysms are different from adult aneurysms - they are more rare, are giant and in the posterior circulation more frequently than in adults and may be associated with congenital disorders. Infectious and traumatic aneursyms are also seen more frequently. Vein of Galen malformations are even rarer entities. They may be of choroidal or mural type. Based on the degree of AV shunting they may present with failure to thrive, with hydrocephalus or in severe cases with heart failure. The only possible treatment is by endovascular techniques - both transarterial and transvenous routes are employed. Rarely transtorcular approach is needed. These cases should be managed by an experienced neurointerventionist. PMID- 22069421 TI - Hydrocephalus Indian scenario - A review. AB - Hydrocephalus is a common clinical problem seen in pediatric neurosurgical practice. Hydrocephalus involves dilatation of the cerebral ventricular system with corresponding, compressive effects on the parenchyma. It can be communicative or obstructive types. Congenital, acquired, infective, and secondary hydrocephalus have different clinical features with different modality of treatments. Ventriculoperitoneal shunt is the gold standard of treatment. Endoscopic 3(rd) ventriculostomy is rapidly gaining prominence as an alternative. Various kinds of hydrocephalus, their pathophysiology, treatment and complications are reviewed. PMID- 22069422 TI - Outcome of selective motor fasciculotomy in the treatment of upper limb spasticity. AB - OBJECTIVE: The objective was to assess the outcome of selective motor fasciculotomy in relieving upper limb harmful resistant spasticity and thereby to improve motor functions in persons with cerebral palsy. MATERIALS AND METHODS: Twenty people having cerebral palsy (12 females and 8 males) with age ranging from 5 to 35 (mean 12.85) years with upper limb resistant spasticity due to spastic hemiplegia (n=7), triplegia (n=6), and quadriplegia (n=7) were assessed using Modified Ashworth Scale, Selective Voluntary Control Grade, Wee FIM Scale and hand function evaluation. Selective motor fasciculotomy was performed on the musculocutaneous nerve (n=13) for elbow flexors spasticity, median nerve (n=24) for pronators and radial wrist flexors spasticity and ulnar nerve (n=3) for ulnar wrist flexors spasticity. Pre- and post-op therapeutic exercises were performed. RESULTS: Statistical analysis using the Wilcoxon Signed Ranks test showed significant reduction in spasticity and improvement in selective voluntary control, hand functions (grasp to hold a 2 inch rod), and Wee FIM (self-care domain in particular). There was no recurrence in spasticity and complications following surgery. CONCLUSIONS: The selective motor fasciculotomy of musculocutaneous, median, and ulnar nerves significantly reduces spasticity in the affected muscle groups and thereby improves the self-care (motor) functions in selected people with cerebral palsy who have harmful resistant spasticity without any organic shortening of the muscles. The procedure is safe and the spasticity does not recur. PMID- 22069423 TI - Pediatric epilepsy: The Indian experience. AB - Epilepsy is a common clinical entity in neurology clinics. The understanding of the genetics of epilepsy has undergone a sea change prompting re-classification by the International league against epilepsy recently. The prevalence rates of epilepsy in India are similar to those of developed nations. However, the large treatment gap is a major challenge to our public health system. Perinatal injuries are a major causative factor in pediatric group. We have discussed a few common etiologies such as neurocysticercosis and newer genetic epilepsy syndromes. We have also briefly touched upon the Indian experience in pediatric epilepsy surgery. PMID- 22069424 TI - Epilepsy surgery in India. AB - Modern epilepsy started in India in 1995 at Sri Chitra Tirunal Institute of Medical Science and Technology, Trivandrum and at All India Institute of Medical Sciences, New Delhi. At both centres the attempt was to get the program going with patients having surgically remediable epilepsy syndromes -who could be evaluated with non invasive investigations. The mainstay of the evaluation was a good quality epilepsy specific MRI and video EEG coupled with a SPECT study and a neuropsychological evaluation. Concordance of the focus on all investigations was critical to a good outcome. There were several problems on the way - but they were managed keeping in consideration our local needs and requirements. Intraoperative electocorticography was done and good outcomes attained. The critical determinants of success were the formation of a team with various interdisciplinary specialists and a strong will to succeed. PMID- 22069425 TI - Journal of pediatric neurosciences: 2006-2010. PMID- 22069426 TI - Craniostenosis. AB - Craniostenosis is a common problem in the pediatric neurosurgery departments. The management of this problem is still evolving. Some misconceptions exist regarding this condition particularly regarding the indications for surgery. The author started performing this surgery nearly two decades ago. The experience gained over time as well as the problems encountered are discussed. PMID- 22069427 TI - Anterior encephalocele - AIIMS experience a series of 133 patients. AB - BACKGROUND: Anterior encephaloceles are rare conditions. Except for a few places from South East Asia, no large series has been published in the World literature. MATERIALS AND METHODS: At AIIMS, we have managed 133 cases over a 40-year-period from 1971 to 2010. Frontoethmoidal type was the most frequent, noticed in 104 patients, followed by nasopharyngeal nasal in 12 and orbital encephaloceles in 6 patients. OBSERVATION: Ten patients were adults over the age of 18 years and 15 patients were between 5 and 18 years of age. Swelling over the nose was reported in all 104 patients with frontoethmoid type. In nasopharyngeal type, patients presented with respiratory problem. Patients with orbital mass had proptosis, on the side of encephalocele. Computed tomography (CT)/Magnetic resonance imaging (MRI) was performed in 127 patients, which was able to delineate the bone defect and associated brain anomalies. All the patients were subjected to repair of encephalocele. Patients with hypertelorism required orbital osteotomies and correction of deformity. OUTCOME: There were four deaths, all prior to 2000. No death was encountered in the last 10 years. CSF leak was the commonest postoperative complication, noticed in 24 patients. Overall cosmetic outcome was good. PMID- 22069429 TI - Development of pediatric neurosurgery in India. AB - The development of pediatric neurosurgery in this country actually began with holding of the 17(th) Annual Conference of the International Society for Pediatric Neurosurgery (ISPN) in 1989 in Mumbai. It subsequently led to the formation in 1990 of the Indian Society for Pediatric Neurosurgery (IndSPN), which is responsible for organizing regular annual conferences and CMEs in cooperation with the ISPN. The first three international CME programs were arranged in 1992, 1994 and 1995, followed by the next three courses from 1998 to 2000. Subsequently, five more such programs were organized in 2002, 2004, 2007, 2009, and 2010. The official publication, Journal of Pediatric Neurosciences (JPN), which was started in 2006, has also made good progress in the last 5 years. In the last 20 years, the IndSPN has made striking progress in the development and growth of pediatric neurosurgery in the country and has successfully managed to bring this subspeciality to an international level. The IndSPN now has about 150 active members and quite a few of them practice mainly pediatric neurosurgery. In large teaching institutions, pediatric neurosurgery has been accepted as a subspeciality with a designated neurosurgeon taking care of the pediatric patients. This augers well for the subspeciality as persons with greater interest and expertise will be tackling its problems. Some of these institutions have recently started or are in the process of starting the 1-year fellowship training program in pediatric neurosurgery. PMID- 22069428 TI - Spinal dysraphism. AB - To review the clinical features and current understanding of spina bifida with an emphasis on the Indian Scenario. Selected articles and current English language texts were reviewed. The authors experience was also reviewed and analysed. Spina bifida is a common congenital anomaly encompassing a wide spectrum of neural tube defects.It is broadly classified as spina bifida aperta and occulta. With the prenatal screening, the incidence of aperta is gradually declining, whereas the detection of occulta has increased with the advent of magnetic resonance imaging. Over the years, the understanding of pathophysiology has made a significant changein the management of these anomalies. Early detection and complete correction can significantly reduce the neurological disability. This article is an overview of spina bifida with a special emphasis on Indian scenario. PMID- 22069430 TI - Split cord malformation - A study of 300 cases at AIIMS 1990-2006. AB - BACKGROUND: Split cord malformation (SCM) is a rare condition. With decreasing incidence of neural tube defect (NTD) in the West, the reports of SCM are getting lesser and lesser. However, in India, spinal dysraphism is still a major problem encountered by the neurosurgeons. OBJECTIVE: Our aim was to analyze 300 patients of SCM for their clinical features, radiological findings and outcome of surgery, which can throw light on the subject to others, who have less scope of finding these cases frequently. MATERIALS AND METHODS: Over a 16-year period, we encountered 300 cases of SCM at AIIMS. Over the same period, more than 1500 cases of NTD were managed. SCM was noticed in 20% of cases with NTD. Skin stigmata were noted in two-third of the cases, and scoliosis and foot deformity were observed in 50% and 48% cases, respectively. Motor and sensory deficits were observed in 80% and 70% cases, respectively. Commonest site affected was lumbar or dorsolumbar (55% and 23%, respectively). In 3% cases, it was cervical in location. Magnetic resonance imaging (MRI) scan revealed a large number of anomalies like lipoma, neuroenteric cyst, thick filum and dermoid or epidermoid cysts. All the patients were surgically treated. In type I, bony spurs were excised, and in type II, bands tethering the cord were released. Associated anomalies were managed in the same sitting. Patients were followed up from 3 months to 3 years. RESULTS: Overall improvement was noticed in 50% and stabilization in 44% cases and deterioration of neurological status was recorded in 6% cases. However, 50% of those who deteriorated improved to preop status prior to discharge, 7-10 days following surgery. CONCLUSIONS: SCM is rare and not many large series are available. We operated 300 cases and noticed a large number of associated anomalies and also multilevel and multisite splits. Improvement or stabilization was noted in 94% and deterioration in 6% cases. We recommended prophylactic surgery for our asymptomatic patients. PMID- 22069431 TI - Pediatric suprasellar lesions. AB - Pediatric brain tumors have always been challenging as well as intriguing in their anatomical, surgical, and postsurgical management-related issues. They are a heterogeneous set of pathologies involving different age groups in childhood and also differ widely from their adult counterparts as far as adjuvant therapies are concerned. Though neurosurgeons across the world are radical in surgery for most of the pediatric tumors, it can often be at the cost of future quality of life in suprasellar tumors. As the time has gone by, the pendulum has swung toward rather conservative and maximal safe surgical resections with adjuvant therapies coming to the forefront. Hence, the aim is to achieve a good quality of life for these children along with a control of tumor growth (rather than cure) and to again tackle the tumors, if required, once these children reach adolescence or adulthood. We have reviewed the literature for different pediatric suprasellar tumors and discussed their current management giving our perspective with illustrative cases. PMID- 22069432 TI - Tumors of the posterior third ventricular region in pediatric patients: The Indian perspective and a review of literature. AB - BACKGROUND: Diverse tumors in the posterior third ventricular region (TPTVR) frequently occur in children. A decade's experience with pediatric TPTVR is presented, focusing on the Indian perspective. MATERIALS AND METHODS: 25 children (age range: 3-18 years; mean age: 13.32 years; presentation range: 7 days-2.5 years) had clinico-radiological assessment with contrast computed tomography (CT) and magnetic resonance imaging (MRI). The ventricular/lumbar cerebrospinal fluid (CSF) alpha feto protein (AFP)/beta human chorionic gonadotrophin (HCG) estimation was done when radiological suspicion of a germ cell tumor was present. Extent of resection was deemed partial when some tumor mass remained at the end of surgery, near total when <10% was retained over vital neurovascular structures, and total when complete resection was attained. RESULTS: Operations included infratentorial supracerebellar approach (n = 12), occipito transtentorial approach (n = 2), endoscopic biopsy and third ventriculostomy (n = 1), frontal parasagittal craniotomy, interhemispheric transcallosal subchoroidal approach (n = 2), middle temporal gyrus transcortical transventricular approach (n = 1), fronto-temporo-zygomatic combined transylvian and subtemporal approach (n = 1) and right ventriculoperitoneal shunt and stereotactic biopsy (n = 1). Only CSF diversion was performed for five patients with a small TPTVR. CSF diversion was required in 12 (48%) patients. Tumor pathology included pinealoblastoma (n = 4; one with pineocytic differentiation), nongerminomatous germ cell tumor (NGGCT; n = 3), germinoma (n = 3), pilocytic astrocytoma (n = 2), epidermoid (n = 3) and primitive neuroectodermal tumor (PNET), fibrillary astrocytoma, glioblastoma, teratoma, and meningioma (n = 1, respectively). A patient with neurocysticercosis was diagnosed solely on MRI (four did not undergo biopsy). Fractionated radiotherapy was administered in 13 patients with primary pineal tumors, PNET, NGGCT, fibrillary astrocytoma and glioblastoma. Extent of excision was total in 10 (40%), near total in 5 (20%), partial in 3 (12%) and a biopsy in 2 (8%) patients. CONCLUSIONS: Histopathologic characterization of TPTVR is essential prior to their further management. Benign lesions often have a good prognosis following gross total surgical resection. Pure germinomas are highly susceptible to radiotherapy. NGGCTs often have malignant components that require adjuvant therapy following surgery. The advancements in microsurgical techniques have led to gratifying perioperative results in these deep-seated lesions. PMID- 22069433 TI - Management of posterior fossa gliomas in children. AB - Brain tumours form the most common type of solid tumour in children and more that 50% of these are infratentorial. Cerebellar astrocytomas and brain stem gliomas are the commonest posterior fossa glial tumours in children. Cerebellar astrocytomas represent up to 10% of all primary brain tumours and up to 25% of posterior fossa tumors in children, with Low grade gliomas forming the commonest of the cerebellar gliomas. They commonly present with symptoms and signs of raised intracranial pressure due to obstructive hydrocephalus. Radiologically they may be solid or cystic with or without a mural nodule. Surgical excision is the mainstay of treatment and forms the most consistent factor influencing progression free and long term survival. While majority of the tumours are pilocytic astrocytomas, they may also be fibrillary astrocytomas or even high grade tumours. Tumour histology does not appear to be an independent factor in the prognosis of these children, and therefore no palliative treatment after surgery is advocated. Brain stem gliomas account for approximately 10% of all pediatric brain tumours. Cranial nerve signs, ataxia and cerebellar signs with or without symptoms and signs of raised intracranial pressure are classically described symptoms and signs. Radiographic findings and clinical correlates can be used to categorize brain stem tumours into four types: diffuse, focal, exophytic and cervicomedullary. Histologically most brain stem gliomas are fibrillary astrocytomas. Diffuse brain stem gliomas are the most commonly seen tumour in the brain stem. These lesions are malignant high grade fibrillary astrocytomas. Focal tumours of the brain stem are demarcated lesions generally less than 2 cms in size, without associated edema. Most commonly seen in the midbrain or medulla, they form a heterogeneous pathological group, showing indolent growth except when the lesion is a PNET. Dorsally exophytic tumours lie in the fourth ventricle, while cervicomedullary lesions are similar to spinal intramedullary tumours. Expanding lesions are the only lesions amenable for excision while infiltrative and ventral lesions are not. PMID- 22069435 TI - Intramedullary tumors in children. AB - Intramedullary tumors of the spinal cord account for 35-40% of intraspinal tumors in children. The biological behavior of these tumors is of slow progression, and hence aggressive surgery has been advocated. Surgical adjuncts include use of intraoperative neurophysiological monitoring, preoperative ultrasound, microsurgical techniques and ultrasonic suction devices. Osteoplastic laminoplasty approaches avoid post-laminectomy deformities in younger children. Postoperative radiotherapy and more recently chemotherapy regimes have been proposed for incompletely resected tumors. PMID- 22069434 TI - Medulloblastoma in childhood-King Edward Memorial hospital surgical experience and review: Comparative analysis of the case series of 365 patients. AB - AIM: Medulloblastoma is one of the most common posterior fossa tumors in childhood. The treatment-related side effects as well as predictive outcome still remain as a major challenge. The improved understanding of the disease and advances in molecular biology is changing the treatment paradigms from Chang's staging system to molecular risk stratification. However, surgery still remains as an important mainstay of therapy and is formidable. The role of radical surgery has always been a crucial factor in the outcome of these patients, the best survival being reported in patients who had total excision of the tumor and with no metastasis. PATIENT AND METHODS: An analysis of 365 patients (age<18 years) of medulloblastoma who underwent treatment at the Seth G.S. Medical College and King Edward VII Memorial hospital (KEM), Mumbai over a 25- year period (1985-2000 and 2001-2010) is presented. The clinical profile, radiological features, pathology and surgical nuances are discussed. RESULTS: The most common age group affected was between 3 and 12 years. 75.3% presented with headaches, vomiting and 63.2% with papilledema. Sitting position was used in majority of cases. A total of 8 patients underwent shunting; all of them were in the postoperative period (5.19%). 92.2% (142 cases) had classical medulloblastoma, 5.1% (8 cases) had desmoplastic variant, 1.9% (3 cases) had anaplastic changes and 0.6% (1 case) had glial differentiation. The 5-year and 10-year progression free survival rate was 73 and 41% for average risk disease while for high risk disease rate it was 34%. The mortality rate was 2%. The quality of life was enhanced in patients who survived 5-10 years after treatment. CONCLUSION: Surgery for medulloblastoma is formidable. The option of sitting position for medulloblastoma surgery is still viable. A vigilant neuroanesthesiologist and a safe surgery are necessary to achieve a good postoperative result. Radiological characteristics are helpful adjuncts for determining effective surgical strategy. Permanent CSF drainage can be avoided in majority of patients and can be definitively considered in progressive symptomatic hydrocephalus. A safe maximal resection and a good Karnofsky score are paramount to ensure compliance with adjuvant therapy and contribute to an overall survival advantage. PMID- 22069436 TI - Pediatric bony craniovertebral junction abnormalities: Institutional experience of 10 years. AB - OBJECTIVE: To study the clinical features and treatment outcome of pediatric patients with bony craniovertebral abnormalities. MATERIALS AND METHODS: The authors studied 189 consecutive cases of pediatric bony craniovertebral junction abnormalities operated between 2001 and March, 2010. RESULTS: The pathologies were developmental (n = 162), traumatic (n = 18) and tuberculous (n = 9). Surgical procedures included transoral decompression (n = 118), occipitocervical fusion (OCF, n = 139), C 1 -C 2 fusion (n = 45), and posterior fossa decompression (n = 5). Methods for OCF included contoured stainless steel rods (n = 86), titanium lateral mass screws and plates (n = 47) and steel wires (n = 6). Constructs of all patients of posterior fixation with contoured rods and wires or lateral mass screw and rod who could be followed up were either stable/fused or were fused and stable. No implant failure was noticed among these two surgical procedures. However, 6 patients with C 1-C 2 fusion had broken wires on follow-up requiring repeat posterior fixation. Good neurological outcome was observed even in poor-grade patients. No significant effect on the curvature or growth of the spine was observed at follow-up. CONCLUSIONS: Pediatric craniovertebral junction anomalies can be managed successfully with good outcomes using a low cost contoured rod and wires. PMID- 22069437 TI - Brain tuberculomas, tubercular meningitis, and post-tubercular hydrocephalus in children. AB - Central nervous system tuberculosis in children presents commonly as tubercular meningitis, post-tubercular meningitis hydrocephalus, and much more rarely as space-occupying lesions known as tuberculomas. The occurrence of this condition, though previously reported only in the developing world, is now frequently reported in human immunodeficiency virus positive migrants in the western world. The exact pathogenesis of this condition is still incompletely understood, and the mainstay of treatment is chemotherapeutic regimes. Neurosurgical intervention is rarely necessary, and is confined to cases of hydrocephalus after tubercular meningitis and to large tubeculomas with space-occupying effects. PMID- 22069438 TI - Lexical knowledge without a lexicon? AB - Although for many years a sharp distinction has been made in language research between rules and words - with primary interest on rules - this distinction is now blurred in many theories. If anything, the focus of attention has shifted in recent years in favor of words. Results from many different areas of language research suggest that the lexicon is representationally rich, that it is the source of much productive behavior, and that lexically specific information plays a critical and early role in the interpretation of grammatical structure. But how much information can or should be placed in the lexicon? This is the question I address here. I review a set of studies whose results indicate that event knowledge plays a significant role in early stages of sentence processing and structural analysis. This poses a conundrum for traditional views of the lexicon. Either the lexicon must be expanded to include factors that do not plausibly seem to belong there; or else virtually all information about word meaning is removed, leaving the lexicon impoverished. I suggest a third alternative, which provides a way to account for lexical knowledge without a mental lexicon. PMID- 22069444 TI - Efficiency of peptide nucleic acid-directed PCR clamping and its application in the investigation of natural diets of the Japanese eel leptocephali. AB - Polymerase chain reaction (PCR)-clamping using blocking primer and DNA-analogs, such as peptide nucleotide acid (PNA), may be used to selectively amplify target DNA for molecular diet analysis. We investigated PCR-clamping efficiency by studying PNA position and mismatch with complementary DNA by designing PNAs at five different positions on the nuclear rDNA internal transcribed spacer 1 of the Japanese eel Anguilla japonica in association with intra-specific nucleotide substitutions. All five PNAs were observed to efficiently inhibit amplification of a fully complementary DNA template. One mismatch between PNA and template DNA inhibited amplification of the template DNA, while two or more mismatches did not. DNA samples extracted from dorsal muscle and intestine of eight wild-caught leptochephalus larvae were subjected to this analysis, followed by cloning, nucleotide sequence analysis, and database homology search. Among 12 sequence types obtained from the intestine sample, six were identified as fungi. No sequence similarities were found in the database for the remaining six types, which were not related to one another. These results, in conjunction with our laboratory observations on larval feeding, suggest that eel leptocephali may not be dependent upon living plankton for their food source. PMID- 22069443 TI - Putting into practice domain-linear motif interaction predictions for exploration of protein networks. AB - PDZ domains recognise short sequence motifs at the extreme C-termini of proteins. A model based on microarray data has been recently published for predicting the binding preferences of PDZ domains to five residue long C-terminal sequences. Here we investigated the potential of this predictor for discovering novel protein interactions that involve PDZ domains. When tested on real negative data assembled from published literature, the predictor displayed a high false positive rate (FPR). We predicted and experimentally validated interactions between four PDZ domains derived from the human proteins MAGI1 and SCRIB and 19 peptides derived from human and viral C-termini of proteins. Measured binding intensities did not correlate with prediction scores, and the high FPR of the predictor was confirmed. Results indicate that limitations of the predictor may arise from an incomplete model definition and improper training of the model. Taking into account these limitations, we identified several novel putative interactions between PDZ domains of MAGI1 and SCRIB and the C-termini of the proteins FZD4, ARHGAP6, NET1, TANC1, GLUT7, MARCH3, MAS, ABC1, DLL1, TMEM215 and CYSLTR2. These proteins are localised to the membrane or suggested to act close to it and are often involved in G protein signalling. Furthermore, we showed that, while extension of minimal interacting domains or peptides toward tandem constructs or longer peptides never suppressed their ability to interact, the measured affinities and inferred specificity patterns often changed significantly. This suggests that if protein fragments interact, the full length proteins are also likely to interact, albeit possibly with altered affinities and specificities. Therefore, predictors dealing with protein fragments are promising tools for discovering protein interaction networks but their application to predict binding preferences within networks may be limited. PMID- 22069445 TI - Reduction of plasma gelsolin levels correlates with development of multiple organ dysfunction syndrome and fatal outcome in burn patients. AB - BACKGROUND: Depletion of the circulating actin-binding protein, plasma gelsolin (pGSN) has been described in critically ill surgical patients. We hypothesized that the extent of pGSN reduction might correlate with different outcome of burn patients. The study was performed to evaluate the prognostic implications of pGSN levels on the development of multiple organ dysfunction syndrome (MODS) and fatal outcome in a group of severely burn patients. METHODS AND FINDINGS: 95 patients were included, and they were divided into three groups with different burn area: group I (n = 33), group II (n = 32) and group III (n = 30). According to whether there was development of MODS or not, patients were divided into MODS group (n = 28) and none-MODS group (n = 67); then the patients with MODS were further divided into non-survivor group (n = 17) and survivor group (n = 11). The peripheral blood samples were collected on postburn days (PBD) 1, 3, 7, 14, and 21. The levels of pGSN were determined and T cells were procured from the blood. The contents of cytokines (IL-2, IL-4 and IFN-gamma) released by T cells were also measured. The related factors of prognosis were analyzed by using multivariate logistic regression analysis. The results showed that pGSN concentrations, as well as the levels of IL-2 and IFN-gamma, decreased markedly on PBD 1-21, whereas, the levels of IL-4 increased markedly in all burn groups as compared with normal controls (P<0.05 or P<0.01), and there were obviously differences between group I and group III (P<0.05 or P<0.01). The similar results were found in MODS patients and the non-survivor group as compared with those without MODS and the survival group on days 3-21 postburn (P<0.05 or P<0.01). Moreover, as the pGSN levels decreased, the incidence of septic complication as well as MODS remarkably increased. CONCLUSIONS: pGSN levels appear to be an early prognostic marker in patients suffering from major burns. PMID- 22069446 TI - Bayesian analysis of high-throughput quantitative measurement of protein-DNA interactions. AB - Transcriptional regulation depends upon the binding of transcription factor (TF) proteins to DNA in a sequence-dependent manner. Although many experimental methods address the interaction between DNA and proteins, they generally do not comprehensively and accurately assess the full binding repertoire (the complete set of sequences that might be bound with at least moderate strength). Here, we develop and evaluate through simulation an experimental approach that allows simultaneous high-throughput quantitative analysis of TF binding affinity to thousands of potential DNA ligands. Tens of thousands of putative binding targets can be mixed with a TF, and both the pre-bound and bound target pools sequenced. A hierarchical Bayesian Markov chain Monte Carlo approach determines posterior estimates for the dissociation constants, sequence-specific binding energies, and free TF concentrations. A unique feature of our approach is that dissociation constants are jointly estimated from their inferred degree of binding and from a model of binding energetics, depending on how many sequence reads are available and the explanatory power of the energy model. Careful experimental design is necessary to obtain accurate results over a wide range of dissociation constants. This approach, which we call Simultaneous Ultra high-throughput Ligand Dissociation EXperiment (SULDEX), is theoretically capable of rapid and accurate elucidation of an entire TF-binding repertoire. PMID- 22069447 TI - An evaluation of different target enrichment methods in pooled sequencing designs for complex disease association studies. AB - Pooled sequencing can be a cost-effective approach to disease variant discovery, but its applicability in association studies remains unclear. We compare sequence enrichment methods coupled to next-generation sequencing in non-indexed pools of 1, 2, 10, 20 and 50 individuals and assess their ability to discover variants and to estimate their allele frequencies. We find that pooled resequencing is most usefully applied as a variant discovery tool due to limitations in estimating allele frequency with high enough accuracy for association studies, and that in solution hybrid-capture performs best among the enrichment methods examined regardless of pool size. PMID- 22069448 TI - A peptide of SPARC interferes with the interaction between caspase8 and Bcl2 to resensitize chemoresistant tumors and enhance their regression in vivo. AB - SPARC, a matricellular protein with tumor suppressor properties in certain human cancers, was initially identified in a genome-wide analysis of differentially expressed genes in chemotherapy resistance. Its exciting new role as a potential chemosensitizer arises from its ability to augment the apoptotic cascade, although the exact mechanisms are unclear. This study further examines the mechanism by which SPARC may be promoting apoptosis and identifies a smaller peptide analogue with greater chemosensitizing and tumor-regressing properties than the native protein. We examined the possibility that the apoptosis-enhancing activity of SPARC could reside within one of its three biological domains (N terminus (NT), the follistatin-like (FS), or extracellular (EC) domains), and identified the N-terminus as the region with its chemosensitizing properties. These results were not only confirmed by studies utilizing stable cell lines overexpressing the different domains of SPARC, but as well, with a synthetic 51 aa peptide spanning the NT-domain. It revealed that the NT-domain induced a significantly greater reduction in cell viability than SPARC, and that it enhanced the apoptotic cascade via its activation of caspase 8. Moreover, in chemotherapy resistant human colon, breast and pancreatic cancer cells, its chemosensitizing properties also depended on its ability to dissociate Bcl2 from caspase 8. These observations translated to clinically significant findings in that, in-vivo, mouse tumor xenografts overexpressing the NT-domain of SPARC had significantly greater sensitivity to chemotherapy and tumor regression, even when compared to the highly-sensitive SPARC-overexpressing tumors. Our results identified an interplay between the NT-domain, Bcl2 and caspase 8 that helps augment apoptosis and as a consequence, a tumor's response to therapy. This NT domain of SPARC and its 51-aa peptide are highly efficacious in modulating and enhancing apoptosis, thereby conferring greater chemosensitivity to resistant tumors. Our findings provide additional insight into mechanisms involved in chemotherapy resistance and a potential novel therapeutic that specifically targets this devastating phenomenon. PMID- 22069449 TI - Pattern of amino acid substitutions in transmembrane domains of beta-barrel membrane proteins for detecting remote homologs in bacteria and mitochondria. AB - beta-barrel membrane proteins play an important role in controlling the exchange and transport of ions and organic molecules across bacterial and mitochondrial outer membranes. They are also major regulators of apoptosis and are important determinants of bacterial virulence. In contrast to beta-helical membrane proteins, their evolutionary pattern of residue substitutions has not been quantified, and there are no scoring matrices appropriate for their detection through sequence alignment. Using a Bayesian Monte Carlo estimator, we have calculated the instantaneous substitution rates of transmembrane domains of bacterial beta-barrel membrane proteins. The scoring matrices constructed from the estimated rates, called bbTM for beta-barrel Transmembrane Matrices, improve significantly the sensitivity in detecting homologs of beta-barrel membrane proteins, while avoiding erroneous selection of both soluble proteins and other membrane proteins of similar composition. The estimated evolutionary patterns are general and can detect beta-barrel membrane proteins very remote from those used for substitution rate estimation. Furthermore, despite the separation of 2-3 billion years since the proto-mitochondrion entered the proto-eukaryotic cell, mitochondria outer membrane proteins in eukaryotes can also be detected accurately using these scoring matrices derived from bacteria. This is consistent with the suggestion that there is no eukaryote-specific signals for translocation. With these matrices, remote homologs of beta-barrel membrane proteins with known structures can be reliably detected at genome scale, allowing construction of high quality structural models of their transmembrane domains, at the rate of 131 structures per template protein. The scoring matrices will be useful for identification, classification, and functional inference of membrane proteins from genome and metagenome sequencing projects. The estimated substitution pattern will also help to identify key elements important for the structural and functional integrity of beta-barrel membrane proteins, and will aid in the design of mutagenesis studies. PMID- 22069450 TI - Oral vaccination of baculovirus-expressed VP28 displays enhanced protection against White Spot Syndrome Virus in Penaeus monodon. AB - White Spot Syndrome Virus (WSSV) is an infectious pathogen of shrimp and other crustaceans, and neither effective vaccines nor adequate treatments are currently available. WSSV is an enveloped dsDNA virus, and one of its major envelope proteins, VP28, plays a pivotal role in WSSV infection. In an attempt to develop a vaccine against WSSV, we inserted the VP28 gene into a baculovirus vector tailored to express VP28 on the baculovirus surface under the WSSV ie1 promoter (Bac-VP28). The Bac-VP28 incorporated abundant quantity (65.3 ug/ml) of VP28. Shrimp were treated by oral and immersion vaccination with either Bac-VP28 or wild-type baculovirus (Bac-wt). The treatment was followed by challenge with WSSV after 3 and 15 days. Bac-VP28 vaccinated shrimp showed significantly higher survival rates (oral: 81.7% and 76.7%; immersion: 75% and 68.4%) than Bac-wt or non-treated shrimp (100% mortality). To verify the protective effects of Bac VP28, we examined in vivo expression of VP28 by immunohistochemistry and quantified the WSSV copy number by qPCR. In addition to that, we quantified the expression levels shrimp genes LGBP and STAT by real-time RT-PCR from the samples obtained from Bac-VP28 vaccinated shrimp at different duration of vaccine regime. Our findings indicate that oral vaccination of shrimp with Bac-VP28 is an attractive preventative measure against WSSV infection that can be used in the field. PMID- 22069451 TI - Lack of adherence to isoniazid chemoprophylaxis in children in contact with adults with tuberculosis in Southern Ethiopia. AB - SETTING: Hawassa, Southern Region of Ethiopia. OBJECTIVES: To determine compliance to isoniazid (INH) preventive therapy (IPT) and its effectiveness in preventing (TB) disease in children in contact with adults with pulmonary TB (PTB). DESIGN: This was a prospective cohort study of children <15 years old in contact with adults with smear-positive PTB. Asymptomatic children <=5 years were provided IPT independently of their Tuberculin Skin Test (TST) status and children >5 years old were given advice but did not receive IPT, as recommended by the National TB control programme. Compliance to IPT and incidence of clinical TB were determined monthly for six months and then quarterly for up to 30 months. RESULTS: One hundred and eighty four children in contact with 83 smear-positive PTB cases were identified. Eighty two were <=5 and 102>5 years old. Only 27 (33%) of 82 children given IPT took it for >4 months and 10 (12%) completed the 6-month course. The main reason for non-compliance was the perception that drugs were not necessary when the child was healthy. Eleven children (all except one >5 years old) developed symptoms of TB disease and initiated treatment, resulting in an incidence of 28.6 cases for all and 53.5 for children >5 years old per 1000 children-year. CONCLUSION: Compliance to IPT in children is poor in Southern Region of Ethiopia and this was associated with the parents' perception of the low importance of chemoprophylaxis in asymptomatic children. Poor compliance might be an important barrier for the wider implementation of IPT. TRIAL REGISTRATION: Clinicaltrials.gov NCT00456469. PMID- 22069452 TI - Bilateral fronto-parietal integrity in young chronic cigarette smokers: a diffusion tensor imaging study. AB - BACKGROUND: Cigarette smoking continues to be the leading cause of preventable morbidity and mortality in China and other countries. Previous studies have demonstrated gray matter loss in chronic smokers. However, only a few studies assessed the changes of white matter integrity in this group. Based on those previous reports of alterations in white matter integrity in smokers, the aim of this study was to examine the alteration of white matter integrity in a large, well-matched sample of chronic smokers and non-smokers. METHODOLOGY/PRINCIPAL FINDINGS: Using in vivo diffusion tensor imaging (DTI) to measure the differences of whole-brain white matter integrity between 44 chronic smoking subjects (mean age, 28.0+/-5.6 years) and 44 healthy age- and sex-matched comparison non-smoking volunteers (mean age, 26.3+/-5.8 years). DTI was performed on a 3-Tesla Siemens scanner (Allegra; Siemens Medical System). The data revealed that smokers had higher fractional anisotropy (FA) than healthy non-smokers in almost symmetrically bilateral fronto-parietal tracts consisting of a major white matter pathway, the superior longitudinal fasciculus (SLF). CONCLUSION/SIGNIFICANCE: We found the almost symmetrically bilateral fronto-parietal whiter matter changes in a relatively large sample of chronic smokers. These findings support the hypothesis that chronic cigarette smoking involves alterations of bilateral fronto-parietal connectivity. PMID- 22069453 TI - The birth-death-mutation process: a new paradigm for fat tailed distributions. AB - Fat tailed statistics and power-laws are ubiquitous in many complex systems. Usually the appearance of of a few anomalously successful individuals (bio species, investors, websites) is interpreted as reflecting some inherent "quality" (fitness, talent, giftedness) as in Darwin's theory of natural selection. Here we adopt the opposite, "neutral", outlook, suggesting that the main factor explaining success is merely luck. The statistics emerging from the neutral birth-death-mutation (BDM) process is shown to fit marvelously many empirical distributions. While previous neutral theories have focused on the power-law tail, our theory economically and accurately explains the entire distribution. We thus suggest the BDM distribution as a standard neutral model: effects of fitness and selection are to be identified by substantial deviations from it. PMID- 22069454 TI - Factors associated with elevated ALT in an international HIV/HBV co-infected cohort on long-term HAART. AB - BACKGROUND: Previous studies have demonstrated that hepatitis B virus (HBV) infection increases the risk for ALT elevations in HIV-HBV co-infected patients during the first year of HAART; however, there is limited data on the prevalence of ALT elevations with prolonged HAART in this patient group. METHODS/PRINCIPAL FINDINGS: To identify factors associated with ALT elevations in an HIV-HBV co infected cohort receiving prolonged HAART, data from 143 co-infected patients on HAART enrolled in an international HIV-HBV co-infected cohort where ALT measurements were obtained every 6 months was analysed. A person-visit analysis was used to determine frequency of ALT elevation (>= 2.5*ULN) at each visit. Factors associated with ALT elevation were determined using multivariate logistic regression with generalized estimating equations to account for correlated data. The median time on HAART at the end of follow-up was 5.6 years (range 0.4-13.3) years. During follow-up, median ALT was 36 U/L with 10.6% of person-visits classified as having ALT elevation. Most ALT elevations were grade 2 (86.5%), with only 13.5% of all ALT elevations grade 3 or higher. Univariate associations with ALT elevation (p<0.05) included history of AIDS, HBV DNA >= 2,000 IU/ml, HBeAg positive, study visit CD4 <200 cells/ml and nadir CD4 <200 cells/ml. In the multivariate analysis, only study visit CD4 <200 cells/ml (OR 2.07, 95%CI 1.04 4.11, p = 0.04) and HBeAg positive status (OR 2.22, 95%CI 1.03-4.79, p = 0.04) were independently associated with ALT elevation. CONCLUSIONS: In this HIV-HBV co infected cohort, elevated ALT after >1 year of HAART was uncommon, and severe ALT elevations were rare. HIV-HBV co-infected patients on long-term HAART who are either HBeAg positive or have a CD4 count of <200 cells/ml are at increased risk for ALT elevations. PMID- 22069455 TI - Distribution of extracellular glutamate in the neuropil of hippocampus. AB - Reported values of extracellular glutamate concentrations in the resting state depend on the method of measurement and vary ~1000-fold. As glutamate levels in the micromolar range can cause receptor desensitization and excitotoxicity, and thus affect neuronal excitability, an accurate determination of ambient glutamate is important. Part of the variability of previous measurements may have resulted from the sampling of glutamate in different extracellular compartments, e.g., synaptic versus extrasynaptic volumes. A steep concentration gradient of glutamate between these two compartments could be maintained, for example, by high densities of glutamate transporters arrayed at the edges of synapses. We have used two photon laser scanning microscopy and electrophysiology to investigate whether extracellular glutamate is compartmentalized in acute hippocampal slices. Pharmacological blockade of NMDARs had no effect on Ca(2+) transients generated in dendritic shafts or spines of CA1 pyramidal neurons by depolarization, suggesting that ambient glutamate is too low to activate a significant number of NMDARs. Furthermore, blockade of transporters did not flood the synapse with glutamate, indicating that synaptic NMDARs are not protected from high concentrations of extrasynaptic glutamate. We suggest that, in the CA1 region of hippocampus, glutamate transporters do not create a privileged space within the synapse but rather keep ambient glutamate at very low levels throughout the neuropil. PMID- 22069456 TI - When tuberculosis comes back: who develops recurrent tuberculosis in california? AB - BACKGROUND: Recurrent tuberculosis suggests potentially modifiable gaps in tuberculosis treatment and control activities. The frequency of late recurrences following treatment completion has not been well-studied. We determined the frequency of, and risk factors associated with, tuberculosis that recurs at least one year after completion of anti-tuberculosis therapy in California. METHODS: The study population included culture-positive, pulmonary tuberculosis patients reported to the California tuberculosis case registry from 1993 to 2007 who completed anti-tuberculosis therapy. A person with late recurrent tuberculosis was defined as an individual that appeared in the registry more than once, determined by match on name and date-of-birth, with at least one year between treatment completion of the first episode and treatment initiation of the second episode. RESULTS: Among 23,517 tuberculosis patients, 148 (0.63%) had a late recurrence. Independent risk factors for recurrence included: infection with a pyrazinamide mono-resistant isolate (adjusted hazard ratio, 2.93; p = 0.019); initiation of an isoniazid- and rifampin-only treatment regimen (adjusted hazard ratio, 2.55; p = 0.0412); sputum smear-positive disease (adjusted hazard ratio, 1.96; p = 0.0003); human immunodeficiency virus infection (adjusted hazard ratio, 1.81; p = 0.0149); and birth in the United States (adjusted hazard ratio, 1.88; p = 0.0002). Infection with an isoniazid mono-resistant isolate was protective (adjusted hazard ratio, 0.25; p = 0.0171). CONCLUSIONS: The low frequency of late recurrent tuberculosis in California suggests that local TB control programs are largely successful at preventing this adverse outcome. Nonetheless, we identified subpopulations at increased risk of late tuberculosis recurrence that may benefit from additional medical or public health interventions. PMID- 22069457 TI - Genetic linkage map of a high yielding FELDA deli*yangambi oil palm cross. AB - Enroute to mapping QTLs for yield components in oil palm, we constructed the linkage map of a FELDA high yielding oil palm (Elaeis guineensis), hybrid cross. The parents of the mapping population are a Deli dura and a pisifera of Yangambi origin. The cross out-yielded the average by 8-21% in four trials all of which yielded comparably to the best current commercial planting materials. The higher yield derived from a higher fruit oil content. SSR markers in the public domain - from CIRAD and MPOB, as well as some developed in FELDA - were used for the mapping, augmented by locally-designed AFLP markers. The female parent linkage map comprised 317 marker loci and the male parent map 331 loci, both in 16 linkage groups each. The number of markers per group ranged from 8-47 in the former and 12-40 in the latter. The integrated map was 2,247.5 cM long and included 479 markers and 168 anchor points. The number of markers per linkage group was 15-57, the average being 29, and the average map density 4.7 cM. The linkage groups ranged in length from 77.5 cM to 223.7 cM, with an average of 137 cM. The map is currently being validated against a closely related population and also being expanded to include yield related QTLs. PMID- 22069458 TI - Circuit specific functions of cannabinoid CB1 receptor in the balance of investigatory drive and exploration. AB - Well balanced novelty seeking and exploration are fundamental behaviours for survival and are found to be dysfunctional in several psychiatric disorders. Recent studies suggest that the endocannabinoid (eCB) system is an important control system for investigatory drive. Pharmacological treatment of rodents with cannabinergic drugs results in altered social and object investigation. Interestingly, contradictory results have been obtained, depending on the treatment, drug concentration and experimental conditions. The cannabinoid type 1 (CB1) receptor, a central component of the eCB system, is predominantly found at the synapses of two opposing neuronal populations, i.e. on inhibitory GABAergic and excitatory glutamatergic neurons. In the present study, using different transgenic mouse lines, we aimed at investigating the impact of CB1 receptor inactivation in glutamatergic or GABAergic neurons on investigatory behaviour. We evaluated animate (interaction partner) and inanimate (object) exploratory behaviour in three different paradigms. We show that exploration was increased when CB1 receptor was deleted from cortical and striatal GABAergic neurons. No effect was observed when CB1 receptor was deleted specifically from dopamine receptor D1-expressing striatal GABAergic medium spiny neurons. In contrast, deletion of CB1 receptor from cortical glutamatergic neurons resulted in a decreased exploration. Thus, our results indicate that exploratory behaviour is accurately balanced in both, the social and non-social context, by the eCB system via CB1 receptor activation on cortical glutamatergic and GABAergic neurons. In addition, the results could explain the contradictory findings of previous pharmacological studies and could further suggest a possibility to readjust an imbalance in exploratory behaviour observed in psychiatric disorders. PMID- 22069459 TI - Adhesive F-actin waves: a novel integrin-mediated adhesion complex coupled to ventral actin polymerization. AB - At the leading lamellipodium of migrating cells, protrusion of an Arp2/3 nucleated actin network is coupled to formation of integrin-based adhesions, suggesting that Arp2/3-mediated actin polymerization and integrin-dependent adhesion may be mechanistically linked. Arp2/3 also mediates actin polymerization in structures distinct from the lamellipodium, in "ventral F-actin waves" that propagate as spots and wavefronts along the ventral plasma membrane. Here we show that integrins engage the extracellular matrix downstream of ventral F-actin waves in several mammalian cell lines as well as in primary mouse embryonic fibroblasts. These "adhesive F-actin waves" require a cycle of integrin engagement and disengagement to the extracellular matrix for their formation and propagation, and exhibit morphometry and a hierarchical assembly and disassembly mechanism distinct from other integrin-containing structures. After Arp2/3 mediated actin polymerization, zyxin and VASP are co-recruited to adhesive F actin waves, followed by paxillin and vinculin, and finally talin and integrin. Adhesive F-actin waves thus represent a previously uncharacterized integrin-based adhesion complex associated with Arp2/3-mediated actin polymerization. PMID- 22069460 TI - Development of an RNA interference tool, characterization of its target, and an ecological test of caste differentiation in the eusocial wasp polistes. AB - Recent advancements in genomics provide new tools for evolutionary ecological research. The paper wasp genus Polistes is a model for social insect evolution and behavioral ecology. We developed RNA interference (RNAi)-mediated gene silencing to explore proposed connections between expression of hexameric storage proteins and worker vs. gyne (potential future foundress) castes in naturally founded colonies of P. metricus. We extended four fragments of putative hexamerin encoding P. metricus transcripts acquired from a previous study and fully sequenced a gene that encodes Hexamerin 2, one of two proposed hexameric storage proteins of P. metricus. MALDI-TOF/TOF, LC-MSMS, deglycosylation, and detection of phosphorylation assays showed that the two putative hexamerins diverge in peptide sequence and biochemistry. We targeted the hexamerin 2 gene in 5(th) (last)-instar larvae by feeding RNAi-inducing double-stranded hexamerin 2 RNA directly to larvae in naturally-founded colonies in the field. Larval development and adult traits were not significantly altered in hexamerin 2 knockdowns, but there were suggestive trends toward increased developmental time and less developed ovaries, which are gyne characteristics. By demonstrating how data acquisition from 454/Roche pyrosequencing can be combined with biochemical and proteomics assays and how RNAi can be deployed successfully in field experiments on Polistes, our results pave the way for functional genomic research that can contribute significantly to learning the interactions of environment, development, and the roles they play in paper wasp evolution and behavioral ecology. PMID- 22069461 TI - Video game playing is independently associated with blood pressure and lipids in overweight and obese adolescents. AB - OBJECTIVE: To examine the association between duration and type of screen time (TV, video games, computer time) and blood pressure (BP) and lipids in overweight and obese adolescents. DESIGN: This is a cross-sectional study of 282 overweight or obese adolescents aged 14-18 years (86 males, 196 females) assessed at baseline prior to beginning a lifestyle intervention study for weight control. Sedentary behaviours, defined as hours per day spent watching TV, playing video games, recreational computer use and total screen time were measured by self report. We examined the associations between sedentary behaviours and BP and lipids using multiple linear regression. RESULTS: Seated video gaming was the only sedentary behaviour associated with elevated BP and lipids before and after adjustment for age, sex, pubertal stage, parental education, body mass index (BMI), caloric intake, percent intake in dietary fat, physical activity (PA) duration, and PA intensity. Specifically, video gaming remained positively associated with systolic BP (adjusted r = 0.13, beta = 1.1, p<0.05) and total cholesterol/HDL ratio (adjusted r = 0.12, beta = 0.14, p<0.05). CONCLUSIONS: Playing video games was the only form of sedentary behaviour that was independently associated with increased BP and lipids. Our findings provide support for reducing time spent playing seated video games as a possible means to promote health and prevent the incidence of cardiovascular disease (CVD) risk factors in this high risk group of overweight and obese adolescents. Future research is needed to first replicate these findings and subsequently aim to elucidate the mechanisms linking seated video gaming and elevated BP and lipids in this high risk population. TRIAL REGISTRATION: Clinicaltrials.gov NCT00195858. PMID- 22069462 TI - Analogous mechanisms of resistance to benzothiazinones and dinitrobenzamides in Mycobacterium smegmatis. AB - Tuberculosis is still a leading cause of death worldwide. The selection and spread of Mycobacterium tuberculosis multidrug-resistant (MDR-TB) and extensively drug-resistant strains (XDR-TB) is a severe public health problem. Recently, two different classes of chemical series, the benzothiazinones (BTZ) and the dinitrobenzamide (DNB) derivatives have been found to be highly active against M. tuberculosis, including XDR-TB strains. The target of BTZs is DprE1 protein which works in concert with DprE2 to form the heteromeric decaprenylphosphoryl-beta-D ribose 2'-epimerase, involved in Decaprenyl-Phospho-Arabinose (DPA) biosynthesis. Interestingly, it has been shown that the DNBs block the same pathway thus suggesting that both drugs could share the same target. Moreover, in Mycobacterium smegmatis the overexpression of the NfnB nitroreductase led to the inactivation of the BTZs by reduction of a critical nitro-group to an amino group. In this work several spontaneous M. smegmatis mutants resistant to DNBs were isolated. Sixteen mutants, showing high levels of DNB resistance, exhibited a mutation in the Cys394 of DprE1. Using fluorescence titration and mass spectrometry it has been possible to monitor the binding between DprE1 and DNBs, achieving direct evidence that MSMEG_6382 is the cellular target of DNBs in mycobacteria. Additionally, M. smegmatis mutants having low levels of resistance to DNBs harbor various mutations in MSMEG_6503 gene encoding the transcriptional repressor of the nitroreductase NfnB. By LC/MS analysis it has been demonstrated that NfnB is responsible for DNB inactivation. Taken together, our data demonstrate that both DNB and BTZ drugs share common resistance mechanisms in M. smegmatis. PMID- 22069463 TI - APOE genotype and cardio-respiratory fitness interact to determine adiposity in 8 year-old children from the Tasmanian Infant Health Survey. AB - APOE plays a well established role in lipid metabolism. Animal model evidence suggests APOE may also be associated with adiposity, but this has not been thoroughly investigated in humans. We measured adiposity (BMI, truncal fat mass, waist circumference), physical activity (PA), cardiorespiratory fitness and APOE genotype (E2, E3, E4) in 292 8-year-old children from the Tasmanian Infant Health Survey (TIHS), an Australian population-based prospective birth cohort. Our aims were to examine the association of APOE with child adiposity, and to examine the interplay between this association and other measured factors. We found that APOE was associated with child lipid profiles. APOE was also associated with child adiposity measures. The association was E4 allele-specific, with adiposity lower in the E4-containing group (BMI: Mean difference -0.90 kg/m2; 95% confidence intervals (CI) -1.51, -0.28; p = 0.004). The association of APOE4 with lower BMI differed by fitness status (difference in effect p = 0.002), and was more evident among the less fit (mean difference -1.78 kg/m2; 95% CI -2.74, -0.83; p<0.001). Additionally, associations between BMI and lipids were only apparent in those of lower fitness who did not carry APOE4. Similar overall findings were observed when truncal fat mass and waist circumference were used as alternative adiposity measures. APOE4 and cardiorespitatory fitness could interact to influence child adiposity. In studies addressing the genetic determinants of childhood obesity, the context of child fitness should also be taken into account. PMID- 22069464 TI - Hypotheses of spatial stock structure in orange roughy Hoplostethus atlanticus inferred from diet, feeding, condition, and reproductive activity. AB - We evaluate hypotheses for meso-scale spatial structure in an orange roughy (Hoplostethus atlanticus) stock using samples collected during research trawl surveys off the east coast of New Zealand. Distance-based linear models and generalised additive models were used to identify the most significant biological, environmental, and temporal predictors of variability in diet, proportion of stomachs containing prey, standardised weight of prey, fish somatic weight, fish total weight, and reproductive activity. The diet was similar to that observed elsewhere, and varied with ontogeny, depth, and surface water temperature. Smaller sized and female orange roughy in warmer bottom water were most likely to contain food. Fish condition and reproductive activity were highest at distances more than 20 km from the summit of the hills. Trawl survey catches indicated greater orange roughy densities in hill strata, suggesting hill habitat was favoured. However, analyses of feeding, condition, and reproductive activity indicated hill fish were not superior, despite fish densities on hills being reduced by fishing which, in principle, should have reduced intra-specific competition for food and other resources. Hypotheses for this result include: (1) fish in relatively poor condition visit hills to feed and regain condition and then leave, or (2) commercial fishing has disturbed feeding aggregations and/or caused habitat damage, making fished hills less productive. Mature orange roughy were observed on both flat and hill habitat during periods outside of spawning, and if this spatial structure was persistent then a proportion of the total spawning stock biomass would remain unavailable to fisheries targeting hills. Orange roughy stock assessments informed only by data from hills may well be misleading. PMID- 22069465 TI - Segtor: rapid annotation of genomic coordinates and single nucleotide variations using segment trees. AB - Various research projects often involve determining the relative position of genomic coordinates, intervals, single nucleotide variations (SNVs), insertions, deletions and translocations with respect to genes and their potential impact on protein translation. Due to the tremendous increase in throughput brought by the use of next-generation sequencing, investigators are routinely faced with the need to annotate very large datasets. We present Segtor, a tool to annotate large sets of genomic coordinates, intervals, SNVs, indels and translocations. Our tool uses segment trees built using the start and end coordinates of the genomic features the user wishes to use instead of storing them in a database management system. The software also produces annotation statistics to allow users to visualize how many coordinates were found within various portions of genes. Our system currently can be made to work with any species available on the UCSC Genome Browser. Segtor is a suitable tool for groups, especially those with limited access to programmers or with interest to analyze large amounts of individual genomes, who wish to determine the relative position of very large sets of mapped reads and subsequently annotate observed mutations between the reads and the reference. Segtor (http://lbbc.inca.gov.br/segtor/) is an open source tool that can be freely downloaded for non-profit use. We also provide a web interface for testing purposes. PMID- 22069466 TI - An inducible cell-cell fusion system with integrated ability to measure the efficiency and specificity of HIV-1 entry inhibitors. AB - HIV-1 envelope glycoproteins (Envs) mediate virus entry by fusing the viral and target cell membranes, a multi-step process that represents an attractive target for inhibition. Entry inhibitors with broad-range activity against diverse isolates of HIV-1 may be extremely useful as lead compounds for the development of therapies or prophylactic microbicides. To facilitate the identification of such inhibitors, we have constructed a cell-cell fusion system capable of simultaneously monitoring inhibition efficiency and specificity. In this system, effector cells stably express a tetracycline-controlled transactivator (tTA) that enables tightly inducible expression of both HIV-1 Env and the Renilla luciferase (R-Luc) reporter protein. Target cells express the HIV-1 receptors, CD4 and CCR5, and carry the firefly luciferase (F-Luc) reporter gene under the control of a tTA responsive promoter. Thus, Env-mediated fusion of these two cell types allows the tTA to diffuse to the target cell and activate the expression of the F-Luc protein. The efficiency with which an inhibitor blocks cell-cell fusion is measured by a decrease in the F-Luc activity, while the specificity of the inhibitor is evaluated by its effect on the R-Luc activity. The system exhibited a high dynamic range and high Z'-factor values. The assay was validated with a reference panel of inhibitors that target different steps in HIV-1 entry, yielding inhibitory concentrations comparable to published virus inhibition data. Our system is suitable for large-scale screening of chemical libraries and can also be used for detailed characterization of inhibitory and cytotoxic properties of known entry inhibitors. PMID- 22069467 TI - Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas. AB - We undertook this study to understand how the transcription factor Sox2 contributes to the malignant phenotype of glioblastoma multiforme (GBM), the most aggressive primary brain tumor. We initially looked for unbalanced genomic rearrangements in the Sox2 locus in 42 GBM samples and found that Sox2 was amplified in 11.5% and overexpressed in all the samples. These results prompted us to further investigate the mechanisms involved in Sox2 overexpression in GBM. We analyzed the methylation status of the Sox2 promoter because high CpG density promoters are associated with key developmental genes. The Sox2 promoter presented a CpG island that was hypomethylated in all the patient samples when compared to normal cell lines. Treatment of Sox2-negative glioma cell lines with 5-azacitidine resulted in the re-expression of Sox2 and in a change in the methylation status of the Sox2 promoter. We further confirmed these results by analyzing data from GBM cases generated by The Cancer Genome Atlas project. We observed Sox2 overexpression (86%; N = 414), Sox2 gene amplification (8.5%; N = 492), and Sox 2 promoter hypomethylation (100%; N = 258), suggesting the relevance of this factor in the malignant phenotype of GBMs. To further explore the role of Sox2, we performed in vitro analysis with brain tumor stem cells (BTSCs) and established glioma cell lines. Downmodulation of Sox2 in BTSCs resulted in the loss of their self-renewal properties. Surprisingly, ectopic expression of Sox2 in established glioma cells was not sufficient to support self renewal, suggesting that additional factors are required. Furthermore, we observed that ectopic Sox2 expression was sufficient to induce invasion and migration of glioma cells, and knockdown experiments demonstrated that Sox2 was essential for maintaining these properties. Altogether, our data underscore the importance of a pleiotropic role of Sox2 and suggest that it could be used as a therapeutic target in GBM. PMID- 22069468 TI - Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia. AB - Diabetic retinopathy (DR) is a common cause of blindness. Although many studies have indicated an association between homocysteine and DR, the results so far have been equivocal. Amongst the many determinants of homocysteine, B-vitamin status was shown to be a major confounding factor, yet very little is known about its relationship to DR. In the present study, we, therefore, investigated the status of B-vitamins and homocysteine in DR. A cross-sectional case-control study was conducted with 100 normal control (CN) subjects and 300 subjects with type-2 diabetes (T2D). Of the 300 subjects with T2D, 200 had retinopathy (DR) and 100 did not (DNR). After a complete ophthalmic examination including fundus fluorescein angiography, the clinical profile and the blood levels of all B vitamins and homocysteine were analyzed. While mean plasma homocysteine levels were found to be higher in T2D patients compared with CN subjects, homocysteine levels were particularly high in the DR group. There were no group differences in the blood levels of vitamins B1 and B2. Although the plasma vitamin-B6 and folic acid levels were significantly lower in the DNR and DR groups compared with the CN group, there were no significant differences between the diabetes groups. Interestingly, plasma vitamin-B12 levels were found to be significantly lower in the diabetes groups compared with the CN group; further, the levels were significantly lower in the DR group compared with the DNR group. Higher homocysteine levels were significantly associated with lower vitamin-B12 and folic acid but not with other B-vitamins. Additionally, hyperhomocysteinemia and vitamin-B12 deficiency did not seem to be related to subjects' age, body mass index, or duration of diabetes. These results thus suggest a possible association between vitamin-B12 deficiency and hyperhomocysteinemia in DR. Further, the data indicate that vitamin-B12 deficiency could be an independent risk factor for DR. PMID- 22069469 TI - Platelets retain high levels of active plasminogen activator inhibitor 1. AB - The vascular fibrinolytic system is crucial for spontaneous lysis of blood clots. Plasminogen activator inhibitor 1 (PAI-1), the principal inhibitor of the key fibrinolytic enzyme tissue-type plasminogen activator (tPA), is present in platelets at high concentrations. However, the majority of PAI-1 stored in platelets has been considered to be inactive. Our recent finding (Brogren H, et al. Blood 2004) that PAI-1 de novo synthesized in platelets remained active for over 24 h, suggested that PAI-1 stored in the alpha-granules might be active to a larger extent than previously reported. To re-evaluate this issue, we performed experiments where the fraction of active PAI-1 was estimated by analyzing the tPA PAI-1 complex formation. In these experiments platelets were lysed with Triton X 100 in the presence of serial dilutions of tPA and subsequently the tPA-PAI-1 complex was evaluated by Western blot. Also, using a non-immunologic assay, tPA was labeled with (125)I, and (125)I-tPA and (125)I-tPA-PAI-1 was quantified by scintigraphy. Interestingly, both methods demonstrated that the majority (>50%) of platelet PAI-1 is active. Further analyses suggested that pre-analytical procedures used in previous studies (sonication or freezing/thawing) may have substantially reduced the activity of platelet PAI-1, which has lead to an underestimation of the proportion of active PAI-1. Our in vitro results are more compatible with the role of PAI-1 in clot stabilization as demonstrated in physiological and pathophysiological studies. PMID- 22069470 TI - The molecular basis for the broad substrate specificity of human sulfotransferase 1A1. AB - Cytosolic sulfotransferases (SULTs) are mammalian enzymes that detoxify a wide variety of chemicals through the addition of a sulfate group. Despite extensive research, the molecular basis for the broad specificity of SULTs is still not understood. Here, structural, protein engineering and kinetic approaches were employed to obtain deep understanding of the molecular basis for the broad specificity, catalytic activity and substrate inhibition of SULT1A1. We have determined five new structures of SULT1A1 in complex with different acceptors, and utilized a directed evolution approach to generate SULT1A1 mutants with enhanced thermostability and increased catalytic activity. We found that active site plasticity enables binding of different acceptors and identified dramatic structural changes in the SULT1A1 active site leading to the binding of a second acceptor molecule in a conserved yet non-productive manner. Our combined approach highlights the dominant role of SULT1A1 structural flexibility in controlling the specificity and activity of this enzyme. PMID- 22069472 TI - Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV infected patients: a systematic review and meta-analysis. AB - BACKGROUND: Interferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear. METHODS: We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T SPOT) on blood for the diagnosis of active TB in HIV-infected patients. RESULTS: The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6-80.5%) and 77.4% (95%CI, 71.4 82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0-78.0%) and 63.1% (95%CI, 57.6-68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8 11.3%) and 13.2% (95%CI, 10.6-16.0%) for QFT-GIT and T-SPOT, respectively. CONCLUSION: IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy. PMID- 22069471 TI - Multiple doublesex-related genes specify critical cell fates in a C. elegans male neural circuit. AB - BACKGROUND: In most animal species, males and females exhibit differences in behavior and morphology that relate to their respective roles in reproduction. DM (Doublesex/MAB-3) domain transcription factors are phylogenetically conserved regulators of sexual development. They are thought to establish sexual traits by sex-specifically modifying the activity of general developmental programs. However, there are few examples where the details of these interactions are known, particularly in the nervous system. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that two C. elegans DM domain genes, dmd-3 and mab-23, regulate sensory and muscle cell development in a male neural circuit required for mating. Using genetic approaches, we show that in the circuit sensory neurons, dmd-3 and mab-23 establish the correct pattern of dopaminergic (DA) and cholinergic (ACh) fate. We find that the ETS-domain transcription factor gene ast 1, a non-sex-specific, phylogenetically conserved activator of dopamine biosynthesis gene transcription, is broadly expressed in the circuit sensory neuron population. However, dmd-3 and mab-23 repress its activity in most cells, promoting ACh fate instead. A subset of neurons, preferentially exposed to a TGF beta ligand, escape this repression because signal transduction pathway activity in these cells blocks dmd-3/mab-23 function, allowing DA fate to be established. Through optogenetic and pharmacological approaches, we show that the sensory and muscle cell characteristics controlled by dmd-3 and mab-23 are crucial for circuit function. CONCLUSIONS/SIGNIFICANCE: In the C. elegans male, DM domain genes dmd-3 and mab-23 regulate expression of cell sub-type characteristics that are critical for mating success. In particular, these factors limit the number of DA neurons in the male nervous system by sex-specifically regulating a phylogenetically conserved dopamine biosynthesis gene transcription factor. Homologous interactions between vertebrate counterparts could regulate sex differences in neuron sub-type populations in the brain. PMID- 22069473 TI - Complement and the alternative pathway play an important role in LPS/D-GalN induced fulminant hepatic failure. AB - Fulminant hepatic failure (FHF) is a clinically severe type of liver injury with an extremely high mortality rate. Although the pathological mechanisms of FHF are not well understood, evidence suggests that the complement system is involved in the pathogenesis of a variety of liver disorders. In the present study, to investigate the role of complement in FHF, we examined groups of mice following intraperitoneal injection of LPS/D-GalN: wild-type C57BL/6 mice, wild-type mice treated with a C3aR antagonist, C5aR monoclonal antibody (C5aRmAb) or CR2-Factor H (CR2-fH, an inhibitor of the alternative pathway), and C3 deficient mice (C3-/- mice). The animals were euthanized and samples analyzed at specific times after LPS/D-GalN injection. The results show that intraperitoneal administration of LPS/D-GalN activated the complement pathway, as evidenced by the hepatic deposition of C3 and C5b-9 and elevated serum levels of the complement activation product C3a, the level of which was associated with the severity of the liver damage. C3a receptor (C3aR) and C5a receptor (C5aR) expression was also upregulated. Compared with wild-type mice, C3-/- mice survived significantly longer and displayed reduced liver inflammation and attenuated pathological damage following LPS/D-GalN injection. Similar levels of protection were seen in mice treated with C3aR antagonist,C5aRmAb or CR2-fH. These data indicate an important role for the C3a and C5a generated by the alternative pathway in LPS/D GalN-induced FHF. The data further suggest that complement inhibition may be an effective strategy for the adjunctive treatment of fulminant hepatic failure. PMID- 22069474 TI - Pulmonary embolism incidence and fatality trends in chinese hospitals from 1997 to 2008: a multicenter registration study. AB - BACKGROUND: There has not been sufficient evidence to support the Asians being less susceptible to pulmonary embolism (PE) than other ethnicities, because the prevalence of PE/deep venous thrombosis (DVT) in different racial and ethnic groups has not been carefully studied until recently except in Caucasians. To test the hypothesis that the Chinese population has a lower risk for PE, this study comprehensively assessed the hospital-based incidence and case fatality rates for PE during the 1997-2008 in China. METHODS: A registration study of patients with suspected PE syndromes admitted to 60 level-3 hospitals involved in the National Cooperative Project for the Prevention and Treatment of Venous Thromboembolism (NCPPT) was conducted from January 1997 to December 2008. The only exclusion criterion was an age of less than 18 years. Helical computed tomography scan, ventilation-perfusion lung scintigraphy or pulmonary angiography was carried out before or after hospitalization. All images were reviewed and evaluated independently by two specialists. RESULTS: A total of 18,206 patients were confirmed with PE from 16,972,182 hospital admissions. The annual incidence was 0.1% (95% CI: 0.1% to 0.2%). The overall incidence of PE in male patients (0.2%, 95% CI: 0.1% to 0.3%) was higher than that in female patients (0.1% and 95% CI: 0.0% to 0.1%). An increasing incidence gradient for PE was noticed from Southern to Northern China. In addition, the case fatality rate was apparently decreasing: 25.1% (95% CI: 16.2% to 36.9%) in 1997 to 8.7% (95% CI: 3.5% to 15.8%) in 2008. CONCLUSIONS: Our findings suggest the relatively stable PE incidence and decreasing fatality trends in Chinese hospitals may be partially attributable to the implementation of the NCCPT and suggest the government should reevaluate the severity of PE so that health resources for the prevention, diagnosis and treatment of PE could be used to their fullest. PMID- 22069475 TI - Does speciation between Arabidopsis halleri and Arabidopsis lyrata coincide with major changes in a molecular target of adaptation? AB - Ever since Darwin proposed natural selection as the driving force for the origin of species, the role of adaptive processes in speciation has remained controversial. In particular, a largely unsolved issue is whether key divergent ecological adaptations are associated with speciation events or evolve secondarily within sister species after the split. The plant Arabidopsis halleri is one of the few species able to colonize soils highly enriched in zinc and cadmium. Recent advances in the molecular genetics of adaptation show that the physiology of this derived ecological trait involves copy number expansions of the AhHMA4 gene, for which orthologs are found in single copy in the closely related A. lyrata and the outgroup A. thaliana. To gain insight into the speciation process, we ask whether adaptive molecular changes at this candidate gene were contemporary with important stages of the speciation process. We first inferred the scenario and timescale of speciation by comparing patterns of variation across the genomic backgrounds of A. halleri and A. lyrata. Then, we estimated the timing of the first duplication of AhHMA4 in A. halleri. Our analysis suggests that the historical split between the two species closely coincides with major changes in this molecular target of adaptation in the A. halleri lineage. These results clearly indicate that these changes evolved in A. halleri well before industrial activities fostered the spread of Zn- and Cd polluted areas, and suggest that adaptive processes related to heavy-metal homeostasis played a major role in the speciation process. PMID- 22069476 TI - Fast and cost-effective mining of microsatellite markers using NGS technology: an example of a Korean water deer Hydropotes inermis argyropus. AB - BACKGROUND: Microsatellites, a special class of repetitive DNA sequence, have become one of the most popular genetic markers for population/conservation genetic studies. However, its application to endangered species has been impeded by high development costs, a lack of available sequences, and technical difficulties. The water deer Hydropotes inermis is the sole existing endangered species of the subfamily Capreolinae. Although population genetics studies are urgently required for conservation management, no species-specific microsatellite marker has been reported. METHODS: We adopted next-generation sequencing (NGS) to elucidate the microsatellite markers of Korean water deer and overcome these impediments on marker developments. We performed genotyping to determine the efficiency of this method as applied to population genetics. RESULTS: We obtained 98 Mbp of nucleotide information from 260,467 sequence reads. A total of 20,101 di-/tri-nucleotide repeat motifs were identified; di-repeats were 5.9-fold more common than tri-repeats. [CA](n) and [AAC](n)/[AAT](n) repeats were the most frequent di- and tri-repeats, respectively. Of the 17,206 di-repeats, 12,471 microsatellite primer pairs were derived. PCR amplification of 400 primer pairs yielded 106 amplicons and 79 polymorphic markers from 20 individual Korean water deer. Polymorphic rates of the 79 new microsatellites varied from 2 to 11 alleles per locus (H(e): 0.050-0.880; H(o): 0.000-1.000), while those of known microsatellite markers transferred from cattle to Chinese water deer ranged from 4 to 6 alleles per locus (H(e): 0.279-0.714; H(o): 0.300-0.400). CONCLUSIONS: Polymorphic microsatellite markers from Korean water deer were successfully identified using NGS without any prior sequence information and deposited into the public database. Thus, the methods described herein represent a rapid and low cost way to investigate the population genetics of endangered/non-model species. PMID- 22069477 TI - Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30698 patients. AB - BACKGROUND: Taxanes have been extensively used as adjuvant chemotherapy for the treatment of early or operable breast cancer, particularly in high risk, node negative breast cancer. Previous studies, however, have reported inconsistent findings regarding their clinical efficacy and safety. We investigated disease free survival (DFS), overall survival (OS), and drug-related toxicities of taxanes by a systematic review and meta-analysis. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched PubMed, EMBASE, the Cochrane Center Register of Controlled Trials, proceedings of major meetings, and reference lists of articles for studies conducted between January 1980 and April 2011. Randomized controlled trials (RCTs) comparing chemotherapy with and without taxanes in the treatment of patients with early-stage or operable breast cancer were eligible for inclusion in our analysis. The primary endpoint was DFS. Nineteen RCTs including 30698 patients were identified, including 8426 recurrence events and 3803 deaths. Taxanes administration yielded a 17% reduction of hazard ratio (HR) for DFS (HR = 0.83, 95% CI 0.79-0.88, p<0.001) and a 17% reduction of HR for OS (HR = 0.83, 95% CI 0.77-0.90, p<0.001). For high risk, node-negative breast cancer, the pooled HR also favoured the taxane-based treatment arm over the taxane-free treatment arm (HR = 0.82, 95% CI 0.77-0.87, p = 0.022). A significantly increased rate of neutropenia, febrile neutropenia, fatigue, diarrhea, stomatitis, and oedema was observed in the taxane-based treatment arm. CONCLUSIONS/SIGNIFICANCE: Adjuvant chemotherapy with taxanes could reduce the risk of cancer recurrence and death in patients with early or operable breast cancer, although the drug-related toxicities should be balanced. Furthermore, we also demonstrated that patients with high risk, node-negative breast cancer also benefited from taxanes therapy, a result that was not observed in previous studies. PMID- 22069478 TI - TOPAZ1, a novel germ cell-specific expressed gene conserved during evolution across vertebrates. AB - BACKGROUND: We had previously reported that the Suppression Subtractive Hybridization (SSH) approach was relevant for the isolation of new mammalian genes involved in oogenesis and early follicle development. Some of these transcripts might be potential new oocyte and granulosa cell markers. We have now characterized one of them, named TOPAZ1 for the Testis and Ovary-specific PAZ domain gene. PRINCIPAL FINDINGS: Sheep and mouse TOPAZ1 mRNA have 4,803 bp and 4,962 bp open reading frames (20 exons), respectively, and encode putative TOPAZ1 proteins containing 1,600 and 1653 amino acids. They possess PAZ and CCCH domains. In sheep, TOPAZ1 mRNA is preferentially expressed in females during fetal life with a peak during prophase I of meiosis, and in males during adulthood. In the mouse, Topaz1 is a germ cell-specific gene. TOPAZ1 protein is highly conserved in vertebrates and specifically expressed in mouse and sheep gonads. It is localized in the cytoplasm of germ cells from the sheep fetal ovary and mouse adult testis. CONCLUSIONS: We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line. PMID- 22069479 TI - Evaluation of the sublingual route for administration of influenza H5N1 virosomes in combination with the bacterial second messenger c-di-GMP. AB - Avian influenza A H5N1 is a virus with pandemic potential. Mucosal vaccines are attractive as they have the potential to block viruses at the site of entry, thereby preventing both disease and further transmission. The intranasal route is safe for the administration of seasonal live-attenuated influenza vaccines, but may be less suitable for administration of pandemic vaccines. Research into novel mucosal routes is therefore needed. In this study, a murine model was used to compare sublingual administration with intranasal and intramuscular administration of influenza H5N1 virosomes (2 ug haemagglutinin; HA) in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di GMP). We found that sublingual immunisation effectively induced local and systemic H5N1-specific humoral and cellular immune responses but that the magnitude of response was lower than after intranasal administration. However, both the mucosal routes were superior to intramuscular immunisation for induction of local humoral and systemic cellular immune responses including high frequencies of splenic H5N1-specific multifunctional (IL-2+TNF-alpha+) CD4+ T cells. The c-di-GMP adjuvanted vaccine elicited systemic haemagglutination inhibition (HI) antibody responses (geometric mean titres >= 40) both when administered sublingually, intranasally and inramuscularly. In addition, salivary HI antibodies were elicited by mucosal, but not intramuscular vaccination. We conclude that the sublingual route is an attractive alternative for administration of pandemic influenza vaccines. PMID- 22069480 TI - A suppressor/enhancer screen in Drosophila reveals a role for wnt-mediated lipid metabolism in primordial germ cell migration. AB - Wnt proteins comprise a large family of secreted ligands implicated in a wide variety of biological roles. WntD has previously been shown to inhibit the nuclear accumulation of Dorsal/NF-kappaB protein during embryonic dorsal/ventral patterning and the adult innate immune response, independent of the well-studied Armadillo/beta-catenin pathway. In this paper, we present a novel phenotype for WntD mutant embryos, suggesting that this gene is involved in migration of primordial germ cells (PGC) to the embryonic gonad. Additionally, we describe a genetic suppressor/enhancer screen aimed at identifying genes required for WntD signal transduction, based on the previous observation that maternal overexpression of WntD results in lethally dorsalized embryos. Using an algorithm to narrow down our hits from the screen, we found two novel WntD signaling components: Fz4, a member of the Frizzled family, and the Drosophila Ceramide Kinase homolog, Dcerk. We show here that Dcerk and Dmulk (Drosophila Multi substrate lipid kinase) redundantly mediate PGC migration. Our data are consistent with a model in which the activity of lipid phosphate phosphatases shapes a concentration gradient of ceramide-1-phosphate (C1P), the product of Dcerk, allowing proper PGC migration. PMID- 22069481 TI - The role of host traits, season and group size on parasite burdens in a cooperative mammal. AB - The distribution of parasites among hosts is often characterised by a high degree of heterogeneity with a small number of hosts harbouring the majority of parasites. Such patterns of aggregation have been linked to variation in host exposure and susceptibility as well as parasite traits and environmental factors. Host exposure and susceptibility may differ with sexes, reproductive effort and group size. Furthermore, environmental factors may affect both the host and parasite directly and contribute to temporal heterogeneities in parasite loads. We investigated the contributions of host and parasite traits as well as season on parasite loads in highveld mole-rats (Cryptomys hottentotus pretoriae). This cooperative breeder exhibits a reproductive division of labour and animals live in colonies of varying sizes that procreate seasonally. Mole-rats were parasitised by lice, mites, cestodes and nematodes with mites (Androlaelaps sp.) and cestodes (Mathevotaenia sp.) being the dominant ecto- and endoparasites, respectively. Sex and reproductive status contributed little to the observed parasite prevalence and abundances possibly as a result of the shared burrow system. Clear seasonal patterns of parasite prevalence and abundance emerged with peaks in summer for mites and in winter for cestodes. Group size correlated negatively with mite abundance while it had no effect on cestode burdens and group membership affected infestation with both parasites. We propose that the mode of transmission as well as social factors constrain parasite propagation generating parasite patterns deviating from those commonly predicted. PMID- 22069482 TI - Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and Abeta oligomerization. AB - Accumulation and deposition of beta-amyloid protein (Abeta) are the hallmark features of Alzheimer's disease. The inhalation anesthetic isoflurane has been shown to induce caspase activation and increase Abeta accumulation. In addition, recent studies suggest that isoflurane may directly promote the formation of cytotoxic soluble Abeta oligomers, which are thought to be the key pathological species in AD. In contrast, propofol, the most commonly used intravenous anesthetic, has been reported to have neuroprotective effects. We therefore set out to compare the effects of isoflurane and propofol alone and in combination on caspase-3 activation and Abeta oligomerization in vitro and in vivo. Naive and stably-transfected H4 human neuroglioma cells that express human amyloid precursor protein, the precursor for Abeta; neonatal mice; and conditioned cell culture media containing secreted human Abeta40 or Abeta42 were treated with isoflurane and/or propofol. Here we show for the first time that propofol can attenuate isoflurane-induced caspase-3 activation in cultured cells and in the brain tissues of neonatal mice. Furthermore, propofol-mediated caspase inhibition occurred when there were elevated levels of Abeta. Finally, isoflurane alone induces Abeta42, but not Abeta40, oligomerization, and propofol can inhibit the isoflurane-mediated oligomerization of Abeta42. These data suggest that propofol may mitigate the caspase-3 activation by attenuating the isoflurane-induced Abeta42 oligomerization. Our findings provide novel insights into the possible mechanisms of isoflurane-induced neurotoxicity that may aid in the development of strategies to minimize potential adverse effects associated with the administration of anesthetics to patients. PMID- 22069483 TI - Quantification of optic disc edema during exposure to high altitude shows no correlation to acute mountain sickness. AB - BACKGROUND: The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. METHODOLOGY/PRINCIPAL FINDINGS: A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3(r)) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO2) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3(r) used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p<0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO2 or HR. CONCLUSIONS/SIGNIFICANCE: Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO2 and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS. PMID- 22069484 TI - Bacillus subtilis MreB orthologs self-organize into filamentous structures underneath the cell membrane in a heterologous cell system. AB - Actin-like bacterial cytoskeletal element MreB has been shown to be essential for the maintenance of rod cell shape in many bacteria. MreB forms rapidly remodelling helical filaments underneath the cell membrane in Bacillus subtilis and in other bacterial cells, and co-localizes with its two paralogs, Mbl and MreBH. We show that MreB localizes as dynamic bundles of filaments underneath the cell membrane in Drosophila S2 Schneider cells, which become highly stable when the ATPase motif in MreB is modified. In agreement with ATP-dependent filament formation, the depletion of ATP in the cells lead to rapid dissociation of MreB filaments. Extended induction of MreB resulted in the formation of membrane protrusions, showing that like actin, MreB can exert force against the cell membrane. Mbl also formed membrane associated filaments, while MreBH formed filaments within the cytosol. When co-expressed, MreB, Mbl and MreBH built up mixed filaments underneath the cell membrane. Membrane protein RodZ localized to endosomes in S2 cells, but localized to the cell membrane when co-expressed with Mbl, showing that bacterial MreB/Mbl structures can recruit a protein to the cell membrane. Thus, MreB paralogs form a self-organizing and dynamic filamentous scaffold underneath the membrane that is able to recruit other proteins to the cell surface. PMID- 22069485 TI - Biophysical analysis of apolipoprotein E3 variants linked with development of type III hyperlipoproteinemia. AB - BACKGROUND: Apolipoprotein E (apoE) is a major protein of the lipoprotein transport system that plays important roles in lipid homeostasis and protection from atherosclerosis. ApoE is characterized by structural plasticity and thermodynamic instability and can undergo significant structural rearrangements as part of its biological function. Mutations in the 136-150 region of the N terminal domain of apoE, reduce its low density lipoprotein (LDL) receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP) in humans. However, the LDL-receptor binding defects for these apoE variants do not correlate well with the severity of dyslipidemia, indicating that these variants may carry additional properties that contribute to their pathogenic potential. METHODOLOGY/PRINCIPAL FINDINGS: In this study we examined whether three type III HLP predisposing apoE3 variants, namely R136S, R145C and K146E affect the biophysical properties of the protein. Circular dichroism (CD) spectroscopy revealed that these mutations do not significantly alter the secondary structure of the protein. Thermal and chemical unfolding analysis revealed small thermodynamic alterations in each variant compared to wild-type apoE3, as well as effects in the reversibility of the unfolding transition. All variants were able to remodel multillamelar 1,2-Dimyristoyl-sn glycero-3-phosphocholine (DMPC) vesicles, but R136S and R145C had reduced kinetics. Dynamic light scattering analysis indicated that the variant R136S exists in a higher-order oligomerization state in solution. Finally, 1 anilinonaphthalene-8-sulfonic acid (ANS) binding suggested that the variant R145C exposes a larger amount of hydrophobic surface to the solvent. CONCLUSIONS/SIGNIFICANCE: Overall, our findings suggest that single amino acid changes in the functionally important region 136-150 of apoE3 can affect the molecule's stability and conformation in solution and may underlie functional consequences. However, the magnitude and the non-concerted nature of these changes, make it unlikely that they constitute a distinct unifying mechanism leading to type III HLP pathogenesis. PMID- 22069486 TI - Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis. AB - In acute lymphoblastic leukemia (ALL) patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null) mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis. PMID- 22069487 TI - CD44 upregulation in E-cadherin-negative esophageal cancers results in cell invasion. AB - E-cadherin is frequently lost during epithelial-mesenchymal transition and the progression of epithelial tumorigenesis. We found a marker of epithelial mesenchymal transition, CD44, upregulated in response to functional loss of E cadherin in esophageal cell lines and cancer. Loss of E-cadherin expression correlates with increased expression of CD44 standard isoform. Using an organotypic reconstruct model, we show increased CD44 expression in areas of cell invasion is associated with MMP-9 at the leading edge. Moreover, Activin A increases cell invasion through CD44 upregulation after E-cadherin loss. Taken together, our results provide functional evidence of CD44 upregulation in esophageal cancer invasion. PMID- 22069488 TI - Structural, stability, dynamic and binding properties of the ALS-causing T46I mutant of the hVAPB MSP domain as revealed by NMR and MD simulations. AB - T46I is the second mutation on the hVAPB MSP domain which was recently identified from non-Brazilian kindred to cause a familial amyotrophic lateral sclerosis (ALS). Here using CD, NMR and molecular dynamics (MD) simulations, we characterized the structure, stability, dynamics and binding capacity of the T46I MSP domain. The results reveal: 1) unlike P56S which we previously showed to completely eliminate the native MSP structure, T46I leads to no significant disruption of the native secondary and tertiary structures, as evidenced from its far-UV CD spectrum, as well as Calpha and Cbeta NMR chemical shifts. 2) Nevertheless, T46I does result in a reduced thermodynamic stability and loss of the cooperative urea-unfolding transition. As such, the T46I-MSP domain is more prone to aggregation than WT at high protein concentrations and temperatures in vitro, which may become more severe in the crowded cellular environments. 3) T46I only causes a 3-fold affinity reduction to the Nir2 peptide, but a significant elimination of its binding to EphA4. 4) EphA4 and Nir2 peptide appear to have overlapped binding interfaces on the MSP domain, which strongly implies that two signaling networks may have a functional interplay in vivo. 5) As explored by both H/D exchange and MD simulations, the MSP domain is very dynamic, with most loop residues and many residues on secondary structures highly fluctuated or/and exposed to bulk solvent. Although T46I does not alter overall dynamics, it does trigger increased dynamics of several local regions of the MSP domain which are implicated in binding to EphA4 and Nir2 peptide. Our study provides the structural and dynamic understanding of the T46I-causing ALS; and strongly highlights the possibility that the interplay of two signaling networks mediated by the FFAT-containing proteins and Eph receptors may play a key role in ALS pathogenesis. PMID- 22069489 TI - Activation of Sirt1 by resveratrol inhibits TNF-alpha induced inflammation in fibroblasts. AB - Inflammation is one of main mechanisms of autoimmune disorders and a common feature of most diseases. Appropriate suppression of inflammation is a key resolution to treat the diseases. Sirtuin1 (Sirt1) has been shown to play a role in regulation of inflammation. Resveratrol, a potent Sirt1 activator, has anti inflammation property. However, the detailed mechanism is not fully understood. In this study, we investigated the anti-inflammation role of Sirt1 in NIH/3T3 fibroblast cell line. Upregulation of matrix metalloproteinases 9 (MMP-9), interleukin-1beta (IL-1beta), IL-6 and inducible nitric oxide synthase (iNOS) were induced by tumor necrosis factor alpha (TNF-alpha) in 3T3 cells and resveratrol suppressed overexpression of these pro-inflammatory molecules in a dose-dependent manner. Knockdown of Sirt1 by RNA interference caused 3T3 cells susceptible to TNF-alpha stimulation and diminished anti-inflammatory effect of resveratrol. We also explored potential anti-inflammatory mechanisms of resveratrol. Resveratrol reduced NF-kappaB subunit RelA/p65 acetylation, which is notably Sirt1 dependent. Resveratrol also attenuated phosphorylation of mammalian target of rapamycin (mTOR) and S6 ribosomal protein (S6RP) while ameliorating inflammation. Our data demonstrate that resveratrol inhibits TNF-alpha-induced inflammation via Sirt1. It suggests that Sirt1 is an efficient target for regulation of inflammation. This study provides insight on treatment of inflammation-related diseases. PMID- 22069490 TI - A single nucleotide in stem loop II of 5'-untranslated region contributes to virulence of enterovirus 71 in mice. AB - BACKGROUND: Enterovirus 71 (EV71) has emerged as a neuroinvasive virus responsible for several large outbreaks in the Asia-Pacific region while virulence determinant remains unexplored. PRINCIPAL FINDINGS: In this report, we investigated increased virulence of unadapted EV71 clinical isolate 237 as compared with isolate 4643 in mice. A fragment 12 nucleotides in length in stem loop (SL) II of 237 5'-untranslated region (UTR) visibly reduced survival time and rate in mice was identified by constructing a series of infectious clones harboring chimeric 5'-UTR. In cells transfected with bicistronic plasmids, and replicon RNAs, the 12-nt fragment of isolate 237 enhanced translational activities and accelerated replication of subgenomic EV71. Finally, single nucleotide change from cytosine to uridine at base 158 in this short fragment of 5'-UTR was proven to reduce viral translation and EV71 virulence in mice. Results collectively indicated a pivotal role of novel virulence determinant C158 on virus translation in vitro and EV71 virulence in vivo. CONCLUSIONS: These results presented the first reported virulence determinant in EV71 5'-UTR and first position discovered from unadapted isolates. PMID- 22069491 TI - Pseudomonas aeruginosa elastase provides an escape from phagocytosis by degrading the pulmonary surfactant protein-A. AB - Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute pneumonitis in immunocompromised patients and chronic lung infections in individuals with cystic fibrosis and other bronchiectasis. Over 75% of clinical isolates of P. aeruginosa secrete elastase B (LasB), an elastolytic metalloproteinase that is encoded by the lasB gene. Previously, in vitro studies have demonstrated that LasB degrades a number of components in both the innate and adaptive immune systems. These include surfactant proteins, antibacterial peptides, cytokines, chemokines and immunoglobulins. However, the contribution of LasB to lung infection by P. aeruginosa and to inactivation of pulmonary innate immunity in vivo needs more clarification. In this study, we examined the mechanisms underlying enhanced clearance of the DeltalasB mutant in mouse lungs. The DeltalasB mutant was attenuated in virulence when compared to the wild-type strain PAO1 during lung infection in SP-A+/+ mice. However, the DeltalasB mutant was as virulent as PAO1 in the lungs of SP-A-/- mice. Detailed analysis showed that the DeltalasB mutant was more susceptible to SP-A-mediated opsonization but not membrane permeabilization. In vitro and in vivo phagocytosis experiments revealed that SP-A augmented the phagocytosis of DeltalasB mutant bacteria more efficiently than the isogenic wild-type PAO1. The DeltalasB mutant was found to have a severely reduced ability to degrade SP-A, consequently making it unable to evade opsonization by the collectin during phagocytosis. These results suggest that P. aeruginosa LasB protects against SP-A-mediated opsonization by degrading the collectin. PMID- 22069493 TI - Recent loss of vitamin C biosynthesis ability in bats. AB - The traditional assumption that bats cannot synthesize vitamin C (Vc) has been challenged recently. We have previously shown that two Old World bat species (Rousettus leschenaultii and Hipposideros armiger) have functional L gulonolactone oxidase (GULO), an enzyme that catalyzes the last step of Vc biosynthesis de novo. Given the uncertainties surrounding when and how bats lost GULO function, exploration of gene evolutionary patterns is needed. We therefore sequenced GULO genes from 16 bat species in 5 families, aiming to establish their evolutionary histories. In five cases we identified pseudogenes for the first time, including two cases in the genus Pteropus (P. pumilus and P. conspicillatus) and three in family Hipposideridae (Coelops frithi, Hipposideros speoris, and H. bicolor). Evolutionary analysis shows that the Pteropus clade has the highest omega ratio and has been subjected to relaxed selection for less than 3 million years. Purifying selection acting on the pseudogenized GULO genes of roundleaf bats (family Hipposideridae) suggests they have lost the ability to synthesize Vc recently. Limited mutations in the reconstructed GULO sequence of the ancestor of all bats contrasts with the many mutations in the ancestral sequence of recently emerged Pteropus bats. We identified at least five mutational steps that were then related to clade origination times. Together, our results suggest that bats lost the ability to biosynthesize vitamin C recently by exhibiting stepwise mutation patterns during GULO evolution that can ultimately lead to pseudogenization. PMID- 22069492 TI - Stanniocalcin-1 regulates re-epithelialization in human keratinocytes. AB - Stanniocalcin-1 (STC1), a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re epithelialization is a critical step that involves keratinocyte lamellipodia (e lam) formation, followed by cell migration. In this study, staurosporine (STS) treatment induced human keratinocyte (HaCaT) e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK), the surge of intracellular calcium level [Ca2+]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca2+]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca2+]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3beta by lithium chloride (LiCl) could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing. PMID- 22069494 TI - Characterization of a truncated metabotropic glutamate receptor in a primitive metazoan, the parasitic flatworm Schistosoma mansoni. AB - A novel glutamate-binding protein was identified in Schistosoma mansoni. The protein (SmGBP) is related to metabotropic glutamate receptors from other species and has a predicted glutamate binding site located within a Venus Flytrap module but it lacks the heptahelical transmembrane segment that normally characterizes these receptors. The SmGBP cDNA was cloned, verified by 5' and 3' Rapid Amplification of cDNA Ends (RACE) and shown to be polyadenylated at the 3'end, suggesting the transcript is full-length. The cloned cDNA was subsequently expressed in bacteria and shown to encode a functional glutamate-binding protein. Other studies, using a specific peptide antibody, determined that SmGBP exists in two forms, a monomer of the expected size and a stable but non-covalent dimer. The monomer and dimer are both present in the membrane fraction of S. mansoni and are resistant to extraction with high-salt, alkaline pH and urea, suggesting SmGBP is either an integral membrane protein or a peripheral protein that is tightly associated with the membrane. Surface biotinylation experiments combined with western blot analyses and confocal immunolocalization revealed that SmGBP localized to the surface membranes of adult male schistosomes, especially the dorsal tubercles. In contrast, we detected little or no expression of SmGBP either in the females or larval stages. A comparative quantitative PCR analysis confirmed that the level of SmGBP expression is several-fold higher in male worms than cercariae, and it is barely detectable in adult females. Together, the results identify SmGBP as a new type of schistosome glutamate receptor that is both gender- and stage-specific. The high-level expression of this protein in the male tubercles suggests a possible role in host-parasite interaction. PMID- 22069496 TI - Mll5 is required for normal spermatogenesis. AB - BACKGROUND: Mll5 is currently a member of the Mll family of SET domain histone methyltransferase proteins but studies have also showed that it could be part of the SET3 branch of proteins. Recently, constitutive knock out animal studies have shown that Mll5 is required for proper haematopoietic stem cell differentiation, and loss of Mll5 results in synthetic lethality for genome de-methylation. Mll5 deficient male mice are infertile and here we analyse the consequences of Mll5 deficiency for spermatogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Mll5 deficient male mice, but not female mice, are infertile. Here we show using RNA in-situ hybridization that Mll5 is expressed in the germ cells of the testes of wild type mice. Consistent with the expression of Mll5, we demonstrate by electron microscopy, video microscopy and in vitro fertilisation techniques that Mll5 deficient mice have defects in terminal maturation and packaging of sperm. The defects seen include detachment of the acrosomal cap and impaired excess cytoplasm removal. Functional tests of sperm motility show a lack of progressive motility of spermatozoa from Mll5 deficient animals. None of these defects could be rescued by in vitro fertilization. Using microarray analysis we show that transcripts implicated in spermatogenesis are dysregulated. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a clear role of Mll5 in mammalian spermatogenesis at the level of terminal differentiation providing further support for its classification in the SET3 branch of proteins. Moreover, this study identifies Tlk2, Utx, Gpr64, Sult4a1, Rap2ip, Vstm2 and HoxA10 as possible Mll5 targets that together may account for the observed spermatozoa maturation defects. PMID- 22069495 TI - Comparative transcriptional analysis reveals differential gene expression between asymmetric and symmetric zygotic divisions in tobacco. AB - Asymmetric cell divisions occur widely during many developmental processes in plants. In most angiosperms, the first zygotic cell division is asymmetric resulting in two daughter cells of unequal size and with distinct fates. However, the critical molecular mechanisms regulating this division remain unknown. Previously we showed that treatment of tobacco zygotes with beta-glucosyl Yariv (betaGlcY) could dramatically alter the first zygotic asymmetric division to produce symmetric two-celled proembryos. In the present study, we isolated zygotes and two-celled asymmetric proembryos in vivo by micromanipulation, and obtained symmetric, two-celled proembryos by in vitro cell cultures. Using suppression-subtractive hybridization (SSH) and macroarray analysis differential gene expression between the zygote and the asymmetric and symmetric two-celled proembryos was investigated. After sequencing of the differentially expressed clones, a total of 1610 EST clones representing 685 non-redundant transcripts were obtained. Gene ontology (GO) term analysis revealed that these transcripts include those involved in physiological processes such as response to stimulus, regulation of gene expression, and localization and formation of anatomical structures. A homology search against known genes from Arabidopsis indicated that some of the above transcripts are involved in asymmetric cell division and embryogenesis. Quantitative real-time PCR confirmed the up- or down-regulation of the selected candidate transcripts during zygotic division. A few of these transcripts were expressed exclusively in the zygote, or in either type of the two-celled proembryos. Expression analyses of select genes in different tissues and organs also revealed potential roles of these transcripts in fertilization, seed maturation and organ development. The putative roles of few of the identified transcripts in the regulation of zygotic division are discussed. Further functional work on these candidate transcripts will provide important information for understanding asymmetric zygotic division, generation of apical basal polarity and cell fate decisions during early embryogenesis. PMID- 22069497 TI - The temporal order of genetic and pathway alterations in tumorigenesis. AB - Cancer evolves through the accumulation of mutations, but the order in which mutations occur is poorly understood. Inference of a temporal ordering on the level of genes is challenging because clinically and histologically identical tumors often have few mutated genes in common. This heterogeneity may at least in part be due to mutations in different genes having similar phenotypic effects by acting in the same functional pathway. We estimate the constraints on the order in which alterations accumulate during cancer progression from cross-sectional mutation data using a probabilistic graphical model termed Hidden Conjunctive Bayesian Network (H-CBN). The possible orders are analyzed on the level of genes and, after mapping genes to functional pathways, also on the pathway level. We find stronger evidence for pathway order constraints than for gene order constraints, indicating that temporal ordering results from selective pressure acting at the pathway level. The accumulation of changes in core pathways differs among cancer types, yet a common feature is that progression appears to begin with mutations in genes that regulate apoptosis pathways and to conclude with mutations in genes involved in invasion pathways. H-CBN models provide a quantitative and intuitive model of tumorigenesis showing that the genetic events can be linked to the phenotypic progression on the level of pathways. PMID- 22069498 TI - Capsomer vaccines protect mice from vaginal challenge with human papillomavirus. AB - Capsomers were produced in bacteria as glutathione-S-transferase (GST) fusion proteins with human papillomavirus type 16 L1 lacking the first nine and final 29 residues (GST-HPV16L1Delta) alone or linked with residues 13-47 of HPV18, HPV31 and HPV45 L2 in tandem (GST-HPV16L1Delta-L2x3). Subcutaneous immunization of mice with GST-HPV16L1Delta or GST-HPV16L1Delta-L2x3 in alum and monophosphoryl lipid A induced similarly high titers of HPV16 neutralizing antibodies. GST-HPV16L1Delta L2x3 also elicited moderate L2-specific antibody titers. Intravaginal challenge studies showed that immunization of mice with GST-HPV16 L1Delta or GST HPV16L1Delta-L2x3 capsomers, like Cervarix(r), provided complete protection against HPV16. Conversely, vaccination with GST-HPV16 L1Delta capsomers failed to protect against HPV18 challenge, whereas mice immunized with either GST HPV16L1Delta-L2x3 capsomers or Cervarix(r) were each completely protected. Thus, while the L2-specific response was moderate, it did not interfere with immunity to L1 in the context of GST-HPV16L1Delta-L2x3 and is sufficient to mediate L2 dependent protection against an experimental vaginal challenge with HPV18. PMID- 22069499 TI - A molecular phylogeny of bivalve mollusks: ancient radiations and divergences as revealed by mitochondrial genes. AB - BACKGROUND: Bivalves are very ancient and successful conchiferan mollusks (both in terms of species number and geographical distribution). Despite their importance in marine biota, their deep phylogenetic relationships were scarcely investigated from a molecular perspective, whereas much valuable work has been done on taxonomy, as well as phylogeny, of lower taxa. METHODOLOGY/PRINCIPAL FINDINGS: Here we present a class-level bivalve phylogeny with a broad sample of 122 ingroup taxa, using four mitochondrial markers (MT-RNR1, MT-RNR2, MT-CO1, MT CYB). Rigorous techniques have been exploited to set up the dataset, analyze phylogenetic signal, and infer a single final tree. In this study, we show the basal position of Opponobranchia to all Autobranchia, as well as of Palaeoheterodonta to the remaining Autobranchia, which we here propose to call Amarsipobranchia. Anomalodesmata were retrieved as monophyletic and basal to (Heterodonta + Pteriomorphia). CONCLUSIONS/SIGNIFICANCE: Bivalve morphological characters were traced onto the phylogenetic trees obtained from the molecular analysis; our analysis suggests that eulamellibranch gills and heterodont hinge are ancestral characters for all Autobranchia. This conclusion would entail a re evaluation of bivalve symplesiomorphies. PMID- 22069500 TI - Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation. AB - It has been hypothesised that substance P (SP) may be produced by primary fibroblastic tendon cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hypercellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A cell culture model of primary human tendon cells was used. The vast majority of tendon cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these cells. Gene expression analyses showed that mechanical loading (strain) of tendon cell cultures using the FlexCell(c) technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded tendon cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10-7 M. SP exposure furthermore resulted in increased cell metabolism, increased cell viability, and increased cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R. PMID- 22069501 TI - Modulation of synaptic plasticity by stress hormone associates with plastic alteration of synaptic NMDA receptor in the adult hippocampus. AB - Stress exerts a profound impact on learning and memory, in part, through the actions of adrenal corticosterone (CORT) on synaptic plasticity, a cellular model of learning and memory. Increasing findings suggest that CORT exerts its impact on synaptic plasticity by altering the functional properties of glutamate receptors, which include changes in the motility and function of alpha-amino-3 hydroxy-5-methylisoxazole-4-propionic acid subtype of glutamate receptor (AMPAR) that are responsible for the expression of synaptic plasticity. Here we provide evidence that CORT could also regulate synaptic plasticity by modulating the function of synaptic N-methyl-D-aspartate receptors (NMDARs), which mediate the induction of synaptic plasticity. We found that stress level CORT applied to adult rat hippocampal slices potentiated evoked NMDAR-mediated synaptic responses within 30 min. Surprisingly, following this fast-onset change, we observed a slow onset (>1 hour after termination of CORT exposure) increase in synaptic expression of GluN2A-containing NMDARs. To investigate the consequences of the distinct fast- and slow-onset modulation of NMDARs for synaptic plasticity, we examined the formation of long-term potentiation (LTP) and long-term depression (LTD) within relevant time windows. Paralleling the increased NMDAR function, both LTP and LTD were facilitated during CORT treatment. However, 1-2 hours after CORT treatment when synaptic expression of GluN2A-containing NMDARs is increased, bidirectional plasticity was no longer facilitated. Our findings reveal the remarkable plasticity of NMDARs in the adult hippocampus in response to CORT. CORT-mediated slow-onset increase in GluN2A in hippocampal synapses could be a homeostatic mechanism to normalize synaptic plasticity following fast-onset stress-induced facilitation. PMID- 22069502 TI - The JAK-STAT pathway controls Plasmodium vivax load in early stages of Anopheles aquasalis infection. AB - Malaria affects 300 million people worldwide every year and 450,000 in Brazil. In coastal areas of Brazil, the main malaria vector is Anopheles aquasalis, and Plasmodium vivax is responsible for the majority of malaria cases in the Americas. Insects possess a powerful immune system to combat infections. Three pathways control the insect immune response: Toll, IMD, and JAK-STAT. Here we analyze the immune role of the A. aquasalis JAK-STAT pathway after P. vivax infection. Three genes, the transcription factor Signal Transducers and Activators of Transcription (STAT), the regulatory Protein Inhibitors of Activated STAT (PIAS) and the Nitric Oxide Synthase enzyme (NOS) were characterized. Expression of STAT and PIAS was higher in males than females and in eggs and first instar larvae when compared to larvae and pupae. RNA levels for STAT and PIAS increased 24 and 36 hours (h) after P. vivax challenge. NOS transcription increased 36 h post infection (hpi) while this protein was already detected in some midgut epithelial cells 24 hpi. Imunocytochemistry experiments using specific antibodies showed that in non-infected insects STAT and PIAS were found mostly in the fat body, while in infected mosquitoes the proteins were found in other body tissues. The knockdown of STAT by RNAi increased the number of oocysts in the midgut of A. aquasalis. This is the first clear evidence for the involvement of a specific immune pathway in the interaction of the Brazilian malaria vector A. aquasalis with P. vivax, delineating a potential target for the future development of disease controlling strategies. PMID- 22069503 TI - Sleeping sickness in travelers - do they really sleep? AB - The number of imported Human African Trypanosomiasis (HAT) cases in non-endemic countries has increased over the last years. The objective of this analysis is to describe the clinical presentation of HAT in Caucasian travelers. Literature was screened (MEDLINE, Pubmed) using the terms "Human African Trypanosomiasis", "travelers" and "expatriates"; all European languages except Slavic ones were included. Publications without clinical description of patients were only included in the epidemiological analysis. Forty-five reports on Caucasians with T.b. rhodesiense and 15 with T.b. gambiense infections were included in the analysis of the clinical parameters. Both species have presented with fever (T.b. rhodesiense 97.8% and T.b. gambiense 93.3%), headache (50% each) and a trypanosomal chancre (T.b. rhodesiense 84.4%, T.b. gambiense 46.7%). While sleeping disorders dominate the clinical presentation of HAT in endemic regions, there have been only rare reports in travelers: insomnia (T.b. rhodesiense 7.1%, T.b. gambiense 21.4%), diurnal somnolence (T.b. rhodesiense 4.8%, T.b. gambiense none). Surprisingly, jaundice has been seen in 24.2% of the Caucasian T.b. rhodesiense patients, but has never been described in HAT patients in endemic regions. These results contrast to the clinical presentation of T.b. gambiense and T.b. rhodesiense HAT in Africans in endemic regions, where the presentation of chronic T.b. gambiense and acute T.b. rhodesiense HAT is different. The analysis of 14 reports on T.b. gambiense HAT in Africans living in a non-endemic country shows that neurological symptoms such as somnolence (46.2%), motor deficit (64.3%) and reflex anomalies (14.3%) as well as psychiatric symptoms such as hallucinations (21.4%) or depression (21.4%) may dominate the clinical picture. Often, the diagnosis has been missed initially: some patients have even been hospitalized in psychiatric clinics. In travelers T.b. rhodesiense and gambiense present as acute illnesses and chancres are frequently seen. The diagnosis of HAT in Africans living outside the endemic region is often missed or delayed, leading to presentation with advanced stages of the disease. PMID- 22069504 TI - Cell-associated flagella enhance the protection conferred by mucosally administered attenuated Salmonella Paratyphi A vaccines. AB - BACKGROUND: Antibiotic-resistant Salmonella enterica serovar Paratyphi A, the agent of paratyphoid A fever, poses an emerging public health dilemma in endemic areas of Asia and among travelers, as there is no licensed vaccine. Integral to our efforts to develop a S. Paratyphi A vaccine, we addressed the role of flagella as a potential protective antigen by comparing cell-associated flagella with exported flagellin subunits expressed by attenuated strains. METHODOLOGY: S. Paratyphi A strain ATCC 9150 was first deleted for the chromosomal guaBA locus, creating CVD 1901. Further chromosomal deletions in fliD (CVD 1901D) or flgK (CVD 1901K) were then engineered, resulting in the export of unpolymerized FliC, without impairing its overall expression. The virulence of the resulting isogenic strains was examined using a novel mouse LD(50) model to accommodate the human host restricted S. Paratyphi A. The immunogenicity of the attenuated strains was then tested using a mouse intranasal model, followed by intraperitoneal challenge with wildtype ATCC 9150. RESULTS: Mucosal (intranasal) immunization of mice with strain CVD 1901 expressing cell-associated flagella conferred superior protection (vaccine efficacy [VE], 90%) against a lethal intraperitoneal challenge, compared with the flagellin monomer-exporting mutants CVD 1901K (30% VE) or CVD 1901D (47% VE). The superior protection induced by CVD 1901 with its cell-attached flagella was associated with an increased IgG2a:IgG1 ratio of FliC-specific antibodies with enhanced opsonophagocytic capacity. CONCLUSIONS: Our results clearly suggest that enhanced anti-FliC antibody-mediated clearance of S. Paratyphi A by phagocytic cells, induced by vaccines expressing cell-associated rather than exported FliC, might be contributing to the vaccine-induced protection from S. Paratyphi A challenge in vivo. We speculate that an excess of IgG1 anti-FliC antibodies induced by the exported FliC may compete with the IgG2a subtype and block binding to specific phagocyte Fc receptors that are critical for clearing an S. Paratyphi A infection. PMID- 22069505 TI - Crystal structure of the complex mAb 17.2 and the C-terminal region of Trypanosoma cruzi P2beta protein: implications in cross-reactivity. AB - Patients with Chronic Chagas' Heart Disease possess high levels of antibodies against the carboxyl-terminal end of the ribosomal P2beta protein of Trypanosoma cruzi (TcP2beta). These antibodies, as well as the murine monoclonal antibody (mAb) 17.2, recognize the last 13 amino acids of TcP2beta (called the R13 epitope: EEEDDDMGFGLFD) and are able to cross-react with, and stimulate, the beta1 adrenergic receptor (beta1-AR). Indeed, the mAb 17.2 was able to specifically detect human beta1-AR, stably transfected into HEK cells, by flow cytometry and to induce repolarisation abnormalities and first degree atrioventricular conduction block after passive transfer to naive mice. To study the structural basis of this cross-reactivity, we determined the crystal structure of the Fab region of the mAb 17.2 alone at 2.31 A resolution and in complex with the R13 peptide at 1.89 A resolution. We identified as key contact residues on R13 peptide Glu3, Asp6 and Phe9 as was previously shown by alanine scanning. Additionally, we generated a model of human beta1-AR to elucidate the interaction with anti-R13 antibodies. These data provide an understanding of the molecular basis of cross-reactive antibodies induced by chronic infection with Trypanosoma cruzi. PMID- 22069506 TI - Challenges in estimating insecticide selection pressures from mosquito field data. AB - Insecticide resistance has the potential to compromise the enormous effort put into the control of dengue and malaria vector populations. It is therefore important to quantify the amount of selection acting on resistance alleles, their contributions to fitness in heterozygotes (dominance) and their initial frequencies, as a means to predict the rate of spread of resistance in natural populations. We investigate practical problems of obtaining such estimates, with particular emphasis on Mexican populations of the dengue vector Aedes aegypti. Selection and dominance coefficients can be estimated by fitting genetic models to field data using maximum likelihood (ML) methodology. This methodology, although widely used, makes many assumptions so we investigated how well such models perform when data are sparse or when spatial and temporal heterogeneity occur. As expected, ML methodologies reliably estimated selection and dominance coefficients under idealised conditions but it was difficult to recover the true values when datasets were sparse during the time that resistance alleles increased in frequency, or when spatial and temporal heterogeneity occurred. We analysed published data on pyrethroid resistance in Mexico that consists of the frequency of a Ile1,016 mutation. The estimates for selection coefficient and initial allele frequency on the field dataset were in the expected range, dominance coefficient points to incomplete dominance as observed in the laboratory, although these estimates are accompanied by strong caveats about possible impact of spatial and temporal heterogeneity in selection. PMID- 22069508 TI - Cortical actin dynamics: Generating randomness by formin(g) and moving. AB - The actin cytoskeleton plays essential roles in cell polarization and cell morphogenesis of the budding yeast Saccharomyces cerevisiae. Yeast cells utilize formin-generated actin cables as tracks for polarized transport, which forms the basis for a positive feedback loop driving Cdc42-dependent cell polarization. Previous studies on cable organization mostly focused on polarized actin cables in budded cells and their role as relatively static tracks for myosin-dependent organelle transport. Using quantitative live cell imaging, we have recently characterized the dynamics of cortical actin cables throughout the yeast cell cycle. Surprisingly, randomly oriented actin cables in G(1) cells exhibited the highest level of dynamics, while cable dynamics was markedly slowed down upon cell polarization. We further demonstrated that the rapid dynamics of randomly oriented cables were driven by the formin Bni1 and Myosin V. Our data suggested a precise spatio-temporal regulation of the two yeast formins, as well as an unexpected mechanism of actin cable rearrangement through myosins. Here we discuss the immediate significance of these findings, which illustrates the importance of generating randomness for cellular organization. PMID- 22069507 TI - Tropomyosin isoforms and reagents. AB - Tropomyosins are rod-like dimers which form head-to-tail polymers along the length of actin filaments and regulate the access of actin binding proteins to the filaments.1 The diversity of tropomyosin isoforms, over 40 in mammals, and their role in an increasing number of biological processes presents a challenge both to experienced researchers and those new to this field. The increased appreciation that the role of these isoforms expands beyond that of simply stabilizing actin filaments has lead to a surge of reagents and techniques to study their function and mechanisms of action. This report is designed to provide a basic guide to the genes and proteins and the availability of reagents which allow effective study of this family of proteins. We highlight the value of combining multiple techniques to better evaluate the function of different tm isoforms and discuss the limitations of selected reagents. Brief background material is included to demystify some of the unfortunate complexity regarding this multi-gene family of proteins including the unconventional nomenclature of the isoforms and the evolutionary relationships of isoforms between species. Additionally, we present step-by-step detailed experimental protocols used in our laboratory to assist new comers to the field and experts alike. PMID- 22069509 TI - Coupling of the mechanotransduction machinery and F-actin polymerization in the cochlear hair bundles. AB - Mechanoelectrical transduction (MET), the conversion of mechanical stimuli into electrical signals operated by the sensory cells of the inner ear, enables hearing and balance perception. Crucial to this process are the tip-links, oblique fibrous filaments that interconnect the actin-filled stereocilia of different rows within the hair bundle, and mechanically gate MET channels. In a recent study, we observed a complete regression of stereocilia from the short and medium but not the tall row upon the disappearance of the tip-links caused by the loss of one of their components, cadherin-23, or of one of their anchoring proteins, sans, in the auditory organs of engineered mutant mice. This indicates the existence of a coupling between the MET and F-actin polymerization machineries at the tips of the short and medium stereocilia rows in cochlear hair bundles. Here, we first present our findings in the mutant mice, and then discuss the possible effects of the tip-link tension on stereocilia F-actin polymerization, acting either directly or through Ca(2+)-dependent mechanisms that involve the gating of MET channels. PMID- 22069510 TI - The sarcoplasmic reticulum: Actin and tropomodulin hit the links. AB - Skeletal muscle exhibits strikingly regular intracellular sorting of actin and tropomodulin (Tmod) isoforms, which are essential for efficient muscle contraction. A recent study from our laboratory demonstrates that the skeletal muscle sarcoplasmic reticulum (SR) is associated with cytoplasmic gamma-actin (gamma(cyto)-actin) filaments, which are predominantly capped by Tmod3. When Tmod3 is experimentally induced to vacate its SR compartment, the cytoskeletal organization of SR-associated gamma(cyto)-actin is perturbed, leading to SR swelling, depressed SR Ca(2+) release and myofibril misalignment. Based on these findings, Tmod3-capped gamma(cyto)-actin filaments mechanically stabilize SR structure and regulate SR function via a novel lateral linkage. Furthermore, by placing these findings in the context of studies in nonmuscle cells, we conclude that Tmodcapped actin filaments are emerging as critical regulators of membrane stability and physiology in a broad assortment of cell types. PMID- 22069511 TI - Lymphocyte polarity, the immunological synapse and the scope of biological analogy. AB - Lymphocytes such as T cells, B cells and natural killer (NK) cells form specialized contacts, called immunological synapses, with other cells in order to engage in specific intercellular communication and killing. Synapse formation is associated with the polarization of the microtubule-organizing center (MTOC) toward the contact site, which enables the directional secretion of cytokines and lytic factors. Although MTOC reorientation to the synapse is crucial for lymphocyte function, it has been difficult to study because of technical constraints. We have developed a photoactivation and imaging strategy that enables high-resolution analysis of cytoskeletal dynamics in individual T cells. Using this approach, we have demonstrated that the lipid second messenger diacylglycerol plays a crucial role in promoting MTOC reorientation by recruiting three members of the protein kinase C family to the synapse. Here, I will discuss these results along with studies from other labs, which have explored the role of polarity-inducing protein complexes after synapse formation. I will also propose a two-step model for MTOC reorientation in lymphocytes that reflects what we now know about the subject. Finally, I will consider the extent to which lymphocyte polarity resembles analogous cell polarity systems in other cell types. PMID- 22069512 TI - Spectrin-adducin membrane skeleton: A missing link between epithelial junctions and the actin cytoskeletion? AB - Adherens junctions (AJs) and tight junctions (TJs) represent key adhesive structures that regulate the apico-basal polarity and barrier properties of epithelial layers. AJs and TJs readily undergo disassembly and reassembly during normal tissue remodeling and disruption of epithelial barriers in diseases. Such junctional plasticity depends on the orchestrated dynamics of the plasma membrane with its underlying F-actin cytoskeleton, however the interplay between these cellular structures remains poorly understood. Recent studies highlighted the spectrin-adducin-based membrane skeleton as an emerging regulator of AJ and TJ integrity and remodeling. Here we discuss new evidences implicating adducin, spectrin and other membrane skeleton proteins in stabilization of epithelial junctions and regulation of junctional dynamics. Based on the known ability of the membrane skeleton to link cortical actin filaments to the plasma membrane, we hypothesize that the spectrin-adducin network serves as a critical signal and force transducer from the actomyosin cytoskeleton to junctions during remodeling of AJs and TJs. PMID- 22069513 TI - Nuclear actin-related proteins take shape. AB - The function of nuclear actin is poorly understood. It is known to be a discrete component of several chromatin-modifying complexes. Nevertheless, filamentous forms of actin are important for various nuclear processes as well. Nuclear actin is often associated with nuclear actin-related protein Arp4 and other actin related proteins like Arp8 in the INO80 chromatin remodeler. We recently determined the crystal structure of S. cerevisiae Arp4 that explains why Arp4 is unable to form actin like filaments and shows that it is constitutively bound to an ATP nucleotide. More interestingly, in vitro activities of Arp4 and Arp8 seem to be directed towards stabilizing monomeric actin and to integrate it stoichiometrically into the INO80 complex. Based on this activity, we discuss possible roles of nuclear Arps in chromatin modifying complexes and in regulating more general aspects of nuclear actin dynamics. PMID- 22069514 TI - New insights into eyespot placement and assembly in Chlamydomonas. AB - Aspects of cellular architecture, such as cytoskeletal asymmetry cues, play critical roles in directing the placement of organelles and establishing the sites of their formation. In the model green alga Chlamydomonas, the photosensory eyespot occupies a defined position in relation to the flagella and microtubule cytoskeleton. Investigations into the cellular mechanisms of eyespot placement and assembly have aided our understanding of the interplay between cytoskeletal and plastid components of the cell. The eyespot, which must be assembled anew after each cell division, is a multi-layered organelle consisting of stacks of carotenoid-filled pigment granules in the chloroplast and rhodopsin photoreceptors in the plasma membrane. Placement of the eyespot is determined on both the latitudinal and longitudinal axes of the cell by the daughter four membered (D4) microtubule rootlet. Recent findings have contributed to the hypothesis that the eyespot photoreceptor molecules are directed from the Golgi to the daughter hemisphere of the cell and trafficked along the D4 microtubule rootlet. EYE2, a chloroplast-envelope protein, forms an elliptical patch together with the photoreceptors and establishes the site for assembly of the pigment granule arrays in the chloroplast, connecting the positioning information of the cytoskeleton to assembly of the pigment granule arrays in the chloroplast. PMID- 22069515 TI - Ras and Rho GTPases on the move: The RasGRF connection. AB - Metastasis involves tumor cells moving through tissues and crossing tissue boundaries, which requires cell migration, remodeling of cell-to-cell contacts and interactions with the extracellular matrix. Individual tumor cells move in three-dimensional environments with either a rounded "ameboid" or an elongated "mesenchymal" morphology. These two modes of movement are tightly regulated by Rho family GTPases: elongated movement requires activation of Rac1, whereas rounded movement engages specific Cdc42 and Rho signaling pathways. It has been known for some time that events unfolding downstream of Ras GTPases are also involved in regulating multiple aspects of cell migration and invasion. More recently, RasGRF2-a Ras activator-has been identified as a suppressor of rounded movement, by inhibiting the activation of Cdc42, independently of its capacity to activate Ras. Here, we discuss how Rho and Ras signals can either cooperate or oppose each other in the regulation of cell migration and invasion. PMID- 22069516 TI - Next-generation dengue vaccines: novel strategies currently under development. AB - Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed. PMID- 22069517 TI - Inhibition of geranylgeranyl transferase-I decreases cell viability of HTLV-1 transformed cells. AB - Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), an aggressive and highly chemoresistant malignancy. Rho family GTPases regulate multiple signaling pathways in tumorigenesis: cytoskeletal organization, transcription, cell cycle progression, and cell proliferation. Geranylgeranylation of Rho family GTPases is essential for cell membrane localization and activation of these proteins. It is currently unknown whether HTLV-1-transformed cells are preferentially sensitive to geranylgeranylation inhibitors, such as GGTI-298. In this report, we demonstrate that GGTI-298 decreased cell viability and induced G(2)/M phase accumulation of HTLV-1-transformed cells, independent of p53 reactivation. HTLV-1-LTR transcriptional activity was inhibited and Tax protein levels decreased following treatment with GGTI-298. Furthermore, GGTI-298 decreased activation of NF-kappaB, a downstream target of Rho family GTPases. These studies suggest that protein geranylgeranylation contributes to dysregulation of cell survival pathways in HTLV-1-transformed cells. PMID- 22069518 TI - Non-retroviral fossils in vertebrate genomes. AB - Although no physical fossils of viruses have been found, retroviruses are known to leave their molecular fossils in the genomes of their hosts, the so-called endogenous retroviral elements. These have provided us with important information about retroviruses in the past and their co-evolution with their hosts. On the other hand, because non-retroviral viruses were considered not to leave such fossils, even the existence of prehistoric non-retroviral viruses has been enigmatic. Recently, we discovered that elements derived from ancient bornaviruses, non-segmented, negative strand RNA viruses, are found in the genomes of several mammalian species, including humans. In addition, at approximately the same time, several endogenous elements of RNA viruses, DNA viruses and reverse-transcribing DNA viruses have been independently reported, which revealed that non-retroviral viruses have played significant roles in the evolution of their hosts and provided novel insights into virology and cell biology. Here we review non-retroviral virus-like elements in vertebrate genomes, non-retroviral integration and the knowledge obtained from these endogenous non retroviral virus-like elements. PMID- 22069519 TI - Next generation sequencing technologies for insect virus discovery. AB - Insects are commonly infected with multiple viruses including those that cause sublethal, asymptomatic, and latent infections. Traditional methods for virus isolation typically lack the sensitivity required for detection of such viruses that are present at low abundance. In this respect, next generation sequencing technologies have revolutionized methods for the discovery and identification of new viruses from insects. Here we review both traditional and modern methods for virus discovery, and outline analysis of transcriptome and small RNA data for identification of viral sequences. We will introduce methods for de novo assembly of viral sequences, identification of potential viral sequences from BLAST data, and bioinformatics for generating full-length or near full-length viral genome sequences. We will also discuss implications of the ubiquity of viruses in insects and in insect cell lines. All of the methods described in this article can also apply to the discovery of viruses in other organisms. PMID- 22069520 TI - Feline immunodeficiency virus (FIV) neutralization: a review. AB - One of the major obstacles that must be overcome in the design of effective lentiviral vaccines is the ability of lentiviruses to evolve in order to escape from neutralizing antibodies. The primary target for neutralizing antibodies is the highly variable viral envelope glycoprotein (Env), a glycoprotein that is essential for viral entry and comprises both variable and conserved regions. As a result of the complex trimeric nature of Env, there is steric hindrance of conserved epitopes required for receptor binding so that these are not accessible to antibodies. Instead, the humoral response is targeted towards decoy immunodominant epitopes on variable domains such as the third hypervariable loop (V3) of Env. For feline immunodeficiency virus (FIV), as well as the related human immunodeficiency virus-1 (HIV-1), little is known about the factors that lead to the development of broadly neutralizing antibodies. In cats infected with FIV and patients infected with HIV-1, only rarely are plasma samples found that contain antibodies capable of neutralizing isolates from other clades. In this review we examine the neutralizing response to FIV, comparing and contrasting with the response to HIV. We ask whether broadly neutralizing antibodies are induced by FIV infection and discuss the comparative value of studies of neutralizing antibodies in FIV infection for the development of more effective vaccine strategies against lentiviral infections in general, including HIV-1. PMID- 22069521 TI - Prior virus exposure alters the long-term landscape of viral replication during feline lentiviral infection. AB - We developed a feline model of lentiviral cross-species transmission using a puma lentivirus (PLV or FIV(Pco)) which infects domestic cats but does not cause disease. Infection with PLV protects cats from CD4+ T-cell decline caused by subsequent infection with virulent feline immunodeficiency virus (FIV). Previous studies implicate innate immune and/or cellular restriction mechanisms for FIV disease attenuation in PLV-infected cats. In this study, we evaluated viral infection and cytokine mRNA transcription in 12 different tissue reservoirs approximately five months post infection. We quantitated tissue proviral load, viral mRNA load and relative transcription of IL-10, IL-12p40 and IFNgamma from tissues of cats exposed to FIV, PLV or both viruses and analyzed these parameters using a multivariate statistical approach. The distribution and intensity of FIV infection and IFNgamma transcription differed between single and co-infected cats, characterized by higher FIV proviral loads and IFNgamma expression in co infected cat tissues. Variability in FIV mRNA load and IFNgamma was significantly more constrained in co-infected versus singly infected cat tissues. Single infected:co-infected ratios of FIV mRNA load compared to FIV proviral load indicated that active viral transcription was apparently inhibited during co infection. These results indicate that previous PLV infection increases activation of tissue innate immunity and constrains the ability of FIV to productively infect tissue reservoirs of infection for months, independent of FIV proviral load, supporting a model in which innate immunity and/or modulation of target cell susceptibility play a key role in PLV-induced protection from FIV disease. PMID- 22069522 TI - The hepatitis C virus glycan shield and evasion of the humoral immune response. AB - Despite the induction of effective immune responses, 80% of hepatitis C virus (HCV)-infected individuals progress from acute to chronic hepatitis. In contrast to the cellular immune response, the role of the humoral immune response in HCV clearance is still subject to debate. Indeed, HCV escapes neutralizing antibodies in chronically infected patients and reinfection has been described in human and chimpanzee. Studies of antibody-mediated HCV neutralization have long been hampered by the lack of cell-culture-derived virus and the absence of a small animal model. However, the development of surrogate models and recent progress in HCV propagation in vitro now enable robust neutralization assays to be performed. These advances are beginning to shed some light on the mechanisms of HCV neutralization. This review summarizes the current state of knowledge of the viral targets of anti-HCV-neutralizing antibodies and the mechanisms that enable HCV to evade the humoral immune response. The recent description of the HCV glycan shield that reduces the immunogenicity of envelope proteins and masks conserved neutralizing epitopes at their surface constitutes the major focus of this review. PMID- 22069523 TI - Viral ancestors of antiviral systems. AB - All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features. PMID- 22069524 TI - The molecular biology of frog virus 3 and other iridoviruses infecting cold blooded vertebrates. AB - Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicative- and virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease. PMID- 22069527 TI - A novel platform for research on toxins. PMID- 22069526 TI - Recombination in hepatitis C virus. AB - Hepatitis C virus (HCV) is a Flavivirus with a positive-sense, single-stranded RNA genome of about 9,600 nucleotides. It is a major cause of liver disease, infecting almost 200 million people all over the world. Similarly to most RNA viruses, HCV displays very high levels of genetic diversity which have been used to differentiate six major genotypes and about 80 subtypes. Although the different genotypes and subtypes share basic biological and pathogenic features they differ in clinical outcomes, response to treatment and epidemiology. The first HCV recombinant strain, in which different genome segments derived from parentals of different genotypes, was described in St. Petersburg (Russia) in 2002. Since then, there have been only a few more than a dozen reports including descriptions of HCV recombinants at all levels: between genotypes, between subtypes of the same genotype and even between strains of the same subtype. Here, we review the literature considering the reasons underlying the difficulties for unequivocally establishing recombination in this virus along with the analytical methods necessary to do it. Finally, we analyze the potential consequences, especially in clinical practice, of HCV recombination in light of the coming new therapeutic approaches against this virus. PMID- 22069525 TI - Cellular restriction factors of feline immunodeficiency virus. AB - Lentiviruses are known for their narrow cell- and species-tropisms, which are determined by cellular proteins whose absence or presence either support viral replication (dependency factors, cofactors) or inhibit viral replication (restriction factors). Similar to Human immunodeficiency virus type 1 (HIV-1), the cat lentivirus Feline immunodeficiency virus (FIV) is sensitive to recently discovered cellular restriction factors from non-host species that are able to stop viruses from replicating. Of particular importance are the cellular proteins APOBEC3, TRIM5alpha and tetherin/BST-2. In general, lentiviruses counteract or escape their species' own variant of the restriction factor, but are targeted by the orthologous proteins of distantly related species. Most of the knowledge regarding lentiviral restriction factors has been obtained in the HIV-1 system; however, much less is known about their effects on other lentiviruses. We describe here the molecular mechanisms that explain how FIV maintains its replication in feline cells, but is largely prevented from cross-species infections by cellular restriction factors. PMID- 22069528 TI - Effect of neem leaf extract and neem oil on Penicillium growth, sporulation, morphology and ochratoxin A production. AB - In vitro trials were conducted to evaluate the effect of Azadirachtaindica (neem) extracts on mycelial growth, sporulation, morphology and ochratoxin A production by P. verrucosum and P. brevicompactum. The effect of neem oil extract from seeds and leaf was evaluated at 0.125; 0.25 and 0.5% and 6.25 and 12.5 mg/mL, respectively, in Yeast Extract Sucrose (YES) medium. Ochratoxin A production was evaluated by a thin-layer chromatography technique. Oil extracts exhibited significant (p <= 0.05) reduction of growth and sporulation of the fungi. No inhibition of ochratoxin A production was observed. Given its accessibility and low cost, neem oil could be implemented as part of a sustainable integrated pest management strategy for plant disease, as it has been shown to be fungitoxic by inhibition of growth and sporulation. PMID- 22069529 TI - Intersex tilapia (Oreochromis spp.) from a contaminated river in Taiwan: A case study. AB - River pollution in Taiwan is rather serious, but so far there have been no reports of fish intersex problems. This report reveals that 50% male tilapia in the Era-Jiin River of southern Taiwan were found to be feminized in an October 8, 1994 collection from station EJ-2 of this river. After discounting all other possible causative factors, and correlating with endocrine disrupting chemicals found in this river, we suggest that there is a great possibility that the occurrence of intersex tilapia was caused by these chemicals. The above finding suggests that greater attention needs to be given to endocrine disrupting chemicals problems. PMID- 22069530 TI - Oxazolone-induced delayed type hypersensitivity reaction in the adult yucatan pigs. A useful model for drug development and validation. AB - The purpose of this study was to establish a model of delayed type hypersensitivity (DTH) reaction in the ear skin of large animals such as adult Yucatan pigs, which may aid in evaluating the efficacy of therapeutic modalities of newly developed anti-inflammatory drugs. The pigs were sensitized with oxazolone, re-challenged with the same irritant six days later, and dosed with either vehicle or with cyclosporine A (CsA) before and after challenge. CsA reduced the redness, inhibited the accumulation of ear fluid and inflammatory cells, as well as the release of the inflammatory mediators. Further, CsA inhibited the proliferation of T cells collected from the spleens or PBMCs of CsA treated pigs when these cells were stimulated in vitro with PMA plus Ionomycin. These results indicate that pig skin can be used to evaluate modalities for the purpose of developing drugs that may be used to treat DTH in humans. PMID- 22069531 TI - Predicted roles of the uncharacterized clustered genes in aflatoxin biosynthesis. AB - Biosynthesis of the toxic and carcinogenic aflatoxins (AFs) requires the activity of more than 27 enzymes. The roles in biosynthesis of newly described enzymes are discussed in this review. We suggest that HypC catalyzes the oxidation of norsolorinic acid anthrone; AvfA (AflI), the ring-closure step in formation of hydroxyversicolorone; HypB, the second oxidation step in conversion of O methylsterigmatocystin to AF; and HypE and NorA (AflE), the final two steps in AFB(1) formation. HypD, an integral membrane protein, affects fungal development and lowers AF production while AflJ (AflS), has a partial methyltransferase domain that may be important in its function as a transcriptional co-activator. PMID- 22069532 TI - Immune response to Chlamydophila abortus POMP91B protein in the context of different Pathogen Associated Molecular Patterns (PAMP); role of antigen in the orientation of immune response. AB - In a previous study, we used bacterial flagellin to deliver antigens such as p27 of Mycobacterium tuberculosis to a host immune system and obtained a potent Th1 response compared to those obtained with Freund's adjuvant and DNA immunization. In the current study, using a POMP91B antigen of Chlamydophila abortus, a human and animal pathogen, as a model, we found that this antigen is unable to promote Th1 response. However, this antigen, unlike others, was able to induce a good Th2 response and IL-4 production after immunization by recombinant protein in Freund's adjuvant or in phosphate buffered saline. Our results suggest that immune response is not only dependent on the immunization adjuvant, but also dependent on the nature of antigen used. PMID- 22069533 TI - Cyclopiazonic acid biosynthesis of Aspergillus flavus and Aspergillus oryzae. AB - Cyclopiazonic acid (CPA) is an indole-tetramic acid neurotoxin produced by some of the same strains of A. flavus that produce aflatoxins and by some Aspergillus oryzae strains. Despite its discovery 40 years ago, few reviews of its toxicity and biosynthesis have been reported. This review examines what is currently known about the toxicity of CPA to animals and humans, both by itself or in combination with other mycotoxins. The review also discusses CPA biosynthesis and the genetic diversity of CPA production in A. flavus/oryzae populations. PMID- 22069534 TI - Asp Viper (Vipera aspis) envenomation: experience of the Marseille Poison Centre from 1996 to 2008. AB - A retrospective case review study of viper envenomations collected by the Marseille's Poison Centre between 1996 and 2008 was performed. RESULTS: 174 cases were studied (52 grade 1 = G1, 90 G2 and 32 G3). G1 patients received symptomatic treatments (average hospital stay 0.96 day). One hundred and six (106) of the G2/G3 patients were treated with the antivenom Viperfav* (2.1+/-0.9 days in hospital), while 15 of them received symptomatic treatments only (plus one immediate death) (8.1+/-4 days in hospital, 2 of them died). The hospital stay was significantly reduced in the antivenom treated group (p < 0.001), and none of the 106 antivenom treated patients had immediate (anaphylaxis) or delayed (serum sickness) allergic reactions. CONCLUSION: Viperfav* antivenom was safe and effective for treating asp viper venom-induced toxicity. PMID- 22069535 TI - CyanoHAB occurrence and water irrigation cyanotoxin contamination: ecological impacts and potential health risks. AB - The world-wide occurrence of harmful cyanobacteria blooms "CyanoHAB" in fresh and brackish waters creates problems for all life forms. During CyanoHAB events, toxic cyanobacteria produce cyanotoxins at high levels that can cause chronic and sub-chronic toxicities to animals, plants and humans. Cyanotoxicity in eukaryotes has been mainly focused on animals, but during these last years, data, related to cyanotoxin (mainly microcystins, MCs) impact on both aquatic and terrestrials crop plants irrigated by water containing these toxins, have become more and more available. This last cited fact is gaining importance since plants could in a direct or indirect manner contribute to cyanotoxin transfer through the food chain, and thus constitute a potent health risk source. The use of this contaminated irrigation water can also have an economical impact which appears by a reduction of the germination rate of seeds, and alteration of the quality and the productivity of crop plants. The main objective of this work was to discuss the eventual phytotoxicity of cyanotoxins (microcystins) as the major agricultural impacts induced by the use of contaminated water for plant irrigation. These investigations confirm the harmful effects (ecological, eco physiological, socio-economical and sanitary risk) of dissolved MCs on agricultural plants. Thus, cyanotoxin phytotoxicity strongly suggests a need for the surveillance of CyanoHAB and the monitoring of water irrigation quality as well as for drinking water. PMID- 22069536 TI - Determination of the biological activity and structure activity relationships of drugs based on the highly cytotoxic duocarmycins and CC-1065. AB - The natural antibiotics CC-1065 and the duocarmycins are highly cytotoxic compounds which however are not suitable for cancer therapy due to their general toxicity. We have developed glycosidic prodrugs of seco-analogues of these antibiotics for a selective cancer therapy using conjugates of glycohydrolases and tumour-selective monoclonal antibodies for the liberation of the drugs from the prodrugs predominantly at the tumour site. For the determination of structure activity relationships of the different seco-drugs, experiments addressing their interaction with synthetic DNA were performed. Using electro-spray mass spectrometry and high performance liquid chromatography, the experiments revealed a correlation of the stability of these drugs with their cytotoxicity in cell culture investigations. Furthermore, it was shown that the drugs bind to AT-rich regions of double-stranded DNA and the more cytotoxic drugs induce DNA fragmentation at room temperature in several of the selected DNA double-strands. Finally, an explanation for the very high cytotoxicity of CC-1065, the duocarmycins and analogous drugs is given. PMID- 22069537 TI - Comparison of sea snake (Hydrophiidae) neurotoxin to cobra (Naja) neurotoxin. AB - Both sea snakes and cobras have venoms containing postsynaptic neurotoxins. Comparison of the primary structures indicates many similarities, especially the positions of the four disulfide bonds. However, detailed examination reveals differences in several amino acid residues. Amino acid sequences of sea snake neurotoxins were determined, and then compared to cobra neurotoxins by computer modeling. This allowed for easy comparison of the similarities and differences between the two types of postsynaptic neurotoxins. Comparison of computer models for the toxins of sea snakes and cobra will reveal the three dimensional difference of the toxins much clearer than the amino acid sequence alone. PMID- 22069538 TI - Isolation and chemical characterization of a toxin isolated from the venom of the sea snake, Hydrophis torquatus aagardi. AB - Sea snakes (family: Hydrophiidae) are serpents found in the coastal areas of the Indian and Pacific Oceans. There are two subfamilies in Hydrophiidae: Hydrophiinae and Laticaudinae. A toxin, aagardi toxin, was isolated from the venom of the Hydrophiinae snake, Hydrophis torquatus aagardi and its chemical properties such as molecular weight, isoelectric point, importance of disulfide bonds, lack of enzymatic activity and amino acid sequence were determined. The amino acid sequence indicated a close relationship to the primary structure of other Hydrophiinae toxins and a significant difference from Laticaudinae toxins, confirming that primary toxin structure is closely related to sea snake phylogenecity. PMID- 22069539 TI - Functional analysis of a putative Dothistromin toxin MFS transporter gene. AB - Dothistromin is a non-host selective toxin produced by the pine needle pathogen Dothistroma septosporum. Dothistromin is not required for pathogenicity, but may have a role in competition and niche protection. To determine how D. septosporum tolerates its own toxin, a putative dothistromin transporter, dotC, was investigated. Studies with mutants lacking a functional dotC gene, overproducing dotC, or with a dotC-GFP fusion gene, did not provide conclusive evidence of a role in dothistromin efflux. The mutants revealed a major effect of dotC on dothistromin biosynthesis but were resistant to exogenous dothistromin. Intracellular localization studies suggest that compartmentalization may be important for dothistromin tolerance. PMID- 22069540 TI - Preparation of an in-house reference material containing fumonisins in Thai rice and matrix extension of the analytical method for Japanese rice. AB - Mycotoxin contamination in rice is less reported, compared to that in wheat or maize, however, some Fusarium fungi occasionally infect rice in the paddy field. Fumonisins are mycotoxins mainly produced by Fusarium verticillioides, which often ruins maize. Rice adherent fungus Gibberella fujikuroi is taxonomically near to F. verticillioides, and there are sporadic reports of fumonisin contamination in rice from Asia, Europe and the United States. Therefore, there exists the potential risk of fumonisin contamination in rice as well as the need for the validated analytical method for fumonisins in rice. Although both natural and spiked reference materials are available for some Fusarium mycotoxins in matrices of wheat and maize, there are no reference materials for Fusarium mycotoxins in rice. In this study, we have developed a method for the preparation of a reference material containing fumonisins in Thai rice. A ShakeMaster grinding machine was used for the preparation of a mixed material of blank Thai rice and F. verticillioides-infected Thai rice. The homogeneity of the mixed material was confirmed by one-way analysis of variance, which led this material to serve as an in-house reference material. Using this reference material, several procedures to extract fumonisins from Thai rice were compared. Accordingly, we proved the applicability of an effective extraction procedure for the determination of fumonisins in Japanese rice. PMID- 22069541 TI - Fluorescence polarization immunoassay of mycotoxins: a review. AB - Immunoassays are routinely used in the screening of commodities and foods for fungal toxins (mycotoxins). Demands to increase speed and lower costs have lead to continued improvements in such assays. Because many reported mycotoxins are low molecular weight (below 1 kDa), immunoassays for their detection have generally been constructed in competitive heterogeneous formats. An exception is fluorescence polarization immunoassay (FPIA), a homogeneous format that does not require the separation of bound and free labels (tracer). The potential for rapid, solution phase, immunoassays has been realized in the development of FPIA for many of the major groups of mycotoxins, including aflatoxins, fumonisins, group B trichothecenes (primarily deoxynivalenol), ochratoxin A, and zearalenone. This review describes the basic principles of FPIA and summarizes recent research in this area with regard to mycotoxins. PMID- 22069542 TI - Clostridium perfringens iota-toxin: structure and function. AB - Clostridium perfringens iota-toxin is composed of the enzyme component (Ia) and the binding component (Ib). Ib binds to receptor on targeted cells and translocates Ia into the cytosol of the cells. Ia ADP-ribosylates actin, resulting in cell rounding and death. Comparisons of the deduced amino acid sequence from the gene and three-dimensional structure of Ia with those of ADP ribosylating toxins (ARTs) suggests that there is striking structural similarity among these toxins. Our objectives are to review the recent advances in the character, structure-function, and the mode of action of iota-toxin by consideration of the findings about ARTs. PMID- 22069543 TI - Protein Domain Analysis of C. botulinum Type A Neurotoxin and Its Relationship with Other Botulinum Serotypes. AB - Botulinum neurotoxins (BoNTs) are highly potent poisons produced by seven serotypes of Clostridium botulinum. The mechanism of neurotoxin action is a multistep process which leads to the cleavage of one of three different SNARE proteins essential for synaptic vesicle fusion and transmission of the nerve signals to muscles: synaptobrevin, syntaxin, or SNAP-25. In order to understand the precise mechanism of neurotoxin in a host, the domain structure of the neurotoxin was analyzed among different serotypes of C. botulinum. The results indicate that neurotoxins type A, C, D, E and F contain a coiled-coil domain while types B and type G neurotoxin do not. Interestingly, phylogenetic analysis based on neurotoxin sequences has further confirmed that serotypes B and G are closely related. These results suggest that neurotoxin has multi-domain structure, and coiled-coil domain plays an important role in oligomerisation of the neurotoxin. Domain analysis may help to identify effective antibodies to treat Botulinum toxin intoxication. PMID- 22069544 TI - Structure and function of snake venom proteins affecting platelet plug formation. AB - Many snake venom proteins have been isolated that affect platelet plug formation by interacting either with platelet integrins, membrane glycoprotein Ib (GPIb), or plasma von Willebrand factor (VWF). Among them, disintegrins purified from various snake venoms are strong inhibitors of platelet aggregation. Botrocetin and bitiscetin derived from Bothrops jararaca and Bitis arietans venom, respectively, induce VWF-dependent platelet agglutination in vitro. Several GPIb binding proteins have also been isolated from snake venoms. In this review, we focus on the structure and function of those snake venom proteins that influence platelet plug formation. These proteins are potentially useful as reagents for the sub-diagnosis of platelet disorder or von Willebrand disease, as well as for clinical and basic research of thrombosis and hemostasis. PMID- 22069545 TI - Sensing the deadliest toxin: technologies for botulinum neurotoxin detection. AB - Sensitive and rapid detection of botulinum neurotoxins (BoNTs), the most poisonous substances known to date, is essential for studies of medical applications of BoNTs and detection of poisoned food, as well as for response to potential bioterrorist threats. Currently, the most common method of BoNT detection is the mouse bioassay. While this assay is sensitive, it is slow, quite expensive, has limited throughput and requires sacrificing animals. Herein, we discuss and compare recently developed alternative in vitro detection methods and assess their ability to supplement or replace the mouse bioassay in the analysis of complex matrix samples. PMID- 22069546 TI - Reciprocal interactions between lactoferrin and bacterial endotoxins and their role in the regulation of the immune response. AB - Lactoferrin (Lf), an iron-binding glycoprotein expressed in most biological fluids, represents a major component of the mammalian innate immune system. Lf's multiple activities rely not only on its capacity to bind iron, but also to interact with molecular and cellular components of both host and pathogens. Lf can bind and sequester lipopolysaccharide (LPS), thus preventing pro-inflammatory pathway activation, sepsis and tissue damage. However, Lf-bound LPS may retain the capacity to induce cell activation via Toll-like receptor 4-dependent and independent mechanisms. This review discusses the complex interplay between Lf and LPS and its relevance in the regulation of the immune response. PMID- 22069549 TI - Calprotectin (S100A8/S100A9) and myeloperoxidase: co-regulators of formation of reactive oxygen species. AB - INFLAMMATORY MEDIATORS TRIGGER POLYMORPHONUCLEAR NEUTROPHILS (PMN) TO PRODUCE REACTIVE OXYGEN SPECIES (ROS: O(2) (-), H(2)O(2), ?OH). Mediated by myeloperoxidase in PMN, HOCl is formed, detectable in a chemiluminescence (CL) assay. We have shown that the abundant cytosolic PMN protein calprotectin (S100A8/A9) similarly elicits CL in response to H(2)O(2) in a cell-free system. Myeloperoxidase and calprotectin worked synergistically. Calprotectin-induced CL increased, whereas myeloperoxidase-triggered CL decreased with pH > 7.5. Myeloperoxidase needed NaCl for CL, calprotectin did not. 4-hydroxybenzoic acid, binding ?OH, almost abrogated calprotectin CL, but moderately increased myeloperoxidase activity. The combination of native calprotectin, or recombinant S100A8/A9 proteins, with NaOCl markedly enhanced CL. NaOCl may be the synergistic link between myeloperoxidase and calprotectin. Surprisingly- and unexplained- at higher concentration of S100A9 the stimulation vanished, suggesting a switch from pro-oxidant to anti-oxidant function. We propose that the ?OH is predominant in ROS production by calprotectin, a function not described before. PMID- 22069547 TI - the versatility of the Helicobacter pylori vacuolating cytotoxin vacA in signal transduction and molecular crosstalk. AB - By modulating important properties of eukaryotic cells, many bacterial protein toxins highjack host signalling pathways to create a suitable niche for the pathogen to colonize and persist. Helicobacter pylori VacA is paradigm of pore forming toxins which contributes to the pathogenesis of peptic ulceration. Several cellular receptors have been described for VacA, which exert different effects on epithelial and immune cells. The crystal structure of VacA p55 subunit might be important for elucidating details of receptor interaction and pore formation. Here we discuss the multiple signalling activities of this important toxin and the molecular crosstalk between VacA and other virulence factors. PMID- 22069550 TI - Cytotoxic Necrotizing Factors (CNFs)-A Growing Toxin Family. AB - The Escherichia coli Cytotoxic Necrotizing Factors, CNF1, CNF2, CNF3 and CNFY from Yersinia pseudotuberculosis belong to a family of deamidating toxins. CNFs deamidate glutamine 63/61 in the switch II region of Rho GTPases that is essential for GTP hydrolysing activity. Deamidation leads to constitutive activation of Rho GTPases. However, cellular mechanisms like proteasomal degradation of the activated Rho proteins restrict the action of the GTPases. This review describes the differences between the toxin family members concerning expression, cellular entry and substrate specificity. PMID- 22069552 TI - Bothrops lanceolatus bites: guidelines for severity assessment and emergent management. AB - Approximately 20-30 declared snakebite cases occurin Martinique each year. Bothrops lanceolatus, a member of the Crotalidae family, is considered to be the only involved snake. B. lanceolatus, commonly named "Fer-de-Lance", is endemic and only found on this Caribbean island. Envenomation local features include the presence of fang marks, swelling, pain, bleeding from punctures, and ecchymosis. Severe envenomation is associated with multiple systemic thromboses appearing within 48 h of the bite and resulting in cerebral, myocardial or pulmonary infarctions. Diagnosis requires first of all identification of the snake. Coagulation tests are helpful to identify thrombocytopenia or disseminated intravascular coagulation. A clinical score based on 4 grades is helpful to assess envonimation severity. A specific monovalent equine anti-venom (Bothrofav((r)), Sanofi-Pasteur, France) to neutralize B. lanceolatus venom is available. Its early administration within 6h from the biting in case of progressive local injures, general signs or coagulation disturbances is effective to prevent severe thrombosis and coagulopathy. Its tolerance is considered to be good. Despite an increasing incidence of bites, no deaths have been recently attributed to B. lanceolatus in Martinique, probably due to the currently recommended strategy of early antivenom administration when required. PMID- 22069554 TI - PP2A inhibition assay using recombinant enzyme for rapid detection of okadaic acid and its analogs in shellfish. AB - Okadaic acid and its analogs (OAs) responsible for diarrhetic shellfish poisoning (DSP) strongly inhibit protein phosphatase 2A (PP2A) and thus are quantifiable by measuring the extent of the enzyme inhibition. In this study, we evaluated the suitability of the catalytic subunit of recombinant human PP2A (rhPP2Ac) for use in a microplate OA assay. OA, dinophysistoxin-1(DTX1), and hydrolyzate of 7-O palmitoyl-OA strongly inhibited rhPP2Ac activity with IC(50) values of 0.095, 0.104, and 0.135 nM, respectively. The limits of detection and quantitation for OA in the digestive gland of scallops and mussels were 0.0348 MUg/g and 0.0611 MUg/g respectively, and, when converted to the whole meat basis, are well below the regulation level proposed by EU (0.16 MUg/g whole meat). A good correlation with LC-MS data was demonstrated, the correlation coefficient being 0.996 with the regression slope of 1.097. PMID- 22069553 TI - The protein kinase C agonist PEP005 (ingenol 3-angelate) in the treatment of human cancer: a balance between efficacy and toxicity. AB - The diterpene ester ingenol-3-angelate (referred to as PEP005) is derived from the plant Euphorbia peplus. Crude euphorbia extract causes local toxicity and transient inflammation when applied topically and has been used in the treatment of warts, skin keratoses and skin cancer. PEP005 is a broad range activator of the classical (alpha, beta, gamma) and novel (delta, epsilon, eta, theta) protein kinase C isoenzymes. Direct pro-apoptotic effects of this drug have been demonstrated in several malignant cells, including melanoma cell lines and primary human acute myelogenous leukemia cells. At micromolar concentrations required to kill melanoma cells this agent causes PKC-independent secondary necrosis. In contrast, the killing of leukemic cells occurs in the nanomolar range, requires activation of protein kinase C delta (PKCdelta) and is specifically associated with translocation of PKCdelta from the cytoplasm to the nuclear membrane. However, in addition to this pro-apoptotic effect the agent seems to have immunostimulatory effects, including: (i) increased chemokine release by malignant cells; (ii) a general increase in proliferation and cytokine release by activated T cells, including T cells derived from patients with chemotherapy-induced lymphopenia; (iii) local infiltration of neutrophils after topical application with increased antibody-dependent cytotoxicity; and (iv) development of specific anti-cancer immune responses by CD8(+) T cells in animal models. Published studies mainly describe effects from in vitro investigations or after topical application of the agent, and careful evaluation of the toxicity after systemic administration is required before the possible use of this agent in the treatment of malignancies other than skin cancers. PMID- 22069551 TI - Curcumin-the paradigm of a multi-target natural compound with applications in cancer prevention and treatment. AB - As cancer is a multifactor disease, it may require treatment with compounds able to target multiple intracellular components. We summarize here how curcumin is able to modulate many components of intracellular signaling pathways implicated in inflammation, cell proliferation and invasion and to induce genetic modulations eventually leading to tumor cell death. Clinical applications of this natural compound were initially limited by its low solubility and bioavailability in both plasma and tissues but combination with adjuvant and delivery vehicles was reported to largely improve bio-availability of curcumin. Moreover, curcumin was reported to act in synergism with several natural compounds or synthetic agents commonly used in chemotherapy. Based on this, curcumin could thus be considered as a good candidate for cancer prevention and treatment when used alone or in combination with other conventional treatments. PMID- 22069555 TI - Comments on "Ochratoxin A: In utero Exposure in Mice Induces Adducts in Testicular DNA. Toxins 2010, 2, 1428-1444"-Mis-Citation of Rat Literature to Justify a Hypothetical Role for Ochratoxin A in Testicular Cancer. AB - A manuscript in the journal recently cited experimental rat data from two manuscripts to support plausibility of a thesis that ochratoxin A might be a cause of human testicular cancer. I believe that there is no experimental evidence that ochratoxin A produces testicular cancer in rats or mice. PMID- 22069557 TI - Genomic damage in endstage renal disease-contribution of uremic toxins. AB - Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-alpha. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation. PMID- 22069558 TI - Diversity and impact of prokaryotic toxins on aquatic environments: a review. AB - Microorganisms are ubiquitous in all habitats and are recognized by their metabolic versatility and ability to produce many bioactive compounds, including toxins. Some of the most common toxins present in water are produced by several cyanobacterial species. As a result, their blooms create major threats to animal and human health, tourism, recreation and aquaculture. Quite a few cyanobacterial toxins have been described, including hepatotoxins, neurotoxins, cytotoxins and dermatotoxins. These toxins are secondary metabolites, presenting a vast diversity of structures and variants. Most of cyanobacterial secondary metabolites are peptides or have peptidic substructures and are assumed to be synthesized by non-ribosomal peptide synthesis (NRPS), involving peptide synthetases, or NRPS/PKS, involving peptide synthetases and polyketide synthases hybrid pathways. Besides cyanobacteria, other bacteria associated with aquatic environments are recognized as significant toxin producers, representing important issues in food safety, public health, and human and animal well being. Vibrio species are one of the most representative groups of aquatic toxin producers, commonly associated with seafood-born infections. Some enterotoxins and hemolysins have been identified as fundamental for V. cholerae and V. vulnificus pathogenesis, but there is evidence for the existence of other potential toxins. Campylobacter spp. and Escherichia coli are also water contaminants and are able to produce important toxins after infecting their hosts. Other bacteria associated with aquatic environments are emerging as toxin producers, namely Legionella pneumophila and Aeromonas hydrophila, described as responsible for the synthesis of several exotoxins, enterotoxins and cytotoxins. Furthermore, several Clostridium species can produce potent neurotoxins. Although not considered aquatic microorganisms, they are ubiquitous in the environment and can easily contaminate drinking and irrigation water. Clostridium members are also spore-forming bacteria and can persist in hostile environmental conditions for long periods of time, contributing to their hazard grade. Similarly, Pseudomonas species are widespread in the environment. Since P. aeruginosa is an emergent opportunistic pathogen, its toxins may represent new hazards for humans and animals. This review presents an overview of the diversity of toxins produced by prokaryotic microorganisms associated with aquatic habitats and their impact on environment, life and health of humans and other animals. Moreover, important issues like the availability of these toxins in the environment, contamination sources and pathways, genes involved in their biosynthesis and molecular mechanisms of some representative toxins are also discussed. PMID- 22069559 TI - ADAM-15 disintegrin-like domain structure and function. AB - The ADAM (a disintegrin-like and metalloproteinase) proteins are a family of transmembrane cell-surface proteins with important functions in adhesion and proteolytic processing in all animals. Human ADAM-15 is the only member of the ADAM family with the integrin binding motif Arg-Gly-Asp (RGD) in its disintegrin like domain. This motif is also found in most snake venom disintegrins and other disintegrin-like proteins. This unique RGD motif within ADAM-15 serves as an integrin ligand binding site, through which it plays a pivotal role in interacting with integrin receptors, a large family of heterodimeric transmembrane glycoproteins. This manuscript will present a review of the RGD containing disintegrin-like domain structures and the structural features responsible for their activity as antagonists of integrin function in relation to the canonical RGD template. PMID- 22069561 TI - Verotoxin-1 treatment or manipulation of its receptor globotriaosylceramide (gb3) for reversal of multidrug resistance to cancer chemotherapy. AB - A major problem with anti-cancer drug treatment is the development of acquired multidrug resistance (MDR) of the tumor cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the globotriaosylceramide membrane receptor (Gb3), a glycolipid associated with multidrug resistance. Gb3 is overexpressed in many human tumors and tumor cell lines with inherent or acquired MDR. Gb3 is co expressed and interplays with the membrane efflux transporter P-gp encoded by the MDR1 gene. P-gp could act as a lipid flippase and stimulate Gb3 induction when tumor cells are exposed to cancer chemotherapy. Recent work has shown that apoptosis and inherent or acquired multidrug resistance in Gb3-expressing tumors could be affected by VT-1 holotoxin, a sub-toxic concentration of the holotoxin concomitant with chemotherapy or its Gb3-binding B-subunit coupled to cytotoxic or immunomodulatory drug, as well as chemical manipulation of Gb3 expression. The interplay between Gb3 and P-gp thus gives a possible physiological approach to augment the chemotherapeutic effect in multidrug resistant tumors. PMID- 22069562 TI - Biological and pathological studies of rosmarinic acid as an inhibitor of hemorrhagic Trimeresurus flavoviridis (habu) venom. AB - In our previous report, rosmarinic acid (RA) was revealed to be an antidote active compound in Argusia argentea (family: Boraginaceae). The plant is locally used in Okinawa in Japan as an antidote for poisoning from snake venom, Trimeresurus flavoviridis (habu). This article presents mechanistic evidence of RA's neutralization of the hemorrhagic effects of snake venom. Anti-hemorrhagic activity was assayed by using several kinds of snake venom. Inhibition against fibrinogen hydrolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. A histopathological study was done by microscopy after administration of venom in the presence or absence of RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, RA inhibited both hemorrhage and neutrophil infiltrations caused by T. flavoviridis venom in pathology sections. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability. PMID- 22069560 TI - Targeting inflammatory pathways by triterpenoids for prevention and treatment of cancer. AB - Traditional medicine and diet has served mankind through the ages for prevention and treatment of most chronic diseases. Mounting evidence suggests that chronic inflammation mediates most chronic diseases, including cancer. More than other transcription factors, nuclear factor-kappaB (NF-kappaB) and STAT3 have emerged as major regulators of inflammation, cellular transformation, and tumor cell survival, proliferation, invasion, angiogenesis, and metastasis. Thus, agents that can inhibit NF-kappaB and STAT3 activation pathways have the potential to both prevent and treat cancer. In this review, we examine the potential of one group of compounds called triterpenes, derived from traditional medicine and diet for their ability to suppress inflammatory pathways linked to tumorigenesis. These triterpenes include avicins, betulinic acid, boswellic acid, celastrol, diosgenin, madecassic acid, maslinic acid, momordin, saikosaponins, platycodon, pristimerin, ursolic acid, and withanolide. This review thus supports the famous adage of Hippocrates, "Let food be thy medicine and medicine be thy food". PMID- 22069565 TI - Warfarin toxicity and individual variability-clinical case. AB - Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives-superwarfarin anticoagulants-such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases. PMID- 22069563 TI - Mechanisms of Cisplatin nephrotoxicity. AB - Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. One of the limiting side effects of cisplatin use is nephrotoxicity. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatin-induced renal cell death. It has also become apparent that inflammation provoked by injury to renal epithelial cells serves to amplify kidney injury and dysfunction in vivo. This review summarizes recent advances in our understanding of cisplatin nephrotoxicity and discusses how these advances might lead to more effective prevention. PMID- 22069566 TI - Ecophysiology of Aspergillus section nigri species potential ochratoxin a producers. AB - After aflatoxins, ochratoxin A (OTA) is the most studied mycotoxin due to the toxicological significance in human and animal diets. OTA presence has been extensively reported worldwide in the last decade in several agricultural products. The main OTA producer in tropical and temperate climates is Aspergillus carbonarius followed by species belonging to A. niger aggregate. Currently, many scientists worldwide have studied the influence of water activity and temperature for growth and biosynthesis of OTA by these species on synthetic media. This article reviews ecophysiological studies of Aspergillus section Nigri strains on synthetic media and natural substrates. The results of these investigations suggest that significant amounts of OTA can be produced in only five days and that the use of different storage practices, such as a(W) and temperature levels below 0.930 and 15 degrees C, respectively, allow controlling fungal contamination and minimizing the OTA production in several products as peanuts, corn, dried grapes and derived products for human consumption. PMID- 22069567 TI - Snake venom disintegrins and cell migration. AB - Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin binding proteins such as the snake venom disintegrins that inhibit integrin mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion. PMID- 22069568 TI - Tetanus toxin C-fragment: the courier and the cure? AB - In many neurological disorders strategies for a specific delivery of a biological activity from the periphery to the central nervous system (CNS) remains a considerable challenge for successful therapy. Reporter assays have established that the non-toxic C-fragment of tetanus toxin (TTC), provided either as protein or encoded by non-viral naked DNA plasmid, binds pre-synaptic motor neuron terminals and can facilitate the retrograde axonal transport of desired therapeutic molecules to the CNS. Alleviated symptoms in animal models of neurological diseases upon delivery of therapeutic molecules offer a hopeful prospect for TTC therapy. This review focuses on what has been learned on TTC mediated neuronal targeting, and discusses the recent discovery that, instead of being merely a carrier molecule, TTC itself may well harbor neuroprotective properties. PMID- 22069569 TI - Targeted toxins in brain tumor therapy. AB - Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins. PMID- 22069570 TI - beta-N-methylamino-L-alanine induces neurological deficits and shortened life span in Drosophila. AB - The neurotoxic non-protein amino acid, beta-N-methylamino-L-alanine (BMAA), was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam. Recently, BMAA has been implicated as a fierce environmental factor that contributes to the etiology of Alzheimer's and Parkinson's diseases, in addition to ALS. However, the toxicity of BMAA in vivo has not been clearly demonstrated. Here we report our investigation of the neurotoxicity of BMAA in Drosophila. We found that dietary intake of BMAA reduced life span, locomotor functions, and learning and memory abilities in flies. The severity of the alterations in phenotype is correlated with the concentration of BMAA detected in flies. Interestingly, developmental exposure to BMAA had limited impact on survival rate, but reduced fertility in females, and caused delayed neurological impairment in aged adults. Our studies indicate that BMAA exposure causes chronic neurotoxicity, and that Drosophila serves as a useful model in dissecting the pathogenesis of ALS/PDC. PMID- 22069564 TI - Toxin-based therapeutic approaches. AB - Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID- 22069571 TI - Genetics of dothistromin biosynthesis of Dothistroma septosporum: an update. AB - Dothistroma needle blight is one of the most devastating fungal pine diseases worldwide. The disease is characterized by accumulation in pine needles of a red toxin, dothistromin, that is chemically related to aflatoxin (AF) and sterigmatocystin (ST). This review updates current knowledge of the genetics of dothistromin biosynthesis by the Dothistroma septosporum pathogen and highlights differences in gene organization and regulation that have been discovered between the dothistromin and AF/ST systems. Some previously reported genes are promoted or demoted as 'dothistromin genes' based on recent research. A new dothistromin gene, norB, is reported, and evidence of dothistromin gene homologs in other Dothideomycete fungi is presented. A hypothesis for the biological role of dothistromin is outlined. Finally, the impact that the availability of the D. septosporum genome sequence will have on dothistromin research is discussed. PMID- 22069573 TI - Genetics of dothistromin biosynthesis in the peanut pathogen Passalora arachidicola. AB - The peanut leaf spot pathogen Passalora arachidicola (Mycosphaerella arachidis) is known to produce dothistromin, a mycotoxin related to aflatoxin. This is a feature shared with the pine needle pathogen Dothistroma septosporum (Mycosphaerella pini). Dothistromin biosynthesis in D. septosporum commences at an unusually early stage of growth in culture compared to most other fungal secondary metabolites, and the biosynthetic genes are arranged in fragmented groups, in contrast to aflatoxin gene clusters. Dothistromin biosynthetic genes were identified and studied in P. arachidicola to determine if the attributes described in D. septosporum are shared by another dothistromin-producing species within the Class Dothideomycetes. It was shown that dothistromin biosynthesis is very similar in the two species with regard to gene sequence and gene synteny. Functional complementation of D. septosporum mutants with P. arachidicola dothistromin genes was also possible. These similarities support a vertical mode of dothistromin gene transmission. P. arachidicola also produced dothistromin at an early growth stage in culture, suggesting that this type of regulation pattern may be relevant to the biological role of dothistromin. PMID- 22069572 TI - Ribosome-inactivating proteins: from plant defense to tumor attack. AB - Ribosome-inactivating proteins (RIPs) are EC3.2.32.22 N-glycosidases that recognize a universally conserved stem-loop structure in 23S/25S/28S rRNA, depurinating a single adenine (A4324 in rat) and irreversibly blocking protein translation, leading finally to cell death of intoxicated mammalian cells. Ricin, the plant RIP prototype that comprises a catalytic A subunit linked to a galactose-binding lectin B subunit to allow cell surface binding and toxin entry in most mammalian cells, shows a potency in the picomolar range. The most promising way to exploit plant RIPs as weapons against cancer cells is either by designing molecules in which the toxic domains are linked to selective tumor targeting domains or directly delivered as suicide genes for cancer gene therapy. Here, we will provide a comprehensive picture of plant RIPs and discuss successful designs and features of chimeric molecules having therapeutic potential. PMID- 22069574 TI - Novel cytotoxic vectors based on adeno-associated virus. AB - Vectors based on adeno-associated virus (AAV) are promising tools for gene therapy. The production of strongly toxic vectors, for example for cancer directed gene transfer, is often unfeasible due to uncontrolled expression of toxic genes in vector-producing cells. Using an approach based on transcriptional repression, we have created novel AAV vectors carrying the genes coding for diphtheria toxin A (DTA) and the pro-apoptotic PUMA protein. The DTA vector had a significant toxic effect on a panel of tumor cell lines, and abrogation of protein synthesis could be shown. The PUMA vector had a toxic effect on HeLa and RPMI 8226 cells, and sensitized transduced cells to doxorubicin. To permit targeted gene transfer, we incorporated the DTA gene into a genetically modified AAV-2 capsid previously developed by our group that mediates enhanced transduction of murine breast cancer cells in vitro. This vector had a stronger cytotoxic effect on breast cancer cells than DTA vectors with wildtype AAV capsid or vectors with a random capsid modification. The vector production and application system presented here allows for easy exchange of promotors, transgenes and capsid specificity for certain target cells. It will therefore be of great possible value in a broad range of applications in cytotoxic gene therapy and significantly broadens the spectrum of available tools for AAV-based gene therapy. PMID- 22069576 TI - Occurrence of Fusarium spp. and fumonisins in stored wheat grains marketed in Iran. AB - Wheat grains are well known to be invaded by Fusarium spp. under field and storage conditions and contaminated with fumonisins. Therefore, determining Fusarium spp. and fumonisins in wheat grains is of prime importance to develop suitable management strategies and to minimize risk. Eighty-two stored wheat samples produced in Iran were collected from various supermarkets and tested for the presence of Fusarium spp. by agar plate assay and fumonisins by HPLC. A total of 386 Fusarium strains were isolated and identified through morphological characteristics. All these strains belonged to F. culmorum, F. graminearum, F. proliferatum and F.verticillioides. Of the Fusarium species, F. graminearum was the most prevalent species, followed by F. verticillioides, F. proliferatum and then F. culmorum. Natural occurrence of fumonisin B1 (FB1) could be detected in 56 (68.2%) samples ranging from 15-155 MUg/kg, fumonisin B2 (FB2) in 35 (42.6%) samples ranging from 12-86 MUg/kg and fumonisin B3 (FB3) in 26 (31.7%) samples ranging from 13-64 MUg/kg. The highest FB1 levels were detected in samples from Eilam (up to 155 MUg/kg) and FB2 and FB3 in samples from Gilan Gharb (up to 86 MUg/kg and 64 MUg/kg). PMID- 22069575 TI - Targeted secretion inhibitors-innovative protein therapeutics. AB - Botulinum neurotoxins are highly effective therapeutic products. Their therapeutic success results from highly specific and potent inhibition of neurotransmitter release with a duration of action measured in months. These same properties, however, make the botulinum neurotoxins the most potent acute lethal toxins known. Their toxicity and restricted target cell activity severely limits their clinical utility. Understanding the structure-function relationship of the neurotoxins has enabled the development of recombinant proteins selectively incorporating specific aspects of their pharmacology. The resulting proteins are not neurotoxins, but a new class of biopharmaceuticals, Targeted Secretion Inhibitors (TSI), suitable for the treatment of a wide range of diseases where secretion plays a major role. TSI proteins inhibit secretion for a prolonged period following a single application, making them particularly suited to the treatment of chronic diseases. A TSI for the treatment of chronic pain is in clinical development. PMID- 22069577 TI - Gangliosides block Aggregatibacter Actinomycetemcomitans leukotoxin (LtxA) mediated hemolysis. AB - Aggregatibacter actinomycetemcomitans is an oral pathogen and etiologic agent of localized aggressive periodontitis. The bacterium is also a cardiovascular pathogen causing infective endocarditis. A. actinomycetemcomitans produces leukotoxin (LtxA), an important virulence factor that targets white blood cells (WBCs) and plays a role in immune evasion during disease. The functional receptor for LtxA on WBCs is leukocyte function antigen-1 (LFA-1), a beta-2 integrin that is modified with N-linked carbohydrates. Interaction between toxin and receptor leads to cell death. We recently discovered that LtxA can also lyse red blood cells (RBCs) and hemolysis may be important for pathogenesis of A. actinomycetemcomitans. In this study, we further investigated how LtxA might recognize and lyse RBCs. We found that, in contrast to a related toxin, E. coli alpha-hemolysin, LtxA does not recognize glycophorin on RBCs. However, gangliosides were able to completely block LtxA-mediated hemolysis. Furthermore, LtxA did not show a preference for any individual ganglioside. LtxA also bound to ganglioside-rich C6 rat glioma cells, but did not kill them. Interaction between LtxA and C6 cells could be blocked by gangliosides with no apparent specificity. Gangliosides were only partially effective at preventing LtxA-mediated cytotoxicity of WBCs, and the effect was only observed when a high ratio of ganglioside:LtxA was used over a short incubation period. Based on the results presented here, we suggest that because of the similarity between N-linked sugars on LFA-1 and the structures of gangliosides, LtxA may have acquired the ability to lyse RBCs. PMID- 22069578 TI - The cyanobacteria derived toxin Beta-N-methylamino-L-alanine and amyotrophic lateral sclerosis. AB - There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis). The non-protein amino acid beta-N-methylamino-L-alanine (BMAA) was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer's disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin. PMID- 22069579 TI - Spider-venom peptides as therapeutics. AB - Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction. PMID- 22069580 TI - Strategy for treating motor neuron diseases using a fusion protein of botulinum toxin binding domain and streptavidin for viral vector access: work in progress. AB - Although advances in understanding of the pathogenesis of amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) have suggested attractive treatment strategies, delivery of agents to motor neurons embedded within the spinal cord is problematic. We have designed a strategy based on the specificity of botulinum toxin, to direct entry of viral vectors carrying candidate therapeutic genes into motor neurons. We have engineered and expressed fusion proteins consisting of the binding domain of botulinum toxin type A fused to streptavidin (SAv). This fusion protein will direct biotinylated viral vectors carrying therapeutic genes into motor nerve terminals where they can enter the acidified endosomal compartments, be released and undergo retrograde transport, to deliver the genes to motor neurons. Both ends of the fusion proteins are shown to be functionally intact. The binding domain end binds to mammalian nerve terminals at neuromuscular junctions, ganglioside GT1b (a target of botulinum toxin), and a variety of neuronal cells including primary chick embryo motor neurons, N2A neuroblastoma cells, NG108-15 cells, but not to NG CR72 cells, which lack complex gangliosides. The streptavidin end binds to biotin, and to a biotinylated Alexa 488 fluorescent tag. Further studies are in progress to evaluate the delivery of genes to motor neurons in vivo, by the use of biotinylated viral vectors. PMID- 22069582 TI - Pasteurella multocida toxin activates various heterotrimeric G proteins by deamidation. AB - Pasteurella multocida produces a 146-kDa protein toxin (Pasteurella multocida toxin, PMT), which stimulates diverse cellular signal transduction pathways by activating heterotrimeric G proteins. PMT deamidates a conserved glutamine residue of the alpha-subunit of heterotrimeric G proteins that is essential for GTP-hydrolysis, thereby arresting the G protein in the active state. The toxin substrates are Galpha(q) Galpha(13) and the Galpha(i)-family proteins. Activation of these alpha-subunits causes stimulation of phospholipase Cbeta, Rho-guanine nucleotide exchange factors or inhibition of adenylyl cyclase. This article provides the current knowledge on PMT concerning the structure-function analysis based on the crystal structure and recently elucidated molecular mode of action. Furthermore, the impact of PMT on cellular signaling is discussed. PMID- 22069581 TI - Botulinum neurotoxin for pain management: insights from animal models. AB - The action of botulinum neurotoxins (BoNTs) at the neuromuscular junction has been extensively investigated and knowledge gained in this field laid the foundation for the use of BoNTs in human pathologies characterized by excessive muscle contractions. Although much more is known about the action of BoNTs on the peripheral system, growing evidence has demonstrated several effects also at the central level. Pain conditions, with special regard to neuropathic and intractable pain, are some of the pathological states that have been recently treated with BoNTs with beneficial effects. The knowledge of the action and potentiality of BoNTs utilization against pain, with emphasis for its possible use in modulation and alleviation of chronic pain, still represents an outstanding challenge for experimental research. This review highlights recent findings on the effects of BoNTs in animal pain models. PMID- 22069583 TI - Animal Toxins: How is Complexity Represented in Databases? AB - Peptide toxins synthesized by venomous animals have been extensively studied in the last decades. To be useful to the scientific community, this knowledge has been stored, annotated and made easy to retrieve by several databases. The aim of this article is to present what type of information users can access from each database. ArachnoServer and ConoServer focus on spider toxins and cone snail toxins, respectively. UniProtKB, a generalist protein knowledgebase, has an animal toxin-dedicated annotation program that includes toxins from all venomous animals. Finally, the ATDB metadatabase compiles data and annotations from other databases and provides toxin ontology. PMID- 22069584 TI - Escherichia coli cytotoxic necrotizing factor 1 (CNF1): toxin biology, in vivo applications and therapeutic potential. AB - CNF1 is a protein toxin produced by certain pathogenic strains of Escherichia coli. It permanently activates the regulatory Rho, Rac, and Cdc42 GTPases in eukaryotic cells, by deamidation of a glutamine residue. This modification promotes new activities in cells, such as gene transcription, cell proliferation and survival. Since the Rho GTPases play a pivotal role also in several processes in vivo, the potentiality of CNF1 to act as a new pharmacological tool has been explored in experimental animals and in diverse pathological contexts. In this review, we give an update overview on the potential in vivo applications of CNF1. PMID- 22069585 TI - Detection of fumonisin b1 and ochratoxin a in grain products using microsphere based fluid array immunoassays. AB - Grain products are a staple of diets worldwide and therefore, the ability to accurately and efficiently detect foodborne contaminants such as mycotoxins is of importance to everyone. Here we describe an indirect competitive fluid array fluoroimmunoassay to quantify the mycotoxins, fumonisin B1 and ochratoxin A. Both toxins were immobilized to the surface of microspheres using a variety of intermediate molecules and binding of biotinylated "tracer" antibody tracers determined through flow cytometry using streptavidin-phycoerythrin conjugates and the Luminex100 flow cytometer. Competitive assays were developed where the binding of biotinylated monoclonal antibodies to fumonisin B and ochratoxin A was competitively inhibited by different concentrations of those toxins in solution. Concentrations of fumonisin giving 50% inhibition were 300 pg/mL in buffer, 100 ng/g in spiked oats, and 1 MUg/g in spiked cornmeal; analogous concentrations for ochratoxin A were 30 ng/mL in buffer, 30 ng/g in spiked oats, and 10 ng/g in spiked corn. The future challenge will be to expand the number of mycotoxins tested both individually and in multiplexed format using this platform. PMID- 22069586 TI - Cholera toxin: an intracellular journey into the cytosol by way of the endoplasmic reticulum. AB - Cholera toxin (CT), an AB(5)-subunit toxin, enters host cells by binding the ganglioside GM1 at the plasma membrane (PM) and travels retrograde through the trans-Golgi Network into the endoplasmic reticulum (ER). In the ER, a portion of CT, the enzymatic A1-chain, is unfolded by protein disulfide isomerase and retro translocated to the cytosol by hijacking components of the ER associated degradation pathway for misfolded proteins. After crossing the ER membrane, the A1-chain refolds in the cytosol and escapes rapid degradation by the proteasome to induce disease by ADP-ribosylating the large G-protein Gs and activating adenylyl cyclase. Here, we review the mechanisms of toxin trafficking by GM1 and retro-translocation of the A1-chain to the cytosol. PMID- 22069587 TI - A pilot study of nuclear instability in archived renal and upper urinary tract tumours with putative ochratoxin aetiology. AB - DNA ploidy measurement has been applied uniquely to wax-embedded tissue of primary renal cell and metastatic tumours of a key experimental researcher on porcine ochratoxicosis, a control, and four transitional cell carcinomas from cases of Balkan endemic nephropathy. Primary renal tumour was diploid, and hyperdiploid metastasis was within the lower ploidy range for typical renal cell carcinoma. Three Balkan primary tumours showed extensive aneuploidy indicating marked nuclear instability, similar to model rat renal carcinoma caused by ochratoxin A. In contrast, much less nuclear instability in the putative occupational ochratoxicosis case fitted poorly with the ochratoxin A model. PMID- 22069588 TI - Porphyromonas gingivalis gingipains trigger a proinflammatory response in human monocyte-derived macrophages through the p38alpha mitogen-activated protein kinase signal transduction pathway. AB - Porphyromonas gingivalis, the major etiologic agent of chronic periodontitis, produces a broad spectrum of virulence factors, including Arg- and Lys-gingipain cysteine proteinases. In this study, we investigated the capacity of P. gingivalis gingipains to trigger a proinflammatory response in human monocyte derived macrophages. Both Arg- and Lys-gingipain preparations induced the secretion of TNF-alpha and IL-8 by macrophages. Stimulation of macrophages with Arg-gingipain A/B preparation at the highest concentration was associated with lower amounts of cytokines detected, a phenomenon likely related to proteolytic degradation. The inflammatory response induced by gingipains was not dependent of their catalytic activity since heat-inactivated preparations were still effective. Stimulating macrophages with gingipain preparations was associated with increased levels of phosphorylated p38alpha MAPK suggesting its involvement in cell activation. In conclusion, our study brought clear evidence that P. gingivalis Arg- and Lys-gingipains may contribute to the host inflammatory response, a critical factor in periodontitis-associated tissue destruction. PMID- 22069589 TI - Environmental factors and interactions with mycobiota of grain and grapes: effects on growth, deoxynivalenol and ochratoxin production by Fusarium culmorum and Aspergillus carbonarius. AB - Mycotoxigenic fungi colonizing food matrices are inevitably competing with a wide range of other resident fungi. The outcomes of these interactions are influenced by the prevailing environmental conditions and the competing species. We have evaluated the competitiveness of F. culmorum and A. carbonarius in the grain and grape food chain for their in vitro and in situ dominance in the presence of other fungi, and the effect that such interactions have on colony interactions, growth and deoxynivalenol (DON) and ochratoxin A (OTA) production. The Index of Dominance shows that changes in water activity (a(w)) and temperature affect the competitiveness of F. culmorum and A. carbonarius against up to nine different fungi. Growth of both mycotoxigenic species was sometimes inhibited by the presence of other competing fungi. For example, A. niger uniseriate and biseriate species decreased growth of A. carbonarius, while Aureobasidium pullulans and Cladosporium species stimulated growth. Similar changes were observed when F. graminearum was interacting with other grain fungi such as Alternaria alternata, Cladopsorium herbarum and Epicoccum nigrum. The impact on DON and OTA production was very different. For F. culmorum, the presence of other species often inhibited DON production over a range of environmental conditions. For A. carbonarius, on a grape-based medium, the presence of certain species resulted in a significant stimulation of OTA production. However, this was influenced by both temperature and a(w) level. This suggests that the final mycotoxin concentrations observed in food matrices may be due to complex interactions between species and the environmental history of the samples analyzed. PMID- 22069590 TI - Role of the osmotic stress regulatory pathway in morphogenesis and secondary metabolism in filamentous fungi. AB - Environmental stimuli trigger an adaptative cellular response to optimize the probability of survival and proliferation. In eukaryotic organisms from mammals to fungi osmotic stress, mainly through the action of the high osmolarity glycerol (HOG) pathway, leads to a response necessary for adapting and surviving hyperosmotic environments. In this review we show that the osmoadaptative response is conserved but not identical in different fungi. The osmoadaptative response system is also intimately linked to morphogenesis in filamentous fungi, including mycotoxin producers. Previous studies indicate that the response to osmotic stress is also coupled to the biosynthesis of natural products, including mycotoxins. PMID- 22069591 TI - Development of an electrochemical immunosensor for fumonisins detection in foods. AB - An electrochemical affinity sensor for the determination of fumonisins mycotoxins (Fms) using monoclonal antibody modified screen-printed gold electrode with carbon counter and silver-silver chloride pseudo-reference electrode is reported in this work. A direct competitive enzyme-linked immunosorbent assay (ELISA) was initially developed, exhibiting a detection limit of 100 ug.L(-1 )for fumonisins. This was then transferred to the surface of a bare gold screen-printed electrode (SPGE) and detection was performed by chronoamperometry, monitoring the reaction of 3,3',5,5'-Tetramethylbenzidine dihydrochloride (TMB) and hydrogen peroxide (H(2)O(2)) catalysed by HRP at -100 mV potential vs. onboard Ag-AgCl pseudo reference electrode. The immunosensor exhibited detection limit of 5 ug.L(-1) fumonisins with a dynamic range from 1 ug.L(-1)-1000 ug.L(-1). The sensor also performed well in extracted corn samples. PMID- 22069592 TI - The black Aspergillus species of maize and peanuts and their potential for mycotoxin production. AB - The black spored fungi of the subgenera Circumdata, the section Nigri (=Aspergillus niger group) is reviewed relative to their production of mycotoxins and their effects on plants as pathogens. Molecular methods have revealed more than 18 cryptic species, of which several have been characterized as potential mycotoxin producers. Others are defined as benign relative to their ability to produce mycotoxins. However, these characterizations are based on in vitro culture and toxins production. Several can produce the ochratoxins that are toxic to livestock, poultry, and humans. The black aspergilli produce rots of grapes, maize, and numerous other fruits and grain and they are generally viewed as post harvest pathogens. Data are review to suggest that black aspergilli, as so many others, are symptomless endophytes. These fungi and their mycotoxins contaminate several major grains, foodstuffs, and products made from them such as wine, and coffee. Evidence is presented that the black aspergilli are producers of other classes of mycotoxins such as the fumonisins, which are known carcinogenic and known prior investigations as being produced by the Fusarium species. Three species are identified in U.S. maize and peanuts as symptomless endophytes, which suggests the potential for concern as pathogens and as food safety hazards. PMID- 22069593 TI - Inhibition of hemorragic snake venom components: old and new approaches. AB - Snake venoms are complex toxin mixtures. Viperidae and Crotalidae venoms, which are hemotoxic, are responsible for most of the envenomations around the world. Administration of antivenins aimed at the neutralization of toxins in humans is prone to potential risks. Neutralization of snake venom toxins has been achieved through different approaches: plant extracts have been utilized in etnomedicine. Direct electric current from low voltage showed neutralizing properties against venom phospholipase A2 and metalloproteases. This mini-review summarizes new achievements in venom key component inhibition. A deeper knowledge of alternative ways to inhibit venom toxins may provide supplemental treatments to serum therapy. PMID- 22069595 TI - Effects of aflatoxin B(1) and fumonisin B(1) on blood biochemical parameters in broilers. AB - The individual and combined effects of dietary aflatoxin B(1 )(AFB(1)) and fumonisin B(1) (FB(1)) on liver pathology, serum levels of aspartate amino transferase (AST) and plasma total protein (TP) of broilers were evaluated from 8 to 41 days of age. Dietary treatments included a 3 * 3 factorial arrangement with three levels of AFB(1 )(0, 50 and 200 MUg AFB(1)/kg), and three levels of FB(1 )(0, 50 and 200 mg FB(1)/kg). At 33 days post feeding, with the exception of birds fed 50 mg FB(1 )only, concentrations of AST were higher (p < 0.05) in all other treatment groups when compared with controls. Plasma TP was lower (p < 0.05) at six days post feeding in groups fed 200 MUg AFB(1)/kg alone or in combination with FB(1). At day 33 days post feeding, with the exception of birds fed the highest combination of AFB(1 )and FB(1 )which had higher plasma TP than control birds(, )plasma TP of birds fed other dietary treatments were similar to controls. Broilers receiving the highest levels of AFB(1) and FB(1) had bile duct proliferation and trabecular disorder in liver samples. AFB(1) singly or in combination with FB at the levels studied, caused liver damage and an increase in serum levels of AST. PMID- 22069594 TI - Toxins-useful biochemical tools for leukocyte research. AB - Leukocytes are a heterogeneous group of cells that display differences in anatomic localization, cell surface phenotype, and function. The different subtypes include e.g., granulocytes, monocytes, dendritic cells, T cells, B cells and NK cells. These different cell types represent the cellular component of innate and adaptive immunity. Using certain toxins such as pertussis toxin, cholera toxin or clostridium difficile toxin, the regulatory functions of Galpha(i), Galphas and small GTPases of the Rho family in leukocytes have been reported. A summary of these reports is discussed in this review. PMID- 22069596 TI - Ochratoxin a: general overview and actual molecular status. AB - Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show that this molecule can have several toxicological effects such as nephrotoxic, hepatotoxic, neurotoxic, teratogenic and immunotoxic. A role in the etiology of Balkan endemic nephropathy and its association to urinary tract tumors has been also proved. In this review, we will explore the general aspect of OTA: physico chemical properties, toxicological profile, OTA producing fungi, contaminated food, regulation, legislation and analytical methods. Due to lack of sufficient information related to the molecular background, this paper will discuss in detail the recent advances in molecular biology of OTA biosynthesis, based on information and on new data about identification and characterization of ochratoxin biosynthetic genes in both Penicillium and Aspergillus species. This review will also cover the development of the molecular methods for the detection and quantification of OTA producing fungi in various foodstuffs. PMID- 22069597 TI - Venom proteins of the parasitoid wasp Nasonia vitripennis: recent discovery of an untapped pharmacopee. AB - Adult females of Nasonia vitripennis inject a venomous mixture into its host flies prior to oviposition. Recently, the entire genome of this ectoparasitoid wasp was sequenced, enabling the identification of 79 venom proteins. The next challenge will be to unravel their specific functions, but based on homolog studies, some predictions already can be made. Parasitization has an enormous impact on hosts physiology of which five major effects are discussed in this review: the impact on immune responses, induction of developmental arrest, increases in lipid levels, apoptosis and nutrient releases. The value of deciphering this venom is also discussed. PMID- 22069599 TI - Oncological outcomes in rats given nephrocarcinogenic exposure to dietary ochratoxin a, followed by the tumour promoter sodium barbital for life: a pilot study. AB - The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young rats, of a hybrid in which mononuclear leukaemia was rare, were given feed contaminated (5 ppm) with OTA for 36 weeks to initiate renal tumourigenesis. Some individuals were thereafter given sodium barbitate (500 ppm in drinking water) for life. Pathological outcomes were studied at or near the end of natural life. Renal tumours in males given barbitate became evident after latency of one year, but only slightly before those without barbitate. In contrast, female mammary tumourigenesis was advanced by at least 6 months synchronously in all rats given the OTA-barbitate regimen compared to tumourigenesis in controls. Diagnosis of malignant mammary angiosarcoma in a female given the OTA-barbitate regimen is a new finding in the rat. The long latency of OTA-induced renal tumourigenesis was not notably susceptible to accelerated promotion by barbitate, contrasting with an apparently marked effect of barbitate on development of mammary tumours. PMID- 22069598 TI - Phytochemicals in cancer prevention and therapy: truth or dare? AB - A voluminous literature suggests that an increase in consumption of fruit and vegetables is a relatively easy and practical strategy to reduce significantly the incidence of cancer. The beneficial effect is mostly associated with the presence of phytochemicals in the diet. This review focuses on a group of them, namely isothiocyanate, curcumin, genistein, epigallocatechin gallate, lycopene and resveratrol, largely studied as chemopreventive agents and with potential clinical applications. Cellular and animal studies suggest that these molecules induce apoptosis and arrest cell growth by pleiotropic mechanisms. The anticancer efficacy of these compounds may result from their use in monotherapy or in association with chemotherapeutic drugs. This latter approach may represent a new pharmacological strategy against several types of cancers. However, despite the promising results from experimental studies, only a limited number of clinical trials are ongoing to assess the therapeutic efficacy of these molecules. Nevertheless, the preliminary results are promising and raise solid foundations for future investigations. PMID- 22069600 TI - Real and perceived risks for mycotoxin contamination in foods and feeds: challenges for food safety control. AB - Mycotoxins are toxic compounds, produced by the secondary metabolism of toxigenic moulds in the Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys genera occurring in food and feed commodities both pre- and post harvest. Adverse human health effects from the consumption of mycotoxins have occurred for many centuries. When ingested, mycotoxins may cause a mycotoxicosis which can result in an acute or chronic disease episode. Chronic conditions have a much greater impact, numerically, on human health in general, and induce diverse and powerful toxic effects in test systems: some are carcinogenic, mutagenic, teratogenic, estrogenic, hemorrhagic, immunotoxic, nephrotoxic, hepatotoxic, dermotoxic and neurotoxic. Although mycotoxin contamination of agricultural products still occurs in the developed world, the application of modern agricultural practices and the presence of a legislatively regulated food processing and marketing system have greatly reduced mycotoxin exposure in these populations. However, in developing countries, where climatic and crop storage conditions are frequently conducive to fungal growth and mycotoxin production, much of the population relies on subsistence farming or on unregulated local markets. Therefore both producers and governmental control authorities are directing their efforts toward the implementation of a correct and reliable evaluation of the real status of contamination of a lot of food commodity and, consequently, of the impact of mycotoxins on human and animal health. PMID- 22069601 TI - Biological profile of erucin: a new promising anticancer agent from cruciferous vegetables. AB - Consumption of cruciferous vegetables has been associated with a reduced risk in the development of various types of cancer. This has been attributed to the bioactive hydrolysis products that are derived from these vegetables, namely isothiocyanates. Erucin is one such product derived from rocket salads, which is structurally related to sulforaphane, a well-studied broccoli-derived isothiocyanate. In this review, we present current knowledge on mechanisms of action of erucin in chemoprevention obtained from cell and animal models and relate it to other isothiocyanates. These mechanisms include modulation of phase I, II and III detoxification, regulation of cell growth by induction of apoptosis and cell cycle arrest, induction of ROS-mechanisms and regulation androgen receptor pathways. PMID- 22069603 TI - The effects of cholera toxin on cellular energy metabolism. AB - Multianalyte microphysiometry, a real-time instrument for simultaneous measurement of metabolic analytes in a microfluidic environment, was used to explore the effects of cholera toxin (CTx). Upon exposure of CTx to PC-12 cells, anaerobic respiration was triggered, measured as increases in acid and lactate production and a decrease in the oxygen uptake. We believe the responses observed are due to a CTx-induced activation of adenylate cyclase, increasing cAMP production and resulting in a switch to anaerobic respiration. Inhibitors (H-89, brefeldin A) and stimulators (forskolin) of cAMP were employed to modulate the CTx-induced cAMP responses. The results of this study show the utility of multianalyte microphysiometry to quantitatively determine the dynamic metabolic effects of toxins and affected pathways. PMID- 22069602 TI - Biosynthesis and toxicological effects of patulin. AB - Patulin is a toxic chemical contaminant produced by several species of mold, especially within Aspergillus, Penicillium and Byssochlamys. It is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes. Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. The biosynthetic pathway consists of approximately 10 steps, as suggested by biochemical studies. Recently, a cluster of 15 genes involved in patulin biosynthesis was reported, containing characterized enzymes, a regulation factor and transporter genes. This review includes information on the current understanding of the mechanisms of patulin toxinogenesis and summarizes its toxicological effects. PMID- 22069604 TI - Studies on carcinogenic and toxic effects of ochratoxin A in chicks. AB - Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-beta-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver. PMID- 22069605 TI - Clostridial neurotoxins: mechanism of SNARE cleavage and outlook on potential substrate specificity reengineering. AB - The clostridial neurotoxin family consists of tetanus neurotoxin and seven distinct botulinum neurotoxins which cause the diseases tetanus and botulism. The extreme potency of these toxins primarily relies not only on their ability to specifically enter motoneurons but also on the activity their catalytic domains display inside presynaptic motoneuronal terminals. Subsequent to neurotoxin binding and endocytosis the catalytic domains become translocated across endosomal membranes and proteolyze unique peptide bonds of one of three soluble N ethylmaleimide-sensitive fusion protein attachment receptors (SNAREs), vesicle associated membrane protein/synaptobrevin, synaptosome associated protein of 25 kDa, or syntaxin. As these substrate proteins are core components of the vesicular membrane fusion apparatus, cleavage of any of the substrate molecules results in the blockade of neurotransmitter release. This review summarizes the present knowledge about the molecular basis of the specific substrate recognition and cleavage mechanism and assesses the feasibility of reengineering catalytic domains to hydrolyze non-substrate members of the three SNARE families in order to expand the therapeutic application of botulinum neurotoxins. PMID- 22069607 TI - Antigenotoxic studies of different substances to reduce the DNA damage induced by aflatoxin B(1) and ochratoxin A. AB - Mycotoxins are produced mainly by the mycelial structure of filamentous fungi, or more specifically, molds. These secondary metabolites are synthesized during the end of the exponential growth phase and appear to have no biochemical significance in fungal growth and development. The contamination of foods and feeds with mycotoxins is a significant problem for the adverse effects on humans, animals, and crops that result in illnesses and economic losses. The toxic effect of the ingestion of mycotoxins in humans and animals depends on a number of factors including intake levels, duration of exposure, toxin species, mechanisms of action, metabolism, and defense mechanisms. In general, the consumption of contaminated food and feed with mycotoxin induces to neurotoxic, immunosuppressive, teratogenic, mutagenic, and carcinogenic effect in humans and/or animals. The most significant mycotoxins in terms of public health and agronomic perspective include the aflatoxins, ochratoxin A (OTA), trichothecenes, fumonisins, patulin, and the ergot alkaloids. Due to the detrimental effects of these mycotoxins, several strategies have been developed in order to reduce the risk of exposure. These include the degradation, destruction, inactivation or removal of mycotoxins through chemical, physical and biological methods. However, the results obtained with these methods have not been optimal, because they may change the organoleptic characteristics and nutritional values of food. Another alternative strategy to prevent or reduce the toxic effects of mycotoxins is by applying antimutagenic agents. These substances act according to several extra- or intracellular mechanisms, their main goal being to avoid the interaction of mycotoxins with DNA; as a consequence of their action, these agents would inhibit mutagenesis and carcinogenesis. This article reviews the main strategies used to control AFB(1) and ochratoxin A and contains an analysis of some antigenotoxic substances that reduce the DNA damage caused by these mycotoxins. PMID- 22069608 TI - Ochratoxin A and aflatoxins in liquorice products. AB - The occurrence of ochratoxin A (OTA) and aflatoxins (AFs) in liquorice products made in Italy was surveyed. Twenty-eight samples of dried liquorice extract and fifty-four of liquorice confectionery (liquorice content between 2 and 10%) were collected from retail outlets located in northern Italy. After extraction and purification through an immunoaffinity column, OTA and AFs were analysed using both HPLC-FLD and HPLC-MS/MS. OTA occurred in all samples of dried liquorice extract and in 61% of samples of liquorice confectionery, showing very high values for the former (mean 89.6 ug kg(-1), maximum value 990.1 ug kg(-1)), and relatively low levels for the latter (mean 0.96 ug kg (-1), maximum value 8.3 ug kg (-1)). The contribution of dried liquorice extract to OTA intake appears to be non-negligible for children, who are potentially high consumers. AF contamination resulted very low: AFB (1) was detected only in 15.8% of samples (maximum value 7.7 ug kg (-1), mean 0.38 and 0.41 ug kg (-1) for dried liquorice extract and liquorice confectionery, respectively); the other AFs were not detected. To our knowledge, it is the first time that AFB (1) has been detected in liquorice extract samples. PMID- 22069609 TI - Ochratoxins-food contaminants: impact on human health. AB - Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus easily detected in serum. Dietary intake studies have confirmed link between endemic nephrotoxicity in humans to their daily household intake of OTA. OTA has been reported to contribute to endemic nephrotoxicity and carcinogenicity in humans and animals. OTA produces renal tumours, DNA adducts and chromosomal aberrations in kidneys. OTA may be embryotoxic, teratogenic, and immunotoxic only at doses higher than those causing nephrotoxicity. The incidence of endemic nephrotoxicity has been mostly reported in northeast Europe since the early fifties. Recent studies however have warned that OTA and other toxins, such as aristolochic acid, show very similar renal pathology. There is thus the need for thorough co-occurrence studies on toxin incidence. PMID- 22069610 TI - Ochratoxin A and beta2-microglobulin in BEN patients and controls. AB - Ochratoxin A (OTA) is a mycotoxin naturally occurring in different foods. OTA is arguably a risk factor for Balkan endemic nephropathy (BEN). The aims of this study are to (1) test the OTA-BEN association in BEN-groups and controls and (2) determine whether urine beta2-microglobulin, a marker of impaired ability of the kidneys to re-absorb, is related to OTA. BEN patients had significantly higher OTA serum levels. Within the offspring, OTA was significantly related to higher beta2-microglobulin excretion. OTA (2005/2006) was related to a higher incidence of BEN after 2008, providing further evidence that OTA is a risk factor for BEN. PMID- 22069606 TI - Bacterial toxins and the nervous system: neurotoxins and multipotential toxins interacting with neuronal cells. AB - Toxins are potent molecules used by various bacteria to interact with a host organism. Some of them specifically act on neuronal cells (clostridial neurotoxins) leading to characteristics neurological affections. But many other toxins are multifunctional and recognize a wider range of cell types including neuronal cells. Various enterotoxins interact with the enteric nervous system, for example by stimulating afferent neurons or inducing neurotransmitter release from enterochromaffin cells which result either in vomiting, in amplification of the diarrhea, or in intestinal inflammation process. Other toxins can pass the blood brain barrier and directly act on specific neurons. PMID- 22069611 TI - Fibrolase: trials and tribulations. AB - Fibrolase is the fibrinolytic enzyme isolated from Agkistrodon contortrix contortrix (southern copperhead snake) venom. The enzyme was purified by a three step HPLC procedure and was shown to be homogeneous by standard criteria including reverse phase HPLC, molecular sieve chromatography and SDS-PAGE. The purified enzyme is a zinc metalloproteinase containing one mole of zinc. It is composed of 203 amino acids with a blocked amino-terminus due to cyclization of the terminal Gln residue. Fibrolase shares a significant degree of homology with enzymes of the reprolysin sub-family of metalloproteinases including an active site homology of close to 100%; it is rapidly inhibited by chelating agents such as EDTA, and by alpha2-macroglobulin (alpha2MU). The enzyme is a direct-acting thrombolytic agent and does not rely on plasminogen for clot dissolution. Fibrolase rapidly cleaves the A(alpha)-chain of fibrinogen and the B(beta)-chain at a slower rate; it has no activity on the gamma-chain. The enzyme exhibits the same specificity with fibrin, cleaving the alpha-chain more rapidly than the beta chain. Fibrolase was shown to have very effective thrombolytic activity in a reoccluding carotid arterial thrombosis model in the canine. A recombinant version of the enzyme was made in yeast by Amgen, Inc. (Thousand Oaks, CA, USA) and called alfimeprase. Alfimeprase is identical to fibrolase except for a two amino acid truncation at the amino-terminus and the insertion of a new amino terminal amino acid in the truncated protein; these changes lead to a more stable enzyme for prolonged storage. Alfimeprase was taken into clinical trials by Nuvelo, Inc. (San Carlos, CA), which licensed the enzyme from Amgen. Alfimeprase was successful in Phase I and II clinical trials for peripheral arterial occlusion (PAO) and central venous access device (CVAD) occlusion. However, in Phase III trials alfimeprase did not meet the expected end points in either PAO or CVAD occlusion and in a Phaase II stroke trial, and Nuvelo dropped further development in 2008. PMID- 22069612 TI - Ochratoxin A in ruminants-A review on its degradation by gut microbes and effects on animals. AB - Ruminants are much less sensitive to ochratoxin A (OTA) than non-ruminants. The ruminal microbes, with protozoa being a central group, degrade the mycotoxin extensively, with disappearance half lives of 0.6-3.8 h. However, in some studies OTA was detected systemically when using sensitive analytical methods, probably due to some rumen bypass at proportions of estimated 2-6.5% of dosage (maximum 10%). High concentrate proportions and high feeding levels are dietary factors promoting the likeliness of systemic occurrence due to factors like shifts in microbial population and higher contamination potential. Among risk scenarios for ruminants, chronic intoxication represents the most relevant. PMID- 22069613 TI - Occurrence of black aspergilli and ochratoxin A on grapes in Italy. AB - Ochratoxin A (OTA) in wine is linked to contamination by several Aspergillus species. In 2003-2007, grape samples collected in Italy were surveyed for the presence of OTA and OTA-producing fungi. A. niger aggregate was the prevalent species. A. carbonarius, which is considered the main source of OTA in grapes, was mostly found in Southern Italy. The year and the environment had an important influence on the development of the black Aspergillus populations. Testing with ELISA showed OTA to be present in about 30% of the samples. Samples from Southern Italy showed the highest occurrence (45%) and also the highest OTA concentration, sometimes higher than 2 MUg/L. The values decreased progressively the further North the samples were taken. PMID- 22069614 TI - The double-edged sword of autoimmunity: lessons from multiple sclerosis. AB - The relationship between immune responses to self-antigens and autoimmune disease is unclear. In contrast to its animal model experimental autoimmune encephalomyelitis (EAE), which is driven by T cell responses to myelin antigens, the target antigen of the intrathecal immune response in multiple sclerosis (MS) has not been identified. Although the immune response in MS contributes significantly to tissue destruction, the action of immunocompetent cells within the central nervous system (CNS) may also hold therapeutic potential. Thus, treatment of MS patients with glatiramer acetate triggers a protective immune response. Here we review the immunopathogenesis of MS and some recent findings on the mechanism of glatiramer acetate (GA). PMID- 22069615 TI - Marine toxins: chemistry, toxicity, occurrence and detection, with special reference to the Dutch situation. AB - Various species of algae can produce marine toxins under certain circumstances. These toxins can then accumulate in shellfish such as mussels, oysters and scallops. When these contaminated shellfish species are consumed severe intoxication can occur. The different types of syndromes that can occur after consumption of contaminated shellfish, the corresponding toxins and relevant legislation are discussed in this review. Amnesic Shellfish Poisoning (ASP), Paralytic Shellfish Poisoning (PSP), Diarrheic Shellfish Poisoning (DSP) and Azaspiracid Shellfish Poisoning (AZP) occur worldwide, Neurologic Shellfish Poisoning (NSP) is mainly limited to the USA and New Zealand while the toxins causing DSP and AZP occur most frequently in Europe. The latter two toxin groups are fat-soluble and can therefore also be classified as lipophilic marine toxins. A detailed overview of the official analytical methods used in the EU (mouse or rat bioassay) and the recently developed alternative methods for the lipophilic marine toxins is given. These alternative methods are based on functional assays, biochemical assays and chemical methods. From the literature it is clear that chemical methods offer the best potential to replace the animal tests that are still legislated worldwide. Finally, an overview is given of the situation of marine toxins in The Netherlands. The rat bioassay has been used for monitoring DSP and AZP toxins in The Netherlands since the 1970s. Nowadays, a combination of a chemical method and the rat bioassay is often used. In The Netherlands toxic events are mainly caused by DSP toxins, which have been found in Dutch shellfish for the first time in 1961, and have reoccurred at irregular intervals and in varying concentrations. From this review it is clear that considerable effort is being undertaken by various research groups to phase out the animal tests that are still used for the official routine monitoring programs. PMID- 22069616 TI - AIP56: a novel bacterial apoptogenic toxin. AB - Photobacterium damselae subsp. piscicida (Phdp) is a Gram-negative pathogen agent of an important fish septicemia. The key virulence factor of Phdp is the plasmid encoded exotoxin AIP56, which is secreted by exponentially growing pathogenic strains. AIP56 has 520 amino acids including an N-terminal cleavable signal peptide of 23 amino acid residues, two cysteine residues and a zinc-binding region signature HEXXH that is typical of most zinc metallopeptidases. AIP56 induces in vitro and in vivo selective apoptosis of fish macrophages and neutrophils through a caspase-3 dependent mechanism that also involves caspase-8 and -9. In vivo, the AIP56-induced phagocyte apoptosis progresses to secondary necrosis with release of cytotoxic phagocyte molecules including neutrophil elastase. Fish injected with recombinant AIP56 die with a pathology similar to that seen in the natural infection. PMID- 22069617 TI - Discovery and characterization of proteins associated with aflatoxin-resistance: evaluating their potential as breeding markers. AB - Host resistance has become a viable approach to eliminating aflatoxin contamination of maize since the discovery of several maize lines with natural resistance. However, to derive commercial benefit from this resistance and develop lines that can aid growers, markers need to be identified to facilitate the transfer of resistance into commercially useful genetic backgrounds without transfer of unwanted traits. To accomplish this, research efforts have focused on the identification of kernel resistance-associated proteins (RAPs) including the employment of comparative proteomics to investigate closely-related maize lines that vary in aflatoxin accumulation. RAPs have been identified and several further characterized through physiological and biochemical investigations to determine their causal role in resistance and, therefore, their suitability as breeding markers. Three RAPs, a 14 kDa trypsin inhibitor, pathogenesis-related protein 10 and glyoxalase I are being investigated using RNAi gene silencing and plant transformation. Several resistant lines have been subjected to QTL mapping to identify loci associated with the aflatoxin-resistance phenotype. Results of proteome and characterization studies are discussed. PMID- 22069618 TI - Proteases as insecticidal agents. AB - Proteases from a variety of sources (viruses, bacteria, fungi, plants, and insects) have toxicity towards insects. Some of these insecticidal proteases evolved as venom components, herbivore resistance factors, or microbial pathogenicity factors, while other proteases play roles in insect development or digestion, but exert an insecticidal effect when over-expressed from genetically engineered plants or microbial pathogens. Many of these proteases are cysteine proteases, although insect-toxic metalloproteases and serine proteases have also been examined. The sites of protease toxic activity range from the insect midgut to the hemocoel (body cavity) to the cuticle. This review discusses these insecticidal proteases along with their evaluation and use as potential pesticides. PMID- 22069619 TI - The role of lymphostatin/EHEC factor for adherence-1 in the pathogenesis of gram negative infection. AB - Lymphostatin/EHEC factor for adherence-1 is a novel large toxin represented in various Gram negative bacteria, highly associated with the development of infectious diarrhea and hemolytic uremic syndrome. In vitro and in vivo experiments identified lymphostatin/EFA-1 as a toxin with a central role in the pathogenesis of Gram negative bacteria, responsible for bacterial adhesion, intestinal colonization, immunosuppression, and disruption of gut epithelial barrier function. PMID- 22069620 TI - Autoproteolytic activation of bacterial toxins. AB - Protease domains within toxins typically act as the primary effector domain within target cells. By contrast, the primary function of the cysteine protease domain (CPD) in Multifunctional Autoprocessing RTX-like (MARTX) and Clostridium sp. glucosylating toxin families is to proteolytically cleave the toxin and release its cognate effector domains. The CPD becomes activated upon binding to the eukaryotic-specific small molecule, inositol hexakisphosphate (InsP(6)), which is found abundantly in the eukaryotic cytosol. This property allows the CPD to spatially and temporally regulate toxin activation, making it a prime candidate for developing anti-toxin therapeutics. In this review, we summarize recent findings related to defining the regulation of toxin function by the CPD and the development of inhibitors to prevent CPD-mediated activation of bacterial toxins. PMID- 22069621 TI - The zinc-dependent protease activity of the botulinum neurotoxins. AB - The botulinum neurotoxins (BoNT, serotypes A-G) are some of the most toxic proteins known and are the causative agents of botulism. Following exposure, the neurotoxin binds and enters peripheral cholinergic nerve endings and specifically and selectively cleaves one or more SNARE proteins to produce flaccid paralysis. This review centers on the kinetics of the Zn-dependent proteolytic activities of these neurotoxins, and briefly describes inhibitors, activators and factors underlying persistence of toxin action. Some of the structural, enzymatic and inhibitor data that are discussed here are available at the botulinum neurotoxin resource, BotDB (http://botdb.abcc.ncifcrf.gov). PMID- 22069622 TI - Toxin-specific antibodies for the treatment of Clostridium difficile: current status and future perspectives. AB - Therapeutic agents targeting bacterial virulence factors are gaining interest as non-antibiotic alternatives for the treatment of infectious diseases. Clostridium difficile is a Gram-positive pathogen that produces two primary virulence factors, enterotoxins A and B (TcdA and TcdB), which are responsible for Clostridium difficile-associated disease (CDAD) and are targets for CDAD therapy. Antibodies specific for TcdA and TcdB have been shown to effectively treat CDAD and prevent disease relapse in animal models and in humans. This review summarizes the various toxin-specific antibody formats and strategies under development, and discusses future directions for CDAD immunotherapy, including the use of engineered antibody fragments with robust biophysical properties for systemic and oral delivery. PMID- 22069623 TI - A review on toxic and harmful algae in Greek coastal waters (E. Mediterranean Sea). AB - The Greek coastal waters are subjected to harmful algal bloom (HAB) phenomena due to the occurrence of species characterized as toxic (TX), potentially toxic (PT), and non-toxic, high biomass (HB) producers causing harm at multiple levels. The total number of (TX), (PT) and (HB) algae reported in this work are 61, but only 16 species have been associated with the occurrence of important HABs causing damage in the marine biota and the water quality. These phenomena are sporadic in time, space and recurrence of the causative species, and are related to the anthropogenically-induced eutrophication conditions prevailing in the investigated areas. PMID- 22069624 TI - Consequences and utility of the zinc-dependent metalloprotease activity of anthrax lethal toxin. AB - Anthrax is caused by the gram-positive bacterium Bacillus anthracis. The pathogenesis of this disease is dependent on the presence of two binary toxins, edema toxin (EdTx) and lethal toxin (LeTx). LeTx, the major virulence factor contributing to anthrax, contains the effector moiety lethal factor (LF), a zinc dependent metalloprotease specific for targeting mitogen-activated protein kinase kinases. This review will focus on the protease-specific activity and function of LF, and will include a discussion on the implications and consequences of this activity, both in terms of anthrax disease, and how this activity can be exploited to gain insight into other pathologic conditions. PMID- 22069625 TI - Occurrence of ochratoxin A in Southern Spanish generous wines under the denomination of Origin "Jerez-Xeres-Sherry and 'manzanilla' Sanlucar de Barrameda". AB - The mycotoxin ochratoxin A (OTA) has toxic effects in animals; the most relevant of them is nephrotoxicity. OTA has also been classified as a possible carcinogen for humans (group 2B) by the International Agency for Research on Cancer (IARC). Therefore, exposure to OTA through contaminated food can represent health impairment to humans. The maximum permitted level for this mycotoxin in wine is 2.0 MUg/L. The presence of OTA in Spanish wines produced using the traditional methods under the Denomination of Origin "Jerez-Xeres-Sherry andmanzanilla Sanlucar de Barrameda" was evaluated by a High performance Liquid Chromatography method with fluorescence detection and immunoaffinity column purification. A recovery of 95.4% and a limit of detection and quantification of 0.009 MUg/L and 0.02 MUg/L respectively, were achieved. In manzanilla, fino, amontillado and oloroso wine, the mean OTA values were 0.042, 0.044, 0.144, and 0.319 MUg/L, respectively. These levels are not different from other data given in the reference literature on white wines, although fino and manzanilla wines have very low OTA levels. PMID- 22069626 TI - Ochratoxins in feed, a risk for animal and human health: control strategies. AB - Ochratoxin A (OTA) has been shown to be a potent nephrotoxic, hepatotoxic, and teratogenic compound. In farm animals, the intake of feed contaminated with OTA affects animal health and productivity, and may result in the presence of OTA in the animal products. Strategies for the control of OTA in food products require early identification and elimination of contaminated commodities from the food chain. However, current analytical protocols may fail to identify contaminated products, especially in animal feed. The present paper discusses the impact of OTA on human and animal health, with special emphasis on the potential risks of OTA residue in animal products, and control strategies applied in the feed industry. PMID- 22069628 TI - Pathological outcomes in kidney and brain in male Fischer rats given dietary ochratoxin A, commencing at one year of age. AB - Malignant renal carcinoma, manifest in morbid ageing rats, is the striking component of an otherwise silent response after about nine months of exposure to ochratoxin A in the first year of life (daily intake ~100-250 ug/kg body weight). Reasons for the long latency are unclear, as is whether there would be a similar carcinogenic response if toxin exposure started at one year of age. Therefore, 24 male Fischer rats were given 100 ug ochratoxin A as a daily dietary contaminant for 35 weeks from age 50 weeks. Plasma ochratoxin A concentration reached a maximum value of ~8 ug/mL within one month of starting the toxin regimen. No renal carcinomas occurred. Four renal adenomas, two of which were only microscopic, were found among the six rats surviving for 110 weeks. The findings raise new questions about a difference between young adults and mature adults in sensitivity of male rats to the ochratoxin A-induced DNA damage necessary for renal carcinogenesis. A pilot histological study of perfuse-fixed brains of the toxin-treated rats showed no gross abnormalities, correlating with the consistent absence of behavioral or neurological disorders from chronic ochratoxin A exposure regimens in the range 100-250 ug/kg/day during the second half of life. Reasoned questioning concerning ochratoxin A as a neurotoxic mycotoxin is made. PMID- 22069627 TI - Biodegradation of ochratoxin a for food and feed decontamination. AB - Ochratoxin A (OTA) is one of the most important mycotoxins that is found in food and feed products. It has proven toxic properties, being primarily known for its nephrotoxicity and carcinogenicity to certain animal species. OTA is produced by several species of Aspergillus and Penicillium that can be found in a wide variety of agricultural products, which makes the presence of OTA in these products common. Many countries have statutory limits for OTA, and concentrations need to be reduced to as low as technologically possible in food and feed. The most important measures to be taken to control OTA are preventive in order to avoid fungal growth and OTA production. However, these measures are difficult to implement in all cases with the consequence of OTA remaining in agricultural commodities. Remediation processes are often used to eliminate, reduce or avoid the toxic effects of OTA. Biological methods have been considered increasingly as an alternative to physical and chemical treatments. However, examples of practical applications are infrequent. This review will focus on the (i) known microorganisms and enzymes that are able to biodegrade OTA; (ii) mode of action of biodegradation and (iii) current applications. A critical discussion about the technical applicability of these strategies is presented. PMID- 22069629 TI - Ochratoxin A producing species in the genus Penicillium. AB - Ochratoxin A (OTA) producing fungi are members of the genera Aspergillus and Penicillium. Nowadays, there are about 20 species accepted as OTA producers, which are distributed in three phylogenetically related but distinct groups of aspergilli of the subgenus Circumdati and only in two species of the subgenus Penicillium. At the moment, P. verrucosum and P. nordicum are the only OTA producing species accepted in the genus Penicillium. However, during the last century, OTA producers in this genus were classified as P. viridicatum for many years. At present, only some OTA producing species are known to be a potential source of OTA contamination of cereals and certain common foods and beverages such as bread, beer, coffee, dried fruits, grape juice and wine among others. Penicillium verrucosum is the major producer of OTA in cereals such as wheat and barley in temperate and cold climates. Penicillium verrucosum and P. nordicum can be recovered from some dry-cured meat products and some cheeses. PMID- 22069630 TI - Ochratoxin A in Moroccan foods: occurrence and legislation. AB - Ochratoxin A (OTA) is secondary metabolite naturally produced in food and feed by toxigenic fungi, especially some Aspergillus species and Penicillium verucosum. OTA is one of the most studied mycotoxins and is of great interest due to its toxic effects on human and animals. OTA is produced in different food and feed matrices and contaminates a large range of base foods including cereals and derivatives, spices, dried fruits, wine and coffee, etc. Morocco, a North African country, has a climate characterized by high humidity and temperature, which probably favors the growth of molds. This contribution gives an overview of principal investigations about the presence of OTA in foods available in Morocco. Due to its toxicity, OTA presence is increasingly regulated worldwide, especially in countries of the European Union. However, up until now, no regulation limits were in force in Morocco, probably due to the ignorance of the health and economic problems resulting from OTA contamination. Finally, recommendations and future research directions are given required to assess the situation completely. PMID- 22069632 TI - Comparative study of various immune parameters in three bivalve species during a natural bloom of Dinophysis acuminata in Santa Catarina Island, Brazil. AB - This study aimed to verify if Dinophysis acuminata natural blooms affected the immune system of three bivalves: the oyster, Crassostrea gigas, the mussel, Perna perna, and the clam, Anomalocardia brasiliana. Animals were obtained from a renowned mariculture farm in the southern bay of Santa Catarina Island during, and 30 days after (controls), an algal bloom. Various immunological parameters were assessed in the hemolymph of the animals: total and differential hemocyte counts, percentage of apoptotic hemocytes, protein concentration, hemagglutinating titer and phenoloxidase activity. The results showed that the mussel was the most affected species, with several altered immune parameters, whereas the immunological profile of clams and oysters was partially and completely unaffected, respectively. PMID- 22069631 TI - Exfoliative toxins of Staphylococcus aureus. AB - Staphylococcus aureus is an important pathogen of humans and livestock. It causes a diverse array of diseases, ranging from relatively harmless localized skin infections to life-threatening systemic conditions. Among multiple virulence factors, staphylococci secrete several exotoxins directly associated with particular disease symptoms. These include toxic shock syndrome toxin 1 (TSST-1), enterotoxins, and exfoliative toxins (ETs). The latter are particularly interesting as the sole agents responsible for staphylococcal scalded skin syndrome (SSSS), a disease predominantly affecting infants and characterized by the loss of superficial skin layers, dehydration, and secondary infections. The molecular basis of the clinical symptoms of SSSS is well understood. ETs are serine proteases with high substrate specificity, which selectively recognize and hydrolyze desmosomal proteins in the skin. The fascinating road leading to the discovery of ETs as the agents responsible for SSSS and the characterization of the molecular mechanism of their action, including recent advances in the field, are reviewed in this article. PMID- 22069633 TI - Serine protease autotransporters of enterobacteriaceae (SPATEs): biogenesis and function. AB - Serine Protease Autotransporters of Enterobacteriaceae (SPATEs) constitute a large family of proteases secreted by Escherichia coli and Shigella. SPATEs exhibit two distinct proteolytic activities. First, a C-terminal catalytic site triggers an intra-molecular cleavage that releases the N-terminal portion of these proteins in the extracellular medium. Second, the secreted N-terminal domains of SPATEs are themselves proteases; each contains a canonical serine protease catalytic site. Some of these secreted proteases are toxins, eliciting various effects on mammalian cells. Here, we discuss the biogenesis of SPATEs and their function as toxins. PMID- 22069634 TI - Overcoming multidrug resistance in human cancer cells by natural compounds. AB - Multidrug resistance is a phenomenon whereby tumors become resistant to structurally unrelated anticancer drugs. P-glycoprotein belongs to the large ATP binding cassette (ABC) transporter superfamily of membrane transport proteins. P glycoprotein mediates resistance to various classes of anticancer drugs including vinblastine, daunorubicin, and paclitaxel, by actively extruding the drugs from the cells. The quest for inhibitors of anticancer drug efflux transporters has uncovered natural compounds, including (-)-epigallocatechin gallate, curcumin, capsaicin, and guggulsterone, as promising candidates. In this review, studies on the effects of natural compounds on P-glycoprotein and anticancer drug efflux transporters are summarized. PMID- 22069635 TI - Ochratoxin a in Portugal: a review to assess human exposure. AB - In Portugal, the climate, dietary habits, and food contamination levels present the characteristics for higher population susceptibility to ochratoxin A (OTA), one of the known mycotoxins with the greatest public health and agro-economic importance. In this review, following a brief historical insight on OTA research, a summary of the available data on OTA occurrence in food (cereals, bread, wine, meat) and biological fluids (blood, urine) is made. With this data, an estimation of intake is made to ascertain and update the risk exposure estimation of the Portuguese population, in comparison to previous studies and other populations. PMID- 22069637 TI - Alpha-tocopherol counteracts the cytotoxicity induced by ochratoxin a in primary porcine fibroblasts. AB - The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of alpha-tocopherol in counteracting its toxicity. Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre incubation for 3 h with 1 nM alpha-tocopherol significantly (P < 0.01) reduced OTA cytotoxicity, lactate dehydrogenase release and DNA damage in both fibroblast cultures. These findings indicate that alpha-tocopherol supplementation may counteract short-term OTA toxicity, supporting its defensive role in the cell membrane. PMID- 22069636 TI - Toxins and secretion systems of Photorhabdus luminescens. AB - Photorhabdus luminescens is a nematode-symbiotic, gram negative, bioluminescent bacterium, belonging to the family of Enterobacteriaceae. Recent studies show the importance of this bacterium as an alternative source of insecticides, as well as an emerging human pathogen. Various toxins have been identified and characterized in this bacterium. These toxins are classified into four major groups: the toxin complexes (Tcs), the Photorhabdus insect related (Pir) proteins, the "makes caterpillars floppy" (Mcf) toxins and the Photorhabdus virulence cassettes (PVC); the mechanisms however of toxin secretion are not fully elucidated. Using bioinformatics analysis and comparison against the components of known secretion systems, multiple copies of components of all known secretion systems, except the ones composing a type IV secretion system, were identified throughout the entire genome of the bacterium. This indicates that Photorhabdus luminescens has all the necessary means for the secretion of virulence factors, thus it is capable of establishing a microbial infection. PMID- 22069638 TI - Differential cell sensitivity between OTA and LPS upon releasing TNF-alpha. AB - The release of tumor necrosis factor alpha (TNF-alpha) by ochratoxin A (OTA) was studied in various macrophage and non-macrophage cell lines and compared with E. coli lipopolysaccharide (LPS) as a standard TNF-alpha release agent. Cells were exposed either to 0, 2.5 or 12.5 umol/L OTA, or to 0.1 ug/mL LPS, for up to 24 h. OTA at 2.5 umol/L and LPS at 0.1 ug/mL were not toxic to the tested cells as indicated by viability markers. TNF-alpha was detected in the incubated cell medium of rat Kupffer cells, peritoneal rat macrophages, and the mouse monocyte macrophage cell line J774A.1: TNF-alpha concentrations were 1,000 pg/mL, 1,560 pg/mL, and 650 pg/mL, respectively, for 2.5 umol/L OTA exposure and 3,000 pg/mL, 2,600 pg/mL, and 2,115 pg/mL, respectively, for LPS exposure. Rat liver sinusoidal endothelial cells, rat hepatocytes, human HepG2 cells, and mouse L929 cells lacked any cytokine response to OTA, but showed a significant release of TNF-alpha after LPS exposure, with the exception of HepG2 cells. In non responsive cell lines, OTA lacked both any activation of NF-kappaB or the translocation of activated NF-kappaB to the cell nucleus, i.e., in mouse L929 cells. In J774A.1 cells, OTA mediated TNF-alpha release via the pRaf/MEK 1/2-NF kappaB and p38-NF-kappaB pathways, whereas LPS used pRaf/MEK 1/2-NF-kappaB, but not p38-NF-kappaB pathways. In contrast, in L929 cells, LPS used other pathways to activate NF-kappaB. Our data indicate that only macrophages and macrophage derived cells respond to OTA and are considered as sources for TNF-alpha release upon OTA exposure. PMID- 22069639 TI - Deoxynivalenol-induced proinflammatory gene expression: mechanisms and pathological sequelae. AB - The trichothecene mycotoxin deoxynivalenol (DON) is commonly encountered in human cereal foods throughout the world as a result of infestation of grains in the field and in storage by the fungus Fusarium. Significant questions remain regarding the risks posed to humans from acute and chronic DON ingestion, and how to manage these risks without imperiling access to nutritionally important food commodities. Modulation of the innate immune system appears particularly critical to DON's toxic effects. Specifically, DON induces activation of mitogen-activated protein kinases (MAPKs) in macrophages and monocytes, which mediate robust induction of proinflammatory gene expression-effects that can be recapitulated in intact animals. The initiating mechanisms for DON-induced ribotoxic stress response appear to involve the (1) activation of constitutive protein kinases on the damaged ribosome and (2) autophagy of the chaperone GRP78 with consequent activation of the ER stress response. Pathological sequelae resulting from chronic low dose exposure include anorexia, impaired weight gain, growth hormone dysregulation and aberrant IgA production whereas acute high dose exposure evokes gastroenteritis, emesis and a shock-like syndrome. Taken together, the capacity of DON to evoke ribotoxic stress in mononuclear phagocytes contributes significantly to its acute and chronic toxic effects in vivo. It is anticipated that these investigations will enable the identification of robust biomarkers of effect that will be applicable to epidemiological studies of the human health effects of this common mycotoxin. PMID- 22069640 TI - Shiga toxin is transported into the nucleoli of intestinal epithelial cells via a carrier-dependent process. AB - Shiga toxin (Stx) produced by the invasive Shigella dysenteriae serotype 1 (S. dysenteriae1) causes gastrointestinal and kidney complications. It has been assumed that Stx is released intracellularly after enterocyte invasion by S. dysenteriae1. However, there is little information about Stx distribution inside S. dysenteriae1-infected enterocytes. Here, we use intestinal epithelial T84 cells to characterize the trafficking of Stx delivered into the cytosol, in ways that mimic aspects of S. dysenteriae1 infection. We find that cytoplasmic Stx is transported into nucleoli. Stx nucleolar movement is carrier- and energy dependent. Stx binding to the nucleoli of normal human enterocytes in vitro supports possible roles for nucleolar trafficking in toxin-induced intestinal pathology. PMID- 22069641 TI - On the interaction of Clostridium perfringens enterotoxin with claudins. AB - Clostridium perfringens causes one of the most common foodborne illnesses, which is largely mediated by the Clostridium perfringens enterotoxin (CPE). The toxin consists of two functional domains. The N-terminal region mediates the cytotoxic effect through pore formation in the plasma membrane of the mammalian host cell. The C-terminal region (cCPE) binds to the second extracellular loop of a subset of claudins. Claudin-3 and claudin-4 have been shown to be receptors for CPE with very high affinity. The toxin binds with weak affinity to claudin-1 and -2 but contribution of these weak binding claudins to CPE-mediated disease is questionable. cCPE is not cytotoxic, however, it is a potent modulator of tight junctions. This review describes recent progress in the molecular characterization of the cCPE-claudin interaction using mutagenesis, in vitro binding assays and permeation studies. The results promote the development of recombinant cCPE-proteins and CPE-based peptidomimetics to modulate tight junctions for improved drug delivery or to treat tumors overexpressing claudins. PMID- 22069643 TI - Molecular mechanism of ochratoxin a transport in the kidney. AB - The mycotoxin, ochratoxin A (OTA), is thought to be responsible for Balkan endemic nephropathy. OTA accumulates in several tissues, especially in the kidneys and liver. The excretion of OTA into urine is thought to be mainly by tubular secretion, presumably via the organic anion transport system. Recently, several families of multispecific organic anion transporters have been identified: organic anion transporters (OATs), organic anion-transporting polypeptides (OATPs), oligopeptide transporters (PEPTs), and ATP-binding cassette (ABC) transporters, such as MRP2 and BCRP. These renal transporters mediate the transmembrane transport of OTA and play a pivotal role in the development of OTA induced nephrotoxicity. PMID- 22069644 TI - Effect of antioxidant mixtures on growth and ochratoxin a production of Aspergillus section Nigri species under different water activity conditions on peanut meal extract agar. AB - The effect of mixtures of antioxidants butylated hydroxyanisol (BHA) and propyl paraben (PP) on lag phase, growth rate and ochratoxin A (OTA) production by four Aspergillus section Nigri strains was evaluated on peanut meal extract agar (PMEA) under different water activities (a(w)). The antioxidant mixtures used were: BHA + PP (mM), M1 (0.5 + 0.5), M2 (1.0 + 0.5), M3 (2.5 + 0.5), M4 (0.5 + 1.0), M5 (1.0 + 1.0), M6 (2.5 + 1.0), M7 (5.0 + 2.5) and M8 (10 + 2.5). The mixture M8 completely suppressed mycelial growth for all strains. A significant stimulation in OTA production was observed with mixtures M1 to M5 mainly at the highest a(w); whereas M6, M7 and M8 completely inhibited OTA production in all strains assayed; except M6 in A. carbonarius strain (RCP G). These results could enable a future intervention strategy to minimize OTA contamination. PMID- 22069642 TI - The glucocorticoid receptor: a revisited target for toxins. AB - The hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the HPA axis or GR blockade enhances mortality rates. Replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. Glucocorticoid resistance/insensitivity is a common problem in the treatment of many diseases. Much research has focused on the molecular mechanism behind this resistance, but an area that has been neglected is the role of infectious agents and toxins. We have recently shown that the anthrax lethal toxin is able to repress glucocorticoid receptor function. Data suggesting that the glucocorticoid receptor may be a target for a variety of toxins is reviewed here. These studies have important implications for glucocorticoid therapy. PMID- 22069645 TI - "Suspects" in etiology of endemic nephropathy: aristolochic acid versus mycotoxins. AB - Despite many hypotheses that have been challenged, the etiology of endemic nephropathy (EN) is still unknown. At present, the implications of aristolochic acid (AA) and mycotoxins (ochratoxin A-OTA and citrinin-CIT) are under debate. AA theory is based on renal pathohistological similarities between Chinese herbs nephropathy (CHN) and EN, findings of AA-DNA adducts in EN and in patients with urinary tract tumors (UTT), as well as the domination of A:T(r)T:A transversions in the p53 mutational spectrum of UTT patients, which corresponds with findings of such mutations in AA-treated rats. However, exposure pathways of EN residents to AA are unclear. Experimental studies attempting to deduce whether nephrotoxins OTA and CIT appear at higher frequencies or levels (or both) in the food and blood or urine of EN residents support the mycotoxin theory. Also, some molecular studies revealed the presence of OTA-DNA adducts in the renal tissue of EN and UTT patients. In this review, data supporting or arguing against AA and mycotoxin theory are presented and discussed. PMID- 22069646 TI - Heat-labile enterotoxin: beyond G(m1) binding. AB - Enterotoxigenic Escherichia coli (ETEC) is a significant source of morbidity and mortality worldwide. One major virulence factor released by ETEC is the heat labile enterotoxin LT, which is structurally and functionally similar to cholera toxin. LT consists of five B subunits carrying a single catalytically active A subunit. LTB binds the monosialoganglioside G(M1), the toxin's host receptor, but interactions with A-type blood sugars and E. coli lipopolysaccharide have also been identified within the past decade. Here, we review the regulation, assembly, and binding properties of the LT B-subunit pentamer and discuss the possible roles of its numerous molecular interactions. PMID- 22069647 TI - Synthetic alpha-conotoxin mutants as probes for studying nicotinic acetylcholine receptors and in the development of novel drug leads. AB - alpha-Conotoxins are peptide neurotoxins isolated from venomous marine cone snails that are potent and selective antagonists for different subtypes of nicotinic acetylcholine receptors (nAChRs). As such, they are valuable probes for dissecting the role that nAChRs play in nervous system function. In recent years, extensive insight into the binding mechanisms of alpha-conotoxins with nAChRs at the molecular level has aided in the design of synthetic analogs with improved pharmacological properties. This review examines the structure-activity relationship studies involving alpha-conotoxins as research tools for studying nAChRs in the central and peripheral nervous systems and their use towards the development of novel therapeutics. PMID- 22069649 TI - Molecularly imprinted polymers for ochratoxin a extraction and analysis. AB - Molecularly imprinted polymers (MIPs) are considered as polymeric materials that mimic the functionality of antibodies. MIPs have been utilized for a wide variety of applications in chromatography, solid phase extraction, immunoassays, and sensor recognition. In this article, recent advances of MIPs for the extraction and analysis of ochratoxins are discussed. Selection of functional monomers to bind ochratoxin A (OTA) with high affinities, optimization of extraction procedures, and limitations of MIPs are compared from different reports. The most relevant examples in the literature are described to clearly show how useful these materials are. Strategies on MIP preparation and schemes of analytical methods are also reviewed in order to suggest the next step that would make better use of MIPs in the field of ochratoxin research. The review ends by outlining the remaining issues and impediments. PMID- 22069650 TI - Arsenic in cancer treatment: challenges for application of realgar nanoparticles (a minireview). AB - While intensive efforts have been made for the treatment of cancer, this disease is still the second leading cause of death in many countries. Metastatic breast cancer, late-stage colon cancer, malignant melanoma, multiple myeloma, and other forms of cancer are still essentially incurable in most cases. Recent advances in genomic technologies have permitted the simultaneous evaluation of DNA sequence based alterations together with copy number gains and losses. The requirement for a multi-targeting approach is the common theme that emerges from these studies. Therefore, the combination of new targeted biological and cytotoxic agents is currently under investigation in multimodal treatment regimens. Similarly, a combinational principle is applied in traditional Chinese medicine, as formulas consist of several types of medicinal herbs or minerals, in which one represents the principal component, and the others serve as adjuvant ones that assist the effects, or facilitate the delivery, of the principal component. In Western medicine, approximately 60 different arsenic preparations have been developed and used in pharmacological history. In traditional Chinese medicines, different forms of mineral arsenicals (orpiment-As(2)S(3), realgar-As(4)S(4), and arsenolite-arsenic trioxide, As(2)O(3)) are used, and realgar alone is included in 22 oral remedies that are recognized by the Chinese Pharmacopeia Committee (2005). It is known that a significant portion of some forms of mineral arsenicals is poorly absorbed into the body, and would be unavailable to cause systemic damage. This review primary focuses on the application of arsenic sulfide (realgar) for treatment of various forms of cancer in vitro and in vivo. PMID- 22069648 TI - Shiga toxins: intracellular trafficking to the ER leading to activation of host cell stress responses. AB - Despite efforts to improve hygenic conditions and regulate food and drinking water safety, the enteric pathogens, Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae serotype 1 remain major public health concerns due to widespread outbreaks and the severity of extra-intestinal diseases they cause, including acute renal failure and central nervous system complications. Shiga toxins are the key virulence factors expressed by these pathogens mediating extra-intestinal disease. Delivery of the toxins to the endoplasmic reticulum (ER) results in host cell protein synthesis inhibition, activation of the ribotoxic stress response, the ER stress response, and in some cases, the induction of apoptosis. Intrinsic and/or extrinsic apoptosis inducing pathways are involved in executing cell death following intoxication. In this review we provide an overview of the current understanding Shiga toxin intracellular trafficking, host cellular responses to the toxin and ER stress-induced apoptosis with an emphasis on recent findings. PMID- 22069651 TI - Development and characterization of a monoclonal antibody against Ochratoxin B and its application in ELISA. AB - A monoclonal antibody specific to ochratoxin B (OTB) was employed for the development of an indirect competitive OTB-ELISA. The optimized OTB-ELISA resulted in a limit of detection (LOD) for OTB of 3 ug/L (8 nM), a limit of quantification (LOQ) of 3.7 ug/L (10 nM), and a 50% inhibitory concentration (IC(50)) of 150 nM. Due to very low cross-reactivity to OTA (2.7%) and structurally related molecules (0%), this OTB-ELISA was found to be suitable to detect OTB with excellent precision in different matrices, i.e., beer, coffee and wine. Therefore, this OTB-ELISA will allow screening of OTB in food and feed products. PMID- 22069652 TI - Specificity of interaction between clostridium perfringens enterotoxin and claudin-family tight junction proteins. AB - Clostridium perfringens enterotoxin (CPE), a major cause of food poisoning, forms physical pores in the plasma membrane of intestinal epithelial cells. The ability of CPE to recognize the epithelium is due to the C-terminal binding domain, which binds to a specific motif on the second extracellular loop of tight junction proteins known as claudins. The interaction between claudins and CPE plays a key role in mediating CPE toxicity by facilitating pore formation and by promoting tight junction disassembly. Recently, the ability of CPE to distinguish between specific claudins has been used to develop tools for studying roles for claudins in epithelial barrier function. Moreover, the high affinity of CPE to selected claudins makes CPE a useful platform for targeted drug delivery to tumors expressing these claudins. PMID- 22069655 TI - Plant Natural compounds with antibacterial activity towards common pathogens of pond-cultured channel catfish (Ictalurus punctatus). AB - The bacteria Edwardsiella ictaluri and Flavobacterium columnare cause enteric septicemia and columnaris disease, respectively, in channel catfish (Ictalurus punctatus). Natural therapeutants may provide an alternative to current management approaches used by producers. In this study, a rapid bioassay identified plant compounds as potential therapeutants. Chelerythrine chloride and ellagic acid were the most toxic toward E. ictaluri, with 24-h IC50 of 7.3 mg/L and 15.1 mg/L, respectively, and MIC of 2.1 mg/L and 6.5 mg/L, respectively. Chelerythrine chloride, ellagic acid, beta-glycyrrhetinic acid, sorgoleone, and wogonin were the most toxic towards two genomovars of F. columnare, and wogonin had the strongest antibacterial activity (MIC = 0.3 mg/L). PMID- 22069653 TI - AB toxins: a paradigm switch from deadly to desirable. AB - To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity. PMID- 22069654 TI - Neurological disease rises from ocean to bring model for human epilepsy to life. AB - Domoic acid of macroalgal origin was used for traditional and medicinal purposes in Japan and largely forgotten until its rediscovery in diatoms that poisoned 107 people after consumption of contaminated mussels. The more severely poisoned victims had seizures and/or amnesia and four died; however, one survivor unexpectedly developed temporal lobe epilepsy (TLE) a year after the event. Nearly a decade later, several thousand sea lions have stranded on California beaches with neurological symptoms. Analysis of the animals stranded over an eight year period indicated five clusters of acute neurological poisoning; however, nearly a quarter have stranded individually outside these events with clinical signs of a chronic neurological syndrome similar to TLE. These poisonings are not limited to sea lions, which serve as readily observed sentinels for other marine animals that strand during domoic acid poisoning events, including several species of dolphin and whales. Acute domoic acid poisoning is five-times more prominent in adult female sea lions as a result of the proximity of their year-round breeding grounds to major domoic acid bloom events. The chronic neurological syndrome, on the other hand, is more prevalent in young animals, with many potentially poisoned in utero. The sea lion rookeries of the Channel Islands are at the crossroads of domoic acid producing harmful algal blooms and a huge industrial discharge site for dichlorodiphenyltrichloroethane (DDTs). Studies in experimental animals suggest that chronic poisoning observed in immature sea lions may result from a spatial and temporal coincidence of DDTs and domoic acid during early life stages. Emergence of an epilepsy syndrome from the ocean brings a human epilepsy model to life and provides unexpected insights into interaction with legacy contaminants and expression of disease at different life stages. PMID- 22069656 TI - Production, secretion and biological activity of Bacillus cereus enterotoxins. AB - Bacillus cereus behaves as an opportunistic pathogen frequently causing gastrointestinal diseases, and it is increasingly recognized to be responsible for severe local or systemic infections. Pathogenicity of B. cereus mainly relies on the secretion of a wide array of toxins and enzymes and also on the ability to undergo swarming differentiation in response to surface-sensing. In this report, the pathogenicity exerted by B. cereus toxins is described with particular attention to the regulatory mechanisms of production and secretion of HBL, Nhe and CytK enterotoxins. PMID- 22069657 TI - Uncoupling of T cell receptor zeta chain function during the induction of anergy by the superantigen, staphylococcal enterotoxin A. AB - Staphylococcus aureus enterotoxins have immunomodulatory properties. In this study, we show that Staphylococcal enterotoxin A (SEA) induces a strong proliferative response in a murine T cell clone independent of MHC class II bearing cells. SEA stimulation also induces a state of hypo-responsiveness (anergy). We characterized the components of the T cell receptor (TCR) during induction of anergy by SEA. Most interestingly, TCR zeta chain phosphorylation was absent under SEA anergizing conditions, which suggests an uncoupling of zeta chain function. We characterize here a model system for studying anergy in the absence of confounding costimulatory signals. PMID- 22069658 TI - Chemical, physical and biological approaches to prevent ochratoxin induced toxicoses in humans and animals. AB - Ochratoxins are polyketide derived fungal secondary metabolites with nephrotoxic, immunosuppressive, teratogenic, and carcinogenic properties. Ochratoxin-producing fungi may contaminate agricultural products in the field (preharvest spoilage), during storage (postharvest spoilage), or during processing. Ochratoxin contamination of foods and feeds poses a serious health hazard to animals and humans. Several strategies have been investigated for lowering the ochratoxin content in agricultural products. These strategies can be classified into three main categories: prevention of ochratoxin contamination, decontamination or detoxification of foods contaminated with ochratoxins, and inhibition of the absorption of consumed ochratoxins in the gastrointestinal tract. This paper gives an overview of the strategies that are promising with regard to lowering the ochratoxin burden of animals and humans. PMID- 22069659 TI - Food poisoning and Staphylococcus aureus enterotoxins. AB - Staphylococcus aureus produces a wide variety of toxins including staphylococcal enterotoxins (SEs; SEA to SEE, SEG to SEI, SER to SET) with demonstrated emetic activity, and staphylococcal-like (SEl) proteins, which are not emetic in a primate model (SElL and SElQ) or have yet to be tested (SElJ, SElK, SElM to SElP, SElU, SElU2 and SElV). SEs and SEls have been traditionally subdivided into classical (SEA to SEE) and new (SEG to SElU2) types. All possess superantigenic activity and are encoded by accessory genetic elements, including plasmids, prophages, pathogenicity islands, vSa genomic islands, or by genes located next to the staphylococcal cassette chromosome (SCC) implicated in methicillin resistance. SEs are a major cause of food poisoning, which typically occurs after ingestion of different foods, particularly processed meat and dairy products, contaminated with S. aureus by improper handling and subsequent storage at elevated temperatures. Symptoms are of rapid onset and include nausea and violent vomiting, with or without diarrhea. The illness is usually self-limiting and only occasionally it is severe enough to warrant hospitalization. SEA is the most common cause of staphylococcal food poisoning worldwide, but the involvement of other classical SEs has been also demonstrated. Of the new SE/SEls, only SEH have clearly been associated with food poisoning. However, genes encoding novel SEs as well as SEls with untested emetic activity are widely represented in S. aureus, and their role in pathogenesis may be underestimated. PMID- 22069660 TI - Cholera-like enterotoxins and Regulatory T cells. AB - Cholera toxin (CT) and the heat-labile enterotoxin of E. coli (LT), as well as their non toxic mutants, are potent mucosal adjuvants of immunization eliciting mucosal and systemic responses against unrelated co-administered antigens in experimental models and in humans (non toxic mutants). These enterotoxins are composed of two subunits, the A subunit, responsible for an ADP-ribosyl transferase activity and the B subunit, responsible for cell binding. Paradoxically, whereas the whole toxins have adjuvant properties, the B subunits of CT (CTB) and of LT (LTB) have been shown to induce antigen specific tolerance when administered mucosally with antigens in experimental models as well as, recently, in humans, making them an attractive strategy to prevent or treat autoimmune or allergic disorders. Immunomodulation is a complex process involving many cell types notably antigen presenting cells and regulatory T cells (Tregs). In this review, we focus on Treg cells and cholera-like enterotoxins and their non toxic derivates, with regard to subtype, in vivo/in vitro effects and possible role in the modulation of immune responses to coadministered antigens. PMID- 22069661 TI - Effects of ochratoxin a on livestock production. AB - Ochratoxin A (OTA) contamination often causes large economic losses on livestock production. The intake of feed contaminated by OTA also represents a potential risk for animal health and a food safety issue due to the transfer of the toxin through the food chain to humans. The aim of this paper is to review the available literature on: (1) the frequency and degree of occurrence of OTA in different feedstuffs; (2) the toxicological effects of OTA intake on the performance of the main livestock (i.e., poultry, swine, cattle, goats and sheep); and (3) the transfer of OTA, or its metabolites, from animal feed into animal products such as milk, meat and eggs. PMID- 22069663 TI - Emergence of anthrax edema toxin as a master manipulator of macrophage and B cell functions. AB - Anthrax edema toxin (ET), a powerful adenylyl cyclase, is an important virulence factor of Bacillus anthracis. Until recently, only a modest amount of research was performed to understand the role this toxin plays in the organism's immune evasion strategy. A new wave of studies have begun to elucidate the effects this toxin has on a variety of host cells. While efforts have been made to illuminate the effect ET has on cells of the adaptive immune system, such as T cells, the greatest focus has been on cells of the innate immune system, particularly the macrophage. Here we discuss the immunoevasive activities that ET exerts on macrophages, as well as new research on the effects of this toxin on B cells. PMID- 22069662 TI - The enterotoxicity of Clostridium difficile toxins. AB - The major virulence factors of Clostridium difficile infection (CDI) are two large exotoxins A (TcdA) and B (TcdB). However, our understanding of the specific roles of these toxins in CDI is still evolving. It is now accepted that both toxins are enterotoxic and proinflammatory in the human intestine. Both purified TcdA and TcdB are capable of inducing the pathophysiology of CDI, although most studies have focused on TcdA. C. difficile toxins exert a wide array of biological activities by acting directly on intestinal epithelial cells. Alternatively, the toxins may target immune cells and neurons once the intestinal epithelial barrier is disrupted. The toxins may also act indirectly by stimulating cells to produce chemokines, proinflammatory cytokines, neuropeptides and other neuroimmune signals. This review considers the mechanisms of TcdA- and TcdB-induced enterotoxicity, and recent developments in this field. PMID- 22069664 TI - The systemic and pulmonary immune response to staphylococcal enterotoxins. AB - In response to environmental cues the human pathogen Staphylococcus aureus synthesizes and releases proteinaceous enterotoxins. These enterotoxins are natural etiologic entities of severe food poisoning, toxic shock syndrome, and acute diseases. Staphylococcal enterotoxins are currently listed as Category B Bioterrorism Agents by the Center for Disease Control and Prevention. They are associated with respiratory illnesses, and may contribute to exacerbation of pulmonary disease. This likely stems from the ability of Staphylococcal enterotoxins to elicit powerful episodes of T cell stimulation resulting in release of pro-inflammatory cytokines. Here, we discuss the role of the immune system and potential mechanisms of disease initiation and progression. PMID- 22069665 TI - NetB, a pore-forming toxin from necrotic enteritis strains of Clostridium perfringens. AB - The Clostridium perfringens necrotic enteritis B-like toxin (NetB) is a recently discovered member of the beta-barrel pore-forming toxin family and is produced by a subset of avian C. perfringens type A strains. NetB is cytotoxic for avian cells and is associated with avian necrotic enteritis. This review examines the current state of knowledge of NetB: its role in pathogenesis, its distribution and expression in C. perfringens and its vaccine potential. PMID- 22069666 TI - Ochratoxin A in roasted coffee from French supermarkets and transfer in coffee beverages: comparison of analysis methods. AB - The OTA content of 30 roasted coffees purchased in French supermarkets was evaluated by two validated different methods: one using immunoaffinity column (IAC) clean-up after alkaline extraction; the second using toluene extraction under acidic conditions. OTA recoveries (0.5 to 5 ug/kg) ranged from 16-49% with the alkaline extraction method and 55-60% with the acidic method. OTA recoveries from prepared beverages were similar with all methods (75-80%). All samples containing OTA ranged from trace (1 mg) in a 100 g sample. PMID- 22069714 TI - The use of convection-enhanced delivery with liposomal toxins in neurooncology. AB - Liposomes have long been effective delivery vehicles for transport of toxins to peripheral cancers. The combination of convection-enhanced delivery (CED) with liposomal toxins was originally proposed to circumvent the limited delivery of intravascular liposomes to the central nervous system (CNS) due to the blood brain-barrier (BBB). CED offers markedly improved distribution of infused therapeutics within the CNS compared to direct injection or via drug eluting polymers, both of which depend on diffusion for parenchymal distribution. This review examines the basis for improved delivery of liposomal toxins via CED within the CNS, and discusses preclinical and clinical experience with these therapeutic techniques. How CED and liposomal technologies may influence future neurooncologic treatments are also considered. PMID- 22069716 TI - A comparison of the anti-tumor effects of a chimeric versus murine anti-CD19 immunotoxins on human B cell lymphoma and Pre-B acute lymphoblastic leukemia cell lines. AB - Precursor B cell acute lymphoblastic leukemia (pre-B ALL) affects five to six thousand adults and almost three thousand children every year. Approximately 25% of the children and 60% of the adults die from their disease, highlighting the need for new therapies that complement rather than overlap chemotherapy and bone marrow transplantation. Immunotherapy is a class of therapies where toxicities and mechanisms of action do not overlap with those of chemotherapy. Because CD19 is a B cell- restricted membrane antigen that is expressed on the majority of pre B tumor cells, a CD19-based immunotherapy is being developed for ALL. In this study, the anti-tumor activities of immunotoxins (ITs) constructed by conjugating a murine monoclonal antibody (MAb), HD37, or its chimeric (c) construct to recombinant ricin toxin A chain (rRTA) were compared both in vitro using human pre-B ALL and Burkitt's lymphoma cell lines and in vivo using a disseminated human pre-B ALL tumor cell xenograft model. The murine and chimeric HD37 IT constructs were equally cytotoxic to pre-B ALL and Burkitt's lymphoma cells in vitro and their use in vivo resulted in equivalent increases in survival of SCID mice with human pre-B ALL tumors when compared with control mice. PMID- 22069718 TI - Accumulation kinetics of three scirpentriol-based toxins in oats inoculated in Vitro with isolates of Fusarium sporotrichioides and Fusarium poae. AB - Autoclaved oats were inoculated with a strain of Fusarium sporotrichioides or Fusarium poae. Moisture content of oats after inoculation was at 38%, incubation took place in standing culture at 28 degrees C. The A-type trichothecenes, 4,15 diacetoxyscirpenol (4,15-DAS), 15-monoacetoxyscirpenol (15-MAS), and scirpentriol (SCIRP) were analyzed by GC/MS. For each strain, three culture flasks were harvested at 2-3 day intervals starting immediately after inoculation. Total incubation time was 42 days (F. poae) and 56 days (F. sporotrichioides). Following peak accumulation, 4,15-DAS decreased below the detection limit for both strains, 15-MAS decreased below this limit for the isolate of F. sporotrichioides, for the isolate of F. poae it decreased to a level markedly below the peak value. SCIRP, after having peaked, decreased to some extent for the strain F. sporotrichioides, with a significant (P = 0.0029) negative linear regression of toxin content against culture age during this period. The content of 15-MAS, and in part also of 4,15-DAS, decreased along with an increase of SCIRP. This sequential accumulation pattern suggests the successive induction of esterases deacetylating 4,15-DAS and 15-MAS, as well as of enzymes involved in the metabolization of the parent alcohol, SCIRP. The results may explain, at least in part, the somewhat higher incidence in naturally contaminated compounds reported in the literature for SCIRP compared to 4,15-DAS and 15-MAS. PMID- 22069717 TI - Use of ribosome-inactivating proteins from Sambucus for the construction of immunotoxins and conjugates for cancer therapy. AB - The type 2 ribosome-inactivating proteins (RIPs) isolated from some species belonging to the Sambucus genus, have the characteristic that although being even more active than ricin inhibiting protein synthesis in cell-free extracts, they lack the high toxicity of ricin and related type 2 RIPs to intact cells and animals. This is due to the fact that after internalization, they follow a different intracellular pathway that does not allow them to reach the cytosolic ribosomes. The lack of toxicity of type 2 RIPs from Sambucus make them good candidates as toxic moieties in the construction of immunotoxins and conjugates directed against specific targets. Up to now they have been conjugated with either transferrin or anti-CD105 to target either transferrin receptor- or endoglin-overexpressing cells, respectively. PMID- 22069719 TI - Inhibition of the unfolded protein response by ricin a-chain enhances its cytotoxicity in mammalian cells. AB - Ricin is a highly toxic type II ribosome-inactivating protein that has potential as a biochemical weapon and as the toxic component of immunotoxins. The unfolded protein response (UPR) is a survival response that helps cells to recover from endoplasmic reticulum (ER) stress. Failure to recover from ER stress leads to apoptosis. In yeast, ricin-A-chain (RTA), the enzymatic component of ricin, inhibits UPR. Our goals were to determine if RTA inhibits UPR in two epithelial cell lines and if this affects RTA cytotoxicity. RTA alone did not induce UPR. However, RTA inhibited both phosphorylation of inositol-requiring enzyme 1 (IRE1) and splicing of X-box binding protein1 mRNA by the UPR-inducing agent tunicamycin (Tm). The ability of dithiothreitol (DTT) to activate eukaryotic translation initiation factor 2 alpha (eIF2alpha), a component of the PERK pathway, was also inhibited by RTA. Treatment with RTA in combination with Tm or DTT inhibited protein synthesis more than either agent did alone in one cell line, while caspase cleavage was enhanced by the treatment combination in both cell lines. These data indicate that RTA is more cytotoxic when UPR is inhibited. This ability to inhibit UPR may enhance the potential of RTA as a therapeutic immunotoxin in solid tumors. PMID- 22069721 TI - Alpha-latrotoxin rescues SNAP-25 from BoNT/A-mediated proteolysis in embryonic stem cell-derived neurons. AB - The botulinum neurotoxins (BoNTs) exhibit zinc-dependent proteolytic activity against members of the core synaptic membrane fusion complex, preventing neurotransmitter release and resulting in neuromuscular paralysis. No pharmacologic therapies have been identified that clinically relieve botulinum poisoning. The black widow spider venom alpha-latrotoxin (LTX) has the potential to attenuate the severity or duration of BoNT-induced paralysis in neurons via the induction of synaptic degeneration and remodeling. The potential for LTX to antagonize botulinum poisoning was evaluated in embryonic stem cell-derived neurons (ESNs), using a novel screening assay designed around the kinetics of BoNT/A activation. Exposure of ESNs to 400 pM LTX for 6.5 or 13 min resulted in the nearly complete restoration of uncleaved SNAP-25 within 48 h, whereas treatment with 60 mM K(+) had no effect. Time-lapse imaging demonstrated that LTX treatment caused a profound increase in Ca(2+) influx and evidence of excitotoxicity, though ESNs remained viable 48 h after LTX treatment. This is the first instance of a cell-based treatment that has shown the ability to eliminate BoNT activity. These data suggest that LTX treatment may provide the basis for a new class of therapeutic approach to BoNT intoxication and may contribute to an improved understanding of long-term mechanisms of BoNT intoxication and recovery. They further demonstrate that ESNs are a novel, responsive and biologically relevant model for LTX research and BoNT therapeutic drug discovery. PMID- 22069720 TI - Botulinum neurotoxins and botulism: a novel therapeutic approach. AB - Specific treatment is not available for human botulism. Current remedial mainstay is the passive administration of polyclonal antibody to botulinum neurotoxin (BoNT) derived from heterologous species (immunized animal or mouse hybridoma) together with supportive and symptomatic management. The antibody works extracellularly, probably by blocking the binding of receptor binding (R) domain to the neuronal receptors; thus inhibiting cellular entry of the holo-BoNT. The antibody cannot neutralize the intracellular toxin. Moreover, a conventional antibody with relatively large molecular size (150 kDa) is not accessible to the enzymatic groove and, thus, cannot directly inhibit the BoNT zinc metalloprotease activity. Recently, a 15-20 kDa single domain antibody (V(H)H) that binds specifically to light chain of BoNT serotype A was produced from a humanized camel VH/V(H)H phage display library. The V(H)H has high sequence homology (>80%) to the human VH and could block the enzymatic activity of the BoNT. Molecular docking revealed not only the interface binding between the V(H)H and the toxin but also an insertion of the V(H)H CDR3 into the toxin enzymatic pocket. It is envisaged that, by molecular linking the V(H)H to a cell penetrating peptide (CPP), the CPP-V(H)H fusion protein would be able to traverse the hydrophobic cell membrane into the cytoplasm and inhibit the intracellular BoNT. This presents a novel and safe immunotherapeutic strategy for botulism by using a cell penetrating, humanized-single domain antibody that inhibits the BoNT by means of a direct blockade of the groove of the menace enzyme. PMID- 22069722 TI - H NMR spectroscopy-based metabolomic assessment of uremic toxicity, with toxicological outcomes, in male rats following an acute, mid-life insult from ochratoxin a. AB - Overt response to a single 6.25 mg dose of ochratoxin A (OTA) by oral gavage to 15 months male rats was progressive loss of weight during the following four days. Lost weight was restored within one month and animals had a normal life span without OTA-related terminal disease. Decline in plasma OTA concentration only commenced four days after dosing, while urinary excretion of OTA and ochratoxin alpha was ongoing. During a temporary period of acute polyuria, a linear relationship between urine output and creatinine concentration persisted. Elimination of other common urinary solutes relative to creatinine was generally maintained during the polyuria phase, except that phosphate excretion increased temporarily. (1)H NMR metabolomic analysis of urine revealed a progressive cyclic shift in the group principal components data cluster from before dosing, throughout the acute insult phase, and returning almost completely to normality when tested six months later. Renal insult by OTA was detected by (1)H NMR within a day of dosing, as the most sensitive early indicator. Notable biomarkers were trimethylamine N-oxide and an aromatic urinary profile dominated by phenylacetylglycine. Tolerance of such a large acute insult by OTA, assessed by rat natural lifetime outcomes, adds a new dimension to toxicology of this xenobiotic. PMID- 22069723 TI - 4-Pyridone-3-carboxamide-1-beta-D-ribonucleoside triphosphate (4PyTP), a novel NAD metabolite accumulating in erythrocytes of uremic children: a biomarker for a toxic NAD analogue in other tissues? AB - We have identified a novel nucleotide, 4-pyridone 3/5-carboxamide ribonucleoside triphosphate (4PyTP), which accumulates in human erythrocytes during renal failure. Using plasma and erythrocyte extracts obtained from children with chronic renal failure we show that the concentration of 4PyTP is increased, as well as other soluble NAD(+) metabolites (nicotinamide, N(1)-methylnicotinamide and 4Py-riboside) and the major nicotinamide metabolite N(1)-methyl-2-pyridone-5 carboxamide (2PY), with increasing degrees of renal failure. We noted that 2PY concentration was highest in the plasma of haemodialysis patients, while 4PyTP was highest in erythrocytes of children undergoing peritoneal dialysis: its concentration correlated closely with 4Py-riboside, an authentic precursor of 4PyTP, in the plasma. In the dialysis patients, GTP concentration was elevated: similar accumulation was noted previously, as a paradoxical effect in erythrocytes during treatment with immunosuppressants such as ribavirin and mycophenolate mofetil, which deplete GTP through inhibition of IMP dehydrogenase in nucleated cells such as lymphocytes. We predict that 4Py-riboside and 4Py nucleotides bind to this enzyme and alter its activity. The enzymes that regenerate NAD(+) from nicotinamide riboside also convert the drugs tiazofurin and benzamide riboside into NAD(+) analogues that inhibit IMP dehydrogenase more effectively than the related ribosides: we therefore propose that the accumulation of 4PyTP in erythrocytes during renal failure is a marker for the accumulation of a related toxic NAD(+) analogue that inhibits IMP dehydrogenase in other cells. PMID- 22069724 TI - Expression analysis of stress-related genes in kernels of different maize (Zea mays L.) inbred lines with different resistance to aflatoxin contamination. AB - This research examined the expression patterns of 94 stress-related genes in seven maize inbred lines with differential expressions of resistance to aflatoxin contamination. The objective was to develop a set of genes/probes associated with resistance to A. flavus and/or aflatoxin contamination. Ninety four genes were selected from previous gene expression studies with abiotic stress to test the differential expression in maize lines, A638, B73, Lo964, Lo1016, Mo17, Mp313E, and Tex6, using real-time RT-PCR. Based on the relative-expression levels, the seven maize inbred lines clustered into two different groups. One group included B73, Lo1016 and Mo17, which had higher levels of aflatoxin contamination and lower levels of overall gene expression. The second group which included Tex6, Mp313E, Lo964 and A638 had lower levels of aflatoxin contamination and higher overall levels of gene expressions. A total of six "cross-talking" genes were identified between the two groups, which are highly expressed in the resistant Group 2 but down-regulated in susceptible Group 1. When further subjected to drought stress, Tex6 expressed more genes up-regulated and B73 has fewer genes up regulated. The transcript patterns and interactions measured in these experiments indicate that the resistant mechanism is an interconnected process involving many gene products and transcriptional regulators, as well as various host interactions with environmental factors, particularly, drought and high temperature. PMID- 22069725 TI - Aflatoxin toxicity reduction in feed by enhanced binding to surface-modified clay additives. AB - Animal feeding studies have demonstrated that clay additives, such as bentonites, can bind aflatoxins in ingested feed and reduce or eliminate the toxicity. Bentonite deposits are found throughout the world and mostly consist of expandable smectite minerals, such as montmorillonite. The surfaces of smectite minerals can be treated with organic compounds to create surface-modified clays that more readily bind some contaminants than the untreated clay. Montmorillonites treated with organic cations, such as hexadecyltrimethylammonium (HDTMA) and phenyltrimethylammonium (PTMA), more effectively remove organic contaminants, such as benzene and toluene, from water than untreated clay. Similarly, montmorillonite treated with PTMA (K(d) = 24,100) retained more aflatoxin B1 (AfB1) from aqueous corn flour than untreated montmorillonite (K(d) = 944). Feed additives that reduced aflatoxin toxicity in animal feeding studies adsorbed more AfB1 from aqueous corn flour than feed additives that were less effective. The organic cations HDTMA and PTMA are considered toxic and would not be suitable for clay additives used in feed or food, but other non-toxic or nutrient compounds can be used to prepare surface-modified clays. Montmorillonite (SWy) treated with choline (K(d) = 13,800) and carnitine (K(d) = 3960) adsorbed much more AfB1 from aqueous corn flour than the untreated clay (K(d) = 944). A choline-treated clay prepared from a reduced-charge, high-charge montmorillonite (K(d) = 20,100) adsorbed more AfB1 than the choline-treated high-charge montmorillonite (K(d) = 1340) or the untreated montmorillonite (K(d) = 293). Surface-modified clay additives prepared using low-charge smectites and nutrient or non-toxic organic compounds might be used to more effectively bind aflatoxins in contaminated feed or food and prevent toxicity. PMID- 22069726 TI - Aflatoxin B(1) in affecting broiler's performance, immunity, and gastrointestinal tract: a review of history and contemporary issues. AB - Aflatoxin B(1) is a common contaminant of poultry feeds in tropical and subtropical climates. Research during the last five decades has well established the negative effects of the mycotoxin on health of poultry. However, the last ten years of relevant data have accentuated the potential of low levels of aflatoxin B(1) to deteriorate broiler performance. In this regard, any attempt to establish a dose-effect relationship between aflatoxin B(1) level and broiler performance is also complicated due to differences in types of broilers and length of exposure to the mycotoxin in different studies. Contrary to the prevalent notion regarding literature saturation with respect to aflatoxicosis of chicken, many areas of aflatoxicosis still need to be explored. Literature regarding effects of the mycotoxin on the gastrointestinal tract in this regard is particular scanty and non-conclusive. In addition to these issues, the metabolism of aflatoxin B(1) and recently proposed hypotheses regarding biphasic effects of the mycotoxin in broilers are briefly discussed. PMID- 22069727 TI - The effects of anthrax lethal toxin on host barrier function. AB - The pathological actions of anthrax toxin require the activities of its edema factor (EF) and lethal factor (LF) enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA). LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs), but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT) leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects. PMID- 22069728 TI - Shiga toxin: expression, distribution, and its role in the environment. AB - In this review, we highlight recent work that has increased our understanding of the production and distribution of Shiga toxin in the environment. Specifically, we review studies that offer an expanded view of environmental reservoirs for Shiga toxin producing microbes in terrestrial and aquatic ecosystems. We then relate the abundance of Shiga toxin in the environment to work that demonstrates that the genetic mechanisms underlying the production of Shiga toxin genes are modified and embellished beyond the classical microbial gene regulatory paradigms in a manner that apparently "fine tunes" the trigger to modulate the amount of toxin produced. Last, we highlight several recent studies examining microbe/protist interactions that postulate an answer to the outstanding question of why microbes might harbor and express Shiga toxin genes in the environment. PMID- 22069729 TI - Shiga toxin interaction with human intestinal epithelium. AB - After ingestion via contaminated food or water, enterohaemorrhagic E. coli colonises the intestinal mucosa and produces Shiga toxins (Stx). No Stx-specific secretion system has been described so far, and it is assumed that Stx are released into the gut lumen after bacterial lysis. Human intestinal epithelium does not express the Stx receptor Gb3 or other Stx binding sites, and it remains unknown how Stx cross the intestinal epithelial barrier and gain access to the systemic circulation. This review summarises current knowledge about the influence of the intestinal environment on Stx production and release, Stx interaction with intestinal epithelial cells and intracellular uptake, and toxin translocation into underlying tissues. Furthermore, it highlights gaps in understanding that need to be addressed by future research. PMID- 22069730 TI - Detection of stx and stx genes in Pennsylvanian white-tailed deer. AB - Shiga toxin-producing E. coli carrying the stx(1) and/or stx(2) genes can cause multi-symptomatic illness in humans. A variety of terrestrial and aquatic environmental reservoirs of stx have been described. Culture based detection of microbes in deer species have found a low percentage of samples that have tested positive for Stx-producing microbes, suggesting that while deer may contain these microbes, their overall abundance in deer is low. In this study, quantitative PCR (qPCR) was utilized to test for the presence of stx genes in white-tailed deer fecal matter in western Pennsylvania. In this culture independent screening, nearly half of the samples tested positive for the stx(2) gene, with a bias towards samples that were concentrated with stx(2). This study, while limited in scope, suggests that deer may be a greater reservoir for stx than was previously thought. PMID- 22069731 TI - Control of aflatoxin production of Aspergillus flavus and Aspergillus parasiticus using RNA silencing technology by targeting aflD (nor-1) gene. AB - Aspergillus flavus and Aspergillus parasiticus are important pathogens of cotton, corn, peanuts and other oil-seed crops, producing toxins both in the field and during storage. We have designed three siRNA sequences (Nor-Ia, Nor-Ib, Nor-Ic) to target the mRNA sequence of the aflD gene to examine the potential for using RNA silencing technology to control aflatoxin production. Thus, the effect of siRNAs targeting of two key genes in the aflatoxin biosynthetic pathway, aflD (structural) and aflR (regulatory gene) and on aflatoxin B(1 )(AFB(1)), and aflatoxin G(1) (AFG(1)) production was examined. The study showed that Nor-Ib gave a significant decrease in aflD mRNA, aflR mRNA abundance, and AFB(1) production (98, 97 and 97% when compared to the controls) in A. flavus NRRL3357, respectively. Reduction in aflD and aflR mRNA abundance and AFB(1 )production increased with concentration of siRNA tested. There was a significant inhibition in aflD and AFB(1) production by A. flavus EGP9 and AFG(1 )production by A. parasiticus NRRL 13005. However, there was no significant decrease in AFG(1) production by A. parasiticus SSWT 2999. Changes in AFB(1) production in relation to mRNA levels of aflD showed a good correlation (R = 0.88; P = 0.00001); changes in aflR mRNA level in relation to mRNA level of aflD also showed good correlation (R = 0.82; P = 0.0001). The correlations between changes in aflR and aflD gene expression suggests a strong relationship between these structural and regulatory genes, and that aflD could be used as a target gene to develop efficient means for aflatoxin control using RNA silencing technology. PMID- 22069733 TI - Loss of vtx genes after the first subcultivation step of verocytotoxigenic Escherichia coli O157 and Non-O157 during isolation from naturally contaminated fecal samples. AB - Verocytotoxins VT1 and VT2,produced by Verocytotoxigenic Escherichia coli (VTEC), are encoded on temperate bacteriophages. Several studies reported the loss of the vtx genes after multiple subcultivation steps or long preservation. The objective of this study was to determine if the loss of the verocytotoxin genes can already occur during the first subcultivation step. Consequently, the stability of the vtx genes were tested in 40 isolates originating from 40 vtx-positive fecal samples after the first subcultivation step following the isolation procedure. The loss occurred in 12 out of 40 strains tested and was rather rare among the O157 strains compared to the non-O157 strains. This is the first study demonstrating that the loss of the verocytotoxin genes can already occur after the first subcultivation step. This may lead to an underestimation of VTEC positive samples. PMID- 22069732 TI - T cell targeting by anthrax toxins: two faces of the same coin. AB - Bacillus anthracis, similar to other bacterial pathogens, has evolved effective immune evasion strategies to prolong its survival in the host, thus ensuring the unchecked spread of the infection. This function is subserved by lethal (LT) and edema (ET) toxins, two exotoxins produced by vegetative anthrax bacilli following germination of the spores. The structure of these toxins and the mechanism of cell intoxication are topics covered by other reviews in this issue. Here we shall discuss how B. anthracis uses LT and ET to suppress the immune defenses of the host, focusing on T lymphocytes, the key players in adaptive immunity. We shall also summarize recent findings showing that, depending on its concentration, ET has the ability not only to suppress T cell activation but also to promote the polarization of CD4(+) T cells to the Th2 and Th17 subsets, highlighting the potential use of this toxin as an immunomodulator. PMID- 22069734 TI - Developing resistance to aflatoxin in maize and cottonseed. AB - At this time, no "magic bullet" for solving the aflatoxin contamination problem in maize and cottonseed has been identified, so several strategies must be utilized simultaneously to ensure a healthy crop, free of aflatoxins. The most widely explored strategy for the control of aflatoxin contamination is the development of preharvest host resistance. This is because A. flavus infects and produces aflatoxins in susceptible crops prior to harvest. In maize production, the host resistance strategy has gained prominence because of advances in the identification of natural resistance traits. However, native resistance in maize to aflatoxin contamination is polygenic and complex and, therefore, markers need to be identified to facilitate the transfer of resistance traits into agronomically viable genetic backgrounds while limiting the transfer of undesirable traits. Unlike maize, there are no known cotton varieties that demonstrate enhanced resistance to A. flavus infection and aflatoxin contamination. For this reason, transgenic approaches are being undertaken in cotton that utilize genes encoding antifungal/anti-aflatoxin factors from maize and other sources to counter fungal infection and toxin production. This review will present information on preharvest control strategies that utilize both breeding and native resistance identification approaches in maize as well as transgenic approaches in cotton. PMID- 22069735 TI - Immunotoxins and other conjugates containing saporin-s6 for cancer therapy. AB - Ribosome-inactivating proteins (RIPs) are a family of plant toxins that permanently damage ribosomes and possibly other cellular substrates, thus causing cell death. RIPs are mostly divided in two types: Type 1 RIPs that are single chain enzymatic proteins, and type 2 RIPs that consist of an active A chain (similar to a type 1 RIP) linked to a B chain with lectin properties. RIP containing conjugates have been used in many experimental strategies against cancer cells, often showing great efficacy in clinical trials. Saporin-S6, a type 1 RIP extracted from Saponaria officinalis L. seeds, has been extensively utilized to construct anti-cancer conjugates because of its high enzymatic activity, stability and resistance to conjugation procedures, resulting in the efficient killing of target cells. This review summarizes saporin-S6-containing conjugates and their application in cancer therapy, considering in-vitro and in vivo studies both in animal models and in clinical trials. The review is structured on the basis of the targeting of hematological versus solid tumors and on the antigen recognized on the cell surface. PMID- 22069736 TI - Hemodynamic effects of anthrax toxins in the rabbit model and the cardiac pathology induced by lethal toxin. AB - Anthrax lethal toxin (LeTx) and edema toxin (EdTx) have been shown to alter hemodynamics in the rodent model, while LeTx primarily is reported to induce extensive tissue pathology. However, the rodent model has limitations when used for comparison to higher organisms such as humans. The rabbit model, on the other hand, has gained recognition as a useful model for studying anthrax infection and its pathophysiological effects. In this study, we assessed the hemodynamic effects of lethal toxin (LeTx) and edema toxin (EdTx) in the rabbit model using physiologically relevant amounts of the toxins. Moreover, we further examine the pathological effects of LeTx on cardiac tissue. We intravenously injected Dutch belted rabbits with either low-dose and high-dose recombinant LeTx or a single dose of EdTx. The animals' heart rate and mean arterial pressure were continuously monitored via telemetry until either 48 or 72 h post-challenge. Additional animals challenged with LeTx were used for cardiac troponin I (cTnI) quantitation, cardiac histopathology, and echocardiography. LeTx depressed heart rate at the lower dose and mean arterial pressure (MAP) at the higher dose. EdTx, on the other hand, temporarily intensified heart rate while lowering MAP. Both doses of LeTx caused cardiac pathology with the higher dose having a more profound effect. Lastly, left-ventricular dilation due to LeTx was not apparent at the given time-points. Our study demonstrates the hemodynamic effects of anthrax toxins, as well as the pathological effects of LeTx on the heart in the rabbit model, and it provides further evidence for the toxins' direct impact on the heart. PMID- 22069737 TI - Gene expression profiling and identification of resistance genes to Aspergillus flavus infection in peanut through EST and microarray strategies. AB - Aspergillus flavus and A. parasiticus infect peanut seeds and produce aflatoxins, which are associated with various diseases in domestic animals and humans throughout the world. The most cost-effective strategy to minimize aflatoxin contamination involves the development of peanut cultivars that are resistant to fungal infection and/or aflatoxin production. To identify peanut Aspergillus interactive and peanut Aspergillus-resistance genes, we carried out a large scale peanut Expressed Sequence Tag (EST) project which we used to construct a peanut glass slide oligonucleotide microarray. The fabricated microarray represents over 40% of the protein coding genes in the peanut genome. For expression profiling, resistant and susceptible peanut cultivars were infected with a mixture of Aspergillusflavus and parasiticus spores. The subsequent microarray analysis identified 62 genes in resistant cultivars that were up-expressed in response to Aspergillus infection. In addition, we identified 22 putative Aspergillus resistance genes that were constitutively up-expressed in the resistant cultivar in comparison to the susceptible cultivar. Some of these genes were homologous to peanut, corn, and soybean genes that were previously shown to confer resistance to fungal infection. This study is a first step towards a comprehensive genome scale platform for developing Aspergillus-resistant peanut cultivars through targeted marker-assisted breeding and genetic engineering. PMID- 22069738 TI - A public platform for the verification of the phenotypic effect of candidate genes for resistance to aflatoxin accumulation and Aspergillus flavus infection in maize. AB - A public candidate gene testing pipeline for resistance to aflatoxin accumulation or Aspergillus flavus infection in maize is presented here. The pipeline consists of steps for identifying, testing, and verifying the association of selected maize gene sequences with resistance under field conditions. Resources include a database of genetic and protein sequences associated with the reduction in aflatoxin contamination from previous studies; eight diverse inbred maize lines for polymorphism identification within any maize gene sequence; four Quantitative Trait Loci (QTL) mapping populations and one association mapping panel, all phenotyped for aflatoxin accumulation resistance and associated phenotypes; and capacity for Insertion/Deletion (InDel) and SNP genotyping in the population(s) for mapping. To date, ten genes have been identified as possible candidate genes and put through the candidate gene testing pipeline, and results are presented here to demonstrate the utility of the pipeline. PMID- 22069739 TI - Transcriptional profiles uncover Aspergillus flavus-induced resistance in maize kernels. AB - Aflatoxin contamination caused by the opportunistic pathogen A. flavus is a major concern in maize production prior to harvest and through storage. Previous studies have highlighted the constitutive production of proteins involved in maize kernel resistance against A. flavus' infection. However, little is known about induced resistance nor about defense gene expression and regulation in kernels. In this study, maize oligonucleotide arrays and a pair of closely related maize lines varying in aflatoxin accumulation were used to reveal the gene expression network in imbibed mature kernels in response to A. flavus' challenge. Inoculated kernels were incubated 72 h via the laboratory-based Kernel Screening Assay (KSA), which highlights kernel responses to fungal challenge. Gene expression profiling detected 6955 genes in resistant and 6565 genes in susceptible controls; 214 genes induced in resistant and 2159 genes induced in susceptible inoculated kernels. Defense related and regulation related genes were identified in both treatments. Comparisons between the resistant and susceptible lines indicate differences in the gene expression network which may enhance our understanding of the maize-A. flavus interaction. PMID- 22069740 TI - Ricin trafficking in plant and mammalian cells. AB - Ricin is a heterodimeric plant protein that is potently toxic to mammalian and many other eukaryotic cells. It is synthesized and stored in the endosperm cells of maturing Ricinus communis seeds (castor beans). The ricin family has two major members, both, lectins, collectively known as Ricinus communis agglutinin ll (ricin) and Ricinus communis agglutinin l (RCA). These proteins are stored in vacuoles within the endosperm cells of mature Ricinus seeds and they are rapidly broken down by hydrolysis during the early stages of post-germinative growth. Both ricin and RCA traffic within the plant cell from their site of synthesis to the storage vacuoles, and when they intoxicate mammalian cells they traffic from outside the cell to their site of action. In this review we will consider both of these trafficking routes. PMID- 22069741 TI - Trichothecenes: from simple to complex mycotoxins. AB - As the world's population grows, access to a safe food supply will continue to be a global priority. In recent years, the world has experienced an increase in mycotoxin contamination of grains due to climatic and agronomic changes that encourage fungal growth during cultivation. A number of the molds that are plant pathogens produce trichothecene mycotoxins, which are known to cause serious human and animal toxicoses. This review covers the types of trichothecenes, their complexity, and proposed biosynthetic pathways of trichothecenes. PMID- 22069742 TI - Comparative (1)H NMR metabolomic urinalysis of people diagnosed with Balkan endemic nephropathy, and healthy subjects, in Romania and Bulgaria: a pilot study. AB - (1)H NMR spectroscopy of urine has been applied to exploring metabolomic differences between people diagnosed with Balkan endemic nephropathy (BEN), and treated by haemodialysis, and those without overt renal disease in Romania and Bulgaria. Convenience sampling was made from patients receiving haemodialysis in hospital and healthy controls in their village. Principal component analysis clustered healthy controls from both countries together. Bulgarian BEN patients clustered separately from controls, though in the same space. However, Romanian BEN patients not only also clustered away from controls but also clustered separately from the BEN patients in Bulgaria. Notably, the urinary metabolomic data of two people sampled as Romanian controls clustered within the Romanian BEN group. One of these had been suspected of incipient symptoms of BEN at the time of selection as a 'healthy' control. This implies, at first sight, that metabolomic analysis can be predictive of impending morbidity before conventional criteria can diagnose BEN. Separate clustering of BEN patients from Romania and Bulgaria could indicate difference in aetiology of this particular silent renal atrophy in different geographic foci across the Balkans. PMID- 22069743 TI - Adapting yeast as model to study ricin toxin a uptake and trafficking. AB - The plant A/B toxin ricin represents a heterodimeric glycoprotein belonging to the family of ribosome inactivating proteins, RIPs. Its toxicity towards eukaryotic cells results from the depurination of 28S rRNA due to the N glycosidic activity of ricin toxin A chain, RTA. Since the extention of RTA by a mammalian-specific endoplasmic reticulum (ER) retention signal (KDEL) significantly increases RTA in vivo toxicity against mammalian cells, we here analyzed the phenotypic effect of RTA carrying the yeast-specific ER retention motif HDEL. Interestingly, such a toxin (RTA(HDEL)) showed a similar cytotoxic effect on yeast as a corresponding RTA(KDEL) variant on HeLa cells. Furthermore, we established a powerful yeast bioassay for RTA in vivo uptake and trafficking which is based on the measurement of dissolved oxygen in toxin-treated spheroplast cultures of S. cerevisiae. We show that yeast spheroplasts are highly sensitive against external applied RTA and further demonstrate that its toxicity is greatly enhanced by replacing the C-terminal KDEL motif by HDEL. Based on the RTA resistant phenotype seen in yeast knock-out mutants defective in early steps of endocytosis (?end3) and/or in RTA depurination activity on 28S rRNA (?rpl12B) we feel that the yeast-based bioassay described in this study is a powerful tool to dissect intracellular A/B toxin transport from the plasma membrane through the endosomal compartment to the ER. PMID- 22069745 TI - G(i/o) protein-dependent and -independent actions of Pertussis Toxin (PTX). AB - Pertussis toxin (PTX) is a typical A-B toxin. The A-protomer (S1 subunit) exhibits ADP-ribosyltransferase activity. The B-oligomer consists of four subunits (S2 to S5) and binds extracellular molecules that allow the toxin to enter the cells. The A-protomer ADP-ribosylates the alpha subunits of heterotrimeric G(i/o) proteins, resulting in the receptors being uncoupled from the G(i/o) proteins. The B-oligomer binds proteins expressed on the cell surface, such as Toll-like receptor 4, and activates an intracellular signal transduction cascade. Thus, PTX modifies cellular responses by at least two different signaling pathways; ADP-ribosylation of the Galpha(i/o) proteins by the A protomer (G(i/o) protein-dependent action) and the interaction of the B-oligomer with cell surface proteins (G(i/o) protein-independent action). PMID- 22069744 TI - Immunotoxins and anticancer drug conjugate assemblies: the role of the linkage between components. AB - Immunotoxins and antibody-drug conjugates are protein-based drugs combining a target-specific binding domain with a cytotoxic domain. Such compounds are potentially therapeutic against diseases including cancer, and several clinical trials have shown encouraging results. Although the targeted elimination of malignant cells is an elegant concept, there are numerous practical challenges that limit conjugates' therapeutic use, including inefficient cellular uptake, low cytotoxicity, and off-target effects. During the preparation of immunoconjugates by chemical synthesis, the choice of the hinge component joining the two building blocks is of paramount importance: the conjugate must remain stable in vivo but must afford efficient release of the toxic moiety when the target is reached. Vast efforts have been made, and the present article reviews strategies employed in developing immunoconjugates, focusing on the evolution of chemical linkers. PMID- 22069746 TI - Isolation and biochemical characterization of rubelase, a non-hemorrhagic elastase from Crotalus ruber ruber (Red Rattlesnake) venom. AB - A novel non-hemorrhagic basic metalloprotease, rubelase, was isolated from the venom of Crotalus ruber ruber. Rubelase hydrolyzes succinyl-L-alanyl-L-alanyl-L alanyl p-nitroanilide (STANA), a specific substrate for elastase, and the hydrolytic activity was inhibited by chelating agents. It also hydrolyzes collagen and fibrinogen. However, hemorrhagic activity was not observed. By ESI/Q TOF and MALDI/TOF mass spectrometry combined with Edman sequencing procedure, the molecular mass of rubelase was determined to be 23,266 Da. Although its primary structure was similar to rubelysin (HT-2), a hemorrhagic metalloprotease isolated from the same snake venom, the circumstances surrounding putative zinc binding domain HEXXHXXGXXH were found to be different when the three-dimensional computer models of both metalloproteases were compared. The cytotoxic effects of rubelase and rubelysin on cultured endothelial and smooth muscle cells were also different, indicating that the substitution of several amino acid residues causes the changes of active-site conformation and cell preference. PMID- 22069747 TI - Protein-bound uremic toxins: new insight from clinical studies. AB - The uremic syndrome is attributed to the progressive retention of a large number of compounds which, under normal conditions, are excreted by healthy kidneys. The compounds are called uremic toxins when they interact negatively with biological functions. The present review focuses on a specific class of molecules, namely the family of protein-bound uremic toxins. Recent experimental studies have shown that protein-bound toxins are involved not only in the progression of chronic kidney disease (CKD), but also in the generation and aggravation of cardiovascular disease. Two protein-bound uremic retention solutes, namely indoxyl sulfate and p-cresyl sulfate, have been shown to play a prominent role. However, although these two molecules belong to the same class of molecules, exert toxic effects on the cardiovascular system in experimental animals, and accumulate in the serum of patients with CKD they may have different clinical impacts in terms of cardiovascular disease and other complications. The principal aim of this review is to evaluate the effect of p-cresyl sulfate and indoxyl sulfate retention on CKD patient outcomes, based on recent clinical studies. PMID- 22069748 TI - Spatial patterns of aflatoxin levels in relation to ear-feeding insect damage in pre-harvest corn. AB - Key impediments to increased corn yield and quality in the southeastern US coastal plain region are damage by ear-feeding insects and aflatoxin contamination caused by infection of Aspergillus flavus. Key ear-feeding insects are corn earworm, Helicoverpa zea, fall armyworm, Spodoptera frugiperda, maize weevil, Sitophilus zeamais, and brown stink bug, Euschistus servus. In 2006 and 2007, aflatoxin contamination and insect damage were sampled before harvest in three 0.4-hectare corn fields using a grid sampling method. The feeding damage by each of ear/kernel-feeding insects (i.e., corn earworm/fall armyworm damage on the silk/cob, and discoloration of corn kernels by stink bugs), and maize weevil population were assessed at each grid point with five ears. The spatial distribution pattern of aflatoxin contamination was also assessed using the corn samples collected at each sampling point. Aflatoxin level was correlated to the number of maize weevils and stink bug-discolored kernels, but not closely correlated to either husk coverage or corn earworm damage. Contour maps of the maize weevil populations, stink bug-damaged kernels, and aflatoxin levels exhibited an aggregated distribution pattern with a strong edge effect on all three parameters. The separation of silk- and cob-feeding insects from kernel feeding insects, as well as chewing (i.e., the corn earworm and maize weevil) and piercing-sucking insects (i.e., the stink bugs) and their damage in relation to aflatoxin accumulation is economically important. Both theoretic and applied ramifications of this study were discussed by proposing a hypothesis on the underlying mechanisms of the aggregated distribution patterns and strong edge effect of insect damage and aflatoxin contamination, and by discussing possible management tactics for aflatoxin reduction by proper management of kernel-feeding insects. Future directions on basic and applied research related to aflatoxin contamination are also discussed. PMID- 22069749 TI - Expression profiling of non-aflatoxigenic Aspergillus parasiticus mutants obtained by 5-azacytosine treatment or serial mycelial transfer. AB - Aflatoxins are carcinogenic secondary metabolites produced by the fungi Aspergillus flavus and Aspergillus parasiticus. Previous studies found that repeated serial mycelial transfer or treatment of A. parasiticus with 5 azacytidine produced colonies with a fluffy phenotype and inability to produce aflatoxins. To understand how these treatments affect expression of genes involved in aflatoxin production and development, we carried out expressed sequence tag (EST)-based microarray assays to identify genes in treated clones that are differentially expressed compared to the wild-type. Expression of 183 genes was significantly dysregulated. Of these, 38 had at least two-fold or lower expression compared to the untreated control and only two had two-fold or higher expression. The most frequent change was downregulation of genes predicted to encode membrane-bound proteins. Based on this result we hypothesize that the treatments cause changes in the structure of cellular and organelle membranes that prevent normal development and aflatoxin biosynthesis. PMID- 22069750 TI - Incidence of Fusarium species and mycotoxins in silage maize. AB - Maize is frequently infected by the Fusarium species producing mycotoxins. Numerous investigations have focused on grain maize, but little is known about the Fusarium species in the entire plant used for silage. Furthermore, mycotoxins persist during the ensiling process and thus endanger feed safety. In the current study, we analyzed 20 Swiss silage maize samples from growers' fields for the incidence of Fusarium species and mycotoxins. The species spectrum was analyzed morphologically and mycotoxins were measured by LC-MS/MS. A pre-harvest visual disease rating showed few disease symptoms. In contrast, the infection rate of two-thirds of the harvest samples ranged from 25 to 75% and twelve different Fusarium species were isolated. The prevailing species were F. sporotrichioides, F. verticillioides and F. graminearum. No infection specificity for certain plant parts was observed. The trichothecene deoxynivalenol (DON) was found in each sample (ranging from 780 to 2990 ug kg(-1)). Other toxins detected in descending order were zearalenone, further trichothecenes (nivalenol, HT-2 and T-2 toxin, acetylated DON) and fumonisins. A generalized linear regression model containing the three cropping factors harvest date, pre-precrop and seed treatment was established, to explain DON contamination of silage maize. Based on these findings, we suggest a European-wide survey on silage maize. PMID- 22069751 TI - Enzyme-linked immunosorbent-assay for Deoxynivalenol (DON). AB - Deoxynivalenol (DON), one of the trichothecene mycotoxins, is a worldwide contaminant of wheat and barley, especially when infected by Fusarium graminearum, the causative agent of an epidemic wheat disease called Fusarium Head Blight. Because of the high risk of DON ingestion and the possibility of frequent exposure, it is important to develop a rapid and highly sensitive method for easy identification and quantification of DON in grain samples. In this study, we have developed an indirect competitive enzyme-linked immunosorbent assay (ELISA) to detect DON in wheat. We conjugated 3-O-Hemisuccinyl-DON (3HS DON) to Bovine serum albumin (BSA) and Ovalbumin (OVA), and obtained DON-specific mice antisera. The indirect competitive ELISA revealed that the optimal concentration of mice serum and the coated antigen was 1/1600 and 1/1500, respectively. The antiserum cross-reacted with the trichothecenes 3-acetyl-DON and T-2 toxin, reaching about 55.2% and 6.3%, respectively, as compared with DON. Results showed that the assay could be performed satisfactorily using an extraction buffer containing less than 15% methanol. Recovery from DON was 82-93% in grains. The linear detection range of DON in grains was between 0.01 and 100 MUg/mL. PMID- 22069752 TI - Mechanism of lethal toxin neutralization by a human monoclonal antibody specific for the PA(20) region of Bacillus anthracis protective antigen. AB - The primary immunogenic component of the currently approved anthrax vaccine is the protective antigen (PA) unit of the binary toxin system. PA-specific antibodies neutralize anthrax toxins and protect against infection. Recent research has determined that in humans, only antibodies specific for particular determinants are capable of effecting toxin neutralization, and that the neutralizing epitopes recognized by these antibodies are distributed throughout the PA monomer. The mechanisms by which the majority of these epitopes effect neutralization remain unknown. In this report we investigate the process by which a human monoclonal antibody specific for the amino-terminal domain of PA neutralizes lethal toxin in an in vitro assay of cytotoxicity, and find that it neutralizes LT by blocking the requisite cleavage of the amino-terminal 20 kD portion of the molecule (PA(20)) from the remainder of the PA monomer. We also demonstrate that the epitope recognized by this human monoclonal does not encompass the (166)RKKR(169) furin recognition sequence in domain 1 of PA. PMID- 22069753 TI - Molecular analysis of the interaction of the snake venom rhodocytin with the platelet receptor CLEC-2. AB - The Malayan pit viper, Calloselasma rhodostoma, produces a potent venom toxin, rhodocytin (aggretin) which causes platelet aggregation. Rhodocytin is a ligand for the receptor CLEC-2 on the surface of platelets. The interaction of these two molecules initiates a signaling pathway which results in platelet activation and aggregation. We have previously solved the crystal structures of CLEC-2 and of rhodocytin, and have proposed models by which tetrameric rhodocytin may interact with either two monomers of CLEC-2, or with one or two copies of dimeric CLEC-2. In the current study we use a range of approaches to analyze the molecular interfaces and dynamics involved in the models of the interaction of rhodocytin with either one or two copies of dimeric CLEC-2, and their implications for clustering of CLEC-2 on the platelet surface. PMID- 22069754 TI - Monoclonal antibody therapies against anthrax. AB - Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. It not only causes natural infection in humans but also poses a great threat as an emerging bioterror agent. The lethality of anthrax is primarily attributed to the two major virulence factors: toxins and capsule. An extensive effort has been made to generate therapeutically useful monoclonal antibodies to each of the virulence components: protective antigen (PA), lethal factor (LF) and edema factor (EF), and the capsule of B. anthracis. This review summarizes the current status of anti-anthrax mAb development and argues for the potential therapeutic advantage of a cocktail of mAbs that recognize different epitopes or different virulence factors. PMID- 22069755 TI - Population structure and genetic diversity of the Fusarium graminearum species complex. AB - The Fusarium graminearum species complex (Fg complex) consists of phylogenetically distinct species some of which cannot be discriminated based on their morphology. Their chemotypes and geographic distributions are dramatically different, and these highlight the challenges that Fusarium head blight (FHB) poses to plant disease specialists and plant breeders, thereby requiring that quarantine officials employ molecular diagnostic tools in their active surveillance programs. Molecular marker technologies play essential roles in species identification of the Fg complex, and they are being used widely to assess the genetic diversity of the clade. The utility, applicability and limitations of molecular methods for assessing the population structure and genetic diversity within the Fg complex are discussed with suitable examples. Knowledge gained from these studies will provide a baseline for monitoring changes in FHB pathogen diversity and mycotoxin potential over time, both of which are critical to the ultimate control and elimination of this economically devastating disease. PMID- 22069756 TI - Modes of action of microbially-produced phytotoxins. AB - Some of the most potent phytotoxins are synthesized by microbes. A few of these share molecular target sites with some synthetic herbicides, but many microbial toxins have unique target sites with potential for exploitation by the herbicide industry. Compounds from both non-pathogenic and pathogenic microbes are discussed. Microbial phytotoxins with modes of action the same as those of commercial herbicides and those with novel modes of action of action are covered. Examples of the compounds discussed are tentoxin, AAL-toxin, auscaulitoxin aglycone, hydantocidin, thaxtomin, and tabtoxin. PMID- 22069757 TI - Impact of the nature and size of the polymeric backbone on the ability of heterobifunctional ligands to mediate shiga toxin and serum amyloid p component ternary complex formation. AB - Inhibition of AB(5)-type bacterial toxins can be achieved by heterobifunctional ligands (BAITs) that mediate assembly of supramolecular complexes involving the toxin's pentameric cell membrane-binding subunit and an endogenous protein, serum amyloid P component, of the innate immune system. Effective in vivo protection from Shiga toxin Type 1 (Stx1) is achieved by polymer-bound, heterobifunctional inhibitors-adaptors (PolyBAITs), which exhibit prolonged half-life in circulation and by mediating formation of face-to-face SAP-AB(5) complexes, block receptor recognition sites and redirect toxins to the spleen and liver for degradation. Direct correlation between solid-phase activity and protective dose of PolyBAITs both in the cytotoxicity assay and in vivo indicate that the mechanism of protection from intoxication is inhibition of toxin binding to the host cell membrane. The polymeric scaffold influences the activity not only by clustering active binding fragments but also by sterically interfering with the supramolecular complex assembly. Thus, inhibitors based on N-(2-hydroxypropyl) methacrylamide (HPMA) show significantly lower activity than polyacrylamide-based analogs. The detrimental steric effect can partially be alleviated by extending the length of the spacer, which separates pendant ligand from the backbone, as well as extending the spacer, which spans the distance between binding moieties within each heterobifunctional ligand. Herein we report that polymer size and payload of the active ligand had moderate effects on the inhibitor's activity. PMID- 22069758 TI - Chemical and metabolic aspects of antimetabolite toxins produced by Pseudomonas syringae pathovars. AB - Pseudomonas syringae is a phytopathogenic bacterium present in a wide variety of host plants where it causes diseases with economic impact. The symptoms produced by Pseudomonas syringae include chlorosis and necrosis of plant tissues, which are caused, in part, by antimetabolite toxins. This category of toxins, which includes tabtoxin, phaseolotoxin and mangotoxin, is produced by different pathovars of Pseudomonas syringae. These toxins are small peptidic molecules that target enzymes of amino acids' biosynthetic pathways, inhibiting their activity and interfering in the general nitrogen metabolism. A general overview of the toxins' chemistry, biosynthesis, activity, virulence and potential applications will be reviewed in this work. PMID- 22069759 TI - Role of the mannose receptor (CD206) in innate immunity to ricin toxin. AB - The entry of ricin toxin into macrophages and certain other cell types in the spleen and liver results in toxin-induced inflammation, tissue damage and organ failure. It has been proposed that uptake of ricin into macrophages is facilitated by the mannose receptor (MR; CD206), a C-type lectin known to recognize the oligosaccharide side chains on ricin's A (RTA) and B (RTB) subunits. In this study, we confirmed that the MR does indeed promote ricin binding, uptake and killing of monocytes in vitro. To assess the role of MR in the pathogenesis of ricin in vivo, MR knockout (MR(-/-)) mice were challenged with the equivalent of 2.5* or 5* LD(50) of ricin by intraperitoneal injection. We found that MR(-/-) mice were significantly more susceptible to toxin-induced death than their age-matched, wild-type control counterparts. These data are consistent with a role for the MR in scavenging and degradation of ricin, not facilitating its uptake and toxicity in vivo. PMID- 22069760 TI - Modified heat-stable toxins (hSTa) of enterotoxigenic Escherichia coli lose toxicity but display antigenicity after being genetically fused to heat-labile toxoid LT(R192G). AB - Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrhea in humans and animals. Heat-stable (STa) and heat-labile (LT) enterotoxins produced by ETEC disrupt fluid homeostasis in host small intestinal epithelial cells and cause fluid and electrolyte hyper-secretion that leads to diarrhea. ETEC strains producing STa or LT are sufficiently virulent to cause diarrhea, therefore STa and LT antigens must be included in ETEC vaccines. However, potent toxicity and poor immunogenicity (of STa) prevent them from being directly applied as vaccine components. While LT toxoids, especially LT(R192G), being used in vaccine development, STa toxoids have not been included. A recent study (IAI, 78:316-325) demonstrated porcine-type STa toxoids [pSTa(P12F) and pSTa(A13Q)] elicited protective anti-STa antibodies after being fused to a porcine-type LT toxoid [pLT(R192G)]. In this study, we substituted the 8th, 9th, 16th, or the 17th amino acid of a human-type STa (hSTa) and generated 28 modified STa peptides. We tested each STa peptide for toxicity and structure integrity, and found nearly all modified STa proteins showed structure alteration and toxicity reduction. Based on structure similarity and toxic activity, three modified STa peptides: STa(E8A), STa(T16Q) and STa(G17S), were selected to construct LT(192)-STa( toxoid) fusions. Constructed fusions were used to immunize mice, and immunized mice developed anti-STa antibodies. Results from this study provide useful information in developing toxoid vaccines against ETEC diarrhea. PMID- 22069762 TI - The potential contributions of lethal and edema toxins to the pathogenesis of anthrax associated shock. AB - Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectional drug use form of disease in the UK and Germany have been associated with relatively high mortality rates. One notable aspect of these cases has been the difficulty in supporting patients once shock has developed. Anthrax bacilli produce several different components which likely contribute to this shock. Growing evidence indicates that both major anthrax toxins may produce substantial cardiovascular dysfunction. Lethal toxin (LT) can alter peripheral vascular function; it also has direct myocardial depressant effects. Edema toxin (ET) may have even more pronounced peripheral vascular effects than LT, including the ability to interfere with the actions of conventional vasopressors. Additionally, ET also appears capable of interfering with renal sodium and water retention. Importantly, the two toxins exert their actions via quite different mechanisms and therefore have the potential to worsen shock and outcome in an additive fashion. Finally, both toxins have the ability to inhibit host defense and microbial clearance, possibly contributing to the very high bacterial loads noted in patients dying with anthrax. This last point is clinically relevant since emerging data has begun to implicate other bacterial components such as anthrax cell wall in the shock and organ injury observed with infection. Taken together, accumulating evidence regarding the potential contribution of LT and ET to anthrax-associated shock supports efforts to develop adjunctive therapies that target both toxins in patients with progressive shock. PMID- 22069761 TI - Passive and active vaccination strategies to prevent ricin poisoning. AB - Ricin toxin (RT) is derived from castor beans, produced by the plant Ricinus communis. RT and its toxic A chain (RTA) have been used therapeutically to arm ligands that target disease-causing cells. In most cases these ligands are cell binding monoclonal antibodies (MAbs). These ligand-toxin conjugates or immunotoxins (ITs) have shown success in clinical trials [1]. Ricin is also of concern in biodefense and has been classified by the CDC as a Class B biothreat. Virtually all reports of RT poisoning have been due to ingestion of castor beans, since they grow abundantly throughout the world and are readily available. RT is easily purified and stable, and is not difficult to weaponize. RT must be considered during any "white powder" incident and there have been documented cases of its use in espionage [2,3]. The clinical syndrome resulting from ricin intoxication is dependent upon the route of exposure. Countermeasures to prevent ricin poisoning are being developed and their use will depend upon whether military or civilian populations are at risk of exposure. In this review we will discuss ricin toxin, its cellular mode of action, the clinical syndromes that occur following exposure and the development of pre- and post-exposure approaches to prevent of intoxication. PMID- 22069763 TI - Role of phospholipase A(2) in retrograde transport of ricin. AB - Ricin is a protein toxin classified as a bioterror agent, for which there are no known treatment options available after intoxication. It is composed of an enzymatically active A-chain connected by a disulfide bond to a cell binding B chain. After internalization by endocytosis, ricin is transported retrogradely to the Golgi and ER, from where the ricin A-chain is translocated to the cytosol where it inhibits protein synthesis and thus induces cell death. We have identified cytoplasmic phospholipase A(2) (PLA(2)) as an important factor in ricin retrograde transport. Inhibition of PLA(2) protects against ricin challenge, however the toxin can still be endocytosed and transported to the Golgi. Interestingly, ricin transport from the Golgi to the ER is strongly impaired in response to PLA(2) inhibition. Confocal microscopy analysis shows that ricin is still colocalized with the trans-Golgi marker TGN46 in the presence of PLA(2) inhibitor, but less is colocalized with the cis-Golgi marker GM130. We propose that PLA(2) inhibition results in impaired ricin transport through the Golgi stack, thus preventing it from reaching the ER. Consequently, ricin cannot be translocated to the cytosol to exert its toxic action. PMID- 22069764 TI - Overexpression of the Trichoderma brevicompactum tri5 gene: effect on the expression of the trichodermin biosynthetic genes and on tomato seedlings. AB - Trichoderma brevicompactum IBT 40841 produces trichodermin, a trichothecene-type toxin that shares most of the steps of its biosynthesis with harzianum A, another trichothecene produced by several Trichoderma species. The first specific step in the trichothecene biosynthesis is carried out by a terpene cylcase, trichodiene synthase, that catalyzes the conversion of farnesyl pyrophosphate to trichodiene and that is encoded by the tri5 gene. Overexpression of tri5 resulted in increased levels of trichodermin production, but also in an increase in tyrosol and hydroxytyrosol production, two antioxidant compounds that may play a regulatory role in trichothecene biosynthesis, and also in a higher expression of three trichothecene genes, tri4, tri6 and tri10, and of the erg1 gene, which participates in the synthesis of triterpenes. The effect of tri5 overexpression on tomato seedling disease response was also studied. PMID- 22069765 TI - Tacit consent: the Church and birth control in northern Italy. AB - This article employs novel documentation to examine ways in which the Church's moral rules on contraception were (or were not) communicated to parishioners in a predominantly Catholic context in a period of rapid fertility decline: the diocese of Padua, in the northeastern Italian region of Veneto, during the first half of the twentieth century. The account is based on documents that have until now been overlooked: the moral cases discussed during the periodic meetings among Padua priests in the years 1916-58, and the written answers provided by priests in response to a question asked of them concerning their efforts to combat the limiting of births. This documentation reveals the limited effect on the reproductive behavior of the position of the Catholic Church against birth control. PMID- 22069766 TI - Human smuggling in Austria: a comparative analysis of data on smuggled migrants from former Yugoslavia and the Russian Federation. AB - This article provides a summary of the author's research on human smuggling in Austria comparing migrants from Former Yugoslavia and the Russian Federation. The project's primary intent was to collect more detailed information on migrants seeking asylum in Austria and their use of smuggling services to leave their home countries, including detailed information on demographics, force or threat of force by smugglers, routes and methods of transportation, costs of smuggling, payment methods, and deeper perceptual questions regarding the flight. Another central premise of the article discusses how current distinctions between human smuggling and human trafficking are arbitrary in many regards. PMID- 22069767 TI - "Foreign brides" meet ethnic politics in Taiwan. AB - A great number of women from China, Vietnam, and Indonesia recently arrived in Taiwan to marry men of lower social strata. Such an unusual pattern of migration has stimulated debates about the status and the citizenship of the new arrivals. This study analyzes Taiwanese responses toward these marriage migrants by using a national survey conducted in 2004. Three aspects of restrictive attitudes were tapped concerning these newcomers: (1) rights to work; (2) access to public health insurance; and (3) full citizenship. Immigrants from China were most opposed, compared to women with other origins (Southeast Asia, Japan, Europe, and the US). The seemingly unrelated regression estimation regression results do not support the split labor market hypotheses, as marriage migrants do not appear to be economic threats toward members of the lower classes. In contrast, ethnic nationalism plays a key role in determining the natives' restrictive attitudes. The case of Taiwan represents a special genre, where ethnic politics selectively arouses the social rejection of women immigrants of certain origins. PMID- 22069768 TI - Partner selection and divorce in ethnic minorities: distinguishing between two types of ethnic homogamous marriages. AB - This article compares divorce risks according to marriage type. The common dichotomy between ethnic homogamous and ethnic heterogamous marriages is further elaborated by differentiating a third marriage type; ethnic homogamous marriages between individuals from an ethnic minority group and a partner from the country of origin. Based on the analysis of data concerning the Turkish and Moroccan minorities in Belgium, it has been confirmed that the divorce risk associated with these marriages is higher than that of other ethnic homogamous marriages. However, specific divorce patterns according to marriage type also indicate the importance of differences between the minority groups. PMID- 22069769 TI - Cultural dissimilarity and intermarriage. a longitudinal study of immigrants in Sweden, 1990-2005. AB - Intermarriage with natives is a key indicator of immigrant integration. This article studies intermarriage for 138 immigrant groups in Sweden, using longitudinal individual level data. It shows great variation in marriage patterns across immigrant populations, ranging from over 70 percent endogamy in some immigrants groups to below 5 percent in other groups. Although part of this variation is explained by human capital and the structure of the marriage market, cultural factors (values, religion, and language) play an important role as well. Immigrants from culturally more dissimilar countries are less likely to intermarry with natives, and instead more prone to endogamy. PMID- 22069770 TI - Decoupling migration effects from income effects on reproduction in Central American migrant-sending households. AB - Contemporary data for three Central American countries (Costa Rica, Guatemala, and Nicaragua) surveyed by the Latin American Migration Project were analyzed to determine if migration length and remittance transfers had an influence on fertility. The analysis was structured to separate societal influences on fertility attributable to migration from the income effects associated with remittance transfers. At the couple level, the odds that a birth would occur were negatively associated with an increase in U.S. remittance receipts and an increase in a wife's migration duration. However, no correlation was found between length of male migration and couple fertility. PMID- 22069772 TI - Contextualizing ethnic educational inequality: the role of stability and quality of neighborhoods and ethnic density in second-generation attainment. AB - This study examines the joint impact of neighborhood structure and ethnic density on the educational attainment of the second generation. Using second-generation samples and a majority reference sample from the Belgian Census, multi-level analysis yields the expected positive effects of neighborhood stability and quality and ethnic density on second-generation school completion. Reflecting the ethnic stratification of the Belgian housing market, majority residential concentration tends to coincide with high neighborhood stability and quality and high completion rates, whereas Moroccan concentrations overlap with low neighborhood quality, and low completion rates. For the Turkish and Italian second generation, neighborhood structure moderates ethnic density effects on school completion, in line with segmented assimilation. Our findings suggest distinct Moroccan, Turkish and Italian incorporation modes which reflect differential access to, and investments in ethnic versus mainstream social networks. PMID- 22069771 TI - The educational legacy of unauthorized migration: comparisons across U.S. immigrant groups in how parents' status affects their offspring. AB - This research compares several national-origin groups in terms of how parents' entry, legalization and naturalization (i.e., membership) statuses relate to their children's educational attainment. In the case of Asian groups, the members of which predominantly come to the United States as permanent legal migrants, we hypothesize (1) that father's and mother's statuses will be relatively homogenous and few in number and (2) that these will exert minimal net effects on second generation attainment. For Mexicans, many of whom initially come as temporary unauthorized migrants, we hypothesize (1) that parental status combinations will be heterogeneous and greater in number and (2) that marginal membership statuses will exert negative net effects on education in the second generation. To assess these ideas, we analyze unique intergenerational data from Los Angeles on the young adult members of second-generation national-origin groups and their parents. The findings show that Asian immigrant groups almost universally exhibit similar father-mother migration statuses and high educational attainment among children. By contrast, Mexicans manifest more numerous discrepant father-mother combinations, with those in which the mother remains unauthorized carrying negative implications for children's schooling. The paper discusses the theoretical and policy implications of the delays in incorporation that result from Mexican Americans needing extra time and resources compared to the members of other groups to overcome their handicap of marginal membership status (i.e., being more likely to enter and remain unauthorized). PMID- 22069773 TI - Cognitive and language skills of Turkish children in Germany: a comparison of the second and third generation and mixed generational groups. AB - The paper compares several generational groups of Turkish children in Germany with respect to cognitive skills and German language skills at an early age. Empirically, children of inter-marriages outperform the other groups of Turkish children in both tests while children with a first generation mother and a second generation father score worse than all others. All group differences regarding children's cognitive skills can be explained by the families' socio-economic status and educational resources. In contrast, with respect to children's language skills also parents' endowment with receiving country specific resources (e.g., parental German language proficiency) needs to be taken into account. PMID- 22069774 TI - Acquisition of cross-ethnic friends by recent immigrants in Canada: a longitudinal approach. AB - This paper examines the development of inter-ethnic friendships between immigrants and Canadians. It uses longitudinal data from three waves of the Canadian LSIC survey, in which newly arrived immigrants were followed during the first 4 years of settlement. It is found that pre-migration characteristics play an important role in the development of inter-ethnic friendships: immigrants who arrive at a younger age and for economic reasons, as well as those who are highly educated and have a cross-ethnic partner at the moment of arrival, establish more inter-ethnic friendships over time. In addition, post-migration characteristics affect the formation of inter-ethnic friendships. Such friendships are more common among immigrants who embrace Canadian traditions and acquire the host country language, as well as among those who work in international settings and inhabit ethnically mixed neighborhoods. The effects of pre-migration characteristics are partially mediated by post-migration characteristics. Our findings point out that economic, cultural, and spatial integration are all conducive to inter-ethnic friendships. PMID- 22069775 TI - Early influences on mammary gland development, with Suzanne Fenton. Interview by Ashley Ahearn. PMID- 22069776 TI - Planting healthier indoor air. PMID- 22069777 TI - Fukushima health study launched. PMID- 22069779 TI - Advising parents in the face of scientific uncertainty: an environmental health dilemma. PMID- 22069778 TI - Stress-pollution interactions: an emerging issue in children's health research. PMID- 22069780 TI - Indoor PM pollution and elevated blood pressure: cardiovascular impact of indoor biomass burning. PMID- 22069781 TI - Children's exposure to PBDEs: binational comparison highlights dramatic differences. PMID- 22069782 TI - Hard ride: traffic-related pollution may alter heart function in urban cyclists. PMID- 22069783 TI - Pregnancy pause: extreme heat linked to shortened gestation. PMID- 22069784 TI - Abstracts of the 136th Annual Meeting of the American Neurological Association. September 25-27, 2011. San Diego, California, USA. PMID- 22069785 TI - [In discussion today: Prof. Klaus Hergan of the University Institute for Radiology in Salzburg (interview by Dr. Eva Maria Thiel)]. PMID- 22069786 TI - Abstracts of the 21st ECCMID (European Society of Clinical Microbiology and Infectious Diseases)/27th ICC. Milan, Italy. May 7-10, 2011. PMID- 22069787 TI - [A broad portfolio of different topics. Prof. Hermann Helmberger, President of the 93rd German Roentgen Congress (interview by Florian Schneider)]. PMID- 22069788 TI - [Cooperation between radiologists and hospitals - legal requirements in forming cooperation contracts - contract physician, consultant physician, attending physician and cooperating physician]. PMID- 22069789 TI - Walter Hess-Nobel Prize for work on the brain. PMID- 22069790 TI - Abstracts of the 16th Congress of the Asian Pacific Society of Respirology. November 3-6, 2011. Shanghai, China. PMID- 22069791 TI - Abstracts of the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. October 19-22, 2011. Amsterdam, The Netherlands. PMID- 22069793 TI - Policy entrepreneurship in the development of public sector strategy: the case of London health reform. AB - The development of health policy is recognized as complex; however, there has been little development of the role of agency in this process. Kingdon developed the concept of policy entrepreneur (PE) within his 'windows' model. He argued inter-related 'policy streams' must coincide for important issues to become addressed. The conjoining of these streams may be aided by a policy entrepreneur. We contribute by clarifying the role of the policy entrepreneur and highlighting the translational processes of key actors in creating and aligning policy windows. We analyse the work in London of Professor Sir Ara Darzi as a policy entrepreneur. An important aspect of Darzi's approach was to align a number of important institutional networks to conjoin related problems. Our findings highlight how a policy entrepreneur not only opens policy windows but also yokes together a network to make policy agendas happen. Our contribution reveals the role of clinical leadership in health reform. PMID- 22069792 TI - Arbuscular mycorrhizal fungi alter the response of growth and nutrient uptake of snap bean (Phaseolus vulgaris L.) to O3. AB - The effects of arbuscular mycorrhizal fungi (AMF) Glomus mosseae on the responses to elevated O3 in growth and nutrition of snap bean (Phaseolus vulgaris L. cv Guangzhouyuan) were investigated. Exposure was conducted in growth chambers by using three O3 concentrations (20 (CF), 80 (CFO1) and 120 nL/L (CFO2); 8 hr/day for 75 days). Results showed that elevated O3 slightly impacted overall mycorrhizal colonization, but significantly decreased the proportional frequency of hypha and increased the proportional frequency of spores and vesicles, suggesting that O3 had significant effects on mycorrhizal structure. Elevated O3 significantly decreased yield, dry mass and nutrient contents (N, P, K, Ca and Mg) in both non-mycorrhizal and mycorrhizal plants. However, significant interactive effects were found in most variables due to that the reduction by O3 in the mycorrhizal plants was less than that in the non-mycorrhizal plants. Additionally, AMF increased thoe concentrations of N, P, Ca, and Mg in shoot and root. It can be concluded that AMF alleviated detrimental effects of increasing O3 on host plant through improving plant nutrition and growth. PMID- 22069794 TI - Coordination processes and outcomes in the public service: the challenge of inter organizational food safety coordination in Norway. AB - In 2004 Norway implemented a food safety reform programme aimed at enhancing inter-organizational coordination processes and outcomes. Has this programme affected inter-organizational coordination processes and outcomes, both vertically and horizontally - and if so how? This article employs the concept of inter-organizational coordination as an analytical tool, examining it in the light of two theoretical perspectives and coupling it with the empirical findings. The argument presented is that the chances of strong coordination outcomes may increase if inter-organizational processes feature a clear division of labour, arenas for coordination, active leadership, a lack of major conflicting goals, and shared obligations. PMID- 22069796 TI - The National Right to Life Committee: its founding, its history, and the emergence of the pro-life movement prior to Roe v. Wade. AB - During the mid-1960s a few Catholic journals and individuals advised that a more active role should be taken in defeating abortion reform. In 1967 the National Conference of Catholic Bishops selected James Thomas McHugh, administrator of the United States Catholic Conference's Family Life Bureau, to guide its National Right to Life Committee (NRLC). Several pro-life organizations, including Minnesota Citizens Concerned for Life, emerged and affiliated with the NRLC national office. To appeal to a more broad-based, nonsectarian movement, key Minnesota leaders proposed an organizational model that would separate the NRLC from its founder. In early 1973 McHugh and his executive assistant, Michael Taylor, proposed a different plan, facilitating the NRLC's move to independence. PMID- 22069795 TI - Body, gender, and disease: the female breast in late imperial Chinese medicine. AB - This paper examines the diverse ways in which Chinese medical experts historically gendered breast disease as a female ailment. By comparing representations of the female breast from the "Imperially-Compiled Golden Mirror of Medical Learning (Yuzuan yizong jinjian, 1742)" to those from earlier and contemporary texts, this paper analyzes how breast disease was alternately categorized as an ailment of childbearing and as a disease rooted in pathological female emotion. Medical awareness of breast disease in men did somewhat challenge these connections between womanhood and disease. Nevertheless, medical illustrations of women helped to reinforce the idea that breast disease was a characteristically female problem. PMID- 22069797 TI - "Living monuments": Union veteran amputees and the embodied memory of the Civil War. PMID- 22069798 TI - D'Eichthal and Urbain's "Lettres sur la race noire et la race blanche": race, gender, and reconciliation after slave emancipation. AB - This article is a close reading of Gustave D'Eichthal and Ishmayl Urbain's Lettres sur la race noire et la race blanche (1839), written during the decade prior to the "second" French emancipation in 1848. The article argues that the hierarchical gendering of race described in the letters is reflective of metropolitan concerns about potential for social disorder accompanying slave emancipation in the French colonies. In arguing for social reconciliation through interracial marriage and its offspring, the symbolically charged figure of the mulatto, the authors deployed gendered and familial language to describe a stable post-emancipation society. PMID- 22069799 TI - Physiological fictions and the fin-de-siecle female brain. AB - An important area of French medical research in the first half of the nineteenth century was the supposedly anomalous, sensation-based functioning of the female brain (Drs. Voisin, Virey, Brachet, Briquet). This paper explores the late century resurgence of such theory around the question of whether women could support an intense advanced education. It examines the conflicted attitudes of four females, the novelists Rachilde, Georges de Peyrebrune and Daniel Lesuer, and a medical doctor, Georgette Dega, as they tried to resist or rationalize the dogma that saw the female as a mentally diminished male. The juxtaposition of medical and fictional texts demonstrates that the so-called "automatic" functioning of the female brain led to her being embodied, in the male mind, as a symbol of the dreaded unconscious. PMID- 22069800 TI - Industrious peasants in east and west: markets, technology, and family structure in Japanese and Western European agriculture. AB - Jan de Vries engages with Osamu Saito's discussion of Tokugawa Japan, in particular, his exploration of de Vries's concept of an industrious revolution for East Asia, which was published in this journal in 2010. The discussion bears on the ongoing debate over the timing and character of the Great Divergence, when advanced parts of Europe pulled ahead of Asia. de Vries argues that the constraint on the Japanese rural household to acquire and shed labour delayed the shift from supply-side industriousness to demand-motivated industriousness, which in turn meant that the Great Divergence was already in place before 1800. PMID- 22069801 TI - Climate change, conflict and development in Sudan: global neo-Malthusian narratives and local power struggles. AB - Dystopian accounts of climate change posit that it will lead to more conflict, causing state failure and mass population movements. Yet these narratives are both theoretically and empirically problematic: the conflict-environment hypothesis merges a global securitization agenda with local manipulations of Northern fears about the state of planetary ecology. Sudan has experienced how damaging this fusion of wishful thinking, power politics and top-down development can be. In the 1970s, global resource scarcity concerns were used locally to impose the fata morgana of Sudan as an Arab-African breadbasket: in the name of development, violent evictions of local communities contributed to Sudan's second civil war and associated famines. Today, Darfur has been labelled 'the world's first climate change conflict', masking the long-term political-economic dynamics and Sudanese agency underpinning the crisis. Simultaneously, the global food crisis is instrumentalized to launch a dam programme and agricultural revival that claim to be African answers to resource scarcity. The winners, however, are Sudan's globalized Islamist elites and foreign investors, whilst the livelihoods of local communities are undermined. Important links exist between climatic developments and security, but global Malthusian narratives about state failure and conflict are dangerously susceptible to manipulations by national elites; the practical outcomes decrease rather than increase human security. In the climate change era, the breakdown of institutions and associated violence is often not an unfortunate failure of the old system due to environmental shock, but a strategy of elites in wider processes of power and wealth accumulation and contestation. PMID- 22069802 TI - Navigating the AIDS industry: being poor and positive in Tanzania. AB - This article shows how poor people living with HIV/AIDS in Tanzania navigate a myriad of actors, agencies and organizations to obtain the aid they need to survive. It focuses on community-based organizations which establish networks of care through which people obtain care, treatment and financial support. A case study of a roadside town in Tanzania illustrates that these community-based networks of care - essential to the survival of many - are partly the product of the AIDS industry, which encourages the establishment of community-based organizations and voluntary service delivery rather than more formalized systems of care. Community-based organizations, however, are so poorly supported that they often deploy self-destructive strategies. The need to strategically navigate the AIDS industry creates tension and even conflict among HIV-positive activists, the people they represent and the wider community, which undermines rather than strengthens community-based interventions. Whilst the AIDS industry promises inclusion of HIV-positive people in the response to HIV/AIDS, it succeeds only partially, with the result that it may potentially do more harm than good. PMID- 22069803 TI - Abortion law reforms in Colombia and Nicaragua: issue networks and opportunity contexts. AB - This article analyses two instances of abortion law reform in Latin America. In 2006, after a decades-long impasse, the highly controversial issue of abortion came to dominate the political agenda when Colombia liberalized its abortion law and Nicaragua adopted a total ban on abortion. The article analyses the central actors in the reform processes, their strategies and the opportunity contexts. Drawing on Htun's (2003) framework, it examines why these processes concluded with opposing legislative outcomes. The authors argue for the need to understand the state as a non-unitary site of politics and policy, and for judicial processes to be seen as a key variable in facilitating gender policy reforms in Latin America. In addition, they argue that 'windows of opportunity' such as the timing of elections can be critically important in legislative change processes. PMID- 22069804 TI - The spatial pattern of suicide in the US in relation to deprivation, fragmentation and rurality. AB - Analysis of geographical patterns of suicide and psychiatric morbidity has demonstrated the impact of latent ecological variables (such as deprivation, rurality). Such latent variables may be derived by conventional multivariate techniques from sets of observed indices (for example, by principal components), by composite variable methods or by methods which explicitly consider the spatial framework of areas and, in particular, the spatial clustering of latent risks and outcomes. This article considers a latent random variable approach to explaining geographical contrasts in suicide in the US; and it develops a spatial structural equation model incorporating deprivation, social fragmentation and rurality. The approach allows for such latent spatial constructs to be correlated both within and between areas. Potential effects of area ethnic mix are also included. The model is applied to male and female suicide deaths over 2002-06 in 3142 US counties. PMID- 22069805 TI - The veterinary medicine industry in Britain in the twentieth century. AB - Economic historians have focused research effort on accounting for the growth and significance of Britain's pharmaceutical industry, but little effort has so far been directed at the veterinary medicine industry, which formed an important part of the wider sector. This article addresses that gap. Factors responsible for that sector's relative insignificance until the 1950s included a general tendency to slaughter rather than to treat sick animals, the absence of advanced medicines until the innovation of sulpha drugs and antibiotics, and difficult relations with the wider pharmaceutical industry. Thereafter output of veterinary medicines increased dramatically, arising from an exponential growth in the demand for intensively farmed poultry meat. Since the 1980s a decline in the use of drugs in agriculture has caused the industry to concentrate on the health needs of domestic animals rather than those of livestock. PMID- 22069806 TI - Infant mortality and the health of survivors: Britain, 1910-50. AB - The first half of the twentieth century saw rapid improvements in the health and height of British children. Average height and health can be related to infant mortality through a positive selection effect and a negative scarring effect. Examining town-level panel data on the heights of school children, no evidence is found for the selection effect, but there is some support for the scarring effect. The results suggest that the improvement in the disease environment, as reflected by the decline in infant mortality, increased average height by about half a centimetre per decade in the first half of the twentieth century. PMID- 22069807 TI - Becoming farmers: opening spaces for women's resource control in Calakmul, Mexico. AB - Despite empirical findings on women's varied and often extensive participation in smallholder agriculture in Latin America, their participation continues to be largely invisible. In this article, I argue that the intransigency of farming women's invisibility reflects, in part, a discursive construction of farmers as men. Through a mixture of quantitative and qualitative methods, including interviews with one hundred women in Calakmul, Mexico, I demonstrate the material implications of gendered farmer identities for women's control of resources, including land and conservation and development project resources. In particular, I relate the activities of one women's agricultural community-based organization and the members' collective adoption of transgressive identities as farmers. For these women, the process of becoming farmers resulted in increased access to and control over resources. This empirical case study illustrates the possibility of women's collective action to challenge and transform women's continued local invisibility as agricultural actors in rural Latin American spaces. PMID- 22069808 TI - Putting the market in its place: food security in three Mapuche communities in southern Chile. AB - This article analyzes the impact of state policies since the 1970s on household food security in several Mapuche communities in the Araucania region of Chile (Region IX). The author highlights key transformations in the national economy and food system and endeavors to link those to local phenomena, in particular the absorption of the local livelihood strategies and food systems into capitalist markets and the high incidences of food insecurity. The article concludes that a reconceptualization of macroeconomic and indigenous policies are required to rebuild the material and social foundations of rural Mapuche communities that provide the bases from which their inhabitants can reconstruct a mutually beneficial relationship with the broader Chilean society and avert the continued acceleration of tension and violence. PMID- 22069809 TI - Research notes from the underworld: the entry logs of the Rio de Janeiro Casa de Detencao, 1860-1969. AB - The Rio de Janeiro state archive's collection of entry logs for the city's central detention center, going back to the mid-nineteenth century, provides a rare glimpse into the lives of Rio's-and Brazil's-poor and working classes who otherwise left few written records behind. During the time when the institution maintained the entry logs, police exercised broad power to make arrests. Although relatively few detainees were ever prosecuted or even formally charged, the detention center kept detailed records of detainees' physical appearance, attire, home address, nationality, sex, affiliation, and so on, as well as information about any criminal charges. This article explores the wealth of empirical data that the entry logs provide. It also suggests how scrutinizing this type of document across time shows how record keeping itself changed, in turn affording researchers rare insight into the inner workings of modern Latin American society. PMID- 22069810 TI - One of the boys: Ammie Wilson's challenge to postwar ideals of femininity on the stock show circuit. PMID- 22069811 TI - Age of pension eligibility, gains in life expectancy, and social policy. AB - Canadians are living longer and retiring younger. When combined with the aging of the baby-boom generation, that means that the "inactive" portion of the population is increasing and there are concerns about possibly large increases in the burden of support on those who are younger. We model the impact of continued future gains in life expectancy on the size of the population that receives public pension benefits. We pay special attention to possible increases in the age of eligibility and the pension contribution rate that would maintain the publicly financed component of the retirement income security system. PMID- 22069812 TI - The redistributional impact of Canada's Employment Insurance Program, 1992-2002. AB - For a decade or so starting in the early 1990s, Canada's major income support programs underwent substantial reform. Meanwhile, the economy first lingered in a deep recession and then recovered with a period of strong growth. This paper focuses on how the distributional impact of Employment Insurance (EI) evolved during this period. We find that EI was strongly redistributive throughout the whole period with respect to the earnings of individuals, and somewhat less so for family income. But we also show that the distribution of benefits and contributions changed substantially over time, becoming less redistributive. Somewhat counter-intuitively, both the benefit and contribution sides of the program are shown to be redistributive, even though the contribution structure is regressive. These findings are relevant in the current context, as the economy struggles with a combination of high unemployment and fiscal pressures on government spending. PMID- 22069814 TI - Hopi Indian witchcraft and healing: on good, evil, and gossip. PMID- 22069813 TI - Governance and sustainability at a municipal scale: the challenge of water conservation. AB - Municipal water conservation is increasingly promoted as a key dimension of environmental sustainability at the municipal scale. Progress toward municipal water conservation in Canada has, however, been poor. This paper examines the governance dimension of water conservation, and presents evidence in support of the argument that conservation efforts on the part of water utilities (and sometimes municipalities) are often constrained by factors external to their jurisdiction. To explore these issues, this paper presents a case study of municipal water conservation in Canada. The analysis identifies governance related barriers to water conservation and explores the relationship between these barriers and broader issues stemming from the multi-scalar, fragmented nature of environmental governance in Canada. PMID- 22069815 TI - Cherokee adaptation to the landscape of the west and overcoming the loss of culturally significant plants. PMID- 22069816 TI - Blood vessel disease linked to dementia. Strategies that protect blood vessels also fight aging-related memory loss. PMID- 22069818 TI - Angioplasty via wrist artery safe, effective. U.S. doctors are turning to the radial artery for angioplasty. PMID- 22069817 TI - Ask the doctor. My 69-year-old husband has had cardiomyopathy and diabetes for several years. Lately his ankles are always swollen. At his last doctor's visit, my husband's cardiologist said his heart has leaky valves and his ejection fraction is 10%. What would be the best plan for him? PMID- 22069819 TI - The smartphone will see you now. "Apps" and devices are turning cell phones into tools for health. PMID- 22069820 TI - More to the story than alcohol=heart protection. Studies showing that alcohol protects the heart raise questions about drinking. PMID- 22069821 TI - Nature trumps nurture for heart disease. PMID- 22069823 TI - Repeat "zaps" often needed to stop atrial fibrillation. PMID- 22069822 TI - Water exercise safe for troubled hearts. PMID- 22069824 TI - Ask the doctor. I had a pacemaker implanted a few months ago. I am planning to join a gym to get back some strength in my arms and upper body, but I am afraid of damaging the wires with some of the presses and pull down movements I would have to do to work out on the gym's machines. Are there any exercises or movements I should avoid? PMID- 22069825 TI - Ask the doctor. My 61-year-old mother plans to take a long plane trip. Her legs usually become swollen when she flies a long distance. Should she wear elastic stockings or take any other precautions so she doesn't develop a blood clot in her legs? PMID- 22069826 TI - Ask the doctor. My blood pressure has wide swings each day. It can go as high as 210/110 with even minor stress like grocery shopping, then fall to 100/50, which makes me tired and needing rest. I take 15 mg of isosorbide dinitrate and a slow release nitrate for angina. I also take 10 mg of atenolol (Tenormin) to slow my heart rate. My doctor says I'm just a "reactive person." My diet is excellent, and I try to keep active. Could my adrenal glands have anything to do with this? PMID- 22069827 TI - [Reduced (bioavailability of) nitric oxide as a cause of adverse prognosis in anaemic patients]. PMID- 22069828 TI - [Comment on the article "ECG in childhood: what the cardiologist for adults should know" by Bronzetti et al]. PMID- 22069830 TI - [Remembering William B. Kannel: pioneer in cardiovascular epidemiology]. PMID- 22069831 TI - Introduction--the First IEEE Conference on Healthcare Informatics, Imaging, and Systems Biology HISB'11. PMID- 22069832 TI - The role of Reviews. Preface. PMID- 22069833 TI - "Ideal" practice helps this FP thrive. PMID- 22069834 TI - Colon cleansing: not dangerous if done right. PMID- 22069835 TI - [Progress of the clinical laboratory as applied to gynecology and obstetrics. 1956]. PMID- 22069836 TI - Louise Andreas-Salome: at the high noon of culture, in the shadows of psychoanalysis. PMID- 22069837 TI - [Contributions to the progress in Mexico of gynecological pathology. Summary of 10 years (1946-1956). 1956]. PMID- 22069838 TI - [Clinical utility of the dosage of ovarian hormones. 1956]. PMID- 22069839 TI - The 800-pound gorilla: state lawmakers are trying to cut costs so the program will survive, even when millions more are added to the rolls. PMID- 22069840 TI - The technology promise: widespread use of electronic medical records promises to transform health care. But can we afford it? PMID- 22069841 TI - Got milk? Awareness of the health benefits and cost savings of breastfeeding continues to spread. PMID- 22069842 TI - The reach of free speech: recent rulings make it tough to nail down the boundaries of protected speech and other thorny state-federal issues. PMID- 22069843 TI - Evaluation techniques for paretic vertical strabismus. AB - Vertical strabismus can be associated with paretic or restrictive causes. Paretic causes may be due to a weak muscle or paresis, or to a total lack of muscle function caused by a third, fourth or sixth cranial nerve palsy. When examining a patient with vertical strabismus, it is paramount that we differentiate between a restricted cause and paretic cause. This paper discusses the nonsurgical techniques used in evaluating paretic vertical strabismus. There are no easy methods, and evaluation techniques can vary depending on the cooperation of the patient. It is essential to look at versions and ductions, pattern strabismus, measure in all positions of gaze and evaluate torsion. We know that measuring strabismus, especially in children can be challenging. Afew different tests and techniques are discussed. A review of the literature regarding the different evaluation techniques for vertical strabismus were collated and analyzed. PMID- 22069844 TI - Management of paretic vertical deviations. AB - Paretic vertical deviations are characterized by complex patterns of incomitance that make them some of the most challenging strabismus problems to treat. Optimum results are obtained by performing surgery on those muscles, selected from among the eight cyclovertical muscles in the two eyes, that minimize the incomitance. In superior oblique paresis the additional factors of torticollis and torsion need to be addressed and aberrant regeneration can alter the surgical plan in third nerve paresis. PMID- 22069845 TI - Situational restriction: using your physical exam to differentiate pulley abnormalities from other vertical deviations secondary to restrictive conditions. AB - The description of the orbital pulley system has changed the way we understand eye movements and ocular motility disorders. The presence of abnormalities in the orbital pulley system can complicate the assessment of vertical restrictive conditions. The standard tests for restriction are reviewed. These include version and duction testing, assessing saccades, differential intraocular pressure measurements, forced duction testing, and forced generation testing. We introduce the concept of situational restriction and how to look for it during your physical exam. Situational restriction is a limitation of ocular rotation that is dependent on the path that is taken to try to arrive at a tertiary position of ocular rotation. Specifically, it shows noncommutative movement that breaks Listing's Law. The presence of situational restriction denotes that a pulley abnormality is present. PMID- 22069846 TI - Management of vertical ocular deviations secondary to restrictive conditions. AB - BACKGROUND AND PURPOSE: Management of vertical strabismus secondary to restrictive conditions can be challenging for both the patient and practitioner. The purpose of this paper is to identify both common and uncommon causes of vertical restrictive strabismus, to discuss the evaluation of these conditions, and to briefly review the etiology and recommendations for surgical management. METHOD: Current literature was reviewed as well as the surgical techniques that have been found to be most useful from experience over the past twenty years of practice. CONCLUSION: Surgical realignment and elimination of diplopia is both challenging and problematic. Surgery should be designed to relieve restriction, with attention to identifying and managing incomitance. Furthermore, it is important to establish realistic goals with patients. PMID- 22069847 TI - Vertical Deviations Secondary to Supranuclear Origins. AB - A vertical deviation is a relatively common finding in a pediatric ophthalmology and adult strabismus practice. Fortunately, vertical deviations secondary to supranuclear entities occur somewhat less frequently, given the neuro- logical implications associated with many of them. Because of the lower incidence of supranuclear vertical deviations, they can easily be overlooked or misdiagnosed if special care is not taken in its evaluation. The purpose of this paper is to assist the clinician in recognizing vertical deviations specific to supranuclear disorders, the associated findings, and the diagnostic tools geared toward them. PMID- 22069848 TI - Surgical treatment of vertical ocular motility disorders of supranuclear origin. AB - Vertical ocular motility disorders of supranuclear origin can be congenital or acquired later in life. They produce complex forms of strabismus that require specialized surgical management to restore ocular alignment, eliminate torticollis, treat diplopia, and restore normal lid position. For each condition, surgical management must be individualized to address multiple impediments to fusion. This article outlines the surgical management of three common types of supranuclear vertical strabismus. PMID- 22069849 TI - Evaluation of vertical deviations secondary to anatomical abnormalities. AB - Vertical strabismus secondary to anatomical abnormalities includes orbital anomalies leading to rotation of the extraocular muscle cone, converting the horizontal rectus muscles from adductors and abductors to elevators and depressors. Craniofacial syndromes also may include anomalous or absent muscles, simulating paretic strabismus. Abnormal musculature is also a cause of vertical strabismus. Included in this category is Brown syndrome and Duane retraction syndrome. Unusual strabismus that does not fit known patterns may be caused by anatomical anomalies. High axial myopia can lead to the "heavy eye syndrome" in which elevation is progressively more limited. Anti-elevation syndrome is caused by previous strabismus surgery, causing a Brown syndrome-like clinical picture with additional pseudo-overaction of the contralateral inferior oblique. Imaging studies are useful in determining the etiology of atypical strabismus and developing a treatment plan. PMID- 22069850 TI - Management of vertical deviations secondary to other anatomical abnormalities. AB - BACKGROUND AND PURPOSE: To review the surgical management of five vertical strabismus syndromes secondary to anatomical abnormalities. These syndromes are: 1) craniosynostosis; 2) "heavy eye syndrome" of high myopia; 3) Brown syndrome; 4) upshoot-downshoot in Duane retraction syndrome (DRS); and 5) antielevation syndrome after inferior oblique anteriorization. METHODS: The syndromes are presented from evolving to well-accepted surgical management practices based on review of the current literature. RESULTS: Surgical management techniques discussed include: 1) excyclotorsion of the muscle cones inducing elevation in adduction craniosynostosis, and surgery to stabilize the globe vertically in adduction in this situation; 2) loop myopexy to prevent prolapse of the elongated, highly myopic eye posteriorly between the superior and lateral recti; 3) superior oblique tenotomy and lengthening procedures to address inability to elevate the adducted eye in Brown syndrome; 4)Y-splitting of the lateral rectus to stabilize the adducted globe vertically in Duane retraction syndrome; and 5) re-recession of the anteriorized inferior oblique to a position posterior to the inferior rectus insertion in anti-elevation syndrome. CONCLUSIONS: The surgeon can, through careful surgical management techniques, alter the form of anatomy in these conditions and thereby provide more normally functioning binocular systems. PMID- 22069851 TI - Evaluation of vertical deviations secondary to other causes. AB - Distinguishing the cause of a vertical deviation can be important for management. When surgery is being considered, it is also critical to distinguish a true hypertropia from a dissociated vertical deviation (DVD). This paper reviews the clinical manifestations of DVD, true hypertropia, and primary oblique muscle dysfunction. PMID- 22069852 TI - Treatment of vertical deviations secondary to other causes. AB - INTRODUCTION AND PURPOSE: Surgical treatment of vertical deviations secondary to other causes can be difficult and treatment approaches may vary. The purpose of this discussion is to present surgical treatment options for the management of vertical deviations secondary to other causes including dissociated vertical deviation, primary inferior oblique overaction, superior oblique overaction, and nonspecific eccentric gaze hypertropia with diplopia. RESULTS: Surgical treatment of vertical deviations secondary to other causes is beneficial to patients. Treatment approaches may vary depending upon patient circumstances and surgeon preference. Side effects and complications from surgery to manage these conditions can occur but are usually of minor significance and not vision threatening. CONCLUSIONS: Treatment of vertical deviations secondary to other causes is effective and results usually satisfactory. PMID- 22069853 TI - Symposium: vertical strabismus: evaluating the highs and lows. PMID- 22069854 TI - A false start in the race against doping in sport: concerns with cycling's biological passport. AB - Professional cycling has suffered from a number of doping scandals. The sport's governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling's biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist's system. Instead, the biological passport tracks biological variables in a cyclist's blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports. PMID- 22069856 TI - [Guidelines, homeopathy, placebo]. PMID- 22069855 TI - [About the article: diagonal earlobe crease, clinical curiosity or ischemic cardiopathy marker?]. PMID- 22069857 TI - [Jerusalem syndrome]. PMID- 22069858 TI - Imaging vignette: scimitar syndrome. PMID- 22069859 TI - Securing today's campus. PMID- 22069860 TI - Five reasons why your people are in danger. PMID- 22069861 TI - Can sports kill you? PMID- 22069862 TI - Improving personal risk assessments. PMID- 22069863 TI - Making sense of electrical PPE. PMID- 22069864 TI - Engage to go from good to great. PMID- 22069866 TI - Banking on bipartisanship. PMID- 22069865 TI - Optimizing programs under OSHA's new initiatives. PMID- 22069867 TI - Intelligent hearing protection: a primer. PMID- 22069868 TI - Words of wisdom. PMID- 22069869 TI - Triple play. PMID- 22069870 TI - Putting real-time information to good use. PMID- 22069871 TI - Gas detection programs of the future. PMID- 22069872 TI - Little changes solve big pain problems. PMID- 22069873 TI - How to manage ergonomics champions at the grassroots level. PMID- 22069874 TI - No business like snow business. PMID- 22069875 TI - Water filtration snuffs dust hazards. PMID- 22069876 TI - Lockout/tagout today, tomorrow, and beyond. PMID- 22069877 TI - Higher leadership math. PMID- 22069878 TI - A salute to the nation's first hospice. AB - There is great honor in being the first hospice in America. This distinction belongs to The Connecticut Hospice (TCH) of Branford, Connecticut. This commendable organization was born in 1974, only two years after Elisabeth Kubler Ross, M.D. testified before the U.S. Senate Committee on Aging at the first Congressional hearings on the previously taboo subject of death and dying in America. I had the honor of helping to produce those hearings. PMID- 22069879 TI - Hospice payment reform: a look into the future. AB - This article incorporates findings from the first phase of a Hospice U-shaped Modeling Project conducted by Simione Consultants that were presented on July 14 at the 17th Annual NAHC Financial Management Conference & Exposition in San Diego, CA, by Robert Simione and Theresa M. Forster. SPECIAL NOTE: The National Association for Home Care & Hospice (NAHC) and its affiliated Hospice Association of America (HAA) extend special thanks to the agencies that volunteered to participate in the hospice payment modeling study referenced in this article, and particularly to Robert Simione, Jared Shure Michael Simione, and Kaitlyn Quada of Simione Consultants, LLC, for their significant contributions to advancing knowledge of the potential impact of hospice payment reform. PMID- 22069880 TI - Modification to hospice CAP computation: opportunities and considerations. PMID- 22069881 TI - Hospice: an evolution in end-of-life care. PMID- 22069882 TI - High tech to high touch: my journey to becoming a hospice volunteer. PMID- 22069883 TI - Nurses lead the way: bringing home the benefits of hospice. PMID- 22069884 TI - Living well at the end of life: a national conversation. PMID- 22069885 TI - Private duty's role in hospice care. PMID- 22069886 TI - Challenges intensify pressures on not-for-profit agencies. PMID- 22069887 TI - Pain: the hidden culprit behind challenging behaviors of those with Alzheimer's. PMID- 22069888 TI - Mad as hell. PMID- 22069889 TI - A tribute to Elisabeth Kubler-Ross. PMID- 22069890 TI - [Atopic thumb. Fungus? No, gameboy!]. PMID- 22069891 TI - [Consciousness disorder of unknown origin. These signs point to the diagnosis]. PMID- 22069892 TI - [Septic arthritis. Only rapid therapy saves the cartilage]. PMID- 22069893 TI - [Naturopathy consultation. Sinusitis]. PMID- 22069894 TI - [Recipe for success against warts. Keratolysis, antiviral therapy and especially motivation (interview by Dr. Judith Neumaier)]. PMID- 22069895 TI - [COPD: smoker's cough? No, life-threatening!]. PMID- 22069896 TI - [Epidemiology and diagnosis of COPD]. PMID- 22069897 TI - [Pharmacotherapy of COPD]. PMID- 22069898 TI - [Supportive measures in the management of COPD]. PMID- 22069899 TI - [Emergency checklist: Priapism]. PMID- 22069900 TI - [Methotrexate-related deaths in patients with rheumatoid arthritis]. PMID- 22069901 TI - Leading the last great civil rights battle ... PMID- 22069902 TI - Riding the age wave: how America can stay afloat and enjoy the ride. PMID- 22069904 TI - Signs of great service. PMID- 22069903 TI - Home care: a nursing adventure in caring and love. PMID- 22069905 TI - Limited restrictions equal unlimited care. PMID- 22069906 TI - Your patient with Alzheimer's is being hospitalized: how can you help? PMID- 22069907 TI - A crisis of debts and confidence: how home care can help. PMID- 22069908 TI - [Sixty years already...always a bright future before us, with you!]. PMID- 22069909 TI - [I want the process of cooperation to be simplified, better structured and more legible]. PMID- 22069910 TI - [The emancipation of nursing care over the years]. AB - The emancipation of nursing care over the years. The definition of an autonomous nursing role in 1978, professional regulations in 1993, the 2002 nursing acts decree, prescribing rights in 2007, etc., these are the significant dates in the evolution of nursing practice. At the same time, training has moved from a two year course in 1951 to a three-year university degree in 2009. PMID- 22069911 TI - [A century in which a common identity and professional recognition emerged]. AB - A century in which a common identity and professional recognition emerged. The professional history of nurses has evolved significantly, from the nun to the medical assistant with expertise in nursing care. This evolution has resulted in the recognition of an autonomous professional identity. Over the course of the last century, nursing moved from a vocation to a profession. The story continues. PMID- 22069912 TI - [The transformation of equipment for nursing care]. AB - The transformation of equipment is shaping the evolution of nursing care. The provision of nursing care and the administration of treatment prescribed by the doctor require the use of a range of medical devices and equipment. Skilled in their use, the nurse must practise medical devices vigilance. Different memories and perspectives on the recent history of equipment which has strongly influenced the evolution of nursing care. PMID- 22069913 TI - [From the disorganization of care to the support of nursing sciences]. AB - From the disorganisation of care to the support of nursing sciences. The early communal wards providing shelter for the poor led to the development of mass care. The emergence of concepts regarding the provision of care, combined with the increasing demands of patients in terms of quality and safety inspired a more individualised approach to nursing care. The evolution of determining healthcare factors will lead to new organisations within which nursing sciences will have a role to play. PMID- 22069914 TI - [Nurses' notes, a tool which reflects quality of care]. AB - Nurses' notes, a tool which reflects the quality of care. Originally, nurses passed on knowledge and actions verbally. Theorists then developed care models which emerging nursing schools taught their students. Tools for writing down and passing on information were created, refined and adapted to meet the evolutions of society. As the main thread of nursing notes, clinical reasoning guides the implementation of the care given. PMID- 22069915 TI - [Half a century history of nurses and working women]. AB - Half a century of history of nurses and working women. A historian's perspective of a professional group considers firstly the context, to understand what distinguishes it from other groups. The remarkable aspect of the history of nurses over the last half century is that they are predominantly women. It is therefore interesting to determine if the evolution of this profession and its practitioners, as noted in research, has any correlation with the history of the country's female population in general. PMID- 22069916 TI - [The evolution of initial training over the last sixty years]. AB - The evolution of initial training over the last sixty years. Nursing training, over the last sixty years, has followed the social evolutions of our country. Professionals express a strong need for recognition. The 2009 training reference framework could be expected to radically change the nursing profile. An assessment of this programme should enable us to consolidate or modify training to meet users' needs. PMID- 22069917 TI - [Nurses and nursing care research]. AB - Nurses and nursing care research. Nursing practice is fundamentally a work of creation. Unique, singular, appropriate and helpful to the patient, every act of care aims to take root in the subtle fertile soil of the nursing art. A base which, in all humility, invites caregivers to demonstrate curiosity and a critical mind with regard to their practices. At Toulouse university hospital, research into nursing care has been consolidating practices for more than fifteen years. PMID- 22069918 TI - [The different perspectives of young professionals]. AB - The different perspectives of young professionals. Young graduate nurses or nursing students, they are the future of the nursing profession. They will take up the baton in order to meet the nursing needs of today and tomorrow. They will write the next chapter in the history of their profession. Even if some are unable to project themselves into the future, having to focus on the present demands of their daily lives as caregivers, they are all clear on their motivation to provide care. PMID- 22069919 TI - [Handling a claim or complaint]. AB - Handling a claim or a complaint. Any user of a healthcare institute can lodge a complaint with the Commission for Relations with Users and Quality of Care. This organisation's mission is to inform patients or their family of their rights, to seek conciliation between different parties and to improve care within the institute. PMID- 22069920 TI - [Psychologist-nurse, a rewarding collaboration]. AB - Psychologist-nurse, a rewarding collaboration. The collaboration between nurses and psychologists is relatively recent within healthcare institutes. Gaining maximum value from such a collaboration requires solid knowledge of the roles and the limits of each profession as well as a real desire to work together, for the benefit of the greater well-being of the patient and, indirectly, of the teams. PMID- 22069921 TI - [Nurse home visits in France]. AB - Nurse home visits in France. More and more nurses carry out home visits, either as freelance nurses or employees of a nurse home visits service, a home hospital care structure or a nursing care centre. These home visits are both demanded by patients and encouraged by the health authorities. As a consequence, the service is expanding every year. PMID- 22069922 TI - A day at the emergency department. PMID- 22069923 TI - [Nursing care of the heart arrest patient]. PMID- 22069924 TI - [Psychosomatic disorders]. PMID- 22069925 TI - [Training for blood transfusions]. PMID- 22069927 TI - Defining critical safety behaviors in a point-of-view video observation study of tree fallers at work. AB - This study aimed to characterize the use of five critical safety behaviors by tree fallers at different skill levels, and to test the feasibility of using a helmet camera to observe work activities directly in a remote environment. Small cameras were mounted on standard hard-hats. Video data were obtained for pairs of fallers at four different skill levels, from beginning students to professional fallers. Critical action steps during tree episodes were coded and compared. Critical action steps for fallers were successfully distinguished during work activities. Notable differences were observed among fallers in different skill categories and between individual fallers. This study found that the helmet camera worked well for observing faller work behavior, and that point-of-view video observation may be used to evaluate student loggers and training programs. We also found that professional fallers may have been exposed to increased hazard; care should be observed with helmet cameras designed for professionals. PMID- 22069926 TI - A quantitative method for estimating dermal benzene absorption from benzene containing hydrocarbon liquids. AB - This study examines a method for estimating the dermal absorption of benzene contained in hydrocarbon liquids that contact the skin. This method applies to crude oil, gasoline, organic solvents, penetrants, and oils. The flux of benzene through occluded skin as a function of the percent vol/vol benzene in the liquid is derived by fitting a curve to experimental data; the function is supralinear at benzene concentrations < or = 5% vol/vol. When a liquid other than pure benzene is on nonoccluded skin, benzene may preferentially evaporate from the liquid, which thereby decreases the benzene flux. We present a time-averaging method here for estimating the reduced dermal flux during evaporation. Example calculations are presented for benzene at 2% vol/vol in gasoline, and for benzene at 0.1% vol/vol in a less volatile liquid. We also discuss other factors affecting dermal absorption. PMID- 22069928 TI - Association between biofuel exposure and adverse birth outcomes at high altitudes in Peru: a matched case-control study. AB - Nearly one-third of the Peruvian population burns biofuels for cooking. Similarly, approximately one-third of this population lives at high altitudes. Cooking with biofuels and living at high altitudes have been implicated in adverse perinatal outcomes. This study attempted to determine the risk of low birth weight (LBW) and/or preterm delivery in relation to biofuel use in inhabitants at high altitudes in Peru. A matched-case study was performed in two high-altitude cities. All subjects (n=190) were identified from public-hospital records. Cases were matched by hospital by week of birth and area of residence. Cases were defined as: women with an at-term but LBW newborn; or women with a preterm birth. Adjusted conditional logistic regression analyses were used to determine odds ratio. Fifty-two percent of the cases used biofuel whereas only 30% of the controls used biofuel. The use of biofuel for cooking was found to be strongly associated with increased risks of LBW, but was not significantly linked to preterm births. PMID- 22069929 TI - Exposure to lead from a storage site associated with intellectual impairment in Chilean children living nearby. AB - This study assesses the degree of impairment of children's IQ scores due to exposure to lead from a storage site. In 2005, we studied 192 children in Antofagasta, Chile, age 7-16 years who had been exposed to a lead storage site from birth until its removal in 1998. We used past (1998) and current (2005) blood lead levels as explanatory variables for IQ, which was measured once in 2005 using the WISC-r test. Multilevel mixed-effects linear regression models were constructed, adjusting for potential confounders. Current blood lead level (BPb, 2005) was associated with a significant decrease in full-scale IQ (P value = 0.03), whereas blood lead level measured in 1998 (BPb, 1998) showed an inverse but not significant association with full-scale IQ (P value = 0.35). The findings provide evidence that exposure to an open source of environmental lead can exert an effect on IQ. Policy efforts should be targeted to prevent lead exposure to avoid children's intellectual impairment. PMID- 22069930 TI - The effectiveness of using interferon-gamma release assays in screening immigration employees for latent tuberculosis infection. AB - We assessed the prevalence of latent tuberculosis infection in immigration employees and compared two of the screening methods. Using a cross-sectional study design, we administered questionnaires regarding demographics, work, medical history, and tuberculosis risk factors to employees at two immigration facilities. Participants underwent tuberculin skin test (TST) placement and blood collection for the QuantiFERON-TB Gold in-Tube (QFT-GIT) assay. Fifty-four employees underwent QFT-GIT and TST placement. All QFT-GIT results were negative, and three employees tested TST positive. Twenty-three (49%) of 47 employees requiring two-step TST testing underwent second TST placement. Return rates for first and second TST reading were 76% and 74%, respectively. The QFT-GIT completion rate was higher than that for TST (100% vs. 39%, P < 0.001). Agreement between TST and QFT-GIT was 94%. Immigration employees had low return rates for their TST reading and second TST placement. Performing the one-visit QFT-GIT has administrative and logistical advantages in this occupational group. PMID- 22069931 TI - Worker-on-worker violence among hospital employees. AB - Violence toward hospital workers is an internationally recognized occupational hazard. While patients are frequently perpetrators of physical violence, other employees are often responsible for acts of nonphysical violence. However, few hospitals have systems for documenting and monitoring worker-on-worker violence. This study encompassed all incidents of worker-on-worker violence recorded by employees in a hospital system database over a six-year period. Incidence rates per 100 full-time equivalents (FTEs) and rate ratios (RR) were calculated by year, hospital, and job category. The majority (87%) of worker-on-worker incidents involved nonphysical conflict. The overall incidence rate was 1.65/100 FTEs, ranging among the six hospitals from 0.54 to 3.42/100 FTEs. Based on multivariate analysis, no single professional group was at increased risk for worker-on-worker violence. Co-worker violence threatens the well-being of hospital employees and should be regularly tracked with other forms of workplace violence so that suitable intervention programs can be implemented and assessed. PMID- 22069932 TI - Violence prevention in a small-scale psychiatric unit: program planning and evaluation. AB - Aggression against nurses and ancillary personnel is a major--overall under reported--occupational problem in sociomedical facilities for psychiatric and demented patients. The frequency of violent incidents against workers in a residential rehabilitation unit was assessed during medical examinations in the workplace between 1996 and 2009. The majority of the workers had been subjected to physical aggression over time. A violence prevention program that included educational, organizational, and medical measures was implemented in 2002. Interrupted time series analysis showed that the aggression trend prior to intervention was flat (beta3 = -0.004; SD = 0.003; P = 0.241), while there was a significant drop in aggressions after the intervention (beta3, = -0.149; SD = 0.018; P < 0.0001). No late increase in trend was observed in the post intervention period (beta3, = -0.006; SD = 0.004; P = 0.175). The program contributed to reducing violence in the workplace. PMID- 22069934 TI - Employability and HIV infection: can the military claim to be an exception? AB - To determine whether policies that exclude HIV-positive recruits from military service are scientifically and ethically justified, we reviewed the literature for evidence regarding their capacity to undertake rigorous exercise, the risks and benefits of exercise regimes, their risks from opportunistic infections and the extra burden of care, within military contexts. The literature suggests that HIV-infected persons with CD4 counts within the normal range have the exercise capacity and training benefits similar to uninfected persons. Subjects with modest CD4 depression are capable of moderate to strenuous exercise, without adverse consequences. Risks from opportunistic infections are mitigated with normal CD4 counts. Neurobehavioral impairment in asymptomatic HNV-positive patients is unlikely to reduce work capacity for most military occupations and can be easily identified by appropriate neurobehavioral testing. HIV testing alone is poorly predictive of competencies required for military employment. Testing should be used to promote access to care. Use for exclusionary purposes is discriminatory. PMID- 22069933 TI - A retrospective cohort study of lung cancer incidence in nylon flock workers, 1998-2008. AB - During an investigation of a novel interstitial lung disease in a cohort of nylon flock workers, a former worker was found to have developed bilateral synchronous pulmonary adenocarcinomas three decades after he quit smoking, suggesting that exposures in this industry might pose excessive risk of lung cancer. We conducted a retrospective cohort study of lung cancer incidence in the original study cohort (n=162) from August 15, 1998, to August 14, 2008. The Rhode Island Cancer Registry identified cohort members with lung cancer and provided age-gender-era specific rates of lung cancer in Rhode Island. Five cases of lung cancer occurred among cohort members versus 1.61 cases expected for a standardized incidence ratio of 3.1 (95% CI, 1.01-7.23). The observed threefold increase in lung cancer incidence could not be readily ascribed to chance, study bias, or uncontrolled confounding. Workers in this industry should be notified of their potentially increased risk of lung cancer. PMID- 22069936 TI - Great aesthetic expectations. PMID- 22069935 TI - Gets AIDS and survive? The "perverse" effects of aid: addressing the social and environmental determinants of health, promoting sustainable primary care, and rethinking global health aid. PMID- 22069937 TI - Like an axe, tools of the trade need sharpening. PMID- 22069938 TI - Management of fluorosis macro- and microabrasion. PMID- 22069939 TI - Dentistry is challenging: cosmetic dentistry even more! PMID- 22069940 TI - Composites in a three-dimensional world. PMID- 22069941 TI - Eight steps all dentists need to know about refining their scrap. PMID- 22069942 TI - Lithium disilicate: masking discolored teeth. PMID- 22069943 TI - Quick technique for evaluation of interocclusal space. PMID- 22069944 TI - Case of the elusive MB2 canal. PMID- 22069945 TI - Technique for the temporization of an anterior implant. PMID- 22069946 TI - The "first implant": protocol for the GP part 2, utilizing CT guides. PMID- 22069948 TI - Managing temporomandibular dysfunction requires accuracy. PMID- 22069947 TI - Dental cements: an overview. PMID- 22069949 TI - The diode laser--the diode laser for gingivectomies in orthodontics. PMID- 22069950 TI - Severe combined immunodeficiency (SCID): from molecular basis to clinical management. AB - Primary immune deficiency diseases (PID) comprise a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, as well as T and B lymphocytes. Severe combined immunodeficiency (SCID) is a group of disorders characterized by increased susceptibility to severe infections and early death. The diagnosis of SCID is supported by the demonstration of low absolute lymphocyte count and T cell lymphopenia (variably associated with numerical defects of B and NK cells). In the last two decades, advances in the characterization of the molecular pathophysiology of SCID, have permitted the development of novel diagnostic assays based on analysis of the expression of the disease-associated proteins and mutation analysis. More recently, pilot newborn screening programs for the identification of infants with SCID have been initiated in the United States. Prompt and aggressive treatment of infections, antimicrobial prophylaxis (in particular against Pneumocystis jiroveci) and regular administration of immunoglobulins are essential to reduce the risk of early death. However, survival ultimately depends on reconstitution of immune function, that is usually achieved by means of hematopoietic cell transplantation (HCT). Gene therapy and enzyme replacement therapy have also been used successfully is selected forms of SCID. Here we review the molecular and cellular pathophysiology and the mainstay of treatment of SCID. PMID- 22069951 TI - Prophylactic central neck dissection for papillary thyroid carcinoma: the terms of the debate. AB - An increasing interest in the management of central neck lymph nodes in the surgical treatment of papillary thyroid cancer is observed. While is widely accepted that patients with clinically apparent lymph nodes metastases should undergo compartment-oriented neck dissection, controversy exists about the need for prophylactic central neck dissection. The main issues that have been raised are the following ones: the definition of the anatomic boundaries and terminology of central neck dissection, the value of the recommendations expressed by the most authoritative association, the arguments in favour and against the appropriateness of prophylactic neck dissection, the laterality of central neck dissection. This article aims at reviewing the literature on prophylactic central neck dissection for papillary thyroid cancer in order to clarify some issues and to offer the reader a clear and concise overview of this complex debate. PMID- 22069952 TI - Care to relieve pain-stress in preterm newborns. AB - BACKGROUND AND AIM OF THE WORK: A variety of non-pharmacological pain-prevention and relief techniques have been studied to evaluate the pain reduction in neonates. The aim of our study was to compare the analgesic effect of sucking a pacifier with the use of eutectic mixture of local anaesthetics (EMLA) during venipuncture in preterm newborns, using physiological and behavioural parameters as indicators of pain. METHODS: We analysed the reaction to invasive procedures in 17 preterm newborns. Our patients underwent repeated vein draws without pain relief, sucking a pacifier, after the application of EMLA; we also evaluated a group of patients approached for care without pricking. For each infant we recorded the average values of the physiological parameters at rest and after pain stimuli, behavioural conditions (crying or grimaces), number and time required for blood draw. RESULTS: The maximum heart rate values, respiratory rate, and the maximum respiratory rate values presented a statistically difference only between subjects that underwent vein draws compared to subjects without pricking (p < 0.01). Moreover, the SpO2 parameter presented a significant increase in the control group compared to the others (p = 0.024). Analysis ofbehavioural parameters shows that crying seems significantly related to the duration and number ofvenipunctures (p = 0.000). CONCLUSIONS: It is clear that pain stress is more closely related to the duration and number of venipuncture than pain relief methods. Our results suggest that limiting the number and duration of vein draws could help to reduce pain stresss in preterm newborns. PMID- 22069953 TI - Certolizumab: efficacy and safety profile of a novel pegylated TNF-alpha blocking agent. AB - The treatment of Rheumatoid Arthritis (RA) has changed since the introduction of biological agents. In particular, the anti Tumor Necrosis Factor (TNF)-alpha molecules have been the first group of drugs showing a good efficacy and safety profile. Among these, a new anti TNF-alpha antibody has been recently indicated for the treatment of RA: certolizumab pegol (CZP). In the main clinical trials this new pegylated anti TNF-alpha has shown to be efficacious on clinical, functional and prevention of structural damage in patients with active RA and with inadequate response to traditional disease modifying drugs, including methotrexate. Moreover CZP showed to be well tolerated and most adverse events occurred were mild or moderate. Therefore, results obtained showed that this new molecule can play a role in the treatment of RA. PMID- 22069954 TI - Clinical effectiveness of a highly standardized and bioavailable mixture of flavonoids and triterpenes in the management of acute hemorroidal crisis. AB - BACKGROUND AND AIM OF THE WORK: Patients with acute haemorrhoidal crisis often need of an immediate and effective pharmacological approach to alleviate their pain, bleeding and swelling or have to be referred by the general practitioner to the surgeon for a definitive treatment. Effective and not invasive treatment control of the acute crisis could be of practical use in order to avoid or to delay invasive procedures to a time more convenient for the patient and/or for the surgeon. METHODS: After enrolling, according to the group treatment, every patient starts taking 1 tablet every 8 hours for 7 days of Emospid or 2 tablets every 8 hours for 7 days of MMDH tablets. According to a simplified PATE 2000 classification, the following parameters were evaluated: haemorrhoidal grade, internal and external haemorrhoids, internal and external oedema, internal and external thrombosis, bleeding, bleeding intensity, pain, itching, defecation problems and urgency, tenesm, mucus in stools and sphinterial tone. RESULTS: In the Emospid group, within the considered period, 35 patients out 40 shift downwards of 1 grade of the haemorrhoidal scale (from III to II and from II to I); 22 out of 29 stop bleeding; bleeding intensity drops by about 90%; pain ceased in 33 out of38; pain intensity drops by about 75%; itching ceased in 25 out 35; tenesm ceased in 32 out of 33; sphinterial tone reduced from hypertonic to normal in 19 out 24; mucus in the stools was found in 3 out of 12; 12 out 35 still presented defecation disorders; defecation urgency was found in 2 out of 14; need to defecate in 2 times was found in 1 out of 17; acute events (external and/or internal oedema, external and/or internal thrombosis) was found in 10 out of 36. In the MDHH group results were, in terms of global evaluation, inferior of about 25-50% according to the considered parameter when compared with the one got by the Emospid treatment. CONCLUSIONS: Patients with acute haemorrhoidal crisis may be successfully treated with Emospid in order to avoid or to delay, if acute crisis relapsed, invasive procedures. Moreover, the treatment with Emospid shows to be more effective, if compared with MMDH, in counteracting acute haemorrhoidal crisis. (www.actabiomedica.it) PMID- 22069955 TI - Visceral ischaemia and organ dysfunction after hybrid repair of complex thoraco abdominal aneurysms. AB - BACKGROUND: The visceral hybrid repair of thoracoabdominal aneurysms (TAAAs) is a feasible and relatively safe alternative to traditional open repair in a cohort of patients at high surgical risk, averting the need for thoracotomy and supra coeliac aortic cross clamping. The visceral ischaemia-reperfusion syndrome and organ dysfunction following visceral debranching is still unkown. This study investigates the relationship between visceral ischemia and multi system organ dysfunction. PATIENTS AND METHODS: 18 consecutive patients undergoing elective, urgent and emergent hybrid repair of TAAAs between February 2005 and October 2007 were prospectively analyzed. Preoperative organ dysfunction and intraoperative risk factors (operating time, extent of the aneurysm, number of visceral vessels by passed) were assessed and compared with postoperative organ dysfunction (pulmonary, hepatic, renal, pancreatic and haematological disorders). Blood sampling for neutrophil CD 11b quantification was performed at baseline, on postoperative days 1, 3, 7 and before discharge. RESULTS: Perioperative Multi System Organ Dysfunction (MSOD) was diagnosed in 22.2% of patients (n = 4/18). Three of these patients died within 30 days (16.7%, n = 3/18). No relationship between preoperative organ dysfunction, blood loss, or operative time and postoperative organ dysfunction was observed. A significant correlation between the visceral retrograde revascularization and postoperative neutrophil expression in MSOD patients regardless of preoperative neutrophil baseline, TAAA extent and number of vessels by passed was present. CONCLUSIONS: Upregulation of neutrophils may be responsible for the higher incidence of MSOD and it may be an important marker predicting a severe multiple organ failure following visceral debranching in hybrid procedures. PMID- 22069956 TI - Lichen sclerosus: a review of literature and a case of an atypic surgical treatment. AB - Lichen sclerosus is a chronic immuno-mediated skin disease of the genital region in men and women. The treatment may be pharmacological or surgical, the choice depending on the extension of the involved area, the histological pattern and the level of functional disease complained by the patient. If the biopsy is negative for neoplastic degeneration the treatment may be pharmacological only. In our paper, we describe the case of a patient with vulvar disease and labial fusion, burial of the clitoris and severe introital stenosis. In this case, the treatment was surgical. PMID- 22069957 TI - Chronic thromboembolic pulmonary hypertension: take care to a "favourable" apparently evolution. A case report. AB - Chronic thromboembolic pulmonary hypertension (CTEPH) caused by intraluminal thrombus organization and fibrous stenosis or complete obliteration of pulmonary arteries, is a not rare but life-threatening complication of acute pulmonary embolism. The prognosis of medically treated patients with CTEPH is poor and worsens as pulmonary hypertension exacerbates. We describe the case of a 43-years old with a history of progressive shortness of breath, hemoptysis, chest discomfort and syncope. Echocardiographic and imaging studies showed changes consistent with chronic thromboembolic pulmonary hypertension. Further work-up showed only moderate increase of homocysteine level with negative features for lupus and others primary thrombophilic disease. The patient was managed adequately with thrombolytic and inotropic therapy; oral anticoagulation was started with improvement of his clinical status and was screened for pulmonary thrombo endarterectomy, but he refused. The case presented despite its evolution 'temporarily' positive perhaps related to the reduction of hemodynamic overload through bronchial arteries, reiterates the importance of early surgical intervention, before it establishes the hypertensive vasculopathy. Abnormal pulmonary function at rest and after exercise stress test associated to non invasive echocardiographic measurements are an excellent tool to identify the bad prognosis patients in CTEPH. We discuss the pathophysiology and conclude that in selected cases, pulmonary thromboendarterectomy is the best therapy, but only if executed early. PMID- 22069958 TI - Use of a diode laser in an excisional biopsy of two spoonlike neoformations on the tongue tip. AB - The 810 nm diode laser, due to its high affinity with haemoglobin (elective chromatophore) revealed, by itself, as elective instrument for surgical excision of the tongue, an organ highly vascularized and sensitive to the laser cutting action. The advantages for its use, with respect to the traditional cold blade surgery, are its haemostatic effect (which avoids to close wounds by stitches) and, not less important, the decontaminant effect of the laser ray, due to either the thermal raising created on cutting line and/or the specific selective action exerted on the bacterial membrane by its wavelength. Finally, the analgesic effect of the diode laser contributes to consider this kind of procedure more comfortable for the patient who often roundly requires its use. PMID- 22069959 TI - Desmoplastic fibroma of the mandible. AB - We report the imaging findings of a desmoplastic fibroma (DF) of the mandible in a 3 years old girl. DF of bone is a rare, no-metastasizing but locally aggressive tumor. Hypercellularity, nuclear pleomorphism, mitotic activity, and traces of odontogenic epithelium and bony tissue are absent. US exam showed a highly vascular and well delimited mass, with no necrotic/hemorrhagic areas. It appeared as a well-defined osteolytic region in RX and a multiloculated, hypodense mass, with no periosteal reaction signs, in CT scans. MRI showed hypointensity in T1w TSE sequence and hyperintensity both in T1w TSE SPIR and T2w ones with no restriction of the "apparent diffusion coefficient" (ADC). In conclusion, remaining histology the gold standard for the DF diagnosis, imaging features may strongly suggest it. PMID- 22069960 TI - A rare location of Crohn's disease: the nasal mucosa. AB - Crohn's disease (CD) is a chronic inflammatory disease that affects both the small and large intestine in approximately 40% of cases, solely the ileum or the colon in 30% and 25%, respectively. The remaining locations of the gastrointestinal (GI) tract are involved in percentages ranging between 0.5 and 5%. The appearance of the disease outside the GI tract is an exceptional event. In the present case, the authors report the history of a male patient suffering from CD involvement of almost the entire digestive system plus the nasal mucosa. This latter event emerged after repeated episodes of epistaxis, the demonstrations of histologic nasal features similar to those of intestinal CD, and the remission after treatment with beclomethasone. Since in literature less than a decade of cases of nasal location of CD was described, it is of prime importance to highlight that in CD patients, the occurrence of repeated episodes of epistaxis should prompt a consideration in the differential diagnosis of nasal location of the disease. PMID- 22069961 TI - Report of two cases of Castleman's Disease: a case of benign localized disease and a case of fast progressive multicentric disease. AB - Castleman's Disease is a rare tumour involving lymph node tissues; a case of benign localized disease and a case of rapid progressive multicentric disease are reported. Case report 1: A 19-year-old man presented with four months of hypogastric and left iliac pain. Castleman's Disease was suspected after CT-scan. A CT-guided fine-needle biopsy of the lesion was performed revealing hyaline vascular type Castleman's Disease. The patient underwent open surgery with radical excision of the lesion. No adjuvant therapy was performed after surgery. The patient is alive and disease-free after 24 months. Case report 2: A 58-year old woman presented with a right axillary palpable lymph node and vague abdominal discomfort. Abdomen CT demonstrated hepatosplenomegaly associated with adenopathy at the hepatic hilus and splenic hilus; dilatation of intra-hepatic biliary ducts was present. The axillary node was excised, the mass at hepatic hilus was biopsied. The diagnosis was Castleman's Disease in both sites. In course of steroid therapy retroperitoneal multiple nodes appeared associated with fast progressive mechanic jaundice and liver failure. Progressive multi-organ failure arose within 1 week, with irreversible clinical worsening to death. PMID- 22069962 TI - Hepatoprotective activity of a phytotherapeutic formula on thioacetamide--induced liver fibrosis model. AB - Hepatic fibrosis is a widespread alteration in the liver that primarily consists of increased collagen deposition in the tissue. The aim of the present study was to evaluate the protective effects of poly-phytocompound EH-1501 containing small amounts of silymarin but also other potentially effective substances on thioacetamide (TTA)-induced liver fibrosis and to elucidate the mechanisms underlying these protective effects in rats. Forty rats were randomly divided into four groups. Liver fibrosis was induced by intraperitoneal injection of 200 mg/kg body weight. TAA dissolved in saline was administered thrice a week, for 8 weeks. Groups 1 (normal healthy control) and 2 (liver injury model) received water for 8 weeks or silymarin (50 mg/kg p.o. daily) for 8 weeks (group 3) or a poly-phytocompound EH-1501 (containing grape leaf, wild strawberry, dandelion and milk thistle, EuroHealth, Italy) (200 mg/kg, daily respectively) for 8 weeks (group 4). Biochemistry and serum fibrosis markers were AST, ALT, GGT, bilirubin, thiobarbituric acid reactive substances (TBARs), hyaluronic acid and type IV collagen 7s. Liver tissue was used to assay glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), TBARs, hydroxyproline and gene expression of collagen alpha1 (col alpha1) and transforming growth factor-beta1 (TGF-beta1). Silymarine and EH-1501 were equally effective in reducing serum markers of liver damage and fibrosis as well as oxidative stress. However, as compared to silymarine, EH-1501 was significantly more effective in improving tissue level of GPx while decreasing TBARs and hydroproline content (p < 0.05). When looking at gene expression of col alpha1 and TGF-beta1, EH-1501 showed a significantly higher degree of gene down-regulation as compared to silymarine (p < 0.05). Taken altogether, these data suggest that a natural antioxidant containing phytocompound EH-1501 exerts an effective hepatoprotective property in experimental chronic fibrotizing liver injury to a significantly higher degree than silymarin. PMID- 22069963 TI - [Preliminary clinical results of endoscopic discectomy followed by interbody fusion using B-Twin expandable spinal spacer]. AB - OBJECTIVE: To investigate the effectiveness and significance of percutaneous endoscopic discectomy followed by interbody fusion using B-Twin expandable spinal spacer for degenerative lumbosacral disc METHODS: Between January 2007 and August 2008, 21 patients with degenerative lumbosacral disc disease were treated with endoscopic discectomy followed by interbody fusion using B-Twin expandable spinal spacer. Among them, there were 13 males and 8 females with an average age of 52 years (range, 28-79 years). And the disease duration ranged from 3 months to 40 years (median, 9 months). The affected segments included T11, 12, T12-L1, L1.2, and L2, 3 in 1 case respectively, L4, 5 in 4 cases, and L5, S1 in 13 cases. All patients had intractable low back pain or lower extremity radicular symptoms. The placement methods of B-Twin expandable spinal spacer were double sides in 15 cases and single side in 6 cases. Oswestry Disability Index (ODI) and Macnab grading were used to determine the function recovery after operation. And Suk's standard was used to determine the fusion effects by X-ray. RESULTS: All 21 patients were followed up 18 months to 3 years (mean, 23.8 months). Sciatica symptoms disappeared after operation in 19 cases, no significant improvement occurred in 2 cases of thoracic disease. The ODI scores were 79% +/- 16% at preoperation, 30% +/- 9% at 1 month, 26% +/- 10% at 3 months, 21% +/- 12% at 6 months, and 20% +/- 10% at 18 months after operation, showing significant differences between pre- and postoperation (P < 0.05). According to Macnab grading at 6 months postoperatively, the results were excellent in 14 cases, good in 5 cases, and fair in 2 cases with an excellent and good rate of 90.5%. According to Suk et al. standard, the results were excellent in 1 case, good in 19 cases, and poor in 1 case with an excellent and good rate of 95.2%. The muscle strength of the lower extremities had no improvement in 1 case of T11, 12 disc protrusion; pedicle screws fixation and decompression laminectomy were given after 6 months, but no improvement was achieved during follow-up. Protrusion recurred after 4 months in 1 case of L4, 5 disc protrusion, then was cured by laminectomy discectomy. The remaining patients achieved postoperative relief. CONCLUSION: Endoscope combined with interbody fusion is a good combination to solve lumbar instability. B-Twin expandable spinal spacer is a minimally invasive fusion choice of 4, 5 and L5, S1. PMID- 22069964 TI - [Microendoscopic decompression via unilateral approach for lumbar spinal stenosis]. AB - OBJECTIVE: To investigate the effectiveness and safety of microendoscopic decompression via unilateral approach for lumbar spinal stenosis. METHODS: Between May 2006 and June 2009, 79 patients with lumbar stenosis were treated and divided into 2 groups: posterior lamina fenestration decompression (group A, n = 37), endoscopic decompression via unilateral approach (group B, n = 42). There was no significant difference in age, sex, segment level, and disease duration between 2 groups (P > 0.05). The clinical outcomes were assessed by using the visual analogue scale (VAS) score and Oswestry Disability Index (ODI). The operation time, blood loss, complications were compared between 2 groups. RESULTS: Operations were successfully performed in all cases. The operation time, blood loss, and drainage volume were (75.0 +/- 25.7) minutes, (140.3 +/- 54.8) mL, and (46.5 +/- 19.7) mL in group A, were (50.4 +/- 18.2) minutes, (80.2 +/- 35.7) mL, and (12.7 +/- 5.3) mL in group B; there were significant differences between 2 groups (P < 0.05). All the wounds healed by first intention. All patients were followed up 12-39 months (mean, 16 months). In group A, 1 patient suffered from intervertebral space infection after operation and recovered after conservative treatment; 4 patients had lumbar instability after operation and recovered after lumbar interbody fusion combined with spine system internal fixation. In group B, 2 patients suffered from spinal dural rupture during operation and recovered after corresponding treatment, and no lumbar instability was found. There was no significant difference in VAS score and ODI between 2 groups at preoperation (P > 0.05). Both VAS score and ODI were significantly improved at early stage after operation and last follow-up when compared with preoperation in each group (P < 0.05). Comparing with group A, there was significant improvement in VAS score at 24 hours postoperatively and in ODI at 1 month postoperatively in group B (P < 0.05), but no significant difference was observed at last follow-up (P > 0.05). According to clinical evaluation of ODI improvement rate, the excellent and good rate was 89.2% in group A and 92.9% in group B, showing no significant difference (chi2 = 0.896, P = 0.827). CONCLUSION: Comparing with posterior decompression surgery, microendoscopic decompression via unilateral approach is one of effective method to treat lumbar stenosis, with less trauma of fenestration yield and good early outcomes. PMID- 22069965 TI - [Analysis of effectiveness of interrupt percutaneous endoscopic lumbar discectomy through interlaminar approach for L5, S1 disc protrusion]. AB - OBJECTIVE: To evaluate the effectiveness of interrupt percutaneous endoscopy lumbar discectomy (PELD) through interlaminar approach for L5, S1 disc protrusion. METHODS: Between November 2006 and August 2010, 115 patients with L5, S1 disc protrusion were treated, including 79 males and 36 females with an average age of 38 years (range, 14-79 years). All patients showed the dominated symptom of the S1 nerve root. The working channel was established by puncturing through interlaminar approach under the local anesthesia. After the needle was used to make sure no nerve root or dural sac on working face, the disc tissue was excised directly by blind sight. Then the nerve root decompression was observed through the endoscope. In patients with free type, fragment compression was observed through the endoscope, and the disc tissue around the nerve roots was removed, then the free disc tissue around intervertebral space was excised. RESULTS: One patient who failed to puncture changed to miniopen discectomy; 3 patients who failed changed to post lateral approach; and the others underwent interrupt PELD through interlaminar approach. Eighty patients were followed up 18 months on average (range, 12-36 months). The average Oswestry Disability Index (ODI) was reduced to 13% +/- 5% at 12 months after operation and to 12% +/- 8% at last follow-up from 73% +/- 12% at preoperation, showing significant differences (P < 0.01). According to modified Macnab's criterion, the results were excellent in 59 cases, good in 15 cases, fair in 3 cases, and poor in 3 cases at last follow-up, and the excellent and good rate was 92.5%. CONCLUSION: For the treatment of disc protrusion at the L5, S1 level, interrupt PELD through interlaminar approach should be ideal with short operation time, small trauma, and quick recovery. PMID- 22069966 TI - [Clinical observation of anterior bone graft fusion and internal fixation to treat adjacent multivertebral tuberculosis in one-stage]. AB - OBJECTIVE: To evaluate the method and effectiveness of anterior focus clearance with autograft bone fusion and internal fixation in treating of adjacent multivertebral tuberculosis in one-stage. METHODS: Between March 2007 and September 2009, 8 cases of thoracic vertebra tuberculosis were treated. Of 8 cases, 6 were male and 2 were female, aged 32 years on average (range, 20-42 years). The disease duration ranged from 8 to 14 months (mean, 10.2 months). Affected vertebrae included thoracic vertebrae in 35 cases and lumbar vertebrae in 11 cases; 5 vertebrae were involved in 4 cases, 6 vertebrae in 3 cases, and 8 vertebrae in 1 case. According to Frankel classification, there were 2 cases of grade C, 4 cases of grade D, and 2 cases of grade E. All patients had different kyphosis with the Cobb angle of (25.1 +/- 6.6) degrees. All patients received antituberculous therapy 4-6 weeks preoperatively; after complete clearance lesions, autograft bone fusion and internal fixation were performed, and then antituberculous therapy was given for 18 months. RESULTS: All incisions healed by first intention. Eight patients were followed up 18-48 months (mean, 29 months). According to JIN Dadi et al. criterion, 7 cases recovered after first operation, 1 case of relapsed tuberculosis with sious was cured after re-focus clearance. The Cobb angle was (19.5 +/- 4.2) degrees at 7 days after operation and was (22.3 +/- 3.6) degrees at last follow-up, showing significant differences when compared with the preoperative value (P < 0.05). The nerve function of all cases were classified as Frankel grade E. CT scan showed bone graft fusion at 6-8 months after operation. No loosening or displacement of grafted bone and internal fixation occurred during follow-up. CONCLUSION: The treatment of adjacent multivertebral tuberculosis by anterior focus clearance, intervertebral autograft, and internal fixation in one-stage is effective. Anterior bone fusion and internal fixation in one-stage can correct kyphosis effectively and rebuild spinal stability, so it is a good choice for surgical treatment of adjacent multivertebral tuberculosis. PMID- 22069967 TI - [One-stage posterior debridement, bone graft, and internal fixation for thoracic tuberculosis]. AB - OBJECTIVE: To evaluate the clinical effectiveness and advantages of one-stage posterior debridement, bone graft, and internal fixation for thoracic tuberculosis. METHODS: The data were retrospectively analysed, from 21 cases of thoracic tuberculosis undergoing one-stage posterior debridement, bone graft, and internal fixation between June 2007 and November 2009. There were 16 males and 5 females with an average age of 42.2 years (range, 22-73 years). The average disease duration was 13.2 months (range, 7-21 months). The lesions were located at the level of T5,6 (1 case), T6,7 (1 case), T8,9 (4 cases), T9,10 (3 cases), T10,11 (5 cases), T11,12 (6 cases), and T9-11 (1 case). According to the Frankel grading criterion, the neurological function was rated as grade B in 2 cases, grade C in 6 cases, grade D in 10 cases, and grade E in 3 cases. The preoperative Cobb angle was (26.3 +/- 9.2) degrees. The erythrocyte sedimentation rate (ESR) was (35.9 +/- 11.2) mm/1 hour. RESULTS: Thoracic tuberculosis was confirmed in postoperative pathological examination in all 21 cases. All incisions healed primarily without fistulae formation. The average follow-up time for 21 patients was 16.2 months (range, 1-3 years). Bony fusion was achieved within 7-12 months (mean, 9 months) without pseudoarthrosis. No loosening and breakage of internal fixation were found, and no local recurrence occurred. The ESR decreased to (25.1 +/- 8.9) mm/1 hour at 1 week postoperatively, showing significant difference when compared with preoperative value (t = 5.935, P < 0.01); it decreased to (14.1 +/- 4.6) mm/1 hour at 3 months postoperatively. According to Frankel grade, the neurological function was significantly improved at 1 year after operation (chi2 = 13.689, P = 0.003). The average Cobb angle was (17.1 +/- 4.5) degrees at 1 years postoperatively, showing significant difference when compared with preoperative value (t = 7.476, P < 0.01). CONCLUSION: One-stage posterior debridement, bone graft, and internal fixation has a good clinical effectiveness for thoracic tuberculosis with less injury and complete focal cleaning, as well as a good effectiveness of spinal canal decompression and kyphosis deformity correction. PMID- 22069968 TI - [Debridement and allograft with internal fixation via combined anterior and posterior approach for treatment of lumbosacral tuberculosis]. AB - OBJECTIVE: To investigate the effectiveness of radical debridement, reconstruction with bone allograft, and pedicle screw-rod internal fixation via combined anterior and posterior approach in the treatment of lumbosacral tuberculosis. METHODS: Between January 2005 and May 2010, 16 patients with lumbosacral tuberculosis were treated. Radical debridement was performed via extraperitoneal approach, then tricortical iliac bone allograft was placed and pedicle screw-rod internal fixation was used to reconstruct the spinal column. There were 12 males and 4 females aged 38-65 years (mean, 48 years). The disease duration ranged from 6 to 24 months (mean, 10 months). The main clinical symptom was persistent pain in lumbosacral area. The involved segments included L4,5 (3 cases), L5, S1 (8 cases), and l-S1 (5 cases). The lumbosacral angle was 18-32 degrees (mean, 22 degrees). The erythrocyte sedimentation rate (ESR) was 15-55 mm/1 hour (mean, 25 mm/1 hour). All the patients were given antituberculosis chemotherapy for 12 months after operation. RESULTS: The operation time was 120 240 minutes (mean, 180 minutes). The amount of bleeding was 300-600 mL (mean, 420 mL). All wounds healed by first intention, and no relative complication occurred. All 16 cases were followed up 12-24 months (mean, 16 months). No recurrence occurred and ESR recovered to normal. Persistent pain in lumbosacral area and radicular pain in lower extremities disappeared. The X-ray films demonstrated that bony fusion was obtained in all patients at 8-12 months postoperatively. The lumbosacral angle was 16-31 degrees (mean, 21 degrees) at last follow-up. CONCLUSION: The extraperitoneal approach can provide direct and safe access to the lesion. The structural iliac bone allograft and posterior instrumentation could reconstruct effectively the stability of the lumbosacral junction. PMID- 22069969 TI - [Correlative factors of secondary fracture after percutaneous kyphoplasty for osteoporotic vertebral compression fracture]. AB - OBJECTIVE: To analyse the correlative factors of secondary vertebral fracture after percutaneous kyphoplasty (PKP) in treatment of osteoporotic vertebral compression fracture (OVCF) at different levels (adjacent and/or nonadjacent levels). METHODS: Between December 2002 and May 2008, 84 patients with OVCF were treated with PKP, and the clinical data were analysed retrospectively. There were 11 males and 73 females with an average age of 70.1 years (range, 55-90 years). All patients were followed up 24-96 months (mean, 38 months). Secondary vertebral fracture occurred in 12 cases at 3-52 months after PKP (secondary fracture group), no secondary fracture in 72 cases (control group) at over 24 months. The preoperative bone mineral density, postoperative vertebral height compression rate, postoperative Cobb angle, amount of injected bone cement per vertebra, puncture pathway (uni- or bilateral puncture), age, gender, number of fracture segment, and cement intradiscal leakage were compared between 2 groups to find correlative factors of secondary vertebral fractures. RESULTS: There was no significant difference in preoperative bone mineral density, postoperative vertebral height compression rate, postoperative Cobb angle, amount of injected bone cement per vertebra, puncture pathway, age, gender, and number of fracture segment between 2 groups (P > 0.05). But the incidence of cement intradiscal leakage was much higher in secondary fracture group than in control group (chi2 = 5.294, P = 0.032). CONCLUSION: Cement intradiscal leakage may be the correlative factor of secondary vertebral fracture after PKP in OVCF. PMID- 22069970 TI - [Treatment of type IV Pipkin fracture through transtrochanteric approach with trochanteric osteotomy]. AB - OBJECTIVE: To summarize the short-term effectiveness of type IV Pipkin fracture through transtrochanteric approach with trochanteric osteotomy. METHODS: Between January 2007 and January 2010, 15 cases of type IV Pipkin fracture were treated through transtrochanteric approach with trochanteric osteotomy. There were 9 males and 6 females with an average age of 42.5 years (range, 27-55 years). The causes of fractures included traffic accident (12 cases), falling from height (2 cases), and heavy pound injury (1 case). The time from injury to hospitalization was 4 hours to 7 days (mean, 2.3 days). All patients had limitation of activity in the injured hips. The X-ray films and CT three-dimensional reconstruction indicated posterior dislocation of the hip joints and fractures of the femoral head and acetabulum, with no fracture of femoral neck. The locations of the femoral head fractures were under the round ligament in 9 cases and above the round ligament in 6 cases. Complications were treated firstly in all patients. The time from hospitalization to operation ranged from 2 to 10 days (mean, 4.5 days). RESULTS: All patients got primary wound healing with no early complication. All the patients were followed up 12-48 months with an average of 26 months. All osteotomies and acetabular fractures healed within 6 to 8 weeks. All patients achieved healing of femoral head fracture after 6-10 months. Mild heterotopic ossification occurred in 2 cases at 3 months after operation which were left untreated; and necrosis of the femoral head occurred in 1 case at 8 months after operation, was treated by total hip arthroplasty. At last follow-up, the flexion of the injuried hips ranged from 60 to 120 degrees (mean, 92.5 degrees). Based on Thompson et al. scoring scales, the results were excellent in 5 cases, good in 7 cases, fair in 2 cases, and poor in 1 case; the excellent and good rate was 80%. CONCLUSION: Treatment of type IV Pipkin fracture through transtrochanteric approach with trochanteric osteotomy can provide good visualization and protection of the blood supply of the femoral head. PMID- 22069971 TI - [Femoral reconstruction in patients with proximal femoral deformity in total hip arthroplasty]. AB - OBJECTIVE: To evaluate the clinical results of the femoral reconstruction technique in patients with proximal femoral deformity in total hip arthroplasty. METHODS: Between March 2004 and June 2009, total hip arthroplasty procedures were performed on 25 patients (26 hips) with hip joint disease and proximal femoral deformity, including primary osteoarthritis of the hip joint (2 hips), developmental dysplasia of the hip (8 hips), traumatic arthritis of the hip (14 hips), and tuberculosus arthritis of the hip (2 hips). There were 10 males (10 hips) and 15 females (16 hips), with an average age of 64 years (range, 42-82 years). The disease duration was 10 months to 25 years (mean, 10.6 years). The Harris score was 44.2 +/- 5.1, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 45.0 +/- 2.7 before operation. According to Berry's classification system of primary disease, 8 hips were classified as developmental dysplasia of hip, 7 hips as malunion of fracture, 2 hips as chronic tuberculosis, 2 hips as slipped femoral epiphysis, 1 hip as previous subtrochanteric osteotomy, 1 hip as previous shelf operation of the acetabulum, and 5 hips as previous internal fixation; according to the anatomic site of the deformity, there were 5 hips of greater trochanter, 10 hips of femoral neck level, 10 hips of metaphyseal level, and 1 hip of diaphysis. RESULTS: All wounds healed by first intention. Deep venous thrombosis occurred in 3 patients within 1 week, and were cured with braking and anticoagulant therapy. Bursal synovitis of great trochanter occurred in 1 patient after 6 weeks, and was eased after taking drugs for pain relief. All patients were followed up 1 year and 6 months to 6 years, with an average of 3 years and 3 months. The Harris score and WOMAC score at last follow-up were 88.4 +/- 3.6 and 82.0 +/- 5.2 respectively, showing significant differences when compared with preoperative scores (P < 0.05). The X ray films at last follow-up showed good location of prosthesis and no loosening expect 1 patient who had aseptic loosening and was given revision at 8 months postoperatively. CONCLUSION: Proximal femoral deformity classification will contribute to the choice of prosthesis and surgical strategy, thus the good results of femoral reconstruction and clinical results would be obtained. PMID- 22069972 TI - [Therapeutic effectiveness of intra-knee-articular injection of platelet-rich plasma on knee articular cartilage degeneration]. AB - OBJECTIVE: Platelet-rich plasma (PRP) can enhance the chondrocyte proliferation and repair of cartilage defects. To explore the safety and efficacy of intra-knee articular injection of PRP to treat knee articular cartilage degeneration by comparing with injecting sodium hyaluronate (SH). METHODS: Thirty consecutive patients (30 knees) with knee articular cartilage degeneration were selected between January 2010 and June 2010. According to different injections, 30 patients were randomly divided into PRP group (test group, n = 15) and SH group (control group, n = 15). There was no significant difference in gender, age, body mass index, and Kellgren-Lawrence grade between 2 groups (P > 0.05). Test group received 3.5 mL of PRP intra-knee-articular injections while control group received 2 mL of SH during the same time period. Both treatments were administered in series of 3 intra-knee-articular injections at 3-week intervals. Then, adverse reactions were recorded. International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Lequesne index were used for evaluation of treatment results. RESULTS: The patients of 2 groups were followed up 6 months. There were significant differences in IKDC score, WOMAC score, and Lequesne index between pre- and post-injection in 2 groups (P < 0.05); no significant difference was found between different time points (3, 4, and 6 months) in test group (P > 0.05), while significant differences were found between the postoperative 6th month and the postoperative 3rd and 4th months in control group (P < 0.05). There was no significant difference in IKDC score, WOMAC score, and Lequesne index between 2 groups within 4 months (P > 0.05), but the effectiveness of test group was significantly better than that of control group at 6 months after injection (P < 0.05). Adverse reactions occurred in 12 patients (31 injections) of test group and in 12 patients (30 injections) of control group. No significant difference in onset time, termination time, and duration of adverse reactions were found between 2 groups (P > 0.05). CONCLUSION: Intra-knee-articular injection of PRP to treat knee articular cartilage degeneration is safe, which can alleviate symptoms of pain and swelling and improve the quality of life of patients; however, further data of large samples and long-term follow-up are needed to confirm the safety and effectiveness. PMID- 22069973 TI - [Multi-spot suture fixation under arthroscope for treating tibial intercondylar anterior eminence fracture]. AB - OBJECTIVE: To explore the surgical method and effectiveness of multi-spot suture fixation under arthroscope in treating tibial intercondylar anterior eminence fracture. METHODS: Between February 2006 and January 2010, 15 patients with tibial intercondylar anterior eminence fracture were treated with multi-spot suture fixation under arthroscope after fracture reduction. There were 14 males and 1 female with a median age of 33 years (range, 7-55 years). The injury causes were traffic accident in 9 cases, sport in 2 cases, and falling in 4 cases. The anterior drawer test, Lachman test, and pivot shift test in all the cases turned out to be positive. The Lysholm score was 64.7 +/- 1.3. According to Meyers McKeever classification, 5 cases were classified as type II, 7 cases as type III, and 3 cases as type IV. Of them, 13 cases had fresh fracture and 2 cases had old fracture. Assisted with anterior cruciate ligament-aimer, bone tunnels (2 mm in diameter) were built through the fracture fragments after fracture reduction, through which Ethibond 2 polyester sutures were guided into the joint by No.18 spine needles; after knot of 2 sutures or knot of only 1 suture was made, the other ends of sutures were fastened together outside the joint. RESULTS: The incisions of all the cases healed by first intention with no complication of infection or deep venous thrombosis. Fifteen patients were followed up 14-48 months with an average of 24.2 months. The X-ray examination indicated fractures healed in all the cases at 2-4 months (mean, 3 months). At 6 months after operation, 14 cases showed negative results of Lachman test and anterior drawer test but 1 case positive, while all the cases showed negative results in pivot shift test. The extension and flexion spheres of knee activity were normal in 13 cases and were limited in 2 cases. The Lysholm score was 95.1 +/- 2.1, showing significant difference when compared with the preoperative score (t = 43.020, P = 0.000). CONCLUSION: Multi-spot suture fixation under arthroscope is an effective method with small invasion, reliable fixation, and simple operation for treating tibial intercondylar anterior eminence fracture. PMID- 22069974 TI - [Comparison study on effectiveness between arthroscopy assisted percutaneous internal fixation and open reduction and internal fixation for Schatzker types II and III tibial plateau fractures]. AB - OBJECTIVE: To compare the effectiveness of arthroscopy assisted percutaneous internal fixation and open reduction and internal fixation for Schatzker types II and III tibial plateau fractures. METHODS: Between August 2006 and April 2010, 58 patients with tibial plateau fractures of Schatzker types II and III were treated with arthroscopy assisted percutaneous internal fixation (arthroscopy group, n = 38), and with open reduction and internal fixation (control group, n = 20). There was no significant difference in gender, age, disease duration, fracture type, and complication between 2 groups (P > 0.05). The operation time, incision length, fracture healing time, and complications were compared between 2 groups. Knee function score and the range of motion were measured according to American Hospital for Special Surgery (HSS) score standard. RESULTS: All patients achieved primary incision healing. The arthroscopy group had smaller incision length and longer operation time than the control group, showing significant differences (P < 0.05). The patients of 2 groups were followed up 12 to 14 months. At 6 months, the HSS score and the range of motion of the arthroscopy group were significantly greater than those of the control group (P < 0.05). The X-ray films showed bony union in 2 groups. The fracture healing time of the arthroscopy group was shorter than that of the control group, but no significant difference was found (t = 2.14, P = 0.41). Morning stiffness occurred in 2 cases (5.3%) of the arthroscopy group, joint pain in 6 cases (30.0%) of the control group (3 cases had joint stiffness) at 1 week, which were cured after symptomatic treatment. There was significant difference in the incidence of complications between 2 groups (chi2 = 6.743, P = 0.016). CONCLUSION: The arthroscopy assisted percutaneous internal fixation is better than open reduction and internal fixation in the treatment of tibial plateau fractures of Schatzker types II and III, because it has smaller incision length and shorter fracture healing time. PMID- 22069976 TI - [Effectiveness of microsurgical repair of flexor tendon rupture by non-knot Kessler suture method in anastomotic stoma]. AB - OBJECTIVE: To analyze the effectiveness and advantages of the microsurgical repair of flexor tendon rupture with non-knot Kessler suture method in anastomotic stoma by comparing with the method of traditional Kessler suture. METHODS; Between February 2005 and February 2010, 122 patients (163 fingers with 243 flexor digital tendons) with flexor tendon rupture, were treated with microsurgical repair by non-knot Kessler suture method (treatment group); flexor tendon was sutured, and sodium hyaluronate was used to repair tendon membrane, tendon sheaths, and the tissue surrounding tendons. The clinical data were analysed, and were compared with ones from 96 patients (130 fingers with 186 flexor digital tendons) with flexor tendon rupture treated with traditional Kessler suture between February 2001 and February 2005 (control group). There was no significant difference in gender, age, cause of injury, injury site, duration, and other general information between 2 groups (P > 0.05). Kleinert elastic traction therapy (dynamic-protection) was performed at 3 weeks after surgery, and the finger function exercise was done after 24 hours. RESULTS: Infection of incision occurred in 2 cases of the treatment group and in 5 cases of the control group, and were cured after 2 weeks of dressing change; the other incisions healed by first intention. The patients were followed up 6 to 14 months (mean, 9 months). In the treatment group, the total active movement (TAM) was (192.0 +/- 13.1) degrees; the results were excellent in 54 cases, good in 58 cases, moderate in 8 cases, and poor in 2 cases with an excellent and good rate of 92%. In the control group, TAM was (170.0 +/- 15.2) degrees; the results were excellent in 23 cases, good in 30 cases, moderate in 22 cases, and poor in 21 cases with an excellent and good rate of 55%. Significant difference in TAM was found between 2 groups (P < 0.01). CONCLUSION: The microsurgical repair of flexor tendon with non knot Kessler suture method in anastomotic stoma with repair of tendon membrane, tendon sheaths, and the tissue surrounding tendons is more effective than the traditional Kessler suture, but long-term effectiveness still needs further observation. PMID- 22069975 TI - [Effectiveness of in situ subtalar arthrodesis with bone graft for subtalar traumatic arthritis and gait analysis]. AB - OBJECTIVE: To evaluate the effects of in situ subtalar arthrodesis with bone graft for subtalar traumatic arthritis, and to analyse the plantar pressure distribution so as to provide the evidence for effectiveness evaluation. METHODS: Between March 2004 and December 2008, 26 patients with unilateral subtalar arthrodesis undergoing bone graft fusion were enrolled (test group). After operation, the imageology diversity and the effect of subtalar arthrodesis on adjacent joint were observed. American Orthopaedic Foot and Ankel Society (AOFAS) ankle and hindfoot score and radiographs were used to assess the foot function before and after operation. Twenty-six normal subjects served as controls. Foot scan system was used to test the distribution of maximum plantar pressure and the change of gravity center curve. No significant difference was found in gender, age, height, and weight between 2 groups (P > 0.05). RESULTS: All patients were followed up 18.2 months on average (range, 14-71 months). The mean subtalar arthrodesis time was 5.6 months (range, 4 months and 15 days to 11 months). The mean AOFAS ankle and hindfoot score improved from 35.18 +/- 8.16 preoperatively to 76.36 +/- 6.90 postoperatively (t = -13.910, P = 0.000). Nine (34.6%) patients had satisfactory functional effects, and 13 (50.0%) patients basically satisfactory. The talocalcaneal height, talocalcaneal angle, talar declination angle, and calcaneus patch angle were 87.04% +/- 6.17%, 76.73% +/- 5.13%, 65.86% +/- 7.01%, and 70.19% +/- 8.33% of the contralateral side, respectively. Osteoarthritis of the adjacent joints occurred in 7 cases. The maximum plantar pressure increased in the third to fifth metatarsal bones and decreased in the first to second metatarsal bones, showing significant differences when compared with normal controls (P < 0.05). No significant difference was found in the plantar pressure between arthrodesis foot and contralateral foot of the test group (P > 0.05). The plantar pressure was well distributed in patient who was satisfied with the effect, but it was still different from normal controls. In patients who had high plantar pressure in middle foot, mild heel inversion occurred. The gravity center curve of the contralateral foot in the test group was almost the same as that of normal controls; curve medially shifted when forefoot touched down. The curve irregularly and laterally shifted in the subtalar arthrodesis foot; the curve did not medially shift when forefoot touched down. CONCLUSION: In situ subtalar arthrodesis with bone graft has good clinical results for subtalar traumatic arthritis. Gait analysis can be applied to assess the therapeutic effectiveness, and contribute to make a surgical plan. For the adaptive alteration of contralateral side after subtalar arthrodesis, a cohort of normal subjects should be used for comparison in gait analysis. PMID- 22069977 TI - [Effectiveness of a double-tsuge suture method in repairing Achilles tendon ruptures]. AB - OBJECTIVE: To investigate the effectiveness of a double-tsuge suture method with absorbable polydioxanone-cord (PDS-II) in repair of Achilles tendon ruptures. METHODS: Between January 2005 and December 2008, 36 patients suffering from Achilles tendon ruptures were treated operatively. Of 36 patients, there were 29 males and 7 females with a mean age of 36 years (range, 21-50 years), including 22 cases of acute closed injuries, 6 cases of fresh open injuries (the time between injury and hospitalization was 1-10 days, mean 6 days), and 8 cases of old closed injuries (the time between injury and hospitalization was 43-63 days, mean 51 days). The injury reasons were sport injury (25 cases), incised injury (6 cases), falling injury (4 cases), and other (1 case). The results of "heel test" and the Thompson sign were positive in all patients. Operation was performed by using a double-tsuge suture method with a No. 0 PDS-II. After the ankle joint was fixed with short leg plaster cast at 30 degrees plantar flexion position for 6 weeks, the cast was removed and then functional exercises were done. RESULTS: Poor healing of incision occurred in 2 cases of old Achilles tendon ruptures and was cured after symptomatic treatment; healing of incision by first intention was achieved in the others. The patients were followed up 12 to 24 months (mean, 15 months). No rerupture, deep venous thromboembolism, or reflex sympathetic dystrophy occurred during follow-up. When compared with the range of motion of ankle joint of normal side, 7 cases had no change, 16 cases had a loss of 1-10 degrees, 12 cases had a loss of 10-20 degrees, and 1 case had a loss of 25 degrees. The average score was 90 (range, 74-96) according to Termann clinical evaluation criterion; the results were excellent in 24 cases, good in 11 cases, and fair in 1 case, and the excellent and good rate was 97.2%. CONCLUSION: The double-tsuge suture method is easy-to-operate, which has the smallest interference to the blood supply of Achilles tendon because of no crossing or transversal intratendon suture. PDS-II can provide highly strong stability, furthermore, it can be degenerated completely with tiny foreign body reaction, so there is no tendency to develope local adhesion. This technique achieves good results and is associated with a low morbidity of complications. PMID- 22069978 TI - [Computer-aided precise resection of pelvic tumor and function reconstruction]. AB - OBJECTIVE: To investigate the value of computer-aided design (CAD) in defining the resection boundary, reconstructing the pelvis and hip in patients with pelvis tumors. METHODS: Between November 2006 and April 2009, 5 cases of pelvis tumors were treated surgically using CAD technology. There were 3 males and 2 females with an average age of 36.4 years (range, 24-62 years). The cause was osteosarcoma, giant cell tumor of bone, and angiosarcoma in 1 case, respectively, and chondrosarcoma in 2 cases. According to the Enneking system for staging benign and malignant musculoskeletal tumors, regions I, I + II, III, IV, and I + IV is in 1 case, respectively. According to the principle of reverse engineering, 5 patients with pelvis tumors were checked with lamellar CT/MRI scanning, whose two-dimensional data were obtained in disease area. The three-dimensional reconstruction of pelvic anatomical model, precise resection boundary of tumor, individual surgical template, individual prosthesis, and surgical simulation were precisely made by computer with CAD software. Based on the proposal of CAD, the bone tumor was resected accurately, and allograft ilium with internal fixation instrument or allogeneic ilium with personalized prosthetic replacement were used to reconstruct the bone defect after tumor was resected. RESULTS: The operation was successfully performed in 5 cases. The average operation time was 7.9 hours, and the average blood loss was 3 125 mL. Hemorrhage and cerebrospinal fluid leakage occurred in 1 case, respectively, and were cured after debridement. Five patients were followed up from 24 to 50 months (mean, 34.5 months). All patients began non-weight bearing walk with double crutches at 4-6 weeks after operation, and began walk at 3-6 months after operation. Local recurrence developed in 2 patients at 18 months after operation, and resection and radiotherapy were performed. According to International Society of Limb Salvage criteria for curative effectiveness of bone tumor limb salvage, the results were excellent in 2 and good in 3. CONCLUSION: The individual surgical template, individual prosthesis, and surgical simulation by CAD ensure the precision and reliability of pelvis tumors resection. The CAD technology promotes pelvis tumor resection and the reconstruction of pelvis to individual treatment stage, and good curative effectiveness can be obtained. PMID- 22069979 TI - [Application of titanium plate and Teflon patch in chest wall reconstruction after sternal. tumor resection]. AB - OBJECTIVE: To study the reconstruction method and effectiveness of titanium plate and Teflon patch for the chest wall after resection of sternal tumors. METHODS: Between October 2006 and November 2009, 4 patients with sternal tumors were treated and the thoracic cages were reconstructed. There were 2 males and 2 females, aged 30-55 years. The patients were admitted because of chest lump or pain. The sizes of palpable lump ranged from 4 cm x 3 cm to 10 cm x 8 cm. CT examination showed bone destruction. After sternal tumor resection, defect size ranged from 10 cm x 8 cm to 18 cm x 14 cm, and titanium plate and Teflon patch were used to repair and reconstruct the chest wall defect. RESULTS: The operations of the tumor resection and reconstruction of chest wall defect were successfully performed in 4 cases. Incisions healed by first intention with no abnormal breath, subcutaneous emphysema, pneumothorax, and infection. One case failed to be followed up after 6 months; 1 case died of intracranial hemorrhage; and 2 cases were followed up 1 and 4 years respectively without tumor recurrence. The chest wall had good remodeling. No loosening and exposure of titanium plate, difficulty in breathing, chest distress, and chest pain were observed during follow-up. CONCLUSION: Surgical resection of sternal tumors will cause large chest wall defect which can be repaired by titanium plate and Teflon patch because it had the advantages of easy operation, satisfactory remodeling, and less complication. PMID- 22069981 TI - [Comparative study on different pedicles based sural neurofasciocutaneous flaps]. AB - OBJECTIVE: To investigate a best method of obtaining the sural neurofasciocutaneous flap by observing the models of different pedicles based sural neurofasciocutaneous flaps in rabbits and the effect of different pedicles on the survival of the flaps. METHODS: Forty adult New Zealand rabbits (male or female, weighing 2.5-3.0 kg) were randomly divided into 4 groups (10 rabbits in each). The flaps of 7 cm x 1 cm were designed at the lateral hind legs, and the pedicle was 0.5 cm in length. In group A, the flaps were elevated based on a single perforator pedicle; in group B, the flaps were elevated based on fascia pedicle; in group C, the flaps were elevated based on perforator-plus fascia pedicle; and in group D, the flaps were elevated and sutured in situ. At 7 days after operation, the flap survival rate was recorded, and the blood flow in the center of the flap was monitored by laser Doppler flowmetry. The perfusion unit (PU) was measured. RESULTS: After operation, the flaps had no obvious swelling, and the flaps had good color at the proximal end, but pale at the distal end in groups A and B. Obvious swelling was observed with pale color at the distal flaps in group C, but swelling decreased gradually. However, the skin color became dark gradually in group D after operation. The flap survival rates were 74.0% +/- 2.7%, 60.0% +/- 2.5%, 75.0% +/- 3.5%, and 0 in groups A, B, C, and D respectively after 7 days of operation. The PU values were 83.39 +/- 4.25, 28.96 +/- 13.49, 81.85 +/- 5.93, and 8.10 +/- 3.36 in groups A, B, C, and D respectively. There were significant differences in flap survival rates and PU values between groups A, B, C and group D (P < 0.05). Significant differences were found between groups A, C and group B (P < 0.05), but no significant difference between group A and group C (P > 0.05). CONCLUSION: The sural neurofasciocutaneous flap based on a single perforator pedicle has a reliable blood supply and enough venous drainage, which is one of the best methods to obtain the sural neurofasciocutaneous flap. PMID- 22069980 TI - [Reconstruction of severe contracture of the first web space and wrist by incorporating pedicled retrograde flap of forearm transplantation]. AB - OBJECTIVE: To summarize the therapeutic effectiveness of incorporating pedicled retrograde flap of forearm transplantation for reconstructing severe contracture of the first web space and wrist. METHODS: Between November 2005 and February 2010, 26 patients with severe contracture of the first web and wrist were treated. There were 18 males and 8 females with an average age of 27 years (range, 12-45 years). The locations were the right sides in 15 cases and the left sides in 11 cases. The injury reason included hot water scald in 7 cases, explosion hurt in 5 cases, traffic accident in 3 cases, hot pressing in 5 cases, and flame burns in 6 cases. The duration of scar contracture ranged from 6 to 26 months with an average of 11 months. According to the evaluation standard by GU Yudong et al., all had severe contracture of the first web space, and concomitant injuries included adduction deformity thumb, limitation of the thumb extension and opposition function, and carpometacarpal flexion joint deformity. After scar contracture was released, the defect size ranged from 5.8 cm x 4.5 cm to 11.3 cm x 7.2 cm, which were repaired by the incorporating pedicled retrograde flap of forearm of 6.5 cm x 5.0 cm to 12.5 cm x 8.0 cm at size. The donor sites were directly sutured or repaired with skin graft. RESULTS: Blister and partial necrosis occurred at the distal end of the flaps in 2 cases, which were cured after dressing change. The other flaps survived and wounds healed by first intention. Incisions at donor sites healed by first intention. Twenty-six patients were followed up 6 to 24 months (mean, 15 months). The patients had functional recovery in thumb adduction and opposition at different degrees. At 6 months after operation, according to the Swanson et al. AMA system for total thumb activity, the total thumb function was improved significantly, and according to Jensen et al. measurement, the width and angle of the first web space were significantly increased, all showing significant differences (P < 0.05). CONCLUSION: Incorporating pedicled retrograde flap of forearm transplantation for repairing severe contracture of the first web space and wrist could augment the first web space and improve the wrist flexible function. PMID- 22069982 TI - [An experimental study on effect of chitosan/polyvinyl alcohol nerve conduits on peripheral nerve regeneration in macaques]. AB - OBJECTIVE: To investigate the effects of chitosan/polyvinyl alcohol (PVA) nerve conduits for repairing radial nerve defect in Macaques. METHODS: Twelve adult Macaques weighing 3.26-5.35 kg were made the models of radial nerve defect (2 cm in length) and were randomly divided into 3 groups according to nerve grafting, with 4 Macaques in each group. Chitosan/PVA nerve conduit, non-graft, and autografts were implanted in the defects in groups A, B, and C, respectively. And the right radial nerves were used as normal control. At 8 months postoperatively, the general observation, electrophysiological methods, and histological examination were performed. RESULTS: At 8 months postoperatively, the regenerated nerve bridged the radial nerve defect in group A, but no obvious adhesion was observed between the tube and the peripheral tissue. The regenerated nerve had not bridged the sciatic nerve defect in group B. The adhesions between the implanted nerve and the peripheral tissue were significant in group C. Compound muscle action potentials (CMAP) were detected in group A and group C, and no CMAP in group B. Peak amplitude showed a significantly higher value in normal control than in groups A and C (P < 0.05), but there was no significant difference between groups A and C (P > 0.05). Nerve conduction velocity and latency were better in normal control than in groups A and C, and in group C than in group A, all showing significant differences (P < 0.05). The density of myelinated fibers in groups A and C was significantly lower than that in normal control (P < 0.05), but there was no significant difference between groups A and C (P > 0.05). The diameter and the myelin sheath thickness of the myelinated fibers in normal control were significantly higher than those in groups A and C, and in group C than in group A, all showing significant differences (P < 0.05). CONCLUSION: The chitosan/PVA nerve conduits can promote the peripheral nerve regeneration, and may promise alternative to nerve autograft for repairing peripheral nerve defects. PMID- 22069983 TI - [A experimental study on transfecting human stromal cell-derived factor 1alpha and human vascular endothelial growth factor 165 genes into myoblasts in vitro]. AB - OBJECTIVE: To explore the human stromal cell-derived factor 1alpha (hSDF-1alpha) and human vascular endothelial growth factor 165 (hVEGF165) mRNA expressions of the transfected cells after hSDF-1alpha gene and hVEGF165 gene were transfected into rat myoblasts in vitro so as to lay a foundation for further study on the synergistic effects of 2 genes on tissue engineered skeletal muscle vascularization. METHODS: The myoblasts of 1-day-old Sprague Dawley rats were cultured and purified by trypsin digestion assay in vitro and were identified by immunohistochemistry staining of Desmin. Approximately 70%-80% of confluent myoblasts were transfected with enhanced green fluorescent protein (EGFP)-hSDF 1alpha and EGFP-hVEGF165 genes in vitro (transfected group) and were not transfected (control group). The expressions of hSDF-1alpha and hVEGF165 mRNA and protein in the transfected cells were detected by RT-PCR, ELISA, and Western blot respectively. RESULTS: The cultured cells were identified as myoblasts by immunohistochemistry staining of Desmin. The expression of green fluorescent protein was observed in transfected cells, indicating that hSDF-1alpha and hVEGF165 genes were transfected into myoblasts successfully. The mRNA and protein expressions of the 2 genes were positive in the transfected group by RT-PCR and Western bolt assay at 2, 4, 6, and 8 days after transfection, and were negative in the control group. The expressions of hSDF-1alpha and hVEGF165 showed a stable low level in the control group, but the expressions of the proteins increased at 2 days and then showed gradual downtrend with time in the transfected group by ELISA assay. There were significant differences in the expressions of hSDF-1alpha and hVEGF165 proteins between different time points in the transfected group, and between 2 groups (P < 0.05). CONCLUSION: hSDF-1alpha and hVEGF165 genes are successfully transfected into myoblasts in vitro, and mRNA and proteins of hSDF 1alpha and hVEGF165 can be expressed in the transfected myoblasts, which may provide the experimental evidence for the expressions of hSDF-1alpha and hVEGF165 mRNA and proteins in vivo successfully. PMID- 22069984 TI - [Effect of different number of bone marrow mesenchymal stem cells on growth of rat dorsal root ganglia in vitro]. AB - OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs), as replacement cells of Schwann cells, can increase the effect of peripheral nerve repair. However, it has not yet reached any agreement to add the appropriate number of seeded cells in nerve scaffold. To investigate the effect of different number of BMSCs on the growth of rat dorsal root ganglia (DRG). METHODS: Three 4-week-old Sprague Dawley (SD) rats (weighing 80-100 g) were selected to isolate BMSCs, which were cultured in vitro. Three 1- to 2-day-old SD rats (weighing 4-6 g) were selected to prepare DRG. BMSCs at passage 3 were used to prepare BMSCs-fibrin glue complex. According to different number of BMSCs at passage 3 in fibrin glue, experiment was divided into group A (1 x 10(3)), group B (1 x 10(4)), group C (1 x 10(5)), and group D (0, blank control), and BMSCs were co-cultured with rat DRG. The axon length of DRG, Schwann cell migration distance, and axon area index were quantitatively evaluated by morphology, neurofilament 200, and Schwann cells S-100 immunofluorescence staining after cultured for 48 hours. RESULTS: Some long cell processes formed in BMSCs at 48 hours; migration of Schwann cells and axons growth from the DRG were observed, growing in every direction. BMSCs in fibrin glue had the biological activity and could effect DRG growth. The axon length of DRG and Schwann cell migration distance in groups A, B, and C were significantly greater than those in group D (P < 0.05). The axon length of DRG and Schwann cell migration distance in group C were significantly less than those in group B (P < 0.05), but there was no significant difference between group A and group C, and between group A and group B (P > 0.05). The axon area index in groups A and B was significantly greater than that in group D (P < 0.05), but there was no significant difference between group C and group D (P > 0.05); there was no significant difference in groups A, B, and C (P > 0.05). CONCLUSION: In vitro study on DRG culture experiments is an ideal objective neural model of nerve regeneration. The effect of different number of BMSCs in fibrin glue on the growth of DRG has dose-effect relationship. It can provide a theoretical basis for the appropriate choice of the BMSCs number for tissue engineered nerve. PMID- 22069985 TI - [Effect of platelet lysate on chondrogenic differentiation of human umbilical cord derived mesenchymal stem cells in vitro]. AB - OBJECTIVE: To study the effect of platelet lysate (PL) on chondrogenic differentiation of human umbilical cord derived mesenchymal stem cells (hUCMSCs) in vitro. METHODS: Umbilical cords were voluntarily donated by healthy mothers. The hUCMSCs were isolated by collagenase digestion and cultured in vitro. The surface markers of the cells were detected by flow cytometer. According to different components of inductive medium, the cultured hUCMSCs were divided into 3 groups: group A [H-DMEM medium, 10% fetal bovine serum (FBS), and 10%PL]; group B [H-DMEM medium, 10%FBS, 10 ng/mL transforming growth factor beta1 (TGF-beta1), 1 x 10(-7) mol/L dexamethasone, 50 microg/mL Vitamin C, and 1% insulin transferrin-selenium (ITS)]; and group C (H-DMEM medium, 10%FBS, 10 ng/mL TGF beta1, 1 x 10(-7) mol/L dexamethasone, 50 microg/mL vitamin C, 1%ITS, and 10%PL). The hUCMSCs were induced in the mediums for 2 weeks. Toluidine blue staining was used to detect the secretion of chondrocyte matrix. Immunofluorescence method was used to identify the existence of collagen type II. The expressions of Aggrecan and collagen type II were detected by semiquantitative RT-PCR. RESULTS: Flow cytometer results showed that the hUCMSCs did not express the surface markers of hematopoietic cell CD34, CD45, and human leukocyte antigen DR, but expressed the surface markers of adhesion molecule and mesenchymal stem cells CD44, CD105, and CD146. Toluidine blue staining and immunofluorescence showed positive results in group C, weak positive results in group B, and negative results in group A. Semiquantitative RT-PCR showed the expressions of Aggrecan and collagen type II at mRNA level in groups B and C, but no expression in group A. The mRNA expressions of Aggrecan and collagen type II were higher in group C than in group B (P < 0.05). CONCLUSION: Only 10%PL can not induce differentiation of hUCMSCs into chondrocytes, but it can be a supplement to the induced mediums. PL can improve hUCMSCs differentiating into chondrocytes obviously in vitro. This study provides new available conditions for constructing tissue engineered cartilage. PMID- 22069986 TI - [A prospective clinical study on autologous periosteum wrapping tendon allograft for anterior cruciate ligament reconstruction]. AB - OBJECTIVE: To study the effectiveness of anterior cruciate ligament (ACL) reconstruction using autologous periosteum wrapping tendon allograft by comparing with using simple tendon allograft. METHODS: Between March 2008 and November 2008, 68 patients with ACL injury were treated, who were in accordance with the inclusion criteria. They were divided into 2 groups randomly according to different treatment methods: ACL was reconstructed with autologous periosteum wrapping tendon allograft in 31 patients (test group) and with simple tendon allograft (control group) in 37 patients. There was no significant difference in gender, age, disease duration, the cause of injury, and functional score preoperatively between 2 groups (P > 0.05). Anatomic single-bundle ACL reconstruction was performed in 2 groups. RESULTS: Little exudation at tibial tunnel incision was found in 1 case respectively in both groups at 2 weeks after operation and was cured by dressing change and antibiotics. The other incisions healed by first intention. The patients were followed up 24-29 months (mean, 26 months) in the test group and 24-32 months (mean, 27 months) in the control group. CT showed bone tunnel enlargement in both groups at 2 years after operation, but the rate of the tunnel enlargement was less in the test group (5/31, 16.1%) than in the control group (14/37, 37.8%), showing significant difference (chi2 = 3.948, P = 0.047). At 2 years after operation, the results of Lachman test and pivot shift test were negative in 23 cases (74.2%) and 25 cases (80.6%) of the test group, and in 26 cases (70.3%) and 30 cases (81.1%) of the control group, respectively. KT-1000 examination showed the displacement of the test group [(1.74 +/- 0.88) mm] was less than that of the control group [(2.36 +/ 0.83) mm], showing significant difference (t = -2.979, P = 0.004). There was no significant difference in Lysholm score, Hospital for Special Surgery (HSS) score, Tegner score, and International Knee Documentation Committee (IKDC) score between 2 groups at 2 years after operation (P > 0.05). CONCLUSION: Compared with simple tendon allograft, ACL reconstruction with autologous periosteum wrapping tendon allograft can improve tendon-bone healing, and decrease the rate of bone tunnel enlargement, so it has good short-term outcome. PMID- 22069987 TI - [Research progress in immune of composite tissue allotransplantation]. AB - OBJECTIVE: To introduce the research progress in the immune of composite tissue allotransplantation. METHODS: The related articles were reviewed to summarize the immune characteristics, experimental developments, and clinical experiences of composite tissue allotransplantation. Results Composite allogeneic tissue is on the body surface, including the composition of the complex with high antigenicity. There are a lot of differences in the immune responses between composite tissue allotransplantation and organ transplantation, such as immunosuppressant protocol, rejection diagnosis, and chronic rejection. CONCLUSION: In the next study, it is urgently needed to learn these experiences and to establish the special standard of composite tissue allotransplantation in induction of immune tolerance, local medication, and rejection diagnosis. PMID- 22069988 TI - [Research progress in repair and reconstruction of isolated traumatic radial head dislocation with annular ligament injury in children]. AB - OBJECTIVE: To review the research progress in the repair and reconstruction of isolated traumatic radial head dislocation with annular ligament injury in children. METHODS: In recent years, the related literature concerning isolated traumatic radial head dislocation with annular ligament injury in children was reviewed. RESULTS: For isolated traumatic radial head dislocation with annular ligament injury in children, the surgery should be chosen as the main treatment, including open reduction and annular ligament reconstruction surgery. Triceps aponeurosis is usually used as reconstruction materials of annular ligament, mainly because the position of taking material of annular ligament is at the operative incision with less surgery trauma and short operative time; aponeurosis is tough and thick with rigid fixation and low risk of re-dislocation. Artificial materials are paid attention to increasingly because they are easy to get, have rigid fixation, and can avoid operative injury caused by taking material of annular ligament. CONCLUSION: Currently active annular ligament reconstruction surgery should be taken; triceps aponeurosis is widely adopted as reconstruction materials of annular ligament and artificial materials have come to be a new research trend. PMID- 22069990 TI - Water uptake and solubility of Acroseal sealer in comparison with Apexit and AH Plus sealers in Hank's solution. AB - INTRODUCTION: The function of root canal fillings is to seal the root canal system. The important physical property necessary for sealers to achieve this is low solubility. However, any therapeutic effect of calcium hydroxide-based sealers is dependent on the calcium hydroxide being in ionized form, which implies that the material must be at least partly soluble. OBJECTIVE: The objective of our study was to compare weight changes of Acroseal and Apexit, conventional calcium hydroxide-based sealer and AH Plus, epoxy-amine resin sealer in Hank's solution at different exposure times. METHODS: The standardized samples of each material were weighed and immersed in the Hank's solution for 1 h, 24 h, 96 h, 14 days and 28 days. After these exposure times, they were removed, dried, and weighed again. Mean weight changes were determined and the differences between sealers were-analysed statistically using a one-way ANOVA. RESULTS: The highest differences in mass were observed in Apexit, 1.52%, and were significantly different from Acroseal, 0.93% (p<0.05) and AH Plus, 0.45% (p<0.05). There were no significant differences between Acroseal and AH Plus, except for 96 h period. CONCLUSION: Under the conditions of our study, it may be concluded that the Acroseal sealer presented the behaviour more like epoxy-based material, AH Plus, than calcium hydroxide sealer, Apexit. PMID- 22069989 TI - Correlation between ocular pulse amplitude measured by dynamic contour tonometer and colour Doppler flow imaging of the arteric retrobulbar vessels. AB - INTRODUCTION: An altered perfusion of the optic nerve head has been proposed as a pathogenic factor in glaucoma. OBJECTIVE: The aim of this study was to evaluate the correlation between ocular pulse amplitude (OPA), measured by Dynamic contour tonometer (DCT) and colour Doppler imaging (CDI) of the arteric retrobulbar vessels. METHODS: Twenty patients older than 50 years were examined, and divided into two equal groups. The first group comprised of patients with normal tension glaucoma treated with topical antiglaucomatous therapy, and the second group included patients with ocular hypertension and glaucoma suspicious without any antiglaucomatous therapy. Ocular pulse amplitude (OPA) was measured with DCT. CDI was also performed. We measured haemodynamic parameters of the internal carotid artery (ICA), ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCA). Peak systolic (PSV), end-diastolic (EDV) velocities were measured, and resistance index (RI) and pulsatility index (PI) were calculated. RESULTS: Correlation with OPA showed indirect servitude in the RI of the ICA, RI and PI of the CRA, in the first group; and in the PSV and EDV of the ICA, in the RI and PI of the OA, EDV and RI of the CRA, and RI of the PCA, in the second group CONCLUSION: Increase of OPA was mostly followed by the increase of the parameters (PSV, EDV, RI, and PI) of the arteric retrobulbar vessels in the first group; in the second group, increase of OPA was in almost 50% of parameters followed by their decrease. PMID- 22069992 TI - [Long-term follow-up after catheter-ablation of atrioventricular junction and pacemaker implantation in patients with uncontrolled atrial fibrillation and heart failure]. AB - INTRODUCTION: Atrioventricular (AV) junction ablation coupled with pacemaker implantation is an effective therapeutic option for rate control in atrial fibrillation (AF) and heart failure (HF). However, there is controversy regarding the long-term outcome of the procedure, since right ventricular stimulation can lead to left ventricular remodelling and HF. OBJECTIVE: The aim of the study was to determine a 5-year outcome of the procedure on survival, HF control and myocardial function in patients with HF and uncontrolled AF. METHODS: All patients with AF and HF who underwent AV-junction ablation with pacemaker implantation in our institution were followed after the procedure. HF diagnosis was established if > or = 2 of the following criteria were present: 1) ejection fraction (EF) < or = 45%; 2) previous episode of congestive HF (CHF); 3) NYHA class > or = 2; and 4) use of drug-therapy for HF. RESULTS: Study included 32 patients (25 males; 53.4 +/- 9.6 years). The mean heart rate was 121 +/- 25 bpm before and 75 +/- 10 bpm after ablation (p=0.001). Over the follow-up of 5.0 +/- 4.0 years nine patients (28.1%) died (five died suddenly, three of terminal CHF and one of stroke). After the procedure, CHF occurrence was reduced (p=0.001), as well as the annual number of hospitalizations (p=0.001) and the number of drugs for CHF (p=0.028). In addition, NYHA-class and EF were improved, from 3.3 +/- 0.7 to 1.6 +/- 0.8 (p<0.001) and from 39 +/- 11% to 51 +/- 10% (p<0.001), respectively. CONCLUSION: In HF patients with uncontrolled AF, 5-year mortality after AV-junction ablation and pacemaker implantation was 28%. In the majority of these patients good rate of AF and HF control were achieved, as well as the improvement of functional status and myocardial contractility. PMID- 22069991 TI - [Correlation between retention force of experimental plates and viscosity of experimental fluids]. AB - INTRODUCTION: Saliva viscosity plays a significant role in the biophysical segment of the total retention potential of total dentures. OBJECTIVE: The aim of the paper was to establish the dependence of dynamic retention force of experimental plates on experimental fluid viscosity and especially time dependence of these parameters, following at the same time relative changes of the distance between the experimental plate and dentures support established by the dislocation of the experimental plate in both directions. METHODS: For experimental verification we used an original device with the aim to enable in vivo simulation on the phantom made of the upper total denture prosthesis support and experimental plate. The experiment consisted of two parts. In the first part we determined the value of the dynamic retention force with plates without and with achieved ventilation effect. In the second part we determined time dependence of the dynamic retention force of experimental plates on the viscosity of experimental fluids that had been priorly determined on identical samples (8 ml of experimental fluid samples) using a rotational viscometer (Haake RV-12) with a sensor (MV, Germany). RESULTS: Under the conditions of variable viscosity rates of seven experimental fluids (from 0.02 to 1309.04 mPa s), we registered the time dependence of dynamic retention force of the experimental plate related to fluid viscosity during the action of the continual dislocating force of the separating directions. In addition, the maximal height of the dislocation of the experimental plate was registered. The dynamic retention force, manifested by the separating direction of the experimental plate dislocation, was increased concurrently with increased viscosity. CONCLUSION: The increase of dynamic retention force depends directly on medium viscosity. Close border values of fluid viscosity above the investigated ones, the impossibility of experimental layer thinning and the decrease of distance height probably influence the onset of separating dislocation. PMID- 22069993 TI - Asymptomatic cardiovascular manifestations in diabetes mellitus: left ventricular diastolic dysfunction and silent myocardial ischemia. AB - INTRODUCTION: Several cardiovascular manifestations in patients with diabetes may be asymptomatic. Left ventricular diastolic dysfunction (LVDD) is considered to be the earliest metabolic myocardial lesion in these patients, and can be diagnosed with tissue Doppler echocardiography. Silent myocardial ischemia (SMI) is a characteristic and frequently described form of ischemic heart disease in patients with diabetes. Objective The aim of the study was to assess the prevalence of LVDD and SMI in patients with type 2 diabetes, as well as to compare demographic, clinical, and metabolic data among defined groups (patients with LVDD, patients with SMI and patients with type 2 diabetes, without LVDD and SMI). METHODS: We investigated 104 type 2 diabetic patients (mean age 55.4 +/- 9.1 years, 64.4% males) with normal blood pressure, prehypertension and arterial hypertension stage I. Study design included basic laboratory assessment and cardiological workup (transthoracic echocardiography and tissue Doppler, as well as the exercise stress echocardiography). RESULTS: LVDD was diagnosed in twelve patients (11.5%), while SMI was revealed in six patients (5.8%). Less patients with LVDD were using metformin, in comparison to other two groups (chi2 =12.152; p=0.002). Values of HDL cholesterol (F=4.515; p=0.013) and apolipoprotein A1 (F=5.128; p= 0.008) were significantly higher in patients with LVDD. CONCLUSION: The study confirmed asymptomatic cardiovascular complications in 17.3% patients with type 2 diabetes. PMID- 22069994 TI - [Elements of metabolic control in children with type 1 diabetes before and after introduction to insulin analogues]. AB - INTRODUCTION: Diabetes mellitus type 1 (T1DM) in children is characterized by unstable course. A significant number of studies shows that introduction to insulin analogues treatment aims towards better control of the disease. OBJECTIVE: The assessment of metabolic control in children with T1DM that were introduced to insulin analogue treatment after many years of treatment with classic (human) insulin. METHODS: The study included 59 patients 2-19 years old (12.9 +/- 3.8) with T1DM, transferred from treatment with human insulin to insulin analogues treatment. Data were obtained directly from patients and their parents, as well as from medical records. RESULTS: The introduction to insulin analogues treatment, leads to a decrease in the value of glycolized haemoglobin (HbA1c) after 6 months (9.27 +/- 1.68% vs 8.63 +/- 1:26%, p=0.06). Average daily dose of insulin expressed per IU/kg of classic and insulin analogue (1.04 +/- 0.38 vs 1.03 +/- 0.30; p>0.05), remained almost the same. In 39 examinees (66.1%), 6 months before the introduction to insulin analogue treatment, severe hypoglicemia was registered and 6 months after the introduction to insulin analogue treatment it appeared in only two examinees (3.4%) (p<0.001). Ketoacidosis, 6 months before introduction to insulin analogues treatment, appeared in 16 examinees (27.1%), while 6 months after it was not registered (p<0.001). CONCLUSION: The use of insulin analogue treatment in childhood provides adequate metabolic control and substantially reduces the risk of acute complications (severe hypoglicemia, ketoacidosis). PMID- 22069995 TI - [Effect of chromium enriched fermentation product of barley and brewer's yeast and its combination with rosiglitazone on experimentally induced hyperglycaemia in mice]. AB - INTRODUCTION: In the recent years, herbal preparations have been more used to treat diabetes. Dietetic supplement based on barley and beer yeast enriched with chromium (BBCr) is registered in Serbia as a supplement in the treatment of type 2 diabetes. OBJECTIVE: To investigate the effect of the preparation based on barley and brewer's yeast with chromium (BBCr), rosiglitazone (R) and their combination (BBCr+R) on fasting glycaemia and glycaemia in mice after glucose, adrenalin and alloxan application. METHODS: The animals were divided into three groups: glucose 500 mg/kg (I); adrenalin 0.2 mg/kg (II); and alloxan 100 mg/kg (III) and into subgroups according to the substance they received (BBCr: 750 mg/kg, R: 0.75 mg/kg and BBCr+R). Each animal was its own control in respect of glycaemia before and after the treatment with test substances, except for group III which contained a placebo subgroup. RESULTS: BBCr caused a significant decrease of fasting glycaemia and significant reduction of glycaemia after glucose load compared to the values before treatment (7.4 +/- 0.6 mmol/l vs 9.2 +/- 0.6 mmol/l; p=0.01). R and BBCr+R significantly decreased glycaemia after adrenalin load (R: 8.6 +/- 1.8 mmol/l vs 15.4 +/- 3.2 mmol/l; p=0.004; BBCr+R: 9.6 +/- 2.4 mmol/l vs 15.0 +/- 4.4 mmol/l; p=0.04). After alloxan application the glycaemia was significantly lower in the subgroups treated with BBCr, R and BBCr+R compared to placebo subgroup (10.1 +/- 8.0 mmol/l vs 6.8 +/- 2.7 mmol/l vs 13.5 +/- 9.7 mmol/l vs 24.5 +/- 4.7 mmol/l; p=0.001). CONCLUSION: Pretreatment with BBCr caused a significant reduction of fasting glycaemia and glycaemia after glucose load. Rosiglitazone and BBCr+R caused a significant reduction of glycaemia after adrenalin load. Pretreatment with BBCr, R and BBCr+R prevented the onset of experimental diabetes caused by alloxan, which was confirmed by histological analysis of pancreas tissue. PMID- 22069996 TI - Histological types and age distribution of lung cancer operated patients over a 20-year period: a pathohistological based study. AB - INTRODUCTION: Lung cancer is the leading cause of death from malignancy in Serbia. OBJECTIVE: This is a retrospective analysis of lung cancer epidemiological changes regarding to its histological type and patients' age of both genders. Data were based on surgically treated lung cancer patients from 1985 to 2005. METHODS: Data were collected from 972 pathohistological reports of operated patients of both genders divided into age groups. Histological types of lung cancer were distributed in four major groups: squamous cell cancer (SCC), adenocarcinoma (AC), small cell cancer (SCLC) and other rare histological types. Both genders together and separately were analysed. Chi-square with the level of significance p<0.05 and chi-square test for trends were used as statistical methods. RESULTS: SCC predominated in both genders; in 44.7% females and 68.0% males. AC was less frequently diagnosed (21.8%) than SCC (64.0%) in both genders and all age groups. The most frequently operated patients were aged between 51 and 60 years (36.6%) with SCC and AC predominance. Three patients with SCLC were operated in 61-70 age-group. In age-group up to 30 years, three (0.5%) patients were operated on for SCC and other rare lung tumours, respectively. Predominance of other rare lung tumours was established in 51-60 age-group, 25% of patients of both genders. CONCLUSION: SCC is the most frequent histological type of lung cancer found in all age groups and in both genders of surgically treated patients. PMID- 22069997 TI - [Well differentiated endocrine carcinomas of the pancreas]. AB - INTRODUCTION: For the difference from poorly differentiated, well differentiated endocrine carcinomas of the pancreas are the tumours in whom with aggressive surgery and chemotherapy fair results can be achieved. OBJECTIVE: The aim of the study was to point out the importance of such treatment. METHODS: Over a 6-year period eight patients (seven female and one male) of average age 51 years (ranging from 23 to 71 years) were operated on for well differentiated endocrine carcinoma: six of the head and two of the tail of the pancreas. There were two functional and six nonfunctional tumours. Pain in the upper part of the abdomen in seven, mild loss in weight in two, strong heartburn in two, obstructive jaundice in three, diarrhoea in one, sudden massive bleeding from gastric varicosities due to prehepatic portal hypertension caused by pancreatic head tumour in one, and bruise in one patient were registered preoperatively. US and CT in all, angiography in one, octreoscan in two and PET scan in one patient were performed. Whipple's procedure was performed in six and distal pancreatectomy in two patients, as well as systemic lymphadenectomy in all and excision of liver secondary tumours in two patients. In the patient with massive gastric bleeding a total gastrectomy was performed first, followed by Whipple's procedure a month later. RESULTS: R0 resection was achieved in all patients. Lymph nodes metastases were found in six patients. Six patients were given chemotherapy. One patient died 3 years after surgery, seven are still alive, on average 2.5 years. A local recurrence after distal pancreatectomy that occurred 5 years after surgery was successfully reresected and the patient is on peptide-receptor radiotherapy. In other six patients there were no local recurence or distant metastases. CONCLUSION: With aggressive surgery and chemotherapy fair results can be achieved in well differentiated endocrine carcinomas of the pancreas. PMID- 22069998 TI - [Urethral reconstruction in severe hypospadias using buccal mucosa graft and penile skin flap]. AB - INTRODUCTION: Hypospadias represents the most frequent penile anomaly. The most challenging part of hypospadias surgery is urethral reconstruction. Many various tissues are used (local skin flaps, bladder mucosa grafts, buccal mucosa grafts etc.) for the reconstruction of the neourethra. OBJECTIVE: Our aim was to evaluate advantages and disadvantages of combined buccal mucosa graft and penile skin flap in urethral reconstruction in severe hypospadias repair. METHODS: Between December 2005 and August 2009, 48 patients with severe hypospadias, aged from nine months to 12 years (mean age 23 months) underwent surgery. Thirty-four (71%) had penoscrotal and 14 (29%) scrotal hypospadias. Ventral penile curvature was present in all cases, and was corrected by incision of the short urethral plate. Urethroplasty was performed a buccal mucosa graft combined with dorsal penile skin flap. RESULTS: Mean follow-up was 22 months (range from 9 months to 3 years). Satisfactory functional and aesthetic results were achieved in 40 (83%) patients. Fistula was noted in six cases and was solved by minor revision. Urethral stenosis in two cases was resolved by simple dilatation. CONCLUSION: Urethral reconstruction using the buccal mucosa graft and dorsal penile skin flap in severe hypospadias repair could be the method of choice. Using this technique, single stage urethral reconstruction is possible with satisfactory esthetical and functional results. PMID- 22069999 TI - [Physical therapy in the treatment of stress urinary incontinence]. AB - INTRODUCTION: Stress urinary incontinence (SUI) is an involuntary release of urine through the urethra during the increase of abdominal pressure in the absence of m. detrusor contraction. The exercise of pelvic floor muscles is recommended as the first line of cure. It is the least invasive and the only method without any undesirable side effects, which leads to either improvement or complete cure of SUI in 80-85% of cases. OBJECTIVE: The aim of this study was to establish whether the strengthening of pelvic floor muscles using proprioceptive neural facilitation (PNF) spiral dynamic technique was more efficient in comparison to classical Kegel exercise. METHODS: The research was carried out at the Centre for Physical Medicine and Rehabilitation, Clinical Centre Kragujevac. Sixty-six female patients with the symptoms of SUI were monitored in the period of two years. Thirty-four patients did pelvic floor muscle exercises twice a day, in the morning and in the evening, with 15-20 contractions. Thirty-two patients used PNF spiral dynamic technique for strengthening pelvic floor muscles. The patients who used the spiral dynamic technique also did some exercises from the program; they exercised twice a day, in the morning and in the evening, following the prescribed schedule. Treatment outcome was assessed by measuring the pelvic floor muscles by a vaginal dynamometer. RESULTS: The values of the pelvic floor muscle force that were measured using the vaginal dynamometer in both examined groups (PNF spiral dynamic technique or Kegel exercise) were statistically significantly higher after the implemented exercise program (t-test; p=0.000). No statistically significant difference in pelvic floor muscle values was found between the patients who applied PNF spiral dynamic technique and those who did Kegel exercise either before or after the exercise (two-factor analysis of variance with repeated measurements, factor of exercise type; p=0.899). CONCLUSION: Strengthening of pelvic floor muscles by exercises results in a significant increase of pelvic floor muscle strength and reduction of SUI symptoms, regardless of the used exercise program, PNF spiral dynamic technique or Kegel exercise program. PMID- 22070000 TI - [Influence of depression on the quality of life in patients with chronic hepatitis C]. AB - INTRODUCTION: Chronic hepatitis C reduces the quality of life in patients causing fatigue, loss of self-confidence, reduced working capacity, development of depression, emotional problems, and cognitive dysfunction. OBJECTIVE: The aim of the study was to identify the presence of depression in patients with chronic hepatitis C, predicting factors for its expression, and the impact of depression on the quality of life in these patients. METHODS: During the prospective study, we used the Hamilton depression scale to investigate the presence of depression, generic 36-Item Short Form Health Survey (SF-36) and Chronic Liver Diseases Questionnaire (CLDQ) to examine the quality of life in 100 patients with chronic hepatitis C, 30 patients with chronic hepatitis B, 30 patients with chronic liver disease nonviral aetiology and 50 healthy persons. RESULTS: A significantly higher presence of depression, and cognitive dysfunction in patients with chronic hepatitis C were noted as compared to the healthy individuals (p=0.00). In relation to non-viral patients with chronic liver disease, depression was significantly less present (p=0.004). Depression was rare in younger patients. The largest number of patients with chronic hepatitis C was without depression. The presence of depression caused deterioration of the physical and mental components of the quality of life. Multivariate analysis showed that the most significant positive predictive factor for the presence of depression was married life (B=0.278; SE=0.094; p=0.004). CONCLUSION: The presence of depression was more often in patients with chronic hepatitis C viral infection compared to healthy population and was correlated with decline in the quality of life. Depression is more pronounced in the elderly and intravenous drug addicts. The lowest depression is expected in patients who are not married. PMID- 22070001 TI - [Influence of air pollution on birth weight]. AB - INTRODUCTION: Epidemiological studies point out that exposure to air pollution during pregnancy is a risk for low birth weight. OBJECTIVE: The aim of this study was to evaluate the effects of outdoor and indoor air pollution on the occurrence of low birth weight. METHODS: The measurement of outdoor air pollutants, sulphur dioxide and black smoke was carried out daily at the Institute for Public Healthcare of Nis at two measuring locations, in Nis and Niska Banja during 2003. Subjects were 367 pregnant women, nonsmokers and who were not profesionally exposed to air pollution. Data on exposure to source of indoor air pollution (passive smoking and mode of heating) was determined on the basis of a questionnaire. Data on the characterisitics of newborns were taken from the register of Obstetrics and Gyanecology Clinic of Nis. RESULTS: We determined that exposure of pregnant women to outdoor air pollution and wood heating systems had influence on the occurence of low birth weight. Exposure to passive smoking had no influence on neonatal low birth weight. CONCLUSION: Exposure of pregnant women to outdoor and indoor air pollutants can have negative influence on the occurrence of low birth weight. PMID- 22070002 TI - [Syringomyelia in demyelinating disease of the central nervous system: report of two cases]. AB - INTRODUCTION: Syringomyelia is a cavitary extension inside the spinal cord which can be either symptomatic or congenitally-idiopathic. Syringomyelia during the course of the disease in patients presenting with clinically definite multiple sclerosis was described earlier. Syringomyelia in patients presenting with a clinically isolated syndrome suggestive of multiple sclerosis is unusual. CASE OUTLINE: We present two patients presenting with demyelinating disease of the central nervous system with syringomyelia in the cervical and thoracic spinal cord. We did not find classical clinical signs of syringomyelia in our patients, but we disclosed syringomyelia incidentally during magnetic resonance exploration. Magnetic resonance exploration using the gadolinium contrast revealed the signs of active demyelinating lesions in the spinal cord in one patient but not in the other. CONCLUSION: Syringomyelia in demyelinating disease of the central nervous system opens the question whether it is a coincidental finding or a part of clinical features of the disease. Differentiation of the significance of syringomyelia finding in these patients plays a role in the choice of treatment concept in such patients. PMID- 22070003 TI - Identical twins with "mirror image" anisometropia and esotropia. AB - INTRODUCTION: Identical twins account for 0.2% of the world population and 8% of all twins. A "mirror image" variation can be found in 25% of identical twins. Studies of twins assume a special place in human genetics due to the possibility of comparing genetic and other factors. We present two pairs of identical male twins with mirror-image astigmatism and esotropia. CASE OUTLINE: The first was a pair of twelve-year old identical twins with "mirror image" myopic astigmatism. The Twin 1 had myopic astigmatism in the right eye, while the Twin 2 was affected by the left eye myopic astigmatism. The second was a pair of six-year old identical twins with esotropia and hypermetropic astigmatism. The Twin 1 had esotropia in the left eye, while the right eye was affected in the Twin 2. Esotropia was surgically corrected. CONCLUSION: In this study we pointed to the role of genetic factors in the development of refractive error, as well as the type of strabismus. Refraction anomalies (myopia, hypermetropia and astigmatism) are complex heterogeneous disorders and ideal for genetic investigation. The knowledge of genetic mechanisms involved in refractive error susceptibility may allow treatment to prevent progression or to further examine gene-environment interactions. We hope that this paper will initiate further investigation of refraction anomalies in twins and future multicentre studies, which, to our knowledge, have not been conducted in our country so far. PMID- 22070004 TI - [Right-sided aortic arch with anomalous origin of the left subclavian artery: case report]. AB - INTRODUCTION: A right-sided aortic arch is a rare congenital defect of the aorta with incidence of 0.05% to 0.1% reported in published series. Usually it is associated with congenital heart anomalies and esophageal and tracheal compression symptoms. We present a case of a right-sided aortic arch of anomalous left subclavian artery origin, accidentally revealed during multislice CT (MSCT) supraaortic branches angiography. CASE OUTLINE: A 53-year-old female patient was examined at the Outpatients' Unit of the Vascular Surgery University Clinic for vertigo, occasional dizziness and difficulty with swallowing. Physical examination revealed a murmur of the left supraclavicular space, with 15 mmHg lower rate of arterial tension on the left arm. Ultrasound of carotid arteries revealed 60% stenosis of the left subclavian artery and bilateral internal carotid artery elongation. MSCT angiography revealed a right-sided aortic arch with aberrant separation of the left subclavian artery that was narrowed 50%, while internal carotid arteries were marginally elongated. There was no need for surgical treatment or percutaneous interventions, so that conservative treatment was indicated. CONCLUSION: A right-sided aortic arch is a very rare anomaly of the location and branching of the aorta. Multislice CT angiography is of great importance in the diagnostics of this rare disease. PMID- 22070005 TI - Successful retrieval of an unexpanded coronary stent from the left main coronary artery during primary percutaneous coronary intervention. AB - INTRODUCTION: Dislodgement and embolization of the new generation of coronary stents before their deployment are rare but could constitute a very serious complication. CASE OUTLINE: We report a case of a stent dislodgement into the left main coronary artery during the primary coronary intervention of infarct related left circumflex artery in a patient with acute myocardial infarction. The dislodged and unexpanded bare-metal stent FlexMaster 3.0x19 mm (Abbot Vascular) was stranded and bended in the left main coronary artery (LMCA), probably by the tip of the guiding catheter, but stayed over the guidewire. It was successfully retrieved using a low-profile Ryujin 1.25x15 balloon catheter (Terumo) that was passed through the stent, inflated and then pulled back into the guiding catheter. After that, the whole system was withdrawn through the 6 F arterial sheath via the transfemoral approach. After repeated cannulation via the 6F arterial sheath, additional BMW and ATW guidewires were introduced into the posterolateral and obtuse marginal branches and a bare-metal stent Driver (Medtronic Cardiovascular Inc) 3.0x18 mm was implanted in the target lesion. CONCLUSION: Stent dislodgement is a rare but potentially life-threatening complication of the percutaneous coronary intervention. This incident occurring in the LMCA in particular during an acute myocardial infarction requires to be urgently resolved. The avoidance of rough manipulation with the guiding catheter and delivery system may help in preventing this kind of complications. PMID- 22070006 TI - Ileocolic intussusception as a presenting sign of primary lymphoma of the colon. AB - INTRODUCTION: Intussusception is a rare phenomenon in adults. It is caused mainly by malignant neoplasm. Primary lymphoma of the colon is a rare malignancy of the large intestine. The association of intussusception in adult and primary colorectal lymphoma is a diagnostic challenge, since they occur with a variety of atypical symptoms. CASE OUTLINE: We report a case of ileocolic intussusception in a 26-year-old man induced by primary lymphoma of the cecum. He was admitted to our hospital for incomplete intestinal obstruction. After thorough diagnostic work-up (plain abdominal radiography, abdominal ultrasonography, multi-slice computerized tomography, colonoscopy with biopsy), the patient underwent surgery. Intraoperative findings confirmed lymphoma as the cause of intussusception. The right hemicolectomy was carried out with end-to-side ileo-transverse anastomosis. CONCLUSION: Primary colorectal lymphomas should be considered in differential diagnosis of intussusceptions in adults. The treatment of choice is a radical resection where all oncological standards must be fulfilled. PMID- 22070007 TI - Pseudo-Bartter syndrome in an infant with congenital chloride diarrhoea. AB - INTRODUCTION: Pseudo-Bartter syndrome encompasses a heterogenous group of disorders similar to Bartter syndrome. We are presenting an infant with pseudo Bartter syndrome caused by congenital chloride diarrhoea. CASE OUTLINE: A male newborn born in the 37th gestational week (GW) to young healthy and non consanguineous parents. In the 35th GW a polyhydramnios with bowel dilatation was verified by ultrasonography. After birth he manifested several episodes of hyponatremic dehydration with hypochloraemia, hypokalaemia and metabolic alkalosis, so as Bartter syndrome was suspected treatment with indomethacin, spironolactone and additional intake of NaCl was initiated. However, this therapy gave no results, so that at age six months he was rehospitalized under the features of persistent watery diarrhoea, vomiting, dehydration and acute renal failure (serum creatinine 123 micromol/L). The laboratory results showed hyponatraemia (123 mmol/L), hypokalaemia (3.1 mmol/L), severe hypochloraemia (43 mmol/L), alcalosis (blood pH 7.64, bicarbonate 50.6 mmol/L), high plasma renin (20.6 ng/ml) and aldosterone (232.9 ng/ml), but a low urinary chloride concentration (2.1 mmol/L). Based on these findings, as well as the stool chloride concentration of 110 mmol/L, the patient was diagnosed congenital chloride diarrhoea. In further course, the patient was treated by intensive fluid, sodium and potassium supplementation which resulted in the normalization of serum electrolytes, renal function, as well as his mental and physical development during 10 months of follow-up. CONCLUSION: Persistent watery diarrhoea with a high concentration of chloride in stool is the key finding in the differentiation of congenital chloride diarrhoea from Bartter syndrome. The treatment of congenital chloride diarrhoea consists primarily of adequate water and electrolytes replacement. PMID- 22070008 TI - [DiGeorge syndrome: a case report]. AB - INTRODUCTION: DiGeorge syndrome is a genetic disorder caused by deletion of chromosome 22. The main features are congenital heart disease, absence or hypoplasia ofthymus (with consecutive immunodeficiency and infections), hypoparathyroidism with consecutive hypocalcaemia, gastrointestinal problems, Delayed psychomotor development, abnormalities of head and face, tendency to develop seizures and psychiatric disorders. Syndrome can be detected prenatally, or during early development, which is of great importance for preventive and therapeutic measures. Death rate is high during the first year of life, mostly because of congenital heart disease. With prompt diagnosis and treatment most of the children can survive to adulthood, but they are children with special needs requiring continual care and supervision (because of metal retardation, seizures, neurological and psychiatric disorders). CASE OUTLINE: A seven-year-old boy underwent surgical correction of congenital heart disease soon after the birth. Since the age of four years he developed seizures, partially controlled by antiepileptic therapy. Entering the seventh year of age he displayed severe auto and heteroaggressive behaviour. His condition has improved by the introduction of intensive psychiatric and defectological treatment, and daily counselling with his mother the child improved in the sense of calming down, better social communication and acquiring some self-help specific skills. CONCLUSION: Symptoms of DiGeorge syndrome can be detected soon afterthe birth, especially that concerning congenital hearth disease. A prompt diagnosis and surgical intervention can save the child's life. Because of many other symptoms, many diagnostic procedures focused on this syndrome are to be performed, followed by long lasting stimulative treatment and treatment of seizures and psychiatric disorders. PMID- 22070009 TI - [Complications of mechanical ventilation]. AB - Mechanical ventilation of the lungs, as an important therapeutic measure, cannot be avoided in critically ill patients. However, when machines take over some of vital functions there is always a risk of complications and accidents. Complications associated with mechanical ventilation can be divided into:1) airway-associated complications; 2) complications in the response of patients to mechanical ventilation; and 3) complications related to the patient's response to the device for mechanical ventilation. Complications of artificial airway may be related to intubation and extubation or the endotracheal tube. Complications of mechanical ventilation, which arise because of the patient's response to mechanical ventilation, may primarily cause significant side effects to the lungs. During the last two decades it was concluded that mechanical ventilation can worsen or cause acute lung injury. Mechanical ventilation may increase the alveolar/capillary permeability by overdistension of the lungs (volutrauma), it can exacerbate lung damage due to the recruitment/derecruitment of collapsed alveoli (atelectrauma) and may cause subtle damages due to the activation of inflammatory processes (biotrauma). Complications caused by mechanical ventilation, beside those involving the lungs, can also have significant effects on other organs and organic systems, and can be a significant factor contributing to the increase of morbidity and mortality in critically ill of mechanically ventilated patients. Complications are fortunately rare and do not occur in every patient, but due to their seriousness and severity they require extensive knowledge, experience and responsibility by healthcare workers. PMID- 22070010 TI - Histopathology of urinary bladder carcinoma: less common variants. AB - Bladder cancer is a common form of neoplasia which most often presents histologically as urothelial (transitional cell) carcinoma. In this article we review recent publications dealing with the less common variants of urothelial carcinoma such as tumours that show unusual forms of differentiation or the well know squamous, glandular, or sarcomatoid differentiation. Urothelial tumours may also show several distinct growth variants characterized by a nested, micropapillary, lymphoepithelioma-like, or plasmacytoid and giant cell growth pattern.The clinical course of bladder cancer varies depending on the histological type of neoplasia, grade and stage of the tumour. High-grade muscle invasive urothelial cancers and tumours showing variant microscopic morphology have in general high mortality and poor prognosis. PMID- 22070011 TI - [The history of the first pharmacy of Leskovac region]. AB - This paper explains the social and healthcare related conditions in the Leskovac region during 18th and 19th century, and the foundation of the first pharmacy in Serbia. Based on the available historical facts and private documents, the history of the origin and activities of the first pharmacy in the Leskovac region during the Turkish reign in 1862 is presented.The paper also mentions the founder, Dr. Alexiadis (Greek by origin), who was a doctor working in pharmaceutical industry, as well as his son Mgr.Ph. Djordje Aleksic, born in 1847 in Ioannina (Greece) and graduated from the Pharamacy Faculty in Constantinople in 1875, who later became the owner. After graduation, Mgr.Ph. Djordje Aleksic came in Leskovac and took over the "Hipokrat" pharmacy from his father, and started pharmacy business in Leskovac in the true meaning of that word. PMID- 22070012 TI - United States life tables, 2007. AB - OBJECTIVES: This report presents complete period life tables by race, Hispanic origin, and sex for the United States based on age-specific death rates in 2007. METHODS: Data used to prepare the 2007 life tables are 2007 final mortality statistics, July 1, 2007, population estimates based on the 2000 decennial census, and 2007 Medicare data for ages 66-100. The methods used to estimate the life tables for the total, white, and black populations were first used in annual life tables in 2005 and have been in use since that time (1). The methods used to estimate the life tables for the Hispanic, non-Hispanic white, and non-Hispanic black populations were first used to estimate U.S. life tables by Hispanic origin for data year 2006 (2). RESULTS: In 2007, the overall expectation of life at birth was 77.9 years, representing an increase of 0.2 years from life expectancy in 2006. From 2006 to 2007, life expectancy at birth increased for all groups considered. It increased for males (from 75.1 to 75.4) and females (from 80.2 to 80.4), the white (from 78.2 to 78.4) and black (from 73.2 to 73.6) populations, the Hispanic population (from 80.6 to 80.9), the non-Hispanic white population (from 78.1 to 78.2), and the non-Hispanic black population (from 72.9 to 73.2). PMID- 22070013 TI - [Hsp90--a target for anticancer therapy]. AB - Molecular chaperones help other proteins to achieve and maintain their proper conformation. Chaperones bind to newly synthesized or unfolded polypeptide chains, actively modify their conformation and participate on their transport or degradation. Chaperones play an important role in cancer cell, where their increased activity enables stabilization of many mutant proteins and overcoming the stress generated by genetic instability. Hsp90 represents a key chaperone in cancer cells. Growth factor receptors, steroid hormone receptors and signal proctor teins are among its substrates, so-called client proteins; many of them being targets for anti-cancer therapy. Adverse conditions of the tumor microenvironment, such as hypoxia and nutrient deficiency, contribute to destabilization of proteins and further escalate dependence on chaperones. This is why molecular chaperones, in particular Hsp90, may represent a promising target for anticancer therapy. Importantly also, tumour-based Hsp90 has a significantly higher sensitivity to inhibitors than that in normal cells, and Hsp90 activity inhibition in tumours leads to a suppression of cellular signaling in many different oncogenic pathways. Several inhibitors of Hsp90 are currently undergoing clinical evaluation and new agents with different mechanisms of action are continually being identified. PMID- 22070014 TI - [Neoadjuvant chemoradiotherapy of rectal carcinoma with bevacizumab]. AB - Concomitant chemoradiotherapy and radical surgery are standard methods of treatment in patients with locally advanced rectal carcinoma. Neoadjuvant chemoradiotherapy with 5-fluorouracil or capecitabine is considered to be an optimal treatment approach. Clinical studies attempt to facilitate treatment response to neoadjuvant chemoradiotherapy by adding targeted biological therapy. Anti-angiogenic effect of bevacizumab may potentiate radiosenzitivity. We present an overview of standard methods of treatment of rectal carcinoma and a summary of published results of neoadjuvant chemoradiotherapy with bevacizumab in the treatment of rectal carcinoma. At present, this combination is not considered to be a standard procedure of neoadjuvant treatment in the Czech Republic. However, based on the results of forthcoming clinical studies, wider use of this concomitant chemobioradiotherapy in clinical practice can be expected, especially in the treatment of locally advanced stages of rectal carcinoma. PMID- 22070015 TI - [What patients need to know before their breast cancer surgery]. AB - BACKGROUNDS: The quality of health care depends not only on physicians' medical skills but also on proper patient education. The aim of the study was to ascertain the types of information required by women before they start their breast cancer treatment. PATIENTS AND METHODS: Before a surgery, 254 patients with early breast cancer treated primarily by surgery obtained an originally developed questionnaire containing information topics assumed to be important. The patients were asked to indicate the information they had been provided and the information they required. RESULTS: The majority of patients (more than 70%) knew that their disease was malignant, that they needed the surgery and what would be the extent of the resection of their breast. Markedly less patients (47.1%) knew about the planned extent of their regional lymph nodes surgery. More than 80% patients required information about their long-term expectations, such as the overall length of cancer treatment, length and extent of their anticipated physical impairment and their chances for cure. The majority of younger women (76.2%) recommended for total mastectomy required information about breast reconstruction options. A substantial proportion of older women (about 60%) were interested to learn about an anticipated cosmetic outcome and possibilities for correction of their potential defect. CONCLUSION: Multimodal breast cancer treatment is generally managed by clinical oncologists. However, a surgeon should be enabled to discuss with the patient their cancer treatment, what it involves and how it will affect the patient's future life. It is advisable to clarify the extent of the surgery on regional lymph nodes and to engage in discussions on cosmetic outcomes of the surgery. With respect to a proper patient education, breast cancer patients should be treated by surgeons specialized in the treatment of this disease. PMID- 22070016 TI - [Neuroendoscopic biopsy of a brain tumor]. AB - BACKGROUNDS: Neuroendoscopic biopsy is one of the techniques that can be used for histological verification of a suspected brain tumor. The use of neuroendoscopy is particularly useful for cystic tumors and para- and intraventricular brain tumors that are risky for stereotactic biopsy. The technique of navigated neuroendoscopy enables biopsy sampling under visual control, haemostasis of biopsy site and treatment of cerebrospinal fluid pathways obstruction. PATIENTS AND METHODS: Neuroendoscopic technique was used for biopsy in one patient with a solid brain tumor. 23 patients (12 males, mean age 49.7 years, range 21-75 years and 11 females, mean age 59.1 years, range 22-76 years) with a suspected cystic brain tumor underwent neuroendoscopic biopsy. Suspected intra- or paraventricular brain tumor presented indication for neuroendoscopic biopsy in 36 patients (20 males, mean age 43.9 years, range 6-80 years and 16 females, mean age 46.2 years, range 11-78 years). RESULTS: High grade glioma was most frequently diagnosed in patients with cystic brain tumors, followed by low grade gliomas and metastatic tumors. Diagnostic sample was obtained from all patients. Tumor resection was performed in 7 patients with a cystic tumor after neuroendoscopic biopsy and histological findings were identical in 70.1% of them. Similarly, high grade glioma was most frequently diagnosed in patients with intra or paraventricular tumors, followed by tumors originating from pineal region tissues. Diagnostic sample was obtained from 94.3% of patients. Tumor resection was performed in 5 patients after neuroendoscopic biopsy and histological findings of the resected tissue was identical with neuroendoscopic biopsy in 4 of them (80%). CONCLUSIONS: Neuroendoscopy is a safe biopsy technique for a subset of patients who are high risk for the use of stereotactic biopsy, with comparable results. Neuroendoscopy also provides for cerebrospinal fluid circulation obstruction treatment. The use of neuronavigation or stereotactic planning is particularly useful for the planning of an optimal surgical approach, helps to maintain anatomical orientation in distorted anatomy and facilitates haemostasis in case of intraoperative bleeding. PMID- 22070018 TI - [Adaptive IG-IMRT for prostate cancer]. AB - BACKGROUNDS: Adaptive image-guided intensity-modulated radiation therapy (IG IMRT) is a perspective method for the treatment of localized prostate cancer. Validate optimal protocols for IG-IMRT using kilovoltage cone-beam CT (CBCT) are required. PATIENTS AND METHODS: Seventy-six patients with prostate cancer were treated using adaptive IG-IMRT. Based on the CBCT performed during the first 10 fractions of radiotherapy, an average prostate position in relation to the pelvic bones was determined in antero-posterior AP, supero-inferior SI, and right-left axes. An adapted treatment plan for the second phase of the treatment included an isocenter shift into its average position (correction of the systematic error sigma). A margin between a clinical and planned target volume (CTV-PTV) was adjusted according to the magnitude of random error sigma. During the second phase of radiotherapy, set-up of patients was performed daily on pelvic bones using kilovoltage skiagraphic imaging in two projections (kV-kV). Follow-up CBCTs were repeated once a week. RESULTS: An average isocenter position differed from the position of a reference planning CT isocenter in at least one axis in 63 patients (83%). Major changes were recorded in AP axis - shift > or = 2 mm in 33 patients (43%), shift > or = 5 mm in 7 patients (9%). PTV for the second phase of radiotherapy was in the range of 6-10 mm in AP axis, 6-8 mm in SI axis, and 6 mm in RL axis. Mean sigma value in the AP axis was smaller in patients with a specific diet compared to patients without the diet (2.2 mm vs. 2.7 mm, p = 0.05). We evaluated 446 follow-up CBCT images from the second phase of radiotherapy (66 patients had 6 CBCT, 10 patients had 5 CBCT). Set-up error exceeding CTV-PTV margin occurred in 4 cases with no more than once per patient. Safety margin was sufficient in 72/76 patients (95%). CONCLUSION: IG-IMRT protocol integrating CBCT and kV-kV imaging provided adequate coverage of the target volume and proved to be compatible with departmental workflow. Margin reduction around the CTV is a prerequisite for dose escalation aimed at a intraprostatic lesion. PMID- 22070017 TI - Cetuximab enhances the anti-proliferative effect of trastuzumab in ERBB2 over expressing breast cancer cells--preliminary study. AB - BACKGROUND: The tyrosine kinase receptor comprises a subclass of cell surface growth factor receptors. Inhibition of certain members of the Epidermal Growth Factor Receptor (EGFR) family is an effective treatment approach in some cancers. The anti-tumor effects are greater when this approach is combined with inhibition of the ERBB2 receptors. These studies provide novel experimental data demonstrating a significant augmentation of the anti-proliferative effects of monoclonal antibodies (cetuximab and trastuzumab) on human breast carcinoma cell lines with different level of ERBB receptor expression. MATERIALS AND METHODS: Three breast cancer cell lines, MCF-7, BT-474, and SK-BR-3 were used. These are characterised by different levels of EGFR and/or other ERBB family members. Inhibition of cell growth in response to cetuximab, trastuzumab or their combination was assessed by MTT assay. RESULTS: The breast cancer cell lines differed in their sensitivity toTZ, CTX and their combination. The SK-BR-3 cancer cell line was sensitive to TZ. On the other hand, CTX had no effect on BT-474 or on SK-BR-3 that expressed low levels of EGFR and high levels of ERBB2. CONCLUSION: Our new experimental data show that the combination of anti-EGF receptor and anti-ERBB2 mAb may inhibit cancer cells expressing both EGF and ERBB2 receptors. PMID- 22070019 TI - [Partial regression of CNS lesions of Erdheim-Chester disease after treatment with 2-chlorodeoxadenosine and their full remission following treatment with lenalidomide]. AB - INTRODUCTION: Erdheim-Chester disease is a very rare syndrome affecting adult population. It typically causes hyperostosis of long bones, retroperitoneal fibrosis and widening of the aortic wall. Patients frequently suffer from disease associated fevers and pain in the lower limbs. No guidelines are available for the treatment of this rare ailment. Therefore, we describe our experience with lenalidomide in a patient with poor treatment response to 2-chlorodeoxyadenosine. CASE: Diabetes insipidus and neurological problems developing over 4 years were the first signs of the disease. The disease was diagnosed from histology of the bone marrow extracted from the ilium. At diagnosis, the patient had multiple infiltrates in the brain, widened wall of the thoracic and abdominal aorta, fibrotic changes to retroperitoneum and typical hyperostosis of the long bones of lower limbs with high accumulation of technetium pyrophosphate as well as fluorodeoxyglucose. First line treatment involved 2-chlorodeoxyadenosine 5 mg/m2 s.c. for 5 consecutive days every 28 days. There was no clear treatment response identifiable on the MR scan of the brain following the third cycle and thus 4th 6th cycle consisted of 2-chlorodexyadenosine 5 mg/m2 + cyclophosphamide 150 mg/m2 + dexamethasone 24 mg day 1-5 every 28 days. After the 6th cycle, MR showed partial regression of the brain lesions. PET-CT showed an increased accumulation of fluorodeoxyglucose in bone lesions. Second line treatment involved lenalidomide 25 mg/day days 1-21 every 28 days. Lenalidomide tolerance was excellent; the number of neutrophils and thrombocytes was within the physiological range throughout the treatment period. Follow-up MR showed complete remission of the brain lesions, while follow-up PET-CT showed further increase in fluorodeoxyglucose accumulation in the bones of lower limbs. CONCLUSION: Treatment with 2-chlorodeoxyadenosine-based regimen provided partial remission of Erdheim-Chester disease lesions in the brain, while treatment with lenalidomide resulted in complete remission of these lesions. Fluorodeoxyglucose continues to accumulate in the long bones of lower limbs. We are unable to elucidate the reasons for complete remission of the disease in the brain as per the MR and its progression in the long bones according to PET-CT. Further testing of lenalidomide in the treatment of this disease is required to support further use of this perspective treatment option. PMID- 22070020 TI - [Secondary angiosarcomas after conservation treatment for breast cancers]. AB - BACKGROUNDS: The cancerogenic effect of ionizing radiation was documented just several years after it started to be used as a treatment option. Ionizing radiation produces a small but detectable risk of carcinoma as well as bone and soft tissue sarcomas. Over the past 20 years angiosarcomas arising from the area of the irradiated breast have been reported with increasing frequency as the number of women undergoing the breast conserving surgery with consecutive radiotherapy has increased also. Angiosarcomas can originate from either lymphatic or capillary endothelium, namely lymphangiosarcomas and haemangiosarcomas. The most of haemangiosarcomas arising from the breast skin developed in the irradiated area after breast conserving procedure--secondary angiosarcomas. Lymphangiosarcoma is typically associated with longstanding extremity lymphedema--Stewart-Treves syndrome. CASES: We report three cases of angiosarcomas which occured in this region after breast conserving treatment and we also review the literature. CONCLUSION: Paradoxically, the decrease in the use of radiotherapy to the post-mastectomy chest wall and the axillary area is expected to reduce the incidence of angiosarcomas, while the increase in the use of breast conserving procedure plus radiotherapy could lead to increased incidence of angiosarcomas in the residual breast tissue. Special attention should be paid to skin leasions and changes occuring after breast conserving treatment and especially to the ones with the skinthickening. The early detection and diagnosis has the crucial prognostic value. PMID- 22070021 TI - [Metastatic renal cell carcinoma treated with everolimus--data from the RENIS Clinical Registry]. AB - Everolimus is an oral mTOR kinase inhibitor approved for the treatment of patients with metastatic renal cell carcinoma (mRCC) progressing during or after treatment with vascular endothelial growth factor (VEGF)-targeted agents. Using the national RENIS clinical registry, we have retrospectively analysed outcomes of patients treated for mRCC with everolimus. A total of 78 patients were evaluable. Median progression-free survival from the start of everolimus therapy was 7 months (95% confidence interval 2-12 months). Partial response or stable disease was achieved in 69% of patients. Treatment toxicity was predictable and serious adverse events occurred in only 6% of patients the most common being respiratory toxicity. Everolimus therapy provides significant clinical benefit for heavily pretreated mRCC patients after failure of VEGF-targeted therapy. PMID- 22070022 TI - The biomechanics of plate fixation of periprosthetic femoral fractures near the tip of a total hip implant: cables, screws, or both? AB - Femoral shaft fractures after total hip arthroplasty (THA) remain a serious problem, since there is no optimal surgical repair method. Virtually all studies that examined surgical repair methods have done so clinically or experimentally. The present study assessed injury patterns computationally by developing three dimensional (3D) finite element (FE) models that were validated experimentally. The investigation evaluated three different constructs for the fixation of Vancouver B1 periprosthetic femoral shaft fractures following THA. Experimentally, three bone plate repair methods were applied to a synthetic femur with a 5 mm fracture gap near the tip of a total hip implant. Repair methods were identical distal to the fracture gap, but used cables only (construct A), screws only (construct B), or cables plus screws (construct C) proximal to the fracture gap. Specimens were oriented in 15 degrees adduction to simulate the single legged stance phase of walking, subjected to 1000 N of axial force, and instrumented with strain gauges. Computationally, a linearly elastic and isotropic 3D FE model was developed to mimic experiments. Results showed excellent agreement between experimental and FE strains, yielding a Pearson linearity coefficient, R2, of 0.92 and a slope for the line of best data fit of 1.06. FE-computed axial stiffnesses were 768 N/mm (construct A), 1023 N/mm (construct B), and 1102 N/mm (construct C). FE surfaces stress maps for cortical bone showed Von Mises stresses, excluding peaks, of 0-8 MPa (construct A), 0-15 MPa (construct B), and 0-20 MPa (construct C). Cables absorbed the majority of load, followed by the plates and then the screws. Construct A yielded peak stress at one of the empty holes in the plate. Constructs B and C had similar bone stress patterns, and can achieve optimal fixation. PMID- 22070023 TI - The biomechanics of plate repair of periprosthetic femur fractures near the tip of a total hip implant: the effect of cable-screw position. AB - Optimal surgical positioning of cable-screw pairs in repairing periprosthetic femur fractures near the tip of a total hip implant still remains unclear. No studies in the literature to date have developed a fully three-dimensional finite element (FE) model that has been validated experimentally to assess these injury patterns. The aim of the present study was to evaluate the biomechanical performance of three different implant-bone constructs for the fixation of periprosthetic femoral shaft fractures following total hip arthroplasty. Experimentally, three bone-plate repair configurations were applied to the periprosthetic synthetic femur fractured with a 5 mm gap near the tip of a total hip implant. Constructs A, B, and C, respectively, had successively larger distances between the most proximal and the most distal cable-screw pairs used to affix the plate. Specimens were oriented in 15 degrees adduction, subjected to 1000 N of axial force to simulate the single-legged stance phase of walking, and instrumented with strain gauges. Computationally, a linearly elastic and isotropic three-dimensional FE model was developed to mimic the experimental setup. Results showed excellent agreement between experimental versus FE analysis strains, yielding a Pearson linearity coefficient, R2, of 0.90 and a slope for the line of best data fit of 0.96. FE axial stiffnesses were 601 N/mm (Construct A), 849 N/mm (Construct B), and 1359 N/mm (Construct C). FE surface stress maps for cortical bone showed maximum von Mises values of 74 MPa (Construct A), 102 MPa (Construct B), and 57 MPa (Construct C). FE stress maps for the metallic components showed minimum von Mises values for Construct C, namely screw (716MPa), cable (445MPa), plate (548MPa), and hip implant (154MPa). In the case of good bone stock, as modelled by the present synthetic femur model, optimal fixation can be achieved with Construct C. PMID- 22070024 TI - Pre-clinical evaluation of ceramic femoral head resurfacing prostheses using computational models and mechanical testing. AB - Ceramic-on-ceramic hip resurfacing can potentially offer the bone-conserving advantages of resurfacing while eliminating metal ion release. Thin-walled ceramic resurfacing heads are conceivable following developments in the strength and reliability of ceramic materials, but verification of new designs is required. The present study aimed to develop a mechanical pre-clinical analysis verification process for ceramic resurfacing heads, using the DeltaSurf prosthesis design as a case study. Finite element analysis of a range of in vivo scenarios was used to design a series of physiologically representative mechanical tests, which were conducted to verify the strength of the prosthesis. Tests were designed to simulate ideal and worst-case in vivo loading and support, or to allow comparison with a clinically successful metallic device. In tests simulating ideal loading and support, the prosthesis sustained a minimum load of 39 kN before fracture, and survived 10 000 000 fatigue cycles of 0.534 kN to 5.34 kN. In worst-case tests representing a complete lack of superior femoral head bone support or pure cantilever loading of the prosthesis stem, the design demonstrated strength comparable to that of the equivalent metal device. The developed mechanical verification test programme represents an improvement in the state of the art where international test standards refer largely to total hip replacement prostheses. The case study's novel prosthesis design performed with considerable safety margins compared with extreme in vivo loads, providing evidence that the proposed ceramic resurfacing heads should have sufficient strength to perform safely in vivo. Similar verification tests should be designed and conducted for novel ceramic prosthesis designs in the future, leading the way to clinical evaluation. PMID- 22070025 TI - A hip simulator study of metal-on-metal hip joint device using acetabular cups with different fixation surface conditions. AB - In vitro wear data for hip joint devices reported in the literature vary in a wide range from one simulator study to another sometimes for the same type of device tested under identical physiological testing conditions. We hypothesized that non-bearing surface condition of the testing components could be an important factor affecting the simulator wear results. To confirm this hypothesis, fifteen 50 mm metal-on-metal hip resurfacing devices with identical bearing specifications were tested in a ProSim hip wear simulator for 5 million cycles. The heads were standard Birmingham Hip Resurfacing (BHR) heads; whilst the pairing acetabular cups were identical to the standard BHR cup except their different back surface conditions, including: (a) off-the-shelf products after removing the hydroxyapatite (HA) coating; (b) semi-finished products without HA coating; and (c) purposely-made cups without cast-in beads and HA coating. Results showed that the different back surfaces of the cups used indeed caused significantly large variations in the gravimetrically measured wear loss. We postulated that materials loss from the non-bearing surface of the testing components could contribute to the gravimetrically measured wear loss during a wear simulator test both directly and indirectly. The results presented in this paper pertain to In vitro wear simulator study and have little clinical relevance to the performance of any implant in vivo. PMID- 22070026 TI - Reconsideration on the use of elastic models to predict the instantaneous load response of the knee joint. AB - Fluid pressurization in articular cartilages and menisci plays an important role in the mechanical function of the knee joint. However, fluid pressure has not been incorporated in previous finite element modelling of the knee, instead elastic models of the knee are widely used. It is believed that an elastic model can be used to predict the instantaneous load response of the knee as long as large effective moduli for the cartilaginous tissues are used. In the present study, the instantaneous response of the knee was obtained from a proposed model including fluid pressure and fibril reinforcement in the cartilaginous tissues. The results were then compared with those obtained from an elastic model using the effective modulus method. It was found that the deformations and contact pressures predicted by the two models were substantially different. An unconfined compression of a tissue disc was used to help understand the issue. It was clear that a full equivalence between the instantaneous and elastic responses could not be established even for this simple case. A partial equivalence in stress could be conditionally established for a given unconfined compression, but it was not valid for a different magnitude of compression. The instantaneous deformation of the intact tissues in the joint was even more difficult to determine using the effective modulus method. The results thus obtained were further compromised because of the uncertainty over the choice of effective modulus. The tissue non linearity was one of the factors that made it difficult to establish the equivalence in stress. The pressurized tissue behaved differently from a solid material when non-linear fibril reinforcement was presented. The direct prediction of the instantaneous response using the proposed poromechanical model had the advantage of determining the fluid pressure and incompressible deformation. PMID- 22070027 TI - Numerical simulation of bone remodelling around dental implants. AB - Crestal bone loss can result in the failure of dental implants and can be caused, by among other factors, the development of non-physiological mechanical conditions. Bone remodelling (BR) is the physiological process through which bone adapts itself to the mechanical environment. A previously published mathematical model of BR is used in this work to study the homogenized structural evolution of peri-implant bone. This model is used to study the influence of the diameter and length of a dental implant of pure titanium on its long-term stability. The temporal evolution of porosity and microstructural damage of the peri-implant bone are the variables analysed in this study. The results show that damage and porosity increase as the implant length decreases and, more pronouncedly, as its diameter decreases. The increase in damage and porosity levels is localized, as many other studies confirm, at the implant neck due to the stress concentration that is created in that area. The main conclusion of this study is that in implants with a diameter equal to or greater than 3 mm the damage is under control and there is no mechanical failure of the peri-implant bone in the long term. PMID- 22070028 TI - Reduced stress shielding with limited micromotions using a carbon fibre composite biomimetic hip stem: a finite element model. AB - Total hip arthroplasty (THA) enjoys excellent rates of success in older patients, but younger patients are still at risk of aseptic loosening and bone resorption from stress shielding. One solution to the stress shielding problem is to use a hip stem with mechanical properties matching those of cortical bone. The objective of the present study was to investigate numerically the biomechanical performance of such a biomimetic hip stem based on a hydroxyapatite (HA)-coated carbon fibre composite. A finite element model (FEM) of the biomimetic stem was constructed. Contact elements were studied to model the bone-implant interface in a non-osseointegrated and osseointegrated state in the best way. Three static load cases representing slow walking, stair climbing, and gait in a healthy individual were considered. Stress shielding and bone-implant interface micromotions were evaluated and compared with the results of a similar FEM based on titanium alloy (Ti-6Al-4V). The composite stems allowed for reduced stress shielding when compared with a traditional Ti-6Al-4V stem. Micromotions were slightly higher with the composite stem, but remained below 40 microm on most of the HA-coated surface. It is concluded that a biomimetic composite stem might offer a better compromise between stress shielding and micromotions than the Ti 6Al-4V stem with the same external geometry. PMID- 22070029 TI - Correlation between intravesical pressure and prostatic obstruction grade using computational fluid dynamics in benign prostatic hyperplasia. AB - An urodynamic test which measures various physiologic variables during voiding is generally used for accurate diagnosis of a bladder outlet obstruction (BOO) resulting from benign prostatic hyperplasia (BHP). However, this method is difficult to directly apply to all patients because it is an invasive test and many patients suffer from anxiety and embarrassment during the test. Thus, other diagnosis methods such as uroflowmetry and prostatic symptom score are performed to measure the degree of BOO prior to the urodynamic test, and it is necessary to construct a quantitative relationship among the obstruction level, the intravesical pressure, and the uroflow rate. The aim of this paper is to analyse the variation of intravesical pressure as a function of the extent of the obstruction and the uroflow rate from given information on the size of the bladder and the urodynamic test using a computational fluid dynamics approach. In order to analyse the intravesical pressure, a two-dimensional axisymmetric model of the bladder including a narrowed region, i.e. the prostatic obstruction, is created. Then the variation of the intravesical pressure is quantitatively obtained as a function of the magnitude of the uroflow rate and the extent of the obstruction. It is shown that the intravesical pressure significantly increases even for small obstructions and that at large obstructions it can reach values higher than 100 cm H2O, which is a dangerous value. It is shown that the intravesical pressure decreases as the uroflow rate decreases. This study can form the basis of a non-invasive test for the diagnosis of BHP. PMID- 22070030 TI - Application of finite element analysis in pre-operative planning for deformity correction of abnormal hip joints--a case series. AB - In experimental and clinical research, it is difficult to directly measure responses in the human body, such as contact pressure and stress in a joint, but finite element analysis (FEA) enables the examination of in vivo responses by contact analysis. Hence, FEA is useful for pre-operative planning prior to orthopaedic surgeries, in order to gain insight into which surgical options will result in the best outcome. The present study develops a numerical simulation technique based on FEA to predict the surgical outcomes of osteotomy methods for the treatment of slipped capital femoral epiphyses. The correlation of biomechanical parameters including contact pressure and stress, for moderate and severe cases, is investigated. For severe slips, a base-of-neck osteotomy is thought to be the most reliable and effective surgical treatment, while any osteotomy may produce dramatic improvement for moderate slips. This technology of pre-operative planning using FEA can provide information regarding biomechanical parameters that might facilitate the selection of optimal osteotomy methods and corresponding surgical options. PMID- 22070031 TI - Environmental issues and management strategies for waste electronic and electrical equipment. PMID- 22070032 TI - Estimated validity and reliability of on-board diagnostics for older vehicles: comparison with remote sensing observations. AB - Based on requirements under the Clean Air Act Amendments of 1990, most state vehicle inspection and maintenance (I/M) programs have, since 2002, replaced the tailpipe emission testing with the on-board diagnostic (OBD) II testing for 1996 model and newer vehicles. This test relies on the OBD II system to give the pass or fail result, depending on certain conditions that might cause the vehicle to emit pollution 1.5 times higher than the regulated standard. The OBD II system is a computer and sensors installed in the vehicle to monitor the emission control units and signal if there is any malfunction. As a vehicle ages, its engine, pollution control units, and OBD II system deteriorate. Because the OBD II system's durability directly influences the test outcome, it is important to examine the fleetwide trend in the OBD II test results in comparison with an alternative measure of identifying high emitting vehicles. This study investigates whether the validity and reliability of the OBD II test is related to the age of the OBD II system installed in the fleet. Using Atlanta's I/M testing records and remote sensing device (RSD) data collected during 2002-2005, this research establishes the convergent validity and interobserver reliability criteria for the OBD II test based on on-road emissions measured by RSDs. The study results show that older vehicles exhibit significantly lower RSD-OBD II outcome agreement than newer vehicles. This suggests that the validity and reliability of the OBD II test may decline in the older vehicle fleets. Explanations and possible confounding factors for these findings are discussed. PMID- 22070033 TI - Analysis of chemical and physical effects of ultraviolet bulbs on cooking emissions. AB - There is a growing recognition of the risks to health, fire hazard, and air quality from cooking emissions. Recent research has identified what is emitted when foods are cooked. Some of the emitted mass is captured in the exhaust system. The balance is expelled into the atmosphere. The outlet of the exhaust system is a demarcation point-upstream the captured mass is the operator or building owner's concern, whereas downstream into the atmosphere, it affects air quality. Building codes have long required operators to deal with the upstream section. More recently, regulations are being placed on what kitchens can emit to the atmosphere. The industry is responding to this challenge with product innovations. Recently gained understanding of cooking emissions supports much of the innovation-but not all. This paper evaluates the purported benefit of adding better filtration and ultraviolet C (UVC) bulbs in kitchen hoods. A "UV hood" claims a two-step process to reduce emissions: better filters capture more emitted mass, and UVC photons and ozone drive photo-decomposition and oxidation reactions of some of the remaining greasy constituents. Adding UV to a hood at least doubles the cost compared to an equivalent non-UV hood. There is evidence that UV hoods do reduce some emissions. The essential question is whether improved performance is due to UV or relatively inexpensive, improved filters. Experimentation exposed an oleic acid aerosol, representative of cooking emissions, to UVC energy and ozone at higher concentrations and for longer exposure times than can occur in a UV hood. Particle-size and chemical changes were measured on samples collected with UV bulbs off and on. Results strongly indicate little change is happening and most emission reductions are caused by better filtration and not UV. The conclusion is that UV hoods fall short of claimed performance, and unreacted ozone may increase air pollution. PMID- 22070035 TI - Concentrations of particulate matter emitted from large cattle feedlots in Kansas. AB - Particulate matter (PM) emitted from cattle feedlots are thought to affect air quality in rural communities, yet little is known about factors controlling their emissions. The concentrations of PM (i.e., PM2.5, PM10, and total suspended particulates or TSP) upwind and downwind at two large cattle feedlots (KS1, KS2) in Kansas were measured with gravimetric samplers from May 2006 to October 2009 (at KS1) and from September 2007 to April 2008 (at KS2). The mean downwind and net (i.e., downwind - upwind) mass concentrations of PM2.5, PM10, and TSP varied seasonally, indicating the need for multiple-day, seasonal sampling. The downwind and net concentrations were closely related to the moisture content of the pen surface. The PM2.5/PM10 and PM2.5/TSP ratios at the downwind sampling location were also related to the moisture content of the pen surface, humidity, and temperature. Measurement of the particle size distribution downwind of the feedlot with a cascade impactor showed geometric mean diameter ranging from 7 to 18 microm, indicating that particles that were emitted from the feedlots were generally large in size. PMID- 22070034 TI - Characterization of spatial impact of particles emitted from a cement material production facility on outdoor particle deposition in the surrounding community. AB - The objective of this study was to estimate the contribution of a facility that processes steel production slag into raw material for cement production to local outdoor particle deposition in Camden, NJ. A dry deposition sampler that can house four 37-mm quartz fiber filters was developed and used for the collection of atmospheric particle deposits. Two rounds of particle collection (3-4 weeks each) were conducted in 8-11 locations 200-800 m downwind of the facility. Background samples were concurrently collected in a remote area located -2 km upwind from the facility. In addition, duplicate surface wipe samples were collected side-by-side from each of the 13 locations within the same sampling area during the first deposition sampling period. One composite source material sample was also collected from a pile stored in the facility. Both the bulk of the source material and the < 38 microm fraction subsample were analyzed to obtain the elemental source profile. The particle deposition flux in the study area was higher (24-83 mg/m2 x day) than at the background sites (13-17 mg/m2day). The concentration of Ca, a major element in the cement source production material, was found to exponentially decrease with increasing downwind distance from the facility (P < 0.05). The ratio of Ca/Al, an indicator of Ca enrichment due to anthropogenic sources in a given sample, showed a similar trend. These observations suggest a significant contribution of the facility to the local particle deposition. The contribution of the facility to outdoor deposited particle mass was further estimated by three independent models using the measurements obtained from this study. The estimated contributions to particle deposition in the study area were 1.8-7.4% from the regression analysis of the Ca concentration in particle deposition samples against the distance from the facility, 0-11% from the U.S. Environmental Protection Agency (EPA) Chemical Mass Balance (CMB) source-receptor model, and 7.6-13% from the EPA Industrial Source Complex Short Term (ISCST3) dispersion model using the particle-size adjusted permit-based emissions estimates. PMID- 22070036 TI - Application of a combined measurement and modeling method to quantify windblown dust emissions from the exposed playa at Mono Lake, California. AB - Particulate matter < or =10 microm (PM10) emissions due to wind erosion can vary dramatically with changing surface conditions. Crust formation, mechanical disturbance, soil texture, moisture, and chemical content of the soil can affect the amount of dust emitted during a wind event. A refined method of quantifying windblown dust emissions was applied at Mono Lake, CA, to account for changing surface conditions. This method used a combination of real-time sand flux monitoring, ambient PM10 monitoring, and dispersion modeling to estimate dust emissions and their downwind impact. The method identified periods with high emissions and periods when the surface was stable (no sand flux), even though winds may have been high. A network of 25 Cox sand catchers (CSCs) was used to measure the mass of saltating particles to estimate sand flux rates across a 2 km2 area. Two electronic sensors (Sensits) were used to time-resolve the CSC sand mass to estimate hourly sand flux rates, and a perimeter tapered element oscillating microbalance (TEOM) monitor measured hourly PM10 concentrations. Hourly sand flux rates were related by dispersion modeling to hourly PM10 concentrations to back-calculate the ratio of vertical PM10 flux to horizontal sand flux (K-factors). Geometric mean K-factor values (K(f)) were found to change seasonally, ranging from 1.3 x 10(-5) to 5.1 x 10(-5) for sand flux measured at 15 cm above the surface (q15). Hourly PM10 emissions, F, were calculated by applying seasonal K-factors to sand flux measurements (F = K(f) x q15). The maximum hourly PM10 emission rate from the study area was 76 g/m2 x hr (10-m wind speed = 23.5 m/sec). Maximum daily PM10 emissions were estimated at 450 g/m2 x day, and annual emissions at 1095 g/m2 x yr. Hourly PM10 emissions were used by the U.S. Environmental Protection Agency (EPA) guideline AERMOD dispersion model to estimate downwind ambient impacts. Model predictions compared well with monitor concentrations, with hourly PM10 ranging from 16 to over 60,000 microg/m3 (slope = 0.89, R2 = 0.77). PMID- 22070037 TI - Emission factors for high-emitting vehicles based on on-road measurements of individual vehicle exhaust with a mobile measurement platform. AB - Fuel-based emission factors for 143 light-duty gasoline vehicles (LDGVs) and 93 heavy-duty diesel trucks (HDDTs) were measured in Wilmington, CA using a zero emission mobile measurement platform (MMP). The frequency distributions of emission factors of carbon monoxide (CO), nitrogen oxides (NO(x)), and particle mass with aerodynamic diameter below 2.5 microm (PM2.5) varied widely, whereas the average of the individual vehicle emission factors were comparable to those reported in previous tunnel and remote sensing studies as well as the predictions by Emission Factors (EMFAC) 2007 mobile source emission model for Los Angeles County. Variation in emissions due to different driving modes (idle, low- and high-speed acceleration, low- and high-speed cruise) was found to be relatively small in comparison to intervehicle variability and did not appear to interfere with the identification of high emitters, defined as the vehicles whose emissions were more than 5 times the fleet-average values. Using this definition, approximately 5% of the LDGVs and HDDTs measured were high emitters. Among the 143 LDGVs, the average emission factors of NO(x), black carbon (BC), PM2.5, and ultrafine particle (UFP) would be reduced by 34%, 39%, 44%, and 31%, respectively, by removing the highest 5% of emitting vehicles, whereas CO emission factor would be reduced by 50%. The emission distributions of the 93 HDDTs measured were even more skewed: approximately half of the NO(x) and CO fleet-average emission factors and more than 60% of PM2.5, UFP, and BC fleet average emission factors would be reduced by eliminating the highest-emitting 5% HDDTs. Furthermore, high emissions of BC, PM2.5, and NO(x) tended to cluster among the same vehicles. PMID- 22070038 TI - Stabilization and solidification of elemental mercury for safe disposal and/or long-term storage. AB - A simple and highly effective stabilization/solidification (S/S) technology of elemental mercury using only sulfur with paraffin is introduced. First, elemental mercury is mixed with an excess of sulfur powder and heated to 60 degrees C for 30 min until elemental mercury is converted into mercuric sulfide (HgS black, metacinnabar) (Step 1). Then, metacinnabar with additional sulfur is poured into liquid paraffin (Step 2). Finally, the mixture is melted at 140 degrees C and settles to the bottom of the vessel where it cools and solidifies under the layer of liquid paraffin (Step 3). The proposed S/S method with sodium sulfide nonahydrate (Na2S x 9H2O) as an additive is also tested for comparison. The average toxicity characteristic leaching procedure test values are 6.72 microg/L (no additive) and 3.18 microg/L (with additive). Theses concentrations are well below the Universal Treatment Standard (25 microg/L). Effective diffusion coefficient evaluated from accelerated leach test and average headspace concentration of Hg vapor after 18 hr are 3.62 x 10(-15) cm2/sec, 0.55 mg/m3 (no additive) and 5.86 x 10(-13) cm2/sec, 0.25 mg/m3 (with additive). PMID- 22070039 TI - Particulate emissions from a stationary engine fueled with ultra-low-sulfur diesel and waste-cooking-oil-derived biodiesel. AB - Stationary diesel engines, especially diesel generators, are increasingly being used in both developing countries and developed countries because of increased power demand. Emissions from such engines can have adverse effects on the environment and public health. In this study, particulate emissions from a domestic stationary diesel generator running on ultra-low-sulfur diesel (ULSD) and biodiesel derived from waste cooking oil were characterized for different load conditions. Results indicated a reduction in particulate matter (PM) mass and number emissions while switching diesel to biodiesel. With increase in engine load, it was observed that particle mass increased, although total particle counts decreased for all the fuels. The reduction in total number concentration at higher loads was, however, dependent on percentage of biodiesel in the diesel biodiesel blend. For pure biodiesel (B100), the reduction in PM emissions for full load compared to idle mode was around 9%, whereas for ULSD the reduction was 26%. A large fraction of ultrafine particles (UFPs) was found in the emissions from biodiesel compared to ULSD. Nearly 90% of total particle concentration in biodiesel emissions comprised ultrafine particles. Particle peak diameter shifted from a smaller to a lower diameter with increase in biodiesel percentage in the fuel mixture. PMID- 22070040 TI - Rural southeast Texas air quality measurements during the 2006 Texas Air Quality Study. AB - The authors conducted air quality measurements of the criteria pollutants carbon monoxide, nitrogen oxides, and ozone together with meteorological measurements at a park site southeast of College Station, TX, during the 2006 Texas Air Quality Study II (TexAQS). Ozone, a primary focus of the measurements, was above 80 ppb during 3 days and above 75 ppb during additional 8 days in summer 2006, suggestive of possible violations of the ozone National Ambient Air Quality Standard (NAAQS) in this area. In concordance with other air quality measurements during the TexAQS II, elevated ozone mixing ratios coincided with northerly flows during days after cold front passages. Ozone background during these days was as high as 80 ppb, whereas southerly air flows generally provided for an ozone background lower than 40 ppb. Back trajectory analysis shows that local ozone mixing ratios can also be strongly affected by the Houston urban pollution plume, leading to late afternoon ozone increases of as high as 50 ppb above background under favorable transport conditions. The trajectory analysis also shows that ozone background increases steadily the longer a southern air mass resides over Texas after entering from the Gulf of Mexico. In light of these and other TexAQS findings, it appears that ozone air quality is affected throughout east Texas by both long-range and regional ozone transport, and that improvements therefore will require at least a regionally oriented instead of the current locally oriented ozone precursor reduction policies. PMID- 22070041 TI - Perceptual pressures on lenition. AB - The phonological processes known as 'lenition' have traditionally been explained as articulatory effort reduction. However, such a motivation for lenition has never been directly demonstrated; in addition, there are reasons to doubt the articulatory explanation. This paper focuses on a particular type of lenition (intervocalic spirantization of voiced stops) and presents two experiments that investigate what role, if any, perceptual considerations might play in lenition. Experiment I shows that spirantization of intervocalic voiced stops is a less perceptually salient change than devoicing of intervocalic voiced stops (an unattested process). Using the line of reasoning of Steriade's P-map hypothesis, perceptual facts offer an alternative to the articulatory account: lenition of intervocalic voiced stops yields spirants rather than voiceless stops because the latter change is perceptually highly salient. The results of Experiment 2 show that the perceptual facts differ by place of articulation, such that the difference between stops and spirants is greater for labials than for dorsals. These results do not match the attested typology; if anything, languages are more likely to spirantize labials than they are to spirantize dorsals. Thus, perceptual facts have the potential to explain some, but not all, of the typology of lenition. PMID- 22070042 TI - The emergence of an unmarkedness effect in Mandarin speech errors: nasals in a coda position. AB - This study aims to explore how the markedness effect shapes Mandarin slips of the tongue with respect to nasals in syllable-final positions. Data were collected via natural speech and elicitation tasks from 35 participants' reading of 346 test items. Three hundred and eight slips in Mandarin from natural data and 360 slips from elicited data were investigated. This study shows that there exists a strong preference for unmarked coronal nasals over marked dorsal nasals in the syllable-final position in both spontaneous and elicited Mandarin slips. This tendency toward the unmarked [n] reveals that the influence of the unmarkedness effect is present in the coda position in Mandarin slips. Interestingly, this tendency is inconsistent with that found in a previous study by Wan of Mandarin slips in the onset position, which shows a tendency for coronals to be replaced by other sounds. This suggests an onset-coda distinction occurring in Mandarin speech errors, which implies that the markedness effect works differently in distinct syllable positions. More precisely, the unmarkedness effect emerges in the coda position in Mandarin slips, leading to the occurrence of unmarked segments, whereas it submerges in the onset position, resulting in marked segments. PMID- 22070043 TI - Congruent and incongruent semantic context influence vowel recognition. AB - The influence of sentence context on the recognition of naturally spoken vowels degraded by reverberation and Gaussian noise was investigated. Target words were paired to have similar consonant sounds but different vowels (e.g., map/mop) and were embedded early in sentences which provided three types of semantic context. Fifty-eight normal-hearing, young adults were presented with sentences in which acoustic and semantic cues agreed either weakly (neutral) or strongly (congruent) or the cues strongly disagreed (incongruent). One vowel pair (/epsilon/-/ae/) was selected to be easier to recognize than the other (/a/-/ae/). Changes induced in the spectra of the vowels by degradation showed that the impact of reverberation combined with noise was quite different from either condition alone. The recognition performance of participants (n=26) for isolated word stimuli matched the predictions of the frequency analysis. In sentences the recognition of the vowel was strongly influenced by the subsequent context; performance was best with congruent context and worst with incongruent context. The deleterious impact of incongruent context was larger than the helpful impact of congruent context. Incongruent context effects were greatest in noise but were also found in quiet and in reverberation. PMID- 22070044 TI - Acquisition of initial /s/-stop and stop-/s/sequences in Greek. AB - Previous work on children's acquisition of complex sequences points to a tendency for affricates to be acquired before clusters, but there is no clear evidence of a difference in order of acquisition between clusters with /s/ that violate the Sonority Sequencing Principle (SSP), such as /s/ followed by stop in onset position, and other clusters that obey the SSP. One problem with studies that have compared the acquisition of SSP-obeying and SSP-violating clusters is that the component sounds in the two types of sequences were different.This paper examines the acquisition of initial /s/-stop and stop-/s/ sequences by sixty Greek children aged 2 through 5 years. Results showed greater accuracy for the /s/-stop relative to the stop-/s/ sequences, but no difference in accuracy between /ts/, which is usually analyzed as an affricate in Greek, and the other stop-/s/ sequences. Moreover, errors for the /s/-stop sequences and /ts/ primarily involved stop substitutions, whereas errors for /ps/ and /ks/ were more variable and often involved fricative substitutions, a pattern which may have a perceptual explanation. Finally, /ts/ showed a distinct temporal pattern relative to the stop-/s/ clusters /ps/ and /ks/, similar to what has been reported for productions of Greek adults. PMID- 22070045 TI - The effect of age on the acquisition of second language prosody. AB - This study reports an exploratory analysis of the age of arrival (AoA) effect on the production of second language (L2) prosody. Three groups of Mandarin-speaking immigrants (N=10 in each group) with varying AoA in the United States and ten native speakers of English as controls participated in the study. All participants read a paragraph of English, and their speech samples were subjected to three prosodic analyses: speech and articulation rates, native speakers' judgment of the prosody based on segment-filtered speech, and analyses of tones and prosodic groupings using the Mainstream American English Tones and Break Indices (MAE_ToBI) transcription conventions. The L2 groups also filled out a survey providing information about their demographic background, English input, and socio-psychological aspects of language learning. The results revealed that the AoA factor impacted different aspects of prosody to varying degrees. Group differences were statistically significant for speech rate, degree of foreign prosody, the frequency of pitch accents, and the frequency of high boundary tones (H-H%). However,group differences were not significant for articulation rate, prosodic groupings, and the rest of the ToBI-labeled phonological categories. Multiple regression analyses further confirmed the AoA effect on degree of foreign prosody, the frequency of pitch accents, and high boundary tones (H-H%); AoA remained a significant predictor controlling for the effects of other variables. However, speech rate was predicted by English media exposure and motivation variable but not by AoA. PMID- 22070046 TI - The perception of pathologically-disordered phonation by Gujarati, English, and Spanish listeners. AB - This study investigates the influence of linguistic experience on the perception of pathologically-disordered voices using 18 listeners of American English, which has allophonic breathiness, 12 listeners of Gujarati, which contrasts breathy and modal vowels, and 18 listeners of Spanish, which has neither allophonic nor phonemic breathiness. Listeners rated the similarity of pairs of pathologically disordered voices. Multidimensional scaling was used to determine the properties that were most correlated with perception for each listener group. Results showed that Gujaratis' perception was correlated with the difference between the amplitude of the first (HI*) and second (H2*) harmonic (HI*-H2*), which is associated with the production of phonation in Gujarati. English listeners' judgments were correlated with the measure HI*-H2* and cepstral peak prominence, and Spanish listeners' judgments were correlated with HI*-H2 and HI*-AI* (the amplitude of the principal harmonic near the first formant). When compared to Esposito (2006), which asked the same listeners to rate the similarity of breathy and modal vowels from Mazatec, results showed that Gujarati listeners classified the pathologically-disordered stimuli in the same way that they classified the Mazatec stimuli, while English and Spanish listeners perceived the pathologically disordered stimuli and the Mazatec stimuli in slightly different ways. PMID- 22070047 TI - Clinical experience of adnexal torsion: evaluation of 143 cases. AB - We conducted this retrospective study to evaluate the outcomes, indications and post-operative findings of adnexal torsion cases and compared the features of benign cystic teratoma with the other cases. We analyzed a series of 143 cases of adnexal torsion from 2000 to 2009 at current clinic, retrospectively. The data were collected from the patient's specific files and hospital records descriptively. The demographic characteristics, sonographic findings and post operative invention were evaluated. Statistical analyses were carried out by using the statistical packages for SPSS 15.0 for Windows (SPSS Inc., Chicago, IL, USA). A total of 143 cases were operated for adnexal torsion during the study period at our clinic. The clinical and demographic characteristics of the cases are shown in table 1. Of all patients, forty of them were diagnosed as benign cystic teratoma and this group of the adnexal torsion cases had statistically different gravidy, mass size and torsion number from the non-benign cystic teratoma group. Age was not a statistically different between two groups. According to this study, benign cystic teratoma increases risk of adnexal torsion. When detecting benign cystic teratoma the patients should be informed about the risk of torsion and explained the signs of this situation. The early diagnosis and appropriate surgical management of adnexal torsion is the only way to prevent complications and to preserve future fertility. Being aware of the different sonographic findings of torsionated adnexa may assist in the correct diagnosis of these patients. PMID- 22070049 TI - Cost analysis of intra-arterial versus intra-venous delivery of bevacizumab for the treatment of recurrent glioblastoma multiforme. AB - Intra-arterial bevacizumab (IA BV) has been recently identified to be safe in the treatment of recurrent GBM. In this study, we sought to perform a cost analysis of IA BV versus IV BV especially also taking account of patient progression free survival (PFS) and overall survival (OS). We show that IA BV is significantly more cost effective than conventional IV therapy. PMID- 22070048 TI - Zinc is a potential therapeutic for chemoresistant ovarian cancer. AB - Ovarian cancer is the leading cause of death from gynecological cancer. The high mortality rate reflets the lack of early diagnosis and limited treatment alternatives. We have observed a number of properties of zinc cytotoxicity that make it attractive from a therapeutic standpoint. Using SKOV3 and ES2 cells, ovarian cancer cell lines that demonstrate varied degrees of resistance to known therapeutics, we show that zinc killing is time and concentration dependent. Death is preceded by distinct changes in cell shape and size. The effects of zinc are additive with cisplatin or doxorubicin, whose morphological effects are distinct from those of zinc. Cytotoxicity of paclitaxel is minimal, making it difficult to determine additivity with zinc. Paclitaxel results in changes in cell shape and size similar to those of zinc but has different effects on cell cycle progression and cyclin expression. The data indicate that the means by which zinc kills ovarian cancer cells is distinct from currently used chemotherapeutics. Based on the properties reported here, zinc has the potential to be developed as either a primary treatment or as a second line of defense against cancers that have developed resistance to currently used chemotherapeutics. PMID- 22070050 TI - Expressions of CK-19, NF-kappaB, E-cadherin, beta-catenin and EGFR as diagnostic and prognostic markers by immunohistochemical analysis in thyroid carcinoma. AB - Immunohistochemical markers have been proposed for thyroid cancer diagnosis and prognostic studies. Immunohistochemical analysis of CK-19, NF-kappaB, beta catenin, E-cadherin and EGFR were done to evaluate their diagnostic and prognostic efficiencies in eighty eight cancer specimen (PTC-52, FTC-16, benign nodule-12 and MNG-8). CK-19 was positive in 91% (62/68) DTC, 98% (51/52) PTC, 69% (11/16) FTC and 15% (3/20) benign thyroid nodules. NF-kappaB was expressed 93% (63/68) DTC, in 96% (50/52) PTC, 81% (11/16) FTC and 15% (3/20) benign thyroid nodules. Both CK-19 and NF-kappaB were significantly differentiated DTC, PTC and FTC from benign thyroid nodule (p < 0.0001) with diagnostic accuracy of 89.74%, 94.4% and 77.4% for CK-19 and 91.0%, 90.5% and 83.5% respectively for NF-kappaB. Though CK-19 and NF-kappaB were equally sensitive but CK-19 was most specific in the diagnosis of DTC and PTC. The diagnostic accuracy of beta-catenin was 96% and 94% and accuracy of E-cadherin was 90.1% and 93.9% for the diagnosis of metastatic PTC and FTC respectively. EGFR showed 90% (18/20) of metastatic PTC (p < 0.0001) and sensitivity, specificity and accuracy were 90%, 71.8% and 78.85% respectively. CK-19 and NF-kappaB were accurately diagnosed in DTC, PTC and FTC whereas, NF-kappaB, E-cadherin, beta-catenin and EGFR were strongly expressed in invasive papillary thyroid cancers and FTC, thus can be important diagnostic and prognostic marker for FTC and metastatic PTC. This may be concluded that immunohistochemical expression of panel of markers CK-19, NF-kappaB, E-cadherin, beta-catenin and EGFR can be useful in diagnosis and prognosis of DTC. PMID- 22070051 TI - Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation. AB - OBJECTIVE: Prostate cancer is a polyfactorial molecular anomaly that is offering refractoriness against a broad range of therapeutic drugs. Growth factor receptors are actively implicated in oncogenesis. PDGFR/EGFR mediated exacerbated signaling has a central participation and is contributory in fueling the signal transductions that gear up prostate cancer progression. MATERIALS AND METHODS: In this particular study, androgen sensitive, Prostate cancer cell line (LNCaP) was used. Pretreatment of cell line with PDGF resulted in an enhanced proliferation of cells which was evaluated by MTT assay. Treatment of cell line with either alone Curcumin, EGCG, sulforaphane or in combination was evaluated. PDGFR/EGFR activation (phosphorylation) was studied using western blot. RESULTS: Results indicated that phosphorylation was gradually downregulated after treatment with individual compound. However there was a remarkable decrease in cellular proliferation after a combinatorial approach which is indicative of the fact that PDGFR phosphorylation was decreased outstandingly as evaluated by MTT assay. That also gave a prominent decline in the expression and subsequent decrease in proliferation pattern of cells. CONCLUSION: Despite the fact that little is still known regarding the mechanistic insights by which phytonutrients act as barrier to cancer, and attempts to translate the studies from benchtop to bedside are in progress. A detailed analysis of nutraceuticals will help a lot in identifying the stumbling blocks in the standardization of therapeutic interventions. PMID- 22070052 TI - Phellinus rimosus (Berk.) pilat attenuates 7,12-dimethylbenz[a] anthracene induced and croton oil promoted skin papilloma formation in mice. AB - The roles of 7,12-dimethylbenz[a]anthracene (DMBA), a polycyclic aromatic hydrocarbon (PAH), and 12-O-tetradecanoylphorbol-13-acetate (TPA) a skin tumor promoter present in croton oil, are clearly implicated in the formation of skin papilloma. The effect of ethyl acetate extract of Phellinus rimosus, a polypore macro fungus, against croton oil-induced skin inflammation, lipid peroxidation and tumor promotion was studied. The antiinflammatory and lipid peroxidation inhibiting activities were determined by topical application of extract of P. rimosus (10 and 20 mg) prior to the application of 0.1 ml of 50% croton oil in acetone. The tumor promotion inhibiting effect of P. rimosus was evaluated against DMBA-initiated, croton oil promoted two-stage carcinogenesis model in mouse skin. The results showed that topical application of the extract (10 and 20 mg) significantly (p < 0.01) and dose dependently attenuate the inflammatory edema as well as lipid peroxidation induced by croton oil. Similarly, topical application of extract (1 and 5 mg) effectively ameliorated the croton oil promoted skin papilloma formation. The results of this study concluded that ethyl acetate extract of P. rimosus showed antitumor activity against DMBA initiated, croton oil promoted skin papilloma formation which can be partially ascribed to the antiperoxidative and anti-inflammatory effects of the extract. PMID- 22070053 TI - The impact of uterine re-curettage, pre-evacuation and week-one level of hCG on the number of chemotherapy courses in treatment of post molar GTN. AB - BACKGROUND: Post molar GTN was reported to occur in 7.5-20% of patients following evacuation of complete hydatidiform moles and in 2.5-7.5% following evacuation of partial moles. The role of uterine re-curettage in post molar GTN is not clear. OBJECTIVES: Study of the correlation of pre-evacuation and week- one level of hCG, and uterine re-curettage to the number of chemotherapy courses in treatment of post molar GTN. PATIENTS AND METHODS: This retrospective study included 29 cases of post molar GTN through reviewing their medical records. RESULTS: There were 25 cases (86.21) of low risk, and 4 cases of high risk score (13.79%). The 3 year survival was 96.6%. There were non-significant correlation of age, parity, pre-evacuation level and hCG in week-1 to number of chemotherapy courses, while uterine re-curettage was significantly correlated to number of chemotherapy courses (p = 0.04). CONCLUSION: Uterine re-curettage was significantly correlated to less number of chemotherapy courses in patients with post molar GTN (p = 0.04). Pre-evacuation and week-1 hCG were not correlated to number of chemotherapy cycles. A large prospective randomized trial to clarify the beneficial effect of uterine re-curettage is recommended. PMID- 22070054 TI - Avocado fruit (Persea americana Mill) exhibits chemo-protective potentiality against cyclophosphamide induced genotoxicity in human lymphocyte culture. AB - Diets rich in fruits and vegetables have been associated with reduced risks for many types of cancers. Avocado (Persea americana Mill.) is a widely consumed fruit containing many cancer preventing nutrients, vitamins and phytochemicals. Studies have shown that phytochemicals extracted from the avocado fruit selectively induce cell cycle arrest, inhibit growth, and induce apoptosis in precancerous and cancer cell lines. Our recent studies indicate that phytochemicals extracted with 50% Methanol from avocado fruits help in proliferation of human lymphocyte cells and decrease chromosomal aberrations induced by cyclophosphamide. Among three concentrations (100 mg, 150 mg and 200 mg per Kg Body Weight), the most effective conc. of extract was 200 mg/Kg Body Wt. It decreased significant level of numerical and structural aberrations (breaks, premature centromeric division etc. up to 88%, p < 0.0001)), and accrocentric associtation within D & G group (up to 78%, p = 0.0008). These studies suggest that phytochemicals from the avocado fruit can be utilized for making active chemoprotective ingredient for lowering the side effect of chemotherapy like cyclophosphamide in cancer therapy. PMID- 22070055 TI - Characterization of a murine lung adenocarcinoma (LAC1), a useful experimental model to study progression of lung cancer. AB - Lung cancer is one of the most important avoidable causes of death around the world, the most widespread carcinoma, with a very poor prognosis, and is the leading cause of cancer death in both developed and developing countries. We report morphological and biological behavior characteristics of a tumor that arose in only one BALB/c mouse of an experimental group treated with urethane, a chemical lung-tumorigenic agent. Morphological and immunochemical analysis indicated phenotypic compatibility with a lung adenocarcinoma. The tumor was named LAC1 (lung adenocarcinoma 1). Implant success in eight LAC1-bearing mice generations was 100%, with a fast evolution (58 survival days) and good metastatic capacity (41% of animals with metastases). The tumor induced a paraneoplastic syndrome characterized by anemia, neutrophilia, cachexia, splenomegaly and thymic atrophy. The lymphoproliferation to Con A was altered in tumor-bearing mice. This lung adenocarcinoma may be a useful experimental model for studying tumor progression, paraneoplastic syndromes and immunology in carcinogenic studies. PMID- 22070056 TI - CD22 as a target for cancer therapy. AB - Targeted therapies with monoclonal antibodies have been increasingly incorporated into the treatment for both lymphoid and myeloid hematological malignancies. Rituximab, the first approved monoclonal antibody for the treatment of cancer, has revolutionized our approach to the management of chronic lymphocytic leukemia and non-Hodgkin's lymphoma. However, there is still an unmet medical need for novel therapeutic approaches, especially for patients in the relapsed/refractory setting. Therapeutic agents with specificity against different surface antigens on malignant B cells hold promise for improving clinical outcome in these patients. Throughout the last decade, CD22, a B-cell-restricted phosphoglycoprotein of the immunoglobulin superfamily, has gained considerable interest as a therapeutic target for B-cell-directed therapies. Several novel therapeutic agents that selectively target CD22 are being developed as an alternative approach for cancer treatment. This review summarizes the current knowledge of CD22 and discusses the rationale for targeting CD22 in B-cell malignancies with immunotherapeutic agents. This review also describes some of the most promising investigational anti-CD22 agents for the treatment of B-cell malignancies. PMID- 22070057 TI - In vitro studies on Bothrops venoms cytotoxic effect on tumor cells. AB - BACKGROUND: Animal venoms are complex mixtures of proteins and non proteins components with several biological activities. Snake venoms represent an essentially unexplored source of bioactive compounds that may cure disease conditions which do not respond to currently available therapies. These venoms possess many pharmacological activities, as cytotoxic and/or lytic effects on tumor cells in vitro. Herein, were investigated the in vitro cytotoxicity of three Bothrops venoms in tumor cell lines. METHODS: Cytotoxic effect was evaluated in HCT-8 (colon - human), SF-295 (nervous system - human), HL-60 (human leukemia) and MDAMB-435 (breast - human). Cell density and membrane integrity were determined by the exclusion of propidium iodide. To determine whether Bothrops venoms treated cells were undergoing an apoptotic and/ or necrosis death, phosphatidylserine (PS) externalization was measured after the incubation with the venom. RESULTS: Botrhops venons showed significant cytotoxcity against all cell lines in study. Cell density and membrane integrity were determined by the exclusion of propidium iodide. The Bothrops venoms reduced the cell number and revealed the presence of a necrotic population when the cells was exposed to the B. pauloensis B. diporus and B. pirajai venoms. To determine whether Bothrops venoms treated cells were undergoing an apoptotic and/or necrosis death, PS externalization was measured after the incubation with the venom and it was observed necrotic and apoptotic cells. CONCLUSIONS: All Bothrops venoms tested showed cytotoxicity against tumor cell lines through inducing of necrosis and apoptosis. PMID- 22070058 TI - Assessing the current status of tobacco dependence education curricula in U.S. physician assistant programs. AB - PURPOSE: Tobacco use continues to be the single most preventable cause of death and disease in the United States. A paradigm shift is needed in physician assistant (PA) education to address tobacco dependence as a chronic, relapsing disease requiring patient education, counseling, treatment, and follow-up. METHODS: A national study was conducted to assess the existing tobacco dependence education currently offered in U.S. PA programs. An established tobacco dependence curriculum survey was revised and mailed to the 141 accredited PA programs in the United States during the 2008-2009 academic year. The survey asked respondents to report the following with regard to tobacco dependence education content in their PA program; (1) Perceived self-efficacy and barriers; (2) Medical topics covered and minutes spent; (3) Evaluation of students' competency level; (4) Tobacco courses, topics, and resources used; and (5) Level of tobacco-cessation competency expected upon graduation. RESULTS: A total of 79 surveys were returned (56% response rate). Though, on average, over 827 minutes (14 hours) were devoted to tobacco dependence education curriculum, most minutes (223 minutes) were spent on the health effects of tobacco use, with only 42 minutes spent on cessation counseling, 55 minutes on medications, and 13 minutes on integrating tobacco-cessation into clinical practice. CONCLUSIONS: PA educators have the unique opportunity to affect tobacco-related morbidity and mortality. The present study demonstrates that PA instructors are more than adequately teaching students about tobacco use. However, it is not clear if students are being adequately taught how to assist patients to quit using tobacco. PMID- 22070059 TI - Screening applicants for risk of poor academic performance: a novel scoring system using preadmission grade point averages and graduate record examination scores. AB - PURPOSE: The purpose of this study was to develop an effective screening tool for identifying physician assistant (PA) program applicants at highest risk for poor academic performance. METHODS: Prior to reviewing applications for the class of 2009, a retrospective analysis of preadmission data took place for the classes of 2006, 2007, and 2008. A single composite score was calculated for each student who matriculated (number of subjects, N=228) incorporating the total undergraduate grade point average (UGPA), the science GPA (SGPA), and the three component Graduate Record Examination (GRE) scores: verbal (GRE-V), quantitative (GRE-Q), analytical (GRE-A). Individual applicant scores for each of the five parameters were ranked in descending quintiles. Each applicant's five quintile scores were then added, yielding a total quintile score ranging from 25, which indicated an excellent performance, to 5, which indicated poorer performance. RESULTS: Thirteen of the 228 students had academic difficulty (dismissal, suspension, or one-quarter on academic warning or probation). Twelve of the 13 students having academic difficulty had a preadmission total quintile score 12 (range, 6-14). In response to this descriptive analysis, when selecting applicants for the class of 2009, the admissions committee used the total quintile score for screening applicants for interviews. Analysis of correlations in preadmission, graduate, and postgraduate performance data for the classes of 2009-2013 will continue and may help identify those applicants at risk for academic difficulty. CONCLUSION: Establishing a threshold total quintile score of applicant GPA and GRE scores may significantly decrease the number of entering PA students at risk for poor academic performance. PMID- 22070060 TI - Assessing the value of dual physician assistant/public health degrees. AB - The popularity of dual physician assistant/master of public health degree programs continues to increase within US physician assistant (PA) education. The advantages and disadvantages of pursuing dual degree training have not been fully explored in the PA literature. Potential advantages of dual training include broadening of the student's perspective on health and health care beyond the "one provider, one patient" medical model, increased training in evaluation and use of the medical literature, increased skill in assessing community factors that affect the health of patients, enhanced expertise in health care administration or policy, and improved prospects for future roles as PA faculty members. Potential drawbacks include increased duration and expense of PA/MPH education, student burnout due to prolonged training, and the lack of jobs that explicitly use both halves of the PA/MPH training. PMID- 22070061 TI - A study of predictive validity of physician assistant students' reported practice site intent. AB - PURPOSE: With the downward trend in numbers of primary care physicians, it is anticipated that mid-level providers will increasingly fill the resulting void in rural health care. Recruitment of health care providers into rural areas has been historically difficult, and West Virginia has been at the forefront of developing programs to address rural recruitment. One of these programs is the West Virginia Rural Health Education Partnership, which provides rural clinical rotation opportunities for students from multiple disciplines and schools in West Virginia. This study assessed the predictive validity of physician assistant (PA) students' prediction, after completion of rural rotations, of a rural or an urban practice site and also assessed for factors associated with subsequent rural practice. METHODS: The Institutional Review Board of West Virginia University approved this study. The West Virginia Rural Health Education Partnership's electronic database, which has collected students' postrotation evaluation information since 2001, was coupled with West Virginia licensing information that included information on PA practice site(s). Data on 168 practicing West Virginia PAs who had completed rural rotation questionnaires during their clinical education were examined. Designation of a rural or an urban practice site was done using rural-urban commuting area codes. RESULTS: Student prediction of rural practice was significantly associated with subsequent rural practice (P < 0.04). Variables most predictive of rural practice were student reporting of high school hometown as rural and of West Virginia practice intent. CONCLUSIONS: This study suggests moderate predictive validity of PA student reporting on rural practice and on West Virginia practice intent; such methods may have potential in prediction of the future rural PA workforce. PMID- 22070062 TI - Essentials of corporate governance. PMID- 22070063 TI - The evidence-based medicine write-up: a tool for EBM skill development and patient-centered evidence application. PMID- 22070064 TI - Une Lecon Clinique a la Salpetriere (A clinical lesson at the Salpetriere), Andre Brouillet (1887). PMID- 22070065 TI - Strategies for workplace learning used by entry-level physician assistants. AB - PURPOSE: Physician assistants (PAs) play an increasingly important role in medicine. While PAs have strong basic science and clinical training in school, typically they don't participate in postgraduate training and are expected to expand their generalists' competencies through continuing professional education. The purpose of this study was to investigate the methods PAs use during their initial phase of workplace learning and determine which methods are deemed most effective by PAs. METHODS: This large, cross-sectional study of PAs within the first 2 years of practice consisted of a survey of PAs investigating the methods used for assessment of educational needs, instruction, and assessment of learning. RESULTS: The results revealed that PAs generally found that employers are well aware of their learning needs and their supervising physicians play an essential role in their learning. PAs themselves often recognized their learning needs based on perceived gaps in competencies noted with patient encounters. Though many PAs reported having an orientation period, most PAs said that this orientation was not well adapted to their unique learning needs. A variety of methods were used during workplace learning, with those related to real patient problems deemed most helpful by PAs. Although PAs reported that their learning was assessed, review of patient outcome data was uncommon. CONCLUSIONS: Consistent with principles of adult learning theory, these findings suggest that PAs find active forms of learning most valuable. Employers and supervising physicians should consider these findings and the available literature on adult learning in developing an environment that is supportive of continuing professional development. PMID- 22070066 TI - The use of multimedia clinical case scenario software in a problem-based learning course: impact on faculty workload and student learning outcomes. AB - PURPOSE: The purpose of this study was to assess the effect of using multimedia clinical case scenario software in lieu of text-based problem-based learning (PBL) cases. The specific interests in this study were student learning outcomes and facilitator utilization. METHODS: The study was conducted with one cohort of 39 physician assistant (PA) students using the seven text-based PBL cases and adding one DxR Clinician software case. Faculty members facilitated each case. A second cohort of 41 PA students completed a blended curriculum of four PBL text cases and four DxR Clinician cases, including the same case used by the first cohort. The students' clinical reasoning case scores for each cohort were compared using a two-tailed unpaired t-test. During the second cohort's use of the DxR clinician cases, facilitators were available to the students upon request. Facilitator hours for each case in both cohorts were tabulated. A quantitative analysis of faculty time commitment was performed comparing the cohorts using a paired t-test. RESULTS: The clinical reasoning score between cohorts increased 12% with the increased use of multimedia clinical case scenario software. The savings in faculty facilitator time was 41% using the blended curriculum of text-based cases and multimedia cases. This time savings could potentially rise to 92% using multimedia cases exclusively. CONCLUSIONS: The use of multimedia clinical case scenario software offers an exciting opportunity to encourage clinical reasoning skills using an updated format for PBL. Additionally, the faculty time savings due to decreased PBL facilitation would allow more programs to incorporate PBL into their curriculum. PMID- 22070067 TI - [The significance of the expression of Col IV and LN in nasal and paranasal sinus malignant tumor]. AB - OBJECTIVE: To study the pathological relationship between the expression of Col IV and LN in nasal and paranasal sinus malignant tumor (NPMT). METHOD: The immunohistochemical technique was used to detected the expression of Col IV and LN in NPMT, para-cancer tissues and non-cancer tissues. RESULT: There was a significance on the expression of the Col IV and LN in NPMT, para-cancer tissues and non-cancer tissues (P<0.01), and no significance in endepidermis and soft connective tissue of the NPMT (P>0.05). CONCLUSION: The Col IV and LN perhaps participate in tumorigenesis of NPMT, and may play the homoioplastic role in different pathological types of the NPMT. PMID- 22070068 TI - [Aeroallergen spectrum of patients with child allergic rhinitis in Changsha area of China]. AB - OBJECTIVE: To investigate aeroallergen spectrum and allergy positive rates of patients with child allergic rhinitis and analyze its related factors. METHOD: Skin prick test was carried out in 562 cases with child allergic rhinitis using 13 inhaled allergens, and detailed history was collected in all cases. RESULT: Four hundred and fifty-seven (81.3%) of 562 cases showed positive reaction to at least one allergen out of 13 allergens. The most common allergens found in patients was Dermatophagoides farinae and Dermatophagoides pteronyssinus, and positive reaction was 93.1% in child allergic rhinitis, followed by tropical mite, Periplaneta americana, Blattella germanica and dog hair. The pollen allergen, most common in American and European, was pretty rare in this study. The prevalence of child allergic rhinitis was significantly higher in urban than in rural (P<0.01). There was no adverse effect appeared in children with allergic rhinitis underwent skin prick test. CONCLUSION: The major allergen of allergic rhinitis is mite for child allergic rhinitis, and relates to housing enviroment. Most of patients with child allergic rhinitis can be treated by the mite specific immunotherapy. The skin prick test is a safe technique for diagnosis of children with allergic rhinitis. PMID- 22070069 TI - [Application of image guidance system in endoscopic optic nerve decompression of traumatic occlusion optic neuropathy affiliated with cerebrospinal rhinorrhea]. AB - OBJECTIVE: To investigate the advantages of image guidance system in endoscopic optic nerve decompression of traumatic occlusion optic neuropathy affiliated with cerebrospinal rhinorrhea. METHOD: Retrospective review of 15 traumatic occlusion optic neuropathy affiliated with cerebrospinal rhinorrhea at our department between June 2006 and June 2010. Witch were performed endoscopic optic nerve decompression and cerebrospinal rhinorrhea euplastic by image guidance system. RESULT: After 3 months to 1 year follow-up, All the cases with cerebrospinal rhinorrhea euplastic were successful. Two cases recovered to 0.3-0.6 in visual activity. Two cases to 0.1-0.3. One case was less than 0.1. Two cases could see hand movement and 2 cases had light perception. Total effective rate was 60 percent (9/15). CONCLUSION: Image guidance system combined with endoscopy provides accurate localization and identifies the operative borders and critical anatomical structure of skull base, optic nerve and internal carotid artery,and also clearly indicate their adjacent relations,also decreases surgical invasions and complications. Image guidance system can improve the accuracy and safety, particularly in local anatomic structure due to the trauma caused by changes in the relationship. It is a safety and effective therapy method. PMID- 22070070 TI - [Study of acoustic rhinometry and rhinomanometry for severe obstructive sleep apnea-hypopnea syndrome]. AB - OBJECTIVE: To study the relationship between nasal airway function and severe obstructive sleep apnea-hypopnea syndrome (sOSAHS). METHOD: One hundred and four cases were divided into 3 groups: group A was 39 normal adult men, group B was 25 nonobese patients with sOSAHS (BMI<28), groups C was 40 obese patients with sOSAHS (BMI > or = 28). Acoustic rhinometry and rhinomanometer was used to acquire unilateral area of first constriction, unilateral area of second of constriction, unilateral minimum cross-sectional area,unilateral nasal volume 0-5 cm, 2-5 cm, the effective unilateral and total nasal resistances in inspiration, expiration at 150 Pa (URins, URexp, TRins, TRexp). RESULT: Nasal resistance were significantly higher in the group B compared to the group A and group C (P<0.05). Among the group B, but not the group A and group B, we found significant correlations between TRins,TRexp and apnea hypopnea index (r=0.402, 0.401, P<0.05). CONCLUSION: Nasal resistance is an important factor for nonobese patients with sOSAHS. PMID- 22070071 TI - [The clinical characters and acoustic rhinometry analyses of 98 cases fugal ball sinusitis]. AB - OBJECTIVE: To improve the cognition of fungal ball sinusitis (FB) for diagnosing and treatting it rightly, we retrospectively analyzed the hospitalization cases. METHOD: We analyzed 98 cases FB patients' first symptom, acoustic rhinometry, CT manifestation, operation fashion. RESULT: The first symptoms of FB include: 47.2% nosebleed, 38.8% snuffle, 28.6% headache and face-ache, 4.0% nasal peculiar smell, 2.0% excessive tear, 4.0% no symptom. Anterior nasoscope inspection include: 43.9% no significant abnormity, 13.3% nasoseptal deviation. 41.8% nasal cavity neoplasm (nasal polyp, nasoturbinal polyp, nasal meatus fugal ball etc), 25.5% secretion in nasal cavity. The parameters that conclude the nasal airway resistance (NAR), nasal cavity volume (NCV) and nasal minimal cross-section area (NMCA) have extremely difference (P<0.01) between FB and normal volunteers (NV): the NAR increase, but NCV and NMCA decrease; the Distance of the Minimal cross sectional area from the nostril (DCAN) appear moving backword compared with NV. The CT manifestation: almost unilateral lesions, involved paranasal sinuses present asymmetric or symmetrical opacification: 60.2% with calcified area, 25.5% with local bone erosion, 74.5% with sinus wall sclerosis. 65.3% of the CT diagnoses as FB are accord with pathology diagnoses. The incidence of FB involve maxillary sinus most (54.1%), then sphenoid sinus (11.2%) and ethmoid sinus (5.1%), frontal sinus (2.0%), multi-sinus (32.7%). All cases operated functional endoscopy surgery: 13 cases with nasoseptal diorthosis, 4 cases with inferior meatus opening, 2 case with canine fossa opening; we clean up the fungal pathogen with different degree endoscope through different path. CONCLUSION: The clinical symptom of FB is not representative; the acoustic rhinometry show that NAR increasing but NCV and NMCA decreasing maybe the reason of fungal infection; the CT examine is helpful for FB diagnosis; the functional endoscopy surgery is efficient therapy for FB. PMID- 22070072 TI - [To investigate the relationship of airborne fungi and allergic disease of respiration system in the city of Wuhan region]. AB - OBJECTIVE: To investigate the relationship between the prevalent species and the seasonal drift law of airborne fungi and respiratory allergic disease in the city of Wuhan. METHOD: Airborne fungi was investigated by exposed sides from 2007 to 2008, and 1674 patients with respiratory allergic disease that were used to do allergens skin test simultaneously, in order to analyze the simultaneous. RESULT: Airborne fungi could be detected in air all over the year. In 2007, the exposed films collected 26 734 fungi spores, and 686 other fungi (hypha and not well known fungi), to the sum of 27420. Otherwise, in 2008, the exposed films collected 26 531 fungi spores, and 730 other fungi, to the sum of 27 261. In the survey, 17 types of species of the collected fungi spores were identified, and the predominant species were alternaria sp, ustilaginales, deightoniella sp, uredinales, and the quantity of Fungi alternaria was most of all . And the peak period mainly concentrated from April to June, and from September to October. Otherwise, the positive rate of fungi skin test in patients with respiratory allergic disease was 10.48% in 2007, but 10.07% in 2008. The main period of onset of respiratory allergic disease was from April to June, and from September to October, similar as the seasonal drift law of airborne fungi. CONCLUSION: The period of onset of respiratory allergic disease was consistent with the seasonal drift law of airborne fungi. PMID- 22070073 TI - [The analysis on the allergen test of the allergic rhinitis with 1564 cases in Changji district]. AB - OBJECTIVE: To investigate the allergen distribution of subjects suffered from the allergic rhinitis in Changji district. METHOD: Skin prick test was employed on all the 1 564 sufferers by 17 sorts of allergic stock solution, with the physiological saline to be the negative control and the histamine to be the positive control. RESULT: The positive rate of allergen citanest was 85.17%. Furthermore, Chenopodium and Lupulus, as the main allergen substances, were found out to be the highest positive rate among 1332 subjects who were detected to be positive, with pollen of trees following. Whereas, the positive rate of allergic rhinitis caused by dust mite, fungus and canine epidermis was relatively low. CONCLUSION: The main allergens of the allergic rhinitis in Changji district are Chenopodium and Lupulus, similar as the dust mite. The allergen prick test, which is characterized as accuracy, sensitiveness and fastness, is an essential way to seek and screen those allergens. Thus, it can provide scientific instruction to the prevention of the allergic rhinitis in Changji district. PMID- 22070074 TI - [Kinetic expression of T-bet and GATA-3 genes in rat allergic rhinitis models]. AB - OBJECTIVE: To investigate kinetic expression of genes T-bet and GATA-3 in blood mononuclear cells (BMCs) in allergic rhinitis rats model at different stages of development of allergic rhinitis. METHOD: Twenty SD rats (including 10 male and 10 female) were divided into 2 groups, experimental group and control group, randomly, 10 rats for each group. Ten rats in experimental group were sensitized and intranasally challenged by OVA, aluminium hydroxide hydrate gel and Bordelella pertussis inactive microorganism suspension (B. pertussis) adjuvants, as allergic rhinitis models, Ten rats in control group were investigated using physiological saline only. BMCs were separated from 2 ml blood which was extracted from rat heart at the end of sensitization, 10- hour after the first challenge and 10-hour after the final challenge, respectively. RT-PCR was utilized to detect the expression of T-bet and GATA-3. RESULT: At the end of sensitization, 10-hour after the first challenge and 10-hour after the final challenge, in experimental group, Relative quantitation of expression of T-bet was 0.404 +/- 0.187, 1.676 +/- 0.708, 0.503 +/- 0.514 and that of GATA-3 was 0.434 +/- 0.147, 0.600 +/- 0.480, 1.029 +/- 0.690, respectively. While, In control group, Relative quantitation of expression of T-bet was 0.487 +/- 0.212, 0.486 +/- 0.148, 0.495 +/- 0.103 and and its of GATA-3 was 0.596 +/- 0.249, 0.474 +/- 0.101, 0.550 +/- 0.119, respectively. At 10-hour after the first challenge, relative quantitation of expression of T-bet in experimental group was increased markedly and there was significant difference compared with contol group (t=4.18, P<0.01). In experimental group, The amount of expression of T-bet at 10-hour after first challenge was higher than it at 10-hour after the final challenge and there was markedly difference (t=5.14, P<0.01). The amount of expression of T-bet at 10-hour after first challenge was increased significantly compared with it at the end of sensitization (t= 5.27, P<0.01). while, the expression of GATA-3 at 10 hour after final challenge was markedly increased compared with it at the end of sensitization (t= 3.51, P<0.05) and was higher than it at 10-hour after first challenge (t=2.53, P<0.05). At 10-hour after final challenge, The amount of expression of GATA-3 in experimental group was significantly higher than it in control group (t=2.71, P<0.05). However, both the expression of GATA-3 and T-bet had not markedly changed in control group. CONCLUSION: It is thought that the development of allergic rhinitis is a successive and sequencing kinetic course, and imbalance of expression of GATA-3 and T-bet may be genetic base on allergic rhinitis, both GATA-3 and T-bet were involved in allergic rhinitis only in different phase of development of allergic rhinitis. PMID- 22070076 TI - [Individual management of Meniere's disease and evaluation of functional outcome]. AB - OBJECTIVE: To investigate individual management for Meniere's disease and analyze outcomes of nonsurgical and surgical management of Meniere's disease. METHOD: Patients with Meniere's disease were staged according to hearing and quality of life. The individual management according to the staging was established, including outpatient treatment (lifestyle change, medical management and intratympanic steroids), endolymphatic sac decompression or drainage, vestibular neurectomy and labyrinthectomy. The characteristics of patients who underwent surgical management were analyzed. The functional outcomes of surgery in dizziness, hearing loss and quality of life were evaluated for 12-month postoperative follow-up. RESULT: Twenty patients underwent intratympanic injection of dexamethasone. Dizziness improved in 70% (14/20), tinnitus improved in 41% (7/17), and aural fullness improved in 36% (4/11). There were 55 patients who underwent surgical managements for 57 times. Endolymphatic sac decompression or drainage was carried out in 27 patients for 28 times, vestibular neurectomy in 26 patients and labyrinthectomy in 3 patients. Vertigo control rate was 75% in patients with endolymphatic sac decompression or drainage, 100% in vestibular neurectomy and 100% in labyrinthectomy at 12-month postoperative follow-up. CONCLUSION: The non-surgical management and endolymphatic sac decompression or drainage can improve vertigo and ameliorate quality of life. Vestibular neurectomy and labyrinthectomy are effective surgical managements to eliminate vertigo. The management of Meniere's disease depends on several factors: stages of vertigo and hearing, quality of life, surgical contraindications and subjective desire. Therefore, the management for Menieres disease must be individualized for each patient. PMID- 22070075 TI - [Comparative study of three primary culture methods of human epithelial cells of nasal polyps in vitro]. AB - OBJECTIVE: To compare three primary culture methods of human epithelial cells of nasal polyps in vitro, and explore a suitable method to be used in further study. METHOD: Shape and appearance of human epithelial cells of nasal polyps were observed, and success ratio and growth curve of primarily cultural were achieved by enzymatic dissociation, isolated cell ABC culture and tissue piece culture method respectively. RESULT: By comparing achievement ratios, the isolated cell ABC culture method (87.5%) was shown to be superior to enzymatic dissociation (78.13%) and tissue piece culture methods (83.33%), but no statistical significance was found (P>0.05). The growth curves of two isolated cell culture methods were higher than that of tissue piece culture. CONCLUSION: The isolated cell ABC culture model is more suitable for primary culture due to its faster proliferation, less promiscuity, and more stable and reliable cell supply for nasal polyps research. PMID- 22070077 TI - [Study of hearing loss in 200 patients with subjective tinnitus]. AB - OBJECTIVE: To analyze the hearing loss profiles in patients with tinnitus, and then provide clinical foundation for further studying the etiology and examination methods of tinnitus. METHOD: Ear specialist examination, acoustic impedance test,normal frequency pure tone audiometry and extended high frequency audiometry were applied to 200 patients with chief complaint of subjective tinnitus. RESULT: Among the 200 tinnitus cases, 123 (61.5%) patients were diagnosed with unilateral tinnitus, 77 (38.5%) patients with bilateral tinnitus and 46 (23.0%) cases with normal hearing. In those patients with unilateral tinnitus, by comparing the hearing threshold of affected side and contralateral side (0.125-8 kHz), the difference was statistically significant (P < 0.05), but in extended high frequency (> 10 kHz), the difference between two groups was not statistically significant (P > 0.05). There was significant difference in hearing threshold between tinnitus patients with normal and abnormal hearing in normal frequency (P < 0.05), meantime the detection rate in abnormal hearing group was lower than the normal group. CONCLUSION: Tinnitus can occur in people with normal hearing. Early in tinnitus,further study need be undertaken on whether the audiometry extended high frequency can offer the early evidence of hearing loss for tinnitus patients or not. PMID- 22070078 TI - [A pre- and post-treatment study of quality of life in patients with benign paroxysmal positional vertigo]. AB - OBJECTIVE: To explore the effect of canalith repositioning procedure (CRP) on the quality of life (QOL) in patients with benign paroxysmal positional vertigo(BPPV). METHOD: The clinical data of 86 patients with BPPV (treatment group) and 120 normal ones (control group) were reviewed through the medical outcomes study short form (SF-36)and the dizziness handicap inventory (DHI), and the results of two groups were analyzed. RESULT: With SF-36 scales for evaluation of QOL, the results showed that the scores of treatment group before CRP were significantly lower than that of the control group (P < 0.05). While using of DHI scales in evaluation of the treatment group patients before CRP, the results were significantly higher than that of the control group (P < 0.05). After CRP for 3 months, not only with SF-36 scales but also with DHI scales, there were no significant difference between the two groups (P > 0.05). CONCLUSION: CRP may obviously improve the clinical symptom of BPPV patients. The SF-36 and DHI scales could reflect the change of BPPV patient's QOL. PMID- 22070079 TI - [Preliminary investigation of psychologic factors in 76 tinnitus patients]. AB - OBJECTIVE: To study the psychological aspects of tinnitus patients, to analyze the distribution of psychologic obstacle in tinnitus patients, and then to provide information for diagnosing and treating tinnitus clinically. METHOD: All patients were detected their frequency and loudness of tinnitus. Then they were evaluated by symptom checklist 90 (SCL-90), life satisfaction scale, Pittsburgh sleep quality index (PSQI) and tinnitus handicap inventory (THI). All data were analyzed with statistical software SPSS11.0. RESULT: (1)There was no straight line correlation between frequency, loudness of tinnitus and the patient's scores from SCL-90, life satisfaction rating scale (LSR), life satisfaction index A (LSIA), LSIB, PSQI, THI. (2) To 76 tinnitus patients, some factors of SCL-90 were higher than internal nom. Compared with internal nom, tinnitus patients' score of LSR, LSIA and LSIB were all lower than it. Many of tinnitus patients had sleep disorder, the ratio was higher than internal nom. (3) Grouping these patients, based on the score of THI. To THI four grade group and THI five grade group, their satisfaction of lives were lower, some factors of SCL-90 were higher than internal nom. To THI five grade group, the ratio about sleep disorder was higher than internal nom. CONCLUSION: There is no straight line correlation between frequency, loudness of tinnitus and the patient's scores from SCL-90, LSR, LSIA, LSIB, PSQ1, THI. Grouping based on the score of THI, the groups of THI four grade and THI five grade are approved that they have psychologic obstacle obviously, they should be paid close attention. PMID- 22070080 TI - [Clinical effectiveness of REZ-I cochlear implants in post-lingual deafened Chinese dialect speakers]. AB - OBJECTIVE: To investigate the improvement of severe-to-profound hearing-impaired adults received REZ-I cochlear implant and to give an analysis to some Chinese dialect speakers. METHOD: With standard assessment table and standard testing program, 48 post-lingual hearing-impaired adults were divided into Mandarin language group (41 cases) and dialect group (7 cases). All of them were tested and scored for their hearing and speech perception abilities after 90 days rehabilitation. Sound field audio-metrics were performed at the same time. Clinical effectiveness of each subject in the two groups were assessed according to criteria, and efficacy index were statistically analyzed. RESULT: The total effective rates were 100% in both groups after 90 days hearing and speech perception rehabilitation. The clinical effectiveness were equal and there was no statistic significant differences between the groups. CONCLUSION: REZ-I cochlear implantation has similar effect for Chinese dialect spoken adults compared to mandarin spoken adults with post-lingual severe-to-profound hearing loss via appropriate postoperative rehabilitation. PMID- 22070081 TI - [Clinical evaluation of acute low-tone sensorineural hearing loss]. AB - OBJECTIVE: To assess the effect of treatment on acute low-tone sensorineural hearing loss and the related factors on the prognosis. METHOD: A total of 398 inpatients with sudden deafness were retrospectively analyzed. Among them, 41 cases were diagnosed as acute low-tone hearing loss and then subjected to combined treatment with glucocorticoids. The relativity between patients' gender, disease duration and age of onset and curative effect were analyzed. RESULT: The acute low-tone sensorineural hearing loss accounted for 10.30% of sudden deafness. Among which, female cases were significantly more than men, accounting for 70.73% of the total. At the first diagnosis, the average hearing threshold of three low tones was (48.43 +/- 11.67) dB against (18.86 +/- 9.40) dB of three high tones. After treatment, those two values were (27.07 +/- 11. 52) dB and (17.60 +/- 9.15) dB, respectively. There was statistical difference between three low tones and three high tones before treatment (t = 15.42, P < 0.01). There was statistical difference for three low tones before and after treatment (t = 10.69, P < 0.01) while there was no difference for the high ones before and after treatment(t = 1.93, P > 0.05). No obvious difference of the cure rate and effectiveness was found between male and female patients (P > 0.05). The incidence of acute low-tone sensorineural hearing loss was high in the age range of 21-40 years, accounting for 68.29% of the total. The cure rates were statistically different between patients less than 40 years old and 41-60 years old (chi2 = 6.662, P < 0.05), but the effectiveness had no difference (P > 0.05). There was no difference of cure rate and effectiveness between those with duration less than or equal to 7 days and those with more than 7 days (P > 0.05). CONCLUSION: The combined therapy with glucocorticoids shows good effects on treating acute low-tone sensorineural hearing loss. Neither gender nor duration affect the prognosis. Age of onset is related to the prognosis. PMID- 22070082 TI - [Meta-analysis of the effects of radiotherapy and surgery on carcinoma of the middle ear]. AB - OBJECTIVE: To evaluate the effects of radiotherapy and surgery on carcinoma of the middle ear. METHOD: A review of five published literatures was conducted according to defined selection criteria by the Review Manager 5.0 statistical software. RESULT: There were no systematic reviews or large-scale RCTs between radiotherapy and symptomatic treatment containing surgery and radiotherapy for carcinoma of the middle ear. CONCLUSION: Radiotherapy and symptomatic treatment for carcinoma of the middle ear have no obvious differences. The radiotherapy is the first choice for the treatment of squamous cell carcinoma of the middle ear. PMID- 22070083 TI - [Tympanoplasty with soft-wall reconstruction of ear canal]. AB - OBJECTIVE: To observe the therapeutic effect of tympanoplasty with soft-wall reconstruction of ear canal for chronic otitis media with cholesteatoma. METHOD: Seventy-three patients (76 ears) suffering from chronic otitis media with cholesteatoma were treated with canal wall down mastoidectomy with tympanoplasty. Postauricular myo-periosteal flap was used to the soft-wall reconstruction of ear canal, and the cavityplasty of auricular concha was not performed. The auricular bone prosthesis was made of the autogeneic mastoid cortical bone or residual incus. The postoperative modality and the function of external auditory canal and the postoperative hearing and the postoperative complications were observed. RESULT: The mean dry ear time was (21.1 +/- 3. 1) days after surgery in this study. The postoperative modality of external auditory canal was normal on the whole. The patients were followed up between 6 months and 24 months after surgery. The postoperative average air conduction hearing was improved by (14.5 +/- 6.1) dB HL. CONCLUSION: Tympanoplasty with soft-wall reconstruction of ear canal using the postauricular myo-periosteal flap can recover the modality and function of external auditory canal on the whole, and the cavityplasty of auricular concha is not needed. The postoperative hearing can be improved by this technique satisfactorily. PMID- 22070085 TI - [The cloning and sequencing of SD rat Atoh1 gene CDS region]. AB - OBJECTIVE: To clone Atoh1 gene coding sequence of SD rat and construct the Eukaryotic expression plasmid pAtoh1-IRES2-EGFP,and to study its expression in 293T cells. METHOD: Total RNA was extracted from colon of SD rat. Atoh1 cDNA was obtained by RT-PCR amplification and subcloned into PMD-19T vector. The purified digested fragment was connected into Eukaryotic expression vector pIRES2-EGFP to construct the recombinant plasmid. The recombinant expression plasmid was identified by enzyme digestion and sequence analysis and then transfected into 293T cells with Lipofectamine. The expression of green fluorescent protein was detected through fluorescence microscope. RESULT: Compared cloned DNA sequence of Atoh1 gene CDS area with the reference sequences published in GeneBank, there were two base nonsense mutation in the sequence, deduced amino acid of cloning sequences as the same as reference sequences. Two bases should be single nucleotide polymorphism. Results of enzyme digestion and sequencing confirmed the successful construction of the recombinant plasmid. The expression of the green fluorescent protein was observed in the transfected 293T cells 24 h after transfection by fluorescence microscope. CONCLUSION: pIRES2-EGFP-Atoh1 can be constructed and expressed successfully in the 293T cells, which will guide further research on gene therapy for sensorineural hearing loss. PMID- 22070084 TI - [Aberrant promoter hypermethylation of CHFR in nasopharyngeal carcinoma]. AB - OBJECTIVE: To discover the relationship of transcriptional levels and promoter methylation status of CHFR gene in human nasopharyngeal carcinoma,to discuss the significance and epigenetic mechanism of CHFR inactivation in NPC, and to evaluate the feasibility of detecting methylated CHFR in nasopharyngeal swab as a means for diagnosis of NPC. METHOD: Transcriptional levels of CHFR was evaluated by RT-PCR. Methylation specific PCR was used to detect the methylation status of CHFR in NPC cells, normal nasopharyngeal epithelia, primary tumors and their paired nasopharyngeal swabs. Detailed methylation status was confirmed by bisulfite sequencing. NPC cells were treated by the methyltransferase inhibitor 5 aza-dC and the reactivation of CHFR was evaluated by RT-PCR. RESULT: CHFR transcription was inactivated in NPC. The methylation frequency in NPC primary tumors and their paired swabs were 65.5% and 63.8%, respectively, with a 86.2% concordance. Bisulfite sequencing revealed a dense methylation in NPC cells and primary tumors, but all the normal nasopharyngeal epithelia were unmethylated. CHFR expression were restored after 5-aza-dC treatment. CONCLUSION: CHFR is epigenetically inactivated by promoter methylation in NPC. Detecting methylated CHFR can be served as a useful non-invasive means for diagnosis of NPC. PMID- 22070086 TI - Using trace elements in particulate matter to identify the sources of semivolatile organic contaminants in air at an alpine site. AB - An approach using trace elements in particulate matter (PM) to identify the geographic sources of atmospherically transported semivolatile organic contaminants (SOCs) was investigated. Daily samples of PM and SOCs were collected with high-volume air samplers from 16 January to 16 February 2009 at Temple Basin, a remote alpine site in New Zealand's Southern Alps. The most commonly detected pesticides were dieldrin, trans-chlordane, endosulfan I, and chlorpyrifos. Polycyclic aromatic hydrocarbons and polychlorinated biphenyls were also detected. For each sampling day, the relative contribution of PM from regional New Zealand versus long-range Australian sources was determined using trace element profiles and a binary mixing model. The PM approach indicated that endosulfan I, indeno[1,2,3-c,d]pyrene, and benzo[g,h,i]perylene found at Temple Basin were largely of Australian origin. Local wind observations indicated that the chlorpyrifos found at Temple Basin primarily came from the Canterbury Plains in New Zealand. PMID- 22070087 TI - A native disulfide stabilizes non-native helical structures in partially folded states of equine beta-lactoglobulin. AB - Equine beta-lactoglobulin (ELG) assumes non-native helices during refolding and in partially folded states. Previously, circular dichroism (CD) combined with site-directed mutagenesis identified helical regions in the acid- and cold denatured states of ELG. It is also known that a fragment of ELG, CHIBL (residues 88-142), has a structure similar to that of the cold-denatured state. For the study reported herein, the structure of a shorter fragment, CHIBLDeltaF (residues 97-142), was investigated by CD and nuclear magnetic resonance spectroscopy. The secondary chemical shifts clearly showed that non-native alpha-helices are present in two different regions, residues 98-107 and 114-135, and are connected by a native disulfide bond. The CD spectra of two peptides that correspond to the helical regions are characterized by weak helical signatures, and the sum of their CD spectra is nearly the same as the spectrum of disulfide-reduced CHIBLDeltaF. Therefore, the non-native helices are stabilized by the disulfide, and non-native helix formation may occur only during the refolding of the disulfide-intact protein. Supporting this conclusion is the observation that tear lipocalin, a homologue of ELG that lacks the disulfide, does not form non-native helices during folding. PMID- 22070088 TI - Analysis of nonextractable phenolic compounds in foods: the current state of the art. AB - More than 500 phenolic compounds have been reported as present in foodstuffs, and their intake has been related to the prevention of several chronic diseases. Most of the literature on phenolic compounds focuses on those present in the supernatant of aqueous-organic extractions: extractable phenolics. Nevertheless, significant amounts of phenolic compounds remain in the solid residues after such extractions. These nonextractable phenolics are mostly proanthocyanidins, phenolic acids, and hydrolyzable tannins that are closely associated with the food matrix. Studies of this fraction of dietary phenolic compounds are scarce, and the few there are usually refer to particular types of phenolics rather than to the fraction as a whole. The present review reports the state-of-the-art methods that currently exist for analyzing nonextractable phenolic compounds in foods. PMID- 22070089 TI - Small molecular therapies for rheumatoid arthritis: where do we stand? AB - INTRODUCTION: Early aggressive treatment and utilization of targeted biological therapies for rheumatoid arthritis (RA) has dramatically improved patient outcomes. Even with this approach up to 50% of patients fail to achieve a significant clinical response and these therapies require subcutaneous injection or intravenous administration and are costly. Development of small molecules that can be administered orally has progressed and several are under investigation as potential treatments for RA. This manuscript will update the status of the small molecules under development. AREAS COVERED: This review summarizes the newer molecular protein kinase targets involved in signal transduction of inflammatory mediators and the development of inhibitors to these kinases. Additionally, the results of clinical trials evaluating these therapies will be reviewed. EXPERT OPINION: Based on the results of randomized clinical trials there is significant likelihood that a small molecular therapy to kinases involved in proinflammatory cytokine production will soon be available in the clinic. The benefit/risk profile is presently being determined in multiple late phase clinical trials. PMID- 22070090 TI - European veterinary dissertations. PMID- 22070091 TI - Theatrical entertainments and kind words: nursing the insane in Western North Carolina, 1882-1907. AB - This paper argues that at the turn of the 19th century, nurses at the State Hospital in Morganton, North Carolina (now called Broughton Hospital) played critical roles in successfully implementing the best-known therapeutic methods of the time. They were also instrumental in developing the hospital's visibility and acceptance in rural western North Carolina. When the Hospital established its first nurse training school in 1895, this corps of first-generation western North Carolinians practising institutional nursing was highly esteemed in their field. Their skills not only served the community outside of the Hospital's walls, but were also sought out by other private and state asylums. PMID- 22070094 TI - Appendiceal goblet cell metaplasia and benign obstructive mucus retention in children: report of eight cases and review of the literature. AB - We report the clinical-pathologic study of 8 cases of pediatric benign, postobstructive, appendiceal mucus retention in patients 3-15 years of age. The appendices showed very limited acute inflammation. Their most significant change consisted of minimal to mild dilatation of the distal lumen, which was filled with mucus and lined by an epithelium showing often dramatic increase in mucus cells devoid of atypia and without any of the villous proliferation reported in instances of "mucosal hyperplasia" observed in adult patients. In all 8 cases, there was seepage of mucus through the appendiceal wall into the surrounding tissue, eliciting a macrophagic reaction. Proximal to the zones of mucus retention, the lumen of 2 of the appendices was obstructed by a fecalith, and 2 exhibited fibrous obliteration of the lumen at that site. We believe the condition results from obstruction and focal inflammation, which isolate the distal portion of the appendix and elicit goblet cell metaplasia, the secretion of which is followed by luminal distention, eventual rupture, and seepage of mucus within the wall and the mesoappendix. The clinical and radiologic picture of this condition may be mistaken for that of an acute appendicitis complicated by rupture and abscess formation. The report provides an opportunity to describe and characterize "appendiceal mucosal goblet cell metaplasia," a seldom mentioned entity associated with benign appendiceal obstructive mucus retention in children. PMID- 22070093 TI - Overexpression of GCN2-type protein kinase in wheat has profound effects on free amino acid concentration and gene expression. AB - A key point of regulation of protein synthesis and amino acid homoeostasis in eukaryotes is the phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) by protein kinase general control nonderepressible (GCN)-2. In this study, a GCN2-type PCR product (TaGCN2) was amplified from wheat (Triticum aestivum) RNA, while a wheat eIF2alpha homologue was identified in wheat genome data and found to contain a conserved target site for phosphorylation by GCN2. TaGCN2 overexpression in transgenic wheat resulted in significant decreases in total free amino acid concentration in the grain, with free asparagine concentration in particular being much lower than in controls. There were significant increases in the expression of eIF2alpha and protein phosphatase PP2A, as well as a nitrate reductase gene and genes encoding phosphoserine phosphatase and dihydrodipicolinate synthase, while the expression of an asparagine synthetase (AS1) gene and genes encoding cystathionine gamma synthase and sulphur-deficiency-induced-1 all decreased significantly. Sulphur deficiency-induced activation of these genes occurred in wild-type plants but not in TaGCN2 overexpressing lines. Under sulphur deprivation, the expression of genes encoding aspartate kinase/homoserine dehydrogenase and 3-deoxy-D-arabino heptulosonate-7-phosphate synthase was also lower than in controls. The study demonstrates that TaGCN2 plays an important role in the regulation of genes encoding enzymes of amino acid biosynthesis in wheat and is the first to implicate GCN2-type protein kinases so clearly in sulphur signalling in any organism. It shows that manipulation of TaGCN2 gene expression could be used to reduce free asparagine accumulation in wheat grain and the risk of acrylamide formation in wheat products. PMID- 22070095 TI - Impact of alcohol habits and smoking on the risk of new-onset atrial fibrillation in hypertensive patients with ECG left ventricular hypertrophy: the LIFE study. AB - BACKGROUND: The incidence of new-onset atrial fibrillation (AF) is increased by uncontrolled hypertension, and antihypertensive treatment reduces new-onset AF. However, it is unclear whether alcohol intake and smoking influence the risk of new-onset AF during antihypertensive treatment. METHODS: In the Losartan Intervention For Endpoint reduction in Hypertension (LIFE) study, a double blinded, randomized, parallel-group study, 9193 hypertensive patients with electrocardiogram (ECG)-documented left ventricular hypertrophy (LVH), randomized to once-daily losartan- or atenolol-based antihypertensive therapy were followed for a mean of 4.8 years. At baseline, 8831 patients (54% women, mean age 67 years, mean blood pressure 174/98 mmHg after placebo run-in) had neither a history of AF nor AF on ECG, and they were thus at risk of developing this condition during the study. RESULTS: New-onset AF occurred in 353 (4%) patients. Univariate Cox analyses showed that intake of alcohol > 10 units/week compared with less or no alcohol intake predicted new-onset AF (Hazard ratio, HR = 1.60 [95% CI 1.02-2.51], p = 0.043). Multivariate Cox regression analysis showed that intake of alcohol > 10 units/week predicted new-onset AF (p = 0.010) independently of most other univariate predictors, except when also baseline serum cholesterol, serum potassium and urinary albumin/creatinine ratio were included in the model (HR = 1.60 [95% CI 0.94-2.72], p = 0.081). Impact of smoking was not significant in Cox univariate or multivariate analyses, and there were no significant interactions between high alcohol intake and either smoking or gender on the risk of getting AF. CONCLUSIONS: Up to 10 drinks of alcohol per week appears to be safe with respect to the risk for AF in hypertensive patients with LVH. Our data suggest that alcohol intake above this level may be marginally deleterious, while no effect of smoking on risk of AF was detected in hypertensive patients with LVH. PMID- 22070097 TI - Consensus on equine tendon disease: building on the 2007 Havemeyer symposium. PMID- 22070096 TI - Intercepting Wacker intermediates with arenes: C-H functionalization and dearomatization. AB - An intramolecular cyclization cascade reaction has been developed utilizing a high valent palladium intermediate that generates a carbon-carbon and carbon oxygen bond in a single transformation. This method provides rapid access to highly functionalized tricyclic scaffolds, including spirocyclic cyclohexadienones. Good yields and mild conditions are reported with high tolerance toward oxygen and water. PMID- 22070098 TI - Contribution of "modified genetic sonography" to the combined test as a screening method for chromosomal abnormalities. AB - OBJECTIVES: We propose to assess the contribution of "modified genetic sonography" (MGS) to the combined test (CT) as a method of stepwise sequential screening (1st step: CT, 2nd step: MGS) for chromosome abnormalities in the general population of pregnant women. METHODS: Prospective study. During a 4 year study period (July 2005-June 2009) 16,548 pregnancies underwent a CT combined with MGS (major malformation and nuchal fold) as a screening method for chromosome abnormalities. We assessed sensitivity and false positive rate (FPR) (95% CI). RESULTS: We offered a chromosome abnormalities screening test to 96.6% of pregnancies (15,995 cases). 14,160 cases are analyzed (1st step: CT, 2nd step: MGS) including 49 chromosome abnormalities and 35 Down's syndrome (DS). The sensitivity of CT for DS was 77.1% [95% CI, 63.2-91] (27/35) and 77.5% for all chromosome abnormalities [95% CI, 65.8-89.2] (38/49) with a FPR of 4.4% [95% CI, 4.1-4.7]. If MGS was combined with CT, the sensitivity for DS was 91.4% [95% CI, 82.1-99] (32/35) and 93.8% for all chromosome abnormalities [95% CI, 87-99] (46/49) for a FPR of 5.1% [95% CI, 4.7-5.5]. CONCLUSIONS: The addition of an MGS to combined first-trimester screening test for aneuploidy improved sensitivity by 14.3% while only increasing the FPR by 0.7%. PMID- 22070099 TI - Cytochrome c-mediated formation of S-nitrosothiol in cells. AB - S-nitrosothiols are products of nitric oxide (NO) metabolism that have been implicated in a plethora of signalling processes. However, mechanisms of S nitrosothiol formation in biological systems are uncertain, and no efficient protein-mediated process has been identified. Recently, we observed that ferric cytochrome c can promote S-nitrosoglutathione formation from NO and glutathione by acting as an electron acceptor under anaerobic conditions. In the present study, we show that this mechanism is also robust under oxygenated conditions, that cytochrome c can promote protein S-nitrosation via a transnitrosation reaction and that cell lysate depleted of cytochrome c exhibits a lower capacity to synthesize S-nitrosothiols. Importantly, we also demonstrate that this mechanism is functional in living cells. Lower S-nitrosothiol synthesis activity, from donor and nitric oxide synthase-generated NO, was found in cytochrome c deficient mouse embryonic cells as compared with wild-type controls. Taken together, these data point to cytochrome c as a biological mediator of protein S nitrosation in cells. This is the most efficient and concerted mechanism of S nitrosothiol formation reported so far. PMID- 22070100 TI - Cigarette smoke increases TLR4 and TLR9 expression and induces cytokine production from CD8(+) T cells in chronic obstructive pulmonary disease. AB - BACKGROUND: Cigarette smoke is a major risk factor for chronic obstructive pulmonary disease (COPD), an inflammatory lung disorder. COPD is characterized by an increase in CD8(+) T cells within the central and peripheral airways. We hypothesized that the CD8(+) T cells in COPD patients have increased Toll-like receptor (TLR) expression compared to control subjects due to the exposure of cigarette smoke in the airways. METHODS: Endobronchial biopsies and peripheral blood were obtained from COPD patients and control subjects. TLR4 and TLR9 expression was assessed by immunostaining of lung tissue and flow cytometry of the peripheral blood. CD8(+) T cells isolated from peripheral blood were treated with or without cigarette smoke condensate (CSC) as well as TLR4 and TLR9 inhibitors. PCR and western blotting were used to determine TLR4 and TLR9 expression, while cytokine secretion from these cells was detected using electrochemiluminescence technology. RESULTS: No difference was observed in the overall expression of TLR4 and TLR9 in the lung tissue and peripheral blood of COPD patients compared to control subjects. However, COPD patients had increased TLR4 and TLR9 expression on lung CD8(+) T cells. Exposure of CD8(+) T cells to CSC resulted in an increase of TLR4 and TLR9 protein expression. CSC exposure also caused the activation of CD8(+) T cells, resulting in the production of IL 1beta, IL-6, IL-10, IL-12p70, TNFalpha and IFNgamma. Furthermore, inhibition of TLR4 or TLR9 significantly attenuated the production of TNFalpha and IL-10. CONCLUSIONS: Our results demonstrate increased expression of TLR4 and TLR9 on lung CD8(+) T cells in COPD. CD8(+) T cells exposed to CSC increased TLR4 and TLR9 levels and increased cytokine production. These results provide a new perspective on the role of CD8(+) T cells in COPD. PMID- 22070101 TI - In-house information about and contact with self-help groups in breast cancer patients: associated with patient and hospital characteristics? AB - The number of breast cancer patients who are informed about and have contact with patient self-help groups (SHGs) during their hospital stay varies across hospitals. The aim of this study is to investigate which patient and hospital characteristics contribute to these differences. Multilevel regression analysis was applied, using data on hospital characteristics and data from a patient survey, which catalogued the disease and socio-demographic characteristics of newly diagnosed breast cancer patients, and recorded if they were informed about and had contact with SHGs during their hospital stay. Data from 2639 patients from 82 hospitals were analysed. The odds of being informed about SHGs were significantly lower if patients were treated at a teaching hospital. Patients aged 40 to 59 years significantly more often reported that they were informed about SHGs than patients aged 60 to 69 years. Patients with the highest education certificates significantly more often reported that they both were informed about and have had contact with SHGs. These results suggest that in teaching hospitals, information provided to patients about SHGs is reduced. Furthermore, patients are differentially given information about SHGs and have different levels of contact with SHGs, based on their age and education. PMID- 22070103 TI - Errata. PMID- 22070104 TI - Preface. PMID- 22070102 TI - Clients with intellectual disabilities on psychiatric units: care coordination for positive outcomes. AB - The transition from residential facilities to and from the psychiatric hospital setting is difficult for individuals with intellectual disabilities (ID). In the U.S.A., specialized psychiatric units for individuals with ID are uncommon and this population is usually served in generalized services. Nevertheless, providers of mental health services in the U.S.A. receive little training in their specific needs. Best practices call for coordination of plans between psychiatric units and community agencies, multidisciplinary care plans, staff education and comprehensive discharge planning in order to improve outcomes of psychiatric hospitalization. An inner city psychiatric unit in a major academic medical centre and a community agency providing residential care for individuals with ID cooperated to provide a plan of care for a client with ID both for hospitalization and for discharge leading to improved outcomes. PMID- 22070105 TI - Population policy: Personal notes. AB - Abstract These are the population years: throughout the world, in both developing and developed countries, there has been a growing debate on population policy. In this paper population policy refers to governmental actions that are designed to alter population events, or that do alter them. The concern with policy seems to center in the relationships between four demographic variables (size, rates, distribution, composition) and four 'quality of life' categories as both determinants and consequences (comprehended here as economic, political, ecological/environmental, social). As to policy means, they can be seen as being five in number (information, voluntary programmes, change in social institutions, incentives and disincentives, and coercion) with the potential of affecting the three factors of fertility, mortality, and migration. The relationships and effects of these conceptual cross tabulations are illustrated. PMID- 22070106 TI - Latin American population prospects in the next fifteen years. AB - Abstract This paper discusses some of the results of population projections by age and sex for the period 1965-85 which were prepared some years ago for Latin American countries. Despite the limitation of the data there are several short range implications which deserve attention. The area which had the highest rate of growth among all the major areas of the world during the last 50 years, is expected to maintain a stable rate during the next 15 years. Though some fertility decline is anticipated, it is bound to be slower, in general, than expected in East and South Asia where cultural factors are not as strong. The gain in mortality is also expected to be relatively slow, but this is only because mortality has already reached fairly low levels compared to Asia and Africa. However, because of the young age distribution, the area is expected to have in the near future crude death rates which are so low that they have probably not been experienced before in normal human populations. A simple grouping of the population into pertinent age-sex groups gives information which undoubtedly raises serious questions concerning the adequacy of the measures which are now being taken or planned to meet the various needs of different population categories. For instance, in addition to existing problems, the economies will have to face the problem of absorbing within the next 15 years the anticipated increases of about 84 million in the labour force, the educational systems will have to provide for the schooling of about 28 million additional children of school age, and the planners for social and economic development will have to consider the measures necessary to face an increase of about 56% in the number of females of reproductive ages. The figures show clearly that the problems have different dimensions in different regions, with those of Central America being perhaps particularly serious. PMID- 22070107 TI - Age patterns of marriage. AB - Abstract In different populations there is a common curve describing first marriage frequency (first marriages per woman) as a function of age for each cohort. To fit the variety of patterns of human nuptiality it suffices to choose the age that serves as origin for a standard curve of first-marriage frequency, and to choose appropriate horizontal and vertical scales for the curve. The prevalence of a standard form for first-marriage frequency implies that the proportion ever-married in any cohort also rises along a standard curve, subject to choice of origin (the earliest age of first marriage), vertical scale (the proportion ever-marrying by the end of life), and horizontal scale (the pace at which the proportion ever-married increases with age). A mathematical expression (a double exponential) is found to fit the risk offirst marriage (among those who ever marry), and some of the implications of uniform features of nuptiality in different populations are discussed. PMID- 22070108 TI - Explaining cross-cultural variations in age at marriage and proportions never marrying. AB - Abstract According to censuses taken around 1960, the distinction between the 'European' pattern of late marriage and high proportions never married and the 'traditional' pattern of early and universal marriage remains generally valid for female populations in spite of trends toward convergence in the past few decades. Among male populations, however, the regional overlap is great. Variations in the timing and quantity of nuptiality in 57 countries in Europe, the Middle East, Asia and the English-speaking nations overseas are explained on the basis of variables measuring the desirability and feasibility of marriage. The conclusion is that marriage is becoming more feasible in the wealthier nations of the West and less feasible in many developing non-Western nations. Social and economic penalties of non-marriage are stronger in non-Western societies than in the West, and stronger for women than for men. PMID- 22070109 TI - Stable, semi-stable populations and growth potential. AB - Abstract Starting from the definition of a Malthusian population given by Alfred J. Lotka, the author recalls how the concept of stable population is introduced in demography, first as a particular case of stable populations, and secondly as a limit of a demographic evolutionary process in which female age specific fertility rates and age-specific mortality rates remain constant. Then he defines a new concept: the semi-stable population which is a population with a constant age distribution. He shows that such a population coincides at any point of time with the stable population corresponding to the mortality and the fertility at this point of time. In the remaining part of the paper it is shown how the concept of a stable population can be used for defining a coefficient of inertia which measures the resistance of a population to modification of its course as a consequence of changing fertility and mortality. Some formulae are established to calculate this coefficient first for an arbitrary population, and secondly for a semistable population. In this second case the formula is particularly simple. It appears as a product of three terms: the expectation of life at birth in years, the crude birth rate, and a coefficient depending on the rate of growth and for which a numerical table is easy to establish. PMID- 22070110 TI - The economic explanation of fertility changes in the United States. AB - Abstract It is widely assumed that fertility varies positively with economic conditions. Actually this assumption receives little support from the historical record. For a century before 1930 fertility declined while the economy expanded and real incomes rose. Then for nearly three decades fertility and incomes fell and rose together. Since 1960 they have again moved in opposite directions. Clearly, no simple generalization about their relation will hold water. More sophisticated explanations are based on relative rather than absolute incomes. Banks suggested that the downturn in English fertility in the 1870's might have occurred because standards of middle-class consumption rose faster than middle class incomes, but he found the evidence inconclusive. To reconcile the post war baby boom in the United States with earlier experience, Easterlin has argued that fertility is determined by the relationship between the income of couples in their twenties and the income of their parents ten to fifteen years earlier. Among the weaknesses of this theory as applied to U.S. experience are its failure to explain the sharp drop in fertility, including that of native white urban women, in the 1920's; the fact that fertility rose most in the baby boom at the higher socio-economic levels where incomes rose least; and the sharp decline of fertility after 1962 in spite of the favourable trend of incomes, including those of younger people. The broad conclusion is that while couples no doubt do consider income, employment opportunities, etc. in deciding how many children to have, such considerations have had a relatively minor influence on changes in fertility, which for the most part have been the result of changes in attitudes. Even the post-war baby boom was a result not only of higher incomes and full employment but also of a shift in attitudes toward family size, particularly among the better-educated, economically better-off sections of society. PMID- 22070111 TI - A comparison between current Indian fertility and late nineteenth-century Swedish and Finnish fertility. AB - Abstract The paper aims to probe causes of the current high level of the crude birth rate in India. This is accomplished by comparing the current Indian fertility level with that of Sweden and Finland during the last quarter of the nineteenth century. By utilizing marital distribution, age distribution and age specific marital fertility rates of the three countries, the basic demographic causes of high fertility in India can be established. In the second part, the factors causing age-specific marital fertility rates in India to be lower than nineteenth-century Sweden and Finland are discussed. This is done by comparing the levels of the followingsix variables, operating within marriage, between Indian and Scandinavian cultures: (1) Abstinence - voluntary and involuntary, (2) Frequency of coitus, (3) Incidence of sterility - primary and secondary, (4) Contraception and sterilization, (5) Incidence of foetal mortality and (6) Incidence of induced abortions. PMID- 22070112 TI - The structure of mortality during catastrophic years in a pre-industrial society. AB - Abstract The aim of the study is to examine the way in which the pattern of mortality in a pre-industrial society differed in catastrophic years from that in 'normal' years. Five Finnish parishes with a total population of 21,000 in 1850 were examined. The deaths were classified by season, age and cause. The results support the theory that epidemics not directly connected with starvation were the main causes of mortality peaks. PMID- 22070113 TI - An experiment with census-type age enumeration in Nigeria. AB - Abstract Censuses were held and data subsequently published in Nigeria in 1952/3 and 1963. Age data and other aspects of the enumerations gave rise to considerable doubts. In 1969 the Demographic Training and Research Unit of the University of Ife carried out a census of ages amongst 10,000 persons in the Western State of Nigeria employing in succession orthodox methods, supporting historical records, and two approaches involving the identification of single year cohorts of contemporaries. Certain other data were also collected for explanatory purposes. The project confirmedthe tendency for age misstatement to exaggerate the number of females aged 20-44 and the number of older males, and to understate the number of persons aged 0-9 and females aged 50-59. It was shown that amongst females, aged 15-24, there is a significant tendency for the ages of the unmarried to be understated and those of the married, expecially those of higher parity, to be overstated. Such tendencies may be reduced by any type of enumeration if more time and care is allowed but anomalously this may increase the underenumeration of the very young. The more elaborate methods of enumeration are examinedto see whether they yield more accurate data and whether their use would be possible in a national census. Age statement was examined in some detail and it was shown that the majority of data originate neither with respondents nor enumerators but with third parties, who may wellbe continuing and untrainable sources of biassed error. The project provided more evidence than anticipated on the validity of the 1963 Census in the area, thus leaving the relative validity of the 1952/3 and 1963 censuses and hence the likely population of Nigeria still an open question. PMID- 22070114 TI - Some problems in determining the number of acceptors needed in a family planning programme to achieve a specified reduction in the birth rate. AB - Abstract The paper attempts to revive professional interest in a problem originally considered by Lee and Isbister and which has assumed added importance recently because of the increasing number of national family planning programmes that are being instituted, which require the determination of the number of acceptors needed in a family planning programme in order to achieve a specified reduction in the birth rate. The publication of subsequent papers on births averted by programmes, notably by Potter and Wolfers, each of whom had made some criticisms of the paper by Lee and Isbister, has tended to obscure the differences in the nature between the problem raised by Lee and Isbister, and that discussedby Potter or Wolfers. The paper tries to bring out these differences and points out one of the limitations of the estimates of births averted obtained by using either Potter's or Wolfers's methods, viz. the inability to determine the time period to which the birth reduction refers, thereby further complicating the issues involved in assessing the social and economic implications of births averted by a family planning programme. The paper also points out some of the unrecognizedtechnical considerations which arise in dealingwith the 'target-setting' problem raised by Lee and Isbister and suggeststhat stochasticmodel studies might offera clue for evolving practical methods for tackling this problem. PMID- 22070115 TI - Fecundability and coital frequency. AB - Abstract The analysis previouslyreported (Population Studies, 23, 1969) of the risk of conceptionon different days of the menstrual cycleis extended so as to take someaccount of the agesof wives. The risks are estimated from data (basal body temperatures and occurrences of coitus) recorded by 241 married couples not using any contraceptives, to whom at least one child had previously been born. A mathematical formula relating natural fecundability to coital frequency is proposed and considered. PMID- 22070116 TI - Birth variations in populations which practise family planning. AB - Abstract In the first section it is demonstrated that permanent periodicities may appear in populations, in which fertility occurs at two or more ages, separated by ages, in which there is no fertility at all. It is also shown that where periodicity does disappear, this may take much longer than is usually assumed, before the stable age distribution is attained. The last section of the paper is based on Swedish data relating to female fertility for single-year cohorts and for periods. It is demonstrated that fertility behaviour of cohorts from different decades has varied considerably, not least as regards birth timing. This explains why the period fertility rate has varied in such an irregular fashion, whereas the rate for cohorts has moved much more regularly; after the original decline to an all-time low for the cohorts born around 1905, there has been a slow, and on the whole, regular increase. This increase is largely explained by a rise in nuptiality. If the total fertility rate required for reproduction is computed, it is seen that no cohorts born after about 1885 have reproduced themselves, and that for the cohorts born between 1895 and 1920 the gap was considerable. PMID- 22070120 TI - Conference of the World Society of Arrhythmias Athens, December 2011. PMID- 22070117 TI - The incidence of illegal abortion. AB - Abstract Previous estimates of the incidence of illegal abortion in this country are reviewed. It is suggested that data examined by Goodhart imply that there were more (perhaps many more) than 60,000 illegal abortions in 1967. Estimates of the incidence of female sterilizing operations are reviewed. It is suggested that in this country each female sterilizing operation averts about one live birth or - where induced abortion is the alternative - one induced abortion. PMID- 22070122 TI - Pattern of moderate-to-severe symptoms of premenstrual syndrome in a selected hospital in China. AB - AIM: Premenstrual syndrome (PMS) is a commonly encountered complaint among women. It may affect women's quality of life and reduce their occupational productivity. This study aims to describe the symptoms of moderate-to-severe PMS and to examine the onset, stability, and severity of PMS among Chinese women. METHODS: A descriptive study included 142 women with self-reported PMS, aged 18-45 years, who were recruited by the Outpatient Department of Gynecological Endocrinology, Peking Union Medical College Hospital. Premenstrual symptoms were retrospectively assessed by using screening questionnaires modified with the DSM-IV. In total, 126 eligible subjects were asked to record their daily symptoms during two consecutive menstrual cycles by using a premenstrual syndrome diary (PMSD). RESULTS: Of 126 eligible subjects, 67 filled in the PMSD for two cycles. The median of total scores of PMSD peaked on the day before menses and dropped after the beginning of the menses. Mood swings were the most common moderate-to-severe symptom prospectively reported by the subjects. The symptoms of PMS were relatively consistent across the two cycles. CONCLUSIONS: Women with moderate-to severe PMS were vulnerable to psychological symptoms. Further studies are needed to understand the correlations between hormonal changes and the experience of symptoms related to the menstrual cycle. PMID- 22070123 TI - Long non-coding RNAs in nuclear bodies. AB - High-throughput analyses of mammalian transcriptomes have revealed that more than half of the transcripts produced by RNA polymerase II are non-protein-coding. One class of these non-coding transcripts is the long non-coding RNAs (lncRNAs), which are more than 200 nucleotides in length and are molecularly indistinguishable from other protein-coding mRNAs. Although the molecular functions of these lncRNAs have long remained unknown, emerging evidence implicates the functional involvement of lncRNAs in the regulation of gene expression through the modification of chromatin, maintenance of subnuclear structures, transport of specific mRNAs, and control of pre-mRNA splicing. Here, we discuss the functions of a distinct group of vertebrate-specific lncRNAs, NEAT1/MENepsilon/beta/VINC, MALAT1/NEAT2, and Gomafu/RNCR2/MIAT, which accumulate abundantly within the nucleus as RNA components of specific nuclear bodies. PMID- 22070124 TI - Decreased methylation of the NK3 receptor coding gene (TACR3) after cocaine induced place preference in marmoset monkeys. AB - Epigenetic processes have been implicated in neuronal plasticity following repeated cocaine application. Here we measured DNA methylation at promoter CpG sites of the dopamine transporter (DAT1) and serotonin transporter (SERT) and neurokinin3-receptor (NK3-R)-receptor (TACR3) coding genes in marmoset monkeys after repeated cocaine injections in a conditioned place preference paradigm. We found a decrease in DNA methylation at a specific CpG site in TACR3, but not DAT1 or SERT. Thus, TACR3 is a locus for DNA methylation changes in response to repeated cocaine administration and its establishment as a reinforcer, in support of other evidence implicating the NK3-R in reinforcement- and addiction-related processes. PMID- 22070125 TI - Addressing non-adherence to antipsychotic medication: a harm-reduction approach. AB - This paper discusses the evidence base for interventions addressing non-adherence to prescribed antipsychotics. A case study approach is used, and the extent to which adherence improvement interventions might be used in collaboration with a specific patient is considered. The principles and application of harm-reduction philosophy in mental health are presented in a planned non-adherence harm reduction intervention. This intervention aims to acknowledge the patient's ability to choose and learn from experience and to reduce the potential harm of antipsychotic withdrawal. The intervention evaluation method is outlined. PMID- 22070126 TI - Retrobulbar primitive neuroectodermal tumor in a squirrel monkey (Saimiri sciureus). AB - BACKGROUND: A 2.8-year-old female captive-bred common squirrel monkey (Saimiri sciureus) showed exophthalmos of the right eye, and the eye was surgically enucleated. A tumor mass was found in the eye. METHODS: Formalin-fixed tumor samples were examined histopathologically and immunohistochemically for diagnosis. RESULTS: The retrobulbar tumor mass adhered to the sclera and infiltrated the choroid. Histopathologically, tumor cells were pleomorphic, arranged in a sheet pattern, and mimicked primitive neuroectodermal cells. The tumor cells were strongly positive for precursor neuronal cell markers (beta III tubulin, neuron-specific enolase, vimentin, nestin, doublecortin, oligo2, and S 100), but negative for mature cell markers (cytokeratin, neurofilament, and glial fibrillary acidic protein) and a retinoblastoma marker (rhodopsin). CONCLUSIONS: This is the first reported case for the retrobulbar location of primitive neuroectodermal tumor in non-human primates. PMID- 22070127 TI - Positively charged lanthanide complexes with cyclen-based ligands: synthesis, solid-state and solution structure, and fluoride interaction. AB - The syntheses of a new cyclen-based ligand L(2) containing four N-[2-(2 hydroxyethoxy)ethyl]acetamide pendant arms and of its lanthanide(III) complexes [LnL(2)(H(2)O)]Cl(3) (Ln = La, Eu, Tb, Yb, or Lu) are reported, together with a comparison with some Ln(III) complexes of a previously reported analogue L(1) in which two opposite amide arms have been replaced by coordinating pyridyl units. The structure and dynamics of the La(III), Lu(III), and Yb(III) complexes in solution were studied by using multinuclear NMR investigations and density functional theory calculations. Luminescence lifetime measurements in H(2)O and D(2)O solutions of the [Ln(L(2))(H(2)O)](3+) complexes (Ln = Eu or Tb) were used to investigate the number of H(2)O molecules coordinated to the metal ion, pointing to the presence of an inner-sphere H(2)O molecule in a buffered aqueous solution. Fluoride binding to the latter complexes was investigated using a combination of absorption spectroscopy and steady-state and time-resolved luminescence spectroscopy, pointing to a surprisingly weak interaction in the case of L(2) (log K = 1.4 +/- 0.1). In contrast to the results in solution, the X ray crystal structure of the lanthanide complex showed the ninth coordination position occupied by a chloride anion. In the case of L(1), the X-ray structure of the [(EuL(1))(2)F] complex features a bridging fluoride donor with an uncommon linear Eu-F-Eu entity connecting two almost identical [Eu(L(1))](3+) units. Encapsulation of the F(-) anion within the two complexes is assisted by pi-pi stacking between the pyridyl rings of two complexes and C-H...F hydrogen-bonding interactions involving the anion and the pyridyl units. PMID- 22070128 TI - Characterization of composite phthalocyanine-fatty acid films from the air/water interface to solid supports. AB - A commercial vanadyl 2,9,16,23-tetraphenoxy-29H,31H-phthalocyanine (VOPc) was dissolved in chloroform and spread on ultrapure water subphase in a Langmuir trough. The floating film was thoroughly characterized at the air-water interface by means of the Langmuir isotherm, Brewster angle microscopy, UV-vis reflection spectroscopy, and infrared measurements carried out directly at the air-water interface. All the results showed the formation of a non-uniform and aggregated floating layer, too rigid to be transferred by the Langmuir-Blodgett (LB) method. For this reason, a mixture of arachidic acid and VOPc was realized, characterized, and transferred by the LB technique on solid substrates. Interface measurements and atomic force microscopy analysis suggested the formation of a uniform arachidic acid film and a superimposed VOPc placed in prone configuration. PMID- 22070130 TI - Compression of cross-linked poly(vinylidene fluoride-co-trifluoro ethylene) films for facile ferroelectric polarization. AB - In this study, we demonstrated a facile route for enhancing the ferroelectric polarization of a chemically cross-linked poly(vinylidene fluoride-co-trifluoro ethylene) (PVDF-TrFE) film. Our method is based on thermally induced cross linking of a PVDF-TrFE film with a 2,2,4-trimethyl-1,6-hexanediamine (THDA) agent under compression. The remanent polarization (P(r)) of a metal/ferroelectric/metal capacitor containing a cross-linked PVDF-TrFE film increased with pressure up to a certain value, whereas no change in the P(r) value was observed in the absence of THDA. A film cross-linked with 10 wt % THDA with respect to PVDF-TrFE under a pressure of 100 kPa exhibited a P(r) of approximately 5.61 MUC/cm(2), which is 1.6 times higher than that in the absence of pressure. The enhanced ferroelectric polarization was attributed to highly ordered 20-nm-thick edge-on crystalline lamellae whose c-axes are aligned parallel to the substrate. The lamellae were effective for ferroelectric switching of the PVDF-TrFE when a cross-linked film was recrystallized under pressure. Furthermore, compression of a PVDF-TrFE film with a topographically prepatterned poly(dimethyl siloxane) mold gave rise to a chemically cross-linked micropattern in which edge-on crystalline lamellae were globally oriented over a very large area. PMID- 22070129 TI - A pilot study on the effect of short-term consumption of a polyphenol rich drink on biomarkers of coronary artery disease defined by urinary proteomics. AB - Polyphenol rich diets have been associated with a reduced risk of cardiovascular disease. We examined the effect of a polyphenol rich (P-R) drink on biomarkers assessed by urinary proteomics. Thirty nine middle aged and overweight subjects were randomized to P-R drink (n = 20) or placebo (n = 19) in addition to their normal diet. After two weeks urine samples were obtained for assessment of the urinary proteome using capillary electrophoresis coupled to a mass spectrometer. A total of 93 polypeptides were found to be candidates for differential distribution with a nominal p-value <0.05, though these differences did not reach significance when multiple testing was accounted for. Sequences were determined in 19 of these demonstrating that they originate from alpha-1 antitrypsin, collagens, fibrinogen alpha and IgG kappa. Levels of 27 polypeptides were greater than 4-fold different between the two groups. Of these, 7 were previously found to be part of a coronary artery disease (CAD) specific urinary biomarker pattern. Their direction of expression was closer to the healthy state in the P-R drink group and closer to CAD state in the placebo group. Our data suggest that the P-R drink may have beneficial effects on urinary biomarkers of CAD. The data encourage the planning of future prospective studies, aimed at investigating significant effects of polyphenol rich dietary products. PMID- 22070132 TI - Erratum. PMID- 22070131 TI - Cytochrome P450 polymorphisms and drug-induced interstitial lung disease. AB - INTRODUCTION: With an increasing number of therapeutic drugs available for use, the list of drugs that are responsible for severe pulmonary disease also grows. Genetic polymorphism of drug-metabolizing enzymes, particularly of the cytochrome P450 superfamily of enzymes, influences individual drug efficacy and safety through the alteration of pharmacokinetics and disposition of drugs. AREAS COVERED: This review focuses on drug-induced interstitial lung disease, describes common patterns of pulmonary injury, discusses diagnosis and treatment, and details the prevalence and clinical significance of cytochrome P450 polymorphisms. EXPERT OPINION: Polymorphisms of cytochrome P450 genes can influence the metabolic activity of the subsequent enzymes, which in turn may lead to localized reactions and tissue damage, for example, in lung tissue. Pharmacogenomic techniques allow efficient analysis of risk factors and genotyping tests have the potential to optimize drug therapy. In the future, genotyping should be considered to identify patients who are at high risk of severe toxic responses in order to guide appropriate individual dosage. PMID- 22070134 TI - An effective way to biosynthesize alpha-glucosyl eugenol with a high yield by Xanthomonas maltophilia. AB - CONTEXT: Eugenol is known for its analgesic, local anesthetic, anti-inflammatory, antibacterial, and hair growing effects, the application of which, however, is limited by its low solubility, liability of sublimating, and its pungent smell. Compared to eugenol, its glycosylated derivate [eugenol alpha-glucoside (alpha EG)] has more advantages in application. OBJECTIVE: The biosynthesis of alpha-EG by Xanthomonas maltophilia Hugh (Xanthomonadaceae) BT-112 and the optimum conditions for alpha-EG production are investigated here. MATERIALS AND METHODS: The alpha-EG was obtained by fermentation using Xanthomonas maltophilia BT-112 and purified by macroporous absorption resin. The identity of alpha-EG is confirmed by high performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). RESULTS: The maximum yield of alpha-EG reached 10.62 g/L broth when the suspension of Xanthomonas maltophilia strain was incubated at 30 degrees C with 70 mM eugenol and 1.0 M maltose. DISCUSSION AND CONCLUSION: Bio fermentation was applied in this work to get alpha-EG with a high mole conversion, which is a potentially efficient and highly promising approach to modify phenolic compounds into glucosides. PMID- 22070135 TI - Synthesis and structural characterization of a TCNQ based organic semi-conducting material with a 2:5 stoichiometry. AB - The tetrabutylammonium complex with a 2:5 stoichiometry, (n-Bu(4)N)(2)(TCNQ)(5), has been prepared and structurally characterized by X-ray crystallography. Diagnostic bands in the Raman spectrum and signature features in the electrochemistry confirm that the TCNQ moieties are partially charged in the solid state. EPR, magnetic susceptibility, and electrical conductivity measurements are all consistent with (n-Bu(4)N)(2)(TCNQ)(5) behaving as a quasi one-dimensional organic semiconductor. PMID- 22070137 TI - Evaluation of perceived threat differences posed by filovirus variants. AB - In the United States, filoviruses (ebolaviruses and marburgviruses) are listed as National Institute of Allergy and Infectious Diseases (NIAID) Category A Priority Pathogens, Select Agents, and Centers for Disease Control and Prevention (CDC) Category A Bioterrorism Agents. In recent months, U.S. biodefense professionals and policy experts have initiated discussions on how to optimize filovirus research in regard to medical countermeasure (ie, diagnostics, antiviral, and vaccine) development. Standardized procedures and reagents could accelerate the independent verification of research results across government agencies and establish baselines for the development of animal models acceptable to regulatory entities, such as the Food and Drug Administration (FDA), while being fiscally responsible. At the root of standardization lies the question of which filovirus strains, variants, or isolates ought to be the prototypes for product development, evaluation, and validation. Here we discuss a rationale for their selection. We conclude that, based on currently available data, filovirus biodefense research ought to focus on the classical taxonomic filovirus prototypes: Marburg virus Musoke in the case of marburgviruses and Ebola virus Mayinga in the case of Zaire ebolaviruses. Arguments have been made in various committees in favor of other variants, such as Marburg virus Angola, Ci67 or Popp, or Ebola virus Kikwit, but these rationales seem to be largely based on anecdotal or unpublished and unverified data, or they may reflect a lack of awareness of important facts about the variants' isolation history and genomic properties. PMID- 22070138 TI - Catalyst-free preparation of 1,2,4,5-tetrasubstituted imidazoles from a novel unexpected domino reaction of 2-azido acrylates and nitrones. AB - A highly efficient and convenient method for the synthesis of 1,2,4,5 tetrasubstituted imidazoles from readily accessible 2-azido acrylates and nitrones has been developed. This reaction proceeded under mild conditions without the assistance of any metal, acid, or base. PMID- 22070139 TI - Preterm birth seasonality in Greece: an epidemiological study. AB - OBJECTIVE: Seasonality of preterm birth has been noted, although not conclusively studied. Weather is also thought to play a role. We sought preterm birth seasonality and additionally studied the effect of weather parameters in the preterm birth pattern. METHODS: Vital statistics from the Hellenic Statistical Authority were retrieved, covering the years from 1980 to 2008. Additionally, weather data were retrieved for the years of the study. Time series analysis was used to create various statistical models that would be compared to each other for their accuracy to predict preterm birth. Factors used in the modeling included month of birth, gender and weather factors. RESULTS: Preterm birth seasonality was exhibited. Two peaks of higher risk of preterm birth were noted: One during summer and one during winter. Males were more influenced by seasonality and exhibited slightly different seasonal patterns than females, although no higher risk for preterm birth was noted. The best model that described seasonal pattern of preterm birth was the one that included meteorological factors. Notably, extreme (hotter or colder) weather was accompanied by an increase in preterm birth. CONCLUSIONS: Evidence for seasonality of preterm birth was shown and extreme weather was associated with a higher incidence of it. PMID- 22070141 TI - Regional differences in marital fertility in the Netherlands in the second half of the nineteenth century. AB - Abstract In the Netherlands, as in other countries, substantial regional differences in the birth rate have always been the rule rather than the exception. Of course, differences in crude birth rates may be attributed to a number of possible reasons, not all of them of primary demographic interest. For instance, according to the census of 31st December 1899, the number of women per 1,000 men in the province of Drenthe was only 924; in the province of Zuidholland the corresponding number was 1,073. It is clear that, ceteris paribus, the crude birth rate in Zuidholland would be about 7% higher than in Drenthe at that time. In such a case, the difference could reflect differences in economic development or job opportunities, factors not devoid of demographic significance, but only indirectly so. PMID- 22070142 TI - The decline of non-marital fertility in Europe, 1880-1940. AB - Abstract Between 1880 and 1940, to take approximate dates, illegitimate fertility rates in Europe dropped precipitously, falling in most countries by 50% or more. The rates used throughout this paper relate extra-marital births to the number of unmarried (i.e. single, widowed and divorced) women; we use a standardized index, I ({ih}) to be discussed later. In Fig. 1 we present most of the European series of I ( h )'s that can be computed from existing census and vital registration data. Although there are interesting exceptions the general picture is clear: a decline in illegitimate fertility commenced in most countries in the last quarter of the nineteenth century, and was arrested in the 1920's and 1930's. Once it had begun in a country, the downward course was swift and uninterrupted, until non-marital fertility had been cut in half. PMID- 22070140 TI - Ornithine decarboxylase mRNA is stabilized in an mTORC1-dependent manner in Ras transformed cells. AB - Upon Ras activation, ODC (ornithine decarboxylase) is markedly induced, and numerous studies suggest that ODC expression is controlled by Ras effector pathways. ODC is therefore a potential target in the treatment and prevention of Ras-driven tumours. In the present study we compared ODC mRNA translation profiles and stability in normal and Ras12V-transformed RIE-1 (rat intestinal epithelial) cells. While translation initiation of ODC increased modestly in Ras12V cells, ODC mRNA was stabilized 8-fold. Treatment with the specific mTORC1 [mTOR (mammalian target of rapamycin) complex 1] inhibitor rapamycin or siRNA (small interfering RNA) knockdown of mTOR destabilized the ODC mRNA, but rapamycin had only a minor effect on ODC translation initiation. Inhibition of mTORC1 also reduced the association of the mRNA-binding protein HuR with the ODC transcript. We have shown previously that HuR binding to the ODC 3'UTR (untranslated region) results in significant stabilization of the ODC mRNA, which contains several AU-rich regions within its 3'UTR that may act as regulatory sequences. Analysis of ODC 3'UTR deletion constructs suggests that cis-acting elements between base 1969 and base 2141 of the ODC mRNA act to stabilize the ODC transcript. These experiments thus define a novel mechanism of ODC synthesis control. Regulation of ODC mRNA decay could be an important means of limiting polyamine accumulation and subsequent tumour development. PMID- 22070143 TI - Estimation of demographic measures for India, 1881-1961, based on census age distributions. AB - Abstract India is one of the very few developing countries which have a relatively long history of population censuses. The first census was taken in 1872, the second in 1881 and since then there has been a census every ten years, the latest in 1971. Yet the registration of births and deaths in India, even at the present time, is too inadequate to be of much help in estimating fertility and mortality conditions in the country. From time to time Indian census actuaries have indirectly constructed life tables by comparing one census age distribution with the preceding one. Official life tables are available for all the decades from 1872-1881 to 1951-1961, except for 1911-1921 and 1931-1941. Kingsley Davis(1) filled in the gap by constructing life tables for the latter two decades. He also estimated the birth and death rates ofIndia for the decades from 1881-1891 to 1931-1941. Estimates of these rates for the following two decades, 1941-1951 and 1951-1961, were made by Indian census actuaries. The birth rates of Davis and the Indian actuaries were obtained basically by the reverse survival method from the age distribution and the computed life table of the population. Coale and Hoover(2), however, estimated the birth and death rates and the life table of the Indian population in 1951 by applying stable population theory. The most recent estimates of the birth rate and death rate for 1963-1964 are based on the results of the National Sample Survey. All these estimates are presented in summary form in Table 1. PMID- 22070144 TI - Nuptiality and population growth. AB - Abstract In the European historical experience, nuptiality patterns played a very significant role in the development of low fertility. Late marriage and widespread celibacy provided one of the mechanisms by which age-specific fertility rates were brought to low levels in the populations of Western Europe. In Eastern and Central Europe on the other hand, where marriage customarily occurred earlier and was more nearly universal, a somewhat slower fertility transition was achieved through a reduction in marital fertility - without any drastic accompanying nuptiality change. Populations of developing countries, however, commonly exhibit nuptiality patterns characterized by a still higher incidence and a considerably younger age-pattern of marriage than even the earliest observed schedule from Eastern Europe. With few exceptions, little work has been done to date to examine the implications of these very early and universal marriage schedules for fertility in general and for the growth of these populations in particular.(1) We have therefore tried to analyse the impact of nuptiality on the fertility and growth of a series of populations from developing nations where extra-marital fertility is negligible. Populations in which the prevalence of cohabitation by age is not well documented by existing marital status data (mainly those in Latin America and tropical Africa) are excluded from this analysis; an attempt will be made in later work, however, to extend the analysis to these populations. PMID- 22070145 TI - Population growth in colonial America: A study of Ipswich, Massachusetts. AB - Abstract During the colonial period, the settlements that subsequently became the United States of America experienced a tremendous growth of population. Although part of this increase was due to emigration from England and other European countries, most of the growth must be laid to the natural increase of the immigrants and their descendants. We are only beginning to probe the mechanisms ofthis increase. By numerous local studies, using the methods of historical demography that have largely been developed with work in French and English sources, we should eventually be able to describe the demographic nature of New World communities, and to understand how their populations were responding to a new physical, social and economic environment. PMID- 22070146 TI - Age at baptism in pre-industrial England. AB - Abstract The adequacy of English parish registers as demographic sources has been a subject for much debate.(1) Most attention has been directed to the problem of how far the population at large continued to use the sacraments ofthe Established Church in the late eighteenth and early nineteenth centuries, especially in areas affected by urban growth or Nonconformity. But the more general problem of how far the ecclesiastical registers of ceremonies are acceptable substitutes for registers of vital events also deserves some attention. PMID- 22070147 TI - The demography of Tristan da Cunha. AB - Abstract The eruption of the volcano on Tristan da Cunha in 1961 and the subsequent arrival of the island population in the United Kingdom provided a unique opportunity for studying the health of this formerly isolated community. During their stay, while the facilities and services of modern medicine were made available to them, investigations of many facets of their general biology were made under the auspices of the Medical Research Council, co-ordinated by Dr. H. E. Lewis. Analysis of their demographic history was essential to understand many features of their disease pattern, and the results of this analysis are presented here. They are of interest in that they not only show some consistent trends in the common variables of demography, but also demonstrate biological principles, some perhaps for the first time in man, which may be fundamental in the process of colonization as a biological phenomenon, e.g. the initial difficulty of establishment of a population in a new area, the curious demographic structure that may emerge in its earliest years, the bottleneck effect of population-size reduction, the founder principle. PMID- 22070148 TI - Changes in fertility rates and family size in response to changes in age at marriage, the trend away from arranged marriages, and increasing urbanization. AB - Abstract Demographers have proposed a long list of factors that help explain why population growth and fertility rates respond to rising levels of urbanization, economic growth and national development.(2) Two of the many suggested influences will be investigated in the present paper with regard to urban Hong Kong. PMID- 22070149 TI - Timing and sequence of resuming ovulation and menstruation after childbirth. AB - Abstract This report presents results from a prospective study of post-partum physiology conducted by the Obstetric Department of the Catholic University of Chile during 1965-68. The study was undertaken to gain more detailed knowledge than is currently available about the relationship between a woman's lactation experience and the return of her post-partum reproductive function. 200 mothers were successfully followed and information collected about their intervals from childbirth to first ovulation and to first bleeding day, together with a detailed history of breast feeding. In these histories, days of 'full breast feeding' (infant exclusively breast-fed) are distinguished from days of 'partial breast feeding' (infant given supplementary nutrition besides breast milk). Elaborate pains were taken to establish the date of first ovulation, four different techniques being used concurrently during a series of weekly contacts with each patient. PMID- 22070150 TI - Breast feeding, mortality in childhood and fertility in a rural zone of Senegal. AB - Abstract The data analysed in the present study were collected in the course of a demographic survey conducted at repeated intervals in the Sine-Saloum region of Senegal. 1 This study was financed by a grant from the 'Fond d'aide et de cooperation' of France, from 1963-65, and by the WHO Section for Research on Human Reproduction from 1966-67. The study was conducted by ORSTOM in collaboration with the Statistical Service of Senegal. The data used in this paper were analysed at INED. Only the data concerning the Sine (Niakhar) area are analysed here. PMID- 22070151 TI - Contraceptive overlap with post-partum anovularity. AB - Abstract Contraceptive use in the early post-partum months is, for the majority of women, without any direct protective value because, whilst not ovulating, they are not exposed to the risk of pregnancy. This does not, of course, imply that contraception should be delayed until signs of the resumption of ovulation appear, as for many women the first sign of such resumption is pregnancy. There are, besides, logistic and psychological reasons which make early post-partum contraception advisable. It does, however, demand that any calculation of the demographic effects of contraceptive use should make due allowance for this null period of use. PMID- 22070152 TI - Erratum. PMID- 22070155 TI - Neutralizing antibodies against rotavirus produced in transgenically labelled purple tomatoes. AB - Edible fruits are inexpensive biofactories for human health-promoting molecules that can be ingested as crude extracts or partially purified formulations. We show here the production of a model human antibody for passive protection against the enteric pathogen rotavirus in transgenically labelled tomato fruits. Transgenic tomato plants expressing a recombinant human immunoglobulin A (hIgA_2A1) selected against the VP8* peptide of rotavirus SA11 strain were obtained. The amount of hIgA_2A1 protein reached 3.6 +/- 0.8% of the total soluble protein in the fruit of the transformed plants. Minimally processed fruit derived products suitable for oral intake showed anti-VP8* binding activity and strongly inhibited virus infection in an in vitro virus neutralization assay. In order to make tomatoes expressing hIgA_2A1 easily distinguishable from wild-type tomatoes, lines expressing hIgA_2A1 transgenes were sexually crossed with a transgenic tomato line expressing the genes encoding Antirrhinum majus Rosea1 and Delila transcription factors, which confer purple colour to the fruit. Consequently, transgenically labelled purple tomato fruits expressing hIgA_2A1 have been developed. The resulting purple-coloured extracts from these fruits contain high levels of recombinant anti-rotavirus neutralizing human IgA in combination with increased amounts of health-promoting anthocyanins. PMID- 22070156 TI - Feasibility of pedometers for adults with schizophrenia: pilot study. AB - The purpose of this prospective and observational design study was to assess the feasibility of using a pedometer and step log to explore level of physical activity (PA) and to assess motivation to be physically active in adults with schizophrenia. Descriptive statistics were used to analyse data of 7 male and 5 female subjects. Pedometer data indicated that subjects walked an average of 4731.03 (+/-3318.19) steps and 5002.58 (+/-3041.03) during the first week and second week of the study, respectively. A minimum 30-min walk was recorded on an average of 3.67 (+/-1.82) days (week one) and 4.5 (+/-1.88) days (week two). Step logs, inconsistently maintained by subjects, were not able to be analysed. Examination of the Motives for Physical Activity Measure-Revised (MPAM-R) at baseline indicates that exercise fitness and body appearance were subjects' primary motives for PA participation. Study findings indicate that it is feasible to use a pedometer to monitor the level of PA. However, maintenance of a concurrent step log requires further consideration to determine realistic outcomes. Extrinsically focused motivations for PA in this study sample may predict low PA adherence. PMID- 22070157 TI - Medicinal plants and dementia therapy: herbal hopes for brain aging? AB - An escalating "epidemic" of diseases like Alzheimer's has not yet been met by effective symptomatic treatments or preventative strategies. Among a few current prescription drugs are cholinesterase inhibitors including galantamine, originating from the snowdrop. Research into ethnobotanicals for memory or cognition has burgeoned in recent years. Based on a multi-faceted review of medicinal plants or phytochemicals, including traditional uses, relevant bioactivities, psychological and clinical evidence on efficacy and safety, this overview focuses on those for which there is promising clinical trial evidence in people with dementia, together with at least one other of these lines of supporting evidence. With respect to cognitive function, such plants reviewed include sage, Ginkgo biloba, and complex mixtures of other traditional remedies. Behavioral and psychological symptoms of dementia (BPSD) challenge carers and lead to institutionalization. Symptoms can be alleviated by some plant species (e.g., lemon balm and lavender alleviate agitation in people with dementia; St John's wort treats depression in the normal population). The ultimate goal of disease prevention is considered from the perspective of limited epidemiological and clinical trial evidence to date. The potential value of numerous plant extracts or chemicals (e.g., curcumin) with neuroprotective but as yet no clinical data are reviewed. Given intense clinical need and carer concerns, which lead to exploration of such alternatives as herbal medicines, the following research priorities are indicated: investigating botanical agents which enhance cognition in populations with mild memory impairment or at earliest disease stages, and those for BPSD in people with dementia at more advanced stages; establishing an ongoing authoritative database on herbal medicine for dementia; and further epidemiological and follow up studies of promising phytopharmaceuticals or related nutraceuticals for disease prevention. PMID- 22070158 TI - AFLP markers reveal high clonal diversity and extreme longevity in four key arctic-alpine species. AB - We investigated clonal diversity, genet size structure and genet longevity in populations of four arctic-alpine plants (Carex curvula, Dryas octopetala, Salix herbacea and Vaccinium uliginosum) to evaluate their persistence under past climatic oscillations and their potential resistance to future climate change. The size and number of genets were determined by an analysis of amplified fragment length polymorphisms and a standardized sampling design in several European arctic-alpine populations, where these species are dominant in the vegetation. Genet age was estimated by dividing the size by the annual horizontal size increment from in situ growth measurements. Clonal diversity was generally high but differed among species, and the frequency distribution of genet size was strongly left-skewed. The largest C. curvula genet had an estimated minimum age of c. 4100 years and a maximum age of c. 5000 years, although 84.8% of the genets in this species were <200 years old. The oldest genets of D. octopetala, S. herbacea and V. uliginosum were found to be at least 500, 450 and 1400 years old, respectively. These results indicate that individuals in the studied populations have survived pronounced climatic oscillations, including the Little Ice Age and the postindustrial warming. The presence of genets in all size classes and the dominance of presumably young individuals suggest repeated recruitment over time, a precondition for adaptation to changing environmental conditions. Together, persistence and continuous genet turnover may ensure maximum ecosystem resilience. Thus, our results indicate that long-lived clonal plants in arctic alpine ecosystems can persist, despite considerable climatic change. PMID- 22070159 TI - Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care--the ProGERD study. AB - BACKGROUND: The evolution of gastro-oesophageal reflux disease (GERD) under current management options remains uncertain. AIM: To examine whether, depending on the initial presentation, non-erosive (NERD) and erosive reflux disease (ERD) without Barrett's oesophagus will progress to more severe disease under current routine care following the resolution of the initial condition. METHODS: Patients with the primary symptom of heartburn were included at baseline, and stratified into non-erosive (NERD) and erosive reflux disease (ERD), LA grades A-D (Los Angeles classification). After a 2- to 8-week course with esomeprazole therapy to achieve endoscopic healing in ERD and symptom relief in NERD, patients were treated routinely at the discretion of their physician. We report oesophagitis status and the presence of endoscopic and confirmed Barrett's oesophagus after 5 years. RESULTS: A total of 6215 patients were enrolled in the study of whom 2721 patients completed the 5-year follow-up. Progression, regression and stability of GERD severity were followed from baseline to 5 years. Only a few patients with NERD and mild/moderate ERD progressed to severe forms of ERD and even Barrett's oesophagus. Most patients remained stable or showed improvement in their oesophagitis; 5.9% of the NERD patients, 12.1% of LA grade A/B patients and 19.7% of LA grade C/D patients in whom no Barrett's oesophagus was recorded at baseline progressed to endoscopic or confirmed Barrett's oesophagus at 5 years. CONCLUSION: Most GERD patients remain stable or improve over a 5-year observation period under current routine clinical care. PMID- 22070160 TI - Recovery: what mental health nurses and service users say about the concept of recovery. AB - This study presents a thematic analysis of focus group talk to examine what recovery in mental health means to service users and nurses. Data were collected from two focus groups, one group of service users and one group of nurses. The service user group (n=6) were adults with previous or recent experience of inpatient mental health services. The nursing group were registered nurses (n=5) of various grades and experience currently working in inpatient mental health services in one region of the U.K. Thematic analysis using Krueger and Casey's framework led to four themes being developed. These were 'understandings of recovery', 'semantics', 'therapeutics' and 'a journey'. While the recovery concept was not new to either group, understandings of recovery were vague and contradictory. PMID- 22070161 TI - Medication safety: using incident data analysis and clinical focus groups to inform educational needs. AB - RATIONALE, AIMS AND OBJECTIVES: Medication-related safety incidents are a source of concern to patients, policy makers and clinicians. The role of education in improving safety-critical practices in health care is poorly appreciated. This pilot study aimed to initiate collective discussion among professional groups of clinical staff about a range of medicine-related patient safety issues which were identified from a local incident reporting system. In engaging staff to collectively reflect on reported medication incidents we attempted to uncover a deeper understanding of local contextual issues and potential educational needs. METHODS: A mixed method study was conducted involving categorical analysis of 1058 medication incident reports (Phase 1) and the use of three mixed focus groups of clinical staff (Phase 2) in three acute hospitals in one locality in NHS Scotland. RESULTS: Focus group transcript analysis produced four main themes (e.g. the medical role) and 12 related sub-themes (e.g. pharmacological education and skill mix for administration of medicines) concerning medication-related practices and possible educational interventions. CONCLUSIONS: While it is necessary to review reported incident data and disseminate the educational messages for the improvement of quality, this traditional risk management process is inadequate on its own. Reporting systems can be enhanced by collective examination of reported information about medicines by local clinical teams. We identified a strong message from the focus groups for learning about each other and from each other, and that the method piloted may be an important inter professional mechanism for improvement. PMID- 22070162 TI - Lipid metabolism and other metabolic changes in vervet monkeys experimentally infected with Trypanosoma brucei rhodesiense. AB - BACKGROUND: Human African trypanosomiasis is associated with metabolic changes which have not been well characterized. METHODS: Chlorocebus aethiops were experimentally infected with Trypanosoma brucei rhodesiense and late-stage disease induced at 28 days post-infection. Ear prick blood for glucose determination and blood samples were obtained at weekly intervals for 56 days. Analysis was carried out using dry chemistry analysis. RESULTS: In early infection, there was a significant increase in creatine kinase, while during early and transitional stage of infection there was a significant decrease in glucose and high-density lipoprotein and an increase in triglyceride levels. In the late stage, there was a significant increase in both total cholesterol and LDL levels. CONCLUSIONS: Further investigations should focus on levels of total cholesterol during the follow-up period in curatively treated vervet monkeys. Apart from their importance in disease staging, the changes in lipids levels may also affect the pharmacokinetics of some trypanocides. PMID- 22070163 TI - Steric modifications tune the regioselectivity of the alkane oxidation catalyzed by non-heme iron complexes. AB - Iron complexes with the tetradentate N-donor ligand N,N'-di(phenylmethyl)-N,N' bis(2-pyridinylmethyl)-1,2-cyclohexanediamine (bbpc) are reported. Despite the benzyl groups present on the amines, the iron compounds catalyze the oxygenation of cyclohexane to an extent similar to those employing less sterically encumbered ligands. The catalytic activity is strongly dependent on the counterion, with the highest activity and the strongest preference for alkane hydroxylation correlating to the most weakly coordinating anion, SbF(6)(-). The selectivity for the alcohol product over the ketone is amplified when acetic acid is present as an additive. When hydrocarbon substrates with both secondary and tertiary carbons are oxidized by H(2)O(2), the catalyst directs oxidation toward the secondary carbons to a greater degree than other previously reported iron-containing homogeneous catalysts. PMID- 22070164 TI - Arts In-Reach: taking 'bricks off shoulders' in adult mental health inpatient care. AB - This article reports upon a research study focusing on a programme of work called Arts In-Reach. The programme was designed to provide a participatory arts programme for the adult mental health inpatient wards in a city in the UK. The aim of the research study was to explore the experiences of people who have engaged with the Arts In-Reach programme of work. Eleven qualitative interviews were conducted among participants of the programme. Consistent with other research, this study reveals how people on the wards often feel powerless and bored. The feelings of boredom are exacerbated as people recover. Participating in the arts groups has alleviated some of those feelings. Furthermore, participation has also increased people's social interactions and given opportunity for self-expression. The arts activities also provide a distraction for people and some appreciated being able to talk about matters other than their 'illness'. The arts activities helped people to think about their future and how they might take their artwork forward. For some people, thinking about the future helped with restoring a sense of hope, a quality imperative for recovery. PMID- 22070165 TI - Clinical evaluation of severe anemia in pregnancy with special reference to macrocytic anemia. AB - AIMS: Anemia in pregnancy has been almost synonymous with iron-deficiency anemia but there appears to be a changing trend with emerging evidence of macrocytic anemia. The aim of this study was to evaluate the clinical profile of patients having severe anemia in pregnancy. METHODS: This study included all antenatal patients presenting with severe anemia (hemoglobin<7gm%) over a period of 2years from January 2008 to December 2009 in the Department of Obstetrics and Gynaecology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi. RESULTS: Although iron-deficiency anemia remains the most important cause of anemia (48.1%) there is also a high prevalence of macrocytic anemia (40%) amongst these cases of severe anemia in pregnancy. The maternal and fetal morbidity and mortality is higher in macrocytic anemia as compared to iron-deficiency anemia. CONCLUSION: There is an emerging trend of macrocytic anemia among antenatal patients with severe anemia. Both maternal and fetal morbidity appears to be higher in these cases. This has important implications in terms of diagnosis and therapy to optimize both maternal and perinatal outcomes. Once clinicians and health administrators recognize the magnitude of this problem it may be considered relevant to start public health interventions by way of requirement of appropriate food fortification. PMID- 22070166 TI - The catechol-O-methyltransferase (COMT) Val158Met polymorphism moderates the effect of antenatal stress on childhood behavioural problems: longitudinal evidence across multiple ages. AB - AIM: The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene was analysed to determine its association with maternal stress and childhood total difficulties. METHOD: Data were collected at birth from a group of infants who were born small for gestational age and a group who were born at an appropriate size for gestational age and had been enrolled in the Auckland Birthweight Collaborative Study. Children were followed up at the ages of 1 year, 3 years 6 months, 7 years, and 11 years. At the age of 11 years, DNA samples were collected from 546 children (270 females, 276 males): 227 children born small for gestational age and 319 children born at an appropriate size for gestational age. The main independent variable was perceived maternal stress at birth and at 7 and 11 years of age, assessed using the total difficulties scale of the Strength and Difficulties Questionnaire. IQ was assessed at the age of 7 years. RESULTS: Met/Met homozygotes were at a significantly increased risk of behavioural and emotional problems at the ages of 7 (p=0.002) and 11 years (p=0.003), relative to either heterozygous or homozygous carriers of the Val158Met polymorphism, but only when they were exposed to maternal stress in utero. Met/Met homozygotes had, on average, IQ scores that were four points higher than those of Val/Val homozygotes (p=0.010). INTERPRETATION: These findings emphasize the potential long-term consequences of prenatal stress for genetically susceptible individuals during neurodevelopment in utero. Our findings add to the general understanding of the aetiology and developmental nature of childhood emotional and behavioural problems. PMID- 22070168 TI - Amphiphilic behavior of new cholesteryl cyclodextrins: a molecular study. AB - Amphiphilic cyclodextrins (CDs) are good candidates to functionalize natural membranes as well as synthetic vesicles. In this paper, we describe the synthesis of the amphiphilic permethylated monocholesteryl alpha-CD (TASC). Its interfacial behavior is compared with that of the permethylated mono- and dicholesteryl beta CD analogues (TBSC and TBdSC). Langmuir isotherms suggest a reorganization upon compression for all compounds, which is quantified using neutron as well as X-ray reflectivity. The in-plane structure is characterized by atomic force microscopy (AFM) on monolayers deposited on solid substrates. A model involving a reorientation of the CD with respect to the interface to adjust its conformation to the available area per molecule is proposed. Although we observe for TBSC a rearrangement similar to TASC and TBdSC, it is already achieved at lower surface pressures compared with its disubstituted derivative. This specific behavior is explained by an increased structural flexibility and compressibility compared with TBdSC and TASC. The average number of water molecules per CD was determined using the neutron data and validated from X-ray data, which also allows the determination of the CD's molecular volume. The permethylated CD molecules are strongly hydrated in the film, but the alpha-CD analogue is less hydrated than the beta-CD derivatives, and hydration decreases with compression. PMID- 22070167 TI - ProPhylo: partial phylogenetic profiling to guide protein family construction and assignment of biological process. AB - BACKGROUND: Phylogenetic profiling is a technique of scoring co-occurrence between a protein family and some other trait, usually another protein family, across a set of taxonomic groups. In spite of several refinements in recent years, the technique still invites significant improvement. To be its most effective, a phylogenetic profiling algorithm must be able to examine co occurrences among protein families whose boundaries are uncertain within large homologous protein superfamilies. RESULTS: Partial Phylogenetic Profiling (PPP) is an iterative algorithm that scores a given taxonomic profile against the taxonomic distribution of families for all proteins in a genome. The method works through optimizing the boundary of each protein family, rather than by relying on prebuilt protein families or fixed sequence similarity thresholds. Double Partial Phylogenetic Profiling (DPPP) is a related procedure that begins with a single sequence and searches for optimal granularities for its surrounding protein family in order to generate the best query profiles for PPP. We present ProPhylo, a high-performance software package for phylogenetic profiling studies through creating individually optimized protein family boundaries. ProPhylo provides precomputed databases for immediate use and tools for manipulating the taxonomic profiles used as queries. CONCLUSION: ProPhylo results show universal markers of methanogenesis, a new DNA phosphorothioation-dependent restriction enzyme, and efficacy in guiding protein family construction. The software and the associated databases are freely available under the open source Perl Artistic License from ftp://ftp.jcvi.org/pub/data/ppp/. PMID- 22070169 TI - Polycaprolactone scaffolds fabricated with an advanced electrohydrodynamic direct printing method for bone tissue regeneration. AB - Electrohydrodynamic (EHD) direct writing has been used in diverse microelectromechanical systems and various supplemental methods for biotechnology and electronics. In this work, we expanded the use of EHD-induced direct writing to fabricate 3D biomedical scaffolds designed as porous structures for bone tissue engineering. To prepare the scaffolds, we modified a grounded target used in conventional EHD direct printing using a poly(ethylene oxide) solution bath, elastically cushioning the plotted struts to prevent crumbling. The fabricated scaffolds were assessed for not only physical properties including surface roughness and water uptake ability but also biological capabilities by culturing osteoblast-like cells (MG63) for the EHD-plotted polycaprolactone (PCL) scaffold. The EHD-scaffolds showed significantly roughened surface and enhanced water absorption ability (400% increase) compared with the pure rapid-prototyped PCL. The results of cell viability, alkaline phosphatase activity, and mineralization analyses showed significantly enhanced biological properties of the scaffold (20 times the cell viability and 6 times the mineralization) compared with the scaffolds fabricated using RP technology. Because of the results, the modified EHD direct-writing process can be a promising method for fabricating 3D biomedical scaffolds in tissue engineering. PMID- 22070170 TI - Sorption-desorption of indaziflam in selected agricultural soils. AB - Indaziflam, a new alkylazine herbicide that inhibits cellulose biosynthesis, is under current development for soil applications in perennial crops and nonagricultural areas. Sorption and desorption of indaziflam in six soils from Brazil and three soils from the United States, with different physical chemical properties, were investigated using the batch equilibration method. Sorption kinetics demonstrated that soil-solution equilibrium was attained in <24 h. The Freundlich equation described the sorption behavior of the herbicide for all soils (R(2) > 0.99). K(f) values of the Brazilian oxisols ranged from 4.66 to 29.3, and 1/n values were >= 0.95. Sorption was positively correlated to %OC and clay contents. U.S. mollisol K(f) values ranged from 6.62 to 14.3; 1/n values for sorption were >= 0.92. K(f) values from mollisols were also positively correlated with %OC. These results suggest that indaziflam potential mobility, based solely on its sorption coefficients, would range from moderate to low in soil. Desorption was hysteretic on all soils, further decreasing its potential mobility for offsite transport. PMID- 22070172 TI - Status of National Family Planning Programmes of Developing Countries in relation to demographic targets. AB - Abstract Having arisen within the context of social and economic development plans, demographic targets associated with family planning programmes in developing countries stipulate levels deemed desirable or necessary to implement economic goals. Since an optimum fertility path for economic development is open to conjecture, targets tend to be vague or arbitrary, and generally imply a fertility decline that goes beyond family limitation based on health considerations. While on the one hand, programme administrators have assumed responsibility for these targets, on the other hand they have structured their programmes toward health, not demographic, goals. As a result, they have minimized rather tham maximized the contribution of the programmes to the targets. of the 24 countries with programmes designed to reduce birth rates, the demographic variable is on target in seven; in six, review is premature; five cannot be evaluated because targets are non-quantifiable or vital data are too uncertain; and in six, including India and Pakistan, progress has been poor, at least in relation to targets. The demographic target is only one of many models and techniques for programme evaluation, although many require data not often available in developing countries. An estimate of births averted based directly on programme activities is not only complex but speculative. However, in contrast to the target criterion, cost benefit analyses involving the estimated return for an averted birth indicate that the programmes are a highly profitable investment. PMID- 22070173 TI - The Validation of Brass's Model Life Table System. AB - Abstract The closeness-of-fit of two-parameter Brass model life-tables to English life-tables is examined. This is done for various life-table functions and various criteria of best fit. Reproductions of computer output give full details of the fits for typical cases from the large selection of cases examined. It was found that the equations to be solved to find the best fit were intractable and the paper gives a simple method of finding an approximate solution to these equations. PMID- 22070174 TI - Models for the estimation of the probability of dying between birth and exact ages of early childhood. AB - Abstract This paper develops two models, each of which is designed to estimate the probability of surviving from birth to selected exact ages of early childhood: namely ages two, three and five. The models are designed for use in areas with deficient registration systems. They require, as input, statistics which can be derived from retrospective data supplied by census or survey respondents. The first model, the age model, converts statistics on the proportion dead of children ever born to women in age groups 20-24, 25-29 and 30 34 into estimates of q2, q3 and q5. The second model, the marriage model, converts statistics on the proportion dead of children ever born to women of five year marriage duration intervals into these estimates. The models can be used independently or simultaneously. These models were developed from data generated by a large number of empirical fertility and mortality schedules. Regression analysis was used to determine the parameter values of the relationships specified, and several sets of equations for estimating values of qa, for a = 2, 3 and 5 comprise the final product of the paper. It should be noted that the conceptual basis for the models was first derived by William Brass. The data generated for the regression analysis provided an opportunity to test the original Brass estimated model. We are able to report that the model performed well over the wide range of fertility and mortality conditions included in the test. PMID- 22070175 TI - Neo-natal and post-neo-natal mortality in a rural area of Bangladesh. AB - Abstract An analysis of neo-natal and post-neo-natal mortality in 132 villages (population of 117,000) of Matlab thana indicates the following: (i) Neo-natal deaths accounted for 60% of the infant mortality rate of 125. This proportion was unexpectedly high since previous research had maintained that in countries with infant mortality rates over 100, neo-natal deaths account for less than one-third of all infant deaths. Since the present findings on the proportions of neo-natal deaths correspond exactly with results from an earlier registration system in East Pakistan, it is suggested that the long-accepted proposition, 'less developed' areas are characterized by lower proportions of neo-natal deaths than 'more developed' areas, be re-examined. (2) The infant death rate accounts for 36% of all deaths in the population. If the infant death rate were reduced by half the result would be a decrease in the current crude death rate from 16 to 13. Although this reduction would appear to be small, in the context of a current high growth rate of 3% (from 1966-67 to 1968-69) it exerts a sizeable impact. For example, it would take a reduction of eight points in the crude birth rate of 46 just to achieve a growth rate 2.5% under these circumstances. Obviously, continued efforts in death control without an effective birth control programme will perpetuate high rates of growth. (3) Neo-natal and post-neo-natal mortality exhibited the -expected 'U' shaped pattern with parity, and generally varied as expected with age and family size, except in the oldest age group and largest family size where the risk was smaller than in the preceding groups. An explanation for these findings is presented, based on the effect that births to high-parity women with low child mortality have upon the total neo-natal and post neo-natal mortality rates. It was found that these births exhibit a much lower mortality risk than births to women of comparable parities and higher child mortality, and that their numbers account for the lower risk to the births in the oldest age group and largest family size. It was concluded that women with a combination of high parity and low child mortality most probably represent a group with superior socio-economic and or health conditions which contribute to the lower risk of neo-natal and post-neo-natal death. PMID- 22070178 TI - Effects of ArF excimer laser irradiation of dentin on the tensile bonding strength to composite resin. AB - OBJECTIVE: The purpose of the study was to evaluate the effects of argon fluoride (ArF) excimer laser irradiation on the tensile bonding strength (TBS) of dentin to composite resin. BACKGROUND DATA: Dental lasers use a photothermal process, which potentially entails risk of tissue damage caused by heat affecting the bond strength of resins. The ArF excimer laser functions by a photochemical process in which the energy of photons directly cuts covalent bonds in molecules without generating heat. METHODS: Twenty extracted human molars were sectioned perpendicularly to the tooth axis to expose a flat dentin surface. The surfaces were treated with various combinations of ArF excimer laser irradiation, primer treatment, and bonding treatment. After composite resin was built up on the treated dentin surface, specimens with a 1*1 mm bonding interface were prepared and subjected to TBS tests. Treated dentin surfaces were also observed using transmission electron microscopy (TEM). RESULTS: Specimens that underwent laser irradiation followed by bonding treatment had a TBS that did not differ significantly from that of specimens that received conventional treatment, with or without priming. TEM observations showed sectioned and dispersed collagen matrix in the hybrid layer after laser irradiation, priming, and bonding, but no hybrid layer after laser irradiation and bonding at the treated dentin surface. CONCLUSIONS: The TBS of conditioning with ArF excimer laser irradiation was identical to that with conventional treatment when bonding was used. The bonding mechanism with the ArF irradiation differed from that of conventional bonding depending upon dentin hybridization. PMID- 22070179 TI - Contrast enhancement on computed tomography after renal cryoablation: an evidence of treatment failure? AB - BACKGROUND AND PURPOSE: Renal cryoablation has gained popularity as a treatment option for localized renal masses. Treatment success is typically defined by the absence of contrast enhancement on follow-up imaging. We investigate the evolution of lesions that demonstrate contrast enhancement on CT after renal cryoablation. PATIENTS AND METHODS: Retrospective review of records of laparoscopic and percutaneous cryoablation (LCA and PCA) was performed, identifying records with postoperative radiographic enhancement. Imaging studies were reviewed and radiographic (pre- and post-contrast Hounsfield units, pattern and location of enhancement) and clinical data including follow up were collected. RESULTS: One hundred and seventy-two cryoablation procedures were analyzed. Of these, 30 (17.4%) showed enhancement on follow-up CT. In 28 cases, contrast enhancement was demonstrated on the first postoperative study. Seven patients underwent salvage treatments. Spontaneous resolution of enhancement was noted in 17 (56.7%) cases. No association was found between enhancement pattern (diffuse/nodular/rim) and resolution. Of lesions enhancing >35 HU, only 14.3% resolved spontaneously. Delayed enhancement (after negative imaging studies) occurred in two patients; both underwent salvage treatments. CONCLUSIONS: Most of the time, contrast-enhancements after cryoablation are evident on the first follow-up imaging study. More than 50% of these resolve spontaneously, and only one of four patients need salvage treatment. Delayed appearance of enhancement after previously negative imaging and highly enhancing lesions (>35 HU) are unlikely to resolve and should be considered suspicious for local recurrence or incomplete ablation. Further investigation is warranted to reach a consensus on a radiographic definition of local recurrence after renal cryoablation. PMID- 22070181 TI - Defining treatment response in pediatric tic disorders: a signal detection analysis of the Yale Global Tic Severity Scale. AB - OBJECTIVE: To examine the optimal Yale Global Tic Severity Scale (YGTSS) percent reduction and raw cutoffs for predicting treatment response among children and adolescents with tic disorders. METHOD: Youth with a tic disorder (N=108; range=5 17 years) participated in several clinical trials involving varied medications or psychosocial treatment, or received naturalistic care. Assessments were conducted before and after treatment and included the YGTSS and response status on the Clinical Global Impressions-Improvement Scale (CGI-I). RESULTS: A 35% reduction on the YGTSS total tic severity score or a YGTSS raw total tic severity score change of 6 or 7 points were the best indicators of clinical treatment response in youth with tic disorders. CONCLUSIONS: A YGTSS total tic severity score reduction of 35% or a raw total tic severity score change of 6 or 7 appears optimal for determining treatment response. A consistent definition of treatment response on the YGTSS may facilitate cross-study comparability. Practitioners can use these values for treatment planning decisions (e.g., change medications, etc.). PMID- 22070180 TI - Risperidone-related improvement of irritability in children with autism is not associated with changes in serum of epidermal growth factor and interleukin-13. AB - Risperidone has been shown to improve serious behavioral problems in children with autism. Here we asked whether risperidone-associated improvement was related to changes in concentrations of inflammatory molecules in the serum of these subjects. Seven molecules were identified as worthy of further assessment by performing a pilot analysis of 31 inflammatory markers in 21 medication-free subjects with autism versus 15 healthy controls: epidermal growth factor (EGF), interferon-gamma (IFN-gamma), interleukin (IL)-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), IL-1 and IL-1-receptor antagonist. Serum concentrations of these markers were then established in a different set of subjects that participated in a double-blind, clinical trial and an expanded group of healthy subjects. In the first analysis, samples obtained from subjects with autism at baseline visits were compared to visits after 8-week treatment with placebo (n=37) or risperidone (n=40). The cytokine concentrations remained stable over the 8-week period for both risperidone and placebo groups. In the second analysis, we explored further the differences between medication-free subjects with autism (n=77) and healthy controls (recruited independently; n=19). Serum levels of EGF were elevated in subjects with autism (median=103 pg/mL, n=75) in comparison to healthy controls (75 pg/mL, n=19; p<0.05), and levels of IL-13 were decreased in autism (median=0.8 pg/mL, n=77) in comparison to controls (9.8 pg/mL, n=19; p=0.0003). These changes did not correlate with standardized measures used for a diagnosis of autism. In summary, risperidone-induced clinical improvement in subjects with autism was not associated with changes in the serum inflammatory markers measured. Whether altered levels of EGF and IL-13 play a role in the pathogenesis or phenotype of autism requires further investigation. PMID- 22070182 TI - Placental magnetic resonance imaging in monochorionic twin pregnancies. AB - OBJECTIVE: Twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic pregnancies. Placental hydrops might be a marker for TTTS. The purpose of this study was to evaluate whether differences in the placental parenchyma due to TTTS can be seen with fetal MRI. METHODS: In a retrospective study, 34 monochorionic pregnancies were investigated on a 1.5 Tesla MR. Seventeen pregnancies were affected by TTTS, and 17 showed no clinical signs of TTTS. Placental maturation and vascular pathologies, as well as the extent of the placental findings and allocation of placental tissue to each twin, were investigated. Placental findings were reported for origin, size, maturation, and placental thickness, and were correlated with the presence of TTTS. RESULTS: All placentas affected by TTTS showed abnormal maturation on MR scans, but only 64.7% of the non-TTTS group (p = 0.018). Vascular placental pathologies did not differ significantly between the TTTS and non-TTTS group. CONCLUSIONS: MR-signs of placental maturity in monochorionic twin pregnancies may indicate a lower risk of development of TTTS. PMID- 22070183 TI - Pd(0)-catalyzed oxy- and aminoalkynylation of olefins for the synthesis of tetrahydrofurans and pyrrolidines. AB - The first Pd(0)-catalyzed intramolecular oxy- and aminoalkynylation of nonactivated olefins is reported. The reaction gives access to important tetrahydrofuran and pyrrolidine heterocycles with high diastereoselectivity. The unique synthetic potential of acetylenes is further exploited to access key building blocks for the synthesis of bioactive natural products. PMID- 22070184 TI - Anticholinergics for overactive bladder therapy: central nervous system effects. AB - The mainstay of pharmacological treatment of overactive bladder (OAB) is anticholinergic therapy using muscarinic receptor antagonists (tertiary or quaternary amines). Muscarinic receptors in the brain play an important role in cognitive function, and there is growing awareness that antimuscarinic OAB drugs may have adverse central nervous system (CNS) effects, ranging from headache to cognitive impairment and episodes of psychosis. This review discusses the physicochemical and pharmacokinetic properties of OAB antimuscarinics that affect their propensity to cause adverse CNS effects, as observed in phase III clinical trials and in specific investigations on cognitive function and sleep architecture. PubMed/MEDLINE was searched for "OAB" plus "muscarinic antagonists" or "anticholinergic drug." Additional relevant literature was identified by examining the reference lists of papers identified through the search. Preclinical and clinical trials in adults were assessed, focusing on the OAB antimuscarinics approved in the United States. The blood-brain barrier (BBB) plays a key role in protecting the CNS, but it is penetrable. The lipophilic tertiary amines, particularly oxybutynin, are more likely to cross the BBB than the hydrophilic quaternary amine trospium chloride, for which there are very few reports of adverse CNS effects. In fact, in 2008 the US product labels for oral oxybutynin were modified to include the potential for anticholinergic CNS events and a warning to monitor patients for adverse CNS effects. Even modest cognitive impairment in the elderly may negatively affect independence; therefore, selection of an antimuscarinic OAB drug with reduced potential for CNS effects is advisable. PMID- 22070185 TI - Iron-catalyzed regioselective direct oxidative aryl-aryl cross-coupling. AB - Regioselective iron-catalyzed cross-dehydrogenative coupling (CDC) of two aromatic compounds using tert-BuOOH as oxidant under mild conditions has been reported. The direct oxidative coupling reaction is selective toward creation of a carbon-carbon bond at the position ortho to the functional groups of the substrates, completely preventing the homocoupled products. The C-C bond-forming reaction makes the method versatile, leading to functionalized 2,2' disubstituted biaryls. PMID- 22070186 TI - A synthesis of existing systematic reviews and meta-analyses of school-based behavioural interventions for controlling and preventing obesity. AB - Schools are an attractive and popular setting for implementing interventions for children. There is a growing body of empirical research exploring the efficacy of school-based obesity prevention programs. While there have been several reviews on the topic, findings remain mixed. To examine the quality of evidence and compare the findings from existing systematic reviews and meta-analyses of school based programs in the prevention and control of childhood obesity. This paper systematically appraises the methodology and conclusions of literature reviews examining the effectiveness of school-based obesity interventions published in English in peer-reviewed journals between January 1990 and October 2010. Eight reviews were examined, three meta-analyses and five systematic reviews. All of the reviews recognized that studies were heterogeneous in design, participants, intervention and outcomes. Intervention components in the school setting associated with a significant reduction of weight in children included long-term interventions with combined diet and physical activity and a family component. Several reviews also found gender differences in response to interventions. Of the eight reviews, five were deemed of high quality and yet limited evidence was found on which to base recommendations. As no single intervention will fit all schools and populations, further high-quality research needs to focus on identifying specific program characteristics predictive of success. PMID- 22070187 TI - Nationwide linkage analysis in Scotland to assess mortality following hospital admission for Crohn's disease: 1998-2000. AB - BACKGROUND: Although population-based studies of patients with Crohn's disease (CD) suggest only a modestly increased mortality, recent data have raised concerns regarding the outcome of CD patients requiring hospitalisation. AIM: To determine the mortality and contributory factors in 1595 patients hospitalised for CD in Scotland between 1998 and 2000. METHODS: The Scottish Morbidity Records database and linked datasets were used to assess longitudinal patient outcome, and to explore associations between 3-year mortality and age, sex, comorbidity, admission type and social deprivation. The standardised mortality ratio (SMR) at 3 years from admission was calculated with reference to the Scottish population. RESULTS: The SMR was 3.31 (95% confidence interval 2.80-3.89). This was increased in all patients, other than those <30 years at presentation, and was highest in patients aged 50-64 years (SMR 4.84 [3.44-6.63]). On multivariate analysis, age >50, admission type, comorbidity, social deprivation and length of admission were significantly associated with mortality. Other than age, admission type was the strongest factor predictive of death. Three-year crude mortality was 0.3% for elective surgical, 8.7% for emergency surgical, 8.3% for elective nonsurgical and 12.7% for emergency nonsurgical admission (P < 0.001). CONCLUSIONS: The study demonstrates high mortality rates in patients hospitalised during 1998-2000 for CD, especially in patients over 50. Elective surgery is associated with lower mortality than emergency surgery or medical therapy. Further study is needed to determine whether these patterns have changed following the introduction of biological treatment. PMID- 22070188 TI - Patients treated for psychosis and their perceptions of care in compulsory treatment: basis for an action plan. AB - The purpose of the study was to describe patients' conceptions and experiences of care in compulsory treatment for acute onset of psychosis. Twelve patients with experience of compulsory treatment were interviewed in 2008-2009, and phenomenographic analysis was used to analyse the data. Two descriptive categories emerged in the results: receiving needed support and perceiving respectful care. Patients perceived that coercive interventions were positive if they were given good care, if they were given the shelter they needed, if they got help with understanding and if the setting was healing. Patients felt respected if they were treated like human beings, if they were allowed to retain as much of their autonomy as possible and if they were invited to participate even though they were under compulsory treatment. The results show that it is important to prevent patients from being traumatized during compulsory treatment and to take advantage of patients' inner resources. Patients' experiences of compulsory treatment can form the basis for preparing an individual action plan for future compulsory treatment. Individual action plans could empower patients during compulsory treatment and improve their experience of care. PMID- 22070189 TI - Non-medical prescribing: audit, practice and views. AB - Non-medical prescribing is increasingly utilized in clinical care and UK Standards have been produced for this. This study was undertaken to investigate compliance with these standards which were adopted by one mental health service and to review whether any changes were necessary to existing arrangements monitoring this compliance. A questionnaire was distributed to all 24 non-medical prescribers from one UK Mental Health Trust. Participants were asked to respond to questions about demographic data and prescribing practices. We also asked them to rate their experience on a 5-point scale. In all, 83% of non-medical prescribers responded. The UK Standards were met even though there was a shortfall in the uptake of training and supervision. Non-medical prescribers from the Community Drug Team and Older People's Service prescribed a narrow range of speciality drugs than any other category of drugs, but prescribed more often. UK Standards were met by the majority of non-medical prescribers. However, concerns were noted about a shortfall in training, supervision and experience of some non medical prescribers. Conflict with psychiatrists was reported but their availability for support when necessary was valued. Non-medical prescribers believed that their input with non-medical prescribing had benefited patients. PMID- 22070190 TI - The pH sensor of the plant K+-uptake channel KAT1 is built from a sensory cloud rather than from single key amino acids. AB - The uptake of potassium ions (K+) accompanied by an acidification of the apoplasm is a prerequisite for stomatal opening. The acidification (approximately 2-2.5 pH units) is perceived by voltage-gated inward potassium channels (K(in)) that then can open their pores with lower energy cost. The sensory units for extracellular pH in stomatal K(in) channels are proposed to be histidines exposed to the apoplasm. However, in the Arabidopsis thaliana stomatal K(in) channel KAT1, mutations in the unique histidine exposed to the solvent (His267) do not affect the pH dependency. We demonstrate in the present study that His267 of the KAT1 channel cannot sense pH changes since the neighbouring residue Phe266 shifts its pKa to undetectable values through a cation-pi interaction. Instead, we show that Glu240 placed in the extracellular loop between transmembrane segments S5 and S6 is involved in the extracellular acid activation mechanism. Based on structural models we propose that this region may serve as a molecular link between the pH- and the voltage-sensor. Like Glu240, several other titratable residues could contribute to the pH-sensor of KAT1, interact with each other and even connect such residues far away from the voltage-sensor with the gating machinery of the channel. PMID- 22070191 TI - A meta-analysis of hospital 30-day avoidable readmission rates. AB - RATIONALE AND OBJECTIVES: Urgent readmission to hospital is commonly used to measure hospital quality of care. Hospitals that measure the proportion of urgent readmissions judged avoidable need to know previously published rates for comparison. In this study, we generated a literature-based estimate for the proportion of 30-day urgent readmissions deemed avoidable for hospitals to use to gauge their performance in avoidable readmissions. METHODS: We searched the Medline and Embase databases to identify published studies that reported the proportion of 30-day urgent readmissions deemed avoidable. We then modelled the overall proportion of 30-day urgent readmissions deemed avoidable. RESULTS: We included 16 studies that used a wide variety of patients and a diverse range of methods to classify readmissions as avoidable. Studies reported a broad range for the proportion of urgent 30-day readmissions deemed avoidable. Overall, 848 of 3669 readmissions (23.1%, 95% confidence interval, 21.7-24.5) of 30-day urgent readmissions were classified as avoidable. This proportion varied significantly based on hospital teaching status and number of reviewers for each case [teaching hospitals: with one reviewer, 9.3% (4.2-19.3); with >1 reviewer, 21.6% (13.2 33.3); non-teaching hospital: with one reviewer, 32.2% (11.4-63.9); with >1 reviewer, 39.9% (37.6-42.2)]. Significant heterogeneity remained between studies even after clustering studies by these covariates. CONCLUSIONS: Less than one in four readmissions were deemed avoidable. Health system planners need to use caution in interpreting all cause readmission statistics as they are only partially influenced by quality of care. PMID- 22070192 TI - Histamine pharmacology and new CNS drug targets. AB - During the last decade, the identification of a number of novel drug targets led to the development of promising new compounds which are currently under evaluation for their therapeutic prospective in CNS related disorders. Besides the established pleiotropic regulatory functions in the periphery, the interest in the potential homeostatic role of histamine in the brain was revived following the identification of H(3) and H(4) receptors some years ago. Complementing classical CNS pharmacology, the development of selective histamine receptor agonists, antagonists, and inverse agonists provides the lead for the potential exploitation of the histaminergic system in the treatment of brain pathologies. Although no CNS disease entity has been associated directly to brain histamine dysfunction until now, the H(3) receptor is recognized as a drug target for neuropathic pain, sleep-wake disorders, including narcolepsy, and cognitive impairment associated with attention deficit hyperactivity disorder, schizophrenia, Alzheimer's, or Parkinson's disease, while the first H(3) receptor ligands have already entered phase I-III clinical trials. Interestingly, the localization of the immunomodulatory H(4) receptor in the nervous system exposes attractive perspectives for the therapeutic exploitation of this new drug target in neuroimmunopharmacology. This review focuses on a concise presentation of the current "translational research" approach that exploits the latest advances in histamine pharmacology for the development of beneficial drug targets for the treatment of neuronal disorders, such as neuropathic pain, cognitive, and sleep-wake pathologies. Furthermore, the role of the brain histaminergic system(s) in neuroprotection and neuroimmunology/inflammation remains a challenging research area that is currently under consideration. PMID- 22070193 TI - Local adaptation and matching habitat choice in female barn owls with respect to melanic coloration. AB - Local adaptation is a major mechanism underlying the maintenance of phenotypic variation in spatially heterogeneous environments. In the barn owl (Tyto alba), dark and pale reddish-pheomelanic individuals are adapted to conditions prevailing in northern and southern Europe, respectively. Using a long-term dataset from Central Europe, we report results consistent with the hypothesis that the different pheomelanic phenotypes are adapted to specific local conditions in females, but not in males. Compared to whitish females, reddish females bred in sites surrounded by more arable fields and less forests. Colour dependent habitat choice was apparently beneficial. First, whitish females produced more fledglings when breeding in wooded areas, whereas reddish females when breeding in sites with more arable fields. Second, cross-fostering experiments showed that female nestlings grew wings more rapidly when both their foster and biological mothers were of similar colour. The latter result suggests that mothers should particularly produce daughters in environments that best match their own coloration. Accordingly, whiter females produced fewer daughters in territories with more arable fields. In conclusion, females displaying alternative melanic phenotypes bred in habitats providing them with the highest fitness benefits. Although small in magnitude, matching habitat selection and local adaptation may help maintain variation in pheomelanin coloration in the barn owl. PMID- 22070194 TI - What near misses tell us about risk and safety in mental health care. AB - How service providers and service users view near misses in their daily practice within the rubric of patient safety events is not well understood. Further no studies were located that explored near misses specifically in mental health settings in Canada. In this context, a qualitative study was undertaken to gain insight into how service providers and service users (mental health clients or their family members) experienced and defined near misses. Eight (8) focus groups (n= 88) with service providers and 28 semi-structured interviews with service users were conducted at three mental health care organizations. Content analysis was employed to the dataset that elucidated that near misses were (1) safety threats and vulnerabilities associated with experiencing mental illness; and (2) acts that avert harm and prevent something from happening. Findings are compared to what is currently known about in safety. Implications of findings for practice, research and policy are delineated. PMID- 22070195 TI - PESCADOR, a web-based tool to assist text-mining of biointeractions extracted from PubMed queries. AB - BACKGROUND: Biological function is greatly dependent on the interactions of proteins with other proteins and genes. Abstracts from the biomedical literature stored in the NCBI's PubMed database can be used for the derivation of interactions between genes and proteins by identifying the co-occurrences of their terms. Often, the amount of interactions obtained through such an approach is large and may mix processes occurring in different contexts. Current tools do not allow studying these data with a focus on concepts of relevance to a user, for example, interactions related to a disease or to a biological mechanism such as protein aggregation. RESULTS: To help the concept-oriented exploration of such data we developed PESCADOR, a web tool that extracts a network of interactions from a set of PubMed abstracts given by a user, and allows filtering the interaction network according to user-defined concepts. We illustrate its use in exploring protein aggregation in neurodegenerative disease and in the expansion of pathways associated to colon cancer. CONCLUSIONS: PESCADOR is a platform independent web resource available at: http://cbdm.mdc-berlin.de/tools/pescador/ PMID- 22070196 TI - Visual performance with simultaneous vision multifocal contact lenses. AB - PURPOSE: The aim was to assess visual performance after PureVision high addition multifocal contact lens (PM) fitting through contrast sensitivity measured under different illumination levels for both distance and near. METHODS: In a cross-over study, 20 presbyopic patients were randomly assigned to PM or spectacles. Near contrast sensitivity was measured with the Vistech VCTS 6500 system. Distance contrast sensitivity and distance visual acuity (VA) were measured with the Functional Vision Analyser under photopic (85 cd/m(2) ) and mesopic (3.0 cd/m(2) ) conditions, the latter also under two levels of induced glare: 1.0 lux and 28 lux. Near VA was measured by logMAR charts under approximately 80 cd/m(2) luminance settings. RESULTS: Average monocular spectacle corrected and PM VA were -0.02 +/- 0.05 and 0.03 +/- 0.05 logMAR for distance photopic, 0.16 +/- 0.10 and 0.23 +/- 0.07 logMAR for distance mesopic and -0.03 +/- 0.05 and 0.05 +/- 0.06 logMAR for near photopic, respectively. Average binocular spectacle corrected and PM VA were -0.05 +/- 0.07 and -0.01 +/- 0.03 logMAR for distance photopic, 0.10 +/- 0.06 and 0.18 +/- 0.05 logMAR for distance mesopic and -0.08 +/- 0.06 and 0.02 +/- 0.05 logMAR for near photopic, respectively. Statistically significant differences were found between the contrast sensitivity with the two types of correction for both distance and near, with spectacle correction being better in all cases. CONCLUSION: PureVision multifocal contact lenses preserve good VA and good visual performance under real life conditions. PMID- 22070197 TI - First results from the multicentre study rehabilitation of occupational skin diseases--optimization and quality assurance of inpatient management (ROQ). AB - BACKGROUND AND OBJECTIVES. The German stepwise procedure of handling occupational skin diseases (OSDs) offers interdisciplinary integrated (inpatient/outpatient) rehabilitation measures [tertiary individual prevention (TIP)] for severe OSD. In 2005, a prospective cohort multicentre study was started in order to evaluate TIP. METHODS: One thousand seven hundred and eighty-eight patients with severe OSD were treated and educated in five clinics with follow-up before and 4 weeks after return to work. RESULTS: During the inpatient phase, there was a significant improvement in the severity of OSD (Osnabrueck Hand Eczema Severity Index, p < 0.001) and in the quality of life (Dermatology Life Quality Index, p < 0.001). These effects were largely sustained during the outpatient follow-up phase and in the 4 weeks after return to work. Among all patients, 89.4% used topical steroids before TIP, including 52.5% using high-grade topical steroids; 93.2% of the patients were able to refrain from using topical steroids before returning to work. As a result of TIP, return to work was possible for 1587 patients (88.8%). CONCLUSIONS: The primary objectives of TIP (return to work, improvement of OSD, enhancement of quality of life, and reduction in the use of topical steroids) were successfully met. The long-term follow-up (1 and 3 years after TIP) will examine whether these favourable outcomes can be sustained. PMID- 22070198 TI - The gas phase structure of coulombically stretched polyethylene glycol ions. AB - Prior ion-mobility mass-spectrometry (IMS-MS) studies of polyethylene glycol (PEG) ions have identified only two out of many sharply different observed structures: Linear shapes with several individually solvated singly charged cations at high charge states z (beads on a string), and single multiply charged globules at low z. The present study is devoted to assign all other existing structures of PEG ions, for the first time reaching masses of 100 kDa and charge states up to z = 10. There are at most z different structures at charge state z. All involve a single globule carrying n charges, tied to one or several appendices bearing z - n separate charges in a beads-on-a-string configuration. All sharp shape transitions observed at decreasing ion mass involve ejection of one elementary charge (sometimes two) from the shrinking globule into the growing linear appendage. This picture is supported by molecular dynamics simulations and approximate calculations of electrical mobilities for computed structures. PMID- 22070199 TI - Amyloid peptide regulates calcium homoeostasis and arrhythmogenesis in pulmonary vein cardiomyocytes. AB - BACKGROUND: Amyloid peptides modulate cardiac calcium homoeostasis and play an important role in the pathophysiology of atrial fibrillation. Pulmonary veins (PVs) are critical in the genesis of atrial fibrillation and contain abundant amyloid peptides. Therefore, the purpose of this study is to investigate whether amyloid peptides may change the PV electrical activity through regulating calcium homoeostasis. METHODS AND RESULTS: The channel and calcium-handling protein expressions, intracellular calcium and ionic currents were studied in isolated rabbit PV cardiomyocytes in the presence and absence (control) of beta-amyloid (Abeta(25-35) ) for 4-6 h, using Western blot analysis, indo-1 fluorimetric ratio and whole-cell patch clamp techniques. Abeta(25-35) decreased the expressions of Ca(V) 1.2, total or Ser16-phosphorylated phospholamban (p-PLB), p-PLB/PLB ratio, sodium/calcium exchanger, but did not change ryanodine receptor, sarcoplasmic reticulum (SR) ATPase and K(+) channel proteins (Kir2.1, Kir2.3, Kv1.4, Kv1.5 and Kv4.2). Abeta(25-35) -treated cardiomyocytes had smaller calcium transient, SR calcium store, L-type calcium current and sodium/calcium exchanger current than control cardiomyocytes. Moreover, Abeta(25-35) -treated cardiomyocytes (n = 20) had shorter 90% of the action potential duration (82 +/- 3 vs. 93 +/- 5 ms, P < 0.05) than control cardiomyocytes (n = 16). CONCLUSION: Abeta(25-35) has direct electrophysiological effects on PV cardiomyocytes. PMID- 22070200 TI - New mixed-valent Mn clusters from the use of N,N,N',N'-tetrakis(2 hydroxyethyl)ethylenediamine (edteH4): Mn3, Mn4, Mn6, and Mn10. AB - The syntheses, crystal structures, and magnetochemical characterization are reported for the new mixed-valent Mn clusters [Mn(2)(II)Mn(III)(O(2)CMe)(2)(edteH(2))(2)](ClO(4)) (1), [Mn(II)(2)Mn(III)(2)(edteH(2))(2)(hmp)(2)Cl(2)](Mn(II)Cl(4)) (2), [Mn(III)(6)O(2)(O(2)CBu(t))(6)(edteH)(2)(N(3))(2)] (3), [Na(2)Mn(III)(8)Mn(II)(2)O(4)(OMe)(2)(O(2)CEt)(6)(edte)(2)(N(3))(6)] (4), and (NEt(4))(2)[Mn(8)(III)Mn(2)(II)O(4)(OH)(2)-(O(2)CEt)(6)(edte)(2)(N(3))(6)](5), where edteH(4) is N,N,N',N'-tetrakis-(2-hydroxyethyl)ethylenediamine and hmpH is 2-(hydroxymethyl)pyridine. 1-5 resulted from a systematic exploration of the effect of different Mn sources, carboxylates, the presence of azide, and other conditions, on the Mn/edteH(4) reaction system. The core of 1 consists of a linear Mn(II)Mn(III)Mn(II) unit, whereas that of 2 is a planar Mn(4) rhombus within a [Mn(II)(2)Mn(III)(2)(MU(3)-OR)(2)] incomplete-dicubane unit. The core of 3 comprises a central [Mn(III)(4)(OR)(2)] incomplete-dicubane on either side of which is edge-fused a triangular [Mn(III)(3)(MU(3)-O)] unit. The cores of 4 and 5 are similar and consist of a central [Mn(II)(2)Mn(III)(2)(MU(3)-OR)(2)] incomplete-dicubane on either side of which is edge-fused a distorted [Mn(II)Mn(III)(3)(MU(3)-O)(2)(MU(3)-OR)(2)] cubane unit. Variable-temperature, solid-state direct current (dc) and alternating current (ac) magnetization studies were carried out on 1-5 in the 5.0-300 K range, and they established the complexes to have ground state spin values of S = 3 for 1, S = 9 for 2, and S = 4 for 3. The study of 3 provided an interesting caveat of potential pitfalls from particularly low-lying excited states. For 4 and 5, the ground state is in the S = 0-4 range, but its identification is precluded by a high density of low-lying excited states. PMID- 22070202 TI - Rational synthesis of noncentrosymmetric metal-organic frameworks for second order nonlinear optics. PMID- 22070201 TI - Inhibition of hematopoietic protein tyrosine phosphatase augments and prolongs ERK1/2 and p38 activation. AB - The hematopoietic protein tyrosine phosphatase (HePTP) is implicated in the development of blood cancers through its ability to negatively regulate the mitogen-activated protein kinases (MAPKs) ERK1/2 and p38. Small-molecule modulators of HePTP activity may become valuable in treating hematopoietic malignancies such as T cell acute lymphoblastic leukemia (T-ALL) and acute myelogenous leukemia (AML). Moreover, such compounds will further elucidate the regulation of MAPKs in hematopoietic cells. Although transient activation of MAPKs is crucial for growth and proliferation, prolonged activation of these important signaling molecules induces differentiation, cell cycle arrest, cell senescence, and apoptosis. Specific HePTP inhibitors may promote the latter and thereby may halt the growth of cancer cells. Here, we report the development of a small molecule that augments ERK1/2 and p38 activation in human T cells, specifically by inhibiting HePTP. Structure-activity relationship analysis, in silico docking studies, and mutagenesis experiments reveal how the inhibitor achieves selectivity for HePTP over related phosphatases by interacting with unique amino acid residues in the periphery of the highly conserved catalytic pocket. Importantly, we utilize this compound to show that pharmacological inhibition of HePTP not only augments but also prolongs activation of ERK1/2 and, especially, p38. Moreover, we present similar effects in leukocytes from mice intraperitoneally injected with the inhibitor at doses as low as 3 mg/kg. Our results warrant future studies with this probe compound that may establish HePTP as a new drug target for acute leukemic conditions. PMID- 22070204 TI - Population policy in Western Europe. AB - Abstract Policies concerning procreation and fertility are considered first. In Western Europe there are countries which fully recognize and implement the personal rights of the individual to plan and space the number of children, as well as others denying these rights. The nature and implications of laws and policies concerning contraception, abortion and family planning in general are briefly described and their effects discussed. The second topic considered the welfare and the economy of the family. The incidence of family allowance schemes, taxation systems, protection of working mothers, educational facilities (especially for children of pre-school age), and publicly financed housing is reviewed in an effort to understand whether the various social and legislative systems favour procreation and the raising of the children. The situation is contradictory: very mild pro-natalist effects of family allowances are partly offset by a taxation system that im unfavourable to the family, since husbands' and wives' incomes are in many instances assessed jointly. Increasing protection of working women may reconcile economic activity with childbearing, but serious shortage of institutions to care for very young children makes employment of mothers difficult. The third topic is mobility, internal and international. Possibly the most serious demographic problems of Western Europe are the strong internal streams of migrants, congestion of cities and depopulation of rural areas. Measures for coping with these problems are generally in adequate. At the same time, international migration in very strong with many millions of foreign workers in various countries. The countries of immigration, although themselves tending towards almost stationary populations, seem not to accept the implications of this fact - particularly the cessation of growth of the domestic labour force. Temporary import of manpower through temporary immigration is a short-term solution which cannot be sustained indefinitely. The paper concludes with a final consideration. Western European countries could probably lower their levels of fertility rather easily by giving more support to family planning programmes, liberalizing abortion, etc. But should fertility consistently and for a long time fall below replacement, where are the measures for stimulating recovery? Address delivered before the Population Association of America, New Orleans, 26 April 1973. PMID- 22070203 TI - Effects of heat and ultraviolet radiation on the oxidative stability of pine nut oil supplemented with carnosic acid. AB - The effects of carnosic acid (CA) of different concentrations (0.05, 0.1, and 0.2 mg/g) and two common antioxidants (butylated hydroxytoluene and alpha-tocopherol) on oxidative stability in pine nut oil at different accelerated conditions (heating and ultraviolet radiation) were compared. The investigation focused on the increase in peroxide and conjugated diene values, as well as free fatty acid and thiobarbituric acid-reactive substances. The changes in trans fatty acid and aldehyde compound contents were investigated by Fourier transform infrared spectroscopy, while the changes in pinolenic acid content were monitored by gas chromatography-mass spectrometry. The results show that CA was more effective in restraining pine nut oil oxidation under heating, UV-A and UV-B radiation, in which a dose-response relationship was observed. The antioxidant activity of CA was stronger than that of alpha-tocopherol and butylated hydroxytoluene. Pine nut oil supplemented with 0.2 mg/g CA exhibited favorable antioxidant effects and is preferable for effectively avoiding oxidation. PMID- 22070205 TI - Targets versus extension education: the Family Planning Programme in Uttar Pradesh, India. AB - Abstract The article examines the impact of target setting on a Family Planning Programme in the North Indian State of Uttar Pradesh. The author argues that over concern with target setting has led to a number of negative results including high percentages of marginal cases brought for vasectomy, and low morale on the part of family planning personnel. Trained in extensive education techniques, they have been forced to place quantity above quality once they begin their work out in the districts. The author provides no easy answer to this tension between targets and extension educators, but the problem which he has raised needs consideration in a developing country concerned with implementing an effective programme of population control. PMID- 22070206 TI - Fertility and economic and social development in Turkey: a cross-sectional and time series study. AB - Abstract The paper explores the impact of modernization on the fertility levels in Turkey, which started deliberate efforts at economic, social, and political transformation in the early 1920s. It is a disaggregative study using 'province' as the unit of observation. A relatively consistent series of data on population and various economic and social variables was available with quinquennial censuses starting with the 1940 Census. The technique of reverse projection is used to estimate provincial crude birth rates. Since 1955 there has been a consistent decline in the fertility level. A chain-relationship model is estimated using both cross-sectional and panel data. A major finding of the study is that in Turkey, continuing modernization and the concomitant spread of female education will result in a continuing decline in the fertility rate. This negative influence, stable and substantial over time, is largely due to factors other than the usual association between education and opportunity cost of female employment, such as changing attitudes and tastes. Also with the spread of economic and social development influencing the society's norm for average age at marriage and the proportion of women married, the marital rate, though not so significant as education, imparts a direct depressing effect on the aggregate period fertility rate at any given time. PMID- 22070207 TI - Prospective study of birth interval dynamics in rural Bangladesh. AB - Abstract A group of 209 married, fecund women in rural Bangladesh were studied prospectively for 24 months from 1969 to 1971 to define some of the biological and sociological factors relating to fertility performance. These women were selected from a larger study population of 112,000 that had been followed with a daily house-to-house vital registration programme since 1966. The selected women were interviewed bi-weekly and were asked questions about menstruation, pregnancy, lactation, husband's occupational absences, and monthly urine tests for pregnancy were taken. The results for 193 non-contracepting women revealed that the seasonal pattern of births previously observed in this population could be associated with a corresponding seasonal pattern of conceptions and that this was due to a seasonal trend in fecundability. The highest conception rates were in the coolest months of the year. Post-partum lactational amenorrhoea was very prolonged, averaging 17 months for women with a surviving child. The appearance of the first post-partum menstrual flow (onset of ovulation) also had a seasonal trend which could not be adequately explained. The median waiting time to conception, once menstruation had resumed was eight months. This interval was influenced by seasonal fluctuations, as well as by the age of women and by husbands' absences. The foetal wastage rate was 15.0 per 100 conceptions, with 62 per cent of the foetal losses occurring during the second month of gestation. Overall, the average birth interval was 33 months, with the prolonged lactational amenorrhoea accounting for almost 45 per cent of this interval. From the Department of Population Dynamics, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 21205. PMID- 22070208 TI - Residence background and fertility in Greater Bombay. AB - Abstract The residence background of wives who migrate to metropolitan areas plays an important role in determining their fertility. From the data collected during 1966, relating to 7,872 currently married women of Greater Bombay, an attempt was made to establish differentials in marital fertility by residence background of the wives. This was categorized into three groups - non-migrants, urban migrants and rural migrants. It was observed that rural migrant wives exhibited significantly higher fertility compared with the other two groups, and this was explained by their lower educational attainment. Between the non-migrant and the urban migrant wives the latter consistently showed lower fertility for all age groups up to 40, while there was a reversal in the age group 40 and above, where non-migrants exhibited lower fertility. The urban migrant wives showed a somewhat higher level of education, most likely on account of selectivity, compared to the non-migrants. However, presence of a sizeable number of Parsee wives, characterized by a distinct urban culture and considerably lower fertility, was largely responsible for the low fertility of the non-migrant wives in the age group 40 and above. The variable that has emerged as the most influential in creating fertility differentials is education of the wife, which is shown to be negatively associated with the level of fertility. Wife's education explains to a large extent the observed fertility differentials by residence background. PMID- 22070209 TI - Some demographic consequences of changing cohort fertility patterns: An investigation using the Gompertz function. AB - Abstract In this paper are formulated some convenient summary measures of fertility patterns. These measures, which are based on the Gompertz function, are total lifetime fertility, median age of mothers at childbirth, and inter-quartile range of age of mothers at childbirth. Estimates of the parameters of Gompertz function, based on Canadian data, are used to derive, for each of the summary measures, values which reflect historical fertility experience, and thus give an impression about the range of realistic values for these measures. A simple model of demographic activity which includes the Gompertz function is also considered, and this model is used in computer simulation experiments to determine the macro demographic effects of changes in each of the three summary measures. PMID- 22070210 TI - A comment on Schnaiberg's measure of fertility and child dependency. AB - Abstract This comment discusses some potential difficulties in the construction and use of a new fertility variable proposed in a recent issue of Population Studies, and considers one possible remedy. PMID- 22070213 TI - Prenatal high-dose immunoglobulin treatment for neonatal hemochromatosis: a case report and review of the literature. AB - Neonatal hemochromatosis is a difficult disorder to cure, and it has a high rate of recurrence. High-dose immunoglobulin treatment is very effective as prenatal treatment for recurrent neonatal hemochromatosis. A 34-year-old pregnant Japanese woman underwent high-dose immunoglobulin treatment for recurrent neonatal hemochromatosis. High-dose non-specific intravenous immunoglobulin (1 g/kg bodyweight) was administered to the mother intravenously every week from 18 until 36 gestational weeks. A male infant was delivered at 37 weeks of gestation, and his condition was favorable, including hepatic function. The use of gamma globulin for neonatal hemochromatosis appears adequately validated by experience. PMID- 22070214 TI - The relevance of accurate comprehensive treatment parameters in photobiomodulation. PMID- 22070215 TI - A systematic review of the cost and cost effectiveness of treatment for multidrug resistant tuberculosis. AB - BACKGROUND: Around 0.4 million cases of multidrug-resistant tuberculosis (MDR-TB) occur each year. Only a small fraction of these cases are treated according to international guidelines. Evidence relevant to decisions about whether to scale up treatment for MDR-TB includes cost and cost-effectiveness data. Up to 2010, no systematic review of this evidence has been available. OBJECTIVE: Our objective was to conduct a systematic review of the cost and cost effectiveness of treatment for MDR-TB and synthesize the available data. METHODS: We searched for papers published or prepared for publication in peer-review journals and grey literature using search terms in five languages: English, French, Portuguese, Russian and Spanish. From an initial set of 420 studies, four were included, from Peru, the Philippines, Estonia and Tomsk Oblast in the Russian Federation. Results on costs, effectiveness and cost effectiveness were extracted. Assessment of the quality of each economic evaluation was guided by two existing checklists around which there is broad consensus. Costs were adjusted to a common year of value (2005) to remove distortions caused by inflation, and calculated in two common currencies: $US and international dollars (I$), to standardize for purchasing power parity. Data from the four identified studies were then synthesized using probabilistic sensitivity analysis, to appraise the likely cost and cost effectiveness of MDR-TB treatment in other settings, relative to WHO benchmarks for assessing whether or not an intervention is cost effective. Best estimates are provided as means, with 5th and 95th percentiles of the distributions. RESULTS: The cost per patient for MDR-TB treatment in Estonia, Peru, the Philippines and Tomsk was $US10 880, $US2423, $US3613 and $US14 657, respectively. Best estimates of the cost per disability-adjusted life-year (DALY) averted were $US598 (I$960), $US163 (I$291), $US143 (I$255) and $US745 (I$1059), respectively. The main influences on costs were (i) the model of care chosen (the extent to which hospitalization or ambulatory care were relied upon) and (ii) the second-line drugs included in the treatment regimen. When extrapolated to other settings, the best estimate of the cost of treatment varied from US3401 to US195 078, depending on the region and model of care. The cost per DALY averted was lower than GDP per capita in all 14 WHO sub-regions considered, with better cost effectiveness for outpatient versus inpatient models of care. CONCLUSIONS: Treatment for MDR-TB can be cost effective in low- and middle-income countries. Evidence about the relative cost effectiveness of outpatient versus inpatient models of care is limited and more data are needed from Africa and Asia- especially India and China, which have the largest number of cases. Unless there is strong evidence that hospitalization is necessary to achieve high rates of adherence to treatment, patients with MDR-TB should be treated using mainly ambulatory care. PMID- 22070216 TI - Bimolecular reaction via the successive introduction of two substrates into the crystals of networked molecular cages. AB - Two substrates, 4-hydroxydiphenylamine (3) and ethyl isocyanate (4), were successively introduced into the crystals of networked M(6)L(4) cages 1. Because of the encapsulation effect, most of the initially introduced substrate 3 remained within the crystals during immersion in a solution of 4. X-ray analysis revealed that before the reaction, the nucleophilic NH group of 3 is effectively protected by tight packing within the cage units while the OH group is exposed to the incoming second substrate. Successive introduction of 4 into the crystal results in the chemoselective acylation of 3 at the less nucleophilic OH group. The observed chemoselectivity is consistent with that exhibited by discrete M(6)L(4) cage 2 in solution. PMID- 22070217 TI - Postweaning mulstisystemic wasting syndrome (PMWS) in pigs and porcine circovirus (PCV). An indexed bibliography. AB - Summary This bibliography contains the bibliographic data, including the abstracts (if available), the post addresses and as far as available also the E mail addresses of the authors, of 177 articles on postweaning multisystemic wasting syndrome (PMWS) in pigs and porcine circovirus (PCV). The bibliography concerns the period 1982-2002. The vast majority of the articles (151 of 177 being 85%) were published in the period 1998-2002. All publications except one are taken from easily accessible journals. The exception concerns reference 52 being the first report on PMWS, which has been published in a congress proceedings. To improve the accessibility of the bibliography five indices are given referring to the authors, the subjects, the serials, the years of publication and the countries. PMID- 22070219 TI - Muscarinic receptors: their roles in disorders of the central nervous system and potential as therapeutic targets. AB - Phylogenetically, acetylcholine is an ancient neurochemical. Therefore, it is not surprising that cholinergic neurons project extensively throughout the central nervous system, innervating a wide range of structures within the brain. In fact, acetylcholine is involved in processes that underpin some of our most basic central functions. Both muscarinic and nicotinic receptor families, which mediate cholinergic transmission, have been implicated in the pathophysiology of psychiatric and neurological disorders. The question that remains to be definitively answered is whether or not these receptors are viable targets for the development of future therapeutic agents. PMID- 22070220 TI - Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromso Study. AB - BACKGROUND: Laboratory reference intervals are not necessarily reflecting the range in the background population. This study compared creatine kinase (CK) reference intervals calculated from a large sample from a Norwegian population with those elaborated by the Nordic Reference Interval Project (NORIP). It also assessed the pattern of CK-normalization after standardized control analyses. METHODS: New upper reference limits (URL) CK values were calculated after exclusion of individuals with risk of hyperCKemia and including individuals with incidentally detected hyperCKemia after they had completed a standardized control analysis. After exclusion of 5924 individuals with possible causes of hyperCKemia, CK samples were analyzed in 6904 individuals participating in the 6th survey of The Tromso Study. URL was defined as the 97.5 percentile. RESULTS: New URL in women was 207 U/L. In men <50 years it was 395 U/L and in men >=50 years 340 U/L. In individuals with elevated CK, normalization grade after control analysis was inversely correlated to the CK level (p<0.04). CONCLUSIONS: URL CK values in women and in men <50 years of age were in accordance with URL CK values given by the NORIP. In men >=50 years, a higher URL was found and the findings suggest an upward adjustment of URL in this age group. PMID- 22070221 TI - Development of control material for hemoglobin analysis. AB - Background: There is no certified control material for hemoglobin analysis which has the hemoglobin (Hb)A(2)/E level as high as found in ?-thalassemia trait, HbE trait, ?-thalassemia/HbE disease and homozygote of HbE, the thalassemia types found frequently in the Southeast Asian population. The aim of this study was to prepare the lyophilized hemoglobin control materials for hemoglobin analysis. Methods: Washed and dialysed erythrocytes of normal individuals and patients with ?-thalassemia trait, HbE trait, ?-thalassemia/HbE disease, homozygous HbE were lysed in 5% sucrose solution. The lyophilized hemoglobin control materials were prepared by using a freeze-drying (lyophilization) method. The high performance liquid chromatography (HPLC) analysis of lyophilized hemoglobin was performed after storing at ?20?C for 1, 15 and 30?days and for 3?months. Results: The chromatograms of lyophilized hemoglobin control materials showed similar patterns and similar levels of HbA, HbA(2)/E and HbF when compared with equivalent fresh whole blood. Moreover, the lyophilized hemoglobin presented a good correlation coefficient (r>0.990) of relationships between HPLC, low pressure liquid chromatography (LPLC) and capillary electrophoresis (CE) methods. Conclusions: The lyophilized hemoglobin could be developed and used as control materials for hemoglobin analysis. PMID- 22070222 TI - The multi-cancer marker, rs6983267, located at region 3 of chromosome 8q24, is associated with prostate cancer in Greek patients but does not contribute to the aggressiveness of the disease. AB - BACKGROUND: Recently, several polymorphisms located on human chromosome 8q24 were found to be associated with prostate cancer risk with different frequency and incidence among the investigated populations. The authors conducted a prostate cancer case-control study in the Greek population to evaluate the association of the single nucleotide polymorphism (SNP) rs6983267, located at region 3 of chromosome 8q24, with this type of cancer. METHODS: Samples of total blood from 86 patients with histologically confirmed prostate cancer and 99 healthy individuals were genotyped using real time polymerase chain reaction (PCR). Tumor node-metastasis (TNM) stage, Gleason score and levels of prostate-specific antigen (PSA) at diagnosis were included in the analysis. RESULTS: A highly significant association (odds ratio=2.84 and p-value=0.002) was found between rs6983267 and prostate cancer in the Greek population. The sensitivity, specificity, negative and positive predictive values of the presence of G allele for the discrimination between patients and controls were 81.40%, 39.4%, 53.9% and 70.9%, respectively. A lower proportion of homozygotes was found in patients with PSA level <4 ng/mL compared to those with PSA level more than 4 ng/mL (p=0.019). None of the other clinical factors nor the aggressiveness of the disease were found to be significantly associated with rs6983267 genotype. CONCLUSIONS: The SNP rs6983267 is an established marker for a range of cancers. In prostate cancer, it indicates an enhanced risk for carriers to develop the disease in general. In our study it showed no association with aggressive forms or familial and early-onset prostate cancer families. PMID- 22070223 TI - Interference of hemoglobin (Hb) Las Palmas with HPLC measurement of HbA(1c) in 87 patients. PMID- 22070224 TI - Victimization in individuals suffering from psychosis: a Swedish cross-sectional study. AB - The aims of the study were to investigate: (1) self-reported adulthood and last year victimization in male and female outpatients suffering from psychosis; (2) relationships to perpetrators; (3) whether drugs or alcohol were involved in victimization situations; (4) places where victimization occurred. Patients were randomly selected from five outpatient units geared to patients with psychosis; 174 patients participated in a structured face-to-face interview. Experiences of victimization in adulthood were reported by 67%, 33% in the previous year. During adulthood 51% had been physically and 32% sexually victimized and 39% threatened. In the previous year 21% reported threats, 20% physical and 15% sexual victimization. Women reported greater exposure to physical and sexual victimization than men during adulthood and in the previous year. Strangers and acquaintances were mainly reported as perpetrators and half (55%) of those victimized in the previous year stated no involvement of alcohol or drugs. Victimization mainly occurred in the patients' own home (59%), outside downtown (34%), or in others homes (38%). The results of this study give reason to highlight the importance for research and clinical practices to adopt a broad frame of interpretation concerning victimization in patients, covering both individual and environmental factors. PMID- 22070225 TI - Role of the hypothalamus in the neuroendocrine regulation of body weight and composition during energy deficit. AB - Energy deficit in lean or obese animals or humans stimulates appetite, reduces energy expenditure and possibly also decreases physical activity, thereby contributing to weight regain. Often overlooked in weight loss trials for obesity, however, is the effect of energy restriction on neuroendocrine status. Negative energy balance in lean animals and humans consistently inhibits activity of the hypothalamo-pituitary-thyroid, -gonadotropic and -somatotropic axes (or reduces circulating insulin-like growth factor-1 levels), while concomitantly activating the hypothalamo-pituitary-adrenal axis, with emerging evidence of similar changes in overweight and obese people during lifestyle interventions for weight loss. These neuroendocrine changes, which animal studies show may result in part from hypothalamic actions of orexigenic (e.g. neuropeptide Y, agouti related peptide) and anorexigenic peptides (e.g. alpha-melanocyte-stimulating hormone, and cocaine and amphetamine-related transcript), can adversely affect body composition by promoting the accumulation of adipose tissue (particularly central adiposity) and stimulating the loss of lean body mass and bone. As such, current efforts to maximize loss of excess body fat in obese people may inadvertently be promoting long-term complications such as central obesity and associated health risks, as well as sarcopenia and osteoporosis. Future weight loss trials would benefit from assessment of the effects on body composition and key hormonal regulators of body composition using sensitive techniques. PMID- 22070226 TI - Weight gain and lipid-glucose profiles among patients taking antipsychotic medications: comparisons for prescriptions administered using algorithms versus usual care. AB - The purpose of this study was to determine if treatment strategy had a significant effect on the occurrence of physiological changes consistent with metabolic syndrome and/or type 2 diabetes in patients using atypical antipsychotic medications. The four variables assessed were: weight gain, fasting blood sugar, triglycerides and cholesterol. The two strategies compared were (1) evidence-based practice, derived from the Texas Medication Algorithm Project, and (2) practitioner preference. A retrospective chart review was performed on patients diagnosed with a chronic psychiatric disorder being treated with atypical antipsychotics. The dates of the reviewed records were from 1 January 2008 to 31 December 2008. The sample of patients totaled 113. Statistical analysis included logistic regression for each of the four variables assessed. The use of evidence-based practice guidelines was found to have strong positive effects on two of the four variables assessed. Further studies need to be conducted to include medications being taken to lower lipids and blood sugar. Overall, the use of evidence-based practice guidelines has a positive effect on weight, triglycerides and cholesterol. It is important that patients be closely monitored and changes made in a timely manner to minimize adverse effects of atypical antipsychotics. PMID- 22070227 TI - Recruitment of the endosomal WASH complex is mediated by the extended 'tail' of Fam21 binding to the retromer protein Vps35. AB - The retromer complex is a conserved endosomal protein sorting complex that sorts membrane proteins into nascent endosomal tubules. The recognition of membrane proteins is mediated by the cargo-selective retromer complex, a stable trimer of the Vps35 (vacuolar protein sorting 35), Vps29 and Vps26 proteins. We have recently reported that the cargo-selective retromer complex associates with the WASH (Wiskott-Aldrich syndrome homologue) complex, a multimeric protein complex that regulates tubule dynamics at endosomes. In the present study, we show that the retromer-WASH complex interaction occurs through the long unstructured 'tail' domain of the WASH complex-Fam21 protein binding to Vps35, an interaction that is necessary and sufficient to target the WASH complex to endosomes. The Fam21-tail also binds to FKBP15 (FK506-binding protein 15), a protein associated with ulcerative colitis, to mediate the membrane association of FKBP15. Elevated Fam21 tail expression inhibits the association of the WASH complex with retromer, resulting in increased cytoplasmic WASH complex. Additionally, overexpression of the Fam21-tail results in cell-spreading defects, implicating the activity of the WASH complex in regulating the mobilization of membrane into the endosome-to-cell surface pathway. PMID- 22070229 TI - Assessing the problem of counterfeit medications in the United Kingdom. AB - Counterfeit medicines pose an ever-increasing threat to public health, although precise tracking of illegal counterfeit prescription drug activity is difficult. Available data indicate that all types of medications have been targeted. Adverse health effects, including death, have resulted from using counterfeit medications; consumers who self-medicate without appropriate interactions with the healthcare system rarely receive adequate healthcare. The Internet provides a large, convenient route for counterfeiters to reach potential buyers with unregulated, often dangerous, products. The majority of medicines purchased via unverified Internet sites are counterfeit; often, these products lack the purported drug compound or have variable concentrations of active ingredients and sometimes contain dangerous toxins. Although many consumers acknowledge some degree of risk with purchasing medications via the Internet, speed, convenience and cost often prompt these purchases. Counterfeit medications also have been detected in the legitimate supply chain, but represent a significantly smaller proportion of sales than those purchased via the Internet. Pilot programmes in Europe have demonstrated that product verification systems prevent penetration of counterfeit products into the legitimate supply chain. Significant EU legislation, including stronger penalties for counterfeiting, is in development. In the United Kingdom, the Medicines and Healthcare Products Regulatory Agency (MHRA) launched an initiative against counterfeit medication. Healthcare professionals should report suspected cases of counterfeit medication to the MHRA, be alert to threats to the medicine supply, and provide practical advice to patients about ordering medications online, including avoiding unregulated Internet pharmacies, and being suspicious of sites offering substantial discounts and prescription-only medication without a prescription. PMID- 22070228 TI - Successful combined therapy with tamoxifen and lithium in a paradoxical sleep deprivation-induced mania model. AB - BACKGROUND: Previous studies have suggested that manic states and sleep deprivation could contribute to the pathophysiology of bipolar disorder (BD) through protein kinase C (PKC) signaling abnormalities. Moreover, adjunctive therapy has become a standard strategy in the management of BD patients who respond poorly to current pharmacological treatments. AIM: Thus, the aim of this study was to investigate the possible involvement of PKC inhibition by tamoxifen both separately or in combination with lithium, in paradoxical sleep deprivation (PSD)-induced hyperactivity, one facet of mania-like behavior. MATERIALS & METHODS: Adult male C57BL/6J mice were randomly distributed (n = 7/group) in 24-h PSD or control groups and injected intraperitoneally (i.p.) with vehicle, lithium (50, 100, or 150 mg/kg) or tamoxifen (0.5, 1.0, or 2.0 mg/kg - experiment 1). In a second experiment, mice were injected i.p. with vehicle or a combination of subeffective doses of lithium and tamoxifen. Animals were subjected to a protocol based on repetitive PSD conditions, followed by assessment of locomotion activity in the open-field task. RESULTS: PSD significantly increased locomotor activity in both experiments. These behavioral changes were prevented by a treatment with lithium or tamoxifen, or a combined treatment with both lithium and tamoxifen. DISCUSSION: Therefore, our findings suggest that lithium and tamoxifen exert reversal effects against PSD-induced hyperactivity in mice. CONCLUSION: Furthermore, tamoxifen as an adjunct to lithium therapy provides support for an alternative treatment of individuals who either do not respond adequately or cannot tolerate the adverse effects associated with therapeutic doses of lithium. PMID- 22070230 TI - Total synthesis of (-)-virginiamycin M2: application of crotylsilanes accessed by enantioselective Rh(II) or Cu(I) promoted carbenoid Si-H insertion. AB - A stereoselective synthesis of the antibiotic (-)-virginiamycin M(2) is detailed. A convergent strategy was utilized that proceeded in 10 steps (longest linear sequence) from enantioenriched silane (S)-15. This reagent, which was prepared via a Rh(II)- or Cu(I)-catalyzed carbenoid Si-H insertion, was used to introduce the desired olefin geometry and stereocenters of the C1-C5 propionate subunit. A modified Negishi cross-coupling or an efficient alkoxide-directed titanium mediated alkyne-alkyne reductive coupling strategy was utilized to assemble the trisubstituted (E,E)-diene. An underutilized late-stage SmI(2)-mediated macrocyclization was employed to construct the 23-membered macrocycle scaffold of the natural product. PMID- 22070231 TI - Detection and widespread distribution of sodium channel alleles characteristic of insecticide resistance in Culex pipiens complex mosquitoes in China. AB - Culex pipiens complex mosquitoes are widely distributed throughout China and are known to be important disease vectors. Two pyrethroid resistance associated mutations have been identified in Cx. pipiens complex (Diptera: Culicidae), but there is little information on the diversity and distribution of kdr alleles in pyrethroid resistance in Cx. pipiens complex mosquitoes in China. In the present study, we report on a modified three tube allele-specific (AS)-PCR method for detecting the 1014F and 1014S alleles. The new technique was applied to identify the distribution of the two alleles in natural Cx. pipiens complex populations in China. The results confirmed that the new method is both sensitive and specific. The 1014F allele was found in all 14 of the field populations tested (frequency ranged from 6.8 to 76.2%) and the 1014S allele was found in almost two-thirds (frequency from 2.4 to 28.6%), indicating that the genotypes known to be associated with pyrethroid resistance are widespread in China. The resistance associated alleles were more common in southern Chinese sampling sites than in northern sites. The coexistence of the two resistant mutations in individual mosquitoes was also observed in five of the field populations. Two alternative mutations within the L1014 codon were identified in Culex pipiens molestus Forskal, 1775, including a non-synonymous mutation resulting in a 1014C substitution. PMID- 22070232 TI - Speciation within genomic networks: a case study based on Steatocranus cichlids of the lower Congo rapids. AB - Hybridization in animals is a much more common phenomenon as previously thought and may have profound implications for speciation research. The cichlid genus Steatocranus (Teleostei: Cichlidae), a close relative to members of the East African cichlid radiations, radiated under riverine conditions in the lower Congo rapids and produced a small species flock. Previous phylogenetic analyses suggested that hybridization occurred and contributed to speciation in this genus. A re-analysis of an already published 2000 loci-AFLP data set explicitly testing for patterns of ancient gene flow provided strong evidence for a highly reticulate phylogenetic history of the genus. We provide, to our knowledge, the first example of a complex reticulate network in vertebrates, including multiple closely related species connected through ancient as well as recent gene flow. In this context, the limited validity of strictly bifurcating tree hypotheses as a phylogenetic basis for hypothesis testing in evolutionary biology is discussed. PMID- 22070234 TI - The economic rationality of high fertility: An investigation illustrated with Nigerian survey data. AB - Summary In much of the developing world, especially among rural populations who usually are the majority, field researchers find that fertility is high and fairly stable and that there is little evidence either that high-fertility parents are relatively economically disadvantaged or that they believe themselves to be so. On the other hand most of modern economic-demographic theory suggests that the members of large families should be worse off than the members of small families. It is argued that the 'hardest' data are those of high fertility and the relative well being of large families and that the proper social scientific approach should have been to base further investigation upon such findings. It is suggested that much of the economic theorizing has erred because of bad survey data and ethnocentric bias in the research. Data are analysed from research programmes in Ghana and Nigeria to show that high fertility is not as disadvantageous as is often suggested. The main source of evidence is Project 2 of the Nigerian segment of the Changing African Family Project, a 1973 sample survey of 1,499 females and 1,497 males, Yoruba and over 17 years of age, in the Western and Lagos States of Nigeria. It is concluded that the economic ends of a society are largely determined by its social ends and that the economic rationality of high fertility can be determined only within the context of a society's structure and ends. There can be no such thing as a purely economic theory of fertility. It is also concluded that the society studied is moving towards a condition where high fertility will be increasingly disadvantageous and that this is being brought about more by Westernization than modernization. PMID- 22070233 TI - Metal-organic framework materials as chemical sensors. PMID- 22070235 TI - Fertility levels and trends in Indonesia. AB - Summary Fertility estimates from the 1973 Indonesian Fertility Mortality Survey are presented and compared with estimates from the 1971 population census. Although there are some differences, on the whole the two sources are remarkably consistent, indicating the same regional differentials: highest fertility in Sumatra (T.F.R. in rural areas around 7.0), followed by West Java and Sulawesi, Bali, then Central and East Java (T.F.R. in rural areas around 50). Coale's Index of Overall Fertility (If) is 39 per cent higher in rural Sumatra than in rural East Java. Fertility in urban areas is somewhat below rural fertility in all regions. The age pattern of fertility in Sumatra, Sulawesi and West Java is consistent with Henry's notion of 'natural fertility', and indeed the survey data show these regions to be almost innocent of deliberate practice of contraception. The lower fertility levels in Central and East Java appear to be related to patterns of extended lactation and post-partum abstinence, though modern contraception promoted by the national family planning programme is also on the increase. Though lower than elsewhere, both actual fertility and stated ideal family size in Central and East Java are well above the levels needed to achieve replacement levels of fertility. PMID- 22070236 TI - The relation of economic class and fertility: An analysis of some Indonesian data. AB - Summary Many recent fertility studies in developing societies put forward the hypothesis of a negative relation between economic class and fertility. Data showing a positive relationship are frequently dismissed a priori as resulting from the reporting errors of illiterate women. This study draws on data from Indonesia's 1971 Census, a 1973 sample survey of fertility and mortality, and an intensive community study in Java, to argue that an observed positive relation between class and fertility is real, and is related to differences in patterns of marital disruption, postpartum abstinence, and fecundity. The positive relation may be reversed in the future as changes in these patterns, and the impact of the national family planning programme, affect the family structure of each class differently. Had the positive relation in this context been attributed offhand to reporting errors, these important socio-economic changes would have been misunderstood, and possibly ignored. PMID- 22070237 TI - A dynamic model of the reproductive process. AB - Summary A dynamic deterministic model of the reproductive process is presented. The model describes and analyses the effect of intermediate fertility variables on fertility. The intermediate fertility variables which are the inputs to the model, include the duration of post-partum amenorrhea, fecundability, incidence of spontaneous and induced abortion, contraceptive use and effectiveness, the distribution of age at first marriage and the age specific risks of marital disruption and remarriage. To test the validity of this model, it is fitted to data obtained from reproductive histories of 512 marriages occurring during the first half of the eighteenth century in Canada. PMID- 22070238 TI - Estimating adult mortality levels from information on widowhood. AB - Summary A range of indirect techniques has been developed for mortality estimation in societies lacking adequate vital registration records. Information on orphanhood has been widely used as an estimator of adult mortality, with generally plausible results. Doubts have remained, however, about potential biases, and the method is less satisfactory for the estimation of male mortality. Information on widowhood, or more strictly the survival of first spouse, has several possible advantages over information on orphanhood. Model first marriage functions and model life tables are used to calculate proportions widowed of first spouse, for both females and males, by marital duration and by age. These proportions widowed are then related to life table survivorship probabilities to provide weighting factors for the conversion of observed proportions widowed into estimates of survivorship probabilities. The application of the method is illustrated with data collected by the 1974 post-enumeration survey of Bangladesh, with apparently encouraging results. PMID- 22070239 TI - Patterns underlying fertility schedules: A decomposition by both age and marriage duration. AB - Summary Model fertility schedules based on the proportions married and the age pattern of marital fertility are unsatisfactory to the extent that marital fertility does not depend on age alone but also on other factors. Most notably, models based just on age fail to allow for differences between populations in their composition by marriage duration. Examination of the major series of fertility rates specific by both age and duration of marriage (Sweden 1911-70, England and Wales, 1941-70) reveals striking underlying regularities. The marital fertility rates observed at any given point in time can be factored into three independent components - an overall level, a vector of age effects common to all marriage durations and a vector of duration effects common to all age groups. A simple product of these three components is shown to approximate the data very closely over the entire series, despite major changes in the aggregate levels of fertility and nuptiality during the periods concerned. Not only are the data tightly structured, conforming very closely to this simple multiplicative model, but the vectors of age and duration effects themselves are shown to exhibit clear and meaningful regularities. PMID- 22070240 TI - The estimation of adult mortality in Africa from data on orphanhood. AB - Summary Until recently, very little information has been available about the levels and patterns of adult mortality in tropical Africa, but during the past decade several countries have included questions in censuses and surveys as to whether a person's father and mother are still alive. From the data so obtained, estimates of adult mortality have been prepared. This paper compares the results of three such exercises with alternative estimates of adult mortality derived from other sources. In the case of Chad, the orphanhood data obtained in the demographic sample survey of 1964 yielded estimates of mortality which agreed reasonably closely with those obtained from questions on deaths of household members occurring during the twelve months preceding the survey. The latter data however were themselves subject to substantial errors and had to be corrected using techniques based on stable population theory. For Kenya, the orphanhood questions were included in the 1969 census and the results were compared with the mortality estimates derived from inter-censal survival from 1962 to 1969. Once again, the data obtained from the latter were subject to error but in general appeared to be consistent with the orphanhood estimates. The third comparison was made from Malawi, where alternative mortality figures were available from the Malawi Population Change survey which was a 'dual record' type of operation, conducted in 1971/2. The agreement in this case was remarkably close, once the number of deaths had been corrected for omissions by both systems with allowance for positive correlation. It is concluded that as a simple and inexpensive technique of estimating adult mortality, the orphanhood approach has much to recommend it. PMID- 22070241 TI - Changes in childlessness in the United States: A demographic path analysis. AB - Summary This paper describes changes in the incidence of marital childlessness among United States women since 1940 and tests a model to explain recent observed trends toward increasing childlessness. Based on U.S. Bureau of the Census sources, data are presented that indicate a substantial increase in childlessness for married women under 30 years of age since 1960. A path model is developed based on previous research on childlessness, in an attempt to explain this change. The model is composed of 1960-70 changes in (1) mean age at first marriage, (2) mean educational attainment, (3) the proportion of women in the labour force, (4) the proportion of women enrolled as students, (5) the incidence of marital disruption, and (6) the proportion of women living in urban environments. Using quarter-year age cohort data derived from the 1960 and 1970 1/100 Public Use Samples the results indicate that a substantial part of the increase in childlessness csn be explained by this model. Particularly important were increased enrolment of married women in education, labour force participation, and mean age of first marriage. The results suggest the relevance of structural changes along with birth expectation attitudes in predicting trends in childlessness in the United States. PMID- 22070242 TI - Problems of abortion in Britain - Aberdeen, a case study. AB - Summary This paper reports on nearly all pregnancies occurring in the City of Aberdeen in the years 1961-74 (births, and therapeutic and spontaneous abortions) and on male and female sterilization and the use of contraception. The collection of these data for a defined community was made possible through the coordinated and comprehensive maternity and contraceptive services. Several important innovations made during the years included the introduction of oral contraception and the inter-uterine device, laparoscopic sterilization and vasectomy. The Abortion Act 1969 came into force and at different times the Local Authority Family Planning Clinic made many changes including the removal of charges and of the need for referral. The pattern of outcome differs for legitimate and illegitimate pregnancies, which are considered separately. Over half of all first pregnancies now occur before marriage and their outcome in women in different occupational groups is discussed. Oral contraception is favoured for postponing or spacing pregnancies, but when it comes to limitation of family size, couples have increasingly requested sterilization. Nevertheless there has been a ten-fold increase in the proportion of pregnancies being terminated. Aberdeen's birth rate is now below replacement level but the real objective 'every pregnancy a wanted pregnancy' is far from being achieved in either married or unmarried women. PMID- 22070243 TI - Female status among soviet central Asian nationalities: The melding of Islam and Marxism and its implications for population increase. AB - Summary Marxist ideology has emphasized the rights of women to a degree perhaps unparalleled among political movements, whereas Islamic ideology has confined women to the traditional role of wife and mother. In Soviet Central Asia these two ideologies have clashed for more than 50 years. Data from the 1959 and 1970 censuses of the U.S.S.R. are used to show three aspects of the position of Soviet women of Islamic nationality as compared with the position of Soviet women of non Islamic nationality, namely, educational attainment relative to men, non agricultural labour force participation relative to men, and the burden of child dependency. The hypothesis is put forward that the status of women among Soviet Islamic nationalities should be lower than among Soviet non-Islamic nationalities, but that the difference between the two groups in the various aspects of female status should diminish over time. The position of women among the Soviet Islamic nationalities was also compared with that of women in various Islamic nations with the hypothesis that female status should be higher among the former than the latter. The predictions were upheld, with the notable exception of two of the three pedictions concerning the burden of child dependency occasioned by the finding that child dependency increased substantially, from 1959 to 1970 for Islamic nationalities but not for non-Islamic, and by 1970 was higher for Soviet Islamic nationalities than for the Islamic nations of the Middle East and North Africa. Several possible explanations are advanced for the above-mentioned unpredicted findings. PMID- 22070244 TI - Comments on Daniel A. Seiver's 'Recent fertility in Mexico: Measurement and Interpretation.'. AB - Abstract In a recent article in this Journal,(1)Daniel A. Seiver concludes that 'fertility' in Mexico did not decline between 1960 and 1970. His conclusion is based primarily on an increase in the child-woman ratio from 725 per 1,000 in 1960 to 762 in 1970. Seiver simply asserts that this increase cannot be completely explained by declining infant mortality and under-enumeration. (2) . (3). PMID- 22070245 TI - A reply to W. Hicks's comments. AB - Abstract W. Whitney Hicks's comments on my paper(1) can be reduced to four major points, all of which I dispute wholeheartedly: PMID- 22070248 TI - Urinary liver-type fatty acid-binding protein level as a predictive biomarker of contrast-induced acute kidney injury. AB - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a well-known complication of contrast medium exposure in patients with chronic kidney disease. However, there are no biological markers to accurately predict the onset of CI AKI. Liver-type fatty acid-binding protein (L-FABP), an intracellular carrier protein for free fatty acids, is markedly upregulated and abundantly expressed in the proximal tubules after renal ischaemia. We prospectively investigated whether urinary L-FABP is a suitable marker for the prediction of CI-AKI. METHODS: We performed a prospective study of 220 consecutive patients with chronic kidney disease who underwent elective catheterization [serum creatinine (Cr) >= 1.2 mg/dL (106 M)]. Serum Cr and L-FABP levels were measured immediately before and 1 and 2 days after the procedure. CI-AKI was defined as an increase in serum Cr level of >= 0.3 mg/dL within 48 h after the procedure. RESULTS: We observed the development of CI-AKI in 19 patients (8.6%). Urinary L-FABP levels were significantly higher in patients with CI-AKI than those without CI-AKI before contrast medium exposure. Receiver operating characteristic analysis showed that baseline urinary L-FABP level exhibited 82% sensitivity and 69% specificity, at a cut-off value of 24.5 MUg/g Cr. Using multivariate analysis, we found that independent predictors of CI-AKI development were L-FABP level of >= 24.5 MUg/g Cr [odds ratio (OR): 9.10; 95% confidence interval (CI), 3.20-28.9], and left ventricular ejection fraction <= 40% (OR, 3.42; 95% CI, 1.07-10.8). CONCLUSIONS: Urinary L-FABP level is useful for predicting the onset of CI-AKI before contrast medium exposure. PMID- 22070250 TI - Achieving coherent policies for conservation and sustainable use of marine ecosystems. PMID- 22070249 TI - clusterMaker: a multi-algorithm clustering plugin for Cytoscape. AB - BACKGROUND: In the post-genomic era, the rapid increase in high-throughput data calls for computational tools capable of integrating data of diverse types and facilitating recognition of biologically meaningful patterns within them. For example, protein-protein interaction data sets have been clustered to identify stable complexes, but scientists lack easily accessible tools to facilitate combined analyses of multiple data sets from different types of experiments. Here we present clusterMaker, a Cytoscape plugin that implements several clustering algorithms and provides network, dendrogram, and heat map views of the results. The Cytoscape network is linked to all of the other views, so that a selection in one is immediately reflected in the others. clusterMaker is the first Cytoscape plugin to implement such a wide variety of clustering algorithms and visualizations, including the only implementations of hierarchical clustering, dendrogram plus heat map visualization (tree view), k-means, k-medoid, SCPS, AutoSOME, and native (Java) MCL. RESULTS: Results are presented in the form of three scenarios of use: analysis of protein expression data using a recently published mouse interactome and a mouse microarray data set of nearly one hundred diverse cell/tissue types; the identification of protein complexes in the yeast Saccharomyces cerevisiae; and the cluster analysis of the vicinal oxygen chelate (VOC) enzyme superfamily. For scenario one, we explore functionally enriched mouse interactomes specific to particular cellular phenotypes and apply fuzzy clustering. For scenario two, we explore the prefoldin complex in detail using both physical and genetic interaction clusters. For scenario three, we explore the possible annotation of a protein as a methylmalonyl-CoA epimerase within the VOC superfamily. Cytoscape session files for all three scenarios are provided in the Additional Files section. CONCLUSIONS: The Cytoscape plugin clusterMaker provides a number of clustering algorithms and visualizations that can be used independently or in combination for analysis and visualization of biological data sets, and for confirming or generating hypotheses about biological function. Several of these visualizations and algorithms are only available to Cytoscape users through the clusterMaker plugin. clusterMaker is available via the Cytoscape plugin manager. PMID- 22070253 TI - Special section: the futures of conservation. Introduction. PMID- 22070251 TI - Reevaluating and broadening the definition of genetic rescue. PMID- 22070254 TI - Conservation biology through the lens of a career in salmon conservation. PMID- 22070255 TI - Conservation means behavior. PMID- 22070256 TI - Indigenous alliances for conservation in Bolivia. PMID- 22070257 TI - Finding balance between human need and global stewardship. PMID- 22070258 TI - A vision of conservation from school. PMID- 22070259 TI - Walking the path of environmental Buddhism through compassion and emptiness. PMID- 22070260 TI - Competing cultures of conservation. PMID- 22070261 TI - Cultivating a constituency for conservation. PMID- 22070263 TI - Special section: conservation science in the coming decades. Introduction. PMID- 22070262 TI - Reaching the U.S. public through their patriotism, pastors, and pockets. PMID- 22070264 TI - Systemic conservation, REDD, and the future of the Amazon Basin. PMID- 22070265 TI - Land, food, and biodiversity. PMID- 22070266 TI - Biodiversity offsets and infrastructure. PMID- 22070267 TI - Conservation in sustainable-use tropical forest reserves. PMID- 22070268 TI - Marine protected areas and the governance of marine ecosystems and fisheries. PMID- 22070269 TI - The future of payments for environmental services. PMID- 22070270 TI - Climate change, connectivity, and conservation success. PMID- 22070271 TI - Future human intervention in ecosystems and the critical role for evolutionary biology. PMID- 22070273 TI - Producer-level benefits of sustainability certification. AB - Initiatives certifying that producers of goods and services adhere to defined environmental and social-welfare production standards are increasingly popular. According to proponents, these initiatives create financial incentives for producers to improve their environmental, social, and economic performance. We reviewed the evidence on whether these initiatives have such benefits. We identified peer-reviewed, ex post, producer-level studies in economic sectors in which certification is particularly prevalent (bananas, coffee, fish products, forest products, and tourism operations), classified these studies on the basis of whether their design and methods likely generated credible results, summarized findings from the studies with credible results, and considered how these findings might guide future research. We found 46 relevant studies, most of which focused on coffee and forest products and examined fair-trade and Forest Stewardship Council certification. The methods used in 11 studies likely generated credible results. Of these 11 studies, nine examined the economic effects and two the environmental effects of certification. The results of four of the 11 studies, all of which examined economic effects, showed that certification has producer-level benefits. Hence, the evidence to support the hypothesis that certification benefits the environment or producers is limited. More evidence could be generated by incorporating rigorous, independent evaluation into the design and implementation of projects promoting certification. PMID- 22070272 TI - Scientists' opinions on the global status and management of biological diversity. AB - The large investments needed if loss of biological diversity is to be stemmed will likely lead to increased public and political scrutiny of conservation strategies and the science underlying them. It is therefore crucial to understand the degree of consensus or divergence among scientists on core scientific perceptions and strategies most likely to achieve given objectives. I developed an internet survey designed to elucidate the opinions of conservation scientists. Conservation scientists (n =583) were unanimous (99.5%) in their view that a serious loss of biological diversity is likely, very likely, or virtually certain. Scientists' agreement that serious loss is very likely or virtually certain ranged from 72.8% for Western Europe to 90.9% for Southeast Asia. Tropical coral ecosystems were perceived as the most seriously affected by loss of biological diversity; 88.0% of respondents familiar with that ecosystem type agreed that a serious loss is very likely or virtually certain. With regard to conservation strategies, scientists most often viewed understanding how people and nature interact in certain contexts and the role of biological diversity in maintaining ecosystem function as their priorities. Protection of biological diversity for its cultural and spiritual values and because of its usefulness to humans were low priorities, which suggests that many scientists do not fully support the utilitarian concept of ecosystem services. Many scientists expressed a willingness to consider conservation triage, engage in active conservation interventions, and consider reframing conservation goals and measures of success for conservation of biological diversity in an era of climate change. Although some heterogeneity of opinion is evident, results of the survey show a clear consensus within the scientific community on core issues of the extent and geographic scope of loss of biological diversity and on elements that may contribute to successful conservation strategies in the future. PMID- 22070274 TI - Spatial predictions of phylogenetic diversity in conservation decision making. AB - Considering genetic relatedness among species has long been argued as an important step toward measuring biological diversity more accurately, rather than relying solely on species richness. Some researchers have correlated measures of phylogenetic diversity and species richness across a series of sites and suggest that values of phylogenetic diversity do not differ enough from those of species richness to justify their inclusion in conservation planning. We compared predictions of species richness and 10 measures of phylogenetic diversity by creating distribution models for 168 individual species of a species-rich plant family, the Cape Proteaceae. When we used average amounts of land set aside for conservation to compare areas selected on the basis of species richness with areas selected on the basis of phylogenetic diversity, correlations between species richness and different measures of phylogenetic diversity varied considerably. Correlations between species richness and measures that were based on the length of phylogenetic tree branches and tree shape were weaker than those that were based on tree shape alone. Elevation explained up to 31% of the segregation of species rich versus phylogenetically rich areas. Given these results, the increased availability of molecular data, and the known ecological effect of phylogenetically rich communities, consideration of phylogenetic diversity in conservation decision making may be feasible and informative. PMID- 22070275 TI - Translating effects of inbreeding depression on component vital rates to overall population growth in endangered bighorn sheep. AB - Evidence of inbreeding depression is commonly detected from the fitness traits of animals, yet its effects on population growth rates of endangered species are rarely assessed. We examined whether inbreeding depression was affecting Sierra Nevada bighorn sheep (Ovis canadensis sierrae), a subspecies listed as endangered under the U.S. Endangered Species Act. Our objectives were to characterize genetic variation in this subspecies; test whether inbreeding depression affects bighorn sheep vital rates (adult survival and female fecundity); evaluate whether inbreeding depression may limit subspecies recovery; and examine the potential for genetic management to increase population growth rates. Genetic variation in 4 populations of Sierra Nevada bighorn sheep was among the lowest reported for any wild bighorn sheep population, and our results suggest that inbreeding depression has reduced adult female fecundity. Despite this population sizes and growth rates predicted from matrix-based projection models demonstrated that inbreeding depression would not substantially inhibit the recovery of Sierra Nevada bighorn sheep populations in the next approximately 8 bighorn sheep generations (48 years). Furthermore, simulations of genetic rescue within the subspecies did not suggest that such activities would appreciably increase population sizes or growth rates during the period we modeled (10 bighorn sheep generations, 60 years). Only simulations that augmented the Mono Basin population with genetic variation from other subspecies, which is not currently a management option, predicted significant increases in population size. Although we recommend that recovery activities should minimize future losses of genetic variation, genetic effects within these endangered populations-either negative (inbreeding depression) or positive (within subspecies genetic rescue)-appear unlikely to dramatically compromise or stimulate short-term conservation efforts. The distinction between detecting the effects of inbreeding depression on a component vital rate (e.g., fecundity) and the effects of inbreeding depression on population growth underscores the importance of quantifying inbreeding costs relative to population dynamics to effectively manage endangered populations. PMID- 22070276 TI - The role of natural history institutions and bioinformatics in conservation biology. PMID- 22070278 TI - Genetics of resistance to race TTKSK of Puccinia graminis f. sp. tritici in Triticum monococcum. AB - Race TTKSK (or Ug99) of Puccinia graminis f. sp. tritici possesses virulence to several stem rust resistance genes commonly present in wheat cultivars grown worldwide. New variants detected in the race TTKSK lineage further broadened the virulence spectrum. The identification of sources of genetic resistance to race TTKSK and its relatives is necessary to enable the development and deployment of resistant varieties. Accessions of Triticum monococcum, an A-genome diploid wild and cultivated wheat, have previously been characterized as resistant to stem rust. Three resistance genes were identified and introgressed into hexaploid wheat: Sr21, Sr22, and Sr35. The objective of this study was to determine the genetic control and allelic relationships of resistance to race TTKSK in T. monococcum accessions identified through evaluations at the seedling stage. Generation F(2) progeny of 8 crosses between resistant and susceptible accessions and 13 crosses between resistant accessions of T. monococcum were evaluated with race TTKSK and often with North American races, including races QFCSC, TTTTF, and MCCFC. For a selected population segregating for three genes conferring resistance to race TTKSK, F(2:3) progeny were evaluated with races TTKSK, QFCSC, and TTTTF. In that population, we detected two genes conferring resistance to race TTKSK that are different from Sr21, Sr22, and Sr35. One of the new genes was effective to all races tested. The identification of these genes will facilitate the development of varieties with new resistance to race TTKSK. PMID- 22070279 TI - Biological control of take-all by fluorescent Pseudomonas spp. from Chinese wheat fields. AB - Take-all disease of wheat caused by the soilborne fungus Gaeumannomyces graminis var. tritici is one of the most important root diseases of wheat worldwide. Bacteria were isolated from winter wheat from irrigated and rainfed fields in Hebei and Jiangsu provinces in China, respectively. Samples from rhizosphere soil, roots, stems, and leaves were plated onto King's medium B agar and 553 isolates were selected. On the basis of in vitro tests, 105 isolates (19% of the total) inhibited G. graminis var. tritici and all were identified as Pseudomonas spp. by amplified ribosomal DNA restriction analysis. Based on biocontrol assays, 13 strains were selected for further analysis. All of them aggressively colonized the rhizosphere of wheat and suppressed take-all. Of the 13 strains, 3 (HC9-07, HC13-07, and JC14-07, all stem endophytes) had genes for the biosynthesis of phenazine-1-carboxylic acid (PCA) but none had genes for the production of 2,4 diacetylphloroglucinol, pyoluteorin, or pyrrolnitrin. High-pressure liquid chromatography (HPLC) analysis of 2-day-old cultures confirmed that HC9-07, HC13 07, and JC14-07 produced PCA but no other phenazines were detected. HPLC quantitative time-of-flight 2 mass-spectrometry analysis of extracts from roots of spring wheat colonized by HC9-07, HC13-07, or Pseudomonas fluorescens 2-79 demonstrated that all three strains produced PCA in the rhizosphere. Loss of PCA production by strain HC9-07 resulted in a loss of biocontrol activity. Analysis of DNA sequences within the key phenazine biosynthesis gene phzF and of 16S rDNA indicated that strains HC9-07, HC13-07, and JC14-07 were similar to the well described PCA producer P. fluorescens 2-79. This is the first report of 2-79-like bacteria being isolated from Asia. PMID- 22070280 TI - Modeling cold curing of Pierce's disease in Vitis vinifera 'Pinot Noir' and 'Cabernet Sauvignon' grapevines in California. AB - Pierce's disease (PD) of Vitis vinifera grapevines is caused by the bacterium Xylella fastidiosa, a pathogen with a wide plant host range. Exposure of X. fastidiosa-infected plant tissue to cold temperatures has been shown to be effective at eliminating the pathogen from some plant hosts such as grapevines. This "cold curing" phenomenon suggests itself as a potential method for disease management and perhaps control. We investigated cold therapy of PD-affected 'Pinot Noir' and 'Cabernet Sauvignon' grapevine. In the fall, inoculated plants and controls of each cultivar were transported to each of four field sites in California (Foresthill, McLaughlin, Hopland, and Davis) that differed in the magnitude of cold winter temperatures. A model for progression of the elimination of plant disease in relation to temperature was conceptualized to be a temperature-duration effect, where temperatures below a particular threshold kill X. fastidiosa with increasing efficacy as the temperature decreases to some value <6?C. The temperature effect was modeled as a likelihood of a particular temperature killing the pathogen and is termed the ?killing index?. We developed a mathematical model for cold curing of grapevines inoculated with X. fastidiosa and calibrated the model with cold-curing data collected in a field study. Parameter estimation resulted in lowest sum of squared differences across all 10 trials to be low temperature below which the organism is killed (T(0)) = 6 degrees C, number of hours to achieve 100% cure (N(100)) = 195 h, number of hours to achieve 10% cure (N(10)) = 20 h, and killing index (K(x)) = 0.45 for Pinot Noir and T(0) = 6 degrees C, N(100) = 302 h, N(10) = 170 h, and K(x) = 0.41 for Cabernet Sauvignon. With the parameter estimates optimized by model calibration, the simulation model was effective at predicting cold curing in four locations during the experiment, although there were some differences between Hopland for Pinot Noir and Davis for Cabernet Sauvignon. Using historical temperature data, the model accurately predicted the known severity of PD in other grape-growing regions of California, suggesting that it may have utility in assessing the relative risk of developing PD in proposed new vineyard sites. PMID- 22070282 TI - Anionic heptadecanuclear silver(I) cluster constructed from in situ generated 2 mercaptobenzoic acid and a sulfide anion. AB - A novel anionic heptadecanuclear silver(I) cluster, (NH(4))(17)[(MU(6) S)@Ag(17)(mba)(16)].22H(2)O (1; H(2)mba = 2-mercaptobenzoic acid), was obtained by the reaction of equivalent molar silver oxide and 2,2'-dithiodibenzoic acid (H(2)dtba) under ultrasonic conditions at 50 degrees C. Complex 1 is a discrete cluster comprised of unexpected mba ligands on the shell and a MU(6)-S(2-) ion in the core, suggesting the occurrence of in situ S-S and S-C(sp(2)) bond cleavages of the H(2)dtba ligand. This novel cluster displays moderate orange-red emission in the solid state at room temperature. PMID- 22070284 TI - Deoxynivalenol, deoxynivalenol-3-glucoside, and enniatins: the major mycotoxins found in cereal-based products on the Czech market. AB - Fusarium toxins, Alternaria toxins, and ergot alkaloids represent common groups of mycotoxins that can be found in cereals grown under temperate climatic conditions. Because most of them are chemically and thermally stable, these toxic fungal secondary metabolites might be transferred from grains into the final products. To get information on the commensurate contamination of various cereal based products collected from the Czech retail market in 2010, the occurrence of "traditional" mycotoxins such as groups of A and B trichothecenes and zearalenone, less routinely determined Alternaria toxins (alternariol, alternariol monomethyl ether and altenuene), ergot alkaloids (ergosine, ergocryptine, ergocristine, and ergocornine) and "emerging" mycotoxins (enniatins A, A1, B, and B1 and beauvericin) were monitored. In a total 116 samples derived from white flour and mixed flour, breakfast cereals, snacks, and flour, only trichothecenes A and B and enniatins were found. Deoxynivalenol was detected in 75% of samples with concentrations ranging from 13 to 594 MUg/kg, but its masked form, deoxynivalenol-3-beta-d-glucoside, has an even higher incidence of 80% of samples, and concentrations ranging between 5 and 72 MUg/kg were detected. Nivalenol was found only in three samples at levels of 30 MUg/kg. For enniatins, all of the samples investigated were contaminated with at least one of four target enniatins. Enniatin A was detected in 97% of samples (concentration range of 20-2532 MUg/kg) followed by enniatin B with an incidence in 91% of the samples (concentration range of 13-941 MUg/kg) and enniatin B1 with an incidence of 80% in the samples tested (concentration range of 8-785 MUg/kg). Enniatin A1 was found only in 44% of samples at levels ranging between 8 and 851 MUg/kg. PMID- 22070283 TI - Seizures and epilepsy in Alzheimer's disease. AB - Many studies have shown that patients with Alzheimer's disease (AD) are at increased risk for developing seizures and epilepsy. However, reported prevalence and incidence of seizures and relationship of seizures to disease measures such as severity, outcome, and progression vary widely between studies. We performed a literature review of the available clinical and epidemiological data on the topic of seizures in patients with AD. We review seizure rates and types, risk factors for seizures, electroencephalogram (EEG) studies, and treatment responses. Finally, we consider limitations and methodological issues. There is considerable variability in the reported prevalence and incidence of seizures in patients with AD-with reported lifetime prevalence rates of 1.5-64%. More recent, prospective, and larger studies in general report lower rates. Some, but not all, studies have noted increased seizure risk with increasing dementia severity or with younger age of AD onset. Generalized convulsive seizures are the most commonly reported type, but often historical information is the only basis used to determine seizure type and the manifestation of seizures may be difficult to distinguish from other behaviors common in demented patients. EEG has infrequently been performed and reported. Data on treatment of seizures in AD are extremely limited. Similarly, the relationship between seizures and cognitive impairment in AD is unclear. We conclude that the literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps. PMID- 22070285 TI - Catalytic asymmetric synthesis of stable oxetenes via Lewis acid-promoted [2+2] cycloaddition. AB - A highly enantioselective and atom-economical [2 + 2] cycloaddition of various alkynes with trifluoropyruvate using a dicationic (S)-BINAP-Pd catalyst has been established. This is the first enantioselective synthesis of stable oxetene derivatives, whose structure has been clarified by X-ray analysis. This catalytic process offers a practical synthetic method for oxetene derivatives (catalyst loading: up to 0.1 mol %), which can serve as novel chiral building blocks for pharmaceuticals and agrochemicals and can also be transformed into a variety of enantiomerically enriched CF(3)-substituted compounds with high stereoselectivity. PMID- 22070286 TI - Identification of key residues for protein conformational transition using elastic network model. AB - Proteins usually undergo conformational transitions between structurally disparate states to fulfill their functions. The large-scale allosteric conformational transitions are believed to involve some key residues that mediate the conformational movements between different regions of the protein. In the present work, a thermodynamic method based on the elastic network model is proposed to predict the key residues involved in protein conformational transitions. In our method, the key functional sites are identified as the residues whose perturbations largely influence the free energy difference between the protein states before and after transition. Two proteins, nucleotide binding domain of the heat shock protein 70 and human/rat DNA polymerase beta, are used as case studies to identify the critical residues responsible for their open closed conformational transitions. The results show that the functionally important residues mainly locate at the following regions for these two proteins: (1) the bridging point at the interface between the subdomains that control the opening and closure of the binding cleft; (2) the hinge region between different subdomains, which mediates the cooperative motions between the corresponding subdomains; and (3) the substrate binding sites. The similarity in the positions of the key residues for these two proteins may indicate a common mechanism in their conformational transitions. PMID- 22070287 TI - Enhanced diffusion in conic channels by means of geometric stochastic resonance. AB - Geometric stochastic resonance of Brownian particles diffusing across a converging conic channel subject to oscillating forces is studied in this paper. Conic channel geometries have been previously considered as a model for transport of particles in biological membranes, zeolites, and nanostructures. For this system, a broad excess peak of the effective diffusion above the free diffusion limit is exhibited over a wide range of frequencies, suggesting a synchronization effect in the confining geometry as particles respond to the periodic modulation of the external force. This indicates that the geometric stochastic resonance effect with unbiased ac forces can be exploited for improving the transport of particles in complex geometries. PMID- 22070288 TI - An off-lattice, self-learning kinetic Monte Carlo method using local environments. AB - We present a method called local environment kinetic Monte Carlo (LE-KMC) method for efficiently performing off-lattice, self-learning kinetic Monte Carlo (KMC) simulations of activated processes in material systems. Like other off-lattice KMC schemes, new atomic processes can be found on-the-fly in LE-KMC. However, a unique feature of LE-KMC is that as long as the assumption that all processes and rates depend only on the local environment is satisfied, LE-KMC provides a general algorithm for (i) unambiguously describing a process in terms of its local atomic environments, (ii) storing new processes and environments in a catalog for later use with standard KMC, and (iii) updating the system based on the local information once a process has been selected for a KMC move. Search, classification, storage and retrieval steps needed while employing local environments and processes in the LE-KMC method are discussed. The advantages and computational cost of LE-KMC are discussed. We assess the performance of the LE KMC algorithm by considering test systems involving diffusion in a submonolayer Ag and Ag-Cu alloy films on Ag(001) surface. PMID- 22070289 TI - Anomalous kinetics in diffusion limited reactions linked to non-Gaussian concentration probability distribution function. AB - We investigate anomalous reaction kinetics related to segregation in the one dimensional reaction-diffusion system A + B -> C. It is well known that spatial fluctuations in the species concentrations cause a breakdown of the mean-field behavior at low concentration values. The scaling of the average concentration with time changes from the mean-field t(-1) to the anomalous t(-1/4) behavior. Using a stochastic modeling approach, the reaction-diffusion system can be fully characterized by the multi-point probability distribution function (PDF) of the species concentrations. Its evolution is governed by a Fokker-Planck equation with moving boundaries, which are determined by the positivity of the species concentrations. The concentration PDF is in general non-Gaussian. As long as the concentration fluctuations are small compared to the mean, the PDF can be approximated by a Gaussian distribution. This behavior breaks down in the fluctuation dominated regime, for which anomalous reaction kinetics are observed. We show that the transition from mean field to anomalous reaction kinetics is intimately linked to the evolution of the concentration PDF from a Gaussian to non-Gaussian shape. This establishes a direct relationship between anomalous reaction kinetics, incomplete mixing and the non-Gaussian nature of the concentration PDF. PMID- 22070291 TI - Optimization of a genetic algorithm for searching molecular conformer space. AB - We present two sets of tunings that are broadly applicable to conformer searches of isolated molecules using a genetic algorithm (GA). In order to find the most efficient tunings for the GA, a second GA--a meta-genetic algorithm--was used to tune the first genetic algorithm to reliably find the already known a priori correct answer with minimum computational resources. It is shown that these tunings are appropriate for a variety of molecules with different characteristics, and most importantly that the tunings are independent of the underlying model chemistry but that the tunings for rigid and relaxed surfaces differ slightly. It is shown that for the problem of molecular conformational search, the most efficient GA actually reduces to an evolutionary algorithm. PMID- 22070290 TI - Rapid calculation of partition functions and free energies of fluids. AB - The partition function (Q) is a central quantity in statistical mechanics. All the thermodynamic properties can be derived from it. Here we show how the partition function of fluids can be calculated directly from simulations; this allows us to obtain the Helmholtz free energy (F) via F = -k(B)T ln Q. In our approach, we divide the density of states, assigning half of the configurations found in a simulation to a high-energy partition and half to a low-energy partition. By recursively dividing the low-energy partition into halves, we map out the complete density of states for a continuous system. The result allows free energy to be calculated directly as a function of temperature. We illustrate our method in the context of the free energy of water. PMID- 22070292 TI - Large-scale symmetry-adapted perturbation theory computations via density fitting and Laplace transformation techniques: investigating the fundamental forces of DNA-intercalator interactions. AB - Symmetry-adapted perturbation theory (SAPT) provides a means of probing the fundamental nature of intermolecular interactions. Low-orders of SAPT (here, SAPT0) are especially attractive since they provide qualitative (sometimes quantitative) results while remaining tractable for large systems. The application of density fitting and Laplace transformation techniques to SAPT0 can significantly reduce the expense associated with these computations and make even larger systems accessible. We present new factorizations of the SAPT0 equations with density-fitted two-electron integrals and the first application of Laplace transformations of energy denominators to SAPT. The improved scalability of the DF-SAPT0 implementation allows it to be applied to systems with more than 200 atoms and 2800 basis functions. The Laplace-transformed energy denominators are compared to analogous partial Cholesky decompositions of the energy denominator tensor. Application of our new DF-SAPT0 program to the intercalation of DNA by proflavine has allowed us to determine the nature of the proflavine-DNA interaction. Overall, the proflavine-DNA interaction contains important contributions from both electrostatics and dispersion. The energetics of the intercalator interaction are are dominated by the stacking interactions (two thirds of the total), but contain important contributions from the intercalator backbone interactions. It is hypothesized that the geometry of the complex will be determined by the interactions of the intercalator with the backbone, because by shifting toward one side of the backbone, the intercalator can form two long hydrogen-bonding type interactions. The long-range interactions between the intercalator and the next-nearest base pairs appear to be negligible, justifying the use of truncated DNA models in computational studies of intercalation interaction energies. PMID- 22070293 TI - A combination of the tree-code and IPS method to simulate large scale systems by molecular dynamics. AB - An IPS/Tree method which is a combination of the isotropic periodic sum (IPS) method and tree-based method was developed for large-scale molecular dynamics simulations, such as biological and polymer systems, that need hundreds of thousands of molecules. The tree-based method uses a hierarchical tree structure to reduce the calculation cost of long-range interactions. IPS/Tree is an efficient method like IPS/DFFT, which is a combination of the IPS method and FFT in calculating large-scale systems that require massively parallel computers. The IPS method has two different versions: IPSn and IPSp. The basic idea is the same expect for the fact that the IPSn method is applied to calculations for point charges, while the IPSp method is used to calculate polar molecules. The concept of the IPS/Tree method is available for both IPSn and IPSp as IPSn/Tree and IPSp/Tree. Even though the accuracy of the Coulomb forces with tree-based method is well known, the accuracy for the combination of the IPS and tree-based methods is unclear. Therefore, in order to evaluate the accuracy of the IPS/Tree method, we performed molecular dynamics simulations for 32,000 bulk water molecules, which contains around 10(5) point charges. IPSn/Tree and IPSp/Tree were both applied to study the interaction calculations of Coulombic forces. The accuracy of the Coulombic forces and other physical properties of bulk water systems were evaluated. The IPSp/Tree method not only has reasonably small error in estimating Coulombic forces but the error was almost the same as the theoretical error of the ordinary tree-based method. These facts show that the algorithm of the tree based method can be successfully applied to the IPSp method. On the other hand, the IPSn/Tree has a relatively large error, which seems to have been derived from the interaction treatment of the original IPSn method. The self-diffusion and radial distribution functions of water were calculated each by both the IPSn/Tree and IPSp/Tree methods, where both methods showed reasonable agreement with the Ewald method. In conclusion, the IPSp/Tree method is a potentially fast and sufficiently accurate technique for predicting transport coefficients and liquid structures of water in a homogeneous system. PMID- 22070294 TI - Construction of a disorder variable from Steinhardt order parameters in binary mixtures at high densities in three dimensions. AB - Using molecular dynamics simulation, we investigate the structural disorder in crystal, polycrystal, and glass in a Lennard-Jones binary mixture composed of N(1) + N(2) = 4096 particles at a low temperature in three dimensions. The size ratio sigma(2)/sigma(1) between the large and small particles is either 1.2 or 1.4. The crossovers among these states occur, as the composition of the large particles c = N(2)/(N(1) + N(2)) is varied. We define a disorder variable D(j) for each particle j in terms of local bond order parameters based on spherical harmonics (Steinhardt order parameters). Stacking faults and grain boundaries in fcc polycrystal and mesoscopic structural heterogeneity in glass are then visualized. At small c, disturbances of large particles is stronger for larger sigma(2)/sigma(1). At large c, the transition between glass and polycrystal occurs nearly discontinuously at c = c(c) ~ 0.8. At sigma(2)/sigma(1) = 1.4, microphase separation occurs in polycrystal states with c > c(c), where fcc crystal grains comprising the large particles are enclosed by amorphous layers composed of the two particle species. PMID- 22070295 TI - Efficient computation of adiabatic populations in multi-mode Jahn-Teller systems through the use of effective vibrational modes. AB - A highly efficient scheme for computing adiabatic electronic populations in multi mode Jahn-Teller systems is presented. It relies on the transformation to an effective-mode vibrational basis in which the relevant quantities depend on the coordinates of a single mode only. In this way, the generally tedious numerical evaluation of high-dimensional integrals is avoided and replaced by one dimensional integrations. The effective-mode scheme is applied to a variety of two-mode and three-mode Jahn-Teller systems and gives a typical speedup of about two to three orders of magnitude as compared to the direct evaluation of the adiabatic populations. The gain grows rapidly with the numbers of modes. PMID- 22070296 TI - Stability analysis of multiple nonequilibrium fixed points in self-consistent electron transport calculations. AB - We present a method to perform stability analysis of nonequilibrium fixed points appearing in self-consistent electron transport calculations. The nonequilibrium fixed points are given by the self-consistent solution of stationary, nonlinear kinetic equation for single-particle density matrix. We obtain the stability matrix by linearizing the kinetic equation around the fixed points and analyze the real part of its spectrum to assess the asymptotic time behavior of the fixed points. We derive expressions for the stability matrices within Hartree-Fock and linear response adiabatic time-dependent density functional theory. The stability analysis of multiple fixed points is performed within the nonequilibrium Hartree Fock approximation for the electron transport through a molecule with a spin degenerate single level with local Coulomb interaction. PMID- 22070297 TI - Elastic scattering and rotational excitation of nitrogen molecules by sodium atoms. AB - A quantal study of the rotational excitation of nitrogen molecules by sodium atoms is carried out. We present the two-dimensional potential energy surface of the NaN(2) complex, with the N(2) molecule treated as a rigid rotor. The interaction potential is computed using the spin unrestricted coupled-cluster method with single, double, and perturbative triple excitations (UCCSD(T)). The long-range part of the potential is constructed from the dynamic electric dipole polarizabilities of Na and N(2). The total, differential, and momentum transfer cross sections for rotationally elastic and inelastic transitions are calculated using the close-coupling approach for energies between 5 cm(-1) and 1500 cm(-1). The collisional and momentum transfer rate coefficients are calculated for temperatures between 100 K and 300 K, corresponding to the conditions under which Na-N(2) collisions occur in the mesosphere. PMID- 22070298 TI - The X2Sigma+ state of LiCa studied by Fourier-transform spectroscopy. AB - The paper reports on a successful observation of high resolution Fourier transform spectra of LiCa. The fine structure of the ground state was observed and attributed to effective spin-rotation interaction. The experimental observations are described by two models using potential energy curves. One of them takes into account the fine structure splitting by means of effective constants, the other by means of a R dependent function gamma(R), built in the radial Schrodinger equation. Ab initio calculations were performed for gamma(R) which comes close to the experimental function. PMID- 22070299 TI - The Jahn-Teller effect in the triply degenerate electronic state of methane radical cation. AB - A quantum dynamics study is performed to examine the complex nuclear motion underlying the first photoelectron band of methane. The broad and highly overlapping structures of the latter are found to originate from transitions to the ground electronic state, X(2)T(2), of the methane radical cation. Ab initio calculations have also been carried out to establish the potential energy surfaces for the triply degenerate electronic manifold of CH(4)(+). A suitable diabatic vibronic Hamiltonian has been devised and the nonadiabatic effects due to Jahn-Teller conical intersections on the vibronic dynamics investigated in detail. The theoretical results show fair accord with experiment. PMID- 22070300 TI - Hydrophobic interactions in presence of osmolytes urea and trimethylamine-N oxide. AB - Molecular dynamics simulations were carried out to study the influences of two naturally occurring osmolytes, urea, and trimethylamine-N-oxide (TMAO) on the hydrophobic interactions between neopentane molecules. In this study, we used two different models of neopentane: One is of single united site (UA) and another contains five-sites. We observe that, these two neopentane models behave differently in pure water as well as solutions containing osmolytes. Presence of urea molecules increases the stability of solvent-separated state for five-site model, whereas osmolytes have negligible effect in regard to clustering of UA model of neopentane. For both models, dehydration of neopentane and preferential solvation of it by urea and TMAO over water molecules are also observed. We also find the collapse of the second-shell of water by urea and water structure enhancement by TMAO. The orientational distributions of water molecules around different layers of neopentane were also calculated and we find that orientation of water molecules near to hydrophobic moiety is anisotropic and osmolytes have negligible effect on it. We also observe osmolyte-induced water-water hydrogen bond life time increase in the hydration shell of neopentane as well as in the subsequent water layers. PMID- 22070301 TI - Singlet state relaxation via scalar coupling of the second kind. AB - The contribution of scalar coupling relaxation of the second kind on the relaxation behaviour of nuclear spin singlet states has been derived. The analytical equation found for the relaxation rate constant of singlet state has been compared to the equation for the relaxation of longitudinal magnetization in order to find the conditions for which the singlet state remains long-lived even in the presence of this scalar relaxation mechanism. These results are relevant when the singlet state is formed in molecules with more than two interacting spins. PMID- 22070302 TI - Spectroscopic properties of alkali atoms embedded in Ar matrix. AB - We present a theoretical investigation of visible absorption and related luminescence of alkali atoms (Li, Na, and K) embedded in Ar matrix. We used a model based on core polarization pseudopotentials, which allows us to determine accurately the gas-to-matrix shifts of various trapping sites. The remarkable agreement between our calculated results and the experimental spectra recorded by several authors allows us to establish a clear assignment of the observed spectra, which are made of contributions from crystalline sites on the one hand, and of grain boundary sites on the other hand. Our study reveals remarkably large Stokes shifts, up to 9000 cm(-1), which could be observed experimentally to identify definitely the trapping sites. PMID- 22070304 TI - Photoisomerization dynamics of 3,3'-diethyloxadicarbocyanine iodide in ionic liquids: breakdown of hydrodynamic Kramers model. AB - Photoisomerization dynamics of 3,3'-diethyloxadicarbocyanine iodide (DODCI) has been examined in a series of 1-alkyl-3-methylimidazolium (alkyl = methyl, ethyl, propyl, butyl, and hexyl) bis(trifluoromethylsulfonyl)imides by measuring its fluorescence lifetimes and quantum yields. This study has essentially been undertaken to find out whether the process of photoisomerization of DODCI in ionic liquids is different compared to that observed in conventional solvents such as alcohols. Activation energy of the reaction has been attained with the aid of isoviscosity plots and was found to be 22 +/- 3 kJ mol(-1), which is a factor of two higher compared to that obtained in alcohols. The significantly higher activation energy obtained in bis(trifluoromethylsulfonyl)imides compared to alcohols is probably due to the highly ordered nature of the ionic liquids, which hinders the twisting process. Kramers theory has been applied to understand the reduced isomerization rate constants in terms of solvent friction. As in case of alcohols, the isomerization data could not be explained by the Kramers model. However, a power law relation, which is a phenomenological functional form, could mimic the observed trend. PMID- 22070303 TI - Electron interaction with nitromethane embedded in helium droplets: attachment and ionization measurements. AB - Results of a detailed study on electron interactions with nitromethane (CH(3)NO(2)) embedded in helium nanodroplets are reported. Anionic and cationic products formed are analysed by mass spectrometry. When the doped helium droplets are irradiated with low-energy electrons of about 2 eV kinetic energy, exclusively parent cluster anions (CH(3)NO(2))(n)(-) are formed. At 8.5 eV, three anion cluster series are observed, i.e., (CH(3)NO(2))(n)(-), [(CH(3)NO(2))(n)-H]( ), and (CH(3)NO(2))(n)NO(2)(-), the latter being the most abundant. The results obtained for anions are compared with previous electron attachment studies with bare nitromethane and nitromethane condensed on a surface. The cation chemistry (induced by electron ionization of the helium matrix at 70 eV and subsequent charge transfer from He(+) to the dopant cluster) is dominated by production of methylated and protonated nitromethane clusters, (CH(3)NO(2))(n)CH(3)(+) and (CH(3)NO(2))(n)H(+). PMID- 22070305 TI - Debye to non-Debye scaling of the Boson peak dynamics: critical behavior and local disorder in vitreous germania. AB - We report on the observation of a significant softening of the Boson peak (BP) frequency of vitreous GeO(2) above the glass transition temperature. The softening reminds a critical trend, with a transition temperature intermediate between the glass transition temperature, T(g), and the melting point. The softening of the BP frequency corresponds to a transition from a region dominated by Debye scaling to a non-Debye one. Below T(g) the density of vibrational states varies according to the modification of the elastic continuum medium. Above T(g) the relevant softening of the BP modes can be explained by a broadening of the distribution of elastic constants between neighboring atoms, induced by the structural rearrangement. These findings are discussed together with recent experimental and theoretical results on the low frequency vibrations in glasses. PMID- 22070306 TI - "Stubborn" triaminotrinitrobenzene: unusually high chemical stability of a molecular solid to 150 GPa. AB - We report an unexpectedly high chemical stability of molecular solid 1,3,5 triamino-2,4,6-trinitrobenzene (TATB) under static high pressures. In contrast to the high-pressure behavior of the majority of molecular solids, TATB remains both chemically stable and an insulator to 150 GPa--well above the predicted metallization pressure of 120 GPa. Single crystal studies have shown that TATB exhibits pressure-induced Raman changes associated with two subtle structural phase transitions at 28 and 56 GPa. These phase transitions are accompanied by remarkable color changes, from yellow to orange and to dark red with increasing pressure. We suggest that the high-stability of TATB arises as a result of its hydrogen-bonded aromatic two-dimensional (2D) layered structure and highly repulsive interlayer interaction, hindering the formation of 3D networks or metallic states. PMID- 22070307 TI - H2O and D2 mixtures under pressure: spectroscopy and proton exchange kinetics. AB - We have investigated the pressure-induced spectral changes and the proton exchange reactions of D(2)-H(2)O mixtures to 64 GPa using micro-Raman spectroscopy. The results show the profound difference in the rotational and vibrational Raman spectra of hydrogen isotopes from those of the pure samples, showing the vibrational modes at higher frequencies and continuing to increase with pressure without apparent turnover. This indicates the repulsive nature of D(2)-H(2)O interaction without hydrogen bonds between the two and, thus, interstitial fillings of D(2) molecules into the bcc-like ice lattice. The spectral analysis using the Morse potential yields a hydrogen bond distance of 0.734 A at 6 GPa--slightly shorter than that in pure--attributed to the repulsive interaction. The pressure-dependent spectral changes suggest that the proton ordering transition in the ice lattice occurs over a large pressure range between 28 and 50 GPa, which is substantially lower than that of pure ice (40-80 GPa). This again indicates the presence of high internal pressure arising from the repulsive interaction. The Raman spectra show evidences that the proton exchange occurs in various phases including in solid D(2) and H(2)O mixtures. Based on the time-dependent spectral changes, we obtained the proton exchange rates of k ~ 0.085 h(-1) at 0.2 GPa in fluid D(2) and water mixtures, k ~ 0.03 h(-1) and 0.003 h(-1) at 2 GPa and 4 GPa, respectively, in fluid D(2)-ice mixtures, and k ~ 10( 3) h(-1) at 8 GPa in solid D(2) and ice mixtures. PMID- 22070308 TI - Interpreting single turnover catalysis measurements with constrained mean dwell times. AB - Observation of a chemical transformation at the single-molecule level yields a detailed view of kinetic pathways contributing to the averaged results obtained in a bulk measurement. Studies of a fluorogenic reaction catalyzed by gold nanoparticles have revealed heterogeneous reaction dynamics for these catalysts. Measurements on single nanoparticles yield binary trajectories with stochastic transitions between a dark state in which no product molecules are adsorbed and a fluorescent state in which one product molecule is present. The mean dwell time in either state gives information corresponding to a bulk measurement. Quantifying fluctuations from mean kinetics requires identifying properties of the fluorescence trajectory that are selective in emphasizing certain dynamic processes according to their time scales. We propose the use of constrained mean dwell times, defined as the mean dwell time in a state with the constraint that the immediately preceding dwell time in the other state is, for example, less than a variable time. Calculations of constrained mean dwell times for a kinetic model with dynamic disorder demonstrate that these quantities reveal correlations among dynamic fluctuations at different active sites on a multisite catalyst. Constrained mean dwell times are determined from measurements of single nanoparticle catalysis. The results indicate that dynamical fluctuations at different active sites are correlated, and that especially rapid reaction events produce particularly slowly desorbing product molecules. PMID- 22070309 TI - Surface and confinement effects on the dielectric relaxation of a monohydroxy alcohol. AB - 2-ethyl-1-hexanol (2E1H) was confined to the surface of a collagen matrix at various concentration levels c. Dielectric spectroscopy revealed that upon decreasing c, the alcohol's prominent hydrogen-bond mediated Debye-like relaxation broadens and turns nonexponential. This destabilization of the supramolecular association is accompanied by an increasing relative strength of the structural relaxation in 2E1H up to a point beyond which the two processes are merged when the solvent molecules are sufficiently diluted. These results demonstrate that the contribution of the Debye-like relaxation can be completely suppressed and concomitantly the limit of a simple, nonassociating liquid is reached. Confinement of the alcohol in a monolithic glass with nanoscopic pores subjected to different internal surface treatments is also demonstrated to bear a large impact on the relative strengths of the two processes. PMID- 22070310 TI - Nuclear magnetic resonance and dielectric noise study of spectral densities and correlation functions in the glass forming monoalcohol 2-ethyl-1-hexanol. AB - The spectral densities related to various relaxation processes of the glass former 2-ethyl-1-hexanol (2E1H), a monohydroxy alcohol, are probed using several nuclear magnetic resonance (NMR) experiments as well as via dielectric noise spectroscopy (DNS). On the basis of the spectral density relating to voltage fluctuations, i.e., without the application of external electrical fields, DNS enables the detection of the structural relaxation and of the prominent, about two decades slower Debye process. The NMR-detected spectral density, sensitive to the orientational fluctuations of the hydroxyl deuteron, also reveals dynamics slower than the structural relaxation, but not as slow as the Debye process. Rotational and translational correlation functions of 2E1H are probed using stimulated-echo NMR techniques which could only resolve the structural dynamics or faster processes. The experimental results are discussed with reference to models that were suggested to describe the dynamics in supercooled alcohols. PMID- 22070311 TI - Charge transfer dynamics of 3,4,9,10-perylene-tetracarboxylic-dianhydride molecules on Au(111) probed by resonant photoemission spectroscopy. AB - Charge transfer dynamics across the lying-down 3,4,9,10-perylene-tetracarboxylic dianhydride (PTCDA) organic semiconductor molecules on Au(111) interface has been investigated using the core-hole clock implementation of resonant photoemission spectroscopy. It is found that the charge transfer time scale at the PTCDA/Au(111) interface is much larger than the C 1s core-hole lifetime of 6 fs, indicating weak electronic coupling between PTCDA and the gold substrate due to the absence of chemical reaction and/or bonding. PMID- 22070312 TI - Structure, stability, and mobility of small Pd clusters on the stoichiometric and defective TiO2 (110) surfaces. AB - We report on the structure and adsorption properties of Pd(n) (n = 1-4) clusters supported on the rutile TiO(2) (110) surfaces with the possible presence of a surface oxygen vacancy or a subsurface Ti-interstitial atom. As predicted by the density functional theory, small Pd clusters prefer to bind to the stoichiometric titania surface or at sites near subsurface Ti-interstitial atoms. The adsorption of Pd clusters changes the electronic structure of the underlying surface. For the surface with an oxygen vacancy, the charge localization and ferromagnetic spin states are found to be largely attenuated owing to the adsorption of Pd clusters. The potential energy surfaces of the Pd monomer on different types of surfaces are also reported. The process of sintering is then simulated via the Metropolis Monte Carlo method. The presence of oxygen vacancy likely leads to the dissociation of Pd clusters. On the stoichiometric surface or surface with Ti interstitial atom, the Pd monomers tend to sinter into larger clusters, whereas the Pd dimer, trimer, and tetramer appear to be relatively stable below 600 K. This result agrees with the standard sintering model of transition metal clusters and experimental observations. PMID- 22070313 TI - Wet nanogranular materials: colloidal glass and gel. AB - Partially wet granular medium is a mouldable material due to capillary cohesion and its behavior plays key roles in geophysics. However, completely wet nanogranules may also demonstrate mouldable properties via van der Waals attraction and they exhibit colloidal glass or gel characteristics, depending on the solvent. As solvent-enhanced attractions prevail, phase separation is observed and nanogranular gel can be obtained. In contrast, as cage effects dominate, the stable slurry is seen and the nanogranular glass can be prepared. Upon surfactant addition, however, the arrested glass state changes into colloidal gel due to the formation of hydrogen bonds between nanogranules. PMID- 22070314 TI - Quasistatic computer simulations of shear behavior of water nanoconfined between mica surfaces. AB - We combine the grand canonical Monte Carlo and molecular dynamics techniques to simulate the shear response of water under a 9.2 A confinement between two parallel sheets of muscovite mica. The shear deformation is modeled in the quasistatic regime corresponding to an infinitely small shear rate. It is found that the confined water film is capable of sustaining shear stress, as is characteristic of solids, while remaining fluid-like in respect of molecular mobility and lateral order. An important information is obtained by splitting the stress tensor components into contributions arising from the interaction of the opposing mica sheets between themselves and their interaction with water. The mica-mica contributions to shear stress show a strong anisotropy dictated by the alignment of the surface K(+) ions in chains along the x axis. On shearing in this direction, the mica-mica contribution to shear stress is negligible, so that the shear resistance is determined by the water interlayer. By contrast, in the y direction, the mica-mica contribution to shear resistance is dominant. The water mica contribution is slightly less in magnitude but opposite in sign. As a consequence, the mica-mica contribution is largely canceled out. The physics behind this cancellation is the screening of the electrostatic interactions of the opposing surface K(+) ions by water molecules. PMID- 22070315 TI - A theory of single-electron non-adiabatic tunneling through a small metal nanoparticle with due account of the strong interaction of valence electrons with phonons of the condensed matter environment. AB - A theory of electrochemical behavior of small metal nanoparticles (NPs) which is governed both by the charging effect and the effect of the solvent reorganization on the dynamic of the electron transfer (ET) is considered under ambient conditions. The exact expression for the rate constant of ET from an electrode to NP which is valid for all values of the reorganization free energy E(r), bias voltage, and overpotential is obtained in the non-adiabatic limit. The tunnel current/overpotential relations are studied and calculated for different values of the bias voltage and E(r). The effect of E(r) on the full width at half maximum of the charging peaks is investigated at different values of the bias voltage. The differential conductance/bias voltage and the tunnel current/bias voltage dependencies are also studied and calculated. It is shown that, at room temperature, the pronounced Coulomb blockade oscillations in the differential conductance/bias voltage curves and the noticeable Coulomb staircase in the tunnel current/bias voltage relations are observed only at rather small values of E(r) in the case of the strongly asymmetric tunneling contacts. PMID- 22070316 TI - Atomistic surface erosion and thin film growth modelled over realistic time scales. AB - We present results of atomistic modelling of surface growth and sputtering using a multi-time scale molecular dynamics-on-the-fly kinetic Monte Carlo scheme which allows simulations to be carried out over realistic experimental times. The method uses molecular dynamics to model the fast processes and then calculates the diffusion barriers for the slow processes on-the-fly, without any preconceptions about what transitions might occur. The method is applied to the growth of metal and oxide materials at impact energies typical for both vapour deposition and magnetron sputtering. The method can be used to explain growth processes, such as the filling of vacancies and the formation of stacking faults. By tuning the variable experimental parameters on the computer, a parameter set for optimum crystalline growth can be determined. The method can also be used to model sputtering where the particle interactions with the surface occur at a higher energy. It is shown how a steady state can arise in which interstitial clusters are continuously being formed below the surface during an atom impact event which also recombine or diffuse to the surface between impact events. For fcc metals the near surface region remains basically crystalline during the erosion process with a pitted topography which soon attains a steady state roughness. PMID- 22070317 TI - Coverage effects in the adsorption of H2 on Pd(100) studied by ab initio molecular dynamics simulations. AB - The interaction of hydrogen with palladium surfaces represents one of the model systems for the study of the adsorption and absorption at metal surfaces. Theoretical gas-surface dynamics studies have usually concentrated on the adsorption dynamics on clean surfaces. Only recently it has become possible, based on advances in the electronic structure codes and improvements in the computer power, to address the much more complex problem of the adsorption dynamics on precovered surfaces. Here, I present ab initio molecular dynamics (AIMD) simulations based on periodic density functional theory (DFT) calculations of the adsorption of H(2) on hydrogen-precovered Pd(100) for a broad variety of different hydrogen coverage structures. The stability of the adsorbate structures and the adsorption dynamics are analyzed in detail. Calculated sticking probabilities are larger than expected for pure site-blocking consistent with experimental results. It turns out that the adsorption dynamics on the strongly corrugated surfaces depends sensitively on the dynamic response of the substrate atoms upon the impact of the impinging H(2) molecules. In addition, for some structures the adsorption probability was evaluated as a function of the kinetic energy. Adsorbate structures corresponding to the same coverage but with different arrangements of the adsorbed atoms can lead to a qualitatively different dependence of the adsorption probability on the kinetic energy changing also the order of the preferred structures, as far as the adsorption is concerned, as a function of the kinetic energy. This indicates that dynamical effects such as steering and dynamical trapping play an important role in the adsorption on these precovered substrates. PMID- 22070318 TI - Structural properties of atactic polystyrene adsorbed onto solid surfaces. AB - In the present work, we are studying the local conformation of chains in a thin film of polystyrene adsorbed on a solid substrate by using atomistically detailed simulations. The simulations are carried out by using the readily available and massively parallel molecular dynamics code known as LAMMPS. In particular, a special emphasis is given to the density and orientation of side chains (which consist of phenyl groups and methylene units) at solid/polymer and polymer/vacuum interfaces. Three types of substrates were used in our study: alpha-quartz, graphite, and amorphous silica. Our investigation was restricted to atactic polystyrene. Our results show that the density and structural properties of side chains depend on the type of surface. An excess of phenyl rings is observed near the alpha-quartz substrate while the film adsorbed on graphite is depleted in C(6)H(5). Moreover, the orientation of the rings and methylene units on the substrate/film interface show a strong dependence on the type of the substrate, while the rings at the film/vacuum interface show a marked tendency to point outward, away from the film. The results we obtained are in a large part in good agreement with previous experimental and simulation results. PMID- 22070319 TI - Structure and dynamics of water confined in silica nanopores. AB - We report the results of molecular simulation of water in silica nanopores at full hydration and room temperature. The model systems are approximately cylindrical pores in amorphous silica, with diameters ranging from 20 to 40 A. The filled pores are prepared using grand canonical Monte Carlo simulation and molecular dynamics simulation is used to calculate the water structure and dynamics. We found that water forms two distinct molecular layers at the interface and exhibits uniform, but somewhat lower than bulk liquid, density in the core region. The hydrogen bond density profile follows similar trends, with lower than bulk density in the core and enhancements at the interface, due to hydrogen bonds between water and surface non-bridging oxygens and OH groups. Our studies of water dynamics included translational mean squared displacements, orientational time correlations, survival probabilities in interfacial shells, and hydrogen bond population relaxation. We found that the radial-axial anisotropy in translational motion largely follows the predictions of a model of free diffusion in a cylinder. However, both translational and rotational water mobilities are strongly dependent on the proximity to the interface, with pronounced slowdown in layers near the interface. Within these layers, the effects of interface curvature are relatively modest, with only a small increase in mobility in going from the 20 to 40 A diameter pore. Hydrogen bond population relaxation is nearly bulk-like in the core, but considerably slower in the interfacial region. PMID- 22070320 TI - Monte Carlo simulation on polymer translocation in crowded environment. AB - The effect of crowded environment with static obstacles on the translocation of a three-dimensional self-avoiding polymer through a small pore is studied using dynamic Monte Carlo simulation. The translocation time tau is dependent on polymer-obstacle interaction and obstacle concentration. The influence of obstacles on the polymer translocation is explained qualitatively by the free energy landscape. There exists a special polymer-obstacle interaction at which the translocation time is roughly independent of the obstacle concentration at low obstacle concentration, and the strength of the special interaction is roughly independent of chain length N. Scaling relation tau ~ N(1.25) is observed for strong driving translocations. The diffusion property of polymer chain is also influenced by obstacles. Normal diffusion is only observed in dilute solution without obstacles or in a crowded environment with weak polymer-obstacle attraction. Otherwise, subdiffusion behavior of polymer is observed. PMID- 22070321 TI - Phase behaviors of cyclic diblock copolymers. AB - A spectral method of self-consistent field theory has been applied to AB cyclic block copolymers. Phase behaviors of cyclic diblock copolymers, such as order disorder transition, order-order transition, and domain spacing size, have been studied, showing good consistency with previous experimental and theoretical results. Compared to linear diblocks, cyclic diblocks are harder to phase separate due to the topological constraint of the ring structure. A direct disorder-to-cylinder transition window is observed in the phase diagram, which is significantly different from the mean field phase diagram of linear diblock copolymers. The domain spacing size ratio between cyclic and linear diblock copolymers is typically close to 0.707, indicating in segregation that the cyclic polymer can be considered to be made up of linear diblocks with half of the original chain length. PMID- 22070322 TI - The condensation and ordering of models of empty liquids. AB - We consider a simple model consisting of particles with four bonding sites ("patches"), two of type A and two of type B, on the square lattice, and investigate its global phase behavior by simulations and theory. We set the interaction between B patches to zero and calculate the phase diagram as the ratio between the AB and the AA interactions, epsilon(AB)*, varies. In line with previous work, on three-dimensional off-lattice models, we show that the liquid vapor phase diagram exhibits a re-entrant or "pinched" shape for the same range of epsilon(AB)*, suggesting that the ratio of the energy scales--and the corresponding empty fluid regime--is independent of the dimensionality of the system and of the lattice structure. In addition, the model exhibits an order disorder transition that is ferromagnetic in the re-entrant regime. The use of low-dimensional lattice models allows the simulation of sufficiently large systems to establish the nature of the liquid-vapor critical points and to describe the structure of the liquid phase in the empty fluid regime, where the size of the "voids" increases as the temperature decreases. We have found that the liquid-vapor critical point is in the 2D Ising universality class, with a scaling region that decreases rapidly as the temperature decreases. The results of simulations and theoretical analysis suggest that the line of order-disorder transitions intersects the condensation line at a multi-critical point at zero temperature and density, for patchy particle models with a re-entrant, empty fluid, regime. PMID- 22070323 TI - Folding dynamics of Trp-cage in the presence of chemical interference and macromolecular crowding. I. AB - Proteins fold and function in the crowded environment of the cell's interior. In the recent years it has been well established that the so-called "macromolecular crowding" effect enhances the folding stability of proteins by destabilizing their unfolded states for selected proteins. On the other hand, chemical and thermal denaturation is often used in experiments as a tool to destabilize a protein by populating the unfolded states when probing its folding landscape and thermodynamic properties. However, little is known about the complicated effects of these synergistic perturbations acting on the kinetic properties of proteins, particularly when large structural fluctuations, such as protein folding, have been involved. In this study, we have first investigated the folding mechanism of Trp-cage dependent on urea concentration by coarse-grained molecular simulations where the impact of urea is implemented into an energy function of the side chain and/or backbone interactions derived from the all-atomistic molecular dynamics simulations with urea through a Boltzmann inversion method. In urea solution, the folding rates of a model miniprotein Trp-cage decrease and the folded state slightly swells due to a lack of contact formation between side chains at the terminal regions. In addition, the equilibrium m-values of Trp-cage from the computer simulations are in agreement with experimental measurements. We have further investigated the combined effects of urea denaturation and macromolecular crowding on Trp-cage's folding mechanism where crowding agents are modeled as hard-spheres. The enhancement of folding rates of Trp-cage is most pronounced by macromolecular crowding effect when the extended conformations of Trp-cast dominate at high urea concentration. Our study makes quantitatively testable predictions on protein folding dynamics in a complex environment involving both chemical denaturation and macromolecular crowding effects. PMID- 22070324 TI - Comparison of chemical and thermal protein denaturation by combination of computational and experimental approaches. II. AB - Chemical and thermal denaturation methods have been widely used to investigate folding processes of proteins in vitro. However, a molecular understanding of the relationship between these two perturbation methods is lacking. Here, we combined computational and experimental approaches to investigate denaturing effects on three structurally different proteins. We derived a linear relationship between thermal denaturation at temperature T(b) and chemical denaturation at another temperature T(u) using the stability change of a protein (DeltaG). For this, we related the dependence of DeltaG on temperature, in the Gibbs-Helmholtz equation, to that of DeltaG on urea concentration in the linear extrapolation method, assuming that there is a temperature pair from the urea (T(u)) and the aqueous (T(b)) ensembles that produces the same protein structures. We tested this relationship on apoazurin, cytochrome c, and apoflavodoxin using coarse-grained molecular simulations. We found a linear correlation between the temperature for a particular structural ensemble in the absence of urea, T(b), and the temperature of the same structural ensemble at a specific urea concentration, T(u). The in silico results agreed with in vitro far-UV circular dichroism data on apoazurin and cytochrome c. We conclude that chemical and thermal unfolding processes correlate in terms of thermodynamics and structural ensembles at most conditions; however, deviations were found at high concentrations of denaturant. PMID- 22070325 TI - Phase diagram of polypeptide chains. AB - We use a coarse grained protein model that enables us to determine the equilibrium phase diagram of natively folded alpha-helical and unfolded beta sheet forming peptides. The phase diagram shows that there are only two thermodynamically stable peptide phases, the peptide solution and the bulk fibrillar phase. In addition, it reveals the existence of various metastable peptide phases. The liquidlike oligomeric phases are metastable with respect to the fibrillar phases, and there is a hierarchy of metastability. The presented phase diagram provides a solid basis for understanding the assembly of polypeptide chains into the phases formed in their natively folded and unfolded conformations. PMID- 22070326 TI - Design and manufacture of combinatorial calcium phosphate bone scaffolds. AB - It is well known that pore design is an important determinant of both the quantity and distribution of regenerated bone in artificial bone tissue scaffolds. A requisite feature is that scaffolds must contain pore interconnections on the order of 100-1000 MUm (termed macroporosity). Within this range, there is not a definitive optimal interconnection size. Recent results suggest that pore interconnections permeating the scaffold build material on the order of 2-20 MUm (termed microporosity) drive bone growth into the macropore space at a faster rate and also provide a new space for bone growth, proliferating throughout the interconnected microporous network. The effects of microstructural features on bone growth has yet to be fully understood. This work presents the manufacture and characterization of novel combinatorial test scaffolds, scaffolds that test multiple microporosity and macroporosity designs within a single scaffold. Scaffolds such as this can efficiently evaluate multiple mechanical designs, with the advantage of having the designs colocated within a single defect site and therefore less susceptible to experimental variation. This paper provides the manufacturing platform, manufacturing control method, and demonstrates the manufacturing capabilities with three representative scaffolds. PMID- 22070327 TI - A fluid dynamics study in a 50 cc pulsatile ventricular assist device: influence of heart rate variability. AB - Although left ventricular assist devices (LVADs) have had success in supporting severe heart failure patients, thrombus formation within these devices still limits their long term use. Research has shown that thrombosis in the Penn State pulsatile LVAD, on a polyurethane blood sac, is largely a function of the underlying fluid mechanics and may be correlated to wall shear rates below 500 s( 1). Given the large range of heart rate and systolic durations employed, in vivo it is useful to study the fluid mechanics of pulsatile LVADs under these conditions. Particle image velocimetry (PIV) was used to capture planar flow in the pump body of a Penn State 50 cubic centimeters (cc) LVAD for heart rates of 75-150 bpm and respective systolic durations of 38-50%. Shear rates were calculated along the lower device wall with attention given to the uncertainty of the shear rate measurement as a function of pixel magnification. Spatial and temporal shear rate changes associated with data collection frequency were also investigated. The accuracy of the shear rate calculation improved by approximately 40% as the resolution increased from 35 to 12 MUm/pixel. In addition, data collection in 10 ms, rather than 50 ms, intervals was found to be preferable. Increasing heart rate and systolic duration showed little change in wall shear rate patterns, with wall shear rate magnitude scaling by approximately the kinematic viscosity divided by the square of the average inlet velocity, which is essentially half the friction coefficient. Changes in in vivo operating conditions strongly influence wall shear rates within our device, and likely play a significant role in thrombus deposition. Refinement of PIV techniques at higher magnifications can be useful in moving towards better prediction of thrombosis in LVADs. PMID- 22070328 TI - Cardiac assist with a twist: apical torsion as a means to improve failing heart function. AB - Changes in muscle fiber orientation across the wall of the left ventricle (LV) cause the apex of the heart to turn 10-15 deg in opposition to its base during systole and are believed to increase stroke volume and lower wall stress in healthy hearts. Studies show that cardiac torsion is sensitive to various disease states, which suggests that it may be an important aspect of cardiac function. Modern imaging techniques have sparked renewed interest in cardiac torsion dynamics, but no work has been done to determine whether mechanically augmented apical torsion can be used to restore function to failing hearts. In this report, we discuss the potential advantages of this approach and present evidence that turning the cardiac apex by mechanical means can displace a clinically significant volume of blood from failing hearts. Computational models of normal and reduced-function LVs were created to predict the effects of applied apical torsion on ventricular stroke work and wall stress. These same conditions were reproduced in anesthetized pigs with drug-induced heart failure using a custom apical torsion device programmed to rotate over various angles during cardiac systole. Simulations of applied 90 deg torsion in a prolate spheroidal computational model of a reduced-function pig heart produced significant increases in stroke work (25%) and stroke volume with reduced fiber stress in the epicardial region. These calculations were in substantial agreement with corresponding in vivo measurements. Specifically, the computer model predicted torsion-induced stroke volume increases from 13.1 to 14.4 mL (9.9%) while actual stroke volume in a pig heart of similar size and degree of dysfunction increased from 11.1 to 13.0 mL (17.1%). Likewise, peak LV pressures in the computer model rose from 85 to 95 mm Hg (11.7%) with torsion while maximum ventricular pressures in vivo increased in similar proportion, from 55 to 61 mm Hg (10.9%). These data suggest that: (a) the computer model of apical torsion developed for this work is a fair and accurate predictor of experimental outcomes, and (b) supra-physiologic apical torsion may be a viable means to boost cardiac output while avoiding blood contact that occurs with other assist methods. PMID- 22070329 TI - MRI-based modeling for radiocarpal joint mechanics: validation criteria and results for four specimen-specific models. AB - The objective of this study was to validate the MRI-based joint contact modeling methodology in the radiocarpal joints by comparison of model results with invasive specimen-specific radiocarpal contact measurements from four cadaver experiments. We used a single validation criterion for multiple outcome measures to characterize the utility and overall validity of the modeling approach. For each experiment, a Pressurex film and a Tekscan sensor were sequentially placed into the radiocarpal joints during simulated grasp. Computer models were constructed based on MRI visualization of the cadaver specimens without load. Images were also acquired during the loaded configuration used with the direct experimental measurements. Geometric surface models of the radius, scaphoid and lunate (including cartilage) were constructed from the images acquired without the load. The carpal bone motions from the unloaded state to the loaded state were determined using a series of 3D image registrations. Cartilage thickness was assumed uniform at 1.0 mm with an effective compressive modulus of 4 MPa. Validation was based on experimental versus model contact area, contact force, average contact pressure and peak contact pressure for the radioscaphoid and radiolunate articulations. Contact area was also measured directly from images acquired under load and compared to the experimental and model data. Qualitatively, there was good correspondence between the MRI-based model data and experimental data, with consistent relative size, shape and location of radioscaphoid and radiolunate contact regions. Quantitative data from the model generally compared well with the experimental data for all specimens. Contact area from the MRI-based model was very similar to the contact area measured directly from the images. For all outcome measures except average and peak pressures, at least two specimen models met the validation criteria with respect to experimental measurements for both articulations. Only the model for one specimen met the validation criteria for average and peak pressure of both articulations; however the experimental measures for peak pressure also exhibited high variability. MRI-based modeling can reliably be used for evaluating the contact area and contact force with similar confidence as in currently available experimental techniques. Average contact pressure, and peak contact pressure were more variable from all measurement techniques, and these measures from MRI-based modeling should be used with some caution. PMID- 22070331 TI - The effect of boundary condition on the biomechanics of a human pelvic joint under an axial compressive load: a three-dimensional finite element model. AB - The finite element (FE) model of the pelvic joint is helpful for clinical diagnosis and treatment of pelvic injuries. However, the effect of an FE model boundary condition on the biomechanical behavior of a pelvic joint has not been well studied. The objective of this study was to study the effect of boundary condition on the pelvic biomechanics predictions. A 3D FE model of a pelvis using subject-specific estimates of intact bone structures, main ligaments and bone material anisotropy by computed tomography (CT) gray value was developed and validated by bone surface strains obtained from rosette strain gauges in an in vitro pelvic experiment. Then three FE pelvic models were constructed to analyze the effect of boundary condition, corresponding to an intact pelvic joint, a pelvic joint without sacroiliac ligaments and a pelvic joint without proximal femurs, respectively. Vertical load was applied to the same pelvis with a fixed prosthetic femoral stem and the same load was simulated in the FE model. A strong correlation coefficient (R(2)=0.9657) was calculated, which indicated a strong correlation between the FE analysis and experimental results. The effect of boundary condition changes on the biomechanical response depended on the anatomical location and structure of the pelvic joint. It was found that acetabulum fixed in all directions with the femur removed can increase the stress distribution on the acetabular inner plate (approximately double the original values) and decrease that on the superior of pubis (from 7 MPa to 0.6 MPa). Taking sacrum and ilium as a whole, instead of sacroiliac and iliolumber ligaments, can influence the stress distribution on ilium and pubis bone vastly. These findings suggest pelvic biomechanics is very dependent on the boundary condition in the FE model. PMID- 22070330 TI - Multi-rigid image segmentation and registration for the analysis of joint motion from three-dimensional magnetic resonance imaging. AB - We report an image segmentation and registration method for studying joint morphology and kinematics from in vivo magnetic resonance imaging (MRI) scans and its application to the analysis of foot and ankle joint motion. Using an MRI compatible positioning device, a foot was scanned in a single neutral and seven other positions ranging from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. A segmentation method combining graph cuts and level set was developed. In the subsequent registration step, a separate rigid body transformation for each bone was obtained by registering the neutral position dataset to each of the other ones, which produced an accurate description of the motion between them. The segmentation algorithm allowed a user to interactively delineate 14 foot bones in the neutral position volume in less than 30 min total (user and computer processing unit [CPU]) time. Registration to the seven other positions took approximately 10 additional minutes of user time and 5.25 h of CPU time. For validation, our results were compared with those obtained from 3DViewnix, a semiautomatic segmentation program. We achieved excellent agreement, with volume overlap ratios greater than 88% for all bones excluding the intermediate cuneiform and the lesser metatarsals. For the registration of the neutral scan to the seven other positions, the average overlap ratio is 94.25%, while the minimum overlap ratio is 89.49% for the tibia between the neutral position and position 1, which might be due to different fields of view (FOV). To process a single foot in eight positions, our tool requires only minimal user interaction time (less than 30 min total), a level of improvement that has the potential to make joint motion analysis from MRI practical in research and clinical applications. PMID- 22070332 TI - Calibration of hyperelastic material properties of the human lumbar intervertebral disc under fast dynamic compressive loads. AB - Under fast dynamic loading conditions (e.g. high-energy impact), the load rate dependency of the intervertebral disc (IVD) material properties may play a crucial role in the biomechanics of spinal trauma. However, most finite element models (FEM) of dynamic spinal trauma uses material properties derived from quasi static experiments, thus neglecting this load rate dependency. The aim of this study was to identify hyperelastic material properties that ensure a more biofidelic simulation of the IVD under a fast dynamic compressive load. A hyperelastic material law based on a first-order Mooney-Rivlin formulation was implemented in a detailed FEM of a L2-L3 functional spinal unit (FSU) to represent the mechanical behavior of the IVD. Bony structures were modeled using an elasto-plastic Johnson-Cook material law that simulates bone fracture while ligaments were governed by a viscoelastic material law. To mimic experimental studies performed in fast dynamic compression, a compressive loading velocity of 1 m/s was applied to the superior half of L2, while the inferior half of L3 was fixed. An exploratory technique was used to simulate dynamic compression of the FSU using 34 sets of hyperelastic material constants randomly selected using an optimal Latin hypercube algorithm and a set of material constants derived from quasi-static experiments. Selection or rejection of the sets of material constants was based on compressive stiffness and failure parameters criteria measured experimentally. The two simulations performed with calibrated hyperelastic constants resulted in nonlinear load-displacement curves with compressive stiffness (7335 and 7079 N/mm), load (12,488 and 12,473 N), displacement (1.95 and 2.09 mm) and energy at failure (13.5 and 14.7 J) in agreement with experimental results (6551 +/- 2017 N/mm, 12,411 +/- 829 N, 2.1 +/ 0.2 mm and 13.0 +/- 1.5 J respectively). The fracture pattern and location also agreed with experimental results. The simulation performed with constants derived from quasi-static experiments showed a failure energy (13.2 J) and a fracture pattern and location in agreement with experimental results, but a compressive stiffness (1580 N/mm), a failure load (5976 N) and a displacement to failure (4.8 mm) outside the experimental corridors. The proposed method offers an innovative way to calibrate the hyperelastic material properties of the IVD and to offer a more realistic simulation of the FSU in fast dynamic compression. PMID- 22070333 TI - A device to study the effects of stretch gradients on cell behavior. AB - Mechanical forces are key regulators of cell function with varying loads capable of modulating behaviors such as alignment, migration, phenotype modulation, and others. Historically, cell-stretching experiments have employed mechanically simple environments (e.g., uniform uniaxial or equibiaxial stretches). However, stretch distributions in vivo can be highly non-uniform, particularly in cases of disease or subsequent to interventional treatments. Herein, we present a cell stretching device capable of subjecting cells to controllable gradients in biaxial stretch via radial deformation of circular elastomeric membranes. By including either a defect or a rigid fixation at the center of the membrane, various gradients are generated. Capabilities of the device were quantified by tracking marked positions of the membrane while applying various loads, and experimental feasibility was assessed by conducting preliminary experiments with 3T3 fibroblasts and 10T1/2 cells subjected to 24 h of cyclic stretch. Quantitative real-time PCR was used to measure changes in mRNA expression of a profile of genes representing the major smooth muscle phenotypes. Genes associated with the contractile state were both upregulated (e.g., calponin) and downregulated (e.g., alpha-2-actin), and genes associated with the synthetic state were likewise both upregulated (e.g., SKI-like oncogene) and downregulated (e.g., collagen III). In addition, cells aligned with an orientation perpendicular to the maximal stretch direction. We have developed an in vitro cell culture device that can produce non-uniform stretch environments similar to in vivo mechanics. Cells stretched with this device showed alignment and altered mRNA expression indicative of phenotype modulation. Understanding these processes as they relate to in vivo pathologies could enable a more accurately targeted treatment to heal or inhibit disease, either through implantable device design or pharmaceutical approaches. PMID- 22070334 TI - Elasticity of human embryonic stem cells as determined by atomic force microscopy. AB - The expansive growth and differentiation potential of human embryonic stem cells (hESCs) make them a promising source of cells for regenerative medicine. However, this promise is off set by the propensity for spontaneous or uncontrolled differentiation to result in heterogeneous cell populations. Cell elasticity has recently been shown to characterize particular cell phenotypes, with undifferentiated and differentiated cells sometimes showing significant differences in their elasticities. In this study, we determined the Young's modulus of hESCs by atomic force microscopy using a pyramidal tip. Using this method we are able to take point measurements of elasticity at multiple locations on a single cell, allowing local variations due to cell structure to be identified. We found considerable differences in the elasticity of the analyzed hESCs, reflected by a broad range of Young's modulus (0.05-10 kPa). This surprisingly high variation suggests that elasticity could serve as the basis of a simple and efficient large scale purification/separation technique to discriminate subpopulations of hESCs. PMID- 22070335 TI - The association of wall mechanics and morphology: a case study of abdominal aortic aneurysm growth. AB - The purpose of this study is to evaluate the potential correlation between peak wall stress (PWS) and abdominal aortic aneurysm (AAA) morphology and how it relates to aneurysm rupture potential. Using in-house segmentation and meshing software, six 3-dimensional (3D) AAA models from a single patient followed for 28 months were generated for finite element analysis. For the AAA wall, both isotropic and anisotropic materials were used, while an isotropic material was used for the intraluminal thrombus (ILT). These models were also used to calculate 36 geometric indices characteristic of the aneurysm morphology. Using least squares regression, seven significant geometric features (p < 0.05) were found to characterize the AAA morphology during the surveillance period. By means of nonlinear regression, PWS estimated with the anisotropic material was found to be highly correlated with three of these features: maximum diameter (r = 0.992, p = 0.002), sac volume (r = 0.989, p = 0.003) and diameter to diameter ratio (r = 0.947, p = 0.033). The correlation of wall mechanics with geometry is nonlinear and reveals that PWS does not increase concomitantly with aneurysm diameter. This suggests that a quantitative characterization of AAA morphology may be advantageous in assessing rupture risk. PMID- 22070337 TI - A novel sensor concept for optimization of loosening diagnostics in total hip replacement. AB - The main reason for the revision of total hip replacements is aseptic loosening, caused by stress shielding and wear particle induced osteolysis. In order to detect an implant loosening early, the osseointegration of endoprosthetic implants must be measured exactly. Currently applied diagnostic methods, such as standard radiographs and clinical symptomatology, often result in an imprecise diagnosis. A novel radiation-free method to improve the diagnostic investigation of implant loosening is presented. The osseointegration of an implant can be identified using mechanical magnetic sensors (oscillators), which impinge on small membranes inside an implant component, e.g., the femoral hip stem. The maximum velocity after impingement of the oscillator depends on the osseointegration of the implant. Excitation of the oscillator is realized by a coil outside the human body. Another external coil is used to detect the velocity of the oscillator. To demonstrate the principle of the novel loosening sensor, an overdimensioned test device was designed to measure simulated loosening phases in the first experimental tests with different material layers. The overdimensioned test device of the loosening sensor showed significant differences in the various phases of fixation. Analysis of the membrane without any material layer in the case of advanced loosening resulted in a 23% higher maximum velocity compared to an attached artificial bone layer. Based on these preliminary results, the sensor system shows potential for the detection of implant loosening. Moreover, the proposed system could be used in experimental applications to determine the quality of bioactive coatings and new implant materials. PMID- 22070336 TI - Evaluating foot kinematics using magnetic resonance imaging: from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. AB - The foot consists of many small bones with complicated joints that guide and limit motion. A variety of invasive and noninvasive means [mechanical, X-ray stereophotogrammetry, electromagnetic sensors, retro-reflective motion analysis, computer tomography (CT), and magnetic resonance imaging (MRI)] have been used to quantify foot bone motion. In the current study we used a foot plate with an electromagnetic sensor to determine an individual subject's foot end range of motion (ROM) from maximum plantar flexion, internal rotation, and inversion to maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. We then used a custom built MRI compatible device to hold each subject's foot during scanning in eight unique positions determined from the end ROM data. The scan data were processed using software that allowed the bones to be segmented with the foot in the neutral position and the bones in the other seven positions to be registered to their base positions with minimal user intervention. Bone to bone motion was quantified using finite helical axes (FHA). FHA for the talocrural, talocalcaneal, and talonavicular joints compared well to published studies, which used a variety of technologies and input motions. This study describes a method for quantifying foot bone motion from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation with relatively little user processing time. PMID- 22070338 TI - Theory of the short time mechanical relaxation in articular cartilage. AB - Articular cartilage is comprised of macromolecules, proteoglycans, with (charged) chondroitin sulfate side-chains attached to them. The proteoglycans are attached to longer hyaluronic acid chains, trapped within a network of type II collagen fibrils. As a consequence of their relatively long persistence lengths, the number of persistence lengths along the chondroitin sulfate and proteoglycan chains is relatively small, and consequently, the retraction times for these side chains are also quite short. We argue that, as a consequence of this, they will not significantly inhibit the reptation of the hyaluronic acid chains. Scaling arguments applied to this model allow us to show that the shortest of the mechanical relaxation times of cartilage, that have been determined by Fyhrie and Barone to be due to reptation of the hyaluronic acid polymers, should have a dependence on the load, i.e., force per unit interface area P, carried by the cartilage, proportional to P(3/2). PMID- 22070340 TI - Qualitative and quantitative analysis of crystallographic defects present in 2D colloidal sphere arrays. AB - In this work, we present a study of the typical spontaneous defects present in self-assembled colloidal monolayers grown from polystyrene and silica microspheres. The quality of two-dimensional crystals from different colloidal suspensions of beads around 1 MUm in diameter has been studied qualitatively and quantitatively, evaluated in 2D hexagonal arrays at different scales through Fourier analysis of SEM images and optical characterization. The crystallographic defects are identified to better understand their origin and their effects on the crystal quality, as well as to find the best conditions colloidal suspensions must fulfill to achieve optimal quality samples. PMID- 22070341 TI - Voriconazole serum levels measured by high-performance liquid chromatography: a monocentric study in treated patients. AB - In this study we present the results of a therapeutic drug monitoring retrospective analysis involving 14 patients with several underlying diseases who were receiving voriconazole for the treatment of fungal infections. A simple high performance liquid chromatography assay with ultraviolet detection was used in the drug monitoring. We report here that serum concentrations were highly variable and unpredictable in most patients. We also found that lack of response was more frequent in patients with levels persistently lower than 1 mg/l. The number of samples with voriconazole concentrations below 1 mg/l was significantly higher in patients who exhibited therapeutic failures (88% versus 27%; P < 0.001). In addition, the period of time in which voriconazole concentrations were maintained below 1 mg/l was slightly higher in patients in the failure group. We suggest that serum concentration should be individually quantified for patients receiving voriconazole therapy. Further prospective studies are needed to clarify the potential benefit of the individualization of treatment. PMID- 22070342 TI - Gestational diabetes and pre-pregnancy overweight: possible factors involved in newborn macrosomia. AB - AIM: Good glycemic control in gestational diabetes mellitus (GDM) seems not to be enough to prevent macrosomia (large-for-gestational-age newborns). In GDM pregnancies we studied the effects of glycemic control (as glycosylated hemoglobin [HbA1c]), pre-pregnancy body mass index (PP-BMI) and gestational weight gain per week (GWG-W) on the frequency of macrosomia. METHODS: We studied 251 GDM pregnancies, divided into two groups: PP-BMI<25.0kg/m(2) (the non overweight group; n=125), and PP-BMI>=25.0kg/m(2) (the overweight group; n=126). A newborn weight Z-score>1.28 was considered large-for-gestational-age. Statistical analysis was carried out using the Student's t-test and chi(2) -test, receiver-operator characteristic curves and linear and binary logistic regressions. RESULTS: Prevalence of macrosomia was 14.9% among GDM (n=202/251, 88.4%) with good glycemic control (mean HbA1c<6.0%), and 28.1% in those with mean HbA1c>=6.0% (n=49/251, P<0.025). Macrosomia rates were 10.4% in the non overweight group and 24.6% in the overweight group (P=0.00308), notwithstanding both having similar mean HbA1c (5.48+/-0.065 and 5.65+/-0.079%, P=0.269), and similar GWG-W (0.292+/-0.017 and 0.240+/-0.021kg/week, P=0.077). Binary logistic regressions showed that PP-BMI (P=0.012) and mean HbA1c (P=0.048), but not GWG-W (P=0.477), explained macrosomia. CONCLUSIONS: Good glycemic control in GDM patients was not enough to reduce macrosomia to acceptable limits (<10% of newborns). PP-BMI and mean HbA1c (but not GWG-W) were significant predictors of macrosomia. Thus, without ceasing in our efforts to improve glycemic control during GDM pregnancies, patients with overweight/obesity need to be treated prior to becoming pregnant. PMID- 22070344 TI - Functional detection of proteins by caged aptamers. AB - While many diagnostic assay platforms enable the measurement of analytes with high sensitivity, most of them result in a disruption of the analyte's native structure and, thus, in loss of function. Consequently, the analyte can be used neither for further analytical assessment nor functional analysis. Herein we report the use of caged aptamers as templates during apta-PCR analysis of targets. Aptamers are short nucleic acids that fold into a well-defined three dimensional structure in which they interact with target molecules with high affinity and specificity. Nucleic acid aptamers can also serve as templates for qPCR approaches and, thus, have been used as high affinity ligands to bind to target molecules and subsequently for quantification by qPCR, an assay format coined apta-PCR. Caged aptamers in turn refer to variants that bear one or more photolabile groups at strategic positions. The activity of caged aptamers can thus be turned on or off by light irradiation. The latter allows the mild elution of target-bound aptamers while the target's native structure and function remain intact. We demonstrate that this approach allows the quantitative and subsequently the functional assessment of analytes. Since caged aptamers can be generated emanating from virtually every available aptamer, the described approach can be generalized and adopted to any target-aptamer pair and, thus, have a broad applicability in proteomics and clinical diagnostics. PMID- 22070345 TI - Predictors of the depressive symptomatology of the family caregivers of Chinese stroke patients in Hong Kong. AB - The aim of this cross-sectional study was to determine the socio-demographic and clinical factors associated with depressive symptoms in the family caregivers of Hong Kong Chinese stroke patients. One hundred and twenty-three patients at a stroke clinic and their family caregivers formed the study sample. The depressive symptoms of both the patients and their family caregivers were rated with the Chinese version of the 15-item Geriatric Depression Scale (GDS). Participants' socio-demographic data and clinical characteristics served as the independent variables in relation to the caregivers' GDS scores. Patients' and caregivers' somatic and psychological conditions were measured with 10 scales. In univariate analysis, caregivers' GDS scores were significantly correlated with certain of their characteristics [Modified Life Event Scale (MLES), Cumulative Illness Rating Scale (CIRS) and Lubben Social Network Scale (LSNS) scores, sex and being a housewife] and those of the patients (GDS score and being a housewife). Multiple regression analysis showed caregivers' MLES and CIRS scores and patients' GDS scores to be independent correlates of caregivers' GDS scores. Adverse events encountered by caregivers in the past 6 months, their current health problems and patients' depressive symptoms were found to be the principal factors associated with caregivers' depressive symptoms. PMID- 22070346 TI - Drinking to our health: can beverage companies cut calories while maintaining profits? AB - Carbonated soft drinks and other beverages make up an increasing percentage of energy intake, and there are rising public health concerns about the links between consumption of sugar-sweetened beverages and weight gain, obesity, and other cardiometabolic problems. In response, the food and beverage industry claims to be reformulating products, reducing package or portion sizes and introducing healthier options. Comparative analysis on various changes and their potential effects on public health are needed. We conduct a case study using the two largest and most influential producers of sweetened beverages, The Coca-Cola Company and PepsiCo Inc., who together control 34% of the global soft drink market, examining their product portfolios globally and in three critical markets (the United States, Brazil and China) from 2000 to 2010. On a global basis, total revenues and energy per capita sold increased, yet the average energy density (kJ 100 mL(-1) ) sold declined slightly, suggesting a shift to lower-calorie products. In the United States, both total energy per capita and average energy density of beverages sold decreased, while the opposite was true in the developing markets of Brazil and China, with total per capita energy increasing greatly in China and, to a lesser extent, in Brazil. PMID- 22070347 TI - Irish psychiatric nurses' self-reported sources of knowledge for practice. AB - Evidence-based practice (EBP) is an approach to health care in which health professionals use the best evidence available to guide their clinical decisions and practice. Evidence is drawn from a range of sources, including published research, educational content and practical experience. This paper reports the findings of a study that investigated the sources of knowledge or evidence for practice used by psychiatric nurses in Ireland. The paper is part of a larger study, which also investigated barriers, facilitators and level of skills in achieving EBP among Irish psychiatric nurses. Data were collected in a postal survey of a random sample of Irish psychiatric nurses using the Development of Evidence-Based Practice Questionnaire. The findings revealed that the majority of survey respondents based their practice on information which was derived from interactions with patients, from their personal experience and from information shared by colleagues and members of the multidisciplinary team, in preference to published sources of empirically derived evidence. These findings are consistent with those of the previous similar studies among general nurses and suggest that Irish psychiatric nurses face similar challenges to their general nursing counterparts in attaining of EBP. PMID- 22070348 TI - Apocynin attenuates oxidative stress and hypertension in young spontaneously hypertensive rats independent of ADMA/NO pathway. AB - Both NADPH oxidase-derived reactive oxygen species (ROS) and asymmetric dimethylarginine (ADMA) are increased in hypertension. Apocynin, an NADPH oxidase inhibitor, could inhibit ROS, thus we tested whether apocynin can block NADPH oxidase and prevent increases of ADMA and blood pressure (BP) in spontaneously hypertensive rats (SHRs). SHRs and Wistar Kyoto (WKY) rats, aged 4 weeks, were assigned to four groups: untreated SHRs and WKY rats, SHRs and WKY rats that received 2.5 mM apocynin for 8 weeks. BP was significantly higher in SHRs compared to WKY rats, which was attenuated by apocynin. Apocynin prevented p47phox translocation in SHR kidneys, but not the increase of superoxide and H(2)O(2). Additionally, apocynin did not protect SHRs against increased ADMA. Apocynin blocks NADPH oxidase to attenuate hypertension, but has little effect on the ADMA/nitric oxide (NO) pathway in young SHRs. The reduction of ROS and the preservation of NO simultaneously might be a better approach to restoring ROS-NO balance to prevent hypertension. PMID- 22070349 TI - Trueness in the measurement of haemoglobin: consensus or reference method? AB - BACKGROUND: For the measurement of haemoglobin a reference method exists: the haemiglobincyanide method. However, a Dutch external quality assessment organization does not use this method in the evaluation of trueness of results. The aim of this work was to assess whether trueness was compromised by the use of a consensus value. METHODS: Five Cell Dyn Sapphires (Abbott) in three independent locations were used to measure haemoglobin concentration. Results were compared to the reference method (haemiglobincyanide). Patient samples with a distribution over clinically relevant concentrations (Hb 2.5-10.2 mmol/L) were used next to samples from external quality assessment rounds. Passing and Bablok regression analysis and Bland-Altman plots were used to evaluate any systematic deviation. RESULTS: Results measured on the Cell Dyn Sapphires deviated significantly from the results obtained with the reference method. Remarkably, consensus results from external quality control samples also deviated significantly from the reference method. CONCLUSIONS: A significant negative bias exists in the measurement of haemoglobin on Cell Dyn Sapphires. Additionally, the consensus value as reported in external quality control assessment also shows an even greater significant negative bias compared to the reference method. As a reference method is available, external quality assessment would benefit from using this method instead of a consensus value to evaluate trueness. PMID- 22070350 TI - Speed of sample transportation by a pneumatic tube system can influence the degree of hemolysis. AB - BACKGROUND: The objective of the study was to find the incidence of hemolysis in samples transported through a pneumatic tube system (PTS) at different speeds. METHODS: This prospective observational study was done in three phases: "short distance and high speed (115 m at 3 m/s)", "long distance and high speed (225 m at 3 m/s)" and "short distance and slow speed (115 at 2 m/s)". Fifty-two, 215 and 45 serum tube pairs, respectively, were evaluated in these three phases. A set of tubes was sent by PTS while the other was hand-carried. Samples were analyzed for supernatant hemoglobin (Hb), potassium (K+) and lactate dehydrogenase (LD). RESULTS: Mean transit time of samples through the PTS was much shorter as compared to human courier in all three phases. LD was elevated in PTS arm in the "short distance and high speed" phase and in the "long distance and high speed" phase, all three indices of hemolysis - Hb, K+ and LD - showed elevation in the PTS arm. However, at "short distance and slow speed" phase, there was no hemolysis in the PTS arm. CONCLUSIONS: Hospitals should validate their PTS before use and, by altering speed of sample transportation, hemolysis may be obliterated. PMID- 22070351 TI - False-positive calcitonin results in patients with benign goiter. PMID- 22070353 TI - Developmental plasticity, morphological variation and evolvability: a multilevel analysis of morphometric integration in the shape of compound leaves. AB - The structure of compound leaves provides flexibility for morphological change by variation in the shapes, sizes and arrangement of leaflets. Here, we conduct a multilevel analysis of shape variation in compound leaves to explore the developmental plasticity and evolutionary potential that are the basis of diversification in leaf shape. We use the methods of geometric morphometrics to study the shapes of individual leaflets and whole leaves in 20 taxa of Potentilla (sensu lato). A newly developed test based on the bootstrap approach suggests that uncertainty in the molecular phylogeny precludes firm conclusions whether there is a phylogenetic signal in the data on leaf shape. For variation among taxa, variation within taxa, as well as fluctuating asymmetry, there is evidence of strong morphological integration. The patterns of variation are similar across all three levels, suggesting that integration within taxa may act as a constraint on evolutionary change. PMID- 22070352 TI - Continuous apple consumption induces oral tolerance in birch-pollen-associated apple allergy. AB - BACKGROUND: Patients with birch pollen allergy (major allergen: Bet v 1) have often an associated oral allergy syndrome (OAS) to apple, which contains the cross-reactive allergen Mal d 1. As successful birch pollen immunotherapy does not consistently improve apple related OAS symptoms, we evaluated whether regular apple consumption has an effect on OAS and immune parameters of Mal d 1 or Bet v 1 allergy. METHODS: A total of 40 patients with a clear history of birch pollen rhinoconjunctivitis and associated OAS to apple were included in an open, randomized, controlled clinical trial: 27 patients consumed daily defined amount of apple (1-128 g), doubling the amount every two to three weeks, while 13 patients remained untreated. Primary endpoint was the proportion of patients that achieved tolerance to at least 128 g of apple at the end of the study after 8 months. Exploratory endpoints were questionnaire about cross-reactive food and pollen allergy symptoms, conjunctival provocation test with birch pollen and Bet v 1, and in vitro tests (tIgE, sIgE, and IgG4 to Mal d 1 and Bet v 1; basophil activation test with both allergens). RESULTS: Seventeen of 27 patients in active group and none of 13 patients in control group (P = 0.0001) could tolerate a whole apple after the intervention. However, differences in endpoints reflecting systemic immune reactivity did not reach statistical significance. CONCLUSION: In patients with OAS to apple, tolerance can be safely induced with slowly, gradually increasing consumption of apple. However, the observation of a relapse after discounting of apple consumption and absence of immunologic changes suggest that induced tolerance is only transient. PMID- 22070354 TI - Overcoming sequelae of childhood sexual abuse with stress management. AB - The immense stress associated with experiencing and surviving childhood sexual abuse directly influences coping, immune function and overall health. Lifelong overuse of maladaptive coping strategies results in impaired adjustment to stress. The purpose of this research was to re-examine if stress management education would be effective in improving coping skills for this population. Two 4-week series of stress management workshops were completed by 32 adult survivors who completed the ways of coping questionnaire before and after the training. Four categories of coping showed significant change. Stress management education is an effective and cost-efficient approach that gives adult survivors an empowering set of tools for their healing journey. PMID- 22070355 TI - Views of patients and general dental practitioners on the organizational aspects of a general dental practice. AB - OBJECTIVE: To examine the views of patients and general dental practitioners (GDPs) on the organizational aspects of a general dental practice and to see whether their views differ. BACKGROUND: Health care has increasingly centred on the patient over the last two decades, and the patients' opinions have been taken more seriously. Although in other health-care sectors research on organizational aspects has been performed, research in dental care is lacking on this subject. DESIGN: We developed two questionnaires covering 41 organizational aspects of a general dental practice: one for GDPs and one for dental patients. The questionnaires were handed out in dental practices to 5000 patients and sent to 500 GDPs. RESULTS: We describe the results of the organizational aspects mentioned most by 25% of the dental patients. For most aspects, the views of the patients and GDPs differed significantly. However, both respondent groups mentioned the same category the most. CONCLUSIONS: The results of this study could be used on a policy level for the development of guidelines and on a practice level for individual GDPs to adjust practice management to the preferences of patients. PMID- 22070356 TI - Cytochrome P450-catalysed reactive oxygen species production mediates the ( )schisandrin B-induced glutathione and heat shock responses in AML12 hepatocytes. AB - Sch B (schisandrin B), the most abundant dibenzocyclooctadiene lignan in Fructus schisandrae, can induce glutathione antioxidant and heat shock responses, as well as protect against oxidant-induced injury in various tissues, including the liver in rodents and AML12 (alpha mouse liver 12) hepatocytes. (-)Sch B is the most potent stereoisomer of Sch B in its cytoprotective action on AML12 hepatocytes. To define the role of ROS (reactive oxygen species) arising from CYP (cytochrome P450)-catalysed metabolism of (-)Sch B in triggering glutathione antioxidant and heat shock responses, the effects of a CYP inhibitor [ABT (aminobenzotriazole)] and antioxidants [DMTU (dimethylthiouracil) and TRX (trolox)] on (-)Sch B-induced ROS production and associated increases in cellular GSH level, as well as Hsp25/70 (heat-shock protein 25/70) production, were investigated in AML12 hepatocytes. The results indicated that (-)Sch B causes a dose dependent and sustained increase in ROS production over 6 h in AML12 hepatocytes, which was completely suppressed by pre-/co-treatment with ABT or DTMU/TRX. Incubation with (-)Sch B for 6 h caused optimal and dose-dependent increases in cellular GSH level and Hsp25/70 production at 16 h post-drug exposure in AML12 hepatocytes. These cellular responses were associated with protection against menadione induced apoptosis. Pre-/co-treatment with ABT or antioxidants completely abrogated the (-)Sch B-induced glutathione antioxidant and heat shock responses, as well as protection against menadione-induced apoptosis. Experimental evidence obtained thus far supports the causal role of ROS arising from the CYP-catalysed metabolism of (-)Sch B in eliciting glutathione antioxidant and heat shock responses in AML12 hepatocytes. PMID- 22070357 TI - Effect of acute posttrauma propranolol on PTSD outcome and physiological responses during script-driven imagery. AB - INTRODUCTION: Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the beta-adrenergic blocker propranolol, to reduce this overconsolidation. AIMS: In this randomized, placebo-controlled study of the efficacy of propranolol in reducing the development of PTSD, we optimized dosages and conducted both psychophysiological and clinical assessments 1 and 3 months after the traumatic event. Forty-one emergency department patients who had experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo for 19 days. At 4 and 12 weeks post trauma, PTSD symptoms were assessed. One week later, participants engaged in script-driven imagery of their traumatic event while psychophysiological responses were measured. RESULTS: Physiological reactivity during script-driven traumatic imagery, severity of PTSD symptoms, and the rate of the PTSD diagnostic outcome were not significantly different between the two groups. However, post hoc subgroup analyses showed that in participants with high drug adherence, at the 5-week posttrauma assessment, physiological reactivity was significantly lower during script-driven imagery in the propranolol than in the placebo subjects. CONCLUSIONS: The physiological results provide some limited support for a model of PTSD in which a traumatic conditioned response is reduced by posttrauma propranolol. However, the clinical results from this study do not support the preventive use of propranolol in the acute aftermath of a traumatic event. PMID- 22070358 TI - Medical problems and oral care of patients with Down syndrome: a literature review. AB - When planning the dental treatment of patients with Down syndrome (DS), dental practitioners should always consider their general health, in order to achieve a holistic and interdisciplinary approach. This article presents a literature review of the primary medical conditions in patients with DS that may affect their general health care and the appropriate clinical delivery of oral health care. PMID- 22070359 TI - The involvement of Iowa dentists in hospice care. AB - The relationships between dentist characteristics and professional education with involvement of Iowa dentists in hospice care were investigated. Using the 1999 Iowa Health Professional database, a survey requesting information regarding involvement in and training for care of hospice patients was mailed to all licensed dentists (N = 1,210). Two mailings yielded a 54.6% response rate. Of the 638 dentist respondents, the mean age was 47, 86% were male, 88% general dentists, and 295 (46%) reported providing some treatment for hospice patients. At least one dentist reported providing hospice patient care in 72 of Iowa's 99 counties. About 90% of dentists treating hospice patients were general practitioners. Males were more likely to provide treatment (p < 0.0313). Neither dentist age nor years in practice were significant predictors. Dentists were more likely to treat hospice patients in the office (IO, 40%). The most prevalent treatments were denture relines (31% IO; 71% OO), examinations (16% IO; 68% OO), and emergency treatment (12.5% IO; 53% OO). More than 86% of surveyed dentists indicated that their professional education did not adequately train them to meet the clinical, psychosocial, communication, or spiritual needs of hospice patients. PMID- 22070360 TI - The incidence of dental caries in children and adolescents who have cerebral palsy and are participating in a dental program in Brazil. AB - The aim of this study was to describe the incidence of caries among children and adolescents who have cerebral palsy. The authors conducted baseline and follow-up dental examinations of 118 children and adolescents with cerebral palsy in a specialized healthcare unit in Sao Paulo, Brazil. Family care-givers completed a questionnaire that provided socioeconomic and behavioral information. The analysis used multivari-ate Poisson regression models adjusted for age. More than half (52.5%) of the subjects had at least one permanent or deciduous tooth affected by new caries during the longitudinal assessment (2004-2008). The incidence of caries was associated with the baseline prevalence of caries (incidence ratio = 1.92), a higher frequency of sugar intake (IR = 1.56), and having at least one sibling (IR = 1.64). Participants whose family care-givers had more education had a significantly lower incidence (IR = 0.68). The factors associated with a higher incidence of caries are similar to those in the general population. This evidence can potentially be used to develop an effective oral health promotion program for these patients. PMID- 22070361 TI - Living with facial disfigurement--strategies for individuals and care management. AB - Individuals and families affected by craniofacial disorders have expressed dissatisfaction with their experiences in the healthcare system, with day care, and in school situations. To capture their views, focus group encounters were done in a group of young individuals with these disorders and in a group of parents whose children were affected. The aim was to synthesize their attitudes and experiences into improved strategies for parents, teenagers, and professionals in the healthcare system. Their views were compiled into a document that emphasizes the responsibilities of persons with craniofacial disorders and their parents to actively seek information on diagnosis and treatment options and to participate in decisions on therapy. The conclusion was that it is not lack of specific knowledge but rather a lack of implementation of existing recommendations that makes living with facial disfigurement difficult for many individuals and their families. PMID- 22070362 TI - Improvement of mouth opening for a patient with fibrodysplasia ossificans progressiva: a case report. AB - The aim of this article is to describe the care of a patient with fibrodysplasia ossificans progressiva (FOP) and to provide dentists with a guide for how to safely care for patients with FOP. Treatment improved the patient's limited mouth opening. FOP is a rare autosomal dominant disorder characterized by congenital malformation of the fingers and toes by heterotopic ossification progressiva of the connective tissue. This ossification causes a limitation in osteoradicular mobility, mainly affecting the spine, shoulders, hips, and peripheral joints. The disease can manifest from pregnancy until adulthood, with no greater prevalence associated with race or gender. Although rare, the disease can be easily identified by its clinical features, and diagnosis can be confirmed by a radiographic examination. There is no known effective treatment for this disease. All therapeutic treatment must be conservative to avoid any condition that may cause heterotopic ossification. Guidelines to prevent new ossifications are important for patients with FOP. Dental professionals should be cautious in planning treatment, avoiding anesthesia, especially in the mandible, to prevent ankylosis of the temporo-mandibular joints. The prevention of dental caries is essential to avoid the need for more invasive treatment. PMID- 22070363 TI - Dentistry for Peruvian residents with special needs: a commentary. PMID- 22070365 TI - Carry-over effects of the membrane interface probe. AB - The membrane interface probe (MIP) is widely used to characterize the subsurface distribution of volatile organic compounds (VOCs). One problem that arises during MIP application is that disproportionately high MIP signals are obtained after passing source zones which contain mobile or residual phases. This serious problem occurs because of a carry-over effect, in particular caused by compound specific retention times in the conventional unheated transfer line, commonly used during such an investigation. The objective of this study was to perform a qualitative methodical field evaluation of the carry-over effect of a conventional MIP system with a conventional unheated transfer line. This was achieved by coupling a mobile mass spectrometer to the MIP device. Results obtained were then further compared with those achieved using a laser induced fluorescence (LIF) system. Because of this coupling, time- and depth-dependent signals for different substances became known. Field evaluation data obtained showed complex superpositions of compounds with MIP system results. As a result of this superposition, MIP signals from the saturated zone beneath the source zone (zone with free and/or residual phase) are blurred and are therefore not representative of particular depths. However, utilizing multidirectional probing alongside conventional MIP probing (forwards and backwards), it was possible to detect the upper and lower phase boundary of the source zone. These MIP results correlated excellently with the LIF results. An important conclusion that can be drawn from the field investigation is that coupling a mobile mass spectrometer to the MIP system enables advanced MIP signal interpretation to be successfully achieved. PMID- 22070368 TI - 3,5-Bis(ethynyl)pyridine and 2,6-bis(ethynyl)pyridine spanning two Fe(Cp*)(dppe) units: role of the nitrogen atom on the electronic and magnetic couplings. AB - The role of the nitrogen atom on the electronic and magnetic couplings of the mono-oxidized and bi-oxidized pyridine-containing complex models [2,6-{Cp(dpe)Fe C=C-}(2)(NC(5)H(3))](n+) and [3,5-{Cp(dpe)Fe-C=C-}(2)(NC(5)H(3))](n+) is theoretically tackled with the aid of density-functional theory (DFT) and multireference configuration interaction (MR-CI) calculations. Results are analyzed and compared to those obtained for the reference complex [1,3 {Cp*(dppe)Fe-C=C-)}(2)(C(6)H(4))](n+). The mono-oxidized species show an interesting behavior at the borderline between spin localization and delocalization and one through-bond communication path among the two involving the central ring, is favored. Investigation of the spin state of the dicationic complexes indicates ferromagnetic coupling, which can differ in magnitude from one complex to the other. Very importantly, electronic and magnetic properties of these species strongly depend not only upon the location of the nitrogen atom in the ring versus that of the organometallic end-groups but also upon the architectural arrangement of one terminus, with respect to the other and/or vis-a vis the central ring. To help validate the theoretical results, the related families of compounds [1,3-{Cp*(dppe)Fe-C=C-)}(2)(C(6)H(4))](n+), [2,6 {Cp*(dppe)Fe-C=C-}(2)(NC(5)H(3))](n+), [3,5-{Cp*(dppe)Fe-C=C-}(2)(NC(5)H(3))](n+) (n = 0-2) were experimentally synthesized and characterized. Electrochemical, spectroscopic (infrared (IR), Mossbauer), electronic (near-infrared (NIR)), and magnetic properties (electron paramagnetic resonance (EPR), superconducting quantum interference device (SQUID)) are discussed and interpreted in the light of the theoretical data. The set of data obtained allows for many strong conclusions to be drawn. A N atom in the long branch increases the ferromagnetic interaction between the two Fe(III) spin carriers (J > 500 cm(-1)), whereas, when placed in the short branch, it dramatically reduces the magnetic exchange in the di-oxidized species (J = 2.14(5) cm(-1)). In the mixed-valence compounds, when the N atom is positioned on the long branch, the intermediate excited state is higher in energy than the different ground-state conformers and the relaxation process provides exclusively the Fe(II)/Fe(III) localized system (H(ab) ? 0). Positioning the N atom on the short branch modifies the energy profile and the diabatic mediating state lies just above the reactant and product diabatic states. Consequently, the LMCT transition becomes less energetic than the MMCT transition. Here, the direct coupling does not occur (H(ab) = 0) and only the coupling through the bridge (c) and the reactant (a) and product (b) diabatic states is operating (H(ac) = H(bc) ? 0). PMID- 22070366 TI - Novel migrating mouse neural crest cell assay system utilizing P0-Cre/EGFP fluorescent time-lapse imaging. AB - BACKGROUND: Neural crest cells (NCCs) are embryonic, multipotent stem cells. Their long-range and precision-guided migration is one of their most striking characteristics. We previously reported that P0-Cre/CAG-CAT-lacZ double transgenic mice showed significant lacZ expression in tissues derived from NCCs. RESULTS: In this study, by embedding a P0-Cre/CAG-CAT-EGFP embryo at E9.5 in collagen gel inside a culture glass slide, we were able to keep the embryo developing ex vivo for more than 24 hours; this development was with enough NCC fluorescent signal intensity to enable single-cell resolution analysis, with the accompanying NCC migration potential intact and with the appropriate NCC response to the extracellular signal maintained. By implantation of beads with absorbed platelet-derived growth factor-AA (PDGF-AA), we demonstrated that PDGF-AA acts as an NCC-attractant in embryos.We also performed assays with NCCs isolated from P0 Cre/CAG-CAT-EGFP embryos on culture plates. The neuromediator 5-hydroxytryptamine (5-HT) has been known to regulate NCC migration. We newly demonstrated that dopamine, in addition to 5-HT, stimulated NCC migration in vitro. Two NCC populations, with different axial levels of origins, showed unique distribution patterns regarding migration velocity and different dose-response patterns to both 5-HT and dopamine. CONCLUSIONS: Although avian species predominated over the other species in the NCC study, our novel system should enable us to use mice to assay many different aspects of NCCs in embryos or on culture plates, such as migration, division, differentiation, and apoptosis. PMID- 22070369 TI - Effects of ethinyl estradiol and desogestrel on clinical and metabolic parameters in Indian patients with polycystic ovary syndrome. AB - AIM: The aim of this study was to examine the therapeutic effects of an ethinyl estradiol (EE) and desogestrel (DSG) combination pill in polycystic ovary syndrome (PCOS). METHODS: A total of 42 women with PCOS were treated with an EE 30 mcg and DSG 150 mcg (EE/DSG) combination pill for 12 cycles. The following parameters were studied at 0, 6, and 12months: body mass index, abdominal circumference, Ferriman-Gallwey score, presence of acne and acanthosis nigricans, serum testosterone and sex-hormone-binding globulin levels, fasting glucose and fasting insulin levels. Free androgen index and glucose:insulin ratio were calculated. RESULTS: There were significant improvements in Ferriman-Gallwey score, incidence of acne, serum testosterone and sex-hormone-binding globulin levels and free androgen index values at the 6-month follow up. But there were no further beneficial changes in the above parameters at the 12-month follow up. There were no significant changes in body mass index, abdominal circumference, incidence of acanthosis nigricans, fasting glucose and insulin levels and glucose:insulin ratio during treatment. CONCLUSION: Significant improvements in hyperandrogenic parameters were seen only in the first 6months of treatment with EE/DSG in PCOS. Further continuation with this pill did not produce any significant improvement. There were no adverse effects on insulin sensitivity. PMID- 22070370 TI - A series of 19'-hexanoyloxyfucoxanthin derivatives from the sea mussel, Mytilus galloprovincialis, grown in the Black Sea, Ukraine. AB - A series of carotenoids with 19- or 19'-hexanoyloxy moieties, 19' hexanoyloxyfucoxanthin (1), 19'-hexanoyloxyfucoxanthinol (2), 19' hexanoyloxyhalocynthiaxanthin (3), 19-hexanoyloxycrassostreaxanthin A (4), 19 hexanoyloxymytiloxanthin (5), and 19-hexanoyloxyallenicmytiloxanthin (6) were isolated from the edible part of the sea mussel, Mytilus galloprovincialis, grown in the Black Sea, Ukraine. Among them, 3, 4, and 6 were new compounds. These structures were charcterized by UV-vis, fast atom bombardment mass spectrometry, circular dichroism, and (1)H NMR spectroscopic data. They were assumed to be metabolites of 19'-hexanoyloxyfucoxanthin (1). PMID- 22070371 TI - Homogeneous detection of avidin based on switchable lanthanide luminescence. AB - We have developed switchable lanthanide luminescence-based binary probe technology for homogeneous detection of avidin, which is a tetrameric protein. Two different nonluminescent label moieties--a light-absorbing antenna ligand and a lanthanide ion carrier chelate--were conjugated to separate biotins, which is known as avidin's natural ligand. The assay was based on binding of the two differently labeled biotins on separate binding sites on the target protein and consequent self-assembly of a luminescent complex from the two label moieties. Specific luminescence signal was observed only at the presence of the target protein. The characteristics of the switchable lanthanide luminescence assay were compared to the reference assay, based on lanthanide resonance energy transfer. Both assays had a limit of detection in the low-picomolar concentration range; however, the lanthanide chelate complementation-based assay had wider dynamic range and its optimization was more straightforward. The switchable lanthanide luminescence technology could be further applied to generic protein detection, using reagents that are analogous to the proximity ligation assay principle. PMID- 22070372 TI - Active surveillance criteria for prostate cancer: can they be applied to Japanese patients? AB - Prostate-specific antigen screening has significantly increased the percentage of men who are diagnosed with low-risk prostate cancer. All men undergoing retropubic radical prostatectomy for primary treatment of prostate cancer from April 2004 to September 2010 in our hospital were examined in order to determine whether active surveillance criteria could be applied to Japanese men. From pathological data of prostate biopsies, whether these men met five published criteria for active surveillance (Johns Hopkins Medical Institution, Prostate Cancer Research International: Active Surveillance Study, University of California, San Francisco, Toronto and Kakehi criteria) was evaluated. Men who met any of the criteria had a statistically significant lower extracapsular extension rate and organ-confinement rate. From the view of the possibility of Gleason upgrading and organ-confinement rate, the Johns Hopkins Medical Institution and Prostate Cancer Research International: Active Surveillance Study criteria showed to be appropriate for Japanese patients. However, the present study had limitations of selection bias and a limited number of cases. PMID- 22070374 TI - Ionic conductivity through thermoresponsive polymer gel: ordering matters. AB - Thermoreversible polymer gel has been prepared using PEO-PPO-PEO block copolymer (Pluronic F77) which self-assembles into different microcrystalline phases like cubic, 2D-hexagonal, and lamellar. Addition of electrolyte (LiI/I(2)) converts the gel into a polymer gel electrolyte (PGE) which exhibits microphase-dependent ionic conductivity. The crystalline phases have been identified by SAXS as a function of the polymer concentration. It is found that the optimum value for the ionic conductivity (~1 * 10(-3) S x cm(-1)) is achieved in the Im3m phase due to faster diffusion of ions through the 3D-interconnected micellar nanochannels. This fact is further supported by FTIR study, ionic transference number, and diffusion coefficient measurements. PMID- 22070373 TI - Site-specific platinum(II) cross-linking in a ribozyme active site. AB - The function of RNA depends on its ability to adopt complex and dynamic structures, and the incorporation of site-specific cross-linking probes is a powerful method for providing distance constraints that are valuable in RNA structural biology. Here we describe a new RNA-RNA cross-linking strategy based on Pt(II) targeting of specific phosphorothioate substitutions. In this strategy cis-diammine Pt(II) complexes are kinetically recruited and anchored to a phosphorothioate substitution embedded within a structured RNA. Substitution of the remaining exchangeable Pt(II) ligand with a nucleophile supplied by a nearby RNA nucleobase results in metal-mediated cross-links that are stable during isolation. This type of cross-linking strategy was explored within the catalytic core of the Hammerhead ribozyme (HHRz). When a phosphorothioate substitution is installed at the scissile bond normally cleaved by the HHRz, Pt(II) cross-linking takes place to nucleotides G8 and G10 in the ribozyme active site. Both of these positions are predicted to be within ~8 A of a phosphorothioate-bound Pt(II) metal center. Cross-linking depends on Mg(2+) ion concentration, reaching yields as high as 30%, with rates that indicate cation competition within the RNA three helix junction. Cross-linking efficiency depends on accurate formation of the HHRz tertiary structure, and cross-links are not observed for RNA helices. Combined, these results show promise for using kinetically inert Pt(II) complexes as new site-specific cross-linking tools for exploring RNA structure and dynamics. PMID- 22070375 TI - Maintaining faith in agency under immutable constraints: cognitive consequences of believing in negotiable fate. AB - Negotiable fate refers to the idea that one can negotiate with fate for control, and that people can exercise personal agency within the limits that fate has determined. Research on negotiable fate has found greater prevalence of related beliefs in Southeast Asia, East Asia, and Eastern Europe than in Western Europe and English-speaking countries. The present research extends previous findings by exploring the cognitive consequences of the belief in negotiable fate. It was hypothesized that this belief enables individuals to maintain faith in the potency of their personal actions and to remain optimistic in their goal pursuits despite the immutable constraints. The belief in negotiable fate was predicted to (a) facilitate sense-making of surprising outcomes; (b) increase persistence in goal pursuits despite early unfavorable outcomes; and (c) increase risky choices when individuals have confidence in their luck. Using multiple methods (e.g., crosscultural comparisons, culture priming, experimental induction of fate beliefs), we found supporting evidence for our hypotheses in three studies. Furthermore, as expected, the cognitive effects of negotiable fate are observed only in cultural contexts where the fate belief is relatively prevalent. Implications of these findings are discussed in relation to the intersubjective approach to understanding the influence of culture on cognitive processes (e.g., Chiu, Gelfand, Yamagishi, Shteynberg, & Wan, 2010), the sociocultural foundations that foster the development of a belief in negotiable fate, and an alternative perspective for understanding the nature of agency in contexts where constraints are severe. Future research avenues are also discussed. PMID- 22070376 TI - Exploiting the acylating nature of the imide-Ugi intermediate: a straightforward synthesis of tetrahydro-1,4-benzodiazepin-2-ones. AB - We describe a simple and novel protocol for the synthesis of tetrahydro-1,4 benzodiazepin-2-ones with three points of diversity, exploiting the acylating properties of the recently rediscovered Ugi-imide. The final compounds can be easily prepared in three synthetic steps using a multicomponent reaction, a Staudinger reduction, and an acylative protocol, with good to excellent yields for each synthetic step. PMID- 22070377 TI - Borrelia burgdorferi infections with special reference to horses. A review. AB - Summary This review discusses the literature on B. burgdorferi infections in view of the rising incidence of this infection in general and the increasing concerns of horse owners and equine practitioners. Lyme disease, the clinical expression of Borrelia infections in man is an important health problem. The geographic distribution of B. burgdorferi infections in equidae should resemble that of human cases because the vector tick involved, Ixodes ricinus, feeds on both species and, indeed, the infection has been established many times in horses. However, a definite diagnosis of the disease "Lyme borreliosis" in human beings as well as in horses and other animals is often difficult to accomplish. Although a broad spectrum of clinical signs has been attributed to B. burgdorferi infections in horses, indisputable cases of equine Lyme borreliosis are extremely rare so far, if they exist at all. PMID- 22070378 TI - Use of plasma ionized calcium levels and Ca(2+) substitution response patterns as prognostic parameters for ileus and survival in colic horses. AB - Summary Objective: Hypocalcaemia is a common finding in horses with enterocolitis and severe gastrointestinal disorders. The aims of this study were to investigate in colic horses (!))the parameters related to hypocalcaemia, (2))the influence of hypocalcaemia on outcome and (3))the possible beneficial effect of Ca(2+ )substitution. Design: Randomized controlled trial. Setting: Intensive care unit. Patients: One hundred forty-four horses that were admitted with an acute abdomen during a 1.5 year period were enrolled and daily evaluated for clinical criteria and whole blood ionized Ca levels. Colic horses with hypocalcaemia were randomly assigned to receive Ca(2+). Interventions: Analysis of heparinised whole blood samples. Horses that were assigned to be treated received 400 mEq Ca(2+) diluted in 10L of Ringer's lactate solution every 24 h until low reference range limits were obtained or until death. Measurements and main results: 88% of all colic patients showed blood ionized Ca levels below the reference range at the time of admission. Multivariable analysis revealed that the presence of reflux signs of endotoxaemia increased Packed Cell Volume (PCV) alkalinization of pH and the interaction PCV/pH all predispose colic horses to low ionized Ca(2+) levels at the time of admission. The Odds for developing ileus during hospitalization are +/- 11.94 times larger for horses in the "very low" calcaemia interval in comparison with normocalcaemic horses. The Odds for fatal outcome are respectively +/- 9.82 and 8.33 times larger for horses in the "very low" and "low" calcaemia interval. Ca(2+) substitution increased the probability of survival provided that Ca(2+) levels could be normalized. The lack of an upward calcaemia response despite repetitive Ca(2+) substitutions can be guarded as a poor ominous sign. Conclusions: Hypocalcaemia in colic horses is of prognostic relevance both with regard to survival as to the probability of development of ileus during hospitalization. This study shows the importance of routine measurement of ionized calcium levels in colic horses. Moreover correction of hypocalcaemia seems to improve clinical outcome. PMID- 22070379 TI - Cystic endometrial hyperplasia-pyometra complex in cats. A review. AB - Summary Presentation of complex cystic endometrial hyperplasia-pyometra is not very common in cats. As in bitches, hormonal influences result in environmental and histological changes in the uterus leading to predisposition to bacterial growth. Its influence on the organism provokes certain clinical signs. Diagnosis and treatment must be fast and aggressive. Depending on the clinical status and queen purpose, it can be both surgical or medical. Both of them offer a high rate of success if the detailed protocols are followed. PMID- 22070380 TI - Analysis of the 96 most often cited articles published in veterinary journals in 2002 and 2003. AB - Summary The study concerned 123 Journals of the category "Veterinary Sciences" as defined in the Journal Citation Reports ((c), Institute for Scientific Information (ISI), Philadelphia, USA). Using Web of Knowledge ((c), ISI, USA), update December 3, 2005, articles published in 2002 and 2003 and cited 20 times or more were selected. The total number of selected articles was 96. They were published in 34 out of the 123 journals. Based on the country of the first author, the articles originated form 24 countries. Forty-nine of the 96 articles (51%) were written in only two countries being England (15) and the USA (34). The articles could be classified in six categories being immunology (21), microbiology and directly related subjects (48), prions and prion-induced diseases (5), reproduction (23), toxicology (3), and miscellanea (11). The category "microbiology" (48) was divided into six subcategories: general (1), bacteriology (17), mycology (3), parasitology (5), protozoology (6), and virology (5). Some articles were classified in more than one (sub)category. PMID- 22070382 TI - The experience of young people with depression: a qualitative study. AB - People who develop depression experience a maelstrom of emotions as they struggle to understand what is happening to them. While the experience has been comparatively well documented in older adults, much less is known about the depression experience and responses of young people. In this study, we aimed to explore the experience of young people diagnosed with depression. Twenty-six young people were recruited from a youth mental health service. A qualitative interpretative design was used, incorporating semi-structured, audio-recorded interviews. Results provided four overlapping themes, reflecting the young people's difficulties in coming to terms with, and responding in self-protective, harmful and at times life-threatening ways to their depression: (1) struggling to make sense of their situation; (2) spiralling down; (3) withdrawing; and (4) contemplating self-harm or suicide. Study conclusions are that young people faced considerable difficulties coming to terms with, and responding to, depression. Improving young people's understanding of depression and its treatment, reducing community stigma and providing accessible and youth-focused services remain important targets for intervention. It is also important to improve mental health literacy in the community to increase awareness of depression and how mental health professionals, including nurses, respond effectively to the young person. PMID- 22070383 TI - Investigating the role of zinc in a rat model of epilepsy. AB - AIMS: The aim of the present study was to investigate the role of zinc (Zn) in pilocarpine-induced seizures and its interrelation with an antiepileptic drug, namely, valproic acid. METHODOLOGY: The study was carried out on 110 male Wistar albino rats that were divided into the following groups: Group I, control rats that received intraperitoneal (i.p.) saline vehicle; Groups II-V received Zn in a medium dose, Zn in a high dose, valproic acid in a therapeutic dose, as well as a combination of valproic acid with medium dose Zn, respectively, for 3 weeks before saline injection, Group VI received i.p. pilocarpine to induce seizures; Groups VII-XI received Zn in a medium dose, Zn in a high dose, valproic acid in a therapeutic dose, a combination of therapeutic dose of valproic acid with medium dose Zn, as well as a combination of subeffective dose of valproic acid with medium dose of Zn, respectively, for 3 weeks before pilocarpine injection. The seizure's latency and severity for each rat was recorded. Blood and brain hippocampal samples were collected for determination of serum neuron specific enolase (NSE), hippocampal Zn, interleukin-1 beta concentrations as well as hippocampal superoxide dismutase and caspase-3 activities. RESULTS: The results of the current study demonstrated that pretreatment with high dose of Zn exacerbated pilocarpine-induced seizures. Whereas, a medium dose of Zn and valproic acid either alone or in combination reduced the severity of pilocarpine induced limbic seizures and increased the latency to attain the forelimb clonus. Also both drugs, either alone or in combination, ameliorated all studied biochemical parameters with the exception of hippocampal Zn concentration, which was only significantly increased by pretreatment with Zn, either alone or in combination with valproic acid. CONCLUSIONS: The present study highlights the antiepileptic role that could be played by Zn, when given in appropriate doses. PMID- 22070384 TI - Reversible translocation of ASK1 to a Triton-X100 insoluble cytoplasmic compartment during cardiac myocyte cell stress. AB - ASK1 is a cellular stress-responsive MAPKKK which activates the JNK and p38 MAPK pathways that play a key role in the response of cardiac myocytes to redox stress following ischemia/reperfusion. ASK1 becomes incorporated into high-molecular weight complexes upon activation but this has not been investigated in cardiac myocytes. Here we examine the distribution of ASK1 in neonatal rat cardiomyocytes undergoing simulated ischemia and reperfusion. Simulated ischemia or redox stress in neonatal cardiac myocytes causes the translocation of ASK1 to distinct punctate cytoplasmic structures that are insoluble in Triton X-100. The translocation event is not dependent on ASK1 kinase activity, occurs subsequent to activation and is reversible upon removal of the cell stress. The structures to which ASK1 translocates in cardiac myocytes do not appear to correspond to the previously described ASK1 signalosome reported in other cell types. PMID- 22070385 TI - Chemotactic effect of odorants and tastants on the ciliate Tetrahymena pyriformis. AB - Naturally occurring aroma compounds are able to elicit physiological and migratory responses such as chemotaxis even at nano to femtomolar concentrations in organisms at different levels of phylogeny. Despite the amazing chemical variety of these substances the apparatus by which they can be detected i.e. the chemosensory receptors and the signaling pathways seem to be rather uniform and evolutionary well-conserved. The intracellular signaling process is supposed to be mediated by either cAMP or inositol 1,4,5-trisphosphate. The present work aimed to investigate the chemotactic behavior of 11 odorants that occur naturally in foods and are also used by the industry as additives, on the eukaryotic ciliate Tetrahymena pyriformis. Intracellular signaling pathways that might be activated by these compounds were also investigated. Activation of the phospholipase C (PLC) was measured by FACS and the stimulation of inositol-1,4,5 trisphosphate 3-kinases (IP3K) was measured using two specific inhibitors, wortmannin and LY294002. The strongest chemoattractant character was observed for isoamyl acetate (10(-6) M), propyl isobutyrate (10(-8) M), isobutyl propionate (10(-6) M). The strongest repellent action was exerted by benzyl acetate (10(-8) M), furfuryl thioacetate (10(-12) M). Our results suggest that Tetrahymena responds in a very sensitive way to slight changes in the molecular structure. According to our study, tracer amounts of solvents do not contribute significantly to the chemotactic profile of the respective odorants. No significant activation of PLC or PI3K could be observed following stimulation with attractant odorants which implies that some other pathways may be involved, hence further investigation is needed. PMID- 22070386 TI - Cigarette smoke-induced pulmonary inflammation is attenuated in CD69-deficient mice. AB - Cluster of differentiation 69 (CD69) has been identified as a lymphocyte early activation marker, and recent studies have indicated that CD69 mediates intracellular signals and plays an important role in various inflammatory diseases. Cigarette smoke (CS) is a strong proinflammatory stimulus that induces the release of proinflammatory mediators by recruiting macrophages and neutrophils into the lung tissue, and is one of the main risk factors for a number of chronic diseases. However, the potential role of CD69 in CS-induced pulmonary inflammation has not been determined. To address to this question, CD69 deficient (KO) and wild-type (WT) mice were subjected to CS-induced acute pulmonary inflammation. After the exposure with CS, the expression of CD69 in the lung of WT mice was significantly induced, it was predominantly observed in macrophages. In conjunction with this phenomenon, neutrophil and macrophage cell counts, and expression of several cytokines were significantly higher in the bronchoalveolar lavage fluid (BALF) of CS-exposed WT mice compared with air exposed WT mice. Likewise, the CS-induced accumulation of inflammatory cells and cytokines expression were significantly lower in CD69-KO mice than in WT mice. These results suggest that CD69 on macrophages is involved in CS-induced acute pulmonary inflammation. PMID- 22070387 TI - Hydrogen bonding in the electronic excited state. AB - Because of its fundamental importance in many branches of science, hydrogen bonding is a subject of intense contemporary research interest. The physical and chemical properties of hydrogen bonds in the ground state have been widely studied both experimentally and theoretically by chemists, physicists, and biologists. However, hydrogen bonding in the electronic excited state, which plays an important role in many photophysical processes and photochemical reactions, has scarcely been investigated. Upon electronic excitation of hydrogen-bonded systems by light, the hydrogen donor and acceptor molecules must reorganize in the electronic excited state because of the significant charge distribution difference between the different electronic states. The electronic excited-state hydrogen-bonding dynamics, which are predominantly determined by the vibrational motions of the hydrogen donor and acceptor groups, generally occur on ultrafast time scales of hundreds of femtoseconds. As a result, state-of the-art femtosecond time-resolved vibrational spectroscopy is used to directly monitor the ultrafast dynamical behavior of hydrogen bonds in the electronic excited state. It is important to note that the excited-state hydrogen-bonding dynamics are coupled to the electronic excitation. Fortunately, the combination of femtosecond time-resolved spectroscopy and accurate quantum chemistry calculations of excited states resolves this issue in laser experiments. Through a comparison of the hydrogen-bonded complex to the separated hydrogen donor or acceptor in ground and electronic excited states, the excited-state hydrogen bonding structure and dynamics have been obtained. Moreover, we have also demonstrated the importance of hydrogen bonding in many photophysical processes and photochemical reactions. In this Account, we review our recent advances in electronic excited-state hydrogen-bonding dynamics and the significant role of electronic excited-state hydrogen bonding on internal conversion (IC), electronic spectral shifts (ESS), photoinduced electron transfer (PET), fluorescence quenching (FQ), intramolecular charge transfer (ICT), and metal-to-ligand charge transfer (MLCT). The combination of various spectroscopic experiments with theoretical calculations has led to tremendous progress in excited-state hydrogen bonding research. We first demonstrated that the intermolecular hydrogen bond in the electronic excited state is greatly strengthened for coumarin chromophores and weakened for thiocarbonyl chromophores. We have also clarified that the intermolecular hydrogen-bond strengthening and weakening correspond to red-shifts and blue-shifts, respectively, in the electronic spectra. Moreover, radiationless deactivations (via IC, PET, ICT, MLCT, and so on) can be dramatically influenced through the regulation of electronic states by hydrogen-bonding interactions. Consequently, the fluorescence of chromophores in hydrogen-bonded surroundings is quenched or enhanced by hydrogen bonds. Our research expands our understanding of the nature of hydrogen bonding by delineating the interaction between hydrogen bonds and photons, thereby providing a basis for excited-state hydrogen bonding studies in photophysics, photochemistry, and photobiology. PMID- 22070388 TI - Biosynthesis of the biomarker okenone: chi-ring formation. AB - Purple sulfur bacteria (PSB) mainly occur in anoxic aquatic and benthic environments, where they play important roles in cycling carbon and sulfur. Many PSB characteristically produce the unique keto-carotenoid, okenone, which is important not only for its light absorption and photoprotection properties but also because of its diagenesis product, okenane, which is a biomarker for ancient sediments derived from anoxic environments. The specific methylation pattern of the chi-ring of okenane is unlikely to be formed by diagenetic processes and should therefore reflect an enzymatic activity from okenone biosynthesis. This study describes two enzymes that produce the chi-ring of okenone, the only structural element of okenone preserved in okenane. Genes encoding enzymes of carotenogenesis were identified in the draft genome sequence of an okenone producing PSB, Thiodictyon sp. strain CAD16. Two divergently transcribed genes encoded a CrtY-type lycopene cyclase and a CrtU/CruE-type gamma-carotene desaturase/methyltransferase. Expression of crtY in Escherichia coli showed that this gene encoded a lycopene cyclase that produced gamma-carotene as the only product. Although the sequence of the gamma-carotene desaturase/methyltransferase was more similar to CrtU sequences of green sulfur bacteria than to CruE sequences of cyanobacteria, expression of the crtU gene in Chlorobaculum tepidum showed that the enzyme produced carotenoids with chi-rings rather than phi-rings. Phylogenetic analysis of the carotene desaturase/methyltransferases revealed that enzymes capable of converting beta-rings to chi-rings have independently evolved at least two times. These results indicate that it probably will not be possible to deduce the activity of carotene desaturase/methyltransferases solely from sequence data. PMID- 22070389 TI - Willingness to pay as patient preference to bariatric surgery. AB - BACKGROUND: An obesity epidemic is spreading worldwide. In addition to comorbidities, social and emotional problems contribute to reduce the quality of life (QoL) of obese people. Considering the heterogeneity of outcomes from clinical and surgical approaches, it is recommended that severely obese patients participate in their treatment decisions. This study evaluated preferences of severely obese patients for obesity surgical treatment using the willingness to pay (WTP) and to assess the impact of the presence of some clinical disorders, socioeconomic conditions and QoL on their decisions. METHODS: The selected patients were invited to answer the WTP questionnaire using two formats of contingent valuation questions: dichotomous choice (yes/no) and a bidding game. The answers were correlated with clinical features, QoL assessed by the SF-36 and the Moorehead-Ardelt Quality of Life Questionnaire II, Brazilian socioeconomic classification, and family and personal incomes. RESULTS: The group of patients who accepted the first bid was older and had higher frequency of sleep apnoea when compared to those who rejected the offer. A significant correlation between the bidding game value and family income was found (r = 0.28; P < 0.02). In the logistic regression model, socioeconomic classification and sleep apnoea were shown to be independently associated with acceptance the bid. CONCLUSIONS: Sleep apnoea was the comorbidity that most influenced the acceptance in dichotomous choice for bariatric surgery, probably due to the deleterious effects on daily activities induced by sleep disturbances. Our findings also suggest that the frequency of surgical procedures is below the preference of the obese population in Brazil. PMID- 22070390 TI - Acute mental health nurses: comprehensive practitioners or specialist therapists? AB - This paper examines the aids and barriers to implementing the psychosocial interventions (PSI) which trainees learned on two teaching modules. The main purpose of the modules is to teach trainees PSI to help them be more effective in their care of patients with severe mental illness. The trainees were qualified nurses working in acute mental health wards in various London hospitals. PSI has been found to be helpful for patients with psychotic symptoms in community contexts. In this study, the implementation of PSI specific to acute inpatient mental health settings is explored. This was achieved by conducting semi structured audiotaped interviews with all 20 trainees from a single cohort. The data were analysed by categories and themes to elicit not only the problems but also helpful strategies which can be used when working with PSI in acute inpatient mental health settings. The paper concludes by offering recommendations for future good practice for this area of mental health service. PMID- 22070391 TI - Serum albumin binding of structurally diverse neutral organic compounds: data and models. AB - Binding to serum albumin has a strong influence on freely dissolved, unbound concentrations of chemicals in vivo and in vitro. For neutral organic solutes, previous studies have suggested a log-log correlation between the albumin-water partition coefficient and the octanol-water partition coefficient (K(ow)) and postulated highly nonspecific binding that is mechanistically analogous to dissolution into solvents. These relationships and concepts were further explored in this study. Bovine serum albumin (BSA)-water partition coefficients (K(BSA/w)) were measured for 83 structurally diverse neutral organic chemicals in consistent experimental conditions. The correlation between log K(BSA/w) and log K(ow) was moderate, with R(2) = 0.76 and SD = 0.43. The log K(BSA/w) of low-polarity compounds including a series of chlorobenzenes and polycyclic aromatic hydrocarbons increased with log K(ow) linearly up to log K(ow) = 4-5, but then the linear relationship apparently broke off, and the increase became gradual. The fitting of polyparameter linear free energy relationship models with five solute descriptors was just comparable to that of the log K(ow) model (R(2) = 0.78-0.79, SD = 0.41-0.42); the relatively high SD obtained suggests that solvent dissolution models are not capable of modeling albumin binding accurately. A size limitation of the binding site(s) of albumin is suggested as a possible reason for the high SD. An equilibrium distribution model indicates that serum albumin generally has high contributions to the binding in the serum of polar compounds and relatively small low-polarity compounds, whereas albumin binding for large low-polarity compounds is outcompeted by the strong partitioning into lipids due to low relative affinity of albumin for these compounds. PMID- 22070392 TI - Oral rosmarinic acid-enhanced Mentha spicata modulates synovial fluid biomarkers of inflammation in horses challenged with intra-articular LPS. AB - A biological extract of high-rosmarinic acid mint (HRAM) has previously demonstrated inhibitory effects on lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)), nitric oxide (NO) and glycosaminoglycan (GAG) release in vitro. This study was undertaken to determine whether HRAM added to feed produces similar effects in horses challenged with intra-articular LPS. Eight horses received HRAM (0 or 28.1 +/- 1.3 g/day; n = 4 per group) in their feed for 24 days in a blinded manner. On day 21, all horses received an intra-articular injection of LPS (0.3 ng) into their left or right intercarpal joint. Synovial fluid (SF) samples were taken on postinjection day (PID)-21 (i.e. prior to commencement of supplementation), PID0, PID0.25, PID0.5, PID1 and PID3 and analysed for PGE(2), GAG, NO, protein and total nucleated cells counts. Blood biochemistry and haematology screens were conducted at PID-21, PID0, PID1 and PID3. There was a significant reduction in LPS-induced PGE(2) and GAG in SF in horses supplemented with HRAM compared with controls and a tendency to increase complement recognition protein accumulation in synovial fluid of HRAM horses. Plasma from HRAM horses had reduced total white blood cells, segmented neutrophils (compared with baseline concentrations) and lymphocytes (compared with controls), and increased SF nucleated cell count (compared with baseline concentrations and controls). It is concluded that HRAM offered as part of the feed alter biomarkers of inflammation in SF of LPS-challenged horses. Larger studies that seek to clarify effects of HRAM on synovial fluid cell counts and possible role of HRAM-induced interference with complement signalling are warranted. PMID- 22070393 TI - Implementing a structured psychosocial interventions group programme for people with bipolar disorder. AB - It has been reported that, at any time, over half of the people with bipolar disorder are receiving no active treatment. Despite the availability of effective medications and psychotherapies, research concludes that the care of bipolar disorder in everyday practice is often deficient. Evidence base reports the effectiveness of psychosocial interventions using many of the same ideas as the recovery approach; both attempt to place clients at the heart of service delivery. This paper reports on the development and implementation of three pilot group programmes for service users with bipolar disorder, in a community clinical setting in South East England. The group programme design and development was based upon the evidence-based psychosocial interventions advocated in national clinical guidelines and research literature. The programme incorporated the key effective psychosocial interventions and self-management mechanisms within its 12 sessions spanning over 3 months, followed by three booster sessions in 6 months' time. Twenty-three service users have to date completed the programme. Participant feedback will be discussed and reported to inform further development and research implications of such innovative evidence-based interventions for service users with bipolar disorder. PMID- 22070394 TI - Comparison of homoeologous chromosome pairing between hybrids of wheat genotypes Chinese Spring ph1b and Kaixian-luohanmai with rye. AB - The ph-like genes in the Chinese common wheat landrace Kaixian-luohanmai (KL) induce homoeologous pairing in hybrids with alien species. In the present study, meiotic phenotypic differences on homoeologous chromosome pairing at metaphase I between hybrids of wheat genotypes Chinese Spring ph1b (CSph1b) and KL with rye were studied by genomic in situ hybridization (GISH). The frequency of wheat wheat associations was higher in CSph1b*rye than in KL*rye. However, frequencies of wheat-rye and rye-rye associations were higher in KL*rye than in CSph1b*rye. These differences may be the result of different mechanisms of control between the ph-like gene(s) controlling homoeologous chromosome pairing in KL and CSph1b. Wheat-wheat associations were much more frequent than wheat-rye pairing in both hybriods. This may be caused by lower overall affinity, or homoeology, between wheat and rye chromosomes than between wheat chromosomes. PMID- 22070395 TI - Clinical aspect of reproductive immunology. PMID- 22070396 TI - Obesity and psychotropics. AB - Weight gain is on the rise in the United States as is the diagnosis and treatment of mental disorders. These two phenomena are distinctly separate but tend to overlap in that most psychotropic agents approved for use in the United States are associated with the potential to induce weight gain. Metabolic disorders such as diabetes, hypercholesterolemia, and hypertension are also on the rise and often associated with weight gain and clearly associated with certain psychotropic medications. This article serves to provide a succinct review regarding the epidemiology, etiology, and treatment options for psychotropic induced obesity. PMID- 22070397 TI - Akt and RhoA inhibition promotes anoikis of aggregated B16F10 melanoma cells. AB - In the highly metastatic B16F10 melanoma cell line, activation of the signalling molecules that promote cell proliferation and survival on conventional adhesive culture dishes may also be responsible for the growth and resistance to anoikis of aggregates on a non-adhesive substratum. We have examined the influence of bacterial ADP-ribosyltransferases C3-like exoenzymes, which selectively modify RhoA, B and C proteins and inhibit signal pathways controlled by them. RNA interference [siRNA (small interfering RNA) Akt (also known as protein kinase B)] and a PI3K (phosphoinositide 3-kinase) inhibitor were used to analyse the changes caused by inhibiting the PI3K/Akt pathway. Inhibiting the activation of RhoA, B, C and Akt expression resulted in a decrease of the number of cells cultured in aggregates, and caspase 3 activation. RhoA activation and RhoB and RhoC expression were controlled by Akt, but not RhoA expression. Inhibiting Akt and RhoA reduced the expression of alpha5 integrin, and inactivated FAK (focal adhesion kinase) in B16F10 cells cultured as aggregates. Thus, inhibiting Rho subfamily proteins and Akt expression inactivates the FAK pathway and induces anoikis in anoikis-resistant cells. The activation of RhoA in melanoma cells can depend on PI3K/Akt activation, suggesting that PI3K/Akt is a suitable target for new therapeutic approaches. PMID- 22070398 TI - Parents' discursive resources: analysis of discourses in Swedish, Danish and Norwegian health care guidelines for children with diabetes type 1. AB - The incidence of diabetes type 1 in children, the most common metabolic disorder in childhood, increases worldwide, with highest incidence in Scandinavia. Having diabetes means demands in everyday life, and the outcome of the child's treatment highly depends on parents' engagement and involvement. The aim of this study was to explore and describe discourses in health care guidelines for children with diabetes type 1, in Sweden, Norway and Denmark during 2007-2010, with a focus on how parents were positioned. As method a Foucauldian approach to discourse analysis was applied, and a six-stage model was used to perform the analysis. The findings shows a Medical, a Pedagogic and a Public Health discourse embedded in the hegemonic Expert discourse. The Expert discourse positioned parents as dependent on expert knowledge, as recipients of education, as valuable and responsible for their child's health through practicing medical skills. This positioning may place parents on a continuum from being deprived of their own initiatives to being invited to take an active part and could result in feelings of guilt and uncertainty, but also of security and significance. From this study we conclude that guidelines rooted in the Expert discourse may reduce opportunities for parents' voices to be heard and may overlook their knowledge. By broadening the selection of authors of the guidelines to include patients and all professionals in the team, new discourses could emerge and the parents' voice might be more prominent. PMID- 22070399 TI - Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma and precursor lesions. PMID- 22070400 TI - Patient diaries as a clinical endpoint in Parkinson's disease clinical trials. AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder with an estimated 4 million patients worldwide. L-dopa is standard, and often initial, therapy for patients with this condition; however, with continued dopaminergic treatment and as the disease progresses, the majority of patients experience complications such as "wearing-off" symptoms, dyskinesias, and other motor complications. These complications may become disabling and profoundly affect quality of life. Treatment modification and combination therapies with L dopa, dopamine agonists, monoamine oxidase type B inhibitors, and catechol-O methyltransferase inhibitors are commonly used to manage complications. In recent years regulatory agencies, clinical researchers, and sponsors have widely accepted and utilized changes in "ON" and "OFF" time measured by Patient Hauser Diaries as endpoints for measuring efficacy of therapeutics seeking approval for symptomatic treatment of PD. Successful antiparkinsonian medications have been associated with treatment effects of more than 1 h in either reduction of "OFF" time of increase in "ON" time. Accurate "ON" and "OFF" time registration during clinical studies requires rigorous patient training. Reduced compliance, recall bias and diary fatigue are common problems seen with patient diary reported measures. Electronic diaries may help reducing some of these problems but may be associated with other challenges in large, multicenter studies. PMID- 22070401 TI - The cholesterol hypothesis: time for the obituary? AB - The cholesterol hypothesis links cholesterol intake and blood levels to cardiovascular disease. It has had enormous impact on health care and society during decades, but has little or no scientific backing that is relevant for the human species. Apparently, the hypothesis is false and should be buried. PMID- 22070402 TI - Endothelial factors after selective retrograde coronary venous bypass under different pressures. AB - BACKGROUND: Selective retrograde coronary venous bypass (SRCVB) may be a promising treatment for patients with advanced coronary artery disease (CAD). The aim of this study is to investigate the effect of SRCVB on plasma endothelial factor levels in dog myocardial ischemic model, and explore the possible mechanisms. METHODS: 24 crossbreed dogs were randomly divided into three groups: (1) control group; (2) SRCVB group with 60 mmHg perfusion pressure; (3) SRCVB group with 90 mmHg perfusion pressure. The posterior descending coronary artery (PDA) was ligated in all groups, and SRCVB was performed in the last two groups. The levels of plasma nitric oxide (NO) and endothelin (ET) at different time points were determined in each group. In SRCVB groups, ink and imaging agent were injected to the heart through SVG graft for assessment of vein perfusion. RESULTS: At the acute period, there were significant increase in the plasma levels of NO and decrease in ET in SRCVB 90 mmHg group compared with the control (P < 0. 01), and a further improvement were found in SRCVB 60 mmHg group (P < 0. 01). The ink or imaging agent was found in the myocardial tissue and flowed back to right atrium through contralateral coronary vein. CONCLUSIONS: SRCVB with low level of perfusion pressure could provide effective perfusion for ischemic myocardium and alleviate the myocardial endothelial cell injury. It may be a new therapeutic strategy for severe CAD. PMID- 22070404 TI - Approximate solutions for radial travel time and capture zone in unconfined aquifers. AB - Radial time-of-travel (TOT) capture zones have been evaluated for unconfined aquifers with and without recharge. The solutions of travel time for unconfined aquifers are rather complex and have been replaced with much simpler approximate solutions without significant loss of accuracy in most practical cases. The current "volumetric method" for calculating the radius of a TOT capture zone assumes no recharge and a constant aquifer thickness. It was found that for unconfined aquifers without recharge, the volumetric method leads to a smaller and less protective wellhead protection zone when ignoring drawdowns. However, if the saturated thickness near the well is used in the volumetric method a larger more protective TOT capture zone is obtained. The same is true when the volumetric method is used in the presence of recharge. However, for that case it leads to unreasonableness over the prediction of a TOT capture zone of 5 years or more. PMID- 22070403 TI - Unusual multi-step sequential Au(III)/Au(II) processes of gold(III) quinoxalinoporphyrins in acidic non-aqueous media. AB - The electrochemistry of gold(III) mono- and bis-quinoxalinoporphyrins was examined in CH(2)Cl(2) or PhCN containing 0.1 M tetra-n-butylammonium perchlorate (TBAP) before and after the addition of trifluoroacetic acid to solution. The investigated porphyrins are represented as Au(PQ)PF(6) and Au(QPQ)PF(6), where P is the dianion of the 5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)porphyrin and Q is a quinoxaline group fused to a beta,beta'-pyrrolic position of the porphyrin macrocycle; in Au(QPQ)PF(6) there is a linear arrangement where the quinoxalines are fused to pyrrolic positions that are opposite each other. The porphyrin without the fused quinoxaline groups, Au(P)PF(6), was also investigated under the same solution conditions. In the absence of acid, all three gold(III) porphyrins undergo a single reversible Au(III)/Au(II) process leading to the formation of a Au(II) porphyrin which can be further reduced at more negative potentials to give stepwise the Au(II) porphyrin pi-anion radical and dianion, respectively. However, in the presence of acid, the initial Au(III)/Au(II) processes of Au(PQ)PF(6) and Au(QPQ)PF(6) are followed by an internal electron transfer and protonation to regenerate new Au(III) porphyrins assigned as Au(III)(PQH)(+) and Au(III)(QPQH)(+). Both protonated gold(III) quinoxalinoporphyrins then undergo a second Au(III)/Au(II) process at more negative potentials. The electrogenerated monoprotonated monoquinoxalinoporphyrin, Au(II)(PQH), is then further reduced to its pi-anion radical and dianion forms, but this is not the case for the monoprotonated bis-quinoxalinoporphyrin, Au(II)(QPQH), which accepts a second proton and is rapidly converted to Au(III)(HQPQH)(+) before undergoing a third Au(III)/Au(II) process to produce Au(II)(HQPQH) as a final product. Thus, Au(P)PF(6) undergoes one metal-centered reduction while Au(PQ)PF(6) and Au(QPQ)PF(6) exhibit two and three Au(III)/Au(II) processes, respectively. These unusual multistep sequential Au(III)/Au(II) processes were monitored by thin layer spectroelectrochemistry and a reduction/oxidation mechanism for Au(PQ)PF(6) and Au(QPQ)PF(6) in acidic media is proposed. PMID- 22070406 TI - In situ oxidation study of Pt(110) and its interaction with CO. AB - Many interesting structures have been observed for O(2)-exposed Pt(110). These structures, along with their stability and reactivity toward CO, provide insights into catalytic processes on open Pt surfaces, which have similarities to Pt nanoparticle catalysts. In this study, we present results from ambient-pressure X ray photoelectron spectroscopy, high-pressure scanning tunneling microscopy, and density functional theory calculations. At low oxygen pressure, only chemisorbed oxygen is observed on the Pt(110) surface. At higher pressure (0.5 Torr of O(2)), nanometer-sized islands of multilayered alpha-PtO(2)-like surface oxide form along with chemisorbed oxygen. Both chemisorbed oxygen and the surface oxide are removed in the presence of CO, and the rate of disappearance of the surface oxide is close to that of the chemisorbed oxygen at 270 K. The spectroscopic features of the surface oxide are similar to the oxide observed on Pt nanoparticles of a similar size, which provides us an extra incentive to revisit some single-crystal model catalyst surfaces under elevated pressure using in situ tools. PMID- 22070405 TI - Mean Platelet Volume and Platelet Distribution Width in non-diabetic subjects with obstructive sleep apnoea syndrome: new indices of severity? AB - To evaluate Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in non-diabetic subjects, according to obstructive sleep apnoea syndrome (OSAS) severity and the associations of these indices with anthropometric characteristics and parameters of breathing function during sleep. MATERIALS AND METHODS: We included 610 non-diabetic subjects with suspected OSAS, evaluated by polysomnography. According to their apnoea-hypopnoea index (AHI), patients were divided into Group A (n=148) with AHI<5/h; Group B (n=121) with AHI: 5-14.9/h; Group C (n=85) with AHI: 15-29.9/h and Group D (n=256) with AHI >= 30/h. MPV and PDW were measured using an automated blood cell counter. RESULTS: MPV was significantly higher in group D (mean value 12.1 +/- 1.3 fl) than in groups A (9.8 +/- 1.1 fl), B (9.8 +/- 1.6 fl), and C (11.5 +/- 1.3 fl) (p<0.001). The same pattern was observed in PDW values (15.9 +/- 2.2 fl for group D and 13.2 +/- 2.2 fl for group A, 14.1 +/- 2.8 fl for group B, and 15 +/- 2.2 fl for group C, p<0.001). Significant correlations were seen between MPV and AHI (p<0.001), average pulse oxygen saturation (SpO(2)) (p<0.001), minimum SpO(2) (p<0.001) and percent of the total sleep time with SpO(2) lower than 90% (t<90%) (p<0.001) during sleep, Arousal Index (p<0.001) and Epworth sleepiness scale (ESS) (p=0.028). Similarly, PDW was correlated with AHI (p<0.001), average SpO(2) (p=0.001), minimum SpO(2) (p<0.001), t<90% (p=0.002), and Arousal Index (p<0.001). CONCLUSIONS: MPV and PDW are higher in non-diabetic patients with severe OSAS and are correlated with different parameters of breathing function during sleep. PMID- 22070407 TI - Coupling stimuli-responsive magnetic nanoparticles with antibody-antigen detection in immunoassays. AB - Because current homogeneous immunoassays show some limitations, particularly low sensitivity, we developed a new immunoassay to overcome these limitations. The approach was based on magnetic nanoparticles with a thermoresponsive polymer layer, a negatively charged polymer, and streptavidin-biotin-based antibody antigen detection and yielded higher sensitivity than commonly used heterogeneous immunoassays. Because no special equipment is needed, it can be applied to currently available absorbance-based systems for high-throughput assays. PMID- 22070408 TI - Temperature-responsive solid-liquid separations with charged block-copolymers of poly(N-isopropyl acryamide). AB - Temperature responsive charged block-copolymers of poly(N-isopropylacrylamide) (PNIPAM) have been used in the solid-liquid separation of alumina mineral particles from aqueous solution. The effects of temperature, polymer charge-sign and fraction of charged segment have been investigated. Batch settling and adsorption studies showed that rapid sedimentation results for suspensions with polymers of opposite charge-sign to the particle surface-charge (counterionic) at 50 degrees C. Cooling the suspensions after flocculation at 50 degrees C was found to increase the final solids volume fraction of the sediment beds formed through a mechanism related to partial desorption of polymer and the reduction of the hydrophobic attraction. Suspension stability results after dosing with polymers of similar charge-sign to the particle surface-charge (co-ionic) at both 25 and 50 degrees C. Increasing the amount of polymer charge increased the influence of polymer charge-sign on the adsorption and solid-liquid separation behavior. The performance of the charged block copolymers are compared to that of the random charged copolymer and neutral homopolymer PNIPAM structures. PMID- 22070409 TI - The selective phosphodiesterase 9 (PDE9) inhibitor PF-04447943 attenuates a scopolamine-induced deficit in a novel rodent attention task. AB - Numerous changes occur during aging and Alzheimer's disease (AD) progression, including a decline in cholinergic functioning and cognition, as well as alterations in gene expression and activity in the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway. Donepezil, the current standard of care for Alzheimer's disease, improves cholinergic functioning and has demonstrated effects on multiple domains of cognition, including memory and attention in both preclinical species and patients. We previously found that increasing activation of the NO/cGMP pathway via phosphodiesterase 9 (PDE9) inhibition also improves memory in rodents and suggested that PDE9 might be a promising target for novel treatments for AD. Here we investigated whether PDE9 inhibition also enhances attention using a novel attention task in rats. We validated this task using several pharmacological manipulations and showed that the selective PDE9 inhibitor PF-04447943 produced effects similar to those of donepezil. These data confirm and extend the hypothesis that PDE9 inhibition might serve as a novel treatment for AD and age-related cognitive decline. PMID- 22070410 TI - Effect of antioxidants on oxidation during the production of whey fat concentrate. AB - Whey fat has a relatively high level of unsaturated fatty acids, and as such, whey products with a high fat content are vulnerable to oxidation. The purposes of the present study were to assess the oxidative development in whey fat concentrate (WFC) during production and investigate the effect of the addition of antioxidants. Green tea extract (GTE) or a mixture of ascorbyl palmitate and tocopherol (AP/TOC) were used, each in two concentrations. Samples were taken before and after pasteurization of WFC and after drying. The level of volatile oxidation products decreased during processing, while dityrosine concentrations increased during drying. GTE reduced oxidation in both unpasteurized and pasteurized WFC, while the effect of AP/TOC was nonsignificant. In the WFC powder, there was no significant effect of the antioxidants. In conclusion, results indicated that GTE was able to inhibit oxidation in WFC during production and that AP/TOC addition had no effect. PMID- 22070411 TI - Tubal ligation and survival of ovarian cancer patients. AB - AIM: The aim of the present study was to investigate associations between ovarian cancer survival and reproductive, gynecological and hormone factors. MATERIAL AND METHODS: A prospective follow-up study was conducted in the Southeast of China. The cohort comprised 202 patients with histopathologically confirmed epithelial ovarian cancer who were enrolled during 1999-2000 and followed-up for 5years subsequently. One hundred and ninety five (96.5%) of the cohort or their close relatives were traced. Information was obtained on reproductive, gynecological and hormone factors prior to diagnosis, actual survival time and number of deaths. Cox proportional models were used to estimate mortality hazard ratios (HR) and associated 95% confidence intervals (CI) for tubal ligation, adjusting for age at diagnosis, body mass index (BMI), menopausal status, International Federation of Gynaecology and Obstetrics (FIGO) stage, histological grade of differentiation, cytology of ascites, and chemotherapy status. RESULTS: The HR was significantly increased and survival was worse in ovarian cancer patients with a previous tubal ligation, but not with any other reproductive, gynecological and hormone factor. Only 21 (38.9%) of 54 patients who had tubal ligation survived to the time of interview, in contrast to 95 women (67.4%) still alive among the 141 women without tubal ligation (P<0.001). Compared to the patients who had no tubal ligation, the adjusted HR was 1.62 (95% CI 1.01-2.59; P=0.04) for those who had tubal ligation. There was no association with age at menarche, menopausal status, parity, breastfeeding, hormone replacement therapy, oral contraceptive use, and hysterectomy. CONCLUSION: Previous tubal ligation was an independently adverse prognostic factor for epithelial ovarian cancer survival. Further studies that examine the relationship are warranted to confirm these results. PMID- 22070412 TI - Gene expression profile of lymphatic endothelial cells. AB - The lymphatic system was first described at around the same time as the blood circulation centuries ago, but the biological function elucidation of LECs (lymphatic endothelial cells) is far less than that of BVECs (blood vascular endothelial cells). Since the discovery of molecular markers for LECs and exploration of lymphatic role in tumour metastasis, more attention has been given to basic lymphatic research. Approx. 150 known genes were found to be expressed at the mRNA and protein levels by LECs. These molecules play an important role in lymphangiogenesis, signalling, tumour metastasis, immune function and fluid transport. This review provides a brief outline of gene expression profile of LECs and the molecular biological function, which will give the reader a better understanding about the mechanics of lymphatic function and some pathologies related to the lymphatic system such as lymphoedema, and facilitate advanced scientific research into lymphatic biology. PMID- 22070414 TI - Managing risk: a qualitative study of community-based professionals working with learning-disabled sex offenders. AB - This study reports on research conducted to examine how community practitioners manage the difficulties of risk assessment in relation to people with a learning disability and a history of sexually offensive or abusive behaviour. Semi structured interviews were conducted with a number of key professionals from various disciplines, all currently involved in the assessment process with the aim of determining potential referral to community settings. Data analysis revolved around a thematic exposition of factors influencing the relationship between the objective science of psychiatric investigation and the subjective interpretation of real-world practicalities in working with this group. Findings surrounded three major themes, frame conflict, relating to the difficulties of decision making in this area, therapeutic performance, whereby professionals were expected to engage in some form of active intervention, and safety outcomes, involving consideration of the problematic nature of judging the likelihood of re offending. PMID- 22070413 TI - On the possible use of exogenous histones in cell technology. AB - The prospect of developing transport systems using histones for site-specific delivery of therapeutic agents that have poor penetration characteristics through cellular membranes and tissue barriers has been investigated. Histones immobilized on microspheres can also be used to modify surfaces intended for cell cultivation, facilitating adhesion, proliferation and network formation by interactions of cells through contacts with several microspheres. They can be applied to three-dimensional pore matrices that are designed for producing tissue like structures in vitro. PMID- 22070415 TI - Negative support of significant others affects psychological adjustment in breast cancer patients. AB - Significant others play an important role in providing support in patients' lives, but some types of support negatively affect the patients. This study was conducted in early-stage breast cancer patients to examine the structure of support, which was provided by their significant others and assessed negatively by the patients, and to identify negative support relating to the psychological adjustment of these patients. Thus, we first conducted interviews among 28 breast cancer patients to identify these support items assessed as negative; next, we conducted a questionnaire survey using the resulting items in 109 postoperative patients who had early-stage breast cancer. We performed exploratory and confirmatory factor analyses and obtained a valid second-order factor structure, including superordinate factors (excessive engagement, avoidance of problems and underestimation) and subordinate factors (overprotection, encouragement and management). Among these factors, the avoidance of problems was the only factor to be negatively associated with psychological adjustment of the patients, suggesting that these patients receive problem-avoiding support. The results of our study suggest that such problem-avoiding support from significant others can be counter-productive and potentially worsen the psychological adjustment of breast cancer patients. PMID- 22070416 TI - The role of perceived benefits and costs in patients' medical decisions. AB - BACKGROUND: Many decisions can be understood in terms of actors' valuations of benefits and costs. The article investigates whether this is also true of patient medical decision making. It aims to investigate (i) the importance patients attach to various reasons for and against nine medical decisions; (ii) how well the importance attached to benefits and costs predicts action or inaction; and (iii) how such valuations are related to decision confidence. METHODS: In a national random digit dial telephone survey of U.S. adults, patients rated the importance of various reasons for and against medical decisions they had made or talked to a health-care provider about during the past 2 years. Participants were 2575 English-speaking adults age 40 and older. Data were analysed by means of logistic regressions predicting action/inaction and linear regressions predicting confidence. RESULTS: Aggregating individual reasons into those that may be regarded as benefits and those that may be regarded as costs, and weighting them by their importance to the patient, shows the expected relationship to action. Perceived benefits and costs are also significantly related to the confidence patients report about their decision. CONCLUSION: The factors patients say are important in their medical decisions reflect a subjective weighing of benefits and costs and predict action/inaction although they do not necessarily indicate that patients are well informed. The greater the difference between the importance attached to benefits and costs, the greater patients' confidence in their decision. PMID- 22070417 TI - Reviews on animal diseases recently published in other journals. PMID- 22070419 TI - Weight status and health characteristics of rural Saskatchewan children. AB - INTRODUCTION: The present and future health of children is significantly threatened by physical inactivity, poor diet, and the obesity epidemic. Limited studies on the health of children living in rural settings suggest that rural children have a higher prevalence of overweight and may not be as active as their urban counterparts. The purpose of this study was to examine the health behaviors and weight status of children aged 8 to 13 years living in rural Saskatchewan, Canada. METHODS: A cross-sectional health questionnaire assessed the health behaviors (eg physical activity, sedentary behaviors, dietary patterns) and perception of health status (eg very healthy, quite healthy, not very healthy) of 99 children attending a rural school. Heights and weights were measured and used to calculate BMI's (kg/m2). The BMIs were used to categorize children as healthy weight, overweight, or obese. RESULTS: Thirty-four percent of children were overweight (23.7%) or obese (10.3%) with a significantly higher prevalence of overweight/obesity in boys aged 6 to 8 years (p <0.05). A significantly higher proportion of children living in town (vs living on a farm) watched two or more hours of television a day (p <0.05). Many children (65%) used active transport (bus or car) to school or after-school activities. The majority of children reported they were very healthy. Most children reported eating fruit and vegetables more frequently, and sugared drinks and French fries less frequently. CONCLUSION: Prevalence of overweight/obesity in these rural children was high with gender differences evident at a very young age. Most children reported eating healthy diets but many participated in several hours of daily 'screen time' (eg watching television or using a computer). Despite their weight status or patterns of physical inactivity, children perceived themselves as being very healthy. Understanding the health behaviors and weight status of rural children may assist in the development of effective health promotion programs for rural children. PMID- 22070420 TI - Models of care delivery in mental health nursing practice: a mixed method study. AB - The aim of this study was to identify the conceptual models that underpin mental health nursing care in clinical settings. This study is a modification of a previous study which evaluated the influence of implicit models of mental disorder on processes of decision making within community-based teams. Participants completed questionnaires in response to a scenario. A range of explanatory conceptual models were identified in respect to aetiology, treatment and recovery. In a forced choice the participants ranked a medical model of care above other models as underpinning care delivery. The content analysis found that the participants used a psychodynamic framework for understanding the causes of mental distress but described the nursing interventions in terms of supporting a medical model of care. Nursing care is dominated by a medical model which constrains mental health nursing. This potentially creates tension between what nurses believe to be the problem and the responses available for nurses in their clinical setting. A range of psychosocial approaches to mental health care delivery have been developed, but there seems to be problems with their implementation in practice. Further research is required to explore how broader therapeutic interventions can be implemented by nurses within multidisciplinary systems of mental health care delivery. PMID- 22070422 TI - Acne: prevalence and relationship with dietary habits in Eskisehir, Turkey. AB - BACKGROUND: Acne vulgaris is a common disease affecting adolescents. There is not comprehensive data on acne prevalence in the Central Anatolia Region in particular. Etiology of acne is not clarified yet. Acne might be related to environmental factors. There is increasing evidence supporting acne and diet relationship. OBJECTIVES: The aim of the study was to determine the acne prevalence in adolescents in the city of Eskisehir, located in the Central Anatolia, Turkey in addition to evaluate factors affecting acne and its relationship with dietary habits. METHODS: A cross-sectional study was conducted on 2300 participants aged 13-18 years. The participants were asked to complete a questionnaire form consisting information about acne and a questionnaire form consisting information about dietary habits (The Adolescent Food Habits Checklist). In addition an objective evaluation of acne was determined. RESULTS: The mean age of students with acne was 15.10+/-1.53. The current acne prevalence was 60.7%. Although 21% of the participants had severe acne (grade 3-4) and 25% developed sequelaes, only 11.5% of all participants consulted a doctor. The participants without acne had healthier dietary habits than participants with acne (P<0.05). Frequent fat intake (OR=1.39, 95% CI: 1.06-1.82), frequent sugar intake (OR=1.30, 95% CI: 1.05-1.60), frequent eating sausages, burgers (OR=1.24, 95% CI: 1.03-1.48), frequent eating pastries, cakes (OR=1.20, 95% CI: 1.01-1.43) were associated with increased risk for acne. CONCLUSIONS: Acne prevalence is high among adolescents in Eskisehir but the rate of consulting doctor is low. Increasing public awareness is critical for convincing adolescents to seek medical help earlier. Acne was related with dietary habits. Fat, sugar and fast food consumption is found to be positively correlated with acne prevalence. PMID- 22070421 TI - Is response to OROS-methylphenidate treatment moderated by treatment with antidepressants or psychiatric comorbidity? A secondary analysis from a large randomized double blind study of adults with ADHD. AB - AIMS: The main aim of this post hoc analysis was to evaluate whether response to osmotic release oral system (OROS) methylphenidate (OROS-MPH) was moderated by the concomitant use of antidepressants in attention-deficit/hyperactivity disorder (ADHD) adults stabilized on these medicines for the treatment of depression or anxiety disorders, or a history of mood, anxiety, or substance use disorders. METHODS: Two hundred and ninety-six subjects were screened for participation; 227 were randomized (112 to OROS-MPH and 115 to placebo), and 223 were analyzed (N= 109 and N= 114 for OROS-MPH and placebo, respectively). Subjects with anxiety disorders and depression treated with a stable medication regimen of non-MAOI antidepressants or benzodiazepines for at least 3 months could be enrolled in the study. Subjects currently receiving pharmacotherapy for anxiety disorders or depression were required to have Hamilton-Depression and Hamilton-Anxiety rating scales below 15 (mild range). RESULTS: Concomitant antidepressant use at baseline was not associated with ADHD response, OROS-MPH dose, study completion rate, adverse effects, or exacerbation of anxiety/depression. We did find nominally significant evidence that a lifetime history of mood (P= 0.09) or anxiety (P= 0.04) disorders was a moderator of ADHD symptoms and that a lifetime history of substance use disorder (P= 0.02) was a potential moderator of dose at endpoint. DISCUSSION AND CONCLUSIONS: We found few moderating effects in this large clinical trial of OROS-MPH in adults with ADHD, which supports the robustness of the clinical response to OROS-MPH in adult ADHD despite variable clinical pictures. PMID- 22070423 TI - Patient satisfaction as an outcome of individualised nursing care. AB - BACKGROUND: The association between individualised nursing care and patient satisfaction has been previously found. However, there is a lack of studies examining this association between individualised care and patient satisfaction in a cross-cultural study. AIMS: This study examines the association between individualised care and patient satisfaction in a sample of general surgical patients from five European countries. METHODS: A cross-sectional design and survey method were used to collect data from general surgical patients (N = 1315, response rate 78%) in 72 inpatient wards in 26 general acute hospitals' in 2009 using self-completed questionnaires the Individualised Care Scale and the Patient Satisfaction Scale. Data were analysed using descriptive statistics, Pearson correlation coefficients and multiple stepwise regression analyses. RESULTS: Surgical patients reported that the care they received was only moderately individualised overall, but individuality was taken into account well in patients' clinical situation and decisional control over care. Patients were satisfied with their care, mostly with the technical aspects of care and least with the information given. There were between-country differences in patients' perceptions of individuality in care and patient satisfaction. A positive correlation between the level of individualised care received and patient satisfaction was found, confirming that individualised nursing care delivery influences patients' satisfaction with care and demonstrating that this quality of care indicator might be able to be used as a predictor of patient satisfaction, one outcome of care. CONCLUSION: The findings of this study strengthen previous results and further reporting the existence of a relationship and the positive correlation between individualised care and patient satisfaction. The results can inform administrative decisions and policy on introducing nursing approaches to care that would increase patient satisfaction. PMID- 22070425 TI - Profile of inflammatory mediators in gestational diabetes mellitus: phenotype and genotype. AB - PROBLEM: Our study aimed to assess in vitro production of IL-10, IL-6, TNF-A, and adiponectin serum levels in pregnant women with and without gestational diabetes mellitus (GDM) and to investigate a possible association between GDM and IL-10 1082 A>G (rs1800896), IL-6-174 G>C (rs1800795), TNF-A-308 G>A (rs1800629), adiponectin +45 T>G (rs2241766), and adiponectin-11377 C>G (rs266729) gene polymorphisms. METHOD OF STUDY: This case-control study included 79 women with GDM and 169 healthy controls (C) grouped according to pre-pregnancy BMI. IL-10, IL-6, and TNF-A culture supernatant and adiponectin serum levels were assessed by ELISA. DNA genotype was performed by PCR-RFLP. RESULTS: Adiponectin levels were significantly higher in C than GDM women, even within the same BMI category. Cytokines levels were similar between the groups. There were no associations between GDM and the analyzed gene polymorphisms. CONCLUSIONS: Women with GDM have significantly lower adiponectin levels in the third trimester, regardless of BMI. PMID- 22070424 TI - Proteome driven re-evaluation and functional annotation of the Streptococcus pyogenes SF370 genome. AB - BACKGROUND: The genome data of Streptococcus pyogenes SF370 has been widely used by many researchers and provides a vast array of interesting findings. Nevertheless, approximately 40% of genes remain classified as hypothetical proteins, and several coding sequences (CDSs) have been unrecognized. In this study, we attempted a shotgun proteomic analysis with a six-frame database that was independent of genome annotation. RESULTS: Nine proteins encoded by novel ORFs were found by shotgun proteomic analysis, and their specific mRNAs were verified by reverse transcriptional PCR (RT-PCR). We also provided functional annotations for hypothetical genes using proteomic analysis from three different culture conditions that were separated into three fractions: supernatant, soluble, and insoluble. Consequently, we identified 567 proteins on re-evaluation of the proteomic data using an in-house database comprising 1,697 annotated and nine non-annotated CDSs. We provided functional annotations for 126 hypothetical proteins (18.9% out of the 668 hypothetical proteins) based on their cellular fractions and expression profiles under different culture conditions. CONCLUSIONS: The list of amino acid sequences that were annotated by genome analysis contains outdated information and unrecognized protein-coding sequences. We suggest that the six-frame database derived from actual DNA sequences be used for reliable proteomic analysis. In addition, the experimental evidence from functional proteomic analysis is useful for the re-evaluation of previously sequenced genomes. PMID- 22070426 TI - Adolescent client views towards the treatment of anorexia nervosa: a review of the literature. AB - This paper reviews current literature in which adolescents with anorexia nervosa (AN) were consulted about their views of their treatment. Published research was systematically retrieved and interrogated during 2009-2010 and analysed using a four-stage model. Eleven studies met the inclusion criteria. Three core themes were identified. AN was perceived as a means of taking control and also something that controlled the individual. Tensions were recognized between client preferences for psychological interventions and treatments that prioritized physical care. Therapeutic alliance emerged as a strategy for overcoming these difficulties but was challenged by client ambivalence towards treatment. Most included studies were qualitative. Young males and individuals who dropped out of treatment were underrepresented in the studies. Adolescents' perspectives on treatment for AN were characterized by paradoxes and tensions. Egosyntonic theory was used as a theoretical construct to interpret findings. PMID- 22070427 TI - Early age-related macular degeneration in patients with myocardial infarction. AB - PURPOSE: To investigate the prevalence of early age-related macular degeneration (AMD) in patients with acute myocardial infarction (MI). METHODS: Enrolled in the study were 262 acute MI patients (MI group), aged 40-64 years, as well as 1,155 non-MI persons, aged 40-64 years, from a random sample (reference group) of the Kaunas population. RESULTS: The prevalence of early AMD in the random sample was 7.3%, while in MI patients, the prevalence was 54.5% (P < 0.001). For all age groups, the prevalence of early AMD was significantly (P < 0.005) higher in MI patients than in reference-group persons. In the reference group, the prevalence of early AMD increased significantly with age, whereas no such trend was observed in the MI group. At the 45- to 54-year-olds, the prevalence was significantly higher in males than in females (9.9% vs. 3.7%; P < 0.05) in the reference group, while overall, the prevalence of early AMD in the males and females of the much larger reference group was 8.6% versus 6.2%, respectively (P > 0.05). It increased more with age for females (3.7% and 10.8% at the age 45-54 and 55-64 years, P < 0.05, respectively) while in males, frequency of AMD did not differ significantly between latter age groups (9.9% vs. 11.6%; P > 0.05). CONCLUSIONS: We conclude that the prevalence of early AMD is significantly higher in patients with MI than in a random sample of the population. PMID- 22070428 TI - Recent history provides sustainable African water quality project insight. AB - Small-scale projects to provide clean drinking water undertaken in the developing world can contribute to significantly improving the livelihood of rural communities. There has been a historical tendency to poorly plan such projects leading to an unsustainable future. Recent history indicates three simple steps to ensuring successful and enduring clean water projects. First, identification of need by the indigenous community provides ownership in the project. Second, a partnership between key individuals in the indigenous community with the donor provides for ambassadors on both sides of the project. Finally, an exit strategy by the donors for the indigenous communities ensures local sustainability for the future. The study site is the village of Geisha in northern Malawi, Africa. Sustainable implementation approaches are discussed in this case study as well as the various lessons learned. Improved project processes ensure sustainable small scale water quality projects by donor organizations in developing countries. PMID- 22070429 TI - Acupuncture for anxiety. AB - This review aims to examine the volume and quality of the evidence base which supports the use of acupuncture in the treatment of anxiety disorders. A literature review was conducted using Pubmed, Google scholar, AMED, BMJ, Embase, Psychinfo, Cochrane library, Ingenta connect, and Cinahl databases. Keywords were "anxiety,""anxious,""panic,""stress,""phobia," and "acupuncture" limited to year 2000 onwards and English language where available. The quality of research examining the use of acupuncture in the treatment of anxiety disorders is extremely variable. There is enormous variety regarding points used, number of points used in a session, duration of sessions, frequency of treatment and duration of treatment programme. While the generally poor methodological quality, combined with the wide range of outcome measures used, number and variety of points, frequency of sessions, and duration of treatment makes firm conclusions difficult. Against this, the volume of literature, consistency of statistically significant results, wide range of conditions treated and use of animal test subjects suggests very real, positive outcomes using a treatment method preferred by a population of individuals who tend to be resistant to conventional medicine. PMID- 22070431 TI - Film stability during postassembly morphological changes in polyelectrolyte multilayers due to acid and base exposure. AB - The mechanism of the transition from a continuous morphology to a porous morphology within polyelectrolyte multilayers (PEMs) of linear poly(ethylene imine) (LPEI) and poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH) and PAA assembled by the layer-by-layer (LbL) technique is examined. These morphological changes were created by both acidic and basic postassembly treatments. Basic postassembly treatment is shown to create different types of porosity than acidic postassembly treatment. The morphological variation from the introduction of porosity to the collapse of these porous structures and the dissolution of films under postassembly treatments was observed by AFM, optical microscopy, quartz crystal microbalance (QCM), and SEM. These morphological transitions which are a result of structural rearrangement of weak polyelectrolytes due to pH changes are closely related to the neutralization of the polycations and the ionization of polyanions. Results obtained from FTIR spectroscopy and QCM confirm that polyelectrolytes are being selectively or partially released from the polyelectrolyte multilayers thin films (PEMs) in response to the pH treatment as a function of exposure time. In conclusion, here new information is presented about the structural reorganization found in a number of weak polyelectrolyte systems. This information will be useful in designing functional materials based on polyelectrolytes. PMID- 22070433 TI - Comment on "Optimized preprocessing of ultra-performance liquid chromatography/mass spectrometry urinary metabolic profiles for improved information recovery". PMID- 22070432 TI - Membrane-assisted online renaturation for automated microfluidic lectin blotting. AB - Aberrant glycosylation plays a pivotal role in a diverse set of diseases, including cancer. A microfluidic lectin blotting platform is introduced to enable and expedite the identification of protein glycosylation based on protein size and affinity for specific lectins. The integrated multistage assay eliminates manual intervention steps required for slab-gel lectin blotting, increases total assay throughput, limits reagent and sample consumption, and is completed using one instrument. The assay comprises non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by online post-sizing SDS filtration and lectin-based affinity blotting. Important functionality is conferred through both device and assay advances that enable integration of nanoporous membranes flanking a central microchamber to create sub-nanoliter volume compartments that trap SDS-protein complexes and allow electrophoretic SDS removal with buffer exchange. Recapitulation of protein binding for lectin was optimized through quantitative assessment of SDS-treated green fluorescent protein. Immunoglobulin A1 aberrantly glycosylated with galactose-deficient O glycans was probed in ~6 min using ~3 MUL of sample. This new microfluidic lectin blotting platform provides a rapid and automated assay for the assessment of aberrant glycosylation. PMID- 22070434 TI - Toll-like receptors and diabetes: a therapeutic perspective. AB - Diabetes is a mutifactorial metabolic disorder that leads to a number of complications. Diabetes is estimated to affect 36 million people in the U.S.A., and the prevalence of diagnosed and undiagnosed diabetes is at 9.3% and continues to rise. Evidence from experimental animal models as well as humans has indicated that systemic inflammation plays a role in the pathophysiological processes of diabetes and is facilitated by innate immune responses. TLRs (Toll-like receptors) are key innate immune receptors that recognize conserved PAMPs (pathogen-associated molecular patterns), induce inflammatory responses essential for host defences and initiate an adaptive immune response. Although TLR expression is increased in a plethora of inflammatory disorders, the effects of metabolic aberrations on TLRs and their role in diabetes and its complications is still emerging. In the present paper, we provide a systematic review on how TLRs play a detrimental role in the pathogenic processes [increased blood sugar, NEFAs (non-esterified 'free' fatty acids), cytokines and ROS (reactive oxygen species)] that manifest diabetes. Furthermore, we will highlight some of the therapeutic strategies targeted at decreasing TLRs to abrogate inflammation in diabetes that may eventually result in decreased complications. PMID- 22070435 TI - Equal access for Medicaid beneficiaries--the Supreme Court and the Douglas cases. PMID- 22070436 TI - Great expectations: a systematic review of the literature on the role of family carers in severe mental illness, and their relationships and engagement with professionals. AB - As community care has become embedded in the U.K. as in much of the western world more responsibility for psychosocial care has been placed on family carers. A systematic review of the literature about the role of family carers supporting a relative with severe mental illness and their relationships and engagement with professionals was carried out. The review aimed to find out what professionals expected of family carers and what family carers expected of themselves. Themes were identified: the distinct and personal nature of family caring, potentially effective family caring, barriers to effective caring and ways to overcome barriers. There were expectations that family carers were obligated to help support effective care, but that the rights to enable carers to fulfil these obligations were not consistently upheld. Barriers to upholding rights include: types of service provision, professional attitudes to communication and engagement with carers, and carer ability to cope. Recommendations for practice included: service provision aimed at including carers, more empathic communication by professionals, and a covenant between mental health services and people who depend on them. The idea of a covenant requires more discussion and research is needed into what is expected of family carers. PMID- 22070437 TI - Naturopathic medicine and public health: teaming up for a transformative tomorrow. PMID- 22070439 TI - The intersecting paradigms of naturopathic medicine and public health: opportunities for naturopathic medicine. AB - Complementary medicine research, including naturopathic medicine research, is plagued with many methodological challenges. Many of these challenges have also been experienced in public health research. Public health research has met these challenges with a long history of multidisciplinary, multimethod, and whole systems approaches to research that may better resonate with the ?real world? clinical settings of naturopathic medicine. Additionally, many of the underlying principles of naturopathic medicine are analogous to the underlying principles and activities of public health, specifically in such areas as health promotion, prevention, patient education, and proactive rather than reactive approaches to disease management and treatment. Future research in the field of naturopathic medicine may benefit from adopting public health research models rather than focusing exclusively on biomedical models. A complementary and collaborative relationship between these fields may provide an opportunity to deliver research that more accurately reflects naturopathic medicine practice, as well as providing the opportunity to improve health outcomes more generally. PMID- 22070438 TI - Reduced health resource use after acupuncture for low-back pain. AB - OBJECTIVES: Acupuncture is commonly used to treat low-back pain (LBP) and clinical trials have demonstrated its efficacy. However, less is known about how the utilization of acupuncture impacts public health service utilization in the real world. This study investigates the association between acupuncture utilization for LBP and health care utilization by assessing whether patients who undergo acupuncture subsequently use fewer health care resources and whether those patients differ in their health care use from the general population with LBP. DESIGN: This study employed the design of a two-group pre/post secondary data analysis. SETTING AND SUBJECTS: There were two study populations. To identify patients who received acupuncture for LBP in 2000, patient charts at Alberta registered acupuncture clinics were reviewed. The comparison group was identified from the Alberta physician claims administrative database. Acupuncture group cases were matched with four comparison cases from the general population with LBP based on gender and age. OUTCOME MEASURES: Number of physician visits and physician service cost for LBP-related services for 1 year pre- and postacupuncture treatment period were calculated from the physician claims data for both study groups. RESULTS: For the 201 cases and 804 controls, the mean age was 48 years and 54% were female. The number of physician visits for the 1-year period postacupuncture decreased 49% for the acupuncture group (p<0.01) compared to the 1-year period preacupuncture. For the comparison there was a decrease of 2% in physician visits (p=0.59) for the same time periods. Corresponding to the decrease, physician services cost declined 37% for the case group (p=0.01) and 1% for the comparison (p=0.86). CONCLUSIONS: Results suggest that patients with LBP were less likely to visit physicians for LBP after acupuncture treatment. This led to reduced health services spending on LBP. PMID- 22070441 TI - A case of aromatase inhibitor (anastrozole)-induced side-effects successfully treated with Kampo medicines. AB - OBJECTIVES: Breast cancer is the fourth most frequent cause of death, and it is currently the most frequent cause of death among Japanese women. As to breast cancer therapy, lengthy hormonal therapy is very important for the treatment and prevention of recurrence. Aromatase inhibitors (AIs) are the initial drug of choice for postoperative adjuvant therapy of breast cancer in Japan. AIs require long-term use and occasionally cause serious side-effects. In this report, the effects of Kampo medicines (Japanese traditional medicines) on AIs-induced side effects are described. SUBJECT: A 55-year-old woman visited the Kampo outpatient department of Chiba University Hospital for atypical genital bleeding and arthralgia. At the age of 54, she suffered from left breast cancer and underwent left total mastectomy followed by chemotherapy for 6 months. Afterwards, 1 mg/day of anastrozole, one of the AIs, was used for therapy. Three (3) months later, atypical genital bleeding from vaginal mucosa and joint pains of bilateral hands and knees occurred as side-effects of anastrozole. Her attending doctor could only prescribe nonsteroidal external medicine for the inflammation of vaginal mucosa and do close follow-up. However, her symptoms showed no improvement. INTERVENTIONS AND OUTCOME: Her deficiency of both ki (qi) and ketsu (Blood) was diagnosed based on Kampo diagnostics. Juzentaihoto was used for treatment. After taking juzentaihoto for 5 weeks, the atypical genital bleeding disappeared, and she no longer need topical medicine. Because her arthralgia showed no improvement, powdered processed aconitine root was added. After taking 3.0 g/day of this medication, her arthralgia almost completely disappeared. CONCLUSIONS: Controlling the side-effects is a clinical issue from the viewpoint of adherence to drug treatment. Kampo therapy should be considered one of the choices for side effects in the process of cancer treatment. PMID- 22070442 TI - The relationship between dental occlusion/temporomandibular joint status and general body health: part 1. Dental occlusion and TMJ status exert an influence on general body health. AB - BACKGROUND: There have been varied studies that have suggested a relationship between dental occlusion/temporomandibular joint (TMJ) status and general body health. Therefore, it is important to elucidate the systematic relationships and corresponding action mechanisms between them. OBJECTIVES: The purpose of this part of study was to review the relationships between dental occlusion/TMJ status and systemic body health based on the published literature. METHODS: This study, based mostly on peer-reviewed specialist articles, has determined that dental occlusion/TMJ status exerts an influence on (1) synchronization of head and jaw muscles with the muscles from other body sites for proper body posture; (2) body stability such as body equilibrium (balance), center of gravity fluctuation, and gaze stability; and (3) physical performance along with physical fitness. CONCLUSIONS: Therefore, these relationships should be further investigated and extended to the whole body, and the action mechanisms should be elucidated. PMID- 22070443 TI - Attitude of conventional and CAM physicians toward CAM in India. AB - OBJECTIVES: The aim of the present study was to compare the attitude toward complementary and alternative medicine (CAM) of primary care physicians trained in conventional medicine with CAM physicians whose training was for a comparable duration. The CAM physicians included practitioners of Ayurveda, homeopathy, and naturopathy. PARTICIPANTS: Two hundred and ninety five (295) physicians with aged 20-60 (group mean+/-standard deviation, 48.2-12.3 years, 87 females) participated. Eighty-six (86) of them were trained in Ayurveda, 90 in homeopathy, 82 in conventional medicine, and 37 in naturopathy. They were attending a 4-day residential program on Indian culture. All of them gave their signed consent to take part in the study, and the institution's ethics committee approved the study. STUDY DESIGN: The study was a cross-sectional survey. Since the participants had self-selected to join for the program on Indian culture, the sampling could be considered as convenience sampling. RESULTS: The number of conventionally trained and CAM physicians were similar in number and in their reasons for selecting CAM treatments. CONCLUSIONS: Conventionally trained and CAM physicians were comparably likely to prescribe CAM treatments for their patients. Their reasons for prescribing CAM treatments appeared to be (1) the idea that CAM treatments deal with the cause, and (2) a belief in the treatments. A limiting factor of the survey is that it did not determine whether the belief was based on evidence or on faith alone. PMID- 22070444 TI - Clinical handover in acute psychiatric and community mental health settings. AB - This study collected an area-wide snapshot of current handover practice in psychiatric settings which included acute care units and community mental health centres. The study was conducted in two stages. Firstly, a questionnaire was sent to all clinical mental health staff within an area-wide health service regarding normal handover procedures and processes. The second part of the study used non participant observers to evaluate actual handovers in inpatient and community settings. Of the 1125 surveys distributed in stage one, 380 (34%) were returned completed. Of the 40 handovers observed in stage two in which 637 patients were discussed, 40% included at least one consultant psychiatrist or registrar as a participant. Almost all the handovers were completed face-to-face in a specific location with a set time and duration. Eighty-six per cent of respondents reported that deteriorating patients were escalated for rapid response. The results of the survey and structured observations support the issues emerging from the literature from medical, surgical and clinical team handovers. Additionally, the issue of identifiers for deterioration of a psychiatric patient emerged as an area worthy of further investigation and incorporation into clinical handover education and training for psychiatric services. PMID- 22070445 TI - Developing written information on osteoarthritis for patients: facilitating user involvement by exposure to qualitative research. AB - INTRODUCTION: In developing a guidebook on osteoarthritis (OA), we collaborated with people who have chronic joint pain (users). But to advise, users need to be aware of and sensitive about their own state of knowledge and educationalists argue that adults sometimes lack such awareness. This paper will report on our experience of providing users with findings from qualitative research to increase awareness of their level of knowledge. METHOD: A summary of the results from qualitative research into people's experiences of living with chronic pain was sent to individual members of two groups of users. It was then used to structure group meetings held to help identify information needed for the guidebook. FINDINGS: Some users found the summary difficult to read and suggested how to simplify it. Nevertheless, it helped most users to become aware of the experiences and views of others who have OA and thus become more sensitive to their own level of knowledge. It also helped them recall experiences that stimulated practical suggestions for managing joint pain in everyday life and provided a way of gently challenging the views of users when they appeared to assume that their views were widely held. The discussions brought to light gaps in the research literature. CONCLUSION: We believe this way of involving users by exposing them to qualitative research findings about lay experiences of living with OA effectively facilitated the users' contributions to the needs of those who have to live with OA, and we believe it has wider applications. PMID- 22070446 TI - Efficacy of passive uterine straightening during intrauterine insemination on pregnancy rates and ease of technique. AB - AIM: The aim of the present study was to evaluate the efficacy of passive uterine straightening during intrauterine insemination (IUI). MATERIAL AND METHODS: A randomized controlled trial was conducted at Zeynep Kamil Maternity and Pediatric Research and Training Hospital. Participants were 460 women with unexplained infertility. Interventions were IUI by passive straightening of the uterus by means of bladder filling, or IUI performed with an empty bladder. Main outcome measures included pregnancy rate and difficulty of IUI. RESULTS: Four hundred and sixty couples were allocated: 230 couples were allocated to the full bladder group, and 230 couples were allocated to the empty bladder group (control). The pregnancy rate was higher in the full bladder group than in the empty bladder (control) group (P=0.03, 13.5% vs 7.4%; relative risk [RR] 1.95 for pregnant patients; 95% confidence intervals [CI] 1.048-3.637). The risk of undergoing difficult IUI was higher in the empty bladder group than the full bladder group (P<0.001; 10.0% vs 37.8%, RR 0.18 for difficulty IUI; 95% CI 0.11-0.30). The clinical pregnancy rate was also higher in the group of patients who had easy IUI than in the group of patients who had difficult IUI (P<0.05, 12.7% [42/331] vs 5.5% [6/110]); RR 2.51 for pregnancy; 95% CI 1.04-6.09). CONCLUSION: Passive straightening of the uterus makes the procedure less difficult and improves the clinical pregnancy rate. PMID- 22070447 TI - Health and well-being as drivers of global success. PMID- 22070448 TI - Concern as motivation for protection: an investigation of mothers' concern about daughters' breast cancer risk. AB - The present study surveyed mothers with daughters (N = 386) to investigate how mothers' concern about their daughters' breast cancer risk influenced intentions to engage in preventive behaviors. Using protection motivation theory as a framework, self-efficacy, response efficacy, and level of concern were posited to influence protective behavioral intention in distinct ways. Results from regression analyses indicate that self-efficacy, response efficacy, and mothers' concern are significant predictors of intentions to engage in preventive behaviors with daughters. In addition, a content analysis of mothers' open-ended reasons for their concern about their daughters' breast cancer risk yield a list of specific concerns and trends that vary by concern level and individual comment valence. The authors discuss implications for incorporating mothers' concerns into breast cancer prevention messages as a novel strategy for campaign designers. PMID- 22070449 TI - Predictors of supportive message expression and reception in an interactive cancer communication system. AB - Social support in computer-mediated settings is an important variable in health communication research, yet little is known about the factors that influence the amount of social support one gives and receives in online support groups. To shed some light on this issue, the authors examined demographics, disease-related factors, psychosocial factors, and strategies for coping with breast cancer as potential determinants of which patients provide support to others and which ones consume it. Data collected from 177 participants in the Comprehensive Health Enhancement Support System "Living With Breast Cancer" program revealed that individuals who are younger, have higher levels of positive reframing, and lower levels of self-blame are more likely to provide emotional support in online settings. In contrast, individuals who are more educated, have less perceived availability of social support, and have lower levels of religious coping are more likely to receive emotional support from others. The authors discuss the theoretical and practical implications for providing effective psychosocial support for women with breast cancer. PMID- 22070451 TI - Comparison of recipient outcomes following transplant from local versus imported pancreas donors. AB - The shortage of deceased donor organs for solid organ transplantation continues to be an ongoing dilemma. One approach to increase the number of pancreas transplants is to share organs between procurement regions. To assess for the effects of organ importation, we reviewed the outcomes of 1014 patients undergoing deceased donor pancreas transplant at a single center. We performed univariate and multivariate analyses of the association of donor, recipient and surgical characteristics with patient outcomes. Organ importation had no effect on graft or recipient survival for recipients of solitary pancreas transplants. Similarly, there was no effect on technical failure rate, graft survival or long term patient survival for simultaneous kidney-pancreas (SPK) recipients. In contrast, there was a significant and independent increased risk of death in the first year in SPK recipients of imported organs. SPK recipients had longer hospitalizations and increased hospital costs. This increased medical complexity may make these patients more susceptible to short-term complications resulting from the longer preservation times of import transplants. These findings support the continued use of organ sharing to reduce transplant wait times but highlight the importance of strategies to reduce organ preservation times. PMID- 22070452 TI - Nurse-led delivery of specialist supportive care for bipolar disorder: a randomized controlled trial. AB - The aim of the study is (1) to assess the feasibility of delivering nurse-led specialist supportive care as an adjunct to usual care in the clinical setting; (2) to examine the relationship between the delivery of specialist supportive care and improved self-efficacy and functioning and reduced depressive symptoms. A randomized controlled trial of the clinical effectiveness of specialist supportive care as an adjunct to usual care was conducted in community mental health services at one site. Participants were randomized to either usual care or usual care and the adjunctive intervention. Self-report measures of depression, general functioning and self-efficacy were completed by participants in both groups at baseline and 9 months. The intervention was delivered parallel to usual treatment arrangements. While recruitment numbers were sufficient, a low rate of engagement meant we were unable to show significant differences in depressive symptoms or self-efficacy between the usual care group and the specialist supportive care plus usual care group. This study demonstrated that it was difficult to engage patients with bipolar disorder in specialist supportive care when they were currently in a mood episode and under the care of community mental health services. PMID- 22070453 TI - SCORAD 75: a new metric for assessing treatment outcomes in atopic dermatitis. AB - OBJECTIVE: The scoring atopic dermatitis (SCORAD) is a well-established severity scoring tool for atopic dermatitis (AD). Dead Sea climatotherapy (DSC) is a natural selective balneo-phototherapy utilized for many years to treat severe AD. The study's goal was to evaluate the impact of DSC on AD patients through assessment of SCORAD scores and to identify parameters associated with greater improvement. METHODS: The files of 78 European patients (37 male patients and 41 female patients, mean age 37.8 years) with AD undergoing DSC were included in this retrospective study. Three sub-groups were delineated based on disease severity (as determined using the SCORAD). Demographic and clinical parameters as well as treatment characteristics--maximal and cumulative sun exposure doses- were recorded. SCORAD values were again recorded for assessment of treatment response. SCORAD 75 was defined as >=75% decrease in SCORAD values following therapy. Statistical analysis including logistic regression models was used in multivariable analysis. RESULTS: After an average of 30 days of treatment, mean SCORAD values dropped from 50.5 to 11 (76.7%, P<0.001). 64.1% of all patients, regardless of sub-group, reached SCORAD 75, whereas 78.9% of patients with severe disease achieved this result. In a multivariate logistic regression, factors associated with achieving SCORAD 75 were maximal sun exposure, family history of AD and age at disease onset (P=0.002, P=0.009 and P=0.040 respectively). CONCLUSION: Dead Sea climatotherapy is a particularly effective treatment method for the sub-population of adults with severe AD. The SCORAD 75 can be useful for defining sub-populations in which treatment is more likely to be successful. PMID- 22070455 TI - Care as a matter of courage: vulnerability, suffering and ethical formation in nursing care. AB - The aim of the study was to explore nurses' experience of how their own vulnerability and suffering influence their ethical formation and their capacity to provide professional care when they are confronted with the patient's vulnerability and suffering. Care is shaped in the meeting between human beings. Professional care is informed by the patient's appeal for help as it is expressed in the meeting. Ethical formation is understood as a personal ethical and existential process, resulting in the capacity to provide professional care. A nurse must have the sense of being a complete human being with own personal attributes and sensitivity in order to be able to relate to other people. The study is based on qualitative interviews with 23 experienced nurses from Sweden, Finland and Denmark. The analyses and interpretation were carried out in line with Steinar Kvale's three levels of interpretation. The study clarifies that ethical formation is a union of the nurse's personal attributes and professional qualifications and that ethical formation is developed over time. Moreover, it also demonstrates that the nurse's personal and professional life experiences of vulnerability and suffering influence ethical formation. Vulnerability and suffering have proven to be sensitive issues for nurses, like a sore point that either serve as an eye-opener or cause the development of blind spots. Furthermore, vulnerability, suffering and the sore points are seen to shape the nurse's courage in relation to care. Courage appears to be a significant unifying phenomenon that manifests itself as the courage to help patients face their own vulnerability and suffering, to bear witness to patients' vulnerability and suffering and to have faith in oneself in arguing for and providing professional care. Courage thus seems to play a significant role in nurses' ability to engage in care. Nurses' own vulnerability, suffering and sore points seem to shape their courage. PMID- 22070454 TI - Loss-of-function mutations affecting a specific Glycine max R2R3 MYB transcription factor result in brown hilum and brown seed coats. AB - BACKGROUND: Although modern soybean cultivars feature yellow seed coats, with the only color variation found at the hila, the ancestral condition is black seed coats. Both seed coat and hila coloration are due to the presence of phenylpropanoid pathway derivatives, principally anthocyanins. The genetics of soybean seed coat and hilum coloration were first investigated during the resurgence of genetics during the 1920s, following the rediscovery of Mendel's work. Despite the inclusion of this phenotypic marker into the extensive genetic maps developed for soybean over the last twenty years, the genetic basis behind the phenomenon of brown seed coats (the R locus) has remained undetermined until now. RESULTS: In order to identify the gene responsible for the r gene effect (brown hilum or seed coat color), we utilized bulk segregant analysis and identified recombinant lines derived from a population segregating for two phenotypically distinct alleles of the R locus. Fine mapping was accelerated through use of a novel, bioinformatically determined set of Simple Sequence Repeat (SSR) markers which allowed us to delimit the genomic region containing the r gene to less than 200 kbp, despite the use of a mapping population of only 100 F6 lines. Candidate gene analysis identified a loss of function mutation affecting a seed coat-specific expressed R2R3 MYB transcription factor gene (Glyma09g36990) as a strong candidate for the brown hilum phenotype. We observed a near perfect correlation between the mRNA expression levels of the functional R gene candidate and an UDP-glucose:flavonoid 3-O-glucosyltransferase (UF3GT) gene, which is responsible for the final step in anthocyanin biosynthesis. In contrast, when a null allele of Glyma09g36990 is expressed no upregulation of the UF3GT gene was found. CONCLUSIONS: We discovered an allelic series of four loss of function mutations affecting our R locus gene candidate. The presence of any one of these mutations was perfectly correlated with the brown seed coat/hilum phenotype in a broadly distributed survey of soybean cultivars, barring the presence of the epistatic dominant I allele or gray pubescence, both of which can mask the effect of the r allele, resulting in yellow or buff hila. These findings strongly suggest that loss of function for one particular seed coat-expressed R2R3 MYB gene is responsible for the brown seed coat/hilum phenotype in soybean. PMID- 22070456 TI - Late-onset bipolar illness: the geriatric bipolar type VI. AB - In parallel to considerable progress in understanding and treatment of bipolarity and despite growing interest in old age psychiatry, late-onset bipolar illness (LOBI) has remained relatively understudied so far, probably in reason of its complexity. To update available data, a systematic review was conducted, focusing on the main issues addressed in literature in regard to this topic. In addition to data on epidemiology, clinical features and treatment, five main issues could be identified: LOBI as secondary disorder, LOBI as expression of a lower vulnerability to the disease, LOBI as subform of pseudodementia, LOBI as risk factor for developing dementia, and LOBI as bipolar type VI (bipolarity in the context of dementia like processes). Levels of available evidence were found to vary according to the addressed issue. Although the concept of bipolar type VI could be criticized for subsuming under one single heading all the four other issues, this concept may be of pragmatic value in helping clinicians to orientate both diagnosis process and treatment decisions. Among others, the question as to whether some forms of bipolar type VI could constitute a special risk factor for developing dementia deserves further investigation. More studies are also needed to better disentangle the effects of age at onset from those of age itself. PMID- 22070457 TI - CD47-deficient mice have decreased production of intestinal IgA following oral immunization but a maintained capacity to induce oral tolerance. AB - Signal regulatory protein alpha (SIRPalpha/CD172a), expressed by myeloid cells including CD11b(+) dendritic cells, interacts with ubiquitously expressed CD47 to mediate cell-cell signalling and therefore, may be pivotal in the development of tolerance or immunity. We show that in mice deficient in CD47 (CD47(-/-) ) the cellularity in gut-associated lymphoid tissues is reduced by 50%. In addition, the frequency of CD11b(+) CD172a(+) dendritic cells is significantly reduced in the gut and mesenteric lymph nodes, but not in Peyer's patches. Activation of ovalbumin (OVA)-specific CD4(+) T cells in the mesenteric lymph nodes after feeding OVA is reduced in CD47(-/-) mice compared with wild-type however, induction of oral tolerance is maintained. The addition of cholera toxin generated normal serum anti-OVA IgG and IgA titres but resulted in reduced intestinal anti-OVA IgA in CD47(-/-) mice. Replacing the haematopoietic compartment in CD47(-/-) mice with wild-type cells restored neither the cellularity in gut-associated lymphoid tissues nor the capacity to produce intestinal anti-OVA IgA following immunization. This study demonstrates that CD47 signalling is dispensable for oral tolerance induction, whereas the expression of CD47 by non-haematopoietic cells is required for intestinal IgA B-cell responses. This suggests that differential CD4 T cell functions control tolerance and enterotoxin-induced IgA immunity in the gut. PMID- 22070458 TI - Outer retinal oxygen consumption of rat by phosphorescence lifetime imaging. AB - PURPOSE: Since the metabolic function of the retinal tissue is altered due to physiologic changes or disease, measurements of outer retinal oxygen consumption (Q(OR)) may be beneficial in assessment of retinal status. The purpose of this study was to report measurements of Q(OR) in rats using a phosphorescence lifetime imaging technique. METHODS: Phosphorescence lifetime imaging was performed and retinal PO(2) maps were generated in 10 rats under a light-adapted condition. Depth-resolved retinal PO(2) profiles were derived from the PO(2) maps. From the profiles, the maximum outer retina PO(2) (P(max)O(2)) was obtained and Q(OR) was calculated using a one-dimensional oxygen diffusion model. Repeatability, inter-location variability, and inter-subject variability of P(max)O(2) and Q(OR) measurements were established. RESULTS: Intraclass correlation coefficients of repeated measurements of P(max)O(2) and Q(OR) were 0.89 and 0.70, respectively (P < 0.001). Inter-location variability of P(max)O(2) and Q(OR) measurements at superior to inferior contiguous locations on the retina were on average 9 mmHg and 0.22 ml O(2)/100 g-tissue-min, respectively. Mean and standard deviation of P(max)O(2) and Q(OR) measurements averaged over all rats were 60 +/- 16 mmHg and 0.73 +/- 0.28 ml O(2)/100 g-tissue-min, respectively. Inter-subject variability of P(max)O(2) and Q(OR) measurements was on average 2.3 and 1.5 times inter-location variability, respectively. CONCLUSIONS: Measurements of outer retinal oxygen consumption can be made by phosphorescence lifetime imaging and may be of potential value for detecting changes in retinal oxygen metabolic activity due to altered physiological and pathological conditions over multiple locations and time points. PMID- 22070459 TI - Silicon nanowire fabric as a lithium ion battery electrode material. AB - A nonwoven fabric with paperlike qualities composed of silicon nanowires is reported. The nanowires, made by the supercritical-fluid-liquid-solid process, are crystalline, range in diameter from 10 to 50 nm with an average length of >100 MUm, and are coated with a thin chemisorbed polyphenylsilane shell. About 90% of the nanowire fabric volume is void space. Thermal annealing of the nanowire fabric in a reducing environment converts the polyphenylsilane coating to a carbonaceous layer that significantly increases the electrical conductivity of the material. This makes the nanowire fabric useful as a self-supporting, mechanically flexible, high-energy-storage anode material in a lithium ion battery. Anode capacities of more than 800 mA h g(-1) were achieved without the addition of conductive carbon or binder. PMID- 22070460 TI - X-ray spectrometry. PMID- 22070462 TI - Tools for the job: why relying on risk assessment tools is still a risky business. AB - This theoretical review paper examines the applicability of assessment tools, guidelines and protocols in mental health and substance use care on the basis of the construction of such tools and their reliance on aggregate and actuarial methodologies. Evidence-based practice leads clinicians to increasing reliance on tools for assessment of health status, risk and prediction for a range of clinical needs for individual clients. In the longer-term management of people with enduring and chronic mental health and substance misuse problems, clinicians are often dealing with complex and unstable health needs. The tools available, however, are developed on the basis of majority population evidence and on presumptions of similarity and stability over time. This paper provides explanation of the basis for the development of such tools and argues that clinicians need to be able to evaluate the applicability of tools used for their clients and not just evaluate the internal validity of the tools used to make individual and contextual decisions about individual clients. PMID- 22070461 TI - Biological correlates of post-stroke fatigue: a systematic review. AB - Fatigue is a common and disabling consequence of stroke. Its mechanisms are unknown. Neuroanatomical abnormalities (e.g. white matter lesions, brain atrophy), neuroendocrine dysregulation, neurotransmitter changes and inflammation are associated with fatigue in conditions other than stroke. This review sought to identify published studies describing associations between post-stroke fatigue and these biological factors. We searched Medline, EMBASE, CINAHL, PsycINFO and AMED on October 15 and PubMed on 28 December 2010 and included studies in English that recruited at least 10 patients (>18 years old) with stroke, assessed fatigue and reported its relationship with neuroanatomical abnormalities, hypothalamo pituitary-adrenal axis dysregulation, neurotransmitter changes or inflammation. Of 4916 citations from the searches, 17 studies met our inclusion criteria. There was no association between white matter lesions, brain atrophy or pathological type of stroke and fatigue (seven studies, n = 4746). The data on relationship between lesion location and fatigue were inconclusive: four (n = 675) of 13 studies (n = 1613) showed associations between fatigue and infratentorial lesion location (brainstem in particular) or basal ganglia stroke. One study reported C reactive protein levels and found an association with fatigue. No studies reported hypothalamo-pituitary-adrenal axis dysregulation or neurotransmitter changes and fatigue. We could not perform meta-analysis because the studies used different methods of fatigue assessment, examined different populations and had different designs. The biological mechanisms of post-stroke fatigue are uncertain. Further studies are required to determine the relationship between post-stroke fatigue and biological factors. PMID- 22070463 TI - Extensive characterization of Tupaia belangeri neuropeptidome using an integrated mass spectrometric approach. AB - Neuropeptidomics is used to characterize endogenous peptides in the brain of tree shrews (Tupaia belangeri). Tree shrews are small animals similar to rodents in size but close relatives of primates, and are excellent models for brain research. Currently, tree shrews have no complete proteome information available on which direct database search can be allowed for neuropeptide identification. To increase the capability in the identification of neuropeptides in tree shrews, we developed an integrated mass spectrometry (MS)-based approach that combines methods including data-dependent, directed, and targeted liquid chromatography (LC)-Fourier transform (FT)-tandem MS (MS/MS) analysis, database construction, de novo sequencing, precursor protein search, and homology analysis. Using this integrated approach, we identified 107 endogenous peptides that have sequences identical or similar to those from other mammalian species. High accuracy MS and tandem MS information, with BLAST analysis and chromatographic characteristics were used to confirm the sequences of all the identified peptides. Interestingly, further sequence homology analysis demonstrated that tree shrew peptides have a significantly higher degree of homology to equivalent sequences in humans than those in mice or rats, consistent with the close phylogenetic relationship between tree shrews and primates. Our results provide the first extensive characterization of the peptidome in tree shrews, which now permits characterization of their function in nervous and endocrine system. As the approach developed fully used the conservative properties of neuropeptides in evolution and the advantage of high accuracy MS, it can be portable for identification of neuropeptides in other species for which the fully sequenced genomes or proteomes are not available. PMID- 22070464 TI - Hospitalized mental health patients and oral health. AB - The purpose of this review of the literature is to present a contemporary perspective related to the nursing care of hospitalized mental health patients who have risk of developing oral health issues. Mental illness is a major health concern worldwide. Compounding this health issue, mental health patients/clients demonstrate avoidant behaviours related to oral health, and the symptoms of mental illness can be a compounding factor. Oral health and oral inflammatory disease are the result of lifestyle and behaviour and mental disorders affect both lifestyle and behaviour. The search used the search terms oral health AND nursing AND mental illness AND Published Date 2005 to 2010. For those who experience mental illness oral health assessment is not routinely practised by clinicians. The importance of special attention to dental problems for people with mental disorders has also been stressed by researchers since the lifespan of people with serious mental disorders is shortened compared to the general population. Oral health care is an important part of treatment. Routine oral care for hospitalized patients is imperative, and this is usually the responsibility of nurses without sufficient knowledge in oral care or comprehensive protocols to follow. PMID- 22070465 TI - Determination of the specific surface area of snow using ozonation of 1,1 diphenylethylene. AB - We measured the kinetics of ozonation reaction of 1,1-diphenylethylene (DPE) in artificial snow, produced by shock freezing of DPE aqueous solutions sprayed into liquid nitrogen. It was demonstrated that most of the reactant molecules are in direct (productive) contact with gaseous ozone, thus the technique produces snow with organic molecules largely ejected to the surface of snow grains. The kinetic data were used to evaluate the snow specific surface area (~70 cm(2) g(-1)). This number is a measure of the availability of the molecules on the surface for chemical reaction with gaseous species. The experimental results were consistent with the Langmuir-Hinshelwood type reaction mechanism. DPE represents environmentally relevant compounds such as alkenes which can react with atmospheric ozone, and are relatively abundant in natural snow. For typical atmospheric ozone concentrations in polar areas (20 ppbv), we estimated that half life of DPE on the surface of snow grains is ~5 days at submonolayer coverages and -15 degrees C. PMID- 22070466 TI - Immunological responses of male White Leghorn chicks kept on ochratoxin A (OTA) contaminated feed. AB - This study was designed to evaluate some immunological responses of male White Leghorn (WL) chicks kept on an ochratoxin A (OTA)-contaminated diet. For this purpose, 350 1-day-old male WL chicks were divided into five groups (A-E). Group A was kept as control, while Groups B, C, D, and E were fed OTA-contaminated feed at 0.1, 0.5, 1.0, and 1.5 mg/Kg diet, respectively, for 21 days, and then basal ration for the remaining period. At 14- and 16-days of age, random chicks (n = 10) from each group were used for analyses of phagocytic function of the reticuloendothelial system or for measuring the lymphoproliferative responses to intradermally-administered T-cell mitogen, phytohemagglutinin-P (PHA-P), respectively. At 30-days of age, abdominal macrophages were collected from 15 chicks/group and utilized for determination of their phagocytic potential and for nitrite production. Antibody (Ab) titers (i.e., total antibodies, IgM, and IgG) against sheep red blood cells (SRBC) were determined at 7 and 14 days after a primary (at 7 days of age) and a booster (given 14 days after primary [at 21-days of age]) dose (intravenous) of the antigen. Data from the present study showed that the relative weight of the bursa of Fabricius of chicks fed OTA for 14 and 21 days and the spleen of chicks fed OTA for 21 days were significantly lower than their control counterpart. Phagocytic function of reticuloendothelial system evaluated by carbon clearance, and lymphoproliferative response to PHA-P, of chicks kept on OTA-contaminated diet were significantly lowered. The percentage of abdominal macrophages displaying phagocytosis of SRBC, the number of SRBC/macrophage, and nitrite production were each significantly lower in cells from chicks in the OTA-fed groups. Total Ab (at days 7 and 14 post-booster SRBC injection) and IgG (at day 14 post-primary and day 7 post-booster SRBC injection) titers against SRBC showed significant reductions in the groups fed OTA contaminated diet. The findings of this study are in line with the previous work suggesting the immunosuppressive effect of OTA in male WL chicks regarding functional impairment in some of the components of the immune system. PMID- 22070467 TI - Managing the cellular redox hub in photosynthetic organisms. AB - Light-driven redox chemistry is a powerful source of redox signals that has a decisive input into transcriptional control within the cell nucleus. Like photosynthetic electron transport pathways, the respiratory electron transport chain exerts a profound control over gene function, in order to balance energy (reductant and ATP) supply with demand, while preventing excessive over-reduction or over-oxidation that would be adversely affect metabolism. Photosynthetic and respiratory redox chemistries are not merely housekeeping processes but they exert a controlling influence over every aspect of plant biology, participating in the control of gene transcription and translation, post-translational modifications and the regulation of assimilatory reactions, assimilate partitioning and export. The number of processes influenced by redox controls and signals continues to increase as do the components that are recognized participants in the associated signalling pathways. A step change in our understanding of the overall importance of the cellular redox hub to plant cells has occurred in recent years as the complexity of the management of the cellular redox hub in relation to metabolic triggers and environmental cues has been elucidated. This special issue describes aspects of redox regulation and signalling at the cutting edge of current research in this dynamic and rapidly expanding field. PMID- 22070468 TI - Patient involvement in mental health care: one size does not fit all. AB - BACKGROUND: Involvement of mental health-care patients in the decision-making processes is considered to be an ethical requirement. Health-care systems worldwide are increasingly emphasizing the value of participatory approaches. There is, however, no consensus on the definition of patient involvement. The literature is particularly inconsistent and lacks clarity. OBJECTIVE: The purpose of this article is to clarify the concept of patient involvement in mental health care (MHC), taking into account its multidimensional nature. SEARCH STRATEGY: We searched the literature in online databases from January 1998 until August 2010 using synonyms of 'patient involvement', combined with the terms 'mental health(care)'. DATA SYNTHESIS: Based on 45 different descriptions found in the literature, we constructed a definition of patient involvement and we drew up a model identifying its determinants and outcomes. RESULTS: We propose a comprehensive model of patient involvement to be used in MHC. This model can serve as a guide for policy makers and field workers to shape policies to stimulate involvement. DISCUSSION AND CONCLUSIONS: There are three main problems in the literature concerning patient involvement. First, there is a proliferation of conceptualizations of the topic, leading to conceptual vagueness. Furthermore, there is a lack of quantitative data, and some aspects of involvement remain underexposed, such as the involvement of specific target groups and practical ways to shape the involvement processes. Involvement processes should be tailored to the specific target group and context. PMID- 22070469 TI - Mindfulness-based cognitive therapy for nonremitted patients with bipolar disorder. AB - INTRODUCTION: Bipolar disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, many individuals with bipolar disorder continue to experience substantial residual mood symptoms that often lead to the recurrence of mood episodes. AIMS: This study explored whether a new mindfulness-based cognitive therapy (MBCT) for bipolar disorder would increase mindfulness, reduce residual mood symptoms, and increase emotion-regulation abilities, psychological well-being, positive affect, and psychosocial functioning. Following a baseline clinical assessment, 12 individuals with DSM-IV bipolar disorder were treated with 12 group sessions of MBCT. RESULTS: At the end of treatment, as well as at the 3 months follow-up, participants showed increased mindfulness, lower residual depressive mood symptoms, less attentional difficulties, and increased emotion-regulation abilities, psychological well-being, positive affect, and psychosocial functioning. CONCLUSIONS: These findings suggest that treating residual mood symptoms with MBCT may be another avenue to improving mood, emotion regulation, well-being, and functioning in individuals with bipolar disorder. PMID- 22070471 TI - Laparoscopic management of large ovarian tumors: clinical tips for overcoming common concerns. AB - AIM: This study was performed to assess the feasibility and efficacy of laparoscopic management for patients with large ovarian tumors. MATERIAL AND METHODS: A retrospective analysis was performed of the medical records of 52 women who underwent laparoscopic surgery for large ovarian tumors whose maximum diameter was >=15cm and a low possibility of malignancy. RESULTS: The median age of patients was 35years (range 18-84), median body mass index was 22.4kg/m(2) (range 12.4-31.5) and 18 patients had previous operative history. The median tumor diameter was 17cm (range 15-40). There were no conversions to laparotomy and perioperative complications. The median operating time, estimated blood loss, and hospital stay were 80min (range 25-225), 100mL (range 50-500) and 3days (range 2-14), respectively. The operative procedures performed were salpingo oophorectomy (n=26), ovarian cystectomy (n=16), laparoscopically assisted vaginal hysterectomy with unilateral or bilateral salpingo-oophorectomy (n=9), and laparoscopically assisted staging surgery (n=1). The histopathological results were mucinous cystadenoma (n=25), mature cystic teratoma (n=9), serous cystadenoma (n=6), endometrioma (n=5), mucinous borderline tumor (n=4), follicular cyst (n=2), and clear cell carcinoma (n=1). CONCLUSION: Laparoscopic management of large ovarian tumors is feasible and efficient with appropriate patient selection and experience of surgeons. PMID- 22070470 TI - Association between carotid area calcifications and periodontal risk: a cross sectional study of panoramic radiographic findings. AB - BACKGROUND: The aim was to investigate the extent to which it is possible to diagnose suspected carotid calcification from dental panoramic radiography (PR) and to establish an association to periodontal risk. METHODS: 824 PRs from one dental practice were investigated. Parameters considered were gender, age, bone loss - age index, tooth loss, periodontal risk and suspected carotid calcification (left, right, both sides). Periodontal risk was classified: low risk (under 4 missing teeth, bone loss - age index under 0.5), moderate risk (5 to 8 missing teeth and/or bone loss - age index 0.5 to 1.0) and high risk (more than 9 missing teeth and or bone loss - age index greater than 1.0). RESULTS: Of 824 patients, 349 were male (42.4%) and 475 female (57.6%); the mean age was 48.32 +/- 16.52 years. In 9.0% (n = 74) of PRs, suspected carotid calcification was diagnosed (right: 5.5%, left: 2.3%, both sides: 1.2%). The mean tooth loss was 4.16 +/- 5.39 teeth. In the case of 282 patients (34.2%), there was a low, in 335 patients (40.7%) a moderate, and in 207 patients (25.1%) a high periodontal risk. There was a significant correlation found between number of cases of suspected carotid calcification and periodontal risk, tooth loss and age (p = 0.0001). However, only age showed a significant association (OR: 4.9; CI: 2.4 9.8; p < 0.0001) in contrast to periodontal risk (OR 1.4; CI: 0.9-2.4). CONCLUSION: PR can provides indication of carotid calcification as a secondary (chance) finding. In addition, periodontal risk may be correlated with positive findings of carotid calcification. PMID- 22070472 TI - Perioperative opiate requirements in children with previous opiate infusion. AB - BACKGROUND: Critically ill children often require continuous opiate infusions. Tolerance may develop requiring a weaning strategy to prevent withdrawal symptoms. These children may also require subsequent surgical procedures. This is the first study to investigate whether previously opiate-tolerant patients require higher doses of opiates for adequate pain management perioperatively. METHODS: A retrospective study was conducted at a tertiary children's hospital to investigate whether children previously exposed to continuous opiates for 10 or more days with subsequent weaning from those opiates will have similar or increased perioperative opiate requirements when compared to opioid-naive controls. Study patients included 31 children with previous continuous opiate exposure for 10 or more days followed by weaning and without signs of withdrawal for at least 72 h prior to the surgical procedure. Excluded were patients over 18 years of age, those whose surgical procedures would be unlikely to require perioperative opiates, oncological patients, burn patients, neurologically devastated patients, and patients who received regional anesthesia in addition to perioperative narcotics. The control group consisted of 31 age- and case-matched opiate-naive patients who underwent a surgical procedure during a similar time frame as the study patient. The medication administration record was reviewed for the length of continuous opiate exposure, date of last opiate use prior to a subsequent surgical procedure, and opiate use during the perioperative period. Opiate use was calculated as morphine equivalents per kilogram body weight (MSEQ.kg(-1)). The Wilcoxon rank sum test was used for univariate comparisons between matched pairs, and P-values <0.05 were considered statistically significant. RESULTS: The perioperative opiate requirements in opiate-exposed patients (median, interquartile range: 0.14, 0.08-0.25 MSEQ.kg(-1)) were not significantly different from opiate-naive patients (median, interquartile range 0.10, 0.05-0.2 MSEQ.kg(-1), P = 0.19). Pain scores indicated that patients were generally comfortable in the perioperative period. CONCLUSIONS: The perioperative opiate requirements of pediatric patients who were successfully weaned after prolonged opiate use were similar to opiate-naive patients. A history of prolonged opiate use alone does not necessitate special pain management for future procedures. PMID- 22070473 TI - Inadvertent arterial catheterization complicating femoral venous access for haemodialysis. AB - OBJECTIVE: Large-bore catheters for temporary haemodialysis are often placed via the internal jugular or femoral vein, guided by external landmarks or ultrasound techniques. Inadvertent femoral artery catheterization may occur during attempted placement of the dialysis catheter in the femoral vein. MATERIAL AND METHODS: This investigation was carried out in Skane University Hospital, Malmo, Sweden. Between 2008 and 2011, patients referred for consultation by a vascular specialist owing to inadvertent arterial catheterization after attempted placement of a dialysis catheter in the femoral vein were noted in a logbook and patients with iatrogenic arterial injuries undergoing vascular repair at Malmo Lund Hospitals were identified through the Swedish vascular registry (Swedvasc). RESULTS: The five included patients had a dialysis catheter (11-13.5 Fr) inserted, without ultrasound guidance, into the femoral artery. One patient suffered from circulatory shock. Two cases were managed with external compression, while three cases required surgical repair. Two patients had postoperative wound infection in the groin. CONCLUSIONS: Femoral dialysis catheters should be inserted using ultrasound guidance. Large-bore catheters suspected of being in an inadvertent arterial position should be fixed securely before further diagnostic or interventional considerations. A management algorithm for inadvertently placed catheters in the femoral artery is proposed. PMID- 22070474 TI - Getting moving on patient safety--harnessing electronic data for safer care. PMID- 22070475 TI - Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis. AB - BACKGROUND: Mortality among patients with severe acute alcoholic hepatitis is high, even among those treated with glucocorticoids. We investigated whether combination therapy with glucocorticoids plus N-acetylcysteine would improve survival. METHODS: We randomly assigned 174 patients to receive prednisolone plus N-acetylcysteine (85 patients) or only prednisolone (89 patients). All patients received 4 weeks of prednisolone. The prednisolone-N-acetylcysteine group received intravenous N-acetylcysteine on day 1 (at a dose of 150, 50, and 100 mg per kilogram of body weight in 250, 500, and 1000 ml of 5% glucose solution over a period of 30 minutes, 4 hours, and 16 hours, respectively) and on days 2 through 5 (100 mg per kilogram per day in 1000 ml of 5% glucose solution). The prednisolone-only group received an infusion in 1000 ml of 5% glucose solution per day on days 1 through 5. The primary outcome was 6-month survival. Secondary outcomes included survival at 1 and 3 months, hepatitis complications, adverse events related to N-acetylcysteine use, and changes in bilirubin levels on days 7 and 14. RESULTS: Mortality was not significantly lower in the prednisolone-N acetylcysteine group than in the prednisolone-only group at 6 months (27% vs. 38%, P = 0.07). Mortality was significantly lower at 1 month (8% vs. 24%, P = 0.006) but not at 3 months (22% vs. 34%, P = 0.06). Death due to the hepatorenal syndrome was less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group at 6 months (9% vs. 22%, P = 0.02). In a multivariate analysis, factors associated with 6-month survival were a younger age (P<0.001), a shorter prothrombin time (P<0.001), a lower level of bilirubin at baseline (P<0.001), and a decrease in bilirubin on day 14 (P<0.001). Infections were less frequent in the prednisolone-N-acetylcysteine group than in the prednisolone-only group (P = 0.001); other side effects were similar in the two groups. CONCLUSIONS: Although combination therapy with prednisolone plus N-acetylcysteine increased 1-month survival among patients with severe acute alcoholic hepatitis, 6-month survival, the primary outcome, was not improved. (Funded by Programme Hospitalier de Recherche Clinique; AAH-NAC ClinicalTrials.gov number, NCT00863785 .). PMID- 22070476 TI - Early liver transplantation for severe alcoholic hepatitis. AB - BACKGROUND: A 6-month abstinence from alcohol is usually required before patients with severe alcoholic hepatitis are considered for liver transplantation. Patients whose hepatitis is not responding to medical therapy have a 6-month survival rate of approximately 30%. Since most alcoholic hepatitis deaths occur within 2 months, early liver transplantation is attractive but controversial. METHODS: We selected patients from seven centers for early liver transplantation. The patients had no prior episodes of alcoholic hepatitis and had scores of 0.45 or higher according to the Lille model (which calculates scores ranging from 0 to 1, with a score >= 0.45 indicating nonresponse to medical therapy and an increased risk of death in the absence of transplantation) or rapid worsening of liver function despite medical therapy. Selected patients also had supportive family members, no severe coexisting conditions, and a commitment to alcohol abstinence. Survival was compared between patients who underwent early liver transplantation and matched patients who did not. RESULTS: In all, 26 patients with severe alcoholic hepatitis at high risk of death (median Lille score, 0.88) were selected and placed on the list for a liver transplant within a median of 13 days after nonresponse to medical therapy. Fewer than 2% of patients admitted for an episode of severe alcoholic hepatitis were selected. The centers used 2.9% of available grafts for this indication. The cumulative 6-month survival rate (+/ SE) was higher among patients who received early transplantation than among those who did not (77 +/- 8% vs. 23 +/- 8%, P<0.001). This benefit of early transplantation was maintained through 2 years of follow-up (hazard ratio, 6.08; P = 0.004). Three patients resumed drinking alcohol: one at 720 days, one at 740 days, and one at 1140 days after transplantation. CONCLUSIONS: Early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy. (Funded by Societe Nationale Francaise de Gastroenterologie.). PMID- 22070477 TI - Sudden, unexpected death in epilepsy. PMID- 22070479 TI - Images in clinical medicine: Bryant's and Stabler's signs after a difficult delivery. PMID- 22070478 TI - The human plasma lipidome. PMID- 22070480 TI - Case records of the Massachusetts General Hospital. Case 34-2011: A 75-year-old man with memory loss and partial seizures. PMID- 22070481 TI - Transplantation for alcoholic hepatitis--time to rethink the 6-month "rule". PMID- 22070483 TI - Early or late parenteral nutrition in critically ill adults. PMID- 22070484 TI - Early or late parenteral nutrition in critically ill adults. PMID- 22070485 TI - Early or late parenteral nutrition in critically ill adults. PMID- 22070486 TI - Early or late parenteral nutrition in critically ill adults. PMID- 22070488 TI - Horse versus rabbit antithymocyte globulin in aplastic anemia. PMID- 22070489 TI - Horse versus rabbit antithymocyte globulin in aplastic anemia. PMID- 22070491 TI - Apixaban after acute coronary syndrome. PMID- 22070493 TI - Oxygen sensing, homeostasis, and disease. PMID- 22070494 TI - Oxygen sensing, homeostasis, and disease. PMID- 22070495 TI - Case 23-2011--Legal considerations. PMID- 22070496 TI - Noninvasive prenatal diagnosis of a fetal microdeletion syndrome. PMID- 22070499 TI - Images in clinical medicine: amenorrhea, abdominal pain, and weight gain. PMID- 22070500 TI - Risk of second primary melanoma: how should be long follow-up be? Ratio of observed and expected cases. PMID- 22070501 TI - In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells. AB - Rituximab is a chimeric anti-CD20 monoclonal antibody (mAb) used in B-cell malignancies, various autoimmune disorders and organ transplantation. Although administration of a single dose of rituximab results in full B-cell depletion in peripheral blood, there remains a residual B-cell population in secondary lymphoid organs. These nondepleted B cells might be altered by exposure to rituximab with subsequent immunomodulatory effects. Therefore, we analyzed in vitro the effects of rituximab on proliferation, activation and differentiation of CD19(+) B cells by means of carboxyfluorescein succinimidyl ester (CFSE)-based multiparameter flow cytometry. Rituximab inhibited the proliferation of CD27(-) naive, but not of CD27(+) memory B cells. Interestingly, upon stimulation with anti-CD40 mAb and interleukin-21 in the presence of rituximab there was an enrichment of B cells that underwent only one or two cell divisions and displayed an activated naive phenotype (CD27(-)IgD(+)CD38(-/+)). The potency of prestimulated B cells to induce T-cell proliferation was increased by exposure of the B cells to rituximab. Of note, after stimulation with rituximab-treated B cells, proliferated T cells displayed a more Th2-like phenotype. Overall, these results demonstrate that rituximab can affect human B-cell phenotype and function, resulting in an altered outcome of B-T cell interaction. PMID- 22070502 TI - Late-life depression: systematic assessment of care needs as a basis for treatment. AB - Research shows that most of the variance in depression severity levels in late life can be explained by the unmet psychological needs of patients, more in particular the care needs of patients related with psychological distress. This case report describes the treatment of an 84-year-old patient suffering from depression. Her complaints faded upon the use of nursing interventions that were defined on the basis of a systematic assessment of her care needs with the Camberwell Assessment of Needs for the Elderly. The methodical attention to her needs for care and the interventions carried out led to the patient feeling acknowledged and to a diminished need for care and a better quality of life. Although there is no scientific evidence to date, a systematic assessment of care needs may well be a meaningful addition to the nursing diagnostic process. Moreover, alleviating distress in patients by fulfilling unmet care needs through tailored interventions can be seen as an essential element of an effective multidisciplinary depression treatment process. PMID- 22070503 TI - A qualitative analysis of success stories from Michiana Coordinated School Health Leadership institute participants. AB - BACKGROUND: The purpose of this study was to detect and document common themes among success stories, along with challenges, as related by participants in the Michiana Coordinated School Health Leadership Institute. Four-member teams from 18 Michigan and Indiana school districts participated in semiannual Institute workshops over a 3-year period and were tasked with implementing Coordinated School Health Programs (CSHPs). METHODS: Qualitative methods were used to generate themes from interviews. Data were gathered through a combined survey/interview process related to programmatic successes, evidence of success, and implementation challenges. One participant from 11 of 18 participating school districts completed the survey/interview. RESULTS: Each participant reported at least 1 success that had a positive effect on students and/or staff, many of which were related to the federally mandated wellness policy. With some notable exceptions, success was based on subjective judgments rather than systematically collected data. Unanimous expression of time constraints and being overworked in their current positions constituted major challenges. CONCLUSIONS: Although the Institute required only process evaluation, some participants collected outcome data, a task that is important in validating the benefits of CSHPs. Most districts were not able to hire the recommended coordinator to ensure implementation of health program planning initially developed during the institute. Encouragingly, at the time of data collection many teams were still acting to ensure health programming remained a priority. Nevertheless, without the network of social support provided by the Institute, some respondents struggled to maintain momentum. PMID- 22070504 TI - Associations of physical fitness and academic performance among schoolchildren. AB - BACKGROUND: Public schools provide opportunities for physical activity and fitness surveillance, but are evaluated and funded based on students' academic performance, not their physical fitness. Empirical research evaluating the connections between fitness and academic performance is needed to justify curriculum allocations to physical activity programs. METHODS: Analyses were based on a convenience sample of 254,743 individually matched standardized academic (TAKSTM) and fitness (FITNESSGRAM((r)) ) test records of students, grades 3-11, collected by 13 Texas school districts. We categorized fitness results in quintiles by age and gender and used mixed effects regression models to compare the academic performance of the top and bottom fitness groups for each test. RESULTS: All fitness variables except body mass index (BMI) showed significant, positive associations with academic performance after adjustment for socio-demographic covariates, with standardized mean difference effect sizes ranging from .07 to .34. Cardiovascular fitness showed the largest interquintile difference in TAKS score (32-75 points), followed by curl-ups. Additional adjustment for BMI and curl-ups showed dose-response associations between cardiovascular fitness and academic scores (p < .001 for both genders and outcomes). Analysis of BMI demonstrated limited, nonlinear association with academic performance after socio-demographic and fitness adjustments. CONCLUSIONS: Fitness was strongly and significantly related to academic performance. Cardiovascular fitness showed a dose-response association with academic performance independent of other socio-demographic and fitness variables. The association appears to peak in late middle to early high school. We recommend that policymakers consider physical education (PE) mandates in middle high school, school administrators consider increasing PE time, and PE practitioners emphasize cardiovascular fitness. PMID- 22070505 TI - School administrators' perceptions of factors that influence children's active travel to school. AB - BACKGROUND: Increasing children's active travel to school may be 1 strategy for addressing the growing prevalence of obesity among school age children. Using the School Travel Survey, we examined South Carolina school district leaders' perceptions of factors that influence elementary and middle school students walking to school. METHODS: Frequency distributions and chi-square tests were used to analyze the survey responses; open-ended questions were reviewed qualitatively for recurring topics and themes. RESULTS: School and district leaders (N = 314) most often reported street crossing safety (54.0%) and number of sidewalks (54.0%) as priority factors that should be addressed to increase students' active travel to school, followed by distance to school (46.0%), traffic volume (42.4%), parental attitudes (27.0%), traffic speed (26.7%), neighborhood condition (24.4%), and student attitudes (10.0%). Several respondents expressed concerns about liability issues related to students' active travel to school while others reported that schools are not responsible for students' safety once students leave school grounds. Independent of their comments about liability, respondents were concerned about the safety of students while walking to school. CONCLUSIONS: Those promoting active travel to school may benefit from addressing those factors perceived as most important by school and district leaders, including street crossing safety, number of sidewalks, and by educating school and district leaders about liability and safety issues related to students walking to school. PMID- 22070506 TI - The relationship between media use and psychological and physical assets among third- to fifth-grade girls. AB - BACKGROUND: Media use is associated with an increased risk of chronic disease and reduced quality of life among children. This study examined the relationship between media use during discretionary hours after school and psychological and physical assets among preadolescent girls. METHODS: A cross-sectional analysis was conducted using data from a larger quasi-experimental evaluation of a positive youth development program through sport for third- to fifth-grade girls. Indicators of media use were the number of hours per school day spent watching television and videos and using computers. Psychological assets included global self-esteem, body size satisfaction, and commitment to physical activity; physical assets included physical activity. Nested random effects analysis of variance (ANOVA) models were used to examine the relationship between media use and psychological and physical assets controlling for relevant confounding factors. RESULTS: The analytic sample included 1027 participants; most were >=10 years old, non-White; 27% self-reported >=4 hours of media use on school days. In adjusted results, media use was inversely associated with self-esteem (p = .008) and commitment to physical activity (p < .001). Time spent using media was not associated with body size satisfaction or physical activity in this age group. CONCLUSIONS: Media use was negatively associated with self-esteem and commitment to physical activity. It may be useful for school professionals to encourage after-school programs that offer opportunities for girls to reduce sedentary pursuits and improve important psychological and physical assets. PMID- 22070507 TI - School superintendents' perceptions of schools assisting students in obtaining public health insurance. AB - BACKGROUND: Superintendents' perceptions regarding the effect of health insurance status on academics, the role schools should play in the process of obtaining health insurance, and the benefits/barriers to assisting students in enrolling in health insurance were surveyed. Superintendents' basic knowledge of health insurance, the link between health and learning, and specific school system practices for assisting students were also examined. METHODS: A 4-page questionnaire was sent to a national random sample of public school superintendents using a 4-wave postal mailing. RESULTS: Only 19% of school districts assessed the health insurance status of students. School districts' assistance in helping enroll students in health insurance was assessed using Stages of Change theory; 36% of superintendents' school districts were in the action or maintenance stages. The schools most often made health insurance materials available to parents (53%). The perceived benefits identified by more than 80% of superintendents were to keep students healthier, reduce the number of students with untreated health problems, reduce school absenteeism, and improvement of students' attention/concentration during school. The 2 most common perceived barriers identified by at least 50% of superintendents were not having enough staff or financial resources. CONCLUSIONS: Most superintendents believed schools should play a role in helping students obtain health insurance, but the specific role was unclear. Three fourths of superintendents indicated overwhelmingly positive beliefs regarding the effects of health insurance status on students' health and academic outcomes. School personnel and public policy makers can use the results to support collaboration in getting students enrolled in health insurance. PMID- 22070508 TI - Examining how neighborhood disadvantage influences trajectories of adolescent violence: a look at social bonding and psychological distress. AB - BACKGROUND: To understand how neighborhoods influence the development of youth violence, we investigated intrapersonal mediators of the relationship between neighborhood disadvantage and youth violence trajectories between ages 11 and 18. The hypothesized mediators included indicators of social bonding (belief in conventional values, involvement in school activities, religious engagement, and commitment to traditional goals) and psychological distress. METHODS: The sample (N = 5118) was 50% female and 52% Caucasian. Data from a 5-wave panel study spanning ages 11 to 18 were analyzed using sex-stratified multilevel growth curves. RESULTS: Neighborhood disadvantage was associated with higher levels of violence perpetrated by girls, lower belief in conventional values for both girls and boys, less commitment to traditional goals by girls, and higher levels of psychological distress reported by girls. Sobel tests identified 3 significant mediators of the effects of neighborhood disadvantage on girls' violence trajectories: belief in conventional values, commitment to traditional goals, and psychological distress. The only significant mediator of the relationship between neighborhood disadvantage and boys' violence trajectories was belief in conventional values. The effects of neighborhood disadvantage on violence trajectories were not fully mediated; in fact, results suggested that suppression effects, or inconsistent mediation, may exist. CONCLUSIONS: The results emphasize the importance of both contextual and intrapersonal attributes in understanding the development of violence among school-aged youth. Early school-based and community-level prevention initiatives that promote social bonding and address mental health needs may help reduce the impact of youth violence, particularly for girls. PMID- 22070510 TI - The snowball survey and peer education posters: methods of teaching social norms. PMID- 22070509 TI - Utilizing the school health index to build collaboration between a university and an urban school district. AB - BACKGROUND: Insufficient attention has been paid to the process of conducting the Centers for Disease Control and Prevention's School Health Index (SHI) to promote collaboration between universities and urban school districts when developing adolescent health promotion initiatives. This article provides an overview of the real-world contextual challenges and opportunities this type of collaboration can pose. METHODS: The SHI and selected collaboration principles were used to facilitate partnership and increase stakeholder buy-in, which led to developing and implementing an 8-year health promotion campaign. RESULTS: The focus on planning brought together key stakeholders to allow for health promotion programming to take place, despite the competing demands on the schools. The SHI allowed for input from stakeholders to develop campaign activities and inform school- and district-wide policy. Universities and school districts desiring to develop and implement school-based, adolescent health promotion programs should (1) identify the hierarchical structure of the school district, (2) establish credibility for the program and the university staff, (3) emphasize the benefits to all partners, (4) maintain a cooperative partnership with teachers and administrators, (5) appreciate the need for planning, and (6) provide as many resources as possible to aid an already overburdened school system. CONCLUSIONS: Promoting healthy behaviors among students is an important part of the fundamental mission of schools. The significance of collaboration using the SHI, with direct input from students, teachers, administrators, and university partners, is critical in the development of institutional support for implementation of adolescent health promotion initiatives. PMID- 22070511 TI - Improving relationships: serving up a slice of Enemy Pie. PMID- 22070512 TI - Ilaprazole for the treatment of duodenal ulcer: a randomized, double-blind and controlled phase III trial. AB - OBJECTIVE: The new proton pump inhibitor (PPI), ilaprazole performed better at the dose of 10 mg/d relative to 5 or 20 mg/d in a previous phase II trial. A larger phase III trial was carried out to confirm the efficacy and safety of ilaprazole (10 mg/d) compared with omeprazole (20 mg/d) and provide some characteristics of the relationship between ilaprazole metabolism and CYP2C19 for later studies. RESEARCH DESIGN AND METHODS: Patients with at least one endoscopically diagnosed active duodenal ulcer (DU) were enrolled in a multicenter, randomized, double-blind, positive controlled trial and then assigned randomly to the ilaprazole group (10 mg/d) or the omeprazole group (20 mg/d) with a sample allocation ratio 2:1. The course of treatment was 4 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT00952978. MAIN OUTCOME MEASURES: The primary endpoint was endoscopically diagnosed ulcer healing rate at week 4. Symptom relief was evaluated as a secondary endpoint by graded scores. Safety and tolerability were evaluated on basis of clinical assessments. In addition, blood samples were collected at baseline for CYP2C19 genotypes identification. RESULTS: Efficacy analyses were based on 494 patients. At week 4, the ulcer healing rates were 93.0% in ilaprazole group and 90.8% in omeprazole group (rate difference: 2.2%; 95% confidence interval: -2.8% to 7.2%). No obvious variation of healing rate on different CYP2C19 genotypes was found in ilaprazole group. The majority of patients (>80%) became asymptomatic after treatment. Incidences of adverse drug reactions were similar between ilaprazole group and omeprazole group (8.5% vs. 11.5%). CONCLUSIONS: Ilaprazole (10 mg/d) is as effective as omeprazole (20 mg/d) in the treatment of DU with similar side effects. The efficacy of ilaprazole is not affected by CYP2C19 polymorphisms. PMID- 22070514 TI - Safety and effectiveness of azithromycin in the treatment of respiratory infections in children. AB - OBJECTIVES: To describe clinical effectiveness of azithromycin in the management of respiratory tract infections in children up to 12 years of age; to examine duration of symptoms after commencement of therapy and to mark adverse events possibly caused by treatment with azithromycin. METHODS: The overall ITT population included 156 children (65 with acute pharyngitis/tonsillitis (AP), 32 with acute otitis media (AOM), and 59 with lower respiratory tract infections (LRTI)). Clinical effectiveness was based on results of improvement and cure after 3 day's treatment with azithromycin, calculating the clinical score for each diagnosis before treatment, at the 4th day (end of the therapy) and at the 12th or 28th day (end of the study). To better estimate patients' (parents') satisfaction with treatment, a diary was provided for each child and parents recorded the days when a child felt relief of symptoms. RESULTS: In this study azithromycin led to relief of symptoms after 3 days in 89.1% of patients. Antibiotics had been prescribed within 1 year prior to inclusion in 74.4% of patients and 29.5% had previously been treated with macrolides. Clinical effectiveness in the intention-to-treat (ITT) population was 94.8% and there were 5.2% failures. Overall, 18 (11.5%) patients reported 25 adverse events (AEs) and nine AEs were characterized as possibly, probably or definitely related to azithromycin. The most common adverse events were diarrhea in nine (5.8%) cases, vomiting in six (3.8%) and abdominal pain reported in four (2.6 %) patients. CONCLUSION: Results of this study show that azithromycin in the treatment of children with respiratory tract infections has high clinical effectiveness and a small number of adverse events. However, major limitations of the study are its design as a non-comparative, observational, postmarketing study and that the etiology of infections was not confirmed. Despite this, it can be concluded that azithromycin is a reliable antibiotic treatment for children's respiratory tract infections, giving fast resolution of symptoms with few adverse events in patients with presumed bacterial infections. PMID- 22070515 TI - Is there an association between subjective and objective measures of cognitive function in patients with affective disorders? AB - BACKGROUND: Patients with affective disorders experience cognitive dysfunction in addition to their affective symptoms. The relationship between subjectively experienced and objectively measured cognitive function is controversial with several studies reporting no correlation between subjective and objective deficits. AIMS: To investigate whether there is a correlation between subjectively reported and objectively measured cognitive function in patients with affective disorders, and whether subjective complaints predict objectively measured dysfunction. METHODS: The study included 45 participants; 15 with bipolar disorder (BD), 15 with unipolar disorder (UD) and 15 healthy individuals. Participants' subjectively experienced cognitive function and objective cognitive function were assessed with the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) and the Screen for Cognitive Impairment in Psychiatry (SCIP), respectively. Patients were rated for affective symptoms with Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). RESULTS: Patients demonstrated subjective and objective cognitive dysfunction relative to controls (P-values <= 0.01) but there were no differences between patient groups (P > 0.1). We found no correlation between subjectively experienced and objectively measured cognitive dysfunction in BD (P = 0.7), and a non-significant trend towards a correlation in UD (P = 0.06), which disappeared when controlling for gender (P = 0.1). CONCLUSION: Our results suggest that it is not necessarily patients who have cognitive complaints that are most impaired. If confirmed in a larger sample, our findings suggest that neuropsychological assessment is warranted to elucidate the potential role of cognitive dysfunction in patients' everyday lives and to inform treatment strategies targeting these difficulties. PMID- 22070513 TI - Evaluation of clinical use and effectiveness of darbepoetin alfa in cancer patients with chemotherapy-induced anemia. AB - PURPOSE: To investigate the patterns of use of darbepoetin alfa in Spanish centers, and to evaluate its effectiveness in the treatment of chemotherapy induced anemia under clinical practice conditions. METHODS: This was an observational, retrospective, multicenter study in adult patients with non myeloid malignancies who initiated chemotherapy and darbepoetin alfa. Data was collected for up to 16 weeks or until treatment discontinuation. RESULTS: A total of 685 patients (72.7% with solid tumors and 27.3% with hematologic malignancies) were included in the study. Median age was 64.7 years (range 18.5-88.9 years), 50.7% were women, 82.4% had ECOG status 0-1 and 80.5% had stage III/IV cancer. At darbepoetin initiation, mean hemoglobin (Hb) was 100 g/L (SD 10), with 11.0% and 23.1% of patients below 90 g/L in solid and hematologic malignancies, respectively. A decrease in transfusion requirements was observed between weeks 5 16 with respect to weeks 0-16 (13.3% [95% CI: 10.7 to 15.9] versus 19.0% [95% CI: 16.0 to 22.0]). Hb levels were significantly increased during the treatment (mean change of 10.4 g/L for solid tumors [p < 0.001], and 16.6 g/L for hematologic malignancies [p < 0.001]). The percentage of patients with baseline Hb level <110 g/L who achieved an Hb level >=110 g/L during the study was 66.5% (95% CI: 62.5% to 70.5%). Six serious adverse reactions were considered related to darbepoetin alfa (thromboembolic events, 1.0%). CONCLUSIONS: With the limitation of a retrospective design, our results suggest that darbepoetin alfa is a well tolerated treatment that increases hemoglobin levels and reduces the need for transfusion in cancer patients receiving chemotherapy in clinical practice. PMID- 22070516 TI - 15N-labeled brain enables quantification of proteome and phosphoproteome in cultured primary neurons. AB - Terminally differentiated primary cells represent a valuable in vitro model to study signaling events associated within a specific tissue. Quantitative proteomic methods using metabolic labeling in primary cells encounter labeling efficiency issues hindering the use of these cells. Here we developed a method to quantify the proteome and phosphoproteome of cultured neurons using (15)N-labeled brain tissue as an internal standard and applied this method to determine how an inhibitor of an excitatory neural transmitter receptor, phencyclidine (PCP), affects the global phosphoproteome of cortical neurons. We identified over 10,000 phosphopeptides and made accurate quantitative measurements of the neuronal phosphoproteome after neuronal inhibition. We show that short PCP treatments lead to changes in phosphorylation for 7% of neuronal phosphopeptides and that prolonged PCP treatment alters the total levels of several proteins essential for synaptic transmission and plasticity and leads to a massive reduction in the synaptic strength of inhibitory synapses. The results provide valuable insights into the dynamics of molecular networks implicated in PCP-mediated NMDA receptor inhibition and sensorimotor deficits. PMID- 22070517 TI - Possible involvement of monoaminergic neurotransmission in antidepressant-like activity of Emblica officinalis fruits in mice. AB - AIMS: In this study, antidepressant-like activity of Emblica offcinalis Gaertn. fruits (Family: Euphorbiaceae) was evaluated in Swiss young male albino mice employing tail suspension test and forced swim test. METHODS: Aqueous extract (200 and 400 mg/kg) of the fruits was administered orally for 14 successive days to mice. On day 14, 60 min after extract administration, animals were subjected to tail suspension test and forced swim test. RESULTS: The extract significantly decreased immobility period in both tail suspension test and forced swim test, indicating significant antidepressant-like activity. The lower dose (200 mg/kg) of the extract showed better antidepressant-like action. The efficacy of the extract was found to be comparable to fluoxetine (20 mg/kg), imipramine (15 mg/kg), and phenelzine (20 mg/kg). The extract did not show any significant effect on locomotor activity of the mice. Prazosin (alpha(1) -adrenoceptor antagonist), sulpiride (selective D(2) -receptor antagonist), baclofen (GABA(B) agonist), and p-CPA (tryptophan hydroxylase inhibitor) significantly attenuated the extract-induced antidepressant-like effect. The extract also significantly decreased brain MAO-A levels. DISCUSSION: The aqueous extract might produce antidepressant-like effect by interaction with alpha(1)-adrenoceptors, dopamine D(2)- receptors, serotonergic, and GABA(B) receptors. In this study, aqueous extract was found to contain 2.94% of ascorbic acid. So ascorbic acid and other constituents like flavanoids, tannoid principles, and polyphenolic substances present in the aqueous extract of E. officinalis might be responsible for its antidepressant-like activity. CONCLUSIONS: Thus, aqueous extract of E. officinalis showed antidepressant-like activity probably by inhibiting MAO-A and GABA; and also due to its antioxidant activity. PMID- 22070519 TI - Irish psychiatric nurses' self-reported barriers, facilitators and skills for developing evidence-based practice. AB - Evidence-based practice places an emphasis on integration of clinical expertise with available best evidence, patient's clinical information and preferences, and with local health resources. This paper reports the findings of a study that investigated the barriers, facilitators and skills in developing evidence-based practice among psychiatric nurses in Ireland. A postal survey was conducted among a random sample of Irish psychiatric nurses and survey data were collected using the Development of Evidence-Based Practice Questionnaire. Respondents reported that insufficient time to find and read research reports and insufficient resources to change practice were the greatest barriers to the development of evidence-based practice. Practice development coordinators were perceived as the most supportive resource for changing practice. Using the Internet to search for information was the highest-rated skill and using research evidence to change practice was the lowest-rated skill for developing evidence-based practice. Nurses' precursor skills for developing evidence-based practice, such as database searching and information retrieval, may be insufficient in themselves for promoting evidence-based practice if they cannot find evidence relating to their particular field of practice or if they do not have the time, resources and supports to develop their practice in response to evidence. PMID- 22070518 TI - Potentiometric sensors based on fluorous membranes doped with highly selective ionophores for carbonate. AB - Manganese(III) complexes of three fluorophilic salen derivatives were used to prepare ion-selective electrodes (ISEs) with ionophore-doped fluorous sensing membranes. Because of their extremely low polarity and polarizability, fluorous media are not only chemically very inert but also solvate potentially interfering ions poorly, resulting in a much improved discrimination of such ions. Indeed, the new ISEs exhibited selectivities for CO(3)(2-) that exceed those of previously reported ISEs based on nonfluorous membranes by several orders of magnitude. In particular, the interference from chloride and salicylate was reduced by 2 and 6 orders of magnitude, respectively. To achieve this, the selectivities of these ISEs were fine-tuned by addition of noncoordinating hydrophobic ions (i.e., ionic sites) into the sensing membranes. Stability constants of the anion-ionophore complexes were determined from the dependence of the potentiometric selectivities on the charge sign of the ionic sites and the molar ratio of ionic sites and the ionophore. For this purpose, a previously introduced fluorophilic tetraphenylborate and a novel fluorophilic cation with a bis(triphenylphosphoranylidene)ammonium group, (R(f6)(CH(2))(3))(3)PN(+)P(R(f6)(CH(2))(3))(3), were utilized (where R(f6) is C(6)F(13)). The optimum CO(3)(2-) selectivities were found for sensing membranes composed of anionic sites and ionophore in a 1:4 molar ratio, which results in the formation of 2:1 complexes with CO(3)(2-) with stability constants up to 4.1 * 10(15). As predicted by established theory, the site-to-ionophore ratios that provide optimum potentiometric selectivity depend on the stoichiometries of the complexes of both the primary and the interfering ions. However, the ionophores used in this study give examples of charges and stoichiometries previously neither explicitly predicted by theory nor shown by experiment. The exceptional selectivity of fluorous membranes doped with these carbonate ionophores suggests their use not only for potentiometric sensing but also for other types of sensors, such as the selective separation of carbonate from other anions and the sequestration of carbon dioxide. PMID- 22070520 TI - Midregional proadrenomedullin (MR-proADM) is a powerful predictor of early death in AL amyloidosis. AB - BACKGROUND: Cardiac biomarkers play a major role in the identification of patients at risk of early death in AL amyloidosis, and a staging system based on amino-terminal pro-natriuretic peptide type-B (NT-proBNP) and troponins (cTn) is used for prognostic stratification. Adrenomedullin is produced by several tissues including the heart, and portends a poor prognosis in heart diseases. We investigated the ability of midregional proadrenomedullin (MR-proADM) to predict early death in AL amyloidosis. METHODS: One-hundred and thirty consecutive patients with newly-diagnosed AL amyloidosis were prospectively enrolled. The impact on survival of NT-proBNP, cTnI and MR-proADM was evaluated. RESULTS: The concentration of MR-proADM correlated with systolic and diastolic function, but did not reflect the amount of amyloid deposited in the heart. Moreover, MR-proADM was associated with non-cardiac markers of advanced disease. The staging system based on NT-proBNP and cTnI identified high-risk subjects, but could not discriminate good-risk and intermediate-risk patients. Conversely, a staging system based on MR-proADM and cTnI identified 3 groups with significantly different survivals. CONCLUSIONS: Midregional-proADM is a powerful prognostic marker in AL amyloidosis, which may not only reflect cardiac dysfunction but also widespread systemic disease, and can be combined with cTn for detecting patients at risk of early death. PMID- 22070521 TI - Oral status, oral hygiene habits and caries risk factors in home-dwelling elderly dependent on moderate or substantial supportive care for daily living. AB - OBJECTIVES: Elderly people with disabilities have an increased risk of developing oral diseases as compared with the healthy elderly. The aim of this study was to investigate oral hygiene habits, clinical variables related to oral self-care and caries risk in elderly individuals living at home with moderate and substantial needs of home care. METHODS: A random sample of 151 elderly people with moderate needs and 151 with substantial needs of home care were examined. Data concerning general health, social conditions and oral hygiene habits were collected using a questionnaire. Data showing the prevalence of caries, plaque scores and gingival bleeding were obtained through clinical examinations. RESULTS: Elderly subjects with substantial needs of home nursing had more active caries (P < 0.01) and more often gingival bleeding (P < 0.05), as compared with elderly people with moderate needs. Forty-nine per cent of the elderly with moderate needs performed acceptable self-care, as compared with 25% of the individuals with substantial needs. Good self-care was associated with women, low plaque scores, less bleeding and less caries. Factors increasing the risk of having caries were low saliva secretion, high plaque scores and a large number of fillings, while having a dentist and good oral hygiene habits increased the chance of not developing caries. CONCLUSIONS: Good oral hygiene habits were associated with less prevalence of plaque and oral disease in the elderly irrespective of extent of needs of home nursing. However, the elderly with moderate needs more often performed good self-care, indicating that the possibilities of strengthening self care and learning new routines are better when functions are less affected. PMID- 22070522 TI - MicroRNA-1 and microRNA-206 improve differentiation potential of human satellite cells: a novel approach for tissue engineering of skeletal muscle. AB - Innovative strategies based on regenerative medicine, in particular tissue engineering of skeletal muscle, are promising for treatment of patients with skeletal muscle damage. However, the efficiency of satellite cell differentiation in vitro is suboptimal. MicroRNAs are involved in the regulation of cell proliferation and differentiation. We hypothesized that transient overexpression of microRNA-1 or microRNA-206 enhances the differentiation potential of human satellite cells by downregulation quiescent satellite cell regulators, thereby increasing myogenic regulator factors. To investigate this, we isolated and cultured human satellite cells from muscle biopsies. First, through immunofluorescent analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we showed that in satellite cell cultures, low Pax7 expression is related to high MyoD expression on differentiation, and, subsequently, more extensive sarcomere formation, that is, muscle differentiation, was detected. Second, using qRT-PCR, we showed that microRNA-1 and microRNA-206 are robustly induced in differentiating satellite cells. Finally, a gain-of-function approach was used to investigate microRNA-1 and microRNA-206 potential in human satellite cells to improve differentiation potential. As a proof of concept, this was also investigated in a three dimensional bioartificial muscle construct. After transfection with microRNA-1, the number of Pax7 expressing cells decreased compared with the microRNA scrambled control. In differentiated satellite cell cultures transfected with either microRNA-1 or microRNA-206, the number of MyoD expressing cells increased, and alpha-sarcomeric actin and myosin expression increased compared with microRNA scrambled control cultures. In addition, in a three-dimensional bioartificial muscle construct, an increase in MyoD expression occurred. Therefore, we conclude that microRNA-1 and microRNA-206 can improve human satellite cell differentiation. It represents a potential novel approach for tissue engineering of human skeletal muscle for the benefit of patients with facial paralysis. PMID- 22070523 TI - Influencing factors of community mental health nurses caring for people with schizophrenia in Taiwan. AB - The purpose of this study was to explore the influencing factors in the substantive theory of home care for people with schizophrenia in Taiwan. The grounded theory of Strauss and Corbin approach was used. Semi-structured one-to one in-depth interviews were utilized to collect data. Constant comparative analysis continued during the open, axial and selective coding processes until data saturation occurred. Participants were selected using theoretical sampling, and the final sample in this study consisted of a total of 29 community nurses (18 public health nurses and 11 home health nurses) who provided community mental health home-visiting services. The public health nurses and home health nurses both conducted a total of 16 (eight carers and eight clients) home visits. Four categories and 12 subcategories of influencing factors were identified; these factors have both positive and negative effects on nursing roles and the functions of public health nurses in the mental health home-visiting service in Taiwan. The influencing factors identified support the importance of home care services. PMID- 22070524 TI - Evaluation of the nifH gene marker of Methanobrevibacter smithii for the detection of sewage pollution in environmental waters in Southeast Queensland, Australia. AB - This study aimed at evaluating the host-specificity and -sensitivity of the nifH gene marker of Methanobrevibacter smithii by screening 272 fecal and wastewater samples from 11 animal species including humans in Southeast Queensland (SEQ), Australia. In addition, environmental water samples (n = 21) were collected during the dry and wet weather conditions and tested for the presence of the nifH marker along with other sewage-associated markers, namely, enterococci surface protein (esp) found in Enterococci faecium, Bacteroides HF183, adenoviruses (AVs), and polyomaviruses (PVs). The overall host-specificity of the nifH marker to differentiate between human and animal feces was 0.96 (maximum value of 1), while the overall sensitivity of this marker in human sourced feces and wastewater was 0.81 (maximum value of 1). Among the 21 environmental water samples tested, 2 (10%), 3 (14%), 12 (57%), 6 (29%), and 6 (29%) were positive for the nifH, esp, HF183, AVs and PVs markers, respectively. The prevalence of the nifH marker in environmental water samples, however, was low compared to other markers, suggesting that the use of this marker alone may not be sensitive enough to detect fecal pollution in environmental waters. The nifH marker, however, appears to be sewage-specific in SEQ, Australia, and therefore, it is recommended that this marker should be used as an additional marker in combination with the HF183 or viral markers such as AVs or PVs for accurate and sensitive detection of fecal pollution in SEQ waterways. PMID- 22070525 TI - Minimizing pharmacodynamic interactions of high doses of lacosamide. AB - OBJECTIVES: To determine whether pharmacodynamic interactions between high doses of lacosamide (400-800 mg/day) and concomitant sodium channel antiepilepsy drugs (AEDs) can be minimized in patients with drug-resistant partial-onset seizures. MATERIALS AND METHODS: Patients were rapidly initiated with high-dose lacosamide (100 mg/week; increases to 400 to 800 mg/day), while simultaneously tapering concomitant sodium channel AEDs. Seizure frequency and side effects were evaluated at six time points: baseline, titration, 3, 6, 9 and 12 months. RESULTS: Twenty-three patients had a baseline median of 4 seizures/month with persisting partial-onset seizures, despite previous treatment with an average of 6.8 AEDs. Mean decreases in monthly seizure frequency were as follows: 3 months 49.9% (P = 0.011), 6 months 55.4% (P = 0.010), 9 months 60.8% (P = 0.002) and 12 months 58.2% (P = 0.011). Most adverse events were mild CNS-related symptoms and occurred transiently only during titration - there was no significant relationship (chi(2) < 1.5, P > 0.1) between lacosamide dose and the presence of side effects at 3, 6, 9 or 12 months. CONCLUSIONS: Drug-resistant patients rapidly titrated to high doses of lacosamide with simultaneous tapering of traditional sodium channel AEDs had marked reduction in CNS-related adverse events compared with patients treated in three previous pivotal trials that used fixed doses of concomitant AEDs. PMID- 22070526 TI - In vitro tests for aerosol deposition. I: Scaling a physical model of the upper airways to predict drug deposition variation in normal humans. AB - BACKGROUND: In vitro-in vivo correlations (IVIVCs) are needed to relate in vitro test results for deposition to mean data from clinical trials, as well as the extremes in a population. Because drug deposition variations are related to differences in airway dimensions and inhalation profiles, this article describes the development and validation of models and methods to predict in vivo results. METHODS: Three physical models of the upper airways were designed as small, medium, and large versions to represent 95% of the normal adult human population. The physical dimensions were validated by reference to anatomy literature. The models were constructed by rapid prototyping, housed in an artificial thorax, and used for in vitro testing of drug deposition from 200 MUg Budelin Novolizers using a breath simulator to mimic the inhalation profiles used in the clinic. In vitro results were compared to those reported in vivo. RESULTS: The "average" model was scaled to produce "small" and "large" versions by multiplying linear dimensions by 0.748 or 1.165, respectively, based on reports of the mean and standard deviation of airway volume across a normal adult population. In vitro deposition variation under fixed test conditions was small. Testing in the model triplet however, using air flow rate versus time profiles based on the mean and the extremes reported in the clinic, produced results for total lung deposition (TLD) in vitro consistent with the complete range of drug deposition results reported in vivo. The effects of variables such as flow rate in vitro were also predictive of in vivo deposition. CONCLUSIONS: A new in vitro test method is described to predict the median and range of aerosol drug deposition seen in vivo. The method produced an IVIVC that was consistent with 1:1 predictions of total lung deposition from a marketed powder inhaler in trained normal adults. PMID- 22070527 TI - The pharmacokinetics of inhaled morphine delivered by an ultrasonic nebulizer in ventilated dogs. AB - BACKGROUND: To investigate the pharmacokinetics of single dose morphine inhaled by modified ultrasonic nebulizer versus intravenous administered in ventilated dogs. METHODS: Six healthy dogs were randomly assigned to receive nebulized or intravenous morphine and crossed over to the alternative medication 1 week after. Morphine was nebulized by modified ultrasonic nebulizer (YuYue 402A, Jiangsu, China). Arterial blood was sampled every minute during the 10 min of administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, 240, and 360 min after the administration for the determination of morphine concentration by RP-HPLC. RESULTS: The main pharmacokinetic parameters of morphine by inhaled and intravenous administration were: MRT 59+/-14 min versus 19+/-4 min, T(1/2) 21.9+/-5.1 min versus 3.3+/-1.0 min, T(max) 23.0+/-2.7 min versus 8.8+/-2.4 min, C(max) 0.245+/-0.09 mg.L-1 versus 1.09+/-0.32 mg.L-1, AUC(0-infinity) 9.7+/-1.1 mg.min.L-1 versus 15.2+/-7.2 mg.min.L-1, CL 0.069+/-0.019 L.min-1.kg-1 versus 0.063+/-0.028 L.min-1.kg-1, and the absolute bioavailability of inhaled morphine was 35.5+/-10%. There were no significant differences (p<0.05) between inhaled and intravenous morphine in AUC and CL. As expected, the T(1/2) and MRT of inhaled morphine were significantly greater than those of intravenous morphine. CONCLUSIONS: Morphine nebulized by ultrasonic nebulizer can be rapidly and extensively absorbed by lungs in ventilated dogs. PMID- 22070528 TI - Small CAB-like proteins prevent formation of singlet oxygen in the damaged photosystem II complex of the cyanobacterium Synechocystis sp. PCC 6803. AB - The cyanobacterial small CAB-like proteins (SCPs) are single-helix membrane proteins mostly associated with the photosystem II (PSII) complex that accumulate under stress conditions. Their function is still ambiguous although they are assumed to regulate chlorophyll (Chl) biosynthesis and/or to protect PSII against oxidative damage. In this study, the effect of SCPs on the PSII-specific light induced damage and generation of singlet oxygen ((1)O(2)) was assessed in the strains of the cyanobacterium Synechocystis sp. PCC 6803 lacking PSI (PSI-less strain) or lacking PSI together with all SCPs (PSI-less/scpABCDE(-) strain). The light-induced oxidative modifications of the PSII D1 protein reflected by a mobility shift of the D1 protein and by generation of a D1-cytochrome b-559 adduct were more pronounced in the PSI-less/scpABCDE(-) strain. This increased protein oxidation correlated with a faster formation of (1)O(2) as detected by the green fluorescence of Singlet Oxygen Sensor Green assessed by a laser confocal scanning microscopy and by electron paramagnetic resonance spin-trapping technique using 2, 2, 6, 6-tetramethyl-4-piperidone (TEMPD) as a spin trap. In contrast, the formation of hydroxyl radicals was similar in both strains. Our results show that SCPs prevent (1)O(2) formation during PSII damage, most probably by the binding of free Chl released from the damaged PSII complexes. PMID- 22070529 TI - What motivates Australian health service users with chronic illness to engage in self-management behaviour? AB - CONTEXT: Health policy in Australia emphasizes the role of health service users (HSU) in managing their own care but does not include mechanisms to assist HSUs to do so. OBJECTIVE: To describe motivation towards or away from self-management in a diverse group of older Australians with diabetes, chronic heart failure (CHF) or chronic obstructive pulmonary disease (COPD) and suggest policy interventions to increase patient motivation to manage effectively. DESIGN: Content and thematic analyses of in-depth semi-structured interviews. Participants were asked to describe their experience of having chronic illness, including experiences with health professionals and health services. Secondary analysis was undertaken to expose descriptions of self-management behaviours and their corresponding motivational factors. PARTICIPANTS: Health service users with diabetes, COPD and/or CHF (N=52). RESULTS: Participant descriptions exposed internal and external sources of motivation. Internal motivation was most often framed positively in terms of the desire to optimize health, independence and wellness and negatively in terms of avoiding the loss of those attributes. External motivation commonly arose from interactions with family, carers and health professionals. Different motivators appeared to work simultaneously and interactively in individuals, and some motivators seemed to be both positive and negative drivers. CONCLUSION: Successful management of chronic illness requires recognition that the driving forces behind motivation are interconnected. In particular, the significance of family as an external source of motivation suggests a need for increased investment in the knowledge and skill building of family members who contribute to care. PMID- 22070530 TI - Placental alpha-microglobulin-1 rapid immunoassay for detection of premature rupture of membranes. AB - AIM: The aim of the present study was to compare the efficacy of placental alpha microglobulin-1 (PAMG-1) rapid immunoassay with conventional standard methods for the diagnosis of rupture of membranes (ROM). MATERIAL AND METHODS: A prospective observational study was performed in patients with symptoms or signs of premature rupture of membranes (PROM) at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University. Conventional standard methods were performed to establish the diagnosis and were compared with PAMG-1 immunoassay results. ROM was diagnosed if visualization of fluid leaking from the cervical os or two of the following three conditions were present: positive nitrazine test, ferning test, and nile blue test. The diagnosis of ROM was confirmed by reviewing the medical records after delivery. RESULTS: One hundred patients (gestational age 36.5+/-3.5weeks, range 22-41weeks of gestation) were recruited into the study. Seventy-six percent were preterm and 24% were at term. PAMG-1 immunoassay had a sensitivity of 97.2%, specificity of 69%, positive predictive value (PPV) of 90.8%, negative predictive value (NPV) of 90.9% and an accuracy of 89%. In contrast, conventional combined standard methods had a sensitivity of 88.7%, specificity of 96.6%, PPV of 98.4%, NPV of 77.8%, and accuracy of 91% for the diagnosis of ROM. CONCLUSION: PAMG-1 immunoassay is a rapid method for the diagnosis of ROM. PAMG-1 has a higher sensitivity than conventional standard methods for the diagnosis of ROM. PMID- 22070531 TI - Amelioration of amyloid beta-induced cognitive deficits by Zataria multiflora Boiss. essential oil in a rat model of Alzheimer's disease. AB - INTRODUCTION: The limitations of current Alzheimer's disease (AD) therapeutics have prompted investigation into innovative therapeutics focused on antiinflammatory, antioxidant, and neuroprotective agents including those from medicinal plants. Numerous plants have been tested for their potential for alleviating symptoms of AD. AIMS: Zataria multiflora Boiss. (ZM) a member of Lamiaceae family has been used in Iranian traditional medicine for its beneficial effects on mental abilities. Therefore, the effect of its essential oil was evaluated in a rat model of AD. METHODS: Amyloid beta-protein (Abeta) fragment 25 35 was injected bilaterally in the CA1 region of rats hippocampus and the effect of different doses of ZM essential oil (50, 100, or 200 MUL/kg) on cognitive function was investigated in the Morris water maze. Acute toxicity of the essential oil was also studied. RESULTS: The results showed increases in escape latency, traveled distance, heading angle, and decreases in target quadrant entries in Abeta-received groups as compared to the control group. This impairment was reversed by ZM essential oil. The results of acute toxicity testing revealed that the calculated LD50 (1264.9 MUL/kg) is much higher than the therapeutic dose (100 MUL/kg). CONCLUSIONS: It seems that antioxidant, antiinflammatory, and anticholinesterase activities of ZM or its main constituents might contribute to its beneficial effects in this model. Our findings suggest that ZM may be a potentially valuable source of natural therapeutic agents for the treatment of AD. However, further investigations are necessary to establish its clinical efficacy and potential toxicity, before any recommendations concerning its use as a medication in the treatment of AD. PMID- 22070534 TI - Minimally invasive approach in the management of upper- urinary-tract tumours. AB - OBJECTIVE: Nephroureterectomy with bladder cuff excision has been the gold standard treatment for upper tract transitional cell carcinoma (UTTCC) for more than 60 years. However, endoscopic treatment of urothelial tumours of renal pelvis and ureter is gaining acceptance as a conservative treatment modality. MATERIAL AND METHODS: A review in the English language of the Medline and Pub Med databases was performed using the keywords upper urinary tract transitional cell carcinoma and endoscopic management. There was a particular emphasis on treatment outcomes from published series. RESULTS: Endoscopic treatment of UTTCC alone for high-grade tumours is not advised owing to high rates of both local recurrence and disease progression, while many authors do not recommend primary endoscopic management of UTTCC in elective situations if pathological analysis and tumour grade cannot be obtained. CONCLUSION: Endourological management of UTTCC has become an accepted treatment option in highly selected patients, provided long term close surveillance to detect and treat recurrences is ensured. PMID- 22070532 TI - Structuring and validating a cost-effectiveness model of primary asthma prevention amongst children. AB - BACKGROUND: Given the rising number of asthma cases and the increasing costs of health care, prevention may be the best cure. Decisions regarding the implementation of prevention programmes in general and choosing between unifaceted and multifaceted strategies in particular are urgently needed. Existing trials on the primary prevention of asthma are, however, insufficient on their own to inform the decision of stakeholders regarding the cost-effectiveness of such prevention strategies. Decision analytic modelling synthesises available data for the cost-effectiveness evaluation of strategies in an explicit manner. Published reports on model development should provide the detail and transparency required to increase the acceptability of cost-effectiveness modelling. But, detail on the explicit steps and the involvement of experts in structuring a model is often unevenly reported. In this paper, we describe a procedure to structure and validate a model for the primary prevention of asthma in children. METHODS: An expert panel was convened for round-table discussions to frame the cost-effectiveness research question and to select and structure a model. The model's structural validity, which indicates how well a model reflects the reality, was determined through descriptive and parallel validation. Descriptive validation was performed with the experts. Parallel validation qualitatively compared similarity between other published models with different decision problems. RESULTS: The multidisciplinary input of experts helped to develop a decision-tree structure which compares the current situation with screening and prevention. The prevention was further divided between multifaceted and unifaceted approaches to analyse the differences. The clinical outcome was diagnosis of asthma. No similar model was found in the literature discussing the same decision problem. Structural validity in terms of descriptive validity was achieved with the experts and was supported by parallel validation. CONCLUSIONS: A decision-tree model developed with experts in round-table discussions benefits from a systematic and transparent approach and the multidisciplinary contributions of the experts. Parallel validation provides a feasible alternative to validating novel models. The process of structuring and validating a model presented in this paper could be a useful guide to increase transparency, credibility, and acceptability of (future, novel) models when experts are involved. PMID- 22070535 TI - Significance of cytomegalovirus infection in the failure of native arteriovenous fistula. AB - High cytomegalovirus (CMV) IgG levels have been identified as a risk factor for arteriovenous fistula (AVF) failure. None of the 68 patents in our study were CMV IgM positive, although 96% were CMV IgG positive. CMV antigens were detected in the radial artery or cephalic vein of 46% of patients who received an AVF. The presence of CMV antigens or high serum CMV IgG levels had no prognostic value for AVF failure. PMID- 22070536 TI - Sphingosine in plants--more riddles from the Sphinx? AB - * Sphingolipids are emerging as important mediators of cellular and developmental processes in plants, and advances in lipidomics have yielded a wealth of information on the composition of plant sphingolipidomes. Studies using Arabidopsis thaliana showed that the dihydroxy long-chain base (LCB) is desaturated at carbon position 8 (d18:1(Delta8)). This raised important questions on the role(s) of sphingosine (d18:1(Delta4)) and sphingosine-1-phosphate (d18:1(Delta4)-P) in plants, as these LCBs appear to be absent in A. thaliana. * Here, we surveyed 21 species from various phylogenetic groups to ascertain the position of desaturation of the d18:1 LCB, in order to gain further insights into the prevalence of d18:1(Delta4) and d18:1(Delta8) in plants. * Our results showed that d18:1(Delta8) is common in gymnosperms, whereas d18:1(Delta4) is widespread within nonseed land plants and the Poales, suggesting that d18:1(Delta4) is evolutionarily more ancient than d18:1(Delta8) in Viridiplantae. Additionally, phylogenetic analysis indicated that the sphingolipid Delta4-desaturases from Viridiplantae form a monophyletic group, with Angiosperm sequences falling into two distinct clades, the Eudicots and the Poales. * We propose that efforts to elucidate the role(s) of d18:1(Delta4) and d18:1(Delta4)-P should focus on genetically tractable Viridiplantae species where the d18:1 LCB is desaturated at carbon position 4. PMID- 22070537 TI - My farewell to the Journal of Medicinal Chemistry. PMID- 22070538 TI - Applicability and results of Maastricht type 2 donation after cardiac death liver transplantation. AB - Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end-stage liver disease and cold and reperfusion warm ischemic times were 55 years (49-60), 19 (14-21) and 380 (325-430) and 30 min (26-35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One-year recipient and graft survivals were 82% and 70%, respectively (median follow-up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly. PMID- 22070539 TI - Historical aspects of Danish psychiatry. PMID- 22070540 TI - Melatonin-dependent timing of seasonal reproduction by the pars tuberalis: pivotal roles for long daylengths and thyroid hormones. AB - Most mammals living at temperate latitudes exhibit marked seasonal variations in reproduction. In long-lived species, it is assumed that timely physiological alternations between a breeding season and a period of sexual rest depend upon the ability of day length (photoperiod) to synchronise an endogenous timing mechanism called the circannual clock. The sheep has been extensively used to characterise the time-measurement mechanisms of seasonal reproduction. Melatonin, secreted only during the night, acts as the endocrine transducer of the photoperiodic message. The present review is concerned with the endocrine mechanisms of seasonal reproduction in sheep and the evidence that long day length and thyroid hormones are mandatory to their proper timing. Recent evidence for a circadian-based molecular mechanism within the pars tuberalis of the pituitary, which ties the short duration melatonin signal reflecting long day length to the hypothalamic increase of triiodothyronine (T3) through a thyroid stimulating hormone/deiodinase2 paracrine mechanism is presented and evaluated in this context. A parallel is also drawn with the golden hamster, a long-day breeder, aiming to demonstrate that features of seasonality appear to be phylogenetically conserved. Finally, potential mechanisms of T3 action within the hypothalamus/median eminence in relationship to seasonal timing are examined. PMID- 22070541 TI - Aims and results of the NIMH systematic treatment enhancement program for bipolar disorder (STEP-BD). AB - The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was funded as part of a National Institute of Mental Health initiative to develop effectiveness information about treatments, illness course, and assessment strategies for severe mental disorders. STEP-BD studies were planned to be generalizable both to the research knowledge base for bipolar disorder and to clinical care of bipolar patients. Several novel methodologies were developed to aid in illness characterization, and were combined with existing scales on function, quality of life, illness burden, adherence, adverse effects, and temperament to yield a comprehensive data set. The methods integrated naturalistic treatment and randomized clinical trials, which a portion of STEP-BD participants participated. All investigators and other researchers in this multisite program were trained in a collaborative care model with the objective of retaining a high percentage of enrollees for several years. Articles from STEP BD have yielded evidence on risk factors impacting outcomes, suicidality, functional status, recovery, relapse, and caretaker burden. The findings from these studies brought into question the widely practiced use of antidepressants in bipolar depression as well as substantiated the poorly responsive course of bipolar depression despite use of combination strategies. In particular, large studies on the characteristics and course of bipolar depression (the more pervasive pole of the illness), and the outcomes of treatments concluded that adjunctive psychosocial treatments but not adjunctive antidepressants yielded outcomes superior to those achieved with mood stabilizers alone. The majority of patients with bipolar depression concurrently had clinically significant manic symptoms. Anxiety, smoking, and early age of bipolar onset were each associated with increased illness burden. STEP-BD has established procedures that are relevant to future collaborative research programs aimed at the systematic study of the complex, intrinsically important elements of bipolar disorders. PMID- 22070542 TI - Stark control of a chiral fluoroethylene derivative. AB - Hydrogen dissociation is an unwanted competing pathway if a torsional motion around the C?C double bond in a chiral fluoroethylene derivative, namely (4 methylcyclohexylidene) fluoromethane (4MCF), is to be achieved. We show that the excited state H-dissociation can be drastically diminished on time scales long enough to initiate a torsion around the C?C double bond using the nonresonant dynamic Stark effect. Potential energy curves, dipoles, and polarizabilities for the regarded one-dimensional reaction coordinate are calculated within the CASSCF method. The influence of the excitation and the laser control field is then simulated using wave packet dynamics. PMID- 22070543 TI - The medicines management needs of carers during an episode of mental health crisis. PMID- 22070544 TI - Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling. AB - Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes. PMID- 22070546 TI - Signs of cross-seeding: aortic medin amyloid as a trigger for protein AA deposition. AB - The highly diverse deposition pattern displayed by systemic amyloidoses, sometimes within the same amyloid disease, remains unexplained. The localized medin (AMed) amyloidosis develops from the precursor protein lactadherin and deposits in the media of the thoracic aorta in almost all individuals above 50 years of age. Given its high prevalence in the population, and the fact that systemic amyloidoses also deposit in the aorta, led us to investigate whether AMed amyloid could influence the tissue distribution of serum amyloid A derived (AA) amyloidosis. Seven aortas from patients with diagnosed systemic AA amyloidosis were investigated. Four displayed partial co-localization between medin and AA aggregates when examined with double-labeling immunofluorescence. Furthermore, in vitro studies showed that AMed amyloid-like fibrils promote the aggregation of protein AA into fibrils. The findings indicate that the highly frequent "senile" amyloidoses may have the potential to initiate fibril formation of the more uncommon amyloidoses by a cross-seeding mechanism. PMID- 22070545 TI - The palladium catalyzed asymmetric addition of oxindoles and allenes: an atom economical versatile method for the construction of chiral indole alkaloids. AB - The Pd-catalyzed asymmetric allylic alkylation (AAA) is one of the most useful and versatile methods for asymmetric synthesis known in organometallic chemistry. Development of this reaction over the past 30 years has typically relied on the use of an allylic electrophile bearing an appropriate leaving group to access the reactive Pd(pi-allyl) intermediate that goes on to the desired coupling product after attack by the nucleophile present in the reaction. Our group has been interested in developing alternative approaches to access the reactive Pd(pi allyl) intermediate that does not require the use of an activated electrophile, which ultimately generates a stoichiometric byproduct in the reaction that is derived from the leftover leaving group. Along these lines, we have demonstrated that allenes can be used to generate the reactive Pd(pi-allyl) intermediate in the presence of an acid cocatalyst, and this system is compatible with nucleophiles to allow for formation of formal AAA products by Pd-catalyzed additions to allenes. This article describes our work regarding the use of oxindoles as carbon-based nucleophiles in a Pd-catalyzed asymmetric addition of oxindoles to allenes (Pd-catalyzed hydrocarbonation of allenes). By using the chiral standard Trost ligand (L1) and 3-aryloxindoles as nucleophiles, this hydrocarbonation reaction provides products with two vicinal stereocenters, with one being quaternary, in excellent chemo-, regio-, diastereo-, and enantioselectivities in high chemical yields. PMID- 22070547 TI - Review: personalized mice: modelling the molecular heterogeneity of medulloblastoma. AB - Medulloblastoma, the most common malignant paediatric brain tumour, is thought to arise from mutations in progenitors or stem cells in the cerebellum. Recent molecular analyses have highlighted the heterogeneity of these tumours, and demonstrated that they can be classified into at least four major subtypes that differ in terms of gene expression, genomic gains and losses, epidemiology and patient outcome. Along with analysis of human tumours, a variety of animal models of medulloblastoma have been developed using transgenic and knockout technology as well as somatic gene delivery. These models have provided valuable insight into the origins of the disease and the signalling pathways that control tumour growth. But the degree to which current models recapitulate the heterogeneity of the human disease remains unclear. Here we review the recent literature on the genomics of medulloblastoma and discuss the relationship of mouse models to the subtypes of the disease. Judicious use of existing models, and generation of additional models for poorly studied subtypes of medulloblastoma, will increase our understanding of tumour biology and allow evaluation of novel approaches to treatment of the disease. PMID- 22070548 TI - Investigating the impact of psychosocial risks and occupational stress on psychiatric hospital nurses' mental well-being in Japan. AB - A cross-sectional survey was conducted, with the aim to examine what stressors in the workplace and demographic factors were associated with signs and symptoms of poor well-being among psychiatric nurses. A structured questionnaire was distributed to nurses within six psychiatric hospitals in Japan. Information was collected on demographic information, work characteristics and two dimensions of well-being: feeling uptight and emotional exhaustion. Three hundred and sixty-one questionnaires were completed by participants. High rates of emotional exhaustion in psychiatric nurses were found to be predicted by young age, high psychological demands paired with low social support in the workplace, job strain (a proxy to occupational stress) and job strain paired with low social support. In addition, high rates of being tense/uptight were associated with high psychological job demand, low psychological job control, low social support in the workplace, high job strain and high job strain paired with low social support. The current study has found evidence of significant relationships between demographic factors and several work and organizational stressors and poor mental health among Japanese psychiatric nurses. PMID- 22070549 TI - What can virtual patient simulation offer mental health nursing education? AB - This paper discusses the use of simulation in nursing education and training, including potential benefits and barriers associated with its use. In particular, it addresses the hitherto scant application of diverse simulation devices and dedicated simulation scenarios in psychiatric and mental health nursing. It goes on to describe a low-cost, narrative-based virtual patient simulation technique which has the potential for wide application within health and social care education. An example of the implementation of this technology in a web-based pilot course for acute mental health nurses is given. This particular virtual patient technique is a simulation type ideally suited to promoting essential mental health nursing skills such as critical thinking, communication and decision making. Furthermore, it is argued that it is particularly amenable to e learning and blended learning environments, as well as being an apt tool where multilingual simulations are required. The continued development, implementation and evaluation of narrative virtual patient simulations across a variety of health and social care programmes would help ascertain their success as an educational tool. PMID- 22070550 TI - Silver nanoparticles and total aerosols emitted by nanotechnology-related consumer spray products. AB - Products containing silver nanoparticles are entering the market rapidly, but little is known about the potential for inhalation exposure to nanosilver. The objectives of this work were to characterize the emissions of airborne particles from consumer products that claim to contain silver nanoparticles or ions, determine the relationship between emissions and the products' liquid characteristics, and assess the potential for inhalation exposure to silver during product use. Three products were investigated: an antiodor spray for hunters, a surface disinfectant, and a throat spray. Products emitted 0.24-56 ng of silver in aerosols per spray action. The plurality of silver was found in aerosols 1-2.5 MUm in diameter for two products. Both the products' liquid characteristics and the bottles' spray mechanisms played roles in determining the size distribution of total aerosols, and the size of silver-containing aerosols emitted by the products was largely independent of the silver size distributions in the liquid phase. Silver was associated with chlorine in most samples. Results demonstrate that the normal use of silver-containing spray products carries the potential for inhalation of silver-containing aerosols. Exposure modeling suggests that up to 70 ng of silver may deposit in the respiratory tract during product use. PMID- 22070551 TI - MR spectroscopy and atrophy in Gluten, Friedreich's and SCA6 ataxias. AB - BACKGROUND: Previous work using proton MR spectroscopy ((1)H-MRS) of the cerebellum in the ataxias suggested that (1)H-MRS abnormalities and atrophy do not necessarily occur concurrently. AIMS: To investigate the spectroscopic features of different types of ataxias. METHODS: Using a clinical MR system operating at 1.5T, we performed (1)H-MRS with a single voxel placed over the right dentate nucleus in 22 patients with gluten ataxia (GA), six patients with Friedreich's ataxia (FA), six patients with spinocerebellar ataxia type 6 (SCA6) and 21 healthy volunteers. Atrophy of the vermis and hemispheres on standard MRI was rated by a neuroradiologist. Any interaction between atrophy and (1)H-MRS was analysed for the three groups of patients and controls. RESULTS: Patients with GA had significant atrophy of the vermis and hemispheres as well as abnormal (1)H MRS. Patients with SCA6 had more severe overall atrophy of the vermis and hemispheres, but relatively preserved N-acetyl-aspartate/creatine (NAA/Cr). The FA group showed significant atrophy of only the superior vermis with normal (1)H MRS. CONCLUSIONS: This study suggests that (1)H-MRS of the cerebellum in patients with ataxia provides information in addition to the presence of atrophy. There are significant (1)H-MRS differences amongst different types of ataxia with interesting correlations between atrophy and NAA/Cr. PMID- 22070552 TI - Enamel matrix derivative: a review of cellular effects in vitro and a model of molecular arrangement and functioning. AB - BACKGROUND: Enamel matrix derivative (EMD), the active component of Emdogain(r), is a viable option in the treatment of periodontal disease owing to its ability to regenerate lost tissue. It is believed to mimic odontogenesis, though the details of its functioning remain the focus of current research. OBJECTIVE: The aim of this article is to review all relevant literature reporting on the composition/characterization of EMD as well as the effects of EMD, and its components amelogenin and ameloblastin, on the behavior of various cell types in vitro. In this way, insight into the underlying mechanism of regeneration will be garnered and utilized to propose a model for the molecular arrangement and functioning of EMD. METHODS: A review of in vitro studies of EMD, or components of EMD, was performed using key words "enamel matrix proteins" OR "EMD" OR "Emdogain" OR "amelogenin" OR "ameloblastin" OR "sheath proteins" AND "cells." Results of this analysis, together with current knowledge on the molecular composition of EMD and the structure and regulation of its components, are then used to present a model of EMD functioning. RESULTS: Characterization of the molecular composition of EMD confirmed that amelogenin proteins, including their enzymatically cleaved and alternatively spliced fragments, dominate the protein complex (>90%). A small presence of ameloblastin has also been reported. Analysis of the effects of EMD indicated that gene expression, protein production, proliferation, and differentiation of various cell types are affected and often enhanced by EMD, particularly for periodontal ligament and osteoblastic cell types. EMD also stimulated angiogenesis. In contrast, EMD had a cytostatic effect on epithelial cells. Full-length amelogenin elicited similar effects to EMD, though to a lesser extent. Both the leucine-rich amelogenin peptide and the ameloblastin peptides demonstrated osteogenic effects. A model for molecular structure and functioning of EMD involving nanosphere formation, aggregation, and dissolution is presented. CONCLUSIONS: EMD elicits a regenerative response in periodontal tissues that is only partly replicated by amelogenin or ameloblastin components. A synergistic effect among the various proteins and with the cells, as well as a temporal effect, may prove important aspects of the EMD response in vivo. PMID- 22070553 TI - Growth, respiration and nutrient acquisition by the arbuscular mycorrhizal fungus Glomus mosseae and its host plant Plantago lanceolata in cooled soil. AB - Although plant phosphate uptake is reduced by low soil temperature, arbuscular mycorrhizal (AM) fungi are responsible for P uptake in many plants. We investigated growth and carbon allocation of the AM fungus Glomus mosseae and a host plant (Plantago lanceolata) under reduced soil temperature. Plants were grown in compartmented microcosm units to determine the impact on both fungus and roots of a constant 2.7 degrees C reduction in soil temperature for 16 d. C allocation was measured using two (13)CO(2) pulse labels. Although root growth was reduced by cooling, AM colonization, growth and respiration of the extraradical mycelium (ERM) and allocation of assimilated (13)C to the ERM were all unaffected; the frequency of arbuscules increased. In contrast, root respiration and (13)C content and plant P and Zn content were all reduced by cooling. Cooling had less effect on N and K, and none on Ca and Mg content. The AM fungus G. mosseae was more able to sustain activity in cooled soil than were the roots of P. lanceolata, and so enhanced plant P content under a realistic degree of soil cooling that reduced plant growth. AM fungi may therefore be an effective means to promote plant nutrition under low soil temperatures. PMID- 22070554 TI - In vivo specific delivery of c-Met siRNA to glioblastoma using cationic solid lipid nanoparticles. AB - RNA interference is a powerful strategy that inhibits gene expression through specific mRNA degradation. In vivo, however, the application of small interfering RNAs (siRNAs) is severely limited by their instability and their poor delivery into target cells and tissues. This is especially true with glioblastomas (GBMs), the most frequent and malignant form of brain tumor, that has limited treatment options due to the largely impenetrable blood-brain barrier. Here, cationic solid lipid nanoparticles (SLN), reconstituted from natural components of protein-free low-density lipoprotein, was conjugated to PEGylated c-Met siRNA. The c-Met siRNA PEG/SLN complex efficiently down-regulated c-Met expression level, as well as decreased cell proliferation in U-87MG in vitro. In orthotopic U-87MG xenograft tumor model, intravenous administration of the complex significantly inhibited c Met expression at the tumor tissue and suppressed tumor growth without showing any systemic toxicity in mice. Use of Cy5.5 conjugated SLN revealed enhanced accumulation of the siRNA-PEG/SLN complexes specifically in the brain tumor. Our data demonstrates the feasibility of using siRNA-PEG/SLN complexes as a potential carrier of therapeutic siRNAs for the systemic treatment of GBM in the clinic. PMID- 22070555 TI - Surgery for fistula-in-ano in a specialist colorectal unit: a critical appraisal. AB - BACKGROUND: Several techniques have been described for the management of fistula in-ano, but all carry their own risks of recurrence and incontinence. We conducted a prospective study to assess type of presentation, treatment strategy and outcome over a 5-year period. METHODS: Between 1st January 2005 and 31st March 2011,247 patients presenting with anal fistulas were treated at the University Hospital Tor Vergata and were included in the present prospective study. Mean age was 47 years (range 16-76 years); minimum follow-up period was 6 months (mean 40, range 6-74 months).Patients were treated using 4 operative approaches: fistulotomy, fistulectomy, seton placement and rectal advancement flap. Data analyzed included: age, gender, type of fistula, operative intervention, healing rate, postoperative complications, reinterventions and recurrence. RESULTS: Etiologies of fistulas were cryptoglandular (n = 218), Crohn's disease (n = 26) and Ulcerative Colitis (n = 3). Fistulae were classified as simple -intersphincteric 57 (23%), low transphincteric 28 (11%) and complex high transphicteric 122 (49%), suprasphincteric 2 (0.8%), extrasphinteric 2 (0.8%), recto-vaginal 7 (2.8%) Crohn 26 (10%) and UC 3 (1.2%).The most common surgical procedure was the placement of seton (62%), usually applied in case of complex fistulae and Crohn's patients.Eighty-five patients (34%) underwent fistulotomy, mainly for intersphincteric and mid/low transphincteric tracts. Crohn's patients were submitted to placement of one or more loose setons.The main treatment successfully eradicated the primary fistula tract in 151/247 patients (61%). Three cases of major incontinence (1.3%) were detected during the follow up period; Furthermore, three patients complained minor incontinence that was successfully treated by biofeedback and permacol injection into the internal anal sphincter. CONCLUSIONS: This prospective audit demonstrates an high proportion of complex anal fistulae treated by seton placement that was the most common surgical technique adopted to treat our patients as a first line. Nevertheless, a good outcome was achieved in the majority of patients with a limited rate of faecal incontinence (6/247 = 2.4%). New technologies provide promising alternatives to traditional methods of management particularly in case of complex fistulas. There is, however, a real need for high-quality randomized control trials to evaluate the different surgical and non surgical treatment options. PMID- 22070556 TI - Short-course antibiotics for prosthetic joint infections treated with prosthesis retention. AB - The purpose of the present study was to evaluate the significance of shortening the antibiotic treatment duration in prosthetic joint infections (PJI) treated with debridement, antibiotics and implant retention (DAIR). In April 2006 we shortened the total antibiotic treatment duration in total knee arthroplasty (TKA) PJIs from 6 months to 3 months and in total hip arthroplasty (THA) PJIs from 3 months to 2 months. All patients with TKA or THA PJI treated with DAIR between February 2001 and August 2009 were reviewed retrospectively. There were 132 patients treated with DAIR, of whom 86 (65%) completed the antibiotic therapy and were therefore eligible for comparison concerning the length of antibiotic treatment. There were 32 (37%) THA and 54 (63%) TKA PJIs in the comparison. The treatment succeeded in 34 (89.5%) patients treated with longer antibiotic treatment and in 42 (87.5%) of those treated with shorter antibiotic treatment (p 0.78). Our conclusion is that if the patient completes the antibiotic therapy, treatment duration of 3 months in TKA PJIs and 2 months in THA PJIs is as good as longer antibiotic treatment of 6 months or 3 months, respectively, in patients treated with DAIR. PMID- 22070557 TI - Role of Hounsfield units to distinguish pseudo-subarachnoid hemorrhage. PMID- 22070558 TI - Chemical pneumonitis after intravenous injection of isoparaffin: Characteristic clinico-radiologic findings. AB - A 23-year-old man presented with chest pain after intravenous (IV) injection of isoparaffin (C12-C13, 99%). This report describes the chest computed tomography (CT) pattern of chemical pneumonitis after IV isoparaffin injection. When injected IV, hydrocarbon can cause chemical pneumonitis, mimicking pulmonary infarction on chest CT. The CT pattern is attributable to diffusion of hydrocarbons through systemic veins into small pulmonary arteries and capillary beds, causing extensive local reactions and chemical pneumonitis or pleuritis. PMID- 22070559 TI - Inorganic mercury poisoning associated with skin-lightening cosmetic products. AB - INTRODUCTION: Mercury and mercury salts, including mercurous chloride and mercurous oxide, are prohibited for use in cosmetic products as skin-lightening agents because of their high toxicity. Yet, the public continue to have access to these products. METHODS: Reports of skin-lightening cosmetic products containing mercury and cases of mercury poisoning following the use of such products were identified using Medline (1950 - 28 March 2011) with mercury, mercury compounds, mercury poisoning, cosmetics and skin absorption as the subject headings. These searches identified 118 citations of which 31 were relevant. TOXICOKINETICS: The rate of dermal absorption increases with the concentration of mercury and prior hydration of the skin. The degree of dermal absorption varies with the skin integrity and lipid solubility of the vehicle in the cosmetic products. Ingestion may occur after topical application around the mouth and hand-to-mouth contact. After absorption, inorganic mercury is distributed widely and elimination occurs primarily through the urine and feces. With long-term exposure, urinary excretion is the major route of elimination. The half-life is approximately 1-2 months. FEATURES: The kidneys are the major site of inorganic mercury deposition; renal damage includes reversible proteinuria, acute tubular necrosis and nephrotic syndrome. Gastrointestinal symptoms include a metallic taste, gingivostomatitis, nausea and hypersalivation. Although penetration of the blood-brain barrier by inorganic mercury is poor, prolonged exposure can result in central nervous system (CNS) accumulation and neurotoxicity. Inorganic mercury poisoning following the use of skin-lightening creams has been reported from Africa, Europe, USA, Mexico, Australia and Hong Kong. Nephrotic syndrome (mainly due to minimal change or membranous nephropathy) and neurotoxicity were the most common presenting features. As mercury-containing cosmetic products can contaminate the home, some close household contacts were also reported to have elevated urine mercury concentrations. ASSESSMENT: Prevention from further exposure is the first step. Cream users and their close contacts should be evaluated for evidence of mercury exposure, the presence of target organ damage and the need for chelation treatment. Laboratory evaluation of affected subjects should include a complete blood count, serum electrolytes, liver and renal function tests, urinalysis, urine and blood mercury concentrations. Since blood mercury concentrations tend to return to normal within days of exposure, blood samples are useful primarily in short-term, higher-level exposures. Estimation of the urine mercury concentration is the best marker of exposure to inorganic mercury and indicator of body burden. A 24-hour urine for measurement of mercury excretion is preferred; a spot urine mercury concentration should be corrected for creatinine output. MANAGEMENT: Chelation therapy is indicated in patients with features of mercury poisoning and elevated blood and/or urine mercury concentrations. Unithiol (2,3-dimercapto-1-propanesulfonic acid, DMPS) is the preferred antidote though succimer (dimercaptosuccinic acid, DMSA) has also been employed. CONCLUSIONS: The use of mercury in cosmetic products should be strictly prohibited. The public should be warned not to use such products as their use can result in systemic absorption and accumulation of mercury causing renal, gastrointestinal and CNS toxicity. PMID- 22070560 TI - Acute amiodarone poisoning occurring twice in the same subject. PMID- 22070561 TI - Second case of the use of intravenous fat emulsion therapy for propafenone toxicity. PMID- 22070563 TI - Effects of different surface pre-treatments on the bond strength of adhesive resin cement to quartz fiber post. AB - OBJECTIVE: The purpose of this study was to evaluate the effect of mechanical and chemical surface treatment methods on the bond strength of resin cement to fiber post. MATERIALS AND METHODS: The roots of 36 maxillary central incisor teeth were mounted in auto polymerized acrylic resin blocks (10 * 15 mm) and the root canals were enlarged with the drills of post system (2.1 mm width, 12 mm length). Thirty six fiber posts were randomly assigned to one of the following surface conditioning methods: silane coupling agent, methylene chloride etching, 24% hydrogen peroxide etching, air abrasion with 50 um Al(2)O(3), 1-3 um synthetic diamond particles and silica coating with 30 um SiO(x). Fiber posts were cemented to the root canals with adhesive resin cement (Panavia F 2.0). Three slices of 1.5 mm thick were obtained from each root. Push-out tests were performed with a universal testing machine. The data were analyzed with one-way analysis of variance (ANOVA) and Tukey HSD tests (alpha = 0.05). The effect of the surface treatments were examined under a scanning electron microscope (SEM) and surface roughness were evaluated with a profilometer. RESULTS: Surface pre-treatment methods affected the bond strength (p < 0.05). The highest bond strengths were obtained by air abrasion with synthetic diamond particles, the lowest bond strength were obtained by etching with methylene chloride (p < 0.05). CONCLUSION: Mechanical surface pre-treatment methods showed higher bond strength values than chemical methods. Synthetic diamond particles may be an alternative method to increase resin cement bonding on the quartz fiber post surfaces. PMID- 22070562 TI - Selective oestrogen receptor modulators differentially potentiate brain mitochondrial function. AB - The mitochondrial energy-transducing capacity of the brain is important for long term neurological health and is influenced by endocrine hormone responsiveness. The present study aimed to determine the role of oestrogen receptor (ER) subtypes in regulating mitochondrial function using selective agonists for ERalpha (propylpyrazoletriol; PPT) and ERbeta (diarylpropionitrile; DPN). Ovariectomised female rats were treated with 17beta-oestradiol (E(2) ), PPT, DPN or vehicle control. Both ER selective agonists significantly increased the mitochondrial respiratory control ratio and cytochrome oxidase (COX) activity relative to vehicle. Western blots of purified whole brain mitochondria detected ERalpha and, to a greater extent, ERbeta localisation. Pre-treatment with DPN, an ERbeta agonist, significantly increased ERbeta association with mitochondria. In the hippocampus, DPN activated mitochondrial DNA-encoded COX I expression, whereas PPT was ineffective, indicating that mechanistically ERbeta, and not ERalpha, activated mitochondrial transcriptional machinery. Both selective ER agonists increased protein expression of nuclear DNA-encoded COX IV, suggesting that activation of ERbeta or ERalpha is sufficient. Selective ER agonists up-regulated a panel of bioenergetic enzymes and antioxidant defence proteins. Up-regulated proteins included pyruvate dehydrogenase, ATP synthase, manganese superoxide dismutase and peroxiredoxin V. In vitro, whole cell metabolism was assessed in live primary cultured hippocampal neurones and mixed glia. The results of analyses conducted in vitro were consistent with data obtained in vivo. Furthermore, lipid peroxides, accumulated as a result of hormone deprivation, were significantly reduced by E(2) , PPT and DPN. These findings suggest that the activation of both ERalpha and ERbeta is differentially required to potentiate mitochondrial function in brain. As active components in hormone therapy, synthetically designed oestrogens as well as natural phyto-oestrogen cocktails can be tailored to improve brain mitochondrial endpoints. PMID- 22070564 TI - Olfactory processing in schizophrenia, non-ill first-degree family members, and young people at-risk for psychosis. AB - OBJECTIVES: While deficits in odor identification and discrimination have been reported in schizophrenia, few studies have examined the relative specificity of these deficits in patients and at-risk youth. METHOD: Sniffin' Sticks odor identification and discrimination were assessed in schizophrenia outpatients and non-ill first-degree relatives (Study One), as well as youth at clinical (CR) or genetic (GR) risk for schizophrenia (Study Two). Scores were z-transformed, using the performance of a demographically-matched adult or adolescent comparison group. RESULTS: Patients and relatives were impaired on odor identification, but odor discrimination impairment was limited to the patient group. A similar pattern of impairment emerged in at-risk youth. GR youth were impaired on odor identification but not discrimination, while CR youth were impaired on both tasks. In patients, olfactory impairment was correlated with negative symptomatology. CONCLUSIONS: To our knowledge, this is the first study to show that CR youth are impaired on both olfactory tasks, as observed in adult schizophrenia patients. GR youth were impaired only on odor identification like their adult counterparts. These data suggest that odor identification impairment, in isolation, may represent a genetic marker of vulnerability for schizophrenia, while odor discrimination deficits may be a biomarker associated with the development of psychosis. PMID- 22070566 TI - Uterus-like mass of ovarian ligament: Image diagnosis and management by laparoendoscopic single-site surgery. AB - Uterus-like mass composed of a cavity lined by mucosa resembling endometrium and surrounding smooth muscle layer simulating myometrium is an extremely rare disease entity of which the histogenesis is presently unknown. A 39-year-old, gravida 2, para 2, woman presented with sudden onset of lower abdominal pain and was found to have left adnexal mass with unusual image diagnostic appearance. The adnexal mass arising from the left ovarian ligament was excised by laparoendoscopic single-site surgery. Histopathological diagnosis was uterus-like mass of ovarian ligament. PMID- 22070565 TI - A novel pathway of chronic allograft rejection mediated by NK cells and alloantibody. AB - Chronic allograft vasculopathy (CAV) in murine heart allografts can be elicited by adoptive transfer of donor specific antibody (DSA) to class I MHC antigens and is independent of complement. Here we address the mechanism by which DSA causes CAV. B6.RAG1(-/-) or B6.RAG1(-/-)C3(-/-) (H-2(b)) mice received B10.BR (H-2(k)) heart allografts and repeated doses of IgG2a, IgG1 or F(ab')(2) fragments of IgG2a DSA (anti-H-2(k)). Intact DSA regularly elicited markedly stenotic CAV in recipients over 28 days. In contrast, depletion of NK cells with anti-NK1.1 reduced significantly DSA-induced CAV, as judged morphometrically. Recipients genetically deficient in mature NK cells (gamma-chain knock out) also showed decreased severity of DSA-induced CAV. Direct NK reactivity to the graft was not necessary. F(ab')(2) DSA fragments, even at doses twofold higher than intact DSA, were inactive. Graft microvascular endothelial cells responded to DSA in vivo by increased expression of phospho-extracellular signal-regulated kinase (pERK), a response not elicited by F(ab')(2) DSA. We conclude that antibody mediates CAV through NK cells, by an Fc dependent manner. This new pathway adds to the possible mechanisms of chronic rejection and may relate to the recently described C4d-negative chronic antibody-mediated rejection in humans. PMID- 22070567 TI - Intelligence is only one human attribute: an introduction to the festschrift in honour of Trevor Parmenter, What is intelligence? What is intellectual disability? PMID- 22070570 TI - New application for expanded porphyrins: sapphyrin and heterosapphyrins as inhibitors of Leishmania parasites. AB - Sapphyrins and a series of related porphyrinoid macrocycles have been investigated as potential agents for the treatment of leishmaniasis. The effectiveness of the compounds was evaluated in vitro upon incubation with Leishmania tarentolae or L. panamensis amastigotes and promastigotes. Their effectiveness was also assessed against intracellular L. panamensis. The cytotoxicity of the compounds was evaluated in vitro using the U937 human promonocyte cell line. Effectiveness and cytotoxicity were assessed in the presence and absence of visible light to assess the photodynamic activity of the compounds. Sapphyrin and two related heterosapphyrins were shown to be particularly effective as inhibitors of Leishmania. A photodynamic effect was observed, which may be attributed to the formation of reactive oxygen species. Yields of singlet oxygen ((1)O(2)) produced were determined in ethanol solutions by direct measurement of (1)O(2) phosphorescence. Confocal microscopy demonstrated that sapphyrin and related macrocycles were taken up by the Leishmania cells and that their presence induces the formation of mitochondrial superoxide. Sapphyrins have been widely investigated as anticancer agents and we here show activity against the Leishmania parasites. PMID- 22070571 TI - Controlled intracellular release of doxorubicin in multidrug-resistant cancer cells by tuning the shell-pore sizes of mesoporous silica nanoparticles. AB - In this work, hollow mesoporous silica nanoparticles (HMSNs) with three pore sizes were manufactured to control the drug release rate, and the biological roles of these HMSNs were evaluated in multidrug-resistant (MDR) cancer cells. As novel pore-size-controllable inorganic materials, HMSNs showed negligible cytotoxicity and efficient cellular uptake toward drug-sensitive MCF-7 and drug resistant MCF-7/ADR cells. Doxorubicin (DOX)-loaded HMSNs (DMSNs) not only demonstrated effective drug loading and a pH-responsive drug release character but also exhibited pore-size-dependent and sustained drug release performance in both in vitro and intracellular drug release experiments. In addition, DMSNs exhibited pore-size-dependent anticancer activity against MCF-7/ADR cells. DMSNs with larger pore size could mediate more cellular uptake of DOX and faster intracellular drug release, which led to more intracellular drug accumulation and stronger MDR-reversal effects. The MDR-overcoming mechanism could be due to the efficient cellular uptake, P-gp inhibition, and ATP depletion. These results demonstrate that HMSNs could be a very promising drug delivery system for pore size-controllable drug release and cancer MDR reversion. PMID- 22070572 TI - State of the art: treatment of bipolar disorders. AB - Bipolar disorders are lifelong lasting affective disorders, with an episodic course of the illness in most cases. The lifetime prevalence is around 2-5%, the illness usually appears in early adulthood and causes significant impairment in psychosocial functioning. This is a selective review focusing on recent developments and issues of interest in the psychopharmacological treatment of bipolar disorders. It is based primarily on the results of adequately powered, randomised, controlled trials (RCTs). These studies were systematically retrieved by means of a Medline search. The past 10 years have led to a broadening of the psychopharmacological treatment options for bipolar disorders. The proof of efficacy for the combination of fluoxetine/olanzapine as well as quetiapine in the acute treatment of bipolar I depression were important steps. While lithium remains the gold standard in the maintenance treatment of bipolar disorders, valproate, olanzapine, lamotrigine, aripiprazole, and quetiapine have been shown efficacious for this indication, with quetiapine possessing the broadest approval status of all drugs for the different treatment phases of this illness. Despite this progress there remains a huge demand regarding new compounds for nearly every area in the psychopharmacological treatment of bipolar disorders. In addition new methodological approaches regarding the proof of effectiveness in clinical practice are urgently needed. PMID- 22070573 TI - The secret food diary of a person diagnosed with schizophrenia. AB - The objective was to consider the feasibility of food diaries as a method of understanding the dietary behaviour of people with schizophrenia. Examination of the food diaries completed in 1 week by eight patients with schizophrenia. All the patients were successful in completing the task. Examination of the food diaries revealed that: eating fruit and vegetables was largely absent; there was very little variety in most of the patients' diets; patients relied heavily on convenience food and ready meals for their main meal; as a rule patients followed an ordered mealtime routine; generally patients did not drink enough fluid; they were not big treat eaters; only one patient recorded drinking any alcohol; overall there appeared to be poor diet literacy in our small sample. The results show that on the whole, people with schizophrenia have a poor diet. This could be due to a combination of financial difficulty, lack of skills in food preparation, lack of motivation to prepare food or ignorance of what constitutes a healthy diet. The fact that they all managed to complete the task is perhaps evidence of motivation to improve their health and demonstrates the utility of food diaries in educating this population. PMID- 22070574 TI - In situ kinetic study on hydrothermal transformation of D-glucose into 5 hydroxymethylfurfural through D-fructose with 13C NMR. AB - Kinetics of hydrothermal reaction of D-glucose was investigated at 0.02 M over a temperature range of 120-160 degrees C by applying in situ (13)C NMR spectroscopy. D-Glucose was found to be reversibly transformed first into D fructose (intermediate) and successively into 5-hydroxymethylfurfural (5-HMF) through dehydration. The carbon mass balance has been kept within the detection limit, and no other reaction pathways are present. The hydrothermal reaction of d glucose is thus understood as that of D-fructose in the sense that the D-glucose reaction proceeds only through D-fructose. All the isomers of D-glucose and D fructose were detected by the in situ (13)C NMR in D(2)O: they are the open chains and the pyranoses and furanoses of alpha- and beta-types. The beta-forms are the most stable due to the hydration. For both D-glucose and D-fructose, the isomers are in a rapid equilibrium for each monosaccharide, and they are treated collectively in the kinetic analysis of the slower hydrothermal reactions. The reactions are of the first order with respect to the concentrations of D-glucose and D-fructose, and D-glucose converts to 5-HMF on the order of hours. The kinetic parameters were determined by the in situ method. PMID- 22070575 TI - Two cheers or three for treatment guidelines? Nudging prescribers in right directions. PMID- 22070577 TI - Analysis of transcriptional factors and regulation networks in laryngeal squamous cell carcinoma patients with lymph node metastasis. AB - The present study was to identify and quantitate differentially expressed proteins in laryngeal squamous cell carcinoma (LSCC) tissues with or without lymph node metastasis and to explore transcriptional factors and regulation networks associated with the process. Tissue specimens were taken from 20 patients with LSCC, including 10 cases of LSCC without metastasis LSCC (N0) and 10 cases of LSCC with metastasis LSCC (Nx). Among the 643 unique proteins identified by using iTRAQ labeling and quantitative proteomic technology, 389 proteins showed an abundance change in LSCC (Nx) as compared to LSCC (N0). Cytoskeleton remodeling, cell adhesion, and immune response activation were found to be the main processes in LSCC metastasis. The construction of transcription regulation networks identified key transcription regulators for lymph node metastasis of LSCC, including Sp1, c-myc, and p53, which may affect LSCC metastasis through the epithelial-mesenchymal transition. Furthermore, our results suggest that ubiquitination may be a critical factor in the networks. The present study provides insights into transcriptional factors and regulation networks involved in LSCC metastasis, which may lead to new strategies for treatment of LSCC metastasis. PMID- 22070578 TI - Adoption of an Internet-based patient education programme in psychiatric hospitals. AB - Internet-based patient support systems are widely assumed to predict a future trend in patient education. Coherent information is still lacking on how patient education is adopted in psychiatric hospitals and how information technology is used in it. Our aim was to describe nurses' adoption of an Internet-based patient education programme and the variables explaining it. The study was based on Rogers' model of the diffusion of innovation. The Internet-based patient education sessions were carried out by nurses on nine acute psychiatric inpatient wards in two Finnish hospitals. They were evaluated with reports and analysed statistically. Out of 100 nurses, 83 adopted the programme during the study period. The nurses fell into Rogers' groups, late majority (72%), laggards (17%), early majority (7%), early adopters (3%) and innovators (1%). Three groups were formed according to their activity: laggards, late majority, adopters (including early majority, early adopters, innovators). There was a statistical difference between the nurses' programme adoption between the two hospitals (P= 0.045): more laggards (65% vs. 35%) and adopters (73% vs. 27%) in the same hospital. The findings help to provide insight into the contexts and settings when adopting information technology programmes in the area of mental health care. PMID- 22070579 TI - Noble-metal-free bimetallic nanoparticle-catalyzed selective hydrogen generation from hydrous hydrazine for chemical hydrogen storage. AB - Noble-metal-free nickel-iron alloy nanoparticles exhibit excellent catalytic performance for the complete decomposition of hydrous hydrazine, for which the NiFe nanocatalyst, with equimolar compositions of Ni and Fe, shows 100% hydrogen selectivity in basic solution (0.5 M NaOH) at 343 K. The development of low-cost and high-performance catalysts may encourage the effective application of hydrous hydrazine as a promising hydrogen storage material. PMID- 22070580 TI - Chemical characterization and source apportionment of fine and coarse particulate matter inside the refectory of Santa Maria Delle Grazie Church, home of Leonardo Da Vinci's "Last Supper". AB - The association between exposure to indoor particulate matter (PM) and damage to cultural assets has been of primary relevance to museum conservators. PM-induced damage to the "Last Supper" painting, one of Leonardo da Vinci's most famous artworks, has been a major concern, given the location of this masterpiece inside a refectory in the city center of Milan, one of Europe's most polluted cities. To assess this risk, a one-year sampling campaign was conducted at indoor and outdoor sites of the painting's location, where time-integrated fine and coarse PM (PM(2.5) and PM(2.5-10)) samples were simultaneously collected. Findings showed that PM(2.5) and PM(2.5-10) concentrations were reduced indoors by 88 and 94% on a yearly average basis, respectively. This large reduction is mainly attributed to the efficacy of the deployed ventilation system in removing particles. Furthermore, PM(2.5) dominated indoor particle levels, with organic matter as the most abundant species. Next, the chemical mass balance model was applied to apportion primary and secondary sources to monthly indoor fine organic carbon (OC) and PM mass. Results revealed that gasoline vehicles, urban soil, and wood-smoke only contributed to an annual average of 11.2 +/- 3.7% of OC mass. Tracers for these major sources had minimal infiltration factors. On the other hand, fatty acids and squalane had high indoor-to-outdoor concentration ratios with fatty acids showing a good correlation with indoor OC, implying a common indoor source. PMID- 22070581 TI - Depression in the elderly: study in a rural city in southern Catalonia. AB - Depression and anxiety are the most common psychiatric diseases among the elderly, and frequently go without diagnosis and treatment. However, evidence regarding the prevalence of depression related to the diagnostic systems utilized and the sociocultural variations in the different communities investigated (rural urban) is contradictory. This study aims to evaluate the prevalence of depression in a rural area in the south of Catalonia, analysing the different age groups, identifying the causal factors of depression and determining whether there are gender differences. The descriptive and quantitative study includes 157 women and 160 men. The qualitative study evaluates 14 men and 52 women diagnosed with depression. Our results indicate a high risk of depression in elderly participants of our small rural community. Widowers suffer more depression than widows and the loneliness, illness, and task of caregiver were predictive variables for depression in these elderly men. The loss of the ability to perform activities of daily living associated with ageing has a greater effect on depression disorders in men than in women. PMID- 22070582 TI - Systematic review of cardiovascular disease in women: assessing the risk. AB - Cardiovascular disease is the number one cause of death for women. In an effort to reduce cardiovascular burden for women, identifying risk factors and increasing awareness of sex differences are fundamental. This systematic review examines cardiovascular disease risk for women. A search of the literature was undertaken using key health databases. Search terms used were cardiovascular disease AND women OR gender. Additional references were manually identified from this literature; 58 articles were reviewed in total. On average, cardiovascular disease presents 10 years later in women compared to men. By this time, they are more likely to suffer from more comorbidities, placing them at higher risk. The complexity of cardiovascular disease identification in women is accentuated through atypical symptoms, and has the potential to lead to delayed and/or misdiagnosis. It is clear through identifying sex differentiation in cardiovascular risk factors that there has been an increased awareness of symptom presentation for women. In light of the sex differences in risk factors, sex specific aspects should be more intensively considered in research/practice to improve clinical outcomes for female cardiovascular disease patients. PMID- 22070583 TI - NICE guidance on CardioQ(TM) oesophageal Doppler monitoring. PMID- 22070584 TI - Peri-operative myocardial infarction: time for therapeutic trials. PMID- 22070585 TI - Rheumatoid arthritis and anaesthesia. AB - There has been a great deal of progress in our understanding and management of rheumatoid arthritis in recent years. The peri-operative management of rheumatoid arthritis patients can be challenging and anaesthetists need to be familiar with recent developments and potential risks of this multi system disease. PMID- 22070586 TI - An unusual cause of monitor failure. PMID- 22070587 TI - Problems with expert opinion. PMID- 22070590 TI - Developing expert opinion in airway management. PMID- 22070591 TI - Comparison of Ambu aScope and Olympus re-usable fibrescope. PMID- 22070595 TI - The Clarus Video System (Trachway) intubating stylet for awake intubation. PMID- 22070593 TI - Use of manikins in airway equipment development. PMID- 22070596 TI - Persistent masseter spasm during anaesthesia. PMID- 22070597 TI - Devices designed to avoid wrong route administration of drugs. PMID- 22070598 TI - Poor ampoule colour coding? PMID- 22070599 TI - Use of capnography to confirm correct tracheal intubation during cardiac arrest. PMID- 22070600 TI - Anaesthetists and apps: content and contamination concerns. PMID- 22070601 TI - Is prevention the best treatment? CMV after lung transplantation. AB - Cytomegalovirus (CMV) is the most prevalent opportunistic infection that occurs in lung-transplant recipients. In addition to its direct morbidity, multiple studies have demonstrated that CMV, in particular CMV pneumonia, is associated with an increased risk for chronic graft dysfunction manifested as bronchiolitis obliterans syndrome (BOS) and worse posttransplant survival. Therefore, prevention of CMV remains an important goal to improve long-term lung-transplant outcomes. Although centers often employed 3 months of prophylaxis in at-risk patients after lung transplantation, a significant proportion of patients still developed infection or disease after the discontinuation of prophylaxis, highlighting the need for more effective approaches to CMV prevention. A number of early single-center reports suggested benefit to extending prophylaxis to longer durations, but concerns regarding cost, late-onset CMV disease, viral resistance and bone marrow toxicity limited enthusiasm for longer durations. However, several recent studies including a multicenter, prospective, randomized, double-blinded clinical trial have demonstrated significant benefits to extending CMV prophylaxis beyond 3 months. Although some areas of controversy remain, the clinical implications of these recent studies suggest that extending prophylaxis with valganciclovir up to 12 months is clearly beneficial for CMV prevention after lung transplantation. PMID- 22070602 TI - Executive function predicts risk of falls in older adults without balance impairment. AB - BACKGROUND: Executive dysfunction has previously been found to be a risk factor for falls. The aim of this study is to investigate the association between executive dysfunction and risk of falling and to determine if this association is independent of balance. METHODS: Participants were 188 community-dwelling individuals aged 65 and older. All participants underwent baseline and annual evaluations with review of health history, standardized neurologic examination, neuropsychological testing, and qualitative and quantitative assessment of motor function. Falls were recorded prospectively using weekly online health forms. RESULTS: During 13 months of follow-up, there were 65 of 188 participants (34.6%) who reported at least one fall. Univariate analysis showed that fallers were more likely to have lower baseline scores in executive function than non-fallers (p = 0.03). Among participants without balance impairment we found that higher executive function z-scores were associated with lower fall counts (p = 0.03) after adjustment for age, sex, health status and prior history of falls using negative binomial regression models. This relationship was not present among participants with poor balance. CONCLUSIONS: Lower scores on executive function tests are a risk factor for falls in participants with minimal balance impairment. However, this effect is attenuated in individuals with poor balance where physical or more direct motor systems factors may play a greater role in fall risk. PMID- 22070603 TI - Identification of active and quiescent adipose vascular stromal cells. AB - BACKGROUND AIMS: Recent studies have demonstrated the existence of both active and quiescent stem cells in bone marrow, hair follicle and intestine. We attempted to identify active and quiescent vascular stromal cells (VSC) in adipose tissue. METHODS: For identification of active VSC, adult rats were injected intraperitoneally with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) and their subcutaneous tissue harvested 3 days later. For identification of quiescent VSC, newborn rats were injected intraperitoneally with EdU and their subcutaneous tissue harvested 9 weeks later. The harvested adipose tissues were examined for the co-localization of EdU with VSC marker CD34, smooth muscle marker SMA, endothelial marker RECA and pericyte marker CD140b. RESULTS: In adult rat adipose tissues harvested 3 days after EdU injection, there were 28.80 +/- 8.70 (mean +/- SD) EdU+ cells/100 * microscopic field, and approximately 6.2% of cell nuclei were labeled with EdU. The percentages of EdU+ cells expressing the following markers were approximately: 84 for CD34, 5.6 for RECA (rat endothelial marker), 3.7 for SMA and 14.8 for CD140b. In the adipose tissues of newborn rats that were harvested 9 weeks after EdU injection, the percentages of EdU+ cells expressing the following markers were approximately: 76 for CD34, 1.8 for RECA, 0 for SMA and 12.9 for CD140b. In both the short-term (active) and long-term (quiescent) EdU-labeled adipose tissues, the EdU label was consistently co localized with CD34 and in the proximity of CD140b stain or in the adventitia. CONCLUSIONS: Both active and quiescent VSC expressed CD34 and localized to capillaries and the adventitia of larger blood vessels. PMID- 22070604 TI - Benzimidazolones: a new class of selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulators. AB - A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPARgamma modulators (SPPARgammaMs) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPARgamma full agonist drugs. Structure-activity relationships of these potent and highly selective SPPARgammaMs were studied with a focus on their unique profiles as partial agonists or modulators. A variety of methods, such as X-ray crystallographic analysis, PPARgamma transactivation coactivator profiling, gene expression profiling, and mutagenesis studies, were employed to reveal the differential interactions of these new analogues with PPARgamma receptor in comparison to full agonists. In rodent models of T2DM, benzimidazolone analogues such as (5R)-5-(3-{[3-(5-methoxybenzisoxazol-3 yl)benzimidazol-1-yl]methyl}phenyl)-5-methyloxazolidinedione (51) demonstrated efficacy equivalent to that of rosiglitazone. Side effects, such as fluid retention and heart weight gain associated with PPARgamma full agonists, were diminished with 51 in comparison to rosiglitazone based on studies in two independent animal models. PMID- 22070605 TI - The occurrence of Legionella species other than Legionella pneumophila in clinical and environmental samples in Denmark identified by mip gene sequencing and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. AB - In Denmark, several laboratories use PCR as a routine diagnostic method for Legionnaires' disease, and almost all PCR-positive samples are investigated by culture. From 1993 to 2010, isolates of Legionella species other than Legionella pneumophila were obtained from respiratory samples from 33 patients, and from 1997 to 2010, 42 isolates of Legionella non-pneumophila species were obtained and saved from water samples from 39 different sites in Denmark. Macrophage infectivity potentiator gene (mip) sequencing was used as a reference method to identify the Legionella non-pneumophila species. Only one of the 75 isolates did not meet the acceptance criterion of a similarity of >=98% to sequences in the database. The species distribution between clinical and environmental isolates varied. For the former, four species were detected, with Legionella bozemanae and Legionella micdadei predominating (both 44%). For the latter, eight species were detected, with Legionella anisa predominating (52%). The distribution among the Danish clinical isolates was different from the general distribution both in Europe and outside Europe, where L. bozemanae and Legionella longbeachae are the most commonly found clinical Legionella non-pneumophila species. The 75 isolates were also investigated by matrix-assisted laser desorption ionization time-of flight mass spectrometry (MALDI-TOF MS): 64 were correctly identified, with a score of >=2.0; eight had a score of <2.0, but only two of these were wrongly identified; and three gave no results with MALDI-TOF MS. Both mip sequencing and MALDI-TOF MS are robust methods for Legionella species identification. PMID- 22070606 TI - Differential hypothalamic secretion of neurocrines in male common marmosets: parental experience effects? AB - Pregnancy and lactation produce a plethora of hormonal changes in females that promote maternal care of offspring. Males in the biparental marmoset species (Callithrix jacchus) demonstrate high levels of parenting behaviour and express enhanced circulating reproductive hormones. Furthermore, these hormonal changes are influenced by paternal experience. To determine whether the paternally experienced male marmoset has altered neurocrine hypothalamic release, as the maternal females does, we examined the release of several reproductive neurocrines, dopamine (DA), oxytocin (OT), vasopressin (AVP) and prolactin (PRL), in cultured explants of the hypothalamus of paternally experienced male marmosets compared to naive, paternally inexperienced males. DA levels secreted from the isolated hypothalamus were significantly lower in the experienced males, whereas OT and PRL levels were significantly higher than levels found in inexperienced males. PRL levels decreased rapidly in the hypothalamic media, suggesting that PRL production occurs elsewhere. AVP levels did not change. Stimulation of the cultured explants with oestradiol significantly decreased DA levels in the inexperienced males but did not alter the other neurocrines, suggesting a direct effect of oestradiol on DA suppression in the hypothalamus. Although other factors such as age and rearing experience with siblings may play a role in hypothalamic neurocrine levels, these results demonstrate that paternal experience may impact upon the secretion of neurocrines in a male biparental primate. PMID- 22070607 TI - Cold acclimation induces rapid and dynamic changes in freeze tolerance mechanisms in the cryophile Deschampsia antarctica E. Desv. AB - The cryophilic Antarctic hair grass, Deschampsia antarctica E. Desv., one of two higher plants indigenous to Antarctica, represents a unique resource for the study of freeze tolerance mechanisms. We have previously characterized a multi gene family in D. antarctica encoding ice recrystallization inhibition proteins (IRIPs) whose transcript levels are responsive to cold acclimation, and whose products confer ice recrystallization inhibition (RI) activity that can account for activity seen in cold acclimated plants. We used molecular and physiological analyses to investigate temporal responses of D. antarctica to cold acclimation and de-acclimation, and sub-zero acclimation. Quantitative profiling revealed that IRIP transcript levels significantly increased and decreased within hours of cold acclimation and de-acclimation, respectively, becoming up to 1000-fold more abundant in fully acclimated plants. Western analysis detected three major immuno reactive bands whose pattern of accumulation mirrored that of transcript. These data correlated with the onset and decline of RI activity in acclimated and de acclimated leaves. Plant survival-based testing revealed that cold acclimation enhanced freeze tolerance by 5 degrees C within 4 d, and that sub-zero acclimation conferred an additional 3 degrees C of tolerance. Thus, D. antarctica is highly responsive to temperature fluctuations, able to rapidly deploy IRIP based RI activity and enhance its freeze tolerance. PMID- 22070608 TI - The future of regenerative medicine: urinary system. AB - Regeneration of tissues and organs is now within the technological reach of modern medicine. With such advancements, substantial improvements to existing standards-of-care are very real possibilities. This review will focus on regenerative medicine approaches to treating specific maladies of the bladder and kidney, including the biological basis of regeneration and the history of regenerative medicine in the urinary system. Current clinical management approaches will be presented within the context of future directions including cell-based regenerative therapies. PMID- 22070610 TI - Stem cell challenges in the treatment of neurodegenerative disease. AB - Neurodegenerative diseases result from the gradual and progressive loss of neural cells and lead to nervous system dysfunction. The rapidly advancing stem cell field is providing attractive alternative options for fighting these diseases. Results have provided proof of principle that cell replacement can work in humans with Parkinson's disease (PD). However, three clinical studies of cell transplantation were published that found no net benefit, while patients in two of the studies developed dyskinesias that persisted despite reductions in treatment. Induced pluripotent stem cells (iPSC) have major potential advantages because patient-specific neuroblasts are suitable for transplantation, avoid immune reactions, and can be produced without the use of human ES cells (hESC). Although iPSCs have not been successfully used in clinical trials for PD, patients with amyotrophic lateral sclerosis (ALS) were treated with autologous stem cells and, though they had some degree of decline one year after treatment, they were still improved compared with the preoperative period or without any drug therapy. In addition, neural stem cells (NSCs), via brain-derived neurotrophic factor (BDNF), have been shown to ameliorate complex behavioral deficits associated with widespread Alzheimer's disease (AD) pathology in a transgenic mouse model of AD. So far, the FDA lists 18 clinical trials treating multiple sclerosis (MS), but most are in preliminary stages. This article serves as an overview of recent studies in stem cell and regenerative approaches to the above chronic neurodegenerative disorders. There are still many obstacles to the use of stem cells as a cure for neurodegenerative disease, especially because we still don't fully understand the true mechanisms of these diseases. However, there is hope in the potential of stem cells to help us learn and understand a great deal more about the mechanisms underlying these devastating neurodegenerative diseases. PMID- 22070611 TI - Refractoriness in bipolar disorder: definitions and evidence-based treatment. AB - Defining refractoriness in bipolar disorder is complex and should concern and include either every phase and pole or the disorder as a whole. The data on the treatment of refractory bipolar patients are sparse. Combination and add-on studies suggest that in acutely manic patients partial responders to lithium, valproate, or carbamazepine, a good strategy would be to add haloperidol, risperidone, olanzapine, quetiapine, or aripiprazole. Adding oxcarbazepine to lithium is also a choice. There are no reliable data concerning the treatment of refractory bipolar depressives and also there is no compelling data for the maintenance treatment of refractory patients. It seems that patients stabilized on combination treatment might do worse if shifted from combination. Conclusively there are only limited and sometimes confusing data on the treatment of refractory bipolar patients. Further focused research is necessary on this group of patients. PMID- 22070609 TI - A systematic review of behavioral and treatment outcome studies among HIV infected men who have sex with men who abuse crystal methamphetamine. AB - Men who have sex with men (MSM) have the highest incidence of HIV infection in the United States. One of the contributing factors to HIV spread among this group is the use of crystal methamphetamine ("meth"). The objective was to review the behavioral impact of crystal meth use in HIV-infected MSM and potential treatment options. A systematic review of MEDLINE identified studies that evaluated the clinical effects of crystal meth on the HIV-infected MSM population. Search terms included HIV, methamphetamine, MSM, antiretroviral therapy, adherence, resistance, and treatment. U.S. citations in the English language in peer reviewed journals until December 2010 were included. The primary author reviewed eligible articles, and relevant data including study design, sample, and outcomes were entered into an electronic data table. The 61 included studies highlight that HIV-infected MSM who use crystal meth are more likely to report high-risk sexual behaviors, incident sexually transmitted infections, and serodiscordant unprotected anal intercourse, compared to HIV-infected MSM who do not use crystal meth. Medication adherence in this population is notably low, which may contribute to transmission of resistant virus. No medications have proven effective in the treatment of crystal meth addiction, and the role of behavioral therapies, such as contingency management are still in question. HIV-infected MSM who abuse crystal meth have worse HIV-related health outcomes. Behavioral interventions have shown variable results in treating crystal meth addiction, and more investigation into rehabilitation options are needed. The results presented support efforts to develop and implement novel interventions to reduce crystal meth use in HIV-infected MSM. PMID- 22070612 TI - Pure non-gestational ovarian choriocarcinoma in a 45,XO/46,XX SRY-negative true hermaphrodite. AB - Non-gestational ovarian choriocarcinoma (NGCO) is an extremely rare malignant tumor with a poor prognosis and is difficult to distinguish from gestational choriocarcinoma. True hermaphrodite (TH) is genetically a heterogenous condition causing ovarian and testicular tissue development in the same individual. We report here the first case of pure NGCO in the right ovotestis of a 23-year-old 45,XO/46X,X sex-determining region Y chromosome (SRY)-negative TH. The diagnosis of non-gestational origin was confirmed by testing five short tandem repeats (STR). The patient responded well to radical surgery with bleomycin, etoposide, cisplatin (BEP) regimen. We also hypothesize that some mutations of an X-linked or autosomal gene lead to testicular determination in SRY-negative TH patients. PMID- 22070613 TI - More than meets the eye. Feminist poststructuralism as a lens towards understanding obesity. AB - AIM: This paper presents a discussion of the application of a feminist poststructuralist-based theoretical framework as an innovative approach towards understanding and managing the complex health issue of obesity. BACKGROUND: Obesity is often viewed as a lifestyle choice for which the individual is blamed. This individualistic, dichotomous and behavioural perspective only allows for a narrow understanding of obesity and may even lead to misperceptions, stereotypes and marginalization of clients experiencing obesity. Feminist poststructuralism can provide a critical lens to understand the social construction of obesity and the broader environmental and cultural contexts of this health issue. DATA SOURCES: The theoretical framework draws from the writings of Foucault, Scott, Butler, Cheek, and Powers, published between 1983 and 2005. DISCUSSION: The concepts of discourse analysis and power relations are explored and discussed in a clear manner so that nurses can easily apply this framework to their practice as they observe, question, analyse, critique and assess the care experienced by clients who are obese. The concepts of personal and social beliefs, values and stereotypes are also discussed and examples of how to apply them in practice are provided. IMPLICATIONS: It is imperative that we continue to question our everyday nursing practices as we work to support clients, especially those who feel marginalized. This focus on power relations and reflective practice can give direction to new possibilities for change in obesity management. PMID- 22070614 TI - Antitumor efficacy of photodynamic therapy using novel nanoformulations of hypocrellin photosensitizer SL052. AB - Recent preclinical and clinical testing of hypocrellin-based photosensitizer SL052 for use in photodynamic therapy (PDT) of cancer has shown encouraging results. Further optimization of its formulation for delivery could considerably extend the therapeutic efficiency of this drug. A nanoformulation encapsulating SL052 into biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) was developed using a single-emulsion solvent evaporation technique and characterized in terms of particle size and loading of the photosensitizing agent. This nanoformulation, SL052-PLGA-nanoparticles (NPs), was compared with recently created nanoformulation based on polyvinylpyrrolidone (SL052-PVP-NPs) and standard liposomal SL052 preparation in terms of efficacy when used for PDT treatment of squamous cell carcinomas SCCVII growing subcutaneously in syngeneic mice. The therapeutic effect of PDT using these three different SL052 formulations was tested for both 1 and 4 h intervals between drug injection and tumor light exposure. The longer time interval produced higher tumor cure rates with all SL052 preparations. With both drug-light intervals, PDT based on SL052 PLGA-NPs produced superior therapeutic benefit compared with the other two SL052 formulations. PMID- 22070615 TI - Mode of delivery and other pregnancy outcomes of patients with documented scoliosis. AB - The aim of this study was to explore whether scoliosis is a risk factor for adverse obstetric outcomes and specifically for cesarean delivery (CD) and labor dystocia. Association between scoliosis and pregnancy outcome was studied before. Confounding conclusions prevent proper counseling of patients. Appropriate statistical analysis of a suitable cohort is helpful in resolving this issue. A retrospective population-based study comparing all singleton pregnancies of women with and without documented scoliosis was conducted. Deliveries occurred between the years 1988 and 2009. Multiple logistic regression models were used to control for confounders. Out of 229,116 patients which were included in our cohort, 0.043% (n = 98) had a documented scoliosis. These patients had higher rates of fertility treatments (7.1% vs. 1.6%; p < 0.001). Scoliosis was found to be significantly associated with labor induction (36.7% vs. 26.3 %; p = 0.02) and cesarean deliveries (21.4% vs. 13.1%; p = 0.014). Using multiple logistic regression models, with CD as the outcome variable, controlling for confounders such as nulliparity, labor induction and maternal age, scoliosis was not found to be an independent risk factor for CD (OR = 1.56, 95% CI 1.9-2.7; p = 0.121). Scoliosis is not a risk factor for adverse pregnancy outcome, and specifically for labor dystocia. PMID- 22070616 TI - Reversed-polarity synthesis of diaryl ketones via palladium-catalyzed cross coupling of acylsilanes. AB - Acylsilanes serve as acyl anion equivalents in a palladium-catalyzed cross coupling reaction with aryl bromides to give unsymmetrical diaryl ketones. Water plays a unique and crucial activating role in these reactions. High-throughput experimentation techniques provided successful reaction conditions initially involving phosphites as ligands. Ultimately, 1,3,5,7-tetramethyl-6-phenyl-2,4,8 trioxa-6-phosphaadamantane was identified as giving a longer-lived catalyst with higher turnover numbers. Its use, in conjunction with a palladacycle precatalyst, led to optimal reaction rates and yields. Scope and limitations of this novel method are presented along with initial mechanistic insight. PMID- 22070617 TI - Zinc stabilization efficiency of aluminate spinel structure and its leaching behavior. AB - The feasibility of immobilizing zinc in contaminated soil was investigated by observing the role of zinc reacting with aluminum-rich materials under thermal conditions. To observe the process of zinc incorporation, mixtures of ZnO with alumina precursors (gamma-Al(2)O(3) and alpha-Al(2)O(3)) were fired at 750-1450 degrees C. Both precursors crystallochemically incorporated zinc into the ZnAl(2)O(4) spinel structure. The incorporation efficiencies of a 3 h sintering scheme were first quantitatively determined by Rietveld refinement analysis of X ray diffraction data. Different zinc incorporation behavior by these two precursors was revealed, although both resulted in nearly 100% transformation at the highest temperature. Different product microstructures and thermal densification effects were found by observing the sintered products from these two precursors. The leaching performances of ZnO and ZnAl(2)O(4) were compared by a prolonged acid leaching test for 22 d. The leachability analysis pointed to superiority of the ZnAl(2)O(4) structure in stabilizing zinc, suggesting a promising technique for incorporating zinc into the aluminum-rich product. Finally, the sludge collected from water treatment works was calcined and used as an aluminum-rich material to test its ability to stabilize zinc. Successful formation of ZnAl(2)O(4) indicated good potential for employing waterworks sludge to thermally immobilize hazardous metals as a promising waste-to-resource strategy. PMID- 22070618 TI - Growth kinetics of vertically aligned carbon nanotube arrays in clean oxygen-free conditions. AB - Vertically aligned carbon nanotubes (CNTs) are an important technological system, as well as a fascinating system for studying basic principles of nanomaterials synthesis; yet despite continuing efforts for the past decade many important questions about this process remain largely unexplained. We present a series of parametric ethylene chemical vapor deposition growth studies in a "hot-wall" reactor using ultrapure process gases that reveal the fundamental kinetics of the CNT growth. Our data show that the growth rate is proportional to the concentration of the carbon feedstock and monotonically decreases with the concentration of hydrogen gas and that the most important parameter determining the rate of the CNT growth is the production rate of active carbon precursor in the gas phase reaction. The growth termination times obtained with the purified gas mixtures were strikingly insensitive to variations in both hydrogen and ethylene pressures ruling out the carbon encapsulation of the catalyst as the main process termination cause. PMID- 22070619 TI - Caregivers' difficulties in activating long-term mental illness patients with low self-esteem. AB - The aim of the study was to describe psychiatric caregivers' perceptions of self esteem and activities for patients with long-term mental illness. The study design used a qualitative approach, based on an open lifeworld perspective. A total of 13 caregivers at four psychiatric hospital units in a large Swedish city were interviewed about their views on patients' physical activity and/or other pastimes, as well as their self-esteem and its bearing on the patients' well being. According to the caregivers, it is up to the patients themselves to decide what they wish to occupy themselves with. In the same time the caregivers' opinions are that patients have difficulties to occupy themselves. The caregivers believe that patients' disability is based in a lack of self-esteem, commitment and capacity to realize their wishes. The caregivers in this study argue that activities are valuable for self-esteem and physical health of people with long term mental illness. The caregivers consider that it is the patient's responsibility to initiate their needs of activities. This means that the caregivers do not use their knowledge about the importance of activities for the patient's health. Search terms: activity, caregivers, mental illness. PMID- 22070620 TI - No reactivation of hepatitis e virus after kidney retransplantation. PMID- 22070621 TI - Cognition in action: imaging brain/body dynamics in mobile humans. AB - We have recently developed a mobile brain imaging method (MoBI), that allows for simultaneous recording of brain and body dynamics of humans actively behaving in and interacting with their environment. A mobile imaging approach was needed to study cognitive processes that are inherently based on the use of human physical structure to obtain behavioral goals. This review gives examples of the tight coupling between human physical structure with cognitive processing and the role of supraspinal activity during control of human stance and locomotion. Existing brain imaging methods for actively behaving participants are described and new sensor technology allowing for mobile recordings of different behavioral states in humans is introduced. Finally, we review recent work demonstrating the feasibility of a MoBI system that was developed at the Swartz Center for Computational Neuroscience at the University of California, San Diego, demonstrating the range of behavior that can be investigated with this method. PMID- 22070622 TI - Factors associated with parenting behavior of mothers in the early postpartum period in Turkey. AB - This study determined the factors associated with parenting behavior during the early postpartum period in first-time mothers. This cross-sectional, descriptive study was conducted in the postpartum ward of a state hospital in Aydin, Turkey. The study included 207 first-time mothers selected by non-probability sampling method. A significant weak, positive correlation was found between the Postpartum Parenting Behavior Scale score at the time of initial acquaintance with her infant and the Labor Agentry Scale score. Stepwise multiple regression analyses, performed to determine factors associated with the parenting behavior score of the mothers in the early postpartum period, revealed two statistically significant variables, which increased the strength of the model: maternal age and infant's birth weight. Midwives should observe early parenting behaviors, particularly of younger mothers having babies with low birth weight, appreciate their positive behaviors, and encourage them to develop appropriate behavior. PMID- 22070623 TI - Clinical characteristics and favorable long-term outcomes for patients with idiopathic inflammatory myopathies: a retrospective single center study in China. AB - BACKGROUND: Little is known about the clinical features and true survival risk factors in Chinese Han population. We conducted the current study to investigate the clinical features, long-term outcome and true potential indicators associated with mortality of idiopathic inflammatory myopathies (IIM) in China. METHODS: We restrospectvely investigated 188 patients diagnosed with IIM at our hospital from January 1986 to April 2009. The primary outcome was determined with mortality. The secondary outcomes for survival patients were organ damage and disease activity, health status, and disability, which were assessed with Myositis Damage Index, Myositis Disease Activity Assessment Visual Analogue Scales, Health Assessment Questionnaire Disability Index, and the Modified Rankin Scale, respectively. Potential prognostic factors for mortality were analyzed with the multivariate Cox regression model. RESULTS: Mean age at disease onset was 43.8 +/ 15.8 years and male to female ratio was 1:2.1 in this cohort. The 1-, 5-, 10-, 15- and 20-year survival rates were 93.6%, 88.7%, 81%, 73.6% and 65.6%. The independent predicators for mortality were age at disease onset [hazard ratio (HR):1.05, 95% CI 1.02 - 1.08], presence of cancer (HR:3.68, 95%CI 1.39 - 9.74), and elevated IgA level at diagnosis (HR:2.80, 95% CI 1.16-6.74). At the end of the follow-up, 29 patients manifested drug withdrawal within an average 4.1 years (range 0.5-15.2 year), most patients (85.9%) had no disease activity and 130 patients (83.4%) had no disability. CONCLUSIONS: The long-term outcomes of IIM patients in our cohort have improved dramatically. Those patients most likely to survive had a high chance of reaching stable disease status, and obtained long term or possibly permanent remission to a large extent. PMID- 22070624 TI - Rising epidemic of diabetes and hypertension in Asia. PMID- 22070625 TI - Developmental changes in mesophyll diffusion conductance and photosynthetic capacity under different light and water availabilities in Populus tremula: how structure constrains function. AB - Finite mesophyll diffusion conductance (g(m) ) significantly constrains net assimilation rate (A(n) ), but g(m) variations and variation sources in response to environmental stresses during leaf development are imperfectly known. The combined effects of light and water limitations on g(m) and diffusion limitations of photosynthesis were studied in saplings of Populus tremula L. An one-dimensional diffusion model was used to gain insight into the importance of key anatomical traits in determining g(m) . Leaf development was associated with increases in dry mass per unit area, thickness, density, exposed mesophyll (S(mes) /S) and chloroplast (S(c) /S) to leaf area ratio, internal air space (f(ias) ), cell wall thickness and chloroplast dimensions. Development of S(mes) /S and S(c) /S was delayed under low light. Reduction in light availability was associated with lower S(c) /S, but with larger f(ias) and chloroplast thickness. Water stress reduced S(c) /S and increased cell wall thickness under high light. In all treatments, g(m) and A(n) increased and CO(2) drawdown because of g(m) , C(i) -C(c) , decreased with increasing leaf age. Low light and drought resulted in reduced g(m) and A(n) and increased C(i) -C(c) . These results emphasize the importance of g(m) and its components in determining A(n) variations during leaf development and in response to stress. PMID- 22070626 TI - Dental developmental disturbances in 50 individuals with the 22q11.2 deletion syndrome; relation to medical conditions? AB - OBJECTIVE: The aims of the study were to examine tooth and enamel disturbances in individuals with 22q11.2 deletion syndrome and to analyze associations with medical conditions, birth characteristics and blood values of calcium and PTH. MATERIALS AND METHODS: Fifty individuals participated in the study (27 females, median age 10 years, range 1.5-44). Congenital absence of teeth was studied on orthopantomograms; 1148 teeth were examined, both clinically and radiologically, and enamel hypomineralizations and hypoplasias were recorded. Medical history and findings were recorded as part of a larger study on the manifestations of 22q11.2 deletion syndrome in Norway. RESULTS: Tooth agenesis was observed in 15% of study participants. Sixty-six percent of the participants and 26.0% of teeth presented with enamel disturbances. Of these, 12 individuals (24.0%) and 215 teeth (18.7%) had hypomineralizations and four individuals (8.0%) and 86 teeth (7.5%) had hypoplasias. Seventeen participants (34.0%) presented with both types of disturbance, but rarely in the same tooth. Only two teeth (0.17%) had both types of disturbance. Hypomineralizations were twice as frequent in permanent as in primary teeth. No correlations were found to medical conditions, except that participants with congenital cardiac anomalies presented with fewer total enamel disturbances and hypomineralizations in permanent teeth than those without. CONCLUSIONS: Enamel disturbances were frequently seen. There were more hypomineralizations than hypoplasias. Hypoparathyroidism and/or hypocalcemia are not clear etiological factors for enamel disturbances and there were no major correlations between medical conditions and enamel disturbances. PMID- 22070627 TI - Bifunctional MU/delta opioid peptides: variation of the type and length of the linker connecting the two components. AB - On the basis of evidence that opioid compounds with a mixed MU agonist/delta antagonist profile may produce an antinociceptive effect with low propensity to induce side effects, bifunctional opioid peptides containing the MU agonist H-Dmt d-Arg-Phe-Lys-NH(2) ([Dmt(1) ]DALDA; Dmt = 2',6'-dimethyltyrosine) connected tail to-tail via various alpha,omega-diaminoalkyl- or diaminocyclohexane linkers to the delta antagonists H-Tyr-TicPsi[CH(2) -NH]Cha-Phe-OH (TICP[Psi]; Cha = cyclohexylalanine, Tic = 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid), H-Dmt Tic-OH or H-Bcp-Tic-OH (Bcp = 4'-[N-((4' phenyl)phenethyl)carboxamido]phenylalanine) were synthesized and pharmacologically characterized in vitro. Bifunctional [Dmt(1) ]DALDA->NH-(CH(2) )(n) -NH<-TICP[Psi] compounds (n = -12) showed decreasing MU and delta receptor binding affinities with increasing linker length. As expected, several of the bifunctional peptides were MU agonist/delta antagonists with low nanomolar MU and delta receptor binding affinities. However, compounds with unexpected opioid activity profiles, including a MU partial agonist/delta partial agonist, MU antagonist/delta antagonists and MU agonist/delta agonists, were also identified. These results indicate that the binding affinities and intrinsic efficacies of these bifunctional compounds at both receptors depend on the length and type of the linker connecting the MU and delta components. An important recommendation emerging from this study is that the in vitro activity profiles of bifunctional compounds containing an agonist and an antagonist component connected via a linker need to be determined prior to their pharmacological evaluation in vivo. PMID- 22070628 TI - 'I think we're all guinea pigs really': a qualitative study of medication and borderline personality disorder. AB - National Institute for Clinical Excellence recommended the use of medication only in times of crisis for individuals with borderline personality disorder (BPD). Despite this recommendation most service users referred to a specialist personality disorder service were found to be on numerous medications. Although a number of qualitative studies have explored the experience of individuals with a diagnosis of BPD they have failed to discuss their experience of being treated with medication, despite its high prescription with this group (e.g. Sansone et al.). The aim of this study was to explore the experience of service users being treated with medication for the BPD diagnosis. Semi-structured interviews were carried out with seven service users under a specialist service for personality disorder. Interviews were transcribed and analysed using thematic analysis. The main themes to emerge were: staff knowledge and attitudes, lack of resources for BPD and the recovery pathway for BPD. Overall, service users felt that receiving the BPD diagnosis had had a negative impact on the care they received, with staff either refusing treatment or focusing on medication as a treatment option. The introduction of specialist services for this group appears to improve service user satisfaction with their treatment and adherence to the National Institute for Clinical Excellence guidelines. PMID- 22070629 TI - Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905). AB - This article describes the discovery of a series of potent inhibitors of Polo like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model. PMID- 22070631 TI - The treatment of 'difficult' patients in a secure unit of a specialized psychiatric hospital: the patient's perspective. AB - The aim of this study is to obtain insight, from a patient's perspective, into the results and essential components of treatment in specialist settings for so called 'difficult' patients in mental health care. In cases where usual hospital treatment is not successful, a temporary transfer to another, specialist hospital may provide a solution. We investigated which aspects of specialist treatment available to 'difficult' patients are perceived as essential by the patients and what are the results of this treatment in their perception. A qualitative research design based on the Grounded Theory method was used. To generate data, 14 semi-structured interviews were held with 12 patients who were admitted to a specialist hospital in the Netherlands. Almost all respondents rated the results of the specialist treatment as positive. The therapeutic climate was perceived as extremely strict, with a strong focus on structure, cooperation and safety. This approach had a stabilizing effect on the patients, even at times when they were not motivated. Most patients developed a motivation for change, marked by a growing and more explicit determination of their future goals. We concluded that a highly structured treatment environment aimed at patient stabilization is helpful to most 'difficult' patients. PMID- 22070630 TI - A randomised trial comparing the laryngeal mask airway SupremeTM with the laryngeal mask airway UniqueTM in children. AB - We conducted a randomised controlled trial comparing the laryngeal mask airway Supreme(TM) with the laryngeal mask airway Unique(TM) in children. Fifty children presenting for elective surgery were randomly assigned to receive either the laryngeal mask airway Supreme or laryngeal mask airway Unique. The outcomes measured were airway leak pressure, ease and time for insertion, insertion success rate, fibreoptic examination, incidence of gastric insufflation, ease of gastric tube placement through the laryngeal mask airway Supreme, quality of airway during anaesthetic maintenance and complications. Median (IQR [range]) time to successful device placement was shorter with the laryngeal mask airway Unique, 14.5 [13.5-16.3 (10.0-23.6)] s than with the laryngeal mask airway Supreme, 17.4 [14.8-19.8 (11.5-29.2)] s; p = 0.007. Median (IQR [range]) airway leak pressures for the laryngeal mask airway Supreme and laryngeal mask airway Unique were 20 [16-21 (12-22)] cmH(2)O and 15 [14-18 (10-24)] cmH(2)O, respectively (p = 0.001). The incidence of gastric insufflation was lower with the laryngeal mask airway Supreme (zero vs six patients), p = 0.01. In conclusion, the laryngeal mask airway Supreme performed as well as the laryngeal mask airway Unique and is a useful alternative for airway maintenance, particularly in children who require evacuation of gastric contents during anaesthesia. PMID- 22070633 TI - Asymmetric intramolecular cyclobutane formation via photochemical reaction of N,N diallyl-2-quinolone-3-carboxamide using a chiral crystalline environment. AB - Crystal structures and photochemical reactions of three N,N-diallyl-2-quinolone-3 carboxamides were investigated. One quinolonecarboxamide afforded chiral crystals of a P2(1) crystal system by spontaneous crystallization, and the molecular chirality in the crystal was effectively transferred to cyclobutane in 96% ee by an intramolecular 2 + 2 photocycloaddition reaction in the solid state. PMID- 22070632 TI - Generation of human adult mesenchymal stromal/stem cells expressing defined xenogenic vascular endothelial growth factor levels by optimized transduction and flow cytometry purification. AB - Adult mesenchymal stromal/stem cells (MSCs) are a valuable source of multipotent progenitors for tissue engineering and regenerative medicine, but may require to be genetically modified to widen their efficacy in therapeutic applications. For example, overexpression of the angiogenic factor vascular endothelial growth factor (VEGF) at controlled levels is an attractive strategy to overcome the crucial bottleneck of graft vascularization and to avoid aberrant vascular growth. Since the regenerative potential of MSCs is rapidly lost during in vitro expansion, we sought to develop an optimized technique to achieve high-efficiency retroviral vector transduction of MSCs derived from both adipose tissue (adipose stromal cells, ASCs) or bone marrow (BMSCs) and rapidly select cells expressing desired levels of VEGF with minimal in vitro expansion. The proliferative peak of freshly isolated human ASCs and BMSCs was reached 4 and 6 days after plating, respectively. By performing retroviral vector transduction at this time point, >90% efficiency was routinely achieved before the first passage. MSCs were transduced with vectors expressing rat VEGF(164) quantitatively linked to a syngenic cell surface marker (truncated rat CD8). Retroviral transduction and VEGF expression did not affect MSC phenotype nor impair their in vitro proliferation and differentiation potential. Transgene expression was also maintained during in vitro differentiation. Furthermore, three subpopulations of transduced BMSCs homogeneously producing specific low, medium, and high VEGF doses could be prospectively isolated by flow cytometry based on the intensity of their CD8 expression already at the first passage. In conclusion, this optimized platform allowed the generation of populations of genetically modified MSCs, expressing specific levels of a therapeutic transgene, already at the first passage, thereby minimizing in vitro expansion and loss of regenerative potential. PMID- 22070634 TI - Experimental hypothyroidism delays field excitatory post-synaptic potentials and disrupts hippocampal long-term potentiation in the dentate gyrus of hippocampal formation and Y-maze performance in adult rats. AB - Manipulations of thyroid hormones have been shown to influence learning and memory. Although a large body of literature is available on the effect of thyroid hormone deficiency on learning and memory functions during the developmental stage, electrophysiological and behavioural findings, particularly on propylthiouracil administration to adult normothyroid animals, are not satisfactory. The experiments in the present study were carried out on 12 adult male Wistar rats aged 6-7 months. Hypothyroidism was induced by administering 6-n propyl-2-thiouracil in their drinking water for 21 days at a concentration of 0.05%. The spatial learning performance of hypothyroid and control rats was studied on a Y-maze. The rats were then placed in a stereotaxic frame under urethane anaesthesia. A bipolar tungsten electrode was used to stimulate the medial perforant path. A glass micropipette was inserted into the granule cell layer of the ipsilateral dentate gyrus to record field excitatory post-synaptic potentials. After a 15-min baseline recording of field potentials, long-term potentiation was induced by four sets of tetanic trains. The propylthiouracil treated rats showed a significantly attenuated input-output (I/O) relationship when population spike (PS) amplitudes and field excitatory post-synaptic potentials (fEPSP) were compared. fEPSP and PS latencies were found to be longer in the hypothyroid group than in the control group. The PS amplitude and fEPSP slope potentiations in the hypothyroid rats were not statistically different from those in the control rats, except for the field EPSP slope measured in the post tetanic and maintenance phases. The hypothyroid rats also showed lower thyroxine levels and poor performance in the spatial memory task. The present study provides in vivo evidence for the action of propylthiouracil leading to impaired synaptic plasticity, which might explain deficit in spatial memory tasks in adult hypothyroid rats. PMID- 22070635 TI - Rationale for control of anthropogenic nitrogen and phosphorus to reduce eutrophication of inland waters. AB - Concentrations of phosphorus and nitrogen in surface waters are being regulated in the United States and European Union. Human activity has raised the concentrations of these nutrients, leading to eutrophication of inland waters, which causes nuisance growth of algae and other aquatic plants. Control of phosphorus often has had the highest priority because of its presumed leading role in limiting development of aquatic plant biomass. Experimental evidence shows, however, that nitrogen is equally likely to limit growth of algae and aquatic plants in inland waters, and that additions of both nutrients cause substantially more algal growth than either added alone. A dual control strategy for N and P will reduce transport of anthropogenic nitrogen through drainage networks to aquatic ecosystems that may be nitrogen limited. Control of total phosphorus in effluents is feasible and is increasingly being required by regulations. The control strategy for nitrogen in effluents is more difficult, but could be made more feasible by recognition that a substantial portion of dissolved organic nitrogen is not bioavailable; regulation should focus on bioavailable N (nitrate, ammonium, and some dissolved organic nitrogen) rather than total N. Regulation of both N and P also is essential for nonpoint sources. PMID- 22070636 TI - Metabolic syndrome and bipolar disorder: what should psychiatrists know? AB - This paper reviews the association between bipolar disorder (BD) and metabolic syndrome (MetS), focusing on the etiopathogenetic and pathophysiological aspects of this association and on the recommendations for preventing and managing MetS in patients with BD. We conducted a nonsystematic literature review by means of a MEDLINE search. The exact causal relationship between MetS and BD is still uncertain. The side effects of psychotropic medications may be a major contributor to the increased rates of MetS in patients with BD. Other factors such as unhealthy lifestyles, common neuroendocrine and immuno-inflammatory abnormalities, and genetic vulnerability may also play a role in explaining the high rates of MetS in BD. Strategies to prevent and treat the MetS and its cardiovascular consequences in patients with BD include accurate screening and monitoring of the patient and appropriate psychoeducation on weight control, healthy nutrition, and increased physical activity. When deciding on pharmacological therapy for the treatment of the components of the MetS, drug interactions and the effects of the medications on mood must be taken into account. PMID- 22070637 TI - Evolving epidemiology of invasive Haemophilus infections in the post-vaccination era: results from a long-term population-based study. AB - Historically, Haemophilus influenzae (Hi) serotype b (Hib) caused most invasive Haemophilus infections worldwide, mainly in children. In 1989 routine childhood vaccination against Hib was initiated in Iceland. We conducted a population-based study of all patients in the country with Haemophilus spp. isolated from sterile sites (n = 202), from 1983 to 2008. Epidemiology, clinical characteristics of the infections and serotypes of the isolates were compared during the pre-vaccination (1983-1989) and post-vaccination era (1990-2008). Following the vaccination, the overall incidence of Hib decreased from 6.4 to 0.3/100,000 per year (p <0.05) whereas the incidence did not change significantly for infections caused by Haemophilus sensu lato not serotype b, hereafter referred to as non-type b Hi (0.9 vs 1.2, respectively). The most frequent diagnosis prior to 1990 was meningitis caused by Hib, which was subsequently replaced by pneumonia and bacteraemia caused by non-type b Hi. Most commonly, non-type b Hi were non typeable (NTHi; 40/59), followed by Hi serotype f (14/59) and Hi serotype a (3/59). Pregnancy was associated with a markedly increased susceptibility to invasive Haemophilus infections (RR 25.7; 95% CI 8.0-95.9, p <0.0001) compared with non-pregnant women. The case fatality rate for Hib was 2.4% but 14% for non type b Hi, highest at the extremes of age. Hib vaccination gives young children excellent protection and decreases incidence in the elderly due to herd effect in the community. Replacement with other species or serotypes has not been noted. Pregnant women are an overlooked risk group. PMID- 22070638 TI - Hemodynamic responses to a hemoglobin bis-tetramer and its polyethylene glycol conjugate. AB - BACKGROUND: The design of hemoglobin-based oxygen carriers (HBOCs) poses a significant challenge as clinical trials of many materials have reported adverse side effects that may come from the scavenging of the vasodilator nitric oxide (NO). A compensating reaction, reduction of endogenous nitrite by hemoglobin (Hb) and its derivatives, generates NO. Polyethylene glycol (PEG) conjugation of Hb enhances the rate of the reaction. STUDY DESIGN AND METHODS: Hemoglobin bis tetramers (BT) and their PEGylated derivative (BT-PEG) bind oxygen with a degree of cooperativity and also have significantly enhanced nitrite reductase activity compared to the native protein. Circulatory evaluation will test if the properties of BT and BT-PEG are reflected in their effects in vivo. BT and BT-PEG were evaluated as infusions into healthy wild-type (WT) and diabetic (db/db) mouse models. The effects were compared to infusions of murine Hb. RESULTS: The materials were found not to cause significant increases in systemic blood pressure in either WT mice or db/db mice. The latter are highly sensitive to NO scavenging. Further hemodynamic measurements in WT mice indicate that while a slight increase in systemic vascular resistance (SVR) was observed after infusion of BT, the extent is not significant. No change in SVR from baseline was observed after infusion of BT-PEG. CONCLUSION: The enlarged Hb derivatives do not evoke unfavorable circulatory responses that have been noted to result from infusion of Hb derivatives. These results suggest that a compromise between the P(50) , n(50) , and nitrite reductase activity of a Hb derivative can serve as the basis for producing HBOCs that can be tested for vasoactivity. PMID- 22070639 TI - Energetics and mechanisms for the unimolecular dissociation of protonated trioses and relationship to proton-mediated formaldehyde polymerization to carbohydrates in interstellar environments. AB - We report the unimolecular decomposition of protonated glyceraldehyde, [HOCH(2)CH(OH)CHO]H(+), and protonated dihydroxyacetone, [HOCH(2)C(O)CH(2)OH]H(+). On the basis of mass spectrometric experiments and computational quantum chemistry, we have found that these isomeric ions interconvert freely at energies below that required for their unimolecular decompositions. The losses of formaldehyde and water (the latter also followed by CO loss) are the dominating processes, with formaldehyde loss having the lower energetic threshold. The reverse of the formaldehyde loss, namely, the addition of formaldehyde to protonated glycolaldehyde, appears to be an inefficient reaction at low temperature and pressure in the gas phase, leading to dissociation products. The relevance of these findings to interstellar chemistry and prebiotic chemistry is discussed, and it is concluded that the suggestion made in the literature that successive addition of formaldehyde by proton assisted reactions should account for interstellar carbohydrates most likely is incorrect. PMID- 22070640 TI - NK cells: new partners in antibody-triggered chronic rejection. PMID- 22070641 TI - Interval and continuous exercise elicit equivalent postexercise hypotension in prehypertensive men, despite differences in regulation. AB - Equicaloric bouts of interval (IE: 5 * 2:2 min at 85% and 40% maximal oxygen uptake) and steady state (SS: 21 min at 60% maximal oxygen uptake) exercise were performed by 13 older prehypertensive males on separate days, at equivalent times of day, to assess the influence of exercise mode on postexercise hypotension (PEH). Exercise conditions were compared with a control session. Cardiovascular measures were collected for 30 min prior to, and 60 min following exercise. PEH, as measured by mean postexercise systolic blood pressure (SBP) decrease (IE: -4 +/- 6 mm Hg; SS: -3 +/- 4 mm Hg; control: 4 +/- 4 mm Hg), area under the SBP curve (IE: -240 +/- 353 mm Hg.min; SS: -192 +/- 244 mm Hg.min), and minimum SBP achieved (IE: -15 +/- 7 mm Hg; SS: -13 +/- 7 mm Hg), was equivalent after both conditions. Stroke volume was significantly reduced (IE: -14.6 +/- 16.0 mL; SS: 10.1 +/- 14.2 mL, control -1.7 +/- 2.2 mL) and heart rate was significantly elevated (IE: 13 +/- 8 beats.min-1; SS: 7.9 +/- 8 beats.min-1; control: -2 +/- 3 beats.min-1) postexercise after both conditions. Cardiac output and total peripheral resistance were nonsignificantly decreased and increased postexercise, respectively. Baroreflex sensitivity (BRS) was reduced following IE (p < 0.05) and heart rate variability (HRV) parameters were reduced after both conditions, with IE eliciting larger and longer reductions in some indices. The results from the current study indicate that older prehypertensive adults experience similar PEH following equicaloric bouts of IE and SS exercise despite larger alterations in HRV and BRS elicited by IE. PMID- 22070642 TI - Lithium: still a major option in the management of bipolar disorder. AB - Still after more than 50 years, lithium is a major treatment of bipolar disorder, even though it has not been promoted by the pharmaceutical industry over the last decades. In recent years the evidence base on lithium for bipolar disorder has substantially increased due to results from a number of trials. Therefore, a review of this evidence is timely. The efficacy of lithium as an acute treatment and as a maintenance treatment of bipolar disorder was evaluated through a review of the evidence, focusing on modern, randomized, parallel-group designed trials. Additionally, the evidence was sought translated into the proper use of lithium in clinical practice. Lithium's antimanic efficacy has been convincingly demonstrated. However, as blood monitoring due to the risk of toxicity is required and due to an insufficient response in highly agitated patients, lithium monotherapy has a limited place in the acute treatment of severe manic states. For acute bipolar depression, results are conflicting. Recent maintenance trials have added substantially to the documentation of lithium's long-term stabilizing properties in bipolar disorder, and these properties have been demonstrated independently of any acute response to lithium. Finally, it is now beyond doubt that not only does lithium prevent mania, but also depression in bipolar disorder. Lithium is still to be considered a major if not the most important mood- stabilizer, at least for maintaining long-term stability in patients with bipolar disorder. The potential risks of lithium should be weighed up against its benefits and the fact that serious adverse effects are usually avoidable. PMID- 22070643 TI - Interprofessional working or role substitution? A discussion of the emerging roles in emergency care. AB - AIMS: This article presents a discussion of emerging non-medical roles in emergency care against the current policy context and the issues of role substitution and interprofessional working. BACKGROUND: Non-medical roles in emergency care have grown internationally in response to an increasing demand for emergency care services and to address the growing importance of the quality healthcare agenda. The blurring of role boundaries between professional groups has become more common. Data sources. Searches were made of three electronic databases; CINAHL, Medline and EMBASE. The literature relating to interprofessional healthcare roles, and new roles in emergency care was searched from 1980 to 2010 and underpinned the discussion. DISCUSSION: A theoretical framework that has emerged from the literature is that task, role substitution and interprofessional working lie on a spectrum and evolving non-medical roles can be plotted on the spectrum, usually starting at one end of the spectrum under task substitution and then potentially moving in time towards true interprofessional working. CONCLUSIONS: There is still a great deal of progress to be made until non-medical roles in emergency care can truly be encompassed under the umbrella of interprofessional working and that a more robust critical mass of evidence is required to substantiate the theory that interprofessional working within teams contributes to effective, cost-effective care and better patient outcomes. RELEVANCE TO CLINICAL PRACTICE: It is essential to understand the underlying motivation, policy context and key drivers for the development of new nursing and non-medical roles. This allows services to be established successfully, by understanding and addressing the key predicable barriers to implementation and change. PMID- 22070644 TI - Mammary tumors that become independent of the type I insulin-like growth factor receptor express elevated levels of platelet-derived growth factor receptors. AB - BACKGROUND: Targeted therapies are becoming an essential part of breast cancer treatment and agents targeting the type I insulin-like growth factor receptor (IGF-IR) are currently being investigated in clinical trials. One of the limitations of targeted therapies is the development of resistant variants and these variants typically present with unique gene expression patterns and characteristics compared to the original tumor. RESULTS: MTB-IGFIR transgenic mice, with inducible overexpression of the IGF-IR were used to model mammary tumors that develop resistance to IGF-IR targeting agents. IGF-IR independent mammary tumors, previously shown to possess characteristics associated with EMT, were found to express elevated levels of PDGFRalpha and PDGFRbeta. Furthermore, these receptors were shown to be inversely expressed with the IGF-IR in this model. Using cell lines derived from IGF-IR-independent mammary tumors (from MTB IGFIR mice), it was demonstrated that PDGFRalpha and to a lesser extent PDGFRbeta was important for cell migration and invasion as RNAi knockdown of PDGFRalpha alone or PDGFRalpha and PDGFRbeta in combination, significantly decreased tumor cell migration in Boyden chamber assays and suppressed cell migration in scratch wound assays. Somewhat surprisingly, concomitant knockdown of PDGFRalpha and PDGFRbeta resulted in a modest increase in cell proliferation and a decrease in apoptosis. CONCLUSION: During IGF-IR independence, PDGFRs are upregulated and function to enhance tumor cell motility. These results demonstrate a novel interaction between the IGF-IR and PDGFRs and highlight an important, therapeutically relevant pathway, for tumor cell migration and invasion. PMID- 22070645 TI - Heat transfer across the interface between nanoscale solids and gas. AB - When solid materials and devices scale down in size, heat transfer from the active region to the gas environment becomes increasingly significant. We show that the heat transfer coefficient across the solid-gas interface behaves very differently when the size of the solid is reduced to the nanoscale, such as that of a single nanowire. Unlike for macroscopic solids, the coefficient is strongly pressure dependent above ~10 Torr, and at lower pressures it is much higher than predictions of the kinetic gas theory. The heat transfer coefficient was measured between a single, free-standing VO(2) nanowire and surrounding air using laser thermography, where the temperature distribution along the VO(2) nanowire was determined by imaging its domain structure of metal-insulator phase transition. The one-dimensional domain structure along the nanowire results from the balance between heat generation by the focused laser and heat dissipation to the substrate as well as to the surrounding gas, and thus serves as a nanoscale power meter and thermometer. We quantified the heat loss rate across the nanowire-air interface, and found that it dominates over all other heat dissipation channels for small-diameter nanowires near ambient pressure. As the heat transfer across the solid-gas interface is nearly independent of the chemical identity of the solid, the results reveal a general scaling relationship for gaseous heat dissipation from nanostructures of all solid materials, which is applicable to nanoscale electronic and thermal devices exposed to gaseous environments. PMID- 22070646 TI - A specialist root herbivore exploits defensive metabolites to locate nutritious tissues. AB - The most valuable organs of plants are often particularly rich in essential elements, but also very well defended. This creates a dilemma for herbivores that need to maximise energy intake while minimising intoxication. We investigated how the specialist root herbivore Diabrotica virgifera solves this conundrum when feeding on wild and cultivated maize plants. We found that crown roots of maize seedlings were vital for plant development and, in accordance, were rich in nutritious primary metabolites and contained higher amounts of the insecticidal 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and the phenolic compound chlorogenic acid. The generalist herbivores Diabrotica balteata and Spodoptera littoralis were deterred from feeding on crown roots, whereas the specialist D. virgifera preferred and grew best on these tissues. Using a 1,4-benzoxazin-3-one deficient maize mutant, we found that D. virgifera is resistant to DIMBOA and other 1,4-benzoxazin-3-ones and that it even hijacks these compounds to optimally forage for nutritious roots. PMID- 22070647 TI - Combined impacts of irradiance and dehydration on leaf hydraulic conductance: insights into vulnerability and stomatal control. AB - The leaf is a hydraulic bottleneck, accounting for a large part of plant resistance. Thus, the leaf hydraulic conductance (K(leaf) ) is of key importance in determining stomatal conductance (g(s) ) and rates of gas exchange. Previous studies showed that K(leaf) is dynamic with leaf water status and irradiance. For four species, we tested the combined impacts of these factors on K(leaf) and on g(s) . We determined responses of K(leaf) and g(s) to declining leaf water potential (Psi(leaf) ) under low and high irradiance (<6 and >900 umol photons m( 2) s(-1) photosynthetically active radiation, respectively). We hypothesized greater K(leaf) vulnerability under high irradiance. We also hypothesized that K(leaf) and g(s) would be similar in their responses to either light or dehydration: similar light-responses of K(leaf) and g(s) would stabilize Psi(leaf) across irradiances for leaves transpiring at a given vapour pressure deficit, and similar dehydration responses would arise from the control of stomata by Psi(leaf) or a correlated signal. For all four species, the K(leaf) light response declined from full hydration to turgor loss point. The K(leaf) and g(s) differed strongly in their light- and dehydration responses, supporting optimization of hydraulic transport across irradiances, and semi-independent, flexible regulation of liquid and vapour phase water transport with leaf water status. PMID- 22070648 TI - Factors associated with good self-management in older adults with a schizophrenic disorder compared with older adults with physical illnesses. AB - The number of older people living with a schizophrenic disorder (SD) is increasing yet little attention paid has been paid to the needs of this population relative to people with other chronic illnesses. In order to achieve optimal functioning people with a SD need to manage their illness and its impact; therefore, this study set out to determine the factors associated with self management in this population. The illness management of people over 50 years of age and living with schizophrenia (n= 84) was compared with their peers who were diagnosed with a chronic physical illness (n= 216). Participants completed a survey that included an illness management inventory, self-rated health and sense of coherence. The results demonstrated that participants with a SD had lower illness management levels, particularly for understanding their symptoms and taking appropriate actions in relation to health care. Poor self-rated health and the presence of comorbid conditions had a pervasive negative effect on self management factors in the SD group, whereas being married, having a greater sense of coherence and being voluntary to treatment had a positive effect. Nurses need to develop strategies to address general health and self-management in older adults living with a SD. PMID- 22070649 TI - Genetic variation in the NBS1 gene is associated with hepatic cancer risk in a Chinese population. AB - NBS1 plays important roles in maintaining genomic stability as a key DNA repair protein in the homologous recombination repair pathway and as a signal modifier in the intra-S phase checkpoint. We hypothesized that polymorphisms of NBS1 are associated with hepatic cancer (HCC) risk. The NBS1 rs1805794 C/G polymorphism has been frequently studied in some cancers with discordant results, but its association with HCC has not been investigated. Moreover, studies of the 3'UTR variant rs2735383 have not touched upon HCC. This study examined the contribution of these two polymorphisms to the risk of developing HCC in a Chinese population. NBS1 genotypes were determined in 865 HCC patients and 900 controls and the associations with risk of HCC were estimated by logistic regression. Compared with the rs1805794 GG genotype, the GC genotype had a significantly increased risk of HCC (adjusted odds ratios [OR]=1.41; 95% confidence interval [CI]=1.11 1.80), the CC carriers had a further increased risk of HCC (OR=2.27; 95% CI=1.68 3.14), and there was a trend for an allele dose effect on risk of HCC (p<0.001). Also, we found that the risk effect of rs1805794 CC+CG was more pronounced in HCC patients that drank (OR=2.28, 95% CI=1.55-3.29 for drinkers; OR=1.31, 95% CI=1.00 1.77 for nondrinkers). However, there was no significant difference in genotype frequencies of rs2735383 G/C site between cases and controls. These findings suggest that rs1805794 C/G polymorphism in NBS1 may be a genetic modifier for developing HCC. PMID- 22070650 TI - Meta-analysis of epidermal growth factor polymorphisms and cancer risk: involving 9,779 cases and 15,932 controls. AB - The epidermal growth factor (EGF) pathway stimulates proliferation and differentiation of epidermal and epithelial tissues, and plays an important role in tumorigenesis. The association between EGF polymorphisms and cancer risk is controversial; thus, we performed this meta-analysis. Overall, 41 case-control studies with 9,779 cases and 15,932 controls were retrieved. We found that EGF +61A/G polymorphism increased overall cancer risk (G allele vs. A allele: OR=1.181, 95% CI=1.077-1.295, P(heterogeneity) < 0.001; GG vs. AA: OR=1.370, 95% CI=1.143-1.641, P(heterogeneity) < 0.001; GG+GA vs. AA: OR=1.175, 95% CI=1.047 1.318, P(heterogeneity) < 0.001). In the stratified analysis by cancer type, the +61 G allele was a risk factor for colorectal cancer, esophageal carcinoma, gastric cancer, and hepatocellular carcinoma. Individuals who carried +61G allele had higher cancer susceptibility in mixed and European racial subgroups. An increased association was detected in the hospital-based subgroup. No significant association was found among EGF -1380A/G, -1744G/A, rs6983267T/G polymorphisms and cancer risk. PMID- 22070651 TI - Involvement of T2677T multidrug resistance gene polymorphism in Interleukin 22 plasma concentration in B-chronic lymphocytic leukemia patients. PMID- 22070652 TI - Aptitude-based assignment of nurses to depressed patients. AB - In psychiatric units, head nurses face the daily challenge of assigning nurses to patients. The 'match' between a patient and a nurse is not always optimal. This can hinder the therapeutic relationship. Aptitude is an important component of competence, especially for psychiatric nurses involved in therapeutic relationships. In this study, we undertook explorative research to investigate possible relationships between nurse aptitudes and outcomes in depressed patients. We found statistically significant relationships between specific nurse aptitudes, along professional rank, and particular patient outcomes. During the hospital stay, patients' depressive feelings change as they recover. Our results indicate that, as a patient's depressive feelings change, another type of nurse, one with an aptitude that supports the patient's current needs, should be assigned to care for that patient. This suggestion is at odds with current practises of assigning a patient to one nurse for the entire hospital stay. PMID- 22070653 TI - Critical congenital heart disease--utility of routine screening for chromosomal and other extracardiac malformations. AB - Objective. Infants with critical congenital heart disease (CHD) can have genetic and other extracardiac malformations, which add to the short- and long-term risk of morbidity and perhaps mortality. We sought to examine our center's practice of screening for extracardiac anomalies and to determine the yield of these tests among specific cardiac diagnostic categories. Design. Retrospective review of infants admitted to the cardiac intensive care unit with a new diagnosis of CHD. Subjects were categorized into six groups: septal defects (SD), conotruncal defects (CTD), single-ventricle physiology (SV), left-sided obstructive lesions (LSO), right-sided obstructive lesions (RSO), and "other" (anomalous pulmonary venous return, Ebstein's anomaly). Screening modalities included genetic testing (karyotype and fluorescent in situ hybridization for 22q11.2 deletion), renal ultrasound (RUS), and head ultrasound (HUS). Results. One hundred forty-one patients were identified. The incidence of cardiac anomalies was: CTD (36%), SD (18%), SV (18%), LSO (14%), RSO (3%), and "other" (8%). Overall 14% had an abnormal karyotype, 5% had a deletion for 22q11.2, 28% had an abnormal RUS and 22% had abnormal HUS. Patients in SD and SV had the highest incidence of abnormal karyotype (36% and 17%); 22q11.2 deletion was present only in CTD and LSO groups (9% and 7%, respectively); abnormal RUS and HUS were seen relatively uniformly in all categories. Premature infants had significantly higher incidence of renal 43% vs. 24%, and intracranial abnormalities 46% vs. 16%. Conclusion. Infants with critical CHD and particularly premature infants have high incidence of genetic and other extracardiac anomalies. Universal screening for these abnormalities with ultrasonographic and genetic testing maybe warranted because early detection could impact short and long-term outcomes. PMID- 22070656 TI - Biocathodic nitrous oxide removal in bioelectrochemical systems. AB - Anthropogenic nitrous oxide (N(2)O) emissions represent up to 40% of the global N(2)O emission and are constantly increasing. Mitigation of these emissions is warranted since N(2)O is a strong greenhouse gas and important ozone-depleting compound. Until now, only physicochemical technologies have been applied to mitigate point sources of N(2)O, and no biological treatment technology has been developed so far. In this study, a bioelectrochemical system (BES) with an autotrophic denitrifying biocathode was considered for the removal of N(2)O. The high N(2)O removal rates obtained ranged between 0.76 and 1.83 kg N m(-3) net cathodic compartment (NCC) d(-1) and were proportional to the current production, resulting in cathodic coulombic efficiencies near 100%. Furthermore, our experiments suggested the active involvement of microorganisms as the catalyst for the reduction of N(2)O to N(2), and the optimal cathode potential ranged from -200 to 0 mV vs standard hydrogen electrode (SHE) in order to obtain high conversion rates. Successful operation of the system for more than 115 days with N(2)O as the sole cathodic electron acceptor strongly indicated that N(2)O respiration yielded enough energy to maintain the biological process. To our knowledge, this study provides for the first time proof of concept of biocathodic N(2)O removal at long-term without the need for high temperatures and expensive catalysts. PMID- 22070654 TI - Indole alkaloids and quassinoids from the stems of Brucea mollis. AB - Seven new indole alkaloids, bruceollines H-N (1-7), three new quassinoids, yadanziolides T-V (10-12), and four known analogues, bruceolline E (8), bruceolline F (9), bruceine D (13), and yadanziolide B (14), were isolated from an ethanol extract of the stems of Brucea mollis. The absolute configurations of compounds 2 and 5 were determined by comparison of their experimental and calculated ECD spectra. The absolute configuration of the known compound 9 was determined by using Mo2(OAc)4-induced CD analysis for the first time. Compounds 10, 13, and 14 exhibited cytotoxic activities with IC50 values of 3.00-5.81 MUM. PMID- 22070657 TI - The physical health of the seriously mentally ill: an overview of the literature. AB - Despite the wealth of literature which attests to the relationship between serious mental illness (SMI) and physical ill health, the provision of optimum physical health care for mental health service users remains a challenge. In England the Department of Health has identified the evident health inequalities for people with SMI as a priority area for health improvement, publishing numerous policy directives aimed at addressing these inequalities. However, this is a highly complex process and little is known about why the rhetoric of holistic health care has proved unattainable thus far. In this paper we present an informed commentary of the contemporary literature with the aim of offering a more comprehensive understanding of the health inequalities faced by people with SMI. We searched relevant databases for publications related to: the causes of poor physical health among the mentally ill, strategies to address these health needs and the impact which professional education, culture and services structure has on this facet of service delivery. This enabled us to identify potential strategies that can be adopted by health care practitioners wishing to improve the health of this vulnerable group, and by educationalists to advance professionals' knowledge of this important and ostensibly neglected area. PMID- 22070658 TI - The role of Government policy in supporting nurse-led care in general practice in the United Kingdom, New Zealand and Australia: an adapted realist review. AB - AIM: This article is a report on a review that examined the role of Government policy in primary care and its association with nurse-led care in the United Kingdom, New Zealand and Australia between 1998 and 2009. BACKGROUND: The United Kingdom, New Zealand and Australia share a similar model of first point access to the healthcare system via general practitioners. General practice is synonymous with the term primary care. DATA OURCES: Medline, CINAHL, EMBASE, Scopus, PsychInfo, Google, Department of Health, England (United Kingdom), Ministry of Health, New Zealand, Department of Health and Ageing, Australia. Searches of electronic databases from 1998 to December 2009 and hand searches of identified leads and key journals. Historical papers accessed to describe the genesis of practice nursing and historical Government policy documents prior to 1998, were examined. REVIEW METHODS: A modified realist review was used to synthesize research and policy documents relating to government policies pertaining to nurse-led care. In addition, a systematic review was used to identify literature that described practice nurse-led care. Results. Nurse-led primary care services are well described in the United Kingdom with a total of 45 studies meeting the inclusion criteria for the second review. There are no published studies from New Zealand, and only two from Australia describing nurse led primary care. CONCLUSION: New Zealand and Australia lag behind the United Kingdom in practice nurse development. Implementation of clinical governance was fundamental to the development of nurse-led care in the UK. PMID- 22070659 TI - UV/ozone-oxidized large-scale graphene platform with large chemical enhancement in surface-enhanced Raman scattering. AB - We fabricated a highly oxidized large-scale graphene platform using chemical vapor deposition (CVD) and UV/ozone-based oxidation methods. This platform offers a large-scale surface-enhanced Raman scattering (SERS) substrate with large chemical enhancement in SERS and reproducible SERS signals over a centimeter scale graphene surface. After UV-induced ozone generation, ozone molecules were reacted with graphene to produce oxygen-containing groups on graphene and induced the p-type doping of the graphene. These modifications introduced the structural disorder and defects on the graphene surface and resulted in a large chemical mechanism-based signal enhancement from Raman dye molecules [rhodamine B (RhB), rhodamine 6G (R6G), and crystal violet (CV) in this case] on graphene. Importantly, the enhancement factors were increased from ~10(3) before ozone treatment to ~10(4), which is the largest chemical enhancement factor ever on graphene, after 5 min ozone treatment due to both high oxidation and p-doping effects on graphene surface. Over a centimeter-scale area of this UV/ozone oxidized graphene substrate, strong SERS signals were repeatedly and reproducibly detected. In a UV/ozone-based micropattern, UV/ozone-treated areas were highly Raman-active while nontreated areas displayed very weak Raman signals. PMID- 22070660 TI - Blood donation on posters: a worldwide review. AB - Originally pasted on walls and on locations reserved specially for that purpose, the poster is a medium for advertising and promotion to be seen on the streets and in public places. More recently, it has spread, in a smaller format, on dedicated indoor sites: billboards, columns, street furniture, and so forth. For transfusion, it appeared early on that the poster constitutes an important medium to promote blood donation. Thousands of posters supporting regional, national, or international blood donation campaigns have been created all over the planet, with a great variability of images, symbols, and slogans, which are particularly revealing about the image and the reality of blood donation. The topic is rich in information, particularly sociologic, on the variety of ways in which transfusion organizations promote blood donation. The authors present in this article the results of a study based on a total of 283 posters from nations on every continent, divided into 24 different themes. PMID- 22070661 TI - Acupuncture for posttraumatic stress disorder: conceptual, clinical, and biological data support further research. AB - Posttraumatic stress disorder (PTSD) is common, debilitating, and has highly heterogeneous clinical and biological features. With the exception of one published preliminary clinical trial, rationale in support of the efficacy of acupuncture, a modality of Chinese medicine (CM), for PTSD has not been well described. This is a focused review of conceptual and clinical features of PTSD shared by modern western medicine (MWM) and CM, and of biological mechanisms of acupuncture that parallel known PTSD pathology. MWM and CM both recognize individual developmental variables and interactions between external conditions and internal responses in the genesis of PTSD. There is one published and one unpublished clinical trial that preliminarily support the efficacy of acupuncture for PTSD. Although there have been no mechanistic studies of acupuncture in human PTSD, extant research shows that acupuncture has biological effects that are relevant to PTSD pathology. Conceptual, clinical, and biological data support possible efficacy of acupuncture for PTSD. However, further definitive research about simultaneous clinical and biological effects is needed to support the use of acupuncture for PTSD in health care systems. PMID- 22070662 TI - The effect of pharmacotherapy on suicide rates in bipolar patients. AB - Suicide is a complex and multicausal human behavior and also a great challenge for psychiatry. We review the evidence available concerning pharmacological prevention of suicide in bipolar disorder patients. Several clinical trials provide evidence that effective acute and long-term treatment of bipolar depression provides a strong protection against suicide, suicide attempts, and probably against other complications of this disorder. Current major mood disorder is the most important risk factor of suicide, and bipolar II patients carry the highest risk. In bipolar patients suicidal behavior is most likely to occur during pure or mixed depressive episodes. Since bipolar disorder is a highly recurrent illness, adequate long-term pharmacotherapy is needed to prevent suicidal behavior. PMID- 22070663 TI - Degradation of seed mucilage by soil microflora promotes early seedling growth of a desert sand dune plant. AB - In contrast to the extensive understanding of seed mucilage biosynthesis, much less is known about how mucilage is biodegraded and what role it plays in the soil where seeds germinate. We studied seed mucilage biodegradation by a natural microbial community. High-performance anion-exchange chromatography (HPAEC) was used to determine monosaccharide composition in achene mucilage of Artemisia sphaerocephala. Mucilage degradation by the soil microbial community from natural habitats was examined by monosaccharide utilization tests using Biolog plates, chemical assays and phospholipid fatty acid (PLFA) analysis. Glucose (29.4%), mannose (20.3%) and arabinose (19.5%) were found to be the main components of achene mucilage. The mucilage was biodegraded to CO(2) and soluble sugars, and an increase in soil microbial biomass was observed during biodegradation. Fluorescence microscopy showed the presence of mucilage (or its derivatives) in seedling tissues after growth with fluorescein isothiocyanate (FITC)-labelled mucilage. The biodegradation also promoted early seedling growth in barren sand dunes, which was associated with a large soil microbial community that supplies substances promoting seedling establishment. We conclude that biodegradation of seed mucilage can play an ecologically important role in the life cycles of plants especially in harsh desert environments to which A. sphaerocephala is well adapted. PMID- 22070664 TI - Characterizing the rovibrational distribution of CD2CD2OH radicals produced via the photodissociation of 2-bromoethanol-d4. AB - This work characterizes the internal energy distribution of the CD(2)CD(2)OH radical formed via photodissociation of 2-bromoethanol-d(4). The CD(2)CD(2)OH radical is the first radical adduct in the addition of the hydroxyl radical to C(2)D(4) and the product branching of the OH + C(2)D(4) reaction is dependent on the total internal energy of this adduct and how that energy is partitioned between rotation and vibration. Using a combination of a velocity map imaging apparatus and a crossed laser-molecular beam scattering apparatus, we photodissociate the BrCD(2)CD(2)OH precursor at 193 nm and measure the velocity distributions of the Br atoms, resolving the Br((2)P(1/2)) and Br((2)P(3/2)) states with [2 + 1] resonance enhanced multiphoton ionization (REMPI) on the imaging apparatus. We also detect the velocity distribution of the subset of the nascent momentum-matched CD(2)CD(2)OH cofragments that are formed stable to subsequent dissociation. Invoking conservation of momentum and conservation of energy and a recently developed impulsive model, we determine the vibrational energy distribution of the nascent CD(2)CD(2)OH radicals from the measured velocity distributions. PMID- 22070665 TI - Clinicopathologic and gene expression parameters predict liver cancer prognosis. AB - BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model. METHODS: Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction. RESULTS: HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis. CONCLUSION: When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome. PMID- 22070666 TI - Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer. AB - BACKGROUND: The costs for loco-regional treatment of peritoneal carcinomatosis from gastric cancer are not well investigated. The aims of this study were to evaluate the costs and clinical outcome of systemic chemotherapy followed by cytoreductive surgery and intraperitoneal chemotherapy compared to systemic chemotherapy only in patients with peritoneal carcinomatosis from gastric cancer. MATERIAL AND METHODS: Ten patients were scheduled for systemic chemotherapy followed by loco-regional treatment. A reference group of 10 matched control patients treated with systemic chemotherapy only were used and both groups were evaluated with respect to clinical outcome and cost. RESULTS: The mean overall cost in the loco-regional group was $145,700 (range $49,900-$487,800) and $59,300 (range $23,000-$94,800) for the control group. The mean overall survival for the loco-regional group was 17.4 months (range 6.0-34.3), and 11.1 months (range 0.1 24.2) for the systemic chemotherapy only group. The gain in life-years was 0.52 and in quality-adjusted life-years 0.49, leading to incremental cost per life year and quality-adjusted life-years gained of $166,716 and $175,164, for loco regional group compared to systemic chemotherapy. DISCUSSION: Treatment of peritoneal carcinomatosis from gastric cancer is costly irrespective of treatment modality. If the survival benefit from adding loco-regional treatment to systemic chemotherapy indicated from this comparison is true, the incremental cost is considered high. PMID- 22070667 TI - Quality improvement in long-term mental health: results from four collaboratives. AB - This multiple case study evaluates four quality improvement collaboratives (QICs) in long-term mental health care focusing on social psychiatric care, recovery oriented care, social participation and somatic co-morbidity of psychiatric patients. The aim is to explore (1) effectiveness in terms of objective outcome indicators and impact of changes as perceived by team members; and (2) associations between collaborative-, organizational- and team-level factors and perceived effectiveness. Most objective outcomes, such as health, loneliness and clients' problem areas, showed significant improvement. Because of the diversity in content no single measure for objective effectiveness could be computed across the four collaboratives. Perceived effectiveness of team members was used as an indicator of the overall impact. In all, 55 of the 94 participating team leaders and 117 remaining team members completed a written survey at the end of each quality improvement collaborative. Multilevel regression analyses indicated that innovation attributes, appropriate measures, usable data collection tools and an innovative team culture could explain variation in perceived effectiveness. In conclusion, overall positive changes for clients were realized as demonstrated by objective outcomes and team members' perceptions of improvements in care processes. The results supported the notion that a layered approach is necessary to achieve improvements in quality of care. PMID- 22070668 TI - Relationships between tumour necrosis factor-alpha, interleukin-12B and interleukin-10 gene polymorphisms and hepatitis B in Chinese Han haemodialysis patients. AB - AIM: To investigate the possible association of gene polymorphisms of tumour necrosis factor (TNF)-alpha (-238 and -308), interleukin (IL)-10 (-592 and -819) and 3' untranslated region (3'UTR) of the IL12B (-1188) and hepatitis B in Chinese Han haemodialysis (HD) patients. METHODS: The genotyping of TNF-alpha 238 and -308, IL-10 -592 and -819 and 3'UTR of the IL12B were performed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. RESULTS: The TNF-alpha-238 A allele, the IL12B 3'UTR C/C, C/A genotypes were associated with decreased susceptibility to hepatitis B viral infection (P = 0.047, P = 0.003 and P = 0.001 respectively). The frequencies of IL-10-592 A/A genotype, IL-10-819 T/T genotype were lower in the HBV persistence group (P = 0.029 and P = 0.019) than those in the virus clearance group. CONCLUSIONS: TNF alpha and IL12B 3'UTR gene polymorphisms may be associated with HBV susceptibility and IL-10 gene polymorphisms may be related to the HBV persistence infection in Chinese Han HD patients. PMID- 22070669 TI - Thrombotic microangiopathy after living-donor liver transplantation. AB - Thrombotic microangiopathy (TMA) is an infrequent but severe life-threatening disorder in solid organ transplant recipients. Few studies of TMA in living donor liver transplant (LDLT) recipients, however, have been reported. We investigated the clinical characteristics and prognostic factors of TMA after LDLT. Among 393 adult LDLT recipients, 30 patients (7.6%) were identified to have TMA. The 1-, 3- and 5-year survival rates of these patients were lower (60.6%, 52.5% and 47.7%, respectively) than those of patients without TMA (93.0%, 89.0% and 87.3%, respectively). Multivariate analysis confirmed that reduced administration of fresh frozen plasma and sensitization against HLA are closely related with TMA (odds ratio [OR]: 2.6 and 16.1, respectively). However, a review of the cases revealed that individual responses to treatment varied considerably and the main etiologies were difficult to determine. A comparison of the clinical factors suggested that late onset (>30 days), poor response to treatment and delayed diagnosis and/or treatment are associated with a poor outcome. Because the prevention of TMA in LDLT patients is difficult, early diagnosis and initiation of intensive therapies may be crucial to improve the prognosis. PMID- 22070670 TI - Quantification of the kinetics and extent of self-sorting in three dimensional spheroids. AB - The self-sorting of cells into distinct compartments in three-dimensional (3D) microtissues is a process critical to developmental biology, cancer metastasis, and tissue engineering. Although self-sorting has been studied since the 1950s, little quantitative data exist that describe this dynamic process. Here, we describe a recently developed assay designed to quantify the extent and kinetics of self-sorting in 3D. Mixtures of fluorescently labeled normal human fibroblasts (NHF) and hepatocyte (H35) cells were fluorescently labeled, red and green respectively, and seeded onto micro-molded non-adhesive hydrogels. The cells self assembled into a spheroid and self-sorted with NHFs forming the central core and H35s forming the outer shell. A time course of fluorescent images was used to analyze the ratio of red (NHFs) and green (H35s) fluorescence in concentric hollow cylinders throughout a spheroid and was statistically compared with the fluorescent ratio of the perfectly sorted spheroid. We found that NHFs and H35s, at a 1:1 ratio, sorted to a final extent of 88+/-3% at an initial rate of 0.36+/ 0.06% per minute and reached 50% self-sorted at 2.7+/-0.3 h. Studies with varying ratios of NHFs and H35s show that self-sorting and self-assembly are coincident in time when the proportion of NHFs are varied over a 6-fold range (14% to 85%). This method can, thus, be used to characterize the sorting behavior of additional pairs of cells, the effect of drugs, and growth factors that may change the kinetics of the process, and bring an understanding to the cellular mechanisms which control self-sorting. PMID- 22070671 TI - Allylic substitution on cyclopentene and -hexene rings with alkynylcopper reagents. AB - Substitution of cyclic allylic picolinates with a reagent derived from TMS C=CMgBr and a copper salt was investigated. Although the previous type of reagent (TMSC=CMgBr and CuBr.Me(2)S) developed for linear allylic picolinates was less product selective and regioselective, the Cu(acac)(2)-derived reagent was highly selective (94-95%) to afford the S(N)2' product in good yields. As an application, several C-C bond formations at the acetylenic carbon and the synthesis of the PG intermediate were studied with success. PMID- 22070672 TI - The use of analogy in speech motor performance. AB - The acoustic correlates of pitch variation were examined in 40 participants who received analogy instructions or explicit instructions that required them to modulate their intonation during speech production. First, using focus group methodology, professional speech-language pathologists were asked to identify analogies that best described minimum pitch variation (monotone), moderate pitch variation (normal intonation), and maximum pitch variation (exaggerated intonation) in speech. The focus group established that an appropriate pitch variation metaphor may be related to imagery of "waves at sea", with minimum pitch variation represented by a flat calm sea, moderate pitch variation represented by a moderate sea, and maximum pitch variation represented by a choppy sea. Forty adult participants without speech impairments were asked to read aloud a standard paragraph using their habitual pitch variation (control condition). They were then allocated randomly to an analogy or an explicit instruction group and were asked to read aloud different paragraphs with minimum, moderate, or maximum pitch variations. Results revealed that acoustic correlates of pitch variation (standard deviation of fundamental frequency, SDF0) were not different for the control condition, or moderate and maximum pitch variation conditions in the two groups. However, the analogy instruction was significantly more effective than the explicit instruction for inducing minimum pitch variation. Analysis of participants in each group who showed higher than normal pitch variation in the control condition (>.5 SD above the group SDF0) revealed that the analogy instruction was more effective than the explicit instruction in the minimum variation condition. It was concluded that analogy instructions may be a useful tool in speech rehabilitation. PMID- 22070673 TI - Female caregivers' perceptions of reasons for violent behaviour among nursing home residents. AB - Threats and violence against professional caregivers present a growing health and safety problem in elderly care. We aimed to explore female caregivers' perceptions of reasons for violent behaviour among nursing home residents. Forty one caregivers at three nursing homes were interviewed and their responses were subjected to qualitative content analysis, which revealed three content areas of perceived reasons for patient violence: patient characteristics, caregiver approach and environmental aspects. The caregivers' perceptions were formulated in three core statements: 'they (the residents) are not who they used to be', 'we (the caregivers) have acted inappropriately' and 'we (residents and caregivers) are all surrounded by disorder'. Our findings indicate that the reasons for violence are complex and multifactorial, so interventions should be individually tailored. Caregivers involved in a violent situation need to see the person behind the behaviour, try to interpret what the behaviour is meant to communicate and adjust the intervention according to individual need. PMID- 22070674 TI - Headache and papilledema in an adult with cyanotic congenital heart disease: the importance of fundoscopic evaluation rather than phlebotomy. AB - Headaches and blurred vision in patients with cyanotic congenital heart disease and secondary erythrocytosis may be attributed to hyperviscosity and traditionally were treated with phlebotomy. In the current era, phlebotomy is rarely performed in these patients except in cases of hemoptysis or hyperviscosity symptoms. We report a case of a patient with a history of complex cyanotic congenital heart disease and secondary erythrocytosis who presented with headache and visual changes. He was found to have bilateral papilledema and increased intracranial pressure. Reduction of intracranial pressure with acetazolamide therapy led to alleviation of headache and visual changes. This demonstrates the need for formal ophthalmologic evaluation of these patients to assess other treatable causes of headache and visual changes before considering phlebotomy. PMID- 22070675 TI - Prevalence of human papillomavirus in mobile tongue cancer with particular reference to young patients. AB - The carcinogenetic role of human papillomavirus (HPV) in mobile tongue cancer remains unclear because of conflicting results reported in the literature. This disparity is likely to be due to variations in the samples and methods used. Furthermore, despite a tendency for increased prevalence of mobile tongue cancer in young adults, only a few reports specifically in young patients have been published. In the present study on 32 patients, including six in their 20s, we genotyped the prevalence of HPV using a highly sensitive detection tool in fresh frozen samples from surgical specimens and a novel detection device with electrochemical DNA chip and loop-mediated isothermal amplification. In addition, we confirmed HPV prevalence by in situ hybridization and immunohistochemistry for the p16(INK4a) protein, regarded as a biomarker of HPV-associated cancers. The frequency of 13 genotypes of high-risk HPV was 0/32 (0%), which was further confirmed by in situ hybridization. Overexpression of p16(INK4a) protein was observed in six of the 32 patients (19%), with four (67%) also overexpressing p53. Because there is usually a lack of p53 overexpression in HPV-associated cancer, it is unlikely that p16(INK4a) protein overexpression is correlated with HPV infection. Consequently, it is unlikely that HPV infection plays an important role in mobile tongue carcinogenesis, in particular in young adults. In addition, our data suggest that the overexpression of p16(INK4a) protein is not an appropriate biomarker for HPV association in mobile tongue carcinogenesis. PMID- 22070676 TI - How is dispersal integrated in life histories: a quantitative analysis using butterflies. AB - As dispersal plays a key role in gene flow among populations, its evolutionary dynamics under environmental changes is particularly important. The inter dependency of dispersal with other life history traits may constrain dispersal evolution, and lead to the indirect selection of other traits as a by-product of this inter-dependency. Identifying the dispersal's relationships to other life history traits will help to better understand the evolutionary dynamics of dispersal, and the consequences for species persistence and ecosystem functioning under global changes. Dispersal may be linked to other life-history traits as their respective evolutionary dynamics may be inter-dependent, or, because they are mechanistically related to each other. We identify traits that are predicted to co-vary with dispersal, and investigated the correlations that may constrain dispersal using published information on butterflies. Our quantitative analysis revealed that (1) dispersal directly correlated with demographic traits, mostly fecundity, whereas phylogenetic relationships among species had a negligible influence on this pattern, (2) gene flow and individual movements are correlated with ecological specialisation and body size, respectively and (3) routine movements only affected short-distance dispersal. Together, these results provide important insights into evolutionary dynamics under global environmental changes, and are directly applicable to biodiversity conservation. PMID- 22070677 TI - Tailored chemotherapy based on tumour gene expression analysis: breast cancer patients' misinterpretations and positive attitudes. AB - The aim of this study was to document how breast cancer patients perceive their prognosis and a tailored treatment based on tumour gene expression analysis, and to identify the features of this approach that may impact its clinical application. In-depth interviews were conducted at three French cancer centres with 37 women (35-69 years of age) with node-positive breast cancer undergoing an adjuvant chemotherapy regimen defined on the basis of the genomic signature predicting the outcome after chemotherapy. Several concerns were identified. First, some misconceptions about these methods were identified due to semantic confusions between the terms 'genomic' and 'genetic', which generated anxiety and uncertainty about the future. Second, the 'not done' and 'not interpretable' signatures were misinterpreted by the women and associated with highly negative connotations. However, the use of tumour genomic analysis to adapt the treatment to each patient received most of the patients' approval because it was perceived as an approach facilitating personalised medicine. In conclusion, improving the quality of provider/patient communications should enable patients to play a more active part in the decision making about their treatment. This will ensure that those who agree to have tumour gene analysis have realistic expectations and sound deductions about the final result disclosure process. PMID- 22070678 TI - Quercetin as a systemic chemopreventative agent: structural and functional mechanisms. AB - There is a growing focus on diet and the use of naturally abundant compounds as supplements because their properties have many potential health benefits with minimal side effects. The flavonol-type flavonoid quercetin has increased in popularity because it is a highly studied, multidimensional bioactive compound that possesses both antioxidant properties and the ability to modulate signal transduction pathways. Direct antioxidant properties may play a role in the abrogation of both DNA damage, but potentially of more importance quercetin, can also target multiple signaling pathways associated with oncogenesis and tumor progression, which include DNA damage, inflammation and obesity. Quercetin can also upregulate proteins that abrogate free radical damage, such as p53. The concurrent targeting of quercetin's multiple bioactivities presents a potent chemopreventative strategy, but because bioavailability of quercetin is poor it will be necessary to develop quercetin analogs to maximize the full chemopreventative potential of the compound. This review will explore the structural and mechanistic properties of quercetin as they relate to its ability to act as a chemopreventative compound. A better understanding of quercetin's mechanistic properties could aid in the rational design of more potent or bioavailable flavonol-type compounds. PMID- 22070680 TI - Natural polyphenols and cardioprotection. AB - With more than 8000 polyphenols found in food (mainly, wine, tea, coffee, cocoa, vegetables and cereals), many epidemiological studies suggest that the intake of polyphenol-rich foods has a beneficial effect on a large number of cardiovascular risk factors, such as high blood pressure, high blood cholesterol, obesity, diabetes and smoking. The mechanisms involved in the cardioprotective effects of polyphenols are numerous and include antioxidant, vasodilator, anti-inflammatory, anti-fibrotic, antiapoptotic and metabolic. Most importantly, recent experimental data demonstrate that polyphenols can exert its cardioprotective effect via the activation of several powerful prosurvival cellular pathways that involve metabolic intermediates, microRNAs, sirtuins and mediators of the recently described reperfusion injury salvage kinases (RISK) and survivor activating factor enhancement (SAFE) pathways. PMID- 22070681 TI - Polyphenols and neuroprotection against ischemia and neurodegeneration. AB - Neuroprotection of polyphenols in medical plants is getting attention in the world. Scutellaria baicalensis, paeonia veitchii and paeonia suffruticosa have been extensively studied in the last 10 years and show multi-function. They are neuroprotectants, antioxidants, anti-inflammatory and antithrombic agents as well as vasoconstriction inhibitors and amyloid-peptide (Abeta) cleaners by means of their polyphenols: baicalin, baicalein, wogonin (in scutellaria), and paeonol, paeonoside, paeoniflorin (PF) and 1, 2, 3, 4, 6-Penta-O-galloyl-beta-D-glucose (PGG) (in paeonia veitchii and paeonia suffruticosa). Other 4 medical plants: astragali, ligusticum wallichii, angelica sinensis and carthamus tinctorius (saffron) have been the major medicines to treat ischemia for hundreds of years in China, Korea and Japan. Our recent experimental studies demonstrated the neuroprotective efficacy of the combination of these phyotmedicines on mitigating brain infarction and global ischemia as well as preventing the neurodegeneration following ischemia. Owing to their multi-function, including improving cerebral blood circulation, they therefore have the potential to alleviate the symptoms of degenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). Pharmacology of the 7 herbs and their major relative polyphenols is depicted in the article. PMID- 22070682 TI - An overview of innovations in analysis and beneficial health effects of wine polyphenols. AB - Polyphenols are natural compounds that show a wide spectrum of biological actions potentially beneficial for the human health. Wine is an alcoholic beverage that contains a large amount of polyphenols extracted from grapes during the processes of vinification. These molecules are associated with anticancerogenic, antidiabetic, neuroprotective, hormonal, antimicrobial, cardioprotective, and other health effects of wine. The present review provided an overview of well know and recent achievement in analytical methodology for the analysis of polyphenols in wine, and their biological activities. PMID- 22070679 TI - Polyphenols: skin photoprotection and inhibition of photocarcinogenesis. AB - Polyphenols are a large family of naturally occurring plant products and are widely distributed in plant foods, such as, fruits, vegetables, nuts, flowers, bark and seeds, etc. These polyphenols contribute to the beneficial health effects of dietary products. Clinical and epidemiological studies suggest that exposure of the skin to environmental factors/pollutants, such as solar ultraviolet (UV) radiation induce harmful effects and leads to various skin diseases including the risk of melanoma and non-melanoma skin cancers. The incidence of non-melanoma skin cancer, comprising of squamous cell carcinoma and basal cell carcinoma, is a significant public health concern world-wide. Exposure of the skin to solar UV radiation results in inflammation, oxidative stress, DNA damage, dysregulation of cellular signaling pathways and immunosuppression thereby resulting in skin cancer. The regular intake of natural plant products, especially polyphenols, which are widely present in fruits, vegetables, dry legumes and beverages have gained considerable attention as protective agents against the adverse effects of UV radiation. In this article, we first discussed the impact of polyphenols on human health based on their structure-activity relationship and bioavailability. We then discussed in detail the photoprotective effects of some selected polyphenols on UV-induced skin inflammation, proliferation, immunosuppression, DNA damage and dysregulation of important cellular signaling pathways and their implications in skin cancer management. The selected polyphenols include: green tea polyphenols, pomegranate fruit extract, grape seed proanthocyanidins, resveratrol, silymarin, genistein and delphinidin. The new information on the mechanisms of action of these polyphenols supports their potential use in skin photoprotection and prevention of photocarcinogenesis in humans. PMID- 22070683 TI - Analysis of flavonoids in foods and biological samples. AB - Flavonoids are a major class of plant phenolics that are widely distributed in the human diet and have been related to health promotion. They may occur in their natural sources in free forms (aglycones), as glycosylated or acylated derivatives, or as oligomeric and polymerized structures. This structural diversity affects their physicochemical behaviour and complicates their analysis. Thus, there is not a single standardized procedure that can be recommended for all flavonoid groups and/or type of samples, and the procedures have to be optimized depending on the nature of the sample and the target analytes. Furthermore, when dealing with the analysis of flavonoids biological samples (i.e., human and animal fluids and tissues) some differential aspects have to be taken into account; the nature of the compounds that can be found in those samples may differ from that present in plants and food, and flavonoids and metabolites occur in much lower concentrations, which make their analysis still more challenging. In this review the main techniques for extraction and analysis of flavonoids in foodstuffs and biological fluids are revised, as well as their occurrence in foods and beverages and available databases. PMID- 22070684 TI - Polyphenols and cardiovascular disease: a critical summary of the evidence. AB - Epidemiological studies are clear: diets in which plant foods provide the major portion of caloric intake, e.g. the Mediterranean and the Japanese diets, are associated with a reduced risk of certain degenerative diseases like cancer and atherosclerosis. Although fats and proteins in plants, as opposed to those of animal origin, are responsible to some extent for these protective effects, the contribution of other plant food components may also be relevant. In the past few years, research on polyphenols has remarkably expanded and is unveiling several biological activities of these compounds. Alas, the marketing departments of several industries are jumping ahead of solid scientific evidence; as a consequence, unsubstantiated claims are being made and whole foods or fortified, enriched, or enhanced foods are being created and sold. Science is beginning to corroborate some of these claims, but much more research is needed and several myths are to be disproven. In this mini-review we critically discuss the current limitations of polyphenol research and we contend that, in addition to their putative antioxidant action, several biochemical and physiological processes might be influenced by polyphenols. PMID- 22070685 TI - Editorial: introduction to polyphenols, plant chemicals for human health. PMID- 22070686 TI - GPE and GPE analogues as promising neuroprotective agents. AB - The tripeptide glycine-proline-glutamate (GPE) is the naturally cleaved N terminal tripeptide of insulin-like growth factor-1 (IGF-1) in brain tissues by an acid protease. Although GPE does not bind to IGF-1 receptors and its mode of action is not clear, in vitro studies have demonstrated its ability to stimulate acetylcholine and dopamine release, as well as to protect neurones from diverse induced brain injures. More importantly, GPE has been shown to have potent neuroprotective effects in numerous animal models of hypoxic-ischemic brain injury and neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's diseases. As a consequence, GPE was suggested to be a potential target for the rational design of neuroprotective agents. Unfortunately, the use of GPE as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. This review will focus on structural modifications performed on the GPE molecule in order to obtain bioactive analogues with increased pharmacokinetic profile useful for the treatment of central nervous system (CNS) injures and neurodegenerative disorders. PMID- 22070688 TI - CDC25 phosphatase inhibitors: an update. AB - The cell division cycle 25 (CDC25) family of proteins is a group of highly conserved dual-specificity phosphatases. They are key regulators of normal cell division and the cell response to DNA damage, and play a fundamental role in transitions between cell cycle phases during normal cell division, via the activation of CdK/cyclin complexes. Their abnormal expression, detected in a number of tumors, often correlated with a poor clinical prognosis, implies that their dysregulation is involved in malignant transformation. Thus, inhibition of these proteins represents an attractive therapeutic target in oncology, as evidenced from many patents and papers published on the subject in recent years. Hence, this review aims to provide an overview of recent developments in the field of CDC25 phosphatase inhibitor design since 2008. PMID- 22070689 TI - Cell adhesion molecules as pharmaceutical target in atherosclerosis. AB - Cell adhesion molecules (CAMs) are transmembrane proteins that mediate adhesion and interactions between cells or cell and extra-cellular matrix. Increased expression and activation of CAMs in vascular endothelial cells and circulating leukocytes, as occurring in the settings of inflammation, hypercholesterolemia, hypertension and diabetes, stimulates leukocyte recruitment into the vascular endothelium, an important step in the pathogenesis of atherosclerosis. CAMs are a potential therapeutic target in clinical practice and in recent years pharmaceutical agents with specific effects on the production and function of these molecules have been studied and developed. This article reviews recent progress regarding pathophysiology of CAMs in atherogenesis and pharmaceutical products or chemicals that are active against CAMs, and assesses the possibilities for clinical developments in this area that might enhance the prevention, monitoring and treatment of atherosclerotic cardiovascular diseases. PMID- 22070690 TI - 2,5-diketopiperazines as neuroprotective agents. AB - 2,5-diketopiperazines are the simplest cyclic peptides found in nature, commonly biosynthesized from amino acids by different organisms, and represent a promising class of biologically active natural products. Their peculiar heterocyclic structure confers high stability against the proteolysis and constitutes a structural requirement for the active intestinal absorption. Furthermore, the diketopiperazine-based motif is considered as a novel brain shuttle for the delivery of drugs with limited ability to cross the blood-brain barrier (BBB) and can be proposed as an ideal candidate for the rational development of new therapeutic agents. Although these cyclic peptides have been known since the beginning of the 20th century, only recently have they attracted substantial interest with respect to the wide spectrum of their biological properties, including antitumor, antiviral, antifungal, antibacterial and antihyperglycemic activities. In addition to these, the most challenging function of the diketopiperazine derivatives is related with their remarkable neuroprotective and nootropic activity. The aim of the present paper is to provide an overview of the two major classes of diketopiperazines, the TRH-related and the unsaturated derivatives both characterized by a significant ability to protect against neurotoxicity in several experimental models. The neuroprotective profile of these compounds suggests that they may have a future utility in the therapy of neuronal degeneration in vivo, potentially through several different mechanisms. PMID- 22070691 TI - Ascorbic acid: an old player with a broad impact on body physiology including oxidative stress suppression and immunomodulation: a review. AB - Ascorbic acid is a low molecular weight antioxidant well known as anti-scorbut acting vitamin C in humans, primates and guinea pigs. This review summarizes basic data about ascorbic acid in its physiological action point of view. It is divided into biochemistry of ascorbic acid synthesis, mechanism of antioxidant action and participation in anabolism, pharmacokinetics and excretion, exogenous ascorbic acid immunomodulatory effect and participation in infectious diseases, impact on irradiation and intoxication pathogenesis, and supplementary demands. The primary intention was to consider ascorbic acid not only as an antioxidant but also as a chemical compound affecting multiple pathways with a potential beneficial impact in many diseases and processes in human body. PMID- 22070692 TI - Tetracyclines: drugs with huge therapeutic potential. AB - Tetracyclines are an amazing class of chemical agents with multiple therapeutic potential. Structural modification of the original natural tetracyclines led to the synthesis and development of doxycycline and minocycline, compounds with higher lipophilicity, better oral pharmacokinetics and higher potency. Due to diverse pharmacological properties, these drugs are now under extensive investigation for use in the treatment of various disparate diseases. In recent years, several studies have conclusively reported anti-inflammatory, immune modulating and neuroprotective effects of these compounds. There are currently over 200 ongoing clinical trials on tetracyclines. These studies extend over a wide range of diseases including dermatological diseases, behavior and mental disorders, immune system disorders, cardiovascular diseases, and cancer. In this review we will discuss the chemistry and pharmacology of these agents, and describe how their inhibitory effect on matrix metalloproteinase and on pro inflammatory cytokines has kindled renewed interest in them. Based on the reports from pre-clinical and clinical trials, the therapeutic potential and application of tetracyclines may well be redefined and extensively extended. PMID- 22070687 TI - Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease. AB - Phytoestrogens are estrogenic compounds of plant origin classified into different groups including isoflavones, lignans, coumestans and stilbenes. Isoflavones such as genistein and daidzein are the most studied and most potent phytoestrogens, and are found mainly in soy based foods. The effects of phytoestrogens are partly mediated via estrogen receptors (ERs): ERalpha, ERbeta and possibly GPER. The interaction of phytoestrogens with ERs is thought to induce both genomic and non genomic effects in many tissues including the vasculature. Some phytoestrogens such as genistein have additional non-ER-mediated effects involving signaling pathways such as tyrosine kinase. Experimental studies have shown beneficial effects of phytoestrogens on endothelial cells, vascular smooth muscle, and extracellular matrix. Phytoestrogens may also affect other pathophysiologic vascular processes such as lipid profile, angiogenesis, inflammation, tissue damage by reactive oxygen species, and these effects could delay the progression of atherosclerosis. As recent clinical trials showed no vascular benefits or even increased risk of cardiovascular disease (CVD) and CV events with conventional menopausal hormone therapy (MHT), phytoestrogens are being considered as alternatives to pharmacologic MHT. Epidemiological studies in the Far East population suggest that dietary intake of phytoestrogens may contribute to the decreased incidence of postmenopausal CVD and thromboembolic events. Also, the WHO-CARDIAC study supported that consumption of high soybean diet is associated with lower mortalities from coronary artery disease. However, as with estrogen, there has been some discrepancy between the experimental studies demonstrating the vascular benefits of phytoestrogens and the data from clinical trials. This is likely because the phytoestrogens clinical trials have been limited in many aspects including the number of participants enrolled, the clinical end points investigated, and the lack of long-term follow-up. Further investigation of the cellular mechanisms underlying the vascular effects of phytoestrogens and careful evaluation of the epidemiological evidence and clinical trials of their potential vascular benefits would put forward the use of phytoestrogens as an alternative MHT for the relief of menopausal symptoms and amelioration of postmenopausal CVD. PMID- 22070693 TI - Lysophospholipids: potential markers of diseases and infertility? AB - The in vivo concentration of lysophospholipids (LPL) such as lysophosphatidylcholine (LPC) increases under different pathological conditions and, thus, LPL attract nowadays considerable diagnostic and pharmacological interest. LPL are particularly interesting because they possess pro- and anti inflammatory properties and can be generated by two completely different pathways: either by the influence of (a) phospholipases and (b) different reactive oxygen species (ROS) that are generated in significant amounts under inflammatory conditions. This review provides a summary of the mechanisms by which LPL can be generated under in vitro and in vivo conditions. The focus will be on lysophosphatidylcholine (LPC) because this LPL is most abundant among all LPL and was, thus, most intensively studied so far. Additionally, biochemical, chromatographic and spectroscopic methods of LPL and LPC determinations will be discussed. Finally, the effects of LPL as signaling molecules and their roles in different pathologies such as infertility, cancer, atherosclerosis or inflammatory diseases are discussed. Special emphasis will be on the role of LPL in reproduction failures related to poor semen quality and, in that context, the potential role of LPC as a disease-indicative molecule. PMID- 22070694 TI - Pleuromutilin and its derivatives-the lead compounds for novel antibiotics. AB - Due to the rapid onset of resistance to most antibacterial drugs, research efforts are focusing on new classes of antibacterials with different mechanisms of action from clinically used antibacterials. Pleuromutilin derivatives have received more and more scientific attention for their unique mechanism of action. Two pleuromutilin derivatives, tiamulin and valnemulin have been successfully developed as antibiotics for veterinary use. Retapamulin, another pleuromutilin derivative has been approved for use in humans in April 2007 by Food and Drug Administration (FDA). It has been shown that there is rarely cross-resistance between pleuromutilin derivatives and other antimicrobial agents, and the development of resistance bacterial is still low. This review will demonstrate mechanism of action of pleuromutilin derivatives and reveal the structure activity relationship (SAR) of pleuromutilin derivatives. Additionally, the pleuromutilin antibacterial derivative agents in the market, such as tiamulin, valnemulin and retapamulin, will be discussed. It is proposed that new antibacterial agents might be developed from pleuromutilin derivatives in the future. PMID- 22070695 TI - Reticulate eruptions: Part 2. Historical perspectives, morphology, terminology and classification. AB - Reticulate eruptions of vascular origin may represent an underlying arterial, venous, microvascular or combined pathology. In the presence of arterial pathology, individual rings are centred around ascending arterial vessels that supply the corresponding area of skin within an arterial hexagon that clinically presents with a blanched centre. Confluence of multiple arterial hexagons generates a stellate (star-like) pattern. In the presence of a primary venous pathology, individual rings correspond to the underlying reticular veins forming multiple venous rings. Focal involvement of a limited number of vessels presents with a branched (racemosa) configuration while a generalized involvement forms a reticulate (net-like) pattern. 'Livedo' refers to the colour and not the pattern of the eruption. Primary livedo reticularis (Syn. cutis marmorata) is a physiological response to cold and presents with a diffuse blanchable reticulate eruption due to vasospasm of the feeding arteries and sluggish flow and hyperviscosity in the draining veins. Livedo reticularis may be secondary to underlying conditions associated with hyperviscosity of blood. Livedo racemosa is an irregular, branched eruption that is only partially-blanchable or non blanchable and always signifies a pathological process. Retiform purpura may be primarily inflammatory with secondary haemorrhage or thrombohaemorrhagic, as seen in disseminated intravascular coagulopathy. PMID- 22070696 TI - Mohs surgery histopathology concordance in Australia. AB - BACKGROUND: Mohs micrographic surgery is an important technique for dealing with difficult non-melanoma skin cancers. The ability of the Mohs surgeon to correctly interpret the histopathology is crucial to the practice of this surgery. This study sought to assess the concordance between a Mohs surgeon and a dermatopathologist in the reading of Mohs section histopathology slides. METHODS: This study was a retrospective study of Mohs frozen section histopathology slides of patients from a private Mohs practice. The slides were provided for assessment by a dermatopathologist who had to interpret the histopathology and mark on a Mohs map the location of the tumour. RESULTS: We demonstrate a 95% agreement between the Mohs surgeon and the dermatopathologist in the interpretation of Mohs frozen section histopathology slides. CONCLUSION: An Australian Mohs surgeon is capable of correctly identifying and interpreting histopathology in non-melanoma skin cancers, and this compares favourably to an overseas study. PMID- 22070697 TI - Dermoscopic naevus patterns in people at high versus moderate/low melanoma risk in Queensland. AB - INTRODUCTION: Dermoscopic understanding of naevus characteristics is essential baseline knowledge for identifying early malignant changes. METHOD: This cross sectional study includes 34 patients (56% female, mean age 48 years) at high risk of melanoma (personal or a first degree family member with history of melanoma) and 31 moderate/low melanoma risk volunteers (55% female, mean age 37 years) recruited at the Princess Alexandra Hospital, Brisbane, between October 2009 and March 2010. Participants received full body and individual dermoscopic imaging of clinically significant naevi (>=2 mm on the back of male/female and lower limbs of female and >=5 mm at other body sites). Dermoscopic patterns of naevi were compared between people at high versus moderate/low melanoma risk according to age and body site. RESULTS: In both high and moderate/low risk groups, globular naevi predominated on the head/neck and abdomen/chest, reticular and non-specific naevi on the back, and non-specific pattern on the upper and lower limbs. Non specific naevi were the most common in all age groups. In both risk groups, globular naevi were more frequent in the younger age bracket, and reticular naevi were more frequent in the older age bracket. Mixed naevus patterns were infrequent and were more common in the younger age brackets of both risk groups. CONCLUSION: Our preliminary data shows that dermoscopic naevus patterns were similar for age and body site in people at different levels of melanoma risk, suggesting high melanoma risk does not influence dermoscopic naevus patterns. PMID- 22070698 TI - New insights in naevogenesis: number, distribution and dermoscopic patterns of naevi in the elderly. AB - BACKGROUND/OBJECTIVES: It is well recognized that the number and patterns of acquired melanocytic naevi vary with age, but little is known about naevus patterns in the elderly. This is a cross-sectional study assessing the prevalence, dermoscopic pattern and anatomical distribution of naevus subtypes in a stratified cohort aged between 60 and 89 years. METHODS: Fifty-nine patients who attended the Queensland Institute of Dermatology were recruited randomly and evenly distributed into three age groups: 60-69 years; 70-79 years; and 80-89 years. For each participant, total naevus count and morphological naevus types were recorded with respect to age, sex and anatomical location. Flat (Clark's) naevi were further subclassified according to the dermoscopic pattern as reticular, globular or structureless. RESULTS: Using non-parametric methods, naevus counts in the elderly decreased due to the disappearance of reticular naevi (P < 0.05). By contrast, structureless and intradermal (Unna's and Miescher's) naevi seemed to persist even into older age. Naevi on the trunk, limbs, head and neck represented 57.6%, 31.0% and 11.3%, respectively. Notably, no reticular naevi were found on the head and neck area. CONCLUSIONS: There is a progressive reduction in total naevus counts with advancing age with respect to a cohort aged greater than 60 years. PMID- 22070699 TI - Tele-assessment of Psoriasis Area and Severity Index: a study of the accuracy of digital image capture. AB - BACKGROUND: The implementation of remote Psoriasis Area and Severity Index (PASI) determinations would greatly enhance the delivery of specialist dermatological care to patients with severe psoriasis unable to attend face-to-face dermatological consultations. Here we investigate the feasibility of the remote determination of PASI scores by comparing the results of face-to-face with digital image assessment. METHODS: Twelve patients with confirmed psoriasis were recruited for the study. Initially, two dermatologists scored the PASI at the patients' usual scheduled face-to-face visits, at which time standardized digital images were obtained. PASI scoring based on digital images was then performed on two separate occasions by three dermatologists with a time-interval period between assessments, facilitating an assessment of score reproducibility. Linear weighted kappa statistics were applied to the PASI scores to ascertain agreement between sets of observations. RESULTS: While we found a moderate (kappa = 0.51) agreement between the face-to-face scores, there was very good (kappa = 0.83) agreement between the first round of telescores and moderate (kappa = 0.60) agreement between the second round of telescores. Comparison between the face-to face and telescores revealed good (kappa = 0.67 and 0.63) agreement for the scorers respectively. CONCLUSION: We demonstrate that PASI scores can be determined with moderate to good accuracy by dermatologists using standardized digital images. Our results imply the implementation of a tele-PASI service may be a practical and effective adjunct to the dermatological care of patients with severe psoriasis where incapacity or distance prevent the realisation of face-to face consultations. PMID- 22070700 TI - Impact on the dermatology educational experience of medical students with the introduction of online teaching support modules to help address the reduction in clinical teaching. AB - BACKGROUND/OBJECTIVES: With increasing medical student numbers and decreasing clinical teaching opportunities, there has been a need to develop alternative learning resources. The aim of this study was to examine the effectiveness of a new dermatology online teaching resource, from a student perspective. METHODS: The Australasian College of Dermatologists developed an undergraduate dermatology curriculum and subsequently created online teaching modules in partnership with the University of Sydney. These modules were introduced to final year medical students at the University of Western Australia in 2010. The dermatology learning experiences of these 142 students were compared with the 2009 medical student cohort who did not have access to this resource. A self-administered questionnaire, with a 5-point rating scale, was used. RESULTS: The 2010 cohort described an improved educational experience using the online modules. Despite a reduction in the number of clinics attended, knowledge and skills gained were scored higher among the 2010 cohort. The student's confidence in their ability to manage common dermatological conditions was also statistically higher in the cohort with the online teaching resource. The learning experience for dermatology compared to other subspecialty teaching in medical school was ranked as a significantly more positive experience in the 2010 cohort. CONCLUSIONS: Our results suggest that the introduction of the online modules described in this paper to support learning have improved the perceived educational experience of medical students and should be incorporated as a way to improve student teaching in the face of reduced clinic teaching. PMID- 22070701 TI - Skin disease in the first two years of life in Aboriginal children in East Arnhem Land. AB - BACKGROUND: The most common skin infections affecting children in remote Aboriginal communities are scabies and impetigo. Group A streptococcal skin infections are linked to the high rates of heart and renal disease occurring in Aboriginal Australians. METHODS: A retrospective review of medical records was conducted in a primary health care centre in the East Arnhem region of the Northern Territory. Data was collected from all presentations to the clinic in the first 2 years of life for 99 children born between 2001 and 2005 as a component of the East Arnhem Regional Healthy Skin Project. RESULTS: The median number of presentations to the clinic in the first 2 years of life was 32. Skin disease was recorded in 22% of all presentations. By 1 year of age 82% of children had presented to the clinic with their first episode of impetigo and 68% with their first episode of scabies. Antibiotics were administered to 49% of children with impetigo. CONCLUSION: Skin infections are a major reason for presentation to primary health clinics and contribute to the high disease burden experienced by children in the first 2 years of life. This high frequency of presentation provides multiple opportunities for intervention and monitoring. PMID- 22070702 TI - The use of visual language as a search pattern in dermoscopy. PMID- 22070703 TI - Lymphomatoid papulosis in children: experience of five cases and the treatment efficacy of methotrexate. AB - We present a case series of childhood lymphomatoid papulosis (LyP), an entity which is commonly misdiagnosed and poorly described in the paediatric dermatology literature. Clinically and histologically, the features of LyP in children can mimic insect bite reactions, with prominent dermal neutrophils and eosinophils. However, CD30 immunohistochemical staining of atypical lymphocytes within a mixed inflammatory infiltrate should point to the diagnosis of LyP. There is no consensus to guide management of childhood LyP due to its rarity and largely unknown natural course. We discuss our experience with LyP in five children and the use of methotrexate to induce rapid resolution of persistent lesions and to reduce recurrences in two children. Although none of our cases have experienced malignant transformation to date, life-long monitoring is advocated. PMID- 22070704 TI - Juvenile xanthogranuloma: challenges in complicated cases. AB - Juvenile xanthogranuloma (JXG) is one of the most common forms of non-Langerhans cell histiocytosis in children. Although it usually presents as a self-limited skin lesion with typical histopathology, JXG can be challenging to diagnose due to an atypical initial presentation with corresponding variable histopathology for different stages of development. We present challenging cases of JXG from Sydney Children's Hospital, collected over 10 years - two with multisystem involvement and concomitant urticaria, one associated with neurofibromatosis, and one case of giant JXG with an initial histopathological challenge. Although JXG has been reported with urticaria pigmentosa, in two of our cases persistent urticaria, in association with JXG is discussed. PMID- 22070705 TI - Cryptococcosis presenting as upper limb cellulitis and ulceration: a case series. AB - We report four cases of cryptococcosis presenting as upper limb cellulitis or ulceration, or both. Three of the four patients were on long-term prednisolone therapy at the time of presentation. In each case, the diagnosis of cryptococcosis was established by a biopsy of the skin. Only one of the four patients had conclusive evidence of disseminated disease. Our cases highlight the importance of skin biopsy in immunosuppressed individuals presenting with cellulitis, particularly when the cellulitis occurs in an atypical location and when the clinical condition fails to respond to standard antibacterial therapy. PMID- 22070706 TI - A case of multicentric reticulohistiocytosis responsive to azathioprine in a patient with no underlying malignancy. AB - Multicentric reticulohistiocytosis (MRH), a rare histiocytic systemic condition characterized by mutilating arthritis and multiple cutaneous nodules, has been associated with malignancy including that of the breast, thyroid and colon. An unsubstantiated link with infectious agents such as mycobacterium tuberculosis has been described. Many treatments have been used with varying success. We describe the case of a 60-year-old man with MRH and no underlying malignancy who initially responded well to azathioprine and whose disease recurred upon cessation. A second course of azathioprine administered in conjunction with antituberculous treatment resulted in disease control. Broader associations and features of this rare disease are discussed. PMID- 22070707 TI - Merkel cell carcinoma metastatic to the transverse colon: disease free after six years - cure or just prolonged remission? AB - Merkel cell carcinoma is an uncommon but highly immunogenic skin malignancy that has the potential to metastasize to any site in the body. Despite treatment many patients experience relapse, often to distant sites beyond the site of initial treatment. The development of distant soft tissue or visceral metastases is considered incurable, despite treatment with prognosis usually being measured in months. We report the case of an elderly man who developed colonic metastases from a head and neck primary and with treatment has survived disease free for over 6 years. Such reports are infrequently documented and highlight the unpredictable nature of this disease. PMID- 22070708 TI - Palmoplantar keratoderma: an adverse reaction to influenza vaccination. AB - Acquired palmoplantar keratoderma (PPK) is a rare group of conditions with a number of aetiologies, including adverse reactions to drugs. Herein, we report a case of acquired PPK in association with influenza vaccination, confirmed by rechallenge. PMID- 22070709 TI - Porokeratosis of Mibelli: Involution and resolution with 5% imiquimod cream. AB - An 82-year-old woman presented with a longstanding, slowly enlarging annular lesion on the medial aspect of the ankle. Histology confirmed the clinical diagnosis of Porokeratosis of Mibelli. The lesion slowly involuted and resolved over 26 weeks of 5% imiquimod cream applied topically and has not recurred during a 36 month follow-up period. PMID- 22070715 TI - Autosomal dominant bullous dermolysis of the newborn associated with a heterozygous missense mutation p.G1673R in type VII collagen. AB - Bullous dermolysis of the newborn is an inherited mechano-bullous disorder classed as a rare subtype of dystrophic epidermolysis bullosa. Fewer than 30 cases of bullous dermolysis of the newborn have been reported in the literature and the pathogenesis of the disease is poorly understood. Only a minority of cases have had pathogenic mutations identified. We present a case of a neonate born to non-consanguineous Caucasian parents with an exon 54 (c.5017G > A, p.G1673R) mutation reported as one mutant allele in a case of recessive dystrophic epidermolysis bullosa (generalized other). PMID- 22070716 TI - Erythema annulare centrifugum-like mycosis fungoides. AB - A considerable number of recent reports have documented mycosis fungoides resembling many other dermatoses. Due to highly variable presentations and the sometimes non-specific nature of histological findings, an accurate diagnosis of mycosis fungoides can be difficult. Erythema annulare centrifugum-like mycosis fungoides with a variety of annular, polycyclic erythematous skin lesions is a recently recognized atypical manifestation of mycosis fungoides, and only a few cases have been reported to date. PMID- 22070717 TI - Metallic mercury vapour poisoning revisited. AB - Mercury poisoning was once common in the 19th century. With its declining use, now clinicians and the public in general are often unaware and unsuspecting of mercury toxicity. A 40-year-old woman and her two children were hospitalized with a 1-week history of a generalized lichenoid eruption. Clinical improvement occurred without a diagnosis; however, on returning home, features of acrodynia with digital gangrene developed in the woman, leading to suspicion of heavy metal poisoning. There was no recurrence after moving from their contaminated house. PMID- 22070718 TI - Pyogenic granuloma, port-wine stain and pregnancy. AB - We present a novel case of pyogenic granuloma occurring within a port-wine stain in two sequential pregnancies at different sites. There was no history of precipitating events such as trauma. We discuss why a pyogenic granuloma may occur within a port-wine stain and how pregnancy may increase the likelihood of this occurring. PMID- 22070720 TI - A novel, nonbinary evaluation of success and failure reveals bupropion efficacy versus methamphetamine dependence: reanalysis of a multisite trial. AB - A multisite, double-blind, placebo-controlled trial of bupropion for methamphetamine dependence was reanalyzed using a novel, nonbinary method of evaluating success and failure. The original analysis focused on a group response endpoint (the change in percentage of participants with methamphetamine-free urines each week over the course of the trial) and no significant bupropion effect was observed in the total population of study participants. In this reanalysis, individual participants were regarded as treatment success if they achieved multiple weeks of abstinence lasting through the end of the study, and their degree of success was quantified by calculating the number of beyond threshold weeks of success (NOBWOS). Thus, setting the threshold at 1 week of end of-study abstinence (EOSA), treatment successes were assigned NOBWOS values ranging from 1 to 11, with 1 corresponding to 2 weeks EOSA and 11 corresponding to abstinence throughput the entire 12-week trial. Treatment failures were assigned a value of 0. Comparison of NOBWOS values revealed a significant effect of bupropion to facilitate abstinence (P= 0.0176). In the bupropion group, 20% of participants achieved 2 or more weeks EOSA, 14% achieved 6 or more weeks EOSA, and 6% were abstinent throughout the trial; this compares with 7%, 4%, and 1% in the placebo group, respectively. On the basis of the NOBWOS analysis, bupropion seems to effectively facilitate the achievement of abstinence in methamphetamine dependent individuals. PMID- 22070721 TI - Immobilization of quantum dots via conjugated self-assembled monolayers and their application as a light-controlled sensor for the detection of hydrogen peroxide. AB - A light-addressable gold electrode modified with CdS and FePt or with CdS@FePt nanoparticles via an interfacial dithiol linker layer is presented. XPS measurements reveal that trans-stilbenedithiol provides high-quality self assembled monolayers compared to benzenedithiol and biphenyldithiol, in case they are formed at elevated temperatures. The CdS nanoparticles in good electrical contact with the electrode allow for current generation under illumination and appropriate polarization. FePt nanoparticles serve as catalytic sites for the reduction of hydrogen peroxide to water. Advantageously, both properties can be combined by the use of hybrid nanoparticles fixed on the electrode by means of the optimized stilbenedithiol layer. This allows a light-controlled analysis of different hydrogen peroxide concentrations. PMID- 22070722 TI - Isometric muscle training of the spine musculature in patients with spinal bony metastases under radiation therapy. AB - BACKGROUND: Osseous metastatic involvement of the spinal column affects many patients with a primary tumour disease of all entities. The consequences are pain both at rest and under exertion, impairments in going about day-to-day activities, diminished performance, the risk of pathological fractures, and neurological deficits. Palliative percutaneous radiotherapy is one of the therapeutical options available in this connection. The aim of this explorative study is to investigate the feasibility of muscle-training exercises and to evaluate the progression- and fracture-free survival time and the improvement of bone density, as well as to assess other clinical parameters such as pain, quality of life, and fatigue as secondary endpoints. METHODS/DESIGN: This study is a prospective, randomized, monocentre, controlled explorative intervention study in the parallel-group design to determine the multidimensional effects of a course of exercises at first under physiotherapeutic instruction and subsequently performed by the patients independently for strengthening the paravertebral muscles of patients with metastases of the vertebral column parallel to their percutaneous radiotherapy. On the days of radiation treatment the patients in the control group shall be given physical treatment in the form of respiratory therapy and the so-called "hot roll". The patients will be randomized into one of the two groups: differentiated muscle training or physiotherapy with thirty patients in each group. DISCUSSION: The aim of the study is to evaluate the feasibility of the training programme described here. Progression-free and fracture-free survival, improved response to radiotherapy by means of bone density, and clinical parameters such as pain, quality of life, and fatigue constitute secondary study objectives. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01409720. PMID- 22070723 TI - All-time releases of mercury to the atmosphere from human activities. AB - Understanding the biogeochemical cycling of mercury is critical for explaining the presence of mercury in remote regions of the world, such as the Arctic and the Himalayas, as well as local concentrations. While we have good knowledge of present-day fluxes of mercury to the atmosphere, we have little knowledge of what emission levels were like in the past. Here we develop a trend of anthropogenic emissions of mercury to the atmosphere from 1850 to 2008-for which relatively complete data are available-and supplement that trend with an estimate of anthropogenic emissions prior to 1850. Global mercury emissions peaked in 1890 at 2600 Mg yr(-1), fell to 700-800 Mg yr(-1) in the interwar years, then rose steadily after 1950 to present-day levels of 2000 Mg yr(-1). Our estimate for total mercury emissions from human activities over all time is 350 Gg, of which 39% was emitted before 1850 and 61% after 1850. Using an eight-compartment global box-model of mercury biogeochemical cycling, we show that these emission trends successfully reproduce present-day atmospheric enrichment in mercury. PMID- 22070724 TI - The role of protamine amount in the transfection performance of cationic SLN designed as a gene nanocarrier. AB - Cationic solid lipid nanoparticles (SLN) have been recently proposed as non-viral vectors in systemic gene therapy. The aim of this study was to evaluate the effect of the protamine amount used as the transfection promoter in SLN-mediated gene delivery. Three protamine-SLN samples (Pro25, Pro100, and Pro200) prepared by adding increasing amounts of protamine were characterized for their size, zeta potential, and protamine loading level. The samples were evaluated for pDNA complexation ability by gel-electrophoresis analysis and for cytotoxicity and transfection efficiency by using different cell lines (COS-I, HepG2, and Na1300). The size of SLN was ~230 nm and only Pro200 showed few particle aggregates. Unlike the Pro25 sample with the lowest protamine loading level, the others SLN samples (Pro100 and Pro200) exhibited a good ability in complexing pDNA. A cell line dependent cytotoxicity lower than that of the positive control PEI (polyethilenimmine) was observed for all the SLN. Among these, only Pro100, having an intermediate amount of protamine, appeared able to promote pDNA cell transfer, especially in a neuronal cell line (Na1300). In conclusion, the amount of protamine as the transfection promoter in SLN affects not only the gene delivery ability of SLN but also their capacity to transfer genes efficiently to specific cell types. PMID- 22070725 TI - Distinct microbial populations exist in the mucosa-associated microbiota of sub groups of irritable bowel syndrome. AB - BACKGROUND: There is increasing evidence to support a role for the gastrointestinal microbiota in the etiology of irritable bowel syndrome (IBS). Given the evidence of an inflammatory component to IBS, the mucosa-associated microbiota potentially play a key role in its pathogenesis. The objectives were to compare the mucosa-associated microbiota between patients with diarrhea predominant IBS (IBS-D), constipation predominant IBS (IBS-C) and controls using fluorescent in situ hybridization and to correlate specific bacteria groups with individual IBS symptoms. METHODS: Forty-seven patients with IBS (27 IBS-D and 20 IBS-C) and 26 healthy controls were recruited to the study. Snap-frozen rectal biopsies were taken at colonoscopy and bacterial quantification performed by hybridizing frozen sections with bacterial-group specific oligonucleotide probes. KEY RESULTS: Patients with IBS had significantly greater numbers of total mucosa associated bacteria per mm of rectal epithelium than controls [median 218 (IQR - 209) vs 128 (121) P = 0.007], and this was chiefly comprised of bacteroides IBS [69 (67) vs 14 (41) P = 0.001] and Eubacterium rectale-Clostridium coccoides [52 (58) vs 25 (35) P = 0.03]. Analysis of IBS sub-groups demonstrated that bifidobacteria were lower in the IBS-D group than in the IBS-C group and controls [24 (32) vs 54 (88) vs 32 (35) P = 0.011]. Finally, amongst patients with IBS, the maximum number of stools per day negatively correlated with the number of mucosa-associated bifidobacteria (P < 0.001) and lactobacilli (P = 0.002). CONCLUSIONS & INFERENCES: The mucosa-associated microbiota in patients with IBS is significantly different from healthy controls with increases in bacteroides and clostridia and a reduction in bifidobacteria in patients with IBS-D. PMID- 22070726 TI - Evidence-based practice in speech-language pathology curricula: a scoping study. AB - This scoping study investigated how evidence-based practice (EBP) principles are taught in Australian speech-language pathology (SLP) teaching and learning contexts. It explored how Australian SLP university programs: (1) facilitate student learning about the principles of EBP in academic and clinical settings, and (2) self-evaluate their curricula in relation to EBP. The research involved two surveys. Survey 1 respondents were 131 academic staff, program coordinators, and on-campus and off-campus clinical educators. This survey gathered information about EBP teaching and learning in SLP programs as well as future EBP curriculum plans. Survey 2 investigated how clinical educators incorporated EBP into the way they taught clinical decision-making to students. Surveys responses from 85 clinical educators were analysed using descriptive and non-parametric statistics and thematic grouping of open-ended qualitative responses. Both surveys revealed strengths and gaps in integrating EBP into Australian SLP curricula. Perceived strengths were that respondents were positive about EBP, most had EBP training and access to EBP resources. The perceived gaps included the academic staff's perceptions of students' understanding and application of EBP, respondents' understanding of research methodologies, communication and collaboration between academic staff and clinical educators, and a lack of explicit discussion by clinical educators and students of EBP in relation to clients. PMID- 22070727 TI - A phase II trial of the Westmead Program: syllable-timed speech treatment for pre school children who stutter. AB - This report presents a Phase II clinical trial of a syllable-timed speech treatment for early stuttering known as The Westmead Program. Of 17 children recruited, eight children aged between 3-4.5 years (mean 3 years 8 months) completed the treatment. The primary outcome measure was percentage syllables stuttered (%SS) measured from independent, blinded speech assessments of beyond clinic audio recordings. Secondary outcomes were measures of treatment time, speech quality, and parent severity ratings. Dropouts occurred, but at a similar rate to other clinical trials of this nature. For the eight children who completed the treatment, mean pre-treatment stuttering was 6.0%SS and at 12 months post-Stage 2 entry stuttering had decreased to 0.2%SS, representing a mean stuttering reduction of 96%. A large effect size was obtained with a mean of 8.0 clinical hours required for these children to reach Stage 2. Independent listeners judged the everyday speech of all children to be not unnatural in any way. Stuttering reductions were attained with clinical efficiency and simplicity compared to other early stuttering interventions. Further clinical trials development of the treatment is warranted. PMID- 22070728 TI - Vertical gradient in soil temperature stimulates development and increases biomass accumulation in barley. AB - We have detailed knowledge from controlled environment studies on the influence of root temperature on plant performance, growth and morphology. However, in all studies root temperature was kept spatially uniform, which motivated us to test whether a vertical gradient in soil temperature affected development and biomass production. Roots of barley seedlings were exposed to three uniform temperature treatments (10, 15 or 20 degrees C) or to a vertical gradient (20-10 degrees C from top to bottom). Substantial differences in plant performance, biomass production and root architecture occurred in the 30-day-old plants. Shoot and root biomass of plants exposed to vertical temperature gradient increased by 144 respectively, 297%, compared with plants grown at uniform root temperature of 20 degrees C. Additionally the root system was concentrated in the upper 10cm of the soil substrate (98% of total root biomass) in contrast to plants grown at uniform soil temperature of 20 degrees C (86% of total root biomass). N and C concentrations in plant roots grown in the gradient were significantly lower than under uniform growth conditions. These results are important for the transferability of 'normal' greenhouse experiments where generally soil temperature is not controlled or monitored and open a new path to better understand and experimentally assess root-shoot interactions. PMID- 22070729 TI - A single-component liquid-phase hydrogen storage material. AB - The current state-of-the-art for hydrogen storage is compressed H(2) at 700 bar. The development of a liquid-phase hydrogen storage material has the potential to take advantage of the existing liquid-based distribution infrastructure. We describe a liquid-phase hydrogen storage material that is a liquid under ambient conditions (i.e., at 20 degrees C and 1 atm pressure), air- and moisture-stable, and recyclable; releases H(2) controllably and cleanly at temperatures below or at the proton exchange membrane fuel cell waste-heat temperature of 80 degrees C; utilizes catalysts that are cheap and abundant for H(2) desorption; features reasonable gravimetric and volumetric storage capacity; and does not undergo a phase change upon H(2) desorption. PMID- 22070730 TI - Nurses' roles in systematic patient education sessions in psychiatric nursing. AB - The purpose of this study is to gain understanding of nurses' expectations of their roles in systematic patient education in psychiatric inpatient care. Qualitative design was used in the study. The data were collected through interviews with nurses participating in the implementation of systematic patient education (information technology (IT) based patient education n= 14, or conventional patient education n= 16). The data were analysed using inductive content analysis. The analysis showed that nurses had different roles in both IT based and conventional patient education. Nurses acted as learners, advisors, collaborators, teachers or limiters. The nurses tailored the role in each session according to the patients' interest and mental status. We can conclude that nurses working in psychiatric hospitals have different roles in systematic patient education and they are ready and willing to tailor their roles according to patients' individual needs. Information technology should be adopted without delay as a new treatment method in daily practice in psychiatric services. It has potential to support equality between patient and nurse in secluded environments. PMID- 22070731 TI - Development of fetal intestinal length during 2nd-trimester in normal and pathologic pregnancies. AB - Linear growth of the human fetal gastrointestinal tract is not often discussed in the literature, and little is known about the effects of chromosomal abnormalities and intrauterine growth restriction (IUGR) on intestinal length, especially during the 2nd trimester. Accurate evaluation of intestinal length and knowledge of normal and reference values are of clinical importance. For example, intestinal resection may be necessary in preterm infants with necrotizing enterocolitis or mid-gut volvulus, and the surgeon should use data to be judicious in the amount removed. Linear measurements are essential in evaluating fetal development ultrasonographically and are an integral part of the postmortem examination. The intestinal lengths of 203 2nd-trimester fetuses and premature infants were measured. Small intestine length (SIL), colon length (CL), total bowel length (TBL; TBL = SIL + CL), and the length of the appendix (AL) increased with gestational age. No differences between the genders were observed. Colon length increased secondary to maceration, but no such effects were shown on SIL, TBL, or AL. No differences were shown in relation to IUGR. Small intestine length, CL, and TBL, but not AL, were shorter in fetuses with trisomy 21. Appendix length was not affected by any of the studied factors. We propose that the measurement of the length of the appendix may be used as an additional parameter for the postmortem evaluation of gestational age. Furthermore, its assessment may have potential as an ultrasonographic indicator of gestational age, particularly for the 2nd trimester. PMID- 22070732 TI - Embryonic stem cell-derived T cells induce lethal graft-versus-host disease and reject allogenic skin grafts upon thymic selection. AB - Efficient differentiation of embryonic stem cells (ESC) into hematopoietic progenitor cells (HPCs) is crucial for the establishment of stem cell-based therapies targeting the treatment of immunological and hematological disorders. However, so far, it has not been possible to induce long-term survival of murine ESC-derived HPCs without the overexpression of HoxB4, a homeobox transcription factor that confers self-renewal properties to hematopoietic cells. Yet it has not been feasible to generate T cells from HoxB4-expressing HPCs, a problem that has been attributed to HoxB4. Here, we show that Notch1 signaling in HoxB4 transduced ESCs leads to efficient derivation of T cells that survive long term. These T cells display a normal T-cell Vbeta repertoire, respond to mitogen stimulation and induce lethal graft-versus-host disease. Thymic selection in fetal thymic organ cultures (FTOCs) allowed negative selection and generation of T cells tolerant to 'self' and capable of rejecting MHC-mismatched skin allografts. Our data show that ESC-derived T cells, despite high expression of HoxB4, are fully immunocompetent. PMID- 22070733 TI - Does individual placement and support really 'reflect client goals'? AB - Individual placement and support (IPS) is considered the only evidence-based practice available for providing vocational support within secondary mental health services. Clients are supported into and during competitive employment, with proponents claiming IPS 'reflects client goals' because most service users want to work. The idea that work improves mental health is also involved in promoting IPS in the U.K. This paper examines the evidential basis for these claims in policy documents and cited research. It additionally draws upon qualitative research in representing the value, meaning and challenges of working described by service users, while briefly considering the U.K. socio-economic context for IPS implementation. Statistical claims that most unemployed service users want to work are found misleadingly applied to IPS because only a minority say they want competitive employment. Discussion centres on the power interests such statistics serve and their role in underpinning the relevance of IPS randomized control trials. Assertions that work improves mental health are found confusing as a result of use of a dual continua model of mental illness and mental health. The internalized moral basis for work acting as a seemingly healthy 'normalization' experience is suggested as paradoxically feeding self stigma in those who feel they cannot work. PMID- 22070734 TI - Computational studies on ethylene addition to nickel bis(dithiolene). AB - The density functionals B3LYP, B3PW91, BMK, HSE06, LC-omegaPBE, M05, M06, O3LYP, TPSS, omega-B97X, and omega-B97XD are used to optimize key transition states and intermediates for ethylene addition to Ni(edt)(2) (edt = S(2)C(2)H(2)). The efficacy of the basis sets 6-31G**, 6-31++G**, cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ is also examined. The geometric parameters optimized with different basis sets and density functionals are similar and agree well with experimental values. The omega-B97XD functional gives relative energies closest to those from CCSD, while M06 and HSE06 yield results close to those from CCSD(T). CASSCF and CASSCF-PT2 calculation results are also given. Variation of the relative energies from different density functionals appears to arise, in part, from the multireference character of this system, as confirmed by the T1 diagnostic and CASSCF calculations. PMID- 22070735 TI - The image of you: constructing nursing identities in YouTube. AB - AIM: This article is a report on a descriptive study of nursing identity as constructed in the Web 2.0 site YouTube. BACKGROUND: Public images of the nurse carry stereotypes that rely on the taken for granted gender category of the nurse as woman. Nursing images represent a form of public discourse that has the capacity to construct nursing identity. METHODS: Critical discourse analysis was used to describe, analyse and explain how nurse and nursing identity were constructed in a purposive sample of ten video clips accessed on 17 and 18 July 2010. RESULTS: The ten most-viewed videos depicting the nurse and nursing on YouTube offered narratives that constructed three distinct nursing identity types, namely nurse as 'a skilled knower and doer', nurse as 'a sexual plaything' and nurse as 'a witless incompetent' individual. CONCLUSION: Nursing identities recoverable from the texts of YouTube images propagate both favourable and derogatory nursing stereotypes. To mitigate the effects of unfavourable nursing stereotypes in such areas as interprofessional working and clinical decision making, nursing professional bodies need to act to protect the profession from unduly immoderate representations of the nurse and to support nurses in their efforts to maximize opportunities afforded by YouTube to promote a counter discourse. PMID- 22070737 TI - Community mental health nurses' perspectives of recovery-oriented practice. AB - Recovery-oriented practice, an approach aligned towards the service user perspective, has dominated the mental health care arena. Numerous studies have explored service users' accounts of the purpose, meaning and importance of 'recovery'; however, far less is known about healthcare staff confidence in its application to care delivery. A self-efficacy questionnaire and content analysis of nursing course documents were used to investigate a cohort of community mental health nurses' recovery-oriented practice and to determine the extent to which the current continuing professional development curriculum met their educational needs in this regard. Twenty-three community mental health nurses completed a self-efficacy questionnaire and 28 course documents were analysed. The findings revealed high levels of nurses' confidence in their understanding and ability to apply the recovery model and low levels of confidence were found in areas of social inclusion. The content analysis found only one course document that used the whole term 'recovery model'. The findings suggest a gap in the nurses' perceived ability and confidence in recovery-oriented practice with what is taught academically. Hence, nursing education needs to be more explicitly focused on the recovery model and its application to care delivery. PMID- 22070736 TI - New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia. AB - BACKGROUND: Maternal immunization against low-frequency, platelet (PLT)-specific antigens is being recognized with increasing frequency as a cause of neonatal alloimmune thrombocytopenia (NAIT). STUDY DESIGN AND METHODS: Serologic and molecular studies were performed on PLTs and DNA from two families in which an infant was born with severe thrombocytopenia not attributable to maternal immunization against known PLT-specific alloantigens. RESULTS: Antibodies reactive only with paternal PLTs were identified in each mother using flow cytometry and solid-phase assays. Unique mutations encoding amino acid substitutions K164T in glycoprotein (GP)IIb (Case 1) and R622W in GPIIIa (Case 2) were identified in paternal DNA and in DNA from the affected infants. Each maternal antibody recognized recombinant GPIIb/IIIa mutated to contain the polymorphisms identified in the corresponding father. None of 100 unselected normal subjects possessed these paternal mutations. CONCLUSIONS: Severe NAIT observed in the affected infants was caused by maternal immunization against previously unrecognized, low-frequency antigens created by amino acid substitutions in GPIIb/IIIa (alpha(IIb) /beta(3) integrin). A search should be conducted for novel paternal antigens in cases of apparent NAIT not explained on the basis of maternal-fetal incompatibility for known human PLT antigens. PMID- 22070738 TI - Modeling the dementia epidemic. AB - The incidence of dementia increases steeply with age in older people, although from the tenth decade the slope may be smoother, perhaps reflecting different pathological processes in the oldest old. The prevalence depends upon interaction of age with other factors (e.g., comorbidities, genetic or environmental factors) that in turn are subject to change. If onset of dementia could be postponed by modulating its risk factors, this could significantly affect its incidence. Analysis of risk and protection factors should take into account the critical period during which these factors play a role. For example, the impact of education and diabetes mellitus occurs in early- and midlife, respectively, while maintaining optimal physical and mental activity and controlling vascular factors later in life may slow the rate of cognitive decline. Modifying factors need to be evaluated for different clinical groups, taking into account genetic background, age, and duration at exposure. The aim of the present article is to try to take stock of epidemiological data concerning factors affecting the prevalence of dementia and predict future developments, as well as to look for possible interventions that could affect outcome. PMID- 22070739 TI - Semiparametric frailty models for clustered failure time data. AB - We consider frailty models with additive semiparametric covariate effects for clustered failure time data. We propose a doubly penalized partial likelihood (DPPL) procedure to estimate the nonparametric functions using smoothing splines. We show that the DPPL estimators could be obtained from fitting an augmented working frailty model with parametric covariate effects, whereas the nonparametric functions being estimated as linear combinations of fixed and random effects, and the smoothing parameters being estimated as extra variance components. This approach allows us to conveniently estimate all model components within a unified frailty model framework. We evaluate the finite sample performance of the proposed method via a simulation study, and apply the method to analyze data from a study of sexually transmitted infections (STI). PMID- 22070740 TI - Welcome to the neighbourhood: interspecific genotype by genotype interactions in Solidago influence above- and belowground biomass and associated communities. AB - Intra- and interspecific plant-plant interactions are fundamental to patterns of community assembly and to the mixture effects observed in biodiversity studies. Although much research has been conducted at the species level, very little is understood about how genetic variation within and among interacting species may drive these processes. Using clones of both Solidago altissima and Solidago gigantea, we found that genotypic variation in a plant's neighbours affected both above- and belowground plant traits, and that genotype by genotype interactions between neighbouring plants impacted associated pollinator communities. The traits for which focal plant genotypic variation explained the most variation varied by plant species, whereas neighbour genotypic variation explained the most variation in coarse root biomass. Our results provide new insight into genotypic and species diversity effects in plant-neighbour interactions, the extended consequences of diversity effects, and the potential for evolution in response to competitive or to facilitative plant-neighbour interactions. PMID- 22070741 TI - The use of ice-lollies for pain relief post-paediatric tonsillectomy. A single blinded, randomised, controlled trial. AB - OBJECTIVES: To assess whether the use of ice-lollies after tonsillectomy with or without adenoidectomy in children aged 2-12 reduces pain in the immediate postoperative period. DESIGN: A prospective, randomised, single-blinded study design consisting of two groups with an intention to treat analysis. SETTING: Tertiary referral centre. PARTICIPANTS: Children aged 2-12 undergoing tonsillectomy with or without adenoidectomy. MAIN OUTCOME MEASURES: Pain assessment by nursing staff in the form of the validated modified Children's Hospital of Eastern Ontario Pain Scale at 15, 30 and 60 min and 4 h. RESULTS: Ninety-two patients were recruited into the study with 46 allocated to receive an ice-lolly and 41 not to receive an ice-lolly after exclusion of those with incomplete data. The two groups were comparable for number, age, sex and diagnosis. The pain score at every time interval was lower in the group that had received the ice-lolly compared with the group that had not. This was statistically significant at 30 (P = 0.008) and 60 min (P = 0.049). CONCLUSION: Our data suggest that ice-lollies are a cheap, effective and safe method of reducing postoperative pain up to one hour following paediatric tonsillectomy. PMID- 22070742 TI - Fiber containment for improved laboratory handling and uniform nanocoating of milligram quantities of carbon nanotubes by atomic layer deposition. AB - The presence of nanostructured materials in the workplace is bringing attention to the importance of safe practices for nanomaterial handling. We explored novel fiber containment methods to improve the handling of carbon nanotube (CNT) powders in the laboratory while simultaneously allowing highly uniform and controlled atomic layer deposition (ALD) coatings on the nanotubes, down to less than 4 nm on some CNT materials. Moreover, the procedure yields uniform coatings on milligram quantities of nanotubes using a conventional viscous flow reactor system, circumventing the need for specialized fluidized bed or rotary ALD reactors for laboratory-scale studies. We explored both fiber bundles and fiber baskets as possible containment methods and conclude that the baskets are more suitable for coating studies. An extended precursor and reactant dose and soak periods allowed the gases to diffuse through the fiber containment, and the ALD coating thickness scaled linearly with the number of ALD cycles. The extended dose period produced thicker coatings compared to typical doses on CNT controls not encased in the fibers, suggesting some effects due to the extended reactant dose. Film growth was compared on a range of single-walled NTs, double-walled NTs, and acid-functionalized multiwalled NTs, and we found that ultrathin coatings were most readily controlled on the multiwalled NTs. PMID- 22070743 TI - Metal mesh scaffold for tissue engineering of membranes. AB - Engineering of the membrane-like tissue structures to be utilized in highly dynamic loading environments such as the cardiovascular system has been a challenge in the past decade. Scaffolds are critical components of the engineered tissue membranes and allow them being formed in vitro and remain secure in vivo when implanted in the body. Several approaches have been taken to develop scaffolds for tissue membranes. However, all methods entail limitations due to structural vulnerability, short-term functionality, and mechanical properties of the resulted membrane constructs. To overcome these issues, we have developed a novel hybrid scaffold made of an extra thin layer of metal mesh tightly enclosed by biological matrix components. This approach retains all the advantages of using biological scaffolds while developing a strong extracellular matrix that can stand various types of loads after implantation inside the body. PMID- 22070745 TI - Financial and social impact of supporting a haematological cancer survivor. AB - Support persons of haematological cancer survivors may be faced with unique challenges due to the course of these diseases and the treatments required. This study aimed to examine the social and financial impacts associated with their role. Eight hundred adult survivors of haematological cancer within 3 years of diagnosis were invited via an Australian state population-based cancer registry to complete a survey. Survivors were mailed two questionnaire packages, one for themselves and one for their primary support person. Non-respondents were mailed reminders via the survivor after 3 weeks. One hundred and eighty-two support persons completed the questionnaire (85% response rate). Of these, 67 (46%) support persons reported having at least one personal expense and 91 (52%) experienced at least one financial impact. Male support persons and support persons of survivors in active treatment reported experiencing more personal expenses than other support persons. Older participants reported fewer financial consequences. A greater number of social impacts were reported by those born outside Australia, those who had to relocate for treatment and support persons of survivors in active treatment. Future research should focus on practical solutions to reducing these impacts on support persons. PMID- 22070744 TI - Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial. AB - BACKGROUND: Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. METHODS/DESIGN: The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. DISCUSSION: This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. PMID- 22070746 TI - Deregressed EBV as the response variable yield more reliable genomic predictions than traditional EBV in pure-bred pigs. AB - BACKGROUND: Genomic selection can be implemented by a multi-step procedure, which requires a response variable and a statistical method. For pure-bred pigs, it was hypothesised that deregressed estimated breeding values (EBV) with the parent average removed as the response variable generate higher reliabilities of genomic breeding values than EBV, and that the normal, thick-tailed and mixture distribution models yield similar reliabilities. METHODS: Reliabilities of genomic breeding values were estimated with EBV and deregressed EBV as response variables and under the three statistical methods, genomic BLUP, Bayesian Lasso and MIXTURE. The methods were examined by splitting data into a reference data set of 1375 genotyped animals that were performance tested before October 2008, and 536 genotyped validation animals that were performance tested after October 2008. The traits examined were daily gain and feed conversion ratio. RESULTS: Using deregressed EBV as the response variable yielded 18 to 39% higher reliabilities of the genomic breeding values than using EBV as the response variable. For daily gain, the increase in reliability due to deregression was significant and approximately 35%, whereas for feed conversion ratio it ranged between 18 and 39% and was significant only when MIXTURE was used. Genomic BLUP, Bayesian Lasso and MIXTURE had similar reliabilities. CONCLUSIONS: Deregressed EBV is the preferred response variable, whereas the choice of statistical method is less critical for pure-bred pigs. The increase of 18 to 39% in reliability is worthwhile, since the reliabilities of the genomic breeding values directly affect the returns from genomic selection. PMID- 22070747 TI - ALAS1 gene expression is down-regulated by Akt-mediated phosphorylation and nuclear exclusion of FOXO1 by vanadate in diabetic mice. AB - Porphyrias are diseases caused by partial deficiencies of haem biosynthesis enzymes. Acute porphyrias are characterized by a neuropsychiatric syndrome with intermittent induction of hepatic ALAS1 (delta-aminolaevulinate synthase 1), the first and rate-limiting enzyme of the haem pathway. Acute porphyria attacks are usually treated by the administration of glucose; its effect is apparently related to its ability to inhibit ALAS1 by modulating insulin plasma levels. It has been shown that insulin blunts hepatocyte ALAS1 induction, by disrupting the interaction of FOXO1 (forkhead box O1) and PGC-1alpha (peroxisome-proliferator activated receptor gamma co-activator 1alpha). We evaluated the expression of ALAS1 in a murine model of diabetes and determined the effects of the insulinomimetic vanadate on the enzyme regulation to evaluate its potential for the treatment of acute porphyria attacks. Both ALAS1 mRNA and protein content were induced in diabetic animals, accompanied by decreased Akt phosphorylation and increased nuclear FOXO1, PGC-1alpha and FOXO1-PGC-1alpha complex levels. Vanadate reversed ALAS1 induction, with a concomitant PI3K (phosphoinositide 3 kinase)/Akt pathway activation and subsequent reduction of nuclear FOXO1, PGC 1alpha and FOXO1-PGC-1alpha complex levels. These findings support the notion that the FOXO1-PGC-1alpha complex is involved in the control of ALAS1 expression and suggest further that a vanadate-based therapy could be beneficial for the treatment of acute porphyria attacks. PMID- 22070748 TI - Interference of silver, gold, and iron oxide nanoparticles on epidermal growth factor signal transduction in epithelial cells. AB - Metallic nanomaterials, including silver, gold, and iron oxide, are being utilized in an increasing number of fields and specialties. The use of nanosilver as an antimicrobial agent is becoming ever-more common, whereas gold and iron oxide nanomaterials are frequently utilized in the medical field due to their recognized "biocompatibility". Numerous reports have examined the general toxicity of these nanomaterials; however, little data exists on how the introduction of these nanomaterials, at nontoxic levels, affects normal cellular processes. In the present study the impact of low levels of 10 nm silver (Ag-NP), gold (Au-NP), and iron oxide nanoparticles (SPION) on epidermal growth factor (EGF) signal transduction within the human epithelial cell line, A-431, was investigated. Following a biocompatibility assessment, the nanoparticle-induced interference at four specific targets within the EGF signaling process was evaluated: (1) nanoparticle-EGF association, (2) Akt and Erk phosphorylation, (3) Akt activity, and (4) EGF-dependent gene regulation. For all tested nanoparticles, following cellular exposure, a disruption in the EGF signaling response transpired; however, the metallic composition determined the mechanism of alteration. In addition to inducing high quantities of ROS, Ag-NPs attenuated levels of Akt and Erk phosphorylation. Au-NPs were found to decrease EGF dependent Akt and Erk phosphorylation as well as inhibit Akt activity. Lastly, SPIONs produced a strong alteration in EGF activated gene transcription, with targeted genes influencing cell proliferation, migration, and receptor expression. These results demonstrate that even at low doses, introduction of Ag NPs, Au-NPs, and SPIONs impaired the A-431 cell line's response to EGF. PMID- 22070749 TI - Examining the relationship between risk assessment and risk management in mental health. AB - Thorough risk assessment helps in developing risk management plans that minimize risks that can impede mental health patients' recovery. Department of Health policy states that risk assessments and risk management plans should be inextricably linked. This paper examines their content and linkage within one Trust. Four inpatient wards for working age adults (18-65 years) in a large mental health Trust in England were included in the study. Completed risk assessment forms, for all patients in each inpatient ward were examined (n= 43), followed by an examination of notes for the same patients. Semi-structured interviews took place with ward nurses (n= 17). Findings show much variability in the amount and detail of risk information collected by nurses, which may be distributed in several places. Gaps in the risk assessment and risk management process are evident, and a disassociation between risk information and risk management plans is often present. Risk information should have a single location so that it can be easily found and updated. Overall, a more integrated approach to risk assessment and management is required, to help patients receive timely and appropriate interventions that can reduce risks such as suicide or harm to others. PMID- 22070750 TI - Few-layered graphene oxide nanosheets as superior sorbents for heavy metal ion pollution management. AB - Graphene has attracted multidisciplinary study because of its unique physicochemical properties. Herein, few-layered graphene oxide nanosheets were synthesized from graphite using the modified Hummers method, and were used as sorbents for the removal of Cd(II) and Co(II) ions from large volumes of aqueous solutions. The effects of pH, ionic strength, and humic acid on Cd(II) and Co(II) sorption were investigated. The results indicated that Cd(II) and Co(II) sorption on graphene oxide nanosheets was strongly dependent on pH and weakly dependent on ionic strength. The abundant oxygen-containing functional groups on the surfaces of graphene oxide nanosheets played an important role on Cd(II) and Co(II) sorption. The presence of humic acid reduced Cd(II) and Co(II) sorption on graphene oxide nanosheets at pH < 8. The maximum sorption capacities (C(smax)) of Cd(II) and Co(II) on graphene oxide nanosheets at pH 6.0 +/- 0.1 and T = 303 K were about 106.3 and 68.2 mg/g, respectively, higher than any currently reported. The thermodynamic parameters calculated from temperature-dependent sorption isotherms suggested that Cd(II) and Co(II) sorptions on graphene oxide nanosheets were endothermic and spontaneous processes. The graphene oxide nanosheets may be suitable materials in heavy metal ion pollution cleanup if they are synthesized in large scale and at low price in near future. PMID- 22070751 TI - An ATP signalling pathway in plant cells: extracellular ATP triggers programmed cell death in Populus euphratica. AB - We elucidated the extracellular ATP (eATP) signalling cascade active in programmed cell death (PCD) using cell cultures of Populus euphratica. Millimolar amounts of eATP induced a dose- and time-dependent reduction in viability, and the agonist-treated cells displayed hallmark features of PCD. eATP caused an elevation of cytosolic Ca(2+) levels, resulting in Ca(2+) uptake by the mitochondria and subsequent H(2) O(2) accumulation. P. euphratica exhibited an increased mitochondrial transmembrane potential, and cytochrome c was released without opening of the permeability transition pore over the period of ATP stimulation. Moreover, the eATP-induced increase of intracellular ATP, essential for the activation of caspase-like proteases and subsequent PCD, was found to be related to increased mitochondrial transmembrane potential. NO is implicated as a downstream component of the cytosolic Ca(2+) concentration but plays a negligible role in eATP-stimulated cell death. We speculate that ATP binds purinoceptors in the plasma membrane, leading to the induction of downstream intermediate signals, as the proposed sequence of events in PCD signalling was terminated by the animal P2 receptor antagonist suramin. PMID- 22070752 TI - Low molecular weight chitosan-coated liposomes for ocular drug delivery: in vitro and in vivo studies. AB - In this study, low molecular weight chitosan coated liposomes (LCHL) were designed and prepared for ocular drug delivery, the coating mechanism was studied, and in vitro and in vivo characterization was conducted. The effects of molecular weight and concentration of low molecular weight chitosan on the liposomal coating were studied. The numeric relations between coating variables and coating efficiency were established using a mathematical model. Morphology of LCHL was examined by transmission electron microscopy (TEM). Cytotoxicity and cell internalization of FITC-BSA labeled LCHL in a rabbit conjunctival epithelium (RCE) cell line were studied. Cyclosporin A (CsA) was encapsulated as a model drug, and in vitro drug release and in vivo drug absorption were investigated. LCHL demonstrated low toxicity to RCE cells. In vitro drug release measurement showed that LCHL had a delayed release profile compared with non-coated liposomes. In vivo study in rabbits showed that the concentrations of CsA in cornea, conjunctiva, and sclera were remarkably increased by LCHL. In conclusion, LCHL might be a potential ocular drug carrier with characteristics such as prolonged drug retention, enhanced drug permeation, and biocompatibility. PMID- 22070756 TI - Intrauterine fetal death of a monochorionic twin with peripheral pulmonary infarcts: potential thromboembolic events following death of co-twin. AB - In utero fetal lung infarction has rarely been reported. We present a case of intrauterine lung infarction in a 28-3/7 weeks' gestation monochorionic twin following intrauterine fetal demise of the co-twin at 20 weeks. This case highlights the potential for thromboembolic events (TBEs) associated with monochorionic gestations to include pulmonary TBE and infarction among the risks for fetal morbidity and mortality. PMID- 22070757 TI - Patients of parish nurses experience renewed spiritual identity: a grounded theory study. AB - AIM: This article is a report of a study of the process that patients of parish nurses experience when they are provided spiritual care in Christian churches, a context where patients and nurses share a common set of values. BACKGROUND: Many studies have explored hospitalized patients' views and experiences of spiritual care. However, little is known about the spiritual changes that patients experience as they receive care from parish nurses. METHODS: The grounded theory method was used to explore what patients of the parish nurses experienced in spiritual care. Half of the participants were interviewed in 1999-2001 at the time of the parish nurse interviews, and half in 2005. Audiotapes were transcribed verbatim. Constant comparative methods were used to analyse the incidents of receiving spiritual care. FINDINGS: Theoretical memos described how the 'main concern' of the patients to resolve their health challenge resulted in changes to their spiritual identity. Phases in the change process included: facing a health challenge, finding a safe place, releasing burdens, changing perspectives and joining or rejoining the family of faith. The essence the patients experienced was an enhanced understanding of who they were in God/Christ. CONCLUSION: The patient's spiritual challenge is to re-conceptualize the self (as one who is known and loved by God) in the context of a particular health challenge. Spiritual care helps them find a new equilibrium in faith. PMID- 22070758 TI - Microwave spectra and gas phase structural parameters for N-hydroxypyridine-2(1H) thione. AB - The microwave spectrum for N-hydroxypyridine-2(1H)-thione (pyrithione) was measured in the frequency range 6-18 GHz, providing accurate rotational constants and nitrogen quadrupole coupling strengths for three isotopologues, C(5)H(4)(32)S(14)NOH, C(5)H(4)(32)S(14)NOD, and C(5)H(4)(34)S(14)NOH. Pyrithione was found to be in a higher concentration in the gas phase than the other tautomer, 2-mercaptopyridine-N-oxide (MPO). Microwave spectroscopy is best suited to determine which structure predominates in the gas phase. The measured rotational constants were used to accurately determine the coordinates of the substituted atoms and provided sufficient data to determine some of the important structural parameters for pyrithione, the only tautomer observed in the present work. The spectra were obtained using a pulsed-beam Fourier transform microwave spectrometer, with sufficient resolution to allow accurate measurements of the (14)N nuclear quadrupole hyperfine interactions. Ab initio calculations provided structural parameters and quadrupole coupling strengths that are in very good agreement with measured values. The experimental rotational constants for the parent compound are A = 3212.10(1), B = 1609.328(7), and C = 1072.208(6) MHz, yielding the inertial defect Delta(0) = -0.023 amu.A(2) for the C(5)H(4)(32)S(14)NOH isotopologue. The observed near zero inertial defect clearly indicates a planar structure. The least-squares fit structural analysis yielded the experimental bond lengths R(O-H) = 0.93(2) A, R(C-S) = 1.66(2) A, and angle (N-O-H) = 105(4) degrees for the ground state structure. PMID- 22070759 TI - Attitudes of relatives and staff towards family intervention in forensic services using Q methodology. AB - Attitudes about family interventions have been identified as a possible reason for the poor implementation of such treatments. The current study used Q methodology to investigate the attitudes of relatives of forensic service users and clinical staff towards family interventions in medium secure forensic units, particularly when facilitated by a web camera. Eighteen relatives and twenty-nine staff completed a sixty-one item Q sort to obtain their idiosyncratic views about family intervention. The results indicated that relatives and staff mostly held positive attitudes towards family intervention. Relatives showed some uncertainty towards family intervention that may reflect the lack of involvement they receive from the forensic service. Staff highlighted key barriers to successful implementation such as lack of dedicated staff time for family work and few staff adequately trained in family intervention. Despite agreement with the web-based forensic family intervention technique and its benefits, both staff and relatives predicted problems in the technique. PMID- 22070760 TI - Cointegration methodology for psychological researchers: An introduction to the analysis of dynamic process systems. AB - Longitudinal data analysis focused on internal characteristics of a single time series has attracted increasing interest among psychologists. The systemic psychological perspective suggests, however, that many long-term phenomena are mutually interconnected, forming a dynamic system. Hence, only multivariate methods can handle such human dynamics appropriately. Unlike the majority of time series methodologies, the cointegration approach allows interdependencies of integrated (i.e., extremely unstable) processes to be modelled. This advantage results from the fact that cointegrated series are connected by stationary long run equilibrium relationships. Vector error-correction models are frequently used representations of cointegrated systems. They capture both this equilibrium and compensation mechanisms in the case of short-term deviations due to developmental changes. Thus, the past disequilibrium serves as explanatory variable in the dynamic behaviour of current variables. Employing empirical data from cognitive psychology, psychosomatics, and marital interaction research, this paper describes how to apply cointegration methods to dynamic process systems and how to interpret the parameters under investigation from a psychological perspective. PMID- 22070761 TI - Suboptimal light conditions negatively affect the heterotrophy of Planktothrix rubescens but are beneficial for accompanying Limnohabitans spp. AB - We examined the effect of light on the heterotrophic activity of the filamentous cyanobacterium Planktothrix rubescens and on its relationship with the accompanying bacteria. In situ leucine uptake by bacteria and cyanobacteria was determined in a subalpine mesotrophic lake, and natural assemblages from the zone of maximal P. rubescens abundances were incubated for 2 days at contrasting light regimes (ambient, 100* increased, dark). Planktothrix rubescens from the photic zone of the lake incorporated substantially more leucine, but some heterotrophic activity was maintained in filaments from the hypolimnion. Exposure of cyanobacteria to increased irradiance or darkness resulted in significantly lower leucine incorporation than at ambient light conditions. Highest abundances and leucine uptake of Betaproteobacteria from the genus Limnohabitans were found in the accompanying microflora at suboptimal irradiance levels for P. rubescens or in dark incubations. Therefore, two Limnohabitans strains (representing different species) were co-cultured with axenic P. rubescens at different light conditions. The abundances and leucine incorporation rates of both strains most strongly increased at elevated irradiance levels, in parallel to a decrease of photosynthetic pigment fluorescence and the fragmentation of cyanobacterial filaments. Our results suggest that Limnohabitans spp. in lakes might profit from the presence of physiologically stressed P. rubescens. PMID- 22070762 TI - Nursing academicians' attitudes towards work life and their personality traits. AB - The purpose of this study was to determine the relationship between attitudes of nursing academicians towards job and organization and their personality traits. The research included 287 nursing academicians who worked in 14 School of Nurses in the Universities of Turkey. A descriptive information form, Job and Organization Related Attitude Scale and Temperament and Character Inventory were used as data collection tools. It has been determined that attitudes of nursing academicians towards job and organization and their personality traits depended upon socio-economic status, working year, academic title, the temperament feature of novelty seeking and persistence, and the character feature of self directedness and cooperativeness. PMID- 22070764 TI - Free amino acid and phenolic contents and antioxidative and cancer cell inhibiting activities of extracts of 11 greenhouse-grown tomato varieties and 13 tomato-based foods. AB - Tomato (Solanum lycopersicum) plants synthesize nutrients, pigments, and bioactive compounds that benefit nutrition and human health. The nature and concentrations of these compounds are strongly influenced by varietal factors such as size and color as well as by processing. To better understand how these factors affect the concentration of nutrients and bioactive compounds, we analyzed 11 Korean tomato varieties grown under the same greenhouse conditions and 13 processed commercial tomato products for free amino acids and amino acid metabolites by HPLC, for individual phenolics by HPLC-MS, for total phenolics by the Folin-Ciocalteu method, for antioxidative activity by the FRAP and DPPH methods, and for cancer cell-inhibiting effects by the MTT assay. We also determined the protein content of the tomatoes by an automated Kjeldahl method. The results show that there is a broad range of bioactive compounds across tomato varieties and products. Small tomatoes had higher contents of bioactive compounds than the large ones. The content of phenolic compounds of processed products was lower than that of fresh tomatoes. Tomato extracts promoted growth in normal liver (Chang) cells, had little effect in normal lung (Hel299) cells, mildly inhibited growth of lung cancer (A549) cells, and first promoted and then, at higher concentrations, inhibited growth in lymphoma (U937) cells. The relationship of cell growth to measured constituents was not apparent. Dietary and health aspects of the results are discussed. PMID- 22070765 TI - Odds ratios simplified. PMID- 22070766 TI - Optimisation and validation of a quantitative and confirmatory LC-MS method for multi-residue analyses of beta-lactam and tetracycline antibiotics in bovine muscle. AB - A multi-residue method for the determination of the beta-lactam antibiotics ampicillin, cefazolin, cloxacillin, dicloxacillin, nafcillin, oxacillin, penicillin G, penicillin V and the tetracyclines chlotetracycline, tetracycline and oxytetracycline was optimised and validated in bovine muscle. The method is based on the extraction of the residues from muscle using water/acetonitrile (2/8, v/v) with subsequent use of dispersive solid-phase C18 and hexane for purification. Extracts were analysed using ultra-performance liquid chromatography (UPLC-MS/MS) coupled with the mass spectrometer in positive electrospray ionisation mode (ESI+) for all analytes. The method was validated according to the requirements of European Commission Decision 2002/657/EC. The validation results were obtained within the MRL range of 0-1.5 of the MRL, with recoveries varying from 90% to 110% and CV < 20% (n = 54), except for cloxacillin, dicloxacillin and nafcillin. However, matrix interference was observed. The decision limit (CCalpha) ranged from 10% to 15% of the MRL. The uncertainty measurement was estimated based on both bottom-up and top-down strategies and the uncertainty values were found to be lower than 20% of the MRL. The method has a simple extraction procedure whereby analytes are separated with reasonable resolutions in a single 11-min chromatographic run. According to the validation results, this method is suitable for monitoring beta-lactams and tetracyclines according to National Program for Residue and Contaminant Control - Brazil (NPRC-Brazil) in bovine muscle. PMID- 22070763 TI - Molecular techniques in the biotechnological fight against halogenated compounds in anoxic environments. AB - Microbial treatment of environmental contamination by anthropogenic halogenated organic compounds has become popular in recent decades, especially in the subsurface environments. Molecular techniques such as polymerase chain reaction based fingerprinting methods have been extensively used to closely monitor the presence and activities of dehalogenating microbes, which also lead to the discovery of new dehalogenating bacteria and novel functional genes. Nowadays, traditional molecular techniques are being further developed and optimized for higher sensitivity, specificity, and accuracy to better fit the contexts of dehalogenation. On the other hand, newly developed high throughput techniques, such as microarray and next-generation sequencing, provide unsurpassed detection ability, which has enabled large-scale comparative genomic and whole-genome transcriptomic analysis. The aim of this review is to summarize applications of various molecular tools in the field of microbially mediated dehalogenation of various halogenated organic compounds. It is expected that traditional molecular techniques and nucleic-acid-based biomarkers will still be favoured in the foreseeable future because of relative low costs and high flexibility. Collective analyses of metagenomic sequencing data are still in need of information from individual dehalogenating strains and functional reductive dehalogenase genes in order to draw reliable conclusions. PMID- 22070767 TI - Hopelessness and social comparison in Turkish adolescent with visual impairment. AB - The purpose of this study was to determine visually impaired adolescents' level of hopelessness and how they perceive of themselves socially compared to other individuals. Another purpose of this study was to look for relationships between hopelessness and social comparison in adolescents with visual impairment. The research population was comprised of 130 students at a secondary school for the visually impaired in Istanbul, Turkey. Our study demonstrated a weak relationship between social comparison and hopelessness (r=-0.46, P < 0.000). The mean hopelessness score for the adolescents with visual impairment was 4.59 +/- 3.12 (girls: 4.23 +/- 3.10; boys: 4.83 +/- 3.11) and social comparison score was 87.50 +/- 11.19 (girls: 88.67 +/- 11.62; boys: 86.60 +/- 10.85). Hopelessness and social comparison were not affected by being blind from birth compared to later or from being a full-time boarding student compared to being a day student. The hopeless (Beck Hopelessness Scale score >= 9) adolescents' social comparison scores were found lower than hopeful ones' scores (P < 000). Factors affecting hopelessness and social comparison were feelings about their father, teacher and school. PMID- 22070768 TI - Measuring walking within and outside the neighborhood in Chinese elders: reliability and validity. AB - BACKGROUND: Walking is a preferred, prevalent and recommended activity for aging populations and is influenced by the neighborhood built environment. To study this influence it is necessary to differentiate whether walking occurs within or outside of the neighborhood. The Neighborhood Physical Activity Questionnaire (NPAQ) collects information on setting-specific physical activity, including walking, inside and outside one's neighborhood. While the NPAQ has shown to be a reliable measure in adults, its reliability in older adults is unknown. Additionally its validity and the influence of type of neighborhood on reliability and validity have yet to be explored. METHODS: The NPAQ walking component was adapted for Chinese speaking elders (NWQ-CS). Ninety-six Chinese elders, stratified by social economic status and neighborhood walkability, wore an accelerometer and completed a log of walks for 7 days. Following the collection of valid data the NWQ-CS was interviewer-administered. Fourteen to 20 days (average of 17 days) later the NWQ-CS was re-administered. Test-retest reliability and validity of the NWQ-CS were assessed. RESULTS: Reliability and validity estimates did not differ with type of neighborhood. NWQ-CS measures of walking showed moderate to excellent reliability. Reliability was generally higher for estimates of weekly frequency than minutes of walking. Total weekly minutes of walking were moderately related to all accelerometry measures. Moderate-to-strong associations were found between the NWQ-CS and log-of-walks variables. The NWQ-CS yielded statistically significantly lower mean values of total walking, weekly minutes of walking for transportation and weekly frequency of walking for transportation outside the neighborhood than the log-of-walks. CONCLUSIONS: The NWQ-CS showed measurement invariance across types of neighborhoods. It is a valid measure of walking for recreation and frequency of walking for transport. However, it may systematically underestimate the duration of walking for transport in samples that engage in high levels of this type of walking. PMID- 22070769 TI - Acupuncture for depression: exploring model validity and the related issue of credibility in the context of designing a pragmatic trial. AB - INTRODUCTION: Evaluating care that is not credible to its practitioners or patients will result in a gap between evidence and practice and the potential value, or harm, of the intervention may be underestimated. Our aim was to develop a pragmatic trial that would have better model validity and credibility than trials to date in this clinical area. METHODS: In-depth interviews; a nominal consensus technique and five arm pilot trial conducted in UK primary care using counseling and usual general practitioner (GP) care as comparisons for acupuncture. FINDINGS: Patients with long standing, severe illness that had not responded, or partially responded to conventional treatments may be interested in using acupuncture and participating in a trial. Using a database method to recruit, pilot trial patients were mostly severely depressed (87.5%); chronically ill (60% with 3+ previous episodes), with high levels of comorbidity, and medication use. Acupuncture was as credible to pilot trial participants as usual GP care and more credible than counseling: most patients (62.5%) preferred to be allocated to acupuncture, rating it more highly at baseline than counseling or usual GP care as potentially able to benefit their depression (P = 0.002). Disparities were identified in the working models of acupuncturists and counselors that suggest inherent differences between interventions in terms of the process and intended potential outcomes of therapy, as well as the interaction between patients and therapists. CONCLUSION: The Medical Research Council (MRC) framework with its phased, mixed method approach has helped to develop research that has better model validity than trials to date in this field. The next phase of research will need to involve acupuncture and counseling practitioners to help researchers to develop realistic and credible care packages for a full-scale trial, where patients are likely to be severely and chronically ill. PMID- 22070770 TI - Noninvasive prenatal diagnosis of common fetal chromosomal aneuploidies by maternal plasma DNA sequencing. AB - OBJECTIVE: To develop a new bioinformatic method in the noninvasive prenatal identification of common fetal aneuploidies using massively parallel sequencing on maternal plasma. METHODS: Massively parallel sequencing was performed on plasma DNA samples from 108 pregnant women (median gestation: 12(+5) week) immediately before chorionic villus sampling (CVS) or amniocentesis. Data were analysed using a novel z-score method with internal reference chromosome. The diagnostic accuracies of the fetal karyotyping status were compared against two previously reported z-score methods--one without adjustment and the other with GC correction. RESULTS: A total of 32 cases with fetal aneuploidy were confirmed by conventional karyotyping, including 11 cases of Trisomy 21, 10 cases of Trisomy 18, 2 cases of Trisomy 13, 8 cases of Turner syndrome (45, XO) and one case of Klinefelter syndrome (47, XXY). Using the z-score method without reference adjustment, the detection rate for Trisomy 21, Trisomy 18, Trisomy 13, Turner syndrome, and Klinefelter's syndrome is 100%, 40%, 0%, 88% and 0% respectively. Using the z-score method with GC correction, the detection rate increased to 100% for Trisomy 21, 90% for Trisomy 18, 100% for Trisomy 13. By using the z-score method with internal reference, the detection rate increased to 100% for all aneuploidies. The false positive rate was 0% for all three methods. CONCLUSION: This massively parallel sequencing-based approach, combined with the improved z score test methodology, enables the prenatal diagnosis of most common aneuploidies with a high degree of accuracy, even in the first trimester of pregnancy. PMID- 22070771 TI - Evaluation of the training and support received by facilitators of a cancer education and support programme in New Zealand. AB - This study evaluates the training and support provided for facilitators who deliver the Living Well programme. This education and support programme, offered by the Cancer Society of New Zealand since 1991, aims to demystify cancer and its treatments, and develop self-efficacy of cancer patients and their supporters. A purposeful sample of 17 facilitators from five regions across New Zealand participated in semi-structured interviews. Quantitative data on demographics, qualifications and history with the programme were subjected to a frequency analysis. A thematic content analysis was conducted on qualitative data regarding the experiences of the facilitators with the training programme and the level and quality of subsequent support. Facilitators (aged 35-65, 16 of whom were women), came from a variety of socio-economic and educational backgrounds with a significant number having health-related roles and qualifications. Facilitator training was seen as relevant, thorough, effective and good preparation for the demands of the role. The pairing of more experienced staff and volunteers to co facilitate was a particularly successful aspect of the programme. The main drawbacks were limited access to support, lack of supervision and a perceived lack of appreciation from the organisation for the volunteer facilitators. PMID- 22070772 TI - B-cell depletion extends the survival of GTKO.hCD46Tg pig heart xenografts in baboons for up to 8 months. AB - Xenotransplantation of genetically modified pig organs offers great potential to address the shortage of human organs for allotransplantation. Rejection in Gal knockout (GTKO) pigs due to elicited non-Gal antibody response required further genetic modifications of donor pigs and better control of the B-cell response to xenoantigens. We report significant prolongation of heterotopic alpha Galactosyl transferase "knock-out" and human CD46 transgenic (GTKO.hCD46Tg) pig cardiac xenografts survival in specific pathogen free baboons. Peritransplant B-cell depletion using 4 weekly doses of anti-CD20 antibody in the context of an established ATG, anti-CD154 and MMF-based immunosuppressive regimen prolonged GTKO.hCD46Tg graft survival for up to 236 days (n = 9, median survival 71 days and mean survival 94 days). B-cell depletion persisted for over 2 months, and elicited anti-non-Gal antibody production remained suppressed for the duration of graft follow-up. This result identifies a critical role for B cells in the mechanisms of elicited anti-non-Gal antibody and delayed xenograft rejection. Model-related morbidity due to variety of causes was seen in these experiments, suggesting that further therapeutic interventions, including candidate genetic modifications of donor pigs, may be necessary to reduce late morbidity in this model to a clinically manageable level. PMID- 22070773 TI - Using timelines as part of recovery-focused practice in psychosis. AB - The value of timelines is discussed with regard to the promotion of recovery, particularly emphasizing relapse signature and concordance in medicine-taking. Recovery approaches in contemporary mental health care rely on understanding motivations, aspirations and decision making. In the authors' experience timelines are a useful way of working together with people to make sense of experiences, of which they may only have partial or intermittent awareness. The mental health workers' philosophical approach, the tools available to them and their skills and attributes, shape the therapeutic relationship. Timelines are a useful tool in helping reach the kind of joint understanding within a therapeutic relationship which characterizes concordance. As this relationship develops, decision making including that around medicine-taking and relapse signature, can be based on this shared understanding. Timeline examples (Tables 2 and 3) based on the fictitious experiences of Philip, a young man diagnosed with schizophrenia, show their application in recovery-focused practice. Further research is needed to enhance the limited evidence base underpinning timelines as a method of facilitating concordance. PMID- 22070774 TI - Detection of foot-and-mouth disease virus RNA by reverse transcription loop mediated isothermal amplification. AB - A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for foot-and-mouth disease virus (FMDV) RNA. The amplification was able to finish in 45 min under isothermal condition at 64 degrees C by employing a set of four primers targeting FMDV 2B. The assay showed higher sensitivity than RT-PCR. No cross reactivity was observed from other RNA viruses including classical swine fever virus, swine vesicular disease, porcine reproductive and respiratory syndrome virus, Japanese encephalitis virus. Furthermore, the assay correctly detected 84 FMDV positive samples but not 65 FMDV negative specimens. The result indicated the potential usefulness of the technique as a simple and rapid procedure for the detection of FMDV infection. PMID- 22070775 TI - Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain. AB - BACKGROUND: Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA) induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation. METHODS: Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG) neurons. RESULTS: In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA) at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation. CONCLUSIONS: In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression. PMID- 22070777 TI - Integrating fluctuating nitrate uptake and assimilation to robust homeostasis. AB - Nitrate is an important nitrogen source used by plants. Despite of the considerable variation in the amount of soil nitrate, plants keep cytosolic nitrate at a homeostatic controlled level. Here we describe a set of homeostatic controller motifs and their interaction that can maintain robust cytosolic nitrate homeostasis at fluctuating external nitrate concentrations and nitrate assimilation levels. The controller motifs are divided into two functional classes termed as inflow and outflow controllers. In the presence of high amounts of environmental nitrate, the function of outflow controllers is associated to efflux mechanisms removing excess of nitrate from the cytosol that is taken up by low-affinity transporter systems (LATS). Inflow controllers on the other hand maintain homeostasis in the presence of a high demand of nitrate by the cell relative to the amount of available environmental nitrate. This is achieved by either remobilizing nitrate from a vacuolar store, or by taking up nitrate by means of high-affinity transporter systems (HATS). By combining inflow and outflow controllers we demonstrate how nitrate uptake, assimilation, storage and efflux are integrated to a regulatory network that maintains cytosolic nitrate homeostasis at changing environmental conditions. PMID- 22070776 TI - Disruption of Trichoderma reesei cre2, encoding an ubiquitin C-terminal hydrolase, results in increased cellulase activity. AB - BACKGROUND: The filamentous fungus Trichoderma reesei (Hypocrea jecorina) is an important source of cellulases for use in the textile and alternative fuel industries. To fully understand the regulation of cellulase production in T. reesei, the role of a gene known to be involved in carbon regulation in Aspergillus nidulans, but unstudied in T. reesei, was investigated. RESULTS: The T. reesei orthologue of the A. nidulans creB gene, designated cre2, was identified and shown to be functional through heterologous complementation of a creB mutation in A. nidulans. A T. reesei strain was constructed using gene disruption techniques that contained a disrupted cre2 gene. This strain, JKTR2-6, exhibited phenotypes similar to the A. nidulans creB mutant strain both in carbon catabolite repressing, and in carbon catabolite derepressing conditions. Importantly, the disruption also led to elevated cellulase levels. CONCLUSIONS: These results demonstrate that cre2 is involved in cellulase expression. Since the disruption of cre2 increases the amount of cellulase activity, without severe morphological affects, targeting creB orthologues for disruption in other industrially useful filamentous fungi, such as Aspergillus oryzae, Trichoderma harzianum or Aspergillus niger may also lead to elevated hydrolytic enzyme activity in these species. PMID- 22070778 TI - Lethal osteogenesis imperfecta-like condition with cutis laxa and arterial tortuosity in MZ twins due to a homozygous fibulin-4 mutation. AB - This case report involved male infants of a size consistent with the estimated gestational age of 31 weeks. The mother of the twins was a 27-year-old, G4P3 woman with limited prenatal care who presented for cesarean delivery. Resuscitation efforts were initiated and continued until the infants became asystolic. Postmortem radiographs showed innumerable fractures of the limbs, ribs, and skull in various states of healing with callus formation; hence, the fractures were of prenatal origin. Despite the fractures, the growth of the long bones was not impaired. The radiographic findings were initially thought to represent osteogenesis imperfecta type IIC. However, there were also vascular anomalies not explained by this phenotype. Grossly, all arteries were elongated, thickened, and tortuous. The carotids, descending aorta, and iliac arteries were redundant to such an extent that they produced corkscrew patterns. There was also cutis laxa with loose, redundant skin over the entire body. Collagen genes did not show any mutations; however, when it was suggested Fibulin-4 be studied because of overlap with the condition described by Dasouki and colleagues in 2007, a homozygous premature stop codon mutation was found in that gene. PMID- 22070779 TI - Richard F. W. Bader: a true pioneer. PMID- 22070780 TI - Autobiography of Richard F. W. Bader. PMID- 22070783 TI - Miniaturized extinction culturing is the preferred strategy for rapid isolation of fast-growing methane-oxidizing bacteria. AB - Methane-oxidizing bacteria (MOB) have a large potential as a microbial sink for the greenhouse gas methane as well as for biotechnological purposes. However, their application in biotechnology has so far been hampered, in part due to the relative slow growth rate of the available strains. To enable the availability of novel strains, this study compares the isolation of MOB by conventional dilution plating with miniaturized extinction culturing, both performed after an initial enrichment step. The extinction approach rendered 22 MOB isolates from four environmental samples, while no MOB could be isolated by plating. In most cases, extinction culturing immediately yielded MOB monocultures making laborious purification redundant. Both type I (Methylomonas spp.) and type II (Methylosinus sp.) MOB were isolated. The isolated methanotrophic diversity represented at least 11 different strains and several novel species based on 16S rRNA gene sequence dissimilarity. These strains possessed the particulate (100%) and soluble (64%) methane monooxygenase gene. Also, 73% of the strains could be linked to a highly active fast-growing mixed MOB community. In conclusion, miniaturized extinction culturing was more efficient in rapidly isolating numerous MOB requiring little effort and fewer materials, compared with the more widely applied plating procedure. This miniaturized approach allowed straightforward isolation and could be very useful for subsequent screening of desired characteristics, in view of their future biotechnological potential. PMID- 22070784 TI - Comparison of salt stress resistance genes in transgenic Arabidopsis thaliana indicates that extent of transcriptomic change may not predict secondary phenotypic or fitness effects. AB - Engineered abiotic stress resistance is an important target for increasing agricultural productivity. There are concerns, however, regarding possible ecological impacts of transgenic crops. In contrast to the first wave of transgenic crops, many abiotic stress resistance genes can initiate complex downstream changes. Transcriptome profiling has been suggested as a comprehensive non-targeted approach to examine the secondary effects. We compared phenotypic and transcriptomic effects of constitutive expression of genes intended to confer salt stress tolerance by three different mechanisms: a transcription factor, CBF3/DREB1a; a metabolic gene, M6PR, for mannitol biosynthesis; and the Na+/H+ antiporter, SOS1. Transgenic CBF3, M6PR and SOS1 Arabidopsis thaliana were grown together in the growth chamber, greenhouse and field. In the absence of salt, M6PR and SOS1 lines performed comparably with wild type; CBF3 lines exhibited dwarfing as reported previously. All three transgenes conferred fitness advantage when subjected to 100 mm NaCl in the growth chamber. CBF3 and M6PR affected transcription of numerous abiotic stress-related genes as measured by Affymetrix microarray analysis. M6PR additionally modified expression of biotic stress and oxidative stress genes. Transcriptional effects of SOS1 in the absence of salt were smaller and primarily limited to redox-related genes. The extent of transcriptome change, however, did not correlate with the effects on growth and reproduction. Thus, the magnitude of global transcriptome differences may not predict phenotypic differences upon which environment and selection act to influence fitness. These observations have implications for interpretation of transcriptome analyses in the context of risk assessment and emphasize the importance of evaluation within a phenotypic context. PMID- 22070785 TI - Mental health problems and medically unexplained physical symptoms in adult survivors of childhood sexual abuse: an integrative literature review. AB - People sexually abused in childhood are at higher risk than non-abused people of medically unexplained symptoms such as irritable bowel syndrome or chronic pain, with mental ill health and high healthcare use. Friction and frustration, with high, unproductive healthcare costs, can often develop between these patients and health-care professionals such as general practitioners and nursing staff. The aim of this integrative literature review was to seek a sound evidence base from which to develop helpful interventions, improve relationships and identify gaps in knowledge. It found some theories about interconnections among childhood sexual abuse mental health and medically unexplained symptoms, such as 'somatization' or 'secondary gain', were used prejudicially, stigmatizing survivors. Conflicting theories make more difficult the search for effective interventions. Researchers rarely collaborated with sexual abuse specialists. Emphasis on identifying key risk factors, rather than providing support or alleviating distress, and lack of studies where survivors voiced their own experiences, meant very few targeted interventions for this group were proposed. Recommendations to enable effective interventions include making abuse survivors the prime study focus; qualitative research with survivors, to assist doctors and nursing staff with sensitive care; case histories using medical records; prospective studies with sexually abused children; support for the growing field of neurobiological research. PMID- 22070786 TI - Parameter estimation of multiple item response profile model. AB - Multiple item response profile (MIRP) models are models with crossed fixed and random effects. At least one between-person factor is crossed with at least one within-person factor, and the persons nested within the levels of the between person factor are crossed with the items within levels of the within-person factor. Maximum likelihood estimation (MLE) of models for binary data with crossed random effects is challenging. This is because the marginal likelihood does not have a closed form, so that MLE requires numerical or Monte Carlo integration. In addition, the multidimensional structure of MIRPs makes the estimation complex. In this paper, three different estimation methods to meet these challenges are described: the Laplace approximation to the integrand; hierarchical Bayesian analysis, a simulation-based method; and an alternating imputation posterior with adaptive quadrature as the approximation to the integral. In addition, this paper discusses the advantages and disadvantages of these three estimation methods for MIRPs. The three algorithms are compared in a real data application and a simulation study was also done to compare their behaviour. PMID- 22070788 TI - Thoraco-omphalopagus conjoined twins in Chamois-coloured domestic goat kids. AB - Conjoined twins have been observed in a wide range of mammalian and non-mammalian species; they are considered to be more common in bovine, less frequent in sheep and pig and extremely rare in horse and goat. A pair of female conjoined twins was delivered from a 2-year-old Chamois-coloured domestic goat. Post-mortem examination revealed two identical and symmetrical twins, fused from the manubrium sterni to the region just caudal to the umbilicus. The rib cages were conjoined in the ventral plane with a single set of pericardial, pleural and peritoneal cavities. Internal examination revealed the presence of a common diaphragm and a single enlarged liver. Within a single central pericardium, two malformed hearts were present. Reports on this type of congenital duplication in goats have not been found in the literature. Thoracopagus and thoraco omphalopagus are the most common types of conjoined twins in human beings and are associated with the highest mortality because of the frequent incidence of complex cardiac anatomy. PMID- 22070787 TI - Alcohol and risk of admission to hospital for unintentional cutting or piercing injuries at home: a population-based case-crossover study. AB - BACKGROUND: Cutting and piercing injuries are among the leading causes of unintentional injury morbidity in developed countries. In New Zealand, cutting and piercing are second only to falls as the most frequent cause of unintentional home injuries resulting in admissions to hospital among people aged 20 to 64 years. Alcohol intake is known to be associated with many other types of injury. We used a case-crossover study to investigate the role of acute alcohol use (i.e., drinking during the previous 6 h) in unintentional cutting or piercing injuries at home. METHODS: A population-based case-crossover study was conducted. We identified all people aged 20 to 64 years, resident in one of three regions of the country (Greater Auckland, Waikato and Otago), who were admitted to public hospital within 48 h of an unintentional non-occupational cutting or piercing injury sustained at home (theirs or another's) from August 2008 to December 2009. The main exposure of interest was use of alcohol in the 6-hour period before the injury occurred and the corresponding time intervals 24 h before, and 1 week before, the injury. Other information was collected on known and potential confounders. Information was obtained during face-to-face interviews with cases, and through review of their medical charts. RESULTS: Of the 356 participants, 71% were male, and a third sustained injuries from contact with glass. After adjustment for other paired exposures, the odds ratio for injury after consuming 1 to 3 standard drinks of alcohol during the 6-hour period before the injury (compared to the day before), compared to none, was 1.77 (95% confidence interval 0.84 to 3.74), and for four or more drinks was 8.68 (95% confidence interval 3.11 to 24.3). Smokers had higher alcohol-related risks than non-smokers. CONCLUSIONS: Alcohol consumption increases the odds of unintentional cutting or piercing injury occurring at home and this risk increases with higher levels of drinking. PMID- 22070789 TI - European veterinary dissertations. PMID- 22070790 TI - Effects of immediate or delayed addition of platelet additive solution on the in vitro quality of apheresis platelets. AB - BACKGROUND: There is little knowledge how different hold times of hyperconcentrated platelet (PLT) suspensions (HPSs) before the addition of platelet additive solution (PAS) might affect PLT quality. We compared the in vitro quality of single-donor PLT concentrates (SDPs) with immediate or delayed PAS addition and studied the quality of collected concurrent plasma (CP). STUDY DESIGN AND METHODS: We collected 6*10(11) PLTs in 175 of mL plasma and CP from 31 donors. The HPSs were split into two parts, with 162 mL of modified PAS III (PAS IIIM) added immediately (0hr-SDP) or 2 hours later (2hr-SDP). Final SDPs had a targeted concentration of 1.2*10(12) PLTs/L and a PAS proportion of 65%. On Days 1, 5, and 7 we determined glucose and lactate concentration, pH, P-selectin expression, hypotonic shock response (HSR), and extent of shape change (ESC). Clotting Factor V (FV) and VIII (FVIII) activities and D-dimer concentration were determined in CP and donor. RESULTS: Glucose utilization, lactate production, and pH were similar for both kinds of products. Low P-selectin expression indicated no relevant PLT activation during storage. HSR and ESC were similarly well preserved. Recoveries of FV and FVIII were 100.0+/-14.0 and 98.6+/-14.9%, respectively. Concentrations of D-dimers in the donor and CP were 173.7+/-90.1 and 177.6+/-91.2 ng/dL, respectively. CONCLUSIONS: Adding PAS immediately or 2 hours after collection does not result in different in vitro quality of PLTs stored up to 7 days. The good recovery of clotting factors with no signs of activation indicates a good quality of CP. PMID- 22070791 TI - Monitoring and documentation of side effects from depot antipsychotic medication: an interdisciplinary audit of practice in a regional mental health service. AB - This audit reviewed current practice within a rural mental health service area on the monitoring and documentation of side effects of antipsychotic depot medication. A sample of 60 case files, care plans and prescriptions were audited, which is 31% of the total number of service users receiving depot injections in the mental health service region (n= 181). The sample audited had a range of diagnoses, including: schizophrenia, schizoaffective disorder, bipolar affective disorder, depression, alcoholic hallucinosis and autism. The audit results revealed that most service users had an annual documented medical review and a documented prescription. However, only five (8%) case notes examined had documentation recorded describing the condition of the injection site, and alternation of the injection site was recorded in only 28 (47%) case notes. No case notes examined had written consent to commence treatment recorded. In 57 (95%) of case notes, no documentation of recorded information on the depot and on side effects was given. The failure to monitor and record some blood tests was partly attributed to a lack of clarity regarding whose responsibility it was. A standardized checklist has been developed as a result of the audit and this will be introduced by all teams across the service. PMID- 22070792 TI - Causes of primary amenorrhea: a report of 295 cases in Thailand. AB - AIMS: The aim of this study was to determine the prevalence of etiologic causes of primary amenorrhea in Thailand. METHODS: A retrospective study was performed using 295 complete medical records of women with primary amenorrhea who attended the Gynecologic Endocrinology Clinic, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand from September 1992 to February 2009. RESULTS: The three most common causes of primary amenorrhea were Mullerian agenesis (39.7%), gonadal dysgenesis (35.3%), and hypogonadotropic hypogonadism (9.2%). Amongst 88 cases of gonadal dysgenesis, 59 cases (67.0%) incurred abnormal karyotype including 45X (n=21), mosaic (n=31), and others (n=7). CONCLUSIONS: The present study has currently been the largest case series of primary amenorrhea. Mullerian agenesis is the most prevalent cause in our study, while gonadal dysgenesis is the most common cause in the largest scale study in the USA. Hence, racial, genetic and environmental factors could play roles in the cause of primary amenorrhea. PMID- 22070793 TI - Fetal and maternal heart rate confusion during intra-partum monitoring: comparison of trans-abdominal fetal electrocardiogram and Doppler telemetry. AB - OBJECTIVE: To compare intra-partum performance of trans-abdominal electrocardiogram with Doppler telemetry. METHODS: In this prospective longitudinal study, simultaneous monitoring with trans-abdominal ECG and Doppler telemetry was performed in 41 uncomplicated term singleton pregnancies during labour. RESULTS: The overall success rate for FHR monitoring was similar between trans-abdominal ECG and Doppler telemetry (88.5 +/- 16.7% vs 89.4 +/- 7.6%), except for the second stage of labour. A significantly higher rate of confusion (p < 0.001) between fetal and maternal heart was found for Doppler telemetry (4.5 +/- 4.5%) compared with trans-abdominal ECG (1.3 +/- 1.9%), especially in the second stage and during maternal movements. CONCLUSIONS: Trans-abdominal ECG monitoring is feasible, with comparable success rate to traditional Doppler telemetry, without interfering with maternal mobility or requiring midwife intervention. The reduction in maternal?fetal heart rate confusion from trans abdominal ECG could reduce incorrect obstetric interpretation. PMID- 22070794 TI - CA19-9-producing early gastric adenocarcinoma arising in hyperplastic foveolar polyp: a very unique resection case. AB - Here we report the first case of carbohydrate antigen (CA) 19-9-producing early gastric adenocarcinoma arising in polyp. A solitary pedunculated polyp lesion of the stomach, measuring 26 * 20 * 20 mm, was noticed in a 76-year-old Japanese woman due to an abdominal disorder, associated with a markedly high serum CA19-9 level (2,172.6 U/ml). After endoscopic mucosal resection was performed, the CA19 9 level was drastically decreased and normalized. The scanning view of immunohistochemical staining of CA19-9 exhibited a focal, not diffuse, positive expression in the hyperplastic epithelium and, especially, in the irregular and fused tubular glands and the mucinous material secreted into the dilated glands. In particular, microscopic examination of the strongly CA19-9-positive areas showed structurally atypical epithelium containing mildly to focal moderately enlarged nuclei and prominent nucleoli with loss of cellular polarity, estimated as adenocarcinoma. No stromal invasion was evident. Immunohistochemically, distinct nuclear stainings for p53 and Ki-67 were seen, occasionally conforming to the CA19-9-positive atypical cells, respectively, confirmed by double immunostaining. These hyperplastic and atypical cells were classified into the pure gastric phenotype by mucin histochemical methods. Based on these features, we finally made a conclusive diagnosis of CA19-9-producing in situ well differentiated adenocarcinoma of gastric type arising in hyperplastic foveolar polyp. We suggest that the markedly high serum CA 19-9 level could be indicative of carcinoma in polyp at the very least. PMID- 22070795 TI - 'It's easier just to separate them': practice constructions in the mental health care and support of younger people with dementia and their families. AB - There is no standard model of specialist care for younger people with dementia (onset before the age of 65 years) and specialist service provision varies widely throughout the UK. In order to gain a clearer picture about ways in which clinical staff work with younger people with dementia, semi-structured interviews were conducted with dementia care staff working in the north-west of England. Interviews focused on exploring daily working practices and the meaning placed on clinical decision making when involving family/carers in routine practice. Content analysis generated three core themes: (1) Maintaining Separation: how clinical staff conceptualize the meaning of 'family' in the provision of dementia care services; (2) Providing Practical Help: the focus in care provision on assisting families with aspects of daily life such as finances, education and physical care; and (3) Acknowledging the Family Context: how staff understand and interact with family members in an attempt to initiate care, utilizing biographically informed practice. By understanding how staff view their role in providing younger people with dementia with effective, high-quality dementia care, it is anticipated that a more family-centred approach can be integrated into already established patterns of working that more holistically meet the needs of this group. PMID- 22070796 TI - Clinical efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors, in patients with cognitive impairment: a comparative open study. AB - INTRODUCTION: Dementia constitutes an increasingly prevalent cognitive disorder with serious socioeconomic implications. AIMS: In the present study, we aimed to evaluate the efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors (ChEIs), in terms of several neuropsychological parameters, in a considerable number of patients with dementia. RESULTS: In our prospective, open-label study, we enrolled a total of 276 patients (mean age 71 +/- 8 years, 95 males) with cognitive disorders. Our study population comprised four groups: no treatment group (n = 75), aniracetam monotherapy group (n = 58), ChEIs monotherapy group (n = 68), and group of combined treatment (n = 68). Patients were examined with validated neuropsychological tests at baseline, 3, 6, and 12 months of treatment. In patients treated with aniracetam, all studied parameters were adequately maintained at 6 and 12 months, while emotional state was significantly improved at 3 months. In patients treated with ChEIs, we observed a significant cognitive deterioration at 12 months. The comparison between aniracetam and ChEIs in patients with relatively mild dementia (15 <= MMSE <= 25) revealed a significantly better cognitive performance with aniracetam at 6 months and improved functionality at 3 months. Comparing aniracetam monotherapy with combined treatment in the same population, aniracetam performed better in the cognitive scale at 6 months, and displayed a notable tendency for enhanced mood at 12 months and improved functionality at 6 months. CONCLUSIONS: Our findings indicate that aniracetam (a nootropic compound with glutamatergic activity and neuroprotective potential) is a promising option for patients with cognitive deficit of mild severity. It preserved all neuropsychological parameters for at least 12 months, and seemed to exert a favorable effect on emotional stability of demented patients. PMID- 22070797 TI - Working while receiving chemotherapy: a survey of patients' experiences and factors that influence these. AB - The purpose of this study was to estimate the number of patients who continue to work when undergoing ambulatory chemotherapy and to identify personal or treatment-related factors that influence this. Patients undergoing final cycles of adjuvant chemotherapy for breast or colorectal cancer or first-line chemotherapy for lymphoma at two cancer treatment centres were approached to take part in a cross sectional survey (n= 55, RR 55%). Sixty-four per cent (n= 35) of respondents were working when cancer was diagnosed. Fifty-four per cent (n= 19) of respondents were working when chemotherapy began but as treatment progressed only 29% (n= 10) continued to work in any capacity. The most important influencing factor when making decisions about work was the need to concentrate on looking after oneself. Overall, respondents found their employers and colleagues supportive but there was some evidence they became less supportive as treatment progressed. While this was a small study it highlights the need for health care professionals to understand patient's needs and wishes in relation to work while undergoing chemotherapy by including this issue as part of routine assessment. Strategies to allow those who wish to continue to work during treatment should be put in place early to support this. PMID- 22070798 TI - The quality of the working alliance between chronic psychiatric patients and their case managers: process and outcomes. AB - The concept of a working alliance is rooted in psychotherapy and has been studied extensively in that field. Much less research has been conducted into working alliances between chronic psychiatric patients and their case managers. The aim of this review was to identify what is known about the working alliance between chronic psychiatric patients and their case managers. An extensive survey of the literature produced 14 articles for this review. The results of studies conducted show that a good working alliance has positive effects on the functioning of patients, and that the quality of the alliance depends on both patient characteristics and the behaviour of the case managers. The results also indicate that the working alliance is largely determined in the first 3 months of the contact. Further research into the development of working alliances is necessary. PMID- 22070799 TI - Bystander activation of iNKT cells occurs during conventional T-cell alloresponses. AB - It is well established that iNKT cells can be activated by both exogenous and a limited number of endogenous glycolipids. However, although iNKT cells have been implicated in the immune response to transplanted organs, the mechanisms by which iNKT cells are activated in this context remain unknown. Here we demonstrate that iNKT cells are not activated by allogeneic cells per se, but expand, both in vitro and in vivo, in the presence of a concomitant conventional T-cell response to alloantigen. This form of iNKT activation was found to occur independently of TCR-glycolipid/CD1d interactions but rather was a result of sequestration of IL-2 produced by conventional alloreactive T cells. These results show for the first time that IL-2, produced by activated conventional T cells, can activate iNKT cells independently of glycolipid/CD1d recognition. Therefore, we propose that the well-documented involvement of iNKT cells in autoimmunity, the control of cancer as well as following transplantation need not involve recognition of endogenous or exogenous glycolipids but alternatively may be a consequence of specific adaptive immune responses. PMID- 22070800 TI - An examination of the health and wellbeing of childless women: a cross-sectional exploratory study in Victoria, Australia. AB - BACKGROUND: Childlessness among Australian women is increasing. Despite this, little is known about the physical and mental health and wellbeing of childless women, particularly during the reproductive years. The aims of this exploratory study were to: 1) describe the physical and mental health and wellbeing and lifestyle behaviours of childless women who are currently within the latter part of their reproductive years (30 - 45 years of age); and 2) compare the physical and mental health and wellbeing and lifestyle behaviours of these childless women to Australian population norms. METHODS: A convenience sample of 50 women aged between 30 and 45 years were recruited to participate in a computer assisted telephone interview. The SF-36 Health Survey v2 and lifestyle indicators were collected in regards to women's health and wellbeing. Data were analysed using descriptive statistics, t-tests for independent sample means and 95% confidence intervals for the difference between two independent proportions. RESULTS: Childless women in this study reported statistically significant poorer general health, vitality, social functioning and mental health when compared to the adult female population of Australia. With the exception of vegetable consumption, lifestyle behaviours were similar for the childless sample compared to the adult female population in Australia. CONCLUSIONS: Childless women may be at a greater risk of experiencing poor physical and mental health when compared to the Australian population. A woman's health and wellbeing during her reproductive years may have longer term health consequences and as such the health and wellbeing of childless women requires further investigation to identify and address implications for the provision of health (and other social) services for this growing population group. PMID- 22070801 TI - A histochemical comparison of methylene-blue/acid fuchsin with hematoxylin and eosin for differentiating calcification of stromal tissue. AB - Benign and malignant connective tissue tumors consist of a fibrous component that contains varying amounts of one or more types of bone or other calcified tissue. Diagnosis of these connective tissue tumors often poses challenges for pathologists, because it is difficult to differentiate the organic matrix of osteoid from hyalinized stroma. To establish a definitive diagnosis, it sometimes is advantageous to demonstrate histologically by special staining either the type of calcification or the presence or absence of calcification. We compared the efficacy of methylene blue-acid fuchsin (MB-AF) to hematoxylin and eosin (H-E) for connective tissue tumors suspected to contain calcifications and to devise an optimal staining technique for calcification that would be specific, simple, and cost- and time-effective. We examined 50 benign and 45 malignant connective tissue tumors that were suspected to contain calcifications. Sections were stained with H-E and MB-AF and evaluated. MB-AF stained bone pink, which contrasted with blue soft tissue. After MB-AF staining, osteoid was faint pink in a blue stromal background. Osteoid was not visualized in H-E stained sections; it was stained the same shade of pink as stromal tissue. Dystrophic calcification and cementum could be identified equally well using either staining technique, but contrast was better after H-E staining. MB-AF staining of bone was comparable to H-E staining and could be used effectively to stain bone and osteoid. MB-AF is a simple, single step procedure. It also stains cementum blue with faint blue rimming and dystrophic calcification bluish-pink, but it cannot be used as a specific stain for types of calcification other than bone and osteoid. PMID- 22070802 TI - Removal of prion infectivity by affinity ligand chromatography during OctaplasLG(r) manufacturing--results from animal bioassay studies. AB - BACKGROUND: OctaplasLG((r)) is a 2nd-generation virus inactivated pooled plasma for infusion. Prions are removed by the principle of chromatography, utilizing an affinity ligand gel (LG) developed for binding of prion proteins and their infectivity. The goal of this study was to verify, using the gold standard animal bioassay system, whether or not prion infectivity can be removed by the LG affinity step under conditions used in the routine manufacturing process. MATERIALS AND METHODS: Aliquots of pooled plasma were spiked with a microsomal/cytosolic (MIC) fraction of brain-derived hamster-adapted scrapie 263K and subjected to the OctaplasLG((r)) manufacturing process. Validated Western blot tests and animal bioassays studies were performed to determine the logarithmic reduction factors (RF) and the prion infectivity binding capacity. RESULTS: Bioassay studies demonstrated different logarithmic RFs (i.e. 1.73 and 0.76 log(10)) at two different plasma-to-resin ratios, the latter one representing the actual manufacturing ratio of 100:1, which can be explained by the differences in the study design. However, both bioassay studies showed a reproducible and high prion infectivity binding capacity of >=5.64 log(10) ID(50)/ml gel. CONCLUSION: Bioassay studies confirmed the capacity of the LG to bind brain-derived MIC prion proteins spiked into plasma. Even through infectivity was still detected following passage over the LG, this can be attributed to the high loads used in the study design, and the binding capacity of the LG still ensures a significant safety margin--binding the prion agents at the levels of prion infectivity that might be present in plasma and beyond. PMID- 22070803 TI - Influence of customized composite resin fibreglass posts on the mechanics of restored treated teeth. AB - AIM: To evaluate the mechanical behaviour of the dentine/cement/post interface of a maxillary central incisor using the finite element method and to compare the stresses exerted using conventional or customized post cementation techniques. METHODOLOGY: Four models of a maxillary central incisor were created using fibreglass posts cemented with several techniques: FGP1, a 1-mm-diameter conventionally cemented post; CFGP1, a 1-mm-diameter customized composite resin post; FGP2, a 2-mm-diameter conventionally cemented post; CFGP2, a 2-mm-diameter customized composite resin post. A distributed load of 1N was applied to the lingual aspect of the tooth at 45 degrees to its long axis. Additionally, polymerization shrinkage of 1% was simulated for the resin cement. The surface of the periodontal ligament was fixed in the three axes (X =Y = Z = 0). The maximum principal stress (sigma(max) ), minimum principal stress (sigma(min)), equivalent von Mises stress (sigma(vM) ) and shear stress (sigma(shear)) were calculated for the dentine/cement/post interface using finite element software. RESULTS: The peak of sigma(max) for the cement layer occurred first in CFGP1 (1.77 MPa), followed by CFGP2 (0.99), FGP2 (0.44) and FGP1 (0.2). The shrinkage stress (sigma(vM) ) of the cement layer occurred as follows: FGP1 (35 MPa), FGP2 (34), CFGP1 (30.7) and CFGP2 (30.1). CONCLUSIONS: Under incisal loading, the cement layer of customized posts had higher stress concentrations. The conventional posts showed higher stress because of polymerization shrinkage. PMID- 22070804 TI - Practical synthesis of 2-keto-3-deoxy-D-glycero-D-galactononulosonic acid (KDN). AB - Reaction of propargylmagnesium bromide with 2,3;5,6-di-O-isopropylidene-D mannonolactone followed by highly stereoselective reduction of the so-formed lactol with sodium borohydride gives a syn-diol from which practical syntheses of 2-keto-3-deoxy-D-glycero-D-galactononulosonic acid (KDN) and various partially protected derivatives have been achieved all of which feature the oxidative unmasking of the alpha-keto acid moiety from the alkyne. PMID- 22070806 TI - Systemic and central immunity in Alzheimer's disease: therapeutic implications. AB - Clinical pharmaceutical trials aimed at modulating the immune system in Alzheimer's Disease have largely focused on either dampening down central proinflammatory innate immunity or have manipulated adaptive immunity to facilitate the removal of centrally deposited beta amyloid. To date, these trials have had mixed clinical therapeutic effects. However, a number of clinical studies have demonstrated disturbances of both systemic and central innate immunity in Alzheimer's Disease and attention has been drawn to the close communication pathways between central and systemic immunity. This paper highlights the need to take into account the potential systemic effects of drugs aimed at modulating central immunity and the possibility of developing novel therapeutic approaches based on the manipulation of systemic immunity and its communication with the central nervous system. PMID- 22070824 TI - Immunoprecipitation of equine CD molecules using anti-human MABs previously analyzed by flow cytometry and immunohistochemistry. AB - Earlier studies investigating the cross-reactivity of antibodies submitted to the HLDA8 had used flow cytometry as a method of choice to screen mAbs for reactivity with equine leukocytes, including two-color flow-cytometry to characterize the lymphocyte population they detect. In addition, immuno-histochemistry (IHC) was used to detect distribution of positive cells in lymphoid tissue sections. In this study we performed immunoprecipitation (IP) to complement the previous results and add valuable information regarding the molecules detected by the cross-reacting antibodies. Surface molecules from primary equine PBMC or the equine cell line T8888 were biotinylated prior to precipitation to determine the molecular weight of the corresponding molecules in a western blot using streptavidin-AP. 21 out of 24 mAbs precipitated the molecules with a MW corresponding to its human orthologue. Positive mAbs were directed against CD2, CD5, CD11a, CD11b, CD14, CD18, CD21, CD44, CD83, CD91, CD172a, MHCI and MHCII. Three mAbs directed against CD49d, CD163, and CD206 which were unambiguously identified earlier by flow cytometry failed to immunoprecipitate the corresponding CD molecule. MAbs detecting CD molecules which are expressed internally like CD68 and mAbs of IgM class could not be included into this approach. PMID- 22070805 TI - Childhood internalizing behaviour: analysis and implications. AB - The concept of 'internalizing behaviour' reflects a child's emotional or psychological state and typically includes depressive disorders, anxiety disorders, somatic complaints and teenage suicide. Genetic and environmental causes have been largely implicated, although research continues to explore social etiological factors. Some research suggests females may be especially vulnerable to internalizing disorders, while data across ethnicities are somewhat variable. Regarding treatment, cognitive-behavioural therapies and use of pharmacological approaches (i.e. selective serotonin reuptake inhibitors) have both shown great promise in reducing symptoms of internalizing disorders. However, given the role of the social environment, prevention programmes aimed at reducing exposure to drugs, violence/abuse and environmental toxins are highly important. Internalizing disorders are associated with a host of deleterious outcomes (e.g. school drop-out, substance use and potentially suicide) as well as psychopathological outcomes (e.g. co-morbid anxiety or depression, externalizing disorders - including suicide). Children with mental health problems suffer educationally and are more likely to become entangled in the justice and welfare systems. Clearly, early treatment and prevention programmes for internalizing disorders need to be a priority from a public health perspective as well as from a family and community perspective. PMID- 22070825 TI - Somatic hypermutation leads to diversification of the heavy chain immunoglobulin repertoire in cattle. AB - The availability of unique variable (VH), diversity (D), and joining (JH) gene segments in the vertebrate germline determines the extent to which a primary immunoglobulin (Ig) repertoire can be generated through combinatorial rearrangement. Although bovine D segments possess unusual properties, the diversity of the primary Ig heavy chain (IgH) repertoire in cattle is restricted by the dominance of a single family of germline VH genes of limited number and diversity. Cattle therefore must employ other diversification strategies in order to generate a functional IgH repertoire, the main candidates being gene conversion and somatic hypermutation. In considering these possibilities, we predicted that if somatic hypermutation was active during B lymphocyte development, the process would introduce nucleotide substitutions to the VDJ exon and also non-coding region lying downstream of the rearranged JH segment. In contrast, our expectation was that gene conversion would show a greater tendency to confine modification to the IgH coding sequence, leaving intron regions substantially unmodified. An analysis of rearranged IgH sequences from cattle of different ages revealed that the diversification of germline sequences could be observed in very young calves and that substitution frequency increased with age. The age-dependent accumulation of mutations was particularly apparent in the second IgH complementarity-determining region (CDR2). Single base substitutions were found to predominate, with purines targeted more frequently than pyrimidines and transitions favoured over transversions. In non-coding regions, mutations were detected at a normalised frequency that was indistinguishable from that observed in CDR2. These data are consistent with a process of IgH diversification driven predominantly by somatic hypermutation. PMID- 22070826 TI - Differences in the peripheral immune response between lambs and adult ewes experimentally infected with Mycobacterium avium subspecies paratuberculosis. AB - The peripheral immune response, and its relationship with the outcome of the infection according to the age of the animal, has been investigated in young lambs and adult ewes experimentally infected with two different doses of Mycobacterium avium subspecies paratuberculosis (Map). Sixteen 1.5-month-old lambs out of 24 and 23 adult ewes out of 30 were orally challenged with an ovine Map field isolate. Animals were divided into two groups: HD, infected with a higher dose of Map and LD, with a lower dose. The remaining animals were used as uninfected control groups. Animals were euthanized at 110-120 and 210-220 days post-infection (dpi). Along the experiment, the humoral response and the specific and non-specific IFN-gamma production were assessed. An intradermal skin test (IDT), using avian PPD, was also performed at 90 and 195 dpi. Samples of intestine and related lymphoid tissue were taken for histological, bacteriological and PCR studies. The Ab and IFN-gamma production as well as the IDT response appeared earlier and with more intensity in the adult ewes compared to the lambs. The basal non-specific IFN-gamma levels increased only in the adult ewes from the HD group. Animals from the LD and HD groups were positive to PCR; however, lesions consistent with paratuberculosis were exclusively observed in the HD group, both in lambs and in adult sheep, but they only progressed to more advanced stages in the former. These results suggest that the peripheral immune response induced by Map infection in the adult ewes is more efficient to control the progression of the infection than in lambs. This could likely be due to the existence of previous contacts with Map or other mycobacteria in the adult sheep compared to the young lambs. PMID- 22070828 TI - T-wave alternans immediately after an acute myocardial infarction. PMID- 22070827 TI - Plasma ADAMTS13, von Willebrand factor (VWF) and VWF propeptide profiles in patients with DIC and related diseases. AB - ADAMTS13, endothelial von Willebrand factor (VWF) and related proteins are involved in the pathogenesis of some life threatening systemic thrombotic coagulopathies. Changes of plasma ADAMTS13 activity in thrombotic thrombocytopenic purpura (TTP) is well known but is also involved in septic disseminated intravascular coagulation (DIC). Here we investigated the ADAMTS13 activity, VWF and VWF propeptide (VWFpp) antigens in 69 patients with DIC, 143 with non-DIC, 21 with thrombotic thrombocytopenic purpura (TTP) and 23 with atypical hemolytic uremic syndrome (aHUS) for diagnosis of DIC. The plasma ADAMTS13 activity was significantly low in patients with DIC, and the plasma levels of VWF and VWFpp antigens, were the highest in these patients, but there were no significant differences in the plasma VWFpp levels between the patients with DIC and those with aHUS. The difference in the plasma ADAMTS13 activity, the VWF and VWFpp antigens between DIC and non-DIC cases was significant in those with infectious and malignant diseases, but the difference in the VWFpp/ VWF ratio were significant only in subjects with infectious diseases. As an indicator for prognosis, the plasma levels of VWFpp were significantly higher in non survivors than in survivors. Then, VWFpp/ VWF ratio and VWFpp/ADAMATS13 ratio will be potent informative indicators in DIC. These findings suggest that ADAMTS13/VWF profiles may have important roles in the pathogenesis of DIC, and that ADAMTS13 and VWFpp are useful indicators for the diagnosis and prognosis of DIC. PMID- 22070829 TI - Crosslinked cellulose developed by CuAAC, a route to new materials. AB - This work deals with a novel and simple approach of cellulose reticulation using the Huisgen 1,3-dipolar cycloaddition, also known as a 'click chemistry' reaction, catalysed by copper and developed by Sharpless. This reaction is carried out by the addition of a true alkyne and an azide to form a triazole ring connecting the two polysaccharide chains. The addition of two different functions will allow us to control the crosslinking reaction, to avoid intra-chain reactions and thus to promote the creation of an enhanced three-dimensional network. Azidodeoxycellulose was obtained with a DS of 1.5 from tosyl cellulose. The propargylation reaction in aqueous media leading to propargylcellulose with a DS of 1.3. CuAAC reaction was performed between azidodeoxycellulose and propargylcellulose in a DMSO/H(2)O system using CuSO(4), 5H(2)O/sodium ascorbate as catalytic system. The modified cellulose products were analysed by infrared, NMR and X-ray photoelectron spectroscopies and resulting material was analysed using scanning electron microscopy (SEM). PMID- 22070830 TI - Structures of building blocks in clusters of sweetpotato amylopectin. AB - phi,beta-Limit dextrins of domains and clusters of sweetpotato amylopectin were subjected to extensive hydrolysis by Bacillus amyloliquefaciens alpha-amylase to release building blocks and reveal the internal structures of clusters. The composition of building blocks was analyzed by size-fractionation, gel permeation chromatography, and high performance anion exchange chromatography. Different domains and clusters had structurally similar building blocks with around three chains per building block and internal chain length around 2.9. Singly branched and doubly branched building blocks were the largest and second largest groups in the clusters. Type A clusters had more large building blocks and contained 5-6 blocks per cluster with an inter-block chain length (IB-CL) of 7.0, whereas type B clusters had less large building blocks and contained 3-4 blocks per cluster with IB-CL 7.9. Models on how the building blocks could be organized into type A and type B clusters are discussed. PMID- 22070831 TI - Extraction of cellulose-synthesizing activity of Gluconacetobacter xylinus by alkylmaltoside. AB - This study reinvestigated the synthesis of cellulose in vitro with a well-known cellulose-producing bacterium, Gluconacetobacter xylinus. Alkylmaltoside detergents, which are more frequently used in recent structural biological researches, are uniquely used in this study to solubilize cellulose-synthesizing activity from the cell membrane of G. xylinus. Activity comparable to that previously reported is obtained, while the synthesized cellulose is crystallized into a non-native polymorph of cellulose (cellulose II) as well as the previous studies. In spite of this failure to recover the native activity to synthesize cellulose I microfibril in vitro, the product is a polymer with a degree of polymerization greater than 45 as determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). It was thus concluded that the established protocol can solubilize cellulose-synthesizing activity of G. xylinus with polymerizing activity. PMID- 22070832 TI - Photochemical conversion of the o-nitrobenzyl-C-glucoside to a sugar lactone. AB - A new family of activated glycosidic compounds has been designed and synthesized: (2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-2-nitrophenylmethane (1). It is stable in conditions commonly used for synthesis, and it can be converted to a sugar lactone derivative merely by photoirradiation (lambda=365 nm): 2,3,4,6 tetra-O-acetyl-D-glucono-1,5-lactone (2). A mechanism for the reaction is proposed. The photochemical conversion of 1 in the presence of methanol has also been demonstrated, giving rise to methyl 2,3,4,6-tetra-O-acetyl-D-gluconate (3). PMID- 22070833 TI - Reconstruction of defects of maxillary sinus wall after removal of a huge odontogenic lesion using prebended 3D titanium-mesh and CAD/CAM technique. AB - A 63 year-old male with a huge odontogenic lesion of sinus maxillaris was treated with computer-assisted surgery. After resection of the odontogenic lesion, the sinus wall was reconstructed with a prebended 3D titanium-mesh using CAD/CAM technique. This work provides a new treatment device for maxillary reconstruction via rapid prototyping procedures. PMID- 22070834 TI - 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. PMID- 22070836 TI - 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. PMID- 22070838 TI - Preface. PMID- 22070839 TI - Load redistribution after desmotomy of the accessory ligament of the deep digital flexor tendon in adult horses. AB - Summary An analysis of joint moments was used to study the biomechanical implications, load redistribution and kinematic pattern following desmotomy of the accessory ligament of the deep digital flexor tendon (AL) in adult horses. Recordings of 6 sound horses were made before and 10 days after desmotomy of the AL of the right forelimb at the walk and the trot. Kinematic recordings of the right forelimb and the left distal forelimb were made using the CODA-3 system. Kinetic recordings of the ground reaction forces in both forelimbs were made using a Kistler force plate simultaneously with the kinematic recordings. Radiographic localisation of the CODA-3 markers in both distal limbs allowed an analysis of coffin and fetlock joint moments, moment arms and forces in the digital flexor tendons. No transfer of load from the operated to the contralateral limb was found. In the operated limb the total joint moment of the coffin joint decreased substantially due to a reduced moment arm of the vertical ground reaction force component during the entire stance phase, while the fetlock joint moment decreased only slightly. To compensate for the loss of AL function, the superficial digital flexor tendon (SDFT) took a higher load during midstance, while at the end of the stance phase, the deep digital flexor tendon (DDFT) carried a higher load with a marked load peak just before heel off. While the compensation was adequate during midstance (no changes in maximal hyperextension of the fetlock joint), a prolonged hyperextension of the fetlock joint together with a rapid flexion at the start of the swing phase indicated that the DDFT was unable to compensate completely for the loss of AL function. It was concluded that the changes in total joint moments and increases in loading of the SDFT and DDFT allow locomotion without serious overloading of the compensating tendons following AL desmotomy. PMID- 22070840 TI - Biomechanical effects of rocker-toed shoes in sound horses. AB - Summary In many Western European countries rocker-toed shoes are applied routinely in sound horses. This is in contrast to most Anglo-Saxon countries where rocker-toed shoes are used almost exclusively for corrective or orthopaedic shoeing. The purposes of rocker-toed shoes are to hasten or facilitate breakover, or to encourage breakover to occur at the centre of the toe. This study compares the biomechanical effects of rocker-toed shoes with standard flat shoes in twelve sound Dutch warmblood horses, using a modified CODA-3 gait analysis system and a force plate. The variables analysed were speed of breakover, the moment of force in the coffin joint which is related to the 'ease' of breakover, the flight arc of the hoof in the sagittal and horizontal planes and some more general linear, temporal and angular stride characteristics. No differences between rocker-toed shoes and standard flat shoes were found with respect to the duration or ease of breakover or the proximity of breakover to the centre of the toe. It is concluded that rocker-toed shoes do not influence the stride characteristics of sound Dutch warmblood horses, and the findings of this study showed no objective grounds for the use of rocker-toed shoes in sound horses. This study was financially supported by Interpolis Paardenverzekeringen. PMID- 22070841 TI - Are kinematics of the walk related to the locomotion of a warmblood horse at the trot? AB - Summary In purchase examinations or at studbook selection sales the locomotor apparatus of horses is judged both at walk and trot. To evaluate whether kinematics of the walk are related to the locomotion at the trot, fore and hind limb movements of a group of 24 26-month-old warmbloods were recorded at walk and trot on a treadmill (1.6 and 4 m/s) using a modified CODA-3 gait analysis system. The intralimb coordination patterns at walk and trot were compared, and temporal and spatial variables of these gaits were related. Stride and stance durations (s) were shorter at the trot, while the stance distance (m) and swing duration (s) remained the same. Moreover, the pattern of the joint angle-time curves at walk and trot looked rather similar, though shifted to the left at trot because of the shorter relative stance duration. During the stance phase, the shoulder, stifle and tarsal joints were more flexed throughout, while the carpal and fetlock joints were more maximally extended in the trot than in the walk. In the swing phase, the elbow, carpal, stifle, and tarsal joints were more flexed because of the higher 'operating' speed at the trot compared to the walk. All other kinematic variables at the trot could be predicted from the mean +/- 1sd of the values recorded at the walk. Moreover, nearly all kinematic variables at the walk correlated well with those at the trot, while variables indicating gait quality of the walk were similar to the ones identified previously for the trot. In conclusion, kinematics recorded at the walk in a group of horses were similar to and thus predictive for locomotion at the trot providing the decreased stance duration and the increased speed of the trot are taken into consideration. PMID- 22070842 TI - Thrombosis of the aorta and the caudal arteries in the horse; Additional diagnostics and a new surgical treatment. AB - Summary The prognosis of aortic-iliac thrombosis (TAI) is usually considered to be poor, although affected horses are reported to have recovered following treatment with sodium gluconate. This paper presents some diagnostic techniques to monitor the development of hypoxemia in the diseased limb and to visualise the extension of the thrombosis into the femoral artery. Also, a surgical technique using a Fogarty(r) thrombectomy catheter for partial or total removal of thrombi to restore blood flow, is described. One horse recovered completely, allowing it to resume its former career, the other horse improved. The preliminary results of surgical interference in horses with TAI are promising. PMID- 22070843 TI - Computed tomography and treatment of chronic temporomandibular joint arthritis in a sheep. AB - Summary Diagnostic imaging and treatment of destructive right temporomandibular joint (TMJ) arthritis in a sheep are discussed. Computed tomography (CT) appears to be an attractive technique for imaging TMJ lesions in sheep. Surgical curettage of a deformed TMJ can result in functional recovery. PMID- 22070844 TI - The diagnostic nerve block of the sesamoidean nerve: Desensitized structures and possible clinical applications. AB - Summary The sesamoidean nerve branches from the palmar nerve and runs towards the proximal sesamoid bone. To study the structures innervated by this nerve, a technique for blocking it was developed. The effect of this nerve block was determined in ponies with an induced lameness located in the lateral proximal sesamoid bone (5 ponies) or in the distal part of the lateral branch of the suspensory ligament (5 ponies), and in 10 horses with clinical sesamoidosis. A lameness provoked by the implantation of an expansion plug in the proximal sesamoid bone could, to a large extent, be anaesthetized by a sesamoidean nerve block. However, lameness due to a local tendonitis in the lateral branch of the suspensory ligament, was only partially eliminated by a sesamoidean nerve block. In horses with sesamoidosis the lameness improved, on average, by about 30%. It is concluded that the sesamoidean nerve contains sensory fibres that innervate the proximal sesamoid bone. The sesamoidean nerve block is highly specific for pain originating from the proximal sesamoid bone including the adjacent distal part of the extensor branch of the suspensory ligament. In horses suffering from sesamoidosis the main source of pain appears not to be located in the proximal sesamoid bone. The specificity of the sesamoidean nerve block makes it a useful technique for differentiating the site of a lameness located in the fetlock area. In full compliance with the Act on Animal Experiments, this study was evaluated and approved by the Ethical Committee of the Utrecht Veterinary Faculty. PMID- 22070845 TI - The effect of the high palmar nerve block and the ulnar nerve block on lameness provoked by a collagenase-induced tendonitis of the lateral branch of the suspensory ligament. AB - Summary Controversy exists with respect to the innervation of the suspensory ligament (SL) in the fore limb of the horse. It is uncertain whether this structure is exclusively innervated by branches of the ulnar nerve or also to some extent by median nerve branches. Ground Reaction Forces (GRF) were determined in horses before and after the induction of a tendonitis in the lateral branch of the SL by the injection of collagenase, and before and after a high palmar and an ulnar block respectively. The high palmar block succeeded in bringing all GRF variables back to their original values which the ulnar block did not. It is concluded that the SL is innervated by branches of both the ulnar and the median nerves, with the median nerve being relatively more important for the distal part of the SL. PMID- 22070846 TI - The effect of diagnostic regional nerve blocks in the fore limb on the locomotion of clinically sound horses. AB - Summary The practice of applying diagnostic nerve blocks relies on the assumption that the blocks in themselves do not alter the horse' s gait. This assumption has recently been challenged. In the present paper a series of sequential nerve blocks (low palmar digital block, abaxial sesamoid block, high palmar block) was applied to clinically sound horses. Before and after each block the gait was clinically scored and Ground Reaction Forces (GRF) were measured. Clinical scoring did not change after any of the nerve blocks. None of the GRF variables changed significantly except for a slight alteration of the time at which the longitudinal GRF changed from a decelerative to a propulsive force. It is concluded that the basic assumption that diagnostic nerve blocks do not essentially alter the gait of a sound horse is correct. PMID- 22070847 TI - Bioavailability of pivampicillin and ampicillin trihydrate administered as an oral paste in horses. AB - Summary Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses. Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only: The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg. Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 24 hours after administration. After administration of pivampicillin to starved and fed horses the mean areas under the plasma concentration-time curve (AUCs) were 23.0 and 19.3 MUg.h.ml(-1), respectively. After administration of ampicillintrihydrate to fed horses the mean AUC was 0.7 MUg.h.ml(-1). The peak plasma concentrations were 4.8, 6.7, and 0.1 MUg/ml, after administration of pivampicillin to starved and fed horses and of ampicillin trihydrate to fed horses, respectively. There was no statistically significant difference in peak plasma concentration or AUC between pivampicillin administered to starved or fed horses. It is concluded that pivampicillin administered as an oral paste at a dose of 19.9 mg/kg gives satisfactory plasma concentrations in both starved and fed horses, whereas ampicillin trihydrate produces negligible plasma concentrations. Pivampicillin binds to feedstuffs at the pH found in the horse's stomach and small intestine. After incubation for 6h at pH 6, approximately 15% remains in solution, and after incubation for 3h at pH 1.9, approximately 40% remains in solution. Ampicillin, which binds to feedstuffs to a lesser extent, has a lower bioavailability than pivampicillin. Therefore, binding to feedstuffs does not seem to be a critical factor in the absorption of aminopenicillins. PMID- 22070849 TI - Factors affecting assessment of severity of aggressive incidents: using the Staff Observation Aggression Scale - Revised (SOAS-R) in Japan. AB - The aim of this study is to investigate factors associated with overall judgements of aggression severity as provided by ward nurses, using the Japanese language version of the Staff Observation Aggression Scale - Revised (SOAS-R). Nurses who observed 326 aggressive incidents involving psychiatric inpatients at five mental health facilities in Japan provided their assessments of the incident severity both on the established rating scale, the SOAS-R, and on a visual analogue scale (VAS), a one-item scale to indicate overall aggression severity. To evaluate the factors influencing the VAS severity scores, a multiple regression analysis was performed, in which consumer, nurse and ward characteristics were added consecutively, along with SOAS-R severity scores as independent variables. SOAS-R scores explained 17.6% of the VAS severity scores. Independently from the SOAS-R scores, the gender and age of the aggressive consumers (adjusted R(2) = 10.0%), as well as the gender of the nurses who reported the aggression (adjusted R(2) = 4.1%), each explained VAS severity score to a significant degree. Apart from the SOAS-R scores, consumer and nurse characteristics appeared to influence the overall judgements of severity of aggressive incidents, which may be connected to decisions about the use of coercive measures, such as seclusion/restraint or forced medication. PMID- 22070850 TI - Antioxidant, anti-inflammatory and cytotoxicity of Phaleria macrocarpa (Boerl.) Scheff Fruit. AB - BACKGROUND: Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) originates from Papua Island, Indonesia and grows in tropical areas. The different parts of the fruit of P. macrocarpa were evaluated for antioxidant, anti-inflammatory, and cytotoxic activities. METHODS: Phaleria macrocarpa fruit were divided into pericarp, mesocarp and seed. All parts of the fruit were reflux extracted with methanol. The antioxidant activity of the extracts were characterized in various in vitro model systems such as FTC, TBA, DPPH radical, reducing power and NO radical. Anti-inflammatory assays were done by using NO production by macrophage RAW 264.7 cell lines induced by LPS/IFN-gamma and cytotoxic activities were determined by using several cancer cell lines and one normal cell line RESULTS: The results showed that different parts (pericarp, mesocarp, and seed) of Phaleria macrocarpa fruit contain various amount of total phenolic (59.2 +/- 0.04, 60.5 +/- 0.17, 47.7 +/- 1.04 mg gallic acid equivalent/g DW) and flavonoid compounds (161.3 +/- 1.58, 131.7 +/- 1.66, 35.9 +/- 2.47 mg rutin equivalent/g DW). Pericarp and mesocarp showed high antioxidant activities by using DPPH (71.97%, 62.41%), ferric reducing antioxidant power (92.35%, 78.78%) and NO scavenging activity (65.68%, 53.45%). Ferric thiocyanate and thiobarbituric acid tests showed appreciable antioxidant activity in the percentage hydroperoxides inhibitory activity from pericarp and mesocarp in the last day of the assay. Similarly, the pericarp and mesocarp inhibited inducible nitric oxide synthesis with values of 63.4 +/- 1.4% and 69.5 +/- 1.4% in macrophage RAW 264.7 cell lines induced by LPS/IFN-gamma indicating their notable anti-inflammatory potential. Cytotoxic activities against HT-29, MCF-7, HeLa and Chang cell lines were observed in all parts. CONCLUSIONS: These results indicated the possible application of P. macrocarpa fruit as a source of bioactive compounds, potent as an antioxidant, anti inflammatory and cytotoxic agents. PMID- 22070851 TI - Fibroblast growth factor 23 and the bone-vascular axis: lessons learned from animal studies. AB - Calcification of arteries and cardiac valves is observed commonly in dialysis patients and represents a major determinant of the heightened cardiovascular risk observed during chronic kidney disease (CKD) progression. Recent advances from clinical and basic science studies suggest that vascular calcification should be considered a systemic disease in which pathologic processes occurring in the bone and kidney contribute to calcium deposition in the vasculature. Among the factors potentially involved in the vascular-bone axis dysregulation associated with CKD, there now is increasing interest in the role of the phosphaturic hormone fibroblast growth factor 23 (FGF-23). Increased FGF-23 plasma levels are observed with a decrease in kidney function and predict the risk of future cardiovascular mortality. However, clinical data are still unclear about whether a direct pathogenetic effect of FGF-23 on vascular/kidney/bone health exists. In the last few years, a series of basic science studies, performed using engineered mice, have contributed important pathophysiologic information about FGF-23 activities. This review summarizes findings from these studies and discusses the potential role of FGF-23 during the pathologic interplay between kidney, vessels, and bone in CKD. PMID- 22070852 TI - Parental influence on adolescent smoking cessation: is there a gender difference? AB - We examined the association of parental disapproval of adolescent smoking and parental smoking status, with past smoking quit behaviors among daily-smoking, high school-aged adolescents, and also tested whether these associations differ for boys and girls. Adolescent regular smokers (N=253) completed questions on smoking behaviors, past smoking cessation behaviors, parental disapproval of smoking, and parental smoking. Past smoking cessation behaviors were defined as "the number of quit attempts that lasted longer than 24 hours" and "the longest number of days of abstinence". Logistic regression analyses showed that for all adolescents, even having one smoking parent was associated with decreased odds of being abstinent for longer than 2 days. However, for girls, not having any smoking parents was associated with greater duration of abstinence (>2 weeks). Having both parents, compared with not having any parents disapprove of smoking, was associated with greater number of quit attempts in boys, but this effect was not found in girls. The results indicate that parents have a salient role in adolescent smoking cessation behaviors, and this association appears to be gender specific. However, further research is needed to understand the mechanisms that explain gender differences in parental influence on adolescent smoking cessation behaviors. PMID- 22070853 TI - Single stage and multistage classification models for the prediction of liver fibrosis degree in patients with chronic hepatitis C infection. AB - Predicting significant fibrosis or cirrhosis in patients with hepatitis C virus has persistently preoccupied the research agenda of many specialized research centers. Many studies have been conducted to evaluate the use of readily available laboratory tests to predict significant fibrosis or cirrhosis with the purpose to substantially reduce the number of biopsies performed. Although many of them reported significant predictive values of several serum markers for the diagnosis of cirrhosis, none of these diagnostic techniques was successful in accurately predicting early stages of liver fibrosis. Therefore, in this study a single stage classification model and a multistage stepwise classification model based on Neural Network, Decision Tree, Logistic Regression, and Nearest Neighborhood clustering, have been developed to predict individual's liver fibrosis degree. Results showed that the area under the receiver operator curve (AUROC) values of the multistage model ranged from 0.874 to 0.974 which is a higher range than what is reported in current researches with similar conditions. PMID- 22070854 TI - Risk factors associated with altered fetal growth in patients with pregestational diabetes mellitus. AB - OBJECTIVE: To assess the risk factors for abnormal fetal growth in patients with pregestational diabetic mellitus (DM). METHODS: A retrospective study was performed in 336 patients with pregestational DM. Small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants were defined as newborns with birth weights < 10th percentile and > 90th percentile, respectively. Logistic regression analysis was performed to identify risk factors for SGA and LGA. RESULTS: Multivariate analysis of the patients with pregestational DM revealed a significant difference between patients who delivered SGA and appropriate-for gestational-age (AGA) infants in terms of retinopathy (OR = 5.73, 95%CI = 1.39 23.59) and hemoglobin A1C (HbA1C) before delivery (OR = 0.80, 95%CI = 0.68 - 0.94, with a 0.1% increase in DCCT unit). Multivariate analysis revealed a significant difference between patients who delivered LGA and AGA infants in terms of primipara (OR = 3.40, 95%CI = 1.47-7.87) and HbA1C before delivery (OR = 1.14, 95%CI = 1.07-1.21, with a 0.1% increase in DCCT unit). CONCLUSIONS: HbA1C before delivery influenced both SGA and LGA infants in patients with pregestational DM. Tight glycemic control might be harmful to fetal growth in pregestational diabetic patients, especially when complicated with retinopathy. PMID- 22070855 TI - Magnetic resonance imaging to guide surgical practice. PMID- 22070856 TI - Feasibility of non-contrast-enhanced magnetic resonance angiography for imaging upper extremity vasculature prior to vascular access creation. AB - OBJECTIVES: Preoperative mapping of arterial and venous anatomy helps to prevent postoperative complications after vascular access creation. The use of gadolinium in contrast-enhanced (CE) magnetic resonance angiography (MRA) has been linked to nephrogenic systemic fibrosis in patients with end-stage renal disease (ESRD). The purpose of this study was to evaluate non-contrast-enhanced (NCE) MRA for assessment of upper extremity and central vasculature and to compare it with CE MRA. METHODS: NCE and CE-MRA images were acquired in 10 healthy volunteers and 15 patients with ESRD. In each data set, two observers analysed 11 arterial and 16 venous segments with regard to image quality (0-4), presence of artefacts (0-2) and vessel-to-background ratio. RESULTS: More arterial segments were depicted using CE-MRA compared to NCE-MRA (99% vs. 96%, p = 0.001) with mean image quality of 3.80 vs. 2.68, (p < 0.001) and mean vessel-to-background ratio of 6.47 vs. 4.14 (p < 0.001). Ninety-one percent of the venous segments were portrayed using NCE-MRA vs. 80% using CE-MRA (p < 0.001). Mean image quality and vessel-to background ratio were 2.41 vs. 2.21 (p = 0.140) and 5.13 vs. 3.88 (p < 0.001), respectively. CONCLUSIONS: Although arterial image quality and vessel-to background ratios were lower, NCE-MRA is considered a feasible alternative to CE MRA in patients with ESRD who need imaging of the upper extremity and central vasculature prior to dialysis access creation. PMID- 22070857 TI - Synthesis of a new class of beta-iodo N-alkenyl 2-pyridones. AB - A new method for the synthesis of beta-iodo N-alkenyl 2-pyridones from substituted 2-propargyloxypyridines has been discovered . These compounds present a unique complement of orthogonal functionality and structural characteristics that are unavailable via other routes. The ready access to these compounds renders them an important entry point for the preparation of more complex N-alkyl pyridone-containing targets. PMID- 22070858 TI - Activity of oritavancin and comparators in vitro against standard and high inocula of Staphylococcus aureus. AB - In this study, the impact of inoculum density on the growth inhibitory and killing activities of oritavancin and comparators (vancomycin, daptomycin and linezolid) in vitro against four Staphylococcus aureus strains at clinically relevant drug concentrations was studied. Broth microdilution and time-kill assays were performed using a standard inoculum [ca. 10(5)colony-forming units (CFU)/mL as per Clinical and Laboratory Standards Institute (CLSI) guidelines] and a high inoculum (ca. 10(7)CFU/mL). Whereas minimal inhibitory concentrations (MICs) of comparators were 2-8-fold higher when tested at high inoculum, oritavancin MICs were 16-fold higher for all strains at the high inoculum relative to the standard inoculum. However, in time-kill assays, when tested at its fC(min) [trough concentration of free (non-protein-bound) drug] and fC(max) (peak concentration of non-protein-bound drug), oritavancin retained its bactericidal activity against a vancomycin-susceptible, meticillin-susceptible S. aureus (VS-MSSA) strain and a vancomycin-susceptible, meticillin-resistant S. aureus (VS-MRSA) strain both at standard and high inocula. At its fC(max), oritavancin was bactericidal at standard inoculum but not at high inoculum against two vancomycin-intermediate S. aureus (VISA) strains. Against both VISA strains at standard inoculum, oritavancin at its fC(min) reduced cell density by between 2 and 3 log (bacteriostatic), predicting that it will retain activity against certain VISA infections. However, oritavancin had no substantial growth inhibitory effect against either VISA strain at high inoculum, suggesting that in rare VISA infections with an anticipated high bacterial burden such as endocarditis, alternative oritavancin dosing strategies, including combinations with other agents, may be explored. PMID- 22070859 TI - Investigation of the effect of power ultrasound on the nucleation of water during freezing of agar gel samples in tubing vials. AB - Nucleation, as an important stage of freezing process, can be induced by the irradiation of power ultrasound. In this study, the effect of irradiation temperature (-2 degrees C, -3 degrees C, -4 degrees C and -5 degrees C), irradiation duration (0s, 1s, 3s, 5s, 10s or 15s) and ultrasound intensity (0.07 W cm(-2), 0.14 W cm(-2), 0.25 W cm(-2), 0.35 W cm(-2) and 0.42 W cm(-2)) on the dynamic nucleation of ice in agar gel samples was studied. The samples were frozen in an ethylene glycol-water mixture (-20 degrees C) in an ultrasonic bath system after putting them into tubing vials. Results indicated that ultrasound irradiation is able to initiate nucleation at different supercooled temperatures (from -5 degrees C to -2 degrees C) in agar gel if optimum intensity and duration of ultrasound were chosen. Evaluation of the effect of 0.25 W cm(-2) ultrasound intensity and different durations of ultrasound application on agar gels showed that 1s was not long enough to induce nucleation, 3s induced the nucleation repeatedly but longer irradiation durations resulted in the generation of heat and therefore nucleation was postponed. Investigation of the effect of ultrasound intensity revealed that higher intensities of ultrasound were effective when a shorter period of irradiation was used, while lower intensities only resulted in nucleation when a longer irradiation time was applied. In addition to this, higher intensities were not effective at longer irradiation times due to the heat generated in the samples by the heating effect of ultrasound. In conclusion, the use of ultrasound as a means to control the crystallization process offers promising application in freezing of solid foods, however, optimum conditions should be selected. PMID- 22070860 TI - Ultrasound and ionic liquid: an efficient combination to tune the mechanism of alkenes epoxidation. AB - In this proof of concept study, the advantageous properties of both H(2)O(2)/NaHCO(3)/imidazole/Mn(TPP)OAc oxidation system and MOPyrroNTf(2) ionic liquid have been combined under ultrasonic irradiation to give an exceptionally favorable environment for Mn(TPP)OAc catalyzed olefin oxidations. The results reveal the crucial role played by the ultrasonic irradiations that influence drastically the oxidation process. In MOPyrroNTf(2) and under ultrasonic irradiation, the mechanism probably involves an oxo-manganyl intermediate at the expense of the classical bicarbonate-activated peroxide route. PMID- 22070861 TI - Prevalence and predictors of exclusive breastfeeding among women in Kigoma region, Western Tanzania: a community based cross-sectional study. AB - BACKGROUND: Exclusive breastfeeding (EBF) for the first six months of infants' lives is a cost effective intervention in saving children's lives and can avert 13 - 15% of the 9 million deaths of children under 5 years old in resource poor settings. However, EBF rates have been shown to be low in resource poor settings, ranging between 20 and 40%. In Tanzania, the prevalence of EBF among infants under 6 months is 41%, with limited information on predictors of EBF. The aim of the study was to determine prevalence of EBF and its predictors in Kigoma Municipality, Western Tanzania. METHODS: A cross-sectional study was conducted in March to May 2010 among 402 consenting women, with infants aged 6 to 12 months, from randomly selected households. A questionnaire was used to collect information on demographic characteristics, knowledge of EBF, infant feeding practices, and on HIV status. RESULTS: The prevalence of EBF among women in Kigoma Municipality was 58%. Knowledge of EBF was relatively higher (86%) compared to the practice. In the multivariable analysis, women with adequate knowledge of EBF (AOR 5.4), women who delivered at health facilities (AOR 3.0) and women who had no problems related to breasts, like engorgement/cracked nipples (AOR 6.6) were more likely to exclusively breastfeed compared to others. CONCLUSIONS: Prevalence of EBF in Kigoma municipality was slightly higher than the national figure of 41%, however it was way below the EBF prevalence of 90% recommended by the WHO. Strategies that target improving knowledge and skills for lactation management among women, as well as strategies to improve health facility delivery, may help to improve EBF in this setting. PMID- 22070862 TI - The process of change in psychotherapy for depression: helping clients to reformulate the problem. AB - There is increasing interest in mental health nurses delivering structured short term evidence-based psychotherapies such as cognitive behavioural therapy (CBT) and interpersonal psychotherapy (IPT); however, while there is evidence of the efficacy of psychotherapy for depression, there is limited understanding of the treatment processes. Data were drawn from audio tapes of CBT and IPT sessions for treatment of depression. The transcripts of the initial, middle and final psychotherapy sessions of 40 clients were analysed. A thematic analysis was conducted to identify what was occurring in the sessions, how the client was describing psychotherapy and how the client was describing improvement or lack of improvement in depressive symptoms. There were differences in descriptions of therapy and the experience of depression between clients who responded and those who did not respond to therapy that were related to improvement in symptoms but not to the specific therapy. These differences were in the client's engagement with the language of therapy, sense of optimism about the particular model of psychotherapy, ability to examine their own role in the problem and desire to engage with new ways of being in their lives. Clients who responded to CBT or IPT had flexibility to develop new ways of thinking and acting, the ability to accept responsibility for their role in the identified problem and were willing to risk change. PMID- 22070863 TI - European veterinary dissertations. PMID- 22070865 TI - Elimination versus ring opening: a convergent route to alkylidene-cyclobutanes. AB - Functionalized alkylidene-cyclobutanes have been prepared from 2-fluoropyridinyl 6-oxy precursors derived from vinyl cyclobutanols by a radical addition elimination process. A wide range of functional groups is tolerated, and the alkylidene-cyclobutanes can be further elaborated into cyclopentanones. The limitation of this approach resides in the competition with opening of the cyclobutane ring. PMID- 22070864 TI - American ginseng suppresses Western diet-promoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR. AB - BACKGROUND: Western diets increase colon cancer risk. Epidemiological evidence and experimental studies suggest that ginseng can inhibit colon cancer development. In this study we asked if ginseng could inhibit Western diet (20% fat) promoted colonic tumorigenesis and if compound K, a microbial metabolite of ginseng could suppress colon cancer xenograft growth. METHODS: Mice were initiated with azoxymethane (AOM) and, two weeks later fed a Western diet (WD, 20% fat) alone, or WD supplemented with 250-ppm ginseng. After 1 wk, mice received 2.5% dextran sulfate sodium (DSS) for 5 days and were sacrificed 12 wks after AOM. Tumors were harvested and cell proliferation measured by Ki67 staining and apoptosis by TUNEL assay. Levels of EGF-related signaling molecules and apoptosis regulators were determined by Western blotting. Anti-tumor effects of intraperitoneal compound K were examined using a tumor xenograft model and compound K absorption measured following oral ginseng gavage by UPLC-mass spectrometry. Effects of dietary ginseng on microbial diversity were measured by analysis of bacterial 16S rRNA. RESULTS: Ginseng significantly inhibited colonic inflammation and tumorigenesis and concomitantly reduced proliferation and increased apoptosis. The EGFR cascade was up-regulated in colonic tumors and ginseng significantly reduced EGFR and ErbB2 activation and Cox-2 expression. Dietary ginseng altered colonic microbial diversity, and bacterial suppression with metronidazole reduced serum compound K following ginseng gavage. Furthermore, compound K significantly inhibited tumor xenograft growth. CONCLUSIONS: Ginseng inhibited colonic inflammation and tumorigenesis promoted by Western diet. We speculate that the ginseng metabolite compound K contributes to the chemopreventive effects of this agent in colonic tumorigenesis. PMID- 22070866 TI - Volumetric modulated arc planning for lung stereotactic body radiotherapy using conventional and unflattened photon beams: a dosimetric comparison with 3D technique. AB - PURPOSE: Frequently, three-dimensional (3D) conformal beams are used in lung cancer stereotactic body radiotherapy (SBRT). Recently, volumetric modulated arc therapy (VMAT) was introduced as a new treatment modality. VMAT techniques shorten delivery time, reducing the possibility of intrafraction target motion. However dose distributions can be quite different from standard 3D therapy. This study quantifies those differences, with focus on VMAT plans using unflattened photon beams. METHODS: A total of 15 lung cancer patients previously treated with 3D or VMAT SBRT were randomly selected. For each patient, non-coplanar 3D, coplanar and non-coplanar VMAT and flattening filter free VMAT (FFF-VMAT) plans were generated to meet the same objectives with 50 Gy covering 95% of the PTV. Two dynamic arcs were used in each VMAT plan. The couch was set at +/- 5 degrees to the 0 degrees straight position for the two non-coplanar arcs. Pinnacle version 9.0 (Philips Radiation Oncology, Fitchburg WI) treatment planning system with VMAT capabilities was used. We analyzed the conformity index (CI), which is the ratio of the total volume receiving at least the prescription dose to the target volume receiving at least the prescription dose; the conformity number (CN) which is the ratio of the target coverage to CI; and the gradient index (GI) which is the ratio of the volume of 50% of the prescription isodose to the volume of the prescription isodose; as well as the V20, V5, and mean lung dose (MLD). Paired non-parametric analysis of variance tests with post-tests were performed to examine the statistical significance of the differences of the dosimetric indices. RESULTS: Dosimetric indices CI, CN and MLD all show statistically significant improvement for all studied VMAT techniques compared with 3D plans (p < 0.05). V5 and V20 show statistically significant improvement for the FFF-VMAT plans compared with 3D (p < 0.001). GI is improved for the FFF-VMAT and the non coplanar VMAT plans (p < 0.01 and p < 0.05 respectively) while the coplanar VMAT plans do not show significant difference compared to 3D plans. Dose to the target is typically more homogeneous in FFF-VMAT plans. FFF-VMAT plans require more monitor units than 3D or non-coplanar VMAT ones. CONCLUSION: Besides the advantage of faster delivery times, VMAT plans demonstrated better conformity to target, sharper dose fall-off in normal tissues and lower dose to normal lung than the 3D plans for lung SBRT. More monitor units are often required for FFF VMAT plans. PMID- 22070867 TI - Chronic cigarette smoking in alcohol dependence: associations with cortical thickness and N-acetylaspartate levels in the extended brain reward system. AB - Chronic smoking in alcohol dependence is associated with abnormalities in brain morphology and metabolite levels in large lobar regions (e.g. frontal lobe). Here, we evaluated if these abnormalities are specifically apparent in several cortical and select subcortical components of the extended brain reward system (BRS), a network that is critically involved in the development and maintenance of all forms of addictive disorders. We studied 33 non-smoking and 43 smoking alcohol-dependent individuals (ALC) with 1 week of abstinence and 42 non-smoking Controls. At 1.5 Tesla, we obtained regional measures of cortical thickness and N acetylaspartate (NAA; a surrogate marker of neuronal integrity) concentration in major components of the BRS as well as the corresponding measures throughout the cortex. Smoking ALC and non-smoking ALC demonstrated decreased thickness compared with Controls in the dorsolateral prefrontal cortex (DLPFC), insula, orbitofrontal cortex (OFC), the total BRS, total frontal cortex and global cortex. Smoking ALC had significantly decreased thickness compared to non-smoking ALC in the ACC, insula, the total BRS and total frontal cortex. Smoking ALC had also lower NAA concentrations than both non-smoking ALC and Controls in the DLPFC, insula, superior corona radiata and the total BRS. Alcohol consumption and common medical and psychiatric co-morbidities did not mediate differences between smoking and non-smoking ALC. This dual modality magnetic resonance (MR) study indicated that chronic smoking in ALC was associated with significant cortical thinning and NAA abnormalities in anterior brain regions that are implicated in the development and maintenance of addictive disorders. PMID- 22070868 TI - Immunogenicity of panitumumab in combination chemotherapy clinical trials. AB - BACKGROUND: Panitumumab is a fully human antibody against the epidermal growth factor receptor that is indicated for the treatment of metastatic colorectal cancer (mCRC) after disease progression on standard chemotherapy. The purpose of this analysis was to examine the immunogenicity of panitumumab and to evaluate the effect of anti-panitumumab antibodies on pharmacokinetic and safety profiles in patients with mCRC receiving panitumumab in combination with oxaliplatin- or irinotecan-based chemotherapies. METHODS: Three validated assays (two screening immunoassays and a neutralizing antibody bioassay) were used to detect the presence of anti-panitumumab antibodies in serum samples collected from patients enrolled in four panitumumab combination chemotherapy clinical trials. The impact of anti-panitumumab antibodies on pharmacokinetic and safety profiles was analyzed using population pharmacokinetic analysis and descriptive statistics, respectively. RESULTS: Of 1124 patients treated with panitumumab in combination with oxaliplatin- or irinotecan-based chemotherapy with postbaseline samples available for testing, 20 (1.8%) patients developed binding antibodies and 2 (0.2%) developed neutralizing antibodies. The incidence of anti-panitumumab antibodies was similar in patients with tumors expressing wild-type or mutant KRAS and in patients receiving oxaliplatin- or irinotecan-based chemotherapies. No evidence of an altered pharmacokinetic or safety profile was found in patients who tested positive for anti-panitumumab antibodies. CONCLUSIONS: The immunogenicity of panitumumab in the combination chemotherapy setting was infrequent and similar to the immunogenicity observed in the monotherapy setting. Panitumumab immunogenicity did not appear to alter pharmacokinetic or safety profiles. This low rate of immunogenicity may be attributed to the fully human nature of panitumumab. PMID- 22070869 TI - An allenic Pauson-Khand approach to 6,12-guaianolides. AB - Cyclocarbonylation of alpha-methylene butyrolactone-containing allene-ynes affords 6,12-guaianolide ring systems. Incorporation of the alpha-methylene butyrolactone early in a synthetic sequence is rare for reactivity reasons; however, this moiety proves to be beneficial to the allenic Pauson-Khand reaction. The three double bonds and the ketone in the resulting 5-7-5 ring system bear significant differences in their reactivity and are ideally positioned for synthetic application to 6,12-guaianolides and analogs. PMID- 22070870 TI - Assessment of carbon in woody plants and soil across a vineyard-woodland landscape. AB - BACKGROUND: Quantification of ecosystem services, such as carbon (C) storage, can demonstrate the benefits of managing for both production and habitat conservation in agricultural landscapes. In this study, we evaluated C stocks and woody plant diversity across vineyard blocks and adjoining woodland ecosystems (wildlands) for an organic vineyard in northern California. Carbon was measured in soil from 44 one m deep pits, and in aboveground woody biomass from 93 vegetation plots. These data were combined with physical landscape variables to model C stocks using a geographic information system and multivariate linear regression. RESULTS: Field data showed wildlands to be heterogeneous in both C stocks and woody tree diversity, reflecting the mosaic of several different vegetation types, and storing on average 36.8 Mg C/ha in aboveground woody biomass and 89.3 Mg C/ha in soil. Not surprisingly, vineyard blocks showed less variation in above and belowground C, with an average of 3.0 and 84.1 Mg C/ha, respectively. CONCLUSIONS: This research demonstrates that vineyards managed with practices that conserve some fraction of adjoining wildlands yield benefits for increasing overall C stocks and species and habitat diversity in integrated agricultural landscapes. For such complex landscapes, high resolution spatial modeling is challenging and requires accurate characterization of the landscape by vegetation type, physical structure, sufficient sampling, and allometric equations that relate tree species to each landscape. Geographic information systems and remote sensing techniques are useful for integrating the above variables into an analysis platform to estimate C stocks in these working landscapes, thereby helping land managers qualify for greenhouse gas mitigation credits. Carbon policy in California, however, shows a lack of focus on C stocks compared to emissions, and on agriculture compared to other sectors. Correcting these policy shortcomings could create incentives for ecosystem service provision, including C storage, as well as encourage better farm stewardship and habitat conservation. PMID- 22070871 TI - Benign paroxysmal vertigo of childhood: diagnostic value of vestibular test and high stimulus rate auditory brainstem response test. AB - OBJECTIVE: To investigate the diagnostic value of vestibular test and high stimulus rate auditory brainstem response (ABR) test and the possible mechanism responsible for benign paroxysmal vertigo of childhood (BPVC). METHODS: Data of 56 patients with BPVC in vertigo clinic of our hospital from May 2007 to September 2008 were retrospectively analyzed in this study. Patients with BPVC were tested with pure tone audiometry, high stimulus rate auditory brainstem response test (ABR), transcranial Doppler sonography (TCD), bithermal caloric test, and VEMP. The results of the hearing and vestibular function test were compared and analyzed. RESULTS: There were 56 patients with BPVC, including 32 men, 24 women, aged 3-12 years old, with an average of 6.5 years. Among 56 cases of BPVC patients, the results of pure tone audiometry were all normal. High stimulus rate ABR was abnormal in 66.1% (37/56) of cases. TCD showed 57.1% abnormality in 56 cases, including faster flow rate in 28 cases and slower flow rate in 4 cases. High stimulus rate ABR and TCD were both abnormal in 48.2% (27/56) of cases. Bithermal caloric test was abnormal in 14.3% (8/56) of cases. VEMP showed 32.1% abnormality, including amplitude abnormality in 16 cases and latency abnormality in 2 cases. The abnormal rate of VEMP was much higher than that of caloric test. CONCLUSION: Vascular mechanisms might be involved in the pathogenesis of BPVC and there is strong evidence for close relationship between BPVC and migraine. High stimulus rate ABR is helpful in the diagnosis of BPVC. The inferior vestibular pathway is much more impaired than the superior vestibular pathway in BPVC. PMID- 22070872 TI - Prevalence of mutations located at the dfnb1 locus in a population of cochlear implanted children in eastern Romania. AB - OBJECTIVE: Hearing loss is one of the major public health problems, with a genetic etiology in more than 60% of cases. Connexin 26 and connexin 30 mutations are the most prevalent causes of deafness. The aim of this study is to characterize and to establish the prevalence of the GJB2 and GJB6 gene mutations in a population of cochlear implanted recipients from Eastern Romania, this being the first report of this type in our country. METHODS: We present a retrospective study that enrolled 45 Caucasian cochlear implanted patients with non-syndromic sensorineural severe to profound, congenital or progressive with early-onset idiopathic hearing loss. We performed sequential analysis of exon 1 and the coding exon 2 of the GJB2 gene including also the splice sites and analysis of the deletions del(GJB6-D13S1830), del(GJB6-D13S1854) and del(chr13:19,837,343 19,968,698). RESULTS: The genetic analysis of the GJB2 gene identified connexin 26 mutations in 22 patients out of 45 (12 homozygous for c.35delG, 6 compound heterozygous and 4 with mutations only on one allele). We found 6 different mutations, the most prevalent being c.35delG - found on 32 alleles, followed by p.W24* - found on 2 alleles. We did not identify the deletions del(GJB6 D13S1830), del(GJB6-D13S1854) and del(chr13:19,837,343-19,968,698). CONCLUSIONS: Although the most prevalent mutation was c.35delG (80% from all types of mutations), unexpectedly we identified 5 more different mutations. The presence of 6 different mutations on the GJB2 gene has implications in hearing screening programs development in our region and in genetic counseling. PMID- 22070873 TI - Differential role of NF-kappaB, ERK1/2 and AP-1 in modulating the immunoregulatory functions of bone marrow-derived dendritic cells from NOD mice. AB - Tolerogenic dendritic cells represent a promising immunotherapy in autoimmunity. However, the molecular mechanisms that drive tolerogenic DCs functions are not well understood. We used GM-CSF or GM-CSF+IL-4 to generate tolerogenic (GM/DCs) and immunogenic (IL-4/DCs) BMDCs from NOD mice, respectively. GM/DCs were resistant to maturation, produced large amounts of IL-10 but not IL-12p70. GM/DCs displayed a reduced capacity to activate diabetogenic CD8(+) T-cells and were efficient to induce Tregs expansion and conversion. LPS stimulation triggered ERK1/2 activation that was sustained in GM/DCs but not in IL-4/DCs. ERK1/2 and AP 1 were involved in IL-10 production in GM/DCs but not in their resistance to maturation. Supershift analysis showed that NF-kappaB DNA binding complex contains p52 and p65 in GM/DCs, whereas it contains p52, p65 and RelB in IL 4/DCs. ChIP experiments revealed that p65 was recruited to IL-10 promoter following LPS stimulation of GM/DCs whereas its binding to IL-12p35 promoter was abolished. Our results suggest that immunoregulatory functions of GM/DCs are differentially regulated by ERK1/2, AP-1 and NF-kappaB pathways. PMID- 22070875 TI - Emphysematous pyelonephritis in a renal allograft. PMID- 22070874 TI - CXCR7 mediated Gialpha independent activation of ERK and Akt promotes cell survival and chemotaxis in T cells. AB - Chemokine receptors CXCR7 and CXCR4 bind to the same ligand stromal cell derived factor-1alpha (SDF-1alpha/CXCL12). We assessed the downstream signaling pathways mediated by CXCL12-CXCR7 interaction in Jurkat T cells. All experiments were carried out after functionally blocking the CXCR4 receptor. CXCL12, on binding CXCR7, induced phosphorylation of extra cellular regulated protein kinases (ERK 1/2) and Akt. Selective inhibition of each signal demonstrated that phosphorylated ERK 1/2 is essential for chemotaxis and survival of T cells whereas activation of Akt promotes only cell survival. Another interesting finding of this study is that CXCL12-CXCR7 interaction under normal physiological conditions does not activate the p38 pathway. Furthermore, we observed that the CXCL12 signaling via CXCR7 is Gialpha independent. Our findings suggest that CXCR7 promotes cell survival and does not induce cell death in T cells. The CXCL12 signaling via CXCR7 may be crucial in determining the fate of the activated T cells. PMID- 22070876 TI - An unusual case of hypotension after fibrinolysis resulting from mediastinal hemorrhage. AB - BACKGROUND: Although bleeding complications may occur after fibrinolysis, mediastinal hemorrhage is extremely rare. CASE REPORT: We encountered mediastinal hemorrhage in a case of anterior wall myocardial infarction (MI); the patient developed sudden-onset chest pain with hypotension after fibrinolysis. The differential diagnosis and approach to management of such a case is discussed. CONCLUSION: As fibrinolysis remains a common means of establishing reperfusion in patients with acute MI, emergency physicians should be aware of such unusual complications secondary to fibrinolysis. An orderly clinical approach with an individualized management protocol is essential in such situations so that undue instrumentation and invasive procedures with their attendant risks in a thrombolysed patient are avoided. PMID- 22070877 TI - Understanding of sepsis among emergency medical services: a survey study. AB - BACKGROUND: Emergency medical services (EMS) personnel commonly encounter sepsis, yet little is known about their understanding of sepsis. STUDY OBJECTIVES: To determine the awareness, knowledge, current practice, and attitudes about sepsis among EMS personnel. METHODS: We performed an anonymous, multi-agency, online survey of emergency medical technicians (EMTs), firefighter-emergency medical technicians (FF-EMTs), and paramedics in a metropolitan, 2-tier EMS system. We compared responses according to the level of EMS training and used multivariable logistic regression to determine the odds of correctly identifying the definition of sepsis, independent of demographic and professional factors. RESULTS: Overall response rate of study participants was 57% (786/1390), and was greatest among EMTs (79%; 276/350). A total of 761 respondents (97%) had heard of the term "sepsis." EMTs and FF-EMTs were at significantly reduced odds of correctly defining sepsis compared to paramedics, independent of age, sex, and years of experience (EMTs: odds ratio 0.44, 95% confidence interval 0.3-0.8; FF-EMTs: odds ratio 0.32, 95% confidence interval 0.2-0.6. Overall, knowledge of the clinical signs and symptoms and recommended treatments for sepsis was typically>75%, though better among paramedics than EMTs or FF-EMTs (p<0.01). The majority of respondents believed sepsis is not recognized by EMS "some" or "a lot" of the time (76%, 596/786). CONCLUSIONS: EMS personnel demonstrated an overall sound awareness of sepsis. Knowledge of sepsis was less among FF-EMTs and EMTs compared to paramedics. These results suggest that paramedics could be integrated into strategies of early identification and treatment of sepsis, and EMTs may benefit from focused education and training. PMID- 22070878 TI - Hyperdense basilar sign: an early computed tomography finding of acute ischemia. PMID- 22070879 TI - Acute sphenoid sinusitis induced blindness: a case report. AB - BACKGROUND: Acute, isolated sphenoid sinusitis is a rare but potentially devastating clinical entity. Missing this diagnosis can lead to permanent vision loss due to injury of the optic nerve. Patients may present with preseptal inflammation, lid edema, chemosis, or ophthalmoplegia. OBJECTIVE: We report a case of acute sphenoid sinusitis in a 10-year-old child who presented to the Emergency Department with essentially painless vision loss. CASE REPORT: Previously healthy, the patient reported progressive decrease in vision in her right eye for the 5 days prior. Other than blurred vision in the right eye, she complained of a mild frontal headache and right eye irritation the past week, which had abated. On examination, she was reading a book with her head tilted to one side. She had no photophobia, or facial or eyelid swelling. Her pupils were 5 mm bilaterally, but the right was non-reactive to light. She was unable to see two fingers 6 inches in front of her face (right eye), whereas her visual acuity on the left was 20/25. She had bilateral elevated intraocular pressures and a Marcus Gunn pupil on the right. Ophthalmology was consulted and the diagnosis of acute sphenoid sinusitis causing compression and vascular compromise to the optic nerve was diagnosed ultimately by magnetic resonance imaging. The patient was transferred to the nearest pediatric specialty hospital, where an emergent endoscopic sphenoidotomy was performed. The patient's vision subsequently returned. CONCLUSION: Sphenoid sinusitis should be considered in patients presenting with acute vision loss. Awareness, early diagnosis, and intervention help prevent permanent complications. PMID- 22070880 TI - Quality of human-computer interaction--results of a national usability survey of hospital-IT in Germany. AB - BACKGROUND: Due to the increasing functionality of medical information systems, it is hard to imagine day to day work in hospitals without IT support. Therefore, the design of dialogues between humans and information systems is one of the most important issues to be addressed in health care. This survey presents an analysis of the current quality level of human-computer interaction of healthcare-IT in German hospitals, focused on the users' point of view. METHODS: To evaluate the usability of clinical-IT according to the design principles of EN ISO 9241-10 the IsoMetrics Inventory, an assessment tool, was used. The focus of this paper has been put on suitability for task, training effort and conformity with user expectations, differentiated by information systems. Effectiveness has been evaluated with the focus on interoperability and functionality of different IT systems. RESULTS: 4521 persons from 371 hospitals visited the start page of the study, while 1003 persons from 158 hospitals completed the questionnaire. The results show relevant variations between different information systems. CONCLUSIONS: Specialised information systems with defined functionality received better assessments than clinical information systems in general. This could be attributed to the improved customisation of these specialised systems for specific working environments. The results can be used as reference data for evaluation and benchmarking of human computer engineering in clinical health IT context for future studies. PMID- 22070881 TI - The immediate lifesaving management of maxillofacial, life-threatening haemorrhages due to IED and/or shrapnel injuries: "when hazard is in hesitation, not in the action". AB - Maxillofacial/neck vascular injuries caused by improvised explosive devices IEDs or ballistics injuries are life threatening when they cause severe haemorrhage resulting in airway compromise. One should always keep in mind that the best technique used is that which saves the patient's life and not the most expensive and/or technologically advanced. Medical professionals on the scene should have the necessary experience to handle the emergency situations of airway compromise and haemorrhage control. In this instance there is only, "one to a few minutes" to clear airway obstruction and arrest haemorrhage to prevent death. The patients in this study had life-threatening shrapnel injuries of the carotid and/or jugular vessels, and facial primary blast affect implosion of facial middle third air-containing cavities injuries. In a massive casualties arenas, where time=lifesaving, we should need to replace "non-battlefield" civilian techniques with "time driven", combat management for IEDs injuries. In these cases, the immediate and effective compression tamponade using digital, Foley catheter tamponade, packs and/or vessels ligation for severe facial/neck haemorrhage were used successfully. PMID- 22070882 TI - Crystallography Open Database (COD): an open-access collection of crystal structures and platform for world-wide collaboration. AB - Using an open-access distribution model, the Crystallography Open Database (COD, http://www.crystallography.net) collects all known 'small molecule / small to medium sized unit cell' crystal structures and makes them available freely on the Internet. As of today, the COD has aggregated ~150,000 structures, offering basic search capabilities and the possibility to download the whole database, or parts thereof using a variety of standard open communication protocols. A newly developed website provides capabilities for all registered users to deposit published and so far unpublished structures as personal communications or pre publication depositions. Such a setup enables extension of the COD database by many users simultaneously. This increases the possibilities for growth of the COD database, and is the first step towards establishing a world wide Internet-based collaborative platform dedicated to the collection and curation of structural knowledge. PMID- 22070884 TI - Wnt3 gene expression promotes tumor progression in non-small cell lung cancer. AB - The Wnt gene family encodes the multi-functional signaling glycoproteins regulating various normal and pathological processes including tumorigenesis. We investigated the clinical significance of the Wnt3 gene expression in relation to its target genes, c-Myc and survivin, in patients with non-small cell lung cancer (NSCLC). One hundred and twenty-eight patients who underwent resection of NSCLC were analyzed. Quantitative reverse transcription polymerase chain reaction (RT PCR) was performed to evaluate the gene expression of Wnt3, c-Myc, and survivin. Immunohistochemistry was performed to investigate the protein expression of Wnt3, c-Myc, and survivin. The Ki-67 proliferation index and the apoptotic index using the TUNEL method were also evaluated. Twenty-four carcinomas (18.8%) were found to be high-Wnt3 tumors. The high-Wnt3 tumors were significantly more in squamous cell carcinomas than that in adenocarcinomas (P=0.0022). The Wnt3 gene expression was significantly associated with gene expressions of c-Myc (P=0.0103) and survivin (P=0.0009). As a result, the Ki-67 proliferation index was significantly higher in high-Wnt3 tumors than in low-Wnt3 tumors (P=0.0056). The apoptotic index was significantly lower in high-Wnt3 tumors than in low-Wnt3 tumors (P=0.0245). The overall survival rate was significantly lower in patients with high-Wnt3 tumors than in those with low-Wnt3 tumors (P=0.0020). A Cox regression analysis demonstrated that the Wnt3 status was a significant prognostic factor for NSCLC patients (hazard ratio 2.226, P=0.0296). The present study revealed that Wnt3 gene expression was significantly associated with c-Myc and survivin gene expressions, tumor proliferation, and tumor apoptosis. During the progression of NSCLC, Wnt3 overexpression could be associated with the development of more aggressive tumors. PMID- 22070883 TI - Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs. AB - Anti-miRs are oligonucleotide inhibitors complementary to miRNAs that have been used extensively as tools to gain understanding of specific miRNA functions and as potential therapeutics. We showed previously that peptide nucleic acid (PNA) anti-miRs containing a few attached Lys residues were potent miRNA inhibitors. Using miR-122 as an example, we report here the PNA sequence and attached amino acid requirements for efficient miRNA targeting and show that anti-miR activity is enhanced substantially by the presence of a terminal-free thiol group, such as a Cys residue, primarily due to better cellular uptake. We show that anti-miR activity of a Cys-containing PNA is achieved by cell uptake through both clathrin dependent and independent routes. With the aid of two PNA analogues having intrinsic fluorescence, thiazole orange (TO)-PNA and [bis-o (aminoethoxy)phenyl]pyrrolocytosine (BoPhpC)-PNA, we explored the subcellular localization of PNA anti-miRs and our data suggest that anti-miR targeting of miR 122 may take place in or associated with endosomal compartments. Our findings are valuable for further design of PNAs and other oligonucleotides as potent anti-miR agents. PMID- 22070885 TI - Intra-articular osteoid osteoma of the hip misdiagnosed by MRI: an unusual cause of unexplained hip pain. AB - Osteoid osteoma is a common benign bone tumor affecting the young adult with typical clinical and radiographic presentation in its most common locations. However, when arising in unusual intra-articular locations, diagnosis may appear confusing and lead to delayed management. We present the case of a 24-year-old man with intra-articular osteoid osteoma of the hip involving the posteroinferior quarter of the femoral head. This unusual location was at the origin of unexplained pain and delayed diagnosis made 18 months after the onset of symptoms since the initial magnetic resonance imaging (MRI) examination could not identify the lesion whereas it was detected on bone scintigraphy and thin slice CT imaging. Due to the complex location providing difficult access for radioguided techniques, an open surgical management was suggested and performed through a limited posterolateral approach with no hip dislocation, after identification of the circumflex pedicle. Following complete surgical excision of the tumor, the diagnosis could be confirmed after histopathologic analysis. No recurrence was observed. PMID- 22070886 TI - Perverse political correctness and personality traits. AB - Political correctness (PC) commonly refers to a mutual respect for the views and beliefs of others, including enemies, and while differing in opinions, the willfulness to overcome the existing disagreements, and to prevent animosity. To date however, the term PC is sometimes used in a perverted sense aimed for disintegration of solidarity in a society, thus giving birth to a new powerful conceptual tool, the perverse political correctness (PPC). PPC ideology resides in people with certain psychological types. We assume that there are basic psychological variations of personality traits and the mechanisms of their formation that promote not only insertion, but rapid distribution of modern PPC ideology. Although the dimension of their behavior is very similar, the personality traits of these persons can be divided into three groups: The subjects from the first group are characterized by general traits of one's personality, such as kindness, empathy, and humanism. This is true PC--an expression of proper humanistic personality traits, which are developed in a specific kind of environment. The subjects from second group are usually artistic, theatrical, vain and narcissistic, poseurs who need attention at any cost. Their views on life in general, as well as on questions of PC are characterized by colorfulness, picturesqueness and emotional satiety. The subjects from the third group, conjoined with the previous variety of demonstrative-theatrical PC, use mystical and religious contents as part of their propaganda of PPC activity. PMID- 22070887 TI - Aspirin may do wonders by the induction of immunological self-tolerance against autoimmune atherosclerosis. AB - Induction of immune tolerance is one of the recent novel immunomodulatory strategies to directly intervene the autoimmune-driven atherosclerosis. Aspirin is a prototypic non-steroidal anti-inflammatory drug, which is now being regarded as a life-saver in variety of atherosclerotic cardiovascular complications. Considerable amount of data emerged during last few years clearly suggests that aspirin can cause immunomodulation by several mechanisms, particularly, its ability to induce tolerogenic dendritic cells (DCs) and to upregulate T regulatory (Treg) cells is especially appealing with respect to induction of immunological self-tolerance. Based on this fact, we hypothesize that aspirin, in addition to its anti-inflammatory effect, may also specifically inhibit autoimmune response in atherosclerosis by actively increasing CD4+CD25+FOXP3+Treg cells as well as by inducing tolerogenic DCs which induce hyporesponsiveness in responder naive T cells. If proved to be correct, this hypothesis will provide an opportunity to medical community with an already available aspirin-based immunotherapeutic approach for inducing immune tolerance against atherosclerosis. PMID- 22070888 TI - The existence of two types of proteasome, the constitutive proteasome and the immunoproteasome, may serve as another layer of protection against autoimmunity. AB - Negative selection of CD8 single positive thymocytes is based on the presentation through the major histocompatibility complex (MHC) class I pathway of peptides derived from degradation of self-proteins by the constitutive proteasome and the immunoproteasome in the thymus. Then naive CD8+ T-cells can be primed by mature dendritic cells. In mature dendritic cells peptides presented by MHC class I molecules are derived from degradation of endogenous self-proteins or through the process of cross-presentation from degradation of exogenous proteins by the immunoproteasome. In the absence of infection, peripheral cells display peptides on MHC class I molecules derived from degradation of endogenous self-proteins by the constitutive proteasome. The pool of peptides derived from protein degradation by the constitutive proteasome differs from the pool peptides derived from protein degradation by the immunoproteasome. Thus the probability of an autoreactive naive CD8+ T-cell that escaped negative selection, and converted by a mature dendritic cell to autoreactive cytolytic T-cell, to kill a normal cell in the periphery, is reduced. PMID- 22070889 TI - PathCase-SB architecture and database design. AB - BACKGROUND: Integration of metabolic pathways resources and regulatory metabolic network models, and deploying new tools on the integrated platform can help perform more effective and more efficient systems biology research on understanding the regulation in metabolic networks. Therefore, the tasks of (a) integrating under a single database environment regulatory metabolic networks and existing models, and (b) building tools to help with modeling and analysis are desirable and intellectually challenging computational tasks. DESCRIPTION: PathCase Systems Biology (PathCase-SB) is built and released. The PathCase-SB database provides data and API for multiple user interfaces and software tools. The current PathCase-SB system provides a database-enabled framework and web based computational tools towards facilitating the development of kinetic models for biological systems. PathCase-SB aims to integrate data of selected biological data sources on the web (currently, BioModels database and KEGG), and to provide more powerful and/or new capabilities via the new web-based integrative framework. This paper describes architecture and database design issues encountered in PathCase-SB's design and implementation, and presents the current design of PathCase-SB's architecture and database. CONCLUSIONS: PathCase-SB architecture and database provide a highly extensible and scalable environment with easy and fast (real-time) access to the data in the database. PathCase-SB itself is already being used by researchers across the world. PMID- 22070890 TI - The factor structure of the Chinese family assessment instrument adapted for parent report. AB - This article reports on a confirmatory factor analytic study of an adapted version of an instrument designed to assess family functioning of Chinese families. The Chinese Family Assessment Instrument, originally designed for completion by adolescents, was adapted for completion by parents. A sample of 700 parent dyads of elementary school children (382 girls and 318 boys) completed the adapted questionnaire. Initial factor analyses showed that the existing five factor structure used for adolescents' responses was not a good fit for these data. Instead, a four-factor solution emerged where the factors were positive family functioning, negative family functioning, tolerance for family members, and parental understanding. This structure was the same for both mothers and fathers. Further studies of the Chinese Family Assessment Instrument parent adaptation are required to test the factor structure that emerged. Following such studies, validation studies will be required. PMID- 22070891 TI - Critical appraisal of World Health Organization's new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. AB - In 2010, the World Health Organization established new reference values for human semen characteristics that are markedly lower than those previously reported. Despite using controlled studies involving couples with a known time to pregnancy to establish the new limits, the reference studies are limited with regard to the population analyzed and the methods used for semen evaluation. The present review discusses concerns related to the new reference values for semen characteristics, including the effect on patient referral, diagnosis, and treatment of recognized conditions, such as varicocele, and on the indications for assisted reproductive technologies. PMID- 22070892 TI - Effect of warm ischemia on renal function during partial nephrectomy: assessment with new 99mTc-mercaptoacetyltriglycine scintigraphy parameter. AB - OBJECTIVE: A decrease in renal function after partial nephrectomy caused by ischemic damage or nephron loss cannot be distinguished by conventional methods. We quantified renal function using a new 99mTc-mercaptoacetyltriglycine (99mTc MAG3) renal scintigraphy parameter. MATERIAL AND METHODS: We included 32 patients with a normally functioning contralateral kidney who received open partial nephrectomy with average warm ischemic time of 26.0 (range 14-46) min in this study. Effective renal plasma flow (ERPF) was calculated from 99mTc-MAG3 renal scintigraphy before and at 1 week and 6 months after surgery. We also analyzed regional 99mTc-MAG3 uptake in the surgically nonaffected parts. RESULTS: One week after surgery, average ERPF in the operated kidney decreased to 66.4% from baseline (from 177.8 to 116.9 mL/min/1.73 m2) and regional 99mTc-MAG3 uptake decreased to 83.4%. A stronger correlation was found between ischemic time and the decrease in regional 99mTc-MAG3 uptake (P<.001) compared with ERPF (P=.029). The decrease in regional 99mTc-MAG3 uptake remained at 6 months in the group with ischemic time>=25 minutes, whereas it recovered when ischemic time was <25 minutes. CONCLUSION: This new parameter quantified ischemic renal damage better than the conventional split functional evaluation. When warm ischemic time was >=25 minutes, irreversible diffuse damage was seen in surgically preserved nephrons. PMID- 22070893 TI - A Chinese herbal formula, Shuganyiyang capsule, improves erectile function in male rats by modulating Nos-CGMP mediators. AB - OBJECTIVE: To evaluate the effects of the Chinese herbal formula Shuganyiyang (SGYY) capsule on arteriogenic erectile dysfunction (ED) in a rat model and to investigate the underlying molecular mechanism. METHODS: Forty male Sprague Dawley rats were subjected to bilateral ligation of the internal iliac artery and then divided into 4 groups (n=10 per group). They were treated daily with either sildenafil (10.5 mg/kg), or SGYY at 1 of 2 dosages (1 g/kg and 0.5 g/kg) for 30 days. Erectile function was evaluated using cavernous nerve electrical stimulation after treatment, and the cavernous tissue specimens of all animals were harvested for gene and protein examination using real-time reverse transcriptase polymerase chain reaction, Western blot analysis, and cyclic guanosine monophosphate (cGMP) measurement. RESULTS: The ratio of the maximal intracavernous pressure to the mean arterial pressure was significantly higher in the SGYY (1 g/kg and 0.5 g/kg) rats than that in the models (P<.01). The gene and protein expression of 3 subtypes of nitric oxide synthase (NOS)--neuropathic (nNOS), inducible (iNOS), and endothelial (eNOS)--and cGMP concentrations in cavernous tissue in SGYY-treated rats were significantly higher than in the models. However, phosphodiesterase type 5 (PDE5) expression in the SGYY rats was lower than those in models (P<.01 or P<.05). CONCLUSION: SGYY significantly improves the maximal intracavernous pressure in arteriogenic ED in a rat model. The underlying mechanism of action of SGYY involves increasing the expression of some main factors in the NOS-cGMP pathway and reducing the expression of PDE5. PMID- 22070894 TI - SIU Scholar: Dr. Fahed Abdullah Salem Baaboud. PMID- 22070895 TI - Pilot study of the vesicocutaneous continent catheterizable stoma (mitrofanoff) in adults--high complication rates. AB - OBJECTIVE: To report our experience with an adult vesicocutaneous Mitrofanoff, an alternative to standard appendiceal or ileal Mitrofanoff. MATERIAL AND METHODS: Retrospective chart review was performed on 3 patients who underwent a vesicocutaneous Mitrofanoff by a single surgeon. Data were collected on etiology, complications, and number of procedures to correct the complication. RESULTS: Indications for the procedure included neurogenic bladder and urinary retention. Mean follow-up time was 485 days with mean time to first complication of 24 days. One-hundred percent of patients saw stenosis and dehiscence of their wounds. All 3 patients required subsequent surgery. Sixty-six percent required reoperation to the standard Mitrofanoff with a mean time to this procedure of 222 days. The mean number of procedures was 4 (range 2-6). CONCLUSION: Continent catheterizable stomas have been a continuous challenge for adults who have had multiple abdominal surgeries, making a typical appendix, ureter, or small bowel Mitrofanoff difficult. We looked at our experience with a cutaneous Mitrofanoff (an extraperitoneal procedure often done in pediatrics but never before in adults) as an alternative but found complication rates of 100%. These included stenosis and dehiscence eventually requiring reoperation, with some even requiring conversion to an ileal or appendiceal Mitrofanoff. Although there are high complication rates in the standard Mitrofanoff, we conclude that a vesicocutaneous Mitrofanoff is not an effective alternative. PMID- 22070896 TI - Gold nanoparticle probes: design and in vitro applications in cancer cell culture. AB - A new architecture has been designed by the conjugation of [(18)F]2-fluoro-2 deoxy-D-glucose ((18)F-FDG), gold nanoparticles (AuNPs), and anti-metadherin (Anti-MTDH) antibody which is specific to the metadherin (MTDH) over-expressed on the surface of breast cancer cells. Mannose triflate molecule is used as a precursor for synthesis of (18)F-FDG by nucleophilic fluorination. For the conjugation of (18)F-FDG and AuNPs, cysteamine was first bound to mannose triflate (Man-CA) before synthesizing of (18)F-FDG which has cysteamine sides ((18)FDG-CA). Then, (18)FDG-CA was reacted with HAuCl(4) to obtain AuNPs and with NaBH(4) for reduction of AuNPs. At the end of this procedure, AuNPs were conjugated to (18)F-FDG via disulphide bonds ((18)FDG-AuNP). For the conjugation of Anti-MTDH, 1,1'-carbonyl diimidazol (CDI) was bound to the (18)FDG-AuNP, and Anti-MTDH was conjugated via CDI ((18)FDG-AuNP-Anti-MTDH). This procedure was also performed by using Na(19)F to obtain non-radioactive conjugates ((19)FDG AuNP-Anti-MTDH). Scanning electron microscopy (SEM) images demonstrated that synthesized particles were in nano sizes. (18)FDG-AuNP-Anti-MTDH conjugate was characterized and used as a model probe containing both radioactive and optical labels together as well as the biological target. The (18)FDG-AuNP-Anti-MTDH conjugate was applied to MCF7 breast cancer cell line and apoptotic cell ratio was found to be increasing from 2% to 20% following the treatment. Hence, these results have promised an important application potential of this conjugate in cancer research. PMID- 22070897 TI - Anti-fouling surfaces by combined molecular self-assembly and surface-initiated ATRP for micropatterning active proteins. AB - A simple method by combined molecular self assembly and surface-initiated atom transfer radical polymerization (SI-ATRP) was proposed to prepare a biologically inert surface for micropatterning active proteins. The MPEG microdomains having a short terminal poly(ethylene glycol) (PEG) unit were prepared by self assembly of 2-(methyoxy(polyethylenoxy) propyl)trimethoxy silane (MPEG-silane). The remaining local regions or poly(poly(ethylene glycol)methyl ether methacrylate-co-glycidyl methacrylate) (P(PEGMEMA-co-GMA)) microdomains were produced via SI-ATRP of PEGMEMA and GMA comonomers. The epoxy groups of the P(PEGMEMA-co-GMA) microdomains were used directly for covalent coupling of an active protein (human immunoglobulin or IgG) via the ring-opening reaction to produce the IgG-coupled microdomains. The IgG-coupled microdomains interact only and specifically with target anti-IgG, while the other antifouling microregions from self-assembled monolayers with short terminal PEG units effectively prevent specific and non specific protein fouling. When extended to other active biomolecules, microarrays for specific and non-specific analyte interactions with a high signal-to-noise ratio could be readily tailored. PMID- 22070898 TI - Definition of acute insomnia: diagnostic and treatment implications. PMID- 22070899 TI - The antimicrobial activity of photodynamic therapy against Streptococcus mutans using different photosensitizers. AB - Several photosensitizers have been used against oral bacteria without standardization. Singlet oxygen ((1)O(2)) is an aggressive chemical species that can kill cells through apoptosis or necrosis. OBJECTIVE: to compare the antimicrobial activity of photodynamic therapy (PDT) with different photosensitizers at the same concentration against Streptococcus mutans. In addition, the (1)O(2) production of each photosensitizer was determined. The photosensitizers (163.5 MUM) methylene blue (MB), toluidine blue ortho (TBO) and malachite green (MG) were activated with a light-emitting diode (LED; lambda=636 nm), while eosin (EOS), erythrosine (ERI) and rose bengal (RB) were irradiated with a curing light (lambda=570 nm). Light sources were operated at 24 J cm(-2). For each photosensitizer, 40 randomized assays (n=10 per condition) were performed under one of the following experimental conditions: no light irradiation or photosensitizer, irradiation only, photosensitizer only or irradiation in the presence of a photosensitizer. After treatment, serial dilutions of S. mutans were seeded onto brain heart infusion agar to determine viability in colony-forming units per milliliter (CFU mL(-1)). Generation of (1)O(2) was analyzed by tryptophan photooxidation, and the decay constant was estimated. Results were analyzed by one-way ANOVA and the Tukey-Kramer test (p<0.05). PDT with irradiation in the presence of the photosensitizers TBO and MG was effective in reducing S. mutans counts by 3 and 1.4 logs, respectively (p<0.01), compared to their respective untreated controls. MB generated 1.3 times more (1)O(2) than TBO, and both produced significantly higher concentrations of singlet oxygen than the other photosensitizers. Since in vitro bulk (1)O(2) production does not indicate that (1)O(2) was generated in the bacterial activity site, the bactericidal action against S. mutans cannot be related to in vitro singlet O(2) generation rate. In vitroS. mutans-experiments demonstrated TBO as the only photosensitizer that effectively reduced 99.9% of these microorganisms. PMID- 22070900 TI - Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes. AB - Hydrogen-rich electrolyzed warm water (HW) was prepared at 41 degrees C and exhibited dissolved hydrogen (DH) of 1.13 ppm and an oxidation-reduction potential (ORP) of -741 mV in contrast to below 0.01 ppm and+184 mV for regular warm water (RW). Fibroblasts OUMS-36 and keratinocytes HaCaT were used to examine effects of HW against UVA-ray irradiation. Type-I collagen was synthesized 1.85- to 2.03-fold more abundantly by HW application for 3-5 days than RW in OUMS-36 fibroblasts, and localized preferentially around the nuclei as shown by immunostain. HW application significantly prevented cell death and DNA damages such as nuclear condensation and fragmentation in UVA-irradiated HaCaT keratinocytes as estimated by WST-1 and Hoechst 33342 assays. HW significantly suppressed UVA-induced generation of intracellular superoxide anion radicals in both the cell lines according to NBT assay. Wrinkle repression was clinically assessed using a HW-bathing. Six Japanese subjects were enrolled in a trial of HW bathing (DH, 0.2-0.4 ppm) every day for 3 months. HW-bathing significantly improved wrinkle in four subjects on the back of neck on 90th day as compared to 0 day. Thus, HW may serve as daily skin care to repress UVA-induced skin damages by ROS-scavenging and promotion of type-I collagen synthesis in dermis. PMID- 22070903 TI - Do we need a global strategy for microbial conservation? PMID- 22070902 TI - Influence of race and socioeconomic status on engagement in pediatric primary care. AB - OBJECTIVE: To understand the association of race/ethnicity with engagement in pediatric primary care and examine how any racial/ethnic disparities are influenced by socioeconomic status. METHODS: Visit videos and parent surveys were obtained for 405 children who visited for respiratory infections. Family and physician engagement in key visit tasks (relationship building, information exchange, and decision making) were coded. Two parallel regression models adjusting for covariates and clustering by physician were constructed: (1) race/ethnicity only and (2) race/ethnicity with SES (education and income). RESULTS: With and without adjustment for SES, physicians seeing Asian families spoke 24% fewer relationship building utterances, compared to physicians seeing White, non-Latino families (p<0.05). Latino families gathered 24% less information than White, non-Latino families (p<0.05), but accounting for SES mitigates this association. Similarly, African American families were significantly less likely to be actively engaged in decision making (OR=0.32; p<0.05), compared to White, non-Latino families, but adjusting for SES mitigated this association. CONCLUSION: While engagement during pediatric visits differed by the family's race/ethnicity, many of these differences were eliminated by accounting for socioeconomic status. PRACTICE IMPLICATIONS: Effective targeting and evaluation of interventions to reduce health disparities through improving engagement must extend beyond race/ethnicity to consider socioeconomic status more broadly. PMID- 22070901 TI - Split-protein systems: beyond binary protein-protein interactions. AB - It has been estimated that 650,000 protein-protein interactions exist in the human interactome (Stumpf et al., 2008), a subset of all possible macromolecular partnerships that dictate life. Thus there is a continued need for the development of sensitive and user-friendly methods for cataloguing biomacromolecules in complex environments and for detecting their interactions, modifications, and cellular location. Such methods also allow for establishing differences in the interactome between a normal and diseased cellular state and for quantifying the outcome of therapeutic intervention. A promising approach for deconvoluting the role of macromolecular partnerships is split-protein reassembly, also called protein fragment complementation. This approach relies on the appropriate fragmentation of protein reporters, such as the green fluorescent protein or firefly luciferase, which when attached to possible interacting partners can reassemble and regain function, thereby confirming the partnership. Split-protein methods have been effectively utilized for detecting protein protein interactions in cell-free systems, Escherichia coli, yeast, mammalian cells, plants, and live animals. Herein, we present recent advances in engineering split-protein systems that allow for the rapid detection of ternary protein complexes, small molecule inhibitors, as well as a variety of macromolecules including nucleic acids, poly(ADP) ribose, and iron sulfur clusters. We also present advances that combine split-protein systems with chemical inducers of dimerization strategies that allow for regulating the activity of orthogonal split-proteases as well as aid in identifying enzyme inhibitors. Finally, we discuss autoinhibition strategies leading to turn-on sensors as well as future directions in split-protein methodology including possible therapeutic approaches. PMID- 22070904 TI - Change in binge eating and binge eating disorder associated with migration from Mexico to the U.S. AB - Exposure to Western popular culture is hypothesized to increase risk for eating disorders. This study tests this hypothesis with respect to the proposed diagnosis of binge eating disorder (BED) in an epidemiological sample of people of Mexican origin in Mexico and the U.S. Data come from the Mexico National Comorbidity Survey, National Comorbidity Survey Replication, and National Latino and Asian American Survey (N = 2268). Diagnoses were assessed with the WMH-CIDI. Six groups were compared: Mexicans with no migrant family members, Mexicans with at least one migrant family member, Mexican return-migrants, Mexican-born migrants in the U.S., and two successive generations of Mexican-Americans in the U.S. The lifetime prevalence of BED was 1.6% in Mexico and 2.2% among Mexican Americans. Compared with Mexicans in families with migrants, risk for BED was higher in US-born Mexican-Americans with two U.S.-born parents (aHR = 2.58, 95% CI 1.12-5.93). This effect was attenuated by 24% (aHR = 1.97, 95% CI 0.84-4.62) with adjustment for prior-onset depressive or anxiety disorder. Adjustment for prior-onset conduct disorder increased the magnitude of association (aHR = 2.75, 95% CI 1.22-6.20). A similar pattern was observed for binge eating. Among respondents reporting binge eating, onset in the U.S. (vs. Mexico) was not associated with prevalence of further eating disorder symptoms. Migration from Mexico to the U.S. is associated with an increased risk for BED that may be partially attributable to non-specific influences on internalizing disorders. Among respondents reporting binge eating in either country, similar levels of further symptoms were endorsed, suggesting some cross-cultural generalizability of criteria. PMID- 22070905 TI - Genetic variants in nuclear-encoded mitochondrial proteins are associated with oxidative stress in obsessive compulsive disorders. AB - Obsessive compulsive disorder is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions. The mutations or polymorphic variants in mitochondrial DNA-encoded genes or nuclear genes result in oxidative stress, which has recently been associated with various psychiatric disorders. In order to understand the association of mitochondrial disorders with oxidative stress in obsessive compulsive disorder, we examined genetic variants of manganese superoxide dismutase and uncouple-2 antioxidant genes and malondialdehyde and glutathione, markers of oxidative stress. The study sample comprised 104 patients with OCD and 110 healthy controls. For manganese superoxide dismutase, the frequencies of CT (Ala/Val) genotype (p < 0.01) in patients were significantly lower than those of controls. In contrast, CC (Ala/Ala) genotype was significantly more frequent in patients than controls (p < 0.05). For uncouple-2 I/D, the frequencies of ID genotype (p < 0.01) and I allele (p < 0.05) were lower in patients as compared with controls. In contrast, DD genotype was more prevalent in patients than controls (p < 0.01). While whole blood glutathione was significantly diminished (p < 0.0001), serum malondialdehyde was significantly elevated in patients compared with controls (p < 0.0001). Malondialdehyde levels were significantly elevated in subjects with DD genotype of UCP-2 I/D (p < 0.05) and CC genotype of manganese superoxide dismutase (p < 0.05) as compared with II or ID and TT or CT genotype, respectively. Malondialdehyde levels in patients carrying CC (p < 0.05) or CT (p < 0.05) genotype were significantly higher than those of carrying TT genotype. In conclusion, CC genotype of manganese superoxide dismutase or DD genotype of UCP-2 might result in mitochondrial disorders by increasing oxidative stress in obsessive compulsive disorders. PMID- 22070906 TI - Perception of health risks of electromagnetic fields by MRI radiographers and airport security officers compared to the general Dutch working population: a cross sectional analysis. AB - BACKGROUND: The amount of exposure to electromagnetic fields (EMF) at work is mainly determined by an individual's occupation and may differ from exposure at home. It is, however, unknown how different occupational groups perceive possible adverse health effects of EMF. METHODS: Three occupational groups, the general Dutch working population (n = 567), airport security officers who work with metal detectors (n = 106), and MRI radiographers who work with MRI (n = 193), were compared on perceived risk of and positive and negative feelings towards EMF in general and of different EMF sources, and health concerns by using analyses of variances. Data were collected via an internet survey. RESULTS: Overall, MRI radiographers had a lower perceived risk, felt less negative, and more positive towards EMF and different sources of EMF than the general working population and the security officers. For security officers, feeling more positive about EMF was not significantly related to perceived risk of EMF in general or EMF of domestic sources. Feeling positive about a source did not generalize to a lower perceived risk, while negative feelings were stronger related to perceived risk. MRI radiographers had fewer health concerns regarding EMF than the other two groups, although they considered it more likely that EMF could cause physical complaints. CONCLUSIONS: These data show that although differences in occupation appear to be reflected in different perceptions of EMF, the level of occupational exposure to EMF as such does not predict the perceived health risk of EMF. PMID- 22070907 TI - Measuring the outcomes of long-term care. AB - How should we measure the value of long-term (social) care? This paper describes a care-related quality of life instrument (ASCOT) and considers aspects of its validity. In particular the aim is to assess whether ASCOT is better suited to measuring the impact of long-term care services than the EQ5D health-related quality of life measure. Long-term care services tend to be more concerned with addressing the day-to-day consequences of long-term conditions. As such, a quality of life measure should not be overly focused on the potential impact of services on personal ability and should instead consider how services directly help people to function in everyday life. Construct validity was judged by assessing the degree to which measured quality of life improvement was consistent with the theorised positive correlation between quality of life and the use of home care services. In a 2008/9 sample of people using care services in England, we found that the impact of service use was significant when measured by ASCOT, but not significant when using EQ5D. The results support our hypothesis that ASCOT has greater construct validity in this case. PMID- 22070908 TI - Understanding socio-economic determinants of childhood mortality: a retrospective analysis in Uganda. AB - BACKGROUND: Teso sub-region of Eastern Uganda had superior indices of childhood survival during the period 1959 to 1969 compared to the national average. We analysed the reasons that could explain this situation with a view of suggesting strategies for reducing childhood mortality. METHODS: We compared the childhood mortalities and their average annual reduction rate (AARR) of Teso sub-region with those of Uganda for the period 1959 to 1969. We also compared indicators of social economic well being (such as livestock per capita and per capita intake of protein/energy). In addition data was compared on other important determinants of child survival such as level of education and rate of urbanisation. FINDINGS: In 1969 the infant mortality rate (IMR) for Teso was 94 per 1000 live births compared to the 120 for Uganda. Between 1959 and 1969 the AARR for IMR for Teso was 4.57% compared to 3% for Uganda. It was interesting that the AARR for Teso was higher than that that of 4.4.% required to achieve millennium development goal number four (MDG4). The rate of urbanisation and the level of education were higher in Uganda compared to Teso during the same period. Teso had a per capita ownership of cattle of 1.12 compared to Uganda's 0.44. Teso sub region had about 3 times the amount of protein and about 2 times the amount of calories compared to Uganda. CONCLUSIONS: We surmise that higher ownership of cattle and growing of high protein and energy foods might have been responsible for better childhood survival in Teso compared to Uganda. PMID- 22070909 TI - The STARR operation with the Contour 30(r) (Transtar(r)) stapler for the treatment of obstructed defecation syndrome associated with rectocele and internal rectal prolapse. PMID- 22070910 TI - Porcine plasma as polyphosphate and caseinate replacer in frankfurters. AB - The aim was to replace polyphosphate and caseinate by porcine blood plasma as functional ingredients in frankfurters. Three trials, each consisting of one control, formulated with caseinate and tripolyphosphate, and one test, formulated with plasma, were carried out in a pilot plant. The frankfurters with plasma were compared to their respective controls by determining the composition, water holding capacity, cooking losses, internal colour, texture, microstructure, sensorial characteristics, and overall acceptance. No significant differences were found in proximate analysis, WHC, and cooking losses. Texture was not affected by the replacement, according to both sensorial and instrumental measurements. Nevertheless, the panellists detected the presence of animal taste and odour in plasma-containing sausages. Despite this, their overall acceptance was scored as 6.3 in a 10 maximum scale, so plasma could be considered as an interesting alternative to produce healthier and cheaper frankfurters. PMID- 22070911 TI - Neoadjuvant chemotherapy prior to surgery in head and neck cancer. PMID- 22070913 TI - IL-1 receptor-associated kinase 3 gene (IRAK3) variants associate with asthma in a replication study in the Spanish population. PMID- 22070914 TI - Reference values and clinical application of magnetic peripheral nerve stimulation in cats. AB - Magnetic stimulation of radial (RN) and sciatic (SN) nerves was performed bilaterally in 40 healthy cats. Reference values for onset latency and peak-to peak amplitude of magnetic motor evoked potentials (MMEPs) were obtained and compared with values of electric motor evoked potentials (EMEPs) in 10/40 cats. Onset latencies and peak-to-peak amplitudes of the MMEPs of three cats with polyneuropathy (PNP) were compared to the reference values. Magnetic motor evoked responses were easily recorded in all normal cats. Significant differences were found in onset latencies between MMEPs and EMEPs, but peak-to-peak amplitudes were equal. The MMEPs of three cats with PNP can be seen as outliers in comparison to the reference values. MMEPs from the RN and SN were easily obtained and reproducible in normal cats. The technique could represent a useful adjunct in the assessment of peripheral nerve disorders. PMID- 22070912 TI - The C11orf30-LRRC32 region is associated with total serum IgE levels in asthmatic patients. PMID- 22070915 TI - Effects of the GnRH antagonist acyline on the testis of the domestic cat (Felis catus). AB - The aim of this study was to describe the effects of a single dose of the gonadotrophin releasing hormone (GnRH) antagonist acyline on testicular characteristics of the domestic cat. Twelve mature cats were orchidectomised unilaterally (right testis) on Day -7 (n=7) or Day 15 (n=5). On Day 0, 330 MUg/kg acyline was administered s.c. to all the animals. Left orchidectomy was carried out on Day 15 (n=2), Day 30 (n=4) and Day 60 (n=6). Sperm were recovered from the epididymis and the testes were evaluated grossly, histologically and immunohistochemically. Significant differences (P<0.05) were found between days for epididymal sperm motility, vigor, abnormal morphology, germinal epithelium height, spermatocytes, spermatids, spermatozoa, lumen and cellular debris. Conversely, no significant differences were found for gross testicular and tubular characteristics, spermatogonia, Sertoli and Leydig cells and intertubular compartments. It was concluded that a single dose of acyline reversibly impaired spermiogenesis, spermatocytogenesis and sperm motility for 2 weeks. PMID- 22070917 TI - Toll-like receptor 3-mediated tumor invasion in head and neck cancer. AB - OBJECTIVES: Chronic inflammation associated with some infectious agents can lead to cancer. The Toll-like receptor (TLR) family is one of the largest and best studied families of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA and is a major effector of the immune response against viral pathogens. MATERIALS AND METHODS: We investigated TLR3 protein expression in 153 oral squamous cell carcinoma (OSCC) specimens using tissue microarray. Furthermore, we used polyinosinic-polycytidylic acid (poly I:C) to stimulate head and neck cancer cells and an inhibitor of endosomal acidification bafilomycin A1 to block the TLR 3 signaling pathway to clarify the role of TLR 3 in OSCC. RESULTS: Cytoplasmic TLR3 staining was observed in the vast majority of OSCC tissues (73.2%). Strong TLR3 expression was significantly correlated with patients whose tumors were poorly differentiated (P=0.028) and with perineural invasion (P=0.023). Three of the four head and neck cell lines tested (Fadu, OC2, and SCC4) expressed TLR3 mRNA, although at various levels. The stimulation of TLR3-expressing OC2 cells with poly I:C caused the phosphorylation of IFN regulatory factor 3 and IkappaB and sequentially induced the secretion of interleukin-6 and chemokine (C-C motif) ligand 5 (CCL5) in a dose- and time dependent manner. Moreover, poly I:C stimulation promoted CCL5-mediated migration in OC2 cells. CONCLUSIONS: In this report, we provide a novel mechanism for tumor invasion and the TLR3-dependent inflammatory response that could have therapeutic implications for OSCC. PMID- 22070918 TI - Proposed clinical classification for oral submucous fibrosis. AB - Oral Submucous Fibrosis (OSMF) is a chronic, progressive, scarring disease, that predominantly affects people of South Asia and South-East Asia, where chewing of arecanut and its commercial preparation is high. Presence of fibrous bands is the main characteristic feature of OSMF. Based on clinical and/or histopathological features of OSMF, various classifications have been put forth till date. But the advantages and drawbacks of these classification supersedes each other, leading to perplexity. Our various studies and clinical experience in the field of OSMF have initiated us to propose/introduce the new clinical classification which could assist the clinician in the categorization of this potentially malignant disorder according to its biological behaviour and hence its subsequent medical and surgical management. PMID- 22070919 TI - Priming does not enhance the efficacy of 1 Hertz repetitive transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study. AB - BACKGROUND: Low-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the left temporoparietal area (TP) has been investigated as a treatment method for auditory verbal hallucinations (AVH) yielding inconsistent results. In vitro studies have indicated that the effects of low-frequency rTMS can be enhanced by a brief pretreatment phase consisting of high-frequency rTMS (i.e., priming rTMS). OBJECTIVE: The aim of this single-blind, randomized controlled study was to investigate whether the effects of rTMS on AVH can be enhanced with priming rTMS. METHODS: Twenty-three patients with medication resistant AVH were randomized over two groups: one receiving low-frequency rTMS preceded by 5 minutes of 6 Hertz rTMS; and another receiving low-frequency rTMS without priming. Both treatments were directed at the left TP. The total duration of stimulation was equal in the two groups, namely, 15 sessions of 20 minutes each. The severity of AVH and other psychotic features were measured with the aid of the Auditory Hallucination Rating Scale (AHRS), the Positive and Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scales (PSYRATS). RESULTS: The severity of AVH and other psychotic symptoms in the group with priming was not significantly lower after 3 weeks of treatment in comparison to baseline. The group treated with standard rTMS showed a trend toward improvement after 3 weeks of treatment. No significant differences were observed on any of the rating scales between the group with and without priming. CONCLUSIONS: This study does not provide evidence that priming rTMS is an effective treatment for AVH. PMID- 22070916 TI - The biology of head and neck cancer stem cells. AB - Emerging evidence indicates that a small population of cancer cells is highly tumorigenic, endowed with self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the "drivers" of the tumorigenic process in some tumor types, and have been named cancer stem cells. Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. Cancer stem cells have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. The head and neck cancer stem cells reside primarily in perivascular niches in the invasive front where endothelial-cell initiated events contribute to their survival and function. In this review, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells to head and neck tumor progression. PMID- 22070920 TI - SOX2-RNAi attenuates S-phase entry and induces RhoA-dependent switch to protease independent amoeboid migration in human glioma cells. AB - BACKGROUND: SOX2, a high mobility group (HMG)-box containing transcription factor, is a key regulator during development of the nervous system and a persistent marker of neural stem cells. Recent studies suggested a role of SOX2 in tumor progression. In our previous work we detected SOX2 in glioma cells and glioblastoma specimens. Herein, we aim to explore the role of SOX2 for glioma malignancy in particular its role in cell proliferation and migration. METHODS: Retroviral shRNA-vectors were utilized to stably knockdown SOX2 in U343-MG and U373-MG cells. The resulting phenotype was investigated by Western blot, migration/invasion assays, RhoA G-LISA, time lapse video imaging, and orthotopic xenograft experiments. RESULTS: SOX2 depletion results in pleiotropic effects including attenuated cell proliferation caused by decreased levels of cyclinD1. Also an increased TCF/LEF-signaling and concomitant decrease in Oct4 and Nestin expression was noted. Furthermore, down-regulation of focal adhesion kinase (FAK) signaling and of downstream proteins such as HEF1/NEDD9, matrix metalloproteinases pro-MMP-1 and -2 impaired invasive proteolysis-dependent migration. Yet, cells with knockdown of SOX2 switched to a RhoA-dependent amoeboid-like migration mode which could be blocked by the ROCK inhibitor Y27632 downstream of RhoA-signaling. Orthotopic xenograft experiments revealed a higher tumorigenicity of U343-MG glioma cells transduced with shRNA targeting SOX2 which was characterized by increased dissemination of glioma cells. CONCLUSION: Our findings suggest that SOX2 plays a role in the maintenance of a less differentiated glioma cell phenotype. In addition, the results indicate a critical role of SOX2 in adhesion and migration of malignant gliomas. PMID- 22070921 TI - ECM roles in the function of metabolic tissues. AB - All metazoan cells produce and/or interact with tissue-specific extracellular matrices (ECMs). Such ECMs play important structural roles not only in connective tissues, but in all tissues in which they provide support and anchorage for cells. However, in addition to such structural roles it has become increasingly clear that the tissue-specific microenvironments formed by the ECM play instructional roles that inform the proper phenotypes and functional behaviors of specialized cell types, and recent in vivo and in vitro studies suggest that ECM components also affect metabolic function. This review summarizes data that provide insights into the roles of the ECM in informing the proper development and functioning of highly specialized cells of metabolic tissues, such as adipocytes and islet beta cells. PMID- 22070922 TI - Frequency of KRAS, BRAF, and PIK3CA mutations in advanced colorectal cancers: Comparison of peptide nucleic acid-mediated PCR clamping and direct sequencing in formalin-fixed, paraffin-embedded tissue. AB - KRAS, BRAF, and PIK3CA mutation testing before administration of anti-epidermal growth factor receptor therapy of metastatic colorectal cancer (CRC) has become important. However, considerable uncertainty exists regarding which detection method can be applied in a reproducible, sensitive, and simple manner in the routine diagnostic setting. We compared the detection rates of KRAS, BRAF, and PIK3CA mutations in 92 routine formalin-fixed, paraffin-embedded CRC specimens by 2 discrete methods: direct sequencing and peptide nucleic acid (PNA)-mediated PCR. The detection rates for KRAS, BRAF, and PIK3CA mutations by direct sequencing were 20.7%, 3.3%, and 1.1%, respectively. PNA-mediated PCR clamping significantly increased the percentages of KRAS, BRAF, and PIK3CA mutations by up to 7.6%, 1.2%, and 5.4%, respectively, compared to the detection rate of regular PCR followed by direct sequencing (p=0.039, p=0.250, and p=0.031, respectively). The tumor volume of discordant cases was not significantly different from concordant cases (56.2+/-28.7% vs. 67.6+/-17.9%, p=0.41), which implies that there is a minor population of mutant alleles in the heterogeneous tumor population. The PNA-mediated PCR clamping method is highly sensitive and is efficiently applicable to the detection of KRAS, BRAF, and PIK3CA mutations in a clinical setting. PMID- 22070923 TI - Cognition and lobar morphology in full mutation boys with fragile X syndrome. AB - The aims of the present study are twofold: (1) to examine cortical morphology (CM) associated with alterations in cognition in fragile X syndrome (FXS); (2) to characterize the CM profile of FXS versus FXS with an autism diagnosis (FXS+Aut) as a preliminary attempt to further elucidate the behavioral distinctions between the two sub-groups. We used anatomical magnetic resonance imaging surface-based morphometry in 21 male children (FXS N=11 and age [2.27-13.3] matched controls [C] N=10). We found (1) increased whole hemispheric and lobar cortical volume, cortical thickness and cortical complexity bilaterally, yet insignificant changes in hemispheric surface area and gyrification index in FXS compared to C; (2) linear regression analyses revealed significant negative correlations between CM and cognition; (3) significant CM differences between FXS and FXS+Aut associated with their distinctive behavioral phenotypes. These findings are critical in understanding the neuropathophysiology of one of the most common intellectual deficiency syndromes associated with altered cognition as they provide human in vivo information about genetic control of CM and cognition. PMID- 22070924 TI - The interaction between surface color and color knowledge: behavioral and electrophysiological evidence. AB - In this study, we used event-related potentials (ERPs) to evaluate the contribution of surface color and color knowledge information in object identification. We constructed two color-object verification tasks - a surface and a knowledge verification task - using high color diagnostic objects; both typical and atypical color versions of the same object were presented. Continuous electroencephalogram was recorded from 26 subjects. A cluster randomization procedure was used to explore the differences between typical and atypical color objects in each task. In the color knowledge task, we found two significant clusters that were consistent with the N350 and late positive complex (LPC) effects. Atypical color objects elicited more negative ERPs compared to typical color objects. The color effect found in the N350 time window suggests that surface color is an important cue that facilitates the selection of a stored object representation from long-term memory. Moreover, the observed LPC effect suggests that surface color activates associated semantic knowledge about the object, including color knowledge representations. We did not find any significant differences between typical and atypical color objects in the surface color verification task, which indicates that there is little contribution of color knowledge to resolve the surface color verification. Our main results suggest that surface color is an important visual cue that triggers color knowledge, thereby facilitating object identification. PMID- 22070925 TI - Vancouver simplified grading system with computed tomographic angiography for blunt aortic injury. AB - OBJECTIVE: Delineation of blunt aortic injury by computed tomographic angiography guides management of this potentially fatal injury. Two existing grading systems are problematic to apply and not linked to outcomes. A simplified computed tomographic angiography-based grading system, linked to clinical outcomes, was developed, and feasibility and reliability were evaluated. METHODS: Retrospective review was performed of all blunt aortic injury cases presenting to a single provincial quaternary referral center designated for blunt aortic injury management between 2001 and 2009. Management, associated injuries, hospital survival, and cause of death were determined. Initial computed tomographic angiography was reviewed, and injuries were graded according to the new Vancouver simplified grading system by 2 study authors. Three additional trauma radiologists then graded the aortic injuries with the 2 existing systems and the simplified system. Interrater reliability was determined. RESULTS: Forty-eight patients were identified. Two had minimal aortic injury (grade I), 7 had an intimal flap larger than 1 cm (grade II), 32 had traumatic pseudoaneurysm (grade III), 6 had active contrast extravasation (grade IV), and 1 could not be rated. Survivals were 100%, 90%, and 33% for grades I and II, III, and IV, respectively. Of grade III injuries, 14% were medically managed, 68% repaired endovascularly, and 18% repaired with open surgery. Interrater correlation was best with the simplified score, with only 0.5% of cases unable to be classified. CONCLUSIONS: The Vancouver simplified blunt aortic injury grading system is easy to use and correlates with clinical outcomes. Prospective external validation is required. PMID- 22070927 TI - Endoscopic fundoplication for the treatment of gastroesophageal reflux disease: initial experience. AB - OBJECTIVE: Transoral incisionless fundoplication (TIF) is a promising approach for gastroesophageal reflux disease (GERD) that may decrease morbidity compared with conventional antireflux procedures. We report our initial experience with this minimally invasive approach. METHODS: Over a 24-month period, 46 patients (mean age, 49 years; 50% female) underwent 48 TIF procedures. All procedures were performed under general anesthesia. Two surgeons participated in all cases; one served as the endoscopist, and the other performed the partial fundoplication. Heartburn severity was measured using the GERD health-related quality of life (GERD-HRQL) instrument (best score = 0, worst score = 45), which includes an additional question assessing overall satisfaction. RESULTS: Preoperatively, 33 (72%) of 46 patients had small (<3 cm) hiatal hernias, and none had undergone any previous antireflux procedures. Preoperative workup included manometry and barium esophagogram, with pH testing reserved for patients with atypical symptoms or typical symptoms and a lack of response to proton-pump inhibitors. The mean procedure time was 83 minutes (range, 36-180 minutes). The mean procedure time decreased after the first 5 cases from 122 to 78 minutes (P = .001). Mean length of stay was 1.3 days. One patient was readmitted with aspiration pneumonia. Three patients had minor complications (1 had minor bleeding from a suture site and 2 had urinary retention). There were no perioperative deaths. Mean follow-up was 140 days. The mean GERD-HRQL scores improved significantly (23 vs 7; P < .001). There were 22 patients with follow-up greater than 90 days (mean follow-up, 240 days). GERD-HRQL scores remained significantly improved for these patients (23 vs 8; P = .001). Four patients from the entire group (8.6%) had no improvement, in 3 instances due to breakdown of the wrap. Two patients were treated with repeat endoscopic fundoplication and 1 was treated with laparoscopic Nissen fundoplication, and all had a significant improvement in symptoms after reoperation. CONCLUSIONS: TIF is effective at short-term follow-up and safe for patients with GERD. However, long-term follow-up and randomized trials are required to assess the efficacy and durability of this approach compared with conventional surgical repair. PMID- 22070928 TI - Low-dose spinal anesthesia with hyperbaric bupivacaine with intrathecal fentanyl for operative hysteroscopy: a case series study. AB - STUDY OBJECTIVE: To estimate the efficacy and tolerability of low dose spinal anesthesia during operative hysteroscopy in a group of patients with high surgical risks. DESIGN: Case series study (Canadian Task Force Classification II 2). SETTING: Tertiary centers for women health care. PATIENTS: A total of 47 women affected by endometrial polyps (n = 32), myomas (n = 8), and abnormal uterine bleeding (n = 7) scheduled for inpatient operative hysteroscopy. INTERVENTIONS: Transvaginal ultrasonography; office diagnostic hysteroscopy; preoperative evaluation of American Society of Anesthesiologist (ASA) classification; inpatient operative hysteroscopy; low-dose spinal anesthesia with hyperbaric bupivacaine; compilation of a questionnaire. MAIN OUTCOME MEASURES: Practicability and patients' subjective experiences with spinal anesthesia; duration of cervical dilation and for operative hysteroscopy; infusion volume needed; incidence of surgical complications. RESULTS: Resectoscopy was performed in all patients, with the exception of 1 woman (2.1%) in which spinal anesthesia was unsuccessful. No statistically significant differences were noted among groups in terms of intra- and peri-operative findings. Sensory block induced by spinal anesthesia was suitable for surgery in all patients, and side effects occurred far less frequently than mentioned in the literature. Data reported in the questionnaire revealed that 93.5% of women would choose a spinal anesthesia again for a potential operative hysteroscopy in the future, since for 89.1% of them long lasting anesthesia is of relevance. CONCLUSIONS: Low-dose spinal anesthesia is a feasible technique in the inpatient setting for operative hysteroscopy in women with high surgical risks. PMID- 22070929 TI - Myomectomy decreases abnormal uterine peristalsis and increases pregnancy rate. AB - BACKGROUND: The relationship between fibroids and infertility remains a critical and unresolved question. During the implantation phase, it is known that uterine peristalsis is dramatically reduced, which is thought to facilitate implantation of the embryo to the endometrium. In the previous study, using a cine MRI mode, we found that less than half of the patients with intramural fibroids exhibited abnormal uterine peristalsis during the mid-luteal phase. In the present study, we further investigated whether myomectomy for patients in the high peristalsis group is a constructive method to normalize uterine peristalsis. METHODS: The frequency of junctional zone movement was evaluated using a cine MRI mode during the mid-luteal phase. Fifteen infertility patients, who had intramural myomas and exhibited abnormal uterine peristalsis (>=2 times/3 min) in their first MRI, underwent myomectomy and a second MRI. After receiving the second MRI, patients underwent infertility treatment for at least 8 months, and pregnancy rate was evaluated prospectively. RESULTS: Among 15 patients, the frequency of uterine peristalsis was normalized (0 or 1 time/3 min) in 14 patients. Following myomectomy and second MRI test, 6 of the 15 patients achieved pregnancy (n = 15, pregnancy rate: 40%). CONCLUSIONS: The presence of uterine fibroids might induce abnormal uterine peristalsis in some patients, leading to infertility, and myomectomy may improve fertility in these patients. PMID- 22070930 TI - Brain tumor eradication and prolonged survival from intratumoral conversion of 5 fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector. AB - Patients with the most common and aggressive form of high-grade glioma, glioblastoma multiforme, have poor prognosis and few treatment options. In 2 immunocompetent mouse brain tumor models (CT26-BALB/c and Tu-2449-B6C3F1), we showed that a nonlytic retroviral replicating vector (Toca 511) stably delivers an optimized cytosine deaminase prodrug activating gene to the tumor lesion and leads to long-term survival after treatment with 5-fluorocytosine (5-FC). Survival benefit is dose dependent for both vector and 5-FC, and as few as 4 cycles of 5-FC dosing after Toca 511 therapy provides significant survival advantage. In the virally permissive CT26-BALB/c model, spread of Toca 511 to other tissues, particularly lymphoid tissues, is detectable by polymerase chain reaction (PCR) over a wide range of levels. In the Tu-2449-B6C3F1 model, Toca 511 PCR signal in nontumor tissues is much lower, spread is not always observed, and when observed, is mainly detected in lymphoid tissues at low levels. The difference in vector genome spread correlates with a more effective antiviral restriction element, APOBEC3, present in the B6C3F1 mice. Despite these differences, neither strain showed signs of treatment-related toxicity. These data support the concept that, in immunocompetent animals, a replicating retroviral vector carrying a prodrug activating gene (Toca 511) can spread through a tumor mass, leading to selective elimination of the tumor after prodrug administration, without local or systemic pathology. This concept is under investigation in an ongoing phase I/II clinical trial of Toca 511 in combination with 5-FC in patients with recurrent high-grade glioma (www.clinicaltrials.gov NCT01156584). PMID- 22070931 TI - Absence of the lectin activation pathway of complement does not increase susceptibility to Pseudomonas aeruginosa infections. AB - Pseudomonas aeruginosa remains one of the major clinical pathogens that burden immuno-compromised patients and patients with cystic fibrosis. The present study aimed to define the role of the lectin pathway of complement in the immune defence against P. aeruginosa in a mouse model of invasive pneumonia. Using in vitro assays specific for each of the three complement pathways, we demonstrate that some strains of P. aeruginosa bind lectin pathway recognition sub-components and initiate complement activation in a lectin pathway-specific mode. All of the tested strains activated complement via classical and alternative pathways. We assessed the importance of lectin pathway activation in fighting P. aeruginosa infections by testing a lectin pathway activating strain in a mouse model of intra-nasal infection. MASP-2 (mannan binding lectin associated serine protease 2) deficient mice, which have no lectin pathway activity, had no significant survival disadvantage compared to wild type littermates (72.7% and 81.8% survival, respectively, p=0.48). Likewise, no difference in opsonising activity was seen between MASP-2 sufficient and MASP-2 deficient mouse sera. Moreover, cytokine expression profiles in the lungs of WT mice and MASP-2-/- mice were similar throughout the course of P. aeruginosa infection. We conclude that the lectin pathway does not play an essential role in fighting P. aeruginosa infection in mice. PMID- 22070932 TI - Smurf2 regulates IL17RB by proteasomal degradation of its novel binding partner DAZAP2. AB - IL17RB is the receptor for IL17E, the only member of IL17 family promoting Th2 reactions. The mechanism of IL17BR regulation is poorly understood. We previously demonstrated that expression of IL17RB is induced on human macrophages by IL4 and enhanced by TGFbeta. In the present study we investigated the immediate signaling targets of IL17RB. Using Yeast Two Hybrid screening we identified DAZAP2 as a binding partner of IL17RB. We established that 2 SH2-binding domains of DAZAP2 are essential for its binding to IL17RB. Deletion of these domains or substitution of tyrosines to alanines abrogates the binding. In IL17RB DAZAP2 binding domain was mapped to the region between aa 329 and 347 within its cytoplasmic part. Confocal microscopy revealed that in primary human macrophages that do not express IL17RB DAZAP2 is predominantly localized in the nucleus, while in IL17RB positive macrophages a portion of DAZAP2 is visualized in the cytoplasm. Stimulation of IL17RB with its ligand IL17E induces accumulation of DAZAP2 in the cytoplasm. Further we established that DAZAP2 interacts with Smurf2 an E3 ubiquitin ligase which induces proteasome-dependent degradation of the protein. In summary we established a new mechanism of IL17RB regulation-Smurf2 dependent degradation of its adaptor protein DAZAP2. PMID- 22070933 TI - Cell therapy for refractory angina: time for more ACTion. AB - Chronic ischemic heart disease is a major cause of patient morbidity and healthcare expenditure. The development of therapies aimed to enhance angiogenesis is targeted for patients with severe ischemic symptoms that persist despite optimized medical therapy and in whom coronary revascularization procedures are no longer feasible or helpful. Several different stem, progenitor and mature cell types have so far shown potential to improve myocardial perfusion and vascularity after transplantation in preclinical models of ischemia. However, human studies of cell-based transfer have heavily focused on preventing cardiac remodeling and dysfunction in the setting of myocardial infarction, while relatively few have addressed the use of cells to treat patients suffering from chronic debilitating angina. To this end, the recent ACT34-CMI trial represents a seminal milestone in the clinical evolution of cell therapy for chronic ischemic heart disease. In this phase II placebo-controlled study, myocardial injection of autologous peripheral blood-derived CD34+ progenitor cells was shown to confer considerable benefit for symptom frequency and exercise tolerance in patients with refractory, class III and IV angina. The present commentary reviews the key lessons from this unique trial and considers its contributions in moving the field of cell-based cardiovascular research forward. PMID- 22070934 TI - Pattern of childhood burn injuries and their management outcome at Bugando Medical Centre in Northwestern Tanzania. AB - BACKGROUND: Burn injuries constitute a major public health problem and are the leading cause of childhood morbidity and mortality worldwide. There is paucity of published data on childhood burn injuries in Tanzania, particularly the study area. This study was conducted to describe the pattern of childhood burn injuries in our local setting and to evaluate their management outcome. METHODS: A cross sectional study was conducted at Bugando Medical Centre (in Northwestern Tanzania) over a 3-year period from January 2008 to December 2010. Data was collected using a pre-tested coded questionnaire and statistical analyses performed using SPSS software version 15.0. RESULTS: A total of 342 burned children were studied. Males were mainly affected. Children aged = 2 were the majority accounting for 45.9% of cases. Intentional burn injuries due to child abuse were reported in 2.9% of cases. Scald was the most common type of burns (56.1%). The trunk was the most commonly involved body region (57.3%). Majority of patients (48.0%) sustained superficial burns. Eight (2.3%) patients were HIV positive. Most patients (89.8%) presented to the hospital later than 24 h. The rate of burn wound infection on admission and on 10th day were 32.4% and 39.8% respectively.Staphylococcus aureus were more common on admission wound swabs, with Pseudomonas aeruginosa becoming more evident after 10th day. MRSA was detected in 19.2% of Staphylococcus aureus. Conservative treatment was performed in 87.1% of cases. Surgical treatment mainly skin grafting (65.9%) was performed in 44 (12.9%) of patients. The overall average of the length of hospital stay (LOS) was 22.12 +/- 16.62 days. Mortality rate was 11.7%. Using multivariate logistic regression analysis; age of the patient, type of burn, delayed presentation, clothing ignition, %TBSA and severity of burn were found to be significantly associated with LOS (P < 0.001), whereas mortality rate was found to be independently and significantly related to the age of the patient, type of burn, HIV positive with stigmata of AIDS, CD4 count, inhalation injury, %TBSA and severity of burn (P < 0.001). CONCLUSION: Childhood burn injuries still remain a menace in our environment with virtually unacceptable high morbidity and mortality. There is need for critical appraisal of the preventive measures and management principles currently being practiced. PMID- 22070935 TI - Age differential between outcomes of carotid angioplasty and stent placement and carotid endarterectomy in general practice. AB - BACKGROUND: Data derived from prospective randomized clinical trials suggest differential comparative benefit between carotid angioplasty and stent (CAS) placement and carotid endarterectomy (CEA) in various age strata. We sought to investigate the impact of age on outcomes of CAS and CEA in general practice. METHODS: We analyzed the data from the Nationwide Inpatient Sample (NIS), which is representative of all admissions in the United States from 2005 to 2008. The primary end point was occurrence of stroke, cardiac complications, or death during the postprocedural period. Outcomes of interest were compared between patients aged >=70 years and <70 years, undergoing CEA and CAS. Multivariate logistic regression was performed to determine the effect of age on occurrence of postoperative stroke, cardiac complications, or death. Covariates included in the logistic regression were patient's age, gender, comorbid conditions, including hypertension, diabetes mellitus (DM), chronic lung disease, coronary artery disease (CAD), congestive heart failure (CHF), and renal failure; symptom status (symptomatic vs asymptomatic status), and hospital characteristics. RESULTS: Of the total 495,331 estimated patients who received treatment for CAD during the study period, 88% underwent CEA and the remaining 12% underwent CAS. Of the total procedures, 41% of the procedures were performed in patients aged <70 years compared to the remaining 59% that were performed among patients aged >=70 years. For patients undergoing CAS, age >=70 years was an important predictor of postoperative stroke (P = .0025; odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.5) and cardiac complications postprocedure (P = .045; OR, 1.3; 95% CI, 1.0-1.6). For patients undergoing CEA, age >=70 years was associated with higher cardiac complications (P < .001; OR, 1.5; 95% CI, 1.3-1.7) and higher postoperative mortality risk (P = .0008; OR, 1.4; 95% CI, 1.1-1.8) compared to patients aged <70 years. The increased risk of composite end point (postoperative stroke/cardiac complications/mortality) among patients aged >=70 years was a significant factor for patients undergoing either CAS or CEA (OR of 1.3 for both procedures). CONCLUSION: Our analysis suggests that most CAS and CEAs are performed in patients aged >=70 years in general practice, and higher rates of postoperative complications are observed among these patients regardless of procedure choice. PMID- 22070937 TI - Factors affecting the patency of arteriovenous fistulas for dialysis access. AB - BACKGROUND: The autologous arteriovenous fistula (AVF) is the accepted gold standard mode of repeated vascular access for hemodialysis in terms of access longevity, patient morbidity, and health care costs. This review assesses the current evidence supporting the role of various patient and surgeon factors on AVF patency. METHODS: The literature was searched to identify the current evidence available for patient characteristics, methods of AVF planning, and anatomic factors that may affect patency outcomes after AVF formation. The use of adjuvant medications, surgical techniques, and policies for AVF maintenance are discussed in relation to AVF patency. RESULTS: Current literature supports patient factors, such as increasing age, presence of diabetes, smoking, peripheral vascular disease, predialysis hypotension, and vessel characteristics, as directly influencing AVF patency. Vessels of small caliber (<2 mm) or demonstrating reduced distensibility are unlikely to create a functional AVF. Current evidence does not support altered patency due to sex or raised body mass index (<35 kg/m(2)). Factors such as early referral for AVF, preoperative ultrasound vessel mapping, use of vascular staples, and intraoperative flow measurements affected AVF patency, but the use of medical adjuvant therapies did not. Programs of surveillance and various needling techniques to maintain patency are not supported by current evidence. Novel techniques of infrared radiotherapy and topical glyceryl trinitrate are possible future strategies to increase AVF patency rates. The limitations of available evidence include a lack of large, randomized controlled trials and meta-analysis data to support current practice. CONCLUSIONS: There is a complex interaction of factors that may affect the patency of an individual AVF. These need to be carefully considered when selecting surgical site or technique, adjuvant treatments, and follow-up protocols for AVFs. PMID- 22070936 TI - Carotid endarterectomy in the acute phase of stroke-in-evolution is safe and effective in selected patients. AB - OBJECTIVE: This study documented with independent neurologic assessment the 30 day and 90-day outcomes in selected patients with severe internal carotid artery (ICA) stenosis who underwent carotid endarterectomy (CEA) in the acute phase of stroke-in-evolution (SIE). METHODS: From January 2003 to December 2010, data from patients who had surgery <=2 weeks of an SIE with high-grade carotid stenosis were extracted from two prospectively collected databases. Clinical assessment was by the vascular neurologist using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale score. All patients had computed tomography or magnetic resonance brain imaging <=3 hours of stroke onset. Those eligible received thrombolysis. Duplex ultrasound imaging was initially used for the diagnosis of severe (>=60%) ICA stenosis, and further assessment was by magnetic resonance or computed tomography angiography, or both. Perioperative medical treatment and operative techniques were standardized. Stroke, death, major cardiac events, and functional outcome were analyzed. RESULTS: Twenty-seven patients underwent carotid revascularization in the acute phase of SIE. Fluctuating or progressive neurologic deficit was the presenting pattern in 20 patients and occurred after otherwise successful thrombolytic therapy in the remaining 7 (26%). Median NIHSS score at admission was 8. Median delay to surgery from the index event was 6 days. The mean degree of ICA stenosis was 87%. All patients received antiplatelet and statin therapy during the intervening period. Procedures were conventional CEA with patch angioplasty (polytetrafluoroethylene) in 26 patients (96.3%) and redo interposition bypass grafting in 1 patient. CEA was done under local anesthesia in 23 patients (85.2%), with selective shunting in 3 (13.0%), and under general anesthesia, with systematic shunting in 4. At discharge and at 1 and 3 months, no recurrent stroke or death, and one nonfatal myocardial infarction occurred in this series, with a 100% complete follow-up. At 3 months, all patients had a favorable functional outcome defined as a modified Rankin Scale score of <=2. CONCLUSIONS: This short series demonstrates that CEA in the acute phase of SIE with strict selection criteria and close blood pressure monitoring is safe, even after recent thrombolytic therapy, and is effective in functional outcome at 3 months. Larger series of patients are required to confirm the safety and efficacy of this management. PMID- 22070938 TI - A novel approach using pulmonary artery catheter-directed rapid right ventricular pacing to facilitate precise deployment of endografts in the thoracic aorta. AB - OBJECTIVE: Controlled hypotension is critical for precise deployment of endografts in the thoracic aorta and for safe balloon dilation after deployment. We describe a novel approach to rapid right ventricular pacing using a pulmonary artery catheter (PAC) that is placed during the procedure for hemodynamic monitoring. METHODS: The study included 27 patients (20 men and seven women), with a mean age of 74 years, who underwent endograft placement in the thoracic aorta with PAC-directed rapid right ventricular pacing. Hemodynamic parameters, accuracy of deployment, complications related to rapid right ventricular pacing and PAC placement, presence of endoleaks, and postoperative complications were evaluated. RESULTS: PAC-directed rapid right ventricular pacing was performed during endograft deployment and balloon dilation after deployment without technical difficulty. Each patient underwent a median of two pacing episodes (range, 1-4). The length of each pacing episode was a mean of 11 seconds (range, 8-14 seconds). Mean pacing rate was 170 +/- 15 beats/min, which achieved an average mean arterial pressure (MAP) of 42 +/- 8 mm Hg. After pacing cessation, the recovery time of MAP to prepacing levels was <5 seconds (mean, 2 seconds) in all but one patient. All endografts were precisely deployed at a mean of 2 mm from the intended placement site, and there was no unintentional branch vessel coverage. One patient with severe valvular heart disease died. There were nine endoleaks, one postoperative stroke (4%), and one access wound hematoma (4%). CONCLUSIONS: PAC-directed rapid right ventricular pacing is an effective method of inducing hypotension, enabling precise thoracic endograft deployment and safe balloon dilation after deployment. However, despite these advantages, the technique may be contraindicated in patients with severe valvular or ischemic heart disease. PMID- 22070939 TI - Migration of central lines from the superior vena cava to the azygous vein. AB - AIM: To report 11 cases of central venous access catheters migrating from the superior vena cava to the azygos vein in order to raise radiologists' awareness of this possibility. MATERIALS AND METHODS: This is a retrospective review of the clinical history and imaging of 11 patients whose central line migrated from the superior vena cava to the azygos vein. The time course of migration, access route of the catheters, outcome, and depth of placement in the superior vena cava were evaluated. RESULTS: All of these catheters were placed from the left; six through the subclavian vein, four as PICC lines, and one from the left internal jugular vein. Seven of the catheters were originally positioned in the superior vena cava. Four of the catheters were originally positioned in the azygos vein and were repositioned into the superior vena cava at the time of placement. The time to migration ranged from 2 to 126 days, average 43 days. In three cases, the migration was not reported at the first opportunity, resulting in a delay in diagnosis ranging from 10 to 27 days. All but one of the catheters extended at least 3.5 cm (range 1.8-7 cm) below the top of the right mainstem bronchus when in the superior vena cava. CONCLUSION: Risk factors for migration into the azygos vein include placement from a left-sided approach and original positioning in the azygos vein with correction at placement. The depth of placement in the superior vena cava was not a protective factor. It is important to recognize migration because of the elevated risk of complications when central lines are placed in the azygos vein. PMID- 22070940 TI - Pulmonary blood volume imaging with dual-energy computed tomography: spectrum of findings. AB - Dual-energy (DE) pulmonary blood volume (PBV) computed tomography (CT) has recently become available on clinical CT systems. The underlying physical principle of DECT is the fact that the photoelectric effect is strongly dependent on the CT energies resulting in different degrees of x-ray attenuation for different materials at different energy levels. DECT thus enables the characterization and quantification of iodine within tissues via imaging at different x-ray energies and analysis of attenuation differences. Technical approaches to DECT include dual-source scanners acquiring two scans with different energy levels simultaneously, and single-source CT scanners using sandwich detectors or rapid voltage switching. DE PBV CT enables the creation of iodine maps of the pulmonary parenchyma. Experience to date shows that these studies can provide additional physiological information in patients with acute or chronic pulmonary embolism beyond the pure morphological assessment a standard CT pulmonary angiography (CTPA) provides. It appears also to be promising for the evaluation of patients with obstructive airways disease. This article reviews the physics and technical aspects of DE PBV CT as well as the appearance of normal and abnormal lung tissue on these studies. Special consideration is given to pitfalls and artefacts. PMID- 22070941 TI - Congenital anomalies of the inferior vena cava. AB - Congenital anomalies of the inferior vena cava (IVC) and its tributaries are increasingly recognized in asymptomatic patients due to the more frequent use of cross-sectional imaging and computed tomography (CT) in particular. IVC development is a complex process involving formation of anastomoses between three pairs of embryonic veins in the 4th to 8th week of gestation. Various permutations occur in the basic venous plan of the abdomen and pelvis resulting in variants such as isolated left IVC, double IVC, and retroaortic left renal vein. The majority of these anomalies are asymptomatic but occasionally present clinically with thromboembolic complications. However, awareness of their existence is important to avoid important diagnostic pitfalls and in preoperative surgical and interventional radiological planning. PMID- 22070943 TI - CT of the adrenal: not just distinguishing non-adenoma versus adenoma. PMID- 22070944 TI - An observational study to evaluate the performance of units using two radiographers to read screening mammograms. AB - AIM: To examine the performance of screening units in which a proportion of mammograms were double read using "non-discordant radiographer only (double) reading" (NDROR). MATERIALS AND METHODS: NDROR was used by seven pilot units between 2006 and 2009, and six further units in 2009 only. There were 51 comparison units. Screening performance outcome measures were calculated, and logistic regression was used to compare performance between the pilot and comparison units. RESULTS: Phase 1 pilot units read between on average 15 and 48% of mammograms per year using NDROR between 2006 and 2009 (median, 33%) and in 2009, phase 2 pilot units used NDROR to read between 4 and 77% of mammograms (median, 34%). The results showed an increase in recall rates in the phase 1 pilot units relative to the comparison units at both prevalent and incident screens (adjusted OR 1.09, 95% CI 1.05, 1.14; and adjusted OR 1.10, 95% CI 1.07, 1.14, respectively). There were also increases in the phase 2 pilot units relative to the comparison units; adjusted OR 1.08 (95% 1.00, 1.17) at prevalent screens, and adjusted OR 1.07 (95% CI 1.02, 1.14) at incident screens. There was no evidence to suggest a difference in cancer-detection rates between the pilot units and the comparison units. CONCLUSIONS: Evidence from the present study suggests that recall rates may increase as a result of units using radiographers to double read a proportion of their mammograms. However, there is little evidence to suggest that NDROR, as practiced by the pilot units in the present study, is likely to have major impacts on performance in the UK National Health Service Breast Screening Programme (NHSBSP), particularly if it is fully supported and closely monitored (particularly recall rates). PMID- 22070946 TI - Endovascular repair of spontaneous isolated dissection of the superior mesenteric artery. AB - AIM: To present our experience of the clinical management of spontaneous isolated dissection of superior mesenteric artery (SIDSMA) and analyse the clinical features, imaging findings, and treatment outcomes. MATERIALS AND METHODS: In this retrospective study, eight consecutive patients with symptomatic SIDSMA were treated in Chang Gung Memorial Hospital between April 2007 and April 2010; among these patients, six underwent endovascular stent placement. The clinical manifestations, imaging findings, endovascular stent placement outcome, and follow-up results of the patients were retrospectively analysed. RESULTS: Eight patients were diagnosed with SIDSMA by contrast-enhanced computer tomography. One patient died due to comorbidity before angiography. Six patients underwent percutaneous endovascular stent placement in the superior mesenteric artery (SMA): four patients with bare stents and two with stent grafts. Because it was not appropriate to perform stent implantation in the remaining patient, he received only conservative treatment. All seven patients had an uneventful recovery and the follow-up period was 16 month, ranging from 1 to 35 months. CONCLUSION: For patients with symptomatic SIDSMA, endovascular repair is a feasible treatment choice with a high success rate and good clinical outcome. PMID- 22070947 TI - Bovine aortic arch: a novel association with thoracic aortic dilation. AB - AIM: To investigate whether there is a link between bovine arch and thoracic aortic aneurysm. MATERIALS AND METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) images of the thorax of 191 patients with dilated thoracic aortas and 391 consecutive, unselected patients as controls were retrospectively reviewed. Bovine arch was considered present if either a shared origin of the left common carotid and innominate arteries or an origin of the left common carotid from the innominate artery was identified. A chi-square test was used to evaluate the significance of differences between subgroups. RESULTS: A trend towards increased prevalence of bovine arch was seen in patients with dilated aortas (26.2%) compared to controls (20.5%, p=0.12). The association was statistically significant in patients over 70 years old (31.9%, p=0.019) and when dilation involved the aortic arch (47.6%, p=0.003). CONCLUSIONS: An association between bovine arch and aortic dilation is seen in older patients, and when dilation involves the aortic arch. Bovine arch should be considered a potential risk factor for thoracic aortic aneurysm. PMID- 22070948 TI - Language, perception, and the schematic representation of spatial relations. AB - Schemas are abstract nonverbal representations that parsimoniously depict spatial relations. Despite their ubiquitous use in maps and diagrams, little is known about their neural instantiation. We sought to determine the extent to which schematic representations are neurally distinguished from language on the one hand, and from rich perceptual representations on the other. In patients with either left hemisphere damage or right hemisphere damage, a battery of matching tasks depicting categorical spatial relations was used to probe for the comprehension of basic spatial concepts across distinct representational formats (words, pictures, and schemas). Left hemisphere patients underperformed right hemisphere patients across all tasks. However, focused residual analyses using voxel-based lesion-symptom mapping (VLSM) suggest that (1) left hemisphere deficits in the representation of categorical spatial relations are difficult to distinguish from deficits in naming these relations and (2) the right hemisphere plays a special role in extracting schematic representations from richly textured pictures. PMID- 22070968 TI - Tissue microbiology provides a coherent picture of infection. AB - The vertebrate host represents an extraordinarily complex and heterogenous environment which pathogenic bacteria of different types able to colonize and infect. This implies that all contributory elements of an infected tissue type or intact host are pre-requisites for full understanding of bacterial pathogenesis. Within this context, intravital techniques allow such studies of infection under realistic conditions within the live host, and with improved detection methods another level of understanding is attained. Here we define this field as tissue microbiology, with its focus placed on monitoring and mimicking host-pathogen interaction within the dynamic micro-ecology significant for infectious niches in the live host. Such all-inclusive approaches promise to more coherently define relevant interactions and angles for disease intervention. PMID- 22070969 TI - Use of composite refocusing pulses to form spin echoes. AB - The radiofrequency pulses used in NMR are subject to a number of imperfections such as those caused by inhomogeneity of the radiofrequency (B(1)) field and an offset of the transmitter frequency from precise resonance. The effect of these pulse imperfections upon a refocusing pulse in a spin-echo experiment can be severe. Many of the worst effects, those that distort the phase of the spin echo, can be removed completely by selecting the echo coherence pathway using either the "Exorcycle" phase cycle or magnetic field gradients. It is then tempting to go further and try to improve the amplitude of the spin-echo signal by replacing the simple refocusing pulse with a broadband composite 180 degrees pulse that compensates for the relevant pulse imperfection. We show here that all composite pulses with a symmetric or asymmetric phase shift scheme will reintroduce phase distortions into the spin echo, despite the selection of the echo coherence pathway. In contrast, all antisymmetric composite pulses yield no phase distortion whatsoever, both on and off resonance, and are therefore the correct symmetry of composite refocusing pulse to use. These conclusions are verified using simulations and (31)P MAS NMR spin-echo experiments performed on a microporous aluminophosphate. PMID- 22070970 TI - Suppression of sampling artefacts in high-resolution four-dimensional NMR spectra using signal separation algorithm. AB - The development of non-uniform sampling (NUS) strategies permits to obtain high dimensional spectra with increased resolution in significantly reduced experimental time. We extended a previously proposed signal separation algorithm (SSA) to process sparse four-dimensional NMR data. It is employed for two experiments carried out for a partially unstructured 114-residue construct of chicken Engrailed 2 protein, namely 4D HCCH-TOCSY and 4D C,N-edited NOESY. The SSA allowed us to obtain high-quality spectra using only as little as 0.16% of the available samples, with low sampling artefacts approaching the thermal noise level in most spectral regions. It is demonstrated that NUS 4D HCCH-TOCSY is dominated by sampling noise and requires efficient artefact suppression. On the other hand, 4D C,N-edited NOESY is a particularly attractive experiment for NUS, as the absence of diagonal peaks renders the problem of artefacts less critical. We also present a transverse-relaxation optimized sequence for HMQC that is especially designed for longer evolution periods in the indirectly detected proton dimension in high-dimensional pulse sequences. In conjunction with novel sampling strategies and efficient processing methods, this improvement enabled us to obtain unique structural information about aliphatic-amide contacts. PMID- 22070971 TI - Comparison of interleukin IL-6 levels in the subretinal fluid and the vitreous during rhegmatogenous retinal detachment. PMID- 22070972 TI - Fibrolamellar hepatocellular carcinoma. PMID- 22070973 TI - Abscisic acid root and leaf concentration in relation to biomass partitioning in salinized tomato plants. AB - Salinization is one of the most important causes of crop productivity reduction in many areas of the world. Mechanisms that control leaf growth and shoot development under the osmotic phase of salinity are still obscure, and opinions differ regarding the Abscisic acid (ABA) role in regulation of biomass allocation under salt stress. ABA concentration in roots and leaves was analyzed in a genotype of processing tomato under two increasing levels of salinity stress for five weeks: 100 mM NaCl (S10) and 150 mM NaCl (S15), to study the effect of ABA changes on leaf gas exchange and dry matter partitioning of this crop under salinity conditions. In S15, salinization decreased dry matter by 78% and induced significant increases of Na(+) and Cl(-) in both leaves and roots. Dry matter allocated in different parts of plant was significantly different in salt stressed treatments, as salinization increased root/shoot ratio 2-fold in S15 and 3-fold in S15 compared to the control. Total leaf water potential (Psi(w)) decreased from an average value of approximately -1.0 MPa, measured on control plants and S10, to -1.17 MPa in S15. In S15, photosynthesis was reduced by 23% and stomatal conductance decreased by 61%. Moreover, salinity induced ABA accumulation both in tomato leaves and roots of the more stressed treatment (S15), where ABA level was higher in roots than in leaves (550 and 312 ng g(-1) fresh weight, respectively). Our results suggest that the dynamics of ABA and ion accumulation in tomato leaves significantly affected both growth and gas exchange related parameters in tomato. In particular, ABA appeared to be involved in the tomato salinity response and could play an important role in dry matter partitioning between roots and shoots of tomato plants subjected to salt stress. PMID- 22070974 TI - Distribution and change patterns of free IAA, ABP 1 and PM H+-ATPase during ovary and ovule development of Nicotiana tabacum L. AB - Auxin plays key roles in flower induction, embryogenesis, seed formation and seedling development, but little is known about whether auxin regulates the development of ovaries and ovules before pollination. In the present report, we measured the content of free indole-3-acetic (IAA) in ovaries of Nicotiana tabacum L., and localized free IAA, auxin binding protein 1 (ABP1) and plasma membrane (PM) H+-ATPase in the ovaries and ovules. The level of free IAA in the developmental ovaries increased gradually from the stages of ovular primordium to the functional megaspore, but slightly decreased when the embryo sacs formed. Immunoenzyme labeling clearly showed that both IAA and ABP1 were distributed in the ovules, the edge of the placenta, vascular tissues and the ovary wall, while PM H+-ATPase was mainly localized in the ovules. By using immunogold labeling, the subcellular distributions of IAA, ABP1 and PM H+-ATPase in the ovules were also shown. The results suggest that IAA, ABP1 and PM H+-ATPase may play roles in the ovary and ovule initiation, formation and differentiation. PMID- 22070975 TI - Gene families of maize glutathione-ascorbate redox cycle respond differently to abiotic stresses. AB - The glutathione-ascorbate (GSH-ASC) cycle in plants plays an important role in detoxifying reactive oxygen species. Little is known about how the enzymes and antioxidants in the maize GSH-ASC cycle respond to stress. We clarified the genome positions, exon-intron structures and predicted subcellular locations of the ascorbate peroxidase (APX), monodehydroascorbate reductase (MDAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) families in maize. ABA treatment increased the transcript levels of most of the APX genes except ZmAPX3 and ZmAPX6, upregulated the transcription of ZmMDAR1 and downregulated the transcriptions of ZmMDAR3 and ZmMDAR4. However, it had little effect on the expressions of the ZmDHAR and ZmGR gene families. ABA treatment increased the activities of only 2 enzymes, ZmAPX and ZmDHAR. The PEG treatment led to similar expression patterns as that of ABA. ZmAPX1.1 and ZmAPX2 exhibited the same expression patterns under PEG treatment conditions. Enzyme activities were not affected by the PEG treatment with the exception of a significant decrease in MDAR activity that was observed after 6h. Compared to the ABA and PEG treatments, the NaCl treatment only slightly affected the transcription of the four gene families but significantly increased the activity of ZmGR. The ABA and PEG treatments elevate the ASC levels and decrease the GSSG level. Our results show that the gene families of the maize GSH-ASC redox cycle respond differently to abiotic stresses and suggest that APX and MDAR may play more important roles in stress tolerance in plants. PMID- 22070976 TI - Time-dependent distribution of sulphur, sulphate and glutathione in wheat tissues and grain as affected by three sulphur fertilization levels and late S fertilization. AB - Sulphur (S) fertilization has beneficial effects on yield and protein composition of mature wheat kernels. However, to understand the impact of S fertilization on storage protein composition, synthesis of S-containing compounds and their distribution during grain development has to be examined. A pot experiment with Triticum aestivum cultivar Turkis under three S fertilization levels (0 g, 0.1 g und 0.2 g S per pot) and a late S fertilization level at ear emergence was carried out. Stalk and leaves, flag leaves, ears and kernels were harvested separately during grain development at ear emergence, milk ripeness and maturity, and analyzed for elemental S, sulphate, glutathione, and protein concentration. Sulphate is the major S compound in stalk, leaf and ears at the start of grain development, whereas glutathione is more important for synthesis of S-containing proteins in the grain. The discrepancy of S concentration comparing low and high S fertilization became obvious after milk ripeness. The N/S ratios in ears at ear emergence and milk ripeness reflected the later N/S ratio in mature grain. Late S fertilization increased sulphate concentrations in the flag leaf within a short period of about two weeks at ear emergence. Late S fertilization prevented S deficiency in late stages of wheat growth and further enabled equal concentrations of S, glutathione and protein in all wheat organs compared to an S application only at sowing. PMID- 22070977 TI - Identification of differentially expressed salt-responsive proteins in roots of two perennial grass species contrasting in salinity tolerance. AB - This study was designed to identify physiological responses and differential proteomic responses to salinity stress in roots of a salt-tolerant grass species, seashore paspalum (Paspalum vaginatum), and a salt-sensitive grass species, centipedegrass (Eremochloa ophiuroides). Plants of both species were exposed to salinity stress by watering the soil with 300 mM NaCl solution for 20 d in a growth chamber. The 2-DE analysis revealed that the abundance of 8 protein spots significantly increased and 14 significantly decreased in seashore paspalum, while 19 and 16 protein spots exhibited increase and decrease in abundance in centipedegrass, respectively. Eight protein spots that exhibited enhanced abundance in seashore paspalum under salinity stress were subjected to mass spectrometry analysis. Seven protein spots were successfully identified, they are peroxidase (POD, 2.36-fold), cytoplasmic malate dehydrogenase (cMDH, 5.84-fold), asorbate peroxidase (APX, 4.03-fold), two mitochondrial ATPSdelta chain (2.26 fold and 4.78-fold), hypothetical protein LOC100274119 (5.01-fold) and flavoprotein wrbA (2.20-fold), respectively. Immunblotting analysis indicated that POD and ATPSdelta chain were significantly up-regulated in seashore paspalum at 20 d of salinity treatment while almost no expression in both control and salt treatment of centipedegrass. These results indicated that the superior salinity tolerance in seashore paspalum, compared to centipedegrass, could be associated with a high abundance of proteins involved in ROS detoxification and energy metabolism. PMID- 22070978 TI - Effects of undenatured whey protein supplementation on CXCL12- and CCL21-mediated B and T cell chemotaxis in diabetic mice. AB - BACKGROUND: Long and persistent uncontrolled diabetes tends to degenerate the immune system and leads to an increased incidence of infection. Whey proteins (WPs) enhance immunity during early life and have a protective role in some immune disorders. In this study, the effects of camel WP on the chemotaxis of B and T cells to CXCL12 and CCL21 in diabetic mice were investigated. RESULTS: Flow cytometric analysis of the surface expressions of CXCR4 (CXCL12 receptor) and CCR7 (CCL21 receptor) on B and T cells revealed that the surface expressions of CXCR4 and CCR7 were not significantly altered in diabetic and WP-supplemented diabetic mice compared with control mice. Nevertheless, B and T lymphocytes from diabetic mice were found to be in a stunned state, with a marked and significant (P < 0.05) decrease in CXCL12- and CCL21-mediated actin polymerization and subsequently, a marked decrease in their chemotaxis. WP supplementation in the diabetes model was found to significantly increase CXCL12- and CCL21-mediated actin polymerization and chemotaxis in both B and T cells. CONCLUSION: Our data revealed the benefits of WP supplementation in enhancing cytoskeletal rearrangement and chemotaxis in B and T cells, and subsequently improving the immune response in diabetic mice. PMID- 22070979 TI - Incorporation of in situ exposure and biomarkers response in clams Ruditapes philippinarum for assessment of metal pollution in coastal areas from the Maluan Bay of China. AB - The clams Ruditapes philippinarum were used to assess the impact of metal contaminants when transplanted to seven study sites along the Maluan Bay (China). Metal concentrations in digestive gland tissues of clams after 7-day in situ cage exposure were determined in conjunction with antioxidant enzyme activities. The results showed the importance of specific antioxidant biomarkers to assess complex pollutant mixtures and their good correlations to the pollutant compositions of deployment sites. Multivariate analysis indicated causal relationship between the chemicals at each study site and the biochemical "response" of the caged clams at these sites and demonstrated the potential presence of two different contaminant sources. This study suggested that the incorporation of tissue residue analysis with biomarkers response in caged clams together with factor analysis can be a useful biomonitoring tool for the identification of causal toxic pollutants and the assessment of complex metal pollutions in marine coastal environment. PMID- 22070980 TI - Quantifying the sources of pollutants in the Great Barrier Reef catchments and the relative risk to reef ecosystems. AB - Development of the Great Barrier Reef (GBR) catchments in the last 150 years has increased the loads of suspended sediment, nutrients and pesticides ('pollutants') delivered to the GBR. The scale and type of development, the pollutants generated and the ecosystems offshore vary regionally. We analysed the relative risk of pollutants from agricultural land uses and identified the sources of these pollutants from different land uses for each region to develop priorities for management. The assessment showed the Wet Tropics and Mackay Whitsunday regions to be of relatively high risk dominated by sugarcane cultivation, contributing pesticide and dissolved inorganic nitrogen (DIN). The Burdekin and Fitzroy ranked medium-high risk dominated by grazing suspended sediment inputs for both, and additionally sugarcane DIN and pesticide inputs for the Burdekin. The Burnett Mary ranked medium risk, dominated by grazing and sugarcane. Cape York was not formally ranked but is considered to be low risk. PMID- 22070981 TI - Biomarker responses in Atlantic cod (Gadus morhua) exposed to produced water from a North Sea oil field: laboratory and field assessments. AB - Biological markers of produced water (PW) exposure were studied in Atlantic cod (Gadus morhua) in both laboratory and field experiments, using authentic PW from a North Sea oil field. In the laboratory study, the PW exposure yielded significantly elevated levels of metabolites of polycyclic aromatic hydrocarbons (PAHs) and alkylphenols (APs) in bile even at the lowest exposure dose (0.125% PW). Other biomarkers (hepatic CYP1A induction and DNA adduct formation) responded at 0.25% and 0.5% PW concentrations. In the field study, bile metabolite markers and hepatic CYP1A were clearly increased in fish caged close to the PW outfall. Induction of plasma vitellogenin was not found in laboratory or field exposures, suggesting that the levels of oestrogen agonists (such as APs) might not have been sufficient to elicit induction, under the present conditions. The applicability of the biomarkers for use in water column biomonitoring programs is discussed. PMID- 22070982 TI - The relationship between heart rate variability and time-course of carcinoembryonic antigen in colorectal cancer. AB - BACKGROUND: Identifying new prognostic factors is important for guiding treatments and preventing metastasis in cancer. Vagal nerve activity may predict prognosis in cancer due to its roles in modulating inflammation, sympathetic activity and oxidative stress. This study tested the relationship between heart rate variability (HRV), a vagal nerve index, and the colon cancer (CC) marker carcinoembryonic antigen (CEA), in an 'historical prospective' design. METHODS: We examined data of 72 CC patients, without inflammatory or cardiac diseases, of whom 38 had baseline electrocardiograms (ECG) and 12 month CEA levels. We measured HRV (SDNN, RMSSD) from brief archived ECG. Multiple confounders were considered. RESULTS: Controlling for effects of tumor stage and treatment orientation, baseline HRV predicted CEA levels at 12 months (r=-.43, p=.006). Patients with SDNN<20 ms had significantly higher CEA at 12months than those with SDNN>20 ms. CONCLUSION: These preliminary results showed that higher HRV predicts lower levels of a tumor marker, one year later, independent of confounders. This supports the hypothesized role of vagal activity in tumor modulation. Replication in larger samples is needed. PMID- 22070983 TI - Calcium supplementation prevents obesity, hyperleptinaemia and hyperglycaemia in adult rats programmed by early weaning. AB - It is known that Ca therapy may have anti-obesity effects. Since early weaning leads to obesity, hyperleptinaemia and insulin resistance, we studied the effect of dietary Ca supplementation in a rat model. Lactating rats were separated into two groups: early weaning (EW) - dams were wrapped with a bandage to interrupt lactation in the last 3 d of lactation and control (C) - dams whose pups had free access to milk during the entire lactation period (21 d). At 120 d, EW and C offspring were subdivided into four groups: (1) C, received standard diet; (2) CCa, received Ca supplementation (10 g of calcium carbonate/kg of rat chow); (3) EW, received standard diet; (4) EWCa, received Ca supplementation similar to CCa. The rats were killed at 180 d. The significance level was at P < 0.05. Adult EW offspring displayed hyperphagia (28 %), higher body weight (9 %) and adiposity (77 %), hyperleptinaemia (twofold increase), hypertriacylglycerolaemia (64 %), hyperglycaemia (16 %), higher insulin resistance index (38 %) and higher serum 25 hydroxyvitamin D3 (fourfold increase), but lower adiponectinaemia:adipose tissue ratio (44 %). In addition, they showed Janus tyrosine kinase 2 and phosphorylated signal transducer and activator of transcription 3 underexpression in hypothalamus (36 and 34 %, respectively), suggesting leptin resistance. Supplementation of Ca for 2 months normalised these disorders. The EW group had no change in serum insulin, thyroxine or triiodothyronine, and Ca treatment did not alter these hormones. In conclusion, we reinforced that early weaning leads to late development of some components of the metabolic syndrome and leptin resistance. Dietary Ca supplementation seems to protect against the development of endocrine and metabolic disorders in EW offspring, maybe through vitamin D inhibition. PMID- 22070985 TI - European regulation of herbal medicinal products on the border area to the food sector. AB - This article summarizes the regulation of herbal medicinal products in the EU with emphasis on traditional herbal medicinal products (THMP) and provides an evaluation of the borderline between medicine and food. Differences in the regulation of THMP with influence on the harmonization are revealed. With regard to the borderline between medicine and food, THMP may not be medicinal products by function but by presentation. The thesis is established that depending on the presentation, the product can be medicine (THMP) as well as food. To avoid shifting into the food sector the regulatory system of THMP is evaluated with regard to its attractiveness to applicants. Recommendations to achieve a better harmonization of THMP in the EU and to increase the attractiveness of the simplified registration procedure are given. PMID- 22070984 TI - DNA vaccination with a gene encoding Toxoplasma gondii GRA6 induces partial protection against toxoplasmosis in BALB/c mice. AB - BACKGROUND: Infection with the protozoan Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. Protection from acute toxoplasmosis is known to be mediated by CD8+ T cells, but the T. gondii antigens and host genes required for eliciting protective immunity have been poorly defined. The T. gondii dense granule protein 6 (GRA6), recently proved to be highly immunogenic and produces fully immune protection in T. gondii infected BALB/c mice with an H-2Ld gene. The CD8+ T cell response of H-2Ld mice infected by the T. gondii strain seemed to target entirely to a single GRA6 peptide HF10-H 2Ld complex. RESULTS: To determine whether a GRA6-based DNA vaccine can elicit protective immune responses to T. gondii in BALB/c mice, we constructed a eukaryotic expression vector pcDNA3.1-HisGRA6 and tested its immunogenicity in a mouse model. BALB/c mice were vaccinated intramuscularly with three doses of GRA6 DNA and then challenged with a lethal dose of T. gondii RH strain tachyzoites. All immunized mice developed high levels of serum anti-GRA6 IgG antibodies, and in vitro splenocyte proliferation was strongly enhanced in mice adjuvanted with levamisole (LMS). Immunization with pcDNA3.1-HisGRA6 with LMS resulted in 53.3% survival of challenged BALB/c mice as compared to 40% survival of BALB/c without LMS. Additionally, immunized Kunming mice without an allele of H-2Ld failed to survive. CONCLUSIONS: Our result supports the concept that the acquired immune response is MHC restricted. This study has a major implication for vaccine designs using a single antigen in a population with diverse MHC class I alleles. PMID- 22070986 TI - Psychopharmacological profile of Chamomile (Matricaria recutita L.) essential oil in mice. AB - In this study, the effect of Matricaria recutita L. essential oil (MEO) on the central nervous system (CNS) of mice was investigated using some behavioral methods. Chemical profiling both by GC and GC-MS analyses of the hydrodistilled essential oil of M. recutita revealed alpha-bisabolol oxide A (28%), alpha bisabolol oxide B (17.1%), (Z)-beta-Farnesene (15.9%) and alpha-bisabolol (6.8%) as the main components. Changes induced by MEO (25, 50 and 100 mg/kg) and reference drug caffeine (25 mg/kg) in spontaneous locomotor activities and motor coordinations of mice were investigated by activity cage measurements and Rota Rod tests, respectively. Open field, social interaction and elevated plus-maze tests were applied to assess the emotional state of the animals. Further, tail suspension test was performed for evaluating the effect of MEO on depression levels of mice. As a result, at 50 and 100 mg/kg, MEO significantly increased the numbers of spontaneous locomotor activities, exhibited anxiogenic effect in the open field, elevated plus-maze and social interaction tests and decreased the immobility times of animals in tail suspension tests. The falling latencies in Rota-Rod tests did not change. This activity profile of MEO was similar to the typical psychostimulant caffeine. The exact mechanism of action underlying this stimulant-like effect should be clarified with further detailed studies. PMID- 22070987 TI - Women with disabilities' experience with physical and sexual abuse: review of the literature and implications for the field. AB - While studies suggest that the rate of abuse of women with disabilities is similar or higher compared to the general population, there continues to be a lack of attention to this issue. Women with disabilities are at particularly high risk of abuse, both through typical forms of violence (physical, sexual, and emotional) and those that target one's disability. In an effort to highlight the need for increased attention to this issue, this article reviews the current peer reviewed research in this field. The authors outline recommendations for future research goals and provide implications for research, practice, and policy. PMID- 22070988 TI - Parenting interventions for male young offenders: a review of the evidence on what works. AB - Approximately one in four incarcerated male young offenders in the UK is an actual or expectant father. This paper reviews evidence on the effectiveness of parenting interventions for male young offenders. We conducted systematic searches across 20 databases and consulted experts. Twelve relevant evaluations were identified: 10 from the UK, of programmes for incarcerated young offenders, and two from the US, of programmes for young parolees. None used experimental methods or included a comparison group. They suggest that participants like the courses, find them useful, and the interventions may improve knowledge about, and attitudes to, parenting. Future interventions should incorporate elements of promising parenting interventions with young fathers in the community, for example, and/or with older incarcerated parents. Young offender fathers have specific developmental, rehabilitative, and contextual needs. Future evaluations should collect longer-term behavioural parent and child outcome data and should use comparison groups and, ideally, randomization. PMID- 22070989 TI - International casemix and funding models: lessons for rehabilitation. AB - This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is 'An understanding of the different international models for funding of health care services and casemix systems, as exemplified by those in the US, Australia and the UK.' BACKGROUND: Payment for treatment in healthcare systems around the world is increasingly based on fixed tariff models to drive up efficiency and contain costs. Casemix classifications, however, must account adequately for the resource implications of varying case complexity. Rehabilitation poses some particular challenges for casemix development. OBJECTIVE: The objectives of this educational narrative review are (a) to provide an overview of the development of casemix in rehabilitation, (b) to describe key characteristics of some well-established casemix and payment models in operation around the world and (c) to explore opportunities for future development arising from the lessons learned. RESULTS: Diagnosis alone does not adequately describe cost variation in rehabilitation. Functional dependency is considered a better cost indicator, and casemix classifications for inpatient rehabilitation in the United States and Australia rely on the Functional Independence Measure (FIM). Fixed episode-based prospective payment systems are shown to contain costs, but at the expense of poorer functional outcomes. More sophisticated models incorporating a mixture of episode and weighted per diem rates may offer greater flexibility to optimize outcome, while still providing incentive for throughput. CONCLUSION: The development of casemix in rehabilitation poses similar challenges for healthcare systems all around the world. Well-established casemix systems in the United States and Australia have afforded valuable lessons for other countries to learn from, but have not provided all the answers. A range of casemix and payment models is required to cater for different healthcare cultures, and casemix tools must capture all the key cost-determinants of treatment for patients with complex needs. PMID- 22070991 TI - Inviting the pharmacist: a model for improved reproductive care access. PMID- 22070990 TI - Effectiveness of constraint-induced movement therapy on activity and participation after stroke: a systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVE: To examine the effect of constraint-induced movement therapy and modified constraint-induced movement therapy on activity and participation of patients with stroke (i.e. the effect of different treatment durations and frequency) by reviewing the results of randomized controlled trials. DATA SOURCES: A systematic literature search was conducted in MEDLINE, CINAHL, EMBASE, PEDro, OTSeeker, CENTRAL and by manual search. REVIEW METHODS: Randomized controlled trials for patients over 18 years old with stroke and published in Finnish, Swedish, English or German were included. Studies were collected up to the first week in May 2011. The evidence was high, moderate, low or no evidence according to the quality of randomized controlled trial and the results of meta analyses. RESULTS: Search resulted in 30 papers reporting constraint-induced movement therapy, including 27 randomized controlled trials published between 2001 and 2011. Constraint-induced movement therapy practice for 60-72 hours over two weeks produced better mobility (i.e. ability to carry, move and handle objects) with high evidence compared to control treatment. Constraint-induced movement therapy for 20-56 hours over two weeks, 30 hours over three weeks and 15 30 hours over 10 weeks improved mobility of the affected upper extremity. However, with self-care as an outcome measure, only 30 hours of constraint induced movement therapy practice over three weeks demonstrated an improvement. CONCLUSION: Constraint-induced movement therapy and modified constraint-induced movement therapy proved to be effective on affected hand mobility and to some extent self-care on the World Health Organization's International Classification of Functioning, Disability and Health activity and participation component, but further studies are needed to find out the optimal treatment protocols for constraint-induced movement therapy. PMID- 22070992 TI - Optical and spectroscopic studies on tannery wastes as a possible source of organic semiconductors. AB - Tanning industry produces a large quantity of solid wastes which contain hide proteins in the form of protein shavings containing chromium salts. The chromium wastes are the main concern from an environmental stand point of view, because chrome wastes posses a significant disposal problem. The present work is devoted to investigate the possibility of utilizing these wastes as a source of organic semi-conductors as an alternative method instead of the conventional ones. The chemical characterization of these wastes was determined. In addition, the Horizontal Attenuated Total Reflection (HATR) FT-IR spectroscopic analysis and optical parameters were also carried out for chromated samples. The study showed that the chromated samples had suitable absorbance and transmittance in the wavelength range (500-850 nm). Presence of chromium salt in the collagen samples increases the absorbance which improves the optical properties of the studied samples and leads to decrease the optical energy gap. The obtained optical energy gap gives an impression that the environmentally hazardous chrome shavings wastes can be utilized as a possible source of natural organic semiconductors with direct and indirect energy gap. This work opens the door to use some hazardous wastes in the manufacture of electronic devices such as IR-detectors, solar cells and also as solar cell windows. PMID- 22070993 TI - DFT studies on some properties of maleonitriledithiolate complexes [M(mnt)2]2- (M=Ni, Pd, Pt and Zn, Cd, Hg). AB - The structures and some molecular properties of the complexes M(mnt)(2)(2-) (M=Ni, Pd, Pt and Zn, Cd, Hg; mnt(2-)=deprotonated maleonitriledithiolate) have been studied by using density functional theory (DFT) B3LYP/LanL2DZ level of theory. Computed binding energies show that the sequences of binding strengths are Ni0.05). Studies showed that there was no relationship between seroprevalence and the gender (P >0.05). CONCLUSIONS: The present survey indicated the high seroprevalence of T. gondii in cats in Lanzhou, northwest China, which poses a threat to animal and human health. Therefore, measures should be taken to control and prevent toxoplasmosis of cats in this area. PMID- 22071005 TI - Global transcriptome analysis of Bacillus cereus ATCC 14579 in response to silver nitrate stress. AB - Silver nanoparticles (AgNPs) were synthesized using Bacillus cereus strains. Earlier, we had synthesized monodispersive crystalline silver nanoparticles using B. cereus PGN1 and ATCC14579 strains. These strains have showed high level of resistance to silver nitrate (1 mM) but their global transcriptomic response has not been studied earlier. In this study, we investigated the cellular and metabolic response of B. cereus ATCC14579 treated with 1 mM silver nitrate for 30 & 60 min. Global expression profiling using genomic DNA microarray indicated that 10% (n = 524) of the total genes (n = 5234) represented on the microarray were up regulated in the cells treated with silver nitrate. The majority of genes encoding for chaperones (GroEL), nutrient transporters, DNA replication, membrane proteins, etc. were up-regulated. A substantial number of the genes encoding chemotaxis and flagellar proteins were observed to be down-regulated. Motility assay of the silver nitrate treated cells revealed reduction in their chemotactic activity compared to the control cells. In addition, 14 distinct transcripts overexpressed from the 'empty' intergenic regions were also identified and proposed as stress-responsive non-coding small RNAs. PMID- 22071007 TI - A seasonal survey of gastrointestinal parasites in captive wild impala antelope on a game facility south of Lusaka, Zambia. AB - Faecal samples (n = 1947) from captive wild impala (Aepyceros melampus melampus) were examined over a period of 14 months to determine quantitative seasonal helminth egg excretion patterns and qualitative protozoan oocyst excretion patterns. Geometric mean monthly faecal egg counts (FECs) ranged from 20 to 575 and coprocultures revealed three parasite genera, namely Trichostrongylus, Haemonchus and Strongyloides. Larvae of the Trichostrongylus spp. were most predominant from faecal cultures. No trematode eggs or lungworms were detected and eggs of the cestode Monezia were only seen in two samples during the entire study period. The nematode FECs showed a marked seasonal variation, being higher during the rainy season, moderate during the cool dry season and low during the hot dry season. The rainy season had significantly higher FECs than the dry season (P < 0.01). The percentage of helminth-egg positive faecal samples ranged from 90.6 to 100% in the rainy season and 72.4 to 85.6% in the dry season. Overall mean FECs in unpelleted faeces were significantly higher than in pelleted faeces (P < 0.01). However, the FECs were not significantly different among seasons in unpelleted faeces (P>0.05), but were significantly higher in pelleted faeces in the rainy season than the dry season (P < 0.05). Pellet size had a significant effect on FEC, with smaller pellets having higher FEC (P < 0.05). Strongyloides eggs and coccidia oocysts were only seen during the rainy season. This represents the first documentation of seasonal parasitic infestation in captive wild antelopes in Zambia. Treatment and control strategies for helminths in these captive wild impala are also suggested based on the findings from this study. PMID- 22071008 TI - Effect of omega-3 fatty acids on the modification of erythrocyte membrane fatty acid content including oleic acid in peritoneal dialysis patients. AB - Erythrocyte membrane fatty acids (FA), such as oleic acid, are related to acute coronary syndrome. There is no report about the effect of omega-3 FA on oleic acid in peritoneal dialysis (PD) patients. We hypothesized that omega-3 FA can modify erythrocyte membrane FA, including oleic acid, in PD patients. In a double blind, randomized, placebo-controlled study, 18 patients who were treated with PD for at least 6 months were randomized to treatment for 12 weeks with omega-3 FA or placebo. Erythrocyte membrane FA content was measured by gas chromatography at baseline and after 12 weeks. The erythrocyte membrane content of eicosapentaenoic acid and docosahexaenoic acid was significantly increased and saturated FA and oleic acid were significantly decreased in the omega-3 FA supplementation group after 12 weeks compared to baseline. In conclusion, erythrocyte membrane FA content, including oleic acid, was significantly modified by omega-3 FA supplementation for 12 weeks in PD patients. PMID- 22071010 TI - In defence of our research on competition in England's National Health Service. PMID- 22071009 TI - Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women. AB - Intravenous glucose tolerance tests have demonstrated lower whole-body insulin sensitivity (S(I)) among African Americans (AA) compared with European Americans (EA). Whole-body S(I) represents both insulin-stimulated glucose disposal, primarily by skeletal muscle, and insulin's suppression of endogenous glucose production (EGP) by liver. A mathematical model was recently introduced that allows for distinction between disposal and hepatic S(I). The purpose of this study was to examine specific indexes of S(I) among AA and EA women to determine whether lower whole-body S(I) in AA may be attributed to insulin action at muscle, liver, or both. Participants were 53 nondiabetic, premenopausal AA and EA women. Profiles of EGP and indexes of Disposal S(I) and Hepatic S(I) were calculated by mathematical modeling and incorporation of a stable isotope tracer ([6,6-(2)H(2)]glucose) into the intravenous glucose tolerance test. Body composition was assessed by dual-energy x-ray absorptiometry. After adjustment for percentage fat, both Disposal S(I) and Hepatic S(I) were lower among AA (P = .009 for both). Time profiles for serum insulin and EGP revealed higher peak insulin response and corresponding lower EGP among AA women compared with EA. Indexes from a recently introduced mathematical model suggest that lower whole body S(I) among nondiabetic AA women is due to both hepatic and peripheral components. Despite lower Hepatic S(I), AA displayed lower EGP, resulting from higher postchallenge insulin levels. Future research is needed to determine the physiological basis of lower insulin sensitivity among AA and its implications for type 2 diabetes mellitus risk. PMID- 22071011 TI - Effects of two different levels of computerized decision support on blood glucose regulation in critically ill patients. AB - INTRODUCTION: Although the use of computerized decision support systems (CDSS) in glucose control in the ICU has been reported, little is known about the effect of the systems' operating modes on the quality of glucose control. The objective of this study was to evaluate the effect of providing patient-specific and patient non-specific computerized advice on timing of blood glucose level (BGL) measurements. Our hypothesis was that both levels of support would be effective for improving the quality of glucose regulation and safety, with patient specific advice being the most effective strategy. PATIENTS AND METHODS: A prospective study was performed in a 30-bed mixed medical-surgical intensive care unit (ICU) of a university hospital. In phase 1 the CDSS provided non-specific advice and thereafter, in phase 2, the system provided specific advice on timing of BGL measurements. The primary outcome measure was delay in BGL measurements before and after the two levels of support. Secondary endpoints were sampling frequency, mean BGL, BGL within pre-defined targets, time to capture target, incidences of severe hypoglycemia and hyperglycemia. These indicators were analyzed over the course of time using Statistical Control Charts. The analysis was restricted to patients with at least two blood glucose measurements. RESULTS: Data of 3934 patient admissions were evaluated, which corresponded to 119,116 BGL measurements. The BGL sampling interval, delays in BG sampling, and percentage of hypoglycemia all decreased after introducing either of the two levels of decision support. The effect was however larger for the patient specific CDSS. Mean BGL, time to capture target, hyperglycemia index, percentage of hyperglycemia events and "in range" measurements remained unchanged and stable after introducing both patient non-specific and patient specific decision support. CONCLUSION: Adherence to protocol sampling rules increased by using decision support with a larger effect at the patient specific level. This led to a decrease in the percentage of hypoglycemia events and improved safety. The use of the CDSS at both levels, however, did not improve the quality of glucose control as measured by our indicators. More research is needed to investigate whether other socio-technical factors are in play. PMID- 22071012 TI - Do hospital physicians' attitudes change during PACS implementation? A cross sectional acceptance study. AB - PURPOSE: The purpose of this study is to gain a better insight into the reasons why hospital physicians accept and use a Picture Archiving and Communication System (PACS). Two research questions are put forward, pertaining to (1) factors that contribute to physicians' acceptance of PACS, and (2) whether these factors change as physicians gain experience in using PACS. METHODS: Questionnaires were administered at three moments in time during the PACS implementation process in a private hospital: just before its introduction (T1), four months later (T2), and about fifteen months after the introduction of PACS (T3). The Unified Theory of Acceptance and Use of Technology was chosen as the theoretical framework for this study. Hence, the following scales were measured: performance expectancy, effort expectancy, social influence, facilitating conditions, behavioral intention, and self-reported frequency of use. RESULTS: Forty-six usable responses were obtained at T1, 52 at T2 and 61 at T3. Three variables directly influenced PACS acceptance (measured as behavioral intention and use of PACS): effort expectancy, performance expectancy, and social influence; and their influence evolved over time. Effort expectancy was of particular importance at T1, whereas performance expectancy influenced acceptance at T2 and T3; social influence was the only consistent predictor of PACS acceptance at all times. Variance explained in behavioral intention ranged from .26 at T1 to .58 at T3. CONCLUSIONS: In this setting, the main motivation for physicians to start using PACS is effort expectancy, whereas performance expectancy only becomes important after the physicians started using PACS. It is also very important that physicians perceive that their social environment encourages the use of PACS. PMID- 22071013 TI - Factors affecting trajectory patterns of self-rated health (SRH) in an older population--a community-based longitudinal study. AB - Self-rated health (SRH) is considered a relevant and important predictor for major health outcomes in the older population. SRH status may interact with certain factors and change over a person's lifetime. In this study, we sought to characterize profiles of older people over time by constructing prototypical trajectories of the variable of interest, namely SRH. The underlying assumption was that the collection of observed individual trajectories could be efficiently summarized by a smaller set of latent clusters of those trajectories. Data was obtained from the Longitudinal Survey of Health and Living Status of the Elderly in Taiwan, which was conducted between 1989 and 2003 and included five separate waves of survey. A total of 3937 subjects aged 60 or older (2251 males and 1686 females) comprised the major analytic cohort. Latent Class Growth Analysis (LCGA) was used to identify developmental classes of trajectory patterns in SRH. The results showed that during a 14-year period, SRH developed five major longitudinal trajectories. Less than one-third of the older population was able to maintain their formerly good or moderate health status; when change occurred, decline was more likely than improvement. In addition, LCGA indicated that many demographic characteristics, as well as physical and psychological propensities, were associated with poor SRH in the older population. Specifically, these factors played a role in involving baseline SRH level and its trend toward deterioration in later life. Health care professionals must understand the various longitudinal patterns and factors affecting SRH trajectories if they are to develop programs aimed at maintaining the older population's health and well being. PMID- 22071014 TI - Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. AB - STUDY OBJECTIVE: This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention. METHODS: This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury. Blood samples were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP (nanograms/milliliter). RESULTS: Of the 307 patients enrolled, 108 were patients with traumatic brain injury (97 with GCS score 13 to 15 and 11 with GCS score 9 to 12) and 199 were controls (176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls). Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 (95% confidence interval [CI] 0.86 to 0.94) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 (95% CI 0.82 to 0.93). Thirty-two patients with traumatic brain injury (30%) had lesions on CT. The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 (95% CI 0.69 to 0.89). Moreover, the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 (95% CI 0.77 to 0.96). CONCLUSION: GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity, including the GCS score, CT lesions, and neurosurgical intervention. Further study is required to validate these findings before clinical application. PMID- 22071015 TI - [Role of medical treatment for symptomatic leiomyoma management in premenopausal women]. AB - The most frequent symptom with leiomyoma is menometrorrhagia. However, it can be responsible of pelvic pain, dysmenorrhea or urinary and digestive compression when it is particularly voluminous. These recommandations were made in order to review medical management of fibroids. If no therapy is able to have them disappear, various drugs may reduce their related symptoms. Tranexamic acid, non steroidal anti-inflammatory drugs and high dose of oestrogen may be useful in the management of acute hemorrhagic disorders. Progestin, such as lynestrenol induces small reduction in leiomyoma volume and moderate increase in hemoglobin level before surgery. Pregnane and nor-pregnane may improve menstrual bleeding in short or mild delays. The use of Gonadotropin Releasing Hormone (GnRH) agonists can reduce menstrual bleeding with hemoglobin recovery. Add-back therapy using tibolone seems interesting since secondary effects encountered with GnRH agonists may be reduced. Levonorgestrel-releasing intrauterine system is proven to reduce increased menstrual bleeding and restore hemoglobin level. Aminoglutethimide and fadrozole have been underevaluated to conclude when letrozole seems as efficient as GnRH agonists to reduce leiomyoma volume and provide less hot flushes. Anastrozol is associated with reduction in leiomyomata volume, pain and menstrual bleeding. Mifepristone reduces the size of uterine leiomyomata, improves symptomatology, but could be associated with development of endometrial hyperplasia. SPRM evaluated in females have shown to improve leiomyoma related symptomatology. Danazol could be useful to reduce leiomyoma related symptoms in short terms. Tamoxifen and raloxifen show modest overall benefit. Because of insufficient data concerning fulvestrant, pirfenidone or interferon, their prescription cannot be recommended in patients with leiomyomata. PMID- 22071016 TI - ["Postpartum psychosis": did you check blood ammonia level?]. PMID- 22071017 TI - [Assessment of the benefit-harm balance depending on gestationnal age to induce delivery for post-term pregnancies]. AB - OBJECTIVES: To attempt to determine for post-term pregnancies the optimal gestational age when the benefit-harm balance is in favor of induction labor in comparison with an expectative management including close monitoring. METHODS: Articles were searched using PubMed, Embase and Cochrane library. RESULTS: Current literature data are insufficient to demonstrate that routine labor induction is superior, inferior or equivalent to an expectant management to reduce maternal and perinatal mortality and morbidity (EL2). Although it is impossible to determine certainly a gestational age for which the benefit-harm balance is in favor of induction labor, epidemiological data regarding the perinatal mortality suggest that an expectant management is an unreasonable option after 42 completed weeks (EL3). Current data are insufficient to state positively or negatively that routine labor induction is associated significantly to a lower rate of cesarean delivery in comparison with an expectant management (EL2). There is no evidence of a statistically significant difference in the risk of cesarean section between the two policies for women with favorable cervices (Bishop score >= 5) (EL2). CONCLUSIONS: Induction of labor at 41(+0) to 42(+6)weeks should be proposed to women with uncomplicated post-term pregnancies (EL2). The optimal age gestionnal for induction will depend mainly on maternal characteristics (EL4), but also on women's preferences and organization of maternity cares, after having delivered information regarding the benefits and harms of both labor induction and expectant management (expert opinion). After 42(+0)weeks, expectant management is a possible option (expert opinion). Nevertheless, it may be associated with an increase of risks for the fetus, that must be explained to the patient and be weighed against the possible disadvantages of an induction of labor (expert opinion). PMID- 22071018 TI - [Laparoscopic colorectal resection for deep pelvic endometriosis: Evaluation of post-operative outcome]. AB - OBJECTIVES: Evaluation of mid-term functional results and the quality of life after laparoscopic colorectal resection. PATIENTS AND METHODS: Twenty-three consecutive patients were included in a retrospective monocentric study. Postoperative functional outcomes and quality of life were analyzed. RESULTS: The median follow-up after colorectal resection was of 24+/-15.7 months (6-72). Major complications occurred in three cases (12,9%) including one anastomotic stenosis, one digestive and one bladder fistula. A significant improvement in pelvic pain symptoms was observed. De novo constipation and pain on defecation occurred in respectively 23% and 42% of the cases. Transient de novo dysuria occurred in 18% of the cases. The quality of life has been significantly improved. CONCLUSION: Laparoscopic colorectal resection is associated with unfavourable postoperative digestive and urological outcomes, such as bladder and rectal dysfunction. Radical treatment should be limited to selected patients. PMID- 22071019 TI - Screening and identification of a renal carcinoma specific peptide from a phage display peptide library. AB - BACKGROUND: Specific peptide ligands to cell surface receptors have been extensively used in tumor research and clinical applications. Phage display technology is a powerful tool for the isolation of cell-specific peptide ligands. To screen and identify novel markers for renal cell carcinoma, we evaluated a peptide that had been identified by phage display technology. METHODS: A renal carcinoma cell line A498 and a normal renal cell line HK-2 were used to carry out subtractive screening in vitro with a phage display peptide library. After three rounds of panning, there was an obvious enrichment for the phages specifically binding to the A498 cells, and the output/input ratio of phages increased about 100 fold. A group of peptides capable of binding specifically to the renal carcinoma cells were obtained, and the affinity of these peptides to the targeting cells and tissues was studied. RESULTS: Through a cell-based ELISA, immunocytochemical staining, immunohistochemical staining, and immunofluorescence, the Phage ZT-2 and synthetic peptide ZT-2 were shown to specifically bind to the tumor cell surfaces of A498 and incision specimens, but not to normal renal tissue samples. CONCLUSION: A peptide ZT-2, which binds specifically to the renal carcinoma cell line A498 was selected from phage display peptide libraries. Therefore, it provides a potential tool for early diagnosis of renal carcinoma or targeted drug delivery in chemotherapy. PMID- 22071021 TI - Children and drug law reform. PMID- 22071020 TI - High tie versus low tie of the inferior mesenteric artery: a protocol for a systematic review. AB - In anterior resection of rectum, the section level of inferior mesenteric artery is still subject of controversy between the advocates of high and low tie. The low tie is the division and ligation to the branching of the left colic artery and the high tie is the division and ligation at its origin at the aorta. We intend to assess current scientific evidence in literature and to establish the differences comparing technique, anatomy and physiology. The aim of this protocol is to achieve a meta-analysis that tests safety and feasibility of the two procedures with several types of outcome measures. PMID- 22071022 TI - The development of PCR methodology for the identification of species of the tapeworm Moniezia from cattle, goats and sheep in central Vietnam. AB - The aims of this study were to investigate the prevalence of Moniezia spp. in domestic ruminants in central Vietnam and to develop a polymerase chain reaction (PCR) technique to distinguish M. expansa from M. benedeni. Among 2040 examined domestic animals (540 cattle, 800 goats, 700 sheep) Moniezia was recovered from 5.4% of cattle, 16.4% of sheep and 20.6% of goats. A set of primers for PCR was designed to classify M. expansa and M. benedeni based on the amplification of DNA corresponding to the internal transcribed spacer of 5.8S rRNA. The 457 specimens (75 from cattle, 162 from goats, 150 from sheep, 30 from horses, 30 from chickens and 10 from dogs) were subjected to PCR for classification of Moniezia spp. PCR products with the expected sizes were amplified from bovine, ovine and caprine specimens. No specific PCR products were found for specimens from horses, chickens and dogs. Of the 75 specimens from cattle, nine were classified as M. expansa and 66 were M. benedeni. Among 162 caprine specimens, 138 were M. expansa and 24 were M. benedeni. The distribution of M. expansa and M. benedeni in 150 ovine specimens was 132 and 18, respectively. These results show that M. expansa is dominant in goats and sheep, whereas M. benedeni is more common in cattle; PCR can be used for classification of these two species. PMID- 22071023 TI - Evaluation of the bone status in high-level cyclists. AB - The purpose of this study was to evaluate the bone status in highly trained professional cyclists subjected to regular training and tough competitions. Bone mineral density (BMD) was measured at different regions of interest by dual energy X-ray absorptiometry, and main biological parameters related to bone metabolism were obtained in 29 cyclists. Lumbar BMD was 0.94 +/- 0.01g/cm(2) (Z score=-1.28 +/- 0.07), and 1 cyclist out of 4 had an abnormally low value (Z score <-2). The mean Z-score at the total femoral site was -1.22 +/- 0.21, and 45% of athletes had an Z-score of <-2. All femoral neck BMD values were within normal boundaries. The lowest BMD Z-score was measured at the midradius or 1/3 proximal site with a mean Z-score of -1.77 +/- 0.78, but only 3 cyclists (15%) had Z-scores <-2. Biochemical parameters of bone formation (serum osteocalcin and alkaline phosphatase) were normal. Three cyclists had low 25-hydroxyvitamin D levels. Blood testosterone and thyroid stimulating hormone were in the normal range. Insulin-like growth factor 1 levels were in the normal range; however, a significant inverse correlation was found with lumbar BMD (r=0.495; p=0.003). We confirm that cycling has no positive effect on BMD, BMD being often lower than in normal controls at the lumbar site; femoral BMD is less concerned. The absence of beneficial changes at the spine can be explained by biomechanical conditions related to the cyclists' position, reducing loading strains. It is necessary to pay greater attention to the bone status of high-level athletes to prevent an increased risk of fractures. PMID- 22071024 TI - Predictors of bone mineral density testing in patients at high risk of osteoporosis: secondary analyses from the OSTEOPHARM randomized trial. AB - In a randomized trial, we demonstrated that a community pharmacist osteoporosis screening intervention doubled the rates of bone mineral density (BMD) testing in high-risk patients. The purpose of this secondary analysis was to evaluate the potentially modifiable factors associated with BMD testing. From 2005 to 2007, 15 pharmacies randomized 262 patients to intervention (education, pamphlets, point of-care quantitative heel ultrasound [QUS]) or usual care. The main outcome was BMD testing within 4mo. Multivariate regression was used to determine independent correlates of BMD testing. The median age of the cohort was 62yr, 65% were women, and 49% (n=129) were randomized to intervention. Compared with patients who were not tested, those with BMD were more likely to be women (p=0.007) and have excellent or very good health (p<0.001). Postrandomization correlates of BMD test were intervention (p=0.017), greater osteoporosis knowledge (p=0.004), and osteoporosis-specific physician visits (p<0.001). In adjusted analyses, only female sex (adjusted odds ratio [aOR]: 3.0; 95% confidence interval [CI]: 1.3 7.4) and osteoporosis-specific visits (aOR: 3.2; 95% CI: 1.4-7.8) were independently associated with BMD testing. In analyses restricted to intervention patients, abnormal QUS (aOR: 3.7, 95% CI: 1.4-9.1) was the only independent predictor of BMD test. Future interventions should incorporate the finding that osteoporosis-specific visits and abnormal QUS results were strongly associated with getting a BMD testing and should give greater attention to men. PMID- 22071025 TI - Association between vascular calcification and osteoporosis in men with type 2 diabetes. AB - Atherosclerotic vascular disease is common in diabetes, and some data support a link with bone loss. This study evaluates the association between osteoporosis and clinical and metabolic factors and chronic complications of diabetes. We studied 59 diabetic men aged 50-80 yr who were assessed with bone densitometry (dual-energy X-ray absorptiometry). Of them, 10.2% of the patients were found to have osteoporosis in the lumbar spine and 45.8% osteopenia, whereas in the femoral neck, 11.8% had osteoporosis and 49% had osteopenia. There was a significant association of osteoporosis in the lumbar spine L1-L4 (p=0.004) and in the femoral neck (p=0.036) with iliac artery calcification. In addition, there was no association with any other metabolic factors, clinical factors, or chronic complications of diabetes evaluated, except for an association between a previous personal history of fractures (p=0.016) and low bone mineral density in the femoral neck. In conclusion, we found a positive association between the iliac artery calcification and osteoporosis in type 2 diabetic male patients. PMID- 22071026 TI - Hip strength in adults with type 1 diabetes is associated with age at onset of diabetes. AB - We investigated the association of age at onset of type 1 diabetes with areal bone mineral density (aBMD), estimates of bone strength, and outer diameter. Using dual-energy X-ray absorptiometry (DXA), aBMD, axial strength (cross sectional area [CSA]), bending strength (section modulus [SM]), and outer diameter at the narrow neck, intertrochanter, and shaft of the proximal femur were determined for 60 adults. Analysis of covariance (ANCOVA) was used to determine if the DXA-based measures of bone were related to age at onset and if this relationship differed by gender. Age at onset, gender, and the interaction of age at onset by gender were included in the ANCOVA models along with current age, duration, height, lean soft tissue mass, and hemoglobin A1c as covariates. In the adjusted models with CSA, SM, or outer diameter as the dependent variable, age at onset (p<0.01) and gender (p<0.0001) were significant with no interaction. For shaft aBMD, there was a significant age at onset by gender interaction (p=0.0285), where an earlier onset was associated with lower aBMD in the femoral shaft of females but not males. The findings suggest that an earlier onset of type 1 diabetes is associated with lower measures of bone strength and outer diameter. PMID- 22071027 TI - Influence of different DXA acquisition modes on monitoring the changes in bone mineral density after hip resurfacing arthroplasty. AB - Dual-energy X-ray absorptiometry (DXA) is a technique enabling the measurement of bone mineral density (BMD) around prostheses after hip resurfacing arthroplasty (HRA). In this study, we evaluated the consistency of different DXA acquisition modes with 33 patients who had undergone HRA. Patients were scanned with DXA immediately after surgery and at 3-, 6-, and 12-mo time points. All the patients were scanned with dual femur and orthopedic hip acquisition modes and analyzed using 10-region ROI model. With both acquisition modes, a statistically significant decrease (p<0.05, Wilcoxon's test) in BMD at 3mo was revealed in 3 ROIs, located to upper and lateral upper femur. Both acquisition modes detected similarly (p<0.01) preservation of the femoral bone stock within 12mo in all but 1 ROI. The applied acquisition protocols involved the use of different footplates for hip fixation. Because the differences between acquisition modes ranged between +1.6% and -7.1% and the reproducibility of BMD values can vary by as much as 28% due to hip rotation, it is proposed that both dual femur and orthopedic hip acquisition modes can be used to monitor the changes in BMD after HRA. However, the same hip rotation is recommended for all DXA measurements. PMID- 22071028 TI - Validation of diagnostic codes for subtrochanteric, diaphyseal, and atypical femoral fractures using administrative claims data. AB - Administrative claims databases have large samples and high generalizability. They have been used to evaluate associations of atypical femoral fractures with bisphosphonates. We developed and assessed accuracy of claims-based algorithms with hospital and physician diagnosis codes for these fractures. Medical records and radiology reports of all adults admitted at University of Alabama at Birmingham Health System from 2004 to 2008 with International Classification of Diseases, Ninth Revision hospital discharges and surgeons' fracture repair codes for subtrochanteric femoral fractures and random sample of other femoral fractures were reviewed. We identified 137 persons with suspected subtrochanteric femoral fractures and randomly selected 50 persons with either suspected diaphyseal femoral fractures or hip fractures other than subtrochanteric and diaphyseal femoral fractures (typical hip fractures). Eleven patients had radiographic features indicative of atypical femoral fractures. The positive predictive value (PPV) of claims-based algorithms varied with primary or secondary positions on discharge diagnoses and the sources of diagnosis codes. The PPV for fractures ranged 69-89% for subtrochanteric femoral, 89-98% for diaphyseal femoral, and 85-98% for typical hip fractures. The PPV of administrative codes for defining a femoral fracture as atypical was low and imprecise. Claims-based algorithms combining hospital discharges with surgeon's diagnosis codes had high PPV to identify the site of subtrochanteric or diaphyseal femoral fractures vs typical hip fractures. However, claims-based data were not accurate in identifying atypical femoral fractures. These claims algorithms will be useful in future population-based observational studies to evaluate associations between osteoporosis medications and subtrochanteric and diaphyseal femoral fractures. PMID- 22071029 TI - BMD measurement and precision: a comparison of GE Lunar Prodigy and iDXA densitometers. AB - This study assessed bone mineral density (BMD) comparability and precision using Lunar Prodigy and iDXA densitometers (GE Healthcare, Madison, WI) in adults. Additionally, the utility of supine forearm measurement with iDXA was investigated. Lumbar spine and bilateral proximal femur measurements were obtained in routine clinical manner in 345 volunteers, 202 women and 143 men of mean age 52.5 (range: 20.1-91.6)yr. Seated and supine distal forearm scans were obtained in a subset (n=50). Lumbar spine and proximal femur precision assessments were performed on each instrument following International Society for Clinical Densitometry recommendations in 30 postmenopausal women. BMD at the L1 L4 spine, total proximal femur, and femoral neck was very highly correlated (r(2)>=0.98) between densitometers, as was the one-third radius site (r(2)=0.96). Bland-Altman analyses demonstrated no clinically significant bias at all evaluated sites. BMD precision was similar between instruments at the L1-L4 spine, mean total proximal femur, and femoral neck. Finally, one-third radius BMD measurements in the supine vs seated position on the iDXA were highly correlated (r(2)=0.96). In conclusion, there is excellent BMD correlation between iDXA and Prodigy densitometers. Similarly, BMD precision is comparable with these two instruments. PMID- 22071030 TI - Impact of a new sarco-osteopenia definition on health-related quality of life in a population-based cohort in Northern Europe. AB - Sarcopenia has been shown to be a marker of falling; therefore, combining osteopenia and sarcopenia could identify a frailer, higher-fracture-risk population. We aimed to define sarco-osteopenia (SOP) in a population-based healthy young sample using both muscle functional and quantitative parameters and assessing the impact of this definition on health-related quality of life. A population sample of 304 patients aged 25-70 yr was analyzed with a Lunar DPX-IQ dual-energy X-ray absorptiometry machine (GE Healthcare, Pollards Wood, UK), and their health-related quality of life was assessed with the Short-Form-36 (SF-36) questionnaire. SOP was defined as bone mineral density (BMD) -1 standard deviation (SD) and height-adjusted appendicular muscle mass -2 SD and/or grip strength -2 SD less than the mean values of 77 young individuals in the population sample (age: 25-39 yr). Our proposed SOP definition identifies 3-9% of the population older than 40 yr as sarco-osteopenic. These individuals also show markedly lower scores in the role-physical (p=0.01), vitality (p=0.03), and role emotional (p=0.02) subscales of the SF-36 questionnaire. No difference in the quality of life was observed between osteopenic individuals and those with normal BMD. The new definition identifies a population with significant decrements in health-related quality of life. PMID- 22071032 TI - Morphometric endoscopic study of the pharynx in patients with sleep apnea. AB - PURPOSE: The aims of the study were to measure endoscopically the retrolingual pharynx during wakefulness and sleep before and after maxillomandibular advancement surgery and to quantify the changes observed. MATERIALS AND METHODS: Eighteen patients with mild to severe grade obstructive sleep apnea hypopnea were evaluated during wakefulness while sitting and lying down and during induced sleep in dorsal decubitus while breathing naturally. Images of the retrolingual region of the pharynx were captured with a nasofibroscope and recorded on a DVD using the Sony Vegas 8.0 software (Sony Creative Software, Madison, WI). The images captured in greater and smaller aperture were measured with the Image J software (produced by Wayne Rasband, United States National Institutes of Health, Bethesda, MD) in linear anteroposterior and linear laterolateral areas. A correction factor was then applied to equalize the size of the images and thus compare them to one another. RESULTS: The postoperative dimensions of the pharynx always increased significantly in all measurements compared with the preoperative ones. During induced sleep in dorsal decubitus, there was a greater gain in the area of smaller aperture (201.33%). CONCLUSIONS: The proposed method showed that the dimensions of the pharynx always increased significantly after surgery for maxillomandibular advancement, although the gain was not homogeneous in all dimensions and also varied according to state of consciousness. The greatest gain was observed in the area of smaller aperture with the patient in induced sleep, thus reducing the collapse of the pharynx. PMID- 22071031 TI - Genetic diversity of influenza A(H1N1)2009 virus circulating during the season 2010-2011 in Spain. AB - BACKGROUND: Genetic diversity of influenza A(H1N1)2009 viruses has been reported since the pandemic virus emerged in April 2009. Different genetic clades have been identified and defined based on amino acid substitutions found in the haemagglutinin (HA) protein sequences. In Spain, circulating influenza viruses are monitored each season by the regional laboratories enrolled in the Spanish Influenza Surveillance System (SISS). The analysis of the HA gene sequence helps to detect the genetic diversity and viral evolution. OBJECTIVES: To perform an analysis of the genetic diversity of influenza A(H1N1)2009 viruses circulating in Spain during the season 2010-2011 based on analysis of the HA sequence gene. STUDY DESIGN: Phylogenetic analysis based on the HA1 subunit of the haemagglutinin gene was carried out on 220 influenza A(H1N1)2009 viruses circulating during the season 2010-2011. RESULTS: Six different genetic groups were identified among circulating A(H1N1)2009 viruses, five of them were previously reported during season 2010-2011. A new group, characterized by E172K and K308E changes and a proline at position 83, was observed in 12.27% of the Spanish viruses. CONCLUSION: Co-circulation of six different genetic groups of influenza A(H1N1)2009 viruses was identified in Spain during the season 2010 2011. Nevertheless, at this stage, none of the groups identified to date have resulted in significant antigenic changes according to data collected by World Health Organization Collaborating Centres for influenza surveillance. PMID- 22071033 TI - Clinical manifestations and prognosis of patients with Ramsay Hunt syndrome. AB - PURPOSE: Patients with Ramsay Hunt syndrome have a poorer prognosis than those with Bell palsy despite the use of various treatment modalities. We compared the clinical characteristics, treatment methods, and outcomes in patients with Ramsay Hunt syndrome and Bell palsy. MATERIALS AND METHODS: Patients with Ramsay Hunt syndrome were compared with patients with Bell palsy treated using oral steroids and with those treated with both steroids and an antiviral agent. Functional recovery of the facial nerve was scored according to the House-Brackmann grading system. Patients were followed up until recovery or for 3 months. Recovery rates in each group were assessed by age, sex, and initial and last House-Brackmann grade. RESULTS: Compared with patients with Bell palsy, those with Ramsay Hunt syndrome were generally younger, had initially more severe facial palsy, and a lower recovery rate. Various factors including initial House-Brackmann grade, starting time to treatment, age, comorbid disease, electroneurography, and electromyography showed some correlations with prognosis in all groups. The addition of antiviral agents to an oral steroid regimen did not improve the recovery rate of patients with Bell palsy. CONCLUSION: Patients with Ramsay Hunt syndrome have a poorer prognosis than do those with Bell palsy. PMID- 22071034 TI - Climate change and health: indoor heat exposure in vulnerable populations. AB - INTRODUCTION: Climate change is increasing the frequency of heat waves and hot weather in many urban environments. Older people are more vulnerable to heat exposure but spend most of their time indoors. Few published studies have addressed indoor heat exposure in residences occupied by an elderly population. The purpose of this study is to explore the relationship between outdoor and indoor temperatures in homes occupied by the elderly and determine other predictors of indoor temperature. MATERIALS AND METHODS: We collected hourly indoor temperature measurements of 30 different homes; outdoor temperature, dewpoint temperature, and solar radiation data during summer 2009 in Detroit, MI. We used mixed linear regression to model indoor temperatures' responsiveness to weather, housing and environmental characteristics, and evaluated our ability to predict indoor heat exposures based on outdoor conditions. RESULTS: Average maximum indoor temperature for all locations was 34.85 degrees C, 13.8 degrees C higher than average maximum outdoor temperature. Indoor temperatures of single family homes constructed of vinyl paneling or wood siding were more sensitive than brick homes to outdoor temperature changes and internal heat gains. Outdoor temperature, solar radiation, and dewpoint temperature predicted 38% of the variability of indoor temperatures. CONCLUSIONS: Indoor exposures to heat in Detroit exceed the comfort range among elderly occupants, and can be predicted using outdoor temperatures, characteristics of the housing stock and surroundings to improve heat exposure assessment for epidemiological investigations. Weatherizing homes and modifying home surroundings could mitigate indoor heat exposure among the elderly. PMID- 22071035 TI - Acute air pollution effects on heart rate variability are modified by SNPs involved in cardiac rhythm in individuals with diabetes or impaired glucose tolerance. AB - BACKGROUND: Epidemiological studies have shown associations between particulate matter (PM) and heart rate variability (HRV). OBJECTIVES: We investigated the effects of air pollution on the root mean square of successive differences (RMSSD) and the standard deviation of normal-to-normal intervals (SDNN) and effect modifications by single nucleotide polymorphisms (SNP). METHODS: Between March 2007 and December 2008 207 ECG recordings comprising 1153 1 h-intervals were measured in 61 individuals with type 2 diabetes or impaired glucose tolerance (IGT) from Augsburg, Germany. Associations between 1 h-averages of air pollutants (PM, sulphate, black carbon, and ultrafine particles) and ECG parameters were analyzed using additive mixed models. Genotypes of 139 SNPs supposed to be involved in cardiac rhythm were identified in the literature. Using regression trees for longitudinal data, SNPs associated with ECG parameters were determined and included as potential air pollution effect modifiers. RESULTS: We observed concurrent and lagged decreases in SDNN by about 2-5% in association with all air pollutants, especially in participants with at least one minor allele of rs332229. Increases in PM<2.5 MUm (PM(2.5)) were associated with 4 h-lagged decreases of -6.6% [95%-confidence interval:-10.6;-2.6%] and -13.0% [ 20.7;-5.1%] in SDNN in individuals with one or two minor alleles. We observed a 7.2% [-12.2;-1.8%] reduction in RMSSD associated with concurrent increases in PM(2.5.) Individuals with at least one minor allele of rs2096767 or at most one minor allele of rs2745967 exhibited stronger PM(2.5) effects. CONCLUSIONS: We identified a genetic predisposition in persons with diabetes or IGT making them potentially more susceptible to air pollutants with regard to changes in HRV. PMID- 22071037 TI - An unusual cause of myocardial ischaemia. PMID- 22071036 TI - Pre-implantation psychological functioning preserved in majority of implantable cardioverter defibrillator patients 12 months post implantation. AB - BACKGROUND: The impact of ICD therapy on patient well being has typically focused on mean differences between groups, thereby neglecting changes within individuals. Using an intra-individual approach, we examined (i) the prevalence of implantable cardioverter defibrillator (ICD) patients maintaining their pre implantation level of psychological functioning at 12 months, and (ii) factors associated with deterioration in functioning. METHODS: Consecutively implanted ICD patients (n=332) completed a set of standardized and validated patient reported measures at baseline and at 12 months post implantation. RESULTS: The majority of patients (72.8% to 81.7%) preserved their pre implantation level of psychological functioning 12 months post implantation. In adjusted analysis, ICD shock (all ps<.001) and Type D personality (all ps<.05) were independent predictors of deterioration in psychological functioning at 12 months across all domains, while baseline psychological status was associated with an improvement (all ps<.05). Patients with a primary prevention indication experienced a decrease in ICD concerns (p=.03) and anxiety (p=.006), and older patients (p=.04) a decrease in anxiety symptoms during the follow-up period. By contrast, patients with left ventricular dysfunction (p=.007) and atrial fibrillation (p=.02) were more likely to experience an increase in anxiety. CONCLUSIONS: The majority of ICD patients maintained their pre implantation level of psychological functioning at 12 months. A subset of patients was at risk of poor psychological adaptation, attributable to ICD shocks, Type D personality, atrial fibrillation, and left ventricular dysfunction, while primary prevention indication and older age had a protective effect against deterioration in functioning. PMID- 22071038 TI - Might diabetes-related increased iron stores erase the female advantage in the development of coronary heart disease? PMID- 22071039 TI - Layer-specific strain-encoded MRI for the evaluation of left ventricular function and infarct transmurality in patients with chronic coronary artery disease. AB - BACKGROUND: The study aimed to evaluate whether layer-specific myocardial deformation imaging performed by strain-encoded imaging (SENC) allows quantification of regional left ventricular function and is related to scar transmurality defined by contrast-enhanced magnetic resonance imaging (ceMRI) in patients with chronic coronary artery disease (CAD). METHODS: 50 patients (mean age 62 +/- 10 years) with CAD underwent ceMRI. Regional myocardial function was evaluated semi-quantitatively from steady-state free-precession cine sequences. Layer-specific peak circumferential strain was measured from long-axis views and peak longitudinal strain was evaluated from short-axis views in a 16-segment model. The extent of myocardial infarction was determined semiautomatically for each segment as relative amount of hyperenhancement by ceMRI. Wall motion and the degree of hyperenhancement were related to layer-specific myocardial strain. RESULTS: A total of 589 of 600 segments (98%) were analysed. Endocardial and epicardial circumferential as well as longitudinal strain showed significant differences between visually defined segmental function states and differed also significantly between the degree of infarct transmurality (all p<0.001). A cutoff peak circumferential endocardial strain value of -15% differentiated nontransmural from transmural infarcted myocardium with a sensitivity of 100% and a specificity of 86% (area under the curve (AUC) 0.94). Distinction of nontransmural infarcted myocardium from transmural infarcted myocardium was done more accurately using circumferential endocardial strain compared to longitudinal endocardial strain (AUC 0.94 vs. AUC 0.76, p=0.003). CONCLUSIONS: Quantitative analysis of segmental deformation by layer-specific SENC allows accurate discrimination between different transmurality states of myocardial infarction in patients with chronic CAD. Circumferential endocardial strain showed the best distinction between the different degrees of infarct transmurality. PMID- 22071040 TI - Metallic taste after coronary artery stent implantation. PMID- 22071041 TI - Keshan to Kansas. PMID- 22071042 TI - Patients admitted to hospital with chest pain--changes in a 20-year perspective. AB - OBJECTIVES: To describe the differences in characteristics and outcome between two consecutive series of patients admitted to hospital with chest pain in a 20 year perspective. Particular emphasis is placed on changes in outcome in relation to the initial electrocardiogram (ECG). SUBJECTS: In the two periods, 1986-1987 and 2008, all patients with chest pain admitted to the study hospitals in Gothenburg, Sweden, were included. RESULTS: Five thousand and sixteen patients were registered in a period of 21 months in 1986-1987 and 2287 patients were registered during 3 months in 2008. In a comparison of the two time periods, the age of chest pain patients was not significantly different (mean age 60.1 +/- 17.8 years in 1986-1987 and 59.8 +/- 19.1 years in 2008, p=0.50). There was a lower prevalence of previous angina pectoris, congestive heart failure and current smoking in the second period, whereas a history of acute myocardial infarction, hypertension and diabetes mellitus had become more prevalent. The use of cardio-protective drugs increased and ECG changes indicating acute myocardial ischemia on admission to hospital decreased. Length of hospitalisation was reduced from a median of 5 days to 3 days (p<0.0001). A significant decrease in 30-day and 1-year mortality was found (3.8% in 1986-1987 vs 2.0% in 2008 and 9.9% vs 6.3% respectively, p<0.0001 for both comparisons). CONCLUSIONS: During a period of 20 years, the characteristics and outcome of patients admitted to hospital with chest pain changed. The most important changes were a lower prevalence of ECG signs indicating acute myocardial ischemia on admission, shorter hospitalisation time and a lower 30-day and 1-year mortality. PMID- 22071043 TI - Commotio cordis as a result of neutralization shot with the Flash Ball less lethal weapon. PMID- 22071047 TI - How to develop an effective obstetric checklist. AB - Checklists to guide critical procedures are becoming an increasingly important part of medical practice. These tools have proved effective in improving outcome in a variety of medical settings, including obstetrics. In this review, we outline essential principles of successful checklist creation and implementation and review our experience with checklist development in a worldwide, multi institutional health care delivery system. PMID- 22071049 TI - Evaluation and management of severe preeclampsia before 34 weeks' gestation. AB - OBJECTIVE: We sought to review the risks and benefits of expectant management of severe preeclampsia remote from term, and to provide recommendations for expectant management, maternal and fetal evaluation, treatment, and indications for delivery. METHODS: Studies were identified through a search of the MEDLINE database for relevant peer-reviewed articles published in the English language from January 1980 through December 2010. Additionally, the Cochrane Library, guidelines by organizations, and studies identified through review of the above documents and review articles were utilized to identify relevant articles. Where reliable data were not available, opinions of respected authorities were used. RESULTS AND RECOMMENDATIONS: Published randomized trials and observational studies regarding management of severe preeclampsia occurring <34 weeks of gestation suggest that expectant management of selected patients can improve neonatal outcomes but that delivery is often required for worsening maternal or fetal condition. Patients who are not candidates for expectant management include women with eclampsia, pulmonary edema, disseminated intravascular coagulation, renal insufficiency, abruptio placentae, abnormal fetal testing, HELLP syndrome, or persistent symptoms of severe preeclampsia. For women with severe preeclampsia before the limit of viability, expectant management has been associated with frequent maternal morbidity with minimal or no benefits to the newborn. Expectant management of a select group of women with severe preeclampsia occurring <34 weeks' gestation may improve newborn outcomes but requires careful in-hospital maternal and fetal surveillance. PMID- 22071051 TI - Improved performance of maternal-fetal medicine staff after maternal cardiac arrest simulation-based training. AB - OBJECTIVE: To determine the impact of simulation-based maternal cardiac arrest training on performance, knowledge, and confidence among Maternal-Fetal Medicine staff. STUDY DESIGN: Maternal-Fetal Medicine staff (n = 19) participated in a maternal arrest simulation program. Based on evaluation of performance during initial simulations, an intervention was designed including: basic life support course, advanced cardiac life support pregnancy modification lecture, and simulation practice. Postintervention evaluative simulations were performed. All simulations included a knowledge test, confidence survey, and debriefing. A checklist with 9 pregnancy modification (maternal) and 16 critical care (25 total) tasks was used for scoring. RESULTS: Postintervention scores reflected statistically significant improvement. Maternal-Fetal Medicine staff demonstrated statistically significant improvement in timely initiation of cardiopulmonary resuscitation (120 vs 32 seconds, P = .042) and cesarean delivery (240 vs 159 seconds, P = .017). CONCLUSION: Prompt cardiopulmonary resuscitation initiation and pregnancy modifications application are critical in maternal and fetal survival during cardiac arrest. Simulation is a useful tool for Maternal-Fetal Medicine staff to improve skills, knowledge, and confidence in the management of this catastrophic event. PMID- 22071052 TI - Perinatal outcome in pregnancies complicated by isolated oligohydramnios diagnosed before 37 weeks of gestation. AB - OBJECTIVE: To analyze pregnancy outcome in cases of isolated oligohydramnios at preterm. METHODS: A retrospective cohort study of singleton pregnancies diagnosed with isolated oligohydramnios at preterm (n = 108). Pregnancy outcome was compared with a matched control group of low-risk preterm pregnancies with normal levels of amniotic fluid in a 3:1 ratio (n = 324). RESULTS: Pregnancies complicated by isolated oligohydramnios were characterized by a higher rate of preterm deliveries (26.9% vs 12.3%, P < .001), most of which were iatrogenic, and a higher rate of labor induction and cesarean delivery. Neonates with isolated oligohydramnios were characterized by a lower birthweight and a higher rate of neonatal morbidity. These differences were eliminated when the analysis was limited to the subgroup of pregnancies with isolated oligohydramnios that were managed expectantly and delivered spontaneously at term. CONCLUSION: Adverse pregnancy outcome in cases of isolated oligohydramnios diagnosed at <37 weeks appears to be related to a considerable degree to iatrogenic prematurity. PMID- 22071048 TI - Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis. AB - The purpose of this study was to determine whether the administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation reduces the risk of preterm birth and late miscarriage. We conducted a systematic review and metaanalysis of randomized controlled trials of the early administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation. Five trials that comprised 2346 women were included. Clindamycin that was administered at <22 weeks of gestation was associated with a significantly reduced risk of preterm birth at <37 weeks of gestation and late miscarriage. There were no overall differences in the risk of preterm birth at <33 weeks of gestation, low birthweight, very low birthweight, admission to neonatal intensive care unit, stillbirth, peripartum infection, and adverse effects. Clindamycin in early pregnancy in women with abnormal vaginal flora reduces the risk of spontaneous preterm birth at <37 weeks of gestation and late miscarriage. There is evidence to justify further randomized controlled trials of clindamycin for the prevention of preterm birth. However, a deeper understanding of the vaginal microbiome, mucosal immunity, and the biology of BV will be needed to inform the design of such trials. PMID- 22071053 TI - National Diabetes Data Group vs Carpenter-Coustan criteria to diagnose gestational diabetes. AB - OBJECTIVE: The objective of the study was to compare perinatal outcomes among women diagnosed with gestational diabetes by the National Diabetes Data Group (NDDG) criteria with women meeting only Carpenter-Coustan criteria. STUDY DESIGN: This was a 14 year retrospective cohort. Women who screened positive with 1 hour glucose load 140 mg/dL or greater underwent a diagnostic 3 hour oral glucose tolerance test. We report adjusted prevalence ratios (aPRs) of perinatal outcome risk. RESULTS: Of the 4659 screen-positive women with diagnostic testing, 1082 (3.3%, of 33,179) met NDDG criteria; 1542 (4.6%, of 33,179), or 460 more, met Carpenter-Coustan criteria. These 460 untreated women had greater risk of preeclampsia than women diagnosed by NDDG criteria (aPR, 1.70; 95% confidence interval [CI], 1.23-2.35). They had a greater risk of cesarean delivery (aPR, 1.16; 95% CI, 1.04-1.30) and infants greater than 4000 g (aPR, 1.25; 95% CI, 1.01 1.56) than women not meeting either diagnostic criteria. CONCLUSION: The 42.5% additional women diagnosed only by Carpenter-Coustan criteria are at greater risk for some adverse outcomes. Cost-effectiveness of a change remains to be determined. PMID- 22071054 TI - Ultrasound assessment of intrauterine growth restriction: relationship to neonatal body composition. AB - OBJECTIVE: The objective of the study was to compare prenatal ultrasound parameters for intrauterine growth restriction (IUGR) with newborn percent body fat (%BF). STUDY DESIGN: This was a prospective study of 87 pregnancies followed with ultrasound. Subjects were categorized into 3 groups: estimated fetal weight (EFW) less than the 10th percentile, abdominal circumference (AC) less than the fifth percentile, and normal biometry. Neonatal %BF by air displacement plethysmography was compared between each group using multivariable analyses. RESULTS: The %BF in the EFW less than the 10th percentile group (5.1 +/- 2.9%) was significantly lower than either AC less than the fifth percentile (9.5 +/- 3.3%) or normal groups (11.6 +/- 5.6%). EFW less than the 10th percentile best predicted %BF by regression model. Neonatal morbidity was not significantly higher in the EFW less than the 10th percentile group. CONCLUSION: Newborn %BF was significantly lower in infants with EFW less than the 10th percentile compared with AC less than the fifth percentile, an intermediate finding. An AC less than the fifth percentile on ultrasound does not reflect the same severity of IUGR as EFW less than the 10th percentile. PMID- 22071055 TI - Effect of gestational weight gain on perinatal outcomes in women with type 2 diabetes mellitus using the 2009 Institute of Medicine guidelines. AB - OBJECTIVE: We sought to examine associations between gestational weight gain according to the 2009 Institute of Medicine (IOM) guidelines and perinatal outcomes in overweight/obese women with type 2 diabetes mellitus (T2DM). STUDY DESIGN: This is a retrospective cohort study of 2310 women with T2DM enrolled in the California Diabetes and Pregnancy Program. Gestational weight gain was categorized by 2009 IOM guidelines. Perinatal outcomes were assessed using the chi(2) test and multivariable logistic regression analysis. RESULTS: With excessive gestational weight gain, the odds of having large-for-gestational age (adjusted odds ratio [aOR], 2.00; 95% confidence interval [CI], 1.33-3.00) or macrosomic (aOR, 2.59; 95% CI, 1.56-4.30) neonates and cesarean delivery (aOR, 1.47; 95% CI, 1.03-2.10) was higher. Women with excessive gestational weight gain per week had increased odds of preterm delivery (aOR, 1.57; 95% CI, 1.11-2.20). CONCLUSION: In overweight or obese women with T2DM, gestational weight gain greater than the revised IOM guidelines was associated with higher odds of perinatal morbidity, suggesting these guidelines are applicable to a diabetic population. PMID- 22071056 TI - Obstetrical and perinatal outcomes among women with gestational hypertension, mild preeclampsia, and mild chronic hypertension. AB - OBJECTIVE: The purpose of this study was to compare maternal and neonatal outcomes of women with gestational hypertension (GHTN), mild chronic hypertension (CHTN), and mild preeclampsia at delivery. STUDY DESIGN: A multicenter database that contained 228,668 deliveries was used to extract data on gravid women with GHTN, preeclampsia, and CHTN and on women without hypertensive disease (control group). Univariate and multivariate logistic regression analyses were performed. RESULTS: There were 4918 women with GHTN, 5274 women with preeclampsia, 2531 women with CHTN, and 15,221 control subjects. Women with GHTN had the greatest risk for blood transfusion (adjusted odds ratio [aOR], 4.6; 95% confidence interval [CI], 3.4-6.3), intensive care unit admission (aOR, 25.7; 95% CI, 9.8 67.3), and lowest risk for stillbirth (aOR, 0.1; 95% CI, 0.04-0.4); women with preeclampsia had the greatest risk for postpartum hypertension (aOR, 9.6; 95% CI, 7.2-12.9). Neonates with GHTN had the greatest risk for ventilator requirements (aOR, 7.5; 95% CI, 4.6-12.4). CONCLUSION: Women with gestational hypertension and their neonates had significant risks for morbidity, compared with women with mild chronic hypertension and those with mild preeclampsia. PMID- 22071057 TI - Impact of multiple cesarean deliveries on maternal morbidity: a systematic review. AB - OBJECTIVE: The purpose of this study was to determine the impact of increasing numbers of cesarean deliveries on maternal morbidity. This study was performed for the 2010 National Institutes of Health Consensus Development Conference on Vaginal Birth After Cesarean: New Insights. STUDY DESIGN: We conducted a systematic review and metaanalysis of observational studies. RESULTS: Twenty-one studies (2,282,922 deliveries) were included. The rate of hysterectomy, blood transfusions, adhesions, and surgical injury all increased with increasing number of cesarean deliveries. The incidence of placenta previa increased from 10/1000 deliveries with 1 previous cesarean delivery to 28/1000 with >=3 cesarean deliveries. Compared with women with previa and no previous cesarean delivery, women with previa and >=3 cesarean deliveries had a statistically significant increased risk of accreta (3.3-4% vs 50-67%), hysterectomy (0.7-4% vs 50-67%), and composite maternal morbidity (15% vs 83%; odds ratio, 33.6; 95% confidence interval, 14.6-77.4). CONCLUSION: Serious maternal morbidity progressively increased as the number of previous cesarean deliveries increased. PMID- 22071058 TI - Molecular phenotype of monocytes at the maternal-fetal interface. AB - OBJECTIVE: The purpose of this study was to gain insight into the pathways that are associated with inflammation at the maternal-fetal interface. This study examined the molecular characteristics of monocytes that were derived from the maternal circulation and the placenta of obese women. STUDY DESIGN: Mononuclear cells were isolated from placenta, venous maternal, and umbilical cord blood at term delivery; activated monocytes were separated with CD14 immunoselection. The genotype and expression pattern of the monocytes were analyzed by microarray and real-time reverse transcriptase-polymerase chain reaction. RESULTS: The transcriptome of the maternal blood and placental CD14 monocytes exhibited 73% homology, with 10% (1800 common genes) differentially expressed. Genes for immune sensing and regulation, matrix remodeling, and lipid metabolism were enhanced 2 2006 fold in placenta, compared with maternal monocytes. The CD14 placental monocytes exhibited a maternal genotype (9% DYS14 expression) as opposed to the fetal genotype (90% DYS14 expression) of the trophoblast cells. CONCLUSION: CD14 monocytes from the maternal blood and the placenta share strong phenotypic and genotypic similarities with an enhanced inflammatory pattern in the placenta. The functional traits of the CD14 blood and placental monocytes suggest that they both contribute to propagation of inflammation at the maternal-fetal interface. PMID- 22071059 TI - Supplemental oxygen for the prevention of postcesarean infectious morbidity: a randomized controlled trial. AB - OBJECTIVE: The purpose of this study was to investigate whether supplemental oxygen during and for 2 hours after cesarean delivery reduces the incidence of postcesarean infectious morbidity. STUDY DESIGN: We conducted a randomized, controlled trial from 2008-2010. Women who underwent cesarean delivery were randomly assigned to receive either 2 L of oxygen by nasal cannula during cesarean delivery only (standard care) or 10 L of oxygen by nonrebreather mask (intervention group) during and for 2 hours after cesarean delivery. Women who underwent scheduled or intrapartum cesarean delivery were eligible and were observed for 1 month after the procedure. The primary composite outcome was maternal infectious morbidity, which included endometritis and wound infection. RESULTS: Five hundred eighty-five women were included in the final analysis. Infectious morbidity occurred in 8.8% of patients in the standard care group and in 12.2% of patients in the supplemental oxygen group. There was no significant difference in the rate of infectious morbidity between the standard care and intervention groups (relative risk, 1.4; 95% confidence interval, 0.9-2.3). CONCLUSION: Supplemental oxygen does not reduce the rate of postcesarean delivery infectious morbidity, including endometritis and wound infection. PMID- 22071060 TI - 17-alphahydroxyprogesterone caproate in women with previous spontaneous preterm delivery: does a previous term delivery affect the rate of recurrence? AB - OBJECTIVE: The purpose of this study was to determine the role of previous term delivery on the rate of recurrent preterm birth in women with previous spontaneous preterm delivery (SPTD) who receive 17-alphahydroxyprogesterone caproate (17P) therapy. STUDY DESIGN: Women with singleton gestations who were receiving 17P therapy were studied. Rates of recurrent SPTD were compared for 1 or >=2 SPTD with and without a previous term delivery. RESULTS: Five thousand one hundred two women had 1 previous SPTD, and 2217 women had >=2 SPTDs. In women with 1 previous SPTD, a previous term delivery had lower rates of SPTD at <35 weeks (8.4% vs 11.2%; P = .002) and preterm delivery at <32 weeks (4.7% vs 6.2%; P = .027) compared with those women with no such history. No differences were found for SPTD at <35 weeks with >=2 SPTDs. CONCLUSION: In patients who received 17P therapy with 1 previous SPTD, a previous term delivery confers a reduction in risk of preterm delivery at <37, <35, and <32 weeks' gestation; such reduction is not evident with >=2 previous SPTDs. PMID- 22071061 TI - Obstetric outcomes and maternal satisfaction in nulliparous women using patient controlled epidural analgesia. AB - OBJECTIVE: The purpose of this study was to compare obstetric outcomes and maternal satisfaction in nulliparous women in spontaneous labor who used patient controlled epidural analgesia (PCEA) vs continuous epidural infusion (CEI). STUDY DESIGN: We conducted a double-masked trial of 270 nulliparous women who were assigned randomly to 3 groups (with a concentration 0.1% bupivacaine and 2 MUg/mL fentanyl): group I, CEI-only (10 mL/h); group II, CEI + PCEA (CEI 10 mL/h plus PCEA 10 mL, at 20 minutes); group III, PCEA-only (10 mL, at 20 minutes). A PCEA bolus button was given to each subject. The primary outcome was the dosage of local anesthetic that was used. RESULTS: The total milligrams of bupivacaine that were used was less in the PCEA-only group compared with CEI: group I. 74.8 +/- 36 mg; group II, 97.3 +/- 53 mg; group III, 52.4 +/- 42 mg (P < .001). Pain with pushing, however, was worse in the PCEA-only group. Median satisfaction scores were similar (scale, 0 [best] to 100 [worst]: group I, 0; group II, 0; group III, 0 (P = .23). CONCLUSION: PCEA results in less anesthetic used, and maternal satisfaction remains high without a continuous infusion. Pain with pushing, however, was worse with the PCEA alone. PMID- 22071062 TI - Pregnancy outcomes in women who have undergone an atrial switch repair for congenital d-transposition of the great arteries. AB - OBJECTIVE: Women who underwent an atrial switch procedure (Senning or Mustard) for repair of d-transposition of the great arteries (d-TGA) are now of reproductive age. We sought to assess their ability for a successful pregnancy. STUDY DESIGN: Clinical data were reviewed for all women of reproductive age who carried a diagnosis of d-TGA and atrial switch procedure who were observed at 2 tertiary care centers over 10 years. RESULTS: Among 25 women who were identified, there were 21 pregnancies that resulted in 14 live births. The preterm birth rate was 50%. Pregnancy complications occurred in 5 women. There were no deaths. Serial echocardiographic data demonstrated a fall in right ventricular function during pregnancy, with some improvement postpartum. Intracardiac baffle obstruction that required postpartum stenting occurred in 36% of the completed pregnancies. CONCLUSION: Women who have undergone an atrial switch procedure for d-TGA have high rates of pregnancy and cardiac complications and should be counseled accordingly. PMID- 22071063 TI - Influence of gestational age and reason for prior preterm birth on rates of recurrent preterm delivery. AB - OBJECTIVE: We sought to compare rates of recurrent spontaneous preterm birth (SPTB) in women receiving 17-alpha-hydroxyprogesterone caproate (17P) with prior SPTB due to preterm labor (PTL) vs preterm premature rupture of membranes (PPROM). STUDY DESIGN: Women with singleton gestation having 1 prior SPTB enrolled at 16-24.9 weeks' gestation for weekly outpatient 17P administration were identified from a database. Rates of recurrent SPTB were compared between those with prior SPTB due to PTL or PPROM overall and by gestational age at prior SPTB. RESULTS: Records from 2123 women were analyzed. The prior PTL group vs the prior PPROM group experienced higher rates of recurrent SPTB at <37 weeks (29.7% vs 22.9%, P = .004), <35 weeks (14.0% vs 9.1%, P = .004), and <32 weeks (5.9% vs 3.3%, P = .024), respectively. CONCLUSION: Reason and gestational age of prior SPTB influence the likelihood of recurrent SPTB in women receiving 17P prophylaxis. PMID- 22071064 TI - Homing of placenta-derived mesenchymal stem cells after perinatal intracerebral transplantation in a rat model. AB - OBJECTIVE: The aim of this study is to assess early homing of placenta-derived stem cells after perinatal intracerebral transplantation in rats. STUDY DESIGN: Neonatal Wistar rats (2-4 days old) were anesthetized, and 250,000 human placenta derived mesenchymal stem cells (MSC) injected into the lateral ventricle or the paraventricular white matter using a stereotactic frame. Donor MSC were detected by immunohistochemistry using an antihuman HLA-ABC antibody. RESULTS: In all, 84% of the animals survived the transplantation. Donor cells were detected in the brain ventricle 1-2 hours posttransplantation. After 4 hours, donor cells migrated throughout the ventricular system. At 1-4 weeks after transplantation, some cells had migrated into the periventricular white matter. CONCLUSION: Human placenta-derived MSC were successfully transplanted into the lateral ventricles of neonatal rats. Donor cells survived, homed, and migrated in the recipient brains. Proliferation and differentiation analysis and functional tests will assess the therapeutic effects of stem cell transplantation. PMID- 22071065 TI - Treating mild gestational diabetes mellitus: a cost-effectiveness analysis. AB - OBJECTIVE: This study investigated the cost-effectiveness of treating mild gestational diabetes mellitus (GDM). STUDY DESIGN: A decision analytic model was built to compare treating vs not treating mild GDM. The primary outcome was the incremental cost per quality-adjusted life year (QALY). All probabilities, costs, and benefits were derived from the literature. Base case, sensitivity analyses, and a Monte Carlo simulation were performed. RESULTS: Treating mild GDM was more expensive, more effective, and cost-effective at $20,412 per QALY. Treatment remained cost-effective when the incremental cost to treat GDM was less than $3555 or if treatment met at least 49% of its reported efficacy at the baseline cost to treat of $1786. CONCLUSION: Treating mild GDM is cost-effective in terms of improving maternal and neonatal outcomes including decreased rates of preeclampsia, cesarean sections, macrosomia, shoulder dystocia, permanent and transient brachial plexus injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admissions. PMID- 22071066 TI - Fetal omphalocele ratios predict outcomes in prenatally diagnosed omphalocele. AB - OBJECTIVE: The objective of the study was to evaluate whether ratios considering omphalocele diameter relative to fetal biometric measurements perform better than giant omphalocele designation at predicting inability to achieve neonatal primary surgical closure. STUDY DESIGN: Cases of fetal omphalocele that underwent evaluation between May 2003 and July 2010 were identified. Inclusion was restricted to live births with plan for postnatal repair. Omphalocele diameter upon antenatal ultrasound was compared with abdominal circumference, femur length, and head circumference, yielding the respective omphalocele (O)/abdominal circumference (AC), O/femur length (FL), and O/head circumference (HC) ratios. The absolute measurements were used to classify giant lesions. Omphalocele ratios and giant omphalocele designations were evaluated as predictors of inability to achieve primary repair. RESULTS: Among 25 included cases, staged or delayed closure occurred in 52%. With an optimal cutoff of 0.21 or greater, O/HC best predicted the primary outcome (sensitivity, 84.6%; specificity, 58.3%; odds ratio, 7.7). The O/HC of 0.21 or greater outperformed giant designations. CONCLUSION: The O/HC of 0.21 or greater best predicted staged or delayed omphalocele closure. Giant omphalocele designation, regardless of definition, poorly predicted outcome. PMID- 22071067 TI - An initial miscarriage is associated with adverse pregnancy outcomes in the following pregnancy. AB - OBJECTIVE: The objective of the study was to determine whether 1 previous miscarriage is associated with an increased rate of adverse pregnancy outcomes in the following pregnancy. STUDY DESIGN: Second pregnancies of women with and without a miscarriage in their initial pregnancy were compared. Multivariable logistic regression models were constructed to control for confounders. RESULTS: Of 35,125 singleton deliveries in the second pregnancy, 5777 (16.4%) were of patients with an initial miscarriage. Multivariable analysis showed a significant association between a previous miscarriage and the following adverse pregnancy outcomes including premature rupture of membranes (odds ratio [OR], 2.22; 95% confidence interval [CI], 2.01-2.44), preterm delivery (OR, 1.34; 95% CI, 1.21 1.48), intrauterine growth restriction (OR, 1.24; 95% CI, 1.04-1.47), hypertensive disorders (OR 1.41; 95% CI 1.07-1.85), preeclampsia (OR, 1.63; 95% CI, 1.22-2.18), and cesarean delivery (OR, 1.59; 95% CI, 1.46-1.73). Perinatal mortality was significantly higher among women with an initial miscarriage (1.6% vs 1.0%; P < .001). CONCLUSION: An initial miscarriage is independently associated with adverse pregnancy outcomes. PMID- 22071068 TI - Assessment of the concordance among 2-tier, 3-tier, and 5-tier fetal heart rate classification systems. AB - OBJECTIVE: In 2008, a National Institute of Child Health and Human Development/Society for Maternal-Fetal Medicine-sponsored workshop on electronic fetal monitoring recommended a new fetal heart tracing interpretation system. Comparison of this 3-tier system with other systems is lacking. Our purpose was to determine the relationships between fetal heart rate categories for the 3 existing systems. METHODS: Three Maternal-Fetal Medicine specialists reviewed 120 fetal heart rates. All tracings were from term, singleton pregnancies with known umbilical artery pH. The fetal heart rates were classified by a 2-tier, 3-tier, and 5-tier system. RESULTS: Each Maternal-Fetal Medicine examiner reviewed 120 fetal heart rate segments. When compared with the 2-tier system, 0%, 54%, and 100% tracings in categories 1, 2, and 3 were "nonreassuring." There was strong concordance between category 1 and "green" as well as category 3 and "red" tracings. CONCLUSION: The 3-tier and 5-tier systems were similar in fetal heart rate interpretations for tracings that were either very normal or very abnormal. Whether one system is superior to the others in predicting fetal acidemia remains unknown. PMID- 22071069 TI - A faster nonsurgical solution very large fibroid tumors yielded to a new ablation strategy. PMID- 22071070 TI - Discussion: 'bariatric surgery and obstetric outcomes' by Josefsson et al. PMID- 22071072 TI - Maternal treatment with opioid analgesics and risk for birth defects. PMID- 22071073 TI - Opioid exposure and birth defects. PMID- 22071074 TI - Validation of HbA1c of 6.5% for diagnosing diabetes mellitus via the use of taxometric analysis. AB - PURPOSE: Previous studies in which authors examined the internal and external validity of a glycemic cut-point for diagnosis of diabetes mellitus have provided mixed results. The purpose of the current study was to test the internal validity of the HbA1c 6.5% cut-point with taxometric analysis. METHODS: Data on 14,798 participants were obtained from the National Health and Nutrition Examination Survey, years 1999-2008. Fasting plasma glucose and HbA1c were submitted to the taxometric procedures MAMBAC (mean above minus below a cut) and MAXSLOPE (MAXimum SLOPE). The comparison curve fit index was the outcome measure, with values less than 0.40 and greater than 0.60 indicative of dimensional and categorical solutions, respectively. RESULTS: In the full sample, MAXSLOPE and MAMBAC procedures yielded CCFIs of 0.778 and 0.872, respectively. Analyses were repeated in subgroups by age, sex, fasting insulin level, ethnicity, and year; the lowest comparison curve fit index measurement from any analysis was 0.706. CONCLUSIONS: These results support a categorical overdimensional model of diabetes, consistent with the new HbA1c cut-point recommendation. PMID- 22071075 TI - The effect of Cu2+ on interaction between flavonoids with different C-ring substituents and bovine serum albumin: structure-affinity relationship aspect. AB - Four flavonoids quercetin (QU), luteolin (LU), taxifolin (TA) and (+)-catechin (CA) with the same A- and B-rings but different C-ring substituents have been investigated for their binding to bovine serum albumin (BSA) in the absence and presence of Cu(2+) by means of various spectroscopic methods such as fluorescence, UV-visible and circular dichroism (CD). The results indicated that hydroxyl group at 3-position increased the binding affinities between flavonoids and BSA. The values of the binding affinities were in the order: QU>CA>TA>LU. The presence of Cu(2+) affected the interactions of flavonoids with BSA significantly. The binding affinities of QU and TA for BSA were decreased about 6.7% and 13.2%. However, the binding affinities of LU and CA for BSA were increased about 43.0% and 20.7%. The formation of Cu(2+)-flavonoid complex and steric hindrance together influenced the binding affinities of QU, LU and TA for BSA, while the conformational change of BSA may be the main reason for the increased binding affinity of CA for BSA. However, the quenching mechanism for QU, LU, TA and CA to BSA was based on static quenching combined with non radiative energy transfer irrespective of the absence or presence of Cu(2+). The UV-visible results showed the change in BSA conformation and the formation of flavonoid-Cu(2+) complex. The CD results also explained the conformational changes of BSA on binding with flavonoids. PMID- 22071076 TI - Influence of the geometry around the manganese ion on the peroxidase and catalase activities of Mn(III)-Schiff base complexes. AB - The peroxidase and catalase activities of eighteen manganese-Schiff base complexes have been studied. A correlation between the structure of the complexes and their catalytic activity is discussed on the basis of the variety of systems studied. Complexes 1-18 have the general formulae [MnL(n)(D)(2)](X)(H(2)O/CH(3)OH)(m), where L(n)=L(1)-L(13); D=H(2)O, CH(3)OH or Cl; m=0-2.5 and X=NO(3)(-), Cl(-), ClO(4)(-), CH(3)COO(-), C(2)H(5)COO(-) or C(5)H(11)COO(-). The dianionic tetradentate Schiff base ligands H(2)L(n) are the result of the condensation of different substituted (OMe-, OEt-, Br-, Cl-) hydroxybenzaldehyde with diverse diamines (1,2-diaminoethane for H(2)L(1) H(2)L(2); 1,2-diamino-2-methylethane for H(2)L(3)-H(2)L(4); 1,2-diamino-2,2 dimethylethane for H(2)L(5); 1,2-diphenylenediamine for H(2)L(6)-H(2)L(7); 1,3 diaminopropane for H(2)L(8)-H(2)L(11); 1,3-diamino-2,2-dimethylpropane for H(2)L(12)-H(2)L(13)). The new Mn(III) complexes [MnL(1)(H(2)O)Cl](H(2)O)(2.5) (2), [MnL(2)(H(2)O)(2)](NO(3))(H(2)O) (4), [MnL(6)(H(2)O)(2)][MnL(6)(CH(3)OH)(H(2)O)](NO(3))(2)(CH(3)OH) (8), [MnL(6)(H(2)O)(OAc)](H(2)O) (9) and [MnL(7)(H(2)O)(2)](NO(3))(CH(3)OH)(2) (12) were isolated and characterised by elemental analysis, magnetic susceptibility and conductivity measurements, redox studies, ESI spectrometry and UV, IR, paramagnetic (1)H NMR, and EPR spectroscopies. X-ray crystallographic studies of these complexes and of the ligand H(2)L(6) are also reported. The crystal structures of the rest of the complexes have been previously published and herein we have only revised their study by those techniques still not reported (EPR and (1)H NMR for some of these compounds) and which help to establish their structures in solution. Complexes 1-12 behave as more efficient mimics of peroxidase or catalase in contrast with 13-18. The analysis between the catalytic activity and the structure of the compounds emphasises the significance of the existence of a vacant or a labile position in the coordination sphere of the catalyst. PMID- 22071077 TI - The in vitro glycation of human serum albumin in the presence of Zn(II). AB - Amino groups of human serum albumin (HSA) can react non-enzymatically with carbonyl groups of reducing sugars to form advanced glycation end products (AGEs). These AGEs contribute to many of the chronic complications of diabetes including atherosclerosis, cataract formation and renal failure. The current study focused on in vitro non-enzymatic reactivity of glyceraldehyde (GA) and methylglyoxal (MG) with HSA and evaluated the rate and extent of AGE formation in the presence of varied concentrations of Zn(II). At normal physiological conditions, GA and MG readily react with HSA. The presence of Zn(II) in HSA-GA or HSA-MG incubation mixtures reduced AGE formation. This finding was confirmed by UV and fluorescence spectrometry, HPLC techniques, and matrix assisted laser desorption ionization mass spectrometry (MALDI-TOF). HPLC studies revealed decreased adduct formation of the glycated protein in the presence of Zn(II). The inhibition of AGE formation was intense at elevated Zn(II) concentrations. The results of this study suggest that Zn(II) may prove to be a potent agent in reducing AGE formation. PMID- 22071078 TI - Kinetic studies of oxygen atom transfer reactions from trans-dioxoruthenium(VI) porphyrins to sulfides. AB - The kinetics of the reactions of three trans-dioxoruthenium(VI) porphyrin derivatives with organic sulfides were measured. The dioxo systems studied were 5,10,15,20-tetramesityl porphyrin-dioxoruthenium(VI) (2a), 5,10,15,20 tetraphenylporphyrin-dioxoruthenium(VI) (2b), and 5,10,15,20 tetrakis(pentafluorophenyl)porphyrin-dioxoruthenium(VI) (2c). Species 2 were competent oxidants and reacted rapidly with thioanisoles to generate the corresponding sulfoxides. Typical second-order rate constants determined from pseudo-first-order kinetic studies for sulfoxidation reactions are 8-60 M(-1)s( 1), which are 3 orders of magnitude larger in comparison with those of well studied alkene epoxidations and activated C-H bond oxidations by the same dioxo species. For a given sulfide substrate, the reactivity order for the dioxoruthenium(VI) species was 2a<2b<2c, which is in agreement with expectation on the basis of the electron-withdrawing and steric effects of the porphyrin macrocycles. Various para-substituted thioanisoles react in a narrow kinetic range with the same dioxo species. The kinetic results obtained in this study indicate a concerted oxygen atom transfer and/or electron transfer followed by oxygen transfer mechanism from oxidant to sulfide. Competition kinetic reactions with a catalytic amount of porphyrin ruthenium(II) species and a terminal oxidant give relative rate constants for sulfoxidations of competing substrates that are somewhat smaller than the ratios of absolute rate constants, implying a multiple oxidant model for sulfoxidation reactions. PMID- 22071079 TI - Synthesis and in vitro evaluation of palladium(II) salicylaldiminato thiosemicarbazone complexes against Trichomonas vaginalis. AB - Eight mononuclear Pd(II) complexes containing salicylaldiminato thiosemicarbazones (saltsc-R; where R=H (1), 3-OMe (2), 3-(t)Bu (3) and 5-Cl (4)) as dinegative tridentate ligands were prepared by the reaction of the corresponding thiosemicarbazone with the precursor Pd(L)(2)Cl(2) (L=phosphatriazaadamantane or 4-picoline) in the presence of a weak base. These complexes (9-16) were characterised by a range of spectroscopic and analytical techniques including NMR spectroscopy and X-ray diffraction. These complexes along with four other Pd(II) analogues (5-8) were screened for activity in vitro against the Trichomonas vaginalis parasite. Preliminary results show that the type of ancillary ligand as well as the substituents on the aromatic ring of the salicylaldiminato thiosemicarbazone ligand influences the antiparasitic activity of these complexes. PMID- 22071080 TI - Non-intercalative binding mode of bridged binuclear chiral Ru(II) complexes to native duplex DNA. AB - A pair of chiral binuclear ruthenium(II) complexes were prepared and their binding affinities towards double stranded native DNA were assessed by observing isotropic absorption, polarized light spectra - circular and linear dichroism (CD and LD), fluorescence quenching and DNA thermal denaturation. Upon binding to DNA, the complexes produced LD signals consisting of positive and negative signals in the absorption region, although they exhibited red shift and hypochromism in the absorption spectrum. These contrasting observations indicated that the binding modes of the complexes are largely deviated from classical intercalative binding. Groove binding of the complexes to DNA was found to be more likely than intercalative binding. The small increase of DNA melting temperature in the presence of the complexes indicated a predominance of DNA groove binding. The absence of "molecular light switch effect" further supported non-intercalative binding. The groove binding propensity of complexes was also supported by comparison of the resulting data with the [Ru(phen)(2)(dppz)](2+). PMID- 22071081 TI - Selected gold compounds cause pronounced inhibition of Falcipain 2 and effectively block P. falciparum growth in vitro. AB - A number of structurally diverse gold compounds were evaluated as possible inhibitors of Falcipain 2 (Fp2), a cysteine protease from P. falciparum that is a validated target for the development of novel antimalarial drugs. Remarkably, most tested compounds caused pronounced but reversible inhibition of Fp2 with K(i) values falling in the micromolar range. Enzyme inhibition is basically ascribed to gold binding to catalytic active site cysteine. The same gold compounds were then tested for their ability to inhibit P. falciparum growth in vitro; important parasite growth inhibition was indeed observed. However, careful analysis of the two sets of data failed to establish any direct correlation between enzyme inhibition and reduction of P. falciparum growth suggesting that Fp2 inhibition represents just one of the various mechanisms through which gold compounds effectively antagonize P. falciparum replication. PMID- 22071082 TI - Effects of terbium chelate structure on dipicolinate ligation and the detection of Bacillus spores. AB - Terbium-sensitized luminescence and its applicability towards the detection of Bacillus spores such as anthrax are of significant interest to research in biodefense and medical diagnostics. Accordingly, we have measured the effects of terbium chelation upon the parameters associated with dipicolinate ligation and spore detection. Namely, the dissociation constants, intrinsic brightness, luminescent lifetimes, and biological stabilities for several Tb(chelate)(dipicolinate)(x) complexes were determined using linear, cyclic, and aromatic chelators of differing structure and coordination number. This included the chelator array of NTA, BisTris, EGTA, EDTA, BAPTA, DO2A, DTPA, DO3A, and DOTA (respectively, 2,2',2"-nitrilotriacetic acid; 2,2-bis(hydroxymethyl)-2,2',2" nitrilotriethanol; ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid; ethylenediamine-N,N,N',N'-tetraacetic acid; 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid; 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid; diethylenetriamine-N,N,N',N",N"-pentaacetic acid; 1,4,7,10-tetraazacyclododecane 1,4,7-triacetic acid; and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Our study has revealed that the thermodynamic and temporal emission stabilities of the Tb(chelate)(dipicolinate)(x) complexes are directly related to chelate rigidity and a ligand stoichiometry of x=1, and that chelators possessing either aromaticity or low coordination numbers are destabilizing to the complexes when in extracts of an extremotolerant Bacillus spore. Together, our results demonstrate that both Tb(EDTA) and Tb(DO2A) are chemically and biochemically stable and thus applicable as respectively low and high-cost luminescent reporters for spore detection, and thereby of significance to institutions with developing biodefense programs. PMID- 22071083 TI - Synthesis and evaluation of the europium(III) and zinc(II) complexes as luminescent bioprobes in high content cell-imaging analysis. AB - Novel phenanthroline derivatives and their europium(III) and zinc(II) complexes have been prepared in up to 92%. In contrast to the stable zinc complexes, the europium compounds exhibit a strong luminescence in THF solution. However, quenching of the emission is observed in DMSO indicating complete dissociation of the complexes back to free ligands in this solvent. (1)H NMR studies of the Eu(III)-complexes 5 and 6 also confirmed the existence of different states depending on the solvent used. Moreover, it was found that compound 5 is stable in EtOH-PBS solutions; here a strong signal in the emission spectra corresponding to the europium ion was detected. No spectral changes were observed for the zinc(II) complexes, they were shown to be stable in the media. These metal complexes can be used as fluorescence markers for the diagnosis of oesophageal squamous carcinoma (OE21) cells at low concentrations. Cell images were acquired using the compounds 5, 7-9 as luminescent agents. The first images were taken already after 20 min incubation time at a very low concentration range (0.7-1.6 MUM). PMID- 22071084 TI - Low-lying electronic states of the ferrous high-spin (S=2) heme in deoxy-Mb and deoxy-Hb studied by highly-sensitive multi-frequency EPR. AB - The low-lying electronic states of the ferrous high-spin heme in deoxy-myoglobin (deoxy-Mb) and deoxy-hemoglobin (deoxy-Hb) were probed by multi-frequency electron paramagnetic resonance (MFEPR) spectroscopy. An unexpected broad EPR signal was measured at the zero magnetic field using cavity resonators at 34-122 GHz that could not be simulated using any parameter sets for the S=2 spin Hamiltonian assuming spin quintet states in the (5)B(2) ground state. Furthermore, we have observed novel, broad EPR signals measured at 70-220 GHz and 1.5K using a single pass transmission probe. These signals are attributed to the ferrous high-spin heme in deoxy-Mb and deoxy-Hb. The resonant peaks shifted to a higher magnetic field with increasing frequency. The energy level separation between the ground singlet and the first excited state at the zero magnetic field was directly estimated to be 3.5 cm(-1) for deoxy-Hb. For deoxy-Mb, the first two excited singlet states are separated by 3.3 cm(-1) and 6.5 cm(-1), respectively, from the ground state. The energy gap at the zero magnetic field is directly derived from our MFEPR for deoxy-Mb and deoxy-Hb and strongly supports the theoretical analyses based on the Mossbauer and magnetic circular dichroism experiments. PMID- 22071085 TI - Synthesis, structure, DNA binding and cleavage properties of ternary amino acid Schiff base-phen/bipy Cu(II) complexes. AB - Ternary Cu(II) complexes [Cu(II)(saltrp)(B)] (1,2), (saltrp=salicylidene tryptophan, B=1,10 phenathroline (1) or 2,2' bipyridine (2)) were synthesized and characterized. Complex 2 was structurally characterized by single crystal X-ray crystallography. The molecular structure shows a distorted square pyramidal coordination geometry (CuN(3)O(2)) in which the ONO donor Schiff base is bonded to the Cu(II) in the basal plane. The N,N donor heterocyclic base displays an axial-equatorial binding mode. CT-DNA binding studies revealed that the complexes show good binding propensity (Intrinsic binding constant, K(b)=3.32*10(5) M(-1) for 1 and K(b)=3.10*10(5) M(-1) for 2). The catalytic role of these complexes in the oxidative and hydrolytic cleavage of DNA was studied in detail. Complex 1 binds and cleaves DNA more efficiently as compared to 2. From the kinetic experiments, rate constants for the hydrolysis of phosphodiester bond of DNA backbone were determined as 1.94 h(-1) and 1.05 h(-1) for 1 and 2 respectively. It amounts to (2.93-5.41)*10(7) fold rate enhancement compared to uncatalyzed double stranded DNA, which is impressive as compared to related Cu(II) Schiff base complexes. PMID- 22071086 TI - 3,5-diacetyl-1,2,4-triazol bis(4N-substituted thiosemicarbazone) palladium(II) complexes: synthesis, structure, antiproliferative activity and low toxicity on normal kidney cells. AB - Treatment of (4)N-monosubstituted bis(thiosemicarbazone) ligands of 3,5-diacetyl 1,2,4-triazol series with lithium tetrachloridopalladate gave the dinuclear complexes of general formula [Pd(MU-H(3)L(1-5))](2), but using dichloridobistriphenylphosphinepalladium(II) salt, the first mononuclear bis(thiosemicarbazone)-palladium-triphenylphosphine complexes of the 3,5-diacetyl 1,2,4-triazol series, [Pd(H(3)L(1-5))PPh(3)], have been obtained. All the compounds have been characterized by elemental analysis and by IR and NMR spectroscopy, and the crystal and molecular structures of dinuclear complexes [Pd(MU-H(3)L(3))](2) and [Pd(MU-H(3)L(5))](2) as well as mononuclear complexes [Pd(H(3)L(1))PPh(3)], [Pd(H(3)L(2))PPh(3)], [Pd(H(3)L(3))PPh(3)] and [Pd(H(3)L(4))PPh(3)] have been determined by X-ray crystallography. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. Subsequent toxicity study, on normal renal LLC-PK1 cells, shows that all compounds investigated exhibit very low toxicity on kidney cells with respect to cisplatin. PMID- 22071087 TI - Synthesis and biological studies of 4', 7, 8-trihydroxy-isoflavone metal complexes. AB - A new series of complexes of a ligand 4', 7, 8-trihydroxy-isoflavone with transition metal (zinc, copper, manganese, nickel, cobalt) and selenium have been synthesized and characterized with the aid of elemental analysis, IR, electron ionization mass spectrum (EI-MS) and (1)H NMR spectrometric techniques. The compounds were evaluated for their in vitro antibacterial activities and antitumor properties. The metal complexes were found to be more active than the free ligand. Investigation on the interaction between the complexes and calf thymus DNA (CT DNA) showed that the absorbance of CT DNA increased and the maximum peak (lambda(max)=260 nm) red-shifted, while the intensity of fluorescence spectra of Epstein-Bart DNA (EB-DNA) gradually weakened, which indicated that all of these metal complexes tightly combined with CT DNA. PMID- 22071088 TI - Lipophilic Pt(II) complexes with selective efficacy against cisplatin-resistant testicular cancer cells. AB - A series of dichloridoplatinum(II) complexes with selective and high cytotoxicity [IC(90)(96h)<=3 MUM] against cisplatin-resistant 1411HP testicular cancer cells were identified. They bear stationary 6-aminomethylnicotinate or 2,4 diaminobutyrate ligands esterified with lipophilic terpenyl residues, i.e., ( )/(+)-menthyl, (+)-cedrenyl, (-)-menthoxypropyl, or with a decyl-tethered 1,1,2 triphenylethene. They accumulated to a larger extent in 1411HP cells than in cells of the cisplatin-sensitive H12.1 germ cell tumour. Their mechanism of apoptosis induction differed from that of cisplatin by being independent of p53 and of caspase-3 activation and by an early loss of the mitochondrial membrane potential. The new complexes are promising candidates for the treatment of cisplatin-resistant testicular tumours. PMID- 22071089 TI - Replacement of the axial copper ligand methionine with lysine in amicyanin converts it to a zinc-binding protein that no longer binds copper. AB - The mutation of the axial ligand of the type I copper protein amicyanin from Met to Lys results in a protein that is spectroscopically invisible and redox inactive. M98K amicyanin acts as a competitive inhibitor in the reaction of native amicyanin with methylamine dehydrogenase indicating that the M98K mutation has not affected the affinity for its natural electron donor. The crystal structure of M98K amicyanin reveals that its overall structure is very similar to native amicyanin but that the type I binding site is occupied by zinc. Anomalous difference Fourier maps calculated using the data collected around the absorption edges of copper and zinc confirm the presence of Zn(2+) at the type I site. The Lys98 NZ donates a hydrogen bond to a well-ordered water molecule at the type I site which enhances the ability of Lys98 to provide a ligand for Zn(2+). Attempts to reconstitute M98K apoamicyanin with copper resulted in precipitation of the protein. The fact that the M98K mutation generated such a selective zinc-binding protein was surprising as ligation of zinc by Lys is rare and this ligand set is unique for zinc. PMID- 22071090 TI - Non-steroidal anti-inflammatory drug diflunisal interacting with Cu(II). Structure and biological features. AB - Copper(II) complexes with the non-steroidal anti-inflammatory drug diflunisal in the presence of N,N-dimethylformamide or nitrogen donor heterocyclic ligands (pyridine, 1,10-phenanthroline, 2,2'-bipyridine or 2,2'-bipyridylamine) have been synthesized and characterized. The deprotonated diflunisal ligands are coordinated to Cu(II) ion through carboxylato oxygen atoms. The crystal structures of [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] 1 and [bis(diflunisal)bis(pyridine)copper(II)], 2 have been determined by X-ray crystallography and are the first reported crystal structures of diflunisal complexes. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) suggests binding of the complexes to CT DNA with the dinuclear [tetrakis(diflunisal)bis(N,N-dimethylformamide)dicopper(II)] compound exhibiting the highest binding constant, K(b). Intercalative binding mode may also be concluded using cyclic voltammetry and solution viscosity measurements of the complexes in the presence of CT DNA. Competitive studies with ethidium bromide (EB) indicate that the complexes can displace the DNA-bound EB suggesting competition with EB. Diflunisal and its complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values. PMID- 22071091 TI - A novel approach for the selective determination of tryptophan in blood serum in the presence of tyrosine based on the electrochemical reduction of oxidation product of tryptophan formed in situ on graphite electrode. AB - In this study, a novel method was proposed for the selective determination of tryptophan (TRP) in blood serum in the presence of tyrosine. This method is based on the electrochemical reduction of 2-amino-3-(5-oxo-3,5-dihydro-2H-indol-3-yl) propionic acid (5-O-3,5DH-TRP) formed by the oxidation of TRP on the electrochemically treated pencil graphite (ETPG) electrode surface at a suitable potential value. The parameters affecting the TRP determination were deeply investigated. The optimal pH value was determined as 3. The highest reduction current intensity was obtained at the accumulation potential and time values of +0.95 V and 120 s, respectively. The reduction peak current values of 5-O-3,5DH TRP versus TRP concentration at the ETPG electrode showed linearity in the range from 0.5 MUM to 50.0 MUM (R(2)=0.9962) with a detection limit of 0.05 MUM (S/N=3). The reduction peak intensity of 5-O-3,5DH-TRP on the ETPG electrode showed no significant change in the presence of different interfering substances. The analytical application of the proposed novel method was successfully tested by using human blood serum samples. PMID- 22071092 TI - The role of microRNAs in neural stem cell-supported endothelial morphogenesis. AB - Functional signaling between neural stem/progenitor cells (NSPCs) and brain endothelial cells (ECs) is essential to the coordination of organized responses during initial embryonic development and also during tissue repair, which occurs following brain injury. In this study, we investigated the molecular mechanisms underlying this functional signaling, using primary mouse brain ECs and NSPCs from embryonic mouse brain. EC/NSPC co-culture experiments have revealed that neural progenitors secrete factors supporting angiogenesis, which induce noticeable changes in endothelial morphology. We demonstrate that NSPCs influence the expression of mTOR and TGF-beta signaling pathway components implicated in the regulation of angiogenesis. Endothelial morphogenesis, an essential component of vascular development, is a complex process involving gene activation and the upregulation of specific cell signaling pathways. Recently identified small molecules, called microRNAs (miRNAs), regulate the expression of genes and proteins in many tissues, including brain and vasculature. We found that NSPCs induced considerable changes in the expression of at least 24 miRNAs and 13 genes in ECs. Three NSPC-regulated EC miRNAs were identified as the potential primary mediators of this NSPC/EC interaction. We found that the specific inhibition, or overexpression, of miRNAs miR-155, miR-100, and miR-let-7i subsequently altered the expression of major components of the mTOR, TGF-beta and IGF-1R signaling pathways in ECs. Overexpression of these miRNAs in ECs suppressed, while inhibition activated, the in vitro formation of capillary-like structures, a process representative of EC morphogenesis. In addition, we demonstrate that inhibition of FGF, VEGF, and TGF-beta receptor signaling abolished NSPC-promoted changes in the endothelial miRNA profiles. Our findings demonstrate that NSPCs induce changes in the miRNA expression of ECs, which are capable of activating angiogenesis by modulating distinct cell signaling pathways. PMID- 22071093 TI - Occurrence, characteristics, and impact of chronic pain in formerly abused women. AB - The purposes of this study were to describe the occurrence of chronic pain and to evaluate for differences in pain characteristics and intimate partner violence between women who reported mild compared with moderate to severe chronic pain. A convenience sample of community-based women (N = 84) was recruited. The 77% of women who reported chronic pain were dichotomized into two groups. Women with moderate to severe pain (n = 49) were significantly more likely to be unemployed, to be in the abusive relationship longer, to report more minor injuries and threats of violence, and to report pain in multiple locations that significantly interfered with every aspect of their lives. PMID- 22071094 TI - From the voices of women: facilitating survivor access to IPV services. AB - This mixed-method study investigated perceptions women domestic violence survivors/victims have about why women do not seek help from formal support structures and actions domestic helping agencies can take to facilitate survivor access to services. Congruent with previous research, quantitative analysis identified 17 reasons women do not seek help from formal support structures. Expanding current knowledge, concept mapping revealed six ways family violence programs can better reach women in abusive relationships, including (1) remove barriers to services, (2) improve comfort with services, (3) "talk about it," (4) improve community awareness, (5) victim-targeted marketing, and (6) "I honestly don't know." PMID- 22071095 TI - Legislating gender inequalities: the nature and patterns of domestic violence experienced by South Asian women with insecure immigration status in the United Kingdom. AB - Research on domestic violence documents the particular vulnerability of immigrant women due to reasons including social isolation, language barriers, lack of awareness about services, and racism on the part of services. Based on qualitative interviews with 30 South Asian women with insecure immigration status residing in Yorkshire and Northwest England, this article explores how inequalities created by culture, gender, class, and race intersect with state immigration and welfare policies in the United Kingdom, thereby exacerbating structures of patriarchy within minority communities. It is within these contexts that South Asian women with insecure immigration status experience intensified forms and specific patterns of abuse. PMID- 22071096 TI - Tanzanian lessons in using non-physician clinicians to scale up comprehensive emergency obstetric care in remote and rural areas. AB - BACKGROUND: With 15-30% met need for comprehensive emergency obstetrical care (CEmOC) and a 3% caesarean section rate, Tanzania needs to expand the number of facilities providing these services in more remote areas. Considering severe shortage of human resources for health in the country, currently operating at 32% of the required skilled workforce, an intensive three-month course was developed to train non-physician clinicians for remote health centres. METHODS: Competency based curricula for assistant medical officers' (AMOs) training in CEmOC, and for nurses, midwives and clinical officers in anaesthesia and operation theatre etiquette were developed and implemented in Ifakara, Tanzania. The required key competencies were identified, taught and objectively assessed. The training involved hands-on sessions, lectures and discussions. Participants were purposely selected in teams from remote health centres where CEmOC services were planned. Monthly supportive supervision after graduation was carried out in the upgraded health centres RESULTS: A total of 43 care providers from 12 health centres located in 11 rural districts in Tanzania and 2 from Somalia were trained from June 2009 to April 2010. Of these 14 were AMOs trained in CEmOC and 31 nurse midwives and clinical officers trained in anaesthesia. During training, participants performed 278 major obstetric surgeries, 141 manual removal of placenta and evacuation of incomplete and septic abortions, and 1161 anaesthetic procedures under supervision. The first 8 months after introduction of CEmOC services in 3 health centres resulted in 179 caesarean sections, a remarkable increase of institutional deliveries by up to 300%, decreased fresh stillbirth rate (OR: 0.4; 95% CI: 0.1-1.7) and reduced obstetric referrals (OR: 0.2; 95% CI: 0.1-0.4)). There were two maternal deaths, both arriving in a moribund condition. CONCLUSIONS: Tanzanian AMOs, clinical officers, and nurse-midwives can be trained as a team, in a three-month course, to provide effective CEmOC and anaesthesia in remote health centres. PMID- 22071097 TI - Intracellular pathways and nuclear localization signal peptide-mediated gene transfection by cationic polymeric nanovectors. AB - Polyethylenimine (PEI) - based polymers are promising cationic nanovectors. A good understanding of the mechanism by which cationic polymers/DNA complexes are internalized and delivered to nuclei helps to identify which transport steps may be manipulated in order to improve the transfection efficiency. In this work, cell internalization and trafficking of PEI-CyD (PC) composed of beta cyclodextrin (beta-CyD) and polyethylenimine (PEI, Mw 600) are studied. The results show that the PC transfected DNA is internalized by binding membrane associated proteoglycans. The endocytic pathway of the PC particles is caveolae- and clathrin-dependent with both pathways converging to the lysosome. The intracellular fate of the PC provides visual evidence that it can escape from the lysosome. Lysosomal inhibition with chloroquine has no effect on PC mediated transfection implying that blocking the lysosomal traffic does not improve transfection. To improve the nuclear delivery of PC transfected DNA, nuclear localization signal (NLS) peptides are chosen to conjugate and combine with the PC. Compared to PC/pDNA, PC-NLS/pDNA, and PC/pDNA/NLS can effectively improve gene transfection in dividing and non-dividing cells. PMID- 22071098 TI - The CD44/integrins interplay and the significance of receptor binding and re presentation in the uptake of RGD-functionalized hyaluronic acid. AB - We have studied the interplay between two endocytic receptors for a carrier structure bearing two complementary ligands. Hyaluronic acid (HA; three different molecular weights) was functionalized with an RGD-containing peptide; this ancillary ligand allows the macromolecule to bind to alpha(v) integrins in addition to the classical HA internalization receptor (CD44). The uptake of HA RGD and of native HA was assessed in a phagocytic cell model (J774.2 murine macrophages), studying the kinetics of internalization and its mechanistic details. Indications of a synergic binding to integrins and CD44 emerged for HA RGD; possibly, a first binding to integrins allows for a pre-concentration of the macromolecule on the cell surface, which is then followed by its binding to CD44. The endocytic mechanism and kinetics appeared then dominated by CD44, which has a much slower turnover than integrins. In this study we have demonstrated that the knowledge of the rate-determining steps of the internalization of a carrier is necessary for assessing its performance. In this case, the presence of multiple ligands on a carrier was beneficial in some respect (e.g. in improved binding/targeting), but may not be sufficient to overcome penetration barriers that arise from slow receptor re-presentation. PMID- 22071099 TI - Modulation of the migration and differentiation potential of adult bone marrow stromal stem cells by nitric oxide. AB - Nitric oxide (NO) is a diffusible free radical, which serves as a pluripotent intracellular messenger in numerous cell systems. NO has been demonstrated to regulate actin dependent cellular functions and functions as a putative inductive agent in directing stem cells differentiation. In this study, we investigated the effect of exogenous NO on the kinetics of movement and morphological changes in adult bone marrow stromal cells (BMSCs) in a wound healing model of cellular migration. Cellular migration and morphological changes were determined by measurement of changes in the area and fractal dimension of BMSCs monolayer as a function of time in the presence of an NO donor (S-Nitroso-N-Acetyl-D,L Penicillamine, SNAP) compared to untreated BMSCs. Response of the BMSCs' actin cytoskeleton and desmin to NO was assessed by determining changes in their integrated optical density (IOD) and fractal dimension at 24 h and 7 days. NO suppressed BMSCs' migration accompanied by a reduction in cell size, with maintenance of their stellate to polygonal morphology. In response to NO, the actin cytoskeleton expressed an increase in randomness but maintained a constant amount of F-actin relative to the cell size. The presence of NO also induced an increase in randomly organized cytoplasmic desmin. These data suggest that NO has an apparent inductive effect on adult BMSCs and is capable of initiating phenotypic change at the gross cellular, cytoskeletal and molecular levels. It is apparent, however, that additional factors or conditions are required to further drive the differentiation of adult BMSCs into specific phenotypes, such as cardiomyocytes. PMID- 22071100 TI - Three-dimensional cancer-bone metastasis model using ex-vivo co-cultures of live calvarial bones and cancer cells. AB - One of the major limitations of studying cancer-bone metastasis has been the lack of an appropriate ex-vivo model which can be used under defined conditions that simulates closely the in vivo live bone microenvironment in response to cancer bone interactions. We have developed and utilized a three-dimensional (3D) cancer bone metastasis model using free-floating live mouse calvarial bone organs in the presence of cancer cells in a roller tube system. In such co-cultures under hypoxia and a specifically defined bone remodeling stage, viz., resorption system, cancer cells showed a remarkable affinity and specificity for the "endosteal side" of the bone where they colonize and proliferate. This was concurrent with differentiation of resident stem/progenitor cells to osteoclasts and bone resorption. In contrast, under bone formation conditions this model revealed different pathophysiology where the breast cancer cells continued to induce osteoclastic bone resorption whereas prostate cancer cells led to osteoblastic bone formation. The current 3D model was used to demonstrate its application to studies involving chemical and biochemical perturbations in the absence and presence of cancer cells and cellular responses. We describe proof-of principle with examples of the broad versatility and multi-faceted application of this model that adds another dimension to the ongoing studies in the cancer-bone metastasis arena. PMID- 22071101 TI - Seven up acts as a temporal factor during two different stages of neuroblast 5-6 development. AB - Drosophila embryonic neuroblasts generate different cell types at different time points. This is controlled by a temporal cascade of Hb->Kr->Pdm->Cas->Grh, which acts to dictate distinct competence windows sequentially. In addition, Seven up (Svp), a member of the nuclear hormone receptor family, acts early in the temporal cascade, to ensure the transition from Hb to Kr, and has been referred to as a 'switching factor'. However, Svp is also expressed in a second wave within the developing CNS, but here, the possible role of Svp has not been previously addressed. In a genetic screen for mutants affecting the last-born cell in the embryonic NB5-6T lineage, the Ap4/FMRFamide neuron, we have isolated a novel allele of svp. Expression analysis shows that Svp is expressed in two distinct pulses in NB5-6T, and mutant analysis reveals that svp plays two distinct roles. In the first pulse, svp acts to ensure proper downregulation of Hb. In the second pulse, which occurs in a Cas/Grh double-positive window, svp acts to ensure proper sub-division of this window. These studies show that a temporal factor may play dual roles, acting at two different stages during the development of one neural lineage. PMID- 22071102 TI - The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification. AB - The generation of astrocytes during the development of the mammalian spinal cord is poorly understood. Here, we demonstrate for the first time that the extracellular matrix glycoprotein tenascin C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that tenascin C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of tenascin C leads to a sustained generation and delayed migration of Fgfr3-expressing immature astrocytes in vivo. Consistent with an increased generation of astroglial cells, we documented an increased number of GFAP-positive astrocytes at later stages. Mechanistically, we could demonstrate an upregulation and domain shift of the patterning genes Nkx6.1 and Nkx2.2 in vivo. In addition, sulfatase 1, a known downstream target of Nkx2.2 in the ventral spinal cord, was also upregulated. Sulfatase 1 regulates growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this function, we observed changes in both FGF2 and EGF responsiveness of spinal cord neural precursor cells. Taken together, our data implicate Tnc in the regulation of proliferation and lineage progression of astroglial progenitors in specific domains of the developing spinal cord. PMID- 22071103 TI - Pitx1 is necessary for normal initiation of hindlimb outgrowth through regulation of Tbx4 expression and shapes hindlimb morphologies via targeted growth control. AB - The forelimbs and hindlimbs of vertebrates are morphologically distinct. Pitx1, expressed in the hindlimb bud mesenchyme, is required for the formation of hindlimb characteristics and produces hindlimb-like morphologies when misexpressed in forelimbs. Pitx1 is also necessary for normal expression of Tbx4, a transcription factor required for normal hindlimb development. Despite the importance of this protein in these processes, little is known about its mechanism of action. Using a transgenic gene replacement strategy in a Pitx1 mutant mouse, we have uncoupled two discrete functions of Pitx1. We show that, firstly, this protein influences hindlimb outgrowth by regulating Tbx4 expression levels and that, subsequently, it shapes hindlimb bone and soft tissue morphology independently of Tbx4. We provide the first description of how Pitx1 sculpts the forming hindlimb skeleton by localised modulation of the growth rate of discrete elements. PMID- 22071104 TI - Eph/ephrin interactions modulate muscle satellite cell motility and patterning. AB - During development and regeneration, directed migration of cells, including neural crest cells, endothelial cells, axonal growth cones and many types of adult stem cells, to specific areas distant from their origin is necessary for their function. We have recently shown that adult skeletal muscle stem cells (satellite cells), once activated by isolation or injury, are a highly motile population with the potential to respond to multiple guidance cues, based on their expression of classical guidance receptors. We show here that, in vivo, differentiated and regenerating myofibers dynamically express a subset of ephrin guidance ligands, as well as Eph receptors. This expression has previously only been examined in the context of muscle-nerve interactions; however, we propose that it might also play a role in satellite cell-mediated muscle repair. Therefore, we investigated whether Eph-ephrin signaling would produce changes in satellite cell directional motility. Using a classical ephrin 'stripe' assay, we found that satellite cells respond to a subset of ephrins with repulsive behavior in vitro; patterning of differentiating myotubes is also parallel to ephrin stripes. This behavior can be replicated in a heterologous in vivo system, the hindbrain of the developing quail, in which neural crest cells are directed in streams to the branchial arches and to the forelimb of the developing quail, where presumptive limb myoblasts emigrate from the somite. We hypothesize that guidance signaling might impact multiple steps in muscle regeneration, including escape from the niche, directed migration to sites of injury, cell-cell interactions among satellite cell progeny, and differentiation and patterning of regenerated muscle. PMID- 22071106 TI - Novel functions of Noggin proteins: inhibition of Activin/Nodal and Wnt signaling. AB - The secreted protein Noggin1 is an embryonic inducer that can sequester TGFbeta cytokines of the BMP family with extremely high affinity. Owing to this function, ectopic Noggin1 can induce formation of the headless secondary body axis in Xenopus embryos. Here, we show that Noggin1 and its homolog Noggin2 can also bind, albeit less effectively, to ActivinB, Nodal/Xnrs and XWnt8, inactivation of which, together with BMP, is essential for the head induction. In support of this, we show that both Noggin proteins, if ectopically produced in sufficient concentrations in Xenopus embryo, can induce a secondary head, including the forebrain. During normal development, however, Noggin1 mRNA is translated in the presumptive forebrain with low efficiency, which provides the sufficient protein concentration for only its BMP-antagonizing function. By contrast, Noggin2, which is produced in cells of the anterior margin of the neural plate at a higher concentration, also protects the developing forebrain from inhibition by ActivinB and XWnt8 signaling. Thus, besides revealing of novel functions of Noggin proteins, our findings demonstrate that specification of the forebrain requires isolation of its cells from BMP, Activin/Nodal and Wnt signaling not only during gastrulation but also at post-gastrulation stages. PMID- 22071105 TI - The peripheral nervous system supports blood cell homing and survival in the Drosophila larva. AB - Interactions of hematopoietic cells with their microenvironment control blood cell colonization, homing and hematopoiesis. Here, we introduce larval hematopoiesis as the first Drosophila model for hematopoietic colonization and the role of the peripheral nervous system (PNS) as a microenvironment in hematopoiesis. The Drosophila larval hematopoietic system is founded by differentiated hemocytes of the embryo, which colonize segmentally repeated epidermal-muscular pockets and proliferate in these locations. Importantly, we show that these resident hemocytes tightly colocalize with peripheral neurons and we demonstrate that larval hemocytes depend on the PNS as an attractive and trophic microenvironment. atonal (ato) mutant or genetically ablated larvae, which are deficient for subsets of peripheral neurons, show a progressive apoptotic decline in hemocytes and an incomplete resident hemocyte pattern, whereas supernumerary peripheral neurons induced by ectopic expression of the proneural gene scute (sc) misdirect hemocytes to these ectopic locations. This PNS-hematopoietic connection in Drosophila parallels the emerging role of the PNS in hematopoiesis and immune functions in vertebrates, and provides the basis for the systematic genetic dissection of the PNS-hematopoietic axis in the future. PMID- 22071108 TI - Msx1 and Msx2 promote meiosis initiation. AB - The mechanisms regulating germ line sex determination and meiosis initiation are poorly understood. Here, we provide evidence for the involvement of homeobox Msx transcription factors in foetal meiosis initiation in mammalian germ cells. Upon meiosis initiation, Msx1 and Msx2 genes are strongly expressed in the foetal ovary, possibly stimulated by soluble factors found there: bone morphogenetic proteins Bmp2 and Bmp4, and retinoic acid. Analysis of Msx1/Msx2 double mutant embryos revealed a majority of undifferentiated germ cells remaining in the ovary and, importantly, a decrease in the number of meiotic cells. In vivo, the Msx1/Msx2 double-null mutation prevented full activation of Stra8, a gene required for meiosis. In F9 cells, Msx1 can bind to Stra8 regulatory sequences and Msx1 overexpression stimulates Stra8 transcription. Collectively, our data demonstrate for the first time that some homeobox genes are required for meiosis initiation in the female germ line. PMID- 22071107 TI - Rho GTPase controls Drosophila salivary gland lumen size through regulation of the actin cytoskeleton and Moesin. AB - Generation and maintenance of proper lumen size is important for tubular organ function. We report on a novel role for the Drosophila Rho1 GTPase in control of salivary gland lumen size through regulation of cell rearrangement, apical domain elongation and cell shape change. We show that Rho1 controls cell rearrangement and apical domain elongation by promoting actin polymerization and regulating F actin distribution at the apical and basolateral membranes through Rho kinase. Loss of Rho1 resulted in reduction of F-actin at the basolateral membrane and enrichment of apical F-actin, the latter accompanied by enrichment of apical phosphorylated Moesin. Reducing cofilin levels in Rho1 mutant salivary gland cells restored proper distribution of F-actin and phosphorylated Moesin and rescued the cell rearrangement and apical domain elongation defects of Rho1 mutant glands. In support of a role for Rho1-dependent actin polymerization in regulation of gland lumen size, loss of profilin phenocopied the Rho1 lumen size defects to a large extent. We also show that Ribbon, a BTB domain-containing transcription factor functions with Rho1 in limiting apical phosphorylated Moesin for apical domain elongation. Our studies reveal a novel mechanism for controlling salivary gland lumen size, namely through Rho1-dependent actin polymerization and distribution and downregulation of apical phosphorylated Moesin. PMID- 22071109 TI - Molecular basis for Flk1 expression in hemato-cardiovascular progenitors in the mouse. AB - The mouse Flk1 gene is expressed in various mesodermal progenitor cells of developing embryos. Recent studies have shown that Flk1 expression marks multipotent mesodermal progenitors, giving rise to various hemato-cardiovascular cell lineages during development. Flk1 expression also marks hemato cardiovascular cell lineages in differentiating embryonic stem (ES) cells, which may be used in transplantation decisions to treat cardiovascular diseases. Despite its developmental and clinical importance in cardiovascular tissues, the transcriptional regulatory system of Flk1 has remained unclear. Here, we report a novel enhancer of the mouse Flk1 gene directing early mesodermal expression during development as well as ES differentiation. The enhancer enriches various mesodermal progenitors, such as primitive erythropoietic progenitors, hemangioblast (BL-CFC) and cardiovascular progenitors (CV-CFC). The enhancer is activated by Bmp, Wnt and Fgf, and it contains Gata-, Cdx-, Tcf/Lef-, ER71/Etv2- and Fox-binding sites, some of which are bound specifically by each of these transcription factors. As these transcription factors are known to act under the control of the Bmp, Wnt and Fgf families, early Flk1 expression may be induced by cooperative interactions between Gata, Tcf/Lef, Cdx and ER71/Etv2 under the control of Bmp, Wnt and Fgf signaling. The enhancer is required for early Flk1 expression and for hemangioblast development during ES differentiation. PMID- 22071111 TI - Sexual and reproductive health status and related knowledge among female migrant workers in Guangzhou, China: a cross-sectional survey. AB - OBJECTIVE: The objective of this study was to investigate the current sexual and reproductive health (SRH) status including SRH-related knowledge and associated factors, self-reported symptoms of reproductive tract infection (RTI), medical assistance seeking behavior, sexual experience and contraceptive use, reproductive information approach and reproductive service utilization among female migrant workers in Huangpu district, Guangzhou city, China. STUDY DESIGN: A cross-sectional study was conducted in 2008 in eight factories, which were selected randomly from 32 eligible factories in the Huangpu district in Guangzhou. Descriptive statistics were used to describe the SRH status of migrant workers. Factors associated with the level of SRH knowledge were determined by a logistic regression model. RESULTS: Of 1346 female migrant workers, 831(61.7%) were unmarried and 515 (38.3%) were married. 27.2% of the unmarried respondents and 40.2% of the married respondents had suffered self-reported RTI symptoms. Among unmarried respondents, the median knowledge score was 5 points, compared to 8 points for the married. For unmarried migrant workers, factors associated with the knowledge level were age, education level, access to SRH information and service, sexual experiences and RTI symptoms. For married migrant workers, factors associated with the knowledge level were age, education level, access to SRH services and RTI symptoms. CONCLUSIONS: A high prevalence of self-reported RTI symptoms and a low knowledge level were found among young female migrant workers. Unmarried migrant workers are more vulnerable to SRH problems. Those findings demand more specific interventions targeting female migrants and in particular the unmarried. PMID- 22071110 TI - Six3 is required for ependymal cell maturation. AB - Ependymal cells are part of the neurogenic niche in the adult subventricular zone of the lateral ventricles, where they regulate neurogenesis and neuroblast migration. Ependymal cells are generated from radial glia cells during embryonic brain development and acquire their final characteristics postnatally. The homeobox gene Six3 is expressed in ependymal cells during the formation of the lateral wall of the lateral ventricles in the brain. Here, we show that Six3 is necessary for ependymal cell maturation during postnatal stages of brain development. In its absence, ependymal cells fail to suppress radial glia characteristics, resulting in a defective lateral wall, abnormal neuroblast migration and differentiation, and hydrocephaly. PMID- 22071112 TI - Evaluation of glycemic and oxidative/antioxidative status in the estradiol valerate-induced PCOS model of rats. AB - OBJECTIVE: The aim of this study was to show glycemic and oxidative/antioxidative status (GOAS) in rats with estradiol valerate (EV)-induced polycystic ovarian syndrome. STUDY DESIGN: Thirty mature female rats were randomly allocated to EV induced PCOS, sham and control groups. Malondialdehyde, catalase and fasting blood glucose levels were determined in order to evaluate GOAS. RESULTS: There was a statistically significant difference between PCOS and control groups (p<0.001) for hemolysate MDA while no difference was determined for either catalase or fasting blood glucose levels. On histopathological examination, the EV-induced PCOS group revealed disease-characteristic ovarian morphology. CONCLUSION: There was an increased compensation for oxidative stress by antioxidative biologic mechanisms in EV-induced PCOS rats. Interestingly, the sole result derived from this limited study is that the sesame oil+EV combination is not appropriate for the evaluation of oxidant-antioxidant status and also glycemic condition in PCOS. This study demonstrates the need for better designed experimental studies to elucidate the aetiopathogenesis of PCOS via novel techniques. PMID- 22071113 TI - Gene expression patterns of insulin-like growth factor 1, 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in human placenta from preterm deliveries: influence of additional factors. AB - OBJECTIVE: To compare patterns of human placental gene expression of IGF from pregnancies that ended with preterm delivery vs. full term pregnancies as controls. STUDY DESIGN: Real-time PCR was used to assess gene expression of IGF in human placental samples from 104 preterm and 140 full term pregnancies. RESULTS: In the preterm delivery group, the proportion of smokers was significantly higher than in the control group. A history of preterm delivery was more common in the preterm delivery group compared to the control group. In the preterm delivery group, placental samples showed an underexpression of the IGF-1 gene compared to controls. In cases of male fetal gender an overexpression of both the IGF-2 and the IGFBP-3 genes was observed. CONCLUSION: Among environmental factors influencing preterm delivery, smoking was the most significant in our study. In the majority of cases, preterm delivery was induced by intrauterine infection leading to a decreased activity of the IGF system. This mechanism may also play a role in the development of neurological sequelae and in decreased tolerance to fetal distress. The overexpression of the IGF-2 gene observed in the placenta with male fetal gender can be explained by its physiological role in the development of the male phenotype. PMID- 22071114 TI - Increased CXCL12 expression in the placentae of women with pre-eclampsia. AB - OBJECTIVE: To investigate the expression pattern of CXC chemokine ligand-12 (CXCL12) in the placentae of normal and pre-eclamptic women. STUDY DESIGN: Twenty five women with severe pre-eclampsia and 30 normotensive women, matched for gestational age, were enrolled in the study. Placental tissue from each woman was collected following delivery by caesarean section. Quantitative reverse transcription polymerase chain reaction, Western blot analysis and immunohistochemical staining were performed for mRNA expression, quantification and tissue localization of CXCL12 in each placenta. RESULTS: CXCL12 expression was greater in pre-eclamptic placentae compared with normal placentae. CXCL12 was detected in most placental tissue cells by immunohistochemical staining. CXCL12 immunoreactivity was significantly greater in syncytiotrophoblasts of pre eclamptic placentae compared with normal placentae. However, there was no significant difference in CXCL12 immunoreactivity in other tissues between the two groups. CONCLUSION: CXCL12 expression is significantly greater in the placentae of pre-eclamptic women compared with normal women. This may represent part of a compensatory mechanism for pre-eclampsia. PMID- 22071115 TI - Differential expression of Axin1, Cdc25c and Cdkn2d mRNA in 2-cell stage mouse blastomeres. AB - There is increasing evidence to show that 2-cell stage mouse blastomeres have differing developmental properties. Additionally, it has been suggested that such a difference might be due to their distribution of mRNA and/or protein asymmetry. However, to date, the exact genes that are involved in the orientation and order of blastomere division are not known. In this study, some differentially expressed transcripts were identified. Axin1, cell division cycle 25 homolog C (Cdc25c) and cyclin-dependent inhibitor 2D (Cdkn2d) were selected for validation by real-time polymerase chain reaction (PCR) based on published data. Our real time PCR results demonstrated that Axin1, Cdc25c and Cdkn2d genes had different levels of expression among blastomeres of the mouse 2-cell embryo i.e. the level of Axin1 mRNA was significantly higher in one blastomere when compared with the other blastomeres of the 2-cell embryo (p < 0.05). The variation in Cdc25c (p < 0.05) and Cdkn2d (p < 0.01) mRNA expression followed a similar trend to that of Axin1. In addition, the highest levels of expression of these three genes were detected in the same blastomere in the 2-cell embryo. We confirmed that there was an asymmetrical distribution pattern for Axin1, Cdc25c and Cdkn2d transcripts in 2-cell embryos. In conclusion, this study demonstrated clearly that there is embryonic asymmetry at the 2-cell stage and that these differentially expressed genes may result in differentiation in expression in embryo development. PMID- 22071116 TI - Examining the link between collision involvement and cocaine use. AB - BACKGROUND: Cocaine is one of the more commonly found illicit drugs in injured drivers. In this work, we examine the association between self-reported past year cocaine use and past year collision involvement in a large representative sample of adult drivers in Ontario. METHODS: Data are based on the CAMH Monitor, an ongoing cross-sectional telephone survey of Ontario adults aged 18 and older. Five years of data (2002, 2003, 2004, 2006, 2008) were merged for this study (N=8107) due to survey item availability. Logistic regression analysis was performed to identify the risk of self-reported collision involvement within the past 12 months associated with past year use of cocaine, while controlling for sociodemographic, driving exposure and drinking-driving (as a function of drinking status) factors. Due to listwise deletion, the logistic regression model was based on a reduced sample (N=7284). RESULTS: The prevalence of self-reported collision involvement within the past year was 18.9% among those who used cocaine in the past year compared to 7.4% of non-users. Logistic regression analysis, controlling for the potential confounding effects of age, gender, income, driving exposure and drinking-driving measures, found the odds of collision involvement in the preceding year among cocaine users was over twice that of non-users (OR=2.11, 95% CI=1.06-4.18). CONCLUSIONS: This study suggests that cocaine users are significantly more likely to report collision involvement in the past year. Additional work to confirm these observations, and to assess possible causal pathways, is needed. PMID- 22071117 TI - Motivators and barriers influencing willingness to participate in candidate HCV vaccine trials: perspectives of people who inject drugs. AB - BACKGROUND: A safe and efficacious vaccine may be the most efficient and cost effective strategy for controlling the hepatitis C virus (HCV) epidemic among people who inject drugs (PWID) and several candidates are in development. However, little is known about the factors that influence willingness to participate (WTP) in candidate HCV vaccine trials among this group. METHODS: HCV seronegative PWID recruited between 2008 and 2010 as part of a prospective observational cohort study in Sydney, Australia were asked whether they would be willing to participate in a future candidate hepatitis C vaccine trial and to provide reasons to explain their decision. RESULTS: Of 113 participants, 74% indicated WTP, 15% were unwilling to participate and 11% reported WTP that was contingent on vaccine characteristics and trial design issues. The most commonly reported motivator for hypothetical trial participation was altruism, followed by potential health benefits, financial remuneration, and knowledge gain. Barriers to hypothetical participation included fears about possible harms to health, such as concerns about vaccine safety, side effects, and acquiring HCV from the vaccine; other barriers included mistrust of biomedical research and time constraints. CONCLUSIONS: These results may be useful in designing strategies to enhance HCV vaccine trial recruitment and retention and have ethical implications for developing informed consent processes and standards of care. PMID- 22071118 TI - Ethnic-specific meta-analyses of association between the OPRM1 A118G polymorphism and alcohol dependence among Asians and Caucasians. AB - BACKGROUND: Many studies have investigated the association between the OPRM1 A118G polymorphism (rs1799971) and alcohol dependence, but the results were inconsistent. To better understand this relationship, ethnicity-specific meta analyses were conducted. METHODS: We retrieved all eligible studies published up to April 12, 2011 from the PubMed/MEDLINE, EMBASE, and ISI Web of Science databases. Ethnicity-specific meta-analyses were performed using either fixed- or random-effect models as appropriate. RESULTS: Twelve independent studies with 1900 cases and 2382 controls were included. Five studies were conducted in Asians and seven in Caucasians. Ethnicity-specific meta-analyses revealed that the A118G polymorphism was significantly associated with alcohol dependence risk in Asians (GA vs. AA: odds ratio [OR], 1.73; 95% confidence interval [CI], 1.33-2.25; GA+GG vs. AA: OR, 1.57; 95% CI, 1.22-2.02), but not in Caucasians (GA vs. AA: OR, 1.05; 95% CI, 0.75-1.49; GA+GG vs. AA: OR, 1.11; 95% CI, 0.79-1.55). CONCLUSIONS: The OPRM1 A118G polymorphism may contribute to the susceptibility of alcohol dependence in Asians but not in Caucasians. PMID- 22071119 TI - Piperazine compounds as drugs of abuse. AB - Synthetic drugs are among the most commonly abused drugs in the world. This abuse is widespread among young people, especially in the dance club and rave scenes. Over the last several years, piperazine derived drugs have appeared, mainly available via the internet, and sold as ecstasy pills or under the names of "Frenzy", "Bliss", "Charge", "Herbal ecstasy", "A2", "Legal X" and "Legal E". Although in the market piperazine designer drugs have the reputation of being safe, several experimental and epidemiological studies indicate risks for humans. Piperazine designer drugs can be divided into two classes, the benzylpiperazines such as N-benzylpiperazine (BZP) and its methylenedioxy analogue 1-(3,4 methylenedioxybenzyl)piperazine (MDBP), and the phenylpiperazines such as 1-(3 chlorophenyl)piperazine (mCPP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), and 1-(4-methoxyphenyl)piperazine (MeOPP). Toxicokinetic properties, including metabolic pathways, actions and effects in animals and humans, with some hypothesis of mechanism of action, and analytical approaches for the identification of these drugs are summarized in this review. PMID- 22071120 TI - Individual-level syringe coverage among Needle and Syringe Program attendees in Australia. AB - BACKGROUND: Harm associated with injecting drug use is a significant public health issue and a major cause of morbidity and mortality, with global estimates of 3 million injectors infected with HIV and 8 million living with chronic hepatitis C virus (HCV) infection. Estimates of program coverage are widely used in the context of HIV prevention and are critical in determining the effectiveness of interventions such as Needle and Syringe Programs (NSPs). METHODS: Data from a national cross-sectional study of NSP attendees in Australia were used to estimate individual-level syringe coverage as a proportion of monthly injections covered by a new syringe. Univariate and multivariate logistic regressions modelled associations between demographics, injecting risk, anti-HIV and HCV prevalence and syringe coverage. The median number of syringes retained per NSP attendee per annum was also estimated. RESULTS: Twenty percent of participants had insufficient new syringes for all injections. Syringe reuse (including reuse of one's own syringe) was independently associated with syringe coverage of <100%. Conversely, procurement of syringes from an NSP was independently associated with syringe coverage >=100%, with a greater protective effect occurring when NSP utilisation was combined with current engagement in opiate substitution therapy. The median number of syringes retained per participant per annum was 720, equivalent to 2 per day. CONCLUSIONS: While Australian NSP attendees report high syringe coverage by international standards, prevention efforts could be scaled up. Syringe reuse was associated with syringe coverage of <100%, suggesting the utility of reuse as a proxy for individual level syringe coverage. PMID- 22071121 TI - Patient satisfaction with methadone maintenance treatment: the relevance of participation in treatment and social functioning. AB - BACKGROUND: Patients' satisfaction with methadone maintenance treatment (MMT) is a key measure of treatment quality. The main objective of the present study is to identify independent factors that contribute significantly to satisfaction with MMT. METHOD: Participants were a representative sample of methadone-maintained patients (n=123) from the region of La Rioja. Satisfaction with MMT was assessed with the Verona Service Satisfaction Scale for Methadone Treatment (VSSS-MT), and mental health status with the General Health Questionnaire-28 (GHQ-28). Multivariate linear- and logistic-regression analyses were performed to identify variables independently associated with satisfaction with MMT. RESULTS: Multiple linear regression analysis revealed that the variables independently associated with VSSS-MT total score were number of hours per week that the centre dispensed methadone (beta=0.193), number of patients per centre (beta=0.233), perceived frequency of receiving information about methadone dose changes (beta=0.246), perceived influence on these changes (beta=0.194), and Social Dysfunction subscale of GHQ-28 (beta=-0.179). Multivariate binary logistic regression showed that the variables independently associated with the likelihood of being satisfied with MMT were number of years of education completed (OR=0.835), number of patients per centre (OR=1.009), perceived frequency of receiving information about methadone dose changes (OR=1.571), and Social Dysfunction subscale of GHQ 28 (OR=0.748). CONCLUSIONS: Patients from larger centres, who perceive themselves as participating to some extent in treatment decisions, and showing lower deterioration in social functioning are more likely to be satisfied with MMT. PMID- 22071122 TI - The relevance of age at first alcohol and nicotine use for initiation of cannabis use and progression to cannabis use disorders. AB - BACKGROUND: A younger age at onset of use of a specific substance is a well documented risk-factor for a substance use disorder (SUD) related to that specific substance. However, the cross-substance relationship between a younger age at onset of alcohol use (AU) and nicotine use (NU) and the risk of cannabis use disorders (CUD) in adolescence and early adulthood remains unclear. AIMS: To identify the sequence of and latency between initial AU/NU and initial cannabis use (CU). To investigate whether younger age at AU- and NU-onset is associated with any and earlier CU-onset and a higher risk of transition from first CU to CUD, taking into account externalizing disorders (ED) and parental substance use disorders as putative influential factors. METHODS: Prospective-longitudinal community study with N=3021 subjects (baseline age 14-24) and up to four assessment waves over up to ten years with additional direct parental and family history information. Substance use and CUD were assessed with the DSM-IV/M-CIDI. RESULTS: Most subjects with CU reported AU (99%) and NU (94%). Among users of both substances, 93% reported AU prior to CU (87% for NU). After adjustment for ED and parental substance use disorders younger age at AU-onset was associated with any CU. Younger age at NU-onset was associated with earlier CU initiation. Younger age at AU- and NU-onset was not associated with a higher risk of CUD. CONCLUSIONS: The cross-substance relevance of younger age at first AU and NU for the risk of CUD is limited to early CU involvement. PMID- 22071123 TI - Steroid and nonsteroidal anti-inflammatory drugs, cognitive decline, and dementia. AB - The aim of this study was to evaluate the effects of anti-inflammatory intake on cognitive function in 7234 community-dwelling elderly persons. Cognitive performance, clinical diagnosis of dementia, and anti-inflammatory use were evaluated at baseline, and 2, 4, and 7 years later. Multivariate logistic regression analyses were adjusted for sociodemographic, behavioral, physical, mental health variables, and genetic vulnerability (apolipoprotein E epsilon4). Elderly women taking inhaled corticosteroids were at increased risk for cognitive decline over 7 years in executive functioning (odds ratio, 1.76; 95% confidence interval, 1.14-2.71; p = 0.04); the effect being increased after continuous use (odds ratio, 3.15; 95% confidence interval, 1.29-7.68; p = 0.01) and not found after discontinuation of treatment. In men, no significant associations were observed. Corticosteroid use was not significantly associated with an increase risk of incident dementia over 7 years. Nonsteroidal anti-inflammatory drug use was not significantly associated with either dementia incidence or cognitive decline in both sexes. The association may be related to hypothalamic-pituitary adrenal corticotropic axis dysfunctioning rather than a direct anti-inflammatory mechanism. Long-term use of inhaled corticosteroids may constitute a form of reversible cognitive disorder in elderly women. Physicians should check this possibility before assuming neurodegenerative changes. PMID- 22071124 TI - The age-related deficit in LTP is associated with changes in perfusion and blood brain barrier permeability. AB - In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals. PMID- 22071125 TI - [Imported malaria and HIV infection in Madrid. Clinical and epidemiological features]. AB - INTRODUCTION: Few data are available in Spain data on human immunodeficiency virus (HIV) patients coinfected with malaria. This study has aimed to determine the epidemiological and clinical characteristics of imported malaria in patients coinfected with HIV. PATIENTS AND METHODS: A case-series retrospective study was performed using the patient's medical records. The study population consisted on patients diagnosed with malaria attended in our center from january 1, 2002 to december 31, 2007. RESULTS: A total of 484 episodes of malaria, 398 of which were included in this study, were identified. Co-infection with HIV was described in 32 cases. All of them occurred in individuals presumably with some degree of semi immunity. In the coinfected group, there were 13 cases (40.6%) asymptomatic, whereas this event occurred in 99 cases of patients not coinfected (37.2%) (P=0.707). The greater presence of anemia in co-infected patients (62.5% vs 32.3% in non-coinfected [P=0.001]) stands out. CONCLUSIONS: In present study, the clinical presentation forms were similar, regardless of the presence or absence of HIV infection. Although the study population does not reflect all possible scenarios of malaria and HIV coinfection, our results indicate the reality of patients attended in the Autonomous Community of Madrid. PMID- 22071126 TI - Performance of immunochromatographic and ELISA tests for detecting fallow deer infected with Mycobacterium bovis. AB - Fallow deer (Dama dama) are widely distributed as natural or naturalised populations, as well as in game parks and deer farms. We used 157 fallow deer sampled in populations considered to be Mycobacterium tuberculosis complex (MTC) free and 73 Mycobacterium bovis-infected fallow deer confirmed postmortem by culture to evaluate the diagnostic performance of two tests for the detection of anti-mycobacterial antibodies: the dual path platform (DPP) VetTB assay and the bovine purified protein derivative (bPPD) ELISA. We also compared their sensitivity with that of the skin test, analyzed the effect of haemolysis degree on the antibody detection and described the relationship between the test readings and presence/absence of gross tuberculosis (TB) compatible lesions. Sensitivity of bPPD ELISA was 51% at a specificity of 96%. Depending on the cut off value selected, the sensitivity of DPP VetTB ranged from 62 to 71%, while its specificity was 88-95%. In the subgroup of M. bovis-infected deer for which the skin test data were available (33 of 73); this method detected 76% of culture positive animals, although the specificity of the intradermal test was not determined in this study. When the DPP VetTB and skin test data were combined, the resulting sensitivity obtained in this sub-group of M. bovis-infected deer increased to 97%. Gross pathology identified TB compatible lesions (TBL) in 89% culture-confirmed fallow deer. The infected animals with visible lesions had significantly higher readings in the DPP VetTB, but not in the bPPD ELISA. Only high levels of haemolysis decreased antibody test sensitivity and this effect was more evident for the bPPD ELISA. The results allowed inferring a number of management recommendations for rapid detection of MTC infection in live fallow deer and in surveys on hunter-harvested cervids. PMID- 22071127 TI - Toxicity of hydroxylated alkyl-phenanthrenes to the early life stages of Japanese medaka (Oryzias latipes). AB - Polycyclic aromatic hydrocarbons (PAH) are hydrophobic environmental contaminants with petrogenic, biogenic, and pyrogenic sources. Alkylated PAH predominate in crude oils, are found in sediment downstream of pulp and paper mills, and can be more toxic than their non-alkylated homologues. The enzymatic metabolism of alkyl phenanthrenes generates ring and chain hydroxylated derivatives. The main objective of this research was to estimate the potential role of hydroxylation in PAH toxicity and secondly to better understand the relative risk of different PAH in complex mixtures. This project assessed the toxicity of ring and chain hydroxylated 1-methylphenanthrenes to the early life stages of Japanese medaka (Oryzias latipes). Phenols were more toxic than benzylic alcohols, and some phenols were more than four times more toxic than their non-hydroxylated counterpart. Ring hydroxylation can increase PAH toxicity, and metabolism may enhance alkyl-PAH toxicity through the generation of such metabolites. This paper is the first to describe the relative toxicity of a suite of hydroxylated alkyl PAH to the early life stages of fish, proposing an association between the preferential formation of para-quinones and enhanced toxicity. PMID- 22071128 TI - Marine n-3 fatty acids alter the proteomic response to methylmercury in Atlantic salmon kidney (ASK) cells. AB - Fish based diets have been linked to the amelioration of methylmercury (MeHg) induced symptoms in several epidemiological studies, particularly due to their contents of marine n-3 fatty acids. It has been suggested that n-3 fatty acids may mask the detrimental effects of MeHg due to their beneficial effect on the same biological functions which are negatively affected by MeHg. However, in vitro studies have implied that there may be direct interactions between the marine n-3 FAs and MeHg, which ameliorates MeHg toxicity through interactions at a biological level. To understand how marine n-3 FAs and MeHg interact in fish as a biological system, we wanted to investigate molecular interaction in a fish cell system. Atlantic salmon kidney (ASK) cells were pre-incubated with the marine n-3 FAs docosahexaenoic acid (22:6n-3, DHA) and eicosapentaenoic acid (20:5n-3, EPA) before exposing them to MeHg. Modulating effects of the marine FAs on MeHg toxicity were subsequently assessed using the exploratory technique of proteomics, in a factorial design. Thirty-four differentially regulated proteins were identified. From these; twenty-seven were shown to be differentially regulated by MeHg, twelve were regulated by the fatty acids, and another eight showed interaction effects between MeHg and the FAs. Several of the proteins were concomitantly affected by MeHg- and FA-main effects, as well as interaction effects. Functional annotations and pathway analysis of the proteins revealed that marine n-3 FAs and MeHg concurrently affected the abundance of protein markers relating to such molecular mechanisms as: cell signaling, calcium homeostasis, structural integrity, apoptosis, and energy metabolism. In conclusion, both marine n-3 FAs and MeHg can differentially affect the abundances of the same proteins, indicating modulating effects of EPA and DHA on MeHg metabolism, and possibly on its toxicity. PMID- 22071129 TI - Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications. AB - In the past decade, positron emission tomography (PET) with carbon-11-labeled Pittsburgh Compound B (PIB) has revolutionized the neuroimaging of aging and dementia by enabling in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer's disease (AD). Studies suggest that PIB-PET is sensitive for AD pathology, can distinguish AD from non-AD dementia (for example, frontotemporal lobar degeneration), and can help determine whether mild cognitive impairment is due to AD. Although the short half-life of the carbon-11 radiolabel has thus far limited the use of PIB to research, a second generation of tracers labeled with fluorine-18 has made it possible for amyloid PET to enter the clinical era. In the present review, we summarize the literature on amyloid imaging in a range of neurodegenerative conditions. We focus on potential clinical applications of amyloid PET and its role in the differential diagnosis of dementia. We suggest that amyloid imaging will be particularly useful in the evaluation of mildly affected, clinically atypical or early age-at-onset patients, and illustrate this with case vignettes from our practice. We emphasize that amyloid imaging should supplement (not replace) a detailed clinical evaluation. We caution against screening asymptomatic individuals, and discuss the limited positive predictive value in older populations. Finally, we review limitations and unresolved questions related to this exciting new technique. PMID- 22071130 TI - Edible oil adulterants, argemone oil and butter yellow, as aetiological factors for gall bladder cancer. AB - Carcinogenic potential of argemone oil (AO) and butter yellow (BY), the adulterants encountered in edible oil, in gall bladder of Swiss albino mice was undertaken to investigate the potential aetiological factors of gall bladder carcinoma (GBC) in the Indo-Gangetic basin. Twice weekly intraperitoneal (ip) administration of AO (5 ml/kg body wt) and BY (25 mg/kg body wt) to Swiss albino male and female mice for 30 and 60 days indicated that females were more vulnerable to these adulterants in terms of responses to inflammatory markers. Subsequent experiments with dietary exposure of AO (1%) and BY (0.06%) for 6 months in female mice showed symptoms related to cachexia, jaundice and anaemia. High levels of total cholesterol, low density lipoprotein (LDL), TG, bilirubin and low level of high density lipoprotein (HDL) as well as gallstone formation was shown by AO exposure only, leading to the development of adenocarcinoma. BY exposure resulted in adenoma and hyperplasia without stone formation. The cyclooxygenase (COX-2) overexpression was found to be related to prostaglandin E2 (PGE2) production in AO treated mice but not in BY exposed animals, thereby indicating a differential pathway specific carcinogenicity. PGE2 stimulates the secretion of secreted mucins (MUC5AC), which is involved in stone formation following AO exposure. Enhanced secretion of membrane bound mucins (MUC4) in BY and AO exposed mice resulted in the activation of ErbB2 and downstream signalling such as p-AKT, p-ERK and p-JNK, which ultimately affects the target proteins, p53 and p21 leading to adenoma and adenocarcinoma, respectively. The study suggests that AO and BY are responsible for producing GBC in mice along with stone formation in the AO exposed animals. PMID- 22071131 TI - The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer. AB - BACKGROUND: Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5 FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response. METHODS: PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer. RESULTS: Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104). CONCLUSION: These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours. PMID- 22071132 TI - Association of galectin-3 expression with melanoma progression and prognosis. AB - AIMS: Galectin-3 plays an important role in adhesion, proliferation, differentiation, angiogenesis and metastasis in multiple tumours. To investigate the role of galectin-3 in melanoma pathogenesis we examined the expression of galectin-3 in melanocytic lesions and analysed the correlation between galectin-3 expression and clinicopathologic factors including patient survival and BRAF mutation status. METHODS: We evaluated the expression of galectin-3 in 53 cases of benign naevi, 31 cases of dysplastic naevi, 59 in-situ melanomas, 314 cases of primary melanoma and 69 metastatic melanomas using tissue microarray and immunohistochemistry. RESULTS: Marked differences in expression of galectin-3 were seen between different categories of melanocytic lesions (ANOVA p<0.0001). An increase in expression of galectin-3 between benign naevi and thin primary melanomas and a progressive decrease in expression between thin primary melanomas and thicker melanomas or metastatic melanomas was seen. Strong galectin-3 expression was associated with improved overall survival (p=0.002 and p=0.0002 for cytoplasmic and nuclear expression, respectively) and melanoma-specific survival (p=0.017 and p=0.003 for cytoplasmic and nuclear expression, respectively). A multifactorial Cox regression analysis suggested that galectin-3 expression was an independent prognostic marker for overall survival in melanoma (risk ratio 0.73, 95% CI 0.547-0.970, p=0.031 for cytoplasmic expression and risk ratio 0.76, 95% CI 0.587-0.985, p=0.036 for nuclear expression). No association between galectin-3 expression and BRAF mutation status was observed. CONCLUSION: This study suggests that galectin-3 is a marker of progression in melanocytic lesions and a novel prognostic marker in primary melanoma. PMID- 22071133 TI - An algorithm to assess methodological quality of nutrition and mortality cross sectional surveys: development and application to surveys conducted in Darfur, Sudan. AB - BACKGROUND: Nutrition and mortality surveys are the main tools whereby evidence on the health status of populations affected by disasters and armed conflict is quantified and monitored over time. Several reviews have consistently revealed a lack of rigor in many surveys. We describe an algorithm for analyzing nutritional and mortality survey reports to identify a comprehensive range of errors that may result in sampling, response, or measurement biases and score quality. We apply the algorithm to surveys conducted in Darfur, Sudan. METHODS: We developed an algorithm based on internationally agreed upon methods and best practices. Penalties are attributed for a list of errors, and an overall score is built from the summation of penalties accrued by the survey as a whole. To test the algorithm reproducibility, it was independently applied by three raters on 30 randomly selected survey reports. The algorithm was further applied to more than 100 surveys conducted in Darfur, Sudan. RESULTS: The Intra Class Correlation coefficient was 0.79 for mortality surveys and 0.78 for nutrition surveys. The overall median quality score and range of about 100 surveys conducted in Darfur were 0.60 (0.12-0.93) and 0.675 (0.23-0.86) for mortality and nutrition surveys, respectively. They varied between the organizations conducting the surveys, with no major trend over time. CONCLUSION: Our study suggests that it is possible to systematically assess quality of surveys and reveals considerable problems with the quality of nutritional and particularly mortality surveys conducted in the Darfur crisis. PMID- 22071134 TI - Changes in free and bound fractions of aroma compounds of four Vitis vinifera cultivars at the last ripening stages. AB - The volatile composition of white Agudelo, Blancolexitimo, Godello and red Serradelo cultivars (NW Spain) harvested at two different stages of ripening have been evaluated. C(6)-compounds, alcohols, volatile fatty acids, monoterpenes, C(13)-norisoprenoids, volatile phenols and carbonyl compounds were identified and quantified in free and glycosidically bound forms by gas chromatography-mass spectrometry (GC-MS). The total volatile concentration showed a significant increase between the two ripening stages studied for all cultivars. The free volatile composition increased during maturity for Godello and Serradelo cultivars; however the glycosidically bound concentration increases for all cultivars with exception of B. lexitimo. Free C(6)-compounds ((E)-2-hexanal, 1 hexanol and (E)-2-hexen-1-ol) and bound alcohols (benzyl alcohol and 2 phenylethanol) showed the highest concentrations of volatile compounds for all grape cultivars in the two dates studied. Godello cultivar showed the highest change of volatile concentration between two ripening dates because of the high value of free C(6)-compounds. B. lexitimo was the most terpene-rich cultivar at the last ripening stage due to linalool; however C(13)-norisoprenoids in free form were detected in low concentrations for all cultivars but not in Godello and B. lexitimo cultivars at the last ripening stage. Free hexanoic acid increased during ripening in all cultivars. The evolution of volatiles during ripening of grape juice from the cultivars studied was not proportional to the changes in sugar content, which shows that the technological and aromatic maturities did not occur at the same time in these cultivars. The results also showed the cultivar * ripening date interaction for all, free and bound, groups of compounds. PMID- 22071135 TI - Cymatherelactone and cymatherols A-C, polycyclic oxylipins from the marine brown alga Cymathere triplicata. AB - An investigation of the oxylipin chemistry of the temperate brown alga Cymathere triplicata led to the isolation of several secondary metabolites, cymatherelactone (1) and cymatherols A-C (2-4), the latter as their methyl ester derivatives (5-7), which contained cyclopentyl, cyclopropyl, epoxide and lactone rings. Their structures were elucidated using a combination of spectroscopic techniques and synthetic chemistry. Cymatherelactone (1), as well as R- and S Mosher's esters of its seco acid, exhibited moderate sodium channel blocking activity. PMID- 22071136 TI - Chemical modifications of algal mannans and xylomannans: effects on antiviral activity. AB - The structures of two sulfated xylomannans extracted from the red alga Nemalion helminthoides were determined. These two fractions plus a sulfated mannan, isolated from the same alga and whose structure was previously reported, were subjected to chemical modification. The mannan was oversulfated with SO(3) pyridine in dimethyl sulfoxide at 60 degrees C during two and three hours and the xylomannans were subjected to Smith degradation in order to eliminate xylose side-chains. Structural analysis of all derivatives was carried out by methylation analysis and (13)C NMR spectroscopy. Antiviral activity against herpes simplex virus type 1 and 2, and dengue virus type 2 of native and modified mannans and xylomannans was estimated. Anticoagulant effect of the active fractions was also determined. PMID- 22071138 TI - Versatility and nuances of the architecture of haematopoiesis - Implications for the nature of leukaemia. AB - For many years there was a widely accepted picture of how a haematopoietic stem cell (HSC) gives rise to the multiple types of blood and immune cells. This described the general nature of stem and progenitor cells and the pathways of cell development. Recent years have seen many attempts to re-draw the map of haematopoiesis. These have become increasingly complex, and they often envisage multiples routes to some cell types. The 'established' view that self-renewal in haematopoiesis only occurs in HSCs has been challenged by the recognition of self renewing HSC-derived progenitor cells that display at least some fate restriction. This evolution of how normal haematopoiesis is viewed has inevitable implications for understanding the origins, disease progression and classification of the leukaemias. In essence, some progenitor cells are now seen as possessing a larger repertoire of routes to end-fates than was previously thought. This leads one to ask whether leukaemia stem cells are equally or less versatile than their normal counterparts? PMID- 22071137 TI - Comparative molecular analysis of therapy-related and de novo acute promyelocytic leukemia. AB - Therapy-related acute promyelocytic leukemia (t-APL) has been reported as a late complication of exposure to radiotherapy and/or chemotherapeutic agents targeting DNA topoisomerase II. We have analyzed in t-APL novel gene mutations recently associated with myeloid disorders. Unlike previous reports in acute myeloid leukemia (AML), our results showed neither IDHs nor TET2 mutations in t-APL. However we found an R882H mutation in the DNMT3A gene in a patient with t-APL suggesting a possible role of this alteration in the pathogenesis of t-APL. PMID- 22071139 TI - Older patients with normal karyotype acute myeloid leukemia have a higher rate of genomic changes compared to young patients as determined by SNP array analysis. AB - Older patients with AML have a worse outcome compared to young patients. To study for potential contributors to their poor prognosis, we compared two NK-AML cohorts, young (< 60 years old) and old (>= 60 years old), via high density SNP array analysis. Older patients had more genomic changes (1.83 +/- 0.23 vs. 1.16 +/- 0.2, p=0.037) and a trend for a higher number of copy number neutral loss of heterozygosity (0.5 +/- 0.2 vs. 0.24 +/- 0.08, p=0.088) compared to young patients. We speculate that complex genomic changes in NK-AML may be a sign of an increase in genomic instability and an indicator of a worse prognosis. PMID- 22071140 TI - Unrelated cord blood transplantation in adolescent and young adults with hematologic malignancies. PMID- 22071143 TI - Chondrogenesis and cartilage tissue engineering: the longer road to technology development. AB - Joint injury and disease are painful and debilitating conditions affecting a substantial proportion of the population. The idea that damaged cartilage in articulating joints might be replaced seamlessly with tissue-engineered cartilage is of obvious commercial interest because the market for such treatments is large. Recently, a wealth of new information about the complex biology of chondrogenesis and cartilage has emerged from stem cell research, including increasing evidence of the role of physical stimuli in directing differentiation. The challenge for the next generation of tissue engineers is to identify the key elements in this new body of knowledge that can be applied to overcome current limitations affecting cartilage synthesis in vitro. Here we review the status of cartilage tissue engineering and examine the contribution of stem cell research to technology development for cartilage production. PMID- 22071144 TI - Effect of membranes with various hydrophobic/hydrophilic properties on lipase immobilized activity and stability. AB - In this study, three membranes: regenerated cellulose (RC), glass fiber (GF) and polyvinylidene fluoride (PVDF), were grafted with 1,4-diaminobutane (DA) and activated with glutaraldehyde (GA) for lipase covalent immobilization. The efficiencies of lipases immobilized on these membranes with different hydrophobic/hydrophilic properties were compared. The lipase immobilized on hydrophobic PVDF-DA-GA membrane exhibited more than an 11-fold increase in activity compared to its immobilization on a hydrophilic RC-DA-GA membrane. The relationship between surface hydrophobicity and immobilized efficiencies was investigated using hydrophobic/hydrophilic GF membranes which were prepared by grafting a different ratio of n-butylamine/1,4-diaminobutane (BA/DA). The immobilized lipase activity on the GF membrane increased with the increased BA/DA ratio. This means that lipase activity was exhibited more on the hydrophobic surface. Moreover, the modified PVDF-DA membrane was grafted with GA, epichlorohydrin (EPI) and cyanuric chloride (CC), respectively. The lipase immobilized on the PVDF-DA-EPI membrane displayed the highest specific activity compared to other membranes. This immobilized lipase exhibited more significant stability on pH, thermal, reuse, and storage than did the free enzyme. The results exhibited that the EPI modified PVDF is a promising support for lipase immobilization. PMID- 22071145 TI - Breast cancer: current state and future promise. PMID- 22071146 TI - DNA polymerase MU is a global player in the repair of non-homologous end-joining substrates. AB - The specialized DNA polymerase MU (pol MU) intervenes in the repair mechanism non homologous end-joining (NHEJ) as an end-processing factor but its role has not been fully elucidated. Pol MU has been shown to participate in DNA synthesis at junctions in vitro, including on unpaired substrates, and to promote annealing. However, the phenotypes observed in vivo poorly recapitulate the functions of pol MU reported in vitro. We analysed the repair of DNA double-strand breaks (DSBs) in a cellular context using improved NHEJ substrates. These substrates do not replicate in mammalian cells, thereby result in clonal repair events, which allows the measure of the efficiency of repair. We validated this paradigm by comparing the repair of NHEJ substrates to the repair reported for chromosome DSBs in mouse cells. Molecular analysis and, in most cases sequencing of more than 1500 repair events on a variety of NHEJ substrates in wild type and pol MU( /-) mouse embryonic fibroblasts shows that, unexpectedly, the absence of pol MU decreases the efficiency of joining of all types of DSBs, including those that do not undergo end-processing. Importantly, by reducing the efficiency of accurate events, lack of pol MU also affects the overall fidelity of the repair process. We also show that, although pol MU does not help protect DNA ends from resection, the efficiency of repair of resected ends is reduced in the absence of pol MU. Interestingly, the DNA synthesis activity of pol MU, including on non-aligned substrates, appears negligible at least in a cellular context. Our data point to a critical role for pol MU as a global repair player that increases the efficiency and the fidelity of NHEJ. PMID- 22071148 TI - DNA damage research in China. PMID- 22071147 TI - The kinetochore protein Bub1 participates in the DNA damage response. AB - The DNA damage response (DDR) and the spindle assembly checkpoint (SAC) are two critical mechanisms by which mammalian cells maintain genome stability. There is a growing body of evidence that DDR elements and SAC components crosstalk. Here we report that Bub1 (budding uninhibited by benzimidazoles 1), one of the critical kinetochore proteins essential for SAC, is required for optimal DDRs. We found that knocking-down Bub1 resulted in prolonged H2AX foci and comet tail formation as well as hypersensitivity in response to ionizing radiation (IR). Further, we found that Bub1-mediated Histone H2A Threonine 121 phosphorylation was induced after IR in an ATM-dependent manner. We demonstrated that ATM phosphorylated Bub1 on serine 314 in response to DNA damage in vivo. Finally, we showed that ATM-mediated Bub1 serine 314 phosphorylation was required for IR induced Bub1 activation and for the optimal DDR. Together, we elucidate the molecular mechanism of DNA damage-induced Bub1 activation and highlight a critical role of Bub1 in DDR. PMID- 22071149 TI - Defects in DNA degradation revealed in crystal structures of TREX1 exonuclease mutations linked to autoimmune disease. AB - Mutations within the human TREX1 3' exonuclease are associated with Aicardi Goutieres Syndrome (AGS) and familial chilblain lupus (FCL). Both AGS and FCL are autoimmune diseases that result in increased levels of interferon alpha and circulating antibodies to DNA. TREX1 is a member of the endoplasmic reticulum (ER)-associated SET complex and participates in granzyme A-mediated cell death to degrade nicked genomic DNA. The loss of TREX1 activity may result in the accumulation of double-stranded DNA (dsDNA) degradation intermediates that trigger autoimmune activation. The X-ray crystal structures of the TREX1 wt apoprotein, the dominant D200H, D200N and D18N homodimer mutants derived from AGS and FCL patients, as well as the recessive V201D homodimer mutant have been determined. The structures of the D200H and D200N mutant proteins reveal the enzyme has lost coordination of one of the active site metals, and the catalytic histidine (H195) is trapped in a conformation pointing away from the active site. The TREX1 D18N and V201D mutants are able to bind both metals in the active site, but with inter-metal distances that are larger than optimal for catalysis. Additionally, all of the mutant structures reveal a reduced mobility in the catalytic histidine, providing further explanation for the loss of catalytic activity. The structures of the mutant TREX1 proteins provide insight into the dysfunction relating to human disease. Additionally, the TREX1 apoprotein structure together with the previously determined wild type substrate and product structures allow us to propose a distinct mechanism for the TREX1 exonuclease. PMID- 22071150 TI - Reversibility of replicative senescence in Saccharomyces cerevisiae: effect of homologous recombination and cell cycle checkpoints. AB - Primary human somatic cells grown in culture divide a finite number of times, exhibiting progressive changes in metabolism and morphology before cessation of cycling. This telomere-initiated cellular senescence occurs because cells have halted production of telomerase, a DNA polymerase required for stabilization of chromosome ends. Telomerase-deficient Saccharomyces cerevisiae cells undergo a similar process, with most cells arresting growth after approximately 60 generations. In the current study we demonstrate that senescence is largely reversible. Reactivation of telomerase (EST2) expression in the growth-arrested cells led to resumption of cycling and reversal of senescent cell characteristics. Rescue was also observed after mating of senescent haploid cells with telomerase-proficient cells to form stable diploids. Although senescence was reversible in DNA damage checkpoint response mutants (mec3 and/or rad24 cells), survival of recombination-defective rad52 mutants remained low after telomerase reactivation. Telomere lengths in rescued est2 cells were initially half those of wildtype cells, but could be restored to normal by propagation for ~70 generations in the presence of telomerase. These results place limitations on possible models for senescence and indicate that most cells, despite gross morphological changes and short, resected telomeres, do not experience lethal DNA damage and become irreversibly committed to death. PMID- 22071151 TI - [Jugal swelling revealing acute lymphoblastic leukemia]. AB - INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. The clinical presentation at diagnosis is due to bone marrow infiltration or extra-medullary involvement. Maxillofacial localization is very rare in ALL. We report a case of T-ALL revealed by right cheek swelling in a 14-year-old boy. CASE PRESENTATION: A 14-year-old boy had presented with a 6 cm right cheek swelling for two months, complicated by pyrexia, cervical adenopathy, and splenomegaly. CT scan revealed a 3*7*8 cm swelling surrounded by voluminous sub chin, subclavicular, mediastinal, and paratracheal bilateral adenopathies. The biological analyses revealed normocytic anemia, hyperleukocytosis with 83.6% blast cells, neutropenia, and thrombopenia. The biopsy histology and the immuno histochemical analysis suggested a diffuse small-cell Non-Hodgkin lymphoma (NHL). The myelogram identified a type 1 ALL and immunophenotyping on bone marrow cells suggested phenotype T ALL. The patient was treated according to the MARALL-06 protocol and died on the 17th day of induction, in septic shock. DISCUSSION: Despite their rare occurrence, ALL should be included in the differential diagnosis of jugal swelling. The evident hematological context should suggest the diagnosis and a myelogram should be performed as soon as possible because the outcome is rapidly fatal. PMID- 22071152 TI - Paramedic electrocardiogram and rhythm identification: a convenient training device. AB - INTRODUCTION: A common reason for utilizing local paramedics and the emergency medical services is for the recognition and immediate treatment of chest pain, a complaint that has multiple possible etiologies. While many of those complaining of disease processes responsible for chest pain are benign, some will be life threatening and will require immediate identification and treatment. The ability of paramedics to not only perform field electrocardiograms (ECGs), but to accurately diagnose various unstable cardiac rhythms has shown significant reduction in time to specific treatments. Increasing the overall accuracy of ECG interpretation by paramedics has the potential to facilitate early and appropriate treatment and decrease patient morbidity and mortality. METHODS: A convenient training device (flip book) on ambulances and in common areas in the fire station could improve field interpretation of certain cardiac rhythms. This training device consists of illustrated sample ECG tracings and their associated diagnostic criteria. The goal was to enhance the recognition and interpretation of ECGs, and thereby, reduce delays in the initiation of treatment and potential complications associated with misinterpretation.This study was a prospective, observational study using a matched pre-test/post-test design. The study period was from November 2008 to December 2008. A total of 136 paramedics were approached to participate in this study. A pre-test consisting of 15 12-lead ECGs was given to all paramedics who agreed to participate in the study. Once the pre tests were completed, the flip books were placed in common areas. Approximately one month after the flip books were made available to the paramedics, a post-test was administered.Statistical comparisons were made between the pre- and post-test scores for both the global test and each type of rhythm. RESULTS: Using these data, there were no statistically significant improvements in the global ECG interpretation or on individual rhythm interpretations. CONCLUSIONS: A flip book with multiple ECG rhythms and definitions without the benefit of any outside support was not effective in improving paramedic identification of ECG rhythms on a post-test. Suggestions for further research include repeating the study with a larger sample size; utilizing a lecturer to explain how to use the flip book in the most efficient manner; reiterating how to read and interpret ECGs; and answering questions. Comparing test scores of paramedic students, and newly certified paramedics as opposed to veteran paramedics also may indicate that the flip books are more suited for one group over another. PMID- 22071153 TI - The role of co-activation in strength and force modulation in the elbow of children with unilateral cerebral palsy. AB - To study the role of coactivation in strength and force modulation in the elbow joint of children and adolescents with cerebral palsy (CP), we investigated the affected and contralateral arm of 21 persons (age 8-18) with spastic unilateral CP in three tasks: maximal voluntary isokinetic concentric contraction and passive isokinetic movement during elbow flexion and extension, and sub-maximal isometric force tracing during elbow flexion. Elbow flexion-extension torque and surface electromyography (EMG) of the biceps brachii (BB) and triceps brachii (TB) muscles were recorded. During the maximal contractions, the affected arm was weaker, had decreased agonist and similar antagonist EMG amplitudes, and thus increased antagonist co-activation (% of maximal activity as agonist) during both elbow flexion and extension, with higher coactivation levels of the TB than the BB. During passive elbow extension, the BB of the affected arm showed increased resistance torque and indication of reflex, and thus spastic, activity. No difference between the two arms was found in the ability to modulate force, despite increased TB coactivation in the affected arm. The results indicate that coactivation plays a minor role in muscle weakness in CP, and does not limit force modulation. Moreover, spasticity seems particularly to increase coactivation in the muscle antagonistic to the spastic one, possibly in order to increase stability. PMID- 22071154 TI - Glucoprivation in the ventrolateral medulla decreases brown adipose tissue sympathetic nerve activity by decreasing the activity of neurons in raphe pallidus. AB - In urethane/alpha-chloralose anesthetized rats, cold exposure increased brown adipose tissue sympathetic nerve activity (BAT SNA: +699 +/- 104% control). Intravenous administration of 2-deoxy-D-glucose (2-DG; 200 mg.ml(-1).kg(-1)) reversed the cold-evoked activation of BAT SNA (nadir: 139 +/- 36% of control) and decreased BAT temperature (-1.1 +/- 0.2 degrees C), expired CO(2) (-0.4 +/- 0.1%), and core temperature (-0.5 +/- 0.0). Similarly, unilateral nanoinjection of the glucoprivic agent 5-thioglucose (5-TG; 12 MUg/100 nl) in the ventrolateral medulla (VLM) completely reversed the cold-evoked increase in BAT SNA (nadir: 104 +/- 7% of control), and decreased T(BAT) (-1.4 +/- 0.3 degrees C), expired CO(2) (-0.2 +/- 0.0%), and heart rate (-35 +/- 10 beats/min). The percentage of rostral raphe pallidus (RPa)-projecting neurons in the dorsal hypothalamic area/dorsomedial hypothalamus that expressed Fos in response to cold exposure (ambient temperature: 4-10 degrees C) did not differ between saline (28 +/- 6%) and 2-DG (30 +/- 5%) pretreated rats, whereas the percentage of spinally projecting neurons in the RPa/raphe magnus that expressed Fos in response to cold exposure was lower in 2-DG- compared with saline-pretreated rats (22 +/- 6% vs. 42 +/- 5%, respectively). The increases in BAT SNA evoked by nanoinjection of bicuculline in the RPa or by transection of the neuraxis at the pontomedullary border were resistant to inhibition by glucoprivation. These results suggest that neurons within the VLM play a role in the glucoprivic inhibition of BAT SNA and metabolism, that this inhibition requires neural structures rostral to the pontomedullary border, and that this inhibition is mediated by a GABAergic input to the RPa. PMID- 22071155 TI - L-arginine supplementation abolishes the blood pressure and endothelin response to chronic increases in plasma sFlt-1 in pregnant rats. AB - While soluble fms-like tyrosine kinase-1 (sFlt-1) and endothelin-1 (ET-1) have been implicated in the pathogenesis of preeclampsia (PE), the mechanisms whereby increased sFlt-1 leads to enhanced ET-1 production and hypertension remain unclear. It is well documented that nitric oxide (NO) production is reduced in PE; however, whether a reduction in NO synthesis plays a role in increasing ET-1 and blood pressure in response to chronic increases in plasma sFlt-1 remains unclear. The purpose of this study was to determine the role of reduced NO synthesis in the increase in blood pressure and ET-1 in response to sFlt-1 in pregnant rats. sFlt-1 was infused into normal pregnant (NP) Sprague-Dawley rats (3.7 MUg.kg(-1).day(-1) for 6 days beginning on day 13 of gestation) treated with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (100 mg/l for 4 days) or supplemented with 2% L-Arg (in drinking water for 6 days beginning on day 15 of gestation). Infusion of sFlt-1 into NP rats significantly elevated mean arterial pressure compared with control NP rats: 116 +/- 2 vs. 103 +/- 1 mmHg (P < 0.05). NO synthase inhibition had no effect on the blood pressure response in sFlt-1 hypertensive pregnant rats (121 +/- 3 vs. 116 +/- 2 mmHg), while it significantly increased mean arterial pressure in NP rats (128 +/- 4 mmHg, P < 0.05). In addition, NO production was reduced ~70% in isolated glomeruli from sFlt-1 hypertensive pregnant rats compared with NP rats (P < 0.05). Furthermore, prepro-ET-1 in the renal cortex was increased ~3.5-fold in sFlt-1 hypertensive pregnant rats compared with NP rats. Supplementation with L-Arg decreased the sFlt-1 hypertension (109 +/- 3 mmHg, P < 0.05) but had no effect on the blood pressure response in NP rats (109 +/- 3 mmHg) and abolished the enhanced sFlt-1 induced renal cortical prepro-ET expression. In conclusion, a reduction in NO synthesis may play an important role in the enhanced ET-1 production in response to sFlt-1 hypertension in pregnant rats. PMID- 22071156 TI - The physiology and pathophysiology of the neural control of the counterregulatory response. AB - Despite significant technological and pharmacological advancements, insulin replacement therapy fails to adequately replicate beta-cell function, and so glucose control in type 1 diabetes mellitus (T1D) is frequently erratic, leading to periods of hypoglycemia. Moreover, the counterregulatory response (CRR) to falling blood glucose is impaired in diabetes, leading to an increased risk of severe hypoglycemia. It is now clear that the brain plays a significant role in the development of defective glucose counterregulation and impaired hypoglycemia awareness in diabetes. In this review, the basic intracellular glucose-sensing mechanisms are discussed, as well as the neural networks that respond to and coordinate the body's response to a hypoglycemic challenge. Subsequently, we discuss how the body responds to repeated hypoglycemia and how these adaptations may explain, at least in part, the development of impaired glucose counterregulation in diabetes. PMID- 22071157 TI - Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs. AB - During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [D-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [D-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin. PMID- 22071159 TI - Biological and analytical variation of the human sweating response: implications for study design and analysis. AB - Appropriate quantification of analytical and biological variation of thermoregulatory sweating has important practical utility for research design and statistical analysis. We sought to examine contributors to variability in local forearm sweating rate (SR) and sweating onset (SO) and to evaluate the potential for using bilateral measurements. Two women and eight men (26 +/- 9 yr; 79 +/- 12 kg) completed 5 days of heat acclimation and walked (1.8 l/min VO(2)) on three occasions for 30 min in 40 degrees C, 20% RH, while local SR and SO were measured. Local SR measures among days were not different (2.14 +/- 0.72 vs. 2.02 +/- 0.79 vs. 2.31 +/- 0.72 mg.cm(2).min(-1), P = 0.19) nor was SO (10.47 +/- 2.54 vs. 10.04 +/- 2.97 vs. 9.87 +/- 3.44 min P = 0.82). Bilateral SR (2.14 +/- 0.72 vs. 2.16 +/- 0.71 mg.cm(2).min(-1), P = 0.56) and SO (10.47 +/- 2.54 vs. 10.83 +/ 2.48 min, P = 0.09) were similar and differences were <= 1 SD of day-to-day differences for a single forearm. Analytical imprecision (CV(a)), within (CV(i)) , and between (CV(g))-subjects' coefficient of variation for local SR were 2.4%, 22.3%, and 56.4%, respectively, and were 0%, 9.6%, and 41%, respectively, for SO. We conclude: 1) technologically, sweat capsules contribute negligibly to sweat measurement variation; 2) bilateral measures of SR and SO appear interchangeable; 3) when studying potential factors affecting sweating, changes in SO afford a more favorable signal-to-noise ratio vs. changes in SR. These findings provide a quantitative basis for study design and optimization of power/sample size analysis in the evaluation of thermoregulatory sweating. PMID- 22071158 TI - Heme oxygenase, a novel target for the treatment of hypertension and obesity? AB - Heme oxygenase (HO) is the rate-limiting enzyme in the metabolism of heme releasing bioactive molecules carbon monoxide (CO), biliverdin, and iron, each with beneficial cardiovascular actions. Biliverdin is rapidly reduced to bilirubin, a potent antioxidant, by the enzyme biliverdin reductase, and iron is rapidly sequestered by ferritin in the cell. Several studies have demonstrated that HO-1 induction can attenuate the development of hypertension as well as lower blood pressure in established hypertension in both genetic and experimental models. HO-1 induction can also reduce target organ injury and can be beneficial in cardiovascular diseases, such as heart attack and stroke. Recent studies have also identified a beneficial role for HO-1 in the regulation of body weight and metabolism in diabetes and obesity. Chronic HO-1 induction lowers body weight and corrects hyperglycemia and hyperinsulinemia. Chronic HO-1 induction also modifies the phenotype of adipocytes in obesity from one of large, cytokine producing to smaller, adiponectin producing. Finally, chronic induction of HO-1 increases oxygen consumption, CO(2), and heat production and activity in obese mice. This review will discuss the current understanding of the actions of the HO system to lower blood pressure and body weight and how HO or its metabolites may be ideal candidates for the development of drugs that can both reduce blood pressure and lower body weight. PMID- 22071160 TI - Adipocyte-specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice. AB - Previous studies demonstrated that overexpression of angiotensinogen (AGT) in adipose tissue increased blood pressure. However, the contribution of endogenous AGT in adipocytes to the systemic renin-angiotensin system (RAS) and blood pressure control is undefined. To define a role of adipocyte-derived AGT, mice with loxP sites flanking exon 2 of the AGT gene (Agt(fl/fl)) were bred to transgenic mice expressing Cre recombinase under the control of an adipocyte fatty acid-binding protein 4 promoter (aP2) promoter to generate mice with adipocyte AGT deficiency (Agt(aP2)). AGT mRNA abundance in adipose tissue and AGT secretion from adipocytes were reduced markedly in adipose tissues of Agt(aP2) mice. To determine the contribution of adipocyte-derived AGT to the systemic RAS and blood pressure control, mice were fed normal laboratory diet for 2 or 12 mo. In males and females of each genotype, body weight and fat mass increased with age. However, there was no effect of adipocyte AGT deficiency on body weight, fat mass, or adipocyte size. At 2 and 12 mo of age, mice with deficiency of AGT in adipocytes had reduced plasma concentrations of AGT (by 24-28%) compared with controls. Moreover, mice lacking AGT in adipocytes exhibited reduced systolic blood pressures compared with controls (Agt(fl/fl), 117 +/- 2; Agt(aP2), 110 +/- 2 mmHg; P < 0.05). These results demonstrate that adipocyte-derived AGT contributes to the systemic RAS and blood pressure control. PMID- 22071161 TI - Clenbuterol, a beta2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle. AB - Clenbuterol, a beta2-adrenergic agonist, reduces mitochondrial content and enzyme activities in skeletal muscle, but the mechanism involved has yet to be identified. We examined whether clenbuterol-induced changes in the muscles' metabolic profile and the intrinsic capacity of mitochondria to oxidize substrates are associated with reductions in the nuclear receptor coactivator PGC 1 alpha and/or an increase in the nuclear corepressor RIP140. In rats, clenbuterol was provided in the drinking water (30 mg/l). In 3 wk, this increased body (8%) and muscle weights (12-17%). In red (R) and white (W) muscles, clenbuterol induced reductions in mitochondrial content (citrate synthase: R, 27%; W, 52%; cytochrome-c oxidase: R, 24%; W, 34%), proteins involved in fatty acid transport (fatty acid translocase/CD36: R, 36%; W, 35%) and oxidation [beta hydroxyacyl CoA dehydrogenase (beta-HAD): R, 33%; W, 62%], glucose transport (GLUT4: R, 8%; W, 13%), lactate transport monocarboxylate transporter (MCT1: R, 61%; W, 37%), and pyruvate oxidation (PDHE1alpha, R, 18%; W, 12%). Concurrently, only red muscle lactate dehydrogenase activity (25%) and MCT4 (31%) were increased. Palmitate oxidation was reduced in subsarcolemmal (SS) (R, 30%; W, 52%) and intermyofibrillar (IMF) mitochondria (R, 17%; W, 44%) along with reductions in beta-HAD activity (SS: R, 17%; W, 51%; IMF: R, 20%; W, 57%). Pyruvate oxidation was only reduced in SS mitochondria (R, 20%; W, 28%), but this was not attributable solely to PDHE1alpha, which was reduced in both SS (R, 21%; W, 20%) and IMF mitochondria (R, 15%; W, 43%). These extensive metabolic changes induced by clenbuterol were associated with reductions in PGC-1alpha (R, 37%; W, 32%) and increases in RIP140 (R, 23%; W, 21%). This is the first evidence that clenbuterol appears to exert its metabolic effects via simultaneous and reciprocal changes in the nuclear receptor coactivator PGC-1alpha and the nuclear corepressor RIP140. PMID- 22071162 TI - Experimental mild renal insufficiency mediates early cardiac apoptosis, fibrosis, and diastolic dysfunction: a kidney-heart connection. AB - Impaired renal function with loss of nephron number in chronic renal disease (CKD) is associated with increased cardiovascular morbidity and mortality. However, the structural and functional cardiac response to early and mild reduction in renal mass is poorly defined. We hypothesized that mild renal impairment produced by unilateral nephrectomy (UNX) would result in early cardiac fibrosis and impaired diastolic function, which would progress to a more global left ventricular (LV) dysfunction. Cardiorenal function and structure were assessed in rats at 4 and 16 wk following UNX or sham operation (Sham); (n = 10 per group). At 4 wk, blood pressure (BP), aldosterone, glomerular filtration rate (GFR), proteinuria, and plasma B-type natriuretic peptide (BNP) were not altered by UNX, representing a model of mild early CKD. However, UNX was associated with significantly greater LV myocardial fibrosis compared with Sham. Importantly, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed increased apoptosis in the LV myocardium. Further, diastolic dysfunction, assessed by strain echocardiography, but with preserved LVEF, was observed. Changes in genes related to the TGF-beta and apoptosis pathways in the LV myocardium were also observed. At 16 wk post-UNX, we observed persistent LV fibrosis and impairment in LV diastolic function. In addition, LV mass significantly increased, as did LVEDd, while there was a reduction in LVEF. Aldosterone, BNP, and proteinuria were increased, while GFR was decreased. The myocardial, structural, and functional alterations were associated with persistent changes in the TGF-beta pathway and even more widespread changes in the LV apoptotic pathway. These studies demonstrate that mild renal insufficiency in the rat results in early cardiac fibrosis and impaired diastolic function, which progresses to more global LV remodeling and dysfunction. Thus, these studies importantly advance the concept of a kidney-heart connection in the control of myocardial structure and function. PMID- 22071163 TI - Editorial focus: A fat contribution to RAS activation and blood pressure control: evidence from angiotensinogen conditional null mice. Focus on: "Adipocyte specific deficiency of angiotensinogen decreases plasma angiotensinogen concentration and systolic blood pressure in mice.". PMID- 22071164 TI - Validation of the Symptom and Problem Checklist of the German Hospice and Palliative Care Evaluation (HOPE). AB - CONTEXT: The German Hospice and Palliative Care Evaluation (HOPE) is a national, long-term quality assurance project. Every year, German hospice and palliative care institutions document a core data set for their patients for a period of three months. OBJECTIVES: To validate the multidimensional symptom and problem checklist (HOPE-SP-CL) of the core data set and report details on reliability and validity. METHODS: Data from yearly evaluation periods between 2002 and 2009 were used to calculate construct and convergent validity, internal consistency, test retest reliability, and documentation discipline and acceptance of the core documentation system. RESULTS: The HOPE-SP-CL includes items on physical, nursing, psychological, and social symptoms and problems. Factor analysis extracted four low to moderately intercorrelating factors with eigenvalues greater than 1.0 explaining 56% of the total variance. Discriminant validity of the HOPE-SP-CL showed good properties in detecting patient groups with different symptom intensities and overall symptom burden using the Eastern Cooperative Oncology Group performance status and primary cancer diagnosis as external validation criteria. The global sum score of the HOPE-SP-CL correlated most closely with the Palliative Outcome Scale staff version (r=0.750). Internal consistencies ranged between alpha=0.768-0.801 at three different times of assessment. Test-retest coefficients showed moderate to high correlations at one week intervals. CONCLUSION: Analyses of reliability and validity of the HOPE-SP CL showed satisfactory to good psychometric properties; therefore, the HOPE-SP-CL can be recommended for standard implementation in German hospice and palliative care institutions. PMID- 22071165 TI - Self-compassion in patients with persistent musculoskeletal pain: relationship of self-compassion to adjustment to persistent pain. AB - CONTEXT: Self-compassion entails qualities such as kindness and understanding toward oneself in difficult circumstances and may influence adjustment to persistent pain. Self-compassion may be a particularly influential factor in pain adjustment for obese individuals who suffer from persistent pain, as they often experience heightened levels of pain and lower levels of psychological functioning. OBJECTIVES: The purpose of the present study was to examine the relationship of self-compassion to pain, psychological functioning, pain coping, and disability among patients who have persistent musculoskeletal pain and who are obese. METHODS: Eighty-eight obese patients with persistent pain completed a paper-and-pencil self-report assessment measure before or after their appointment with their anesthesiologist. RESULTS: Hierarchical linear regression analyses demonstrated that even after controlling for important demographic variables, self-compassion was a significant predictor of negative affect (beta=-0.48, P<0.001), positive affect (beta=0.29, P=0.01), pain catastrophizing (beta=-0.32, P=0.003), and pain disability (beta=-0.24, P<0.05). CONCLUSION: The results of this study indicate that self-compassion may be important in explaining the variability in pain adjustment among patients who have persistent musculoskeletal pain and are obese. PMID- 22071166 TI - Impact of infections on the survival of hospitalized advanced cancer patients. AB - CONTEXT: Advanced cancer patients remain highly susceptible to infections, leading to significant morbidity and mortality. A lack of consensus on the management of infections in this population stems from the heterogeneity of the patient group, divergent goals of care, and unknown prognosis with antibiotic treatment. OBJECTIVES: This prospective single cohort study examined the impact of infection and its treatment on the survival of hospitalized advanced cancer patients compared with a similar cohort without infection. METHODS: A total of 441 patients were referred to the palliative care (PC) consult service in a tertiary hospital over a 12-month period. The occurrence of sepsis, organ-related infection, and antibiotic use were recorded on initial PC consult. Survival was calculated from the point of PC consult to the date of death. RESULTS: Of these patients, 16.6% suffered a recent episode of sepsis (with or without an identifiable organ-related infection) and 23.4% had a recent episode of organ related infection without clinically evident sepsis. Among the patients with sepsis, organ-related infection, or both, 89.7% received antibiotics (intravenous, oral, or both). Median survival of septic and nonseptic patients was 15 and 42 days, respectively. Septic patients who responded poorly to treatment (nonresponders) had a median survival of five days vs. 142 days in good responders. This equates with a hazard ratio of 9.74 for death in antibiotic nonresponders (P<0.05). Median survival for patients with an untreated organ related infection (no sepsis) was 27 days compared with 48 days in a similar cohort receiving antibiotic therapy. Among patients on IV antibiotics, nonresponders had a median survival of six days vs. 108 days in responders. For patients on oral antibiotics, nonresponders had a median survival of six days vs. 70 days in responders. CONCLUSION: These findings suggest that a recent episode of sepsis and/or organ-related infection significantly reduces overall patient survival. Favorable antibiotic response is associated with an increase in median survival. These findings suggest that antibiotic treatment may prolong survival, and a time-limited trial may be indicated contingent on goals of care. PMID- 22071168 TI - Elevated levels of Dickkopf-related protein 3 in seminal plasma of prostate cancer patients. AB - BACKGROUND: Expression of Dkk-3, a secreted putative tumor suppressor, is altered in age-related proliferative disorders of the human prostate. We now investigated the suitability of Dkk-3 as a diagnostic biomarker for prostate cancer (PCa) in seminal plasma (SP). METHODS: SP samples were obtained from 81 patients prior to TRUS-guided prostate biopsies on the basis of elevated serum prostate-specific antigen (PSA; > 4 ng/mL) levels and/or abnormal digital rectal examination. A sensitive indirect immunoenzymometric assay for Dkk-3 was developed and characterized in detail. SP Dkk-3 and PSA levels were determined and normalized to total SP protein. The diagnostic accuracies of single markers including serum PSA and multivariate models to discriminate patients with positive (N = 40) and negative (N = 41) biopsy findings were investigated. RESULTS: Biopsy-confirmed PCa showed significantly higher SP Dkk-3 levels (100.9 +/- 12.3 vs. 69.2 +/- 9.4 fmol/mg; p = 0.026). Diagnostic accuracy (AUC) of SP Dkk-3 levels (0.633) was enhanced in multivariate models by including serum PSA (model A; AUC 0.658) or both, serum and SP PSA levels (model B; AUC 0.710). In a subpopulation with clinical follow-up > 3 years post-biopsy to ensure veracity of negative biopsy status (positive biopsy N = 21; negative biopsy N = 25) AUCs for SP Dkk-3, model A and B increased to 0.667, 0.724 and 0.777, respectively. CONCLUSIONS: In multivariate models to detect PCa, inclusion of SP Dkk-3 levels, which were significantly elevated in biopsy-confirmed PCa patients, improved the diagnostic performance compared with serum PSA only. PMID- 22071169 TI - Boosting runtime-performance of photon pencil beam algorithms for radiotherapy treatment planning. AB - Pencil beam algorithms are still considered as standard photon dose calculation methods in Radiotherapy treatment planning for many clinical applications. Despite their established role in radiotherapy planning their performance and clinical applicability has to be continuously adapted to evolving complex treatment techniques such as adaptive radiation therapy (ART). We herewith report on a new highly efficient version of a well-established pencil beam convolution algorithm which relies purely on measured input data. A method was developed that improves raytracing efficiency by exploiting the capability of modern CPU architecture for a runtime reduction. Since most of the current desktop computers provide more than one calculation unit we used symmetric multiprocessing extensively to parallelize the workload and thus decreasing the algorithmic runtime. To maximize the advantage of code parallelization, we present two implementation strategies - one for the dose calculation in inverse planning software, and one for traditional forward planning. As a result, we could achieve on a 16-core personal computer with AMD processors a superlinear speedup factor of approx. 18 for calculating the dose distribution of typical forward IMRT treatment plans. PMID- 22071167 TI - Development of a prognostic model for six-month mortality in older adults with declining health. AB - CONTEXT: Estimation of six-month prognosis is essential in hospice referral decisions, but accurate, evidence-based tools to assist in this task are lacking. OBJECTIVES: To develop a new prognostic model, the Patient-Reported Outcome Mortality Prediction Tool (PROMPT), for six-month mortality in community-dwelling elderly patients. METHODS: We used data from the Medicare Health Outcomes Survey linked to vital status information. Respondents were 65 years old or older, with self-reported declining health over the past year (n=21,870), identified from four Medicare Health Outcomes Survey cohorts (1998-2000, 1999-2001, 2000-2002, and 2001-2003). A logistic regression model was derived to predict six-month mortality, using sociodemographic characteristics, comorbidities, and health related quality of life (HRQOL), ascertained by measures of activities of daily living and the Medical Outcomes Study Short Form-36 Health Survey; k-fold cross validation was used to evaluate model performance, which was compared with existing prognostic tools. RESULTS: The PROMPT incorporated 11 variables, including four HRQOL domains: general health perceptions, activities of daily living, social functioning, and energy/fatigue. The model demonstrated good discrimination (c-statistic=0.75) and calibration. Overall diagnostic accuracy was superior to existing tools. At cut points of 10%-70%, estimated six-month mortality risk sensitivity and specificity ranged from 0.8% to 83.4% and 51.1% to 99.9%, respectively, and positive likelihood ratios at all mortality risk cut points >=40% exceeded 5.0. Corresponding positive and negative predictive values were 23.1%-64.1% and 85.3%-94.5%. Over 50% of patients with estimated six-month mortality risk >=30% died within 12 months. CONCLUSION: The PROMPT, a new prognostic model incorporating HRQOL, demonstrates promising performance and potential value for hospice referral decisions. More work is needed to evaluate the model. PMID- 22071170 TI - UDP-glucuronosyltransferase (UGT) 1A9-overexpressing HeLa cells is an appropriate tool to delineate the kinetic interplay between breast cancer resistance protein (BRCP) and UGT and to rapidly identify the glucuronide substrates of BCRP. AB - The interplay between phase II enzymes and efflux transporters leads to extensive metabolism and low bioavailability for flavonoids. To investigate the simplest interplay between one UDP-glucuronosyltransferase isoform and one efflux transporter in flavonoid disposition, engineered HeLa cells stably overexpressing UGT1A9 were developed, characterized, and further applied to investigate the metabolism of two model flavonoids (genistein and apigenin) and excretion of their glucuronides. The results indicated that the engineered HeLa cells overexpressing UGT1A9 rapidly excreted the glucuronides of genistein and apigenin. The kinetic characteristics of genistein or apigenin glucuronidation were similar with the use of UGT1A9 overexpressed in HeLa cells or the commercially available UGT1A9. Small interfering (siRNA)-mediated UGT1A9 silencing resulted in a substantial decrease in glucuronide excretion (>75%, p < 0.01). Furthermore, a potent inhibitor of breast cancer resistance protein (BCRP), 3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a octahydropyrazino[1',2':1,6]pyrido[3,4-b]indol-3-yl)-propionic acid tert-butyl ester (Ko143), caused, in a dose-dependent manner, a substantial and marked reduction of the clearance (74-94%, p < 0.01), and a substantial increase in the intracellular glucuronide levels (4-8-fold, p < 0.01), resulting in a moderate decrease in glucuronide excretion (19-59%, p < 0.01). In addition, a significant, albeit moderate, reduction in the fraction of genistein metabolized (f(met)) in the presence of Ko143 was observed. In contrast, leukotriene C4 and siRNA against multidrug resistance protein (MRP) 2 and MRP3 did not affect excretion of flavonoid glucuronides. In conclusion, the engineered HeLa cells overexpressing UGT1A9 is an appropriate model to study the kinetic interplay between UGT1A9 and BCRP in the phase II disposition of flavonoids. This simple cell model should also be very useful to rapidly identify whether a phase II metabolite is the substrate of BCRP. PMID- 22071171 TI - Methylation of catechins and procyanidins by rat and human catechol-O methyltransferase: metabolite profiling and molecular modeling studies. AB - Catechins and procyanidins are major polyphenols in plant-derived foods. Despite intensive studies in recent years, neither their biochemical nor their toxicological properties have been clarified sufficiently. This study aimed to compare the methylation of catechins and procyanidins by the enzyme catechol-O methyltransferase (COMT) in vitro. We conducted incubations with rat liver cytosol and human placental cytosol including S-adenosyl-l-methionine. The set of substrates comprised the catechins (-)-epicatechin (EC) and (+)-catechin (CAT), the procyanidin dimers B1, B2, B3, B4, B5, and B7 as well as procyanidin trimer C1. After extraction, metabolites were analyzed by means of liquid chromatography electrospray ionization-mass spectrometry and liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. EC and CAT were converted to two monomethylated metabolites each by human and rat COMT, with the 3'-O-methyl derivatives being consistently the main metabolites. Furthermore, the flavanyl units of procyanidins were methylated consecutively, leading to monomethylated and dimethylated dimeric metabolites as well as monomethylated, dimethylated, and trimethylated C1 metabolites. The methylation status of each flavanyl unit was determined by means of mass spectrometric quinone-methide fragmentation patterns. In addition, molecular modeling studies were performed with the aim to predict the preferred site of methylation and to verify the experimental data. In conclusion, our results indicate that the degree and position of methylation depend clearly on the three-dimensional structure of the entire substrate molecule. PMID- 22071172 TI - Enzymatic characterization and elucidation of the catalytic mechanism of a recombinant bovine glycine N-acyltransferase. AB - Glycine conjugation, a phase II detoxification process, is catalyzed by glycine N acyltransferase (GLYAT; E.C. 2.3.1.13). GLYAT detoxifies various xenobiotics, such as benzoic acid, and endogenous organic acids, such as isovaleric acid, which makes GLYAT important in the management of organic acidemias in humans. We cloned the open reading frame encoding the bovine ortholog of GLYAT from bovine liver mRNA into the bacterial expression vector pColdIII. The recombinant enzyme was expressed, partially purified, and enzymatically characterized. Protein modeling was used to predict Glu226 of bovine GLYAT to be catalytically important. This was assessed by constructing an E226Q mutant and comparing its enzyme kinetics to that of the wild-type recombinant bovine GLYAT. The Michaelis constants for benzoyl-CoA and glycine were determined and were similar for wild type recombinant GLYAT, E226Q recombinant GLYAT, and GLYAT present in bovine liver. At pH 8.0, the E226Q mutant GLYAT had decreased activity, which could be compensated for by increasing the reaction pH. This suggested a catalytic mechanism in which Glu226 functions to deprotonate glycine, facilitating nucleophilic attack on the acyl-CoA. The recombinant bovine GLYAT enzyme, combined with this new understanding of its active site and reaction mechanism, could be a powerful tool to investigate the functional significance of GLYAT sequence variations. Eventually, this should facilitate investigations into the impact of known and novel sequence variations in the human GLYAT gene. PMID- 22071174 TI - Fluidized-bed gasification of dairy manure by Box-Behnken design. AB - Application of excessive animal manure to the land may cause some environmental problems such as eutrophication of surface waters, degradation of ground water quality, and threats to human health. This paper reports an experimental study on the technology of biomass gasification to treat animal waste by analysing the effects of key operating parameters on gasification. In this research, dairy manure from the University of Nebraska dairy farm was first collected and dried, and then gasified in a fluidized-bed, laboratory-scale gasifier to generate syngas. The effects of three parameters, namely temperature, steam to biomass ratio (SBR) and the equivalence ratio (ER), on the gasification were described by a Box-Behnken design (BBD). Results showed that increasing the temperature favoured the formation of all three combustible gases, but the composition of each gas behaved differently according to the changing parameters. The lower heating value of the syngas varied from 2.0 to 4.7 MJ m(-3), indicating gasification could be used as a waste management option to produce bioenergy, and potentially reduce problems associated with the disposal of animal waste. PMID- 22071175 TI - Can hazardous waste become a raw material? The case study of an aluminium residue: a review. AB - The huge number of research studies carried out during recent decades focused on finding an effective solution for the waste treatment, have allowed some of these residues to become new raw materials for many industries. Achieving this ensures a reduction in energy and natural resources consumption, diminishing of the negative environmental impacts and creating secondary and tertiary industries. A good example is provided by the metallurgical industry, in general, and the aluminium industry in this particular case. The aluminium recycling industry is a beneficial activity for the environment, since it recovers resources from primary industry, manufacturing and post-consumer waste. Slag and scrap which were previously considered as waste, are nowadays the raw material for some highly profitable secondary and tertiary industries. The most recent European Directive on waste establishes that if waste is used as a common product and fulfils the existing legislation for this product, then this waste can be defined as 'end-of waste'. The review presented here, attempts to show several proposals for making added-value materials using an aluminium residue which is still considered as a hazardous waste, and accordingly, disposed of in secure storage. The present proposal includes the use of this waste to manufacture glass, glass-ceramic, boehmite and calcium aluminate. Thus the waste might effectively be recovered as a secondary source material for various industries. PMID- 22071176 TI - A field study to estimate the vertical gas diffusivity and permeability of compacted MSW using a barometric pumping analytical model. AB - The measurement of vertical gas diffusivity and permeability of compacted municipal solid waste (MSW) using an analytical gas flow and transport model was evaluated. A series of pressure transducers were buried in a MSW landfill and in situ pressures were modelled using an algorithm that predicts soil-gas pressures based on field-measured barometric pressure data and vertical diffusivity. The vertical gas diffusivity that represented the best-fit of the measured pressures was estimated at 20 locations and ranged from 0.002 to 0.052 m2 s(-1). The vertical gas permeability ranged from 3.3 * 10(-14) to 4.5 * 10(-12) m2 for the upper-most 3 to 6 m of compacted MSW. The shortfalls of applying this method to landfill conditions are also discussed. PMID- 22071177 TI - A review of the current options for the treatment and safe disposal of drill cuttings. AB - Drilling for the exploration and extraction of oil requires the use of drilling fluids which are continuously pumped down and returned carrying the rock phase that is extracted from the well. The potential environmental impacts of contaminated fluids from drilling operations have attracted increasing community awareness and scrutiny. This review article highlights current advances in the treatment of drill cuttings and compares the technologies in terms of cost, time and space requirements. Traditionally, a range of non-biological methods have been employed for the disposal of drill cuttings including burial pits, landfills and re-injection, chemical stabilization and solidification and thermal treatments such as incineration and thermal desorption. More recently, bioremediation has been successfully applied as a treatment process for cuttings. This review provides a current comparison of bioremediation technologies and non biological technologies for the treatment of contaminated drill cuttings providing information on a number of factors that need to be taken into account when choosing the best technology for drilling waste management including the environmental risks associated with disposal of drilling wastes. PMID- 22071178 TI - Estimation of cost reduction and increase for the final disposal associated with the categorization of inert waste landfills in Japan. AB - This study estimates the overall cost savings that have been realized due to disposal of inert wastes in Japan because this material has been deposited in inert waste landfills (IWLs) that are designed exclusively for this purpose, instead of being co-dipsosed with organic wastes in more costly in sanitary landfills (SLs). The total realized cost savings were based on the disposed volume of inert waste and the actual disposal fees for IWLs and SLs for the period 1977-2006. The estimated reduction in expense is 4748 billion JPY for the period. On the other hand, if organic wastes had been deposited in IWLs along with inert wastes, costs would be incurred to clean up the sites because the surrounding environment may be polluted by the decomposition of the non-inert wastes and considerable efforts probably would be required to restore the polluted environment to its normal condition (this is because IWLs typically do not have a barrier system.) The potential cleanup cost was estimated to be 616 to 1226 billion JPY. These estimated costs were compared and it was found that the net reduction in expense was 3522 billion to 4122 billion JPY. Although the expense was reduced substantially, it was noted that a considerable cleanup cost would be generated. In particular, it was found that the increase in cleanup costs becomes most significant after the late 1990s. PMID- 22071179 TI - Invasion of canine erythrocytes by Bartonella vinsonii subsp. berkhoffii. AB - Bartonella vinsonii subsp. berkhoffii is a recognized cause of endocarditis in dogs and human patients and has been associated with cardiac arrhythmias, myocarditis, granulomatous lymphadenitis, polyarthritis, and granulomatous rhinitis in dogs. Little is known regarding the mode of transmission or cellular localization of this bacteria following infection of a canine host. The aim of the current study was to determine whether erythrocytes may serve as a site of infection by B. vinsonii subsp. berkhoffii. In the study, we successfully demonstrate the invasion of canine erythrocytes by a B. vinsonii subsp. berkhoffii genotype III strain using an in vitro model system. Dog erythrocytes were incubated with B. vinsonii subsp. berkhoffii after which tubes were treated with gentamicin at 12, 24, and 48 h post-inoculation. After gentamicin elimination of extracellular bacteria, there was a gradual increase in intra erythrocytic bacteria, as assessed by colony forming units per ml, at each collection time point. The largest recovery of intracellular bacteria occurred at 48 h post-infection. These results suggest that canine erythrocytes may serve in the maintenance of bacteremia due to B. vinsonii subsp. berkhoffii within an infected host. PMID- 22071180 TI - Associative learning between odorants and mechanosensory punishment in larval Drosophila. AB - We tested whether Drosophila larvae can associate odours with a mechanosensory disturbance as a punishment, using substrate vibration conveyed by a loudspeaker (buzz:). One odour (A) was presented with the buzz, while another odour (B) was presented without the buzz (A/B training). Then, animals were offered the choice between A and B. After reciprocal training (A/B), a second experimental group was tested in the same way. We found that larvae show conditioned escape from the previously punished odour. We further report an increase of associative performance scores with the number of punishments, and an increase according to the number of training cycles. Within the range tested (between 50 and 200 Hz), however, the pitch of the buzz does not apparently impact associative success. Last, but not least, we characterized odour-buzz memories with regard to the conditions under which they are behaviourally expressed--or not. In accordance with what has previously been found for associative learning between odours and bad taste (such as high concentration salt or quinine), we report that conditioned escape after odour-buzz learning is disabled if escape is not warranted, i.e. if no punishment to escape from is present during testing. Together with the already established paradigms for the association of odour and bad taste, the present assay offers the prospect of analysing how a relatively simple brain orchestrates memory and behaviour with regard to different kinds of 'bad' events. PMID- 22071181 TI - Changes in cardiac performance during hypoxic exposure in the grass shrimp Palaemonetes pugio. AB - In hearts of higher invertebrates as well as vertebrates, the work performed by the ventricle is a function of both rate and contractility. Decapod crustaceans experience a hypoxia-induced bradycardia that is thought to result in an overall reduction in cardiac work; however, this hypothesis has not yet been tested and is the primary purpose of this study. In the grass shrimp Palaemonetes pugio, cardiac pressure and area data were obtained simultaneously, and in vivo, under normoxic (20.2 kPa O(2)) and hypoxic (6.8 or 2.2 kPa O(2)) conditions and integrated to generate pressure-area (P-A) loops. The area enclosed by the P-A loop provides a measure of stroke work and, when multiplied by the heart rate, provides an estimate of both cardiac work and myocardial O(2) consumption. Changes in intra-cardiac pressure (dp/dt) are correlated to the isovolemic contraction phase and provide an indication of stroke work. At both levels of hypoxic exposure, intra-cardiac pressure, dp/dt, stroke work and cardiac work fell significantly. The significant decrease in intra-cardiac pressure provides the primary mechanism for the decrease in stroke work, and, when coupled with the hypoxia-induced bradycardia, it contributes to an overall fall in cardiac work. Compared with normoxic P-A loops, hypoxic P-A loops (at both levels of hypoxia) become curvilinear, indicating a fall in peripheral resistance (which might account for the reduction in intra-cardiac pressure), which would reduce both stroke work and cardiac work and ultimately would serve to reduce myocardial O(2) consumption. This is the most direct evidence to date indicating that the hypoxia induced bradycardia observed in many decapod crustaceans reduces cardiac work and is therefore energetically favorable during acute exposure to conditions of low oxygen. PMID- 22071182 TI - The effect of work cycle frequency on the potentiation of dynamic force in mouse fast twitch skeletal muscle. AB - The purpose of this study was to test the hypothesis that the potentiation of concentric twitch force during work cycles is dependent upon both the speed and direction of length change. Concentric and eccentric forces were elicited by stimulating muscles during the shortening and lengthening phases, respectively, of work cycles. Work cycle frequency was varied in order to vary the speed of muscle shortening and/or lengthening; all forces were measured as the muscle passed though optimal length (L(o)). Both concentric and eccentric force were assessed before (unpotentiated control) and after (potentiated) the application of a tetanic conditioning protocol known to potentiate twitch force output. The influence of the conditioning protocol on relative concentric force was speed dependent, with forces increased to 1.19+/-0.01, 1.25+/-0.01 and 1.30+/-0.01 of controls at 1.5, 3.3 and 6.9 Hz, respectively (all data N=9-10 with P<0.05). In contrast, the conditioning protocol had only a limited effect on eccentric force at these frequencies (range: 1.06+/-0.01 to 0.96+/-0.03). The effect of the conditioning protocol on concentric work (force * distance) was also speed dependent, being decreased at 1.5 Hz (0.84+/-0.01) and increased at 3.3 and 6.9 Hz (1.05+/-0.01 and 1.39+/-0.01, respectively). In contrast, eccentric work was not increased at any frequency (range: 0.88+/-0.02 to 0.99+/-0.01). Thus, our results reveal a hysteresis-like influence of activity-dependent potentiation such that concentric force and/or work were increased but eccentric force and/or work were not. These outcomes may have implications for skeletal muscle locomotor function in vivo. PMID- 22071183 TI - Neuronal correlates of a preference for leading signals in the synchronizing bushcricket Mecopoda elongata (Orthoptera, Tettigoniidae). AB - Acoustically interacting males of the tropical katydid Mecopoda elongata synchronize their chirps imperfectly, so that one male calls consistently earlier in time than the other. In choice situations, females prefer the leader signal, and it has been suggested that a neuronal mechanism based on directional hearing may be responsible for the asymmetric, stronger representation of the leader signal in receivers. Here, we investigated the potential mechanism in a pair of interneurons (TN1 neuron) of the afferent auditory pathway, known for its contralateral inhibitory input in directional hearing. In this interneuron, conspecific signals are reliably encoded under natural conditions, despite high background noise levels. Unilateral presentations of a conspecific chirp elicited a TN1 response where each suprathreshold syllable in the chirp was reliably copied in a phase-locked fashion. Two identical chirps broadcast with a 180 deg spatial separation resulted in a strong suppression of the response to the follower signal, when the time delay was 20 ms or more. Muting the ear on the leader side fully restored the response to the follower signal compared with unilateral controls. Time-intensity trading experiments, in which the disadvantage of the follower signal was traded against higher sound pressure levels, demonstrated the dominating influence of signal timing on the TN1 response, and this was especially pronounced at higher sound levels of the leader. These results support the hypothesis that the female preference for leader signals in M. elongata is the outcome of a sensory mechanism that originally evolved for directional hearing. PMID- 22071184 TI - Changes in wingstroke kinematics associated with a change in swimming speed in a pteropod mollusk, Clione limacina. AB - In pteropod mollusks, the gastropod foot has evolved into two broad, wing-like structures that are rhythmically waved through the water for propulsion. The flexibility of the wings lends a tremendous range of motion, an advantage that could be exploited when changing locomotory speed. Here, we investigated the kinematic changes that take place during an increase in swimming speed in the pteropod mollusk Clione limacina. Clione demonstrates two distinct swim speeds: a nearly constant slow swimming behavior and a fast swimming behavior used for escape and hunting. The neural control of Clione's swimming is well documented, as are the neuromuscular changes that bring about Clione's fast swimming. This study examined the kinematics of this swimming behavior at the two speeds. High speed filming was used to obtain 3D data from individuals during both slow and fast swimming. Clione's swimming operates at a low Reynolds number, typically under 200. Within a given swimming speed, we found that wing kinematics are highly consistent from wingbeat to wingbeat, but differ between speeds. The transition to fast swimming sees a significant increase in wing velocity and angle of attack, and range of motion increases as the wings bend more during fast swimming. Clione likely uses a combination of drag-based and unsteady mechanisms for force production at both speeds. The neuromuscular control of Clione's speed change points to a two-gaited swimming behavior, and we consider the kinematic evidence for Clione's swim speeds being discrete gaits. PMID- 22071185 TI - Developmental trajectories of gene expression reveal candidates for diapause termination: a key life-history transition in the apple maggot fly Rhagoletis pomonella. AB - The timing of dormancy is a rapidly evolving life-history trait playing a crucial role in the synchronization of seasonal life cycles and adaptation to environmental change. But the physiological mechanisms regulating dormancy in animals remain poorly understood. In insects, dormancy (diapause) is a developmentally dynamic state, and the mechanisms that control diapause transitions affect seasonal timing. Here we used microarrays to examine patterns of gene expression during dormancy termination: a crucial life-history transition in the apple maggot fly Rhagoletis pomonella (Walsh). This species is a model system for host race formation and ecological speciation via changes in diapause regulation of seasonality. Our goal was to pinpoint the timing of the transition from diapause to post-diapause development and to identify candidate genes and pathways for regulation of diapause termination. Samples were taken at six metabolically defined developmental landmarks, and time-series analysis suggests that release from metabolic depression coincides with preparation for or resumption of active cell cycling and morphogenesis, defining the 'end' of diapause. However, marked changes in expression, including members of pathways such as Wnt and TOR signaling, also occur prior to the metabolic rate increase, electing these pathways as candidates for early regulation of diapause termination. We discuss these results with respect to generalities in insect diapause physiology and to our long-term goal of identifying mechanisms of diapause adaptation in the Rhagoletis system. PMID- 22071186 TI - Kingfisher feathers--colouration by pigments, spongy nanostructures and thin films. AB - The colours of the common kingfisher, Alcedo atthis, reside in the barbs of the three main types of feather: the orange breast feathers, the cyan back feathers and the blue tail feathers. Scanning electron microscopy showed that the orange barbs contain small pigment granules. The cyan and blue barbs contain spongy nanostructures with slightly different dimensions, causing different reflectance spectra. Imaging scatterometry showed that the pigmented barbs create a diffuse orange scattering and the spongy barb structures create iridescence. The extent of the angle-dependent light scattering increases with decreasing wavelength. All barbs have a cortical envelope with a thickness of a few micrometres. The reflectance spectra of the cortex of the barbs show oscillations when measured from small areas, but when measured from larger areas the spectra become wavelength independent. This can be directly understood with thin film modelling, assuming a somewhat variable cortex thickness. The cortex reflectance appears to be small but not negligible with respect to the pigmentary and structural barb reflectance. PMID- 22071187 TI - Flea infestation does not cause a long-term increase in energy metabolism in Gerbillus nanus. AB - Fleas can increase the metabolic rate of their hosts. It has been suggested that a constitutive response, in which the host constantly maintains a relatively high level of energy metabolism to combat the parasite, is advantageous for hosts with high parasite infestation, while an induced response, in which the host increases energy metabolism in response to a parasite attack, is advantageous with low parasite infestation. As free-living Gerbillus nanus show a relatively low flea infestation, we hypothesized that this host uses an induced strategy and, consequently, flea infestation would not impose a long-term effect on energy metabolism. In a previous study in spring, higher field metabolic rate (FMR) was found in free-living parasitized than in non-parasitized G. nanus. In this study, G. nanus were captured at Hazeva in spring; some had fleas (N=14) and some did not (N=10). We brought them to the laboratory, removed the fleas from those that were infested and, after 3 weeks, measured average daily metabolic rate (ADMR) of all rodents. ADMR averaged 8.68+/-0.95 kJ g(-0.54) day(-1) for all rodents and was similar between previously parasitized and non-parasitized G. nanus while free living. Thus, the hypothesis that flea infestation does not have a long-term effect on energy metabolism was supported, as was the idea of an induced over a constitutive immune response by G. nanus in combating parasites. PMID- 22071188 TI - Locomotor activity during the frenzy swim: analysing early swimming behaviour in hatchling sea turtles. AB - Swimming effort of hatchling sea turtles varies across species. In this study we analysed how swim thrust is produced in terms of power stroke rate, mean maximum thrust per power stroke and percentage of time spent power stroking throughout the first 18 h of swimming after entering the water, in both loggerhead and flatback turtle hatchlings and compared this with previous data from green turtle hatchlings. Loggerhead and green turtle hatchlings had similar power stroke rates and percentage of time spent power stroking throughout the trial, although mean maximum thrust was always significantly higher in green hatchlings, making them the most vigorous swimmers in our three-species comparison. Flatback hatchlings, however, were different from the other two species, with overall lower values in all three swimming variables. Their swimming effort dropped significantly during the first 2 h and kept decreasing significantly until the end of the trial at 18 h. These results support the hypothesis that ecological factors mould the swimming behaviour of hatchling sea turtles, with predator pressure being important in determining the strategy used to swim offshore. Loggerhead and green turtle hatchlings seem to adopt an intensely vigorous and energetically costly frenzy swim that would quickly take them offshore into the open ocean in order to reduce their exposure to near-shore aquatic predators. Flatback hatchlings, however, are restricted in geographic distribution and remain within the continental shelf region where predator pressure is probably relatively constant. For this reason, flatback hatchlings might use only part of their energy reserves during a less vigorous frenzy phase, with lower overall energy expenditure during the first day compared with loggerhead and green turtle hatchlings. PMID- 22071190 TI - Urotensin II and its receptor in the killifish gill: regulators of NaCl extrusion. AB - The peptide urotensin II (UII) and its receptor (UT) mediate cardiovascular and renal effects in both mammals and fishes. In both groups, vasopressor and diuretic responses predominate, although, in mammals, some secondary vasodilatation is found, mediated by secondary release of nitric oxide or prostacyclin. In fishes, gill extrusion of NaCl is inhibited by UII, but a single study has determined that UT is expressed in gill vasculature, not on the epithelium that mediates the transport. To begin to clarify the pathways involved in UII inhibition of gill transport, we have cloned the cDNA encoding UII and UT from the euryhaline killifish (Fundulus heteroclitus L.) gill and spinal cord, quantified UT mRNA expression in various tissues and measured relative expression in gill tissue from fish acclimated to seawater (SW) vs fresh water (FW). We have also localized UT in the gill epithelium, and measured the effect of UII on ion transport across the opercular epithelium. We found that both UII and UT are synthesized in the gill of F. heteroclitus and that gill UT mRNA levels are ~80% higher in SW- vs FW-acclimated individuals. In addition, UII inhibits NaCl transport across the opercular epithelium in a concentration-dependent manner, and this inhibition is at least partially mediated by both nitric oxide and a prostanoid. PMID- 22071189 TI - IRS and TOR nutrient-signaling pathways act via juvenile hormone to influence honey bee caste fate. AB - Regardless of genetic makeup, a female honey bee becomes a queen or worker depending on the food she receives as a larva. For decades, it has been known that nutrition and juvenile hormone (JH) signaling determine the caste fate of the individual bee. However, it is still largely unclear how these factors are connected. To address this question, we suppressed nutrient sensing by RNA interference (RNAi)-mediated gene knockdown of IRS (insulin receptor substrate) and TOR (target of rapamycin) in larvae reared on queen diet. The treatments affected several layers of organismal organization that could play a role in the response to differential nutrition between castes. These include transcript profiles, proteomic patterns, lipid levels, DNA methylation response and morphological features. Most importantly, gene knockdown abolished a JH peak that signals queen development and resulted in a worker phenotype. Application of JH rescued the queen phenotype in either knockdown, which demonstrates that the larval response to JH remains intact and can drive normal developmental plasticity even when IRS or TOR transcript levels are reduced. We discuss our results in the context of other recent findings on honey bee caste and development and propose that IRS is an alternative substrate for the Egfr (epidermal growth factor receptor) in honey bees. Overall, our study describes how the interplay of nutritional and hormonal signals affects many levels of organismal organization to build different phenotypes from identical genotypes. PMID- 22071191 TI - Pharmacological characterisation of apical Na+ and Cl- transport mechanisms of the anal papillae in the larval mosquito Aedes aegypti. AB - The anal papillae of freshwater mosquito larvae are important sites of NaCl uptake, thereby acting to offset the dilution of the hemolymph by the dilute habitat. The ion-transport mechanisms in the anal papillae are not well understood. In this study, the scanning ion-selective electrode technique (SIET) was utilized to measure ion fluxes at the anal papillae, and pharmacological inhibitors of ion transport were utilized to identify ion-transport mechanisms. Na(+) uptake by the anal papillae was inhibited by bafilomycin and phenamil but not by HMA. Cl(-) uptake was inhibited by methazolamide, SITS and DIDS but not by bafilomycin. H(+) secretion was inhibited by bafilomycin and methazolamide. Ouabain and bumetanide had no effect on NaCl uptake or H(+) secretion. Together, the results suggest that Na(+) uptake at the apical membrane occurs through a Na(+) channel that is driven by a V-type H(+)-ATPase and that Cl(-) uptake occurs through a Cl(-)/HCO(3)(-) exchanger, with carbonic anhydrase providing H(+) and HCO(3)(-) to the V-type H(+)-ATPase and exchanger, respectively. PMID- 22071192 TI - Rapid contrast gain reduction following motion adaptation. AB - Neural and sensory systems adapt to prolonged stimulation to allow signaling across broader input ranges than otherwise possible with the limited bandwidth of single neurons and receptors. In the visual system, adaptation takes place at every stage of processing, from the photoreceptors that adapt to prevailing luminance conditions, to higher-order motion-sensitive neurons that adapt to prolonged exposure to motion. Recent experiments using dynamic, fluctuating visual stimuli indicate that adaptation operates on a time scale similar to that of the response itself. Further work from our own laboratory has highlighted the role for rapid motion adaptation in reliable encoding of natural image motion. Physiologically, motion adaptation can be broken down into four separate components. It is not clear from the previous studies which of these motion adaptation components are involved in the fast and dynamic response changes. To investigate the adapted response in more detail, we therefore analyzed the effect of motion adaptation using a test-adapt-test protocol with adapting durations ranging from 20 ms to 20 s. Our results underscore the very rapid rate of motion adaptation, suggesting that under free flight, visual motion-sensitive neurons continuously adapt to the changing scenery. This might help explain recent observations of strong invariance in the response to natural scenes with highly variable contrast and image structure. PMID- 22071193 TI - Energy expenditure of freely swimming adult green turtles (Chelonia mydas) and its link with body acceleration. AB - Marine turtles are globally threatened. Crucial for the conservation of these large ectotherms is a detailed knowledge of their energy relationships, especially their at-sea metabolic rates, which will ultimately define population structure and size. Measuring metabolic rates in free-ranging aquatic animals, however, remains a challenge. Hence, it is not surprising that for most marine turtle species we know little about the energetic requirements of adults at sea. Recently, accelerometry has emerged as a promising tool for estimating activity specific metabolic rates of animals in the field. Accelerometry allows quantification of the movement of animals (ODBA/PDBA, overall/partial dynamic body acceleration), which, after calibration, might serve as a proxy for metabolic rate. We measured oxygen consumption rates (V(O(2))) of adult green turtles (Chelonia mydas; 142.1+/-26.9 kg) at rest and when swimming within a 13 m long swim channel, using flow-through respirometry. We investigated the effect of water temperature (T(w)) on turtle and tested the hypothesis that turtle body acceleration can be used as a proxy for V(O(2)). Mean mass-specific V(O(2)) (sV(O(2))) of six turtles when resting at a T(w) of 25.8+/-1.0 degrees C was 0.50+/-0.09 ml min(-1) kg(-0.83). sV(O(2))increased significantly with T(w) and activity level. Changes in sV(O(2)) were paralleled by changes in respiratory frequency (f(R)). Deploying bi-axial accelerometers in conjunction with respirometry, we found a significant positive relationship between sV(O(2)) and PDBA that was modified by T(w). The resulting predictive equation was highly significant (r(2)=0.83, P<0.0001) and associated error estimates were small (mean algebraic error 3.3%), indicating that body acceleration is a good predictor of V(O(2)) in green turtles. Our results suggest that accelerometry is a suitable method to investigate marine turtle energetics at sea. PMID- 22071194 TI - Divergent transcriptomic responses to repeated and single cold exposures in Drosophila melanogaster. AB - Insects in the field are exposed to multiple bouts of cold, and there is increasing evidence that the fitness consequences of repeated cold exposure differ from the impacts of a single cold exposure. We tested the hypothesis that different kinds of cold exposure (in this case, single short, prolonged and repeated cold exposure) would result in differential gene expression. We exposed 3 day old adult female wild-type Drosophila melanogaster (Diptera: Drosophilidae) to -0.5 degrees C for a single 2 h exposure, a single 10 h exposure, or five 2 h exposures on consecutive days, and extracted RNA after 6 h of recovery. Global gene expression was quantified using an oligonucleotide microarray and validated with real-time PCR using different biological replicates. We identified 76 genes upregulated in response to multiple cold exposure, 69 in response to prolonged cold exposure and 20 genes upregulated in response to a single short cold exposure, with a small amount of overlap between treatments. Three genes- Turandot A, Hephaestus and CG11374--were upregulated in response to all three cold exposure treatments. Key functional groups upregulated include genes associated with muscle structure and function, the immune response, stress response, carbohydrate metabolism and egg production. We conclude that cold exposure has wide-ranging effects on gene expression in D. melanogaster and that increased duration or frequency of cold exposure has impacts different to those of a single short cold exposure. This has important implications for extrapolating laboratory studies of insect overwintering that are based on only a single cold exposure. PMID- 22071196 TI - Black wildebeest skeletal muscle exhibits high oxidative capacity and a high proportion of type IIx fibres. AB - The aim of the study was to investigate the skeletal muscle characteristics of black wildebeest (Connochaetes gnou) in terms of fibre type and metabolism. Samples were obtained post mortem from the vastus lateralis and longissimus lumborum muscles and analysed for myosin heavy chain (MHC) content. Citrate synthase (CS), 3-hydroxyacyl co A dehydrogenase (3HAD), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and creatine kinase (CK) activities were measured spectrophotometrically to represent the major metabolic pathways in these muscles. Both muscles had less than 20% MHC I, whereas MHC IIa and MHC IIx were expressed in excess of 50% in the vastus lateralis and longissimus lumborum muscles, respectively. Overall fibre size was 2675+/-1034 MUm(2), which is small compared with other species. Oxidative capacity (CS and 3HAD) in both muscles was high and did not differ from one another, but the longissimus lumborum had significantly (P<0.05) higher PFK, LDH and CK activities. No relationships were observed between fibre type and the oxidative and oxygen-independent metabolic capacity as measured by specific enzyme activities. This study confirms the presence of both fast-twitch fibres and high oxidative capacity in black wildebeest, indicating an animal that can run very fast but is also fatigue resistant. PMID- 22071195 TI - Hydrogen sulfide (H2S) and hypoxia inhibit salmonid gastrointestinal motility: evidence for H2S as an oxygen sensor. AB - Hydrogen sulfide (H(2)S) has been shown to affect gastrointestinal (GI) motility and signaling in mammals and O(2)-dependent H(2)S metabolism has been proposed to serve as an O(2) 'sensor' that couples hypoxic stimuli to effector responses in a variety of other O(2)-sensing tissues. The low P(O2) values and high H(2)S concentrations routinely encountered in the GI tract suggest that H(2)S might also be involved in hypoxic responses in these tissues. In the present study we examined the effect of H(2)S on stomach, esophagus, gallbladder and intestinal motility in the rainbow trout (Oncorhynchus mykiss) and coho salmon (Oncorhynchus kisutch) and we evaluated the potential for H(2)S in oxygen sensing by examining GI responses to hypoxia in the presence of known inhibitors of H(2)S biosynthesis and by adding the sulfide donor cysteine (Cys). We also measured H(2)S production by intestinal tissue in real time and in the presence and absence of oxygen. In tissues exhibiting spontaneous contractions, H(2)S inhibited contraction magnitude (area under the curve and amplitude) and frequency, and in all tissues it reduced baseline tension in a concentration-dependent relationship. Longitudinal intestinal smooth muscle was significantly more sensitive to H(2)S than other tissues, exhibiting significant inhibitory responses at 1-10 MUmol l( 1) H(2)S. The effects of hypoxia were essentially identical to those of H(2)S in longitudinal and circular intestinal smooth muscle; of special note was a unique transient stimulatory effect upon application of both hypoxia and H(2)S. Inhibitors of enzymes implicated in H(2)S biosynthesis (cystathionine beta synthase and cystathionine gamma-lyase) partially inhibited the effects of hypoxia whereas the hypoxic effects were augmented by the sulfide donor Cys. Furthermore, tissue production of H(2)S was inversely related to O(2); addition of Cys to intestinal tissue homogenate stimulated H(2)S production when the tissue was gassed with 100% nitrogen (~0% O(2)), whereas addition of oxygen (~10% O(2)) reversed this to net H(2)S consumption. This study shows that the inhibitory effects of H(2)S on the GI tract of a non-mammalian vertebrate are identical to those reported in mammals and they provide further evidence that H(2)S is a key mediator of the hypoxic response in a variety of O(2)-sensitive tissues. PMID- 22071197 TI - The inotropic effects of ammonia on isolated perfused rat hearts and the mechanisms involved. AB - Ammonia (NH(3)) is a common exogenous gas in the atmosphere, as well as an endogenous chemical produced by amino acid catabolism and other pathways in vivo. Physiological and pathophysiological roles of NH(3) in the nervous system have been studied. Recently, endogenous NH(3) has been suggested to be a gas transmitter. However, so far the role of NH(3) in cardiovascular functions has not been reported. The present study was designed to investigate the inotropic effects of NH(3) on isolated perfused rat hearts and the possible mechanisms involved in these effects. The results showed that NH(3) had a positive inotropic effect in a concentration-dependent manner and produced a higher positive effect than NaOH and NH(4)Cl. At low concentrations, the effect of NH(3) on cardiac function was caused by NH(3) molecules; at high concentrations, the effect of NH(3) on hearts may be partly correlated with a change of pH value, but was mainly caused by NH(3) molecules. The mechanisms involved in the NH(3)-induced positive inotropic effect may be related to the ATP-sensitive K(+) (K(ATP)) channel and the nitric oxide (NO)-cyclic GMP (cGMP) signaling pathway. In addition, at a concentration of 1.5 mmol l(-1), NH(3) significantly increased the activity of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary perfusate and decreased the activity of Na(+),K(+)-ATPase and Ca(2+),Mg(2+) ATPase in the hearts. These results indicate that NH(3) at physiological or low concentrations may play a modulatory role in heart function, but at high concentrations had a damaging effect on isolated rat hearts. PMID- 22071198 TI - The recruiter's excitement--features of thoracic vibrations during the honey bee's waggle dance related to food source profitability. AB - The honey bee's waggle dance constitutes a remarkable example of an efficient code allowing social exploitation of available feeding sites. In addition to indicating the position (distance, direction) of a food patch, both the occurrence and frequency of the dances depend on the profitability of the exploited resource (sugar concentration, solution flow rate). During the waggle dance, successful foragers generate pulsed thoracic vibrations that putatively serve as a source of different kinds of information for hive bees, who cannot visually decode dances in the darkness of the hive. In the present study, we asked whether these vibrations are a reliable estimator of the excitement of the dancer when food profitability changes in terms of both sugar concentration and solution flow rate. The probability of producing thoracic vibrations as well as several features related to their intensity during the waggle phase (pulse duration, velocity amplitude, duty cycle) increased with both these profitability variables. The number of vibratory pulses, however, was independent of sugar concentration and reward rate exploited. Thus, pulse number could indeed be used by dance followers as reliable information about food source distance, as suggested in previous studies. The variability of the dancer's thoracic vibrations in relation to changes in food profitability suggests their role as an indicator of the recruiter's motivational state. Hence, the vibrations could make an important contribution to forager reactivation and, consequently, to the organisation of collective foraging processes in honey bees. PMID- 22071199 TI - [Randomised controlled trial: the role of diet and exercise in women with metabolic syndrome]. AB - OBJECTIVE: To evaluate a program of nutritional recommendations and exercise in women with metabolic syndrome. DESIGN: Multicentre randomised controlled trial. LOCATION: Primary Health Care, Holguin, Cuba. PARTICIPANTS: A cluster sample of 150 obese women with metabolic syndrome without glucose disturbances, were randomly assigned to a control (n=70) or experimental (n=80) group. A total of 62 women in the control group and 60 in the intervention group completed the study (June 2008-July 2009). INTERVENTIONS: Low calorie diets and a program of exercises in the experimental group. Usual care in the control group. MEASUREMENTS: Body weight, body mass index, waist circumference, blood pressure, blood glucose and lipid profile. RESULTS: Compared to the control group, after one year, the experimental group had a lower, diastolic blood pressure (78+/-0.9 vs 91+/-1.1mm Hg), total cholesterol (4.7+/-0.1 vs 6.0 +/-0.1mmol/L), triglycerides (1.9+/-0.0 vs 2.9+/-0.1mmol/L) and LDL cholesterol (2.5+/-0.0 vs 3.5+/-0.1mmol/L), and a higher HDL-cholesterol (1.2+/-0.0 vs 1.1+/-0.0mmol/L). There were no appreciable changes in weight, body mass index, waist circumference, systolic blood pressure and blood glucose. CONCLUSIONS: We demonstrated the effectiveness of the intervention program on blood pressure and blood lipid profile. PMID- 22071200 TI - Percutaneous closure of an aortic prosthetic paravalvar leak: an Australian first. AB - Percutaneous intervention is becoming an increasingly recognised modality for the management of prosthetic paravalvar leaks (PVLs) with particular utility in severely symptomatic non-surgical candidates. To date, application of this intervention has predominantly involved closure of mitral valve PVLs. Consequently, current literature on its application to aortic PVLs is limited. This article describes what we believe to be the first percutaneous closure of an aortic prosthetic PVL in Australia. PMID- 22071202 TI - Idiopathic hypertrophic pachymeningitis mimicking neurosarcoidosis. PMID- 22071201 TI - Right minithoracotomy versus full sternotomy for the aortic valve replacement: preliminary results. AB - BACKGROUND: Minimally invasive surgery (MIS) for aortic valve replacement (AVR) is going to increase with different techniques described so far. We hereby report the results of AVR through a right minithoracotomy (RM) compared to a median sternotomy (MS). MATERIALS AND METHODS: One hundred patients operated for isolated AVR by the same surgeon (chief of the department) were enrolled and allocated to: MS (group A, 50 patients, 26 females, mean age 69.9 +/- 12.4 years). RM (group B, 50 patients, 27 females, mean age 71.6 +/- 11.2 years). Mean logistic Euroscores were, respectively, 6.5 +/- 4.0 and 8.0 +/- 5.9 (p=ns). RESULTS: Mean duration of cardiopulmonary by-pass (CPB) was 62.8 +/- 18.3 min in group A and 101.4 +/- 35.2 min in group B (p<0.05); cross-clamp was 44.8 +/- 13.4 min in group A and 74.6 +/- 26.7 min in group B (p<0.05). Thirty-day mortality was 2 (4%) in group A and 0 in group B (p=ns). ICU stay and hospital stay did not significantly differ amongst two groups. The incidence of bleeding was lower in group B, showing a slight reduction of blood transfusions and re-explorations (p=ns). CONCLUSIONS: Our experience shows that RM offers a good 30-day survival and a lower incidence of mediastinitis or osteomyelitis. The risk of insufficient vision or sudden complications is safely managed by enlarging the surgical incision through a transverse sternotomy. PMID- 22071203 TI - Atypical central neurocytoma of fourth ventricle with hemorrhagic complication during surgery in a child. PMID- 22071204 TI - Pseudo-Foster Kennedy syndrome in a young woman with meningioma infiltrating the superior sagittal sinus. PMID- 22071205 TI - Patients with psychogenic non-epileptic seizures referred to a tertiary epilepsy centre: patient characteristics in relation to diagnostic delay. AB - OBJECTIVE: This clinical study examines patient and seizure characteristics of patients with psychogenic non-epileptic seizures (PNES) in a tertiary epilepsy centre. The main focus was whether a new subgroup of PNES patients emerged with a relatively short referral time and possible specific characteristics. METHODS: All PNES patients referred to a specialist program in our centre between mid 2007 and mid 2009 were consecutively included. This yielded a study cohort of 90 patients. RESULTS: The majority of the patients have a patient history with many medical symptoms and they were or had been in treatment by a medical specialist. Furthermore diffuse psychological/psychiatric symptoms and subsequent treatments are also remarkably common, in general without a clear psychological diagnosis. The average time between seizure onset and referral to an epilepsy centre is remarkably low (4.29 years). About 50% of the patients were referred within 2 years of seizure onset. This 'active high speed referral group' had significantly more previous psychological complaints, significantly more previous psychological/psychiatric treatments and a trend towards more previous medical investigations. CONCLUSION: There seems to be a new subgroup of PNES patients with a short referral time, characterized by a more active attitude towards examination of the symptoms in combination with an active attitude to apply for treatment. However, the PNES cohort as a whole is characterized by having somatoform symptoms based on a process of somatization. PMID- 22071206 TI - Spindle cell oncocytoma of the adenohypophysis: report of a rare case and review of literature. PMID- 22071207 TI - Severity of community-acquired pneumonia treated with low-dose adjunctive corticosteroid. PMID- 22071209 TI - Association of catalytic iron with cardiovascular disease. AB - The ability of iron to cycle reversibly between its ferrous and ferric oxidation states is essential for the biological functions of iron but may contribute to vascular injury through the generation of powerful oxidant species. We examined the association between chemical forms of iron that can participate in redox cycling, often referred to as "catalytic" or "labile" iron, and cardiovascular disease (CVD). In our cross-sectional study of 496 participants, 85 had CVD. Serum catalytic iron was measured using the bleomycin-detectable iron assay that detects biologically active iron. The odds of existing CVD for subjects in the upper third of catalytic iron were 10 times that of subjects with lower catalytic iron in unadjusted analyses. The association was decreased by 1/2 by age adjustment, but little additional attenuation occurred after adjusting for age, Framingham Risk Score, estimated glomerular filtration rate, hypertension status, high-density lipoprotein cholesterol, and systolic blood pressure, with the association remaining strong and significant (odds ratio 3.8, 95% confidence interval 1.4 to 10.1). In conclusion, we provide preliminary evidence for a strong detrimental association between high serum catalytic iron and CVD even after adjusting for several co-morbid conditions; however, broader prospective studies are needed to confirm these findings, which would support therapeutic trials to assess the beneficial effects of iron chelators on CVD. PMID- 22071208 TI - Association of frontal QRS-T angle--age risk score on admission electrocardiogram with mortality in patients admitted with an acute coronary syndrome. AB - Risk assessment is central to the management of acute coronary syndromes. Often, however, assessment is not complete until the troponin concentration is available. Using 2 multicenter prospective observational studies (Evaluation of Methods and Management of Acute Coronary Events [EMMACE] 2, test cohort, 1,843 patients; and EMMACE-1, validation cohort, 550 patients) of unselected patients with acute coronary syndromes, a point-of-admission risk stratification tool using frontal QRS-T angle derived from automated measurements and age for the prediction of 30-day and 2-year mortality was evaluated. Two-year mortality was lowest in patients with frontal QRS-T angles <38 degrees and highest in patients with frontal QRS-T angles >104 degrees (44.7% vs 14.8%, p <0.001). Increasing frontal QRS-T angle-age risk (FAAR) scores were associated with increasing 30-day and 2-year mortality (for 2-year mortality, score 0 = 3.7%, score 4 = 57%; p <0.001). The FAAR score was a good discriminator of mortality (C statistics 0.74 [95% confidence interval 0.71 to 0.78] at 30 days and 0.77 [95% confidence interval 0.75 to 0.79] at 2 years), maintained its performance in the EMMACE-1 cohort at 30 days (C statistics 0.76 (95% confidence interval 0.71 to 0.8] at 30 days and 0.79 (95% confidence interval 0.75 to 0.83] at 2 years), in men and women, in ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction, and compared favorably with the Global Registry of Acute Coronary Events (GRACE) score. The integrated discrimination improvement (age to FAAR score at 30 days and at 2 years in EMMACE-1 and EMMACE-2) was p <0.001. In conclusion, the FAAR score is a point-of-admission risk tool that predicts 30-day and 2-year mortality from 2 variables across a spectrum of patients with acute coronary syndromes. It does not require the results of biomarker assays or rely on the subjective interpretation of electrocardiograms. PMID- 22071210 TI - Impact of plaque burden in the left main coronary artery determined by intravascular ultrasound on cardiovascular events in a Japanese population undergoing percutaneous coronary intervention. AB - The left main coronary artery (LMCA) is a particularly important target of atherosclerotic plaque accumulation. The aim of this study was to investigate the connection between subclinical plaque burden in the LMCA measured by intravascular ultrasound and future cardiovascular events. Two hundred eighteen consecutive patients underwent percutaneous coronary intervention for the left anterior descending coronary artery or the left circumflex coronary artery under intravascular ultrasound guidance. Plaque burden in the LMCA was analyzed for these patients, and major adverse cardiac events were also evaluated. Data were analyzed by grouping the patients into tertiles according to plaque burden values; tertile 1, <32% area stenosis; tertile 2, 32% to 45% area stenosis; and tertile 3, >45% area stenosis. During a 3-year follow-up period (average 16.1 months), 12% of tertile 1, 18% of tertile 2, and 40% of tertile 3 experienced major adverse cardiac events, mostly due to repeat revascularization (p <0.001). On Cox multivariate analysis, plaque burden in the LMCA (per percentage) detected by intravascular ultrasound remained an independent significant predictor of major adverse cardiac events (hazard ratio 1.04, 95% confidence interval 1.02 to 1.07) and future revascularization (hazard ratio 1.05, 95% confidence interval 1.02 to 1.07) (p <0.001). In conclusion, plaque burden in the LMCA is useful as an indicator of coronary atherosclerosis and may be a significant predictor of cardiovascular events, especially revascularization. PMID- 22071211 TI - Familial restrictive cardiomyopathy with 12 affected family members. PMID- 22071212 TI - Vitamin D deficiency and supplementation and relation to cardiovascular health. AB - Recent evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. The effect of vitamin D supplementation, however, has not been well studied. We examined the associations between vitamin D deficiency, vitamin D supplementation, and patient outcomes in a large cohort. Serum vitamin D measurements for 5 years and 8 months from a large academic institution were matched to patient demographic, physiologic, and disease variables. The vitamin D levels were analyzed as a continuous variable and as normal (>=30 ng/ml) or deficient (<30 ng/ml). Descriptive statistics, univariate analysis, multivariate analysis, survival analysis, and Cox proportional hazard modeling were performed. Of 10,899 patients, the mean age was 58 +/- 15 years, 71% were women (n = 7,758), and the average body mass index was 30 +/- 8 kg/m(2). The mean serum vitamin D level was 24.1 +/- 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) were in the normal vitamin D range and 7,665 (70.3%) were deficient. Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency. PMID- 22071213 TI - Comparison of patients with pulmonary arterial hypertension with versus without right-sided mechanical alternans. AB - The clinical implications of mechanical alternans in patients with pulmonary arterial hypertension (PAH) remain unknown. In this study, the prevalence, characteristics, and prognostic implications of mechanical alternans in patients with PAH were investigated. Thirty-two consecutive patients with PAH confirmed by cardiac catheterization from 2000 to 2010 were included in this cohort study. During cardiac catheterization, 8 patients (25%) showed mechanical alternans at rest. All alternans were detected in the right ventricle and pulmonary trunk. Serum level of brain natriuretic peptide (584 +/- 177 vs 238 +/- 252 pg/ml, p = 0.001), World Health Organization functional class (3.5 +/- 0.5 vs 2.9 +/- 0.4, p = 0.02), mean pulmonary arterial pressure (59 +/- 10 vs 47 +/- 18 mm Hg, p = 0.03), mean right atrial pressure (10 +/- 4 vs 5 +/- 4 mm Hg, p = 0.01), right ventricular end-diastolic pressure (15 +/- 5 vs 9 +/- 5 mm Hg, p = 0.01), and heart rate at catheterization (96 +/- 17 vs 70 +/- 11 beats/min, p = 0.003) were significantly higher in patients with alternans than in those without. Twelve month mortality of patients with alternans was higher than in patients without alternans (p = 0.03): the 12-month survival rate after cardiac catheterization was 37% for the alternans group and 75% for the group without alternans. In conclusion, isolated right-sided mechanical alternans is not an uncommon event in patients with PAH. The existence of alternans is associated with the severity of PAH and right ventricular dysfunction and implies a poor prognosis in the short term. PMID- 22071214 TI - Disruption of atherosclerotic neointima as a cause of very late stent thrombosis after bare metal stent implantation. AB - A male who were implanted bare metal stent 11 years ago were admitted for acute coronay syndrome. Optical coherence tomography showed a neointimal disruption and integrated backscatter intravascular ultrasound revealed a lipid pool around the disrupted neointima, suggesting newly formed atherosclerotic neointima developed after bare metal stent implantation. The disruption of atherosclerotic neointima may represent a new potential mechanism of very late stent thrombosis after bare metal stent implantation. PMID- 22071215 TI - Inflammatory and growth factor response to continuous and intermittent exercise in youth with cystic fibrosis. AB - BACKGROUND: Children with cystic fibrosis (CF) tend to suffer from chronic systemic inflammation and may have impaired growth associated with muscle catabolism. Therefore, investigating which type of exercise can elicit an anabolic response with minimal inflammation is of clinical value. METHODS: Twelve children with CF (mean+/-SD; age: 14.7+/-2.3 years, predicted FEV(1): 90.0+/ 21.6%) and biological age-matched controls (age: 13.9+/-2.1 years) completed moderate-intensity, continuous exercise (MICE) and high-intensity, intermittent exercise (HIIE) on separate days. During each exercise, blood was drawn at various time points and analyzed for immune cells, inflammatory cytokines, and growth mediators. RESULTS: At rest, children with CF had higher concentrations of neutrophils and IL-6 compared with controls. In children with CF, HIIE did not affect immune cell subsets or cytokines: TNF-alpha, IL-6, and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). All immune cell subsets and IL-6 increased significantly with MICE in both groups. Growth hormone (GH) increased with both types of exercise, with a greater change from rest during MICE. CONCLUSIONS: HIIE was a sufficient stimulus to increase GH in children with CF, without affecting systemic inflammation. PMID- 22071216 TI - Type VI collagen deficiency induces osteopenia with distortion of osteoblastic cell morphology. AB - Bone consists of type I collagen as a major protein with minor various matrix proteins. Type VI collagen is one of bone matrix proteins but its function is not known. We therefore examined the effects of type VI collagen deficiency on bone. 3D-MUCT analysis revealed that type VI collagen deficiency reduced cancellous bone mass. Cortical bone mass was not affected. Type VI collagen deficiency distorted the shape of osteoblasts both in the cancellous bone and in the cambium layer of periosteal region. Furthermore, type VI collagen deficiency disorganized collagen arrangement. These data indicate that type VI collagen contributes to maintain bone mass. PMID- 22071217 TI - Organochlorine pesticides and polychlorinated biphenyls in sediments and fish from freshwater cultured fish ponds in different agricultural contexts in north eastern France. AB - Organochlorine pesticides (HCB, HCH with alpha-, beta-, and gamma isomers, heptachlor, cis-heptachlor epoxyde, trans-heptachlor epoxyde, endosulfan with alpha- and beta isomers, sulfate endosulfan, o,p'-DDT, p,p'-DDT, o,p'-DDE, p,p' DDE, o,p'-DDD, p,p'-DDD, chlorothalonil, alachlor, aldrin, dieldrin, methoxychlor, oxychlordane, chlordane with alpha- and gamma isomers, p,p'-dicofol and o,p'-dicofol) and indicators PCBs (IUPAC nos. 28, 52, 101, 118, 138, 153, and 180) were studied both in sediments and muscles of farmed fish species (Cyprinus carpio and Perca fluviatilis). Samples were collected from fish ponds located in the hydrographic basin of the Moselle River (Lorraine Region, France). OCPs and PCBs were present at low concentrations both in sediments and fish muscles. Concerning sediments, ?DDTs revealed concentrations ranging from 0.2 to 2.30 ng g(-1) dw and ?PCBs ranged from 0.3 to 3.5 ng g(-1) dw. Concerning fish muscles, the highest concentrations in OCPs were those of p,p'-DDE, with average concentrations of 0.57+/-0.44 ng g(-1) ww for carp and 0.58+/-0.29 ng g(-1) ww for perch. The contamination profiles proved to be different depending on the fish species. Indeed, HCH-isomers, HCB, and dieldrin were detected only for the carp and always at low concentrations. For example, the highest concentration of HCHs was observed for beta-HCH with a mean value of 0.64+/-0.15 ng g(-1) ww for carp. As for PCBs, the levels of ?PCBs ranged from 0.3 to 6.4 ng g(-1) ww in carp muscles and from 0.90 to 5.60 ng g(-1) ww in perch muscles. PMID- 22071218 TI - Identification of sperm subpopulations with defined motility characteristics in ejaculates from Ile de France rams. AB - The aims of this study were to identify different motile sperm subpopulations in fresh ejaculates from six Ile de France rams, by using a computer-assisted sperm motility analysis (CASA) system, and to evaluate the effects of individual ram and season on population distribution. Overall sperm motility and individual kinematic parameters of motile spermatozoa were evaluated for 125,312 spermatozoa, defined by curvilinear velocity (VCL), linear velocity (VSL), average path velocity (VAP), linearity coefficient (LIN), straightness coefficient (STR), wobble coefficient (WOB), mean amplitude of lateral head displacement (ALH) and frequency of head displacement (BCF). A multivariate cluster analysis was carried out to classify these spermatozoa into a reduced number of subpopulations according to their movement patterns. The statistical analysis clustered the whole motile sperm population into five separate groups: subpopulation 1, constituted by rapid, progressive and non sinuous spermatozoa (VCL=126.41 MUm/s, STR=92.87% and LIN=86.47%); subpopulation 2, characterized by progressive spermatozoa with moderate velocity (VCL=74.74 MUm/s and STR=84.03%); subpopulation 3, represented by rapid, progressive and sinuous spermatozoa (VCL=130.45 MUm/s, STR=76.02% and LIN=47.68%); subpopulation 4 represents rapid nonprogressive spermatozoa (VCL=128.69 MUm/s and STR=44.09%); subpopulation 5 includes poorly motile, nonprogressive spermatozoa with a very irregular trajectory (VCL=36.81 MUm/s and STR=47.04%). Our results show the existence of five subpopulations of motile spermatozoa in ram ejaculates. The frequency distribution of spermatozoa within subpopulations was quite similar for the six rams, and the five subpopulations turned out to be very stable along seasons. PMID- 22071219 TI - Phosphate content of beverages in addition to food phosphate additives: real and insidious danger for renal patients. PMID- 22071220 TI - Gastrointestinal symptoms and nutritional status in women and men on maintenance hemodialysis. AB - OBJECTIVE: The main objective was to investigate whether the prevalences of nausea, vomiting, diarrhea, and reduced appetite varied by gender in maintenance hemodialysis (MHD) patients. We also evaluated whether these symptoms explain female-male difference in nutritional status. DESIGN: Cross section of baseline data of the Prospective Study of the Prognosis in Chronic Hemodialysis Patients. SETTING: Dialysis units in the city of Salvador, Brazil. PATIENTS: Three hundred ninety-seven men and 287 women with more than three months on MHD. PREDICTOR VARIABLE: Gender. OUTCOME MEASURES: The patient's self-reported nausea, vomiting, diarrhea, and reduced appetite. The malnutrition-inflammation score (MIS) was used to assess nutritional status. RESULTS: The prevalence of symptoms was 24.3% for reduced appetite, 19.7% for nausea, 12.3% for vomiting, and 3.5% for diarrhea. In a logistic regression model with adjustments for age, diabetes, congestive heart failure, hemoglobin, albumin, Kt/V, and years on dialysis, women were found to have significantly higher odds of reduced appetite (odds ratio [OR] = 1.97), nausea (OR = 1.90), and vomiting (OR = 2.21). MIS was 5.41 +/- 3.18 for women and 4.66 +/- 3.28 for men (P = .002) corresponding to a percentage difference of 13.86%. The female-male difference reduced by more than half after excluding the gastrointestinal symptoms component and by approximately 65% after excluding both the gastrointestinal symptoms and the dietary intake components from the MIS. CONCLUSIONS: The results suggest that the prevalences of nausea, vomiting, and reduced appetite are higher in women than in men on MHD. These gastrointestinal symptoms and perhaps their detrimental effects on dietary intake may partially explain a poorer nutritional status in MHD women. PMID- 22071221 TI - Do patients with pN0 gastric cancer benefit from prophylactic extended lymphadenectomy? AB - PURPOSE: To investigate the impact of prophylactic extended lymphadenectomy on survival for patients with node-negative (pN0) advanced gastric cancer according to the extent of lymph node dissection. METHODS: This study retrospectively investigated the clinicopathological characteristics and prognostic outcomes of 458 patients who had pN0 advanced gastric cancer between 1995 and 2001. Postoperative survival was compared in patients who underwent different extents of prophylactic lymphadenectomy. RESULTS: The overall 5-year and 10-year survival rates were 62.01% (284/458) and 40.83% (187/458), respectively. The survival rates differed significantly in patients who underwent a different extent of prophylactic lymphadenectomy (<=D1+ versus D2 versus D3 versus >=D3) (X(2) = 8.59, P = 0.035). Survival in patients who received less than D1+ dissection, however, were not significantly better than patients who received D2 dissection (X(2) = 0.907, P = 0.341). Survival in patients who received D2 dissection was significantly better than survival in patients who received D3 dissection (X(2) = 5.685, P = 0.017). No differences in postoperative survival rates were observed between patients who received D3 dissection and those received more than D3 dissection (X(2) = 2.468, P = 0.116). Patients who were older than 60 years and receive more than D2 dissection experienced significantly worse postoperative survival than those who received less than D2 dissection (X(2) = 14.885, P = 0.001). The extent of prophylactic lymphadenectomy did not significantly affect local tumor recurrence in patients with node-negative advanced gastric cancer (X(2) = 0.458, P = 0.928). CONCLUSIONS: D2 prophylactic lymphadenectomy is appropriate for pN0 patients who were less than 60 years old, and less than D2 dissection was suitable for the older cases. PMID- 22071222 TI - Multiple double cross-section transmission electron microscope sample preparation of specific sub-10 nm diameter Si nanowire devices. AB - The ability to prepare multiple cross-section transmission electron microscope (XTEM) samples from one XTEM sample of specific sub-10 nm features was demonstrated. Sub-10 nm diameter Si nanowire (NW) devices were initially cross sectioned using a dual-beam focused ion beam system in a direction running parallel to the device channel. From this XTEM sample, both low- and high resolution transmission electron microscope (TEM) images were obtained from six separate, specific site Si NW devices. The XTEM sample was then re-sectioned in four separate locations in a direction perpendicular to the device channel: 90 degrees from the original XTEM sample direction. Three of the four XTEM samples were successfully sectioned in the gate region of the device. From these three samples, low- and high-resolution TEM images of the Si NW were taken and measurements of the NW diameters were obtained. This technique demonstrated the ability to obtain high-resolution TEM images in directions 90 degrees from one another of multiple, specific sub-10 nm features that were spaced 1.1 MUm apart. PMID- 22071223 TI - Nanoliposome-mediated FL/TRAIL double-gene therapy for colon cancer: in vitro and in vivo evaluation. AB - OBJECTIVE: To investigate the therapeutic effects of cationic nanoliposome mediated gene therapy combined with immunotherapy for colon cancer treatment. METHODS: Recombinant plasmids containing green and red fluorescent protein reporter genes were constructed using gene cloning methods. Gene-carrying cationic nanoliposomes were prepared based on the electrostatic adherence principle and then transfected into dendritic cells (DC), which were transplanted into colon cancer cells. RESULTS: Recombinant plasmids containing green or red fluorescent protein reporter genes were successfully constructed by gene cloning and confirmed by restriction enzyme digestion and sequencing. Gene-carrying cationic nanoliposomes were transfected into colon cancer cells, and good gene expression was detected. A better level of apoptosis was observed in the combined group of tyrosine kinase receptor 3 ligand (FL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), while the lowest level was detected in the control group. The parameters in the FL and TRAIL groups were between the above mentioned combined group. CONCLUSION: Cationic nanoliposomes have the advantage of being gene carriers. The joint therapeutic effects of the two genes are superior to those of a single gene. Gene therapy combined with immunotherapy has significant implications for cancer treatment. PMID- 22071224 TI - Vascular endothelial growth factor-D promotes growth, lymphangiogenesis and lymphatic metastasis in gallbladder cancer. AB - Lymph node metastasis is a major prognostic factor for patients with gallbladder cancer (GBC), and greater understanding of the molecule mechanism of lymph node metastasis in GBC is needed to improve prognosis. VEGF-D has been implicated in the control of lymphangiogenesis in many carcinomas, but the biological function of VEGF-D in human GBC remains unclear. In this study, we analyzed the role of the VEGF-D in human GBC cells and addressed the functional role of VEGF-D using a xenograft mouse model. We examined the expression of VEGF-D in three human gallbladder cancer cell lines. A lentivirus-based effective VEGF-D siRNA vector was infected into GBC NOZ cells. The effect of VEGF-D siRNA on GBC NOZ cells was investigated by cell proliferation assay and invasion assay. Furthermore, we examined the role of VEGF-D-SiRNA on GBC NOZ cells in the mice of subcutaneous and orthotopic xenograft tumor. Our results are as follows: VEGF-D mRNA and protein were expressed in all three GBC cell lines (GBC-SD, NOZ, and SGC-996). We successfully selected D-3/siRNA as the most effective siRNA to silence VEGF-D expression after four VEGF-D siRNA plasmid transfection in NOZ cells. VEGF-D mRNA and protein expression were suppressed by lentivirus-mediated D-3/siRNA. D-3-RNAi LV inhibited NOZ cells proliferation and invasion ability in vitro. D-3-RNAi-LV inhibited tumor growth and lymphangiogenesis in the NOZ cell subcutaneous xenograft model. D-3-RNAi-LV inhibited lymphangiogenesis and lymphatic metastasis in the NOZ cell orthotopic xenograft model. Furthermore, D-3-RNAi-LV inhibited tumor ascites and hepatic invasion in the NOZ cell orthotopic xenograft model. In conclusion, VEGF-D is involved and plays an important role in GBC progression, suggesting that VEGF-D may be a potential molecular target in the treatment of GBC. PMID- 22071225 TI - Massive bleeding: Are we doing our best? AB - Massive bleeding accounts for more than 50% of all trauma-related deaths within the first 48h following hospital admission and it can significantly raise the mortality rate of any kind of surgery. Despite this great clinical relevance, evidence on the management of massive bleeding is surprisingly scarce, and its treatment is often based on empirical grounds. Successful treatment of massive haemorrhage depends on better understanding of the associated physiological changes as well as on good team work among the different specialists involved in the management of such a complex condition. PMID- 22071226 TI - Plasma in Poland: Production, use and safety. PMID- 22071227 TI - Low prevalence of occult HBV infection among HIV-infected patients in Southern Spain. AB - INTRODUCTION: The aim of this study was to assess the prevalence of occult HBV infection in HIV-positive patients in a centre in Southern Spain. METHODS: The HBV serological markers were investigated in all the patients and the presence of HBV-DNA was tested by PCR in patients with isolated anti-HBc. RESULTS: An isolated anti-HBc pattern was detected in 144/520 (27.7%) patients. HBV-DNA was detected in one of these patients (0.7%). CONCLUSIONS: In Southern Spain, there is a low prevalence of occult HBV infection among HIV-infected patients, despite increasing immigration from endemic countries. PMID- 22071228 TI - Effects of gait pattern and arm swing on intergirdle coordination. AB - Mature locomotion in humans is characterized by an anti-phase coordination (moving in opposite directions) between the pelvic and the scapular girdles. This pattern involves a specific relationship between the arm and leg motion is deemed to be most flexible and dynamically efficient. Still, when the arms are involved in another task, like a field player running with a ball in the hands, locomotion is still possible. In order to probe the flexibility of the locomotor synergy, the present study aimed to determine the persistence and the strength of the coordination patterns between the pelvic and scapular girdles when no arm swing was allowed during walking and running. Relative phase, the time difference between the girdle rotations, measured the ongoing inter-girdle coordination of eight healthy participants asked to walk and run with or without arm swing. Results showed that an absence of arm swing led to a change from an anti-phase to in-phase pattern (girdles moving in the same direction) and that an increase in velocity strengthened the adopted pattern. Moreover, the frequency distribution of relative phase for all gait patterns with arm swing proved to be bimodal, indicating that the prevailing anti-phase pattern was always mixed with a noticeable proportion of in-phase coordination. The presence of the in-phase pattern in the easy, natural locomotion with arm swing manifests its persistence and its stability, perhaps pertaining to its prevalence in earlier times in ontogeny or evolution. PMID- 22071229 TI - Severity of pediatric blepharokeratoconjunctivitis in Asian eyes. AB - PURPOSE: To describe and evaluate the severity of pediatric blepharokeratoconjunctivitis in Asia. DESIGN: Retrospective case series. METHODS: Clinical records of patients diagnosed with pediatric blepharokeratoconjunctivitis at a tertiary referral center in Singapore from 1991 through 2010 were reviewed. Patients were graded as having mild (corneal involvement without scarring), moderate (corneal scarring), or severe (corneal scarring with thinning or perforation) disease based on recorded clinical findings. RESULTS: Fifty-one patients were diagnosed with pediatric blepharokeratoconjunctivitis. The mean age at presentation was 10.2 +/- 3.6 years, most patients were female (80.4%), and the mean duration of follow-up was 58.9 +/- 44.0 months. Chinese (56.9%) subjects made up most of the cases. Most subjects had moderate (56.9%), followed by severe (37.4%) and mild (5.9%), disease. Four patients (7.9%) had an associated dermatologic disease. All patients were treated with topical antibiotics, and 98% were treated with topical steroids. Nineteen (37.3%) patients received systemic antibiotic therapy, and 1 received systemic steroid therapy. Three patients required deep lamellar keratoplasty (2 tectonic and 1 optical), and 2 underwent cornea gluing alone; all 5 of them were Chinese. Patients graded as having severe disease were more likely to undergo surgical intervention (26.3%) than patients who were graded as having moderate (0%) and mild (0%) disease (P < .05). The main complication of treatment was raised intraocular pressure in 7 (13.7%) patients requiring medical therapy. Overall, best-corrected visual acuity improved by 0.10 logarithm of the minimal angle of resolution units (P < .001) after appropriate medical and surgical intervention. CONCLUSIONS: Pediatric blepharokeratoconjunctivitis patients in Asia seem to have a more severe clinical presentation and course. Early and adequate management can arrest the disease process and can minimize visual morbidity. PMID- 22071230 TI - Determinants of fixation in eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab. AB - PURPOSE: To correlate the anatomic features of the macula with functional parameters like location and stability of fixation in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. DESIGN: Retrospective analysis. METHODS: The location and stability of fixation were determined in 41 eyes of 41 patients treated with ranibizumab for neovascular age-related macular degeneration for at least 12 months. All patients underwent 3 injections of ranibizumab 1 month apart and were retreated according to predefined criteria. The fixation parameters measured with microperimetry were correlated to visual acuity, qualitative measures on optical coherence tomography, and patterns of autofluorescence. RESULTS: The location of fixation was predominantly central in 68.29%, poor central in 2.4%, and predominantly eccentric in 29.27%. The fixation was stable in 80.5%, relatively unstable in 7.3%, and unstable in 12.2%. The factors that determined central and stable location of fixation were better visual acuity (P = .004), absence of subretinal thickening (P = .003), intact subfoveal third hyperreflective band (P = .006), and intact external limiting membrane (P = .036). Autofluorescence pattern within the 4-degree circle of fovea did not correlate with fixation characteristics. However, complete absence of autofluorescence in this area was a poor prognostic indicator for central fixation. CONCLUSIONS: Anatomic characteristics of the macula determine fixation patterns in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. Further studies focused on eyes with complete absence of autofluorescence in the central 4-degree circle of fovea may help to define the disease characteristics in this group. PMID- 22071231 TI - Incomplete posterior vitreous detachment: prevalence and clinical relevance. AB - PURPOSE: To investigate the prevalence and clinical relevance of incomplete posterior vitreous detachment (PVD). DESIGN: Prospective, observational cohort study. METHODS: SETTING: Institutional. PATIENTS: Consecutive patients without previous ocular history who were diagnosed with acute uncomplicated PVD. OBSERVATIONS: Baseline kinetic ultrasound evaluation differentiated posterior vitreous separation as complete or incomplete. Prospective follow-up searched for complications related to PVD. Multivariate analysis evaluated associations of baseline demographic and clinical characteristics to incomplete PVD. A Kaplan Meier analysis evaluated the probability and its standard error of experiencing an adverse outcome. The log-rank test determined whether incomplete PVD modifies the natural history of PVD. MAIN OUTCOME MEASURES: Prevalence of incomplete PVD and the estimated incidence of late adverse outcomes such as new retinal tears, epimacular membranes, or both. RESULTS: A total of 54 of 207 patients had incomplete PVD (prevalence, 26.1%). Younger age and lattice degeneration were associated independently with incomplete PVD. After a mean follow-up of 5 years (range, 4 to 8 years), 16 patients (9.7%) experienced some adverse outcome. In 5 patients (2.7%), new retinal tears and 1 retinal detachment developed. In 12 patients (7.6%), epimacular membranes developed. Patients with incomplete PVD at baseline experienced significantly more adverse outcomes than patients with complete PVD (Kaplan-Meier estimated probability and standard error, 19.2% and 0.061 vs 5.4% and 0.02; P = .01, log-rank test). CONCLUSIONS: Up to one fourth of symptomatic, acute, and uncomplicated PVDs show incomplete posterior vitreous separation. Delayed complications related to PVD, like retinal tears and epimacular membranes, develop more frequently in patients showing incomplete PVD. PMID- 22071232 TI - Classification of early dry-type myopic maculopathy with macular choroidal thickness. AB - PURPOSE: To compare the macular choroidal thickness in 2 types of early dry-type myopic maculopathy. DESIGN: Prospective, observational, comparative study. METHODS: Patients with a refractive error of less than -8 diopters were included and were classified into 2 groups. Group 1 consisted of 24 eyes with a tessellated fundus, and group 2 consisted of 33 eyes with diffuse chorioretinal atrophy, but not to the extent of patchy chorioretinal atrophy. These 2 groups were compared with regard to their clinical characteristics, refractive error, axial length, macular choroidal thickness, and best-corrected visual acuity (BCVA). Linear regression was used to evaluate the explanatory variables in terms of macular choroidal thickness and BCVA. RESULTS: Patients in group 1 were significantly younger and had better BCVA, less myopia, shorter axial length, and less staphyloma than those in group 2. Refractive error, axial length, and BCVA correlated significantly with macular choroidal thickness in group 2. However, no such significant correlations were observed in group 1. Multiple linear regression analysis showed that age and macular choroidal thickness were the variables that associated most strongly with BCVA, whereas neither refractive error nor axial length was a significant predictor of BCVA. In group 2, eyes with lacquer cracks showed worse BCVA and thinner macular choroidal thickness than eyes without lacquer cracks. CONCLUSIONS: Macular choroidal thickness is an important factor in myopic maculopathy and can be a better indicator of its severity. These findings suggest that BCVA reduction in eyes with dry-type myopic maculopathy can be related to a thinner macular choroidal thickness and to the development of lacquer cracks. PMID- 22071233 TI - Malabsorption and nutritional balance in the ICU: fecal weight as a biomarker: a prospective observational pilot study. AB - INTRODUCTION: Malabsorption, which is frequently underdiagnosed in critically ill patients, is clinically relevant with regard to nutritional balance and nutritional management. We aimed to validate the diagnostic accuracy of fecal weight as a biomarker for fecal loss and additionally to assess fecal macronutrient contents and intestinal absorption capacity in ICU patients. METHODS: This was an observational pilot study in a tertiary mixed medical surgical ICU in hemodynamically stable adult ICU patients, without clinically evident gastrointestinal malfunction. Fecal weight (grams/day), fecal energy (by bomb calorimetry in kcal/day), and macronutrient content (fat, protein, and carbohydrate in grams/day) were measured. Diagnostic accuracy expressed in terms of test sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and receiver operator curves (ROCs) were calculated for fecal weight as a marker for energy malabsorption. Malabsorption was a priori defined as < 85% intestinal absorption capacity. RESULTS: Forty-eight patients (63 +/- 15 years; 58% men) receiving full enteral feeding were included. A cut-off fecal production of > 350 g/day (that is, diarrhea) was linked to the optimal ROC (0.879), showing a sensitivity and PPV of 80%, respectively. Specificity and NPV were both 96%. Fecal weight (grams/day) and intestinal energy-absorption capacity were inversely correlated (r = -0.69; P < 0.001). Patients with > 350 g feces/day had a significantly more-negative energy balance compared with patients with < 350 g feces/day (loss of 627 kcal/day versus neutral balance; P = 0.012). CONCLUSIONS: A fecal weight > 350 g/day in ICU patients is a biomarker applicable in daily practice, which can act as a surrogate for fecal energy loss and intestinal energy absorption. Daily measurement of fecal weight is a feasible means of monitoring the nutritional status of critically ill patients and, in those identified as having malabsorption, can monitor responses to changes in dietary management. PMID- 22071234 TI - The use of routinely collected patient data for research: a critical review. AB - Over recent years in the UK there has been growing interest in the potential for routinely collected NHS (National Health Service) patient data to be used for secondary purposes, facilitated by the potential of increasingly sophisticated electronic databases. This article is based on a critically reflective literature review which analyses the key debates pertaining to this issue. The work arose in the context of a programme of research concerning routine patient data use in neonatal care. The article includes analysis of commentary (opinion and ethical inquiry) as well as empirically derived claims. It aims to deconstruct the knowledge assumptions on which relevant research studies have been based or are proposed and it also incorporates ontological position and moral argument. Results are presented according to three predominant debates: the prevailing claim that all health research benefits civic society; the varieties of informed consent and choices open to patients regarding secondary uses of their data; and the 'rights and responsibilities' of patients when it comes to their data being used for research purposes. It examines the relevance of these themes specifically to the neonatal context and the implications for our own research, concluding that employing an alternative ethical model to the traditional professional one might be useful in order to provide a further perspective on the issue. PMID- 22071235 TI - Is elevation of the serum beta-d-glucan level a paradoxical sign for trichosporon fungemia in patients with hematologic disorders? AB - The detection of serum 1,3-beta-d-glucan (BDG) has been reported to be useful for the diagnosis and therapeutic monitoring of various invasive fungal infections. Although Trichosporon fungemia is increasingly recognized as a fatal mycosis in immunocompromised patients, the utility of this assay for Trichosporon fungemia is still unknown. In our experience (28 cases), the level of BDG rose in about half of the patients with hematologic disorders who developed Trichosporon fungemia. Among them, early death from this infection was more frequently seen in BDG-negative patients than in BDG-positive patients. In addition, overall survival was also significantly worse in BDG-negative patients than in BDG positive patients. There were no significant differences between these two patient groups in terms of clinical background. Unlike for other invasive fungal infections, elevation of BDG level may indicate a paradoxical sign for Trichosporon fungemia in patients with hematologic disorders. PMID- 22071236 TI - Tolerability of dipeptidyl peptidase-4 inhibitors: a review. AB - BACKGROUND: Oral glucose-lowering agents are used to treat patients with type 2 diabetes mellitus (T2DM). Most patients require multiple agents to maintain glycemic targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors are administered as monotherapy and in combination therapy for the treatment of T2DM. OBJECTIVE: The aim of this article was to provide a thorough review of published tolerability data on 5 DPP-4 inhibitors. METHODS: PubMed and Web of Science were searched for English-language clinical trials published from January 2000 to June 2001, using the following key words: dipeptidyl peptidase-4 inhibitor, vildagliptin, alogliptin, sitagliptin, saxagliptin, linagliptin, safety, tolerability, efficacy, effect, AE, and adverse effect. Studies were considered for inclusion if they were randomized, double-blind trials performed in patients >=18 years of age with T2DM and with a hemoglobin A(1c) of >=6.5%; included >=1 arm that received monotherapy with DPP-4; and reported adverse events (AEs). Studies in patients with a history of type 1 or secondary forms of diabetes, significant diabetic complications or cardiovascular disease within the 6 months before the start of the study, hepatic disease or abnormalities, and/or renal abnormalities were excluded. RESULTS: A total of 45 clinical trials, 5 pharmacokinetic studies, and 28 meta-analyses or reviews were included. The duration of studies ranged from 7 days to 104 weeks. The most commonly reported AEs were nasopharyngitis, upper respiratory infections, all-cause infections, headache, gastrointestinal symptoms, and musculoskeletal pain. Based on the findings from the studies, the DPP-4 inhibitors had minimal impact on weight and were not associated with an increased risk for hypoglycemia relative to placebo. Rates of nasopharyngitis were higher with the DDP-4 inhibitors than with placebo. Pancreatitis was reported at lower rates with the DPP-4 inhibitors compared with other oral antihyperglycemic agents. Cardiovascular events were limited, and postmarketing studies are ongoing. CONCLUSIONS: The tolerability of DPP-4 inhibitors is supported by published clinical trials. The rates of weight gain, gastrointestinal AEs, and hypoglycemia were minimal with the DPP-4 inhibitors studied. PMID- 22071237 TI - The economic impact and cost-effectiveness of urinary neutrophil gelatinase associated lipocalin after cardiac surgery. AB - BACKGROUND: Acute kidney injury (AKI) is common after cardiac surgery, and expeditious recognition with specific biomarkers may help improve outcome. OBJECTIVE: Because the economic impact of a biomarker-based diagnostic strategy is unknown, we assessed the cost-effectiveness of using urinary neutrophil gelatinase-associated lipocalin (NGAL) for the diagnosis of AKI after cardiac surgery compared with current diagnostic methods. METHODS: A decision analysis model was developed using the societal perspective to evaluate the cost effectiveness of NGAL. Cost per quality-adjusted life-year (QALY) was determined for NGAL and standard strategies. The base case was a 67-year-old male patient undergoing coronary artery bypass graft surgery in the United Kingdom. Multiple sensitivity analyses were performed to determine how cost-effectiveness would vary with changes in the underlying clinical and economic variables. RESULTS: The base case yielded expected costs of L4244 and 11.86 QALYs for the NGAL strategy compared with L4672 and 11.79 QALYs for the standard therapy. The cost effectiveness ratio for the NGAL strategy was L358/QALY compared with L396/QALY for the standard regimen. Cost-effectiveness increased as the treatment effect defined as the ability to prevent progression of established AKI (kidney injury or failure)-for the therapy triggered by an elevated NGAL level rose. Sensitivity analysis demonstrated that the model was most responsive to the probability of developing AKI and least sensitive to the test cost for NGAL. Probabilistic sensitivity analysis supported the NGAL strategy as the most cost-effective option. Because this study was a decision analysis model incorporating a nonspecific treatment for AKI (as opposed to an observational study or controlled trial), model structural assumptions may therefore have underestimated mortality and the likelihood of developing AKI, although these were tested in multiple sensitivity analyses. Indirect costs were also not explicitly factored. CONCLUSION: The use of urinary NGAL after cardiac surgery appears to be cost effective in the early diagnosis of AKI. PMID- 22071238 TI - Azilsartan medoxomil: a new Angiotensin receptor blocker. AB - BACKGROUND: Azilsartan medoxomil is an angiotensin receptor blocker, approved on February 25, 2011 by the US Food and Drug Administration (FDA) for hypertension management. OBJECTIVE: The purpose of this study was to review the pharmacology, pharmacokinetics, efficacy, safety profile, and role of azilsartan for hypertension management. METHODS: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines were identified from MEDLINE and Current Contents (both 1966 to August 31, 2011) using the search terms azilsartan, TAK 491, TAK-536, pharmacology, pharmacokinetics, pharmacodynamics, pharmacoeconomics, and cost-effectiveness. The FDA Web site and manufacturer prescribing information were also reviewed to identify other relevant information. RESULTS: Compared with olmesartan 40 mg daily, azilsartan 80 mg reduced mean systolic blood pressure (SBP) by an additional 2.1 mm Hg (P = 0.038), whereas azilsartan 40 mg was noninferior to olmesartan 40 mg. Azilsartan 40 mg or 80 mg added to chlorthalidone 25 mg daily significantly reduced SBP to a greater extent than did chlorthalidone alone (P < 0.05), but there was no difference between azilsartan 40 mg and 80 mg (40 mg: -31.72 mm Hg; 80 mg: -31.3 mm Hg [P > 0.05]). When coadministered with amlodipine 5 mg daily, both azilsartan 40 mg and 80 mg + amlodipine decreased SBP significantly more than amlodipine alone (amlodipine: -13.6 mm Hg; with azilsartan 40 mg: -24.79 mm Hg; with azilsartan 80 mg: -24.51 mm Hg [P < 0.05]). Compared with ramipril 10 mg daily, both azilsartan 40 mg and 80 mg resulted in significantly (P < 0.001) greater reductions in mean SBP (-20.63 and -21.24 mm Hg, respectively; ramipril: 12.22 mm Hg). The most common adverse events reported were dizziness (4%), dyslipidemia (3.3%), and diarrhea (2%). CONCLUSIONS: At the recommended dose of 80 mg once daily, azilsartan is reported to be an efficacious BP-lowering agent. With once-daily dosing and a favorable side-effect profile, azilsartan is an attractive option for the treatment of hypertension. There is a lack of data supporting the use of azilsartan for improvement in cardiovascular outcomes; therefore, azilsartan is not approved for indications other than the treatment of hypertension. PMID- 22071239 TI - Markers of extracellular matrix turnover and the development of right ventricular failure after ventricular assist device implantation in patients with advanced heart failure. AB - BACKGROUND: Cardiac extracellular matrix (ECM) is a dynamic and metabolically active collagenous network that responds to mechanical strain. The association between ECM turnover and right ventricular failure (RVF) development after left ventricular assist device (LVAD) implantation in patients with advanced heart failure (HF) was investigated. METHODS: Circulating levels of osteopontin, metalloproteinases (MMP)-2 and MPP-9, and tissue inhibitor of MMP (TIMP)-1 and TIMP-4 were measured in 61 patients at LVAD implantation and explantation and in 10 control subjects. RVF was defined as the need for RVAD, nitric oxide inhalation > 48 hours and/or inotropic support > 14 days. RESULTS: All ECM markers were elevated in patients with HF compared with controls (all p < 0.05). RVF developed in 23 patients (37.7%) on LVAD support. All ECM markers decreased on LVAD support in patients without RVF (all p < 0.05), but serum MMP-2, TIMP-1, TIMP-4, and osteopontin remained elevated in RVF patients. Multivariate analysis identified that right ventricular stroke work index (RVSWI), circulating B-type natriuretic peptide, and osteopontin were associated with RVF (all p < 0.05). Osteopontin correlated inversely with RVSWI (r = -0.44, p < 0.001). Osteopontin levels > 260 ng/ml discriminate patients who develop RVF from those without RVF (sensitivity, 83%; specificity, 82%). CONCLUSIONS: Marked elevation of osteopontin levels before LVAD placement is associated with RVF development. Persistent elevation of circulating ECM markers after LVAD implantation characterizes patients who develop RVF. These novel biomarkers would have a potential role in the prediction of RVF development in patients undergoing LVAD implantation. PMID- 22071240 TI - Relationship of right- and left-sided filling pressures in patients with advanced heart failure: a 14-year multi-institutional analysis. AB - BACKGROUND: Jugular venous pressure (JVP) is assessed to estimate volume status in patients with heart failure because right atrial pressure (RAP) reflects pulmonary capillary wedge pressure (PCWP). In a large cohort of heart failure patients spanning 14 years, we sought to further characterize the relationship between RAP and PCWP, including identifying temporal trends, to optimize estimates of PCWP by JVP. We also sought to determine whether the RAP to PCWP relationship impacts post-transplant mortality. METHODS: Hemodynamic data were obtained from 4,079 patients before cardiac transplantation. Elevated RAP was defined as >=10 mm Hg and elevated PCWP >=22 mm Hg. Hemodynamics were "concordant" when both RAP and PCWP were elevated or when both were not elevated. The frequency of concordant hemodynamics was assessed over 3 eras (1993 to 1997, 1998 to 2002, 2003 to 2007). Baseline characteristics were compared among quartiles of the ratio (RAP+1)/PCWP. The association of (RAP+1)/PCWP with 2-year mortality after cardiac transplantation was assessed using multivariate models. RESULTS: The frequency of concordant hemodynamics over time was stable (74%, 72%, 73%; p = 0.4). Increasing (RAP+1)/PCWP was associated with the following variables: female gender; cardiomyopathy etiology besides ischemic or non ischemic; prior sternotomies; and lower creatinine clearance (p < 0.01 for all). Elevated (RAP+1)/PCWP was associated with post-transplant mortality (relative risk 1.2, 95% confidence interval 1.02 to 1.37, p = 0.02). CONCLUSIONS: [corrected] RAP and PCWP remain concordant in most heart failure patients, supporting the ongoing use of JVP to estimate PCWP. Easily identifiable patient characteristics were associated with an increased RAP/PCWP ratio, and their presence should alert clinicians that PCWP may be overestimated by JVP assessment. A higher RAP/PCWP ratio was an adverse risk factor for post-cardiac transplant survival. PMID- 22071241 TI - Denitrification capacity of a landfilled refuse in response to the variations of COD/NO3--N in the injected leachate. AB - Effects of different chemical oxygen demand (COD) to nitrate concentration ratios in the injected leachate on the denitrification capacity of landfilled municipal solid waste were evaluated. Results showed that the 6-year-old refuse possessed high denitrification capacity. The nitrate reduction rate increased with the increasing COD concentration in the injected leachate. When the initial COD concentration increased to 6500 mg l(-1), nitrate reduction rate could reach up to 6.85 mg NO3--N l(-1) h(-1). At the initial biodegradable COD/NO3--N ratio lower than the stoichiometric ratio of heterotrophic denitrification, autotrophic bacteria was the dominant microbial communities for denitrification. With the increase of COD/NO3--N ratio, the primary functional denitrifier would shift from autotrophic Thiobacillus denitrificans to heterotrophic Azoarcus tolulyticus. These results suggested that the initial biodegradable COD/NO3--N ratio in the injected leachate should be adjusted to higher than 6.0 for rapid in situ denitrification of 500 mg NO3--Nl(-1). PMID- 22071242 TI - Exploiting metagenomic diversity for novel polyhydroxyalkanoate synthases: production of a terpolymer poly(3-hydroxybutyrate-co-3-hydroxyhexanoate-co-3 hydroxyoctanoate) with a recombinant Pseudomonas putida strain. AB - A metagenomic library of 2.1*10(6) clones was constructed using oil-contaminated soil from Gujarat (India). One of the fosmid clones, 40N22, encodes a polyhydroxyalkanoate synthase showing 76% identity with an Alcaligenes sp. synthase. The corresponding gene was expressed in Pseudomonas putida KT2440 DeltaphaC1 which is impaired in PHA production. The gene conferred the recombinant strain PpKT-40N22 with the ability to produce copolymers with up to 21% in medium-chain-length content. Thus, 37% and 45% of poly(3-hydroxybutyrate co-3-hydroxyvalerate) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate-co-3 hydroxyoctanoate), respectively were obtained when using sodium heptanoate and oleic acid as carbon sources. These 3-hydroxybutyrate-(3HB)-based polymers are of interest since they incorporate the properties of medium chain length polymers and thus increase the range of applications of PHAs. PMID- 22071243 TI - Treatment of tetracycline antibiotics by laccase in the presence of 1 hydroxybenzotriazole. AB - Tetracycline antibiotics are widely used in human and veterinary medicine; however, residual amounts of these antibiotics in the environment are of concern since they could contribute to selection of resistant bacteria. In this study, tetracycline (TC), chlortetracycline (CTC), doxycycline (DC) and oxytetracycline (OTC) were treated with laccase from the white rot fungus Trametes versicolor in the presence of the redox mediator 1-hydroxybenzotriazole (HBT). High performance liquid chromatography demonstrated that DC and CTC were completely eliminated after 15 min, while TC and CTC were eliminated after 1 h. This system also resulted in a complete loss of inhibition of growth of Escherichia coli and Bacillus subtilis and the green alga Pseudokirchneriella subcapitata with decreasing tetracycline antibiotic concentration. These results suggest that the laccase-HBT system is effective in eliminating tetracycline antibiotics and removing their ecotoxicity. PMID- 22071244 TI - Effects of initial lactic acid concentration, HRTs, and OLRs on bio-hydrogen production from lactate-type fermentation. AB - A batch test and continuous operation were performed to identify the effect of lactate on hydrogen production at pH 4.5. When the initial lactic acid concentration was increased from 0 to 8 g/L in the batch test, the hydrogen yield also increased from 1.41 to 1.72 mol-H2/mol-glucose. The system exhibited a long lag time and an insignificant hydrogen yield with 16 g-lactic acid/L. A continuous stirred tank reactor (CSTR) was operated at different organic loading rates (OLRs: 10, 15, 20 and 40 g/L/day) and hydraulic retention times (HRTs: 6, 12 and 24 h). At an OLR of 20 g-glucose/L/day and 12 h of HRT, the hydrogen yield was 1.2 mol-H2/mol-glucose. The yield decreased with a 24 h HRT. Even though lactate was one of the major constituents of volatile fatty acids (VFAs), hydrogen production was feasible throughout the operation. Clostridium sp. was the dominant hydrogen-producing bacteria in the system. PMID- 22071245 TI - In the arms of Morpheus. PMID- 22071246 TI - The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface. AB - The Na(+)- and Cl(-)-dependent GABA-betaine transporter (BGT1) has received attention mostly as a protector against osmolarity changes in the kidney and as a potential controller of the neurotransmitter GABA in the brain. Nevertheless, the cellular distribution of BGT1, and its physiological importance, is not fully understood. Here we have quantified mRNA levels using TaqMan real-time PCR, produced a number of BGT1 antibodies, and used these to study BGT1 distribution in mice. BGT1 (protein and mRNA) is predominantly expressed in the liver (sinusoidal hepatocyte plasma membranes) and not in the endothelium. BGT1 is also present in the renal medulla, where it localizes to the basolateral membranes of collecting ducts (particularly at the papilla tip) and the thick ascending limbs of Henle. There is some BGT1 in the leptomeninges, but brain parenchyma, brain blood vessels, ependymal cells, the renal cortex, and the intestine are virtually BGT1 deficient in 1- to 3-mo-old mice. Labeling specificity was assured by processing tissue from BGT1-deficient littermates in parallel as negative controls. Addition of 2.5% sodium chloride to the drinking water for 48 h induced a two- to threefold upregulation of BGT1, tonicity-responsive enhancer binding protein, and sodium-myo-inositol cotransporter 1 (slc5a3) in the renal medulla, but not in the brain and barely in the liver. BGT1-deficient and wild-type mice appeared to tolerate the salt treatment equally well, possibly because betaine is one of several osmolytes. In conclusion, this study suggests that BGT1 plays its main role in the liver, thereby complementing other betaine-transporting carrier proteins (e.g., slc6a20) that are predominantly expressed in the small intestine or kidney rather than the liver. PMID- 22071247 TI - A preclinical assessment of d.l-govadine as a potential antipsychotic and cognitive enhancer. AB - Tetrahydroprotoberberines (THPBs) are compounds derived from traditional Chinese medicine and increasing preclinical evidence suggests efficacy in treatment of a wide range of symptoms observed in schizophrenia. A receptor-binding profile of the THPB, d.l-govadine (d.l-Gov), reveals high affinity for dopamine and noradrenaline receptors, efficacy as a D2 receptor antagonist, brain penetrance in the 10-300 ng/g range, and thus motivated an assessment of the antipsychotic and pro-cognitive properties of this compound in the rat. Increased dopamine efflux in the prefrontal cortex and nucleus accumbens, measured by microdialysis, is observed following subcutaneous injection of the drug. d.l-Gov inhibits both conditioned avoidance responding (CAR) and amphetamine-induced locomotion (AIL) at lower doses than clozapine (CAR ED50: d.l-Gov 0.72 vs. clozapine 7.70 mg/kg; AIL ED50: d.l-Gov 1.70 vs. clozapine 4.27 mg/kg). Catalepsy is not detectable at low biologically relevant doses, but is observed at higher doses. Consistent with previous reports, acute d-amphetamine disrupts latent inhibition (LI) while a novel finding of enhanced LI is observed in sensitized animals. Treatment with d.l-Gov prior to conditioned stimulus (CS) pre-exposure restores LI to levels observed in controls in both sensitized animals and those treated acutely with d amphetamine. Finally, possible pro-cognitive properties of d.l-Gov are assessed with the spatial delayed win-shift task. Subcutaneous injection of 1.0 mg/kg d.l Gov failed to affect errors at a 30-min delay, but decreased errors observed at a 12-h delay. Collectively, these data provide the first evidence that d.l-Gov may have antipsychotic properties in conjunction with pro-cognitive effects, lending further support to the hypothesis that THPBs are a class of compounds which merit serious consideration as novel treatments for schizophrenia. PMID- 22071248 TI - Effectiveness and cost-effectiveness of first BCG vaccination against tuberculosis in school-age children without previous tuberculin test (BCG-REVAC trial): a cluster-randomised trial. AB - BACKGROUND: Neonatal BCG vaccination is part of routine vaccination schedules in many developing countries; vaccination at school age has not been assessed in trials in low-income and middle-income countries. Catch-up BCG vaccination of school-age children who missed neonatal BCG vaccination could be indicated if it confers protection and is cost-effective. We did a cluster-randomised trial (BCG REVAC) to estimate the effectiveness (efficacy given in routine settings) of school-age vaccination. METHODS: We assessed the effectiveness of BCG vaccination in school-age children (aged 7-14 years) with unknown tuberculin status who did not receive neonatal BCG vaccination (subpopulation of the BCG REVAC cluster randomised trial), between July, 1997, and June, 2006, in Salvador, Brazil, and between January, 1999, and December, 2007, in Manaus, Brazil. 763 schools were randomly assigned into BCG vaccination group or a not-vaccinated control group. Neither allocation nor intervention was concealed. Incidence of tuberculosis was the primary outcome. Cases were identified via the Brazilian Tuberculosis Control Programme. Study staff were masked to vaccination status when identified cases were linked to the study population. We estimated cost-effectiveness in Salvador by comparison of the cost for vaccination to prevent one case of tuberculosis (censored at 9 years) with the average cost of treating one case of tuberculosis. Analysis of all included children was by intention to treat. For calculation of the incidence rate we used generalised estimating equations and correlated observations over time. FINDINGS: We randomly assigned 20,622 children from 385 schools to the BCG vaccination group and 18,507 children from 365 schools to the control group. The crude incidence of tuberculosis was 54.9 (95% CI 45.3-66.7) per 100,000 person-years in the BCG vaccination group and 72.7 (62.8-86.8) per 100,000 person-years in the control group. The overall vaccine effectiveness of a first BCG vaccination at school age was 25% (3-43%). In Salvador, where vaccine effectiveness was 34% (8-53%), vaccination of 381 children would prevent one case of tuberculosis and was cheaper than treatment. The frequency of adverse events was very low with only one axillary lymphadenitis and one ulcer greater than 1 cm in 11,980 BCG vaccinations. INTERPRETATION: Vaccination of school-age children without previous tuberculin testing can reduce the incidence of tuberculosis and could reduce the costs of tuberculosis control. Restriction of BCG vaccination to the first year of life is not in the best interests of the public nor of programmes for tuberculosis control. FUNDING: UK Department for International Development, National Health Foundation. PMID- 22071249 TI - Immunogenicity of supplemental doses of poliovirus vaccine for children aged 6-9 months in Moradabad, India: a community-based, randomised controlled trial. AB - BACKGROUND: The continued presence of polio in northern India poses challenges to the interruption of wild poliovirus transmission and the management of poliovirus risks in the post-eradication era. We aimed to assess the current immunity profile after routine doses of trivalent oral poliovirus vaccine (OPV) and numerous supplemental doses of type-1 monovalent OPV (mOPV1), and compared the effect of five vaccine formulations and dosages on residual immunity gaps. METHODS: We did a community-based, randomised controlled trial of healthy infants aged 6-9 months at ten sites in Moradabad, India. Serum neutralising antibody was measured before infants were randomly assigned to a study group and given standard-potency or higher-potency mOPV1, intradermal fractional-dose inactivated poliovirus vaccine (IPV, GlaxoSmithKline), or intramuscular full-dose IPV from two different manufacturers (GlaxoSmithKline or Panacea). Follow-up sera were taken at days 7 and 28. Our primary endpoint was an increase of more than four times in antibody titres. We did analyses by per-protocol in children with a blood sample available before, and 28 days after, receiving study vaccine (or who completed study procedures). This trial is registered with Current Controlled Trials, number ISRCTN90744784. FINDINGS: Of 1002 children enrolled, 869 (87%) completed study procedures (ie, blood sample available at day 0 and day 28). At baseline, 862 (99%), 625 (72%), and 418 (48%) had detectable antibodies to poliovirus types 1, 2, and 3, respectively. In children who were type-1 seropositive, an increase of more than four times in antibody titre was detected 28 days after they were given standard-potency mOPV1 (5/13 [38%]), higher-potency mOPV1 (6/21 [29%]), intradermal IPV (9/16 [56%]), GlaxoSmithKline intramuscular IPV (19/22 [86%]), and Panacea intramuscular IPV (11/13 [85%]). In those who were type-2 seronegative, 42 (100%) of 42 seroconverted after GlaxoSmithKline intramuscular IPV, and 24 (59%) of 41 after intradermal IPV (p<0.0001). 87 (90%) of 97 infants who were type-3 seronegative seroconverted after intramuscular IPV, and 21 (36%) of 49 after intradermal IPV (p<0.0001). INTERPRETATION: Supplemental mOPV1 resulted in almost total seroprevalence against poliovirus type 1, which is consistent with recent absence of poliomyelitis cases; whereas seroprevalence against types 2 and 3 was expected for routine vaccination histories. The immunogenicity of IPV produced in India (Panacea) was similar to that of an internationally manufactured IPV (GSK). Intradermal IPV was less immunogenic. PMID- 22071250 TI - Inactivated polio vaccine and global polio eradication. PMID- 22071251 TI - New studies of BCG: implications for tuberculosis vaccines. PMID- 22071252 TI - An effort to discover the preferred conformation of the potent AMG3 cannabinoid analog when reaching the active sites of the cannabinoid receptors. AB - Most of current 3D-QSAR algorithms use alignments of compounds at the training set based on reference active ligands in the first step of the construction of the pharamacophore modeling. This first step mostly defines the success of constructed pharmacophore models. In this step, it is essential to find the bioactive conformation for solid and reliable 3D-QSAR models. Therefore, we have proceeded through different approaches for revealing the preferred conformations of Delta(8)-THC derivative AMG-3 at CB1 and CB2 receptors. In the first approach, we have applied conformational search methods in gas and in solvent phases for the ligand. The derived low energy conformers using these methodologies have been modeled through 3D-QSAR studies (first generation model). In the second approach, the low energy conformers derived from molecular docking studies have been used as input for 3D-QSAR studies (second generation model). In the current study, a new approach using MD calculations in a simulated biological environment, thus the CB receptors surrounded by a lipid bilayer environment has been used (third generation). The obtained results for different environments were compared and the approach deriving the highest statistic results was used for the generation of the novel AMG3 analogs for optimal and selective binding affinities at CB1 and CB2 receptors by the de novo drug design modeling. PMID- 22071253 TI - Synthesis, crystal structure and pharmacological evaluation of two new Cu(II) complexes of 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (benzoyl) hydrazone: a comparative investigation. AB - Two new copper(II) complexes have been synthesized by reacting 2-oxo-1,2 dihydroquinoline-3-carbaldehyde (benzoyl) hydrazone (H(2)L) with CuCl(2).2H(2)O or Cu(NO(3))(2).3H(2)O. The structures of the complexes have been determined by single crystal X-ray diffraction studies. Results obtained using spectroscopic methods strongly suggested that the ligand and its Cu(II) complexes could interact with calf thymus DNA through intercalation. In the case of protein binding, the obtained results indicated that all the three compounds could quench the intrinsic fluorescence of bovine serum albumin through static quenching process. In addition, antioxidant activity tests showed that H(2)L and its copper(II) complexes possess significant scavenging effect against free radicals. Further, the two copper(II) complexes exhibited effective cytotoxic activity against a panel of human cancer cell lines. PMID- 22071254 TI - Synthesis, anti-inflammatory activity and molecular docking studies of 2,5 diarylfuran amino acid derivatives. AB - A series of 2,5-diaryl substituted furans functionalized with several amino acids were synthesized and evaluated as the cyclooxygenases COX-1 and COX-2 enzymes inhibitors. The proline-substituted compound inhibited PGE(2) secretion by LPS stimulated neutrophils, suggesting selectivity for COX-2. Molecular docking studies in the binding site of COX-2 were performed. PMID- 22071256 TI - 1,2,3-Triazole tethered beta-lactam-chalcone bifunctional hybrids: synthesis and anticancer evaluation. AB - The manuscript describes the synthesis of novel 1,2,3-triazole tethered beta lactam-chalcone bifunctional hybrids via click chemistry approach utilizing azide alkyne cycloaddition reactions and their evaluation as anticancer agents against four human cancer cell lines. The presence of a cyclohexyl substituent at N-1 of beta-lactam ring and methoxy substituents, preferably ortho on ring A and para on ring B on chalcones markedly improved the anticancer profiles of the synthesized scaffolds with the most potent of the test compound exhibiting an IC(50) value of <1, 67.1, <1 and 6.37 MUM against A-549(lung), PC-3(prostate), THP-1(leukemia), and Caco-2(colon) cell lines, respectively. PMID- 22071255 TI - Molecular mechanism of serotonin transporter inhibition elucidated by a new flexible docking protocol. AB - The two main groups of antidepressant drugs, the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs), as well as several other compounds, act by inhibiting the serotonin transporter (SERT). However, the binding mode and molecular mechanism of inhibition in SERT are not fully understood. In this study, five classes of SERT inhibitors were docked into an outward-facing SERT homology model using a new 4D ensemble docking protocol. Unlike other docking protocols, where protein flexibility is not considered or is highly dependent on the ligand structure, flexibility was here obtained by side chain sampling of the amino acids of the binding pocket using biased probability Monte Carlo (BPMC) prior to docking. This resulted in the generation of multiple binding pocket conformations that the ligands were docked into. The docking results showed that the inhibitors were stacked between the aromatic amino acids of the extracellular gate (Y176, F335) presumably preventing its closure. The inhibitors interacted with amino acids in both the putative substrate binding site and more extracellular regions of the protein. A general structure-docking based pharmacophore model was generated to explain binding of all studied classes of SERT inhibitors. Docking of a test set of actives and decoys furthermore showed that the outward-facing ensemble SERT homology model consistently and selectively scored the majority of active compounds above decoys, which indicates its usefulness in virtual screening. PMID- 22071257 TI - Novel octahedral Pt(IV) complex with di-n-propyl-(S,S)-ethylenediamine-N,N'-di-2 (3-cyclohexyl)propanoato ligand exerts potent immunomodulatory effects. AB - We have recently reported that a novel octahedral Pt(IV) complex with di-n-propyl (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoato ligand has a potent cytotoxic effect on glioma, melanoma and fibrosarcoma cell lines. In this work, we investigated the influence of the Pt(IV) compound on immune cells. We determined its effect on the viability of spleen cells and lymph node cells and on their capability to produce interferon (IFN)-gamma and interleukin (IL)-17. Also, we researched the compound's impact on peritoneal macrophages and generation of NO in these cells. Our results show that the complex has limited influence on cell viability of immune cells, but profound inhibitory effect on the production of examined immune mediators. These results are valuable as they show that the novel Pt(IV) complex applied in concentrations which are effective against tumor cells do not affect immune cell viability. Moreover, they also imply that the complex has immunomodulatory properties. PMID- 22071258 TI - Effect of inorganic and organic ligands on the sorption/desorption of arsenate on/from Al-Mg and Fe-Mg layered double hydroxides. AB - This paper describes the sorption of arsenate on Al-Mg and Fe-Mg layered double hydroxides as affected by pH and varying concentrations of inorganic and organic ligands, and the effect of residence time on the desorption of arsenate by ligands. The capacity of ligands to inhibit the fixation of arsenate followed the sequence: nitrate=1:2) in the first 4 h and compared to patients receiving a lower ratio. Outcomes studied were associations with mortality, hours in the intensive care unit and hours of mechanical ventilation. RESULTS: Of 4164 eligible patients, 374 received a massive transfusion and 179 (49.7%) patients who did not have coagulopathy were included for analysis. There were 66 patients who received a high ratio of FFP:PRBC, and were similar in demographics and presentation to 113 patients who received a lower ratio. There was no significant difference in mortality between the two groups (p=0.80), and the FFP:PRBC ratio was not significantly associated with mortality, ICU length of stay or mechanically ventilated hours. CONCLUSIONS: A small proportion of major trauma patients received a massive blood transfusion in the absence of acute traumatic coagulopathy. Aggressive FFP transfusion in this group of patients was not associated with significantly improved outcomes. FFP transfusion carries inherent risks with substantial costs and the population most likely to benefit from a high FFP:PRBC ratio needs to be clearly defined. PMID- 22071286 TI - The potential of biodetoxification activity as a probiotic property of Lactobacillus reuteri. AB - Previous work on the metabolism of Lactobacillus reuteri ATCC 55730 anticipated a variability in the use of organic electron acceptors as a means to relieve metabolic redox problems. Therefore, investigations focusing on this unique metabolism of L. reuteri may reveal a basis for new probiotic properties. For instance, L. reuteri may use reactive aldehydes and ketones as electron acceptors to balance their redox metabolism, which opens the possibility to exploit this bacterium for in vivo bioreduction of deleterious compounds in the gastrointestinal tract (GIT). Herein we demonstrate that L. reuteri ATCC 55730 cultures on glucose are able to use furfural (1g/L), and hydroxymethylfurfural (HMF) (0.5g/L), as electron acceptors. The former enhances the growth rate by about 25% and biomass yield by 15%, whereas the latter is inhibitory. Furfural is stoichiometrically reduced to furfuryl alcohol by the culture. The conversion of furfural had no effect on the flux distribution between the simultaneously operating phosphoketolase and Embden-Meyerhof pathways, but initiated a flux to acetate production. In addition to furfural and HMF, cellular extracts showed potential to reoxidize NADH and/or NADPH with acrolein, crotonaldehyde, and diacetyl, indicating that conversion reactions take place intracellularly, however, utilization mechanisms for the latter compounds may not be present in this strain. The strain did not reduce other GIT-related reactive compounds, including acrylamide, glyoxal, and furan. PMID- 22071287 TI - A rapid procedure for the detection and isolation of enterohaemorrhagic Escherichia coli (EHEC) serogroup O26, O103, O111, O118, O121, O145 and O157 strains and the aggregative EHEC O104:H4 strain from ready-to-eat vegetables. AB - Human infections with Enterohaemorrhagic Escherichia coli strains (EHEC) as agents of Haemorrhagic Colitis (HC) and Haemolytic Uraemic Syndrome (HUS) are frequently associated with the consumption of EHEC contaminated foodstuffs of different origins. EHEC O26, O103, O111, O118, O121, O145 and O157 strains are responsible for the majority of HC and HUS cases worldwide. In May 2011, the emerging aggregative EHEC O104:H4 strain caused a large outbreak with high HUS incidence in northern Germany. Contaminated sprouted seeds were suspected to be the vehicles of transmission. The examination of vegetables retailed for raw consumption revealed low numbers of E. coli (<100 cfu/g) together with high titres of Enterobacteriaceae and Pseudomonas (approx. 5.6 * 107 cfu/g). Specific methods of EHEC detection adapted to vegetables are not yet published. Therefore, we have developed a rapid and sensitive method for detecting low EHEC contamination in vegetables (1-10 cfu/25 g) with artificially EHEC contaminated ready-to-eat salads. A 6-hour enrichment period in BRILA-broth was sufficient to detect 1-10 EHEC from spiked samples after plating 0.1 ml portions of enrichment culture on selective TBX-agar and CHROMagar STEC plates that were incubated at 44 degrees C overnight. Unlike EHEC strains, the growth of bacteria of the plant flora was substantially inhibited at 44 degrees C. DNA for real-time PCR detection of EHEC characteristic genes (stx(1), stx(2), eae, ehxA, and O-antigen associated) was prepared with bacteria grown on TBX-agar plates. The storage of EHEC inoculated salad samples for 72 h at 6 degrees C resulted in a significant reduction (mean value 14.6%) of detectable EHEC, suggesting interference of EHEC with the resident plant microflora. CHROMagar STEC was evaluated as a selective medium for the detection of EHEC strains. Growth on CHROMagar STEC was closely associated with EHEC O26:[H11], O111:[H8], O118:H16, O121:[H19], O145:[H28], O157:[H7] and aggregative EHEC O104:H4 strains and with the presence of the terB gene (tellurite resistance). TerB sequences were found in 87.2% of 235 EHEC but only in only 12.5% of 567 non-EHEC strains. EHEC strains which did not grow on CHROMagar STEC were negative for terB as frequently observed with EHEC O103:H2 (52.9%) and sorbitol-fermenting O157:NM strains (100%). The enrichment and detection method was applied in the examination of sprouted seeds incriminated as vehicles in the EHEC O104:H4 outbreak in Germany. Aggregative EHEC O104:H4 could be detected and isolated from a sample of sprouted seeds which was suspected as vector of transmission of EHEC O104 to humans. PMID- 22071288 TI - Antimicrobial resistance and resistance genes in Escherichia coli strains isolated from commercial fish and seafood. AB - The purpose of this study was to investigate the antimicrobial resistance and to characterize the implicated genes in Escherichia coli isolated from commercial fish and seafood. Fish and seafood samples (n=2663) were collected from wholesale and retail markets in Seoul, Korea between 2005 and 2008. A total of 179 E. coli isolates (6.7%) from those samples were tested for resistance to a range of antimicrobial agents. High rates of resistance to the following drugs were observed: tetracycline (30.7%), streptomycin (12.8%), cephalothin (11.7%), ampicillin (6.7%) and ticarcillin (6.1%). No resistances to amikacin, amoxicillin/clavulanic acid and cefoxitin were observed. Seventy out of 179 isolates which were resistant to one or more drugs were investigated by PCR for the presence of 3 classes of antimicrobial resistance genes (tetracycline, aminoglycosides and beta-lactams), class 1, 2 and 3 integrons. Gene cassettes of classes 1 and 2 integrons were further characterized by amplicon sequencing. The tetracycline resistance genes tetB and tetD were found in 29 (41.4%) isolates and 14 (20%) isolates, respectively. The beta-lactam resistance gene, bla(TEM) was found in 15 (21.4%) isolates. The aminoglycoside resistance gene, aadA was found in 18 (25.7%) isolates. Class 1 integron was detected in 41.4% (n=29) of the isolates, while only 2.9% (n=2) of the isolates were positive for the presence of class 2 integron. Two different gene cassettes arrangements were identified in class 1 integron-positive isolates: dfrA12-aadA2 (1.8 kb, five isolates) and aadB aadA2 (1.6 kb, four isolates). One isolate containing class 2 integron presented the dfrA1-sat-aadA1 gene cassette array. These data suggest that commercial fish and seafood may act as the reservoir for multi-resistant bacteria and facilitate the dissemination of the resistance genes. PMID- 22071289 TI - Sub-nanosecond switching of a tantalum oxide memristor. AB - We report sub-nanosecond switching of a metal-oxide-metal memristor utilizing a broadband 20 GHz experimental setup developed to observe fast switching dynamics. Set and reset operations were successfully performed in the tantalum oxide memristor using pulses with durations of 105 and 120 ps, respectively. Reproducibility of the sub-nanosecond switching was also confirmed as the device switched over consecutive cycles. PMID- 22071290 TI - Oral nutritional support in malnourished elderly decreases functional limitations with no extra costs. AB - BACKGROUND & AIMS: Older people are vulnerable to malnutrition which leads to increased health care costs. The aim of this study was to evaluate the cost effectiveness of nutritional supplementation from a societal perspective. DESIGN: This randomized controlled trial included hospital admitted malnourished elderly (>= 60 y) patients. Patients in the intervention group received nutritional supplementation (energy and protein enriched diet, oral nutritional support, calcium-vitamin D supplement, telephone counselling by a dietician) until three months after discharge from hospital. Patients in the control group received usual care (control). Primary outcomes were Quality Adjusted Life Years (QALYs), physical activities and functional limitations. Measurements were performed at hospital admission and three months after discharge. Data were analyzed according to the intention-to-treat principle and multiple imputation was used to impute missing data. Incremental cost-effectiveness ratios were calculated and bootstrapping was applied to evaluate cost-effectiveness. Cost-effectiveness was expressed by cost-effectiveness planes and cost-effectiveness acceptability curves. RESULTS: 210 patients were included, 105 in each group. After three months, no statistically significant differences in quality of life and physical activities were observed between groups. Functional limitations decreased significantly more in the intervention group (mean difference -0.72, 95% CI-1.15; -0.28). There were no differences in costs between groups. Cost-effectiveness for QALYs and physical activities could not be demonstrated. For functional limitations we found a 0.95 probability that the intervention is cost-effective in comparison with usual care for ceiling ratios > ?6500. CONCLUSIONS: A multi component nutritional intervention to malnourished elderly patients for three months after hospital discharge leads to significant improvement in functional limitations and is neutral in costs. A follow-up of three months is probably too short to detect changes in QALYs or physical activities. PMID- 22071291 TI - Prediction of all-cause mortality by B group vitamin status in the elderly. AB - BACKGROUND & AIMS: Little is known about the direct relationship of B vitamins to mortality in the elderly. All-cause mortality by vitamin B status, using dietary (B-1, B-2, niacin, B-6) or biochemical data (erythrocyte transketolase reductase, erythrocyte glutathione reductase, plasma pyridoxal-phosphate, folate and serum B 12) was evaluated. METHODS: The Taiwanese Elderly Nutrition and Health Survey (1999-2000) provided 1747 participants 65 years and over. Dietary and biochemical data were collected at baseline. Survivorship was determined until December 31, 2008. RESULTS: Survivors had higher vitamin B-1 and niacin intakes and pyridoxal phosphate and folate concentrations. Controlled for confounders, and relative to the lowest tertile of vitamin B-1 or B-6 intakes, the hazard ratios (95% confidence interval) for tertile 3 were 0.74 (0.58-0.95) and 0.74 (0.57-0.97); both p for trend values were <0.05. Further adjustment for dietary diversity led to insignificant findings. For pyridoxal-phosphate, compared to those with deficiency levels, the multivariable-adjusted hazard ratios (95% confidence interval) for adequacy was 0.52 (0.38-0.71) with p for trend <0.0001 and unchanged with dietary diversity adjustment. CONCLUSIONS: Higher vitamin B-1 and B-6 intakes and plasma pyridoxal-phosphate were associated with lower risk of mortality up to 10 years and could be achieved by increased dietary diversity. PMID- 22071292 TI - Prevalence of Borrelia burgdorferi infection in a series of 98 primary cutaneous lymphomas. AB - Borrelia burgdorferi has been variably associated with different forms of primary cutaneous lymphoma. Differences in prevalence rates among reported studies could be a result of geographic variability or heterogeneity in the molecular approaches that have been employed. In the present study, we investigated the prevalence of Borrelia burgdorferi sensu lato DNA in diagnostic tissue samples from fresh cutaneous biopsies of 98 primary cutaneous lymphomas and 19 normal skin controls. Three different polymerase chain reaction (PCR) protocols targeting the hbb, flagellin, and Osp-A genes were used. Direct sequencing of both sense and antisense strands of purified PCR products confirmed the specificity of the amplified fragments. Sequence specificity was assessed using the Basic Local Alignment Search Tool, and MultAlin software was used to investigate the heterogeneity of target gene sequences across the different samples. Borrelia DNA was not detected in 19 controls, 23 cases of follicular lymphoma, 31 cases of extranodal marginal zone lymphoma, or 30 cases of mycosis fungoides. A single case of 14 diffuse large B-cell lymphoma cases was positive for B. burgdorferi. This study does not support a pathogenic role of B. burgdorferi in primary cutaneous B- and T-cell lymphomas from areas nonendemic for this microorganism and the consequent rationale for the adoption of antibiotic therapy in these patients. PMID- 22071293 TI - [Editorial comment: Theme issue on diabetology]. PMID- 22071294 TI - [Prediction and prevention of type 1 diabetes mellitus: initial results and recent prospects]. AB - Epidemiological studies indicate that the incidence and prevalence of type 1 diabetes mellitus is rising worldwide. The increase in incidence has been most prominent in the youngest age group of childhood. Prediction of type 1a autoimmune diabetes can be established by a positive family history or by genetic, immunological or metabolic markers. Prevention of type 1 diabetes can be implemented at three different levels of pathogenesis: primary prevention in individuals without any sign of beta-cell damage, secondary prevention in individuals with signs of beta-cell destruction and tertiary prevention in patients with newly diagnosed type 1 diabetes. In recent years our knowledge of the disease pathogenesis has grown quickly, and several new prevention trials have been initiated worldwide. Immunologic intervention for type 1 diabetes will prove to be probably the most effective. PMID- 22071296 TI - [Patient education: an indispensable element of care of patients with diabetes mellitus]. AB - Diabetes is a chronic and progressive disorder that impacts upon almost every aspect of life. The number of people with diabetes is continuously growing and diabetes is associated with a high mortality rate. Diabetes education is a critical element of care of people with diabetes in order to improve clinical outcomes. The therapeutic patient education is a planned and structured program that is comprehensive in scope, flexible in content, responsive to an individual's clinical and psychological needs, and adaptable to patients' educational and cultural background. The diabetes educator should control the implementation of education and should evaluate the patient's knowledge. The educator should be trained for care of patients with chronic diseases and for education of patients with diabetes mellitus. PMID- 22071297 TI - [The Bible--through the eyes of the physician II. ]. PMID- 22071295 TI - [Incretin-based therapy for treating patients with type 2 diabetes]. AB - In the last couple of years, a new class of antidiabetic drugs became available for the clinical practice. Due to the intensive research, several new drugs reached the market. Among the incretinmimetics both the GLP-1 (glucagon like peptide-1)-receptor agonist exenatide and the GLP-1-analogue liraglutide can be used for treatment. As for incretin enhancers (dipeptidyl-peptidase-4 [DPP-4] inhibitors), sitagliptin, vildagliptin and saxagliptin are available in Hungary, linagliptin will be introduced to the market in the near future. In clinical practice, any incretin-based new drugs can be used for treating patients with type 2 diabetes, preferably in combination with metformin. The clinical experiences with these new drugs are reviewed focusing on both the benefits and the potential side-effects of the particular compounds. PMID- 22071299 TI - Inhibitory activity of novel kojic acid derivative containing trolox moiety on melanogenesis. AB - A novel kojic acid derivative containing a trolox moiety, (+/-)-5-hydroxy-4-oxo 4H-pyran-2-yl methyl 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (3a), was synthesized. The two biologically active compounds, namely, kojic acid and trolox, were conjugated via an ester bond as they are expected to behave synergistically. The antioxidant activity and the tyrosinase inhibitory activity of this novel kojic acid derivative on melanogenesis were evaluated. Compound 3a exhibited potent tyrosinase inhibitory activity and radical scavenging activity. Limited structure-activity relationship (SAR) investigations indicated that the tyrosinase inhibitory activities may originate from the kojic acid moiety, and the radical scavenging activity may be due to the phenolic hydroxyl group of trolox. Compound 3a also exhibited potent depigmenting activity in a cell-based assay. The limited SAR investigations revealed that the depigmenting activity of 3a may be due to the synergistic activities of kojic acid and its trolox moiety. PMID- 22071300 TI - Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase. AB - Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid indazole constraint of MK-6186 (2). The resulting pyridone compounds are potent inhibitors of HIV RT and have antiviral activity in cell culture that is superior to other next generation NNRTI's. PMID- 22071301 TI - Renin inhibitors for the treatment of hypertension: design and optimization of a novel series of spirocyclic piperidines. AB - The discovery and SAR of a novel series of spirocyclic renin inhibitors are described herein. It was found that by restricting the northern aromatic plate to the bioactive conformation through spirocyclization, increase in renin potency and decrease in hERG affinity could both be realized. When early members of this series were found to be potent time-dependent CYP3A4 inhibitors, two distinct strategies to address this liability were explored and this effort culminated in the identification of compound 31 as an optimized renin inhibitor. PMID- 22071302 TI - A new antifungal briarane diterpenoid from the gorgonian Junceella juncea Pallas. AB - A new 8-hydroxy briarane diterpenoid (compound 1) with antifungal activity was isolated along with known compounds (2-5) from the gorgonian coral Junceellajuncea. On the basis of spectroscopic data (1D and 2D NMR, MS), the structure of the compound 1 was established as (1S,2S,8S,9S,10S,11R,12R,14S,17R) 11,20-epoxy-14-(3-methylbutanoyl)-2,9,12-triacetoxy-8-hydroxybriar-5(16)-en-18,7 olide. Compound 1 exhibited significant activity against fungi (Aspergillus niger, Candida albicans and Penicillium notatum) but the other compounds (2-5) did not exhibit the activity against fungi. PMID- 22071303 TI - Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents. AB - In the present investigation, a series of 1,5-dimethyl-2-phenyl-4-{[(5-aryl-1,3,4 oxadiazol-2-yl)methyl]amino}-1,2-dihydro-3H-pyrazol-3-one were subjected to molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) and MolSoft (MolSoft, 2007) software, lipophilicity and solubility parameters using ALOGPS 2.1 program. The compounds followed the Lipinski 'Rule of five' were synthesized for antimicrobial and antitubercular screening as oral bioavailable drugs/leads. Maximum drug-likeness model score (0.95) was found for compound, 4a. All the synthesized compounds were characterized by IR, NMR and mass spectral analysis followed by antimicrobial and antimycobacterial screening. Among the title compounds, compound 4d showed pronounced activity against Mycobacterium tuberculosis H(37)Rv and isoniazid resistant M. tuberculosis (INHR TB) with minimum inhibitory concentrations (MICs) 0.78MUM and 1.52 MUM, respectively. The compound, 4a showed maximum activity against all bacterial strains with MIC 4-8 MUg/mL comparable to standard drug ciprofloxacin, while the compounds, 4e and 4k showed maximum antifungal activity with MIC 8-16 MUg/mL less active than standard drug fluconazole. PMID- 22071304 TI - Chemical constituents of the rhizomes of Hedychium coronarium and their inhibitory effect on the pro-inflammatory cytokines production LPS-stimulated in bone marrow-derived dendritic cells. AB - The rhizomes of Hedychium coronarium have been used for the treatment of inflammation, skin diseases, headache, and sharp pain due to rheumatism in traditional medicine. From this plant, three new labdane-type diterpenes 1-3, named coronarins G-I as well as seven known 4-10, coronarin D, coronarin D methyl ether, hedyforrestin C, (E)-nerolidol, beta-sitosterol, daucosterol, and stigmasterol were isolated. Their chemical structures were elucidated by mass, 1D and 2D-nuclear magnetic resonance spectroscopy. They were evaluated for inhibitory effects on lipopolysaccharide-stimulated production of pro inflammatory cytokines in bone marrow-derived dendritic cells. Among of them, compounds 1, 2, and 6 were significant inhibitors of LPS-stimulated TNF-alpha, IL 6, and IL-12 p40 productions with IC(50) ranging from 0.19+/-0.11 to 10.38+/-2.34 MUM. The remains of compounds showed inactivity or due to cytotoxicity. These results warrant further studies concerning the potential anti-inflammatory benefits of labdane-type diterpenes from H. coronarium. PMID- 22071305 TI - Rational design and synthesis of aminopiperazinones as beta-secretase (BACE) inhibitors. AB - Aminopiperazinone inhibitors of BACE were identified by rational design. Structure based design guided idea prioritization and initial racemic hit 18a showed good activity. Modification in decoration and chiral separation resulted in the 40 nM inhibitor, (-)-37, which showed in vivo reduction of amyloid beta peptides. The crystal structure of 18a showed a binding mode driven by interaction with the catalytic aspartate dyad and distribution of the biaryl amide decoration towards S1 and S3 pockets. PMID- 22071306 TI - Cytological screening for cervical cancer prevention. AB - Historically, the incidence and mortality of cervical cancer has declined in countries that have instituted and sustained mass-organised cytology-based screening programmes. These programmes, however, required frequent repeats of the screening tests. They also require a functioning healthcare infrastructure, with laboratories for smear processing and interpretation, mechanisms for quality control, referral for colposcopy, treatment of precursors, and follow-up to detect failures of treatment. Although this approach has been successful in preventing cervical cancer where implemented correctly, it has proved inordinately complex and expensive for developing countries. Consequently, no successful screening programmes have been established in poor countries, and cervical cancer remains the most common cancer among women in developing countries, despite the existence of cytology and the knowledge of cervical cancer prevention. New technologies, specifically the development of liquid-based cytology, have improved the performance of cytology as a screening test, but do not obviate the infrastructural challenges posed to health systems by cytology based screening programmes. In this chapter, the history of cytological screening and the challenges posed by secondary prevention strategies are reviewed. PMID- 22071308 TI - Comment on "Musculoskeletal stress marker (MSM) differences in the modern American upper limb and pectoral girdle in relation to activity level and body mass index (BMI)" by K. Godde and R. Wilson Taylor. PMID- 22071307 TI - Mitral regurgitation in patients referred for transcatheter aortic valve implantation using the Edwards Sapien prosthesis: mechanisms and early postprocedural changes. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative to conventional surgery in high-risk patients with severe aortic stenosis (AS), but data regarding mitral regurgitation (MR) characteristics and changes after TAVI are sparse. METHODS: A total of 254 patients with severe AS referred for TAVI were prospectively enrolled. Comprehensive echocardiography was performed at baseline and at 7 days and 1 month in patients who underwent TAVI. MR was semiquantitatively graded from 0 to 4. Overlap of the anterior mitral leaflet and the device was measured using transesophageal echocardiography immediately after TAVI. RESULTS: At screening, MR was absent in 26%, grade 1 in 44%, grade 2 in 25%, and grade >=3 in 5% and was organic in 68% and functional in 32%. TAVI was finally performed using the Edwards Sapien valve in 119 patients, including four with MR grade >= 3. MR grade significantly decreased at 7 days (P = .003) but remained unchanged at 1 month (P = .55), whereas reverse remodeling occurred only at 1 month (improvements in left ventricular [LV] end-systolic diameter and ejection fraction; P < .05 for both). MR changes over time significantly differed according to ejection fraction and LV diameters (all P values for interaction < .005) but not according to aortic mean gradient, MR etiology, or overlap of the anterior mitral leaflet and the device (all P values for interaction > .15). CONCLUSIONS: In patients referred for TAVI, MR is common, mainly organic, and rarely severe. After TAVI, MR improved within 7 days in both organic and functional MR, was not influenced by overlap of the anterior mitral leaflet and the device, but was associated with improvement in LV ejection fraction. Possible MR improvement should be taken into account in patient selection for TAVI especially, in cases of LV dysfunction or enlargement and MR of borderline severity. PMID- 22071309 TI - The discrimination potential of diffuse-reflectance ultraviolet-visible-near infrared spectrophotometry for the forensic analysis of paper. AB - The application of diffuse reflectance UV-VIS-NIR spectroscopy is proposed to differentiate 20 office paper samples, which had been deemed similar by a preliminary visual examination under several different lighting sources. The samples were firstly screened on the basis of the qualitative appearance of their spectra. A further discrimination was obtained by taking into account three parameters: the average reflectivity of the paper samples in the range 680-900nm, and the integrated intensity of the absorption peak in the UV range at 272nm and at 360nm. The homogeneity of these parameters on both sides of the paper sheets was assessed, detecting a very uniform distribution of the optical brighteners. A special focus was posed on the determination of the discriminative power, in order to give a quantitative parameter on the proposed procedure, which is important when reporting results to the Court. The remarkable achievement of differentiating all the examined samples was obtained by UV-VIS spectroscopy, a very less expensive technique which is readily available in practically all forensic laboratories. PMID- 22071310 TI - Comparison of extraction procedures for benzodiazepines determination in hair by LC-MS/MS. AB - INTRODUCTION: The use of a LC-MS/MS system for benzodiazepines detection remarkably increased the analytical sensitivity of these drugs in biological matrices, in particular in non-conventional ones such as hair. Since the amount of hair sample available for the analysis is frequently limited and, moreover, it needs to be checked for many other drugs and compounds of forensic interest, it is important to develop a sample preparation procedure able to detect either benzodiazepines and as many as possible other substances. The aim of this study was to compare the sensitivity of two different hair sample preparation procedures for benzodiazepines detection in hair. METHODS: About 20mg hair, previously washed with organic solvent and cut into small pieces, were ultrasonicated with a phosphate buffer (pH 8.4) up to 1h and then extracted with dichloromethane/diethyl ether. The organic solvent was then dried under nitrogen flow and samples were reconstituted with 60MUl methanol. Finally a 5MUl aliquot was injected in the LC-MS/MS system. The second procedure consisted of an ultrasonication of hair samples in 700MUl of methanol. Samples were then directly analyzed. Both the methods were fully validated. RESULTS: Thirty-five compounds among benzodiazepines and their metabolites were screened using both the procedures. The methods fulfilled all the validation parameters and were applied on either spiked blank hair and real positive samples. While phosphate extraction allowed to reach a LOQ for almost all the substances ranging from 0.1 to 5pg/mg, thus guaranteeing to evaluate even a single dose administration (as confirmed by real positive cases) the sensitivity of the methanol extraction showed a LOQ ranging from 1 to 20pg/mg, still enough to assess a therapeutic use of almost all the benzodiazepines; yet the methanolic incubation allows a simple and rapid analytical procedure due to the direct injection of the extraction solvent. CONCLUSION: Even though a methanol extraction procedure for benzodiazepines determination is useful for forensic toxicological purposes also when a wider range of substances is needed and in case of a small amount of hair available, it is advisable to prefer a phosphate extraction when detection of a single dose administration is required. PMID- 22071311 TI - Cognitive performance after postoperative pituitary radiotherapy: a dosimetric study of the hippocampus and the prefrontal cortex. AB - OBJECTIVE: The hippocampus and prefrontal cortex (PFC) are important for memory and executive functioning and are known to be sensitive to radiotherapy (RT). Radiation dosimetry relates radiation exposure to specific brain areas. The effects of various pituitary RT techniques were studied by relating detailed dosimetry of the hippocampus and PFC to cognitive performance. METHODS: In this cross-sectional design, 75 non-functioning pituitary macroadenoma (NFA) patients (61+/-10 years) participated and were divided into irradiated (RT+, n=30) and non irradiated (RT-, n=45) groups. The RT+ group (who all received 25 fractions of 1.8 Gy; total dose: 45 Gy) consisted of three RT technique groups: three-field technique, n=10; four-field technique, n=15; and five-field technique, n=5. Memory and executive functioning were assessed by standardized neuropsychological tests. A reconstruction of the dose distributions for the three RT techniques was made. The RT doses on 30, 50, and 70% of the volume of the left and right hippocampus and PFC were calculated. RESULTS: Cognitive test performance was not different between the four groups, despite differences in radiation doses applied to the hippocampi and PFC. Age at RT, time since RT, and the use of thyroid hormone varied significantly between the groups; however, they were not related to cognitive performance. CONCLUSION: This study showed that there were no significant differences on cognitive performance between the three-, four-, and five-field RT groups and the non-irradiated patient group. A dose-response relationship could not be established, even with a radiation dose that was higher on most of the volume of the hippocampus and PFC in case of a four-field RT technique compared with the three- and five-field RT techniques. PMID- 22071312 TI - Quantitative trait loci for biofortification traits in maize grain. AB - Detecting genes that influence biofortification traits in cereal grain could help increase the concentrations of bioavailable mineral elements in crops to solve the global mineral malnutrition problem. The aims of this study were to detect the quantitative trait loci (QTLs) for phosphorus (P), iron (Fe), zinc (Zn), and magnesium (Mg) concentrations in maize grain in a mapping population, as well as QTLs for bioavailable Fe, Zn, and Mg, by precalculating their respective ratios with P. Elemental analysis of grain samples was done by coupled plasma-optical emission spectrometry in 294 F(4) lines of a biparental population taken from field trials of over 3 years. The population was mapped using sets of 121 polymorphic markers. QTL analysis revealed 32 significant QTLs detected for 7 traits, of which some were colocalized. The Additive-dominant model revealed highly significant additive effects, suggesting that biofortification traits in maize are generally controlled by numerous small-effect QTLs. Three QTLs for Fe/P, Zn/P, and Mg/P were colocalized on chromosome 3, coinciding with simple sequence repeats marker bnlg1456, which resides in close proximity to previously identified phytase genes (ZM phys1 and phys2). Thus, we recommend the ratios as bioavailability traits in biofortification research. PMID- 22071313 TI - Population genetics and morphological comparisons of migratory European (Hirundo rustica rustica) and sedentary East-Mediterranean (Hirundo rustica transitiva) barn swallows. AB - Speciation processes are largely determined by the relative strength of divergent selection versus the magnitude of gene flow. The barn swallow (Hirundo rustica) has a broad geographic distribution that encompasses substantial geographic variation in morphology and behavior. The European (H. r. rustica) and East Mediterranean (H. r. transitiva) subspecies are closely related, despite differing in morphological and life-history traits. To explore patterns of genetic differentiation and gene flow, we compared morphological and genetic variation among the nonmigratory breeding population of H. r. transitiva from Israel and the migratory population of H. r. rustica that passes through Israel and compared it with the genetic differentiation between H. r. transitiva from Israel and a breeding population of H. r. rustica from the United Kingdom that uses a different migratory flyway. Mitochondrial haplotype network analysis suggests that the European and East-Mediterranean populations are intermixed, although there was low but significant genetic differentiation between the subspecies based on both mitochondrial (F(ST) = 0.025-0.033) and microsatellite (F(ST) = 0.009-0.014) loci. Coalescent-based analyses suggest recent divergence and substantial gene flow between these populations despite their differences in morphological and behavioral traits. The results suggest that these subspecies are undergoing a differentiation process in the face of gene flow, with selection possibly operating on sexually selected traits. PMID- 22071314 TI - Multiple domains of MASP-2, an initiating complement protease, are required for interaction with its substrate C4. AB - The complement system is fundamental to both innate and adaptive immunity and can be initiated via the classical, lectin or alternative pathways. Cleavage of C4 by MASP-2, the initiating protease of the lectin pathway, is a crucial event in the activation of this pathway, preceding the eventual formation of the C3 convertase (C4bC2a) complex on the pathogen surface. Interactions required for the cleavage of C4 by MASP-2 are likely to be facilitated by the initial binding of C4 to an exosite on the protease. We have shown that both proteolytically active and catalytically inactive CCP1-CCP2-serine protease (CCP1-CCP2-SP) forms bind C4 with similar affinity. Interestingly, proteins containing the CCP1-CCP2 domains or the SP domain alone bound C4 with much lower affinity than the CCP1-CCP2-SP protein, suggesting that the CCP domains cooperate positively with the active site to mediate efficient binding and cleavage of C4. In addition, mutation of residue K342 to alanine in the CCP1 domain abolished binding to both C4 and C4b in its CCP1-CCP2 form, suggesting a key electrostatic role for this amino acid. The presented data indicates that all of the domains are required in order to mediate high affinity interaction with C4. PMID- 22071315 TI - Treatment of neurogenic diabetes insipidus. AB - Central or neurogenic diabetes insipidus results from a deficiency in antidiuretic hormone (ADH) or arginine-vasopressin (AVP). Treatment is based on replacement therapy with the hormone analog desmopressin (d-DAVP). d-DAVP can be administered subcutaneously to infants or patients with postoperative or posttraumatic brain injury being monitored for transient diabetes insipidus. Intranasal and oral forms are also available. The recently introduced lyophilisate, which melts under the tongue, has replaced the tablet form (recently withdrawn from the market in France) and provides better bioavailability. Irrespective of the mode of administration, it is usually the patient who finds the effective minimal dose necessary for a normal life, i.e. without excessive polyuria, particularly at night. Patient education is necessary to avoid the risk of water intoxication and hyponatremia. PMID- 22071316 TI - Potential benefits of using cardiac gated images to reduce the dose to the left anterior descending coronary during radiotherapy of left breast and internal mammary nodes. AB - PURPOSE: To assess the benefits of using cardiac gated images for treatment planning of breast and internal mammary nodes. PATIENTS AND METHODS: Inspiration breath hold computed tomography (CT) series acquired at prospectively gated diastolic phase were used for planning. Three different techniques were compared. Technique A used tangents and an internal mammary nodes field covering the three first inter-rib spaces; technique B used an extended internal mammary nodes including part of the medial breast in junction with tangential fields; the 3(rd) technique used helical tomotherapy. For each technique, two treatment plans were performed: one plan (plan-01) where mean dose and V(25) to the heart were considered for plan evaluation and a second plan (plan-02) where the irradiation of the left anterior descending artery was minimized. RESULTS: V(25) to the heart was found to be less than 5% for all six plans. Mean doses to the heart were within 4.8 to 7.2 Gy. By attempting to lower the dose to the left anterior descending artery, heart D(mean) was decreased by 20-30% for the two techniques A and B while being unchanged for tomotherapy. Regarding target coverage, there was no marked difference between plans where only heart dose was considered (plans 01) and plans where the left anterior descending artery dose was minimized (plans 02). When the left anterior descending artery dose was part of plan evaluation, D(mean) to the left anterior descending artery could be decreased by 24, 19 and 9% for techniques A, B and tomotherapy respectively. The three techniques exposed segments of the left coronary to different levels of dose. CONCLUSION: This study showed that evaluation of the dose to the left anterior descending artery coronary may change the treatment strategy. Cardiac gated images without IV contrast permitted a good visualization of the coronaries in order to optimize the dose on these structures. In addition to heart V(25,) the dose to the coronaries should be included in prospective studies on radiotherapy related heart toxicity in association with all additional risk factors. PMID- 22071317 TI - Does age matter in song bird vocal interactions? Results from interactive playback experiments. AB - The song of oscines provides an extensively studied model of age-dependent behaviour changes. Male and female receivers might use song characteristics to obtain information about the age of a signaller, which is often related to its quality. Whereas most of the age-dependent song changes have been studied in solo singing, the role of age in vocal interactions is less well understood. We addressed this issue in a playback study with common nightingales (Luscinia megarhynchos). Previous studies showed that male nightingales had smaller repertoires in their first year than older males and males adjusted their repertoire towards the most common songs in the breeding population. We now compared vocal interaction patterns in a playback study in 12 one year old and 12 older nightingales (cross-sectional approach). Five of these males were tested both in their first and second breeding season (longitudinal approach). Song duration and latency to respond did not differ between males of different ages in either approach. In the cross-sectional approach, one year old nightingales matched song types twice as often as did older birds. Similarly, in the longitudinal approach all except one bird reduced the number of song type matches in their second season. Individuals tended to overlap songs at higher rates in their second breeding season than in their first. The higher levels of song type matches in the first year and song overlapping by birds in their second year suggest that these are communicative strategies to establish relationships with competing males and/or choosy females. PMID- 22071318 TI - Unpacking the burden: understanding the relationships between chronic pain and comorbidity in the general population. AB - We investigated the association of chronic pain with physical and mental comorbidity in the New Zealand population by measuring chronic pain status separate from comorbid conditions. Models of allostatic load provided a conceptual basis for considering multi-morbidity as accumulated comorbid load and for using both discrete conditions and cumulative measures in analyses. The nationally representative cross-sectional survey data included self-reported doctor-diagnosed chronic physical and mental health conditions, Kessler 10-item scale scores, an independent measure of chronic pain, and sociodemographic characteristics. The population prevalence of chronic pain is 16.9%, and a quarter (26%) of the population report 2 or more comorbid physical conditions statistically associated with chronic pain (unadjusted P<0.01). Results indicate that accumulated comorbid load is independently associated with chronic pain. Six physical conditions independently associated with chronic pain (adjusted odds range from 1.4 to 3.9) increase the risk of chronic pain in an additive manner, and residual accumulated load further increases risk for 2 or more conditions (adjusted odds 1.6). Anxiety/depression interacts synergistically with arthritis and neck/back disorders to increase the odds of reporting chronic pain beyond an additive model. This synergistic effect is not apparent for other conditions or for additional comorbid load. Results imply that measurement of chronic pain independent of comorbid conditions and adjustment for comorbid conditions is important for more accurate prevalence estimates and understanding relationships between conditions. Future epidemiological research might usefully incorporate independent measurement of chronic pain alongside adjustment for specific physical and mental health conditions as well as accumulated comorbid load. PMID- 22071319 TI - Galpha(q/11) signaling tonically modulates nociceptor function and contributes to activity-dependent sensitization. AB - Peripheral injury or inflammation leads to a release of mediators capable of binding to a variety of ion channels and receptors. Among these are the 7 transmembrane receptors (G protein-coupled receptors) coupling to G(s), G(i/o), G12/13, or G(q/11) G proteins. Each of the G protein-coupled receptor pathways is involved in nociceptive modulation and pain processing, but the relative contribution of individual signaling pathways in vivo has not yet been worked out. The G(q)/G11 signaling branch is of particular interest because it leads to the activation of phospholipase C-beta, protein kinase C, the release of calcium from intracellular stores, and it modulates extracellular regulated kinases. To investigate the contribution of the entire G(q/11)-signaling pathway in nociceptors towards regulation of pain, we generated double-deficient mice lacking G(q/11) selectively in nociceptors using a conditional gene-targeting approach. We observed that nociceptor-specific loss of G(q) and G11 results in reduced pain hypersensitivity following paw inflammation or spared nerve injury. Surprisingly, our behavioral and electrophysiological experiments also indicated defects in basal mechanical sensitivity in G(q/11) mutant mice, suggesting a novel function for G(q/11) in tonic modulation of acute nociception. Patch-clamp recordings revealed changes in voltage-dependent tetrodotoxin-resistant and tetrodotoxin-sensitive sodium channels in nociceptors upon a loss of G(q/11), whereas potassium currents remained unchanged. Our results indicate that the functional role of the G(q)/G11 branch of G-protein signaling in nociceptors in vivo not only spans sensitization mechanisms in pathological pain states, but is also operational in tonic modulation of basal nociception and acute pain. PMID- 22071321 TI - Ge-Si-O phase separation and Ge nanocrystal growth in Ge:SiO(x)/SiO(2) multilayers--a new dc magnetron approach. AB - Ge:SiO(x)/SiO(2) multilayers are fabricated using a new reactive dc magnetron sputtering approach. The influence of the multilayer stoichiometry on the ternary Ge-Si-O phase separation and the subsequent size-controlled Ge nanocrystal formation is explored by means of x-ray absorption spectroscopy, x-ray diffraction, electron microscopy and Raman spectroscopy. The ternary system Ge-Si O reveals complete Ge-O phase separation at 400 degrees C which does not differ significantly to the binary Ge-O system. Ge nanocrystals of < 5 nm size are generated after subsequent annealing below 700 degrees C. It is shown that Ge oxides contained in the as-deposited multilayers are reduced by a surrounding unsaturated silica matrix. A stoichiometric regime was found where almost no GeO(2) is present after annealing. Thus, the Ge nanocrystals become completely embedded in a stoichiometric silica matrix favouring the use for photovoltaic applications. PMID- 22071320 TI - Aryl hydrocarbon receptor modulation of estrogen receptor alpha-mediated gene regulation by a multimeric chromatin complex involving the two receptors and the coregulator RIP140. AB - Although crosstalk between aryl hydrocarbon receptor (AhR) and estrogen receptor alpha (ERalpha) is well established, the mechanistic basis and involvement of other proteins in this process are not known. Because we observed an enrichment of AhR-binding motifs in ERalpha-binding sites of many estradiol (E2)-regulated genes, we investigated how AhR might modulate ERalpha-mediated gene transcription in breast cancer cells. Gene regulations were categorized based on their pattern of stimulation by E2 and/or dioxin and were denoted E2-responsive, dioxin responsive, or responsive to either ligand. ERalpha, AhR, aryl hydrocarbon receptor translocator, and receptor interacting protein 140 (RIP140) were recruited to gene regulatory regions in a gene-specific and E2/dioxin ligand specific manner. Knockdown of AhR markedly increased the expression of ERalpha mediated genes upon E2 treatment. This was not attributable to a change in ERalpha level, or recruitment of ERalpha, phosphoSer5-RNA Pol II, or several coregulators but rather was associated with greatly diminished recruitment of the coregulator RIP140 to gene regulatory sites. Changing the cellular level of RIP140 revealed coactivator or corepressor roles for this coregulator in E2- and dioxin-mediated gene regulation, the choice of which was determined by the presence or absence of ERalpha at gene regulatory sites. Coimmunoprecipitation and chromatin immunoprecipitation (ChIP)-reChIP studies documented that E2- or dioxin-promoted formation of a multimeric complex of ERalpha, AhR, and RIP140 at ERalpha-binding sites of genes regulated by either E2 or dioxin. Our findings highlight the importance of cross-regulation between AhR and ERalpha and a novel mechanism by which AhR controls, through modulating the recruitment of RIP140 to ERalpha-binding sites, the kinetics and magnitude of ERalpha-mediated gene stimulation. PMID- 22071322 TI - Modeling the cultural evolution of language. AB - The paper surveys recent research on language evolution, focusing in particular on models of cultural evolution and how they are being developed and tested using agent-based computational simulations and robotic experiments. The key challenges for evolutionary theories of language are outlined and some example results are discussed, highlighting models explaining how linguistic conventions get shared, how conceptual frameworks get coordinated through language, and how hierarchical structure could emerge. The main conclusion of the paper is that cultural evolution is a much more powerful process that usually assumed, implying that less innate structures or biases are required and consequently that human language evolution has to rely less on genetic evolution. PMID- 22071323 TI - Monte Carlo simulation of pore blocking phenomena in cross-flow microfiltration. AB - An off-lattice Monte Carlo method was developed to examine the pore blocking phenomena in cross-flow microfiltration. Membranes were generated by randomly distributed pores with a given pore size distribution on a two-dimensional plane. The permeability of particles through the membrane pores was calculated, and the effects of crucial factors on the reduction of permeability were discussed. Reasonable fouling rules for simulations were examined and selected. At the initial stage the flux decreases sharply as the filtration time increases and then a steady state is reached. The results fit the pore blocking mechanism well. The simulation model developed in this study can be effectively used for analyzing a number of factors influencing physical fouling of membranes. PMID- 22071324 TI - Relationships between sand and water quality at recreational beaches. AB - Enterococci are used to assess the risk of negative human health impacts from recreational waters. Studies have shown sustained populations of enterococci within sediments of beaches but comprehensive surveys of multiple tidal zones on beaches in a regional area and their relationship to beach management decisions are limited. We sampled three tidal zones on eight South Florida beaches in Miami Dade and Broward counties and found that enterococci were ubiquitous within South Florida beach sands although their levels varied greatly both among the beaches and between the supratidal, intertidal and subtidal zones. The supratidal sands consistently had significantly higher (p < 0.003) levels of enterococci (average 40 CFU/g dry sand) than the other two zones. Levels of enterococci within the subtidal sand correlated with the average level of enterococci in the water (CFU/100mL) for the season during which samples were collected (r(s) = 0.73). The average sand enterococci content over all the zones on each beach correlated with the average water enterococci levels of the year prior to sand samplings (r(s) = 0.64) as well as the average water enterococci levels for the month after sand samplings (r(s) = 0.54). Results indicate a connection between levels of enterococci in beach water and sands throughout South Florida's beaches and suggest that the sands are one of the predominant reservoirs of enterococci impacting beach water quality. As a result, beaches with lower levels of enterococci in the sand had fewer exceedences relative to beaches with higher levels of sand enterococci. More research should focus on evaluating beach sand quality as a means to predict and regulate marine recreational water quality. PMID- 22071325 TI - Transformation of arsenic in offshore sediment under the impact of anaerobic microbial activities. AB - Sediment bound arsenic usually undergoes phase transformation processes when it is transported and buried in deeper settings. This work investigated anaerobic microbial mediated speciation change of the arsenic in offshore sediment and monitored the transformation process of oxyhydroxide associated arsenate to sulfide associated forms. The fate of arsenic and possible pathways of transformation were discussed based on quantitative analysis of aqueous and solid arsenic and iron, and qualitative characterization using X-ray absorption near edge spectroscopy (XANES). Arsenic was released and reduced upon development of anoxic conditions but was resequestered by authigenic minerals later. Most of the arsenic in the sediment was converted to orpiment-like material. Sulfide may have played double roles in arsenic redistribution process, i.e. promoting arsenic release from host oxyhydroxides in early stage and removal of arsenite from solution in the form of arsenic sulfide in later stage. The findings have implications about the pathways of arsenic transformation when arsenate is transported and buried below redox boundaries in offshore sediment. PMID- 22071326 TI - Diesel exhaust exposure and nasal response to attenuated influenza in normal and allergic volunteers. AB - RATIONALE: Diesel exhaust enhances allergic inflammation, and pollutants are associated with heightened susceptibility to viral respiratory infections. The effects of combined diesel and virus exposure in humans are unknown. OBJECTIVES: Test whether acute exposure to diesel modifies inflammatory responses to influenza virus in normal humans and those with allergies. METHODS: We conducted a double-blind, randomized, placebo-controlled study of nasal responses to live attenuated influenza virus in normal volunteers and those with allergic rhinitis exposed to diesel (100 MUg/m(3)) or clean air for 2 hours, followed by standard dose of virus and serial nasal lavages. Endpoints were inflammatory mediators (ELISA) and virus quantity (quantitative reverse-transcriptase polymerase chain reaction). To test for exposure effect, we used multiple regression with exposure group (diesel vs. air) as the main explanatory variable and allergic status as an additional factor. MEASUREMENTS AND MAIN RESULTS: Baseline levels of mediators did not differ among groups. For most postvirus nasal cytokine responses, there was no significant diesel effect, and no significant interaction with allergy. However, diesel was associated with significantly increased IFN-gamma responses (P = 0.02), with no interaction with allergy in the regression model. Eotaxin-1 (P = 0.01), eosinophil cationic protein (P < 0.01), and influenza RNA sequences in nasal cells (P = 0.03) were significantly increased with diesel exposure, linked to allergy. CONCLUSIONS: Short-term exposure to diesel exhaust leads to increased eosinophil activation and increased virus quantity after virus inoculation in those with allergic rhinitis. This is consistent with previous literature suggesting a diesel "adjuvant" effect promoting allergic inflammation, and our data further suggest this change may be associated with reduced virus clearance.Clinical trial registered with www.clinicaltrials.gov (NCT00617110). PMID- 22071327 TI - Acquisition and processing of endobronchial ultrasound-guided transbronchial needle aspiration specimens in the era of targeted lung cancer chemotherapy. AB - Recent advances in therapy for non-small cell lung carcinoma have shown that a personalized approach to treatment has the potential to significantly reduce lung cancer mortality. Concurrently, endoscopic ultrasound transbronchial needle aspiration has emerged as an accurate and sensitive tool for the diagnosis and staging of this disease. As knowledge of the molecular mechanisms that drive lung cancer progression increases, the amount of information that must be derived from a tumor specimen will also increase. Recent clinical studies have demonstrated that small specimens acquired by endoscopic ultrasound transbronchial needle aspiration are sufficient for molecular testing if specimen acquisition and processing are done with these needs in mind. Optimum use of this procedure requires a coordinated effort between the bronchoscopist and the cytopathologist to collect and triage specimens for diagnostic testing. When feasible, rapid onsite evaluation should be performed to assess the specimen for both diagnostic quality and quantity and to allocate the specimen for cell-block and possible immunohistochemistry and molecular studies. It is necessary for pulmonologists and bronchoscopists to understand the rationale for histologic and molecular testing of lung cancer diagnostic specimens and to ensure that specimens are acquired and processed in a fashion that provides information from small cytologic specimens that is sufficient to guide treatment in this era of targeted therapy. PMID- 22071328 TI - Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance. AB - RATIONALE: The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals. OBJECTIVES: We reexamined the current hypothesis using helium-3 ((3)He) magnetic resonance (MR) to assess alveolar size noninvasively between 7 and 21 years, during which lung volume nearly quadruples. If new alveolarization does not occur, alveolar size should increase to the same extent. METHODS: Lung volumes were measured by spirometry and plethysmography in 109 healthy subjects aged 7-21 years. Using (3)HeMR we determined two independent measures of peripheral airspace dimensions: apparent diffusion coefficient (ADC) of (3)He at FRC (n = 109), and average diffusion distance of helium (X(rms)) by q space analysis (n = 46). We compared the change in these parameters with lung growth against a model of lung expansion with no new alveolarization. MEASUREMENTS AND MAIN RESULTS: ADC increased by 0.19% for every 1% increment in FRC (95% confidence interval [CI], 0.13-0.25), whereas the expected change in the absence of neoalveolarization is 0.41% (95% CI, 0.31-0.52). Similarly, increase of (X(rms)) with FRC was significantly less than the predicted increase in the absence of neoalveolarization. The number of alveoli is estimated to increase 1.94-fold (95% CI, 1.64-2.30) across the age range studied. CONCLUSIONS: Our observations are best explained by postulating that the lungs grow partly by neoalveolarization throughout childhood and adolescence. This has important implications: developing lungs have the potential to recover from early life insults and respond to emerging alveolar therapies. Conversely, drugs, diseases, or environmental exposures could adversely affect alveolarization throughout childhood. PMID- 22071330 TI - Physiological risk factors for severe high-altitude illness: a prospective cohort study. AB - RATIONALE: An increasing number of persons, exposed to high altitude for leisure, sport, or work, may suffer from severe high-altitude illness. OBJECTIVES: To assess, in a large cohort of subjects, the association between physiological parameters and the risk of altitude illness and their discrimination ability in a risk prediction model. METHODS: A total of 1,326 persons went through a hypoxic exercise test before a sojourn above 4,000 m. They were then monitored up at high altitude and classified as suffering from severe high-altitude illness (SHAI) or not. Analysis was stratified according to acetazolamide use. MEASUREMENTS AND MAIN RESULTS: Severe acute mountain sickness occurred in 314 (23.7%), high altitude pulmonary edema in 22 (1.7%), and high-altitude cerebral edema in 13 (0.98%) patients. Among nonacetazolamide users (n = 917), main factors independently associated with SHAI were previous history of SHAI (adjusted odds ratios [aOR], 12.82; 95% confidence interval [CI], 6.95-23.66; P < 0.001), ascent greater than 400 m/day (aOR, 5.89; 95% CI, 3.78-9.16; P < 0.001), history of migraine (aOR, 2.28; 95% CI, 1.28-4.07; P = 0.005), ventilatory response to hypoxia at exercise less than 0.78 L/minute/kg (aOR, 6.68; 95% CI, 3.83-11.63; P < 0.001), and desaturation at exercise in hypoxia equal to or greater than 22% (aOR, 2.50; 95% CI, 1.52-4.11; P < 0.001). The last two parameters improved substantially the discrimination ability of the multivariate prediction model (C statistic rose from 0.81 to 0.88; P < 0.001). Preventive use of acetazolamide reduced the relative risk of SHAI by 44%. CONCLUSIONS: In a large population of altitude visitors, chemosensitivity parameters (high desaturation and low ventilatory response to hypoxia at exercise) were independent predictors of severe high-altitude illness. They improved the discrimination ability of a risk prediction model. PMID- 22071329 TI - CD8+ T cells provide an immunologic signature of tuberculosis in young children. AB - RATIONALE: The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis-specific CD8(+) T cells are generated in response to high bacillary loads occurring during tuberculosis. OBJECTIVES: To determine if M. tuberculosis-specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis. METHODS: Enzyme-linked immunosorbent spot assays were used to measure IFN-gamma production in response to M. tuberculosis-specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8(+) T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62). MEASUREMENTS AND MAIN RESULTS: The proportion of positive CD8(+) T-cell assays and magnitude of CD8(+) T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis-specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups. CONCLUSIONS: Among young children, M. tuberculosis-specific CD8(+) T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-gamma-producing M. tuberculosis-specific CD8(+) T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease. PMID- 22071331 TI - Overexpression of miR-125b, a novel regulator of innate immunity, in eosinophilic chronic rhinosinusitis with nasal polyps. AB - RATIONALE: Eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) represents a hard-to-treat subtype of CRS. OBJECTIVES: To determine the pattern of expression and biologic role of microRNAs (miRNAs) in CRS, particularly in eosinophilic CRSwNP. METHODS: Global miRNA expression in sinonasal mucosa from controls, CRS without nasal polyps (CRSsNP), and patients with eosinophilic CRSwNP was compared using miRNA microarrays. MiR-125b expression was detected by means of quantitative reverse-transcriptase polymerase chain reaction. The cellular localization of miR-125b was determined by in situ hybridization. MiR 125b functional assays were performed on airway epithelial cells and mice. MiR 125b expression regulation was studied by tissue and cell culture. MEASUREMENTS AND MAIN RESULTS: CRSsNP and eosinophilic CRSwNP exhibited distinct miRNA expression profiles. MiR-125b was specifically up-regulated in eosinophilic CRSwNP. MiR-125b was mainly expressed by sinonasal and bronchial epithelial cells. EIF4E-binding protein 1 (4E-BP1) was identified as a direct target of miR 125b. MiR-125b mimic or inhibitor enhanced or decreased IFN-alpha/beta production elicited by dsRNA in vitro or in vivo, respectively. 4E-BP1 expression was decreased, whereas IFN regulatory factor-7 and IFN-beta expression was increased, in eosinophilic CRSwNP. IFN-beta mRNA levels positively correlated with IL-5 mRNA levels and eosinophil infiltration in sinonasal mucosa. IFN-beta stimulated B cell-activating factor of the tumor necrosis factor family production in airway epithelial cells. miR-125b could be induced by lipopolysaccharide, dsRNA, and IL 10. CONCLUSIONS: The up-regulated expression of miR-125b may enhance type I IFN expression through suppressing 4E-BP1 protein expression in airway epithelial cells, which potentially contributes to mucosal eosinophilia in eosinophilic CRSwNP. PMID- 22071332 TI - Blood glutathione decrease in subjects carrying lamin A/C gene mutations is an early marker of cardiac involvement. AB - Dominant inherited Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B are due to mutations in the LMNA gene encoding lamin A/C and present similar life-threatening cardiac disease, the early diagnosis of which lacks reliable biomarkers. Glutathione depletion characterizes subjects with cardiac diseases of non-genetic aetiology. We examined blood glutathione in 22 LMNA-mutated subjects without altered left ventricular ejection fraction (LVEF>40%) measured by conventional echocardiography. Left and right ventricular (LV/RV) contractility was evaluated using echocardiography implemented with tissue-Doppler echography. Blood glutathione was positively correlated with LV and RV contractility (p<0.05), and was decreased by 23% in subjects with reduced LV/RV contractility compared to subjects with normal contractility. ROC analysis showed that blood glutathione reliably detected reduced LV/RV contractility (AUC 95% CI: 0.90 [0.76-1.04]; p=0.01). Blood glutathione decrease may allow the detection of reduced contractility in muscular dystrophic LMNA-mutated patients with still preserved LVEF. PMID- 22071333 TI - A critical smn threshold in mice dictates onset of an intermediate spinal muscular atrophy phenotype associated with a distinct neuromuscular junction pathology. AB - Spinal muscular atrophy (SMA) is caused by mutations/deletions within the SMN1 gene and characterized by loss of lower motor neurons and skeletal muscle atrophy. SMA is clinically heterogeneous, with disease ranging from severe to mild. Here, we identify a critical threshold of Smn that dictates onset of SMA in the intermediate Smn(2B/-) mouse model. With about 15% normal level of Smn protein, Smn(2B/-) mice display reduced body weight, motor neuron loss and motor defects. Importantly, these mice are phenotype-free until P10 with a median life expectancy of 28 days. They show neuromuscular junction (NMJ) pathology with an inter-muscular differential vulnerability and an association between pre- and post-synaptic defects. Our work suggests that increasing Smn protein levels only minimally could be of significant benefit since Smn(2B/2B) mice are phenotypically normal. Further, the finding that NMJ pathology varies between severe and intermediate SMA mouse models, suggests that future therapies be adapted to the severity of SMA. PMID- 22071335 TI - Gamma Knife, CyberKnife, TomoTherapy: gadgets or useful tools? AB - PURPOSE OF REVIEW: This review provides information and an update on stereotactic radiosurgery (SRS) equipment, with a focus on intracranial lesions and brain neoplasms. RECENT FINDINGS: Gamma Knife radiosurgery represents the gold standard for intracranial radiosurgery, using a dedicated equipment, and has recently evolved with a newly designed technology, Leksell Gamma Knife Perfexion. Linear accelerator-based radiosurgery is more recent, and originally based on existing systems, either adapted or dedicated to radiosurgery. Equipment incorporating specific technologies, such as the robotic CyberKnife system, has been developed. Novel concepts in radiation therapy delivery techniques, such as intensity modulated radiotherapy, were also developed; their integration with computed tomography imaging and helical delivery has led to the TomoTherapy system. Recent data on the management of intracranial tumors with radiosurgery illustrate the trend toward a larger use and acceptance of this therapeutic modality. SUMMARY: SRS has become an important alternative treatment for a variety of lesions. Each radiosurgery system has its advantages and limitations. The 'perfect' and ubiquitous system does not exist. The choice of a radiosurgery system may vary with the strategy and needs of specific radiosurgery programs. No center can afford to acquire every technology, and strategic choices have to be made. Institutions with large neurosurgery and radiation oncology programs usually have more than one system, allowing optimization of the management of patients with a choice of open neurosurgery, radiosurgery, and radiotherapy. Given its minimally invasive nature and increasing clinical acceptance, SRS will continue to progress and offer new advances as a therapeutic tool in neurosurgery and radiotherapy. PMID- 22071336 TI - Bibliography. Degenerative and cognitive diseases. Current world literature. PMID- 22071334 TI - Evolution of the diagnostic criteria for degenerative and cognitive disorders. AB - PURPOSE OF REVIEW: This review describes the evolution of the clinical criteria for Alzheimer's disease over the past 25 years, with special emphasis on those recently published that have incorporated the use of biomarkers. RECENT FINDINGS: One of the most important advances in the knowledge of Alzheimer's disease was the development of cerebrospinal fluid, PET and MRI biomarkers. These have shown that the Alzheimer's disease is present in cognitively normal individuals, suggesting that there is a long incubation process that precedes the onset of the symptoms. Although there are diagnostic criteria for Alzheimer's disease, the National Institute on Aging and the Alzheimer's Association has proposed a set of diagnostic criteria oriented to provide a unified vision of the pathological process from preclinical, to mild cognitive impairment, and to full-blown dementia. These new criteria take advantage of different biomarkers to support the clinical diagnosis of the different stages of the disease. SUMMARY: The new guidelines provide a definition of the dementia syndrome and core diagnostic features to be used in research and clinical practice, although they caution about the use of biomarkers, since they still require validation, and the longitudinal interaction and dynamics of these biomarkers in relationship to the manifestation of the symptoms are not fully understood. PMID- 22071338 TI - Does the eHealth Literacy Scale (eHEALS) measure what it intends to measure? Validation of a Dutch version of the eHEALS in two adult populations. AB - BACKGROUND: The Internet increases the availability of health information, which consequently expands the amount of skills that health care consumers must have to obtain and evaluate health information. Norman and Skinner in 2006 developed an 8 item self-report eHealth literacy scale to measure these skills: the eHealth Literacy Scale (eHEALS). This instrument has been available only in English and there are no data on its validity. OBJECTIVES: The objective of our study was to assess the internal consistency and the construct and predictive validity of a Dutch translation of the eHEALS in two populations. METHODS: We examined the translated scale in a sample of patients with rheumatic diseases (n = 189; study 1) and in a stratified sample of the Dutch population (n = 88; study 2). We determined Cronbach alpha coefficients and analyzed the principal components. Convergent validity was determined by studying correlations with age, education, and current (health-related) Internet use. Furthermore, in study 2 we assessed the predictive validity of the instrument by comparing scores on the eHEALS with an actual performance test. RESULTS: The internal consistency of the scale was sufficient: alpha = .93 in study 1 and alpha = .92 in study 2. In both studies the 8 items loaded on 1 single component (respectively 67% and 63% of variance). Correlations between eHEALS and age and education were not found. Significant, though weak, correlations were found between the eHEALS and quantity of Internet use (r = .24, P = .001 and r = .24, P = .02, respectively). Contrary to expectations, correlations between the eHEALS and successfully completed tasks on a performance test were weak and nonsignificant: r = .18 (P = .09). The t tests showed no significant differences in scores on the eHEALS between participants who scored below and above median scores of the performance test. CONCLUSIONS: The eHEALS was assessed as unidimensional in a principal component analysis and the internal consistency of the scale was high, which makes the reliability adequate. However, findings suggest that the validity of the eHEALS instrument requires further study, since the relationship with Internet use was weak and expected relationships with age, education, and actual performance were not significant. Further research to develop a self-report instrument with high correlations with people's actual eHealth literacy skills is warranted. PMID- 22071339 TI - Correlation of histologic grade with other clinicopathological parameters, intrinsic subtype, and patients' clinical outcome in Taiwanese women. AB - OBJECTIVE: This study aimed to reveal the relationships between histologic grade and other clinicopathologic parameters including intrinsic subtype in Taiwanese women with breast cancer. METHODS: There were 1302 women diagnosed with breast cancer recruited for this study. Histologic grade was scored according to the Nottingham-modified Bloom-Richardson grading system. RESULTS: Higher tumor grade was associated with larger tumor size (P = 0.021), a larger number of lymph node metastases (P = 0.001), advanced clinical stage (P = 0.010), higher human epithelial growth receptor-2 positivity (P < 0.001), negative estrogen receptor and progesterone receptor (P < 0.0001) status. Triple negative breast cancer (56.6%) and human epithelial growth receptor-2 (44.3%) subtypes were associated with more Grade III breast cancer in contrast to luminal A (22.3%) and B (29.9%) breast cancer. In multivariate Cox regression analysis for cancer-specific survival, histologic grade (hazard ratio = 1.78) was a significant prognostic factor. CONCLUSIONS: This study demonstrated that histologic grade is highly correlated with some valuable biomarkers and confirmed the significance of histologic grade in Taiwanese female breast cancers. PMID- 22071340 TI - Diagnostic accuracy of MRI in adults with suspect brachial plexus lesions: a multicentre retrospective study with surgical findings and clinical follow-up as reference standard. AB - OBJECTIVE: To evaluate brachial plexus MRI accuracy with surgical findings and clinical follow-up as reference standard in a large multicentre study. MATERIALS AND METHODS: The research was approved by the Institutional Review Boards, and all patients provided their written informed consent. A multicentre retrospective trial that included three centres was performed between March 2006 and April 2011. A total of 157 patients (men/women: 81/76; age range, 18-84 years) were evaluated: surgical findings and clinical follow-up of at least 12 months were used as the reference standard. MR imaging was performed with different equipment at 1.5 T and 3.0 T. The patient group was divided in five subgroups: mass lesion, traumatic injury, entrapment syndromes, post-treatment evaluation, and other. Sensitivity, specificity with 95% confidence intervals (CIs), positive predictive value (PPV), pre-test-probability (the prevalence), negative predictive value (NPV), pre- and post-test odds (OR), likelihood ratio for positive results (LH+), likelihood ratio for negative results (LH-), accuracy and post-test probability (post-P) were reported on a per-patient basis. RESULTS: The overall sensitivity and specificity with 95% CIs were: 0.810/0.914; (0.697-0.904). Overall PPV, pre test probability, NPV, LH+, LH-, and accuracy: 0.823, 0.331, 0.905, 9.432, 0.210, 0.878. CONCLUSIONS: The overall diagnostic accuracy of brachial plexus MRI calculated on a per-patient base is relatively high. The specificity of brachial plexus MRI in patients suspected of having a space-occupying mass is very high. The sensitivity is also high, but there are false-positive interpretations as well. PMID- 22071341 TI - Combining longitudinal studies showed prevalence of disease differed throughout older adulthood. AB - OBJECTIVES: Disease prevalence rates are often generalized across the older adult age range. By pooling self-reported health data from five Australian longitudinal studies of aging, we were able to present disease prevalence rates by 5-year age bands and sex. We also investigated the influence of education on prevalence at each age range and compared our observed prevalence rates with those from the 2001 National Health Survey (NHS) to see if existing data could be used to augment national estimates. STUDY DESIGN AND SETTING: We used data on 12,718 adults between 60 and 105 years of age from the Dynamic Analyses to Optimise Ageing (DYNOPTA) project. RESULTS: Hypertension and arthritis were the most prevalent diseases, with approximately 30% of males and 45% of females having either condition. Nearly all diseases were most prevalent amongst older adults in their 70s and lower for individuals in their 60s, and 80s and older. The effect of education varied by disease and older age group. Prevalence rates from DYNOPTA were generally similar to those reported by the NHS. CONCLUSION: Disease prevalence is not consistent across older adulthood. Combining longitudinal studies provided a sufficient sample to estimate precise age divisions and can be used to supplement national estimates for specific populations. PMID- 22071342 TI - Medical journal editors lacked familiarity with scientific publication issues despite training and regular exposure. AB - OBJECTIVE: To characterize medical editors by determining their demographics, training, potential sources of conflict of interest (COI), and familiarity with ethical standards. STUDY DESIGN AND SETTING: We selected editors of clinical medical journals with the highest annual citation rates. One hundred eighty-three editors were electronically surveyed (response rate, 52%) on demographics and experiences with editorial training, publication ethics, industry, and scientific publication organizations. RESULTS: Editors reported formal (76%) and informal (89%) training in medical editing topics. Most editors saw publication ethics issues (e.g., authorship, COIs) at least once a year. When presented with four questions about editorial issues discussed in commonly cited authoritative policy sources, performance was poor on topics of authorship (30% answered correctly), COI (15%), peer review (16%), and plagiarism (17%). Despite this, confidence level in editorial skills on a Likert scale from the beginning to the end of the survey dropped only slightly from 4.2 to 3.9 (P<0.0001). CONCLUSION: Our study presents a current look at editors of major clinical medical journals. Most editors reported training in medical editing topics, saw ethical issues regularly, and were aware of scientific publication organizations, but their knowledge of four common and well-disseminated publication ethics topics appears poor. PMID- 22071343 TI - Methanogenic archaea are globally ubiquitous in aerated soils and become active under wet anoxic conditions. AB - The prototypical representatives of the Euryarchaeota--the methanogens--are oxygen sensitive and are thought to occur only in highly reduced, anoxic environments. However, we found methanogens of the genera Methanosarcina and Methanocella to be present in many types of upland soils (including dryland soils) sampled globally. These methanogens could be readily activated by incubating the soils as slurry under anoxic conditions, as seen by rapid methane production within a few weeks, without any additional carbon source. Analysis of the archaeal 16S ribosomal RNA gene community profile in the incubated samples through terminal restriction fragment length polymorphism and quantification through quantitative PCR indicated dominance of Methanosarcina, whose gene copy numbers also correlated with methane production rates. Analysis of the delta(13)C of the methane further supported this, as the dominant methanogenic pathway was in most cases aceticlastic, which Methanocella cannot perform. Sequences of the key methanogenic enzyme methyl coenzyme M reductase retrieved from the soil samples before incubation confirmed that Methanosarcina and Methanocella are the dominant methanogens, though some sequences of Methanobrevibacter and Methanobacterium were also detected. The global occurrence of only two active methanogenic archaea supports the hypothesis that these are autochthonous members of the upland soil biome and are well adapted to their environment. PMID- 22071344 TI - Spotlight on the Thaumarchaeota. PMID- 22071345 TI - The Western English Channel contains a persistent microbial seed bank. AB - Robust seasonal dynamics in microbial community composition have previously been observed in the English Channel L4 marine observatory. These could be explained either by seasonal changes in the taxa present at the L4 site, or by the continuous modulation of abundance of taxa within a persistent microbial community. To test these competing hypotheses, deep sequencing of 16S rRNA from one randomly selected time point to a depth of 10,729,927 reads was compared with an existing taxonomic survey data covering 6 years. When compared against the 6 year survey of 72 shallow sequenced time points, the deep sequenced time point maintained 95.4% of the combined shallow OTUs. Additionally, on average, 99.75%+/ 0.06 (mean+/-s.d.) of the operational taxonomic units found in each shallow sequenced sample were also found in the single deep sequenced sample. This suggests that the vast majority of taxa identified in this ecosystem are always present, but just in different proportions that are predictable. Thus observed changes in community composition are actually variations in the relative abundance of taxa, not, as was previously believed, demonstrating extinction and recolonization of taxa in the ecosystem through time. PMID- 22071346 TI - Analysis of the community structure of abyssal kinetoplastids revealed similar communities at larger spatial scales. AB - Knowledge of the spatial scales of diversity is necessary to evaluate the mechanisms driving biodiversity and biogeography in the vast but poorly understood deep sea. The community structure of kinetoplastids, an important group of microbial eukaryotes belonging to the Euglenozoa, from all abyssal plains of the South Atlantic and two areas of the eastern Mediterranean was studied using partial small subunit ribosomal DNA gene clone libraries. A total of 1364 clones from 10 different regions were retrieved. The analysis revealed statistically not distinguishable communities from both the South-East Atlantic (Angola and Guinea Basin) and the South-West Atlantic (Angola and Brazil Basin) at spatial scales of 1000-3000 km, whereas all other communities were significantly differentiated from one another. It seems likely that multiple processes operate at the same time to shape communities of deep-sea kinetoplastids. Nevertheless, constant and homogenous environmental conditions over large spatial scales at abyssal depths, together with high dispersal capabilities of microbial eukaryotes, maintain best the results of statistically indistinguishable communities at larger spatial scales. PMID- 22071347 TI - The energy-diversity relationship of complex bacterial communities in Arctic deep sea sediments. AB - The availability of nutrients and energy is a main driver of biodiversity for plant and animal communities in terrestrial and marine ecosystems, but we are only beginning to understand whether and how energy-diversity relationships may be extended to complex natural bacterial communities. Here, we analyzed the link between phytodetritus input, diversity and activity of bacterial communities of the Siberian continental margin (37-3427 m water depth). Community structure and functions, such as enzymatic activity, oxygen consumption and carbon remineralization rates, were highly related to each other, and with energy availability. Bacterial richness substantially increased with increasing sediment pigment content, suggesting a positive energy-diversity relationship in oligotrophic regions. Richness leveled off, forming a plateau, when mesotrophic sites were included, suggesting that bacterial communities and other benthic fauna may be structured by similar mechanisms. Dominant bacterial taxa showed strong positive or negative relationships with phytodetritus input and allowed us to identify candidate bioindicator taxa. Contrasting responses of individual taxa to changes in phytodetritus input also suggest varying ecological strategies among bacterial groups along the energy gradient. Our results imply that environmental changes affecting primary productivity and particle export from the surface ocean will not only affect bacterial community structure but also bacterial functions in Arctic deep-sea sediment, and that sediment bacterial communities can record shifts in the whole ocean ecosystem functioning. PMID- 22071348 TI - Fabrication and material properties of fibrous PHBV scaffolds depending on the cross-ply angle for tissue engineering. AB - Fibrous PHBV cross-ply scaffolds were fabricated using the electrospinning technique. The electrospun fibers were arranged depending on angles of alignment, which were 180 degrees , 90 degrees , 60 degrees , and 45 degrees . The stress and strain values of the fibrous PHBV cross-ply scaffolds increased as the cross ply angle increased. At 180 degrees , the strength and strain values of the fibers depended on tensile loading directions. At an alignment of 90 degrees , the PHBV scaffolds had a stress value of 3.5 MPa, which was more than two times higher than the random structure. The cell morphology and proliferation of L-929 cells was strongly dependant on the fiber alignment and the best results were observed when the angle alignment was high. The results of this study showed that the cross-ply structure of the PHBV scaffold affected not only the cell adhesion and spreading properties but also dictated the mechanical properties, which were dependent on the angles of alignment. PMID- 22071349 TI - Alveolar bone regeneration using poly-(lactic acid-co-glycolic acid-co-epsilon caprolactone) porous membrane with collagen sponge containing basic fibroblast growth factor: an experimental study in the dog. AB - The aim of this study was to evaluate the effects of combining porous poly-lactic acid-co-glycolic acid-co-epsilon-caprolactone (PLGC) as a barrier membrane and collagen sponge containing basic fibroblast growth factor (bFGF) to promote bone regeneration in the canine mandible. In six beagle dogs, two lateral bone defects per side were created in the mandible. The lateral bone defects on the left side were treated with a PLGC membrane plus a collagen sponge containing bFGF. In half of these, the collagen sponge contained 50 ug of bFGF. In the other half, it contained 250 ug of bFGF. As a control, we treated the right-side bone defects in each animal with the same PLGC membrane but with a collagen sponge containing phosphate buffered saline. Computed tomography (CT) images were recorded at 3 and 6 months post-op to evaluate regeneration of the bone defects. After a healing period of 6 months, whole mandibles were removed for micro-CT and histological analyses. The post-op CT images showed that more bone had formed at all experimental sites than at control sites. At 3 months post-op, the volume of bone at defect sites covered with PLGC membrane plus 250 ug of bFGF was significantly greater than it was at defect sites covered with PLGC membrane plus 50 ug of bFGF. At 6 months post-op, however, this difference was smaller and not statistically significant. Micro-CT measurement showed that the volume of new bone regenerated at bone-defect sites, covered with PLGC membrane plus bFGF, was significantly greater than that of control sites. However, the presence or absence of bFGF in the collagen sponge did not significantly affect the bone density of new bone. These results suggest that the macroporous bioresorbable PLGC membrane plus collagen sponge containing bFGF effectively facilitates healing in GBR procedures. PMID- 22071350 TI - Fabrication and biocompatibility of novel bilayer scaffold for skin tissue engineering applications. AB - In this study, a novel bilayer scaffold composed of electrospun polycaprolactone and poly(lacto-co-glycolic acid) (PCL/PLGA) membrane and glutaraldehyde (3.5% v/v) cross-linked chitosan/gelatin hydrogel was fabricated using two methods: electrospinning of the membrane onto the lyophilized hydrogel (BS-1) and membrane underlaying and casting method (BS-2). The morphology of the fabricated scaffolds was examined by scanning electron microscope (SEM). Mechanical strength, porosity, swelling capacity, and biodegradation rates of the scaffolds were also characterized. The in vitro biocompatibility of the materials was investigated by assessing cytotoxicity and cell proliferation on the material was measured using MTT assay. In addition, cell adhesion on the material was investigated by SEM. The BS-2 was grafted in Sprague-Dawley rats to determine its in vivo behavior and biocompatibility. The experimental results showed that the addition of the membrane layer to the hydrogel decreased swelling and degradation rates and provided ease of handling during implantation. Grafted BS-2 showed normal wound healing and no major inflammatory reaction was observed. PMID- 22071351 TI - Effect of ionic products of dicalcium silicate coating on osteoblast differentiation and collagen production via TGF-beta1 pathway. AB - In this work, the medium containing ionic products of dicalcium silicates (Ca(2)SiO(4)) for culturing MG63 cells was prepared by immersing a titanium alloy plate with the plasma sprayed Ca(2)SiO(4) coatings in DMEM solution. The effect of the ionic products on cellular differentiation, collagen production, and local growth factors (prostaglandin E(2) [PGE(2)] and transforming growth factor-beta [TGF-beta1]) of osteoblast-like MG63 cells were investigated. The normal DMEM was also used to culture MG63 cells as the control group. Differentiation of cell was evaluated by detecting alkaline phosphatase (ALP) activity and osteocalcin (OC) synthesis as well as their gene expression. Collagen production was analyzed by Sircol assay. The levels of PGE(2) and TGF-beta1 in culture medium were measured using enzyme-linked immunosorbent assay (ELISA). The gene expressions of TGF-beta receptors (TGF-beta RI and TGF-beta RII) were also measured by real-time PCR technology. MG63 cells cultured in DMEM containing ionic products of Ca(2)SiO(4) coating showed enhanced differentiation and increased collagen production. The results obtained from ELISA showed that the levels of PGE(2) and TGF-beta1 in experimental group were higher than that in control. The gene expression of TGF beta receptors was upregulated, indicating that more TGF-beta1 bonded to their receptors which produce more effects on the osteoblastic activity, leading to enhanced differentiation and synthetic activity of osteoblast. It is concluded that ionic products of Ca(2)SiO(4) coating may enhance cellular differentiation and collagen production by influencing TGF-beta1 pathway. PMID- 22071353 TI - Cytotoxicity of release products from magnetic nanocomposites in targeted drug delivery. AB - The efficacy of chemotherapy can be significantly improved if the therapeutic agent remains localized at the afflicted area and released at controlled rates. Such a targeted drug delivery can be achieved using magnetic nanocomposite (MNC), which incorporates drug and magnetic nanoparticles in biodegradable polymer microspheres. Reported here are results from an in vitro study on drug release rate and cytotoxicity of other release products from MNC. The model system contains an anti-cancer chemotherapy agent 5-flurouracil (5-FU) and (Co(0.5)Zn(0.5))Fe(2)O(4) in poly(lactic-co-glycolic acid) (PLGA) matrix produced by an oil/oil emulsion technique. Cell proliferation data indicate a sustained release of 5-FU for mouse macrophage cell eradication, whereas other microsphere components of magnetic nanoparticles and PLGA have little cytotoxic effects. PMID- 22071352 TI - Composite PLA scaffolds reinforced with PDO fibers for tissue engineering. AB - Novel composite scaffolds were produced using long continuous bidirectional fibers embedded in an electrospun matrix, with the aim of using them in soft tissue engineering applications. The fibers are of polydioxanone and the matrix of polylactic acid. The novel manufacturing method consists of direct electrospinning performed on both sides of a collector that supports the already arranged fibers. The scaffolds were tested in vitro using 3T3 mouse fibroblasts as-obtained or functionalized with biotin or poly (dopamine). Functionalization did not significantly affect cells attachment, metabolic activity, or proliferation, but poly (dopamine) was proven to be effective in inducing hydrophilicity to the surface. PMID- 22071355 TI - Experimental antibacterial and mineralizing calcium phosphate-based treatment for dentin surfaces. AB - OBJECTIVES: This study aimed to determine the efficacy of experimental calcium phosphate-based solutions (sCaP) containing fluoride (F), with and without zinc (Zn) ions on reducing susceptibility to acid dissolution and Streptococcus mutans (S. mutans) colonization of dentin surfaces. METHODS: Dentin sections were treated with double distilled water (control) and with sCaP solutions differing in pH and in F(-) and/or Zn(2+) ion concentrations. Solutions A (pH 7); B, C, and D (pH 5.5); solution C, twice Zn(2+) and F(-) ion concentration compared to B; solution D is similar to C but without Zn(2+). The dentin surfaces were characterized using scanning electron microscopy (SEM), x-ray diffraction, and Fourier Transform Infrared spectroscopy. Dissolution was determined in acidic buffer. Bacterial (S. mutans) attachment and growth were evaluated using SEM and Bioquant. Statistical analyses applied analysis of variance (ANOVA) and Duncan's multiple Range test. RESULTS: Compared to control, dentin surfaces treated with sCaP solutions showed: (a) occluded dentin tubules; (b)reduced susceptibility to acid dissolution; and (c) Zn(2+) ions were more effective than F(-) ions in inhibiting bacterial colonization. SIGNIFICANCE: Acidic sCaP containing both F and Zn ions have mineralizing, acid resistance, and antibacterial effects and may be potentially useful as a strategy against dentin caries formation and progression. PMID- 22071354 TI - Effects of biodegradable Mg-6Zn alloy extracts on cell cycle of intestinal epithelial cells. AB - In this study, intestinal epithelial cells (IEC)-6 were cultured in different concentration extracts of Mg-6Zn alloys for different time periods. We studied the indirect effects of Mg-6Zn alloys on cell cycle of IEC-6 cells. The cell cycle of IEC-6 cells was measured using flow cytometry. And, the cell cycle of IEC-6 cells was evaluated by investigating the expression of cyclin D1, CDK4, and P21 using real-time polymerase chain reaction (PCR) and Western blotting tests. It was found that the IEC-6 cells displayed better cell functions in 20% extract of the Mg-6Zn alloy extracts, compared to the 100% or 60% extract. The in vitro results indicated that the conspicuous alkaline environment that is a result of rapid corrosion of Mg-6Zn alloys is disadvantageous to cell cycle of IEC-6 cells. PMID- 22071356 TI - The impact of optimality on maternal sensitivity in mothers with substance abuse and psychiatric problems and their infants at 3 months. AB - The main aim of this study was to investigate the predictive validity of four different optimality indexes, as well as infant perinatal status, in relation to maternal sensitivity in interaction at 3 months. The four optimality indexes comprised items related to substance abuse, psychiatric condition, relational experience and socioeconomic status (SES). Maternal sensitivity in mother-infant interaction was assessed in two different groups of mothers. One group consisted of mothers with substance abuse and psychiatric problems who underwent treatment during pregnancy. The other group of mothers had neither substance abuse nor psychiatric problems. The expectant mothers were interviewed in the third trimester of pregnancy. Medical records and meconium were obtained from the infants at birth. Three months after birth, maternal sensitivity in mother-infant interaction was assessed. Altogether 79 mother-infant dyads participated in the study. The mothers' optimality associated with relational experiences, as well as the infants' perinatal status were found to predict maternal sensitivity in mother-infant interaction at 3 months. The SES index was also significantly related to maternal sensitivity. The relation between group and maternal sensitivity was mediated by the mothers' optimality associated with relational experiences. This study points to the importance of addressing the mothers' own relational experiences and their current representations of motherhood during treatment, in order to support and enhance maternal sensitivity. PMID- 22071357 TI - Vitamin D deficiency and endothelial dysfunction in non-dialysis chronic kidney disease patients. AB - BACKGROUND: Cardiovascular (CV) events are common in patients with chronic kidney disease (CKD) but inadequately explained by traditional risk factors. Vitamin D deficiency is highly prevalent in CKD and has been proposed to be a non traditional risk factor, but its relationship with vascular function is unknown. METHODS AND RESULTS: The aim of this study was to investigate the relationship between vitamin D levels and endothelial function in non-diabetes patients with mild to moderate CKD. Endothelial function was measured non-invasively using brachial artery flow mediated dilation (FMD). 25 hydroxy vitamin D levels were measured using electrochemiluminescence immunoassay. In 50 CKD patients (age 56+/ 11 years, BMI 25+/-4kg/m(2), 46% females, 14% smokers, 86% hypertensives, 52% with dyslipidaemia) the mean vitamin D level was 53+/-33nmol/L (21+/-13ng/L). The mean FMD was 3.8+/-2.4%. Decreasing 25 hydroxy vitamin D levels were associated with decreasing FMD [r=0.44, p=0.001]. In multivariate analysis the association remained independent after adjustment with traditional risk factors (adjusted beta 0.451; t=3.46; p<0.002). Patients with low vitamin D (<=37.5nmol/L) demonstrated low FMD compared to patients with vitamin D values >37.5nmol/L (4.4+/-2.5% vs. 2.5+/-1.6%; p=0.007); however the traditional risk factors were similar between the two groups. CONCLUSION: This is the first demonstration of an association of vitamin D deficiency with abnormal vascular endothelial function in non-dialysis CKD patients. Further studies with intervention and exploration of the mechanism are needed to establish a cause effect relationship. PMID- 22071358 TI - Lipid rafts: a signalling platform linking lipoprotein metabolism to atherogenesis. AB - Lipid rafts are microdomains of the plasma membrane which are enriched in cholesterol and sphingolipids. They serve as a platform for signal transduction, in particular during immune and inflammatory responses. As hypercholesterolemia and inflammation are two key elements of atherogenesis, it is conceivable that the cholesterol and cholesterol oxide content of lipid rafts might influence the inflammatory signalling pathways, thus modulating the development of atherosclerosis. In support of this emerging view, lipid rafts have been shown to be involved in several key steps of atherogenesis, such as the oxysterol-mediated apoptosis of vascular cells, the blunted ability of high density lipoproteins (HDL) to exert anti-inflammatory effects, and the exacerbated secretion of pro inflammatory cytokines by immune cells. Additional studies are now required to address the relative contribution of lipid raft abnormalities to the pathophysiology of atherosclerosis and cardiovascular disease. PMID- 22071359 TI - Association between cytochrome P450 2C19 polymorphism and clinical outcomes in Chinese patients with coronary artery disease. AB - BACKGROUND: Cytochrome P450 (CYP)2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which play a key role in regulating vascular tone. The aim of this study was to investigate whether the genetic functional variant 681G>A (*2) of cytochrome CYP2C19 is associated with adverse cardiovascular outcomes in Chinese patients with coronary artery disease (CAD). METHODS: Between July 2008 and September 2009, 654 consecutive patients with CAD were enrolled in this study. All participants underwent CYP2C19 genotyping. The primary study endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Secondary endpoints included the components of the primary endpoint, death from any cause, and recurrent revascularization. RESULTS: The baseline characteristics were well-balanced between carriers (heterozygous *1/*2, n=291; homozygous *2/*2, n=57) and non-carriers (n=306) of the CYP2C19*2 variant. During the follow-up period (11.42+/-4.23 months), the primary endpoint occurred more frequently in homozygous *2/*2 than in non-carriers (n=306) of CYP2C19*2 variant (12.28% versus 3.27%; adjusted hazard ratio [HR]=5.191; 95% confidence interval [CI]=1.936-13.917; P=0.001); however, no such increase was evident in heterozygous *1/*2 patients (4.12% versus 3.27%; adjusted HR=1.208; 95% CI 0.517 2.822; P=0.662). CONCLUSIONS: The homozygous CYP2C19*2/*2 genotype is an independent determinant of adverse vascular events in Chinese patients with CAD. PMID- 22071360 TI - Interaction of apolipoprotein E genotype with smoking and physical inactivity on coronary heart disease risk in men and women. AB - OBJECTIVE: Apolipoprotein E genotype (APOE) polymorphism affects lipid levels and coronary heart disease (CHD) risk. However, these associations may be modified by lifestyle factors. Therefore, we studied whether smoking, physical inactivity or overweight interact with APOE on cholesterol levels and CHD risk. METHODS: Combining two Swedish case-control studies yielded 1735 CHD cases and 4654 population controls (3747 men, 2642 women). Self-reported questionnaire lifestyle data included smoking (ever [current or former regular] or never) and physical inactivity (mainly sitting leisure time). We obtained LDL cholesterol levels and APOE genotypes. CHD risk was modelled using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for relevant covariates. RESULTS: Smoking interacted with APOE on CHD risk; adjusted ORs for ever versus never smoking were 1.45 (95% CI 1.00-2.10) in E2 carriers, 2.25 (95% CI 1.90-2.68) in E3 homozygotes and 2.37 (95% CI 1.85-3.04) in E4 carriers. Female E4 carriers had OR 3.62 (95% CI 2.32-5.63). The adjusted ORs for physical inactivity were 1.09 (95% CI 0.73-1.61), 1.34 (95% CI 1.12-1.61), and 1.79 (95% CI 1.38-2.30) in E2, E3E3 and E4 groups, respectively. No interaction was seen between overweight and APOE for CHD risk, or between any lifestyle factor and APOE for LDL cholesterol levels. CONCLUSION: The APOE E2 allele counteracted CHD risk from smoking in both genders, while the E4 allele was seen to potentiate this risk mainly in women. Similar E2 protection and E4 potentiation was suggested for CHD risk from physical inactivity. PMID- 22071361 TI - Evaluation of the online-presence (homepage) of burn units/burn centers in Germany, Austria and Switzerland. AB - PURPOSE: A successful online presence is an important key factor in the competition among hospitals today. However, little is known about the internet presence and the quality of websites of burn units on the World Wide Web. The aim was to assess the online presence of hospitals provided by specialized burn units in German speaking countries with a focus on the rate and the performance of actively run websites. METHODS: A multicenter, observational, cross-sectional study was performed over a period of 1.5 month (October-December 2010). Forty four burn units were assessed by using a previously generated criteria list. The list included 36 criteria with following topics: "research and teaching"; "patient care"; "clinical emphases", "general information"; "information brokerage". RESULTS: Overall, the websites examined offered a good overview about their different online services with many multimedia-based elements included. All websites consisted of hyperlinks, general multimedia-based elements and information on means of communication with the hospital, respectively. In contrast, the quality of specific information for burn patients was relatively poor. With regard to the need of elderly people, the usability and the layout, the different websites offer a lot of options for future improvements. CONCLUSION: Burn centers in Germany, Austria and Switzerland already consider the World Wide Web as an important tool for self-promotion and communication. The potential of burn center websites to function as a knowledge base for first aid as well as preventive measurements should be considered and realized in future web site designs. PMID- 22071362 TI - Distribution of oceanic 137Cs from the Fukushima Dai-ichi Nuclear Power Plant simulated numerically by a regional ocean model. AB - Radioactive materials were released to the environment from the Fukushima Dai ichi Nuclear Power Plant as a result of the reactor accident after the Tohoku earthquake and tsunami of 11 March 2011. The measured (137)Cs concentration in a seawater sample near the Fukushima Dai-ichi Nuclear Power Plant site reached 68 kBq L(-1) (6.8 * 10(4)Bq L(-1)) on 6 April. The two major likely pathways from the accident site to the ocean existed: direct release of high radioactive liquid wastes to the ocean and the deposition of airborne radioactivity to the ocean surface. By analysis of the (131)I/(137)Cs activity ratio, we determined that direct release from the site contributed more to the measured (137)Cs concentration than atmospheric deposition did. We then used a regional ocean model to simulate the (137)Cs concentrations resulting from the direct release to the ocean off Fukushima and found that from March 26 to the end of May the total amount of (137)Cs directly released was 3.5 +/- 0.7 PBq ((3.5 +/- 0.7) * 10(15)Bq). The simulated temporal change in (137)Cs concentrations near the Fukushima Daini Nuclear Power Plant site agreed well with observations. Our simulation results showed that (1) the released (137)Cs advected southward along the coast during the simulation period; (2) the eastward-flowing Kuroshio and its extension transported (137)C during May 2011; and (3) (137)Cs concentrations decreased to less than 10 BqL(-1) by the end of May 2011 in the whole simulation domain as a result of oceanic advection and diffusion. We compared the total amount and concentration of (137)Cs released from the Fukushima Dai-ichi reactors to the ocean with the (137)Cs released to the ocean by global fallout. Even though the measured (137)Cs concentration from the Fukushima accident was the highest recorded, the total released amount of (137)Cs was not very large. Therefore, the effect of (137)Cs released from the Fukushima Dai-ichi reactors on concentration in the whole North Pacific was smaller than that of past release events such as global fallout, and the amount of (137)Cs expected to reach other oceanic basins is negligible comparing with the past radioactive input. PMID- 22071364 TI - Men's experiences of gynaecomastia and corrective surgery: a qualitative report. PMID- 22071363 TI - Monitoring of aerosols in Tsukuba after Fukushima Nuclear Power Plant incident in 2011. AB - Artificial radionuclides were released into the atmosphere by the Fukushima Dai ichi Nuclear Power Plant incident after a strong earthquake on 11 March 2011. Aerosol monitoring at the Geological Survey of Japan, Tsukuba, was started 20 d after the incident. Radionuclides such as (99)Mo/(99m)Tc, (132)Te/(132)I, (129 m)Te/(129)Te, (131)I, (137)Cs, (136)Cs, (134)Cs, (140)Ba/(140)La, (110 m)Ag, and (95)Nb were observed and, with the exception of (137)Cs and (134)Cs, these radionuclides decreased to below the limit of detection in the middle of June. The activity ratio of atmospheric (134)Cs/(137)Cs in aerosols decreased over time almost following physical decays. Therefore, the (134)Cs/(137)Cs activity ratio in the averaged air mass in this study could be regarded as homogeneous although those of several reactors in the Nuclear Power Plant were not ascertained. A further research on the released (137)Cs and (134)Cs would be necessary for the sedimentology of lake sediment. PMID- 22071365 TI - Six-fold hexagonal symmetric nanostructures with various periodic shapes on GaAs substrates for efficient antireflection and hydrophobic properties. AB - We fabricated various periodic nanostructures with a six-fold hexagonal symmetry on gallium arsenide (GaAs) substrates using simple process steps, together with a theoretical analysis of their antireflective properties. Elliptical photoresist (PR) nanopillars, which are inevitably generated by the asymmetric intensity distribution of the laser interference, were converted to rounded lens-like patterns by a thermal reflow process without any additional complex optic systems, thus leading to an exact six-fold hexagonal symmetry. Various shaped periodic nanostructures including nanorods, cones, truncated cones, and even parabolic patterns were obtained under different etching conditions using the rounded lens-like PR patterns formed by the reflow process. For the parabolic structure, the calculated lowest average reflectance of ~ 2.3% was obtained. To achieve better antireflection characteristics, an aluminum-doped zinc oxide (AZO) film was deposited on the GaAs parabolas, which forms an AZO/GaAs parabolic nanostructure. The structure exhibited a low average reflectance of ~ 1.2% over a wide wavelength region of 350-1800 nm and a hydrophobic surface with a water contact angle of theta(c) ~ 115 degrees . The calculated reflectances were reasonably consistent with the measured results. PMID- 22071367 TI - The interruptive effect of pain in a multitask environment: an experimental investigation. AB - Daily life is characterized by the need to stop, start, repeat, and switch between multiple tasks. Here, we experimentally investigate the effects of pain, and its anticipation, in a multitask environment. Using a task-switching paradigm, participants repeated and switched between 3 tasks, of which 1 predicted the possible occurrence of pain. Half of the participants received low intensity pain (N = 30), and half high intensity pain (N = 30). Results showed that pain interferes with the performance of a simultaneous task, independent of the pain intensity. Furthermore, pain interferes with the performance on a subsequent task. These effects are stronger with high intensity pain than with low intensity pain. Finally, and of particular importance in this study, interference of pain on a subsequent task was larger when participants switched to another task than when participants repeated the same task. PERSPECTIVE: This article is concerned with the interruptive effect of pain on people's task performance by using an adapted task-switching paradigm. This adapted paradigm may offer unique possibilities to investigate how pain interferes with task performance while people repeat and switch between multiple tasks in a multitask environment. PMID- 22071366 TI - Individual differences in the effects of music engagement on responses to painful stimulation. AB - Engaged attention, including music listening, has shown mixed results when used as a method for reducing pain. Applying the framework of constructivism, we extend the concept of engagement beyond attention/distraction to include all cognitive and emotional/motivational processes that may be recruited in order to construct an alternative experience to pain and thus reduce pain. Using a music listening task varying in task demand, we collected stimulus-evoked potentials, pupil dilation, and skin conductance responses to noxious electrocutaneous stimulations as indicators of central and peripheral arousal, respectively. Trait anxiety (Spielberger State-Trait Anxiety Inventory) and absorption (Tellegen Absorption Scale) provided indicators of individual differences. One hundred and fifty-three healthy, normal volunteers participated in a test session in which they received 3 stimulus intensity levels while listening to background tones (No Task) or performing a music-listening task. Linear slopes indicating net engagement (change in stimulus arousal relative to task performance) decreased with increasing task demand and stimulus level for stimulus-evoked potentials. Slopes for pupil dilation response and skin conductance response varied with task demand, anxiety, and absorption, with the largest engagement effect occurring for high anxiety/high absorption participants. Music engagement reduces pain responses, but personality factors like anxiety and absorption modulate the magnitude of effect. PERSPECTIVE: Engaging in music listening can reduce responses to pain, depending on the person: people who are anxious and can become absorbed in activities easily may find music listening especially effective for relieving pain. Clinicians should consider patients' personality characteristics when recommending behavioral interventions like music listening for pain relief. PMID- 22071368 TI - On the role of thermal activation in selective photochemistry: mechanistic insight into the oxidation of propene on the V4O11- cluster. AB - An experimental methodology for a mechanistic analysis of gas phase chemical reactions is presented in the context of structure-reactivity relationships of metal oxide clusters relevant to photocatalysis. The spectroscopic approach is demonstrated with the investigation of the photoinduced oxygenation of propene on the V(4)O(11)(-) cluster, where the thermal activation and subsequent photoreaction are deduced with the information from (i) the temperature dependency of the aggregation kinetics in the propene-seeded helium atmosphere of an ion-trap reactor; (ii) the fluence dependency in the yield of different product channels of the photoreaction and (iii) the intensity dependency in the fragmentation of neutral reaction products that are probed via in situ multi photon ionization. For the thermal reaction, selective hydrogen abstraction from the allylic position of propene accompanied by the linkage to the cluster at the dioxo moiety is postulated as the mechanism in the aggregation of propene on the V(4)O(11)(-) cluster. In accordance with an insightful neutralization reionization study (Schroder et al., J. Mass. Spectrom., 2010, 301, 84), the subsequent photoinduced reaction is defined by an allylic oxidation in the formation of acrolein from the initial allyloxy radical photoproduct. The relevance of the observed selectivity is discussed in view of the electronic structure and bond motifs offered by high valence oxide systems such as the V(4)O(11)(-) cluster. PMID- 22071369 TI - Mercury levels and trends (1993-2009) in bream (Abramis brama L.) and zebra mussels (Dreissena polymorpha) from German surface waters. AB - Mercury concentrations have been analysed in bream (Abramis brama L.) and zebra mussels (Dreissena polymorpha) collected at 17 freshwater sites in Germany from 1993-2009 and 1994-2009, respectively, within the German Environmental Specimen programme. Mercury concentrations in bream ranged from 21 to 881 ng g(-1) wet weight with lowest concentrations found at the reference site Lake Belau and highest in fish from the river Elbe and its tributaries. Statistical analysis revealed site-specific differences and significant decreasing temporal trends in mercury concentrations at most of the sampling sites. The decrease in mercury levels in bream was most pronounced in fish from the river Elbe and its tributary Mulde, while in fish from the river Saale mercury levels increased. Temporal trends seem to level off in recent years. Mercury concentrations in zebra mussels were much lower than those in bream according to their lower trophic position and varied by one order of magnitude from 4.1 to 42 ng g(-1) wet weight (33-336 ng g( 1) dry weight). For zebra mussels, trend analyses were performed for seven sampling sites at the rivers Saar and Elbe of which three showed significant downward trends. There was a significant correlation of the geometric mean concentrations in bream and zebra mussel over the entire study period at each sampling site (Pearson's correlation coefficient=0.892, p=0.00002). A comparison of the concentrations in bream with the environmental quality standard (EQS) of 20 ng g(-1) wet weight set for mercury in biota by the EU showed that not a single result was in compliance with this limit value, not even those from the reference site. Current mercury levels in bream from German rivers exceed the EQS by a factor 4.5-20. Thus, piscivorous top predators are still at risk of secondary poisoning by mercury exposure via the food chain. It was suggested focusing monitoring of mercury in forage fish (trophic level 3 or 4) for compliance checking with the EQS for biota and considering the age dependency of mercury concentrations in fish in the monitoring strategy. PMID- 22071370 TI - Electrochemical oxidation of nitrogen-heterocyclic compounds at boron-doped diamond electrode. AB - Nitrogen-heterocyclic compounds (NHCs) are toxic and bio-refractory contaminants widely spread in environment. This study investigated electrochemical degradation of NHCs at boron-doped diamond (BDD) anode with particular attention to the effect of different number and position of nitrogen atoms in molecular structure. Five classical NHCs with similar structures including indole (ID), quinoline (QL), isoquinoline (IQL), benzotriazole (BT) and benzimidazole (BM) were selected as the target compounds. Results of bulk electrolysis showed that degradation of all NHCs was fit to a pseudo first-order equation. The five compounds were degraded with the following sequence: ID>QL>IQL>BT>BM in terms of their rates of oxidation. Quantum chemical calculation was combined with experimental results to describe the degradation character of NHCs at BDD anode. A linear relationship between degradation rate and delocalization energy was observed, which demonstrated that electronic charge was redistributed through the conjugation system and accumulated at the active sites under the attack of hydroxyl radicals produced at BDD anode. Moreover, atom charge was calculated by semi empirical PM3 method and active sites of NHCs were identified respectively. Analysis of intermediates by GC-MS showed agreement with calculation results. PMID- 22071371 TI - Genotoxicity assessment of water soluble fractions of biodiesel and its diesel blends using the Salmonella assay and the in vitro MicroFlow(r) kit (Litron) assay. AB - The designation of biodiesel as an environmental-friendly alternative to diesel oil has improved its commercialization and use. However, most biodiesel environmental safety studies refer to air pollution and so far there have been very few literature data about its impacts upon other biotic systems, e.g. water, and exposed organisms. Spill simulations in water were carried out with neat diesel and biodiesel and their blends aiming at assessing their genotoxic potentials should there be contaminations of water systems. The water soluble fractions (WSF) from the spill simulations were submitted to solid phase extraction with C-18 cartridge and the extracts obtained were evaluated carrying out genotoxic and mutagenic bioassays [the Salmonella assay and the in vitro MicroFlow(r) kit (Litron) assay]. Mutagenic and genotoxic effects were observed, respectively, in the Salmonella/microsome preincubation assay and the in vitro MN test carried out with the biodiesel WSF. This interesting result may be related to the presence of pollutants in biodiesel derived from the raw material source used in its production chain. The data showed that care while using biodiesel should be taken to avoid harmful effects on living organisms in cases of water pollution. PMID- 22071372 TI - Transcriptional effects of perfluorinated compounds in rat hepatoma cells. AB - Perfluorooctanesulfonate (PFOS) is the terminal degradation product of many commercially used perfluorinated compounds, and most of the toxicity testing to date has focused on its potential biological effects. While PFOS has been extensively studied, other PFCs including replacement chemicals such as perfluorobutanesulfonate (PFBS) and perfluorobutyric acid (PFBA), have not been well characterized. Despite the relative lack of data available on these other PFCs it has been assumed that they will cause similar or lesser effects than PFOS. This study compared the effects of 10 PFCs routinely found in the environment on mRNA abundance of 7 genes related to processes known to be affected by PFOS, such as fatty acid and cholesterol synthesis, and thyroid development. Rat H4IIE hepatoma cells were exposed and changes in mRNA abundance were quantified by real-time PCR. Significant changes in mRNA abundance were observed. The effects caused by the shorter chain replacement chemicals differed significantly from those caused by PFOS or PFOA. Furthermore, not all of the PFCs caused the same effects, and changes could not simply be attributed to chain length or functional group. These differences could mean that these replacement chemicals do not act through the same mechanisms as the more studied PFOS and PFOA. PMID- 22071373 TI - Henry's law constants of chlorinated solvents at elevated temperatures. AB - Henry's law constants for 12 chlorinated volatile organic compounds (CVOCs) were measured as a function of temperature ranging from 8 to 93 degrees C, using the modified equilibrium partitioning in closed system (EPICS) method. The chlorinated compounds include tetrachloroethylene, trichloroethylene, cis-1,2 dichloroethylene, vinyl chloride, 1,1,1-trichloroethane, 1,1-dichloroethane, 1,2 dichloroethane, chloroethane, carbon tetrachloride, chloroform, dichloromethane, and chloromethane. The variation in Henry's constants for these compounds as a function of temperature ranged from around 3-fold (chloroethane) to 30-fold (1,2 dichloroethane). Aqueous solubilities of the pure compounds were measured over the temperature range of 8-75 degrees C. The temperature dependence of Henry's constant was predicted using the ratio of pure vapor pressure to aqueous solubility, both of which are functions of temperature. The calculated Henry's constants are in a reasonable agreement with the measured results. With the improved data on Henry's law constants at high temperatures measured in this study, it will be possible to more accurately model subsurface remediation processes that operate near the boiling point of water. PMID- 22071374 TI - House crickets can accumulate polybrominated diphenyl ethers (PBDEs) directly from polyurethane foam common in consumer products. AB - Polybrominated diphenyl ether (PBDE) flame retardants are added at percent levels to many polymers and textiles abundant in human spaces and vehicles, wherein they have been long assumed to be tightly sequestered. However, the mgkg(-1) burdens recently detected in indoor dust testify to substantial releases. The bulk of released PBDEs remain in the terrestrial environment, yet comparatively little research focuses on this compartment. There, insects/arthropods, such as crickets, are the most abundant invertebrate organisms and facilitate the trophic transfer of contaminants by breaking down complex organic matter (including discarded polymers) and serving as food for other organisms. Our experiments revealed that house crickets (Acheta domesticus) provided uncontaminated food and free access to PUF containing Penta-BDE (8.7%drywt) for 28 d accumulated substantial PBDE body burdens. Crickets allowed to depurate gut contents exhibited whole body burdens of up to 13.4 mg kg(-1) lipid SigmaPenta-BDE, 1000 fold higher than typically reported in humans. Non-depurated crickets and molted exoskeletons incurred even higher SigmaPenta-BDE, up to 80.6 and 63.3 mg kg(-1) lipid, respectively. Congener patterns of whole crickets and molts resembled those of PUF and the commercial Penta-BDE formulation, DE-71, indicative of minimal discrimination or biotransformation. Accumulation factor (AF) calculations were hampered by uncertainties in determining actual PUF ingestion. However, estimated AFs were low, in the range of 10(-4)-10(-3), suggesting that polymer-PBDE interactions limited uptake. Nonetheless, results indicate that substantial PBDE burdens may be incurred by insects in contact with current-use and derelict treated polymers within human spaces and solid waste disposal sites (e.g. landfills, automotive dumps, etc.). Once ingested, even burdens not absorbed across the gut wall may be dispersed within proximate terrestrial food webs via the insect's movements and/or predation. PMID- 22071375 TI - Measurement of pyrene in the gills of exposed fish using synchronous fluorescence spectroscopy. AB - A synchronous fluorescence spectroscopy (SFS) method was developed for determination of pyrene in the gills of exposed fish. The wavelength differences (Deltalambda) of 50 nm was maintained between excitation and emission wavelengths and it was found to be suitable for the effective determination of pyrene in fish gills; the peak were observed at lambda(ex) 334.5 nm. Linear relationships between SFS intensity and the concentration of pyrene in n-hexane solution were established. It was demonstrated that the SFS method was effective, simple, and less expensive, providing an attractive alternative for the rapid analysis of pyrene in fish gills. PMID- 22071376 TI - Molecular-targeted nanotherapies in cancer: enabling treatment specificity. AB - Chemotherapy represents a mainstay and powerful adjuvant therapy in the treatment of cancer. The field has evolved from drugs possessing all-encompassing cell killing effects to those with highly targeted, specific mechanisms of action; a direct byproduct of enhanced understanding of tumorigenic processes. However, advances regarding development of agents that target key molecules and dysregulated pathways have had only modest impacts on patient survival. Several biological barriers preclude adequate delivery of drugs to tumors, and remain a formidable challenge to overcome in chemotherapy. Currently, the field of nanomedicine is enabling the delivery of chemotherapeutics, including repositioned drugs and siRNAs, by giving rise to carriers that provide for protection from degradation, prolonged circulation times, and increased tumor accumulation, all the while resulting in reduced patient morbidity. This review aims to highlight several innovative, nanoparticle-based platforms with the potential of providing clinical translation of several novel chemotherapeutic agents. We will also summarize work regarding the development of a multistage drug delivery strategy, a robust carrier platform designed to overcome several biological barriers while en route to tumors. PMID- 22071377 TI - Predictors of suicidal ideation with sub-optimal health status and anxiety symptom among Chinese adolescents. AB - Evidences in respect to the predictors of suicide ideation are uncertain and most associations only have been identified in cross-sectional studies. More information is needed to identify whether these predictors are true risk factors and can predict the development of suicidal ideation independently. Using the data from a prospective, longitudinal study (n = 2348), we examined the predictors of suicide ideation with demographic variety and psychological well being of adolescents. Positive items of sub-optimal health status and anxiety symptom at baseline could strongly predict the incidence of self-reported suicidal ideation on a 1-year follow-up study. These results have implications for programs aimed at identifying school students at risk for suicide. PMID- 22071378 TI - Association of the CHRNA5-A3-B4 gene cluster with heaviness of smoking: a meta analysis. AB - INTRODUCTION: Variation in the CHRNA5-A3-B4 gene cluster is a promising candidate region for smoking behavior and has been linked to multiple smoking-related phenotypes (e.g., nicotine dependence) and diseases (e.g., lung cancer). Two single nucleotide polymorphisms (SNPs), rs16969968 in CHRNA5 and rs1051730 in CHRNA3, have generated particular interest. METHODS: We evaluated the published evidence for association between rs16969968 (k = 27 samples) and rs1051730 (k = 44 samples) SNPs with heaviness of smoking using meta-analytic techniques. We explored which SNP provided a stronger genetic signal and investigated study level characteristics (i.e., ancestry, disease state) to establish whether the strength of association differed across populations. We additionally tested for small study bias and explored the impact of year of publication. RESULTS AND CONCLUSIONS: Meta-analysis indicated compelling evidence of an association between the rs1051730/rs16966968 variants and daily cigarette consumption (fixed effects: B = 0.91, 95% CI = 0.77, 1.06, p < .001; random effects: B = 1.01, 95% CI = 0.81, 1.22, p < .001), equivalent to a per-allele effect of approximately 1 cigarette/day. SNP rs1051730 was found to provide a stronger signal than rs16966968 in stratified analyses (p(diff) = .028), although this difference was only qualitatively observed in the subset of samples that provided data on both SNPs. While the functional relevance of rs1051730 is unknown, it may be a strong tagging SNP for functional haplotypes in this region. PMID- 22071380 TI - Long-term follow-up of DDD and VDD pacing: a prospective non-randomized single centre comparison of patients with symptomatic atrioventricular block. AB - AIMS: This prospective non-randomized single-centre registry compared clinical outcome, pacing parameters, and long-term survival in patients receiving VDD or DDD pacemaker (PMs) for symptomatic atrioventricular (AV) block. METHODS AND RESULTS: Single-lead VDD (n= 166) and DDD (n= 254) PMs were implanted in 420 successive patients with isolated AV block between January 2001 and December 2009. At the end of the follow-up period [median 25 (1-141) months], there was no difference in the incidence of atrial fibrillation [11.2% in the VDD group; 11.4% in the DDD group (P= 0.95)], myocardial infarction [31.1% in the VDD group; 25.2% in the DDD group (P= 0.20)], or dilated cardiomyopathy [9.9% in the VDD group; 8.9% in the DDD group (P= 0.74)]. At last follow-up, 65.9% of the VDD PMs and 89.3% of the DDD PMs were still programmed in their original mode with good atrial sensing. Due to permanent atrial fibrillation, 7.9% patients out of the VDD group had been switched to VVIR mode and 8.7% patients out of the DDD group to VVIR or DDIR mode. The P-wave amplitude was poor (sensed P-wave <0.5 mV) in 19.1% of the VDD PM and 1.6% of the DDD PM (P< 0.001) and 7.1% of the VDD patients and 0.4% of the DDD patients had been switched to VVIR pacing mode due to P-wave undersensing and AV dissociation (P= 0.003). Symptomatic atrial undersensing requiring upgrading was similar in both groups. The overall survival, adjusted for age, was not significantly different in the VDD and the DDD group (log rank: 0.26). Moreover, Cox survival analysis excluded the pacing mode as a significant predictor of mortality [hazard ratio (HR) = 0.79, confidence interval (CI) (0.46-1.35), P= 0.39]. CONCLUSION: Comparing VDD and DDD pacing, a significantly larger number of VDD-paced patients developed poor atrial signal detection without clinical impact. However, atrial under sensing did not influence the incidence of atrial fibrillation, myocardial infarction, dilated cardiomyopathy, or mortality. PMID- 22071381 TI - Unusual failure of left ventricular lead implantation diagnosed by multidetector computed tomography. PMID- 22071382 TI - Women and minorities are less likely to receive an implantable cardioverter defibrillator for primary prevention of sudden cardiac death. AB - INTRODUCTION: Implantable cardioverter defibrillators (ICDs) improve survival in patients with depressed left ventricular ejection fraction (EF). We investigated whether women and minorities are as likely as white men to receive an ICD for primary prevention of sudden cardiac death. METHODS AND RESULTS: We reviewed the electronic medical records of patients with cardiomyopathy by nuclear single photon emission computed tomography imaging (EF <= 35%), who had no prior history of sustained ventricular arrhythmias. Clinical and demographic data were collected and the Charlson comorbidity index (CCI) was calculated for each patient. A total of 233 non-selected patients (age = 68 +/- 12 years, 29% women, 21% black, EF 24 +/- 6%, CCI 6.62 +/- 2.9) were included in this analysis of whom 111 (48%) received an ICD. In univariate analysis, ICD recipients were more likely to be Caucasian men compared with black men or women from all races. After adjusting for race, gender, EF, and the CCI in a multivariate logistic regression model, women were 61% less likely than men [odds ratio (OR) = 0.39, 95% confidence interval (CI) 0.20-0.74, P= 0.004] and blacks were 72% less likely than whites (OR = 0.28, 95% CI 0.13-0.59, P= 0.001) to receive an ICD. CONCLUSIONS: Even after adjusting for comorbid conditions, gender, and racial discrepancies in the implantation of ICDs for the primary prevention of sudden cardiac death exist. Further investigations into the root causes of these discrepancies are needed before any corrective measures can be adopted. PMID- 22071383 TI - Implantable loop recorders are cost-effective when used to investigate transient loss of consciousness which is either suspected to be arrhythmic or remains unexplained. AB - AIMS: To assess the cost-effectiveness of implantable loop recorders (ILRs) in people with transient loss of consciousness (TLoC), which, after initial assessment and specialist cardiovascular assessment, is either suspected to be arrhythmic in origin or remains unexplained. This analysis was conducted to inform clinical guideline recommendations made by the National Institute for Health and Clinical Excellence (NICE) on the management of TLoC. METHODS AND RESULTS: Decision analytic modelling was used to estimate the costs and benefits of using ILRs compared with a strategy of no further diagnostic testing. Diagnostic outcomes were estimated from a systematic review and used to populate a decision tree model. To capture the main consequences of diagnosis, the costs and benefits of treatment for several clinically significant arrhythmias were estimated within the model. We used a cost-utility approach, in which benefits are measured using quality adjusted life years (QALYs), and took a UK National Health Service (NHS) and personal social services perspective. The cost per QALY was L17,400 in patients with unexplained syncope and L16,400 in patients with suspected arrhythmic syncope. Sensitivity analysis found that the cost effectiveness estimates are fairly robust despite the areas of uncertainty identified in the evidence and assumptions used to inform the model. CONCLUSIONS: Implantable loop recorder monitoring is likely to be a cost-effective strategy in people presenting to the UK NHS who are experiencing infrequent episodes of TLoC which either remain unexplained or are suspected to be arrhythmic after initial assessment and specialist cardiovascular assessment. Implantable loop recorder monitoring has been recommended by NICE for these populations. PMID- 22071384 TI - The influence of bacille Calmette-Guerin vaccine strain on the immune response against tuberculosis: a randomized trial. AB - RATIONALE: Approximately 100 million doses of bacille Calmette-Guerin (BCG) vaccine are given each year to protect against tuberculosis (TB). More than 20 genetically distinct BCG vaccine strains are in use worldwide. Previous studies suggest that BCG vaccine strain influences the immune response and protection against TB. Current data on which BCG vaccine strain induces the optimal immune response in humans are insufficient. OBJECTIVES: To compare the immune response to three different BCG vaccine strains given to infants at birth. METHODS: Newborn infants in a tertiary women's hospital were immunized at birth with one of three BCG vaccine strains. A stratified randomization according to the mother's region of birth was used. MEASUREMENTS AND MAIN RESULTS: The presence of mycobacterial-specific polyfunctional CD4 T cells measured by flow cytometry 10 weeks after immunization. Of the 209 infants immunized, data from 164 infants were included in the final analysis (BCG-Denmark, n = 54; BCG-Japan, n = 54; BCG Russia, n = 57). The proportion of polyfunctional CD4 T cells was significantly higher in infants immunized with BCG-Denmark (0.013%) or BCG-Japan (0.016%) than with BCG-Russia (0.007%) (P = 0.018 and P = 0.003, respectively). Infants immunized with BCG-Japan had higher concentrations of secreted Th1 cytokines; infants immunized with BCG-Denmark had higher proportions of CD107-expressing cytotoxic CD4 T cells. CONCLUSIONS: There are significant differences in the immune response induced by different BCG vaccine strains in newborn infants. Immunization with BCG-Denmark or BCG-Japan induced higher frequencies of mycobacterial-specific polyfunctional and cytotoxic T cells and higher concentrations of Th1 cytokines. These findings have potentially important implications for global antituberculosis immunization policies and future tuberculosis vaccine trials. PMID- 22071386 TI - Empyema necessitatis due to Actinomyces israelii. PMID- 22071385 TI - A mediation model linking body weight, cognition, and sleep-disordered breathing. AB - RATIONALE: Academic success involves the ability to use cognitive skills in a school environment. Poor academic performance has been linked to disrupted sleep associated with sleep-disordered breathing (SDB). In parallel, poor sleep is associated with increased risk for obesity, and weight management problems have been linked to executive dysfunction, suggesting that interactions may be operational between SDB and obesity to adversely affect neurocognitive outcomes. OBJECTIVES: To test whether mediator relationships exist between body weight, SDB, and cognition. METHODS: Structural equation modeling was conducted on data from 351 children in a community-based cohort assessed with the core subtests of the Differential Abilities Scales after an overnight polysomnogram. Body mass index, apnea-hypopnea index, and cognitive abilities were modeled as latent constructs. MEASUREMENTS AND MAIN RESULTS: In a sample of predominantly white children 6 to 10 years of age, SDB amplified the adverse cognitive and weight outcomes by 0.55- to 0.46-fold, respectively. Weight amplified the risk by 0.39- to 0.40-fold for SDB and cognitive outcomes, respectively. Poor ability to perform complex mental processing functions increased the risk of adverse weight and SDB outcomes by 2.9- and 7.9-fold, respectively. CONCLUSIONS: Cognitive functioning in children is adversely affected by frequent health-related problems, such as obesity and SDB. Furthermore, poorer integrative mental processing may place a child at a bigger risk for adverse health outcomes. PMID- 22071387 TI - ACSM Clinician Profile. PMID- 22071388 TI - Placebos, expectations, and the power of words. PMID- 22071390 TI - Sport physicians should practice the full gamut of their profession: moving from sports medicine to sports and exercise medicine. PMID- 22071391 TI - Sideline acupuncture for acute pain control: a case series. PMID- 22071392 TI - Head injuries, heading, and the use of headgear in soccer. AB - Soccer has more than 265 million players around the world and is the only contact sport with purposeful use of the head for controlling and advancing the ball. Head contact in soccer has the potential to cause acute traumatic brain injury including concussion or, potentially, a pattern of chronic brain injury. Although early retrospective research on the effects of soccer heading seemed to suggest that purposeful heading may contribute to long-term cognitive impairment, prospective controlled studies do not support this and, in fact, suggest that purposeful heading may not be a risk factor for cognitive impairment. Headgear has not been shown to be effective in reducing ball impact but may be helpful in reducing the force of non-ball-related impacts to the head. There are concerns that universal use of headgear may cause more aggressive heading and head challenges, leading to increased risk of injury. PMID- 22071393 TI - Nutrition update for the ultraendurance athlete. AB - Participation in ultraendurance events has been increasing. Appropriate nutrition in training and fueling while racing within the confines of gastrointestinal tolerability is essential for optimal performance. Unfortunately, there has been a paucity of studies looking at this special population of athletes. Recent field studies have helped to clarify appropriate fluid intake and dispel the myth that moderate dehydration while racing is detrimental. Additional current nutrition research has looked at the role of carbohydrate manipulation during training and its effect on macronutrient metabolism, as well as of the benefits of the coingestion of multiple types of carbohydrates for race fueling. The use of caffeine and sodium ingestion while racing is common with ultraendurance athletes, but more research is needed on their effect on performance. This article will provide the clinician and the athlete with the latest nutritional information for the ultraendurance athlete. PMID- 22071394 TI - Snowboarding injuries. AB - Snowboarding has gained immense popularity during the past 30 years and continues to appeal to many young participants. Injury patterns and characteristics of injuries seen commonly in snowboarders have rapidly evolved during this time. Risk factors have emerged, and various methods of reducing injuries to snowboarders have been investigated. It is important that medical providers are knowledgeable about this growing sport and are prepared to adequately evaluate and treat snowboarding injuries. This article will review the issues and discuss diagnostic and treatment principles regarding injuries seen commonly in snowboarders. Injury prevention should be emphasized, particularly with young riders and beginners. PMID- 22071395 TI - Review and role of plyometrics and core rehabilitation in competitive sport. AB - Core stability and plyometric training have become common elements of training programs in competitive athletes. Core stability allows stabilization of the spine and trunk of the body in order to allow maximal translation of force to the extremities. Plyometric training is more dynamic and involves explosive-strength training. Integration of these exercises theoretically begins with core stabilization using more static exercises, allowing safe and effective transition to plyometric exercises. Both core strengthening and plyometric training have demonstrated mixed but generally positive results on injury prevention rehabilitation of certain types of injuries. Improvement in performance compared to other types of exercise is unclear at this time. This article discusses the theory and strategy behind core stability and plyometric training; reviews the literature on injury prevention, rehabilitation of injury, and performance enhancement with these modalities; and discusses the evaluation and rehabilitation of core stability. PMID- 22071396 TI - Physical activity prescription for childhood cancer survivors. AB - Physical activity can play a vital role in the treatment and prevention of many of the long-term effects of childhood cancer and cancer therapy. Specifically, physical activity may attenuate the long-term risk for adverse cardiovascular effects, low bone density, obesity, and poor quality-of-life measures. Physicians caring for long-term survivors of cancer should be prepared to evaluate the survivor's risk for long-term effects and provide accurate advice regarding the prescription of physical activity for the management and prevention of these problems. Knowing when physical activity prescription can help mitigate the late effects of childhood cancer and cancer therapy, and the barriers to physical activity for survivors, will help physicians provide quality care to childhood cancer survivors. PMID- 22071397 TI - Do youth sports prevent pediatric obesity? A systematic review and commentary. AB - Sport is a promising setting for obesity prevention among youth, but little is known about whether it prevents obesity. We reviewed research comparing sport participants with nonparticipants on weight status, physical activity, and diet. Among 19 studies, we found no clear pattern of association between body weight and sport participation. Among 17 studies, we found that sport participants are more physically active than those who do not participate. We found seven studies that compared the diet of sport participants with non-participants. These studies reported that youth involved in sport were more likely to consume fruits, vegetables, and milk, and also more likely to eat fast food and drink sugar sweetened beverages and consume more calories overall. It is unclear from these results whether sports programs, as currently offered, protect youth from becoming overweight or obese. Additional research may foster understanding about how sport, and youth sport settings, can help promote energy balance and healthy body weight. PMID- 22071398 TI - Posterior ankle impingement in the dancer. AB - Dancers spend a lot of time in the releve position in demi-pointe and en pointe in their training and their careers. Pain from both osseous and soft tissue causes may start to occur in the posterior aspect of their ankle. This article reviews the potential causes of posterior ankle impingement in dancers. It will discuss the clinical evaluation of a dancer and the appropriate workup and radiographic studies needed to further evaluate a dancer with suspected posterior ankle impingement. PMID- 22071399 TI - Cardiovascular risk factors in football players. AB - Cardiovascular disease is a leading cause of death in the United States. Football players represent a subpopulation that may have a unique risk profile pattern. Studies have suggested that football players may be at increased risk for cardiovascular disease. Paradoxically, there may be a cardioprotective effect associated with activity in general and, specifically, participation at higher levels of football. Our review will attempt to outline the pertinent evidence in regards to cardiovascular risk factors in football players. Specifically, hypertension, hypercholesterolemia, obesity, and sedentary lifestyle will be considered. In addition, we will discuss potential risk factors for investigation including C-reactive protein, homocysteine, insulin resistance, and sleep disordered breathing. Studies at all levels of competition will be considered, including retired players whose findings may represent lifelong changes that occur as a result of participation in football. Further investigation will be needed to help clarify the relationship between football participation and cardiovascular risk. PMID- 22071400 TI - Consortium for Health and Military Performance and American College of Sports Medicine consensus paper on extreme conditioning programs in military personnel. AB - A potential emerging problem associated with increasingly popularized extreme conditioning programs (ECPs) has been identified by the military and civilian communities. That is, there is an apparent disproportionate musculoskeletal injury risk from these demanding programs, particularly for novice participants, resulting in lost duty time, medical treatment, and extensive rehabilitation. This is a significant and costly concern for the military with regard to effectively maintaining operational readiness of the Force. While there are certain recognized positive aspects of ECPs that address a perceived and/or actual unfulfilled conditioning need for many individuals and military units, these programs have limitations and should be considered carefully. Moreover, certain distinctive characteristics of ECPs appear to violate recognized accepted standards for safely and appropriately developing muscular fitness and are not uniformly aligned with established and accepted training doctrine. Accordingly, practical solutions to improve ECP prescription and implementation and reduce injury risk are of paramount importance. PMID- 22071401 TI - Glycogen replenishment with chocolate milk consumption. PMID- 22071402 TI - Response to the article on baseline neuropsychological testing: throwing away clinical gold with the statistical bathwater. PMID- 22071408 TI - Muscle strength and soccer practice as major determinants of bone mineral density in adolescents. AB - OBJECTIVES: To analyse the relationship between isokinetic strength of the lower limb muscles and bone mineral density and content (BMD, BMC) of adolescent male soccer players and age-matched controls not involved in sport (12-15 years). METHODS: A random sample of 151 young males was divided into soccer players (SG; n=117) and control subjects (CG; n=34). Peak torque of knee extensors (PTE) and flexors (PTF) was measured during isokinetic knee joint movement (90 degrees /s) of the dominant and non-dominant lower limbs. BMD and BMC of the whole-body, lumbar spine, dominant/non-dominant lower limb were determined by dual-energy X ray absorptiometry. Physical activity was monitored with accelerometers during 5 days. Estimated maturity offset was used as an indicator of biological maturity status. RESULTS: Whole-body BMD (1.03+/-0.01 vs. 0.98+/-0.01 g/cm2, P=0.003) and dominant (1.09+/-0.01 vs. 1.02+/-0.01 g/cm2, P<0.001) and non-dominant (1.09+/ 0.01 vs. 1.01+/-0.01 g/cm2, P<0.001) lower limb BMD was greater in SG compared to CG. No significant differences were found for BMC. Compared to CG, SG performed better in the YY-IE2 test (780+/-40 vs. 625+/-31 m), exhibited higher PTE (dominant limb: 155.2+/-30.3 vs. 123.4+/-37.0N m; non-dominant limb: 156.2+/-36.1 vs. 120.4+/-41.1 N m) and PTF muscles (dominant limb: 79.0+/-25.3 vs. 57.1+/-25.3 Nm; non-dominant limb: 73.3+/-20.7 vs. 57.0+/-24.2N m). Moreover, the PTE, soccer participation and maturity status were positively associated with the BMD at all body sites (r2=0.57-0.73, P<0.05). CONCLUSIONS: Muscle strength of knee extensors is associated with BMD and BMC at all body sites. Muscle-skeletal structures respond positively to the weight-bearing and impact-loading imposed by soccer practice. Soccer seemed to be a multilateral balanced sport activity. PMID- 22071409 TI - An analysis of the pharmacokinetic parameter ratios in DCE-MRI using the reference region model. AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is performed by obtaining sequential MRI images, before, during and after the injection of a contrast agent. It is usually used to observe the exchange of contrast agent between the vascular space and extravascular extracellular space (EES), and provide information about blood volume and microvascular permeability. To estimate the kinetic parameters derived from the pharmacokinetic model, accurate knowledge of the arterial input function (AIF) is very important. However, the AIF is usually unknown, and it remains very difficult to obtain such information noninvasively. In this article, without knowledge of the AIF, we applied a reference region (RR) model to analyze the kinetic parameters. The RR model usually depends on kinetic parameters found in previous studies of a reference region. However, both the assignment of reference region parameters (intersubject variation) and the selection of the reference region itself (intrasubject variation) may confound the results obtained by RR methods. Instead of using literature values for those pharmacokinetic parameters of the reference region, we proposed to use two pharmacokinetic parameter ratios between the tissue of interest (TOI) and the reference region. Specifically, one parameter K(R) is calculated as the ratio between the volume transfer constant K(trans) of the TOI and RR. Similarly, another parameter V(R) is calculated as the ratio between the extravascular extracellular volume fraction v(e) of the TOI and RR. To investigate the consistency of the two ratios, the K(trans) of the RR was varied ranging from 0.1 to 1.0 min(-1), covering the cited literature values. A simulated dataset with different levels of Gaussian noises and an in vivo dataset acquired from five canine brains with spontaneous occurring brain tumors were used to study the proposed ratios. It is shown from both datasets that these ratios are independent of K(trans) of the RR, implying that there is potentially no need to obtain information about literature values from the reference region for future pharmacokinetic modeling and analysis. PMID- 22071410 TI - Automatic segmentation of brain white matter and white matter lesions in normal aging: comparison of five multispectral techniques. AB - White matter loss, ventricular enlargement and white matter lesions are common findings on brain scans of older subjects. Accurate assessment of these different features is therefore essential for normal aging research. Recently, we developed a novel unsupervised classification method, named 'Multispectral Coloring Modulation and Variance Identification' (MCMxxxVI), that fuses two different structural magnetic resonance imaging (MRI) sequences in red/green color space and uses Minimum Variance Quantization (MVQ) as the clustering technique to segment different tissue types. Here we investigate how this method performs compared with several commonly used supervised image classifiers in segmenting normal-appearing white matter, white matter lesions and cerebrospinal fluid in the brains of 20 older subjects with a wide range of white matter lesion load and brain atrophy. The three tissue classes were segmented from T(1)-, T(2)-, T(2)*- and fluid attenuation inversion recovery (FLAIR)-weighted structural MRI data using MCMxxxVI and the four supervised multispectral classifiers available in the Analyze package, namely, Back-Propagated Neural Networks, Gaussian classifier, Nearest Neighbor and Parzen Windows. Bland-Altman analysis and Jaccard index values indicated that, in general, MCMxxxVI performed better than the supervised multispectral classifiers in identifying the three tissue classes, although final manual editing was still required to deliver radiologically acceptable results. These analyses show that MVQ, as implemented in MCMxxxVI, has the potential to provide quick and accurate white matter segmentations in the aging brain, although further methodological developments are still required to automate fully this technique. PMID- 22071411 TI - Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis. AB - OBJECTIVE: The development of osteoarthritis following traumatic anterior cruciate ligament (ACL) injury is well established. However, few reliable indicators of early osteoarthritic changes have been established, which has limited the development of effective therapies. T(1rho) and T(2) mapping techniques have the ability to provide highly accurate and quantitative measurements of articular cartilage degeneration in vivo. Relating these cartilaginous changes to high-resolution bone-densitometric evaluations of the late-stage osteoarthritic bone is crucial in elucidating the mechanisms of development of traumatic osteoarthritis (OA) and potential therapies for early- or late-stage intervention. METHODS: Twelve rabbits were monitored with in vivo magnetic resonance imaging (MRI) scans following ACL transection surgery with a contralateral leg sham operation. Six of the rabbits were treated with oral doxycycline for the duration of the experiment. At 12 weeks, the excised knees from three animals from each group (n=6 overall) were subjected to micro-computed tomography (CT) analysis. RESULTS: Consistent with previous studies, initial elevations in T(1rho) and T(2) values in ACL-transected animals were observed with relative normalization towards values see in sham-operated legs over the 12 week study. This biphasic pattern could hold diagnostic potential to differentiate osteoarthritic cartilage by tracking the relative proportions of T(1rho) and T(2) values as they rise with inflammation then fall as collagen and proteoglycan loss leads to further dehydration. The addition of doxycycline resulted in inconclusive, yet potentially interesting, cartilaginous changes in several compartments of the rabbit legs. Micro-CT studies demonstrated decreased bone densitometrics in ACL-transected knees. Correlation studies suggest that the cartilaginous changes may be associated with some aspects of bony change and the development of OA. CONCLUSION: We conclude that there are definite relationships between cartilaginous changes as seen on MRI and late-stage microstructural bony changes after traumatic ACL injury in rabbits. In addition, doxycycline may show promise in mitigating early-stage cartilage damage that may serve to lessen late stage osteoarthritic changes. This study demonstrates the ability to track OA progression and therapeutic efficacy with imaging modalities in vivo. PMID- 22071412 TI - Quantitative measurement of radial head fracture location. AB - BACKGROUND: The most common location of a displaced fracture of part of the radial head is often described as the anterior lateral aspect of the radial head with the forearm in neutral position, based on observation rather than precise measurements. The purpose of our study was to measure the exact location of fractures involving part of the radial head using quantitative 3-dimensional computed tomography (CT). MATERIALS AND METHODS: We measured the fracture lines with respect to the biceps tuberosity in 24 patients with a displaced articular fracture of part of the radial head (Mason type 2). Two observers preformed each measurement twice. Reliability was measured using the concordance correlation coefficient according to Lin. RESULTS: The average start of the fracture was 97 degrees (standard deviation [SD]) 48.3 degrees ; range 31 degrees -254 degrees ) clockwise from the biceps tuberosity, the average end of the fracture was 241.6 degrees (SD, 61.0; range 19 degrees -330 degrees ), and the average fracture subtends was 170 degrees (SD, 32.8 degrees ; range 99 degrees -252 degrees ). The fracture was through the anterolateral quadrant of the radial head in 22 of the 24 patients and through the posteromedial quadrant in 2 patients. CONCLUSION: This quantitative analysis of CT scans of displaced articular fractures of part of the radial head (Mason type 2) confirms that the most common location is the anterolateral quadrant with the forearm in neutral rotation. Given the important role of the radial head in elbow stability, more accurate characterization of incomplete radial head fractures may improve our understanding of treatment and outcome of these fractures. PMID- 22071413 TI - Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women. AB - Visceral fat accumulation has an important role in increasing the morbidity and mortality rates, by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that are associated with increased systolic and diastolic blood pressures have been identified by genome-wide association studies in Caucasian populations. This study investigates whether single nucleotide polymorphisms (SNPs) that confer susceptibility to high blood pressure are also associated with visceral fat obesity. We genotyped 1279 Japanese subjects (556 men and 723 women) who underwent computed tomography for measuring the visceral fat area (VFA) and subcutaneous fat area (SFA) at the following SNPs: FGF5 rs16998073, CACNB2 rs11014166, C10orf107 rs1530440, CYP17A1 rs1004467, NT5C2 rs11191548, PLEKHA7 rs381815, ATP2B1 rs2681472 and rs2681492, ARID3B rs6495112, CSK rs1378942, PLCD3 rs12946454, and ZNF652 rs16948048. In an additive model, risk alleles of the CYP17A1 rs1004467 and NT5C2 rs11191548 were found to be significantly associated with reduced SFA (P=0.00011 and 0.0016, respectively). When the analysis was performed separately in men and women, significant associations of rs1004467 (additive model) and rs11191548 (recessive model) with reduced VFA (P=0.0018 and 0.0022, respectively) and SFA (P=0.00039 and 0.00059, respectively) were observed in women, but not in men. Our results suggest that polymorphisms in the CYP17A1 and NT5C2 genes influence a reduction in both visceral and subcutaneous fat mass in Japanese women. PMID- 22071414 TI - In vitro evaluation of cytotoxicity of permanent prosthetic materials. AB - OBJECTIVES: To assess qualitative and quantitative cytotoxicity effect on permanent prosthetic materials to human gingival fibroblasts. METHODS: Human gingival tissues were collected (with informed consent) from patients undergoing periodontal surgical procedures and fibroblasts were cultured in vitro. Cell type was determined by performing proteomic analysis. Selected prosthetic materials including titanium, feldspathic ceramic, gold and chrome-cobalt alloy specimens (5*2 mm) were fabricated. The toxicity of prepared specimens was tested by exposing them to cell culture medium for 48, 72, 96 and 120 hours at 37 degrees C under sterile conditions. Cell viability was estimated using MTT (3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. The data concerning cell viability were statistically analyzed using two-way ANOVA test and Tukey multiple comparison test. RESULTS: Results obtained after 48 hours showed no toxic effect of titanium compared to control group. Cytotoxic effect was observed in gold alloy and feldspathic ceramic, however, it was not significant compared to control group. Chrome-cobalt alloy significantly reduced cell viability compared to control group (p<=0.001). Cytotoxicity diminished with increasing incubation time of specimens. After 120 hours of incubation all tested materials, except chrome-cobalt alloy, had no cytotoxicity. CONCLUSIONS: Titanium proved to be non-toxic. Gold alloy and feldspathic ceramic had short-term cytotoxic effect. Chrome-cobalt alloy had highest cytotoxic effect on fibroblast cells. PMID- 22071415 TI - Specific signaling molecule expressions in the interradicular septum in different age groups. AB - INTRODUCTION: Orthodontic teeth movement is accompanied by the remodeling of alveolar bone, including the interradicular septum. Bone contains three cell types, osteoblasts, osteocytes, and osteoclasts that are in direct contact with all of the cellular elements in the bone marrow. Marrow is the source of both bone-building osteoblasts and bone destroying osteoclasts, and the turnover of bone occurs throughout life. Bone signalling molecules have important functions during osteogenesis, and they are active in the bone remodelling process. Patients involved in orthodontic treatment belong to different age groups: therefore age must be considered as a contributing factor compromising the osteogenetic potential of bone. The aim of the current study was to investigate the specific expression of signalling molecules in the interradicular septum in different age groups. MATERIALS AND METHODS: The study group included 17 patients to whom the extraction of teeth was recommended as part of further orthodontic treatment. Patients (9 males and 8 females) - were divided into 3 groups 1st group - 12-14 years old); 2nd group - 15-22 years old; 3rd group - 23 years old or older. Expression of BMP 2/4, TGF-alpha, IL-1, IL-8, OPG, MMP-1, MMP-2, MMP-8, MMP-9, MMP-13, NGFR, NKpB 105, osteocalcin, and osteopontin in interradicular septum tissues was examined. TUNEL staining was also completed. The distribution of these factors was evaluated semi quantitalively. RESULTS: In the interradicular septum bone structure, the expression levels of osteocalcin, osteoprotegerin, matrix metalloproteinases 8 and 9, and nuclear factor kappa B were determined in all samples. TUNEL staining was also done. Age related decreases in the mean values of signalling factors and the number of apoptotic cells were statistically significant. CONCLUSION: Specific to interradicular septum osteoblasts and osteoclasts factors include osteoprotegerin, osteocalcin, matrix metalloproteinase 8, matrix metallproteniase 9, and nuclear factors kappa B. The mean expression levels of these proteins and the mean TUNEL staining statistically significantly decreased with age. This is preliminary study and more patients are necessary for more precise statistical analysis in the future. PMID- 22071416 TI - Soft tissue thickness changes after correcting Class III malocclusion with bimaxillar surgery. AB - THE AIM OF THIS STUDY was to evaluate and analyse soft tissue thickness changes after bimaxillary orthognathic surgery. MATERIALS AND METHODS: Eighty three consecutive patients (54 males and 29 females) with Class III malocclusion operated with bimaxillary orthognathic surgery were enrolled in this study. Standardized lateral cephalograms of adequate quality were analysed. RESULTS: The mean upper lip thickness decreased as a result of the surgery and statistically significant differences were recorded (p<0.01). The statistically significant difference in the post surgical tissue thickness of the lower lip also was recorded (p<0.05). Subjects with thick upper lips compared to patients with thin upper lips demonstrated greater (0.7 mm) and statistically significant (p<0.01) increase of vertical nasal projection. Vertical growth pattern had an influence only on B point to lower lip distance, which exhibited greater (2.2 mm; p<0.01) decrease during observation period. CONCLUSION: It was found differences in the soft tissue responses between patients with thick or thin soft tissues after bimaxillary surgery and it should be taken into account while planning operation. PMID- 22071417 TI - Postmenopausal osteoporosis and tooth loss. AB - OBJECTIVE: The aim of this study was to determine relation between tooth loss and general body bone mineral density in postmenopausal female who were seeking for prosthetic treatment. MATERIAL AND METHODS: There were included 79 women in this study (age from 49-81 years, mean age 62.9 years) with partial tooth loss. For all patients bone mineral density measurements for lumbar spine and both femoral necks by dual energy X-ray absorptiometry (Lunar DEXA DPX-NT, GE Medical Systems) were performed. Based on DEXA results patients were divided into 3 groups: normal bone density (T-score >=-1.0), osteopenia (T-score from -1.0 till -2.5) and osteoporosis (T-score <=-2.5). Dental investigation was performed to detect existing teeth. ANOVA analysis of variance was used to determine relationship between different variables by group. To test correlation between different values Pearson correlation was used. RESULTS: The number of teeth in different bone mineral density groups is almost similar. There are no statistically significant differences between groups according the number of the all teeth present and according the number of teeth in maxilla and mandible. There is no significant correlation between the number of the teeth and DEXA readings, except there is weak correlation between the number of maxillary posterior teeth and bone mineral density in femoral neck. CONCLUSION: There is no correlation between number of the teeth and general bone mineral density. PMID- 22071418 TI - Growth factors, genes, bone proteins and apoptosis in the temporomandibular joint (TMJ) of children with ankylosis and during disease recurrence. AB - AIM OF STUDY was complex detection of appearance and distribution of growth factors, facial bone growth stimulating genes, ground substance proteins and apoptosis in bone of ankylotic TMJ in primary and repeatedly operated children. MATERIALS AND METHODS: Ankylotic tissue was obtained during the arthroplastic surgery from two 6 years old children (boy and girl) with osseous type of disease. The girl underwent the repeated surgery in TMJ due to the same diagnosis in age of 12 years. Ankylotic tissue was proceeded for detection of BMP2/4, TGFbeta, Msx2, osteopontin, osteocalcin immunohistochemically, and apoptosis. RESULTS demonstrated massive bone formation intermixed by neochondrogenesis the lack of BMP 2/4, but abundant number of TGFbeta-containing cells in bone of all tested cases. Despite rich osteopontin positive structures in bone obtained from both - primary and repeated surgery, osteocalcin demonstrated variable appearance in 6 years aged children, but was abundant in joint 5 years later during disease recurrence. Expression of Msx2 varied widely before, but with tendency to decrease stabilized until few positive cells in bone of 12 years old girl. Apoptosis practically was not detected in primarily operated TMJ, but massively affected the supportive tissue in girl with recurrent ankylosis. CONCLUSIONS: The lack of BMP2/4 expression in ankylotic bone proves the disorders in cellular differentiation with simultaneous compensatory intensification of cellular proliferation and/or growth by rich expression of TGFbeta leading to the remodelling of TMJ. Mainly rich distribution of osteocalcin and osteopontin indicate the intensive mineralization processes of ankylotic bone. Persistent Msx2 expression is characteristic for the supportive tissue of recurrent ankylosis of TMJ and indicates the persistent stimulation of bone growth compensatory limitated by massive increase of programmed cell death. PMID- 22071419 TI - Focal epithelial hyperplasia: Case report. AB - The purpose of the present article is to present a 15 year-old patient with focal epithelial hyperplasia and to review the references on the subject-related etiological, pathological, diagnostic and treatment aspects. Focal epithelial hyperplasia is a rare human papilloma virus (HPV) related to oral lesion with very low frequency within our population. Surgical treatment with a biopsy was performed, acanthosis and parakeratosis are consistent histopathological features, since the patient had no history of sexual contact and HIV infection, the virus was probably acquired from environmental sources. PMID- 22071420 TI - Effect of ZnCl2 on plaque growth and biofilm vitality. AB - OBJECTIVE: The aim of this study was to evaluate the effects of ZnCl(2) on plaque growth and vitality pattern of dental biofilm and to determine the optimum zinc concentration for the inhibition of plaque formation. DESIGN: Data were collected from nine volunteers for whom a special-designed acrylic appliance was prescribed after a careful dental check up. The volunteers rinsed twice daily for 2min with ZnCl(2) of 2.5, 5, 10, 20mM as treatment and double distilled water (DDW) as control in respective assigned test weeks. The plaque index (PI) was assessed after 48h of appliance wearing. The glass discs with the adhered biofilm were removed from the splints and stained with two fluorescent dyes. The biofilm thickness (BT) and bacterial vitality of the whole biofilm as well as the mean bacterial vitality (BV) of the inner, middle and outer layers of biofilm were evaluated under confocal laser scanning microscope (CLSM). RESULTS: PI, BT and BV of biofilms treated by various concentrations of ZnCl(2) were reduced significantly when compared with the DDW group (p<0.05). PI, BT and BV of the 2.5mM ZnCl(2) group was significantly higher than groups of 5, 10, 20mM ZnCl(2) (p<0.05). The mean BV of the 3 layers (inner, middle and outer layers) showed that 2.5mM ZnCl(2) was the lowest concentration to inhibit BV in the outer layer, 5mM was the lowest concentration to extend this inhibition of BV to the middle layer, and none of the concentrations investigated in this study has shown any effect on bacteria inhibition in the inner layer. CONCLUSION: Zinc ions exhibited possible inhibitory effects on plaque formation, and have a promising potential to be used as an antibacterial agent in future dentifrices and mouthrinses. PMID- 22071421 TI - Editorial on "Capillary and microchip electrophoresis: challenging the common conceptions" by M.C. Breadmore. PMID- 22071422 TI - Generalized and rapid supramolecular solvent-based sample treatment for the determination of annatto in food. AB - A supramolecular solvent (SUPRA) made up of octanoic acid aggregates is proposed for the microextraction of bixin and norbixin, the two major components of the natural food colouring annatto, in food. The procedure involved the extraction of sub-gram quantities (200mg) of homogenized food with 0.8mL of the supramolecular solvent. The overall sample treatment took about 20 min, and several samples could be simultaneously treated using conventional lab equipment. No clean-up or solvent evaporation were required. Extraction efficiencies mainly depended on the major components making up the SUPRAS (i.e. octanoic acid and tetrahydrofuran) and were not affected by the pH or the temperature in the ranges studied (1-4 and 10-80 degrees C, respectively). Bixin and norbixin in the extracts were quantified by liquid chromatography (LC) and diode array detection (DAD). They were separated in a Hypersil C18 column using a mobile phase consisting of 5% acetic acid and methanol (15:85, v/v). The retention times for norbixin and bixin standards were 5.1 and 8.6 min, respectively. Recoveries in samples ranged between about 78% and 113%. The precision of the method, expressed as relative standard deviation, was about 1.5% and the quantitation limits for bixin and norbixin were 0.19 and 0.23 mg kg(-1), respectively, which were far below the maximum limits permitted by the European Union for the level of addition to food. Concentration of norbixin in samples belonging to the five major groups of food commodities defined in the literature, ranged between 3.75 and 43.8 mg kg(-1) whereas bixin was only found in one snack sample (6.6 mg kg(-1)). The method is simple and rapid, while delivering accurate and precise results, and can be used for the routine determination of annatto in food for the control of the compliance of current legislation. PMID- 22071423 TI - Technology trends in antibody purification. AB - This article reviews technology trends in antibody purification. Section 1 discusses non-chromatography methods, including precipitation, liquid-liquid extraction, and high performance tangential flow filtration. The second addresses chromatography methods. It begins with discussion of fluidized and fixed bed formats. It continues with stationary phase architecture: diffusive particles, perfusive particles, membranes and monoliths. The remainder of the section reviews recent innovations in size exclusion, anion exchange, cation exchange, hydrophobic interaction, immobilized metal affinity, mixed-mode, and bioaffinity chromatography. Section 3 addresses an emerging trend of formulating process buffers to prevent or correct anomalies in the antibodies being purified. Methods are discussed for preventing aggregate formation, dissociating antibody contaminant complexes, restoring native antibody from aggregates, and conserving or restoring native disulfide pairing. PMID- 22071424 TI - Effervescence-assisted dispersive micro-solid phase extraction. AB - Extraction techniques are surface dependent processes since their kinetic directly depends on the contact area between the sample and the extractant phase. The dispersion of the extractant (liquid or solid) increases this area improving the extraction efficiency. In this article, the dispersion of the sorbent at the very low milligram level is achieved by effervescence thanks to the in situ generation of carbon dioxide. For this purpose a special tablet containing the effervescence precursors (sodium carbonate as carbon dioxide source and sodium dihydrogen phosphate as proton donor) and the sorbent (OASIS-HLB) is fabricated. All the microextraction process takes place in a 10 mL-glass syringe and the solid, enriched with the extracted analytes, is recovered by filtration. Acetonitrile was selected to elute the retained analytes. The extraction mode is characterized and optimized using the determination of five nitroaromatic compounds in water. The absolute recoveries of the analytes were in the range 61 85% while relative recoveries close to 100% in all cases, which demonstrates the absence of matrix effect on the extraction. These values permit the determination of these analytes at the microgram per liter range with good precision (relative standard deviations lower than 6.1%) using ultra performance liquid chromatography (UPLC) combined with ultraviolet (UV) detection as instrumental technique. PMID- 22071425 TI - Liquid phase chromatography on microchips. AB - Over the past twenty years, the field of microfluidics has emerged providing one of the main enabling technologies to realize miniaturized chemical analysis systems, often referred to as micro-Total Analysis Systems (uTAS), or, more generally, Lab-on-a-Chip Systems (LOC) [1,2]. While microfluidics was driven forward a lot from the engineering side, especially with respect to ink jet and dispensing technology, the initial push and interest from the analytical chemistry community was through the desire to develop miniaturized sensors, detectors, and, very early on, separation systems. The initial almost explosive development of, in particular, chromatographic separation systems on microchips, has, however, slowed down in recent years. This review takes a closer, critical look at how liquid phase chromatography has been implemented in miniaturized formats over the past several years, what is important to keep in mind when developing or working with separations in a miniaturized format, and what challenges and pitfalls remain. PMID- 22071427 TI - Biomechanical analysis of pedicle screw thread differential design in an osteoporotic cadaver model. AB - BACKGROUND: Pedicle screw fixation, the standard surgical care for posterior stabilization in the thoraco-lumbar spine has a high rate of failure in osteoporotic individuals. Screw design factors and insertion techniques have been shown to influence the biomechanical performance of pedicle screws. Our objective was to investigate the biomechanical characteristics of pedicle screw fixation in osteoporotic bone by comparing standard screws with newly designed differential crest thickness dual lead screws. METHODS: An in-vitro spinal-level paired factorial study design was used to examine thoraco-lumbar spine biomechanical outcomes for differential pedicle screw thread designs. Six cadaveric human spines (T8-L5) were tested for six groups (n=20) consisting of 2 different crest thickness and 3 different insertion techniques. Bone mineral density was assessed and peak insertion torque measured while placing one screw of new design and control on the contralateral side. Screw pullout properties were measured from classical American Society for Testing and Materials protocols. FINDINGS: The screws designed specifically for osteoporotic bone showed significantly larger insertion torque compared with the standard screw design irrespective of insertion technique. Much of the variability in pullout failure and stiffness was explained by bone mineral density. The osteoporotic screws of different crest thickness were statistically similar to each other in all outcome measures. INTERPRETATION: Compared with standard pedicle screws, the dual lead osteoporotic specific pedicle screws demonstrated significantly larger insertion torques and similar pullout properties. Non-significant increased biomechanical strength was observed for thin crest compared to thick crest dual lead pedicle screws indicating their enhanced purchase in osteoporotic bone. PMID- 22071426 TI - Proximal and distal kinematics in female runners with patellofemoral pain. AB - BACKGROUND: Female runners have a high incidence of developing patellofemoral pain. Abnormal mechanics are thought to be an important contributing factor to patellofemoral pain. However, the contribution of abnormal trunk, hip, and foot mechanics to the development of patellofemoral pain within this cohort remains elusive. Therefore the aim of this study was to determine if significant differences during running exist in hip, trunk and foot kinematics between females with and without patellofemoral pain. METHODS: 32 female runners (16 patellofemoral pain, 16 healthy control) participated in this study. All individuals underwent an instrumented gait analysis. Between-group comparisons were made for hip adduction, hip internal rotation, contra-lateral pelvic drop, contra-lateral trunk lean, rearfoot eversion, tibial internal rotation, as well as forefoot dorsiflexion and abduction FINDINGS: The patellofemoral pain group had significantly greater peak hip adduction and hip internal rotation. No differences in contra-lateral pelvic drop were found. A trend towards reduced contra-lateral trunk lean was found in the patellofemoral pain group. No significant differences were found in any of the rearfoot or forefoot variables but significantly greater shank internal rotation was found in the patellofemoral pain group. INTERPRETATION: We found greater hip adduction, hip internal rotation and shank internal rotation in female runners with patellofemoral pain. We also found less contra-lateral trunk lean in the patellofemoral pain group. This may be a potential compensatory mechanism for the poor hip control seen. Rehabilitation programs that correct abnormal hip and shank kinematics are warranted in this population. PMID- 22071428 TI - Cortical bone drilling and thermal osteonecrosis. AB - BACKGROUND: Bone drilling is a common step in operative fracture treatment and reconstructive surgery. During drilling elevated bone temperature is generated. Temperatures above 47 degrees C cause thermal osteonecrosis which contributes to screw loosening and subsequently implant failures and refractures. METHODS: The current literature on bone drilling and thermal osteonecrosis is reviewed. The methodologies involved in the experimental and clinical studies are described and compared. FINDINGS: Areas which require further investigation are highlighted and the potential use of more precise experimental setup and future technologies are addressed. INTERPRETATION: Important drill and drilling parameters that could cause increase in bone temperature and hence thermal osteonecrosis are reviewed and discussed: drilling speed, drill feed rate, cooling, drill diameter, drill point angle, drill material and wearing, drilling depth, pre-drilling, drill geometry and bone cortical thickness. Experimental methods of temperature measurement during bone drilling are defined and thermal osteonecrosis is discussed with its pathophysiology, significance in bone surgery and methods for its minimization. PMID- 22071429 TI - Are the kinematics of the knee joint altered during the loading response phase of gait in individuals with concurrent knee osteoarthritis and complaints of joint instability? A dynamic stereo X-ray study. AB - BACKGROUND: Joint instability has been suggested as a risk factor for knee osteoarthritis and a cause of significant functional decline in those with symptomatic disease. However, the relationship between altered knee joint mechanics and self-reports of instability in individuals with knee osteoarthritis remains unclear. METHODS: Fourteen subjects with knee osteoarthritis and complaints of joint instability and 12 control volunteers with no history of knee disease were recruited for this study. Dynamic stereo X-ray technology was used to assess the three-dimensional kinematics of the knee joint during the loading response phase of gait. FINDINGS: Individuals with concurrent knee osteoarthritis and joint instability demonstrated significantly reduced flexion and internal/external rotation knee motion excursions during the loading response phase of gait (P<0.01), while the total abduction/adduction range of motion was increased (P<0.05). In addition, the coronal and transverse plane alignment of the knee joint at initial contact was significantly different (P<0.05) for individuals with concurrent knee osteoarthritis and joint instability. However, the anteroposterior and mediolateral tibiofemoral joint positions at initial contact and the corresponding total joint translations were similar between groups during the loading phase of gait. INTERPRETATIONS: The rotational patterns of tibiofemoral joint motion and joint alignments reported for individuals with concurrent knee osteoarthritis and joint instability are consistent with those previously established for individuals with knee osteoarthritis. Furthermore, the findings of similar translatory tibiofemoral motion between groups suggest that self-reports of episodic joint instability in individuals with knee osteoarthritis may not necessarily be associated with adaptive alterations in joint arthrokinematics. PMID- 22071430 TI - Simulated effect of reaction force redirection on the upper extremity mechanical demand imposed during manual wheelchair propulsion. AB - BACKGROUND: Manual wheelchair propulsion is associated with overuse injuries of the shoulder. Reaction force redirection relative to upper extremity segments was hypothesized as a means to redistribute mechanical load imposed on the upper extremity without decrements in wheelchair propulsion performance. METHODS: Two individuals performed wheelchair propulsion under simulated inclined (graded) conditions using self-selected control strategies. Upper extremity kinematics and reaction forces applied to the wheel were quantified and used as input into an experiment-based multi-link inverse dynamics model that incorporates participant specific experimental results. Reaction force direction was systematically modified to determine the mechanical demand imposed on the upper extremity (elbow and shoulder net joint moments and net joint forces) during wheelchair propulsion. Results were presented as solution spaces to examine the upper extremity load distribution characteristics within and between participants across a range of reaction force directions. FINDINGS: Redirection of the reaction force relative to the upper extremity segments provides multiple solutions for redistributing mechanical demand across the elbow and shoulder without decrements in manual wheelchair propulsion performance. The distribution of load across RF directions was participant specific and was found to vary with time during the push phase. INTERPRETATION: Solution spaces provide a mechanical basis for individualized interventions that aim to maintain function and redistribute load away from structures at risk for injury (e.g. reduce demand imposed on shoulder flexors (reduce shoulder net joint moment) or reduce potential for impingement (reduce shoulder net joint force). PMID- 22071431 TI - Type 2 diabetes control and complications in specialised diabetes care centres of six sub-Saharan African countries: the Diabcare Africa study. AB - AIM: The Diabcare Africa project was carried out across six sub-Saharan African countries to collect standardised and comparable information for the evaluation of diabetes control, management and late complications in diabetic populations at specialist clinics. METHODS: A cross-sectional, descriptive study of 2352 type-2 diabetes patients who were treated at specialist clinics for at least 12 months prior to the study. RESULTS: The mean age of patients was 53.0+/-16.0 years and had 8.0+/-6.0 years known duration of diabetes. 47% had their HbA1c assessed in the past year (mean 8.2+/-2.4%) with 29% achieving a level <6.5%. 21% had BP within 130/80 mmHg and 65% were treated for hypertension. Fasting lipids were assessed in 45% of the patients with mean cholesterol level of 4.9+/-1.2 mmol/L, HDL-cholesterol of 1.3+/-0.7 mmol/L and triglycerides of 1.2+/-0.7 mmol/L. 13% of the patients were treated for hyperlipidaemia, mostly with statins. Background retinopathy (18%) and cataract (14%) were the most common eye complications. Macrovascular disease was rare, and 48% had neuropathy. CONCLUSIONS: Half of the patients benefitted from standard care, and a third had appropriate glycaemic control - attributed to access to, rather than quality of care. This study provided evidence to support appropriate interventions to diabetic populations of sub-Saharan origin. PMID- 22071432 TI - Self-rated diabetes control in a Canadian population with type 2 diabetes: associations with health behaviours and outcomes. AB - AIMS: Diabetes control is a multifaceted process involving successful adherence to a self-care regimen as indicated by improved health outcomes. The aim of this study was to ascertain the construct validity of self-reported diabetes control in a population-based survey. METHODS: This study assessed 1848 participants with type 2 diabetes who took part in the Montreal Diabetes Health and Wellbeing Study in Quebec, Canada. Participants were administered the diabetes complications index as well as sociodemographic and health questions. RESULTS: Fair/poor diabetes control was associated with being less likely to check blood glucose weekly, being less likely to drink alcohol, being more likely to report being physically inactive, reporting fair/poor eating habits, being obese and having 1 or more diabetes complications. When all variables were included in a regression model the two variables most strongly associated with poor fair/poor diabetes control were reporting fair/poor eating habits (odds ratio 1.36, 95% CI 1.00 1.85) and having 2 or more diabetes complications (odds ratio 1.60, 95% CI 1.06 2.40). CONCLUSIONS: Results from this study indicate that self-rated diabetes control has associations with diabetes-specific self-care behaviours and outcomes, and is a general indicator of self-care and diabetes-related complications in a population-based survey. PMID- 22071433 TI - Carotid intima-media thickness, but not visceral fat area or adiponectin, correlates with intracoronary stenosis detected by multislice computed tomography in people with type 2 diabetes and hypertension. AB - We investigated the relationship between intracoronary stenosis detected by multislice computed tomography and various clinical parameters in type 2 diabetic patients with hypertension treated with candesartan (n=42). The results showed that carotid intima-media thickness, but not visceral fat area or adiponectin, correlated significantly with intracoronary stenosis (p<0.05). PMID- 22071434 TI - Usefulness of hemoglobin A1c as a criterion of dysglycemia in the definition of metabolic syndrome in Koreans. AB - To explore the utility of the HbA1c criterion in the definition of metabolic syndrome (MS) in Koreans, we cross-sectionally analyzed clinical and laboratory data on 11,293 non-diabetic Korean adults (aged 20-89 years, 34% women) collected during regular health checkups. Dysglycemia was defined as either fasting plasma glucose (FPG) >= 5.6 mmol/l or HbA1c >= 5.7%. The prevalence of MS as judged by the HbA1c criterion alone (17.8%) was significantly less than that determined by FPG level alone (24.5%). Use of a combination of both criteria slightly increased the prevalence of MS (26.0%). Among the 2953 subjects categorized as having MS using the combined criteria, 929 (31%) were diagnosed by the FPG criterion alone, 177 (6%) by the HbA1c criterion alone, and 1847 (63%) using both criteria. The group diagnosed using FPG values alone had significantly higher BMI, waist circumference, blood pressure, fasting plasma insulin levels, and insulin resistance index compared with those in the group diagnosed using HbA1c levels alone. In men, the brachial-ankle pulse wave velocity was significantly higher and the HDL-cholesterol level was lower in the HbA1c-alone group. Therefore, employment of the HbA1c criterion may be useful to define MS in subjects at increased risk for atherosclerosis. PMID- 22071435 TI - One-step synthesis of cubic FeS2 and flower-like FeSe2 particles by a solvothermal reduction process. AB - In this paper, for the first time a simple batch process was utilized for the facile synthesis of cubic FeS(2) and flower-like FeSe(2). By adjusting the amount of solvents and surfactants added, pure pyrite FeS(2) with a defined crystalline structure was obtained. It was found that the reaction temperatures and iron sources had significant influence on the purities and morphologies of FeS(2) and FeSe(2) particles. Raman spectra of the FeS(2) and FeSe(2) samples presented characteristic peaks of S-S and Se-Se active modes at 337, 372 cm(-1), and 180, 217, 254 cm(-1), respectively. The absorption properties of the FeS(2) and FeSe(2) samples were also investigated and the results demonstrated that these samples had broad optical absorption in NIR. Moreover, the synthetic approach demonstrated here may be of great potential for the controlled synthesis of other metal chalcogenides. PMID- 22071436 TI - Effects of localised and global convection on thermal explosion in a parallel plate geometry. AB - During an exothermic reaction in a fluid, convection may ensue on a local scale and then develop to the scale of the entire vessel. In this work, we study the effects of both localised and global convection on thermal explosions occurring between parallel plates. Analytical relations are derived for the various transitions in regimes of convective and thermal behaviours. We show that these relations agree well with previous numerical work and with new simulations in the present investigation. We also determine analytically the time for onset of convection, as well as the temperature increase at that time, for stable and explosive systems. The effects of the Prandtl number of the fluid on the transitions between regimes are noted. PMID- 22071437 TI - Does magnetoreception mediate biological effects of power-frequency magnetic fields? AB - The question of possible biological effects of power-frequency magnetic fields (PF-MF) remains controversial, notably because no valid mechanism of interaction could be proposed so far for intensities relevant to human and animal exposure (e.g. such as near high-tension power lines). In rodents, however, a few consistent effects of weak PF-MF have been reported. These are, notably, influence on spatial memory and partial inhibition of melatonin secretion under long-lasting exposure. Recent developments in study of magnetoreception in mammals justify reviving the hypothesis previously proposed of the intervention of the magnetic sense in melatonin disruption by PF-MF. We revisit this hypothesis and revise and extend it with respect to current knowledge and, particularly, with respect to reported effects on spatial memory. Proposals are made for experimental testing of the hypothesis. We argue that these tests may provide further insight into mechanisms of biological interactions of PF-MF and also, into mechanisms of magnetoreception per se. PMID- 22071438 TI - Transport behavior and rice uptake of radiostrontium and radiocesium in flooded paddy soils contaminated in two contrasting ways. AB - In order to investigate the transport behavior and rice uptake of radiostrontium and radiocesium in flooded rice fields, lysimeter experiments with two paddy soils were performed in a greenhouse. A solution containing (85)Sr and (137)Cs was applied in two different ways - being mixed with the top soil 27 d before transplanting or being dropped to the surface water 1d after transplanting. Rice uptake was quantified with two kinds of transfer factor - TF(m) (dimensionless) and TF(a) (m(2)kg(-1)-dry) for the pre- and post-transplanting depositions, respectively. For brown rice, the TF(m) values of (85)Sr and (137)Cs differed between the soils by factors of 2 (1.6*10(-2) and 2.5*10(-2)) and 7 (2.2*10(-2) and 1.5*10(-1)), respectively. Corresponding factors by the TF(a) values were 2 (2.5*10(-4) and 4.4*10(-4)) for (85)Sr and 3 (1.1*10(-3) and 2.9*10(-3)) for (137)Cs. Straws had several times higher TF(m) and TF(a) values of (85)Sr than of (137)Cs. The surface-water concentrations were substantially higher for the TF(a) than for the TF(m), indicating the possibility of a much higher plant-base uptake for the TF(a). In the TF(a) soils, (137)Cs and, to a lesser degree, (85)Sr were severely localized towards the soil surface, probably leading to an increased root uptake. The activity loss due to plant uptake and water percolation was generally inconsiderable. Time-dependent K(d) values of (85)Sr measured in a parallel experiment ranged from 20 to 170, whereas (137)Cs had much higher K(d) values. The use of TF(a) values instead of TF(m) values turned out to be a reasonable approach to the evaluation of a vegetation-period deposition. PMID- 22071439 TI - Survival following lung transplantation for silicosis and other occupational lung diseases. AB - BACKGROUND: Information is scant assessing outcomes in lung transplantation (LT) in advanced occupational lung diseases (OLD). AIMS: To analyse survival after LT for OLD. METHODS: Using data from the US Organ Procurement and Transplantation Network Registry (OPTN-R), we identified subjects aged >= 18 years transplanted for OLD from 2005 to 2010. OPTN-R selected referents of corresponding age, sex and body mass index (BMI) who underwent LT for other diagnoses were also identified. Post-LT survival time was estimated with Cox proportional hazard models. Baseline age, BMI, forced expiratory volume in 1 s, creatinine, lung allocation score, donor age, donor lung ischaemic time and transplant type (single versus bilateral) were included as covariates. Time-dependent covariates were used to model differences in relative risk over time. RESULTS: Thirty-seven males underwent LT for silicosis (n = 19) or other OLD (n = 18) during the analytic period (0.5% of all LTs). For non-silicotic OLD, 6-month and 1- and 3 year survival estimates were 66, 55 and 55%, compared with the silicotic group (86, 86 and 76%) and referent group (89, 84 and 67%). During the first year post transplant, those with OLD (silicosis and others combined) manifested an overall 2-fold increased mortality risk [hazard ratio (HR) 2.3, 95% CI 1.3-4.4; P < 0.05] compared to referents. In stratified analysis, this increased risk of death was restricted to those with non-silicotic OLD (HR 3.1, 95% CI 1.5-6.6; P < 0.01). Poorer survival was limited to the first year post-LT. CONCLUSIONS: Subjects undergoing LT for OLD other than silicosis may be at increased risk of death in the first year post-transplantation. PMID- 22071440 TI - [Long-term results of surgical treatment of scaphoid non union: influence of the correction of dorsal intercalated segment instability]. AB - OBJECTIVES: The publications dealing with scaphoid non-union emphasize importance of correction of the Dorsal Intercalated Segment Instability (DISI) to achieve good functional results and to prevent osteoarthritis. The purpose of this study was to assess, over 10 years follow-up, the functional outcomes of 25 patients with scaphoid non-union surgery. X-ray and DISI deformity were assessed. METHODS: Between 1994 and 1998, 53 patients underwent surgery for scaphoid non-union. Over 10 years follow-up, functional evaluation based on pain, QuickDASH and Mayo Wrist Score was performed, and a physical examination including mobility, strength and pain on the region of the scaphoid. Outcomes on X-rays were assessed by searching osteoarthritis damages and by measuring carpal height index and intracarpal angles. RESULTS: Eight patients had pain on the scaphotrapeziotrapezoidal joint without degenerative lesions on radiography. Compared to other patients, they had worse functional results, decrease of scapholunate angle, decrease of the DISI and increase of carpal height. CONCLUSIONS: The correction of the DISI is not always associated with good functional results. Although there were no osteoarthritic changes on the radiography, residual pain may be related to affection of the scapho-trapezo-trapezoidal joint. Surgical treatment with osteotomy of the scaphoid seems to be dangerous because of the moderate impact on function for these patients. PMID- 22071441 TI - Support for self-management of cardiovascular disease by people with learning disabilities. AB - BACKGROUND: Cardiovascular disease (CVD) is the second most common cause of death among people with learning disabilities (LD), and lifestyle has been linked to risk factors. With a shift towards illness prevention and self-management support, it is important to know how people with LD can be involved in this process. OBJECTIVE: To elicit the perceptions of people with LD, carers and health professionals regarding supported self-management of CVD. METHODS: A qualitative approach used in-depth semi-structured interviews based on vignettes with accompanying pictures. Fourteen people with LD, 11 carers/care staff and 11 health professionals were recruited and interviewed. Thematic framework analysis was used to analyse interview data. RESULTS: In total, 11 men and 25 women were interviewed. All respondents contributed views of self-management with a wide range of opinions expressed within each participant group. Four key themes encompassed: strategies for self-management; understanding the prerequisites for self-management support; preferred supporters and challenges for self-management implementation. Facilitated service user involvement in self-management decision making was highly valued in all groups. Service users wished for co-ordinated incremental support from across agencies and individuals. CONCLUSIONS: People with LD can be effectively consulted regarding health management and their views can inform service development. Promoting joined-up support across health and social care and families will require investment in resources, education and dismantling of professional barriers. PMID- 22071442 TI - Evaluation of laser diode thermal desorption (LDTD) coupled with tandem mass spectrometry (MS/MS) for support of in vitro drug discovery assays: increasing scope, robustness and throughput of the LDTD technique for use with chemically diverse compound libraries. AB - Within the drug discovery environment, the key process in optimising the chemistry of a structural series toward a potential drug candidate is the design, make and test cycle, in which the primary screens consist of a number of in vitro assays, including metabolic stability, cytochrome P450 inhibition, and time dependent inhibition assays. These assays are often carried out using multiple drug compounds with chemically diverse structural features, often in a 96 well plate format for maximum time-efficiency, and are supported using rapid liquid chromatographic (LC) sample introduction with a tandem mass spectrometry (MS/MS) selected reaction monitoring (SRM) endpoint, taking around 6.5 h per plate. To provide a faster time-to-decision at this critical point, there exists a requirement for higher sample throughput and a robust, well-characterized analytical alternative. This paper presents a detailed evaluation of laser diode thermal desorption (LDTD), a relatively new ambient sample ionization technique, for compound screening assays. By systematic modification of typical LDTD instrumentation and workflow, and providing deeper understanding around overcoming a number of key issues, this work establishes LDTD as a practical, rapid alternative to conventional LC-MS/MS in drug discovery, without need for extensive sample preparation or expensive, scope-limiting internal standards. Analysis of both the five and three cytochrome P450 competitive inhibition assay samples by LDTD gave improved sample throughput (0.75 h per plate) and provided comparable data quality as the IC50 values obtained were within 3 fold of those calculated from the LC-MS/MS data. Additionally when applied generically to a chemically diverse library of over 250 proprietary compounds from the AstraZeneca design, make and test cycle, LDTD demonstrated a success rate of 98%. PMID- 22071443 TI - Simultaneous quantification of polymethoxylated flavones and coumarins in Fructus aurantii and Fructus aurantii immaturus using HPLC-ESI-MS/MS. AB - The major lipid-soluble constituents in Fructus aurantii (zhiqiao) and Fructus aurantii immaturus (zhishi) are polymethoxylated flavones (PMFs) and coumarins. In the present study, a high-performance liquid chromatography with electrospray ionization tandem mass spectrometry method was developed to quantify PMFs (nobiletin, tangeretin, 5-hydroxy-6,7,8,4'-tetramethoxyflavone, and natsudaidai) and coumarins (marmin, meranzin hydrate, and auraptene) simultaneously. PMFs and coumarins were detected by electrospray ionization tandem mass spectrometry in positive ion mode and quantified with multiple reaction monitor. Samples were separated on a Diamonsil C18 (150 mm * 4.6 mm, 5 MUm) column using acetonitrile and formic acid-water solution as a mobile phase in gradient mode with a flow rate at 0.5 mL/min. All calibration curves showed good linearity (r2 > 0.9977) within the test ranges. Variations of the intraday and interday precisions were less than 4.07%. The recoveries of the components were within the range of 95.79% 105.04% and the relative standard deviations were less than 3.82%. The method developed was validated with acceptable accuracy, precision, and extraction recoveries and can be applied for the identification and quantification of four PMFs and three coumarins in citrus herbs. PMID- 22071444 TI - Qualitative and quantitative analysis of the major constituents in Chinese medicinal preparation Guan-Xin-Ning injection by HPLC-DAD-ESI-MS(n). AB - Guan-Xin-Ning (GXN) injection, a traditional Chinese medicinal preparation consisting of Radix Salvia miltiorrhiza and Rhizoma Ligusticum chuanxiong, has been used to treat coronary heart disease and angina pectoris in China for decades. In this paper, a HPLC/DAD/ESI-MS(n) method was successfully developed for qualitative and quantitative analysis of the active components in GXN injection for the first time. 28 compounds were identified by comparison of their retention times and MS spectra (HPLC/DAD/ESI-MS(n)) with those elucidated standards or recorded literature. 19 of them (danshensu, furoic acid, 3-O caffeoylquinic acid, protocatechuic aldehyde, p-hydroxybenzoic acid, chlorogenic acid, caffeic acid, 4-O-caffeoylquinic acid, vanillin, 1,3-dicaffeoylquinic acid, 4-hydroxycinnamic acid, ferulic acid, senkyunolide I, senkyunolide H, isosalvianolic acid A, rosmarinic acid, salvianolic acid B, salvianolic acid A and isosalvianolic acid C) were simultaneously determined by HPLC-DAD quantitatively. The analytical method was validated and successfully applied for simultaneous determination of major components in GXN injections from seven different production batches, indicating that the proposed approach was applicable for the routine analysis and quality control of GXN injection. PMID- 22071445 TI - Development and validation of reversed phase high performance liquid chromatographic method for determination of moxonidine in the presence of its impurities. AB - A simple, rapid, isocratic reversed-phase high-performance liquid chromatographic method was developed and validated for the analysis of moxonidine and its impurities in tablet formulations. The chromatographic separation was achieved on a Symmetry shield C18 column (250 mm * 4.6 mm, 5 MUm) by employing a mobile phase consisting of methanol-potassium phosphate buffer (0.05 M) mixture (15:85, v/v) (pH 3.5) at a flow rate of 1 ml min-1; detection at 255 nm. Central composite design technique and response surface method were used to evaluate the effects of variations of selected factors (buffer pH value, column temperature, methanol content) in order to achieve the best isocratic separation within short analysis time (less than 10 min), as well as for robustness test considerations. The method fulfilled the validation criteria: specificity, linearity, accuracy, precision, limit of detection and limit of quantitation. The method was successfully applied for the analysis of commercial moxonidine tablets. PMID- 22071446 TI - Antimicrobial prospect of newly synthesized 1,3-thiazole derivatives. AB - A new series of 1,3-thiazole and benzo[d]thiazole derivatives 10-15 has been developed, characterized, and evaluated for in vitro antimicrobial activity at concentrations of 25-200 MUg/mL against Gram+ve organisms such as methicillin resistant Staphylococcus aureus (MRSA), Gram-ve organisms such as Escherichia coli (E. coli), and the fungal strain Aspergillus niger (A. niger) by the cup plate method. Ofloxacin and ketoconazole (10 MUg/mL) were used as reference standards for antibacterial and antifungal activity, respectively. Compounds 11 and 12 showed notable antibacterial and antifungal activities at higher concentrations (125-200 MUg/mL), whereas benzo[d]thiazole derivatives 13 and 14 were found to display significant antibacterial or antifungal activity (50-75 MUg/mL) against the Gram+ve, Gram-ve bacteria, or fungal cells used in the present study. In addition, a correlation between calculated and determined partition coefficient (log P) was established which allows future development of compounds within this series to be carried out based on calculated log P values. Moreover, compounds 13 and 14 show that the optimum logarithm of partition coefficient (log P) should be around 4. PMID- 22071447 TI - Chemical constituents of the Mexican mistletoe (Psittacanthus calyculatus). AB - A phytochemical study of the methanol-soluble fraction of an aqueous extract of a sample of Psittacanthus calyculatus collected from the host plant Prosopsis laevigata (Smooth Mesquite) using several techniques, including co-chromatography coupled with UV detection, chromatographic purifications and IR, NMR and MS studies, resulted in the identification of gallic acid, two flavonol-3-biosides and the nonprotein amino acid N-methyl-trans-4-hydroxy-L-proline. PMID- 22071448 TI - Home versus ambulatory blood pressure monitoring in the diagnosis of clinic resistant and true resistant hypertension. AB - Ambulatory blood pressure (ABP) monitoring is recommended as a standard method for the evaluation of resistant hypertension (RH). This study assessed the diagnostic value of home blood pressure (HBP) monitoring in RH. Subjects on stable treatment with >=3 antihypertensive drugs were included. Clinic RH (CRH) was defined as elevated clinic blood pressure and true RH (TRH) as elevated ABP. The diagnosis of CRH was verified by ABP and HBP monitoring. The diagnostic value of HBP was assessed by taking ABP as reference method. Threshold for hypertension diagnosis was >=135/85 mm Hg (systolic and/or diastolic) for HBP and awake ABP and >=140/90 mm Hg for clinic blood pressure. Among 73 subjects on >=3 antihypertensive drugs, 44 (60%) had CRH and 40 (55%) TRH. There was agreement between ABP and HBP in diagnosing CRH in 82% of the cases (26 subjects (59%) with CRH and 10 (23%) without CRH; kappa 0.59). Regarding the diagnosis of TRH, there was agreement between ABP and HBP in 74% of the cases (36 subjects (49%) with TRH and 18 (25%) without TRH; kappa 0.46). The sensitivity, specificity, and positive and negative predictive values of HBP in detecting CRH were 93%, 63%, and 81% and 83%, respectively, and TRH were 90%, 55%, and 71%, and 82%, respectively (ABP taken as reference method). These data suggest that HBP is a reliable alternative to ABP in the evaluation of RH. These methods are necessary in both uncontrolled and controlled subjects on triple therapy to detect the white coat phenomenon and also masked RH. PMID- 22071449 TI - Planar chiral (eta6-arene)Cr(CO)3 containing carboxylic acid derivatives: synthesis and use in the preparation of organometallic analogues of the antibiotic platensimycin. AB - With more and more organometallic compounds receiving attention for applications in medicinal organometallic chemistry, the need arises for stereoselective syntheses of more complicated structures containing organometallic moieties, for example as isosteric substitutes for organic drug candidates. Herein, the synthesis and characterization of both diastereomers of a planar chiral (eta(6) arene)Cr(CO)(3) containing carboxylic acid derivative, namely, 3-{eta(6)-(1, 2, 3, 4-tetrahydro-1-endo/exo-methyl-2-oxonaphthalen-1-yl) tricarbonylchromium(0)}propanoic acid (7 and 8) is reported. The molecular structures of both were confirmed by single crystal X-ray diffraction. The degree of diastereoselectivity in Cr(CO)(3) complexation with methyl/tert-butyl-3 (1,2,3,4-tetrahydro-1-methyl-2-oxonaphthalen-1-yl)propanoate (4a/4b) vs. the Michael addition of methyl/tert-butyl acrylate to (eta(6)-1-methyl-2 tetralone)Cr(CO)(3) (9) was also examined. In the latter case the alkylation was found to be completely diastereoselective and gave methyl/tert-butyl-3-{eta(6) (1, 2, 3, 4-tetrahydro-1-endo-methyl-2-oxonaphthalen-1-yl)-tricarbonylchromium (0)}propanoate (5a and 5b) in excellent yield. Both the carboxylic acids 7 and 8 were coupled with the aminoresorcyclic acid core to achieve diastereomeric bioorganometallics 15a and 15b based on the naturally occurring antibiotic platensimycin lead structure (1a, see Fig. 1). The newly synthesized bioorganometallics were tested against various Gram-positive and Gram-negative bacterial strains but show no promising antibacterial activity. PMID- 22071450 TI - Ventricular septal necrosis after blunt chest trauma. AB - Ventricular Septal Defect (VSD) after blunt chest trauma is a very rare traumatic affection. We report here a case of blunt chest injury-related VSD and pseudoaneurysm. A 30-year old male truck driver was referred from a trauma center to our hospital seven days after a blunt chest trauma and rib fracture. The patient had severe pulmonary edema and echocardiography showed large VSD. Several mechanisms are involved in the pathogenesis of this affection including an acute compression of the heart muscle between the sternum and the spine, leading to excessive changes in the intrathoracic and most likely the intracardiac pressure after blunt chest injury. Traumatical patients with the same symptoms may be at risk of sudden death. Therefore, a high grade of suspicion is mandatory even without solid evidence of myocardial damage on the initial evaluation. In continue some hidden angles of this case was discussed. Given the prognostic implications of traumatic VSD with associated pseudoaneurysm, its detection has critical value for preventing its clinical sequelae. PMID- 22071451 TI - Cancer treatment-induced oral mucositis: a critical review. AB - Head and neck cancer represents one of the main oncological problems. Its treatment, radiotherapy and chemotherapy leads to mucositis, and other side effects. The authors reviewed high-quality evidence published over the last 25 years on the treatment of cancer treatment-induced oral mucositis. A Medline search for double blind randomized controlled clinical trials between 1985 and 2010 was carried out. The keywords were oral mucositis, radiotherapy, chemotherapy, and head and neck. The different therapeutic approaches found for cancer treatment-induced oral mucositis included: intensive oral hygiene care; use of topical antiseptics and antimicrobial agents; use of anti-inflammatory agents; cytokines and growth factors; locally applied non-pharmacological methods; antioxidants; immune modulators; and homoeopathic agents. To date, no intervention has been able to prevent and treat oral mucositis on its own. It is necessary to combine interventions that act on the different phases of mucositis. It is still unclear which strategies reduce oral mucositis, as there is not enough evidence that describes a treatment with a proven efficiency and is superior to the other treatments for this condition. PMID- 22071452 TI - Pituitary volume mediates the relationship between pubertal timing and depressive symptoms during adolescence. AB - Early timing of puberty (i.e., advanced pubertal maturation relative to peers) has been linked to the onset of depressive symptoms during the early adolescent phase. However, the precise neurobiological mechanisms linking early pubertal timing to adolescent depressive symptoms are not clear. We investigated whether the volume of the pituitary gland, a key component of the hypothalamic-pituitary gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes, mediated the relationship between pubertal timing and depressive symptoms in 155 adolescents (72 females) both cross-sectionally and longitudinally. At baseline (M age 12.7, SD 0.5 years), early pubertal timing predicted larger pituitary gland volume and higher depressive symptoms (especially for girls), but there was no mediation effect. Longitudinally, however, larger pituitary gland volume at baseline was found to mediate the relationship between early pubertal timing and increased depressive symptoms over time (M follow-up period=2.57 years, SD=0.26) for both boys and girls. Our findings suggest that neurobiological mechanisms are partly responsible for the link between early pubertal timing and depressive symptoms in adolescents. We speculate that an enlarged pituitary gland in adolescents with early pubertal timing might be associated with hyperactivation of the hormonal stress response, leading to increased susceptibility to environmental stressors, and subsequent development of depressive symptoms. Given the well-established relationship between increasing depressive symptoms in adolescence and later disorder, these findings have implications for targeted prevention and early intervention strategies for depressive disorders in adolescence. PMID- 22071453 TI - Subtle regulation of the micro- and nanostructures of electrospun polystyrene fibers and their application in oil absorption. AB - In this study, we conducted a subtle regulation of micro- and nanostructures of electrospun polystyrene (PS) fibers via tuning the molecular weights of the polymers with different sources, solvent compositions, and solution concentration. The surface morphology and porous structures of as-prepared PS fibers were characterized, and a full and intuitive observation of the porous structures as well as a tentative account of the formation of porous structures was presented. Additionally, the porous PS fibrous mats showed much higher oil absorption capacities than those of commercial polypropylene fibers in the form of a non-woven fabric, which displays a bight future for oil spill cleanups. We believe that such regulation of micro- and nanostructures of the PS fibers will widen the range of their applications in self-cleaning materials, ultra-high sensitivity sensors, tissue engineering, ion exchange materials, etc. PMID- 22071454 TI - Integrated care for chronic conditions: the contribution of the ICCC Framework. AB - OBJECTIVE: The aim of this research is to highlight the current relevance of the Innovative Care for Chronic Conditions (ICCC) Framework, as a model for change in health systems towards better care for chronic conditions, as well as to assess its impact on health policy development and healthcare redesign to date. METHODS: The authors reviewed the literature to identify initiatives designed and implemented following the ICCC Framework. They also reviewed the evidence on the effectiveness, cost-effectiveness and feasibility of the ICCC and the earlier Chronic Care Model (CCM) that inspired it. RESULTS: The ICCC Framework has inspired a wide range of types of intervention and has been applied in a number of countries with diverse healthcare systems and socioeconomic contexts. The available evidence supports the effectiveness of this framework's components, although no study explicitly assessing its comprehensive implementation at a health system level has been found. CONCLUSIONS: As awareness of the need to reorient health systems towards better care for chronic patients grows, there is great potential for the ICCC Framework to serve as a road map for transformation, with its special emphasis on integration, and on the role of the community and of a positive political environment. PMID- 22071455 TI - Equity and equality in the use of GP services for elderly people: the Spanish case. AB - OBJECTIVES: To present new evidence both on the horizontal inequity in the delivery of primary health care and on the factors driving inequalities in the use of GP services for Spanish population aged 50 years and over. METHODS: Cross sectional study based on the Spanish sample of the Survey of Health, Aging and Retirement in Europe (SHARE) for 2006-07. We use the index proposed by Wagstaff and van Doorslaer (HI(WV)) to compute health care inequity. The concentration index measuring income related inequality in health care use is decomposed into the contribution of each determinant. RESULTS: Our results show the presence of pro-poor inequality in both the access and the frequency of use for GP services, which is mainly explained by unequal distribution of need factors. The contribution of non-need factors to income related inequality is quite higher for the conditional number of GP visits (48.13%) than for the probability of positive use (17.55%). We have also found significant pro-poor inequity in the probability of access to a GP and in the conditional number of visits for elderly people. CONCLUSIONS: The relevance of social determinants of health is confirmed, and hence the need for wide-scoped public policies to reduce health inequalities. At equal levels of need, rich and poor elderly people are not treated equally. As much as appropriateness of care provided is unknown, we cannot conclude that inequity in GP services really favours the lower income individuals in terms of health gains. PMID- 22071456 TI - Postauricular fascial flap and suture otoplasty: a prospective outcome study of 227 patients. AB - The anterior scoring technique is criticised for a higher risk of haematoma related complications while the suture techniques for suture-extrusion and recurrence. Horlock et. al. described a suture otoplasty with addition of a postauricular fascial flap to reduce suture extrusion and noted recurrence rates of 8%. We report the senior author's experience with this technique in 227 consecutive cases. All cases were done by or under supervision of the senior author and the data collected prospectively. Complications, recurrence, revision rate and results as recorded were analysed. A total of 10 (7 early 3 late) complications were recorded (4.4%). Suture extrusion (n = 6, 2.64%), Keloids (n = 3, 1.32%), Infection, anterior skin necrosis (n = 1 each, 0.44%). A total of 6 unilateral and 5 bilateral cases had a recurrence (3.67% total ears) and 97% of recorded outcomes were reported as good or excellent results. The low complication rate seems to support the hypothesis that the fascial flap prevents suture extrusion and reduces risk of recurrence. Lack of Anterior dissection avoids risks of bleeding and haematoma. PMID- 22071457 TI - A novel distraction technique to facilitate daycase paediatric surgery under local anaesthesia. PMID- 22071458 TI - Treatment of pectoralis major flap myospasms with botulinum toxin type A in head and neck reconstruction. AB - BACKGROUND: Treatment options for muscle spasm complications of the pectoralis major (PM) flap in head and neck reconstruction have hardly been investigated. The authors report their experience using botulinum toxin (BTX-A) injections as a treatment of PM flap myospasm complications in head and neck reconstruction. METHODS: From January 2005 to May 2009, 83 patients underwent PM flap reconstruction. Eleven of them reported muscle twitching as a post-operative complication and are therefore included in this study. As all 11 patients refused a second surgery, they were offered BTX-A injections. This group of patients was followed up at regular intervals with clinical examinations, digital photography, range of motion (ROM) of the neck in different vectors, and neck disability system (NDS) questionnaires. RESULTS: After the first BTX-A infiltration, muscle twitching decreased, the ROM values increased and, according to the NDS, patients' discomfort progressively decreased. Only two of the 11 patients required two additional BTX-A sessions. CONCLUSION: BTX-A infiltration is an effective non-invasive procedure that significantly reduces the PM muscular contraction in head and neck reconstruction. PMID- 22071459 TI - Primary restoration of elbow flexion in adult post-traumatic plexopathy patients. AB - Restoration of elbow flexion is one of the priorities in brachial plexus palsy, as this function brings the hand to the mouth. This study analyses the results of musculocutaneous nerve reconstruction in 194 patients with devastating paralysis. Results were analyzed in relation to denervation time, severity score, length of nerve grafts, and donor nerves used. Between 1978 and 2006, 194 post-traumatic plexopathy patients underwent musculocutaneous nerve reconstruction. 298 motor donors were used in 175 patients while 19 patients had microneurolysis. There were 104 intraplexus motor donors; 124 intercostal nerves were transferred in 39 patients; direct coaptation was performed in 31 patients and three or more intercostals were transferred in 33 patients; 16 patients underwent musculocutaneous to musculocutaneous repair. 144 patients had interposition nerve grafts. The mean follow-up was 4.48 +/- 2.78 years. Results were good or excellent (>=M3+) in 52.53% of patients with more than 70 degrees of elbow flexion. Patients, who were operated on less than 4 months from injury, with high severity score, attained significant better results than late cases with multiple root avulsions. Intraplexus donors have direct influence on biceps recovery, achieving significant better results than extraplexus donors. Intercostal nerves are an alternative source in avulsion injuries. The use of 3 intercostals with direct coaptation yielded optimal elbow flexion. Musculocutaneous nerve reconstruction is one of the priorities in upper limb reanimation. Functional outcomes are influenced by the age of the patient, severity of plexus lesion, denervation time, and type of reconstruction. Early surgery is recommended. PMID- 22071460 TI - Levetiracetam-induced interstitial nephritis in a patient with glioma. AB - A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline. PMID- 22071461 TI - The impact of changing intracranial aneurysm practice on the education of cerebrovascular neurosurgeons. AB - Endovascular repair of intracranial aneurysms has transformed the practice of cerebrovascular surgery. We reviewed the National Hospital Morbidity Database in Australia for the years 2000 to 2008 and investigated the changing trends of aneurysm practice. During this period 7,503 craniotomies for aneurysm repair and 7,863 endovascular coiling procedures were performed. The number of aneurysm procedures performed surgically reduced from 9 cases per neurosurgeon per year to 4.2 cases, a reduction of 53.3%. The number of endovascular treatments increased 2.1 fold, from 3.6 aneurysms per neurosurgeon in 2000 to 7.5 in 2008. The implications of reduced numbers of surgically treated aneurysms were considered for the education of cerebrovascular neurosurgeons in Australia. PMID- 22071462 TI - Diagnosis and management of optic nerve glioma. AB - Optic nerve gliomas are highly variable tumours with an unpredictable clinical course. Consequently, the diagnosis and management of these tumours remains complex and a standardised management strategy does not exist. In this paper we describe a patient with optic nerve glioma treated at our institution and then review recent advances made in the diagnosis and treatment of these tumours over the past 10 years. Our aim is to clarify current best practice in the management of optic nerve gliomas. PMID- 22071463 TI - Biologics in relapsing polychondritis: a literature review. AB - BACKGROUND: There is no standardized therapeutic protocol for relapsing polychondritis (RP). Emergence of biologics holds much hope in the management of this connective tissue disease. OBJECTIVES: To evaluate the efficacy and safety of biologics in patients with active RP. METHODS: A systematic review of the literature using PubMed was performed through December 2010. MeSH terms and keywords were used relating to RP and biologics. All papers reporting the efficacy and/or safety of biologics in RP were selected. Reference lists of included papers were also searched. RESULTS: All publications relate to case series or isolated case reports. No randomized controlled trial has been performed. Thirty papers that included 62 patients were published. These patients were treated with TNFalpha blockers (n = 43), rituximab (n = 11), anakinra (n = 5), tocilizumab (n = 2), and abatacept (n = 1). The endpoint of treatment differs from 1 publication to the other and therefore makes the comparison of efficacy among the various biologics difficult. Biologics were effective in 27 patients, partially effective in 5 patients, and not effective in 29 patients. Safety appeared to be good. However, 4 deaths were recorded (2 sepsis, 1 postoperatively after aortic aneurysm surgery, and 1 after accidental dislocation of the tracheostomy device). CONCLUSIONS: The experience with biologics in RP is very limited and their real efficacy and indications need to be better defined. Randomized controlled trials, although difficult to perform because of the rarity of RP, are needed to determine the place of biologics in the treatment strategy of this orphan disease. PMID- 22071464 TI - Electron transfer processes in potassium collisions with 5-fluorouracil and 5 chlorouracil. AB - Electron transfer to uracil (U), 5-chlorouracil (5-ClU) and 5-fluorouracil (5-FU) yielding anion formation has been investigated in 30-100 eV potassium-molecule collisions. The rich fragmentation patterns of all three molecules suggest that electron transfer in collisions with electronegative neutrals may cause efficient damage to RNA. The main ring fragment anion in all the mass spectra was NCO(-) while the production of X(-) (X = F, Cl) was a strong decomposition of the halouracil temporary negative ions. Cl(-) was the most intense fragment anion in the 5-chlorouracil measurements, whereas NCO(-) production dominated in the U and 5-FU data. Arguments based on energetics and vibrational dynamics have been proposed to explain these differences. Electronic coupling between dipole- and valence-bound states may play a particularly important role in the fragmentation pathways of the 5-ClU parent anion. The stabilizing influence of the potassium cation following electron transfer (ionic scattering) on the observed fragmentation patterns is discussed, notably in the context of comparisons with free electron attachment processes. PMID- 22071465 TI - High intrafamilial variability in autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy: a case study. AB - INTRODUCTION: Autoimmune polyendocrinopathy- candidiasis-ectodermal-dystrophy syndrome (APECED) is a monogenic disease whose phenotype may reveal wide heterogeneity. The reasons of this variability still remain obscure. PATIENTS AND METHODS: Two APECED siblings with identical genotype and extremely different phenotype were compared with regard to exposure to infectious triggers, autoantibodies' profile, mechanisms of peripheral tolerance, and human leukocyte antigen (HLA) haplotype. The following infectious markers were evaluated: rubella, Epstein Barr virus, cytomegalovirus, toxoplasma, varicella zoster virus, parvovirus B19, herpes simplex virus, and parainfluenza virus. APECED-related autoantibodies were detected by indirect immunofluorescence or complement fixation or enzyme- linked immunosorbent assay or radioimmunoassay. Resistance to Fas-induced apoptosis was evaluated on peripheral blood mononuclear cells (PBMC) activated with phytohemoagglutinin, the number of TCD4+CD25+ regulatory cells (Treg) was evaluated through flow-cytometry and natural killer (NK) activity through Wallac method. Perforin (PRF1) was amplified by PCR and sequenced. RESULTS: No difference was observed between the siblings in common infectious triggers, extent of Fas-induced apoptosis, NK-cell activity and PRF1 sequence, the number of Tregs and HLA haplotypes. CONCLUSION: Although APECED is a monogenic disease, its expressivity may be extremely different even in the same family. This variability cannot be explained by common triggering infectious agents or functional alterations of mechanisms governing peripheral tolerance. PMID- 22071468 TI - Cannulation of the right axillary artery for extracorporeal circulation in aortic surgery through a left thoracotomy: a novel technique. AB - Extensive aortic disease, such as atherosclerosis with aneurysms or dissections that involve the ascending aorta, can complicate the choice of a cannulation site for cardiopulmonary bypass. Antegrade selective cerebral perfusion through the right axillary artery has proved to be a reliable and valuable method for cerebral protection in aortic surgery. In the supine position it is an artery straightforward to access, it is more complicated in the right thoracoabdominal position. We present an innovative method of axillary artery cannulation for patients requiring surgery through a left thoracotomy. PMID- 22071470 TI - Timing of gangrene tissue debridement after autologous bone marrow cell implantation in patients with superficial femoral arterial occlusion: preliminary experiences. AB - AIM: Although implantation of bone marrow mononuclear cells (BMI) was shown to improve outcomes in patients with severe peripheral arterial occlusive disease (PAOD), little experience has been reported in patients with an arterial occlusion level above the knee, ischemic gangrene, and high cardiovascular risk. This study sought to investigate the timing of gangrene tissue debridement and the safety of BMI in these patients. METHODS: Six "no-option" PAOD patients were enrolled with an arterial occlusion level above the knee, ischemic gangrene, and 3 systemic diseases related to a high cardiovascular risk. The ischemic status was evaluated by measuring the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and wound healing after BMI. RESULTS: All patients safely underwent the procedures with intravenous general anesthesia by titrating propofol. Major lower extremity amputation, minor debridement amputation, and debridement surgery were performed in 2 (33.3%), 1 (16.7%), and 2 (33.3%) patients, respectively, 3.1 2.8 months after BMI. Compared to the amputation group (N=3), the salvage group (N=3) had a significantly higher baseline ABI (P=0.02) and a shorter distance between the gangrene site and arterial occlusion site (P=0.01). In the 3 patients who underwent debridement, ABI and TcPO2 significantly improved 1 month after BMI, and gangrenous tissues were debrided 3.8 +/- 3.6 (range, 1~8) months after BMI with complete healing within 1 month. CONCLUSION: Autologous BMI therapy is safe in patients at high cardiovascular risk with an arterial occlusion level above the knee and ischemic gangrene. Effective predictors of BMI include the baseline ABI and distance to the ischemia. Gangrene tissue should be debrided at least 1 month after BMI. PMID- 22071471 TI - BRAVISSIMO study: 12-month results from the TASC A/B subgroup. AB - AIM: The BRAVISSIMO study is a prospective, non-randomized, multicenter, multinational, monitored trial, conducted at 12 hospitals in Belgium and 11 hospitals in Italy. This manuscript reports on the BRAVISSIMO TASC A&B iliac lesion cohort, based on data collected up to the 13-month time point. The primary endpoint of the study is primary patency at 12 months, defined as a target lesion without a hemodynamically significant stenosis on duplex ultrasound (>50%, systolic velocity ratio no greater than 2.0) and without Target Lesion Revascularization (TLR) within 12 months. METHODS: Between July 2009 and February 2010, a total of 190 patients who presented with TASC A or TASC B aorto-iliac lesions were included, of which 140 patients were enrolled in Belgium and 50 in Italy. RESULTS: The demographic data were comparable for the TASC A and TASC B patients groups. The number of occlusions, the average degree of stenosis, the average lesion length was significantly higher in the group of TASC B lesions, which is congruent with the TASC lesions definitions. Similarly, there were significantly more unilateral lesions in the TASC A group, compared to the TASC B group. The 12-month primary patency rate was 94.0% for TASC A lesions and 96.5% for TASC B lesions, which is not statistically significant. The 12-month primary patency rate was 92.9% in lesions treated with the Omnilink Elite stent, 97.1% in lesions treated with the Absolute Pro stent groups, and 100% in lesions treated with both stents. CONCLUSION: Our findings confirm that endovascular therapy, and more specifically primary stenting, is the preferred treatment for patients with TASC A/B aortoiliac lesions. Currently, we are collecting the 12-month data for the TASC C/D subgroup in the BRAVISSIMO study. Upon release of the results from this subgroup, we will be able to compare the results from both arms of this large-scale international study. PMID- 22071472 TI - Supramolecular isomerism and solvatomorphism in a novel coordination compound. AB - Three different crystal forms were obtained from the crystallisation of a flexible imidazole based ligand and CdBr(2) under different conditions. Structural analysis reveals that the correlation between the three metallocyclic compounds can be described in terms of isostructurality, solvatomorphism and supramolecular isomerism. PMID- 22071473 TI - Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose-dependent effect. AB - Loss-of-function variants within the filaggrin gene (FLG) increase the risk of atopic dermatitis. FLG also demonstrates intragenic copy number variation (CNV), with alleles encoding 10, 11, or 12 filaggrin monomers; hence, CNV may affect the amount of filaggrin expressed in the epidermis. A total of 876 Irish pediatric atopic dermatitis cases were compared with 928 population controls to test the hypothesis that CNV within FLG affects the risk of atopic dermatitis independently of FLG-null mutations. Cases and controls were screened for CNV and common FLG-null mutations. In this population the 11-repeat allele was most prevalent (allele frequency 51.5%); the 10-repeat allele frequency was 33.9% and the 12-repeat allele frequency was 14.6%. Having excluded FLG mutation carriers, the control group had a significantly higher number of repeats than cases (chi(2) P=0.043), and the odds ratio of disease was reduced by a factor of 0.88 (95% confidence interval 0.78-0.98, P=0.025) for each additional unit of copy number. Breakdown products of filaggrin were quantified in tape-stripped stratum corneum from 31 atopic dermatitis patients and urocanic acid showed a positive correlation with total copy number. CNV within FLG makes a significant, dose dependent contribution to atopic dermatitis risk, and therefore treatments to increase filaggrin expression may have therapeutic utility. PMID- 22071474 TI - The contribution of health services research to improved dermatologic care. AB - To translate scientific discovery into improved health, we must study health care itself; i.e., how people access health care, costs or other barriers to the provision of good care, and what happens to patients as a result of this care. Health services research (HSR) is the interdisciplinary field that studies health care and its effects. This paper reviews different types of HSR and highlights some dermatologic examples that have resulted in improved health-care systems or have helped us understand access to existing systems. The paper also addresses some of the political and systematic challenges for health services research overall, and for individual investigators and program leaders. PMID- 22071475 TI - High soluble CD30, CD25, and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides. AB - Histopathology alone cannot predict the outcome of patients with CD30+ primary cutaneous lymphoproliferative disorders (CD30CLPD) and early mycosis fungoides (MF). To test the hypothesis that serum cytokines/cytokine receptors provide prognostic information in these disorders, we measured soluble CD30 (sCD30), sCD25, and selected cytokines in cell cultures and sera of 116 patients with CD30CLPD and 96 patients with early MF followed up to 20 years. Significant positive correlation was found between sCD30 levels and sCD25, CD40L, IL-6, and IL-8, suggesting that CD30+ neoplastic cells secrete these cytokines, but not Th2 cytokines. In vitro studies confirmed that sCD30, sCD25, IL-6, and IL-8 are secreted by CD30CLPD-derived cell lines. CD30CLPD patients with above normal sCD30 and sCD25 levels had worse overall and disease-related survivals, but only sCD30 retained significance in Cox models that included advanced age. High sCD30 also identified patients with worse survival in early MF. Increased IL-6 and IL-8 levels correlated with poor disease-related survival in CD30CLPD patients. We conclude that (1) neoplastic cells of some CD30CLPD patients do not resemble Th2 cells, and that (2) high serum sCD30, sCD25, IL-6, and perhaps IL-8 levels may provide prognostic information useful for patient management. PMID- 22071476 TI - Lymphatic dysfunction impairs antigen-specific immunization, but augments tissue swelling following contact with allergens. AB - The lymph transports tissue-resident dendritic cells (DCs) to regional lymph nodes (LNs), having important roles in immune function. The biological effects on tissue inflammation following lymphatic flow obstruction in vivo, however, are not fully known. In this study, we investigated the role of the lymphatic system in contact hypersensitivity (CHS) responses using k-cyclin transgenic (kCYC(+/-)) mice, which demonstrate severe lymphatic dysfunction. kCYC(+/-) mice showed enhanced ear swelling to both DNFB and FITC, as well as stronger irritant responses to croton oil compared with wild-type littermates. Consistently, challenged ears of kCYC(+/-) mice exhibited massive infiltrates of inflammatory cells. In contrast, DC migration to regional LNs, drainage of cell-free antigen to LNs, antigen-specific IFN-gamma production, and lymphocyte proliferation were impaired during the sensitization phase of CHS in kCYC(+/-) mice. Transfer experiments using lymphocytes from sensitized mice and real-time PCR analysis of cytokine expression using challenged ear revealed that ear swelling was enhanced because of impaired lymphatic flow. Collectively, we conclude that insufficient lymphatic drainage augments apparent inflammation to topically applied allergens and irritants. The findings add insight into the clinical problem of allergic and irritant contact dermatitis that commonly occurs in humans with peripheral edema of the lower legs. PMID- 22071478 TI - Development of lentigines in German and Japanese women correlates with variants in the SLC45A2 gene. PMID- 22071477 TI - A subset of methylated CpG sites differentiate psoriatic from normal skin. AB - Psoriasis is a chronic inflammatory immune-mediated disorder affecting the skin and other organs including joints. Over 1,300 transcripts are altered in psoriatic involved skin compared with normal skin. However, to our knowledge, global epigenetic profiling of psoriatic skin is previously unreported. Here, we describe a genome-wide study of altered CpG methylation in psoriatic skin. We determined the methylation levels at 27,578 CpG sites in skin samples from individuals with psoriasis (12 involved, 8 uninvolved) and 10 unaffected individuals. CpG methylation of involved skin differed from normal skin at 1,108 sites. Twelve mapped to the epidermal differentiation complex, upstream or within genes that are highly upregulated in psoriasis. Hierarchical clustering of 50 of the top differentially methylated (DM) sites separated psoriatic from normal skin samples with uninvolved skin exhibiting intermediate methylation. CpG sites where methylation was correlated with gene expression are reported. Sites with inverse correlations between methylation and nearby gene expression include those of KYNU, OAS2, S100A12, and SERPINB3, whose strong transcriptional upregulation is an important discriminator of psoriasis. Pyrosequencing of bisulfite-treated DNA from skin biopsies at three DM loci confirmed earlier findings and revealed reversion of methylation levels toward the non-psoriatic state after 1 month of anti-TNF-alpha therapy. PMID- 22071479 TI - Complex roles for VEGF in dermal wound healing. PMID- 22071481 TI - A magnetically separable photocatalyst based on nest-like gamma-Fe2O3/ZnO double shelled hollow structures with enhanced photocatalytic activity. AB - Magnetic nest-like gamma-Fe(2)O(3)/ZnO double-shelled hollow nanostructures have been successfully synthesized via a multi-step process. The materials have been thoroughly characterized by different techniques. These interesting nest-like hollow nanostructures are composed of ZnO nanoflakes grown on the surface of gamma-Fe(2)O(3) hollow spheres. Importantly, these magnetic hollow nanostructures show very high visible-light photocatalytic activity for the degradation of different organic dyes including methylene blue (MB), Rhodamine-B (RhB), and methyl orange (MO). It is further demonstrated that these gamma-Fe(2)O(3)/ZnO hybrid photocatalysts are highly stable and can be used repeatedly. PMID- 22071480 TI - Sleep and immune function. AB - Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep-wake cycle showed that immune parameters like numbers of undifferentiated naive T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations. PMID- 22071482 TI - Determinants of progression of aortic valve stenosis and outcome of adverse events in hemodialysis patients. AB - BACKGROUND: Hemodialysis (HD) is an important risk factor for progression of aortic valve stenosis (AS). However, there are varying degrees of disease progression among patients with AS on HD. The aim of this study was to find determinants of rapid progression of AS in patients on HD. METHODS: We enrolled 30 patients with AS on HD with a mean follow-up period of 4 years. The peak pressure gradient (PPG) between the initial echocardiography and the last echocardiography at least 3 months interval (DeltaPPG) was adopted as the indicator of AS progression. We divided the patients into two groups according to DeltaPPG per year [rapid progression (DeltaPPG>4.5 mmHg/year), slow progression (DeltaPPG<4.5 mmHg/year)] and compared the clinical characteristics between the two groups. RESULTS: Overall mean DeltaPPG was 4.5 mmHg/year. Systolic blood pressure (SBP), serum calcium, and calcium-phosphate product were significantly higher in rapid progression group compared with slow progression group (p<0.05). CONCLUSION: High systolic blood pressure, serum calcium, and calcium-phosphate product were associated with rapid progression of AS in patients on chronic HD. PMID- 22071483 TI - The effect of growth hormone deficiency on size-corrected bone mineral measures in pre-pubertal children. AB - Growth hormone deficiency (GHD) in children has been frequently perceived to be a cause of low bone mass accrual. The confounding effects of poor growth limit the interpretation of prior studies of bone health in GHD. We studied size-corrected bone mineral measures in 30 pre-pubertal GHD children and 75 healthy controls. Our study shows that size-corrected whole-body bone mineral content of GHD children were comparable with controls. INTRODUCTION: The purpose of this study is to evaluate the effects of GHD on size-corrected bone measures at the lumbar spine (LS) and the whole body (WB). METHODS: LS bone area (BA), LS bone mineral content (BMC), WB BA, WB BMC, and lean body mass (LBM) were measured in 30 pre pubertal GHD children and 75 controls by dual-energy X-ray absorptiometry. Multiple linear regressions were used to calculate size-corrected (Sc) LS BA(Sc), LS BMC(Sc), WB BA(Sc), and WB BMC(Sc) from control subjects using height and age as independent variables. Furthermore, the relationship between muscle and bone was studied by first assessing LBM for height (LBM(Ht)) and then determining WB BMC for LBM (WB BMC(LBM)). All values were converted to Z-scores and compared with the control. RESULTS: At diagnosis, WB BMC(Sc) Z-score of GHD children was not significantly different from controls. However, mean Z-scores of LS BA(Sc) ( 0.89 +/- 0.84, p < 0.0001), LS BMC(Sc) (-0.70 +/- 1.1, p < 0.001), WB BA(Sc) ( 0.65 +/- 1.0, p < 0.006), and LBM(Ht) (-0.66 +/- 1.7, p < 0.01) were significantly reduced, and WB BMC(Lbm) (0.78 +/- 1.5, p < 0.003) was significantly higher in GHD children than controls. CONCLUSION: Size-corrected WB BMC of GHD children were comparable with controls, and bones were normally adapted for muscle mass. Determinants of bone strength which may primarily be affected by GHD are muscle mass, bone size, and geometry rather than bone mass. PMID- 22071484 TI - Assessing attentional systems in children with Attention Deficit Hyperactivity Disorder. AB - The aim of this study was to evaluate the efficiency and interactions of attentional systems in children with Attention Deficit Hyperactivity Disorder (ADHD) by considering the effects of reinforcement and auditory warning on each component of attention. Thirty-six drug-naive children (18 children with ADHD/18 typically developing children) performed two revised versions of the Attentional Network Test, which assess the efficiency of alerting, orienting, and executive systems. In feedback trials, children received feedback about their accuracy, whereas in the no-feedback trials, feedback was not given. In both conditions, children with ADHD performed more slowly than did typically developing children. They also showed impairments in the ability to disengage attention and in executive functioning, which improved when alertness was increased by administering the auditory warning. The performance of the attentional networks appeared to be modulated by the absence or the presence of reinforcement. We suggest that the observed executive system deficit in children with ADHD could depend on their low level of arousal rather than being an independent disorder. PMID- 22071485 TI - [Hospital emergencies and the prison population]. PMID- 22071486 TI - [Assessment of health benefits from a nutrition program aimed at inmates with cardiovascular risk factors at Huelva Prison]. AB - BACKGROUND: Diet and lifestyle are important factors in improving cardiovascular health and preventing chronic diseases. OBJECTIVES: Assessment of changes brought about in cardiovascular risk (CVR) and metabolic syndrome (MS) after inclusion in a nutritional program. MATERIALS AND METHODS: Intervention, nonrandomized prospective cohort study carried out at Huelva prison in a one year period. Information about quarterly and bi-annual anthropometric and blood biochemical variables was obtained to assess changes in diet. A descriptive analysis with LC 95% and pre-post study was also completed, using T-Student quantitative variables and Wilcoxon test averages. Qualitative testing was performed using the Chi square test. RESULTS: The sample consisted of 139 subjects, 44 patients were lost in the follow-up study and 95 completed the program. Diet modification took place in 86.3% of the cases. We obtained significant improvements in weight, body mass, fat mass, abdominal perimeter and diastolic blood pressure rate index variables (Table 3). We see a reduction in high and low CVR vs. medium CVR according to features of Framingham and REGICOR (without significance), remaining stable in the SCORE model (Table 4). CONCLUSIONS: Health education and proper diet improved anthropometric and biochemical parameters in these patients. This may imply a new tool in the health care repertoire that can be applied to other centres. PMID- 22071487 TI - [Infection by human papilloma virus amongst female inmates in a social re adaptation centre in South-West Mexico]. AB - INTRODUCTION: The aim of this work is describe the epidemiology of HVP amongst female inmates. MATERIAL AND METHODS: A total of 82 women were studied in a cross sectional study. Epidemiological data were collected through a direct interview. Samples of cervical cells were taken. HPV and genotypes were identified by molecular test. RESULTS: Global HPV prevalence was 20.7%. Fifteen different genotypes were identified 60% low risk HPV, 26.7% high risk HPV and 13.3% were not classified in any of the two groups. Types 6/11 were the most common. 23.5% (04/17) of HPV positives samples had multiple infections, 3 with 2 genotypes and one with 3. Association between infection with HPV and smoking was found, p= 0.0258, OR 3.79 IC 95% (1.01-15.58). PMID- 22071488 TI - [Psychologica well-being, perceived organizational support and job satisfaction amongst Chilean prison employees]. AB - This research aims to identify the relationship between job satisfaction, psychological well-being and Perceived Organizational Support amongst prison officials. 190 officials working in one state prison and one privately-run prison were evaluated using the Job Satisfaction Questionnaire1, Psychological Well being Scale2 and Scale of Perceived Organizational Support3. The main results show a significant positive correlation between job satisfaction, psychological well-being and perceived organizational support, so that those who are satisfied with their jobs tend to feel better psychologically and perceive that they receive support from their organizations. Furthermore the study variables showed no significant differences between officials at both prisons. As regards socio demographic figures, gender differences were found in terms of job satisfaction and psychological well-being, while no differences were found according to unit. PMID- 22071489 TI - [Health care strategies for mental health problems in the prison environment, the Spanish case in a European context]. AB - INTRODUCTION: A review was carried out of scientific literature on health care strategies for mental health problems in the prison environment. Data is given about the main activities put into practice by prison administrations as a response to the worrying information that has come to light in recent epidemiological studies on mental disorders in prison, with figures that, when compared to the general population, give results of double the number of cases of Common Mental Illness (CMI) and four times the number of cases of Severe Mental Illness (SMI) amongst prison inmates. MATERIALS AND METHODS: A review was made of the most important bibliographical databases containing health care policies for mental health problems in prison published by prison administrations in the last 10 years. This information was completed with other data obtained from an analysis of the indicators available in Health Care Coordination on its health care strategies for mental health in centres run by the Secretary General of Prisons, in Spain. RESULTS: There is little in the way of scientific literature that clearly states health care policies for mental illness in the prison environment. Those that do tend to agree with a number of affirmations that include the obligation to offer a therapeutic response of equal quality to that received by patients in the community, the need for a multi-disciplinary team responsible for caring for this type of patient, along with a coordinated effort between the medical, social, legal and prison administrations that at a given time have to care for them. PMID- 22071490 TI - [Giant hairy congenital pigmented nevus]. PMID- 22071491 TI - [Letter to the director from D. Julio Garcia-Guerrero and d. Enrique J. Vera Remartinez]. PMID- 22071492 TI - [Integration of prison health care]. PMID- 22071495 TI - Quantitative force and dissipation measurements in liquids using piezo-excited atomic force microscopy: a unifying theory. AB - The use of a piezoelectric element (acoustic excitation) to vibrate the base of microcantilevers is a popular method for dynamic atomic force microscopy. In air or vacuum, the base motion is so small (relative to tip motion) that it can be neglected. However, in liquid environments the base motion can be large and cannot be neglected. Yet it cannot be directly observed in most AFMs. Therefore, in liquids, quantitative force and energy dissipation spectroscopy with acoustic AFM relies on theoretical formulae and models to estimate the magnitude of the base motion. However, such formulae can be inaccurate due to several effects. For example, a significant component of the piezo excitation does not mechanically excite the cantilever but rather transmits acoustic waves through the surrounding liquid, which in turn indirectly excites the cantilever. Moreover, resonances of the piezo, chip and holder can obscure the true cantilever dynamics even in well designed liquid cells. Although some groups have tried to overcome these limitations (either by theory modification or better design of piezos and liquid cells), it is generally accepted that acoustic excitation is unsuitable for quantitative force and dissipation spectroscopy in liquids. In this paper the authors present a careful study of the base motion and excitation forces and propose a method by which quantitative analysis is in fact possible, thus opening this popular method for quantitative force and dissipation spectroscopy using dynamic AFM in liquids. This method is validated by experiments in water on mica using a scanning laser Doppler vibrometer, which can measure the actual base motion. Finally, the method is demonstrated by using small-amplitude dynamic AFM to extract the force gradients and dissipation on solvation shells of octamethylcyclotetrasiloxane (OMCTS) molecules on mica. PMID- 22071496 TI - Clinical recommendation for treatment planning of sinus augmentation procedures by using presurgical CAT scan images: a preliminary report. AB - PURPOSE: To propose a clinical recommendation based on anatomy of maxillary sinus before sinus augmentation procedure using presurgical computerized axial tomography (CAT) scan images. MATERIALS AND METHODS: CAT scan images were randomly selected from previous completed implant cases. Proposed area for the lateral window osteotomy was outlined on the panorex image of the CAT scan. Sagittal section on the CAT scan that was in the center of the outlined window was selected for sinus measurement analysis. On CAT scan, 2 lines were drawn to measure the dimensions of sinus. One line measured the horizontal width and the other line measured the vertical height. RESULTS: Based on the measurement data, a classification of the maxillary sinus anatomy was proposed. Narrow sinus cavity indicates favorable type anatomy in terms of bone regeneration healing and wide sinus cavity as less favorable anatomy for patient treatment planning. CONCLUSION: A narrow sinus and greater exposure to the blood supply should require shorter healing times after grafting. Conversely, wider sinus cavities and less exposure to the blood supply would require a longer healing time before implant placement. PMID- 22071497 TI - Bone-added osteotome technique versus lateral approach for sinus floor elevation: a comparative radiographic study. AB - PURPOSE: The aim of this study was to evaluate and compare the radiographic results of bone-added osteotome sinus floor elevation (BAOSFE) and lateral approach sinus floor elevation techniques. METHODS: The 43 patients who had undergone implant procedure with either BAOSFE or lateral approach method on their maxillary molar edentulous area were included. Their dental records were confirmative and the radiographic-changes using orthopantomographs were consistently checked up during 2 years after the procedure (immediately after procedure and 6 months, 12 months, and 24 months after implant placement). RESULTS: The radiographic evaluation after 2 years of implantation with sinus elevation showed the significant amount of bone formation (6.75 mm for BAOSFE and 11.36 mm for lateral approach method). Largest amount of grafted height loss occurred during the first 6 months (62.8% of total amount of bone loss), but the resorption was minimal (1.35 mm for BAOSFE and 1.36 mm for lateral approach method) for overall 24 months. CONCLUSION: Long-term stability of graft height was achieved using both BAOSFE and lateral approach sinus floor elevation. Overall, graft height decreased gradually during 2 years after procedures, but the changes were minimal. PMID- 22071498 TI - Treatment of severe sinus infection after sinus lift procedure: a case report. AB - Maxillary sinus floor augmentation may have a variety of postoperative complications including infection, sequestration of bone, and maxillary sinusitis. Complications can also occur due to a preexisting sinus condition called ostium stenosis. This case report presents a complication after sinus lift and grafting procedure due to an unrecognized ostium stenosis. CASE REPORT: A 50 year-old male patient had sinus augmentation on his right side. However, postoperatively, his symptoms were protracted. A CT scan showed thickening of the Schneiderian membrane and scattered graft material. Management included endoscopic nasal examination and ostium enlargement, antibiotic coverage, and full enucleation of the graft and diseased tissue. CONCLUSION: Patency of the sinus ostium should be carefully evaluated before sinus lift/grafting procedure using CT technology. Radiology and otolaryngology consultations may be necessary to rule out ostium stenosis before surgery. PMID- 22071500 TI - The association of plasma free amino acids with liver enzymes in Type 2 diabetic patients. AB - BACKGROUND: Elevated gamma-glutamyl transpeptidase (GGT) and alanine aminotransferase (ALT) could predict the risk of Type 2 diabetes (T2D), but the reason for their elevation was unclear. GGT and ALT mediated the metabolism of many amino acids (AA). Up to now, it was not investigated whether abnormal AA concentration was associated with elevated liver enzymes. AIM: This study was to investigate the status of AA in T2D and their relationship with liver enzymes. SUBJECTS AND METHODS: A total of 132 T2D patients and 137 healthy controls were recruited. Plasma free AA were measured by high-performance liquid chromatography. The contribution of individual AA to liver enzymes was assessed by stepwise linear regression. RESULTS: a) The levels of alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, methionine, glutamate, and lysine were higher while the level of glycine was lower in T2D than in controls (all p<0.01). b) Glutamate contributed to GGT in T2D, and its contribution was even greater than that of waist circumference. Leucine, lysine, and glutamate contributed to ALT. CONCLUSION: There were significant differences in plasma AA profile between T2D and controls. Abnormal AA might contribute to elevated liver enzymes. The interaction between AA, liver enzymes, and the risk of T2D should be further investigated by prospective studies. PMID- 22071501 TI - Conservative treatment with spontaneous stabilization of Grade II isthmic spondylolisthesis L5/S1 in a forty-four-year old woman, with a six-year follow up: a case report. AB - Spondylolisthesis is a pathological condition caused by the slipping of a vertebral body, compared to the underlying structure, following structural and/or degenerative changes to the spine. Studies have attempted evidence to the connection between the natural history of spondylolisthesis, the degree and progression of the slip factor, as well as the pain and disability. Studies have reported a high level of heterogeneity of these factors in different patients as well as difficulty in predicting behaviour. It has been suggested that vertebral instability, independent of the slip factor, could be considered the most important factor to be treated conservatively or surgically. Furthermore, it appears that some patients may manifest complete disk degeneration over time, with vertebral bodies shifting closer and spontaneous stabilisation. This case study reports a forty-four-year old woman, with isthmic spondylolisthesis, where the spine surgeon recommended physiotherapy for conservative treatment, with a prognosis of possible spontaneous stabilization. The case was followed for six years, both clinically and radiologically. Treatment was based on a specific stabilising training program (motor control), immediately aimed to improve the disability and pain factors while waiting for a possible spontaneous stabilisation, that the latest radiological exams revealed with an attempt of arthrodesis. The Oswestry Disability Index (ODI) and the Roland Morris Disability Questionnaire (RMDQ) to measure disability, and the Numeric Rating Scale (NRS) to measure pain, were carried out at the beginning, during and at the end of treatment. They were compared with the radiographic material documenting the evolution of the spondylolisthesis over time. This case study appears to confirm that the hypothesis that a specific aimed approach of rehabilitation may improve the disability and pain levels without compromising the process of spontaneous arthrodesis. The evolution was documented radiographically and clinically over a six-year period. PMID- 22071502 TI - The effect of variable practice on wheelchair propulsive efficiency and propulsive timing. AB - AIM: The net mechanical efficiency of wheelchair propulsion is very low, approximately 13%. It is necessary to look for effective practice methods to obtain greater output with less energy expenditure during wheelchair propulsions. Literature indicates that variable practice (VP) is more effective than constant practice (CP) in motor-skill learning. However, it is unknown if VP is more effective than CP in improving wheelchair propulsive efficiency. The purpose of the study was to determine how propulsive efficiency and propulsive timing were affected by variable practice and constant practice. DESIGN: This was an observational and experimental study. SETTING: The experiment was conducted in a well-controlled university research laboratory. POPULATION: A total of 33 able bodied subjects participated in this study. METHODS: Participants were randomly placed into one of the three training groups, two constant practice groups and one variable practice group. One constant group practiced wheelchair propulsion on a roller system with a single speed, 30% of the maximum speed, while the other constant group practiced using 55% of the maximum speed. The variable group practiced with both speeds. Three dependent variables, propulsive efficiency, timing, and intercycle variability of the timing, were measured. RESULTS: All groups improved the three dependent variables significantly after the training, and in general the VP group had greater improvement than the others in improving the propulsive efficiency. CONCLUSION: This study is the first to demonstrate the advantage of the VP over the CP in improving the propulsive efficiency. CLINICAL REHABILITATION IMPACT: This finding has great implication for paraplegics because they require greater workloads for upper-extremity activities. PMID- 22071504 TI - The importance of surface morphology in controlling the selectivity of polycrystalline copper for CO2 electroreduction. AB - This communication examines the effect of the surface morphology of polycrystalline copper on electroreduction of CO(2). We find that a copper nanoparticle covered electrode shows better selectivity towards hydrocarbons compared with the two other studied surfaces, an electropolished copper electrode and an argon sputtered copper electrode. Density functional theory calculations provide insight into the surface morphology effect. PMID- 22071503 TI - Combined therapeutic application of botulinum toxin type A, low-frequency rTMS, and intensive occupational therapy for post-stroke spastic upper limb hemiparesis. AB - BACKGROUND: For spastic upper limb hemiparesis after stroke, we developed triple element protocol of botulinum toxin type A (BoNTA) injection, low-frequency repetitive transcranial magnetic stimulation (LF-rTMS), and intensive occupational therapy (OT). Aim. To investigate the safety and feasibility of the protocol. Design. A preliminary study. Setting. At a university hospital. Population. Fourteen post-stroke patients with spastic upper limb hemiparesis (mean age: 54.9+/-9.2 years, time after onset: 87.1+/-48.2 months, +/-SD). METHODS: In all patients, BoNTA was injected into spastic muscles of the affected upper limb (maximum total dose: 240 units). Four weeks later, they were hospitalized to receive 22 sessions of 20-min LF-rTMS and 120-min intensive OT daily over 15 days. Motor function of the affected upper limb was evaluated mainly using Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), motor activity log (MAL), and the severity of spasticity was measured with modified Ashworth scale (MAS) at BoNTA injection, discharge and four weeks post-discharge. RESULTS: All patients completed the protocol without any adverse effects. The FMA score and MAL scores, but not WMFT performance time, improved significantly at discharge. The MAS score of all examined muscles decreased significantly between BoNTA and discharge. The beneficial effect of the protocol on motor function and spasticity was almost maintained until four weeks after discharge. CONCLUSION: The protocol is safe and feasible, although further larger studies are needed to confirm its efficacy. CLINICAL REHABILITATION IMPACT: The protocol is a potentially useful neurorehabilitative approach for this patient population. PMID- 22071505 TI - Toxic effects of amyloid fibrils on cell membranes: the importance of ganglioside GM1. AB - The interaction of amyloid aggregates with the cell plasma membrane is currently considered among the basic mechanisms of neuronal dysfunction in amyloid neurodegeneration. We used amyloid oligomers and fibrils grown from the yeast prion Sup35p, responsible for the specific prion trait [PSI(+)], to investigate how membrane lipids modulate fibril interaction with the membranes of cultured H END cells and cytotoxicity. Sup35p shares no homology with endogenous mammalian polypeptide chains. Thus, the generic toxicity of amyloids and the molecular events underlying cell degeneration can be investigated without interference with analogous polypeptides encoded by the cell genome. Sup35 fibrils bound to the cell membrane without increasing its permeability to Ca(2+). Fibril binding resulted in structural reorganization and aggregation of membrane rafts, with GM1 clustering and alteration of its mobility. Sup35 fibril binding was affected by GM1 or its sialic acid moiety, but not by cholesterol membrane content, with complete inhibition after treatment with fumonisin B1 or neuraminidase. Finally, cell impairment resulted from caspase-8 activation after Fas receptor translocation on fibril binding to the plasma membrane. Our observations suggest that amyloid fibrils induce abnormal accumulation and overstabilization of raft domains in the cell membrane and provide a reasonable, although not unique, mechanistic and molecular explanation for fibril toxicity. PMID- 22071506 TI - Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics. AB - Allostery offers a highly specific way to modulate protein function. Therefore, understanding this mechanism is of increasing interest for protein science and drug discovery. However, allosteric signal transmission is difficult to detect experimentally and to model because it is often mediated by local structural changes propagating along multiple pathways. To address this, we developed a method to identify communication pathways by an information-theoretical analysis of molecular dynamics simulations. Signal propagation was described as information exchange through a network of correlated local motions, modeled as transitions between canonical states of protein fragments. The method was used to describe allostery in two-component regulatory systems. In particular, the transmission from the allosteric site to the signaling surface of the receiver domain NtrC was shown to be mediated by a layer of hub residues. The location of hubs preferentially connected to the allosteric site was found in close agreement with key residues experimentally identified as involved in the signal transmission. The comparison with the networks of the homologues CheY and FixJ highlighted similarities in their dynamics. In particular, we showed that a preorganized network of fragment connections between the allosteric and functional sites exists already in the inactive state of all three proteins. PMID- 22071507 TI - Gender differences in cancer screening beliefs, behaviors, and willingness to participate: implications for health promotion. AB - Men have higher cancer mortality rates for all sites combined compared with women. Cancer screening (CS) participation is important for the early detection of cancer. This study explores gender differences in CS beliefs, behaviors, and willingness to participate. The data were collected from a stratified, random digit dial survey of adults living in New York, Maryland, and Puerto Rico. Chi square tests and logistic regressions were computed to analyze gender associations among CS beliefs, behaviors, and willingness variables. Men and women believed that CSs were effective, though a higher percentage of men had never had a past CS. Men were less willing to participate in a CS at the present time and in a skin cancer exam; however, when given descriptions of screening conditions, men indicated more willingness to participate. These gender differences highlight the need for health professionals to examine their efforts in providing enhanced CS promotion and education among men. PMID- 22071508 TI - The effect of sex and severity of aggression on formal and informal social agents' involvement in partner violence. AB - Involvement by formal and informal social agents plays a major role in coping with the problem of partner violence. Based on data from the First National Israeli Survey of Family Violence, the present study attempted to answer whether the sex of the aggressor and the severity of his or her aggression affect formal and informal social involvement in partner violence. Data were obtained from a stratified probability sample of 2,544 women drawn from the general population in Israel. Findings show that the severity of aggression by both sexes affects informal social involvement similarly. But in regard to formal involvement, gender is of top importance, and only the severity of men's aggression influences formal social involvement. The findings indicate society's perceptions of partner violence and how it copes with the problem. These perceptions and their theoretical and practical implications are discussed. The discussion focuses on examining the factors that promote social construction of partner violence as identified in this study and the implications of this construction on dealing with the problem. PMID- 22071509 TI - Examining the cross-reactivity and neutralization mechanisms of a panel of mAbs against adeno-associated virus serotypes 1 and 5. AB - Neutralizing antibodies play a central role in the prevention and clearance of viral infections, but can be detrimental to the use of viral capsids for gene delivery. Antibodies present a major hurdle for ongoing clinical trials using adeno-associated viruses (AAVs); however, relatively little is known about the antigenic epitopes of most AAV serotypes or the mechanism(s) of antibody-mediated neutralization. We developed panels of AAV mAbs by repeatedly immunizing mice with AAV serotype 1 (AAV1) capsids, or by sequentially immunizing with AAV1 followed by AAV5 capsids, in order to examine the efficiency and mechanisms of antibody-mediated neutralization. The antibodies were not cross-reactive between heterologous AAV serotypes except for a low level of recognition of AAV1 capsids by the AAV5 antibodies, probably due to the initial immunization with AAV1. The neutralization efficiency of different IgGs varied and Fab fragments derived from these antibodies were generally poorly neutralizing. The antibodies appeared to display various alternative mechanisms of neutralization, which included inhibition of receptor-binding and interference with a post-attachment step. PMID- 22071510 TI - Generation of T-cell receptors targeting a genetically stable and immunodominant cytotoxic T-lymphocyte epitope within hepatitis C virus non-structural protein 3. AB - Hepatitis C virus (HCV) is a major cause of severe liver disease, and one major contributing factor is thought to involve a dysfunction of virus-specific T cells. T-cell receptor (TCR) gene therapy with HCV-specific TCRs would increase the number of effector T-cells to promote virus clearance. We therefore took advantage of HLA-A2 transgenic mice to generate multiple TCR candidates against HCV using DNA vaccination followed by generation of stable T-cell-BW (T-BW) tumour hybrid cells. Using this approach, large numbers of non-structural protein 3 (NS3)-specific functional T-BW hybrids can be generated efficiently. These predominantly target the genetically stable HCV genotype 1 NS3(1073-1081) CTL epitope, frequently associated with clearance of HCV in humans. These T-BW hybrid clones recognized the NS3(1073) peptide with a high avidity. The hybridoma effectively recognized virus variants and targeted cells with low HLA-A2 expression, which has not been reported previously. Importantly, high-avidity murine TCRs effectively redirected human non-HCV-specific T-lymphocytes to recognize human hepatoma cells with HCV RNA replication driven by a subgenomic HCV replicon. Taken together, TCR candidates with a range of functional avidities, which can be used to study immune recognition of HCV-positive targets, have been generated. This has implications for TCR-related immunotherapy against HCV. PMID- 22071511 TI - Diversity of murine norovirus in wild-rodent populations: species-specific associations suggest an ancient divergence. AB - A survey of wild-rodent populations has revealed that murine norovirus (MNV) is present and diverse in wild-house mice Mus musculus. This virus is genetically similar to MNV infecting show mice and previously described variants circulating in laboratory mice. The detection of MNV in wild-mouse populations suggests that MNV infection of laboratory mice and show mice (from which laboratory mice are derived) derives from contact with or their origins from wild-mouse progenitors. The survey additionally identified frequent infection of wood mice (Apodemus sylvaticus) with genetically divergent variants of MNV. These viruses are distinct from previously described MNV variants, differing by 22-23 % over the complete genome sequence compared with a maximum of 13 % between M. musculus derived strains. Comparison with other noroviruses reveals that the Apodemus MNV groups with MNV in genogroup V and shares the same overall genome organization, predicted lengths of proteins encoded by ORFs 1-3 and the existence of a conserved alternative reading frame in VP1 encoding a homologue of the MNV ORF4. Different Apodemus MNV isolates were as variable as MNV isolates and showed evidence for inter-isolate recombination. Our observation of species-specific associations of MNV variants in wild populations suggests that murine noroviruses have an ancient origin, a feature that they may share with other norovirus genogroups. PMID- 22071512 TI - JC virus promoter/enhancers contain TATA box-associated Spi-B-binding sites that support early viral gene expression in primary astrocytes. AB - JC virus (JCV) is the aetiological agent of the demyelinating disease progressive multifocal leukoencephalopathy, an AIDS defining illness and serious complication of mAb therapies. Initial infection probably occurs in childhood. In the working model of dissemination, virus persists in the kidney and lymphoid tissues until immune suppression/modulation causes reactivation and trafficking to the brain where JCV replicates in oligodendrocytes. JCV infection is regulated through binding of host factors such as Spi-B to, and sequence variation in the non coding control region (NCCR). Although NCCR sequences differ between sites of persistence and pathogenesis, evidence suggests that the virus that initiates infection in the brain disseminates via B-cells derived from latently infected haematopoietic precursors in the bone marrow. Spi-B binds adjacent to TATA boxes in the promoter/enhancer of the PML-associated JCV Mad-1 and Mad-4 viruses but not the non-pathogenic, kidney-associated archetype. The Spi-B-binding site of Mad-1/Mad-4 differs from that of archetype by a single nucleotide, AAAAGGGAAGGGA to AAAAGGGAAGGTA. Point mutation of the Mad-1 Spi-B site reduced early viral protein large T-antigen expression by up to fourfold. Strikingly, the reverse mutation in the archetype NCCR increased large T-antigen expression by 10-fold. Interestingly, Spi-B protein binds the NCCR sequence flanking the viral promoter/enhancer, but these sites are not essential for early viral gene expression. The effect of mutating Spi-B-binding sites within the JCV promoter/enhancer on early viral gene expression strongly suggests a role for Spi B binding to the viral promoter/enhancer in the activation of early viral gene expression. PMID- 22071513 TI - The evolutionary rate of citrus tristeza virus ranks among the rates of the slowest RNA viruses. AB - Citrus tristeza virus (CTV) has been studied intensively at the molecular level. However, knowledge regarding the dynamics of its evolution is practically non existent. In the past, diverse authors have referred to CTV as a highly variable virus, implying rapid evolution. Others have, in recent times, referred to CTV as an exceptionally slowly evolving virus. In this work, we used the capsid protein (CP) gene to estimate the rate of evolution. This was obtained from a large set of heterochronous CP gene sequences using a bayesian coalescent approach. The best-fitting evolutionary and population models pointed to an evolutionary rate of 1.58*10(-4) nt per site year(-1) (95 % highest posterior density, 1.73*10(-5) 3.16*10(-4) nt per site year(-1)). For an unbiased comparison with other plant and animal viruses, the evolutionary rate of synonymous substitutions was considered. In a series of 88 synonymous evolutionary rates, ranging from 5.2*10( 6) to 6.2*10(-2) nt per site year(-1), CTV ranks in the 10th percentile, embedded among the slowest animal RNA viruses. At the time of citrus dissemination to Europe and the New World, the major clades that led to the current phylogenetic groups were already defined, which may explain the absence nowadays of geographical speciation. PMID- 22071514 TI - Identification of a novel single-stranded, circular DNA virus from bovine stool. AB - We report the identification of a novel single-stranded, circular DNA virus isolated from bovine stool. The virus, named bovine stool-associated circular DNA virus (BoSCV), has a genome comprising 2600 bases of circular ssDNA, with two putative ORFs encoding replicase and capsid proteins, arranged inversely. The stem-loop structure was located between the 3' ends of the two putative ORFs, as in chimpanzee stool-associated circular virus (ChimpSCV) and unlike other circular DNA viruses, including members of the families Circoviridae, Nanoviridae and Geminiviridae. BoSCV was also genetically similar to ChimpSCV, with approximately 30 % identity in the replicase and capsid proteins. A phylogenetic analysis based on the replicase protein showed that BoSCV and ChimpSCV are in the same clade. A field survey using BoSCV-specific PCRs targeting ORF1 detected BoSCV and BoSCV-like sequences in bovine and porcine stool samples. BoSCV appears to belong to a new genus of circular DNA viruses. PMID- 22071515 TI - Tax1-expressing feline 8C cells are useful to monitor the life cycle of human T cell leukemia virus type I. AB - Extremely low infectivity has hampered direct (cell-free) infection studies of human T-cell leukemia virus type I (HTLV-I). In order to break through this barrier, we examined the susceptibility of many kinds of cells to HTLV-I and found a feline kidney cell line, 8C, that is highly susceptible to HTLV-I and produced remarkable amounts of infectious progeny viruses. Tax1 protein encoded by HTLV-I is known as a transcription activator for viral and cellular genes. We found that the 8C cells expressing the Tax1 protein (8C/TaxWT cells) can produce more progeny viruses than 8C cells when the cells were exposed to cell-free HTLV I. A large number of syncytia were also induced in these cells. Here, we propose 8C/TaxWT cells as a useful tool to study the cell-free HTLV-I infection. PMID- 22071516 TI - Synthesis and electrocatalytic activity of Au/Pt bimetallic nanodendrites for ethanol oxidation in alkaline medium. AB - Gold/Platinum (Au/Pt) bimetallic nanodendrites were successfully synthesized through seeded growth method using preformed Au nanodendrites as seeds and ascorbic acid as reductant. Cyclic voltammograms (CVs) of a series of Au/Pt nanodendrites modified electrodes in 1M KOH solution containing 1M ethanol showed that the electrocatalyst with a molar ratio (Au:Pt) of 3 exhibited the highest peak current density and the lowest onset potential. The peak current density of ethanol electro-oxidation on the Au(3)Pt(1) nanodendrites modified glassy carbon electrode (Au(3)Pt(1) electrode) is about 16, 12.5, and 4.5 times higher than those on the polycrystalline Pt electrode, polycrystalline Au electrode, and Au nanodendrites modified glassy carbon electrode (Au dendrites electrode), respectively. The oxidation peak potential of ethanol electro-oxidation on the Au(3)Pt(1) electrode is about 299 and 276 mV lower than those on the polycrystalline Au electrode and Au dendrites electrode, respectively. These results demonstrated that the Au/Pt bimetallic nanodendrites may find potential application in alkaline direct ethanol fuel cells (ADEFCs). PMID- 22071517 TI - Enhancement of DNA compaction by negatively charged nanoparticles: effect of nanoparticle size and surfactant chain length. AB - We study the compaction of genomic DNA by a series of alkyltrimethylammonium bromide surfactants having different hydrocarbon chain lengths n: dodecyl-(DTAB, n=12), tetradecyl-(TTAB, n=14) and hexadecyl-(CTAB, n=16), in the absence and in the presence of negatively charged silica nanoparticles (NPs) with a diameter in the range 15-100 nm. We show that NPs greatly enhance the ability of all cationic surfactants to induce DNA compaction and that this enhancement increases with an increase in NP diameter. In the absence of NP, the ability of cationic surfactants to induce DNA compaction increases with an increase in n. Conversely, in the presence of NPs, the enhancement of DNA compaction increases with a decrease in n. Therefore, although CTAB is the most efficient surfactant to compact DNA, maximal enhancement by NPs is obtained for the largest NP diameter (here, 100 nm) and the smallest surfactant chain length (here, DTAB). We suggest a mechanism where the preaggregation of surfactants on NP surface mediated by electrostatic interactions promotes cooperative binding to DNA and thus enhances the ability of surfactants to compact DNA. We show that the amplitude of enhancement is correlated with the difference between the surfactant concentration corresponding to aggregation on DNA alone and that corresponding to the onset of adsorption on nanoparticles. PMID- 22071518 TI - Transparent polymeric hybrid film of ZnO nanoparticle quantum dots and PMMA with high luminescence and tunable emission color. AB - ZnO nanoparticle quantum dots (QDs)/poly(methyl methacrylate) (PMMA) composites are synthesized by conventional radical polymerization in the presence of 3 (trimethoxysilyl)propylmethacrylate (TPM)-modified ZnO nanoparticle QDs. Although unmodified ZnO nanoparticle QDs were precipitated in tetrahydrofuran (THF) and show only weak emissions under UV irradiation, ZnO nanoparticle QDs/PMMA composite is well dispersed in THF and shows high emissions. TPM acts as the stabilizer and promotes the compatibility between the ZnO nanoparticle QDs and the PMMA matrix. After evaporation of THF from the ZnO nanoparticle QDs/PMMA composite solution, transparent polymeric hybrid films of ZnO nanoparticle QDs and PMMA are obtained. These polymeric hybrid films are characterized by photoluminescence (PL) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and thermogravimetric analysis. The hybrid film exhibited a high quantum yield and PL emission under ultraviolet excitation. PL emission has been successfully tuned from blue to yellow. PMID- 22071519 TI - Squaramide-catalyzed enantioselective Michael addition of malononitrile to chalcones. AB - A highly enantioselective Michael addition of malononitrile to chalcones catalyzed by a chiral quinine-derived squaramide catalyst has been developed. This organocatalytic reaction at a very low catalyst loading (0.5 mol%) led to chiral gamma-cyano carbonyl compounds in good yields with high enantioselectivities (up to 96% ee) under mild reaction conditions. PMID- 22071520 TI - Cosmomycin C inhibits signal transducer and activator of transcription 3 (STAT3) pathways in MDA-MB-468 breast cancer cell. AB - The signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer cells. Therefore, blocking the aberrant activity of STAT3 in tumor cells is a validated therapeutic strategy. To discover novel inhibitors of STAT3 activity, we screened against microbial natural products using a dual luciferase assay. Using the microbial metabolome library, we identified cosmomycin C (CosC), which was isolated from the mycelium extract of Streptomyces sp. KCTC19769, as a STAT3 pathway inhibitor. CosC inhibited STAT3 (Tyr705) phosphorylation and subsequent nuclear translocation in MDA-MB-468 breast cancer cells. CosC-mediated inhibition of STAT3 signaling pathway was confirmed by suppressed expression of STAT3 downstream target proteins including cyclin D1, Bcl-xL, survivin, Mcl-1, and VEGF in CosC-treated MDA-MB-468 cells. Flow cytometry showed that CosC caused accumulation in the G(0)-G(1) phase of the cell cycle and induced apoptosis via PARP cleavage and caspase-3 activation. Based on these findings, CosC may be a potential candidate for modulation of STAT3 pathway. PMID- 22071521 TI - Camptothecin (CPT) directly binds to human heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and inhibits the hnRNP A1/topoisomerase I interaction. AB - Camptothecin (CPT) is an anti-tumor natural product that forms a ternary complex with topoisomerase I (top I) and DNA (CPT-top I-DNA). In this study, we identified the direct interaction between CPT and human heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) using the T7 phage display technology. On an avidin-agarose bead pull down assay, hnRNP A1 protein was selectively pulled down in the presence of C20-biotinylated CPT derivative (CPT-20-B) both in vitro and in vivo. The interaction was also confirmed by an analysis on a quartz-crystal microbalance (QCM) device, yielding a K(D) value of 82.7 nM. A surface plasmon resonance (SPR) analysis revealed that CPT inhibits the binding of hnRNP A1 to top I (K(D): 260 nM) in a non-competitive manner. Moreover, an in vivo drug evaluation assay using Drosophila melanogaster showed that the knockout of the hnRNP A1 homolog Hrb87F gene showed high susceptibility against 5-50 MUM of CPT as compared to a wild-type strain. Such susceptibility was specific for CPT and not observed after treatment with other cytotoxic drugs. Collectively, our data suggests that CPT directly binds to hnRNP A1 and non-competitively inhibits the hnRNP A1/top I interaction in vivo. The knockout strain loses the hnRNP A1 homolog as a both CPT-binding partner and naive brakes of top I, which enhances the formation of the CPT-top I-DNA ternary complexes and subsequently sensitizes the growth inhibitory effect of CPT in D. melanogaster. PMID- 22071522 TI - Aza vinyl sulfones: synthesis and evaluation as antiplasmodial agents. AB - A series of novel aza vinyl sulfones were designed, synthesized in good yields and evaluated as antiplasmodial agents. Tested compounds did not show activity against papain or the Plasmodium falciparum cysteine protease falcipain-2. However, a number of the new compounds effectively inhibited the in vitro development of P. falciparum. Compounds containing a squaramide group were the most active, with IC(50) values between 0.95 and 4.5 MUM, suggesting that these are potential lead compounds for the development of new antimalarial agents. PMID- 22071523 TI - Triterpenoids as inhibitors of erythrocytic and liver stages of Plasmodium infections. AB - Bioassay-guided fractionation of the methanol extract of Momordica balsamina led to the isolation of two new cucurbitane-type triterpenoids, balsaminol F (1) and balsaminoside B (2), along with the known glycosylated cucurbitacins, cucurbita 5,24-diene-3beta,23(R)-diol-7-O-beta-D-glucopyranoside (3) and kuguaglycoside A (4). Compound 1 was acylated yielding two new triesters, triacetylbalsaminol F (5) and tribenzoylbalsaminol F (6). The structures were elucidated based on spectroscopic methods including 2D-NMR experiments (COSY, HMQC, HMBC and NOESY). Compounds 1-6, were evaluated for their antimalarial activity against the erythrocytic stages of the Plasmodium falciparum chloroquine-sensitive strain 3D7 and the chloroquine-resistant clone Dd2. Assessment of compounds (1-3 and 5, 6) activity against the liver stage of Plasmodium berghei was also performed, measuring the luminescence intensity in Huh-7 cells infected with a firefly luciferase-expressing P. berghei line, PbGFP-Luc(con). Active compounds were shown to inhibit the parasite's intracellular development rather than its ability to invade hepatic cells. Toxicity of compounds (1-3 and 5, 6) was assessed on the same cell line and on mouse primary hepatocytes through the fluorescence measurement of cell confluency. Furthermore, toxicity of compounds 1-6 towards human cells was also investigated in the MCF-7 breast cancer cell line, showing that they were not toxic or exhibited weak toxicity. In blood stages of P. falciparum, compounds 1-5 displayed antimalarial activity, revealing triacetylbalsaminol F (5) the highest antiplasmodial effects (IC(50) values: 0.4MUM, 3D7; 0.2MUM, Dd2). The highest antiplasmodial activity against the liver stages of P.berghei was also displayed by compound 5, with high inhibitory activity and no toxicity. PMID- 22071524 TI - Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4 naphthoquinone: evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO. AB - Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic and exogenous amines and its inhibitors have therapeutic value for several conditions including affective disorders, stroke, neurodegenerative diseases and aging. The discovery of 2,3,6-trimethyl-1,4-naphthoquinone (TMN) as a nonselective and reversible inhibitor of MAO, has suggested 1,4-naphthoquinone (1,4-NQ) as a potential scaffold for designing new MAO inhibitors. Combining molecular modeling tools and biochemical assays we evaluate the kinetic and molecular details of the inhibition of human MAO by 1,4-NQ, comparing it with TMN and menadione. Menadione (2-methyl-1,4-naphthoquinone) is a multitarget drug that acts as a precursor of vitamin K and an inducer of mitochondrial permeability transition. Herein we show that MAO-B was inhibited competitively by 1,4-NQ (K(i)=1.4 MUM) whereas MAO-A was inhibited by non-competitive mechanism (K(i)=7.7 MUM). Contrasting with TMN and 1,4-NQ, menadione exhibited a 60-fold selectivity for MAO-B (K(i)=0.4 MUM) in comparison with MAO-A (K(i)=26 MUM), which makes it as selective as rasagiline. Fluorescence and molecular modeling data indicated that these inhibitors interact with the flavin moiety at the active site of the enzyme. Additionally, docking studies suggest the phenyl side groups of Tyr407 and Tyr444 (for MAO-A) or Tyr398 and Tyr435 (for MAO-B) play an important role in the interaction of the enzyme with 1,4-NQ scaffold through forces of dispersion as verified for menadione, TMN and 1,4-NQ. Taken together, our findings reveal the molecular details of MAO inhibition by 1,4-NQ scaffold and show for the first time that menadione acts as a competitive and reversible inhibitor of human MAO. PMID- 22071525 TI - Recent advances in the biology and chemistry of the flavaglines. AB - The flavaglines are a family of plant natural products that induce potent anticancer and neuroprotective activities. This review summarizes recent synthetic approaches to flavaglines and the current status of their pharmacological properties. PMID- 22071526 TI - Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation. AB - A series of compounds designed to adopt a conformation similar to the tubulin binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling beta-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed moderate to good cytotoxicity. PMID- 22071527 TI - Synthesis, structure-activity relationships, and mechanism of action of anti-HIV 1 lamellarin alpha 20-sulfate analogues. AB - Lamellarin alpha and six different types of lamellarin alpha 20-sulfate analogues were synthesized and their structure-activity relationships were investigated using a single round HIV-1 vector infection assay. All lamellarin sulfates having pentacyclic lamellarin core exhibited anti-HIV-1 activity at a 10 MUM concentration range regardless of the number and position of the sulfate group. On the other hand, non-sulfated lamellarin alpha and ring-opened lamellarin sulfate analogues did not affect HIV-1 vector infection in similar concentrations. The lamellarin sulfates utilized in this study did not exhibit unfavorable cytotoxic effect under the concentrations tested (IC(50)>100 MUM). Confocal laser scanning microscopic analysis indicated that hydrophilic lamellarin sulfates were hardly incorporated in the cell. HIV-1 Env-mediated cell cell fusion was suppressed by lamellarin sulfates. These results suggested that lamellarin sulfates have a novel anti-HIV-1 activity besides the previously reported integrase activity inhibition, possibly at a viral entry step of HIV-1 replication. PMID- 22071528 TI - The impact of electronic health records on care of heart failure patients in the emergency room. AB - OBJECTIVE: To evaluate if electronic health records (EHR) have observable effects on care outcomes, we examined quality and efficiency measures for patients presenting to emergency departments (ED). MATERIALS AND METHODS: We conducted a retrospective study of 5166 adults with heart failure in three metropolitan EDs. Patients were termed internal if prior information was in the EHR upon ED presentation, otherwise external. Associations of internality with hospitalization, mortality, length of stay (LOS), and numbers of tests, procedures, and medications ordered in the ED were examined after adjusting for age, gender, race, marital status, comorbidities and hospitalization as a proxy for acuity level where appropriate. RESULTS: At two EDs internals had lower odds of mortality if hospitalized (OR 0.55; 95% CI 0.38 to 0.81 and 0.45; 0.21 to 0.96), fewer laboratory tests during the ED visit (-4.6%; -8.9% to -0.1% and 14.0%; -19.5% to -8.1%) as well as fewer medications (-33.6%; -38.4% to -28.4% and -21.3%; -33.2% to -7.3%). At one of these two EDs, internals had lower odds of hospitalization (0.37; 0.22 to 0.60). At the third ED, internal patients only experienced a prolonged ED LOS (32.3%; 6.3% to 64.8%) but no other differences. There was no association with hospital LOS or number of procedures ordered. DISCUSSION: EHR availability was associated with salutary outcomes in two of three ED settings and prolongation of ED LOS at a third, but evidence was mixed and causality remains to be determined. CONCLUSIONS: An EHR may have the potential to be a valuable adjunct in the care of heart failure patients. PMID- 22071529 TI - Detecting pregnancy use of non-hormonal category X medications in electronic medical records. AB - OBJECTIVES: To determine whether a rule-based algorithm applied to an outpatient electronic medical record (EMR) can identify patients who are pregnant and prescribed medications proved to cause birth defects. DESIGN: A descriptive study using the University of Pennsylvania Health System outpatient EMR to simulate a prospective algorithm to identify exposures during pregnancy to category X medications, soon enough to intervene and potentially prevent the exposure. A subsequent post-hoc algorithm was also tested, working backwards from pregnancy endpoints, to search for possible exposures that should have been detected. MEASUREMENTS: Category X medications prescribed to pregnant patients. RESULTS: The alert simulation identified 2201 pregnancies with 16,969 pregnancy months (excluding abortions and ectopic pregnancies). Of these, 30 appeared to have an order for a non-hormone category X medication during pregnancy. However, none of the 30 'exposed pregnancies' were confirmed as true exposures in medical records review. The post-hoc algorithm identified 5841 pregnancies with 64 exposed pregnancies in 52,569 risk months, only one of which was a confirmed case. CONCLUSIONS: Category X medications may indeed be used in pregnancy, although rarely. However, most patients identified by the algorithm as exposed in pregnancy were not truly exposed. Therefore, implementing an electronic warning without evaluation would have inconvenienced prescribers, possibly hurting some patients (leading to non-use of needed drugs), with no benefit. These data demonstrate that computerized physician order entry interventions should be selected and evaluated carefully even before their use, using alert simulations such as that performed here, rather than just taken off the shelf and accepted as credible without formal evaluation. PMID- 22071530 TI - Patient reported barriers to enrolling in a patient portal. AB - BACKGROUND: Previous studies of patient portals have found low rates of enrollment and significant disparities in enrollment by race and ethnicity. As the reasons for these findings are unclear, we sought to identify patient reported barriers to enrollment in a patient portal. METHODS: We conducted a telephone survey of patients in one urban general internal medicine clinic. Patients were eligible if they did not enroll within 30 days of receiving an electronic order inviting participation. Our primary outcomes were: (a) reasons for not enrolling in the patient portal; (b) reasons for not attempting enrollment; and (c) perceived benefits of the portal. RESULTS: Participants' (N=159) mean age was 51 years, 48% were black, 72% female, and 70% had a college degree or greater. 63% of respondents not enrolling reported never attempting enrollment despite remembering receiving an order. Most of these 63% did not attempt enrollment because of lack of information or motivation. Smaller proportions reported not attempting enrollment because of negative attitudes toward the portal (30%) or computer related obstacles (8%). Overall, respondents favorably viewed most patient portal features, however black respondents were less likely than white respondents to consider features assisting self-management such as getting test results (69% vs 86%; p<0.05) as important. Adjusting for age, gender, education, and chronic disease did not substantially change results. CONCLUSION: Strategies to increase enrollment in patient portals need to ensure patients understand patient portal features and receive follow-up reminders. Interventions to reduce racial disparities in enrollment must address attitudinal barriers and not focus solely on improving access. PMID- 22071531 TI - The Hub Population Health System: distributed ad hoc queries and alerts. AB - The Hub Population Health System enables the creation and distribution of queries for aggregate count information, clinical decision support alerts at the point-of care for patients who meet specified conditions, and secure messages sent directly to provider electronic health record (EHR) inboxes. Using a metronidazole medication recall, the New York City Department of Health was able to determine the number of affected patients and message providers, and distribute an alert to participating practices. As of September 2011, the system is live in 400 practices and within a year will have over 532 practices with 2500 providers, representing over 2.5 million New Yorkers. The Hub can help public health experts to evaluate population health and quality improvement activities throughout the ambulatory care network. Multiple EHR vendors are building these features in partnership with the department's regional extension center in anticipation of new meaningful use requirements. PMID- 22071532 TI - What is the real effect of 1-Hz repetitive transcranial magnetic stimulation on hallucinations? Controlling for publication bias in neuromodulation trials. PMID- 22071533 TI - Ifenprodil for the treatment of flashbacks in female posttraumatic stress disorder patients with a history of childhood sexual abuse. PMID- 22071534 TI - Clinical snippets. PMID- 22071537 TI - Local actions of thyrotropin-releasing hormone regulate hair color. PMID- 22071538 TI - Toward the isolation and culture of melanocyte stem cells. AB - A new level of understanding of pigment cell biology and pathology will require the ability to culture and manipulate melanocyte stem cells (MCSCs) in vitro. In this issue, Nishikawa-Torikai et al. report progress toward this end. MCSCs isolated from mouse hair follicles can be expanded in vitro in a feeder-layer culture system. Application to human systems can be expected. PMID- 22071539 TI - Axl of evil? AB - Receptor tyrosine kinases (RTKs) play key roles in the initiation and progression of human skin cancers, yet the importance of some RTKs remains poorly understood. In this issue, Sensi et al. provide new insights into the expression and function of the RTK, Axl, in melanoma. The investigators show that Axl is frequently expressed in melanoma cell lines, particularly mutant NRAS-harboring lines, and that Axl activation by its ligand, Gas6, probably occurs via both autocrine and paracrine mechanisms. Gene signatures from Axl-expressing cell lines are similar to published signatures from poorly differentiated tumors displaying high metastatic potential. Functionally, Axl was required for the invasive and migratory properties of Axl-expressing melanoma cell lines. These data emphasize that targeting the Gas6-Axl signaling axis should be investigated as a strategy to inhibit prometastatic properties in poorly differentiated melanomas. PMID- 22071540 TI - Infantile hemangioma research: looking backward and forward. AB - This is a remarkable time to be a student of infantile hemangiomas (IHs). IH is a common tumor, estimated to occur in approximately 4% of infants. Studied for many decades, the acquisition of knowledge and pace of IH research are accelerating. The article by Greenberger et al. in this issue is a welcome addition to the literature. It examines rapamycin as a possible treatment for IH that could potentially be curative because suppression of self-renewal of stem cells might deplete hemangiomas of the stem cells from which they originate. However, before we get too enthusiastic about using rapamycin for IHs, it is important to reflect on lessons learned from previous hemangioma therapies. PMID- 22071543 TI - Mn monolayer modified Rh for syngas-to-ethanol conversion: a first-principles study. AB - Rh is unique in its ability to convert syngas to ethanol with the help of promoters. We performed systematic first-principles computations to examine the catalytic performance of pure and Mn modified Rh(100) surfaces for ethanol formation from syngas. CO dissociation on the surface as well as CO insertion between the chemisorbed CH(3) and the surface are the two key steps. The CO dissociation barrier on the Mn monolayer modified Rh(100) surface is remarkably lowered by ~1.5 eV compared to that on Rh(100). Moreover, the reaction barrier of CO insertion into the chemisorbed CH(3) group on the Mn monolayer modified Rh(100) surface is 0.34 eV lower than that of methane formation. Thus the present work provides new mechanistic insight into the role of Mn promoters in improving Rh's selectivity to convert syngas to ethanol. PMID- 22071550 TI - Transition to seizure in photosensitive epilepsy. AB - Photosensitive epilepsy (PSE) offers a highly reproducible model to investigate whether changes in neuronal activity preceding the transition to an epileptic photoparoxysmal response (PPR) may be detected. We investigated this possibility in patients with idiopathic PSE using MEG, as well as normal controls and non photosensitive epileptic patients of the same age group. Spectral analysis of the MEG signals recorded during intermittent light stimulation revealed relevant information in the phase spectrum. To quantify this effect, we introduced a second order response feature of the stimulus-triggered visual response preceding the PPR: the phase clustering index, which measures how close the phases of successive periods are grouped for each frequency component for all periods of the stimuli applied. We found that an enhancement of phase synchrony in the gamma band (30-120Hz), harmonically related to the frequency of stimulation, preceded the stimulation trials that evolved into PPRs, and differed significantly from that encountered in trials not followed by PPR or in control subjects. Thus this index can be considered a valuable index of the pro-ictal transition to seizures in photosensitive epilepsy. PMID- 22071549 TI - Zinc and human health: an update. AB - The importance of micronutrients in health and nutrition is undisputable, and among them, zinc is an essential element whose significance to health is increasingly appreciated and whose deficiency may play an important role in the appearance of diseases. Zinc is one of the most important trace elements in the organism, with three major biological roles, as catalyst, structural, and regulatory ion. Zinc-binding motifs are found in many proteins encoded by the human genome physiologically, and free zinc is mainly regulated at the single cell level. Zinc has critical effect in homeostasis, in immune function, in oxidative stress, in apoptosis, and in aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson's disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles. It is therefore important that status of zinc is assessed in any case and zinc deficiency is corrected, since the unique properties of zinc may have significant therapeutic benefits in these diseases. In the present paper, we review the zinc as a multipurpose trace element, its biological role in homeostasis, proliferation and apoptosis and its role in immunity and in chronic diseases, such as cancer, diabetes, depression, Wilson's disease, Alzheimer's disease, and other age-related diseases. PMID- 22071551 TI - Genetic linkage analysis of a large family with photoparoxysmal response. AB - In this study, we report the results of a genetic linkage analysis of a large family with photoparoxysmal response, defined by the presence of a photoparoxysmal response (PPR) on EEG. The participants were genotyped using an 8 cM whole genome wide scan, and both parametric and non-parametric linkage analysis were carried out. The parametric analysis by MLINK did not identify any definite conclusion but a region of interest on chromosome 1 near marker D1S2865; and non-parametric linkage analysis found a locus of interest on chromosome 16, near marker D16S2621. The possible confounding factors for, and pathogenic implication of, and the results are discussed. PMID- 22071552 TI - Localization of ictal onset zones in Lennox-Gastaut syndrome (LGS) based on information theoretical time delay analysis of intracranial electroencephalography (iEEG). AB - Precise localization of ictal onset zones is of great clinical importance for successful surgery in patients with intractable drug-resistant epilepsy. Time delay analysis has been one of the most reliable and most widely used computational electroencephalogram (EEG) analysis methods for localizing ictal onset zones. However, the majority of previous studies have only been applied to the localization of ictal onset zones in focal epilepsy. In the present study, we analyzed intracranial EEG (iEEG) recordings acquired from patients with Lennox Gaustaut syndrome (LGS), which is a type of intractable, pediatric, secondary generalized epilepsies with bilaterally synchronous ictal epileptiform discharges. To estimate the ictal onset zones from ictal iEEG recordings, we estimated time delays among iEEG signals based on the information theoretical approach. The results of the time delay analysis applied to the iEEG data of four successfully treated LGS patients corresponded well with the surgical resection areas identified by experienced epileptologists and multiple neuroimaging modalities, suggesting that the time delay analysis may provide useful information on the precise locations of ictal onset zones prior to epilepsy surgery in LGS patients. PMID- 22071553 TI - Ligand based pharmacophore model development for the identification of novel antiepileptic compound. AB - Epilepsy is a common neurological disorder throughout the world which is characterized by recurrent unprovoked epileptic seizures. A need exists for the development of new antiseizure drugs with improved efficacy and tolerability, as several of the currently available antiepileptic drugs (AEDs) have been associated with severe side effects. A ligand based pharmacophore approach has been generated for 44 new antiepileptic compounds with emphasis on the development of new drugs by using LigandScout software and distance estimation using Jmol. The pharmacophore of the compounds contained three features hydrophobic unit, hydrogen bonding domain and electron donor. The pharmacophore models derived were then filtered using the Lipinski's rule of five criteria and orally bio-available compounds were obtained. Thus, this approach was able to reclaim few leads which had projected inhibitory activity alike to most active compounds with suitable calculated drug-like properties and therefore they could be recommended for further studies. PMID- 22071554 TI - Effect of low-frequency electrical stimulation parameters on its anticonvulsant action during rapid perforant path kindling in rat. AB - Low frequency stimulation (LFS) may be considered as a new potential therapy for drug-resistant epilepsy. However, the relation between LFS parameters and its anticonvulsant effects is not completely determined. In this study, the effect of some LFS parameters on its anticonvulsant action was investigated in rats. In all animals, stimulating and recording electrodes were implanted into the perforant path and dentate gyrus, respectively. In one group of animals, kindling stimulations were applied until rats achieved a fully kindled state. In other groups, different patterns of LFS were applied at the end of kindling stimulations during twenty consecutive days. In the first experiment the effect of LFS pulse numbers was investigated on its anticonvulsant action. Animals were divided randomly into three groups and 1, 4, and 8 packages of LFS (each pack contains 200 pulses, 0.1 ms pulse duration at 1 Hz) were applied five minutes after termination of kindling stimulations. Obtained results showed that 4 packages of LFS had the strongest anticonvulsant effects. Therefore, this pattern (4 packages) was used in the next experiment. In the second experiment, 4 packages of LFS were applied at intervals of 30 s and 30 min after termination of kindling stimulations. The strongest anticonvulsant effect was observed in the group received LFS at the interval of 30 s. Therefore, this pattern was selected for the third experiment. In the third experiment the effect of LFS at frequencies of 0.25 Hz and 5 Hz was investigated. The group of animals which received LFS at the frequency of 0.25 Hz showed somehow stronger anticonvulsant effect. The results indicate that different parameters of LFS have important role in induction of LFS anticonvulsant effects. Regarding this view, it seems that the slower LFS frequency and the shorter interval between LFS and kindling stimulations, the stronger anticonvulsant effect will be observed. But there is no direct relation between number of pulses and the magnitude of anticonvulsant effect of LFS. PMID- 22071555 TI - Early clinical features in Dravet syndrome patients with and without SCN1A mutations. AB - BACKGROUND: SCN1A is the most clinically relevant epilepsy gene, most mutations causing Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI). We evaluated clinical differences, if any, between young patients with and without a SCN1A mutations and a definite clinical diagnosis of Dravet syndrome. METHODS: Twenty-five patients with a diagnosis of Dravet Syndrome (7 males, 18 females; mean age at inclusion: 10.3; median: 9+/-7; range: 18 months-30 years) were retrospectively studied. A clinical and genetic study focusing on SCN1A was performed, using DHPLC, gene sequencing and MLPA to detect genomic deletions/duplications. A formal cognitive and behavioral assessment was available for all patients. RESULTS: Analysis revealed SCN1A mutations comprising missense, truncating mutations and genomic deletions/duplications in eighteen patients and no mutation in seven. The phenotype of mutation positive patients was characterized by a higher number of seizures/month in the first year of life, an earlier seizure onset and a higher frequency of episodes of status epilepticus. The cognitive and behavioral profile was slightly worst in mutation positive patients. CONCLUSIONS: These findings confirm that SCN1A gene mutations are strongly associated to a more severe phenotype in patients with Dravet syndrome. PMID- 22071556 TI - Transformation of Solanum tuberosum plastids allows high expression levels of beta-glucuronidase both in leaves and microtubers developed in vitro. AB - Plastid genome transformation offers an attractive methodology for transgene expression in plants, but for potato, only expression of gfp transgene (besides the selective gene aadA) has been published. We report here successful expression of beta-glucuronidase in transplastomic Solanum tuberosum (var. Desiree) plants, with accumulation levels for the recombinant protein of up to 41% of total soluble protein in mature leaves. To our knowledge, this is the highest expression level reported for a heterologous protein in S. tuberosum. Accumulation of the recombinant protein in soil-grown minitubers was very low, as described in previous reports. Interestingly, microtubers developed in vitro showed higher accumulation of beta-glucuronidase. As light exposure during their development could be the trigger for this high accumulation, we analyzed the effect of light on beta-glucuronidase accumulation in transplastomic tubers. Exposure to light for 8 days increased beta-glucuronidase accumulation in soil grown tubers, acting as a light-inducible expression system for recombinant protein accumulation in tuber plastids. In this paper we show that plastid transformation in potato allows the highest recombinant protein accumulation in foliar tissue described so far for this food crop. We also demonstrate that in tubers high accumulation is possible and depends on light exposure. Because tubers have many advantages as protein storage organs, these results could lead to new recombinant protein production schemes based on potato. PMID- 22071557 TI - Pattern electroretinogram progression in glaucoma suspects. AB - PURPOSE: To prospectively monitor progressive changes of retinal ganglion cell function in early glaucoma using the pattern electroretinogram (PERG). METHODS: Fifty-nine patients enrolled as glaucoma suspects were observed untreated over an average of 5.7+/-1.4 years, during which they were tested with PERG (PERGLA paradigm) and standard automated perimetry (SAP) 2 times per year. PERG amplitude and phase were normalized for physiological age-related changes, and linear regressions fitted to the data to calculate progression slopes (signal), slope SE (noise), and corresponding signal-to-noise ratios (SNR=slope/SE). Linear regressions were also used to fit SAP global indices mean deviation (MD) and pattern standard deviation (PSD). RESULTS: On average, progression slopes of PERG amplitude/phase were skewed toward negative values, their mean being significantly (P<0.01) different from zero. In contrast, mean slopes of SAP-MD and PSD were not significantly different from zero. SNRs were higher for PERG than SAP (P<0.01). A substantial number of eyes displayed significant (P<0.05) progression of PERG amplitude (15% to 20%) or PERG phase (16% to 25%). Fewer eyes displayed significant progression of SAP-MD (0% to 2%) or SAP-PSD (4% to 8%). CONCLUSIONS: The PERG displayed clear longitudinal loss of signal (diminished amplitude, phase delay, or both) in a substantial number of eyes of patients, indicating progressive deterioration of retinal ganglion cell function. Progression of SAP global indices MD and PSD was found in a relatively smaller number of eyes. It remains to be established whether PERG progression has predictive value for developing visual dysfunction. PMID- 22071558 TI - Occurrence of infection by Platynosomum illiciens (Braun, 1901) in captive neotropical primates. AB - Platynosomum illiciens (Trematoda, Plagiorchida) is a trematode parasite reported in felids and falconiforms. It was identified in the gall bladder of eight captive neotropical necropsied primates from the National Primate Center (CENP), Ananindeua, State of Para, Brazil. This is the first description of Platynosomum illiciens as a parasite of primates. PMID- 22071562 TI - Deep tissue bio-imaging using two-photon excited CdTe fluorescent quantum dots working within the biological window. AB - A new approach to deep tissue imaging is presented based on 8 nm CdTe semiconductor quantum dots (QDs). The characteristic 800 nm emission was found to be efficiently excited via two-photon absorption of 900 nm photons. The fact that both excitation and emission wavelengths lie within the "biological window" allows for high resolution fluorescence imaging at depths close to 2 mm. These penetration depths have been used to obtain the first deep tissue multiphoton excited fluorescence image based on CdTe-QDs. Due to the large thermal sensitivity of CdTe-QDs, one may envisage, in the near future, their use in high resolution deep-tissue thermal imaging. PMID- 22071563 TI - Functional expression of ionotropic glutamate receptors in the rabbit retinal ganglion cells. AB - It has been known that retinal ganglion cells (RGCs) with distinct morphologies have different physiological properties. It was hypothesized that different functions of RGCs may in part result from various expressions of N-methyl-d aspartate (NMDA), alpha-amino-3-hydroxyl-5-methyl-isoxazole-4-propinoic acid (AMPA), and kainic acid (KA) receptors on their dendrites. In the present study, we aimed to characterize the functional expression of AMPA and NMDA receptors of morphologically identified RGCs in the wholemount rabbit retina. The agmatine (AGB) activation assay was used to reveal functional expression of ionotropic glutamate receptors after the RGCs were targeted by injecting Neurobiotin. To examine the excitability of these glutamate receptors in an agonist specific manner, the lower concentrations of AMPA (2 MUM) and NMDA (100 MUM) were chosen to examine G7 (ON-OFF direction selective ganglion cells) and G11 (alpha ganglion cells) types of RGCs. We found that less than 40% of G7 type RGCs had salient AGB activation when incubated with 2 MUM AMPA or 100 MUM NMDA. The G11 type RGCs also showed similar activation frequencies, except that all of the OFF subtype examined had no AGB permeation under the same AMPA concentration. These results suggest that RGCs with large somata (G7 and G11 types) may express various heterogeneous functional ionotropic glutamate receptors, thus in part rendering their functional diversity. PMID- 22071564 TI - Integration and transmission of distributed deterministic neural activity in feed forward networks. AB - A ten layer feed-forward network characterized by diverging/converging patterns of projection between successive layers of regular spiking (RS) neurons is activated by an external spatiotemporal input pattern fed to Layer 1 in presence of stochastic background activities fed to all layers. We used three dynamical systems to derive the external input spike trains including the temporal information, and three types of neuron models for the network, i.e. either a network formed either by neurons modeled by exponential integrate-and-fire dynamics (RS-EIF, Fourcaud-Trocme et al., 2003), or by simple spiking neurons (RS IZH, Izhikevich, 2004) or by multiple-timescale adaptive threshold neurons (RS MAT, Kobayashi et al., 2009), given five intensities for the background activity. The assessment of the temporal structure embedded in the output spike trains was carried out by detecting the preferred firing sequences for the reconstruction of de-noised spike trains (Asai and Villa, 2008). We confirmed that the RS-MAT model is likely to be more efficient in integrating and transmitting the temporal structure embedded in the external input. We observed that this structure could be propagated not only up to the 10th layer but in some cases it was retained better beyond the 4th downstream layers. This study suggests that diverging/converging network structures, by the propagation of synfire activity, could play a key role in the transmission of complex temporal patterns of discharges associated to deterministic nonlinear activity. This article is part of a Special Issue entitled Neural Coding. PMID- 22071565 TI - Undirected thought: neural determinants and correlates. AB - While goal-directed thinking has received the lion's share of neuroscientific attention, its counterpart--the undirected thought flow that comes to mind unbidden and without effort--has remained largely on the sidelines of scientific research. Such undirected thought, however, forms a large part of our mental experience. The last decade of neuroscientific investigations marked a resurgence of interest and work into the neural basis of undirected thought. This article reviews the current status of the field and examines the research on the three most frequently discussed categories of undirected thought: spontaneous thought, stimulus-independent thought, and mind wandering. The terminology and paradigms for investigating undirected thought are still being developed, while research is gradually moving beyond strictly task- and rest-based paradigms and towards incorporating introspective first-person reports in order to better understand this phenomenon. It is impossible to say at this point that undirected thinking is preferentially linked to any one particular brain system. Although its connection to the default network has been disproportionately emphasized in the literature, other brain networks such as the executive system and the temporal lobe memory network appear to be equally involved. In addition to reviewing the literature, this article also presents novel findings regarding the functional connectivity between large-scale brain networks during mind wandering. These findings reveal the presence of positive functional connectivity between regions of the default and executive networks and negative functional connectivity between the default network and primary sensory cortices. Thus, the default and executive networks can closely cooperate in supporting undirected thought processes, and seem to do so at times when the primary sensory cortices are not busy with the processing of perceptual information from the external environment. This article is part of a Special Issue entitled The Cognitive Neuroscience of Thought. PMID- 22071566 TI - Clinical use of the STOP-BANG questionnaire in patients undergoing sedation for endoscopic procedures. PMID- 22071567 TI - Trends in life jacket wear among recreational boaters: a dozen years (1999-2010) of US observational data. AB - We report results from 12 years of US observational data on life jacket use among recreational boaters based on more than 480,000 boaters in 175,000 boats between 1999 and 2010. The overall wear rate was 21.7 per cent, with sharp differences by age and boat types. We found strong increasing trends in wear rates among youth boaters, but among adults, the only increase was on sailboats. The increasing trend among youth is probably due to a combination of expanding laws for mandatory life jacket use among this age group, and targeted educational campaigns promoting life jacket use for children. Future efforts to increase the prevalence of life jacket wear should target groups with low wear rates and boaters on boats most likely to capsize. Policymakers should give serious consideration to regulations requiring adult boaters to wear life jackets while boating. PMID- 22071568 TI - Laboratory equipment maintenance: a critical bottleneck for strengthening health systems in sub-Saharan Africa? AB - Properly functioning laboratory equipment is a critical component for strengthening health systems in developing countries. The laboratory can be an entry point to improve population health and care of individuals for targeted diseases - prevention, care, and treatment of TB, HIV/AIDS, and malaria, plus maternal and neonatal health - as well as those lacking specific attention and funding. We review the benefits and persistent challenges associated with sustaining laboratory equipment maintenance. We propose equipment management policies as well as a comprehensive equipment maintenance strategy that would involve equipment manufacturers and strengthen local capacity through pre-service training of biomedical engineers. Strong country leadership and commitment are needed to assure development and sustained implementation of policies and strategies for standardization of equipment, and regulation of its procurement, donation, disposal, and replacement. PMID- 22071569 TI - Dietary L-tryptophan alters aggression in juvenile matrinxa Brycon amazonicus. AB - This study evaluated the effect of dietary supplementation with L: -tryptophan (L TRP), a serotonin precursor, on the aggressiveness of juvenile matrinxa Brycon amazonicus. Fish were kept in individual aquaria for 7 days receiving the diets: D1 (control: 0.47% of TRP), D2 (0.94% of TRP), D3 (1.88% of TRP), and D4 (3.76% of TRP). After this, they were grouped with an intruder fish to establish a resident-intruder relationship during periods of 20 min. Blood cortisol, glucose, chloride, sodium and calcium; hemoglobin, hematocrit, red blood cell count and volume; liver glycogen and lipids were measured. Territoriality had significant effect on the aggressiveness of matrinxa (the residents were more aggressive than intruders, P < 0.001) and tryptophan significantly affected their behavior. Fish fed with the D2 diet presented a longer latency until the first attack (P = 0.0069) and bit the intruder fewer times (P = 0.0136) during the period of observation, compared to the control group. The frequency of bites and chases after the first attack was not affected by the dietary supplementation of TRP. Physiological variables were not significantly affected by the diet, except for a moderate increase in cortisol level in fish fed with D2 diet after the fight, indicating slight activation of the hypothalamus-pituitary-interrenal axis. The results show that juvenile matrinxa have aggressive and territorial behavior and that a diet containing 9.4 g TRP kg(-1) alter their aggressiveness, without affecting the stress-related physiological parameters. PMID- 22071571 TI - Optical absorption and excitonic coupling in azobenzenes forming self-assembled monolayers: a study based on density functional theory. AB - Based on the analysis of optical absorption spectra, it has recently been speculated that the excitonic coupling between individual azobenzene functionalized alkanethiols arranged in a self-assembled monolayer (SAM) on a gold surface could be strong enough to hinder collective trans-cis isomerization on top of steric hindrance [Gahl et al., J. Am. Chem. Soc., 2010, 132, 1831]. Using models of SAMs of increasing complexity (dimer, linear N-mers, and two dimensionally arranged N-mers) and density functional theory on the (TD-) B3LYP/6 31G* level, we determine optical absorption spectra, the nature and magnitude of excitonic couplings, and the corresponding spectral shifts. It is found that at inter-monomer distances of about 20 A and above, TD-B3LYP excitation frequencies (and signal intensities) can be well described by the frequently used point dipole approximation. Further, calculated blue shifts in optical absorption spectra account for the experimental observations made for azobenzene/gold SAMs, and hint to the fact that they can indeed be responsible for reduced switching probability in densely packed self-assembled structures. PMID- 22071570 TI - Clinical significance of metabolic tumor volume by PET/CT in stages II and III of diffuse large B cell lymphoma without extranodal site involvement. AB - The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm(3) was the cutoff value. The low MTV group (<220 cm(3)) had longer progression-free survival (PFS) and overall survival (OS), compared with the high MTV group (>=220 cm(3)) (p < 0.001, p < 0.001). Stage II patients had longer survival than those in stage III (PFS, p = 0.011; OS, p = 0.001). The high MTV group had lower PFS and OS patterns, regardless of stage, compared with the low MTV group (p < 0.001, p < 0.001). Multivariate analysis revealed an association of the high MTV group with lower PFS and OS (PFS, hazard ratio (HR) = 5.300, p < 0.001; OS, HR = 7.009, p < 0.001), but not stage III (PFS, p = 0.187; OS, p = 0.054). Assessment of MTV by PET had more potential predictive power than Ann Arbor stage in the patients that received R-CHOP. PMID- 22071572 TI - Gas nanosensor design packages based on tungsten oxide: mesocages, hollow spheres, and nanowires. AB - Achieving proper designs of nanosensors for highly sensitive and selective detection of toxic environmental gases is one of the crucial issues in the field of gas sensor technology, because such designs can lead to the enhancement of gas sensor performance and expansion of their applications. Different geometrical designs of porous tungsten oxide nanostructures, including the mesocages, hollow spheres and nanowires, are synthesized for toxic gas sensor applications. Nanosensor designs with small crystalline size, large specific surface area, and superior physical characteristics enable the highly sensitive and selective detection of low concentration (ppm levels), highly toxic NO(2) among CO, as well as volatile organic compound gases, such as acetone, benzene, and ethanol. The experimental results showed that the sensor response was not only dependent on the specific surface area, but also on the geometries and crystal size of materials. Among the designed nanosensors, the nanowires showed the highest sensitivity, followed by the mesocages and hollow spheres-despite the fact that mesocages had the largest specific surface area of 80.9 m(2) g( - 1), followed by nanowires (69.4 m(2) g( - 1)), and hollow spheres (6.5 m(2) g( - 1)). The nanowire sensors had a moderate specific surface area (69.4 m(2) g( - 1)) but they exhibited the highest sensitivity because of their small diameter (~5 nm), which approximates the Debye length of WO(3). This led to the depletion of the entire volume of the nanowires upon exposure to NO(2), resulting in an enormous increase in sensor resistance. PMID- 22071573 TI - Palliative care for the terminally ill in America: the consideration of QALYs, costs, and ethical issues. AB - The drive for cost-effective use of medical interventions has advantages, but can also be challenging in the context of end-of-life palliative treatments. A quality-adjusted life-year (QALY) provides a common currency to assess the extent of the benefits gained from a variety of interventions in terms of health-related quality of life and survival for the patient. However, since it is in the nature of end-of-life palliative care that the benefits it brings to its patients are of short duration, it fares poorly under a policy of QALY-maximization. Nevertheless, we argue that the goals of palliative care and QALY are not incompatible, and optimal integration of palliative care into the calculation of QALY may reveal a mechanism to modify considerations of how optimal quality of life can be achieved, even in the face of terminal illness. The use of QALYs in resource allocation means that palliative care will always compete with alternative uses of the same money. More research should be conducted to evaluate choices between palliative care and more aggressive therapies for the terminally ill. However, current limited data show that investing in palliative care makes more sense not only ethically, but also financially. PMID- 22071575 TI - The end of health. PMID- 22071574 TI - High-dose rapamycin induces apoptosis in human cancer cells by dissociating mTOR complex 1 and suppressing phosphorylation of 4E-BP1. AB - mTOR, the mammalian target of rapamycin, has been widely implicated in signals that promote cell cycle progression and survival in cancer cells. Rapamycin, which inhibits mTOR with high specificity, has consequently attracted much attention as an anti-cancer therapeutic. Rapamycin suppresses phosphorylation of S6 kinase at nano-molar concentrations, however at higher micro-molar doses, rapamycin induces apoptosis in several human cancer cell lines. While much is known about the effect of low dose rapamycin treatment, the mechanistic basis for the apoptotic effects of high-dose rapamycin treatment is not understood. We report here that the apoptotic effects of high-dose rapamycin treatment correlate with suppressing phosphorylation of the mTOR complex 1 substrate, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4E-BP1). Consistent with this observation, ablation of eIF4E also resulted in apoptorsis in MDA-MB 231 breast cancer cells. We also provide evidence that the differential dose effects of rapamycin are correlated with partial and complete dissociation of Raptor from mTORC1 at low and high doses, respectively. In contrast with MDA-MB-231 cells, MCF-7 breast cancer cells survived rapamycin-induced suppression of 4E-BP1 phosphorylation. We show that survival correlated with a hyper-phosphorylation of Akt at S473 at high rapamycin doses, the suppression of which conferred rapamycin sensitivity. This study reveals that the apoptotic effect of rapamycin requires doses that completely dissociate Raptor from mTORC1 and suppress that phosphorylation of 4E-BP1 and inhibit eIF4E. PMID- 22071576 TI - Commercially available antibodies against human and murine histamine H4-receptor lack specificity. AB - Antibodies are important tools to detect expression and localization of proteins within the living cell. However, for a series of commercially available antibodies which are supposed to recognize G-protein-coupled receptors (GPCR), lack of specificity has been described. In recent publications, antisera against the histamine H4-receptor (H4R), which is a member of the GPCR family, have been used to demonstrate receptor expression. However, a comprehensive characterization of these antisera has not been performed yet. Therefore, the purpose of our study was to evaluate the specificity of three commercially available H4R antibodies. Sf9 insect cells and HEK293 cells expressing recombinant murine and human H4R, spleen cells obtained from H4-/- and from wild type mice, and human CD20+ and CD20- peripheral blood cells were analyzed by flow cytometry and Western blot using three commercially available H4R antibodies. Our results show that all tested H4R antibodies bind to virtually all cells, independently of the expression of H4R, thus in an unspecific fashion. Also in Western blot, the H4R antibodies do not bind to the specified protein. Our data underscore the importance of stringent evaluation of antibodies using valid controls, such as cells of H4R-/- mice, to show true receptor expression and antigen specificity. Improved validation of commercially available antibodies prior to release to the market would avoid time-consuming and expensive validation assays by the user. PMID- 22071578 TI - A comparison of InVivoStat with other statistical software packages for analysis of data generated from animal experiments. AB - InVivoStat is a free-to-use statistical software package for analysis of data generated from animal experiments. The package is designed specifically for researchers in the behavioural sciences, where exploiting the experimental design is crucial for reliable statistical analyses. This paper compares the analysis of three experiments conducted using InVivoStat with other widely used statistical packages: SPSS (V19), PRISM (V5), UniStat (V5.6) and Statistica (V9). We show that InVivoStat provides results that are similar to those from the other packages and, in some cases, are more advanced. This investigation provides evidence of further validation of InVivoStat and should strengthen users' confidence in this new software package. PMID- 22071577 TI - Enalapril reduces germ cell toxicity in streptozotocin-induced diabetic rat: investigation on possible mechanisms. AB - Diabetes mellitus, a state of persistent hyperglycemia, is a major cause of micro and macrovascular diseases. It affects nearly every system in the body including the reproductive system. Abnormalities in spermatogenesis and sexual function have been documented in animal models for both types of diabetes. The purpose of the present study is to determine the possible protective effects of enalapril against the germ cell toxicity in diabetic rat. Sprague-Dawley rats were divided into four groups: (1) control, (2) control + enalapril, (3) diabetic, and (4) diabetic + enalapril. Enalapril was administered per orally for 4 and 8 weeks continuously. After the treatment, animals were sacrificed and blood glucose level, sperm count, sperm DNA damage, apoptotic cell death, immunohistochemistry of 8-oxo- 7,8-dihydro- 2'-deoxyguanosine, and the cellular toxicity were performed. Furthermore, western blotting was performed to evaluate the expression of NFkappaB and COX-2 in testes. The results of the present study indicate that intervention of enalapril ameliorates the sperm DNA damage, reduces the oxidative stress, and down-regulates the expression of NFkappaB and COX-2 expression in streptozotocin-induced diabetic rat. PMID- 22071579 TI - TLE1 is expressed in the majority of primary pleuropulmonary synovial sarcomas. AB - Pleuropulmonary synovial sarcoma (PPSS) is a rare entity, similar to synovial sarcoma of soft tissue (STSS). There are 120 published cases of PPSS, but no studies have explored the expression of TLE1. In soft tissues, it has been proven a useful marker, but in tumors of other sites, its expression has not been explored. The main objective was to study the expression and diagnostic sensitivity and specificity of TLE1 in a group of PPSS, of which the diagnosis was corroborated by fluorescence in situ hybridization confirming t(X;18) in a tissue microarray. Immunohistochemistry including TLE1, vimentin, CD99, CD56, bcl 2, AE1-AE3, EMA, CD34, CK7, CK19, calponin, and S-100 was performed on all PPSS and on 25 control cases (five carcinomas, ten mesotheliomas, and ten thoracic sarcomas). TLE1 was positive in 11 cases (73.3%); bcl-2 and vimentin in 100%; calponin and CD56 in 26.6%; CD99, CK AE1-AE3, CK19, CK7, and EMA in 80%; and S100 negative in all. The only biphasic PPSS was positive for epithelial markers only in the epithelial component. TLE1 was negative in all control cases. TLE1 is expressed in 73% of PPSS, a value inferior to that reported in STSS, but is highly specific for PPSS. TLE1 may therefore be of value in the differential diagnosis of PPSS, but should be used in a panel of antibodies. PMID- 22071580 TI - Blood longitudinal (T1) and transverse (T2) relaxation time constants at 11.7 Tesla. AB - OBJECT: The goal of the study was to determine blood T(1) and T(2) values as functions of oxygen saturation (Y), temperature (Temp) and hematocrit (Hct) at an ultrahigh MR field (11.7 T) and explore their impacts on physiological measurements, including cerebral blood flow (CBF), blood volume (CBV) and oxygenation determination. MATERIALS AND METHODS: T(1) and T(2) were simultaneously measured. Temperature was adjusted from 25 to 40 degrees C to determine Temp dependence; Hct of 0.17-0.51 to evaluate Hct dependence at 25 and 37 degrees C; and Y of 40-100% to evaluate Y dependence at 25 and 37 degrees C. Comparisons were made with published data obtained at different magnetic field strengths (B(0)). RESULTS: T(1) was positively correlated with Temp, independent of Y, and negatively correlated with Hct. T(2) was negatively correlated with Temp and Hct, but positively correlated with Y, in a non-linear fashion. T(1) increased linearly with B(0), whereas T(2) decreased exponentially with B(0). CONCLUSION: This study reported blood T(1) and T(2) measurements at 11.7 T for the first time. These blood relaxation data could have implications in numerous functional and physiological MRI studies at 11.7 T. PMID- 22071581 TI - Orientational dependent sensitivities of T2 and T1rho towards trypsin degradation and Gd-DTPA2- presence in bovine nasal cartilage. AB - OBJECTIVE: To study the orientational dependencies of T(2) and T(1rho) in native and trypsin-degraded bovine nasal cartilage, with and without the presence of 1 mM Gd-DTPA(2-). MATERIALS AND METHODS: Sixteen specimens were prepared in two orthogonal fibril directions (parallel and perpendicular), treated using different protocols (native, Gd treated, trypsin-treated, and combination), and imaged using MUMRI at 0 degrees and 55 degrees (the magic angle) fibril orientations with respect to the magnetic field B(0). Two-dimensional (2D) T(2) and T(1rho) images were then calculated quantitatively. RESULTS: Without Gd, native perpendicular tissues demonstrated significant T(1rho) dispersion (including T(2) at the zero spin-lock field) at 0 degrees and less dispersion at 55 degrees , while native parallel specimens exhibited smaller T(1rho) dispersion at both 0 degrees and 55 degrees . Trypsin degradation caused a minimum 50% increase in T(1rho). With Gd, trypsin degradation caused significant reduction in T(1rho) values up to 60%. CONCLUSION: The collagen orientation in nasal cartilage can influence T(2) and T(1rho) MRI of cartilage. Without Gd, T(1rho) was sensitive to the proteoglycan content and its sensitivity was nearly constant regardless of fibril orientation. In comparison, the T(2) sensitivity to proteoglycan was dependant upon fibril orientation, i.e., more sensitive at 55 degrees than 0 degrees . When Gd ions were present, both T(2) and T(1rho) became insensitive to the proteoglycan content. PMID- 22071582 TI - A correction method for streak artifacts in gradient-echo EPI using spin-echo EPI reference data. AB - OBJECTIVE: To analyze the streak artifacts in a gradient-echo echo planar imaging (GE-EPI) sequence and to propose a correction method for the Nyquist ghost artifacts that does not cause streak artifacts in the GE-EPI imaging. MATERIALS AND METHODS: Several GE-EPI imaging experiments with various reference scans, using both GE-EPI and SE-EPI scan data, were performed to analyze the streak artifacts and to investigate the spin dephasing phenomena of the GE-EPI reference scan. In addition, the analysis based on the spin dephasing was undertaken in order to demonstrate that the SE-EPI reference data can be used for the correction of the GE-EPI main scan data. RESULTS: The experimental results confirmed that the improvement of the reference data using either signal averaging or a large flip angle cannot guarantee perfect correction of the streak artifact if the noise is not completely removed. Due to the main field inhomogeneity, the spins of the GE-EPI reference data were dephased in multiple echo signals. The proposed correction method, which uses a SE-EPI reference scan for the GE-EPI images, eliminates the N/2 ghost artifacts without producing streak artifacts. CONCLUSION: It is believed that the proposed phase error correction scheme can improve the EPI performance in high field MRIs with higher magnetic field inhomogeneities. PMID- 22071583 TI - Recent changes to UK newborn resuscitation guidelines. PMID- 22071584 TI - Depression and cognitive deficits in geriatric schizophrenia. AB - OBJECTIVE: Past reports have found patients with comorbid depression and schizophrenia spectrum disorders exhibit greater deficits in memory and attention compared to schizophrenia spectrum disorder patients without depressive symptoms. However, in contrast to younger schizophrenia patients, the few past studies using cognitive screens to examine the relationship between depression and cognition in inpatient geriatric schizophrenia have found that depressive symptomatology was associated with relatively enhanced cognitive performance. In the current study we examined the relationship between depressive symptoms and cognitive deficits in geriatric schizophrenia spectrum disorder patients (n=71; mean age=63.7) on an acute psychiatric inpatient service. METHOD: Patients completed a battery of cognitive tests assessing memory, attention and global cognition. Symptom severity was assessed via the PANSS and Calgary Depression Scale for Schizophrenia. RESULTS: Results revealed that geriatric patients' depression severity predicted enhancement of their attentional and verbal memory performance. Patients' global cognitive functioning and adaptive functioning were not associated with their depression severity. CONCLUSION: Contrary to patterns typically seen in younger patients and non-patient groups, increasing depression severity is associated with enhancement of memory and attention in geriatric schizophrenia spectrum disorder patients. Also, diverging from younger samples, depression severity was unassociated with patients adaptive and global cognitive functioning. PMID- 22071585 TI - Social mixing patterns within a South African township community: implications for respiratory disease transmission and control. AB - A prospective survey of social mixing patterns relevant to respiratory disease transmission by large droplets (e.g., influenza) or small droplet nuclei (e.g., tuberculosis) was performed in a South African township in 2010. A total of 571 randomly selected participants recorded the numbers, times, and locations of close contacts (physical/nonphysical) and indoor casual contacts met daily. The median number of physical contacts was 12 (interquartile range (IQR), 7-18), the median number of close contacts was 20 (IQR, 13-29), and the total number of indoor contacts was 30 (IQR, 12-54). Physical and close contacts were most frequent and age-associative in youths aged 5-19 years. Numbers of close contacts were 40% higher than in corresponding populations in industrialized countries (P < 0.001). This may put township communities at higher risk for epidemics of acute respiratory illnesses. Simulations of an acute influenza epidemic predominantly involved adolescents and young adults, indicating that control strategies should be directed toward these age groups. Of all contacts, 86.2% occurred indoors with potential exposure to respiratory droplet nuclei, of which 27.2%, 20.1%, 20.0%, and 8.0% were in transport, own household, creche/school, and work locations, respectively. Indoor contact time was long in households and short during transport. High numbers of indoor contacts and intergenerational mixing in households and transport may contribute to exceptionally high rates of tuberculosis transmission reported in the community. PMID- 22071586 TI - Birth size and childhood growth as determinants of physical functioning in older age: the Helsinki Birth Cohort Study. AB - The study reports on the associations of infant and childhood anthropometric measurements, early growth, and the combined effect of birth weight and childhood body mass index with older age physical functioning among 1,999 individuals born in 1934-1944 and belonging to the Helsinki Birth Cohort Study. Physical functioning was assessed by the Short Form 36 scale. Anthropometric data from infancy and childhood were retrieved from medical records. The risk of lower Short Form 36 physical functioning at the mean age of 61.6 years was increased for those with birth weight less than 2.5 kg compared with those weighing 3.0-3.5 kg at birth (odds ratio (OR) = 2.73, 95% confidence interval (CI): 1.57, 4.72). The gain in weight from birth to age 2 years was associated with decreased risk of lower physical functioning for a 1-standard deviation increase (OR = 0.84, 95% CI: 0.75, 0.94). The risk of lower physical functioning was highest for individuals with birth weight in the lowest third and body mass index at 11 years of age in the highest third compared with those whose birth weight was in the middle third and body mass index at age 11 years was in the highest third (OR = 3.08, 95% CI: 1.83, 5.19). The increasing prevalence of obesity at all ages and the aging of populations warrant closer investigation of the role of weight trajectories in old age functional decline. PMID- 22071587 TI - Childhood and adult socioeconomic position, cumulative lead levels, and pessimism in later life: the VA Normative Aging Study. AB - Pessimism, a general tendency toward negative expectancies, is a risk factor for depression and also heart disease, stroke, and reduced cancer survival. There is evidence that individuals with higher lead exposure have poorer health. However, low socioeconomic status (SES) is linked with higher lead levels and greater pessimism, and it is unclear whether lead influences psychological functioning independently of other social factors. The authors considered interrelations among childhood and adult SES, lead levels, and psychological functioning in data collected on 412 Boston area men between 1991 and 2002 in a subgroup of the VA Normative Aging Study. Pessimism was measured by using the Life Orientation Test. Cumulative (tibia) lead was measured by x-ray fluorescence. Structural equation modeling was used to quantify the relations as mediated by childhood and adult SES, controlling for age, health behaviors, and health status. An interquartile range increase in lead quartile was associated with a 0.37 increase in pessimism score (P < 0.05). Low childhood and adult SES were related to higher tibia lead levels, and both were also independently associated with higher pessimism. Lead maintained an independent association with pessimism even after childhood and adult SES were considered. Results demonstrate an interrelated role of lead burden and SES over the life course in relation to psychological functioning in older age. PMID- 22071589 TI - Quitting smoking among adults--United States, 2001-2010. AB - Quitting smoking is beneficial to health at any age, and cigarette smokers who quit before age 35 years have mortality rates similar to those who never smoked. From 1965 to 2010, the prevalence of cigarette smoking among adults in the United States decreased from 42.4% to 19.3%, in part because of an increase in the number who quit smoking. Since 2002, the number of former U.S. smokers has exceeded the number of current smokers. Mass media campaigns, increases in the prices of tobacco products, and smoke-free policies have been shown to increase smoking cessation. In addition, brief cessation advice by health-care providers; individual, group, and telephone counseling; and cessation medications are effective cessation treatments. To determine the prevalence of 1) current interest in quitting smoking, 2) successful recent smoking cessation, 3) recent use of cessation treatments, and 4) trends in quit attempts over a 10-year period, CDC analyzed data from the 2001--2010 National Health Interview Surveys (NHIS). This report summarizes the results of that analysis, which found that, in 2010, 68.8% of adult smokers wanted to stop smoking, 52.4% had made a quit attempt in the past year, 6.2% had recently quit, 48.3% had been advised by a health professional to quit, and 31.7% had used counseling and/or medications when they tried to quit. The prevalence of quit attempts increased during 2001- 2010 among smokers aged 25--64 years, but not among other age groups. Health-care providers should identify smokers and offer them brief cessation advice at each visit; counseling and medication should be offered to patients willing to make a quit attempt. PMID- 22071590 TI - Global routine vaccination coverage, 2010. AB - The Expanded Program on Immunization was established by the World Health Organization (WHO) in 1974 to ensure universal access to routinely recommended childhood vaccines. Six vaccine-preventable diseases initially were targeted: tuberculosis, poliomyelitis, diphtheria, tetanus, pertussis, and measles. In 1974, fewer than 5% of the world's infants were fully immunized; by 2005, global coverage with the third dose of diphtheria-tetanus-pertussis (DTP) vaccine (DTP3) was 79%, but many children, especially those living in poorer countries, still were not being reached. That year, WHO and the United Nations Children's Fund (UNICEF) developed the Global Immunization Vision and Strategy (GIVS), with the aim of decreasing vaccine-preventable disease--related morbidity and mortality by improving national immunization programs. One goal of GIVS was for all countries to achieve 90% national DTP3 coverage by 2010. This report summarizes the status of vaccination coverage globally and regionally in 2010 and progress toward meeting the GIVS goal. In 2010, 130 (67%) countries had achieved 90% DTP3 coverage, and an estimated 85% of infants worldwide had received at least 3 doses of DTP vaccine. However, 19.3 million children were not fully vaccinated and remained at risk for diphtheria, tetanus, and pertussis and other vaccine preventable causes of morbidity and mortality; approximately 50% of these children live in India, Nigeria, and the Democratic Republic of Congo. Despite the overall improvement in vaccination coverage during the past 37 years, routine vaccination programs need to be strengthened globally, especially in countries with the greatest numbers of unvaccinated children. PMID- 22071588 TI - The Nox family of NADPH oxidases: friend or foe of the vascular system? AB - NADPH (nicotinamide adenine dinucleotide phosphate) oxidases are important sources of reactive oxygen species (ROS). In the vascular system, ROS can have both beneficial and detrimental effects. Under physiologic conditions, ROS are involved in signaling pathways that regulate vascular tone as well as cellular processes like proliferation, migration and differentiation. However, high doses of ROS, which are produced after induction or activation of NADPH oxidases in response to cardiovascular risk factors and inflammation, contribute to the development of endothelial dysfunction and vascular disease. In vascular cells, the NADPH oxidase isoforms Nox1, Nox2, Nox4, and Nox5 are expressed, which differ in their activity, response to stimuli, and the type of ROS released. This review focuses on the specific role of different NADPH oxidase isoforms in vascular physiology and their potential contributions to vascular diseases. PMID- 22071591 TI - Progress toward poliomyelitis eradication--Afghanistan and Pakistan, January 2010 September 2011. AB - Indigenous transmission of wild poliovirus (WPV) has never been interrupted in Afghanistan, Pakistan, India, and Nigeria. Among those countries, Afghanistan and Pakistan represent a common epidemiologic reservoir. This report updates previous reports (1,4) and describes polio eradication activities and progress in Afghanistan and Pakistan during January 2010--September 2011, as of October 31, 2011, and planned activities during 2011--2012 to address challenges to polio eradication. In Afghanistan, WPV transmission during 2010--2011 predominantly occurred in the conflict-affected South Region and the adjacent Farah Province of the West Region. During 2010, 25 WPV cases were confirmed in Afghanistan, compared with 38 in 2009; 42 WPV cases were confirmed during January--September 2011, compared with 19 for the same period in 2010. In Pakistan, WPV transmission during 2010--2011occurred both in conflict-affected, inaccessible areas along the common border with Afghanistan and in accessible areas; 144 WPV cases were confirmed in 2010, compared with 89 in 2009, and 120 WPV cases were confirmed during January--September 2011, compared with 93 during the same period in 2010. In Pakistan, the president launched a National Emergency Action Plan for polio eradication in January 2011, emphasizing the key role and responsibility of political and health-care leaders at the district and subdistrict (union council) levels. Enhanced commitment, management, and oversight by provincial and district authorities will be needed to achieve further progress toward interruption of WPV transmission in Pakistan. Continued efforts also will be needed to enhance the safety of vaccination teams within insecure areas of both countries. PMID- 22071592 TI - Update on herpes zoster vaccine: licensure for persons aged 50 through 59 years. AB - Herpes zoster vaccine (Zostavax, Merck & Co., Inc.) was licensed and recommended in 2006 for prevention of herpes zoster among adults aged 60 years and older. In March 2011, the Food and Drug Administration (FDA) approved the use of Zostavax in adults aged 50 through 59 years. In June 2011, the Advisory Committee on Immunization Practices (ACIP) declined to recommend the vaccine for adults aged 50 through 59 years and reaffirmed its current recommendation that herpes zoster vaccine be routinely recommended for adults aged 60 years and older. PMID- 22071595 TI - Excited-state dynamics of phenol-pyridinium biaryl. AB - The excited-state dynamics of a donor-acceptor phenol-pyridinium biaryl cation was investigated in various solvents by femtosecond transient absorption spectroscopy and temperature dependent steady-state emission measurements. After excitation to a near-planar Franck-Condon delocalized excited S(1)(DE) state with mesomeric character, three fast relaxation processes are well resolved: solvation, intramolecular rearrangement leading to a twisted charge-shift (CSh) S(1) state with localized character, and excited-state proton transfer (ESPT) to the solvent leading to the phenoxide-pyridinium zwitterion. The proton transfer kinetics depends on the proton accepting character of the solvent whereas the interring torsional kinetics depends on the solvent polarity and viscosity. In nitriles, ESPT does not occur and interring twisting arises with no significant intrinsic barrier, but still slower than solvation. The CSh state is notably fluorescent. In alcohols and water, ESPT is faster than the solvation and DE -> CSh relaxation processes and yields the zwitterion hot ground state, which strongly quenches the fluorescence. In THF, solvation and interring twisting occur first, leading to the fully relaxed, weakly fluorescent CSh state, followed by slow ESPT towards the zwitterion. At low temperature (77 K), the large viscous barrier of the solvent inhibits the torsional relaxation but ESPT still arises to some extent. Strong emission from the DE geometry and planar zwitterion is thus observed. Finally, quantum chemical calculations were performed on the ground and excited state of model phenol-pyridinium and phenoxide-pyridinium compounds. Strong S(1) state energy stabilization is predicted upon twisting in both cases, consistent with a fast relaxation towards the perpendicular geometry. A substantial S(0)-S(1) energy gap is still present for the twisted cationic species, which can explain the long-lived emission of the CSh state in nitriles. A quite different situation arises with the zwitterion for which the S(0)-S(1) energy gap predicted at the twisted geometry is very small. This suggests a close lying conical intersection and can account for the strong fluorescence quenching observed in solvents where the zwitterion is produced by ESPT. PMID- 22071594 TI - Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid. AB - Endemic (Balkan) nephropathy is a chronic tubulointerstitial disease frequently accompanied by urothelial cell carcinomas of the upper urinary tract. This disorder has recently been linked to exposure to aristolochic acid, a powerful nephrotoxin and human carcinogen. Following metabolic activation, aristolochic acid reacts with genomic DNA to form aristolactam-DNA adducts that generate a unique TP53 mutational spectrum in the urothelium. The aristolactam-DNA adducts are concentrated in the renal cortex, thus serving as biomarkers of internal exposure to aristolochic acid. Here, we present molecular epidemiologic evidence relating carcinomas of the upper urinary tract to dietary exposure to aristolochic acid. DNA was extracted from the renal cortex and urothelial tumor tissue of 67 patients that underwent nephroureterectomy for carcinomas of the upper urinary tract and resided in regions of known endemic nephropathy. Ten patients from nonendemic regions with carcinomas of the upper urinary tract served as controls. Aristolactam-DNA adducts were quantified by (32)P postlabeling, the adduct was confirmed by mass spectrometry, and TP53 mutations in tumor tissues were identified by chip sequencing. Adducts were present in 70% of the endemic cohort and in 94% of patients with specific A:T to T:A mutations in TP53. In contrast, neither aristolactam-DNA adducts nor specific mutations were detected in tissues of patients residing in nonendemic regions. Thus, in genetically susceptible individuals, dietary exposure to aristolochic acid is causally related to endemic nephropathy and carcinomas of the upper urinary tract. PMID- 22071596 TI - Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4). AB - PURPOSE: This Phase I study determined the maximum-tolerated dose (MTD) of afatinib (Afatinib is an investigational compound and its safety and efficacy have not yet been established) (BIBW 2992; trade name not yet approved by FDA), an irreversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER)1 and 2, up to a dose of 50 mg/day in advanced non-small cell lung cancer (NSCLC), to establish the recommended dose for Phase II. METHODS: Patients with advanced NSCLC who had received prior platinum-doublet chemotherapy and/or erlotinib/gefitinib therapy, or who were ineligible for, or not amenable to, treatment with established therapies, received oral afatinib once daily. The MTD was determined based on dose-limiting toxicities (DLTs); other assessments included safety, pharmacokinetic profile, antitumour activity according to response evaluation criteria in solid tumours and EGFR/HER1 mutation analysis where possible. RESULTS: Twelve evaluable patients were treated at doses of 20-50 mg/day. One DLT was observed at 50 mg/day in Course 1 (Grade 3 mucositis). The most frequent drug-related adverse events were diarrhoea, dry skin, stomatitis, rash, paronychia and anorexia; most were Grade 1 or 2. Six out of 12 patients had tumour size reductions; durable stable disease was achieved in three patients including one with EGFR/HER1 exon 19 and T790 M mutations. Peak plasma concentrations of afatinib were reached 3-4 h after administration and declined with a half-life of 30-40 h. Afatinib 50 mg/day was well tolerated with an acceptable safety profile during Phase I. CONCLUSION: Recommended dose for Phase II was defined as 50 mg/day for Japanese patients; the same as for non-Japanese patients. PMID- 22071597 TI - Sorafenib for hepatocellular carcinoma according to Child-Pugh class of liver function. PMID- 22071599 TI - SERS assisted ultra-fast peptidic screening: a new tool for drug discovery. AB - Herein we present a direct label-free ultra-fast method for the identification and classification of the active members of a combinatorial library directly on the solid support used for their synthesis. The method is based on the appropriate functionalization of polyethylene glycol grafted polystyrene (TentaGel(r)) microbeads with Au@Ag nanoparticles, the use of these materials directly as solid-phase supports for the synthesis of combinatorial libraries of peptides and the subsequent SERS analysis for identification of each peptide on each bead. PMID- 22071600 TI - Image-quality assessment method for digital phase-contrast imaging based on two dimensional power spectral analysis. AB - With use of the phase shift of X-rays that occurs when they pass through an object, phase-contrast imaging (herein referred to as "phase imaging") can produce images different from those of conventional contact imaging (herein referred to as "conventional imaging"). For this reason, assessment of the image quality based on noise-equivalent quanta (NEQ) and detective quantum efficiency (DQE) which does not include object-based information may not be appropriate for comparison of image quality between phase and conventional images. As an alternative method, we conceived a new image-quality assessment method with images that contain information about an object. First, we constructed images with an object and without an object under the same imaging parameters; then, we obtained two-dimensional power spectra by Fourier transform of those images. Second, we calculated the radial direction distribution function with the power spectra, and the distribution of signal intensity, which we defined as a signal intensity distribution function (SIDF). In this way, differences in image quality were evaluated relatively based on the SIDF of the imaged object. In our study, we first confirmed that phase-imaging evaluation was not appropriate by comparing NEQ and DQE of conventional, magnification, and phase imaging. Further, comparing the image quality of projected plant seeds by employing conventional, magnification, and phase imaging, we found that the phase-imaging method provided a higher image quality regarding edge sharpness than did conventional and magnification imaging. Therefore, based on these results, our image assessment method is considered useful for evaluation of images which include object-based information. PMID- 22071601 TI - Outcomes of infants exposed to multiple antidepressants during pregnancy: results of a cohort study. AB - BACKGROUND: A single study has been published documenting an increased risk for adverse pregnancy outcomes following use of more than one antidepressant during pregnancy. OBJECTIVE: To examine whether multiple antidepressant use is associated with increased rates of major malformations, spontaneous abortions (SA), therapeutic abortions (TA), stillbirths, preterm birth, low birth weight, small for gestational age (SGA) and admission to the neonatal intensive care unit (NICU). METHODS: Information from the Motherisk Program's prospectively collected database of 1243 women with gestational exposure to antidepressants. We compared pregnancy outcomes of 89 women exposed to >1 antidepressants, 89 taking one antidepressant, and 89 women not exposed to antidepressants (n= 267). Women were matched for maternal age, smoking and alcohol use. Groups were compared using odds ratios and ANOVA. RESULTS: 11/89 (12%) took 3 and 78 (88%) took 2 antidepressants. There were no statistically significant differences in any of the outcomes analyzed among the 3 groups except for a lower mean gestational age at birth in the multi-antidepressant group (0.9 week, P=0.036). There were 9 admissions to NICU from the antidepressant groups and 3 from the non-exposed group; but this did not reach statistical significance. CONCLUSIONS: There is a small risk of preterm delivery that is associated with exposure to antidepressant therapy, although the clinical relevance remains to be determined. PMID- 22071602 TI - Creation of stable molecular junctions with a custom-designed scanning tunneling microscope. AB - The scanning tunneling microscope break junction (STMBJ) technique is a powerful approach for creating single-molecule junctions and studying electrical transport in them. However, junctions created using the STMBJ technique are usually mechanically stable for relatively short times (<1 s), impeding detailed studies of their charge transport characteristics. Here, we report a custom-designed scanning tunneling microscope that enables the creation of metal-single molecule metal junctions that are mechanically stable for more than 1 minute at room temperature. This stability is achieved by a design that minimizes thermal drift as well as the effect of environmental perturbations. The utility of this instrument is demonstrated by performing transition voltage spectroscopy-at the single-molecule level-on Au-hexanedithiol-Au, Au-octanedithiol-Au and Au decanedithiol-Au junctions. PMID- 22071604 TI - Experiences as visiting professor at King Saud University, Riyadh, Saudi Arabia. PMID- 22071603 TI - Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation. AB - PURPOSE: MicroRNAs play important roles in cancer development, progression, and metastasis. The aim of this study was to determine whether altered microRNA-155 expression is associated with hepatocellular carcinoma (HCC) recurrence and prognosis following orthotopic liver transplantation (OLT). METHODS: Tissue specimens from 100 HCC patients following OLT were recruited. MicroRNA-155 expression levels were detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of microRNA-155 expression with survival of patients. MicroRNA-155 expression levels of two HCC cell lines (HepG2 and SMMC-7721) and normal liver tissue were quantified using qRT-PCR. The potential function of miR-155 on invasiveness was evaluated in the above HCC cell lines. RESULTS: We found that microRNA-155 expression levels were high in tumor tissues in patients with post-OLT HCC recurrence (n = 45) compared with those in patients with non-recurrence (n = 55) (P = 0.001) and correlated with micro vascular invasion of HCC tissue samples (P = 0.001). Patients with higher miR-155 expression had significantly poorer recurrence-free survival (RFS, log rank P < 0.001) and overall survival (OS, log rank P < 0.001). Multivariate analysis revealed that high miR-155 expression was an independent predictor of poor prognosis (HR 2.748, P = 0.001 for RFS; HR 5.752, P < 0.001 for OS). In addition, the invasiveness of HCC cells was significantly increased by higher microRNA-155 expression. CONCLUSIONS: MicroRNA-155 is a candidate oncogenic microRNA and plays an important role in promoting HCC cells invasion. Our findings suggest that microRNA-155 may serve as a novel biomarker for tumor recurrence and survival of HCC patients following OLT. PMID- 22071605 TI - Comprehensive study of proteins that interact with microcystin-LR. AB - We carried out a comprehensive study of proteins that exhibit specific interactions with a naturally occurring toxin, microcystin (MC)-LR, in order to gain insight into the unknown underlying mechanism of MC virulence. This audacious study employed a simple affinity test that used MC-LR immobilized on an original ethylene oxide based monolithic solid phase (Moli-gel), and swine liver lysate. Some of the proteins that interacted with MC-LR on this original affinity resin were separated by SDS-PAGE, measured by nano-LC/MS/MS after trypsin digestion, and identified using a Mascot database search. Protein sequence analyses revealed that glutathione S-transferase (GST) was one of the candidate target proteins for MC-LR. This protein was confirmed as a target protein for MC LR based on the results of for the inhibition of an enzymatic reaction by Dhb-MC LR. Moreover, L-3-hydroxyacyl coenzyme A dehydrogenase (HDHA) was shown to be one of the proteins that specifically interacts with MC-LR. Our results demonstrated that our analytical systems based on an original affinity resin and nano-LC/MS/MS were effective for target protein research. PMID- 22071606 TI - Raman-spectroscopy-based noninvasive microanalysis of native lignin structure. AB - A new robust, noninvasive, Raman microspectroscopic method is introduced to analyze the structure of native lignin. Lignin spectra of poplar, Arabidopsis, and Miscanthus were recovered and structural differences were unambiguously detected. Compositional analysis of 4-coumarate-CoA ligase suppressed transgenic poplar showed that the syringyl-to-guaiacyl ratio decreased by 35% upon the mutation. A cell-specific compositional analysis of basal stems of Arabidopsis showed similar distributions of S and G monolignols in xylary fiber cells and interfascicular cells. PMID- 22071607 TI - Determination of perfluorinated chemicals in food and drinking water using high flow solid-phase extraction and ultra-high performance liquid chromatography/tandem mass spectrometry. AB - For this study, we developed methods of determining ten perfluorinated chemicals in drinking water, milk, fish, beef, and pig liver using high-flow automated solid-phase extraction (SPE) and ultra-high performance liquid chromatography/tandem mass spectrometry. The analytes were separated on a core shell Kinetex C18 column. The mobile phase was composed of methanol and 10-mM N methylmorpholine. Milk was digested with 0.5 N potassium hydroxide in Milli-Q water, and was extracted with an Atlantic HLB disk to perform automated SPE at a flow rate ranged from 70 to 86 mL/min. Drinking water was directly extracted by the SPE. Solid food samples were digested in alkaline methanol and their supernatants were diluted and also processed by SPE. The disks were washed with 40% methanol/60% water and then eluted with 0.1% ammonium hydroxide in methanol. Suppression of signal intensity of most analytes by matrixes was lower than 50%; it was generally lower in fish and drinking water but higher in liver. Most quantitative biases and relative standard deviations were lower than 15%. The limits of detection for most analytes were sub-nanograms per liter for drinking water and sub-nanograms per gram for solid food samples. This method greatly shortened the time and labor needed for digestion, SPE, and liquid chromatography. This method has been applied to analyze 14 types of food samples. Perfluorooctanoic acid was found to be the highest among the analytes (median at 3.2-64 ng/g wet weight), followed by perfluorodecanoic acid (0.7-25 ng/g) and perfluorododecanoic acid (0.6-15 ng/g). PMID- 22071608 TI - Development of a multiplex DNA-based traceability tool for crop plant materials. AB - The authenticity of food is of increasing importance for producers, retailers and consumers. All groups benefit from the correct labelling of the contents of food products. Producers and retailers want to guarantee the origin of their products and check for adulteration with cheaper or inferior ingredients. Consumers are also more demanding about the origin of their food for various socioeconomic reasons. In contrast to this increasing demand, correct labelling has become much more complex because of global transportation networks of raw materials and processed food products. Within the European integrated research project 'Tracing the origin of food' (TRACE), a DNA-based multiplex detection tool was developed the padlock probe ligation and microarray detection (PPLMD) tool. In this paper, this method is extended to a 15-plex traceability tool with a focus on products of commercial importance such as the emmer wheat Farro della Garfagnana (FdG) and Basmati rice. The specificity of 14 plant-related padlock probes was determined and initially validated in mixtures comprising seven or nine plant species/varieties. One nucleotide difference in target sequence was sufficient for the distinction between the presence or absence of a specific target. At least 5% FdG or Basmati rice was detected in mixtures with cheaper bread wheat or non-fragrant rice, respectively. The results suggested that even lower levels of (un-)intentional adulteration could be detected. PPLMD has been shown to be a useful tool for the detection of fraudulent/intentional admixtures in premium foods and is ready for the monitoring of correct labelling of premium foods worldwide. PMID- 22071609 TI - Last issue for the 25th anniversary year for the Journal of Perinatal and Neonatal Nursing. PMID- 22071610 TI - "Pit to distress": is this an evidence-based strategy? PMID- 22071611 TI - Strategies for increasing parent participation in the neonatal intensive care unit. PMID- 22071612 TI - Social media: friend and foe. PMID- 22071613 TI - Internet resources. PMID- 22071614 TI - Periodontal disease in pregnancy: review of the evidence and prevention strategies. AB - This article reviews the current research on periodontal disease and treatment and its potential impact on maternal and newborn outcomes and provides recommendations for care management and prevention. These guidelines will be helpful for nurse professionals who are in a unique position to counsel pregnant women to improve the oral health of expectant mothers. PMID- 22071615 TI - African American women's infant feeding choices: prenatal breast-feeding self efficacy and narratives from a black feminist perspective. AB - PURPOSE: Examining prenatal breast-feeding self-efficacy and infant feeding decisions among African American women using a mixed-method approach. A black feminist philosophy was used to keep women's experiences as the central research focus. METHOD: The Prenatal Breast-feeding Self-efficacy Scale was used to determine differences between intended breast-feeders and formula users among 59 women. Seventeen narrative interviews were conducted to analyze postpartum accounts of actual feeding practices. RESULTS: Both groups (intended breast- or formula-feeders) demonstrated confidence in their ability to breast-feed. Women planning to breast-feed (M = 82.59, SD = 12.53) scored significantly higher than anticipated formula users (M = 70, SD = 15.45), P = .001 (2-tailed). Four of the six themes emerging from narrative analysis were similar to categories of self efficacy: performance accomplishments, vicarious experiences, verbal persuasions, and physiological reactions. In addition, themes of social embarrassment and feelings of regret were identified. CONCLUSION: Although African American women in this study rated themselves overall as confident with breast-feeding, several narratives about actual feeding choices indicated ambivalence. Women planning to breast-feed need continued support from their healthcare providers throughout the childbearing year. Furthermore, prenatal and immediate postpartum opportunities may exist for nurses to encourage breast-feeding among individuals who initially plan formula use. PMID- 22071617 TI - Developing a bereavement program in the newborn intensive care unit. AB - The mortality rate for newborns in the United States is 4.56 per 1000 live births. Newborn intensive care unit staff is an integral part in helping families deal with bereavement over the loss of their child. This article describes how one newborn intensive care unit worked through the process to develop a comprehensive program to help families in their time of grief. On the basis of personal experiences shared by families and staff, the current practice was updated. Presented also will be 2 case studies and photos of the bereavement materials used. PMID- 22071618 TI - O father, where art thou? Parental NICU visiting patterns during the first 28 days of life of very low-birth-weight infants. AB - To study the frequency and duration of parental visits to neonatal intensive care units (NICU) during the first 28 days of life of preterm infants in relation to medical variables, sociodemographic factors, and subsequent outpatient follow-up examinations. Retrospective chart review of 127 infants with a birth weight less than 1500 g born between Jan 1, 2009, and Dec 31, 2009, at 2 tertiary NICUs. The average frequency of parental visits during the first 28 days of life declined significantly over time (P < .05) while the duration of visits remained constant. Average frequency and duration of visits per day were consistently lower in fathers than in mothers (median [interquartile range]: 0.6 [0.4-1.0] per day vs 1.1 [0.9-1.4] per day, 72.5 [32.1-108.9 [min/d vs 133.4 [75.4-174.3] min/d). While a history of treatment for infertility was correlated with significantly more frequent and longer parental NICU visits in the first 2 weeks, having older children at home was correlated with shorter visits during the first week. Visiting patterns showed no relation to attendance at follow-up examinations at 6 months corrected age. Mothers spend more time with their preterm infants in NICUs than fathers. We suggest measures to increase paternal involvement with hospitalized preterm infants. PMID- 22071619 TI - Supporting oral feeding in fragile infants: an evidence-based method for quality bottle-feedings of preterm, ill, and fragile infants. AB - Successful oral feeding of preterm and other ill and fragile infants is an interactive process that requires (1) sensitive, ongoing assessment of an infant's physiology and behavior, (2) knowledgeable decisions that support immediate and long-term enjoyment of food, and (3) competent skill in feeding. Caregivers can support feeding success by using the infant's biological and behavioral channels of communication to inform their feeding decisions and actions. The Supporting Oral Feeding in Fragile Infants (SOFFI) Method is described here with text, algorithms, and reference guides. Two of the algorithms and the reference guides are published separately as Philbin, Ross. SOFFI Reference Guides: Text, Algorithms, and Appendices (in review). The information in all of these materials is drawn from sound research findings and, rarely, when such findings are not available, from expert, commonly accepted clinical practice. If the quality of a feeding takes priority over the quantity ingested, feeding skill develops pleasurably and at the infant's own pace. Once physiologic organization and behavioral skills are established, an affinity for feeding and the ingestion of sufficient quantity occur naturally, often rapidly, and at approximately the same postmenstrual age as volume-focused feedings. Nurses, therapists, and parents alike can use the SOFFI Method to increase the likelihood of feeding success in the population of infants at risk for feeding problems that emerge in infancy and extend into the preschool years. PMID- 22071622 TI - After 25 years of JPNN: are we facing the same old-same old? PMID- 22071621 TI - The SOFFI Reference Guide: text, algorithms, and appendices: a manualized method for quality bottle-feedings. AB - The Support of Oral Feeding for Fragile Infants (SOFFI) method of bottle-feeding rests on quality evidence along with implementation details drawn from clinical experience. To be clear, the SOFFI Method is not focused on the amount of food taken in but on the conduct of the feeding and the development of competent infant feeding behavior that, consequently, assures the intake of food necessary for growth. The unique contribution of the SOFFI method is the systematic organization of scientific findings into clinically valid and reliable, easily followed algorithms, and a manualized Reference Guide for the assessments, decisions, and actions of a quality feeding.A quality feeding is recognized by a stable, self-regulated infant and a caregiver who sensitively (responsively) adjusts to the infant's physiology and behavior to realize an individualized feeding experience in which the infant remains comfortable and competent using his nascent abilities to ingest a comfortable amount of milk/formula. The SOFFI Reference Guide and Algorithms begin with prefeeding adjustments of the environment and follow step by step through a feeding with observations of specific infant behavior, decisions based on that behavior, and specific actions to safeguard emerging abilities and the quality of the experience. An important aspect the SOFFI Reference Guide and Algorithms is the clarity about pausing and stopping the feeding on the basis of the infant's physiology and behavior rather than on the basis of the amount ingested. The specificity of each observation, decision, and action enables nurses at all levels of experience to provide quality, highly individualized, holistic feedings. Throughout the course of feeding in the NICU, the nurse conveys to parents the integrated details (observations, decisions, and actions) particular to their infant, thus passing on the means for parents to become competent in quality feeding, to enjoy feeding time into the future, and to gain in confidence as they watch their infants grow. PMID- 22071623 TI - Gender, educational and age differences in meanings that underlie global self rated health. AB - OBJECTIVES: The single-item question on self-rated health has been widely used in surveys. This study aims to explore which frames of reference are used by respondents when answering this question, to describe differences in the used frame of reference according to gender, educational background and age, and to determine whether subgroup differences can be explained by differences in prior health experiences. METHODS: Face-to-face interviews were conducted in a sample of 310 adults who were asked to rate their health using a single-item question with closed-ended answering categories and to explain the reasons for the rating they gave with open-ended probes. Different indicators of prior health experiences were taken into account. RESULTS: Physical health problems were the most utilized referents. However, participants also mentioned reasons that go beyond the physical dimension of health. Subgroup differences were found. Prior health experiences partly explained subgroup differences for some referents, but not for others. CONCLUSIONS: Investigators using the single question on self rated health for comparing health across different population groups should be aware that the meaning of the question varies across different socio-demographic groups. PMID- 22071624 TI - The disposable soma theory revisited: time as a resource in the theories of aging. AB - All life processes are subject to time constraints. At the cellular level, damage repair and cell cycle arrest are interrelated, allowing sufficient time for repair prior to cell cycle progression. Organisms have evolved so that developmental timing is linked to environmental conditions, such as nutrient availability and predation. Recent results in mammals regarding species-specific differences in cell cycle arrest and DNA damage suggest that a stable cell cycle arrest is a feature of longer-lived species. The implication of these results is that longer-lived species delay cell cycle progression to a greater degree than shorter-lived species, allowing for higher fidelity repair. We suggest that the ability to devote longer periods of time to repair and maintenance is a key feature of longer-lived species, and that evolutionary pressure to complete repair and resume cell division is a determinant of species lifespan. Thus, time is a resource that must be managed by the organism to attempt to maximize the fidelity of repair while completing development and reproduction in the limited window of opportunity afforded by environmental pressures. This viewpoint on time as a resource has implications for theories regarding the aging process and the development of species lifespan. PMID- 22071625 TI - MET-dependent cancer invasion may be preprogrammed by early alterations of p53 regulated feedforward loop and triggered by stromal cell-derived HGF. AB - MET, a receptor protein tyrosine kinase activated by hepatocyte growth factor (HGF), is a crucial determinant of metastatic progression. Recently, we have identified p53 as an important regulator of MET-dependent cell motility and invasion. This regulation occurs via feedforward loop suppressing MET expression by miR-34-dependent and -independent mechanisms. Here, by using Dicer conditional knockout, we provide further evidence for microRNA-independent MET regulation by p53. Furthermore, we show that while MET levels increase immediately after p53 inactivation, mutant cells do not contain active phosphorylated MET and remain non-invasive for a long latency period at contrary to cell culture observations. Evaluation of mouse models of ovarian and prostate carcinogenesis indicates that formation of desmoplastic stroma, associated production of HGF by stromal cells and coinciding MET phosphorylation precede cancer invasion. Thus, initiation mutation of p53 is sufficient for preprogramming motile and invasive properties of epithelial cells, but the stromal reaction may represent a critical step for their manifestation during cancer progression. PMID- 22071626 TI - The centrosome and bipolar spindle assembly: does one have anything to do with the other? AB - In vertebrate somatic cells the centrosome functions as the major microtubule organizing center (MTOC), which splits and separates to form the poles of the mitotic spindle. However, the role of the centriole-containing centrosome in the formation of bipolar mitotic spindles continues to be controversial. Cells normally containing centrosomes are still able to build bipolar spindles after their centrioles have been removed or ablated. In naturally occurring cellular systems that lack centrioles - such as plant cells and many oocytes - bipolar spindles form in the complete absence of canonical centrosomes. These observations have led to the notion that centrosomes play no role during mitosis. However, recent work has re-examined spindle assembly in the absence of centrosomes, both in cells that naturally lack them, and those that have had them experimentally removed. The results of these studies suggest that an appreciation of microtubule network organization- both before and after nuclear envelope breakdown (NEB) - is the key to understanding the mechanisms that regulate spindle assembly and the generation of bipolarity. PMID- 22071627 TI - Ceramide triggers metacaspase-independent mitochondrial cell death in yeast. AB - The activation of ceramide-generating enzymes, the blockade of ceramide degradation, or the addition of ceramide analogues can trigger apoptosis or necrosis in human cancer cells. Moreover, endogenous ceramide plays a decisive role in the killing of neoplastic cells by conventional anticancer chemotherapeutics. Here, we explored the possibility that membrane-permeable C2 ceramide might kill budding yeast (Saccharomyces cerevisiae) cells under fermentative conditions, where they exhibit rapid proliferation and a Warburg like metabolism that is reminiscent of cancer cells. C2-ceramide efficiently induced the generation of reactive oxygen species (ROS), as well as apoptotic and necrotic cell death, and this effect was not influenced by deletion of the sole yeast metacaspase. However, C2-ceramide largely failed to cause ROS hypergeneration and cell death upon deletion of the mitochondrial genome. Thus, mitochondrial function is strictly required for C2-ceramide-induced yeast lethality. Accordingly, mitochondria from C2-ceramide-treated yeast cells exhibited major morphological alterations including organelle fragmentation and aggregation. Altogether, our results point to a pivotal role of mitochondria in ceramide-induced yeast cell death. PMID- 22071628 TI - Proteasome inhibitors suppress expression of NPM and ARF proteins. AB - Proteasome inhibitors stabilize numerous proteins by inhibiting their degradation. Previously we have demonstrated that proteasome inhibitors thiostrepton, MG132 and bortezomib paradoxically inhibit transcriptional activity and mRNA/protein expression of FOXM1. Here we demonstrate that, in addition to FOXM1, the same proteasome inhibitors also decrease mRNA and protein expression of NPM and ARF genes. These data suggest that proteasome inhibitors may suppress gene expression by stabilizing their transcriptional inhibitors. PMID- 22071629 TI - Developmental relationships between B-1 and B-2 progenitors. PMID- 22071630 TI - Neural correlates of giving support to a loved one. AB - OBJECTIVE: Social support may benefit mental and physical well-being, but most research has focused on the receipt, rather than the provision, of social support. We explored the potentially beneficial effects of support giving by examining the neural substrates of giving support to a loved one. We focused on a priori regions of interest in the ventral striatum and septal area (SA) because of their role in maternal caregiving behavior in animals. METHODS: Twenty romantic couples completed a functional magnetic resonance imaging session in which the female partner underwent a scan while her partner stood just outside the scanner and received unpleasant electric shocks. RESULTS: Support giving (holding a partner's arm while they experienced physical pain), compared with other control conditions, led to significantly more activity in the ventral striatum, a reward-related region also involved in maternal behavior (p values < .05). Similar effects were observed for the SA, a region involved in both maternal behavior and fear attenuation. Greater activity in each of these regions during support giving was associated with greater self-reported support giving effectiveness and social connection (r values = 0.55-0.64, p values < .05). In addition, in line with the SA's role in fear attenuation (presumably to facilitate caregiving during stress), increased SA activity during support giving was associated with reduced left (r = -0.44, p < .05) and right (r = -0.42, p < .05) amygdala activity. CONCLUSIONS: Results suggest that support giving may be beneficial not only for the receiver but also for the giver. Implications for the possible stress-reducing effects of support giving are discussed. PMID- 22071631 TI - Physiological regulation of MMPs and tPA/PAI in the arterial wall of rats by noradrenergic tone and angiotensin II. AB - The interactions between the sympathetic nervous system (SNS) and angiotensin II (ANG II), and their direct effects in vitro on the enzymes involved in vascular extracellular matrix (ECM) degradation, were examined. Rats were treated with guanethidine, losartan or the combined treatments. mRNA, protein and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and mRNA of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were quantified in abdominal aorta (AA) and femoral artery (FA). Norepinephrine (NE) or ANG II with adrenergic (beta, alpha1 and alpha2) or losartan antagonists was tested for MMP mRNA response in cultured vascular smooth muscle cells (VSMCs). Combined treatment enhances the inhibition of MMP-2 mRNA and protein level induced by simple treatment in AA. However MMP-9 in AA and MMP mRNA in FA were reduced in the same order by treatments. MMP activities were not affected by treatments. The t-PA/PAI-1 ratio, which reflects the fibrinolytic balance, remained higher after treatments. In cultured VSMCs, NE induced stimulation of MMP mRNA via alpha2 and beta adrenergic receptors and MMP-2 activity via beta adrenergic receptors, while ANG II-induced stimulation was abrogated by losartan. Overall, there is a synergic inhibition of both systems on the level of MMP-2 in AA. PMID- 22071632 TI - Mcl-1 levels need not be lowered for cells to be sensitized for ABT-263/737 induced apoptosis. PMID- 22071636 TI - Structures of medium sized tin cluster anions. AB - The structures of medium sized tin cluster anions Sn(n)(-) (n = 16-29) were determined by a combination of density functional theory, trapped ion electron diffraction and collision induced dissociation (CID). Mostly prolate structures were found with a structural motif based on only three repeatedly appearing subunit clusters, the Sn(7) pentagonal bipyramid, the Sn(9) tricapped trigonal prism and the Sn(10) bicapped tetragonal antiprism. Sn(16)(-) and Sn(17)(-) are composed of two face connected subunits. In Sn(18)(-)-Sn(20)(-) the subunits form cluster dimers. For Sn(21)(-)-Sn(23)(-) additional tin atoms are inserted between the building blocks. Sn(24)(-) and Sn(25)(-) are composed of a Sn(9) or Sn(10) connected to a Sn(15) subunit, which closely resembles the ground state of Sn(15)(-). Finally, in the larger clusters Sn(26)(-)-Sn(29)(-) additional bridging atoms again connect the building blocks. The CID experiments reveal fission as the main fragmentation channel for all investigated cluster sizes. This rather unexpected "pearl-chain" cluster growth mode is rationalized by the extraordinary stability of the building blocks. PMID- 22071634 TI - Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: involvement of AKT activation. AB - Several labdane diterpenes exert anti-inflammatory and cytoprotective actions; therefore, we have investigated whether these molecules protect cardiomyocytes in an anoxia/reperfusion (A/R) model, establishing the molecular mechanisms involved in the process. The cardioprotective activity of three diterpenes (T1, T2 and T3) was studied in the H9c2 cell line and in isolated rat cardiomyocyte subjected to A/R injury. In both cases, treatment with diterpenes T1 and T2 protected from A/R induced apoptosis, as deduced by a decrease in the percentage of apoptotic and caspase-3 active positive cells, a decrease in the Bcl-2/Bax ratio and an increase in the expression of antiapoptotic proteins. Analysis of cell survival signaling pathways showed that diterpenes T1 and T2 added after A/R increased phospho-AKT and phospho-ERK 1/2 levels. These cardioprotective effects were lost when AKT activity was pharmacologically inhibited. Moreover, the labdane-induced cardioprotection involves activation of AMPK, suggesting a role for energy homeostasis in their mechanism of action. Labdane diterpenes (T1 and T2) also exerted cardioprotective effects against A/R-induced injury in isolated cardiomyocytes and the mechanisms involved activation of specific survival signals (PI3K/AKT pathways, ERK1/2 and AMPK) and inhibition of apoptosis. PMID- 22071633 TI - Neurodegenerative processes in Huntington's disease. AB - Huntington's disease (HD) is a complex and severe disorder characterized by the gradual and the progressive loss of neurons, predominantly in the striatum, which leads to the typical motor and cognitive impairments associated with this pathology. HD is caused by a highly polymorphic CAG trinucleotide repeat expansion in the exon-1 of the gene encoding for huntingtin protein. Since the first discovery of the huntingtin gene, investigations with a consistent number of in-vitro and in-vivo models have provided insights into the toxic events related to the expression of the mutant protein. In this review, we will summarize the progress made in characterizing the signaling pathways that contribute to neuronal degeneration in HD. We will highlight the age-dependent loss of proteostasis that is primarily responsible for the formation of aggregates observed in HD patients. The most promising molecular targets for the development of pharmacological interventions will also be discussed. PMID- 22071637 TI - Antidiabetic plants of Iran. AB - To identify the antidiabetic plants of Iran, a systematic review of the published literature on the efficacy of Iranian medicinal plant for glucose control in patients with type 2 diabetes mellitus was conducted. We performed an electronic literature search of MEDLINE, Science Direct, Scopus, Proquest, Ebsco, Googlescholar, SID, Cochrane Library Database, from 1966 up to June 2010. The search terms were complementary and alternative medicine (CAM), diabetes mellitus, plant (herb), Iran, patient, glycemic control, clinical trial, RCT, natural or herbal medicine, hypoglycemic plants, and individual herb names from popular sources, or combination of these key words. Available Randomized Controlled Trials (RCT) published in English or Persian language examined effects of an herb (limited to Iran) on glycemic indexes in type 2 diabetic patients were included. Among all of the articles identified in the initial database search, 23 trials were RCT, examining herbs as potential therapy for type 2 diabetes mellitus. The key outcome for antidiabetic effect was changes in blood glucose or HbA(1) c, as well as improves in insulin sensitivity or resistance. Available data suggest that several antidiabetic plants of Iran need further study. Among the RCT studies, the best evidence in glycemic control was found in Citrullus colocynthus, Ipomoea betatas, Silybum marianum and Trigonella foenum graecum. PMID- 22071638 TI - Effects of continuous and interrupted forces on gene transcription in periodontal ligament cells in vitro. AB - The biological mechanisms of tooth movement are based on the response of periodontal tissues to mechanical forces. The final result of these responses is remodeling of the extracellular matrix. Tissue reactions may vary depending upon the type, magnitude and duration of the applied forces. The purpose of the present study was to analyze the effects of centrifugal force on the transcription of collagen type-I (Col-I), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase- 1 (TIMP-1) genes in human periodontal ligament (PDL) fibroblasts. Human fibroblasts obtained from the PDL were cultured and subjected to centrifugal forces (36.3 g/cm(2)) for 30, 60 and 90 min continuously. This was also carried out interruptedly, three times for 30 min and six times for 15 min. The mRNAs encoding for Col-I, MMP-1, and TIMP-1 were quantified using RT-PCR. The mRNA levels of Col-I and MMP-1 were increased when continuous force was applied for 30 min and 60 min respectively. The interrupted force had almost no effect on Col-I, MMP-1 and TIMP-1 genes. These results indicate that continuous forces may have a greater effect in inducing gene expression during the remodeling process of PDL compared to interrupted forces with short rest periods. PMID- 22071639 TI - Comparison of the results of Cox proportional hazards model and parametric models in the study of length of stay in a tertiary teaching hospital in Tehran, Iran. AB - Survival analysis is a set of methods used for analysis of the data which exist until the occurrence of an event. This study aimed to compare the results of the use of the semi-parametric Cox model with parametric models to determine the factors influencing the length of stay of patients in the inpatient units of Women Hospital in Tehran, Iran. In this historical cohort study all 3421 charts of the patients admitted to Obstetrics, Surgery and Oncology units in 2008 were reviewed and the required patient data such as medical insurance coverage types, admission months, days and times, inpatient units, final diagnoses, the number of diagnostic tests, admission types were collected. The patient length of stay in hospital 'leading to recovery' was considered as a survival variable. To compare the semi-parametric Cox model and parametric (including exponential, Weibull, Gompertz, log-normal, log-logistic and gamma) models and find the best model fitted to studied data, Akaike's Information Criterion (AIC) and Cox-Snell residual were used. P<0.05 was considered as statistically significant. AIC and Cox-Snell residual graph showed that the gamma model had the lowest AIC (4288.598) and the closest graph to the bisector. The results of the gamma model showed that factors affecting the patient length of stay were admission day, inpatient unit, related physician specialty, emergent admission, final diagnosis and the number of laboratory tests, radiographies and sonographies (P<0.05). The results showed that the gamma model provided a better fit to the studied data than the Cox proportional hazards model. Therefore, it is better for researchers of healthcare field to consider this model in their researches about the patient length of stay (LOS) if the assumption of proportional hazards is not fulfilled. PMID- 22071640 TI - Renal power Doppler ultrasonographic evaluation of children with acute pyelonephritis. AB - Urinary tract infections are common in children. The available gold standard method for diagnosis, Tc-99m dimercaptosuccinic acid scan is expensive and exposes patients to considerable amount of radiation. This study was performed to compare and assess the efficacy of Power Doppler Ultrasound versus Tc-99m DMSA scan for diagnosis of acute pyelonephritis. A quasi experimental study was conducted on 34 children with mean age of 2.8 +/- 2.7 years who were hospitalized with their first episode of febrile urinary tract infection. All children were evaluated in the first 3 days of admission by Doppler Ultrasound and Tc-99m DMSA scan. Patients with congenital structural anomalies were excluded. Each kidney was divided into three zones. The comparison between efficacy of Doppler Ultrasound and DMSA scan was carried out based on number of patients and on classified renal units. Based on the number of patients enrolled; the sensitivity, specificity, positive and negative predictive values and accuracy of Doppler Ultrasound were 89%, 53%, 70%, 80% and 74%, respectively but based on the renal units, it was 66%, 81%, 46%, 91% and 79% , respectively. Although Doppler Ultrasound has the potential for identifying acute pyelonephritis in children, but it is still soon to replace DMSA scan. PMID- 22071641 TI - Role of liver function enzymes in diagnosis of choledocholithiasis in biliary colic patients. AB - Liver functional tests due to inflammatory process which induced by cholecystitis might changed and some clinicians suggested that these changes might help us to stone prediction in common bile ducts and decrease hazards of performing ERCP and other invasive procedures. Present study was performed for assessment of role of liver functional test in diagnosis of common bile duct stone in patients with cholecystitis and help in their management. Present prospective study was performed between April 2010 and March 2011 on 350 patients who come to our hospital with cholecystitis or biliary colic diagnosis. Patients with cholesistitis diagnosis were underwent operation for removing gall bladder stone and retrograde cholangiopancreatography (ERCP) was performed for patients with suspicious to biliary colic and common bile duct (CBD) stones. Ultrasonography, aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP) and direct and total serum bilirubin were measured for all of participated patients. Mean of AST. ALT, ALP and total and direct bilirubin were had no significant differences between two study groups. In logistic regression analysis, after entering into the model only CBD diameter (OR: 20; P=0.00) and elevated serum level of ALT (OR: 2; P=0.04) were remained into the model and were known as independent predictor of cholelithiasis. Elevated level of liver enzymes had not main role in CBD diagnosis and ERCP had no to perform for suspicious CBD stone only with elevated liver enzyme and even with normal ultrasonography findings. Endosonography as non invasive procedure recommend for patients before ERCP. PMID- 22071643 TI - Characterization of anticancer, antimicrobial, antioxidant properties and chemical compositions of Peperomia pellucida leaf extract. AB - Peperomia pellucida leaf extract was characterized for its anticancer, antimicrobial, antioxidant activities, and chemical compositions. Anticancer activity of P. pellucida leaf extract was determined through Colorimetric MTT (tetrazolium) assay against human breast adenocarcinoma (MCF-7) cell line and the antimicrobial property of the plant extract was revealed by using two-fold broth micro-dilution method against 10 bacterial isolates. Antioxidant activity of the plant extract was then characterized using alpha, alpha-diphenyl-beta picrylhydrazyl (DPPH) radical scavenging method and the chemical compositions were screened and identified using gas chromatography-mass spectrometry (GC-MS). The results of present study indicated that P. pellucida leaf extract possessed anticancer activities with half maximal inhibitory concentration (IC(50)) of 10.4 +/- 0.06 ug/ml. The minimum inhibitory concentration (MIC) values were ranged from 31.25 to 125 mg/l in which the plant extract was found to inhibit the growth of Edwardsiella tarda, Escherichia coli, Flavobacterium sp., Pseudomonas aeruginosa and Vibrio cholerae at 31.25 mg/l; Klebsiella sp., Aeromonas hydrophila and Vibrio alginolyticus at 62.5 mg/l; and it was able to control the growth of Salmonella sp. and Vibrio parahaemolyticus at 125 mg/l. At the concentration of 0.625 ppt, the plant extract was found to inhibit 30% of DPPH, free radical. Phytol (37.88%) was the major compound in the plant extract followed by 2-Naphthalenol, decahydro- (26.20%), Hexadecanoic acid, methyl ester (18.31%) and 9,12-Octadecadienoic acid (Z,Z)-, methyl ester (17.61%). Findings from this study indicated that methanol extract of P. pellucida leaf possessed vast potential as medicinal drug especially in breast cancer treatment. PMID- 22071642 TI - Determination of trace elements in patients with chronic hepatitis B. AB - Chronic hepatitis B virus (HBV) infection is a major liver disease worldwide and its clinical manifestations are linked to immune response. The purpose of this study was to evaluate the relationship between selenium, copper, and zinc in comparison with transaminase level in chronic HBV patients. Serum samples of the HBV infected patients were obtained from Tooba medical center, Sari, Iran. Sixty patients were enrolled in this study (36 men and 24 women), mean age: 39.6 +/- 12.2 years. The concentration of zinc, selenium, copper and transaminases were determined using an autoanalyzer system. Concentrations of selenium (0.273 +/- 0.056 MUg/dl) and zinc (2.1 +/- 0.037) was elevated in patients with low transaminase levels as were significantly different in comparison with patients with high transaminase level (P<0.05). Serum copper concentration was similar in two groups of patients. Elevated levels of transaminase concentrations were independently associated with low zinc and selenium concentrations in chronic HBV patients. It is concluded that serum zinc and selenium levels are associated with less hepatic damage in chronic HBV patients and might have a protective role during liver injury. PMID- 22071644 TI - Characterization of Pseudomonas aeruginosa strains isolated from burned patients hospitalized in a major burn center in Tehran, Iran. AB - Pseudomonas aeruginosa is an important life-threatening nosocomial pathogen and plays a prominent role in serious infections in burned patients. The current study was undertaken to characterize P. aeruginosa strains isolated from burned patients in Tehran, Iran. The study was conducted in a major burn center in Tehran, Iran in 2007. A total of seventy specimens obtained from different clinical origin with positive culture results for P. aeruginosa were included in the study. Antimicrobial susceptibility test was performed according to the standard CLSI guideline. The relationship between the strains was also determined using antimicrobial drug resistance pattern analysis and plasmid profiling. All strains were multi drug resistant. The percentage of resistance to tested antibiotics was: imipenem 97.5%, amikacin 90%, piperacillin 87.5%, ceftizoxime 72.7%, gentamicin 67.5%, ciprofloxacin 65%, ceftriaxone 60%, and ceftazidime 57.5%. Thirteen resistant phenotypes were recognized, R3 (TET, IPM, AMK, CIP, PIP, GM, CAZ, CRO, CT) was the predominant resistance pattern seen in 27.5% of isolates. Results obtained from E-test showed that 100% of P. aeruginosa strains were resistant to cefoxitin, 97% to cefotetan, 93% to ticarcillin, 89% to ticarcillin/clav, 76% to gentamicin and imipenem, 63% to piperacillin, 49% to tetracycline, and 20% to meropenem. Nine different plasmid profiles were observed among the strains. The current study showed an increase rate of resistance for some antibiotics tested among P. aeruginosa strains isolated from burned patients in Tehran. A combination of antibiotic susceptibility testing and profile plasmid analysis, which are relatively cheap and available methods, showed to be useful to characterize the clinical strains of P. aeruginosa isolated from burned patients in Iran. PMID- 22071645 TI - Prevalence rates of obsessive-compulsive symptoms and psychiatric comorbidity among adolescents in Iran. AB - Recent epidemiological studies show that obsessive-compulsive disorder (OCD) and its comorbidity with psychiatric problems is more prevalent among children and adolescents than was previously believed. The primary aim of the current study is to investigate the point-prevalence rate of obsessive compulsive symptoms in a sample of adolescent high school student in Iran. A two-stage epidemiological study was carried out through a clustered random sampling method. All participants went through a two-stage assessment procedure, in the first screening phase, the Maudsley Obsessive-Compulsive Inventory (MOCI) was administered to 909 randomly selected students (in the age range 14-18 years). Participants were considered possible sub-clinical or clinical OCD cases, if they obtained a score of MOCI>=15. In the second stage, the Symptoms Checklist -90 revised (SCL-90-R) was administered to student who fulfilled the screening criteria. The prevalence of OC symptoms was found to be 11.2 percent for the total sample. The most prevalent comorbid conditions were depression and anxiety with prevalence rates of 91.2 and 78.4 percent respectively. Gender, age, birth order, parent's education and family income had no statistically significant association with OC symptoms. Further research in this area is warranted in order to establish a set of comprehensive global assessment and measurement tools, which would allow cross-cultural studies in the field of OCD. PMID- 22071646 TI - A bulking agent may lead to adrenal insufficiency crisis: a case report. AB - Adrenal insufficiency is a life-threatening disorder which must be treated with glucocorticoid replacement and needs permanent dose adjustment during patient's different somatic situations. Insufficient glucocorticoid doses result in adrenal crisis and must be treated with intravenous hydrocortisone. The patient was known with Adrenal insufficiency and was treated optimally with fludrocortisone and prednisolone since seven years with no history of adrenal crisis. The patient was admitted with abdominal pain, weakness, fatigue and nausea developed 3-4 days after taking psyllium, a bulking agent, prescribed by a surgeon to diagnose anal fissure. Detailed medical history, physical examinations, laboratory and imaging examinations did not approve any other cause of adrenal crisis. Psyllium may interfere with gastrointestinal absorption of prednisolone and/or fludrocortisone and trigger acute adrenal crisis in patients with adrenal insufficiency. PMID- 22071647 TI - Large omental cyst: a case report and review of the literature. AB - Omental cysts occur rarely. Patients with omental cysts usually present with abdominal distention and a painless abdominal mass. In children it may present as an acute abdomen due to intestinal obstruction. The most common physical finding of an omental cyst is a freely movable abdominal mass, which should be considered in differential diagnosis of these cases. The diagnostic procedures include ultrasonography and computed tomography (CT) scans. Complete excision of the cyst is considered as the treatment of choice. Recurrence and malignant deterioration of omental cysts are rare. We describe a 32- year-old female who presented with complaints of vague abdominal pain and distension. The patient underwent laparotomy with preoperative diagnosis of the ovarian cyst. The diagnosis of omental cyst was established by intraoperative findings. Thus, complete excision of the cyst was performed. The diagnosis was confirmed by pathological examination. PMID- 22071648 TI - Primary bilateral intrapelvic hydatid cyst presenting with adnexal cystic mass: a case report. AB - Hydatid disease, caused by Echinococcus granulosus, is a common parasitic infection of the liver. Disseminated intra-abdominal hydatid disease may occur with the rupture of the hydatid cyst into the peritoneal cavity, producing secondary echinococcosis. But primary hydatid cyst in the pelvis is rare. We report a case of bilateral hydatid cyst of the pelvis in a 53 years old woman presented with adnexal cystic mass. PMID- 22071649 TI - Lumbar vertebral hemangioma with extradural extension, causing neurogenic claudication: a case report. AB - The authors present a rare case of lumbar vertebral hemangioma extending to the epidural space with a bisected appearance and impinging on thecal sac. This 52 year-old lady presented with one year history of low back pain and bilateral leg radiation. Plain radiography showed vertical linear streaks at L2 vertebral body and axial computed tomography (CT) scan revealed small "polka dot" appearance within the vertebral body. Magnetic resonance imaging (MRI) showed low signal intensity on T1-weighted images in L2 vertebral body which was not characteristic for hemangioma. The patient underwent an L2 laminectomy, spinal canal decompression and posterior spinal instrumentation. This study indicates that lumbar vertebral hemangioma can extend to the epidural space and cause neurologic symptoms. Magnetic resonance imaging may not show diagnostic features, especially in active lesions and plain radiography and CT scan may be helpful. PMID- 22071650 TI - Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. AB - BACKGROUND: Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care. METHODS: We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping. RESULTS: Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had >=1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and beta-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy. CONCLUSIONS: Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice. PMID- 22071651 TI - A new method for choosing the computational cell in stochastic reaction-diffusion systems. AB - How to choose the computational compartment or cell size for the stochastic simulation of a reaction-diffusion system is still an open problem, and a number of criteria have been suggested. A generalized measure of the noise for finite dimensional systems based on the largest eigenvalue of the covariance matrix of the number of molecules of all species has been suggested as a measure of the overall fluctuations in a multivariate system, and we apply it here to a discretized reaction-diffusion system. We show that for a broad class of first order reaction networks this measure converges to the square root of the reciprocal of the smallest mean species number in a compartment at the steady state. We show that a suitably re-normalized measure stabilizes as the volume of a cell approaches zero, which leads to a criterion for the maximum volume of the compartments in a computational grid. We then derive a new criterion based on the sensitivity of the entire network, not just of the fastest step, that predicts a grid size that assures that the concentrations of all species converge to a spatially-uniform solution. This criterion applies for all orders of reactions and for reaction rate functions derived from singular perturbation or other reduction methods, and encompasses both diffusing and non-diffusing species. We show that this predicts the maximal allowable volume found in a linear problem, and we illustrate our results with an example motivated by anterior-posterior pattern formation in Drosophila, and with several other examples. PMID- 22071653 TI - A finite-element model for healing of cutaneous wounds combining contraction, angiogenesis and closure. AB - A simplified finite-element model for wound healing is proposed. The model takes into account the sequential steps of dermal regeneration, wound contraction, angiogenesis and wound closure. An innovation in the present study is the combination of the aforementioned partially overlapping processes, which can be used to deliver novel insights into the process of wound healing, such as geometry related influences, as well as the influence of coupling between the various existing subprocesses on the actual healing behavior. The model confirms the clinical observation that epidermal closure proceeds by a crawling and climbing mechanism at the early stages, and by a stratification process in layers parallel to the skin surface at the later stages. The local epidermal oxygen content may play an important role here. The model can also be used to investigate the influence of local injection of hormones that stimulate partial processes occurring during wound healing. These insights can be used to improve wound healing treatments. PMID- 22071654 TI - The hydra effect, bubbles, and chaos in a simple discrete population model with constant effort harvesting. AB - We analyze the effects of a strategy of constant effort harvesting in the global dynamics of a one-dimensional discrete population model that includes density independent survivorship of adults and overcompensating density dependence. We discuss the phenomenon of bubbling (which indicates that harvesting can magnify fluctuations in population abundance) and the hydra effect, which means that the stock size gets larger as harvesting rate increases. Moreover, we show that the system displays chaotic behaviour under the combination of high per capita recruitment and small survivorship rates. PMID- 22071655 TI - An interaction stress analysis of nanoscale elastic asperity contacts. AB - A new contact mechanics model is presented and experimentally examined at the nanoscale. The current work addresses the well-established field of contact mechanics, but at the nanoscale where interaction stresses seem to be effective. The new model combines the classic Hertz theory with the new interaction stress concept to provide the stress field in contact bodies with adhesion. Hence, it benefits from the simplicity of non-adhesive models, while offering the same applicability as more complicated models. In order to examine the model, a set of atomic force microscopy experiments were performed on substrates made from single walled carbon nanotube buckypaper. The stress field in the substrate was obtained by superposition of the Hertzian stress field and the interaction stress field, and then compared to other contact models. Finally, the effect of indentation depth on the stress field was studied for the interaction model as well as for the Hertz, Derjaguin-Muller-Toporov, and Johnson-Kendall-Roberts models. Thus, the amount of error introduced by using the Hertz theory to model contacts with adhesion was found for different indentation depths. It was observed that in the absence of interaction stress data, the Hertz theory predictions led to smaller errors compared to other contact-with-adhesion models. PMID- 22071660 TI - Analgesic and anti-inflammatory effect of aqueous extract of the stem bark of Allanblackia gabonensis (Guttiferae). AB - Allanblackia gabonensis (Guttiferae) is a plant used in the African traditional medicine as remedies against pain, rheumatism, inflammations. In the present work, the analgesic effect of aqueous extract has been evaluated using acetic acid, formalin, hot-plate test, tail immersion and paw-pressure test. The anti inflammatory effect of this extract was also investigated on carrageenan, histamine or serotonin induced by paw oedema. Aqueous extract of stem bark of A. gabonensis administrated p.o. showed significant activity against paw oedema induced by carrageenan, with a maximum percentage of inhibition reaching the 74.01% at the preventive test at a dose of 200 mg/kg. A. gabonensis exhibited a significant reduction of paw oedema induced by both histamine and serotonin with a maximal inhibition of 56.94% (200 mg/kg) and 40.83% (100 mg/kg), respectively. It showed significant protective effects against chemical stimuli (acetic acid and formalin) in the mouse. Administered orally at the doses of 100-400 mg/kg, exhibited protective effect of at least 69.78% on the pain induced by acetic acid and also reduced first (67.18% at 200 mg/kg) and second (83.87% at 400 mg/kg) phase of pain-induced par formalin. It also produced a significant increase of the threshold of sensitivity to pressure and hot plate-induced pain in the rats. These results suggest a peripheral and central analgesic activities as well as an anti-inflammatory effect of the stem bark of A. gabonensis. PMID- 22071661 TI - Are Th17 cells in the gut pathogenic or protective? AB - Th17 cells are abundant in multiple chronic inflammatory and autoimmune diseases. Clinical trials with antibodies to interleukin (IL)-17A, one of the Th17-cell signature cytokines, have recently reported therapeutic benefit in multiple patient populations; however, in Crohn's disease the role of Th17 cells and IL 17A appears to be more complicated. The development of different subsets of Th17 cells and their relative pathogenic activities with a focus on the gut environment will be discussed. PMID- 22071662 TI - Voriconazole, combined with amphotericin B, in the treatment for pulmonary cryptococcosis caused by C. neoformans (serotype A) in mice with severe combined immunodeficiency (SCID). AB - Cryptococcosis is a subacute or chronic systemic mycosis with a cosmopolitan nature, caused by yeast of the genus Cryptococcus neoformans. The model of systemic cryptococcosis in mice with severe combined immunodeficiency (SCID) is useful for immunological and therapeutic study of the disease in immunodeficient hosts. Amphotericin B, fluconazole and flucytosine are the drugs most commonly used to treat cryptococcosis. Voriconazole is a triazole with high bioavailability, large distribution volume, and excellent penetration of the central nervous system. The objective of this study was to evaluate treatment with amphotericin B (AMB), voriconazole (VRC), and AMB, used in combination with VRC, of experimental pulmonary cryptococcosis in a murine model (SCID). The animals were inoculated intravenously (iv) with a solution containing 3.0 * 10(5) viable cells of C. neoformans ATCC 90112, (serotype A). Treatments were performed with amphotericin B (1.5 mg/kg/day), voriconazole (40.0 mg/kg/day) and AMB (1.5 mg/kg/day) combined with VRC (40.0 mg/kg/day); began 1 day after the initial infection; were daily; and lasted 15 days. Evaluations were performed using analysis of the survival curve and isolation of yeast in the lung tissue. There was a significant increase in survival in groups treated with AMB combined with VRC, compared with the untreated group and groups receiving other treatments (P < 0.05). In the group treated only with VRC and AMB combined with VRC, there was a significant reduction (P < 0.05) in the isolation of C. neoformans in lung tissue. Amphotericin B combined with voriconazole may be an effective alternative to increasing survival and may reduce yeast in the lung tissue of mice with pulmonary cryptococcosis and SCID. PMID- 22071663 TI - Extra-scalp black dot ringworm caused by Trichophyton tonsurans among contact sports players. AB - We describe here two patients with tinea corporis exhibiting black dot ringworm (BDR). A cluster of black dots was observed on the extensor surfaces of the extremities of two rather hairy male patients, a 15-year-old judo practitioner and a 26-year-old combined martial arts fighter, during treatment of tinea corporis with topical antimycotics. Direct KOH examination showed that the black dots were composed of degenerated hair with numerous arthroconidia and were indistinguishable from BDR of tinea capitis. Trichophyton tonsurans was isolated from the dots of both patients. Although they were diagnosed with tinea corporis, they required 2-3 months of treatment with oral terbinafine. Dermatologists should be aware that BDR can appear on areas of the skin other than the scalp. PMID- 22071665 TI - Preliminary assessment of ecological exposure of adult residents in Fukushima Prefecture to radioactive cesium through ingestion and inhalation. AB - OBJECTIVE: This study aims to estimate the ecological exposure of adult residents of Fukushima Prefecture to 134cesium (Cs) and 137Cs through ingestion and inhalation between July 2 and July 8, 2011. METHODS: Fifty-five sets of meals with tap water, each representing one person's daily intake, were purchased in local towns in Fukushima Prefecture. Locally produced cow's milk (21 samples) and vegetables (43 samples) were also purchased. In parallel, air sampling was conducted at 12 different sites using a high-volume sampler. Nineteen sets of control meals were collected in Kyoto in July 2011. 134Cs and 137Cs levels in the samples were measured using a germanium detector. RESULTS: Radioactivity was detected in 36 of the 55 sample meals from Fukushima, compared with one of 19 controls from Kyoto. The median estimated dose level (MUSv/year) was 3.0, ranging from not detectable to 83.1. None of the cow's milk (21) or vegetable (49) samples showed levels of contamination above the current recommended limits (Bq/kg) of 200 for milk and 500 for vegetables. The total effective dose levels by inhalation were estimated to be <3 MUSv/year at nine locations, but samples at three other locations close to the edge of the 20-km radius from the crippled nuclear power plant showed higher levels of contamination (MUSv/year): 14.7 at Iitate, 76.9 at Namie, and 27.7 at Katsurao. CONCLUSIONS: Levels of exposure to 134Cs and 137Cs in Fukushima by ingestion and inhalation are discernible, but generally within recommended limits. PMID- 22071666 TI - [Quality indicators of drug therapy at hospital admission among elderly patients]. AB - OBJECTIVE: Increased morbidity and higher prevalence of medication use commonly coexists among the elderly. When managed appropriately, older patients can benefit from drug therapy. However, drug related problems are more frequent and more serious in the elderly. The aim of the study was to assess the quality of medication use in older people at hospital admission. MATERIAL AND METHODS: A retrospective medical record review was performed for patients 70 years and older who had an unplanned admission to the internal medicine and geriatric units at Landspitali University Hospital in 2007. Among the sampled medical records, 913 met inclusion criteria. Assessment was carried out using 15 drug-specific quality indicators. RESULTS: Mean age was 80.9 years and 54.5% were women. Mean number of drugs at admission was 7.0 for women and 6.5 for men (p=0.047). The prevalence of having one or more quality indicators on admission was 48.4%. Women were more likely to have a quality indicator than men (women 56.2%, men 39.9%). The probability also increased with increasing age and number of drugs. CONCLUSIONS: The quality of drug therapy among older patients at hospital admission appears to be suboptimal. A more accurate estimate of the problem could be obtained through a prospective study where drug regimens are correlated with symptoms and reason for admission. Additional studies are also needed in the outpatient setting. Such studies could provide more accurate evidence and assist policy making towards improved quality of drug prescribing for a growing number of older patients. KEYWORDS: elderly, quality indicators, hospitalization, drugs, inappropriate prescribing. PMID- 22071667 TI - [Efficacy of cognitive behavioral therapy in the treatment of mood and anxiety disorders in adults]. AB - Cognitive behavioral therapy (CBT) represents that form of psychotherapy which has most research data to build on in the treatment of mood and anxiety disorders for adults. In this review we will introduce CBT and present the results of pertinent outcome research. Efficacy at the end of treatment is discussed, as well as long term effectiveness and the efficacy of combined treatment with medication and CBT. In addition, we discuss the pros and cons of group CBT compared to CBT in individual format, and comorbidity of mental disorders. According to this review CBT is efficacious for major depressive disorder, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive compulsive disorder, social phobia and specific phobia. Efficacy of CBT is equal to or better than efficacy of drugs in the treatment of the above disorders, but there is less access to CBT. Longterm effectiveness of CBT appears to be good, but research on combined treatment is yet in its infancy and conclusions are premature on its place in treatment. Key words: Cognitive behavioral therapy, psychotropic treatment, efficacy, long-term effects, combined treatment, mental disorders, adults. PMID- 22071668 TI - [Landspitali, national university hospital, cuts or rationalization?]. PMID- 22071669 TI - [The United Nations and non-communicable diseases]. PMID- 22071670 TI - [Aortic valve replacement for aortic stenosis in Iceland 2002-2006: Long term complications and survival]. AB - OBJECTIVE: To investigate long-term complications and survival following aortic valve replacement (AVR) in patients with aortic stenosis (AS) in Iceland. MATERIAL AND METHODS: Included were 156 patients (average age 71.7 yrs, 64.7% males) that underwent AVR for AS at Landspitali between 2002 and 2006. A mechanical prosthesis was used in 29 patients (18.6%) and a bioprosthesis in 127. Long-term complications and operation-related admissions were registered from hospital and outpatient records until April 1, 2010. Overall survival was estimated and compared with the Icelandic population of the same age and gender. RESULTS: The mean preop. EuroSCORE(st) was 6.9%, the max. transvalvular pressure gradient 74.1 mmHg and the left ventricular ejection fraction (LVEF) (57.2%). At six months following AVR the maximal pressure gradient was 19.8 mmHg (range; 2.5 38). Echocardiography results were not available for 23.6% of the patients 6 months postoperatively. In the follow-up period one in four patients was admitted due to valve-related problems. Re-admission rate was 6.0/100 patient-years (pt y); most commonly due to cardiac failure (1.7/100 pt-y), emboli (1.6/100 pt-y), hemorrhage (1.6/100 pt-y), endocarditis (0.7/100 pt-y) and myocardial infarction (0.4/100 pt-y). Survival at 1 and 5 year was 89.7% and 78.2%, respectively, making survival comparable to the estimated survival of Icelanders of the same age and gender. CONCLUSIONS: The rate of long-term complications following AVR in Iceland is in line with other studies. The same applies to long-term survival, which was similar to that of the Icelandic population of the same age and gender. Key words: Aortic valve replacement, aortic stenosis, heart surgery, results, long-term complication, survival. PMID- 22071671 TI - [Health-related quality of life during a clinical behavior weight loss intervention therapy]. AB - INTRODUCTION: The aim of this study was to assess the effect of a multidisciplinary, behavioural obesity treatment program on weight management, physical improvements and health-related quality of life. MATERIAL AND METHODS: The participants counted 47 women aged 20-60 years. The measurement period was from October 2007-July 2009 and a median time between measurements was six months. MEASUREMENTS: height (cm), weight (kg), body mass index (BMI), waist circumference (WC), bioelectrical impedance analysis (BIA), cycle ergometer fitness test (w/kg), electrocardiogram, maximal oxygen uptake (VO2max), blood pressure (mmHg) and heart rate (bpm). Different dimensions of mental and physical health were assessed using validated questionnaires: SF-36v2TM of health-related quality of life, OP scale of psychosocial functioning in the obese, BAI anxiety inventory scale and BDI-II depression inventory scale. RESULTS: BMI decreased on average by 3.9 kg/m2 (p<0.001). The total maximum output (watts) during the fitness test increased on average by 12% (p<0.001), fitness (w/kg) increased by 21% (p<0.001) and VO2max (ml/kg/min) by 18% (p<0.001). A decrease was noted in blood pressure as well as resting heart rate (p<0.05) at the end of the program. The results from the questionnaires showed improvements in quality of life and psychological well being (p<0.001). CONCLUSION: These results highlight the importance of comprehensive weight management and emphasize the importance of permanent lifestyle changes for the patients. KEYWORDS: Obesity, women, behavior therapy, ergometric. PMID- 22071672 TI - Maternal inheritance of plastids and mitochondria in Cycas L. (Cycadaceae). AB - Cycas is often considered a living fossil, thereby providing a unique model for revealing the evolution of spermatophytes. To date, the genetic inheritance of these archaic plants is not fully understood. The present study seeks to document the process of organelle inheritance in an interspecific cross of Cycas species. Extranuclear organelle DNA from chloroplasts and mitochondria was analyzed using both polymerase chain reaction-restriction fragment length polymorphism analysis and microscopy. Here, we show that the chloroplasts and mitochondria in the progeny of interspecific crosses between Cycas taitungensis and Cycas ferruginea were exclusively inherited from the female parent. Epifluorescence microscopic analyses of the pollen cells from Cycas elongata indicated that there was a significant degradation of organelle DNA in male reproductive cells following maturation; the DNA fluorescent signals were only seen after pollen mitosis two, but not detectable at mature stage. Lack of organelle DNA fluorescent signal in prothallial cells was confirmed by the absence of plastids and mitochondria in electronic microscopic images. In conclusion, these data suggest that the maternal plastid and mitochondrial inheritance in Cycas, native to the old world, are the same as seen in seed plants. PMID- 22071674 TI - Accuracy of non-ECG-gated computed tomography angiography of the chest in assessment of left-sided cardiac chamber enlargement. AB - PURPOSE: To determine whether measurement of left ventricular (LV) and left atrial (LA) diameters on nongated computed tomography angiography (CTA) can detect left atrial and left ventricular enlargement (LAE and LVE) with high specificity. MATERIALS AND METHODS: Ninety-nine patients who had undergone both nongated CTA of the chest and echocardiography within 1 week constituted the pilot group. On CTA, LA and LV diameters were measured in the axial plane and on a 3-chamber-view multiplanar reconstruction. These measurements were compared with echocardiography results. Receiver operating characteristic (ROC) curves were then generated to determine optimal cutoff values for diagnosis of LAE and LVE. These thresholds were applied to a validation group (n = 203), and sensitivities and specificities for cutoff values were determined. Simple kappa coefficients were calculated for interobserver agreement. RESULTS: In the pilot group, axial measurements of the LA and LV diameters were superior to multiplanar reconstruction measurements based on areas under the ROC (LV: 0.82 vs. 0.76, LA: 0.87 vs. 0.82). Using the ROC results, cutoff values of 5.5 and 4.5 cm were chosen for LVE and LAE, respectively. These thresholds were applied to the validation group, achieving an average sensitivity and specificity for LAE of 53% [confidence interval (CI): 37%-71% and 94% (89%-97%)], respectively. Average sensitivity and specificity for LVE were 41% (CI: 23%-59%) and 99% (CI: 96% 100%), respectively. Kappa coefficients for diagnosis of LAE and LVE were 0.70 and 0.81, respectively. CONCLUSION: Thresholds for LA and LV diameter on nongated CTA can be chosen to provide specific, but not sensitive, detection of LAE and LVE. PMID- 22071673 TI - Differential contributions of impaired corneal sensitivity and reduced tear secretion to corneal epithelial disorders. AB - BACKGROUND/AIMS: To determine the possible roles of impaired corneal sensitivity and reduced tear secretion in various types of corneal epithelial disorders. METHODS: A total of 99 patients (179 eyes) with corneal epithelial disorders classified as persistent epithelial defects (PED), corneal erosion, or superficial punctate keratopathy (SPK) and 115 individuals (230 eyes) without apparent ocular surface disorders (controls) were enrolled in a prospective study. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer, and tear secretion was measured by the Schirmer test in each subject. RESULTS: Corneal sensitivity of eyes in the PED and corneal erosion groups was significantly lower than that in the control group. Schirmer test values for eyes in the SPK group were significantly reduced compared with those in the control group. CONCLUSION: A loss of corneal sensitivity may contribute to the development of PED and corneal erosion, whereas reduced tear secretion may be a contributing factor for SPK. Both results indicate the importance of corneal sensory innervation to the maintenance of corneal integrity. PMID- 22071675 TI - Limited, fast magnetic resonance imaging as an alternative for preoperative evaluation of pectus excavatum: a feasibility study. AB - OBJECTIVE: The purpose of this study was to determine the reliability, feasibility, and image quality of a limited, fast magnetic resonance imaging (MRI) protocol for preoperative evaluation of pectus excavatum in a pediatric population referred for presurgical imaging. MATERIALS AND METHODS: A total of 47 patients, median age 14 years, referred for preoperative imaging of pectus excavatum, underwent axial balanced steady-state free precession MRI of the chest, with a limited patient charge. Two pediatric radiologists independently conducted a blinded retrospective study. The Haller and asymmetry indices were calculated at the level of greatest anterior-posterior chest narrowing. In addition, right heart compression and image quality were subjectively assessed, and scan duration was determined. RESULTS: Intraclass correlation coefficient reliability was between 0.85 and 0.98, indicating almost perfect agreement for quantitative measurements. Subjective evaluation of right heart compression and image quality showed moderate interreader agreement. Image quality was graded as good or excellent by both readers for all studies. No difference in the Haller index was observed between modalities in 3 patients on both computed tomographic scan and MRI (P = 0.2697). The median scan duration was 8 minutes. CONCLUSIONS: Limited MRI is a reliable and cost-effective alternative for preoperative assessment of pectus excavatum. It is fast, free of ionizing radiation, and there is excellent interreader reliability for measurements of chest wall deformity. PMID- 22071676 TI - Angiomyolipomas of the mediastinum and the lung. AB - Angiomyolipomas are benign neoplasms composed of various tissues, including components of fat, abnormal blood vessels, and smooth muscle cells. They most commonly occur in the kidney, but on rare occasions they occur in extrarenal sites. We present a case of angiomyolipomas in the mediastinum and lung, possibly associated with lymphangioleiomyomatosis and tuberous sclerosis complex. PMID- 22071677 TI - High-resolution computed tomography findings in a case of severe leptospira infection (Weil disease) complicated with Jarisch-Herxheimer reaction. AB - In this report, we describe a case of Weil disease. Chest x-ray and computed tomography (CT) findings showed temporary deterioration 1 day after the initiation of antibiotic treatment, and high-resolution CT findings with the patient's physical findings made us suspect pulmonary alveolar hemorrhage (PAH). We believed that the PAH had been induced by Weil disease and subsequently caused Jarisch-Herxheimer reaction. We confirmed the patient's contact history with mice, and symptoms improved immediately after starting appropriate treatments. Leptospirosis is a relatively rare cause of PAH. Therefore, the possibility of this disease should be included in the differential diagnosis, especially when high-resolution CT findings indicate PAH, and the imaging findings deteriorate rapidly after antibiotic therapy. PMID- 22071678 TI - Witnessed pulmonary vein arrest-endoscopically observed conversion of atrial fibrillation into sinus rhythm by laser balloon ablation. AB - The endoscopic laser balloon ablation system affords a unique view of the beating heart for visual guidance in pulmonary vein (PV) isolation. A 66-year-old patient was admitted for catheter ablation of atrial fibrillation (AF). While encircling the left superior PV, AF terminated into sinus rhythm, which was diagnosed by observing sudden regularization of previously rapidly fibrillating atrial tissue demonstrating the unique endoscopic video function. PMID- 22071679 TI - Aneurysmatic disease in patients with Takayasu disease: a case review. AB - Takayasu disease is a non-specific inflammatory disease of the arterial system. Although various etiopathogenetic hypotheses have been formulated, its etiology remains unknown. The aorta and its main branches are predominantly involved in the disease, which is a form of panarteritis, starting with inflammation of the adventitia followed by involvement of the media and intima. It has been more frequently described in young oriental female patients. However, a worldwide distribution is being recognized. Arterial stenosis represents the most frequently diagnosed manifestation. Progression of the flogistic process may lead to stenosis of the aorta and supraaortic vessels, compromising arterial circulation to the brain and upper limbs. Aneurysm presentation may also rarely occur. Based on a recently treated case, the authors report on the clinical presentation, concomitant inflammatory diseases, current diagnostic methods, and management of this disease. PMID- 22071680 TI - Modeling electrical conductivities of nanocomposites with aligned carbon nanotubes. AB - We have developed an improved three-dimensional (3D) percolation model to investigate the effect of the alignment of carbon nanotubes (CNTs) on the electrical conductivity of nanocomposites. In this model, both intrinsic and contact resistances are considered, and a new method of resistor network recognition that employs periodically connective paths is developed. This method leads to a reduction in the size effect of the representative cuboid in our Monte Carlo simulations. With this new technique, we were able to effectively analyze the effects of the CNT alignment upon the electrical conductivity of nanocomposites. Our model predicted that the peak value of the conductivity occurs for partially aligned rather than perfectly aligned CNTs. It has also identified the value of the peak and the corresponding alignment for different volume fractions of CNTs. Our model works well for both multi-wall CNTs (MWCNTs) and single-wall CNTs (SWCNTs), and the numerical results show a quantitative agreement with existing experimental observations. PMID- 22071682 TI - Hypofractionated radiation therapy in the treatment of early-stage breast cancer. AB - Hypofractionated radiation refers to the use of fewer, larger-dose radiation treatments that are usually given over a shorter time period compared to conventional radiation fraction sizes. Randomized trials of hypofractionated whole breast irradiation (WBI) have demonstrated comparable outcomes as conventional fractionation. For a higher-risk population for local recurrence, a phase 3 trial by the Radiation Therapy Oncology Group (RTOG) is currently studying hypofractionated WBI with a concurrent tumor bed boost over 3 weeks. Accelerated partial breast irradiation limits radiation to the region of the tumor bed for 1-3 weeks and is the subject of an ongoing randomized trial by the National Surgical Breast and Bowel Project and RTOG. Questions remain for hypofractionation about optimal patient selection, radiation techniques, and the risk of late toxicity. But results from current trials could make hypofractionation more widely accepted for patients with early-stage breast cancer. PMID- 22071681 TI - Management of brain metastasis: past lessons, modern management, and future considerations. AB - Brain metastasis is a major challenge for patients, physicians, and the broader health care system, with approximately 170,000 new cases per year. After a diagnosis of brain metastasis, patients have a poor prognosis, but modern management has made significant advances in the past two decades to improve palliative efficacy and patient survival through a multidisciplinary approach. A number of factors must be taken into consideration in the treatment approach, including the number of intracranial lesions, the control of extracranial disease, and the patient's overall health, while weighing the benefits of treatment against the toxicities, both acute and chronic. With quality of life as an emphasis, emerging concepts for modern management of brain metastasis have sought to minimize long-term toxicities. The economic impact of such strategies for patients and the health care system has been demonstrated in some studies, but has not been a consistent area of focus. Each of these strategies, as well as novel therapeutics, has embraced the concept of personalized treatment. This review will discuss the current knowledge of modern multidisciplinary management of brain metastasis and look forward to emerging concepts. PMID- 22071683 TI - An intracranial event-related potential study on transformational apparent motion. Does its neural processing differ from real motion? AB - How the brain processes visual stimuli has been extensively studied using scalp surface electrodes and magnetic resonance imaging. Using these and other methods, complex gratings have been shown to activate the ventral visual stream, whereas moving stimuli preferentially activate the dorsal stream. In the current study, a first experiment assessed brain activations evoked by complex gratings using intracranial electroencephalography in 10 epileptic patients implanted with subdural electrodes. These stimuli of intermediate levels of complexity were presented in such a way that transformational apparent motion (TAM) was perceived. Responses from both the ventral and the dorsal pathways were obtained. The response characteristics of visual area 4 and the fusiform cortex were of similar amplitudes, suggesting that both ventral areas are recruited for the processing of complex gratings. On the other hand, TAM-induced responses of dorsal pathway areas were relatively noisier and of lower amplitudes, suggesting that TAM does not activate motion-specific structures to the same extent as does real motion. To test this hypothesis, we examined the activity evoked by TAM in comparison to the one produced by real motion in a patient implanted with the same subdural electrodes. Findings demonstrated that neural response to real motion was much stronger than that evoked by TAM, in both the primary visual cortex (V1) and other motion-sensitive areas within the dorsal pathway. These results support the conclusion that apparent motion, even if perceptually similar to real motion, is not processed in a similar manner. PMID- 22071684 TI - Static prehension of a horizontally oriented object in three dimensions. AB - We studied static prehension of a horizontally oriented object. Specific hypotheses were explored addressing such issues as the sharing patterns of the total moment of force across the digits, presence of mechanically unnecessary digit forces, and trade-off between multi-digit synergies at the two levels of the assumed control hierarchy. Within the assumed hierarchy, at the upper level, the task is shared between the thumb and virtual finger (an imagined finger producing a wrench equal to the sum of the wrenches of individual fingers). At the lower level, action of the virtual finger is shared among the four actual fingers. The subjects held statically a horizontally oriented handle instrumented with six-component force/torque sensors with different loads and torques acting about the long axis of the handle. The thumb acted from above while the four fingers supported the weight of the object. When the external torque was zero, the thumb produced mechanically unnecessary force of about 2.8 N, which did not depend on the external load magnitude. When the external torque was not zero, tangential forces produced over 80% of the total moment of force. The normal forces by the middle and ring fingers produced consistent moments against the external torque, while the normal forces of the index and little fingers did not. Force and moment variables at both hierarchical levels were stabilized by covaried across trials adjustments of forces/moments produced by individual digits with the exception of the normal force analyzed at the lower level of the hierarchy. There was a trade-off between synergy indices computed at the two levels of the hierarchy for the three components of the total force vector, but not for the moment of force components. Overall, the results have shown that task mechanics are only one factor that defines forces produced by individual digits. Other factors, such as loading sensory receptors may lead to mechanically unnecessary forces. There seems to be no single rule (for example, ensuring similar safety margin values) that would describe sharing of the normal and tangential forces and be valid across tasks. Fingers that are traditionally viewed as less accurate (e.g., the ring finger) may perform more consistently in certain tasks. The observations of the trade-off between the synergy indices computed at two levels for the force variables but not for the moment of force variables suggest that the degree of redundancy (the number of excessive elemental variables) at the higher level is an important factor. PMID- 22071686 TI - Nucleation reaction dynamics of Pt nanoparticles observed by the heterodyne transient grating method. AB - The nucleation reaction dynamics of platinum nanoparticles in the photoreduction process of H(2)Pt(IV)Cl(6) solution were investigated by the heterodyne transient grating (HD-TG) method. The formation mechanism of platinum nanoparticles was considered, supported by information obtained from UV/VIS absorption spectroscopy during the reaction and SEM images of the generated nanoparticles. In particular, the roles of poly(N-vinyl-2-pyrrolidone) (PVP) as a protective polymer and ethanol as a solvent were studied. The chemical species involved in the reaction can be identified from the diffusion coefficients obtained from HD-TG measurements; the species observed by UV pulse irradiation were assigned to H(2)Pt(IV)Cl(6) as a reactant species and H(2)Pt(II)Cl(4) and Pt nuclei as product species. It was observed that the amounts of the reactant and product species increased, and many homogeneous nanoparticles were generated, by an increase in PVP concentration. The addition of ethanol to the solvent showed a larger effect on the enhancement of the reduction of H(2)Pt(IV)Cl(6) than that of PVP; however, it did not lead to Pt nuclei formation in the order of seconds. Nevertheless, because nanoparticle formation was confirmed by UV/VIS absorption spectroscopy and SEM images, the formation of nanoparticles following nuclei formation must have proceeded via a slow reaction. Therefore, nucleation and nanoparticle formation are considered to occur on a longer time scale than 10 s in water/ethanol solvent. PMID- 22071685 TI - Suppression of proprioceptive feedback control in movement sequences through intermediate targets. AB - Simple movements can be seen as building blocks for complex action sequences, and neural control of an action sequence can be expected to preserve some control features of its constituent blocks. It was previously found that during single joint elbow movements to a single target, the proprioceptive feedback control is initially suppressed, and we tested this feedback suppression in a two-segment sequence during which subjects momentarily slowed down at an intermediate target at a 30 degrees distance (first segment) and then immediately moved another 30 degrees to the final target (second segment). Either the first or second segment was unexpectedly perturbed; the latency of the earliest response to the perturbation in the muscle surface electromyogram was analyzed. The perturbations were delivered either at the onset of each segment or about 0.1 s later. We found that in both segments, the response latency to the late perturbation was shorter than the latency to the early perturbation, which suggests that the proprioceptive feedback control is suppressed in the beginning of each segment. Next, we determined the latency of the response to unexpected perturbations in 30 degrees movements to a single target. We found that the response latency was not significantly different in the movement to a single target and in each segment in the sequence. This result suggests that the initial suppression of the proprioceptive feedback control in movements to single targets is preserved in movements through intermediate targets and supports the idea of modular organization of neural control of movement sequences. PMID- 22071687 TI - Exhaustive oxidation of a nickel dithiolate complex: some mechanistic insights en route to sulfate formation. AB - A study of the step-wise oxidation of a Ni(II) diaminodithiolate complex through the formation of sulfate, the ultimate sulfur oxygenate, is reported. Controlled oxygenations or peroxidations of a neutral, planar, tetracoordinate, low-spin Ni(II) complex of a N(2)S(2)-donor ligand, (N,N'-dimethyl-N-N'-bis(2 mecaptoethyl)-1,3-propanediaminato) nickel(ii) (1), led to a series of sulfur oxygenates that have been isolated and characterized by ESI-MS and single-crystal X-ray diffraction. A monosulfenate complex (2) was detected by ESI-MS as a product of oxidation with one equivalent of H(2)O(2). However, this complex proved too unstable to isolate. Reaction of the dithiolate (1) with two equivalents of H(2)O(2) or one O(2) molecule leads to the formation of a monosulfinate complex (3), which was isolated and fully characterized by crystallography. The oxidation product of the monosulfinate (3) produced with either O(2) or H(2)O(2) is an interesting dimeric complex containing both sulfonate and thiolate ligands (4), this complex was fully characterized by crystallography, details of which were reported earlier by us. A disulfonate complex (7) is produced by reaction of 1 in the presence of O(2) or by reaction with exactly six equivalents of H(2)O(2). This complex was isolated and also fully characterized by crystallography. Possible intermediates in the conversion of the monosulfinate complex (3) to the disulfonate complex (7) include complexes with mixed sulfonate/sulfenate (5) or sulfonate/sulfinate (6) ligands. Complex 5, a four-oxygen adduct of 1, was not detected, but the sulfonate/sulfinate complex (6) was isolated and characterized. The oxidation chemistry of 1 is very different from that reported for other planar cis-N(2)S(2) Ni(ii) complexes including N,N'-dimethyl-N-N'-bis(2-mecaptoethyl)-1,3-ethylenediaminato) nickel(II), (8), and N,N'-bis(mercaptoethyl)-1,5-diazacyclooctane nickel(II). To address the structural aspects of the reactivity differences, the crystal structure of 8 was also determined. A comparison of the structures of planar Ni(II) complexes containing cis-dithiolate ligands, strongly suggests that the differences in reactivity are determined in part by the degree of flexibility that is allowed by the NN' chelate ring. PMID- 22071688 TI - Assessment of quality of life and depression in spouses of patients with ankylosing spondylitis. AB - The objective of this study is to investigate the quality of life and the rates of depression in spouses/partners of patients with AS compared with spouses/partners of healthy controls". Twenty-five persons with AS and their 25 spouses (21 women and 4 men) and 25 healthy controls were recruited consecutively. All the subjects completed 36-item Short Form Health Survey (SF 36) questionnaire forms and 17-item Hamilton Depression Rating Scale (HAM-D17). Mean age was 35 +/- 6.47 years in spouse group (SG) and 36.26 +/- 5.93 in control group (CG). In SG and CG, the SF-36 subscale scores were compared using Mann Whitney U test. Social functioning, mental health, emotional role, and general health were significantly (P < 0.05) lower in SG compared with CG. The average score of social functioning was found to be 65.41 in spouses of patients compared with healthy controls (90.75). Depression scores were significantly (P < 0.001) higher in SG compared with CG. Among SF-36 subgroups in spouses, general health perception had a negatively significant correlation with depression scores (P < 0.05) and duration of ankylosing spondylitis (P < 0.05). A positively significant correlation has been identified between bodily pain and depression scores in spouses (P < 0.05). Therefore, female partners of male patients were found to be more depressive. Being a spouse of a patient with AS significantly interferes with quality of life and increases the depression frequency. PMID- 22071689 TI - Hysterical paralysis after spinal surgery. AB - This letter is to report and discuss two cases of psychogenic paralysis after spinal surgery in order to increase the vigilance and assist in the diagnosis and treatment of this uncommon disorder. The medical records for two middle-aged men who presented complete loss of extremities function after spinal surgery were reviewed retrospectively. None had a history of a previous hysterical seizure. Both of the patients' symptoms and signs differ from the correct anatomic pattern of a neurological deficit. Both of them spontaneously recovered and discharged from the hospital uneventful eventually. The orthopedic surgeons must recognize hysterical paralysis to avoid unnecessary surgery. A heightened awareness of a nonanatomic functional deficit on physical examination could help to reduce frustration and delay in diagnosis associated with this disorder. Rapid recovery should be expected, but the surgeon should administrate proper treatment. PMID- 22071690 TI - Function of the origin recognition complex 1 (ORC1) outside DNA replication in Drosophila. AB - The origin recognition complex (ORC) is an essential component of the pre replicative complex (pre-RC) that binds to replication origins for licensing. Levels of the largest ORC subunit, ORC1, oscillate during the mitotic cell cycle and regulate origin usage. In Drosophila, ORC1 levels increase at the G(1)/S transition following E2F-dependent transcriptional activation, remain high until the end of M phase and then decrease at the M/G(1) transition when ORC1 is targeted for proteolysis by the anaphase-promoting complex (APC). A function, if any, for Drosophila ORC1 after S phase has not been described. Here, we determined the role of ORC1 at stages outside S phase by generating ORC1 derivatives with a modified ORC1 degradation box (the O-box) and examining the effects in vivo. These modifications either stabilized ORC1 by mutating the O-box (ORC1(Omut)) so that it is no longer targeted by APC or changed its degradation profile by replacing the O-box with the D-box of human cyclin B (ORC1(O->D)), so that degradation would occur earlier. We determined the distribution and tested the function of these ORC1 derivatives in an orc1 mutant background so that only the mutated protein was expressed. Stable version of ORC1, ORC1 (Omut), showed no effects on cell cycle progression; however, ORC1(O->D), which is degraded early at the G(2)/M transition, led to a higher frequency of M-phase cells but not S phase cells. Taken together, our results indicate the timing of ORC1 degradation is required for timely progression in M phase. PMID- 22071692 TI - Phosphorylation of von Hippel-Lindau protein by checkpoint kinase 2 regulates p53 transactivation. AB - von-Hippel Lindau protein (pVHL) suppresses tumorigenesis in the kidney, in part through regulation of hypoxia-inducible factor alpha (HIF alpha). However, HIF has been proposed to be necessary but insufficient for renal tumorigenesis. p53 was implicated as a transcription factor that is regulated by pVHL, but the molecular mechanism by which pVHL regulates p53 on DNA damage is unknown. We demonstrated that checkpoint kinase-2 (Chk2) binds to the beta-domain of pVHL and phosphorylates Ser 111 on DNA damage. Notably, this modification enhances pVHL mediated transactivation of p53 by recruiting p300 and Tip60 to the chromatin of p53 target gene. Further, the naturally occurring pVHL mutants pVHL-S111R and pVHL-S111C showed diminished binding to coactivators, ultimately retarding p53 mediated growth arrest and apoptosis. In this study, we determined the molecular mechanism by which pVHL transactivates p53 on DNA damage and demonstrated that p53-related pVHL subtype mutants regulate tumorigenecity in VHL diseases. PMID- 22071693 TI - Nuclear import of a lipid-modified transcription factor: mobilization of NFAT5 isoform a by osmotic stress. AB - Lipid-modified transcription factors (TFs) are biomolecular oddities since their reduced mobility and membrane attachment appear to contradict nuclear import required for their gene-regulatory function. NFAT5 isoform a (selected from an in silico screen for predicted lipid-modified TFs) is shown to contribute about half of all endogenous expression of human NFAT5 isoforms in the isotonic state. Wild type NFAT5a protein is indeed myristoylated and palmitoylated on its transport to the plasmalemma via the endoplasmic reticulum and the Golgi. In contrast, its lipid anchor-deficient mutants as well as isoforms NFAT5b/c are diffusely localized in the cytoplasm without preference to vesicular structures. Quantitative/live microscopy shows the plasmamembrane-bound fraction of NFAT5a moving into the nucleus upon osmotic stress despite the lipid anchoring. The mobilization mechanism is not based on proteolytic processing of the lipid anchored N-terminus but appears to involve reversible palmitoylation. Thus, NFAT5a is an example of TFs immobilized with lipid anchors at cyotoplasmic membranes in the resting state and that, nevertheless, can translocate into the nucleus upon signal induction. PMID- 22071694 TI - Cyclin B1 interacts with the BH3-only protein Bim and mediates its phosphorylation by Cdk1 during mitosis. AB - Protracted mitotic arrest leads to cell death; however, the molecular signals that link these distinct processes remain poorly understood. Here we report that the pro-apoptotic BH3-only family member Bim undergoes phosphorylation in K562 cells following treatment with the microtubule targeting agents Taxol and Nocodazole. The phosphorylation of two Bim isoforms, BimEL and BimL, at the mitochondria correlates with mitotic arrest and precedes cell death induced by Taxol. It was also found that Bim undergoes transient phosphorylation during normal mitosis in K562 cells. In addition, siRNA silencing of Bim reduces sensitivity to Taxol-induced cell death. The transition of K562 cells from mitosis to G1 results in the loss of BimEL and BimL phosphorylation and correlates with the degradation of cyclin B1. The Cdk1 inhibitors, RO-3306 and Purvalanol A, block Bim phosphorylation in mitotically arrested cells. Importantly, it was found that cyclin B1 co-immunoprecipitates with endogenous Bim in mitotic extracts. Furthermore, active recombinant Cdk1/cyclin B1 phosphorylates BimEL and BimL in vitro and Serine 44 on BimL has been identified as a Cdk1 phosphorylation site. Collectively, these results suggest that Cdk1/cyclin B1-dependent hyper-phosphorylation of Bim during prolonged mitotic arrest is an important cell death signal. PMID- 22071691 TI - Phospho-DeltaNp63alpha/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure. AB - The cisplatin-induced ATM-dependent phosphorylated (p)-DeltaNp63alpha plays an important role in transcriptional regulation of specific genes encoding mRNAs and microRNAs (miRs) implicated in cell death, cell survival, and chemoresistance. The p-DeltaNp63alpha-induced miR-885-3p functions as a critical regulator of MDM4, ATK1, BCL2, ATG16L2, ULK2, CASP2, and CASP3 mRNAs via pairing with their respective 'recognition' sequences. Cisplatin exposure modulated the levels of target proteins (reduced BCL2, AKT1, ATG16L2, and ULK2, while activated MDM4) in cisplatin-sensitive wild type DeltaNp63alpha cells leading to distinct changes in cell viability. Finally, miR-885-3p modulated the cisplatin-induced TP53 dependent mitochondrial apoptosis by up regulation of MDM4 levels and down regulation of BCL2 levels in mitochondria. Altogether, our results support the notion that miR-885-3p might contribute in regulation of cell viability, apoptosis and/or autophagy in squamous cell carcinoma cells upon cisplatin exposure. PMID- 22071695 TI - Mitotic chromosome size scaling in Xenopus. AB - As rapid divisions without growth generate progressively smaller cells within an embryo, mitotic chromosomes must also decrease in size to permit their proper segregation, but this scaling phenomenon is poorly understood. We demonstrated previously that nuclear and spindle size scale between egg extracts of the related frog species Xenopus tropicalis and Xenopus laevis, but show here that dimensions of isolated mitotic sperm chromosomes do not differ. This is consistent with the hypothesis that chromosome scaling does not occur in early embryonic development when cell and spindles sizes are large and anaphase B segregates chromosomes long distances. To recapitulate chromosome scaling during development, we combined nuclei isolated from different stage Xenopus laevis embryos with metaphase-arrested egg extracts. Mitotic chromosomes derived from nuclei of cleaving embryos through the blastula stage were similar in size to replicated sperm chromosomes, but decreased in area approximately 50% by the neurula stage, reproducing the trend in size changes observed in fixed embryos. Allowing G2 nuclei to swell in interphase prior to mitotic condensation did not increase mitotic chromosome size, but progression through a full cell cycle in egg extract did, suggesting that epigenetic mechanisms determining chromosome size can be altered during DNA replication. Comparison of different sized mitotic chromosomes assembled in vitro provides a tractable system to elucidate underlying molecular mechanisms. PMID- 22071696 TI - Pharmacology of the new treatments for lower gastrointestinal motility disorders and irritable bowel syndrome. PMID- 22071697 TI - NANOG priming before full reprogramming may generate germ cell tumours. AB - Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC) lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation. PMID- 22071698 TI - Transplantatation of scaffold-free spheroids composed of synovium-derived cells and chondrocytes for the treatment of cartilage defects of the knee. AB - Autologous chondrocyte implantation (ACI) is the treatment of choice for osteoarthritis. However, to regenerate articular cartilage using this method, the procedure paradoxically demands that the cell source of the articular chondrocytes (ACs) for ex vivo expansion be from the patient's own healthy cartilage, which can result in donor site morbidity. Accordingly, it is essential to develop a substitute for AC. In the present study, we investigated whether synovium-derived cells (SYs) could be used as a partial replacement for ACs in ACI. ACs and SYs from the knees of rabbits were isolated and cultured, and the growth rates of the cells were compared. To manufacture the cellular transplants, we developed a high-density suspension-shaking culture method (HDSS), which circulates the cells in culture media, promoting self-assembly of scaffold-free cellular aggregates. ACs and SYs were mixed in various ratios using HDSS. Injectable cellular transplants were harvested and transplanted into full thickness osteochondral defects. Simultaneously, histological evaluations were conducted with toluidine blue and safranin O, and immunohistochemistry of collagen type I and II was conducted. Gene expression to evaluate chondrocyte specific differentiation was also performed. We successfully prepared a large quantity of spheroids (spheroidal cell aggregates) in a short time using mixed ACs and SYs, for all cellular composition ratios. Our data showed that the minimal therapeutic unit for the transplants contributed to in situ regeneration of cartilage. In summary, SYs can be used as a replacement for ACs in clinical cases of ACI in patients with broad areas of osteoarthritic lesions. PMID- 22071699 TI - Continuous glucose monitoring to assess the ecologic validity of dietary glycemic index and glycemic load. AB - BACKGROUND: The circumstances under which the glycemic index (GI) and glycemic load (GL) are derived do not reflect real-world eating behavior. Thus, the ecologic validity of these constructs is incompletely known. OBJECTIVE: This study examined the relation of dietary intake to glycemic response when foods are consumed under free-living conditions. DESIGN: Participants were 26 overweight or obese adults with type 2 diabetes who participated in a randomized trial of lifestyle modification. The current study includes baseline data, before initiation of the intervention. Participants wore a continuous glucose monitor and simultaneously kept a food diary for 3 d. The dietary variables included GI, GL, and intakes of energy, fat, protein, carbohydrate, sugars, and fiber. The glycemic response variables included AUC, mean and SD of continuous glucose monitoring (CGM) values, percentage of CGM values in euglycemic and hyperglycemic ranges, and mean amplitude of glycemic excursions. Relations between daily dietary intake and glycemic outcomes were examined. RESULTS: Data were available from 41 d of monitoring. Partial correlations, controlled for energy intake, indicated that GI or GL was significantly associated with each glycemic response outcome. In multivariate analyses, dietary GI accounted for 10% to 18% of the variance in each glycemic variable, independent of energy and carbohydrate intakes (P < 0.01). CONCLUSIONS: The data support the ecologic validity of the GI and GL constructs in free-living obese adults with type 2 diabetes. GI was the strongest and most consistent independent predictor of glycemic stability and variability. PMID- 22071700 TI - Palm oil and LDL cholesterol. PMID- 22071701 TI - Effects of iron supplementation on serum hepcidin and serum erythropoietin in low birth-weight infants. AB - BACKGROUND: The iron-regulatory hormone hepcidin has not been studied in infants, who experience large physiologic changes in iron status. OBJECTIVE: The objective was to study hepcidin and erythropoietin and their correlation with iron status in iron-replete and iron-deficient low-birth-weight (LBW) infants-a group at particular risk of iron deficiency (ID). DESIGN: We randomly assigned 285 otherwise healthy LBW infants to receive, from 6 wk to 6 mo of age, 3 doses of iron supplements: 0 (placebo), 1, or 2 mg/kg daily. Hepcidin, erythropoietin, hemoglobin, and variables of iron status were analyzed. RESULTS: Serum hepcidin did not change over time in the placebo group, despite a rapid decrease in serum ferritin. In iron-supplemented infants, hepcidin increased significantly, reaching a mean (+/-SD) concentration of 19.2 +/- 2.5 ng/mL in the 2-mg/kg group compared with 13.0 +/- 2.6 ng/mL in the placebo group at age 6 mo (P < 0.001). The difference was even larger between iron-deficient and iron-replete infants. Hepcidin was independently positively correlated with ferritin at all ages and was negatively correlated with the transferrin receptor concentration at age 6 wk and with transferrin at age 6 mo. Erythropoietin was initially similar between groups but decreased significantly in iron-supplemented infants. In addition to being negatively correlated with hemoglobin, it was also independently negatively correlated with indicators of iron status. CONCLUSIONS: Hepcidin is closely associated with iron status and may be a useful indicator of iron stores and ID in infants. Erythropoietin is negatively correlated with iron status, which suggests a feedback mechanism that needs further study. This trial is registered at clinicaltrials.gov as NCT00558454. PMID- 22071702 TI - Prospective associations between appetitive traits and weight gain in infancy. AB - BACKGROUND: Differences in appetitive traits such as food-cue or satiety responsiveness have been hypothesized to contribute to variability in weight gain. However, existing data were largely cross-sectional and could not exclude the possibility that differences in appetitive traits were consequences of differences in weight. OBJECTIVE: We tested whether prospective associations between appetitive traits and subsequent weight were stronger than associations between weight and subsequent appetitive traits. DESIGN: Data were from Gemini, which is a population-based cohort of 2402 families with twins. Parents completed a Baby Eating Behavior Questionnaire to assess 4 appetitive traits for each twin at ages 3 and 15 mo. We obtained infant weights at 3, 9, and 15 mo from records of health professionals. Weight SD scores were calculated by using UK 1990 reference data. A path analysis was used to examine prospective associations in each direction over sequential 6-mo intervals and over the same 12-mo period, with the significance of differences between the 2 paths established with bootstrapping. RESULTS: Path analyses included 2213 infants. For each appetitive trait, the path to subsequent weight (standardized coefficients: 0.17-0.33) was significantly larger than the path from weight to subsequent appetite (coefficients: 0.07-0.13). Results were confirmed when both associations were analyzed by using changes from 3 to 15 mo. CONCLUSION: Longitudinal analyses showed that associations between appetitive traits and subsequent weight were stronger than between weight and subsequent appetite, which supports the idea that differences in appetitive traits, in conjunction with environmental opportunities to overeat, influence weight gain in early childhood. PMID- 22071703 TI - Nutrient requirements to optimize neonatal growth. PMID- 22071704 TI - Mediterranean-style diet and risk of ischemic stroke, myocardial infarction, and vascular death: the Northern Manhattan Study. AB - BACKGROUND: A dietary pattern common in regions near the Mediterranean appears to reduce risk of all-cause mortality and ischemic heart disease. Data on blacks and Hispanics in the United States are lacking, and to our knowledge only one study has examined a Mediterranean-style diet (MeDi) in relation to stroke. OBJECTIVE: In this study, we examined an MeDi in relation to vascular events. DESIGN: The Northern Manhattan Study is a population-based cohort to determine stroke incidence and risk factors (mean +/- SD age of participants: 69 +/- 10 y; 64% women; 55% Hispanic, 21% white, and 24% black). Diet was assessed at baseline by using a food-frequency questionnaire in 2568 participants. A higher score on a 0 9 scale represented increased adherence to an MeDi. The relation between the MeDi score and risk of ischemic stroke, myocardial infarction (MI), and vascular death was assessed with Cox models, with control for sociodemographic and vascular risk factors. RESULTS: The MeDi-score distribution was as follows: 0-2 (14%), 3 (17%), 4 (22%), 5 (22%), and 6-9 (25%). Over a mean follow-up of 9 y, 518 vascular events accrued (171 ischemic strokes, 133 MIs, and 314 vascular deaths). The MeDi score was inversely associated with risk of the composite outcome of ischemic stroke, MI, or vascular death (P-trend = 0.04) and with vascular death specifically (P-trend = 0.02). Moderate and high MeDi scores were marginally associated with decreased risk of MI. There was no association with ischemic stroke. CONCLUSIONS: Higher consumption of an MeDi was associated with decreased risk of vascular events. Results support the role of a diet rich in fruit, vegetables, whole grains, fish, and olive oil in the promotion of ideal cardiovascular health. PMID- 22071705 TI - Intake of fruit, vegetables, and carotenoids in relation to risk of uterine leiomyomata. AB - BACKGROUND: US black women have higher rates of uterine leiomyomata (UL) and lower intakes of fruit and vegetables than do white women. Whether fruit and vegetable intake is associated with UL in black women has not been studied. OBJECTIVE: We assessed the association of dietary intake of fruit, vegetables, carotenoids, folate, fiber, and vitamins A, C, and E with UL in the Black Women's Health Study. DESIGN: In this prospective cohort study, we followed 22,583 premenopausal women for incident UL (1997-2009). Diet was estimated by using food frequency questionnaires in 1995 and 2001. Cox regression was used to derive incidence rate ratios (IRRs) and 95% CIs for the association between each dietary variable (in quintiles) and UL. RESULTS: There were 6627 incident cases of UL diagnosed by ultrasonography (n = 4346) or surgery (n = 2281). Fruit and vegetable intake was inversely associated with UL (>=4 compared with <1 serving/d; IRR: 0.90; 95% CI: 0.82, 0.98; P-trend = 0.03). The association was stronger for fruit (>=2 servings/d compared with <2 servings/wk; IRR: 0.89; 95% CI: 0.81, 0.98; P-trend = 0.07) than for vegetables (>=2 servings/d compared with <4 servings/wk: IRR: 0.97; 95% CI: 0.89, 1.05; P-trend = 0.51). Citrus fruit intake was inversely associated with UL (>=3 servings/wk compared with <1 serving/mo: IRR: 0.92; 95% CI: 0.86, 1.00; P-trend = 0.01). The inverse association for dietary vitamin A (upper compared with lower quintiles: IRR: 0.89; 95% CI: 0.83, 0.97; P-trend = 0.01) appeared to be driven by preformed vitamin A (animal sources), not provitamin A (fruit and vegetable sources). UL was not materially associated with dietary intake of vitamins C and E, folate, fiber, or any of the carotenoids, including lycopene. CONCLUSION: These data suggest a reduced risk of UL among women with a greater dietary intake of fruit and preformed vitamin A. PMID- 22071706 TI - The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. AB - BACKGROUND: Choline is the precursor to the neurotransmitter acetylcholine. Loss of cholinergic neurons is associated with impaired cognitive function, particularly memory loss and Alzheimer disease (AD). Brain atrophy and white matter hyperintensity (WMH) are also associated with impaired cognitive function and AD. OBJECTIVE: The objective was to determine whether a relation exists between dietary choline intake, cognitive function, and brain morphology in a large, nondemented community-based cohort. DESIGN: A dementia-free cohort of 1391 subjects (744 women, 647 men; age range: 36-83 y; mean +/- SD age: 60.9 +/- 9.29 y) from the Framingham Offspring population completed a food-frequency questionnaire administered from 1991 to 1995 (exam 5; remote intake) and from 1998 to 2001 (exam 7; concurrent intake). Participants underwent neuropsychological evaluation and brain MRI at exam 7. Four neuropsychological factors were constructed: verbal memory (VM), visual memory (VsM), verbal learning, and executive function. MRI measures included WMH volume (WMHV). RESULTS: Performance on the VM and VsM factors was better with higher concurrent choline intake in multivariable-adjusted models for VM (average change in neuropsychological factor per 1-unit change in choline = 0.60; 95% CI: 0.29, 0.91; P < 0.01) and VsM (0.66; 95% CI: 0.19, 1.13; P < 0.01). Remote choline intake was inversely related to log-transformed WMHV (average change in log WMHV per 1-unit change in choline = -0.05; 95% CI: -0.10, -0.01; P = 0.02). Furthermore, an inverse association was observed between remote higher choline intake and presence of large WMVH (OR: 0.56; 95% CI: 0.34, 0.92; P = 0.01). CONCLUSION: In this community-based population of nondemented individuals, higher concurrent choline intake was related to better cognitive performance, whereas higher remote choline intake was associated with little to no WMHV. PMID- 22071707 TI - Biomarker-calibrated dietary energy and protein intake associations with diabetes risk among postmenopausal women from the Women's Health Initiative. AB - BACKGROUND: Self-report of dietary energy and protein intakes has been shown to be systematically and differentially underreported. OBJECTIVE: We assessed and compared the association of diabetes among postmenopausal women with biomarker calibrated and uncalibrated dietary energy and protein intakes from food frequency questionnaires (FFQs). DESIGN: The analyses were performed for 74,155 participants of various race-ethnicities from the Women's Health Initiative. Uncalibrated and calibrated energy and protein intakes from FFQs were assessed for associations with incident diabetes by using HR estimates based on Cox regression. RESULTS: A 20% increment in uncalibrated energy consumption was associated with increased diabetes risk (HR) of 1.03 (95% CI: 1.01, 1.05), 2.41 (95% CI: 2.06, 2.82) with biomarker calibration, and 1.30 (95% CI: 0.96, 1.76) after adjustment for BMI. A 20% increment in uncalibrated protein (g/d) resulted in an HR of 1.05 (95% CI: 1.03, 1.07), 1.82 (95% CI: 1.56, 2.12) with calibration, and 1.16 (95% CI: 1.05, 1.28) with adjustment for BMI. A 20% increment in uncalibrated protein density (% of energy from protein) resulted in an HR of 1.13 (95% CI: 1.09, 1.17), 1.01 (95% CI: 0.75, 1.37) with calibration, and 1.19 (95% CI: 1.07, 1.32) with adjustment for BMI. CONCLUSIONS: Higher protein and total energy intakes (calibrated) appear to be associated with a substantially increased diabetes risk that may be mediated by an increase in body mass over time. Diet-disease associations without correction of self-reported measurement error should be viewed with caution. This trial is registered at clinicaltrials.gov as NCT00000611. PMID- 22071708 TI - Effect of fatty acid status in cord blood serum on children's behavioral difficulties at 10 y of age: results from the LISAplus Study. AB - BACKGROUND: Little is known about the effect of fatty acid (FA) concentrations in cord blood on long-term behavioral outcomes. OBJECTIVE: We assessed the effect of FAs in cord blood serum on children's behavioral difficulties at the age of 10 y. DESIGN: A longitudinal study of 416 children from the population-based Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood (LISAplus) birth cohort from Munich was conducted. Individual glycerophospholipid FAs in blood were analyzed in venous cord blood. Data on children's behavior were collected with a parent-reported Strength and Difficulties Questionnaire at 10 y of age. Zero-inflated Poisson regression models were applied and adjusted for sex, parental income, smoking during pregnancy, and dietary intake of arachidonic acid (AA) and DHA at 10 y. RESULTS: A 1% increase in DHA in cord blood serum was found to decrease total difficulties by (exp)beta(adj) = 0.93 (SE = 0.02, P < 0.0001) and hyperactivity or inattention by (exp)beta(adj) = 0.94 (SE = 0.03, P < 0.04). Higher long-chain (LC) PUFA concentrations in cord blood serum were associated with fewer emotional symptoms [(exp)beta(adj) = 0.95, SE = 0.03, P = 0.01], and similarly higher AA concentrations were associated with fewer emotional symptoms [(exp)beta(adj) = 0.94, SE = 0.03, P = 0.03]. CONCLUSION: Increased concentrations of DHA, LC PUFAs, and AA in cord blood serum were associated with lower scores on a parent completed behavioral screen. An appropriate FA supply to the developing fetus may be essential for optimal long-term behavioral outcomes in children. PMID- 22071709 TI - The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males. AB - BACKGROUND: Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents. OBJECTIVE: We sought to investigate the effect of acutely elevating leptin to concentrations observed in obese individuals on muscle and adipose tissue metabolism and muscle signaling in healthy lean males. DESIGN: Healthy, lean, postabsorptive males were infused with either recombinant human leptin (rhleptin; n = 8) or saline (control; n = 8) for 4 h, which elicited leptin concentrations of ~ 20 and ~ 1 ng/mL, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism in vivo were assessed before, during, and 2 h after cessation of the infusion. Skeletal muscle biopsy specimens were obtained to quantify changes in signal transducers and activators of transcription-5'AMP-activated protein kinase (STAT-AMPK) signaling. RESULTS: During the infusion of rhleptin, no differences in either systemic, skeletal muscle, or adipose tissue glucose or fat metabolism were observed. These observations were made despite increased activation of STAT (~ 17-fold) and AMPK (1.43-fold) after 1 h of rhleptin infusion. After the rhleptin infusion, an increase in systemic palmitate and fat oxidation was observed (P < 0.0003), which likely was caused by a concomitant increase in skeletal muscle palmitate oxidation (P < 0.02). This was observed despite lowered leptin concentrations and basal skeletal muscle STAT-AMPK signaling. CONCLUSIONS: Elevating circulating leptin concentrations to concentrations comparable with those of obese individuals increases human in vivo skeletal muscle signaling through the AMPK pathway and causes an increase in skeletal muscle fatty acid oxidation. Abdominal adipose tissue was unaffected by the acute physiologic increase in leptin concentrations. PMID- 22071710 TI - Maternal vitamin A and beta-carotene supplementation and risk of bacterial vaginosis: a randomized controlled trial in rural Bangladesh. AB - BACKGROUND: Bacterial vaginosis (BV) in pregnancy is linked to preterm birth, but its risk factors are not well understood. Micronutrient deficiencies may be associated with an increased risk of this condition. OBJECTIVE: We assessed the effect of weekly vitamin A or beta-carotene supplementation during pregnancy until 3 mo postpartum on BV risk in rural northeastern Bangladesh. DESIGN: In this cluster-randomized, placebo-controlled trial, 33 clusters (n = 33) were randomly assigned to 3 groups. Women (n = 1812) were examined for BV by using self-administered swabs and the Nugent scoring method in early pregnancy, at 32 wk of gestation, and at 3 mo postpartum. RESULTS: The prevalence of BV in early pregnancy, before supplementation, was 7.6% (95% CI: 6.3%, 9.1%) overall. Neither the prevalence nor the incidence of BV in the third trimester differed by supplement group. However, the prevalence (OR: 0.71; 95% CI: 0.52, 0.98) and incidence (RR: 0.58; 95% CI: 0.41, 0.81) of BV at 3 mo postpartum was lower among women in the vitamin A group (9.1% and 6.7%, respectively) than in the placebo group (12.4% and 11.8%, respectively), but not in the beta-carotene group. Both vitamin A and beta-carotene reduced the prevalence and incidence of BV at both time points (ie, third trimester and 3 mo postpartum) by 30-40% compared with placebo (all P < 0.05). CONCLUSIONS: Weekly vitamin A supplementation reduced the risk of maternal BV in this rural Bangladeshi population. Enhancement of vitamin A status before and during pregnancy may reduce the risk of BV in areas with vitamin A deficiency. This trial is registered at clinicaltrials.gov as NCT00198822. PMID- 22071711 TI - Palm olein increases plasma cholesterol moderately compared with olive oil in healthy individuals. AB - BACKGROUND: Despite the high content of palmitic acid, palm olein has been shown to have a neutral effect on plasma cholesterol concentrations when compared with olive oil, which is suggested to be attributable to palmitic acid in the sn-1 and sn-3 position. In contrast, palmitic acid is in the sn-2 position in lard. OBJECTIVE: The objective was to investigate the effects of a diet rich in palm olein, fractionated palm oil, olive oil, and lard on plasma blood lipids, inflammatory markers, glucose, and insulin. DESIGN: A controlled double-blinded, randomized 3 * 3 wk crossover dietary intervention study included 32 healthy men who daily replaced part of their habitual dietary fat intake with ~ 17% of energy from palm olein, olive oil, or lard, respectively. RESULTS: Compared with intake of olive oil, palm olein and lard increased total cholesterol and LDL cholesterol (P < 0.0001). Palm olein resulted in a lower plasma triacylglycerol concentration than did olive oil (P < 0.01). No difference in effects was observed in plasma HDL-cholesterol, high-sensitivity C-reactive protein, plasminogen activator-1, insulin, and glucose concentrations. CONCLUSIONS: The current study did not support the previous finding that the effect of palm olein on total plasma cholesterol and LDL cholesterol in healthy individuals with normal plasma cholesterol concentrations is neutral compared with that of olive oil. Thus, sn positioning was not confirmed to be important with regard to the effect on plasma cholesterol. The relatively lower plasma triacylglycerol concentration after the palm olein diet than after the olive oil diet was unexpected. This trial is registered at clinicaltrials.gov as NCT00743301. PMID- 22071712 TI - Soy intake is associated with lower lung cancer risk: results from a meta analysis of epidemiologic studies. AB - BACKGROUND: Although several in vitro and animal in vivo studies have suggested that soy or soy isoflavones may exert inhibitory effects on lung carcinogenesis, epidemiologic studies have reported inconclusive results on the association between soy intake and lung cancer. OBJECTIVE: The aim of this meta-analysis was to investigate whether an association exists between soy and lung cancer in epidemiologic studies. DESIGN: We searched PubMed, EMBASE, and the Cochrane Library from their inception to February 2011 for both case-control and cohort studies that assessed soy consumption and lung cancer risk. Study-specific risk estimates were combined by using fixed-effect or random-effect models. RESULTS: A total of 11 epidemiologic studies that consisted of 8 case-control and 3 prospective cohort studies were included. A significantly inverse association was shown between soy intake and lung cancer with an overall RR of 0.77 (95% CI: 0.65, 0.92). Findings were slightly different when analyses were restricted to 5 high-quality studies (RR: 0.70; 95% CI: 0.45, 0.99). In a subgroup meta-analysis, a statistically significant protective effect of soy consumption was observed in women (RR: 0.79; 95% CI: 0.67, 0.93), never smokers (RR: 0.62; 95% CI: 0.51, 0.76), and Asian populations (RR: 0.86; 95% CI: 0.74, 0.98). CONCLUSIONS: Our findings indicate that the consumption of soy food is associated with lower lung cancer risk. Because of different methods used to assess soy consumption across studies, more well-designed cohort studies or intervention studies that use unified measures of soy intake are needed to fully characterize such an association. PMID- 22071713 TI - Changes in genetic and environmental effects on growth during infancy. AB - BACKGROUND: Accelerated infant growth is a possible explanation for the relation between birth weight and adult diseases. OBJECTIVE: The aim of this study was to estimate the heritability of infant growth and to examine whether the genetic contribution changes with increasing or decreasing birth weight and gestational age. DESIGN: Growth (change in weight z score) was analyzed in 522 infants from the East Flanders Prospective Twin Survey for age windows of 0-1, 1-6, 6-12, and 12-24 mo. Structural equation modeling was performed to estimate the relative importance of additive genetic, shared environmental, and unique environmental sources of variance. RESULTS: We showed no genetic contribution to growth in the 0-1-mo growth period. However, at later ages, the heritability of growth was high at 94% (95% CI: 90%, 96%) from 1 to 6 mo, 85% (95% CI: 80%, 89%) from 6 to 12 mo, and 86% (95% CI: 77%, 91%) in the 12-24-mo growth period. Nevertheless, in the last age window, a model without genetic factors was also statistically plausible. From 0 to 1 mo, the genetic contribution to growth was low in the average birth weight range but higher at both extremes of birth weight. The genetic contribution from 0 to 1 mo increased with increasing gestational age from 36 wk of gestation onward. CONCLUSIONS: This study shows that genetic factors are not important in early infant growth (0-1 mo), whereas heritability is high after 1 mo. Because many (nutritional) interventions are aimed at influencing early postnatal growth, to target long-term health, these interventions may be most successful if implemented in the first month of postnatal growth. PMID- 22071714 TI - Low-grade adipose tissue inflammation in patients with mild-to-moderate chronic obstructive pulmonary disease. AB - BACKGROUND: Low-grade systemic inflammation is common in chronic obstructive pulmonary disease (COPD), but its source remains unclear. Adipose tissue is a potent producer of inflammatory mediators and may contribute to systemic inflammation in COPD, possibly via hypoxia. OBJECTIVE: We studied the influence of COPD and exercise-induced oxygen desaturation on adipose tissue inflammation (ATI) and its contribution to systemic inflammation. DESIGN: Subcutaneous adipose tissue biopsies were investigated in 28 clinically stable COPD patients [forced expiratory volume in 1 s: 58 +/- 16% predicted; BMI (in kg/m(2)): 24.9 +/- 2.9] and 15 age-, sex-, and body composition-matched healthy control subjects. Fat mass was measured with dual-energy X-ray absorptiometry. Patients were prestratified by oxygen desaturation assessed by incremental cycle ergometry. The adipocyte size and adipose tissue expression of 19 inflammatory and hypoxia related genes were measured, and adipose tissue macrophages (ATMs) were histologically quantified. Systemic inflammatory markers included C-reactive protein (CRP) and a panel of 20 adipokines. RESULTS: COPD patients had comparable fat mass but higher CRP and HOMA-IR than did control subjects. COPD patients and control subjects had comparable adipose tissue gene expression, adipocyte size, ATM infiltration, and systemic adipokine concentrations. Desaturating COPD patients had no different ATI status than did nondesaturating COPD patients. COPD patients with high CRP had significantly greater ATM infiltration than did patients with low CRP, which was independent of BMI and fat mass. CONCLUSIONS: In COPD patients, mild-to-moderate COPD, per se, does not enhance ATI or its contribution to systemic inflammation compared with in well-matched healthy control subjects. However, to our knowledge, our study provides a first indication for a possible role of ATMs in the systemic inflammatory response in COPD that requires additional investigation. This trial was registered at www.trialregister.nl as NTR1402. PMID- 22071715 TI - Adolescent and mid-life diet: risk of colorectal cancer in the NIH-AARP Diet and Health Study. AB - BACKGROUND: Colorectal cancer has a natural history of several decades; therefore, the diet consumed decades before diagnosis may aid in understanding this malignancy. OBJECTIVE: The objective was to investigate diet during adolescence and 10 y before baseline (ages 40-61 y) in relation to colorectal cancer. DESIGN: Participants in the NIH-AARP Diet and Health Study (n = 292,797) completed a 124-item food-frequency questionnaire (FFQ) about diet in the past 12 mo and two 37-item FFQs about diet at ages 12-13 y and 10 y previously. Cox regression was used to estimate multivariate HRs and 95% CIs for colon (n = 2794) and rectal (n = 979) cancers within quintiles of exposures. RESULTS: Colon cancer risk was lower in the highest than in the lowest quintile of vitamin A (HR: 0.82; 95% CI: 0.72, 0.92) and vegetable (HR: 0.81, 0.70, 0.92) intakes during adolescence. Those in the highest intake category 10 y previously for calcium (HR: 0.83; 95% CI: 0.73, 0.94), vitamin A (HR: 0.81; 95% CI: 0.71, 0.92), vitamin C (HR: 0.83; 95% CI: 0.72, 0.95), fruit (HR: 0.84; 95% CI: 0.73, 0.97), and milk (HR: 0.78; 95% CI: 0.67, 0.90) had a lower risk of colon cancer, but a higher risk was observed for total fat (HR: 1.15; 95% CI: 1.01, 1.30), red meat (HR: 1.31; 95% CI: 1.12, 1.53), and processed meat (HR: 1.24; 95% CI: 1.06, 1.45). For rectal cancer, milk was inversely associated (HR: 0.75; 95% CI: 0.58, 0.96) with risk. CONCLUSION: Adolescent and midlife diet may play a role in colorectal carcinogenesis. PMID- 22071716 TI - Surgical repair of scrolled descemet's membrane detachment with intracameral injection of 1.8% sodium hyaluronate. AB - We report the case of a 76-year-old woman with scrolled Descemet's membrane detachment (DMD) that was successfully treated by an intracameral injection of 1.8% sodium hyaluronate. During phacoemulsification cataract surgery, an undulating DMD involving the central cornea was observed and air tamponade into the anterior chamber was performed. The patient underwent surgical repair 2 weeks after the unsuccessful intracameral air injection. To increase the tamponade pressure and surface tension on the scrolled flap, viscoelastic material was injected into the air-filled anterior chamber. Corneal edema started subsiding clinically after the injection of sodium hyaluronate. Descemetopexy with sodium hyaluronate can successfully repair scrolled DMD and injection of viscoelastic material into the air-filled anterior chamber facilitates unfolding of the scrolled flap of DMD. PMID- 22071717 TI - Improving sexual risk communication with adolescents using event history calendars. AB - This study was conducted to explore the effects of an event history calendar (EHC) approach on adolescent sexual risk communication and sexual activity. Adolescent school-linked health clinic patients (n = 30) who reported sexual activity self-administered the EHC that was used by nurse practitioners (NPs; n = 2) during a clinic visit. Immediately pre- and post-visit, and at 1 and 3 months, adolescents reported sexual risk behaviors and perceptions about EHC communication on questionnaires and by interview. NPs reported their perceptions of EHCs by questionnaire after the visit and poststudy interview. The EHC approach facilitated communication and adolescent awareness of their risk behaviors. Scores increased on Amount of Communication, t(29) = 8.174, p < .001; Satisfaction with Communication, t(29) = 3.112, p = .004; Client Involvement in Decision Making, t(29) = 3.901, p = .001, and Client Satisfaction with Interpersonal Style, t(29) = 3.763, p = .001. Adolescents reported decreased sexual intercourse at 1 month, p = .031. School nurses could use the EHC approach to facilitate adolescent communication and tailoring of interventions. PMID- 22071718 TI - Effect of surface pressurization on the growth of alpha-Fe2O3 nanostructures. AB - By suitably pressurizing iron substrates under different conditions, the resulting alpha-Fe(2)O(3) nanostructures, formed by its direct thermal oxidation, can gradually change in succession from nanowires to nanoleaves and to micropillars as the pressure is increased. The inter-relation between the pressure conditions and the resulting nanostructure is studied by density functional calculations using ultrasoft pseudopotentials with a plane-wave basis method and with the generalized gradient approximation (GGA). It is shown that the shape of the formed nanostructures is primarily determined by the anisotropic activation energy and, as the latter is lowered, there is a shape change from wire to pillar. A simulation model of diffusion using the Monte Carlo method is applied in the 3-D (dimensional) case to show how the anisotropic activation energy influences the growth process of the alpha-Fe(2)O(3) nanostructure. The present study provides a way to control the shape of the nanostructures grown by the thermal-oxidation method. PMID- 22071719 TI - Land use and wetland spatial position jointly determine amphibian parasite communities. AB - Land use change is one of the most commonly cited contributing factors to infectious disease emergence, yet the mechanisms responsible for such changes and the spatial scales at which they operate are rarely identified. The distributions of parasites with complex life cycles depend on interactions between multiple host species, suggesting the net effects of land use on infection patterns may be difficult to predict a priori. Here, we used an information-theoretic approach to evaluate the importance of land use and spatial scale (local, watershed, and regional) in determining the presence and abundance of multi-host trematodes of amphibians. Among 40 wetlands and 160 hosts sampled, trematode abundance, species richness, and the presence and abundance of pathogenic species were strongly influenced by variables at the watershed and regional scales. Based on model averaging results, overall parasite richness and abundance were higher in forested wetlands than in agricultural areas; however, this pattern was influenced by a wetland's proximity to the Mississippi Flyway at the regional scale. These patterns likely reflect the activity of trematode definitive hosts, such as mammals and especially birds, such that infections decreased with increasing distance from the Mississippi River. Interestingly, despite lower mean infections, agricultural wetlands had higher variances and maximum infections. At the wetland scale, phosphorus concentrations and the abundances of intermediate hosts, such as snails and larval amphibians, positively affected parasite distributions. Taken together, these results contribute to our understanding of how altered landscapes affect parasite communities and inform further research on the environmental drivers of amphibian parasite infections. PMID- 22071721 TI - Innovative vision. PMID- 22071720 TI - Phylogeny, life history, and ecology contribute to differences in amphibian susceptibility to ranaviruses. AB - Research that identifies the potential host range of generalist pathogens as well as variation in host susceptibility is critical for understanding and predicting the dynamics of infectious diseases within ecological communities. Ranaviruses have been linked to amphibian die-off events worldwide with the greatest number of reported mortality events occurring in the United States. While reports of ranavirus-associated mortality events continue to accumulate, few data exist comparing the relative susceptibility of different species. Using a series of laboratory exposure experiments and comparative phylogenetics, we compared the susceptibilities of 19 amphibian species from two salamander families and five anurans families for two ranavirus isolates: frog virus 3 (FV3) and an FV3-like isolate from an American bullfrog culture facility. We discovered that ranaviruses were capable of infecting 17 of the 19 larval amphibian species tested with mortality ranging from 0 to 100%. Phylogenetic comparative methods demonstrated that species within the anuran family Ranidae were generally more susceptible to ranavirus infection compared to species from the other five families. We also found that susceptibility to infection was associated with species that breed in semi-permanent ponds, develop rapidly as larvae, and have limited range sizes. Collectively, these results suggest that phylogeny, life history characteristics, and habitat associations of amphibians have the potential to impact susceptibility to ranaviruses. PMID- 22071722 TI - Academic freedom. PMID- 22071723 TI - Hubble cleared. PMID- 22071724 TI - The road to fraud starts with a single step. PMID- 22071738 TI - Time is running out for the leap second. PMID- 22071737 TI - Fresh dispute about MMR 'fraud'. PMID- 22071739 TI - Palestinian membership puts UN projects at risk. PMID- 22071740 TI - A struggle for power. PMID- 22071742 TI - Aid organizations tap into social-science expertise. PMID- 22071743 TI - The pollinator crisis: What's best for bees. PMID- 22071744 TI - Seth Stein: The quake killer. PMID- 22071745 TI - Lost in translation: Mystery of the missing text solved. PMID- 22071750 TI - Tropical forests: Still vital when degraded. PMID- 22071751 TI - Nobels: Fundamental biology misses out. PMID- 22071752 TI - Nobels: Maintaining Israel's record. PMID- 22071753 TI - Nobels: Toll pioneers deserve recognition. PMID- 22071754 TI - Tropical forests: Include Congo basin. PMID- 22071755 TI - Tropical forests: Try holistic conservation. PMID- 22071756 TI - Scientists as capitalists: More than one fund for US entrepreneurs. PMID- 22071757 TI - HPV vaccination: Clarifying the use of 'prepubescent'. PMID- 22071758 TI - Evolutionary biology: The path to sociality. PMID- 22071759 TI - Planetary science: Ancient lunar dynamo. PMID- 22071760 TI - Animal behaviour: Why promiscuity pays. PMID- 22071762 TI - Ageing: Old cells under attack. PMID- 22071763 TI - Nanotechnology: A molecular four-wheel drive. PMID- 22071764 TI - Two types of luminescence blinking revealed by spectroelectrochemistry of single quantum dots. AB - Photoluminescence blinking--random switching between states of high (ON) and low (OFF) emissivities--is a universal property of molecular emitters found in dyes, polymers, biological molecules and artificial nanostructures such as nanocrystal quantum dots, carbon nanotubes and nanowires. For the past 15 years, colloidal nanocrystals have been used as a model system to study this phenomenon. The occurrence of OFF periods in nanocrystal emission has been commonly attributed to the presence of an additional charge, which leads to photoluminescence quenching by non-radiative recombination (the Auger mechanism). However, this 'charging' model was recently challenged in several reports. Here we report time-resolved photoluminescence studies of individual nanocrystal quantum dots performed while electrochemically controlling the degree of their charging, with the goal of clarifying the role of charging in blinking. We find that two distinct types of blinking are possible: conventional (A-type) blinking due to charging and discharging of the nanocrystal core, in which lower photoluminescence intensities correlate with shorter photoluminescence lifetimes; and a second sort (B-type), in which large changes in the emission intensity are not accompanied by significant changes in emission dynamics. We attribute B-type blinking to charge fluctuations in the electron-accepting surface sites. When unoccupied, these sites intercept 'hot' electrons before they relax into emitting core states. Both blinking mechanisms can be electrochemically controlled and completely suppressed by application of an appropriate potential. PMID- 22071765 TI - Electrically driven directional motion of a four-wheeled molecule on a metal surface. AB - Propelling single molecules in a controlled manner along an unmodified surface remains extremely challenging because it requires molecules that can use light, chemical or electrical energy to modulate their interaction with the surface in a way that generates motion. Nature's motor proteins have mastered the art of converting conformational changes into directed motion, and have inspired the design of artificial systems such as DNA walkers and light- and redox-driven molecular motors. But although controlled movement of single molecules along a surface has been reported, the molecules in these examples act as passive elements that either diffuse along a preferential direction with equal probability for forward and backward movement or are dragged by an STM tip. Here we present a molecule with four functional units--our previously reported rotary motors--that undergo continuous and defined conformational changes upon sequential electronic and vibrational excitation. Scanning tunnelling microscopy confirms that activation of the conformational changes of the rotors through inelastic electron tunnelling propels the molecule unidirectionally across a Cu(111) surface. The system can be adapted to follow either linear or random surface trajectories or to remain stationary, by tuning the chirality of the individual motor units. Our design provides a starting point for the exploration of more sophisticated molecular mechanical systems with directionally controlled motion. PMID- 22071766 TI - A long-lived lunar dynamo driven by continuous mechanical stirring. AB - Lunar rocks contain a record of an ancient magnetic field that seems to have persisted for more than 400 million years and which has been attributed to a lunar dynamo. Models of conventional dynamos driven by thermal or compositional convection have had difficulty reproducing the existence and apparently long duration of the lunar dynamo. Here we investigate an alternative mechanism of dynamo generation: continuous mechanical stirring arising from the differential motion, due to Earth-driven precession of the lunar spin axis, between the solid silicate mantle and the liquid core beneath. We show that the fluid motions and the power required to drive a dynamo operating continuously for more than one billion years and generating a magnetic field that had an intensity of more than one microtesla 4.2 billion years ago are readily obtained by mechanical stirring. The magnetic field is predicted to decrease with time and to shut off naturally when the Moon recedes far enough from Earth that the dissipated power is insufficient to drive a dynamo; in our nominal model, this occurred at about 48 Earth radii (2.7 billion years ago). Thus, lunar palaeomagnetic measurements may be able to constrain the poorly known early orbital evolution of the Moon. This mechanism may also be applicable to dynamos in other bodies, such as large asteroids. PMID- 22071767 TI - An impact-driven dynamo for the early Moon. AB - The origin of lunar magnetic anomalies remains unresolved after their discovery more than four decades ago. A commonly invoked hypothesis is that the Moon might once have possessed a thermally driven core dynamo, but this theory is problematical given the small size of the core and the required surface magnetic field strengths. An alternative hypothesis is that impact events might have amplified ambient fields near the antipodes of the largest basins, but many magnetic anomalies exist that are not associated with basin antipodes. Here we propose a new model for magnetic field generation, in which dynamo action comes from impact-induced changes in the Moon's rotation rate. Basin-forming impact events are energetic enough to have unlocked the Moon from synchronous rotation, and we demonstrate that the subsequent large-scale fluid flows in the core, excited by the tidal distortion of the core-mantle boundary, could have powered a lunar dynamo. Predicted surface magnetic field strengths are on the order of several microteslas, consistent with palaeomagnetic measurements, and the duration of these fields is sufficient to explain the central magnetic anomalies associated with several large impact basins. PMID- 22071770 TI - Antarctic accumulation seasonality. AB - The resemblance of the orbitally filtered isotope signal from the past 340 kyr in Antarctic ice cores to Northern Hemisphere summer insolation intensity has been used to suggest that the northern hemisphere may drive orbital-scale global climate changes. A recent Letter by Laepple et al. suggests that, contrary to this interpretation, this semblance may instead be explained by weighting the orbitally controlled Antarctic seasonal insolation cycle with a static (present day) estimate of the seasonal cycle of accumulation. We suggest, however, that both time variability in accumulation seasonality and alternative stable seasonality can markedly alter the weighted insolation signal. This indicates that, if the last 340 kyr of Antarctic accumulation has not always looked like the estimate of precipitation and accumulation seasonality made by Laepple et al., this particular accumulation weighting explanation of the Antarctic orbital scale isotopic signal might not be robust. PMID- 22071768 TI - Stepwise evolution of stable sociality in primates. AB - Although much attention has been focused on explaining and describing the diversity of social grouping patterns among primates, less effort has been devoted to understanding the evolutionary history of social living. This is partly because social behaviours do not fossilize, making it difficult to infer changes over evolutionary time. However, primate social behaviour shows strong evidence for phylogenetic inertia, permitting the use of Bayesian comparative methods to infer changes in social behaviour through time, thereby allowing us to evaluate alternative models of social evolution. Here we present a model of primate social evolution, whereby sociality progresses from solitary foraging individuals directly to large multi-male/multi-female aggregations (approximately 52 million years (Myr) ago), with pair-living (approximately 16 Myr ago) or single-male harem systems (approximately 16 Myr ago) derivative from this second stage. This model fits the data significantly better than the two widely accepted alternatives (an unstructured model implied by the socioecological hypothesis or a model that allows linear stepwise changes in social complexity through time). We also find strong support for the co-evolution of social living with a change from nocturnal to diurnal activity patterns, but not with sex-biased dispersal. This supports suggestions that social living may arise because of increased predation risk associated with diurnal activity. Sociality based on loose aggregation is followed by a second shift to stable or bonded groups. This structuring facilitates the evolution of cooperative behaviours and may provide the scaffold for other distinctive anthropoid traits including coalition formation, cooperative resource defence and large brains. PMID- 22071772 TI - Redox imbalance of red blood cells impacts T lymphocyte homeostasis: implication in carotid atherosclerosis. AB - Oxidative stress and immune/inflammatory responses are key pathogenetic factors of atherosclerotic disease. In this contest, mechanisms that regulate survival and death of immune cells may be relevant. Previous studies have demonstrated that red blood cells (RBCs) are physiologically able to inhibit apoptosis and to promote proliferation of activated T lymphocytes from healthy subjects. The aim of the present study was to evaluate whether RBCs from patients with carotid atherosclerosis maintain their property to modulate T cell homeostasis. Peripheral blood lymphocytes (PBLs) obtained from healthy subjects were activated in vitro by phytohemagglutinin in the presence/absence of RBCs from patients with carotid atherosclerosis or of in vitro oxidised RBCs from healthy subjects. Levels of reactive oxygen species (ROS) and aging markers of RBCs as well as susceptibility to apoptosis of PBLs were evaluated by flow cytometry. PBL proliferation was evaluated by 3H-methyl-thymidine incorporation assay whereas secretion of cytokines, analysed in view of their key role in T cell function, was assessed by ELISA. Levels of ROS and phosphatidyl-serine externalisation, a sign of RBC aging, resulted significantly higher in RBCs from patients than in those from healthy subjects, whereas surface glycophorin A expression and reduced glutathione content did the opposite. Unlike RBCs obtained from healthy subjects, RBCs from patients and in vitro oxidised RBCs did not protect activated T lymphocytes from apoptosis. Hence, RBCs from patients with carotid atherosclerosis, probably due to their oxidative imbalance, impact T cell integrity and function. Our results suggest a new regulatory role for RBCs in atherosclerosis. PMID- 22071773 TI - The application of statistical methods using VOCs to identify patients with lung cancer. AB - In this work, an attempt was made to determine a group of lung cancer biomarkers. For this study, breath samples collected from 137 patients with confirmed lung cancer were analyzed by the SPME-GC/MS method. As a reference group, exhaled air from 143 healthy volunteers with different smoking habits (active smokers, passive smokers and nonsmokers) was applied. Statistical methods such as discriminant analysis (DA) and the CHAID model tree were used for data processing and evaluation. In the breath of patients with lung cancer, increased concentration of ethanol, acetone, butane, dimethyl sulfide, isoprene, propanal, 1-propanol, 2-pentanone, furan, o-xylene and ethylbenzene was observed in comparison to healthy nonsmokers. Furthermore, pentanal, hexanal and nonane were identified only in the breath of people who suffered from cancer. DA confirmed the importance of these compounds and allowed us to identify patients with lung cancer from healthy volunteers. In the exhaled air of healthy smokers (passive and active), a higher concentration of acetonitrile, benzene and furan derivatives was observed than in nonsmokers. DA revealed that in order to recognize healthy volunteers with different smoking habits by breath analysis, butyrolactone, carbon disulfide and dimethyl sulfide have to be considered. PMID- 22071774 TI - Association of variants in BAT1-LTA-TNF-BTNL2 genes within 6p21.3 region show graded risk to leprosy in unrelated cohorts of Indian population. AB - Host immune response against Mycobacterium leprae plays an important role in providing resistance to infection and disease progression. Genome-wide linkage and association studies suggest the possibility of multiple risk loci within HLA (6p21.3) region. Any systematic study of relevance within the histocompatibility complex of importance in host immune response would be pertinent because of non replication of the known loci and unavailable information on some of the unexplored genes and regions. A systematic scan was performed of the selected region involving LTA-TNF-LTB genes within 6p21.3 with a resolution of 1SNP/127 bp; and the SNPs in flanking BAT1, NFKBIL and BTNL2-DRA genes on the basis of their tag status or their presence in promoter/exonic regions with MAF of >5%. Nine SNPs located in BAT1, LTA, TNF genes and BTNL2-DRA interval showed strong association with leprosy susceptibility in two independent sets of North Indian population which was replicated in a geographically distinct East Indian population. Conditional logistic regression showed at least one functional SNP remaining significant in each gene, suggesting an independent role of each of the disease associated SNPs. In vitro reporter assay revealed that two SNPs located at BAT1 promoter and 13 kb upstream to LTA gene affected the transcription factor binding site, hence the gene expression. We unravel the role of unexplored immunologically important genes, BAT1 and BTNL2, in addition to known LTA and TNF genes, and the haplotypes of the significantly associated SNPs therein, to understand susceptibility to the disease, leprosy and its differential severity. PMID- 22071775 TI - Comment on: Stenting versus aggressive medical therapy for intracranial arterial stenosis : Chimowitz MI, Lynn MJ, Derdeyn CP, et al. N Engl J Med. 2011;365:993 1003. PMID- 22071776 TI - Percutaneous stereotactic radiofrequency ablation of colorectal liver metastases. AB - OBJECTIVES: To evaluate the outcome of patients with colorectal liver metastasis (CRLM) treated with stereotactic radiofrequency ablation (SRFA). METHODS: Following IRB approval, a retrospective evaluation of 98 SRFA treatment sessions of 189 CRLMs in 63 consecutive patients was performed. Local recurrence rate (LR), overall survival (OS) and disease-free survival (DFS) were analysed. RESULTS: LR was identified in 16% of the tumours (31/189), with no significant differences (P = 0.635) when comparing tumour sizes <3 cm (17.7%), 3-5 cm (11.1%) and >5 cm (17.4%). The median OS from SRFA treatment was 33.2 months after a mean follow-up of 25 months (range 2-66); the corresponding 1-, 3- and 5- year survival rates were 87%, 44% and 27%. The median OS was significantly different when comparing unresectable and resectable patients (27 vs. 58 months, P = 0.002) with OS rates of 92%, 66% and 48% at 1, 3 and 5 years in resectable patients. Tumour size did not affect OS and DFS. CONCLUSION: Due to the favourable outcome, SRFA challenges resection as first-line local treatment of patients with CRLM. As long as randomised studies are pending, we recommend entering an individual decision-making process with every patient. KEY POINTS: Large colorectal liver metastases can be effectively treated by stereotactic radiofrequency ablation (SRFA). Using SRFA the overall survival is not affected by tumour size. SRFA achieves similar overall and disease-free survival rates as surgical resection. SRFA challenges surgical resection as the first-line treatment for colorectal liver metastases. PMID- 22071778 TI - Increase in perceived case suspiciousness due to local contrast optimisation in digital screening mammography. AB - OBJECTIVES: To determine the influence of local contrast optimisation on diagnostic accuracy and perceived suspiciousness of digital screening mammograms. METHODS: Data were collected from a screening region in the Netherlands and consisted of 263 digital screening cases (153 recalled,110 normal). Each case was available twice, once processed with a tissue equalisation (TE) algorithm and once with local contrast optimisation (PV). All cases had digitised previous mammograms. For both algorithms, the probability of malignancy of each finding was scored independently by six screening radiologists. Perceived case suspiciousness was defined as the highest probability of malignancy of all findings of a radiologist within a case. Differences in diagnostic accuracy of the processing algorithms were analysed by comparing the areas under the receiver operating characteristic curves (A(z)). Differences in perceived case suspiciousness were analysed using sign tests. RESULTS: There was no significant difference in A(z) (TE: 0.909, PV 0.917, P = 0.46). For all radiologists, perceived case suspiciousness using PV was higher than using TE more often than vice versa (ratio: 1.14-2.12). This was significant (P <0.0083) for four radiologists. CONCLUSIONS: Optimisation of local contrast by image processing may increase perceived case suspiciousness, while diagnostic accuracy may remain similar. KEY POINTS: Variations among different image processing algorithms for digital screening mammography are large. Current algorithms still aim for optimal local contrast with a low dynamic range. Although optimisation of contrast may increase sensitivity, diagnostic accuracy is probably unchanged. Increased local contrast may render both normal and abnormal structures more conspicuous. PMID- 22071777 TI - Dynamic contrast-enhanced micro-CT on mice with mammary carcinoma for the assessment of antiangiogenic therapy response. AB - OBJECTIVE: To evaluate the potential of in vivo dynamic contrast-enhanced micro computed tomography (DCE micro-CT) for the assessment of antiangiogenic drug therapy response of mice with mammary carcinoma. METHODS: 20 female mice with implanted MCF7 tumours were split into control group and therapy group treated with a known effective antiangiogenic drug. All mice underwent DCE micro-CT for the 3D analysis of functional parameters (relative blood volume [rBV], vascular permeability [K], area under the time-enhancement curve [AUC]) and morphology. All parameters were determined for total, peripheral and central tumour volumes of interest (VOIs). Immunohistochemistry was performed to characterise tumour vascularisation. 3D dose distributions were determined. RESULTS: The mean AUCs were significantly lower in therapy with P values of 0.012, 0.007 and 0.023 for total, peripheral and central tumour VOIs. K and rBV showed significant differences for the peripheral (P(per)(K) = 0.032, P(per) (rBV) = 0.029), but not for the total and central tumour VOIs (P(total)(K) = 0.108, P(central)(K) = 0.246, P(total) (rBV) = 0.093, P(central) (rBV) = 0.136). Mean tumour volume was significantly smaller in therapy (P (in vivo) = 0.001, P (ex vivo) = 0.005). Histology revealed greater vascularisation in the controls and central tumour necrosis. Doses ranged from 150 to 300 mGy. CONCLUSIONS: This study indicates the great potential of DCE micro-CT for early in vivo assessment of antiangiogenic drug therapy response. KEY POINTS: Dynamic contrast enhanced micro-CT (computed tomography) is a new experimental laboratory technique. DCE micro-CT allows early in vivo assessment of antiangiogenic drug therapy response. Pharmaceutical drugs can be tested before translation to clinical practice. Both morphological and functional parameters can be obtained using DCE micro-CT. Antiangiogenic effects can be visualised with DCE micro-CT. PMID- 22071779 TI - Switching of +/- 360 degrees domain wall states in a nanoring by an azimuthal Oersted field. AB - We demonstrate magnetic switching between two 360 degrees domain wall vortex states in cobalt nanorings, which are candidate magnetic states for robust and low power magnetoresistive random access memory (MRAM) devices. These 360 degrees domain wall (DW) or 'twisted onion' states can have clockwise or counterclockwise circulation, the two states for data storage. Reliable switching between the states is necessary for any realistic device. We accomplish this switching by applying a circular Oersted field created by passing current through a metal atomic force microscope tip placed at the center of the ring. After initializing in an onion state, we rotate the DWs to one side of the ring by passing a current through the center, and can switch between the two twisted states by reversing the current, causing the DWs to split and meet again on the opposite side of the ring. A larger current will annihilate the DWs and create a perfect vortex state in the rings. PMID- 22071781 TI - Lung adenocarcinomas with HER2-activating mutations are associated with distinct clinical features and HER2/EGFR copy number gains. AB - INTRODUCTION: A fraction of lung adenocarcinomas harbor activating mutations in the HER2 kinase domain. HER2-targeted therapies have shown minimal benefit in molecularly unselected patients. We investigated clinical and potential molecular factors associated with HER2-mutant lung adenocarcinoma. METHODS: A total of 224 lung adenocarcinoma samples were examined for activating mutations in epidermal growth factor receptor (EGFR; exons 18-22), V-Ki-ras2 Kirsten rat sarcoma (KRAS; exons 2 and 3), and HER2 (exons 18-21) by direct sequencing. Gene copy number and protein expression of both EGFR and HER2 were further explored in samples harboring HER2 mutations using fluorescence in situ hybridization and immunohistochemistry, respectively. RESULTS: The mutation rates of EGFR, KRAS, HER2 were 63.39% (142/224), 4.46% (10/224), and 3.57% (8/224), respectively. All mutations were mutually exclusive. All eight HER2 mutations occurred in never smokers and seven were in women. The HER2 mutation rate in samples without EGFR and KRAS mutations was 11.11% (8/72). Seven of eight HER2-mutated tumors showed HER2 copy number gains (CNGs) and five showed EGFR CNGs. All of the HER2-mutated samples showed either HER2 or EGFR CNGs. Gene amplification of HER2 and EGFR was mutually exclusive in HER2-mutated samples. CONCLUSION: HER2 mutations in lung adenocarcinoma predominantly occurred in women and never smokers. Most HER2 mutated tumors showed HER2 CNGs. As all of the samples with HER2 mutation showed either HER2 or EGFR CNGs, these patients could potentially benefit from novel EGFR/HER2 dual or pan-erythroblastic leukemia viral oncogene homolog tyrosine kinase inhibitors. PMID- 22071780 TI - Exhaled breath analysis with a colorimetric sensor array for the identification and characterization of lung cancer. AB - INTRODUCTION: The pattern of exhaled breath volatile organic compounds represents a metabolic biosignature with the potential to identify and characterize lung cancer. Breath biosignature-based classification of homogeneous subgroups of lung cancer may be more accurate than a global breath signature. Combining breath biosignatures with clinical risk factors may improve the accuracy of the signature. OBJECTIVES: To develop an exhaled breath biosignature of lung cancer using a colorimetric sensor array and to determine the accuracy of breath biosignatures of lung cancer characteristics with and without the inclusion of clinical risk factors. METHODS: The exhaled breath of 229 study subjects, 92 with lung cancer and 137 controls, was drawn across a colorimetric sensor array. Logistic prediction models were developed and statistically validated based on the color changes of the sensor. Age, sex, smoking history, and chronic obstructive pulmonary disease were incorporated in the prediction models. RESULTS: The validated prediction model of the combined breath and clinical biosignature was moderately accurate at distinguishing lung cancer from control subjects (C-statistic 0.811). The accuracy improved when the model focused on only one histology (C-statistic 0.825-0.890). Individuals with different histologies could be accurately distinguished from one another (C-statistic 0.864 for adenocarcinoma versus squamous cell carcinoma). Moderate accuracies were noted for validated breath biosignatures of stage and survival (C-statistic 0.785 and 0.693, respectively). CONCLUSIONS: A colorimetric sensor array is capable of identifying exhaled breath biosignatures of lung cancer. The accuracy of breath biosignatures can be optimized by evaluating specific histologies and incorporating clinical risk factors. PMID- 22071783 TI - Modest improvements of survival for patients with small cell lung cancer aged 45 to 59 years only, diagnosed in the Netherlands, 1989 to 2008. AB - INTRODUCTION: Lung cancer was a major epidemic in the last decades; 10 to 15% of lung cancer consists of small cell lung cancer (SCLC). Several changes in the diagnostic and treatment procedures took place during the last 20 years. This article focuses on trends in incidence, treatment, and survival of SCLC observed since the 1990 s. METHODS: All cases with SCLC diagnosed in 1989 to 2009 in the Netherlands were included (n = 34,100). Follow-up was complete until January 1, 2010. RESULTS: The proportion of patients with extensive disease increased from 47 to 63%. The proportion of patients with limited disease receiving chemoradiation increased from 22% in 1989 to 2003 to 72% in 2004 to 2009 among those younger than 45 to 59 years, from 15 to 58% among those aged 60 to 74 years, and from 7 to 27% among those 75 years or older. Among patients with extensive disease, the proportion receiving chemotherapy remained stable over time (84, 75, and almost 50% for the above mentioned age groups, respectively). Significant improvements in 1-year relative survival occurred for patients aged 45 to 59 years, but not for the other age groups. Relative survival has significantly increased for both stage groups. CONCLUSION: Improved staging resulted in improved survival for both stage groups, whereas survival of the total group has only significantly improved for patients aged 45 to 59 years. The latter is possibly related with improved treatment strategies. As survival is still very poor, prevention of lung cancer remains important. PMID- 22071782 TI - Results of a multicentric in silico clinical trial (ROCOCO): comparing radiotherapy with photons and protons for non-small cell lung cancer. AB - INTRODUCTION: This multicentric in silico trial compares photon and proton radiotherapy for non-small cell lung cancer patients. The hypothesis is that proton radiotherapy decreases the dose and the volume of irradiated normal tissues even when escalating to the maximum tolerable dose of one or more of the organs at risk (OAR). METHODS: Twenty-five patients, stage IA-IIIB, were prospectively included. On 4D F18-labeled fluorodeoxyglucose-positron emission tomography-computed tomography scans, the gross tumor, clinical and planning target volumes, and OAR were delineated. Three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) photon and passive scattered conformal proton therapy (PSPT) plans were created to give 70 Gy to the tumor in 35 fractions. Dose (de-)escalation was performed by rescaling to the maximum tolerable dose. RESULTS: Protons resulted in the lowest dose to the OAR, while keeping the dose to the target at 70 Gy. The integral dose (ID) was higher for 3DCRT (59%) and IMRT (43%) than for PSPT. The mean lung dose reduced from 18.9 Gy for 3DCRT and 16.4 Gy for IMRT to 13.5 Gy for PSPT. For 10 patients, escalation to 87 Gy was possible for all 3 modalities. The mean lung dose and ID were 40 and 65% higher for photons than for protons, respectively. CONCLUSIONS: The treatment planning results of the Radiation Oncology Collaborative Comparison trial show a reduction of ID and the dose to the OAR when treating with protons instead of photons, even with dose escalation. This shows that PSPT is able to give a high tumor dose, while keeping the OAR dose lower than with the photon modalities. PMID- 22071784 TI - Dual IHC and FISH testing for ALK gene rearrangement in lung adenocarcinomas in a routine practice: a French study. AB - INTRODUCTION: In 2011, the French National Cancer Institute recommended ALK fluorescence in situ hybridization (FISH) testing in all EGFR/KRAS-negative adenocarcinomas by all the hospital molecular genetics platforms of cancers; however, this technique remains time and cost consuming and not suitable for a large-scale screening, in contrast to immunohistochemistry (IHC). METHODS: To evaluate IHC as a prescreening tool, 441 specimens, including small biopsies and surgical specimens, were analyzed prospectively on the Grenoble molecular genetics platform. EGFR and KRAS mutation analyses and ALK IHC, using the 5A4 mAb on an automated staining module, were performed on all specimens; 100 were tested by both ALK IHC and FISH (break-apart probe). RESULTS: Twenty-seven cases out of 441 were strongly positive (3+ intensity in more than 60% of cells) with ALK mAb, two additional cases exhibited a faint staining (1+) in less than 30% of the cells. Among the 100 cases analyzed by IHC and FISH, 19 were not interpretable by FISH, but 21 were positive with both techniques. Sensitivity and specificity of IHC when compared with FISH were 95 and 100%, respectively. Eleven patients were included in crizotinib trials. Among the 352 analyzable specimens for mutations, 7% were EGFR and 29% were KRAS mutated. CONCLUSIONS: Our IHC protocol, using a commercially available antibody and an amplification step on an automated staining module, led to intense cytoplasmic staining in 6.5% of the adenocarcinomas screened. Our results favor ALK IHC prescreening on a daily routine on surgical specimens and on small biopsies before FISH testing. PMID- 22071786 TI - DeltaNp63 (p40) and thyroid transcription factor-1 immunoreactivity on small biopsies or cellblocks for typing non-small cell lung cancer: a novel two-hit, sparing-material approach. AB - INTRODUCTION: Diagnosing non-small cell lung cancer on biopsy/cellblock samples by morphology may be demanding. As sparing material for molecular testing is mandatory, a minimalist immunohistochemistry (IHC)-based diagnostic approach is warranted by means of novel, reliable, and easy-to-assess biomarkers. METHODS: Forty-six consecutive biopsy/cellblock samples and the corresponding resection specimens (as the gold standard for morphology and IHC) from 30 adenocarcinomas (AD), 10 squamous carcinomas (SQC), 5 adenosquamous carcinomas (ADSQC), and 1 sarcomatoid carcinoma (SC) were IHC-evaluated for p40 [corresponding to nontransactivating DeltaNp63 isoforms] and thyroid transcription factor-1 (TTF1) by semiquantitative assessment. For p40, also immunodecoration intensity was taken into account and dichotomized as strong or low. RESULTS: Nonrandom and overlapping distributions of the relevant markers were found in biopsy/cellblock and surgical specimens, which closely correlated with each other and the diverse tumor categories, with no differences in area under curve-receiver-operating characteristic curves for each marker between any two samples, including p40 and p63. Diagnostic combinations were p40-/TTF1+ or TTF1- for AD (where p40 was negative, apart from 5/30 AD showing at the best 1-2% tumor cells with low intensity); p40+/TTF1- (p40 strong and by far higher than 50%) for SQC; and p40+/TTF1+ or p40+/TTF1- (p40 strong and less than 50%) for ADSQC. The single SC case was p40-/TTF1-, suggesting glandular lineage. Practically, 41/46 (89%) tumors were correctly classified by IHC on small samples, including 30 AD, 10 SQC, 1/5 ADSQC, and no SC. Underdiagnosis of ADSQC was actually because of sampling error of biopsies/cellblocks rather than insufficient biomarker robustness, whereas underdiagnosis of SC was really because of the failure of either marker to highlight epithelial-mesenchymal transition. CONCLUSIONS: This minimalist IHC-based model of p40 and TTF1 on biopsy/cellblock samples was effective to correctly subtype most cases of lung cancer. PMID- 22071785 TI - Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer. AB - INTRODUCTION: TSU-68 is an oral small-molecule inhibitor that targets vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor beta, and fibroblast growth factor receptor 1. An open-label, single-arm, phase I study was performed to evaluate escalating doses of TSU-68 in combination with standard chemotherapy in patients with advanced non-small cell lung cancer. METHODS: Eligible patients received TSU-68 at 200 or 400 mg twice daily and continuously in combination with carboplatin (area under the curve, 6 mg . min/mL) plus paclitaxel (200 mg/m2) on day 1 every 21 days. RESULTS: Thirty-seven patients were enrolled at the two dose levels of TSU-68. No dose-limiting toxicities were observed with TSU-68 at the 200 mg twice a day dose level. At 400 mg twice a day, one of six patients experienced a dose-limiting toxicity (anorexia of grade 3) during the first cycle. The 400 mg twice a day dose level was determined to be the recommended dose, and a total of 34 patients were treated at this dose. Overall, adverse events were mild to moderate in severity, with the most frequently observed such events being myelosuppression, neuropathy, and gastrointestinal disorders. No drug-related bleeding was observed. The objective response rate was 39.4% (95% confidence interval, 22.9-57.9%), and median progression-free survival was 5.6 months (95% confidence interval, 3.6-7.2 months). Coadministration of TSU-68, carboplatin, and paclitaxel had no substantial impact on the pharmacokinetics of these drugs. CONCLUSIONS: TSU-68 can be safely combined with standard doses of carboplatin-paclitaxel, with the combination manifesting promising antitumor activity. PMID- 22071787 TI - Urine utilisation by microbial fuel cells; energy fuel for the future. AB - This communication reports for the first time the direct utilisation of urine in MFCs for the production of electricity. Different conversion efficiencies were recorded, depending on the amount treated. Elements such as N, P, K can be locked into new biomass, thus removed from solution, resulting in recycling without environmental pollution. PMID- 22071788 TI - Behavioral and physiological responses to child-directed speech of children with autism spectrum disorders or typical development. AB - Young boys with autism were compared to typically developing boys on responses to nonsocial and child-directed speech (CDS) stimuli. Behavioral (looking) and physiological (heart rate and respiratory sinus arrhythmia) measures were collected. Boys with autism looked equally as much as chronological age-matched peers at nonsocial stimuli, but less at CDS stimuli. Boys with autism and language age-matched peers differed in patterns of looking at live versus videotaped CDS stimuli. Boys with autism demonstrated faster heart rates than chronological age-matched peers, but did not differ significantly on respiratory sinus arrhythmia. Reduced attention during CDS may restrict language-learning opportunities for children with autism. The heart rate findings suggest that young children with autism have a nonspecific elevated arousal level. PMID- 22071789 TI - Negative correlation between expression level and evolutionary rate of long intergenic noncoding RNAs. AB - Mammalian genomes contain numerous genes for long noncoding RNAs (lncRNAs). The functions of the lncRNAs remain largely unknown but their evolution appears to be constrained by purifying selection, albeit relatively weakly. To gain insights into the mode of evolution and the functional range of the lncRNA, they can be compared with much better characterized protein-coding genes. The evolutionary rate of the protein-coding genes shows a universal negative correlation with expression: highly expressed genes are on average more conserved during evolution than the genes with lower expression levels. This correlation was conceptualized in the misfolding-driven protein evolution hypothesis according to which misfolding is the principal cost incurred by protein expression. We sought to determine whether long intergenic ncRNAs (lincRNAs) follow the same evolutionary trend and indeed detected a moderate but statistically significant negative correlation between the evolutionary rate and expression level of human and mouse lincRNA genes. The magnitude of the correlation for the lincRNAs is similar to that for equal-sized sets of protein-coding genes with similar levels of sequence conservation. Additionally, the expression level of the lincRNAs is significantly and positively correlated with the predicted extent of lincRNA molecule folding (base-pairing), however, the contributions of evolutionary rates and folding to the expression level are independent. Thus, the anticorrelation between evolutionary rate and expression level appears to be a general feature of gene evolution that might be caused by similar deleterious effects of protein and RNA misfolding and/or other factors, for example, the number of interacting partners of the gene product. PMID- 22071790 TI - A model for the effect of homologous recombination on microbial diversification. AB - The effect of homologous recombination (HR) on the evolution of microbial genomes remains contentious as competing hypotheses seek to explain the evolutionary dynamics of microbial species. Evidence for HR between microbial genomes is widespread, and this process has been proposed to act as a cohesive force that can constrain the diversification of microbial lineages. We seek to characterize the evolutionary dynamics of sympatric populations to explore the impact of HR on microbial speciation. We describe a simple equation for quantifying the cohesive effect of HR on microbial populations as a function of their nucleotide divergence, MU/rho=pig10(-20 pig). The model was verified using a forward-time microbial population simulator that can explore the evolutionary dynamics of sympatric populations in nonoverlapping niche space. The model was also evaluated using multilocus sequence data from a range of microbial species, providing criteria for dividing them into either cohesively recombining or clonally diverging lineages. We conclude that models of microbial diversification that appear contradictory can be explained in a unified manner as the natural and predictable consequence of variation in a small number of population parameters. PMID- 22071791 TI - Multifocal presentation of medulloblastoma in adulthood. AB - Medulloblastoma in adulthood is uncommon but not rare; annual incidence is 2 20/1,000,000. Some peculiarities characterize medulloblastoma in adult patients compared with the child type: lateral cerebellar location, heterogeneous signal intensity on magnetic resonance imaging, desmoplastic histological variant, and more favourable prognosis. Preoperative diagnosis is crucial for correct management of these patients. However, because of the low incidence of medulloblastoma in the adult population, preoperative diagnosis remains challenging and prognostic factors and best treatment options are still controversial. In this setting, some unusual findings, for example multifocal presentation and extra-axial location, can confound diagnosis and make treatment difficult. We present a short case-illustrated review on these remarkable issues. PMID- 22071792 TI - Combined gene expression and protein interaction analysis of dynamic modularity in glioma prognosis. AB - Because of the variety of factors affecting glioma prognosis, prediction of patient survival is particularly difficult. Protein-protein interaction (PPI) networks have been considered with regard to how their spatial characteristics relate to glioma. However, the dynamic nature of PPIs in vivo makes them temporally and spatially complex events. Integration of prognosis-specific co expression information adds further dynamic features to these networks. Although some biomarkers for glioma prognosis have been identified, none is sufficient for accurate prediction of either prognosis or improved survival. We have established co-expressed protein-interaction networks that integrate protein-protein interactions with glioma gene-expression profiles related to different survival times. Biomarkers related to glioma prognosis were identified by comparative analysis of the dynamic features of the glioma prognosis network, particularly subnetworks. Four significantly differently expressed genes (SDEGs) are upregulated and ten SDEGs downregulated as lifetime is extended. In addition, 97 enhanced differently co-expressed protein interactions (DCPIs) and 99 weakened DCPIs were associated with glioma patient lifetime extension. We propose a method for estimating glioma prognosis on the basis of the construction of a dynamic modular network. We have used this method to identify dynamic genes and interactions related to glioma prognosis. Among these, enhanced MYC expression was related to lifetime extension, as were interactions between E2F1 and RB1 and between EGFR and p38. This method is a novel means of studying the molecular mechanisms determining prognosis in glioma. PMID- 22071793 TI - "Visual sensory trick" in patient with cervical dystonia. AB - Sensory tricks are clinical maneuvers that may partially relieve dystonic contractions. Any clinical maneuver that modulates afferent sensory and efferent motor pathways could be used as a sensory trick in patients with cervical dystonia. Although various sensory tricks have been described to reduce cervical dystonia, little is known about the exact mechanisms by which they operate. We report a case of cervical dystonia that was alleviated through the use of a visual-sensory trick. Our findings suggest that visual stimulation might be an effective sensory trick in cervical dystonia by compensating for a defective sensory system, or because visual pathways might be also affected by sensory interactions in cervical dystonia. PMID- 22071794 TI - Concordance between severity of disease, prevalence of nonmotor symptoms, patient reported quality of life and disability and use of medication in Parkinson's disease. AB - The aim of this study was to test the concordance between disease severity, prevalence of nonmotor symptoms, age, health-related quality of life (HRQoL), disability and medication use in patients with Parkinson's disease (PD). Severity was classified with the Hoehn and Yahr (HY) scale and Levodopa Equivalent Daily Dose (LEDD) calculated. HRQoL was evaluated with the SF-36, disability with the WHO-DAS II and nonmotor symptoms with the NMSQuest. Patients were clustered using SF-36 and WHO-DAS II into three groups covering the continuum from low disability and HRQoL, to severe disability and HRQoL decrement. Contingency Coefficient were used to verify the relationships between clusters and HY stage; ANOVA to evaluate differences in NMS, age and LEDD between clusters; odds ratio to test the likelihood of taking levodopa or dopamine agonist and being member of the three clusters; t test to evaluate differences in LEDD between patients with HY >=3 or <=2. Eighty-six patients were clustered: 48 had low disability and HRQoL decrement, 18 intermediate disability and HRQoL decrement and 20 high disability and HRQoL decrement. A significant relationship was found between PD severity groups, HRQoL and disability profiles. No differences for age and LEDD were observed in the three groups, and those with more disability and lower HRQoL reported a higher number of nonmotor symptoms; patients in HY >=3 were prescribed higher doses of drugs. In conclusion, we found a substantial concordance between PD staging, prevalence of nonmotor symptoms and patient-reported HRQoL and disability measures. In our opinion, the SF-36 and the WHO-DAS II can be used for profiling patients. PMID- 22071795 TI - Whole-gland salvage high-intensity focused ultrasound therapy for localized prostate cancer recurrence after external beam radiation therapy. AB - BACKGROUND: Whole-gland high-intensity focused ultrasound (HIFU) has been used as salvage therapy for local recurrence following external beam radiation therapy for decades. This article describes the use of the Sonablate 500 HIFU system in the salvage setting. METHODS: An evaluation was performed of a consecutive group of men with biochemical failure after external beam radiation therapy with histologically proven local recurrence and bone-scan and pelvic magnetic resonance imaging to exclude macroscopic metastases, and who chose to have whole gland salvage HIFU (Sonablate 500) at 2 centers (3 expert HIFU surgeons at each center). The modified Clavien system was used to categorize adverse events and validated questionnaires for functional outcomes. Progression following HIFU treatment was defined as ASTRO-Phoenix criteria (prostate serum antigen [PSA] >nadir+2 ng/mL) and/or a positive biopsy and/or start of hormone therapy. RESULTS: Eighty-four men underwent whole-gland salvage HIFU (2004-2009). Median age, pretreatment serum PSA, and biopsy Gleason score was 68 years (range, 64-72 years), 4.3 ng/mL (range, 1.9-7.9 ng/mL), and 7 (range, 6-7), respectively. Mean follow-up was 19.8 months (range, 3.0-35.1 months). After salvage HIFU, 62% of the men were pad-free and leak-free. Mean International Index of Erectile Function-5 point score fell from 8.8 to 4.7 (P < .001). International Prostate Symptoms Score and RAND-SF36 scores were not affected. Two men developed rectourethral fistulae after 1 salvage procedure. A further 2 fistulae occurred in the 6 men undergoing a second salvage HIFU. Intervention for bladder outlet obstruction was needed in 20% (17 of 84 patients). If PSA nonresponders were included, 1- and 2-year progression-free survival rates were 59% (50 of 84 patients) and 43% (36 of 84 patients), respectively. If PSA nonresponders were excluded, 1- and 2-year progression-free survival rates were 62% (48 of 77 patients) and 48% (37 of 77 patients), respectively. CONCLUSIONS: Salvage whole gland HIFU is a high-risk procedure. Although its use in early cancer control is promising, strategies to better identify metastatic disease prior to salvage therapy and reduce local toxicity are needed to improve on this. PMID- 22071796 TI - Homocysteine and the risk of nursing home admission and mortality in older persons. AB - BACKGROUND/OBJECTIVES: This study aimed to investigate whether higher homocysteine and lower vitamin B12 concentrations increase the risk of future nursing home (NH) admission and all-cause mortality in independently living older persons. SUBJECTS/METHODS: In total, 1117 independently living participants (mean age=75.1, s.d.=6.4) were included in this prospective sub-study of the Longitudinal Aging Study Amsterdam. EDTA plasma samples, collected in 1995-1996, were analysed for total homocysteine (MUmol/l). Time to NH admission was assessed using a follow-up until 2002-2003. In addition, we studied mortality until 1 June 2007. Cox proportional hazards models were used to examine the association between homocysteine in quartiles and risk of NH admission and mortality. RESULTS: During follow-up, 126 persons (11.3%) were admitted to NHs, and 513 persons (45.9%) deceased. In men, no significant associations were observed. In women, after adjustment for confounding, the highest quartile of homocysteine was associated with a significantly higher risk of NH admission compared with the first quartile (hazard ratio (HR)=2.97, 95% confidence interval (CI)=1.36-6.49). Both women in the third and the fourth quartile of homocysteine had a significantly higher mortality risk (HR=1.70, 95% CI=1.08-2.65 and HR=1.91, 95% CI=1.22-3.00, respectively) compared with the first quartile. Vitamin B12 was not related to an increased risk of NH admission and mortality. CONCLUSIONS: Elevated plasma homocysteine is associated with an increased risk of NH admission and mortality in older women, but not in older men. PMID- 22071797 TI - Calcium channel blockers for neuroleptic-induced tardive dyskinesia. AB - BACKGROUND: Schizophrenia and related disorders affect a sizable proportion of any population. Neuroleptic (antipsychotic) medications are the primary treatment for these disorders. Neuroleptic medications are associated with a variety of side effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil) have been among these experimental treatments. OBJECTIVES: To determine the effects of calcium-channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. SEARCH STRATEGY: We updated previous searches in May 2010 by searching the Cochrane Schizophrenia Group Register using the Cochrane Schizophrenia Group search strategy. SELECTION CRITERIA: Randomised clinical trials comparing calcium channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness. DATA COLLECTION AND ANALYSIS: We planned to extract and analyse data on an intention-to-treat (ITT) basis. We intended to calculate the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random effects model, and, where possible, calculate the number needed to treat. We planned to calculate mean differences (MD) for continuous data. MAIN RESULTS: We did not include any trials in this review. We excluded 15 studies; eight were not randomised, one did not use calcium channel blockers, five small, randomised, studies reported no usable data and one did not include people with both tardive dyskinesia and schizophrenia. AUTHORS' CONCLUSIONS: The effects of calcium channel blockers for antipsychotic induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well designed randomised clinical trials. PMID- 22071798 TI - Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants. AB - BACKGROUND: Infants of very low birth weight often receive multiple transfusions of red blood cells, usually in response to predetermined haemoglobin or haematocrit thresholds. In the absence of better indices, haemoglobin levels are imperfect but necessary guides to the need for transfusion. Chronic anaemia in premature infants may, if severe, cause apnoea, poor neurodevelopmental outcomes or poor weight gain.On the other hand, red blood cell transfusion may result in transmission of infections, circulatory or iron overload, or dysfunctional oxygen carriage and delivery. OBJECTIVES: To determine if erythrocyte transfusion administered to maintain low as compared to high haemoglobin thresholds reduces mortality or morbidity in very low birth weight infants enrolled within three days of birth. SEARCH METHODS: Two review authors independently searched the Cochrane Central Register of Controlled Trials (The Cochrane Library) , MEDLINE,EMBASE, and conference proceedings through June 2010. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) comparing the effects of early versus late, or restrictive versus liberal erythrocyte transfusion regimes in low birth weight infants applied within three days of birth, with mortality or major morbidity as outcomes. PMID- 22071799 TI - Human albumin solution for resuscitation and volume expansion in critically ill patients. AB - BACKGROUND: Human albumin solutions are used for a range of medical and surgical problems. Licensed indications are the emergency treatment of shock and other conditions where restoration of blood volume is urgent, such as in burns and hypoproteinaemia. Human albumin solutions are more expensive than other colloids and crystalloids. OBJECTIVES: To quantify the effect on mortality of human albumin and plasma protein fraction (PPF) administration in the management of critically ill patients. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register (searched 31 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (Ovid) (1948 to week 3 May 2011), EMBASE (Ovid) (1980 to Week 21 2011), CINAHL (EBSCO) (1982 to May 2011), ISI Web of Science: Science Citation Index Expanded (SCI EXPANDED) (1970 to May 2011), ISI Web of Science: Conference Proceedings Citation Index - Science (CPCI-S) (1990 to May 2011), PubMed (www.ncbi.nlm.nih.gov/sites/entrez/) (searched 10 June 2011, limit: last 60 days). Reference lists of trials and review articles were checked, and authors of identified trials were contacted. SELECTION CRITERIA: Randomised controlled trials comparing albumin or PPF with no albumin or PPF or with a crystalloid solution in critically ill patients with hypovolaemia, burns or hypoalbuminaemia. DATA COLLECTION AND ANALYSIS: We collected data on the participants, albumin solution used, mortality at the end of follow up, and quality of allocation concealment. Analysis was stratified according to patient type. MAIN RESULTS: We found 38 trials meeting the inclusion criteria and reporting death as an outcome. There were 1,958 deaths among 10,842 trial participants.For hypovolaemia, the relative risk of death following albumin administration was 1.02 (95% confidence interval (CI) 0.92 to 1.13). This estimate was heavily influenced by the results of the SAFE trial, which contributed 75.2% of the information (based on the weights in the meta-analysis). For burns, the relative risk was 2.93 (95% CI 1.28 to 6.72) and for hypoalbuminaemia the relative risk was 1.26 (95% CI 0.84 to 1.88). There was no substantial heterogeneity between the trials in the various categories (Chi(2) = 26.66, df = 31, P = 0.69). The pooled relative risk of death with albumin administration was 1.05 (95% CI 0.95 to 1.16). AUTHORS' CONCLUSIONS: For patients with hypovolaemia, there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as saline. There is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia. The possibility that there may be highly selected populations of critically ill patients in which albumin may be indicated remains open to question. However, in view of the absence of evidence of a mortality benefit from albumin and the increased cost of albumin compared to alternatives such as saline, it would seem reasonable that albumin should only be used within the context of well concealed and adequately powered randomised controlled trials. PMID- 22071800 TI - Teaching critical appraisal skills in healthcare settings. AB - BACKGROUND: Critical appraisal is the process of assessing and interpreting evidence by systematically considering its validity, results and relevance to an individual's work. Within the last decade critical appraisal has been added as a topic to many medical school and UK Royal College curricula, and several continuing professional development ventures have been funded to provide further training. This is an update of a Cochrane review first published in 2001. OBJECTIVES: To assess the effects of teaching critical appraisal skills to health professionals on the process of care, patient outcomes and knowledge of health professionals. SEARCH METHODS. We updated the search (see Appendix 1 for search strategies by database) and used those search strategies to search the Cochrane Central Register of Controlled Trials (1997 to June 2011) and MEDLINE (from 1997 to June 2011). We also searched EMBASE, CINAHL and PsycINFO (up to January 2010). We searched LISA (up to January 2010), ERIC (up to January 2010), SIGLE (up to January 2010) and Web of Knowledge (up to January 2010). We also searched the Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register up to January 2010. SELECTION CRITERIA: Randomised trials, controlled clinical trials, controlled before and after studies and interrupted time series analyses that examined the effectiveness of educational interventions teaching critical appraisal to health professionals. The outcomes included process of care, patient mortality, morbidity, quality of life and satisfaction. We included studies reporting on health professional knowledge/awareness only when based upon objective, standardised, validated instruments. We did not consider studies involving students. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We contacted authors of included studies to obtain missing data. MAIN RESULTS: In total, we reviewed a total of 11,057 titles and abstracts, of which 148 appeared potentially relevant to the review. We included three studies involving 272 people in this review. None of the included studies evaluated process of care or patient outcomes. Statistically significant improvements in participants' knowledge were reported in domains of critical appraisal (variable approaches across studies) in two of the three studies. We determined risk of bias to be 'unclear' and as such considered this to be 'plausible bias that raises some doubt about the results'. AUTHORS' CONCLUSIONS: Low-intensity critical appraisal teaching interventions in healthcare populations may result in modest gains. Improvements to research examining the effectiveness of interventions in healthcare populations are required; specifically rigorous randomised trials employing interventions using appropriate adult learning theories. PMID- 22071801 TI - Antiplatelet agents for intermittent claudication. AB - BACKGROUND: Peripheral arterial disease (PAD) is common and is a marker of systemic atherosclerosis. Patients with symptoms of intermittent claudication (IC) are at increased risk of cardiovascular events (myocardial infarction (MI) and stroke) and of both cardiovascular and all cause mortality. OBJECTIVES: To determine the effectiveness of antiplatelet agents in reducing mortality (all cause and cardiovascular) and cardiovascular events in patients with intermittent claudication. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases group searched their Specialised Register (last searched April 2011) and CENTRAL (2011, Issue 2) for publications on antiplatelet agents and IC. In addition reference lists of relevant articles were also searched. SELECTION CRITERIA: Double-blind randomised controlled trials comparing oral antiplatelet agents versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication were included. Patients with asymptomatic PAD (stage I Fontaine), stage III and IV Fontaine PAD, and those undergoing or awaiting endovascular or surgical intervention were excluded. DATA COLLECTION AND ANALYSIS: Data on methodological quality, participants, interventions and outcomes including all cause mortality, cardiovascular mortality, cardiovascular events, adverse events, pain free walking distance, need for revascularisation, limb amputation and ankle brachial pressure indices were collected. For each outcome, the pooled risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) was calculated. MAIN RESULTS: A total of 12 studies with a combined total of 12,168 patients were included in this review. Antiplatelet agents reduced all cause (RR 0.76, 95% CI 0.60 to 0.98) and cardiovascular mortality (RR 0.54, 95% CI 0.32 to 0.93) in patients with IC compared with placebo. A reduction in total cardiovascular events was not statistically significant (RR 0.80, 95% CI 0.63 to 1.01). Data from two trials (which tested clopidogrel and picotamide respectively against aspirin) showed a significantly lower risk of all cause mortality (RR 0.73, 95% CI 0.58 to 0.93) and cardiovascular events (RR 0.81, 95% CI 0.67 to 0.98) with antiplatelets other than aspirin compared with aspirin. Antiplatelet therapy was associated with a higher risk of adverse events, including gastrointestinal symptoms (dyspepsia) (RR 2.11, 95% CI 1.23 to 3.61) and adverse events leading to cessation of therapy (RR 2.05, 95% CI 1.53 to 2.75) compared with placebo; data on major bleeding (RR 1.73, 95% CI 0.51, 5.83) and on adverse events in trials of aspirin versus alternative antiplatelet were limited. Risk of limb deterioration leading to revascularisation was significantly reduced by antiplatelet treatment compared with placebo (RR 0.65, 95% CI 0.43 to 0.97). AUTHORS' CONCLUSIONS: Antiplatelet agents have a beneficial effect in reducing all cause mortality and fatal cardiovascular events in patients with IC. Treatment with antiplatelet agents in this patient group however is associated with an increase in adverse effects, including GI symptoms, and healthcare professionals and patients need to be aware of the potential harm as well as the benefit of therapy; more data are required on the effect of antiplatelets on major bleeding. Evidence on the effectiveness of aspirin versus either placebo or an alternative antiplatelet agent is lacking. Evidence for thienopyridine antiplatelet agents was particularly compelling and there is an urgent need for multicentre trials to compare the effects of aspirin against thienopyridines. PMID- 22071802 TI - Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature infants less than 1500 grams. AB - BACKGROUND: Milk feedings can be given via nasogastric tube either intermittently, typically over 10 to 20 minutes every two or three hours, or continuously, using an infusion pump. Although theoretical benefits and risks of each method have been proposed, effects on clinically important outcomes remain uncertain. OBJECTIVES: To examine the evidence regarding the effectiveness of continuous versus intermittent bolus nasogastric milk feeding in premature infants less than 1500 grams. SEARCH METHODS: Searches were performed of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2011), MEDLINE, CINAHL and HealthSTAR up to July 2011. SELECTION CRITERIA: Randomised and quasi-randomised clinical trials comparing continuous versus intermittent bolus nasogastric milk feeding in premature infants less than 1500 grams. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for relevance and methodologic quality. The standard methods of the Cochrane Neonatal Review Group were used to extract data. MAIN RESULTS: Overall, the seven included trials, involving 511 infants, found no differences in time to achieve full enteral feeds between feeding methods (weighted mean difference (WMD) 2 days; 95% CI -0.3 to 3.9) . In the subgroup analysis of those studies comparing continuous nasogastric versus intermittent bolus nasogastric milk feedings the findings remained unchanged (WMD 2 days, 95% CI -0.4 to 4.1). There was no significant difference in somatic growth and incidence of NEC between feeding methods irrespective of tube placement. One study noted a trend toward more apneas during the study period in infants fed by the continuous tube feeding method compared to those fed by intermittent feedings delivered predominantly by orogastric tube placements [mean difference (MD) 14.0 apneas during study period; 95% CI -0.2 to 28.2]. In subgroup analysis based on weight groups, one study suggested that infants less than 1000 grams and 1000 to 1250 grams birth weight gained weight faster when fed by the continuous nasogastric tube feeding method compared to intermittent nasogastric tube feeding method (MD 2.0 g/day; 95% CI 0.5 to 3.5; MD 2.0 g/day; 95% CI 0.2 to 3.8, respectively). A trend toward earlier discharge for infants less than 1000 grams birth weight fed by the continuous tube feeding method compared to intermittent nasogastric tube feeding method (MD -11 days; 95% CI -21.8 to -0.2). AUTHORS' CONCLUSIONS: Small sample sizes, methodologic limitations, inconsistencies in controlling variables that may affect outcomes, and conflicting results of the studies to date make it difficult to make universal recommendations regarding the best tube feeding method for premature infants less than 1500 grams. The clinical benefits and risks of continuous versus intermittent nasogastric tube milk feeding cannot be reliably discerned from the limited information available from randomised trials to date. PMID- 22071803 TI - Operative procedures for fissure in ano. AB - BACKGROUND: Reports of direct comparisons between operative techniques for anal fissure are variable in their results. These reports are either subject to selection bias (in non-randomized studies) or observer bias (in all studies) or have inadequate numbers of patients enrolled to answer the question of efficacy. OBJECTIVES: To determine the best technique for fissure surgery. SEARCH METHODS: The Cochrane Central Register of Controlled Trials and MEDLINE (1965-2011), Medline (Pubmed) and Embase were searched March to 2011. The list of cited references in all included reports and several study authors also were helpful in finding additional comparative studies.A total of four new trials were included in this update of the review. SELECTION CRITERIA: All reports in which there was a direct comparison between at least two operative techniques were reviewed and when more than one report existed for any given pair, that report was included. All studies must also be randomised. If crude data were not presented in the report, the authors were contacted and crude data obtained. DATA COLLECTION AND ANALYSIS: The two most commonly used end points in all reported studies were treatment failure and post-operative incontinence both to flatus and faeces. These are the only two endpoints included in the meta-analysis. MAIN RESULTS: Four trials, encompassing 406 patients were included in this update, with now a total of 2056 patients in the review from 27 studies that describe and analyze 13 different operative procedures. These operative techniques used by these studies include closed lateral sphincterotomy, open lateral internal sphincterotomy, anal stretch, balloon dilation, wound closure, perineoplasty, length of sphincterotomy and fissurectomy. Two new procedures in the update, similar to anal stretch were described- sphincterolysis and controlled intermittent anal dilatation. A new comparison was described, comparing the effects of unilateral internal sphincterotomy and bilateral internal sphincterotomy.Manual Anal stretch has a higher risk of fissure persistence than internal sphincterotomy and also a significantly higher risk of minor incontinence than sphincterotomy. The combined analyses of open versus closed partial lateral internal sphincterotomy show little difference between the two procedures both in fissure persistence and risk of incontinence Unilateral internal sphincterotomy was shown to be more likely to result in treatment failure compared to bilateral internal sphincterotomy, but there is no significant difference in the risk of incontinence.Sphincterotomy was less likely to result in treatment failure when compared to fissurectomy, but there was no significant difference when considering post-operative incontinence.When comparing sphincterotomy to sphincterolysis, there was no significant difference between the two procedures both in treatment failure and risk of incontinence; the same is the case when comparing sphincterotomy with controlled anal dilation. AUTHORS' CONCLUSIONS: Manual anal stretch should probably be abandoned in the treatment of chronic anal fissure in adults. For those patients requiring surgery for anal fissure, open and closed partial lateral internal sphincterotomy appear to be equally efficacious. More data are needed to assess the effectiveness of posterior internal sphincterotomy, anterior levatorplasty, wound suture or papilla excision. Bilateral internal sphincterotomy shows promise, but needs further research into its efficacy. PMID- 22071804 TI - Medical methods for first trimester abortion. AB - BACKGROUND: Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. OBJECTIVES: To compare different medical methods for first trimester abortion. SEARCH METHODS: The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted. SELECTION CRITERIA: Types of studies Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software. MAIN RESULTS: Fifty eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups. AUTHORS' CONCLUSIONS: Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results. PMID- 22071805 TI - Opioid therapy for treating rheumatoid arthritis pain. AB - BACKGROUND: Despite improvements in the management of rheumatoid arthritis (RA), pain control is often inadequate even when inflammation is well controlled. OBJECTIVES: To assess the efficacy and safety of opioid analgesics for treating pain in patients with RA. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE for studies to May 2010. We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) abstracts and performed a handsearch of the reference lists of articles. SELECTION CRITERIA: Studies were included if they were randomized or quasi randomized controlled trials (RCTs or CCTs) which compared opioid therapy to another therapy (active or placebo) for pain in patients with RA. Outcomes of interest were pain, adverse effects, function and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, extracted the data, and performed a risk of bias assessment. MAIN RESULTS: Eleven studies (672 participants) were included in the review. Four studies assessed the efficacy of single doses of various opioid and non-opioid analgesics; a pooled analysis of these studies was not performed but in each study opioids reduced pain more than placebo. There were no differences between analgesic drugs in these studies.Seven studies were between one and six weeks in duration and assessed six different oral opioids (dextropropoxyphene, codeine, tramadol, tilidine, pentazocine, morphine), either alone or combined with non opioid analgesics. The only strong opioid investigated was controlled-release morphine sulphate, in a single study with 20 participants. Six studies compared an opioid to placebo. Opioids were superior to placebo in patient-reported global impression of change (3 studies, 324 participants: relative risk (RR) 1.44, 95% CI 1.03 to 2.03) but not for the number of withdrawals due to inadequate analgesia (4 studies, 345 participants: RR 0.82, 95% CI 0.34 to 2.0). Adverse events (most commonly nausea, vomiting, dizziness and constipation) were more frequent in patients receiving opioids compared to placebo (4 studies, 371 participants: odds ratio 3.90, 95% CI 2.31 to 6.56); the pooled risk ratio for withdrawal due to adverse events was 2.67 (3 studies, 331 participants: 95% CI 0.52 to 13.75). One study compared an opioid (codeine with paracetamol) to an NSAID (diclofenac) and found no difference in efficacy or safety between interventions. AUTHORS' CONCLUSIONS: There is limited evidence that weak oral opioids may be effective analgesics for some patients with RA, but adverse effects are common and may offset the benefits of this class of medications. There is insufficient evidence to draw conclusions regarding the use of weak opioids for longer than six weeks, or the role of strong opioids. PMID- 22071806 TI - Physical fitness training for stroke patients. AB - BACKGROUND: Levels of physical fitness are low after stroke. It is unknown whether improving physical fitness after stroke reduces disability. OBJECTIVES: To determine whether fitness training after stroke reduces death, dependence, and disability. The secondary aims were to determine the effects of training on physical fitness, mobility, physical function, quality of life, mood, and incidence of adverse events. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched April 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, July 2010), MEDLINE (1966 to March 2010), EMBASE (1980 to March 2010), CINAHL (1982 to March 2010), SPORTDiscus (1949 to March 2010), and five additional databases (March 2010). We also searched ongoing trials registers, handsearched relevant journals and conference proceedings, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing either cardiorespiratory training or resistance training, or both, with no intervention, a non-exercise intervention, or usual care in stroke survivors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality, and extracted data. We analysed data using random-effects meta-analyses. Diverse outcome measures limited the intended analyses. MAIN RESULTS: We included 32 trials, involving 1414 participants, which comprised cardiorespiratory (14 trials, 651 participants), resistance (seven trials, 246 participants), and mixed training interventions (11 trials, 517 participants). Five deaths were reported at the end of the intervention and nine at the end of follow-up. No dependence data were reported. Diverse outcome measures made data pooling difficult. The majority of the estimates of effect were not significant. Cardiorespiratory training involving walking improved maximum walking speed (mean difference (MD) 8.66 metres per minute, 95% confidence interval (CI) 2.98 to 14.34), preferred gait speed (MD 4.68 metres per minute, 95% CI 1.40 to 7.96) and walking capacity (MD 47.13 metres per six minutes, 95% CI 19.39 to 74.88) at the end of the intervention. These training effects were retained at the end of follow-up. Mixed training, involving walking, increased preferred walking speed (MD 2.93 metres per minute, 95% CI 0.02 to 5.84) and walking capacity (MD 30.59 metres per six minutes, 95% CI 8.90 to 52.28) but effects were smaller and there was heterogeneity amongst the trial results. There were insufficient data to assess the effects of resistance training. The variability in the quality of included trials hampered the reliability and generalizability of the observed results. AUTHORS' CONCLUSIONS: The effects of training on death, dependence, and disability after stroke are unclear. There is sufficient evidence to incorporate cardiorespiratory training involving walking within post-stroke rehabilitation programmes to improve speed, tolerance, and independence during walking. Further well-designed trials are needed to determine the optimal exercise prescription and identify long-term benefits. PMID- 22071807 TI - Triphasic versus monophasic oral contraceptives for contraception. AB - BACKGROUND: Side effects of oral contraceptive (OC) pills discourage adherence to and continuation of OC regimens. Strategies to decrease adverse effects led to the introduction of the triphasic OC in the 1980s. Whether triphasic OCs have higher accidental pregnancy rates than monophasic pills is unknown. Nor is it known if triphasic pills give better cycle control and fewer side effects than the monophasic pills. OBJECTIVES: To compare triphasic OCs with monophasic OCs in terms of efficacy, cycle control, and discontinuation due to side effects. SEARCH METHODS: We searched the computerized databases of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS, as well as clinical trials databases (ClinicalTrials.gov and the World Health Organization Clinical Trials Registry Platform (ICTRP)) in May 2011. Additionally, we searched the reference lists of relevant articles. We also contacted researchers and pharmaceutical companies to identify other trials not found in our search. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any triphasic OC with any monophasic pill used to prevent pregnancy. Interventions had to include at least three treatment cycles. DATA COLLECTION AND ANALYSIS: We assessed the studies found in the literature searches for possible inclusion and for their methodological quality. We contacted the authors of all included studies and of possibly randomized trials for supplemental information about the methods used and outcomes studied. We entered the data into RevMan and calculated odds ratios for the outcome measures of efficacy, breakthrough bleeding, spotting, withdrawal bleeding and discontinuation. MAIN RESULTS: Of 23 trials included, 19 examined contraceptive effectiveness. The triphasic and monophasic preparations did not differ significantly. Several trials reported favorable bleeding patterns, that is less spotting, breakthrough bleeding or amenorrhea, in triphasic versus monophasic OC users. However, meta-analysis was generally not possible due to differences in measuring and reporting the cycle disturbance data as well as differences in progestogen type and hormone dosages. No significant differences were found in the numbers of women who discontinued due to medical reasons, cycle disturbances, intermenstrual bleeding or adverse events. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine whether triphasic OCs differ from monophasic OCs in effectiveness, bleeding patterns or discontinuation rates. Therefore, we recommend monophasic pills as a first choice for women starting OC use. Large, high-quality RCTs that compare triphasic and monophasic OCs with identical progestogens are needed to determine whether triphasic pills differ from monophasic OCs. Future studies should follow the recommendations of Belsey or Mishell on recording menstrual bleeding patterns and the CONSORT reporting guidelines. PMID- 22071808 TI - Oral immunoglobulin for the prevention of rotavirus infection in low birth weight infants. AB - BACKGROUND: Rotavirus is a common neonatal nosocomial viral infection and epidemics with the newer P(6)G9 strains have been reported. Local mucosal immunity in the intestine to rotavirus is important in the resolution of infection and protection against subsequent infections. Oral administration of anti-rotaviral immunoglobulin preparations might be a useful strategy in preventing rotaviral infections, especially in low birth weight babies. OBJECTIVES: To determine the effectiveness and safety of oral immunoglobulin preparations for the prevention of rotavirus infection in hospitalized low birthweight infants (birthweight < 2500 g) SEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, CINAHL, biological Abstracts (BIOSIS), Science Citation Index for articles citing Barnes 1982 and the proceedings of the Pediatric Academic Societies from 1991 onwards were searched in July 2011. Ongoing trials were also searched at clinicaltrials.gov and controlled-trials.com SELECTION CRITERIA: The criteria used to select studies for inclusion were: 1) design: randomized or quasi randomized controlled trials; 2) participants: hospitalized low birthweight infants; 3) intervention: oral immunoglobulin preparations for prevention of rotavirus infection compared to placebo OR no intervention; 4) at least one of the following outcomes were reported: all cause mortality during hospital stay, mortality due to rotavirus infection during hospital stay, rotavirus infection , duration of diarrhea, need for rehydration, duration of viral excretion, duration of infection control measures, length of hospital stay in days, recurrent diarrhea or chronic diarrhea. DATA COLLECTION AND ANALYSIS: The two review authors independently abstracted data from the included trials. MAIN RESULTS: One published study (Barnes 1982) was eligible for inclusion in this review. Barnes 1982 found no significant difference in the rates of rotavirus infection after oral gammaglobulin versus placebo in hospitalized low birthweight babies [RR 1.27 (95% CI 0.65 to 2.37)]. In the subset of infants who became infected with rotavirus after receiving gammaglobulin or placebo for prevention of rotavirus infection, there was no significant difference in the duration of rotavirus excretion between the group who had gammaglobulin (mean 2 days, range 1 to 4 days) and the group who had placebo (mean 3 days, range 1 to 6 days). Barnes 1982 reported no adverse effects after administration of oral immunoglobulin preparations. AUTHORS' CONCLUSIONS: Current evidence does not support the use of oral immunoglobulin preparations to prevent rotavirus infection in low birthweight infants. Researchers are encouraged to conduct well-designed neonatal trials using the newer preparations of anti-rotaviral immunoglobulins (colostrum, egg yolk immunoglobulins) and include cost effectiveness evaluations. PMID- 22071809 TI - Gauze and tape and transparent polyurethane dressings for central venous catheters. AB - BACKGROUND: Central venous catheters (CVCs) facilitate venous access, allowing the intravenous administration of complex drug treatments, blood products and nutritional support, without the trauma associated with repeated venepuncture. However, CVCs are associated with a risk of infection. Some studies have indicated that the type of dressing used with them may affect the risk of infection. Gauze and tape, transparent polyurethane film dressings such as Tegaderm(r) and Opsite(r), and highly vapour-permeable transparent polyurethane film dressings such as Opsite IV3000(r), are the most common types of dressing used to secure CVCs. Currently, it is not clear which type of dressing is the most appropriate. OBJECTIVES: To compare gauze and tape with transparent polyurethane CVC dressings in terms of catheter-related infection, catheter security, tolerance to dressing material and dressing condition in hospitalised adults and children. SEARCH METHODS: For this third update, we searched The Cochrane Wounds Group Specialised Register (10 May 2011); The Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2011, Issue 2), Ovid MEDLINE (1950 to April Week 4 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, May 11, 2011); Ovid EMBASE (1980 to 2011 Week 18); and EBSCO CINAHL (1982 to 6 May 2011). SELECTION CRITERIA: All randomised controlled trials (RCTs) evaluating the effects of dressing type (e.g. gauze and tape versus transparent polyurethane dressings) on CVC-related infection, catheter security, tolerance to dressing material and dressing condition in hospitalised patients. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors for missing information. MAIN RESULTS: Six studies were included in earlier versions of the review. In this update two of the previously included papers have been excluded and two new trials have been added. Of these six trials, four compared gauze and tape with transparent polyurethane dressings (total participants = 337) and two compared different transparent polyurethane dressings (total participants = 126). Catheter related bloodstream infection was higher in the transparent polyurethane group when compared with gauze and tape; OR 4.19 (95%CI 1.02 to 17.23) however these small trials were at risk of bias so this evidence is graded low quality. There was no evidence of a difference between highly permeable polyurethane dressings and other polyurethane dressings in the prevention of catheter-related bloodstream infection (low quality evidence). No other significant differences were found. AUTHORS' CONCLUSIONS: We found a four-fold increase in the rate of catheter related blood stream infection when a polyurethane dressing was used to secure the central venous catheter however this research was at risk of bias and the confidence intervals were wide indicating high uncertainty around this estimate; so the true effect could be as small as 2% or as high as 17-fold. More, better quality research is needed regarding the relative effects of gauze and tape versus polyurethane dressings for central venous catheter sites. PMID- 22071810 TI - Non-legislative interventions for the promotion of cycle helmet wearing by children. AB - BACKGROUND: Helmets reduce bicycle-related head injuries, particularly in single vehicle crashes and those where the head strikes the ground. We aimed to identify non-legislative interventions for promoting helmet use among children, so future interventions can be designed on a firm evidence base. OBJECTIVES: To assess the effectiveness of non-legislative interventions in increasing helmet use among children; to identify possible reasons for differences in effectiveness of interventions; to evaluate effectiveness with respect to social group; to identify adverse consequences of interventions. SEARCH METHODS: We searched the following databases: Cochrane Injuries Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; PsycINFO (Ovid); PsycEXTRA (Ovid); CINAHL (EBSCO); ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED); Social Sciences Citation Index (SSCI); Conference Proceedings Citation Index-Science (CPCI-S); and PubMed from inception to April 2009; TRANSPORT to 2007; and manually searched other sources of data. SELECTION CRITERIA: We included RCTs and CBAs. Studies included participants aged 0 to 18 years, described interventions promoting helmet use not requiring enactment of legislation and reported observed helmet wearing, self reported helmet ownership or self reported helmet wearing. DATA COLLECTION AND ANALYSIS: Two independent review authors selected studies for inclusion and extracted data. We used random effects models to estimate pooled odds ratios (ORs) (with 95% confidence interval (CI)). We explored heterogeneity with subgroup analyses. MAIN RESULTS: We included 29 studies in the review, 21 of which were included in at least one meta analysis. Non-legislative interventions increased observed helmet wearing (11 studies: OR 2.08, 95% CI 1.29 to 3.34). The effect was most marked amongst community-based interventions (four studies: OR 4.30, 95% 2.24 to 8.25) and those providing free helmets (two studies: OR 4.35, 95% CI 2.13 to 8.89). Significant effects were also found amongst school-based interventions (eight studies: OR 1.73, CI 95% 1.03 to 2.91), with a smaller effect found for interventions providing education only (three studies: OR 1.43, 95% CI 1.09 to 1.88). No significant effect was found for providing subsidised helmets (seven studies: OR 2.02, 95% CI 0.98 to 4.17). Interventions provided to younger children (aged under 12) may be more effective (five studies: OR 2.50, 95% CI 1.17 to 5.37) than those provided to children of all ages (five studies: OR 1.83, 95% CI 0.98 to 3.42).Interventions were only effective in increasing self reported helmet ownership where they provided free helmets (three studies: OR 11.63, 95% CI 2.14 to 63.16).Interventions were effective in increasing self reported helmet wearing (nine studies: OR 3.27, 95% CI 1.56 to 6.87), including those undertaken in schools (six studies: OR 4.21, 95% CI 1.06 to 16.74), providing free helmets (three studies: OR 7.27, 95% CI 1.28 to 41.44), providing education only (seven studies: OR 1.93, 95% CI 1.03 to 3.63) and in healthcare settings (two studies: OR 2.78, 95% CI 1.38 to 5.61). AUTHORS' CONCLUSIONS: Non-legislative interventions appear to be effective in increasing observed helmet use, particularly community-based interventions and those providing free helmets. Those set in schools appear to be effective but possibly less so than community based interventions. Interventions providing education only are less effective than those providing free helmets. There is insufficient evidence to recommend providing subsidised helmets at present. Interventions may be more effective if provided to younger rather than older children. There is evidence that interventions offered in healthcare settings can increase self reported helmet wearing.Further high-quality studies are needed to explore whether non legislative interventions increase helmet wearing, and particularly the effect of providing subsided as opposed to free helmets, and of providing interventions in healthcare settings as opposed to in schools or communities. Alternative interventions (e.g. those including peer educators, those aimed at developing safety skills including skills in decision making and resisting peer pressure or those aimed at improving self esteem or self efficacy) need developing and testing, particularly for 11 to 18 year olds. The effect of interventions in countries with existing cycle helmet legislation and in low and middle-income countries also requires investigation. PMID- 22071811 TI - Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride. AB - BACKGROUND: In spite of more than 100 years of investigations the question of reduced sodium intake as a health prophylaxis initiative is still unsolved. OBJECTIVES: To estimate the effects of low sodium versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. SEARCH METHODS: PUBMED, EMBASE and Cochrane Central and reference lists of relevant articles were searched from 1950 to July 2011. SELECTION CRITERIA: Studies randomizing persons to low sodium and high sodium diets were included if they evaluated at least one of the above outcome parameters. DATA COLLECTION AND ANALYSIS: Two authors independently collected data, which were analysed with Review Manager 5.1. MAIN RESULTS: A total of 167 studies were included in this 2011 update.The effect of sodium reduction in normotensive Caucasians was SBP -1.27 mmHg (95% CI: -1.88, -0.66; p=0.0001), DBP -0.05 mmHg (95% CI: -0.51, 0.42; p=0.85). The effect of sodium reduction in normotensive Blacks was SBP -4.02 mmHg (95% CI:-7.37, -0.68; p=0.002), DBP -2.01 mmHg (95% CI:-4.37, 0.35; p=0.09). The effect of sodium reduction in normotensive Asians was SBP -1.27 mmHg (95% CI: -3.07, 0.54; p=0.17), DBP -1.68 mmHg (95% CI:-3.29, -0.06; p=0.04). The effect of sodium reduction in hypertensive Caucasians was SBP -5.48 mmHg (95% CI: -6.53, -4.43; p<0.00001), DBP -2.75 mmHg (95% CI: -3.34, -2.17; p<0.00001). The effect of sodium reduction in hypertensive Blacks was SBP -6.44 mmHg (95% CI:-8.85, -4.03; p=0.00001), DBP -2.40 mmHg (95% CI:-4.68, -0.12; p=0.04). The effect of sodium reduction in hypertensive Asians was SBP -10.21 mmHg (95% CI:-16.98, -3.44; p=0.003), DBP -2.60 mmHg (95% CI: -4.03, -1.16; p=0.0004).In plasma or serum there was a significant increase in renin (p<0.00001), aldosterone (p<0.00001), noradrenaline (p<0.00001), adrenaline (p<0.0002), cholesterol (p<0.001) and triglyceride (p<0.0008) with low sodium intake as compared with high sodium intake. In general the results were similar in studies with a duration of at least 2 weeks. AUTHORS' CONCLUSIONS: Sodium reduction resulted in a 1% decrease in blood pressure in normotensives, a 3.5% decrease in hypertensives, a significant increase in plasma renin, plasma aldosterone, plasma adrenaline and plasma noradrenaline, a 2.5% increase in cholesterol, and a 7% increase in triglyceride. In general, these effects were stable in studies lasting for 2 weeks or more. PMID- 22071812 TI - Preoperative hair removal to reduce surgical site infection. AB - BACKGROUND: Although preparation of people for surgery has traditionally included removal of hair from the incision site, some studies claim that preoperative hair removal is harmful, causes surgical site infections (SSIs), and should be avoided. OBJECTIVES: To determine if routine pre-operative hair removal (compared with no removal) and the timing or method of hair removal influence rates of SSI.. SEARCH METHODS: For this second update we searched the Cochrane Wounds Group Specialised Register (searched 12 August 2011); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3); Ovid MEDLINE (1950 to August Week 1 2011); Ovid MEDLINE (In-Process & Other Non Indexed Citations August 11, 2010); Ovid EMBASE (1980 to 2011 Week 31) and EBSCO CINAHL (1982 to 11August 2011). No date or language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi randomised trials (QRCTs) that compared:1) hair removal with no hair removal; 2) different methods of hair removal; 3) hair removal at different times before surgery; and, 4) hair removal in different settings (e.g. ward, anaesthetic room). DATA COLLECTION AND ANALYSIS: Three authors independently assessed relevance and quality of each trial. Data were extracted independently by two authors and cross checked. MAIN RESULTS: We included 14 trials (17 comparisons) in the review; three trials involved multiple comparisons. Six trials, two of which had three comparison arms, (972 participants) compared hair removal (shaving, clipping, or depilatory cream) with no hair removal and found no statistically significant difference in SSI rates however the comparison is underpowered. Three trials (1343 participants) that compared shaving with clipping showed significantly more SSIs associated with shaving (RR 2.09, 95% CI 1.15 to 3.80). Seven trials (1213 participants) found no significant difference in SSI rates when hair removal by shaving was compared with depilatory cream (RR 1.53, 95% CI 0.73 to 3.21), however this comparison is also underpowered. One trial compared two groups that shaved or clipped hair on the day of surgery compared with the day before surgery; there was no statistically significant difference in the number of SSIs between groups however this comparison was also underpowered.We identified no trials that compared clipping with depilatory cream; or investigated application of depilatory cream at different pre-operative time points, or hair removal in different settings (e.g. ward, anaesthetic room). AUTHORS' CONCLUSIONS: Whilst this review found no statistically significant effect on SSI rates of hair removal insufficient numbers of people have been involved in this research to allow confidence in a conclusion. When it is necessary to remove hair, the existing evidence suggests that clippers are associated with fewer SSIs than razors. There was no significant difference in SSI rates between depilatory creams and shaving, or between shaving or clipping the day before surgery or on the day of surgery however studies were small and more research is needed. PMID- 22071813 TI - Public release of performance data in changing the behaviour of healthcare consumers, professionals or organisations. AB - BACKGROUND: It is becoming increasingly common to release information about the performance of hospitals, health professionals or providers, and healthcare organisations into the public domain. However, we do not know how this information is used and to what extent such reporting leads to quality improvement by changing the behaviour of healthcare consumers, providers and purchasers, or to what extent the performance of professionals and providers can be affected. OBJECTIVES: To determine the effectiveness of the public release of performance data in changing the behaviour of healthcare consumers, professionals and organisations. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Effective Practice and Organisation of Care (EPOC) Trials Register, MEDLINE Ovid (from 1966), EMBASE Ovid (from 1979), CINAHL, PsycINFO Ovid (from 1806) and DARE up to 2011. SELECTION CRITERIA: We searched for randomised or quasi-randomised trials, interrupted time series and controlled before-after studies of the effects of publicly releasing data regarding any aspect of the performance of healthcare organisations or individuals. The papers had to report at least one main outcome related to selecting or changing care. Other outcome measures were awareness, attitude, views and knowledge of performance data and costs. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for eligibility and extracted data. For each study, we extracted data about the target groups (healthcare consumers, healthcare providers and healthcare purchasers), performance data, main outcomes (choice of healthcare provider and improvement by means of changes in care) and other outcomes (awareness, attitude, views, knowledge of performance data and costs). MAIN RESULTS: We included four studies containing more than 35,000 consumers, and 1560 hospitals. Three studies were conducted in the USA and examined consumer behaviour after the public release of performance data. Two studies found no effect of Consumer Assessment of Healthcare Providers and Systems information on health plan choice in a Medicaid population. One interrupted time series study found a small positive effect of the publishing of data on patient volumes for coronary bypass surgery and low-complication outliers for lumbar discectomy, but these effects did not persist longer than two months after each public release. No effects on patient volumes for acute myocardial infarction were found.One cluster-randomised controlled trial, conducted in Canada, studied improvement changes in care after the public release of performance data for patients with acute myocardial infarction and congestive heart failure. No effects for the composite process-of-care indicators for either condition were found, but there were some improvements in the individual process of-care indicators. There was an effect on the mortality rates for acute myocardial infarction. More quality improvement activities were initiated in response to the publicly-released report cards. No secondary outcomes were reported. AUTHORS' CONCLUSIONS: The small body of evidence available provides no consistent evidence that the public release of performance data changes consumer behaviour or improves care. Evidence that the public release of performance data may have an impact on the behaviour of healthcare professionals or organisations is lacking. PMID- 22071814 TI - Probiotics for the prevention of pediatric antibiotic-associated diarrhea. AB - BACKGROUND: Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population. OBJECTIVES: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. SEARCH METHODS: MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and the Web of Science (inception to May 2010) were searched along with specialized registers including the Cochrane IBD/FBD review group, CISCOM (Centralized Information Service for Complementary Medicine), NHS Evidence, the International Bibliographic Information on Dietary Supplements as well as trial registries. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were also searched. SELECTION CRITERIA: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. DATA COLLECTION AND ANALYSIS: Study selection, data extraction as well as methodological quality assessment using the risk of bias instrument was conducted independently and in duplicate by two authors. Dichotomous data (incidence of diarrhea, adverse events) were combined using a pooled relative risk and risk difference (adverse events), and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. For overall pooled results on the incidence of diarrhea, sensitivity analyses included available case versus extreme-plausible analyses and random- versus fixed-effect models. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, antibiotic agent as well as risk of bias. MAIN RESULTS: Sixteen studies (3432 participants) met the inclusion criteria. Trials included treatment with either Bacillus spp., Bifidobacterium spp., Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., or Streptococcus spp., alone or in combination. Nine studies used a single strain probiotic agent, four combined two probiotic strains, one combined three probiotic strains, one product included ten probiotic agents, and one study included two probiotic arms that used three and two strains respectively. The risk of bias was determined to be high in 8 studies and low in 8 studies. Available case (patients who did not complete the studies were not included in the analysis) results from 15/16 trials reporting on the incidence of diarrhea show a large, precise benefit from probiotics compared to active, placebo or no treatment control. The incidence of AAD in the probiotic group was 9% compared to 18% in the control group (2874 participants; RR 0.52; 95% CI 0.38 to 0.72; I(2) = 56%). This benefit was not statistically significant in an extreme plausible (60% of children loss to follow-up in probiotic group and 20% loss to follow-up in the control group had diarrhea) intention to treat (ITT) sensitivity analysis. The incidence of AAD in the probiotic group was 16% compared to 18% in the control group (3392 participants; RR 0.81; 95% CI 0.63 to 1.04; I(2) = 59%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (>=5 billion CFUs/day) is more effective than low probiotic dose (< 5 billion CFUs/day), interaction P value = 0.010. For the high dose studies the incidence of AAD in the probiotic group was 8% compared to 22% in the control group (1474 participants; RR 0.40; 95% CI 0.29 to 0.55). For the low dose studies the incidence of AAD in the probiotic group was 8% compared to 11% in the control group (1382 participants; RR 0.80; 95% CI 0.53 to 1.21). An extreme plausible ITT subgroup analysis was marginally significant for high dose probiotics. For the high dose studies the incidence of AAD in the probiotic group was 17% compared to 22% in the control group (1776 participants; RR 0.72; 95% CI 0.53 to 0.99; I(2) = 58%). None of the 11 trials (n = 1583) that reported on adverse events documented any serious adverse events. Meta-analysis excluded all but an extremely small non-significant difference in adverse events between treatment and control (RD 0.00; 95% CI -0.01 to 0.02). AUTHORS' CONCLUSIONS: Despite heterogeneity in probiotic strain, dose, and duration, as well as in study quality, the overall evidence suggests a protective effect of probiotics in preventing AAD. Using 11 criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate that the subgroup effect based on dose (>=5 billion CFU/day) was credible. Based on high-dose probiotics, the number needed to treat (NNT) to prevent one case of diarrhea is seven (NNT 7; 95% CI 6 to 10). However, a GRADE analysis indicated that the overall quality of the evidence for the primary endpoint (incidence of diarrhea) was low due to issues with risk of bias (due to high loss to follow-up) and imprecision (sparse data, 225 events). The benefit for high dose probiotics (Lactobacillus rhamnosus or Saccharomyces boulardii) needs to be confirmed by a large well-designed randomized trial. More refined trials are also needed that test strain specific probiotics and evaluate the efficacy (e.g. incidence and duration of diarrhea) and safety of probiotics with limited losses to follow-up. It is premature to draw conclusions about the efficacy and safety of other probiotic agents for pediatric AAD. Future trials would benefit from a standard and valid outcomes to measure AAD. PMID- 22071815 TI - Risk scoring systems for predicting preterm birth with the aim of reducing associated adverse outcomes. AB - BACKGROUND: Identification of pregnancies that are higher risk than average is important to allow the possibility of interventions aimed at preventing adverse outcomes like preterm birth. Many scoring systems designed to classify the risk of a number of poor pregnancy outcomes (e.g. perinatal mortality, low birthweight, and preterm birth) have been developed, but they have usually been introduced without evaluation of their utility and validity. OBJECTIVES: To determine whether the use of a risk-screening tool designed to predict preterm birth (in combination with appropriate consequent interventions) reduces the incidence of preterm birth and very preterm birth, and associated adverse outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2010), CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE (1966 to 17 December 2010), EMBASE (1974 to 17 December 2010), and CINAHL (1982 to 17 December 2010). SELECTION CRITERIA: All randomised or quasi-randomised (including cluster-randomised) or controlled clinical trials that compared the incidence of preterm birth between groups that used a risk scoring instrument to predict preterm birth with those who used an alternative instrument, or no instrument; or that compared the use of the same instrument at different gestations. The reports may have been published in peer reviewed or non peer reviewed publications, or not published, and written in any language. DATA COLLECTION AND ANALYSIS: All review authors planned to independently assess for inclusion all the potential studies we identified as a result of the search strategy. However, we identified no eligible studies. MAIN RESULTS: Extensive searching revealed no trials of the use of risk scoring systems to prevent preterm birth. AUTHORS' CONCLUSIONS: The role of risk scoring systems in the prevention of preterm birth is unknown.There is a need for prospective studies that evaluate the use of a risk-screening tool designed to predict preterm birth (in combination with appropriate consequent interventions) to prevent preterm birth, including qualitative and/or quantitative evaluation of their impact on women's well-being. If these prove promising, they should be followed by an adequately powered, well-designed randomised controlled trial. PMID- 22071816 TI - Hydralazine for essential hypertension. AB - BACKGROUND: Hypertension is associated with an increased risk of stroke, myocardial infarction and congestive heart failure. Hydralazine is a direct acting vasodilator which has been used for the treatment of hypertension since the 1950's. Although it has largely been replaced by newer antihypertensive drugs with more acceptable tolerability profiles, hydralazine is still widely used in developing countries due to its lower cost. A review of its relative effectiveness compared to placebo on surrogate and clinical outcomes is justified. OBJECTIVES: To quantify the effect of hydralazine compared to placebo in randomized controlled trials (RCTs) on all cause mortality, cardiovascular mortality, serious adverse events, myocardial infarctions, strokes, withdrawals due to adverse effects and blood pressure in patients with primary hypertension. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials (2011, Issue 3), MEDLINE (1948-August 2011), International Pharmaceutical Abstracts (1970-June 2009) and EMBASE (1980-August 2011). Bibliographic citations from retrieved studies were also reviewed. No language restrictions were applied. SELECTION CRITERIA: We selected RCTs studying the effect of oral hydralazine compared to oral placebo in patients with primary hypertension. We excluded studies of patients with secondary hypertension or gestational hypertension. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality using the risk of bias tool. Data synthesis and analysis was performed using RevMan 5. MAIN RESULTS: The search strategy did not yield any randomized controlled trials comparing hydralazine to placebo for inclusion in this review. There is insufficient evidence to conclude on the effects of hydralazine versus placebo on mortality, morbidity, withdrawals due to adverse effects, serious adverse events, or systolic and diastolic blood pressure. Some of the adverse effects related to hydralazine that have been reported in the literature include reflex tachycardia, hemolytic anemia, vasculitis, glomerulonephritis, and a lupus-like syndrome. AUTHORS' CONCLUSIONS: Hydralazine may reduce blood pressure when compared to placebo in patients with primary hypertension, however this data is based on before and after studies, not RCTs. Furthermore, its effect on clinical outcomes remains uncertain. PMID- 22071817 TI - Exercise for improving balance in older people. AB - BACKGROUND: In older adults, diminished balance is associated with reduced physical functioning and an increased risk of falling. This is an update of a Cochrane review first published in 2007. OBJECTIVES: To examine the effects of exercise interventions on balance in older people, aged 60 and over, living in the community or in institutional care. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE and EMBASE (to February 2011). SELECTION CRITERIA: Randomised controlled studies testing the effects of exercise interventions on balance in older people. The primary outcomes of the review were clinical measures of balance. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently assessed risk of bias and extracted data from studies. Data were pooled where appropriate. MAIN RESULTS: This update included 94 studies (62 new) with 9,917 participants. Most participants were women living in their own home.Most trials were judged at unclear risk of selection bias, generally reflecting inadequate reporting of the randomisation methods, but at high risk of performance bias relating to lack of participant blinding, which is largely unavoidable for these trials. Most studies only reported outcome up to the end of the exercise programme.There were eight categories of exercise programmes. These are listed below together with primary measures of balance for which there was some evidence of a statistically significant effect at the end of the exercise programme. Some trials tested more than one type of exercise. Crucially, the evidence for each outcome was generally from only a few of the trials for each exercise category. 1. Gait, balance, co-ordination and functional tasks (19 studies of which 10 provided primary outcome data): Timed Up & Go test (mean difference (MD) -0.82 s; 95% CI -1.56 to -0.08 s, 114 participants, 4 studies); walking speed (standardised mean difference (SMD) 0.43; 95% CI 0.11 to 0.75, 156 participants, 4 studies), and the Berg Balance Scale (MD 3.48 points; 95% CI 2.01 to 4.95 points, 145 participants, 4 studies).2. Strengthening exercise (including resistance or power training) (21 studies of which 11 provided primary outcome data): Timed Up & Go Test (MD -4.30 s; 95% CI -7.60 to -1.00 s, 71 participants, 3 studies); standing on one leg for as long as possible with eyes closed (MD 1.64 s; 95% CI 0.97 to 2.31 s, 120 participants, 3 studies); and walking speed (SMD 0.25; 95% CI 0.05 to 0.46, 375 participants, 8 studies).3. 3D (3 dimensional) exercise (including Tai Chi, qi gong, dance, yoga) (15 studies of which seven provided primary outcome data): Timed Up & Go Test (MD -1.30 s; 95% CI -2.40 to 0.20 s, 44 participants, 1 study); standing on one leg for as long as possible with eyes open (MD 9.60 s; 95% CI 6.64 to 12.56 s, 47 participants, 1 study), and with eyes closed (MD 2.21 s; 95% CI 0.69 to 3.73 s, 48 participants, 1 study); and the Berg Balance Scale (MD 1.06 points; 95% CI 0.37 to 1.76 points, 150 participants, 2 studies).4. General physical activity (walking) (seven studies of which five provided primary outcome data). 5. General physical activity (cycling) (one study which provided data for walking speed). 6. Computerised balance training using visual feedback (two studies, neither of which provided primary outcome data). 7. Vibration platform used as intervention (three studies of which one provided primary outcome data).8. Multiple exercise types (combinations of the above) (43 studies of which 29 provided data for one or more primary outcomes): Timed Up & Go Test (MD -1.63 s; 95% CI -2.28 to -0.98 s, 635 participants, 12 studies); standing on one leg for as long as possible with eyes open (MD 5.03 s; 95% CI 1.19 to 8.87 s, 545 participants, 9 studies), and with eyes closed ((MD 1.60 s; 95% CI -0.01 to 3.20 s, 176 participants, 2 studies); walking speed (SMD 0.04; 95% CI -0.10 to 0.17, 818 participants, 15 studies); and the Berg Balance Scale ((MD 1.84 points; 95% CI 0.71 to 2.97 points, 80 participants, 2 studies).Few adverse events were reported but most studies did not monitor or report adverse events.In general, the more effective programmes ran three times a week for three months and involved dynamic exercise in standing. AUTHORS' CONCLUSIONS: There is weak evidence that some types of exercise (gait, balance, co-ordination and functional tasks; strengthening exercise; 3D exercise and multiple exercise types) are moderately effective, immediately post intervention, in improving clinical balance outcomes in older people. Such interventions are probably safe. There is either no or insufficient evidence to draw any conclusions for general physical activity (walking or cycling) and exercise involving computerised balance programmes or vibration plates. Further high methodological quality research using core outcome measures and adequate surveillance is required. PMID- 22071818 TI - One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. AB - BACKGROUND: Animal studies and trials in older children and adults suggest that a one dose per day regimen of gentamicin is superior to a multiple doses per day regimen. OBJECTIVES: To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. SEARCH METHODS: Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, April 2011), MEDLINE (1966 to April 2011), EMBASE 1980 to April 2011, and CINAHL (December 1982 to April 2011). Abstracts of the Society for Pediatric Research were searched from 1980 to 2010 inclusive. SELECTION CRITERIA: All randomised or quasi randomised controlled trials comparing one dose per day ( 'once a day') compared to multiple doses per day ( 'multiple doses a day') of gentamicin to newborn infants < 28 days of life. DATA COLLECTION AND ANALYSIS: Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Eleven studies were included (N = 574) and nineteen excluded. All infants in both 'once a day' as well as 'multiple doses a day' regimen showed adequate clearance of sepsis [typical RD 0.00 (95% CI - 0.19 to 0.19); 3 trials; N = 36]. For the other primary outcome measures relating to gentamicin pharmacokinetics 'once a day' dosing of gentamicin was superior. 'Once a day' gentamicin regimen was associated with less failures to attain peak level of at least 5 ug/ml [typical RR 0.22 (95% CI 0.11 to 0.47); 9 trials; N = 422] and less failures to achieve trough levels of < 2 ug/ml [typical RR 0.38 (95% CI 0.27 to 0.55); 11 trials N = 503] compared to 'multiple doses a day' regimen.Ototoxicity and nephrotoxicity were not noted with either of the treatment regimens. AUTHORS' CONCLUSIONS: There is insufficient evidence from the currently available RCTs to conclude whether 'once a day' or 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggests that pharmacokinetic properties of 'once a day' gentamicin regimen are superior to 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There is no change in nephrotoxicity or auditory toxicity. Based on this assessment of pharmacokinetics, 'once a day regimen' may be superior in treating neonatal sepsis in neonates greater than 32 weeks gestation. PMID- 22071819 TI - Creatine and creatine analogues in hypertension and cardiovascular disease. AB - BACKGROUND: The creatine kinase system, the central regulatory system of cellular energy metabolism, provides ATP in situ at ATP-ases involved in ion transport and muscle contraction. Furthermore, the enzyme system provides relative protection from tissue ischaemia and acidosis. The system could therefore be a target for pharmacologic intervention. OBJECTIVES: To systematically evaluate evidence regarding the effectiveness of interventions directly targeting the creatine kinase system as compared to placebo control in adult patients with essential hypertension or cardiovascular disease. SEARCH METHODS: Electronic databases searched: Medline (1950 - Feb 2011), Embase (up to Feb 2011), the Cochrane Controlled Trials Register (issue 3, Aug 2009), Latin-American/Caribbean databank Lilacs; references from textbooks and reviews; contact with experts and pharmaceutical companies; and searching the Internet. There was no language restriction. SELECTION CRITERIA: Randomized controlled trials comparing creatine, creatine phosphate, or cyclocreatine (any route, dose or duration of treatment) with placebo; in adult patients with essential hypertension, heart failure, or myocardial infarction. We did not include papers on the short-term use of creatine during cardiac surgery. DATA COLLECTION AND ANALYSIS: The outcomes assessed were death, total myocardial infarction (fatal or non-fatal), hospitalizations for congestive heart failure, change in ejection fraction, and changes in diastolic and systolic blood pressure in mm Hg or as percent change. MAIN RESULTS: Full reports or abstracts from 1164 papers were reviewed, yielding 11 trials considering treatment with creatine or creatine analogues in 1474 patients with heart failure, ischemic heart disease or myocardial infarction. No trial in patients with hypertension was identified. Eleven trials (1474 patients, 35 years or older) comparing add-on therapy of the creatine-based drug on standard treatment to placebo control in patients with heart failure (6 trials in 1226 / 1474 patients ), or acute myocardial infarction (4 trials in 220 / 1474 patients) or 1 in ischemic heart disease (28 / 1474 patients) were identified. The drugs used were either creatine, creatine phosphate (orally, intravenously, or intramuscular) or phosphocreatinine. In the trials considering heart failure all three different compounds were studied; creatine orally (Gordon 1995, Kuethe 2006), creatine phosphate via intravenous infusion (Ferraro 1996, Grazioli 1992), and phosphocreatinine orally (Carmenini 1994, Maggi 1990). In contrast, the acute myocardial infarction trials studied intravenous creatine phosphate only. In the ischemic heart disease trial (Pedone 1984) creatine phosphate was given twice daily through an intramuscular injection to outpatients and through an intravenous infusion to inpatients. The duration of the study intervention was shorter for the acute patients, from a two hour intravenous infusion of creatine phosphate in acute myocardial infarction (Ruda 1988, Samarenko 1987), to six months in patients with heart failure on oral phosphocreatinine therapy (Carmenini 1994). In the acute myocardial infarction patients the follow-up period varied from the acute treatment period (Ruda 1988) to 28 days after start of the symptoms (Samarenko 1987) or end of the hospitalization period (Zochowski 1994). In the other trials there was no follow-up after discontinuation of treatment, except for Gordon 1995 which followed the patients until four days after stopping the intervention.Only two out of four trials in patients with acute myocardial infarction reported mortality outcomes, with no significant effect of creatine or creatine analogues (RR 0.73, CI: 0.22 - 2.45). In addition, there was no significance on the progression of myocardial infarction or improvement on ejection fraction. The main effect of the interventions seems to be on improvement of dysrhythmia. AUTHORS' CONCLUSIONS: This review found inconclusive evidence to decide on the use of creatine analogues in clinical practice. In particular, it is not clear whether there is an effect on mortality, progression of myocardial infarction and ejection fraction, while there is some evidence that dysrhythmia and dyspnoea might improve. However, it is not clear which analogue, dose, route of administration, and duration of therapy is most effective. Moreover, given the small sample size of the discussed trials and the heterogeneity of the population included in these reports, larger clinical studies are needed to confirm these observations. PMID- 22071820 TI - Ultrasound use for the placement of haemodialysis catheters. AB - BACKGROUND: A significant proportion of patients starting dialysis do so with a temporary or tunnelled haemodialysis catheter. Insertion of these catheters can be achieved either by using the anatomical landmarks for the veins into which they are inserted or using ultrasound guidance. It has been suggested that the use of ultrasound guidance reduces the immediate complications of haemodialysis catheter insertions such as pneumothorax or arterial puncture. OBJECTIVES: The aim of the review was to compare the use of real-time 2-dimensional (2-D) Doppler ultrasound venous imaging in the insertion of percutaneous central venous catheters for dialysis versus the traditional "blind" landmark method. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL). Reference lists of identified studies and relevant narrative reviews were also screened. Search date: January 2011. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs evaluating ultrasound guidance in the percutaneous insertion of central venous catheters for dialysis (both cuffed and uncuffed) against the traditional blind landmark method. DATA COLLECTION AND ANALYSIS: Two authors assessed risk of bias and extracted data. Statistical analyses were performed using the random effects model and the results expressed as risk ratios (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: We identified seven studies enrolling 767 patients and with 830 catheter insertions. Three of seven studies described the method of random sequence generation, none described allocation concealment, and blinding of participants and personnel was not possible. Real-time ultrasound guidance was found to significantly reduce the risk of catheter placement failure on the first attempt (5 studies, 595 catheters): RR 0.40, 95% CI 0.30 to 0.52), significantly reduce the risk of arterial puncture (6 studies, 535 catheters: RR 0.13, 95% CI 0.04 to 0.37) and haematomas (4 studies, 323 catheters: RR 0.22, 95% CI 0.06 to 0.81) when compared to the landmark method. The time taken for successful cannulation was significantly lower with the use of real-time ultrasound guidance (1 study, 73 catheters: MD -1.40 min, 95% CI -2.17 to -0.63) and there were less attempts/catheter insertion (1 study, 110 catheters: -0.35, 95% CI -0.54 to -0.16). AUTHORS' CONCLUSIONS: Use of real-time 2-D Doppler ultrasound guidance has significant benefits with respect to the number if catheters successfully inserted on the first attempt, reduction in the risk of arterial puncture and haematomas and the time taken for successful vein puncture. PMID- 22071821 TI - Cognitive reframing for carers of people with dementia. AB - BACKGROUND: The balance of evidence about whether psychosocial interventions for caregivers of people with dementia could reduce carers' psychological morbidity and delay their relatives' institutionalisation is now widely regarded as moderately positive (Brodaty 2003; Spijker 2008). Multi-component, tailor-made psychosocial interventions are considered to be particularly promising (Brodaty 2003; Spijker 2008). These interventions involve multiple mechanisms of action. In this review we focused solely on the effectiveness of one element within psychosocial interventions, cognitive reframing. Cognitive reframing is a component of cognitive behavioral therapy (CBT). In dementia care, cognitive reframing interventions focus on family carers' maladaptive, self-defeating or distressing cognitions about their relatives' behaviors and about their own performance in the caring role. OBJECTIVES: The objective of this review was to evaluate the effectiveness of cognitive reframing interventions for family carers of people with dementia on their psychological morbidity and stress. SEARCH METHODS: The trials were identified by searching (5 April 2009) the Cochrane Dementia and Cognitive Improvement Group Specialized Register, which contains records from major healthcare databases: The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, ongoing trial databases and grey literature sources. For more detailed information on what the Group's specialized register contains and to view the search strategies see the Cochrane Dementia and Cognitive Improvement Group methods used in reviews.The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS and a number of trial registers and grey literature sources were also searched separately on 5 April 2009. SELECTION CRITERIA: Randomised controlled trials of cognitive reframing interventions for family carers of people with dementia. DATA COLLECTION AND ANALYSIS: Three assessors (MVD, ID, JmC) independently judged whether the intervention being studied was documented in a trial; two assessors assessed trial quality. MAIN RESULTS: Pooled data indicated a beneficial effect of cognitive reframing interventions on carers' psychological morbidity, specifically anxiety (standardised mean difference (SMD) -0.21; 95% confidence interval (CI) -0.39 to -0.04), depression (SMD -0.66; 95% CI -1.27 to -0.05), and subjective stress (SMD -0.23; 95% CI 0.43 to -0.04). No effects were found for carers' coping, appraisal of the burden, reactions to their relatives' behaviors, or institutionalization of the person with dementia. AUTHORS' CONCLUSIONS: Cognitive reframing for family carers of people with dementia seems to reduce psychological morbidity and subjective stress but without altering appraisals of coping or burden. The results suggest that it may be an effective component of individualised, multi-component interventions for carers. Identifying studies with relevant interventions was a challenge for this review. The impact of cognitive reframing might be higher when used alongside other interventions because this offers better opportunities to tailor cognitive reframing to actual everyday carer problems. PMID- 22071822 TI - Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. AB - BACKGROUND: Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy. OBJECTIVES: To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer. SEARCH METHODS: We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010 and May 2011. In addition, we handsearched and cascade searched the major gynaecological oncology journals. SELECTION CRITERIA: The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration. DATA COLLECTION AND ANALYSIS: We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software. MAIN RESULTS: Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route. AUTHORS' CONCLUSIONS: Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials. PMID- 22071823 TI - Interventions to reduce haemorrhage during myomectomy for fibroids. AB - BACKGROUND: Uterine myomas (fibroids) are benign tumours of the uterus. Myomectomy, the surgical removal of myomas, can be associated with life threatening bleeding and prolonged postoperative stay. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. This is an update of the review published in The Cochrane Library Issue 3, 2009. OBJECTIVES: To assess the effectiveness, safety, tolerability, and costs of interventions to reduce blood loss during myomectomy. SEARCH STRATEGY: Electronic searches were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (1950 to February 2011), EMBASE (1980 to February 2011), CINAHL (1982 to February 2011), and PsycINFO (1801 to February 2011). SELECTION CRITERIA: Only randomised controlled trials (RCTs) that compared the use of interventions to reduce blood loss during myomectomy to placebo or no treatment were included. DATA COLLECTION AND ANALYSIS: The two authors independently selected RCTs for inclusion, assessed the methodological quality of trials, and extracted data. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). MAIN RESULTS: Twelve RCTs with 674 participants met our inclusion criteria. The interventions were intramyometrial vasopressin (two RCTs), intravenous oxytocin (two RCTs), peri-cervical tourniquet (two RCTs), and one RCT each for vaginal misoprostol, gelatin thrombin matrix, chemical dissection with sodium-2-mercaptoethane sulfonate (mesna), intramyometrial bupivacaine plus epinephrine, tranexamic acid, and myoma enucleation by morcellation. We found significant reductions in blood loss with misoprostol (MD -149.00 ml, 95% CI 229.24 to -68.76), vasopressin (MD -298.72 ml, 95% CI -593.10 to -4.34; I(2) = 99%), bupivacaine plus epinephrine (MD -68.60 ml, 95% CI -93.69 to - 43.51), tranexamic acid (MD -243 ml, 95% CI -460 to -25.98), peri-cervical tourniquet (MD -289.44, 95% CI -406.55 to -172.32; I(2) = 95%), and gelatin-thrombin matrix (MD 545.00 ml, 95% CI -593.26 to -496.74). There was no evidence of an effect on blood loss with oxytocin or morcellation. None of the interventions significantly increased myomectomy-related complications. The trials did not assess the costs of the different interventions. AUTHORS' CONCLUSIONS: There is limited evidence that misoprostol, vasopressin, bupivacaine plus epinephrine, tranexamic acid, gelatin thrombin matrix, peri-cervical tourniquet, and mesna may reduce bleeding during myomectomy. Bupivacaine plus epinephrine has limited clinical importance compared with other interventions as the clinical impact was small. There is no evidence that oxytocin and morcellation reduce blood loss. Further well designed studies are required to establish effectiveness, safety and the costs of different interventions for reducing blood loss during myomectomy. PMID- 22071824 TI - Laetrile treatment for cancer. AB - BACKGROUND: Laetrile is the name for a semi-synthetic compound which is chemically related to amygdalin, a cyanogenic glycoside from the kernels of apricots and various other species of the genus Prunus. Laetrile and amygdalin are promoted under various names for the treatment of cancer although there is no evidence for its efficacy. Due to possible cyanide poisoning, laetrile can be dangerous. OBJECTIVES: To assess the alleged anti-cancer effect and possible adverse effects of laetrile and amygdalin. SEARCH METHODS: We searched the following databases: CENTRAL (2011, Issue 1); MEDLINE (1951-2011); EMBASE (1980 2011); AMED; Scirus; CancerLit; CINAHL (all from 1982-2011); CAMbase (from 1998 2011); the MetaRegister; the National Research Register; and our own files. We examined reference lists of included studies and review articles and we contacted experts in the field for knowledge of additional studies. We did not impose any restrictions of timer or language. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs. DATA COLLECTION AND ANALYSIS: We searched eight databases and two registers for studies testing laetrile or amygdalin for the treatment of cancer. Two review authors screened and assessed articles for inclusion criteria. MAIN RESULTS: We located over 200 references, 63 were evaluated in the original review and an additional 6 in this update. However, we did not identify any studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: The claims that laetrile or amygdalin have beneficial effects for cancer patients are not currently supported by sound clinical data. There is a considerable risk of serious adverse effects from cyanide poisoning after laetrile or amygdalin, especially after oral ingestion. The risk-benefit balance of laetrile or amygdalin as a treatment for cancer is therefore unambiguously negative. PMID- 22071825 TI - Chinese medicinal herbs for measles. AB - BACKGROUND: Measles is an infectious disease caused by the Morbillivirus. Chinese physicians believe that medicinal herbs are effective in alleviating symptoms and preventing complications. Chinese herbal medicines are dispensed according to the particular symptoms. This is the second update of a Cochrane Review first published in 2006. OBJECTIVES: To assess the effectiveness and possible adverse effects of Chinese medicinal herbs for measles. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Clinical Trials (CENTRAL Issue 1, 2011) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to March week 5, 2011), EMBASE (1980 to April 2011), Web of Science (2005 to 30 April 2011), AMED (1985 to 30 April 2011), Chinese Biomedical Database (1976 to 30 June 2011), VIP Information (1989 to 30 June 2011), China National Knowledge Infrastructure (CNKI) (1976 to 30 June 2011), Chinese Journals full-article database (1994 to 30 June 2011) and the metaRegister of Controlled Trials for ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of Chinese medicinal herbs in patients with measles (without complications). DATA COLLECTION AND ANALYSIS: Two review authors (SC, TW) independently assessed trial quality and extracted data. We telephone interviewed the trial authors for missing information regarding participant allocation. Some trials allocated participants according to the sequence they were admitted to the trials, that is to say, by using a pseudo-random allocation method. None of the trials concealed the allocation or used blinding methods. MAIN RESULTS: We did not identify any suitable trials for inclusion. In this updated review we identified 80 trials which claimed to use random allocation. We contacted 32 trial authors by telephone and learned that the allocation methods used were not randomised. We excluded 34 studies because the participants experienced complications such as pneumonia. We excluded 10 trials because of non random allocation and complications experienced by the participants. We were unable to contact the remaining four trials' authors, so they require further assessment and have been allocated to the 'Studies awaiting classification' section. AUTHORS' CONCLUSIONS: There is no RCT evidence for or against Chinese medicinal herbs as a treatment for measles. We hope high-quality, robust RCTs in this field will be conducted in the future. PMID- 22071826 TI - Prostaglandins for adult liver transplanted patients. AB - BACKGROUND: Prostaglandins may reduce ischaemic injury after liver transplantation. Several small randomised trials have evaluated the effects of prostaglandins in patients undergoing liver transplantation. Results of these trials are inconsistent, and none has enough power to reliably exclude effects of prostaglandins. OBJECTIVES: To assess the benefits and harms of prostaglandin E1 or E2 in adult liver-transplanted patients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS (search on 20 April 2011). In addition, we perused the reference lists of the identified studies and contacted trials investigators, and national and international experts in order to identify more trials for the review. SELECTION CRITERIA: We included randomised clinical trials evaluating prostaglandin E1 or E2 initiated in the perioperative period versus placebo or standard treatment for adult patients undergoing liver transplantation. We did not apply any language or publication status restrictions. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated methodological quality, ie, risk of bias of the included trials, and extracted data using standardised data extraction forms. We contacted trial investigators in attempt to retrieve information not available in the original manuscripts. We used random-effects model meta-analyses and fixed-effect model meta-analyses to estimate the odds ratio with 95% confidence interval (CI). MAIN RESULTS: We included ten trials in which 652 patients were randomised. The risk of bias was considered high in most trials. There was no significant effect of prostaglandins on all-cause mortality (37/298[12.4%] in prostaglandin group versus 47/312[15.1%] in control group; OR 0.84, 95% CI 0.53 to 1.37; I(2) = 0%), on primary non function of the allograft (8/238 [3.4%] versus. 16/250[6.4%] ;OR 0.55, 95% CI 0.23 to 1.33; I(2) = 0%), and on liver re-transplantation (12/161[7.5%] versus 14/171[8.2%]; OR 0.99, 95% CI 0.44 to 2.25; I(2) = 0%). Prostaglandins seemed to significantly decrease the risk of acute kidney failure requiring dialysis (13/158[8.2%] versus 34/171[9.9%]; OR 0.37, 95% CI 0.18 to 0.75; I(2) = 0%). There was no significant increase in the risk of adverse events with prostaglandins. AUTHORS' CONCLUSIONS: We found no evidence that the administration of prostaglandins to liver transplanted patients reduces the risk of death, primary non-function of the allograft, or liver re-transplantation. Prostaglandins might reduce the risk of acute kidney failure requiring dialysis, but the quality of the evidence is considered only moderate due to high risk of bias in most of the included trials. Moreover, there are risks of outcome measure reporting bias and random errors. Therefore, further randomised, placebo controlled trials are deemed necessary. PMID- 22071827 TI - Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units. AB - BACKGROUND: Candida is a common nosocomial infection and is associated with increased healthcare costs. In neonates, candida infection is associated with high mortality and morbidity and is transmitted by direct and indirect contact. Patient isolation measures, i.e. single room isolation or cohorting, are usually recommended for infections that spread by contact. OBJECTIVES: To determine the effect of patient isolation measures (single room isolation and/or cohorting) for infants with candida colonization or infection as an adjunct to routine infection control measures on the transmission of candida to other infants in the neonatal unit. SEARCH METHODS: Relevant trials in any language were searched in the following databases in July 2011: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011), MEDLINE, BIOSIS, EMBASE and CINAHL. Proceedings of the Pediatric Academic Societies (from 1987) and ongoing trials were searched. SELECTION CRITERIA: Types of studies: Cluster randomized trials (where clusters may be defined by hospital, ward, or other subunits of the hospital). TYPES OF PARTICIPANTS: Neonatal units caring for infants colonized or infected with Candida. Types of interventions: A policy of patient isolation measures (single room isolation or cohorting of infants with Candida colonization or infection) compared to routine isolation measures. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group (CNRG) were used to identify studies and to assess the methodological quality of eligible cluster-randomized trials. Infection rates and colonization rates were to be expressed as rate ratios for each trial and if appropriate for meta-analysis, the generic inverse variance method in RevMan was to be used. MAIN RESULTS: No eligible trials were identified. AUTHORS' CONCLUSIONS: The review found no evidence to either support or refute the use of patient isolation measures (single room isolation or cohorting) in neonates with candida colonization or infection.Despite the evidence for transmission of candida by contact and evidence of cross-infection by health care workers, no standard policy of patient isolation measures beyond routine infection control measures exists in the neonatal unit. There is an urgent need to research the role of patient isolation measures for preventing transmission of candida in the neonatal unit. Well designed trials randomizing clusters of units or hospitals to a type of patient isolation method intervention are needed. PMID- 22071828 TI - Nutritional supplements for people being treated for active tuberculosis. AB - BACKGROUND: Tuberculosis and malnutrition are linked in a complex relationship. The infection may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there are no evidence-based nutritional guidance for adults and children being treated for tuberculosis. OBJECTIVES: To assess the effects of oral nutritional supplements (food, protein/energy supplements or micronutrients) on tuberculosis treatment outcomes and recovery in people on antituberculous drug therapy for active tuberculosis. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, mRCT, and the Indian Journal of Tuberculosis to July 2011, and checked the reference lists of all included studies. SELECTION CRITERIA: Randomized controlled trials comparing any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed the risk of bias. Results are presented as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CI). Where appropriate, data from trials with similar interventions and outcomes have been pooled. The quality of evidence was assessed using the GRADE methods. MAIN RESULTS: Twenty-three trials, with 6842 participants, were included. Macronutrient supplementation Five trials assessed the provision of free food, or high energy supplements, although none were shown to provide a total daily kilocalorie intake above the current daily recommended intake for the non infected population.The available trials were too small to reliably prove or exclude clinically important benefits on mortality, cure, or treatment completion. One small trial from India did find a statistically significant benefit on treatment completion, and clearance of the bacteria from the sputum, but these findings have not been confirmed in larger trials elsewhere (VERY LOW quality evidence).The provision of free food or high-energy nutritional products probably does produce a modest increase in weight gain during treatment for active tuberculosis (MODERATE quality evidence). Two small studies provide some evidence that physical function and quality of life may also be improved but the trials were too small to have much confidence in the result (LOW quality evidence). These effects were not seen in the one trial which included only human immunodeficiency virus (HIV)-positive patients.Micronutrient supplementation Five trials assessed multi-micronutrient supplementation in doses up to ten times the dietary reference intake, and 12 trials assessed single or dual micronutrient supplementation.There is insufficient evidence to judge whether multi micronutrients have a beneficial effect on mortality in HIV- negative patients with tuberculosis (VERY LOW quality evidence), but the available studies show that multi-micronutrients probably have little or no effect on mortality in HIV positive patients with tuberculosis (MODERATE quality evidence). No studies have assessed the effects of multi-micronutrients on cure, or treatment completion.Multi-micronutrient supplements may have little or no effect on the proportion of tuberculosis patients remaining sputum positive during the first eight weeks (LOW quality evidence), and probably have no effect on weight gain during treatment (MODERATE quality evidence). No studies have assessed quality of life.Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, plasma levels of zinc, vitamin D and E, and selenium may be improved by supplementation during the early stages of tuberculosis treatment, but a consistent benefit on tuberculosis treatment outcomes or nutritional recovery has not been demonstrated. AUTHORS' CONCLUSIONS: There is insufficient research to know whether routinely providing free food or energy supplements results in better tuberculosis treatment outcomes, or improved quality of life. Further trials, particularly from food insecure settings, should have adequate sample sizes to identify, or exclude, clinically important benefits.Although blood levels of some vitamins may be low in patients starting treatment for active tuberculosis, there is currently no reliable evidence that routinely supplementing at or above recommended daily amounts has clinical benefits. PMID- 22071829 TI - Laparoscopic versus open nephrectomy for live kidney donors. AB - BACKGROUND: Waiting lists for kidney transplantation continue to grow and live organ donation has become more important as the number of brain stem dead cadaveric organ donors continues to fall. The major disincentive to potential kidney donors is the pain and morbidity associated with open surgery. OBJECTIVES: To identify the benefits and harms of using laparoscopic compared to open nephrectomy techniques to recover kidneys from live organ donors. SEARCH METHODS: We searched the online databases CENTRAL (in The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to January 2010) and EMBASE (January 1980 to January 2010) and handsearched textbooks and reference lists. SELECTION CRITERIA: Randomised controlled trials comparing laparoscopic donor nephrectomy (LDN) with open donor nephrectomy (ODN). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. MAIN RESULTS: Six studies were identified that randomised 596 live kidney donors to either LDN or ODN arms. All studies were assessed as having low or unclear risk of bias for selection bias, allocation bias, incomplete outcome data and selective reporting bias. Four of six studies had high risk of bias for blinding. Various different combinations of techniques were used in each study, resulting in heterogeneity in the results. The conversion rate from LDN to ODN ranged from 1% to 1.8%. LDN was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short-term consequences. ODN was associated with shorter duration of procedure. For those outcomes that could be meta analysed there were no significant differences between LDN or ODN for perioperative complications (RR 0.87, 95% CI 0.47 to 4.59), reoperations (RR 0.57, 95% CI 0.09 to 3.64), early graft loss (RR 0.31, 95% CI 0.06 to 1.48), delayed graft function (RR 1.09, 95% CI 0.52 to 2.30), acute rejection (RR 1.41, 95 % CI 0.87 to 2.27), ureteric complications (RR 1.51, 95% CI 0.69 to 3.31), kidney function at one year (SMD 0.15, 95% CI -0.11 to 0.41) or graft loss at one year (RR 0.76, 95% CI 0.15 to 3.85). AUTHORS' CONCLUSIONS: LDN is associated with less pain compared with open surgery; however, there are equivalent numbers of complications and occurrences of perioperative events that require further intervention. Kidneys obtained using LDN procedures were exposed to longer warm ischaemia periods than ODN-acquired grafts, although this has not been reported as being associated with short-term consequences. PMID- 22071830 TI - Antenatal breastfeeding education for increasing breastfeeding duration. AB - BACKGROUND: Breastfeeding (BF) is well recognised as the best food for infants. The impact of antenatal BF education on the duration of BF has not been evaluated. OBJECTIVES: To evaluate the effectiveness of antenatal BF education for increasing BF initiation and duration. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 April 2010), CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE (1966 to April 2010) and SCOPUS (January 1985 to April 2010). We contacted experts and searched reference lists of retrieved articles. We updated the search of the Pregnancy and Childbirth Group's Trials Register on 28 September 2011 and added the results to the awaiting classification section of the review. SELECTION CRITERIA: All identified published, unpublished and ongoing randomised controlled trials (RCTs) assessing the effect of formal antenatal BF education or comparing two different methods of formal antenatal BF education, on duration of BF. We excluded RCTs that also included intrapartum or postpartum BF education. DATA COLLECTION AND ANALYSIS: We assessed all potential studies identified as a result of the search strategy. Two review authors extracted data from each included study using the agreed form and assessed risk of bias. We resolved discrepancies through discussion. MAIN RESULTS: We included 17 studies with 7131 women in the review and 14 studies involving 6932 women contributed data to the analyses. We did not do any meta-analysis because there was only one study for each comparison.Five studies compared a single method of BF education with routine care. Peer counselling significantly increased BF initiation.Three studies compared one form of BF education versus another. No intervention was significantly more effective than another intervention in increasing initiation or duration of BF.Seven studies compared multiple methods versus a single method of BF education. Combined BF educational interventions were not significantly better than a single intervention in initiating or increasing BF duration. However, in one trial a combined BF education significantly reduced nipple pain and trauma.One study compared different combinations of interventions. There was a marginally significant increase in exclusive BF at six months in women receiving a booklet plus video plus lactation consultation (LC) compared with the booklet plus video only.Two studies compared multiple methods of BF education versus routine care. The combination of BF booklet plus video plus LC was significantly better than routine care for exclusive BF at three months. AUTHORS' CONCLUSIONS: Because there were significant methodological limitations and the observed effect sizes were small, it is not appropriate to recommend any antenatal BF education.There is an urgent need to conduct RCTs study with adequate power to evaluate the effectiveness of antenatal BF education. PMID- 22071831 TI - The effects of anaesthetic agents on cortical mapping during neurosurgical procedures involving eloquent areas of the brain. AB - BACKGROUND: In patients presenting for surgical resection of lesions involving, or adjacent to, the functionally important eloquent cortical areas, it is vital to achieve complete or near complete resection of the pathology without damaging the healthy surrounding tissues.The eloquent areas that the surgeons are concerned with are the primary motor, premotor cortex, supplementary motor cortex and speech areas. If the lesions are within these regions surgeons could either take a biopsy or do a intracapsular decompression without damaging the mentioned areas to avoid postoperative dysfunction. If the lesions are adjacent to the above mentioned areas, the normal anatomy would get distorted. However, proper identification of the above mentioned areas would enable the surgeon to radically remove the tumours. Intraoperative mapping of the cortex with stimulating and recording electrodes is termed as electrophysiological (EP) mapping.The EP mapping of motor, sensory and language cortex is widely employed in the resection of lesions involving or adjacent to the eloquent areas. Both intravenous and inhalational agents are known to affect these EP mapping techniques. OBJECTIVES: The aim of this review was to evaluate the effect of anaesthetic agents on intra operative EP mapping in patients undergoing neurosurgical procedures involving, or adjacent to, the functional areas of the cortex under general anaesthesia. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (7 March 2011), The Cochrane Central Register of Controlled Trials (CENTRAL issue 1 of 4, The Cochrane Library 2011), MEDLINE (Ovid, 1948 to February week 4, 2011), PsycINFO (EBSCOhost, 7 March 2011), and the National Research Register Archive and UK Clinical Research Network (7 March 2011). We also contacted other researchers in the field in an attempt to ascertain unpublished studies. SELECTION CRITERIA: We planned to include randomised and quasi randomised controlled trials irrespective of blinding in patients of any age or gender undergoing neurosurgery under general anaesthesia where cortical mapping was attempted to identify eloquent areas using either somatosensory evoked potentials (SSEPs), or direct cortical stimulation (DCS) triggered muscle motor evoked potentials (mMEPs), or both. We excluded patients from trials where the anaesthetic effects were evaluated during spinal cord surgery or where MEPs were recorded from modes other than direct cortical stimulation such as transcranial electrical stimulation (TcMEPs), MEPs derived from epidural electrodes (D waves) and magnetic stimulation and trials involving awake craniotomies or the asleep awake-asleep technique during cortical mapping. DATA COLLECTION AND ANALYSIS: Two review authors planned to independently apply the inclusion criteria and extract data. MAIN RESULTS: No RCTs were found for this study population. AUTHORS' CONCLUSIONS: This review highlights the need for well-designed randomised controlled trials to assess the effect of anaesthetic agents on cortical mapping during neurosurgical procedures involving eloquent areas of the brain. PMID- 22071832 TI - Methods of decreasing infection to improve outcomes after liver resections. AB - BACKGROUND: Infections cause both morbidity and mortality in patients undergoing liver resection. Various methods have been advocated to decrease the infectious complications after liver resection. We do not know if they are of any benefit to the patient or the health-care funder. OBJECTIVES: To determine the benefits and harms of different interventions in decreasing the infectious complications and improving the outcomes after liver resection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until August 2011. SELECTION CRITERIA: We included all randomised clinical trials that were performed to compare interventions aimed at decreasing the infectious complications after liver resection. DATA COLLECTION AND ANALYSIS: Two authors independently identified the trials and extracted the data. We analysed the data with both the fixed-effect and the random-effects model using RevMan Analysis. For each outcome we calculated the risk ratio (RR), rate ratio, or mean difference (MD) with 95% confidence intervals (CI) based on available patient data analysis. MAIN RESULTS: We included seven trials including 521 patients for this review. The sample size in the trials varied from 12 to 180 patients. All the trials were of high risks of systematic errors and of random errors. Four trials included patients who underwent liver resection only. In the remaining three trials, patients underwent combined liver resection with extrahepatic biliary resection resulting in a biliary enteric anastomosis. Four trials included only major liver resection. The remaining three trials included a mixture of major and minor liver resections. It appears that the proportion of cirrhotic patients in the trials was very low. The comparisons performed included whether antibiotics are necessary routinely during the peri-operative period of liver resection, the duration of antibiotics, the use of prebiotics and probiotics in the perioperative period, use of recombinant bactericidal-permeability increasing protein 21 (rBPI21), and the use of topical povidone iodine gel at the time of wound closure. Only one or two trials were included under each comparison. There was no significant differences in mortality or severe morbidity in any of the comparisons. Quality of life was not reported in any of the trials. AUTHORS' CONCLUSIONS: There is currently no evidence to support or refute the use of any treatment to reduce infectious complications after liver resections. Further well designed trials with low risk of systematic error and low risk of random errors are necessary. PMID- 22071833 TI - Xylitol for preventing acute otitis media in children up to 12 years of age. AB - BACKGROUND: Acute otitis media (AOM) is the most common bacterial infection among young children in the United States with limitations and concerns over its treatment with antibiotics and surgery. Therefore, effective preventative measures are attractive. A potential preventative measure is xylitol, a natural sugar substitute that reduces the risk for dental decay. Xylitol can reduce the adherence of Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) to nasopharyngeal cells in vitro. OBJECTIVES: To assess the efficacy and safety of xylitol to prevent AOM in children up to 12 years old. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August Week 1, 2011), EMBASE (1974 to August 2011), CINAHL (1982 to August 2011), Health and Psychosocial Instruments (1985 to August 2011), Healthstar (OVID) (1966 to August 2011) and International Pharmaceutical Abstracts (2000 to August 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of children aged 12 years or younger where xylitol supplementation was compared to placebo or no treatment to prevent AOM. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials from search results, assessed and rated study quality and extracted relevant data for inclusion in the review. We contacted trial authors to request missing data. We noted data on any adverse events of xylitol. We extracted data on relevant outcomes and estimated the effect size by calculating risk ratio (RR), risk difference (RD) and associated 95% confidence intervals (CI). MAIN RESULTS: We identified four studies of adequate methodological quality that met our eligibility criteria. In three RCTs with a total of 1826 healthy Finnish children attending day care, there was a reduced risk of occurrence of AOM in the xylitol group (in any form) compared to the control group (RR 0.75; 95% CI 0.65 to 0.88). The fourth RCT included 1277 Finnish day care children with a respiratory infection and found no effect of xylitol on reducing the occurrence of AOM (RR 1.13; 95% CI 0.83 to 1.53). Xylitol chewing gum was superior to xylitol syrup in preventing AOM among healthy children (RR 0.59; 95% CI 0.39 to 0.89) but not during respiratory infection (RR 0.68; 95% CI 0.43 to 1.07). There was no difference between xylitol lozenges and xylitol syrups in preventing AOM among healthy children (RR 0.77; 95% CI 0.53 to 1.11) or among children during respiratory infection (RR 0.74; 95% CI 0.47 to 1.14). Similarly, no difference was noted between xylitol chewing gum and xylitol lozenges in preventing AOM among healthy children (RR 0.73; 95% CI 0.47 to 1.13) or among children during respiratory infection (RR 0.92; 95% CI 0.59 to 1.46). Among the reasons for drop-outs, there were no significant differences in abdominal discomfort and rash between the xylitol and the control groups. AUTHORS' CONCLUSIONS: There is fair evidence that the prophylactic administration of xylitol among healthy children attending day care centres reduces the occurrence of AOM by 25%. This meta-analysis is limited since the data arise from a small number of studies, mainly from the same research group. PMID- 22071834 TI - Lasers or light sources for treating port-wine stains. AB - BACKGROUND: Port-wine stains are birthmarks caused by malformations of blood vessels in the skin. Port-wine stains manifest themselves in infancy as a flat, red mark and do not regress spontaneously but may, if untreated, become darker and thicker in adult life. The profusion of various lasers and light sources makes it difficult to decide which equipment is the best for treating port-wine stains. OBJECTIVES: To study participant satisfaction, clinical efficacy, and adverse effects of the treatment of port-wine stains by lasers and light sources. SEARCH METHODS: We searched the following databases up to April 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (Latin American and Caribbean Health Science Information database, from 1982), and reference lists of articles. We also searched online trials registries for ongoing trials and contacted trial authors where appropriate. SELECTION CRITERIA: Randomised clinical trials (RCTs) of lasers or light sources for the treatment of port-wine stains. DATA COLLECTION AND ANALYSIS: Our outcomes of interest were participant satisfaction, reduction in redness of the port-wine stain as determined by clinical evaluation, and short and long-term adverse effects of the treatments. Three authors independently extracted data and assessed trial quality. MAIN RESULTS: We included 5 RCTs involving a total of 103 participants; all of the trials used a within participant design. The interventions and outcomes were too varied to be combined statistically. All trials used the pulsed dye laser for comparisons.None of the studies focused on participant satisfaction, which was one of our primary outcomes, but participant preference was evaluated in three of five studies. Participants preferred the pulsed dye laser to intense pulsed light based on the clinical effect. They marginally preferred the Neodymium:YAG (yttrium-aluminium garnet) (Nd:YAG) laser to the pulsed dye laser due to shorter lasting purpura, and pulsed dye laser in conjunction with cooling was preferred to treatment with pulsed dye laser alone.All trials examined short-term efficacy of less than six months after treatments with the pulsed dye laser, intense pulsed light, and Nd:YAG laser. The pulsed dye laser was evaluated in all five trials. Depending upon the setting of the pulsed dye laser, this resulted in more than 25% reduction in redness. This was after 1 to 3 treatments for up to 4 to 6 months postoperatively in 50% to 100% of the participants. There was only one study each of intense pulsed light and Nd:YAG laser.Two trials had no occurrence of long term adverse effects, i.e. six months after treatment. Three trials reported pigmentary alterations in 3% to 24% of the participants, with the highest percentage occurring in Chinese participants with darker skin types. In one study one participant experienced scarring of the skin caused by a too-high dose of the laser used. Short-term side-effects included pain, crusting, and blistering in the first two weeks after treatment. AUTHORS' CONCLUSIONS: The pulsed dye laser leads to clinically relevant clearance of port-wine stains. A limited number of RCTs evaluated the efficacy from intense pulsed light and other laser types. High quality RCTs are needed to assess individual efficacy from different lasers and light sources, as well as participant satisfaction. PMID- 22071835 TI - Colorectal stents for the management of malignant colonic obstructions. AB - BACKGROUND: Colorectal cancer is one of the most common cancer in the western world. Acute colonic obstruction is one of the common presentations of colon cancer. Emergency surgical decompression is the traditional treatment of choice but is associated with high morbidity and mortality. In recent years colonic stents have been used to relieve the obstruction. OBJECTIVES: The aim was to compare the colonic stenting versus emergency surgical decompression with regards to benefits and risks. SEARCH METHODS: Searches were carried out May 2010 in the Cochrane Colorectal Cancer Specialised Register, the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid EMBASE and Ovid CINAHL. SELECTION CRITERIA: Randomised clinical trials comparing colonic stenting versus surgical decompression for obstructing colorectal cancers were considered for inclusion. DATA COLLECTION AND ANALYSIS: Data on the characteristics of the trial, methodological quality of the trials, mortality, morbidity, technical and clinical success rate, operating time, hospital stay and other measured secondary outcomes from each trial were collected. And the data were analysed with both the fixed-effect and the random-effects models using RevMan Analysis. For each outcome, odds ratio (OR) with 95% confidence intervals (CI) based on available data analysis was calculated. MAIN RESULTS: Five randomised trials were identified with a total of 207 participants, 102 to colorectal stenting and 105 to emergency surgery. There was statistically significant higher clinical success rate in the emergency surgery group. The average time of clinical relief of obstruction was 0.66 day in the colonic stent group and was 3.55 days in the emergency surgery group. The stent insertion was successful in 86.02% of attempted stent placements. There was no statistically significant difference in the 30-day mortality between two groups. The 30 day mortality rate was similar, 2.3% in both groups. The stent related perforation rate was 5.88%. The stent migration rate was 2.13%. The stent obstruction rate was 2.13%. There was no statistically significant difference in overall complication rate in both groups. The complication rate was 39.22% in the colonic stent group and was 45.71% in the emergency surgery group. The mean hospital stay was 11.53 days in the colonic stent group and was 17.15 days in the emergency surgery group. The mean procedure/operating time was 113.93 minutes in the colonic stent group compared to 143.85 minutes in the emergency surgery group. The median blood loss was 50 ml in the colonic stent group and 350 ml in the emergency surgery group. AUTHORS' CONCLUSIONS: The use of colonic stent in malignant colorectal obstruction seems to have no advantage over emergency surgery. The clinical success rate was statistically higher in emergency surgery group. However, use of colorectal stents seems to be as safe in the malignant colorectal obstruction as the emergency surgery with no statistically significant difference in the mortality and morbidity. Colorectal stents are associated with acceptable stent perforation, migration and obstruction rates. The advantages of colorectal stent includes shorter hospital stay and procedure time and less blood loss. However, due to the variability in the sample size and trial designs in the included studies, further randomised trials with bigger sample size and well defined trial design are needed to achieve the robust evidence. PMID- 22071836 TI - Mentoring adolescents to prevent drug and alcohol use. AB - BACKGROUND: Many adolescents receive mentoring. There is no systematic review if mentoring prevents alcohol and drug use. OBJECTIVES: Assess effectiveness of mentoring to prevent adolescent alcohol/drug use. SEARCH METHODS: Cochrane CENTRAL (issue 4), MEDLINE (1950-to July 2011), EMBASE (1980-to July 2011), 5 other electronic and 11 Grey literature electronic databases, 10 websites, reference lists, experts in addictions and mentoring. SELECTION CRITERIA: Randomised controlled trials (RCTs) of mentoring in adolescents to prevent alcohol/drug use. DATA COLLECTION AND ANALYSIS: We identified 2,113 abstracts, independently assessed 233 full-text articles, 4 RCTs met inclusion criteria. Two reviewers independently extracted data and assessed risks of bias. We contacted investigators for missing information. MAIN RESULTS: We identified 4 RCTs (1,194 adolescents). No RCT reported enough detail to assess whether a strong randomisation method was used or allocation was concealed. Blinding was not possible as the intervention was mentoring. Three RCTs provided complete data. No selective reporting.Three RCTs provided evidence about mentoring and preventing alcohol use. We pooled two RCTs (RR for mentoring compared to no intervention = 0.71 (95% CI = 0.57 to 0.90, P value = 0.005). A third RCT found no significant differences.Three RCTs provided evidence about mentoring and preventing drug use, but could not be pooled. One found significantly less use of "illegal" drugs," one did not, and one assessed only marijuana use and found no significant differences.One RCT measured "substance use" without separating alcohol and drugs, and found no difference for mentoring. AUTHORS' CONCLUSIONS: All four RCTs were in the US, and included "deprived" and mostly minority adolescents. Participants were young (in two studies age 12, and in two others 9-16). All students at baseline were non-users of alcohol and drugs. Two RCTs found mentoring reduced the rate of initiation of alcohol, and one of drug usage. The ability of the interventions to be effective was limited by the low rates of commencing alcohol and drug use during the intervention period in two studies (the use of marijuana in one study increased to 1% in the experimental and to 1.6% in the control group, and in another study drug usage rose to 6% in the experimental and 11% in the control group). However, in a third study there was scope for the intervention to have an effect as alcohol use rose to 19% in the experimental and 27% in the control group. The studies assessed structured programmes and not informal mentors. PMID- 22071837 TI - Active versus expectant management for women in the third stage of labour. AB - BACKGROUND: Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With expectant management, signs of placental separation are awaited and the placenta is delivered spontaneously. Active management was introduced to try to reduce haemorrhage, a major contributor to maternal mortality in low-income countries. OBJECTIVES: To compare the effectiveness of active versus expectant management of the third stage of labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (15 February 2011). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing active versus expectant management of the third stage of labour. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. MAIN RESULTS: We included seven studies (involving 8247 women), all undertaken in hospitals, six in high-income countries and one in a low-income country. Four studies compared active versus expectant management, and three compared active versus a mixture of managements. We used random-effects in the analyses because of clinical heterogeneity. There was an absence of high quality evidence for our primary outcomes. The evidence suggested that for women at mixed levels of risk of bleeding, active management showed a reduction in the average risk of maternal primary haemorrhage at time of birth (more than 1000 mL) (average risk ratio (RR) 0.34, 95% confidence interval (CI) 0.14 to 0.87, three studies, 4636 women) and of maternal haemoglobin (Hb) less than 9 g/dL following birth (average RR 0.50, 95% CI 0.30 to 0.83, two studies, 1572 women). We also found no difference in the incidence in admission of infants to neonatal units (average RR 0.81, 95% CI 0.60 to 1.11, two studies, 3207 women) nor in the incidence of infant jaundice requiring treatment (0.96, 95% CI 0.55 to 1.68, two studies, 3142 women). There were no data on our other primary outcomes of very severe postpartum haemorrhage (PPH) at the time of birth (more than 2500 mL), maternal mortality, or neonatal polycythaemia needing treatment.Active management also showed a significant decrease in primary blood loss greater than 500 mL, and mean maternal blood loss at birth, maternal blood transfusion and therapeutic uterotonics during the third stage or within the first 24 hours, or both and significant increases in maternal diastolic blood pressure, vomiting after birth, after-pains, use of analgesia from birth up to discharge from the labour ward and more women returning to hospital with bleeding (outcome not pre-specified). There was also a decrease in the baby's birthweight with active management, reflecting the lower blood volume from interference with placental transfusion.In the subgroup of women at low risk of excessive bleeding, there were similar findings, except there was no significant difference identified between groups for severe haemorrhage or maternal Hb less than 9 g/dL (at 24 to 72 hours).Hypertension and interference with placental transfusion might be avoided by using modifications to the active management package, e.g. omitting ergot and deferring cord clamping, but we have no direct evidence of this here. AUTHORS' CONCLUSIONS: Although there is a lack of high quality evidence, active management of the third stage reduced the risk of haemorrhage greater than 1000 mL at the time of birth in a population of women at mixed risk of excessive bleeding, but adverse effects were identified. Women should be given information on the benefits and harms of both methods to support informed choice. Given the concerns about early cord clamping and the potential adverse effects of some uterotonics, it is critical now to look at the individual components of third-stage management. Data are also required from low-income countries. PMID- 22071838 TI - Surgical interventions for diaphyseal fractures of the radius and ulna in children. AB - BACKGROUND: Diaphyseal forearm fractures in children are a common injury usually resulting from a fall. The treatment options include non-surgical intervention (manipulation and application of cast) and surgical options such as internal fixation with intramedullary nails or with plate and screws. OBJECTIVES: To assess the effects (benefits and harms) of a) surgical versus non-surgical interventions, and b) different surgical interventions for the fixation of diaphyseal fractures of the forearm bones in children. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (March 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 1), MEDLINE (1948 to February week 4 2011), EMBASE (1980 to 2011 week 09), trial registers and reference lists of articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared surgical with non-surgical intervention, or different types of surgical intervention for the fixation of diaphyseal forearm fractures in children. DATA COLLECTION AND ANALYSIS: All review authors independently examined the search results to identify trials for inclusion. MAIN RESULTS: After screening of 163 citations, we identified 15 potentially eligible studies of which 14 were excluded and one is an ongoing trial. There were thus no studies suitable for inclusion in this review. AUTHORS' CONCLUSIONS: There is a lack of evidence from randomised controlled trials to inform on when surgery is required and what type of surgery is best for treating children with fractures of the shafts of the radius, ulna or both bones. PMID- 22071839 TI - Omega-3 fatty acids supplementation for autism spectrum disorders (ASD). AB - BACKGROUND: It has been suggested that impairments associated with autism spectrum disorders (ASD) may be partially explained by deficits of omega-3 fatty acids, and that supplementation of these essential fatty acids may lead to improvement of symptoms. OBJECTIVES: To review the efficacy of omega-3 fatty acids for improving core features of ASD (for example, social interaction, communication, and stereotypies) and associated symptoms. SEARCH METHODS: We searched the following databases on 2 June 2010: CENTRAL (2010, Issue 2), MEDLINE (1950 to May Week 3 2010), EMBASE (1980 to 2010 Week 21), PsycINFO (1806 to current), BIOSIS (1985 to current), CINAHL (1982 to current), Science Citation Index (1970 to current), Social Science Citation Index (1970 to current), metaRegister of Controlled Trials (20 November 2008) and ClinicalTrials.gov (10 December 2010). Dissertation Abstracts International was searched on 10 December 2008, but was no longer available to the authors or editorial base in 2010. SELECTION CRITERIA: All randomised controlled trials of omega-3 fatty acids supplementation compared to placebo in individuals with ASD. DATA COLLECTION AND ANALYSIS: Three authors independently selected studies, assessed them for risk of bias and extracted relevant data. We conducted meta-analysis of the included studies for three primary outcomes (social interaction, communication, and stereotypy) and one secondary outcome (hyperactivity). MAIN RESULTS: We included two trials with a total of 37 children diagnosed with ASD who were randomised into groups that received either omega-3 fatty acids supplementation or a placebo. We excluded six trials because they were either non-randomised controlled trials, did not contain a control group, or the control group did not receive a placebo. Overall, there was no evidence that omega-3 supplements had an effect on social interaction (mean difference (MD) 0.82, 95% confidence interval (CI) -2.84 to 4.48, I(2) = 0%), communication (MD 0.62, 95% CI -0.89 to 2.14, I(2) = 0%), stereotypy (MD 0.77, 95% CI -0.69 to 2.22, I(2) = 8%), or hyperactivity (MD 3.46, 95% CI -0.79 to 7.70, I(2) = 0%). AUTHORS' CONCLUSIONS: To date there is no high quality evidence that omega-3 fatty acids supplementation is effective for improving core and associated symptoms of ASD. Given the paucity of rigorous studies in this area, there is a need for large well-conducted randomised controlled trials that examine both high and low functioning individuals with ASD, and that have longer follow-up periods. PMID- 22071840 TI - Lycopene for the prevention of prostate cancer. AB - BACKGROUND: Prostate cancer is a common cause of death in developed countries, yet the benefits of screening for prostate cancer still remain controversial. A prostate-specific antigen (PSA) test result greater than 4 ng/mL (nanograms/millilitre) has commonly been used as the cut-off level for seeking further tests to diagnose the presence (or absence) of prostate cancer. An increase in PSA levels may not necessarily be associated with an increased risk of prostate cancer, as PSA levels may also be increased in men with benign prostatic hyperplasia and prostatitis. Despite the uncertainty of the net benefit of early detection and treatment, safe and effective methods to prevent prostate cancer are of value. Consumers, seeking greater involvement in their healthcare, are increasingly turning to lifestyle modification and complementary and alternative medicines (CAMs) to maintain their health and prevent disease. Lycopene is a member of the carotenoid family, which is found abundantly in tomatoes, tomato-based products, strawberries, and watermelon. It has been hypothesised that lycopene is a strong antioxidant, which may lower the risk of cancer (including prostate cancer) in people who have diets rich in lycopene. OBJECTIVES: To determine whether lycopene reduces the incidence of prostate cancer and prostate cancer-specific mortality. Secondary objectives include changes in PSA levels, prostate symptoms and the nature of adverse events associated with lycopene use. SEARCH METHODS: Electronic searches were conducted across MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. No language or other limitations were imposed. SELECTION CRITERIA: Randomised controlled trials (RCTs) that investigated the use of lycopene for the prevention of prostate cancer were eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: A search of electronic databases, performed in August 2011, identified 64 citations. All articles were selected for full-text review. From these citations, three studies were identified as meeting the inclusion criteria. Handsearching did not provide any additional studies. MAIN RESULTS: Three RCTs, with a total of 154 participants were included in this review. None of the studies reported data on prostate cancer mortality. All of the included studies differed with respect to design, participants included and allocation of lycopene. This clinical heterogeneity limits the value on the pooled estimated of the meta-analyses. The methodological quality of two of the three included studies was assessed as posing a 'high' risk of bias. Meta analysis indicated no statistical difference in PSA levels between men randomised to receive lycopene and the comparison group (MD (mean difference) -0.34, 95% CI (confidence interval) -2.01, 1.32). Only one study reported incidence of prostate cancer (10% in the lycopene group versus 30% in control group). The level of lycopene was also not statistically different in men randomised to receive lycopene and the comparison group (MD 0.39 ug/mL (micrograms/millilitre), 95% CI 0.19, 0.98). No other meta-analyses were possible since other outcomes assessed only had one study contributing data. AUTHORS' CONCLUSIONS: Given that only three RCTs were included in this systematic review, and the high risk of bias in two of the three studies, there is insufficient evidence to either support, or refute, the use of lycopene for the prevention of prostate cancer. Similarly, there is no robust evidence from RCTs to identify the impact of lycopene consumption upon the incidence of prostate cancer, prostate symptoms, PSA levels or adverse events. PMID- 22071841 TI - Optimal intensity and type of leg exercise training for people with chronic obstructive pulmonary disease. AB - BACKGROUND: Intensity of exercise is considered a key determinant of training response, however, no systematic review has investigated the effects of different levels of training intensity on exercise capacity, functional exercise capacity and health-related quality of life (HRQoL) in people with chronic obstructive pulmonary disease (COPD). As type of training (continuous or interval) may also affect training response, the effects of the type of training in COPD also require investigation. OBJECTIVES: To determine the effects of training intensity (higher versus lower) or type (continuous versus interval training) on primary outcomes in exercise capacity and secondary outcomes in symptoms and HRQoL for people with COPD. SEARCH METHODS: We searched for studies in any language from the Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL, AMED, PsycINFO and PubMed. Searches were current as of June 2011. SELECTION CRITERIA: We included randomised controlled trials comparing higher training intensity to lower training intensity or comparing continuous training to interval training in people with COPD. We excluded studies that compared exercise training with no exercise training. DATA COLLECTION AND ANALYSIS: We pooled results of comparable groups of studies and calculated the treatment effect and 95% confidence intervals (CI) using a random-effects model. We made two separate comparisons of effects between: 1) higher and lower training intensity; 2) continuous and interval training. We contacted authors of missing data. MAIN RESULTS: We analysed three included studies (231 participants) for comparisons between higher and lower-intensity training and eight included studies (367 participants) for comparisons between continuous and interval training. Primary outcomes were outcomes at peak exercise (peak work rate, peak oxygen consumption, peak minute ventilation and lactate threshold), at isowork or isotime, endurance time on a constant work rate test and functional exercise capacity (six-minute walk distance). When comparing higher versus lower-intensity training, the pooled primary outcomes were endurance time and six-minute walk distance. There were no significant differences in endurance time improvement (mean difference (MD) 1.07 minutes; 95% CI -1.53 to 3.67) and six-minute walk distance improvement (MD 2.8 metres; 95% CI -10.1 to 15.6) following higher or lower-intensity training. However, heterogeneity of the endurance time results between studies was significant. When comparing continuous and interval training, there were no significant differences in any of the primary outcomes, except for oxygen consumption at isotime (MD 0.08; 95% CI 0.01 to 0.16) but the treatment effect was not considered clinically important. According to the GRADE system, studies were of low to moderate quality. AUTHORS' CONCLUSIONS: Comparisons between the higher and lower training intensity were limited due to the small number of included studies and participants. Consequently, there are insufficient data to draw any conclusions on exercise capacity, symptoms and HRQoL for this comparison. For comparisons between continuous and interval training, both appear to be equally effective in improving exercise capacity, symptoms and HRQoL. PMID- 22071842 TI - Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. AB - BACKGROUND: Chemotherapy has significantly improved prognosis for patients with malignant and some non-malignant conditions. This treatment, however, is associated with ovarian toxicity and gonadotropin-releasing hormone (GnRH) analogues may have a protective effect on the ovaries. The mechanism of action of GnRH is based on suppression of the gonadotropin levels to simulate pre-pubertal hormonal milieu and decrease utero-ovarian perfusion. OBJECTIVES: To assess the efficacy and safety of GnRH analogues given before or in parallel to chemotherapy to prevent chemotherapy-related ovarian damage in premenopausal women with malignant or non-malignant conditions. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Specialized Register (up to July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2011); MEDLINE (1950 to July 2011); EMBASE (1980 to July 2011); and the Chinese Biomedicine Database (CBM) (1976 to July 2011). SELECTION CRITERIA: Randomized controlled trials (RCTs), in all languages, which examined the effect of GnRH analogues for chemotherapy-induced ovarian failure in premenopausal women, were eligible for inclusion in the review. DATA COLLECTION AND ANALYSIS: The review authors independently extracted data and assessed trial quality using the Cochrane risk of bias tool. We analyzed binary data using risk ratios (RRs) with 95% confidence intervals (CI) and for continuous data, we used the standardized mean difference (SMD) to combine trials. As there was substantial difference in the types of chemotherapy used, we applied the random-effects model in our analyses. We contacted study authors for additional information. MAIN RESULTS: Included studies in this review showed that intramuscular/subcutaneous administration of GnRH agonists was effective in protecting menstruation and ovulation after chemotherapy (resumed menses: RR 1.90, 95% CI 1.30 to 2.79; amenorrhoea: RR 0.08, 95% CI 0.01 to 0.58; ovulation: RR 2.70, 95% CI 1.52 to 4.79), whereas intranasal administration of GnRH agonists had no protective effect on ovaries (resumed menses: RR 0.75, 95% CI 0.33 to 1.72; ovulation: RR 1.13, 95% CI 0.20 to 6.24). Pregnancy rates were not significantly different between groups (intramuscular/subcutaneous GnRH agonist: RR 0.21, 95% CI 0.01 to 4.09; intranasal GnRH agonist: RR 0.41, 95% CI 0.02 to 8.84). Ultrasound antral follicular count (AFC) was not significantly different between groups (SMD 1.11, 95% CI 0.32 to 1.90). AUTHORS' CONCLUSIONS: The use of GnRH agonists should be considered in women of reproductive age receiving chemotherapy. Intramuscular or subcutaneous GnRH analogues seem to be effective in protecting ovaries during chemotherapy and should be given before or during treatment, although no significant difference in pregnancy rates was seen. PMID- 22071843 TI - Mechanical dilatation of the cervix at non-labour caesarean section for reducing postoperative morbidity. AB - BACKGROUND: During non-labour caesarean, some obstetricians routinely dilate the cervix from above--using finger, sponge forceps or other instruments because they believe that the cervix of women without labour pain is undilated and may cause obstruction of blood or lochia drainage. However, mechanical cervical dilatation using sponge forceps or a finger during caesarean section may result in contamination by vaginal micro-organisms during dilatation, and increase the risk of infection or cervical trauma. OBJECTIVES: To determine the effects of mechanical dilatation of the cervix during elective/non-labour caesarean section on postoperative morbidity. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2011). SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing intraoperative cervical dilatation using a finger, sponge forceps or other instrument during non labour caesarean section versus no mechanical dilatation. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, assessed the risk of bias of each included study and extracted data. MAIN RESULTS: We included three trials with a total of 735 women undergoing elective caesarean section. Of these women, 338 underwent intraoperative cervical dilatation with a double-gloved index digit inserted into the cervical canal to dilate, and 397 did not undergo intraoperative cervical dilatation. Three included trials had moderate-to-high risk of bias. None of the three trials reported our primary outcome of postpartum haemorrhage. In one study of 400 women, blood loss was significantly lower in the cervical dilatation group compared with the no dilatation group (mean difference (MD) -48.49 ml, 95% confidence interval (CI) -88.75 to -8.23). The incidence of febrile morbidity and haemoglobin concentrations in the postoperative period in women undergoing intraoperative cervical dilatation was not significantly different from those who did not receive cervical dilatation (risk ratio (RR) 1.07, 95% CI 0.52 to 2.21 (three trials, 735 women) and MD -0.05 g/dl, 95% CI -0.17 to 0.06 (two trials, 552 women), respectively. There were no significant differences in wound infection, change of haemoglobin level, hematocrit level at postoperative period, endometritis, infectious morbidity, or urinary tract infection. There was a significant difference in operative time, which was reduced in cervical dilatation group (MD -1.84 mins, 95% CI -2.21 to -1.47 (one study, 400 women), but this is of doubtful clinical significance. AUTHORS' CONCLUSIONS: There was insufficient evidence of mechanical dilatation of the cervix at non-labour caesarean section for reducing postoperative morbidity. Further randomised controlled trials with adequate methodological quality comparing intraoperative cervical dilatation using a finger, sponge forceps or other instrument during non labour caesarean section versus no mechanical dilatation for reducing postoperative morbidity are needed. PMID- 22071844 TI - Surgical versus non-surgical interventions for treating patellar dislocation. AB - BACKGROUND: Patellar dislocation occurs when the patella disengages completely from the trochlear (femoral) groove. Following reduction of the dislocation, conservative rehabilitation with physiotherapy may be used. Since recurrence of dislocation is common, some surgeons have advocated surgical intervention in addition to rehabilitation. OBJECTIVES: The purpose of this review was to assess the clinical and radiological outcomes of surgical, compared with non-surgical, interventions for treating people with primary or recurrent patellar dislocation. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group's Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, AMED, CINAHL, ZETOC, Physiotherapy Evidence Database (PEDro), and a variety of other literature databases and trial registries. Corresponding authors were contacted to identify additional studies. Date searched: August 2010. SELECTION CRITERIA: Eligible for inclusion were randomised and quasi-randomised controlled clinical trials evaluating surgical versus non-surgical interventions for treating lateral patellar dislocation. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined titles and abstracts of each identified study to assess study eligibility, extract data and assess risk of bias. Primary outcomes assessed were the frequency of recurrent dislocation, and validated patient-rated knee or physical function scores. When appropriate, data were pooled. Risk ratios were calculated for dichotomous outcomes, and mean differences for continuous outcomes. MAIN RESULTS: Five studies (339 participants) were included. All studies had methodological shortcomings, especially the two quasi-randomised trials that presented a high risk for selection bias. Follow-up was a minimum of two years in two studies and between five and seven years in three studies. There was no significant difference between surgical and non-surgical management of primary (first-time) patellar dislocation in the risk of recurrent dislocation (47/182 versus 53/157; risk ratio 0.81, 95% confidence interval 0.56 to 1.17; 5 trials), Kujala patellofemoral disorder scores (mean difference 3.13, 95% confidence interval 7.34 to 13.59; 5 trials) nor the requirement for subsequent surgery (risk ratio 1.09, 95% CI 0.72 to 1.65; 3 trials). Adverse events were reported by one trial, citing four major complications that occurred in the surgical group. No randomised controlled trials have assessed populations with recurrent patellar dislocation. AUTHORS' CONCLUSIONS: There is insufficient high quality evidence to confirm any significant difference in outcome between surgical or non-surgical initial management of people following primary patellar dislocation, and none examining this comparison in people with recurrent patellar dislocation. Adequately powered randomised, multi-centre controlled trials, conducted and reported to contemporary standards are recommended. PMID- 22071845 TI - Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome). AB - BACKGROUND: Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare, X linked disease caused by a deficiency of the lysosomal enzyme iduronate-2 sulfatase, which catalyses a step in the catabolism of glycosaminoglycans. The glycosaminoglycans accumulate within tissues affecting multiple organs and physiologic systems. The clinical manifestations include neurologic involvement, severe airways obstruction, skeletal deformities and cardiomyopathy. The disease has a variable age of onset and variable rate of progression. In those with severe disease, death usually occurs in the second decade of life, whereas those patients with less severe disease may survive into adulthood. Enzyme replacement therapy with intravenous infusions of idursulfase has emerged as a new treatment for mucopolysaccharidosis type II. OBJECTIVES: To evaluate the effectiveness and safety of enzyme replacement therapy with idursulfase compared to other interventions, placebo or no intervention, for treating mucopolysaccharidosis type II. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (date of last search 01 September 2011).We also searched EMBASE, PubMed and the Literature Latino-Americana e do Caribe em Ciencias da Saude (LILACS) (date of last search October 2009). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of enzyme replacement therapy with idursulfase compared to no intervention, placebo or other options (e.g. behavioral strategies, transplantation). DATA COLLECTION AND ANALYSIS: Two authors independently screened the trials identified, appraised quality of papers and extracted data. MAIN RESULTS: One study (96 patients) met the inclusion criteria, although the primary outcome of this review - z score for height and weight, was not assessed in the study. Following 53 weeks of treatment, patients in the weekly idursulfase 0.5 mg/kg group demonstrated a significant improvement rate compared with placebo for the primary outcome: distance walked in six minutes on the basis of the sum of ranks of change from baseline, mean difference 37.00 (95% confidence interval 6.52 to 67.48). The every-other-week idursulfase 0.5 mg/kg group also showed an improvement, which was not significant compared with placebo, mean difference 23.00 (95% confidence interval -4.49 to 50.49). After 53 weeks, there was no statistical significance difference in per cent predicted forced vital capacity between the three groups and absolute forced vital capacity was significantly increased from baseline in the weekly dosing group compared to placebo, mean difference 0.16 (95% confidence interval CI 0.05 to 0.27). No difference was observed between the every-other-week idursulfase 0.5 mg/kg group and placebo.In addition, liver and spleen volumes and urine glycosaminoglycan excretion were significantly reduced from baseline by both idursulfase dosing regimens. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 31.7% of patients at the end of the study and they were related to a smaller reduction in urine glycosaminoglycan levels. AUTHORS' CONCLUSIONS: The current evidence is limited. While the randomised clinical trial identified was considered to be of good quality, it failed to describe important outcomes. It has been demonstrated that enzyme replacement therapy with idursulfase is effective in relation to functional capacity (distance walked in six minutes and forced vital capacity), liver and spleen volumes and urine glycosaminoglycan excretion in patients with mucopolysaccharidosis type II compared with placebo. There is no available evidence in the included study and in the literature on outcomes such as improvement in growth, sleep apnoea, cardiac function, quality of life and mortality. More studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy. PMID- 22071846 TI - Appendectomy versus antibiotic treatment for acute appendicitis. AB - BACKGROUND: Acute appendicitis is one of the most common causes of acute abdominal pain. Present day treatment of choice for acute appendicitis is appendectomy, however complications are inherent to operative treatment. Though surgical appendectomy remains the standard treatment, several investigators have investigated conservative antibiotic treatment of acute appendicitis and reported good results. OBJECTIVES: Is antibiotic treatment as effective as surgical appendectomy (laparoscopic or open) in patients with acute appendicitis on recovery within two weeks, without major complications (including recurrence) within one year? SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 6, 2011); MEDLINE (until June 2011); EMBASE (until June 2011); Prospective Trial Registers (June 2011) and reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised clinical trials (RCT and qRCT) comparing antibiotic treatment with appendectomy in patients with suspected appendicitis were included. Excluded were studies which primarily focused on the complications of acute appendicitis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager and MetaAnalyst. A non-inferiority analysis was performed, comparing antibiotic treatment (ABT) to the gold standard (appendectomy). By consensus, a 20% margin of non-inferiority was considered clinically relevant. MAIN RESULTS: Five RCT's (901 patients) were assessed. In total 73.4% (95% CI 62.7 to 81.9) of patients who were treated with antibiotics and 97.4 (95% CI 94.4 to 98.8) patients who directly got an appendectomy were cured within two weeks without major complications (including recurrence) within one year. The lower 95% CI was 15.2% below the 20% margin for the primary outcome. AUTHORS' CONCLUSIONS: The upper bound of the 95% CI of ABT for cure within two weeks without major complications crosses the 20% margin of appendectomy, so the outcome is inconclusive. Also the quality of the studies was low to moderate, for that reason the results should be interpret with caution and definite conclusions cannot be made. Therefore we conclude that appendectomy remains the standard treatment for acute appendicitis. Antibiotic treatment might be used as an alternative treatment in a good quality RCT or in specific patients or conditions were surgery is contraindicated. PMID- 22071847 TI - Helicobacter pylori eradication for Parkinson's disease. AB - BACKGROUND: Levodopa is the mainstay of treatment for alleviating the motor symptoms associated with Parkinson's disease. However, patients often experience fluctuations in their symptoms over time and 'wearing off' which may be partly related to variable absorption of the drug. There is some evidence that treatment of the common gastrointestinal infection Helicobacter pylori (H pylori) with antibiotics may improve levodopa absorption in the gut and hence improve symptoms. OBJECTIVES: 1) What is the prevalence of H pylori in Parkinson's disease patients? 2) Does treatment of H pylori infection with antibiotics improve symptoms in Parkinson's disease patients? Is this effect dependent on improvements in the absorption of levodopa? SEARCH METHODS: We searched electronic databases (including CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL) and trial registers, handsearched conference proceedings and carried out citation searching on key articles. All searching was updated in August 2009. We contacted authors to provide additional information where necessary. SELECTION CRITERIA: Clinical trials in patients with a well-defined definition of Parkinson's disease and who were H pylori-positive. Two people independently selected studies for inclusion using predetermined criteria. We used recruitment figures from clinical trials and other studies identified from the searching to determine the prevalence of H pylori in Parkinson's disease. DATA COLLECTION AND ANALYSIS: Two authors abstracted data from the source papers and assessed methodological quality independently. We presented results descriptively. MAIN RESULTS: Two completed and one ongoing clinical trial met the inclusion criteria. One trial (34 patients randomised) examined the effects of H pylori eradication on levodopa absorption and motor symptoms and found significant improvements in both. The ongoing trial has similar objectives and aims to recruit 100 patients. The other completed trial (20 patients analysed) sought to find a causal link between infection with H pylori and Parkinsonism and was non-contributory. A worsening of symptoms was noted with eradication failure.The prevalence of H pylori in Parkinson's disease was reported in four studies and ranged from 37% to 59% which is similar to that of the general population. AUTHORS' CONCLUSIONS: There is currently a lack of evidence on the effects of screening and treating H pylori in patients with Parkinson's disease. There is limited evidence to suggest that H Pylori eradication improves the absorption of levodopa and improves motor symptoms. Results from an ongoing trial will inform the evidence base and will be incorporated in an update of this review. There is a need for well-conducted randomised controlled trials with standard outcome measures for motor symptoms and incorporating the costs of screening and treatment. PMID- 22071848 TI - Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson's disease: evidence from observational studies. AB - BACKGROUND: Neuroinflammation may play a key role in the neurodegeneration associated with Parkinson's disease (PD). Non-steroidal anti-inflammatory drugs (NSAIDs) may be beneficial in the primary and secondary prevention of PD. OBJECTIVES: 1) Do NSAIDs prevent the onset of PD?2) Are NSAIDs neuroprotective in PD - do they slow the progression of disease once PD is established?3) What are the adverse effects of taking NSAIDs in PD? SEARCH METHODS: We searched electronic databases, including trial registers, complemented with handsearching of conference proceedings and citation searching on key articles. All searching was updated in May 2011. We contacted authors to provide additional information where necessary. SELECTION CRITERIA: For the primary prevention review, we sought primary prevention trials and observational studies (cohort and case-control studies). Participants were free of PD when exposure to NSAIDs was assessed. For the secondary prevention review, we sought clinical trials in patients with a well-defined definition of PD. Two people independently selected studies for inclusion using predetermined criteria. DATA COLLECTION AND ANALYSIS: Two review authors abstracted data from the source papers and assessed methodological quality independently. No studies met the inclusion criteria for the secondary prevention review. For the primary prevention review only observational studies were found. We combined data where appropriate using the inverse variance method. We assessed methodological quality using the Newcastle Ottawa Scales and by examining the period of exposure assessed prior to PD onset (or the index date in controls). MAIN RESULTS: Fourteen observational studies met the inclusion criteria for the primary prevention review (five cohort, nine case-control studies). Exposure to any NSAIDs or aspirin had no effect on the risk of developing PD. Exposure to non-aspirin NSAIDs reduced the risk of developing PD by 13% (effect estimate 0.87 (95% CI 0.73 to 1.04 - random-effects model), but this did not reach statistical significance. We found similar results for the most robust studies. Ibuprofen in isolation was examined in four studies and was associated with a 27% reduction in risk (effect estimate 0.73, 95% CI 0.63 to 0.85). There was a lack of information on adverse effects. AUTHORS' CONCLUSIONS: There is currently no evidence for the use of NSAIDs in the secondary prevention of PD. Non-aspirin NSAIDs, particularly ibuprofen, may reduce the risk of developing PD. However, little is known of the effects of other individual drugs and at present no recommendations can be made regarding their use in primary prevention. PMID- 22071849 TI - Psychosocial interventions for the management of chronic orofacial pain. AB - BACKGROUND: Psychosocial factors have a role in the onset of chronic orofacial pain. However, current management involves invasive therapies like occlusal adjustments and splints which lack an evidence base. OBJECTIVES: To determine the efficacy of non-pharmacologic psychosocial interventions for chronic orofacial pain. SEARCH METHODS: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 25 October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE via OVID (1950 to 25 October 2010), EMBASE via OVID (1980 to 25 October 2010) and PsycINFO via OVID (1950 to 25 October 2010). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: Randomised controlled trials which included non-pharmacological psychosocial interventions for adults with chronic orofacial pain compared with any other form of treatment (e.g. usual care like intraoral splints, pharmacological treatment and/or physiotherapy). DATA COLLECTION AND ANALYSIS: Data were independently extracted in duplicate. Trial authors were contacted for details of randomisation and loss to follow-up, and also to provide means and standard deviations for outcome measures where these were not available. Risk of bias was assessed and disagreements between review authors were discussed and another review author involved where necessary. MAIN RESULTS: Seventeen trials were eligible for inclusion into the review. Psychosocial interventions improved long-term pain intensity (standardised mean difference (SMD) -0.34, 95% confidence interval (CI) -0.50 to -0.18) and depression (SMD -0.35, 95% CI -0.54 to -0.16). However, the risk of bias was high for almost all studies. A subgroup analysis revealed that cognitive behavioural therapy (CBT) either alone or in combination with biofeedback improved long-term pain intensity, activity interference and depression. However the studies pooled had high risk of bias and were few in number. The pooled trials were all related to temporomandibular disorder (TMD). AUTHORS' CONCLUSIONS: There is weak evidence to support the use of psychosocial interventions for chronic orofacial pain. Although significant effects were observed for outcome measures where pooling was possible, the studies were few in number and had high risk of bias. However, given the non-invasive nature of such interventions they should be used in preference to other invasive and irreversible treatments which also have limited or no efficacy. Further high quality trials are needed to explore the effects of psychosocial interventions on chronic orofacial pain. PMID- 22071850 TI - Melatonin for non-respiratory sleep disorders in visually impaired children. AB - BACKGROUND: Exogenous melatonin helps in regulating the circadian rhythm and is widely used for the management of sleep disorders in visually impaired children. OBJECTIVES: The aim of the review was to assess melatonin therapy for treatment of non-respiratory sleep disorders in visually impaired children, with regard to improvement in sleep habit, sleep scheduling and sleep maintenance, when compared with placebo or no treatment. SEARCH METHODS: We searched the following databases between February 2011 and July 2011: the Cochrane Central Register of Controlled Trials (CENTRAL) 2011(1) searched on 4th February 2011; MEDLINE (1950 to June Week 3, 2011) searched on 20th June 2011; EMBASE (1980 to June Week 4, 2011) searched on 7th July 2011; CINAHL (1937 to 21 September 2011); the metaRegister of Controlled Trials (this includes ClinicalTrial.gov) searched 20 July 2011, and reference lists of papers identified after initial screening. SELECTION CRITERIA: We planned to include randomized controlled trials (RCTs) and quasi-RCTs, including cross-over studies. Treatment would be exogenous melatonin. Control groups could be placebo, other medication for sleep disorders or no treatment. Outcomes sought were improved sleep with regard to timing and duration, quality of life and adverse events. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion in the review. MAIN RESULTS: We did not find any studies fulfilling the inclusion criteria, therefore no outcome data are reported.We identified nine studies after initial screening and, after further evaluation, we excluded these. The excluded studies involved a total of 163 individuals aged two years to 18 years. We excluded studies for three main reasons: they were non-randomized or case series studies, they were studies of people over 18 years of age or even where the study was randomised, the study population was mixed and results pertaining to the visually impaired cohort could not be independently evaluated. No significant adverse effects of melatonin were reported in these excluded studies. AUTHORS' CONCLUSIONS: There is currently no high quality data to support or refute the use of melatonin for sleep disorders in visually impaired children. Placebo-controlled trials examining important clinical outcomes such as sleep quality, sleep latency, duration of sleep and night-time awakenings are needed. As the numbers of children meeting study inclusion criteria are likely to be low at individual sites, multicentre collaboration between developmental paediatricians, sleep physicians and other health care professionals is essential to achieve sufficient sample size for controlled studies. Such collaboration would help facilitate local recruitment at multiple sites, with study oversight being provided by paediatricians with expertise in sleep disorders. Participation of collaborators with experience in evidence-based practice research is also desirable due to the lack of protocols on melatonin therapy in the target population. PMID- 22071851 TI - Pharmacological interventions for the treatment of anxiety disorders in chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterised by inflammation of the airways and destruction of pulmonary tissue with post bronchodilator FEV1/FVC of <0.70 (forced expiratory volume in one second/forced vital capacity). Evidence indicates an increased prevalence of anxiety disorders in patients with chronic obstructive pulmonary disease (COPD), as compared with the general population and persons suffering from many other chronic illnesses. Anxiety in people with COPD has been shown to increase disability and impair functional status, resulting in an overall reduction in quality of life. As such, pharmacological interventions are commonly used to treat anxiety disorders in patients with COPD. OBJECTIVES: To assess the effect of pharmacological interventions on anxiety disorders in people with COPD, in terms of improvement of anxiety symptoms, quality of life, exercise tolerance, reduction in length of hospital stay and FEV1. We also evaluated adverse drug reactions. SEARCH METHODS: Two Cochrane Review Group Specialised Registers were searched (up to the 1st of June 2011) to identify trials for this review. Complementary searches of PsycINFO and the Cochrane Central Register of Controlled Trials (CENTRAL) were also carried out. We did not apply any language restrictions. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs), cluster randomised trials and cross-over trials of pharmacological interventions for patients (age > 40 years) with COPD and co-existing anxiety disorders (as confirmed by recognised diagnostic criteria or a validated measurement scale) for the review. DATA COLLECTION AND ANALYSIS: Two of the three review authors individually evaluated each article and extracted data. Any conflicts that arose were resolved through discussion with a third party, if necessary. Trial investigators were contacted to obtain missing/raw data. Meta-analyses of continuous outcomes were performed using the random-effect model. MAIN RESULTS: Four studies met all of the inclusion criteria (with a total of 40 participants). Three subclasses of anxiety medications were used including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and azapirones. Although two studies used SSRIs as the intervention (total of 21 participants), we were unable to meta-analyse the anxiety outcomes as one study had a standard deviation of zero for the control group. Included studies had relatively poor quality including small sample sizes and short follow-up periods. Due to the small number of included studies, we were unable to meta-analyse all the subclasses of medications. AUTHORS' CONCLUSIONS: Due to the sub-optimal quality of the trials and statistically non-significant results, it is not possible to draw any conclusions for treatment. This review highlights the paucity of data in this area. As such, there is a need for scientifically rigorous research trials to evaluate the role of pharmacological interventions for anxiety disorders in patients with COPD, using a sample size large enough to demonstrate meaningful clinical significance. PMID- 22071852 TI - Anti-hypertensive drugs as disease-modifying agents for Parkinson's disease: evidence from observational studies and clinical trials. AB - BACKGROUND: Current treatment for Parkinson's disease (PD) is focused on relieving symptoms, at present there is nothing that is widely accepted to halt or slow disease progression. Potential neuroprotective or disease modifying agents have been identified from preclinical studies. One such group of compounds are anti-hypertensive drugs. OBJECTIVES: 1) Do anti-hypertensive drugs prevent the onset of PD? (primary prevention)2) Are anti-hypertensive drugs disease modifying agents in PD, do they slow the progression of disease once PD is established? (secondary prevention)3) What are the adverse effects of taking anti hypertensive drugs for patients with PD? SEARCH METHODS: Electronic databases including trial registers were searched, complemented with handsearching of conference proceedings and searching the citations of key articles (updated May 2011). Authors were contacted, to provide additional information, where necessary. SELECTION CRITERIA: For the primary prevention review, primary prevention trials and observational studies (cohort and case control studies) were sought. Participants were free of PD when exposure to anti-hypertensive drugs was assessed. For the secondary prevention review, clinical trials in patients with well defined PD were sought. Two people independently selected studies for inclusion using predetermined criteria. DATA COLLECTION AND ANALYSIS: Data were abstracted from the source papers and methodological quality was assessed independently by two review authors. Results for both reviews were dealt with descriptively. MAIN RESULTS: Two cohort studies and four case control studies met the inclusion criteria for the primary prevention review. The two cohort studies found no effect of exposure to calcium channel blockers on the risk of developing PD. Three case control studies looked at the effects of exposure to calcium channel blockers and beta blockers on the risk of developing PD but the assessment periods of exposure were markedly different prior to PD onset, and different subclasses of drugs were examined, so results were not comparable. A protective effect of centrally acting calcium channel blockers was found in one study.Two trials and one ongoing trial met the inclusion criteria for the secondary prevention review. Each completed trial examined a different class of anti-hypertensive drug. The ongoing trial is examining the effects of the calcium channel blocker isradipine on motor symptoms and disease progression. It follows an earlier tolerability study. The results are due in the year 2012.Adverse effects were noted in all included trials and included intolerability to the drugs and worsening PD symptoms. AUTHORS' CONCLUSIONS: There is currently a lack of evidence for the use of antihypertensive drugs for either the primary or secondary prevention of PD. More observational studies are required to identify potential drugs to go forward for safety and tolerability studies in people with early PD. The results of the ongoing trial will help inform further research. PMID- 22071853 TI - Sargramostim (GM-CSF) for induction of remission in Crohn's disease. AB - BACKGROUND: Crohn's disease is an inflammatory condition of the gut, thought to involve an overactive immune response to gut flora. A novel theory postulates possible immunodeficiency as a cause, and aims to use sargramostim (granulocyte macrophage colony stimulating factor, GM-CSF) to boost the immune system in an effort to test this hypothesis. OBJECTIVES: The primary objectives were to determine the efficacy and safety of sargramostim for induction of remission in patients with clinically active Crohn's disease. SEARCH METHODS: A systematic search of MEDLINE, EMBASE, and CENTRAL was conducted from inception to April 2011. Reference lists of relevant review articles were also searched. Trial registries and abstract databases including Digestive Diseases Week (1980-2010) and United European Gastroenterology Week (2005-2009) were searched to identify studies published in abstract form. SELECTION CRITERIA: Randomized controlled trials of sargramostim for the treatment of patients with active Crohn's disease were considered for inclusion. DATA COLLECTION AND ANALYSIS: Data from selected articles were extracted and the Cochrane Risk of Bias tool applied independently by two authors. The primary outcome was induction of clinical remission as defined by a Crohn's Disease Activity Index (CDAI) of < 150 at the end of treatment. Secondary outcomes included clinical responses measures on the CDAI and safety outcomes. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes, in most cases using a random effects model due to high heterogeneity. MAIN RESULTS: Three studies were identified, 2 published as full papers and one in abstract form (537 patients). The risk of bias was low for the 3 included studies. There was no statistically significant difference in the proportion of patients (GM-CSF 25.3% versus placebo 17.5%) who achieved clinical remission (RR 1.67; 95% CI 0.80 to 3.50; P = 0.17; 3 studies; 537 patients). There was no statistically significant difference in the proportion of patients (GM-CSF 38.3% versus placebo 24.8%) who achieved a 100 point clinical response (RR 1.71 95% CI 0.98 to 2.97; P = 0.06; 3 studies; 537 patients). There was no statistically significant difference in the proportion of patients (GM-CSF 54.3% versus placebo 44.2%) who achieved a 70 point clinical response (RR 1.23; 95% CI 0.83 to 1.82; P = 0.30; 1 study; 124 patients). There was no statistically significant difference in the proportion of patients (GM-CSF 95.8% versus placebo 89.3%) who experienced at least one adverse event (RR 1.07; 95% CI 0.99 to 1.16; P = 0.08; 2 studies; 251 patients), or serious adverse events (GM-CSF 12.0% versus placebo 4.8%; RR 2.21; 95% CI 0.84 to 5.81; P = 0.11; 2 studies; 251 patients). The incidence of bone pain, musculoskeletal chest pain, and dyspnea were higher in patients treated with sargramostim compared to placebo. Other adverse events commonly associated with sargramostim such as pulmonary capillary leak syndrome, pulmonary edema, heart failure, fever, and neurotoxicity were not reported in these studies. AUTHORS' CONCLUSIONS: Sargramostim does not appear to be more effective than placebo for induction of clinical remission or clinical improvement in patients with active Crohn's disease. However, the GRADE analysis indicates that the overall quality of the evidence for the primary (clinical remission) and secondary outcomes (clinical response) was low indicating that further research is likely to have an impact on the effect estimates. PMID- 22071854 TI - Analgesia for amniocentesis or chorionic villus sampling. AB - BACKGROUND: Besides risks of miscarriage, pregnant women undergoing amniocentesis or chorionic villus sampling (CVS) are also concerned about pain associated with these procedures. Currently, approaches to analgesia can be categorised in two broad categories - non-pharmacological and pharmacological agents. OBJECTIVES: To evaluate whether different methods of analgesia have any impact on pain reduction during amniocentesis or chorionic villus sampling (CVS). SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2011). SELECTION CRITERIA: All randomised trials comparing different method of analgesia for amniocentesis or CVS. We also include trials with quasi-randomised designs, but analyse and report their results separately. DATA COLLECTION AND ANALYSIS: Both review authors assessed eligibility and trial quality and performed data extraction. MAIN RESULTS: We included a total of five randomised studies (involving 805 women) evaluating different methods of analgesia for amniocentesis; there were no studies in women undergoing CVS.One RCT (N = 203) and one quasi-randomised study (N = 220) compared infiltrative local anaesthesia with no anaesthesia and found no statistical difference in experienced pain on the visual analogue scale (VAS) (mean differences (MD) -2.50 and 1.20; 95% confidence interval (CI) -6.98 to 1.98 and -2.67 to 5.07).One study (N = 200) compared light leg rubbing versus no intervention during amniocentesis and found no change in experienced anxiety (MD 0.2; 95% CI -0.63 to 1.03) or VAS pain score (MD 0.3; 95% CI -0.35 to 0.95) during amniocentesis.Another study with 62 patients did not find any benefit of using subfreezing temperature needle during amniocentesis in terms of decreased VAS pain score (MD -0.8; 95% CI -1.8 to 0.2). In addition, there was no difference between anticipated and actual pain (MD 0.4; 95% CI -0.82 to 1.62) (before/after comparison).There was also no difference in VAS pain scores in the study with 120 participants comparing lidocaine-prilocaine analgesic cream to placebo cream before amniocentesis (MD -0.6; 95% CI -1.44 to 0.24). AUTHORS' CONCLUSIONS: In general, women who undergo amniocentesis could be informed that pain during procedure is minor and that there is currently insufficient evidence to support the use of local anaesthetics, leg rubbing or subfreezing the needle for pain reduction during procedure. PMID- 22071855 TI - Probiotics for patients with hepatic encephalopathy. AB - BACKGROUND: Hepatic encephalopathy is a disorder of brain function as a result of liver failure and/or portosystemic shunt. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient's quality of life and daily functioning and represent a significant burden on health care resources. Probiotics are live microorganisms, which when administered in adequate amounts may confer a health benefit on the host. OBJECTIVES: To quantify the beneficial and harmful effects of any probiotic in any dosage, compared with placebo or no intervention, or with any other treatment for patients with any grade of acute or chronic hepatic encephalopathy as assessed from randomised trials. SEARCH METHODS: We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, conference proceedings, reference lists of included trials and the WHO international clinical trials registry until April 2011 registry platform to identify new and ongoing trials. SELECTION CRITERIA: We included randomised trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in patients with hepatic encephalopathy. DATA COLLECTION AND ANALYSIS: Three authors independently assessed the risk of bias of the included trials and extracted data on relevant outcomes, with differences resolved by consensus. We conducted random-effects model meta-analysis due to obvious heterogeneity of patients and interventions. A P value of 0.05 or less was defined as significant. Dichotomous outcomes are expressed as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: We included seven trials of which 550 participants were randomised. Four of the seven trials compared a probiotic with placebo or no treatment in 245 participants, another trial compared a probiotic with lactulose in 40 participants , and the remaining two trials compared a probiotic with both placebo and lactulose in 265 participants. Each trial used different types of probiotics. Duration of administration of the experimental intervention varied from 10 days to 180 days. Two trials were industry funded, and five were unclear about origin of funding. All trials had high risk of bias. When probiotics were compared with no treatment, there was no significant difference in all-cause mortality (2 trials, 105 participants; 1/57 (2%) versus 1/48 (2%): RR 0.72; 95% CI 0.08 to 6.60), lack of recovery (4 trials, 206 participants; 54/107 (50%) versus 68/99 (69%): RR 0.72; 95% CI 0.49 to 1.05), adverse events (3 trials, 145 participants; 2/77 (3%) versus 6/68 (9%): RR 0.34; 95% CI 0.08 to 1.42), quality of life (1 trial, 20 participants contributed to the physical quality of life measurement, 20 participants contributed to the mental quality of life: MD Physical 0.00; 95% CI -5.47 to 5.47; MD Mental 4.00; 95% CI -1.82 to 9.82), or change of/or withdrawal from treatment (3 trials, 175 participants; 11/92 (12%) versus 7/83 (8%): RR 1.28; 95% CI 0.52 to 3.19). No trial reported sepsis or duration of hospital stay as an outcome. Plasma ammonia concentration was significantly lower for participants treated with probiotic at one month (3 trials, 226 participants: MD -2.99 MUmol/L; 95% CI -5.70 to -0.29) but not at two months (3 trials, 181 participants: MD -1.82 MUmol/L; 95% CI 14.04 to 10.41). Plasma ammonia decreased the most in the participants treated with probiotic at three months (1 trial, 73 participants: MD -6.79 MUmol/L; 95% CI -10.39 to -3.19). When probiotics were compared with lactulose no trial reported all-cause mortality, quality of life, duration of hospital stay, or septicaemia. There were no significant differences in lack of recovery (3 trials, 173 participants; 47/87 (54%) versus 44/86 (51%): RR 1.05; 95% CI 0.75 to 1.47), adverse events (2 trials, 111 participants; 3/56 (5%) versus 6/55 (11%): RR 0.57; 95% CI 0.06 to 5.74), change of/or withdrawal from treatment at one month (3 trials, 190 participants; 8/95 (8%) versus 7/95 (7%): RR 1.10; 95% CI 0.40 to 3.03), plasma ammonia concentration (2 trials, 93 participants: MD -6.61 MUmol/L; 95% CI -30.05 to 16.84), or change in plasma ammonia concentration (1 trial, 77 participants: MD 1.16 MUmol/L; 95% CI -1.96 to 4.28). AUTHORS' CONCLUSIONS: The trials we located suffered from a high risk of systematic errors ('bias') and high risk of random errors ('play of chance'). While probiotics appear to reduce plasma ammonia concentration when compared with placebo or no intervention, we are unable to conclude that probiotics are efficacious in altering clinically relevant outcomes. Demonstration of unequivocal efficacy is needed before probiotics can be endorsed as effective therapy for hepatic encephalopathy. Further randomised clinical trials are needed. PMID- 22071856 TI - Oral health advice for people with serious mental illness. AB - BACKGROUND: People with serious mental illness experience an erosion of functioning in day-to-day life over a protracted period of time. There is also evidence to suggest that people with serious mental illness have a greater risk of experiencing oral disease and have greater oral treatment needs than the general population. However, oral health has never been seen as a priority in people suffering with serious mental illness. Poor oral health has a serious impact on quality of life, everyday functioning, social inclusion and self esteem. We feel that oral healthcare advice could have a positive impact on this disadvantaged population. OBJECTIVES: To assess the effectiveness of oral health advice in reducing morbidity, mortality and preserving the quality of life in people with serious mental illness. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (October 2009) which is based on regular searches of CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO. SELECTION CRITERIA: We planned to include all randomised clinical trials focusing on oral health advice versus standard care or comparing oral health advice with other more focused methods of delivering care or information. DATA COLLECTION AND ANALYSIS: The review authors (GT, AC, WK) independently screened search results and did not identify any studies that fulfilled the review's criteria. MAIN RESULTS: We did not identify any studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: Healthcare professionals should be more proactive in liaising with oral health professionals in developing novel ways to cater for the needs of people with serious mental illness. PMID- 22071857 TI - Compression stockings for the initial treatment of varicose veins in patients without venous ulceration. AB - BACKGROUND: Compression hosiery or stockings are often the first line of treatment for varicose veins in people without either healed or active venous ulceration. Evidence is required to determine whether the use of compression stockings can effectively manage and treat varicose veins in the early stages. OBJECTIVES: To assess the effectiveness of compression stockings for the initial treatment of varicose veins in patients without healed or active venous ulceration. SEARCH METHODS: The Cochrane Peripheral Vascular Disease Group searched their Specialised Register (last searched 31 May 2011) and CENTRAL (2011, Issue 2). In addition, the reference lists of relevant articles were searched. Authors of ongoing and current trials were contacted. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) were included if they involved participants diagnosed with primary trunk varicose veins without healed or active venous ulceration (Clinical, Etiology, Anatomy, Pathophysiology (CEAP) classification C2 to C4). Included trials assessed compression stockings versus no treatment, compression versus placebo stockings, or compression stockings + drug intervention versus drug intervention alone. Trials comparing different lengths and pressures of stockings were also included. Trials involving other types of treatment for varicose veins (either as a comparator to stockings or as an initial non-randomised treatment), including sclerotherapy and surgery, were excluded. DATA COLLECTION AND ANALYSIS: Two authors assessed the trials for inclusion and quality (SS and LR). SS extracted the data, which were checked by LR. Attempts were made to contact trial authors where missing or unclear data were present. MAIN RESULTS: Seven studies involving 356 participants with varicose veins without healed or active venous ulceration were included. Different levels of pressure were exerted by the stockings in the studies, ranging from 10 to 50 mmHg. One study assessed compression hosiery versus no compression hosiery. The other six compared different types or pressures of stockings. The methodological quality of all included trials was unclear, mainly because of inadequate reporting.The symptoms subjectively improved with the wearing of stockings across trials that assessed this outcome, but these assessments were not made by comparing one randomised arm of a trial with a control arm and are therefore subject to bias.Meta-analyses were not undertaken due to inadequate reporting and actual or suspected high levels of heterogeneity. AUTHORS' CONCLUSIONS: There is insufficient, high quality evidence to determine whether or not compression stockings are effective as the sole and initial treatment of varicose veins in people without healed or active venous ulceration, or whether any type of stocking is superior to any other type. Future research should consist of a large RCT of participants with trunk varices either wearing or not wearing compression stockings to assess the efficacy of this intervention. If compression stockings are found to be beneficial, further studies assessing which length and pressure is the most efficacious could then take place. PMID- 22071858 TI - Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). AB - BACKGROUND: Methotrexate is routinely used in the treatment of inflammatory arthritis. There have been concerns regarding the safety of using concurrent non steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or paracetamol (acetaminophen), or both, in these people. OBJECTIVES: To systematically appraise and summarise the scientific evidence on the safety of using NSAIDs, including aspirin, or paracetamol, or both, with methotrexate in inflammatory arthritis; and to identify gaps in the current evidence, assess the implications of those gaps and to make recommendations for future research to address these deficiencies. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, second quarter 2010); MEDLINE (from 1950); EMBASE (from 1980); the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) (2008 to 2009) and checked the websites of regulatory agencies for reported adverse events, labels and warnings. SELECTION CRITERIA: Randomised controlled trials and non-randomised studies comparing the safety of methotrexate alone to methotrexate with concurrent NSAIDs, including aspirin, or paracetamol, or both, in people with inflammatory arthritis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the search results, extracted data and assessed the risk of bias of the included studies. MAIN RESULTS: Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis using various NSAIDs, including aspirin. There were no identified studies for other forms of inflammatory arthritis.For NSAIDs, 13 studies were included that used concurrent NSAIDs, of which nine studies examined unspecified NSAIDs. The mean number of participants was 150.4 (range 19 to 315), mean duration 2182.9 (range 183 to 5490) days, although the study duration was not always clearly defined, and the studies were mainly of low to moderate quality. Two of these studies reported no evidence for increased risk of methotrexate induced pulmonary disease; one study assessed the effect of concurrent NSAIDs on renal function and found no adverse effect; one study identified no adverse effect on liver function; three studies demonstrated no increase in methotrexate withdrawal; and one study showed no increase in all adverse events, including major toxic reactions. However, transient thrombocytopenia was demonstrated in one study, specifically when NSAIDs were taken on the same week day as methotrexate. This study was a retrospective review that involved small numbers only and was of moderate quality; these finding have not been replicated since.Four studies looked at specific NSAIDs (etodolac, piroxicam, celecoxib and etoricoxib), with a mean number of participants of 25.8 (range 14 to 50) and mean study duration of 16.8 (range 14 to 23) days. These studies were mainly of moderate quality. The studies were primarily pharmacokinetic studies but also reported adverse events as secondary outcomes. There were no clinically significant adverse effects with concomitant piroxicam or etodolac; and only mild adverse events with celecoxib or etoricoxib, such as nausea and vomiting, and headaches.For aspirin, seven studies provided data on adverse events with the use of aspirin and methotrexate. These studies included a mean number of participants of 100 (range 11 to 232), had a mean duration of 1325 (range 8 to 2928) days and were mainly of low to moderate quality. Two of the studies reported no evidence for increased risk of methotrexate-induced pulmonary disease and two studies showed no increase in all adverse events including major toxic reactions; however, none of these studies specified the dose of aspirin that was used. One study demonstrated that concurrent aspirin adversely affected liver function at a mean dose of 6.84 tablets of aspirin per day, which is a possible daily dose of 2.1 g presuming that 300 mg aspirin tablets were given. A further study described a partially reversible decline in renal function with 2 g daily of aspirin. One study reported no increase in adverse events with 975 g aspirin daily, however the study duration was only one week.For paracetamol, no studies were identified for inclusion. AUTHORS' CONCLUSIONS: In the management of rheumatoid arthritis, the concurrent use of NSAIDs with methotrexate appears to be safe provided appropriate monitoring is performed. The use of anti-inflammatory doses of aspirin should be avoided. PMID- 22071859 TI - Antidepressants for pain management in rheumatoid arthritis. AB - BACKGROUND: Pain management is a high priority for patients with rheumatoid arthritis (RA). Antidepressants are sometimes used as adjuvant agents to enhance pain relief, help with sleep and reduce depression. Such antidepressants include tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective serotonin noradrenaline reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). However, the prescription of antidepressants in this population remains controversial because of conflicting scientific evidence. OBJECTIVES: The aim of this review was to determine the efficacy and safety of antidepressants in pain management in patients with RA. SEARCH METHODS: We performed a computer assisted search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, 4th quarter); MEDLINE (1950 to November Week 1, 2010); EMBASE (2010 Week 44); and PsycINFO (1806 to November Week 2, 2010). We also searched the 2008-2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) which compared an antidepressant therapy to another therapy (active or placebo, including non-pharmacological therapies) in adult patients with RA who had at least one clinically relevant outcome measure. Outcomes of interest were pain, adverse effects, function, sleep, depression and quality of life. DATA COLLECTION AND ANALYSIS: Two blinded review authors independently extracted data and assessed the risk of bias in the trials. We conducted meta-analyses to examine the efficacy of antidepressants on pain, depression and function, as well as their safety. MAIN RESULTS: We included eight RCTs (652 participants) in this review. All trials evaluated TCAs and two trials evaluated a SSRI as a comparator. Seven of the eight trials had high risk of bias. There was insufficient data for a number needed to treat for an additional beneficial outcome (NNTB) to be calculated for the primary outcome measure of pain. The qualitative analyses found no evidence of an effect of antidepressants on pain intensity or depression in the short-term (less than one week), and conflicting evidence of a medium- (one to six weeks) or long-term (more than six weeks) benefit. There were significantly more minor adverse events in patients receiving TCAs compared with those receiving a placebo (risk ratio (RR) 2.27, 95% confidence interval (CI) 1.17 to 4.42), but there was no significant increase in withdrawals due to an adverse event (RR 1.09, 95% CI 0.49 to 2.42). AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support the routine prescription of antidepressants as analgesics in patients with RA as no reliable conclusions about their efficacy can be drawn from eight placebo RCTs. The use of these agents may be associated with adverse events which are generally mild and do not lead to cessation of treatment. More high quality trials are needed in this area. PMID- 22071860 TI - Interventions designed to prevent healthcare bed-related injuries in patients. AB - BACKGROUND: Every patient in residential healthcare has a bed. Falling out of bed is associated with preventable patient harm. Various interventions to prevent injury are available. Bed rails are the most common intervention designed to prevent patients falling out of bed; however, their effectiveness is uncertain and bed rail entrapment can also result in injuries. OBJECTIVES: To assess the effectiveness of interventions designed to prevent patient injuries and falls from their beds. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials 2010, Issue 2 (The Cochrane Library), MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), ISOI Web of Science and Web-based trials registers (all to December 2010) as well as reference lists. SELECTION CRITERIA: Randomised controlled trials of interventions designed to prevent patient injuries from their beds which were conducted in hospitals, nursing care facilities or rehabilitation units were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data from the included studies. Authors contacted investigators to obtain missing information. MAIN RESULTS: Two studies met the inclusion criteria, involving a total of 22,106 participants. One study tested low height beds and the other tested bed exit alarms. Both studies used standard care for their control group and both studies were conducted in hospitals. No study investigating bed rails met the inclusion criteria. Due to the clinical heterogeneity of the interventions in the included studies pooling of data and meta-analysis was inappropriate, and so the results of the studies are described.A single cluster randomised trial of low height beds in 18 hospital wards, including 22,036 participants, found no significant reduction in the frequency of patient injuries due to their beds (there were no injuries in either group), patient falls in the bedroom (rate ratio 0.69, 95% CI 0.35 to 1.34), all falls (rate ratio 1.26, 95% CI 0.83 to 1.90) or patient injuries due to all falls (rate ratio 1.35, 95% CI 0.68 to 2.68).One randomised controlled trial of bed exit alarms in one hospital geriatric ward, involving 70 participants, found no significant reduction in the frequency of patient injuries due to their beds (there were no injuries in either group), patient falls out of bed (rate ratio 0.25, 95% CI 0.03 to 2.24), all falls (rate ratio 0.42, 95% CI 0.15 to 1.18) or patient injuries due to all falls (no injuries in either group). AUTHORS' CONCLUSIONS: The effectiveness of interventions designed to prevent patient injuries from their beds (including bed rails, low height beds and bed exit alarms) remains uncertain. The available evidence shows no significant increase or decrease in the rate of injuries with the use of low height beds and bed exit alarms. Limitations of the two included studies include lack of blinding and insufficient power. No randomised controlled trials of bed rails were identified. Future reports should fully describe the standard care received by the control group. PMID- 22071861 TI - Effectiveness of external inspection of compliance with standards in improving healthcare organisation behaviour, healthcare professional behaviour or patient outcomes. AB - BACKGROUND: Inspection systems are used in health care to promote quality improvements, i.e. to achieve changes in organisational structures or processes, healthcare provider behaviour and patient outcomes. These systems are based on the assumption that externally promoted adherence to evidence-based standards (through inspection/assessment) will result in higher quality of health care. However, the benefits of external inspection in terms of organisational, provider and patient level outcomes are not clear. OBJECTIVES: To evaluate the effectiveness of external inspection of compliance with standards in improving healthcare organisation behaviour, healthcare professional behaviour and patient outcomes. SEARCH METHODS: We searched the following electronic databases for studies: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, Scopus, HMIC, Index to Theses and Intute from their inception dates up to May 2011. There was no language restriction and studies were included regardless of publication status. We searched the reference lists of included studies and contacted authors of relevant papers, accreditation bodies and the International Organization for Standardisation (ISO), regarding any further published or unpublished work. SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), interrupted time-series (ITSs) and controlled before and after studies (CBAs) evaluating the effect of external inspection against external standards on healthcare organisation change, healthcare professional behaviour or patient outcomes in hospitals, primary healthcare organisations and other community-based healthcare organisations. DATA COLLECTION AND ANALYSIS: Two review authors independently applied eligibility criteria, extracted data and assessed the risk of bias of each included study. Since meta-analysis was not possible, we produced a narrative results summary. MAIN RESULTS: We identified one cluster-RCT involving 20 South African public hospitals (Salmon 2003) and one ITS involving all acute trusts in England (OPM 2009) for inclusion in this review.Salmon and colleagues (Salmon 2003) showed mixed effects of a hospital accreditation system on the compliance with COHSASA (the Council for Health Services Accreditation for South Africa) accreditation standards and eight indicators of hospital quality. Significantly improved total mean compliance score with COHSASA accreditation standards was found for 21/28 service elements: mean intervention effect (95% confidence interval (CI)) was 30% (23% to 57%) (P < 0.001). The score increased from 48% to 78% in intervention hospitals, while remaining the same in control hospitals (43%). A sub-analysis of 424 a priori identified critical criteria (19 service elements) showed significantly improved compliance with the critical standards (P < 0.001). The score increased from 41% (21% to 46%) to 75% (55% to 96%) in intervention hospitals, but was unchanged in control hospitals (37%). Only one of the nine intervention hospitals gained full accreditation status at the end of the study period, with two others reached pre-accreditation status.The median intervention effect (range) for the indicators of hospital quality of care was 2.4 (-1.9 to +11.8) and only one of the eight indicators: 'nurses perception of clinical quality, participation and teamwork' was significantly improved (mean intervention effect 5.7, P = 0.03).Re-analysis of the MRSA (methicillin-resistant Staphylococcus aureus) data showed statistically non-significant effects of the Healthcare Commissions Infection Inspection programme. AUTHORS' CONCLUSIONS: We only identified two studies for inclusion in this review, which highlights the paucity of high-quality controlled evaluations of the effectiveness of external inspection systems. No firm conclusions could therefore be drawn about the effectiveness of external inspection on compliance with standards. PMID- 22071862 TI - Quadriphasic versus monophasic oral contraceptives for contraception. AB - BACKGROUND: Quadriphasic oral contraceptives have been developed to reduce the adverse effects of oral contraceptives and are presented as more physiological since they mimic the natural cycle. However, suggested disadvantages of quadriphasic oral contraceptives include a possible increased risk of pill-taking errors caused by the array of different color pills, complicated directions for catching up when a pill is missed, the higher price and potential inferiority in terms of side effects. OBJECTIVES: To compare the contraceptive effectiveness, bleeding pattern, minor side effects and acceptability of quadriphasic contraceptive pills versus monophasic contraceptive pills. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov and ICTRP for trials comparing quadriphasic pills with monophasic pills. We contacted researchers and manufacturers of quadriphasic oral contraceptives to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing quadriphasic with monophasic oral contraceptives . Trials had to report on contraceptive effectiveness, bleeding patterns, minor side effects, ease of use or trial discontinuation. We excluded studies where the intervention was primarily used as a treatment for disorders or was administered for fewer than three consecutive cycles. DATA COLLECTION AND ANALYSIS: T wo authors abstracted and entered data into RevMan. We critically appraised the methodological quality of the included trials. For continuous variables, we computed the mean difference with 95% confidence interval (CI) using the random-effects model. For dichotomous variables, we calculated the risk ratio with 95% CI using the random-effects model. MAIN RESULTS: We included one double-blind, double-dummy RCT comparing a quadriphasic oral contraceptive composed of dienogest and estradiol valerate with a monophasic oral contraceptive composed of levonorgestrel and ethinylestradiol. Contraceptive effectiveness, intracyclic bleeding and discontinuation due to side effects were similar for quadriphasic and monophasic pills. The number of women experiencing withdrawal bleeding was higher in the monophasic group compared to the quadriphasic group. Users of quadriphasic pills reported fewer bleeding/spotting days and fewer bleeding/spotting episodes than users of monophasic pills but the report did not specify whether the bleeding/spotting was scheduled or unscheduled. More women using quadriphasic oral contraceptives reported breast pain compared to women using monophasic oral contraceptives. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine whether quadriphasic differ from monophasic oral contraceptives in contraceptive effectiveness, bleeding pattern, minor side effects and acceptability. Studies that compare quadriphasic and monophasic oral contraceptives with an identical progestogen and estrogen type are needed to determine whether the quadriphasic approach differs from the monophasic approach. Studies that compare quadriphasic pills with monophasic pills containing 30 MUg ethinylestradiol are indicated to determine whether quadriphasic oral contraceptives have an advantage over the current, first choice oral contraceptive . Until then, we recommend monophasic pills containing 30 MUg estrogen as the first choice for women starting oral contraceptive use. PMID- 22071863 TI - Neuropsychological rehabilitation for multiple sclerosis. AB - BACKGROUND: Cognitive deficits are a common manifestation in multiple sclerosis (MS) and have a wide effect on the patient's quality of life. Alleviation of the harmful effects caused by these deficits should be a major goal of MS research and practice. OBJECTIVES: The aim of this review was to evaluate the effects of neuropsychological/cognitive rehabilitation in MS by conducting a systematic review. SEARCH METHODS: A systematic literature search was carried out on reports drawn from Cochrane MS Group Specialised Register (To October 2010), Evidence based medicine (EBM) reviews (To September 2010), MEDLINE (January 1950 to September 2010), EMBASE (1974 to September 2010), PsycINFO (January 1806 to September 2010), WEB OF SCIENCE (WOS) (January 1986 to September 2010), CINAHL (1982 to September 2010), and identified from the references in these reports. SELECTION CRITERIA: Randomised Controlled Trials (RCTs) and quasi-randomised trials evaluating the effects of neuropsychological rehabilitation in MS compared to other interventions or no intervention at all and employing neuropsychological rehabilitation methods and outcome measures were included. DATA COLLECTION AND ANALYSIS: Two review authors individually judged the relevance, risk of bias, and content of the included studies. Results were combined quantitatively with meta analyses according to the intervention type: 1) Cognitive training and 2) Cognitive training combined with other neuropsychological rehabilitation methods. In addition, narrative presentation was used in reporting the results of those studies which were inappropriate to be included in the meta-analysis. MAIN RESULTS: Fourteen studies (770 MS patients) fulfilled the inclusion criteria. On the basis of these studies, low level evidence was found that neuropsychological rehabilitation reduces cognitive symptoms in MS. Cognitive training was found to improve memory span (standardised mean difference 0.54 (95% confidence interval 0.2 to 0.88, P = 0.002)), working memory (standardised mean difference 0.33 (95% confidence interval 0.09 to 0.57, P = 0.006)), and immediate visual memory (standardised mean difference 0.32 (95% confidence interval 0.04 to 0.6, P = 0.02)). There was no evidence of an effect of cognitive training combined with other neuropsychological rehabilitation methods on cognitive or emotional functions. The overall quality as well as the comparability of the included studies were relatively low due to methodological limitations and heterogeneity of outcome measures. Although most of the pooled results in the meta-analyses yielded no significant findings, twelve of the fourteen studies showed some evidence of positive effects when the studies were individually analysed. AUTHORS' CONCLUSIONS: The review indicates low level evidence for the positive effects of neuropsychological rehabilitation in MS. Interventions included in the review were heterogeneous. Consequently, clinical inferences can basically be drawn from single studies. Therefore, new trials may change the strength and direction of the evidence. To further strengthen the evidence, well-designed high quality studies are needed. In this systematic review, recommendations are given for improving the quality of future studies on the effects of neuropsychological rehabilitation in MS. PMID- 22071864 TI - Blunt versus sharp suture needles for preventing percutaneous exposure incidents in surgical staff. AB - BACKGROUND: Surgeons and their assistants are especially at risk of exposure to blood due to glove perforations and needle stick injuries during operations. The use of blunt needles can reduce this risk because they don't penetrate skin easily but still perform sufficiently in other tissues. OBJECTIVES: To determine the effectiveness of blunt needles compared to sharp needles for preventing percutaneous exposure incidents among surgical staff. SEARCH METHODS: We searched MEDLINE and EMBASE (until May 2011), CENTRAL, NHSEED, Science Citation Index Expanded, CINAHL, Nioshtic, CISdoc, PsycINFO, and LILACS (until September 2010). SELECTION CRITERIA: Randomised controlled trials (RCTs) of blunt versus sharp suture needles for preventing needle stick injuries among surgical staff measured as glove perforations or self-reported needle stick injuries. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and risk of bias in trials and extracted data. We synthesized study results with a fixed-effect model meta-analysis. MAIN RESULTS: We located 10 RCTs involving 2961 participating surgeons performing an operation in which the use of blunt needles was compared to the use of sharp needles. Four studies focused on abdominal closure, two on caesarean section, two on vaginal repair and two on hip replacement. On average, a surgeon that used sharp needles sustained one glove perforation in three operations. The use of blunt needles reduced the risk of glove perforations with a relative risk (RR) of 0.46 (95% confidence interval (CI) 0.38 to 0.54) compared to sharp needles. The use of blunt needles will thus prevent one glove perforation in every six operations.In four studies, the use of blunt needles reduced the number of self-reported needle stick injuries with a RR of 0.31 (95% CI 0.14 to 0.68). Because the force needed for the blunt needles is higher, their use was rated as more difficult but still acceptable in five out of six studies.The quality of the evidence was rated as high. AUTHORS' CONCLUSIONS: There is high quality evidence that the use of blunt needles appreciably reduces the risk of exposure to blood and bodily fluids for surgeons and their assistants over a range of operations. It is unlikely that future research will change this conclusion. PMID- 22071865 TI - Low molecular weight heparin versus unfractionated heparin for perioperative thromboprophylaxis in patients with cancer. AB - BACKGROUND: The choice of the appropriate perioperative thromboprophylaxis in patients with cancer depends on the relative benefits and harms of low molecular weight heparin (LMWH) and unfractionated heparin (UFH). OBJECTIVES: To systematically review the evidence for the relative efficacy and safety of LMWH and UFH for perioperative thromboprophylaxis in patients with cancer. SEARCH METHODS: A comprehensive search for trials of anticoagulation in cancer patients including a February 2010 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI Web of Science. SELECTION CRITERIA: Randomized controlled trials (RCTs) that enrolled cancer patients undergoing a surgical intervention and compared the effects of LMWH to UFH on mortality, deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding outcomes, and thrombocytopenia. DATA COLLECTION AND ANALYSIS: Two review authors used a standardized form to independently extract in duplicate data on risk of bias, participants, interventions and outcomes of interest. Where possible, we conducted meta-analyses using the random-effects model. MAIN RESULTS: Of 8187 identified citations, we included 16 RCTs with 11,847 patients in the meta analyses, all using preoperative prophylactic anticoagulation. The overall quality of evidence was moderate. The meta-analysis did not conclusively rule out either a beneficial or harmful effect of LMWH compared to UFH for the following outcomes: mortality (RR = 0.90; 95% CI 0.73 to 1.10), symptomatic DVT (RR = 0.73; 95% CI 0.23 to 2.28), PE (RR = 0.59; 95% CI 0.25 to1.41), minor bleeding (RR = 0.88; 95% CI 0.47 to 1.66) and major bleeding (RR = 0.84; 95% CI 0.52 to 1.36). LMWH was associated with lower incidence of wound hematoma (RR = 0.60; 95% CI 0.43, 0.84) while UFH was associated with higher incidence of intra-operative transfusion (RR = 1.16; 95% CI 0.69,1.62). AUTHORS' CONCLUSIONS: We found no difference between perioperative thromboprophylaxis with LMWH verus UFH in their effects on mortality and embolic outcomes in patients with cancer. Further trials are needed to more carefully evaluate the benefits and harms of different heparin thromboprophylaxis strategies in this population. PMID- 22071866 TI - Methods for obtaining unpublished data. AB - BACKGROUND: In order to minimise publication bias, authors of systematic reviews often spend considerable time trying to obtain unpublished data. These include data from studies conducted but not published (unpublished data), as either an abstract or full-text paper, as well as missing data (data available to original researchers but not reported) in published abstracts or full-text publications. The effectiveness of different methods used to obtain unpublished or missing data has not been systematically evaluated. OBJECTIVES: To assess the effects of different methods for obtaining unpublished studies (data) and missing data from studies to be included in systematic reviews. SEARCH METHODS: We identified primary studies comparing different methods of obtaining unpublished studies (data) or missing data by searching the Cochrane Methodology Register (Issue 1, 2010), MEDLINE and EMBASE (1980 to 28 April 2010). We also checked references in relevant reports and contacted researchers who were known or who were thought likely to have carried out relevant studies. We used the Science Citation Index and PubMed 'related articles' feature to identify any additional studies identified by other sources (19 June 2009). SELECTION CRITERIA: Primary studies comparing different methods of obtaining unpublished studies (data) or missing data in the healthcare setting. DATA COLLECTION AND ANALYSIS: The primary outcome measure was the proportion of unpublished studies (data) or missing data obtained, as defined and reported by the authors of the included studies. Two authors independently assessed the search results, extracted data and assessed risk of bias using a standardised data extraction form. We resolved any disagreements by discussion. MAIN RESULTS: Six studies met the inclusion criteria; two were randomised studies and four were observational comparative studies evaluating different methods for obtaining missing data.Methods to obtain missing dataFive studies, two randomised studies and three observational comparative studies, assessed methods for obtaining missing data (i.e. data available to the original researchers but not reported in the published study).Two studies found that correspondence with study authors by e-mail resulted in the greatest response rate with the fewest attempts and shortest time to respond. The difference between the effect of a single request for missing information (by e-mail or surface mail) versus a multistage approach (pre notification, request for missing information and active follow-up) was not significant for response rate and completeness of information retrieved (one study). Requests for clarification of methods (one study) resulted in a greater response than requests for missing data. A well-known signatory had no significant effect on the likelihood of authors responding to a request for unpublished information (one study). One study assessed the number of attempts made to obtain missing data and found that the number of items requested did not influence the probability of response. In addition, multiple attempts using the same methods did not increase the likelihood of response. METHODS TO OBTAIN UNPUBLISHED STUDIES: One observational comparative study assessed methods to obtain unpublished studies (i.e. data for studies that have never been published). Identifying unpublished studies ahead of time and then asking the drug industry to provide further specific detail proved to be more fruitful than sending of a non-specific request. AUTHORS' CONCLUSIONS: Those carrying out systematic reviews should continue to contact authors for missing data, recognising that this might not always be successful, particularly for older studies. Contacting authors by e-mail results in the greatest response rate with the fewest number of attempts and the shortest time to respond. PMID- 22071867 TI - Prognostic value of putative circulating cancer stem cells in patients undergoing hepatic resection for colorectal liver metastasis. AB - BACKGROUND: Although surgery is the gold standard treatment of hepatic metastasis from colorectal cancer (CRC), many patients ultimately die of their disease. We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery. METHODS: We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model. RESULTS: Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9-3.7, P < 0.0001; and hazard ratio 2.1, 95% CI 1.4-3.2, P < 0.0001, respectively]. Remarkably, multivariate analysis found that only the transcriptional amount of CD133 resulted in statistical significance (HR 2.6, 95% CI 1.9-3.6, P < 0.0001), indicating that this biomarker can independently predict the survival of these patients. CONCLUSIONS: CD133-positive CTC may represent a suitable prognostic marker to stratify the risk of patients who undergo liver resection for CRC metastasis, which opens the avenue to identifying and potentially monitoring the patients who are most likely to benefit from adjuvant treatments. PMID- 22071868 TI - Nanoporous palladium with sub-10 nm dendrites by electrodeposition for ethanol and ethylene glycol oxidation. AB - High surface area Pd foams with roughness factors of more than 1000 and a specific surface area of 60 m(2) g(-1) are obtained by electrodeposition. The foams are composed of dendrites with branches on the 10 nm scale. The resulting electrodes show high activity towards the oxidation of C(2) alcohols. PMID- 22071869 TI - Presumptive primary intraocular lymphoma presented as an intraocular mass involving the optic nerve head. PMID- 22071870 TI - Screening for emphysema via exhaled volatile organic compounds. AB - Chronic obstructive pulmonary disease (COPD)/emphysema risk groups are well defined and screening allows for early identification of disease. The capability of exhaled volatile organic compounds (VOCs) to detect emphysema, as found by computed tomography (CT) in current and former heavy smokers participating in a lung cancer screening trial, was investigated. CT scans, pulmonary function tests and breath sample collections were obtained from 204 subjects. Breath samples were analyzed with a proton-transfer reaction mass spectrometer (PTR-MS) to obtain VOC profiles listed as ions at various mass-to-charge ratios (m/z). Using bootstrapped stepwise forward logistic regression, we identified specific breath profiles as a potential tool for the diagnosis of emphysema, of airflow limitation or gas-exchange impairment. A marker for emphysema was found at m/z 87 (tentatively attributed to 2-methylbutanal). The area under the receiver operating characteristic curve (ROC) of this marker to diagnose emphysema was 0.588 (95% CI 0.453-0.662). Mass-to-charge ratios m/z 52 (most likely chloramine) and m/z 135 (alkyl benzene) were linked to obstructive disease and m/z 122 (most probably alkyl homologs) to an impaired diffusion capacity. ROC areas were 0.646 (95% CI 0.562-0.730) and 0.671 (95% CI 0.524-0.710), respectively. In the screening setting, exhaled VOCs measured by PTR-MS constitute weak markers for emphysema, pulmonary obstruction and impaired diffusion capacity. PMID- 22071871 TI - Interleukin-1beta: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. AB - Increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. Here, we show for the first time how IL 1beta, a pro-inflammatory cytokine shown to be increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. IL-1beta was detrimental to neurogenesis, as shown by a decrease in the number of doublecortin positive neuroblasts (-28%), and mature, microtubule-associated protein-2 positive neurons (-36%). Analysis of the enzymes that regulate the kynurenine pathway showed that IL-1beta induced an upregulation of transcripts for indolamine-2,3-dioxygenase (IDO), kynurenine 3-monooxygenase (KMO), and kynureninase (42-, 12- and 30-fold increase, respectively, under differentiating conditions), the enzymes involved in the neurotoxic arm of the kynurenine pathway. Moreover, treatment with IL-1beta resulted in an increase in kynurenine, the catabolic product of IDO-induced tryptophan metabolism. Interestingly, co treatment with the KMO inhibitor Ro 61-8048 reversed the detrimental effects of IL-1beta on neurogenesis. These observations indicate that IL-1beta has a critical role in regulating neurogenesis whereas affecting the availability of tryptophan and the production of enzymes conducive to toxic metabolites. Our results suggest that inhibition of the kynurenine pathway may provide a new therapy to revert inflammatory-induced reduction in neurogenesis. PMID- 22071873 TI - Thinking outside the synapse: pharmacokinetic-based medications for cocaine addiction. PMID- 22071872 TI - Altered learning and Arc-regulated consolidation of learning in striatum by methamphetamine-induced neurotoxicity. AB - Methamphetamine (METH) causes partial depletion of central monoamine systems and cognitive dysfunction in rats and humans. We have previously shown and now further show that the positive correlation between expression of the immediate early gene Arc (activity-regulated, cytoskeleton-associated) in the dorsomedial (DM) striatum and learning on a response reversal task is lost in rats with METH induced striatal dopamine loss, despite normal behavioral performance and unaltered N-methyl-D-aspartate (NMDA) receptor-mediated excitatory post-synaptic currents, suggesting intact excitatory transmission. This discrepancy suggests that METH-pretreated rats may no longer be using the dorsal striatum to solve the reversal task. To test this hypothesis, male Sprague-Dawley rats were pretreated with a neurotoxic regimen of METH or saline. Guide cannulae were surgically implanted bilaterally into the DM striatum. Three weeks after METH treatment, rats were trained on a motor response version of a T-maze task, and then underwent reversal training. Before reversal training, the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5) or an Arc antisense oligonucleotide was infused into the DM striatum. Acute disruption of DM striatal function by infusion of AP5 impaired reversal learning in saline-, but not METH-, pretreated rats. Likewise, acute disruption of Arc, which is implicated in consolidation of long-term memory, disrupted retention of reversal learning 24 h later in saline-, but not METH-, pretreated rats. These results highlight the critical importance of Arc in the striatum in consolidation of basal ganglia mediated learning and suggest that long-term toxicity induced by METH alters the cognitive strategies/neural circuits used to solve tasks normally mediated by dorsal striatal function. PMID- 22071874 TI - [Burnout in anesthesiology and intensive care : is there a problem in Germany?]. AB - BACKGROUND: With the demands faced by anesthetists and intensive care physicians apparently increasing continuously in Germany, the increased risk of burnout in comparison with the general working population is discussed. This debate has previously been merely speculative because of the lack of studies comparing the burn-out risk of the German working population with anesthetists. Accordingly it was not certain whether anesthetists really are at greater risk of developing burnout as has often been suggested. Moreover, age, gender, function, workplace environment, e.g. working at a hospital compared to a general practitioner (GP) surgery, may influence the risk of burnout. Therefore, this study examined whether the risk for anesthetists in Germany suffering from burnout really is greater than in other occupations. In addition, factors influencing the burnout risks of anesthetists were analyzed. METHOD: A total of 3,541 questionnaires completed by German aaesthetists for a study on work satisfaction by the CBI (Copenhagen Burnout Inventory, part of the Copenhagen Psychosocial Questionnaire, COPSOQ) were analyzed. Apart from calculating the number of participants with a high risk of developing burnout syndrome, the data were used to calculate a generalized burnout score for all participants. The score was compared with data from both a random sample representing a wide variety of occupations from among the general population in Germany (n = 4,709) and a random sample of German hospital doctors (n = 616). In addition, subgroups were formed by gender, function (senior consultant, senior physician, specialist, junior doctor) and type and place of work (university hospital, public hospital, private clinic, GP surgery, freelance work) and the proportion of each group with a high risk of burnout syndrome was calculated. In addition, general burnout scores were compared statistically for differences among the various groups. RESULTS: The proportion of study participants with a high risk of burnout was 40.1%. Differences were found to exist between genders (male 37.2% versus female 46%), qualifications (senior consultant 28.9%, senior physician 38%, specialist 41.5%, junior doctor 46.7%) and working in a hospital (41.3%) compared to a GP surgery (33.2%). The random sample of hospital doctors (n = 616) showed a burnout score of 49 +/- 19 (mean +/- standard deviation), compared to 44 +/- 19 for a random sample of the German population (n = 4,709) and 42 +/- 19 for anesthetists (p < 0.01). Of the subgroups formed, the highest score (49.1 +/- 19) was recorded for female junior doctors working in anesthesia. The type of hospital did not influence the burnout score (university hospital 43.8 +/- 19.8 versus public hospital 42.9 +/- 19.1 versus private hospital 42.4 +/- 18.7, p > 0.05). Working in a hospital was found to result in higher burnout scores than in a GP surgery or freelance work (43 +/- 19.2 versus 38.1 +/- 20.5; t(3531) = 5.0, p < 0.001) CONCLUSIONS: Despite 40.1% of anesthetists being at high risk of burnout, generally speaking the risk of burnout among anesthetists was not higher than in other occupational groups in Germany. However, burnout risks for specific groups, such as female junior doctors in anesthesia, were higher and the possibility of providing social support in the workplace should be considered. PMID- 22071875 TI - [Update: studies in intensive care medicine. Results of the last 12 months]. AB - Intensive care medicine plays an important role in the medical care of patients as well as the economic success of hospitals. Knowledge and implementation of recent relevant scientific evidence are prerequisites for high quality care in intensive care medicine. The aim of this review is to present an overview of the most important publications in intensive care medicine published in 2010 and the first half of the year 2011 and to comment on their attributable clinical relevance for intensive care practitioners. In 2010 and up to June 2011 many studies with high patient numbers have been published. The main topics were the treatment of respiratory failure, sepsis and investigations to improve analgosedation. PMID- 22071876 TI - [Outpatient anesthesia for patients with obstructive sleep apnea: results of a national survey]. AB - BACKGROUND: In Germany there is currently no national standard for the management of patients with obstructive sleep apnea syndrome (OSAS). The object of this survey was to obtain information on the treatment concept for patients with OSAS and to report on the current practice in Germany. METHODS: Data collection was obtained through an online questionnaire. A total of 12,113 members of the supporting anesthesia societies from all over Germany were invited to participate via e-mail. Additionally an announcement was made in a professional journal. RESULTS: A total of 1,671 questionnaires were analyzed. The average age of the respondents was 45 years, 64% were male and 36% were female. The average work experience was 16 years and 85% of the respondents were consultants. In total 85% of anesthesiologists were predominantly working in inpatient care and 12% were predominantly active in outpatient care. Of the respondents 63% preferred regional anesthesia, 20% preferred general anesthesia for patients with OSAS and 17% did not have a preference for a specific anesthesia procedure. Outpatient surgery for patients with OSAS was performed by 72% of the respondents using regional anesthesia and by 55% of the respondents using local anesthesia with sedation. Of the anesthesiologists 49% consented to outpatient surgery using general anesthesia and 14% to interventions involving the airways. Compared to anesthesiologists working predominantly in inpatient departments, those working predominantly in outpatient departments treated patients with OSAS more frequently on an outpatient basis, used general anesthesia significantly more often, discharged those patients significantly earlier and observed less complications. CONCLUSIONS: This survey shows that outpatient surgery for patients with sleep apnea is common practice in Germany. It is also performed when patients have moderate or severe OSAS and for respiratory tract surgery. This means that the management is not conform to the guidelines of the American Society of Anesthesiologists (ASA). PMID- 22071877 TI - [Intubation of children with or without relaxants?]. PMID- 22071878 TI - First-order metal-insulator transition and infrared identification of shape controlled magnetite nanocrystals. AB - The first-order metal-insulator transition (MIT) in magnetite has been known for a long time but is still controversial in its nature. In this study, well-defined magnetite nanocrystals (NCs) with controllable size, shape and terminated surface are first employed to elucidate this important issue, and new discoveries such as a highly suppressed phase transition temperature are identified by monitoring the variable-temperature electric resistance and infrared spectroscopy. Significantly, by carefully comparing the infrared vibrational bands of the as prepared magnetite NCs with octahedral and cubic shapes, respectively, we found that these two forms of magnetite NCs exhibited different transmittance changes and frequency shifts of the infrared characteristics, presumably due to the differences in the lattice distortions on the corresponding {001} and {111} terminal surfaces. This result produced evidence in support of the charge ordering of Fe atoms along the low dimensionality at octahedral B sites undergoing the MIT. Taken together, infrared identification was proposed to be an available characterization strategy for MIT, which can reflect more information on the elusive lattice distortion of crystallographic structure or exposed surfaces. PMID- 22071879 TI - DNA testing and domestic dogs. AB - There are currently about 80 different DNA tests available for mutations that are associated with inherited disease in the domestic dog, and as the tools available with which to dissect the canine genome become increasingly sophisticated, this number can be expected to rise dramatically over the next few years. With unrelenting media pressure focused firmly on the health of the purebred domestic dog, veterinarians and dog breeders are turning increasingly to DNA tests to ensure the health of their dogs. It is ultimately the responsibility of the scientists who identify disease-associated genetic variants to make sensible choices about which discoveries are appropriate to develop into commercially available DNA tests for the lay dog breeder, who needs to balance the need to improve the genetic health of their breed with the need to maintain genetic diversity. This review discusses some of the factors that should be considered along the route from mutation discovery to DNA test and some representative examples of DNA tests currently available. PMID- 22071880 TI - A comparative study of prothrombin complex concentrates and fresh-frozen plasma for warfarin reversal under static and flow conditions. AB - Prothrombin complex concentrates (PCCs) and fresh-frozen plasma (FFP) have been clinically used for acute warfarin reversal. The recovery of prothrombin time (PT) or international normalised ratio (INR) is often reported as an endpoint, but haemostatic efficacies of PCCs and FFP may not be fully reflected in static clotting test in platelet-poor plasma. Using various in vitro assays, we compared the effects of two PCC preparations (3-factor PCC; Bebulin and 4-factor PCC; Beriplex) and FFP on warfarin reversal under static and flow conditions. First, we added an aliquot of either PCC (0.3 or 0.72 U/ml) or 20% FFP (v/v) to commercial warfarin plasma (INR 3.2, or 10.3), and then measured PT, factor II, factor VII, and thrombin generation. Subsequently, we collected whole blood samples from six consented warfarin-treated patients with mean INR 3.0 +/- 0.5 (range 2.5-3.7), and compared clot formation under flow conditions at 280 s-1 before and after addition of either PCC preparation (0.3 and 0.6 U/ml) or 20% of FFP (v/v). PT/INR were restored by either PCC in plasma with INR 3.0, but they were more effectively corrected by 4-factor PCC than 3-factor PCC in plasma with INR 10.3. Effects of FFP were similar to 0.3 U/ml of PCCs in terms of PT, but FFP was less efficacious than PCCs in recovering thrombin generation or factor II levels. In flow experiments, the onset of thrombus formation was shortened by either PCC, but not by FFP, contrary to shortened PT values. For warfarin reversal 20% volume replacement with FFP is inferior to PCCs. PMID- 22071882 TI - Placebo-controlled study of the effects of fingolimod on cardiac rate and rhythm and pulmonary function in healthy volunteers. AB - PURPOSE: Fingolimod (FTY720) is a sphingosine-1 phosphate-receptor (S1PR) modulator recently approved as a once-daily oral therapy for relapsing multiple sclerosis (MS) in many countries. As S1PRs are widely expressed, including in heart and lung tissues, this study investigated the possible effects of fingolimod on heart-rate circadian rhythm and pulmonary function. METHODS: Healthy volunteers (n = 39) were randomized to receive fingolimod 0.5 mg, 1.25 mg, or placebo for 14 days. Heart rate and measures of cardiac and pulmonary function were assessed during the study. RESULTS: Mean heart rate for the first 12 h postdose was lower for both fingolimod than for placebo groups (p < 0.001) and remained 10-15 bpm lower than placebo until day 14 (p < 0.05). Heart rate circadian rhythm, cardiac output, stroke volume, and systemic vascular resistance were similar among treatment groups throughout the study. There was no evidence of an effect of fingolimod on pulmonary function. Absolute lymphocyte counts decreased by approximately 70% from baseline in both fingolimod groups (day 14) and began to increase within 14 days of stopping treatment. CONCLUSIONS: In healthy volunteers treated for 14 days, once-daily fingolimod doses of 0.5 mg and 1.25 mg had no effect on cardiac or pulmonary function beyond a transient decrease in heart rate at treatment initiation. PMID- 22071881 TI - Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers. AB - OBJECTIVE: Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. METHODS: Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. RESULTS: Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 +/- 0.11 vs. 0.08 +/- 0.50 mg-1 Mann Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. CONCLUSIONS: The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore unlikely that its use would be of clinical importance. PMID- 22071884 TI - Endocrine disruptor & nutritional effects of heavy metals in ovarian hyperstimulation. AB - PURPOSE: There is increasing concern that environmental chemicals have a direct effect on fertility. Heavy metals such as mercury have been shown to affect various organ systems in humans including nervous system and skin, however they could also act as endocrine disrupting chemicals adversely affecting fertility. Metals such as zinc and selenium are essential micronutrients with diverse functions that may be important for reproductive outcomes. We measured mercury, zinc and selenium levels in the hair, a reliable reflection of long term environmental exposure and dietary status, to correlate with the outcome of ovarian hyperstimulation for in vitro fertilisation (IVF) treatment. METHODS: We analysed the hair of 30 subfertile women for mercury, zinc and selenium using inductively coupled mass spectrometry. Each woman underwent one cycle of IVF treatment. Correlation between the levels of these trace metals and treatment outcomes was investigated. RESULTS: Thirty women were recruited with mean (+/-SD) age of 32.7(4.4) years and BMI of 25.4(5.0)kg/m(2). Hair mercury concentration showed a negative correlation with oocyte yield (p < 0.05,betacoefficient 0.38) and follicle number (p = 0.03,beta coefficient0.19) after ovarian stimulation. Zinc and selenium levels in hair correlated positively with oocyte yield after ovarian stimulation (p < 0.05,beta coefficient0.15) and (p = 0.03,beta coefficient0.21) respectively. Selenium levels in hair correlated significantly with follicle number following stimulation (p = 0.04, betacoefficient0.22). There was no correlation between mercury, zinc and selenium in hair and their corresponding serum levels. CONCLUSION: These data suggest that mercury had a deleterious effect whilst there was a positive effect for zinc and selenium in the ovarian response to gonadotrophin therapy for IVF. Hair analysis offers a novel method of investigating the impact of long-term exposure to endocrine disruptors and nutritional status on reproductive outcomes. PMID- 22071885 TI - Xq;autosome translocation in POF: Xq27.2 deletion resulting in haploinsufficiency for SPANX. PMID- 22071886 TI - Distorted cubic tetranuclear vanadium(IV) phosphonate cages: double-four-ring (D4R) containing transition metal ion phosphonate cages. AB - The reaction of VCl(3) with 3,5-dimethylpyrazole (3,5-Me(2)PzH) and trichloromethylphosphonic/tert-butylphosphonic acid in the presence of triethylamine as a hydrogen chloride scavenger afforded the tetranuclear V(IV) assemblies, [(VO)(4)(3,5-Me(2)PzH)(8)(CCl(3)PO(3))(4)] (1) and [(VO)(4)(3,5 Me(2)PzH)(4)(t-BuPO(3))(4)] (2). Both of these compounds possess a distorted cubic framework structures containing V(IV) ions and phosphorus atoms in the alternate corners of the cube. The edges of the cube contain oxygen atoms derived from the phosphonate ligand. The phosphonate ligand in both of these compounds is dianionic and helps to bind to three V(IV) centers. The faces of the cubic ensembles contain puckered V(2)P(2)O(4) eight-membered rings. The V(IV) center in 1 is six-coordinate in a distorted octahedral geometry while in 2 it is five coordinate in a distorted square-pyramidal geometry. Magnetic studies carried out on 1 and 2 reveal that the V(IV) centers are anti-ferromagnetically coupled to each other, albeit weakly, through the mediation of the phosphonate ligands. PMID- 22071887 TI - Copy number detection in discordant monozygotic twins of Congenital Diaphragmatic Hernia (CDH) and Esophageal Atresia (EA) cohorts. AB - The occurrence of phenotypic differences between monozygotic (MZ) twins is commonly attributed to environmental factors, assuming that MZ twins have a complete identical genetic make-up. Yet, recently several lines of evidence showed that both genetic and epigenetic factors could have a role in phenotypic discordance after all. A high occurrence of copy number variation (CNV) differences was observed within MZ twin pairs discordant for Parkinson's disease, thereby stressing on the importance of post-zygotic mutations as disease predisposing events. In this study, the prevalence of discrepant CNVs was analyzed in discordant MZ twins of the Esophageal Atresia (EA) and Congenital Diaphragmatic Hernia (CDH) cohort in the Netherlands. Blood-derived DNA from 11 pairs (7 EA and 4 CDH) was screened using high-resolution SNP arrays. Results showed an identical copy number profile in each twin pair. Mosaic chromosome gain or losses could not be detected either with a detection threshold of 20%. Some of the germ-line structural events demonstrated in five out of eleven twin pairs could function as a susceptible genetic background. For example, the 177-Kb loss of chromosome 10q26 in CDH pair-3 harbors the TCF7L2 gene (Tcf4 protein), which is implicated in the regulation of muscle fiber type development and maturation. In conclusion, discrepant CNVs are not a common cause of twin discordancy in these investigated congenital anomaly cohorts. PMID- 22071888 TI - Health-care providers' views on pursuing reproductive benefit through newborn screening: the case of sickle cell disorders. AB - Newborn screening (NBS) programs aim to identify affected infants before the onset of treatable disorders. Historically, benefits to the family and society were considered secondary to this clinical benefit; yet, recent discourse defending expanded NBS has argued that screening can in part be justified by secondary benefits, such as learning reproductive risk information to support family planning ('reproductive benefit'). Despite increased attention to these secondary benefits of NBS, stakeholders' values remain unknown. We report a mixed methods study that included an examination of providers' views toward the pursuit of reproductive risk information through NBS, using sickle cell disorder carrier status as an example. We surveyed a stratified random sample of 1615 providers in Ontario, and interviewed 42 providers across 7 disciplines. A majority endorsed the identification of reproductive risks as a goal of NBS (74-77%). Providers' dominant rationale was that knowledge of carrier status is an important and inherent benefit of NBS as it allows people to make reproductive choices, which is consistent with the goals of disease prevention. However, some challenged its appropriateness, questioning its logic, timing and impact on disease prevention. Others were sensitive to intruding on individuals' choices or children's independent rights. While the dominant view is consistent with discourse defending expanded NBS, it deviates from the traditional screening principles that underpin most public health interventions. Broader discussion of the balance between benefits to screened individuals and those to families and societies, in the context of public health programs, is needed. PMID- 22071889 TI - Underexpression and abnormal localization of ATM products in ataxia telangiectasia patients bearing ATM missense mutations. AB - Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, immune defects and predisposition to malignancies. A-T is caused by biallelic inactivation of the ATM gene, in most cases by frameshift or nonsense mutations. More rarely, ATM missense mutations with unknown consequences on ATM function are found, making definitive diagnosis more challenging. In this study, a series of 15 missense mutations, including 11 not previously reported, were identified in 16 patients with clinical diagnosis of A-T belonging to 14 families and 1 patient with atypical clinical features. ATM function was evaluated in patient lymphoblastoid cell lines by measuring H2AX and KAP1 phosphorylation in response to ionizing radiation, confirming the A-T diagnosis for 16 cases. In accordance with previous studies, we showed that missense mutations associated with A-T often lead to ATM protein underexpression (15 out of 16 cases). In addition, we demonstrated that most missense mutations lead to an abnormal cytoplasmic localization of ATM, correlated with its decreased expression. This new finding highlights ATM mislocalization as a new mechanism of ATM dysfunction, which may lead to therapeutic strategies for missense mutation associated A-T. PMID- 22071890 TI - ALK germline mutations in patients with neuroblastoma: a rare and weakly penetrant syndrome. AB - Neuroblastic tumours may occur in a predisposition context. Two main genes are involved: PHOX2B, observed in familial cases and frequently associated with other neurocristopathies (Ondine's and Hirschsprung's disease); and ALK, mostly in familial tumours. We have assessed the frequency of mutations of these two genes in patients with a presumable higher risk of predisposition. We sequenced both genes in 26 perinatal cases (prebirth and <1 month of age, among which 10 were multifocal), 16 multifocal postnatal (>1 month) cases, 3 pairs of affected relatives and 8 patients with multiple malignancies. The whole coding sequences of the two genes were analysed in tumour and/or constitutional DNAs. We found three ALK germline mutations, all in a context of multifocal tumours. Two mutations (T1151R and R1192P) were inherited and shared by several unaffected patients, thus illustrating an incomplete penetrance. Younger age at tumour onset did not seem to offer a relevant selection criterion for ALK analyses. Conversely, multifocal tumours might be the most to benefit from the genetic screening. Finally, no PHOX2B germline mutation was found in this series. In conclusion, ALK deleterious mutations are rare events in patients with a high probability of predisposition. Other predisposing genes remain to be discovered. PMID- 22071891 TI - A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development. AB - Disorders of sex development (DSD) are congenital conditions where chromosomal, gonad or genital development is atypical. In a significant proportion of 46,XY DSD cases it is not possible to identify a causative mutation, making genetic counseling difficult and potentially hindering optimal treatment. Here, we describe the analysis of a 46,XY DSD patient that presented at birth with ambiguous genitalia. Histological analysis of the surgically removed gonads showed bilateral undifferentiated gonadal tissue and immature testis, both containing malignant germ cells. We screened genomic DNA from this patient for deletions and duplications using an Illumina whole-genome SNP microarray. This analysis revealed a heterozygous deletion within the WWOX gene on chromosome 16, removing exons 6-8. Analysis of parental DNA showed that the deletion was inherited from the mother. cDNA analysis confirmed that the deletion maintained the reading frame, with exon 5 being spliced directly onto exon 9. This deletion is the first description of a germline rearrangement affecting the coding sequence of WWOX in humans. Previously described Wwox knockout mouse models showed gonadal abnormalities, supporting a role for WWOX in human gonad development. PMID- 22071892 TI - Newborn screening for sickle cell disease: whose reproductive benefit? PMID- 22071894 TI - Clinical utility gene card for: adrenoleukodystrophy. PMID- 22071893 TI - Preimplantation genetic diagnosis in female and male carriers of reciprocal translocations: clinical outcome until delivery of 312 cycles. AB - Carriers of reciprocal translocations (rcp) are known to be at risk for reproductive difficulties. Preimplantation genetic diagnosis (PGD) is one of the options these carriers have to try in order to fulfil their desire to have a child. In the present study, we retrospectively looked at the results of 11 years (1997-2007) of PGD for rcp in our center to improve the reproductive counseling of these carriers. During this period 312 cycles were performed for 69 male and 73 female carriers. The mean female age was 32.8 years, the mean male age 35.8 years. Most carriers were diagnosed with a translocation because of fertility problems or recurrent miscarriages, and most of them opted for PGD to avoid these problems. In 150 of the 312 cycles, embryo transfer (ET) was feasible and 40 women had a successful singleton or twin pregnancy. This gives a live birth delivery rate of 12.8% per started cycle and of 26.7% per cycle with ET. Owing to the large number of abnormal embryos, PGD cycles for rcp often lead to cancellation of ET, explaining the low success rate when expressed per cycle with oocyte pick-up. Once ET was feasible, the live birth delivery rate was similar to that of PGD in general at our center. PGD is therefore an established option for specific reciprocal translocation carriers. PMID- 22071895 TI - Identification of the first PAR1 deletion encompassing upstream SHOX enhancers in a family with idiopathic short stature. AB - Short stature homeobox-containing gene, MIM 312865 (SHOX) is located within the pseudoautosomal region 1 (PAR1) of the sex chromosomes. Mutations in SHOX or its downstream transcriptional regulatory elements represent the underlying molecular defect in ~60% of Leri-Weill dyschondrosteosis (LWD) and ~5-15% of idiopathic short stature (ISS) patients. Recently, three novel enhancer elements have been identified upstream of SHOX but to date, no PAR1 deletions upstream of SHOX have been observed that only encompass these enhancers in LWD or ISS patients. We set out to search for genetic alterations of the upstream SHOX regulatory elements in 63 LWD and 100 ISS patients with no known alteration in SHOX or the downstream enhancer regions using a specifically designed MLPA assay, which covers the PAR1 upstream of SHOX. An upstream SHOX deletion was identified in an ISS proband and her affected father. The deletion was confirmed and delimited by array-CGH, to extend ~286 kb. The deletion included two of the upstream SHOX enhancers without affecting SHOX. The 13.3-year-old proband had proportionate short stature with normal GH and IGF-I levels. In conclusion, we have identified the first PAR1 deletion encompassing only the upstream SHOX transcription regulatory elements in a family with ISS. The loss of these elements may result in SHOX haploinsufficiency because of decreased SHOX transcription. Therefore, this upstream region should be included in the routine analysis of PAR1 in patients with LWD, LMD and ISS. PMID- 22071896 TI - Preimplantation genetic diagnosis (PGD) for Huntington's disease: the experience of three European centres. AB - This study provides an overview of 13 years of experience of preimplantation genetic diagnosis (PGD) for Huntington's disease (HD) at three European PGD centres in Brussels, Maastricht and Strasbourg. Information on all 331 PGD intakes for HD, couples' reproductive history, PGD approach, treatment cycles and outcomes between 1995 and 2008 were collected prospectively. Of 331 couples for intake, 68% requested direct testing and 32% exclusion testing (with a preponderance of French couples). At the time of PGD intake, 39% of women had experienced one or more pregnancies. A history of pregnancy termination after prenatal diagnosis was observed more frequently in the direct testing group (25%) than in the exclusion group (10%; P=0.0027). PGD workup was based on two approaches: (1) direct testing of the CAG-triplet repeat and (2) linkage analysis using intragenic or flanking microsatellite markers of the HTT gene. In total, 257 couples had started workup and 174 couples (70% direct testing, 30% exclusion testing) completed at least one PGD cycle. In total, 389 cycles continued to oocyte retrieval (OR). The delivery rates per OR were 19.8%, and per embryo transfer 24.8%, resulting in 77 deliveries and the birth of 90 children. We conclude that PGD is a valuable and safe reproductive option for HD carriers and couples at risk of transmitting HD. PMID- 22071897 TI - Variations in maternal behavior--oxytocin and reward pathways--peripheral measures matter?! PMID- 22071908 TI - SCH58261 the selective adenosine A(2A) receptor blocker modulates ischemia reperfusion injury following bilateral carotid occlusion: role of inflammatory mediators. AB - In the present study, the effects of SCH58261, a selective adenosine A(2A) receptor antagonist that crosses the blood brain barrier (BBB) and 8-(4 sulfophenyl) theophylline (8-SPT), a non-selective adenosine receptor antagonist that acts peripherally, were investigated on cerebral ischemia reperfusion injury (IR). Male Wistar rats (200-250 g) were divided into four groups: (1) sham operated (SO), IR pretreated with either (2) vehicle (DMSO); (3) SCH58261 (0.01 mg/kg); (4) 8-SPT (2.5 mg/kg). Animals were anesthetized and submitted to occlusion of both carotid arteries for 45 min. All treatments were administered intraperitoneally (i.p.) post carotid occlusion prior to exposure to a 24 h reperfusion period. Ischemic rats showed increased infarct size compared to their control counterparts that corroborated with histopathological changes as well as increased lactate dehydrogenase (LDH) activity in the hippocampus. Moreover, ischemic animals showed habituation deficit, increased anxiety and locomotor activity. IR increased hippocampal glutamate (Glu), GABA, glycine (Gly) and aspartate (ASP). SCH58261 significantly reversed these effects while 8-SPT elicited minimal change. IR raised myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha), nitric oxide (NO), prostaglandin E2 (PGE2) accompanied by a decrease in interleukin-10 (IL-10), effects that were again reversed by SCH58261, but 8-SPT elicited less changes. Results from the present study point towards the importance of central blockade of adenosine A(2A) receptor in ameliorating hippocampal damage following IR injury by halting inflammatory cascades as well as modulating excitotoxicity. PMID- 22071909 TI - 6-Hydroxyindole-based borondipyrromethene: synthesis and spectroscopic studies. AB - A 6-hydroxyindole-based BODIPY, named BODIPY-OH, with distinct spectroscopic characteristics is reported. Through a systematic study of the spectroscopic characteristics of BODIPY-OH and BODIPY-O(-) in various solvents containing an organic base, we found that the light-color of the fluorophore can be tuned over a wide range by changing the polarity of solvent/base combinations. The absorption color of the solution can be tuned over a range of 100 nm and the emission color within a wide range from 571 to 681 nm by simply converting the phenol form of BODIPY-OH to the phenolate form. Fluorescence of BODIPY-O(-) with high quantum yield shows relatively large Stokes shift in solvent/base combinations, which are ascribed to the excited state deprotonation from (BODIPY OH)* to (BODIPY-O(-))*, followed by emission from the ion form. PMID- 22071910 TI - Yersinia enterocolitica strains associated with human infections in Switzerland 2001-2010. AB - Yersinia enterocolitica infections are common in humans. However, very scarce data are available on the different biotypes and virulence factors of human strains, which has proved to be problematic to assess the clinical significance of the isolated strains. In this study, the presence of the ail gene and distribution of different bio- and serotypes among human Y. enterocolitica strains and their possible relation to the genotype and antimicrobial resistance were studied. In total, 128 Y. enterocolitica strains isolated from human clinical samples in Switzerland during 2001-2010 were characterised. Most (75 out of 128) of the Y. enterocolitica strains belonged to biotypes 2, 3 or 4 and carried the ail gene. One of the 51 strains that belonged to biotype 1A was also ail positive. Most of the ail-positive strains belonged to bioserotype 4/O:3 (47 out of 76) followed by 2/O:9 (22 out of 76). Strains of bioserotype 4/O:3 were dominant among patients between 20 and 40 years old and strains of biotype 1A dominate in patients over 40 years. Strains belonging to biotypes 2, 3 and 4, which all carried the ail gene, exhibited a high homogeneity with PFGE typing. Y. enterocolitica 2/O:5,27 and 2/O:9 strains showed resistance to amoxicillin/clavulanic acid and cefoxitin, but Y. enterocolitica 4/O:3 strains did not. PMID- 22071911 TI - The general environment fit scale: a factor analysis and test of convergent construct validity. AB - Person-environment fit (P-E fit) was initially espoused as an important construct in the field of community psychology; however, most of the theoretical and empirical development of the construct has been conducted by the industrial/organizational (I/O) psychologists and business management fields. In the current study, the GEFS-a P-E fit measure that was developed from organizational perspectives on fit-was administered to 246 attendees of an annual convention for residents and alumni of Oxford House, a network of over 1,400 mutual-help addiction recovery homes. The authors conducted confirmatory factor and convergent construct validity analyses with the GEFS. The results suggested that the theoretical factor structure of the measure adequately fit the data and provided limited support for the measure's validity. Sufficient supply of resident needs by the Oxford House and similarity between residents and their housemates predicted satisfaction with the recovery home, but only perceived similarity to housemates predicted how long residents intended to stay in the Oxford Houses. PMID- 22071912 TI - [Therapeutic management of malaria]. AB - Plasmodium falciparum and to some extent malaria caused by other species of Plasmodia can quickly lead to cerebral malaria, acute renal failure, or acute respiratory distress syndrome. The mortality rate for patients with severe malaria lies around 10%. Malaria must be given priority in the differential diagnosis of travelers returning febrile from endemic areas. Treatment requires prompt administration of safe and fast-acting antimalarials, which in severe malaria is treatment with quinine or artesunate. Hospitals must be prepared to diagnose and treat malaria patients-or have a standard operating procedure for transferring the patient to a specialized center. PMID- 22071913 TI - [Current treatment options in acute myeloid leukemia]. AB - Genetic aberrations form the basis for diagnostic classification of patients with acute myeloid leukemia (AML) according to the World Health Organization (WHO) classification. Moreover, these aberrations predict response to induction chemotherapy, relapse-free survival, and overall survival of patients with AML. Understanding the pathogenetic role of cytogenetic and molecular changes has led to the development of targeted treatment strategies that require rapid diagnostic assessment of the genetic profile of each patient to select the best treatment available. PMID- 22071914 TI - Optimal positioning for emergent needle thoracostomy: a cadaver-based study. AB - BACKGROUND: Needle thoracostomy is an emergent procedure designed to relieve tension pneumothorax. High failure rates because of the needle not penetrating into the thoracic cavity have been reported. Advanced Trauma Life Support guidelines recommend placement in the second intercostal space, midclavicular line using a 5-cm needle. The purpose of this study was to evaluate placement in the fifth intercostal space, midaxillary line, where tube thoracostomy is routinely performed. We hypothesized that this would result in a higher successful placement rate. METHODS: Twenty randomly selected unpreserved adult cadavers were evaluated. A standard 14-gauge 5-cm needle was placed in both the fifth intercostal space at the midaxillary line and the traditional second intercostal space at the midclavicular line in both the right and left chest walls. The needles were secured and thoracotomy was then performed to assess penetration into the pleural cavity. The right and left sides were analyzed separately acting as their own controls for a total of 80 needles inserted into 20 cadavers. The thickness of the chest wall at the site of penetration was then measured for each entry position. RESULTS: A total of 14 male and 6 female cadavers were studied. Overall, 100% (40 of 40) of needles placed in the fifth intercostal space and 57.5% (23 of 40) of the needles placed in the second intercostal space entered the chest cavity (p < 0.001); right chest: 100% versus 60.0% (p = 0.003) and left chest: 100% versus 55.0% (p = 0.001). Overall, the thickness of the chest wall was 3.5 cm +/- 0.9 cm at the fifth intercostal space and 4.5 cm +/- 1.1 cm at the second intercostal space (p < 0.001). Both right and left chest wall thicknesses were similar (right, 3.6 cm +/- 1.0 cm vs. 4.5 cm +/- 1.1 cm, p = 0.007; left, 3.5 +/- 0.9 cm vs. 4.4 cm +/- 1.1 cm, p = 0.008). CONCLUSIONS: In a cadaveric model, needle thoracostomy was successfully placed in 100% of attempts at the fifth intercostal space but in only 58% at the traditional second intercostal position. On average, the chest wall was 1 cm thinner at this position and may improve successful needle placement. Live patient validation of these results is warranted. PMID- 22071915 TI - Two-year experience of using pigtail catheters to treat traumatic pneumothorax: a changing trend. AB - BACKGROUND: The traditional treatment of patients with traumatic hemopneumothorax has been an insertion of a chest tube (CT). But CT, because of its large caliber and significant trauma during an insertion, can cause pain, prevent full lung expansion, and worsen pulmonary outcome. Pigtail catheters (PCs) are smaller and less invasive; they have worked well in patients with nontraumatic pneumothorax (PTX). The purpose of this study was to review our early experience of PC use in trauma patients. METHODS: We retrospectively reviewed the charts of trauma patients who required CT or PC placement over a 2-year period (January 2008 through December 2009) at a Level I trauma center. The PCs were 14-French (14-F) Cook catheters placed by the trauma team, using a Seldinger technique. We compared outcome for the subgroups that had CT or PC placed for a PTX. For our statistical analysis, we used the unpaired Student t-test, chi(2) test, and Wilcoxon rank-sum test; we considered a p value < 0.05 as significant. RESULTS: Of 9,624 trauma patients evaluated, 94 were treated with PC and 386 with CT. Of the PC patients, 89% was inserted for PTX. When comparing patients with PC and CT inserted for PTX, demographics, tube days, need for mechanical ventilation, and insertion-related complications were similar. The tube failure rate, defined by a requirement for an additional tube or by recurrence that needed intervention, was higher in PC (11%) than in CT (4%) (p = 0.06), but the difference was not statistically significant. We observed a trend of increased PC use over time. CONCLUSION: PC is safe and can be performed at the bedside. It has a comparable efficacy to CT in patients with PTX. A prospective study is needed to determine the precise role of PC placement, including its indication, the associated tube site pain, and any significant clinical advantages. PMID- 22071916 TI - Finding the sweet spot: identification of optimal glucose levels in critically injured patients. AB - BACKGROUND: Conflicting data exist regarding optimal glycemic control in critically ill trauma patients. We therefore compared glucose parameters and outcomes among three different glycemic control regimens in a single trauma intensive care unit (ICU), hypothesizing that a moderate regimen would yield optimal avoidance of hyper- and hypoglycemia with equivalent outcomes when compared with a more aggressive approach. METHODS: We retrospectively reviewed 1,422 trauma patients with at least 3-day ICU stay and five glucose measurements from May 2001 to January 2010, spanning three nonoverlapping, sequential glucose control protocols: "relaxed," "aggressive," and "moderate." For each, we extracted mean blood glucose, hypoglycemic and hyperglycemic event frequency, and glucose variability and investigated their association with outcomes. RESULTS: Mortality was associated with elevated mean glucose (135.6 mg/dL vs. 126.2 mg/dL), more frequent hypoglycemic (2.67 +/- 7 vs. 1.28 +/- 5) and hyperglycemic (30.6 +/- 28 vs. 16.0 +/- 22 per 100 patient-ICU days) events, and higher glucose variability (37.1 +/- 20 vs. 29.4 +/- 20; all p < 0.001). Regression identified hyperglycemic episodes (p < 0.05) as an independent predictor of mortality. The "moderate" regimen had rare hyperglycemia, low glucose variability, and intermediate mean blood glucose range and frequency of hypoglycemia. Multiorgan failure and mortality did not differ between groups. CONCLUSIONS: Hyperglycemic events (glucose >180 mg/dL) most strongly predicted mortality. Of glucose control protocols analyzed, the "moderate" protocol had fewest hyperglycemic events. As outcomes were otherwise equivalent between "moderate" and "aggressive" protocols, we conclude that hyperglycemia can be safely avoided using a moderate glycemic control protocol without inducing hypoglycemia. PMID- 22071917 TI - Aged plasma transfusion increases mortality in a rat model of uncontrolled hemorrhage. AB - INTRODUCTION: Recent data have associated improved survival after hemorrhagic shock with the early use of plasma-based resuscitation. Our laboratory has shown that FFP5 has decreased hemostatic potential compared with freshly thawed plasma (FFP0). We hypothesized that FFP5 would increase bleeding and mortality compared with FFP0 in a rodent bioassay model of uncontrolled liver hemorrhage. METHODS: Hemostatic potential of plasma was assessed with the Calibrated Automated Thrombogram (CAT) assay. Rats underwent isovolemic hemodilution by 15% of blood volume with the two human plasma groups (FFP0 and FFP5) and two controls (sham and lactated Ringers). A liver injury was created by excising a portion of liver resulting in uncontrolled hemorrhage. Rats that lived for 30 minutes after liver injury were resuscitated to their baseline blood pressure and followed for 6 hours. Hemostasis was assessed by thromboelastography. RESULTS: Hemostatic potential of FFP5 decreased significantly in all areas measured in the CAT assay as compared with FFP0 (p < 0.01). In the FFP5 group, overall survival was 54%, compared with 100% in the FFP0 and sham group (p = 0.03). For animals that survived 30 minutes and were resuscitated, there was no difference in bleeding and/or coagulopathy between groups. Irrespective of treatment, animals that died after resuscitation demonstrated increased intraperitoneal fluid volume (14.85 mL +/- 1.9 mL vs. 7.02 mL +/- 0.3 mL, p < 0.001). CONCLUSION: In this model of mild preinjury hemodilution with plasma, rats that received FFP5 had decreased survival after uncontrolled hemorrhage from hepatic injury. There were no differences in coagulation function or intraperitoneal fluid volume between the two plasma groups. PMID- 22071918 TI - An assessment of patient satisfaction with nonoperative management of clavicular fractures using the disabilities of the arm, shoulder and hand outcome measure. AB - BACKGROUND: Clavicle fractures historically have been managed without internal fixation. Current literature is raising questions regarding this management as opposed to offering operative fixation in some instances. This study addresses the use of the Disabilities of the Arm, Shoulder and Hand (DASH) outcomes measure to identify those that have the least satisfaction with nonoperative care of the clavicle fracture based upon clavicular deformity and variation in fracture location based upon Allman Classification. METHODS: Patients having suffered clavicle fractures were mailed the DASH Outcomes Questionnaire to be completed and returned. A total of 113 surveys were returned completed with 92 being of value for evaluation. Patient chest or clavicle radiographs were evaluated, and measurements were made of the clavicle fractures for amount of separation or shortening and grade according to Allman Classification. Statistical evaluation compared DASH Scores (patient satisfaction as outcome measure) to the Allman Classification and the degree of separation or shortening. Comparison of categorical variables was performed using Fisher's exact test. Comparison of continuous variables was preformed using Student's t test. Statistical significance was demonstrated by a p value of less than 0.05. RESULTS: Patients with clavicular shortening of greater than 2 cm were found to have the highest DASH score indicating dissatisfaction and disability with their outcome postinjury (p = 0.0001). Separation or lengthening seemed to be associated with lower DASH Scores. Patients with Allmen Classification I (midshaft clavicle) fractures had higher DASH score than other fracture locations (p = 0.0001). CONCLUSIONS: Patients with midshaft clavicle fractures with shortening of greater than 2 cm may be good candidates for operative repair given the degree of dissatisfaction with nonoperative management of these fractures as assessed by long-term outcome measures of disability. PMID- 22071919 TI - Je le pansay ... (I bound his wound ...). PMID- 22071920 TI - Cardiac changes after simulated behind armor blunt trauma or impact of nonlethal kinetic projectile ammunition. AB - BACKGROUND: Cardiac-related injuries caused by blunt chest trauma remain a severe problem. The aim of this study was to investigate pathophysiological changes in the heart that might arise after behind armor blunt trauma or impacts of nonlethal projectiles. METHODS: Sixteen pigs were shot directly at the sternum with "Sponge Round eXact I Mpact" (nonlethal ammunition; diameter 40 mm and weight 28 g) or hard-plastic ammunition (diameter 65 mm and weight 58 g) to simulate behind armor blunt trauma. To evaluate the influence of the shot location, seven additional pigs where exposed to an oblique heart shot. Physiologic parameters, electrocardiography, echocardiogram, the biochemical marker troponin I (TnI), and myocardial injuries were analyzed. RESULTS: Nonlethal kinetic projectiles (101-108 m/s; 143-163 J) did not cause significant pathophysiological changes. Five of 18 pigs shot with 65-mm plastic projectiles (99-133 m/s; 284-513 J) to the front or side of the thorax died directly after the shot. No major physiologic changes could be observed in surviving animals. Animals shot with an oblique heart shot (99-106 m/s; 284-326 J) demonstrated a small, but significant decrease in saturation. Energy levels over 300 J caused increased TnI and myocardial damages in most of the pigs. CONCLUSION: This study indicates that nonlethal kinetic projectiles "eXact iMpact" does not cause heart related damage under the examined conditions. On impact, sudden heart arrest may occur independently from the cardiac's electrical cycle. The cardiac enzyme, TnI, can be used as a reliable diagnostic marker to detect heart tissue damages after blunt chest trauma. PMID- 22071921 TI - Blood component ratios in massively transfused, blunt trauma patients--a time dependent covariate analysis. AB - BACKGROUND: This study evaluated critical thresholds for fresh frozen plasma (FFP) and platelet (PLT) to packed red blood cell (PRBC) ratios and determined the impact of high FFP:PRBC and PLT:PRBC ratios on outcomes in patients requiring massive transfusion (MT). METHODS: Retrospective review of a cohort of massively transfused blunt trauma patients admitted to a Level I trauma center. MT was defined as transfusion of >=10 units of PRBC within 24 hours of admission. Critical thresholds for FFP:PRBC and PLT:PRBC ratios associated with mortality were identified using Cox regression with time-dependent variables. Impacts of high blood component ratios on 12-hour and 24-hour survival were evaluated. RESULTS: During the 10-year study period, a total of 229 blunt trauma patients required a MT. At 12 hours and 24 hours after admission, a FFP:PRBC ratio threshold of 1:1.5 was found to have the strongest association with mortality. At 12 hours, 58 patients (25.4%) received a low (<1:1.5) and 171 patients (74.6%) a high (>=1:1.5) FFP:PRBC ratio. Patients in the low ratio group had a significantly higher mortality compared with those in the high ratio group (51.7% vs. 9.4%; adjusted hazard ratio [95% confidence interval] = 1.18 [1.04-1.34]; adjusted p = 0.008). A similar statistically significant difference was found at 24 hours after admission. For PLTs, a PLT:PRBC ratio of 1:3 was identified as the best cut-off associated with both 12-hour and 24-hour survival. At 12 hours, 79 patients (34.5%) received a low (<1:3) and 150 patients (65.5%) a high (>=1:3) PLT:PRBC ratio. After adjusting for differences between the ratio groups, no statistically significant survival advantage associated with a high PLT:PRBC ratio was found (40.5% vs. 9.3%; adjusted hazard ratio [95% confidence interval] = 1.11 [0.99-1.26]; adjusted p = 0.082). CONCLUSION: For massively transfused blunt trauma patients, a plasma to PRBC ratio of >=1:1.5 was associated with improved survival at 12 hours and 24 hours after hospital admission. However, for PLTs, no statistically significant survival benefit with increasing ratio was observed. The results of this analysis highlight the need for prospective studies to evaluate the clinical significance of high blood component ratios on outcome. PMID- 22071922 TI - Using the abbreviated injury severity and Glasgow Coma Scale scores to predict 2 week mortality after traumatic brain injury. AB - BACKGROUND: Prediction of outcome after traumatic brain injury (TBI) remains elusive. We tested the use of a single hospital Glasgow Coma Scale (GCS) Score, GCS Motor Score, and the Head component of the Abbreviated Injury Scale (AIS) Score to predict 2-week cumulative mortality in a large cohort of TBI patients admitted to the eight U.S. Level I trauma centers in the TBI Clinical Trials Network. METHODS: Data on 2,808 TBI patients were entered into a centralized database. These TBI patients were categorized as severe (GCS score, 3-8), moderate (9-12), or complicated mild (13-15 with positive computed tomography findings). Intubation and chemical paralysis were recorded. The cumulative incidence of mortality in the first 2 weeks after head injury was calculated using Kaplan-Meier survival analysis. Cox proportional hazards regression was used to estimate the magnitude of the risk for 2-week mortality. RESULTS: Two week cumulative mortality was independently predicted by GCS, GCS Motor Score, and Head AIS. GCS Severity Category and GCS Motor Score were stronger predictors of 2-week mortality than Head AIS. There was also an independent effect of age (<60 vs. >=60) on mortality after controlling for both GCS and Head AIS Scores. CONCLUSIONS: Anatomic and physiologic scales are useful in the prediction of mortality after TBI. We did not demonstrate any added benefit to combining the total GCS or GCS Motor Scores with the Head AIS Score in the short-term prediction of death after TBI. PMID- 22071924 TI - Population-based study of the risk of in-hospital death after traumatic brain injury: the role of sepsis. AB - BACKGROUND: Traumatic brain injury (TBI) accounts for the largest proportion of injury-related deaths and disability in the United States. The proportion of TBI related deaths that occur after admission in a hospital remains high despite improvement in medical technology. We provide findings on the risk factors of in hospital death and demonstrate the risk associated with sepsis occurring in the hospital environment. METHODS: Population-based retrospective cohort study of 41,395 patients with TBI from all nonfederal hospitals in South Carolina, 1998 to 2009. TBI was ascertained by International Classification of Diseases-9th Rev. Clinical Modification codes of 800 to 801, 803 to 804, 850 to 854, and 959.01. Observation was censored at the 120th day. Days elapsing from the date of injury to date of death established the survival time (T). Cox regression was used to examine the risk of death, whereas Kaplan-Meier survival curves compared survival probabilities across time. RESULTS: Sepsis was independently associated with risk of in-hospital death with hazard ratio of 1.34 (p < 0.001). Severity of TBI was the strongest risk factor with hazard ratio of 4.97 (p < 0.001). Nearly 90% of patients with sepsis were identified with one of the nosocomial etiologies included in the analyses compared with 7% of patients without sepsis (p < 0.001). The survival probabilities were significantly lower for persons with sepsis compared with those without (log-rank test p < 0.001). CONCLUSION: Sepsis occurring in the hospital environment and associated with nosocomial etiologies is a strong risk factor for in-hospital death after TBI. Reducing the risk of infections and subsequent sepsis through adherence with infection control measures is a critical step to reduce in-hospital deaths among patients with TBI. PMID- 22071923 TI - Effect of the modified Glasgow Coma Scale score criteria for mild traumatic brain injury on mortality prediction: comparing classic and modified Glasgow Coma Scale score model scores of 13. AB - BACKGROUND: The Glasgow Coma Scale (GCS) classifies traumatic brain injuries (TBIs) as mild (14-15), moderate (9-13), or severe (3-8). The Advanced Trauma Life Support modified this classification so that a GCS score of 13 is categorized as mild TBI. We investigated the effect of this modification on mortality prediction, comparing patients with a GCS score of 13 classified as moderate TBI (classic model) to patients with GCS score of 13 classified as mild TBI (modified model). METHODS: We selected adult TBI patients from the Pennsylvania Outcome Study database. Logistic regressions adjusting for age, sex, cause, severity, trauma center level, comorbidities, and isolated TBI were performed. A second evaluation included the time trend of mortality. A third evaluation also included hypothermia, hypotension, mechanical ventilation, screening for drugs, and severity of TBI. Discrimination of the models was evaluated using the area under receiver operating characteristic curve (AUC). Calibration was evaluated using the Hosmer-Lemershow goodness of fit test. RESULTS: In the first evaluation, the AUCs were 0.922 (95% CI, 0.917-0.926) and 0.908 (95% CI, 0.903-0.912) for classic and modified models, respectively. Both models showed poor calibration (p < 0.001). In the third evaluation, the AUCs were 0.946 (95% CI, 0.943-0.949) and 0.938 (95% CI, 0.934-0.940) for the classic and modified models, respectively, with improvements in calibration (p = 0.30 and p = 0.02 for the classic and modified models, respectively). CONCLUSION: The lack of overlap between receiver operating characteristic curves of both models reveals a statistically significant difference in their ability to predict mortality. The classic model demonstrated better goodness of fit than the modified model. A GCS score of 13 classified as moderate TBI in a multivariate logistic regression model performed better than a GCS score of 13 classified as mild. PMID- 22071925 TI - Risk of venous thromboembolism after spinal cord injury: not all levels are the same. AB - BACKGROUND: Venous thromboembolism (VTE), a diagnosis that includes both deep vein thrombosis and pulmonary embolism, is a well-recognized complication following injury. Previous studies have identified multiple risk factors including spinal cord injury (SCI). We hypothesized that the level of SCI also influences the likelihood of VTE. METHODS: The National Trauma Data Bank was queried to identify all patients with SCI admitted in 2007 and 2008. Rates of VTE, demographics, admitting comorbidities, in-hospital complications, level of SCI (divided by National Trauma Data Bank into five groups), associated injuries, and outcome variables were abstracted. Multiple regression was used to identify independent risk factors for VTE. RESULTS: During the 2-year period, 18,302 patients were admitted with SCI. The overall rate of VTE was 4.3% but varied significantly depending on the level of SCI injury (chi(2), 44.8; p < 0.05). Patients with high cervical spine (C1-4) injury had a rate VTE of 3.4%, whereas patients with high thoracic spine (T1-6) injury had the highest rate of VTE at 6.3%. The lowest rate of VTE was in patients with lumbar injury (3.2%). There were no significant differences in the preexisting comorbidities or in-hospital complications among the five SCI groups with the exception of pneumonia. In a multiple logistic regression model, the level of SCI was an independent risk factor for VTE as was increasing age, increasing Injury Severity Score, male gender, traumatic brain injury, and chest trauma. CONCLUSIONS: The rate of VTE differs with various SCI levels. Patients with high thoracic (T1-6) injury seem to be at the highest risk and patients with high cervical (C1-4) injury at one of the lowest. A higher index of suspicion for VTE should therefore be maintained in patients with a high thoracic SCI. Further studies are required to elucidate the underlying mechanisms. PMID- 22071926 TI - Identification of motor and sensory fascicles in peripheral nerve trunk using immunohistochemistry and micro-Raman spectroscopy. AB - OBJECTIVE: To explore a time-efficient method of identifying motor and sensory fascicles in peripheral nerve trunk. METHODS: Thirty Wistar rats were selected to obtain whole spine. The spinal dorsal roots and ventral roots, and sciatic nerve were harvested as sensor, motor, and mixed samples, annexin V and agrin specificities were observed with Western blot and immunohistochemistry. A total of 32 New Zealand rabbits were selected and killed. The roots of spinal nerves were exposed under an operating microscope, and the ventral and dorsal roots, ~3 mm to 5 mm, were dissociated, and frozen as transverse sections of 30-MUm thickness. The sections were examined by micro-Raman spectroscopy. RESULTS: The annexin V and agrin were special substances of sensory and motor nerves, respectively, and can act as specific antigens for identifying different nerve fascicles. Sections of the same type of nerve fascicles showed reproducibility with similar spectral features. Significant differences in the spectral properties, such as the intensity and breadth of the peak, were found between motor and sensory fascicles in the frequency regions of 1,088 cm(-1), 1,276 cm( 1), 1,439 cm(-1), 1,579 cm(-1), and 1,659 cm(-1). With the peak intensity ratio of 1.06 (I(1276)/I(1439)) as a standard, we could identify motor fascicles with a sensitivity of 88%, specificity of 94%, positive predictive value of 93%, and negative predictive value of 88%. In the range of 2,700 cm(-1) to 3,500 cm(-1), the half-peak width of the motor fascicles was narrow and sharp, whereas that of the sensory fascicles was relatively wider. A total of 91% of the peak features were in accordance with the identification standard. CONCLUSION: Motor and sensory fascicles exhibit different characteristics in Raman spectra, which are constant and reliable. Therefore, it is more effective than immunohistochemistry method in identifying different nerve fascicles according to the specific spectrum, and it possesses feasibility for clinical application. PMID- 22071927 TI - Alcohol use by pedestrians who are struck by motor vehicles: how drinking influences behaviors, medical management, and outcomes. AB - BACKGROUND: Injuries to pedestrians struck by motor vehicles represent a significant public health hazard in large cities. The purpose of this study is to investigate the demographics of alcohol users who are struck by motor vehicles and to assess the effects of alcohol on pedestrian crossing patterns, medical management, and outcomes. METHODS: Data were prospectively collected between December 2008 to September 2010 on all pedestrians who presented to a Level I trauma center after being struck by a motor vehicle. Variables were obtained by interviewing patients, scene witnesses, first responders, and medical records. RESULTS: Pedestrians who used alcohol were less likely to cross the street in the crosswalk with the signal (22.6% vs. 64.7%) and more likely to cross either in the crosswalk against the signal (22.6% vs. 12.4%) or midblock (54.8% vs. 22.8%). Alcohol use was associated with more initial computed tomography imaging studies compared with no alcohol involvement. Alcohol use was associated with a higher Injury Severity Score (8.82 vs. 4.85; p < 0.001) and hospital length of stay (3.89 days vs. 1.82 days; p < 0.001) compared with those with no alcohol involvement. Patients who used alcohol had a lower average Glasgow Coma Scale score (13.80 vs. 14.76; p < 0.001) and a higher rate of head and neck, face, chest, abdomen, and extremity/pelvic girdle injuries (based on Abbreviated Injury Scale) than those with no alcohol involvement. CONCLUSION: Alcohol use is a significant risk factor for pedestrians who are struck by motor vehicles. These patients are more likely to cross the street in an unsafe manner and sustain more serious injuries. Traffic safety and injury prevention programs must address irresponsible alcohol use by pedestrians. PMID- 22071928 TI - Therapeutic hypothermia cardioprotection in murine hemorrhagic shock/resuscitation differentially affects p38alpha/p38gamma, Akt, and HspB1. AB - BACKGROUND: Therapeutic hypothermia (TH) has demonstrated great potential for forestalling cardiovascular collapse and improving outcomes in the setting of severe hemorrhagic shock (HS). We used an established mouse model of severe HS to study the response of interrelated cardiac-signaling proteins p38, HspB1, and Akt to shock, resuscitation, and cardioprotective TH. METHODS: Adult female C57BL6/J mice were bled and maintained at a mean arterial pressure of 35 mm Hg. After 30 minutes, mice were randomized to 120 minutes of TH (33 degrees C +/- 0.5 degrees C) or continued normothermia at 37 degrees C. After 90 minutes, animals were resuscitated and monitored for 180 minutes. Cardiac p38, Akt, and HspB1 phosphorylation (p-p38, p-Akt, and p-HspB1), expression, and Akt/HspB1 interactions were measured at serial time points during HS and resuscitation. Markers of mitochondrial damage (plasma cytochrome c), inflammation (myeloperoxidase), and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) were analyzed. RESULTS: By 15 minutes HS, p-p38 and p-HspB1 significantly increased while p-Akt(T308) decreased (p < 0.05). TH attenuated phosphorylation of the p38alpha isoform during HS and increased phosphorylation of the p38gamma isoform during both HS and early resuscitation (p < 0.05). TH increased Akt/HspB1 coimmunoprecipitation during early resuscitation and increased p-Akt and HspB1 expression during late resuscitation (p < 0.05). Finally, TH attenuated the myocardial myeloperoxidase and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and plasma cytochrome c during late resuscitation. CONCLUSIONS: TH increases phosphorylation of p38gamma during both HS and early resuscitation, but attenuates phosphorylation of p38alpha, increases Akt/HspB1 interaction, and modulates Akt phosphorylation during HS and resuscitation. Such TH-related signaling events are associated with reduced cardiac inflammation, apoptosis, and mitochondrial injury. PMID- 22071929 TI - Direct vascular control results in less physiologic derangement than proximal aortic clamping in a porcine model of noncompressible extrathoracic torso hemorrhage. AB - BACKGROUND: The optimal method of vascular control and resuscitation in patients with life-threatening, extrathoracic torso hemorrhage remains debated. Guidelines recommend emergency department thoracotomy (EDT) with aortic clamping, although transabdominal aortic clamping followed by vascular control and direct vascular control (DVC) without aortic clamping are alternatives. The objective of this study is to compare the effectiveness of three approaches to extrathoracic torso hemorrhage in a large animal model. METHODS: Adolescent swine (Sus Scrofa) (mean weight = 80.9 kg) were randomized into three groups all of which had class IV shock established by hemorrhage from an iliac artery injury. Group 1: EDT with thoracic aortic clamping (N = 6); group 2: transabdominal supraceliac aortic clamping (SCC; N = 6); and group 3: DVC of bleeding site without aortic clamping (N = 6). After hemorrhage, EDT or SCC was performed in groups 1 and 2, respectively, with subsequent exploration of the bleeding site and placement of a temporary vascular shunt (TVS). Group 3 (DVC) underwent direct exploration of the injury and placement of a TVS. All groups were resuscitated to predefined physiologic endpoints over 6 hours with repeated measures of central and cerebral perfusion and end-organ function at standardized time points. Postmortem tissue analysis was performed to quantify injury to critical tissue beds. RESULTS: There was no difference in mortality among the groups and no TVS failures. Central aortic pressure, carotid flow, and partial pressure brain tissue oximetry, all demonstrated increases in EDT and SCC after application of the aortic clamp relative to DVC (p < 0.05). During resuscitation, serum lactate levels were higher in EDT compared with SCC and DVC (6.85 vs. 3.08 and 2.15, respectively; p < 0.05) and serum pH in EDT reflected greater acidosis than SCC and DVC (7.24 vs. 7.36 and 7.39, respectively; p < 0.05). EDT and SCC required more intravenous fluid than DVC (2,166 mL and 2,166 mL vs. 667 mL, respectively; p < 0.05) and more vasopressors were used in EDT and SCC compared with DVC (52.1 MUg and 43.5 MUg vs. 12.4 MUg, respectively; p < 0.05). Brain and myocardial tissue stains demonstrated the same degree of acute ischemic changes in all groups. CONCLUSION: Although aortic clamping increases central and cerebral perfusion, DVC results in less physiologic derangement. The optimal method of aortic control would incorporate the benefits of maintained central pressure with less associated morbidity. Clinical studies evaluating DVC are warranted. PMID- 22071930 TI - Burn injury dampens erythroid cell production through reprioritizing bone marrow hematopoietic response. AB - BACKGROUND: Anemia in burn patients is due to surgical blood loss and anemia of critical illness. Because the commitment paradigm of common bone marrow progenitors dictates the production of erythroid, myeloid, and lymphoid cells, we hypothesized that skewed bone marrow lineage commitment decreases red cell production and causes anemia after a burn injury. METHODS: After anesthesia, B(6)D(2)F(1) mice received a 15% total body surface area dorsal scald burn. The sham group did not receive scald burn. Femoral bone marrow was harvested on 2, 5, 7, 14, and 21 postburn days (PBD). Total bone marrow cells were labeled with specific antibodies to erythroid (CD71/Ter119), myeloid (CD11b), and lymphoid (CD19) lineages and analyzed by flow cytometry. To test whether erythropoietin (EPO) could increase red blood cell production, EPO was administered to sham and burn animals and their reticulocyte response was measured on PBD 2 and PBD 7. RESULTS: Burn injury reduced the erythroid cells of the bone marrow from 35% in sham to 17% by PBD 5 and remained at similar level until PBD 21. Myeloid cells, however, increased from 42% in sham to 60% on PBD 5 and 77% on PBD 21. Burn injury reduced reticulocyte counts on PBD 2 and PBD 7 indicating that the erythroid compartment is severely depleted. This depleted compartment, however, responded to EPO but was not sufficient to change red cell production. CONCLUSION: Burn injury skews the bone marrow hematopoietic commitment away from erythroid and toward myeloid cells. Shrinkage of the erythroid compartment contributes to resistance to EPO and the anemia of critical illness. PMID- 22071931 TI - Open versus closed abdomen treatment on liver function in rats with sepsis and abdominal compartment syndrome. AB - BACKGROUND: Despite recent advances in understanding the mechanisms of sepsis and abdominal compartment syndrome (ACS) and of improvements in their management, the mortality rates from these conditions remain high. Few studies have compared liver injuries in patients undergoing open and closed abdomen treatment. The aim of this study was to compare the effects of open versus conservative abdominal closure approaches upon liver function using a controlled and randomized model of intra-abdominal hypertension and sepsis in a rat model. METHODS: Healthy Sprague Dawley rats underwent cecal ligation and puncture to induce sepsis, followed by intraperitoneal injection of air to induce intra-abdominal hypertension. Twenty four hours later, the rats were randomly divided into two groups, one (n = 36) undergoing abdominal closure and the other (n = 36) undergoing open abdomen. Rats were killed after 1 hour, 6 hours, 1 day, 3 days, 5 days, and 7 days. Liver injury was evaluated by Hepatic Injury Severity Scoring. The levels of expression of Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha, interleukin-6, signaling transducer and activator of transcription 3 mRNA, and suppressor of cytokine signaling 3 mRNA were assayed by reverse transcription-polymerase chain reaction. RESULTS: The levels of tumor necrosis factor-alpha, interleukin-6, and signaling transducer and activator of transcription 3 mRNA were higher, and those of TLR4 and suppressor of cytokine signaling 3 mRNA were lower, in the open than in the closed group (p < 0.05 each). Serum concentrations of aspartate aminotransferase and alanine aminotransferase were also lower in the open group (p < 0.05 each). CONCLUSIONS: Open abdominal management may improve liver regeneration soon after surgery, as well as reducing inflammatory responses, by reducing TLR4 expression. PMID- 22071932 TI - Limited transthoracic echocardiogram: so easy any trauma attending can do it. AB - BACKGROUND: Limited transthoracic echocardiogram (LTTE) represents an attractive alternative to formal transthoracic echocardiogram (TTE), because it does not require an echocardiogram machine. Our hypothesis is that trauma attendings can learn LTTE effectively with minimal training. METHODS: Seven attendings at a Level I trauma center received didactic and hands-on training in LTTE and performed this test on hypotensive patients to evaluate for contractility, fluid status, and pericardial effusion. Therapy to improve perfusion (administration of fluids, ionotropes, or vasopressors) was guided by LTTE findings. Perfusion status was determined by serum lactate level before and 6 hours after LTTE. Findings were compared with cardiology-performed TTE. RESULTS: Range of postresidency training was 1 year to 29 years. LTTE teaching entailed 70 minutes of didactics and 25 minutes of hands-on. In all, 52 LTTEs were performed; two patients were excluded due to blunt trauma arrest. Age ranged from 22 years to 89 years with an average of 55 years. Admission diagnosis was blunt trauma (n = 34), penetrating trauma (n = 3), and intra-abdominal sepsis (n = 13). Average time for LTTE was 4 minutes 38 seconds. Cardiology-performed TTE was obtained in all patients, and correlation with LTTE was 100%. A total of 37 patients received intravenous fluid, 9 received vasopressors, and 4 received ionotropes as guided by LTTE findings, with lactate reduction in all patients (p < 0.00001). Attendings scored a mean of 88% in a written test after training. CONCLUSIONS: Trauma attendings can successfully learn LTTE with minimal training and use the technique as a resuscitation tool in the hypotensive patient. PMID- 22071933 TI - Low-intensity pulsed ultrasound as a useful adjuvant during distraction osteogenesis: a prospective, randomized controlled trial. AB - BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) was proven to have a positive impact on bone healing in animal and clinical studies. METHODS: In this prospective, randomized controlled trial the effect of LIPUS during distraction osteogenesis was investigated. Thirty-six patients who underwent distraction osteogenesis (>2 cm) were enrolled. Sixteen patients in the treatment group received LIPUS, and 20 patients as control group did not. Ultrasound treatment device was transcutaneously applied at the distraction gap for 20 minutes daily (frequency 1.5 MHz, signal burst with 200 MUs, signal repetition frequency 1.0 kHz, intensity 30 mW/cm(2)). Evaluation of patients was performed by standard radiographs every 3 weeks to 4 weeks. RESULTS: Average transport distance was 7.0 cm in the ultrasound group and 6.3 cm in the control group. Mean Paley index for the ultrasound group was 1.09 mo/cm and 1.49 mo/cm for the control group. Mean distraction consolidation index for the ultrasound group was 32.8 d/cm and 44.6 d/cm for the control group. The calculated indices indicated no significant statistical difference between the two groups (p < 0.116) but the fixator gestation period could be decreased for 43.6 days in the treatment group. CONCLUSIONS: Therapeutic application of LIPUS during callus distraction constitutes a useful adjuvant treatment during distraction osteogenesis and has a positive effect on healing time with no negative effects. PMID- 22071934 TI - Are certain fractures at increased risk for compartment syndrome after civilian ballistic injury? AB - BACKGROUND: Compartment syndrome after ballistic fracture is uncommon but potentially devastating. Few data are available to help guide clinicians regarding risk factors for developing compartment syndrome after ballistic fractures. Our primary hypothesis was that ballistic fractures of certain bones would be at higher risk for development of compartment syndrome. METHODS: A retrospective review at a Level I trauma center from 2001 through 2007 yielded 650 patients with 938 fractures resulting from gunshots. We reviewed all operative notes, clinic notes, discharge summaries, and data from our prospective trauma database. Cases in which the attending orthopedic surgeon diagnosed compartment syndrome and performed fasciotomy were considered cases with compartment syndrome. We excluded all prophylactic fasciotomies. Univariate analyses were conducted to identify risk factors associated with development of compartment syndrome. RESULTS: Twenty-six (2.8%) of the 938 fractures were associated with compartment syndrome. Only fibular (11.6%) and tibial (11.4%) fractures had incidence significantly higher than baseline for all ballistic fractures (p < 0.001). Fractures of the proximal third of the fibula were more likely to result in compartment syndrome than fractures of the middle or distal third (p = 0.03), as were fractures of the proximal third of the tibia (p = 0.01). No other demographic or injury parameters were associated with compartment syndrome. CONCLUSION: Ballistic fractures of the fibula and tibia are at increased risk for development of compartment syndrome over other ballistic fractures. We recommend increased vigilance when treating these injuries, particularly if the fracture is in the proximal aspect of the bone or is associated with vascular injury. PMID- 22071935 TI - Nontrauma emergency surgery: optimal case mix for general surgery and acute care surgery training. AB - BACKGROUND: To examine the case mix and patient characteristics and outcomes of the nontrauma emergency (NTE) service in an academic Division of Acute Care Surgery. METHODS: An NTE service (attending, chief resident, postgraduate year-3 and postgraduate year-2 residents, and two physician assistants) was created in July 2005 for all urgent and emergent inpatient and emergency department general surgery patient consults and admissions. An NTE database was created with prospective data collection of all NTE admissions initiated from November 1, 2007. Prospective data were collected by a dedicated trauma registrar and Acute Physiology and Chronic Health Evaluation-intensive care unit (ICU) coordinator daily. NTE case mix and ICU characteristics were reviewed for the 2-year time period January 1, 2008, through December 31, 2009. During the same time period, trauma operative cases and procedures were examined and compared with the NTE case mix. RESULTS: Thousand seven hundred eight patients were admitted to the NTE service during this time period (789 in 2008 and 910 in 2009). Surgical intervention was required in 70% of patients admitted to the NTE service. Exploratory laparotomy or laparoscopy was performed in 449 NTE patients, comprising 37% of all surgical procedures. In comparison, only 118 trauma patients (5.9% of admissions) required a major laparotomy or thoracotomy during the same time period. Acuity of illness of NTE patients was high, with a significant portion (13%) of NTE patients requiring ICU admission. NTE patients had higher admission Acute Physiology and Chronic Health Evaluation III scores [61.2 vs. 58.8 (2008); 58.2 vs. 55.8 (2009)], increased mortality [(9.71% vs. 4.89% (2008); 6.78% vs. 5.16% (2009)], and increased readmission rates (15.5% vs. 7.4%) compared with the total surgical ICU (SICU) admissions. CONCLUSION: In an era of declining operative caseload in trauma, the NTE service provides ample opportunity for complex general surgery decision making and operative procedures for surgical residency education, including advanced surgical critical care management. In addition, creation of an NTE service provides an optimal general surgery case mix, including major abdominal operations, that can augment declining trauma surgery caseloads, maintain acute care faculty surgical skills, and support general and acute care surgery residency training. PMID- 22071936 TI - American College of Surgeons' Committee on Trauma Performance Improvement and Patient Safety program: maximal impact in a mature trauma center. AB - BACKGROUND: To examine the impact of an ongoing comprehensive performance improvement and patient safety (PIPS) program implemented in 2005 on mortality outcomes for trauma patients at an established American College of Surgeons (ACS) verified Level I Trauma Center. METHODS: The primary outcome measure was in hospital mortality. Age, Injury Severity Score (ISS), and intensive care unit admissions were used as stratifying variables to examine outcomes over a 5-year period (2004-2008). Institution mortality rates were compared with the National Trauma Data Bank mortality rates stratified by ISS score. Enhancements to our comprehensive PIPS program included revision of trauma activation criteria, development of standardized protocols for initial resuscitation, massive transfusion, avoidance of over-resuscitation, tourniquet use, pelvic fracture management, emphasis on timely angiographic and surgical intervention, prompt spine clearance, reduction in time to computed tomography imaging, reduced dwell time in emergency department, evidence-based traumatic brain injury management, and multidisciplinary efforts to reduce healthcare-associated infections. RESULTS: In 2004 (baseline data), the in-hospital mortality rate for the most severely injured trauma patients (ISS >24) at our trauma center was 30%, consistent with the reported mortality rate from the National Trauma Data Bank for patients with this severity of injury. Over 5 years, our mortality rate decreased significantly for severely injured patients with an ISS >24, from 30.1% (2004) to 18.3% (2008), representing a 12% absolute reduction in mortality (p = 0.011). During the same 5-year time period, the proportion of elderly patients (age >65 years) cared for at our trauma center increased from 23.5% in 2004 to 30.6% in 2008 (p = 0.0002). Class I trauma activations increased significantly from 5.5% in 2004 to 15.5% in 2008 based on our reclassification. A greater percentage of patients were admitted to the intensive care unit (25.8% in 2004 to 37.3% in 2007 and 30.4% in 2008). No difference was identified in the rate of blunt (95%) or penetrating (5%) mechanism of injury in our patients over this time period. Trauma Quality Improvement Program confirmed improved trauma outcomes with observed-to-expected ratio and 95% confidence intervals of 0.64 (0.42-0.86) for all patients, 0.54 (0.15-0.91) for blunt single-system patients, and 0.78 (0.51-1.06) for blunt multisystem patients. CONCLUSION: Implementation of a multifaceted trauma PIPS program aimed at improving trauma care significantly reduced in-hospital mortality in a mature ACS Level I trauma center. Optimal care of the injured patient requires uncompromising commitment to PIPS. PMID- 22071937 TI - Initial treatment of ocular exposure and associated complications in severe periorbital thermal injuries. PMID- 22071938 TI - Efficacy and safety of intensive insulin therapy for critically ill neurologic patients: a meta-analysis. AB - BACKGROUND: Whether intensive insulin therapy (IIT) may improve clinical outcomes for patients admitted to intensive care units, especially critically ill neurologic patients, is still debated. In the present study, we performed a meta analysis of literature comparing the efficacy and safety of IIT and conventional insulin therapy (CIT) for critically ill neurologic patients in terms of mortality, infection rate, neurologic outcome, and hypoglycemia. METHODS: We searched for published reports of studies of randomized control trials (up to March 10, 2011) of patients admitted to neurologic intensive care units and investigated an IIT (target of blood glucose control <120 mg/dL) with a control of CIT. Data were abstracted by a standardized protocol. RESULTS: We retrieved reports of five studies involving 924 patients. The risk of mortality, infection rate, and neurologic outcome did not differ with IIT or CIT. However, the incidence of hypoglycemic episodes was significantly higher with IIT than CIT (78.8% vs. 48.9%), with a relative risk of 2.62 (95% confidence interval [CI]: 1.07-6.43; p < 0.04). CONCLUSIONS: As compared with CIT, IIT may not benefit critically ill neurologic patients in terms of mortality, infection rate, or neurologic outcome and in fact may be associated with increased hypoglycemic complications. Therefore, IIT cannot be recommended over conventional control for critical neurologic disease, but further study is warranted. PMID- 22071939 TI - A systematic review of an emerging consciousness population: focus on program evolution. PMID- 22071940 TI - Indirect colonic injury after military wounding: a case series. AB - BACKGROUND: Colonic trauma in wartime most commonly results from direct injury along the path of a penetrating missile. Rarely, the colon may be injured by primary blast effect or by propagation of energy by the missile, remote from the track of the projectile. METHODS/RESULTS: This article describes the clinical presentation and operative findings in five patients who sustained high energy transfer gunshot wounds (GSWs) or fragmentation injuries from blast who were found to have sustained colonic injuries anatomically remote from the missile track/s. CONCLUSIONS: Military surgeons should be aware of the phenomenon of indirect injury to the colon after high-energy transfer GSW and blast injury. A high index of suspicion should be maintained and cross-sectional imaging used where feasible. Primary colonic reconstruction was used safely in these patients with indirect colonic injuries. PMID- 22071941 TI - Complete thoracic tracheal transection caused by blunt trauma. PMID- 22071942 TI - Left pulmonary artery transection after penetrating thoracic trauma. PMID- 22071943 TI - Sew it up! A Western Trauma Association multiinstitutional study of enteric injury management in the postinjury open abdomen. PMID- 22071944 TI - Platelet activation accounts for excessive angiopoietin-1 levels in patients' sera. PMID- 22071946 TI - Repair of blunt thoracic outlet arterial injuries: an evolution from open to endovascular approach. AB - BACKGROUND: Thoracic outlet artery injuries due to blunt trauma are uncommon. Exposure of these arteries is associated with significant morbidity and mortality. An endovascular approach is a less invasive alternative approach for these technically challenging injuries. METHODS: A retrospective review of patients who presented with blunt traumatic injuries to the innominate, subclavian, and axillary arteries between 1998 and 2009 was performed. Demographic data, concomitant injuries, preoperative workup, treatment, and outcomes were recorded. RESULTS: During the study period, 34 patients (80% men) meeting selection criteria were admitted (11 innominate, 16 subclavian, and 7 axillary). Management was nonoperative in 6, open in 16, and endovascular in 12 patients. In the latter group, eight patients had successful stent-graft insertions. These were approached in an antegrade femoral or retrograde brachial fashion. In three cases of complete artery transaction, both methods were used. Shorter operative time (149 minutes vs. 230 minutes; p = 0.03) and less blood loss (50 mL vs. 1,225 mL; p = 0.03) were seen in the endovascular group compared with the open repair group. There was a trend for less blood transfusion, but it was not significant (0 median units vs. 4.5 median units; p = 0.3). Hospital length of stay was shorter (19 days vs. 29 days; p = 0.4). CONCLUSIONS: Covered stents are a feasible alternative to open repair in the multiply injured blunt trauma patients with thoracic outlet arterial injuries. This can be used in the damage control setting as it offers shorter operative time, less blood loss, and overall less morbidity to the patient. Long-term follow-up is needed. PMID- 22071947 TI - Late iatrogenic coronary artery stenosis after penetrating cardiac trauma repair. PMID- 22071948 TI - Daily functioning and health status in patients with hand osteoarthritis: Fewer differences between women and men than expected. AB - OBJECTIVE: To explore and describe potential differences between women and men in functioning, health status and socio-economic variables in hand OA. METHODS: Unselected patients of an Austrian outpatient clinic meeting the ACR criteria for hand OA were consecutively included and assessed once. Descriptive statistics and subgroup analyses were performed for differences between women and men. By regression analysis, we explored whether the variables sex, practice of sports, manual activities, aesthetic changes and functioning in daily life predict the levels of pain and vitality. RESULTS: 223 (88.1%) women and 30 (11.9%) men were included in the study. Significant differences between women and men were found in involvement in housework, aesthetic changes and own net income. Sex did not contribute significantly to any of the regression models, while e.g. involvement in sports was a strong individual contributor to self-reported vitality - irrespective of sex. Total X-ray scores of both hands as well as the involvement of CMCI joints did not show significant differences. CONCLUSION: Our study showed significant differences between women and men with hand OA in socio-economic variables and aesthetic changes. In contrast to our expectations, no other differences between women and men were found in functioning and health status. PMID- 22071953 TI - Local temperature measurements on nanoscale materials using a movable nanothermocouple assembled in a transmission electron microscope. AB - A nanoscale thermocouple consisting of merged Cu and Cu-Ni tips is developed for local temperature measurements on advanced nanomaterials by using a probing technique in a high-resolution transmission electron microscope (TEM) equipped with a double probe scanning tunneling microcopy (STM) unit. The fabricated nanothermocouple works as the so-called T-type thermocouple and displays a quick response and high spatial and thermal resolutions. A generated thermoelectromotive force which reflects rapid temperature changes controlled by electron beam intensity alternations on a metal nanoelectrode proves the technique's usefulness for high-precision local temperature measurements. The developed method demonstrates the effectiveness while also measuring temperature changes in Joule heated multi-walled carbon nanotubes (CNTs) and in a modeled electrical conductive composite nanosystem. PMID- 22071954 TI - The clinical value of single photon emission computed tomography myocardial perfusion imaging in cardiac risk stratification of very elderly patients (>=80 years) with suspected coronary artery disease. AB - BACKGROUND: The role of single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) in cardiac evaluation of the very elderly patients is unclear. We investigated the clinical value of SPECT MPI in very elderly patients (>=80 years) with suspected coronary artery disease (CAD) as well as in comparison to younger patients. METHODS AND RESULTS: A retrospective analysis of prospectively collected data from 8,864 patients [1,093 patients >=80 years (very elderly), 3,369 patients 65-79 years (elderly), and 4,402 patients 50-64 years (middle-aged)] with suspected CAD who underwent exercise and/or pharmacologic stress testing with SPECT MPI between 1996 and 2005 was performed. Clinical and SPECT MPI characteristics, cardiac event rates, early (<=60 days) cardiac catheterization and revascularization rates of very elderly patients were compared to that of younger patients. Mean follow-up for cardiac events (cardiac death or non-fatal myocardial infarction) was 1.9 +/- 0.9 years. Very elderly patients with moderate to severely abnormal SSS had a significantly higher annualized cardiac event rate than those with mildly abnormal or normal study (9.6% vs 3.4% and 2.5% respectively, P < .001). Across all categories of SSS, very elderly patients had a significantly higher cardiac event rate as compared to younger patients (P < .001). Early cardiac catheterization and revascularization referrals in very elderly patients increased as a function of severity of ischemia on SPECT MPI (P < .001), although these referral rates were significantly lower in very elderly patients with mild to moderate and severe ischemia as compared to younger patients (P < .05). CONCLUSIONS: In very elderly patients (>=80 years) with suspected CAD, SPECT MPI has prognostic and incremental value in the noninvasive cardiovascular assessment for risk stratification and may influence medical decisions. PMID- 22071955 TI - Highlights of the 2011 Scientific Session of the American Society of Nuclear Cardiology: Denver, Colorado, September 8-11, 2011. PMID- 22071956 TI - Contemporary insights into painful diabetic neuropathy and treatment with spinal cord stimulation. AB - A substantial body of literature is available on the natural history of diabetes, but much less is understood of the natural history of painful diabetic peripheral neuropathy (PDPN), a pervasive and costly complication of diabetes mellitus. Multiple mechanisms have been proposed, including polyol pathway activation, advanced glycosylation end-product formation, and vasculopathic changes. Nevertheless, specific treatment modalities addressing these basic issues are still lacking. The mainstay of treatment includes pharmacological management with antidepressants, anticonvulsants, and opioids, but these drugs are often limited by unfavorable side-effect profiles. For over 30 years, spinal cord stimulation (SCS) has been used extensively for the management of various chronic neuropathic pain states. In the past decade, interest in the use of SCS for treatment of PDPN has increased. This article reviews pathophysiological mechanisms of PDPN, proposed mechanisms of SCS, and the role of SCS for the treatment of PDPN. PMID- 22071957 TI - Measurement of isoprene solubility in water, human blood and plasma by multiple headspace extraction gas chromatography coupled with solid phase microextraction. AB - The aim of this study was to determine the solubility (liquid-to-air ratios) of isoprene in water, human blood and plasma. To this end, an experimental setup combining multiple headspace extraction, solid phase microextraction and gas chromatography-mass spectrometry was applied. The water:air partition coefficients of isoprene were determined for the temperature range 4.5-37 degrees C and amounted to 1.171-0.277 (g mL(l)(-1)) (g mL(a)(-1))(-1). On the basis of these data, the enthalpy of volatilization was calculated as 29.46 +/- 2.83 kJ mol(-1). The blood:air partition coefficients at 37 degrees C were determined for ten normal healthy volunteers spread around a median value of 0.95 +/- 0.09 (g mL(l)(-1)) (g mL(a)(-1))(-1) and were approximately 16% lower than the plasma:air partition coefficients (1.11 +/- 0.2). The applied methodology can be particularly attractive for solubility studies targeting species at very low concentrations in the solution, i.e. when headspace sample enrichment is necessary to provide sufficient measurement sensitivity and reliability. This can be especially helpful if environmental or physiological solute levels have to be considered. PMID- 22071958 TI - Role of newly formed platelets in thrombus formation in rat after clopidogrel treatment: comparison to the reversible binding P2Y12 antagonist ticagrelor. AB - Platelet P2Y12 receptors play an important role in arterial thrombosis by stimulating thrombus growth. Both irreversibly (clopidogrel) and reversibly binding (ticagrelor, AZD6140) P2Y12 antagonists are clinically used for restricted periods, but possible differences in platelet function recovery after drug cessation have not been investigated. We treated WKY rats with a single, high dose of 200 mg/kg clopidogrel or 40 mg/kg ticagrelor. Blood was collected at different time points after treatment. Flow cytometry confirmed full platelet protection against ADP-induced alphaIIbbeta3 activation shortly after clopidogrel or ticagrelor treatment. At later time points after clopidogrel treatment, a subpopulation of juvenile platelets appeared that was fully responsive to ADP. Addition of ticagrelor to clopidogrel-treated blood reduced alphaIIbbeta3 activation of the unprotected platelets. In contrast, at later time points after ticagrelor treatment, all platelets gradually lost their protection against ADP activation. Perfusion experiments showed abolishment of thrombus formation shortly after clopidogrel or ticagrelor treatment. Thrombus formation on collagen was determined under high shear flow conditions. At later time points, large thrombi formed in the clopidogrel but not in the ticagrelor group, and unprotected, juvenile platelets preferentially incorporated into the formed thrombi. However, platelets from both groups were still similarly reduced in assays of whole blood aggregation. Conclusively, recovery of rat platelet function after ticagrelor differs mechanistically from that after clopidogrel. This difference is masked by conventional platelet aggregation methods, but is revealed by thrombus formation measurement under flow. Juvenile platelets formed at later time points after clopidogrel treatment promoted thrombus formation. PMID- 22071959 TI - Discoidin domain receptor 2 deficiency predisposes hepatic tissue to colon carcinoma metastasis. AB - BACKGROUND: The transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts is a major mechanism for stroma development in hepatic metastasis, but their regulatory pathways remain unclear. Transdifferentiated HSCs from fibrotic liver express high levels of the fibrillar collagen receptor discoidin domain receptor 2 (DDR2), but it is unclear if DDR2 plays a direct profibrogenic role in the tumour microenvironment. AIM: To assess the impact of DDR2 on the prometastatic role of HSC-derived myofibroblasts. METHODS: Hepatic metastases were induced in DDR2(-/-) and DDR2(+/+) mice by intrasplenic injection of MCA38 colon carcinoma cells, and their growth and features were characterised. Stromagenic, angiogenic and cancer cell proliferation responses were quantified in metastases by immunohistochemistry. The adhesion-, migration- and proliferation-stimulating activities of supernatants from primary cultured DDR2( /-) and DDR2(+/+) HSCs, incubated in MCA38 cell-conditioned medium, were evaluated in primary cultured liver sinusoidal endothelium cells (LSECs) and MCA38 cells. Gene expression signatures from freshly isolated DDR2(-/-) and DDR2(+/+) HSCs were compared and DDR2-regulated genes were studied by RT-PCR under basal conditions and after stimulation with MCA38 tumour-conditioned media. RESULTS: Metastases were increased three fold in DDR2(-/-) livers, and contained a higher density of alpha-smooth muscle actin-expressing myofibroblasts, CD31 expressing microvessels and Ki67-expressing MCA38 cells than metastases in DDR2(+/+) livers. Media conditioned by MCA38-activated DDR2(-/-) HSCs significantly increased adhesion, migration and proliferation of LSECs and MCA38 cells, compared with DDR2(+/+) HSCs. DDR2 deficiency in HSCs led to decreased gene expression of interferon gamma-inducing factor interleukin (IL)-18 and insulin-like growth factor-I; and increased gene expression of prometastatic factors IL-10, transforming growth factor (TGF)beta and vascular endothelial growth factor (VEGF), bone morphogenetic protein-7 and syndecan-1. MC38 tumour conditioned media further exacerbated expression changes in DDR2-dependent IL-10, TGFbeta and VEGF genes. CONCLUSION: DDR2 deficiency fosters the myofibroblast transdifferentiation of tumour-activated HSCs, generating a prometastatic microenvironment in the liver via HSC-derived factors. These findings underscore the role of stromal cells in conditioning the hepatic microenvironment for metastases through altered receptor-stroma interactions. PMID- 22071961 TI - Multiple giant prostatic urethral stones with an ureteral stone in a young patient. AB - Giant prostatic urethral stones have been reported as a very rare entity, and the etiology of these stones is not clear. We report a case of a 40-year-old man with giant multiple prostatic urethral stones whereby the entire gland was replaced, and a big ureteral stone presented with voiding difficulty and recurrent urinary tract infections. In the literature, to our knowledge, this is the youngest case wherein giant prostatic urethral stones coexisted with a big ureteral stone. Many different-sized stones were observed endoscopically, some protruding into the urethra, and some filling different cavities on the prostate. Following cystoscopy, multiple giant prostatic stones weighing a total of 151 g were removed by the open retropubic route. We treated the big ureteral stone endoscopically. PMID- 22071962 TI - Wolff-Parkinson-White Syndrome and myocardial infarction in ventricular fibrillation arrest: a case of two one-eyed tigers. PMID- 22071963 TI - Pseudomembranous necrotizing tracheobronchial aspergillosis. PMID- 22071960 TI - Trigeminal artery: a review of normal and pathological features. AB - OBJECTS: Carotid-vertebrobasilar anastomoses-the trigeminal, otic, hypoglossal, and proatlantal intersegmental arteries-serve as transitory channels between primitive internal carotid arteries and bilateral longitudinal neural arterial plexus, which is the precursor of future basilar artery, when the human embryo reaches about 4-mm length. MATERIAL AND METHODS: Normal and/or abnormal morphofunctional aspects of the prenatal and postnatal forms of the trigeminal artery are described according to personal and literature data. Many arteries of similar origin and course are also noted in the differential diagnosis of the trigeminal artery. CONCLUSIONS: The persistent primitive trigeminal artery, as the most commonly carotid-vertebrobasilar anastomosis, has a reported incidence of 0.03-2.2% in the literature. There is female sex predilection, and it may be discovered in patients of any age, on either side, and in association with many vascular variants. Although the significance of persistent primitive trigeminal artery regarding the development of an aneurysm or association with another pathological condition may not be clear, its (ab)normal morphology is the inspiration for anatomists, especially for neurosurgeons, before planning diagnostic and therapeutic procedures. PMID- 22071964 TI - Back to basics: ankle reflex in the evaluation of peripheral neuropathy in type 2 diabetes mellitus. AB - BACKGROUND: Ankle reflex is a simple screening tool frequently used in the detection of peripheral neuropathy. AIM: The purpose of this study is to assess the performance characteristics of ankle reflex in detecting diabetic peripheral neuropathy (DPN) by evaluating the sensitivity, specificity and the predictive ability of the ankle reflex, a component of Neuropathy Disability Score (NDS) with reference to Nerve Conduction Studies (NCS). METHODS: A total of 151 patients with type 2 diabetes were assessed (47 males, 104 females). Grading of neuropathy was done using Neuropathy Symptom Score (NSS), NDS and NCS. Patients were divided into two groups, those with abnormal NCS (Group 1) and those with normal NCS (Group 2). Demographic characteristics, biochemistry, NSS and NDS were assessed between the two groups. Taking NCS as the gold standard, sensitivity, specificity and predictive ability of the ankle reflex were calculated and compared with other tests included in NDS, namely vibration sense, superficial pain and temperature sensation. RESULTS: There were 59 (39.1%) patients in Group 1 and 92 (60.9%) in Group 2. NSS and NDS demonstrated strong positive association with NCS. Taking NCS as the gold standard, ankle reflex yielded the highest sensitivity and specificity (91.5 and 67.4%, respectively), closely followed by that of vibration sense. CONCLUSION: Ankle reflex is a powerful screening tool with high sensitivity and negative predictive value, but a combination of ankle reflex and vibration sense has superior sensitivity and specificity compared with either of them done alone for the detection of DPN in clinical settings. PMID- 22071965 TI - The prognostic variables predictive of mortality in patients with an exacerbation of COPD admitted to the ICU: an integrative review. AB - INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) frequently presents with an acute exacerbation (AECOPD). Debate exists as to whether these patients should be admitted to intensive care units (ICUs). An integrative review was performed to determine whether clinical variables available at the time of ICU admission are predictive of the intermediate-term mortality of patients with an AECOPD. METHODS: An integrative review was structured to incorporate a five-stage review framework to facilitate data extraction, analysis and presentation. The quality of the studies contributing to the integrative review was assessed with a novel scoring system developed from previously published data and adapted to this setting. RESULTS: The integrative review search strategy identified 28 studies assessing prognostic variables in this setting. Prognostic variables associated with intermediate-term mortality were low Glasgow Coma Scale (GCS) on admission to ICU, cardio-respiratory arrest prior to ICU admission, cardiac dysrhythmia prior to ICU admission, length of hospital stay prior to ICU admission and higher values of acute physiology scoring systems. Premorbid variables such as age, functional capacity, pulmonary function tests, prior hospital or ICU admissions, body mass index and long-term oxygen therapy were not found to be associated with intermediate-term mortality nor was the diagnosis attributed to the cause of the AECOPD. DISCUSSION: Variables associated with intermediate-term mortality after AECOPD requiring ICU admission are those variables, which reflect underlying severity of acute illness. Premorbid and diagnostic data have not been shown to be predictive of outcome. A scoring system is proposed to assess studies of prognosis in AECOPD. PMID- 22071966 TI - Interferon-beta efficiently inhibited endothelial progenitor cell-induced tumor angiogenesis. AB - Neovascularization has a critical role in the growth and metastatic spread of tumors, and involves recruitment of circulating endothelial progenitor cells (EPCs) from bone marrow. In this study, we examined whether EPCs could promote tumor angiogenesis, and found that the tumor growth was enhanced by the administration of EPCs. To test the hypothesis that genetically modified bone marrow-derived EPCs can be effective carriers of therapeutic agents to tumor sites, we conducted human interferon-beta (HuIFN-beta) gene transfection of EPCs with a virus vector in vitro. When HuIFN-beta was applied in the ex vivo culture of EPCs, HuIFN-beta-transduced EPCs achieved efficient killing of the total population of SPC-A1 cells, indicating a bystander effect was elicited by HuIFN beta-transduced EPCs in vitro. When SCP-A1 cancer cells were coimplanted along with ex vivo cultivated EPCs subcutaneous injection in nude mice, the tumor growth was increased. However, the anti-tumor effect of interferon-beta (IFN beta) offset the tumor-progressive character of EPCs and the tumor growth, and the vascular density of tumor tissues increased by coimplanted EPCs were decreased upon IFN-beta treatment. In addition, overall expression levels of vascular endothelial growth factor in tumor tissues were decreased upon IFN-beta treatment. Therefore, our results suggest that gene-transfected EPCs could be useful as a tumor-specific drug delivery system. PMID- 22071967 TI - Cross-presentation of tumour antigens by human induced pluripotent stem cell derived CD141(+)XCR1+ dendritic cells. AB - Monocyte-derived dendritic cells (moDC) have been widely used in cancer immunotherapy but show significant donor-to-donor variability and low capacity for the cross-presentation of tumour-associated antigens (TAA) to CD8(+) T cells, greatly limiting the success of this approach. Given recent developments in induced pluripotency and the relative ease with which induced pluripotent stem (iPS) cell lines may be generated from individuals, we have succeeded in differentiating dendritic cells (DC) from human leukocyte antigen (HLA) A(*)0201(+) iPS cells (iPS cell-derived DC (ipDC)), using protocols compliant with their subsequent clinical application. Unlike moDC, a subset of ipDC was found to coexpress CD141 and XCR1 that have been shown previously to define the human equivalent of mouse CD8alpha(+) DC, in which the capacity for cross presentation has been shown to reside. Accordingly, ipDC were able to cross present the TAA, Melan A, to a CD8(+) T-cell clone and stimulate primary Melan A specific responses among naive T cells from an HLA-A(*)0201(+) donor. Given that CD141(+)XCR1(+) DC are present in peripheral blood in trace numbers that preclude their clinical application, the ability to generate a potentially unlimited source from iPS cells offers the possibility of harnessing their capacity for cross-priming of cytotoxic T lymphocytes for the induction of tumour-specific immune responses. PMID- 22071968 TI - Non-myeloablative transplantation of bone marrow expressing self-antigen establishes peripheral tolerance and completely prevents autoimmunity in mice. AB - Myeloablative transplantation of bone marrow (BM) engineered to express myelin oligodendrocyte glycoprotein (MOG) establishes central intrathymic tolerance and completely prevents MOG-induced experimental autoimmune encephalomyelitis (EAE) in mice. Here we asked whether non-myeloablative transplantation of MOG expressing BM (pMOG-bone marrow transplantation (BMT)) can also provide the same protection. Using stepwise reduction of irradiation doses, 275 cGy irradiation with pMOG-BMT protected 100% of mice from EAE development even with two subsequent re-challenge with MOG. Irradiation doses <275 cGy produced dose dependent partial protection with significant disease protection still evident at 50 cGy. Splenocytes from 275 cGy recipients proliferated to MOG stimulation in vitro, indicating that MOG-reactive cells are present in the periphery but failed to induce disease. MOG-stimulated splenocytes produced little or no interleukin 17, interferon-gamma, granulocyte-monocyte colony stimulating factor and tumor necrosis factor-alpha compared with EAE control. Adoptive transfer of CD4 T cells from EAE-resistant mice into Rag2(-/-) mice devoid of MOG expression resulted in MOG-induced EAE in ~74% of mice. Treatment of EAE-resistant mice with anti programmed death 1 (PD-1) monoclonal antibody-induced EAE in 67% of mice. We conclude that non-myeloablative transplantation of self-antigen expressing BM induces robust peripheral tolerance that completely prevented EAE development. Our findings implicate clonal anergy and the PD-1 pathway in the maintenance of peripheral tolerance. PMID- 22071969 TI - Targeted cancer immunotherapy with oncolytic adenovirus coding for a fully human monoclonal antibody specific for CTLA-4. AB - Promising clinical results have been achieved with monoclonal antibodies (mAbs) such as ipilimumab and tremelimumab that block cytotoxic T lymphocyte-associated antigen-4 (CTLA-4, CD152). However, systemic administration of these agents also has the potential for severe immune-related adverse events. Thus, local production might allow higher concentrations at the target while reducing systemic side effects. We generated a transductionally and transcriptionally targeted oncolytic adenovirus Ad5/3-Delta24aCTLA4 expressing complete human mAb specific for CTLA-4 and tested it in vitro, in vivo and in peripheral blood mononuclear cells (PBMCs) of normal donors and patients with advanced solid tumors. mAb expression was confirmed by western blotting and immunohistochemistry. Biological functionality was determined in a T-cell line and in PBMCs from cancer patients. T cells of patients, but not those of healthy donors, were activated by an anti-CTLA4mAb produced by Ad5/3-Delta24aCTLA4. In addition to immunological effects, a direct anti-CTLA-4-mediated pro-apoptotic effect was observed in vitro and in vivo. Local production resulted in 43-fold higher (P<0.05) tumor versus plasma anti-CTLA4mAb concentration. Plasma levels in mice remained below what has been reported safe in humans. Replication-competent Ad5/3-Delta24aCTLA4 resulted in 81-fold higher (P<0.05) tumor mAb levels as compared with a replication-deficient control. This is the first report of an oncolytic adenovirus producing a full-length human mAb. High mAb concentrations were seen at tumors with lower systemic levels. Stimulation of T cells of cancer patients by Ad5/3-Delta24aCTLA4 suggests feasibility of testing the approach in clinical trials. PMID- 22071970 TI - In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression. AB - The efficient delivery of genetic material to the developing fetal brain represents a powerful research tool and a means to supply therapy in a number of neonatal lethal neurological disorders. In this study, we have delivered vectors based upon adenovirus serotype 5 (Ad5) and adeno-associated virus (AAV) pseudotypes 2/5, 2/8 and 2/9 expressing green fluorescent protein to the E16 fetal mouse brain. One month post injection, widespread caudal to rostral transduction of neural cells was observed. In discrete areas of the brain these vectors produced differential transduction patterns. AAV2/8 and 2/9 produced the most extensive gene delivery and had similar transduction profiles. All AAV pseudotypes preferentially transduced neurons whereas Ad5 transduced both neurons and glial cells. None of the vectors elicited any significant microglia-mediated immune response when compared with control uninjected mice. Whole-body imaging and immunohistological evaluation of brains 9 months post injection revealed long term expression using these non-integrating vectors. These data will be useful in targeting genetic material to discrete or widespread areas of the fetal brain with the purpose of devising therapies for early neonatal lethal neurodegenerative disease and for studying brain development. PMID- 22071971 TI - Physiological regulation of transgene expression by a lentiviral vector containing the A2UCOE linked to a myeloid promoter. AB - Protection against epigenetic silencing is a desirable feature of future gene therapy vectors, in particular for those applications in which transgene expression will not confer growth advantage to gene-transduced cells. The ubiquitous chromatin opening element (UCOE) consisting of the methylation-free CpG island encompassing the dual divergently transcribed promoters of the human HNRPA2B1-CBX3 housekeeping genes (A2UCOE) has been shown to shield constitutive active heterologous promoters from epigenetic modifications and chromosomal position effects. However, it is unclear if this element can be used to improve expression from tissue-specific enhancer/promoters, while maintaining tissue specificity in hematopoietic cells. Here, we evaluated the potential of the A2UCOE in combination with the myeloid-specific myeloid related protein 8 (MRP8) promoter to target transgene expression specifically to myeloid cells in vitro and in vivo from a self-inactivating lentiviral vector. The inclusion of the A2UCOE did not interfere with specific upregulation of MRP8 promoter activity during myeloid differentiation and mediated sustained and vector copy-dependent expression in myeloid cells. Notably, the A2UCOE did not protect the MRP8 promoter from methylation in the P19 embryonal carcinoma cell line, suggesting that this element maintains the inherent epigenetic state and transcriptional activity of cellular promoters in their native configuration. Thus, the A2UCOE could represent a useful protective genetic element in gene therapy vectors, ensuring physiological transcriptional regulation of tissue-specific promoters independent of the chromosomal integration site. PMID- 22071972 TI - Effect of topical interferon-gamma gene therapy using gemini nanoparticles on pathophysiological markers of cutaneous scleroderma in Tsk/+ mice. AB - Scleroderma is a chronic disorder manifested by excessive synthesis and deposition of collagen in skin and connective tissue, vascular abnormalities, and autoimmunity. Using microarray and real-time PCR data, we show that intradermally expressed interferon gamma (IFN-gamma), generated after intradermal injection of IFN-gamma-coding plasmid, and non-invasive topical nanoparticle (TNP) treatment with IFN-gamma-coding plasmid, decreased collagen synthesis (via the Jak/Stat 1 pathway), upregulated Th1 cytokine levels, and downregulated the profibrotic cytokine Transforming growth factor beta and the Smad pathways in the Tsk/+ (tight-skin scleroderma) mouse model. The TNP gene delivery system was constructed from gemini surfactant 16-3-16 and IFN-gamma-coding plasmid. Topical administration of IFN-gamma-coding plasmid in TNPs was effective in expressing IFN-gamma levels after a 20-day treatment regimen without increased TLR4, CCL2, CCL11 and CCR2 mRNA levels that were observed in injected animals, signs considered to be innate responses to injury. The more uniform transgene IFN-gamma expression caused significant (70-72%) collagen reduction, as assessed by reverse transcription real-time PCR. These results demonstrate efficient in vivo transfection using a gemini surfactant-based TNP delivery system able to modulate excessive collagen synthesis in scleroderma-affected skin. PMID- 22071973 TI - Gene transfer for ocular neovascularization and macular edema. AB - Diseases complicated by abnormal growth of vessels or excessive leakage are the most prevalent cause of moderate or severe vision loss in developed countries. Recent progress unraveling the molecular pathogenesis of several of these disease processes has led to new drug therapies that have provided major benefits to patients. However, those treatments often require frequent intraocular injections, and despite monthly injections, some patients have a suboptimal response. Gene transfer of antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization (NV) and/or excessive vascular leakage in the eye. Studies in animal models of ocular NV have demonstrated impressive results with a number of transgenes, and a clinical trial in patients with advanced neovascular age-related macular degeneration has provided proof-of-concept. Two ongoing clinical trials, one using an adeno-associated viral (AAV) vector to express a vascular endothelial growth factor-binding protein and another using a lentiviral vector to express endostatin and angiostatin, will provide valuable information that should help to inform future trials and provide a foundation on which to build. PMID- 22071974 TI - Preclinical safety evaluation of subretinal AAV2.sFlt-1 in non-human primates. AB - We report on the long-term safety of AAV2.sFlt-1 (a recombinant adeno-associated virus serotype 2 carrying the soluble form of the Flt-1 receptor) injection into the subretinal space of non-human primates. Levels of sFlt-1 protein were significantly higher (P<0.05) in the vitreous of four out of five AAV2.sFlt-1 injected eyes. There was no evidence of damage to the eyes of animals that received subretinal injections of AAV2.sFlt-1; ocular examination showed no anterior chamber flare, normal fundus and electroretinography responses equivalent to those observed before treatment. Notably, immunological analysis demonstrated that gene therapy involving subretinal injection of AAV2.sFlt-1 does not elicit cell-mediated immunity. Biodistribution analysis showed that AAV2.sFlt 1 could be detected only in the eye and not in the other organs tested. These data indicate that gene therapy with subretinal AAV2.sFlt-1 is safe and well tolerated, and therefore promising for the long-term treatment of neovascular diseases of the eye. PMID- 22071976 TI - Gene expression profiles in peripheral blood as a biomarker in cancer patients receiving peptide vaccination. AB - BACKGROUND: Because only a subset of patients show clinical responses to peptide based cancer vaccination, it is critical to identify biomarkers for selecting patients who would most likely benefit from this treatment. METHODS: The authors characterized the gene expression profiles in peripheral blood of vaccinated patients to identify biomarkers to predict patient prognosis. Peripheral blood was obtained from advanced castration-resistant prostate cancer patients, who survived for >900 days (long-term survivors, n = 20) or died within 300 days (short-term survivors, n = 20) after treatment with personalized peptide vaccination. Gene expression profiles in prevaccination and postvaccination peripheral blood mononuclear cells (PBMCs) were assessed by DNA microarray. RESULTS: There were no statistically significant differences in the clinical or pathological features between the 2 groups. Microarray analysis of prevaccination PBMCs identified 19 genes that were differentially expressed between the short term and long-term survivors. Among the 15 up-regulated genes in the short-term survivors, 13 genes, which were also differentially expressed in postvaccination PBMCs, were associated with gene signatures of granulocytes. When a set of 4 differentially expressed genes were selected as the best combination to determine patient survival, prognosis was correctly predicted in 12 of 13 patients in a validation set (accuracy, 92%). CONCLUSIONS: These results suggested that abnormal granulocytes present in the PBMC faction may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination. Gene expression profiling in peripheral blood might thus be informative for devising better therapeutic strategies by predicting patient prognosis after cancer vaccines. PMID- 22071978 TI - Therapeutics. Another tool in the BCR-ABL kit? PMID- 22071977 TI - An intermittent approach for cancer chemoprevention. AB - Cancer chemoprevention approaches generally use long-term, continuous treatment, which can produce major preventive effects but which can also have unexpected serious adverse events. This raises the question of whether intermittent dosing schedules might reduce toxicity while retaining benefit, a concept that we call short-term intermittent therapy to eliminate premalignancy (SITEP). Recent preclinical studies support a novel SITEP approach whereby short-term, intermittent therapy eliminates premalignant cells via apoptosis that is induced by synthetic lethal interactions. Synthetic lethality allows personalized, selective elimination of premalignant clones without harming normal cells. This Opinion article provides a detailed discussion of the principle, method and future development of the SITEP approach. PMID- 22071979 TI - Kidney tumours. 'NRF said. PMID- 22071980 TI - Synthesis of luminescent homo-dinuclear cationic lanthanide cyclen complexes bearing amide pendant arms through the use of copper catalysed (1,3-Huisgen, CuAAC) click chemistry. AB - The design and synthesis of dinuclear-lanthanide complexes possessing triazole based bridges, formed by using copper catalysed 1,3-cycloaddition reactions between heptadentate alkyne functionalised cyclen europium or terbium complexes and di-azides (CuAAC reactions), are described. While this click reaction worked well for the formation of the homo-Eu(III) and Tb(III) bis-tri-arm cyclen N,N dimethyl acetamide complexes, 2Eu and 2Tb, and for the homo-Eu(III) chiral N methylnaphthalene based complexes 3Eu (S,S,S) and 4Eu (R,R,R), the formation of the Eu(III) complex of the primary amide analogue of 2, namely 1Eu, was not successful, clearly demonstrating the effect that the nature of the pendant arms has on this reaction. Furthermore, the click reactions between the free alkyne cyclen bis-derivatives (5-8) and the di-azide were unsuccessful, most likely due to the high affinity of the cyclen macrocycles for Cu(II). The Eu(III) complexes of 2-4 and 2Tb all gave rise to sensitised metal ion centred emission upon excitation of the triazole or the naphthalene antennae in methanol solution, and their hydration states were determined, which showed that while the Eu(III) mono nuclear complexes had q ~ 2, the click products all had q ~ 1. In the case of 3Eu (S,S,S) and 4Eu (R,R,R), the circular polarised emission (CPL) was also observed for both, demonstrating the chiral environment of the lanthanide centres. PMID- 22071982 TI - The effect of span length of flexural testing on properties of short fiber reinforced composite. AB - The aim of this study was to determine the effect of different span lengths of flexural testing on some properties of test specimens made of experimental short fiber reinforced composite resin (FC). Bar shaped specimens with different lengths were made from experimental FC composite with an average fiber length of 3 mm and particulate filler composite (PFC, control: Z250). The specimens (n = 8) were polymerized with a hand light-curing unit for 40 s and dry stored in a room temperature for 24 h before testing. Three-point flexural test for determination of ultimate flexural strength, toughness and flexural modulus of specimens was made with different span lengths (20, 15, 10, 7, 6, 5 mm) with a speed of 1.0 mm/min until fracture. By shortening the span length for specimens made of FC or PFC, the flexural modulus decreased (from ca. 11 to 4 GPa) and flexural toughness increased (from ca. 0.25 to 2.25 MPa). Reduction in flexural strength by shortening the span length was found with PFC (from 170 to 125 MPa) but not with FC, which showed reduction by span lengths from 20 to 7 mm and considerable increase of flexural strength by further shortening the span length from 7 to 5 mm. Shortening of span length of flexural testing showed linear reduction of the measured and calculated flexural properties of PFC and some properties of FC, but flexural strength values for FC were non-linearly related to the span length: the highest values were obtained with the longest and the shortest span lengths. In reporting the flexural values of composites, the span length-specimen dimension ratio, and the length of the reinforcement need to be taken into consideration. PMID- 22071981 TI - Immortalized gingival fibroblasts as a cytotoxicity test model for dental materials. AB - In vitro cytotoxicity test is an initial step to identify the harmful effects of new dental materials. Aim of this study was to develop a stable human cell line derived from normal gingival fibroblasts (hNOF) and to assess its feasibility in in vitro cytotoxicity testing. Immortalized human gingival fibroblasts (hTERT hNOF) were successfully established with human telomerase reverse transcriptase gene transfection, preserving its phenotypical characteristics, replicative potential and biological properties. Utilizing standard cytotoxicity test modeling and dental materials, hTERT-hNOF were evaluated for their feasibility in cytotoxicity testing, compared with hNOF and L929 cells. Similar pattern of cytotoxic response was observed among hNOF, hTERT-hNOF and L929 cells. Cytotoxicity response of hTERT-hNOF was significantly similar to hNOF, moreover hTERT-hNOF and hNOF were found to be more sensitive towards the tested dental materials compared to L929 cells. This study suggested that hTERT-hNOF is an effective cytotoxic test model for dental materials. PMID- 22071983 TI - An innovative multi-component variate that reveals hierarchy and evolution of structural damage in a solid: application to acrylic bone cement. AB - A major limitation of solid mechanics is the inability to take into account the influence of hierarchy and evolution of the inherent microscopic structure on evaluating the performance of materials. Irreversible damage and fracture in solids, studied commonly as cracks, flaws, and conventional material properties, are by no means descriptive of the subsequent responses of the microstructures to the applied load. In this work, we addressed this limitation through the use of a novel multi-component variate. The essence of this variate is that it allows the presentation of the random damage in the amplitude spectrum, probability space, and probabilistic entropy. Its uniqueness is that it reveals the evolution and hierarchy of random damage in multi- and trans-scales, and, in addition, it includes the correlations among the various damage features. To better understand the evolution and hierarchy of random damage, we conducted a series of experiments designed to test three variants of a poly (methyl methacrylate) (PMMA) bone cement, distinguished by the methods used to sterilize the cement powder. While analysis of results from conventional tension tests and scanning electron microscopy failed to pinpoint differences among these cement variants, our multi-component variate allowed quantification of the multi- and trans-scale random damage events that occurred in the loading process. We tested the statistical significance of damage states to differentiate the responses at the various loading stages and compared the damage states among the groups. We also interpreted the hierarchical and evolutional damage in terms of the probabilistic entropy (s), the applied stress (sigma), and the trajectory of damage state. We found that the cement powder sterilization method has a strong influence on the evolution of damage states in the cured cement specimens when subjected to stress in controlled mechanical tests. We have shown that in PMMA bone cements, our damage state variate has the unique ability to quantify and discern the history and evolution of microstructural damage. PMID- 22071984 TI - Compatibility of different polymers for cord blood-derived hematopoietic progenitor cells. AB - The low yield of hematopoietic progenitor cells (HPC) present in cord blood grafts limits their application in clinics. A reliable strategy for ex vivo expansion of functional HPC is a present goal in regenerative medicine. Here we evaluate the capacity of several two-dimensional polymers to support HPC proliferation. Basic compatibility was tested by measuring cell viability, cytotoxicity and apoptosis of CD34(+) progenitors that were short and long-term exposed to sixteen bio and synthetic polymers. Resomer((r)) RG503, PCL and Fibrin might be good alternatives to tissue culture plastic for culture of CB-derived CD34(+) progenitors. Further, these polymers will be produced in three dimensional structures and tested for their cytocompatibility. PMID- 22071986 TI - Synthesis of nucleoside mono- and triphosphates bearing oligopyridine ligands, their incorporation into DNA and complexation with transition metals. AB - Modified nucleoside mono- (dA(R)MPs and dC(R)MPs) and triphosphates (dA(R)TPs and dC(R)TPs) bearing bipyridine or terpyridine ligands attached via acetylene linker were prepared by single-step aqueous-phase Sonogashira cross-coupling of 7-iodo-7 deaza-dAMP or -dATP, and 5-iodo-dCMP or -dCTP with the corresponding bipyridine- or terpyridine-linked acetylenes. The modified dN(R)TPs were successfully incorporated into the oligonucleotides by primer extension experiment (PEX) using different DNA polymerases and the PEX products were used for post-synthetic complexation with Fe(2+). PMID- 22071985 TI - Characterization of bionanocomposite scaffolds comprised of mercaptoethylamine functionalized gold nanoparticles crosslinked to acellular porcine tissue. AB - Bionanocomposite scaffolds comprised of nanomaterials and the extracellular matrix (ECM) of porcine diaphragm tissue capitalizes on the benefits of utilizing a natural ECM material, while also potentially enhancing physicomechanical properties and biocompatibility through nanomaterials. Gold nanoparticle (AuNP) bionanocomposite scaffolds were subjected to a number of characterization techniques to determine whether the fabrication process negatively impacted the properties of the porcine diaphragm tissue and whether the AuNP improved the properties of the tissue. Tensile testing and differential scanning calorimetry demonstrated that the bionanocomposite possessed improved tensile strength and thermal stability relative to natural tissue. The collagenase assay and Fourier transform infrared spectroscopy additionally confirmed that denaturation of the collagen of the ECM did not occur. The novel bionanocomposite scaffold possessed properties similar to commercially available scaffolds and will be further developed for soft tissue applications such as hernia repair through in vivo studies in an animal model. PMID- 22071987 TI - The Twister laser fiber degradation and tissue ablation capability during 980-nm high-power diode laser ablation of the prostate. A randomized study versus the standard side-firing fiber. AB - The objective of this work is to test the ablation capability and fiber degradation of the novel Twister fibers (TW), in both the large (LTW) and the standard (STW) sizes, against the standard side-firing (SF) fiber in a clinical setting during the treatment of BPH patients using the 980-nm high-power diode laser (HPDL). One hundred and twenty BPH patients treated with HPDL (Ceralase300, Biolitec AG, Jena, Germany) were randomized to receive treatment by one of the three fibers. Operative time corrected to tissue volume, laser treatment time, and laser energy were measured. Ablation rate was calculated as follows: the decrease of the prostate volume after 6 months/laser time. The fibers' resistance to degradation was defined by the laser energy needed to degrade the fiber completely. Preoperative prostate volume of 76 +/- 38, 70 +/- 39, and 88 +/- 49 cc decreased by 49 +/- 16, 51 +/- 20, and 63 +/- 16% for the SF, STW, and LTW fibers, respectively. This difference was highly significant when the LTW was compared to the other two fibers (p < 0.001). Prostate volume reduction post operatively within each group as compared to the pre-operative volume was highly significant (p < 0.001). The ablation rate was highest in LTW, being 1.31 +/- 0.59, 1.09 +/- 0.51, and 1.54 +/- 0.44 cc/min for the SF, STW, and LTW fibers, respectively. The LTW fiber resisted degradation more than the other fibers and the STW more than the SF fiber (p < 0.001). This study demonstrates the higher ablation efficiency and resistance to degradation of the LTW fiber as compared to the STW and SF fibers. The STW fiber has a similar ablation rate of the SF fiber but resists degradation better. PMID- 22071988 TI - Body integrity identity disorder: from a psychological to a neurological syndrome. AB - Body Integrity Identity Disorder (BIID) is a condition in which individuals experience an intense desire for amputation of an healthy limb. Recently, McGeoch and colleagues provided the first direct evidence that this syndrome may be neurological rather than psychological in its origin. However, before including BIID in body ownership disorders, several concerns should be clarified, exploring other components of body representation and not only somatosensory perception. PMID- 22071989 TI - Rapamycin inhibits osteoclast formation in giant cell tumor of bone through the C/EBPbeta - MafB axis. AB - Giant cell tumor (GCT) of bone is a benign type of tumor, but the presence of hyperactive multinucleated giant osteoclasts cause local osteolytic lesions, increasing morbidity in patients. To specifically target hyperactive multinucleated giant osteoclasts in GCTs, one would envisage the usage of osteoclast inhibitors or genetic modulation of osteoclastogenesis. Recently, we have found that the translationally regulated balance between the transcription factor C/EBPbeta long (LAP) and short (LIP) protein isoforms regulates osteoclast differentiation. Here, we report that GCTs express high levels of the LIP C/EBPbeta isoform, which in mice cause giant osteoclast formation. In mice, inhibition of mTOR activity by rapamycin decreased osteoclast differentiation by shifting the alternative translation initiation of C/EBPbeta isoforms towards LAP. Similarly, rapamycin treatment of GCT cell cultures derived from seven different patients strongly reduced formation of giant osteoclasts and bone resorption. This was accompanied by an increase in MafB, previously shown to be the mediator of the effect of rapamycin on osteoclast differentiation in mice. These data suggest that C/EBPbeta is a determinant of giant osteoclast formation in GCT and that pharmacological adjustment of the C/EBPbeta isoform ratio could serve as a potential novel therapeutic approach. PMID- 22071991 TI - [Viennese Clinical Weekly: foreword]. PMID- 22071993 TI - Introduction to the Canadian Forces operational medicine supplement. PMID- 22071994 TI - Surgical experience at the Canadian-led Role 3 Multinational Medical Unit in Kandahar, Afghanistan. AB - INTRODUCTION: The purpose of this study was to document the surgical experience of the Role 3 Multinational Medical Unit (R3MMU) at Kandahar Airfield Base while Canada was the lead nation for the facility. This study will help inform on future staffing, training, and deployment issues of field hospitals on military missions. METHODS: From February 2, 2006, to October 15, 2009, the Canadian Forces Health Services served as the lead nation for the R3MMU. We retrospectively reviewed the electronic and the actual operative database during this timeframe to assess surgical workload, types of surgical procedures performed, and the involved anatomic regions of the surgical procedures. RESULTS: During this timeframe, there were 6,735 operative procedures performed on 4,434 patients. The majority of our patients were Afghan nationals, with Afghan civilians representing 34.8%, Afghan National Security Forces 31.6%, and North Atlantic Treaty Organization forces 25.3%. The number of operative procedures by specialty were 3,329 in orthopedic surgery (49.4%), 2,053 general surgery (30.5%), 930 oral maxillofacial surgery (13.8%), and 272 neurosurgery (6%). The most frequently operated on body region was the soft tissue, followed by the extremities and then the abdomen. Thoracic operations were very infrequent. CONCLUSION: Our operative data were slightly different from historical controls. Hopefully, this data will help with planning for future deployments of field hospitals on military missions. PMID- 22071995 TI - Causes of death in Canadian Forces members deployed to Afghanistan and implications on tactical combat casualty care provision. AB - BACKGROUND: As part of its contribution to the Global War on Terror and North Atlantic Treaty Organization's International Security Assistance Force, the Canadian Forces deployed to Kandahar, Afghanistan, in 2006. We have studied the causes of deaths sustained by the Canadian Forces during the first 28 months of this mission. The purpose of this study was to identify potential areas for improving battlefield trauma care. METHODS: We analyzed autopsy reports of Canadian soldiers killed in Afghanistan between January 2006 and April 2008. Demographic characteristics, injury data, location of death within the chain of evacuation, and cause of death were determined. We also determined whether the death was potentially preventable using both explicit review and implicit review by a panel of trauma surgeons. RESULTS: During the study period, 73 Canadian Forces members died in Afghanistan. Their mean age was 29 (+/-7) years and 98% were male. The predominant mechanism of injury was explosive blast, resulting in 81% of overall deaths during the study period. Gunshot wounds and nonblast related motor vehicle collisions were the second and third leading mechanisms of injury causing death. The mean Injury Severity Score was 57 (+/-24) for the 63 study patients analyzed. The most common cause of death was hemorrhage (38%), followed by neurologic injury (33%) and blast injuries (16%). Three deaths were deemed potentially preventable on explicit review, but implicit review only categorized two deaths as being potentially preventable. CONCLUSIONS: The majority of combat-related deaths occurred in the field (92%). Very few deaths were potentially preventable with current Tactical Combat Casualty interventions. Our panel review identified several interventions that are not currently part of Tactical Combat Casualty that may prevent future battlefield deaths. PMID- 22071996 TI - Needle decompression for tension pneumothorax in Tactical Combat Casualty Care: do catheters placed in the midaxillary line kink more often than those in the midclavicular line? AB - BACKGROUND: Tactical Combat Casualty Care (TCCC) is a system of prehospital trauma care designed for the combat environment. Needle decompression (ND) is a critical TCCC intervention, because previous data suggest that up to 33% of all preventable deaths on the battlefield result from tension pneumothoraces. There has recently been increased interest in performing ND at the fifth intercostal space in the midaxillary line to prevent complications associated with landmarking second intercostal space in the midclavicular line site. We developed a model to assess whether catheters placed in the midaxillary line for decompressing tension pneumothoraces are more prone to kinking than those placed in the midclavicular line because of adducted arms during military transport. METHODS: To simulate ND, we secured segments of porcine chest walls over volunteer soldiers' chests and placed 14-gauge, 1.5-inch angiocatheters through the porcine wall segments which were affixed to either the midaxillary or midclavicular location on the volunteers. We then assessed for occlusion and kinking by flow of normal saline (NS) through the angiocatheter in situ. The angiocatheter was then transduced using standard arterial line manometry, and the opening pressures required to initiate flow through the catheters were measured. The opening pressures were then converted to mm Hg. We also assessed for catheter occlusion after the physical manipulation of the patient, by simulated patient transport. RESULTS: We observed that there was a significant pressure difference required to achieve free flow through the in situ angiocatheter between the fifth intercostal space midaxillary line versus the second intercostal space midclavicular line site (13.1 +/- 3.6 mm Hg vs. 7.9 +/- 1.8 mm Hg). CONCLUSIONS: This study suggests that the 14-gauge, 1.5-inch angiocatheter used for ND in the midaxillary line may partially and temporarily occlude in patients who will be transported on military stretchers. The pressure of 12.8 mm Hg has been documented in animal models as the pressure at which hemodynamic instability develops. This may contribute to the reaccumulation of tension pneumothoraces and ultimate patient deterioration in military transport. PMID- 22071997 TI - Spinal injuries after improvised explosive device incidents: implications for Tactical Combat Casualty Care. AB - BACKGROUND: Tactical Combat Casualty Care aims to treat preventable causes of death on the battlefield but deemphasizes the importance of spinal immobilization in the prehospital tactical setting. However, improvised explosive devices (IEDs) now cause the majority of injuries to Canadian Forces (CF) members serving in Afghanistan. We hypothesize that IEDs are more frequently associated with spinal injuries than non-IED injuries and that spinal precautions are not being routinely employed on the battlefield. METHODS: We examined retrospectively a database of all CF soldiers who were wounded and arrived alive at the Role 3 Multinational Medical Unit in Kandahar, Afghanistan, from February 7, 2006, to October 14, 2009. We collected data on demographics, injury mechanism, anatomic injury descriptions, physiologic data on presentation, and prehospital interventions performed. Outcomes were incidence of any spinal injuries. RESULTS: Three hundred seventy-two CF soldiers were injured during the study period and met study criteria. Twenty-nine (8%) had spinal fractures identified. Of these, 41% (n = 12) were unstable, 31% (n = 9) stable, and 28% indeterminate. Most patients were injured by IEDs (n = 212, 57%). Patients injured by IEDs were more likely to have spinal injuries than those injured by non-IED-related mechanisms (10.4% vs. 2.3%; p < 0.01). IED victims were even more likely to have spinal injuries than patients suffering blunt trauma (10.4% vs. 6.7%; p = 0.02). Prehospital providers were less likely to immobilize the spine in IED victims compared with blunt trauma patients (10% [22 of 212] vs. 23.0% [17 of 74]; p < 0.05). CONCLUSIONS: IEDs are a common cause of stable and unstable spinal injuries in the Afghanistan conflict. Spinal immobilization is an underutilized intervention in the battlefield care of casualties in the conflict in Afghanistan. This may be a result of tactical limitations; however, current protocols should continue to emphasize the judicious use of immobilization in these patients. PMID- 22071998 TI - Design and preliminary results of a pilot randomized controlled trial on a 1:1:1 transfusion strategy: the trauma formula-driven versus laboratory-guided study. AB - BACKGROUND: Retrospective reviews have recently shown an survival benefit for adopting a resuscitation strategy that transfuses plasma and platelets at a near 1:1 ratio with red blood cells (RBCs). However, a randomized controlled trial on the topic is lacking. We report on the design and preliminary results of our ongoing randomized control pilot trial (ClinicalTrial.gov NCT00945542). METHODS: This is a 2-year feasibility randomized control trial at a single tertiary trauma center. Bleeding trauma patients were randomized to either a laboratory-driven or a formula-driven (1 plasma:1 platelet:1 RBC) transfusion protocols. Feasibility was assessed by analyzing for ability to enroll patients, appropriate activation of transfusion protocols, time to transfusion of each type of blood product, laboratory turnaround time, ratio of blood products transfused, and wastage of blood products. RESULTS: From July 6, 2009, to May 31, 2010, n = 18 patients were randomized and included in the study. Issues that we noted were the need to do postrandomization exclusions, the need to have rapid and accurate predictors of massive bleeding to enroll patients quickly, and the need to have waived consent for study participation. As well, we noted that the logistics of administering 1:1:1 were formidable and required rapid access to thawed plasma. Similarly, challenges in the control arm of such a study included the turnaround time for obtaining laboratory results. CONCLUSION: Despite major challenges, our initial experience suggests that with an organized system, it is possible to prospectively randomize massively bleeding trauma patients. The accomplishment of high ratios of plasma to RBCs is challenging with current thawing methods and unavailability of thawed plasma in Canada. Longer shelf-life for plasma and faster plasma thawing microwaves should overcome some of these obstacles. For a laboratory-guided transfusion protocol, massive transfusion protocols should be in place with faster turnaround time for coagulation tests. Finally, further research on predictors of massive transfusion is needed. PMID- 22072000 TI - Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity. AB - BACKGROUND: Recent studies have shown that acute traumatic coagulopathy is associated with hypoperfusion, increased plasma levels of soluble thrombomodulin, and decreased levels of protein C but with no change in factor VII activity. These findings led to the hypothesis that acute traumatic coagulopathy is primarily due to systemic anticoagulation, by activated protein C, rather than decreases in serine protease activity. This study was designed to examine the effect of hypoperfusion secondary to traumatic injury on the activity of coagulation factors. METHODS: Post hoc analysis of prospectively collected data on severely injured adult trauma patients presenting to a single trauma center within 120 minutes of injury. Venous blood was analyzed for activity of factors II, V, VII, VIII, IX, X, and XI. Base deficit from arterial blood samples was used as a marker of hypoperfusion. RESULTS: Seventy-one patients were identified. The activity of factors II, V, VII, IX, X, and XI correlated negatively with base deficit, and after stratification into three groups, based on the severity of hypoperfusion, a statistically significant dose-related reduction in the activity of factors II, VII, IX, X, and XI was observed. Hypoperfusion is also associated with marked reductions in factor V activity levels, but these appear to be relatively independent of the degree of hypoperfusion. The activity of factor VIII did not correlate with base deficit. CONCLUSIONS: Hypoperfusion in trauma patients is associated with a moderate, dose-dependent reduction in the activity of coagulation factors II, VII, IX, X, and XI, and a more marked reduction in factor V activity, which is relatively independent of the severity of shock. These findings suggest that the mechanisms underlying decreased factor V activity -which could be due to activated protein C mediated cleavage, thus providing a possible link between the proposed thrombomodulin/thrombin-APC pathway and the serine proteases of the coagulation cascade--and the reductions in factors II, VII, IX, X, and XI may differ. Preservation of coagulation factor activity in the majority of normally and moderately hypoperfused patients suggests that aggressive administration of plasma is probably only indicated in severely hypoperfused patients. Markers of hypoperfusion, such as base deficit, might be better and more readily available predictors of who require coagulation support than international normalized ratio or activated partial thromboplastin time. PMID- 22071999 TI - Clotting factor deficiency in early trauma-associated coagulopathy. AB - BACKGROUND: Coagulopathic bleeding is a leading cause of in-hospital death after injury. A recently proposed transfusion strategy calls for early and aggressive frozen plasma transfusion to bleeding trauma patients, thus addressing trauma associated coagulopathy (TAC) by transfusing clotting factors (CFs). This strategy may dramatically improve survival of bleeding trauma patients. However, other studies suggest that early TAC occurs by protein C activation and is independent of CF deficiency. This study investigated whether CF deficiency is associated with early TAC. METHODS: This is a prospective observational cohort study of severely traumatized patients (Injury Severity Score >= 16) admitted shortly after injury, receiving minimal fluids and no prehospital blood. Blood was assayed for CF levels, thromboelastography, and routine coagulation tests. Critical CF deficiency was defined as <= 30% activity of any CF. RESULTS: Of 110 patients, 22 (20%) had critical CF deficiency: critically low factor V level was evident in all these patients. International normalized ratio, activated prothrombin time, and, thromboelastography were abnormal in 32%, 36%, and 35%, respectively, of patients with any critically low CF. Patients with critical CF deficiency suffered more severe injuries, were more acidotic, received more blood transfusions, and showed a trend toward higher mortality (32% vs. 18%, p = 0.23). Computational modeling showed coagulopathic patients had pronounced delays and quantitative deficits in generating thrombin. CONCLUSIONS: Twenty percent of all severely injured patients had critical CF deficiency on admission, particularly of factor V. The observed factor V deficit aligns with current understanding of the mechanisms underlying early TAC. Critical deficiency of factor V impairs thrombin generation and profoundly affects hemostasis. PMID- 22072001 TI - Disseminated intravascular coagulopathy in the first 24 hours after trauma: the association between ISTH score and anatomopathologic evidence. AB - BACKGROUND: Recent studies questioned "classical" concepts in trauma care, including whether disseminated intravascular coagulation (DIC) occurs in trauma. The knowledge on trauma DIC is limited to few studies built on diagnosing DIC with laboratory-based scores. This study explores whether DIC diagnosed by the well-established ISTH (International Society for Thrombosis and Hemostasis) score is corroborated by anatomopathologic findings. METHODS: Prospective observational cohort study of severely injured (ISS >= 16) patients. DIC was diagnosed by the ISTH score throughout the first 24 hours after trauma. All organs surgically removed within 24 hours of trauma were reviewed by two independent pathologists. All autopsy reports were reviewed. RESULTS: Of 423 patients enrolled, ~11% had "overt DIC" and 85% had "suggestive of non-overt DIC" scores throughout the 24 hours after trauma. "Overt DIC" patients had higher mortality and worse bleeding, receiving more blood and plasma transfusions. One hundred and sixteen patients underwent surgery within 24 hours of trauma, and all 40 excised organs were reviewed by two pathologists. Twenty-seven autopsies reports were reviewed. No anatomopathologic evidence of DIC was identified in the first 24 hours, even after additional histochemical staining. d-dimer was universally elevated after trauma. Common DIC features: platelet count, fibrinogen, clotting time, and factor VIII drop were mostly absent. CONCLUSIONS: d-dimer has a disproportional participation in trauma DIC scores. Within 24 hours of trauma, most severely injured patients have DIC scores "suggestive for" or of "overt DIC" but no anatomopathologic evidence of DIC. Considering pathologic findings as the gold standard diagnosis, then DIC is exceptionally uncommon and the ISTH score should not be used for trauma. PMID- 22072002 TI - The natural history of trauma-related coagulopathy: implications for treatment. AB - BACKGROUND: Hemorrhage is a leading cause of death in trauma patients and coagulopathy is a significant contributor. Although the exact mechanisms of trauma-associated coagulopathy (TAC) are incompletely understood, hemostatic resuscitation strategies have been developed to treat TAC. Our study sought to identify which trauma patients develop TAC and the factors associated with its development, to describe the natural history of TAC, and to identify patients with TAC who may not require hemostatic resuscitation. METHODS: Patients with early coagulopathy (International Normalized Ratio >1.3) who were admitted directly from the scene within 1 hour of injury were identified in our institutional trauma registry. We analyzed these data for the presence of TAC, predictors of early and delayed TAC, and evolution of TAC during the first 24 hours of admission. RESULTS: Of 2,473 patients, 290 (12%) had early TAC (International Normalized Ratio >1.3) and 271 (11%) developed delayed TAC. Multivariate analysis identified female gender (odds ratio [OR] 1.25 [1.11 1.41]), lower pH (OR 0.08 [0.015-0.47]), lower hemoglobin (OR 0.96 [0.95-0.97]), lower temperature (OR 0.82 [0.70-0.95]), and blunt mechanism (OR 0.49 [0.33 0.71]) as factors significantly associated with development of early TAC. Progression of early TAC occurred in 64%, and these patients had more severe abdominal injury and received more emergency room crystalloid. Of patients with early TAC who did not receive fresh frozen plasma, only 49% developed worsening coagulopathy. Patients with isolated intracranial hemorrhage had higher rates of bleeding progression (75% vs. 20%, p < 0.005) in the presence of early TAC. CONCLUSIONS: TAC may appear in an early or delayed form and its presence and progression are associated with a number of identifiable factors. Although TAC commonly progresses, it also resolves spontaneously in many patients. Further research is required to identify which patients with TAC require hemostatic treatment, although those with intracranial hemorrhages seem to warrant aggressive therapy. PMID- 22072003 TI - Recombinant human erythropoietin improves gut barrier function in a hemorrhagic shock and resuscitation rat model. AB - BACKGROUND: Gut injury and bacterial translocation develop and persist after limited periods of hemorrhagic shock. Erythropoietin (EPO) can exert hemodynamic, anti-inflammatory, and tissue protective effects. We tested the hypothesis that EPO given at the time of resuscitation with saline will reduce functional ileal injury 24 hours after shock. METHODS: Sprague-Dawley rats (n = 6 per group) were randomized to sham surgery or hemorrhagic shock maintained at mean arterial pressure 40 mm Hg for 60 minutes and then treated with either saline resuscitation (three times the volume of shed blood) or saline + recombinant human EPO (rHuEPO) resuscitation. Intravenous rHuEPO (1,000 U/kg) was given at the start of saline resuscitation, and at 24 hours ileal function was evaluated using quantitative cultures of mesenteric lymph nodes to assess for bacterial translocation (colony-forming units per gram of tissue [CFU/g]), determination of portal vein plasma endotoxin levels and histopathological evaluation using semi thin plastic sections of the distal ileum. In a second series of animals, fluorescein isothiocyanate-dextran 4000 (FD-4) was used to assess mucosal permeability of the distal ileum to macromolecules. RESULTS: At 24 hours, the saline group had morphologic evidence of intestinal injury when compared with the sham group, and the degree of mucosal injury was less in the saline + rHuEPO when compared with the saline group, which demonstrated significantly reduced bacterial translocation to the mesenteric lymph nodes (383 CFU/g +/- 111 CFU/g vs. 1130 CFU/g +/- 297 CFU/g; p < 0.05) and decreased terminal ileum permeability to FD-4 (3.08 MUg/mL +/- 0.31 MUg/mL vs. 5.14 MUg/mL +/- 0.88 MUg/mL; p < 0.05). No significant difference was found in the portal vein endotoxin levels between the two groups. Histopathological evaluation demonstrated a trend for decreased enterocyte disarray or disruption and vacuolization in the saline + rHuEPO versus saline group. CONCLUSION: Using rHuEPO at time of saline resuscitation resulted in decreased bacterial translocation and permeability to macromolecules 24 hours after shock. These observations suggest that rHuEPO can mediate a protective effect on intestinal mucosal barrier function during ischemic injury. PMID- 22072004 TI - Erythropoietin improves skeletal muscle microcirculation through the activation of eNOS in a mouse sepsis model. AB - BACKGROUND: Sepsis and septic shock remain the major causes of morbidity and mortality in intensive care units. One mechanism that leads to organ failure is microcirculatory dysfunction. Erythropoietin (EPO) is a glycoprotein produced by the kidney that primarily regulates erythropoiesis, but it also can exert hemodynamic, anti-inflammatory, and tissue protective effects. We previously reported that administration of EPO to septic mice improves mouse skeletal muscle capillary perfusion and tissue bioenergetics. The objective of this study was to explore the potential mechanism(s) involved. METHODS: Sepsis was induced by intraperitoneal (i.p.) injection of a fecal suspension (12.5 g in 0.5 saline/mouse) in mice. At 18 hours after sepsis induction, a single dose of rHuEPO (400 U/kg) was given to the mice. Mouse capillary perfusion density and nicotinamide adenine dinucleotide (NADH) fluorescence in skeletal muscle were observed using intravital microscopy. Endothelial cells derived from the skeletal muscle were treated with rHuEPO (5 U/mL) and endothelial nitric oxide synthase (eNOS) activation and activity were assessed. RESULTS: Septic mice had decreased capillary perfusion density and increased tissue NADH fluorescence indicating impaired tissue bioenergetics, whereas animals treated with rHuEPO demonstrated an improvement in capillary perfusion density and decreased skeletal muscle NADH fluorescence. The beneficial effect of rHuEPO did not occur in septic mice treated with l-NAME (an NOS inhibitor, 20 mg/kg) or mice genetically deficient in eNOS. Treatment of endothelial cells with rHuEPO resulted in activation of eNOS as indicated by increased eNOS phosphorylation and NO production. CONCLUSIONS: Our results suggest that eNOS plays an important role in mediating the beneficial effect of rHuEPO on microcirculation in this septic mouse model. PMID- 22072005 TI - The use of the radiographic appearance of the azygos vein to assess volume status in trauma patients. AB - BACKGROUND: The assessment of hypovolemia in victims of trauma is a critical aspect of resuscitation and care in the initial presentation of a patient. This study attempted to validate the use of the appearance of the azygos vein (AV) on initial chest radiographs as a parameter that may add to this initial assessment. METHODS: The design involved a blinded independent assessment of serial chest radiographs from consecutive trauma cases from January 21, 2008, until September 13, 2008, by a trained Radiologist and a Trauma Team Leader (TTL) and then comparing this assessment to mean arterial pressure (MAP) and heart rate estimates of volume status in serial severe trauma patients. This is an insensitive but specific measure of volume status. RESULTS: In this population with high prevalence of hypovolemia, the presence of an AV <= 0.5 cm yielded a sensitivity of 4.9% and 9.8% for the TTL and Radiologist, respectively, in patients with a mean arterial pressure <70 and heart rate >100. The specificity was 98.8% and 91.6%, which translates into a positive likelihood ratio of 4.08 and 1.17 for the TTL and Radiologist, respectively. The Kappa score for agreement between the two readers was 0.4. CONCLUSION: When a small AV can be seen by the TTL, it may be a useful adjunct to the assessment of volume status. PMID- 22072006 TI - Controlled blast exposure during forced explosive entry training and mild traumatic brain injury. AB - BACKGROUND: There is a paucity of data regarding the pathophysiology and short- and long-term neurologic consequences of primary blast injury in humans. The purpose of this investigation was to test the feasibility of implementing a research protocol in the context of a forced explosive entry training course. METHODS: Instructors (n = 4) and students (n = 10) completing the Police Explosives Technicians-Forced Entry Instructors course were recruited to participate in the study. Participants underwent a physical examination, tests of postural stability and vestibular ataxia, and a neurocognitive battery 1 day before and 10 days following practical forced explosive entry exercises. RESULTS: The instructors reported significantly more blast exposures in their careers than the students (p < 0.05). Seventy-five percent of the instructors and 50% of the students reported a history of trauma to the head. A minority of the participants had deficits on cranial nerve, vestibular ataxia, and neurocognitive tests which did not change significantly postexposure. All the instructors and most of the students (90%) demonstrated postural stability deficits at baseline which did not change significantly postexposure. CONCLUSIONS: Studying the effects of blast exposure on the human brain in a controlled experimental setting is not possible. Forced explosive entry training courses afford an opportunity to begin examining this issue in real time in a controlled setting. This study underscores the importance of baseline testing of troops, of the consideration of subclinical implications of blast exposure, and of continued studies of the effects of blast exposures, including repeated exposures on the human brain. PMID- 22072007 TI - The value of serum biomarkers in prediction models of outcome after mild traumatic brain injury. AB - BACKGROUND: To determine, using a civilian model of mild traumatic brain injury (TBI), the added value of biomarker sampling upon prognostication of outcome at 1 week and 6 weeks postinjury. METHODS: The Galveston Orientation and Amnesia test was administered, and blood samples for serum protein S100B and neuron-specific enolase (NSE) were collected from 141 emergency department patients within 4 hours of a suspected mild TBI (mTBI). The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) was administered via telephone 3 days postinjury. Patients were assessed by a physician at 1 week (n = 113; 80%) and 6 weeks (n = 95; 67%) postinjury. Neurocognitive and postural stability measures were also administered at these follow-ups. RESULTS: Levels of S100B and NSE were found to be abnormally elevated in 49% and 65% of patients with TBI, respectively. Sixty-eight percent and 38% of the patients were considered impaired at 1 week and 6 weeks postinjury, respectively. Stepwise logistic regression modeling identified admission Galveston Orientation and Amnesia test score, S100B level, and RPQ score at day 3 postinjury to be predictive of poor outcome at 1 week postinjury (c-statistic 0.877); female gender, loss of consciousness, NSE level, and RPQ score at day 3 postinjury were predictive of poor outcome at 6 weeks postinjury (c-statistic 0.895). The discriminative power of the biomarkers alone was limited. CONCLUSIONS: Biomarkers, in conjunction with other readily available determinants of outcome assessed in the acute period after injury, add value in the early prognostication of patients with mTBI. Our findings are consistent with the notion that S100B and NSE point to biological mechanisms underlying poor outcome after mTBI. PMID- 22072009 TI - Aeromobile modular critical care, resuscitation, and surgical suites for operational medicine. PMID- 22072008 TI - A predeployment trauma team training course creates confidence in teamwork and clinical skills: a post-Afghanistan deployment validation study of Canadian Forces healthcare personnel. AB - BACKGROUND: The 10-day Intensive Trauma Team Training Course (ITTTC) was developed by the Canadian Forces (CFs) to teach teamwork and clinical trauma skills to military healthcare personnel before deploying to Afghanistan. This article attempts to validate the impact of the ITTTC by surveying participants postdeployment. METHODS: A survey consisting of Likert-type multiple-choice questions was created and sent to all previous ITTTC participants. The survey asked respondents to rate their confidence in applying teamwork skills and clinical skills learned in the ITTTC. It explored the relevancy of objectives and participants' prior familiarity with the objectives. The impact of different training modalities was also surveyed. RESULTS: The survey showed that on average 84.29% of participants were "confident" or "very confident" in applying teamwork skills to their subsequent clinical experience and 52.10% were "confident" or "very confident" in applying clinical knowledge and skills. On average 43.74% of participants were "familiar" or "very familiar" with the clinical topics before the course, indicating the importance of training these skills. Participants found that clinical shadowing was significantly less valuable in training clinical skills than either animal laboratory experience or experience in human patient simulators; 68.57% respondents thought that ITTTC was "important" or "very important" in their training. CONCLUSIONS: The ITTTC created lasting self reported confidence in CFs healthcare personnel surveyed upon return from Afghanistan. This validates the importance of the course for the training of CFs healthcare personnel and supports the value of team training in other areas of trauma and medicine. PMID- 22072010 TI - Tranexamic acid autoinjector for prehospital care of noncompressible hemorrhage. PMID- 22072011 TI - Highly conductive carbon nanotube buckypapers with improved doping stability via conjugational cross-linking. AB - Carbon nanotube (CNT) sheets or buckypapers have demonstrated promising electrical conductivity and mechanical performance. However, their electrical conductivity is still far below the requirements for engineering applications, such as using as a substitute for copper mesh, which is currently used in composite aircraft structures for lightning strike protection. In this study, different CNT buckypapers were stretched to increase their alignment, and then subjected to conjugational cross-linking via chemical functionalization. The conjugationally cross-linked buckypapers (CCL-BPs) demonstrated higher electrical conductivity of up to 6200 S cm( - 1), which is more than one order increase compared to the pristine buckypapers. The CCL-BPs also showed excellent doping stability in over 300 h in atmosphere and were resistant to degradation at elevated temperatures. The tensile strength of the stretched CCL-BPs reached 220 MPa, which is about three times that of pristine buckypapers. We attribute these property improvements to the effective and stable conjugational cross-links of CNTs, which can simultaneously improve the electrical conductivity, doping stability and mechanical properties. Specifically, the electrical conductivity increase resulted from improving the CNT alignment and inter-tube electron transport capability. The conjugational cross-links provide effective 3D conductive paths to increase the mobility of electrons among individual nanotubes. The stable covalent bonding also enhances the thermal stability and load transfer. The significant electrical and mechanical property improvement renders buckypaper a multifunctional material for various applications, such as conducting composites, battery electrodes, capacitors, etc. PMID- 22072012 TI - Increased secretion of Gas6 by smooth muscle cells in human atherosclerotic carotid plaques. AB - Vitamin K-dependent protein Gas6 (growth-arrest specific gene 6) plays a role in vascular smooth muscle cell (VSMC) survival and migration, as well as in endothelium and leukocyte activation, and could therefore be involved in atherosclerosis. However, the study of mouse models has led to contradictory results regarding the pro- or anti-atherogenic properties of Gas6, and relatively few data are available in human pathophysiology. To better understand the implication of Gas6 in human atherosclerosis, we studied Gas6 expression and secretion in vitro in human VSMC, and analysed the effect of Gas6 on inflammatory gene expression in these cells. We show that Gas6 secretion in VSMC is strongly induced by the anti-inflammatory cytokine transforming growth factor (TGF)beta, and that VSMC stimulation by recombinant Gas6 decreases the expression of inflammatory genes tumour necrosis factor (TNF)alpha and intracellular adhesion molecule (ICAM)-1. The study of Gas6 expression in human carotid endarterectomy samples revealed that Gas6 is mainly expressed by VSMC at all stages of human atherosclerosis, but is not detected in normal vessel wall. Analysis of plaque secretomes showed that Gas6 secretion is markedly higher in non-complicated plaques than in complicated plaques, and that TGFbeta secretion pattern mirrors that of Gas6. We conclude that Gas6 is secreted in human atherosclerotic plaques by VSMC following stimulation by TGFbeta, and that Gas6 secretion decreases with plaque complication. Therefore, we propose that Gas6 acts as a protective factor, in part by reducing the pro-inflammatory phenotype of VSMC. PMID- 22072013 TI - Rituximab abrogates joint destruction in rheumatoid arthritis by inhibiting osteoclastogenesis. AB - OBJECTIVES: To examine how rituximab may result in the inhibition of joint destruction in rheumatoid arthritis (RA) patients. METHODS: Twenty-eight patients with active RA were treated with rituximab. Radiographs of hands and feet before and 1 year after therapy were assessed using the Sharp-van der Heijde score (SHS). Expression of bone destruction markers was evaluated by immunohistochemistry and immunofluorescence of synovial biopsies obtained before and 16 weeks after the initiation of treatment. Serum levels of osteoprotegerin, receptor activator of nuclear factor kappaB ligand (RANKL), osteocalcin and cross linked N-telopeptides of type I collagen (NTx) were measured by ELISA before and 16 weeks post-treatment. RESULTS: After 1 year, the mean (SD) change in total SHS was 1.4 (10.0). Sixteen weeks after treatment there was a decrease of 99% in receptor activator of nuclear factor kappaB-positive osteoclast precursors (p=0.02) and a decrease of 37% (p=0.016) in RANKL expression in the synovium and a trend towards reduced synovial osteoprotegerin expression (25%, p=0.07). In serum, both osteoprotegerin (20%, p=0.001) and RANKL (40%, p<0.0001) levels were significantly reduced 16 weeks after treatment, but the osteoprotegerin/RANKL ratio increased (157%, p=0.006). A trend was found towards an increase of osteocalcin levels (p=0.053), while NTx concentrations did not change. CONCLUSIONS: Rituximab treatment is associated with a decrease in synovial osteoclast precursors and RANKL expression and an increase in the osteoprotegerin/RANKL ratio in serum. These observations may partly explain the protective effect of rituximab on the progression of joint destruction in RA. PMID- 22072014 TI - Incidence of cancer in a nationwide population cohort of 7852 patients with primary Sjogren's syndrome in Taiwan. AB - OBJECTIVES: Patients with primary Sjogren's syndrome (pSS) are at a higher risk of developing non-Hodgkin's lymphoma (NHL). However, little is known with regard to the risk of developing cancers other than NHL. The authors aimed in this study to compare the incidence of cancer in various sites among patients with pSS with the general population of Taiwan. METHODS: The authors used National Health Insurance claims data to establish a nationwide population cohort of 7852 patients with pSS from 2000 to 2008 who did not have cancer prior to diagnosis of pSS. Incidence and standardised incidence ratios (SIRs) for cancer in various sites were calculated. RESULTS: Among patients with pSS, 277 (2.9%) developed cancer. The SIR for cancer was 1.04 (95% CI 0.91 to 1.18) among patients of all ages with pSS and was 2.19 (95% CI 1.43 to 3.21) for patients aged 25-44 years. Female patients with pSS had a higher risk of NHL (SIR 7.1, 95% CI 4.3 to 10.3), multiple myeloma (SIR 6.1, 95% CI 2.0 to 14.2) and thyroid gland cancer (SIR 2.6, 95% CI 1.4 to 4.3) and a lower risk of colon cancer (SIR 0.22, 95% CI 0.05 to 0.65). In contrast, male patients with pSS were not at a higher risk of developing cancer in particular sites. CONCLUSION: Patients with pSS, overall, did not have higher risk of cancer, and only patients aged 25-44 years were at an increased risk of cancer compared with their counterparts in the general population. Cancer screening for patients with pSS, especially female patients, should focus on NHL and multiple myeloma and thyroid gland cancer. PMID- 22072015 TI - A tool to identify recent or present rheumatoid arthritis flare from both patient and physician perspectives: the 'FLARE' instrument. AB - INTRODUCTION: There is a lack of consensus about the definition of flare of rheumatoid arthritis (RA) and a measurement tool. OBJECTIVES: To develop a self administered tool integrating the perspectives of the patient and the rheumatologist, enabling the detection of present or recent-past RA flare. METHODS: The patient perspective was explored by semistructured individual interviews of patients with RA. Two health psychologists conducted a content analysis to extract items best describing flare from the interviews. The physician's perspective was explored through a Delphi exercise conducted among a panel of 13 rheumatologists. A comprehensive list of items produced in the first round was reduced in a four-round Delphi process to select items cited by at least 75% of the respondents. The identified elements were assembled in domains each converted into a statement-to constitute the final self-administered Flare Assessment in Rheumatoid Arthritis (FLARE) questionnaire. RESULTS: The content of 99 patient interviews was analysed, and 10 domains were identified: joint swelling or pain, night pain, fatigue and different emotional consequences, as well as analgesic intake. The Delphi process for physicians identified eight domains related to objective RA symptoms and drug intake, of which only four were common to domains for patients. Finally, 13 domains were retained in the FLARE questionnaire, formulated as 13 statements with a Likert-scale response modality of six answers ranging from 'absolutely true' to 'completely untrue'. CONCLUSION: Two different methods, for patient and physician perspectives, were used to develop the FLARE self-administered questionnaire, which can identify past or present RA flare. PMID- 22072016 TI - Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. AB - OBJECTIVES: To investigate the effect of leptin on cartilage destruction. METHODS: Collagen release was assessed in bovine cartilage explant cultures, while collagenolytic and gelatinolytic activities in culture supernatants were determined by bioassay and gelatin zymography. The expression of matrix metalloproteinases (MMP) was analysed by real-time RT-PCR. Signalling pathway activation was studied by immunoblotting. Leptin levels in cultured osteoarthritic joint infrapatellar fat pad or peri-enthesal deposit supernatants were measured by immunoassay. RESULTS: Leptin, either alone or in synergy with IL 1, significantly induced collagen release from bovine cartilage by upregulating collagenolytic and gelatinolytic activity. In chondrocytes, leptin induced MMP1 and MMP13 expression with a concomitant activation of STAT1, STAT3, STAT5, MAPK (JNK, Erk, p38), Akt and NF-kappaB signalling pathways. Selective inhibitor blockade of PI3K, p38, Erk and Akt pathways significantly reduced MMP1 and MMP13 expression in chondrocytes, and reduced cartilage collagen release induced by leptin or leptin plus IL-1. JNK inhibition had no effect on leptin-induced MMP13 expression or leptin plus IL-1-induced cartilage collagen release. Conditioned media from cultured white adipose tissue (WAT) from osteoarthritis knee joint fat pads contained leptin, induced cartilage collagen release and increased MMP1 and MMP13 expression in chondrocytes; the latter being partly blocked with an anti leptin antibody. CONCLUSIONS: Leptin acts as a pro-inflammatory adipokine with a catabolic role on cartilage metabolism via the upregulation of proteolytic enzymes and acts synergistically with other pro-inflammatory stimuli. This suggests that the infrapatellar fat pad and other WAT in arthritic joints are local producers of leptin, which may contribute to the inflammatory and degenerative processes in cartilage catabolism, providing a mechanistic link between obesity and osteoarthritis. PMID- 22072017 TI - Articular inflammation is controlled by myeloid cell-derived interleukin 1 receptor antagonist during the acute phase of arthritis in mice. AB - OBJECTIVES: To define the cell type (myeloid vs other cells) specific effect of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) deficiency on the acute inflammatory phase of arthritis. METHODS: Arthritis was induced by K/BxN serum transfer in wild-type (WT), IL-1Ra-deficient (IL-1Ra(-/-)) and conditional knockout mice. In the latter, IL-1Ra production was specifically targeted in myeloid cells (IL-1Ra(DeltaM)) or in both hepatocytes and myeloid cells (IL 1Ra(DeltaH+M)). Arthritis severity was clinically evaluated and ankle sections were scored for synovial inflammation and cartilage erosion. Quantitative RT-PCR, western blot and immunohistochemical analyses measured expression, localisation and cellular sources of the different IL-1Ra isoforms in arthritic joints. RESULTS: Total and myeloid cell-specific IL-1Ra deficiency was associated with increased arthritis severity, although disease incidence was similar to that of WT mice. Increased clinical scores were associated with exacerbated synovial inflammation. All IL-1Ra isoforms, except for intracellular (ic)IL-1Ra2, were expressed in arthritic joints of WT mice. In contrast, production of secreted (s)IL-1Ra and icIL-1Ra3 isoforms was markedly decreased in arthritic joints of both IL-1Ra(DeltaM) and IL-1Ra(DeltaH+M) mice. Immunohistochemical and western blot analyses suggested that the icIL-1Ra1 isoform is produced primarily by synovial fibroblasts. CONCLUSION: Myeloid cell-derived IL-1Ra, including both sIL 1Ra and icIL-1Ra3 isoforms, controls articular inflammation during the acute phase of K/BxN serum transfer-induced arthritis. PMID- 22072018 TI - Beginning at the bottom: evidence-based care of diaper dermatitis. AB - Diaper dermatitis (DD), an acute inflammatory reaction of skin in the perineal area, is an extremely common pediatric condition. Nurses' practice of preventing and treating DD is inconsistent and often not evidence-based. In addition, a 2008 Skin Injury Prevalence Study at our hospital revealed that 24% of inpatients had DD. The authors developed a project to determine a consistent and evidence-based approach to DD prevention and treatment including the availability of products. A complete literature review was conducted in addition to benchmarking with other pediatric hospitals, consultation with topic experts, and evaluation of current nursing practice prior to revising the existing perineal skin care nursing standard. The evidence supports frequent diaper changes, use of super absorbent diapers, and protection of perineal skin with a product containing petrolatum and/or zinc oxide. As supported by the literature, we revised the standard to include improvements in practice as well as product updates for prevention and treatment. Hospital-wide implementation of the revised standard included training "Skin Care Champions" to educate staff and support practice improvements. Ongoing education and monitoring by the Skin Care Champions is necessary to further improve the prevention and treatment of DD for our patients. PMID- 22072019 TI - Women's perceptions of centeringpregnancy: a focus group study. AB - OBJECTIVES: CenteringPregnancy, a model of group prenatal care, provides healthcare assessment, education, and support to women. The current study was designed to determine women's perceptions of the CenteringPregnancy program. METHODS: Twenty-one women participating in CenteringPregnancy, as part of a larger study, shared their thoughts related to the strengths and weaknesses of their healthcare, thoughts on improvement, and how the care impacted their health and health behaviors. A thematic and iterative analysis process, assisted by Ethnograph 6.0, allowed for the emersion of important themes that were validated in a member check process. RESULTS: The focus group participants provided rich insights into their prenatal experiences in CenteringPregnancy. Four substantive themes emerged from the data: It's about respect, Knowledge is Power, I'm a better mother, and Supporting each other. CONCLUSIONS: CenteringPregnancy was well-received by urban, low-income women during their pregnancy and may have value with select populations. Themes, exemplar quotes, and participant observations may assist others interested in implementing the CenteringPregnancy model of care. PMID- 22072020 TI - Time-dependency, predictors and clinical impact of infarct transmurality assessed by magnetic resonance imaging in patients with ST-elevation myocardial infarction reperfused by primary coronary percutaneous intervention. AB - Previous studies analyzing the relation between time-to-reperfusion, infarct size, microvascular obstruction (MO) and infarct transmurality in patients with ST-elevation myocardial infarction (STEMI) reperfused by primary percutaneous coronary intervention (PCI) reported inconsistent results. Furthermore, it remains unclear, if transmural infarction is associated with adverse clinical outcome. The present study included STEMI patients reperfused by primary PCI (n = 322) within 720 min after symptom-onset undergoing contrast-enhanced magnetic resonance imaging (CMR) at a median of 3 days after the index event [interquartile range (IQR) 2-4]. Patients were subcategorized into tertiles according to time-to-reperfusion. Infarct size and MO were assessed approximately 15 min after gadolinium-injection. Infarct transmurality was assessed by a score with late-enhancement grading as <25, 25-50, 51-75 and >75% transmurality analyzing all 17 left ventricular segments. Clinical follow-up was performed after 20 months (IQR 13;29). The primary endpoint was defined as a composite of death and congestive heart failure. The median time-to-reperfusion was 230 min (IQR 153;390). Infarct size and MO did not increase significantly with longer time-to-reperfusion (p = 0.16 and p = 0.44, respectively). In contrast to infarct size and MO, the infarct transmurality score progressed significantly with increasing ischemic time (p < 0.001). In multivariable logistic regression analysis, time-to-reperfusion was identified as an independent predictor for transmural infarction (p = 0.03). However, transmural infarction was not predictive of the primary composite clinical endpoint (p = 0.22). In conclusion, in STEMI patients reperfused by primary PCI, time-to-reperfusion was an independent predictor for transmural infarction but not for infarct size and MO. However, transmural infarction was not predictive of death and congestive heart failure. PMID- 22072021 TI - Completion of and early response to chemoradiation among human immunodeficiency virus (HIV)-positive and HIV-negative patients with locally advanced cervical carcinoma in South Africa. AB - BACKGROUND: Very few published studies have dealt with the management of locally advanced cervix carcinoma among human immunodeficiency virus (HIV)-positive patients. The objective of this study was to compare the clinical characteristics, radiation and chemotherapy treatments, and outcomes in a cohort of HIV-positive and HIV-negative women with cervical cancer. METHODS: The authors reviewed the charts of 59 HIV-positive patients and 324 HIV-negative patients who had stage IB1 to IIIB cervical carcinoma and who received radiation therapy. Demographic and clinical characteristics were compared at the time of diagnosis; and radiation doses, chemotherapy cycles, and responses were compared at the time of brachytherapy and at 6-week follow-up. Logistic regression models of response to treatment were developed. RESULTS: Forty-nine HIV-positive patients (88.1%) but only 213 HIV-negative patients (65.7%) presented with stage IIIB disease (P = .009). Forty-seven HIV-positive patients (79.7%) and 291 HIV-negative patients (89.8%) completed the equivalent dose of 68 Grays (Gy) external-beam radiation and high-dose-rate brachytherapy. (P = .03). Of the 333 patients who commenced concurrent chemotherapy, 26 HIV-positive patients (53.1%) and 212 HIV-negative patients (74.6%) completed >=4 weekly cycles of platinum-based treatment. Follow up was censured at 6 weeks. In models that included age, disease stage, HIV status, and treatment, a poor response at 6 weeks was associated only with stage IIIB disease (odds ratio, 2.39; 95% confidence interval, 1.45-3.96) and receiving an equivalent radiation dose in 2-Gy fractions of <68 Gy (OR, 3.14; 95% CI, 1.24 7.94). CONCLUSIONS: HIV-positive patients fared worse than HIV-negative patients because of later presentation and a decreased likelihood of completing treatment. The current findings emphasize the importance of completing irradiation therapy. Further studies will address the association of these variables with survival. PMID- 22072022 TI - Coexisting systemic lupus erythematosus and ankylosing spondylitis: a case report and review of the literature. PMID- 22072023 TI - Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus. AB - BACKGROUND: Even mild renal impairment is associated with increased atherosclerosis and cardiovascular mortality. Cystatin C, a novel measure of renal function, is more sensitive than conventional creatinine-based measures for the detection of subtle renal impairment. Increased cystatin concentrations are also associated with cardiovascular risk, independently of conventional measures of renal function. This study examined the hypothesis that cystatin C is elevated in systemic lupus erythematosus (SLE) and is associated with coronary atherosclerosis. METHODS: Serum cystatin C, creatinine, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, coronary artery calcium score (CACS), Framingham risk score (FRS), Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD-eGFR), and other clinical parameters were measured in 118 patients with SLE and 83 control subjects. The independent association between concentrations of cystatin C and SLE was evaluated using multivariable linear regression models, and the relationship between renal measures and coronary calcium was assessed with multivariable proportional odds logistic regression models. RESULTS: Cystatin C, but not other measures of renal function, was significantly higher in patients with SLE than in controls (1.09 [interquartile range, IQR: 0.85-1.28] mg/l vs. 0.89 [IQR: 0.76-0.99] mg/l; p < 0.001 after adjustment for age, race, sex and MDRD-eGFR). Cystatin C was significantly associated with SLICC (p = 0.04), erythrocyte sedimentation rate (ESR) (p = 0.02), TNF-alpha (p = 0.008) and IL-6 (p = 0.01) after adjustment for age, race, and sex. Cystatin C was not significantly correlated with coronary calcium score in SLE (rho=0.096, p = 0.31) and the association remained non-significant after adjustment for age, race, sex, and Framingham risk score (p = 0.99). CONCLUSIONS: Cystatin C was higher in patients with SLE than in control subjects even after adjustment for conventional measures of renal function. Cystatin C was significantly correlated with several markers of inflammation in SLE but was not associated with coronary atherosclerosis. Subtle renal dysfunction does not appear to be directly associated with accelerated atherosclerosis in SLE. PMID- 22072024 TI - Current state of evidence on 'off-label' therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland--a consensus report. AB - Systemic lupus erythematosus (SLE) can be a severe and potentially life threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence. PMID- 22072025 TI - Decreased serum levels of TGF-beta1 are associated with renal damage in female patients with systemic lupus erythematosus. AB - INTRODUCTION: Transforming growth factor beta1 (TGF-beta1) has a large role in the control of autoimmunity. TGF-beta1 production by lymphocytes is reduced in systemic lupus erythematosus (SLE). Decreased levels of TGF-beta1 might associate to disease susceptibility, activity and organ damage in SLE. However, the correlation between TGF-beta1 levels and severity of renal damage in SLE has not been examined. METHODS: The present study was undertaken to assess the serum levels of total and active TGF-beta1 in 150 female patients with SLE and 31 healthy women. Simple and multiple regression analyses between TGF-beta1 levels and the diseases-related variables were performed in patients with SLE. RESULTS: Serum levels of both total and active TGF-beta1 were significantly reduced in patients with SLE compared with levels in healthy controls (p < 0.01). Total TGF beta1 levels correlated positively with white blood cell, platelet counts, calculated glomerular filtration rate (GFR), and active TGF-beta1 level, and inversely with erythrocyte sedimentation rate (ESR). In multiple regression analysis, ESR and platelet counts remained determinants of total TGF-beta1. Total TGF-beta1 levels were lower in patients with high disease activity (SLEDAI > 10) and severe organ damage (SLICC > 3). Significantly lower levels of total TGF beta1 were found in patients with severe renal damage, i.e. lower TGF-beta1 in patients with 24-h urine protein over 3.5 g than in those with below 3.5 g (p < 0.05); lower TGF-beta1 in patients with GFR less than 50 ml/min than in those with over 50 ml/min (p < 0.05). In contrast, active TGF-beta1 only correlated with platelet counts. There was no association between renal damage and the levels of active TGF-beta1. CONCLUSION: This study demonstrates significantly reduced serum levels of both total and active TGF-beta1 in women with SLE compared with healthy women. Total TGF-beta1 levels are correlated negatively with ESR and positively with blood platelets. Total TGF-beta1 levels were lower in SLE patients with high disease activity and severe organ damage. Importantly, the severity of the renal damage was associated with decreased serum levels of total TGF-beta1, suggesting that TGF-beta1 might be involved in pathogenesis of renal damage caused by lupus nephritis. PMID- 22072026 TI - BPH: perioperative advantages of laser treatment. PMID- 22072027 TI - Prostate cancer: who will win the CRPC drug race? PMID- 22072032 TI - Tyrosine nitration affects thymidylate synthase properties. AB - Highly purified preparations of thymidylate synthase, isolated from calf thymus, and L1210 parental and FdUrd-resistant cells, were found to be nitrated, as indicated by a specific reaction with anti-nitro-tyrosine antibodies, suggesting this modification to appear endogenously in normal and tumor tissues. Each human, mouse and Ceanorhabditis elegans recombinant TS preparation, incubated in vitro in the presence of NaHCO(3), NaNO(2) and H(2)O(2) at pH 7.5, underwent tyrosine nitration, leading to a V(max)(app) 2-fold lower following nitration of 1 (with human or C. elegans TS) or 2 (with mouse TS) tyrosine residues per monomer. Enzyme interactions with dUMP, meTHF or 5-fluoro-dUMP were not distinctly influenced. Nitration under the same conditions of model tripeptides of a general formula H(2)N-Gly-X-Gly-COOH (X = Phe, Tyr, Trp, Lys, Arg, His, Ser, Thr, Cys, Gly), monitored by NMR spectroscopy, showed formation of nitro-species only for H Gly-Tyr-Gly-OH and H-Gly-Phe-Gly-OH peptides, the chemical shifts for nitrated H Gly-Tyr-Gly-OH peptide being in a very good agreement with the strongest peak found in (15)N-(1)H HMBC spectrum of nitrated protein. MS analysis of nitrated human and C. elegans proteins revealed several thymidylate synthase-derived peptides containing nitro-tyrosine (at positions 33, 65, 135, 213, 230, 258 and 301 in the human enzyme) and oxidized cysteine (human protein Cys(210), with catalytically critical Cys(195) remaining apparently unmodified) residues. PMID- 22072033 TI - How to introduce virtual microscopy (VM) in routine diagnostic pathology: constraints, ideas, and solutions. AB - CONTEXT: Virtual microscopy which is the diagnostic work with digitized microscopic images in tissue - based diagnosis is in its childhood in being implemented in routine diagnosis. Until today, only a few pathology institutions take use of this new technology, although it is available since several years. Why? DESIGN: Virtual microscopy requires a new workflow organisation in the pathologist's diagnostic procedure. At a first view, the laboratory workflow seems to remain untouched to a high degree. However, the used laboratory information system (LIS), which is commonly built in a hierarchic order, has to be adjusted at its highest levels, i.e., diagnosis statement, quality evaluation, submission to the clinician (hospital information system), and feedback to the laboratory. Therefore, the laboratory's workflow is involved at all levels too, and the LIS has to be changed or adjusted to the requirements of VM. VM systems are usually equipped with a viewer that mimics the viewing of a conventional microscope, and do not offer access to sensitive nodes of the LIS. Similar, LIS are usually closed and fixed systems because of data security and certification demands. Thus, VM systems have to possess communication access at different LIS levels together with steering commands for the LIS in close association with the diagnostic quality and efficiency (for example demands for additional stains, immunohistochemical or quantitative image methods, etc.), as well as expert consultation, or panel discussion. OUTCOME: An implementation of an open and active LIS - VM management system could significantly promote the introduction of VM into routine diagnostic surgical pathology. The management system has to coordinate and translate the demands of VM to LIS (and vice versa), and to assure the communication with HIS. Mandatory features include streaming of the laboratory workflow, feedback commands to LIS, as well as regulation of temporary priority levels. CONCLUSION: A successful implementation of VM systems in routine tissue-based diagnosis requires communicative management systems as long as VM is considered to be a "stand alone system" that just mimics a conventional microscope. PMID- 22072034 TI - Injury Free Coalition Annual Supplement: editor's foreword. PMID- 22072035 TI - Welcome to the proceedings of the 2010 Annual Meeting of the Injury Free Coalition for Kids. PMID- 22072036 TI - On the road with injury prevention--an analysis of the efficacy of a mobile injury prevention exhibit. AB - BACKGROUND: To assess the effectiveness of a mobile injury prevention vehicle (mobile safety street [MSS]) with a hands-on curriculum on instruction and retention of safety knowledge compared with traditional classroom safety curriculum among grade 5 elementary school children. METHODS: Grade 5 students (n = 1,692) were asked to participate in the study as either the intervention group (MSS experience) or the comparison group (traditional classroom safety curriculum). Each student in the intervention group was asked to complete a series of three surveys. The first survey was given before the MSS visit (Fall 2009), the second immediately following the MSS visit (Fall 2009), and a third given 6 months after the MSS visit (Spring 2010) to measure knowledge retention. Students in the comparison group were asked to complete two surveys. The first survey was given at the same time as the intervention group (Fall 2009) and the second was given after the completion of the traditional classroom safety curriculum (Spring 2010). RESULTS: Students scored on average 5.67 of 10 (5.56 5.80) before any safety instruction was given. After MSS instruction, mean scores showed a significant increase to 7.43 of 10 (7.16-7.71). Such increase was still measurable 6 months after the intervention 7.34 (7.04-7.66). The comparison group saw a significant increase in their mean scores 6.48 (6.10-6.89), but the increase was much smaller than the intervention group. CONCLUSIONS: Community based injury prevention programs are essential to reducing preventable injury and deaths from trauma. This study demonstrates that a hands-on program is more effective than traditional methods for providing safety knowledge. PMID- 22072037 TI - Targeting pediatric pedestrian injury prevention efforts: teasing the information through spatial analysis. AB - BACKGROUND: Pediatric pedestrian injuries remain a major cause of childhood death, hospitalization, and disability. To target injury prevention efforts, it is imperative to identify those children at risk. Racial disparities have been noted in the rates of pediatric pedestrian injury and death. Children from low income families living in dense, urban residential neighborhoods have a higher risk of sustaining pedestrian injury. Geographic information systems (GIS) analysis of associated community factors such as child population density and median income may offer insights into prevention. METHODS: Using trauma registry E-codes for pedestrian motor vehicle crashes, children younger than 16 years were identified, who received acute care and were hospitalized at the University of Chicago Medical Center, a Level I pediatric trauma center, after being struck by a motor vehicle from 2002 to 2009. By retrospective chart review and review of the Emergency Medical Services run sheets, demographic data and details of the crash site were collected. Crash sites were aggregated on a block by block basis. A "hot spot" analysis was performed to localize clusters of injury events. Using Gi* statistical method, spatial clusters were identified at different confidence intervals using a fixed distance band of 400 m (~ 1/4 mile). Maps were generated using GIS with 2000 census data to evaluate race, employment, income, density of public and private schools, and density of children living in the neighborhoods surrounding our medical center where crash sites were identified. Spatial correlation is used to identify statistically significant locations. RESULTS: There were 3,521 children admitted to the University of Chicago Medical Center for traumatic injuries from 2002 to 2009; 27.7% (974) of these children sustained injuries in pedestrian motor vehicle injuries. From 2002 to 2009, there were a total of 106 traumatic deaths, of which 29 (27.4%) were due to pedestrian motor vehicle crashes. Pediatric pedestrian motor vehicle crash sites occurred predominantly within low-income, predominantly African-American neighborhoods. A lower prevalence of crash sites was observed in the predominantly higher income, non-African-American neighborhoods. CONCLUSIONS: Spatial analysis using GIS identified associations between pediatric pedestrian motor vehicle crash sites and the neighborhoods served by our pediatric trauma center. Pediatric pedestrian motor vehicle crash sites occurred predominantly within low-income, African American neighborhoods. The disparity in prevalence of crash sites is somewhat attributable to the lower density of children living in the predominantly higher income, non-African-American neighborhoods, including the community immediately around our hospital. Traffic volume patterns, as a denominator of these injury events, remain to be studied. PMID- 22072038 TI - Restraint use law enforcement intervention in Latino communities. AB - BACKGROUND: Motor vehicle crashes are the leading cause of death for U.S. Latinos aged 1 to 35 years. Restraint use is an effective means of prevention of motor vehicle crash injury. Effective interventions to raise restraint use include the following: legislation, law enforcement, education, and equipment distribution. The effects of law enforcement interventions in Latino immigrant communities are understudied. We measured the community-level effect of a combined intervention that included warnings and citations phase enforcement in Latino communities. METHODS: We designed and implemented in two of three Latino-majority communities a multicomponent intervention consisting of a community awareness campaign, restraint use education with equipment distribution, and a two-staged law enforcement intervention. Restraint use observations were conducted in all three communities at baseline, after the warnings phase and again after the citations phase of the intervention were completed. RESULTS: The combined intervention of community awareness, education, child passenger restraint distribution, and law enforcement focused on educational traffic stops with incentives and warnings was associated with a significant increase in both driver and child passenger restraint use in one intervention community, but only driver restraint increased to a level of significance in the other intervention community; significant increase was also noted among nonintervention drivers. The citations phase of the intervention did not result in a significant increase in restraint use and was complicated by interruptions due to unlicensed drivers. CONCLUSION: The combined effort of community awareness, education, equipment distribution and law enforcement intervention that included incentives and warnings may be effective at increasing seat belt use in Latino communities without the need for citations. PMID- 22072039 TI - Under the influence with a child in the car: implications for child safety and caregiver intervention. AB - BACKGROUND: Injury is the leading cause of death for those aged 1 year to 44 years in the United States, with motor vehicle collisions (MVCs) the leading cause of injury-related deaths. Little data exist on the relationship between caregiver alcohol and drug use at the time of MVC and child passenger outcomes. We examined the relationship between caregiver substance use in MVCs and a number of demographic, crash severity, and medical outcomes for caregivers and children. METHODS: We identified family groups treated in the emergency department of a regional Level II trauma center after an MVC in a 1-year period from July 1, 2005, to June 30, 2006. The distribution and means of characteristics for substance and nonsubstance users were compared using chi analysis and Student's t tests, respectively. RESULTS: One in 10 vehicles contained an intoxicated caregiver at the time of MVC. In 363 identified caregivers, intoxication was associated with being male (p < 0.001), lack of safety device use (p = 0.003), rollover (p = 0.008), and ejection (p = 0.016). In the 278 family groups, intoxicated caregivers were related to child ejection (p = 0.009), the need for child hospital admission (p < 0.001), and driver intoxication was related to child lack of restraint (p = 0.045). CONCLUSION: These findings suggest a substantial number of child MVC victims arrive at the emergency room after riding with an intoxicated caregiver. Findings support the need for prevention programs focusing on substance use and driving for male caregivers, and further investigation on the need for screening and intervention for caregivers' risky alcohol and drug use after a child's MVC. PMID- 22072040 TI - Impact of Connecticut's graduated driver licensing system on teenage motor vehicle crash rates. AB - BACKGROUND: In response to high rates of teen motor vehicle crashes (MVCs) many states have enacted graduated driver licensing (GDL) systems. GDL delays full licensure and allows beginners to obtain experience under lower risk conditions. The purpose of this study is to evaluate the impact over the past 10 years to determine its effect on teen MVCs. METHODS: Connecticut MVC data from 1999 to 2008 were analyzed. Percent change (1999 vs. 2008) in MVC rates per 10,000 registered drivers was calculated by age, gender, during the night restriction (11:00 pm and 5:00 am), and MVCs with passengers. Linear regression analysis estimated the decrease of MVC rates each year. RESULTS: The MVC rate decreased by 40% for 16-year-old and 30% for 17-year-old drivers. In comparison, rates among 18-year-old, 19-year-old, 25- to 29-year-old, and 30- to 59-year-old drivers were reduced by 16%, 7%, 8%, and 11%, respectively. The MVC rate for 20- to 24-year old drivers increased by 1%. During nighttime restricted driving times, MVC rates decreased by 54% among 16-year-old and 49% among 17-year-old drivers. The MVC rate with passengers decreased by 65% for 16-year-old and 53% for 17-year-old drivers. In comparison, rates of nighttime and with passenger MVCs among older drivers were significantly less. CONCLUSIONS: Implementation of Connecticut's GDL system has resulted in significant reductions in MVC rates among novice drivers. This analysis provides a method for other states to examine the impact of their GDL system. PMID- 22072041 TI - "Non-bite dog-related" injuries: an overlooked injury mechanism in the pediatric population. AB - BACKGROUND: Each year, approximately 4.7 million Americans sustain dog bites, the majority of which occur in children. In response to this alarming trend, injury prevention programs across the country have focused efforts on preventing dog bites in children. However, little attention has been given to non-bite dog related injuries, and to date, no data have been presented on this type of injury in the western literature. METHODS: After Institutional Review Board approval (IRB No. 07100185) was obtained, data from the trauma registry for all children (ages, 0-20 years) admitted to our Level I pediatric trauma center were evaluated from 2001 to 2007. Information regarding dog-related injuries was obtained. Data were divided into injuries related to bites and non-bites. Demographics, injury pattern, and outcome were evaluated. Descriptive statistics, Student's t test, and Fisher's exact/chi analyses were preformed. RESULTS: Over the 6-year period reviewed, 191 (2%) children were admitted to the Benedum Trauma Program for dog related injuries. Thirty-four (18%) children sustained non-bite-related injuries while the remainder sustained bite/scratch injuries. Twenty-six (76%) of the children sustained injuries directly due to contact with dogs; four (12%) of them were injured after falling while being carried by adults who either tripped over a dog or were pushed by a dog. The remaining four (12%) children sustained injuries while colliding with dogs while on motorized and/or nonmotorized vehicles. Abrasions/lacerations and head injury occurred most frequently, followed by extremity fractures, particularly of the femur. Children injured by non-bite-related mechanisms were more severely injured than those sustained a bite, although the Injury Severity Score in both groups was low. CONCLUSION: Dog bites have been recognized around the world as a substantial public health problem particularly in children. In our experience, we have seen that non-bite related injuries should not be ignored. The injuries seen in this subset of children are the result of being struck or pushed, resulting in multiple, potentially severe injuries. These data underscore the unpredictable nature of animals and the need for adult supervision when animals and children interact. PMID- 22072042 TI - Behaviors of young children around microwave ovens. AB - BACKGROUND: Scald burn injuries are the leading cause of burn-related emergency room visits and hospitalizations for young children. A portion of these injuries occur when children are removing items from microwave ovens. This study assessed the ability of typically developing children aged 15 months to 5 years to operate, open, and remove the contents from a microwave oven. METHODS: The Denver Developmental Screening Test II was administered to confirm typical development of the 40 subjects recruited. All children recruited and enrolled in this study showed no developmental delays in any domain in the Denver Developmental Screening Test II. Children were observed for the ability to open both a push and pull microwave oven door, to start the microwave oven, and to remove a cup from the microwave oven. RESULTS: All children aged 4 years were able to open the microwaves, turn on the microwave, and remove the contents. Of the children aged 3 years, 87.5% were able to perform all study tasks. For children aged 2 years, 90% were able to open both microwaves, turn on the microwave, and remove the contents. In this study, children as young as 17 months could start a microwave oven, open the door, and remove the contents putting them at significant risk for scald burn injury. CONCLUSIONS: Prevention efforts to improve supervision and caregiver education have not lead to a significant reduction in scald injuries in young children. A redesign of microwave ovens might prevent young children from being able to open them thereby reducing risk of scald injury by this mechanism. PMID- 22072043 TI - Goods for Guns--the use of a gun buyback as an injury prevention/community education tool. AB - BACKGROUND: US children aged between 5 years and 14 years have a rate of gun related homicide 17 times higher and a rate of gun-related suicide and unintentional firearm injury 10 times higher than other developed countries. Gun buyback programs have been criticized as ineffective interventions in decreasing violence. The Injury Free Coalition for Kids-Worcester (IFCK-W) Goods for Guns buyback is a multipronged approach to address these concerns and to reduce the number of firearms in the community. METHODS: The IFCK-W buyback program is funded by corporate sponsors, grants, and individual donations. Citizens are instructed to transport guns, ammunition, and weapons safely to police headquarters on two Saturdays in December. Participants are guaranteed anonymity by the District Attorney's office and receive gift certificates for operable guns. Trained volunteers administer an anonymous survey to willing participants. Individuals who disclose having unsafely stored guns remaining at home receive educational counseling and trigger locks. Guns and ammunition are destroyed at a later time in a gun crushing ceremony. RESULTS: Since 2002, 1,861 guns (444 rifle/shotgun, 738 pistol/revolver, and 679 automatic/semiautomatic) have been collected at a cost of $99,250 (average, $53/gun). Seven hundred ten people have surrendered firearms, 534 surveys have been administered, and ~ 75 trigger locks have been distributed per year. CONCLUSIONS: IFCK-W Goods for Guns is a relatively inexpensive injury prevention model program that removes unwanted firearms from homes, raises community awareness about gun safety, and provides high-risk individuals with trigger locks and educational counseling. PMID- 22072044 TI - Epidemiology of bone fracture across the age span in blacks and whites. AB - BACKGROUND: Gender and racial disparities in injury mortality have been well established, but less is known regarding differences in fracture-related hospitalizations across the age span. METHODS: Cross-sectional analysis of annual incident fracture hospital admissions used statewide acute care hospital discharge data (Statewide Program and Research Cooperative System) for non Hispanic White (n = 138,763) and non-Hispanic Black (n = 19,588) residents of New York State between 2000 and 2002. US census data with intercensal estimates were used to ascertain the population at risk. Gender- and race-specific incident fracture was calculated in 5-year age intervals. The chi test was used to analyze categorical variables. RESULTS: Mechanisms of injury vary by race and gender in their relative contribution to injury-related fractures across the age span. Black males exhibited higher fracture incidence until approximately age 62, while incidence in women diverged around age 45. Total motor vehicle traffic-related fracture hospitalization is bimodal in Whites but not in Blacks. Over the life span, all groups exhibited bimodal pedestrian fractures with pedestrian fractures accounting for 8.8% and 2.5% of all fractures in Blacks and Whites, respectively. Racial disparities were present from preschool through age 70. Violence-related fractures were 10 times higher in Blacks, accounting for 18.2% of hospitalizations. Black males exhibit higher fracture incidence due to violence by age 5 and higher gun violence by age 10; both remain elevated through age 75. CONCLUSIONS: Despite historical studies demonstrating higher bone density in Blacks, this study found racial disparities with increased fracture risk in both Black children and adults across most nonfall-related injury mechanisms examined. PMID- 22072045 TI - The pediatric hospital incident command system: an innovative approach to hospital emergency management. PMID- 22072046 TI - Comparative study of polysaccharides from reproductive and sterile tissues of five brown seaweeds. AB - Sterile and reproductive tissues of five brown algae (Sargassum pallidum, Silvetia babingtonii, Fucus evanescens, Saccharina japonica, and Alaria ochotensis) from Russian Far East seas were compared for the content and monosaccharide composition of fucoidans as well as the content of laminarans and alginic acids. It was proved that reproduction has an apparent effect on fucoidan content and its monosaccharide composition. Fucoidan content in fertile tissues was shown to be 1.3-1.5 times as high as in sterile ones. Based on the present and previously reported data, we believe that fucoidan accumulation during the development of reproductive structure is a general trend for brown seaweeds. Reproduction also caused changes in the monosaccharide composition. As a result, fertile plants synthesized fucoidan with less heterogeneous monosaccharide composition in comparison with sterile ones. Structural changes of this polysaccharide are species-specific and perhaps depend on the type of the synthesized polysaccharide. The fertile plants of S. babingtonii yielded the highest fucoidan content [25% dry weight (dw)] among the tested species, whereas the maximum alginic acid content was found for the sterile tissues of S. japonica up to 43% dw. There was no general trend in alginic acid content variation during sporulation. The alginic acid content was much higher in the sterile tissues of S. japonica in comparison with the fertile ones. On the contrary, the fertile tissues of A. ochotensis contained more alginic acid than the sterile ones. PMID- 22072047 TI - Molecular characterization of a nonfibrillar collagen from the marine sponge Chondrosia reniformis Nardo 1847 and positive effects of soluble silicates on its expression. AB - We report here the complete cDNA sequence of a nonfibrillar collagen (COLch) isolated from the marine sponge Chondrosia reniformis, Nardo 1847 using a PCR approach. COLch cDNA consists of 2,563 nucleotides and includes a 5' untranslated region (UTR) of 136 nucleotides, a 3' UTR of 198 nucleotides, and an open reading frame encoding for a protein of 743 amino acids with an estimated M (r) of 72.12 kDa. The phylogenetic analysis on the deduced amino acid sequence of C-terminal end shows that the isolated sequence belongs to the short-chain spongin-like collagen subfamily, a nonfibrillar group of invertebrate collagens similar to type IV collagen. In situ hybridization analysis shows higher expression of COLch mRNA in the cortical part than in the inner part of the sponge. Therefore, COLch seems to be involved in the formation of C. reniformis ectosome, where it could play a key role in the attachment to the rocky substrata and in the selective sediment incorporation typical of these organisms. qPCR analysis of COLch mRNA level, performed on C. reniformis tissue culture models (fragmorphs), also demonstrates that this matrix protein is directly involved in sponge healing processes and that soluble silicates positively regulate its expression. These findings confirm the essential role of silicon in the fibrogenesis process also in lower invertebrates, and they should give a tool for a sustainable production of marine collagen in sponge mariculture. PMID- 22072048 TI - Preliminary development of a lymphedema symptom assessment scale for patients with head and neck cancer. AB - PURPOSE: Currently, no instruments are available to assess symptoms secondary to lymphedema in patients with head and neck cancer (HNC). The study aim was to develop and conduct preliminary tests of such an instrument. METHODS: A preliminary item pool was generated from a literature review, previous work in breast cancer-related lymphedema, and an observational study. The item pool was revised based on an expert panel's suggestions and feedback from 18 patients with HNC. The current questionnaire, the Lymphedema Symptom Intensity and Distress Survey-Head and Neck (LSIDS-H&N), was then pilot tested in 30 patients with HNC. RESULTS: Preliminary testing (1) demonstrated feasibility, readability, and ease of use of the LSIDS-H&N and (2) identified that there was a considerable level of symptom burden in the cohort of patients in the piloting sample. CONCLUSION: Content validity of the LSIDS-H&N was supported by the expert panel during development of the LSIDS-H&N. Further testing is ongoing. PMID- 22072049 TI - What are the perceived needs and challenges of informal caregivers in home cancer palliative care? Qualitative data to construct a feasible psycho-educational intervention. AB - PURPOSE: Tailored and specific interventions for informal caregivers in palliative care are rare. We aimed to generate evidence to inform a subsequent appropriate intervention based on caregivers' experiences. METHOD: Single, semi structured qualitative interviews were undertaken with 20 informal cancer caregivers of home cancer palliative care. RESULTS: Carers reported the need to be prepared for their caring role, to be visible to professionals, to receive clear and specific information about the patient's condition, and to be emotionally supported. They described challenges as uncertainty, distress at witnessing disease progression and the daily struggle with financial issues, personal time, own health and sleep problems. CONCLUSIONS: Considering the time pressures and restricted caregiver time, the intervention should be brief and should aim to enhance their visibility as service recipients, patient-specific information giving, preparation for their role, and emotional support. PMID- 22072050 TI - Thyroid cancer patients' involvement in adjuvant radioactive iodine treatment decision-making and decision regret: an exploratory study. AB - PURPOSE: We explored regret in thyroid cancer patients, relating to the decision to accept or reject adjuvant radioactive iodine treatment. METHODS: We studied patients with a recent diagnosis of early stage papillary thyroid carcinoma, in whom treatment decisions on adjuvant radioactive iodine had been finalized. Participants completed a Decision Regret Scale questionnaire. We asked the participants to identify who made the final decision about radioactive iodine treatment. We explored the relationship between decision regret and a) degree of patient involvement in decision-making and b) receipt of radioactive iodine treatment. RESULTS: We included 44 individuals, more than half of whom received adjuvant radioactive iodine treatment (26/44). Decision regret was generally low (mean 22.1, standard deviation [SD] 13.0). Participants reported that the final treatment decision was made by the following: patient and doctor (52.3%, 23/44), completely the patient (27.3%, 12/44), or completely the physician (20.5%, 9/44). Decision regret significantly differed according to who made the final decision: the patient (mean 19.0, SD 11.3), patient and doctor (mean 19.5, SD 7.4), and the doctor (mean 32.9, SD 20.37) (F = 4.569; degrees of freedom = 2, 41; p = 0.016). There was no significant difference in decision regret between patients who received radioactive iodine and those who did not (mean difference -2.5; 95% confidence interval -10.6, 5.6; p = 0.540). CONCLUSION: Thyroid cancer patients who reported being involved in the final treatment decision on adjuvant radioactive iodine had less regret than those who did not. PMID- 22072051 TI - A novel approach to paraneoplastic intestinal pseudo-obstruction. AB - Paraneoplastic neurologic syndromes (PNS) are uncommon, affecting fewer than 1 in 10,000 patients with cancer. PNS, while rare, can cause significant morbidity and impose enormous socio-economic costs, besides severely affecting quality of life. PNS can involve any part of the nervous system and can present as limbic encephalitis, subacute cerebellar ataxias, opsoclonus-myoclonus, retinopathies, chronic intestinal pseudo-obstruction (CIPO), sensory neuronopathy, Lambert-Eaton myasthenic syndrome, stiff-person syndrome, and encephalomyelitis. The standard of care for CIPO includes the use of promotility and anti-secretory agents and the resection of the non-functioning gut segment; all of which can cause significant compromise in the quality of life. There is significant evidence that paraneoplastic neurologic syndromes are associated with antibodies directed against certain nerve antigens. We successfully treated a patient with CIPO in the setting of small cell lung cancer with a combination of rituximab and cyclophosphamide. The patient, who had failed to respond to prokinetic agents, anti-secretory therapy, and multiple resections, responded to the immunomodulatory therapy, with minimal residuals with PEG tube feeding and sustained ostomy output. The use of rituximab and cyclophosphamide should therefore be considered in patients with CIPO, especially if it can avoid complicated surgical procedures. PMID- 22072052 TI - Sterically stabilized liposomes incorporating the novel anticancer agent phospho ibuprofen (MDC-917): preparation, characterization, and in vitro/in vivo evaluation. AB - PURPOSE: To incorporate phospho-ibuprofen (P-I), a lipophilic, water insoluble novel anti-cancer agent, into pegylated liposomes and upon formulation optimization to evaluate its antitumor activity in vitro and in vivo. METHODS: P I loaded liposomes were prepared using the thin-film hydration method, and characterized for size, zeta potential, drug content and drug release. We examined their physical stability by particle size changes; their lyophilization ability in the presence of cryoprotectants; and their antitumor activity in vitro in human cancer cell lines and in vivo in a xenograft murine model. RESULTS: P-I was successfully loaded into liposomes consisting of soy-PC and PEG(2000)-PE. These liposomes were <150 nm in diameter; exhibited prolonged stability in suspension and can be lyophilized using sucrose as cryoprotectant. P-I liposomes inhibited the growth of human cancer cell lines in vitro and in vivo of xenograft in nude mice to a greater extent than free P-I. CONCLUSIONS: High levels of P-I can be incorporated into liposomes which can be lyophilized in the presence of sucrose and showed good stability upon storage. Moreover, these drug incorporating liposomes were capable of inhibiting the growth of xenografted tumors in mice more effectively than free P-I. These results justify further development of the P-I liposomes. PMID- 22072054 TI - Haplotypes and haplotype-pairs of IL-1 beta and IL-6 genes and risk of non fatal myocardial infarction in the Western New York Acute MI Study. PMID- 22072053 TI - Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine. AB - PURPOSE: To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(epsilon-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine. METHODS: Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity. RESULTS: Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL. CONCLUSIONS: These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides. PMID- 22072055 TI - Menstrual migraine: update on pathophysiology and approach to therapy and management. AB - OPINION STATEMENT: Menstrual migraine (MM) is often reported to be more severe and more resistant to treatment than other migraines. Nevertheless, initial treatment should be the same as for any migraine. When results of acute therapy are incomplete or unsatisfactory, preventive strategies are warranted, including both pharmacologic preventives and careful adherence to lifestyle modifications. Where MM differs from other attacks is in its predictable timing and discrete precipitants. These differences allow for unique preventive strategies that target either the timing of the attacks or their hormonal precipitants. Nonspecific MM strategies-those that do not address the hormonal mechanism include scheduled dosing of nonsteroidal anti-inflammatory drugs (NSAIDs) or triptans throughout the menstrual window. NSAIDs are a good choice when there is comorbid dysmenorrhea and allow for treatment of breakthrough headaches with triptans. Both strategies require that the timing of MM is highly predictable. Specific strategies for MM are those that reduce or eliminate the premenstrual decline in estradiol that predictably precipitates attacks. These include continuous or extended-cycle dosing of combined hormonal contraceptives (CHCs). A number of common gynecologic comorbidities argue for early adoption of these treatments, as CHCs effectively treat dysmenorrhea, menorrhagia, ovarian cysts, endometriosis, and irregular cycles. In the author's experience, hormonal preventives are the best approach for most women whose menstrual attacks are resistant to acute therapy. They afford the greatest therapeutic benefit in prevention while treating common comorbidities and allowing for acute treatment with triptans when needed. PMID- 22072056 TI - Treatment of nystagmus. AB - OPINION STATEMENT: Patients with congenital and acquired forms of nystagmus are commonly encountered in clinical practice. Many report visual symptoms, such as oscillopsia and blurred vision, which can be alleviated if the nystagmus can be suppressed. Pharmacologic, optical, and surgical treatments are available, with the choice of treatment depending on the characteristics of the nystagmus and the severity of the associated visual symptoms. Downbeat nystagmus can be treated with 4-aminopyridine, 3,4-diaminopyridine, or clonazepam. Upbeat nystagmus can be reduced with memantine, 4-aminopyridine, or baclofen. Torsional nystagmus may respond to gabapentin. Acquired pendular nystagmus in patients with multiple sclerosis is often partially suppressed by gabapentin or memantine. Acquired pendular nystagmus in patients with oculopalatal tremor can respond to gabapentin, memantine, or trihexyphenidyl. Although acquired periodic alternating nystagmus is often completely suppressed by baclofen, memantine can be effective in refractory cases. Seesaw nystagmus can be reduced with alcohol, clonazepam, or memantine. Infantile nystagmus may not cause significant visual symptoms if "foveation periods" are well developed, but the nystagmus can be treated in symptomatic patients with gabapentin, memantine, acetazolamide, topical brinzolamide, contact lenses, or base-out prisms to induce convergence. Several surgical therapies have also been reported to improve infantile nystagmus syndrome (INS), but selection of the appropriate therapy requires preoperative evaluation of visual acuity and nystagmus intensity in different gaze positions. Other treatment options for nystagmus include botulinum toxin injections into the extraocular muscles or retrobulbar space. Electro-optical devices are currently being developed, in order to noninvasively negate the visual consequences of nystagmus. PMID- 22072057 TI - Hypnic headache: clinical course and treatment. AB - OPINION STATEMENT: Thus far, no data from randomized placebo-controlled clinical trials are available for hypnic headache, so current treatment recommendations are based on single case reports and smaller open case series. In the predominantly elderly patient population affected by this disease, tolerability of the substances used is at least as important as their efficacy. Caffeine is the preferable first-line therapy for both acute treatment (i.e., a cup of strong coffee when awaking with headache) and prophylaxis (a cup of strong coffee before going to bed). Sleep problems should be considered as substantial side effects of this therapy, although they seem to occur far less than expected. For acute treatment, analgesics containing caffeine are also effective, but they may carry the risk of medication-overuse headache. Treatments that not effective for acute pain relief include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, 100% oxygen, and acetaminophen Triptans may be effective in single cases. For prophylaxis, lithium should be tried as a second treatment option if caffeine intake is not effective or tolerated. Lithium has been reported to be effective in many patients, but it was often discontinued because of side effects. Indomethacin may be a viable option for third-line prophylactic therapy. PMID- 22072058 TI - [Stability of volar fixed-angle plating for distal radius fractures. Failure modes in osteoporotic bone]. AB - BACKGROUND: Distal radius fractures continue to show significant complication rates after operative treatment with locked plating. Failure occurs by screw loosening or screw penetration in the distal fragment. Placement of additional screws may enhance the stiffness of fracture fixation. The aim of this study was to determine the fatigue properties of different screw configurations in distal radius plate osteosynthesis with biomechanical tests and finite element analysis (FEA). MATERIAL AND METHODS: Unstable distal radius fractures were created in 12 human cadaveric bone specimens and were fixed with volar locking plates. Group 4SC was fixed with four screws in the distal row and group 6SC with two additional screws the row below. Dynamic loading was applied physiologically. The radial shortening, the angulation of the distal fragment and the failure mechanism were determined by experimental tests and were further elucidated by FEA. RESULTS: Group 6SC showed a significantly lower radial shortening and inclination. Breakage of the screws within the plate was noted in group 4SC, while moderate screw penetration was observed in group 6SC. FEA confirmed the biomechanical tests. In group 4SC elevated von Mises strain in the locking mechanism explained the inclination of the screws and the distal fragment. The elastic strain in group 6SC was increased at the screw-bone interface which explained the resulting screw penetration. CONCLUSION: The failure mechanism in volar plating of distal radius fractures depended on the number of screws and their configuration. Using two more screws increases construct stiffness and angular stability under dynamic loading. However, increased stiffness also promoted screw penetration mainly in osteoporotic bone. Compared to screw penetration, loss of reposition and inclination of the distal fragment observed in the 4SC configuration is more likely to result in clinical complications. PMID- 22072059 TI - Airway exchange catheters: appropriate use and gas embolism. PMID- 22072060 TI - Unexplained fever after bilateral superficial cervical block in children undergoing cochlear implantation: an observational study. AB - PURPOSE: In an effort to decrease postoperative opioid requirements, intraoperative bilateral superficial cervical plexus block (BSCPB) was recently adopted for all our children undergoing general anesthesia for bilateral simultaneous cochlear implantation (BSiCI). Several cases of early postoperative fever were noted after the adoption of BSCPB. Our aim was to determine if an association exists between BSCPB and early postoperative fever in children undergoing BSiCI. As a secondary outcome, we studied the efficacy of BSCPB in altering postoperative analgesic requirements. METHODS: We conducted a retrospective cohort study of 91 consecutive children who underwent BSiCI. The series included 34 patients who received BSCPB (Block Group) and 57 patients who did not receive BSCPB (No-block Group). RESULTS: The median age (range) was 15.4 months (eight months - 15 yr). A significant association was found between BSCPB and postoperative fever (P = 0.006). Eighteen (19.7%) children developed fever in the first 24 hr after surgery (Block Group: 12/34 [35%]; No-block Group: 6/57 [11%]; P = 0.006). The Block Group was 4.8 times more likely to develop early postoperative fever after adjusting for other variables (P = 0.004). The Block Group spent more days in hospital after surgery compared with the No-block Group (P = 0.043). Other vital signs showed no major deviation from the normal ranges, and daily physical examinations revealed no obvious source of infection in children who developed postoperative fever. CONCLUSION: Bilateral superficial cervical plexus block may increase the risk of postoperative fever in children undergoing BSiCI. In this series, BSCPB was associated with a longer hospital admission. The etiology of the fever is undetermined, although it can be hypothesized that BSCPB resulted in unintended block of the phrenic nerves leading to diaphragmatic paralysis, atelectasis, and early postoperative fever in young children. PMID- 22072061 TI - Edaphic factors affecting the vertical distribution of radionuclides in the different soil types of Belgrade, Serbia. AB - The specific activities of natural radionuclides ((40)K, (226)Ra and (232)Th) and Chernobyl-derived (137)Cs were measured in soil profiles representing typical soil types of Belgrade (Serbia): chernozems, fluvisols, humic gleysols, eutric cambisols, vertisols and gleyic fluvisols. The influence of soil properties and content of stable elements on radionuclide distribution down the soil profiles (at 5 cm intervals up to 50 cm depth) was analysed. Correlation analysis identified associations of (40)K, (226)Ra and (137)Cs with fine-grained soil fractions. Significant positive correlations were found between (137)Cs specific activity and both organic matter content and cation exchange capacity. Saturated hydraulic conductivity and specific electrical conductivity were also positively correlated with the specific activity of (137)Cs. The strong positive correlations between (226)Ra and (232)Th specific activities and Fe and Mn indicate an association with oxides of these elements in soil. The correlations observed between (40)K and Cr, Ni, Pb and Zn and also between (137)Cs and Cd, Cr, Pb and Zn could be attributed to their common affinity for clay minerals. These results provide insight into the main factors that affect radionuclide migration in the soil, which contributes to knowledge about radionuclide behaviour in the environment and factors governing their mobility within terrestrial ecosystems. PMID- 22072063 TI - New 2011 survey of patients with complex care needs in eleven countries finds that care is often poorly coordinated. AB - Around the world, adults with serious illnesses or chronic conditions account for a disproportionate share of national health care spending. We surveyed patients with complex care needs in eleven countries (Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the United States) and found that in all of them, care is often poorly coordinated. However, adults seen at primary practices with attributes of a patient-centered medical home--where clinicians are accessible, know patients' medical history, and help coordinate care--gave higher ratings to the care they received and were less likely to experience coordination gaps or report medical errors. Throughout the survey, patients in Switzerland and the United Kingdom reported significantly more positive experiences than did patients in the other countries surveyed. Reported improvements in the United Kingdom tracked with recent reforms there in health care delivery. Patients in the United States reported difficulty paying medical bills and forgoing care because of costs. Our study indicates a need for improvement in all countries through redesigning primary care, developing care teams accountable across sites of care, and managing transitions and medications well. The United States in particular has opportunities to learn from diverse payment innovations and care redesign efforts under way in the other study countries. PMID- 22072062 TI - ER stress sensitizes cells to TRAIL through down-regulation of FLIP and Mcl-1 and PERK-dependent up-regulation of TRAIL-R2. AB - Despite recent evidences suggesting that agents inducing endoplasmic reticulum (ER) stress could be exploited as potential antitumor drugs in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), the mechanisms of this anticancer action are not fully understood. Moreover, the effects of ER stress and TRAIL in nontransformed cells remain to be investigated. In this study we report that ER stress-inducing agents sensitizes both transformed and nontransformed cells to TRAIL-induced apoptosis. In addition, glucose-regulated protein of 78 kDa (GRP78) knockdown by RNA interference induces ER stress and facilitates apoptosis by TRAIL. We demonstrate that TRAIL death-inducing signaling complex (DISC) formation and early signaling are enhanced in ER stressed cells. ER stress alters the cellular levels of different apoptosis related proteins including a decline in the levels of FLIP and Mcl-1 and the up regulation of TRAIL-R2. Up-regulation of TRAIL-R2 following ER stress is dependent on the expression of PKR-like ER kinase (PERK) and independent of CAAT/enhancer binding protein homologous protein (CHOP) and Ire1alpha. Silencing of TRAIL-R2 expression by siRNA blocks the ER stress-mediated sensitization to TRAIL-induced apoptosis. Furthermore, simultaneous silencing of cFLIP and Mcl-1 expression by RNA interference results in a marked sensitization to TRAIL-induced apoptosis. Finally, in FLIP-overexpressing cells ER stress-induced sensitization to TRAIL-activated apoptosis is markedly reduced. In summary, our data reveal a pleiotropic mechanism involving both apoptotic and anti-apoptotic proteins for the sensitizing effect of ER stress on the regulation of TRAIL receptor-mediated apoptosis in both transformed and nontransformed cells. PMID- 22072064 TI - Interplay between gold nanoparticle biosynthesis and metabolic activity of cyanobacterium Synechocystis sp. PCC 6803. PMID- 22072065 TI - Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. AB - BACKGROUND: Tools are lacking to assess the individual risk of severe toxicity from chemotherapy. Such tools would be especially useful for older patients, who vary considerably in terms of health status and functional reserve. METHODS: The authors conducted a prospective, multicentric study of patients aged >=70 years who were starting chemotherapy. Grade 4 hematologic (H) or grade 3/4 nonhematologic (NH) toxicity according to version 3.0 of the Common Terminology Criteria for Adverse Events was defined as severe. Twenty-four parameters were assessed. Toxicity of the regimen (Chemotox) was adjusted using an index to estimate the average per-patient risk of chemotherapy toxicity (the MAX2 index). In total, 562 patients were accrued, and 518 patients were evaluable and were split randomly (2:1 ratio) into a derivation cohort and a validation cohort. RESULTS: Severe toxicity was observed in 64% of patients. The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score was constructed along 2 subscores: H toxicity and NH toxicity. Predictors of H toxicity were lymphocytes, aspartate aminotransferase level, Instrumental Activities of Daily Living score, lactate dehydrogenase level, diastolic blood pressure, and Chemotox. The best model included the 4 latter predictors (risk categories: low, 7%; medium-low, 23%; medium-high, 54%; and high, 100%, respectively; P(trend) < .001). Predictors of NH toxicity were hemoglobin, creatinine clearance, albumin, self-rated health, Eastern Cooperative Oncology Group performance, Mini-Mental Status score, Mini Nutritional Assessment score, and Chemotox. The 4 latter predictors provided the best model (risk categories: 33%, 46%, 67%, and 93%, respectively; P(trend) < .001). The combined risk categories were 50%, 58%, 77%, and 79%, respectively; P(trend) < .001). Bootstrap internal validation and independent sample validation demonstrated stable risk categorization and P(trend) < .001. CONCLUSIONS: The CRASH score distinguished several risk levels of severe toxicity. The split score discriminated better than the combined score. To the authors' knowledge, this is the first score systematically integrating both chemotherapy and patient risk for older patients and has a potential for future clinical application. PMID- 22072066 TI - Iatrogenic psychological harm. AB - While prevention of iatrogenic harm is a sufficient priority to determine service structures and practice, the concept of harm is largely restricted to the physical. Psychological harm has received scant attention despite its importance, particularly for children and adolescents. A professional climate increasingly reliant on measurement and evidence and coloured by fear of litigation contributes to perpetuating the anomaly. The aim of this paper is to consider how and why iatrogenic psychological harm may happen, why i-dt matters, how it may be manifest and how it may be prevented. Prevention of psychological harm should be as great a priority as that of physical harm. PMID- 22072067 TI - In vitro and in vivo assessment of the glycemic index of bakery products: influence of the reformulation of ingredients. AB - PURPOSE: To evaluate whether the modification of ingredients of two bakery products, muffins and bread, reduces their glycemic index, by means of in vitro and in vivo procedures. METHODS: In vitro and in vivo glycemic index were evaluated for two types of bread and two types of muffins including one standard product for each category. For the in vitro determination, kinetics of starch digestion method was used. For the in vivo procedure, postprandial glucose measured as IAUC was obtained in a group of eighteen healthy volunteers (ten did the test with muffins and eight with breads). RESULTS: In in vitro, a reduction in the expected glycemic index regarding the control muffin was achieved with the partial substitution of wheat flour by a mixture of resistant starch, dextrin and lentil flour. In breads, with the partial substitution of wheat flour by a mixture of resistant starch and dextrins, a decrease in the expected glycemic index was also observed. In in vivo, a reduction in GI was also achieved both in muffin and in bread. All the obtained GI was higher in in vitro method. CONCLUSIONS: Despite the fact that in vitro overestimate in vivo method, the trend in the reduction in GI seems to be similar in both methods. With the substitution assayed, a reduction in the expected glycemic index and the glycemic index were obtained both in muffins and in breads. PMID- 22072068 TI - The recombination landscape in Arabidopsis thaliana F2 populations. AB - Recombination during meiosis shapes the complement of alleles segregating in the progeny of hybrids, and has important consequences for phenotypic variation. We examined allele frequencies, as well as crossover (XO) locations and frequencies in over 7000 plants from 17 F(2) populations derived from crosses between 18 Arabidopsis thaliana accessions. We observed segregation distortion between parental alleles in over half of our populations. The potential causes of distortion include variation in seed dormancy and lethal epistatic interactions. Such a high occurrence of distortion was only detected here because of the large sample size of each population and the number of populations characterized. Most plants carry only one or two XOs per chromosome pair, and therefore inherit very large, non-recombined genomic fragments from each parent. Recombination frequencies vary between populations but consistently increase adjacent to the centromeres. Importantly, recombination rates do not correlate with whole-genome sequence differences between parental accessions, suggesting that sequence diversity within A. thaliana does not normally reach levels that are high enough to exert a major influence on the formation of XOs. A global knowledge of the patterns of recombination in F(2) populations is crucial to better understand the segregation of phenotypic traits in hybrids, in the laboratory or in the wild. PMID- 22072069 TI - Genetic correlations and the evolution of photoperiodic time measurement within a local population of the pitcher-plant mosquito, Wyeomyia smithii. AB - The genetic relationship between the daily circadian clock and the seasonal photoperiodic timer remains a subject of intense controversy. In Wyeomyia smithii, the critical photoperiod (an overt expression of the photoperiodic timer) evolves independently of the rhythmic response to the Nanda-Hamner protocol (an overt expression of the daily circadian clock) over a wide geographical range in North America. Herein, we focus on these two processes within a single local population in which there is a negative genetic correlation between them. We show that antagonistic selection against this genetic correlation rapidly breaks it down and, in fact, reverses its sign, showing that the genetic correlation is due primarily to linkage and not to pleiotropy. This rapid reversal of the genetic correlation within a small, single population means that it is difficult to argue that circadian rhythmicity forms the necessary, causal basis for the adaptive divergence of photoperiodic time measurement within populations or for the evolution of photoperiodic time measurement among populations over a broad geographical gradient of seasonal selection. PMID- 22072071 TI - Non-contrast MRA using an inflow-enhanced, inversion recovery SSFP technique in pediatric abdominal imaging. AB - Abdominal contrast-enhanced MR angiography (CE-MRA) is routinely performed in children. CE-MRA is challenging in children because of patient motion, difficulty in obtaining intravenous access, and the inability of young patients to perform a breath-hold during imaging. The combination of pediatric-specific difficulties in imaging and the safety concerns regarding the risk of gadolinium-based contrast agents in patients with impaired renal function has renewed interest in the use of non-contrast (NC) MRA techniques. At our institution, we have optimized 3-D NC MRA techniques for abdominal imaging. The purpose of this work is to demonstrate the utility of an inflow-enhanced, inversion recovery balanced steady-state free precession-based (b-SSFP) NC-MRA technique. PMID- 22072070 TI - Making a long story short: noncoding RNAs and chromosome change. AB - As important as the events that influence selection for specific chromosome types in the derivation of novel karyotypes, are the events that initiate the changes in chromosome number and structure between species, and likewise polymorphisms, variants and disease states within species. Although once thought of as transcriptional 'noise', noncoding RNAs (ncRNAs) are now recognized as important mediators of epigenetic regulation and chromosome stability. Here we highlight recent work that illustrates the influence short and long ncRNAs have as participants in the function and stability of chromosome regions such as centromeres, telomeres, evolutionary breakpoints and fragile sites. We summarize recent evidence that ncRNAs can facilitate chromosome change and present mechanisms by which ncRNAs create DNA breaks. Finally, we present hypotheses on how they may create novel karyotypes and thus affect chromosome evolution. PMID- 22072072 TI - Complex cloacal malformations: use of rotational fluoroscopy and 3-D reconstruction in diagnosis and surgical planning. AB - A cloacal malformation is a congenital malformation in which the urinary tract, gynecological system and distal rectum fail to separate and form a common channel with a single perineal opening. Precise anatomical information is required to plan surgery and predict prognosis for children with this abnormality. Conventional fluoroscopic studies provide limited information, primarily due to the overlap of structures and inability to make accurate measurements. Rotational fluoroscopy and 3-D reconstruction help clarify overlapping structures and allow for precise measurement of the common channel, thereby helping to predict the complexity of the surgical case as well as the long-term prognosis regarding bowel, bladder and sexual function. PMID- 22072073 TI - Mitochondrial dysfunction in familial amyotrophic lateral sclerosis. AB - A growing body of evidence suggests that mitochondrial dysfunctions play a crucial role in the pathogenesis of various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting both upper and lower motor neurons. Although ALS is predominantly a sporadic disease, approximately 10% of cases are familial. The most frequent familial form is caused by mutations in the gene encoding Cu/Zn superoxide dismutase 1 (SOD1). A dominant toxic gain of function of mutant SOD1 has been considered as the cause of the disease and mitochondria are thought to be key players in the pathogenesis. However, the exact nature of the link between mutant SOD1 and mitochondrial dysfunctions remains to be established. Here, we briefly review the evidence for mitochondrial dysfunctions in familial ALS and discuss a possible link between mutant SOD1 and mitochondrial dysfunction. PMID- 22072074 TI - Site-specific protein double labeling by expressed protein ligation: applications to repeat proteins. AB - In the last few years, the use of labeled proteins has significantly expanded in the life sciences. Now, labeled proteins are indispensable tools for a wide spectrum of biophysical and chemical biology applications. In particular, the quest for more sophisticated experimental setups requires the development of new synthetic methodology, especially for multiple site-specific labeling. In this paper, we describe a synthetic strategy based on expressed protein ligation to prepare proteins in high purity and homogeneity, in which two different molecular probes are incorporated specifically at any desired position. Proteins are sequentially labeled in solution, with the advantage that a large excess of probes is not required and the labeled fragments are not restricted to peptide synthesis length limitations. This strategy was applied to selectively label a repeat protein with a fluorophores pair in different positions along the protein sequence. The doubly labeled proteins were prepared at high purity and homogeneity, as required for single molecule FRET studies. Remarkably, this approach can be adapted to the introduction of more than two molecular probes. PMID- 22072075 TI - Age, genotype and sex effects on growth performance of local chickens kept under improved management in Ghana. AB - Characterisation of animal genetic resources has been recognised globally as an important step towards their sustainable use. Body weight data of local chickens (213 forest and 160 savannah chickens) and 183 French free-ranging SASSO T44 chickens kept under improved management were collected from hatch to 40 weeks of age and analysed to determine the effects of age, genotype and sex on their growth performance. At all ages, SASSO T44 chickens had significantly (P<0.05) higher weights (2.6-3.2 kg at 28 weeks) than the local chickens (1.2-1.7 kg at 28 weeks). The rate of growth at the earlier ages in the local genotypes (5.57-7.80 g/day) was lower than the range of 13.81-15.42 in SASSO T44 chickens. Except at hatch, savannah chickens were significantly heavier (P<0.05) than the forest chickens at all ages. Male chickens had significantly (P<0.05) superior growth rates than females across all genotypes except from the 20th to the 28th week. Growth trends in both sexes depicted linear increase in body weights; however, the rate of increase in body weights was higher in males as compared to females, thus showing clear sexual dimorphism. There were no significant (P>0.05) differences in the growth rates of SASSO T44 chickens and local genotypes at the later ages (20-28 weeks). Local chickens from the savannah zone had better growth rate than forest chickens. The significant effect of ecozone on the growth potential of local chickens is an indication that their productive potential could be improved through interventions in the environment such as provision of feed and some veterinary care. PMID- 22072076 TI - Effect of carbohydrate sources and cotton seed meal in the concentrate: II. Feed intake, nutrient digestibility, rumen fermentation and microbial protein synthesis in beef cattle. AB - Four, rumen fistulated crossbred (Brahman * native) beef cattle steers were randomly assigned to receive four dietary treatments according to a 2 * 2 factorial arrangement in a 4 * 4 Latin square design. Factor A was carbohydrate source; cassava chip (CC) or CC + rice bran at a ratio 3:1 (CR3:1) and Factor B was cotton seed meal level (CM); and 109 g CP/kg (LCM) and 328 g CP/kg (HCM) at similar overall CP levels (490 g CP/kg). The animals were fed 5 g concentrate/kg BW, and urea-treated rice straw (UTS) (50 g urea/kg DM) was fed ad libitum. Carbohydrate source did not affect feed intake, nutrient digestibility, blood urea nitrogen, rumen fermentation, or microbial protein synthesis; however, animals fed with CC had a higher population of total viable bacteria than the CR3:1 treatment (P<0.05). Animals that received HCM had a lower total feed intake while ruminal pH was higher than the LCM fed treatment (P<0.05). The population of total viable and cellulolytic bacteria in animals that received HCM were lower than the LCM fed treatment (P<0.05). Moreover, use of HCM in beef cattle diets resulted in lower microbial protein synthesis when compared with the LCM fed treatment (P<0.05) although efficiency of microbial protein synthesis was nonsignificantly different among treatments. Therefore, cassava chip combined with rice bran can be used in a concentrate diet for beef cattle. It is also noted that a high level of cotton seed meal in the concentrate may impact rumen fermentation and animal performance. PMID- 22072077 TI - Effects of double transport and season on sensorial aspects of lamb's meat quality in dry climates. AB - The objective of the current study was to analyse the effects of double transport and season on sensorial aspects of lamb's meat quality in dry climates. A total of 144 lambs were sampled in a 3 * 2 * 2 factorial design, testing three types of double transport along the residence time at a pre-slaughter classification centre or CC (0, 7 and 28 days) and two seasons (summer and winter), with two replicates in each season. Meat from the M. longissimus was analysed in terms of pH and WHC and tasted by a trained sensory panel in terms of lamb odour intensity, tenderness, juiciness, lamb flavour intensity, fat flavour intensity, liver flavour intensity, metallic flavour intensity and overall liking. Meat sensorial quality traits were not significantly affected by double transport. Season had a significant (P<0.001) effect on all variables analysed, except for lamb flavour intensity and overall liking. Interactions between the fixed effects were not significant, with the exception of tenderness. Season significantly affects several sensorial variables, and they seem to be independent of double transport, with the exception of tenderness. PMID- 22072078 TI - FEM assisted evaluation of PMMA and Ti6Al4V as materials for cranioplasty resulting mechanical behaviour and the neurocranial protection. AB - Recent advances in Computer Aided Design and Manufacturing techniques (CAD/CAM) have facilitated the rapid and precise construction of customized implants used for craniofacial reconstruction. Data of the patients' trauma, acquired through Computer Topographies (CT), provide sufficient information with regard to the defect contour profile, thus allowing a thorough preoperative evaluation whilst ensuring excellent implant precision. During the selection, however, of a suitable implant material for the specific trauma, the mechanical aspects of the implant have to be considered. This investigation aims to assess the mechanical strength, the shock resistance and the critical deflection of cranial implants manufactured with two commonly used materials, Polymethylmethacrylate (PMMA) and Ti6Al4V. Even though the strength properties of Ti-alloys are far superior to those of PMMA, there are several aspects that may act in advantage of PMMA, e.g., it is known that discontinuities in the elastic modulus of adjoined parts (bone implant) lead to bone resorption thus loosening the fixation of the implant over time.The implant design and fixation was the same in both cases allowing a direct comparison of the implant behavior for various loads. Finite Element Methods (FEM) assisted procedures were employed, providing a valuable insight to the neurocranial protection granted by these implants. PMID- 22072079 TI - Nano-vibration effect on cell adhesion and its shape. AB - Extracellular physical features of underlying the adhesive substrate affect cell adhesion to it substrate. In this study, the effects of vibration, a type of artificial physical stimulation, on the adhesion of mouse L929 cells, mouse embryonic fibroblasts (MEFs), HeLa cells and human umbilical vein endothelial cells (HUVECs) are reported. A nano-vibration system was designed to produce nanometer-scale vibration. When L929 cells, HeLa cells, and HUVECs were subjected to vibration at 100 Hz and 1 kHz, they were not affected. On the other hand, in MEFs, the adherent cells were increased and changed their shape remarkably in response to 1 kHz vibration. To investigate the MEFs' sensitivity to vibration in detail, the cells shape was classified into four types; round, stellate, filopodia-formed and lamellipodia-formed. In serum addition culture, 1 kHz vibration increased the number of filopodia-formed cells but decreased lamellipodia cells. Furthermore, the preliminary cDNA microarray experiments showed that expression of genes which regulate cytoskeleton were changed by vibration stimulation. These results suggest that vibration could affect cell adhesion and the determination cell shape. PMID- 22072080 TI - Effect of calcium alginate concentration on viability and proliferation of encapsulated fibroblasts. AB - Alginate hydrogels have been used widely in tissue engineering for cell encapsulation for several reasons: low toxicity, the ability to gel under gentle condition and compatibility with cells. In this study, we determined the effect of different concentrations of alginate on encapsulation of 3T3 fibroblast cells at two different cell seeding densities. Live/dead staining and MTT assay were performed at regular intervals up to 4 weeks. A Hoechst 33258 assay was done to validate the MTT results. There were more dead cells on day 1 for the higher concentrations of alginate while at, the lower concentration of alginate, cell proliferation and spheroid formation occurred more quickly. Furthermore, at low cell seeding density, cell proliferation was prolonged compared to the intermediate seeding density. In conclusion, by altering both alginate concentration and cell seeding density, proliferation and spheroid formation can be controlled. PMID- 22072081 TI - Frequency response of blood vessel wall with atherosclerosis and aneurysm. AB - This research was conducted to investigate frequency response of blood vessel wall. The principal frequency of blood vessel wall, f1 was found to decrease with progression of atherosclerosis and irregularity of the vibration trajectory of blood vessel wall was found to increase. When an aneurysm appeared, a new vibration wave was found to appear in the high frequency region, f2. When the aneurysm wall has enough strength, intensity of high frequency wave was found to increase. However, it decreases with decrease in the strength of aneurysm wall. The visco-elastic deterioration of blood vessel wall was found to well correlate with the changing characteristics of f1. A two-dimensional representation of f1 and f2 was conducted which tracks the progression of atherosclerosis and aneurysm. It will enable us to diagnose the introduction period of operation of blood vessel wall of atherosclerosis with an aneurysm. PMID- 22072082 TI - Characterization of a hydroxyapatite sputtered film subject to hydrothermal treatment using FE-SEM and STEM. AB - Hydroxyapatite (HA) was coated onto a titanium substrate using radio frequency magnetron sputtering. The sputtered film was crystallized using a hydrothermal treatment. The films were observed using X-ray diffractometry, field emission scanning electron microscopy (FE-SEM) and scanning transmission electron microscopy (STEM) equipped with energy dispersive X-ray spectroscopy (EDX).It was observed that the surface of the hydrothermally-treated film was covered with globular particles. The FE-SEM observations indicated that these particles were composed of columnar grains with a grain size of 20-50 nm. In the STEM cross sectional observation of the HA-Ti interface, HA crystalline phase regions were observed, in part, in the non-crystalline phase layer of the as-sputtered film. After the hydrothermal treatment, the HA layer crystallized; the HA crystallization proceeded to a distance of 30 nm above the titanium surface. From an EDX line scan analysis, the titanium oxide layer was not observed at the HA-Ti interface of the as-sputtered film; however, in the hydrothermally-treated film, the titanium oxide layer, with a 15 nm thickness, was observed between the mixing layer and the titanium substrate. The formation of titanium oxide at the HA-Ti interface would contribute to the adhesion improvement of the sputtered film following the hydrothermal treatment. PMID- 22072084 TI - Construct validity and reliability of ultrasound disease activity score in assessing joint inflammation in RA: comparison with DAS-28. AB - OBJECTIVE: To investigate the construct validity and reliability of US DAS compared with 28-joint DAS (DAS-28) in assessing joint inflammation and in prediction of structural damage in patients with RA. METHODS: Ninety patients with active RA were prospectively recruited and followed up during the 6 months of treatment. The patients underwent clinical, laboratory and X-ray assessment, along with blinded power Doppler US (PDUS) and grey-scale (GS) US (GSUS) examination at baseline and 6 months. A subgroup of 25/90 randomly assigned patients underwent MRI examination of their hands at baseline. A PDUS examination of 22 joints and GSUS examination for effusion/hypertrophy (E/H) of 28 joints were performed by two independent examiners, blinded to clinical findings. E/H was qualitatively assessed as absent or present, and PD signal was semi quantitatively graded from 0 to 3. PDUS score for synovitis in 22 joints and GS score for E/H in 28 joints were included in US DAS calculation. Clinical scoring, PDUS and GSUS inter-observer reliability were evaluated. RESULTS: Strong correlation was found between US DAS and standard assessment of disease activity such as the DAS-28, ESR and CRP levels. Correlation between US DAS and patients' and physicians' visual analogue scale of activity was moderate, whereas correlations of US DAS with Health Assessment Questionnaire - Disability Index (HAQ-DI) and Short Form 36 Health Survey (SF-36) were weak to moderate. US DAS correlated with X-ray, MRI and US parameters and rates of joint damage. CONCLUSION: US DAS better anticipated future joint damage than standard DAS-28. PMID- 22072085 TI - Investigation of prognostic factors for skin sclerosis and lung function in Japanese patients with early systemic sclerosis: a multicentre prospective observational study. AB - OBJECTIVE: To clarify the clinical course of SSc in Japanese patients with early onset disease. It is well known that ethnic variations exist in the clinical features and severity of SSc. However, neither the clinical course nor prognostic factors have been thoroughly investigated in the Japanese population. METHODS: Ninety-three Japanese patients of early-onset SSc (disease duration: <3 years) with diffuse skin sclerosis and/or interstitial lung disease were registered in a multi-centre observational study. All patients had a physical examination with laboratory tests at their first visit and at each of the three subsequent years. Factors that could predict the severity of skin sclerosis and lung involvement were examined statistically by multiple regression analysis. RESULTS: Two patients died from SSc-related myocardial involvement and four patients died from other complications during the 3-year study. Among various clinical data assessed, the initial modified Rodnan total skin thickness score (MRSS) and maximal oral aperture were associated positively and negatively with MRSS at Year 3, respectively. Additionally, initial ESR tended to be associated with final MRSS. Pulmonary vital capacity (VC) in the third year was significantly associated with initial %VC. Furthermore, patients with anti-topo I antibody tended to show reduced %VC at Year 3. CONCLUSIONS: Several possible prognostic factors for skin sclerosis and lung function were detected in Japanese patients with early SSc. Further longitudinal studies of larger populations will be needed to confirm these findings. PMID- 22072086 TI - Negative predictive value of intravenous contrast-enhanced CT of the abdomen for patients presenting to the emergency department with undifferentiated upper abdominal pain. AB - The purpose of this study is to calculate the negative predictive value (NPV) CT of the abdomen in patients presenting to the emergency department (ED) with undifferentiated upper abdominal pain. Approved by the hospital research ethics board, this retrospective study examined consecutive patients presenting to the ED with undifferentiated upper abdominal pain whose intravenous contrast-enhanced CT of the abdomen was reported as "normal" from June 2006-August 2010. Exclusion criteria included active malignancy, trauma, and known inflammatory bowel disease. True-negative (TN) vs. false-negative (FN) cases were categorized by consensus opinion of radiologist and emergency physician using a composite reference standard including clinical, laboratory, imaging, surgery, pathology, and patient self-reporting via phone questionnaire. The NPV was calculated with confidence intervals of 95%. The TN and FN groups were compared based on gender, age, site of pain, oral contrast use, and laboratory values. One hundred twenty seven patients were included for analysis. The NPV was 64% (95% CI 55-72). The FN group had a higher proportion of patients with epigastric pain (p = 0.02) and a lower proportion of patients with left upper quadrant pain (p = 0.02). The WBC, lipase, and ALT were all higher in the FN group compared with the TN group. The most commonly missed pathologies were inflammatory conditions of the biliary tract and upper gastrointestinal systems. The NPV of CT for evaluation of undifferentiated upper abdominal pain in the ED was low at 64%. Physicians should consider this limitation and the commonly missed pathology when discharging patients with a "normal" CT report. PMID- 22072087 TI - Imaging of acute right lower quadrant abdominal pain: differential diagnoses beyond appendicitis. AB - Evaluation of acute right lower quadrant pain remains a common and challenging clinical scenario for emergency medicine physicians due to frequent nonspecific signs, symptoms, and physical examination findings. Therefore, imaging has evolved to play a pivotal role in the emergency setting. While appendicitis is a common cause for acute pain, there are numerous other important differential considerations with which the radiologist must be aware. The purpose of this review is to list an anatomy-based, encompassing differential diagnosis in addition to acute appendicitis for right lower quadrant pain; demonstrate the key imaging findings of numerous differential considerations; and describe helpful imaging and clinical features useful in narrowing the differential diagnosis. PMID- 22072088 TI - Prognostic importance of preoperative anti-PF4/heparin antibodies in patients undergoing cardiac surgery. A systematic review. AB - It was the objective of this study to obtain best estimates of the prevalence of anti-PF4/heparin antibodies in patients not suspected to have clinical heparin induced thrombocytopenia (HIT) prior to undergoing cardiac surgery and to determine whether preoperative antibody status and antibody class is predictive of postoperative thromboembolic outcomes, non-thromboembolic outcomes, length of stay, and mortality. PubMed and EMBASE online databases were searched up to July 2011, and we included studies involving adults undergoing cardiac surgery examining the relationship between preoperative anti-PF4/heparin antibodies (ELISA) and postoperative clinical outcomes. Five studies involving a combined total of 2,332 patients met our inclusion criteria. Preoperative anti-PF4/heparin antibodies were detected in 5-22% of patients. No study demonstrated an association between preoperative anti-PF4/heparin antibodies and postoperative thromboembolic outcomes or mortality. Three studies demonstrated a statistically significant association between preoperative anti-PF4/heparin antibodies and length of stay while two showed an association with non-thromboembolic complications. In the one study that examined outcomes by anti-PF4/heparin antibody class, IgM antibodies predicted non-thromboembolic complications and length-of-stay. None of the studies reported prior heparin exposure, and most studies did not examine the relationship of the absolute value of antibody titres (ELISA OD) and risk, nor the incidence of true/clinical HIT in preoperative positive or negative patients. In conclusion, pre-formed anti-PF4/heparin antibodies are common in patients undergoing cardiac surgery, but the available literature does not support that they predict postoperative thromboembolic complications or death. There does appear to be an association between anti PF4/heparin antibodies and non-thromboembolic adverse events, but a causal relationship is unlikely. PMID- 22072089 TI - The EXCITE Trial: analysis of "noncompleted" Wolf Motor Function Test items. AB - OBJECTIVE: This is the first study to examine Wolf Motor Function Test (WMFT) tasks among EXCITE Trial participants that could not be completed at baseline or 2 weeks later. METHODS: Data were collected from participants who received constraint-induced movement therapy (CIMT) immediately at the time of randomization (CIMT-I, n = 106) and from those for whom there was a delay of 1 year in receiving this intervention (CIMT-D, n = 116). Data were collected at baseline and at a 2-week time point, during which the CIMT-I group received the CIMT intervention and the CIMT-D group did not. Generalized estimating equation (GEE) analyses were used to examine repeated binary data and count values. Group and visit interactions were assessed, adjusting for functional level, affected side, dominant side, age, and gender covariates. RESULTS: In CIMT-I participants, there was an increase in the proportion of completed tasks at posttest compared with CIMT-D participants, particularly with respect to those tasks requiring dexterity with small objects and total incompletes (P < .0033). Compared with baseline, 120 tasks governing distal limb use for CIMT-I and 58 tasks dispersed across the WMFT for CIMT-D could be completed after 2 weeks. Common movement components that may have contributed to incomplete tasks include shoulder stabilization and flexion, elbow flexion and extension, wrist pronation, supination and ulnar deviation, and pincer grip. CONCLUSION: CIMT training should emphasize therapy for those specific movement components in patients who meet the EXCITE criteria for baseline motor control. PMID- 22072090 TI - Case files of the Emory University Medical Toxicology Fellowship: inhalational mercury toxicity from a traditional Vietnamese product. PMID- 22072091 TI - Advanced molecular biologic techniques in toxicologic disease. AB - The advancement of molecular biologic techniques and their capabilities to answer questions pertaining to mechanisms of pathophysiologic events have greatly expanded over the past few years. In particular, these opportunities have provided researchers and clinicians alike the framework from with which to answer clinical questions not amenable for elucidation using previous, more antiquated methods. Utilizing extremely small molecules, namely microRNA, DNA, protein, and nanoparticles, we discuss the background and utility of these approaches to the progressive, practicing physician. Finally, we consider the application of these tools employed as future bedside point of care tests, aiding in the ultimate goal of unsurpassed patient care. PMID- 22072092 TI - Orthopaedic case of the month: lower leg pain in a 41-year-old woman. PMID- 22072094 TI - Drug and device trials: should we ask more. PMID- 22072093 TI - Is a positive clinical outcome after exercise therapy for chronic non-specific low back pain contingent upon a corresponding improvement in the targeted aspect(s) of performance? A systematic review. AB - INTRODUCTION: The effect size for exercise therapy in the treatment of chronic non-specific low back pain (cLBP) is only modest. This review aims to analyse the specificity of the effect by examining the relationship between the changes in clinical outcome (pain, disability) and the changes in the targeted aspects of physical function (muscle strength, mobility, muscular endurance) after exercise therapy. METHODS: We searched for exercise therapy trials for cLBP published up to 15 April 2010 in Medline, Embase, Cochrane Library, Cinahl, and PEDro. Two independent reviewers selected studies according to the inclusion criteria. DATA EXTRACTION: one author extracted the data of the articles. RESULTS: DATA SYNTHESIS: 16 studies with a total of 1,476 participants met the inclusion criteria. There was little evidence supporting a relationship between the changes in pain or physical function and the changes in performance for the following measures: mobility (no correlation in 9 studies, weak correlation in 1 study), trunk extension strength (7 and 2, respectively), trunk flexion strength (4 and 1, respectively) and back muscle endurance (7 and 0, respectively). Changes in disability showed no correlation with changes in mobility in three studies and a weak correlation in two; for strength, the numbers were four (no correlation) and two (weak correlation), respectively. CONCLUSIONS: The findings do not support the notion that the treatment effects of exercise therapy in cLBP are directly attributable to changes in the musculoskeletal system. Future research aimed at increasing the effectiveness of exercise therapy in cLBP should explore the coincidental factors influencing symptom improvement. PMID- 22072096 TI - The impact of comorbidities on stroke prophylaxis strategies in atrial fibrillation patients. AB - Arial fibrillation (AF) is the most commonly occurring sustained arrhythmia in the United States and is associated with increased mortality. AF is a risk factor for ischemic stroke, and risk factors for AF include comorbid conditions such as congestive heart failure, diabetes mellitus, older age, hypertension, diabetes, pulmonary disease, and history of stroke, transient ischemic attack, or heart failure. Risk stratification for ischemic stroke in AF patients is based on scoring a group of risk factors that allows for the appropriate tailoring of antithrombotic therapy. The vitamin K antagonists are effective at reducing ischemic stroke rates in medium-risk to high-risk patients and are therefore generally recommended for this group. However, a large proportion of these patients are not treated with vitamin K antagonists because of the potential for adverse outcomes, particularly in elderly patients. New direct thrombin inhibitors and direct Factor Xa inhibitors in development offer the possibility of simplifying treatment and management although offering similar or better efficacy and safety profiles to warfarin. In light of these potential new treatments, the importance and improvement of risk stratification methods and the resulting recommendations in thromboprophylaxis become even more paramount as they make it more likely that medium-risk to high-risk patients can be treated safely. PMID- 22072097 TI - Characteristics of surface ozone at an urban site of Xi'an in Northwest China. AB - Surface ozone concentrations in Xi'an, China were monitored from March 23, 2008 to January 12, 2009 using the Model ML/EC9810 ozone analyzer. The daily average O(3) ranged from <1 ppb to 64.2 ppbv with an annual average of 16.0 ppbv. The seasonal average of O(3) in summer (32.5 ppbv) was more than 10 times higher than that in winter (3.0 ppbv). A significant positive correlation was found between ozone concentration and ambient temperature, indicating that the intensity of solar radiation was one of the several major factors controlling surface ozone production. Using the NOAA HYSPLIT 4 trajectory model, the three longest O(3) pollution episodes were found to be associated with the high biogenic volatile organic carbon (BVOC) emissions from the vegetation of Qinling Mountains. No significant weekday and weekend difference in O(3) levels was detected due to the non-significant change in NO(x) emissions. O(3) depletion by NO emission directly emitted from vehicles, low oxygenated VOC concentrations, and low-level solar radiation caused by high aerosol loading all contributed to the low levels of O(3) found in Xi'an compared to other cities and rural areas. PMID- 22072098 TI - Polarization dependent solar cell conversion efficiency at oblique incident angles and the corresponding improvement using surface nanoparticle coating. AB - Despite tremendous efforts on improving the solar cell conversion efficiency at normal incidence, improvement at oblique angles has not been widely addressed, not to mention the corresponding light absorption behaviors at different polarizations. Here we report the characterization of the solar cell conversion efficiency and the spectra of photoresponsivity at various tilted angles. The results show that TM (transverse magnetic) polarized light possesses higher photoresponsivity than TE (transverse electric) polarized light and the difference becomes larger with the incidence angle. To address the issue, a monolayer of silica nanoparticles on the solar cell surface was employed to improve the light absorption. Even though both TE and TM waves show a decrease in the surface reflectivity with the presence of nanoparticles, the interaction between the silica particles and the TE wave is more significant. The improvement of the conversion efficiency for obliquely incident light is explained from the refractive index difference of the nanoparticles for the TE and TM polarizations. PMID- 22072099 TI - Therapeutic efficacy of combination therapy with intra-arterial 5-fluorouracil and systemic pegylated interferon alpha-2b for advanced hepatocellular carcinoma with portal venous invasion. AB - BACKGROUND: The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly among patients with portal vein tumor thrombosis (PVTT). This study evaluated the efficacy of combined 5-fluorouracil and pegylated interferon (PEG-IFN) alpha-2b in patients with advanced HCC. METHODS: Subjects comprised 59 HCC patients with PVTT treated using subcutaneous administration of PEG-IFNalpha 2b (50-100 MUg on day 1 of each week for 4 weeks) and intra-arterial infusion of 5-fluorouracil (250 mg/d for 5 hours on days 1-5 of each week for 4 weeks). One treatment cycle lasted 4 weeks. The current therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for >=1 cycle. The primary efficacy endpoint was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival. RESULTS: Objective early response rate was 73.0%. Cumulative PFS rates were 67.4% at 6 months, 30.2% at 12 months, 25.9% at 18 months, and 20.7% at 24 months. Median PFS was 9.7 months. Cumulative survival rates were 82.4% at 6 months, 73.6% at 12 months, 52.8% at 24 months, and 44.0% at 36 months. Median survival time was 29.9 months. All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment-related deaths were not observed. CONCLUSIONS: Although a prospective randomized controlled trial using a larger population of patients with advanced HCC is needed to evaluate combination therapy with 5-fluorouracil and PEG IFNalpha-2b, this new combination therapy may be useful for patients with advanced HCC. PMID- 22072100 TI - An integrated genetic linkage map of cultivated peanut (Arachis hypogaea L.) constructed from two RIL populations. AB - Construction and improvement of a genetic map for peanut (Arachis hypogaea L.) continues to be an important task in order to facilitate quantitative trait locus (QTL) analysis and the development of tools for marker-assisted breeding. The objective of this study was to develop a comparative integrated map from two cultivated * cultivated recombinant inbred line (RIL) mapping populations and to apply in mapping Tomato spotted wilt virus (TSWV) resistance trait in peanut. A total of 4,576 simple sequence repeat (SSR) markers from three sources: published SSR markers, newly developed SSR markers from expressed sequence tags (EST) and from bacterial artificial chromosome end-sequences were used for screening polymorphisms. Two cleaved amplified polymorphic sequence markers were also included to differentiate ahFAD2A alleles and ahFAD2B alleles. A total of 324 markers were anchored on this integrated map covering 1,352.1 cM with 21 linkage groups (LGs). Combining information from duplicated loci between LGs and comparing with published diploid maps, seven homoeologous groups were defined and 17 LGs (A1-A10, B1-B4, B7, B8, and B9) were aligned to corresponding A-subgenome or B-subgenome of diploid progenitors. One reciprocal translocation was confirmed in the tetraploid-cultivated peanut genome. Several chromosomal rearrangements were observed by comparing with published cultivated peanut maps. High consistency with cultivated peanut maps derived from different populations may support this integrated map as a reliable reference map for peanut whole genome sequencing assembling. Further two major QTLs for TSWV resistance were identified for each RILs, which illustrated the application of this map. PMID- 22072101 TI - Quantitative trait loci involved in regulating seed oil composition in Arabidopsis thaliana and their evolutionary implications. AB - Fatty acid composition is an important determinant of seed oil quality. Overall, 72 QTL for 12 fatty acid traits that control seed oil composition were identified in four recombinant inbred line (RIL) populations (Ler-0 * Sha, Ler-0 * Col-4, Ler-2 * Cvi, Ler-0 * No-0) of Arabidopsis thaliana. The identified QTL explained 3.2-79.8% of the phenotypic variance; 33 of the 59 QTL identified in the Ler-0 * Sha and the Ler-0 * Col RIL populations co-located with several a priori candidate genes for seed oil composition. QTL for fatty acids 18:1, 18:2, 22:1, and fatty acids synthesized in plastids was identified in both Ler-0 * Sha and Ler-0 * Col-4 RIL populations, and QTL for 16:0 was identified in the Ler-0 * Sha and Ler-0 * No-0 RIL populations providing strong support for the importance of these QTL in determining seed oil composition. We identified melting point QTL in three RIL populations, and fatty acid QTL collocated with two of them, suggesting that the loci could be under selection for altering the melting point of seed oils to enhance adaptation and could be useful for breeding purposes. Nuclear cytoplasmic interactions and epistasis were rare. Analysis of the genetic correlations between these loci and other fatty acids indicated that these correlations would tend to strongly enhance selection for desirable fatty acids. PMID- 22072103 TI - Antihypertensive effects and mechanisms of chlorogenic acids. AB - Chlorogenic acids (CGAs) are potent antioxidants found in certain foods and drinks, most notably in coffee. In recent years, basic and clinical investigations have implied that the consumption of chlorogenic acid can have an anti-hypertension effect. Mechanistically, the metabolites of CGAs attenuate oxidative stress (reactive oxygen species), which leads to the benefit of blood pressure reduction through improved endothelial function and nitric oxide bioavailability in the arterial vasculature. This review article highlights the physiological and biochemical findings on this subject and highlights some remaining issues that merit further scientific and clinical exploration. In the framework of lifestyle modification for the management of cardiovascular risk factors, the dietary consumption of CGAs may hold promise for providing a non pharmacological approach for the prevention and treatment of high blood pressure. PMID- 22072104 TI - Enhanced expression of bone morphogenetic protein system in aldosterone-treated mouse kidneys. AB - Recent studies have shown that bone morphogenetic proteins (BMPs), particularly BMP-7, have an inhibitory role in the development of various renal diseases. We previously reported antagonistic effects of BMPs on renal mesangial cell proliferation induced by aldosterone (Aldo) in vitro. In the present study, we investigated in vivo roles of BMPs in Aldo-induced renal glomerular injury. BALB/c mice aged 6 weeks were treated with Aldo injection (5 MUg per day, intraperitoneally) and/or oral administration of high-salt (2%) water for 9 weeks. Systemic blood pressure, body weight, kidney weight and daily proteinuria were not significantly changed by Aldo and/or high-salt treatment. However, renal histological examination revealed increases in glomerular cellularity and glomerular diameter in the groups treated with Aldo injection and high-salt administration. Immunohistochemistry demonstrated expression of BMP-4 and -7 in the glomerular mesangial region. Aldo causes renal glomerular damage by stimulating mesangial cell proliferation and increasing extracellular matrix via the mineralocorticoid receptor (MR). MR messenger RNA (mRNA) expression in the renal cortex was transiently increased by 3-week treatment with Aldo and high salt intake, but was decreased by 9-week treatment. Furthermore, the expression levels of BMP-4 and -7 mRNA were enhanced in the renal cortex treated with Aldo and high-salt administration. These findings suggest that the renal BMP system is activated by Aldo under the condition of high-salt exposure, which may have a key role in antagonizing glomerular damage in vivo. PMID- 22072105 TI - Angiotensin II-induced cardiomyocyte hypertrophy in vitro is TAK1-dependent and Smad2/3-independent. AB - Cardiac hypertrophy occurs as an adaptation to hypertension but a sustained hypertrophic response can ultimately lead to heart failure. Angiotensin-II (Ang II) is released following hemodynamic overload and stimulates a cardiac hypertrophic response. AngII also increases expression of the regulatory cytokine, transforming growth factor-beta1 (TGFbeta1), which is also implicated in the cardiac hypertrophic response and can stimulate activation of Smad2/3 as well as TGFbeta-activated kinase 1 (TAK1) signaling mediators. To better understand the downstream signaling events in cardiac hypertrophy, we therefore investigated activation of Smad2/3 and TAK1 signaling pathways in response to Ang II and TGFbeta1 using primary neonatal rat cardiomyocytes to model cardiac hypertrophic responses. Small interfering RNA (siRNA) knockdown of Smad 2/3 or TAK1 protein or addition of the TGFbeta type I receptor inhibitor, SB431542, were used to investigate the role of downstream mediators of TGFbeta signaling in the hypertrophic response. Our data revealed that TGFbeta1 stimulation leads to cardiomyocyte hypertrophic phenotypes that were indistinguishable from those occurring in response to Ang II. In addition, inhibition of the TGFbeta1 type receptor abolished Ang II-induced hypertrophic changes. Furthermore, the hypertrophic response was also prevented following siRNA knockdown of TAK1 protein, but was unaffected by knockdown of Smad2/3 proteins. We conclude that Ang II-induced cardiomyocyte hypertrophy in vitro occurs in a TAK1-dependent, but Smad-independent, manner. PMID- 22072106 TI - Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity. AB - Dihydropyridine-type calcium channel blockers (CCBs) exert potent antihypertensive effects. The CCB azelnidipine decreases heart rate by suppressing sympathetic nerve activity, which affects afferent and efferent arterioles in the glomeruli. We examined whether azelnidipine can improve progressive glomerular injury in comparison with amlodipine by suppressing renal sympathetic nerve activity in Dahl salt-sensitive rats. Glomerular circulation in Dahl salt-sensitive rats was monitored with a charge-coupled device camera before and after administration of amlodipine (0.5 mg kg(-1), bolus injection) or azelnidipine (0.1 mg kg(-1), bolus injection). Systemic sympathetic nerve activity was also compared by analysis of heart rate variability with a telemetry blood pressure monitoring system after crossover administration of amlodipine (1.0 mg kg(-1) per day) and azelnidipine (3.0 mg kg(-1) per day) for 1 week. To investigate renoprotective effects, rats were treated with amlodipine (1.0 mg kg( 1) per day) or azelnidipine (3.0 mg kg(-1) per day) for 3 weeks with or without renal denervation. The efferent arteriole contracted in response to acute amlodipine but not azelnidipine treatment. The low frequency/high frequency ratio, an index of parasympathetic nerve activity, decreased in response to azelnidipine but not amlodipine treatment. In response to chronic treatment, proteinuria and glomerular injury improved to a greater extent with azelnidipine compared with amlodipine. The renoprotective effects of azelnidipine were diminished by renal denervation. Azelnidipine decreased glomerular damage in Dahl salt-sensitive rats to a greater extent than amlodipine. Azelnidipine appeared to decrease intraglomerular pressure by suppressing sympathetic nerve activity. PMID- 22072107 TI - Arterial stiffness: using simple surrogate measures to make sense of a biologically complex phenomenon. PMID- 22072108 TI - Hypothalamic gene expression in omega-3 PUFA-deficient male rats before, and following, development of hypertension. AB - Dietary deficiency of omega-3 fatty acids (omega-3 DEF) produces hypertension in later life. This study examined the effect of omega-3 DEF on blood pressure and hypothalamic gene expression in young rats, before the development of hypertension, and in older rats following the onset of hypertension. Animals were fed experimental diets that were deficient in omega-3 fatty acids, sufficient in short-chain omega-3 fatty acids or sufficient in short- and long-chain omega-3 fatty acids, from the prenatal period until 10 or 36 weeks-of-age. There was no difference in blood pressure between groups at 10 weeks-of-age; however, at 36 weeks-of-age omega-3 DEF animals were hypertensive in relation to sufficient groups. At 10 weeks, expression of angiotensin-II(1A) receptors and dopamine D(3) receptors were significantly increased in the hypothalamic tissue of omega-3 DEF animals. In contrast, at 36 weeks, alpha(2a) and beta(1) adrenergic receptor expression was significantly reduced in the omega-3 DEF group. Brain docosahexaenoic acid was significantly lower in omega-3 DEF group compared with sufficient groups. This study demonstrates that dietary omega-3 DEF causes changes both in the expression of key genes involved in central blood pressure regulation and in blood pressure. The data may indicate that hypertension resulting from omega-3 DEF is mediated by the central adrenergic system. PMID- 22072109 TI - Tetrahydrocurcumin alleviates hypertension, aortic stiffening and oxidative stress in rats with nitric oxide deficiency. AB - Tetrahydrocurcumin (THC), a major metabolite of curcumin, possesses strong antioxidant and cardioprotective properties. However, the activities of THC in hypertension and its associated complications remain unknown. The aim of this study was to investigate the effect of THC on hemodynamic status, aortic elasticity and oxidative stress in rats with N-nitro-L-arginine methyl ester (L NAME)-induced hypertension. Hypertension was induced in male Sprague-Dawley rats by administration of L-NAME (50 mg kg(-1) body weight) in drinking water for 5 weeks. THC at a dose of 50 or 100 mg kg(-1) per day was administered daily during the fourth and fifth weeks when the hypertensive state had been established. The effects of THC on hemodynamics, aortic elasticity, endothelial nitric oxide synthase (eNOS) protein expression and oxidative stress markers were assessed. Marked increases in blood pressure, peripheral vascular resistance, aortic stiffness and oxidative stress were found in rats after L-NAME administration. THC significantly reversed these deleterious effects by reducing aortic wall thickness and stiffness. These effects were associated with increased aortic eNOS expression, elevated plasma nitrate/nitrite, decreased oxidative stress with reduced superoxide production and enhanced blood glutathione. Our results provide the first evidence that THC attenuates the detrimental effect of L-NAME by improving the hemodynamic status and aortic elasticity concomitant with reduction of oxidative stress. The present study suggests that THC might be used as a dietary supplement to protect against cardiovascular alterations under nitric oxide-deficient conditions. PMID- 22072111 TI - Eosinophil count is positively correlated with coronary artery calcification. AB - Recent studies suggested that allergic disorders and increased eosinophil count were associated with atherosclerosis. The purpose of this study was to assess the relationship between eosinophil count and coronary artery calcification (CAC). We performed a cross-sectional study in 1363 consecutive participants with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAC score determined by multislice CT and peripheral eosinophil count as well as major cardiovascular risk factors, including age, body mass index, smoking status, hypertension, dyslipidemia, diabetes mellitus (DM), high-sensitivity C reactive protein and estimated glomerular filtration rate (eGFR). Sex (P=0.0004), hypertension (P=0.0002), dyslipidemia (P=0.0004) and DM (P=0.0061) were associated with log(CAC+1), respectively. Positive correlations were found between log(CAC+1), and age (r=0.325, P<0.0001) and eosinophil count (r=0.165, P<0.0001). Negative correlations were found between log(CAC+1) and eGFR (r= 0.166, P<0.0001). Multivariate linear regression analysis demonstrated that age (beta=0.314, P<0.0001), sex (beta=0.124, P<0.0001), hypertension (beta=0.084, P=0.0008), DM (beta=0.108, P<0.0001), eGFR (beta=-0.079, P=0.0021) and eosinophil count (beta=0.147, P<0.0001) were independent determinants of log(CAC+1). In conclusion, eosinophil count correlated positively with CAC in participants with clinical suspicion of CHD. PMID- 22072110 TI - Modulation of renal superoxide dismutase by telmisartan therapy in C57BL/6 Ins2(Akita) diabetic mice. AB - Renal superoxide excess, which is induced by an imbalance of the superoxide producing enzyme NAD(P)H oxidase and the superoxide-scavenging enzyme superoxide dismutase (SOD) under hyperglycemia, increases oxidative stress and contributes to the development of diabetic nephropathy. In this study, we treated non-obese and hypoinsulinemic C57BL/6-Ins2(Akita) (C57BL/6-Akita) diabetic mice with telmisartan (5 mg kg(-1) per day), an angiotensin II type 1 receptor blocker, or amlodipine (5 mg kg(-1) per day), a calcium channel blocker, for 4 weeks and compared the effects of these two anti-hypertensive drugs on renal NAD(P)H oxidase, SOD and transcription factor Nrf2 (NF-E2-related factor 2), which is known to upregulate several antioxidant enzymes including SOD. Vehicle-treated C57BL/6-Akita mice exhibited higher renal NAD(P)H oxidase and lower renal SOD activity with increased levels of renal superoxide than the C57BL/6-wild-type non diabetic mice. Interestingly, telmisartan treatment not only reduced NAD(P)H oxidase activity but also enhanced SOD activity in C57BL/6-Akita mouse kidneys, leading to a reduction of renal superoxide levels. Furthermore, telmisartan treated C57BL/6-Akita mice increased the renal protein expression of SOD and Nrf2. In parallel with the reduction of renal superoxide levels, a reduction of urinary albumin levels and a normalization of elevated glomerular filtration rate were observed in telmisartan-treated C57BL/6-Akita mice. In contrast, treatment with amlodipine failed to modulate renal NAD(P)H oxidase, SOD and Nrf2. Finally, treatment of C57BL/6-Akita mice with apocynin, an NAD(P)H oxidase inhibitor, also increased the renal protein expression of SOD and Nrf2. Collectively, our data suggest that NAD(P)H oxidase negatively regulates renal SOD, possibly by downregulation of Nrf2, and that telmisartan could upregulate renal SOD by the suppression of NAD(P)H oxidase and subsequent upregulation of Nrf2, leading to the amelioration of renal oxidative stress and diabetic renal changes. PMID- 22072112 TI - NIRF, a novel ubiquitin ligase, interacts with hepatitis B virus core protein and promotes its degradation. AB - Hepatitis B virus (HBV) core protein (HBc) is a major component of viral nucleocapsid and a multifunctional protein involved in viral maturation and release. It is unstable and present in cells at low level because of K96 lysine residue, which is a ubiquitin acceptor site. Np95/ICBP90-like RING finger protein (NIRF) has auto-ubiquitination activity which is the hallmark of a ubiquitin ligase. In the present study, ubiquitin ligase, NIRF, binds to HBc and leads to the proteasome-mediated degradation of HBc in vivo. NIRF down-regulates HBc protein level, resulting in the decrease of the amount of HBV particles in supernatant of HepG2.2.15 cells. However knockdown of NIRF significantly increases endogenous HBc protein level, leading to HBV release. The results reveal that NIRF interacts with HBc and promotes the degradation of HBc in vivo. The pathway of NIRF-mediated ubiquitin-proteasome affects the release of HBV particles by controlling the amounts of HBc. It indicates that NIRF may participate in the maturation of HBV. PMID- 22072113 TI - Preparation of encapsulated alliinase in alginate microparticles. AB - Alliinase (alkylsulphenate lyase, EC 4.4.1.4), which catalyses the production of allicin, was immobilized in alginate microparticles. Addition of pyridoxal 5' phosphate to the microparticles enhanced alliinase activity. Encapsulated alliinase were significantly higher (30 and 22%, respectively) than those of non encapsulated alliinase at 60 degrees C and at pH 2. Therefore, microencapsulation of alliinase with alginate can offer an effective way of sustaining enzyme activity during oral administration and passage through the stomach. PMID- 22072114 TI - G-CSF therapy reduces myocardial repolarization reserve in the presence of increased arteriogenesis, angiogenesis and connexin 43 expression in an experimental model of pacing-induced heart failure. AB - G-CSF (granulocyte colony-stimulating factor) treatment has been shown to cause beneficial effects including a reduction of inducible arrhythmias in rodent models of ischemic cardiomyopathy. The aim of the present study was to test whether these effects do also apply to pacing-induced non-ischemic heart failure. In 24 female rabbits, heart failure was induced by rapid ventricular pacing. 24 rabbits were sham operated. The paced rabbits developed a significant decrease of ejection fraction. 11 heart failure rabbits (CHF) and 11 sham-operated (S) rabbits served as controls, whereas 13 sham (S-G-CSF) and 13 heart failure rabbits (CHF-G-CSF) were treated with 10 MUg/kg G-CSF s.c. over 17 +/- 4 days. G CSF treatment caused a ~25% increased arterial and capillary density and a ~60% increased connexin 43 expression in failing hearts. In isolated, Langendorff perfused rabbit hearts eight monophasic action potential recordings showed prolongation of repolarization in CHF as compared with controls in the presence of the QT prolonging agent erythromycin (+33 +/- 12 ms; p < 0.01). Moreover, a significant increase in dispersion of repolarization contributed to a significantly higher rate of ventricular tachyarrhythmias in CHF. G-CSF-pre treated hearts showed a further increase in prolongation of repolarization as compared with S and CHF. The further increase in dispersion of repolarization [S G-CSF: +23 +/- 9 ms (spatial), +13 +/- 7 ms (temporal); CHF-G-CSF: +38 +/- 14 ms (spatial), +10 +/- 4 ms (temporal); p < 0.05 as compared with S and CHF], increased the incidence of ventricular tachyarrhythmias. In summary, chronic G CSF treatment has moderate beneficial effects on parameters potentially related to hemodynamic function in the non-ischemic rabbit CHF model. However, a significant reduction of repolarization reserve might seriously challenge its suitability as a therapeutic agent for chronic CHF therapy. PMID- 22072115 TI - Second generation automated anti-CCP test better predicts the clinical diagnosis of rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases. The presence of antibodies to cyclic citrullinated peptide (CCP) is better at discriminating RA patients and is also associated with significantly more disease activity compared to serum rheumatoid factor. In this study, we assessed two new automated second generation tests to detect the presence of anti-CCP antibodies in 226 serum samples submitted to the Clinical Immunology Laboratory for anti-CCP antibody testing. We compared CCP antibody results on these samples obtained using the ImmunoCAP 250 (Phadia) and the Architect i2000SR (Abbott Laboratories) instruments to our currently used CCP IgG third generation manual ELISA (Inova Diagnostics). One hundred and fifty-four samples were negative while 52 were positive by all three tests. Eighteen samples were negative by the automated tests but weakly/moderately positive by manual ELISA yielding an overall concordance of 79%. When we compared the discordant test results to patient diagnosis, we observed a better correlation with clinical RA diagnosis for the new automated tests compared to the manual ELISA. These two new anti-CCP antibody tests have the benefit of automation and may have better positive predictive value for the diagnosis of RA than our current manual ELISA. PMID- 22072116 TI - Difference in survival and prognostic factors between smokers and never-smokers with advanced non-small-cell lung cancer. AB - BACKGROUND: Our aims were to investigate whether the association between smoking and survival is significant when adjusted for prognostic factors including use of epidermal growth factor tyrosine kinase inhibitors and the Glasgow Prognostic Score, an established score for inflammation, and to explore prognostic factors. METHODS: We analyzed 244 patients with stage IIIB or IV non-small-cell lung cancer in a registry, including only chemotherapy-receiving outpatients with performance status zero. RESULTS: Of 244 patients, 170 had died and the median follow-up time for the 74 surviving patients was 12.0 months. In multivariate Cox regression, smoker (hazard ratio compared to never-smoker: 1.67, P < 0.01), stage IV (hazard ratio compared to IIIB: 1.72, P < 0.01), and elevated C-reactive protein level (hazard ratio per 1 mg/dL increase: 1.08, P < 0.01) were significantly associated with shorter survival. The association between survival and smoking was significant, even after adjustment for the Glasgow Prognostic Score and regimens of chemotherapy (hazard ratio: 1.72, P = 0.02). In never smokers, increased neutrophils were a major determinant of shorter survival and the interaction test between smoking and neutrophils was significant (hazard ratio per 1,000/mm(3) increase for smokers: 1.01; hazard ratio per 1,000/mm(3) increase for never-smokers: 1.44, P for interaction <0.01). CONCLUSIONS: Known factors including treatment response or inflammatory process are not responsible for the fact that advanced non-small-cell lung cancer patients without any history of smoking have better survival than those who have smoked. PMID- 22072117 TI - Cylindrospermopsis raciborskii exudate-Cu complexes: impact on copper dynamics and bioavailability in an aquatic food chain. AB - INTRODUCTION: The increasing contamination of aquatic environments motivates studies on the interactions among natural dissolved organic matter, metals, and the biota. This investigation focused on the organic exudates of the toxic cyanobacteria Cylindrospermopsis raciborskii as a Cu carrier through a three level aquatic trophic chain (bacteria, protozoa, and copepod). DISCUSSION: The effects of bacteria activity and growth on the metal-organic complexes were evaluated through changes in free Cu(2+) ions, total dissolved, and total particulate Cu. To be sure that the added copper would be complexed to the exudates, its complexing properties were previously determined. The cyanobacteria exudate-Cu complexes were furnished to bacteria that were further used as a food source to the protozoan Paramercium caudatum. This was then furnished as food to the copepod Mesocyclops sp. The results showed that, in general, the cyanobacterial exudates decreased Cu bioavailability and toxicity to the first trophic level (bacteria), but because the heterotrophic bacteria accumulated Cu, they were responsible for the transference for the otherwise low availability metal form. Both the bacteria and protozoan organisms accumulated Cu, but no metal accumulation was detected in the copepods. PMID- 22072118 TI - Highly efficient degradation of ofloxacin by UV/Oxone/Co2+ oxidation process. AB - INTRODUCTION: In this study, UV/Oxone/Co(2+) oxidation process was applied to degradation of ofloxacin (OFL) in the presence of Co(2+) as the catalytic and Oxone as the oxidant. The operation parameters including pH, temperature, dosages of reagents, and reaction time were studied in detail. RESULTS: The results showed that the optimum conditions for the UV/Oxone/Co(2+) processes were determined as follows: temperature = 25 degrees C, pH = 5.0, [Oxone] = 0.6 mmol/L, [Oxone]/[Co(2+)] = 1,000, and reaction time = 60 min. Under these conditions, 100% of the OFL degraded. The kinetics was also studied, and degradation of OFL by the UV/Oxone/Co(2+) process could be described by first order kinetics. CONCLUSIONS: Mineralization of the process was investigated by measuring the total organic carbon (TOC), and the TOC decreased by 87.0% after 60 min. This process could be used as a pretreatment method for wastewater containing ofloxacin. PMID- 22072119 TI - CIP2A expression is elevated in cervical cancer. AB - Early detection of cervical cancer is critical for a favorable prognosis. Standard cytological detection methods, such as Pap smear, are highly subjective and HPV detection is not a reliable marker for predicting the malignancy potential of cervical lesions. As a result, there is a demand for a diagnostic assay capable of sensitive and specific detection of cervical cancer. In this preclinical exploratory study, qRT-PCR and western blotting were used to assess expression levels of CIP2A and p16INK4a in cervical tissue samples (n(normal adjacent) = 23, n(tumor) = 29). CIP2A was abundantly expressed in cervical cancer cell lines and was not expressed in normal epithelial cells. CIP2A mRNA levels were higher in cervical tumor tissues in comparison to the level of CIP2A mRNA in normal adjacent tissue from cervical cancer patients. CIP2A protein was specifically expressed in cervical tumor tissues at different cancer grades and stages, and was not observed in normal adjacent tissue. Elevated CIP2A mRNA levels in cervical tissues had a sensitivity of 80% and specificity of 91% and CIP2A protein expression detection had a sensitivity of 83% and specificity of 100%, similar to that of p16INK4a, with no correlation of CIP2A expression with HPV infection, age, race, or other patient characteristics. However the number of samples analyzed in this preliminary study is limited and a large prospective cohort study is necessary to further evaluate CIP2A as a biomarker for cervical cancer. PMID- 22072120 TI - Potential hydrophobic protein markers of breast cancer in Malaysian Chinese, Malay and Indian patients. AB - Breast cancer is a leading cause of worldwide mortality in females. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of these, the Chinese had the most number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was used to identify protein profile changes in cancerous tissues compared with the normal tissues, the tissues were collected from patients of three different ethnicities, i.e. Chinese, Malay and Indian. Ten differentially expressed hydrophobic proteins were identified. We had evaluated the potential of these proteins as biomarker for infiltrating ducal carcinoma (IDC) and the ethnic-specific expression of these proteins was also determined. The data showed that peroxiredoxin-2, heat shock protein 60, protein disulfide isomerase and calreticulin may serve as ethnic-related potential markers for either one or combination of Chinese, Malay and Indian cohorts as their expression levels were significantly high in the cancerous tissues compared to the normal tissues in the ethnic group tested. PMID- 22072121 TI - KRAS mutation detection in Tunisian sporadic coloractal cancer patients with direct sequencing, high resolution melting and denaturating high performance liquid chromatography. AB - The Kirsten Rat Sarcoma (KRAS) oncogene has been introduced recently as a genetic biomarker for metastatic sporadic colorectal cancer prior to anti-EGFR treatment. Identifying patients with KRAS mutations that not respond to EGFR targeted therapies require sensitive, rapid and efficacious routine technique. We have attempted to evaluate the efficiency of three conventional methods: direct sequencing, HRM and DHPLC, to detect mutations in codon 12 and 13 of the KRAS exon2 gene. For this first Tunisian study on KRAS, we detected 45.83% of altered KRAS gene among 48 formalin-fixed paraffin-embedded sporadic colorectal adenocarcinoma patients. The use of HRM-sequencing allowed as enlarging the detected KRAS exon 2 mutations (22/48) in comparison with direct sequencing (17/48). DHPLC was used to confirm results when consensus was not observed between HRM and direct sequencing. This study brings an interesting data concerning an inter-method validation between sequencing and HRM in the investigation of sporadic colorectal cancer biomarker. It also shows that KRAS mutations occur at similar frequencies in Tunisian patients as in other populations; and suggests that the same genes are at play in sporadic CRC cancer, despite ethnic, geographical and environmental differences between countries. PMID- 22072122 TI - Nuclear co-expression of p14ARF and p16INK4A in uterine cervical cancer-derived cell lines containing HPV. AB - The Papanicolaou test (Pap) has been responsible for a significant reduction of cervical cancer-related morbimortality. In order to increase its sensitivity and specificity new markers have been studied and incorporated to cytological and histological methods for diagnosis for cervical cancer, such as p16INK4A that has been considered the immunocytochemical marker of choice for detection of HPV related cancers. We considered that p14ARF could be a complementary marker in order to improve the accuracy of cytological diagnosis because its genetic proximity to p16INK4A. We performed a systematic analysis of several putative cervical cancer markers in order to evaluate their performance in the detection of malignancy, in comparison with p16INK4A and p14ARF, using immunocytochemistry (ICC), immunofluorescence (IF) and Western blot analyses. Most markers were non specific and could not discriminate HPV infected cancer cell lines from other non HPV malignant. In contrast, nuclear co-expression of p16INK4A and p14ARF was observed only in HPV-transformed cancer cell lines. Notably, in C-33A cervical cancer cells (HPV negative), p14ARF was present in the nucleoli, but p16INK4A was conspicuously absent from the nuclei of these cells. We conclude that both markers; p16INK4A and p14ARF are complementary and should be evaluated jointly in order to improve the accuracy of cytological diagnosis of cervical cancer. PMID- 22072123 TI - Polymorphism in cytochrome P450 1A2 and their interaction with risk factors in determining risk of squamous cell lung carcinoma in men. AB - The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma. PMID- 22072125 TI - Urban women's preferences for learning of their mammogram result: a qualitative study. AB - Research suggests that communication of mammogram results is flawed for many low income ethnic minority women. This study conducted four focus groups with low income inner-city minority women (n = 34). The goals of our project were: (1) to elucidate women's experiences learning of their result; (2) to elicit their preferences as to how this communication could be improved; and (3) to gather information to help inform the development of a new tool for communicating mammogram results. Salient themes included dissatisfaction with result communication; difficulty elucidating the meaning of a typical results notification letter; a preference for direct verbal communication of results and for print materials that included pictures, testimonials, and an action plan including a hotline to call with questions; and a strong interest in advance education about the likelihood of having to return for additional follow up. Video and other programs to inform patients before the test about what happens after may improve patient satisfaction and enhance women's understanding of their personal result and follow up plan. PMID- 22072124 TI - Growth of ammonia-oxidizing archaea and bacteria in cattle manure compost under various temperatures and ammonia concentrations. AB - A recent study showed that ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) coexist in the process of cattle manure composting. To investigate their physiological characteristics, liquid cultures seeded with fermenting cattle manure compost were incubated at various temperatures (37 degrees C, 46 degrees C, or 60 degrees C) and ammonium concentrations (0.5, 1, 4, or 10 mM NH (4) (+) -N). The growth rates of the AOB and AOA were monitored using real-time polymerase chain reaction analysis targeting the bacterial and archaeal ammonia monooxygenase subunit A genes. AOB grew at 37 degrees C and 4 or 10 mM NH (4) (+) -N, whereas AOA grew at 46 degrees C and 10 mM NH (4) (+) -N. Incubation with allylthiourea indicated that the AOB and AOA grew by oxidizing ammonia. Denaturing gradient gel electrophoresis and subsequent sequencing analyses revealed that a bacterium related to Nitrosomonas halophila and an archaeon related to Candidatus Nitrososphaera gargensis were the predominant AOB and AOA, respectively, in the seed compost and in cultures after incubation. This is the first report to demonstrate that the predominant AOA in cattle manure compost can grow and can probably oxidize ammonia under moderately thermophilic conditions. PMID- 22072126 TI - A pilot program in collaboration with African American churches successfully increases awareness of the importance of cancer research and participation in cancer translational research studies among African Americans. AB - African Americans are underrepresented in cancer research. We evaluate whether collaboration with African American churches can improve cancer awareness and increase participation in translational research protocols among African Americans. From February to April 2010, the Mayo Clinic partnered with African American Jacksonville churches to provide educational programs focused on cancer research and healthy behaviors. Education on multiple myeloma and on-site access to a translational cancer research pilot project evaluating the prevalence of monoclonal gammopathies and t(14,18) in African Americans was offered. Seventy four percent, 236 out of 318 participants, returned the questionnaires. The majority of participants had never received information on multiple myeloma (67%), had never received clinical research study information (57%), and were enrolled in the translational research studies (55%). Partnerships with African American churches in community education projects that bring research to church venues are effective in improving cancer awareness and in increasing research participation among African Americans. PMID- 22072127 TI - Direct lateral approach to pathology at the craniocervical junction: a technical note. AB - BACKGROUND: Approaches to the foramen magnum and upper cervical spine traditionally include the posterior midline, far lateral, and endoscopic endonasal approaches. The far lateral approach is a well-established technique for the removal of pathology ventrolateral to the brainstem and the craniocervical junction, but it may be too extensive for lesions limited to areas far from the midline. OBJECTIVE: To present an alternative to the commonly used approaches to the foramen magnum and upper cervical. METHODS: We used an approach directly overlying ventral or lateral pathology. RESULTS: Two cases are presented in which the direct lateral approach followed by an occipitocervical fusion was successfully performed. CONCLUSION: This approach can be considered for patients in whom a ventral decompression is necessary but an endoscopic endonasal approach is undesirable or when a ventral, lateral, and ventrolateral resection of tumor, pannus, or infection is required. PMID- 22072128 TI - Transcortical venous approach for direct embolization of a cavernous sinus dural arteriovenous fistula: technical case report. AB - BACKGROUND AND IMPORTANCE: Dural arteriovenous fistulas (dAVFs) represent 10% to 15% of all intracranial arteriovenous malformations. Most often, embolization is accomplished with transfemoral catheter techniques. We present a case in which embolization of a cavernous sinus dAVF was made possible through transcranial cannulation of a cortical draining vein. CLINICAL PRESENTATION: An 82-year-old woman presented with diplopia, left sixth cranial nerve palsy, intraocular hypertension, and bilateral chemosis. Angiography revealed a complex cavernous dAVF with cortical venous reflux, supplied by both external carotid arteries and the left meningohypophyseal trunk. Percutaneous transvenous access failed, and only partial occlusion was achieved by transarterial embolization. A frontotemporal craniotomy was performed to access the superficial middle cerebral vein in the left sylvian fissure. Under fluoroscopic guidance, a microcatheter was advanced through this vein to the floor of the middle cranial fossa and into the dAVF, permitting coil occlusion. CONCLUSION: This transcranial vein technique may be a useful adjunct in dAVF therapy when percutaneous transarterial or transvenous approaches fail or are not possible. PMID- 22072129 TI - Image-guided transcranial Doppler ultrasound. PMID- 22072130 TI - Treatment of Harlequin syndrome. PMID- 22072131 TI - Cerebral compromise and multimodality monitoring after SAH. PMID- 22072132 TI - Manucher Javid, urea, and the rise of osmotic therapy for intracranial pressure. AB - Therapy with hypertonic solutions is one of the mainstays of neurosurgical treatment for all types of neurological injury. Although the initial research with hypertonic agents in the early decades of the 20th century showed great promise for these agents to lower intracranial pressure, this research also showed a considerable rate of adverse effects and complications. By the 1940s and 1950s, hypertonic therapy had been discounted as unsafe and was rarely used in neurosurgery. In the late 1950s, Manucher J. Javid and Paul Settlage at the University of Wisconsin began experimenting with infusions of urea as an agent to control intracranial pressure. Their experiments were wildly successful, and urea became a drug of major importance to neurosurgeons worldwide in only a few years. This article chronicles the work of Javid and Settlage, including a discussion of the early research on hypertonic agents, the initial difficulty the Wisconsin researchers had in disseminating their results, the widespread acceptance that followed, and the impact that these discoveries had on the neurosurgical community. The prominent place that hypertonic agents now hold in the armamentarium of neurosurgeons is owed to the work of Dr Javid, as illustrated in this historical analysis. PMID- 22072133 TI - Achille Louis Foville's atlas of brain anatomy and the Defoville syndrome. AB - Achille Louis Foville's atlas of brain anatomy (1844) is one of the most artistic and detailed works on neuroanatomy in the medical literature. The outstanding drawings by the 2 artists, Emile Beau and Frederic-Michel Bion, highlight all the philosophy, ability, and sensibility of A.L. Foville in carefully dissecting the superficial and deep structures of the brain and spinal cord. Several plates show true brain fiber dissections of high artistic and academic value. As a result of an early misrecognition in the medical literature, "inferior Foville syndrome" has been wrongly attributed to Achille Louis Foville rather than his son, Achille Louis Francois Foville (1832-1887), also called Defoville. Therefore, we suggest that Defoville, who actually described the pontine syndrome for the first time in the neurological literature, deserves to be credited for this syndrome and that the syndrome should be called the Defoville syndrome. Through analyzing the political and scientific events in France in the 19th century, we highlight the invaluable contributions of A.L. Foville and his son to the history of neuroanatomy and neurology. PMID- 22072134 TI - Improvement of secondary fixed dystonia of the upper limb after chronic extradural motor cortex stimulation in 10 patients: first reported series. AB - BACKGROUND: Fixed dystonic postures secondary to ischemic, traumatic, or postsurgical lesions located in the basal ganglia and brainstem constitute a major therapeutic challenge and limit motor rehabilitation efficacy. They are often refractory to conservative treatment. Aberrant cerebral plasticity developed after deep brain lesions is thought to lead to abnormal cortical representation of the affected part of the body and then to pathological fixed postures. OBJECTIVE: To assess the efficacy of motor cortex stimulation in patients with upper limb fixed dystonia. METHODS: Ten patients were submitted to computer-assisted and electromyography-monitored implantation of intracranial epidural electrodes over the central cortical sulcus contralateral to the affected limb. Patients were followed up from 1 to 9 years (9 patients), except for patient 10, whose follow-up was limited to 4 months. RESULTS: Seven of 7 patients showed > 30% improvement in the Disability of Shoulder, Arm, and Hand Scale and an overall 70% increase in the score of the Short Form-36 Physical Activity subscale with significant and stable improvement of quality of life during stimulation. The partial recovery of hand dexterity observed in most of the treated patients additionally contributed to a significant improvement of their quality of life. CONCLUSION: Although the pathophysiology of fixed dystonia is unknown, our results suggest a major role of the motor cortex in this condition and reinforce the hypothesis that postlesional delayed cortical rearrangements might take place in these forms and be the target of effective therapeutic neuromodulation. PMID- 22072135 TI - Partial ipsilateral C7 transfer to the upper trunk for C5-C6 avulsion of the brachial plexus. AB - BACKGROUND: Ipsilateral whole C7 root transfer has been reported in treating C5 C6 avulsion. To minimize donor deficits, partial ipsilateral C7 (PIC7) transfer was developed. OBJECTIVE: To investigate the long-term results of PIC7 transfer to the upper trunk in treating C5-C6 avulsion of the brachial plexus. METHODS: We prospectively studied 8 young adults with C5-C6 avulsion. Five patients (group A) who also had spinal accessory nerve (SAN) injury underwent PIC7 transfer to the upper trunk. The other 3 patients (group B) without SAN injury underwent a combination of PIC7 to the upper trunk and the SAN to the suprascapular nerve (SSN). Postsurgical evaluations including donor deficits, functional recovery, and co-contraction of the muscles were performed 1 week later and then at intervals of 3 months. RESULTS: After a mean period of 39.2 months, all subjects were found to have gained elbow flexion of 110 to 150 degrees with muscle strength of M4-5. The patients in group B achieved external rotation of 60 to 70 degrees at M3-4, and 2 achieved shoulder abductions approaching 180 degrees at M4. The patients in group A showed no active external rotation and shoulder abduction of 25 to 50 degrees at M2-3. The temporary deficits caused by PIC7 transfer disappeared in all subjects within the first 3 months. Co-contraction of the latissimus dorsi against the deltoid was recorded in group A but not in group B. CONCLUSION: PIC7 transfer, when combined with SAN transfer to SSN as a novel approach, is a safe, easy, and efficacious surgical procedure for patients with simple C5-C6 avulsion. PMID- 22072136 TI - Neisseria meningitidis induces platelet inhibition and increases vascular endothelial permeability via nitric oxide regulated pathways. AB - Despite antibiotic therapy, infections with Neisseria meningitidis still demonstrate a high rate of morbidity and mortality even in developed countries. The fulminant septicaemic course, named Waterhouse-Friderichsen syndrome, with massive haemorrhage into the adrenal glands and widespread petechial bleeding suggest pathophysiological inhibition of platelet function. Our data show that N. meningitidis produces the important physiological platelet inhibitor and cardiovascular signalling molecule nitric oxide (NO), also known as endothelium derived relaxing factor (EDRF). N. meningitidis -derived NO inhibited ADP induced platelet aggregation through the activation of soluble guanylyl cyclase (sGC) followed by an increase in platelet cyclic nucleotide levels and subsequent activation of platelet cGMP- and cAMP- dependent protein kinases (PKG and PKA). Furthermore, direct measurement of horseradish peroxidase (HRP) passage through a vascular endothelial cell monolayer revealed that N. meningitidis significantly increased endothelial monolayer permeability. Immunfluorescence analysis demonstrated NO dependent disturbances in the structure of endothelial adherens junctions after co-incubation with N. meningitidis . In contrast to platelet inhibition, the NO effects on HBMEC were not mediated by cyclic nucleotides. Our study provides evidence that NO plays an essential role in the pathophysiology of septicaemic meningococcal infection. PMID- 22072137 TI - Urban health educators' perspectives and practices regarding school nutrition education policies. AB - Although nutrition-related health education policies exist at national, state and local levels, the degree to which those policies affect the everyday practices of health education teachers who are charged with executing them in schools is often unclear. The purpose of this study was to examine the nutrition-related health education policy matrix that affected one urban school district, the health education teachers' awareness of those policies, the impact of nutrition policies on teachers' instruction and challenges teachers perceived in executing comprehensive nutrition education. The study used interpretive ethnography to examine the educational contexts and perspectives of 27 health educators from 24 middle schools in one urban district in the Midwestern United States. Data were collected through school observations, interviews with key personnel and document collection. We found that a network of nutrition-related education policies governed health education teachers' instruction, but that teachers were uniformly unaware of those policies. Without institutional coherence and clear directives, health education teachers taught little nutrition content, primarily due to poor training, professional development, instructional resources and administrative accountability. The results are discussed in light of the enormous challenges in many urban schools and the need for nutrition education professional development. PMID- 22072138 TI - Optimization of culture conditions for 1,3-propanediol production from glycerol using a mutant strain of Klebsiella pneumoniae. AB - In the present work, mutant strains of Klebsiella pneumoniae with deletions of the als gene encoding acetolactate synthase involved in synthesis of 2,3 butanediol, the ldhA gene encoding lactate dehydrogenase required for lactate synthesis, or both genes, were prepared. Production of 1,3-propanediol (1,3-PD) from glycerol was enhanced in the ldhA mutant strain (DeltaldhA), but lower in Deltaals or Deltaals DeltaldhA mutant strains compared to the parent strain, concomitant with a reduction in the glycerol consumption rate, indicating that deletion of ldhA alone was useful to improve 1,3-PD production. Fed-batch fermentation analysis revealed that, in the DeltaldhA mutant strain, 1,3-PD production was higher at low pH than at neutral pH; the reverse was true for the parent strain. Further optimization of culture conditions, by variation of aeration and glycerol feed rates, dramatically improved the production of 1,3-PD by the mutant strain. The maximum level attained was 102.7 g l(-1) of 1,3-PD from glycerol. PMID- 22072139 TI - Characterization and enhanced production of prodigiosin from the spoiled coconut. AB - Many bacterial secondary products are bioactive substances that play an important role in biotechnology and pharmacology (e.g., as antibiotics or antitumor agents). Over the past few years interest in prodigiosin has been increased due to its promising anti-cancer activity. Prodigiosin is also of potential clinical interest because it is reported to have anti-fungal, anti-bacterial, anti protozoal/anti-malarial, and immunosuppressive activity. Thus there is a need to develop a high-throughput and cost-effective bioprocess for the production of prodigiosin. In the present study, Serratia rubidaea was isolated from colored portion of a spoiled coconut and further it was authenticated by MTCC, India. The various parameters like temperature, pH, salt concentration, and precursors were optimized for the production of prodigiosin. We now report that the pigment production was higher in our isolated strain than S. marcescens. It was observed that prodigiosin binds with plastic, paper, and fibers and thus in near future, it can also be used as a natural dye. PMID- 22072140 TI - In silico characterization of alkaline proteases from different species of Aspergillus. AB - A total of 49 protein sequences of alkaline proteases retrieved from GenBank representing different species of Aspergillus have been characterized for various physiochemical properties, homology search, multiple sequence alignment, motif, and super family search and phylogenetic tree construction. The sequence level homology was obtained among different groups of alkaline protease enzymes, viz alkaline serine protease, oryzin, calpain-like protease, serine protease, subtilisin-like alkaline proteases. Multiple sequence alignment of alkaline protease protein sequence of different Aspergillus species revealed a stretch of conserved region for amino acid residues from 69 to 110 and 130-204. The phylogenetic tree constructed indicated several Aspergillus species-specific clusters for alkaline proteases namely Aspergillus fumigatus, Aspergillus niger, Aspergillus oryzae, Aspergillus clavatus. The distributions of ten commonly observed motifs were analyzed among these proteases. Motif 1 with a signature amino acid sequence of 50 amino acids, i.e., ASFSNYGKVVDIFAPGQDILSCWIGSTTATNTISGTSMATPHIVGLSCYL, was uniformly observed in proteases protein sequences indicating its involvement with the structure and enzymatic function. Motif analysis of acidic proteases of Aspergillus and bacterial alkaline proteases has revealed different signature amino acid sequences. The superfamily search for these proteases revealed the presence of subtilases, serine-carboxyl proteinase, calpain large subunit, and thermolysin like superfamilies with 45 representing the subtilases superfamily. PMID- 22072141 TI - Xylanase and beta-xylosidase production by Aspergillus ochraceus: new perspectives for the application of wheat straw autohydrolysis liquor. AB - The xylanase biosynthesis is induced by its substrate-xylan. The high xylan content in some wastes such as wheat residues (wheat bran and wheat straw) makes them accessible and cheap sources of inducers to be mainly applied in great volumes of fermentation, such as those of industrial bioreactors. Thus, in this work, the main proposal was incorporated in the nutrient medium wheat straw particles decomposed to soluble compounds (liquor) through treatment of lignocellulosic materials in autohydrolysis process, as a strategy to increase and undervalue xylanase production by Aspergillus ochraceus. The wheat straw autohydrolysis liquor produced in several conditions was used as a sole carbon source or with wheat bran. The best conditions for xylanase and beta-xylosidase production were observed when A. ochraceus was cultivated with 1% wheat bran added of 10% wheat straw liquor (produced after 15 min of hydrothermal treatment) as carbon source. This substrate was more favorable when compared with xylan, wheat bran, and wheat straw autohydrolysis liquor used separately. The application of this substrate mixture in a stirred tank bioreactor indicated the possibility of scaling up the process to commercial production. PMID- 22072142 TI - Isolation and characterization of a novel plasma membrane intrinsic protein gene, LcPIP1, in Leymus chinensis that enhances salt stress tolerance in Saccharomyces cerevisiae. AB - A novel plasma membrane intrinsic, LcPIP1, was isolated from Leymus chinensis using RACE method. The LcPIP1 has 288 amino acids with an estimated molecular mass of 30.6 kDa. Semi RT-PCR analysis indicated that the expression level of LcPIP1 was obviously higher in leaf than root. The LcPIP1 was also found to be induced by salt stress. In addition, transformed with the LcPIP1, Saccharomyces cerevisiae could increase tolerance to salt stress. These results indicate that the LcPIP1 gene seems to play a role in resistance against salt stress. PMID- 22072143 TI - Overview of fungal lipase: a review. AB - Lipases (triacylglycerolacyl hydrolases, EC3.1.1.3) are class of enzymes which catalyze the hydrolysis of long-chain triglycerides. In this review paper, an overview regarding the fungal lipase production, purification, and application is discussed. The review describes various industrial applications of lipase in pulp and paper, food, detergent, and textile industries. Some important lipase producing fungal genera include Aspergillus, Penicillium, Rhizopus, Candida, etc. Current fermentation process techniques such as batch, fed-batch, and continuous mode of lipase production in submerged and solid-state fermentations are discussed in details. The purification of lipase by hydrophobic interaction chromatography is also discussed. The development of mathematical models applied to lipase production is discussed with special emphasis on lipase engineering. PMID- 22072144 TI - Composition and source apportionment of PAHs in sediments at river mouths and channel in Kaohsiung Harbor, Taiwan. AB - Fifty-eight sediment samples were collected in 2009 from the bottom of river mouths near Kaohsiung Harbor (Taiwan) and the harbor channel for the analyses of polycyclic aromatic hydrocarbons (PAHs) using gas chromatography-mass spectrometry (GC-MS). Concentrations of total PAHs varied from 39 to 30,521 ng g( 1) (dry weight); samples collected from the mouths of Love River, Canon River, Jen-Gen River, and Salt River showed the highest PAHs concentrations. This indicates that the major sources of sediment PAHs come from those polluted urban rivers and the harbor channel. In samples collected from the Salt River mouth, approximately 43% of the PAHs are identified as PAHs with 2 or 3 rings. However, samples collected from other locations contain predominantly PAHs with 4 rings (32 to 42%) or 5 and 6 rings (36 to 44%). Emissions from traffic-related sources and waste incineration contribute to the majority of PAHs found in most channel and river mouth sediments. However, coal/oil combustion is the main cause of high concentrations of PAHs observed in the Salt River mouth sediments. Principal component analyses with multivariate linear regression (PCA/MLR) have been used to further quantify the source contributions, and the results show that the contributions of coal/oil combustion, traffic-related and waste incineration are 37%, 33% and 30%, respectively. PMID- 22072145 TI - Matrix metalloproteinase-2 polymorphisms and clinical outcome of Chinese patients with nonsmall cell lung cancer treated with first-line, platinum-based chemotherapy. AB - BACKGROUND: Matrix metalloproteinase-2 (MMP-2) is well known for its critical role in cell survival and cancer development. It also plays an important role in hematopoietic recovery after chemotherapy-induced myelosuppression. In this study, the authors investigated the association of MMP-2 polymorphisms with treatment efficacy and the occurrence of severe toxicity in patients with nonsmall cell lung cancer (NSCLC) who were receiving first-line, platinum-based chemotherapy. METHODS: A pharmacogenetic association study was performed in 663 Chinese patients who had inoperable stage III/IV NSCLC and were receiving first line, platinum-based regimens. Information about objective response, progression free survival, overall survival, grade 3 or 4 gastrointestinal toxicity (nausea/vomiting), and hematologic toxicity (neutropenia, anemia, thrombocytopenia) was available. Sixteen tag single nucleotide polymorphisms (SNPs) of MMP-2 were assessed. RESULTS: In 7 polymorphisms, significant associations were observed with the incidence of grade 3 or 4 neutropenia. The variant homozygotes of reference SNP rs12934241 exhibited the most significant effect on the risk of neutropenia, leading to an incidence rate that increased from 12.3% (for the C/C genotype) to 50% (for the T/T genotype; odds ratio, 8.33; P = 8.8 * 10(-5)). Stratified analyses indicated that rs12934241 exhibited a much stronger influence in the cisplatin-gemcitabine regimen subgroup than subgroups that received other regimens (P(interaction) = .003). Further haplotype analyses produced results that were consistent with results from single-SNP analyses. However, no significant association was observed between MMP-2 polymorphisms and treatment efficacy, including response rate, clinical benefit, progression-free survival, and overall survival. CONCLUSIONS: To the authors' knowledge, this study provides the first evidence for a predictive role of MMP-2 polymorphisms in the variability of severe chemotherapy-related neutropenia among Chinese patients with platinum-treated, advanced NSCLC. PMID- 22072146 TI - Side-to-side isoperistaltic strictureplasty for chronic ischemic enteritis: report of a case. AB - Chronic ischemic enteritis can cause intestinal strictures, but extensive resection of the small intestine may leave patients with short bowel syndrome. Thus, the importance of preserving diseased small bowel is now recognized. We report a case of successful side-to-side isoperistaltic strictureplasty (SSIS), performed to prevent short bowel syndrome, in a patient with ischemic enteritis caused by strangulated intestinal obstruction. SSIS is useful for preserving the intestinal absorptive function in patients with a long narrowed bowel loop caused by ischemic change. To our knowledge, this is the first report of the successful treatment of a long stricture resulting from ischemic enteritis, achieved by performing SSIS. PMID- 22072147 TI - Total resection of the right hepatic vein drainage area with the aid of three dimensional computed tomography. AB - PURPOSE: We analyzed the feasibility and safety of our preliminary surgical approach for total hepatic resection of the right hepatic vein drainage area (THR RHV) with the aid of three-dimensional computed tomography (3D-CT) guidance. METHODS: Clinical findings and 3D-CT volumetry results were investigated in five patients who underwent THR-RHV for a hepatic malignant tumor close to the right hepatic vein (RHV). RESULTS: The mean estimated remnant liver volume after a conventional right lobectomy was 474 ml, whereas that after THR-RHV was 614 ml, indicating that 140 ml (13.8%) of additional liver volume had been preserved by performing THR-RHV. The median operative time, mean ischemic time, and mean blood loss during surgery were 406 min, 51 min, and 587 ml, respectively. Histological examinations confirmed a negative surgical margin in all five patients. The mean liver volume estimated by 3D-CT was 458 ml, whereas the mean actual resected liver volume was 468 g, resulting in a mean error ratio of 3.1%. CONCLUSIONS: THR RHV allowed for a higher remnant liver volume than that after conventional right lobectomy of the liver, and proved feasible with acceptable perioperative results. This technique thus promotes both safety and curability for patients with a tumor close to the RHV. PMID- 22072148 TI - Prognostic significance of glucose transporter-1 (GLUT1) gene expression in rectal cancer after preoperative chemoradiotherapy. AB - PURPOSE: Most cancer cells exhibit increased glycolysis. The elevated glucose transporter 1 (GLUT1) expression has been reported to be associated with resistance to therapeutic agents and a poor prognosis. We wondered whether GLUT1 expression was associated with the clinical outcome in rectal cancer after preoperative chemoradiotherapy (CRT), and whether glycolysis inhibition could represent a novel anticancer treatment. METHODS: We obtained total RNA from residual cancer cells using microdissection from a total of 52 rectal cancer specimens from patients who underwent preoperative CRT. We performed transcriptional analyzes, and studied the association of the GLUT1 gene expression levels with the clinical outcomes. In addition, we examined each proliferative response of three selected colorectal cancer cell lines to a glycolysis inhibitor, 3-bromopyruvic acid (3-BrPA), with regard to their expression of the GLUT1 gene. RESULTS: An elevated GLUT1 gene expression was associated with a high postoperative stage, the presence of lymph node metastasis, and distant recurrence. Moreover, elevated GLUT1 gene expression independently predicted both the recurrence-free and overall survival. In the in vitro studies, we observed that 3-BrPA significantly suppressed the proliferation of colon cancer cells with high GLUT1 gene expression, compared with those with low expression. CONCLUSION: An elevated GLUT1 expression may be a useful predictor of distant recurrence and poor prognosis in rectal cancer patients after preoperative CRT. PMID- 22072149 TI - Clinical implications of the margin cytology findings and margin/tumor size ratio in patients who underwent pulmonary excision for peripheral non-small cell lung cancer. AB - PURPOSE: A pulmonary wedge resection is useful for the treatment of peripheral non-small cell lung cancer (NSCLC). The margin/tumor size ratio (M/T) is a predictor of positive margin cytology findings in these procedures, although the long-term clinical implications remain unclear. This relationship was investigated in this study. METHODS: Thirty-seven cases with a high surgical risk without additional pulmonary resection were selected from those accrued in a multicenter prospective study of optimal margin distance for pulmonary excision of peripheral NSCLC and followed for more than 5 years (range 5.3-14 years). RESULTS: Both the M/T and margin cytology findings were indicators of cancer recurrence and survival. All seven cases of surgical margin recurrence had a cytology-positive surgical margin. The 5-year survival rate was 54.2% (n = 24) for M/T < 1 and 84.6% for M/T >= 1 (n = 13, P = 0.05), while it was 38.5% for positive margin (n = 13) and 79.2% for negative margin (n = 24) cases (P = 0.001). In addition, the margin cytology findings were an independent prognostic factor. CONCLUSION: A pulmonary wedge resection for peripheral NSCLC should result in a negative malignant margin, which might be obtained from a sufficient tumor margin ratio of M/T >= 1. PMID- 22072150 TI - Successful surgical treatment of advanced follicular thyroid carcinoma with tumor thrombus infiltrating the superior vena cava: report of a case. AB - We report a case of advanced follicular thyroid carcinoma with massive involvement of the great veins of the cervix and mediastinum, and extensive tumor thrombus growing intraluminally into the superior vena cava. The patient, a 70 year-old Japanese woman, was treated successfully by a cooperative surgical team of endocrine and cardiovascular surgeons. Total thyroidectomy with thrombectomy was performed via a minimum phlebotomy in the right brachiocephalic vein, sacrificing only the right internal jugular vein, achieving complete primary tumor resection. She recovered quickly without any complications, and received (131)I radioisotope ablation for her multiple lung metastases. At the time of writing, more than 12 months after surgery, she was well. These treatments thus achieved progression-free survival without impairing her quality of life. Following the case report, we discuss the surgical indications for locally advanced thyroid carcinoma involving the great veins of the mediastinum by reviewing previous reports. PMID- 22072151 TI - Off-the-job training for VATS employing anatomically correct lung models. AB - We evaluated our simulated major lung resection employing anatomically correct lung models as "off-the-job training" for video-assisted thoracic surgery trainees. A total of 76 surgeons voluntarily participated in our study. They performed video-assisted thoracic surgical lobectomy employing anatomically correct lung models, which are made of sponges so that vessels and bronchi can be cut using usual surgical techniques with typical forceps. After the simulation surgery, participants answered questionnaires on a visual analogue scale, in terms of their level of interest and the reality of our training method as off the-job training for trainees. We considered that the closer a score was to 10, the more useful our method would be for training new surgeons. Regarding the appeal or level of interest in this simulation surgery, the mean score was 8.3 of 10, and regarding reality, it was 7.0. The participants could feel some of the real sensations of the surgery and seemed to be satisfied to perform the simulation lobectomy. Our training method is considered to be suitable as an appropriate type of surgical off-the-job training. PMID- 22072152 TI - Cost disparity between open repair and endovascular aneurysm repair for abdominal aortic aneurysm: a single-institute experience in Japan. AB - PURPOSE: We conducted this study to compare the cost of open surgical repair (OR) with that of endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm (AAA). METHODS: Between January 2007 and November 2008, 70 patients underwent open repair and 57 patients underwent EVAR. We evaluated the total cost, including that of the Diagnosis Procedure Combination (DPC), that of the surgical procedure, that of materials such as grafts and guide wires, and that of the anesthesia. RESULTS: The mean costs for OR versus EVAR were as follows: DPC, Y632,370 versus Y490,050, respectively, which was significant; anesthesia, Y123,540 versus Y86,220, respectively (P < 0.05); and materials, Y257,770 versus Y2,113,280, respectively (P < 0.05). Thus, the mean total cost was Y1,825,830 versus Y3,159,270 for open repair and EVAR, respectively (P < 0.05). CONCLUSIONS: New technologies should not only be clinically effective, but also cost effective. EVAR is less invasive clinically, but the cost of endovascular prostheses and other materials remains high. PMID- 22072153 TI - Poor sleep quality, stress status, and sympathetic nervous system activation in nondipping hypertension. PMID- 22072154 TI - Dielectrophoretic chip with multilayer electrodes and micro-cavity array for trapping and programmably releasing single cells. AB - Cell characterization analysis usually involves a sequence of steps such as culture, separation, trapping, examination and recollection. In general, it is difficult to recover the identified cells and achieve a multi-run examination on a single chip for clinical samples. In the present study, a dielectrophoresis (DEP) micro-device was developed for multi-step manipulations of cells at the single-cell level. The structure of the DEP chip consisted of an indium tin oxide (ITO) top electrode, a flow chamber, a middle electrode on an SU-8 surface, a micro-cavity array of SU-8 and distributed electrodes at the bottom of the micro cavities. The purpose of the three-layer-electrode design was threefold. First, cells could be trapped into the micro-cavities by negative DEP between the top and middle electrodes. After cells were trapped, cell analysis at the single-cell level could potentially be performed. This could include, for example, drug treatment or biomedical sensing on the chip without applying voltage. Once identified, the target cells could be individually released by controlling the bottom distributed electrodes. Finally, the rest of the trapped cells could be pulled out by a positive DEP force between the top and middle electrodes and flushed away for the next run of cell analysis. The multi-step manipulations of human bladder cancer cells (TSGH8301) were successfully demonstrated and discussed, providing an excellent platform technology for a lab-on-a-chip (LOC). PMID- 22072155 TI - The addition of amides to group 14 (di)-metallenes. AB - The addition of a series of primary and secondary amides to the group 14 (di)metallenes Mes(2)Si=SiMes(2), Mes(2)Ge=GeMes(2) and (Me(3)Si)(2)Si=C(OSiMe(3))R, where R = t-Bu or R = 1-Ad, was examined. In general, the addition of primary and N-methyl amides gave amide adducts whereas the addition of N-phenyl amides gave imidate adducts. The regiochemistry of the additions was highly dependent upon the substituent bonded to the amide nitrogen. We propose that the formation of the adducts proceeds by way of a zwitterionic intermediate. The reactivity of tetramesityldigermene towards amides is used to predict the structure of the amide adducts formed on the Ge(100)-2 * 1 surface. PMID- 22072156 TI - 15-Hydroxyprostaglandin dehydrogenase associates with poor prognosis in breast cancer, induces epithelial-mesenchymal transition, and promotes cell migration in cultured breast cancer cells. AB - Breast cancer is the most frequent cancer and the leading cause of cancer-related deaths in women worldwide. The prognosis of breast cancer is tightly correlated with the degree of spread beyond the primary tumour. Arachidonic acid (AA) and prostaglandin E(2) (PGE(2)) are known to regulate tumour metastasis enabling epithelial-mesenchymal transition (EMT). However, the detailed role of 15 hydroxyprostaglandin dehydrogenase (HPGD), the key enzyme degrading prostaglandin E(2) , remains unclear in breast cancer. Here, we show that HPGD mRNA is overexpressed in a subset of clinical breast cancers compared to normal breast tissue samples and that high HPGD mRNA expression associates with poor prognosis. Immunohistochemical staining of primary breast cancer and lymph node metastasis tissue samples confirmed high HPGD protein expression in 20% of the samples, as well as associated HPGD expression with aggressive characteristics, such as increased risk of disease relapse and shorter disease-free survival. Results from cultured cells indicated abundant HPGD expression in highly metastatic breast cancer cells, and impairment of HPGD expression using RNA interference led to a significant decrease in transforming growth factor-beta signalling, in cellular arachidonic acid levels as well as in cell migration. Furthermore, gene expression microarray analysis followed by quantitative RT-PCR validation showed that HPGD silencing decreased aryl hydrocarbon receptor signalling and induced mesenchymal-epithelial transition. In conclusion, our results indicate that HPGD is highly expressed in metastatic and aggressive breast cancer and promotes EMT and migration in breast cancer cells. PMID- 22072157 TI - Reversible severe deterioration of glycaemic control after withdrawal of metformin treatment. PMID- 22072159 TI - New Zealand is not an island when it comes to global health policy engagement. PMID- 22072160 TI - Sudden unexpected infant death--no more "stunned amazement"! PMID- 22072158 TI - Reduction of both beta cell death and alpha cell proliferation by dipeptidyl peptidase-4 inhibition in a streptozotocin-induced model of diabetes in mice. AB - AIMS/HYPOTHESIS: Incretins stimulate insulin secretion in a glucose-dependent manner but also promote pancreatic beta cell protection. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new glucose-lowering treatment that blocks incretin degradation by DPP-4. We assessed whether DPP-4 inhibition suppresses the progression to hyperglycaemia in a low-dose streptozotocin (STZ)-induced diabetic mouse model, and then investigated how DPP-4 inhibition affects islet function and morphology. METHODS: The DPP-4 inhibitor, des-fluoro-sitagliptin (SITA), was administered to mice during and after STZ injections, and in some mice also before STZ. RESULTS: In control mice, STZ resulted in hyperglycaemia associated with impaired insulin secretion and excess glucagon secretion. In SITA-treated STZ mice, these metabolic abnormalities were improved, particularly when SITA administration was initiated before STZ injections. We observed beta cell loss and dramatic alpha cell expansion associated with decreased insulin content and increased glucagon content after STZ administration. In SITA-treated mice, islet architecture and insulin content were preserved, and no significant increase in glucagon content was observed. After STZ exposure, beta cell apoptosis increased before hyperglycaemia, and SITA treatment reduced the number of apoptotic beta cells. Interestingly, alpha cell proliferation was observed in non-treated mice after STZ injection, but the proliferation was not observed in SITA-treated mice. CONCLUSIONS/INTERPRETATION: Our results suggest that the ability of DPP-4 inhibition to suppress the progression to STZ-induced hyperglycaemia involves both alleviation of beta cell death and alpha cell proliferation. PMID- 22072161 TI - Revised status of PSA testing in the early detection and treatment of prostate cancer. PMID- 22072162 TI - Temporal trends and clinical characteristics of spontaneous intracerebral haemorrhage in the Waikato region of New Zealand: a hospital-based analysis. AB - AIMS: To determine the incidence, and any change in incidence, of spontaneous intracerebral haemorrhage (ICH) detected in the hospitals of the Waikato region of New Zealand (NZ) between 1999 and 2008. To analyse clinical and patient parameters, and to correlate these with outcome. METHODS: A retrospective analysis was performed on patients presenting to Waikato and Thames Hospitals with ICH during the study period. Radiology reports, blood tests and the electronic clinical record were reviewed for each patient. RESULTS: 653 episodes of ICH were identified. The average annual incidence per 100,000 per year was 17.4 (16.1-18.7, 95% confidence interval). This increased from an average of 14.4 (13.7-15.1) between 1999-2001 to 21.4 (20.6-22.2) between 2006-2008 (rate ratio 1.49, p<0.0001). 249 (38.1%) patients died within 30 days of their sentinel bleed. The presence of intraventricular extension of bleed on neuroimaging (Odds Ratio (OR) 6.18, p<0.001), warfarin use (OR 1.11, p=0.76), warfarin use and intraventricular extension of bleed (OR 23.8, p=0.014), lobar location of bleed (OR 1.88, p=0.001) and age (OR 1.16 for every 10-year increase in age, p=0.02) increased the likelihood of death within 30 days. CONCLUSION: Observed ICH has increased in incidence in our hospitals over the past 10 years. Increasing availability of neuroimaging, increasing numbers of elderly, and increasing warfarin associated ICH were likely contributors to this observed increase. Radiological evidence of extension of intraventricular bleed, warfarin use, lobar location of bleed, and increasing age correlated with poorer survival. This data will be available for comparison with future studies to assess trends in incidence, patient characteristics and outcome in ICH. PMID- 22072163 TI - Secondary prevention of vertebral fractures in a large New Zealand District Health Board. AB - INTRODUCTION: International data suggests osteoporotic vertebral fractures are undertreated. The aim of this audit was to identify treatment gaps in patients with known vertebral fractures at Waitemata District Health Board (WDHB). METHODS: Retrospective review of patients admitted to WDHB from July 2006 to June 2007. Inclusion criteria were age over 65 years, admission to any service with a primary or secondary diagnosis of vertebral fracture. Exclusion criteria were fractures related to malignancy. Demographic data, details of vertebral fracture, and history of prior fractures were documented. Osteoporotic medications at admission and discharge were collected. RESULTS: We analysed 154 patients. The mean age was 81.5 years and 101 (66%) were women. At discharge, 42 (27%) of patients were on no treatment and 51 (33%) were treated with calcium, vitamin D and a bisphosphonate. Men were significantly more likely to be on no treatment (p<0.05). Lack of treatment did not appear to be associated with age or frailty. Subgroups studied included patients with prior non-vertebral fractures, primary diagnosis of vertebral fracture and patients on corticosteroids with rates of no treatment of 20%, 21% and 16% respectively. CONCLUSION: Secondary treatment of vertebral fractures in patients admitted to WDHB is suboptimal. Men were particularly affected. PMID- 22072164 TI - Emergency peripartum hysterectomy: a 10-year review in a tertiary obstetric hospital. AB - AIM: To evaluate the incidence, indications and complications associated with emergency peripartum hysterectomy (EPH) performed at Christchurch Women's Hospital, New Zealand. METHODS: A retrospective case series analysis of EPH from 2000-2009. Cases were identified using the hospital's computerised database. Those medical records were reviewed. EPH was defined as one performed for major postpartum haemorrhage unresponsive to other treatment within 24 hours of delivery. RESULTS: Nineteen EPH cases were identified among 47,520 deliveries, giving an incidence of 0.4 per 1000 deliveries. The indications were invasive placental adhesion--accreta, increta, percreta (63%), uterine atony (16%), placenta praevia (10.5%) and uterine tear with atony (10.5%). All cases of abnormal placentation in this study had previous caesareans or curettages. A significant association between previous uterine surgery and abnormal placentation was shown (p=0.02), especially those with previous caesarean (p=0.003). No maternal or perinatal mortality was recorded. Maternal morbidity was prevalent, including eight disseminated intravascular coagulopathies, seven intensive care, three bladder injuries, two re-explorations, one respiratory failure and one pulmonary embolism. CONCLUSION: Invasive placental adhesion is the major indication for EPH. This study demonstrates an association between the presence of scarred uteri as a result of previous uterine surgery, and abnormal placentation. PMID- 22072165 TI - Outcomes of patients with untreated severe aortic stenosis in real-world practice. AB - BACKGROUND: Surgical aortic valve replacement remains the gold standard of the treatment of severe symptomatic aortic stenosis but is often not considered due to excessive risk factors and comorbidities especially in elderly patients. We describe the burden of untreated severe aortic stenosis at a tertiary care hospital in New Zealand. METHOD: Consecutive patients with severe aortic stenosis presented between January-December, 2005 were studied retrospectively. Outcome assessment included mortality, hospital stay and on going symptoms (angina >CCS class II, dyspnoea >NYHA class II and syncope). RESULTS: A total of 105 patients with severe aortic stenosis were identified (mean age 76 plus or minus 13 years, 51% men). Patients were divided into 3 groups according to the management strategy. (Group 1: Not referred for surgery as asymptomatic (n=25), Group 2: Declined for surgery (n=41), Group 3: Accepted for surgery (n=39)). Median follow up was 34 months (interquartile range: 16-36 months). All-cause mortality in Group 1, Group 2 and Group 3 were 36%, 73% and 18% respectively while hospital days per 100 patient-years were 3.5, 10.1 and 6.4 and symptoms on last follow-up were 0%, 64% and 0% respectively. Almost half of symptomatic patients (Group 2 versus 3) were denied valve surgery due to comorbidities. Symptomatic patients had a significant mortality (p<0.0001) benefit with less hospitalisations (p<0.0001) post surgery. CONCLUSIONS: Untreated symptomatic severe aortic stenosis is associated with a poor prognosis and significant morbidity. For symptomatic patients with severe aortic stenosis who are denied surgery, alternative therapies such as transcatheter aortic valve implantation could be a viable option. PMID- 22072166 TI - Review of 100 consecutive microvascular free flaps. AB - AIM: To analyse the outcome of microvascular free flap reconstructions in Middlemore Hospital (South Auckland, New Zealand). METHOD: 100 consecutive free flap reconstructions from January 2004 to April 2010 were identified from the Middlemore Hospital Theatre Coding List. Basic patient demographics and indication for surgery along with free flap types were recorded and outcomes were analysed. RESULTS: The free flap success rate was 96%. There were 21 short term complications without any perioperative mortality. The most common complication was flap infection (7/21) followed by vascular thrombosis (6/21 venous and 1/21 arterial). Other complications included partial ischaemic flap (3/21), haematoma (2/21), venous congestion (1/21) and partial wound dehiscence (1/21). Fourteen flaps needed salvage procedures in the operating theatre including eight cases for re-anastomosis of vessels. The overall successful salvage rate was 71% resulting in four failures. The successful salvage rate following re-anastomosis of vessels was 63%. CONCLUSION: Overall success and salvage rates for free flap reconstructions at our plastics and reconstruction centre are comparable to that of international literature. Diligent postoperative monitoring and early return to theatre for re-exploration is the key to ensuring maximal free flap success. PMID- 22072167 TI - Colonic self-expanding metal stents (SEMS) in acute large bowel obstruction. AB - AIM: Colonic SEMS are increasing used in the management of acute large bowel obstruction, both as a bridge to surgery and as a definitive palliative measure in patients unfit for surgery. We describe our experience from a New Zealand hospital and compare our data with that already published in literature. METHODS: In this retrospective 4-year study, data was collected from the case notes of 28 consecutive patients with acute large bowel obstruction referred for colonic SEMS. Uncovered Boston Scientific colonic SEMS were placed endoscopically under fluoroscopic guidance. Technical success was considered as correct placement of stent after deployment and clinical success as the passage of flatus and faeces after stent insertion. Data was analysed using descriptive statistics. RESULTS: Our technical and clinical success rates were 90% and 88% respectively. The procedure was palliative in 15 patients and as a bridge to elective surgery in 13 cases. Procedure-related mortality was 7%. It was because of one early and one late perforation. The average length of stay post procedure was 2 days. Mean survival post stent insertion in the palliative group was 2.4 months and for those with a bridge to surgery was 14 months. CONCLUSION: n Our results support the data published from international centres in terms of deployment of SEMS in patients with acute large bowel obstruction, both as a bridge to surgery and as a definitive palliative measure. PMID- 22072168 TI - "Punching above its weight": why New Zealand must maintain leadership in global health. AB - As a small island nation, with a population of only 4.4 million, and geographically isolated from the centres of global power, New Zealand could be seen as of marginal relevance to the global health agenda. This paper argues that New Zealand has been and should remain a player in global health, even if current fiscal constraints may suggest otherwise. Involvement fits with our responsibilities and commitments in the Pacific region and our wider interests, including ethical international trade, security, global alliances and the fundamental protection of health. PMID- 22072169 TI - Hypnosedative access and risk of harm. AB - AIM: To review PHARMAC's decision, effective 1 September 2010, to remove the 1 month restriction on funded prescription of hypnotics and anxiolytics. METHOD: We consider the evidence for an association between access to these medicines and risk of harm. RESULTS: Prescription volumes and reported harms have both increased over the last decade in New Zealand; available studies and clinical experience suggest a causal link. Preliminary data collected since PHARMAC's funding change suggest an exacerbation of the problem. CONCLUSION: The decision to relax funding restrictions on hypnosedatives is expected to increase drug related harms in a sub-population of users. Improved pharmacovigilance could inform policy regarding these agents. PMID- 22072170 TI - Colonoscopy--a rare cause of pancreatitis. PMID- 22072171 TI - Incarceration of an inguinal hernia post urinary catheterisation. PMID- 22072172 TI - Medical image. Chilaiditi syndrome. PMID- 22072173 TI - Medical image. Xanthogranulomatous pyelonephritis. PMID- 22072174 TI - Potential social and psychological consequences of the Rena incident: lessons from an international perspective. PMID- 22072175 TI - End-of-term review of the New Zealand Government's response to climate change: a public health perspective. PMID- 22072176 TI - Banning pharmaceutical sponsorship: is ethical apartheid the right road ahead? PMID- 22072177 TI - Not for resuscitation orders--clarification is needed. PMID- 22072178 TI - Thames hospital. PMID- 22072179 TI - Playing with 'the public health'. PMID- 22072180 TI - Improving emergency department performance at Christchurch Hospital: an update. PMID- 22072181 TI - Eliminating tobacco point of sale displays: removing the retail detail from the devil. PMID- 22072183 TI - Consensus statement on the role of the doctor in New Zealand. PMID- 22072182 TI - Binge drinking is patterned by demographic and socioeconomic position in New Zealand: largest national survey to date. PMID- 22072184 TI - Oleoresin chemistry mediates oviposition behavior and fecundity of a tree-killing bark beetle. AB - Many herbivores are sensitive to the secondary chemistry of their host plants. However, the influence of pine secondary chemicals (monoterpenes) on bark beetle fitness is poorly understood. We tested the hypothesis that the monoterpene composition of the phloem oleoresin of ponderosa pine, Pinus ponderosa var scopulorum, mediates rates of host acceptance, oviposition behavior, and fecundity of the western pine beetle, Dendroctonus brevicomis. We performed reciprocal rearing experiments, controlling for the monoterpene composition (chemotype) of host material. We tested the effects of two geographically interspersed host chemotypes on beetles with unknown (wild) and known (reared F(1)) chemical histories. Host chemotype and insect chemical history did not affect rates of acceptance of host material by female beetles. Insect chemical history affected egg gallery construction, and beetles constructed egg galleries that were on average 24.3% longer when reared in host material that was chemically similar to their natal host material. However, mean egg gallery lengths did not differ between host chemotypes. Insect chemical history also influenced fecundity: F(1) beetles produced 52.7% more offspring on average when reared in host material that was chemically similar to their natal host. Our experiments demonstrate that the chemical history of bark beetles mediates egg gallery construction and fecundity, but not host acceptance. This implicates chemical history as a more important factor than host chemotype in the oviposition behavior and fecundity of D. brevicomis. PMID- 22072185 TI - The use of mass isotopomer distribution analysis to quantify synthetic rates of sex pheromone in the moth Heliothis virescens. AB - Although there has been much investigation of the steps involved in sex pheromone biosynthesis in moths, little is known about the kinetics of biosynthesis in vivo, primarily because there are few techniques suitable for studying the small amounts of pheromone produced without perturbing a female moth's normal physiology. In this paper, female Heliothis virescens moths fed on U-(13)C glucose were subjected to mass isotopomer distribution analysis, enabling calculation of fractional (FSR) and absolute (ASR) synthetic rates of the main pheromone component, (Z)-11-hexadecenal, at two different photoperiodic times: during the scotophase (when adults are sexually active) and during the photophase (when adults do not engage in mating behavior). FSRs differed substantially at the two times with, as expected, the greater rate occurring during the scotophase. After determining Z11-16:Ald pool sizes, ASR through the scotophase was calculated to be roughly 20 times greater than ASR in the photophase. These differences are consistent with the release/non-release of the pheromone biosynthesis-activating neuropeptide. This approach should facilitate determination of more quantitative measures of semiochemical production in moths and other sugar-feeding insects that synthesize semiochemicals from glycolytic metabolites. PMID- 22072186 TI - The influence of receptor-mediated interactions on reaction-diffusion mechanisms of cellular self-organisation. AB - Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. PMID- 22072187 TI - Gene polymorphisms contributing to hypertension in immunoglobulin A nephropathy. AB - BACKGROUND: Hypertension, which is affected by genetic and environmental factors, is one of the major risk factors for chronic kidney disease. Identification of the genetic factor contributing to hypertension in patients with chronic kidney disease may potentially refine a therapeutic strategy. METHODS: In the present multicenter cross-sectional study, 240 patients were eligible (aged 15-50 years with urinary protein >=0.25 g/day) out of 429 patients who were diagnosed as having immunoglobulin (Ig) A nephropathy (IgAN) by renal biopsy between 1990 and 2005 and enrolled in our previous study, PREDICT-IgAN. The outcome was hypertension defined as >=140 and/or >=90 mmHg of systolic and diastolic blood pressure and/or use of antihypertensives at renal biopsy. We assessed associations between hypertension and 28 polymorphisms with the frequency of minor genotype >=10% among 100 atherosclerosis-related polymorphisms using the Chi-squared test in dominant and recessive models. We identified polymorphisms associated with hypertension in multivariate logistic regression models. RESULTS: Baseline characteristics: hypertension 36.3%. Among 28 polymorphisms, the Chi squared test revealed that CD14 (-159CC vs CT/TT, P = 0.03) and ACE (DD vs DI/II, P = 0.03) were significantly associated with hypertension after Bonferroni correction. Multivariate logistic regression models revealed that CD14 -159CC [vs CT/TT, odds ratio (OR) 3.58 (95% confidence interval (CI) 1.66-7.63)] and ACE DD [vs DI/II, OR 4.41 (95% CI 1.80-10.8), P = 0.001] were independently associated with hypertension. CONCLUSIONS: CD14 C-159T and ACE I/D contributed to hypertension in patients with IgAN. PMID- 22072188 TI - Scavenger receptor expressions in the kidneys of mice with lipoprotein glomerulopathy. AB - BACKGROUND: To clarify whether dysfunction of the scavenger receptor (SR) participates in the development of lipoprotein glomerulopathy (LPG) in immunoglobulin F(c) receptor gamma chain (F(c)Rgamma)-deficient mice [F(c)Rgamma knock-out (KO) mice] with induced chronic graft-versus-host disease (cGVHD). METHOD: In wild-type (WT) and F(c)Rgamma KO C57BL/6 mice, cGVHD was induced by injection of lymphoid cells from donor Bm12 mice. At 6 months after injection, the mice were sacrificed and histologically examined. Total RNA was extracted from the kidneys and cytokine, chemokine, and SR transcript expressions were evaluated by reverse transcription-polymerase chain reaction. RESULTS: Three of 4 female cGVHD(+)/F(c)Rgamma KO mice presented LPG in >60% of glomeruli. cGVHD(-) and cGVHD(+)/WT mice did not show LPG. The SRs CD36, CD68, and CXCL16 showed a significant difference in the values of their transcripts between cGVHD(+)/WT and cGVHD(+)/F(c)Rgamma KO mice. Among them, only CD36 showed a drastic decline of mRNA expressions in cGVHD(+)/F(c)Rgamma KO mice. CONCLUSION: CD36 may play a crucial role in the development of LPG in F(c)Rgamma KO mice with cGVHD. In addition to the apolipoprotein E mutation, dysfunction of lipid clearance in the kidney might be one of the factors for the development of LPG. PMID- 22072189 TI - Indolizinones as synthetic scaffolds: fundamental reactivity and the relay of stereochemical information. AB - Indolizinones are under-explored N-heterocycles that react with exquisite chemo- and stereoselectivity. An exploration of the fundamental reactivity of these azabicycles demonstrates the potential to relay stereochemical information from the ring-fusion to newly formed stereocenters on the bicyclic core. The indolizinone diene undergoes selective hydrogenation and readily participates in Diels-Alder cycloadditions as well as ene reactions. The vinylogous amide embedded in the five-membered ring is resistant to reaction when the diene is in place. However, removal of the diene allows for diastereoselective hydrogenation of, and 1,4-additions to, the vinylogous amide. These fundamental reactions with indolizinones have provided a structurally diverse array of products that hold promise in the context of natural product synthesis. PMID- 22072190 TI - Compliance to service standards for congenital upper limb deficiency: the Northern Ireland experience. AB - BACKGROUND: In 2003, the British Society of Rehabilitation Medicine (BSRM) published guidelines on amputee and prosthetic rehabilitation, including those with congenital limb deficiency. OBJECTIVES: The aim of the study was to evaluate the service provided by the Regional Disablement Service (RDS) to children with congenital upper limb deficiency, against BSRM guidelines. STUDY DESIGN: Retrospective chart review. METHODS: Chart review. RESULTS: Analysis of the group (n = 44) showed 52% were male, with 61% of children affected on the left side, and 73% having a transverse deficiency. Compliance to individual aspects of the guidelines varied considerably. Only 14 (32%) of children had met with the multidisciplinary team by the recommended age of six months. Analysis of referral sources and timings suggested that children were initially seen elsewhere and later referred to RDS after consultation with a surgeon. CONCLUSIONS: RDS compliance with the BSRM guidelines was variable. Particularly disappointing was the low rate of children and families meeting the multidisciplinary team at an early age (< 6 months). The low rate of early referral prompted us to contact all paediatricians in Northern Ireland highlighting the guidelines, the benefits of early contact with RDS and encouraging referral on diagnosis. PMID- 22072191 TI - Persistent ulnar-sided wrist pain after treatment of triquetral dorsal chip fracture: six cases related to triangular fibrocartilage complex injury. AB - INTRODUCTION: Persistent ulnar-sided wrist pain after treatment of triquetral dorsal chip fracture even after union is a matter of concern. There could be various reasons for this persistent pain like arthritis, instability, fractures and non-union. We correlate our findings of physical examination and wrist arthroscopy as triangular fibrocartilage complex injury to be one of the causes of this persistent pain. PATIENTS: Six subjects who had persistent ulnocarpal joint pain and tenderness after triquetral dorsal chip fracture, despite 2 months of conservative treatment, were subjected to physical tests. If the physical examination yields positive results, then magnetic resonance imaging followed by arthroscopic treatment was performed. The six patients were then evaluated using the visual analogue scale, the Mayo modified wrist score, and the grip strength test. RESULTS: Triangular fibrocartilage complex (TFCC) injury was observed in all six cases and partial TFCC resection and synovectomy were performed. Analysis of the visual analogue scale, Mayo modified wrist score, and grip strength test data revealed statistically significant improvements (P < 0.05). CONCLUSION: In addition to several causes reported in the published literature, TFCC injury can be a cause of persistent ulnar pain after treatment of triquetral dorsal chip fracture. Arthroscopic partial TFCC resection can be considered to be a suitable treatment for such cases. PMID- 22072192 TI - Advances on the Masquelet technique using a cage and nail construct. AB - Traumatic, cancerous or infectious loss of bone is treated by either amputation or reconstruction. With limb salvage always preferable, surgeons rely on already established techniques such as grafting and distraction osteogenesis to avoid amputation, and ideally restore structure and thus function. The Masquelet technique is an effective method of bone reconstruction and limb salvage which is underreported in the English literature, and we report a case with advances using a cage and nail construct, resulting in successful eradication of methicillin resistant staphylococcus aureus infection and reconstitution of a 17 cm diaphyseal defect in the tibia. PMID- 22072193 TI - Precision of Ci-navigated extension and flexion gap balancing in total knee arthroplasty and analysis of potential predictive variables. AB - INTRODUCTION: The aim of this study was to evaluate the accuracy of final limb alignment and flexion-extension and medial-lateral gap balancing in computer navigated total knee arthroplasty and to analyze various possible predictive variables that may affect the gaps in computer navigated knee arthroplasty. MATERIALS AND METHODS: The DePuy Ci system, a nonimage-based passive optical computer navigation system, was used in 225 patients with knee osteoarthritis to assist for the total knee arthroplasty. From the raw data the Ci-verified pre- and postoperative leg axis in extension, angle of tibia and femur resection, the flexion and extension angle, the medial and lateral extension and flexion gaps were extracted; and differences in gaps were calculated and subjected to statistical analysis. Leg alignment and implant position were determined only by the navigation system. Preoperative variables were evaluated for their impact on the final flexion/extension and medial/lateral gaps achieved. RESULTS: Though the preoperative femoro-tibial coronal alignment had a large variance, postoperatively 98.22% of the knee was found to be between -3 degrees and +3 degrees in the coronal limb alignment axis. The Ci-verified femoral and tibial cuts in the coronal plane showed a good accuracy. The sagittal alignment of the femoral cut ranged from 8.20 degrees flexion to 3.20 degrees of extension. Rectangular extension and flexion gaps were achieved with <=3 mm of difference in gaps on medial and lateral sides in 98 and 93% of knees, respectively. Difference between extension and flexion gaps on the medial side was <=3 mm in 83% and on the lateral side in 84% of the knees. Of all the possible predictive variables analyzed, Pearson correlation and multiple regression analysis showed significant correlation only between the medial-lateral gap difference in extension and the Ci-verified femoral cut, tibial cut and limb axis, all in the coronal plane. CONCLUSION: Computer-assisted navigated total knee replacement allows for accurate gap balancing that is not dependent on the various pre- and intraoperative factors mentioned, including age, sex, Range of motion preoperative deformity and grade of osteoarthritis. The Ci-calculated and verified tibial, and femoral cuts are the only possible factors affecting the extension gap. PMID- 22072194 TI - Shuttling happens: soluble flavin mediators of extracellular electron transfer in Shewanella. AB - The genus Shewanella contains Gram negative gamma-proteobacteria capable of reducing a wide range of substrates, including insoluble metals and carbon electrodes. The utilization of insoluble respiratory substrates by bacteria requires a strategy that is quite different from a traditional respiratory strategy because the cell cannot take up the substrate. Electrons generated by cellular metabolism instead must be transported outside the cell, and perhaps beyond, in order to reduce an insoluble substrate. The primary focus of research in model organisms such as Shewanella has been the mechanisms underlying respiration of insoluble substrates. Electrons travel from the menaquinone pool in the cytoplasmic membrane to the surface of the bacterial cell through a series of proteins collectively described as the Mtr pathway. This review will focus on respiratory electron transfer from the surface of the bacterial cell to extracellular substrates. Shewanella sp. secrete redox-active flavin compounds able to transfer electrons between the cell surface and substrate in a cyclic fashion-a process termed electron shuttling. The production and secretion of flavins as well as the mechanisms of cell-mediated reduction will be discussed with emphasis on the experimental evidence for a shuttle-based mechanism. The ability to reduce extracellular substrates has sparked interest in using Shewanella sp. for applications in bioremediation, bioenergy, and synthetic biology. PMID- 22072196 TI - Reactivation characteristics of stored aerobic granular sludge using different operational strategies. AB - Aerobic granules after 6 months storage were employed in identical sequencing batch reactors (SBRs) using synthetic wastewater to investigate the impacts of different operational strategies on granules' reactivation process. The SBRs were operated under three operational strategies for reactivation of (a) different organic loading rate (OLR); (b) different ammonia concentration; and (c) different shear force (a superficial upflow air velocity). The results indicated that granules after long-term storage could be successfully recovered after 7 days of operation, and the excellent granule reactivation performance was closely related to the operational strategies, since inappropriate operational strategies could cause the outgrowth of filamentous bacteria and granule disintegration. Based on comprehensive comparison of reactivation performance under different operational strategies, the optimal operation strategy for granule reactivation was suggested at OLR of 0.8 kg COD/m(3)/day, ammonia concentration of 15-20 mg/L, and a superficial upflow air velocity of 2.6 cm/s. After 7 days operation under the optimal strategy, the dark brown granules (12 months storage) restored their bioactivities to previous state, in terms of COD removal efficiency (97.44%) and specific oxygen uptake rate (40.63 mg O(2)/g SS h(-1)). The results shed light on the future practical application of stored aerobic granules as bioseed for reactor fast start-up. PMID- 22072197 TI - Relapsed multiple myeloma presenting as an orbital plasmacytoma. PMID- 22072198 TI - Augmented kinetic observational proptometry: an improved technique for clinical assessment of proptosis and enophthalmos. PMID- 22072199 TI - Occult orbital organic foreign body. PMID- 22072200 TI - Re: "Isolated cavernous hemangioma of conjunctiva". PMID- 22072202 TI - Re: "Transconjunctival dacryocystorhinostomy: scarless surgery without endoscope and laser assistance". PMID- 22072204 TI - Re: "Orbital dissemination of Lemierre syndrome from gram-positive septic emboli". PMID- 22072206 TI - Re: "Comparison of free tarsoconjunctival grafts and Hughes tarsoconjunctival grafts for lower eyelid reconstruction". PMID- 22072208 TI - Re: "Indications for orbital imaging by the oculoplastic surgeon". PMID- 22072210 TI - Cosmetic botulinum toxin type A induced ptosis presenting as myasthenia. PMID- 22072211 TI - Ocular adnexal lymphoma of the extraocular muscles: case series from the University of Iowa and review of the literature. AB - PURPOSE: To review and statistically analyze the data of patients with discrete involvement of the extraocular muscles with ocular adnexal lymphoma from the tumor registry at the University of Iowa and to compile with current cases in the literature. METHODS: The records of patients with biopsy-proven orbital lymphoma at the University of Iowa Hospitals and Clinics Department of Ophthalmology and the Tumor Registry of the University of Iowa were reviewed. A review of the literature and meta-analysis were conducted. RESULTS: Eleven patients were identified with biopsy-proven ocular adnexal lymphoma with discrete involvement of the extraocular muscles at the University of Iowa. Additionally, 46 patients were identified in the literature with clinical and radiographic involvement of the extraocular muscles, 31 (67%) with biopsy-proven involvement. In the combined group of 57 patients, 16 (35%) of 45 patients with histopathologic documentation had lymphomas classified as extranodal marginal zone lymphomas. Twenty-five (67%) of the 37 patients with tumor-staging documentation had no extraorbital involvement. CONCLUSIONS: Ocular adnexal lymphoma with discrete extraocular muscle involvement is rare. Most lymphomas found in this area of the orbit are subtypes of B-cell lymphoma. This disease should be included in the differential diagnosis of enlarged extraocular muscles. PMID- 22072212 TI - Alteration in miRNA gene expression pattern in acute promyelocytic leukemia cell induced by arsenic trioxide: a possible mechanism to explain arsenic multi-target action. AB - MicroRNAs (miRNAs) are involved in cancer pathogenesis, apoptosis, and cell growth, and these miRNAs are thought to be functional as oncogenes and/or tumor suppressors in the gene regulatory networks. We studied the potential contribution of miRNAs in acute promyelocytic leukemia (APL) cell NB4 during the apoptosis induction by arsenic trioxide (ATO). The apoptotic effects of ATO on the NB4 cell line at a pharmacological dose (2 MUM) was verified using cell growth and viability assays, MTT assay, BrdU cell proliferation assay, flow cytometric analysis, and caspase-3 activity assay. miRNAs from untreated and 2 MUM ATO-treated NB4 cell line were extracted, purified, and converted to complementary DNAs. Differential expressions of 88 cancer-related miRNAs were analyzed by real-time reverse transcription PCR using miRNA PCR cancer-array system. After normalizing to the average Ct value of three housekeeping genes in the array (U6, SNORD47, and SNORD48), the fold change of miRNAs was calculated in the ATO-treated cells as compared to untreated. Among the 88 cancer-focused miRNAs, 51 miRNAs were found to be differentially expressed more than 2-fold after ATO treatment. Of these, 48 miRNAs were upregulated up to 21.65-fold changes, while three miRNAs were downregulated up to 5.19-fold changes. By screening the literature, a majority of these upregulated miRNAs were found to have tumor and/or metastatic suppressors' functions associated with cell cycle arrest and apoptosis, as well as inhibition of angiogenesis, invasion, and metastasis. Our results demonstrate that ATO, at the relevant concentration, modulate a substantial number of cancer-related miRNAs in APL cell line; most of these are known to function as a tumor and/or metastatic suppressors and have confirmed targets involved in cell cycle arrest and apoptosis. The results of this study support the hypothesis that miRNAs may play a mediatory role in eliciting the multi-target and pleiotropic action of ATO. PMID- 22072213 TI - The progranulin (GRN) Cys157LysfsX97 mutation is associated with nonfluent variant of primary progressive aphasia clinical phenotype. AB - The progranulin gene (GRN) g.10325_10331delCTGCTGT (relative to nt1 in NG_007886.1), alias Cys157LysfsX97, has been so far reported only once in a patient with frontotemporal dementia. Here, we describe a 63-year old patient carrying the same mutation, presenting with a 3-year history of language disorder, and diagnosed clinically with nonfluent variant of primary progressive aphasia according to current criteria. This patient's description expands the spectrum of clinical presentations of frontotemporal lobar degeneration caused by the GRN Cys157LysfsX97 mutation. PMID- 22072214 TI - A canine model to evaluate efficacy and safety of gamma-secretase inhibitors and modulators. AB - Gamma-secretase, a membrane bound protease which cleaves the transmembrane protein amyloid-beta protein precursor (AbetaPP), is a therapeutic target for Alzheimer's disease. Gamma-secretase inhibitors (GSIs) and modulators (GSMs) are being investigated as potential disease-modifying agents. Preclinical in vivo models to monitor the activity on gamma-secretase are described in different species such as mouse, rat, and guinea pigs. All these models have their value in testing compounds with amyloid lowering properties, however, compound characteristics and pharmacokinetic properties, as well as other species characteristics such as limited sampling volumes of cerebrospinal fluid (CSF), recommended the use of a larger, non-rodent animal species. For this purpose, a screening model in dogs was developed for testing GSIs and GSMs. We showed that GSIs and GSMs had a dose- and time-dependent effect on Abeta(37), Abeta(38), Abeta(40), and Abeta(42) in CSF. Changes in liver function were evidenced by a transient increase in bilirubin with the GSMs and incidental increases in alanine aminotransferase for GSMs as well as GSIs. Microarray analysis of liver biopsies enabled to elucidate potential mechanisms behind the liver function changes. The relevance of the liver findings should be further evaluated in chronic pre clinical safety studies and in humans. Based on our data, we can conclude that the dog is a very appropriate species to assess efficacy and safety of compounds which have an effect on AbetaPP processing such as GSMs, GSIs, and BACE inhibitors. PMID- 22072215 TI - Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients. AB - This study was performed to determine the incidence, risk factors, and prognostic implications of venous thromboembolism (VTE) in Asian patients with colorectal cancer (CRC). Differences in clinical characteristics and prognostic impact between extremity venous thrombosis (or deep-vein thrombosis; DVT)/pulmonary embolism (PE) and intra-abdominal venous thrombosis (IVT) were also evaluated. For this study, consecutive CRC patients (N = 2,006) were enrolled and analyses were conducted retrospectively. VTEs were classified into two categories (DVT/PE and IVT). Significant predictors of developing VTEs were advanced stage and an increased number of co-morbidities. The two-year cumulative incidence of DVT/PE was 0.3%, 0.9% and 1.4% in stages 0~1, 2 and 3, respectively; this incidence range of DVT/PE in Asian patients with loco-regional CRC was lower than in Western patients. However, the two-year incidence (6.4%) of DVT/PE in Asian patients with distant metastases was not lower than in Western patients. Although 65.2% of patients with DVT/PE were symptomatic, only 15.7% of patients with IVT were symptomatic. During chemotherapy, DVT/PE developed more frequently than IVT. Only DVT/PE had a negative effect on survival; IVT had no prognostic significance. In conclusion, despite the low incidence of DVT/PE in Asian patients with loco-regional CRC, the protective effect of Asian ethnicity on VTE development disappears as tumour stage increases in patients with distant metastases. Considering different clinical characteristics and prognostic influences between DVT/PE and IVT, the treatment approach should be also different. PMID- 22072216 TI - Characteristics of the three ligaments of human spring ligament complex from a viewpoint of elements. AB - To elucidate characteristics of the three ligaments constituting the spring ligament complex from a viewpoint of elements, the authors investigated age related changes of elements, relationships among their elements, relationships among ligaments in the elements, and gender differences in the three ligaments of the spring ligament complex, the superomedial calcaneonavicular (SMCN), inferoplantar longitudinal calcaneonavicular (ICN), and third or medioplantar oblique calcaneonavicular (TCN) ligaments. After ordinary dissection at Nara Medical University was finished, the SMCN, ICN, and TCN ligaments of the spring ligament complex were removed from the subjects. The subjects consisted of 10 men and 12 women, ranging in age from 62 to 99 years (average age = 80.5 +/- 9.7 years). After incineration with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that although the Ca and P content hardly changed in the SMCN ligament with aging, the Ca and P content in the ICN ligament increased to about three and five times higher in the 80s in comparison with the 60s, respectively, whereas in the TCN ligament, it increased about 40% and 90% higher in the 80s compared with the 60s, respectively. Regarding the relationships among elements, significant direct correlations were found among the contents of Ca, P, and Mg in all the three ligaments of the spring ligament complex. This finding was in agreement with the previous finding obtained with the three ligaments of the anterior cruciate ligament, posterior longitudinal ligament, and ligamentum capitis femoris. Whether there were significant correlations among the three ligaments of the spring ligament complex with regard to the Ca, P, S, Mg, Zn, and Fe contents was examined using Pearson's correlation. It was found that there were significant direct correlations between the SMCN and TCN ligaments in all the Ca, P, Mg, and Zn contents and also between the SMCN and ICN ligaments in both the Mg and Fe contents but not between the TCN and ICN ligaments in the six element contents. Regarding the gender difference in elements, a significant gender difference was found only in the Mg content of the SMCN ligament, being significantly higher in men than in women. PMID- 22072217 TI - Mothers' responses to children's negative emotions and child emotion regulation: the moderating role of vagal suppression. AB - The current study examined the moderating effect of children's cardiac vagal suppression on the association between maternal socialization of negative emotions (supportive and nonsupportive responses) and children's emotion regulation behaviors. One hundred and ninety-seven 4-year-olds and their mothers participated. Mothers reported on their reactions to children's negative emotions and children's regulatory behaviors. Observed distraction, an adaptive self regulatory strategy, and vagal suppression were assessed during a laboratory task designed to elicit frustration. Results indicated that children's vagal suppression moderated the association between mothers' nonsupportive emotion socialization and children's emotion regulation behaviors such that nonsupportive reactions to negative emotions predicted lower observed distraction and lower reported emotion regulation behaviors when children displayed lower levels of vagal suppression. No interaction was found between supportive maternal emotion socialization and vagal suppression for children's emotion regulation behaviors. Results suggest physiological regulation may serve as a buffer against nonsupportive emotion socialization. PMID- 22072218 TI - Advantages of intra-capsular micro-enucleation of schwannoma arising from extremities. AB - BACKGROUND: Schwannoma is the most common tumor of the peripheral nerves, with surgical enucleation being the established treatment modality. However, some schwannomas cannot be easily enucleated and this sometimes results in iatrogenic nerve injury even with atraumatic procedures. Here we present a retrospective review of the management of schwannoma in the extremities and compare clinical outcomes from the two techniques of extra-capsular and intra-capsular enucleation. METHODS: We reviewed 36 schwannomas from 35 patients who underwent surgical excision of schwannomas arising from the extremities. Twenty had undergone extra-capsular resection and 16 had undergone enucleation using the intra-capsular technique. The post-operative neurological deficits were graded as minor, major, and transient. The duration of symptoms, maximum tumor diameter and site of occurrence were compared between patients with the three grades of deficit. RESULTS: In total, 22 patients developed no sensory changes following enucleation of schwannoma or only temporary and minor changes that had fully resolved within 6 months. Ten patients developed new neurological deficits following surgery that took longer than 6 months to resolve. Four patients experienced new motor deficits or paresthesia following operation that had still not recovered at the final follow-up, all of whom underwent enucleation using the extra-capsular technique. Neurological deficit after enucleation was significantly lower using the intra-capsular compared with the extra-capsular technique. Patient age, duration of symptoms, maximum diameter of the tumor and site of occurrence did not influence the neurological deficit following enucleation of schwannoma. CONCLUSION: These results support intra-capsular micro enucleation as a safe and reliable treatment for every type of schwannoma. To minimize the risk of nerve injury, en bloc resection should not be used because the main purpose of schwannoma surgery is the relief of symptoms, not tumor resection. Thorough pre-operative counseling of patients to inform them of the potential occurrence of neurological deficit is important. PMID- 22072219 TI - Authors' response to the Schaller's comment, "how eloquent is eloquent?". PMID- 22072220 TI - Assessment of sorbent impregnated PUF disks (SIPs) for long-term sampling of legacy POPs. AB - Two field studies were conducted for one year using sorbent-impregnated polyurethane foam (SIP) disks for PCB and PBDE air sampling. SIP disks were introduced by Shoeib et al. (2008) as an alternative passive air sampling medium to the polyurethane foam (PUF) disk and have the advantage of a higher holding capacity for organic chemicals. The first study on SIP disks confirmed their application for measuring volatile perfluorinated compounds (PFCs) and their ability to maintain time-integrated (linear) air sampling. In this study, the suitability of the SIP disks for long-term sampling of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and hexachlorobenzene (HCB) was assessed. SIP disks were deployed at a rural site in the UK and harvested after periods ranging from 35-350 days. Atmospheric POP concentrations were monitored with a high-volume air sampler during the deployment period. Linear uptake was observed for all monitored PCBs and PBDEs over the full exposure time. Air sampler equilibrium was observed for HCB after 6 months. In a second field study, SIP disks were deployed for one year at 10 sites on a latitudinal transect in the UK and Norway, at which air sampling has been undertaken previously with different passive air sampling media since 1994. The estimated concentrations and spatial distributions derived from the SIP disks were largely in agreement with previously reported data. PMID- 22072221 TI - Why mammography screening has not lived up to expectations from the randomised trials. AB - We analysed the relation between tumour sizes and stages and the reported effects on breast cancer mortality with and without screening in trials and observational studies. The average tumour sizes in all the trials suggest only a 12% reduction in breast cancer mortality, which agrees with the 10% reported in the most reliable trials. Recent studies of tumour sizes and tumour stages show that screening has not lowered the rate of advanced cancers. In agreement with this, recent observational studies of breast cancer mortality have failed to find an effect of screening. In contrast, screening leads to serious harms in healthy women through overdiagnosis with subsequent overtreatment and false-positive mammograms. We suggest that the rationale for breast screening be urgently reassessed by policy-makers. The observed decline in breast cancer mortality in many countries seems to be caused by improved adjuvant therapy and breast cancer awareness, not screening. We also believe it is more important to reduce the incidence of cancer than to detect it 'early.' Avoiding getting screening mammograms reduces the risk of becoming a breast cancer patient by one-third. PMID- 22072222 TI - Preparation of a Highly Fluorophilic Phosphonium Salt and its Use in a Fluorous Anion-Exchanger Membrane with High Selectivity for Perfluorinated Acids. AB - Fluorous solvents are the most nonpolar, nonpolarizable phases known, whereas ions are inherently polar. This makes it difficult to create salts that are soluble in a fluorous solvent. Here we present the synthesis and characterization of a new fluorophilic phosphonium salt, tris{3,5 bis[(perfluorooctyl)propyl]phenyl}methylphosphonium methyl sulfate. The salt has a solubility of at least 14 mM in perfluoro(perhydrophenanthrene), perfluoro(methylcyclohexane), and perfluorohexanes. It also shows immediate potential for use as a phase-transfer catalyst in fluorous biphasic catalysis, but in this work it is used as an anion exchanger site in the first potentiometric fluorous-membrane anion-selective electrode. The membrane sensor exhibited the exceptional selectivity of 3.9 * 10(10) to 1 for perfluorooctanesulfonate over chloride, and of 2.5 * 10(7) to 1 for perfluorooctanoate over chloride. With improvements to the sensor's detection limit and lifetime, it has the potential to be an attractive alternative to the expensive, time-consuming methods currently employed for measurement of perfluorinated acids. PMID- 22072223 TI - Posttraumatic stress and tendency to panic in the aftermath of the chlorine gas disaster in Graniteville, South Carolina. AB - PURPOSE: Relatively little is known about psychological effects of environmental hazard disasters. This study examines the development of posttraumatic stress (PTS) and tendency to limited panic attack after a large chlorine spill in a community. METHODS: In January 2005, a large chlorine spill occurred in Graniteville, SC. Acute injuries were quantified on an ordinal severity scale. Eight to ten months later, participating victims completed the Short Screening Scale for PTSD (n = 225) and the Holden Psychological Screening Inventory (HPSI) (n = 193) as part of a public health intervention. Forced expiratory volume in 1 s (FEV(1)) and forced vital capacity were likewise measured via spirometry. Two sets of univariate logistic regression models were fit to detect independent effects of each potential covariate and risk factor on PTS score and tendency to panic. A supplemental analysis examined whether poor lung function may be a confounder and/or effect modifier of the effect of acute injury on PTS score and panic. RESULTS: Of those who completed psychological screening, 36.9% exhibited PTS symptoms. FEV(1), acute injury, and the HPSI psychiatric subscale were independently associated with increased PTS score. Acute injury severity scale and female sex were associated with tendency to panic. Immediate acute injury severity and poor lung function later were independently associated with PTS symptomotology. CONCLUSIONS: The high prevalence of PTS and endorsement of tendency to panic within our sample show a need for mental health treatment after a chemical hazard disaster. Mental health personnel should be considerate of those with serious physical injuries. PMID- 22072224 TI - Civil commitment law, mental health services, and US homicide rates. AB - PURPOSE: The study considers whether involuntary civil comment (ICC) statute provisions are associated with homicide rates. Do statutes based solely upon dangerousness criteria versus broader ICC-criteria-i.e. "need for treatment," "protection of health and safety," and family protection-have differential associations related to their goal of reducing the frequency of homicide? METHOD: State-level data were obtained from online data bases and key-informant surveys. Ordinary-least-squares and Poisson regression were used to evaluate the association between statute characteristics, mental health system characteristics, and 2004 Homicide Rates after controlling for firearm-control law restrictiveness and social-economic-demographic-geographic-and-political indicators historically related to homicide rate variation. RESULTS: Poisson and OLS models, respectively, were significant: likelihood ratio chi(2) = 108.47, df = 10; p < 0.000 and Adj. R (2) = 0.72; df = 10, 25; F = 10.21; p < 0.000. Poisson results indicate that social-economic-demographic-geographic-and-political indicators had the strongest association with state homicide rates (p < 0.000). Lower rates were associated with: broader ICC-criteria (p <= 0.01), fewer inpatient-bed access problems (p <= 0.03), and better mental health system ratings (p <= 0.04). OLS results indicate that social-economic-demographic geographic-and-political indicators accounted for 25% of homicide rate variation. Broader ICC-criteria were associated with 1.42 less homicides per 100,000. Less access to psychiatric inpatient-beds and more poorly rated mental health systems were associated with increases in the homicide rates of 1.08 and 0.26 per 100,000, respectively. CONCLUSIONS: While social-economic-demographic-geographic and-political indicators show the strongest association with homicide rate variation, the results show the importance and potentially preventive utility of broader ICC criteria, increased psychiatric inpatient-bed access, and better performing mental health systems as factors contributing to homicide rate variation. PMID- 22072225 TI - Successful management of severe blunt hepatic trauma by angiographic embolization. AB - We present the case of an 18-year-old female with severe liver trauma after a motorcycle accident. Due to initial hemodynamic instability, fluid resuscitation and transfusion of two units of red packed cells was required. After stabilization, a CT scan was performed, showing grade V liver injuries according to the American Association for the Surgery of Trauma grading system. Angiography revealed multiple extravasations during the early arterial phase, as well as active extravasation from the proximal left hepatic artery in the late arterial phase. The patient was successfully treated by arterial embolization using metal microcoils, after which no further need for blood transfusion ensued. This report highlights that, in carefully selected cases, arterial embolization can improve the clinical condition of patients, reduce the need for blood transfusion and lessen the possibility of an operation, even if severe liver trauma has ensued. PMID- 22072226 TI - Development of germinoma during the treatment of systemic-onset juvenile idiopathic arthritis with infliximab. AB - We report a 19-year-old patient with systemic-onset juvenile idiopathic arthritis (JIA) who developed a mediastinal germinoma during treatment with infliximab. Although the cancer risk of infliximab is controversial, this agent may have accelerated the growth of the germinoma. We conclude that the indications for tumor necrosis factor (TNF) inhibitors should be strictly decided and that a nationwide cohort study is necessary to assess the risk of cancer in patients with JIA exposed to biologics. PMID- 22072227 TI - Development of novel nanocarrier-based near-infrared optical probes for in vivo tumor imaging. AB - Optical imaging with near-infrared (NIR) fluorescent probes is a useful diagnostic technology for in vivo tumor detection. Our plan was to develop novel NIR fluorophore-micelle complex probes. IC7-1 and IC7-2 were synthesized as novel lipophilic NIR fluorophores, which were encapsulated in an amphiphilic polydepsipeptide micelle "lactosome". The fluorophore-micelle complexes IC7-1 lactosome and IC7-2 lactosome were evaluated as NIR fluorescent probes for in vivo tumor imaging. IC7-1 and IC7-2 were synthesized and then encapsulated in lactosomes. The optical properties of IC7-1, IC7-2, IC7-1 lactosome and IC7-2 lactosome were measured. IC7-1 lactosome and IC7-2 lactosome were administered to tumor-bearing mice, and fluorescence images were acquired for 48 h. IC7-1 and IC7 2 were successfully synthesized in 12% and 6.3% overall yield, and maximum emission wavelengths in chloroform were observed at 858 nm and 897 nm, respectively. Aqueous buffered solutions of IC7-1 lactosome and IC7-2 lactosome showed similar fluorescence spectra in chloroform and higher or comparable quantum yields and higher photostability compared with ICG. Both lactosome probes specifically visualized tumor tissue 6 h post-administration. IC7-1 lactosome and IC7-2 lactosome could be promising NIR probes for in vivo tumor imaging. PMID- 22072228 TI - Probing the interior of self-assembled caffeine dimer at various temperatures. AB - The self-assembly of non-toxic well-consumed small caffeine molecules into well defined structures has important implications for future medical applications seeking to target the transport of small drugs in human body. Particularly, the solvation of the microenvironments of the self assembly ultimately dictates the interaction with the drug molecules and their therapeutic efficacy. We present femtosecond-resolved studies of the dynamics of aqueous solvation within self assembled dimeric structure of caffeine molecules. We have placed small hydrophobic probes 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl) 4H pyran (DCM), coumarin 500 (C500) into the caffeine dimer to enable spectroscopic examinations of the interior. While molecular modeling and NMR studies of the probes in the caffeine dimers reveal a well-defined location (stacked in between two caffeine molecules), dynamical light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, densimetric and sonometric experiments explore the structural evolution of the dimer upon complexation with the probes. We have extended our studies in various temperatures in order to explore structural evolution of the self assembled structure and consequently the dynamics of solvation in the interior of the dimer. Picoseconds/femtosecond resolved dynamics and the polarization gated spectroscopic studies unravel the hydration and energetics associated with activated viscous flow of the confined probes. Our studies indicate that the interior of the caffeine dimer is well-solvated; however, the dynamics of solvation is retarted significantly compared to that in bulk water, clearly revealing the dimers maintain some ordered water molecules. We have also explored the consequence of the retarded dynamics of solvation on the photo-induced electron transfer (ET) reaction of a model probe, 2-(p toluidino) naphthalene-6-sulfonate (TNS) encapsulated in the dimer. PMID- 22072229 TI - Elevated soluble receptor for advanced glycation end product levels in patients with acute coronary syndrome and positive cardiac troponin I. AB - OBJECTIVES: High levels of soluble receptor for advanced glycation end products (sRAGE) have been shown to have an atheroprotective role; however, no data are available on this molecule in acute coronary syndromes (ACS). We evaluated sRAGE levels in patients with non-ST segment elevation ACS (NSTE-ACS) or with chronic stable angina. METHODS: We studied 265 patients, 190 of whom had NSTE-ACS and 75 had chronic stable angina. RESULTS: Plasma sRAGE values were comparable in the two groups (P=0.19). However, in the patients with NSTE-ACS, sRAGE levels were significantly higher in patients with cardiac troponin-I (cTnI) of more than or equal to 0.04 ug/l compared with those with cTnI of less than 0.04 ug/l [758 (493 1536 ) pg/ml vs. 454 (167-899) pg/ml; P=0.0037]. A significant correlation (r=0.323, P=0.0045) was found between sRAGE and cTnI levels in patients with NSTE ACS. CONCLUSION: Plasma sRAGE levels are elevated in patients with NSTE-ACS with positive cTnI, suggesting that they could be related to myocardial cell damage. PMID- 22072230 TI - Bibliography-editors' selection of current world literature. PMID- 22072231 TI - The structure-function relationship of activated protein C. Lessons from natural and engineered mutations. AB - Protein C is the central enzyme of the natural anticoagulant pathway and its activated form APC (activated protein C) is able to proteolyse non-active as well as active coagulation factors V and VIII. Proteolysis renders these cofactors inactive, resulting in an attenuation of thrombin formation and overall down regulation of coagulation. Presences of the APC cofactor, protein S, thrombomodulin, endothelial protein C receptor and a phospholipid surface are important for the expression of anticoagulant APC activity. Notably, APC also has direct cytoprotective effects on cells: APC is able to protect the endothelial barrier function and expresses anti-inflammatory and anti-apoptotic activities. Exact molecular mechanisms have thus far not been completely described but it has been shown that both the protease activated receptor 1 and EPCR are essential for the cytoprotective activity of APC. Recently it was shown that also other receptors like sphingosine 1 phosphate receptor 1, Cd11b/CD18 and tyrosine kinase with immunoglobulin-like and EGF-like domains 2 are likewise important for APC signalling. Mutagenesis studies are being performed to map the various APC functions and interactions onto its 3D structure and to dissect anticoagulant and cytoprotective properties. The results of these studies have provided a wealth of structure-function information. With this review we describe the state-of-the-art of the intricate structure-function relationships of APC, a protein that harbours several important functions for the maintenance of both humoral and tissue homeostasis. PMID- 22072232 TI - Lifestyle and metabolic approaches to maximizing erectile and vascular health. AB - Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity. PMID- 22072233 TI - Long-term effects of differential early rearing in rhesus macaques: behavioral reactivity in adulthood. AB - Adverse early experiences are associated with a range of deleterious health outcomes in humans, including higher risk for affective disorders. Studies using a long-standing model of nonhuman primate model of early adversity have demonstrated that nursery-reared (NR) monkeys exhibit alterations in multiple aspects of biobehavioral development; however, few studies have evaluated the persistence of socioaffective behavioral changes through adulthood. We evaluated the effects of early rearing experience on adult animals' response to a well validated assessment of anxiety-like behavior, the human intruder paradigm (HIP). We tested 22 rhesus monkeys who were either nursery-reared (NR) or reared with their mothers (mother-reared; MR). NR monkeys were inhibited in their behavior compared to MR monkeys, with reduced locomotion and exploratory behaviors. NR animals showed a marginal increase in freezing. Together these findings demonstrate that the consequences of differential infant rearing experience on socioaffective behavior persist into adulthood, with evidence of greater inhibition in NR monkeys. PMID- 22072234 TI - Tissue repair driven by two different mechanisms of growth factor plasmids VEGF and NGF in mice auricular cartilage: regeneration mediated by administering growth factor plasmids. AB - The focus of this study was to compare the role of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in the regeneration of experimental skin and cartilage trauma. The role of VEGF in this process is known since decade; the NGF participation on this process has been first discussed within the spinal cord injury repair. We hypothesized that both VEGF and NGF induce angiogenesis and take part on the repair process. The angiogenesis response and the cartilage regeneration after phVEGF(165) plasmid and rat pcNGF plasmid administration were investigated using BALB/c mice. PhVEGF(165) and pcNFG were injected into the right mice ear and plain vector injection into the left ear the day before trauma. The next day, all mice were ear-punched, resulting in 2-mm diameter puncture through the center of both pinnae. In BALB/c mouse strain, a significantly faster cartilage repair was observed after phVEGF(165) and pcNGF injection into punched ear area in comparison to the control group. It has been shown that the healing process is after VEGF and NGF injection driven differentially. In case of VEGF is the cartilage wound repaired by induction of new chondrocytes differentiation. In the case of NGF, the regeneration is supported by immature leukocytes attracted into the punched area. The leukocytes induct angiogenesis so far indirectly by inflammation. The NGF-induced inflammation environment may be a part of mosaic creating the complete picture of regeneration. PMID- 22072236 TI - Engineering stem cells for treatment of osteochondral defects. PMID- 22072235 TI - Caveolin-1 overexpression is associated with hepatocellular carcinoma tumourigenesis and metastasis. AB - Caveolin-1 (Cav1) has been implicated in diverse human cancers, yet its role in hepatocellular carcinoma (HCC) tumourigenesis and metastasis remains elusive. In the current study, we aim to provide a comprehensive understanding regarding the functional role of Cav1 in HCC tumourigenesis and metastasis. Cav1 expression was examined in a panel of human HCC cell lines using western blotting analysis and quantitative RT-PCR and human tissues by immunohistochemistry. Cav1 was not detected in normal liver cell line and all non-tumourous liver tissues but exclusively expressed in HCC cell lines and tissues. Dramatic expression of Cav1 was found in metastatic HCC cell lines and tumours, indicating a progressive increase of Cav1 expression along disease progression. Cav1 overexpression was significantly correlated with venous invasion (p = 0.036). To investigate the functions of Cav1 in HCC, Cav1 overexpressing and knockdown stable clones were established in HCC cells and their tumourigenicity and metastatic potential were examined. Overexpression of Cav1 promoted HCC cell growth, motility, and invasiveness, as well as tumourigenicity in vivo. Conversely, knockdown of Cav1 in metastatic HCC cells inhibited the motility and invasiveness and markedly suppressed the tumour growth and metastatic potential in vivo. Collectively, our findings have shown the exclusive expression of Cav1 in HCC cell lines and clinical samples and revealed an up-regulation of Cav1 along HCC progression. The definitive role of Cav1 in promoting HCC tumourigenesis was demonstrated, and we have shown for the first time in a mouse model that Cav1 promotes HCC metastasis. PMID- 22072237 TI - Radiographically occult femoral and pelvic fractures are not mutually exclusive: a review of fractures detected by MRI following low-energy trauma. AB - OBJECTIVES: The purpose of this study was to review the MRI examinations of a large group of low-energy trauma patients in whom pelvic MRI had detected radiographically occult fractures, in order to characterize prevailing fracture patterns and determine how often co-existing proximal femoral and pelvic fractures were observed. METHODS: All patients having pelvic MRI over 5 years were identified. Word-search software selected 269 MRI reports containing the term 'fracture'. Further scrutiny identified 168 with diagnosis of fracture. MRI request and imaging record review identified 102 low-energy trauma cases that had MRI for clinical suspicion of fracture despite normal radiographs. Sixty-six cases were excluded for the following reasons: no expressed clinical suspicion of occult fracture; history suggesting high-energy trauma;skeletal co-morbidity hindering acute fracture identification;interval more than 2 weeks between radiographs and MRI. The 102 study MRI examinations, which employed a limited two sequence protocol, were reviewed. Any fracture that had not been appreciated on radiographs was recorded and characterized as femoral, pelvic, or co-existing femoral and pelvic fractures. RESULTS: The 102 study cases had a median age of 82 years.The median interval between pelvic radiographs and MRI was 3 days. MRI showed undiagnosed femoral fracture in 48/102 cases (47.1%), sacral fracture in 41/102 (40.2%),and pubic fracture in 55/102 (53.9%). In 11/102 cases(10.8%), MRI showed undiagnosed fractures of both proximal femur and pelvic ring (seven sacral, six pubic bone, two other site fractures). In 10/11 cases with coexisting femoral and pelvic fractures, the femoral fracture was incomplete. CONCLUSIONS: Limited pelvic MRI found a high prevalence of radiographically occult femoral and pelvic fractures in low-energy trauma patients, with clinical suspicion of fracture despite normal radiographs. Co-existing occult femoral and pelvic ring fractures were commonly observed, and in such cases, the femoral fracture was likely to be incomplete and multiple pelvic fractures were typically present. PMID- 22072238 TI - A 14-year-old with lateral knee pain and locking. PMID- 22072239 TI - Diagnostic accuracy of 18F-FDG-PET and PET/CT in patients with Ewing sarcoma family tumours: a systematic review and a meta-analysis. AB - OBJECTIVE: To systematically review and meta-analyse literature data on the diagnostic performance of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) in patients with Ewing sarcoma family tumours (ESFT). MATERIALS AND METHODS: PubMed/MEDLINE, Embase and Scopus databases were searched for articles that evaluated FDG-PET and PET/CT in patients with ESFT from inception to 31 May 2011. Studies that fulfilled the three following criteria were included in the systematic review: FDG-PET or PET/CT performed in patients with ESFT; articles about the diagnostic accuracy of FDG-PET and PET/CT; sample size of at least 10 patients with ESFT were included. Studies in which there were sufficient data to reassess sensitivity and specificity of FDG-PET or PET/CT in ESFT were included in the meta-analysis, excluding duplicate publications. Finally, pooled sensitivity, pooled specificity and area under the receiver operating characteristic (ROC) curve of FDG-PET or PET/CT in ESFT were calculated. RESULTS: We found 13 studies comprising a total of 342 patients with ESFT. The main findings of the studies included are presented. The meta-analysis of five selected studies provided these results about FDG-PET and PET/CT in ESFT: pooled sensitivity: 96% (95% confidence interval [CI] 91-99%); pooled specificity: 92% (95% CI 87-96%); area under the ROC curve: 0.97. CONCLUSION: With regard to the staging and restaging of patients with ESFT, the sensitivity, specificity and accuracy of FDG-PET and PET/CT are high; the combination of FDG-PET or PET/CT with conventional imaging is a valuable tool for the staging and restaging of ESFT and has a relevant impact on the treatment strategy plan. PMID- 22072240 TI - Percutaneous radiofrequency ablation of primary intraosseous spinal glomus tumor. AB - The glomus tumor is a rare, benign, but painful vascular neoplasm arising from the neuromyoarterial glomus. Primary intraosseous glomus tumor is even rarer, with only about 20 cases reported in the literature so far, 5 of which involved the spine. Surgical resection is currently considered the treatment of choice. We herewith present an uncommon case of primary intraosseous spinal glomus tumor involving the right pedicle of the eleventh thoracic vertebra (T11). To our knowledge, this is the first case of primary intraosseous spinal glomus tumor successfully treated by percutaneous CT-guided radiofrequency ablation (RFA). PMID- 22072241 TI - Fuel cell-powered microfluidic platform for lab-on-a-chip applications. AB - The achievement of a higher degree of integration of components--especially micropumps and power sources--is a challenge currently being pursued to obtain portable and totally autonomous microfluidic devices. This paper presents the integration of a micro direct methanol fuel cell (MUDMFC) in a microfluidic platform as a smart solution to provide both electrical and pumping power to a Lab-on-a-Chip system. In this system the electric power produced by the fuel cell is available to enable most of the functionalites required by the microfluidic chip, while the generated CO(2) from the electrochemical reaction produces a pressure capable of pumping a liquid volume through a microchannel. The control of the fuel cell operating conditions allows regulation of the flow rate of a liquid sample through a microfluidic network. The relation between sample flow rate and the current generated by the fuel cell is practically linear, achieving values in the range of 4-18 MUL min(-1) while having an available power between 1 4 mW. This permits adjusting the desired flow rate for a given application by controlling the fuel cell output conditions and foresees a fully autonomous analytical Lab-on-a-Chip in which the same device would provide the electrical power to a detection module and at the same time use the CO(2) pumping action to flow the required analytes through a particular microfluidic design. PMID- 22072242 TI - Message from the President of ASCI. Preface. PMID- 22072243 TI - Comparison of magnetic resonance imaging findings in non-ST-segment elevation versus ST-segment elevation myocardial infarction patients undergoing early invasive intervention. AB - To define causes and pathological mechanisms underlying differences in clinical outcomes, we compared the findings of contrast-enhanced magnetic resonance imaging (CE-MRI) between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). In 168 patients undergoing early invasive intervention for STEMI (n = 113) and NSTEMI (n = 55), CE-MRI was performed a median of 6 days after the index event. Infarct size was measured on delayed-enhancement imaging, and area at risk (AAR) was quantified on T2-weighted images. The median infarct size was significantly smaller in the NSTEMI group than in the STEMI group (10.7% [5.6-18.1] vs. 19.2% [10.3-30.7], P < 0.001). Although there was a trend toward a greater myocardial salvage index ([AAR - infarct size] * 100/AAR) in the NSTEMI group compared to the STEMI group (48.2 [30.4-66.8] vs. 40.5 [24.8-53.5], P = 0.056), myocardial salvage index was similar between the groups in patients with anterior infarction (39.6 [20.0-54.9] vs. 35.5 [23.2-53.4], P = 0.96). The NSTEMI group also had a significantly lower extent of microvascular obstruction and a smaller number of segments with >75% of infarct transmurality relative to the STEMI group (0% [0-0.6] vs. 0.9% [0-2.3], P < 0.001 and 3.0 +/- 2.3 vs. 4.6 +/- 2.9, P = 0.001, respectively). Myocardial hemorrhage was detected less frequently in the NSTEMI group than the STEMI group (22.6% vs. 43.8%, P = 0.029). In the multivariate analysis, baseline Thrombolysis In Myocardial Infarction flow grade 3 and hemorrhagic infarction were closely associated with ST-segment elevation (OR 0.32, 95% CI 0.13-0.81, P = 0.017; OR 5.66, 95% CI 1.77-18.12, P = 0.003, respectively). In conclusion, in vivo pathophysiological differences revealed by CE-MRI assessment include more favorable infarct size, AAR, myocardial salvage and reperfusion injury in patients with NSTEMI compared to those with STEMI undergoing early invasive intervention. PMID- 22072244 TI - 18F-FDG PET/CT imaging of the pancreas: spectrum of diseases. AB - Since the introduction of integrated positron emission tomography-computed tomography (PET/CT), it has a great impact on the field of oncology. Comparing to other conventional scanners, only PET/CT is capable of providing important information on accurate detecting, staging/restaging, and post-therapeutic monitoring of many cancers. Many studies have demonstrated that PET/CT changes the management in approximately 30% of all cancer patients. Because 2-((18)F) fluoro-2-deoxy-D-glucose (FDG) is a nonspecific tracer, understanding the PET/CT limitations and pitfalls for various pancreatic conditions can lead to more accurate interpretation of PET/CT images, which ultimately would impact patient care. As a result, it is important for radiologists and other clinicians to familiarize themselves with a wide spectrum of pancreatic PET/CT findings simulating cancer from benign entities. PMID- 22072245 TI - Pancreatic peptides in young and elderly Zucker type 2 diabetic fatty rats. AB - CONTEXT: The global prevalence of diabetes mellitus, and in particular type 2 diabetes mellitus is increasing at an alarming rate. Risk factors for development of diabetes include obesity and advancing age. OBJECTIVES: The distribution of insulin, glucagon, somatostatin and pancreatic polypeptide in the pancreatic islets has been investigated in young and elderly type 2 Zucker diabetic fatty (ZDF) rats and age-matched Zucker lean (ZL) controls. METHODS: Experiments were performed in male animals aged either 9-13 weeks or 30-34 weeks. Immunohistochemistry was used to label insulin, glucagon, somatostatin and pancreatic polypeptide in islet cells. RESULTS: The percentage of insulin positive cells was unaltered in young but decreased in elderly ZDF (35.5 +/- 2.5%) rats compared to ZL controls (57.9 +/- 1.8%). The percentage of glucagon positive cells was increased in young ZDF (58.7 +/- 3.4%) compared to ZL controls (23.4 +/- 2.1%). However, in elderly rats the percentage of glucagon-positive cells declined in ZDF rats and was no longer different from ZL controls. The percentage of somatostatin-positive cells was unaltered in young and elderly ZDF rats compared to ZL controls. The percentage of pancreatic polypeptide-positive cells was unaltered in young but increased in elderly ZDF (22.0 +/- 2.5%) rats compared to ZL controls (13.8 +/- 1.8%). CONCLUSIONS: The distribution of pancreatic hormones is altered to varying extents in the ZDF rat and during the normal aging process. PMID- 22072246 TI - The use of nasojejunal nutrition in patients with chronic pancreatitis. AB - CONTEXT: Abdominal pain, malabsorption and diabetes all contribute to a negative impact upon nutritional status in chronic pancreatitis and no validated standard for the nutritional management of patients exists. OBJECTIVE: To assess the effect of nasojejunal nutrition in chronic pancreatitis patients. DESIGN: All consecutive chronic pancreatitis patients fed via the nasojejunal route between January 2004 and December 2007 were included in the study. Patients were assessed via retrospective review of case notes. RESULTS: Fifty-eight chronic pancreatitis patients (35 males, 23 females; median age 46 years) were included. Patients were discharged after a median of 14 days and nasojejunal nutrition continued for a median of 47 days. Forty-six patients (79.3%) reported resolution of their abdominal pain and cessation of opioid analgesia intake over the study period and median weight gain at 6 weeks following nutritional cessation was +1 kg (range 24 to +27 kg; P=0.454). Twelve (20.7%) patients reported recurrence of their pain during the follow-up period and complications were both minor and infrequent. Significant improvements were noted in most blood parameters measured, including: sodium (from 134.8 to 138.1 mEq/L; P<0.001); urea (from 3.4 to 5.1 mmol/L; P<0.001); creatinine (from 58.3 to 60.3 umol/L; P<0.001); corrected calcium (from 2.24 to 2.35 mmol/L; P=0.018); albumin (from 34.5 to 38.7 g/L; P=0.002); CRP (from 73.0 to 25.5 mg/L; P=0.006); and haemoglobin (from 11.8 to 12.4 g/dL; P=0.036). CONCLUSION: Nasojejunal nutrition, commenced in hospital and continued at home, is safe, efficacious and well tolerated in patients with severe chronic pancreatitis and is effective in helping to relieve pain and diminish analgesic requirements. PMID- 22072247 TI - Drug-induced acute pancreatitis in a cohort of 328 patients. A single-centre experience from Australia. AB - CONTEXT: Acute pancreatitis is associated with risk of morbidity and even mortality. Routine prescription drugs have been linked to the causation of acute pancreatitis. OBJECTIVE: To determine the incidence, presentation, course and outcome of drug-induced acute pancreatitis amongst patients admitted to a public hospital. DESIGN/SETTING: A retrospective analysis of patients presenting with acute pancreatitis to the Modbury Hospital, South Australia from January 2006 to April 2011. MAIN OUTCOME MEASURE: Each admission was reviewed within the electronic database for patient details as well as to determine the aetiological factor. In patients with drug-induced acute pancreatitis, the WHO Probability Scale was used to evaluate causality relationship. RESULTS: Three-hundreds and 28 patients were treated for acute pancreatitis during the study period. Biliary and alcohol-induced acute pancreatitis accounted for 80.8% of cases. Eleven patients (2 male and 9 female patients; median age: 59 years) were diagnosed with drug induced acute pancreatitis. These included 5 cases of codeine-, 2 cases of azathioprine-, and 1 case each of chlorothiazide-, valproic acid-, oestradiol- and simvastatin-induced acute pancreatitis. Nine patients had a mild disease while 2 patients had severe acute pancreatitis with a median hospital stay of 4 days. Withdrawal of the drug resulted in cessation of the attacks in all patients over a median follow-up of 24 months. CONCLUSIONS: Routine prescription drugs, as an aetiological factor, accounted for 3.4% of cases of acute pancreatitis. The disease appeared to be more common in middle-aged women. It is likely that the overall incidence of this entity is under-reported owing to the stringent criteria needed to conclusively determine a causal relationship. PMID- 22072248 TI - The impact of body mass index on pancreatic fistula after pancreaticoduodenectomy in Asian patients on the basis of Asia-Pacific perspective of body mass index. AB - CONTEXT: Several surgical complications are related to obesity. OBJECTIVE: This study evaluated the impact of obesity on pancreatic fistula after pancreaticoduodenectomy. DESIGN: We retrospectively reviewed the medical records of 159 patients who underwent pancreaticoduodenectomy between October 2002 and December 2008. SETTING: The patients were divided according to the body mass index as obese (body mass index equal to, or greater than, 25 kg/m(2)), or normal (body mass index less than 25 kg/m(2)). METHODS: Univariate and multivariate analyses were applied. Two-tailed P values less than 0.05 were considered as significant. RESULTS: Forty-six patients (28.9%) were obese and 113 patients (71.1%) were normal-weight. Obese group had a significantly higher incidence of pancreatic fistula and a greater amount of intraoperative blood loss. Other surgical complications were not significantly different between the two groups. Multivariate analysis found obesity, small pancreatic duct size (less than, or equal to, 3 mm), intraoperative blood loss, and combined resection as significant factors affecting pancreatic fistula. CONCLUSIONS: Obese patients have an increased risk for pancreatic fistula after pancreaticoduodenectomy. PMID- 22072249 TI - Acute recurrent pancreatitis: a possible clinical manifestation of ampullary cancer. AB - CONTEXT: Acute recurrent pancreatitis still poses diagnostic difficulties. The coexistence or moreover the causative relationship of carcinoma of the ampulla of Vater and acute recurrent pancreatitis is fairly rare. CASE REPORT: We present a case of carcinoma of the ampulla of Vater that presented with acute recurrent necrotizing pancreatitis complicated with pseudocysts. A diagnosis of malignancy in the ampulla was only made after several ERCP attempts due to residual inflammation at the periampullary area. CONCLUSION: Malignancy at the ampulla of Vater causing recurrent episodes of pancreatitis represents a realistic risk and attempts to diagnose the underlying cause should always take into account the possibility of cancer. PMID- 22072250 TI - Pancreatic carcinoma masquerading as groove pancreatitis: case report and review of literature. AB - CONTEXT: Groove pancreatitis is a distinct form of chronic pancreatitis affecting the space surrounded by the pancreatic head, duodenum and common bile duct. It is an uncommon pancreatic disease with challenging imaging diagnosis that can lead to surgical dilemmas. The purpose of this study is to report a case and review the current clinical, radiological and pathological characteristics of groove pancreatic carcinoma and groove pancreatitis. CASE REPORT: A 58-year-old man, with a history of alcohol excess, presented with a 4 month history of upper abdominal pain associated with weight loss and vomiting. Failed duodenal dilatation led to gastroenterostomy with biopsies showing chronic inflammation. Further presentation with jaundice and pancreatic groove mass led to a Whipple's pancreaticoduodenectomy. Histopathology report demonstrated cystic areas in both medial and lateral walls of his duodenum microscopically consistent with groove pancreatitis and a moderate to poorly differentiated adenocarcinoma. CONCLUSION: Several studies have been attempted to clarify the points of differentiation between carcinoma and pancreatitis in the groove area. This discrimination has been proved to be difficult; frequently the definitive diagnosis is only obtained after surgical intervention. This condition should be considered when making the differential diagnosis in pancreatic groove pathology and duodenal stenosis. PMID- 22072251 TI - Intrapancreatic accessory spleen: investigative dilemmas and role of EUS-guided FNA for diagnostic confirmation. AB - CONTEXT: We submit a case of intrapancreatic accessory spleen. CASE REPORT: A 33 year-old patient with history of dyspepsia underwent imaging studies suggestive of a neuroendocrine tumor. After referral to our institute, endoscopic ultrasound guided fine needle aspiration (EUS-FNA) confirmed diagnosis as intrapancreatic accessory spleen. DISCUSSION: An accessory spleen may develop from estranged mesenchymal cells due to fusion failure of the splenic anlage. The prevalence of an accessory spleen is 10-30% with 80% of them present at the splenic hilum and 17% in the pancreatic tail. Intrapancreatic accessory spleen is commonly misdiagnosed as a pancreatic tumor. Since, the differential diagnosis includes pancreatic neuroendocrine tumors, additional investigation with EUS-FNA should be considered when radiological diagnosis is not definitive. CONCLUSION: For diagnosis of intrapancreatic accessory spleen, radiographic imaging is useful, but lacks specificity without tissue diagnosis. Diagnosis can be safely and reliably established with EUS-FNA, leading to a benign prognosis and avoidance of unnecessary surgical intervention. PMID- 22072252 TI - Ectopic pancreas presenting as periampullary tumor with obstructive jaundice and pruritus is a rare diagnostic and therapeutic dilemma. A case report. AB - CONTEXT: Ectopic pancreatic rest is an uncommon condition resulting in diverse clinical and pathological presentation. It results from altered development of two primitive pancreatic buds that fuse to form the uncinate-head and body-tail of normal gland. Ectopic pancreas is an anomaly where an ectopic rest develops at a place away from the normal site. CASE REPORT: We describe a 48-year-old male patient who presented with progressive jaundice and pruritus. He was established to have a periampullary mass highly suggestive of malignancy, for which he undergo pancreaticoduodenectomy. However, histology showed ectopic pancreatic tissue in the periampullary region. CONCLUSION: This case highlights importance of preoperative histological diagnosis of periampullary tumors to avoid morbid surgical procedure in the form pancreaticoduodenectomy. Ectopic pancreas should include differential diagnosis of periampullary tumors. PMID- 22072253 TI - EUS-guided antegrade transhepatic placement of a self-expandable metal stent in hepatico-jejunal anastomosis. AB - CONTEXT: To demonstrate an EUS-guided biliary drainage in patient with gastrointestinal tract modified surgically. CASE REPORT: An EUS guided access to the left intra hepatic duct, followed by an antegrade passage of a partially self expandable metal stent that was removed by using an enteroscope, in one patient with hepatico-jejunal anastomosis. There were no early or delayed complications and the procedure was effective in relieving jaundice until the self-expandable metal stent was removed, 3 months later. A cholangiogram was obtained via enteroscopy, after removal of self-expandable metal stent, and found to be normal. The patient had an uneventful evaluation afterwards. CONCLUSION: The indication of these procedures must be made under a multidisciplinary view while sharing information with the patient or legal guardian. EUS-guided biliary drainage is feasible when performed by professionals with expertise in biliopancreatic endoscopy and advanced echo-endoscopy and should be performed currently under rigorous protocol in educational institutions. PMID- 22072254 TI - Lack of an association between autoimmune pancreatitis and Varicella Zoster Virus. PMID- 22072255 TI - Total pancreatectomy and quality of life. PMID- 22072256 TI - A one-pot catalysis: the strategic classification with some recent examples. AB - In this "Emerging Area", the strategic classification of one-pot catalysis, i.e. cooperative, relay and sequential catalysis, is described. In order to illustrate this classification, we take the readers through a series of recent examples which utilize either metal-metal, metal-organo and organo-organo catalysts. The compilation clearly demonstrates the explosive growth and power of this field, which has become, in the last few years, an important technique particularly in the case of enantioselective catalysis. PMID- 22072257 TI - Association between endolymphatic hydrops as revealed by magnetic resonance imaging and caloric response. AB - OBJECTIVE: To investigate the association between the degree of endolymphatic hydrops (EH) revealed by magnetic resonance imaging (MRI) and a caloric response in the ear. STUDY DESIGN: Prospective diagnostic study. SETTING: University hospital. PATIENTS: Twenty-four patients with hearing loss and/or vertigo, who underwent MRI 1 day after an intratympanic gadolinium injection. INTERVENTION: MRI after intratympanic gadolinium injection and caloric testing with cool air stimulation (15 degrees C, 6 l/min, 60 s). MAIN OUTCOME MEASURE: Association between the degree of EH and caloric responses. The degree of EH in the vestibule, in the cochlea, and in the ampulla of the lateral semicircular canal (LSC) was evaluated using MRI. The ratio of the diameter of the endolymphatic space to the diameter of the perilymphatic space was measured in the LSC ampulla. RESULTS: Canal paresis (CP, >25%) was present in 15 patients and absent (CP, <25%) in 9 patients. There was no significant difference between caloric response and the degree of EH in the vestibule, the cochlea, or the LSC ampulla. The period between the onset of clinical symptoms and examination tended to be longer in the group with CP compared with the group without CP. CONCLUSION: There was no significant association between the degree of EH and caloric response. PMID- 22072258 TI - Preoperative embolization of the inferior petrosal sinus in surgery for glomus jugulare tumors. AB - OBJECTIVE: To compare the outcomes of surgery for glomus tumors involving the jugular foramen with and without preoperative venous embolization of the inferior petrosal sinus (IPS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Twenty-four patients with paragangliomas involving the jugular foramen treated between 1995 and 2008. INTERVENTION: All patients underwent surgical resection after receiving preoperative angioembolization with or without venous embolization of the IPS. MAIN OUTCOME MEASURES: Total operative duration, estimated blood loss, intensive care unit and total hospital days, and novel postoperative lower cranial nerve deficits were recorded, and appropriate statistical analysis was conducted. RESULTS: Twenty-four patients met inclusion criteria. Fourteen of these patients underwent preoperative embolization of the IPS in addition to angioembolization. The group that did not undergo embolization of the IPS was used as the control group (n = 10). These groups were compared with regard to the above outcome measures. Blood loss and new lower cranial nerve deficits were reduced in the venous embolization group, although neither measure reached statistical significance. Tumor size correlated with increased intraoperative hypotensive events and longer total hospital stay, and these correlations were statistically significant. CONCLUSION: Preoperative embolization of the IPS is possible in many patients undergoing surgery of the jugular foramen. The addition of venous embolization to the traditional arterial embolization of glomus jugulare tumors adds little additional time or expense to the procedure and facilitates control of bleeding once the jugular bulb has been opened. PMID- 22072259 TI - Experience with vibroplasty couplers at the stapes head and footplate. AB - OBJECTIVE: To report on experiences with implanting the Vibrant Soundbridge (VSB) coupled to the stapes head using a new Clip-Coupler or to the stapes footplate using a new OW-Coupler (CliP- or OW-Coupler Vibroplasty). STUDY DESIGN: Single subject, repeated measures. SETTING: Two university hospital ENT departments. PATIENTS: Fourteen German-speaking patients from 2 European study sites were implanted with either a CliP-Coupler or OW-Coupler attached to a VSB floating mass transducer (FMT). They were evaluated preoperatively and postoperatively for bone and air conduction thresholds with and without the implant, as well as speech perception tests. MAIN OUTCOME MEASURES: Measuring the efficacy and safety of OW- and CliP-Coupler-Vibroplasty as a method to treat mixed hearing loss. RESULTS: Bone conduction thresholds remained stable preoperatively and postoperatively. The patients' average speech perception performances at 65/80 dB (HL) increased from 0.8/13.8% to 63/82%. The pure tone audiograms showed an average improvement in air conduction thresholds after implantation with the VSB of 25 dB at 0.5 kHz to 50 dB at 4 kHz. CONCLUSION: OW- or Clip-Coupler Vibroplasty using couplers was found to be a straightforward procedure, which produced good results in this group of patients. PMID- 22072260 TI - Surgical trauma after sequential insertion of intracochlear catheters and electrode arrays (a histologic study). AB - HYPOTHESIS: To evaluate histologically the risk of trauma to intracochlear structures after sequential insertion of an intracochlear catheter and an electrode array. BACKGROUND: A previous computed tomographic scan-based study demonstrated that introduction of a flexible disposable intracochlear catheter for drug delivery to a distance of up to 15 mm was feasible and showed no radiologic evidence of basilar membrane trauma. METHODS: Fifteen fresh human temporal bones were prepared for cochlear implantation. We sequentially performed the introduction of the catheter, the injection of 15 ul of an iodine solution into the scala tympani via the catheter, and the removal of the catheter in 14 temporal bones, and finally, 2 types of electrode array (Flex EAS and Flex Soft) from MED-EL, were inserted into 10 temporal bones. The bones were fixed and embedded in methylmethacrylate to cut the undecalcified temporal bones parallel to the modiolus axis with the electrode array in place, and each histologic section was photographed to document the location and extent of trauma in the cochlea. RESULTS: No specific damage (Grade 0 trauma) to cochlear structures occurred in 12 temporal bones, and elevation of basilar membrane (Grade 1 trauma) occurred in 2 cases. The electrode array was positioned in the scala tympani under the basilar membrane in all temporal bones, with one exception, in which the Flex Soft electrode array deviated behind the spiral ligament and into the scala vestibuli apically (Grade 3 trauma). CONCLUSION: The infusion of an iodine solution within an intracochlear catheter and the subsequent insertion of an electrode array was shown to be feasible and often atraumatic. PMID- 22072261 TI - Accuracy of computed tomography detection of superior canal dehiscence. AB - HYPOTHESIS: High-resolution temporal bone computed tomography (CT) may erroneously demonstrate a superior semicircular canal dehiscence (SSCD) where none exists and inaccurately display the size of a dehiscence. BACKGROUND: CT is an integral component of the diagnosis of SSCD. The prevalence of dehiscence as measured on computed tomographic scan is approximately eightfold higher than that on histologic studies, suggesting that CT may have a relatively low specificity for identifying canal dehiscence. This, in turn, can lead to an inappropriate diagnosis and treatment plan. METHODS: We quantified the accuracy of CT in identifying a dehiscence of the superior semicircular canal in a cadaver model using microCT as a gold standard. The superior canals of 11 cadaver heads were blue lined. Twelve of the 22 ears were further drilled to create fenestrations of varying sizes. Heads were imaged using medical CT, followed by microCT scans of the temporal bones at 18-um resolution. Diagnosis of dehiscence and measurements of dehiscence size were performed on clinical CT and compared with that of microCT. RESULTS: Clinical CT identified 7 of 8 intact canals as dehiscent and tended to overestimate the size of smaller fenestrations, particularly those surrounded by thin bone. CONCLUSION: These findings confirm that medical CT cannot be used as the exclusive gold standard for SSCD and that, particularly for small dehiscences on CT, clinical symptoms must be clearly indicative of a dehiscence before surgical treatment is undertaken. Preoperative counseling for small dehiscences may need to include the possibility that no dehiscence may be found despite radiologic evidence for it. PMID- 22072262 TI - Response to "Simultaneous true stapes fixation and bilateral bony dehiscence between the internal carotid artery and the apex of the cochlea: the ultimate pitfall". PMID- 22072263 TI - Electrocochleography as a diagnostic and intraoperative adjunct in superior semicircular canal dehiscence syndrome. AB - OBJECTIVE: To determine the electrocochleographic characteristics of ears with superior semicircular canal dehiscence (SSCD) and to examine its use for intraoperative monitoring in canal occlusion procedures. STUDY DESIGN: Case series. SETTING: Academic medical center. PATIENTS: Thirty-three patients (45 ears) had clinical and computed tomographic evidence of SSCD; 8 patients underwent intraoperative electrocochleography (ECoG) during superior canal occlusion; 9 patients underwent postoperative ECoG after SSCD occlusion. INTERVENTIONS: Diagnostic, intraoperative, and postoperative extratympanic ECoG; middle fossa or transmastoid occlusion of the superior semicircular canal. MAIN OUTCOME MEASURE: Summating potential (SP) to action potential (AP) ratio, as measured by ECoG, and alterations in SP/AP during canal exposure and occlusion. RESULTS: Using computed tomography as the standard, elevation of SP/AP on ECoG demonstrated 89% sensitivity and 70% specificity for SSCD. The mean SP/AP ratio among ears with SSCD was significantly higher than that among unaffected ears (0.62 versus 0.29, p < 0.0001). During occlusion procedures, SP/AP increased on exposure of the canal lumen (mean change +/- standard deviation, 0.48 +/- 0.30). After occlusion, SP/AP dropped below the intraoperative baseline in most cases (mean change, -0.23 +/- 0.52). All patients experienced symptomatic improvement. All patients who underwent postoperative ECoG 1 to 3 months after SSCD repair maintained SP/AP of 0.4 or lesser. CONCLUSION: These findings expand the differential diagnosis of abnormal ECoG. In conjunction with clinical findings, ECoG may support a clinical diagnosis of SSCD. Intraoperative ECoG facilitates dehiscence documentation and allows the surgeon to confirm satisfactory canal occlusion. PMID- 22072264 TI - Profound high-frequency sensorineural hearing loss treatment with a totally implantable hearing system. AB - OBJECTIVE: This study seeks to assess the efficacy of the Envoy Esteem totally implantable hearing device in treating profound high-frequency sensorineural hearing loss. PATIENTS: Five patients with profound high-frequency hearing loss participating in a prospective, multi-center, nonrandomized Food and Drug Administration clinical trial. INTERVENTION: Implantation with Esteem totally implantable hearing device and comparison to baseline unaided and aided conditions. MAIN OUTCOME MEASURE: Speech reception threshold and word recognition scores (WRS) at 50 dB HL presentation level. RESULTS: Preoperative speech reception threshold improved from an unaided 65 dB and aided 48 dB average to 26 dB with the Esteem at 12 months. WRS at 50 dB scores improved from an unaided 10% and aided 23% average to 78% postoperatively. CONCLUSION: The Esteem totally implantable middle ear hearing device provides appreciable functional gain and improvement in WRS to rehabilitate hearing in patients with a profound high frequency sensorineural hearing loss. PMID- 22072265 TI - Histopathologic markers of hearing loss in intralabyrinthine schwannomas: implications for management. AB - OBJECTIVE: This study aimed to review the clinical history and management of patients with intralabyrinthine schwannomas and evaluate the histopathologic features of these tumors. STUDY DESIGN: A retrospective case review of 24 patients and 7 temporal bone specimens. SETTING: An otologic tertiary referral private practice. PATIENTS: Patients with magnetic resonance imaging-confirmed intralabyrinthine schwannoma diagnosed after 1995 and non-Neurofibromatosis type 2 temporal bone specimens with schwannomas confined to the bony labyrinth. MAIN OUTCOME MEASURES: Clinical data including history, imaging and audiometry were evaluated. The histopathologic features of temporal bone specimens including tumor location and degenerative changes were analyzed. RESULTS: The intralabyrinthine location of the tumor does not predict the degree or time to progression of hearing loss. Both sensorineural and conductive hearing loss can occur. Mechanisms of hearing loss include hair cell, spiral ganglion, and stria vascularis degeneration in addition to mechanical obstruction. CONCLUSION: Hearing loss is the most common symptom with intralabyrinthine schwannomas. Histopathology reveals that multiple mechanisms of degeneration may occur within the labyrinth to induce hearing loss. Observation provides the most reliable hearing preservation strategy. PMID- 22072266 TI - Keyhole cochlear implantation: current status. AB - INTRODUCTION: Past cochlear implantation (CI) techniques have included a variety of soft tissue and bony trauma to place and stabilize the implant body. Despite minimalist approaches, the surgery invites further refinement. MATERIALS AND METHODS: A restricted access "keyhole" CI technique was developed through a series of 547 cases undertaken from 1997. The surgery used a 20-mm-diameter mini C-incision on the rear of the auricle and avoided the use of a bony retention well or suture fixation. Initial body migration rates were successfully countered using small titanium mesh "bridges." The series was free from other problems specific to the technique. DISCUSSION: The study demonstrates that CI can be performed with only restricted exposure, disposing of well and suture fixation methods, and without a wound that may be adjacent to the implant body or electrode arrays. CONCLUSION: The keyhole approach proved atraumatic and brief. It is particularly suited to simultaneous bilateral implantation in the infant and proved adaptable to all ages. PMID- 22072267 TI - Changes in Listing plane thickness caused by vestibular schwannoma: a parameter for evaluating the accuracy of the gravity-oriented internal model. AB - OBJECTIVE: Three-dimensional analysis of video-oculograms can be used to calculate Listing plane for patients and experimental subjects. Listing plane reflects the head's orientation with respect to gravity, which suggests that the plane is derived from otolithic vestibular input, itself, or from a gravity oriented internal model constructed through integration of visual, vestibular, and proprioceptive sensory inputs. The goal of this study was to determine whether the Listing plane can serve as a parameter for evaluating static (peripheral or central) vestibular function. STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Healthy subjects and patients with unilateral vestibular schwannoma without any previous treatment. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Video-oculograms were recorded from healthy subjects (aged 36.8 +/- 6.3 yr) and from patients (aged 60.3 +/- 7.5 yr) during voluntary gaze with the head in an upright or each-side-down orientation, and the thicknesses of the calculated Listing planes were then compared. RESULTS: Results revealed thickening of the Listing plane in patients only when the head was in an impaired-side-down orientation (1.250 +/- 0.795 and 1.074 +/- 0.759 degrees in the right- and left-side-down head orientations in healthy subjects versus 2.222 +/- 1.237 degrees in the impaired-side-down orientation in patients), and this thickening correlated with caloric weakness. By contrast, neither the sensation of postural instability nor postural disturbance in force platform recordings contributed to the thickness of Listing plane. CONCLUSION: The thickness of the Listing plane could be a novel parameter for quantitatively evaluating static vestibular (otolithic) function, although central compensation might exist. PMID- 22072268 TI - The controversial beginnings of neurotology: William F. House's struggles as a medical innovator. PMID- 22072269 TI - Misdiagnosis of acute peripheral vestibulopathy in central nervous ischemic infarction. AB - INTRODUCTION: Vertigo is a very common symptom at otorhinolaryngology (ENT), neurological, and emergency units, but often, it is difficult to distinguish between vertigo of peripheral and central origin. PATIENTS AND METHODS: We conducted a retrospective analysis of a hospital database, including all patients admitted to the ENT University Hospital Graz after neurological examination, with a diagnosis of peripheral vestibular vertigo and subsequent diagnosis of central nervous infarction as the actual cause for the vertigo. Twelve patients were included in this study. RESULTS: All patients with acute spinning vertigo after a thorough neurological examination and with uneventful computed tomographic scans were referred to our ENT department. Nine of them presented with horizontal nystagmus. Only 1 woman experienced additional hearing loss. The mean diagnostic delay to the definite diagnosis of a central infarction through magnetic resonance imaging was 4 days (SD, 2.3 d). CONCLUSION: A careful otologic and neurological examination, including the head impulse test and caloric testing, is mandatory. Because ischemic events cannot be diagnosed in computed tomographic scans at an early stage, we strongly recommend to perform cranial magnetic resonance imaging within 48 hours from admission if vertigo has not improved under conservative treatment. PMID- 22072270 TI - Genome-wide association study identifies 5q21 and 9p24.1 (KDM4C) loci associated with alcohol withdrawal symptoms. AB - Several genome-wide association (GWA) studies of alcohol dependence (AD) and alcohol-related phenotypes have been conducted; however, little is known about genetic variants influencing alcohol withdrawal symptoms (AWS). We conducted the first GWA study of AWS using 461 cases of AD with AWS and 408 controls in Caucasian population in the Collaborative Study on the Genetics of Alcoholism (COGA) sample. Logistic regression analysis of AWS as a binary trait, adjusted for age and sex, was performed using PLINK. We identified 51 SNPs associated with AWS with p < 10(-4). The first best signal was rs770182 (p = 3.65 * 10(-6)) at 5q21 near EFNA5 gene which was replicated in the Australian twin-family study of 273 families (p = 0.0172). Furthermore, three SNPs (rs10975990, rs10758821 and rs1407862) within KDM4C gene at 9p24.1 showed p < 10(-4) (p = 7.15 * 10(-6), 2.79 * 10(-5) and 4.93 * 10(-5), respectively) in the COGA sample while one SNP rs12001158 within KDM4C with p = 1.97 * 10(-4) in the COGA sample was replicated in the family sample (p = 0.01). Haplotype analysis further supported the associations of single-marker analyses of KDM4C in the COGA sample. Moreover, two SNPs (rs2046593 and rs10497668) near FSIP2 at 2q32.1 with moderate associations with AWS in the COGA sample (p = 2.66 * 10(-4) and 9.48 * 10(-5), respectively) were replicated in the family sample (p = 0.0013 and 0.0162, respectively). In addition, several SNPs in GABRA1, GABRG1, and GABRG3 were associated with AWS (p < 10(-2)) in the COGA sample. In conclusion, we identified several loci associated with AWS. These findings offer the potential for new insights into the pathogenesis of AD and AWS. PMID- 22072271 TI - Follicular-patterned tumors of the thyroid: the battle of benign vs. malignant vs. so-called uncertain. AB - This article will review the controversial area of follicular-patterned thyroid tumors. The literature is discussed with emphasis on pathologic diagnosis and the criteria for malignancy. In addition, the current state of knowledge regarding molecular markers and their utility in diagnosing benign from malignant nodules is described. Finally, the apparent lack of consistency with regard to results of certain immunohistochemical markers is included. PMID- 22072272 TI - Randomized controlled trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma. AB - BACKGROUND: Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients, and available treatments are of little benefit. The objective of this trial was to determine whether acupuncture can prevent xerostomia among head/neck patients undergoing radiotherapy. METHODS: A randomized, controlled trial among patients with nasopharyngeal carcinoma was conducted comparing acupuncture to standard care. Participants were treated at Fudan University Shanghai Cancer Center, Shanghai, China. Forty patients were randomized to acupuncture treatment and 46 to standard care. Patients were treated 3*/wk on the same days they received radiotherapy. Subjective measures included the Xerostomia Questionnaire and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN). Objective measures were unstimulated and stimulated whole salivary flow rates. Patients were followed for 6 months after the end of radiotherapy. RESULTS: Xerostomia Questionnaire scores for acupuncture were statistically significantly lower than for controls starting in week 3 through the 6 months (P = .003 at week 3, all other P < .0001), with clinically significant differences as follows: week 11, relative risk (RR) 0.63 (95% confidence interval [CI], 0.45-0.87); 6 months, RR 0.38 (95% CI, 0.19-0.76). Similar findings were seen for MDASI-HN scores. Group differences emerged as early as 3 weeks into treatment for saliva (unstimulated whole salivary flow rate, P = .0004), with greater saliva flow in the acupuncture group at week 7 (unstimulated whole salivary flow rate, P < .0001; stimulated whole salivary flow rate, P = .002) and 11 (unstimulated whole salivary flow rate, P < .02; stimulated whole salivary flow rate, P < .03) and at 6 months (stimulated whole salivary flow rate, P < .003). CONCLUSIONS: Acupuncture given concurrently with radiotherapy significantly reduced xerostomia and improved quality of life. PMID- 22072273 TI - Mass size distribution and chemical composition of the surface layer of summer and winter airborne particles in Zabrze, Poland. AB - Mass size distributions of ambient aerosol were measured in Zabrze, a heavily industrialized city of Poland, during a summer and a winter season. The chemical analyses of the surface layer of PM(10), PM(2.5) and PM(1) in this area were also performed by X-ray photoelectron spectroscopy (XPS). Results suggested that the influence of an atmospheric aerosol on the health condition of Zabrze residents can be distinctly stronger in winter than in summer because of both: higher concentration level of particulate matter (PM) and higher contribution of fine particles in winter season compared to summer. In Zabrze in June (summer) PM(10) and PM(2.5) reached about 20 and 14 MUg/m(3), respectively, while in December (winter) 57 and 51 MUg/m(3), respectively. The XPS analysis showed that elemental carbon is the major surface component of studied airborne particles representing about 78%-80% (atomic mass) of all detected elements. PMID- 22072274 TI - Comparative and evolutionary analysis of new variants of omega-gliadin genes from three A-genome diploid wheats. AB - A genomic polymerase chain reaction (PCR) cloning strategy was applied to isolate omega-gliadin sequences from three A-genome diploid wheats (Triticum monococcum, T. boeoticum and T. urartu). Amplicon lengths varied from 744 and 1,044 bp, and those of the corresponding deduced mature proteins from 248 to 348 residues. The primary structure of the deduced polypeptides comprised a short N- and C-terminal conserved domain, and a long, variable repetitive domain. A phylogenetic analysis recognised several clades: the first consisted of three T. aestivum sequences; the second and the third two T. boeoticum and six T. monococcum sequences; and the rest four T. urartu and three T. aestivum sequences. Among the functional (non-pseudogene) ARQ/E-type omega-gliadin sequences, two were derived from T. boeoticum and three from T. monococcum; one of the latter sequences appeared to be a chimera originating via illegitimate recombination between the other two T. monococcum sequences. None of the 12 intact omega-gliadin sequences contained any cysteine or methionine residues. We discussed the variation and evolution of A genome omega-gliadin genes. PMID- 22072275 TI - Genetics of migraine in the age of genome-wide association studies. AB - Genetic factors importantly contribute to migraine. However, unlike for rare monogenic forms of migraine, approaches to identify genes for common forms of migraine have been of limited success. Candidate gene association studies were often negative and positive results were often not replicated or replication failed. Further, the significance of positive results from linkage studies remains unclear owing to the inability to pinpoint the genes under the peaks that may be involved in migraine. Problems hampering these studies include limited sample sizes, methods of migraine ascertainment, and the heterogeneous clinical phenotype. Three genome-wide association studies are available now and have successfully identified four new genetic variants associated with migraine. One new variant (rs1835740) modulates glutamate homeostasis, thus integrates well with current concepts of neurotransmitter disturbances. This variant may be more specific for severe forms of migraine such as migraine with aura than migraine without aura. Another variant (rs11172113) implicates the lipoprotein receptor LRP1, which may interact with neuronal glutamate receptors, thus also providing a link to the glutamate pathway. In contrast, rs10166942 is in close proximity to TRPM8, which codes for a cold and pain sensor. For the first time this links a gene explicitly implicated in pain related pathways to migraine. The potential function of the fourth variant rs2651899 (PRDM16) in migraine is unclear. All these variants only confer a small to moderate change in risk for migraine, which concurs with migraine being a heterogeneous disorder. Ongoing large international collaborations will likely identify additional gene variants for migraine. PMID- 22072276 TI - The development of fear learning and generalization in 8-13 year-olds. AB - The current study examined developmental changes in fear learning and generalization in 40 healthy 8-13 year-olds using an aversive conditioning paradigm adapted from Lau et al. [Lau et al. [2008] Journal of the American Academy of Child and Adolescent Psychiatry 47:94-102]. In this task, the conditioned stimuli (CS+/CS-) are two neutral female faces, and the unconditioned stimulus is a fearful, screaming face. The second phase of the study also included a generalization stimulus (GS): a 50% blend of the CS+/- faces. The eye blink startle reflex was utilized to measure defensive responding. Patterns of fear learning and generalization were qualified by child age. Older children demonstrated greater fear learning (i.e., larger startle during CS+ than CS-) than younger children. In addition, older children exhibited the typical pattern of generalization observed in adults, whereas younger children did not. Finally, fear learning also related to contingency awareness; only children who correctly identified the CS+ demonstrated fear-potentiated startle to the CS+. Clinical implications and future directions are discussed. PMID- 22072277 TI - A simulation study to improve performance in the preparation and delivery of antineoplastic medications at a community hospital. AB - In this paper, we introduce a simulation study to improve the antineoplastic medication preparation and delivery performance at a pharmacy department in a large community hospital. The goal of this work is to help pharmacy reduce patients' average waiting time when receiving chemotherapy. This will be achieved by simulating and analyzing the preparation and delivery procedures to identify process bottlenecks, carry out what-if analysis, predict the impact of improvement effort, and provide recommendations to hospital leadership. Using the simulation model, we discover that by introducing early preparation for the returning patients and dedicating an infusion staff member for medication delivery, patients' waiting time for antineoplastic medications can be reduced substantially. Such improvements do not require additional floor space or significant investment. The recommendation has been accepted by hospital management and implemented in the pharmacy department. The preliminary results have verified the simulation output with the desired improvement predicted by the model. PMID- 22072278 TI - Deployment of RFID in healthcare facilities-experimental design in MRI department. AB - Patient safety has become an important issue due to medical errors. Some health care systems use Radio Frequency Identification (RFID) to identify patients during medical procedures. However, the RFID data readability especially depends upon the environment, an investigation of data reliability and signal loss is essential to making an effective deployment plan. The operation of Magnetic Resonance Imaging (MRI) is the major source of electromagnetic interference in the hospital. Therefore, this research conducts an experimental design of reading performance considering various notable factors in the MRI department. In addition to the readability experiment, this paper also measures the efficiency and reliability of implementing RFID technology in the MRI department using a simulation approach and helps hospitals by providing the measured outcomes. PMID- 22072279 TI - Use and satisfaction with electronic health record by primary care physicians in a health district in Brazil. AB - It is believed that Electronic Health Records (EHR) improve not only quality of care but also patient safety and health care savings. This seems to be true for developed countries but not necessarily in emerging economies. This paper examined the primary care physicians' satisfaction with a specific EHR in a health district of a major city in Brazil and describes how they are using it as well as its specific functions. A cross-sectional questionnaire survey with all physicians from all Community Health Centers of the 6th health district of the City of Fortaleza that were using HER was conducted. From the 111 subjects (100%), a total of 99 physicians answered the survey (89% response rate). For overall satisfaction with the EHR, 2 (2%) were satisfied, 50 (50.5%) were satisfied in part and 47 (47.5%) were not satisfied. For the functionalities, a proportion of correct answers (PCA) and an index of functionality usage (IFU) were developed. PCA and IFU were significantly correlated (p < 0.001). Inverse and weak correlations were found between PCA and age (p < 0.001), years since medical school and years of work (p < 0.01). For usage (IFU), there was inverse correlation with "years working in Family Health Strategy" (p < 0.05). High IFU was associated with physicians who stated to use easily Internet and Email; who saw less patients per half-day; who were women (p < 0.05), younger (p < 0.05), in training (p < 0.05) and not satisfied with the EHR (p < 0.05).The use of EHR was associated with being young, female, still in training and seeing less than 16 patients per half-day. Structural issues (e.g. network and system support) seemed to be major barriers in this setting. Lack of classical functionalities such as problem list and clinical reminders could have contributed to exacerbate misperceptions about what EHRs can do in improving work processes and patient care. PMID- 22072280 TI - Automated classification of liver disorders using ultrasound images. AB - This paper presents a novel approach for detection of Fatty liver disease (FLD) and Heterogeneous liver using textural analysis of liver ultrasound images. The proposed system is able to automatically assign a representative region of interest (ROI) in a liver ultrasound which is subsequently used for diagnosis. This ROI is analyzed using Wavelet Packet Transform (WPT) and a number of statistical features are obtained. A multi-class linear support vector machine (SVM) is then used for classification. The proposed system gives an overall accuracy of ~95% which clearly illustrates the efficacy of the system. PMID- 22072281 TI - Adaptive significance of permanent female mimicry in a bird of prey. AB - Permanent female mimicry, in which adult males express a female phenotype, is known only from two bird species. A likely benefit of female mimicry is reduced intrasexual competition, allowing female-like males to access breeding resources while avoiding costly fights with typical territorial males. We tested this hypothesis in a population of marsh harriers Circus aeruginosus in which approximately 40 per cent of sexually mature males exhibit a permanent, i.e. lifelong, female plumage phenotype. Using simulated territorial intrusions, we measured aggressive responses of breeding males towards conspecific decoys of females, female-like males and typical males. We show that aggressive responses varied with both the type of decoys and the type of defending male. Typical males were aggressive towards typical male decoys more than they were towards female like male decoys; female-like male decoys were attacked at a rate similar to that of female decoys. By contrast, female-like males tolerated male decoys (both typical and female-like) and directed their aggression towards female decoys. Thus, agonistic responses were intrasexual in typical males but intersexual in female-like males, indicating that the latter not only look like females but also behave like them when defending breeding resources. When intrasexual aggression is high, permanent female mimicry is arguably adaptive and could be seen as a permanent 'non-aggression pact' with other males. PMID- 22072282 TI - Taylor's Law holds in experimental bacterial populations but competition does not influence the slope. AB - Populations vary in time and in space, and temporal variation may differ from spatial variation. Yet, in the past half century, field data have confirmed both the temporal and spatial forms of Taylor's power Law, a linear relationship between log(variance) and log(mean) of population size. Recent theory predicted that competitive species interactions should reduce the slope of the temporal version of Taylor's Law. We tested whether this prediction applied to the spatial version of Taylor's Law using simple, well-controlled laboratory populations of two species of bacteria that were cultured either separately or together for 24 h in media of widely varying nutrient richness. Experimentally, the spatial form of Taylor's Law with a slope of 2 held for these simple bacterial communities, but competitive interactions between the two species did not reduce the spatial Taylor's Law slope. These results contribute to the widespread usefulness of Taylor's Law in population ecology, epidemiology and pest control. PMID- 22072283 TI - A minute fossil phoretic mite recovered by phase-contrast X-ray computed tomography. AB - High-resolution phase-contrast X-ray computed tomography (CT) reveals the phoretic deutonymph of a fossil astigmatid mite (Acariformes: Astigmata) attached to a spider's carapace (Araneae: Dysderidae) in Eocene (44-49 Myr ago) Baltic amber. Details of appendages and a sucker plate were resolved, and the resulting three-dimensional model demonstrates the potential of tomography to recover morphological characters of systematic significance from even the tiniest amber inclusions without the need for a synchrotron. Astigmatids have an extremely sparse palaeontological record. We confirm one of the few convincing fossils, potentially the oldest record of Histiostomatidae. At 176 um long, we believe this to be the smallest arthropod in amber to be CT-scanned as a complete body fossil, extending the boundaries for what can be recovered using this technique. We also demonstrate a minimum age for the evolution of phoretic behaviour among their deutonymphs, an ecological trait used by extant species to disperse into favourable environments. The occurrence of the fossil on a spider is noteworthy, as modern histiostomatids tend to favour other arthropods as carriers. PMID- 22072284 TI - Plasticity of preferred body temperatures as means of coping with climate change? AB - Thermoregulatory behaviour represents an important component of ectotherm non genetic adaptive capacity that mitigates the impact of ongoing climate change. The buffering role of behavioural thermoregulation has been attributed solely to the ability to maintain near optimal body temperature for sufficiently extended periods under altered thermal conditions. The widespread occurrence of plastic modification of target temperatures that an ectotherm aims to achieve (preferred body temperatures) has been largely overlooked. I argue that plasticity of target temperatures may significantly contribute to an ectotherm's adaptive capacity. Its contribution to population persistence depends on both the effectiveness of acute thermoregulatory adjustments (reactivity) in buffering selection pressures in a changing thermal environment, and the total costs of thermoregulation (i.e. reactivity and plasticity) in a given environment. The direction and magnitude of plastic shifts in preferred body temperatures can be incorporated into mechanistic models, to improve predictions of the impact of global climate change on ectotherm populations. PMID- 22072285 TI - The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis. AB - PURPOSE: We aimed to assess the impact of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis. METHODS: An international expert panel determined diagnoses and clinical management in patients with suspected large vessel vasculitis, with and without the results of (18)F-FDG PET, respectively. The accuracy of the clinical diagnosis and the resulting clinical management with and without the (18)F-FDG PET results were compared using logistic regression models. RESULTS: The analysis included 30 patients referred to a tertiary care centre with large vessel vasculitis and 31 controls. (18)F-FDG PET had an overall sensitivity of 73.3% [95% confidence interval (CI) 54.1-87.7%], a specificity of 83.9% (95% CI 66.3-94.5%), a positive predictive value of 81.5% (95% CI 61.9-93.7%) and a negative predictive value of 76.5% (95% CI 58.8-89.3%). The diagnostic accuracy of (18)F-FDG PET was higher in patients not receiving immunosuppressive drugs (93.3 vs 64.5%, p = 0.006). Taken in context with other available diagnostic modalities, the addition of (18)F-FDG PET increased the clinical diagnostic accuracy from 54.1 to 70.5% (p = 0.04). The addition of (18)F-FDG PET increased the number of indicated biopsies from 22 of 61 patients (36.1%) to 25 of 61 patients (41.0%) and changed the treatment recommendation in 8 of 30 patients (26.7%) not receiving immunosuppressive medication and in 7 of 31 patients (22.6%) receiving immunosuppressive medication. CONCLUSION: (18)F-FDG PET is a sensitive and specific imaging tool for large vessel vasculitis, especially when performed in patients not receiving immunosuppressive drugs. It increases the overall diagnostic accuracy and has an impact on the clinical management in a significant proportion of patients. PMID- 22072286 TI - Measurement of SUVmax plus ADCmin of the primary tumour is a predictor of prognosis in patients with cervical cancer. AB - PURPOSE: The objectives of this study were to determine if measurements of the maximum standardized uptake value (SUVmax) by positron emission tomography/computed tomography and minimum apparent diffusion coefficient (ADCmin) by magnetic resonance imaging are correlated with the clinical characteristics and prognosis of primary cervical cancer. METHODS: The correlations between biological parameters and prognosis and SUVmax and ADCmin of the primary tumour were determined in 66 patients with cervical cancer before radiotherapy or concurrent chemoradiotherapy. RESULTS: There were significant correlations between SUVmax of the primary tumour and FIGO stage (p = 0.036), tumour maximum size (p = 0.018) and pelvic lymph node metastasis (p = 0.044). The median durations of disease-free survival (DFS) and overall survival (OS) were 16.1 and 19.2 months, respectively. The DFS and OS of patients exhibiting high SUVmax of the primary tumour were significantly lower than those of patients exhibiting low SUVmax of the primary tumour (p = 0.0171 and p = 0.0367). The OS of patients exhibiting low ADCmin of the primary tumour was significantly lower than that of patients exhibiting high ADCmin of the primary tumour (p = 0.0376). The DFS and OS of patients exhibiting high SUVmax together with low ADCmin of the primary tumour were significantly lower (p = 0.003 and p = 0.001). Multivariate analyses showed that high SUVmax together with low ADCmin of the primary tumour was an independent prognostic factor for both DFS (p = 0.0030) and OS (p = 0.0036). CONCLUSION: High SUVmax together with low ADCmin of the primary tumour is an important predictive factor for identifying patients with cervical cancer who have a poor prognosis. PMID- 22072287 TI - Mild kidney disease as a risk factor for major bleeding in patients with atrial fibrillation undergoing percutaneous coronary stenting. AB - Bleeding risk is increased in patients with atrial fibrillation (AF) and moderate to severe kidney disease (KD); however, the implication of mild KD on bleeding remains unclear. The aim of this study was to determine whether the presence of mild KD increases risk for major bleeding (MB) in patients with AF undergoing percutaneous coronary intervention with stent implantation (PCI-S). Two hundred eighty-five patients were included. Patients were classified into three kidney function groups: moderate to severe KD (n=91; <60 ml/min/1.73 m2), mild KD (n=139; 60-89 ml/min/1.73 m2) and non-KD (n=55; >=90 ml/min/1.73 m2). Estimated glomerular filtration rate was calculated using the simplified Modification of Diet in Renal Disease equation. Patients were followed for one year, and the occurrence of MB was obtained in all. A total of 28 patients (9.8%) presented MB. MB complications examined as a function of KD groups revealed that there was a graded increase in MB with worsening renal function (non KD=1.8%, mild KD=7.9%, moderate to severe KD=17.6%; p <0.001). Multivariable Cox regression analysis showed that mild KD was associated with nearly a 2.5-fold (2.43 95% confidence interval 1.11-5.34, p=0.039) increase in the risk of MB as compared with non-KD patients. Other independent predictors of MB were moderate-severe KD, anaemia and triple antithrombotic therapy after PCI-S (C-index=0.76). In this population, mild KD confers a significantly increase in the risk for MB complications. Future studies should assess the potential role of incorporating mild KD into the bleeding risk scales to improve the stratification of these patients. PMID- 22072288 TI - Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. AB - Traditionally, muscle physiology experiments require multiple tissue samples to obtain morphometric, electrophysiological, and contractility data. Furthermore, these experiments are commonly completed one at a time on cover slips of single cells, isotropic monolayers, or in isolated muscle strips. In all of these cases, variability of the samples hinders quantitative comparisons among experimental groups. Here, we report the design of a "heart on a chip" that exploits muscular thin film technology--biohybrid constructs of an engineered, anisotropic ventricular myocardium on an elastomeric thin film--to measure contractility, combined with a quantification of action potential propagation, and cytoskeletal architecture in multiple tissues in the same experiment. We report techniques for real-time data collection and analysis during pharmacological intervention. The chip is an efficient means of measuring structure-function relationships in constructs that replicate the hierarchical tissue architectures of laminar cardiac muscle. PMID- 22072289 TI - TGFbeta1-Endo180-dependent collagen deposition is dysregulated at the tumour stromal interface in bone metastasis. AB - Cellular niches in adult tissue can harbour dysregulated microenvironments that become the driving force behind disease progression. The major environmental change when metastatic cells arrive in the bone is the destruction of mineralized type I collagen matrix. Once metastatic niches establish in bone, the invading tumour cells initiate a vicious cycle of osteolytic lesion formation via the dysregulation of paracrine signals and uncoupling of normal bone resorption and production. Here we report that the collagen receptor Endo180 (CD280, MRC2, uPARAP) participates in collagen deposition by primary human osteoblasts during de novo osteoid formation. This newly recognized function of Endo180 was suppressed in osteoblasts following heterotypic direct cell-cell contact in co culture with prostate tumour cells. Reciprocal Endo180 up-regulation in osteolytic prostate tumour cells (PC3 and DU145) followed their direct contact with osteoblasts and promoted de novo collagen internalization, which is a previously characterized function of the constitutively recycling Endo180 receptor. The osteoblastic suppression and tumour cell-associated enhancement of Endo180 expression were equally sustained in these direct co-cultures. These findings are the first to demonstrate that increased tumour cell participation in collagen degradation and decreased collagen formation by osteoblasts in the osteolytic microenvironment are linked to the divergent regulation of a collagen binding receptor. Immunohistochemical analysis of core biopsies from bone metastasis revealed higher levels of Endo180 expression in tumour cell foci than cells in the surrounding stroma. Additional experiments in prostate cell osteoblast co-cultures indicate that divergent regulation of Endo180 is the result of dysregulated TGFbeta1 signalling. The findings of this study provide a rationale for targeting collagen remodelling by Endo180 in bone metastases and other collagen matrix pathologies. PMID- 22072290 TI - Imaging indexes of activity and severity for Crohn's disease: current status and future trends. AB - BACKGROUND: Cross-sectional imaging techniques, including ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) are increasingly used for evaluation of Crohn's disease (CD). AIM: To review the accuracy of cross sectional imaging indexes for measurement of disease activity and severity in patients with CD, and to evaluate its applicability on daily clinical practice and research. METHODS: Relevant publications were identified by literature search, and selected based on predefined quality parameters, including a sample size and reference standard. Nineteen publications were chosen. RESULTS: The US based indexes of activity showed high correlation with reference standard indexes. There is a good or very good agreement between the MR-based indexes and the reference standard when the comparison is limited to small segments of intestine. Significant discrepancies have been found between indexes that evaluate the colon. Only one CT-based index was included. The main strengths and weaknesses of the indexes, according to its design, are discussed. CONCLUSION: Standardization of image acquisition protocols and patient preparation should be procured, especially for MRI. In daily practice, a simple, semi-quantitative index providing relevant information on disease activity and severity is preferable. For research purposes, a precise and reproducible index should be mandatory. PMID- 22072293 TI - The combination of four different clinical decision rules and an age-adjusted D dimer cut-off increases the number of patients in whom acute pulmonary embolism can safely be excluded. AB - Four clinical decision rules (CDRs) (Wells score, Revised Geneva Score (RGS), simplified Wells score and simplified RGS) safely exclude pulmonary embolism (PE), when combined with a normal D-dimer test. Recently, an age-adjusted cut-off of the D-dimer (patient's age x 10 MUg/l) safely increased the number of patients above 50 years in whom PE could safely be excluded. We validated the age-adjusted D-dimer test and assessed its performance in combination with the four CDRs in patients with suspected PE. A total of 414 consecutive patients with suspected PE who were older than 50 years were included. The proportion of patients in whom PE could be excluded with an 'unlikely' clinical probability combined with a normal age-adjusted D-dimer test was calculated and compared with the proportion using the conventional D-dimer cut-off. We assessed venous thromboembolism (VTE) failure rates during three months follow-up. In patients above 50 years, a normal age-adjusted D-dimer level in combination with an 'unlikely' CDR substantially increased the number of patients in whom PE could be safely excluded: from 13-14% to 19-22% in all CDRs similarly. In patients over 70 years, the number of exclusions was nearly four-fold higher, and the original Wells score excluded most patients, with an increase from 6% to 21% combined with the conventional and age-adjusted D-dimer cut-off, respectively. The number of VTE failures was also comparable in all CDRs. In conclusion, irrespective of which CDR is used, the age adjusted D-dimer substantially increases the number of patients above 50 years in whom PE can be safely excluded. PMID- 22072294 TI - The role of the syllable in the segmentation of Cairene spoken Arabic. AB - The syllable as a perceptual unit has been investigated cross linguistically. In Cairene Arabic syllables fall into three categories, light CV, heavy CVC/CVV and superheavy CVCC/CVVC. However, heavy syllables in Cariene Arabic have varied weight depending on their position in a word, whether internal or final. The present paper investigates the role of the syllable in the segmentation of Cariene Arabic. It reports a psycholinguistic study; syllable monitoring that was conducted on 32 Egyptian Arabic native speakers to examine the perceptual role of the syllable in spoken connected language. Theoretical phonological studies have identified Cairene Arabic as a stress-timed language; however, psycholinguistic studies providing evidence for this theoretical finding are scarce. The present study which is a cross modal (visual and auditory) counterbalanced design, gives evidence for the role of the (CVC) syllable in the segmentation of Cairene spoken language. PMID- 22072291 TI - The role of MOF in the ionizing radiation response is conserved in Drosophila melanogaster. AB - In Drosophila, males absent on the first (MOF) acetylates histone H4 at lysine 16 (H4K16ac). This acetylation mark is highly enriched on the male X chromosome and is required for dosage compensation in Drosophila but not utilized for such in mammals. Recently, we and others reported that mammalian MOF, through H4K16ac, has a critical role at multiple stages in the DNA damage response (DDR) and double-strand break repair pathways. The goal of this study was to test whether mof is similarly required for the response to ionizing radiation (IR) in Drosophila. We report that Drosophila mof mutations in males and females, as well as mof knockdown in SL-2 cells, reduce post-irradiation survival. MOF depletion in SL-2 cells also results in an elevated frequency of metaphases with chromosomal aberrations, suggesting that MOF is involved in DDR. Mutation in Drosophila mof also results in a defective mitotic checkpoint, enhanced apoptosis, and a defective p53 response post-irradiation. In addition, IR exposure enhanced H4K16ac levels in Drosophila as it also does in mammals. These results are the first to demonstrate a requirement for MOF in the whole animal IR response and suggest that the role of MOF in the response to IR is conserved between Drosophila and mammals. PMID- 22072295 TI - Current world literature. PMID- 22072297 TI - SCOUT: A Fast Monte-Carlo Modeling Tool of Scintillation Camera Output. AB - We have developed a Monte-Carlo photon-tracking and readout simulator called SCOUT to study the stochastic behavior of signals output from a simplified rectangular scintillation-camera design. SCOUT models the salient processes affecting signal generation, transport, and readout. Presently, we compare output signal statistics from SCOUT to experimental results for both a discrete and a monolithic camera. We also benchmark the speed of this simulation tool and compare it to existing simulation tools. We find this modeling tool to be relatively fast and predictive of experimental results. Depending on the modeled camera geometry, we found SCOUT to be 4 to 140 times faster than other modeling tools. PMID- 22072298 TI - Lateral cavity acoustic transducer as an on-chip cell/particle microfluidic switch. AB - A novel on-chip microfluidic switch is demonstrated that utilizes the acoustic microstreaming generated by an oscillating air-liquid interface to switch cells/particles into bifurcating microchannels. The air-liquid interface of the Lateral Cavity Acoustic Transducers (LCATs) can be actuated by an external acoustic energy source causing the interface to oscillate. The oscillating interface results in the generation of vortex-like microstreaming flow within a localized region of the surrounding liquid. This streaming was utilized here to deflect cells/particles into a collection outlet. It was demonstrated that the switching zone could be controlled by varying the actuation time of the LCAT. An LCAT based microfluidic switch is capable of achieving theoretical switching rates of 800 cells/particles per second. It was also demonstrated that K562 cells could be switched into a collection channel with cell viability comparable to that of controls as determined by Trypan blue exclusion assay. PMID- 22072299 TI - The open-chain triphosphanes RMe2SiCH2P(PR'2)2 (R = Me, Ph; R' = SiMe3, Cy, Ph). AB - The triphosphanes RMe(2)SiCH(2)P(PR'(2))(2) (R = Me, Ph; R' = SiMe(3), Cy) are synthesised in good yield via metathesis of organodichlorophosphanes and LiPR'(2), while for R' = Ph a propensity to form (Ph(2)P)(2) precludes isolation of the in situ characterised triphosphanes. Where R = Me and R' = SiMe(3) the triphosphane has also been characterised by single crystal X-ray diffraction and exhibits a single geometric conformer in the solid state, though solution-phase NMR spectra are indicative of facile conformational exchange across a wide temperature range. All of the described triphosphanes exhibit comparable behaviour, with their respective (31)P{(1)H} NMR spectra manifesting anomalous 'second-order' characteristics, which are considered using full spin-Hamiltonian simulation. Preliminary studies of coordination chemistry and ancillary reactivity of the triphosphanes are described. PMID- 22072300 TI - Use of brain natriuretic peptide to detect previously unknown left ventricular dysfunction in patients with acute exacerbation of chronic obstructive pulmonary disease. AB - BACKGROUND: Up to 30% of patients with chronic obstructive pulmonary disease (COPD) simultaneously suffer from often-unrecognised chronic heart failure (HF). Their timely identification is challenging as both conditions share similar clinical presentations. OBJECTIVE: To assess the performance of BNP in detecting left ventricular systolic dysfunction in patients with no history of HF admitted for acute exacerbation of COPD in a regional second-care hospital. METHODS: Retrospective medical records analysis of all patients hospitalised between January 2003 and May 2009 with the final diagnosis of acute exacerbation of COPD, and who had undergone BNP dosage at admission followed by an echocardiography. RESULTS: Among the 57 patients included, 13 had left ventricular systolic dysfunction. There was a statistically significant difference of mean BNP values between patients with or without systolic dysfunction (mean 689 pg/ml vs. 340 pg/ml, p = 0.007). For the detection of systolic dysfunction, a BNP level inferior to 100 pg/ml yielded a sensitivity of 92% and a negative predictive value of 91%, whereas BNP higher than 500 yielded a sensitivity of 80% and a positive predictive value of 47%. In a multivariate logistic regression analysis, a BNP value >=500 (odds ratio 8.5, 95% confidence interval 1.9 to 38.2, p = 0.005) and history of coronary heart disease (odds ratio 5.9, 95% confidence interval 1.01 to 34.7, p = 0.048) remained as independent and mutually adjusted predictors of left ventricular systolic dysfunction. CONCLUSIONS: Our study confirms that BNP can help physicians in identifying heart failure in patients suffering from an acute exacerbation of COPD. PMID- 22072301 TI - [Update hip surgery : New trends and current operation techniques]. PMID- 22072302 TI - Genetic deletion of 5-lipoxygenase increases tumor-infiltrating macrophages in Apc(Delta468) mice. AB - INTRODUCTION: The role of 5-lipoxygenase (5-LO) in colon cancer is unknown. Tumor infiltrating macrophages, neutrophils, and mast cells have been shown to play important roles in colon tumorigenesis and are dependent on 5-LO for function. METHODS AND MATERIALS: Utilizing the APC(Delta468) polyposis model, we performed 5-LO gene knockouts and evaluated the subsequent changes in macrophage, neutrophil, and mast cell density at the tumor site. The proliferative and degranulation capacities of 5-LO-deficient mast cells were also measured, quantifying thymidine incorporation and beta-hexosaminidase release, respectively. RESULTS: APC(Delta468)/5LO(-/-) mice displayed increased tumor infiltrating macrophages and decreased neutrophils at the polyp site. In vitro, mast cells deficient for 5-LO proliferated at a diminished rate while mast cell degranulation was unchanged. DISCUSSION: We provide evidence suggesting that 5-LO deficiency has differential effects on the infiltration of macrophages and neutrophils in adenomatous polyps, increasing and decreasing infiltration of these cells, respectively. Our observations are consistent with a protective role for tumor-infiltrating macrophages in the initiation of polyp formation. The mechanisms through which 5-LO deficiency negatively affects these cells are under investigation. CONCLUSIONS: These results provide evidence that 5-LO plays an important role in tumorigenesis and further indicate that 5-LO-selective inhibitors can be investigated as potential therapeutic agents for colorectal polyposis and cancer. PMID- 22072303 TI - High expression of CCL20 is associated with poor prognosis in patients with hepatocellular carcinoma after curative resection. AB - INTRODUCTION: Chemokine ligand 20 (CCL20) plays an important role in the carcinogenesis, invasion, and progression of malignancies. This study aimed to investigate the prognostic significance of CCL20 in patients with hepatocellular carcinoma (HCC) after curative resection. METHODS: Expression of CCL20 was evaluated by immunohistochemistry in tumor tissue from 125 patients who underwent curative resection of HCC. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for tumor recurrence and survival of HCC patients. RESULTS: CCL20 expression was verified in all tumor specimens. CCL20 expression was associated with tumor size (P = 0.002), tumor number (P = 0.031), vascular invasion (P = 0.003), tumor differentiation (P = 0.024), and tumor recurrence (P < 0.001). Patients with high CCL20 expression had poorer recurrence-free survival and overall survival (both P < 0.001) than those with low CCL20 expression. Multivariate analysis showed CCL20 expression was an independent predictor of tumor recurrence (Hazard ratio 3.934, P = 0.002), recurrence-free survival (Hazard ratio 2.573, P = 0.001), and overall survival (Hazard ratio 2.930, P = 0.001). CONCLUSION: CCL20 expression was associated with tumor recurrence and survival of HCC patients. It may be used to predict prognosis of patients with HCC and may be a new target of postoperative adjuvant therapy. PMID- 22072305 TI - Development of an ELISA to detect the secreted prostate cancer biomarker AGR2 in voided urine. AB - BACKGROUND: Comparative transcriptomics between sorted cells identified AGR2 as one of the highest up-regulated genes in cancer. Overexpression in primary tumors was verified by tissue microarray analysis. AGR2 encodes a 19-kDa secreted protein that might be found in urine. METHODS: Monoclonal antibodies were generated against AGR2. One antibody pair, P1G4 (IgG1) to capture and P3A5 (IgG2a) to detect, showed good performance characteristics in a sandwich ELISA. This assay could detect AGR2 at sub ng/ml quantities. RESULTS: AGR2 was detected in tissue digestion media of tumor specimens and culture media of AGR2-secreting prostate cancer cell lines. Additional testings involved frozen section immunohistochemistry, immunoprecipitation, and Western blot analysis. Voided urine samples were collected from pre-operative cancer patients, and urinary protein was desalted and concentrated by filtration. The amount of AGR2 detected was scored as pg/100 ug total protein, and then converted to pg/ml urine. The developed ELISA detected AGR2 protein, ranging from 3.6 to 181 pg/ml, in an initial cohort of samples. AGR2 was not detected in the urine of non-cancer and a bladder cancer patient. CONCLUSIONS: For prostate cancer, an AGR2 urine test could be used for diagnosis. The data, although derived from a small number of samples assayed, showed that developing such a test for clinical application is viable because AGR2 is specific to cancer cells, and apparently secreted into urine. PMID- 22072304 TI - Mobile laminar air flow screen for additional operating room ventilation: reduction of intraoperative bacterial contamination during total knee arthroplasty. AB - BACKGROUND: Surgical site infections are important complications in orthopedic surgery. A mobile laminar air flow (LAF) screen could represent a useful addition to an operating room (OR) with conventional turbulent air ventilation (12.5 air changes/h), as it could decrease the bacterial count near the operating field. The purpose of this study was to evaluate LAF efficacy at reducing bacterial contamination in the surgical area during 34 total knee arthroplasties (TKAs). MATERIALS AND METHODS: The additional unit was used in 17 operations; the LAF was positioned beside the operating table between two of the surgeons, with the air flow directed towards the surgical area (wound). The whole team wore conventional OR clothing and the correct hygiene procedures and rituals were used. Bacterial air contamination (CFU/m(3)) was evaluated in the wound area in 17 operations with the LAF unit and 17 without the LAF unit. RESULTS: The LAF unit reduced the mean bacterial count in the wound area from 23.5 CFU/m(3) without the LAF to 3.5 CFU/m(3) with the LAF (P < 0.0001), which is below the suggested limit for an OR with ultraclean laminar ventilation. There were no significant differences in the mean bacterial count in the instrument table area: 28.6 CFU/m(3) were recorded with the LAF (N = 6) unit and 30.8 CFU/m(3) (N = 6) without the LAF unit (P = 0.631). During six operations with LAF and six without LAF, particle counts were performed and the number of 0.5 MUm particles was analyzed. The particle counts decreased significantly when the LAF unit was used (P = 0.003). CONCLUSION: When a mobile LAF unit was added to the standard OR ventilation, bacterial contamination of the wound area significantly decreased to below the accepted level for an ultraclean OR, preventing SSI infections. PMID- 22072306 TI - Intravascular papillary endothelial hyperplasia of the internal auditory canal. AB - Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's tumor, is a rare vascular lesion characterized by intravascular proliferation of endothelial-lined papillae and a propensity for manifestation in the head and neck. Signs and symptoms associated with IPEH generally occur due to compressive effects of the lesion on adjacent structures. A rare instance of IPEH occurring in the internal auditory canal is presented herein. Clinical presentation, radiographic and pathologic findings, and management strategies are discussed. PMID- 22072307 TI - A multicenter, randomized, phase 2 clinical trial to evaluate the efficacy and safety of combination docetaxel and carboplatin and sequential therapy with docetaxel then carboplatin in patients with recurrent platinum-sensitive ovarian cancer. AB - BACKGROUND: The aim of this randomized clinical trial was to evaluate the efficacy and safety of combination (cDC) and sequential (sDC) weekly docetaxel and carboplatin in women with recurrent platinum-sensitive epithelial ovarian cancer (EOC). METHODS: Participants were randomized to either weekly docetaxel 30 mg/m(2) on days 1 and 8 and carboplatin area under the curve (AUC) = 6 on day 1, every 3 weeks or docetaxel 30 mg/m(2) on days 1 and 8, every 3 weeks for 6 cycles followed by carboplatin AUC = 6 on day 1, every 3 weeks for 6 cycles or until disease progression. The primary endpoint was measurable progression-free survival (PFS). RESULTS: Between January 2004 and March 2007, 150 participants were enrolled. The response rate was 55.4% and 43.2% for those treated with cDC and sDC, respectively. The median PFS was 13.7 months (95% confidence interval [CI], 9.9-16.8) for cDC and 8.4 months (95% CI, 7.1-11.0) for sDC. On the basis of an exploratory analysis, patients treated with sDC were at a 62% increased risk of disease progression compared to those treated with cDC (hazard ratio = 1.62; 95% CI, 1.08-2.45; P = .02). The median overall survival time was similar in both groups (33.2 and 30.1 months, P = .2). The incidence of grade 2 or 3 neurotoxicity and grade 3 or 4 neutropenia was higher with cDC than with sDC (11.7% vs 8.5%; 36.8% vs 11.3%). The sDC group demonstrated significant improvements in the Functional Assessment for Cancer Therapy-Ovarian, Quality of Life Trial Outcome Index scores compared with the combination cohort (P = .013). CONCLUSIONS: Both cDC and sDC regimens have activity in recurrent platinum sensitive EOC with acceptable toxicity profiles. The cDC regimen may provide a PFS advantage over sDC. PMID- 22072308 TI - Leishmanicidal and antitumoral activities of endophytic fungi associated with the Antarctic angiosperms Deschampsia antarctica Desv. and Colobanthus quitensis (Kunth) Bartl. AB - A total of 564 isolates of endophytic fungi were recovered from the plants Deschampsia antarctica and Colobanthus quitensis collected from Antarctica. The isolates were screened against parasites Leishmania amazonensis and Trypanosoma cruzi and against the human tumour cell lines. Of the 313 fungal isolates obtained from D. antarctica and 251 from C. quitensis, 25 displayed biological activity. Nineteen extracts displayed leishmanicidal activity, and six inhibited the growth of at least one tumour cell line. These fungi belong to 19 taxa of the genera Alternaria, Antarctomyces, Cadophora, Davidiella, Helgardia, Herpotrichia, Microdochium, Oculimacula, Phaeosphaeria and one unidentified fungus. Extracts of 12 fungal isolates inhibited the proliferation of L. amazonesis at a low IC(50) of between 0.2 and 12.5 MUg ml(-1). The fungus Phaeosphaeria herpotrichoides displayed only leishmanicidal activity with an IC(50) of 0.2 MUg ml(-1), which is equivalent to the inhibitory value of amphotericin B. The extract of Microdochium phragmitis displayed specific cytotoxic activity against the UACC-62 cell line with an IC(50) value of 12.5 MUg ml(-1). Our results indicate that the unique angiosperms living in Antarctica shelter an interesting bioactive fungal community that is able to produce antiprotozoal and antitumoral molecules. These molecules may be used to develop new leishmanicidal and anticancer drugs. PMID- 22072310 TI - Mutation rate estimates for 13 STR loci in a large population from Rio Grande do Sul, Southern Brazil. AB - Short tandem repeat (STR) polymorphisms have been extensively used in forensic genetics analysis. Knowledge about the locus-specific mutation rates of STRs improves forensic probability calculations and interpretations of diversity data. To incorporate single-locus diversity information into autosomal STR mutation rate estimations, 13 STR loci were studied during 2007-2009 in 10,959 paternity investigation cases from Rio Grande do Sul, the southernmost state of Brazil, covering an overall number of 284,934 allelic transfers. A total of 355 mutations were identified; 348 repeats were gains or losses of one step, three were gains or losses of two steps, and four were gains or losses of not stepwise mutation. The mutation rates ranged from 4.6 * 10(-5) to 2.3 * 10(-3), and the overall mutation rate estimate was 1.2 * 10(-3). The average of the paternal mutation rate (1.8 * 10(-3)) was five times higher than the maternal rate (0.36 * 10(-3)). The observed mutational features for STRs have important consequences for forensic applications, including the definition of criteria for exclusion in paternity testing and the interpretation of DNA profiles in identification analysis. PMID- 22072309 TI - Human age estimation combining third molar and skeletal development. AB - The wide prediction intervals obtained with age estimation methods based on third molar development could be reduced by combining these dental observations with age-related skeletal information. Therefore, on cephalometric radiographs, the most accurate age-estimating skeletal variable and related registration method were searched and added to a regression model, with age as response and third molar stages as explanatory variable. In a pilot set up on a dataset of 496 (283 M; 213 F) cephalometric radiographs, the techniques of Baccetti et al. (2005) (BA), Seedat et al. (2005) (SE), Caldas et al. (2007) and Rai et al. (2008) (RA) were verified. In the main study, data from 460 (208 F, 224 M) individuals in an age range between 3 and 26 years, for which at the same day an orthopantogram and a cephalogram were taken, were collected. On the orthopantomograms, the left third molar development was registered using the scoring system described by Gleiser and Hunt (1955) and modified by Kohler (1994) (GH). On the cephalograms, cervical vertebrae development was registered according to the BA and SE techniques. A regression model, with age as response and the GH scores as explanatory variable, was fitted to the data. Next, information of BA, SE and BA + SE was, respectively, added to this model. From all obtained models, the determination coefficients and the root mean squared errors were calculated. Inclusion of information from cephalograms based on the BA, as well as the SE, technique improved the amount of explained variance in age acquired from panoramic radiographs using the GH technique with 48%. Inclusion of cephalometric BA + SE information marginally improved the previous result (+1%). The RMSE decreased with 1.93, 1.85 and 2.03 years by adding, respectively, BA, SE and BA + SE information to the GH model. The SE technique allows clinically the fastest and easiest registration of the degree of development of the cervical vertebrae. Therefore, the choice of technique to classify cervical vertebrae development in addition to third molar development is preferably the SE technique. PMID- 22072311 TI - Pulmonary embolisation of bone fragments from penetrating cranial gunshot wounds. AB - Bone embolism is a very rare event that usually occurs in trauma-induced septic bone lesions, after bone surgery or after bone marrow transplantation, and normally remains silent. To our knowledge, there are no previous reports of bone embolism after a gunshot to the head. We describe a case of pulmonary embolism associated with bone fragments after a gunshot to the head in which bone fragments surrounded by leukocytes, interstitial and intra-alveolar oedema and haemorrhage around the embolised vessels, leukostasis and fat and bone marrow embolism suggest that the survival time from the gunshot was sufficiently long to allow changes in lung microcirculation and lung tissue. PMID- 22072312 TI - GFAP-independent inflammatory competence and trophic functions of astrocytes generated from murine embryonic stem cells. AB - The directed generation of pure astrocyte cultures from pluripotent stem cells has proven difficult. Generation of defined pluripotent-stem-cell derived astrocytes would allow new approaches to the investigation of plasticity and heterogeneity of astrocytes. We here describe a two-step differentiation scheme resulting in the generation of murine embryonic stem cell (mESC) derived astrocytes (MEDA), as characterized by the upregulation of 19 astrocyte associated mRNAs, and positive staining of most cells for GFAP (glial fibrillary acidic protein), aquaporin-4 or glutamine synthetase. The MEDA cultures could be cryopreserved, and they neither contained neuronal, nor microglial cells. They also did not react to the microglial stimulus lipopolysaccharide, while inflammatory activation by a complete cytokine mix (CCM) or its individual components (TNF-alpha, IL1-beta, IFN-gamma) was readily observed. MEDA, stimulated by CCM, became susceptible to CD95 ligand-induced apoptosis and produced NO and IL-6. This was preceded by NF-kB activation, and up-regulation of relevant mRNAs. Also GFAP-negative astrocytes were fully inflammation-competent. Neurotrophic support by MEDA was found to be independent of GFAP expression. In summary, we described here the generation and functional characterization of microglia-free murine astrocytes, displaying phenotypic heterogeneity as is commonly observed in brain astrocytes. PMID- 22072313 TI - Enhancement of DNA hybridization under acoustic streaming with three piezoelectric-transducer system. AB - Recently, we have demonstrated that DNA hybridization using acoustic streaming induced by two piezoelectric transducers provides higher DNA hybridization efficiency than the conventional method. In this work, we refine acoustic streaming system for DNA hybridization by inserting an additional piezoelectric transducer and redesigning the locations of the transducers. The Comsol(r) Multiphysics was used to design and simulate the velocity field generated by the piezoelectric agitation. The simulated velocity vector followed a spiral vortex flow field with an average direction outward from the center of the transducers. These vortices caused the lower signal intensity in the middle of the microarray for the two-piezoelectric disk design. On the contrary, the problem almost disappeared in the three-piezoelectric-disk system. The optimum condition for controlling the piezoelectric was obtained from the dye experiments with different activation settings for the transducers. The best setting was to activate the side disks and middle disk alternatively with 1 second activating time and 3 second non-activating time for both sets of transducers. DNA hybridization using microarrays for the malaria parasite Plasmodium falciparum from the optimized process yielded a three-fold enhancement of the signal compared to the conventional method. Moreover, a greater number of spots passed quality control in the optimized device, which could greatly improve biological interpretation of DNA hybridization data. PMID- 22072314 TI - Non-crossbridge calcium-dependent stiffness in slow and fast skeletal fibres from mouse muscle. AB - We showed previously that force development in frog and FDB mouse skeletal muscle fibres is preceded by an increase of fibre stiffness occurring well before crossbridge attachment and force generation. This stiffness increase, referred to as static stiffness, is due to a Ca(2+)-dependent stiffening of a non-crossbridge sarcomere structure which we suggested could be attributed to the titin filaments. To investigate further the role of titin in static stiffness, we measured static stiffness properties at 24 and 35 degrees C in soleus and EDL mouse muscle fibres which are known to express different titin isoforms. We found that static stiffness was present in both soleus and EDL fibres, however, its value was about five times greater in EDL than in soleus fibres. The rate of development of static stiffness on stimulation increased with temperature and was slightly faster in EDL than in soleus in agreement with previously published data on the time course of the intracellular Ca(2+) transients in these muscles. The present results show that the presence of a non-crossbridge Ca(2+)-dependent stiffening of the muscle fibre is a physiological general characteristic of skeletal muscle. Static stiffness depends on fibre type, being greater and developing faster in fast than in slow fibres. Our observations are consistent with the idea that titin stiffening on contraction improves the sarcomere structure stability. Such an action in fact seems to be more important in EDL fast fibre than in soleus slow fibres. PMID- 22072315 TI - Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006. AB - BACKGROUND: Recent trends indicate a change in the epidemiology of inflammatory bowel diseases (IBD), with previously low incidence areas now reporting a progressive rise in the incidence. Our aim was to analyze the incidence and disease phenotype at diagnosis in IBD in the population-based Veszprem Province database, which included incident patients diagnosed between January 1, 2002 and December 31, 2006. METHODS: Data of 393 incident patients were analyzed (ulcerative colitis [UC]: 220, age-at-diagnosis: 40.5 years; Crohn's disease [CD]: 163, age-at-diagnosis: 32.5 years; and indeterminate colitis [IC]: 10). Both hospital and outpatient records were collected and comprehensively reviewed. RESULTS: Adjusted mean incidence rates were 8.9/10(5) person-years for CD and 11.9/10(5) person-years in UC. Peak onset age in both CD and UC patients was 21 30 years old. Location at diagnosis in UC was proctitis in 26.8%, left-sided colitis in 50.9%, and pancolitis in 22.3%. The probability of proximal extension and colectomy after 5 years was 12.7% and 2.8%. The disease location in CD was ileal in 20.2%, colonic in 35.6%, ileocolonic in 44.2%, and upper gastrointestinal in four patients. Behavior at diagnosis was stenosing/penetrating in 35.6% and perianal in 11.1%. Patients with colonic disease were older at diagnosis compared to patients with ileal or ileocolonic disease. In a Kaplan-Meier analysis, probability of surgical resection was 9.8%, 18.5%, and 21.3% after 1, 3, and 5 years of disease duration, respectively. CONCLUSIONS: The incidence of IBD in Veszprem Province in the last decade was high, equal to that in high-incidence areas in Western European countries. Early disease course is milder compared to data reported in the literature. PMID- 22072317 TI - Genome-wide differential genetic profiling characterizes colorectal cancers with genetic instability and specific routes to HLA class I loss and immune escape. AB - AIM: We compared the expression of genes related to inflammatory and cytotoxic functions between MSI and MSS (HLA-class I-negative and HLA-class I-positive) colorectal cancers (CRCs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two CRCs were divided into three study groups as a function of HLA class I expression and MSI phenotype: 8 MSI tumours, 6 MSS/HLA- tumours and 6 MSS/HLA+ tumours (controls). FINDINGS: A first comparison between eight MSI and six MSS/HLA-positive (control) cancers, based on microarray analysis on an Affymetrix((r)) HG-U133-Plus-PM plate, identified 1974 differentially expressed genes (P < 0.05). We grouped genes in Gene Ontology functional categories: apoptotic programme (72 genes, P = 5.5.10(-3)), leucocyte activation (43 genes, P = 1.8.10(-5)), T-cell activation (24 genes, P = 6.3.10( 4)), inflammatory response (40 genes, 2.3.10(-2)) and cytokine production (10 genes, P = 1.9.10(-2)). Real-time PCR and immunohistochemical evaluation were used to validate the data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+T lymphocytes in the MSI group (P < 0.001). Finally, HLA-class I-negative tumours were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-class I-negative CRCs (n = 6) in comparison to controls. CONCLUSIONS: In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumour, MSI/HLA-class I-negative and MSS/HLA-class I negative, showed marked differences in the composition and intensity of infiltrating leucocytes, suggesting that their immune escape strategies involve distinct pathways. PMID- 22072316 TI - DHPLC/SURVEYOR nuclease: a sensitive, rapid and affordable method to analyze BRCA1 and BRCA2 mutations in breast cancer families. AB - Hereditary breast cancer accounts for about 10% of all breast cancers and BRCA1 and BRCA2 genes have been identified as validated susceptibility genes for this pathology. Testing for BRCA gene mutations is usually based on a pre-screening approach, such as the partial denaturation DHPLC method, and capillary direct sequencing. However, this approach is time consuming due to the large size of BRCA1 and BRCA2 genes. Recently, a new low cost and time saving DHPLC protocol has been developed to analyze gene mutations by using SURVEYOR((r)) Nuclease digestion and DHPLC analysis. A subset of 90 patients, enrolled in the Genetic Counseling Program of the National Cancer Centre of Bari (Italy), was performed to validate this approach. Previous retrospective analysis showed that 9/90 patients (10%) were mutated in BRCA1 and BRCA2 genes and these data were confirmed by the present approach. DNA samples underwent touchdown PCR and, subsequently, SURVEYOR((r)) nuclease digestion. BRCA1 and BRCA2 amplicons were divided into groups depending on amplicon size to allow multiamplicon digestion. The product of this reaction were analyzed on Transgenomic WAVE Nucleic Acid High Sensitivity Fragment Analysis System. The operator who performed the DHPLC surveyor approach did not know the sequencing results at that time. The SURVEYOR((r)) Nuclease DHPLC approach was able to detect all alterations with a sensitivity of 95%. Furthermore, in order to save time and reagents, a multiamplicon setting preparation was validated. PMID- 22072318 TI - Co-culturing mesenchymal stem cells from bone marrow and periosteum enhances osteogenesis and neovascularization of tissue-engineered bone. AB - Mesenchymal stem cells (MSCs) isolated from bone marrow and periosteum are often used as cellular sources for bone tissue engineering. This study showed that co cultured human bone marrow stem cells (hBMSCs) and periosteal-derived stem cells (hPCs) resulted in a synergistic effect on osteogenic differentiation both in vitro and in vivo. Compared to hBMSCs and hPCs, co-culturing MSCs showed abundant mineralization, robust calcium deposition, steadily increasing ALP activity, and upgraded mRNA expression of osteogenic specific genes (COL1A1, BMP-2, osteopontin, osteocalcin) in vitro. Eight weeks after implantation of cellular beta-TCP scaffolds in immunodeficient mice, similar synergistic effects were confirmed during in vivo evaluation of total new bone formation, mature bone formation, and neovascularization. Based on these findings, the use of co cultured hBMSCs and hPCs can be recommended as a promising new approach for bone tissue engineering applications. PMID- 22072320 TI - Does participation in clinical trials influence the costs of future management of patients? AB - BACKGROUND: An earlier study showed that from a societal perspective it was less expensive to encourage patients to self-regulate their medication for GERD (gastro-esophageal reflux disease) by treating patients on-demand. OBJECTIVE: The objective was to investigate whether physician involvement in a clinical trial financed by the pharmaceutical industry subsequently results in higher health care costs. STUDY DESIGN: An open, observational, multicenter study compared direct medical costs and total costs for three groups of patients with different exposure to the clinical trial; (1) Dual exposed, where both the patients and the GP participated in the former clinical trial, (2) GP exposed, where only the GP participated in the former clinical trial and (3) nonexposed, where neither the patients nor the GP participated in the former clinical trial. RESULTS: We did not find any statistically significant differences in neither direct medical nor total costs. However, we did observe a numerical difference in direct medical costs of 24% higher in the dual exposed group compared to the nonexposed group mainly due to a higher consumption of prescribed medication. The higher direct medical cost in the dual exposed group was however counterbalanced by lower observed direct nonmedical and indirect costs. CONCLUSION: Although we did not find any statistical significant differences in health care costs, we did observe a higher consumption of prescribed medication and lower costs of work hours lost if both patient and GPs participated in a former clinical trial. The results may be limited due to a lower number of patients included than expected. PMID- 22072321 TI - Trends in social class inequalities in the use of health care services within the Spanish National Health System, 1993-2006. AB - OBJECTIVE: The aim of this study was to analyse the trends and socio-economic inequalities in the use of health care services in Spain between 1993 and 2006. METHODS: A study of trends was performed using data from six Spanish National Health Surveys (1993, 1995, 1997, 2001, 2003 and 2006). Sample sizes were 21,061; 6,396; 6,396; 21,066; 21,650 and 29,478, respectively. The following dependent variables were analysed: having visited a general practitioner (GP) or specialist in the previous 2 weeks, having visited a dentist within the previous 3 months and having visited a gynaecologist, having used the emergency services or having been hospitalised in the previous year. The main independent variable was social class, classified as manual or non-manual occupation. For each service, age standardised proportions of use were calculated by survey year, sex and social class, and indices of relative (RII) and absolute (SII) inequality were computed. Trend tests were applied. RESULTS: An increase in the proportion of use was observed for all services, particularly emergency services. Individuals from manual classes were more likely to visit the GP and emergency services than those from non-manual classes. Conversely, those from non-manual classes were more likely to use specialised services. This trend was most notable for dentist visits. Social inequalities did not change significantly during the study period. CONCLUSIONS: Despite the increase in the use of health care services, the relationship between social class and the use of these services has remained stable throughout the study period. Achieving equity in the use of specialised care services is still a challenge for universal health care systems. PMID- 22072322 TI - High tibial osteotomy in medial compartment osteoarthritis and varus deformity using the Taylor spatial frame: early results. AB - We report the early results of high tibial osteotomy (HTO) in medial compartment osteoarthritis (OA) and varus deformity using the Taylor spatial frame (TSF). Between October 2005 and April 2007, 9 patients with medial compartment OA and varus deformity underwent TSF application and medial opening wedge HTO. Pre- and post-operative Oxford knee scores, SF-12 and visual analogue pain scores were recorded along with radiographic outcomes. Median follow-up was 19 months (range 15-35). Mean age at operation was 49 years (range 37-59). The median time spent in the frame was 18 weeks (range 12-37). The mean preoperative Oxford knee score was 28.7. This improved to a mean of 35.4 post-operatively (P = 0.0142). 6 (67%) patients had a documented pin-site infection. With TKR as an end point, the survival rate of HTOs was 88.9% at a median of 19 months follow-up. This study demonstrates that in selected patients the TSF provides a viable treatment option for performing HTO in medial compartment OA with varus deformity. PMID- 22072323 TI - Transarticular drilling for stable juvenile osteochondritis dissecans of the medial femoral condyle. AB - PURPOSE: Drilling is the most common operative treatment for stable juvenile osteochondritis dissecans (OCD) of the knee. However, prognostic factors remain unclear because of lack of precise radiographic and histopathologic investigations. The purpose of this study was to evaluate the clinical results and prognostic factor of the arthroscopic drilling for juvenile OCD lesions at the medial femoral condyle (MFC), using computed tomography (CT) images. METHODS: Eighteen skeletally immature patients (boys, n = 16; girls, n = 2, mean age, 12 years) underwent arthroscopic antegrade transarticular drilling for a total of 19 OCD lesions of MFC. Functional outcomes were evaluated with the Lysholm score at follow-up (mean, 30 months). Preoperative osteochondral condition and postoperative healing were evaluated by CT images. RESULTS: All 18 patients returned to their previous level of sports activity and showed excellent functional outcomes (mean Lysholm score, 77.2 +/- 9.4 preoperative vs. 99.5 +/- 1.6 postoperative). There were 10 osteochondral lesions and 9 subchondral bone defect lesions under preoperative CT examination. Postoperatively, 15 of 19 lesions healed completely at a mean of 6 months; however, the remaining four lesions (all osteochondral types) did not achieve complete radiographic healing after 2 years. CONCLUSION: Transarticular drilling for stable juvenile OCD produced excellent functional outcomes. However, the osteochondral type may influence radiographic outcome. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 22072324 TI - Long-term survival analysis of posterior cruciate-retaining total knee arthroplasty. AB - PURPOSE: Clinical factors related to cruciate-retaining knee arthroplasty failure in a long-term follow-up are yet unclear. The study was designed to evaluate the long-term survival rate of cruciate-retaining arthroplasty and clinical factors that may contribute to its failure. METHODS: A total of 162 patients (188 knees) who received cruciate-retaining press-fit condylar arthroplasty from June 1993 to May 1994 were followed up. All patients were assessed clinically and radiographically. Revision for any reason was regarded as failure of arthroplasty. RESULTS: A total of 120 patients (138 knees) were successfully followed up. Survivorship over 17 years was 92.5%. Fourteen knees were revised. Tibial varus angle of the operated knee in the unrevised patient group was greater than in revised group. There was statistical difference between these two groups (P < 0.05). CONCLUSION: Long-term survivorship of cruciate-retaining arthroplasty was fair. Varus and valgus deformity of the unoperated contralateral knee and tibial varus deformity of the operated knee could be important factors related to arthroplasty failure. CLINICAL RELEVANCE: This long-term follow-up result of Press-Fit Condylar cruciate-retaining arthroplasty was good considering it was an old design. The alignment of the operated knee and deformity of the unoperated contralateral knee are important clinical factors that should be paid attention to avoid unexpected arthroplasty failure. LEVEL OF EVIDENCE: IV. PMID- 22072325 TI - A comparative study of two methods for treating type III tibial eminence avulsion fracture in adults. AB - PURPOSE: Suture fixation is mostly used in arthroscopic treatment of tibial eminence avulsion fractures. However, no clinical studies of metal cable fixation have been reported. We hypothesised that cable fixation can provide equal stability and clinical outcome compared with Ethibond sutures. METHODS: Between 2007 and 2008, we treated 42 patients of adult type III tibial eminence avulsion fractures. Twenty-three patients were male, and 19 were female. All patients were confirmed by radiographs, MRI, and arthroscopy during surgery. Ligament injury and meniscus tears were excluded from this study. Twenty-two patients were treated with No. 2 Ethibond suture fixation (group I), and 20 were treated with cable fixation under arthroscopy (group II). Follow-up assessments included imaging evaluation, Lysholm knee score, International Knee Documentation Committee (IKDC) classification, and the Lachman test. RESULTS: Bone union was found in radiographic evaluation in all patients within 3 months. At the last follow-up, there was neither extension nor flexion limitation in any patient. There were no significant differences in the Lysholm score between the two groups at follow-up. All 42 patients were classified by the IKDC as normal or nearly normal. Stability based on the Lachman test showed two patients of grade II laxity in group I. At the final follow-up, all 42 patients had returned to their pre-injury activities. CONCLUSIONS: Cable fixation to treat type III tibial eminence avulsion fracture can provide a clinical outcome equal to that of Ethibond sutures. LEVEL OF EVIDENCE: IV. PMID- 22072326 TI - Transfusion drains versus suction drains in total knee replacement: meta analysis. AB - PURPOSE: The use of autologous blood transfusion drains in orthopaedic surgery has been the subject of debate for several years. The aim of this meta-analysis was to review the use of autologous blood transfusion drains in total knee replacement. METHODS: The primary outcomes were as follows: the number of patients requiring homologous blood transfusion, pre-operative haemoglobin and post-operative haemoglobin days 5-7. The secondary outcome measures for the meta analysis were drainage volume, length of hospital stay, average number of units transfused per patient, post-operative wound infection, and deep vein thrombosis. RESULTS: Eight randomised controlled trials met the inclusion criteria and were included in this analysis. Autologous transfusion drains were associated with a decrease in the number of patients requiring post-operative blood transfusion (pooled odds ratio = 0.36, 95% CI = 0.15-0.85, P = 0.02), the number of units transfused per patient (weighted mean difference = -0.84 (95% CI = -1.13 to 0.56), P < 0.0001), and length of hospital stay (weighted mean difference = -0.25 (95% CI = -0.48 to -0.01), P = 0.04). CONCLUSION: The results of our study highlight both likely clinical and economic benefits within total knee replacement surgery. The clinical benefits of autologous transfusion drains in the total knee replacement surgery suggested by this meta-analysis include a reduced requirement for post-operative blood transfusion and a shorter length of hospital stay. However, further large-scale high-powered randomized controlled trials are recommended to further elucidate subtle effects of autologous drains on post-operative outcome following total knee replacement. LEVEL OF EVIDENCE: II. PMID- 22072328 TI - Genome-wide expression and copy number analysis identifies driver genes in gingivobuccal cancers. AB - The molecular mechanisms contributing to the development and progression of gingivobuccal complex (GBC) cancers-a sub-site of oral cancer, comprising the buccal mucosa, the gingivobuccal sulcus, the lower gingival region, and the retromolar trigone-remain poorly understood. Identifying the GBC cancer-related gene expression signature and the driver genes residing on the altered chromosomal regions is critical for understanding the molecular basis of its pathogenesis. Genome-wide expression profiling of 27 GBC cancers with known chromosomal alterations was performed to reveal differentially expressed genes. Putative driver genes were identified by integrating copy number and gene expression data. A total of 315 genes were found differentially expressed (P <= 0.05, logFC > 2.0) of which 11 genes were validated by real-time quantitative reverse transcriptase-PCR (qRT-PCR) in tumors (n = 57) and normal GBC tissues (n = 18). Overexpression of LY6K, in chromosome band 8q24.3, was validated by immunohistochemical (IHC) analysis. We found that 78.5% (2,417/3,079) of the genes located in regions of recurrent chromosomal alterations show copy number dependent expression indicating that copy number alteration has a direct effect on global gene expression. The integrative analysis revealed BIRC3 in 11q22.2 as a candidate driver gene associated with poor clinical outcome. Our study identified previously unreported differentially expressed genes in a homogeneous subtype of oral cancer and the candidate driver genes that may contribute to the development and progression of the disease. (c) 2011 Wiley Periodicals, Inc. PMID- 22072329 TI - Contrasting DNA damage checkpoint responses in epithelium of the human seminal vesicle and prostate. AB - BACKGROUND: Prostate and seminal vesicle are two similar hormone responsive human organs that differ dramatically in their cancer incidence. DNA damage response (DDR) is required for maintenance of genomic integrity. METHODS: In this study we investigated the DDR and cell cycle checkpoint activation of these organs using orthotopic cultures of human surgery-derived tissues and primary cultures of isolated prostate and seminal vesicle cells. RESULTS: We find that the activation of ATM signaling pathway by ionizing radiation (IR) was comparable in both tissues. Previously, we have shown that the prostate secretory cells express low levels of histone variant H2AX and phosphorylated H2AX (gammaH2AX) after IR. Here we demonstrate that H2AX levels are low also in the secretory seminal vesicle cells suggesting that this is a common phenotype of postmitotic cells. We consequently established primary epithelial cell cultures from both organs to compare their DDR. Interestingly, contrary to human prostate epithelial cells (HPEC), primary seminal vesicle epithelial cells (HSVEC) displayed effective cell cycle checkpoints after IR and expressed higher levels of Wee1A checkpoint kinase. Furthermore, HSVEC but not HPEC cells were able to activate p53 and to induce p21 cell cycle inhibitor. DISCUSSION: Our results show that during replication, the checkpoint enforcement is more proficient in the seminal vesicle than in the prostate epithelium cells. This indicates a more stringent enforcement of DDR in replicating seminal vesicle epithelial cells, and suggests that epithelial regeneration combined with sub-optimal checkpoint responses may contribute to high frequency of genetic lesions in the prostate epithelium. PMID- 22072330 TI - Sentinel node biopsy in head and neck desmoplastic melanoma: an analysis of 244 cases. AB - OBJECTIVES/HYPOTHESIS: Desmoplastic melanoma's low rate of sentinel lymph node (SLN) positivity and predilection for the head and neck region have led some to question the role of sentinel lymph node biopsy (SLNB) in patients with this rare histologic variant. Given desmoplastic melanoma's sarcoma-like histology and aberrant clinical behavior, we hypothesized that SLN status may not be indicative of outcomes in desmoplastic melanoma of the head neck. The objective of this study was to compare melanoma-specific survival among patients with head and neck desmoplastic melanoma based on SLN status. STUDY DESIGN: Retrospective analysis of patient data and outcomes using the Surveillance Epidemiology and End Results (SEER) database METHODS: The SEER database was queried for patients who were diagnosed with desmoplastic melanoma and underwent SLNB. Clinicopathologic data and 5-year disease-specific survival (DSS) were compared among patients with positive and negative SLNs. RESULTS: We identified 244 patients with desmoplastic melanoma of the head and neck who underwent SLNB. Of these, only nine had positive SLNs (3.69%). Among the SLN-positive patients, five (55.6%) had scalp/neck tumors, three (33.3%) had ulcerated tumors, and tumor thickness ranged from 1.7 to 8.5 mm (mean, 4.8 mm). On univariable and multivariable analysis, SLN positivity did not significantly affect DSS in head and neck desmoplastic melanoma (P=.19 and P=.48, respectively). CONCLUSIONS: Our findings provide further evidence against routine SLNB in head and neck desmoplastic melanoma by demonstrating a lack of prognostic significance related to the procedure, and by confirming a significantly low rate of SLN positivity as well. PMID- 22072331 TI - Which is the best foot to put forward in recurrent ovarian cancer? PMID- 22072332 TI - Asymmetric alpha-2-tosylethenylation of N,N-dialkyl-L-amino acid esters via the formation of non-racemic ammonium enolates. AB - Asymmetric alpha-2-tosylethenylation of (S)-2-(pyrrolidin-1-yl)propanoic acid esters was shown to produce good yields with high enantioselectivities. The reaction proceeds via the formation of a non-racemic ammonium enolate without an external source of chirality. PMID- 22072333 TI - [Nutricion Hospitalaria, certified "excellent"]. PMID- 22072335 TI - Acanthosis nigricans as an indicator of insulin resistance in Chilean adult population. AB - BACKGROUND: Insulin resistance (IR) is associated with a higher risk of multiple diseases and its early detection would allow to minimize the associated risk; the presence of acanthosis nigricans (AN) it's associated to the presence of IR. OBJECTIVE: To evaluate the sensibility and specificity of AN to diagnose IR in a group of Chilean patients. METHODS: We designed a cross-sectional study and it was included subjects that were attended at the Center for the Attention of Metabolic Diseases at the Faculty of Medicine, University of Chile. Sixty subjects (18-60 years age) were included. It was determined BMI and diagnosed AN and skin phototype; blood samples were taken and calculated the HOMA-IR. The normality of the variables where analyzed by Kolmogorov-Smirnov test. There were used chi2 and the diagnostic concordance between AN and IR was determined using the Kappa index and Pearson's correlation. Sensibility, specificity, positive and negative predictive value were calculated and accepted p<0.05. RESULTS: The IR diagnose was 67% and AN was 43%. The major proportion of subjects diagnosed as positive for IR were also positive for AN (84.6%). The sensibility of AN to find IR was an 84% and specificity was 100%. Positive and negative predictive values were 100% and 89% respectively. It was observed a positive association between BMI and HOMA-IR (r=0.674; r2=0.454; p<0.001). CONCLUSION: To detect acanthosis nigricans in Chilean population may be effective for the early diagnose of insulin resistance and, therefore, reduce the associated cost of the late treatment of glucose metabolic disturbances. PMID- 22072334 TI - [Monitoring of a protocol for the adequacy of the pharmaceutical form of the oral medication to the degree of dysphagia in patients hospitalized in an internal medicine service]. AB - INTRODUCTION: The oral route is the most convenient way of administering medication, although it may not be safe. Dysphagia is one of the factors rendering difficult a proper feeding and administration of medication. OBJECTIVES: to improve the administration of oral medication in patients with dysphagia by changing the pharmaceutical formulation of the principles prescribed to tolerable textures. METHODS: Pilot project for the application of a dysphagia protocol that included the patients admitted to the Internal Medicine Unit at Los Montalvos Center for 4 months. After detecting the suspicion of dysphagia, a dysphagia-viscosity test was applied to know the tolerated textures. Then, the pharmaceutical formulations were adapted and the manipulation instructions for the drugs were indicated for their proper administration. RESULTS: 23 out of 627 admitted patients were included, with a mean age of 85 years (sigma+/-7.4). The pathologies implicated in dysphagia were: dementia (65.2%); cerebrovascular disease (30.4%), and Parkinson's disease (4.4%). The best texture for drug intake was a "pudding" in 48.0%. 43 active ingredients were reviewed and 134 interventions were performed: in 41% of the cases, swallowing was made easier by mixing the drug with the food and in 59% water and a thickener were used. 94% of the recommendations were considered to be appropriate. CONCLUSION: the adaptation of the pharmaceutical formulations to the degree of dysphagia impacts on the improvement of healthcare quality by implementing safety in drug prescription and administration processes. PMID- 22072336 TI - Low levels of vitamin D in professional basketball players after wintertime: relationship with dietary intake of vitamin D and calcium. AB - INTRODUCTION: Although vitamin D deficiency has a high worldwide prevalence among the general population, very little is known about vitamin status in athletes. AIM: To investigate serum vitamin D (25[OH]D) levels after wintertime in male elite basketball players, and to relate these levels to the dietary intake of vitamin D and calcium. METHODS: Subjects were 21 players from the same professional Spanish team. Blood samples to assess 25(OH)D levels were collected after wintertime during the 2008/2009 (April) and 2009/2010 (March) seasons. In addition, athletes completed 4-day dietary records to estimate energy consumption and a food frequency questionnaire to determine dietary vitamin D and calcium intake. Serum 25(OH)D levels were 47.8+/-21.8 nmol/L, with twelve subjects (57%) being vitamin D deficient (<50 nmol/L). RESULTS: Vitamin D intake was 139+/-78 IU/day and calcium intake was 948+/-419 mg/day. Serum 25(OH)D levels correlated with the daily dietary intake of vitamin D (r=0.65; P=0.001) and calcium (r=0.82; P<0.001). CONCLUSION: Professional basketball players are at higher risk of hypovitaminosis D after wintertime. Adequate intake of dietary calcium and vitamin D is required if athletes are to avoid low serum 25(OH)D levels when exposure to sunlight is limited. PMID- 22072337 TI - Breakfast quality and its relationship to the prevalence of overweight and obesity in adolescents in Guadalajara (Spain). AB - INTRODUCTION: Many young people today skip the first meal of the day in order to lose weight. OBJECTIVE: To study the impact of breakfast quality and skipping breakfast on the BMI and on the prevalence of overweight and obesity. METHOD: A nutritional study was carried out on a population of 467 secondary school students (12-17 years of age) in Guadalajara, Spain based on seven-day food journal and food frequency questionnaires. Sociodemographic data were also collected. Anthropometric measurements of weight and adiposity (BMI, percentage body fat) were also taken. RESULTS: Boys aged 15-17 ate the highest proportion of full breakfasts (18.18%), compared with 4.34% for girls the same age. Inverse relationships were recorded between breakfast energy intake and the BMI (-0.1132) and between the BMI and calcium, fibre, dairy product, and cereal intake. There was practically no correlation between protein intake and the BMI. Subjects who did not eat dairy products and those who ate cooked breakfasts had the highest BMIs. CONCLUSIONS: Skipping breakfast was not an effective way to lose weight, and weight was inversely related to breakfast quality. PMID- 22072338 TI - Relation between dietary and circulating lipids in lacto-ovo vegetarians. AB - INTRODUCTION: As factors that have a positive influence on health and specifically on serum lipids and blood pressure, the nature and composition of vegetarian diets is one of the most speculated issues in nutrition. AIMS: The aim of the present study was to compare diet, lipid profile and blood pressure levels in Brazilian lacto-ovo vegetarians and non-vegetarians. METHODS: A cross sectional study was carried out involving 87 male and female adult volunteers (29 lactoovo vegetarians and 58 non-vegetarians). Two non-vegetarians were selected for each vegetarian (paired for age and gender) in order to enhance the power of the statistical tests. Mean age was 40 (13) years; 58.6% were males. RESULTS: No differences were found regarding nutritional status based on the BMI. This similarity may be explained by the similar energy intake and degrees of physical activity in both groups. Regarding blood pressure, the only difference between groups was systolic arterial pressure, which was higher among the non vegetarians. Among the intake parameters analysed, only energy intake and the intake of polyunsaturated fat were similar between groups. Mean total cholesterol and LDL were higher among non-vegetarians. Mean serum TG was higher among the vegetarians. The greater consumption of carbohydrates among the vegetarians was reflected in the higher serum triglyceride levels. CONCLUSIONS: Although all products of animal origin have a greater amount of protein, fat and saturated fatty acids, the absence of meat from the diet may have accounted for the better lipid profile among the lacto-ovo vegetarians may also stem from the high intake of fibre and antioxidants. PMID- 22072339 TI - [An inadequate intake of manganese may favour insulin resistance in girls]. AB - AIM: to study the relationship between an adequate manganese (Mn) intake and glucose, insulin levels and insulin resistance among healthy children from Madrid (Spain). MATERIALS AND METHODS: 573 schoolchildren between 8 and 13 years old were studied. Energy and nutrients intake (especially Mn) was calculated with a "3-day diet record". Mn intake was compared to Adequate Intakes (AI) for this mineral. Weight and height were measured and body mass index (BMI) calculated. Fasting glucose and insulin were determined and the HOMA index was calculated to establish the presence of insulin resistance in children. RESULTS: Girls with and inadequate intake (below the 100% of the AI value) had higher insulin and HOMA values than girls with adequate AI values (equal or higher to 100% of AI). Having in mind confounding factors (energy, carbohydrates and lipids intake, BMI and age), a significant positive correlation was found between the contribution of Mn intake to AI and HOMA levels in girls. CONCLUSION: It seems important to ensure an adequate Mn intake in girls in order to prevent insulin resistance and diabetes type 2 in the future. PMID- 22072340 TI - Central adiposity in children born small and large for gestational age. AB - OBJECTIVE: To evaluate body composition differences between children that were born small (SGA) or large for gestational age (LGA) compared with their counterparts born adequate for gestational age (AGA). METHODS: Body composition was assessed in 124 healthy Caucasian children (50% girls) aged 6-10, classified according to their birth weight for gestational age as AGA, SGA and LGA. Fat mass (FM), percentage of FM, lean mass (LM), bone mineral content (BMC) and bone mineral density were measured by dual-energy X-ray absorptiometry (DXA) in the whole body and at different body regions. RESULTS: LM (adjusted for age and sex) and total BMC (adjusted for age, sex and weight) were both significantly higher in LGA children and lower in SGA when compared with those born AGA. After adjustments for height, LM and BMC differences between groups were not significant. In SGA children, truncal (P<0.05) and abdominal fatness (P<0.01) were higher when compared with both AGA and LGA children, after adjustments for age, sex and height. There were no differences in the percentage of total and central FM between children born LGA and AGA. CONCLUSIONS: During childhood, children born SGA had higher central adiposity regardless of their body size. Children born LGA seem to have a higher body size but with harmonic body composition and adequate body fat distribution. Small size for gestational age at birth could programme excess abdominal fat deposition in children, which is a major factor for the clustering of cardiovascular disease risk factors defining the metabolic syndrome. PMID- 22072341 TI - Using of WHO guidelines for the management of severe malnutrition to cases of marasmus and kwashiorkor in a Colombia children's hospital. AB - BACKGROUND: In 2007, the Hospital Infantil Los Angeles (HILA) in Colombia implemented a slightly-modified version of the WHO guidelines for the diagnosis and management of malnutrition during childhood. OBJECTIVE: To evaluate the efficacy of the WHO-HILA protocol in children hospitalized with severe, chronic marasmus and kwashiorkor malnutrition (MS-KWK) in 2007 and 2008. MATERIAL AND METHODS: In this descriptive retrospective study the records of 100 children hospitalized with MSKWK were initially evaluated. Of these, 30 fulfilled the inclusion criteria: children of both sexes with a primary diagnosis of MS-KWK. Patients with any chronic disease liable to cause malnutrition were excluded. Anthropometric parameters, clinical signs and biochemical indicators of malnutrition were assessed upon admission and again at discharge following application of the WHO guidelines. Univariate analysis was performed for each study variable; serum hemoglobin and albumin levels on admission and at discharge were compared, and data were subjected to bivariate analysis. RESULTS: Marasmus was diagnosed in 23.3% of children, kwashiorkor in 73.3% and marasmic kwashiorkor in 3.3%. The major clinical findings were: edema (70%), emaciation (40%), "flag sign" hair (42.86%), low serum albumin (93%) and anemia (80%). Thirteen children following the WHO-HILA protocol showed a significant nutritional status improvement (p<0.05), whereas no improvement was noted in the 17 children not treated according to the protocol. CONCLUSIONS: Application of the WHO-HILA protocol was associated with reduced morbimortality in children with marasmus kwashiorkor malnutrition. Implementation of this protocol should therefore be considered in all children's hospitals in countries where this disease is prevalent. PMID- 22072342 TI - Benefits of blackberry nectar (Rubus spp.) relative to hypercholesterolemia and lipid peroxidation. AB - INTRODUCTION: In humans, the normal metabolic activity produces free radicals that constantly, along with other risk factors, including hypercholesterolemia may be responsible for the onset of degenerative diseases. Some bioactive compounds present in blackberry (Rubus spp.) have the ability to act as natural antioxidants can make the food to minimize effects on the body caused by reactive oxygen species. OBJECTIVE: This study verified the benefits of blackberry nectar through the quantification of triglycerides, total and fraction cholesterol HDL (high density lipoprotein) and LDL-cholesterol (low density lipoprotein), blood glucose and lipid peroxidation in hypercholesterolemic hamsters. METHODS: Two groups were treated with hypercholesterolemic diets (0.1% cholesterol), one of them receiving an additional 5 mL of nectar daily, and a third (control group) treated only with a standard diet. In the blood the quantification of lipids, blood glucose and lipid peroxidation was performed. In the brain, liver and small intestine the lipid peroxidation was determined and in other organs, histopathological evaluations were carried out. RESULTS: The blackberry nectar reduced the triglycerides serum levels, total cholesterol and LDL-cholesterol in hypercholesterolemic hamsters, without influencing the HDL and blood glucose concentrations. A decrease in the initiation of lipid peroxidation reactions in the blood, brain and small intestine was also observed. Only the liver showed histopathological changes (steatosis), due to excess cholesterol, with no positive influence from the nectar. PMID- 22072343 TI - Influence of omega-3 fatty acids from the flaxseed (Linum usitatissimum) on the brain development of newborn rats. AB - OBJECTIVES: The importance of essential fatty acids, in particular the omega-3 family, in the central nervous system development of newborns is well documented. The flaxseed (Linum usitatissimum) is considered one of the best vegetable sources of omega-3 fatty acids. The influence of omega-3 fatty acids from flaxseed on the brain development of newborn rats was evaluated. MATERIAL AND METHODS: Pups of the F1 generation were obtained from 18 female Wistar rats divided in 3 groups (n=6), FG: fed with diet based on Flaxseed added with casein, CG: Casein, and MCG: Modified Casein supplemented with fibers and soybean oil. Newborn pups were weighted and submitted to euthanasia; brains were collected for evaluation of weight and lipid profile through gaseous chromatography. RESULTS: Significant increase in brain weight (39%) and relative brain weight (37%) was verified in pups from mothers fed with flaxseed diet. The omega-3 (n-3) fatty acids from the flaxseed were found in abundance in the diet made with this oleaginous and also significant increase in docosahexaenoic acid (DHA) (38%), as well as in total of omega-3 (n-3) fatty acids (62%). CONCLUSION: Maternal diet of flaxseed during pregnancy influences the incorporation of omega-3 fatty acid in the composition of brain tissue, assuring a good development of this organ in newborn rats. PMID- 22072344 TI - The combination of resveratrol and CLA does not increase the delipidating effect of each molecule in 3T3-L1 adipocytes. AB - INTRODUCTION: Trans-10, cis-12 conjugated linoleic acid (CLA) and resveratrol have been shown to reduce TG content in cultured 3T3-L1 adipocyte acting on different pathways. In recent years, the method of simultaneously targeting several signal transduction pathways with multiple natural products in order to achieve additive or synergistic effects has been tested. However, the combined effect of both molecules on lipid metabolism has not been described before. OBJECTIVE: The aim of the present work was to analyze the effect of the combination of trans-10, cis-12 CLA and resveratrol on TG accumulation as well as on FAS, HSL and ATGL expression in 3T3-L1 mature adipocytes, in order to assess a potential interaction between both molecules. METHODS: For this purpose, 3T3-L1 mature adipocytes were treated with the two molecules, both separately and combined, in 10 and 100 MUM for 20 hours. TG content and FAS, ATGL and HSL expression were measured by spectrophotometry and Real Time RT-PCR respectively. RESULTS: Both doses of CLA and 100 M resveratrol decreased TG content in mature adipocytes. The combination of both molecules reduced TG accumulation to the same extent as each one separately. No change in FAS and HSL mRNA levels after CLA and resveratrol treatment was observed. ATGL was not modified by CLA but it was increased by resveratrol and by the combination. This combination did not increase the effect caused by resveratrol on its own. CONCLUSION: Lipolysis increase via ATGL is involved in the TG reduction induced by resveratrol and the combination of both molecules. The combination of these two molecules does not increase the efficacy of each molecule separately in mature adipocytes and thus it does not represent an advantage for obesity treatment or prevention. PMID- 22072345 TI - [Prevalence of nutritional overweight and obesity and hypertension as well as their relationship with anthropometric indicators in a population of students in Granada and its provinces]. AB - INTRODUCTION: Several authors have found correlations between anthropometric parameters and blood pressure levels in overweight and obese subjects. This paper is an update on the potential of these parameters as a tool for predicting cardiovascular risk. AIMS: to estimate the prevalence of overweight and obesity. Second verify the existence of a significant correlation between the main anthropometric indicators and the blood pressure levels. SAMPLE: The population consisted of 977 children and adolescents between 9 and 17 years of age belonging to 13 schools in the province of Granada and city. METHODOLOGY: anthropometric evaluation in which they were assessed six skinfolds, waist circumference, hip and determination of blood pressure in three consecutive occasions. The anthropometric assessment phase began in March 2008 lasted until April 2009. RESULTS: We found that the prevalence of overweight in girls varied between 18.3% and 32.2%. For its part, the prevalence among boys was between 10.9% and 26.1%. Regarding the prevalence of obesity, the girls had similar rates between 4.5% and 15.1%. Among boys the prevalence of obesity was similar, and found rates between 4.7% and 12.6%. Of all the parameters measured, body mass index and waist circumference were the anthropometric indicators that showed a better correlation to blood pressure. CONCLUSIONS: BMI and WC are useful anthropometric indicators to predict cardiovascular risk in non adults. PMID- 22072346 TI - [Blood pressure variability in 24 hours in obese and non-obese adolescents with breast development 4 and 5 of Tanner's criteria]. AB - OBJECTIVE: The aim of the study was to investigate the blood pressure variability during 24 h by using ambulatory blood pressure monitoring (ABPM) in a group of obese and non-obese female adolescents with breast development status 4 and 5 of Tanner's criteria. METHODS: A cross-sectional study was conducted at the Cardiovascular Research Institute, Mexico. All subjects underwent 24 h non invasive ABPM recording device. Pubertal status was determined by breast development. MEASUREMENTS: office systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). Height, weight, body mass index (BMI), waist and hip circumferences, arm circumference, waist to hip ratio (W/H), and skinfold thickness measurements: triceps, subscapular, abdominal and supraspinal. RESULTS: Fifty-nine adolescents 13-16 years old; 29 obese (BMI 31.2+/-4.0), and 30 non- obese (BMI 21.2+/-2.2). Obese vs. non-obese: Office SBP 116.9 vs. 105.9+/-9.3 mmHg (p<0.001); ABPM in 24 h: SBP 113.8+/-6.3 vs. 107.6+/-5.7 mmHg (p<0.001); diurnal SBP 117.3 mmHg vs. 111.2 mmHg (p<0.001); nocturnal SBP 105.5+/-8 vs. 99.4 mmHg; absolute variability in 24 h DBP 10.0+/-1.8 vs. 8.7+/-1.5 (p<0.003); coefficient of variation 24 h DBP 17.3+/-3 vs. 15.4+/-2.6% (p<0.05); systolic non dipper 16 (55.2%) vs. 9 (30%) (p<0.05); pulse pressure 24 h 49.3+/-8 vs. 43.5+/-9 mmHg (p<0.01). CONCLUSION: Obese adolescents are presenting changes in BP variability during 24-h in comparison with nonobese adolescents; it also includes higher pulse pressure. Thus, these can be early indicators for the development of hypertension or other cardiovascular diseases in the adult life. PMID- 22072347 TI - [Benefits of cognitive behavior therapy and acupressure therapy in obese patients: a randomized clinical trial]. AB - OBJECTIVE: The purpose of this study was to analyze change of lifestyle in obese patients with cognitive behavior therapy and acupressure. METHODS: An experimental study was performed with placebo control group. Forty patients were randomly assigned to intervention group (cognitive behaviour therapy + acupressure) and control group (information session). Outcome measure was a questionnaire for the assessment and quantification of obesity related lifestyles. Measures were performed at baseline and, after 3-months intervention. RESULTS: After 3 months of treatment, the intervention group showed significant differences (p<0.05) in weight loss, diet and physical activity. CONCLUSION: In the obese patient, cognitive behavior therapy and acupressure, it has lost at least three kilograms over three months and has changed lifestyles related to obesity. PMID- 22072348 TI - Biochemical and functional indices of malnutrition in patients with operable, non microcelullar lung cancer. AB - INTRODUCTION: The aim of this study was to assess non-microcellular lung cancer patients' nutritional status impact on psychomotor performance, muscle strength and functional activity. MATERIAL AND METHODS: The study involved 60 consecutive patients admitted to the clinic for surgical treatment due to histologically verified non-microcellular lung cancer. The patients were divided, depending on the stage of weight loss, into two groups: relatively well-nourished--29 patients and those with malnutrition--31 patients. History, physical examination, anthropometric data, biochemical parameters as well as functional tests were carefully noted. RESULTS: Patients qualified for particular groups differed significantly in age, p<0.002. Mean values of albumin, transferrin and total protein for the well nourished patients ranged within proper values. In the malnourished patients they were respectively: 34.05+/-0.27 g/l, 1.764+/-0.27 g/l, 68.90+/-6.39 g/l and the differences were statistically significant. Total loss of urea nitrogen was significantly higher in malnourished patients 13.32+/-2.92 g/l (p<0.005). The average percentage weight loss in both groups differed significantly 0.111+/-0.044 vs. 0.031+/-0.028 at p<0.0005. In the group of malnourished patients the right hand average strength was 26.52+/-8.06 kg and the left one amounted to 25.35+/-6.04 kg, The values were significantly lower than the results recorded in well nourished patients: 34.93+/-11.27 kg, 32,37+/-11.72 kg, p<0.001. The tapping test average time of the right hand was 19.24+/-4.04 vs. 16.72+/-3.06 and of the left one 19.69+/-3.59 kg vs. 17.48+/-2.79 kg and were significantly longer in patients suffering from malnutrition (p<0.01). Simple reaction times for dominating hand were longer in the group of patients with malnutrition, for the visual stimulus 0.50+/-0.08 s vs. 0.45+/-0.087 s, (p<0.05) and for auditory one 0.43+/-0.08 vs. 0.39+/-0.08 s (non significant). CONCLUSIONS: Malnutrition in the course of non-microcellular lung cancer significantly reduces psychomotor function assessed by reaction time to visual and acoustic stimuli as well as efficiency of the functional tests evaluated by tapping test and muscle strength measurement. PMID- 22072350 TI - [Weight monitoring in parenteral nutrition: from theory to practice]. AB - OBJECTIVE: To assess the usefulness of establishing a routine gravimetric as quality assurance after the development of parenteral nutrition (PN) with a gravimetric error less than +/- 5%. MATERIAL AND METHODS: Prospective study in which 5 to 8 large volume PN were weighed daily during 2 months and for 4 months all small volume PN, considering this the real weight. The theoretical weight was calculated taking into account the densities, volumes of all products used in processing and the weight of the bags used. The gravimetric error was calculated as a percentage compared to the theoretical weight. RESULTS: 168 large volume PN and 42 small volume were weighed, gravimetric errors measures were 1.42% (SD=1.31) and 1.26% (SD=0.64), with a gravimetric error less than 5% in 98,8% and 100% respectively. CONCLUSION: Establishing a routine gravimetric control is an useful strategy that can help to guarantee the quality of the PN development. PMID- 22072349 TI - [Meat and fish consumption in a high cardiovascular risk Spanish Mediterranean population]. AB - BACKGROUND: High saturated fat consumption, mostly from red meat and sausage meat has been associated with an increase in cardiovascular risk (CVR) in contrast to the effect of high fish consumption. OBJECTIVE: To get to know the frequency of meat and fish consumption in an elderly high Mediterranean population, their correlations with adherence to the Mediterranean diet (MD) and their association with intermediate CVR phenotypes. METHODS: A cross-sectional study was carried out on 945 people (67.4+/-6.2 years old) with high CVR recruited in primary care centres of Valencia, and participating in the PREDIMED study. The frequency of meat and fish consumption was determined through a validated questionnaire. We analyzed clinical, biochemical and anthropometric variables using standard methods. RESULTS: Mean red meat consumption was high (7.4+/-4.7 times/week), being higher in men than in women (P=0.031) and was associated with greater weight (P=0.001) and prevalence of obesity (P=0.025). Fish consumption was also high (4.5+/-2.6 time/week) and was associated with lower concentrations of fasting plasma glucose (P=0.016) as well as with lower prevalence of diabetes (P=0.017). CONCLUSION: Red meat consumption in this high CVR population is very high and far from the recommendations of MD, needing, therefore, to be reduced. Fish consumption is closer to the recommendations and should be maintained. PMID- 22072351 TI - [Temporomandibular joint dysfunction, disability and oral health in a community dwelling elderly population]. AB - INTRODUCTION: Temporomandibular joint dysfunction (TMD) is involved in important activities of the stomatognathic system for nutrition, such as chewing or swallowing. If the physiological tolerance of its components is exceeded, it can trigger symptoms of temporomandibular dysfunction (TMD). OBJECTIVES: To assess and relate the symptoms of TMD, functional limitations and estimates of self perceived oral health and general geriatric population in a communitydwelling elderly population. METHODS: An observational study was performed. Ninetyfour persons belonging to units of Granada Geriatric Day were assessed symptoms of TMD (Helkimo Simplified Index), pain (VAS scale), functional limitation of stomatognathic system (research diagnostic criteria for temporomandibular disorders CDI/TTM), jaw opening index, general health index (1-5) and oral health (geriatric oral health assessment). RESULTS: In the total sample, 42.7% had at least one symptom of TMD. The most common symptoms were muscular fatigue (26.6%), noise (21.3%) and TMD pain (14.9%). The most common non-specific symptoms in the symptomatic group were neck pain and nervousness. A 48.9% of the sample had functional limitation in orofacial activities. Also, there was a statistically significant association (p<0.05) between the jaw opening index and symptomatic and asymptomatic groups with TMD. CONCLUSIONS: In the group with symptoms of TMD were more common temporomandibular joint departures and pain, and they presented lower values in oral and general health self-perception. PMID- 22072352 TI - [Effect of dietary fiber in the quantitative expression of butyrate receptor GPR43 in rats colon]. AB - INTRODUCTION: Short chain fatty acids (SCFA) acetate, propionate and butyrate are the major anions produced by the bacterial fermentation of dietary fiber (DF) in colon. Recently, butyrate has been recently studied because is important to maintain colonic functions and because it has been related with a protective effect in colorectal cancer, which is mainly, explained by its potential to regulate gene expression by inhibiting enzyme histonedeacetylase (HDAC). Several investigationsshown that SCFAreceptor GPR43 is involved insignal transduction mechanisms once they bind to ligands such as butyrate to generate different physiological effects in colonocytes. OBJECTIVE: Determine if dietary fiber consumption from nopal (Opuntia ficus I.) containing a ratio of soluble-insoluble fiber 40/60, has a direct influence on the quantitative expression of butyrate specific receptor GPR43. METHODS: Wistar rats were fed with four different diets formulated at different concentrations of dietary fiber of 0, 5, 15 and 25% of dietary fiber from opuntia, respectively. RESULTS AND DISCUSSION: The results shown an increase in the expression of GPR43 (93.1%) when rats was fed with a 5% fiber diet, using beta-actin as a reference gene. The results of this investigation will contribute to determinate the relation of diet with intestinal health for the purpose of expanding the knowledge of butyric acid on colonic functions. PMID- 22072353 TI - Nutritional status of intellectual disabled persons with Down syndrome. AB - BACKGROUND: To evaluate the nutritional status in young adults with Down syndrome (DS). METHODS: 38 persons, 15 (39.5%) women and 23 (60.5%) men (age range 16-38 years) with DS. Body composition was analyzed from anthropometric parameters according to standard protocols, levels of physical activity and nutrient intake was determined using validated questionnaires: a 72 h recall and consumption food frequency questionnaire (recorded by the tutors of the participants). The following biochemical parameters were estimated: blood lipids profile (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides), glucose, uric acid, proteins (ferritin and transferrin), minerals (Fe, Zn, Cu, Mg and Se) and vitamins (B12, B9, E, C and beta-carotene). The data were statistically analysed with Student t tests. RESULTS: From the 38 participants, 36.8% were overweight (BMI: 25-29.9 kg/m2) and 36.8% were obese (BMI>=30 kg/m2). The BMI differed from women to men (P<0.001) (29.1+/-4.3 and 27.9+/-4.6 kg/m2, respectively). The average values of the biochemical parameters, except for uric acid, both in women and men were within normal ranges. The average energy intake was 1,909+/-337 and 2,260+/-284 kcal/day for women and men, respectively. The contribution of proteins to total caloric intake was 18.8 and 16.3% for women and men, respectively, while carbohydrates contributed 43.3 and 45.6%, and lipids 37.9 and 38.1%. All participants were sedentary. CONCLUSION: In this group presented a high prevalence of overweight and obesity. Further research is required in the development and evaluation of appropriate intervention programs to improve their nutritional status and quality of life. PMID- 22072354 TI - [Weight estimation in Mexican elderly outpatients from antropometric measures from the SABE Study]. AB - INTRODUCTION: The weight is an anthropometric parameter routinely used in ambulatory and hospital settings, and takes its importance, because often there are clinical conditions that impede it's taking in a traditional scale. There are equations to estimate weight. However, they have not been designed for Mexican ambulatory patients. OBJECTIVE: To develop an equation to estimate weight in Mexican ambulatory patients from the Study of Health, Well Being and Aging, corresponding to Mexico city an surrounded area. MATERIAL AND METHODS: The database of the Study of Health, Well Being and Aging of Mexico City was used, and adults of 60 years and older, who completed the anthropometric measures were included. Two groups of datasets were crated though random numbers, one for the design and the other for the validation of the equation. The equation was obtained from the first database and cross-validated in the second. RESULTS: The equations obtained were: (0.67)* (Knee height)+(0.46)* (Mid-arm circumference)+(0.60)* (waist circumference)+(0.38)* (hip circumference)+(0.53)* (calf circumference)-(0.17)* (Age in years)-80.01 and (0.69)* (Knee height)+(0.61)* (Mid-arm circumference)+(0.17)* (waist circumference)+(0.45)* (hip circumference)+(0.58)* (calf circumference)-(0.24)* (Age in years)-55.9 in men and women respectively. The correlation coefficients were 0.94 y 0.92 (p<0.001 for both). The differences between the real and estimated values were not significant. CONCLUSION: The equations developed in our analysis were confident and can be employed to estimate weight in ambulatory elderly. It is needed to test its validity in clinical scenarios were it is not possible to weight patients directly in the rest of the Mexican republic and adjust to specific populations. PMID- 22072355 TI - [Evaluation of perioperative nutritional therapy in patients with gastrointestinal tract neoplasms]. AB - OBJECTIVES: Cancer is usually associated to an important level of desnutrition together with a postoperative morbidity and mortality increase. The purpose of this study was evaluating its efficacy perioperative nutritional support to reduce surgical complications, stances and mortality significantly in patients undergoing higher digestive tract procedures. METHOD: A prospective, randomized trial was done among a sample of neoplasic patients undergoing higher intestinal tract resective surgery during a period of 4 years. After a nutritional assessment, a perioperative immune-enhancing formula was randomly assigned to a group of patients who presented malnourished preoperatively (DS) while well nourished and the rest of malnourished patients (DNS) received pre-surgical dietetic guidance and intravenous fluids after surgery until the reintroduction of normal diet. The variables studied were: age, sex, tumor stage and length of hospital stay. Nutritional status at admission and discharge, mortality, outcome from surgery and gastrointestinal side effects (tolerability, diarrhoea, vomits or distension) were also collected. Statistical analyses were performed with the with the chi2 for qualitative variables, ANOVA and the Turkey post-hoc tests for the quantitative ones, with a significance of 95%. RESULTS: Sample conformed by 50 patients in 3 groups that were compared for all baseline and surgical characteristics. Significant differences were observed in the incidence of gastrointestinal and infectius complications with better progress in DS group. It was obtained a reduction in the length of hospital stay in 12.29 days in DS group in contrast to DNS group (P=0.224). CONCLUSIONS: Significant benefit from perioperative nutritional support has been demonstrated in severely malnourished patients undergoing major surgery. A statistically significant decrease in the incidence of postoperative gastrointestinal symptoms, a reduction in the length of hospital stay and less morbidity occurred on the group that received perioperative nutrition. PMID- 22072356 TI - [Assessment of the nutritional status of a group of people older than 50 years by means of dietary and body composition parameters]. AB - OBJECTIVE: To assess the nutritional status of elder adults by means of dietary and body composition parameters. METHODOLOGY: The sample comprised 49 adults, older than 50 years (23 men and 26 women) with a mean age of 54.84+/-4.56 years, working at a private university. The body composition was analyzed by using anthropometric parameters. The energy and nutrients intake was gathered by means of a registry of all the foods and beverages consumed during 3 days that was filled-up by each (previously instructed) participant and estimating the amounts through photographic models. Total energy requirements were estimated by the Harris-Benedict and FAO/WHO calculations. RESULTS: The body mass index was similar (p=0.018) in both men and women (26.1+/-1.9 and 24.4+/-2.8 kg/m2). The percentage of fat obtained by anthropometrics was 29.6+/-3.6 and 36.8+/-3.1% (p=0.000) in men and women, respectively. The level of physical activity was very light to light. Daily energy intake was appropriate for total energy demands when these were calculated by the calculations proposed by FAO/WHO. The caloric profile indicated an unbalance with high proteins and lipids and low carbohydrates intake. As for the micronutrients, the diets assessed indicated a deficient intake of folic acid and vitamins D and E, in both genders, and zinc and selenium also in women. CONCLUSIONS AND RECOMMENDATIONS: We have found overweight problems according to the BMI and the waist circumference, and obesity according to the body fat percentage, with the potential risk for the development of an associated complication. It would be advisable to improve the quality of the diets consumed by increasing the amount of some micronutrients and fiber, and by promoting an increase in the physical activity. PMID- 22072357 TI - Hematologic and immunological indicators are altered by chronic intake of flaxseed in Wistar rats. AB - This work sought to evaluate the effects of chronic intake of flaxseed upon hematologic parameters and immunological findings on body development of Wistar rats. Female Wistar rats were used after gestation. They were randomly assigned into two groups during lactation period: Control group (CG), fed with casein based diet, made up of 17% protein and flaxseed group (FG), fed with casein based diet with the addition of 25% flaxseed. At weaning, 12 male pups of each group continued to receive the experimental diets of their mothers (with only 10% of protein) until adult age, when they were killed at 250 days of life aiming at blood collection. At 250 days old FG presented significant reduction in body mass (p<0.000) and higher levels of hemoglobin (p=0.019) and albumin (p=0.030) than CG. It was observed smaller percentage of segmented lymphocytes (p=0.016) in rats from FG and bigger percentage of segmented leucocytes (p=0.023) when compared to CG. The chronic consumption of flaxseed altered hematologic and immunological indicators in adult Wistar rats. Supplementation with flaxseed seems to be beneficial to maintenance or reduction of body mass. PMID- 22072358 TI - [Impact of consumption of corn flour with low level enrichment in children of rural zones]. AB - INTRODUCTION: Corn has been from the prehispanic era, the most important feeding plant in the Mexican population, particularly in the most important sectors and in marginal areas. In this setting, enriching the product as flour implies an increase in its nutritional quality, especially because corn is the basic food. OBJECTIVE: To assess the effect of the consumption of corn flour enriched with 3% soybean, vitamins, and minerals on the growth and development of infants and preschool children. MATERIAL AND METHODS: experimental study lasting 10 months. The experimental group (n=195) received enriched corn flour whereas the control group (n=200) received non-enriched flour. The indicators were: nutritional status, mental and psychomotor development, and blood hemoglobin levels. RESULTS: in the total sample, there were no differences between the experimental group and the control group. However, there were improvements in the weight-to-height and weight-to-age indexes in the children consuming enriched flour and in children older than one year, who were the babies of indigenous women living in marginal areas. CONCLUSIONS: enriched corn flour appears to be an alternative benefitting the children population with higher nutritional deficiencies. However, a longer intervention is necessary to obtain better results. PMID- 22072359 TI - Influence of physical activity and dietary habits on lipid profile, blood pressure and BMI in subjects with metabolic syndrome. AB - BACKGROUND: The present study was determined the influence of physical activity and dietary habits on lipid profile, blood pressure (BP) and body mass index (BMI) in subjects with metabolic syndrome (MS). AIMS: Identify the relationship between physical activity and proper nutrition and the probability of suffering from myocardial infarction (MI). METHODS: Hundred chronically ill with MS who were active and followed a healthy diet were classified as compliant, while the remaining subjects were classified as non-compliant. RESULTS: The compliant subjects show lower BMI values (30.8+/-4.9 vs 32.5+/-4.6), as well as lower levels of triacylglycerol (130.4+/-48.2 vs 242.1+/-90.1), total cholesterol (193.5+/-39 vs 220.2+/-52.3) and low-density lipoprotein cholesterol (105.2+/ 38.3 vs 139.2+/-45). They show higher values in terms of high-density lipoprotein cholesterol levels (62.2+/-20.1 vs 36.6+/-15.3), with statistically significant differences. In terms of both systolic and diastolic pressure, no differences were revealed between the groups; however, those who maintain proper dietary habits show lower systolic blood pressure levels than the inactive subjects. The probability of suffering from MI greatly increases among the group of non compliant subjects. CONCLUSIONS: Our results demonstrate how performing aerobic physical activity and following an individualized, Mediterranean diet significantly reduces MS indicators and the chances of suffering from MI. PMID- 22072360 TI - Influence of fat intake on body composition, lipemia and glycemia of type 1 diabetics. AB - BACKGROUND: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia and body composition is important in the disease control. The nutritional intervention has relevance in the improvement of glycemia and lipemia in diabetic patients. AIM: Evaluate the influence of fat intake on body composition, lipemia and glycemia on patients with type 1 diabetes mellitus. METHODS: 19 patients were evaluated by anthropometric (body mass index and waist circumference), body composition (fat mass, lean body mass and total body water by bioelectrical impedance) and biochemical variables, after 8 hours of fasting. Dietary assessment was performed using the dietary records for 3 days, analyzed for nutritional software DietPro 5i. The groups were formed according to the usual intake of saturated fatty acids (SFA) (G1<10% of total energy expenditure (TEE) of SFA and G2>=10% of TEE of SFA). Statistical analysis was performed in SPSS 16.0, considering p<0.05. RESULTS: There was no difference in anthropometric and biochemical variables between groups, but G1 presented higher fat mass (FM) and G2 high SFA and adequate mounsaturated fatty acids (MUFA) intake. The lipemia and glycemia were not affected by high SFA intake, but adequate MUFA intake may have influenced the results of these variables. No found relation between type of fat ingested and biochemistry variables. CONCLUSION: Body composition can be influenced by type of fat ingested. Lipemia and glycemia were not influenced by high SFA intake, perhaps due to MUFA intake adequate. PMID- 22072361 TI - Inflammatory mediators and immune response in Mexican adolescents. AB - INTRODUCTION: Low-grade inflammation and increased immunity related to cardiovascular diseases have been described in children and adults, however, studies in Mexican adolescents are being done at present. OBJECTIVE: To evaluate inflammatory proteins and indicators of immunity in adolescents by gender and body mass index. MATERIAL AND METHODS: 115 Mexican adolescents, 15-18 years old (36 men), were divided into non-overweight, risk of overweight and overweight by CDC pediatric criteria by body mass index. Serum concentrations of ceruloplasmin, C3 and C4 were quantified by nephelometry; IL-6 and TNF-alpha from stimulated supernatant were analyzed with Human Th1-Th2 cytokine CBA II kit (BD Biosciences Pharmigen, San Diego, CA), and detected by flow cytometry. Data were analysed by Mann-Whitney U. RESULTS: Gender differences were found in C3 (men: median 118.8, mean rank: 41.0; women: median: 143.9, mean rank: 65.7, p=0.001) and ceruloplasmin (men: median: 31.01, mean rank: 47.06; women: median: 31.0, mean rank: 62.9, p=0.015). Differences by BMI were found in C3 (women non-overweight: median: 137.00 mena rank: 36.52; women with risk of overweight/overweight: median: 175.80, mean rank: 57.69, p=0.002) and C4 (men non-overweight: median: 23.40, mean rank: 16.60; men with risk of overweight/overweight: median: 26.40, mean rank: 26.36, p=0.028; women non-overweight: median: 24.25, mean rank: 37.16 and women with risk of overweight/overweight: median: 32.80, mean rank: 54.42, p=0.013). CONCLUSION: Inflammatory proteins are increased in adolescents with risk of overweight and overweight, particularly in women. PMID- 22072362 TI - Enteral or parenteral nutrition in traumatic brain injury: a prospective randomised trial. AB - INTRODUCTION: Few studies have evaluated the route of nutritional therapy in patients with head trauma. OBJECTIVE: We aimed at investigating whether early enteral (EN) or parenteral nutrition (TPN) may differ in protein/ calorie supply, serum glucose modifications, and acute phase response in patients with traumatic brain injury (TBI). METHODS: Twenty two patients with moderate TBI (Glasgow score between 9-12) were randomized to receive isocaloric and isonitrogeneous either EN (n=12) or TPN (n=10). The daily amount of calories and nitrogen (N) supplied, the nitrogen balance, and the daily serum level of glucose, C-reactive protein, and albumin were collected for 5 consecutive days. Clinical endpoints as length of stay and mortality were also compared. RESULTS: Mortality was 9.1% (two cases) with one case in each group. A progressive caloric deficit occurred in both groups (p=0.001) without difference between them. The mean serum glucose level in TNP patients (134.4, 95% CI=122.6 to 146.2 mg/dl) was significantly higher than in the EN group (102,4; 95% CI 91.6 to 113.2 mg/dL) (p<0.001). There was a trend (p=0.06) of 24 h urinary N loss to be greater in TPN group which received higher amounts of N than the NE group (p<0.05). However, nitrogen balance was similar in the two groups. There was no difference in either the clinical outcome variables or the acute phase response. CONCLUSION: Both routes were able to supply increasing provision of calories to brain injured patients. TPN provided significantly greater amount of nitrogen but losses were also greater. Nitrogen balance was similar with both types of therapy. Parenteral compared to enteral nutrition lead to greater hyperglycemia. There was no influence of the route in both the early inflammatory response and clinical outcome. PMID- 22072363 TI - Sagital abdominal diameter, but not waist circumference is strongly associated with glycemia, triacilglycerols and HDL-C levels in overweight adults. AB - AIM: To correlate the sagittal abdominal diameter (SAD) and waist circumference (WC) with metabolic syndrome-associated abnormalities in adults. METHODS: This cross-sectional study included onehundred twelve adults (M=27, F=85) aging 54.0+/ 11.2 yrs and average body mass index (BMI) of 30.5+/-9.0 kg/m2. The assessment included blood pressure, plasma and anthropometric measurements. RESULTS: In both men and female, SAD and WC were associated positively with body fat% (r=0.53 vs r=0.55), uric acid (r=0.45 vs r=0.45), us-PCR (r=0.50 vs r=0.44), insulin (r=0.89 vs r=0.75), insulin resistance HOMA-IR (r=0.86 vs r=0.65), LDL-ox (r=0.51 vs r=0.28), GGT (r=0.70 vs r=0.61), and diastolic blood pressure (r=0.35 vs r=0.33), and negatively with insulin sensibility QUICKI (r=-0.89 vs r=-0.82) and total cholesterol/TG ratio (r=-0.40 vs r=-0.22). Glycemia, TG, and HDL-c were associated significantly only with SAD (r=0.31; r = 39, r=-0.43, respectively). CONCLUSION: Though the SAD and WC were associated with numerous metabolic abnormalities, only SAD correlated with dyslipidemia (TG and HDL-c) and hyperglycemia (glycemia). PMID- 22072364 TI - [Study of the serum levels of leptin, ceruloplasmin and lipoprotein (a) as indicators of cardiovascular risk in a population of adolescents in Granada (Spain)]. AB - Numerous studies have focused on establishing a relation between the serum values of biomolecules such as leptin, ceruloplasmin, and lipoprotein (a), and the nutritional state and levels of diastolic and systolic blood pressure in subjects with problems of overweight or obesity. However, in many cases, the results obtained have not been conclusive. The results of our study confirm the existence of a statistically significant association between the serum levels of these biomolecules, the nutritional state of the subjects, and levels of diastolic and systolic blood pressure. For the population of overweight and obese adolescents studied, the evaluation of the serum concentrations of these biomolecules was found to be an important instrument that could be used to identify those subjects with an elevated risk of suffering cardiovascular disorders basically derived from a hypertensive status. PMID- 22072365 TI - [Prevalence of malnutrition and influence of oral nutritional supplementation on nutritional status in institutionalized elderly]. AB - BACKGROUND: Nutritional supplementation might be an effective strategy for improving the nutritional status and the quality of life of institutionalized fragile elderly. OBJECTIVES: The prevalence of malnutrition and its relation with disease, and the influence of dietary supplementation by means of oral formulas on the nutritional status of elderly nursing home residents were assessed. METHODS: Two studies were carried out, one a cross-sectional survey in 31 subjects and the other a longitudinal-sectional survey in 19 subjects, both groups living in a public nursing home in the city of Murcia (SE Spain). Body mass index (BMI), serum albumin concentration (ALB) and geriatric nutritional risk index (GNRI) were assessed as markers of potential malnutrition. Illnesses were ascertained from medical records. RESULTS AND DISCUSSION: The prevalence of malnutrition of the total collective was high (39%), and especially in the fragile subjects (50%). The administration of oral nutritional supplements in the usual diet for 12 months significantly increased ALB and GNRI, and had no effect on body weigh and BMI. Jointly, these effects decreased the in the number of subjects at high nutritional risk and increased the number of subjects with a low or zero risk of malnutrition. CONCLUSION: The administration of oral nutritional supplements in the usual diet of this elderly collective is an effective clinical strategy in nutritional therapy. PMID- 22072366 TI - Altered membrane lipid dynamics and chemoprevention by non-steroidal anti inflammatory drugs during colon carcinogenesis. AB - The present work focuses on the anti-neoplastic role of non steroidal anti inflammatory drugs (NSAIDs) in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH) induced carcinogenesis. The steady-state fluorescence polarization technique was applied to assess membrane fluidity, membrane polarity and lipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treatment indicates more fluidity associated with carcinogenesis. The DMH group had shown lower order parameter indicating more fluidity whereas NSAIDs resulted in increasing the membrane lipid order. The converging effects of these changes were more in membrane phase separations and membrane phase state. In DMH treatment membrane shows lesser phase separation or high polarity, and more liquid crystalline state while for NSAID groups membranes have higher phase separations or low polarity, and more of the gel phase. Further, NSAIDs induced anti-proliferative effects were evidently observed by apoptosis in the colonocytes by using acridine orange-ethidium bromide fluorescent staining and Terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The results suggest that NSAIDs induced alteration in the membrane biophysical parameters may be an important initiating event for the chemopreventive action. PMID- 22072367 TI - Impact of two low-calorie meals with and without bread on the sensation of hunger, satiety and amount of food consumed. AB - BACKGROUND: The aim was to compare the differences in feelings of hunger and satiety in a group of overweight/obese women after eating a test meal with or without bread. PATIENTS AND METHODS: The study included 122 women (BMI>=25<40 kg/m2) who were randomly assigned to consume one of the following test meals: NO BREAD meal (2.40 MJ, 46% carbohydrates, 26% protein, 28% fat; which included rice or pasta) and BREAD meal (2.39 MJ, with equal caloric distribution and the same foods except with bread instead of rice or pasta). A visual analogue scale (VAS) was used, with 5 questions to be answered at different times: 1) just before eating, 2) just after eating and exactly 3) 60 and 4) 90 minutes after eating the test meal. The test was performed at the start and after 16 weeks of following a lifestyle modification program based on a low-calorie diet (with or without bread). RESULTS: 104 women completed the study (48.4+/-9.0 years) with a baseline BMI of 29.8+/-3.5 kg/m2. At the start of the study there were no significant differences in any of the VAS parameters measured between the groups. After 16 weeks, BREAD group obtained higher scores in question 3 (referring to the sensation of satiety) that were significant at time 3 (7 versus 5; p<0.05) and time 4 (8 versus 4; p<0.01). CONCLUSIONS: The inclusion of bread in a low-calorie meal may result in a greater sensation of satiety after eating. These results contradict the recommendation to exclude bread from a food plan aimed at weight loss. PMID- 22072368 TI - [Performance of nutritional education programmes to prevent obesity in children through a pilot study in Soria]. AB - BACKGROUND: Spain has one of the highest rates of childhood obesity in Europe. The Spanish authorities of health have launched some strategies, which among others, includes activities to develop healthier dietary habits in children. OBJECTIVE: The aim of the present study has been to assess the effectiveness of the nutritional education programmes undertaken to prevent obesity in children through a pilot study in Soria. This has been evaluated through the comparative study of adherence to the Mediterranean Diet and anthropometric parameters between two samples of same age schoolchildren at an interval of 10 years. SUBJECTS AND METHODS: Adherence to the Mediterranean diet and BMI was evaluated in two occasional samples of pupils aged between 6 and 9 years, who were attended to 5 public Schools in Soria, during two academic years 1998/ 99 (n=119) and 2008/09 (n=231). Adherence to the Mediterranean diet was evaluated by the KidMed index. RESULTS: There were no differences in KidMed score between sexes within the same sample. However, there were a significant differences (p<0.0001) in total KidMed socore between the 2008/09 and 1998/99 schoolchildren. The mean BMIs were similar for the boys and girls of the same course, while it was significantly lower (p<0.05) in 2008/09 school children. The Kidmed score was negatively associated with BMI (r=-0.133, p<0.05). CONCLUSIONS: The proportion of childhood that showed an upper-middle degree of adherence to the Mediterranean diet patterns was higher among 2008-09 pupils. These results suggests that activities coordinated from different agencies in Spain, may be a useful tool for promotion of healthy eating habits in children. PMID- 22072369 TI - Prevalence of protein supplement use at gyms. AB - At the present time, the abuse of all class of sport nutritional supplements (NS) has extended the people who go regularly to gymnasiums. Between these substances there are the Protein Powder Supplements (PPS). The purpose of this study is to examine the consumption of PPS in 415 individuals from Seville fitness centers. All individuals were evaluated with anthropometric measurements and completed a questionnaire previously reviewed, evaluating the validity of the content, application, structure and presentation. 28% of the individuals were using or used PPS. Of the total, 42.7% of male individuals compared to 3.2% of the females. The use of PPS was higher than what has been reported in previous studies about supplement use in fitness center, 28% vs 10-14% aprox. The SPP use is associated with sex, age, and time of sport practiced. More than a 25% of the total individuals that attend a gym use PPS. The total individuals that attend a gym and use PPS far exceed the RDA of protein for general population and/or athletes, being able to cause problems of health. PMID- 22072370 TI - Food habits and nutritional status of elderly people living in a Spanish Mediterranean city. AB - AIMS: The aim of this study was to assess the food habits and nutritional status of free-living, non-institutionalised, elderly people of Torrevieja, a Spanish city located in the Mediterranean coast. METHODS: Anthropometric and dietary survey (two 24 hour recalls) were assessed in 200 (83 men and 117 women) free living elderly people (average age 72.3+/-6.6 years). RESULTS: Just married women accomplished the recommended energy intake. The contribution of macronutrients to the total energy intake was different from the Recommended Intake for the elderly, since it was too derived from proteins, fats, SFA and sugars, but in only small amounts was derived from complex carbohydrates. High percentages of elderly persons showed inadequate intake of calcium, zinc, magnesium, potassium, copper, iodine, folic acid, vitamin A, vitamin D, vitamin E, and riboflavin. Men showed lower micronutrient intake than women. CONCLUSIONS: An increase in dietary complex carbohydrate, and a decrease in protein and fats, especially SFA, is recommended. It would be desirable to increase the consumption of fruits, vegetables, whole cereals, fish and skimmed dairy products. PMID- 22072371 TI - [Nutritional profile of foods offered and dietary intake in school canteens in Biscay]. AB - INTRODUCTION: Nowadays the school canteen occupies a central place in the supply and in the nutritional education of the children in school age. OBJECTIVES: To assess the nutritional adequacy of the school menus and the food intake of the children. METHODS: 1,500 trays were selected in six school dining rooms of Biscay. Dietary intake was evaluated by means of the technique of double weighed and visual estimation of the residues. RESULTS: Evaluation of the menus: Macronutrients: carbohydrates 48%, proteins 20%, lipids 32%. Weekly offer: The first plate: vegetables 1.1; legumes 1.8; potatoes 0.4; pasta-rice 1.7. The second plate: meat 2.5; fish 1.4; eggs 0.6; precooked fried food 0.5. Garnish: potatoes 0.5; sauces 0.8; lettuce 1.7; cooked vegetables 1; no garnish 1. Dessert: fruit 2.8; dairy product 2; other 0.2. Significant changes have been observed in 4% of the menus. The vegetable garnish is not served in 40% of the occasions. 70% do not eat the vegetable garnish. CONCLUSIONS: Though the theoretical offer of vegetables is appropriate, due to the fact that frequently the vegetables are not served in garnish and to that when they are served children do not eat them, their final intake is poor. The protein contribution to the diet is higher than the recommended. Meaningful changes take place often in the composition of the menus. PMID- 22072372 TI - Fitness, fatness and cardiovascular profile in South Spanish and North Moroccan women. AB - INTRODUCTION: We studied the differences on physical fitness, fatness and cardiovascular profile in Spanish and Moroccan women. MATERIAL AND METHODS: The study comprised 63 and 58 women aged 45-65 years from South of Spain and North of Morocco, respectively. We assessed fitness and body composition using standard procedures. We also assessed resting heart rate (RHR), blood pressure, fasting glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. RESULTS AND DISCUSSION: Moroccan women had a better performance in the main health-related physical fitness components, i.e. higher levels of cardiorespiratory fitness (P=0.01) and (lower-body) muscular strength (P<0.001). Diastolic blood pressure (P=0.004), RHR and total cholesterol (both P=0.04) were lower in Moroccan women. No differences were observed in the prevalence of metabolic syndrome. CONCLUSIONS: The women from Morocco had a healthier fitness and cardiovascular profile than the women from Spain. Further research on physical fitness and other health indicators in understudied populations is needed. PMID- 22072373 TI - [What do people know and perceive about salt consumption and its impact on health?]. PMID- 22072374 TI - Assessment of actual food portions sizes in a sample of adolescents from Cochabamba (Bolivia). PMID- 22072375 TI - [Final report on evaluation of scientific journals]. PMID- 22072376 TI - Expression of Stat3 and indoleamine 2, 3-dioxygenase in cornea keratocytes as factor of ocular immune privilege. AB - PURPOSE: Ocular immune privilege is a multifactorial phenomenon evolutionally selected to prevent immunogenic inflammation from disrupting the visual axis and causing blindness. Here, we investigated the role of signal transducers and activators of transcription (Stat3) and indoleamine 2,3-dioxygenase (IDO) in ocular immune privilege in corneal stromal cells. METHODS: Human keratocytes were isolated and cultured in vitro, and Stat3 and IDO expression on keratocytes was investigated by reverse transcription polymerase chain reaction (RT-PCR). The active form of Stat3 was detected by flow-cytometry, and IDO enzyme activity following IFN-gamma stimulation of keratocytes was measured by tryptophan to kynurenine conversion with photometric determination of kynurenine concentration in the supernatant. RESULTS: Stat3 was constitutively expressed in cultured keratocytes and up-regulated following IFN-gamma stimulation. The active form of Stat3 was also up-regulated following IFN-gamma stimulation. IDO expression and enzyme activity was markedly induced following IFN-gamma stimulation, but this induction was prevented by the IDO specific inhibitor, 1-methyl tryptophan (1 MT). CONCLUSIONS: On the basis of this study, Stat3 and IDO may act as a factor of ocular immune privilege in corneal keratocytes. Thus, focus on these inhibitory molecules should be considered in studies aimed at developing therapeutic agents for controlling ocular inflammatory or immune diseases. PMID- 22072377 TI - Intravitreal treatment with antisense oligonucleotides targeting tumor necrosis factor-alpha in murine herpes simplex virus type 1 retinitis. AB - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine known to participate in intraocular inflammatory disease. This study investigated whether treatment with intravitreal antisense-oligonucleotides (ASON) targeting TNF-alpha mRNA affects the progression of herpes simplex virus 1 (HSV-1) retinitis in mice. METHODS: The in vivo uptake of the oligonucleotid after intravitreal injection was determined with FITC-labeled TNF-alpha ASON. HSV retinitis was induced on day 0 by the injection of HSV-1 (KOS strain) into the anterior chamber (AC) of the right eyes of BALB/c mice (von Szily model). The left contralateral eyes were injected intravitreally on day 7 with TNF-alpha ASON, sequence-unspecific control ASON (CON), or buffer. The clinical course of retinitis, ocular inflammatory cell-infiltration, TNF-alpha expression in the eye by ELISA, delayed-type hypersensitivity (DTH) reaction, virus-neutralizing antibody titers in the serum, uptake of [3H]thymidine from regional lymph node (rln) cells, and viral content in the eyes were determined. RESULTS: In vivo, strong fluorescence of FITC- TNF-alpha ASON was detected in the choroid and retina up to 3 days after intravitreal injection, but none in the rln. After treatment of eyes with ASON, decreased expression of TNF-alpha in the eye, and reduced incidence and severity of retinitis on day 10 after infection (P < 0.05) could be found. The other parameters were not significantly influenced after TNF alpha ASON treatment. CONCLUSIONS: TNF-alpha participates in the pathology of HSV 1 retinitis. Local inhibition of TNF-alpha mRNA by intraocular TNF-alpha ASON injection did not influence the systemic HSV-specific immune response or the antiviral response in the eye, but reduced ocular inflammatory bystander damage. PMID- 22072379 TI - Conformational and stereoelectronic investigation of tryptamine. An AIM/NBO study. AB - Due to the free radical scavenger properties of Tryptamine (TRA), as well as of others indole derivatives, it is in our interest to explore deeply the stereoelectronic aspects that would be relevant in their stabilization and antioxidant activity. In this work the conformational space of TRA was scanned using molecular dynamics complemented with functional density calculations at B3LYP/6-31 + G** level. Twenty one conformers of lowest energy were obtained, their electronic distributions were analyzed at a higher calculation level, thus improving the basis set (B3LYP/6-311++G**). A topological study based on Bader's theory ( AIM: atoms in molecules) and natural bond orbital (NBO) framework was performed. The study was enriched by a deep analysis of maps of molecular electrostatic potential (MEP) through a coordinated NBO/AIM analysis. The conformational preferences were explained by hyperconjugative interactions, which were revealed by NBO data. Because radical scavenging by indolic compounds is strongly modulated by their functional residues our study was related to similar analysis done previously on Indole and 1H-indole-3-acetic acid (IAA). Therefore, the conformational space of TRA was studied from a new perspective focusing on a deep analysis of the geometric and electronic properties of TRA conformers. The changes of the electronic distribution introduced by the substituent and the conformational flexibility of the side chain were addressed. The results reported contribute to the understanding of the structure, stability and reactivity of TRA and others indole derivatives. PMID- 22072378 TI - Astaxanthin increases choroidal blood flow velocity. AB - PURPOSE: Previous studies have reported that astaxanthin (AXT) has antioxidative and anti-inflammatory effects in addition to its ability to shorten blood transit times. As laser speckle flowgraphy (LSFG) can noninvasively visualize the hemodynamics of the choroidal circulation, we used the technique to evaluate whether continuous ingestion of 12 mg of AXT per day could increase quantitative blood flow velocity. METHODS: In this randomized, double-blind, placebo controlled study, we examined 20 healthy volunteers who ingested 12 mg AXT or placebo capsules over a 4-week period. LSFG was measured in the right eyes of all subjects at pre-ingestion, and at 2 and 4 weeks after the treatment of AXT. LSFG values were used to calculate the square blur rate (SBR), which is a quantitative index of relative blood flow velocity. RESULTS: A significant increase of the macular SBR was seen 4 weeks after AXT ingestion when compared to the pre ingestion values (Wilcoxon signed-rank test, P = 0.018). In contrast, no statistical difference in the macular SBR was detected in the placebo group (Friedman test, P = 0.598). No subjective or objective adverse events were found after the 12-mg AXT ingestion. CONCLUSIONS: Results suggest that administration of AXT over a 4-week period can elevate the choroidal blood flow velocity without any adverse effects. PMID- 22072380 TI - [MRSA & Co.: Spread of new "superbugs"]. PMID- 22072381 TI - Identification of a microglia phenotype supportive of remyelination. AB - In multiple sclerosis, endogenous oligodendrocyte precursor cells (OPCs) attempt to remyelinate areas of myelin damage. During disease progression, however, these attempts fail. It has been suggested that modulating the inflammatory environment of the lesion might provide a promising therapeutic approach to promote endogenous remyelination. Microglia are known to play a central role in neuroinflammatory processes. To investigate the microglia phenotype that supports remyelination, we performed genome-wide gene expression analysis of microglia from the corpus callosum during demyelination and remyelination in the mouse cuprizone model, in which remyelination spontaneously occurs after an episode of toxin-induced primary demyelination. We provide evidence for the existence of a microglia phenotype that supports remyelination already at the onset of demyelination and persists throughout the remyelination process. Our data show that microglia are involved in the phagocytosis of myelin debris and apoptotic cells during demyelination. Furthermore, they express a cytokine and chemokine repertoire enabling them to activate and recruit endogenous OPCs to the lesion site and deliver trophic support during remyelination. This study not only provides a detailed transcriptomic analysis of the remyelination-supportive microglia phenotype but also reinforces the notion that the primary function of microglia is the maintenance of tissue homeostasis and the support of regeneration already at the earliest stages in the development of demyelinating lesions. PMID- 22072383 TI - NARWHAL, a primary analysis pipeline for NGS data. AB - The NARWHAL software pipeline has been developed to automate the primary analysis of Illumina sequencing data. This pipeline combines a new and flexible de multiplexing tool with open-source aligners and automated quality assessment. The entire pipeline can be run using only one simple sample-sheet for diverse sequencing applications. NARWHAL creates a sample-oriented data structure and outperforms existing tools in speed. AVAILABILITY: https://trac.nbic.nl/narwhal/. PMID- 22072382 TI - Epigenetic priors for identifying active transcription factor binding sites. AB - MOTIVATION: Accurate knowledge of the genome-wide binding of transcription factors in a particular cell type or under a particular condition is necessary for understanding transcriptional regulation. Using epigenetic data such as histone modification and DNase I, accessibility data has been shown to improve motif-based in silico methods for predicting such binding, but this approach has not yet been fully explored. RESULTS: We describe a probabilistic method for combining one or more tracks of epigenetic data with a standard DNA sequence motif model to improve our ability to identify active transcription factor binding sites (TFBSs). We convert each data type into a position-specific probabilistic prior and combine these priors with a traditional probabilistic motif model to compute a log-posterior odds score. Our experiments, using histone modifications H3K4me1, H3K4me3, H3K9ac and H3K27ac, as well as DNase I sensitivity, show conclusively that the log-posterior odds score consistently outperforms a simple binary filter based on the same data. We also show that our approach performs competitively with a more complex method, CENTIPEDE, and suggest that the relative simplicity of the log-posterior odds scoring method makes it an appealing and very general method for identifying functional TFBSs on the basis of DNA and epigenetic evidence. AVAILABILITY AND IMPLEMENTATION: FIMO, part of the MEME Suite software toolkit, now supports log-posterior odds scoring using position-specific priors for motif search. A web server and source code are available at http://meme.nbcr.net. Utilities for creating priors are at http://research.imb.uq.edu.au/t.bailey/SD/Cuellar2011. CONTACT: t.bailey@uq.edu.au SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22072384 TI - Using Poisson mixed-effects model to quantify transcript-level gene expression in RNA-Seq. AB - MOTIVATION: RNA sequencing (RNA-Seq) is a powerful new technology for mapping and quantifying transcriptomes using ultra high-throughput next-generation sequencing technologies. Using deep sequencing, gene expression levels of all transcripts including novel ones can be quantified digitally. Although extremely promising, the massive amounts of data generated by RNA-Seq, substantial biases and uncertainty in short read alignment pose challenges for data analysis. In particular, large base-specific variation and between-base dependence make simple approaches, such as those that use averaging to normalize RNA-Seq data and quantify gene expressions, ineffective. RESULTS: In this study, we propose a Poisson mixed-effects (POME) model to characterize base-level read coverage within each transcript. The underlying expression level is included as a key parameter in this model. Since the proposed model is capable of incorporating base-specific variation as well as between-base dependence that affect read coverage profile throughout the transcript, it can lead to improved quantification of the true underlying expression level. AVAILABILITY AND IMPLEMENTATION: POME can be freely downloaded at http://www.stat.purdue.edu/~yuzhu/pome.html. CONTACT: yuzhu@purdue.edu; zhaohui.qin@emory.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22072385 TI - MR-Tandem: parallel X!Tandem using Hadoop MapReduce on Amazon Web Services. AB - SUMMARY: MR-Tandem adapts the popular X!Tandem peptide search engine to work with Hadoop MapReduce for reliable parallel execution of large searches. MR-Tandem runs on any Hadoop cluster but offers special support for Amazon Web Services for creating inexpensive on-demand Hadoop clusters, enabling search volumes that might not otherwise be feasible with the compute resources a researcher has at hand. MR-Tandem is designed to drop in wherever X!Tandem is already in use and requires no modification to existing X!Tandem parameter files, and only minimal modification to X!Tandem-based workflows. AVAILABILITY AND IMPLEMENTATION: MR Tandem is implemented as a lightly modified X!Tandem C++ executable and a Python script that drives Hadoop clusters including Amazon Web Services (AWS) Elastic Map Reduce (EMR), using the modified X!Tandem program as a Hadoop Streaming mapper and reducer. The modified X!Tandem C++ source code is Artistic licensed, supports pluggable scoring, and is available as part of the Sashimi project at http://sashimi.svn.sourceforge.net/viewvc/sashimi/trunk/trans_proteomic_pipeline/ xtern/xtandem/. The MR-Tandem Python script is Apache licensed and available as part of the Insilicos Cloud Army project at http://ica.svn.sourceforge.net/viewvc/ica/trunk/mr-tandem/. Full documentation and a windows installer that configures MR-Tandem, Python and all necessary packages are available at this same URL. CONTACT: brian.pratt@insilicos.com PMID- 22072386 TI - Wavelet-based image fusion in multi-view three-dimensional microscopy. AB - MOTIVATION: Multi-view microscopy techniques such as Light-Sheet Fluorescence Microscopy (LSFM) are powerful tools for 3D + time studies of live embryos in developmental biology. The sample is imaged from several points of view, acquiring a set of 3D views that are then combined or fused in order to overcome their individual limitations. Views fusion is still an open problem despite recent contributions in the field. RESULTS: We developed a wavelet-based multi view fusion method that, due to wavelet decomposition properties, is able to combine the complementary directional information from all available views into a single volume. Our method is demonstrated on LSFM acquisitions from live sea urchin and zebrafish embryos. The fusion results show improved overall contrast and details when compared with any of the acquired volumes. The proposed method does not need knowledge of the system's point spread function (PSF) and performs better than other existing PSF independent fusion methods. AVAILABILITY AND IMPLEMENTATION: The described method was implemented in Matlab (The Mathworks, Inc., USA) and a graphic user interface was developed in Java. The software, together with two sample datasets, is available at http://www.die.upm.es/im/software/SPIMFusionGUI.zip A public release, free of charge for non-commercial use, is planned after the publication of this article. PMID- 22072387 TI - Fast computation of minimum hybridization networks. AB - MOTIVATION: Hybridization events in evolution may lead to incongruent gene trees. One approach to determining possible interspecific hybridization events is to compute a hybridization network that attempts to reconcile incongruent gene trees using a minimum number of hybridization events. RESULTS: We describe how to compute a representative set of minimum hybridization networks for two given bifurcating input trees, using a parallel algorithm and provide a user-friendly implementation. A simulation study suggests that our program performs significantly better than existing software on biologically relevant data. Finally, we demonstrate the application of such methods in the context of the evolution of the Aegilops/Triticum genera. AVAILABILITY AND IMPLEMENTATION: The algorithm is implemented in the program Dendroscope 3, which is freely available from www.dendroscope.org and runs on all three major operating systems. PMID- 22072388 TI - Decompositions of large-scale biological systems based on dynamical properties. AB - MOTIVATION: Given a large-scale biological network represented as an influence graph, in this article we investigate possible decompositions of the network aimed at highlighting specific dynamical properties. RESULTS: The first decomposition we study consists in finding a maximal directed acyclic subgraph of the network, which dynamically corresponds to searching for a maximal open-loop subsystem of the given system. Another dynamical property investigated is strong monotonicity. We propose two methods to deal with this property, both aimed at decomposing the system into strongly monotone subsystems, but with different structural characteristics: one method tends to produce a single large strongly monotone component, while the other typically generates a set of smaller disjoint strongly monotone subsystems. AVAILABILITY: Original heuristics for the methods investigated are described in the article. CONTACT: altafini@sissa.it PMID- 22072390 TI - The X-linked retinitis pigmentosa protein RP2 facilitates G protein traffic. AB - The X-linked retinitis pigmentosa protein RP2 is a GTPase activating protein (GAP) for the small GTPase Arl3 and both proteins are implicated in the traffic of proteins to the primary cilia. Here, we show that RP2 can facilitate the traffic of the Gbeta subunit of transducin (Gbeta1). Glutathione S-transferase (GST)-RP2 pulled down Gbeta from retinal lysates and the interaction was specific to Gbeta1, as Gbeta3 or Gbeta5L did not bind RP2. RP2 did not appear to interact with the Gbeta:Ggamma heterodimer, in contrast Ggamma1 competed with RP2 for Gbeta binding. Overexpression of Gbeta1 in SK-N-SH cells led to a cytoplasmic accumulation of Gbeta1, while co-expression of RP2 or Ggamma1 with Gbeta1 restored membrane association of Gbeta1. Furthermore, RP2 small interfering RNA in ARPE19 cells resulted in a reduction in Gbeta1 membrane association that was rescued by Ggamma1 overexpression. The interaction of RP2 with Gbeta1 required RP2 N-terminal myristolyation and the co-factor C (TBCC) homology domain. The interaction was also disrupted by the pathogenic mutation R118H, which blocks Arl3 GAP activity. Interestingly, Arl3-Q71L competed with Gbeta1 for RP2 binding, suggesting that Arl3-GTP binding by RP2 would release Gbeta1. RP2 also stimulated the association of Gbeta1 with Rab11 vesicles. Collectively, the data support a role for RP2 in facilitating the membrane association and traffic of Gbeta1, potentially prior to the formation of the obligate Gbeta:Ggamma heterodimer. Combined with other recent evidence, this suggests that RP2 may co-operate with Arl3 and its effectors in the cilia-associated traffic of G proteins. PMID- 22072391 TI - The BH4 domain of Bcl-X(L) rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals. AB - Collective evidence indicates that motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is non-cell-autonomous and requires the interaction with the neighboring astrocytes. Recently, we reported that a subpopulation of spinal cord astrocytes degenerates in the microenvironment of motor neurons in the hSOD1(G93A) mouse model of ALS. Mechanistic studies in vitro identified a role for the excitatory amino acid glutamate in the gliodegenerative process via the activation of its inositol 1,4,5-triphosphate (IP(3))-generating metabotropic receptor 5 (mGluR5). Since non-physiological formation of IP(3) can prompt IP(3) receptor (IP(3)R)-mediated Ca(2+) release from the intracellular stores and trigger various forms of cell death, here we investigated the intracellular Ca(2+) signaling that occurs downstream of mGluR5 in hSOD1(G93A)-expressing astrocytes. Contrary to wild-type cells, stimulation of mGluR5 causes aberrant and persistent elevations of intracellular Ca(2+) concentrations ([Ca(2+)](i)) in the absence of spontaneous oscillations. The interaction of IP(3)Rs with the anti apoptotic protein Bcl-X(L) was previously described to prevent cell death by modulating intracellular Ca(2+) signals. In mutant SOD1-expressing astrocytes, we found that the sole BH4 domain of Bcl-X(L), fused to the protein transduction domain of the HIV-1 TAT protein (TAT-BH4), is sufficient to restore sustained Ca(2+) oscillations and cell death resistance. Furthermore, chronic treatment of hSOD1(G93A) mice with the TAT-BH4 peptide reduces focal degeneration of astrocytes, slightly delays the onset of the disease and improves both motor performance and animal lifespan. Our results point at TAT-BH4 as a novel glioprotective agent with a therapeutic potential for ALS. PMID- 22072392 TI - A novel tyrosine kinase inhibitor restores chondrocyte differentiation and promotes bone growth in a gain-of-function Fgfr3 mouse model. AB - Activating germline fibroblast growth factor receptor 3 (FGFR3) mutations cause achondroplasia (ACH), the most common form of human dwarfism and a spectrum of skeletal dysplasias. FGFR3 is a tyrosine kinase receptor and constitutive FGFR3 activation impairs endochondral ossification and triggers severe disorganization of the cartilage with shortening of long bones. To decipher the role of FGFR3 in endochondral ossification, we analyzed the impact of a novel tyrosine kinase inhibitor (TKI), A31, on both human and mouse mutant FGFR3-expressing cells and on the skeleton of Fgfr3(Y367C/+) dwarf mice. We found that A31 inhibited constitutive FGFR3 phosphorylation and restored the size of embryonic dwarf femurs using an ex vivo culture system. The increase in length of the treated mutant femurs was 2.6 times more than for the wild-type. Premature cell cycle exit and defective chondrocyte differentiation were observed in the Fgfr3(Y367C/+) growth plate. A31 restored normal expression of cell cycle regulators (proliferating cell nuclear antigen, KI67, cyclin D1 and p57) and allowed pre-hypertrophic chondrocytes to properly differentiate into hypertrophic chondocytes. Our data reveal a specific role for FGFR3 in the cell cycle and chondrocyte differentiation and support the development of TKIs for the treatment of FGFR3-related chondrodysplasias. PMID- 22072394 TI - Abstracts of the 2011 Advances in Inflammatory Bowel Diseases Crohn's & Colitis Foundation's National Clinical & Research Conference. December 1-3, 2011. Hollywood, Florida, USA. PMID- 22072395 TI - Platinum nanoparticle-facilitated reflective surfaces for non-contact temperature control in microfluidic devices for PCR amplification. AB - The polymerase chain reaction (PCR) is critical for amplification of target sequences of DNA or RNA that have clinical, biological or forensic relevance. While extrinsic Fabry-Perot interferometry (EFPI) has been shown to be adequate for non-contact temperature sensing, the difficulty in defining a reflective surface that is semi-reflective, non-reactive for PCR compatibility and adherent for thermal bonding has limited its exploitation. Through the incorporation of a reflective surface fabricated using a thermally driven self-assembly of a platinum nanoparticle monolayer on the surface of the microfluidic chamber, an enhanced EFPI signal results, allowing for non-contact microfluidic temperature control instrumentation that uses infrared-mediated heating, convective forced air cooling, and interferometic temperature sensing. The interferometer is originally calibrated with a miniature copper-constantan thermocouple in the PCR chamber resulting in temperature sensitivities of -22.0 to -32.8 nm. degrees C( 1), depending on the chamber depth. This universal calibration enables accurate temperature control in any device with arbitrary dimensions, thereby allowing versatility in various applications. Uniquely, this non-contact temperature control for PCR thermocycling is applied to the amplification of STR loci for human genetic profiling, where nine STR loci are successfully amplified for human identification using the EFPI-based non-contact thermocycling. PMID- 22072393 TI - Gene-gene interactions in breast cancer susceptibility. AB - There have been few definitive examples of gene-gene interactions in humans. Through mutational analyses in 7325 individuals, we report four interactions (defined as departures from a multiplicative model) between mutations in the breast cancer susceptibility genes ATM and CHEK2 with BRCA1 and BRCA2 (case-only interaction between ATM and BRCA1/BRCA2 combined, P = 5.9 * 10(-4); ATM and BRCA1, P= 0.01; ATM and BRCA2, P= 0.02; CHEK2 and BRCA1/BRCA2 combined, P = 2.1 * 10(-4); CHEK2 and BRCA1, P= 0.01; CHEK2 and BRCA2, P= 0.01). The interactions are such that the resultant risk of breast cancer is lower than the multiplicative product of the constituent risks, and plausibly reflect the functional relationships of the encoded proteins in DNA repair. These findings have important implications for models of disease predisposition and clinical translation. PMID- 22072397 TI - Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures. AB - Reduction of bone turnover with bisphosphonate treatment alters bone mineral and matrix properties. Our objective was to investigate the effect of bisphosphonate treatment on bone tissue properties near fragility fracture sites in the proximal femur in postmenopausal women with osteoporosis. The mineral and collagen properties of corticocancellous biopsies from the proximal femur were compared in bisphosphonate-naive (-BIS, n = 20) and bisphosphonate-treated (+BIS, n = 20, duration 7 +/- 5 years) patients with intertrochanteric (IT) and subtrochanteric (ST) fractures using Fourier transform infrared imaging (FTIRI). The mean values of the FTIRI parameter distributions were similar across groups, but the widths of the parameter distributions tended to be reduced in the +BIS group relative to the -BIS group. Specifically, the widths of the cortical collagen maturity and crystallinity were reduced in the +BIS group relative to those of the -BIS group by 28% (+BIS 0.45 +/- 0.18 versus -BIS 0.63 +/- 0.28, p = 0.03) and 17% (+BIS 0.087 +/- 0.012 versus -BIS 0.104 +/- 0.036, p = 0.05), respectively. When the tissue properties were examined as a function of fracture morphology within the +BIS group, the FTIR parameters were generally similar regardless of fracture morphology. However, the cortical mineral:matrix ratio was 8% greater in tissue from patients with atypical ST fractures (n = 6) than that of patients with typical (IT or spiral ST) fractures (n = 14) (Atypical 5.6 +/- 0.3 versus Typical 5.2 +/- 0.5, p = 0.03). Thus, although the mean values of the FTIR properties were similar in both groups, the tissue in bisphosphonate-treated patients had a more uniform composition than that of bisphosphonate-naive patients. The observed reductions in mineral and matrix heterogeneity may diminish tissue-level toughening mechanisms. PMID- 22072398 TI - Hydrogels in acellular and cellular strategies for intervertebral disc regeneration. AB - Low back pain is an extremely common illness syndrome that causes patient suffering and disability and requires urgent solutions to improve the quality of life of these patients. Treatment options aimed to regenerate the intervertebral disc (IVD) are still under development. The cellular complexity of IVD, and consequently its fine regulatory system, makes it a challenge to the scientific community. Biomaterials-based therapies are the most interesting solutions to date, whereby tissue engineering and regenerative medicine (TE&RM) strategies are included. By using such strategies, i.e., combining biomaterials, cells, and biomolecules, the ultimate goal of reaching a complete integration between native and neo-tissue can be achieved. Hydrogels are promising materials for restoring IVD, mainly nucleus pulposus (NP). This study presents an overview of the use of hydrogels in acellular and cellular strategies for intervertebral disc regeneration. To better understand IVD and its functioning, this study will focus on several aspects: anatomy, pathophysiology, cellular and biomolecular performance, intrinsic healing processes, and current therapies. In addition, the application of hydrogels as NP substitutes will be addressed due to their similarities to NP mechanical properties and extracellular matrix. These hydrogels can be used in cellular strategies when combined with cells from different sources, or in acellular strategies by performing the functionalization of the hydrogels with biomolecules. In addition, a brief summary of therapies based on simple injection for primary biological repair will be examined. Finally, special emphasis will focus on reviewing original studies reporting on the use of autologous cells and biomolecules such as platelet-rich plasma and their potential clinical applications. PMID- 22072399 TI - Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma. AB - PURPOSE: To determine the maximum tolerated dose and safety of the epothilone, KOS-862, in patients with advanced solid tumors or lymphoma. PATIENTS AND METHODS: Patients were treated weekly for 3 out of 4 weeks (Schedule A) or 2 out of 3 weeks (Schedule B) with KOS-862 (16-120 mg/m(2)). Pharmacokinetic (PK) sampling was performed during cycles 1 and 2; pharmacodynamic (PD) assessment for microtubule bundle formation (MTBF) was performed after the 1st dose, only at or above 100 mg/m(2). RESULTS: Thirty-two patients were enrolled, and twenty-nine completed >=1 cycle of therapy. Dose limiting toxicity [DLT] was observed at 120 mg/m(2). PK data were linear from 16 to 100 mg/m(2), with proportional increases in mean C(max) and AUC(tot) as a function of dose. Full PK analysis (mean +/- SD) at 100 mg/m(2) revealed the following: half-life (t (1/2)) = 9.1 +/- 2.2 h; volume of distribution (V(z)) = 119 +/- 41 L/m(2); clearance (CL) = 9.3 +/- 3.2 L/h/m(2). MTBF (n = 9) was seen in 40% of PBMCs within 1 h and in 15% of PBMC at 24-hours post infusion at 100 mg/m(2). Tumor shrinkage (n = 2, lymphoma), stable disease >3 months (n = 5, renal, prostate, oropharynx, cholangiocarcinoma, and Hodgkin lymphoma), and tumor marker reductions (n = 1, colorectal cancer/CEA) were observed. CONCLUSION: KOS-862 was well tolerated with manageable toxicity, favorable PK profile, and the suggestion of clinical activity. The maximum tolerated dose was determined to be 100 mg/m(2) weekly 3-on/1-off. MTBF can be demonstrated in PBMCs of patients exposed to KOS-862. PMID- 22072400 TI - Paracetamol overdose: the liver unit perspective. AB - Liver failure resulting from deliberate or accidental paracetamol overdose continues to be an important reason for referral to liver transplant centres. Severe hepatic dysfunction often appears 72-96 h after overdose. Liver injury can be prevented by timely administration of the specific antidote, N-acetylcysteine. Unfortunately, administration of N-acetylcysteine is frequently delayed due to late presentation or late administration. While N-acetylcysteine works best if given within 8 h of overdose, it is beneficial at any time period and should always be given if there is concern about significant overdose, irrespective of interval from time of ingestion. Early discussion with liver transplant unit is suggested if there is any doubt or evidence of liver failure. PMID- 22072396 TI - Inhibitory synaptic regulation of motoneurons: a new target of disease mechanisms in amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. It causes the degeneration of motoneurons and is fatal due to paralysis, particularly of respiratory muscles. ALS can be inherited, and specific disease-causing genes have been identified, but the mechanisms causing motoneuron death in ALS are not understood. No effective treatments exist for ALS. One well-studied theory of ALS pathogenesis involves faulty RNA editing and abnormal activation of specific glutamate receptors as well as failure of glutamate transport resulting in glutamate excitotoxicity; however, the excitotoxicity theory is challenged by the inability of anti-glutamate drugs to have major disease-modifying effects clinically. Nevertheless, hyperexcitability of upper and lower motoneurons is a feature of human ALS and transgenic (tg) mouse models of ALS. Motoneuron excitability is strongly modulated by synaptic inhibition mediated by presynaptic glycinergic and GABAergic innervations and postsynaptic glycine receptors (GlyR) and GABA(A) receptors; yet, the integrity of inhibitory systems regulating motoneurons has been understudied in experimental models, despite findings in human ALS suggesting that they may be affected. We have found in tg mice expressing a mutant form of human superoxide dismutase-1 (hSOD1) with a Gly93 -> Ala substitution (G93A-hSOD1), causing familial ALS, that subsets of spinal interneurons degenerate. Inhibitory glycinergic innervation of spinal motoneurons becomes deficient before motoneuron degeneration is evident in G93A-hSOD1 mice. Motoneurons in these ALS mice also have insufficient synaptic inhibition as reflected by smaller GlyR currents, smaller GlyR clusters on their plasma membrane, and lower expression of GlyR1alpha mRNA compared to wild-type motoneurons. In contrast, GABAergic innervation of ALS mouse motoneurons and GABA(A) receptor function appear normal. Abnormal synaptic inhibition resulting from dysfunction of interneurons and motoneuron GlyRs is a new direction for unveiling mechanisms of ALS pathogenesis that could be relevant to new therapies for ALS. PMID- 22072401 TI - Instrumented circumferential fusion for tuberculosis of the dorso-lumbar spine. A single or double stage procedure? AB - PURPOSE: The purpose of this study was to present our experience in treating dorso-lumbar tuberculosis by one-stage posterior circumferential fusion and to compare this group with a historical group treated by anterior debridement followed by postero-lateral fusion and stabilization. METHODS: Between 2003 and 2008, 32 patients with active spinal tuberculosis were treated by one-stage posterior circumferential fusion and prospectively followed for a minimum of two years. Pain severity was measured using Visual Analogue Scale (VAS). Neurological assessment was done using the Frankel scale. The operative data, clinical, radiological, and functional outcomes were also compared to a similar group of 25 patients treated with anterior debridement and fusion, followed 10-14 days later by posterior stabilization and postero-lateral fusion. RESULTS: The mean operative time and duration of hospital stay were significantly longer in the two stage group. The mean estimated blood loss was also larger, though insignificantly, in the two-stage group. The incidence of complications was significantly lower in the one-stage group. At final follow-up, all 34 patients with pre-operative neurological deficits showed at least one Frankel grade of neurological improvement, all 57 patients showed significant improvement of their VAS back pain score, the mean kyphotic angle has significantly improved, all patients achieved solid fusion and 43 (75.4%) patients returned to their pre disease activity level or work. CONCLUSION: Instrumented circumferential fusion, whether in one or two stages, is an effective treatment for dorso-lumbar tuberculosis. One-stage surgery, however, is advantageous because it has lower complication rate, shorter hospital stay, less operative time and blood loss. PMID- 22072402 TI - High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome. AB - Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS-related leukemias, such as GATA1 mutations in ML-DS and deregulation of the CRLF2 gene in DS-ALL. Whether microdeletions/microduplications also vary between DS and non-DS cases is presently unclear. To address this issue, we performed single nucleotide polymorphism array analyses of eight pediatric ML-DS and 17 B-cell precursor DS ALL. In the ML-DS cases, a total of 29 imbalances (20 gains and nine losses) and two partial uniparental isodisomies (pUPDs) were detected. None of the 11 small (defined as <10 Mb) imbalances were recurrent, nor were the pUPDs, whereas of the 18 large aberrations, three were recurrent-dup(1q), +8 and +21. In contrast, several frequent changes were identified in the DS-ALL cases, which harbored 82 imbalances (30 gains and 52 losses) and four pUPDs. Of the 40 large changes, 28 were gains and 12 losses, with +X, dup(Xq), dup(1q), del(7p), dup(8q), del(9p), dup(9p), del(12p), dup(17q), and +21 being recurrent. Of the 40 microdeletions identified, several targeted specific genes, with the following being repeatedly deleted: BTG1 and CDKN2A/B (29% of cases), ETV6, IKZF1, PAX5 and SERP2 (18%), and BTLA, INPP4B, P2RY8, and RB1 (12%). Loss of the SERP2 and INPP4B genes, encoding the stress-associated endoplasmic reticulum protein family member 2 and the inositol polyphosphate 4-phosphatase-II, respectively, has previously never been implicated in leukemia. Although deletions of the other genes have been associated with ALL, the high frequency of BTG1 loss is a novel finding. Such deletions may characterize a clinical subgroup of DS-ALL, comprising mainly boys with a high median age. In conclusion, ML-DS and DS-ALL are genetically distinct, with mainly gains in ML-DS and deletions in DS-ALL. Furthermore, DS-ALL is characterized by several recurrent gene deletions, with BTG1 loss being particularly frequent. PMID- 22072403 TI - Critical appraisal of the provisional DSM-5 criteria for anorexia nervosa and an alternative proposal. AB - DSM-V will be highly influential in shaping conceptions and perceptions of eating disorders by the lay public, patients, and health care providers over the next 10 15 years. DSM not only influences how medical and mental health care professionals diagnose and treat patients but also impacts health insurance policies, research funding, and clinical trials. Revisions to diagnostic criteria must be carefully considered, empirically based, and consistent with current thinking both within the field and across relevant fields. Resultant criteria should be descriptive and non-judgmental and based on empirical findings without recourse to assumed etiologies. In this forum, we review problems with the current DSM IV diagnostic criteria, concerns with the proposed DSM-5 diagnostic criteria, and present an alternative classification scheme for anorexia nervosa (AN), which more accurately captures the phenomenology of the disorder and is congruent in terminology with other fields of biomedicine. PMID- 22072404 TI - An investigation of the joint longitudinal trajectories of low body weight, binge eating, and purging in women with anorexia nervosa and bulimia nervosa. AB - OBJECTIVES: To describe the longitudinal course of three core eating disorder symptoms-low body weight, binge eating, and purging-in women with anorexia nervosa (AN) and bulimia nervosa (BN) using a novel statistical approach. METHOD: Treatment-seeking women with AN (n = 136) or BN (n = 110) completed the Eating Disorders Longitudinal Interval Follow-Up Evaluation interview every 6 months, yielding weekly eating disorder symptom data for a 5-year period. Semiparametric mixture modeling was used to identify longitudinal trajectories for the three core symptoms. RESULTS: Four individual trajectories were identified for each eating disorder symptom. The number and general shape of the individual trajectories was similar across symptoms, with each model including trajectories depicting stable absence and stable presence of symptoms as well as one or more trajectories depicting the declining presence of symptoms. Unique trajectories were found for low body weight (fluctuating presence) and purging (increasing presence). Conjunction analyses yielded the following joint trajectories: low body weight and binge eating, low body weight and purging, and binge eating and purging. DISCUSSION: The course of individual eating disorder symptoms among patients with AN and BN is highly variable. Future research identifying clinical predictors of trajectory membership may inform treatment and nosological research. PMID- 22072405 TI - Therapeutic factors affecting the cognitive behavioral treatment of bulimia nervosa via telemedicine versus face-to-face delivery. AB - OBJECTIVE: Recently, Mitchell et al. (Behav Res Ther, 46, 581-592, 2008) conducted a randomized controlled trial of an empirically supported treatment for bulimia nervosa (BN) delivered face-to-face (FTF-CBT) or via telemedicine (TV CBT). Results suggested that the TV-CBT and FTF-CBT were generally equivalent in effectiveness. The objective of the current study was to examine ratings of therapeutic alliance factors in TV-CBT and FTF-CBT. METHOD: Data obtained from 116 adults who met criteria for BN or eating disorder-not otherwise specified with binge eating or purging weekly and six doctoral-level psychologists who delivered the therapy were used in the analyses. RESULTS: Therapists generally endorsed greater differences between the treatment delivery methods than patients. Patients tended to make significantly higher ratings of therapeutic factors than therapists. DISCUSSION: TV-CBT is an acceptable method for the delivery of BN treatment compared to FTF-CBT, and TV-CBT is more easily accepted as a treatment delivery method by patients than therapists. PMID- 22072406 TI - Eating disorders in youth: diagnostic variability and predictive validity. AB - OBJECTIVE: The primary aim was to examine the utility of DSM-IV criteria in predicting treatment outcome in a sample of adolescents with eating disorders. METHOD: We (a) descriptively compared the baseline rates of anorexia nervosa (AN) and bulimia nervosa (BN) across multiple reference points for diagnostic criteria, (b) using ROC curve analyses, assessed the sensitivity and specificity of each diagnostic criterion in predicting clinical outcome, and (c) with logistic regression analyses, examined the incremental predictive value of each criterion. RESULTS: Results show a high degree of variability in the baseline diagnostic profiles as a function of the information used to inform each DSM-IV criterion. For AN, Criterion A yielded the best predictive validity, with Criteria B-D providing no significant incremental value. For BN, none of the measures had a significant AUC, and results from logistic regression analyses showed that none of the indicators were robust in predicting outcome. DISCUSSION: For AN, the existing Criterion A is appropriate for children and adolescents, and is sufficient to predict outcome in the context of active refusal to maintain a normal weight as well as multiple informants and behavioral indicators of the psychological aspects of AN. For BN, predictive validity could not be established. PMID- 22072407 TI - Consent to treatment in adolescents with anorexia nervosa. AB - OBJECTIVE: This study examined the ability of adolescents with anorexia nervosa (AN) to make treatment decisions. METHOD: The MacArthur Competence Assessment Tool-Treatment (MacCAT-T) was used to compare the decision making abilities of 35 adolescents with AN who were receiving inpatient treatment with that of 40 healthy, community-based adolescents. Vignettes of both a medical and psychiatric illness were provided, requiring participants to work through the process of making a hypothetical treatment decision. The MacCAT-T was also administered to participants with AN to examine decision-making about their own illness, which allowed for comparison of competencies across contexts. RESULTS: Group differences were found, with the community group showing superior reasoning skills to the adolescents with AN. DISCUSSION: The results provide evidence to suggest that adolescents with AN tend toward a thinking disposition that is concrete and lacking in abstract reasoning and reflection, which may negatively affect their ability to reason about treatment options. PMID- 22072408 TI - An off-line pilot evaluation of a web-based systemic cognitive-behavioral intervention for carers of people with anorexia nervosa. AB - OBJECTIVE: To evaluate the feasibility and acceptability of a novel systemic cognitive behavior therapy-based intervention for carers of people with anorexia nervosa (AN). The intervention provides information and promotes skills development in managing the illness. Carers were also offered professional support. METHOD: Twenty-seven carers were recruited. Outcomes measuring carer distress, experience of care-giving, level of expressed emotion and problem solving were measured pre- and post-intervention and at follow-up. Carers also gave feedback. RESULTS: There was a significant reduction in carers' anxiety and depression, negative experiences of caregiving and expressed emotion and a significant increase in positive experiences in caregiving after the intervention. Most improvements were maintained at follow-up. The intervention was well received. DISCUSSION: The results of this pilot study indicate that the intervention is acceptable to carers and may have a positive impact on carers' mental health and experience of care-giving. Further investigation of the intervention is warranted. PMID- 22072409 TI - Emotion contagion moderates the relationship between emotionally-negative families and abnormal eating behavior. AB - OBJECTIVE: To reconcile empirical inconsistencies in the relationship between emotionally-negative families and daughters' abnormal eating, we hypothesized a critical moderating variable: daughters' vulnerability to emotion contagion. METHOD: A nonclinical sample of undergraduate females (N = 92) was recruited via an advertisement and completed self-report measures validated for assessing: families' expressive negativity, daughters' susceptibility to emotion contagion, dietary restraint, and disinhibition, eating attitudes, and several control variables (interpersonal orientation, alexithymia, and the big five personality traits: extraversion, conscientiousness, openness, neuroticism, and agreeableness). RESULTS: All variables and interactions were entered as predictors in a multistep multiple regression equation. Only an emotion contagion by family expressivity interaction term significantly predicted unhealthy eating attitudes (beta = .29, p = .02) and dietary restraint (beta = .27, p = .03). Negatively expressive families significantly induced unhealthy eating and restraint but only among young women susceptible to emotion contagion (ps < .05). DISCUSSION: Young women susceptible to emotion contagion may be at increased risk for eating disorders. PMID- 22072410 TI - Dissatisfaction versus over-evaluation in a general population sample of women. AB - OBJECTIVE: We compared levels of eating disorder psychopathology, general psychological distress and impairment in role functioning among subgroups of women, recruited from a large, general population sample, who reported dissatisfaction with weight or shape but not over-evaluation of weight or shape (n = 482) or over-evaluation but not dissatisfaction (n = 105). METHOD: Self report questionnaires that included measures of each outcome, as well as height and weight and socio-demographic information, were completed by all participants. RESULTS: Participants who reported dissatisfaction but not over-evaluation were older, heavier and had higher levels of weight or shape concerns, higher levels of general psychological distress, and poorer physical health than those who reported over-evaluation but not dissatisfaction. However, only differences with respect to weight or shape concerns remained significant after age and BMI were statistically controlled. In multivariable analysis, dissatisfaction with weight or shape made a stronger contribution to variance in all three outcomes-eating disorder psychopathology, general psychological distress and functional impairment-than over-evaluation. DISCUSSION: Although the findings are consistent with the view that over-evaluation and dissatisfaction are distinct constructs, there was no evidence to support the premise that overevaluation is more "pathological" than dissatisfaction among women in the general population. PMID- 22072411 TI - Parental expressed emotion of adolescents with anorexia nervosa: outcome in family-based treatment. AB - OBJECTIVE: The purpose of this study was to determine the relationship between expressed emotion (EE) and outcome in family-based treatment (FBT) for anorexia nervosa (AN). METHOD: Eighty-six adolescents with AN participated in an RCT comparing two doses of FBT. Seventy-nine of these patients and their parents participated in a structured interview, from which EE ratings were made at baseline. Parents were compared on five subscales of EE as well as overall level of EE (high vs. low). RESULTS: Overall EE levels were low with 32.9% of families presenting as High EE at baseline. Ratings of baseline warmth for both mothers (p = .014) and fathers (p = .037) were related to good outcome at end-of-treatment. DISCUSSION: EE in parents of adolescents with AN is remarkably low. Notwithstanding, parental warmth may be a predictor of good outcome. PMID- 22072412 TI - Do eating attitudes predict early change in eating behaviors among women with bulimic disorders who are treated with cognitive behavioral therapy? AB - OBJECTIVE: This study examined the eating attitudes that are associated with a reduction in bulimic behaviors during the key early stage of cognitive behavioral therapy (CBT). METHOD: A case series of 41 patients with bulimia nervosa (full or partial syndrome) took part. They were drawn from the case loads of CBT therapists working in an outpatient specialist eating disorders team. Each patient completed the Eating Disorder Examination-Questionnaire and recorded the frequency of objective binges, the frequency of vomiting and the number of laxatives taken between Sessions 1 and 6. RESULTS: The participants' reduction in behaviors suggested that the early part of CBT was effective. Correlational analyses showed that those with poorer eating attitudes at the outset of therapy were likely to show the greatest behavioral change by Session 6, in keeping with findings relating to the full duration of CBT. DISCUSSION: Patients with relatively unhealthy eating attitudes are more likely to show positive behavioral change in the early part of course of CBT. Clinicians might need to encourage patients with bulimic disorders to work harder on behavioral change when the individual has less pathological eating attitudes at the outset. PMID- 22072413 TI - Tampon use in patients with anorexia nervosa can cause persistent vaginal bleeding: a case series. AB - OBJECTIVE: To describe the phenomenon of persistent vaginal bleeding in two patients with severe anorexia nervosa. METHOD: We report two cases of young women with severe anorexia nervosa reporting vaginal bleeding that persisted for months despite trials of topical and systemic conjugated estrogen therapy. RESULT: A speculum exam by a gynecologist ultimately revealed the source of the bleeding to be tampon-induced vaginal ulcers. These resolved, along with the vaginal bleeding, with vaginal estrogen cream and cessation of tampon use. DISCUSSION: Most patients with anorexia nervosa are amenorrheic due to reversion of the hypothalamic-pituitary-ovarian axis to a prepubertal state. Vaginal bleeding in patients with anorexia nervosa may trigger needless systemic hormonal treatments, radiographic studies, and multiple physician visits. A careful exam is warranted to evaluate for the presence of tampon-induced vaginal ulcer in patients with anorexia nervosa who have persistent vaginal bleeding. PMID- 22072414 TI - Metabolic and neurologic sequelae in a patient with long-standing anorexia nervosa who presented with septic shock and deep hypoglycemia. AB - OBJECTIVE: To report the case of a 48-year female with chronic remitting anorexia nervosa who was found comatose at home and admitted to our hospital with a deep hypoglycemia (glucose level 0.6 mmol/L; 11 mg/dL) and septic shock secondary to a bilateral pneumonia. METHOD: Case report. RESULTS: After admission to the critical care unit, she further displayed a number of pronounced complications known to be associated with anorexia, including hypophosphatemia, disturbed liver functions and depression of all three hematological cell lines. The neurological recovery of the patient was complicated by encephalopathy and transient tetraparesis. With initial deep hypoglycemia at presentation and persisting coma, magnetic resonance imaging performed 5 days later did not demonstrate characteristic post-hypoglycemic abnormalities. Neuroradiological examination did however reveal the presence of extensive calcifications in the basal ganglia known as Fahr's syndrome. DISCUSSION: The potential relation between anorexia nervosa and Fahr syndrome has not been described before. The fact that this patient survived a glucose level that is usually associated with a very poor outcome is probably related to its special origin. PMID- 22072415 TI - Stereoselective inhibitory effect of flurbiprofen, ibuprofen and naproxen on human organic anion transporters hOAT1 and hOAT3. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) delay the renal excretion of antifolate methotrexate by inhibiting human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8). In this study, uptake experiments were performed using Xenopus laevis oocytes to assess stereoselectivity in the inhibitory characteristics of flurbiprofen, ibuprofen and naproxen against hOAT1 and hOAT3. Uptake of p-aminohippurate by hOAT1 was inhibited by each enantiomer of the three NSAIDs, and the inhibitory effect was superior in each (S)-enantiomer around 10 uM. The apparent 50% inhibitory concentrations were estimated to be 0.615 uM for (S)-flurbiprofen, 2.84 uM for (S)-ibuprofen and 1.93 uM for (S)-naproxen, and these values were significantly lower than those of the respective (R) enantiomers [(R)-flurbiprofen: 2.35 uM, (R)-ibuprofen: 6.14 uM, (R)-naproxen: 5.26 uM]. Furthermore, the (S)-NSAIDs at 3 uM reduced methotrexate accumulation in hOAT1-expressing oocytes more strongly than the corresponding (R)-enantiomers. All enantiomers inhibited hOAT3-mediated transport of estrone sulfate and methotrexate, but there was no difference between both enantiomers of each NSAID in the inhibitory potencies. Eadie-Hofstee plot analysis showed that (S) flurbiprofen and (R)-flurbiprofen inhibited hOAT1 and hOAT3 in a competitive manner. These findings represent the stereoselective inhibitory potencies of flurbiprofen, ibuprofen and naproxen on hOAT1, and the (S)-enantiomers are greater. In contrast, stereoselectivity was not recognized in their inhibitory effect on hOAT3. PMID- 22072416 TI - Natural orifice vaginal sacrocolpopexy (NOVaS): a cadaver feasibility study. AB - INTRODUCTION AND HYPOTHESIS: The primary objective was to determine the feasibility of a vaginal approach to sacrocolpopexy using a cadaver model. Secondary objectives were to measure the distance from the vaginal introitus to the sacrum and distances of the sacral fixation elements to other vital structures. METHODS: Fourteen fresh-frozen cadavers were used. Specialized instruments were developed to optimize visualization and facilitate performance of the procedure. RESULTS: Five cadavers had a transperineal approach (an approach found unfeasible), and eight of the remaining nine had complete or partial completion of the transvaginal approach. The mean distance from the introitus to the promontory was 14.6 cm (12-16.5 cm). The mean distance from the sacral fixation elements to the aorta was 5.2 cm; common iliac artery, 3.5 cm; internal iliac artery, 3.25 cm; middle sacral artery, 1.75 cm, and ureters, 3.5 cm. The position of the sacral fixation elements was consistently at the level of S1-2. CONCLUSION: Vaginal sacrocolpopexy is feasible in a cadaver model. PMID- 22072417 TI - Quantifying vaginal tissue elasticity under normal and prolapse conditions by tactile imaging. AB - INTRODUCTION AND HYPOTHESIS: Vaginal tactile imaging (VTI) is based on principles similar to those of manual palpation. The objective of this study is to assess the clinical suitability of new approach for imaging and tissue elasticity quantification under normal and prolapse conditions. METHODS: The study subjects included 31 women with normal and prolapse conditions. The tissue elasticity (Young's modulus) was calculated from spatial gradients in the resulting 3-D tactile images. RESULTS: Average values for tissue elasticity for the anterior and posterior compartments for normal conditions were 7.4 +/- 4.3 kPa and 6.2 +/- 3.1 kPa respectively. For Stage III prolapse the average values for tissue elasticity for anterior and posterior compartments were 1.8 +/- 0.7 kPa and 1.8 +/- 0.5 kPa respectively. CONCLUSIONS: VTI may serve as a means for 3-D imaging of the vagina and a quantitative assessment of vaginal tissue elasticity, providing important information for furthering our understanding of pelvic organ prolapse and surgical treatment. PMID- 22072418 TI - Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study. AB - BACKGROUND: A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158. METHODS: The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system. The association of tumor grade with PFS and OS was assessed. RESULTS: Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2-tier system, patients with low-grade versus high-grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high-grade versus low-grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17-5.04; P = .02). CONCLUSIONS: Women with high-grade versus low-grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2-tier grading system provides a simple yet precise framework for predicting clinical outcomes. PMID- 22072420 TI - MiR-200b is involved in Tgf-beta signaling to regulate mammalian palate development. AB - Various cellular and molecular events are involved in palatogenesis, including apoptosis, epithelial-mesenchymal transition (EMT), cell proliferation, and cell migration. Smad2 and Snail, which are well-known key mediators of the transforming growth factor beta (Tgf-beta) pathway, play a crucial role in the regulation of palate development. Regulatory effects of microRNA 200b (miR-200b) on Smad2 and Snail in palatogenesis have not yet been elucidated. The aim of this study is to determine the relationship between palate development regulators miR 200b and Tgf-beta-mediated genes. Expression of miR-200b, E-cadherin, Smad2, and Snail was detected in the mesenchyme of the mouse palate, while miR-200b was expressed in the medial edge epithelium (MEE) and palatal mesenchyme. After the contact of palatal shelves, miR-200b was no longer expressed in the mesenchyme around the fusion region. The binding activity of miR-200b to both Smad2 and Snail was examined using a luciferase assay. MiR-200b directly targeted Smad2 and Snail at both cellular and molecular levels. The function of miR-200b was determined by overexpression via a lentiviral vector in the palatal shelves. Ectopic expression of miR-200b resulted in suppression of these Tgf-beta-mediated regulators and changes of apoptosis and cell proliferation in the palatal fusion region. These results suggest that miR-200b plays a crucial role in regulating the Smad2, Snail, and in apoptosis during palatogenesis by acting as a direct non coding, influencing factor. Furthermore, the molecular interactions between miR 200b and Tgf-beta signaling are important for proper palatogenesis and especially for palate fusion. Elucidating the mechanism of palatogenesis may aid the design of effective gene-based therapies for the treatment of congenital cleft palate. PMID- 22072419 TI - Keratocystic odontogenic tumour (KCOT)--a cyst to a tumour. AB - PURPOSE: The World Health Organization (WHO) has reclassified 'odontogenic keratocyst' (OKC) to 'keratocystic odontogenic tumour' (KCOT) in 2005. Currently, this tumour is classified as a benign neoplasm of odontogenic origin and not as a cyst. This article reviews and discusses history, classification scheme, aetiology and pathogenesis, molecular and genetic basis, incidence, epidemiology and site, clinical features, imaging, histopathology, immunohistochemistry, treatment options, prognosis, recurrence and malignant transformation of KCOT, with emphasis on understanding the basis of reclassification as 'keratocystic odontogenic tumour'. METHODS: A systematic search and review of the literature was carried out in the online database of the United States National Library of Medicine to identify eligible titles for the study. RESULTS: Current evidence suggests that the scientific community still continues to use the term 'odontogenic keratocyst' more favourably than 'keratocystic odontogenic tumour'. CONCLUSION: The online database search indicates that the scientific community still continues to use the term 'odontogenic keratocyst' more favourably than 'keratocystic odontogenic tumour'. At this juncture, where the terminology has changed from a cyst to a tumour, a thorough review of literature on KCOT is presented. PMID- 22072421 TI - Role of CD44 in the organization of keratinocyte pericellular hyaluronan. AB - CD44 is a ubiquitous cell surface glycoprotein, involved in important cellular functions including cell adhesion, migration, and modulation of signals from cell surface receptors. While most of these CD44 functions are supposed to involve hyaluronan, relatively little is known about the contribution of CD44 to hyaluronan maintenance and organization on cell surface, and the role of CD44 in hyaluronan synthesis and catabolism. Blocking hyaluronan binding either by CD44 antibodies, CD44-siRNA or hyaluronan decasaccharides (but not hexasaccharides) removed most of the hyaluronan from the surfaces of both human (HaCaT) and mouse keratinocytes, resembling results on cells from CD44-/- animals. In vitro, compromising CD44 function led to reduced and increased amounts, respectively, of intracellular and culture medium hyaluronan, and specific accumulation below the cells. In vivo, CD44-deficiency caused no marked differences in hyaluronan staining intensity or localization in the fetal skin or in adult ear skin, while tail epidermis showed a slight reduction in epidermal hyaluronan staining intensity. However, CD44-deficient tail skin challenged with retinoic acid or tape stripping revealed diffuse accumulation of hyaluronan in the superficial epidermal layers, normally negative for hyaluronan. Our data indicate that CD44 retains hyaluronan in the keratinocyte pericellular matrix, a fact that has not been shown unambiguously before, and that hyaluronan abundance in the absence of CD44 can result in hyaluronan trapping in abnormal locations possibly interfering there with normal differentiation and epidermal barrier function. PMID- 22072424 TI - Two-temperature hybridization for microarray detection of label-free microRNAs with attomole detection and superior specificity. AB - Two is better than one: Two short locked nucleic acid based probes were used to collectively capture and detect microRNAs by a simple two-temperature hybridization process. Intact microRNAs were directly measured down to attomolar concentrations with a high specificity and nearly four orders of magnitude of dynamic range. Single base mismatches in the microRNAs were potently discriminated from the perfectly matched targets. PMID- 22072423 TI - Regulation of proton-coupled folate transporter in retinal Muller cells by the antipsoriatic drug monomethylfumarate. AB - Fumaric acid esters are used to treat psoriasis, an inflammatory skin disease characterized by keratinocyte proliferation. Inflammation and proliferation are hallmarks of retinal disease; hence, fumaric acid esters may have therapeutic value in retinal pathology. In diseased retinas, Muller glial cells (MCs) undergo reactive gliosis, a hyperproliferative state. MCs take up folate, a vitamin necessary for cell proliferation, via the proton-coupled folate transporter (PCFT). Here we examined the effect of monomethylfumarate (MMF), the active metabolite of fumaric acid esters, on expression and function of PCFT in MCs. Primary MCs, isolated from neonatal mouse retinas, were treated with MMF, and PCFT function was monitored by measuring uptake of radiolabeled methyltetrahydrofolate (MTF) at pH 5.5. Dose-response and time-course analyses were performed to identify optimal conditions for maximal effect. The influence of MMF treatment on kinetic parameters of PCFT was studied, and PCFT expression was analyzed at the mRNA and protein level. MTF uptake in MCs decreased by ~50% following 18 h treatment with 1 mM MMF. This effect was specific to fumaric acid esters. MMF treatment decreased the maximal velocity of the transporter without altering substrate affinity. The decrease in PCFT function following MMF treatment was accompanied by attenuated PCFT expression. This is the first report that an antipsoriatic compound can regulate folate transport in MCs and may have potential for the treatment of reactive gliosis in retinal disease. PMID- 22072426 TI - Quantitative multispectral imaging of Herovici's polychrome for the assessment of collagen content and tissue remodelling. AB - Bioprosthetic devices, constructed from a variety of materials, are routinely implanted in a variety of anatomical locations. Essential to their success is the formation of a non-destructive interface with the host tissue and appropriate tissue remodelling. Traditionally, the main method of assessing the host-material interface has been qualitative histological evaluation, using pattern recognition and comparative assessment to identify changes in the normal tissue architecture that are characteristic of scar tissue. In the present study, the recently developed technique of multispectral imaging was used to revisit a little described histological stain, Herovici's polychrome, which is capable of distinguishing between types I and III collagen. Combined, these techniques allowed quantification of collagen content and distribution of collagen types within a tissue sample. Samples of rat tail and human scar tissue were used to optimize the staining, while comparison with immunolabelled samples was used to develop a reproducible quantification system, based on the specific colour profiles for types I and III collagen. Finally the remodelling of rat abdominal wall defects repaired with crosslinked or non-crosslinked extracellular matrix scaffolds derived from porcine urinary bladder was assessed with this technique. Compared to standard histological assessment, the combination of multispectral imaging and Herovici's polychrome staining presents a quick, simple, reliable technique that can provide accurate quantification of tissue remodelling and specifically identify the expression and distribution of types I and III collagen. PMID- 22072425 TI - Interactions between extracellular signal-regulated kinase 1/2 and p38 MAP kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity. AB - RUNX2, a key transcription factor for osteoblast differentiation, is regulated by ERK1/2 and p38 MAP kinase-mediated phosphorylation. However, the specific contribution of each kinase to RUNX2-dependent transcription is not known. Here we investigate ERK and p38 regulation of RUNX2 using a unique P-RUNX2-specific antibody. Both MAP kinases stimulated RUNX2 Ser319 phosphorylation and transcriptional activity. However, a clear preference for ERK1 versus p38alpha/beta was found when the ability of these MAPKs to phosphorylate and activate RUNX2 was compared. Similarly, ERK1 preferentially bound to a consensus MAPK binding site on RUNX2 that was essential for the activity of either kinase. To assess the relative contribution of ERK1/2 and p38 to osteoblast gene expression, MC3T3-E1 preosteoblast cells were grown in control or ascorbic acid (AA)-containing medium +/- BMP2/7. AA-induced gene expression, which requires collagen matrix synthesis, was associated with parallel increases in P-ERK and RUNX2-S319-P in the absence of any changes in P-p38. This response was blocked by ERK, but not p38, inhibition. Significantly, in the presence of AA, BMP2/7 synergistically stimulated RUNX2 S319 phosphorylation and transcriptional activity without affecting total RUNX2 and this response was totally dependent on ERK/MAPK activity. In contrast, although p38 inhibition partially blocked BMP dependent transcription, it did not affect RUNX2 S319 phosphorylation, suggesting the involvement of other phosphorylation sites and/or transcription factors in this response. Based on this work, we conclude that extracellular matrix and BMP regulation of RUNX2 phosphorylation and transcriptional activity in osteoblasts is predominantly mediated by ERK rather than p38 MAPKs. PMID- 22072427 TI - Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy. AB - To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE). We analyzed the presence of mild cognitive impairment (CI) by using the PHES battery of psychometric tests and measured the levels of ammonia and of the inflammatory cytokines IL-6 and IL-18 in blood of patients with different types of liver or dermatological diseases resulting in different grades of hyperammonemia and/or inflammation. The study included patients with 1) liver cirrhosis, showing hyperammonemia and inflammation; 2) non alcoholic fatty liver disease (NAFLD) showing inflammation but not hyperammonemia; 3) non-alcoholic steatohepatitis (NASH) showing inflammation and very mild hyperammonemia; 4) psoriasis, showing inflammation but not hyperammonemia; 5) keloids, showing both inflammation and hyperammonemia and 6) controls without inflammation or hyperammonemia. The data reported show that in patients with liver diseases, cognitive impairment may appear before progression to cirrhosis if hyperammonemia and inflammation are high enough. Five out of 11 patients with NASH, without liver cirrhosis, showed cognitive impairment associated with hyperammonemia and inflammation. Patients with keloids showed cognitive impairment associated with hyperammonemia and inflammation, in the absence of liver disease. Hyperammonemia or inflammation alone did not induce CI but the combination of certain levels of hyperammonemia and inflammation is enough to induce CI, even without liver disease. PMID- 22072428 TI - Evaluating the ameliorative effect of natural dissolved organic matter (DOM) quality on copper toxicity to Daphnia magna: improving the BLM. AB - Various quality predictors of seven different natural dissolved organic matter (DOM) and humic substances were evaluated for their influence on protection of Daphnia magna neonates against copper (Cu) toxicity. Protection was examined at 3 and 6 mg l(-1) of dissolved organic carbon (DOC) of each DOM isolate added to moderately hard, dechlorinated water. Other water chemistry parameters (pH, concentrations of DOC, calcium, magnesium and sodium) were kept relatively constant. Predictors included absorbance ratios Abs(254/365) (index of molecular weight) and Abs-octanol(254)/Abs-water(254) (index of lipophilicity), specific absorption coefficient (SAC(340); index of aromaticity), and fluorescence index (FI; index of source). In addition, the fluorescent components (humic-like, fulvic-like, tryptophan-like, and tyrosine-like) of the isolates were quantified by parallel factor analysis (PARAFAC). Up to 4-fold source-dependent differences in protection were observed amongst the different DOMs. Significant correlations in toxicity amelioration were found with Abs(254/365), Abs-octanol(254)/Abs water(254), SAC(340), and with the humic-like fluorescent component. The relationships with FI were not significant and there were no relationships with the tryptophan-like or tyrosine-like fluorescent components at 3 mg C l(-1), whereas a negative correlation was seen with the fulvic-like component. In general, the results indicate that larger, optically dark, more lipophilic, more aromatic DOMs of terrigenous origin, with higher humic-like content, are more protective against Cu toxicity. A method for incorporating SAC(340) as a DOM quality indicator into the Biotic Ligand Model is presented; this may increase the accuracy for predicting Cu toxicity in natural waters. PMID- 22072429 TI - Lack of association of cadherin expression and histopathologic type, metastasis, or patient outcome in oropharyngeal squamous cell carcinoma: a tissue microarray study. AB - Altered cadherin expression is important for metastasis in many carcinomas including head and neck squamous cell carcinoma (SCC). We evaluated E- and N cadherin expression specifically in oropharyngeal SCC and correlated this with clinical and pathologic features. Oropharyngeal SCC patients with clinical follow up information were identified from clinician databases from 1996 through 2007 and tissue microarrays created. Tumors had been previously typed histopathologically as keratinizing, non-keratinizing, or non-keratinizing with maturation, and had known p16 and human papillomavirus status, respectively. Immunohistochemistry was performed on the microarrays, and staining was evaluated for presence and intensity (0 = negative, 1 = weak, 2 = moderate, 3 = strong) both visually and also with digital image analysis software. Of 154 cases, E cadherin was expressed in 152 (98.7%) and N-cadherin in 17 (11.5%). Neither E- nor N-cadherin expression was statistically significantly associated with histopathologic type (P = 0.082 and P = 0.228, respectively). E-cadherin staining intensity was not statistically significantly associated with nodal or distant metastasis, either visually or by image analysis, (P = 0.098 and P = 0.963 respectively) nor was N-cadherin (P = 0.228 and P = 0.935 respectively). Neither E- nor N-cadherin expression was associated with death from disease (P = 0.995; P = 0.964, respectively). E-cadherin is extensively expressed by oropharyngeal SCC, even the non-keratinizing type. Our results suggest that cadherin expression may not be a predictor for nodal or distant metastasis in these tumors. Mechanisms independent of cadherin expression may be important for metastases in oropharyngeal SCC. PMID- 22072431 TI - Bridging the gap with an ileocolonic graft after extensive colorectal resections. AB - BACKGROUND: Ileocecal interposition (ICI) for first-line reconstruction after low anterior colorectal resection was introduced by von Flue and Harder in 1994 (Dis Colon Rectum 37:1160-1162, 1994). We report our experience using this technique to bridge colonic gaps after significant loss of bowel length. PATIENTS AND METHODS: Between 1999 and 2009 the left-sided colon was too short for traditional isoperistaltic reconstruction in six patients treated in our hospital. Reasons for extensive bowel loss were a deficient (n = 3) or torn (n = 1) marginal artery with ischemia or repeat colorectal resections (n = 2). An ICI was done to bridge the gap and enable restoration of intestinal continuity. RESULTS: No patient died. Whenever performing a coloanal anastomosis (4/6) a loop ileostomy was raised. One patient with colonic diversion experienced graft-related complications: ischemic colitis of the interposed colonic segment, anastomotic stenosis, and a presacral sinus were observed and managed nonoperatively. Subsequent closure of the stoma was possible in all cases. A median Vaizey incontinence score of 9 (range: 4-14) was recorded in the patient with coloanal anastomosis. The average number of bowel movements per day was 1.5 (range: 0.5 6). CONCLUSIONS: When the descending colon does not reach the rectal stump or anal canal in reoperative cases or after vascular complication, ICI is a useful salvage procedure resulting in good bowel function. PMID- 22072430 TI - Ghrelin agonist TZP-101/ulimorelin accelerates gastrointestinal recovery independently of opioid use and surgery type: covariate analysis of phase 2 data. AB - BACKGROUND: Delayed recovery of gastrointestinal (GI) motility is a common complication following surgery. TZP-101/ulimorelin is a macrocyclic peptidomimetic ghrelin receptor agonist with GI promotility effects that significantly accelerates time to recovery of GI motility compared to placebo following partial colectomy. It is also well tolerated. The objectives of this analysis were to identify predictors of GI motility recovery in patients undergoing partial colectomy and to evaluate whether these factors affect ulimorelin acceleration of GI recovery. METHODS: Covariate analysis assessed the effect of eight variables-age, sex, body mass index, type of surgery (right colectomy, left colectomy, other), duration of surgery, blood loss, total opioid consumption, country-on recovery of GI motility in 236 patients randomized to ulimorelin (n = 168) or placebo (n = 68). The primary endpoint was the recovery of GI function (time from the end of surgery to first bowel movement). Stepwise regression identified a parsimonious model of the smallest subset of variables best predicting GI recovery. RESULTS: Recovery was shorter for segmental/subtotal colectomies vs. right colectomies (P = 0.016) and longer with increased total opioid use (P = 0.037). The remaining variables had no statistically significant effect on GI recovery. Effects of ulimorelin 480 MUg/kg (the most effective dose) on time to GI tract recovery remained statistically and clinically significant (hazard ratio = 1.81, P = 0.014) when adjusted for surgery type and/or total opioid use. CONCLUSIONS: Two factors, type of surgery and total opioid use, independently modified times to recovery of GI motility following partial large bowel resection surgery. Acceleration of recovery of GI motility by ulimorelin was independent of these factors. PMID- 22072432 TI - Identification of novel GH-regulated genes in C2C12 cells. AB - Growth hormone (GH) is the main regulator of longitudinal growth before puberty, and treatment with human recombinant (rh) GH can increase muscle strength. Nevertheless, molecular mechanisms responsible remain mostly unknown. Many physiological effects of GH require hormone-mediated changes in gene expression. In an attempt to gain insight into the mechanism of GH action in muscle cells we evaluated the effects of rhGH on gene expression profile in a murine skeletal muscle cell line C2C12. The objective of the work was to identify changes in gene expression in the murine skeletal muscle cell line C2C12 after rGH treatment using microarray assays. C2C12 murine skeletal muscle cell cultures were differentiated during 4 days. After 16 h growing in serum-free medium, C2C12 myotubes were stimulated during 6 h with 500 ng/ml rhGH. Four independent sets of experiments were performed to identify GH-regulated genes. Total RNA was isolated and subjected to analysis. To validate changes candidate genes were analyzed by real-time quantitative polymerase chain reaction. One hundred and fifty-four differentially expressed genes were identified; 90 upregulated and 64 downregulated. Many had not been previously identified as GH-responsive. Real time PCR in biological replicates confirmed the effect of rGH on 15 genes: Cish, Serpina3g, Socs2, Bmp4, Tnfrsf11b, Rgs2, Tgfbr3, Ugdh, Npy1r, Gbp6, Tgfbi, Tgtp, Btc, Clec3b, and Bcl6. This study shows modifications in the gene expression profile of the C2C12 cell line after rhGH exposure. In vitro and gene function analysis revealed genes involved in skeletal and muscle system as well as cardiovascular system development and function. PMID- 22072433 TI - A weekly administered sustained-release growth hormone reduces visceral fat and waist circumference in abdominal obesity. AB - Administration of recombinant human growth hormone (rhGH) in obesity has been known to lead to a decrease in visceral adiposity and an increase in lean body mass. Most studies have used supraphysiological doses of rhGH, which were administered daily or every other day. We aimed to evaluate whether weekly administered low dose of sustained-release rhGH (SR-rhGH) could play a therapeutic role in the treatment of abdominal obesity. Prospective, single-arm, open-label, multicenter pilot study was carried out. Participants were 26 adults aged 40-65 years old with abdominal obesity (male: waist circumference >90 cm, female: waist circumference >85 cm). The subjects were given 3 mg of SR-rhGH, administered subcutaneously, weekly for 26 weeks. SR-rhGH treatment for 26 weeks increased the IGF-1 level by 56.53+/-76.09 MUg/l (SDS 0.77+/-1.12) compared to the baseline (p=0.0022). After 26 weeks, SR-rhGH treatment reduced abdominal visceral adipose tissue (VAT) (140.35+/-75.97 to 128.43+/-73.85 cm2, p=0.0038). Average waist circumference decreased from 96.25+/-6.41 to 91.93+/-6.13 cm (p<0.0001) after treatment. However, body weight or lean body mass did not show any significant change. In conclusion, SR-rhGH treatment for 26 weeks reduced abdominal visceral fat and waist circumference without severe adverse events. Further studies may be considered on the role of weekly administered SR-rhGH as a treatment for abdominal obesity. PMID- 22072434 TI - Sequential microfluidic droplet processing for rapid DNA extraction. AB - This work describes a novel droplet-based microfluidic device, which enables sequential droplet processing for rapid DNA extraction. The microdevice consists of a droplet generation unit, two reagent addition units and three droplet splitting units. The loading/washing/elution steps required for DNA extraction were carried out by sequential microfluidic droplet processing. The movement of superparamagnetic beads, which were used as extraction supports, was controlled with magnetic field. The microdevice could generate about 100 droplets per min, and it took about 1 min for each droplet to perform the whole extraction process. The extraction efficiency was measured to be 46% for lambda-DNA, and the extracted DNA could be used in subsequent genetic analysis such as PCR, demonstrating the potential of the device for fast DNA extraction. PMID- 22072435 TI - Production of multiple extracellular enzyme activities by novel submerged culture of Aspergillus kawachii for ethanol production from raw cassava flour. AB - Cassava is a starch-containing root crop that is widely used as a raw material in a variety of industrial applications, most recently in the production of fuel ethanol. In the present study, ethanol production from raw (uncooked) cassava flour by simultaneous saccharification and fermentation (SSF) using a preparation consisting of multiple enzyme activities from Aspergillus kawachii FS005 was investigated. The multi-activity preparation was obtained from a novel submerged fermentation broth of A. kawachii FS005 grown on unmilled crude barley as a carbon source. The preparation was found to consist of glucoamylase, acid-stable alpha-amylase, acid carboxypeptidase, acid protease, cellulase and xylanase activities, and exhibited glucose and free amino nitrogen (FAN) production rates of 37.7 and 118.7 mg/l/h, respectively, during A. kawachii FS005-mediated saccharification of uncooked raw cassava flour. Ethanol production from 18.2% (w/v) dry uncooked solids of raw cassava flour by SSF with the multi-activity enzyme preparation yielded 9.0% (v/v) of ethanol and 92.3% fermentation efficiency. A feasibility study for ethanol production by SSF with a two-step mash using raw cassava flour and the multi-activity enzyme preparation manufactured on-site was verified on a pilot plant scale. The enzyme preparation obtained from the A. kawachii FS005 culture broth exhibited glucose and FAN production rates of 41.1 and 135.5 mg/l/h, respectively. SSF performed in a mash volume of about 1,612 l containing 20.6% (w/v) dry raw cassava solids and 106 l of on-site manufactured A. kawachii FS005 culture broth yielded 10.3% (v/v) ethanol and a fermentation efficiency of 92.7%. PMID- 22072436 TI - Characterization of alginate lyase gene using a metagenomic library constructed from the gut microflora of abalone. AB - A metagenomic fosmid library was constructed using a genomic DNA mixture extracted from the gut microflora of abalone. The library gave an alginate lyase positive clone (AlyDW) harboring a 31.7-kbp insert. The AlyDW insert consisted of 22 open reading frames (ORFs). The deduced amino acid sequences of ORFs 11-13 were similar to those of known alginate lyase genes, which are found adjacent in the genome of Klebsiella pneumoniae subsp. aerogenes, Vibrio splendidus, and Vibrio sp. belonging to the phylum Gammaproteobacteria. Among the three recombinant proteins expressed from the three ORFs, alginate lyase activity was only observed in the recombinant protein (AlyDW11) coded by ORF 11. The expressed protein (AlyDW11) had the highest alginate lyase activity at pH 7.0 and 45 degrees C in the presence of 1 mM AgNO(3). The alginate lyase activity of ORF 11 was confirmed to be endolytic by thin-layer chromatography. AlyDW11 preferred poly(beta-D: -mannuronate) as a substrate over poly(alpha-L: -guluronate). AlyDW11 contained three highly conserved regions, RSEL, QIH, and YFKAGVYNQ, which may act to stabilize the three-dimensional conformation and function of the alginate lyase. PMID- 22072437 TI - Alginate production and alg8 gene expression by Azotobacter vinelandii in continuous cultures. AB - Alginates are polysaccharides that are used as thickening agents, stabilizers, and emulsifiers in various industries. These biopolymers are produced by fermentation with a limited understanding of the processes occurring at the cellular level. The objective of this study was to evaluate the effects of agitation rate and inlet sucrose concentrations (ISC) on alginate production and the expression of the genes encoding for alginate-lyases (algL) and the catalytic subunit of the alginate polymerase complex (alg8) in chemostat cultures of Azotobacter vinelandii ATCC 9046. Increased alginate production (2.4 g l-1) and a higher specific alginate production rate (0.1 g g-1 h-1) were obtained at an ISC of 15 g l-1. Carbon recovery of about 100% was obtained at an ISC of 10 g l-1, whereas it was close to 50% at higher ISCs, suggesting that cells growing at lower sucrose feed rates utilize the carbon source more efficiently. In each of the steady states evaluated, an increase in algL gene expression was not related to a decrease in alginate molecular weight, whereas an increase in the molecular weight of alginate was linked to higher alg8 gene expression, demonstrating a relationship between the alg8 gene and alginate polymerization in A. vinelandii for the first time. The results obtained provide a possible explanation for changes observed in the molecular weight of alginate synthesized and this knowledge can be used to build a recombinant strain able to overexpress alg8 in order to produce alginates with higher molecular weights. PMID- 22072438 TI - Prognostic implications of genetic aberrations in acute myelogenous leukemia with normal cytogenetics. AB - Acute myelogenous leukemia (AML) is a genetically heterogeneous disease in which somatic mutations, that disturb cellular growth, proliferation, and differentiation, accumulate in hematopoietic progenitor cells. Cytogenetic findings, at diagnosis, have been proven to be one of the most important prognostic indicators in AML. About half of the patients with AML are found to have "normal" cytogenetic analysis by standard culture techniques. These patients are considered as an intermediate risk group. Cytogenetically normal AML (CN-AML) is the largest cytogenetic risk group, and the variation in clinical outcome of patients in this group is greater than in any other cytogenetic group. Besides mutation testing, age and presenting white blood cell count are important predictors of overall survival, suggesting that other factors independent of cytogenetic abnormalities, contribute to the outcome of patients with AML. The expanding knowledge at the genetic and molecular levels is helping define several subgroups of patients with CN-AML with variable prognosis. In this review, we describe the clinical and prognostic characteristics of CN-AML patients as a group, as well as the various molecular and genetic aberrations detected in these patients and their clinical and prognostic implications. PMID- 22072440 TI - Instrumental variables in epidemiological research: an assessment of the adoption rate and future trends. PMID- 22072439 TI - High prevalence of CIC fusion with double-homeobox (DUX4) transcription factors in EWSR1-negative undifferentiated small blue round cell sarcomas. AB - Primitive round cell sarcomas of childhood and young adults have been problematic to diagnose and classify. Our goal was to investigate the pathologic and molecular characteristics of small blue round cell tumors (SBRCT) that remained unclassified after exhaustive immunohistochemistry and molecular screening to exclude known sarcoma-related translocations. As rare examples of EWSR1-negative SBRCT have been shown to carry rearrangements for FUS and CIC genes, we undertook a systematic screening for these two genes. CIC rearrangements by FISH were detected in 15/22 (68%), while none showed FUS abnormalities. RACE, RT-PCR, and/or long-range DNA PCR performed in two cases with frozen material showed that CIC was fused to copies of the DUX4 gene on either 4q35 or 10q26.3. Subsequent FISH analysis confirmed fused signals of CIC with either 4q35 or 10q26.3 region in six cases each. Tumors positive for CIC-DUX4 fusion occurred mainly in male young adult patients (median age: 29 years), with the extremities being the most frequent location. Microscopically, tumors displayed a primitive, round to oval cell morphology with prominent nucleoli, high mitotic count, and areas of necrosis. O13 expression was variable, being either diffuse or patchy and tumors mostly lacked other markers of differentiation. Although CIC-DUX4 resulting in a t(4;19) translocation has been previously described in primitive sarcomas, this is the first report implicating the related DUX4 on 10q26 in oncogenesis. These results suggest the possibility of a newly defined subgroup of primitive round cell sarcomas characterized by CIC rearrangements, distinct from Ewing sarcoma family of tumors. PMID- 22072442 TI - Cardiovascular responses to water ingestion at rest and during isometric handgrip exercise. AB - Water drinking activates sympathetic vasoconstriction in healthy young adults; however, this is not accompanied by a concomitant increase in resting blood pressure. It is not known whether the water pressor effect is unmasked by a physiological condition such as exercise. Therefore, we examined the effect of water ingestion (50 vs. 500 mL) on the cardiovascular and autonomic responses to isometric handgrip in 17 healthy participants (9 men, 8 women, aged 28.4 +/- 9.7 years). Beat-to-beat blood pressure and R-R intervals were recorded in both conditions at rest (pre- and post-ingestion) and during handgrip at 30% of maximal voluntary contraction. R-R series were spectrally decomposed using an autoregressive approach. Water ingestion did not interact with the increase in mean arterial pressure (MAP) from rest to exercise, which was similar between conditions. In contrast, there was an overall bradycardic effect of water and this was accompanied by increased high frequency power (condition main effect, p < 0.05). When the differences in high frequency power between conditions were controlled for, MAP was significantly higher after drinking 500 mL of water (condition main effect, p < 0.05). In addition, water ingestion attenuated the increase in the low to high frequency power ratio from rest to handgrip (interaction effect, p < 0.05). In conclusion, the rise in blood pressure post water ingestion is prevented both at rest and during isometric handgrip. Interestingly, this is not sustained after controlling for the enhanced vagal drive caused by water ingestion. Therefore, the mechanisms underlying this response most likely depend on reflex bradycardia of vagal origin. PMID- 22072443 TI - Increased p75 neurotrophin receptor expression in the canine distemper virus model of multiple sclerosis identifies aldynoglial Schwann cells that emerge in response to axonal damage. AB - Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide regeneration-promoting cells recruitable for therapeutic purposes. There is accumulating evidence that aldynoglial cells with Schwann cell-like growth-promoting properties emerge in the lesioned CNS. However, the characterization of these cells and the signals triggering their in situ generation have remained enigmatic. In the present study, we used the p75 neurotrophin receptor (p75(NTR) ) as a marker for Schwann cells to study gliogenesis in the well-defined canine distemper virus (CDV)-induced demyelination model. White matter lesions of CDV-infected dogs contained bi- to multipolar, p75(NTR) -expressing cells that neither expressed MBP, GFAP, BS-1, or P0 identifying oligodendroglia, astrocytes, microglia, and myelinating Schwann cells nor CDV antigen. Interestingly, p75(NTR) -expression became apparent prior to the onset of demyelination in parallel to the expression of beta-amyloid precursor protein (beta-APP), nonphosphorylated neurofilament (n-NF), BS-1, and CD3, and peaked in subacute lesions with inflammation. To study the role of infiltrating immune cells during differentiation of Schwann cell-like glia, organotypic slice cultures from the normal olfactory bulb were established. Despite the absence of infiltrating lymphocytes and macrophages, a massive appearance of p75(NTR) -positive Schwann-like cells and BS-1-positive microglia was noticed at 10 days in vitro. It is concluded that axonal damage as an early signal triggers the differentiation of tissue-resident precursor cells into p75(NTR) -expressing aldynoglial Schwann cells that retain an immature pre-myelin state. Further studies have to address the role of microglia during this process and the regenerative potential of aldynoglial cells in CDV infection and other demyelinating diseases. PMID- 22072441 TI - Racial disparities in receipt and comparative effectiveness of oxaliplatin for stage III colon cancer in older adults. AB - BACKGROUND: African Americans in the United States have higher rates of colon cancer mortality than other races. This study examines the use of oxaliplatin, a novel chemotherapeutic agent approved in 2004, among African American and Caucasian American patients with stage III colon cancer to determine whether differential receipt or differential effectiveness of the drug may explain the racial disparity in colon cancer mortality. METHODS: The authors conducted a population-based retrospective cohort study of stage III colon cancer patients aged 65 years and older treated from 2004 through 2006 who initiated chemotherapy within 90 days of surgical resection (N = 1162) using Surveillance, Epidemiology and End Results-Medicare data. Patients receiving oxaliplatin (n = 477) were compared with those receiving 5-fluorouracil without oxaliplatin (n = 685). The authors estimated prevalence ratios and hazard ratios (HRs) using multivariate binomial regression and Cox models to evaluate racial differences in oxaliplatin receipt and survival. RESULTS: African Americans were as likely as Caucasian Americans to receive oxaliplatin (40.5 vs 41.1%; prevalence ratio, 0.90; 95% confidence interval [CI], 0.71-1.13). Oxaliplatin was associated with lower mortality compared with 5-fluorouracil (HR, 0.76; 95% CI, 0.58-1.00). This benefit appeared stronger among African Americans (HR, 0.31; 95% CI, 0.09-1.05) than Caucasian Americans (HR, 0.80; 95% CI, 0.60-1.06). CONCLUSIONS: In Medicare insured patients receiving chemotherapy, the authors observed no meaningful racial disparities in receipt of oxaliplatin and, among those receiving it, potentially better survival among African Americans. Differential receipt and effectiveness of oxaliplatin-containing regimens does not appear to contribute to the previously documented racial disparities in colon cancer survival. Understanding reasons for potentially enhanced effectiveness among African Americans may inform efforts to resolve racial disparities in colon cancer outcomes. PMID- 22072444 TI - Molecular engineering of zinc phthalocyanines with phosphinic acid anchoring groups. PMID- 22072445 TI - Assessment of the interactive effects of ambient O3 and NPK levels on two tropical mustard varieties (Brassica campestris L.) using open-top chambers. AB - Rising O(3) concentrations in agricultural areas have been identified as a significant threat to crop production in Asia including India. The present work reports the results of a field study conducted to assess the usefulness of higher than recommended NPK dose in modifying the physiological, growth, yield, and seed quality responses of two mustard (Brassica campestris L. var. Vardan and Aashirwad) varieties under ambient ozone level at a rural site of India, using open-top chambers. Twelve hourly mean O(3) concentrations ranged between 27.7 and 59.04 ppb during the growth period. Plants in nonfiltered chambers (NFCs) showed reductions in photosynthetic rate, stomatal conductance, and growth parameters compared to the plants in filtered chambers (FCs), but reductions were of lower magnitude at 1.5 times recommended dose of NPK (1.5 RNPK) compared to recommended (RNPK). Yield and seed quality reduced significantly in plants of NFCs compared to FCs at RNPK, but no significant differences were recorded at 1.5 RNPK. There were higher N uptake and N uptake efficiency of plants in FCs compared to NFCs. Nitrogen utilization efficiency increased in Vardan, but decreased in Aashirwad in NFCs compared to FCs suggesting higher capability of N acquisition and utilization under ambient O(3), which led to a less pronounced reduction in the yield of the former than the latter variety. The differential nitrogen utilization efficiency in these varieties may be potentially used as measure of sensitivity characteristics in breeding programs for yield improvement in mustard under the present trend of increase in O(3) concentrations. PMID- 22072446 TI - Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements. AB - Osteoporosis is typically diagnosed by dual-energy X-ray absorptiometry (DXA) measurements of areal bone mineral density (aBMD). Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), may increase the diagnostic accuracy of DXA and enhance our mechanistic understanding of decreased bone strength in osteoporosis. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA, trabecular plate and rod microarchitecture measured by HR-pQCT image-based individual trabecula segmentation (ITS) analysis, and whole bone and trabecular bone stiffness by microfinite element analysis (uFEA) of HR-pQCT images at the radius and tibia. DXA T-scores were similar in women with and without fractures at the spine, hip, and 1/3 radius, but lower in fracture subjects at the ultradistal radius. Trabecular microarchitecture of fracture subjects was characterized by preferential reductions in trabecular plate bone volume, number, and connectivity over rod trabecular parameters, loss of axially aligned trabeculae, and a more rod-like trabecular network. In addition, decreased thickness and size of trabecular plates were observed at the tibia. The differences between groups were greater at the radius than the tibia for plate number, rod bone volume fraction and number, and plate-rod and rod-rod junction densities. Most differences between groups remained after adjustment for T-score by DXA. At a fixed bone volume fraction, trabecular plate volume, number, and connectivity were directly associated with bone stiffness. In contrast, rod volume, number, and connectivity were inversely associated with bone stiffness. In summary, HR-pQCT-based ITS and uFEA measurements discriminate fracture status in postmenopausal women independent of DXA measurements. Moreover, these results suggest that preferential loss of plate-like trabeculae contribute to lower trabecular bone and whole bone stiffness in women with fractures. We conclude that HR-pQCT-based ITS and uFEA measurements increase our understanding of the microstructural pathogenesis of fragility fracture in postmenopausal women. PMID- 22072447 TI - Aerial shaking performance of wet Anna's hummingbirds. AB - External wetting poses problems of immediate heat loss and long-term pathogen growth for vertebrates. Beyond these risks, the locomotor ability of smaller animals, and particularly of fliers, may be impaired by water adhering to the body. Here, we report on the remarkable ability of hummingbirds to perform rapid shakes in order to expel water from their plumage even while in flight. Kinematic performance of aerial versus non-aerial shakes (i.e. those performed while perching) was compared. Oscillation frequencies of the head, body and tail were lower in aerial shakes. Tangential speeds and accelerations of the trunk and tail were roughly similar in aerial and non-aerial shakes, but values for head motions while perching were twice as high when compared with aerial shakes [corrected] . Azimuthal angular amplitudes for both aerial and non-aerial shakes reached values greater than 180 degrees for the head, greater than 45 degrees for the body trunk and slightly greater than 90 degrees for the tail and wings. Using a feather on an oscillating disc to mimic shaking motions, we found that bending increased average speeds by up to 36 per cent and accelerations of the feather tip up to fourfold relative to a hypothetical rigid feather. Feather flexibility may help to enhance shedding of water and reduce body oscillations during shaking. PMID- 22072449 TI - How to identify water from thickener aqueous solutions by touch. AB - Water detection is one of the most crucial psychological processes for many animals. However, nobody knows the perception mechanism of water through our tactile sense. In the present study, we found that a characteristic frictional stimulus with large acceleration is one of the cues to differentiate water from water contaminated with thickener. When subjects applied small amounts of water to a glass plate, strong stick-slip phenomena with a friction force of 0.46 +/- 0.30 N and a vertical force of 0.57 +/- 0.36 N were observed at the skin surface, as shown in previous studies. Surprisingly, periodic shears with acceleration seven times greater than gravitational acceleration occurred during the application process. Finite-element analyses predicted that these strong stimuli could activate tactile receptors: Meissner's corpuscle and Pacinians. When such stimuli were applied to the fingertips by an ultrasonic vibrator, a water-like tactile texture was perceived by some subjects, even though no liquid was present between the fingertip and the vibrator surface. These findings could potentially be applied in the following areas: materials science, information technology, medical treatment and entertainment. PMID- 22072450 TI - Population structure in the Neisseria, and the biological significance of fuzzy species. AB - Phenotypic and genetic variation in bacteria can take bewilderingly complex forms even within a single genus. One of the most intriguing examples of this is the genus Neisseria, which comprises both pathogens and commensals colonizing a variety of body sites and host species, and causing a range of disease. Complex relatedness among both named species and previously identified lineages of Neisseria makes it challenging to study their evolution. Using the largest publicly available collection of bacterial sequence data in combination with a population genetic analysis and experiment, we probe the contribution of inter species recombination to neisserial population structure, and specifically whether it is more common in some strains than others. We identify hybrid groups of strains containing sequences typical of more than one species. These groups of strains, typical of a fuzzy species, appear to have experienced elevated rates of inter-species recombination estimated by population genetic analysis and further supported by transformation experiments. In particular, strains of the pathogen Neisseria meningitidis in the fuzzy species boundary appear to follow a different lifestyle, which may have considerable biological implications concerning distribution of novel resistance elements and meningococcal vaccine development. Despite the strong evidence for negligible geographical barriers to gene flow within the population, exchange of genetic material still shows directionality among named species in a non-uniform manner. PMID- 22072452 TI - Operation of the alula as an indicator of gear change in hoverflies. AB - The alula is a hinged flap found at the base of the wings of most brachyceran Diptera. The alula accounts for up to 10 per cent of the total wing area in hoverflies (Syrphidae), and its hinged arrangement allows the wings to be swept back over the thorax and abdomen at rest. The alula is actuated via the third axillary sclerite, which is a component of the wing hinge that is involved in wing retraction and control. The third axillary sclerite has also been implicated in the gear change mechanism of flies. This mechanism allows rapid switching between different modes of wing kinematics, by imposing or removing contact with a mechanical stop limiting movement of the wing during the lower half of the downstroke. The alula operates in two distinct states during flight-flipped or flat-and we hypothesize that its state indicates switching between different flight modes. We used high-speed digital video of free-flying hoverflies (Eristalis tenax and Eristalis pertinax) to investigate whether flipping of the alula was associated with changes in wing and body kinematics. We found that alula state was associated with different distributions of multiple wing kinematic parameters, including stroke amplitude, stroke deviation angle, downstroke angle of incidence and timing of supination. Changes in all of these parameters have previously been linked to gear change in flies. Symmetric flipping of the alulae was associated with changes in the symmetric linear acceleration of the body, while asymmetric flipping of the alulae was associated with asymmetric angular acceleration of the body. We conclude that the wings produce less aerodynamic force when the alula is flipped, largely as a result of the accompanying changes in wing kinematics. The alula changes state at mid downstroke, which is the point at which the gear change mechanism is known to come into effect. This transition is accompanied by changes in the other wing kinematic parameters. We therefore find that the state of the alula is linked to the same parameters as are affected by the gear change mechanism. We conclude that the state of the alula does indeed indicate the operation of different flight modes in Eristalis, and infer that a likely mechanism for these changes in flight mode is the gear change mechanism. PMID- 22072453 TI - Ultrasonographic findings in cubital tunnel syndrome caused by a cubitus varus deformity. AB - We have retrospectively reviewed the clinical, preoperative ultrasonographic, and operative findings of eight patients who had tardy ulnar nerve palsy caused by a cubitus varus deformity. The mean varus angle on the affected side was 23 degrees . With preoperative ultrasonography, the anterior dislocation of the ulnar nerve from the medial epicondyle was detected in dynamic scanning of short-axis images, and long-axis images revealed nerve compression and kinking in the proximal border of the flexor carpi ulnaris. Operative findings revealed compression of the ulnar nerve by a fibrous band, which was released in all cases. The cause of the tardy ulnar nerve palsy in this series of patients was constriction by a fibrous band and kinking in the proximal border of the flexor carpi ulnaris due to ulnar nerve dislocation from compression resulting from the forward movement of the medial head of the triceps brachii muscle. PMID- 22072451 TI - Predicting the effect of climate change on African trypanosomiasis: integrating epidemiology with parasite and vector biology. AB - Climate warming over the next century is expected to have a large impact on the interactions between pathogens and their animal and human hosts. Vector-borne diseases are particularly sensitive to warming because temperature changes can alter vector development rates, shift their geographical distribution and alter transmission dynamics. For this reason, African trypanosomiasis (sleeping sickness), a vector-borne disease of humans and animals, was recently identified as one of the 12 infectious diseases likely to spread owing to climate change. We combine a variety of direct effects of temperature on vector ecology, vector biology and vector-parasite interactions via a disease transmission model and extrapolate the potential compounding effects of projected warming on the epidemiology of African trypanosomiasis. The model predicts that epidemics can occur when mean temperatures are between 20.7 degrees C and 26.1 degrees C. Our model does not predict a large-range expansion, but rather a large shift of up to 60 per cent in the geographical extent of the range. The model also predicts that 46-77 million additional people may be at risk of exposure by 2090. Future research could expand our analysis to include other environmental factors that influence tsetse populations and disease transmission such as humidity, as well as changes to human, livestock and wildlife distributions. The modelling approach presented here provides a framework for using the climate-sensitive aspects of vector and pathogen biology to predict changes in disease prevalence and risk owing to climate change. PMID- 22072454 TI - Continuous peripheral nerve block in forearm for severe hand trauma. AB - We studied the use of a continuous peripheral nerve block (CPNB) in the distal forearm and wrist immediately after emergent surgery for severe hand trauma in 22 hands. After emergent surgery, a 2-3 cm longitudinal incision was made at the distal forearm and an 18-gauge catheter was inserted along the peripheral nerves. All patients received postoperative analgesia by continuous infusion of 0.2% ropivacaine at 2 ml/h for seven to 21 days. Pain score remained low during postoperative period and only a small number of analgesic rescues were needed. There were no major complications related to the CPNB and one patient showed mild superficial infection at the insertion site that immediately recovered after catheter removal. This method provides good postoperative analgesia without loss of motor function in extrinsic hand muscles and should be considered as a postoperative pain management for severe hand trauma. PMID- 22072455 TI - The flexor carpi radialisbrevis muscle - an anomaly in forearm musculature: a review article. AB - The volar approach to the distal radius is an increasingly popular method of exposing fractures of the distal radius for purposes of reduction and internal fixation. We present five clinical cases and one cadaveric case of an incidental finding of an aberrant flexor of the forearm. A literature review undertaken showed few previous case reports of this relatively uncommon anatomic variant. The possibility of seeing the flexor carpi radialis brevis muscle during a volar approach to the distal radius should be made known to all orthopedic and hand surgeons. PMID- 22072456 TI - Wrist denervation in isolation: a prospective outcome study with patient selection by wrist blockade. AB - Surgical wrist denervation involves division of the anterior and posterior interosseous nerves and articular branches of the superficial radial nerve. In this outcome study, 37 patients were individually assessed and deemed suitable for denervation surgery due to appreciable symptom resolution following a local anesthetic wrist block. At a mean of 18 months following denervation surgery, median activity pain scores had decreased by 60% (p < 0.001) from initial assessment levels, and more than three quarters (30/37) of patients reported continued improvement in their activity pain (p < 0.001). More than two thirds of patients had a satisfaction VAS of greater than 50, with less postoperative resting pain and a greater reduction in postoperative activity pain as the important predictors of patient satisfaction. Thirty-one out of the 37 patients had not represented to our department for revision wrist surgery by a mean of 10.3 years follow-up. We have found this procedure useful in ameliorating symptoms for some patients who would conventionally have required partial or total wrist fusions with greater residual functional limitation. PMID- 22072457 TI - Accurate radiographic measurement of the distal radial tilt. AB - Both wrists in 189 patients who had been treated for dorsally displaced distal radius fracture were X-rayed with both right angle and 15 degrees tilted lateral views. Two investigators measured the radial tilt. The mean difference in the angles recorded by the two investigators was 2.5 degrees for the tilted and 3.7 degrees for the right angle projections (p = 4.7 * 10(-8)). The precision of the method was 2.6 degrees for the tilted and 3.5 degrees for right angle projection. The mean angle measured on the tilted views was 3 degrees more dorsal than on the right angle views for wrists with a volar tilt between 10 degrees and 15 degrees , and 0 degrees to 2 degrees for wrists with less volar tilt or dorsal displacement. Lateral projections tilted 15 degrees allow more precise measurements than right angle views. Correction is not necessary when comparing to right angle views, as long as there is displacement in a dorsal direction of the distal fragment. PMID- 22072458 TI - Locking palmar plate fixation for dorsally displaced fractures of the distal radius: a preliminary report. AB - We reviewed a series of 62 consecutive patients with dorsally displaced fractures of the distal radius, including 20 extra-articular and 42 intra-articular fractures. All patients were treated with palmar locking plate systems at our institution between 2002 and 2006. After a minimum follow-up time of 12 weeks, the fractures had healed with satisfactory radiographic and functional results. According to the demerit point system of Gartland and Werley, 35 patients were rated excellent, 26 good, and one fair. In the good and fair groups, the demerit points were almost all for ulnar wrist pain. Our results suggest that palmar locking plate systems enable early functional mobilization with good reproducible radiographic and clinical outcomes. Since nine out of 62 patients had residual ulnar wrist pain at the final follow-up evaluation, further investigation of the pathogenesis of ulnar wrist pain is necessary to obtain better functional outcomes. PMID- 22072459 TI - Prevention of flexor pollicis longus tendon rupture after volar plate fixation of distal radius fractures. AB - We evaluated the presence of "tendon irritation" of flexor pollicis longus (FPL) for cases of distal radius fracture treated with volar plates to prevent FPL tendon rupture. This report details cases of 24 patients. The presence of pain or a sense of incompatibility and subdermal crepitus around the wrist with an active thumb motion were defined as symptoms of FPL tendon irritation. Twelve of 24 patients complained of FPL tendon irritation. The plates were removed in nine of these 12 patients, while tendon injury was found in three cases. The other 12 patients did not complain of FPL tendon irritation. Four of these 12 patients underwent plate removal, and tendon injury was not detected. The results of this study indicate that FPL tendon irritation is likely to appear before tendon rupture. Therefore, FPL tendon rupture might be prevented by plate removal in patients who complained of tendon irritation. PMID- 22072460 TI - Clinical outcomes of excision arthroplasty for Kienbock's disease. AB - We have carried out a replacement of the lunate in 12 patients with advanced Kienbock's disease, with excision of the lunate and insertion of an iliac bone flap wrapped into palmaris longus. The aims of this study were to determine the effect of this procedure for advanced Kienbock's disease. At a mean follow-up period of 45.3 months, the mean clinical score was excellent in all cases. Radiographically, progression of osteoarthritis (OA) in the radiocarpal joint was found in two patients. At follow-up, the X-ray findings indicated a reduced of osseous core in four patients. On the other hand, carpal height ratio showed no significant change at follow-up. Excision arthroplasty using a tendon ball with osseous core for advanced Kienbock's disease leads to OA progression in some cases. However, clinical results were excellent in all cases. Therefore, this current study provides effective therapeutic procedure for advanced Kienbock's disease. PMID- 22072461 TI - Macromastia: a risk factor for carpal tunnel syndrome? AB - PURPOSE: To evaluate the prevalence of carpal tunnel syndrome (CTS) in a cohort of women with macromastia and to assess the evolution of the CTS signs and symptoms after breast surgery. POPULATION: A series of 123 women was evaluated. CTS was defined by co-existence of symptoms, two physical findings and electrophysiological evaluation. One year after reduction mammaplasty, the 22 patients who had been diagnosed CTS were re-evaluated. RESULTS: CTS group of women had a mean age of 38.8 years, mean body mass index of 28.5 kg/m(2) and mean breast size of 35.9 cm. Age and nipple-to-sternal notch distance were statistically significantly associated with CTS (p = 0.001 and p = 0.001, respectively). A year after surgery 15 patients were re-assessed: nine patients reported absence or improvement of CTS symptoms while six patients reported symptoms persistence or worsening. CONCLUSION: Age, breast size, but not body mass index, have a positive correlation with the CTS. PMID- 22072462 TI - High definition ultrasound as diagnostic adjunct for incomplete carpal tunnel release. AB - Carpal tunnel syndrome is the most common nerve entrapment in the upper limb and carpal tunnel release (CTR) provides the most predictable outcome and relief of symptoms. Incomplete carpal tunnel releases are uncommon, however, in the event of incomplete surgical releases, symptoms following such incomplete releases tend to be more severe than the symptoms presented at the initial complaint. We present our experience in utilizing high definition ultrasound to reliably and accurately localize the anatomical cause to aid focused revision CTR. PMID- 22072463 TI - Opponoplasty without postoperative immobilization. AB - Opponoplasty using tendon transfer is a useful reconstructive procedure that restores lost thenar muscle function. Tendon transfers, however, require postoperative immobilization periods of up to four weeks before the sutured tendons reach required strength. We developed an opponoplasty procedure using alpha-TCP (alpha-tricalcium phosphate) cement that does not require postoperative immobilization and was applied to nine hands out of nine cases. The procedure is performed under local anesthesia without a pneumatic tourniquet and on an outpatient basis. In this procedure, the flexor digitorum superficialis of the ring finger is used as the donor tendon and the palmaris longus tendon is used as a dynamic pulley. The distal end of the transferred tendon is anchored to the inside of a newly formed bone hole in the thumb's proximal phalanx using alpha TCP cement. Our opponoplasty procedure was uneventful postoperatively and produced satisfactory results in all nine cases. The alpha-TCP cement procedure shows potential for other tendon transfer applications. PMID- 22072464 TI - Outcomes of silastic trapezium replacements. AB - Trapezio-metacarpal joint arthritis is common, affecting 7% of men and 15% of women. Numerous surgical techniques are described for this condition but it is not clear which is best. Eighty-six silicone trapezium replacements were assessed at an average of 46 months (six to 156 months) postoperatively for patient satisfaction, pain, key and power grip strength, range of motion, complications and disability with DASH score. Patient satisfaction was 92%. There was excellent pain reduction from 4.2 to 0.6 on a scale of 0 to 5. Strength was 72% and 84% of age-sex-matched normal data for key and power grips, respectively. The complication rate was low, with two cases of persistent pain. One resolved spontaneously, the other resolved following revision of the silicone implant. The average DASH score was 30. Silicone trapezium replacement is an effective operation that offers the patient good pain relief, strength and good function with few complications. PMID- 22072465 TI - Hand infection in diabetic patients. AB - The diabetic hand infection is less reported in the literature. Therefore, it is easily ignored and underestimated resulting in increased morbidity among the diabetic population. Diabetic hand is a rapid in progression, extensive and severe tissue destruction. We analyze the clinical course and outcome of hand infection in diabetic patients. We reviewed all the admissions with hand infection from January 2006-April 2010. Thirty-seven patients were found with associated diabetes mellitus. The demographic data, culture report, number of operations and management, hospital stay and outcome-like amputation were recorded. The average age was 62 years. Pain and swelling were the chief complaints. The cause of infection was varied. The infection was superficial in 13 and deep in 24 patients. Forty-one percent of culture report revealed polymicrobial organism. The increased length of hospital stay, reoperations and amputation were associated with deep infection and polymicrobial organism. Prompt medical and surgical attentions are the most important factors. A proper glycemic control, elevation of the affected extremity, thorough and adequate surgical debridement and appropriate antibiotics are the important considerations when dealing with diabetic hand infection. PMID- 22072466 TI - Proximal phalanx injection for trigger finger: randomized controlled trial. AB - Trigger finger is one of the most common upper extremity problems in the outpatient department. Conservative treatment is the mainstay for management of trigger digits especially steroid injection with highly satisfactory outcome and minimal complication. Conventional injection technique (CI) that approaches flexor tendon sheath over metacarpal head directly causes pain for most patients. The proximal phalanx injection technique (P1I) at palmar surface of midproximal phalanx is simple and less painful for the patients. We compared pain result and effectiveness between these two methods. Forty patients with primary trigger fingers were placed in a prospective randomized study to receive steroid injection with either the CI or P1I techniques. Demographic data were recorded. Immediately after the injection, pain score was recorded for each patient using the pain visual analog scale. The patients were followed every month for three months to determine recurrent symptoms. Student's t-test, chi-square and Fisher's exact test were used for data analysis. The mean pain VAS scores immediately post injection were 7.3 +/- 1.3 and 3.2 +/- 2.2 in the CI and P1I techniques, respectively. The P1I technique group had a significantly lower pain score than CI technique group (p < 0.001). The recurrence rate was 15% in the CI technique when compared to 25% in the P1I technique which was not significant (p = 0.685). We concluded that the P1I technique is less painful than the CI technique without any significant difference in recurrence rate between the two groups at three months follow-up. PMID- 22072467 TI - Suppurative arthritis involving the synchondrosis of an os acromiale. AB - Os acromiale is an unfused epiphysis of the anterior part of the acromion occurring in approximately 8% of the population. Infection of this joint has not been previously described in the literature. We report such a case in a 59-year old woman presenting with shoulder pain. A high index of clinical suspicion, with early imaging of the shoulder leading to prompt and definitive diagnosis, can lead to appropriate treatment and produce a favorable outcome. PMID- 22072468 TI - Intramedullary nailing for pathological fractures of the ulna. AB - Pathological lesions of long bones increase the morbidity of many common cancers. The orthopedic management of metastatic skeletal lesions can be challenging. The ultimate aim is to provide patients with a painless, functional limb. We present a report of two cases were a novel minimally invasive long bone nailing technique has been utilized to achieve skeletal stability and alleviation of symptoms. PMID- 22072469 TI - Remodeling of distal ulna after excision arthroplasty for acute comminuted distal ulnar fracture: a case report. AB - Bone adaptation after excision arthroplasty of distal radioulnar joint in an acute traumatic distal ulna fracture has never been reported. A case of irreparable and comminuted distal ulnar head fracture was managed by excising the ulna head and repairing the fovea (deep ligament) attachments of distal radioulnar ligaments, and then an unexpected remodeling of the distal ulna with the shape of pole and seat was noted. The anatomy of deep fibers of distal radioulnar ligament is important not only in biomechanics about the stability of distal radioulnar joint but it is also possible in the morphology about the shape of the distal radioulnar joint. PMID- 22072470 TI - Double plate fixation for correction of the malunited distal ulna fracture: a case report. AB - A 62-year-old woman visited our hospital one year after a motor vehicle accident complaining of ulnar wrist pain and restricted pronation and supination. Radiographs showed a 35 degrees angular deformity at the ulnar neck. Closing wedge osteotomy was performed using two plates for stabilization. Twenty-four months postoperatively, the osteotomy site united without correction loss and the patient gained adequate pronation and supination. To the best of our knowledge, this represents the first report of corrective osteotomy for the treatment of malunited ulnar neck fracture. Although salvage operations such as ulnar head resection and the Sauve-Kapandji procedure may provide reasonable results, anatomical repair can be considered as an option. PMID- 22072471 TI - Carpal tunnel syndrome caused by a ganglion in the carpal tunnel with an atypical type of palsy: a case report. AB - Carpal tunnel syndrome caused by a ganglion is a rare condition. We report a case which presented with a rapidly progressive onset of symptoms and subsequent thenar palsy. PMID- 22072472 TI - Median nerve palsy: a complication of brachial artery cardiac catheterization. AB - The patient, an 83-year-old male with ischemic cardiac disease, was examined using a periodical left brachial artery cardiac catheterization. Six hours after the examination, complete median nerve palsy appeared. Four months later, the median nerve was explored and found to be compressed by a hematoma in the brachial artery. The location of the hematoma was at 6 cm proximal to the puncturing point, because the catheter may have penetrated the brachial artery from the lumen. The median nerve was released and the hematoma removed. One year after surgery, the median nerve palsy had disappeared. PMID- 22072473 TI - Closed radial wedge osteotomy for Preiser's disease: a report of four cases. AB - PURPOSE: To investigate the clinical outcome of closed radial wedge osteotomy (CRWO) for Preiser's disease. METHODS: CRWO was performed for four patients with Preiser's disease between 2000 and 2005. All patients were diagnosed by X-ray and magnetic resonance imaging (MRI) scans. Separation gaps in the radioscaphoid joint were observed to evaluate the decompression in the area. Clinical evaluation was performed using Cooney's scoring system. RESULTS: Although wrist pain persisted in patients with radioscaphoid arthritis change, marked mitigation of wrist pain was confirmed in three patients. The average clinical score was 66, with good in one, fair in two, and poor in one. Restriction of wrist movement by CRWO caused lower clinical scores. No patients had wrist arthrodesis at the last follow-up evaluation. CONCLUSIONS: Short-term observation showed disappointing clinical results; however, for relief of wrist pain, this method is a potential surgical procedure for Preiser's disease under limited conditions. PMID- 22072474 TI - Isolated complete volar dislocation of the capitate: a case report. AB - Total dislocation of the capitate is an extremely rare event. We report on one such unusual case. The complete expulsion of the capitate from its physiological position is difficult to diagnose. Standard parameters of the antero-posterior and lateral radiological do not head to a definite diagnosis. In our patient, the only real diagnostic tool was the clinical assessment and the Gilula arches alteration to the standard antero-posterior projection. In the period following trauma, the patient reported a very high level of pain in the wrist. Since this could not be correlated to the lesions that had been diagnosed, we hypothesized the presence of any carpal bones damage. A definite diagnosis was obtained at CT scan, which also revealed the absence of any fractures. PMID- 22072475 TI - Free fibular graft reconstruction following resection of chondrosarcoma in the first metacarpal. AB - Chondrosarcoma is most frequently present in the pelvis and long bones and rarely seen in the bones of the hand. Traditionally the treatment of choice for involvment of the hand is ray amputation, however this causes significant functional deficit if there is thumb involvement. There are limited cases in literature of resection of thumb chondrosarcoma with restoration of function. We present a case of high grade chondrosarcoma of the first metacarpal treated with resection and free fibular graft reconstruction. We report excellent functional outcome with this procedure. PMID- 22072476 TI - Reconstruction of the thumb with a modified wrap-around flap in a patient suffering from beta-thalassemia minor. AB - Thalassemia is a congenital hemolytic disorder caused by a partial or complete deficiency of alpha- or beta-globin chain synthesis. It has been seen that thalassemic patients exhibit an increased frequency of thrombotic events. The article presents the first case of thumb reconstruction with a modified wrap around flap in a patient suffering from beta-thalassemia minor. PMID- 22072477 TI - Multiple localized giant cell tumor of the tendon sheath (GCTTS) affecting a single tendon: a very rare case report and review of recent cases. AB - INTRODUCTION: Giant cell tumors of the tendon sheath (GCTTS) are very common. More recently, a small number of case reports have identified the presence of multifocal GCTTS in the hand. These case reports have identified the presence of a maximum of two simultaneous lesions of a giant cell tumor affecting the same tendon sheath. We present an exceptionally rare case of simultaneous multiple localized GCTTS in which five lesions were identified on a single tendon simultaneously. This number of lesions on a single tendon has never been previously reported. CASE: A 37-year-old tree surgeon initially complained of pain in the region of the base of the ring and little fingers. A month later, he developed multiple soft tissue swellings at these sites and a soft tissue mass in the center of the palm relating to the left ring finger. A magnetic resonance imaging (MRI) scan suggested multiple GCTTS. These masses were excised completely without MRI evidence of a recurrence. Multiple GCTTS should be a differential diagnosis of multiple soft tissue swellings in the hand with an MRI scan and complete excision being the appropriate imaging and treatment modality respectively. PMID- 22072478 TI - Closed traumatic rupture of both extensor tendons of the index finger in zone VI: a case report. AB - The patient with closed traumatic rupture of both extensor tendons of the index finger in zone VI was described. PMID- 22072479 TI - Distal phalangeal reconstruction for recurrent intraosseous epidermoid cyst of the finger - a case report. AB - Intraosseous epidermoid cyst of the finger phalanx is rare. We report a case of postoperative recurrent intraosseous epidermoid cyst of the distal phalanx of the ring finger. To prevent further recurrence while maintaining morphology and function, the distal half of the distal phalanx that included the epidermoid cyst was resected to completely remove the lesion. The distal phalanx was then reconstructed by grafting corticocancellous bone from the ilium and shaped into a distal phalanx. The operation was performed using a through-the-nail approach, temporarily removing the nail and placing a longitudinal incision in the nail bed to approach the phalanx. Postoperatively, bone fusion was achieved without recurrence and the shape of the distal phalanx was normal. Distal phalangeal hypertrophy and nail plate deformity also normalized and excellent results were obtained. PMID- 22072480 TI - The "local dorsal adipofascial flap" for volar digital defects: a case report. AB - The coverage of volar digital defects can be achieved by a variety of surgical options. Although frequently used and reliable, these procedures entail the need for a second stage for flap release, meticulous dissection, sacrifice of a digital artery of the uninvolved digit, or delayed mobilization resulting in digital stiffness. The ideal surgical procedure for such defects should be a simple, single-stage surgery that allows early mobilization and return to function and at the same time avoiding unnecessary donor site morbidity from an uninvolved digit. The "local dorsal adipofascial flap" is a simple procedure that does not need a secondary procedure for flap release and affords early range of motion and return to function. We used this new flap technique in two digits with volar defects in a single patient. At ten months after flap coverage, the fingers were fully functional with good healing of the "local dorsal adipofascial flap." PMID- 22072481 TI - Nail hypertrophy after elective surgery on the little finger: a case report. AB - The authors present a case that developed acute painful nail hypertrophy of the ipsilateral four fingers which resembled finger clubbing after undergoing elective hand surgery on the little finger. The patient was diagnosed as having complex regional pain syndrome (CRPS), and the nail hypertrophy subsided gradually on pain control, and completely normalized one year after onset. Recognizing this phenomenon may help initiate early treatment for CRPS and avoid unnecessary antibiotic or antifungal medications for postoperative infection. PMID- 22072482 TI - Triangular flaps: a modified technique for the correction of congenital constriction ring syndrome. AB - Congenital constriction ring syndrome (CCRS) is a congenital anomaly with a wide spectrum of clinical presentation. The accepted method of correcting a circular constriction is to excise the deep part of the constriction, and break the line of the circular scar with multiple Z- or W-plasties. Specific correction of soft tissue is recommended concurrently, to better correct the "sandglass" deformity. Here we describe a new technique using triangular advancement flaps to correct the deformity in eight patients with constriction ring syndrome, involving either the upper or lower limbs. In this technique, triangular flaps can be introduced either proximal or distal to the ring, depending on the limb circumference, to correct the contour deformity. In all eight patients, a normal extremity contour was obtained, with complete elimination of the deformity caused by the constriction ring. A mean follow-up of 43 months revealed an aesthetically acceptable scar, with no case of recurrence. Triangular flaps designed either proximal or distal to the constriction ring is able to correct the contour deformity of the limbs with great versatility and acceptable aesthetic results. PMID- 22072483 TI - Digital artery perforator flap for reconstruction of fingertip after resection of melanoma in situ. AB - A case of 40-year-old female with melanoma in situ on her left index finger is presented. When treating melanoma in situ, it is recommended to have 3 mm margin and to include subcutaneous fat layer for resection of the tumor. To reconstruct the fingertip with the exposed distal phalanx, we used digital artery perforator flap. Since the resection of melanoma in situ in the appropriate manner would result in low risk of recurrence of the tumor, unlike melanoma of more deeply infiltrating types, it is important to use flaps which are easy to raise, functionally superior, and cosmetically excellent, The drawbacks of using digital artery perforator flap is that the operator is not able to tell if the flap includes the perforator until the flap is raised, since there is a risk of damaging the perforator when trying to expose it to visually confirm that it is included in the flap. PMID- 22072484 TI - Consenting for the application of tourniquet in young female patients with hand and wrist injuries who have a contraceptive implant. PMID- 22072485 TI - Prognostication in primary myelofibrosis. AB - Primary myelofibrosis (PMF) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm usually affecting elderly people. Median survival currently approaches 6 years, with a few patients surviving more than 20 years but others dying soon after diagnosis. In 10% to 20% of patients, PMF evolves into acute leukemia. Conventional treatment is merely palliative and does not prolong survival. The only chance for cure is allogeneic hemopoietic stem-cell transplantation (allo-HSCT), which is associated with high morbidity and mortality. Introduction of less aggressive forms of allo-HSCT and the prospect of molecular-targeted therapies has renewed interest in prognostication in PMF. The most important prognostic factors are anemia, age over 65 years, constitutional symptoms, leukocytosis, blood blasts, and some cytogenetic abnormalities. These factors have recently been systematized into an International Prognostic Scoring System (IPSS) and further refined in a dynamic IPSS (DIPSS), useful at any time over the disease course, as well as a DIPSS-plus model including karyotypic information. PMID- 22072486 TI - Development of a double-layer microfluidic chip with flow medium for chemotherapy resistance analysis of lung cancer. AB - Integration and miniaturization are main advantages of microchip-based systems. Vertical integration of the multiple operations within a multiple-layer chip is expected to satisfy the urgent demand for high-throughput and large-scale applications. This study aimed at establishing a double-layer chip to integrate the operations including the cell culture, the identification of the protein and the detection of the cell viability onto a platform systematically and supplied with flow fresh medium continuously via a syringe pump to mimic the microenvironment in vivo. With this device, human non-small cell lung cancer cell line (SPCA-1) was cultured well; the expression and the activity of multidrug resistance-associated protein (MRP1) were detected by immunofluorescence assay for the cells pretreated with or without MK-571, a known inhibitor of MRP1; apoptosis percentages were assayed for the cells after being treated by the anticancer drug etoposide (VP-16). The results demonstrated that the function of the MRP1 was inhibited by MK-571, and the percentage of apoptotic for the cells pretreated with MK-571 was higher than that of the control (38.2+/-2.5% versus 12.3+/-0.85%, p<0.005). All these indicated that the new device could provide a suitable condition for cell culture and functional analysis in biomedical research, and MK-571 is an effective inhibitor of MRP1 associated with the viability of SPCA-1 cell line treated by VP-16. PMID- 22072487 TI - [How to better understand magnetic resonance tomography, recognise risks for blindness, evaluate contrast vision and correct a glaucoma myth]. PMID- 22072488 TI - [Magnetic resonance imaging in neuro-ophthalmological diagnostics]. AB - Magnetic resonance imaging has become the most important tomographic imaging technique in neuro-ophthalmological diagnostics. A short introduction to the basic physical principles of MRI followed by a glossary summarising the relevant sequences used in neuro-ophthalmologic diagnostics provides an insight into this complex method. Differences and specific diagnostic values of every sequence are demonstrated with the help of sample images. PMID- 22072489 TI - [Experience in contrast vision testing]. AB - INTRODUCTION: Since July 2011 driving licensing in Germany requires contrast vision to be tested. Recommendations are available for testing under mesopic conditions only. This study is aimed to provide recommendations for photopic testing. METHOD: 169 persons were tested both under mesopic (Mesotest) and photopic (Optovist) conditions. RESULTS: With the Mesotest the setting without glare and the requirement to recognize contrast 1:5 or with glare contrast 1:23 proved to be suitable. With the Optovist visual acuity size 0.4 without and 0.25 with glare proved to be adequate, if the requirement is to recognize the limit of 5 %. DISCUSSION: Not unexpectedly, there is no perfect congruence between the tests. We therefore recommend that the screening methods used in industrial medicine need to be sufficiently sensitive and specific, unfortunately this is met only by some of the conditions supplied with the instruments. PMID- 22072490 TI - [Tongue necrosis as first clinical manifestation of Horton giant cell arteritis]. PMID- 22072491 TI - Neoplastic MiR-17~92 deregulation at a DNA fragility motif (SIDD). AB - Chromosomal or mutational activation of BCL6 (at 3q27) typifies diffuse large B cell lymphoma (DLBCL) which in the germinal center subtype may be accompanied by focal amplification of chromosome band 13q31 effecting upregulation of miR-17~92. Using long distance inverse-polymerase chain reaction, we mapped and sequenced six breakpoints of a complex BCL6 rearrangement t(3;13)(q27;q31)t(12;13)(p11;q31) in DLBCL cells, which places miR-17~92 antisense within the resulting ITPR2-BCL6 chimeric fusion gene rearrangement. MiR-17~92 members were upregulated ~15-fold over controls in a copy number independent manner consistent with structural deregulation. MIR17HG and ITPR2-BCL6 were, despite their close configuration, independently expressed, discounting antisense regulation. MIR17HG in t(3;13)t(12;13) cells proved highly responsive to treatment with histone deacetylase inhibitors implicating epigenetic deregulation, consistent with which increased histone-H3 acetylation was detected by chromatin immunoprecipitation near the upstream MIR17HG breakpoint. Remarkably, 5/6 DNA breaks in the t(3;13)t(12;13) precisely cut at stress-induced DNA duplex destabilization (SIDD) peaks reminiscent of chromosomal fragile sites, while the sixth lay 150 bp distant. Extended SIDD profiling showed that additional oncomiRs also map to SIDD peaks. Fluorescence in situ hybridization analysis showed that 11 of 52 (21%) leukemia-lymphoma (L-L) cell lines with 13q31 involvement bore structural rearrangements at/near MIR17HG associated with upregulation. As well as fueling genome instability, SIDD peaks mark regulatory nuclear-scaffold matrix attachment regions open to nucleosomal acetylation. Collectively, our data indict a specific DNA instability motif (SIDD) in chromosome rearrangement, specifically alterations activating miR-17~92 epigenetically via promoter hyperacetylation, and supply a model for the clustering of oncomiRs near cancer breakpoints. PMID- 22072492 TI - Phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in patients with low or intermediate-1 risk myelodysplastic syndrome. PMID- 22072493 TI - Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study. AB - A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 35-70 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.46 0.95) and TRAP (adjusted HR 0.61; 95%CI (0.43-0.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.22-0.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.28-0.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.21-0.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC. PMID- 22072495 TI - (E)- and (Z)-beta-borylallylsilanes by alkyne silaboration followed by regio- and stereoselective double-bond migration. AB - Double take: beta-Borylallylsilanes have been synthesized by the regioselective silaboration of terminal alkynes followed by palladium-catalyzed double-bond migration of the resulting beta-borylalkenylsilanes. The stereoselectivity of the double-bond migration can be controlled by additives, thus leading to the stereocomplementary synthesis of (E)- and (Z)-beta-borylallylsilanes. PMID- 22072494 TI - Androgen deprivation and thromboembolic events in men with prostate cancer. AB - BACKGROUND: Androgen deprivation therapy (ADT) improves prostate cancer outcomes in specific clinical settings, but is associated with adverse effects, including cardiac complications and possibly thromboembolic complications. The objective of this study was to estimate the impact of ADT on thromboembolic events (TEs) in a population-based cohort. METHODS: In the linked Surveillance, Epidemiology and End Results-Medicare database, we identified men older than 65 who were diagnosed with nonmetastatic prostate cancer between 1999 and 2005. Medical or surgical ADT was identified by Medicare claims for gonadotropin-releasing hormone agonists or bilateral orchiectomy at any time following diagnosis. TEs included deep venous thrombosis, pulmonary embolism, and arterial embolism. The impact of ADT on the risk of any TE and on total number of events was estimated, controlling for patient and tumor characteristics. RESULTS: Of 154,611 patients with prostate cancer, 58,466 (38%) received ADT. During a median follow-up of 52 months, 15,950 men had at least 1 TE, including 8829 (55%) who had ADT and 7121 (45%) with no ADT. ADT was associated with increased risk of a TE (adjusted hazard ratio = 1.56; 95% confidence interval, 1.50-1.61; P < .0001), and duration of ADT was associated with the total number of events (P < .0001). CONCLUSIONS: In this population-based cohort, ADT was associated with increased risk of a TE, and longer durations of ADT were associated with more TEs. Men with intermediate- and low-risk prostate cancer should be assessed for TE risk factors before starting ADT and counseled regarding the risks and benefits of this therapy. PMID- 22072496 TI - Nanoparticle cages for enzyme catalysis in organic media. AB - Encapsulation of enzymes in Pickering emulsions results in a large interfacial area of the enzyme-containing aqueous phase for biocatalysis in organic media. This immobilization technique minimizes enzyme inactivation through stabilizing immiscible liquids by particles, facilitates separation processes, and significantly increases catalytic performance of both stable and vulnerable enzymes. Thus, a broad technical applicability can be envisioned. PMID- 22072497 TI - Detection of Pseudomonas aeruginosa isolates of the international clonal complex 11 carrying the blaPER-1 extended-spectrum beta-lactamase gene in Greece. AB - OBJECTIVES: The extended-spectrum beta-lactamase (ESBL) PER-1 initially disseminated among Pseudomonas aeruginosa strains in Turkey. Despite reports from other European countries, such strains have not been detected in Greece until now. We describe the first bla(PER-1)-positive P. aeruginosa isolates from Greece and their genetic environment. METHODS: From January 2008 to December 2009, 287 consecutive non-duplicate P. aeruginosa isolates with reduced susceptibility or resistance to ceftazidime (MIC >8 mg/L) were screened for ESBL production with a modified boronic acid-based double-disc synergy test. Phenotypically ESBL positive isolates were subjected to agar dilution, PFGE and multilocus sequence typing (MLST). Broad-spectrum bla genes were identified by PCR and sequencing. Plasmid analysis and conjugation experiments were performed. The location of the bla(PER-1) gene was detected by Southern blotting and its genetic environment was characterized using inverse PCR. RESULTS: Five isolates were phenotypically positive for ESBL production, exhibited resistance to cefepime, ceftazidime, aztreonam and meropenem, and carried the bla(PER-1) gene. MLST showed that they belonged to sequence type (ST) 235, which belongs to the international clonal complex 11. Four isolates had the same PFGE pattern. Southern blotting revealed the chromosomal location of the bla(PER-1) gene. Analysis of the bla(PER-1) flanking regions showed identity to transposon Tn1213 downstream and 1406 bp upstream of bla(PER-1). Further upstream, an orfA gene and ISPa12 were identified; both were truncated by the insertion of IS6100. CONCLUSIONS: This study confirmed the presence of PER-1-producing P. aeruginosa strains in Greece. The chromosomal location of bla(PER-1), as part of a truncated transposon, suggests clonal expansion rather than horizontal gene transfer. PMID- 22072499 TI - [Pediatric hyperglycemic hyperosmolar coma diabeticum: diagnostic evaluation and therapeutic concept]. AB - Hyperglycemic hyperosmolar coma diabeticum (HHS) is a rare phenomenon in pediatric patients. It causes major morbidity and significant mortality. It is characterized by the trias of hyperglycemia, hyperosmolality and absent or mild metabolic acidosis. Major complications include cerebral edema and rhabdomyolysis. Evidence based guidelines for HHS in children are lacking. Based on a literature review we discuss treatment options in pediatric HHS und suggest a therapeutic concept. Appropriate treatment consists of adequate fluid administration and a cautious lowering of the serum glucose level. Patients should be treated on an intensive care unit and monitored closely to avoid complications. Low-dose and late insulin administration seems to be favourable. PMID- 22072498 TI - Genome-wide association of an integrated osteoporosis-related phenotype: is there evidence for pleiotropic genes? AB - Multiple musculoskeletal traits assessed by various methods at different skeletal sites serve as surrogates for osteoporosis risk. However, it is a challenge to select the most relevant phenotypes for genetic study of fractures. Principal component analyses (PCA) were conducted in participants of the Framingham Osteoporosis Study on 17 measures including bond mineral density (BMD) (hip and spine), heel ultrasound, leg lean mass (LLM), and hip geometric indices, adjusting for covariates (age, height, body mass index [BMI]), in a combined sample of 1180 men and 1758 women, as well as in each sex. Four principal components (PCs) jointly explained ~69% of the total variability of musculoskeletal traits. PC1, explaining ~33% of the total variance, was referred to as the component of "Bone strength," because it included the hip and spine BMD as well as several hip cross-sectional properties. PC2 (20.5% variance) was labeled as "Femoral cross-sectional geometry;" PC3 (~8% variance) captured only ultrasound measures; PC4, explaining ~7% variance, was correlated with LLM and hip geometry. We then evaluated ~2.5 mil SNPs for association with PCs 1, 2, and 4. There were genome-wide significant associations (p < 5 * 10-8) between PC2 and HTR1E (that codes for one of the serotonin receptors) and PC4 with COL4A2 in women. In the sexes-combined sample, AKAP6 was associated with PC2 (p = 1.40 * 10 7). A single nucleotide polymorphism (SNP) in HTR1E was also associated with the risk of nonvertebral fractures in women (p = 0.005). Functions of top associated genes were enriched for the skeletal and muscular system development (p < 0.05). In conclusion, multivariate combination provides genetic associations not identified in the analysis of primary phenotypes. Genome-wide screening for the linear combinations of multiple osteoporosis-related phenotypes suggests that there are variants with potentially pleiotropic effects in established and novel pathways to be followed up to provide further evidence of their functions. PMID- 22072500 TI - Unsteady electroosmosis in a microchannel with Poisson-Boltzmann charge distribution. AB - The present study is concerned with unsteady electroosmotic flow (EOF) in a microchannel with the electric charge distribution described by the Poisson Boltzmann (PB) equation. The nonlinear PB equation is solved by a systematic perturbation with respect to the parameter lambda which measures the strength of the wall zeta potential relative to the thermal potential. In the small lambda limits (lambda<<1), we recover the linearized PB equation - the Debye-Huckel approximation. The solutions obtained by using only three terms in the perturbation series are shown to be accurate with errors <1% for lambda up to 2. The accurate solution to the PB equation is then used to solve the electrokinetic fluid transport equation for two types of unsteady flow: transient flow driven by a suddenly applied voltage and oscillatory flow driven by a time-harmonic voltage. The solution for the transient flow has important implications on EOF as an effective means for transporting electrolytes in microchannels with various electrokinetic widths. On the other hand, the solution for the oscillatory flow is shown to have important physical implications on EOF in mixing electrolytes in terms of the amplitude and phase of the resulting time-harmonic EOF rate, which depends on the applied frequency and the electrokinetic width of the microchannel as well as on the parameter lambda. PMID- 22072501 TI - Expression profiles of carcinosarcoma of the uterine corpus-are these similar to carcinoma or sarcoma? AB - Uterine carcinosarcoma (CS) is usually classified as uterine endometrial carcinoma (EC). However, CS is more aggressive even compared with high grade EC. CS is also reported to undergo epithelial to mesenchymal transition (EMT). In this study, we compared the gene expression profiles of CS, EC, and uterine sarcoma (US) and evaluated the role of EMT and chromosomal aberrations in CS tumor formation. Frozen tissues of 46 patients (14 CS, 24 EC, and 8 US) were included. The similarity was examined by Gene Set Enrichment Analysis (GSEA), Fisher's exact test, and clustering using "intrinsic gene set". We examined the expression of 39 EMT-related genes and evaluated TGF-beta signaling by phospho SMAD2/3 (p-SMAD2/3) staining. Chromosomal regions differing between CS and EC were identified by chromosomal GSEA and comparative genomic hybridization (CGH) microarrays. Three statistical methods confirmed that CS resembled US rather than EC. Acquired markers of EMT were upregulated and attenuated markers of EMT were downregulated in CS. Immunohistochemistry showed that carcinomatous region of CS have higher expression of p-SMAD2/3 than EC (P = 0.008). Chromosomal GSEA showed that genes located at 19q13 had higher expression in CS. Furthermore, CGH microarray indicated that the TGFB1 locus at 19q13.1 was amplified in 4 of 7 samples. Based on the expression profile, CS resembles US rather than EC. TGF beta signaling is activated in CS and chromosomal gains at 19q13, which includes the TGFB1 locus, suggest that this may contribute to high expression of TGF-beta and thereby EMT phenotype of CS. PMID- 22072502 TI - Salvage therapy with endostatin, low-dose homoharringtonine, and cytarabine in combination with granulocyte-colony stimulating factor for elderly patients with primary refractory acute myeloid leukemia. PMID- 22072503 TI - In vitro and in vivo characterization of a novel Hedgehog signaling antagonist in human glioblastoma cell lines. AB - Glioblastoma multiforme (GBM) is composed of heterogeneous and genetically different cells, which are highly invasive and motile. The standard chemotherapeutic agent, temozolomide, affects GBM cell proliferation but is generally unable to prevent tumor recurrence. Hedgehog pathway activation has been reported to be relevant in GBM and different pharmacological pathway modulators have been identified. We report that by growing a commercially available recurrent GBM cell line (DBTRG-05MG) without serum and in the presence of defined growth factors; we obtained a less differentiated cell population, growing in suspension as neurospheres, in which the Hedgehog pathway is activated. Furthermore, the expression profile of Hedgehog pathway components found in DBTRG-05MG neurospheres is similar to primary stem-like cells derived from recurrent GBM patients. We report the effect of our novel specific Smoothened receptor antagonist (SEN450) on neurosphere growing cells and compared its effect to that of well known benchmark compounds. Finally, we showed that SEN450 is both antiproliferative on its own and further reduces tumor volume after temozolomide pretreatment in a mouse xenograft model using DBTRG-05MG neurosphere cells. Altogether our data indicate that the Hedgehog pathway is not irreversibly switched off in adherent cells but can be reactivated when exposed to well-defined culture conditions, thus restoring the condition observed in primary tumor-derived material, and that pharmacological modulation of this pathway can have profound influences on tumor proliferation. Therefore, pharmacological inhibition of the Hedgehog pathway is a potentially useful therapeutic approach in GBM. PMID- 22072504 TI - Androgen deprivation for prostate cancer: the case for "first, do no harm". PMID- 22072505 TI - Glutamate transporter dysfunction associated with nerve injury-induced pain in mice. AB - Dysfunction at glutamatergic synapses has been proposed as a mechanism in the development of neuropathic pain. Here we sought to determine whether peripheral nerve injury-induced neuropathic pain results in functional changes to primary afferent synapses. Signs of neuropathic pain as well as an induction of glial fibrillary acidic protein in immunostained spinal cord sections 4 days after partial ligation of the sciatic nerve indicated the induction of neuropathic pain. We found that following nerve injury, no discernable change to kinetics of dl-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) or N-methyl-d aspartate receptor (NMDAR)-mediated evoked excitatory postsynaptic currents (eEPSCs) could be observed in dorsal horn (lamina I/II) neurons compared with those of naive mice. However, we did find that nerve injury was accompanied by slowed decay of the early phase of eEPSCs in the presence of glutamate transporter inhibition by the competitive nontransportable inhibitor dl-threo beta-benzyloxyaspartic acid (TBOA). Concomitantly, expression patterns for the two major glutamate transporters in the spinal cord, excitatory amino acid transporters (EAAT) 1 and EAAT2, were found to be reduced at this time (4 days postinjury). We then sought to directly determine whether nerve injury results in glutamate spillover to NMDARs at dorsal horn synapses. By employing the use dependent NMDAR blocker (+/-)MK-801 to block subsynaptic receptors, we found that although TBOA-induced spillover to extrasynaptic receptors trended to increased activation of these receptors after nerve injury, this was not significant compared with naive mice. Together, these results suggest the development of neuropathic pain involves subtle changes to glutamate transporter expression and function that could contribute to neuropathic pain during excessive synaptic activity. PMID- 22072506 TI - Single-neuron recordings from unanesthetized mouse dorsal cochlear nucleus. AB - Because of the availability of disease and genetic models, the mouse has become a valuable species for auditory neuroscience that will facilitate long-term goals of understanding neuronal mechanisms underlying the perception and processing of sounds. The goal of this study was to define the basic sound-evoked response properties of single neurons in the mouse dorsal cochlear nucleus (DCN). Neurons producing complex spikes were distinguished as cartwheel cells (CWCs), and other neurons were classified according to the response map scheme previously developed in DCN. Similar to observations in other rodent species, neurons of the mouse DCN exhibit relatively little sound-driven inhibition. As a result, type III was the most commonly observed response. Our findings are generally consistent with the model of DCN function that has been developed in the cat and the gerbil, suggesting that this in vivo mouse preparation will be a useful tool for future studies of auditory physiology. PMID- 22072508 TI - Neural mechanisms of intermuscular coherence: implications for the rectification of surface electromyography. AB - Oscillatory activity plays a crucial role in corticospinal control of muscle synergies and is widely investigated using corticospinal and intermuscular synchronization. However, the neurophysiological mechanisms that translate these rhythmic patterns into surface electromyography (EMG) are not well understood. This is underscored by the ongoing debate on the rectification of surface EMG before spectral analysis. Whereas empirical studies commonly rectify surface EMG, computational approaches have argued against it. In the present study, we employ a computational model to investigate the role of the motor unit action potential (MAUP) on the translation of oscillatory activity. That is, diverse MUAP shapes may distort the transfer of common input into surface EMG. We test this in a computational model consisting of two motor unit pools receiving common input and compare it to empirical results of intermuscular coherence between bilateral leg muscles. The shape of the MUAP was parametrically varied, and power and coherence spectra were investigated with and without rectification. The model shows that the effect of EMG rectification depends on the uniformity of MUAP shapes. When output spikes of different motor units are convolved with identical MUAPs, oscillatory input is evident in both rectified and nonrectified EMG. In contrast, a heterogeneous MAUP distribution distorts common input and oscillatory components are only manifest as periodic amplitude modulations, i.e., in rectified EMG. The experimental data showed that intermuscular coherence was mainly discernable in rectified EMG, hence providing empirical support for a heterogeneous distribution of MUAPs. These findings implicate that the shape of MUAPs is an essential parameter to reconcile experimental and computational approaches. PMID- 22072507 TI - Mitochondria-derived superoxide and voltage-gated sodium channels in baroreceptor neurons from chronic heart-failure rats. AB - Our previous study has shown that chronic heart failure (CHF) reduces expression and activation of voltage-gated sodium (Na(v)) channels in baroreceptor neurons, which are involved in the blunted baroreceptor neuron excitability and contribute to the impairment of baroreflex in the CHF state. The present study examined the role of mitochondria-derived superoxide in the reduced Na(v) channel function in coronary artery ligation-induced CHF rats. CHF decreased the protein expression and activity of mitochondrial complex enzymes and manganese SOD (MnSOD) and elevated the mitochondria-derived superoxide level in the nodose neurons compared with those in sham nodose neurons. Adenoviral MnSOD (Ad.MnSOD) gene transfection (50 multiplicity of infection) into the nodose neurons normalized the MnSOD expression and reduced the elevation of mitochondrial superoxide in the nodose neurons from CHF rats. Ad.MnSOD also partially reversed the reduced protein expression and current density of the Na(v) channels and the suppressed cell excitability (the number of action potential and the current threshold for inducing action potential) in aortic baroreceptor neurons from CHF rats. Data from the present study indicate that mitochondrial dysfunction, including decreased protein expression and activity of mitochondrial complex enzymes and MnSOD and elevated mitochondria-derived superoxide, contributes to the reduced Na(v) channel activation and cell excitability in the aortic baroreceptor neurons in CHF rats. PMID- 22072509 TI - Parameterization of transcranial magnetic stimulation. AB - A recent study (Di Lazzaro et al. J Neurophysiol 105: 2150-2156, 2011) describes the findings from a rigorous comparison on the effects of several popular variations of transcranial magnetic stimulation (TMS) protocols. The results demonstrate that excitatory and inhibitory neural networks may be independently modulated based on TMS protocol selection. Moreover, the within-group replication of multiple between-group experiments suggests that independent evaluations of TMS parameters will continue to inform and guide future TMS research. PMID- 22072511 TI - Spiking and LFP activity in PRR during symbolically instructed reaches. AB - The spiking activity in the parietal reach region (PRR) represents the spatial goal of an impending reach when the reach is directed toward or away from a visual object. The local field potentials (LFPs) in this region also represent the reach goal when the reach is directed to a visual object. Thus PRR is a candidate area for reading out a patient's intended reach goals for neural prosthetic applications. For natural behaviors, reach goals are not always based on the location of a visual object, e.g., playing the piano following sheet music or moving following verbal directions. So far it has not been directly tested whether and how PRR represents reach goals in such cognitive, nonlocational conditions, and knowing the encoding properties in various task conditions would help in designing a reach goal decoder for prosthetic applications. To address this issue, we examined the macaque PRR under two reach conditions: reach goal determined by the stimulus location (direct) or shape (symbolic). For the same goal, the spiking activity near reach onset was indistinguishable between the two tasks, and thus a reach goal decoder trained with spiking activity in one task performed perfectly in the other. In contrast, the LFP activity at 20-40 Hz showed small but significantly enhanced reach goal tuning in the symbolic task, but its spatial preference remained the same. Consequently, a decoder trained with LFP activity performed worse in the other task than in the same task. These results suggest that LFP decoders in PRR should take into account the task context (e.g., locational vs. nonlocational) to be accurate, while spike decoders can robustly provide reach goal information regardless of the task context in various prosthetic applications. PMID- 22072510 TI - A critical window of CAG repeat-length correlates with phenotype severity in the R6/2 mouse model of Huntington's disease. AB - The R6/2 mouse is the most frequently used model for experimental and preclinical drug trials in Huntington's disease (HD). When the R6/2 mouse was first developed, it carried exon 1 of the huntingtin gene with ~150 cytosine-adenine guanine (CAG) repeats. The model presented with a rapid and aggressive phenotype that shared many features with the human condition and was particularly similar to juvenile HD. However, instability in the CAG repeat length due to different breeding practices has led to both decreases and increases in average CAG repeat lengths among colonies. Given the inverse relationship in human HD between CAG repeat length and age at onset and to a degree, the direct relationship with severity of disease, we have investigated the effect of altered CAG repeat length. Four lines, carrying ~110, ~160, ~210, and ~310 CAG repeats, were examined using a battery of tests designed to assess the basic R6/2 phenotype. These included electrophysiological properties of striatal medium-sized spiny neurons, motor activity, inclusion formation, and protein expression. The results showed an unpredicted, inverted "U-shaped" relationship between CAG repeat length and phenotype; increasing the CAG repeat length from 110 to 160 exacerbated the R6/2 phenotype, whereas further increases to 210 and 310 CAG repeats greatly ameliorated the phenotype. These findings demonstrate that the expected relationship between CAG repeat length and disease severity observed in humans is lost in the R6/2 mouse model and highlight the importance of CAG repeat-length determination in preclinical drug trials that use this model. PMID- 22072512 TI - Frequency dependence of vestibuloocular reflex thresholds. AB - How the brain processes signals in the presence of noise impacts much of behavioral neuroscience. Thresholds provide one way to assay noise. While perceptual thresholds have been widely investigated, vestibuloocular reflex (VOR) thresholds have seldom been studied and VOR threshold dynamics have never, to our knowledge, been reported. Therefore, we assessed VOR thresholds as a function of frequency. Specifically, we measured horizontal VOR thresholds evoked by yaw rotation in rhesus monkeys, using standard signal detection approaches like those used in earlier human vestibular perceptual threshold studies. We measured VOR thresholds ranging between 0.21 and 0.76 degrees /s; the VOR thresholds increased slightly with frequency across the measured frequency range (0.2-3 Hz). These results do not mimic the frequency response of human perceptual thresholds that have been shown to increase substantially as frequency decreases below 0.5 Hz. These reported VOR threshold findings could indicate a qualitative difference between vestibular responses of humans and nonhuman primates, but a more likely explanation is an additional dynamic neural mechanism that does not influence the VOR but, rather, influences perceptual thresholds via a decision-making process included in direction recognition tasks. PMID- 22072513 TI - TRPC1 contributes to light-touch sensation and mechanical responses in low threshold cutaneous sensory neurons. AB - The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. However, its role in the mechanical sensitivity of these neurons is unclear. Here, we investigated TRPC1 dependent responses to both innocuous and noxious mechanical force. Mechanically evoked action potentials in cutaneous myelinated A-fiber and unmyelinated C-fiber neurons were quantified using the ex vivo skin-nerve preparation to record from the saphenous nerve, which terminates in the dorsal hairy skin of the hindpaw. Our data reveal that in TRPC1-deficient mice, mechanically evoked action potentials were decreased by nearly 50% in slowly adapting Abeta-fibers, which largely innervate Merkel cells, and in rapidly adapting Adelta-Down-hair afferent fibers compared with wild-type controls. In contrast, differences were not found in slowly adapting Adelta-mechanoreceptors or unmyelinated C-fibers, which primarily respond to nociceptive stimuli. These results suggest that TRPC1 may be important in the detection of innocuous mechanical force. We concurrently investigated the role of TRPC1 in behavioral responses to mechanical force to the plantar hindpaw skin. For innocuous stimuli, we developed a novel light stroke assay using a "puffed out" cotton swab. Additionally, we used repeated light, presumably innocuous punctate stimuli with a low threshold von Frey filament (0.68 mN). In agreement with our electrophysiological data in light-touch afferents, TRPC1-deficient mice exhibited nearly a 50% decrease in behavioral responses to both the light-stroke and light punctate mechanical assays when compared with wild-type controls. In contrast, TRPC1-deficient mice exhibited normal paw withdrawal response to more intense mechanical stimuli that are typically considered measures of nociceptive behavior. PMID- 22072514 TI - Task-dependent coordination of rapid bimanual motor responses. AB - Optimal feedback control postulates that feedback responses depend on the task relevance of any perturbations. We test this prediction in a bimanual task, conceptually similar to balancing a laden tray, in which each hand could be perturbed up or down. Single-limb mechanical perturbations produced long-latency reflex responses ("rapid motor responses") in the contralateral limb of appropriate direction and magnitude to maintain the tray horizontal. During bimanual perturbations, rapid motor responses modulated appropriately depending on the extent to which perturbations affected tray orientation. Specifically, despite receiving the same mechanical perturbation causing muscle stretch, the strongest responses were produced when the contralateral arm was perturbed in the opposite direction (large tray tilt) rather than in the same direction or not perturbed at all. Rapid responses from shortening extensors depended on a nonlinear summation of the sensory information from the arms, with the response to a bimanual same-direction perturbation (orientation maintained) being less than the sum of the component unimanual perturbations (task relevant). We conclude that task-dependent tuning of reflexes can be modulated online within a single trial based on a complex interaction across the arms. PMID- 22072515 TI - Impact of cortical plasticity on patterns of suprathreshold activity in the cerebral cortex. AB - There are many cellular and synaptic mechanisms of plasticity in the vertebrate cortex. How the patterns of suprathreshold spiking activity in a population of neurons change because of this plasticity, however, has hardly been subjected to experimental studies. Here, we measured how evoked patterns of suprathreshold spiking activity in a cortical network were modified by cortical plasticity with single-cell and single-spike resolution. To record patterns of activity in the rodent barrel cortex, we used optical methods to detect suprathreshold activity from up to 40 neurons simultaneously. Pairing of two inputs resulted in a long lasting modification of the cortical responses evoked by one of the inputs. The results indicate that plasticity rules on the network level inherit properties from synaptic plasticity rules but are also determined by the functional synaptic architecture, as well as the computations carried out in cortical networks. The largest determinants of the modified cortical responses were those observed when inducing changes by pairing the two inputs. On the single-neuron level, the modified responses only weakly reflected those observed when pairing the two inputs for induction of plasticity. Despite the weak reflection on the cellular level, however, the modified patterns reflected the pairing patterns to the degree that a simple decoding mechanism-a linear separator-correctly discriminated the modified responses from other patterns of activity. PMID- 22072516 TI - A new synthesis of triarylsilylium ions and their application in dihydrogen activation. AB - Well-shuffled: An unexpected substituent distribution reaction via alkyldiarylsilylium ions leads to a distribution of substituents. Starting from alkyldiaryl silanes, this reaction provides a facile synthetic approach to sterically highly hindered triarylsilylium ions. These silylium ions can be applied in dihydrogen activation reactions. PMID- 22072517 TI - Blind, one-eyed, or eagle-eyed? pKa calculations during blind predictions with staphylococcal nuclease. AB - In the current contribution, the performance of Poisson-Boltzmann-based pK(a) calculations of SNase mutants as part of a blind prediction exercise facilitated by the pK(a) cooperative ("pK(a) _coop") is described. A one parameter setting ("quick&dirty" approach) is used to provide an industry perspective where strong time constraints are frequently encountered. On the one hand, results are analyzed in terms of root mean square deviation performance. Furthermore, the pK(a) calculations are assessed for their ability to properly assign protonation state. For this purpose, a new measure called BIPS (binary protonation state at physiological pH) is introduced. Significant differences were found with both comparison measures based on the class of residues examined. In addition, the performance of PROPKA3 as well as the NULL model is examined on the same data set. Finally, pK(a) calculations on SNase mutants with available structural information have been performed and provide support for our calculation methods. The performance on this subset is better than on the pK(a) cooperative mutation data. In the pK(a) _coop data, no structural information on the generated mutants is available. This suggests the occurrence of a substantial structural rearrangement on the insertion of additional charged groups into SNase, which leads to improved prediction quality. PMID- 22072518 TI - Protein electrostatics and pKa blind predictions; contribution from empirical predictions of internal ionizable residues. AB - In this study, we validate and probe the description of electrostatic interactions within proteins by predicting and comparing pK(a) values of ionizable groups in a series of mutated staphylococcal nuclease variants with experiments. This set of pK(a) values is found to be the most challenging pK(a) data to date, because ionizable residues have been introduced in hydrophobic patches in the protein interior and are therefore significantly shifted from their reference solvated values. We find that using PROPKA2 (Li et al., Proteins 2005;61:704-721) results in an rmsd value close to 2 for true blind predictions (1.6 if we reassign the tightly coupled Asp19/21 pair) and close to 1 for postpredictions with the newly developed PROPKA3 (Olsson et al., J. Chem. Theor. Comp. 2011;7:525-537). We also use the performance of the Null-model, predictions made with the reference value only, to provide a better description of the expected errors in pK(a) predictions and to compare submissions made using different subsets of the pK(a) data more consistently. PMID- 22072519 TI - Exploring conformational changes coupled to ionization states using a hybrid Rosetta-MCCE protocol. AB - A hybrid protocol combining Rosetta fullatom refinement and Multi-Conformation Continuum Electrostatics (MCCE) to estimate pK(a) is applied to the blind prediction of 94 mutated residues in Staphylococcal nuclease (SNase), as part of the pK(a)-cooperative benchmark test. The standard MCCE method is limited to sidechain conformational changes. The Rosetta refinement protocol is used to add the backbone conformational changes in pK(a) calculations. The non-electrostatic energy component from Rosetta and the electrostatic energy from MCCE are combined to weight the calculated ionization states. Of 63 measured pK(a)s, the root mean squared deviation (RMSD) between the calculated pK(a)s and the measured values is 4.3, showing an improvement compared to the RMSD of 6.6 in the standard MCCE calculations, using a low protein dielectric constant of 4. The breakdown of pK(a) shift from the solution values (DeltapK(a)) shows that the desolvation energy contributes the most in the standard MCCE calculations. Lowering desolvation penalties and optimizing electrostatic interactions with the Rosetta/MCCE protocol reduces the DeltapK(a) to favor the charged states. Analysis also showed that the Rosetta/MCCE protocol samples conformations with pK(a)s close to the solution values. The question remains whether the correct conformational changes coupled to the ionization changes are found here. Nevertheless, a challenge emerges to accurately estimate the reorganization energy, which is not directly measured from the electrostatic environment of the site of interest. Possible improvements to the protocol are also discussed. PMID- 22072520 TI - Measuring the successes and deficiencies of constant pH molecular dynamics: a blind prediction study. AB - A constant pH molecular dynamics method has been used in the blind prediction of pK(a) values of titratable residues in wild type and mutated structures of the Staphylococcal nuclease (SNase) protein. The predicted values have been subsequently compared to experimental values provided by the laboratory of Garcia Moreno. CpHMD performs well in predicting the pK(a) of solvent-exposed residues. For residues in the protein interior, the CpHMD method encounters some difficulties in reaching convergence and predicting the pK(a) values for residues having strong interactions with neighboring residues. These results show the need to accurately and sufficiently sample conformational space in order to obtain pK(a) values consistent with experimental results. PMID- 22072521 TI - Histidine in continuum electrostatics protonation state calculations. AB - A modification to the standard continuum electrostatics approach to calculate protein pK(a)s, which allows for the decoupling of histidine tautomers within a two-state model, is presented. Histidine with four intrinsically coupled protonation states cannot be easily incorporated into a two-state formalism, because the interaction between the two protonatable sites of the imidazole ring is not purely electrostatic. The presented treatment, based on a single approximation of the interrelation between histidine's charge states, allows for a natural separation of the two protonatable sites associated with the imidazole ring as well as the inclusion of all protonation states within the calculation. PMID- 22072522 TI - Is the prediction of pKa values by constant-pH molecular dynamics being hindered by inherited problems? AB - In this study, we investigate two factors that can hinder the performance of constant-pH molecular dynamics methods in predicting protein pK(a) values, using hen egg white lysozyme as a test system. The first factor is related to the molecular definition and pK(a) value of model compounds in the Poisson-Boltzmann framework. We address this by defining the model compound as a molecular fragment with an associated pK(a) value that is calibrated against experimental data, which results in a decrease of 0.12 units in pK(a) errors. The second addressed factor is the possibility that detrimental structural distortions are being introduced in the simulations by the underlying molecular mechanics force field. This issue is investigated by analyzing how the gradual structural rearrangements affect the predicted pK(a) values. The two GROMOS force fields studied here (43A1 and 53A6) yield good pK(a) predictions, although a time-dependent performance is observed: 43A1 performs better after a few nanoseconds of structural reorganization (pK(a) errors of ~0.45), while 53A6 gives the best prediction right at the first nanosecond (pK(a) errors of 0.42). These results suggest that the good performance of constant-pH molecular dynamics methods could be further improved if these force field limitations were overcome. PMID- 22072523 TI - Energetics of charge-charge interactions between residues adjacent in sequence. AB - Statistical analysis of the residue separation between a pair of ionizable side chains within 4 A of each other was performed on a set of 1560 non-homologous PDB structures. We found that the frequency of pairs of like charges (i.e., pairs consisting of acidic residues Asp and Glu or pairs consisting of basic residues Arg and Lys) is two orders of magnitude lower than the pairs of oppositely charged residues (salt-bridges). We also found that for pairs of like charges the distribution is skewed dramatically towards short residue separation (<3). On the basis of these observations, we hypothesize that at short residue separation the repulsion between charges does not contribute much to the protein stability and the effects are largely dominated by the long range charge-charge interactions with other ionizable groups in the protein molecule. To test this hypothesis, we incorporated various pairs of charged residues at position 63 and 64 of ubiquitin and compared the stabilities of these variants. We also performed calculations of the expected changes in the charge-charge interactions. A very good correlation between experimental changes in the stability of ubiquitin variants, and changes in the energy of charge-charge interactions provides support for the hypothesis that a pair of ionizable residues next to each other in sequence modulates protein stability via long range charge-charge interactions with the rest of the protein. PMID- 22072524 TI - Photodynamic therapy of Pheophorbide a inhibits the proliferation of human breast tumour via both caspase-dependent and -independent apoptotic pathways in in vitro and in vivo models. AB - Breast cancer is conventionally treated by surgery and radiotherapy, with adjuvant chemotherapy and hormonotherapy as supplementary treatments. However, such treatments are associated with adverse side effects and drug resistance. In this study, Pheophorbide a (Pa), a photosensitizer isolated from Scutelleria barbata, was analysed for its antiproliferative effect on human breast tumour cells. The IC (inhibitory concentration)(50) of the combined treatment of Pa and photodynamic therapy (Pa-PDT) on human breast tumour MCF-7 cells was 0.5 um. Mechanistic studies in MCF-7 cells demonstrated that Pa was localized in the mitochondria, and reactive oxygen species were found to be released after Pa-PDT. Apoptosis was the major mechanism responsible for the tumour cell death, and mitochondrial membrane depolarization and cytochrome c release highlighted the role of mitochondria in the apoptotic mechanism. Up-regulation of tumour suppressor protein p53, cleavage of caspase-9 and poly (ADP-ribose) polymerase suggested that the caspase-dependent pathway was induced, while the release of apoptosis-inducing factors demonstrated that the apoptosis was also mediated by the caspase-independent mechanism. In vivo study using the mouse xenograft model showed a significant inhibition of MCF-7 tumour growth by Pa-PDT. Together, the results of this study provide a basis for understanding and developing Pa-PDT as a cure for breast cancer. PMID- 22072525 TI - A simple elastic membrane-based microfluidic chip for the proliferation and differentiation of mesenchymal stem cells under tensile stress. AB - This work presents a simple membrane-based microfluidic chip for the investigation of proliferation and differentiation of mesenchymal stem cells (MSCs) under mechanical stimuli. The cyclic tensile stress was generated by the deformation of elastic PDMS membrane sandwiched between the two layer microfluidic chip via actuated negative pressure, and the cultured MSCs on membrane were subjected to different orders of tensile stress. The results suggest that mechanical stimuli are attributed to the different phenomena of MSCs in cell proliferation and differentiation. The higher tensile stress (>3.5) promoted obvious proliferation, osteogenesis and reduced adipogenesis in MSCs, indicating the possible regulative role of tensile stress in modifying the osteogenesis/adipogenesis balance in the development of tissue organ. PMID- 22072526 TI - Casitas B lymphoma mutations in childhood acute lymphoblastic leukemia. AB - Casitas B-lineage lymphoma (CBL) proteins are RING finger ubiquitin E3 ligases that attenuate the signaling of receptor tyrosine kinases and are mutated in a number of myeloid disorders. In this study, mutational screening of the linker RING domains of CBL and CBLB was performed by denaturing high performance liquid chromatography in a cohort of diagnostic (n = 180) or relapse (n = 46) samples from children with acute lymphoblastic leukemia. Somatic mutations were identified in three children, giving an overall incidence of 1.7% and involved small deletions affecting the intron/exon boundaries of exon 8, leading to skipping of exon 8 and abolishing E3 ligase function. Mutated primary samples were associated with constitutive activation of the RAS pathway and sensitivity to MEK inhibitors was shown. Thus, mutation of CBL is an alternative route to activate the RAS pathway and may identify children who are candidates for MEK inhibitor clinical trials. PMID- 22072527 TI - Toxic erythema of chemotherapy. PMID- 22072528 TI - Struggling and enduring with God, religious support, and recovery from severe mental illness. AB - OBJECTIVES: People with severe mental illnesses may achieve varying degrees of recovery, including symptom reduction and community integration. Research also indicates that religiosity facilitates coping with psychological disorders. In this study, we assessed the relationship between religiosity and recovery from severe mental illnesses. DESIGN: Self-report data were collected from 81 participants with severe mental illnesses. We measured recovery, religious support, and participants' struggle or endurance with faith. RESULTS: Religious support and enduring with faith were positively associated with recovery. Struggling was negatively associated with recovery, and that relationship was mediated by religious support. CONCLUSIONS: Religious variables, including religious support and spiritual struggle, might affect recovery from severe mental illnesses. PMID- 22072529 TI - Recurrence after complete resection and selective use of adjuvant therapy for stage I through III Merkel cell carcinoma. AB - BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm whose natural history is poorly understood. Here, the authors describe their experience with a large cohort of patients who were treated at a single institution to describe patterns of recurrence after curative therapy. METHODS: Review of a prospective database was performed. Patient-related, tumor-related, and treatment-related variables were recorded, and the site and timing of initial recurrence were recorded. Factors associated with receipt of adjuvant therapy and recurrence were determined. RESULTS: In total, 364 patients with stage I through III MCC who underwent complete resection were identified. Adjuvant local radiation therapy (RT), lymph node RT, and chemotherapy were received selectively by 23%, 23%, and 15% of patients, respectively. Factors associated with the receipt of adjuvant therapy included younger age, primary tumor features (larger size, lymphovascular invasion [LVI], positive margin excision), and increasing pathologic stage. With median follow-up of 3.6 years, 108 patients (30%) developed a recurrence, including 11 local recurrences (3%), 12 in-transit recurrences (3%), 43 lymph node recurrences (12%), and 42 distant recurrences (12%). Clinically involved lymph nodes, primary tumor LVI, and a history of leukemia/lymphoma were predictive of recurrence. The majority of recurrences (80%) occurred in patients who had clinically involved lymph nodes or patients who did not undergo pathologic lymph node evaluation. CONCLUSIONS: A low recurrence rate in patients with clinically lymph node-negative MCC was achieved with adequate surgery (including sentinel lymph node biopsy) and the selective use of adjuvant RT for high-risk tumors. In contrast, patients with clinically lymph node-positive MCC had significantly higher rates of recurrence, especially distant recurrence. The authors concluded that contemporary natural history studies are critical in designing treatment pathways and clinical trials for MCC. PMID- 22072530 TI - Tips and tricks to prevent prolapse of the Amplatzer septal occluder through large atrial septal defects. AB - We report on a new technique "using a partially inflated balloon through the atrial septal defect" to prevent prolapse of the left atrial disk of the Amplatzer septal occulder in large atrial septal defects (ASDs). Two patients underwent successful closure of their ASDs using this new technique. PMID- 22072531 TI - SIDEpro: a novel machine learning approach for the fast and accurate prediction of side-chain conformations. AB - Accurate protein side-chain conformation prediction is crucial for protein modeling and existing methods for the task are widely used; however, faster and more accurate methods are still required. Here we present a new machine learning approach to the problem where an energy function for each rotamer in a structure is computed additively over pairs of contacting atoms. A family of 156 neural networks indexed by amino acid and contacting atom types is used to compute these rotamer energies as a function of atomic contact distances. Although direct energy targets are not available for training, the neural networks can still be optimized by converting the energies to probabilities and optimizing these probabilities using Markov Chain Monte Carlo methods. The resulting predictor SIDEpro makes predictions by initially setting the rotamer probabilities for each residue from a backbone-dependent rotamer library, then iteratively updating these probabilities using the trained neural networks. After convergences of the probabilities, the side-chains are set to the highest probability rotamer. Finally, a post processing clash reduction step is applied to the models. SIDEpro represents a significant improvement in speed and a modest, but statistically significant, improvement in accuracy when compared with the state-of-the-art for rapid side-chain prediction method SCWRL4 on the following datasets: (1) 379 protein test set of SCWRL4; (2) 94 proteins from CASP9; (3) a set of seven large protein-only complexes; and (4) a ribosome with and without the RNA. Using the SCWRL4 test set, SIDEpro's accuracy (chi(1) 86.14%, chi(1+2) 74.15%) is slightly better than SCWRL4-FRM (chi(1) 85.43%, chi(1+2) 73.47%) and it is 7.0 times faster. On the same test set SIDEpro is clearly more accurate than SCWRL4-rigid rotamer model (RRM) (chi(1) 84.15%, chi(1+2) 71.24%) and 2.4 times faster. Evaluation on the additional test sets yield similar accuracy results with SIDEpro being slightly more accurate than SCWRL4-flexible rotamer model (FRM) and clearly more accurate than SCWRL4-RRM; however, the gap in CPU time is much more significant when the methods are applied to large protein complexes. SIDEpro is part of the SCRATCH suite of predictors and available from: http://scratch.proteomics.ics.uci.edu/. PMID- 22072532 TI - The role of capillarisin from Artemisia capillaris on penile erection. AB - The objective of this study was to evaluate the effect and mechanism of capillarisin from Artemisia capillaris (A. capillaris) on rabbit penile corpus cavernosum (PCC). The pre-contracted New Zealand White rabbit (2.5-3.0 kg) penis with phenylephrine (Phe; 10-5 M) was treated with various concentrations of ethanol extract of A. capillaris (0.1, 0.5, 1, and 2 mg/mL) and capillarisin, the active component of A. capillaris (10-7, 10-6, 10-5 and 10-4 M). Capillarisin was also applied to PCC tissues contracted with Phe, which were pre-incubated with phosphodiesterase type 5 inhibitors (PDE5 Is). Cyclic nucleotides in the perfusate were measured by radioimmunoassay. The tissues were pre-incubated with Nomega nitro-l-arginine-methyl ester (L-NAME, 10-3 M) and 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10-5 M) to block nitric oxide (NO) synthase and guanylate cyclase, respectively. Capillarisin induced penile relaxation and enhanced PDE5 Is-induced relaxation. Capillarisin increased cGMP and cAMP in the perfusate. The application of capillarisin on PCC pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Capillarisin exerts the relaxing effect on PCC by activating the NO-cGMP and adenylyl cAMP signaling pathways and may become an alternative medicine for patients who want to use natural products to improve erectile function or do not completely respond to PDE5 Is. PMID- 22072533 TI - A SERS-active microfluidic device with tunable surface plasmon resonances. AB - A surface-enhanced Raman scattering (SERS)-active microfluidic device with tunable surface plasmon resonances is presented here. It is constructed by silver grating substrates prepared by two-beam laser interference of photoresists and subsequent metal evaporation coating, as well as PDMS microchannel derived from soft lithography. By varying the period of gratings from 200 to 550 nm, surface plasmon resonances (SPRs) from the metal gratings could be tuned in a certain range. When the SPRs match with the Raman excitation line, the highest enhancement factor of 2*10(7) is achieved in the SERS detection. The SERS-active microchannel with tunable SPRs exhibits both high enhancement factor and reproducibility of SERS signals, and thus holds great promise for applications of on-chip SERS detection. PMID- 22072534 TI - Personalities of adults with traumatic childhood separations. AB - OBJECTIVES: This study examined personality characteristics and identified personality subtypes of adults with childhood histories of traumatic separations from a parent. Previous work from attachment theory and developmental psychopathology suggests that distinct developmental trajectories might lead to different styles of personality adaptation after an attachment disruption. design: Randomly selected psychologists and psychiatrists provided data on 203 adults with histories of traumatic separations using a personality pathology instrument designed for use by clinically experienced observers, the Shedler Westen Assessment Procedure (SWAP-II). RESULTS: Using a Q-factor analysis, 5 distinct personality subtypes were identified: internalizing/avoidant, psychopathic, emotionally dysregulated, hostile/paranoid, and resilient. Initial support for the validity of the subtypes was established, based on Axis I and Axis II pathology, adaptive functioning, developmental history, and family history variables. CONCLUSIONS: Both therapeutic interventions and case formulation might be strengthened by considering an individual's personality features and match to one of the identified subtypes. PMID- 22072535 TI - Fractionated doses of gemtuzumab ozogamicin with escalated doses of daunorubicin and cytarabine as first acute myeloid leukemia salvage in patients aged 50-70 year old: a phase 1/2 study of the acute leukemia French association. AB - This Phase 1/2 study aimed to determine optimal doses of daunorubicin (DNR; mg/m(2)) and cytarabine (mg/m(2)) to be combined with fractionated doses of gemtuzumab ozogamicin (GO, Mylotarg((r)); 3 mg/m(2) on day 1, 4, and 7) satisfying safety requirements. Three dose levels of DNR/AraC were investigated namely (45, 100), (60, 100), and (60, 200). Patients included were acute myeloid leukemia in first relapse, aged 50-70 years. Hematological recovery was 31 days for neutrophil and 32 days for platelet counts. A documented infectious episode > Grade 2 occurred in 11/20 patients (55%). None of the 20 patients had signs of veno-occlusive disease. Overall, eleven patients reached complete remission (CR), two CR with incomplete platelets recovery. The results showed that combination of fractionated GO doses with DNR at 60 mg/m(2)/d for 3 days and cytarabine at 200 mg/m(2)/d for 7 days is tolerable and could be further investigated in the front line therapy. PMID- 22072536 TI - Reasons for underuse of recommended therapies for colorectal and lung cancer in the Veterans Health Administration. AB - BACKGROUND: Many studies have documented low rates of effective cancer therapies, particularly in older or minority populations. However, little is known about why effective therapies are underused in these populations. METHODS: The authors examined medical records of 584 patients with cancer diagnosed or treated in Department of Veterans Affairs facilities to assess reasons for lack of 1) surgery for stage I/II nonsmall cell lung cancer, 2) surgery for stage I/II/III rectal cancer, 3) adjuvant radiation therapy for stage II/III rectal cancer, and 4) adjuvant chemotherapy for stage III colon cancer. They also assessed differences in reasons for underuse by patient age and race. RESULTS: Across the 4 guideline-recommended treatments, 92% to 99% of eligible patients were referred to the appropriate cancer specialist; however, therapy was recommended in only 74% to 92% of eligible cases. Poor health was cited in the medical record as the reason for lack of therapy in 15% to 61% of underuse cases; patient refusal explained 26% to 58% of underuse cases. African American patients were more likely to refuse surgery. Older patients were more likely to refuse treatments. CONCLUSIONS: Recommendation against therapy was a primary factor in underuse of effective therapies in older and sicker patients. Patients' refusal of therapy contributed to age and racial disparities in care. Improved data on the effectiveness of cancer therapies in community populations and interventions aimed at improved communication of known risks and benefits of therapy to cancer patients could be effective tools to reduce underuse and lingering disparities in care. PMID- 22072537 TI - Validity and variability in visual assessment of stenosis severity in phantom bifurcation lesions: a survey in experts during the fifth meeting of the European Bifurcation Club. AB - OBJECTIVES: To investigate the adequacy of visual estimate regarding the percent diameter stenosis (DS) in bifurcation lesions. BACKGROUND: Quantitative coronary angiography (QCA) is more accurate and precise compared to visual estimate in assessing stenosis severity in single-vessel lesions. METHODS: Thirty-six experts in the field of bifurcation PCI visually assessed the DS in cine images of five precision manufactured phantom bifurcation lesions, experts being blinded to the true values. Expert DS estimates were compared with the true values and they were also used to define the Medina class of each individual bifurcation. Results were pooled together both for proximal main vessel (PMV), distal main vessel (DMV) and side-branch (SB) segments and for vessel segments with similar DS values. RESULTS: Individual performance was highly variable among observers; pooled values and range of accuracy and precision were 2.79% (-6.67% to 17.33%) and 8.69% (4.31-16.25%), respectively. On average, DS was underestimated in the PMV ( 1.08%, P = 0.10) and overestimated in the DMV (3.86% P < 0.01) and SB segments (5.58%, P < 0.01). Variability in visual estimates was significantly larger in lesions of medium severity compared to the clearly obstructive ones (P < 0.01); the latter were consistently overestimated. Inter-observer agreement was moderate (kappa = 0.55) over the entire number of estimates. However, if the segments with true DS = 0% were excluded, agreement was diminished (kappa = 0.27). Inter observer agreement in Medina class was rather low (kappa = 0.21). True bifurcation lesions were misclassified as non-true ones in 14/180 estimates. CONCLUSIONS: Visual assessment by experts is more variable and less precise in the analysis of bifurcation lesions compared to bifurcation QCA software. PMID- 22072538 TI - Solution structure of gp17 from the Siphoviridae bacteriophage SPP1: insights into its role in virion assembly. PMID- 22072539 TI - Molecular targets of the antiinflammatory Harpagophytum procumbens (devil's claw): inhibition of TNFalpha and COX-2 gene expression by preventing activation of AP-1. AB - Harpagophytum procumbens (Hp) is often used in the supportive treatment of inflammatory and degenerative diseases of the skeletal system. Although the clinical efficacy in osteoarthritis has been demonstrated in clinical trials, the molecular target(s) of Hp are unclear. This study quantified the effects of the ethanol Hp extract (60% v/v ethanol, sole active ingredient of Pascoe(r)-Agil), on the expression and release of the major pro-inflammatory mediators in LPS stimulated human monocytes and the intracellular signalling pathways involved in inflammation. The Hp extract dose-dependently inhibited the release of TNFalpha as well as that of interleukin (IL)-6, IL-1beta and prostaglandin E2 (PGE2). The Hp prevented TNFalpha and IL-6 mRNA expression in human monocytes and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. Furthermore, the Hp extract inhibited LPS-stimulated AP-1-mediated gene transcription activity and binding to the AP-1 response elements. The extract had no effect on the LPS-induced binding of nuclear factor-kappaB in RAW 264.7 cells, on LPS-induced degradation of IkappaBalpha or on LPS-induced activation of mitogen-activated protein kinases (MAPK), p38MAPK and JNK in human monocytes. The data indicate that a standardized ethanol Hp extract inhibits induction of pro-inflammatory gene expression, possibly by blocking the AP-1 pathway. This is novel evidence of a possible mechanism of action of this antiinflammatory drug. PMID- 22072540 TI - Gene expression of BAALC, CDKN1B, ERG, and MN1 adds independent prognostic information to cytogenetics and molecular mutations in adult acute myeloid leukemia. AB - Expression of BAALC, ERG, and MN1 is associated with outcome in normal karyotype acute myeloid leukemia (AML). In this study, the expression of these markers and of EVI1 and CDKN1B was determined using oligonucleotide microarrays in 286 AML comprising all cytogenetic groups. Higher expression of each gene was associated with an inferior outcome: CDKN1B, median overall survival (mOS): 14.9 months vs. not reached (nr), P = 0.005, median event-free survival (mEFS): 9.7 vs. 31.0 months, P = 0.013; BAALC, no impact on OS, mEFS: 6.2 vs. 13.0 months, P = 0.03; ERG: mOS: 12.5 months vs. nr, P = 0.002, mEFS: 8.1 vs. 15.7 months, P = 0.001; MN1: mOS: 12.3 months vs. nr, P = 0.004, mEFS: 8.1 vs. 16.7 months, P = 0.001. A multivariate analysis revealed an independent impact on OS for CDKN1B, ERG, and MN1 expression. A novel score based on BAALC, CDKN1B, ERG, and MN1 expression had an impact on OS and EFS independent of cytogenetics and age. A score taking into account gene expression and karyotype allowed the separation of four prognostic groups with significant differences in OS and EFS (OS at 2 years: 90.4%, 56.4%, 34.0%, 12.6%; mEFS: n.r., 18.1 months, 8.7 months, 2.5 months). The impact on outcome of this score was independent of NPM1mut/FLT3-ITD- status, MLL-PTD, and age. PMID- 22072541 TI - A prototypic system of parallel electrophoresis in multiple capillaries coupled with microwell arrays. AB - We present a microfluidic system that can be directly coupled with microwell array and perform parallel electrophoresis in multiple capillaries simultaneously. The system is based on an array of glass capillaries, fixed in a polydimethylsiloxane (PDMS) microfluidic scaffold, with one end open for interfacing with microwells. In this capillary array, every two adjacent capillaries act as a pair to be coupled with one microwell; samples in the microwells are introduced and separated by simply applying voltage between two electrodes that are placed at the other ends of capillaries; thus no complicated circuit design is required. We evaluate the performance of this system and perform multiple CE with direct sample introduction from microwell array. Also with this system, we demonstrate the analysis of cellular contents of cells lysed in a microwell array. Our results show that this prototypic system is a promising platform for high-throughput analysis of samples in microwell arrays. PMID- 22072542 TI - Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. AB - Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was a high rate of IDH mutations: all cases had mutations in either IDH1 (14/16) or IDH2 (2/16). In addition, we discovered somatic mutations and insertions/deletions in the CIC gene on chromosome 19q13.2 in 13/16 tumours. These discovery set mutations were validated by deep sequencing of 13 additional tumours, which revealed seven others with CIC mutations, thus bringing the overall mutation rate in oligodendrogliomas in this study to 20/29 (69%). In contrast, deep sequencing of astrocytomas and oligoastrocytomas without 1p/19q loss revealed that CIC alterations were otherwise rare (1/60; 2%). Of the 21 non-synonymous somatic mutations in 20 CIC-mutant oligodendrogliomas, nine were in exon 5 within an annotated DNA-interacting domain and three were in exon 20 within an annotated protein-interacting domain. The remaining nine were found in other exons and frequently included truncations. CIC mutations were highly associated with oligodendroglioma histology, 1p/19q co-deletion, and IDH1/2 mutation (p < 0.001). Although we observed no differences in the clinical outcomes of CIC mutant versus wild-type tumours, in a background of 1p/19q co-deletion, hemizygous CIC mutations are likely important. We hypothesize that the mutant CIC on the single retained 19q allele is linked to the pathogenesis of oligodendrogliomas with IDH mutation. Our detailed study of genetic aberrations in oligodendroglioma suggests a functional interaction between CIC mutation, IDH1/2 mutation, and 1p/19q co deletion. PMID- 22072543 TI - The Italian Registry of Therapeutic Apheresis: granulocyte-monocyte apheresis in the treatment of inflammatory bowel disease. A multicentric study. AB - Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte-monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n = 194) or Crohn's disease (CD, n = 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn's disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered. PMID- 22072544 TI - Surface-histogram: a new shape descriptor for protein-protein docking. AB - Determining the structure of protein-protein complexes remains a difficult and lengthy process, either by NMR or by X-ray crystallography. Several computational methods based on docking have been developed to support and even serve as possible alternatives to these experimental methods. In this article, we introduce a new protein-protein docking algorithm, shDock, based on shape complementarity. We characterize the local geometry on each protein surface with a new shape descriptor, the surface-histogram. We measure the complementarity between two surface-histograms, one on each protein, using a modified Manhattan distance. When a match is found between two local protein surfaces, a model is generated for the protein complex, which is then scored by checking for collision between the two proteins. We have tested our algorithm on Version 3 of the ZDOCK protein-protein docking benchmark. We found that for 110 out of the 124 test cases of bound docking in the benchmark, our algorithm was able to generate a model in the top 3600 candidates for the protein complex within an root-mean square deviation of 2.5 A from its native structure. For unbound docking predictions, we found a model within 2.5 A in the top 3600 models in 54 out of 124 test cases. A comparison with other shape-based docking algorithms demonstrates that our approach gives significantly improved performance for both bound and unbound docking test cases. PMID- 22072545 TI - Reduction of inflammatory hyperplasia in the intestine in colon cancer-prone mice by water-extract of Cistanche deserticola. AB - Cistanche deserticola has commonly been used in traditional Chinese medicine to treat many health problems including irritable bowel syndrome or constipation. This study was designed to test the efficacy of a water-extract of C. deserticola in the prevention of colorectal cancer in a mouse model. Polysaccharide-rich water-extract of C. deserticola was prepared by boiling its stem powder in distilled water. Tgfb1Rag2 null mice were used as an experimental model. Here we showed that feeding of water-extract of C. deserticola significantly reduced the number of mucosal hyperplasia and intestinal helicobacter infection in mice. This beneficial effect correlated with significant stimulation of the immune system, evidenced by the enlargement of the spleens with increased number of splenic macrophage and natural killer cells, and with more potent cytotoxicity of splenocytes. In vitro water-extract of C. deserticola enhanced the cytotoxicity of naive splenocytes against a human colon cancer cell line, and in macrophage cultures up-regulated nitric oxide synthase II expression and stimulated phagocytosis. In conclusion, our data indicate that oral administration of C. deserticola extract reduces inflammatory hyperplastic polyps and helicobacter infection in mice by its immune-stimulatory activity, suggesting that C. deserticola extract may have potential in preventing intestinal inflammation disorders including colorectal cancer. PMID- 22072546 TI - Associations between variants in KITLG, SPRY4, BAK1, and DMRT1 and pediatric germ cell tumors. AB - Recent genome wide association studies have identified susceptibility loci for adult testicular germ cell tumors (GCT) near KITLG, SPRY4, BAK1, and DMRT1. We evaluated variants in these four genes to determine whether these are also susceptibility loci for pediatric GCTs. DNA was isolated from 52 pediatric GCTs (ages 0-21 years) obtained from the Cooperative Human Tissue Network. Control DNA was isolated from de-identified dried blood spots from 141 white newborns. Genotyping was conducted using TaqMan assays (rs4474514) or by PCR and sequencing (rs4324715, rs210138, and rs755383). Associations between variants and GCT were evaluated using logistic regression with adjustment for sex. We also evaluated whether the associations differed by age at GCT diagnosis (0-9 years, 10-21 years), sex, and tumor location (gonadal, non-gonadal). We observed a significant association for rs210138 (BAK1) and pediatric GCT overall (odds ratio (OR) = 1.80, 95% confidence interval (CI) 1.10-2.95, P = 0.02) with non-significant associations similar in magnitude in both the pediatric (P = 0.09) and adolescent (P = 0.06) age groups. The KITLG (rs4474514) and SPRY4 (rs4324715) variants were significantly associated with GCT only in the adolescent age group (rs4474514: OR = 2.28, 95% CI 1.09-4.79, P = 0.03 and rs4324715: OR = 2.40, 95% CI 1.19-4.83, P = 0.01). Associations were mostly similar when stratified by sex. This is the first study to suggest that these loci may also be important in susceptibility to GCTs in the adolescent (KITLG, SPRY4, and BAK1) and pediatric (BAK1) age groups. PMID- 22072547 TI - A simultaneous space sampling method for DNA fraction collection using a comb structure in microfluidic devices. AB - Fraction collection of selected components from a complex mixture plays a critical role in biomedical research, environmental analysis, and biotechnology. Here, we introduce a novel electrophoretic chip device based on a signal processing theorem that allows simultaneous space sampling for fractionation of ssDNA target fragments. Ten parallel extraction channels, which covered 1.5-mm long sampling ranges, were used to facilitate the capturing of fast-moving fragments. Furthermore, the space sampling extraction made it possible to acquire pure collection, even from partly overlapping fragments that had been insufficiently separated after a short electrophoretic run. Fragments of 180, 181, and 182 bases were simultaneously collected, and then the recovered DNA was PCR amplified and assessed by CE analysis. The 181-base target was shown to be isolated in a 70-mm-long separation length within 10 min, in contrast to the >50 min required for the 300-mm-long separation channel in our previous study. This method provides effective combination of time and space, which is a breakthrough in the traditional concept of fraction collection on a chip. PMID- 22072548 TI - Lenograstim with or without dexamethasone for neutrophil mobilization in healthy donors: short-term kinetics of white blood cells and effects of granulocyte apheresis. AB - OBJECTIVES: To determine the optimal time schedule for neutrophil collection after single mobilization with glycosylated recombinant granulocyte colony stimulating factor (G-CSF, lenograstim) with or without dexamethasone (DXM). DONORS AND METHODS: In this prospective randomized trial, 26 healthy volunteers were randomly assigned to a single subcutaneous dose of lenograstim 6 MUg/kg plus 8-mg DXM (G-CSF/DXM, n = 13) or placebo (G-CSF/placebo, n = 13). Hematological and biochemical parameters were analyzed before and 12, 15, 18, 21, 24, 27, 29, 36, 48, 60, 72, and 84 h and 7 and 30 days after mobilization. Six G-CSF/DXM subjects underwent standard neutrophil apheresis (NA) 12 and 36 h after mobilization. RESULTS: Polymorphonuclear neutrophil (PMN) counts 12 and 21 h after mobilization were 22.7 (16.6-32.8) * 10(9) /L and 22.4 (18.6-30.6) * 10(9) /L for G-CSF/placebo versus 33.1 (24.2-44.9) * 10(9) /L and 32.5 (17.4-39.6) * 10(9) /L for G-CSF/DXM. This mobilization plateau was followed by slow normalization at 72-84 h. The six NA subjects had median PMN yields of 62 (47 101) * 10(9) and 39 (23-42) * 10(9) per therapeutic unit. After the first apheresis, PMN counts sharply decreased to 21.1 (14.8-26.3) * 10(9) /L and then temporarily recovered to 25.9 (18.9-36.5) * 10(9) /L (P <= 0.001) over the next 8 h. CONCLUSIONS: Single doses of lenograstim with or without DXM induced a PMN plateau that lasted 9 h (12-21 h after mobilization), with PMN counts suitable for neutrophil collection. Lenograstim plus DXM made it possible to perform NA twice, 12 and 36 h after mobilization. PMID- 22072549 TI - On the molecular structure of human neuroserpin polymers. AB - The polymerization of serpins is at the root of a large class of diseases; the molecular structure of serpin polymers has been recently debated. In this work, we study the polymerization kinetics of human neuroserpin by Fourier Transform Infra Red spectroscopy and by time-lapse Size Exclusion Chromatography. First, we show that two distinct neuroserpin polymers, formed at 45 and 85 degrees C, display the same isosbestic points in the Amide I' band, and therefore share common secondary structure features. We also find a concentration independent polymerization rate at 45 degrees C suggesting that the polymerization rate limiting step is the formation of an activated monomeric species. The polymer structures are consistent with a model that predicts the bare insertion of portions of the reactive center loop into the A beta-sheet of neighboring serpin molecule, although with different extents at 45 and 85 degrees C. PMID- 22072550 TI - Frequency-dependent electrophysiological remodeling of the AV node by hydroalcohol extract of Crocus sativus L. (saffron) during experimental atrial fibrillation: the role of endogenous nitric oxide. AB - The study assessed the hydroalcohol extract effects of Crocus sativus L. (saffron) on (i) the basic and rate-dependent electrophysiological properties of the AV node, (ii) remodeling of the AV node during experimental atrial fibrillation (AF) and (iii) the role of nitric oxide (NO) in the effects of saffron on the AV node. Stimulation protocols in isolated AV node were used to quantify AV nodal recovery, facilitation and fatigue in four groups of rabbits (n = 8-16 per group). In addition, the nodal response to AF was evaluated at multiple cycle lengths and during AF. Saffron had a depressant effect on AV nodal rate-dependent properties; further, it increased Wenckebach block cycle length, functional refractory period, facilitation and fatigue (p < 0.05). A NO-synthase inhibitor (L-NAME) prevented the depressant effects of saffron on the AV node (p < 0.05). Saffron increased the zone of concealment in experimental AF (p < 0.05). The present research showed, for the first time, established electrophysiological remodeling of the AV node during AF by saffron. Saffron increased the AV nodal refractoriness and zone of concealment. These depressant effects of saffron were mediated by endogenous NO. PMID- 22072551 TI - Solvent bonding of poly(methyl methacrylate) microfluidic chip using phase changing agar hydrogel as a sacrificial layer. AB - In this report, a solvent bonding method based on phase-changing agar hydrogel has been developed for the fabrication of poly(methyl methacrylate) (PMMA) microfluidic chips. Prior to bonding, the channels and the reservoir ports on PMMA channel plates were filled with molten agar hydrogel that could gelate to form solid sacrificial layers at room temperature. Subsequently, PMMA cover sheets were covered on the channeled plates and 1,2-dichlororethane was applied to the interspaces between them. The agar hydrogel in the channels could prevent the bonding solvent and the softened surface of the PMMA cover sheets from filling in the channels. After solvent bonding, the agar hydrogel in the channels and the reservoir ports was melted and removed under pressure. The sealed channels in the complete microchips had been examined by an optical microscope and a scanning electron microscope. The results indicated that high-quality bonding was achieved at room temperature. The prepared microfluidic microchips have been successfully employed in the electrophoresis separation and detection of three cations in combination with contactless conductivity detection. PMID- 22072552 TI - Requirement of phospholipase C and protein kinase C in cholecystokinin-mediated facilitation of NMDA channel function and anxiety-like behavior. AB - Although cholecystokinin (CCK) has long been known to exert anxiogenic effects in both animal anxiety models and humans, the underlying cellular and molecular mechanisms are ill-defined. CCK interacts with CCK-1 and CCK-2 receptors resulting in up-regulation of phospholipase C (PLC) and protein kinase C (PKC). However, the roles of PLC and PKC in CCK-mediated anxiogenic effects have not been determined. We have shown previously that CCK facilitates glutamate release in the hippocampus especially at the synapses formed by the perforant path and dentate gyrus granule cells via activations of PLC and PKC. Here we further demonstrated that CCK enhanced NMDA receptor function in dentate gyrus granule cells via activation of PLC and PKC pathway. At the single-channel level, CCK increased NMDA single-channel open probability and mean open time, reduced the mean close time, and had no effects on the conductance of NMDA channels. Because elevation of glutamatergic functions results in anxiety, we explored the roles of PLC and PKC in CCK-induced anxiogenic actions using the Vogel Conflict Test (VCT). Our results from both pharmacological approach and knockout mice demonstrated that microinjection of CCK into the dentate gyrus concentration dependently increased anxiety-like behavior via activation of PLC and PKC. Our results provide a novel unidentified signaling mechanism whereby CCK increases anxiety. PMID- 22072553 TI - Identification and characterization of Hoxa9 binding sites in hematopoietic cells. AB - The clustered homeobox proteins play crucial roles in development, hematopoiesis, and leukemia, yet the targets they regulate and their mechanisms of action are poorly understood. Here, we identified the binding sites for Hoxa9 and the Hox cofactor Meis1 on a genome-wide level and profiled their associated epigenetic modifications and transcriptional targets. Hoxa9 and the Hox cofactor Meis1 cobind at hundreds of highly evolutionarily conserved sites, most of which are distant from transcription start sites. These sites show high levels of histone H3K4 monomethylation and CBP/P300 binding characteristic of enhancers. Furthermore, a subset of these sites shows enhancer activity in transient transfection assays. Many Hoxa9 and Meis1 binding sites are also bound by PU.1 and other lineage-restricted transcription factors previously implicated in establishment of myeloid enhancers. Conditional Hoxa9 activation is associated with CBP/P300 recruitment, histone acetylation, and transcriptional activation of a network of proto-oncogenes, including Erg, Flt3, Lmo2, Myb, and Sox4. Collectively, this work suggests that Hoxa9 regulates transcription by interacting with enhancers of genes important for hematopoiesis and leukemia. PMID- 22072554 TI - NF-Y is necessary for hematopoietic stem cell proliferation and survival. AB - HSC function depends on the tight control of proliferation and the balance between self-renewal and differentiation. Here, we report that the trimeric transcription factor NF-Y is critical for the survival of cycling, but not quiescent HSCs. With the use of a conditional knockout mouse model, we demonstrate that NF-Ya deletion creates an accumulation of HSCs in G(2)/M and prompts apoptosis, causing hematopoietic failure and death of the animal. These defects are accompanied by the dysregulation of multiple genes that influence cell cycle control (cyclin b1 and p21), apoptosis (Bcl-2), and self-renewal (HoxB4, Notch1, Bmi-1) and are independent of p53. Our results identify NF-Y as a pivotal upstream participant in a regulatory network necessary for the preservation of cycling HSCs. PMID- 22072555 TI - Distinct graft-versus-leukemic stem cell effects of early or delayed donor leukocyte infusions in a mouse chronic myeloid leukemia model. AB - Among hematologic neoplasms, chronic myeloid leukemia (CML) is exquisitely sensitive to graft-versus-leukemia (GVL) because patients relapsing after allogeneic hematopoietic stem-cell transplantation (alloHSCT) can be cured by donor leukocyte infusion (DLI); however, the cellular mechanisms and strategies to separate GVL from GVHD are unclear. We used a BCR-ABL1 transduction/transplantation mouse model to study the mechanisms of DLI in MHC matched, minor histocompatibility antigen-mismatched allogeneic chimeras with CML like leukemia, in which DLI can be administered at the time of transplantation (early) or after recovery of hematopoiesis (delayed). After early DLI, CML-like leukemia cannot be transferred into immunocompetent secondary recipients as soon as 4 days after primary transplantation, demonstrating that cotransplantation of T lymphocytes blocks the engraftment of BCR-ABL1-transduced stem cells. In contrast, in allogeneic chimeras with established CML-like leukemia, combined treatment with delayed DLI and the kinase inhibitor imatinib eradicates leukemia with minimal GVHD. The GVL effect is directed against minor histocompatibility antigens shared by normal and leukemic stem cells, and is mediated predominantly by CD8+ T cells, with minor contributions from CD5- splenocytes, including natural killer cells. These results define a physiologic model of adoptive immunotherapy of CML that will be useful for investigating the cellular and molecular mechanisms of GVL. PMID- 22072556 TI - Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans. AB - Chronic GVHD (cGVHD) poses a significant risk for HSCT patients. Preclinical development of new therapeutic modalities has been hindered by models with pathologic findings that may not simulate the development of human cGVHD. Previously, we have demonstrated that cGVHD induced by allogeneic HSCT after a conditioning regimen of cyclophosphamide and total-body radiation results in pulmonary dysfunction and airway obliteration, which leads to bronchiolitis obliterans (BO), which is pathognomonic for cGVHD of the lung. We now report cGVHD manifestations in a wide spectrum of target organs, including those with mucosal surfaces. Fibrosis was demonstrated in the lung and liver and was associated with CD4(+) T cells and B220(+) B-cell infiltration and alloantibody deposition. Donor bone marrow obtained from mice incapable of secreting IgG alloantibody resulted in less BO and cGVHD. Robust germinal center reactions were present at the time of cGVHD disease initiation. Blockade of germinal center formation with a lymphotoxin-receptor-immunoglobulin fusion protein suppressed cGVHD and BO. We conclude that cGVHD is caused in part by alloantibody secretion, which is associated with fibrosis and cGVHD manifestations including BO, and that treatment with a lymphotoxin-beta receptor-immunoglobulin fusion protein could be beneficial for cGVHD prevention and therapy. PMID- 22072557 TI - The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms. AB - The somatically acquired V600E mutation of the BRAF gene has been recently described as a molecular marker of hairy cell leukemia (HCL). We developed an allele-specific PCR for this mutation and studied 62 patients with HCL, 1 with HCL variant, 91 with splenic marginal zone lymphoma, 29 with Waldenstrom macroglobulinemia, and 57 with B-cell chronic lymphoproliferative disorders. The BRAF V600E mutation was detected in all HCL cases and in only 2 of the remaining 178 patients. These 2 subjects had B-cell chronic lymphoproliferative disorders that did not fulfill the diagnostic criteria for HCL. Despite the positive PCR finding, the mutation could not be detected by Sanger sequencing in these 2 cases, suggesting that it was associated with a small subclone. We conclude that the BRAF V600E mutation is present in all patients with HCL and that, in combination with clinical and morphologic features, represents a reliable molecular marker for this condition. PMID- 22072558 TI - An intermediate-risk multiple myeloma subgroup is defined by sIL-6r: levels synergistically increase with incidence of SNP rs2228145 and 1q21 amplification. AB - IL-6 signaling can be enhanced through transsignaling by the soluble IL-6 receptor (sIL-6r), allowing for the pleiotropic cytokine to affect cells it would not ordinarily have an effect on. Serum levels of sIL-6r can be used as an independent prognostic indicator and further stratify the GEP 70-gene low-risk group to identify an intermediate-risk group in multiple myeloma (MM). By analyzing more than 600 MM patients with ELISA, genotyping, and gene expression profiling tools, we show how the combination of 2 independent molecular genetic events is related to synergistic increases in sIL-6r levels. We also show that the rs2228145 minor allele is related to increased expression levels of an IL-6r splice variant that purportedly codes exclusively for a sIL-6r isoform. Together, the SNP rs2228145 minor allele C and amplification of chromosome 1q21 are significantly correlated to an increase in sIL-6r levels, which are associated with lower overall survival in 70-gene low-risk disease, and aid in identification of the intermediate-risk MM group. PMID- 22072559 TI - Emergence of NK-cell progenitors and functionally competent NK-cell lineage subsets in the early mouse embryo. AB - The earliest stages of natural killer (NK)-cell development are not well characterized. In this study, we investigated in different fetal hematopoietic tissues how NK-cell progenitors and their mature NK-cell progeny emerge and expand during fetal development. Here we demonstrate, for the first time, that the counterpart of adult BM Lin(-)CD122(+)NK1.1(-)DX5(-) NK-cell progenitor (NKP) emerges in the fetal liver at E13.5. After NKP expansion, immature NK cells emerge at E14.5 in the liver and E15.5 in the spleen. Thymic NK cells arise at E15.5, whereas functionally competent cytotoxic NK cells were present in the liver and spleen at E16.5 and E17.5, respectively. Fetal NKPs failed to produce B and myeloid cells but sustained combined NK- and T-lineage potential at the single-cell level. NKPs were also found in the fetal blood, spleen, and thymus. These findings show the emergence and expansion of bipotent NK/T-cell progenitor during fetal and adult lymphopoiesis, further supporting that NK/T-lineage restriction is taking place prethymically. Uncovering the earliest NK-cell developmental stages will provide important clues, helping to understand the origin of diverse NK-cell subsets, their progenitors, and key regulators. PMID- 22072560 TI - Three-dimensional repositioning tasks show differences in joint position sense between active and passive shoulder motion. AB - Proprioception is important in maintaining shoulder joint stability. Previous studies investigated the effects of unconstrained multiplanar motion, with subjects able to move freely in space, on repositioning tasks for active shoulder motion but not passive motion. We sought to further explore joint position sense with 3D passive, robot-guided motions. We hypothesized that target repositioning error would be greater in the case of passively placed targets than for actively placed targets. To investigate, 15 healthy individuals participated (8 female, 7 male), who were at most 6 ft (183 cm) tall to accommodate the equipment, and who had no history of shoulder injury, surgery, or significant participation in throwing sports. Target orientations were centered at 44 degrees of elevation and 32 degrees of horizontal rotation from the frontal plane. Two sets of 10 trials were performed. The first set involved active placement followed by active replacement, and the second set involved passive, robot-guided, placement followed by active replacement. Repositioning error was greater following passive placement than active placement (p < 0.001). These results further our understanding of the differences between active and passive joint position sense at the shoulder. PMID- 22072561 TI - Interstitial fluid pressure correlates with intravoxel incoherent motion imaging metrics in a mouse mammary carcinoma model. AB - The effective delivery of a therapeutic drug to the core of a tumor is often impeded by physiological barriers, such as the interstitial fluid pressure (IFP). There are a number of therapies that can decrease IFP and induce tumor vascular normalization. However, a lack of a noninvasive means to measure IFP hinders the utilization of such a window of opportunity for the maximization of the treatment response. Thus, the purpose of this study was to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion parameters as noninvasive imaging biomarkers for IFP. Mice bearing the 4T1 mammary carcinoma model were studied using diffusion-weighted imaging (DWI), immediately followed by wick-in needle IFP measurement. Voxelwise analysis was conducted with a conventional monoexponential diffusion model, as well as a biexponential model taking IVIM into account. There was no significant correlation of IFP with either the median apparent diffusion coefficient from the monoexponential model (r = 0.11, p = 0.78) or the median tissue diffusivity from the biexponential model (r = 0.30, p = 0.44). However, IFP was correlated with the median pseudo-diffusivity (D(p)) of apparent vascular voxels (r = 0.76, p = 0.02) and with the median product of the perfusion fraction and pseudo-diffusivity (f(p)D(p)) of apparent vascular voxels (r = 0.77, p = 0.02). Although the effect of IVIM in tumors has been reported previously, to our knowledge, this study represents the first direct comparison of IVIM metrics with IFP, with the results supporting the feasibility of the use of IVIM DWI metrics as noninvasive biomarkers for tumor IFP. PMID- 22072562 TI - Staging of multivessel percutaneous coronary interventions: an expert consensus statement from the Society for Cardiovascular Angiography and Interventions. AB - Percutaneous coronary interventions (PCIs) to treat multivessel coronary artery disease (MVCAD) may involve single-vessel or multivessel interventions, performed in one or more stages. This consensus statement reviews factors that may influence choice of strategy and includes six recommendations to guide decisions regarding staging of PCI. Every patient who undergoes PCI should receive optimal therapy for coronary disease, ideally before starting the procedure. Multivessel PCI at the time of diagnostic catheterization should be considered only if informed consent included the risks and benefits of multivessel PCI and the risks and benefits of alternative treatments. When considering multivessel PCI, the interventionist should develop a strategy regarding which stenoses to treat or evaluate, and their order, method, and timing. This strategy should maximize patient benefits, minimize patient risk, and consider the factors described in this article. For planned multivessel PCI, additional vessel(s) should be treated only if the first vessel is treated successfully and if anticipated contrast and radiation doses and patient and operator conditions are favorable. After the first stage of the planned multistage PCI, the need for subsequent PCI should be reviewed before it is performed. Third party payers and quality auditors should recognize that multistage PCI for MVCAD is neither an indication of poor quality nor an attempt to increase reimbursement when performed according to recommendations in this article. PMID- 22072563 TI - Tryptophan side chain conformers monitored by NMR and time-resolved fluorescence spectroscopies. AB - We have inserted a tryptophan (F77W) in the core of the regulatory domain of cardiac troponin C (cNTnC), and previously determined the structure of this mutant with and without the cosolvent trifluoroethanol (TFE). Interestingly, the orientations of the indole side chain of the Trp are in opposite directions in the two structures (Julien et al., Protein Sci 2009; 18:1165-1174). Fluorescence decay experiments for single Trp-containing proteins often show several lifetimes, which have been interpreted as reflecting conformational heterogeneity of the Trp side chain resulting from different rotamers. To test this interpretation, we monitored the effect of TFE on wild type, F77W and F77W-V82A calcium-saturated cNTnC using 2D (13)C-HSQC NMR and time-correlated single photon counting fluorescence spectroscopies. The time dependence of the Trp fluorescence decay was fit with three lifetimes. Addition of TFE caused a gradual, but limited decrease of the lifetimes due to dynamic quenching. For F77W cNTnC, the amplitude fractions of the lifetimes also changed upon addition of TFE-the long lifetime increased from 13 to 29%, while the middle lifetime decreased from 63 to 50% and the short lifetime remained relatively unchanged. For F77W-V82A cNTnC, comparable NMR changes are observed, confirming the switch in rotamer conformation, but only much smaller changes in fluorescence decay parameters were detected. These data indicate that the balance between the rotamer states can be changed without changing the lifetime amplitude fractions appreciably, and suggest that the environment(s) of the indole ring, responsible for the different lifetimes, can result from factors other than the intrinsic rotamer state of the tryptophan. PMID- 22072564 TI - Developmental profile of SK2 channel expression and function in CA1 neurons. AB - We investigated the temporal and spatial expression of SK2 in the developing mouse hippocampus using molecular and biochemical techniques, quantitative immunogold electron microscopy, and electrophysiology. The mRNA encoding SK2 was expressed in the developing and adult hippocampus. Western blotting and immunohistochemistry showed that SK2 protein increased with age. This was accompanied by a shift in subcellular localization. Early in development (P5), SK2 was predominantly localized to the endoplasmic reticulum in the pyramidal cell layer. But by P30 SK2 was almost exclusively expressed in the dendrites and spines. The level of SK2 at the postsynaptic density (PSD) also increased during development. In the adult, SK2 expression on the spine plasma membrane showed a proximal-to-distal gradient. Consistent with this redistribution and gradient of SK2, the selective SK channel blocker apamin increased evoked excitatory postsynaptic potentials (EPSPs) only in CA1 pyramidal neurons from mice older than P15. However, the effect of apamin on EPSPs was not different between synapses in proximal or distal stratum radiatum or stratum lacunosum-moleculare in adult. These results show a developmental increase and gradient in SK2 containing channel surface expression that underlie their influence on neurotransmission, and that may contribute to increased memory acquisition during early development. PMID- 22072565 TI - A possible overestimation of the effect of acetylation on lysine residues in KQ mutant analysis. AB - Acetylation of lysine residues, one of the most common protein post transcriptional modifications, is thought to regulate protein affinity with other proteins or nucleotides. Experimentally, the effects of acetylation have been studied using recombinant mutants in which lysine residues (K) are substituted with glutamine (Q) as a mimic of acetyl lysine (KQ mutant), or with arginine (R) as a mimic of nonacetylated lysine (KR mutant). These substitutions, however, have not been properly validated. The effects lysine acetylation on Ku, a multifunctional protein that has been primarily implicated in DNA repair and cell survival, are characterized herein using a series of computer simulations. The binding free energy was reduced in the KQ mutant, while the KR mutant had no effect, which is consistent with previous experimental results. Unexpectedly, the binding energy between Ku and DNA was maintained at almost the same level as in the wild type protein despite full acetylation of the lysine residues. These results suggest that the effects of acetylation may be overestimated when the KQ mutant is used as a mimic of the acetylated protein. PMID- 22072566 TI - Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER independent mediator of endocrine-resistant breast cancer. AB - The development of breast cancer resistance to endocrine therapy results from an increase in cellular plasticity that permits the emergence of a hormone independent tumor. The steroid coactivator protein SRC-1, through interactions with developmental proteins and other nonsteroidal transcription factors, drives this tumor adaptability. In this discovery study, we identified ADAM22, a non protease member of the ADAM family of disintegrins, as a direct estrogen receptor (ER)-independent target of SRC-1. We confirmed SRC-1 as a regulator of ADAM22 by molecular, cellular, and in vivo studies. ADAM22 functioned in cellular migration and differentiation, and its levels were increased in endocrine resistant-tumors compared with endocrine-sensitive tumors in mouse xenograft models of human breast cancer. Clinically, ADAM22 was found to serve as an independent predictor of poor disease-free survival. Taken together, our findings suggest that SRC-1 switches steroid-responsive tumors to a steroid-resistant state in which the SRC 1 target gene ADAM22 has a critical role, suggesting this molecule as a prognostic and therapeutic drug target that could help improve the treatment of endocrine-resistant breast cancer. PMID- 22072568 TI - Rigid-CLL: avoiding constant-distance computations in cell linked-lists algorithms. AB - Many of the existing molecular simulation tools require the efficient identification of the set of nonbonded interacting atoms. This is necessary, for instance, to compute the energy values or the steric contacts between atoms. Cell linked-lists can be used to determine the pairs of atoms closer than a given cutoff distance in asymptotically optimal time. Despite this long-term optimality, many spurious distances are anyway computed with this method. Therefore, several improvements have been proposed, most of them aiming to refine the volume of influence for each atom. Here, we suggest a different improvement strategy based on avoiding to fill cells with those atoms that are always at a constant distance of a given atom. This technique is particularly effective when large groups of the particles in the simulation behave as rigid bodies as it is the case in simplified models considering only few of the degrees of freedom of the molecule. In these cases, the proposed technique can reduce the number of distance computations by more than one order of magnitude, as compared with the standard cell linked-list technique. The benefits of this technique are obtained without incurring in additional computation costs, because it carries out the same operations as the standard cell linked-list algorithm, although in a different order. Since the focus of the technique is the order of the operations, it might be combined with existing improvements based on bounding the volume of influence for each atom. PMID- 22072567 TI - Radiosensitization of human pancreatic cancer cells by MLN4924, an investigational NEDD8-activating enzyme inhibitor. AB - Radiotherapy is used in locally advanced pancreatic cancers in which it can improve survival in combination with gemcitabine. However, prognosis is still poor in this setting in which more effective therapies remain needed. MLN4924 is an investigational small molecule currently in phase I clinical trials. MLN4924 inhibits NAE (NEDD8 Activating Enzyme), a pivotal regulator of the E3 ubiquitin ligase SCF (SKP1, Cullins, and F-box protein), that has been implicated recently in DNA damage and repair. In this study, we provide evidence that MLN4924 can be used as an effective radiosensitizer in pancreatic cancer. Specifically, MLN4924 (20-100 nmol/L) effectively inhibited cullin neddylation and sensitized pancreatic cancer cells to ionizing radiation in vitro with a sensitivity enhancement ratio of approximately 1.5. Mechanistically, MLN4924 treatment stimulated an accumulation of several SCF substrates, including CDT1, WEE1, and NOXA, in parallel with an enhancement of radiation-induced DNA damage, aneuploidy, G(2)/M phase cell-cycle arrest, and apoptosis. RNAi-mediated knockdown of CDT1 and WEE1 partially abrogated MLN4924-induced aneuploidy, G(2)/M arrest, and radiosensitization, indicating a causal effect. Furthermore, MLN4924 was an effective radiosensitizer in a mouse xenograft model of human pancreatic cancer. Our findings offer proof-of-concept for use of MLN4924 as a novel class of radiosensitizer for the treatment of pancreatic cancer. PMID- 22072569 TI - Public preferences for responsibility versus public preferences for reducing inequalities. AB - In cost-utility analysis, the numbers of quality-adjusted life years (QALYs) gained are aggregated by placing the same weight on each QALY. Deviations from this rubric have been proposed on a number of grounds, including the degree to which persons might be deemed responsible for the illness faced, and inequality in lifetime health between groups. Most research has looked at these factors in isolation. This paper analyses public preferences about the relative importance of these factors. Over 500 members of the general public in the UK are interviewed in their homes. Where "blameworthy" groups experience a moderate drop in quality of life due to their behaviour, they appear to receive higher priority than an otherwise "trustworthy" group if they also experience poorer health prospects because the latter is weighted more heavily than the former. PMID- 22072570 TI - Effect of partial meniscectomy at the medial posterior horn on tibiofemoral contact mechanics and meniscal hoop strains in human knees. AB - We examined the influence of partial meniscectomy of 10 mm width on 10 human cadaveric knee joints, as it is performed during the treatment of radial tears in the posterior horn of the medial meniscus, on maximum contact pressure, contact area (CA), and meniscal hoop strain in the lateral and medial knee compartments. In case of 0 degrees and 30 degrees flexion angle, 20% and 50% partial meniscectomy did not influence maximum contact pressure and area. Only in case of 60 degrees knee flexion, 50% partial resection increased medial maximum contact pressure and decreased the medial CA statistically significant. However, 100% partial resection increased maximum contact pressure and decreased CA significantly in the meniscectomized medial knee compartment in all tested knee positions. No significant differences were noted for meniscal hoop strain. From a biomechanical point of view, our in vitro study suggests that the medial joint compartment is not in danger of accelerated cartilage degeneration up to a resection limit of 20% meniscal depth and 10 mm width. Contact mechanics are likely to be more sensitive to partial meniscectomy at higher flexion angles, which has to be further investigated. PMID- 22072571 TI - Polymorphisms of stress-related genes and the risk of nonsyndromic cleft lip with or without cleft palate. AB - BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NCL/P) is a common structural malformation with a complex and multifactorial etiology. It has been shown that maternal psychological stress in the periconceptional period can contribute to an increase in the risk of NCL/P affecting pregnancy. METHODS: Twenty-four single nucleotide polymorphisms of 11 stress-related genes (COMT, CRHR1, FKBP5, GABRA6, HSD11beta2, MAOA, NPY, NR3C1, SERPINA6, SLC6A4, and TPH2) were investigated in 220 healthy mothers of children with facial clefts and 210 matched controls using restriction fragment-length polymorphism and high resolution melting analysis. RESULTS: We found that polymorphisms in SLC6A4, TPH2, and SERPINA6 appear to be maternal factors increasing the risk of having a child with facial clefts. The closest correlations with NCL/P were found for the SLC6A4 rs2020942 and TPH2 rs10879357 gene variants (odds ratio [OR], 1.720; 95% confidence interval [CI], 1.158-2.553; p = 0.0069; p(trend) = 0.0036; and OR, 1.837; 95% CI, 1.226-2.753, p = 0.0030, p(trend) = 0.0057; respectively). Moreover, haplotype analysis revealed that several combinations of markers in SLC6A4, TPH2, and SERPINA6 might be significantly associated with the risk of NCL/P affected pregnancies. However, these associations were not statistically significant after correction for multiple testing. CONCLUSION: This study suggests that nucleotide variants of genes encoding components of the hypothalamus-pituitary-adrenal axis and serotoninergic system have a role in the etiology of NCL/P in the Polish population. SLC6A4, TPH2, and SERPINA6 might be novel candidate genes for this common congenital anomaly. PMID- 22072572 TI - Carbidopa enhances antitumoral activity of bicalutamide on the androgen receptor axis in castration-resistant prostate tumors. AB - BACKGROUND: Response to bicalutamide after castration failure is not durable and treatment options at this stage are limited. Carbidopa, an L-dopa decarboxylase (AR-coactivator) inhibitor, has been shown to retard prostate tumor growth/PSA production in xenografts. Here, we hypothesize that pharmacological targeting of the AR-axis by combination treatment with bicalutamide plus carbidopa significantly enhances antitumoral activity in vitro and in vivo compared to monotherapy with either drug. METHODS: Carbidopa was tested for its ability to enhance the effects of bicalutamide on cell viability, apoptosis and PSA transactivation in LNCaP and C4-2 cells. The castration-resistant prostate cancer (CRPC) LNCaP xenograft tumor model was used in vivo. After CRPC progression, mice were treated with carbidopa (50 mg/kg) and bicalutamide (50 mg/kg) as monotherapy or in combination. Tumor volume and serum PSA were evaluated weekly. RESULTS: Combination treatment of carbidopa plus bicalutamide significantly inhibited cell viability in both cell lines and induced apoptosis. The combination treatment also decreased androgen-induced PSA transactivation by 62.6% in LNCaP cells and by 55.6% in C4-2 cells compared to control, while bicalutamide monotherapy reduced PSA levels by 27.5% and 29.1% in LNCaP and C4-2 cells. In vivo, bicalutamide monotherapy delayed LNCaP CRPC tumor growth rate by 72.2%, while combination treatment reduced tumor growth by 84.4% compared to control. Serum PSA was also reduced 70.6% with bicalutamide monotherapy, while combination therapy reduced PSA levels by 76.7% compared to control. CONCLUSIONS: This study demonstrates preclinical proof-of-principle that pharmacological targeting of prostate tumors by combination treatment of bicalutamide plus carbidopa significantly reduces AR activity, and thereby delays CRPC tumor progression in vivo. PMID- 22072573 TI - Structural and mechanical effects of in vivo fatigue damage induction on murine tendon. AB - The purpose of this study was to develop and validate an in vivo mouse model of tendon fatigue and use this model to investigate and quantify the physical manifestations of fatigue damage in mouse tendon. Patellar tendons of C57BL/6J mice were fatigue loaded at 2 Hz to three endpoints (4 N peak force per cycle for 1 h, 6 N for 1 h, and 4 N for 2 h), during which hysteresis, tangent stiffness, and peak strain of each cycle were measured. Damage accumulation was then quantified using in situ histology, and each tendon was loaded monotonically to failure. Histological damage increased significantly in all three groups (>=2 fold), and monotonic stiffness decreased significantly in the 6 N, 1 h and 4 N, 2 h groups (~25%), suggesting that damage initially manifests as changes to the collagen structure of the tendon and subsequently as changes to the function. For the fatigue loading protocols used in this study, none of the evaluated real-time parameters from fatigue loading correlated with damage area fraction measured structural damage or monotonic stiffness, suggesting that they are not suited to serve as proxies for damage accumulation. In future studies, this model will be used to compare the biological response of mouse tendon to fatigue damage across genetic strains. PMID- 22072574 TI - Tbx5 overexpression favors a first heart field lineage in murine embryonic stem cells and in Xenopus laevis embryos. AB - The T-box transcription factor Tbx5 is involved in several developmental processes including cardiogenesis. Early steps of cardiac development are characterised by the formation of two cardiogenic lineages, the first (FHF) and the second heart field (SHF) lineage, which arise from a common cardiac progenitor cell population. To further investigate the function of Tbx5 during cardiogenesis, we generated a murine embryonic stem cell line constitutively overexpressing Tbx5. Differentiation of these cells is characterised by an earlier and increased appearance of contracting cardiomyocytes that beat with a higher frequency than control cells. In semi-quantitative and quantitative RT-PCR analyses, we observed an up-regulation of cardiac marker genes such as Troponin T, endogenous Tbx5, and Nkx2.5 and a down-regulation of others like BMP4 and Hand2. Similar data were gained in Xenopus laevis arguing for a conserved function of Tbx5. Furthermore, markers of the conduction system and atrial cardiomyocytes were increased. PMID- 22072575 TI - Deficiency in Crumbs homolog 2 (Crb2) affects gastrulation and results in embryonic lethality in mice. AB - The Crumbs family of transmembrane proteins has an important role in the differentiation of the apical membrane domain in various cell types, regulating such processes as epithelial cell polarization. The mammalian Crumbs protein family is composed of three members. Here, we inactivated the mouse Crb2 gene with gene-targeting techniques and found that the protein is crucial for early embryonic development with severe abnormalities appearing in Crb2-deficient embryos at late-gastrulation. Our findings indicate that the primary defect in the mutant embryos is disturbed polarity of the epiblast cells at the primitive streak, which affects epithelial to mesenchymal transition (EMT) during gastrulation, resulting in impaired mesoderm and endoderm formation, and embryonic lethality by embryonic day 12.5. These findings therefore indicate a novel role for the Crumbs family of proteins. PMID- 22072576 TI - Two promoters with distinct activities in different tissues drive the expression of heparanase in Xenopus. AB - In Xenopus laevis embryos, heparanase, the enzyme that degrades heparan sulfate, is synthesized as a preproheparanase (XHpaL) and processed to become enzymatically active (XHpa active). A short nonenzymatic heparanase splice variant (XHpaS) is also expressed. Using immunohistochemistry, Western blot, and heparanase promoter analysis, we studied the dynamic developmental expression of the three heparanases. Our results indicate that (1) all three isoforms are maternally expressed; (2) XHpaS is a developmental variant; (3) in the early embryo, heparanase is localized to both the plasma membrane and the nucleus; (4) several tissues express heparanase, but expression in the developing nervous system is most evident; (5) two promoters with distinct activities in different tissues drive heparanase expression; (6) Oct binding transcription factors may modulate heparanase promoter activity in the early embryo. These data argue that heparanase is expressed widely during development, but localization and levels are finely regulated. PMID- 22072577 TI - Primer and interviews: advances in targeted gene modification. Interview by Julie C. Kiefer. AB - Gene targeting in mice, first reported 25 years ago, has led to monumental advances in the understanding of basic biology and human disease. The ability to employ a similarly straightforward method for gene manipulation in other experimental organisms would make their already significant contributions all the more powerful. Here, we briefly outline the strengths and weaknesses of reverse genetics techniques in non-murine model organisms, ending with a more detailed description of two that promise to bring targeted gene modification to the masses: zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Dana Caroll, a forefather of zinc finger technology, and Bo Zhang, among the first to introduce TALEN-targeted mutagenesis to zebrafish, discuss their experience with these techniques, and speculate about the future of the field. PMID- 22072581 TI - Controlled ambipolar-to-unipolar conversion in graphene field-effect transistors through surface coating with poly(ethylene imine)/poly(ethylene glycol) films. AB - A controlled ambipolar-to-unipolar (n-type) conversion, along with a maximum fourfold increase in the electron mobility, in graphene field-effect transistors (FETs) is achieved by coating the surface of graphene with a layer of a mixed polymer system, poly(ethylene imine) (PEI) in poly(ethylene glycol) (PEG). The PEG serves as a physisorption adhesion agent for the PEI. Both unipolar and ambipolar n-type doping can be realized by adjusting the thickness of PEI films atop the graphene channel. The observed phenomena are attributed to the doping/dedoping effects of the external PEI film. The study provides a guide to engineering graphene transport properties through chemical modifications. PMID- 22072583 TI - Remote real-time monitoring of free flaps via smartphone photography and 3G wireless Internet: a prospective study evidencing diagnostic accuracy. AB - This prospective study was designed to compare the accuracy rate between remote smartphone photographic assessments and in-person examinations for free flap monitoring. One hundred and three consecutive free flaps were monitored with in person examinations and assessed remotely by three surgeons (Team A) via photographs transmitted over smartphone. Four other surgeons used the traditional in-person examinations as Team B. The response time to re-exploration was defined as the interval between when a flap was evaluated as compromised by the nurse/house officer and when the decision was made for re-exploration. The accuracy rate was 98.7% and 94.2% for in-person and smartphone photographic assessments, respectively. The response time of 8 +/- 3 min in Team A was statistically shorter than the 180 +/- 104 min in Team B (P = 0.01 by the Mann Whitney test). The remote smartphone photography assessment has a comparable accuracy rate and shorter response time compared with in-person examination for free flap monitoring. PMID- 22072582 TI - Inverse association between glutathione peroxidase activity and both selenium binding protein 1 levels and Gleason score in human prostate tissue. AB - BACKGROUND: Data from human epidemiological studies, cultured mammalian cells, and animal models have supported a potentially beneficial role of selenium (Se) in prostate cancer prevention. In addition, Se-containing proteins including members of the glutathione peroxidase (GPx) family and Selenium-Binding Protein 1 (SBP1) have been linked to either cancer risk or development. For example, SBP1 levels are typically reduced in tumors compared to non-cancerous tissue, with the degree of reduction associated with increasingly poor clinical outcome. METHODS: In order to investigate inter-relationships between blood and tissue Se levels and GPx activity, tissue SBP1 levels, and disease aggressiveness using the Gleason score, we measured levels of selenium and selected selenoproteins in fasting serum and histologically normal prostate tissues obtained from 24 men undergoing radical prostatectomy for the treatment of localized prostate cancer. RESULTS: GPx enzyme activity was inversely correlated with SBP1 levels in prostate tissue as determined by densitometry of Western blots obtained using anti-SBP1 antibodies [partial Spearman's correlation coefficients and corresponding P-values overall and in African-Americans = -0.42 (0.08) and -0.53 (0.10), respectively], which is consistent with previous observations in cultured cells and mice. Of particular interest was the positive correlation between tissue GPx activity and Gleason score, with this relationship achieving statistical significance among African-Americans (r = 0.67, P = 0.02). CONCLUSION: These studies support the continued investigation of the role of Se and selenoproteins in prostate cancer prevention, development, and prognosis. PMID- 22072584 TI - Peripheral nerve reconstruction with collagen tubes filled with denatured autologous muscle tissue in the rat model. AB - Conventional nerve conduits lack cellular and extracellular guidance structures critical for bridging larger defects. In this study, an exogenous matrix for axonal regeneration was provided by pretreated muscle tissue. In 24 rats, 14-mm sciatic nerve segments were resected and surgically reconstructed using one of the following methods: autograft (AG); bovine type I collagen conduit; (MDM) collagen tube filled with modified denatured autologous muscle tissue. For 8 weeks, functional regeneration was evaluated by footprint and video gait analysis. Evaluation was complemented by electrophysiology, as well as qualitative and quantitative structural assessment of nerves and target muscles. Group AG was superior both structurally and functionally, showing higher axon counts, a more normal gait pattern, and less severe muscle atrophy. Fiber quality (fiber size and myelin thickness) was highest in group MDM, possibly related to the myelin-producing effect of muscular laminin. However, axon count was lowest in this group, and ultrastructural analysis of the denatured muscle tissue showed areas of incomplete denaturation that had acted as a mechanical barrier for regenerating axons. In light of these results, the often advocated use of muscular exogenous matrix for peripheral nerve reconstruction is reviewed in the literature, and its clinical application is critically discussed. In conclusion, combined muscle tubes may have a positive influence on nerve fiber maturation. However, muscle pretreatment is not without risks, and denaturation processes need to be further refined. PMID- 22072585 TI - Probing diffusion of single nanoparticles at water-oil interfaces. AB - The diffusion of nanoparticles at a water-alkane interface is studied using fluorescence correlation spectroscopy. Hydrophilic and hydrophobic quantum dots of 5, 8, and 11 nm radius are used. A slow-down of nanoparticle diffusion at the liquid-liquid interface is observed. The effect is most evident when the viscosities of both liquid phases are similar, here, at the water-decane interface. In this case, the interfacial diffusion coefficients of the hydrophilic particles are 1.5 times and those of the hydrophobic particles 2 times lower than the corresponding bulk values. PMID- 22072586 TI - Cassettes for PCR-mediated gene tagging in Candida albicans utilizing nourseothricin resistance. AB - In recent years a number of molecular tools have been reported for use in the human fungal pathogen Candida albicans, including PCR-mediated approaches for gene disruption, conditional expression and epitope tagging. Traditionally these methods have utilized auxotrophic markers; however, the availability of auxotrophic markers can be limiting and in some instances their use may also impact on the interpretation of results. As a result, the use of positive selection markers has now become more commonplace. Here we report the development and validation of a set of cassettes for PCR-mediated gene tagging and overexpression studies utilizing the nourseothricin resistance (CaNAT1) positive selection marker. In particular we have produced cassettes containing yeast enhanced GFP, YFP, CFP, RFP and a combined V5-6xHis epitope tag. The cassettes are engineered for use in PCR-mediated gene tagging strategies where insertion is targeted to the 3' end of the gene of interest. In addition, to facilitate protein functional analysis and genetic suppression studies through the use of overexpression, we have also constructed a promoter replacement cassette containing the ENO1 promoter which is known to be expressed at a high level. These cassettes expand on the range of molecular tools available for working with C. albicans and may also be used in other Candida species that display sensitivity to nourseothricin. PMID- 22072587 TI - Posttranscriptional upregulation by microRNAs. AB - MicroRNAs are small non-coding RNA guide molecules that regulate gene expression via association with effector complexes and sequence-specific recognition of target sites on other RNAs; misregulated microRNA expression and functions are linked to a variety of tumors, developmental disorders, and immune disease. MicroRNAs have primarily been demonstrated to mediate posttranscriptional downregulation of expression; translational repression, and deadenylation dependent decay of messages through partially complementary microRNA target sites in mRNA untranslated regions (UTRs). However, an emerging assortment of studies, discussed in this review, reveal that microRNAs and their associated protein complexes (microribonucleoproteins or microRNPs) can additionally function to posttranscriptionally stimulate gene expression by direct and indirect mechanisms. These reports indicate that microRNA-mediated effects can be selective, regulated by the RNA sequence context, and associated with RNP factors and cellular conditions. Like repression, translation upregulation by microRNAs has been observed to range from fine-tuning effects to significant alterations in expression. These studies uncover remarkable, new abilities of microRNAs and associated microRNPs in gene expression control and underscore the importance of regulation, in cis and trans, in directing appropriate microRNP responses. PMID- 22072590 TI - Height loss predicts subsequent hip fracture in men and women of the Framingham Study. AB - Although height is a risk factor for osteoporotic fracture, current risk assessments do not consider height loss. Height loss may be a simple measurement that clinicians could use to predict fracture or need for further testing. The objective was to examine height loss and subsequent hip fracture, evaluating both long-term adult height loss and recent height loss. Prospective cohort of 3081 adults from the Framingham Heart Study. Height was measured biennially since 1948, and cohort followed for hip fracture through 2005. Adult height loss from middle-age years across 24 years and recent height loss in elderly years were considered. Cox proportional hazard regression was used to estimate association between height loss and risk of hip fracture. Of 1297 men and 1784 women, mean baseline age was 66 years (SD = 7.8). Average height loss for men was 1.06 inches (0.76), and for women was 1.12 inches (0.84). A total of 11% of men and 15% of women lost >=2 inches of height. Mean follow-up was 17 years, during which 71 men and 278 women had incident hip fractures. For each 1-inch of height loss, hazard ratio (HR) = 1.4 in men [95% confidence interval (CI): 1.00, 1.99], and 1.04 in women (95% CI: 0.88, 1.23). Men and women who lost >=2 inches of height had increased fracture risk (compared with 0 to <2 inches) of borderline significance: men HR = 1.8, 95% CI: 0.86, 3.61; women HR = 1.3, 95% CI: 0.90, 1.76. Recent height loss in elders significantly increased the risk of hip fracture, 54% in men and 21% in women (95% CI: 1.14, 2.09; 1.03, 1.42, respectively). Adult height loss predicted hip fracture risk in men in our study. Recent height loss in elderly men and women predicted risk of hip fracture. PMID- 22072591 TI - Next-generation sequencing in molecular diagnosis: NUBPL mutations highlight the challenges of variant detection and interpretation. AB - Next-generation sequencing (NGS) is transitioning from being a research tool to being used in routine genetic diagnostics, where a major challenge is distinguishing which of many sequence variants in an individual are truly pathogenic. We describe some limitations of in silico analyses of NGS data that emphasize the need for experimental confirmation. Using NGS, we recently identified an apparently homozygous missense mutation in NUBPL in a patient with mitochondrial complex I deficiency. Causality was established via lentiviral correction studies with wild-type NUBPL cDNA. NGS data, however, provided an incomplete understanding of the genetic abnormality. We show that the maternal allele carries an unbalanced inversion, while the paternal allele carries a branch-site mutation in addition to the missense mutation. We demonstrate that the branch-site mutation, which is present in approximately one of 120 control chromosomes, likely contributes to pathogenicity and may be one of the most common autosomal mutations causing mitochondrial dysfunction. Had these analyses not been performed following NGS, the original missense mutation may be incorrectly annotated as pathogenic and a potentially common pathogenic variant not detected. It is important that locus-specific databases contain accurate information on pathogenic variation. NGS data, therefore, require rigorous experimental follow-up to confirm mutation pathogenicity. PMID- 22072592 TI - Cyclic RGD-polyethylene glycol-polyethylenimine for intracranial glioblastoma targeted gene delivery. AB - Even though the blood-brain barrier (BBB) is compromised for angiogenesis, therapeutic agents for glioblastoma multiforme (GBM) are particularly inefficient due to the existence of a blood-tumor barrier (BTB), which hampers tumor accumulation and uptake. Integrin alpha(v)beta(3) is overexpressed on glioblastoma U87 cells and neovasculture, thus making its ligands such as the RGD motif target glioblastoma in vitro and in vivo. In the present work, we have designed a modified polyethylene glycol-polyethylenimine (PEG-PEI) gene carrier by conjugating it with a cyclic RGD sequence, c(RGDyK) (cyclic arginine-glycine aspartic acid-D-tyrosine-lysine). When complexed with plasmid DNA, this gene carrier, termed RGD-PEG-PEI, formed homogenous nanoparticles with a mean diameter of 73 nm. These nanoparticles had a high binding affinity with U87 cells and facilitated targeted gene delivery against intracranial glioblastoma in vivo, thereby leading to a higher gene transfer efficiency compared to the PEG-PEI gene carrier without RGD decoration. This intracranial glioblastoma-targeted gene carrier also enhanced the therapeutic efficacy of pORF-hTRAIL, as evidenced by a significantly prolonged survival of intracranial glioblastoma-bearing nude mice. Considering the contribution of glioblastoma neovasculature to the BBB under angiogenic conditions, our results demonstrated the therapeutic feasibility of treating a brain tumor through mediation of integrin alpha(v)beta(3), as well as the potential of using RGD-PEG-PEI as a targeted gene carrier in the treatment of intracranial glioblastoma. PMID- 22072593 TI - Height loss in older women: risk of hip fracture and mortality independent of vertebral fractures. AB - We examined if height loss in older women predicts risk of hip fractures, other nonspine fractures, and mortality, and whether this risk is independent of both vertebral fractures (VFx) and bone mineral density (BMD) by dual-energy X-ray absorptiometry. Among 3124 women age 65 and older in the Study of Osteoporotic Fractures, we assessed the association with measured height change between year 0 (1986-1988) and year 15 (2002-2004) and subsequent risk of radiologically confirmed hip fractures, other nonspine fractures, and mortality assessed via death certificates. Follow-up occurred every 4 months for fractures and vital status (>95% contacts complete). Cox proportional hazards models assessed risk of hip fracture, nonspine fracture, and mortality over a mean of 5 years after height change was assessed (ie, after final height measurement). After adjustment for VFx, BMD, and other potential covariates, height loss >5 cm was associated with a marked increased risk of hip fracture [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.06, 2.12], nonspine fracture (HR 1.48; 95% CI 1.20, 1.83), and mortality (1.45; 95% CI 1.21, 1.73). Although primary analyses were a subset of 3124 survivors healthy enough to return for a year 15 height measurement, a sensitivity analysis in the entire cohort (n = 9677) using initial height in earlier adulthood [self-reported height at age 25 (-40 years) to measured height age >65 years (Year 0)] demonstrated consistent results. Height loss >5 cm (2") in older women was associated with a nearly 50% increased risk of hip fracture, nonspine fracture, and mortality-independent of incident VFx and BMD. PMID- 22072594 TI - Oligomerization of SLC4A11 protein and the severity of FECD and CHED2 corneal dystrophies caused by SLC4A11 mutations. AB - Mutations in the SLC4A11 gene, which encodes a plasma membrane borate transporter, cause recessive congenital hereditary endothelial corneal dystrophy type 2 (CHED2), corneal dystrophy and perceptive deafness (Harboyan syndrome), and dominant late-onset Fuchs endothelial corneal dystrophy (FECD). We analyzed missense SLC4A11 mutations identified in FECD and CHED2 patients and expressed in transfected HEK 293 cells. Chemical cross-linking and migration in nondenaturing gels showed that SLC4A11 exists as a dimer. Furthermore, co-immunoprecipitation of epitope-tagged proteins revealed heteromeric interactions between wild-type (WT) and mutant SLC4A11 proteins. When expressed alone, FECD- and CHED2-causing mutant SLC4A11 proteins are primarily retained intracellularly. Co-expression with WT SLC4A11 partially rescued the cell surface trafficking of CHED2 mutants, but not FECD mutants. CHED2 alleles of SLC4A11 did not affect cell surface processing of WT SLC4A11. In contrast, FECD mutants reduced WT cell surface processing efficiency, consistent with dominant inheritance of FECD. The reduction in movement of WT protein to the cell surface caused by FECD SLC4A11 helps to explain the dominant inheritance of this disorder. Similarly, the failure of CHED2 mutant SLC4A11 to affect the processing of WT protein, explains the lack of symptoms found in CHED2 carriers and the recessive inheritance of the disorder. PMID- 22072595 TI - Ca-rich Ca-Al-oxide, high-temperature-stable sorbents prepared from hydrotalcite precursors: synthesis, characterization, and CO2 capture capacity. AB - We present the design and synthesis of Ca-rich Ca-Al-O oxides, with Ca(2+)/Al(3+) ratios of 1:1, 3:1, 5:1, and 7:1, which were prepared by hydrothermal decomposition of coprecipitated hydrotalcite-like Ca-Al-CO(3) precursors, for high-temperature CO(2) adsorption at 500-700 degrees C. In situ X-ray diffraction measurements indicate that the coprecipitated, Ca-rich, hydrotalcite like powders with Ca(2+)/Al(3+) ratios of 5:1 and 7:1 contained Ca(OH)(2) and layered double hydroxide (LDH) phases. Upon annealing, LDH was first destroyed at approximately 200 degrees C to form an amorphous matrix, and then at 450-550 degrees C, the Ca(OH)(2) phase was converted into a CaO matrix with incorporated Al(3+) to form a homogeneous solid solution without a disrupted lattice structure. CaO nanocrystals were grown by thermal treatment of the weakly crystalline Ca-Al-O oxide matrix. Thermogravimetric analysis indicates that a CO(2) adsorption capacity of approximately 51 wt. % can be obtained from Ca-rich Ca-Al-O oxides prepared by calcination of 7:1 Ca-Al-CO(3) LDH phases at 600-700 degrees C. Furthermore, a relatively high CO(2) capture capability can be achieved, even with gas flows containing very low CO(2) concentrations (CO(2)/N(2) = 10 %). Approximately 95.6 % of the initial CO(2) adsorption capacity of the adsorbent is retained after 30 cycles of carbonation-calcination. TEM analysis indicates that carbonation-promoted CaCO(3) formation in the Ca-Al-O oxide matrix at 600 degrees C, but a subsequent desorption in N(2) at 700 degrees C, caused the formation CaO nanocrystals of approximately 10 nm. The CaO nanocrystals are widely distributed in the weakly crystalline Ca-Al-O oxide matrix and are present during the carbonation-calcination cycles. This demonstrates that Ca-Al-O sorbents that developed through the synthesis and calcination of Ca-rich Ca-Al LDH phases are suitable for long-term cyclic operation in severe temperature environments. PMID- 22072596 TI - Extension of the modified Poisson regression model to prospective studies with correlated binary data. AB - The Poisson regression model using a sandwich variance estimator has become a viable alternative to the logistic regression model for the analysis of prospective studies with independent binary outcomes. The primary advantage of this approach is that it readily provides covariate-adjusted risk ratios and associated standard errors. In this article, the model is extended to studies with correlated binary outcomes as arise in longitudinal or cluster randomization studies. The key step involves a cluster-level grouping strategy for the computation of the middle term in the sandwich estimator. For a single binary exposure variable without covariate adjustment, this approach results in risk ratio estimates and standard errors that are identical to those found in the survey sampling literature. Simulation results suggest that it is reliable for studies with correlated binary data, provided the total number of clusters is at least 50. Data from observational and cluster randomized studies are used to illustrate the methods. PMID- 22072597 TI - Protein-protein interaction sites are hot spots for disease-associated nonsynonymous SNPs. AB - Many nonsynonymous single nucleotide polymorphisms (nsSNPs) are disease causing due to effects at protein-protein interfaces. We have integrated a database of the three-dimensional (3D) structures of human protein/protein complexes and the humsavar database of nsSNPs. We analyzed the location of nsSNPS in terms of their location in the protein core, at protein-protein interfaces, and on the surface when not at an interface. Disease-causing nsSNPs that do not occur in the protein core are preferentially located at protein-protein interfaces rather than surface noninterface regions when compared to random segregation. The disruption of the protein-protein interaction can be explained by a range of structural effects including the loss of an electrostatic salt bridge, the destabilization due to reduction of the hydrophobic effect, the formation of a steric clash, and the introduction of a proline altering the main-chain conformation. PMID- 22072598 TI - Investigation of different cell types and gel carriers for cell-based intervertebral disc therapy, in vitro and in vivo studies. AB - Biological treatment options for the repair of intervertebral disc damage have been suggested for patients with chronic low back pain. The aim of this study was to investigate possible cell types and gel carriers for use in the regenerative treatment of degenerative intervertebral discs (IVD). In vitro: human mesenchymal cells (hMSCs), IVD cells (hDCs), and chondrocytes (hCs) were cultivated in three gel types: hyaluronan gel (Durolane(r)), hydrogel (Puramatrix(r)), and tissue glue gel (TISSEEL(r)) in chondrogenic differentiation media for 9 days. Cell proliferation and proteoglycan accumulation were evaluated with microscopy and histology. In vivo: hMSCs or hCs and hyaluronan gel were co-injected into injured IVDs of six minipigs. Animals were sacrificed at 3 or 6 months. Transplanted cells were traced with anti-human antibodies. IVD appearance was visualized by MRI, immunohistochemistry, and histology. Hyaluronan gel induced the highest cell proliferation in vitro for all cell types. Xenotransplanted hMSCs and hCs survived in porcine IVDs for 6 months and produced collagen II in all six animals. Six months after transplantation of cell/gel, pronounced endplate changes indicating severe IVD degeneration were observed at MRI in 1/3 hC/gel, 1/3 hMSCs/gel and 1/3 gel only injected IVDs at MRI and 1/3 hMSC/gel, 3/3 hC/gel, 2/3 gel and 1/3 injured IVDs showed positive staining for bone mineralization. In 1 of 3 discs receiving hC/gel, in 1 of 3 receiving hMSCs/gel, and in 1 of 3 discs receiving gel alone. Injected IVDs on MRI results in 1 of 3 hMSC/gel, in 3 of 3 hC/gel, in 2 of 3 gel, and in 1 of 3 injured IVDs animals showed positive staining for bone mineralization. The investigated hyaluronan gel carrier is not suitable for use in cell therapy of injured/degenerated IVDs. The high cell proliferation observed in vitro in the hyaluronan could have been a negative factor in vivo, since most cell/gel transplanted IVDs showed degenerative changes at MRI and positive bone mineralization staining. However, this xenotransplantation model is valuable for evaluating possible cell therapy strategies for human degenerated IVDs. PMID- 22072599 TI - Problems hearing in noise in older adults: a review of spatial processing disorder. AB - Difficulty understanding speech in background noise, even with amplification to restore audibility, is a common problem for hearing-impaired individuals and is especially frequent in older adults. Despite the debilitating nature of the problem the cause is not yet completely clear. This review considers the role of spatial processing ability in understanding speech in noise, highlights the potential impact of disordered spatial processing, and attempts to establish if aging leads to reduced spatial processing ability. Evidence supporting and opposing the hypothesis that spatial processing is disordered among the aging population is presented. With a few notable exceptions, spatial processing ability was shown to be reduced in an older population in comparison to young adults, leading to poorer speech understanding in noise. However, it is argued that to conclude aging negatively effects spatial processing ability may be oversimplified or even premature given potentially confounding factors such as cognitive ability and hearing impairment. Further research is required to determine the effect of aging and hearing impairment on spatial processing and to investigate possible remediation options for spatial processing disorder. PMID- 22072600 TI - Predicting flexible loop regions that interact with ligands: the challenge of accurate scoring. AB - Flexible loop regions play a critical role in the biological function of many proteins and have been shown to be involved in ligand binding. In the context of structure-based drug design, using or predicting an incorrect loop configuration can be detrimental to the study if the loop is capable of interacting with the ligand. Three protein systems, each with at least one flexible loop region in close proximity to the known binding site, were selected for loop prediction using the CorLps program; a six residue loop region from phosphoribosylglycinamide formyltransferase (GART), two nine residue loop regions from cytochrome P450 (CYP) 119, and an 11 residue loop region from enolase were selected for loop prediction. The results of this study indicate that the statistically based DFIRE scoring function implemented in the CorLps program did not accurately rank native-like predicted loop configurations in any protein system. In an attempt to improve the ranking of the native-like predicted loop configurations, the MM/GBSA and the optimized MM/GBSA-dsr scoring functions were used to re-rank the predicted loops with and without bound ligand. In general, single snapshot MM/GBSA scoring provided the best ranking of native-like loop configurations. Based on the scoring function analyses presented, the optimal ranking of native-like loop configurations is still a difficult challenge and the choice of the "best" scoring function appears to be system dependent. PMID- 22072601 TI - Evaluation of the minimum energy hypothesis and other potential optimality criteria for human running. AB - A popular hypothesis for human running is that gait mechanics and muscular activity are optimized in order to minimize the cost of transport (CoT). Humans running at any particular speed appear to naturally select a stride length that maintains a low CoT when compared with other possible stride lengths. However, it is unknown if the nervous system prioritizes the CoT itself for minimization, or if some other quantity is minimized and a low CoT is a consequential effect. To address this question, we generated predictive computer simulations of running using an anatomically inspired musculoskeletal model and compared the results with data collected from human runners. Three simulations were generated by minimizing the CoT, the total muscle activation or the total muscle stress, respectively. While all the simulations qualitatively resembled real human running, minimizing activation predicted the most realistic joint angles and timing of muscular activity. While minimizing the CoT naturally predicted the lowest CoT, minimizing activation predicted a more realistic CoT in comparison with the experimental mean. The results suggest a potential control strategy centred on muscle activation for economical running. PMID- 22072602 TI - Fitness consequences of plants growing with siblings: reconciling kin selection, niche partitioning and competitive ability. AB - Plant studies that have investigated the fitness consequences of growing with siblings have found conflicting evidence that can support different theoretical frameworks. Depending on whether siblings or strangers have higher fitness in competition, kin selection, niche partitioning and competitive ability have been invoked. Here, we bring together these processes in a conceptual synthesis and argue that they can be co-occurring. We propose that these processes can be reconciled and argue for a trait-based approach of measuring natural selection instead of the fitness-based approach to the study of sibling competition. This review will improve the understanding of how plants interact socially under competitive situations, and provide a framework for future studies. PMID- 22072603 TI - Plant establishment and invasions: an increase in a seed disperser combined with land abandonment causes an invasion of the non-native walnut in Europe. AB - Successful invasive species often are established for a long time period before increasing exponentially in abundance. This lag phase is one of the least understood phenomena of biological invasions. Plant invasions depend on three factors: a seed source, suitable habitat and a seed disperser. The non-native walnut, Juglans regia, has been planted for centuries in Central Europe but, until recently, has not spread beyond planted areas. However, in the past 20 years, we have observed a rapid increase in walnut abundance, specifically in abandoned agricultural fields. The dominant walnut disperser is the rook, Corvus frugilegus. During the past 50 years, rooks have increased in abundance and now commonly inhabit human settlements, where walnut trees are planted. Central Europe has, in the past few decades, experienced large-scale land abandonment. Walnut seeds dispersed into ploughed fields do not survive, but when cached into ploughed and then abandoned fields, they successfully establish. Rooks preferentially cache seeds in ploughed fields. Thus, land-use change combined with disperser changes can cause rapid increase of a non-native species, allowing it to become invasive. This may have cascading effects on the entire ecosystem. Thus, species that are non-native and not invasive can become invasive as habitats and dispersers change. PMID- 22072604 TI - Old World monkeys are more similar to humans than New World monkeys when playing a coordination game. AB - There is much debate about how humans' decision-making compares with that of other primates. One way to explore this is to compare species' performance using identical methodologies in games with strategical interactions. We presented a computerized Assurance Game, which was either functionally simultaneous or sequential, to investigate how humans, rhesus monkeys and capuchin monkeys used information in decision-making. All species coordinated via sequential play on the payoff-dominant Nash equilibrium, indicating that information about the partner's choice improved decisions. Furthermore, some humans and rhesus monkeys found the payoff-dominant Nash equilibrium in the simultaneous game, even when it was the first condition presented. Thus, Old World primates solved the task without any external cues to their partner's choice. Finally, when not explicitly prohibited, humans spontaneously used language to coordinate on the payoff dominant Nash equilibrium, indicating an alternative mechanism for converting a simultaneous move game into a sequential move game. This phylogenetic distribution implies that no single mechanism drives coordination decisions across the primates, while humans' ability to spontaneously use language to change the structure of the game emphasizes that multiple mechanisms may be used even within the same species. These results provide insight into the evolution of decision-making strategies across the primates. PMID- 22072605 TI - Skimming the surface with Burgess Shale arthropod locomotion. AB - The first arthropod trackways are described from the Middle Cambrian Burgess Shale Formation of Canada. Trace fossils, including trackways, provide a rich source of biological and ecological information, including direct evidence of behaviour not commonly available from body fossils alone. The discovery of large arthropod trackways is unique for Burgess Shale-type deposits. Trackway dimensions and the requisite number of limbs are matched with the body plan of a tegopeltid arthropod. Tegopelte, one of the rarest Burgess Shale animals, is over twice the size of all other benthic arthropods known from this locality, and only its sister taxon, Saperion, from the Lower Cambrian Chengjiang biota of China, approaches a similar size. Biomechanical trackway analysis demonstrates that tegopeltids were capable of rapidly skimming across the seafloor and, in conjunction with the identification of gut diverticulae in Tegopelte, supports previous hypotheses on the locomotory capabilities and carnivorous mode of life of such arthropods. The trackways occur in the oldest part (Kicking Horse Shale Member) of the Burgess Shale Formation, which is also known for its scarce assemblage of soft-bodied organisms, and indicate at least intermittent oxygenated bottom waters and low sedimentation rates. PMID- 22072606 TI - The structure of cross-cultural musical diversity. AB - Human cultural traits, such as languages, musics, rituals and material objects, vary widely across cultures. However, the majority of comparative analyses of human cultural diversity focus on between-culture variation without consideration for within-culture variation. In contrast, biological approaches to genetic diversity, such as the analysis of molecular variance (AMOVA) framework, partition genetic diversity into both within- and between-population components. We attempt here for the first time to quantify both components of cultural diversity by applying the AMOVA model to music. By employing this approach with 421 traditional songs from 16 Austronesian-speaking populations, we show that the vast majority of musical variability is due to differences within populations rather than differences between. This demonstrates a striking parallel to the structure of genetic diversity in humans. A neighbour-net analysis of pairwise population musical divergence shows a large amount of reticulation, indicating the pervasive occurrence of borrowing and/or convergent evolution of musical features across populations. PMID- 22072607 TI - Embryonic exposure to corticosterone modifies the juvenile stress response, oxidative stress and telomere length. AB - Early embryonic exposure to maternal glucocorticoids can broadly impact physiology and behaviour across phylogenetically diverse taxa. The transfer of maternal glucocorticoids to offspring may be an inevitable cost associated with poor environmental conditions, or serve as a maternal effect that alters offspring phenotype in preparation for a stressful environment. Regardless, maternal glucocorticoids are likely to have both costs and benefits that are paid and collected over different developmental time periods. We manipulated yolk corticosterone (cort) in domestic chickens (Gallus domesticus) to examine the potential impacts of embryonic exposure to maternal stress on the juvenile stress response and cellular ageing. Here, we report that juveniles exposed to experimentally increased cort in ovo had a protracted decline in cort during the recovery phase of the stress response. All birds, regardless of treatment group, shifted to oxidative stress during an acute stress response. In addition, embryonic exposure to cort resulted in higher levels of reactive oxygen metabolites and an over-representation of short telomeres compared with the control birds. In many species, individuals with higher levels of oxidative stress and shorter telomeres have the poorest survival prospects. Given this, long-term costs of glucocorticoid-induced phenotypes may include accelerated ageing and increased mortality. PMID- 22072608 TI - Novel methods reveal shifts in migration phenology of barn swallows in South Africa. AB - Many migratory bird species, including the barn swallow (Hirundo rustica), have advanced their arrival date at Northern Hemisphere breeding grounds, showing a clear biotic response to recent climate change. Earlier arrival helps maintain their synchrony with earlier springs, but little is known about the associated changes in phenology at their non-breeding grounds. Here, we examine the phenology of barn swallows in South Africa, where a large proportion of the northern European breeding population spends its non-breeding season. Using novel analytical methods based on bird atlas data, we show that swallows first arrive in the northern parts of the country and gradually appear further south. On their north-bound journey, they leave South Africa rapidly, resulting in mean stopover durations of 140 days in the south and 180 days in the north. We found that swallows are now leaving northern parts of South Africa 8 days earlier than they did 20 years ago, and so shortened their stay in areas where they previously stayed the longest. By contrast, they did not shorten their stopover in other parts of South Africa, leading to a more synchronized departure across the country. Departure was related to environmental variability, measured through the Southern Oscillation Index. Our results suggest that these birds gain their extended breeding season in Europe partly by leaving South Africa earlier, and thus add to scarce evidence for phenology shifts in the Southern Hemisphere. PMID- 22072609 TI - Evolution of reproductive life histories in island birds worldwide. AB - Island environments typically share characteristics such as impoverished biotas and less-seasonal climates, which should be conducive to specific adaptations by organisms. However, with the exception of morphological studies, broad-scale tests of patterns of adaptation on islands are rare. Here, I examine reproductive patterns in island birds worldwide. Reproductive life histories are influenced by latitude, which could affect the response to insularity; therefore, I additionally test this hypothesis. Island colonizers showed mostly bi-parental care, but there was a significant increase in cooperative breeding on islands. Additionally, I found support for previous suggestions of reduced fecundity, longer developmental periods and increased investment in young on islands. However, clutch size increased with latitude at a rate nearly five times faster on the mainland than on the islands revealing a substantially stronger effect of insularity at higher latitudes. Latitude and insularity may also interact to determine egg volume and incubation periods, but these effects were less clear. Analyses of reproductive success did not support an effect of reduced nest predation as a driver of reproductive change, but this requires further study. The effect of latitude detected here suggests that the evolutionary changes associated with insularity relate to environmental stability and improved adult survival. PMID- 22072610 TI - Arctic plant diversity in the Early Eocene greenhouse. AB - For the majority of the Early Caenozoic, a remarkable expanse of humid, mesothermal to temperate forests spread across Northern Polar regions that now contain specialized plant and animal communities adapted to life in extreme environments. Little is known on the taxonomic diversity of Arctic floras during greenhouse periods of the Caenozoic. We show for the first time that plant richness in the globally warm Early Eocene (approx. 55-52 Myr) in the Canadian High Arctic (76 degrees N) is comparable with that approximately 3500 km further south at mid-latitudes in the US western interior (44-47 degrees N). Arctic Eocene pollen floras are most comparable in richness with today's forests in the southeastern United States, some 5000 km further south of the Arctic. Nearly half of the Eocene, Arctic plant taxa are endemic and the richness of pollen floras implies significant patchiness to the vegetation type and clear regional richness of angiosperms. The reduced latitudinal diversity gradient in Early Eocene North American plant species demonstrates that extreme photoperiod in the Arctic did not limit taxonomic diversity of plants. PMID- 22072611 TI - Sexual conflict over parental investment in repeated bouts: negotiation reduces overall care. AB - Understanding the evolution of parental care is complicated by the occurrence of evolutionary conflicts of interest within the family, variation in the quality and state of family members, and repeated bouts of investment in a family of offspring. As a result, family members are expected to negotiate over care. We present a model for the resolution of sexual conflict in which parents negotiate over repeated bouts of care. Negotiation is mediated by parents deciding at the start of each bout how much care to give on the basis of the state (mass) of offspring, which reflects the amount of care previously received. The evolutionarily stable pattern of care depends on whether the parents care together for the whole family, or each cares alone for part of the divided family. When they care together, they provide less care in the first bout, more in the last bout, and less care overall, resulting in lower parental and offspring fitness. Our results emphasize that negotiation over parental care may occur as a means of avoiding exploitation owing to sexual conflict, even in the absence of variation in the quality of either sex of parent, and lead to a reduction in fitness. PMID- 22072612 TI - Structural insight into mechanism and diverse substrate selection strategy of L ribulokinase. AB - The araBAD operon encodes three different enzymes required for catabolism of L arabinose, which is one of the most abundant monosaccharides in nature. L ribulokinase, encoded by the araB gene, catalyzes conversion of L-ribulose to L ribulose-5-phosphate, the second step in the catabolic pathway. Unlike other kinases, ribulokinase exhibits diversity in substrate selectivity and catalyzes phosphorylation of all four 2-ketopentose sugars with comparable k(cat) values. To understand ribulokinase recognition and phosphorylation of a diverse set of substrates, we have determined the X-ray structure of ribulokinase from Bacillus halodurans bound to L-ribulose and investigated its substrate and ATP co-factor binding properties. The polypeptide chain is folded into two domains, one small and the other large, with a deep cleft in between. By analogy with related sugar kinases, we identified (447)GGLPQK(452) as the ATP-binding motif within the smaller domain. L-ribulose binds in the cleft between the two domains via hydrogen bonds with the side chains of highly conserved Trp126, Lys208, Asp274, and Glu329 and the main chain nitrogen of Ala96. The interaction of L ribulokinase with L-ribulose reveals versatile structural features that help explain recognition of various 2-ketopentose substrates and competitive inhibition by L-erythrulose. Comparison of our structure to that of the structures of other sugar kinases revealed conformational variations that suggest domain-domain closure movements are responsible for establishing the observed active site environment. PMID- 22072613 TI - RhoA/ROCK may involve in cardiac hypertrophy induced by experimental hyperthyroidism. AB - In this study, the role of the RhoA/Rho-kinase (RhoA/ROCK)-signaling pathway in cardiovascular dysfunction associated with hyperthyroidism was examined with the use of fasudil, a Rho-kinase inhibitor. Male Spraque-Dawley rats were treated with l-thyroxine (T(4)) alone, T(4) + low-dose fasudil (2 mg/kg/day) or T(4) + high-dose fasudil (10 mg/kg/day) and compared with control animals. Rats in the T(4) group showed an increase in the ratio of heart weight to body weight, which was ameliorated by fasudil at both low and high doses. Morphometric and hemodynamic parameters were also evaluated and confirmed that fasudil attenuated the cardiac hypertrophy induced by T(4). The extent of phosphorylation of the myosin phosphatase targeting subunit was quantified by Western blotting to evaluate the activity of Rho-kinase in the heart tissue. Both Western blotting and reverse transcriptase-polymerase chain reaction analyses revealed enhancement of Rho-kinase and activator protein 1 activity and reduction of c-FLIP(L) expression in the T(4) group, and this response was inhibited by fasudil in a dose-dependent manner. Furthermore, fasudil inhibited apoptosis induced by T(4) as evidenced by the detection of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and the expressions of bax and bcl-2. These results suggested that the RhoA/ROCK pathway is involved in the cardiac hypertrophy induced by experimental hyperthyroidism. The antagonism of this pathway may thus be useful as an alternative target in the treatment of hyperthyroid heart disease. PMID- 22072614 TI - Regulation of pancreatic cancer by neuropsychological stress responses: a novel target for intervention. AB - Pancreatic cancer has a poor prognosis and is associated with high levels of psychological stress that may adversely affect clinical outcomes. However, the potential influence of neuropsychological factors on pancreatic cancer has not been investigated to date. Using a mouse model of social stress, we have tested the hypothesis that psychological stress promotes the progression of pancreatic cancer xenografts via neurotransmitter-induced activation of multiple pathways and that the inhibitory neurotransmitter gamma-aminobutiric acid (GABA) inhibits these responses. Sytemic and xenograft levels of noradrenalin, adrenalin, GABA, cortisol, vascular endothelial growth factor (VEGF) and cyclic adenosine 3', 5' monophosphate (cAMP) were measured by immunoassays. Xenograft expression of nicotinic acetylcholine receptors (nAChRs) alpha3, alpha4, alpha5, alpha6 and alpha7 and beta-adrenergic receptors 1 and 2 were assessed by real-time PCR and western blots. Expression of glutamate decarboxylases GAD65 and GAD67 and phosphorylated and unphosphorylated signaling proteins of relevance to pancreatic cancer were determined in tumor tissue by western blots. Psychological stress significantly promoted xenograft growth and increased systemic and tumor levels of noradrenalin, adrenalin, cortisol, VEGF and cAMP while GABA and GAD were suppressed. Stress upregulated nAChR proteins but not RNAs and induced phosphorylated ERK, CREB, Src and AKT in xenografts. Reduction of cAMP by treatment with GABA prevented tumor progression and activation of signaling proteins. Our findings suggest that neurotransmitter responses to psychological stress negatively impact clinical outcomes of pancreatic cancer via the activation of multiple pathways and that replacement of the suppressed inhibitory neurotransmitter GABA prevents these effects. PMID- 22072615 TI - microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl 2. AB - Deregulated microRNAs participate in carcinogenesis and cancer progression, but their roles in cancer development remain unclear. In this study, miR-365 expression was found to be downregulated in human colon cancer tissues as compared with that in matched non-neoplastic mucosa tissues, and its downregulation was correlated with cancer progression and poor survival in colon cancer patients. Functional studies revealed that restoration of miR-365 expression inhibited cell cycle progression, promoted 5-fluorouracil-induced apoptosis and repressed tumorigenicity in colon cancer cell lines. Furthermore, bioinformatic prediction and experimental validation were used to identify miR 365 target genes and indicated that the antitumor effects of miR-365 were probably mediated by its targeting and repression of Cyclin D1 and Bcl-2 expression, thus inhibiting cell cycle progression and promoting apoptosis. These results suggest that downregulation of miR-365 in colon cancer may have potential applications in prognosis prediction and gene therapy in colon cancer patients. PMID- 22072617 TI - Cell signaling pathways associated with a reduction in mammary cancer burden by dietary common bean (Phaseolus vulgaris L.). AB - Emerging evidence indicates that common bean (Phaseolus vulgaris L.) is associated with reduced cancer risk in human populations and rodent carcinogenesis models. This study sought to identify cancer-associated molecular targets that mediate the effects of bean on cancer burden in a chemically induced rat model for breast cancer. Initial experiments were conducted using a high dietary concentration of bean (60% wt/wt) where carcinoma burden in bean-fed rats was reduced 62.2% (P < 0.001) and histological and western blot analyses revealed that the dominant cellular process associated with reduced burden was induction of apoptosis. Further analysis of mammary carcinomas revealed changes in the phosphorylation states of mammalian target of rapamycin (mTOR) substrates (4E binding protein 1 and p70S6 kinase) and mTOR regulators adenosine monophosphate activated protein kinase and protein kinase B (Akt) (P < 0.001). Effects on mTOR signaling in carcinomas were also found at lower dietary concentrations of bean (7.5-30% wt/wt). Liquid chromatography-time of flight-mass spectrometry analysis of plasma provided evidence of altered lipid metabolism consistent with reduced mTOR network activity in the liver (P < 0.001). Plasma concentrations of insulin and insulin-like growth factor-1 were reduced by 36.3 and 38.9%, respectively, (P < 0.001), identifying a link to Akt regulation. Plasma C-reactive protein, a prognostic marker for long-term survival in breast cancer patients, was reduced by 23% (P < 0.001) in bean-fed rats. Identification of a role for the mTOR signaling network in the reduction of cancer burden by dietary bean is highly relevant given that this pathway is deregulated in the majority of human breast cancers. PMID- 22072616 TI - DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 4 aminobiphenyl are infrequently detected in human mammary tissue by liquid chromatography/tandem mass spectrometry. AB - Some epidemiological investigations have revealed that frequent consumption of well-done cooked meats and tobacco smoking are risk factors for breast cancer in women. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic aromatic amine that is formed in well-done cooked meat, and 4-aminobiphenyl (4 ABP) is an aromatic amine that arises in tobacco smoke and occurs as a contaminant in the atmosphere. Both compounds are rodent mammary carcinogens, and putative DNA adducts of PhIP and 4-ABP have been frequently detected, by immunohistochemistry (IHC) or (32)P-post-labeling methods, in mammary tissue of USA women. Because of these findings, PhIP and 4-ABP have been implicated as causal agents of human breast cancer. However, the biomarker data are controversial: both IHC and (32)P-post-labeling are non-selective screening methods and fail to provide confirmatory spectral data. Consequently, the identities of the lesions are equivocal. We employed a specific and sensitive liquid chromatography/mass spectrometry (MS) method, to screen tumor-adjacent normal mammary tissue for DNA adducts of PhIP and 4-ABP. Only 1 of 70 biopsy samples obtained from Minneapolis, Minnesota breast cancer patients contained a PhIP-DNA adduct. The level was three adducts per 10(9) nucleotides, a level that is 100-fold lower than the mean level of PhIP adducts reported by IHC or (32)P post-labeling methods. The occurrence of 4-ABP-DNA adducts was nil in those same breast tissues. Our findings, derived from a specific mass spectrometry method, signify that PhIP and 4-ABP are not major DNA-damaging agents in mammary tissue of USA women and raise questions about the roles of these chemicals in breast cancer. PMID- 22072618 TI - Functional FEN1 genetic variants contribute to risk of hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer. AB - As a DNA repair protein, Flap endonuclease 1 (FEN1) plays crucial parts in preventing carcinogenesis. Two functional germ line variants (-69G > A and 4150G > T) in the FEN1 gene have been associated with DNA damage levels in coke oven workers and lung cancer risk in general populations. However, the role of these genetic variants on gastrointestinal cancer susceptibility is unknown. Therefore, we evaluated the association between these polymorphisms and gastrointestinal cancer risk in two independent case-control cohorts consisted of a total of 1850 gastrointestinal cancer (hepatocellular carcinoma, esophageal cancer, gastric cancer and colorectal cancer) patients and 2222 healthy controls. The impact of these variations on FEN1 expression was also examined using liver, esophagus, stomach and colon normal tissues. It was found that the FEN1 -69GG genotypes were significantly correlated to increased risk for developing gastrointestinal cancer compared with the -69AA genotype in both cohorts [Jinan cohort: odds ratios (OR) = 2.14, 95% confidence interval (CI) = 1.47-2.80, P = 1.0 * 10(-)(6); Huaian cohort: OR = 1.93, 95% CI = 1.37-2.50, P = 0.5 * 10(-6)]. Similar results were observed for 4150G > T polymorphism. In the combined meta-analyses, OR for -69GG or 4150GG genotype was 2.02 (95% CI = 1.59-2.45) or 1.86 (95% CI = 1.45-2.28) compared with -69AA or 4150TT genotype. In vivo FEN1 messenger RNA expression analyses showed that the -69G or 4150G allele carriers had ~2-fold decreased FEN1 expression in gastrointestinal tissues compared with -69A or 4150T carriers, indicating that lower FEN1 expression may lead to higher risk for malignant transformation of gastrointestinal cells. Our results highlight FEN1 as an important gene in human gastrointestinal oncogenesis and genetic polymorphisms in FEN1 confer susceptibility to gastrointestinal cancers. PMID- 22072619 TI - Telomere length variation in normal epithelial cells adjacent to tumor: potential biomarker for breast cancer local recurrence. AB - A better understanding of the risk of local recurrence (LR) will facilitate therapeutic decision making in the management of early breast cancers. In the present study, we investigated whether telomere length in the normal breast epithelial cells surrounding the tumor is predictive of breast cancer LR; 152 women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this nested case-control study. Cases (patients had LR) and controls (patients had no LR) were matched on year of surgery, age at diagnosis and type of surgery. Telomere fluorescent in situ hybridization was used to determine the telomere length using formalin fixed paraffin-embedded breast tissues. Small telomere length variation (TLV), defined as the coefficient variation of telomere lengths among examined cells, in normal epithelial cells adjacent to the tumor was significantly associated with a 5-fold (95% confidence interval = 1.2-22.2) increased risk of breast cancer LR. When the subjects were categorized into quartiles, a significant inverse dose-response relationship was observed with lowest versus highest quartile odds ratio of 15.3 (P(trend) = 0.012). Patients who had large TLV had significantly better 10 year recurrence free survival rate compared with patients who had small TLV (80 versus 33%). The present study revealed that TLV in normal epithelial cells adjacent to tumor is a strong predictor of breast cancer LR. If confirmed by future studies, TLV in normal epithelial cells adjacent to tumor has the potential to become a promising biomarker for predicting breast cancer LR after breast conserving surgery. PMID- 22072620 TI - Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), isolated from Plumbago zeylanica, inhibits ultraviolet radiation-induced development of squamous cell carcinomas. AB - Plumbagin (PL) (5-hydroxy-2-methyl-1,4-napthoquinone), a medicinal plant-derived naphthoquinone, was isolated from the roots of the Plumbago zeylanica L. (also known as Chitrak). The roots of P. zeylanica L. have been used in Indian medicine for >2500 years as an anti-atherogenic, cardiotonic, hepatoprotective and neuroprotective agent. We present here that topical application of non-toxic doses (100-500 nmol) of PL to skin elicits dose-dependent inhibition of ultraviolet radiation (UVR)-induced development of squamous cell carcinomas (SCC). In this experiment, FVB/N mice were exposed to UVR (2 kJ/m(2)) three times weekly from a bank of six Kodacel-filtered FS40 sunlamps (~ 60% UVB and 40% UVA). Carcinoma incidence in mice treated with vehicle, 100, 200 or 500 nmol PL, at 44 weeks post-UVR, were 86, 80 (P = 0.67), 53 (P = 0.12) and 7% (P = 0.0075), respectively. Both vehicle and PL-treated mice gained weight and did not exhibit any signs of toxicity during the entire period of the experiment. Molecular mechanisms associated with inhibition of UVR-induced development of SCC involved induction of apoptosis and inhibition of cell proliferation. Specific findings are that PL treatment (i) inhibited UVR-induced DNA binding of activating protein 1, nuclear factor-kappaB, Stat3 transcription factors and Stat3-regulated molecules (cdc25A and Survivin); (ii) inhibited protein levels of pERK1/2, PI3K85, pAKTSer473, Bcl(2), BclxL, proliferating cell nuclear antigen and cell cycle inhibitory proteins p27 and p21 and (iii) increased UVR-induced Fas associated death domain expression, poly (ADP-ribose) polymerase protein cleavage and Bax/Bcl(2) ratio. Taken together, our findings suggest that PL may be a novel agent for the prevention of skin cancer. PMID- 22072621 TI - Induction of NAD(P)H-quinone oxidoreductase 1 by antioxidants in female ACI rats is associated with decrease in oxidative DNA damage and inhibition of estrogen induced breast cancer. AB - Exact mechanisms underlying the initiation and progression of estrogen-related cancers are not clear. Literature, evidence and our studies strongly support the role of estrogen metabolism-mediated oxidative stress in estrogen-induced breast carcinogenesis. We have recently demonstrated that antioxidants vitamin C and butylated hydroxyanisole (BHA) or estrogen metabolism inhibitor alpha naphthoflavone (ANF) inhibit 17beta-estradiol (E2)-induced mammary tumorigenesis in female ACI rats. The objective of the current study was to identify the mechanism of antioxidant-mediated protection against E2-induced DNA damage and mammary tumorigenesis. Female ACI rats were treated with E2 in the presence or absence of vitamin C or BHA or ANF for up to 240 days. Nuclear factor erythroid 2 related factor 2 (NRF2) and NAD(P)H-quinone oxidoreductase 1 (NQO1) were suppressed in E2-exposed mammary tissue and in mammary tumors after treatment of rats with E2 for 240 days. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. Time course studies indicate that NQO1 levels tend to increase after 4 months of E2 treatment but decrease on chronic exposure to E2 for 8 months. Vitamin C and BHA significantly increased NQO1 levels after 120 days. 8-Hydroxydeoxyguanosine (8-OHdG) levels were higher in E2-exposed mammary tissue and in mammary tumors compared with age-matched controls. Vitamin C or BHA treatment significantly decreased E2-mediated increase in 8-OHdG levels in the mammary tissue. In vitro studies using silencer RNA confirmed the role of NQO1 in prevention of oxidative DNA damage. Our studies further demonstrate that NQO1 upregulation by antioxidants is mediated through NRF2. PMID- 22072622 TI - MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFbetaR2) in colon cancer cells. AB - Although microRNA-21 (miR-21) is emerging as an oncogene and has been shown to target several tumor suppressor genes, including programmed cell death 4 (PDCD4), its precise mechanism of action on cancer stem cells (CSCs) is unclear. Herein, we report that FOLFOX-resistant HCT-116 and HT-29 cells that are enriched in CSCs show a 3- to 7-fold upregulation of pre- and mature miR-21 and downregulation of PDCD4. Likewise, overexpression of miR-21 in HCT-116 cells, achieved through stable transfection, led to the downregulation of PDCD4 and transforming growth factor beta receptor 2 (TGFbetaR2). In contrast, the levels of beta-catenin, TCF/LEF activity and the expression of c-Myc, Cyclin-D, which are increased in CSCs, are also augmented in miR-21 overexpressing colon cancer cells, accompanied by an increased sphere forming ability in vitro and tumor formation in SCID mice. Downregulation of TGFbetaR2 could be attributed to decreased expression of the receptor as evidenced by reduction in the activity of the luciferase gene construct comprising TGFbetaR2-3' untranslated region (UTR) sequence that binds to miR-21. Moreover, we observed that downregulation of miR-21 enhances luciferase-TGFbetaR2-3' UTR activity suggesting TGFbetaR2 as being one of the direct targets of miR-21. Further support is provided by the observation that transfection of TGFbetaR2 in HCT-116 cells attenuates TCF/LEF luciferase activity, accompanied by decreased expression of beta-catenin, c-Myc and Cyclin D1. Our current data suggest that miR-21 plays an important role in regulating stemness by modulating TGFbetaR2 signaling in colon cancer cells. PMID- 22072623 TI - Allosteric regulation of PKCtheta: understanding multistep phosphorylation and priming by ligands in AGC kinases. AB - Protein kinases play critical roles in cellular activation and differentiation, and are involved in numerous pathophysiological processes. As a critical component of the regulatory circuitry of the cell, the kinase domain has the ability to integrate multiple signals, yielding a predetermined output. In PKC and other protein kinases of the AGC family, several phosphorylation sites control the activity, but these are in turn influenced by the presence of ligands in the binding pocket, which promotes phosphorylation. Here, we take PKC-theta as a prototypical member of the family and use molecular dynamics simulations to investigate the cross-talk that exists between regulatory and functional sites. We first show how the apo-unphosphorylated form of the kinase is populating a conformational space in which access to the ATP binding site and to the activation loop (AL) are simultaneously hindered. This could explain why the inactive state is not only catalytically incompetent but also resistant to activation. AL phosphorylation induces ATP binding site opening, which can then readily accept the cofactor. But the signal transmission mechanism works both ways, and if ligand binding to the unphosphorylated form occurs first, the AL is de-protected and becomes exposed to phosphorylation, thus providing an explanation for the paradoxical activation of PKCs by their inhibitors. PMID- 22072624 TI - Physiological and behavioural stress responses in cynomolgus macaques (Macaca fascicularis) to noise associated with construction work. AB - The aim of the present study was to evaluate the behavioural and physiological responses to environmental disturbances (live and recorded dynamite explosions) in laboratory non-human primates in preparation for a future tunnel construction underneath our animal facility. In a pilot study (A) on 20 female Macaca fascicularis, a day of test blasts resulted in an increase in faecal cortisol and immunoreactive cortisol metabolites (CICM), and the animals reacted behaviourally with vertical flight and vocalizations. In a follow-up study (B), we assessed the impact of 10 days of exposure to recorded detonations on the behaviour and CICM in 16 M. fascicularis. In the latter study we introduced a predictive signal, serving as a conditional stimulus, to half of the animals. We found no significant effects of the noise in the Signal group; while the Control groups' CICM values were affected. The behaviour was largely unaffected in the two groups. It was decided not to introduce a research moratorium on biomedical research planned to be conducted during the future tunnel construction, and that a conditional stimulus ('warning signal') will be used. PMID- 22072625 TI - Severe hypoxaemia with a left ventricular assist device in a minipig model with an undiagnosed congenital cardiac disease. AB - We describe the placement of a left ventricular assist device (LVAD) in a pig with spontaneously occurring atrial septal defect (ASD) (incidental finding) that created a right-left cardiac shunt, with subsequent severe hypoxaemia. Early diagnosis was critical in order to prevent end-organ damage due to hypoxaemia. Adequate monitoring alerted us to the deterioration in oxygenation, haemodynamics and cerebral oxygen metabolism. This forced us to change the level of assistance provided by the pump, and thus dramatically correct this impairment. Necropsy revealed an ostium secundum ASD. In conclusion, if hypoxaemia presents after implementation of an LVAD, the presence of a right-left shunt must be ruled out. The first step must be a judicious reduction in assist device flow to minimize intracardiac shunting. Subsequently, atrial septal closure of the defect should be considered. We report an experimental model of severe hypoxaemia after placement of an LVAD as part of a larger research project. PMID- 22072626 TI - Computational studies of LXR molecular interactions reveal an allosteric communication pathway. AB - The liver X receptor, LXRalpha, is an important regulator of genes involved in metabolism and inflammation. The mechanism of communication between the cofactor peptide and the ligand in the ligand-binding pocket is a crucial and often discussed issue for the nuclear receptors (NRs), but such allosteric signaling pathways are difficult to detect and the transmission mechanism remains elusive. Here, we apply the anisotropic thermal diffusion method to the LXRalpha with bound coactivator and ligand. We detected a possible communication pathway between the coactivator peptide and the ligand. The signal is transmitted both through the receptor backbone and side chains. A key signaling residue is the first leucine in the cofactor peptide recognition motif LXXLL, which is conserved within the NR cofactors, suggesting a general mechanism for allosteric signaling. Furthermore, we studied the LXR receptor and cofactor molecular interactions in detail using molecular dynamics simulations. The protein-protein interaction patterns in the complexes of nine different cofactor peptides and holo-LXRalpha were characterized, revealing the importance of the receptor-cofactor charge clamp interaction. Specific, but infrequently occurring interactions were observed toward the cofactor peptide C-terminal residues. Thus, additional specificity between LXRalpha and its cofactors is likely to be found in molecular interactions outside the cofactor peptide or in other biological factors. PMID- 22072627 TI - Minimally invasive childhood and adult circumcision. AB - Using the Gomco circumcision clamp and sealing the wound with tissue adhesive results in a minimally invasive circumcision suitable for all age groups beyond the neonatal period. It is easy to perform and can be performed by generalists with local anaesthetic and standard instruments. PMID- 22072628 TI - Structural characterization by nuclear magnetic resonance of the impact of phosphorylation in the proline-rich region of the disordered Tau protein. AB - Phosphorylation of the neuronal Tau protein is implicated in both the regulation of its physiological function of microtubule stabilization and its pathological propensity to aggregate into the fibers that characterize Alzheimer's diseased neurons. However, how specific phosphorylation events influence both aspects of Tau biology remains largely unknown. In this study, we address the structural impact of phosphorylation of the Tau protein by Nuclear Magnetic Resonance (NMR) spectroscopy on a functional fragment of Tau (Tau[Ser208-Ser324] = TauF4). TauF4 was phosphorylated by the proline-directed CDK2/CycA3 kinase on Thr231 (generating the AT180 epitope), Ser235, and equally on Thr212 and Thr217 in the Proline-rich region (Tau[Ser208-Gln244] or PRR). These modifications strongly decrease the capacity of TauF4 to polymerize tubulin into microtubules. While all the NMR parameters are consistent with a globally disordered Tau protein fragment, local clusters of structuration can be defined. The most salient result of our NMR analysis is that phosphorylation in the PRR stabilizes a short alpha helix that runs from pSer235 till the very beginning of the microtubule-binding region (Tau[Thr245-Ser324] or MTBR of TauF4). Phosphorylation of Thr231/Ser235 creates a N-cap with helix stabilizing role while phosphorylation of Thr212/Thr217 does not induce modification of the local transient secondary structure, showing that the stabilizing effect is sequence specific. Using paramagnetic relaxation experiments, we additionally show a transient interaction between the PRR and the MTBR, observed in both TauF4 and phospho-TauF4. PMID- 22072629 TI - Modulated nicking endonuclease function by the N-terminal extended region of the smr domain in human Bcl-3 binding protein. PMID- 22072630 TI - Roles of human sulfotransferases in genotoxicity of carcinogens using genetically engineered umu test strains. AB - Human sulfotransferase (SULT) 1A1, 1A2, and 1A3 cDNA genes were subcloned separately into the pTrc99A(KM) vector. The generated plasmids were introduced into the Salmonella typhimurium O-acetyltransferase-deficient strain NM6000 (TA1538/1,8-DNP/pSK1002), resulting in the new strains NM7001, NM7002, and NM7003. We compared the sensitivities of these three strains with the parental strain NM7000 against 51 chemicals including aromatic amines, nitroarenes, alkenylbenzenes, estrogens-like chemicals, and other compounds with and without S9 mix by making use of the umu test system that is based on the bacterial SOS induction. 2-Amino-6-methyl-dipyrido[1,2-alpha:3',2'-d]imidazole, 3-methoxy-4 aminoazobenzene, 3-nitrobenzanthrone, 5-nitroacenaphthene, and 3,9 dinitrofluoranthene caused high genotoxicity in the NM7001 strain. The genotoxic effects of 2-aminofluorene, 2-acetylaminofluorene, 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine, 2-nitrofluorene, 1-nitropyrene, and 2-nitropropane were stronger in the NM7002 strain compared with the NM7001 and NM7003 strains. Among the tested benzylic and allylic compounds, 1-hydroxymethylpyrene was detected in the NM7001 strain with the highest sensitivity. Estragole and 1' hydroxysafrole exhibited strong genotoxicity in the NM7003 strain. The estrogen like chemicals such as bisphenol A, genistein, p,n-nonylphenol, and 4 hydroxytamoxifen were not detected as genotoxins in any strain used. Collectively, the present results suggest that the generated test strains are valuable tools in order to elucidate the role of SULT enzymes in the bioactivation of chemicals to environmental carcinogens. PMID- 22072632 TI - Novel techniques and targets in cardiovascular microRNA research. AB - MicroRNAs (miRNAs) are highly conserved, tiny (~22 nucleotides) non-coding RNAs that have emerged as potent regulators of mRNA translation. miRNAs exhibit fine tuning of the control of proteins involved in cell signalling (AE) pathways and in vital cellular and developmental processes. miRNAs are expressed in cardiovascular tissues, and multiple functional aspects of miRNAs underscore their key role in cardiovascular (patho)physiology. The development and increasing use of novel molecular biology tools have contributed to the recent success in miRNA research. In the present review, we discuss current updates on important and novel miRNA techniques, including: (i) miRNA screening tools; (ii) bioanalytical target prediction tools; (iii) target validation tools; and (iv) manipulative miRNA expression tools. We also present an update about recently identified miRNA targets that play a key role in cardiovascular development and disorders. PMID- 22072631 TI - N-terminal domain of soluble epoxide hydrolase negatively regulates the VEGF mediated activation of endothelial nitric oxide synthase. AB - AIMS: The mammalian soluble epoxide hydrolase (sEH) has both an epoxide hydrolase and a phosphatase domain. The role of sEH hydrolase activity in the metabolism of epoxyeicosatrienoic acids (EETs) and the activation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) has been well defined. However, far less is known about the role of sEH phosphatase activity in eNOS activation. In the present study, we investigated whether the phosphatase domain of sEH was involved in the eNOS activation in ECs. METHODS AND RESULTS: The level of eNOS phosphorylation in aortas is higher in the sEH knockout (sEH(-/-)) mice than in wild-type mice. In ECs, pharmacological inhibition of sEH phosphatase or overexpressing sEH with an inactive phosphatase domain enhanced vascular endothelial growth factor (VEGF)-induced NO production and eNOS phosphorylation. In contrast, overexpressing the phosphatase domain of sEH prevented the VEGF mediated NO production and eNOS phosphorylation at Ser617, Ser635, and Ser1179. Additionally, treatment with VEGF induced a c-Src kinase-dependent increase in transient tyrosine phosphorylation of sEH and the formation of a sEH-eNOS complex, which was abolished by treatment with a c-Src kinase inhibitor, PP1, or the c-Src dominant-negative mutant K298M. We also demonstrated that the phosphatase domain of sEH played a key role in VEGF-induced angiogenesis by detecting the tube formation in ECs and neovascularization in Matrigel plugs in mice. CONCLUSION: In addition to epoxide hydrolase activity, phosphatase activity of sEH plays a pivotal role in the regulation of eNOS activity and NO-mediated EC functions. PMID- 22072633 TI - Conduction block in micropatterned cardiomyocyte cultures replicating the structure of ventricular cross-sections. AB - AIMS: Structural and functional heterogeneities in cardiac tissue have been implicated in conduction block and arrhythmogenesis. However, the propensity of specific sites within the heart to initiate conduction block has not been systematically explored. We utilized cardiomyocyte cultures replicating the realistic, magnetic resonance imaging-measured tissue boundaries and fibre directions of ventricular cross-sections to investigate their roles in the development of conduction block. METHODS AND RESULTS: The Sprague-Dawley neonatal rat cardiomyocytes were micropatterned to obtain cultures with realistic ventricular tissue boundaries and either random or realistic fibre directions. Rapid pacing was applied at multiple sites, with action potential propagation optically mapped. Excitation either failed at the stimulus site or conduction block developed remotely, often initiating reentry. The incidence of conduction block in isotropic monolayers (0% of cultures) increased with the inclusion of realistic tissue boundaries (17%) and further with realistic fibre directions (34%). Conduction block incidence was stimulus site-dependent and highest (77%) with rapid pacing from the right ventricular (RV) free wall. Furthermore, conduction block occurred exclusively at the insertion of the RV free wall into the septum, where structure-mediated current source-load mismatches acutely reduced wavefront and waveback velocity. Tissue boundaries and sharp gradients in fibre direction uniquely determined the evolution, shape, and position of conduction block lines. CONCLUSION: Our study suggests that specific micro- and macrostructural features of the ventricle determine the incidence and spatiotemporal characteristics of conduction block, independent of spatial heterogeneities in ion channel expression. PMID- 22072634 TI - The mPTP and its regulatory proteins: final common targets of signalling pathways for protection against necrosis. AB - The mitochondrial permeability transition pore (mPTP) is a non-selective, large conductance channel that is closed under physiological conditions. Opening of the mPTP, leading to abolition of mitochondrial functions, is a major mechanism of myocyte necrosis by ischaemia/reperfusion, and direct inhibition of mPTP opening by use of pharmacological or genetic manipulations limits infarct size in vivo. Multiple pro-survival signal pathways commonly target the mPTP and inhibit its opening. Although the molecular structure of the mPTP has not been established, recent studies have characterized roles of each mPTP subunit and functions of several proteins directly interacting with the mPTP. This article briefly describes the understanding of mPTP regulation and interaction of the mPTP with four proteins (hexokinase II, glycogen synthase kinase-3beta, signal transducer and activator of transcription 3, and sirtuin 3) that are downstream of signal pathways relevant to protection from ischaemia/reperfusion injury. PMID- 22072635 TI - C-path: a Watson-like visit to the pathology lab. AB - Computer-based quantification of tumor morphology has arguably solved the problem of standardized tumor grading (Beck et al., this issue). PMID- 22072636 TI - Harmonization of immune biomarker assays for clinical studies. AB - Assays that measure a patient's immune response play an increasingly important role in the development of immunotherapies. The inherent complexity of these assays and independent protocol development between laboratories result in high data variability and poor reproducibility. Quality control through harmonization- based on integration of laboratory-specific protocols with standard operating procedures and assay performance benchmarks--is one way to overcome these limitations. Harmonization guidelines can be widely implemented to address assay performance variables. This process enables objective interpretation and comparison of data across clinical trial sites and also facilitates the identification of relevant immune biomarkers, guiding the development of new therapies. PMID- 22072637 TI - A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. AB - Obesity, defined as body mass index greater than 30, is a leading cause of morbidity and mortality and a financial burden worldwide. Despite significant efforts in the past decade, very few drugs have been successfully developed for the treatment of obese patients. Biological differences between rodents and primates are a major hurdle for translation of anti-obesity strategies either discovered or developed in rodents into effective human therapeutics. Here, we evaluate the ligand-directed peptidomimetic CKGGRAKDC-GG-(D)(KLAKLAK)(2) (henceforth termed adipotide) in obese Old World monkeys. Treatment with adipotide induced targeted apoptosis within blood vessels of white adipose tissue and resulted in rapid weight loss and improved insulin resistance in obese monkeys. Magnetic resonance imaging and dual-energy x-ray absorptiometry confirmed a marked reduction in white adipose tissue. At experimentally determined optimal doses, monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function. Together, these data in primates establish adipotide as a prototype in a new class of candidate drugs that may be useful for treating obesity in humans. PMID- 22072638 TI - Systematic analysis of breast cancer morphology uncovers stromal features associated with survival. AB - The morphological interpretation of histologic sections forms the basis of diagnosis and prognostication for cancer. In the diagnosis of carcinomas, pathologists perform a semiquantitative analysis of a small set of morphological features to determine the cancer's histologic grade. Physicians use histologic grade to inform their assessment of a carcinoma's aggressiveness and a patient's prognosis. Nevertheless, the determination of grade in breast cancer examines only a small set of morphological features of breast cancer epithelial cells, which has been largely unchanged since the 1920s. A comprehensive analysis of automatically quantitated morphological features could identify characteristics of prognostic relevance and provide an accurate and reproducible means for assessing prognosis from microscopic image data. We developed the C-Path (Computational Pathologist) system to measure a rich quantitative feature set from the breast cancer epithelium and stroma (6642 features), including both standard morphometric descriptors of image objects and higher-level contextual, relational, and global image features. These measurements were used to construct a prognostic model. We applied the C-Path system to microscopic images from two independent cohorts of breast cancer patients [from the Netherlands Cancer Institute (NKI) cohort, n = 248, and the Vancouver General Hospital (VGH) cohort, n = 328]. The prognostic model score generated by our system was strongly associated with overall survival in both the NKI and the VGH cohorts (both log rank P <= 0.001). This association was independent of clinical, pathological, and molecular factors. Three stromal features were significantly associated with survival, and this association was stronger than the association of survival with epithelial characteristics in the model. These findings implicate stromal morphologic structure as a previously unrecognized prognostic determinant for breast cancer. PMID- 22072640 TI - Predictive factors of hospice use among Blacks: applying Andersen's Behavioral Model. AB - The purpose of this prospective, correlational study was to examine the differential ability of demographic variables, beliefs, and values about end-of life, spirituality, and social relationships to predict hospice use among blacks. The framework for this study was the Behavioral Model of Health Services Use. Data were collected from 104 terminally ill black men and women recruited from 6 inpatient and outpatient settings. Only 34% of the individuals participated in hospice services. Chi-square, sequential, and stepwise logistic regressions revealed that the best predictive model consisted of presence of a caregiver, having a religious affiliation, and male gender. Together these factors predicted 13.7% to 19% of hospice use among blacks. Health care providers can use these findings in planning care for patients early in their disease trajectory. PMID- 22072641 TI - CYP8A1 gene polymorphisms and left main coronary artery disease. AB - BACKGROUND: Left main (LM) disease is rare but the most hazardous phenotype of coronary artery disease (CAD). Thus, early detection of participants at high risk of developing left main coronary heart disease (LM-CAD) is crucial. The aim of this study was to identify gene polymorphisms which could distinguish participants who are at high risk of developing LM-CAD. Such a candidate can be the prostaglandin I(2) or prostacyclin (PGI(2)) gene. METHODS: The DNA of 254 participants (151 participants with angiographically documented LM-CAD and 103 healthy controls) was analyzed for the frequency of C1117A polymorphism in the gene coding CYP8A1. RESULTS: The genotype distribution was different between the LM-CAD and the control group. Particularly, the CC genotype of CYP8A1 was commoner in the LM-CAD than in the healthy group (P < .001). Allele frequencies were also differently distributed between the 2 groups. C allele frequency was higher in LM-CAD group (P = .016). CONCLUSIONS: The CC genotype of C1117A polymorphism is associated with higher risk of LM-CAD, which prospectively may have potential importance in screening high-risk populations. However, further investigations in larger populations are required to confirm these findings. PMID- 22072639 TI - Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. AB - Activating mutations in the anaplastic lymphoma kinase (ALK) gene were recently discovered in neuroblastoma, a cancer of the developing autonomic nervous system that is the most commonly diagnosed malignancy in the first year of life. The most frequent ALK mutations in neuroblastoma cause amino acid substitutions (F1174L and R1275Q) in the intracellular tyrosine kinase domain of the intact ALK receptor. Identification of ALK as an oncogenic driver in neuroblastoma suggests that crizotinib (PF-02341066), a dual-specific inhibitor of the ALK and Met tyrosine kinases, will be useful in treating this malignancy. Here, we assessed the ability of crizotinib to inhibit proliferation of neuroblastoma cell lines and xenografts expressing mutated or wild-type ALK. Crizotinib inhibited proliferation of cell lines expressing either R1275Q-mutated ALK or amplified wild-type ALK. In contrast, cell lines harboring F1174L-mutated ALK were relatively resistant to crizotinib. Biochemical analyses revealed that this reduced susceptibility of F1174L-mutated ALK to crizotinib inhibition resulted from an increased adenosine triphosphate-binding affinity (as also seen in acquired resistance to epidermal growth factor receptor inhibitors). Thus, this effect should be surmountable with higher doses of crizotinib and/or with higher affinity inhibitors. PMID- 22072642 TI - Moderate intensities of leisure-time physical activity are associated with lower levels of high-sensitivity C-reactive protein in healthy middle-aged men. AB - Circulating C-reactive protein (CRP), reflective of systemic chronic low-grade inflammation, is a marker associated with cardiovascular disease (CVD). One of the mechanisms through which physical activity might promote cardiovascular health is by preventing changes in inflammation biomarkers, such as CRP. The present study examined the association of self-reported physical activity with an inflammation biomarker, high-sensitivity CRP (hs-CRP), in a population-based cohort of clinically healthy 58-year-old men. Compared with a sedentary lifestyle both moderate (1.81 [0.94-3.69] vs 1.28 [0.55-2.90] mg/L; P < .05) and vigorous physical activity (1.81 [0.94-3.69] vs 0.88 [0.42-1.81] mg/L; P < .001) were associated with decrease in hs-CRP levels. In summary, we identified an association between self-reported leisure time physical activity and hs-CRP in a cross-sectional study of healthy 58-year-old men, with decreased levels of CRP by increased intensities of physical activity. PMID- 22072643 TI - Serum bilirubin level is negatively correlated with disease progression of peripheral arterial disease: an observational cohort study. AB - We determined whether low bilirubin level is a risk factor for peripheral arterial disease (PAD). We recruited 318 patients with PAD and 100 healthy volunteers. Patients were divided into 4 groups by the Fontaine classification for PAD, namely, group 1 (grade 1, n = 4); group 2 (grade 2, n = 114), group 3 (grade 3, n = 164), and group 4 (grade 4, n = 36). Total bilirubin (T-BIL), direct bilirubin (D-BIL), and indirect bilirubin (I-BIL) levels were compared using stepwise multiple regressions adjusted for selected factors. After adjusting for gender, age, smoking, and diastolic blood pressure, serum levels of T-BIL, D-BIL, and I-BIL were significantly lower in the PAD group (P < .05). Patients with grade 4 PAD showed significantly (P < .05) lower levels of T-BIL when compared with grade 2 patients. We concluded that serum bilirubin levels are negatively correlated with the severity and progression of PAD. PMID- 22072644 TI - Complete genome sequence of the animal pathogen Listeria ivanovii, which provides insights into host specificities and evolution of the genus Listeria. AB - We report the complete and annotated genome sequence of the animal pathogen Listeria ivanovii subsp. ivanovii strain PAM 55 (serotype 5), isolated in 1997 in Spain from an outbreak of abortion in sheep. The sequence and its analysis are available at an interactive genome browser at the Institut Pasteur (http://genolist.pasteur.fr/LivaList/). PMID- 22072645 TI - Genome sequence of Pseudomonas putida strain B6-2, a superdegrader of polycyclic aromatic hydrocarbons and dioxin-like compounds. AB - Pseudomonas putida strain B6-2 can efficiently degrade environmental pollutants/toxicants, such as polycyclic aromatic hydrocarbons and dioxin-like compounds, and has unique tolerance to organic solvents. Here, we present a 6.24 Mb draft genome sequence of B6-2, which could provide further insights into the biodegradative mechanisms of a diverse range of chemical compounds. PMID- 22072646 TI - Draft genome sequence of Dietzia alimentaria 72T, belonging to the family Dietziaceae, isolated from a traditional Korean food. AB - Actinobacterial strain 72(T), named Dietzia alimentaria, which belongs to the family Dietziaceae, was isolated from a traditional Korean food made from clams. The draft genome sequence of D. alimentaria 72(T) contains 3,352,817 bp, with a G+C content of 67.34%. PMID- 22072647 TI - Genome sequence of clinical isolate Mycobacterium tuberculosis NCGM2209. AB - We report the annotated genome sequence of a clinical isolate, Mycobacterium tuberculosis strain NCGM2209, which belongs to the "Beijing family" and was isolated in Japan. PMID- 22072648 TI - Genome sequence of Desulfovibrio sp. A2, a highly copper resistant, sulfate reducing bacterium isolated from effluents of a zinc smelter at the Urals. AB - Desulfovibrio sp. A2 is an anaerobic gram-negative sulfate-reducing bacterium with remarkable tolerance to copper. It was isolated from wastewater effluents of a zinc smelter at the Urals. Here, we report the 4.2-Mb draft genome sequence of Desulfovibrio sp. A2 and identify potential copper resistance mechanisms. PMID- 22072649 TI - Draft genome sequence of the biocontrol bacterium Pseudomonas putida B001, an oligotrophic bacterium that induces systemic resistance to plant diseases. AB - Pseudomonas putida B001 is a rhizobacterium that was isolated on the basis of its abilities to grow under low-nutrient conditions and induce systemic resistance against bacterial, fungal, and viral diseases of plants. Here we report the draft genome sequence and automatic annotation of strain B001. Comparison of this sequence to the sequenced genome of P. putida KT2440 points to a subset of gene functions that may be related to the defense-inducing functions of B001. PMID- 22072650 TI - Draft genome sequence of Bizionia argentinensis, isolated from Antarctic surface water. AB - A psychrotolerant marine bacterial strain, designated JUB59(T), was isolated from Antarctic surface seawater and classified as a new species of the genus Bizionia. Here, we present the first draft genome sequence for this genus, which suggests interesting features such as UV resistance, hydrolytic exoenzymes, and nitrogen metabolism. PMID- 22072651 TI - Genome sequence of Bifidobacterium breve DPC 6330, a strain isolated from the human intestine. AB - The draft genome of Bifidobacterium breve DPC 6330, isolated from an elderly patient, was determined. B. breve DPC 6330 was previously identified to synthesize the beneficial metabolite conjugated linoleic acid from free linoleic acid. The sequence will allow identification and characterization of the genetic determinants of its putative beneficial properties. PMID- 22072652 TI - Draft genome sequence of Bacteroides faecis MAJ27T, a strain isolated from human feces. AB - Despite the ecological importance of the dominant gut bacteria Bacteroides, few genomes have been defined. The Gram-negative, strictly anaerobic intestinal bacterium Bacteroides faecis MAJ27(T) was isolated from the feces of a healthy adult. Here, the draft genome sequence of the type strain B. faecis MAJ27 (6.11 Mbp) is reported. PMID- 22072653 TI - Draft genome sequence of the biocontrol bacterium Chromobacterium sp. strain C 61. AB - Chromobacterium sp. strain C-61 is a plant-associated bacterium with proven capacities to suppress plant diseases. Here, we report the draft genome sequence and automatic annotation of strain C-61. A comparison of this sequence to the sequenced genome of Chromobacterium violaceum ATCC 12472 indicates the novelty of C-61 and a subset of gene functions that may be related to its biocontrol activities. PMID- 22072654 TI - From synapse to nucleus and back again--communication over distance within neurons. AB - How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions. PMID- 22072655 TI - Short- and long-term plasticity at the axon initial segment. AB - The axon initial segment (AIS) is a highly specialized neuronal subregion that is the site of action potential initiation and the boundary between axonal and somatodendritic compartments. In recent years, our understanding of the molecular structure of the AIS, its maturation, and its multiple fundamental roles in neuronal function has seen major advances. We are beginning to appreciate that the AIS is dynamically regulated, both over short timescales via adaptations in ion channel function, and long timescales via activity-dependent structural reorganization. Here, we review results from this emerging field highlighting how structural and functional plasticity relate to the development of the initial segment, and to neuronal disorders linked to AIS dysfunction. PMID- 22072657 TI - The role of microglia in the healthy brain. AB - Microglia were recently shown to play unexpected roles in normal brain development and adult physiology. This has begun to dramatically change our view of these resident "immune" cells. Here, we briefly review topics covered in our 2011 Society for Neuroscience minisymposium "The Role of Microglia in the Healthy Brain." This summary is not meant to be a comprehensive review of microglia physiology, but rather to share new results and stimulate further research into the cellular and molecular mechanisms by which microglia influence postnatal development, adult neuronal plasticity, and circuit function. PMID- 22072656 TI - Rapid estrogen signaling in the brain: implications for the fine-tuning of neuronal circuitry. AB - Rapid actions of estrogens were first described >40 years ago. However, the importance of rapid estrogen-mediated actions in the CNS is only now becoming apparent. Several lines of evidence demonstrate that rapid estrogen-mediated signaling elicits potent effects on molecular and cellular events, resulting in the "fine-tuning" of neuronal circuitry. At an ultrastructural level, the details of estrogen receptor localization and how these are regulated by the circulating hormone and age are now becoming evident. Furthermore, the mechanisms that allow membrane-associated estrogen receptors to couple with intracellular signaling pathways are also now being revealed. Elucidation of complex actions of rapid estrogen-mediated signaling on synaptic proteins, connectivity, and synaptic function in pyramidal neurons has demonstrated that this neurosteroid engages specific mechanisms in different areas of the brain. The regulation of synaptic properties most likely underlies the fine-tuning of neuronal circuitry. This in turn may influence how learned behaviors are encoded by different circuitry in male and female subjects. Importantly, as estrogens have been suggested as potential treatments of a number of disorders of the CNS, advancements in our understanding of rapid estrogen signaling in the brain will serve to aid in the development of potential novel estrogen-based treatments. PMID- 22072658 TI - Cellular reprogramming: recent advances in modeling neurological diseases. AB - The remarkable advances in cellular reprogramming have made it possible to generate a renewable source of human neurons from fibroblasts obtained from skin samples of neonates and adults. As a result, we can now investigate the etiology of neurological diseases at the cellular level using neuronal populations derived from patients, which harbor the same genetic mutations thought to be relevant to the risk for pathology. Therapeutic implications include the ability to establish new humanized disease models for understanding mechanisms, conduct high throughput screening for novel biogenic compounds to reverse or prevent the disease phenotype, identify and engineer genetic rescue of causal mutations, and develop patient-specific cellular replacement strategies. Although this field offers enormous potential for understanding and treating neurological disease, there are still many issues that must be addressed before we can fully exploit this technology. Here we summarize several recent studies presented at a symposium at the 2011 annual meeting of the Society for Neuroscience, which highlight innovative approaches to cellular reprogramming and how this revolutionary technique is being refined to model neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorders, schizophrenia, familial dysautonomia, and Alzheimer's disease. PMID- 22072659 TI - The neurophysiology and pathology of brain zinc. AB - Our understanding of the roles played by zinc in the physiological and pathological functioning of the brain is rapidly expanding. The increased availability of genetically modified animal models, selective zinc-sensitive fluorescent probes, and novel chelators is producing a remarkable body of exciting new data that clearly establishes this metal ion as a key modulator of intracellular and intercellular neuronal signaling. In this Mini-Symposium, we will review and discuss the most recent findings that link zinc to synaptic function as well as the injurious effects of zinc dyshomeostasis within the context of neuronal death associated with major human neurological disorders, including stroke, epilepsy, and Alzheimer's disease. PMID- 22072660 TI - Local RNA translation at the synapse and in disease. AB - Local regulation of protein synthesis in neurons has emerged as a leading research focus because of its importance in synaptic plasticity and neurological diseases. The complexity of neuronal subcellular domains and their distance from the soma demand local spatial and temporal control of protein synthesis. Synthesis of many synaptic proteins, such as GluR and PSD-95, is under local control. mRNA binding proteins (RBPs), such as FMRP, function as key regulators of local RNA translation, and the mTORC1 pathway acts as a primary signaling cascade for regulation of these proteins. Much of the regulation occurs through structures termed RNA granules, which are based on reversible aggregation of the RBPs, some of which have aggregation prone domains with sequence features similar to yeast prion proteins. Mutations in many of these RBPs are associated with neurological diseases, including FMRP in fragile X syndrome; TDP-43, FUS (fused in sarcoma), angiogenin, and ataxin-2 in amyotrophic lateral sclerosis; ataxin-2 in spinocerebellar ataxia; and SMN (survival of motor neuron protein) in spinal muscular atrophy. PMID- 22072661 TI - Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function. AB - Melanopsin imparts an intrinsic photosensitivity to a subclass of retinal ganglion cells (ipRGCs). Generally thought of as irradiance detectors, ipRGCs target numerous brain regions involved in non-image-forming vision. ipRGCs integrate their intrinsic, melanopsin-mediated light information with rod/cone signals relayed via synaptic connections to influence light-dependent behaviors. Early observations indicated diversity among these cells and recently several specific subtypes have been identified. These subtypes differ in morphological and physiological form, controlling separate functions that range from biological rhythm via circadian photoentrainment, to protective behavioral responses including pupil constriction and light avoidance, and even image-forming vision. In this Mini-Symposium review, we will discuss some recent findings that highlight the diversity in both form and function of these recently discovered atypical photoreceptors. PMID- 22072662 TI - Thalamic contributions to Basal Ganglia-related behavioral switching and reinforcement. AB - Although the existence of prominent connections between the intralaminar thalamic nuclei and the basal ganglia has long been established, the limited knowledge of the functional relevance of this network has considerably hampered progress in our understanding of the neural mechanisms by which the thalamostriatal system integrates and regulates the basal ganglia circuitry. In this brief commentary, we will address this gap of knowledge through a discussion of the key points of a symposium entitled "Thalamic Contributions to Basal Ganglia-Related Behavioral Switching and Reinforcement" that will be presented at the 2011 Society for Neuroscience meeting. Recent anatomical and physiological data that support the role of the thalamostriatal system in action selection, attentional shifting, and reinforcement will be discussed. We will also address the possibility that degeneration of the thalamostriatal system could underlie some of the deficits in redirection of attention in response to salient stimuli seen in Parkinson's disease. PMID- 22072663 TI - Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones. AB - While much is known about the mechanisms that underlie sleep and circadian rhythms, the investigation into sex differences and gonadal steroid modulation of sleep and biological rhythms is in its infancy. There is a growing recognition of sex disparities in sleep and rhythm disorders. Understanding how neuroendocrine mediators and sex differences influence sleep and biological rhythms is central to advancing our understanding of sleep-related disorders. While it is known that ovarian steroids affect circadian rhythms in rodents, the role of androgen is less understood. Surprising findings that androgens, acting via androgen receptors in the master "circadian clock" within the suprachiasmatic nucleus, modulate photic effects on activity in males point to novel mechanisms of circadian control. Work in aromatase-deficient mice suggests that some sex differences in photic responsiveness are independent of gonadal hormone effects during development. In parallel, aspects of sex differences in sleep are also reported to be independent of gonadal steroids and may involve sex chromosome complement. This a summary of recent work illustrating how sex differences and gonadal hormones influence sleep and circadian rhythms that was presented at a Mini-Symposium at the 2011 annual meeting of the Society for Neuroscience. PMID- 22072664 TI - The placebo effect: advances from different methodological approaches. AB - There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain, and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological, and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge. PMID- 22072666 TI - Toward a neurobiological model of cue-induced self-control in decision making: relevance to addiction and obesity. PMID- 22072665 TI - Large-scale automated histology in the pursuit of connectomes. AB - How does the brain compute? Answering this question necessitates neuronal connectomes, annotated graphs of all synaptic connections within defined brain areas. Further, understanding the energetics of the brain's computations requires vascular graphs. The assembly of a connectome requires sensitive hardware tools to measure neuronal and neurovascular features in all three dimensions, as well as software and machine learning for data analysis and visualization. We present the state of the art on the reconstruction of circuits and vasculature that link brain anatomy and function. Analysis at the scale of tens of nanometers yields connections between identified neurons, while analysis at the micrometer scale yields probabilistic rules of connection between neurons and exact vascular connectivity. PMID- 22072667 TI - Dendritic spine dynamics regulate the long-term stability of synaptic plasticity. AB - Long-term synaptic plasticity requires postsynaptic influx of Ca2+ and is accompanied by changes in dendritic spine size. Unless Ca2+ influx mechanisms and spine volume scale proportionally, changes in spine size will modify spine Ca2+ concentrations during subsequent synaptic activation. We show that the relationship between Ca2+ influx and spine volume is a fundamental determinant of synaptic stability. If Ca2+ influx is undercompensated for increases in spine size, then strong synapses are stabilized and synaptic strength distributions have a single peak. In contrast, overcompensation of Ca2+ influx leads to binary, persistent synaptic strengths with double-peaked distributions. Biophysical simulations predict that CA1 pyramidal neuron spines are undercompensating. This unifies experimental findings that weak synapses are more plastic than strong synapses, that synaptic strengths are unimodally distributed, and that potentiation saturates for a given stimulus strength. We conclude that structural plasticity provides a simple, local, and general mechanism that allows dendritic spines to foster both rapid memory formation and persistent memory storage. PMID- 22072669 TI - Integrins modulate relapse to cocaine-seeking. AB - Relapse to cocaine-seeking involves impairments in plasticity at glutamatergic synapses in the nucleus accumbens. Integrins are cell adhesion molecules that bind to the extracellular matrix and regulate aspects of synaptic plasticity, including glutamate receptor trafficking. To determine a role for integrins in cocaine-seeking, rats were trained to self-administer cocaine, the operant response extinguished, and cocaine-seeking induced by a conditioned cue or noncontingent cocaine injection. This cocaine self-administration protocol reduced the content of the beta3 integrin subunit in postsynaptic density of the accumbens core at 24 h after the last self-administration session. However, after 3 weeks of forced abstinence plus extinction training, the level of beta3 was elevated and was further regulated over 120 min during cocaine-induced drug seeking. A small peptide ligand [arginine-glycine-aspartate (RGD)] that mimics extracellular matrix protein binding to integrins was microinjected into the accumbens core during self-administration or extinction training, or just before cocaine-reinstated drug seeking. The daily RGD injections during self administration or just before a reinstatement session inhibited cocaine-induced drug-seeking, while RGD microinjection during extinction training was without consequence on reinstated cocaine-seeking. Daily RGD during self-administration also prevented the enduring changes in beta3 levels. Finally, reduced surface expression of the GluR2 subunit of the AMPA receptor is associated with cocaine seeking, and daily RGD microinjections during self-administration training normalized the surface expression of GluR2. Together, these data indicate that the regulation integrins may contribute to cocaine-reinstated drug-seeking, in part by promoting reduced GluR2 surface expression. PMID- 22072668 TI - Cosine directional tuning of theta cell burst frequencies: evidence for spatial coding by oscillatory interference. AB - The rodent septohippocampal system contains "theta cells," which burst rhythmically at 4-12 Hz, but the functional significance of this rhythm remains poorly understood (Buzsaki, 2006). Theta rhythm commonly modulates the spike trains of spatially tuned neurons such as place (O'Keefe and Dostrovsky, 1971), head direction (Tsanov et al., 2011a), grid (Hafting et al., 2005), and border cells (Savelli et al., 2008; Solstad et al., 2008). An "oscillatory interference" theory has hypothesized that some of these spatially tuned neurons may derive their positional firing from phase interference among theta oscillations with frequencies that are modulated by the speed and direction of translational movements (Burgess et al., 2005, 2007). This theory is supported by studies reporting modulation of theta frequency by movement speed (Rivas et al., 1996; Geisler et al., 2007; Jeewajee et al., 2008a), but modulation of theta frequency by movement direction has never been observed. Here we recorded theta cells from hippocampus, medial septum, and anterior thalamus of freely behaving rats. Theta cell burst frequencies varied as the cosine of the rat's movement direction, and this directional tuning was influenced by landmark cues, in agreement with predictions of the oscillatory interference theory. Computer simulations and mathematical analysis demonstrated how a postsynaptic neuron can detect location dependent synchrony among inputs from such theta cells, and thereby mimic the spatial tuning properties of place, grid, or border cells. These results suggest that theta cells may serve a high-level computational function by encoding a basis set of oscillatory signals that interfere with one another to synthesize spatial memory representations. PMID- 22072670 TI - Optimal control of natural eye-head movements minimizes the impact of noise. AB - When shifting gaze to foveate a new target, humans mostly choose a unique set of eye and head movements from an infinite number of possible combinations. This stereotypy suggests that a general principle governs the movement choice. Here, we show that minimizing the impact of uncertainty, i.e., noise affecting motor performance, can account for the choice of combined eye-head movements. This optimization criterion predicts all major features of natural eye-head movements including the part where gaze is already on target and the eye counter-rotates such as movement durations, relative eye-head contributions, velocity profiles, and the dependency of gaze shifts on initial eye position. As a critical test of this principle, we show that it also correctly predicts changes in eye and head movement imposed by an experimental increase in the head moment of inertia. This suggests that minimizing the impact of noise is a simple and powerful principle that explains the choice of a unique set of movement profiles and segment coordination in goal-directed action. PMID- 22072671 TI - Deletion of densin-180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction. AB - Densin is an abundant scaffold protein in the postsynaptic density (PSD) that forms a high-affinity complex with alphaCaMKII and alpha-actinin. To assess the function of densin, we created a mouse line with a null mutation in the gene encoding it (LRRC7). Homozygous knock-out mice display a wide variety of abnormal behaviors that are often considered endophenotypes of schizophrenia and autism spectrum disorders. At the cellular level, loss of densin results in reduced levels of alpha-actinin in the brain and selective reduction in the localization of mGluR5 and DISC1 in the PSD fraction, whereas the amounts of ionotropic glutamate receptors and other prominent PSD proteins are unchanged. In addition, deletion of densin results in impairment of mGluR- and NMDA receptor-dependent forms of long-term depression, alters the early dynamics of regulation of CaMKII by NMDA-type glutamate receptors, and produces a change in spine morphology. These results indicate that densin influences the function of mGluRs and CaMKII at synapses and contributes to localization of mGluR5 and DISC1 in the PSD fraction. They are consistent with the hypothesis that mutations that disrupt the organization and/or dynamics of postsynaptic signaling complexes in excitatory synapses can cause behavioral endophenotypes of mental illness. PMID- 22072672 TI - Adaptation to conflict via context-driven anticipatory signals in the dorsomedial prefrontal cortex. AB - Behavioral interference elicited by competing response tendencies adapts to contextual changes. Recent nonhuman primate research suggests a key mnemonic role of distinct prefrontal cells in supporting such context-driven behavioral adjustments by maintaining conflict information across trials, but corresponding prefrontal functions have yet to be probed in humans. Using event-related functional magnetic resonance imaging, we investigated the human neural substrates of contextual adaptations to conflict. We found that a neural system comprising the rostral dorsomedial prefrontal cortex and portions of the dorsolateral prefrontal cortex specifically encodes the history of previously experienced conflict and influences subsequent adaptation to conflict on a trial by-trial basis. This neural system became active in anticipation of stimulus onsets during preparatory periods and interacted with a second neural system engaged during the processing of conflict. Our findings suggest that a dynamic interaction between a system that represents conflict history and a system that resolves conflict underlies the contextual adaptation to conflict. PMID- 22072673 TI - On the distribution of firing rates in networks of cortical neurons. AB - The distribution of in vivo average firing rates within local cortical networks has been reported to be highly skewed and long tailed. The distribution of average single-cell inputs, conversely, is expected to be Gaussian by the central limit theorem. This raises the issue of how a skewed distribution of firing rates might result from a symmetric distribution of inputs. We argue that skewed rate distributions are a signature of the nonlinearity of the in vivo f-I curve. During in vivo conditions, ongoing synaptic activity produces significant fluctuations in the membrane potential of neurons, resulting in an expansive nonlinearity of the f-I curve for low and moderate inputs. Here, we investigate the effects of single-cell and network parameters on the shape of the f-I curve and, by extension, on the distribution of firing rates in randomly connected networks. PMID- 22072674 TI - Morphine protects against intracellular amyloid toxicity by inducing estradiol release and upregulation of Hsp70. AB - Certain experimental models support morphine can play a beneficial role against damage in the neuronal system. In this study, we find morphine as well as endomorphin-1 and endomorphin-2 can protect against intracellular amyloid beta (iAbeta) toxicity in human and rat primary neuronal cultures and in rat brains in vivo. Morphine reverses the electrophysiological changes induced by iAbeta, including current density, resting membrane potential and capacitance. Also morphine improves the spatial memory performance in rats infected by iAbeta packaged virus and in APP/PS1 mice in Morris water maze tests. Morphine protection is mediated through inducing estradiol release in hippocampal neurons measured by ELISA and liquid chromatography-mass spectrometry, possibly by increasing P450 cytochrome aromatase activity. Released estradiol induces upregulation of heat shock protein 70 (Hsp70). Hsp70 protects against intracellular amyloid toxicity by rescuing proteasomal activity which is impaired by iAbeta. This is the first time, to our knowledge, that induction of estradiol release in hippocampal neurons by morphine is reported. Our data may contribute to both Alzheimer's disease therapy and pain clinics where morphine is widely used. PMID- 22072675 TI - CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. AB - The protective/neurotoxic role of fractalkine (CX3CL1) and its receptor CX3C chemokine receptor 1 (CX3CR1) signaling in neurodegenerative disease is an intricate and highly debated research topic and it is becoming even more complicated as new studies reveal discordant results. It appears that the CX3CL1/CX3CR1 axis plays a direct role in neurodegeneration and/or neuroprotection depending on the CNS insult. However, all the above studies focused on the role of CX3CL1/CX3CR1 signaling in pathological conditions, ignoring the relevance of CX3CL1/CX3CR1 signaling under physiological conditions. No approach to date has been taken to decipher the significance of defects in CX3CL1/CX3CR1 signaling in physiological condition. In the present study we used CX3CR1-/-, CX3CR1+/-, and wild-type mice to investigate the physiological role of CX3CR1 receptor in cognition and synaptic plasticity. Our results demonstrate for the first time that mice lacking the CX3CR1 receptor show contextual fear conditioning and Morris water maze deficits. CX3CR1 deficiency also affects motor learning. Importantly, mice lacking the receptor have a significant impairment in long-term potentiation (LTP). Infusion with IL-1beta receptor antagonist significantly reversed the deficit in cognitive function and impairment in LTP. Our results reveal that under physiological conditions, disruption in CX3CL1 signaling will lead to impairment in cognitive function and synaptic plasticity via increased action of IL-1beta. PMID- 22072676 TI - Segregation and pathfinding of callosal axons through EphA3 signaling. AB - The corpus callosum, composed of callosal axons, is the largest structure among commissural connections in eutherian animals. Axon pathfinding of callosal neurons has been shown to be guided by intermediate targets, such as midline glial structures. However, it has not yet been understood completely how axon axon interactions, another major mechanism for axon pathfinding, are involved in the pathfinding of callosal neurons. Here, we show that callosal axons from the medial and lateral regions of the mouse cerebral cortex pass through the dorsal and ventral parts, respectively, of the corpus callosum. Using an explant culture system, we observed that the axons from the medial and lateral cortices were segregated from each other in vitro, and that this segregation was attenuated by inhibition of EphA3 signaling. We also found that knockdown of EphA3, which is preferentially expressed in the lateral cortex, resulted in disorganized segregation of the callosal axons and disrupted axon pathfinding in vivo. These results together suggest the role of axonal segregation in the corpus callosum, mediated at least in part by EphA3, in correct pathfinding of callosal neurons. PMID- 22072677 TI - The Liprin homology domain is essential for the homomeric interaction of SYD 2/Liprin-alpha protein in presynaptic assembly. AB - Synapses are asymmetric structures that are specialized for neuronal signal transduction. A unique set of proteins is present at the presynaptic active zone, which is a core structure essential for neurotransmitter release. In Caenorhabditis elegans HSN neurons, SYD-2, a Liprin-alpha family protein, acts together with a GAP protein SYD-1 to promote presynaptic assembly. Previous studies have shown that elevating the activity of syd-2 can bypass the requirement of syd-1. Liprin-alpha proteins are composed of coiled-coil-rich regions in the N-terminal half, which mediate interactions with adapter proteins at the presynaptic active zone, and three SAM domains in the C terminus, which bind proteins such as LAR receptor tyrosine phosphatase. To address the molecular mechanism by which SYD-2 activity is regulated, we performed structure-function studies. By monitoring the ability of SYD-2 transgenes to rescue syd-2(lf) and to suppress syd-1(lf) phenotypes in HSN neuron synapses, we identified the N terminal half of SYD-2 as minimally required for rescuing syd-2(lf) phenotypes. A highly conserved short coiled-coil segment named Liprin Homology 1 (LH1) domain is both necessary and sufficient to suppress syd-1(lf) defects. We show that the LH1 domain forms a dimer and promotes further oligomerization and/or complex formation of SYD-2/Liprin-alpha proteins. The role of the LH1 domain in presynaptic assembly can be partially complemented by artificial dimerization. These findings suggest a model by which the self-assembly of SYD-2/Liprin-alpha proteins mediated by the coiled-coil LH1 domain is one of the key steps to the accumulation of presynaptic components at nascent synaptic junctions. PMID- 22072678 TI - Spinocerebellar ataxia type 7 cerebellar disease requires the coordinated action of mutant ataxin-7 in neurons and glia, and displays non-cell-autonomous bergmann glia degeneration. AB - Spinocerebellar ataxia type 7 (SCA7) is a dominantly inherited disorder characterized by cerebellum and brainstem neurodegeneration. SCA7 is caused by a CAG/polyglutamine (polyQ) repeat expansion in the ataxin-7 gene. We previously reported that directed expression of polyQ-ataxin-7 in Bergmann glia (BG) in transgenic mice leads to ataxia and non-cell-autonomous Purkinje cell (PC) degeneration. To further define the cellular basis of SCA7, we derived a conditional inactivation mouse model by inserting a loxP-flanked ataxin-7 cDNA with 92 repeats into the translational start site of the murine prion protein (PrP) gene in a bacterial artificial chromosome (BAC). The PrP-floxed-SCA7-92Q BAC mice developed neurological disease, and exhibited cerebellar degeneration and BG process loss. To inactivate polyQ-ataxin-7 expression in specific cerebellar cell types, we crossed PrP-floxed-SCA7-92Q BAC mice with Gfa2-Cre transgenic mice (to direct Cre to BG) or Pcp2-Cre transgenic mice (which yields Cre in PCs and inferior olive). Excision of ataxin-7 from BG partially rescued the behavioral phenotype, but did not prevent BG process loss or molecular layer thinning, while excision of ataxin-7 from PCs and inferior olive provided significantly greater rescue and prevented both pathological changes, revealing a non-cell-autonomous basis for BG pathology. When we prevented expression of mutant ataxin-7 in BG, PCs, and inferior olive by deriving Gfa2-Cre;Pcp2-Cre;PrP floxed-SCA7-92Q BAC triple transgenic mice, we noted a dramatic improvement in SCA7 disease phenotypes. These findings indicate that SCA7 disease pathogenesis involves a convergence of alterations in a variety of different cell types to fully recapitulate the cerebellar degeneration. PMID- 22072679 TI - Hippocampal GluA1-containing AMPA receptors mediate context-dependent sensitization to morphine. AB - Glutamatergic systems, including AMPA receptors (AMPARs), are involved in opiate induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic AMPAR expression in the hippocampus, a brain area that is critically involved in learning and memory. These changes could be observed 1 week after the treatment, but only when mice developed context-dependent behavioral sensitization to morphine in which morphine treatment was associated with drug administration environment. Context dependent behavioral sensitization to morphine was also associated with increased basal synaptic transmission and disrupted hippocampal long-term potentiation (LTP), whereas these effects were less robust when morphine administration was not paired with the drug administration environment. Interestingly, some effects may be related to the prior history of morphine exposure in the drug-associated environment, since alterations of AMPAR expression, basal synaptic transmission, and LTP were observed in mice that received a saline challenge 1 week after discontinuation of morphine treatment. Furthermore, we demonstrated that phosphorylation of GluA1 AMPAR subunit plays a critical role in the acquisition and expression of context-dependent behavioral sensitization, as this behavior is blocked by a viral vector that disrupts GluA1 phosphorylation. These data provide evidence that glutamatergic signaling in the hippocampus plays an important role in context-dependent sensitization to morphine and supports further investigation of glutamate-based strategies for treating opiate addiction. PMID- 22072680 TI - Abeta inhibition of ionic conductance in mouse basal forebrain neurons is dependent upon the cellular prion protein PrPC. AB - Current therapies for Alzheimer's disease (AD) address a loss of cholinergic neurons, while accumulation of neurotoxic amyloid beta (Abeta) peptide assemblies is thought central to molecular pathogenesis. Overlaps may exist between prionopathies and AD wherein Abeta oligomers bind to the cellular prion protein PrP(C) and inhibit synaptic plasticity in the hippocampus (Lauren et al., 2009). Here we applied oligomeric Abeta to neurons with different PrP (Prnp) gene dosage. Whole-cell recordings were obtained from dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. In wild-type (wt) mice, Abeta1-42 evoked a concentration-dependent reduction of whole-cell outward currents in a voltage range between -30 and +30 mV; reduction occurred through a combined modulation of a suite of potassium conductances including the delayed rectifier (I(K)), the transient outward (I(A)), and the iberiotoxin sensitive (calcium-activated potassium, I(C)) currents. Inhibition was not seen with Abeta42-1 peptide, while Abeta1-42-induced responses were reduced by application of anti-PrP antibody, attenuated in cells from Prnp0/+ hemizygotes, and absent in Prnp0/0 homozygotes. Similarly, amyloidogenic amylin peptide depressed DBB whole-cell currents in DBB cells from wt mice, but not Prnp0/0 homozygotes. While prior studies give broad support for a neuroprotective function for PrP(C), our data define a latent pro-pathogenic role in the presence of amyloid assemblies. PMID- 22072681 TI - Inhibition of the Ca2+-dependent K+ channel, KCNN4/KCa3.1, improves tissue protection and locomotor recovery after spinal cord injury. AB - Spinal cord injury (SCI) triggers inflammatory responses that involve neutrophils, macrophages/microglia and astrocytes and molecules that potentially cause secondary tissue damage and functional impairment. Here, we assessed the contribution of the calcium-dependent K+ channel KCNN4 (KCa3.1, IK1, SK4) to secondary damage after moderate contusion lesions in the lower thoracic spinal cord of adult mice. Changes in KCNN4 mRNA levels (RT-PCR), KCa3.1 protein expression (Western blots), and cellular expression (immunofluorescence) in the mouse spinal cord were monitored between 1 and 28 d after SCI. KCNN4 mRNA and KCa3.1 protein rapidly increased after SCI; double labeling identified astrocytes as the main cellular source accounting for this upregulation. Locomotor function after SCI, evaluated for 28 d in an open-field test using the Basso Mouse Scale, was improved in a dose-dependent manner by treating mice with a selective inhibitor of KCa3.1 channels, TRAM-34 (triarylmethane-34). Improved locomotor function was accompanied by reduced tissue loss at 28 d and increased neuron and axon sparing. The rescue of tissue by TRAM-34 treatment was preceded by reduced expression of the proinflammatory mediators, tumor necrosis factor-alpha and interleukin-1beta in spinal cord tissue at 12 h after injury, and reduced expression of inducible nitric oxide synthase at 7 d after SCI. In astrocytes in vitro, TRAM-34 inhibited Ca2+ signaling in response to metabotropic purinergic receptor stimulation. These results suggest that blocking the KCa3.1 channel could be a potential therapeutic approach for treating secondary damage after spinal cord injury. PMID- 22072682 TI - Real-time functional magnetic resonance imaging neurofeedback for treatment of Parkinson's disease. AB - Self-regulation of brain activity in humans based on real-time feedback of functional magnetic resonance imaging (fMRI) signal is emerging as a potentially powerful, new technique. Here, we assessed whether patients with Parkinson's disease (PD) are able to alter local brain activity to improve motor function. Five patients learned to increase activity in the supplementary motor complex over two fMRI sessions using motor imagery. They attained as much activation in this target brain region as during a localizer procedure with overt movements. Concomitantly, they showed an improvement in motor speed (finger tapping) and clinical ratings of motor symptoms (37% improvement of the motor scale of the Unified Parkinson's Disease Rating Scale). Activation during neurofeedback was also observed in other cortical motor areas and the basal ganglia, including the subthalamic nucleus and globus pallidus, which are connected to the supplementary motor area (SMA) and crucial nodes in the pathophysiology of PD. A PD control group of five patients, matched for clinical severity and medication, underwent the same procedure but did not receive feedback about their SMA activity. This group attained no control of SMA activation and showed no motor improvement. These findings demonstrate that self-modulation of cortico-subcortical motor circuits can be achieved by PD patients through neurofeedback and may result in clinical benefits that are not attainable by motor imagery alone. PMID- 22072683 TI - Ca2+ influx slows single synaptic vesicle endocytosis. AB - Ca2+-dependent synaptic vesicle recycling is critical for maintenance of neurotransmission. However, uncoupling the roles of Ca2+ in synaptic vesicle fusion and retrieval has been difficult, as studies probing the role of Ca2+ in endocytosis relied on measurements of bulk synaptic vesicle retrieval. Here, to dissect the role of Ca2+ in these processes, we used a low signal-to-noise pHluorin-tagged vesicular probe to monitor single synaptic vesicle recycling in rat hippocampal neurons. We show that Ca2+ increases synaptic vesicle fusion probability in the classical sense, but surprisingly decreases the rate of synaptic vesicle retrieval. This negative regulation of synaptic vesicle retrieval is blocked by the Ca2+ chelator, EGTA, as well as FK506, a specific inhibitor of Ca2+-calmodulin-dependent phosphatase calcineurin. The slow time course of aggregate synaptic vesicle retrieval detected during repetitive activity could be explained by a progressive decrease in the rate of synaptic vesicle retrieval during the stimulation train. These results indicate that Ca2+ entry during single action potentials slows the pace of subsequent synaptic vesicle recycling. PMID- 22072684 TI - CX3CL1 is neuroprotective in permanent focal cerebral ischemia in rodents. AB - The chemokine CX3CL1 and its receptor CX3CR1 are constitutively expressed in the nervous system. In this study, we used in vivo murine models of permanent middle cerebral artery occlusion (pMCAO) to investigate the protective potential of CX3CL1. We report that exogenous CX3CL1 reduced ischemia-induced cerebral infarct size, neurological deficits, and caspase-3 activation. CX3CL1-induced neuroprotective effects were long lasting, being observed up to 50 d after pMCAO in rats. The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia and, in vitro, requires the activation of adenosine receptor 1 (A1R). We show that, in the presence of the A1R antagonist 1,3-dipropyl-8-cyclopentylxanthine and in A1R-/- mice, the neuroprotective effect of CX3CL1 on pMCAO was abolished, indicating the critical importance of the adenosine system in CX3CL1 protection also in vivo. In apparent contrast with the above reported data but in agreement with previous findings, cx3cl1-/- and cx3cr1(GFP/GFP) mice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage in cx3cl1-/- ischemic mice. We also report that CX3CL1 induced a different phagocytic activity in wild type and cx3cl1-/- microglia in vitro during cotreatment with the medium conditioned by neurons damaged by oxygen-glucose deprivation. Together, these data suggest that acute administration of CX3CL1 reduces ischemic damage via an adenosine-dependent mechanism and that the absence of constitutive CX3CL1-CX3CR1 signaling changes the outcome of microglia-mediated effects during CX3CL1 administration to ischemic brain. PMID- 22072685 TI - Perirhinal cortex removal dissociates two memory systems in matching-to-sample performance in rhesus monkeys. AB - Dissociations of memory systems are typically made using independent cognitive tests. For example, in monkeys habits have been inferred from performance in object discrimination tests, while non-matching-to-sample tests are thought to measure familiarity resulting from single exposures. Such tests cannot measure individual memory processes accurately when more than one memory process contributes to performance. In process dissociation procedures (PDPs), two memory processes cooperate and compete in the performance of a single cognitive task, allowing quantitative estimates of the contributions of each process. We used PDP to measure the contributions of habits and one-trial memory to visual matching-to sample performance. Sets of test images were shown only once in each daily testing session but were repeated day after day. To produce habits, high frequency images were correct more frequently than other images across days. Habits were manifest in the extent to which choices in the test phase of matching to-sample trials were made to the high-frequency images, regardless of which image had been presented as the sample. One-trial memory was measured by the extent to which choices at test were made to the image that had appeared as the sample on that trial, regardless of habit. Perirhinal cortex removal reduced the contribution of one-trial memory to matching performance, but left both habits and the ability to discriminate images intact. PDP can be applied in monkeys in a way that parallels its use in humans, providing a new tool for investigating the neurobiology of memory in nonhuman animals and for comparing memory across species. PMID- 22072686 TI - Brain activity during ankle proprioceptive stimulation predicts balance performance in young and older adults. AB - Proprioceptive information from the foot/ankle provides important information regarding body sway for balance control, especially in situations where visual information is degraded or absent. Given known increases in catastrophic injury due to falls with older age, understanding the neural basis of proprioceptive processing for balance control is particularly important for older adults. In the present study, we linked neural activity in response to stimulation of key foot proprioceptors (i.e., muscle spindles) with balance ability across the lifespan. Twenty young and 20 older human adults underwent proprioceptive mapping; foot tendon vibration was compared with vibration of a nearby bone in an fMRI environment to determine regions of the brain that were active in response to muscle spindle stimulation. Several body sway metrics were also calculated for the same participants on an eyes-closed balance task. Based on regression analyses, multiple clusters of voxels were identified showing a significant relationship between muscle spindle stimulation-induced neural activity and maximum center of pressure excursion in the anterior-posterior direction. In this case, increased activation was associated with greater balance performance in parietal, frontal, and insular cortical areas, as well as structures within the basal ganglia. These correlated regions were age- and foot-stimulation side independent and largely localized to right-sided areas of the brain thought to be involved in monitoring stimulus-driven shifts of attention. These findings support the notion that, beyond fundamental peripheral reflex mechanisms, central processing of proprioceptive signals from the foot is critical for balance control. PMID- 22072687 TI - Two distinct modes of forebrain circuit dynamics underlie temporal patterning in the vocalizations of young songbirds. AB - Accurate timing is a critical aspect of motor control, yet the temporal structure of many mature behaviors emerges during learning from highly variable exploratory actions. How does a developing brain acquire the precise control of timing in behavioral sequences? To investigate the development of timing, we analyzed the songs of young juvenile zebra finches. These highly variable vocalizations, akin to human babbling, gradually develop into temporally stereotyped adult songs. We find that the durations of syllables and silences in juvenile singing are formed by a mixture of two distinct modes of timing: a random mode producing broadly distributed durations early in development, and a stereotyped mode underlying the gradual emergence of stereotyped durations. Using lesions, inactivations, and localized brain cooling, we investigated the roles of neural dynamics within two premotor cortical areas in the production of these temporal modes. We find that LMAN (lateral magnocellular nucleus of the nidopallium) is required specifically for the generation of the random mode of timing and that mild cooling of LMAN causes an increase in the durations produced by this mode. On the contrary, HVC (used as a proper name) is required specifically for producing the stereotyped mode of timing, and its cooling causes a slowing of all stereotyped components. These results show that two neural pathways contribute to the timing of juvenile songs and suggest an interesting organization in the forebrain, whereby different brain areas are specialized for the production of distinct forms of neural dynamics. PMID- 22072688 TI - Quantitative and integrative proteome analysis of peripheral nerve myelin identifies novel myelin proteins and candidate neuropathy loci. AB - Peripheral nerve myelin facilitates rapid impulse conduction and normal motor and sensory functions. Many aspects of myelin biogenesis, glia-axonal interactions, and nerve homeostasis are poorly understood at the molecular level. We therefore hypothesized that only a fraction of all relevant myelin proteins has been identified so far. Combining gel-based and gel-free proteomic approaches, we identified 545 proteins in purified mouse sciatic nerve myelin, including 36 previously known myelin constituents. By mass spectrometric quantification, the predominant P0, periaxin, and myelin basic protein constitute 21, 16, and 8% of the total myelin protein, respectively, suggesting that their relative abundance was previously misestimated due to technical limitations regarding protein separation and visualization. Focusing on tetraspan-transmembrane proteins, we validated novel myelin constituents using immuno-based methods. Bioinformatic comparison with mRNA-abundance profiles allowed the categorization in functional groups coregulated during myelin biogenesis and maturation. By differential myelin proteome analysis, we found that the abundance of septin 9, the protein affected in hereditary neuralgic amyotrophy, is strongly increased in a novel mouse model of demyelinating neuropathy caused by the loss of prion protein. Finally, the systematic comparison of our compendium with the positions of human disease loci allowed us to identify several candidate genes for hereditary demyelinating neuropathies. These results illustrate how the integration of unbiased proteome, transcriptome, and genome data can contribute to a molecular dissection of the biogenesis, cell biology, metabolism, and pathology of myelin. PMID- 22072689 TI - Tonic nanomolar dopamine enables an activity-dependent phase recovery mechanism that persistently alters the maximal conductance of the hyperpolarization activated current in a rhythmically active neuron. AB - The phases at which network neurons fire in rhythmic motor outputs are critically important for the proper generation of motor behaviors. The pyloric network in the crustacean stomatogastric ganglion generates a rhythmic motor output wherein neuronal phase relationships are remarkably invariant across individuals and throughout lifetimes. The mechanisms for maintaining these robust phase relationships over the long-term are not well described. Here we show that tonic nanomolar dopamine (DA) acts at type 1 DA receptors (D1Rs) to enable an activity dependent mechanism that can contribute to phase maintenance in the lateral pyloric (LP) neuron. The LP displays continuous rhythmic bursting. The activity dependent mechanism was triggered by a prolonged decrease in LP burst duration, and it generated a persistent increase in the maximal conductance (G(max)) of the LP hyperpolarization-activated current (I(h)), but only in the presence of steady state DA. Interestingly, micromolar DA produces an LP phase advance accompanied by a decrease in LP burst duration that abolishes normal LP network function. During a 1 h application of micromolar DA, LP phase recovered over tens of minutes because, the activity-dependent mechanism enabled by steady-state DA was triggered by the micromolar DA-induced decrease in LP burst duration. Presumably, this mechanism restored normal LP network function. These data suggest steady state DA may enable homeostatic mechanisms that maintain motor network output during protracted neuromodulation. This DA-enabled, activity-dependent mechanism to preserve phase may be broadly relevant, as diminished dopaminergic tone has recently been shown to reduce I(h) in rhythmically active neurons in the mammalian brain. PMID- 22072690 TI - Measuring the quality of neuronal identification in ensemble recordings. AB - Technological advances in electrode construction and digital signal processing now allow recording simultaneous extracellular action potential discharges from many single neurons, with the potential to revolutionize understanding of the neural codes for sensory, motor, and cognitive variables. Such studies have revealed the importance of ensemble neural codes, encoding information in the dynamic relationships among the action potential spike trains of multiple single neurons. Although the success of this research depends on the accurate classification of extracellular action potentials to individual neurons, there are no widely used quantitative methods for assessing the quality of the classifications. Here we describe information theoretic measures of action potential waveform isolation applicable to any dataset that have an intuitive, universal interpretation, that are not dependent on the methods or choice of parameters for single-unit isolation, and that have been validated using a dataset of simultaneous intracellular and extracellular neuronal recordings from Sprague Dawley rats. PMID- 22072691 TI - Phox2b-expressing neurons of the parafacial region regulate breathing rate, inspiration, and expiration in conscious rats. AB - The retrotrapezoid nucleus contains Phox2b-expressing glutamatergic neurons (RTN Phox2b neurons) that regulate breathing in a CO2-dependent manner. Here we use channelrhodopsin-based optogenetics to explore how these neurons control breathing in conscious and anesthetized adult rats. Respiratory entrainment (pacing) of breathing frequency (fR) was produced over 57% (anesthetized) and 28% (conscious) of the natural frequency range by burst activation of RTN-Phox2b neurons (3-8 * 0.5-20 ms pulses at 20 Hz). In conscious rats, pacing under normocapnic conditions increased tidal volume (V(T)) and each inspiration was preceded by active expiration, denoting abdominal muscle contraction. During long term pacing V(T) returned to prestimulation levels, suggesting that central chemoreceptors such as RTN-Phox2b neurons regulate V(T) partly independently of their effect on fR. Randomly applied light trains reset the respiratory rhythm and shortened the expiratory phase when the stimulus coincided with late inspiration or early-expiration. Importantly, continuous (20 Hz) photostimulation of the RTN-Phox2b neurons and a saturating CO2 concentration produced similar effects on breathing that were much larger than those elicited by phasic RTN stimulation. In sum, consistent with their anatomical projections, RTN-Phox2b neurons regulate lung ventilation by controlling breathing frequency, inspiration, and active expiration. Adult RTN-Phox2b neurons can entrain the respiratory rhythm if their discharge is artificially synchronized, but continuous activation of these neurons is much more effective at increasing lung ventilation. These results suggest that RTN-Phox2b neurons are no longer rhythmogenic in adulthood and that their average discharge rate may be far more important than their discharge pattern in driving lung ventilation. PMID- 22072692 TI - The anticonvulsant response to valproate in kindled rats is correlated with its effect on neuronal firing in the substantia nigra pars reticulata: a new mechanism of pharmacoresistance. AB - Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy treatment. However, mechanisms of resistance are only incompletely understood. We have recently shown that repeated administration of the AED phenytoin allows selecting resistant and responsive rats from the amygdala kindling model of epilepsy, providing a tool to study mechanisms of AED resistance. We now tested whether individual amygdala-kindled rats also differ in their anticonvulsant response to the major AED valproate (VPA) and which mechanism may underlie the different response to VPA. VPA has been proposed to act, at least in part, by reducing spontaneous activity in the substantia nigra pars reticulata (SNr), a main basal ganglia output structure involved in seizure propagation, seizure control, and epilepsy-induced neuroplasticity. Thus, we evaluated whether poor anticonvulsant response to VPA is correlated with low efficacy of VPA on SNr firing rate and pattern in kindled rats. We found (1) that good and poor VPA responders can be selected in kindled rats by repeatedly determining the effect of VPA on the electrographic seizure threshold, and (2) a significant correlation between the anticonvulsant response to VPA in kindled rats and its effect on SNr firing rate and pattern. The less VPA was able to raise seizure threshold, the lower was the VPA-induced reduction of SNr firing rate and the VPA-induced regularity of SNr firing. The data demonstrate for the first time an involvement of the SNr in pharmacoresistant experimental epilepsy and emphasize the relevance of the basal ganglia as target structures for new treatment options. PMID- 22072693 TI - Glutamate spillover promotes the generation of NMDA spikes. AB - NMDA spikes are prominent in the basal dendrites of cortical pyramidal neurons and greatly expand their ability to integrate synaptic inputs. Calcium (Ca) signals during these spikes are important for synaptic plasticity and fundamentally depend on activation of NMDA receptors. However, the factors that shape the activation of these receptors and the initiation of NMDA spikes remain unclear. Here we examine the properties of NMDA spikes in the basal dendrites of layer 5 pyramidal neurons in the mouse prefrontal cortex. Using two-photon imaging, we demonstrate that NMDA spikes evoke large Ca signals in both postsynaptic spines and nearby dendrites. We find that the dendrite Ca signals depend on NMDA and AMPA receptors but not sodium (Na) or Ca channels. Using voltage-clamp recordings, we show that activation of dendrite NMDA receptors is enhanced by concerted synaptic activity. Blocking glutamate reuptake further increases activation of these receptors and promotes the initiation of NMDA spikes. We conclude that glutamate spillover and recruitment of extrasynaptic receptors contribute to the initiation of NMDA spikes. These results have important implications for how synaptic activity generates both electrical and biochemical signals in dendrites and spines. PMID- 22072694 TI - Overexpression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats. AB - Chronic exposure to addictive drugs enhances cAMP response element binding protein (CREB)-regulated gene expression in nucleus accumbens (NAc), and these effects are thought to reduce the positive hedonic effects of passive cocaine administration. Here, we used viral-mediated gene transfer to produce short- and long-term regulation of CREB activity in NAc shell of rats engaging in volitional cocaine self-administration. Increasing CREB expression in NAc shell markedly enhanced cocaine reinforcement of self-administration behavior, as indicated by leftward (long-term) and upward (short-term) shifts in fixed ratio dose-response curves. CREB also increased the effort exerted by rats to obtain cocaine on more demanding progressive ratio schedules, an effect highly correlated with viral induced modulation of BDNF protein in the NAc shell. CREB enhanced cocaine reinforcement when expressed either throughout acquisition of self-administration or when expression was limited to postacquisition tests, indicating a direct effect of CREB independent of reinforcement-related learning. Downregulating endogenous CREB in NAc shell by expressing a short hairpin RNA reduced cocaine reinforcement in similar tests, while overexpression of a dominant-negative CREB(S133A) mutant had no significant effect on cocaine self-administration. Finally, increasing CREB expression after withdrawal from self-administration enhanced cocaine-primed relapse, while reducing CREB levels facilitated extinction of cocaine seeking, but neither altered relapse induced by cocaine cues or footshock stress. Together, these findings indicate that CREB activity in NAc shell increases the motivation for cocaine during active self-administration or after withdrawal from cocaine. Our results also highlight that volitional and passive drug administration can lead to substantially different behavioral outcomes. PMID- 22072695 TI - Plasticity of prefrontal attention circuitry: upregulated muscarinic excitability in response to decreased nicotinic signaling following deletion of alpha5 or beta2 subunits. AB - Attention depends on cholinergic stimulation of nicotinic and muscarinic acetylcholine receptors in the medial prefrontal cortex. Pyramidal neurons in layer VI of this region express cholinergic receptors of both families and play an important role in attention through their feedback projections to the thalamus. Here, we investigate how nicotinic and muscarinic cholinergic receptors affect the excitability of these neurons using whole-cell recordings in acute brain slices of prefrontal cortex. Since attention deficits have been documented in both rodents and humans having genetic abnormalities in nicotinic receptors, we focus in particular on how the cholinergic excitation of layer VI neurons is altered by genetic deletion of either of two key nicotinic receptor subunits, the accessory alpha5 subunit or the ligand-binding beta2 subunit. We find that the cholinergic excitation of layer VI neurons is dominated by nicotinic receptors in wild-type mice and that the reduction or loss of this nicotinic stimulation is accompanied by a surprising degree of plasticity in excitatory muscarinic receptors. These findings suggest that disrupting nicotinic receptors fundamentally alters the mechanisms and timing of excitation in prefrontal attentional circuitry. PMID- 22072696 TI - Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: a transcranial magnetic stimulation study. AB - Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism. PMID- 22072697 TI - Concurrent exposure to methamphetamine and sexual behavior enhances subsequent drug reward and causes compulsive sexual behavior in male rats. AB - Methamphetamine (Meth) users report having heightened sexual pleasure, numerous sexual partners, and engaging in unprotected sex due to loss of inhibitory control. This compulsive sexual behavior contributes to increased prevalence of sexually transmitted infections, but the neural basis for this is unknown. We previously established a paradigm for compulsive sexual behavior in male rats in which visceral illness induced by lithium chloride was paired with sexual behavior (Davis et al., 2010; Frohmader et al., 2010a). The current study examined the effects of repeated Meth administration on sexual performance, compulsive sexual behavior, and sex or Meth reward. First, results demonstrated that seven daily administrations of 2 mg/kg, but not 1 mg/kg, Meth increased latencies to initiate mating. This impairment was evident 30 min after last Meth administration, but dissipated after 1 or 7 d of subsequent drug abstinence. Repeated 1 mg/kg Meth exposure resulted in compulsive sex-seeking behavior 2 weeks following last Meth administration. This effect was dependent on Meth administration being concurrent with sexual experience and was not observed in sexually experienced animals that received Meth alone. Moreover, concurrent Meth and sexual experience enhanced conditioned place preference (CPP) for Meth, and for concurrent Meth and mating compared with Meth or mating alone. In contrast, CPP for mating alone was decreased. Together, these data indicate that the association between drug use and mating may be required for expression of compulsive sexual behavior and is correlated with increased reward seeking for concurrent Meth exposure and mating. PMID- 22072698 TI - Focal manipulations of formant trajectories reveal a role of auditory feedback in the online control of both within-syllable and between-syllable speech timing. AB - Within the human motor repertoire, speech production has a uniquely high level of spatiotemporal complexity. The production of running speech comprises the traversing of spatial positions with precisely coordinated articulator movements to produce 10-15 sounds/s. How does the brain use auditory feedback, namely the self-perception of produced speech sounds, in the online control of spatial and temporal parameters of multisyllabic articulation? This question has important bearings on the organizational principles of sequential actions, yet its answer remains controversial due to the long latency of the auditory feedback pathway and technical challenges involved in manipulating auditory feedback in precisely controlled ways during running speech. In this study, we developed a novel technique for introducing time-varying, focal perturbations in the auditory feedback during multisyllabic, connected speech. Manipulations of spatial and temporal parameters of the formant trajectory were tested separately on two groups of subjects as they uttered "I owe you a yo-yo." Under these perturbations, significant and specific changes were observed in both the spatial and temporal parameters of the produced formant trajectories. Compensations to spatial perturbations were bidirectional and opposed the perturbations. Furthermore, under perturbations that manipulated the timing of auditory feedback trajectory (slow-down or speed-up), significant adjustments in syllable timing were observed in the subjects' productions. These results highlight the systematic roles of auditory feedback in the online control of a highly over learned action as connected speech articulation and provide a first look at the properties of this type of sensorimotor interaction in sequential movements. PMID- 22072699 TI - Validation of a method for accurate and highly reproducible quantification of brain dopamine transporter SPECT studies. AB - In nuclear medicine brain imaging, it is important to delineate regions of interest (ROIs) so that the outcome is both accurate and reproducible. The purpose of this study was to validate a new time-saving algorithm (DATquan) for accurate and reproducible quantification of the striatal dopamine transporter (DAT) with appropriate radioligands and SPECT and without the need for structural brain scanning. METHODS: In a reconstructed DAT SPECT image, DATquan automatically calculated the ratio at steady state of specifically bound radioligand to nondisplaceable radioligand in tissue (BP(ND)) within striatal ROIs that were delineated by use of a semiautomatic template-based alignment approach. DATquan was tested with (123)I-N-(3-iodoprop-2E-enyl)-2-beta carbomethoxy-3beta-(4-methylphenyl) SPECT images from 15 patients. In each image, ROIs were first manually delineated, and then corresponding BP(ND) values were derived by an experienced physician. Afterward, 2 independent novice operators used DATquan to analyze the same 15 images. The resulting DATquan-derived BP(ND) data were compared with the data retrieved by manual delineation to assess the accuracy and reproducibility of DATquan. Also, the operational aspects of DATquan were assessed on the basis of measurements of the mean running time of the algorithm as well as on the basis of quantification of the overlap of the DATquan delineated ROIs obtained by the 2 operators. RESULTS: The mean algorithm running time was 3 min, and the operators' striatal ROIs had a mean overlap of more than 82%. DATquan-derived BP(ND) values obtained by the 2 operators showed high agreement (the mean difference was 0.00 [SD, 0.05] in the striatum, 0.02 [SD, 0.26] in the putamen, and 0.03 [SD, 0.43] in the caudate nucleus). The interoperator variability was 2.2% (SD, 1.3%) in the striatum, 11.7% (SD, 9.9%) in the putamen, and 12.9% (SD, 4.0%) in the caudate nucleus. DATquan-derived BP(ND) values showed high agreement with the values manually derived by the experienced delineator. CONCLUSION: DATquan is a freely available, accurate, and highly reproducible method for quantification of DAT binding in the brain by SPECT. Once implemented in clinics, DATquan will serve as a useful and time saving tool. PMID- 22072700 TI - Experiences with citrate rather than heparin as an anticoagulant for 18F-FDG labeling of leukocytes. AB - In all reported clinical studies with (18)F-FDG-labeled leukocytes, heparin was used as an anticoagulant during labeling. Theoretically, the substitution of heparin with citrate should be advantageous. METHODS: Blood from healthy controls was sampled in duplicate, anticoagulated with citrate or heparin, and labeled with (18)F-FDG, and the labeling yield was measured. Viability was checked with the trypan blue exclusion technique. Moreover, 4 in vivo PET/CT studies were performed after the reinjection of leukocytes labeled after citrate anticoagulation. RESULTS: The labeling yields obtained with citrate and heparin were not significantly different (P = 0.447). Viability was greater than or equal to 99%. The quality of the PET/CT studies was excellent. In the in vivo studies, the mean labeling yield was 78%-better than or equal to that reported with heparin as an anticoagulant. CONCLUSION: Citrate is at least as effective as heparin as an anticoagulant, does not (unlike heparin) increase granulocyte activation, and should be the preferred anticoagulant for (18)F-FDG labeling of leukocytes. PMID- 22072701 TI - Cardiovascular fitness as a risk factor for amyotrophic lateral sclerosis: indirect evidence from record linkage study. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) appears to be a sporadic disorder in 95% of cases. Although few personal characteristics associated with developing ALS are known, identification of those at risk is essential to any vision of early intervention. There is persistent anecdotal observation that those with ALS are premorbidly physically 'fitter', although such observations are susceptible to bias. Hospital admission for coronary heart disease (CHD) might serve as an objective marker of reduced cardiovascular fitness. METHODS: A record linkage study of two large databases of hospital admissions, the Oxford Record Linkage Study (ORLS) and an English national record linkage dataset of Hospital Episode Statistics was undertaken. The ratio of the rate of ALS in people without a record of CHD to that in those with a record of CHD was calculated, factoring out premature death in both cohorts. Similar analysis for Parkinson's disease (PD) and multiple sclerosis (MS) was undertaken. RESULTS: In the English population, the rate ratio for ALS in the non-CHD cohort, compared with the CHD cohort, was 1.14 (95% CI 1.05 to 1.22); for PD it was 0.95 (95% CI 0.93 to 0.98); and for MS 0.95 (95% CI 0.88 to 1.04). The ORLS data yielded similar findings. CONCLUSIONS: Those without a record of CHD were at modestly higher risk of ALS, but not for PD or MS. This lends support to the assertion that ALS arises within a population who may have relatively higher levels of cardiovascular fitness. PMID- 22072702 TI - Impaired vasoreactivity in mildly disabled CADASIL patients. AB - BACKGROUND AND PURPOSE: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a rare genetic disease caused by NOTCH3 gene mutations. A dysfunction in vasoreactivity has been proposed as an early event in the pathogenesis of the disease. The aim of this study was to verify whether endothelium dependent and/or independent function is altered in CADASIL patients with respect to controls. METHODS: Vasoreactivity was studied by a non-invasive pletismographic method in 49 mildly disabled CADASIL patients (30 65 years, 58% male, Rankin scale <=2) and 25 controls. Endothelium dependent vasodilatation was assessed by reactive hyperaemia (flow mediated dilation peripheral arterial tone (FMD-PAT)) and endothelium independent vasoreactivity by glyceryl trinitrate (GTN) administration (GTN-PAT). RESULTS: Patients and controls showed comparable age, gender and cardiovascular risk factor distribution. GTN-PAT values were significantly lower in CADASIL patients (1.54 (1.01 to 2.25)) than in controls (1.89 (1.61 to 2.59); p=0.041). FMD-PAT scores did not differ between patients and controls (1.88 (1.57 to 2.43) vs 2.08 (1.81 to 2.58); p=0.126) but 17 CADASIL patients (35%) had FMD-PAT scores below the fifth percentile of controls. FMD-PAT and GTN-PAT values correlated both in controls (rho=0.648, p<0.001) and CADASIL patients (rho=0.563, p<0.001). By multivariable logistic regression for clinical and laboratory variables, only GTN PAT (OR 0.39, 95% CI 0.15 to 0.97; p=0.044) was independently associated with FMD PAT below the fifth percentile in CADASIL patients. CONCLUSIONS: The impaired vasoreactivity observed in CADASIL patients highlights the fact that both endothelial and smooth muscle functional alterations may already be present in mildly disabled subjects. The improvement in vascular function could be a new target for pharmacological trials in CADASIL patients. PMID- 22072703 TI - Cortical folding influences migraine aura symptoms in CADASIL. AB - OBJECTIVE: Migraine with aura is a hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). In contrast with the majority of CADASIL patients, some affected subjects never experience visual symptoms during their attacks of migraine with aura. The aim of this study was to determine whether specific morphology of the primary visual cortex is associated with the absence of visual symptoms during migraine aura in CADASIL. METHODS: Patients from a large cohort of CADASIL patients, aged <45 years, and with a modified Rankin's scale <=1 were included in the study. Width and depth of the calcarine sulcus in the primary visual cortex as well as cortical thickness in its neighbourhood were compared between patients with visual and those with non-visual migraine auras. RESULTS: 31 patients had visual symptoms (VA group) while nine reported only non-visual symptoms (NVA group) during their migraine auras. Asymmetry index of the calcarine sulcal depth largely differed between the NVA group and the VA group (0.22+/-0.1 vs -0.004+/ 0.2; p=1.7*10(-6)). The width of the right calcarine sulcus was significantly lower in the VA group (p=0.04) and cortical thickness was larger in the NVA group (p=0.03). CONCLUSION: The absence of visual symptoms during migraine auras was associated with a profound asymmetry of the primary visual cortex. Aura symptoms seem to be linked to the morphology of the primary visual cortex in CADASIL. This finding potentially reflects more general relationships between spreading depression and cortex morphology in migraine with aura. PMID- 22072704 TI - 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. AB - Radiolabeled somatostatin analogs represent valuable tools for both in vivo diagnosis and therapy of neuroendocrine tumors (NETs) because of the frequent tumoral overexpression of somatostatin receptors (sst). The 2 compounds most often used in functional imaging with PET are (68)Ga-DOTATATE and (68)Ga-DOTATOC. Both ligands share a quite similar sst binding profile. However, the in vitro affinity of (68)Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately 10-fold higher than that of (68)Ga-DOTATOC. This difference may affect their efficiency in the detection of NET lesions because it is the sst2 that is predominantly overexpressed in NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs ((68)Ga-DOTATATE and (68)Ga DOTATOC) in the same NET patients. METHODS: Forty patients with metastatic NETs underwent (68)Ga-DOTATOC and (68)Ga-DOTATATE PET/CT as part of the work-up before prospective peptide receptor radionuclide therapy. The performance of both imaging methods was analyzed and compared for the detection of individual lesions per patient and for 8 defined body regions. A region was regarded positive if at least 1 lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUVmax) was compared for concordant lesions and renal parenchyma. RESULTS: Seventy-eight regions were found positive with (68)Ga-DOTATATE versus 79 regions with (68)Ga-DOTATOC (not significant). Overall, however, significantly fewer lesions were detected with (68)Ga-DOTATATE than with (68)Ga-DOTATOC (254 vs. 262, P < 0.05). Mean (68)Ga DOTATATE SUVmax across all lesions was significantly lower than (68)Ga-DOTATOC (16.0 +/- 10.8 vs. 20.4 +/- 14.7, P < 0.01). Mean SUVmax for renal parenchyma was not significantly different between (68)Ga-DOTATATE and (68)Ga-DOTATOC (12.7 +/- 3.0 vs. 13.2 +/- 3.3). CONCLUSION: (68)Ga-DOTATOC and (68)Ga-DOTATATE possess a comparable diagnostic accuracy for the detection of NET lesions, with (68)Ga DOTATOC having a potential advantage. The approximately 10-fold higher affinity for the sst2 of (68)Ga-DOTATATE does not prove to be clinically relevant. Quite unexpectedly, SUVmax of (68)Ga-DOTATOC scans tended to be higher than their (68)Ga-DOTATATE counterparts. PMID- 22072705 TI - PET of aromatase in gastric parietal cells using 11C-vorozole. AB - Aromatase is a rate-limiting enzyme for estrogen biosynthesis and has been implicated in pathophysiological states of various diseases via estrogen production. This enzyme is known to be widely distributed in extragonadal and gonadal tissues including the stomach. In contrast to circulating estrogen, the functional role of gastric aromatase/estrogen has not been elucidated in detail, because there is no efficient methodology to investigate spatiotemporal changes of gastric aromatase/estrogen in vivo. Recently, (S)-(11)C-6-[(4-chlorophenyl)(1H 1,2,4-triazole-1-yl)methyl]-1-methyl-1H-benzotriazole ((11)C-labeled vorozole), based on a potent nonsteroidal aromatase inhibitor, has been developed as a tracer to investigate aromatase distribution in living animals and humans using a noninvasive PET technique. In the present study, we investigated gastric aromatase expression by means of PET with (11)C-vorozole. METHODS: After bolus injection of (11)C-vorozole into the tail vein, emission scans were obtained for 90 min on male and female rats under isoflurane anesthesia. Displacement studies with unlabeled vorozole and autoradiographic analysis were conducted for demonstration of specific binding. Immunohistochemistry was performed to confirm aromatase expression. RESULTS: PET scans revealed that (11)C-vorozole highly accumulated in the stomach and adrenal glands. Displacement studies and autoradiography demonstrated that aromatase was expressed in the stomach but that the accumulation of (11)C-vorozole in the adrenal glands might be through nonspecific binding. Immunohistochemical analysis revealed that aromatase is expressed in gastric parietal cells but not in adrenal glands. Moreover, the accumulation of (11)C-vorozole in the stomach was significantly increased in fatigued rats. CONCLUSION: These results suggest that the (11)C-vorozole PET technique is a useful tool for evaluation of gastric aromatase dynamics in vivo, which may provide important information for understanding the molecular mechanisms of gastric aromatase/estrogen-related pathophysiological processes and for the development of new drugs. PMID- 22072706 TI - PET with the 89Zr-labeled transforming growth factor-beta antibody fresolimumab in tumor models. AB - Transforming growth factor-beta (TGF-beta) promotes cancer invasion and metastasis and is therefore a potential drug target for cancer treatment. Fresolimumab, which neutralizes all mammalian active isoforms of TGF-beta, was radiolabeled with (89)Zr for PET to analyze TGF-beta expression, antibody tumor uptake, and organ distribution. METHODS: (89)Zr was conjugated to fresolimumab using the chelator N-succinyldesferrioxamine-B-tetrafluorphenol. (89)Zr fresolimumab was analyzed for conjugation ratio, aggregation, radiochemical purity, stability, and immunoreactivity. (89)Zr-fresolimumab tumor uptake and organ distribution were assessed using 3 protein doses (10, 50, and 100 MUg) and compared with (111)In-IgG in a human TGF-beta-transfected Chinese hamster ovary xenograft model, human breast cancer MDA-MB-231 xenograft, and metastatic model. Latent and active TGF-beta1 expression was analyzed in tissue homogenates with enzyme-linked immunosorbent assay. RESULTS: (89)Zr was labeled to fresolimumab with high specific activity (>1 GBq/mg), high yield, and high purity. In vitro validation of (89)Zr-fresolimumab showed a fully preserved immunoreactivity and long (>1 wk) stability in solution and in human serum. In vivo validation showed an (89)Zr-fresolimumab distribution similar to IgG in most organs, except for a higher uptake in the liver in all mice and higher kidney uptake in the 10-MUg group. (89)Zr-fresolimumab induced no toxicity in mice; it accumulated in primary tumors and metastases in a manner similar to IgG. Both latent and active TGF-beta was detected in tumor homogenates, whereas only latent TGF-beta could be detected in liver homogenates. Remarkably high (89)Zr-fresolimumab uptake was seen in sites of tumor ulceration and in scar tissue, processes in which TGF-beta is known to be highly active. CONCLUSION: Fresolimumab tumor uptake and organ distribution can be visualized and quantified with (89)Zr-fresolimumab PET. This technique will be used to guide further clinical development of fresolimumab and could possibly identify patients most likely to benefit. PMID- 22072707 TI - Oxidized LDL promotes the mitogenic actions of Chlamydia pneumoniae in vascular smooth muscle cells. AB - AIMS: The atherogenic actions of Chlamydia pneumoniae (C. pneumoniae), a common respiratory pathogen, are dependent upon a high-cholesterol environment in vivo. It is possible that oxidized low-density lipoprotein (oxLDL) is responsible for promoting the atherogenic effects of C. pneumoniae through a stimulation of cell proliferation. This study determined whether oxLDL can enhance the mitogenic action of C. pneumoniae in vascular smooth muscle cells (VSMCs) and the involvement of mitogen-activated protein kinase (MAPK) pathways and heat shock protein 60 (HSP60) in these mechanisms. METHODS AND RESULTS: Primary rabbit VSMCs were treated with live C. pneumoniae, heat-inactivated C. pneumoniae or infection medium, and subsequently incubated for up to 48 h in the presence or absence of oxLDL. Chlamydia pneumoniae infection alone stimulated cell proliferation and the addition of oxLDL significantly amplified this proliferative effect. This proliferation was accompanied by extracellular signal-regulated kinase-1 and -2 (ERK1/2) activation and an up-regulation of HSP60 expression. Changes in proliferation and HSP60 expression were attenuated by the inhibition of ERK1/2. CONCLUSION: These results indicate a novel role for oxLDL in promoting the mitogenic actions of C. pneumoniae in the vasculature. ERK1/2 is an important factor in the stress-mediated response and HSP60 up-regulation in VSMC. These data provide mechanistic evidence that C. pneumoniae may stimulate atherogenesis. PMID- 22072708 TI - Terminal amino acids disturb xylanase thermostability and activity. AB - Protein structure is composed of regular secondary structural elements (alpha helix and beta-strand) and non-regular region. Unlike the helix and strand, the non-regular region consists of an amino acid defined as a disordered residue (DR). When compared with the effect of the helix and strand, the effect of the DR on enzyme structure and function is elusive. An Aspergillus niger GH10 xylanase (Xyn) was selected as a model molecule of (beta/alpha)(8) because the general structure consists of ~10% enzymes. The Xyn has five N-terminal DRs and one C terminal DR, respectively, which were deleted to construct three mutants, XynDeltaN, XynDeltaC, and XynDeltaNC. Each mutant was ~2-, 3-, or 4-fold more thermostable and 7-, 4-, or 4-fold more active than the Xyn. The N-terminal deletion decreased the xylanase temperature optimum for activity (T(opt)) 6 degrees C, but the C-terminal deletion increased its T(opt) 6 degrees C. The N- and C-terminal deletions had opposing effects on the enzyme T(opt) but had additive effects on its thermostability. The five N-terminal DR deletions had more effect on the enzyme kinetics but less effect on its thermo property than the one C-terminal DR deletion. CD data showed that the terminal DR deletions increased regular secondary structural contents, and hence, led to slow decreased Gibbs free energy changes (DeltaG(0)) in the thermal denaturation process, which ultimately enhanced enzyme thermostabilities. PMID- 22072709 TI - Quality control of fungus-specific glucosylceramide in Cryptococcus neoformans by endoglycoceramidase-related protein 1 (EGCrP1). AB - A fungus-specific glucosylceramide (GlcCer), which contains a unique sphingoid base possessing two double bonds and a methyl substitution, is essential for pathogenicity in fungi. Although the biosynthetic pathway of the GlcCer has been well elucidated, little is known about GlcCer catabolism because a GlcCer degrading enzyme (glucocerebrosidase) has yet to be identified in fungi. We found a homologue of endoglycoceramidase tentatively designated endoglycoceramidase related protein 1 (EGCrP1) in several fungal genomic databases. The recombinant EGCrP1 hydrolyzed GlcCer but not other glycosphingolipids, whereas endoglycoceramidase hydrolyzed oligosaccharide-linked glycosphingolipids but not GlcCer. Disruption of egcrp1 in Cryptococcus neoformans, a typical pathogenic fungus causing cryptococcosis, resulted in the accumulation of fungus-specific GlcCer and immature GlcCer that possess sphingoid bases without a methyl substitution concomitant with a dysfunction of polysaccharide capsule formation. These results indicated that EGCrP1 participates in the catabolism of GlcCer and especially functions to eliminate immature GlcCer in vivo that are generated as by-products due to the broad specificity of GlcCer synthase. We conclude that EGCrP1, a glucocerebrosidase identified for the first time in fungi, controls the quality of GlcCer by eliminating immature GlcCer incorrectly generated in C. neoformans, leading to accurate processing of fungus-specific GlcCer. PMID- 22072710 TI - HIV-1 Vpu protein antagonizes innate restriction factor BST-2 via lipid-embedded helix-helix interactions. AB - The Vpu protein of HIV-1 antagonizes BST-2 (tetherin), a broad spectrum effector of the innate immune response to viral infection, by an intermolecular interaction that maps genetically to the alpha-helical transmembrane domains (TMDs) of each protein. Here we utilize NMR spectroscopy to describe key features of the helix-helix pairing that underlies this interaction. The antagonism of BST 2 involves a sequence of three alanines and a tryptophan spaced at four residue intervals within the Vpu TMD helix. Responsiveness to Vpu involves bulky hydrophobic residues in the C-terminal region of the BST-2 TMD helix that likely fit between the alanines on the interactive face of Vpu. These aspects of Vpu and BST-2 form an anti-parallel, lipid-embedded helix-helix interface. Changes in human BST-2 that mimic sequences found in nonhuman primate orthologs unresponsive to Vpu change the tilt angle of the TMD in the lipid bilayer without abrogating its intrinsic ability to interact with Vpu. These data explain the mechanism by which HIV-1 evades a key aspect of innate immunity and the species specificity of Vpu using an anti-parallel helix-helix packing model. PMID- 22072711 TI - Polarity-regulating kinase partitioning-defective 1b (PAR1b) phosphorylates guanine nucleotide exchange factor H1 (GEF-H1) to regulate RhoA-dependent actin cytoskeletal reorganization. AB - Partitioning-defective 1b (PAR1b), also known as microtubule affinity-regulating kinase 2 (MARK2), is a member of evolutionally conserved PAR1/MARK serine/threonine kinase family, which plays a key role in the establishment and maintenance of cell polarity at least partly by phosphorylating microtubule associated proteins (MAPs) that regulate microtubule stability. PAR1b has also been reported to influence actin cytoskeletal organization, raising the possibility that PAR1b functionally interacts with the Rho family of small GTPases, central regulators of the actin cytoskeletal system. Consistent with this notion, PAR1 was recently found to be physically associated with a RhoA specific guanine nucleotide exchange factor H1 (GEF-H1). This observation suggests a functional link between PAR1b and GEF-H1. Here we show that PAR1b induces phosphorylation of GEF-H1 on serine 885 and serine 959. We also show that PAR1b-induced serine 885/serine 959 phosphorylation inhibits RhoA-specific GEF activity of GEF-H1. As a consequence, GEF-H1 phosphorylated on both of the serine residues loses the ability to stimulate RhoA and thereby fails to induce RhoA dependent stress fiber formation. These findings indicate that PAR1b not only regulates microtubule stability through phosphorylation of MAPs but also influences actin stress fiber formation by inducing GEF-H1 phosphorylation. The dual function of PAR1b in the microtubule-based cytoskeletal system and the actin based cytoskeletal system in the coordinated regulation of cell polarity, cell morphology, and cell movement. PMID- 22072712 TI - Unifying concept of serotonin transporter-associated currents. AB - Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter associated currents. PMID- 22072714 TI - Loss of the methyl lysine effector protein PHF20 impacts the expression of genes regulated by the lysine acetyltransferase MOF. AB - In epigenetic signaling pathways, histone tails are heavily modified, resulting in the recruitment of effector molecules that can influence transcription. One such molecule, plant homeodomain finger protein 20 (PHF20), uses a Tudor domain to read dimethyl lysine residues and is a known component of the MOF (male absent on the first) histone acetyltransferase protein complex, suggesting it plays a role in the cross-talk between lysine methylation and histone acetylation. We sought to investigate the biological role of PHF20 by generating a knockout mouse. Without PHF20, mice die shortly after birth and display a wide variety of phenotypes within the skeletal and hematopoietic systems. Mechanistically, PHF20 is not required for maintaining the global H4K16 acetylation levels or locus specific histone acetylation but instead works downstream in transcriptional regulation of MOF target genes. PMID- 22072713 TI - SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid beta protein oligomerization and memory loss in mouse model of Alzheimer disease. AB - Oxidative stress is closely linked to the pathogenesis of neurodegeneration. Soluble amyloid beta (Abeta) oligomers cause cognitive impairment and synaptic dysfunction in Alzheimer disease (AD). However, the relationship between oligomers, oxidative stress, and their localization during disease progression is uncertain. Our previous study demonstrated that mice deficient in cytoplasmic copper/zinc superoxide dismutase (CuZn-SOD, SOD1) have features of drusen formation, a hallmark of age-related macular degeneration (Imamura, Y., Noda, S., Hashizume, K., Shinoda, K., Yamaguchi, M., Uchiyama, S., Shimizu, T., Mizushima, Y., Shirasawa, T., and Tsubota, K. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 11282-11287). Amyloid assembly has been implicated as a common mechanism of plaque and drusen formation. Here, we show that Sod1 deficiency in an amyloid precursor protein-overexpressing mouse model (AD mouse, Tg2576) accelerated Abeta oligomerization and memory impairment as compared with control AD mouse and that these phenomena were basically mediated by oxidative damage. The increased plaque and neuronal inflammation were accompanied by the generation of N(epsilon) carboxymethyl lysine in advanced glycation end products, a rapid marker of oxidative damage, induced by Sod1 gene-dependent reduction. The Sod1 deletion also caused Tau phosphorylation and the lower levels of synaptophysin. Furthermore, the levels of SOD1 were significantly decreased in human AD patients rather than non-AD age-matched individuals, but mitochondrial SOD (Mn-SOD, SOD2) and extracellular SOD (CuZn-SOD, SOD3) were not. These findings suggest that cytoplasmic superoxide radical plays a critical role in the pathogenesis of AD. Activation of Sod1 may be a therapeutic strategy for the inhibition of AD progression. PMID- 22072715 TI - PPARdelta coordinates angiotensin II-induced senescence in vascular smooth muscle cells through PTEN-mediated inhibition of superoxide generation. AB - Cellular senescence-associated changes in blood vessels have been implicated in aging and age-related cardiovascular disorders. Here, we demonstrate that peroxisome proliferator-activated receptor (PPAR) delta coordinates angiotensin (Ang) II-induced senescence of human vascular smooth muscle cells (VSMCs). Activation of PPARdelta by GW501516, a specific ligand for PPARdelta, significantly attenuated Ang II-induced generation of superoxides and suppressed senescence of VSMCs. A marked increase in the levels of p53 and p21 induced by Ang II was blunted by the treatment with GW501516. Ligand-activated PPARdelta up regulated expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and suppressed the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Knockdown of PTEN with siRNA abrogated the effects of PPARdelta on cellular senescence, on PI3K/Akt signaling, and on generation of ROS in VSMCs treated with Ang II. Finally, administration of GW501516 to apoE-deficient mice treated with Ang II significantly reduced the number of senescent cells in the aorta, where up regulation of PTEN with reduced levels of phosphorylated Akt and ROS was demonstrated. Thus, ligand-activated PPARdelta confers resistance to Ang II induced senescence by up-regulation of PTEN and ensuing modulation of the PI3K/Akt signaling to reduce ROS generation in vascular cells. PMID- 22072716 TI - Protein-linked ubiquitin chain structure restricts activity of deubiquitinating enzymes. AB - The attachment of lysine 48 (Lys(48))-linked polyubiquitin chains to proteins is a universal signal for degradation by the proteasome. Here, we report that long Lys(48)-linked chains are resistant to many deubiquitinating enzymes (DUBs). Representative enzymes from this group, Ubp15 from yeast and its human ortholog USP7, rapidly remove mono- and diubiquitin from substrates but are slow to remove longer Lys(48)-linked chains. This resistance is lost if the structure of Lys(48) linked chains is disrupted by mutation of ubiquitin or if chains are linked through Lys(63). In contrast to Ubp15 and USP7, Ubp12 readily cleaves the ends of long chains, regardless of chain structure. We propose that the resistance to many DUBs of long, substrate-attached Lys(48)-linked chains helps ensure that proteins are maintained free from ubiquitin until a threshold of ubiquitin ligase activity enables degradation. PMID- 22072717 TI - Pharmacologic uncoupling of angiogenesis and inflammation during initiation of pathological corneal neovascularization. AB - Pathological neovascularization occurs when a balance of pro- and anti-angiogenic factors is disrupted, accompanied by an amplifying inflammatory cascade. However, the interdependence of these responses and the mechanism triggering the initial angiogenic switch have remained unclear. We present data from an epithelial debridement model of corneal neovascularization describing an initial 3-day period when a substantial component of neovascular growth occurs. Administration of selective inhibitors shows that this initial growth requires signaling through VEGFR-2 (vascular endothelial growth factor receptor-2), independent of the accompanying inflammatory response. Instead, increased VEGF production is found prominently in repair epithelial cells and is increased prior to recruitment of neutrophil/granulocytes and macrophage/monocytes. Consequently, early granulocyte and monocyte depletion has little effect on corneal neovascularization outgrowth. These data indicate that it is possible to pharmacologically uncouple these mechanisms during early injury-driven neovascularization in the cornea and suggest that initial tissue responses are coordinated by repair epithelial cells. PMID- 22072718 TI - Inhibitor of Nrf2 (INrf2 or Keap1) protein degrades Bcl-xL via phosphoglycerate mutase 5 and controls cellular apoptosis. AB - INrf2 (Keap1) is an adaptor protein that facilitates INrf2-Cul3-Rbx1-mediated ubiquitination/degradation of Nrf2, a master regulator of cytoprotective gene expression. Here, we present evidence that members of the phosphoglycerate mutase family 5 (PGAM5) proteins are involved in the INrf2-mediated ubiquitination/degradation of anti-apoptotic factor Bcl-xL. Mass spectrometry and co-immunoprecipitation assays revealed that INrf2, through its DGR domain, interacts with PGAM5, which in turn interacts with anti-apoptotic Bcl-xL protein. INrf2-Cul3-Rbx1 complex facilitates ubiquitination and degradation of both PGAM5 and Bcl-xL. Overexpression of PGAM5 protein increased INrf2-mediated degradation of Bcl-xL, whereas knocking down PGAM5 by siRNA decreased INrf2 degradation of Bcl-xL, resulting in increased stability of Bcl-xL. Mutation of PGMA5-E79A/S80A abolished INrf2/PGAM5/Bcl-xL interaction. Therefore, PGAM5 protein acts as a bridge between INrf2 and Bcl-xL interaction. Further studies showed that overexpression of INrf2 enhanced degradation of PGAM5-Bcl-xL complex, led to etoposide-mediated accumulation of Bax, increased release of cytochrome c from mitochondria, activated caspase-3/7, and enhanced DNA fragmentation and apoptosis. In addition, antioxidant (tert-butylhydroquinone) treatment destabilized the Nrf2-INrf2-PGAM5-Bcl-xL complex, which resulted in release of Nrf2 in cytosol and mitochondria, release of Bcl-xL in mitochondria, increase in Bcl-xL heterodimerization with Bax in mitochondria, and reduced cellular apoptosis. These data provide the first evidence that INrf2 controls Bcl-xL via PGAM5 and controls cellular apoptosis. PMID- 22072719 TI - Phosphorylation of PhoP protein plays direct regulatory role in lipid biosynthesis of Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis PhoP is essential for virulence and intracellular growth of the tubercle bacilli. Genetic evidence suggests that PhoP regulates complex lipid biosynthesis, and absence of some of these lipid molecules in a phoP mutant partly accounts for its attenuated growth in macrophages and/or mice. To investigate the mechanism of regulation, here we demonstrate the essentiality of phosphorylation of PhoP in the regulation of complex lipid biosynthesis. We show that phosphorylated PhoP activates transcription of pks2 and msl3, gene(s) encoding polyketide beta-ketoacyl synthases through direct DNA binding at the upstream regulatory region(s) of the target genes. Our results identify the genetic determinants recognized by PhoP and show that activation of target genes requires interaction(s) of the phosphorylated regulator at the cognate binding sites. The fact that these sites within the regulatory region of respective genes do not bind in vitro with either unphosphorylated or phosphorylation-deficient PhoP protein is consistent with phosphorylation-dependent assembly of the transcription initiation complex leading to in vivo transcriptional activation. Together, these results reveal so far unknown molecular mechanisms of how PhoP contributes to M. tuberculosis cell wall composition by regulating complex lipid biosynthesis. PMID- 22072721 TI - Long-term antibody and immune memory response induced by pulmonary delivery of the influenza Iscomatrix vaccine. AB - Pulmonary delivery of an influenza Iscomatrix adjuvant vaccine induces a strong systemic and mucosal antibody response. Since an influenza vaccine needs to induce immunological memory that lasts at least 1 year for utility in humans, we examined the longevity of the immune response induced by such a pulmonary vaccination, with and without antigen challenge. Sheep were vaccinated in the deep lung with an influenza Iscomatrix vaccine, and serum and lung antibody levels were quantified for up to 1 year. The immune memory response to these vaccinations was determined following antigen challenge via lung delivery of influenza antigen at 6 months and 1 year postvaccination. Pulmonary vaccination of sheep with the influenza Iscomatrix vaccine induced antigen-specific antibodies in both sera and lungs that were detectable until 6 months postimmunization. Importantly, a memory recall response following antigenic challenge was detected at 12 months post-lung vaccination, including the induction of functional antibodies with hemagglutination inhibition activity. Pulmonary delivery of an influenza Iscomatrix vaccine induces a long-lived influenza virus-specific antibody and memory response of suitable length for annual vaccination against influenza. PMID- 22072720 TI - Vaccines displaying mycobacterial proteins on biopolyester beads stimulate cellular immunity and induce protection against tuberculosis. AB - New improved vaccines are needed for control of both bovine and human tuberculosis. Tuberculosis protein vaccines have advantages with regard to safety and ease of manufacture, but efficacy against tuberculosis has been difficult to achieve. Protective cellular immune responses can be preferentially induced when antigens are displayed on small particles. In this study, Escherichia coli and Lactococcus lactis were engineered to produce spherical polyhydroxybutyrate (PHB) inclusions which displayed a fusion protein of Mycobacterium tuberculosis, antigen 85A (Ag85A)-early secreted antigenic target 6-kDa protein (ESAT-6). L. lactis was chosen as a possible production host due its extensive use in the food industry and reduced risk of lipopolysaccharide contamination. Mice were vaccinated with PHB bead vaccines with or without displaying Ag85A-ESAT-6, recombinant Ag85A-ESAT-6, or M. bovis BCG. Separate groups of mice were used to measure immune responses and assess protection against an aerosol M. bovis challenge. Increased amounts of antigen-specific gamma interferon, interleukin 17A (IL-17A), IL-6, and tumor necrosis factor alpha were produced from splenocytes postvaccination, but no or minimal IL-4, IL-5, or IL-10 was produced, indicating Th1- and Th17-biased T cell responses. Decreased lung bacterial counts and less extensive foci of inflammation were observed in lungs of mice receiving BCG or PHB bead vaccines displaying Ag85A-ESAT-6 produced in either E. coli or L. lactis compared to those observed in the lungs of phosphate-buffered saline treated control mice. No differences between those receiving wild-type PHB beads and those receiving recombinant Ag85A-ESAT-6 were observed. This versatile particulate vaccine delivery system incorporates a relatively simple production process using safe bacteria, and the results show that it is an effective delivery system for a tuberculosis protein vaccine. PMID- 22072722 TI - Persistence and titer changes of rubella virus antibodies in primiparous women who had been vaccinated with strain RA 27/3 in junior high school. AB - Taiwan's rubella vaccination program was launched in 1986; each schoolgirl in the third grade of junior high school received one dose of rubella (RA 27/3) vaccine. We reviewed the results of 14,090 prenatal rubella tests for primiparas from three areas of Taiwan during 2002 to 2008 to investigate seronegativity rates and titer changes. In all primiparous women, the average rubella virus seronegativity rate was 6.5% (95% confidence interval [95% CI], 6.1 to 6.9%), and the average rubella virus antibody titer was 65.9 IU/ml (95% CI, 64.7 to 67.1 IU/ml). There were 1,220 women (8.7%) with weakly positive antibody titers (10 to 20 IU/ml). The rubella virus seronegativity rates, which ranged from 5.4 to 9.7%, did not exhibit a linear trend from 9 to 22 years after vaccination (P = 0.201); in contrast, a significant trend appeared in the average rubella virus IgG titer (P = 0.003), dropping from 69.9 IU/ml in the 9th year after vaccination to 54.8 IU/ml in the 22nd year. The mean annual antibody decay rate was -0.77 IU/ml. This study reveals that the level of rubella virus antibodies declined slowly in women of childbearing age who were vaccinated with RA 27/3 at junior high school age. The number of women who were seronegative or had weakly positive antibody titers was still high (15.2%). Therefore, in countries that implement a single-dose regimen in children or teenagers, it should remain an important policy to encourage voluntary immunization in seronegative women and to immunize all postpartum women who are susceptible to rubella virus infection before they leave the hospital. PMID- 22072723 TI - The nonstructural protein NSs induces a variable antibody response in domestic ruminants naturally infected with Rift Valley fever virus. AB - Rift Valley fever (RVF) is an emerging zoonosis in Africa which has spread to Egypt, the Arabian Peninsula, Madagascar, and Comoros. RVF virus (RVFV) (Bunyaviridae family, Phlebovirus genus) causes a wide range of symptoms in humans, from benign fever to fatal hemorrhagic fever. Ruminants are severely affected by the disease, which leads to a high rate of mortality in young animals and to abortions and teratogenesis in pregnant females. Diagnostic tests include virus isolation and genome or antibody detection. During RVFV infection, the nucleoprotein encapsidating the tripartite RNA genome is expressed in large amounts and raises a robust antibody response, while the envelope glycoproteins elicit neutralizing antibodies which play a major role in protection. Much less is known about the antigenicity/immunogenicity of the nonstructural protein NSs, which is a major virulence factor. Here we have developed a competitive enzyme linked immunosorbent assay (ELISA) enabling detection of low levels of NSs specific antibodies in naturally infected or vaccinated ruminants. Detection of the NSs antibodies was validated by Western blotting. Altogether, our data showed that the NSs antibodies were detected in only 55% of animals naturally infected by RVFV, indicating that NSs does not induce a consistently high immune response. These results are discussed in light of differentiation between infected and vaccinated animals (DIVA) tests distinguishing naturally infected animals and those vaccinated with NSs-defective vaccines. PMID- 22072724 TI - Association of serotype-specific antibody concentrations and functional antibody titers with subsequent pneumococcal carriage in toddlers immunized with a 9 valent pneumococcal conjugate vaccine. AB - Association of pneumococcal nasopharyngeal carriage with the concentration and opsonophagocytic activity (OPA) of serum serotype-specific antibodies was determined for toddlers 1 month after immunization with a 9-valent pneumococcal conjugate vaccine. Higher anti-serotype 14 and anti-serotype 19F IgG and anti serotype 14 IgM correlated with a lowered probability of pneumococcal acquisition. Postvaccination OPA did not correlate with pneumococcal carriage. PMID- 22072726 TI - Eye- and feature-based modulation of onset rivalry caused by the preceding stimulus. AB - Pre-exposure to a stimulus can modulate initial perceptual dominance experienced in binocular rivalry with brief test stimuli (onset rivalry). This study investigated this modulating effect using both color and pattern stimuli. We confirmed separate contributions of eye- and feature-based suppressions and showed that their relative strength varied with temporal parameters. Eye-based suppression was stronger with a short test duration (10 ms) and shorter ISIs between the preceding and test stimuli. On the other hand, feature-based suppression grew with ISI and was more pronounced with a longer test duration (200 ms). We also investigated the nature of the modulating effect associated with feature-based suppression using chromatic gratings of high luminance contrast. Results revealed that different features of the preceding stimulus (i.e., color and orientation) exerted nearly independent effects on onset rivalry. However, different features shared their fate in competitive interactions for perceptual dominance; when one feature became dominant, the other also dominated. These findings suggest that competitive interactions for perceptual dominance and the modulation of these interactions are mediated at least partially by different mechanisms. Overall, the present findings are consistent with a theoretical view that initial dominance is established through competitive interactions at multiple levels of processing. PMID- 22072727 TI - Attention alters decision criteria but not appearance: a reanalysis of Anton Erxleben, Abrams, and Carrasco (2010). AB - Paying attention to a stimulus affords it many behavioral advantages, but whether attention also changes its subjective appearance is controversial. K. A. Schneider and M. Komlos (2008) demonstrated that the results of previous studies suggesting that attention increased perceived contrast could also be explained by a biased decision mechanism. This bias could be neutralized by altering the methodology to ask subjects whether two stimuli were equal in contrast or not rather than which had the higher contrast. K. Anton-Erxleben, J. Abrams, and M. Carrasco (2010) claimed that, even using this equality judgment, attention could still be shown to increase perceived contrast. In this reply, we analyze their data and conclude that the effects that they reported resulted from fitting symmetric functions that poorly characterized the individual subject data, which exhibited significant asymmetries between the high- and low-contrast tails. The strength of the effect attributed to attentional enhancement in each subject was strongly correlated with this skew. By refitting the data with a response model that included a non-zero asymptotic response in the low-contrast regime, we show that the reported attentional effects are better explained as changes in subjective criteria. Thus, the conclusion of Schneider and Komlos that attention biases the decision mechanism but does not alter appearance is still valid and is in fact supported by the data from Anton-Erxleben et al. PMID- 22072728 TI - Equality judgments cannot distinguish between attention effects on appearance and criterion: a reply to Schneider (2011). AB - Whether attention modulates the appearance of stimulus features is debated. Whereas many previous studies using a comparative judgment have found evidence for such an effect, two recent studies using an equality judgment have not. Critically, these studies have relied on the assumption that the equality paradigm yields bias-free PSE estimates and is as sensitive as the comparative judgment, without testing these assumptions. Anton-Erxleben, Abrams, and Carrasco (2010) compared comparative judgments and equality judgments with and without the manipulation of attention. They demonstrated that the equality paradigm is less sensitive than the comparative judgment and also bias-prone. Furthermore, they reported an effect of attention on the PSE using both paradigms. Schneider (2011) questions the validity of the latter finding, stating that the data in the equality experiment are corrupted because of skew in the response distributions. Notably, this argument supports the original conclusion by Anton-Erxleben et al.: that the equality paradigm is bias-prone. Additionally, the necessary analyses to show that the attention effect observed in Anton-Erxleben et al. was due to skew in the data were not conducted. Here, we provide these analyses and show that although the equality judgment is bias-prone, the effects we observe are consistent with an increase of apparent contrast by attention. PMID- 22072729 TI - Race-specific norms for coding face identity and a functional role for norms. AB - Models of face perception often adopt a framework in which faces are represented as points or vectors in a multidimensional space, relative to the average face that serves as a norm for encoding. Since faces are very similar in their configuration and share many visual properties, they could be encoded in one common space against one norm. However, certain face properties may result in grouping and "subclassification" of similar faces. We studied the processing of faces of different races, using high-level aftereffects, where exposure to one face systematically distorts the perception of a subsequently viewed face toward the "opposite" identity in face space. We measured identity aftereffects for adapt-test pairs that were opposite relative to race-specific (Asian and Caucasian) averages and pairs that were opposite relative to a "generic" average (both races morphed together). Aftereffects were larger for race-specific compared to mixed-race adapt-test pairs. These results suggest that race-specific norms are used to code identity because aftereffects are generally larger for adapt-test pairs drawn from trajectories passing through the norm (opposite pairs) than for those that do not. We also found that identification thresholds were lower when targets were distributed around race-specific averages than around the mixed-race average, suggesting that norm-based face encoding may play a functional role in facilitating identity discrimination. PMID- 22072730 TI - Unseen complex motion is modulated by attention and generates a visible aftereffect. AB - The relationship between attention and awareness and the processing of visual information outside of attention and awareness remain controversial issues. We employed the motion aftereffect (MAE) illusion and continuous flash suppression (CFS) to study the behavioral effects of unseen and unattended visual motion. The main finding was that either withdrawal of attention or the lack of visual awareness on the adaptors did not eliminate the formation of translational MAEs, spiral MAEs, or the interocular transfer of the MAE. However, no spiral MAE was generated when attention was diverted from the unseen spiral adaptors. Interestingly, all MAEs that arose in the absence of awareness or in the absence of attention were reduced in size. The pattern of results is consistent with suggestions that the magnitude of visual motion adaptation depends on both attention and awareness. PMID- 22072731 TI - Competitive inhibition of the luminal efflux by multidrug and toxin extrusions, but not basolateral uptake by organic cation transporter 2, is the likely mechanism underlying the pharmacokinetic drug-drug interactions caused by cimetidine in the kidney. AB - Cimetidine, an H2 receptor antagonist, has been used to investigate the tubular secretion of organic cations in human kidney. We report a systematic comprehensive analysis of the inhibition potency of cimetidine for the influx and efflux transporters of organic cations [human organic cation transporter 1 (hOCT1) and hOCT2 and human multidrug and toxin extrusion 1 (hMATE1) and hMATE2 K, respectively]. Inhibition constants (K(i)) of cimetidine were determined by using five substrates [tetraethylammonium (TEA), metformin, 1-methyl-4 phenylpyridinium, 4-(4-(dimethylamino)styryl)-N-methylpyridinium, and m iodobenzylguanidine]. They were 95 to 146 MUM for hOCT2, providing at most 10% inhibition based on its clinically reported plasma unbound concentrations (3.6 7.8 MUM). In contrast, cimetidine is a potent inhibitor of MATE1 and MATE2-K with K(i) values (MUM) of 1.1 to 3.8 and 2.1 to 6.9, respectively. The same tendency was observed for mouse Oct1 (mOct1), mOct2, and mouse Mate1. Cimetidine showed a negligible effect on the uptake of metformin by mouse kidney slices at 20 MUM. Cimetidine was administered to mice by a constant infusion to achieve a plasma unbound concentration of 21.6 MUM to examine its effect on the renal disposition of Mate1 probes (metformin, TEA, and cephalexin) in vivo. The kidney- and liver to-plasma ratios of metformin both were increased 2.4-fold by cimetidine, whereas the renal clearance was not changed. Cimetidine also increased the kidney-to plasma ratio of TEA and cephalexin 8.0- and 3.3-fold compared with a control and decreased the renal clearance from 49 to 23 and 11 to 6.6 ml/min/kg, respectively. These results suggest that the inhibition of MATEs, but not OCT2, is a likely mechanism underlying the drug-drug interactions with cimetidine in renal elimination. PMID- 22072732 TI - The TM2 6' position of GABA(A) receptors mediates alcohol inhibition. AB - Ionotropic GABA(A) receptors (GABA(A)Rs), which mediate inhibitory neurotransmission in the central nervous system, are implicated in the behavioral effects of alcohol and alcoholism. Site-directed mutagenesis studies support the presence of discrete molecular sites involved in alcohol enhancement and, more recently, inhibition of GABA(A)Rs. We used Xenopus laevis oocytes to investigate the 6' position in the second transmembrane region of GABA(A)Rs as a site influencing alcohol inhibition. We asked whether modification of the 6' position by substitution with larger residues or methanethiol labeling [using methyl methanethiosulfonate (MMTS)] of a substituted cysteine, reduced GABA action and/or blocked further inhibition by alcohols. Labeling of the 6' position in either alpha2 or beta2 subunits reduced responses to GABA. In addition, methanol and ethanol potentiation increased after MMTS labeling or substitution with tryptophan or methionine, consistent with elimination of an inhibitory site for these alcohols. Specific alcohols, but not the anesthetic etomidate, competed with MMTS labeling at the 6' position. We verified a role for the 6' position in previously tested alpha2beta2 as well as more physiologically relevant alpha2beta2gamma2s GABA(A)Rs. Finally, we built a novel molecular model based on the invertebrate glutamate-gated chloride channel receptor, a GABA(A)R homolog, revealing that the 6' position residue faces the channel pore, and modification of this residue alters volume and polarity of the pore-facing cavity in this region. These results indicate that the 6' positions in both alpha2 and beta2 GABA(A)R subunits mediate inhibition by short-chain alcohols, which is consistent with the presence of multiple counteracting sites of action for alcohols on ligand-gated ion channels. PMID- 22072733 TI - Leflunomide induces apoptosis in fludarabine-resistant and clinically refractory CLL cells. AB - PURPOSE: Environmental conditions in lymph node proliferation centers protect chronic lymphocytic leukemia (CLL) cells from apoptotic triggers. This situation can be mimicked by in vitro stimulation with CD40 ligand (CD40L) and interleukin 4 (IL-4). Our study investigates the impact of the drug leflunomide to overcome apoptosis resistance of CLL cells. EXPERIMENTAL DESIGN: CLL cells were stimulated with CD40L and IL-4 and treated with fludarabine and the leflunomide metabolite A771726. RESULTS: Resistance to fludarabine-mediated apoptosis was induced by CD40 activation alone stimulating high levels of BCL-XL and MCL1 protein expression. Apoptosis resistance was further enhanced by a complementary Janus activated kinase (JAK)/STAT signal induced by IL-4. In contrast, CLL proliferation required both a CD40 and a JAK/STAT signal and could be completely blocked by pan-JAK inhibition. Leflunomide (A771726) antagonized CD40L/IL-4 induced proliferation at very low concentrations (3 MUg/mL) reported to inhibit dihydroorotate dehydrogenase. At a concentration of 10 MUg/mL, A771726 additionally attenuated STAT3/6 phosphorylation, whereas apoptosis of CD40L/IL-4 activated ("resistant") CLL cells was achieved with higher concentrations (IC(50): 80 MUg/mL). Apoptosis was also effectively induced by A771726 in clinically refractory CLL cells with and without a defective p53 pathway. Induction of apoptosis involved inhibition of NF-kappaB activity and loss of BCL XL and MCL1 expression. In combination with fludarabine, A771726 synergistically induced apoptosis (IC(50): 56 MUg/mL). CONCLUSION: We thus show that A771726 overcomes CD40L/IL-4-mediated resistance to fludarabine in CLL cells of untreated as well as clinically refractory CLL cells. We present a possible novel therapeutic principle for attacking chemoresistant CLL cells. PMID- 22072734 TI - The importance of doing trials right while doing the right trials. AB - Effort is being expended in investigating efficiency measures (i.e., doing trials right) through achievement of accrual and endpoint goals for clinical trials. It is time to assess the impact of such trials on meeting the critical needs of cancer patients by establishing effectiveness measures (i.e., doing the right trials). PMID- 22072736 TI - Increased activation of the PI3K/AKT pathway compromises decidualization of stromal cells from endometriosis. AB - CONTEXT: Endometriosis affects approximately 10% of women in the United States and causes pain and infertility. Decidualization of endometrial stromal cells from women with endometriosis is aberrant. OBJECTIVE: The objective of this study was to investigate a potential mechanism for the inadequate decidual response in stromal cells from ovarian endometriomas. DESIGN: Stromal cells of the endometrium from women without endometriosis (HSC) or from ovarian endometriomas (OsisSC) were grown in culture and treated with 10 MUm LY294002 or 250 nm MK2206, 100 nm medroxyprogesterone acetate (M), and 0.5 mm dibutyryl cAMP (A) or infection with 100 multiplicity of infection adenoviral constructs containing wild-type Forkhead box O1 or triple-mutant FOXO1. Real-time PCR was used to measure the expression of FOXO1, IGF binding protein-1 (IGFBP1), and prolactin (PRL) mRNA, and Western blot and immunohistochemical staining were used to detect the levels of progesterone receptor (PR), FOXO1, AKT, and p(Ser473)-AKT protein in vitro or in vivo. RESULTS: Expression of the decidua-specific genes, IGFBP1 and PRL, were significantly lower in OsisSC compared with normal HSC in response to M+A treatment. Basal expression levels of PRA, PRB, and FOXO1 proteins were dramatically lower in OsisSC. Overexpression of triple-mutant FOXO1 increased mRNA levels of IGFBP1 and PRL in OsisSC in the presence of M+A, whereas the overexpression of wild-type FOXO1 had no effect. AKT was highly phosphorylated in OsisSC compared with HSC and inhibition of phosphatidylinositol 3-kinase, with LY294002, increased levels of FOXO1 protein as well as IGFBP1 mRNA in the presence of M+A. Moreover, inhibition of AKT with MK2206, an allosteric AKT inhibitor, dramatically increased the accumulation of nuclear FOXO1 as well as expression of IGFBP1. Finally, immunohistochemical staining demonstrated higher p(Ser473)-AKT and lower FOXO1 levels in endometriosis tissues, compared with normal endometrial tissues. CONCLUSIONS: In endometriotic stromal cells, overactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway contributes to the reduced expression of the decidua-specific gene, IGFBP1, potentially through reduced levels of nuclear FOXO1. PMID- 22072737 TI - The syndrome of 17,20 lyase deficiency. AB - CONTEXT: Disorders of steroidogenesis have been instrumental in delineating human steroidogenic pathways. Each genetic disorder seemed to correspond to a different steroidogenic activity, helping to identify several enzymes. Beginning in 1972, several patients have been reported as having "17,20 lyase deficiency," but there have been inconsistent genetic findings. OBJECTIVE: This manuscript reviews the biochemistry, genetics, and clinical disorders of 17,20 lyase activity, which converts 21-carbon precursors of glucocorticoids to 19-carbon precursors of sex steroids. FINDINGS: A single enzyme, cytochrome P450c17, catalyzes both 17alpha hydroxylase activity and 17,20 lyase activity. The 17,20 lyase activity is especially sensitive to the activities of the accessory proteins P450 oxidoreductase and cytochrome b(5). The first cases of genetically and biochemically proven 17,20 lyase deficiency were reported in 1997, in which specific P450c17 mutations were identified that lost 17,20 lyase activity but not 17alpha-hydroxylase activity when assayed in vitro. Subsequent work identified other P450c17 mutations and mutations in the genes encoding P450 oxidoreductase and cytochrome b(5). Recently, the initially reported cases from 1972 were found to carry mutations in two aldo-keto reductases, AKR1C2 and AKR1C4. These AKR1C isozymes catalyze 3alpha-hydroxysteroid dehydrogenase activity in the so-called "backdoor pathway" by which the fetal testis produces dihydrotestosterone without the intermediacy of testosterone. CONCLUSIONS: 17,20 Lyase deficiency should be considered a syndrome with multiple causes, and not a single disease. Study of this very rare disorder has substantially advanced our understanding of the pathways, mechanisms, and control of androgen synthesis. Mutations in other, as yet unidentified genes may also cause this phenotype. PMID- 22072738 TI - Vitamin D deficiency in obese children and its relationship to glucose homeostasis. AB - OBJECTIVES: The aim of the study was to compare the prevalence of vitamin D deficiency in obese and non-overweight children in North Texas, to examine relationships between dietary habits and 25-hydroxyvitamin D [25(OH)D] level in obese children, and to examine the relationship between 25(OH)D level and markers of abnormal glucose metabolism and blood pressure. PATIENTS AND METHODS: Using a cross-sectional design, systolic and diastolic blood pressure, dietary information, serum 25(OH)D, fasting glucose and insulin, 2-h glucose from oral glucose tolerance test, hemoglobin A1c, and homeostasis model assessment of insulin resistance were recorded for 411 obese subjects (6-16 yr old) at an obesity referral clinic. 25(OH)D was also obtained from 87 control non-overweight subjects (6-16 yr old). RESULTS: Ninety-two percent of obese subjects had a 25(OH)D level below 75 nmol/liter, and 50% were below 50 nmol/liter. Among non overweight subjects, these frequencies were 68 and 22%, respectively (both P < 0.01 compared with obese subjects). 25(OH)D was negatively associated with soda intake (P < 0.001), juice intake (P = 0.009), and skipping breakfast (P < 0.001). 25(OH)D was negatively correlated with homeostasis model assessment of insulin resistance (r = -0.19; P = 0.001) and 2-h glucose (r = -0.12; P = 0.04) after adjustment for body mass index and age but was not correlated with hemoglobin A1c, systolic blood pressure Z score, or diastolic blood pressure Z score. CONCLUSIONS: Vitamin D deficiency is common in children in this southern United States location and is significantly more prevalent in obese children. Lower 25(OH)D level is associated with risk factors for type 2 diabetes in obese children. PMID- 22072739 TI - Diabetes and femoral neck strength: findings from the Hip Strength Across the Menopausal Transition Study. AB - CONTEXT: Diabetes mellitus is associated with increased hip fracture risk, despite being associated with higher bone mineral density in the femoral neck. OBJECTIVE: The objective of the study was to test the hypothesis that composite indices of femoral neck strength, which integrate dual-energy x-ray absorptiometry derived femoral neck size, femoral neck areal bone mineral density, and body size and are inversely associated with hip fracture risk, would be lower in diabetics than in nondiabetics and be inversely related to insulin resistance, the primary pathology in type 2 diabetes. DESIGN: This was a cross sectional analysis. SETTING AND PARTICIPANTS: The study consisted of a multisite, multiethnic, community-dwelling sample of 1887 women in pre- or early perimenopause. OUTCOME MEASUREMENTS: Composite indices for femoral neck strength in different failure modes (axial compression, bending, and impact) were measured. RESULTS: Adjusted for age, race/ethnicity, menopausal stage, body mass index, smoking, physical activity, calcium and vitamin D supplementation, and study site, diabetic women had higher femoral neck areal bone mineral density [+0.25 sd, 95% confidence interval (CI) (+0.06, +0.44) sd] but lower composite strength indices [-0.20 sd, 95% CI (-0.38, -0.03) sd for compression, -0.19 sd, 95% CI (-0.38, -0.003) sd for bending, -0.19 sd, 95% CI (-0.37, -0.02) sd for impact] than nondiabetic women. There were graded inverse relationships between homeostasis model-assessed insulin resistance and all three strength indices, adjusted for the same covariates. CONCLUSIONS: Despite having higher bone density, diabetic women have lower indices of femoral neck strength relative to load, consistent with their documented higher fracture risk. Insulin resistance appears to play an important role in bone strength reduction in diabetes. PMID- 22072740 TI - Olfactory phenotypic spectrum in idiopathic hypogonadotropic hypogonadism: pathophysiological and genetic implications. AB - CONTEXT: The olfactory phenotype in patients with idiopathic hypogonadotropic hypogonadism (IHH) ranges from complete anosmia (Kallmann syndrome) to normosmia (normosmic IHH). However, the true prevalence of intermediary olfactory phenotypes (hyposmia) in IHH patients has not yet been assessed, and systematic correlations with anatomical and genetic abnormalities have not been reported. OBJECTIVE: The objective of this study was to evaluate olfactory function in a large IHH cohort and correlate these findings with olfactory magnetic resonance imaging (MRI) and underlying genetic etiology. DESIGN AND SETTING: We conducted a cross-sectional case-control study at an academic referral center. PATIENTS: A total of 286 IHH patients (201 males and 85 females) and 2183 healthy historic controls (1011 males and 1172 females) were studied. MAIN OUTCOME MEASURES: We measured olfactory function using the University of Pennsylvania Smell Identification Test; in 208 subjects, the genetic etiology of IHH was ascertained by DNA sequencing; in a minor subset [39 of 286 subjects (13%)], olfactory structures were determined by MRI. RESULTS: In the IHH cohort, 31.5% were anosmic, 33.6% were hyposmic, and 34.9% were normosmic. Most hyposmic (seven of 11) subjects with MRI data exhibited olfactory structure abnormalities. Of hyposmic subjects, 39.5% harbored mutations in genes involved in either GnRH neuronal migration or GnRH secretion. CONCLUSIONS: IHH subjects display a broad spectrum of olfactory function, with a significant hyposmic phenotype in nearly one third of subjects. The hyposmic subjects harbor mutations in genes affecting GnRH neuronal migration and its secretion, suggesting a pathophysiological overlap between Kallmann syndrome and normosmic IHH. Accurate olfactory phenotyping in IHH subjects will inform the pathophysiology of this condition and guide genetic testing. PMID- 22072741 TI - Low-dose zoledronate in osteopenic postmenopausal women: a randomized controlled trial. AB - CONTEXT: Annual iv administration of 5 mg zoledronate decreases fracture risk. The skeletal effects of annual treatment with doses of zoledronate under 4 mg have not been assessed. OBJECTIVE: Our objective was to determine the skeletal effects of single doses of zoledronate of 5 mg or less. DESIGN, SETTING, AND PARTICIPANTS: This was a double-blind, randomized, placebo-controlled trial over 1 yr at an academic research center in 180 postmenopausal women with osteopenia. INTERVENTION: Intervention was a single baseline administration of iv zoledronate in doses of 1, 2.5, or 5 mg, or placebo. MAIN OUTCOME MEASURES: The primary endpoint was change in bone mineral density (BMD) at the lumbar spine. Secondary endpoints were change in BMD at the proximal femur and total body and changes in biochemical markers of bone turnover. RESULTS: After 12 months, change in spine BMD was greater in each of the zoledronate groups than in the placebo group [mean (95% confidence interval) difference vs. placebo was 3.5% (2.2-4.8%) for 1 mg, 4.0% (2.7-5.3%) for 2.5 mg, and 3.6% (2.3-4.9%) for 5 mg zoledronate, P < 0.001 for each dose]. Change in BMD at the total hip was greater in each of the zoledronate groups than the placebo group [mean (95% confidence interval) difference vs. placebo was 2.7% (1.9-3.5%) for 1 mg, 3.6% (2.8-4.4%) for 2.5 mg, and 3.6% (2.8-4.4%) for 5 mg zoledronate, P < 0.001 for each dose]. Each of the bone turnover markers, beta-C-terminal telopeptide of type I collagen and procollagen type I N-terminal propeptide, was lower by at least 40% in each of the zoledronate groups than the placebo group throughout the trial (P < 0.001 vs. placebo for each marker for each dose). There was evidence for a dose-dependent effect of zoledronate on each of the markers (P for trend <0.001). CONCLUSION: Annual administration of doses of iv zoledronate lower than 5 mg produces substantial antiresorptive effects. Trials assessing the antifracture efficacy of low doses of zoledronate are justified. PMID- 22072742 TI - Pioglitazone-mediated changes in lipoprotein particle composition are predicted by changes in adiponectin level in type 2 diabetes. AB - CONTEXT: In animal and observational studies, adiponectin is associated with lipoprotein risk factors for cardiovascular disease. OBJECTIVE: We analyzed data from a randomized clinical trial to evaluate the relationship between changes in adiponectin to changes in lipoprotein risk factors after an intervention that alters adiponectin levels. DESIGN AND SETTING: Adiponectin levels were measured at baseline and follow-up, as were lipoprotein risk factors for cardiovascular disease, at academic medical centers and ambulatory care centers. PATIENTS AND OTHER PARTICIPANTS: Participants included 361 men and women with type 2 diabetes. INTERVENTION: Intervention included randomization to treatment with glimepiride or pioglitazone for 72 wk. MAIN OUTCOME MEASURE: The relationship of treatment related differences in adiponectin level to treatment-related differences in lipoprotein cardiovascular risk factors at 72 wk was evaluated. RESULTS: Pioglitazone led to an increase in adiponectin compared with glimepiride. Compared with baseline, pioglitazone treatment at 72 wk led to an increase in low density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size and a decrease in very-low-density lipoprotein (VLDL) particle size and LDL particle number. Glimepiride treatment more modestly decreased LDL particle number and increased LDL particle size. At 72 wk, there were significant treatment group differences for HDL, LDL, and VLDL particle size, and triglyceride and HDL cholesterol level. The increase in adiponectin predicted treatment-related improvement for triglyceride and HDL cholesterol level and LDL and HDL particle size. CONCLUSION: Increased adiponectin contributed to treatment-related benefit in lipoprotein cardiovascular disease risk factors in obese diabetic subjects treated with pioglitazone. These results provide support for a model that mechanistically links changes in adiponectin level to changes in lipoprotein composition in humans. PMID- 22072743 TI - BAG3 down-modulation reduces anaplastic thyroid tumor growth by enhancing proteasome-mediated degradation of BRAF protein. AB - CONTEXT: Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms. OBJECTIVE: The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth. DESIGN AND SUBJECTS: We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome dependent mechanism. RESULTS: BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132. CONCLUSION: BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins. PMID- 22072744 TI - For protection from HIV-1 infection, more might not be better: a systematic analysis of HIV Gag epitopes of two alleles associated with different outcomes of HIV-1 infection. AB - A subset of women in the Pumwani Sex Worker Cohort, established in 1985 in Nairobi, Kenya, remains uninfected despite repeated high-risk exposure (HIV exposed, seronegative [HESN]) through active sex work. This HESN phenotype is associated with several alleles of human leukocyte antigens (HLAs) and specific CD8(+) and CD4(+) T cell responses to HIV-1. The associations of HLA alleles with differential HIV-1 infection are most likely due to their different abilities to present antigen and the different immune responses they induce. The characteristics of epitopes of HLA alleles associated with different outcomes of HIV-1 infection might therefore point to a vital clue for developing an effective vaccine. In this study, we systematically analyzed HIV-1 clade A and D Gag CD8(+) T cell epitopes of two HLA class I alleles associated with different outcomes of HIV-1 infection. Binding affinity and off-rates of the identified epitopes were determined. Gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISpot) assays with patient peripheral blood mononuclear cells (PBMCs) validated the epitopes. Epitope-specific CD8(+) T cells were further phenotyped for memory markers with tetramer staining. Our study showed that the protective allele A*01:01 recognizes only three Gag epitopes. By contrast, B*07:02, the allele associated with susceptibility, binds 30 epitope variants. These two alleles differ most importantly in the spectrum of Gag epitopes they can present and not in affinity, off-rates, the location of the epitopes, or epitope-specific Tem/Tcm frequencies. The binding of more epitopes and strong IFN-gamma ELISpot responses are associated with susceptibility to HIV-1 infection, while more focused antigen recognition of multiple subtypes is protective. Rational vaccine design should take these observations into account. PMID- 22072745 TI - Direct interaction of baculovirus capsid proteins VP39 and EXON0 with kinesin-1 in insect cells determined by fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy. AB - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) replicates in the nucleus of insect cells to produce nucleocapsids, which are transported from the nucleus to the plasma membrane for budding through GP64-enriched areas to form budded viruses. However, little is known about the anterograde trafficking of baculovirus nucleocapsids in insect cells. Preliminary confocal scanning laser microscopy studies showed that enhanced green fluorescent protein (EGFP)-tagged nucleocapsids and capsid proteins aligned and colocalized with the peripheral microtubules of virus-infected insect cells. A colchicine inhibition assay of virus-infected insect cells showed a significant reduction in budded virus production, providing further evidence for the involvement of microtubules and suggesting a possible role of kinesin in baculovirus anterograde trafficking. We investigated the interaction between AcMNPV nucleocapsids and kinesin-1 with fluorescence resonance energy transfer-fluorescence lifetime imaging microscopy (FRET-FLIM) and show for the first time that AcMNPV capsid proteins VP39 and EXON0, but not Orf1629, interact with the tetratricopeptide repeat (TPR) domain of kinesin. The excited-state fluorescence lifetime of EGFP fused to VP39 or EXON0 was quenched from 2.4 +/- 1 ns to 2.1 +/- 1 ns by monomeric fluorescent protein (mDsRed) fused to TPR (mDsRed-TPR). However, the excited-state fluorescence lifetime of an EGFP fusion of Orf1629 remained unquenched by mDsRed TPR. These data indicate that kinesin-1 plays an important role in the anterograde trafficking of baculovirus in insect cells. PMID- 22072746 TI - Adenovirus serotype 5-specific neutralizing antibodies target multiple hexon hypervariable regions. AB - The immunogenicity of adenovirus serotype 5 (Ad5) vectors has been shown to be suppressed by neutralizing antibodies (NAbs) directed primarily against the hexon hypervariable regions (HVRs). We previously reported that replacing all seven HVRs with those from the rare serotype virus Ad48 resulted in a chimeric Ad5HVR48(1-7) vector that largely evaded preexisting Ad5 immunity in mice and rhesus monkeys. In this study, we evaluated the extent to which Ad5-specific NAbs are directed against various HVRs. We constructed partial HVR-chimeric Ad5 vectors with only a subset of HVRs exchanged, and we utilized these vectors in both NAb assays and murine immunogenicity studies with and without baseline Ad5 immunity. Our results demonstrate that Ad5-specific NAbs target multiple HVRs, suggesting that replacing all HVRs is required to optimize evasion of anti-Ad5 immunity. These data have important implications for the development of novel vectors for both vaccines and gene therapy. PMID- 22072747 TI - Cross-species transmission of simian foamy virus to humans in rural Gabon, Central Africa. AB - In order to characterize simian foamy retroviruses (SFVs) in wild-born nonhuman primates (NHPs) in Gabon and to investigate cross-species transmission to humans, we obtained 497 NHP samples, composed of 286 blood and 211 tissue (bush meat) samples. Anti-SFV antibodies were found in 31 of 286 plasma samples (10.5%). The integrase gene sequence was found in 38/497 samples, including both blood and tissue samples, with novel SFVs in several Cercopithecus species. Of the 78 humans, mostly hunters, who had been bitten or scratched by NHPs, 19 were SFV seropositive, with 15 cases confirmed by PCR. All but one were infected with ape SFV. We thus found novel SFV strains in NHPs in Gabon and high cross-species transmission of SFVs from gorilla bites. PMID- 22072748 TI - Measles virus C protein interferes with Beta interferon transcription in the nucleus. AB - Transcriptional induction of beta interferon (IFN-beta) through pattern recognition receptors is a key event in the host defense against invading viruses. Infection of cells by paramyxoviruses, like measles virus (MV) (genus Morbillivirus), is sensed predominantly by the ubiquitous cytoplasmic helicase RIG-I, recognizing viral 5'-triphosphate RNAs, and to some degree by MDA5. While MDA5 activation is effectively prevented by the MV V protein, the viral mechanisms for inhibition of MDA5-independent induction of IFN-beta remained obscure. Here, we identify the 186-amino-acid MV C protein, which shuttles between the nucleus and the cytoplasm, as a major viral inhibitor of IFN-beta transcription in human cells. Activation of the transcription factor IRF3 by upstream kinases and nuclear import of activated IRF3 were not affected in the presence of C protein, suggesting a nuclear target. Notably, C proteins of wild type MV isolates, which are poor IFN-beta inducers, were found to comprise a canonical nuclear localization signal (NLS), whereas the NLSs of all vaccine strains, irrespective of their origins, were mutated. Site-directed mutagenesis of the C proteins from an MV wild-type isolate and from the vaccine virus strain Schwarz confirmed a correlation of nuclear localization and inhibition of IFN beta transcription. A functional NLS and efficient nuclear accumulation are therefore critical for MV C to retain its potential to downregulate IFN-beta induction. We suggest that a defect in efficient nuclear import of C protein contributes to attenuation of MV vaccine strains. PMID- 22072749 TI - Evidence against extracellular exposure of a highly immunogenic region in the C terminal domain of the simian immunodeficiency virus gp41 transmembrane protein. AB - The generally accepted model for human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein topology includes a single membrane-spanning domain. An alternate model has been proposed which features multiple membrane-spanning domains. Consistent with the alternate model, a high percentage of HIV-1-infected individuals produce unusually robust antibody responses to a region of envelope, the so-called "Kennedy epitope," that in the conventional model should be in the cytoplasm. Here we show analogous, robust antibody responses in simian immunodeficiency virus SIVmac239-infected rhesus macaques to a region of SIVmac239 envelope located in the C-terminal domain, which in the conventional model should be inside the cell. Sera from SIV-infected rhesus macaques consistently reacted with overlapping oligopeptides corresponding to a region located within the cytoplasmic domain of gp41 by the generally accepted model, at intensities comparable to those observed for immunodominant areas of the surface component gp120. Rabbit serum raised against this highly immunogenic region (HIR) reacted with SIV envelope in cell surface-staining experiments, as did monoclonal anti-HIR antibodies isolated from an SIVmac239-infected rhesus macaque. However, control experiments demonstrated that this surface staining could be explained in whole or in part by the release of envelope protein from expressing cells into the supernatant and the subsequent attachment to the surfaces of cells in the culture. Serum and monoclonal antibodies directed against the HIR failed to neutralize even the highly neutralization-sensitive strain SIVmac316. Furthermore, a potential N-linked glycosylation site located close to the HIR and postulated to be outside the cell in the alternate model was not glycosylated. An artificially introduced glycosylation site within the HIR was also not utilized for glycosylation. Together, these data support the conventional model of SIV envelope as a type Ia transmembrane protein with a single membrane-spanning domain and without any extracellular loops. PMID- 22072750 TI - Covariation of major and minor viral capsid proteins in norovirus genogroup II genotype 4 strains. AB - We report sequence hypervariability in the viral protein 1 (VP1) interaction domain of VP2 in the norovirus (NoV) genogroup II genotype 4 (GII.4) lineage on 3 levels: (i) the global evolution of pandemic/epidemic strains from the mid-1970s through post-2006, (ii) the local emergence of an epidemic strain, and (iii) an immunocompromised patient chronically shedding NoV. When a quantitative yeast two hybrid assay was used, VP2 was found to interact with VP1 in a time-ordered, strain-dependent manner among 3 NoV GII.4 strains. Our findings suggest that VP1 and VP2 may covary in virus evolution and that sequence hypervariability of VP2 may be functionally driven. Further investigations are warranted. PMID- 22072751 TI - IkappaB kinase epsilon-dependent phosphorylation and degradation of X-linked inhibitor of apoptosis sensitizes cells to virus-induced apoptosis. AB - X-linked inhibitor of apoptosis (XIAP) is a potent antagonist of caspase 3-, 7-, and 9-dependent apoptotic activities that functions as an E3 ubiquitin ligase, and it targets caspases for degradation. In this study, we demonstrate that Sendai virus (SeV) infection results in the IKKepsilon- or TBK1-mediated phosphorylation of XIAP in vivo at Ser430, resulting in Lys(48)-linked autoubiquitination at Lys322/328 residues, followed by the subsequent proteasomal degradation of XIAP. Interestingly, IKKepsilon expression and XIAP turnover increases SeV-triggered mitochondrion-dependent apoptosis via the release of caspase 3, whereas TBK1 expression does not increase apoptosis. Interestingly, phosphorylation also regulates XIAP interaction with the transcription factor IRF3, suggesting a role in IRF3-Bax-mediated apoptosis. Our findings reveal a novel function of IKKepsilon as a regulator of the virus-induced triggering of apoptosis via the phosphorylation-dependent turnover of XIAP. PMID- 22072752 TI - Combination of PB2 271A and SR polymorphism at positions 590/591 is critical for viral replication and virulence of swine influenza virus in cultured cells and in vivo. AB - Triple reassortant swine influenza viruses (SIVs) and 2009 pandemic H1N1 (pH1N1) virus contain an avian-origin PB2 with 271A, 590S, 591R, and 627E. To evaluate the role of PB2 271A, 590S, and 591R in the replication and virulence of SIV, single (1930-TX98-PB2-271T)-, double (1930-TX98-PB2-590A591A)-, and triple (1930 TX98-PB2-271T590A591A)-mutated viruses were generated in the background of the H1N1 A/swine/Iowa/15/30 (1930) virus with an avian-origin PB2 from the triple reassortant A/swine/Texas/4199-2/98 (TX98) virus, called the parental 1930-TX98 PB2. Compared to parental virus and single- and double-mutated viruses, the triple-mutated virus replicated less efficiently in cell cultures and was attenuated in mice. These results suggest that a combination of 271A with the 590/591 SR polymorphism is critical for pH1N1 and triple-reassortant SIVs for efficient replication and adaptation in mammals. PMID- 22072753 TI - Polyfunctional T cells accumulate in large human cytomegalovirus-specific T cell responses. AB - Large cytomegalovirus (CMV)-specific CD8 T-cell responses are observed in both young and, somewhat more often, old people. Frequent CMV reactivation is thought to exhaust these cells and render them dysfunctional so that larger numbers of them are needed to control CMV. Expansions of CMV-specific CD4 T cells are also seen but are less well studied. In this study, we examined the T-cell response to the dominant CMV pp65 and IE-1 antigens in healthy CMV-infected people across a wide age range (20 to 84 years) by using multicolor flow cytometry. CMV-specific T cells were characterized by the activation markers CD40 ligand (CD40L), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) and the memory markers CD27 and CD45RA. The proportions of effector memory T cells increased in large responses, as did the proportions of polyfunctional CD8 (IFN-gamma(+) IL-2(+/-) TNF-alpha(+)) and CD4 (CD40L(+/-) IFN gamma(+) IL-2(+) TNF-alpha(+)) T-cell subsets, while the proportion of naive T cells decreased. The bigger the CD4 or CD8 T-cell response to pp65, the larger was the proportion of T cells with an advanced memory phenotype in the entire (including non-CMV-specific) T-cell compartment. In addition, the number of activation markers per cell correlated with the degree of T-cell receptor downregulation, suggesting increased antigen sensitivity in polyfunctional cells. In summary, our findings show that polyfunctional CMV-specific T cells were not superseded by dysfunctional cells, even in very large responses. At the same time, however, the memory subset composition of the entire T-cell compartment correlated with the size of the T-cell response to CMV pp65, confirming a strong effect of CMV infection on the immune systems of some, but not all, infected people. PMID- 22072754 TI - Structural map of a microRNA-122: hepatitis C virus complex. AB - MicroRNA-122 (miR-122) enhances hepatitis C virus (HCV) fitness via targeting two sites in the 5'-untranslated region (UTR) of HCV. We used selective 2'-hydroxyl acylation analyzed by primer extension to resolve the HCV 5'-UTR's RNA secondary structure in the presence of miR-122. Nearly all nucleotides in miR-122 are involved in targeting the second site, beyond classic seed base pairings. These additional interactions enhance HCV replication in cell culture. To our knowledge, this is the first biophysical study of this complex to reveal the importance of 'tail' miR-122 nucleotide interactions. PMID- 22072755 TI - Viral adaptation to host immune responses occurs in chronic hepatitis B virus (HBV) infection, and adaptation is greatest in HBV e antigen-negative disease. AB - Hepatitis B virus (HBV)-specific T-cell responses are important in the natural history of HBV infection. The number of known HBV-specific T-cell epitopes is limited, and it is not clear whether viral evolution occurs in chronic HBV infection. We aimed to identify novel HBV T-cell epitopes by examining the relationship between HBV sequence variation and the human leukocyte antigen (HLA) type in a large prospective clinic-based cohort of Asian patients with chronic HBV infection recruited in Australia and China (n = 119). High-resolution 4-digit HLA class I and II typing and full-length HBV sequencing were undertaken for treatment-naive individuals (52% with genotype B, 48% with genotype C, 63% HBV e antigen [HBeAg] positive). Statistically significant associations between HLA types and HBV sequence variation were identified (n = 49) at 41 sites in the HBV genome. Using prediction programs, we determined scores for binding between peptides containing these polymorphisms and associated HLA types. Among the regions that could be tested, HLA binding was predicted for 14/18 (78%). We identified several HLA-associated polymorphisms involving likely known anchor residues that resulted in altered predicted binding scores. Some HLA-associated polymorphisms fell within known T-cell epitopes with matching HLA restriction. Enhanced viral adaptation (defined as the presence of the relevant HLA and the escaped amino acid) was independently associated with HBeAg-negative disease (P = 0.003). Thus, HBV appears to be under immune pressure in chronic HBV infection, particularly in HBeAg-negative disease. PMID- 22072756 TI - Chicken cells sense influenza A virus infection through MDA5 and CARDIF signaling involving LGP2. AB - Avian influenza viruses (AIV) raise worldwide veterinary and public health concerns due to their potential for zoonotic transmission. While infection with highly pathogenic AIV results in high mortality in chickens, this is not necessarily the case in wild birds and ducks. It is known that innate immune factors can contribute to the outcome of infection. In this context, retinoic acid-inducible gene I (RIG-I) is the main cytosolic pattern recognition receptor known for detecting influenza A virus infection in mammalian cells. Chickens, unlike ducks, lack RIG-I, yet chicken cells do produce type I interferon (IFN) in response to AIV infection. Consequently, we sought to identify the cytosolic recognition elements in chicken cells. Chicken mRNA encoding the putative chicken analogs of CARDIF and LGP2 (chCARDIF and chLGP2, respectively) were identified. HT7-tagged chCARDIF was observed to associate with mitochondria in chicken DF-1 fibroblasts. The exogenous expression of chCARDIF, as well as of the caspase activation and recruitment domains (CARDs) of the chicken melanoma differentiation-associated protein 5 (chMDA5), strongly activated the chicken IFN beta (chIFN-beta) promoter. The silencing of chMDA5, chCARDIF, and chIRF3 reduced chIFN-beta levels induced by AIV, indicating their involvement in AIV sensing. As with mammalian cells, chLGP2 had opposing effects. While overexpression decreased the activation of the chIFN-beta promoter, the silencing of endogenous chLGP2 reduced chIFN-beta induced by AIV. We finally demonstrate that the chMDA5 signaling pathway is inhibited by the viral nonstructural protein 1. In conclusion, chicken cells, including DF-1 fibroblasts and HD-11 macrophage-like cells, employ chMDA5 for sensing AIV. PMID- 22072757 TI - Activation of NF-kappaB in CD8+ dendritic cells Ex Vivo by the gamma134.5 null mutant correlates with immunity against herpes simplex virus 1. AB - The gamma(1)34.5 protein of herpes simplex viruses (HSV) is essential for virulence. Accordingly, an HSV mutant lacking gamma(1)34.5 is attenuated in vivo. Despite its vaccine potential, the mechanism by which the gamma(1)34.5 null mutant triggers protective immunity is unknown. In this report we show that vaccination with the gamma(1)34.5 null mutant protects against lethal challenge from wild-type virus via IkappaB kinase in dendritic cells (DCs), which sense virus-associated molecular patterns. Unlike mock-treated DCs, DCs primed with the gamma(1)34.5 null mutant ex vivo mediate resistance to wild-type HSV after adoptive transfer into naive mice. Furthermore, the gamma(1)34.5 null mutant activates IkappaB kinase, which facilitates p65/RelA phosphorylation and nuclear translocation, resulting in DC maturation. While unable to produce infectious virus in DCs, this mutant virus expresses early and late genes. In its abortive infection, the gamma(1)34.5 null mutant induces protective immunity more effectively in CD8(+) DCs than in CD8(-) DCs. This is mirrored by a higher level of interleukin-6 (IL-6) and IL-12 secretion by CD8(+) DCs than CD8(-) DCs. Remarkably, inhibition of p65/RelA phosphorylation or nuclear translocation in CD8(+) DCs disrupts protective immunity. These results suggest that engagement of the gamma(1)34.5 null mutant with CD8(+) DCs elicits innate immunity to activate NF-kappaB, which translates into protective immunity. PMID- 22072759 TI - Escape from a dominant HLA-B*15-restricted CD8+ T cell response against hepatitis C virus requires compensatory mutations outside the epitope. AB - Antiviral CD8(+) T cells are a key component of the adaptive immune system against hepatitis C virus (HCV). For the development of immune therapies, it is essential to understand how CD8(+) T cells contribute to clearance of infection and why they fail so often. A mechanism for secondary failure is mutational escape of the virus. However, some substitutions in viral epitopes are associated with fitness costs and often require compensatory mutations. We hypothesized that compensatory mutations may point toward epitopes under particularly strong selection pressure that may be beneficial for vaccine design because of a higher genetic barrier to escape. We previously identified two HLA-B*15-restricted CD8(+) epitopes in NS5B (LLRHHNMVY(2450-2458) and SQRQKKVTF(2466-2474)), based on sequence analysis of a large HCV genotype 1b outbreak. Both epitopes are targeted in about 70% of HLA-B*15-positive individuals exposed to HCV. Reproducible selection of escape mutations was confirmed in an independent multicenter cohort in the present study. Interestingly, mutations were also selected in the epitope flanking region, suggesting that compensatory evolution may play a role. Covariation analysis of sequences from the database confirmed a significant association between escape mutations inside one of the epitopes (H2454R and M2456L) and substitutions in the epitope flanking region (S2439T and K2440Q). Functional analysis with the subgenomic replicon Con1 confirmed that the primary escape mutations impaired viral replication, while fitness was restored by the additional substitutions in the epitope flanking region. We concluded that selection of escape mutations inside an HLA-B*15 epitope requires secondary substitutions in the epitope flanking region that compensate for fitness costs. PMID- 22072758 TI - Potent autologous and heterologous neutralizing antibody responses occur in HIV-2 infection across a broad range of infection outcomes. AB - Few studies have explored the role of neutralizing antibody (NAb) responses in controlling HIV-2 viremia and disease progression. Using a TZM-bl neutralization assay, we assessed heterologous and autologous NAb responses from a community cohort of HIV-2-infected individuals with a broad range of disease outcomes in rural Guinea-Bissau. All subjects (n = 40) displayed exceptionally high heterologous NAb titers (50% inhibitory plasma dilution or 50% inhibitory concentration [IC(50)], 1:7,000 to 1:1,000,000) against 5 novel primary HIV-2 envelopes and HIV-2 7312A, whereas ROD A and 3 primary envelopes were relatively resistant to neutralization. Most individuals also showed high autologous NAb against contemporaneous envelopes (78% of plasma-envelope combinations in 69 envelopes from 21 subjects), with IC(50)s above 1:10,000. No association between heterologous or autologous NAb titer and greater control of HIV-2 was found. A subset of envelopes was found to be more resistant to neutralization (by plasma and HIV-2 monoclonal antibodies). These envelopes were isolated from individuals with greater intrapatient sequence diversity and were associated with changes in potential N-linked glycosylation sites but not CD4 independence or CXCR4 use. Plasma collected from up to 15 years previously was able to potently neutralize recent autologous envelopes, suggesting a lack of escape from NAb and the persistence of neutralization-sensitive variants over time, despite significant NAb pressure. We conclude that despite the presence of broad and potent NAb responses in HIV-2-infected individuals, these are not the primary forces behind the dichotomous outcomes observed but reveal a limited capacity for adaptive selection and escape from host immunity in HIV-2 infection. PMID- 22072760 TI - Conserved glycine 33 residue in flexible domain I of hepatitis C virus core protein is critical for virus infectivity. AB - Hepatitis C virus core protein forms the viral nucleocapsid and plays a critical role in the formation of infectious particles. In this study, we demonstrate that the highly conserved residue G33, located within domain 1 of the core protein, is important for the production of cell culture-infectious virus (HCVcc). Alanine substitution at this position in the JFH1 genome did not alter viral RNA replication but reduced infectivity by ~2 logs. Virus production by this core mutant could be rescued by compensatory mutations located immediately upstream and downstream of the original G33A mutation. The examination of the helix-loop helix motif observed in the core protein structure (residues 15 to 41; Protein Data Bank entry 1CWX) indicated that the residues G33 and F24 are in close contact with each other, and that the G33A mutation induces a steric clash with F24. Molecular simulations revealed that the compensatory mutations increase the helix-loop-helix flexibility, allowing rescue of the core active conformation required for efficient virus production. Taken together, these data highlight the plasticity of core domain 1 conformation and illustrate the relationship between its structural tolerance to mutations and virus infectivity. PMID- 22072761 TI - Crystallographic analysis reveals octamerization of viroplasm matrix protein P9-1 of Rice black streaked dwarf virus. AB - The P9-1 protein of Rice black streaked dwarf virus accumulates in viroplasm inclusions, which are structures that appear to play an important role in viral morphogenesis and are commonly found in viruses in the family Reoviridae. Crystallographic analysis of P9-1 revealed structural features that allow the protein to form dimers via hydrophobic interactions. Each dimer has carboxy terminal regions, resembling arms, that extend to neighboring dimers, thereby uniting sets of four dimers via lateral hydrophobic interactions, to yield cylindrical octamers. The importance of these regions for the formation of viroplasm-like inclusions was confirmed by the absence of such inclusions when P9 1 was expressed without its carboxy-terminal arm. The octamers are vertically elongated cylinders resembling the structures formed by NSP2 of rotavirus, even though there are no significant similarities between the respective primary and secondary structures of the two proteins. Our results suggest that an octameric structure with an internal pore might be important for the functioning of the respective proteins in the events that occur in the viroplasm, which might include viral morphogenesis. PMID- 22072762 TI - Uncoupling cis-Acting RNA elements from coding sequences revealed a requirement of the N-terminal region of dengue virus capsid protein in virus particle formation. AB - Little is known about the mechanism of flavivirus genome encapsidation. Here, functional elements of the dengue virus (DENV) capsid (C) protein were investigated. Study of the N-terminal region of DENV C has been limited by the presence of overlapping cis-acting RNA elements within the protein-coding region. To dissociate these two functions, we used a recombinant DENV RNA with a duplication of essential RNA structures outside the C coding sequence. By the use of this system, the highly conserved amino acids FNML, which are encoded in the RNA cyclization sequence 5'CS, were found to be dispensable for C function. In contrast, deletion of the N-terminal 18 amino acids of C impaired DENV particle formation. Two clusters of basic residues (R5-K6-K7-R9 and K17-R18-R20-R22) were identified as important. A systematic mutational analysis indicated that a high density of positive charges, rather than particular residues at specific positions, was necessary. Furthermore, a differential requirement of N-terminal sequences of C for viral particle assembly was observed in mosquito and human cells. While no viral particles were observed in human cells with a virus lacking the first 18 residues of C, DENV propagation was detected in mosquito cells, although to a level about 50-fold less than that observed for a wild-type (WT) virus. We conclude that basic residues at the N terminus of C are necessary for efficient particle formation in mosquito cells but that they are crucial for propagation in human cells. This is the first report demonstrating that the N terminus of C plays a role in DENV particle formation. In addition, our results suggest that this function of C is differentially modulated in different host cells. PMID- 22072763 TI - Role of multiple hosts in the cross-species transmission and emergence of a pandemic parvovirus. AB - Understanding the mechanisms of cross-species virus transmission is critical to anticipating emerging infectious diseases. Canine parvovirus type 2 (CPV-2) emerged as a variant of a feline parvovirus when it acquired mutations that allowed binding to the canine transferrin receptor type 1 (TfR). However, CPV-2 was soon replaced by a variant virus (CPV-2a) that differed in antigenicity and receptor binding. Here we show that the emergence of CPV involved an additional host range variant virus that has circulated undetected in raccoons for at least 24 years, with transfers to and from dogs. Raccoon virus capsids showed little binding to the canine TfR, showed little infection of canine cells, and had altered antigenic structures. Remarkably, in capsid protein (VP2) phylogenies, most raccoon viruses fell as evolutionary intermediates between the CPV-2 and CPV 2a strains, suggesting that passage through raccoons assisted in the evolution of CPV-2a. This highlights the potential role of alternative hosts in viral emergence. PMID- 22072764 TI - Genetic inactivation of COPI coatomer separately inhibits vesicular stomatitis virus entry and gene expression. AB - Viruses coopt cellular membrane transport to invade cells, establish intracellular sites of replication, and release progeny virions. Recent genome wide RNA interference (RNAi) screens revealed that genetically divergent viruses require biosynthetic membrane transport by the COPI coatomer complex for efficient replication. Here we found that disrupting COPI function by RNAi inhibited an early stage of vesicular stomatitis virus (VSV) replication. To dissect which replication stage(s) was affected by coatomer inactivation, we used visual and biochemical assays to independently measure the efficiency of viral entry and gene expression in hamster (ldlF) cells depleted of the temperature sensitive epsilon-COP subunit. We show that epsilon-COP depletion for 12 h caused a primary block to virus internalization and a secondary defect in viral gene expression. Using brefeldin A (BFA), a chemical inhibitor of COPI function, we demonstrate that short-term (1-h) BFA treatments inhibit VSV gene expression, while only long-term (12-h) treatments block virus entry. We conclude that prolonged coatomer inactivation perturbs cellular endocytic transport and thereby indirectly impairs VSV entry. Our results offer an explanation of why COPI coatomer is frequently identified in screens for cellular factors that support cell invasion by microbial pathogens. PMID- 22072765 TI - Human pulmonary microvascular endothelial cells support productive replication of highly pathogenic avian influenza viruses: possible involvement in the pathogenesis of human H5N1 virus infection. AB - Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause sporadic human infections with a high fatality rate. Respiratory failure due to acute respiratory distress syndrome (ARDS) is a complication among hospitalized patients. Since progressive pulmonary endothelial damage is the hallmark of ARDS, we investigated host responses following HPAI virus infection of human pulmonary microvascular endothelial cells. Evaluation of these cells for the presence of receptors preferred by influenza virus demonstrated that avian-like (alpha2-3 linked) receptors were more abundant than human-like (alpha2-6-linked) receptors. To test the permissiveness of pulmonary endothelial cells to virus infection, we compared the replication of selected seasonal, pandemic (2009 H1N1 and 1918), and potentially pandemic (H5N1) influenza virus strains. We observed that these cells support productive replication only of HPAI H5N1 viruses, which preferentially enter through and are released from the apical surface of polarized human endothelial monolayers. Furthermore, A/Thailand/16/2004 and A/Vietnam/1203/2004 (VN/1203) H5N1 viruses, which exhibit heightened virulence in mammalian models, replicated to higher titers than less virulent H5N1 strains. VN/1203 infection caused a significant decrease in endothelial cell proliferation compared to other subtype viruses. VN/1203 virus was also found to be a potent inducer of cytokines and adhesion molecules known to regulate inflammation during acute lung injury. Deletion of the H5 hemagglutinin (HA) multibasic cleavage site did not affect virus infectivity but resulted in decreased virus replication in endothelial cells. Our results highlight remarkable tropism and infectivity of the H5N1 viruses for human pulmonary endothelial cells, resulting in the potent induction of host inflammatory responses. PMID- 22072766 TI - Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue. AB - A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies. PMID- 22072767 TI - Proteomic profiling of the human cytomegalovirus UL35 gene products reveals a role for UL35 in the DNA repair response. AB - Human cytomegalovirus infections involve the extensive modification of host cell pathways, including cell cycle control, the regulation of the DNA damage response, and averting promyelocytic leukemia (PML)-mediated antiviral responses. The UL35 gene from human cytomegalovirus is important for viral gene expression and efficient replication and encodes two proteins, UL35 and UL35a, whose mechanism of action is not well understood. Here, affinity purification coupled with mass spectrometry was used to identify previously unknown human cellular targets of UL35 and UL35a. We demonstrate that both viral proteins interact with the ubiquitin-specific protease USP7, and that UL35 expression can alter USP7 subcellular localization. In addition, UL35 (but not UL35a) was found to associate with three components of the Cul4(DCAF1) E3 ubiquitin ligase complex (DCAF1, DDB1, and DDA1) previously shown to be targeted by the HIV-1 Vpr protein. The coimmunoprecipitation and immunofluorescence microscopy of DCAF1 mutants revealed that the C-terminal region of DCAF1 is required for association with UL35 and mediates the dramatic relocalization of DCAF1 to UL35 nuclear bodies, which also contain conjugated ubiquitin. As previously reported for the Vpr-DCAF1 interaction, UL35 (but not UL35a) expression resulted in the accumulation of cells in the G(2) phase of the cell cycle, which is typical of a DNA damage response, and activated the G(2) checkpoint in a DCAF1-dependent manner. In addition, UL35 (but not UL35a) induced gamma-H2AX and 53BP1 foci, indicating the activation of DNA damage and repair responses. Therefore, the identified interactions suggest that UL35 can contribute to viral replication through the manipulation of host responses. PMID- 22072768 TI - RNA interference against animal viruses: how morbilliviruses generate extended diversity to escape small interfering RNA control. AB - Viruses are serious threats to human and animal health. Vaccines can prevent viral diseases, but few antiviral treatments are available to control evolving infections. Among new antiviral therapies, RNA interference (RNAi) has been the focus of intensive research. However, along with the development of efficient RNAi-based therapeutics comes the risk of emergence of resistant viruses. In this study, we challenged the in vitro propensity of a morbillivirus (peste des petits ruminants virus), a stable RNA virus, to escape the inhibition conferred by single or multiple small interfering RNAs (siRNAs) against conserved regions of the N gene. Except with the combination of three different siRNAs, the virus systematically escaped RNAi after 3 to 20 consecutive passages. The genetic modifications involved consisted of single or multiple point nucleotide mutations and a deletion of a stretch of six nucleotides, illustrating that this virus has an unusual genomic malleability. PMID- 22072769 TI - HIV latency in the humanized BLT mouse. AB - Even after extended treatment with powerful antiretroviral drugs, HIV is not completely eliminated from infected individuals. Latently infected CD4(+) T cells constitute one reservoir of replication-competent HIV that needs to be eliminated to completely purge virus from antiretroviral drug-treated patients. However, a major limitation in the development of therapies to eliminate this latent reservoir is the lack of relevant in vivo models that can be used to test purging strategies. Here, we show that the humanized BLT (bone marrow-liver-thymus) mouse can be used as both an abundant source of primary latently infected cells for ex vivo latency analysis and also as an in vivo system for the study of latency. We demonstrate that over 2% of human cells recovered from the spleens of HIV infected BLT mice can be latently infected and that this virus is integrated, activation inducible, and replication competent. The non-tumor-inducing phorbol esters prostratin and 12-deoxyphorbol-13-phenylacetate can each induce HIV ex vivo from these latently infected cells, indicating that this model can be used as a source of primary cells for testing latency activators. Finally, we show activation-inducible virus is still present following suppression of plasma viral loads to undetectable levels by using the antiretroviral drugs zidovudine, indinavir sulfate, and didanosine, demonstrating that this model can also be used to assess the in vivo efficacy of latency-purging strategies. Therefore, the HIV infected BLT mouse should provide a useful model for assessment of HIV latency activators and approaches to eliminate persistent in vivo HIV reservoirs. PMID- 22072770 TI - Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency. AB - Establishment of persistent Epstein-Barr virus (EBV) infection requires transition from a program of full viral latency gene expression (latency III) to one that is highly restricted (latency I and 0) within memory B lymphocytes. It is well established that DNA methylation plays a critical role in EBV gene silencing, and recently the chromatin boundary protein CTCF has been implicated as a pivotal regulator of latency via its binding to several loci within the EBV genome. One notable site is upstream of the common EBNA gene promoter Cp, at which CTCF may act as an enhancer-blocking factor to initiate and maintain silencing of EBNA gene transcription. It was previously suggested that increased expression of CTCF may underlie its potential to promote restricted latency, and here we also noted elevated levels of DNA methyltransferase 1 (DNMT1) and DNMT3B associated with latency I. Within B-cell lines that maintain latency I, however, stable knockdown of CTCF, DNMT1, or DNMT3B or of DNMT1 and DNMT3B in combination did not result in activation of latency III protein expression or EBNA gene transcription, nor did knockdown of DNMTs significantly alter CpG methylation within Cp. Thus, differential expression of CTCF and DNMT1 and -3B is not critical for maintenance of restricted latency. Finally, mutant EBV lacking the Cp CTCF binding site exhibited sustained Cp activity relative to wild-type EBV in a recently developed B-cell superinfection model but ultimately was able to transition to latency I, suggesting that CTCF contributes to but is not necessarily essential for the establishment of restricted latency. PMID- 22072771 TI - Requirements for mouse mammary tumor virus Rem signal peptide processing and function. AB - Mouse mammary tumor virus (MMTV) encodes a Rev-like protein, Rem, which is involved in the nuclear export and expression of viral RNA. Previous data have shown that all Rev-like functions are localized to the 98-amino-acid signal peptide (SP) at the N terminus of MMTV Rem or envelope proteins. MMTV-SP uses endoplasmic reticulum-associated degradation (ERAD) for protein trafficking. Rem cleavage by signal peptidase in the ER is necessary for MMTV-SP function in a reporter assay, but many requirements for trafficking are not known. To allow detection and localization of both MMTV-SP and the C-terminal cleavage product, we prepared plasmids expressing green fluorescent protein (GFP) tags. N-terminal Rem tagging led to protein accumulation relative to untagged Rem and allowed signal peptidase cleavage but reduced its specific activity. C-terminal tagging also led to Rem accumulation yet dramatically reduced cleavage, GFP fluorescence, and activity relative to N-terminally tagged Rem (GFPRem). Substitutions of an invariant leucine at position 71 between the known RNA-binding and nuclear export sequences interfered with GFPRem accumulation and activity but not cleavage. Similarly, deletion of 100 or 150 C-terminal amino acids from GFPRem dramatically reduced both Rem and MMTV-SP levels and function. Removal of the entire C terminus (203 amino acids) restored both protein levels and activity of MMTV-SP. Only C-terminal GFP tagging, and not other modifications, appeared to trap Rem in the ER membrane. Thus, Rem conformation in both the ER lumen and cytoplasm determines cleavage, retrotranslocation, and MMTV-SP function. These mutants further characterize intermediates in Rem trafficking and have implications for all proteins affected by ERAD. PMID- 22072772 TI - Impact of host proteases on reovirus infection in the respiratory tract. AB - Virion uncoating is an essential early event in reovirus infection. In natural enteric infections, rapid proteolytic uncoating of virions is mediated by pancreatic serine proteases. The proteases that promote reovirus disassembly and cell entry in the respiratory tract remain unknown. In this report, we show that endogenous respiratory and inflammatory proteases can promote reovirus infection in vitro and that preexisting inflammation augments in vivo infection in the murine respiratory tract. PMID- 22072773 TI - Ex vivo and in vivo inhibition of human rhinovirus replication by a new pseudosubstrate of viral 2A protease. AB - Human rhinoviruses (HRVs) remain a significant public health problem as they are the major cause of both upper and lower respiratory tract infections. Unfortunately, to date no vaccine or antiviral against these pathogens is available. Here, using a high-throughput yeast two-hybrid screening, we identified a 6-amino-acid hit peptide, LVLQTM, which acted as a pseudosubstrate of the viral 2A cysteine protease (2A(pro)) and inhibited its activity. This peptide was chemically modified with a reactive electrophilic fluoromethylketone group to form a covalent linkage with the nucleophilic active-site thiol of the enzyme. Ex vivo and in vivo experiments showed that thus converted, LVLQTM was a strong inhibitor of HRV replication in both A549 cells and mice. To our knowledge, this is the first report validating a compound against HRV infection in a mouse model. PMID- 22072774 TI - Arterivirus and nairovirus ovarian tumor domain-containing Deubiquitinases target activated RIG-I to control innate immune signaling. AB - The innate immune response constitutes the first line of defense against viral infection and is extensively regulated through ubiquitination. The removal of ubiquitin from innate immunity signaling factors by deubiquitinating enzymes (DUBs) therefore provides a potential opportunity for viruses to evade this host defense system. It was previously found that specific proteases encoded by the unrelated arteri- and nairoviruses resemble the ovarian tumor domain-containing (OTU) family of DUBs. In arteriviruses, this domain has been characterized before as a papain-like protease (PLP2) that is also involved in replicase polyprotein processing. In nairoviruses, the DUB resides in the polymerase protein but is not essential for RNA replication. Using both in vitro and cell-based assays, we now show that PLP2 DUB activity is conserved in all members of the arterivirus family and that both arteri- and nairovirus DUBs inhibit RIG-I-mediated innate immune signaling when overexpressed. The potential relevance of RIG-I-like receptor (RLR) signaling for the innate immune response against arterivirus infection is supported by our finding that in mouse embryonic fibroblasts, the production of beta interferon primarily depends on the recognition of arterivirus RNA by the pattern-recognition receptor MDA5. Interestingly, we also found that both arteri- and nairovirus DUBs inhibit RIG-I ubiquitination upon overexpression, suggesting that both MDA5 and RIG-I have a role in countering infection by arteriviruses. Taken together, our results support the hypothesis that arteri- and nairoviruses employ their deubiquitinating potential to inactivate cellular proteins involved in RLR-mediated innate immune signaling, as exemplified by the deubiquitination of RIG-I. PMID- 22072776 TI - Adenovirus serotype 5 neutralizing antibodies target both hexon and fiber following vaccination and natural infection. AB - The immunogenicity of adenovirus serotype 5 (Ad5) vectors has been shown to be suppressed by neutralizing antibodies (NAbs) directed primarily against the hexon hypervariable regions (HVRs). However, the role of NAbs directed against other capsid components, particularly the adenovirus fiber, remains unclear. Here we show that Ad5 NAbs target both hexon and fiber following vaccination and natural infection. Utilizing neutralization assays with capsid chimeric vectors, we observed that NAb responses to hexon appeared dominant and NAb responses against fiber were subdominant in sera from vaccinated mice, vaccinated humans, and naturally exposed humans. A novel chimeric Ad5 vector in which both the hexon HVRs and the fiber knob were exchanged nearly completely evaded Ad5-specific NAbs both in vitro and in vivo. PMID- 22072775 TI - Cellular VPS4 is required for efficient entry and egress of budded virions of Autographa californica multiple nucleopolyhedrovirus. AB - Membrane budding is essential for the egress of many enveloped viruses, and this process shares similarities with the biogenesis of multivesicular bodies (MVBs). In eukaryotic cells, the budding of intraluminal vesicles (IVLs) is mediated by the endosomal sorting complex required for transport (ESCRT) machinery and some viruses require ESCRT machinery components or functions to bud from host cells. Baculoviruses, such as Autographa californica multiple nucleopolyhedrovirus (AcMNPV), enter host cells by clathrin-mediated endocytosis. Viral DNA replication and nucleocapsid assembly occur within the nucleus. Some progeny nucleocapsids are subsequently trafficked to, and bud from, the plasma membrane, forming budded virions (BV). To determine whether the host ESCRT machinery is important or necessary for AcMNPV replication, we cloned a cDNA of Spodoptera frugiperda VPS4, a key regulator for disassembly and recycling of ESCRT III. We then examined viral infection and budding in the presence of wild-type (WT) or dominant negative (DN) forms of VPS4. First, we used a viral complementation system, in combination with fluorescent tags, to examine the effects of transiently expressed WT or DN VPS4 on viral entry. We found that dominant negative VPS4 substantially inhibited virus entry. Entering virus was observed within aberrant compartments containing the DN VPS4 protein. We next used recombinant bacmids expressing WT or DN VPS4 proteins to examine virus egress. We found that production of infectious AcMNPV BV was substantially reduced by expression of DN VPS4 but not by WT VPS4. Together, these results indicate that a functional VPS4 is necessary for efficient AcMNPV BV entry into, and egress from, insect cells. PMID- 22072777 TI - Deltagamma1134.5 herpes simplex viruses encoding human cytomegalovirus IRS1 or TRS1 induce interferon regulatory factor 3 phosphorylation and an interferon stimulated gene response. AB - The chimeric herpes simplex viruses (HSV) are Deltagamma134.5 vectors encoding the human cytomegalovirus (HCMV) IRS1 or TRS1 genes. They are capable of late viral protein synthesis and are superior to Deltagamma134.5 HSVs in oncolytic activity. The interferon (IFN) response limits efficient HSV gene expression and replication. HCMV TRS1 and IRS1 restore one gamma134.5 gene function: evasion of IFN-inducible protein kinase R, allowing late viral protein synthesis. Here we show that, unlike wild-type HSV, the chimeric HSV do not restore another gamma134.5 function, the suppression of early IFN signaling mediated by IFN regulatory factor 3 (IRF3). PMID- 22072778 TI - Recent mumps outbreaks in vaccinated populations: no evidence of immune escape. AB - Recently, numerous large-scale mumps outbreaks have occurred in vaccinated populations. Clinical isolates sequenced from these outbreaks have invariably been of genotypes distinct from those of vaccine viruses, raising concern that certain mumps virus strains may escape vaccine-induced immunity. To investigate this concern, sera obtained from children 6 weeks after receipt of measles, mumps, and rubella (MMR) vaccine were tested for the ability to neutralize a carefully selected group of genetically diverse mumps virus strains. Although the geometric mean neutralizing antibody titer of the sera was lower against some virus strains than others, all viruses were readily neutralized, arguing against immune escape. PMID- 22072779 TI - A pH-sensitive heparin-binding sequence from Baculovirus gp64 protein is important for binding to mammalian cells but not to Sf9 insect cells. AB - Binding to heparan sulfate is essential for baculovirus transduction of mammalian cells. Our previous study shows that gp64, the major glycoprotein on the virus surface, binds to heparin in a pH-dependent way, with a stronger binding at pH 6.2 than at 7.4. Using fluorescently labeled peptides, we mapped the pH-dependent heparin-binding sequence of gp64 to a 22-amino-acid region between residues 271 and 292. Binding of this region to the cell surface was also pH dependent, and peptides containing this sequence could efficiently inhibit baculovirus transduction of mammalian cells at pH 6.2. When the heparin-binding peptide was immobilized onto the bead surface to mimic the high local concentration of gp64 on the virus surface, the peptide-coated magnetic beads could efficiently pull down cells expressing heparan sulfate but not cells pretreated with heparinase or cells not expressing heparan sulfate. Interestingly, although this heparin binding function is essential for baculovirus transduction of mammalian cells, it is dispensable for infection of Sf9 insect cells. Virus infectivity on Sf9 cells was not reduced by the presence of heparin or the identified heparin-binding peptide, even though the peptide could bind to Sf9 cell surface and be efficiently internalized. Thus, our data suggest that, depending on the availability of the target molecules on the cell surface, baculoviruses can use two different methods, electrostatic interaction with heparan sulfate and more specific receptor binding, for cell attachment. PMID- 22072780 TI - Complex dynamic development of poliovirus membranous replication complexes. AB - Replication of all positive-strand RNA viruses is intimately associated with membranes. Here we utilize electron tomography and other methods to investigate the remodeling of membranes in poliovirus-infected cells. We found that the viral replication structures previously described as "vesicles" are in fact convoluted, branching chambers with complex and dynamic morphology. They are likely to originate from cis-Golgi membranes and are represented during the early stages of infection by single-walled connecting and branching tubular compartments. These early viral organelles gradually transform into double-membrane structures by extension of membranous walls and/or collapsing of the luminal cavity of the single-membrane structures. As the double-membrane regions develop, they enclose cytoplasmic material. At this stage, a continuous membranous structure may have double- and single-walled membrane morphology at adjacent cross-sections. In the late stages of the replication cycle, the structures are represented mostly by double-membrane vesicles. Viral replication proteins, double-stranded RNA species, and actively replicating RNA are associated with both double- and single membrane structures. However, the exponential phase of viral RNA synthesis occurs when single-membrane formations are predominant in the cell. It has been shown previously that replication complexes of some other positive-strand RNA viruses form on membrane invaginations, which result from negative membrane curvature. Our data show that the remodeling of cellular membranes in poliovirus-infected cells produces structures with positive curvature of membranes. Thus, it is likely that there is a fundamental divergence in the requirements for the supporting cellular membrane-shaping machinery among different groups of positive strand RNA viruses. PMID- 22072781 TI - The toll-like receptor 3-mediated antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice. AB - RIG-I-like receptors and Toll-like receptors (TLRs) play important roles in the recognition of viral infections. However, how these molecules contribute to the defense against poliovirus (PV) infection remains unclear. We characterized the roles of these sensors in PV infection in transgenic mice expressing the PV receptor. We observed that alpha/beta interferon (IFN-alpha/beta) production in response to PV infection occurred in an MDA5-dependent but RIG-I-independent manner in primary cultured kidney cells in vitro. These results suggest that, similar to the RNA of other picornaviruses, PV RNA is recognized by MDA5. However, serum IFN-alpha levels, the viral load in nonneural tissues, and mortality rates did not differ significantly between MDA5-deficient mice and wild type mice. In contrast, we observed that serum IFN production was abrogated and that the viral load in nonneural tissues and mortality rates were both markedly higher in TIR domain-containing adaptor-inducing IFN-beta (TRIF)-deficient and TLR3-deficient mice than in wild-type mice. The mortality rate of MyD88-deficient mice was slightly higher than that of wild-type mice. These results suggest that multiple pathways are involved in the antiviral response in mice and that the TLR3-TRIF-mediated signaling pathway plays an essential role in the antiviral response against PV infection. PMID- 22072782 TI - Potent intratype neutralizing activity distinguishes human immunodeficiency virus type 2 (HIV-2) from HIV-1. AB - HIV-2 has a lower pathogenicity and transmission rate than HIV-1. Neutralizing antibodies could be contributing to these observations. Here we explored side by side the potency and breadth of intratype and intertype neutralizing activity (NAc) in plasma of 20 HIV-1-, 20 HIV-2-, and 11 dually HIV-1/2 (HIV-D) seropositive individuals from Guinea-Bissau, West Africa. Panels of primary isolates, five HIV-1 and five HIV-2 isolates, were tested in a plaque reduction assay using U87.CD4-CCR5 cells as targets. Intratype NAc in HIV-2 plasma was found to be considerably more potent and also broader than intratype NAc in HIV-1 plasma. This indicates that HIV-2-infected individuals display potent type specific neutralizing antibodies, whereas such strong type-specific antibodies are absent in HIV-1 infection. Furthermore, the potency of intratype NAc was positively associated with the viral load of HIV-1 but not HIV-2, suggesting that NAc in HIV-1 infection is more antigen stimulation dependent than in HIV-2 infection, where plasma viral loads typically are at least 10-fold lower than in HIV-1 infection. Intertype NAc of both HIV-1 and HIV-2 infections was, instead, of low potency. HIV-D subjects had NAc to HIV-2 with similar high potency as singly HIV-2-infected individuals, whereas neutralization of HIV-1 remained poor, indicating that the difference in NAc between HIV-1 and HIV-2 infections depends on the virus itself. We suggest that immunogenicity and/or antigenicity, meaning the neutralization phenotype, of HIV-2 is distinct from that of HIV-1 and that HIV-2 may display structures that favor triggering of potent neutralizing antibody responses. PMID- 22072783 TI - Epigenetic changes mediated by microRNA miR29 activate cyclooxygenase 2 and lambda-1 interferon production during viral infection. AB - Lambda-1 interferon (IFN-lambda1) and cyclooxygenase-2 (COX-2) were reported to play an important role in host antiviral defense. However, the mechanism by which IFN-lambda1 and COX2 are activated and modulated during viral infection remains unclear. In this study, we found that expression of both circulating IFN-lambda1 and COX2-derived prostaglandin E2 (PGE2) was coordinately elevated in a cohort of influenza patients compared to healthy individuals. Expression of IFN-lambda1 was blocked by a selective COX2 inhibitor during influenza A virus infection in A549 human lung epithelial cells but enhanced by overexpression of COX2, indicating that the production of IFN-lambda1 is COX2 dependent. COX2 was able to increase IFN-lambda1 expression by promoting NF-kappaB binding to the enhancer in the IFN lambda1 promoter. We found that epigenetic changes activate COX2 expression and PGE2 accumulation during viral infection. The expression of DNA methyltransferase 3a (DNMT3a) and DNMT3b, but not that of DNMT1, was downregulated following influenza A virus infection in both A549 cells and peripheral blood mononuclear cells (PBMCs). We showed that microRNA miR29 suppresses DNMT activity and thus induces expression of COX2 and PGE2. Furthermore, miR29 expression was elevated 50-fold in virally infected A549 cells and 10-fold in PBMCs from influenza patients, compared to expression after mock infection of A549 cells or in healthy individuals, respectively. Activation of the protein kinase A signaling pathway and phosphorylation of CREB1 also contributed to COX2 expression. Collectively, our work defines a novel proinflammatory cascade in the control of influenza A virus infection. PMID- 22072784 TI - Impact of vaccination on cytotoxic T lymphocyte immunodominance and cooperation against simian immunodeficiency virus replication in rhesus macaques. AB - Cytotoxic T lymphocyte (CTL) responses play a central role in viral suppression in human immunodeficiency virus (HIV) infections. Prophylactic vaccination resulting in effective CTL responses after viral exposure would contribute to HIV control. It is important to know how CTL memory induction by vaccination affects postexposure CTL responses. We previously showed vaccine-based control of a simian immunodeficiency virus (SIV) challenge in a group of Burmese rhesus macaques sharing a major histocompatibility complex class I haplotype. Gag(206 216) and Gag(241-249) epitope-specific CTL responses were responsible for this control. In the present study, we show the impact of individual epitope-specific CTL induction by prophylactic vaccination on postexposure CTL responses. In the acute phase after SIV challenge, dominant Gag(206-216)-specific CTL responses with delayed, naive-derived Gag(241-249)-specific CTL induction were observed in Gag(206-216) epitope-vaccinated animals with prophylactic induction of single Gag(206-216) epitope-specific CTL memory, and vice versa in Gag(241-249) epitope vaccinated animals with single Gag(241-249) epitope-specific CTL induction. Animals with Gag(206-216)-specific CTL induction by vaccination selected for a Gag(206-216)-specific CTL escape mutation by week 5 and showed significantly less decline of plasma viral loads from week 3 to week 5 than in Gag(241-249) epitope vaccinated animals without escape mutations. Our results present evidence indicating significant influence of prophylactic vaccination on postexposure CTL immunodominance and cooperation of vaccine antigen-specific and non-vaccine antigen-specific CTL responses, which affects virus control. These findings provide great insights into antigen design for CTL-inducing AIDS vaccines. PMID- 22072785 TI - Structural characterization of the hemagglutinin receptor specificity from the 2009 H1N1 influenza pandemic. AB - Influenza virus hemagglutinin (HA) is the viral envelope protein that mediates viral attachment to host cells and elicits membrane fusion. The HA receptor binding specificity is a key determinant for the host range and transmissibility of influenza viruses. In human pandemics of the 20th century, the HA normally has acquired specificity for human-like receptors before widespread infection. Crystal structures of the H1 HA from the 2009 human pandemic (A/California/04/2009 [CA04]) in complex with human and avian receptor analogs reveal conserved recognition of the terminal sialic acid of the glycan ligands. However, favorable interactions beyond the sialic acid are found only for alpha2 6-linked glycans and are mediated by Asp190 and Asp225, which hydrogen bond with Gal-2 and GlcNAc-3. For alpha2-3-linked glycan receptors, no specific interactions beyond the terminal sialic acid are observed. Our structural and glycan microarray analyses, in the context of other high-resolution HA structures with alpha2-6- and alpha2-3-linked glycans, now elucidate the structural basis of receptor-binding specificity for H1 HAs in human and avian viruses and provide a structural explanation for the preference for alpha2-6 siaylated glycan receptors for the 2009 pandemic swine flu virus. PMID- 22072787 TI - Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. AB - SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease. PMID- 22072788 TI - Recruitment of OCRL and Inpp5B to phagosomes by Rab5 and APPL1 depletes phosphoinositides and attenuates Akt signaling. AB - Sealing of phagosomes is accompanied by the disappearance of phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P(2)) from their cytoplasmic leaflet. Elimination of PtdIns(4,5)P(2), which is required for actin remodeling during phagosome formation, has been attributed to hydrolysis by phospholipase C and phosphorylation by phosphatidylinositol 3-kinase. We found that two inositol 5 phosphatases, OCRL and Inpp5B, become associated with nascent phagosomes. Both phosphatases, which are Rab5 effectors, associate with the adaptor protein APPL1, which is recruited to the phagosomes by active Rab5. Knockdown of APPL1 or inhibition of Rab5 impairs association of OCRL and Inpp5B with phagosomes and prolongs the presence of PtdIns(4,5)P(2) and actin on their membranes. Even though APPL1 can serve as an anchor for Akt, its depletion accentuated the activation of the kinase, likely by increasing the amount of PtdIns(4,5)P(2) available to generate phosphatidylinositol (3,4,5)-trisphosphate. Thus, inositol 5-phosphatases are important contributors to the phosphoinositide remodeling and signaling that are pivotal for phagocytosis. PMID- 22072786 TI - Human pathogens and the host cell SUMOylation system. AB - Since posttranslational modification (PTM) by the small ubiquitin-related modifiers (SUMOs) was discovered over a decade ago, a huge number of cellular proteins have been found to be reversibly modified, resulting in alteration of differential cellular pathways. Although the molecular consequences of SUMO attachment are difficult to predict, the underlying principle of SUMOylation is altering inter- and/or intramolecular interactions of the modified substrate, changing localization, stability, and/or activity. Unsurprisingly, many different pathogens have evolved to exploit the cellular SUMO modification system due to its functional flexibility and far-reaching functional downstream consequences. Although the extensive knowledge gained so far is impressive, a definitive conclusion about the role of SUMO modification during virus infection in general remains elusive and is still restricted to a few, yet promising concepts. Based on the available data, this review aims, first, to provide a detailed overview of the current state of knowledge and, second, to evaluate the currently known common principles/molecular mechanisms of how human pathogenic microbes, especially viruses and their regulatory proteins, exploit the host cell SUMO modification system. PMID- 22072790 TI - The kinase activity of human Rio1 is required for final steps of cytoplasmic maturation of 40S subunits. AB - RIO proteins form a conserved family of atypical protein kinases. Humans possess three distinct RIO kinases-hRio1, hRio2, and hRio3, of which only hRio2 has been characterized with respect to its role in ribosomal biogenesis. Here we show that both hRio1 and hRio3, like hRio2, are associated with precursors of 40S ribosomal subunits in human cells. Furthermore, we demonstrate that depletion of hRio1 by RNA interference affects the last step of 18S rRNA maturation and causes defects in the recycling of several trans-acting factors (hEnp1, hRio2, hLtv1, hDim2/PNO1, and hNob1) from pre-40S subunits in the cytoplasm. Although the effects of hRio1 and hRio2 depletion are similar, we show that the two kinases are not fully interchangeable. Moreover, rescue experiments with a kinase-dead mutant of hRio1 revealed that the kinase activity of hRio1 is essential for the recycling of the endonuclease hNob1 and its binding partner hDim2 from cytoplasmic pre-40S. Kinase-dead hRio1 is trapped on pre-40S particles containing hDim2 and hNob1 but devoid of hEnp1, hLtv1, and hRio2. These data reveal a role of hRio1 in the final stages of cytoplasmic pre-40S maturation. PMID- 22072789 TI - Yeast mRNA cap-binding protein Cbc1/Sto1 is necessary for the rapid reprogramming of translation after hyperosmotic shock. AB - In response to osmotic stress, global translation is inhibited, but the mRNAs encoding stress-protective proteins are selectively translated to allow cell survival. To date, the mechanisms and factors involved in the specific translation of osmostress-responsive genes in Saccharomyces cerevisiae are unknown. We find that the mRNA cap-binding protein Cbc1 is important for yeast survival under osmotic stress. Our results provide new evidence supporting a role of Cbc1 in translation initiation. Cbc1 associates with polysomes, while the deletion of the CBC1 gene causes hypersensitivity to the translation inhibitor cycloheximide and yields synthetic "sickness" in cells with limiting amounts of translation initiator factor eIF4E. In cbc1Delta mutants, translation drops sharply under osmotic stress, the subsequent reinitiation of translation is retarded, and "processing bodies" containing untranslating mRNAs remain for long periods. Furthermore, osmostress-responsive mRNAs are transcriptionally induced after osmotic stress in cbc1Delta cells, but their rapid association with polysomes is delayed. However, in cells containing a thermosensitive eIF4E allele, their inability to grow at 37oC is suppressed by hyperosmosis, and Cbc1 relocalizes from nucleus to cytoplasm. These data support a model in which eIF4E translation could be stress-sensitive, while Cbc1-mediated translation is necessary for the rapid translation of osmostress-protective proteins under osmotic stress. PMID- 22072791 TI - FAT10 is a proteasomal degradation signal that is itself regulated by ubiquitination. AB - FAT10 is a ubiquitin-like protein modifier that is induced in vertebrates following certain inflammatory stimuli. Its functions and the repertoire of its target substrates have remained elusive. In contrast to ubiquitin, its cellular abundance is tightly controlled by both transcriptional and posttranslational regulation, and it was reported to be rapidly degraded by the proteasome. Here we provide data to indicate that the degradation of FAT10 requires ubiquitination: degradation was inhibited in cells expressing a ubiquitin mutant that cannot be polymerized and in a mutant cell harboring a thermolabile ubiquitin-activating enzyme, E1. Of importance, FAT10 can serve as a degradation signal for otherwise stable proteins, and in this case, too, the targeting to the proteasome requires ubiquitination. Degradation of FAT10 is accelerated after induction of apoptosis, suggesting that it plays a role in prosurvival pathways. PMID- 22072792 TI - Three-dimensional structure of the radial spokes reveals heterogeneity and interactions with dyneins in Chlamydomonas flagella. AB - Radial spokes (RSs) play an essential role in the regulation of axonemal dynein activity and thus of ciliary and flagellar motility. However, few details are known about the complexes involved. Using cryo-electron tomography and subtomogram averaging, we visualized the three-dimensional structure of the radial spokes in Chlamydomonas flagella in unprecedented detail. Unlike many other species, Chlamydomonas has only two spokes per axonemal repeat, RS1 and RS2. Our data revealed previously uncharacterized features, including two-pronged spoke bases that facilitate docking to the doublet microtubules, and that inner dyneins connect directly to the spokes. Structures of wild type and the headless spoke mutant pf17 were compared to define the morphology and boundaries of the head, including a direct RS1-to-RS2 interaction. Although the overall structures of the spokes are very similar, we also observed some differences, corroborating recent findings about heterogeneity in the docking of RS1 and RS2. In place of a third radial spoke we found an uncharacterized, shorter electron density named "radial spoke 3 stand-in," which structurally bears no resemblance to RS1 and RS2 and is unaltered in the pf17 mutant. These findings demonstrate that radial spokes are heterogeneous in structure and may play functionally distinct roles in axoneme regulation. PMID- 22072793 TI - Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton. AB - The small GTPase Rab35 regulates endosomal membrane trafficking but also recruits effectors that modulate actin assembly and organization. Differentially expressed in normal and neoplastic cells (DENN)-domain proteins are a newly identified class of Rab guanine-nucleotide exchange factors (GEFs) that are grouped into eight families, each activating a common Rab. The members of one family, connecdenn 1-3/DENND1A-C, are all GEFs for Rab35. Why Rab35 requires multiple GEFs is unknown. We demonstrate that connecdenn 3 uses a unique C-terminal motif, a feature not found in connecdenn 1 or 2, to directly bind actin. This interaction couples Rab35 activation to the actin cytoskeleton, resulting in dramatic changes in cell shape, notably the formation of protrusive membrane extensions. These alterations are specific to Rab35 activated by connecdenn 3 and require both the actin-binding motif and N-terminal DENN domain, which harbors the GEF activity. It was previously demonstrated that activated Rab35 recruits the actin-bundling protein fascin to actin, but the relevant GEF for this activity was unknown. We demonstrate that connecdenn 3 and Rab35 colocalize with fascin and actin filaments, suggesting that connecdenn 3 is the relevant GEF. Thus, whereas connecdenn 1 and 2 activate Rab35 for endosomal trafficking, connecdenn 3 uniquely activates Rab35 for its role in actin regulation. PMID- 22072794 TI - Dependence of Chs2 ER export on dephosphorylation by cytoplasmic Cdc14 ensures that septum formation follows mitosis. AB - Cytokinesis, which leads to the physical separation of two dividing cells, is normally restrained until after nuclear division. In Saccharomyces cerevisiae, chitin synthase 2 (Chs2), which lays down the primary septum at the mother daughter neck, also ensures proper actomyosin ring constriction during cytokinesis. During the metaphase-to-anaphase transition, phosphorylation of Chs2 by the mitotic cyclin-dependent kinase (Cdk1) retains Chs2 at the endoplasmic reticulum (ER), thereby preventing its translocation to the neck. Upon Cdk1 inactivation at the end of mitosis, Chs2 is exported from the ER and targeted to the neck. The mechanism for triggering Chs2 ER export thus far is unknown. We show here that Chs2 ER export requires the direct reversal of the inhibitory Cdk1 phosphorylation sites by Cdc14 phosphatase, the ultimate effector of the mitotic exit network (MEN). We further show that only Cdc14 liberated by the MEN after completion of chromosome segregation, and not Cdc14 released in early anaphase by the Cdc fourteen early anaphase release pathway, triggers Chs2 ER exit. Presumably, the reduced Cdk1 activity in late mitosis further favors dephosphorylation of Chs2 by Cdc14. Thus, by requiring declining Cdk1 activity and Cdc14 nuclear release for Chs2 ER export, cells ensure that septum formation is contingent upon chromosome separation and exit from mitosis. PMID- 22072795 TI - miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies. AB - microRNAs (miRNAs) and RNA-binding proteins (RBPs) jointly regulate gene expression at the posttranscriptional level and are involved in many aspects of cellular functions. The RBP CUG-binding protein 1 (CUGBP1) destabilizes and represses the translation of several target mRNAs, but the exact mechanism that regulates CUGBP1 abundance remains elusive. In this paper, we show that miR-503, computationally predicted to associate with three sites of the CUGBP1 mRNA, represses CUGBP1 expression. Overexpression of an miR-503 precursor (pre-miR-503) reduced the de novo synthesis of CUGBP1 protein, whereas inhibiting miR-503 by using an antisense RNA (antagomir) enhanced CUGBP1 biosynthesis and elevated its abundance; neither intervention changed total CUGBP1 mRNA levels. Studies using heterologous reporter constructs revealed a greater repressive effect of miR-503 through the CUGBP1 coding region sites than through the single CUGBP1 3' untranslated region target site. CUGBP1 mRNA levels in processing bodies (P bodies) increased in cells transfected with pre-miR-503, while silencing P-body resident proteins Ago2, RCK, or LSm4 decreased miR-503-mediated repression of CUGBP1 expression. Decreasing the levels of cellular polyamines reduced endogenous miR-503 levels and promoted CUGBP1 expression, an effect that was prevented by ectopic miR-503 overexpression. Repression of CUGBP1 by miR-503 in turn altered the expression of CUGBP1 target mRNAs and thus increased the sensitivity of intestinal epithelial cells to apoptosis. These findings identify miR-503 as both a novel regulator of CUGBP1 expression and a modulator of intestinal epithelial homoeostasis. PMID- 22072798 TI - The patient impact factor. PMID- 22072796 TI - UHRF1 phosphorylation by cyclin A2/cyclin-dependent kinase 2 is required for zebrafish embryogenesis. AB - Ubiquitin-like, containing PHD and RING finger domains 1 (uhrf1) is regulated at the transcriptional level during the cell cycle and in developing zebrafish embryos. We identify phosphorylation as a novel means of regulating UHRF1 and demonstrate that Uhrf1 phosphorylation is required for gastrulation in zebrafish. Human UHRF1 contains a conserved cyclin-dependent kinase 2 (CDK2) phosphorylation site at Ser-661 that is phosphorylated in vitro by CDK2 partnered with cyclin A2 (CCNA2), but not cyclin E. An antibody specific for phospho-Ser-661 recognizes UHRF1 in both mammalian cancer cells and in nontransformed zebrafish cells, but not in zebrafish bearing a mutation in ccna2. Depleting Uhrf1 from zebrafish embryos by morpholino injection causes arrest before gastrulation and early embryonic death. This phenotype is rescued by wild-type UHRF1, but not by UHRF1 in which the phospho-acceptor site is mutated, demonstrating that UHRF1 phosphorylation is essential for embryogenesis. UHRF1 was detected in the nucleus and cytoplasm, whereas nonphosphorylatable UHRF1 is unable to localize to the cytoplasm, suggesting the importance of localization in UHRF1 function. Together, these data point to an essential role for UHRF1 phosphorylation by CDK/CCNA2 during early vertebrate development. PMID- 22072799 TI - Shining the light on aurora-a kinase as a drug target in pancreatic cancer. PMID- 22072800 TI - First report of functional Chk1 siRNA studies applied to drug discovery. PMID- 22072801 TI - The discovery and development of SU14813, a next-generation multitargeted tyrosine kinase inhibitor for the treatment of human malignancies. PMID- 22072802 TI - PI3K inhibitors for cancer treatment: five years of preclinical and clinical research after BEZ235. PMID- 22072803 TI - Discovering and developing PI3 kinase inhibitors for cancer: rapid progress through academic-biotech-pharma interactions. PMID- 22072804 TI - The discovery of lapatinib (GW572016). PMID- 22072805 TI - Methylation profiling of lung cancer: a decade of progress. PMID- 22072806 TI - MicroRNAs in cancer pharmacology and therapeutics: exploiting a natural synergy between '-omic' and hypothesis-driven research. PMID- 22072807 TI - Development of the first generation c-met kinase inhibitors: beginning of a path to a new treatment for cancer. PMID- 22072808 TI - Proof of principle for crizotinib in anaplastic lymphoma kinase-positive malignancies was achieved in ALK-positive nonclinical models. PMID- 22072809 TI - Lapatinib: functional genomics study leads to insights into mechanism of action. PMID- 22072810 TI - Bench to bedside and back again: personalizing treatment for patients with GIST. PMID- 22072811 TI - The importance of PK/PD data-key biological answers needed to evaluate the success of potential cancer therapeutics. PMID- 22072812 TI - Bortezomib: understanding the mechanism of action. PMID- 22072813 TI - Starting with the ABCs: Akt in breast cancer. PMID- 22072814 TI - Cell line models identify different sensitivity of mutant forms of c-KIT to kinase inhibitory drugs and predict the response of patients to therapy. PMID- 22072815 TI - Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma. AB - Novel agents, including the proteasome inhibitor bortezomib, have significantly improved the response and survival of patients with multiple myeloma over the last decade. Despite these advances, many patients relapse or do not benefit from the currently available therapies; thus, multiple myeloma remains an incurable disease. Deacetylase inhibitors (DACi), including panobinostat and vorinostat, have recently emerged as novel agents being evaluated in the treatment of multiple myeloma. Deacetylases are a group of enzymes with effects on various intracellular proteins, including histones, transcription factors, and molecular chaperones. Although DACi inhibit cell growth and induce apoptosis in multiple myeloma cells as a single agent, synergistic activity has been observed when they were used in combination with bortezomib. The mechanistic basis of synergy is multifactorial and includes disruption of protein degradation and inhibition of the interaction of multiple myeloma cells with the tumor microenvironment. This review summarizes recent advancements in the understanding of the mechanism of action of proteasome inhibitors and DACi in multiple myeloma and examines the biological basis of their synergistic effects. Data from the studies summarized here have been used as the rationale for the implementation of phase II and III clinical trials of DACi, alone and combined with bortezomib, in relapsed and refractory multiple myeloma. PMID- 22072816 TI - Microarray analysis of the primate luteal transcriptome during chorionic gonadotrophin administration simulating early pregnancy. AB - To explore chorionic gonadotrophin (CG)-regulated gene expression in the primate corpus luteum (CL), adult female rhesus macaques were treated in a model of simulated early pregnancy (SEP). Total RNA was isolated from individual CL after specific intervals of exposure (1, 3, 6 and 9 days) to recombinant hCG in vivo and hybridized to AffymetrixTM GeneChip Rhesus Macaque Genome Arrays. The mRNA levels of 1192 transcripts changed >=2-fold [one-way ANOVA, false discovery rate (FDR) correction; P< 0.05] during SEP when compared with Day 10 untreated controls. Real-time PCR validation indicated that 15 of 17 genes matched in expression pattern between PCR and microarray. Protein levels of three genes identified as CG-sensitive, CYP19A1 (aromatase), PGRMC1 (progestin-binding protein) and STAR (steroidogenic acute regulatory protein) were quantified by western blot analysis. To further analyze global changes in gene expression induced by CG exposure, luteal gene expression was compared between SEP (rescued) and regressing CL, utilizing previously banked GeneChip data from the luteal phase of the menstrual cycle. Expression patterns and mRNA levels were analyzed between time-matched intervals. Transcripts for 7677 mRNAs differed in expression patterns >=2-fold (one-way ANOVA, FDR correction; P< 0.05) between the hCG exposed (SEP) CL and regressing CL. Regressed CL (at menses) were most unlike all other CL. Pathway analysis of significantly affected transcripts was performed; the pathway most impacted by CG exposure was steroid biosynthesis. Further comparisons of the genome-wide changes in luteal gene expression during CG rescue and luteolysis in the natural menstrual cycle should identify additional key regulatory pathways promoting primate fertility. PMID- 22072817 TI - The novel antipsychotic drug lurasidone enhances N-methyl-D-aspartate receptor mediated synaptic responses. AB - N-Methyl-D-aspartate (NMDA) receptor (NMDAR) hypofunction has been postulated to contribute to the cognitive deficit of schizophrenia. In this study, we examined the effect of lurasidone (Latuda; Dainippon Sumitomo Pharma Co. Ltd., Tokyo, Japan), a newly approved atypical antipsychotic drug (APD), on NMDAR synaptic function in rat frontal cortical pyramidal neurons. In vivo administration of lurasidone produced a significant and selective enhancement of NMDAR-mediated synaptic responses and surface expression of NR2A and NR2B subunits. Lurasidone has high affinity for serotonin 5-HT(1A), 5-HT(2A), and 5-HT(7) receptors and dopamine D(2) receptors. In vivo administration of the 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2 -(2-(4-methyl-1 piperidinyl)ethyl)pyrrolidine (SB-269970) mimicked the enhancing effect of lurasidone on NMDAR responses, whereas the D(2) receptor antagonist haloperidol failed to do so. Previous studies have found that short-term administration of lurasidone reverses the cognitive impairment induced by subchronic administration of phencyclidine (PCP), an NMDAR noncompetitive antagonist. In this study, we found that lurasidone, as well as the prototypical atypical APD clozapine, restored NMDAR-mediated synaptic responses to normal levels in the PCP model of schizophrenia. These results suggest that NMDAR is the potential key molecular target of lurasidone, possibility via antagonizing 5-HT(7) receptors, which is consistent with evidence that 5-HT(7) receptor antagonism contributes to cognitive enhancement by atypical APDs in patients with schizophrenia. PMID- 22072818 TI - Allosteric interactions between delta and kappa opioid receptors in peripheral sensory neurons. AB - The peripheral delta opioid receptor (DOR) is an attractive target for analgesic drug development. There is evidence that DOR can form heteromers with the kappa opioid receptor (KOR). As drug targets, heteromeric receptors offer an additional level of selectivity and, because of allosteric interactions between protomers, functionality. Here we report that selective KOR antagonists differentially altered the potency and/or efficacy of DOR agonists in primary cultures of adult rat peripheral sensory neurons and in a rat behavioral model of thermal allodynia. In vitro, the KOR antagonist nor-binaltorphimine (nor-BNI) enhanced the potency of [D-Pen(2,5)]-enkephalin (DPDPE), decreased the potency of [D Ala(2),D-Leu(5)]-enkephalin (DADLE), and decreased the potency and efficacy of 4 [(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazin-1-yl](3-methoxyphenyl)methyl]-N,N diethylbenzamide (SNC80) to inhibit prostaglandin E(2) (PGE(2))-stimulated adenylyl cyclase activity. In vivo, nor-BNI enhanced the effect of DPDPE and decreased the effect of SNC80 to inhibit PGE(2)-stimulated thermal allodynia. In contrast to nor-BNI, the KOR antagonist 5'-guanidinonaltrindole (5'-GNTI) reduced the response of DPDPE both in cultured neurons and in vivo. Evidence for DOR-KOR heteromers in peripheral sensory neurons included coimmunoprecipitation of DOR with KOR, a DOR-KOR heteromer selective antibody augmented the antinociceptive effect of DPDPE in vivo, and the DOR-KOR heteromer agonist 6'-GNTI inhibited adenylyl cyclase activity in vitro as well as PGE(2)-stimulated thermal allodynia in vivo. Taken together, these data suggest that DOR-KOR heteromers exist in rat primary sensory neurons and that KOR antagonists can act as modulators of DOR agonist responses most likely through allosteric interactions between the protomers of the DOR-KOR heteromer. PMID- 22072819 TI - Development and clinical evaluation of a rapid serodiagnostic test for toxoplasmosis of cats using recombinant SAG1 antigen. AB - Rapid serodiagnostic methods for Toxoplasma gondii infection in cats are urgently needed for effective control of transmission routes toward human infections. In this work, 4 recombinant T. gondii antigens (SAG1, SAG2, GRA3, and GRA6) were produced and tested for the development of rapid diagnostic test (RDT). The proteins were expressed in Escherichia coli, affinity-purified, and applied onto the nitrocellulose membrane of the test strip. The recombinant SAG1 (rSAG1) showed the strongest antigenic activity and highest specificity among them. We also performed clinical evaluation of the rSAG1-loaded RDT in 182 cat sera (55 household and 127 stray cats). The kit showed 0.88 of kappa value comparing with a commercialized ELISA kit, which indicated a significant correlation between rSAG1-loaded RDT and the ELISA kit. The overall sensitivity and specificity of the RDT were 100% (23/23) and 99.4% (158/159), respectively. The rSAG1-loaded RDT is rapid, easy to use, and highly accurate. Thus, it would be a suitable diagnostic tool for rapid detection of antibodies in T. gondii-infected cats under field conditions. PMID- 22072820 TI - Changing patterns of acute phase proteins and inflammatory mediators in experimental caprine coccidiosis. AB - This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1*10(3) and1*10(5) sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF alpha, and IFN-gamma were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 ug/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-alpha and IFN gamma with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non specific diagnostic indicators in caprine coccidiosis. PMID- 22072821 TI - Expressed sequence tag analysis of the erythrocytic stage of Plasmodium berghei. AB - Rodent malaria parasites, such as Plasmodium berghei, are practical and useful model organisms for human malaria research because of their analogies to the human malaria in terms of structure, physiology, and life cycle. Exploiting the available genetic sequence information, we constructed a cDNA library from the erythrocytic stages of P. berghei and analyzed the expressed sequence tag (EST). A total of 10,040 ESTs were generated and assembled into 2,462 clusters. These EST clusters were compared against public protein databases and 48 putative new transcripts, most of which were hypothetical proteins with unknown function, were identified. Genes encoding ribosomal or membrane proteins and purine nucleotide phosphorylases were highly abundant clusters in P. berghei. Protein domain analyses and the Gene Ontology functional categorization revealed translation/protein folding, metabolism, protein degradation, and multiple family of variant antigens to be mainly prevalent. The presently-collected ESTs and its bioinformatic analysis will be useful resources to identify for drug target and vaccine candidates and validate gene predictions of P. berghei. PMID- 22072822 TI - Non-specific defensive factors of the Pacific oyster Crassostrea gigas against infection with Marteilioides chungmuensis: a flow-cytometric study. AB - In order to assess changes in the activity of immunecompetency present in Crassostrea gigas infected with Marteilioides chungmuensis (Protozoa), the total hemocyte counts (THC), hemocyte populations, hemocyte viability, and phagocytosis rate were measured in oysters using flow cytometry. THC were increased significantly in oysters infected with M. chungmuensis relative to the healthy appearing oysters (HAO) (P<0.05). Among the total hemocyte composition, granulocyte levels were significantly increased in infected oysters as compared with HAO (P<0.05). In addition, the hyalinocyte was reduced significantly (P<0.05). The hemocyte viability did not differ between infected oysters and HAO. However, the phagocytosis rate was significantly higher in infected oysters relative to HAO (P<0.05). The measurement of alterations in the activity of immunecompetency in oysters, which was conducted via flow cytometry in this study, might be a useful biomarker of the defense system for evaluating the effects of ovarian parasites of C. gigas. PMID- 22072823 TI - Protease-activated receptor 2 is involved in Th2 responses against Trichinella spiralis infection. AB - In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection. PMID- 22072824 TI - Parasitic helminth cystatin inhibits DSS-induced intestinal inflammation via IL 10(+)F4/80(+) macrophage recruitment. AB - Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-alpha in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10(+)F4/80(+) macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages. PMID- 22072825 TI - In vitro effects of some herbs used in Egyptian traditional medicine on viability of protoscolices of hydatid cysts. AB - The present work evaluated the effects of alcoholic extracts of salvia (Salvia officinalis), thyme (Thymus vulgaris), and 2 pure compounds (thymol and menthol) on the viability of Echinococcus granulosus protoscolices in vitro. Four different concentrations of each extract (2,500, 1,500, 1,000, and 500 ug/ml) and 3 different concentrations each of thymol and menthol (50, 10, and 1 ug/ml) were used. Concentration of 2,500 ug/ml of both extracts showed a significant protoscolicidal activity on the 6th day. Complete loss of viability of protoscolices occurred with 500 ug/ml concentration of both extracts at day 6 and day 7 post-treatment (PT), respectively. Pure compounds, i.e., menthol and thymol, showed potent effects with 50 ug/ml concentration at day 2 and day 5 PT, respectively. These effects were compared with those of albendazole sulfoxide (800 ug/ml), a commonly used treatment drug for hydatidosis. Krebs-Ringer solution and the hydatid cystic fluid at a ratio of 4:1 was a good preservative solution which kept the protoscolices viable for 15 days. PMID- 22072826 TI - Two cases of human thelaziasis and brief review of Korean cases. AB - The present study was performed to describe 2 cases of human thelaziasis (HT) which occurred in Gyeongsangnam- do and to briefly review the previously reported Korean cases. A 58-year old woman, residing in Hadong-gun, Gyeongsangnam-do, came to Gyeongsang National University Hospital (GNUH) complaining of foreign body sensation and itching of the right eye in March 2000. Total 6 adult nematodes of Thelazia callipaeda (2 males and 4 females) were detected in her right eye. A 80 year old man, residing in Jinju-si, Gyeongsangnam-do, came to GNUH complaining of foreign body sensation, itching, and pain of the right eye in December 2007. A total of 5 worms (4 females and 1 degenerated) were removed from his right eye. We analyzed characteristics of the total 39 Korean HT cases reported to date, including the present 2 cases. Most of the cases (71.8%) occurred in Seoul and Gyeonggi-do before 2000, and 21 cases (53.8%) were males and 18 (46.2%) were females. The prevalence was higher in younger ages below 30 years (48.7%) than 31 60 years (41.0%) and over 61 years (10.3%). The seasonal prevalence showed a higher incidence in autumn (43.6%) than in other seasons. Most of the cases (94.9%) were conjunctival sac infections and only 2 (5.1%) were intraocular cases. The present 2 HT cases are the first reported cases in Gyeongsangnam-do. Some characteristics of Korean HT cases were analyzed. PMID- 22072827 TI - Hypersensitive reaction to praziquantel in a clonorchiasis patient. AB - Praziquantel is the drug of choice for clonorchiasis. Since clonorchiasis is endemic in most river basins, praziquantel has been widely used for 30 years in Korea. A 54-year-old Korean woman suffered from hypersensitive reactions, such as nausea, dyspnea, rash, and urticaria after taking the first dose of praziquantel to treat clonorchiasis. She ingested one dose again and the same symptoms appeared, and she was treated at a clinic with anti-histamines. She tried one more dose with anti-histamines but found the same symptoms. Later, she was found to pass eggs of Clonorchis sinensis and medicated with flubendazole. The hypersensitive reaction to praziquantel is rare but occurs. This is the 5th case report in the world. PMID- 22072828 TI - Cystic echinococcosis of the pelvic bone with recurrences: a case report. AB - Hydatid cysts commonly affect the liver and the lung. However, they rarely involve bones with vertebral column. We hereby report a case of a female patient with cystic echinococcosis of the hip bone and ilium. She presented with a long history of frequent recurrences highlighting the dismal prognosis at this rare site. Resection of the hydatid cyst from the sacroiliac region was done with allograft and autograft (rib graft) with lumbosacroiliac fixation. Follow-up of the patient at 6 months showed no detectable abnormality on radiology and the patient was doing well. PMID- 22072829 TI - PCR diagnosis of Entamoeba histolytica cysts in stool samples. AB - Amebiasis is a protozoan disease caused by Entamoeba histolytica and a potential health threat in areas where sanitation and hygiene are inappropriate. Highly sensitive PCR methods for detection of E. histolytica in clinical and environmental samples are extremely useful to control amebiasis and to promote public health. The present study compared several primer sets for small subunit (SSU) rDNA and histone genes of E. histolytica cysts. A 246 bp of the SSU rDNA gene of pure cysts contained in phosphate-buffered saline (PBS) and in stool samples was successfully amplified by nested PCR, using the 1,147-246 bp primer set, of the primary PCR products which were pre-amplified using the 1,147 bp primer as the template. The detection limit of the nested PCR using the 1,147-246 primer set was 10 cysts in both groups (PBS and stool samples). The PCR to detect histone gene showed negative results. We propose that the nested PCR technique to detect SSU rDNA can be used as a highly sensitive genetic method to detect E. histolytica cysts in stool samples. PMID- 22072830 TI - Naegleria fowleri lysate induces strong cytopathic effects and pro-inflammatory cytokine release in rat microglial cells. AB - Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A (51)Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-alpha, IL-6, and IL 1beta, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response. PMID- 22072831 TI - NF-kappaB and CREB are involved in IL-8 production of human neutrophils induced by Trichomonas vaginalis-derived secretory products. AB - Trichomonas vaginalis is a flagellated lumen-dwelling extracellular protozoan parasite that causes human trichomoniasis via sexual intercourse. Human neutrophils play a crucial role in acute tissue inflammatory responses in T. vaginalis infection. In this study, we investigated the signaling mechanism of neutrophil responses when stimulated with T. vaginalis-derived secretory products (TvSP), which were collected from 1*10(7) live trichomonads. Incubation of human neutrophils isolated from peripheral blood with TvSP induced up-regulation of IL 8 protein secretion. In addition, stimulation with TvSP induced phosphorylation of NF-kappaB and CREB in neutrophils. Moreover, TvSP-induced IL-8 production was also significantly inhibited by pretreatment of neutrophils with ikappaB inhibitor or CREB inhibitor. These results suggest that transcription factors NF kappaB and CREB are involved in IL-8 production in human neutrophils induced by stimulation with T. vaginalis infection. PMID- 22072832 TI - Lactobacillus acidophilus contributes to a healthy environment for vaginal epithelial cells. AB - Lactobacillus species in the female genital tract are thought to act as a barrier to infection. Several studies have demonstrated that lactobacilli can adhere to vaginal epithelial cells. However, little is known about how the adherence of lactobacilli to vaginal epithelial cells affects the acidity, cell viability, or proliferation of the lactobacilli themselves or those of vaginal epithelial cells. Lactobacillus acidophilus was co-cultured with immortalized human vaginal epithelial cells (MS74 cell line), and the growth of L. acidophilus and the acidity of the culture medium were measured. MS74 cell density and viability were also assessed by counting cell numbers and observing the cell attachment state. L. acidophilus showed exponential growth for the first 6 hr until 9 hr, and the pH was maintained close to 4.0-5.0 at 24 hr after culture, consistent with previous studies. The growth curve of L. acidophilus or the pH values were relatively unaffected by co-culture with MS74 cells, confirming that L. acidophilus maintains a low pH in the presence of MS74 cells. This co-culture model could therefore potentially be used to mimic vaginal conditions for future in vitro studies. On the other hand, MS74 cells co-cultured with L. acidophilus more firmly attached to the culture plate, and a higher number of cells were present compared to cells cultured in the absence of L. acidophilus. These results indicate that L. acidophilus increases MS74 cell proliferation and viability, suggesting that lactobacilli may contribute to the healthy environment for vaginal epithelial cells. PMID- 22072833 TI - Effects of simple and disposable chicken cages for experimental Eimeria infections. AB - During experimental Eimeria infections in chickens, facilities are often contaminated by fecal oocysts known to be highly resistant to both chemical and enzymatic treatments. Thus, studies using experimental Eimeria infections have been limited due to the difficulty of complete elimination of residual oocysts from both cages and facilities. To overcome this limitation, simple, inexpensive, and disposable cages were constructed from cardboard boxes and tested during experimental Eimeria maxima infections. The cages were used in animal rooms with only a 1.7% evidence of coccidia contamination between adjacent cages. No significant differences in fecal oocyst output and body weight gain were noted between animals housed in disposable cages and animals housed in wire control cages. This cage design is a useful means for preventing oocyst contamination during experimental conditions, suggesting that this disposable cage design could be used for other avian infectious disease studies. PMID- 22072834 TI - Resistance to Toxoplasma gondii infection in mice treated with silk protein by enhanced immune responses. AB - This study investigated whether elevated host immune capacity can inhibit T. gondii infection. For this purpose, we used silk protein extracted from Bombyx mori cocoons as a natural supplement to augment immune capacity. After silk protein administration to BALB/c mice for 6 weeks, ratios of T lymphocytes (CD4(+) and CD8(+) T-cells) and splenocyte proliferative capacities in response to Con A or T. gondii lysate antigen (TLA) were increased. Of various cytokines, which regulate immune systems, Th1 cytokines, such as IFN-gamma, IL-2, and IL-12, were obviously increased in splenocyte primary cell cultures. Furthermore, the survival of T. gondii (RH strain)-infected mice increased from 2 days to 5 or more days. In a state of immunosuppression induced by methylprednisolone acetate, silk protein-administered mice were resistant to reduction in T-lymphocyte (CD4(+) and CD8(+) T-cells) numbers and the splenocyte proliferative capacity induced by Con A or TLA with a statistical significance. Taken together, our results suggest that silk protein augments immune capacity in mice and the increased cellular immunity by silk protein administration increases host protection against acute T. gondii infection. PMID- 22072835 TI - Maintained seroprevalence of toxoplasmosis among the residents of Jeju island, Korea. AB - Seroepidemiological status of toxoplasmosis among the residents of Jeju island was surveyed and evaluated by ELISA with crude extract of Toxoplasma gondii. The sera of 2,348 residents (male 1,157 and female 1,191) were collected and checked for the IgG antibody titers, which showed 13.2% positive rate (309 sera). The positive rates were increasing gradually according to the age from 4.3% in teenage to 20.6% in seventies. The positive rates were significantly different between the sex by 16.2% for male and 10.2% for female (P<0.05). This positive rate of toxoplasmosis in Jeju island residents is regarded relatively higher than any other regions of Korea. And the high positive rate may be maintained continuously among Jeju island residents without any clear reasons until now but due to some parts peculiar socio-cultural tradition of Jeju island. Therefore, it is necessary to study further the epidemiology of toxoplasmosis of Jeju island. PMID- 22072836 TI - Mosquito species composition and Plasmodium vivax infection rates on Baengnyeong do (island), Republic of Korea. AB - Vivax malaria is a significant military and civilian health threat in the north of the Republic of Korea (ROK). The island of Baengnyeong-do is the westernmost point of the ROK and is located close to the southwestern coast of the Democratic People's Republic of Korea (DPRK). Mosquitoes were collected using a black light trap on Baengnyeong-do, and Anopheles spp. were assayed by PCR, to identify the species, and screened for sporozoites of Plasmodium vivax. Of a subsample of 257 mosquitoes, Anopheles lesteri was the most frequently collected (49.8%), followed by Anopheles sinensis (22.6%), Anopheles pullus (18.7%), Anopheles kleini (7.8%), and Anopheles belenrae (1.2%). The overall sporozoite rate was 3.1%, with the highest rates observed in An. kleini (15.0%), An. sinensis (5.2%), and An. lesteri (1.6%). No sporozoite positive An. pullus or An. belenrae were observed. The results extend our knowledge of the distribution and potential role in malaria transmission of An. kleini, An. lesteri, and An. sinensis, for an area previously considered to be at a low risk for contracting vivax malaria. PMID- 22072837 TI - The Jeju weasel, Mustela sibilica quelpartis, a new definitive host for Gnathostoma nipponicum Yamaguti, 1941. AB - Adult gnathostomes were discovered in the stomach of the Jeju weasel, Mustela sibilica quelpartis, road-killed in Jeju-do (Province). Their morphological characters were examined to identify the species. Total 50 gnathostome adults were collected from 6 out of 10 weasels examined. In infected weasels, 4-6 worms were grouped and embedded in each granulomatous gastric tumor, except 1 weasel. Male worms were 25.0*1.4 mm in average size, and had a tail with pedunculate papillae, a spicule, and minute tegumental spines. Females were 40.0*2.5 mm in average size, and had a tail without tegumental spines. Pointed and posteriorly curved hooklets were arranged in 8-10 rows on the head bulb. Tegumental spines were distributed from behind the head bulb to the middle portion of the body. The spines were different in size and shape by the distribution level of the body surface. Fertilized eggs were 65.5*38.9 um in average size, and had a mucoid plug at 1 pole. These gnathostomes from Jeju weasels were identified as Gnathostoma nipponicum Yamaguti, 1941. By the present study, it was confirmed for the first time that G. nipponicum is distributed in Jeju-do, the Republic of Korea, and the Jeju weasel, M. sibilica quelpartis, plays a crucial role for its definitive host. PMID- 22072838 TI - Enterobius vermicularis eggs discovered in coprolites from a medieval Korean mummy. AB - While the presence of pinworm eggs in archaeological samples has been reported by many researchers in the New World, those have been detected very scarcely in the Old World, especially in East Asian countries. In fact, many parasite species were recovered from the archeological remains in Korea, eggs of Enterobius vermicularis had not been found. Recently, a female mummy buried in the 17th century was discovered in the Joseon tomb from Dangjin-gun, Chungcheongnam-do, Korea. After rehydration process for 12 days, investigations were carried on the luminal surface of the colon. From them, 3 eggs of E. vermicularis were recovered. They were elliptical, transparent with a thin egg shell, 50.3+/-5.2 um (length) and 28.2+/-3.9 um (width) in size. This is the first discovery of E. vermicularis eggs in East Asia. PMID- 22072839 TI - Discovery of taeniid eggs from a 17th century tomb in Korea. AB - Even though Taenia spp. eggs are occasionally discovered from archeological remains around the world, these eggs have never been discovered in ancient samples from Korea. When we attempted to re-examine the archeological samples maintained in our collection, the eggs of Taenia spp., 5 in total number, were recovered from a tomb of Gongju-si. The eggs had radially striated embryophore, and 37.5-40.0 um*37.5 um in size. This is the first report on taeniid eggs from ancient samples of Korea, and it is suggested that intensive examination of voluminous archeological samples should be needed for identification of Taenia spp. PMID- 22072840 TI - Ticks collected from selected mammalian hosts surveyed in the Republic of Korea during 2008-2009. AB - A tick survey was conducted to determine the relative abundance and distribution of ticks associated with selected mammals in the Republic of Korea (ROK) during 2008-2009. A total of 918 ticks were collected from 76 mammals (6 families, 9 species) captured at 6 provinces and 3 Metropolitan Cities in ROK. Haemaphysalis longicornis (54.4%) was the most frequently collected tick, followed by Haemaphysalis flava (28.5%), Ixodes nipponensis (7.6%), Ixodes pomerantzevi (4.8%), Ixodes persulcatus (4.6%), and Haemaphysalis japonica (0.1%). Adults (57.0%) and nymphs (28.7%) of Ixodes and Haemaphysalis spp. were collected most frequently from medium or large mammals in this survey, while few larvae (14.3%) were collected. Hydropotes inermis was the most frequently captured mammal (52.6%), with a 16.4 tick index and 5 of 6 species of ticks collected during this survey. H. longicornis (69.7%) was the predominant tick collected from H. inermis, followed by H. flava (22.2%), I. persulcatus (6.1%), I. nipponensis (1.8%), and H. japonica (0.2%). PMID- 22072841 TI - Predicting overt and covert antisocial behaviors: parents, peers, and homelessness. AB - Parental deviance, parental monitoring, and deviant peers were examined as predictors of overt and covert antisocial behaviors. Homeless (N=231) and housed (N=143) adolescents were assessed in adolescence and again in early adulthood. Homelessness predicted both types of antisocial behaviors, and effects persisted in young adulthood. Parental deviance predicted only overt antisocial behaviors in adolescence, and was fully mediated by parental monitoring. Parental monitoring predicted both types of antisocial behaviors in adolescence, and was partially mediated by peer deviance. Parenting and peer influences did not consistently predict antisocial behaviors in adulthood. PMID- 22072842 TI - Engagement in Adulthood: Perceptions and Participation in Daily Activities. AB - The present research explores how older adults experience daily activities through an application of the Day Reconstruction Method (Kahneman, Kreuger, Schakade, Schwartz, & Stone, 2004). Over the course of the day, individuals (N = 192, M = 72 years) spent an average of 14.50 hours engaged in a variety of activities. Individual differences in activity patterns could be partly explained by age and educational attainment. The oldest individuals (81-92 years) perceived lower levels of competence when engaging in daily activities. Regardless of age, however, individuals with greater educational attainment allocated more time and felt more intellectually challenged in their daily experiences. PMID- 22072843 TI - Challenges to Aging in Place: Understanding Home Maintenance Difficulties. AB - Age-related declines in capabilities may compromise older adults' ability to maintain their homes thus threatening successful aging in place. Structured interviews were conducted with forty-four independently living older adults (M(age) = 76.1, SD = 4.7) to discuss difficult home maintenance tasks and how they managed those tasks. Solutions to managing difficulties were categorized as person-related or environment-related. The majority (85%) of responses were person-related solutions. An understanding of the specific challenges that older adults face in maintaining their homes can guide redesign efforts and interventions to effectively support older adults' desire to age in place. PMID- 22072844 TI - Posttraumatic Stress and Alcohol Use Motives: A Test of the Incremental and Mediating Role of Distress Tolerance. AB - This investigation first examined the incremental validity of distress tolerance in terms of alcohol use coping motives within a trauma-exposed community sample of adults, beyond the variance contributed by posttraumatic stress symptom severity, difficulties in emotion regulation, alcohol consumption, and other (noncriterion) alcohol use motives. Secondly, the potential mediating role of distress tolerance in the association between posttraumatic stress symptom severity and alcohol use coping motives was tested. Participants were 83 community-recruited individuals (63.8% women; M(age) = 22.98, SD = 9.24) who endorsed exposure to at least one traumatic life event and past-month alcohol use. Participants were assessed using structured diagnostic interviews and a series of self-report inventories. Results were consistent with hypotheses, because distress tolerance was significantly and incrementally associated with alcohol use coping motives; and distress tolerance at least partially mediated the association between posttraumatic stress and alcohol use coping motives. Theoretical and clinical implications as well as future directions regarding the association between distress tolerance and alcohol use motives among trauma exposed persons are discussed. PMID- 22072845 TI - Selection criteria for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer. AB - Peritoneal carcinomatosis in gastric cancer is associated with a dismal prognosis. Systemic chemotherapy is not effective because of the existence of a blood-peritoneal barrier. Cytoreductive surgery and intraperitoneal chemotherapy can improve survival and quality of life in selected patients. Patient selection for this multimodal approach is one of the most critical issues, and calls for interdisciplinary evaluation by radiologists, medical and surgical oncologists, and anaesthetists. This article sets forth criteria for selection of gastric cancer patients suffering from peritoneal carcinomatosis. PMID- 22072846 TI - Distinct colonoscopy findings of microscopic colitis: not so microscopic after all? AB - Microscopic colitis (MC) is considered an "umbrella term", comprising two subtypes, i.e., collagenous colitis (CC) and lymphocytic colitis (LC). They are classically associated with normal or unremarkable colonoscopy. In the last few years, reports have been published revealing findings that are thought to be characteristic or pathognomonic of MC, especially CC. A systematic electronic and manual search of PubMed and EMBASE (to December 2010), for publications on distinct endoscopic findings in MC, resulted in 42 relevant reports for inclusion in this review. Eighty eight patients with collagenous colitis were presented. Only one publication describing a distinct endoscopic pattern in LC was found. Typical findings in CC are alteration of the vascular mucosal pattern, mucosal nodularity, a sequence of change from mucosal defects to mucosal cicatricial lesions, and perhaps (although of doubtful relevance) mucosal pseudomembranes. A causal connection of mucosal defects with the use of lansoprazole seems to exist. Adoption of the proposed lesion description herein is recommended in order to improve homogeneity of future reports. PMID- 22072847 TI - Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease. AB - The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6 mercaptopurine in those unsuccessfully treated with azathioprine; co administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor alpha; 6-TGN administration; desensitization trials; and split dosing of 6-MP. PMID- 22072849 TI - Hepatic steatosis prevents heme oxygenase-1 induction by isoflurane in the rat liver. AB - AIM: To characterize the inductive effects of isoflurane (ISO) on hepatic heme oxygenase-1 (HO-1) in an animal model of hepatic steatosis. METHODS: Lean (LEAN) and obese (FAT) Zucker rats were randomized into 4 groups: 1: LEAN + pentobarbital sodium (PEN); 2: LEAN + ISO; 3: FAT + PEN; 4: FAT + ISO. The animals were mechanically ventilated for 6 h. In vitro analyses of liver tissue included determination of HO-1 mRNA and protein expression as well as measurement of HO enzyme activity and immunohistochemical analyses. RESULTS: Compared to PEN treatment, ISO administration profoundly induced hepatic HO-1 mRNA and protein expression and significantly increased HO enzyme activity in lean Zucker rats. In contrast, no difference in HO-1 gene expression was observed after ISO or PEN anesthesia in obese Zucker rats. CONCLUSION: The present study demonstrates that ISO is an inducer of hepatic HO-1 gene expression in non-steatotic organs but failed to upregulate HO-1 in steatotic livers. PMID- 22072848 TI - Barrett's esophagus with high-grade dysplasia: focus on current treatment options. AB - High-grade dysplasia (HGD) in Barrett's esophagus (BE) is the critical step before invasive esophageal adenocarcinoma. Although its natural history remains unclear, an aggressive therapeutic approach is usually indicated. Esophagectomy represents the only treatment able to reliably eradicate the neoplastic epithelium. In healthy patients with reasonable life expectancy, vagal-sparing esophagectomy, with associated low mortality and low early and late postoperative morbidity, is considered the treatment of choice for BE with HGD. Patients unfit for surgery should be managed in a less aggressive manner, using endoscopic ablation or endoscopic mucosal resection of the entire BE segment, followed by lifelong surveillance. Patients eligible for surgery who present with a long BE segment, multifocal dysplastic lesions, severe reflux symptoms, a large fixed hiatal hernia or dysphagia comprise a challenging group with regard to the appropriate treatment, either surgical or endoscopic. PMID- 22072850 TI - Decreased accumulation of ultrasound contrast in the liver of nonalcoholic steatohepatitis rat model. AB - AIM: To investigate the diagnosis of nonalcoholic steatohepatitis (NASH) using contrast ultrasonography in the NASH rat model. METHODS: The liver in methionine choline-deficient diet (MCDD) rats, a NASH model constructed by feeding an MCDD, was examined by contrast ultrasonography at weeks 2, 4, 8, 12 and 16, with late phase images of contrast ultrasonography (Kupffer imaging) in which contrast enhancement was achieved by incorporation of a contrast agent by Kupffer cells (KCs), and images were compared to those in rats taking a regular chow. RESULTS: Decrease in contrast enhancement was observed first in MCDD rats at week 2. KCs were counted based on immunohistochemistry, but their numbers were not reduced and it was assumed that attenuation of contrast enhancement was attributable to reduced phagocytic activity of the KCs. CONCLUSION: It is suggested that clinical application of contrast ultrasonography may be valuable for non-invasive diagnosis of NASH. PMID- 22072851 TI - Comparative outcome of stapled trans-anal rectal resection and macrogol in the treatment of defecation disorders. AB - AIM: To prospectively assess the efficacy and safety of stapled trans-anal rectal resection (STARR) compared to standard conservative treatment, and whether preoperative symptoms and findings at defecography and anorectal manometry can predict the outcome of STARR. METHODS: Thirty patients (Female, 28; age: 51 +/- 9 years) with rectocele or rectal intussusception, a defecation disorder, and functional constipation were submitted for STARR. Thirty comparable patients (Female, 30; age 53 +/- 13 years), who presented with symptoms of rectocele or rectal intussusception and were treated with macrogol, were assessed. Patients were interviewed with a standardized questionnaire at study enrollment and 38 +/- 18 mo after the STARR procedure or during macrogol treatment. A responder was defined as an absence of the Rome III diagnostic criteria for functional constipation. Defecography and rectoanal manometry were performed before and after the STARR procedure in 16 and 12 patients, respectively. RESULTS: After STARR, 53% of patients were responders; during conservative treatment, 75% were responders. After STARR, 30% of the patients reported the use of laxatives, 17% had intermittent anal pain, 13% had anal leakage, 13% required digital facilitation, 6% experienced defecatory urgency, 6% experienced fecal incontinence, and 6% required re-intervention. During macrogol therapy, 23% of the patients complained of abdominal bloating and 13% of borborygmi, and 3% required digital facilitation. No preoperative symptom, defecographic, or manometric finding predicted the outcome of STARR. Post-operative defecography showed a statistically significant reduction (P < 0.05) of the rectal diameter and rectocele. The post-operative anorectal manometry showed that anal pressure and rectal sensitivity were not significantly modified, and that rectal compliance was reduced (P = 0.01). CONCLUSION: STARR is not better and is less safe than macrogol in the treatment of defecation disorders. It could be considered as an alternative therapy in patients unresponsive to macrogol. PMID- 22072852 TI - Comparison of Milan and UCSF criteria for liver transplantation to treat hepatocellular carcinoma. AB - AIM: To assess the validity of the Milan and University of California San Francisco (UCSF) criteria and examine the long-term outcome of orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) in a single center study. METHODS: This study is a retrospective review of prospectively collected data. Between 1998 and 2009, 56 of 356 OLTs were performed in patients with HCC. Based on pathological examination of liver explants, patients were retrospectively categorized into 3 grou-ps: Milan + (n = 34), Milan -/UCSF + (n = 7) and UCSF - (n = 14). RESULTS: Median follow-up period was 39.5 (1-124) mo. The 5-year overall survival rates in the Milan +, Milan -/UCSF + and UCSF-groups were 87.7%, 53.6% and 33.3%, respectively (P < 0.000). Within these groups, tumor recurrence was determined in 5.8%, 14.3% and 40% of patients, respectively (P < 0.011). Additionally, the presence of microvascular invasion within the explanted liver had a negative effect on the 5-year disease free survival (74.7% vs. 46.7%, P < 0.044). CONCLUSION: The Milan criteria are reliable in the selection of suitable candidates for OLT for the treatment of HCC. For cases of OLT involving living donors, the UCSF criteria may be applied. PMID- 22072853 TI - Efficacy of premedication with activated Dimethicone or N-acetylcysteine in improving visibility during upper endoscopy. AB - AIM: To assess the efficacy of N-acetylcysteine (NAC) and activated Dimethicone in improving endoscopic mucosal visibility. METHODS: A total of 148 patients were randomly allocated into four groups to receive one of the following premedications: group A: 100 mL water alone; group B: activated Dimethicone plus water (up to 100 mL); group C: NAC plus water (up to 100 mL); and group D: activated Dimethicone and NAC plus water (up to 100 mL). A single endoscopist blinded to the patients group assessed the gastric mucosal visibility scores (range 1-4) at four sites. The sum of the scores from the four sites was considered as the total mucosal visibility score (TMVS). RESULTS: The patients in group B showed a significantly lower TMVS than those of groups A and C (P < 0.001). The TMVS in patients of group D was significantly lower than that of groups A and C (P < 0.001). The TMVS did not significantly differ between groups B and D (P > 0.05). The difference between TMVS of groups C and A was not significant (P > 0.05). CONCLUSION: Premedication with activated Dimethicone 20 min prior to the upper endoscopy leads to the best visibility. NAC does not improve visualization by itself. PMID- 22072854 TI - Usefulness of fecal lactoferrin in predicting and monitoring the clinical severity of infectious diarrhea. AB - AIM: To explore the value of fecal lactoferrin in predicting and monitoring the clinical severity of infectious diarrhea. METHODS: Patients with acute infectious diarrhea ranging from 3 mo to 10 years in age were enrolled, and one to three stool samples from each subject were collected. Certain parameters, including white blood cells /differential count, C-reactive protein, fecal mucus, fecal pus cells, duration of fever, vomiting, diarrhea and severity (indicated by Clark and Vesikari scores), were recorded and analyzed. Fecal lactoferrin was determined by enzyme-linked immunosorbent assay and compared in different pathogen and disease activity. Generalized estimating equations (GEE) were also used for analysis. RESULTS: Data included 226 evaluations for 117 individuals across three different time points. Fecal lactoferrin was higher in patients with Salmonella (11.17 MUg/g +/- 2.73 MUg/g) or Campylobacter (10.32 MUg/g +/- 2.94 MUg/g) infections and lower in patients with rotavirus (2.82 MUg/g +/- 1.27 MUg/g) or norovirus (3.16 MUg/g +/- 1.18 MUg/g) infections. Concentrations of fecal lactoferrin were significantly elevated in patients with severe (11.32 MUg/g +/- 3.29 MUg/g) or moderate (3.77 MUg/g +/- 2.08 MUg/g) disease activity compared with subjects with mild (1.51 MUg/g +/- 1.36 MUg/g) disease activity (P < 0.05). GEE analysis suggests that this marker could be used to monitor the severity and course of gastrointestinal infections and may provide information for disease management. CONCLUSION: Fecal lactoferrin increased during bacterial infection and with greater disease severity and may be a good marker for predicting and monitoring intestinal inflammation in children with infectious diarrhea. PMID- 22072855 TI - Aberrant methylation of the 3q25 tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma. AB - AIM: To identify the novel methylation-silenced gene pentraxin 3 (PTX3) in esophageal squamous cell carcinoma (ESCC). METHODS: PTX3 mRNA expression was examined in six human ESCC cell lines, one human immortalized normal esophageal epithelial cell line, primary ESCC tumor tissue, and paired adjacent nontumor tissue using reverse transcription polymerase chain reaction (RT-PCR). Semi quantitative immunohistochemistry was used to examine cellular localisation and protein levels. Methylation specific PCR and bisulphite genomic sequencing were employed to investigate the methylation of the candidate gene. RESULTS: In the majority of ESCC cell lines, we found that PTX3 expression was down-regulated due to gene promoter hypermethylation, which was further confirmed by bisulphite genomic sequencing. Demethylation treatment with 5-aza-2'-deoxycytidine restored PTX3 mRNA expression in ESCC cell lines. Methylation was more common in tumor tissues (85%) than in adjacent nontumor tissues (25%) (P < 0 .01). CONCLUSION: PTX3 is down-regulated through promoter hypermethylation in ESCC, and could potentially serve as a biomarker of ESCC. PMID- 22072856 TI - Role of Kasai procedure in surgery of hilar bile duct strictures. AB - AIM: To assess the application of the Kasai procedure in the surgical management of hilar bile duct strictures. METHODS: Ten consecutive patients between 2005 and 2011 with hilar bile duct strictures who underwent the Kasai procedure were retrospectively analyzed. Kasai portoenterostomy with the placement of biliary stents was performed in all patients. Clinical characteristics, postoperative complications, and long-term outcomes were analyzed. All patients were followed up for 2-60 mo postoperatively. RESULTS: Patients were classified according to the Bismuth classification of biliary strictures. There were two Bismuth III and eight Bismuth IV lesions. Six lesions were benign and four were malignant. Of the benign lesions, three were due to post-cholecystectomy injury, one to trauma, one to inflammation, and one to inflammatory pseudotumor. Of the malignant lesions, four were due to hilar cholangiocarcinoma. All patients underwent Kasai portoenterostomy with the placement of biliary stents. There were no perioperative deaths. One patient experienced anastomotic leak and was managed conservatively. No other complications occurred perioperatively. During the follow-up period, all patients reported a good quality of life. CONCLUSION: The Kasai procedure combined with biliary stents may be appropriate for patients with hilar biliary stricture that cannot be managed by standard surgical methods. PMID- 22072857 TI - Three initial diets for management of mild acute pancreatitis: a meta-analysis. AB - AIM: To compare non-liquid and clear-liquid diets, and to assess whether the latter is the optimal treatment for mild acute pancreatitis. METHODS: The Cochrane Library, PUBMED, EMBASE, EBM review databases, Science Citation Index Expanded, and several Chinese databases were searched up to March 2011. Randomized controlled trials (RCTs) that compared non-liquid with clear-liquid diets in patients with mild acute pancreatitis were included. A meta-analysis was performed using available evidence from RCTs. RESULTS: Three RCTs of adequate quality involving a total of 362 participants were included in the final analysis. Compared to liquid diet, non-liquid diet significantly decreased the length of hospitalization [mean difference (MD): 1.18, 95% CI: 0.82-1.55; P<0.00001] and total length of hospitalization (MD: 1.31, 95% CI: 0.45-2.17; P = 0.003). The subgroup analysis showed solid diet was more favorable than clear liquid diet in the length of hospitalization, with a pooled MD being -1.05 (95% CI: -1.43 to -0.66; P<0.00001). However, compared with clear liquid diet, both soft and solid diets did not show any significant differences for recurrence of pain after re-feeding, either alone [relative risk (RR): 0.95; 95% CI: 0.51-1.87; P = 0.88] and (RR: 1.22; 95% CI: 0.69-2.16; P = 0.49), respectively, or analyzed together as non-liquid diet (RR: 0.80; 95% CI: 0.47-1.36; P = 0.41). CONCLUSION: The non-liquid soft or solid diet did not increase pain recurrence after re feeding, compared with the clear-liquid diet. The non-liquid diet reduced hospitalization. PMID- 22072859 TI - Johanson-Blizzard syndrome. AB - Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, hypoplastic or aplastic nasal alae, cutis aplasia on the scalp, and other features including developmental delay, failure to thrive, hearing loss, mental retardation, hypothyroidism, dental abnormalities, and anomalies in cardiac and genitourinary systems. More than 60 cases of this syndrome have been reported to date. We describe the case of a male infant with typical symptoms of JBS. In addition, a new clinical feature which has not previously been documented, that is anemia requiring frequent blood transfusions and mild to moderate thrombocytopenia was observed. A molecular study was performed which revealed a novel homozygous UBR1 mutation. Possible explanations for this new association are discussed. PMID- 22072858 TI - Integration of human papillomavirus 18 DNA in esophageal carcinoma 109 cells. AB - AIM: To detect human papillomavirus (HPV) DNA in esophageal carcinoma (EC) 109 cells and investigate the relationship between HPV and EC. METHODS: Genomic DNA and total RNA from EC109 cells were isolated. HPV DNA was detected by polymerase chain reaction (PCR) with the general primer sets of My09/11 and GP5 +/6 + for the HPV L1 gene and type-specific primer sets for HPV18 E6 and HPV18 E6-E7. Reverse transcription (RT) of mRNA isolated from EC109 cells was performed to produce a cDNA. And then a PCR-based protocol for the amplification of papillomavirus oncogene transcripts was used to analyze HPV18 DNA and integrated transcripts of HPV18 in the chromosomes of EC109 cells. The final nested PCR products were cloned into a pMD-18T vector and sequenced to analyze the chromosomal location of HPV integration. RESULTS: HPV18 DNA was detected in EC109 cells by PCR using the general primer sets of My09/11 and GP5 +/6 + for HPV L1 and the type-specific primer sets for HPV18 E6 and E6-E7 to generate products of 450 bp, 150 bp, 335 bp and 944 bp, respectively. Approximately 600 bp of integrated HPV18-specific transcript was identified. The final nested PCR product of integrated HPV18 DNA was cloned into a pMD-18T vector and sequenced to analyze the chromosomal location of HPV integration. Sequence alignment showed that the HPV18 sequence from EC109 cells was identical to that of the encoded early protein E7-E1 of the standard HPV18 strain X05015, and another partial gene sequence was identical to a partial sequence of human chromosome 8. CONCLUSION: Integration of the HPV genome into the host cell chromosome suggests that persistent HPV infection is vital for malignant cell transformation and carcinogenesis. PMID- 22072860 TI - Count-Rate Performance of the Discovery STE PET Scanner Using Partial Collimation. AB - We investigated the use of partial collimation on a clinical PET scanner by removing septa from conventional 2D collimators. The goal is to improve noise equivalent count-rates (NEC) compared to 2D and 3D scans for clinically relevant activity concentrations. We evaluated two cases: removing half of the septa (2.5D); and removing two-thirds of the septa (2.7D). System performance was first modeled using the SimSET simulation package, and then measured with the NEMA NU2 2001 count-rate cylinder (20 cm dia., 70 cm long), and 27 cm and 35 cm diameter cylinders of the same length. An image quality phantom was also imaged with the 2.7D collimator. SimSET predicted the relative NEC curves very well, as confirmed by measurements, with 2.5D and 2.7D NEC greater than 2D and 3D NEC in the range of ~5-20 mCi in the phantom. We successfully reconstructed images of the image quality phantom from measured 2.7D data using custom 2.7D normalization. Partial collimation shows promise for optimized clinical imaging in a fixed-collimator system. PMID- 22072861 TI - Simulations of the Effect of Collimation on Count Rates of an LSO PET System. AB - We present a simulation study of the effect of different degrees of collimation on countrate performance of a hypothetical PET scanner with LSO crystals. The simulated scanner is loosely based on the geometry of the Siemens Biograph Hi-Rez scanner.System behavior is studied with a photon tracking simulation package (SimSET).We investigate the NEMA NU2-2001 count rate and scatter fraction behavior for systems with different amounts of collimation, which is achieved by adding septa to the fully-3D system as in clinical use. We study systems with 2, 5, 11, and 40 septa. The effect of collimation is studied for three patient thicknesses.The resulting count rate curves for true, scattered, and random coincidences as well as noise equivalent count rates are compared for the different collimation cases. Improved countrate performance with partial collimation is seen. However, except for the largest diameter phantom, the NEC rate increase is seen at higher activities than those used clinically.The NEC countrate versus activity curves for the LSO systems are also compared to those from a BGO system where partial collimation increases NEC countrate over a clinically relevant activity range. PMID- 22072862 TI - Design and Implementation of a Block Detector Simulation in SimSET. AB - SimSET (a Simulation System for Emission Tomography) is being modified to more accurately simulate typical PET block detector tomographs. A new detector module that models the detector system as a collection of rectangular boxes is being added to the software. The new model is sufficiently general to allow many more imaginative or speculative detector systems to be simulated. PMID- 22072863 TI - Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs. AB - BACKGROUND: Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. METHODS: Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m(2), and subsequent dosages were escalated at 50% (dog 1), 100% (dog 2), or 200% (dog 3) with each cycle, to a maximum of 240 mg/m(2). Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. RESULTS: The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m(2). Grade 1-2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen) toxicity was noted. CONCLUSION: CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m(2). PMID- 22072864 TI - Quantum dot-based quantitative immunofluorescence detection and spectrum analysis of epidermal growth factor receptor in breast cancer tissue arrays. AB - BACKGROUND: The epidermal growth factor receptor (EGFR) is a promising therapeutic target in cancer, but its clinical value in breast cancer remains controversial. Our previous studies have found that quantitative analysis of biomarkers with quantum dot-based nanotechnology had better detection performance than conventional immunohistochemistry. The present study was undertaken to investigate the prognostic value of EGFR in breast cancer using quantum dot-based quantitative spectral analysis. METHODS: EGFR expression in 65 breast cancer specimens was detected by immunohistochemistry and quantum dot immunohistochemistry, and comparisons were made between the two methods. EGFR expression in tissue microarrays of 240 breast cancer patients was then detected by quantum dot-immunohistochemistry and spectral analysis. The prognostic value of EGFR immunofluorescence area (EGFR area) for five-year recurrence-free survival was investigated. RESULTS: The same antigen localization, high correlation of staining rates (r = 0.914), and high agreement of measurement (kappa = 0.848) of EGFR expression in breast cancer were found by quantum dot immunohistochemistry and immunohistochemistry. The EGFR area showed significant differences by tumor grade, lymph node status, HER2 status, and hormone receptor status (all P < 0.05). Patients in the large EGFR area (>= 30.51) group had a significantly higher five-year recurrence rate (47.2% versus 27.4%, P = 0.002) and worse five-year recurrence-free survival (log-rank test, P = 0.0015) than those in the small EGFR area (<30.51) group. In the subgroups, EGFR area was an independent prognosticator in the HER2-positive and lymph node-positive subgroups. CONCLUSION: Quantum dot-based quantitative detection demonstrates the prognostic value of EGFR area in the HER2-positive and lymph node-positive subgroups of invasive breast cancer. PMID- 22072865 TI - Preparation, characterization, and efficient transfection of cationic liposomes and nanomagnetic cationic liposomes. AB - PURPOSE: Cationic liposomes (CLs) are composed of phospholipid bilayers. One of the most important applications of these particles is in drug and gene delivery. However, using CLs to deliver therapeutic nucleic acids and drugs to target organs has some problems, including low transfection efficiency in vivo. The aim of this study was to develop novel CLs containing magnetite to overcome the deficiencies. MATERIALS AND METHODS: CLs and magnetic cationic liposomes (MCLs) were prepared using the freeze-dried empty liposome method. Luciferase-harboring vectors (pGL3) were transferred into liposomes and the transfection efficiencies were determined by luciferase assay. Firefly luciferase is one of most popular reporter genes often used to measure the efficiency of gene transfer in vivo and in vitro. Different formulations of liposomes have been used for delivery of different kinds of gene reporters. Lipoplex (liposome-plasmid DNA complexes) formation was monitored by gel retardation assay. Size and charge of lipoplexes were determined using particle size analysis. Chinese hamster ovary cells were transfected by lipoplexes (liposome-pGL3); transfection efficiency and gene expression level was evaluated by luciferase assay. RESULTS: High transfection efficiency of plasmid by CLs and novel nanomagnetic CLs was achieved. Moreover, lipoplexes showed less cytotoxicity than polyethyleneimine and Lipofectamine. CONCLUSION: Novel liposome compositions (1,2-dipalmitoyl-sn-glycero-3 phosphocholine [DPPC]/dioctadecyldimethylammonium bromide [DOAB] and DPPC/cholesterol/DOAB) with high transfection efficiency can be useful in gene delivery in vitro. MCLs can also be used for targeted gene delivery, due to magnetic characteristic for conduction of genes or drugs to target organs. PMID- 22072866 TI - Novel formulation of a methotrexate derivative with a lipid nanoemulsion. AB - BACKGROUND: Lipid nanoemulsions that bind to low-density lipoprotein receptors can concentrate chemotherapeutic agents in tissues with low-density lipoprotein receptor overexpression and decrease the toxicity of the treatment. The aim of this study was to develop a new formulation using a lipophilic derivative of methotrexate, ie, didodecyl methotrexate (ddMTX), associated with a lipid nanoemulsion (ddMTX-LDE). METHODS: ddMTX was synthesized by an esterification reaction between methotrexate and dodecyl bromide. The lipid nanoemulsion was prepared by four hours of ultrasonication of a mixture of phosphatidylcholine, triolein, and cholesteryloleate. Association of ddMTX with the lipid nanoemulsion was performed by additional cosonication of ddMTX with the previously prepared lipid nanoemulsion. Formulation stability was evaluated, and cell uptake, cytotoxicity, and acute animal toxicity studies were performed. RESULTS: The yield of ddMTX incorporation was 98% and the particle size of LDE-ddMTX was 60 nm. After 48 hours of incubation with plasma, approximately 28% ddMTX was released from the lipid nanoemulsion. The formulation remained stable for at least 45 days at 4 degrees C. Cytotoxicity of LDE-ddMTX against K562 and HL60 neoplastic cells was higher than for methotrexate (50% inhibitory concentration [IC(50)] 1.6 versus 18.2 mM and 0.2 versus 26 mM, respectively), and cellular uptake of LDE-ddMTX was 90-fold higher than that of methotrexate in K562 cells and 75-fold in HL60 cells. Toxicity of LDE-ddMTX, administered at escalating doses, was higher than for methotrexate (LD(50) 115 mg/kg versus 470 mg/kg; maximum tolerated dose 47 mg/kg versus 94 mg/kg) in mice. However, the hematological toxicity of LDE-ddMTX was lower than for methotrexate. CONCLUSION: LDE-ddMTX was stable, and uptake of the formulation by neoplastic cells was remarkably greater than of methotrexate, which resulted in markedly greater cytotoxicity. LDE-ddMTX is thus a promising formulation to be tested in future animal models of cancer or rheumatic disease, wherein methotrexate is widely used. PMID- 22072867 TI - Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions. AB - OBJECTIVES: Cholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated. METHODS: Eighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections. RESULTS: LDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase IIalpha and tubulin). CONCLUSION: The ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease. PMID- 22072868 TI - Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer. AB - BACKGROUND: Nanomaterials are considered to be the pre-eminent component of the rapidly advancing field of nanotechnology. However, developments in the biologically inspired synthesis of nanoparticles are still in their infancy and consequently attracting the attention of material scientists throughout the world. Keeping in mind the fact that microorganism-assisted synthesis of nanoparticles is a safe and economically viable prospect, in the current study we report Candida albicans-mediated biological synthesis of gold nanoparticles. METHODS AND RESULTS: Transmission electron microscopy, atomic force microscopy, and various spectrophotometric analyses were performed to characterize the gold nanoparticles. The morphology of the synthesized gold particles depended on the abundance of C. albicans cytosolic extract. Transmission electron microscopy, nanophox particle analysis, and atomic force microscopy revealed the size of spherical gold nanoparticles to be in the range of 20-40 nm and nonspherical gold particles were found to be 60-80 nm. We also evaluated the potential of biogenic gold nanoparticles to probe liver cancer cells by conjugating them with liver cancer cell surface-specific antibodies. The antibody-conjugated gold particles were found to bind specifically to the surface antigens of the cancer cells. CONCLUSION: The antibody-conjugated gold particles synthesized in this study could successfully differentiate normal cell populations from cancerous cells. PMID- 22072869 TI - Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. AB - BACKGROUND: Doxorubicin has a broad spectrum of anticancer activity, but its clinical application is limited due to serious side effects. The aim of this study was to explore a novel drug delivery system based on titanium dioxide (TiO(2)) nanoparticles for its potential role in enhancing the anticancer efficacy of doxorubicin while reducing its side effects. METHODS AND RESULTS: Doxorubicin was loaded into TiO(2) nanoparticles by forming complexes with the transition metal, titanium, to construct doxorubicin-titanium dioxide (DOX TiO(2)) nanocomposites as a drug delivery system. The anticancer activity of the DOX-TiO(2) nanocomposites was demonstrated by MTT assay, and the possible signaling pathway was explored by Western blot. In human SMMC-7721 hepatocarcinoma cells, our observations demonstrated that this drug delivery system markedly increased the efficiency of drug per dosage and decreased the IC(50), resulting in anticancer efficacy enhancement and side effect attenuation. CONCLUSION: Such a doxorubicin delivery strategy is promising in cancer therapy. Apoptosis may contribute to the mechanism, due to protein expression of Bcl-2 being downregulated and that of Bax and caspase 3 being upregulated. PMID- 22072870 TI - Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats. AB - BACKGROUND: Cerium oxide (CeO(2)) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO(2) nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. METHODS AND RESULTS: Compared with control animals, CeO(2) nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO(2) nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO(2) nanoparticles. CONCLUSION: Taken together, these data suggest that intratracheal instillation of CeO(2) nanoparticles can result in liver damage. PMID- 22072871 TI - Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy. AB - BACKGROUND: We report here a unique approach to using multifunctional dendrimer/combretastatin A4 (CA4) inclusion complexes for targeted cancer therapeutics. METHODS: Amine-terminated generation 5 polyamidoamine dendrimers were first partially acetylated to neutralize a significant portion of the terminal amines, and then the remaining dendrimer terminal amines were sequentially modified with fluorescein isothiocyanate as an imaging agent and folic acid as a targeting ligand. The multifunctional dendrimers formed (G5.NHAc FI-FA) were utilized to encapsulate the anticancer drug, CA4, for targeted delivery into cancer cells overexpressing folic acid receptors. RESULTS: The inclusion complexes of G5.NHAc-FI-FA/CA4 formed were stable and are able to significantly improve the water solubility of CA4 from 11.8 to 240 MUg/mL. In vitro release studies showed that the multifunctional dendrimers complexed with CA4 could be released in a sustained manner. Both 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide colorimetric assay and morphological cell observation showed that the inhibitory effect of the G5.NHAc-FI-FA/CA4 complexes was similar to that of free CA4 at the same selected drug concentration. More importantly, the complexes were able to target selectively and display specific therapeutic efficacy to cancer cells overexpressing high-affinity folic acid receptors. CONCLUSION: Multifunctional dendrimers may serve as a valuable carrier to form stable inclusion complexes with various hydrophobic anticancer drugs with improved water solubility, for targeting chemotherapy to different types of cancer. PMID- 22072873 TI - Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm. AB - Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ) against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN) suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4 degrees C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% +/- 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 +/- 11.15 nm, 0.34 +/- 0.06, and -11.57 +/- 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4 degrees C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91.55%, 87.5%, and 66.7%. When the dose reduced to 0.5 mg/kg, the native drug showed no effect, but the suspension still got the same therapeutic efficacy as that of the 5 mg/kg native PZQ. These results demonstrate that the PZQ-HCO-SLN suspension is a promising formulation to enhance the therapeutic efficacy of PZQ. PMID- 22072872 TI - Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations. AB - BACKGROUND: Inhaled corticosteroids provide unique systems for local treatment of asthma or chronic obstructive pulmonary disease. However, the use of poorly soluble drugs for nebulization has been inadequate, and many patients rely on large doses to achieve optimal control of their disease. Theoretically, nanotechnology with a sustained-release formulation may provide a favorable therapeutic index. The aim of this study was to determine the feasibility of using sterically stabilized phospholipid nanomicelles of budesonide for pulmonary delivery via nebulization. METHODS: PEG(5000)-DSPE polymeric micelles containing budesonide (BUD-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and pharmacodynamic characteristics of BUD-SSMs were investigated. RESULTS: The optimal concentration of solubilized budesonide at 5 mM PEG(5000)-DSPE was 605.71 +/- 6.38 MUg/mL, with a single-sized peak population determined by photon correlation spectroscopy and a particle size distribution of 21.51 +/- 1.5 nm. The zeta potential of BUD-SSMs was -28.43 +/- 1.98 mV. The percent entrapment efficiency, percent yield, and percent drug loading of the lyophilized formulations were 100.13% +/- 1.09%, 97.98% +/- 1.95%, and 2.01% +/- 0.02%, respectively. Budesonide was found to be amorphous by differential scanning calorimetry, and had no chemical interaction with PEGylated polymer according to Fourier transform infrared spectroscopy. Transmission electron microscopic images of BUD-SSMs revealed spherical nanoparticles. BUD SSMs exhibited prolonged dissolution behavior compared with Pulmicort Respules (P < 0.05). Aerodynamic characteristics indicated significantly higher deposition in the lungs compared with Pulmicort Respules. The mass median aerodynamic, geometric standard deviation, percent emitted dose, and the fine particle fraction were 2.83 +/- 0.08 MUm, 2.33 +/- 0.04 MUm, 59.13% +/- 0.19%, and 52.31% +/- 0.25%, respectively. Intratracheal administration of BUD-SSMs 23 hours before challenge (1 mg/kg) in an asthmatic/chronic obstructive pulmonary disease rat model led to a significant reduction in inflammatory cell counts (76.94 +/- 5.11) in bronchoalveolar lavage fluid compared with administration of Pulmicort Respules (25.06 +/- 6.91). CONCLUSION: The BUD-SSMs system might be advantageous for asthma or chronic obstructive pulmonary disease and other inflammatory airway diseases. PMID- 22072874 TI - Manufacturing of biodegradable polyurethane scaffolds based on polycaprolactone using a phase separation method: physical properties and in vitro assay. AB - BACKGROUND: Biodegradable polyurethanes have found widespread use in soft tissue engineering due to their suitable mechanical properties and biocompatibility. METHODS: In this study, polyurethane samples were synthesized from polycaprolactone, hexamethylene diisocyanate, and a copolymer of 1,4-butanediol as a chain extender. Polyurethane scaffolds were fabricated by a combination of liquid-liquid phase separation and salt leaching techniques. The effect of the NCO:OH ratio on porosity content and pore morphology was investigated. RESULTS: Scanning electron micrographs demonstrated that the scaffolds had a regular distribution of interconnected pores, with pore diameters of 50-300 MUm, and porosities of 64%-83%. It was observed that, by increasing the NCO:OH ratio, the average pore size, compressive strength, and compressive modulus increased. L929 fibroblast and chondrocytes were cultured on the scaffolds, and all samples exhibited suitable cell attachment and growth, with a high level of biocompatibility. CONCLUSION: These biodegradable polyurethane scaffolds demonstrate potential for soft tissue engineering applications. PMID- 22072875 TI - Molecular network topology and reliability for multipurpose diagnosis. AB - This investigation proposes the use of molecular network topology for drug delivery and diagnosis network design. Three modules of molecular network topologies, such as bus, star, and ring networks, are designed and manipulated based on a micro- and nanoring resonator system. The transportation of the trapping molecules by light in the network is described and the theoretical background is reviewed. The quality of the network is analyzed and calculated in terms of signal transmission (ie, signal to noise ratio and crosstalk effects). Results obtained show that a bus network has advantages over star and ring networks, where the use of mesh networks is possible. In application, a thin film network can be fabricated in the form of a waveguide and embedded in artificial bone, which can be connected to the required drug targets. The particular drug/nutrient can be transported to the required targets via the particular network used. PMID- 22072876 TI - The comparison of protein-entrapped liposomes and lipoparticles: preparation, characterization, and efficacy of cellular uptake. AB - Fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA)-loaded polyethylene glycol (PEG)-modified liposomes and lipoparticles with high protein entrapment were developed. The lipid formula of the liposomes contained PEGylated lipids and unsaturated fatty acids for enhancing membrane fluidity and effective delivery into cells. The preparation techniques, lipid content, and PEG-modified lipoparticle ratios were evaluated. The PEG-modified lipoparticles prepared by ethanol injection extrusion (100 nm pore size) achieve a population of blank liposomes with a mean size of 125 +/- 2.3 nm and a zeta potential of -12.4 +/- 1.5 mV. The average particle size of the PEG-modified lipoparticles was 133.7 +/- 8.6 nm with a zeta potential of +13.3 mV. Lipoparticle conformation was determined using transmission electron microscopy and field-emission scanning electron microscopy. The FITC-BSA encapsulation efficiency was dramatically increased from 19.0% for liposomes to 59.7% for lipoparticles. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results confirmed the preparation process, and an 8-hour leaching test did not harm the protein structure. Once prepared, the physical and chemical stability of the PEG-modified lipoparticle formulations was satisfactory over 90 days. In vitro retention tests indicated that the 50% retention time for the protein-containing lipoparticles was 7.9 hours, substantially longer than the liposomes at 3.3 hours. A Caco-2 cell model was used for evaluating the cytotoxicity and cell uptake efficiency of the PEG-modified lipoparticles. At a lipid content below 0.25 mM, neither the liposomes nor the lipoparticles caused significant cellular cytotoxicity (P < 0.01) and FITC-BSA was significantly taken up into cells within 60 minutes (P < 0.01). PMID- 22072877 TI - Gene therapy for C-26 colon cancer using heparin-polyethyleneimine nanoparticle mediated survivin T34A. AB - BACKGROUND: Gene therapy provides a novel method for the prevention and treatment of cancer, but the clinical application of gene therapy is restricted, mainly because of the absence of an efficient and safe gene delivery system. Recently, we developed a novel nonviral gene carrier, ie, heparin-polyethyleneimine (HPEI) nanoparticles for this purpose. METHODS AND RESULTS: HPEI nanoparticles were used to deliver plasmid-expressing mouse survivin-T34A (ms-T34A) to treat C-26 carcinoma in vitro and in vivo. According to the in vitro studies, HPEI nanoparticles could efficiently transfect the pGFP report gene into C-26 cells, with a transfection efficiency of 30.5% +/- 2%. Moreover, HPEI nanoparticle mediated ms-T34A could efficiently inhibit the proliferation of C-26 cells by induction of apoptosis in vitro. Based on the in vivo studies, HPEI nanoparticles could transfect the Lac-Z report gene into C-26 cells in vivo. Intratumoral injection of HPEI nanoparticle-mediated ms-T34A significantly inhibited growth of subcutaneous C-26 carcinoma in vivo by induction of apoptosis and inhibition of angiogenesis. CONCLUSION: This research suggests that HPEI nanoparticle-mediated ms-T34A may have a promising role in C-26 colon carcinoma therapy. PMID- 22072878 TI - Eudragit nanoparticles containing genistein: formulation, development, and bioavailability assessment. AB - BACKGROUND: Genistein, one of the major isoflavones, has received great attention as a phytoestrogen and potential cancer chemoprevention agent. However, the dissolution and bioavailability of genistein from solid oral preparations is low due to its poor water solubility. METHODS: In order to improve the oral bioavailability of genistein, genistein nanoparticles were prepared by the nanoprecipitation technique using Eudragit((r)) E100 as carriers and an optimized formulation of mass ratio (genistein:Eudragit E100, 1:10). The mean particle size of genistein nanoparticles was approximately 120 nm when diluted 100 times with distilled water. The drug-loaded nanoparticles were spherical on observation by transmission electric microscopy. RESULTS: Encapsulation efficiency and drug loading of the genistein nanoparticles were approximately 50.61% and 5.02%, respectively. Release of drug from the genistein nanoparticles was two times greater than that from the conventional capsules. After administration of genistein suspension or genistein nanoparticles at a single dose of 100 mg/kg to fasted rats, the relative bioavailability of genistein from the nanoparticles compared with the reference suspension was 241.8%. CONCLUSION: These results suggested that a nanoparticle system is a potentially promising formulation for the efficient delivery of poorly water-soluble drugs by oral administration. PMID- 22072879 TI - Quantum dots affect expression of CD133 surface antigen in melanoma cells. AB - BACKGROUND: In novel treatment approaches, therapeutics should be designed to target cancer stem cells (CSCs). Quantum dots (QDs) are a promising new tool in fighting against cancer. However, little is known about accumulation and cytotoxicity of QDs in CSCs. METHODS: Accumulation and cytotoxicity of CdTe-MPA (mercaptopropionic acid) QDs in CSCs were assessed using flow cytometry and fluorescence-activated cell sorting techniques as well as a colorimetric cell viability assay. RESULTS: We investigated the expression of two cell surface associated glycoproteins, CD44 and CD133, in four different cancer cell lines (glioblastoma, melanoma, pancreatic, and prostate adenocarcinoma). Only the melanoma cells were positive to both markers of CD44 and CD133, whereas the other cells were only CD44-positive. The QDs accumulated to a similar extent in all subpopulations of the melanoma cells. The phenotypical response after QD treatment was compared with the response after ionizing radiation treatment. The percentage of the CD44(high-)CD133(high) subpopulation decreased from 72% to 55% 58% for both treatments. The stem-like subpopulation CD44(high)CD133(low/-) increased from 26%-28% in the untreated melanoma cells to 36%-40% for both treatments. CONCLUSION: Treatment of melanoma cells with QDs results in an increase of stem-like cell subpopulations. The changes in phenotype distribution of the melanoma cells after the treatment with QDs are comparable with the changes after ionizing radiation. PMID- 22072880 TI - In situ formation of nanocrystals from a self-microemulsifying drug delivery system to enhance oral bioavailability of fenofibrate. AB - OBJECTIVES: In situ formation of nanocrystals and dissolution profiles of fenofibrate (FFB) from a self-microemulsifying drug delivery system (SMEDDS) were characterized. METHODS: SMEDDS formulated with Myritol and surfactant mixture (Smix) of D-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and either Tween 20 (A, C, E, G, M, S, N, T, O) or Tween 80 (B, D, F, H, P, U, Q, V, R) at various oil/Smix ratios (Group I: A and B of 0.42, C and D of 0.25, E and F of 0.11; Group II: G and H of 1.38, M and P of 1.11, S and U of 0.9, N and Q of 0.73, T and V of 0.58, and O and R of 0.46) and water contents (1: 9.5%, 2: 5.0%, 3: 0.0%, G-V: 4.5%). Their dissolutions were conducted at different rotation speeds. Two optimal SMEDDSs containing Tween 80(B2) or a higher oil/Smix ratio(Q) and B2(solution) were selected for pharmacokinetic study. RESULTS: FFB particles formed within the nanosize range from Group I gradually increased with time but decreased with increasing stirring rates. However, the mean size of FFB formed by B series was as low as 200 nm, which was smaller than that of A series at three stirring rates. The release rate from both groups obviously increased with increasing stirring rate. However, incomplete release was observed for S and N in Tween 20 series, whereas a faster release rate and complete release were observed for Tween 80 series with an insignificant difference among them. Results of pharmacokinetic study demonstrated that the highest-ranked area under the curve and Cmax values were for Q(SMEDDS) and B2(solution), respectively. The relative bioavailability of Q(SMEDDS) with respect to Tricor was enhanced by about 1.14 1.22-fold. CONCLUSION: SMEDDS, consisting of Myritol 318 and TPGS combined with Tween 80 at 4:1, was able to enhance the oral bioavailability of FFB. PMID- 22072881 TI - Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice. AB - BACKGROUND: The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide admixed elastic liposomes (EL/T). METHODS: HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed. RESULTS: EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase 2, IL-4, IL-13, immunoglobulin E, and eosinophils. CONCLUSION: A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD. PMID- 22072882 TI - Enhanced transdermal delivery of evodiamine and rutaecarpine using microemulsion. AB - OBJECTIVE: The purpose of this study was to improve skin permeation of evodiamine and rutaecarpine for transdermal delivery with microemulsion as vehicle and investigate real-time cutaneous absorption of the drugs via in vivo microdialysis. METHODS: Pseudoternary phase diagrams were constructed to evaluate microemulsion regions with various surfactants and cosurfactants. Nine formulations of oil in water microemulsions were selected as vehicles for assessing skin permeation of evodiamine and rutaecarpine in ex vivo transdermal experiments. With a microdialysis hollow fiber membrane implanted in the skin beneath the site of topical drug administration, dialysis sampling was maintained for 10 hours and the samples were detected directly by high performance liquid chromatography. Real-time concentrations of the drugs in rat skin were investigated and compared with those of conventional formulations, such as ointment and tincture. Furthermore, the drugs were applied to various regions of the skin using microemulsion as vehicle. RESULTS: In ex vivo transdermal experiments, cutaneous fluxes of evodiamine and rutaecarpine microemulsions were 2.55-fold to 11.36-fold and 1.17-fold to 6.33-fold higher, respectively, than those of aqueous suspensions. Different drug loadings, microemulsion water content, and transdermal enhancers markedly influenced the permeation of evodiamine and rutaecarpine. In microemulsion application with in vivo microdialysis, the maximum concentration of the drugs (evodiamine: 18.23 +/- 1.54 ng/mL; rutaecarpine: 16.04 +/- 0.69 ng/mL) were the highest, and the area under the curve(0-t) of evodiamine and rutaecarpine was 1.52-fold and 2.27-fold higher than ointment and 3.06-fold and 4.23-fold higher than tincture, respectively. A greater amount of drugs penetrated through and was absorbed by rat abdominal skin than shoulder and chest, and a reservoir in the skin was found to supply drugs even after the microemulsion was withdrawn. CONCLUSION: Compared to conventional formulations, higher cutaneous fluxes of evodiamine and rutaecarpine were achieved with microemulsion. Based on this novel transdermal delivery, the transdermal route was effective for the administration of the two active alkaloids. PMID- 22072883 TI - Skeletal myotube formation enhanced by electrospun polyurethane carbon nanotube scaffolds. AB - BACKGROUND: This study examined the effects of electrically conductive materials made from electrospun single- or multiwalled carbon nanotubes with polyurethane to promote myoblast differentiation into myotubes in the presence and absence of electrical stimulation. METHODS AND RESULTS: After electrical stimulation, the number of multinucleated myotubes on the electrospun polyurethane carbon nanotube scaffolds was significantly larger than that on nonconductive electrospun polyurethane scaffolds (5% and 10% w/v polyurethane). In the absence of electrical stimulation, myoblasts also differentiated on the electrospun polyurethane carbon nanotube scaffolds, as evidenced by expression of Myf-5 and myosin heavy chains. The myotube number and length were significantly greater on the electrospun carbon nanotubes with 10% w/v polyurethane than on those with 5% w/v polyurethane. The results suggest that, in the absence of electrical stimulation, skeletal myotube formation is dependent on the morphology of the electrospun scaffolds, while with electrical stimulation it is dependent on the electrical conductivity of the scaffolds. CONCLUSION: This study indicates that electrospun polyurethane carbon nanotubes can be used to modulate skeletal myotube formation with or without application of electrical stimulation. PMID- 22072884 TI - Formulation and in vitro release evaluation of newly synthesized palm kernel oil esters-based nanoemulsion delivery system for 30% ethanolic dried extract derived from local Phyllanthus urinaria for skin antiaging. AB - BACKGROUND: Recently there has been a remarkable surge of interest about natural products and their applications in the cosmetic industry. Topical delivery of antioxidants from natural sources is one of the approaches used to reverse signs of skin aging. The aim of this research was to develop a nanoemulsion cream for topical delivery of 30% ethanolic extract derived from local Phyllanthus urinaria (P. urinaria) for skin antiaging. METHODS: Palm kernel oil esters (PKOEs)-based nanoemulsions were loaded with P. urinaria extract using a spontaneous method and characterized with respect to particle size, zeta potential, and rheological properties. The release profile of the extract was evaluated using in vitro Franz diffusion cells from an artificial membrane and the antioxidant activity of the extract released was evaluated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method. RESULTS: Formulation F12 consisted of wt/wt, 0.05% P. urinaria extract, 1% cetyl alcohol, 0.5% glyceryl monostearate, 12% PKOEs, and 27% Tween 80/Span 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and a 59.5% phosphate buffer system at pH 7.4. Formulation F36 was comprised of 0.05% P. urinaria extract, 1% cetyl alcohol, 1% glyceryl monostearate, 14% PKOEs, 28% Tween 80/Span 80 (9/1) with a hydrophilic lipophilic balance of 13.9, and 56% phosphate buffer system at pH 7.4 with shear thinning and thixotropy. The droplet size of F12 and F36 was 30.74 nm and 35.71 nm, respectively, and their nanosizes were confirmed by transmission electron microscopy images. Thereafter, 51.30% and 51.02% of the loaded extract was released from F12 and F36 through an artificial cellulose membrane, scavenging 29.89% and 30.05% of DPPH radical activity, respectively. CONCLUSION: The P. urinaria extract was successfully incorporated into a PKOEs based nanoemulsion delivery system. In vitro release of the extract from the formulations showed DPPH radical scavenging activity. These formulations can neutralize reactive oxygen species and counteract oxidative injury induced by ultraviolet radiation and thereby ameliorate skin aging. PMID- 22072885 TI - Folate receptor-targeted fluorescent paramagnetic bimodal liposomes for tumor imaging. AB - RATIONALE AND OBJECTIVE: Receptor-targeted delivery of imaging and therapeutic agents can lead to enhanced efficacy for both. Multimodality imaging offers unique advantages over traditional single modality imaging. Tumor marker folate receptor (FR)-targeted fluorescent paramagnetic bimodal liposomes were synthesized to co-deliver paramagnetic and fluorescence agents for magnetic resonance (MR) and optical bimodal imaging contrast enhancement. MATERIALS AND METHODS: Fluorescent and paramagnetic bimodal liposomes were synthesized with a mean diameter of 136 nm and a low polydispersity index. The liposomes incorporated folate-PEG(3350)-CHEMS for FR targeting, Gd(III)[N,N-Bis stearylamidomethyl-N'-amidomethyl]diethylenetriamine tetraacetic acid (Gd-DTPA BSA) for MR contrast, and calcein for fluorescence. To determine the specificity and efficiency of delivery, the liposomes were evaluated in FR-positive KB and HeLa cells and FR-negative A549 cells, which were analyzed by fluorescence microscopy, magnetic resonance imaging (MRI), and flow cytometry (FCM). RESULTS: FR-specific and efficient cellular uptake of the FR-targeted bimodal liposomes was confirmed by fluorescence microscopy and by FCM. The mean fluorescence intensity (MFI) of KB cells treated with FR-targeted liposomes was 45* that of cells treated with nontargeted liposomes, and 18* that of cells treated with FR targeted liposomes and excess folic acid (FA). The MFI of HeLa cells treated with targeted liposomes was 33* that of nontargeted liposomes, and was 16* that of the mixture of targeted liposomes and free FA. In contrast, the MFI of A549 cells treated with FR-targeted liposomes was nearly the same as those treated with nontargeted liposomes. The T(1)-weighted MR images of HeLa and KB cells incubated with FR-targeted liposomes had much higher signal intensity than those treated with nontargeted liposomes or free Gd-DTPA. Furthermore, the FR-targeting effect could be blocked by excess free FA. CONCLUSION: FR-targeted fluorescent paramagnetic bimodal liposomes provided a novel platform for bimodal tumor imaging and theranostic delivery. PMID- 22072886 TI - Biomimetic component coating on 3D scaffolds using high bioactivity of mesoporous bioactive ceramics. AB - BACKGROUND: Mesoporous bioactive glasses (MBGs) are very attractive materials for use in bone tissue regeneration because of their extraordinarily high bone forming bioactivity in vitro. That is, MBGs may induce the rapid formation of hydroxy apatite (HA) in simulated body fluid (SBF), which is a major inorganic component of bone extracellular matrix (ECM) and comes with both good osteoconductivity and high affinity to adsorb proteins. Meanwhile, the high bioactivity of MBGs may lead to an abrupt initial local pH variation during the initial Ca ion-leaching from MBGs at the initial transplant stage, which may induce unexpected negative effects on using them in in vivo application. In this study we suggest a new way of using MBGs in bone tissue regeneration that can improve the strength and make up for the weakness of MBGs. We applied the outstanding bone-forming bioactivity of MBG to coat the main ECM components HA and collagen on the MBG-polycarplolactone (PCL) composite scaffolds for improving their function as bone scaffolds in tissue regeneration. This precoating process can also expect to reduce initial local pH variation of MBGs. METHODS AND MATERIALS: The MBG-PCL scaffolds were immersed in the mixed solution of the collagen and SBF at 37 degrees C for 24 hours. The coating of ECM components on the MBG-PCL scaffolds and the effect of ECM coating on in vitro cell behaviors were confirmed. RESULTS: The ECM components were fully coated on MBG-PCL scaffolds after immersing in SBF containing dilute collagen-I solution only for 24 hours due to the high bone-forming bioactivity of MBG. Both cell affinity and osteoconductivity of MBG-PCL scaffolds were dramatically enhanced by this precoating process. CONCLUSION: The precoating process of ECM components on MBG PCL scaffold using a high bioactivity of MBG was not only effective in enhancing the functionality of scaffolds but also effective in eliminating the unexpected side effect. The MBG-PCL scaffold-coated ECM components ideally satisfied the required conditions of scaffold in tissue engineering, including 3D well interconnected pore structures with high porosity, good bioactivity, enhanced cell affinity, biocompatibility, osteoconductivity, and sufficient mechanical properties, and promise excellent potential application in the field of biomaterials. PMID- 22072887 TI - PLLA-PEG-TCH-labeled bioactive molecule nanofibers for tissue engineering. AB - By mimicking the native extracellular matrix, electrospun nanofibrous scaffolds (ENSs) can provide both chemical and physical cues to modulate cell adherence and differentiation and to promote tissue regeneration while retaining bioresorbable and biocompatible properties. In this study, ENSs were developed to deliver multiple biomolecules by loading them into the core-sheath structure and/or by conjugating them to the nanofiber surfaces. In this work, poly(L-lactide) poly(ethylene glycol)-NH(2) and poly(L-lactide) were emulsion electrospun into nanofibers with a core-sheath structure. A model drug, tetracycline hydrochloride, was loaded within the nanofibers. Amino and carboxyl reactive groups were then activated on the fiber surfaces using saturated water vapor exposure and base hydrolysis, respectively. These reactive groups allowed the surface of the ENS to be functionalized with two other bioactive molecules, fluorescein isothiocyanate- and rhodamine-labeled bovine serum albumins, which were used as model proteins. The ENSs were shown to retain their antimicrobial capacity after two functionalization reactions, indicating that multifunctional nanofibers can potentially be developed into functional wound dressings or periodontal membranes or used in more complicated tissue systems where multiple growth factors and anti-infection precautions are critical for the successful implantation and regeneration of tissues. PMID- 22072889 TI - Development and optimization of oil-filled lipid nanoparticles containing docetaxel conjugates designed to control the drug release rate in vitro and in vivo. AB - THREE DOCETAXEL (DX) LIPID CONJUGATES: 2'-lauroyl-docetaxel (C12-DX), 2'-stearoyl docetaxel (C18-DX), and 2'-behenoyl-docetaxel (C22-DX) were synthesized to enhance drug loading, entrapment, and retention in liquid oil-filled lipid nanoparticles (NPs). The three conjugates showed ten-fold higher solubility in the liquid oil phase Miglyol 808 than DX. To further increase the drug entrapment efficiency in NPs, orthogonal design was performed. The optimized formulation was composed of Miglyol 808, Brij 78, and Vitamin E tocopheryl polyethylene glycol succinate (TPGS). The conjugates were successfully entrapped in the reduced surfactant NPs with entrapment efficiencies of about 50%-60% as measured by gel permeation chromatography (GPC) at a final concentration of 0.5 mg/mL. All three conjugates showed 45% initial burst release in 100% mouse plasma. Whereas C12-DX showed another 40% release over the next 8 hours, C18-DX and C22-DX in NPs showed no additional release after the initial burst of drug. All conjugates showed significantly lower cytotoxicity than DX in human DU-145 prostate cancer cells. The half maximal inhibitory concentration values (IC(50)) of free conjugates and conjugate NPs were comparable except for C22-DX, which was nontoxic in the tested concentration range and showed only vehicle toxicity when entrapped in NPs. In vivo, the total area under the curve (AUC(0-infinity)) values of all DX conjugate NPs were significantly greater than that of Taxotere, demonstrating prolonged retention of drug in the blood. The AUC(0-infinity) value of DX in Taxotere was 8.3-fold, 358.0-fold, and 454.5-fold lower than that of NP-formulated C12-DX, C18 DX, and C22-DX, respectively. The results of these studies strongly support the idea that the physical/chemical properties of DX conjugates may be fine-tuned to influence the affinity and retention of DX in oil-filled lipid NPs, which leads to very different pharmacokinetic profiles and blood exposure of an otherwise potent chemo-therapeutic agent. These studies and methodologies may allow for improved and more potent nanoparticle-based formulations. PMID- 22072890 TI - Physicochemical properties and biocompatibility of a polymer-paclitaxel conjugate for cancer treatment. AB - BACKGROUND: Poly(L-gamma-glutamylglutamine) paclitaxel (PGG-PTX) conjugate is a non-diblock polymeric drug nanoparticle intended to improve the therapeutic index of paclitaxel. The purpose of the present study was to elucidate further the physicochemical properties of PGG-PTX in order to proceed with its clinical development. METHODS AND RESULTS: PGG-PTX was designed by integration of a hydrophobic paclitaxel conjugate through an added hydrophilic glutamic acid onto poly(L-glutamic acid). The addition of a flexible glutamic linker between PGA and paclitaxel resulted in spontaneous self-assembly of a PGG-PTX conjugate into nanoparticles. The PGG-PTX conjugate was stable as a lyophilized solid form. An in vitro viability experiment showed that PGG-PTX was effective after a longer incubation period, the same trend as Taxol. In vitro studies using NCI-H460 and B16F0 cancer cells demonstrated significantly high cellular uptake after 30 minutes of incubation. The in vivo biocompatibility of PGG-PTX conjugate was evaluated in the NCI-H460 tumor model, the assessment of tissue seemed to be normal after 21 days of treatment. CONCLUSION: These results are encouraging for further development of non-block polymeric paclitaxel nanoparticles for treatment of cancer. PMID- 22072891 TI - Consistent group selection in high-dimensional linear regression. AB - In regression problems where covariates can be naturally grouped, the group Lasso is an attractive method for variable selection since it respects the grouping structure in the data. We study the selection and estimation properties of the group Lasso in high-dimensional settings when the number of groups exceeds the sample size. We provide sufficient conditions under which the group Lasso selects a model whose dimension is comparable with the underlying model with high probability and is estimation consistent. However, the group Lasso is, in general, not selection consistent and also tends to select groups that are not important in the model. To improve the selection results, we propose an adaptive group Lasso method which is a generalization of the adaptive Lasso and requires an initial estimator. We show that the adaptive group Lasso is consistent in group selection under certain conditions if the group Lasso is used as the initial estimator. PMID- 22072892 TI - Antioxidant properties of the edible Basidiomycete Armillaria mellea in submerged cultures. AB - Antioxidant components, ascorbic acid, total flavonoids and total phenols are produced effectively by Armillaria mellea submerged cultures. Dried mycelia and mycelia-free broths obtained by A. mellea submerged cultures are extracted with methanol and hot water and investigated for antioxidant properties. Methanolic extracts from dried mycelia (MEM) and mycelia-free broth (MEB) and hot water extracts from dried mycelia (HWEM) by A. mellea submerged cultures show good antioxidant properties as evidenced by low EC(50) values (<10 mg/mL). Total flavonoid is mainly found in hot water extracts; however, total phenol is rich in methanol and hot water extracts from mycelia. Ascorbic acid and total phenol contents are well correlated with the reducing power and the scavenging effect on superoxide anions. Total flavonoid content is dependent on the antioxidant activity and the chelating effect on ferrous ions. Total antioxidant component contents are closely related to the antioxidant activity and the scavenging superoxide anion ability. Results confirm that extracts with good antioxidant properties from fermenting products by A. mellea are potential good substitutes for synthetic antioxidants and can be applied to antioxidant-related functional food and pharmaceutical industries. PMID- 22072893 TI - Assessment of Tamarindus indica extracts for antibacterial activity. AB - Ethanolic and aqueous (hot and cold) extracts of the fruit pulp, stem bark and leaves of Tamarindus indica were evaluated for antibacterial activity, in vitro, against 13 Gram negative and 5 Gram positive bacterial strains using agar well diffusion and macro broth dilution techniques, simultaneously. The fruit pulp extracts exhibited a wide spectrum of activity; the cold water extract against 95.5% of the test bacterial strains; and the hot water and ethanolic extracts against 90.9% and 86.4%, respectively. In contrast the cold water extract of the leaves and stem bark, each was active against 16.7%; while the ethanolic extract of each was active against 75% of the test strains. The minimum inhibitory concentrations (MIC) ranged from 7.81 mg/mL against Bacillus subtilis ATCC 6051 to 31.25 mg/mL against Escherichia coli ATCC 11775; and the minimum bactericidal concentration (MBC) ranged from 125 mg/mL against Pseudomonas aeruginosa ATCC 10145 to 250 mg/mL against Bacillus subtilis ATCC 6051. PMID- 22072894 TI - Mossbauer spectroscopy and X-ray diffraction study of Fe-labeled tetrachloroferrate(III)-based magnetic ionic liquids. AB - Four (57)Fe-labeled tetrachloroferrates(III) of organic cations (1-butyl-3 methylimidazolium, 1-allyl-3-methylimidazolium, 1-methyl-1-propylpyrrolidinium, tetraphenylphosphonium) were examined by temperature-dependent Mossbauer spectroscopy. The hyperfine and dynamic parameters of the iron(III) site were determined. Single crystal X-ray diffraction data of [Ph(4)P][FeCl(4)] were collected at four temperatures (295, 223, 173, and 123 K), and the dynamics of the iron atom inferred from the Mossbauer data and the single crystal U(i,j) parameters have been compared. PMID- 22072895 TI - Effect of Celluclast 1.5L on the physicochemical characterization of gold kiwifruit pectin. AB - The effects of Celluclast 1.5L concentration on the physicochemical characterization of gold kiwifruit pectin was evaluated. Varying the enzyme concentration affected the pectin yield and pectin physicochemical properties. The viscosity of extracted pectin was largely dependent on the enzyme concentration. Celluclast 1.5L with medium concentration exhibited the highest viscosity. Varying the enzyme concentration also influenced the molecular weight distribution. High molecular weight (M(w)) pectin (1.65 * 10(6) g/mol) was obtained when the medium concentration was used. Overall, the study clearly reflects the importance of taking into consideration the amount of cellulytic enzyme added in order to determine the final quality of pectin. PMID- 22072896 TI - Genetic variation of the Nile soft-shelled turtle (Trionyx triunguis). AB - We studied the genetic structure of Trionyx triunguis populations from the Mediterranean and African continent based on mtDNA D-loop (776 bp) and nine microsatellite loci. A total of 102 polymorphic sites and 13 mtDNA haplotypes were described. Nucleotide diversity and haplotypes diversity were 0.047 and 0.974 respectively. Both mtDNA and nDNA supported the existence of two main management units as the Mediterranean and Africa. Based on the mtDNA results, the Mediterranean can be divided into two subunits; western Turkey and the eastern Mediterranean. PMID- 22072897 TI - Antibacterial activity of new dibenzoxepinone oximes with fluorine and trifluoromethyl group substituents. AB - In this paper we present the antimicrobial activity of some newly synthesized dibenz[b,e]oxepin derivatives bearing the oximino moiety, and fluorine (F) and trifluoromethyl (CF(3)) group substituents. The chemical structure and purity of the new compounds were assessed by using elemental analysis, NMR and FTIR spectroscopy. The new compounds were screened for their antibacterial activity towards Gram-positive and Gram-negative strains, by qualitative and quantitative assays. Our results demonstrated that the CF(3) and F disubstituted compounds could be considered for the further development of novel antimicrobial drugs. PMID- 22072898 TI - A determination of potential alpha-glucosidase inhibitors from Azuki Beans (Vigna angularis). AB - A 70% ethanol extract from azuki beans (Vigna angularis) was extracted further with CH(2)Cl(2), EtOAc and n-BuOH to afford four fractions: CH(2)Cl(2)-soluble, EtOAc-soluble, n-BuOH-soluble and residual extract fractions. The EtOAc-soluble fractions showed the highest alpha-glucosidase inhibitory activity. Two pure flavonoid compounds, vitexin and isovitexin, were isolated (using the enzyme assay-guide fractionation method) from the EtOAc-soluble fractions. We further evaluated the interaction between the flavonoid compounds and alpha-glucosidase by fluorescence spectroscopy. Vitexin and isovitexin showed high inhibitory activities, with IC(50) values of 0.4 mg.mL(-1) and 4.8 mg.mL(-1), respectively. This is the first study of the active compositions of azuki beans against alpha glucosidase. PMID- 22072899 TI - Betalain, Acid ascorbic, phenolic contents and antioxidant properties of purple, red, yellow and white cactus pears. AB - Commercialization of cactus pears based on their antioxidant properties can generate competitive advantages, and these can turn into business opportunities and the development of new products and a high-value ingredient for the food industry. This work evaluated the antioxidant activities (1,1-diphenyl-2 picrylhydrazyl radical-scavenging, protection against oxidation of a beta carotene-linoleic acid emulsion, and iron (II) chelation), the content of total phenolic compounds, ascorbic acid, betacyanin, betaxanthin and the stability of betacyanin pigments in presence of Cu (II)-dependent hydroxyl radicals (OH*), in 18 cultivars of purple, red, yellow and white cactus pear from six Mexican states. Our results indicated that the antiradical activities from yellow and white cactus pear cultivars were not significantly different (p < 0.05) and were lower than the average antiradical activities in red and purple cultivars. The red cactus pear from the state of Zacatecas showed the highest antioxidant activity. The free radical scavenging activity for red cactus pears was significantly correlated (p < 0.05) to the concentration of total phenolic compounds (R(2) = 0.90) and ascorbic acid (R(2) = 0.86). All 18 cultivars of cactus pears studied showed significant chelating activity of ferrous ions. The red and purple cactus pears showed a great stability when exposed to OH*. PMID- 22072901 TI - 3D-QSAR studies on thiazolidin-4-one S1P1receptor agonists by CoMFA and CoMSIA. AB - Selective S1P(1) receptor agonists have therapeutic potential to treat a variety of immune-mediated diseases. A series of 2-imino-thiazolidin-4-one derivatives displaying potent S1P(1) receptor agonistic activity were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross validation techniques were investigated as well as some measures including region focusing, progressive scrambling, bootstraping and leave-group-out. The satisfactory CoMFA model predicted a q(2) value of 0.751 and an r(2) value of 0.973, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic, hydrophobic and H-bond donor descriptors, predicted a q(2) value of 0.739 and an r(2) value of 0.923. The models were graphically interpreted using contour plots which gave more insight into the structural requirements for increasing the activity of a compound, providing a solid basis for future rational design of more active S1P(1) receptor agonists. PMID- 22072900 TI - Metabolomics of oxidative stress in recent studies of endogenous and exogenously administered intermediate metabolites. AB - Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites-pyruvate, ethyl pyruvate, and fructose-1,6 bisphosphate-whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing "omics"-based, diagnostic tests to help influence therapies. PMID- 22072902 TI - Characterization of terpenoids from the root of Ceriops tagal with antifouling activity. AB - One new dimeric diterpenoid, 8(14)-enyl-pimar-2'(3')-en-4'(18')-en-15'(16') endolabr- 16,15,2',3'-oxoan-16-one (1) and five known terpenoids: Tagalsin C (2), Tagalsin I (3), lup-20(29)-ene-3beta,28-diol (4), 3-oxolup-20(29)-en-28-oic acid (5) and 28-hydroxylup- 20(29)-en-3-one (6) were isolated from the roots of the mangrove plant Ceriops tagal. Their structures and relative stereochemistry were elucidated by means of extensive NMR, IR and MS analysis. The antifouling activity against larval settlement of the barnacle Balanus albicostatus were evaluated using capsaicin as a positive control. All these terpenoids exhibited antifouling activity against cyprid larvae of the barnacle without significant toxicity. The structure-activity relationship results demonstrated that the order of antifouling activity was diterpenoid (Compound 2) > triterpenoid (Compounds 4, 5 and 6) > dimeric diterpenoid (Compounds 1 and 3). The functional groups on the C-28 position of lupane triterpenoid significantly affect the antifouling activity. The diterpenoid dimmer with two identical diterpenoid subunits might display more potent antifouling activity than one with two different diterpenoid subunits. The stability test showed that Compounds 2, 4, 5 and 6 remained stable over 2-month exposure under filtered seawater. PMID- 22072903 TI - Hepatoprotective and antioxidant effects of licorice extract against CCl4-induced oxidative damage in rats. AB - Licorice has been used in Chinese folk medicine for the treatment of various disorders. Licorice has the biological capabilities of detoxication, antioxidation, and antiinfection. In this study, we evaluated the antihepatotoxic effect of licorice aqueous extract (LE) on the carbon tetrachloride (CCl(4)) induced liver injury in a rat model. Hepatic damage, as reveled by histology and the increased activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and decreased levels of serum total protein (TP), albumin (Alb) and globulin (G) were induced in rats by an administration of CCl(4) at 3 mL/kg b.w. (1:1 in groundnut oil). Licorice extract significantly inhibited the elevated AST, ALP and ALT activities and the decreased TP, Alb and G levels caused by CCl(4) intoxication. It also enhanced liver super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), Glutathione S-transferase (GST) activities and glutathione (GSH) level, reduced malondialdehyde (MDA) level. Licorice extract still markedly reverses the increased liver hydroxyproline and serum TNF-alpha levels induced by CCl(4) intoxication. The data of this study support a chemopreventive potential of licorice extract against liver oxidative injury. PMID- 22072904 TI - ATP-dependent chromatin remodeling factors and their roles in affecting nucleosome fiber composition. AB - ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties. PMID- 22072906 TI - Crystallization study and comparative in vitro-in vivo hydrolysis of PLA reinforcement ligament. AB - In the present work, the crystallization behavior and in vitro-in vivo hydrolysis rates of PLA absorbable reinforcement ligaments used in orthopaedics for the repair and reinforcement of articulation instabilities were studied. Tensile strength tests showed that this reinforcement ligament has similar mechanical properties to Fascia Latta, which is an allograft sourced from the ilio-tibial band of the human body. The PLA reinforcement ligament is a semicrystalline material with a glass transition temperature around 61 degrees C and a melting point of ~178 degrees C. Dynamic crystallization revealed that, although the crystallization rates of the material are slow, they are faster than the often reported PLA crystallization rates. Mass loss and molecular weight reduction measurements showed that in vitro hydrolysis at 50 degrees C initially takes place at a slow rate, which gets progressively higher after 30-40 days. As found from SEM micrographs, deterioration of the PLA fibers begins during this time. Furthermore, as found from in vivo hydrolysis in the human body, the PLA reinforcement ligament is fully biocompatible and after 6 months of implantation is completely covered with flesh. However, the observed hydrolysis rate from in vivo studies was slow due to high molecular weight and degree of crystallinity. PMID- 22072905 TI - The potential of antimicrobial peptides as biocides. AB - Antimicrobial peptides constitute a diverse class of naturally occurring antimicrobial molecules which have activity against a wide range of pathogenic microorganisms. Antimicrobial peptides are exciting leads in the development of novel biocidal agents at a time when classical antibiotics are under intense pressure from emerging resistance, and the global industry in antibiotic research and development stagnates. This review will examine the potential of antimicrobial peptides, both natural and synthetic, as novel biocidal agents in the battle against multi-drug resistant pathogen infections. PMID- 22072907 TI - Modulation of human serotonin transporter expression by 5-HTTLPR in colon cells. AB - Serotonin (5-HT) is a monoamine neurotransmitter and plays important roles in several of the human body's systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT) plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR). It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR), lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L) allele as compared to short (S) allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05) as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5 HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells. PMID- 22072908 TI - Quantitative comparative analysis of the bio-active and toxic constituents of leaves and spikes of Schizonepeta tenuifolia at different harvesting times. AB - A GC-MS-Selected Ion Monitoring (SIM) detection method was developed for simultaneous determination of four monoterpenes: (-)-menthone, (+)-pulegone, (-) limonene and (+)-menthofuran as the main bio-active and toxic constituents, and four other main compounds in the volatile oils of Schizonepeta tenuifolia (ST) leaves and spikes at different harvesting times. The results showed that the method was simple, sensitive and reproducible, and that harvesting time was a possible key factor in influencing the quality of ST leaves, but not its spikes. The research might be helpful for determining the harvesting time of ST samples and establishing a validated method for the quality control of ST volatile oil and other relative products. PMID- 22072909 TI - Expression of elongation factor (EF)-Tu is correlated with prognosis of gastric adenocarcinomas. AB - Altered expressions of mitochondria elongation factor Tu (EF-Tu) have been observed in certain types of cancers, including gastric cancer cell lines, but the impact of the alterations in gastric adenocarcinoma remains unclear. The purpose of this study was to investigate the expression of EF-Tu in gastric adenocarcinoma and to assess its clinical significance. A total of 104 paired resected gastric adenocarcinoma and corresponding normal specimens were collected in this study. EF-Tu expression was assessed by immunohistochemical staining. The correlation of EF-Tu expression and patients' clinicopathological parameters was statically evaluated and the prognostic significance of EF-Tu expression was assessed by univariate and multivariate analyses. Forty-nine out of 104 (47.1%) gastric adenocarcinoma specimens showed high expression of EF-Tu, while the remaining 55 specimens showed weak or negative expression of EF-Tu. In contrast, EF-Tu high expression was detected in 62.5% (65 of 104) normal tissues. Down regulation of EF-Tu was associated with serosal invasion (P = 0.042) and node involvement (P = 0.005), and down-regulation of EF-Tu was correlated with poor overall survival (P = 0.020). In curative resection (R0) patients, there were also significant differences (P = 0.043). In the multivariate analysis, the EF-Tu expression remained a significant independent prognostic factor (P = 0.038). Our results indicate that EF-Tu is expressed in both gastric adenocarcinoma and corresponding normal tissues. Down-regulation of EF-Tu expression is associated with advanced disease stage and EF-Tu expression maybe served as an independent prognostic factor. PMID- 22072910 TI - Molecular quantum spintronics: supramolecular spin valves based on single molecule magnets and carbon nanotubes. AB - We built new hybrid devices consisting of chemical vapor deposition (CVD) grown carbon nanotube (CNT) transistors, decorated with TbPc(2) (Pc = phthalocyanine) rare-earth based single-molecule magnets (SMMs). The drafting was achieved by tailoring supramolecular pi-pi interactions between CNTs and SMMs. The magnetoresistance hysteresis loop measurements revealed steep steps, which we can relate to the magnetization reversal of individual SMMs. Indeed, we established that the electronic transport properties of these devices depend strongly on the relative magnetization orientations of the grafted SMMs. The SMMs are playing the role of localized spin polarizer and analyzer on the CNT electronic conducting channel. As a result, we measured magneto-resistance ratios up to several hundred percent. We used this spin valve effect to confirm the strong uniaxial anisotropy and the superparamagnetic blocking temperature (T(B) ~ 1 K) of isolated TbPc(2) SMMs. For the first time, the strength of exchange interaction between the different SMMs of the molecular spin valve geometry could be determined. Our results introduce a new design for operable molecular spintronic devices using the quantum effects of individual SMMs. PMID- 22072911 TI - Principal component analysis coupled with artificial neural networks--a combined technique classifying small molecular structures using a concatenated spectral database. AB - In this paper we present several expert systems that predict the class identity of the modeled compounds, based on a preprocessed spectral database. The expert systems were built using Artificial Neural Networks (ANN) and are designed to predict if an unknown compound has the toxicological activity of amphetamines (stimulant and hallucinogen), or whether it is a nonamphetamine. In attempts to circumvent the laws controlling drugs of abuse, new chemical structures are very frequently introduced on the black market. They are obtained by slightly modifying the controlled molecular structures by adding or changing substituents at various positions on the banned molecules. As a result, no substance similar to those forming a prohibited class may be used nowadays, even if it has not been specifically listed. Therefore, reliable, fast and accessible systems capable of modeling and then identifying similarities at molecular level, are highly needed for epidemiological, clinical, and forensic purposes. In order to obtain the expert systems, we have preprocessed a concatenated spectral database, representing the GC-FTIR (gas chromatography-Fourier transform infrared spectrometry) and GC-MS (gas chromatography-mass spectrometry) spectra of 103 forensic compounds. The database was used as input for a Principal Component Analysis (PCA). The scores of the forensic compounds on the main principal components (PCs) were then used as inputs for the ANN systems. We have built eight PC-ANN systems (principal component analysis coupled with artificial neural network) with a different number of input variables: 15 PCs, 16 PCs, 17 PCs, 18 PCs, 19 PCs, 20 PCs, 21 PCs and 22 PCs. The best expert system was found to be the ANN network built with 18 PCs, which accounts for an explained variance of 77%. This expert system has the best sensitivity (a rate of classification C = 100% and a rate of true positives TP = 100%), as well as a good selectivity (a rate of true negatives TN = 92.77%). A comparative analysis of the validation results of all expert systems is presented, and the input variables with the highest discrimination power are discussed. PMID- 22072912 TI - Effect of peptide size on antioxidant properties of African yam bean seed (Sphenostylis stenocarpa) protein hydrolysate fractions. AB - Enzymatic hydrolysate of African yam bean seed protein isolate was prepared by treatment with alcalase. The hydrolysate was further fractionated into peptide sizes of <1, 1-3, 3-5 and 5-10 kDa using membrane ultrafiltration. The protein hydrolysate (APH) and its membrane ultrafiltration fractions were assayed for in vitro antioxidant activities. The <1 kDa peptides exhibited significantly better (p < 0.05) ferric reducing power, diphenyl-1-picryhydradzyl (DPPH) and hydroxyl radical scavenging activities when compared to peptide fractions of higher molecular weights. The high activity of <1 kDa peptides in these antioxidant assay systems may be related to the high levels of total hydrophobic and aromatic amino acids. In comparison to glutathione (GSH), the APH and its membrane fractions had significantly higher (p < 0.05) ability to chelate metal ions. In contrast, GSH had significantly greater (p < 0.05) ferric reducing power and free radical scavenging activities than APH and its membrane fractions. The APH and its membrane fractions effectively inhibited lipid peroxidation, results that were concentration dependent. The activity of APH and its membrane fractions against linoleic acid oxidation was higher when compared to that of GSH but lower than that of butylated hydroxyl toluene (BHT). The results show potential use of APH and its membrane fractions as antioxidants in the management of oxidative stress-related metabolic disorders and in the prevention of lipid oxidation in food products. PMID- 22072913 TI - Comparative kinetic study and microwaves non-thermal effects on the formation of poly(amic acid) 4,4'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and 4,4'-(hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline (BAPHF). Reaction activated by microwave, ultrasound and conventional heating. AB - Green chemistry is the design of chemical processes that reduce or eliminate negative environmental impacts. The use and production of chemicals involve the reduction of waste products, non-toxic components, and improved efficiency. Green chemistry applies innovative scientific solutions in the use of new reagents, catalysts and non-classical modes of activation such as ultrasounds or microwaves. Kinetic behavior and non-thermal effect of poly(amic acid) synthesized from (6FDA) dianhydride and (BAPHF) diamine in a low microwave absorbing p-dioxane solvent at low temperature of 30, 50, 70 degrees C were studied, under conventional heating (CH), microwave (MW) and ultrasound irradiation (US). Results show that the polycondensation rate decreases (MW > US > CH) and that the increased rates observed with US and MW are due to decreased activation energies of the Arrhenius equation. Rate constant for a chemical process activated by conventional heating declines proportionally as the induction time increases, however, this behavior is not observed under microwave and ultrasound activation. We can say that in addition to the thermal microwave effect, a non-thermal microwave effect is present in the system. PMID- 22072914 TI - Molecular identification of Fusarium species in Gibberella fujikuroi species complex from rice, sugarcane and maize from Peninsular Malaysia. AB - The objective of this study was to identify Fusarium species in the Gibberella fujikuroi species complex from rice, sugarcane and maize as most of the Fusarium species in the species complex are found on the three crops. Isolates used were collected from the field and obtained from culture collection. The Fusarium isolates were initially sorted based on morphology and identifications confirmed based on the DNA sequence of the translation elongation factor 1-alpha (TEF 1alpha) gene. Based on the closest match of BLAST analysis, five species were recovered, namely, F. sacchari, F. fujikuroi, F. proliferatum, F. andiyazi and F. verticillioides. This is the first report regarding F. andiyazi from rice in Malaysia and Southeast Asia. The phylogenetic tree generated by using the neighbor joining method showed that isolates from the same species were grouped in the same clade. The present study indicated that Fusarium species in the G. fujikuroi species complex are widespread in rice, sugarcane and maize in Peninsular Malaysia. The findings also suggest that the use of morphological characters for identification of Fusarium species in the G. fujikuroi species complex from the three crops will lead to incorrect species designation. PMID- 22072916 TI - A set of novel microsatellite markers developed for a distylous species Luculia gratissima (Rubiaceae). AB - Luculia gratissima (Wall.) Sweet (Rubiaceae) is a perennial shrub distributed in the southeast margin of the Tibetan Plateau in southwest China and adjacent region of Nepal and Myanmar. The plant is a distylous species with reciprocally placed stigmas and anthers in each floral morph. By using the Fast Isolation by Amplified Fragment Length Polymorphism (AFLP) of Sequences Containing (FIASCO) repeats protocol, 19 primer sets were identified in two wild populations. Of these primers, 10 displayed polymorphisms and nine were monomorphic. The number of alleles per locus ranged from two to five, values for observed and expected heterozygosities ranged from 0.000 to 1.000 and from 0.289 to 0.760, with averages of 0.303 and 0.555, respectively. These microsatellite loci will facilitate further studies on breeding system, gene flow patterns, and population structure of L. gratissima and its allied species. PMID- 22072915 TI - The role of microRNAs in the biology of rare diseases. AB - Rare diseases (RD) are characterized by low prevalence and affect not more than five individuals per 10,000 in the European population; they are a large and heterogeneous group of disorders including more than 7,000 conditions and often involve all organs and tissues, with several clinical subtypes within the same disease. Very often information concerning either diagnosis and/or prognosis on many RD is insufficient. microRNAs are a class of small non-coding RNAs that regulate gene expression at the posttranscriptional level by either degrading or blocking translation of messenger RNA targets. Recently, microRNA expression patterns of body fluids underscored their potential as noninvasive biomarkers for various diseases. The role of microRNAs as potential biomarkers has become particularly attractive. The identification of disease-related microRNAs is essential for understanding the pathogenesis of diseases at the molecular level, and is critical for designing specific molecular tools for diagnosis, treatment and prevention. Computational analysis of microRNA-disease associations is an important complementary means for prioritizing microRNAs for further experimental examination. In this article, we explored the added value of miRs as biomarkers in a selected panel of RD hitting different tissues/systems at different life stages, but sharing the need of better biomarkers for diagnostic and prognostic purposes. PMID- 22072917 TI - Hyaluronan and fibrin biomaterial as scaffolds for neuronal differentiation of adult stem cells derived from adipose tissue and skin. AB - Recently, we have described a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. Due to their possible application in neuronal tissue regeneration, here we tested two kinds of scaffold well known in tissue engineering application: hyaluronan based membranes and fibrin-glue meshes. Neurospheres from skin and adipose tissue were seeded onto two scaffold types: hyaluronan based membrane and fibrin-glue meshes. Neurospheres were then induced to acquire a glial and neuronal-like phenotype. Gene expression, morphological feature and chromosomal imbalance (kariotype) were analyzed and compared. Adipose and skin derived neurospheres are able to grow well and to differentiate into glial/neuron cells without any chromosomal imbalance in both scaffolds. Adult cells are able to express typical cell surface markers such as S100; GFAP; nestin; betaIII tubulin; CNPase. In summary, we have demonstrated that neurospheres isolated from skin and adipose tissues are able to differentiate in glial/neuron-like cells, without any chromosomal imbalance in two scaffold types, useful for tissue engineering application: hyaluronan based membrane and fibrin glue meshes. PMID- 22072918 TI - A novel cold-adapted lipase from Sorangium cellulosum strain So0157-2: gene cloning, expression, and enzymatic characterization. AB - Genome sequencing of cellulolytic myxobacterium Sorangium cellulosum reveals many open-reading frames (ORFs) encoding various degradation enzymes with low sequence similarity to those reported, but none of them has been characterized. In this paper, a predicted lipase gene (lipA) was cloned from S. cellulosum strain So0157 2 and characterized. lipA is 981-bp in size, encoding a polypeptide of 326 amino acids that contains the pentapeptide (GHSMG) and catalytic triad residues (Ser114, Asp250 and His284). Searching in the GenBank database shows that the LipA protein has only the 30% maximal identity to a human monoglyceride lipase. The novel lipA gene was expressed in Escherichia coli BL21 and the recombinant protein (r-LipA) was purified using Ni-NTA affinity chromatography. The enzyme hydrolyzed the p-nitrophenyl (pNP) esters of short or medium chain fatty acids (<=C(10)), and the maximal activity was on pNP acetate. The r- LipA is a cold adapted lipase, with high enzymatic activity in a wide range of temperature and pH values. At 4 degrees C and 30 degrees C, the K(m) values of r-LipA on pNP acetate are 0.037 +/- 0.001 and 0.174 +/- 0.006 mM, respectively. Higher pH and temperature conditions promoted hydrolytic activity toward the pNP esters with longer chain fatty acids. Remarkably, this lipase retained much of its activity in the presence of commercial detergents and organic solvents. The results suggest that the r-LipA protein has some new characteristics potentially promising for industrial applications and S. cellulosum is an intriguing resource for lipase screening. PMID- 22072919 TI - The stimulation of IGF-1R expression by Lewis(y) antigen provides a powerful development mechanism of epithelial ovarian carcinoma. AB - OBJECTIVE: This study aimed to measure and correlate the expression of insulin like growth factor receptor-1 (IGF-1R) and the Lewis(y) antigen in ovarian cancer cell lines and tissue samples. METHODS: Reverse transcriptase PCR (RT-PCR), Western blotting, immunoprecipitation, immunohistochemistry, and immunofluorescence double-labeling techniques were applied to detect and measure the expression of Lewis(y) and IGF-1R. RESULTS: In alpha1,2-fucosyltransferase (alpha1,2-FT)-transfected cells, IGF-1R expression was significantly upregulated compared with cells that do not overexpress alpha1,2-FT (P < 0.05). The amount of Lewis(y) expressed on IGF-1R increased 1.81-fold in alpha1,2-FT-overexpressing cells (P < 0.05), but the ratio of Lewis(y) expressed on IGF-1R to total IGF-1R was unaltered between two cells (P > 0.05). In malignant epithelial ovarian tumors, the positivity rates of Lewis(y) and IGF-1R detection were 88.3% and 93.33%, respectively, which is higher than the positivity rates in marginal (60.00% and 63.33%, all P < 0.05), benign (33.00% and 53.33%, all P < 0.01), and normal (0% and 40%, all P < 0.01) ovarian samples. No correlations were detected in positivity rates of Lewis(y) or IGF-1R expression with respect to clinicopathological parameters in ovarian cancers (all P > 0.05). Both IGF-1R and Lewis(y) were highly expressed in ovarian cancer tissues, and their expression levels were positively correlated (P < 0.05). CONCLUSION: Overexpression of Lewis(y) results in overexpression of IGF-1R. Both IGF-1R and Lewis(y) are associated with the occurrence and development of ovarian cancers. PMID- 22072920 TI - Nuclear markers of Danube Sturgeons hybridization. AB - Acipenseriformes are composed of 25 sturgeon species and two paddlefish species distributed exclusively in the northern hemisphere. The Danube River and the Black Sea were originally inhabited by six sturgeon species but two are extinct and only four are still reproducing currently in the Lower Danube: Huso huso, Acipenser stellatus, A. gueldenstaedtii and A. ruthenus. Sturgeon species hybridize more easily than other fish and the determination of pure species or hybrid status is important for conservation and for breeding in fish farms. This survey demonstrated that morphological determination of this status is not reliable and a molecular tool, based on eight microsatellites genotypes is proposed. This method, based on three successive statistical analyses including Factorial Correspondence Analysis (FCA), Structure assignation and NewHybrids status determination, showed a high efficiency in discriminating pure species specimens from F1, F2 and two kinds of backcross individuals involving three of the four reproducing Lower Danube sturgeon species. PMID- 22072921 TI - Far from equilibrium percolation, stochastic and shape resonances in the physics of life. AB - Key physical concepts, relevant for the cross-fertilization between condensed matter physics and the physics of life seen as a collective phenomenon in a system out-of-equilibrium, are discussed. The onset of life can be driven by: (a) the critical fluctuations at the protonic percolation threshold in membrane transport; (b) the stochastic resonance in biological systems, a mechanism that can exploit external and self-generated noise in order to gain efficiency in signal processing; and (c) the shape resonance (or Fano resonance or Feshbach resonance) in the association and dissociation processes of bio-molecules (a quantum mechanism that could play a key role to establish a macroscopic quantum coherence in the cell). PMID- 22072922 TI - Nuclei of Tsuga canadensis: role of flavanols in chromatin organization. AB - Needle primordia of Tsuga canadensis (hemlock) arising from flank meristems of a shoot apex, form cell lineages consisting of four or eight cells. Within a recently established lineage there is striking uniformity in the pattern of nuclear flavanols. This fact points to an identical transcriptional expression of these flavanols during cell cycling. However two lineages, even if located close together within the same meristem, can be very different in the expression of both cell shape and nuclear flavanol pattern, indicating that epigenetic positional signals are operating in a collective specification of cell lineage development. There is a wide range of nuclear flavanol patterning from a mosaic like distribution in an activated cell type to a homogenous appearance in silenced cell types. Single cells deriving from lineages are desynchronized because they underlie a signaling network at a higher tissue level which results in stronger epigenetic modifications of their nuclear flavanols. As an extreme case of epigenetic modulation, transient drought conditions caused a drastic reduction of nuclear flavanols. Upon treatment with sucrose or cytokinin, these nuclear flavanols could be fully restored. Analytical determination of the flavanols revealed 3.4 mg/g DW for newly sprouting needles and 19.6 mg/g DW for anthers during meiosis. The roughly 6-fold difference in flavanols is apparently a reflection of the highly diverging organogenetic processes. Collectively, the studies provide strong evidence for combinatorial interplay between cell fate and nuclear flavanols. PMID- 22072923 TI - Supercritical carbon dioxide extraction of bioactive compounds from Ampelopsis grossedentata stems: process optimization and antioxidant activity. AB - Supercritical carbon dioxide (SC-CO(2)) extraction of bioactive compounds including flavonoids and phenolics from Ampelopsis grossedentata stems was carried out. Extraction parameters such as pressure, temperature, dynamic time and modifier, were optimized using an orthogonal array design of L(9) (3(4)), and antioxidant activities of the extracts were evaluated by 2,2-diphenyl-1 picrylhydrazyl (DPPH) free radical scavenging assay and ferrous ion chelating (FIC) assay. The best conditions obtained for SC-CO(2) extraction of flavonoids was 250 bar, 40 degrees C, 50 min, and with a modifier of methanol/ethanol (1:3, v/v), and that for phenolics extraction was 250 bar, 40 degrees C, 50 min, and with a modifier of methanol/ethanol (1:1, v/v). Meantime, flavonoids and phenolics were found to be mainly responsible for the DPPH scavenging activity of the extracts, but not for the chelating activity on ferrous ion according to Pearson correlation analysis. Furthermore, several unreported flavonoids such as apigenin, vitexin, luteolin, etc., have been detected in the extracts from A. grossedentata stems. PMID- 22072924 TI - Assessing molecular signature for some potential date (Phoenix dactylifera L.) cultivars from Saudi Arabia, based on chloroplast DNA sequences rpoB and psbA trnH. AB - Phoenix dactylifera L. (date palm), being economically very important, is widely cultivated in the Middle East and North Africa, having about 400 different cultivars. Assessment of date cultivars under trading and farming is a widely accepted problem owing to lack of a unique molecular signature for specific date cultivars. In the present study, eight different cultivars of dates viz., Khodry, Khalas, Ruthana, Sukkari, Sefri, Segae, Ajwa and Hilali were sequenced for rpoB and psbA-trnH genes and analyzed using bioinformatics tools to establish a cultivar-specific molecular signature. The combined aligned data matrix was of 1147 characters, of which invariable and variable sites were found to be 958 and 173, respectively. The analysis clearly reveals three major groups of these cultivars: (i) Khodary, Sefri, Ajwa, Ruthana and Hilali (58% BS); (ii) Sukkari and Khalas (64% BS); and (iii) Segae. The economically most important cultivar Ajwa showed similarity with Khodary and Sefri (67% BS).The sequences of the date cultivars generated in the present study showed bootstrap values between 38% and 70% so these sequences could be carefully used as molecular signature for potential date cultivars under trading and selection of genuine cultivars at the seedling stage for farming. PMID- 22072927 TI - Evaluation of antioxidant compounds and total sugar content in a nectarine [Prunus persica (L.) Batsch] progeny. AB - Epidemiological studies suggest that consumption of fruit rich in phenolic compounds is associated with health-protective effects due to their antioxidant properties. For these reasons quality evaluation has become an important issue in fruit industry and in breeding programs. Phytochemical traits such as total phenolics, flavonoids, anthocyanins, L-ascorbic acid, sugar content and relative antioxidant capacity (RAC) were analyzed over four years in flesh fruit of an F1 population "Venus" * "Big Top" nectarines. Other traits such as harvesting date, yield, fruit weight, firmness, soluble solids concentration (SSC), pH, titratable acidity (TA) and ripening index (RI) were also determined in the progeny. Results showed high variability among genotypes for all analyzed traits. Total phenolics and flavonoids showed significant positive correlations with RAC implying that both are important antioxidant bioactive compounds in peaches. We found genotypes with enhanced antioxidant capacity and a better performance than progenitors, and in consequence the best marketability. PMID- 22072926 TI - Metal-induced oxidative stress and plant mitochondria. AB - A general status of oxidative stress in plants caused by exposure to elevated metal concentrations in the environment coincides with a constraint on mitochondrial electron transport, which enhances ROS accumulation at the mitochondrial level. As mitochondria are suggested to be involved in redox signaling under environmental stress conditions, mitochondrial ROS can initiate a signaling cascade mediating the overall stress response, i.e., damage versus adaptation. This review highlights our current understanding of metal-induced responses in plants, with focus on the production and detoxification of mitochondrial ROS. In addition, the potential involvement of retrograde signaling in these processes will be discussed. PMID- 22072925 TI - Malignant catarrhal fever: understanding molecular diagnostics in context of epidemiology. AB - Malignant catarrhal fever (MCF) is a frequently fatal disease, primarily of ruminants, caused by a group of gammaherpesviruses. Due to complexities of pathogenesis and epidemiology in various species, which are either clinically susceptible or reservoir hosts, veterinary clinicians face significant challenges in laboratory diagnostics. The recent development of specific assays for viral DNA and antibodies has expanded and improved the inventory of laboratory tests and opened new opportunities for use of MCF diagnostics. Issues related to understanding and implementing appropriate assays for specific diagnostic needs must be addressed in order to take advantage of molecular diagnostics in the laboratory. PMID- 22072928 TI - N-acetylcysteine reduces markers of differentiation in 3T3-L1 adipocytes. AB - Oxidative stress plays a critical role in the pathogenesis of diabetes, hypertension and atherosclerosis. Some authors reported that fat accumulation correlates to systemic oxidative stress in humans and mice, but the relationship of lipid production and oxidative metabolism is still unclear. In our laboratory we used 3T3-L1 preadipocytes, which are able to differentiate into mature adipocytes and accumulate lipids, as obesity model. We showed that intracellular reactive oxygen species (ROS) and antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased in parallel with fat accumulation. Meanwhile N-acetylcysteine (NAC), a well known antioxidant and Glutathione (GSH) precursor, inhibited ROS levels as well as fat accumulation in a concentration-dependent manner. NAC also inhibited both adipogenic transcription factors CCAAT/enhancer binding protein beta (C/EBP beta) and peroxisomal proliferator activated receptor gamma (PPAR gamma) expression; we suggested that intracellular GSH content could be responsible for these effects. PMID- 22072929 TI - In vitro anti-listerial activities of crude n-hexane and aqueous extracts of Garcinia kola (heckel) seeds. AB - We assessed the anti-Listerial activities of crude n-hexane and aqueous extracts of Garcinia kola seeds against a panel of 42 Listeria isolates previously isolated from wastewater effluents in the Eastern Cape Province of South Africa and belonging to Listeria monocytogenes, Listeria grayi and Listeria ivanovii species. The n-hexane fraction was active against 45% of the test bacteria with zones of inhibition ranging between 8-17 mm, while the aqueous fraction was active against 29% with zones of inhibition ranging between 8-11 mm. The minimum inhibitory concentrations (MIC) were within the ranges of 0.079-0.625 mg/mL for the n-hexane extract and 10 to >10 mg/mL for the aqueous extract. The rate of kill experiment carried out for the n-hexane extract only, revealed complete elimination of the initial bacterial population for L. grayi (LAL 15) at 3* and 4* MIC after 90 and 60 min; L. monocytogenes (LAL 8) at 3* and 4* MIC after 60 and 15 min; L. ivanovii (LEL 18) at 3* and 4* MIC after 120 and 15 min; L. ivanovii (LEL 30) at 2, 3 and 4* MIC values after 105, 90 and 15 min exposure time respectively. The rate of kill activities were time- and concentration dependant and the extract proved to be bactericidal as it achieved a more than 3log(10) decrease in viable cell counts after 2 h exposure time for all of the four test organisms at 3* and 4* MIC values. The results therefore show the potential presence of anti-Listerial compounds in Garcinia kola seeds that can be exploited in effective anti-Listerial chemotherapy. PMID- 22072930 TI - Environmental dependence of artifact CD peaks of chiral Schiff base 3d-4f complexes in soft mater PMMA matrix. AB - Four chiral Schiff base binuclear 3d-4f complexes (NdNi, NdCu, GdNi, and GdCu) have been prepared and characterized by means of electronic and CD spectra, IR spectra, magnetic measurements, and X-ray crystallography (NdNi). A so-called artifact peak of solid state CD spectra, which was characteristic of oriented molecules without free molecular rotation, appeared at about 470 nm. Magnetic data of the complexes in the solid state (powder) and in PMMA cast films or solutions indicated that only GdCu preserved molecular structures in various matrixes of soft maters. For the first time, we have used the changes of intensity of artifact CD peaks to detect properties of environmental (media solid state (KBr pellets), PMMA cast films, concentration dependence of PMMA in acetone solutions, and pure acetone solution) for chiral 3d-4f complexes (GdCu). Rigid matrix keeping anisotropic orientation exhibited a decrease in the intensity of the artifact CD peak toward negative values. The present results suggest that solid state artifact CD peaks can be affected by environmental viscosity of a soft mater matrix. PMID- 22072932 TI - Structural determinants of CX-4945 derivatives as protein kinase CK2 inhibitors: a computational study. AB - Protein kinase CK2, also known as casein kinase-2, is involved in a broad range of physiological events including cell growth, proliferation and suppression of apoptosis which are related to human cancers. A series of compounds were identified as CK2 inhibitors and their inhibitory activities varied depending on their structures. In order to explore the structure-activity correlation of CX 4945 derivatives as inhibitors of CK2, in the present study, a set of ligand- and receptor-based 3D-QSAR models were developed employing Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA). The optimum CoMFA (R(cv) (2) = 0.618, R(pred) (2) = 0.892) and CoMSIA (R(cv) (2) = 0.681, R(pred) (2) = 0.843) models exhibited reasonable statistical characteristics for CX-4945 derivatives. The results indicated that electrostatic effects contributed the most to both CoMFA and CoMSIA models. The combination of docking analysis and molecular dynamics (MD) simulation showed that Leu45, Lys68, Glu81, Val116, Asp175 and Trp176 of CK2 which formed several direct or water bridged H-bonds with CX-4945 are crucial for CX-4945 derivatives recognition to CK2. These results can offer useful theoretical references for designing more potent CK2 inhibitors. PMID- 22072933 TI - Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies on alpha(1A)-adrenergic receptor antagonists based on pharmacophore molecular alignment. AB - The alpha(1A)-adrenergic receptor (alpha(1A)-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D QSAR) studies were performed on a set of alpha(1A)-AR antagonists of N-aryl and N nitrogen class. Statistically significant models constructed from comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established based on a training set of 32 ligands using pharmacophore-based molecular alignment. The leave-oneout cross-validation correlation coefficients were q(2) (CoMFA) = 0.840 and q(2) (CoMSIA) = 0.840. The high correlation between the cross-validated/predicted and experimental activities of a test set of 12 ligands revealed that the CoMFA and CoMSIA models were robust (r(2) (pred) (/CoMFA) = 0.694; r(2) (pred) (/CoMSIA) = 0.671). The generated models suggested that electrostatic, hydrophobic, and hydrogen bonding interactions play important roles between ligands and receptors in the active site. Our study serves as a guide for further experimental investigations on the synthesis of new compounds. Structural modifications based on the present 3D-QSAR results may lead to the discovery of other alpha(1A)-AR antagonists. PMID- 22072931 TI - Protein misdirection inside and outside motor neurons in Amyotrophic Lateral Sclerosis (ALS): a possible clue for therapeutic strategies. AB - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive muscle wasting and weakness with no effective cure. Emerging evidence supports the notion that the abnormal conformations of ALS linked proteins play a central role in triggering the motor neuron degeneration. In particular, mutant types of superoxide dismutase 1 (SOD1) and TAR DNA binding protein 43kDa (TDP-43) are key molecules involved in the pathogenesis of familial and sporadic ALS, respectively. The commonalities of the two proteins include a propensity to aggregate and acquire detrimental conformations through oligomerization, fragmentation, or post-translational modification that may drive abnormal subcellular localizations. Although SOD1 is a major cytosolic protein, mutated SOD1 has been localized to mitochondria, endoplasmic reticulum, and even the extracellular space. The nuclear exclusion of TDP-43 is a pathological hallmark for ALS, although the pathogenic priority remains elusive. Nevertheless, these abnormal behaviors based on the protein misfolding are believed to induce diverse intracellular and extracellular events that may be tightly linked to non cell-autonomous motor neuron death. The generation of mutant- or misfolded protein-specific antibodies would help to uncover the distribution and propagation of the ALS-linked proteins, and to design a therapeutic strategy to clear such species. Herein we review the literature regarding the mislocalization of ALS-linked proteins, especially mutant SOD1 and TDP-43 species, and discuss the rationale of molecular targeting strategies including immunotherapy. PMID- 22072934 TI - Candida colonization index in patients admitted to an ICU. AB - Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI >= 0.5. Three patients developed candidemia; they had CI >= 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients. PMID- 22072935 TI - Biological potential of sixteen legumes in China. AB - Phenolic acids have been identified in a variety of legumes including lima bean, broad bean, common bean, pea, jack bean, goa bean, adzuki bean, hyacinth bean, chicking vetch, garbanzo bean, dral, cow bean, rice bean, mung bean and soybean. The present study was carried out with the following aims: (1) to identify and quantify the individual phenolic acid and determine the total phenolic content (TPC); (2) to assess their antioxidant activity, inhibition activities of alpha glucosidase, tyrosinase, and formation of advanced glycation endproducts; and (3) to investigate correlations among the phytochemicals and biological activity. Common bean possesses the highest antioxidant activity and advanced glycation endproducts formation inhibition activity. Adzuki bean has the highest alpha glucosidase inhibition activity, and mung bean has the highest tyrosinase inhibition activity. There are significant differences in phytochemical content and functional activities among the bean species investigated. Selecting beans can help treat diseases such as dermatological hyperpigmentation illness, type 2 diabetes and associated cardiovascular diseases. PMID- 22072936 TI - Anti-UVC irradiation and metal chelation properties of 6-benzoyl-5,7-dihydroxy-4 phenyl-chromen-2-one: an implications for anti-cataract agent. AB - Coumarin derivative 1, 5,7-dihydroxy-6-(3-methyl-1-butyryl)-4-phenyl-chromen- 2 one, has been reported to possess radical scavenging activity and DNA protection. We have synthesized a series of coumarins with structural modifications at positions C4, C5, C6 and C7 and evaluated them for their anti-UVC properties. Coumarin 7, 6-benzoyl-5,6-dihydroxy-4-phenyl-chromen-2-one, was found to have the most potent activity in protecting porcine gamma-crystallin against UVC insults. Results of fluorescence assays indicated that compound 7 was capable of decreasing the loss of intensity while lens crystallins and DNA PUC19 were irradiated with UVC. Presence of compound 7 decreased hydroxyl radical levels determined by probe 1b and the free iron concentrations determined by Ferrozine reagent. The chelation assay showed that compound 7 was chelated to metal via 6 CO and 5-OH on the benzopyrone ring. The observed protective effects of compound 7 towards crystallins from insults of UVC and free radicals may be due to its iron-chelating activity and its peak absorption at 254 nm. PMID- 22072937 TI - Biomarkers in tumor angiogenesis and anti-angiogenic therapy. AB - Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti angiogenic cytokines. Among them VEGF (vascular endothelial growth factor) and its signaling through its receptors are of crucial relevance. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities and multiple new drugs are being tested in clinical trials. However not all patients are likely to respond to these therapies, but to date there are no reliable biomarkers available to predict therapy response. Many studies integrated biomarker programs in their study protocols, thus several potential biomarkers have been identified which are currently under clinical investigation in prospective randomized studies. This review intends to give an overview of the described potential biomarkers as well as different imaging techniques such as ultrasound and magnetic resonance imaging that can indicate benefit, resistance and toxicity to anti-angiogenic therapies. PMID- 22072938 TI - Cardioprotective effects of glycyrrhizic acid against isoproterenol-induced myocardial ischemia in rats. AB - The aim of the present study was to look into the possible protective effects of glycyrrhizic acid (GA) against isoproterenol-induced acute myocardial infarction in Sprague-Dawley rats. The effect of three doses of glycyrrhizic acid in response to isoproterenol (ISO)-induced changes in 8-isoprostane, lipid hydroperoxides, super oxide dismutase and total glutathione were evaluated. Male Sprague-Dawley rats were divided into control, ISO-control, glycyrrhizic acid alone (in three doses-5, 10 and 20 mg/kg BW) and ISO with glycyrrhizic acid (in three doses) groups. ISO was administered at 85 mg/kg BW at two consecutive days and glycyrrhizic acid was administered intraperitoneally for 14 days. There was a significant increase in 8-isoprostane (IP) and lipid hydroperoxide (LPO) level in ISO-control group. A significant decrease in total superoxide dismutase (SOD) and total glutathione (GSH) was seen with ISO-induced acute myocardial infarction. Treatment with GA significantly increased SOD and GSH levels and decreased myocardial LPO and IP levels. Histopathologically, severe myocardial necrosis and nuclear pyknosis and hypertrophy were seen in ISO-control group, which was significantly reduced with GA treatment. Gycyrrhizic acid treatment proved to be effective against isoproterenol-induced acute myocardial infarction in rats and GA acts as a powerful antioxidant and reduces the myocardial lipid hydroperoxide and 8-isoprostane level. PMID- 22072941 TI - Metal complexes of diisopropylthiourea: synthesis, characterization and antibacterial studies. AB - Co(II), Cu(II), Zn(II) and Fe(III) complexes of diisopropylthiourea have been synthesized and characterized by elemental analyses, molar conductivity, magnetic susceptibility, FTIR and electronic spectroscopy. The compounds are non electrolytes in solution and spectroscopic data of the complexes are consistent with 4-coordinate geometry for the metal(II) complexes and six coordinate octahedral for Fe(III) complex. The complexes were screened for their antibacterial activities against six bacteria: Escherichia coli, Pseudomonas auriginosa, Klebsiella pneumoniae, Bacillus cereus, Staphylococcus aureus and Bacillus pumilus. The complexes showed varied antibacterial activities and their minimum inhibitory concentrations (MICs) were determined. PMID- 22072940 TI - Mitochondrial peroxiredoxin III is a potential target for cancer therapy. AB - Mitochondria are involved either directly or indirectly in oncogenesis and the alteration of metabolism in cancer cells. Cancer cells contain large numbers of abnormal mitochondria and produce large amounts of reactive oxygen species (ROS). Oxidative stress is caused by an imbalance between the production of ROS and the antioxidant capacity of the cell. Several cancer therapies, such as chemotherapeutic drugs and radiation, disrupt mitochondrial homeostasis and release cytochrome c, leading to apoptosome formation, which activates the intrinsic pathway. This is modulated by the extent of mitochondrial oxidative stress. The peroxiredoxin (Prx) system is a cellular defense system against oxidative stress, and mitochondria in cancer cells are known to contain high levels of Prx III. Here, we review accumulating evidence suggesting that mitochondrial oxidative stress is involved in cancer, and discuss the role of the mitochondrial Prx III antioxidant system as a potential target for cancer therapy. We hope that this review will provide the basis for new strategic approaches in the development of effective cancer treatments. PMID- 22072942 TI - Roles of oxidative stress, apoptosis, PGC-1alpha and mitochondrial biogenesis in cerebral ischemia. AB - The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-gamma (PPARgamma) co-activator 1alpha (PGC1-alpha). PGC1-alpha is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-alpha is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis. PMID- 22072943 TI - Optimal production and biochemical properties of a lipase from Candida albicans. AB - Lipases from microorganisms have multi-faceted properties and play an important role in ever-growing modern biotechnology and, consequently, it is of great significance to develop new ones. In the present work, a lipase gene from Candida albicans (CaLIP10) was cloned and two non-unusual CUG serine codons were mutated into universal codons, and its expression in Pichia pastoris performed optimally, as shown by response surface methodology. Optimal conditions were: initial pH of culture 6.86, temperature 25.53 degrees C, 3.48% of glucose and 1.32% of yeast extract. The corresponding maximal lipolytic activity of CaLIP10 was 8.06 U/mL. The purified CaLIP10 showed maximal activity at pH 8.0 and 25 degrees C, and a good resistance to non-ionic surfactants and polar organic solvent was noticed. CaLIP10 could effectively hydrolyze coconut oil, but exhibited no obvious preference to the fatty acids with different carbon length, and diacylglycerol was accumulated in the reaction products, suggesting that CaLIP10 is a potential lipase for the oil industry. PMID- 22072944 TI - Use of oligonucleotides carrying photolabile groups for the control of the deposition of nanoparticles in surfaces and nanoparticle association. AB - An oligodeoxynucleotide hairpin containing a photolabile 2-nitrobenzyl group in the loop and terminated with a thiol function was prepared. The photocleavage of such a hairpin on gold yields a surface activated with a single stranded oligonucleotide which can be utilised to direct the assembly of nanoparticles conjugated with a complementary strand. Analysis of photocleaved surfaces gives nanoparticle coverage one order of magnitude higher than nonphotocleaved surfaces. This illustrates the ability of photocleavable hairpins to direct the assembly of nanomaterials on conducting materials. The conjugation of the photocleavable hairpin to a gold nanoparticle allows the observation of intermolecular interactions between hairpins linked in different nanoparticles, by comparing the thermal dissociations of a hairpin-nanoparticle conjugates at 260 nm and 520 nm. We have also shown that it is possible to permanently alter the physiochemical properties of DNA-nanoparticles by the introduction of a photocleavable group. Indeed for the first time it has been shown that by exposure to UV light the disassembly of nanoparticle aggregates can be induced. PMID- 22072939 TI - Manganese superoxide dismutase: guardian of the powerhouse. AB - The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as beta-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) acting as the chief ROS scavenging enzyme in the cell. Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases. A better understanding of the mechanisms by which MnSOD protects cells from the harmful effects of overproduction of ROS, in particular, the effects of ROS on mitochondrial metabolic enzymes, may contribute to the development of novel treatments for various diseases in which ROS are an important component. PMID- 22072945 TI - Estimating the octanol/water partition coefficient for aliphatic organic compounds using semi-empirical electrotopological index. AB - A new possibility for estimating the octanol/water coefficient (log P) was investigated using only one descriptor, the semi-empirical electrotopological index (I(SET)). The predictability of four octanol/water partition coefficient (log P) calculation models was compared using a set of 131 aliphatic organic compounds from five different classes. Log P values were calculated employing atomic-contribution methods, as in the Ghose/Crippen approach and its later refinement, AlogP; using fragmental methods through the ClogP method; and employing an approach considering the whole molecule using topological indices with the MlogP method. The efficiency and the applicability of the I(SET) in terms of calculating log P were demonstrated through good statistical quality (r > 0.99; s < 0.18), high internal stability and good predictive ability for an external group of compounds in the same order as the widely used models based on the fragmental method, ClogP, and the atomic contribution method, AlogP, which are among the most used methods of predicting log P. PMID- 22072946 TI - Isolation and characterization of 11 new microsatellite loci in Erigeron breviscapus (Asteraceae), an important Chinese traditional herb. AB - Erigeron breviscapus (Vant.) Hand.-Mazz. (Asteraceae) is a species endemic to southwestern China and an important traditional Chinese herb for cardiovascular and cerebral vessel diseases. Applying a modified biotin-streptavidin capture method, 11 microsatellite loci were discovered. Polymorphism of each locus was assessed in 24 individuals collected from five wild populations. The number of alleles per locus ranged from 2 to 7, with an average of 4.273. The observed (HO) and expected (HE) heterozygosities varied from 0.250 to 0.958 and from 0.337 to 0.786, respectively. Over half of these loci were successfully amplified in two congeneric species. The developed microsatellite markers will be useful for future population genetics and conservation studies, as well as accurate identification of different varieties. PMID- 22072947 TI - Eighteen years of molecular genotyping the hemophilia inversion hotspot: from southern blot to inverse shifting-PCR. AB - The factor VIII gene (F8) intron 22 inversion (Inv22) is a paradigmatic duplicon mediated rearrangement, found in about one half of patients with severe hemophilia A worldwide. The identification of this prevalent cause of hemophilia was delayed for nine years after the F8 characterization in 1984. The aim of this review is to present the wide diversity of practical approaches that have been developed for genotyping the Inv22 (and related int22h rearrangements) since discovery in 1993. The sequence- Southern blot, long distance-PCR and inverse shifting-PCR-for Inv22 genotyping is an interesting example of scientific ingenuity and evolution in order to resolve challenging molecular diagnostic problems. PMID- 22072948 TI - Dynamics of Word Comprehension in Infancy: Developments in Timing, Accuracy, and Resistance to Acoustic Degradation. AB - Online comprehension of naturally spoken and perceptually degraded words was assessed in 95 children ages 12 to 31 months. The time course of word recognition was measured by monitoring eye movements as children looked at pictures while listening to familiar target words presented in unaltered, time-compressed, and low-pass-filtered forms. Success in word recognition varied with age and level of vocabulary development, and with the perceptual integrity of the word. Recognition was best overall for unaltered words, lower for time-compressed words, and significantly lower in low-pass-filtered words. Reaction times were fastest in compressed, followed by unaltered and filtered words. Results showed that children were able to recognize familiar words in challenging conditions and that productive vocabulary size was more sensitive than chronological age as a predictor of children's accuracy and speed in word recognition. PMID- 22072950 TI - Transcriptomic coordination in the human metabolic network reveals links between n-3 fat intake, adipose tissue gene expression and metabolic health. AB - Understanding the molecular link between diet and health is a key goal in nutritional systems biology. As an alternative to pathway analysis, we have developed a joint multivariate and network-based approach to analysis of a dataset of habitual dietary records, adipose tissue transcriptomics and comprehensive plasma marker profiles from human volunteers with the Metabolic Syndrome. With this approach we identified prominent co-expressed sub-networks in the global metabolic network, which showed correlated expression with habitual n 3 PUFA intake and urinary levels of the oxidative stress marker 8-iso PGF(2alpha). These sub-networks illustrated inherent cross-talk between distinct metabolic pathways, such as between triglyceride metabolism and production of lipid signalling molecules. In a parallel promoter analysis, we identified several adipogenic transcription factors as potential transcriptional regulators associated with habitual n-3 PUFA intake. Our results illustrate advantages of network-based analysis, and generate novel hypotheses on the transcriptomic link between habitual n-3 PUFA intake, adipose tissue function and oxidative stress. PMID- 22072951 TI - How landscape heterogeneity frames optimal diffusivity in searching processes. AB - Theoretical and empirical investigations of search strategies typically have failed to distinguish the distinct roles played by density versus patchiness of resources. It is well known that motility and diffusivity of organisms often increase in environments with low density of resources, but thus far there has been little progress in understanding the specific role of landscape heterogeneity and disorder on random, non-oriented motility. Here we address the general question of how the landscape heterogeneity affects the efficiency of encounter interactions under global constant density of scarce resources. We unveil the key mechanism coupling the landscape structure with optimal search diffusivity. In particular, our main result leads to an empirically testable prediction: enhanced diffusivity (including superdiffusive searches), with shift in the diffusion exponent, favors the success of target encounters in heterogeneous landscapes. PMID- 22072952 TI - High degree of heterogeneity in Alzheimer's disease progression patterns. AB - There have been several reports on the varying rates of progression among Alzheimer's Disease (AD) patients; however, there has been no quantitative study of the amount of heterogeneity in AD. Obtaining a reliable quantitative measure of AD progression rates and their variances among the patients for each stage of AD is essential for evaluating results of any clinical study. The Global Deterioration Scale (GDS) and Functional Assessment Staging procedure (FAST) characterize seven stages in the course of AD from normal aging to severe dementia. Each GDS/FAST stage has a published mean duration, but the variance is unknown. We use statistical analysis to reconstruct GDS/FAST stage durations in a cohort of 648 AD patients with an average follow-up time of 4.78 years. Calculations for GDS/FAST stages 4-6 reveal that the standard deviations for stage durations are comparable with their mean values, indicating the presence of large variations in the AD progression among patients. Such amount of heterogeneity in the course of progression of AD is consistent with the existence of several sub-groups of AD patients, which differ by their patterns of decline. PMID- 22072953 TI - Learning the optimal control of coordinated eye and head movements. AB - Various optimality principles have been proposed to explain the characteristics of coordinated eye and head movements during visual orienting behavior. At the same time, researchers have suggested several neural models to underly the generation of saccades, but these do not include online learning as a mechanism of optimization. Here, we suggest an open-loop neural controller with a local adaptation mechanism that minimizes a proposed cost function. Simulations show that the characteristics of coordinated eye and head movements generated by this model match the experimental data in many aspects, including the relationship between amplitude, duration and peak velocity in head-restrained and the relative contribution of eye and head to the total gaze shift in head-free conditions. Our model is a first step towards bringing together an optimality principle and an incremental local learning mechanism into a unified control scheme for coordinated eye and head movements. PMID- 22072954 TI - The statistics of bulk segregant analysis using next generation sequencing. AB - We describe a statistical framework for QTL mapping using bulk segregant analysis (BSA) based on high throughput, short-read sequencing. Our proposed approach is based on a smoothed version of the standard G statistic, and takes into account variation in allele frequency estimates due to sampling of segregants to form bulks as well as variation introduced during the sequencing of bulks. Using simulation, we explore the impact of key experimental variables such as bulk size and sequencing coverage on the ability to detect QTLs. Counterintuitively, we find that relatively large bulks maximize the power to detect QTLs even though this implies weaker selection and less extreme allele frequency differences. Our simulation studies suggest that with large bulks and sufficient sequencing depth, the methods we propose can be used to detect even weak effect QTLs and we demonstrate the utility of this framework by application to a BSA experiment in the budding yeast Saccharomyces cerevisiae. PMID- 22072955 TI - Interspecies translation of disease networks increases robustness and predictive accuracy. AB - Gene regulatory networks give important insights into the mechanisms underlying physiology and pathophysiology. The derivation of gene regulatory networks from high-throughput expression data via machine learning strategies is problematic as the reliability of these models is often compromised by limited and highly variable samples, heterogeneity in transcript isoforms, noise, and other artifacts. Here, we develop a novel algorithm, dubbed Dandelion, in which we construct and train intraspecies Bayesian networks that are translated and assessed on independent test sets from other species in a reiterative procedure. The interspecies disease networks are subjected to multi-layers of analysis and evaluation, leading to the identification of the most consistent relationships within the network structure. In this study, we demonstrate the performance of our algorithms on datasets from animal models of oculopharyngeal muscular dystrophy (OPMD) and patient materials. We show that the interspecies network of genes coding for the proteasome provide highly accurate predictions on gene expression levels and disease phenotype. Moreover, the cross-species translation increases the stability and robustness of these networks. Unlike existing modeling approaches, our algorithms do not require assumptions on notoriously difficult one-to-one mapping of protein orthologues or alternative transcripts and can deal with missing data. We show that the identified key components of the OPMD disease network can be confirmed in an unseen and independent disease model. This study presents a state-of-the-art strategy in constructing interspecies disease networks that provide crucial information on regulatory relationships among genes, leading to better understanding of the disease molecular mechanisms. PMID- 22072956 TI - Stability properties of underdominance in finite subdivided populations. AB - IN ISOLATED populations underdominance leads to bistable evolutionary dynamics: below a certain mutant allele frequency the wildtype succeeds. Above this point, the potentially underdominant mutant allele fixes. In subdivided populations with gene flow there can be stable states with coexistence of wildtypes and mutants: polymorphism can be maintained because of a migration-selection equilibrium, i.e., selection against rare recent immigrant alleles that tend to be heterozygous. We focus on the stochastic evolutionary dynamics of systems where demographic fluctuations in the coupled populations are the main source of internal noise. We discuss the influence of fitness, migration rate, and the relative sizes of two interacting populations on the mean extinction times of a group of potentially underdominant mutant alleles. We classify realistic initial conditions according to their impact on the stochastic extinction process. Even in small populations, where demographic fluctuations are large, stability properties predicted from deterministic dynamics show remarkable robustness. Fixation of the mutant allele becomes unlikely but the time to its extinction can be long. PMID- 22072958 TI - Simple rapid near-patient diagnostics for tuberculosis remain elusive--is a "treat-to-test" strategy more realistic? PMID- 22072959 TI - SAG101 forms a ternary complex with EDS1 and PAD4 and is required for resistance signaling against turnip crinkle virus. AB - EDS1, PAD4, and SAG101 are common regulators of plant immunity against many pathogens. EDS1 interacts with both PAD4 and SAG101 but direct interaction between PAD4 and SAG101 has not been detected, leading to the suggestion that the EDS1-PAD4 and EDS1-SAG101 complexes are distinct. We show that EDS1, PAD4, and SAG101 are present in a single complex in planta. While this complex is preferentially nuclear localized, it can be redirected to the cytoplasm in the presence of an extranuclear form of EDS1. PAD4 and SAG101 can in turn, regulate the subcellular localization of EDS1. We also show that the Arabidopsis genome encodes two functionally redundant isoforms of EDS1, either of which can form ternary complexes with PAD4 and SAG101. Simultaneous mutations in both EDS1 isoforms are essential to abrogate resistance (R) protein-mediated defense against turnip crinkle virus (TCV) as well as avrRps4 expressing Pseudomonas syringae. Interestingly, unlike its function as a PAD4 substitute in bacterial resistance, SAG101 is required for R-mediated resistance to TCV, thus implicating a role for the ternary complex in this defense response. However, only EDS1 is required for HRT-mediated HR to TCV, while only PAD4 is required for SA-dependent induction of HRT. Together, these results suggest that EDS1, PAD4 and SAG101 also perform independent functions in HRT-mediated resistance. PMID- 22072960 TI - Assessing predicted HIV-1 replicative capacity in a clinical setting. AB - HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs) correlate significantly with the virus load measured in 2073 infected but drug naive individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load. PMID- 22072961 TI - BST2/Tetherin enhances entry of human cytomegalovirus. AB - Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV. PMID- 22072962 TI - Genomic transition to pathogenicity in chytrid fungi. AB - Understanding the molecular mechanisms of pathogen emergence is central to mitigating the impacts of novel infectious disease agents. The chytrid fungus Batrachochytrium dendrobatidis (Bd) is an emerging pathogen of amphibians that has been implicated in amphibian declines worldwide. Bd is the only member of its clade known to attack vertebrates. However, little is known about the molecular determinants of - or evolutionary transition to - pathogenicity in Bd. Here we sequence the genome of Bd's closest known relative - a non-pathogenic chytrid Homolaphlyctis polyrhiza (Hp). We first describe the genome of Hp, which is comparable to other chytrid genomes in size and number of predicted proteins. We then compare the genomes of Hp, Bd, and 19 additional fungal genomes to identify unique or recent evolutionary elements in the Bd genome. We identified 1,974 Bd specific genes, a gene set that is enriched for protease, lipase, and microbial effector Gene Ontology terms. We describe significant lineage-specific expansions in three Bd protease families (metallo-, serine-type, and aspartyl proteases). We show that these protease gene family expansions occurred after the divergence of Bd and Hp from their common ancestor and thus are localized to the Bd branch. Finally, we demonstrate that the timing of the protease gene family expansions predates the emergence of Bd as a globally important amphibian pathogen. PMID- 22072963 TI - The critical role of Notch ligand Delta-like 1 in the pathogenesis of influenza A virus (H1N1) infection. AB - Influenza A viral infections have been identified as the etiologic agents for historic pandemics, and contribute to the annual mortality associated with acute viral pneumonia. While both innate and acquired immunity are important in combating influenza virus infection, the mechanism connecting these arms of the immune system remains unknown. Recent data have indicated that the Notch system is an important bridge between antigen-presenting cells (APCs) and T cell communication circuits and plays a central role in driving the immune system to overcome disease. In the present study, we examine the role of Notch signaling during influenza H1N1 virus infection, focusing on APCs. We demonstrate here that macrophages, but not dendritic cells (DCs), increased Notch ligand Delta-like 1 (Dll1) expression following influenza virus challenge. Dll1 expression on macrophages was dependent on retinoic acid-inducible gene-I (RIG-I) induced type I IFN pathway, and not on the TLR3-TRIF pathway. We also found that IFNalpha Receptor knockout mice failed to induce Dll1 expression on lung macrophages and had enhanced mortality during influenza virus infection. Our results further showed that specific neutralization of Dll1 during influenza virus challenge induced higher mortality, impaired viral clearance, and decreased levels of IFN gamma. In addition, we blocked Notch signaling by using gamma-secretase inhibitor (GSI), a Notch signaling inhibitor. Intranasal administration of GSI during influenza infection also led to higher mortality, and higher virus load with excessive inflammation and an impaired production of IFN-gamma in lungs. Moreover, Dll1 expression on macrophages specifically regulates IFN-gamma levels from CD4(+)and CD8(+)T cells, which are important for anti-viral immunity. Together, the results of this study show that Dll1 positively influences the development of anti-viral immunity, and may provide mechanistic approaches for modifying and controlling the immune response against influenza H1N1 virus infection. PMID- 22072964 TI - Sequence-based analysis uncovers an abundance of non-coding RNA in the total transcriptome of Mycobacterium tuberculosis. AB - RNA sequencing provides a new perspective on the genome of Mycobacterium tuberculosis by revealing an extensive presence of non-coding RNA, including long 5' and 3' untranslated regions, antisense transcripts, and intergenic small RNA (sRNA) molecules. More than a quarter of all sequence reads mapping outside of ribosomal RNA genes represent non-coding RNA, and the density of reads mapping to intergenic regions was more than two-fold higher than that mapping to annotated coding sequences. Selected sRNAs were found at increased abundance in stationary phase cultures and accumulated to remarkably high levels in the lungs of chronically infected mice, indicating a potential contribution to pathogenesis. The ability of tubercle bacilli to adapt to changing environments within the host is critical to their ability to cause disease and to persist during drug treatment; it is likely that novel post-transcriptional regulatory networks will play an important role in these adaptive responses. PMID- 22072965 TI - Unique type I interferon responses determine the functional fate of migratory lung dendritic cells during influenza virus infection. AB - Migratory lung dendritic cells (DCs) transport viral antigen from the lungs to the draining mediastinal lymph nodes (MLNs) during influenza virus infection to initiate the adaptive immune response. Two major migratory DC subsets, CD103(+) DCs and CD11b(high) DCs participate in this function and it is not clear if these antigen presenting cell (APC) populations become directly infected and if so whether their activity is influenced by the infection. In these experiments we show that both subpopulations can become infected and migrate to the draining MLN but a difference in their response to type I interferon (I-IFN) signaling dictates the capacity of the virus to replicate. CD103(+) DCs allow the virus to replicate to significantly higher levels than do the CD11b(high) DCs, and they release infectious virus in the MLNs and when cultured ex-vivo. Virus replication in CD11b(high) DCs is inhibited by I-IFNs, since ablation of the I-IFN receptor (IFNAR) signaling permits virus to replicate vigorously and productively in this subset. Interestingly, CD103(+) DCs are less sensitive to I-IFNs upregulating interferon-induced genes to a lesser extent than CD11b(high) DCs. The attenuated IFNAR signaling by CD103(+) DCs correlates with their described superior antigen presentation capacity for naive CD8(+) T cells when compared to CD11b(high) DCs. Indeed ablation of IFNAR signaling equalizes the competency of the antigen presenting function for the two subpopulations. Thus, antigen presentation by lung DCs is proportional to virus replication and this is tightly constrained by I-IFN. The "interferon-resistant" CD103(+) DCs may have evolved to ensure the presentation of viral antigens to T cells in I-IFN rich environments. Conversely, this trait may be exploitable by viral pathogens as a mechanism for systemic dissemination. PMID- 22072966 TI - Rab7A is required for efficient production of infectious HIV-1. AB - Retroviruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Rab proteins regulate specific steps in intracellular membrane trafficking by recruiting tethering, docking and fusion factors, as well as the actin- and microtubule-based motor proteins that facilitate vesicle traffic. Using virological tests and RNA interference targeting Rab proteins, we demonstrate that the late endosome-associated Rab7A is required for HIV-1 propagation. Analysis of the late steps of the HIV infection cycle shows that Rab7A regulates Env processing, the incorporation of mature Env glycoproteins into viral particles and HIV-1 infectivity. We also show that siRNA mediated Rab7A depletion induces a BST2/Tetherin phenotype on HIV-1 release. BST2/Tetherin is a restriction factor that impedes HIV-1 release by tethering mature virus particles to the plasma membrane. Our results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release. Altogether, our results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle. PMID- 22072968 TI - Fatal prion disease in a mouse model of genetic E200K Creutzfeldt-Jakob disease. AB - Genetic prion diseases are late onset fatal neurodegenerative disorders linked to pathogenic mutations in the prion protein-encoding gene, PRNP. The most prevalent of these is the substitution of Glutamate for Lysine at codon 200 (E200K), causing genetic Creutzfeldt-Jakob disease (gCJD) in several clusters, including Jews of Libyan origin. Investigating the pathogenesis of genetic CJD, as well as developing prophylactic treatments for young asymptomatic carriers of this and other PrP mutations, may well depend upon the availability of appropriate animal models in which long term treatments can be evaluated for efficacy and toxicity. Here we present the first effective mouse model for E200KCJD, which expresses chimeric mouse/human (TgMHu2M) E199KPrP on both a null and a wt PrP background, as is the case for heterozygous patients and carriers. Mice from both lines suffered from distinct neurological symptoms as early as 5-6 month of age and deteriorated to death several months thereafter. Histopathological examination of the brain and spinal cord revealed early gliosis and age-related intraneuronal deposition of disease-associated PrP similarly to human E200K gCJD. Concomitantly we detected aggregated, proteinase K resistant, truncated and oxidized PrP forms on immunoblots. Inoculation of brain extracts from TgMHu2ME199K mice readily induced, the first time for any mutant prion transgenic model, a distinct fatal prion disease in wt mice. We believe that these mice may serve as an ideal platform for the investigation of the pathogenesis of genetic prion disease and thus for the monitoring of anti-prion treatments. PMID- 22072967 TI - Multiple candidate effectors from the oomycete pathogen Hyaloperonospora arabidopsidis suppress host plant immunity. AB - Oomycete pathogens cause diverse plant diseases. To successfully colonize their hosts, they deliver a suite of effector proteins that can attenuate plant defenses. In the oomycete downy mildews, effectors carry a signal peptide and an RxLR motif. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on the model plant Arabidopsis thaliana (Arabidopsis). We investigated if candidate effectors predicted in the genome sequence of Hpa isolate Emoy2 (HaRxLs) were able to manipulate host defenses in different Arabidopsis accessions. We developed a rapid and sensitive screening method to test HaRxLs by delivering them via the bacterial type-three secretion system (TTSS) of Pseudomonas syringae pv tomato DC3000-LUX (Pst-LUX) and assessing changes in Pst-LUX growth in planta on 12 Arabidopsis accessions. The majority (~70%) of the 64 candidates tested positively contributed to Pst-LUX growth on more than one accession indicating that Hpa virulence likely involves multiple effectors with weak accession specific effects. Further screening with a Pst mutant (DeltaCEL) showed that HaRxLs that allow enhanced Pst-LUX growth usually suppress callose deposition, a hallmark of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). We found that HaRxLs are rarely strong avirulence determinants. Although some decreased Pst-LUX growth in particular accessions, none activated macroscopic cell death. Fewer HaRxLs conferred enhanced Pst growth on turnip, a non-host for Hpa, while several reduced it, consistent with the idea that turnip's non-host resistance against Hpa could involve a combination of recognized HaRxLs and ineffective HaRxLs. We verified our results by constitutively expressing in Arabidopsis a sub-set of HaRxLs. Several transgenic lines showed increased susceptibility to Hpa and attenuation of Arabidopsis PTI responses, confirming the HaRxLs' role in Hpa virulence. This study shows TTSS screening system provides a useful tool to test whether candidate effectors from eukaryotic pathogens can suppress/trigger plant defense mechanisms and to rank their effectiveness prior to subsequent mechanistic investigation. PMID- 22072969 TI - Anti-filarial activity of antibiotic therapy is due to extensive apoptosis after Wolbachia depletion from filarial nematodes. AB - Filarial nematodes maintain a mutualistic relationship with the endosymbiont Wolbachia. Depletion of Wolbachia produces profound defects in nematode development, fertility and viability and thus has great promise as a novel approach for treating filarial diseases. However, little is known concerning the basis for this mutualistic relationship. Here we demonstrate using whole mount confocal microscopy that an immediate response to Wolbachia depletion is extensive apoptosis in the adult germline, and in the somatic cells of the embryos, microfilariae and fourth-stage larvae (L4). Surprisingly, apoptosis occurs in the majority of embryonic cells that had not been infected prior to antibiotic treatment. In addition, no apoptosis occurs in the hypodermal chords, which are populated with large numbers of Wolbachia, although disruption of the hypodermal cytoskeleton occurs following their depletion. Thus, the induction of apoptosis upon Wolbachia depletion is non-cell autonomous and suggests the involvement of factors originating from Wolbachia in the hypodermal chords. The pattern of apoptosis correlates closely with the nematode tissues and processes initially perturbed following depletion of Wolbachia, embryogenesis and long-term sterilization, which are sustained for several months until the premature death of the adult worms. Our observations provide a cellular mechanism to account for the sustained reductions in microfilarial loads and interruption of transmission that occurs prior to macrofilaricidal activity following antibiotic therapy of filarial nematodes. PMID- 22072970 TI - The pore-forming toxin listeriolysin O mediates a novel entry pathway of L. monocytogenes into human hepatocytes. AB - Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin listeriolysin O (LLO) facilitates bacterial escape from the internalization vesicle into the cytoplasm, where bacteria divide and undergo cell-to-cell spreading via actin-based motility. In the present study we demonstrate that in addition to InlA and InlB, LLO is required for efficient internalization of L. monocytogenes into human hepatocytes (HepG2). Surprisingly, LLO is an invasion factor sufficient to induce the internalization of noninvasive Listeria innocua or polystyrene beads into host cells in a dose-dependent fashion and at the concentrations produced by L. monocytogenes. To elucidate the mechanisms underlying LLO-induced bacterial entry, we constructed novel LLO derivatives locked at different stages of the toxin assembly on host membranes. We found that LLO-induced bacterial or bead entry only occurs upon LLO pore formation. Scanning electron and fluorescence microscopy studies show that LLO-coated beads stimulate the formation of membrane extensions that ingest the beads into an early endosomal compartment. This LLO-induced internalization pathway is dynamin-and F actin-dependent, and clathrin-independent. Interestingly, further linking pore formation to bacteria/bead uptake, LLO induces F-actin polymerization in a tyrosine kinase-and pore-dependent fashion. In conclusion, we demonstrate for the first time that a bacterial pathogen perforates the host cell plasma membrane as a strategy to activate the endocytic machinery and gain entry into the host cell. PMID- 22072971 TI - A molecular mechanism for bacterial susceptibility to zinc. AB - Transition row metal ions are both essential and toxic to microorganisms. Zinc in excess has significant toxicity to bacteria, and host release of Zn(II) at mucosal surfaces is an important innate defence mechanism. However, the molecular mechanisms by which Zn(II) affords protection have not been defined. We show that in Streptococcus pneumoniae extracellular Zn(II) inhibits the acquisition of the essential metal Mn(II) by competing for binding to the solute binding protein PsaA. We show that, although Mn(II) is the high-affinity substrate for PsaA, Zn(II) can still bind, albeit with a difference in affinity of nearly two orders of magnitude. Despite the difference in metal ion affinities, high-resolution structures of PsaA in complex with Mn(II) or Zn(II) showed almost no difference. However, Zn(II)-PsaA is significantly more thermally stable than Mn(II)-PsaA, suggesting that Zn(II) binding may be irreversible. In vitro growth analyses show that extracellular Zn(II) is able to inhibit Mn(II) intracellular accumulation with little effect on intracellular Zn(II). The phenotype of S. pneumoniae grown at high Zn(II):Mn(II) ratios, i.e. induced Mn(II) starvation, closely mimicked a DeltapsaA mutant, which is unable to accumulate Mn(II). S. pneumoniae infection in vivo elicits massive elevation of the Zn(II):Mn(II) ratio and, in vitro, these Zn(II):Mn(II) ratios inhibited growth due to Mn(II) starvation, resulting in heightened sensitivity to oxidative stress and polymorphonuclear leucocyte killing. These results demonstrate that microbial susceptibility to Zn(II) toxicity is mediated by extracellular cation competition and that this can be harnessed by the innate immune response. PMID- 22072972 TI - ChemR23 dampens lung inflammation and enhances anti-viral immunity in a mouse model of acute viral pneumonia. AB - Viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. Plasmacytoid dendritic cells play an important role in anti viral immunity, and these cells were recently shown to express ChemR23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. Our aim was to determine the role played by the chemerin/ChemR23 system in the physiopathology of viral pneumonia, using the pneumonia virus of mice (PVM) as a model. Wild-type and ChemR23 knock-out mice were infected by PVM and followed for functional and inflammatory parameters. ChemR23(-/-) mice displayed higher mortality/morbidity, alteration of lung function, delayed viral clearance and increased neutrophilic infiltration. We demonstrated in these mice a lower recruitment of plasmacytoid dendritic cells and a reduction in type I interferon production. The role of plasmacytoid dendritic cells was further addressed by performing depletion and adoptive transfer experiments as well as by the generation of chimeric mice, demonstrating two opposite effects of the chemerin/ChemR23 system. First, the ChemR23-dependent recruitment of plasmacytoid dendritic cells contributes to adaptive immune responses and viral clearance, but also enhances the inflammatory response. Second, increased morbidity/mortality in ChemR23(-/-) mice is not due to defective plasmacytoid dendritic cells recruitment, but rather to the loss of an anti-inflammatory pathway involving ChemR23 expressed by non-leukocytic cells. The chemerin/ChemR23 system plays important roles in the physiopathology of viral pneumonia, and might therefore be considered as a therapeutic target for anti viral and anti-inflammatory therapies. PMID- 22072973 TI - Sap transporter mediated import and subsequent degradation of antimicrobial peptides in Haemophilus. AB - Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the upper and lower respiratory tracts. An important aspect of NTHI virulence is the ability to avert bactericidal effects of host-derived antimicrobial peptides (AMPs). The Sap (sensitivity to antimicrobial peptides) ABC transporter equips NTHI to resist AMPs, although the mechanism of this resistance has remained undefined. We previously determined that the periplasmic binding protein SapA bound AMPs and was required for NTHI virulence in vivo. We now demonstrate, by antibody-mediated neutralization of AMP in vivo, that SapA functions to directly counter AMP lethality during NTHI infection. We hypothesized that SapA would deliver AMPs to the Sap inner membrane complex for transport into the bacterial cytoplasm. We observed that AMPs localize to the bacterial cytoplasm of the parental NTHI strain and were susceptible to cytoplasmic peptidase activity. In striking contrast, AMPs accumulated in the periplasm of bacteria lacking a functional Sap permease complex. These data support a mechanism of Sap mediated import of AMPs, a novel strategy to reduce periplasmic and inner membrane accumulation of these host defense peptides. PMID- 22072974 TI - Single molecule analysis of replicated DNA reveals the usage of multiple KSHV genome regions for latent replication. AB - Kaposi's sarcoma associated herpesvirus (KSHV), an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA). Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD). Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR) plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA sequences. PMID- 22072975 TI - A LysM and SH3-domain containing region of the Listeria monocytogenes p60 protein stimulates accessory cells to promote activation of host NK cells. AB - Listeria monocytogenes (Lm) infection induces rapid and robust activation of host natural killer (NK) cells. Here we define a region of the abundantly secreted Lm endopeptidase, p60, that potently but indirectly stimulates NK cell activation in vitro and in vivo. Lm expression of p60 resulted in increased IFNgamma production by naive NK cells co-cultured with treated dendritic cells (DCs). Moreover, recombinant p60 protein stimulated activation of naive NK cells when co-cultured with TLR or cytokine primed DCs in the absence of Lm. Intact p60 protein weakly digested bacterial peptidoglycan (PGN), but neither muropeptide recognition by RIP2 nor the catalytic activity of p60 was required for NK cell activation. Rather, the immune stimulating activity mapped to an N-terminal region of p60, termed L1S. Treatment of DCs with a recombinant L1S polypeptide stimulated them to activate naive NK cells in a cell culture model. Further, L1S treatment activated NK cells in vivo and increased host resistance to infection with Francisella tularensis live vaccine strain (LVS). These studies demonstrate an immune stimulating function for a bacterial LysM domain-containing polypeptide and suggest that recombinant versions of L1S or other p60 derivatives can be used to promote NK cell activation in therapeutic contexts. PMID- 22072977 TI - Drosophila duplication hotspots are associated with late-replicating regions of the genome. AB - Duplications play a significant role in both extremes of the phenotypic spectrum of newly arising mutations: they can have severe deleterious effects (e.g. duplications underlie a variety of diseases) but can also be highly advantageous. The phenotypic potential of newly arisen duplications has stimulated wide interest in both the mutational and selective processes shaping these variants in the genome. Here we take advantage of the Drosophila simulans-Drosophila melanogaster genetic system to further our understanding of both processes. Regarding mutational processes, the study of two closely related species allows investigation of the potential existence of shared duplication hotspots, and the similarities and differences between the two genomes can be used to dissect its underlying causes. Regarding selection, the difference in the effective population size between the two species can be leveraged to ask questions about the strength of selection acting on different classes of duplications. In this study, we conducted a survey of duplication polymorphisms in 14 different lines of D. simulans using tiling microarrays and combined it with an analogous survey for the D. melanogaster genome. By integrating the two datasets, we identified duplication hotspots conserved between the two species. However, unlike the duplication hotspots identified in mammalian genomes, Drosophila duplication hotspots are not associated with sequences of high sequence identity capable of mediating non-allelic homologous recombination. Instead, Drosophila duplication hotspots are associated with late-replicating regions of the genome, suggesting a link between DNA replication and duplication rates. We also found evidence supporting a higher effectiveness of selection on duplications in D. simulans than in D. melanogaster. This is also true for duplications segregating at high frequency, where we find evidence in D. simulans that a sizeable fraction of these mutations is being driven to fixation by positive selection. PMID- 22072978 TI - Over-expression of DSCAM and COL6A2 cooperatively generates congenital heart defects. AB - A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS), which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD), and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ~50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders. PMID- 22072979 TI - Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but is dispensable for medullary sublineage divergence. AB - The forkhead transcription factor Foxn1 is indispensable for thymus development, but the mechanisms by which it mediates thymic epithelial cell (TEC) development are poorly understood. To examine the cellular and molecular basis of Foxn1 function, we generated a novel and revertible hypomorphic allele of Foxn1. By varying levels of its expression, we identified a number of features of the Foxn1 system. Here we show that Foxn1 is a powerful regulator of TEC differentiation that is required at multiple intermediate stages of TE lineage development in the fetal and adult thymus. We find no evidence for a role for Foxn1 in TEC fate choice. Rather, we show it is required for stable entry into both the cortical and medullary TEC differentiation programmes and subsequently is needed at increasing dosage for progression through successive differentiation states in both cortical and medullary TEC. We further demonstrate regulation by Foxn1 of a suite of genes with diverse roles in thymus development and/or function, suggesting it acts as a master regulator of the core thymic epithelial programme rather than regulating a particular aspect of TEC biology. Overall, our data establish a genetics-based model of cellular hierarchies in the TE lineage and provide mechanistic insight relating titration of a single transcription factor to control of lineage progression. Our novel revertible hypomorph system may be similarly applied to analyzing other regulators of development. PMID- 22072980 TI - Attenuation of the sensing capabilities of PhoQ in transition to obligate insect bacterial association. AB - Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a regulator of key virulence determinants. In the current study, we show that the inactivation of the response regulator, phoP, renders S. glossinidius sensitive to insect derived cationic antimicrobial peptides (AMPs). The resulting mutant strain displays reduced expression of genes involved in the structural modification of lipid A that facilitates resistance to AMPs. In addition, the inactivation of phoP alters the expression of type-III secretion system (TTSS) genes encoded within three distinct chromosomal regions, indicating that PhoP PhoQ also serves as a master regulator of TTSS gene expression. In the absence of phoP, S. glossinidius is unable to superinfect either its natural tsetse fly host or a closely related hippoboscid louse fly. Furthermore, we show that the S. glossinidius PhoQ sensor kinase has undergone functional adaptations that result in a substantially diminished ability to sense ancestral signals. The loss of PhoQ's sensory capability is predicted to represent a novel adaptation to the static symbiotic lifestyle, allowing S. glossinidius to constitutively express genes that facilitate resistance to host derived AMPs. PMID- 22072981 TI - Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis. AB - Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks (DSBs) to form crossovers. Repair is biased toward using the homolog as a substrate rather than the sister chromatid. Pch2 is a conserved member of the AAA(+)-ATPase family of proteins and is implicated in a wide range of meiosis-specific processes including the recombination checkpoint, maturation of the chromosome axis, crossover control, and synapsis. We demonstrate a role for Pch2 in promoting and regulating interhomolog bias and the meiotic recombination checkpoint in response to unprocessed DSBs through the activation of axial proteins Hop1 and Mek1 in budding yeast. We show that Pch2 physically interacts with the putative BRCT repeats in the N-terminal region of Xrs2, a member of the MRX complex that acts at sites of unprocessed DSBs. Pch2, Xrs2, and the ATM ortholog Tel1 function in the same pathway leading to the phosphorylation of Hop1, independent of Rad17 and the ATR ortholog Mec1, which respond to the presence of single-stranded DNA. An N-terminal deletion of Xrs2 recapitulates the pch2Delta phenotypes for signaling unresected breaks. We propose that interaction with Xrs2 may enable Pch2 to remodel chromosome structure adjacent to the site of a DSB and thereby promote accessibility of Hop1 to the Tel1 kinase. In addition, Xrs2, like Pch2, is required for checkpoint mediated delay conferred by the failure to synapse chromosomes. PMID- 22072982 TI - Recessive antimorphic alleles overcome functionally redundant loci to reveal TSO1 function in Arabidopsis flowers and meristems. AB - Arabidopsis TSO1 encodes a protein with conserved CXC domains known to bind DNA and is homologous to animal proteins that function in chromatin complexes. tso1 mutants fall into two classes due to their distinct phenotypes. Class I, represented by two different missense mutations in the CXC domain, leads to failure in floral organ development, sterility, and fasciated inflorescence meristems. Class II, represented by a nonsense mutation and a T-DNA insertion line, develops wild-type-like flowers and inflorescences but shows severely reduced fertility. The phenotypic variability of tso1 alleles presents challenges in determining the true function of TSO1. In this study, we use artificial microRNA, double mutant analysis, and bimolecular fluorescence complementation assay to investigate the molecular basis underlying these two distinct classes of phenotypes. We show that the class I mutants could be converted into class II by artificial microRNA knockdown of the tso1 mutant transcript, suggesting that class I alleles produce antimorphic mutant proteins that interfere with functionally redundant loci. We identified one such redundant factor coded by the closely related TSO1 homolog SOL2. We show that the class I phenotype can be mimicked by knocking out both TSO1 and its homolog SOL2 in double mutants. Such antimorphic alleles targeting redundant factors are likely prevalent in Arabidopsis and maybe common in organisms with many sets of paralogous genes such as human. Our data challenge the conventional view that recessive alleles are always hypomorphic or null and that antimorphic alleles are always dominant. This study shows that recessive alleles can also be antimorphic and can produce a phenotype more severe than null by interfering with the function of related loci. This finding adds a new paradigm to classical genetic concepts, with important implications for future genetic studies both in basic research as well as in agriculture and medicine. PMID- 22072983 TI - Genome-wide crossover distribution in Arabidopsis thaliana meiosis reveals sex specific patterns along chromosomes. AB - In most species, crossovers (COs) are essential for the accurate segregation of homologous chromosomes at the first meiotic division. Their number and location are tightly regulated. Here, we report a detailed, genome-wide characterization of the rate and localization of COs in Arabidopsis thaliana, in male and female meiosis. We observed dramatic differences between male and female meiosis which included: (i) genetic map length; 575 cM versus 332 cM respectively; (ii) CO distribution patterns: male CO rates were very high at both ends of each chromosome, whereas female CO rates were very low; (iii) correlations between CO rates and various chromosome features: female CO rates correlated strongly and negatively with GC content and gene density but positively with transposable elements (TEs) density, whereas male CO rates correlated positively with the CpG ratio. However, except for CpG, the correlations could be explained by the unequal repartition of these sequences along the Arabidopsis chromosome. For both male and female meiosis, the number of COs per chromosome correlates with chromosome size expressed either in base pairs or as synaptonemal complex length. Finally, we show that interference modulates the CO distribution both in male and female meiosis. PMID- 22072984 TI - Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. AB - Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some susceptibility alleles for autoimmune diseases may be maintained in human population due to past selective processes. PMID- 22072985 TI - SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression. AB - Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9-GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between these opposing modes of transcriptional control by SOX9 may be mediated by cooperation with different partners such as GLI factors. PMID- 22072986 TI - A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened. AB - Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling. PMID- 22072988 TI - Short day-mediated cessation of growth requires the downregulation of AINTEGUMENTALIKE1 transcription factor in hybrid aspen. AB - Day length is a key environmental cue regulating the timing of major developmental transitions in plants. For example, in perennial plants such as the long-lived trees of the boreal forest, exposure to short days (SD) leads to the termination of meristem activity and bud set (referred to as growth cessation). The mechanism underlying SD-mediated induction of growth cessation is poorly understood. Here we show that the AIL1-AIL4 (AINTEGUMENTALIKE) transcription factors of the AP2 family are the downstream targets of the SD signal in the regulation of growth cessation response in hybrid aspen trees. AIL1 is expressed in the shoot apical meristem and leaf primordia, and exposure to SD signal downregulates AIL1 expression. Downregulation of AIL gene expression by SDs is altered in transgenic hybrid aspen plants that are defective in SD perception and/or response, e.g. PHYA or FT overexpressors. Importantly, SD-mediated regulation of growth cessation response is also affected by overexpression or downregulation of AIL gene expression. AIL1 protein can interact with the promoter of the key cell cycle genes, e.g. CYCD3.2, and downregulation of the expression of D-type cyclins after SD treatment is prevented by AIL1 overexpression. These data reveal that execution of SD-mediated growth cessation response requires the downregulation of AIL gene expression. Thus, while early acting components like PHYA and the CO/FT regulon are conserved in day-length regulation of flowering time and growth cessation between annual and perennial plants, signaling pathways downstream of SD perception diverge, with AIL transcription factors being novel targets of the CO/FT regulon connecting the perception of SD signal to the regulation of meristem activity. PMID- 22072987 TI - Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence. AB - Cellular senescence involves epigenetic alteration, e.g. loss of H3K27me3 in Ink4a-Arf locus. Using mouse embryonic fibroblast (MEF), we here analyzed transcription and epigenetic alteration during Ras-induced senescence on genome wide scale by chromatin immunoprecipitation (ChIP)-sequencing and microarray. Bmp2 was the most activated secreted factor with H3K4me3 gain and H3K27me3 loss, whereas H3K4me3 loss and de novo formation of H3K27me3 occurred inversely in repression of nine genes, including two BMP-SMAD inhibitors Smad6 and Noggin. DNA methylation alteration unlikely occurred. Ras-activated cells senesced with nuclear accumulation of phosphorylated SMAD1/5/8. Senescence was bypassed in Ras activated cells when Bmp2/Smad1 signal was blocked by Bmp2 knockdown, Smad6 induction, or Noggin induction. Senescence was induced when recombinant BMP2 protein was added to Bmp2-knocked-down Ras-activated cells. Downstream Bmp2-Smad1 target genes were then analyzed genome-wide by ChIP-sequencing using anti-Smad1 antibody in MEF that was exposed to BMP2. Smad1 target sites were enriched nearby transcription start sites of genes, which significantly correlated to upregulation by BMP2 stimulation. While Smad6 was one of Smad1 target genes to be upregulated by BMP2 exposure, Smad6 repression in Ras-activated cells with increased enrichment of Ezh2 and gain of H3K27me3 suggested epigenetic disruption of negative feedback by Polycomb. Among Smad1 target genes that were upregulated in Ras-activated cells without increased repressive mark, Parvb was found to contribute to growth inhibition as Parvb knockdown lead to escape from senescence. It was revealed through genome-wide analyses in this study that Bmp2 Smad1 signal and its regulation by harmonized epigenomic alteration play an important role in Ras-induced senescence. PMID- 22072990 TI - Legitimacy and fairness in priority setting in Tanzania. PMID- 22072989 TI - PcG complexes set the stage for epigenetic inheritance of gene silencing in early S phase before replication. AB - Polycomb group (PcG) proteins are part of a conserved cell memory system that conveys epigenetic inheritance of silenced transcriptional states through cell division. Despite the considerable amount of information about PcG mechanisms controlling gene silencing, how PcG proteins maintain repressive chromatin during epigenome duplication is still unclear. Here we identified a specific time window, the early S phase, in which PcG proteins are recruited at BX-C PRE target sites in concomitance with H3K27me3 repressive mark deposition. Notably, these events precede and are uncoupled from PRE replication timing, which occurs in late S phase when most epigenetic signatures are reduced. These findings shed light on one of the key mechanisms for PcG-mediated epigenetic inheritance during S phase, suggesting a conserved model in which the PcG-dependent H3K27me3 mark is inherited by dilution and not by de novo methylation occurring at the time of replication. PMID- 22072991 TI - Strengthening fairness, transparency and accountability in health care priority setting at district level in Tanzania. AB - Health care systems are faced with the challenge of resource scarcity and have insufficient resources to respond to all health problems and target groups simultaneously. Hence, priority setting is an inevitable aspect of every health system. However, priority setting is complex and difficult because the process is frequently influenced by political, institutional and managerial factors that are not considered by conventional priority-setting tools. In a five-year EU supported project, which started in 2006, ways of strengthening fairness and accountability in priority setting in district health management were studied. This review is based on a PhD thesis that aimed to analyse health care organisation and management systems, and explore the potential and challenges of implementing Accountability for Reasonableness (A4R) approach to priority setting in Tanzania. A qualitative case study in Mbarali district formed the basis of exploring the sociopolitical and institutional contexts within which health care decision making takes place. The study also explores how the A4R intervention was shaped, enabled and constrained by the contexts. Key informant interviews were conducted. Relevant documents were also gathered and group priority-setting processes in the district were observed. The study revealed that, despite the obvious national rhetoric on decentralisation, actual practice in the district involved little community participation. The assumption that devolution to local government promotes transparency, accountability and community participation, is far from reality. The study also found that while the A4R approach was perceived to be helpful in strengthening transparency, accountability and stakeholder engagement, integrating the innovation into the district health system was challenging. This study underscores the idea that greater involvement and accountability among local actors may increase the legitimacy and fairness of priority-setting decisions. A broader and more detailed analysis of health system elements, and socio-cultural context is imperative in fostering sustainability. Additionally, the study stresses the need to deal with power asymmetries among various actors in priority-setting contexts. PMID- 22072992 TI - New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities. AB - Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro). The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range. PMID- 22072993 TI - Design of new alpha-conotoxins: from computer modeling to synthesis of potent cholinergic compounds. AB - A series of 14 new analogs of alpha-conotoxin PnIA Conus pennaceus was synthesized and tested for binding to the human alpha7 nicotinic acetylcholine receptor (nAChR) and acetylcholine-binding proteins (AChBP) Lymnaea stagnalis and Aplysia californica. Based on computer modeling and the X-ray structure of the A. californica AChBP complex with the PnIA[A10L, D14K] analog, single and multiple amino acid substitutions were introduced in alpha-conotoxin PnIA aimed at compounds of higher affinity and selectivity. Three analogs, PnIA[L5H], PnIA[A10L, D14K] and PnIA[L5R, A10L, D14R], have high affinities for AChBPs or alpha7 nAChR, as found in competition with radioiodinated alpha-bungarotoxin. That is why we prepared radioiodinated derivatives of these alpha-conotoxins, demonstrated their specific binding and found that among the tested synthetic analogs, most had almost 10-fold higher affinity in competition with radioactive alpha-conotoxins as compared to competition with radioactive alpha-bungarotoxin. Thus, radioiodinated alpha-conotoxins are a more sensitive tool for checking the activity of novel alpha-conotoxins and other compounds quickly dissociating from the receptor complexes. PMID- 22072994 TI - Seasonal dynamics of Microcystis spp. and their toxigenicity as assessed by qPCR in a temperate reservoir. AB - Blooms of toxic cyanobacteria are becoming increasingly frequent, mainly due to water quality degradation. This work applied qPCR as a tool for early warning of microcystin(MC)-producer cyanobacteria and risk assessment of water supplies. Specific marker genes for cyanobacteria, Microcystis and MC-producing Microcystis, were quantified to determine the genotypic composition of the natural Microcystis population. Correlations between limnological parameters, pH, water temperature, dissolved oxygen and conductivity and MC concentrations as well as Microcystis abundance were assessed. A negative significant correlation was observed between toxic (with mcy genes) to non-toxic (without mcy genes) genotypes ratio and the overall Microcystis density. The highest proportions of toxic Microcystis genotypes were found 4-6 weeks before and 8-10 weeks after the peak of the bloom, with the lowest being observed at its peak. These results suggest positive selection of non-toxic genotypes under favorable environmental growth conditions. Significant positive correlations could be found between quantity of toxic genotypes and MC concentration, suggesting that the method applied can be useful to predict potential MC toxicity risk. No significant correlation was found between the limnological parameters measured and MC concentrations or toxic genotypes proportions indicating that other abiotic and biotic factors should be governing MC production and toxic genotypes dynamics. The qPCR method here applied is useful to rapidly estimate the potential toxicity of environmental samples and so, it may contribute to the more efficient management of water use in eutrophic systems. PMID- 22072995 TI - Therapies from fucoidan; multifunctional marine polymers. AB - Published research on fucoidans increased three fold between 2000 and 2010. These algal derived marine carbohydrate polymers present numerous valuable bioactivities. This review discusses the role for fucoidan in the control of acute and chronic inflammation via selectin blockade, enzyme inhibition and inhibiting the complement cascade. The recent data on toxicology and uptake of fucoidan is detailed together with a discussion on the comparative activities of fractions of fucoidan from different sources. Recent in vivo, in vitro and clinical research related to diverse clinical needs is discussed. Targets include osteoarthritis, kidney and liver disease, neglected infectious diseases, hemopoietic stem cell modulation, protection from radiation damage and treatments for snake envenomation. In recent years, the production of well characterized reproducible fucoidan fractions on a commercial scale has become possible making therapies from fucoidan a realizable goal. PMID- 22072996 TI - High-value components and bioactives from sea cucumbers for functional foods--a review. AB - Sea cucumbers, belonging to the class Holothuroidea, are marine invertebrates, habitually found in the benthic areas and deep seas across the world. They have high commercial value coupled with increasing global production and trade. Sea cucumbers, informally named as beche-de-mer, or gamat, have long been used for food and folk medicine in the communities of Asia and Middle East. Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as Vitamin A, Vitamin B1 (thiamine), Vitamin B2 (riboflavin), Vitamin B3 (niacin), and minerals, especially calcium, magnesium, iron and zinc. A number of unique biological and pharmacological activities including anti-angiogenic, anticancer, anticoagulant, anti-hypertension, anti-inflammatory, antimicrobial, antioxidant, antithrombotic, antitumor and wound healing have been ascribed to various species of sea cucumbers. Therapeutic properties and medicinal benefits of sea cucumbers can be linked to the presence of a wide array of bioactives especially triterpene glycosides (saponins), chondroitin sulfates, glycosaminoglycan (GAGs), sulfated polysaccharides, sterols (glycosides and sulfates), phenolics, cerberosides, lectins, peptides, glycoprotein, glycosphingolipids and essential fatty acids. This review is mainly designed to cover the high-value components and bioactives as well as the multiple biological and therapeutic properties of sea cucumbers with regard to exploring their potential uses for functional foods and nutraceuticals. PMID- 22072997 TI - Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health. AB - The marine carotenoid fucoxanthin can be found in marine brown seaweeds, the macroalgae, and diatoms, the microalgae, and has remarkable biological properties. Numerous studies have shown that fucoxanthin has considerable potential and promising applications in human health. In this article, we review the current available scientific literature regarding the metabolism, safety, and bioactivities of fucoxanthin, including its antioxidant, anti-inflammatory, anticancer, anti-obese, antidiabetic, antiangiogenic and antimalarial activities, and its protective effects on the liver, blood vessels of the brain, bones, skin, and eyes. Although some studies have shown the bioavailability of fucoxanthin in brown seaweeds to be low in humans, many studies have suggested that a dietary combination of fucoxanthin and edible oil or lipid could increase the absorption rate of fucoxanthin, and thus it might be a promising marine drug. PMID- 22072998 TI - Polyhydroxylated steroids from the bamboo coral Isis hippuris. AB - In previous studies on the secondary metabolites of the Taiwanese octocoral Isis hippuris, specimens have always been collected at Green Island. In the course of our studies on bioactive compounds from marine organisms, the acetone-solubles of the Taiwanese octocoral I. hippuris collected at Orchid Island have led to the isolation of five new polyoxygenated steroids: hipposterone M-O (1-3), hipposterol G (4) and hippuristeroketal A (5). The structures of these compounds were determined on the basis of their spectroscopic and physical data. The anti HCMV (human cytomegalovirus) activity of 1-5 and their cytotoxicity against selected cell lines were evaluated. Compound 2 exhibited inhibitory activity against HCMV, with an EC(50) value of 6.0 MUg/mL. PMID- 22073001 TI - Studies on synthesis and structure-activity relationship (SAR) of derivatives of a new natural product from marine fungi as inhibitors of influenza virus neuraminidase. AB - Based on the natural isoprenyl phenyl ether from a mangrove-derived fungus, 32 analogues were synthesized and evaluated for inhibitory activity against influenza H1N1 neuraminidase. Compound 15 (3-(allyloxy)-4-hydroxybenzaldehyde) exhibited the most potent inhibitory activity, with IC(50) values of 26.96 MUM for A/GuangdongSB/01/2009 (H1N1), 27.73 MUM for A/Guangdong/03/2009 (H1N1), and 25.13 MUM for A/Guangdong/ 05/2009 (H1N1), respectively, which is stronger than the benzoic acid derivatives (~mM level). These are a new kind of non-nitrogenous aromatic ether Neuraminidase (NA) inhibitors. Their structures are simple and the synthesis routes are not complex. The structure-activity relationship (SAR) analysis revealed that the aryl aldehyde and unsubstituted hydroxyl were important to NA inhibitory activities. Molecular docking studies were carried out to explain the SAR of the compounds, and provided valuable information for further structure modification. PMID- 22073000 TI - Cnidarians as a source of new marine bioactive compounds--an overview of the last decade and future steps for bioprospecting. AB - Marine invertebrates are rich sources of bioactive compounds and their biotechnological potential attracts scientific and economic interest worldwide. Although sponges are the foremost providers of marine bioactive compounds, cnidarians are also being studied with promising results. This diverse group of marine invertebrates includes over 11,000 species, 7500 of them belonging to the class Anthozoa. We present an overview of some of the most promising marine bioactive compounds from a therapeutic point of view isolated from cnidarians in the first decade of the 21st century. Anthozoan orders Alcyonacea and Gorgonacea exhibit by far the highest number of species yielding promising compounds. Antitumor activity has been the major area of interest in the screening of cnidarian compounds, the most promising ones being terpenoids (monoterpenoids, diterpenoids, sesquiterpenoids). We also discuss the future of bioprospecting for new marine bioactive compounds produced by cnidarians. PMID- 22072999 TI - Antitumor peptides from marine organisms. AB - The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides. PMID- 22073002 TI - Antiparasitic bromotyrosine derivatives from the marine sponge Verongula rigida. AB - Nine bromotyrosine-derived compounds were isolated from the Caribbean marine sponge Verongula rigida. Two of them, aeroplysinin-1 (1) and dihydroxyaerothionin (2), are known compounds for this species, and the other seven are unknown compounds for this species, namely: 3,5-dibromo-N,N,N-trimethyltyraminium (3), 3,5-dibromo-N,N,N, O-tetramethyltyraminium (4), purealidin R (5), 19 deoxyfistularin 3 (6), purealidin B (7), 11-hydroxyaerothionin (8) and fistularin 3 (9). Structural determination of the isolated compounds was performed using one and two-dimensional NMR, MS and other spectroscopy data. All isolated compounds were screened for their in vitro activity against three parasitic protozoa: Leishmania panamensis, Plasmodium falciparum and Trypanosoma cruzi. Compounds 7 and 8 showed selective antiparasitic activity at 10 and 5 MUM against Leishmania and Plasmodium parasites, respectively. Cytotoxicity of these compounds on a human promonocytic cell line was also assessed. PMID- 22073004 TI - Bioactive cembranoids from the soft coral Sinularia crassa. AB - Eight new cembranoids, crassarines A-H (1-8) were isolated from the Formosan soft coral Sinularia crassa. Compounds 1-3 represent the rare cembranoids with a 1,12 oxa-bridged tetrahydrofuran ring, while 4 and 5 are the firstly discovered 1,11 oxa-bridged tetrahydropyranocembranoids. The absolute configuration of 6 was determined using the Mosher's method. Compounds 6 and 8 were found to significantly inhibit the expression of both pro-inflammatory iNOS and COX-2 proteins at 10 MUM, respectively, while compounds 4-8 were found to be non cytotoxic toward the selected human liver cancer cells. PMID- 22073005 TI - Inducible ASABF-type antimicrobial peptide from the sponge Suberites domuncula: microbicidal and hemolytic activity in vitro and toxic effect on molluscs in vivo. AB - Since sponges, as typical filter-feeders, are exposed to a high load of attacking prokaryotic and eukaryotic organisms, they are armed with a wide arsenal of antimicrobial/cytostatic low-molecular-weight, non-proteinaceous bioactive compounds. Here we present the first sponge agent belonging to the group of ASABF type antimicrobial peptides. The ASABF gene was identified and cloned from the demosponge Suberites domuncula. The mature peptide, with a length of 64 aa residues has a predicted pI of 9.24, and comprises the characteristic CSalpha beta structural motif. Consequently, the S. domuncula ASABF shares high similarity with the nematode ASABFs; it is distantly related to the defensins. The recombinant peptide was found to display besides microbicidal activity, anti fungal activity. In addition, the peptide lyses human erythrocytes. The expression of ASABF is upregulated after exposure to the apoptosis-inducing agent 2,2'-dipyridyl. During the process of apoptosis of surface tissue of S. domuncula, grazing gastropods (Bittium sp.) are attracted by quinolinic acid which is synthesized through the kynurenine pathway by the enzyme 3 hydroxyanthranilate 3,4-dioxygenase (HAD). Finally, the gastropods are repelled from the sponge tissue by the ASABF. It is shown that the effector peptide ASABF is sequentially expressed after the induction of the HAD gene and a caspase, as a central enzyme executing apoptosis. PMID- 22073003 TI - The structural diversity of carbohydrate antigens of selected gram-negative marine bacteria. AB - Marine microorganisms have evolved for millions of years to survive in the environments characterized by one or more extreme physical or chemical parameters, e.g., high pressure, low temperature or high salinity. Marine bacteria have the ability to produce a range of biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents, and as a result, they have been a topic of research interest for many years. Among these biologically active molecules, the carbohydrate antigens, lipopolysaccharides (LPSs, O-antigens) found in cell walls of gram-negative marine bacteria, show great potential as candidates in the development of drugs to prevent septic shock due to their low virulence. The structural diversity of LPSs is thought to be a reflection of the ability for these bacteria to adapt to an array of habitats, protecting the cell from being compromised by exposure to harsh environmental stress factors. Over the last few years, the variety of structures of core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been discovered. In this review, we discuss the most recently encountered structures that have been identified from bacteria belonging to the genera Aeromonas, Alteromonas, Idiomarina, Microbulbifer, Pseudoalteromonas, Plesiomonas and Shewanella of the Gammaproteobacteria phylum; Sulfitobacter and Loktanella of the Alphaproteobactera phylum and to the genera Arenibacter, Cellulophaga, Chryseobacterium, Flavobacterium, Flexibacter of the Cytophaga-Flavobacterium-Bacteroides phylum. Particular attention is paid to the particular chemical features of the LPSs, such as the monosaccharide type, non sugar substituents and phosphate groups, together with some of the typifying traits of LPSs obtained from marine bacteria. A possible correlation is then made between such features and the environmental adaptations undertaken by marine bacteria. PMID- 22073006 TI - Pardaxin, an antimicrobial peptide, triggers caspase-dependent and ROS-mediated apoptosis in HT-1080 cells. AB - Pardaxin is an antimicrobial peptide (AMP) that was first isolated from secretions of the Red Sea Moses sole. The role of pardaxin in inducing apoptosis for preventing cancer has not yet been investigated. In the present study, we examined the antitumor activity of pardaxin against human fibrosarcoma HT-1080 cells; pardaxin inhibited cell proliferation by inducing apoptosis, as demonstrated by an increase in the externalization of plasma membrane phosphatidylserine and the presence of chromatin condensation. Additionally, pardaxin-treated cells showed elevation of caspase-3/7 activities, disruption of the mitochondrial membrane potential, and accumulation of reactive oxygen species (ROS) production. Inhibition of ROS production and caspase-3/7 activities reduced pardaxin-induced effects. Taken together, these findings suggest that pardaxin may be a potential anticancer agent for selectively inducing apoptosis in cancer cells. PMID- 22073008 TI - Bioactive eunicellin-based diterpenoids from the soft coral Cladiella krempfi. AB - Four new eunicellin-based diterpenoids, krempfielins A-D (1-4), along with two known compounds (5 and 6) have been isolated from a soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compounds 5 and 6 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 2, 3, 5 and 6 were shown to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. PMID- 22073007 TI - Anti-biofilm compounds derived from marine sponges. AB - Bacterial biofilms are surface-attached communities of microorganisms that are protected by an extracellular matrix of biomolecules. In the biofilm state, bacteria are significantly more resistant to external assault, including attack by antibiotics. In their native environment, bacterial biofilms underpin costly biofouling that wreaks havoc on shipping, utilities, and offshore industry. Within a host environment, they are insensitive to antiseptics and basic host immune responses. It is estimated that up to 80% of all microbial infections are biofilm-based. Biofilm infections of indwelling medical devices are of particular concern, since once the device is colonized, infection is almost impossible to eliminate. Given the prominence of biofilms in infectious diseases, there is a notable effort towards developing small, synthetically available molecules that will modulate bacterial biofilm development and maintenance. Here, we highlight the development of small molecules that inhibit and/or disperse bacterial biofilms specifically through non-microbicidal mechanisms. Importantly, we discuss several sets of compounds derived from marine sponges that we are developing in our labs to address the persistent biofilm problem. We will discuss: discovery/synthesis of natural products and their analogues-including our marine sponge-derived compounds and initial adjuvant activity and toxicological screening of our novel anti-biofilm compounds. PMID- 22073009 TI - The chemical synthesis of tetrodoxin: an ongoing quest. AB - This contribution reviews all the synthetic work on tetrodotoxin that has appeared in the literature through June 2011. PMID- 22073010 TI - Vasorelaxation, induced by Dictyota pulchella (Dictyotaceae), a brown alga, is mediated via inhibition of calcium influx in rats. AB - This study aimed to investigate the cardiovascular effects elicited by Dictyota pulchella, a brown alga, using in vivo and in vitro approaches. In normotensive conscious rats, CH(2)Cl(2)/MeOH Extract (CME, 5, 10, 20 and 40 mg/kg) from Dictyota pulchella produced dose-dependent hypotension (-4 +/- 1; -8 +/- 2; -53 +/- 8 and -63 +/- 3 mmHg) and bradycardia (-8 +/- 6; -17 +/- 11; -257 +/- 36 and 285 +/- 27 b.p.m.). In addition, CME and Hexane/EtOAc Phase (HEP) (0.01-300 MUg/mL) from Dictyota pulchella induced a concentration-dependent relaxation in phenylephrine (Phe, 1 MUM)-pre-contracted mesenteric artery rings. The vasorelaxant effect was not modified by the removal of the vascular endothelium or pre-incubation with KCl (20 mM), tetraethylammonium (TEA, 3 mM) or tromboxane A(2) agonist U-46619 (100 nM). Furthermore, CME and HEP reversed CaCl(2)-induced vascular contractions. These results suggest that both CME and HEP act on the voltage-operated calcium channel in order to produce vasorelaxation. In addition, CME induced vasodilatation after the vessels have been pre-contracted with L-type Ca(2+) channel agonist (Bay K 8644, 200 nM). Taken together, our data show that CME induces hypotension and bradycardia in vivo and that both CME and HEP induce endothelium-independent vasodilatation in vitro that seems to involve the inhibition of the Ca(2+) influx through blockade of voltage-operated calcium channels. PMID- 22073011 TI - Antibacterial activity of marine and black band disease cyanobacteria against coral-associated bacteria. AB - Black band disease (BBD) of corals is a cyanobacteria-dominated polymicrobial disease that contains diverse populations of heterotrophic bacteria. It is one of the most destructive of coral diseases and is found globally on tropical and sub tropical reefs. We assessed ten strains of BBD cyanobacteria, and ten strains of cyanobacteria isolated from other marine sources, for their antibacterial effect on growth of heterotrophic bacteria isolated from BBD, from the surface mucopolysaccharide layer (SML) of healthy corals, and three known bacterial coral pathogens. Assays were conducted using two methods: co-cultivation of cyanobacterial and bacterial isolates, and exposure of test bacteria to (hydrophilic and lipophilic) cyanobacterial cell extracts. During co-cultivation, 15 of the 20 cyanobacterial strains tested had antibacterial activity against at least one of the test bacterial strains. Inhibition was significantly higher for BBD cyanobacteria when compared to other marine cyanobacteria. Lipophilic extracts were more active than co-cultivation (extracts of 18 of the 20 strains were active) while hydrophilic extracts had very limited activity. In some cases co-cultivation resulted in stimulation of BBD and SML bacterial growth. Our results suggest that BBD cyanobacteria are involved in structuring the complex polymicrobial BBD microbial community by production of antimicrobial compounds. PMID- 22073012 TI - Important determinants for fucoidan bioactivity: a critical review of structure function relations and extraction methods for fucose-containing sulfated polysaccharides from brown seaweeds. AB - Seaweeds--or marine macroalgae--notably brown seaweeds in the class Phaeophyceae, contain fucoidan. Fucoidan designates a group of certain fucose-containing sulfated polysaccharides (FCSPs) that have a backbone built of (1->3)-linked alpha-L-fucopyranosyl or of alternating (1->3)- and (1->4)-linked alpha-L fucopyranosyl residues, but also include sulfated galactofucans with backbones built of (1->6)-beta-D-galacto- and/or (1->2)-beta-D-mannopyranosyl units with fucose or fuco-oligosaccharide branching, and/or glucuronic acid, xylose or glucose substitutions. These FCSPs offer several potentially beneficial bioactive functions for humans. The bioactive properties may vary depending on the source of seaweed, the compositional and structural traits, the content (charge density), distribution, and bonding of the sulfate substitutions, and the purity of the FCSP product. The preservation of the structural integrity of the FCSP molecules essentially depends on the extraction methodology which has a crucial, but partly overlooked, significance for obtaining the relevant structural features required for specific biological activities and for elucidating structure-function relations. The aim of this review is to provide information on the most recent developments in the chemistry of fucoidan/FCSPs emphasizing the significance of different extraction techniques for the structural composition and biological activity with particular focus on sulfate groups. PMID- 22073013 TI - Kinase inhibitors from marine sponges. AB - Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included. PMID- 22073014 TI - Oleic acid produced by a marine Vibrio spp. acts as an anti-Vibrio parahaemolyticus agent. AB - It is known that some strains of Vibrio parahaemolyticus are responsible for gastroenteric diseases caused by the ingestion of marine organisms contaminated with these bacterial strains. Organic products that show inhibitory activity on the growth of the pathogenic V. parahaemolyticus were extracted from a Vibrio native in the north of Chile. The inhibitory organic products were isolated by reverse phase chromatography and permeation by Sephadex LH20, and were characterized by spectroscopic and spectrometric techniques. The results showed that the prevailing active product is oleic acid, which was compared with standards by gas chromatography and high-performance liquid chromatography (HPLC). These active products might be useful for controlling the proliferation of pathogenic clones of V. parahaemolyticus. PMID- 22073015 TI - Identification of occupational cancer risks in British Columbia, Canada: a population-based case-control study of 1,155 cases of colon cancer. AB - OBJECTIVE: Cancer has been recognized to have environmental origin, but occupational cancer risk studies have not been fully documented. The objective of this paper was to identify occupations and industries with elevated colon cancer risk based on lifetime occupational histories collected from 15,463 incident cancer cases. METHOD: A group matched case-control design was used. All cases were diagnosed with histologically proven colon cancers, with cancer controls being all other cancer sites, excluding rectum, lung and unknown primary, diagnosed at the same period of time from the British Columbia Cancer Registry. Data analyses were done on all 597 Canadian standard occupation titles and 1,104 standard industry titles using conditional logistic regression for matched data sets and the likelihood ratio test. RESULTS: Excess colon cancer risks was observed in a number of occupations and industries, particularly those with low physical activity and those involving exposure to asbestos, wood dusts, engine exhaust and diesel engine emissions, and ammonia. DISCUSSION: The results of our study are in line with those from the literature and further suggest that exposure to wood dusts and to ammonia may carry an increased occupational risk of colon cancer. PMID- 22073016 TI - Detection of pesticides in active and depopulated beehives in Uruguay. AB - The influence of insecticides commonly used for agricultural purposes on beehive depopulation in Uruguay was investigated. Honeycombs, bees, honey and propolis from depopulated hives were analyzed for pesticide residues, whereas from active beehives only honey and propolis were evaluated. A total of 37 samples were analyzed, representing 14,800 beehives. In depopulated beehives only imidacloprid and fipronil were detected and in active beehives endosulfan, coumaphos, cypermethrin, ethion and chlorpyrifos were found. Coumaphos was present in the highest concentrations, around 1,000 MUg/kg, in all the propolis samples from active beehives. Regarding depopulated beehives, the mean levels of imidacloprid found in honeycomb (377 MUg/kg, Standard Deviation: 118) and propolis (60 MUg/kg, Standard Deviation: 57) are higher than those described to produce bee disorientation and fipronil levels detected in bees (150 and 170 MUg/kg) are toxic per se. The other insecticides found can affect the global fitness of the bees causing weakness and a decrease in their overall productivity. These preliminary results suggest that bees exposed to pesticides or its residues can lead them in different ways to the beehive. PMID- 22073017 TI - Overweight and obesity and associated factors among school-aged adolescents in Ghana and Uganda. AB - The aim of this study was to assess overweight and obesity and associated factors in school-going adolescents in low income African countries (Ghana, Uganda). The total sample included 5,613 school children aged 13 to 15 years from nationally representative samples from two African countries. Bivariate and multivariable analyses were conducted to assess the relationship between dietary behavior, substance use, physical activity, psychosocial factors and overweight or obesity. The prevalence of overweight and obesity was determined based on self-reported height and weight and the international child body mass index standards. Results indicate a prevalence of overweight or obesity of 10.4% among girls and 3.2% among boys, and 0.9% and 0.5% obesity only among girls and boys, respectively. Among girls smoking cigarettes and loneliness and among boys smoking cigarettes were found to be associated with overweight or obesity in multivariable analysis. Overweight status was not associated with the intake of fruits, vegetables, and sedentary behavior. Low prevalence rates of overweight or obesity were found in Ghana and Uganda. Smoking cessation and social programs could be integrated into strategies to prevent and treat overweight and obesity in youth. PMID- 22073018 TI - Quit attempt correlates among smokers by race/ethnicity. AB - INTRODUCTION: Cigarette smoking is the leading preventable cause of premature deaths in the U.S., accounting for approximately 443,000 deaths annually. Although smoking prevalence in recent decades has declined substantially among all racial/ethnic groups, disparities in smoking-related behaviors among racial/ethnic groups continue to exist. Two of the goals of Healthy People 2020 are to reduce smoking prevalence among adults to 12% or less and to increase smoking cessation attempts by adult smokers from 41% to 80%. Our study assesses whether correlates of quit attempts vary by race/ethnicity among adult (>= 18 years) smokers in the U.S. Understanding racial/ethnic differences in how both internal and external factors affect quit attempts is important for targeting smoking-cessation interventions to decrease tobacco-use disparities. METHODS: We used 2003 Tobacco Use Supplement to the Current Population Survey (CPS) data from 16,213 adults to examine whether the relationship between demographic characteristics, smoking behaviors, smoking policies and having made a quit attempt in the past year varied by race/ethnicity. RESULTS: Hispanics and persons of multiple races were more likely to have made a quit attempt than whites. Overall, younger individuals and those with >high school education, who smoked fewer cigarettes per day and had smoked for fewer years were more likely to have made a quit attempt. Having a smoke-free home, receiving a doctor's advice to quit, smoking menthol cigarettes and having a greater time to when you smoked your first cigarette of the day were also associated with having made a quit attempt. The relationship between these four variables and quit attempts varied by race/ethnicity; most notably receiving a doctor's advice was not related to quit attempts among Asian American/Pacific Islanders and menthol use among whites was associated with a lower prevalence of quit attempts while black menthol users were more likely to have made a quit attempt than white non-menthol users. CONCLUSIONS: Most correlates of quit attempts were similar across all racial/ethnic groups. Therefore population-based comprehensive tobacco control programs that increase quit attempts and successful cessation among all racial/ethnic groups should be continued and expanded. Additional strategies may be needed to encourage quit attempts among less educated, older, and more addicted smokers. PMID- 22073020 TI - Family dysfunction differentially affects alcohol and methamphetamine dependence: a view from the Addiction Severity Index in Japan. AB - We investigated the differential influence of family dysfunction on alcohol and methamphetamine dependence in Japan using the Addiction Severity Index (ASI), a useful instrument that multilaterally measures the severity of substance dependence. The participants in this study were 321 male patients with alcohol dependence and 68 male patients with methamphetamine dependence. We conducted semi-structured interviews with each patient using the ASI, which is designed to assess problem severity in seven functional domains: Medical, Employment/Support, Alcohol use, Drug use, Legal, Family/Social relationships, and Psychiatric. In patients with alcohol dependence, bad relationships with parents, brothers and sisters, and friends in their lives were related to current severe psychiatric problems. Bad relationships with brothers and sisters and partners in their lives were related to current severe employment/support problems, and bad relationships with partners in their lives were related to current severe family/social problems. The current severity of psychiatric problems was related to the current severity of drug use and family/social problems in patients with alcohol dependence. Patients with methamphetamine dependence had difficulty developing good relationships with their father. Furthermore, the current severity of psychiatric problems was related to the current severity of medical, employment/support, and family/social problems in patients with methamphetamine dependence. The results of this study suggest that family dysfunction differentially affects alcohol and methamphetamine dependence. Additionally, family relationships may be particularly related to psychiatric problems in these patients, although the ASI was developed to independently evaluate each of seven problem areas. PMID- 22073019 TI - Is neurodegenerative disease a long-latency response to early-life genotoxin exposure? AB - Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex, a disappearing neurodegenerative disease linked to use of the neurotoxic cycad plant for food and/or medicine, is intensively studied because the neuropathology (tauopathy) is similar to that of Alzheimer's disease. Cycads contain neurotoxic and genotoxic principles, notably cycasin and methylazoxymethanol, the latter sharing chemical relations with nitrosamines, which are derived from nitrates and nitrites in preserved meats and fertilizers, and also used in the rubber and leather industries. This review includes new data that influence understanding of the neurobiological actions of cycad and related genotoxins and the putative mechanisms by which they might trigger neurodegenerative disease. PMID- 22073021 TI - Internet pathways in suicidality: a review of the evidence. AB - The general aim of this study was to review the scientific literature concerning the Internet and suicidality and to examine the different pathways by which suicidal risks and prevention efforts are facilitated through the Internet. An online literature search was conducted using the MEDLINE and Google Scholar databases. The main themes that were investigated included pathological Internet use and suicidality, pro-suicide websites, suicide pacts on the Internet, and suicide prevention via the Internet. Articles were screened based on the titles and abstracts reporting on the themes of interest. Thereafter, articles were selected based on scientific relevance of the study, and included for full text assessment. The results illustrated that specific Internet pathways increased the risk for suicidal behaviours, particularly in adolescents and young people. Several studies found significant correlations between pathological Internet use and suicidal ideation and non-suicidal self-injury. Pro-suicide websites and online suicide pacts were observed as high-risk factors for facilitating suicidal behaviours, particularly among isolated and susceptible individuals. Conversely, the evidence also showed that the Internet could be an effective tool for suicide prevention, especially for socially-isolated and vulnerable individuals, who might otherwise be unreachable. It is this paradox that accentuates the need for further research in this field. PMID- 22073022 TI - A multilevel analysis of neighbourhood built and social environments and adult self-reported physical activity and body mass index in Ottawa, Canada. AB - Canadian research examining the combined effects of social and built environments on physical activity (PA) and obesity is limited. The purpose of this study was to determine the relationships among built and social environments and PA and overweight/obesity in 85 Ottawa neighbourhoods. Self-reported PA, height and weight were collected from 3,883 adults using the International PA Questionnaire from the 2003-2007 samples of the Rapid Risk Factor Surveillance System. Data on neighbourhood characteristics were obtained from the Ottawa Neighbourhood Study; a large study of neighbourhoods and health in Ottawa. Two-level binomial logistic regression models stratified by sex were used to examine the relationships of environmental and individual variables with PA and overweight/obesity while using survey weights. Results identified that approximately half of the adults were insufficiently active or overweight/obese. Multilevel models identified that for every additional convenience store, men were two times more likely to be physically active (OR = 2.08, 95% CI: 1.72, 2.43) and with every additional specialty food store women were almost two times more likely to be overweight or obese (OR = 1.77, 95% CI: 1.33, 2.20). Higher green space was associated with a reduced likelihood of PA (OR = 0.93, 95% CI: 0.86, 0.99) and increased odds of overweight and obesity in men (OR = 1.10, 95% CI: 1.01, 1.19), and decreased odds of overweight/obesity in women (OR = 0.66, 95% CI: 0.44, 0.89). In men, neighbourhood socioeconomic scores, voting rates and sense of community belonging were all significantly associated with overweight/obesity. Intraclass coefficients were low, but identified that the majority of neighbourhood variation in outcomes was explained by the models. Findings identified that green space, food landscapes and social cohesiveness may play different roles on PA and overweight/obesity in men and women and future prospective studies are needed. PMID- 22073024 TI - Patterns of and motivations for concurrent use of video games and substances. AB - "Behavioral addictions" share biological mechanisms with substance dependence, and "drug interactions" have been observed between certain substances and self reinforcing behaviors. This study examines correlates of patterns of and motivations for playing video games while using or feeling the effects of a substance (concurrent use). Data were drawn from a nationally-representative survey of adult Americans who "regularly" or "occasionally" played video games and had played for at least one hour in the past seven days (n = 3,380). Only recent concurrent users' data were included in analyses (n = 1,196). Independent variables included demographics, substance use frequency and problems, game genre of concurrent use (identified by looking titles up in an industry database), and general game playing variables including problem video game play (PVP), consumer involvement, enjoyment, duration, and frequency of play. Exploratory factor analysis identified the following dimensions underlying patterns of and motivations for concurrent use: pass time or regulate negative emotion, enhance an already enjoyable or positive experience, and use of video games and substances to remediate each other's undesirable effects. Multivariate regression analyses indicated PVP and hours/day of video game play were associated with most patterns/motivations, as were caffeine, tobacco, alcohol, marijuana, and painkiller use problems. This suggests that concurrent use with some regular situational pattern or effect-seeking motivation is part of the addictive process underlying both PVP and substance dependence. Various demographic, game playing, game genre of concurrent use, and substance use variables were associated with specific motivations/patterns, indicating that all are important in understanding concurrent use. PMID- 22073023 TI - Playing video games while using or feeling the effects of substances: associations with substance use problems. AB - This study tested the hypothesis that playing video games while using or feeling the effects of a substance--referred to herein as "concurrent use"-is related to substance use problems after controlling for substance use frequency, video gaming as an enthusiastic hobby, and demographic factors. Data were drawn from a nationally representative online survey of adult video gamers conducted by Knowledge Networks, valid n = 2,885. Problem video game playing behavior was operationalized using Tejeiro Salguero and Bersabe Moran's 2002 problem video game play (PVP) measure, and measures for substance use problems were taken from the National Survey of Drug Use and Health (NSDUH). Separate structural equation modeling analyses were conducted for users of caffeine, tobacco, alcohol, and marijuana. In all four models, concurrent use was directly associated with substance use problems, but not with PVP. Video gaming as an enthusiastic hobby was associated with substance use problems via two indirect paths: through PVP for all substances, and through concurrent use for caffeine, tobacco, and alcohol only. Results illustrate the potential for "drug interaction" between self reinforcing behaviors and addictive substances, with implications for the development of problem use. PMID- 22073025 TI - The lag structure and the general effect of ozone exposure on pediatric respiratory morbidity. AB - Up to now no study has investigated the lag structure of children's respiratory morbidity due to surface ozone. In the present study, we investigate the lag structure and the general effect of surface ozone exposure on children and adolescents' respiratory morbidity using data from a particularly well suited area in southern Europe to assess the health effects of surface ozone. The effects of surface ozone are estimated using the recently developed distributed lag non-linear models, allowing for a relatively long timescale, while controlling for weather effects, a range of other air pollutants, and long and short term patterns. The public health significance of the estimated effects is higher than has been previously reported in the literature, providing evidence contrary to the conjecture that the surface ozone-morbidity association is mainly due to short-term harvesting. In fact, our data analysis reveals that the effects of surface ozone at medium and long timescales (harvesting-resistant) are substantially larger than the effects at shorter timescales (harvesting-prone), a finding that is consistent with all children and adolescents being affected by high surface ozone concentrations, and not just the very frail. PMID- 22073027 TI - Farmer health and adaptive capacity in the face of climate change and variability. Part 1: Health as a contributor to adaptive capacity and as an outcome from pressures coping with climate related adversities. AB - This paper examines the role farmers' health plays as an element of adaptive capacity. The study examines which of twenty aspects of adaptation may be related to overall health outcomes, controlling for demographic and on-farm-factors in health problems. The analysis is based on 3,993 farmers' responses to a national survey of climate risk and adaptation. Hierarchical linear regression modelling was used examine the extent to which, in a multivariate analysis, the use of adaptive practices was predictively associated with self-assessed health, taking into account the farmer's rating of whether their health was a barrier to undertaking farm work. We present two models, one excluding pre-existing health (model 1) and one including pre-existing health (model 2). The first model accounted for 21% of the variance. In this model better health was most strongly predicted by an absence of on-farm risk, greater financial viability, greater debt pressures, younger age and a desire to continue farming. Social capital (trust and reciprocity) was moderately associated with health as was the intention to adopt more sustainable practices. The second model (including the farmers' health as a barrier to undertaking farm work) accounted for 43% of the variance. Better health outcomes were most strongly explained, in order of magnitude, by the absence of pre-existing health problems, greater access to social support, greater financial viability, greater debt pressures, a desire to continue farming and the condition of on-farm resources. Model 2 was a more parsimonious model (only nine predictors, compared with 15 in model 1), and explained twice as much variance in health outcomes. These results suggest that (i) pre-existing health problems are a very important factor to consider when designing adaptation programs and policies and (ii) these problems may mediate or modify the relationship between adaptation and health. PMID- 22073026 TI - Considering the definition of addiction. AB - The definition of addiction is explored. Elements of addiction derived from a literature search that uncovered 52 studies include: (a) engagement in the behavior to achieve appetitive effects, (b) preoccupation with the behavior, (c) temporary satiation, (d) loss of control, and (e) suffering negative consequences. Differences from compulsions are suggested. While there is some debate on what is intended by the elements of addictive behavior, we conclude that these five constituents provide a reasonable understanding of what is intended by the concept. Conceptual challenges for future research are mentioned. PMID- 22073028 TI - Farmer health and adaptive capacity in the face of climate change and variability. Part 2: Contexts, personal attributes and behaviors. AB - This study extends the emerging body of research on farmer adaptation to climate change, by segmenting farmers on the basis of specific attributes (health, values, belief about climate change, sense of responsibility for climate change, desire to change, social, human and financial capitals and farmer demographics) and considering such attributes as critical social aspects of the contextualized capacity to adapt. The segmental analysis was based on a nationally representative sample of 3,993 farmers concerned with farmer adaptation of climate risks. The resulting data were subjected to two-step cluster analysis to identify homogenous groups of farmers based on factors related to climate change adaptation. A three-cluster solution was identified wherein farmers were distinguishable on the basis of belief in climate change, desire for financial assistance and advice, social connectedness, information seeking, and adverse farm conditions. The largest group (Cluster 1: 55%) was characterized by farmers who recognized being affected by drought and drying and who were actively engaged in adaptive practices, despite the fact that they had little income and poor farm resources. One third of these farmers reported that their health was a barrier to sustained activity in farming. Cluster 2 (26%) was characterized by farmers not readily affected by drying, who enjoyed good incomes, good health and better farming conditions. They expressed little desire to adapt. The smallest cluster (Cluster 3: 19%) was also characterized by farmers who recognized that they were affected by drying. However, despite a desire to adapt, they had very little means to do so. They reported the poorest natural resources and the poorest health, despite being younger. The findings suggest that it is the intent to adapt, starting from where people are at, which is a more important indicator of the capacity to work towards sustainable practices than assets tests alone. PMID- 22073029 TI - Clarifying exercise addiction: differential diagnosis, co-occurring disorders, and phases of addiction. AB - This paper sets out to clarify the unique features of exercise addiction. It begins by examining how this addiction can be distinguished from compulsions and impulse control disorders both of which, like an addiction, involve excessive behavior that creates adverse effects. Assessment of exercise addiction also requires that clinicians be attuned to other forms of excessive behavior, especially eating disorders that can co-occur with exercise. Finally in an effort to clarify exercise addiction, this paper uses the four phases of addiction to examine the attributes of exercise that define it as a healthy habit distinct from an addiction. The paper ends with a discussion of the implications of these topics for effective assessment and treatment. PMID- 22073030 TI - Prospective power calculations for the Four Lab study of a multigenerational reproductive/developmental toxicity rodent bioassay using a complex mixture of disinfection by-products in the low-response region. AB - In complex mixture toxicology, there is growing emphasis on testing environmentally representative doses that improve the relevance of results for health risk assessment, but are typically much lower than those used in traditional toxicology studies. Traditional experimental designs with typical sample sizes may have insufficient statistical power to detect effects caused by environmentally relevant doses. Proper study design, with adequate statistical power, is critical to ensuring that experimental results are useful for environmental health risk assessment. Studies with environmentally realistic complex mixtures have practical constraints on sample concentration factor and sample volume as well as the number of animals that can be accommodated. This article describes methodology for calculation of statistical power for non independent observations for a multigenerational rodent reproductive/developmental bioassay. The use of the methodology is illustrated using the U.S. EPA's Four Lab study in which rodents were exposed to chlorinated water concentrates containing complex mixtures of drinking water disinfection by products. Possible experimental designs included two single-block designs and a two-block design. Considering the possible study designs and constraints, a design of two blocks of 100 females with a 40:60 ratio of control:treated animals and a significance level of 0.05 yielded maximum prospective power (~90%) to detect pup weight decreases, while providing the most power to detect increased prenatal loss. PMID- 22073031 TI - Improving public health through access to and utilization of medication assisted treatment. AB - Providing access to and utilization of medication assisted treatment (MAT) for the treatment of opioid abuse and dependence provides an important opportunity to improve public health. Access to health services comprising MAT in the community is fundamental to achieve broad service coverage. The type and placement of the health services comprising MAT and integration with primary medical care including human immunodeficiency virus (HIV) prevention, care and treatment services are optimal for addressing both substance abuse and co-occurring infectious diseases. As an HIV prevention intervention, integrated (same medical record for HIV services and MAT services) MAT with HIV prevention, care and treatment programs provides the best "one stop shopping" approach for health service utilization. Alternatively, MAT, medical and HIV services can be separately managed but co-located to allow convenient utilization of primary care, MAT and HIV services. A third approach is coordinated care and treatment, where primary care, MAT and HIV services are provided at distinct locations and case managers, peer facilitators, or others promote direct service utilization at the various locations. Developing a continuum of care for patients with opioid dependence throughout the stages MAT enhances the public health and Recovery from opioid dependence. As a stigmatized and medical disenfranchised population with multiple medical, psychological and social needs, people who inject drugs and are opioid dependent have difficulty accessing services and navigating medical systems of coordinated care. MAT programs that offer comprehensive services and medical care options can best contribute to improving the health of these individuals thereby enhancing the health of the community. PMID- 22073032 TI - Taste learning and memory: a window on the study of brain aging. AB - Taste aversion learning exhibits advantages for research on memory brain systems and its reorganization throughout life. A review of the effects of aging on taste memory abilities offers a complex picture showing preserved, impaired, and enhanced functions. Some of the age-related changes in taste memory seem to be associated with an altered temporal processing. Longer taste-illness delays can be introduced for acquisition of conditioned taste aversions and the modulation of taste learning by the temporal context is absent in naive old rats. It is suggested that an altered hippocampal function is involved in the peculiar performance of these rats. Evidence is also presented which suggests that hippocampal-dependent taste memory can be reactivated by previous learning experiences in old rats. Results obtained after reversible inactivation of the dorsal Hippocampus by tetrodotoxin (TTX) in old rats support such a view. Therefore, the interaction between the previous experience and acute brain interventions should be taken into account when studying the effect of aging on taste memory. PMID- 22073034 TI - Viral-Reactivated Pneumonia during Mechanical Ventilation: Is There Need for Antiviral Treatment? AB - Respiratory viruses are not a common cause of ventilator-associated pneumonia (VAP). Herpesviridae [Herpes simplex virus (HSV) and cytomegalovirus (CMV)] are detected frequently in the lower respiratory tract of ventilated patients. HSV is detected between days 7 and 14 of invasive mechanical ventilation (IMV); presence of the virus does not necessarily imply pathogenicity, but the association with adverse clinical outcomes supports the hypothesis of a pathogenic role in a variable percentage of patients. Bronchopneumonitis associated with HSV should be considered in patients with prolonged IMV, reactivation with herpetic mucocutaneous lesions and those belonging to a risk population with burn injuries or acute lung injury. Reactivation of CMV is common in critically ill patients and usually occurs between days 14 and 21 in patients with defined risk factors. The potential pathogenic role of CMV seems clear in patients with acute lung injury and persistent respiratory failure in whom there is no isolation of bacterial agent as a cause of VAP. The best diagnostic test is not defined although lung biopsies should be considered in addition to the usual methods before starting specific treatment. The role of mimivirus is uncertain and is yet to be defined, but the serologic evidence of this new virus in the context of VAP appears to be associated with adverse clinical outcomes. PMID- 22073033 TI - Dysregulated mTORC1-Dependent Translational Control: From Brain Disorders to Psychoactive Drugs. AB - In the last decade, a plethora of studies utilizing pharmacological, biochemical, and genetic approaches have shown that precise translational control is required for long-lasting synaptic plasticity and the formation of long-term memory. Moreover, more recent studies indicate that alterations in translational control are a common pathophysiological feature of human neurological disorders, including developmental disorders, neuropsychiatric disorders, and neurodegenerative diseases. Finally, translational control mechanisms are susceptible to modification by psychoactive drugs. Taken together, these findings point to a central role for translational control in the regulation of synaptic function and behavior. PMID- 22073035 TI - Colour-grapheme synesthesia affects binocular vision. AB - In colour-grapheme synesthesia, non-coloured graphemes are perceived as being inherently coloured. In recent years, it is debated whether visual processing of synesthesia-inducing achromatic graphemes is similar to that of chromatic graphemes. Here, we exploit the phenomenon of binocular rivalry in which incompatible images presented dichoptically compete for conscious expression. Importantly, the competition only arises if the two images are sufficiently different; if the difference between the images is small, the images will fuse into a single mixed percept. We show that achromatic digits that induce synesthetic colour percepts increase the incidence of binocular rivalry compared to achromatic non-digits that do not evoke such percepts. That is, compared to achromatically perceived non-digits, synesthesia-inducing digits increase the predominance of binocular rivalry over binocular fusion. This finding shows that the synesthetic colour experience can provide the conditions for promoting binocular rivalry, much like stimulus features that induce rivalry in normal vision. PMID- 22073036 TI - Preschoolers' novel noun extensions: shape in spite of knowing better. AB - We examined the puzzling research findings that when extending novel nouns, preschoolers rely on shape similarity (rather than categorical relations) while in other task contexts (e.g., property induction) they rely on categorical relations. Taking into account research on children's word learning, categorization, and inductive inference we assume that preschoolers have both a shape-based and a category-based word extension strategy available and can switch between these two depending on which information is easily available. To this end, we tested preschoolers on two versions of a novel-noun label extension task. First, we paralleled the standard extension task commonly used by previous research. In this case, as expected, preschoolers predominantly selected same shape items. Second, we supported preschoolers' retrieval of item-related information from memory by asking them simple questions about each item prior to the label extension task. Here, they switched to a category-based strategy, thus, predominantly selecting same-category items. Finally, we revealed that this shape to-category shift is specific to the word learning context as we did not find it in a non-lexical classification task. These findings support our assumption that preschoolers' decision about word extension change in accordance with the availability of information (from task context or by memory retrieval). We conclude by suggesting that preschoolers' noun extensions can be conceptualized within the framework of heuristic decision-making. This provides an ecologically plausible processing account with respect to which information is selected and how this information is integrated to act as a guideline for decision-making when novel words have to be generalized. PMID- 22073037 TI - Variability in proactive and reactive cognitive control processes across the adult lifespan. AB - Task-switching paradigms produce a highly consistent age-related increase in mixing cost [longer response time (RT) on repeat trials in mixed-task than single task blocks] but a less consistent age effect on switch cost (longer RT on switch than repeat trials in mixed-task blocks). We use two approaches to examine the adult lifespan trajectory of control processes contributing to mixing cost and switch cost: latent variables derived from an evidence accumulation model of choice, and event-related potentials (ERP) that temporally differentiate proactive (cue-driven) and reactive (target-driven) control processes. Under highly practiced and prepared task conditions, aging was associated with increasing RT mixing cost but reducing RT switch cost. Both effects were largely due to the same cause: an age effect for mixed-repeat trials. In terms of latent variables, increasing age was associated with slower non-decision processes, slower rate of evidence accumulation about the target, and higher response criterion. Age effects on mixing costs were evident only on response criterion, the amount of evidence required to trigger a decision, whereas age effects on switch cost were present for all three latent variables. ERPs showed age-related increases in preparation for mixed-repeat trials, anticipatory attention, and post-target interference. Cue-locked ERPs that are linked to proactive control were associated with early emergence of age differences in response criterion. These results are consistent with age effects on strategic processes controlling decision caution. Consistent with an age-related decline in cognitive flexibility, younger adults flexibly adjusted response criterion from trial-to trial on mixed-task blocks, whereas older adults maintained a high criterion for all trials. PMID- 22073038 TI - Single-trial analyses: why bother? PMID- 22073039 TI - Short-time scale dynamics in the responses to multiple stimuli in visual cortex. AB - Many previous studies have used the presentation of multiple stimuli in the receptive fields (RFs) of visual cortical neurons to explore how neurons might operate on multiple inputs. Most of these experiments have used two fixed stimulus locations within the RF of each neuron. Here the effects of using different positions within the RF of a neuron were explored. The stimuli were presented singly at one of six locations, and also at 15 pair-wise combinations, for 24 V2 cortical neurons in two macaque monkeys. There was considerable variability in how pairs of stimuli interacted within the receptive field of any given neuron: changing the position of the stimuli could result in enhancement, winner-take-all, or suppression relative to the strongest response to a stimulus presented by itself. Across the population of neurons there was no correlation between response strength and response latency. However, for many stimulus pairs the response latency was tightly locked to the shortest response latency of any single stimulus presented by itself independent of changes in response magnitude. In other words, a stimulus that by itself elicited a relatively long latency response, would often affect the magnitude of the response to a pair of stimuli, but not change the latency. These results may provide constraints on the development of models of cortical information processing. PMID- 22073040 TI - ClubSub-P: Cluster-Based Subcellular Localization Prediction for Gram-Negative Bacteria and Archaea. AB - The subcellular localization (SCL) of proteins provides important clues to their function in a cell. In our efforts to predict useful vaccine targets against Gram negative bacteria, we noticed that misannotated start codons frequently lead to wrongly assigned SCLs. This and other problems in SCL prediction, such as the relatively high false-positive and false-negative rates of some tools, can be avoided by applying multiple prediction tools to groups of homologous proteins. Here we present ClubSub-P, an online database that combines existing SCL prediction tools into a consensus pipeline from more than 600 proteomes of fully sequenced microorganisms. On top of the consensus prediction at the level of single sequences, the tool uses clusters of homologous proteins from Gram negative bacteria and from Archaea to eliminate false-positive and false-negative predictions. ClubSub-P can assign the SCL of proteins from Gram-negative bacteria and Archaea with high precision. The database is searchable, and can easily be expanded using either new bacterial genomes or new prediction tools as they become available. This will further improve the performance of the SCL prediction, as well as the detection of misannotated start codons and other annotation errors. ClubSub-P is available online at http://toolkit.tuebingen.mpg.de/clubsubp/ PMID- 22073042 TI - A qualitative engineering analysis of occlusion effects on mandibular fracture repair mechanics. AB - Objectives. The purpose of this analytical study was to examine and critique the engineering foundations of commonly accepted biomechanical principles of mandible fracture repair. Materials and Methods. Basic principles of static equilibrium were applied to intact and plated mandibles, but instead of the traditional lever forces, the mandibles were subjected to more realistic occlusal forces. Results. These loading conditions produced stress distributions within the intact mandible that were very different and more complex than the customary lever-based gradient. The analyses also demonstrated the entirely different mechanical environments within intact and plated mandibles. Conclusions. Because the loading and geometry of the lever-idealized mandible is incomplete, the associated widely accepted bone stress distribution (tension on top and compression on the bottom) should not be assumed. Furthermore, the stress gradients within the bone of an intact mandible should not be extrapolated to the mechanical environment within the plated regions of a fractured mandible. PMID- 22073041 TI - Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli. AB - A member of the attaching and effacing (AE) family of pathogens, enterohemorrhagic Escherichia coli (EHEC) induces dramatic changes to the intestinal cell cytoskeleton, including effacement of microvilli. Effacement by the related pathogen enteropathogenic E. coli (EPEC) requires the activity of the Ca(+2)-dependent host protease, calpain, which participates in a variety of cellular processes, including cell adhesion and motility. We found that EHEC infection results in an increase in epithelial (CaCo-2a) cell calpain activity and that EHEC-induced microvillar effacement was blocked by ectopic expression of calpastatin, an endogenous calpain inhibitor, or by pretreatment of intestinal cells with a cell-penetrating version of calpastatin. In addition, ezrin, a known calpain substrate that links the plasma membrane to axial actin filaments in microvilli, was cleaved in a calpain-dependent manner during EHEC infection and lost from its normal locale within microvilli. Calpain may be a central conduit through which EHEC and other AE pathogens induce enterocyte cytoskeletal remodeling and exert their pathogenic effects. PMID- 22073043 TI - Environmental and occupational health disorders. PMID- 22073045 TI - Toxicological assessment of noxious inhalants. AB - In the past centuries mankind has been exposed to various forms of air pollution not only at his occupational but also in his social environment. He mainly gets exposed with these pollutants through the respiratory organs and partially absorbs them into the body. Many of these airborne substances can be harmful for humans and some of them may account for tumorigenic effects.The following essay describes the main features of toxicological assessment of inhalative environmental and workplace xenobiotics. The essay also explains relevant characteristics and limit values of noxious compounds and gases and depicts modern testing methods. To this end, emphasis is given on methods characterizing the different stages of tumorigenic processes. Various test systems have been developed which can be used in vivo, ex vivo or in vitro. They are to a great part based on the evidence of changes in DNA or particular genes of cells. Among others they have highlighted the impact of interindividual variability on enzymatic activation of xenobiotics and on susceptibility of the host to tumor diseases.Unfortunately, for many inhalative environmental noxious agents no sufficient risk profiles have been developed. The completion of these profiles should be the goal of toxicological assessment in order to allow reasonable socioeconomic or individual-based risk reduction. PMID- 22073044 TI - Cellular and molecular mechanisms in environmental and occupational inhalation toxicology. AB - The central issue of this review are inflammatory changes that take place in the mucous membranes of the respiratory tract as a result of inhaled pollutants. Of particular relevance are dusts, SO(2), ozone, aldehydes und volatile organic compounds. Bioorganic pollutants, especially fragments of bacteria and fungi, occur predominantly in indoor dusts. They activate the toll-like/IL-1 receptor and lead to the activation of the transcription factor NF-kappaB for the release of numerous proinflammatory cytokines. Metals are predominant in ambient air dust particles. They induce the release of reactive oxygen species that cause damage to lipids, proteins and the DNA of the cell. As well as NF-kappaB, transcription factors that foster proliferation are activated via stress activated protein kinases. Organic compounds such as polycyclic aromatic hydrocarbons and nitroso compounds of incomplete combustion processes activate additional via the cytosolic arylhydrocarbon receptor for detoxification enzymes. Sulphur dioxide leads to acid stress, and ozone to oxidative stress of the cell. This is accompanied by the release of proinflammatory cytokines via stress activated protein kinases. Aldehydes and volatile organic compounds activate the vanilloid receptor of trigeminal nerve fibres and induce a hyperreactivity of the mucous membrane via the release of nerve growth factors. The mechanisms described work synergistically and lead to a chronic inflammatory reaction of the mucous membranes of the upper respiratory tract that is regularly demonstrable in inhabitants of western industrial nations. It is unclear whether we are dealing here with a physiological inflammation or with an at least partially avoidable result of chronic pollutant exposure. PMID- 22073047 TI - Multiple Chemical Sensitivity (MCS) - Scientific and Public-Health Aspects. AB - Multiple Chemical Sensitivity (MCS) is a phenomenon which the ENT-doctor should be familiar with. It has its roots in the description of a syndrome in 1987. A worker spilled chemicals at his workplace and from then on he reacted highly sensitive to chemicals. Today, there are many people who explain their complaints with self-suspected MCS. Various pathopysiological models have been proposed, including toxicological, immunological or behaviorial models. But no-one could be proved so far. Since controlled provocation tests have also provided unclear results, an increasing number of doctors assumes today, that MCS reflects a psychic condition. In 1996, an expert team of the WHO has suggested the renaming of MCS to "idiopathic environmental illness" (IEI). However, other doctors still assume a chemical cause. Since there are neither straightforward diagnostic methods to proof MCS, nor reliable therapeutic concepts, treatment of MCS patients is usually difficult. The MCS-debate (somatic vs psychic causes) seems to reflect the dilemma of the medical profession today, that somatic disorders of known origin can be well treated, whereas the increasing number of psychosomatic/ somatoform disorders is often resistant to medical help. The ENT-doctor should pay attention to changes of the nasal mucous membrane, nasal resistance and the sense of smell. Moreover he should know about the peculiarities of MCS-patients. The manuscript describes the present knowledge and state of discussion with special regard to the situation in Germany. PMID- 22073046 TI - Actual therapeutic management of allergic and hyperreactive nasal disorders. AB - Allergic rhinitis (AR) and hyperractive disorders of the upper airways, depending upon the type of releasing stimuli, are defined as nasal hyperreactivity, for example in the case of AR, or as non-specific nasal hyperreactivity and as idiopathic rhinitis (IR) (synonyms frequently used in the past: non-specific nasal hyperreactivity; vasomotor rhinitis) in the case of non-characterised stimuli.An early and professional therapy of allergic disorders of the upper airways is of immense importance as allergic rhinitis is detected in comorbidities such as asthma and rhino sinusitis. The therapeutic concept is influenced by new and further developments in pharmacological substance classes such as antihistamines and glucocorticosteroids. Specific immune therapy, the only causal therapy for AR, has been reviewed over the past few years in respect of the type and pattern of application. However, to date no firm recommendations on oral, sublingual and /or nasal immune therapy have yet been drawn up based on investigations of these modifications.Therapeutic management of IR is aimed at a symptom-oriented therapy of nasal hyperactivity as etiological factors relating to this form of rhinitis are not yet sufficiently known. Drug groups such as mast cell stabilizers, systemic and topic antihistamines, topic and systemic glucocorticosteroids, ipatroium bromide and alpha symphatomimetics belong to the spectrum of the therapeutics employed. PMID- 22073048 TI - Current aspects of hearing loss from occupational and leisure noise. AB - Hearing loss from occupational and leisure noise numbers amongst the most frequent causes of an acquired sensorineural hearing loss. Here we present a review of up-to-date findings on the pathophysiology of acoustic injury to the inner ear, with special attention being paid to its molecular-biological and genetic aspects. Epidemiological aspects shall also be dealt with, as shall the roles of lacking recovery from occupational noise due to additional exposure by leisure noise and the combined exposure of noise and chemicals. Based on the epidemiological and pathophysiological findings and against the background of published animal-experimental, pre-clinical and clinical findings, the various approaches for prevention, protection and therapeutic intervention with acoustic trauma are discussed. Pharmacological strategies involving anti-oxidative, anti excitotoxic and anti-apoptotic substances as well as non-pharmacological strategies like "sound conditioning" are given attention. Furthermore, systemic and local substance application as well as the therapy of acute acoustic trauma and chronic hearing problems (including modern therapy forms for comorbidities such as tinnitus) shall be delved into. PMID- 22073050 TI - Reconstructive methods in hearing disorders - surgical methods. AB - Restoration of hearing is associated in many cases with resocialisation of those affected and therefore occupies an important place in a society where communication is becoming ever faster. Not all problems can be solved surgically. Even 50 years after the introduction of tympanoplasty, the hearing results are unsatisfactory and often do not reach the threshold for social hearing. The cause of this can in most cases be regarded as incomplete restoration of the mucosal function of the middle ear and tube, which leads to ventilation disorders of the ear and does not allow real vibration of the reconstructed middle ear. However, a few are also caused by the biomechanics of the reconstructed ossicular chain. There has been progress in reconstructive middle ear surgery, which applies particularly to the development of implants. Implants made of titanium, which are distinguished by outstanding biocompatibility, delicate design and by biomechanical possibilities in the reconstruction of chain function, can be regarded as a new generation. Metal implants for the first time allow a controlled close fit with the remainder of the chain and integration of micromechanical functions in the implant. Moreover, there has also been progress in microsurgery itself. This applies particularly to the operative procedures for auditory canal atresia, the restoration of the tympanic membrane and the coupling of implants. This paper gives a summary of the current state of reconstructive microsurgery paying attention to the acousto-mechanical rules. PMID- 22073051 TI - Restoration of hearing by hearing aids: conventional hearing aids - implantable hearing aids - cochlear implants - auditory brainstem implants. AB - Aim of this report is to explain the current concept of hearing restoration using hearing aids. At present the main issues of conventional hearing aids are the relative benefits of analogue versus digital devices and different strategies for the improvement of hearing in noise. Implantable hearing aids provide a better sound quality and less distortion. The lack of directional microphones is the major disadvantage of the partially implantable hearing aids commercially available. Two different clinical studies about fully implantable hearing aids have been started in 2004. One of the most-promising developments seems to be the electric-acoustic stimulation. PMID- 22073049 TI - Therapy of hearing disorders - conservative procedures. AB - A wide range of therapeutic strategies are available for the therapy of hearing disorders including pharmaceutical, acoustic, electrical, surgical, radiological, cognitive-behavioural and so-called "alternative" strategies. This review focuses on general conservative strategies and specific therapeutic approaches mainly for inner ear disorders, whereas surgical and device-based therapies including hearing aids and cochlear implants are described in other chapters in this volume.In addition to the systemic medication-based therapies for the treatment of hearing disorders, the rapidly growing field of local drug delivery to the inner ear as a promising therapeutic strategy is discussed on the background of unresolved issues. After description of non-drug-based therapeutic procedures, the conservative therapy of specific diseases and syndromes is reviewed.In general, there is a major discrepancy between promising animal studies up to regeneration and stem-cell transplantation, and uncontrolled experimental studies in humans on the one hand and the shortage of randomized controlled clinical trials with a high level of evidence on the other hand. Therefore, the review and comments on published clinical studies should assist the reader in making his/her own decision about the effectiveness of various, especially pharmaceutical treatments. From a critical analysis - particularly of the clinical studies presented - conclusions are drawn for the therapy of hearing disorders in the future. PMID- 22073052 TI - Technical devices for hearing-impaired individuals: cochlear implants and brain stem implants - developments of the last decade. AB - Over the past two decades, the fascinating possibilities of cochlear implants for congenitally deaf or deafened children and adults developed tremendously and created a rapidly developing interdisciplinary research field.The main advancements of cochlear implantation in the past decade are marked by significant improvement of hearing and speech understanding in CI users. These improvements are attributed to the enhancement of speech coding strategies.The Implantation of more (and increasingly younger) children as well as the possibilities of the restoration of binaural hearing abilities with cochlear implants reflect the high standards reached by this development. Despite this progress, modern cochlear implants do not yet enable normal speech understanding, not even for the best patients. In particular speech understanding in noise remains problematic [1]. Until the mid 1990ies research concentrated on unilateral implantation. Remarkable and effective improvements have been made with bilateral implantation since 1996. Nowadays an increasing numbers of patients enjoy these benefits. PMID- 22073054 TI - Re-establishment of olfactory and taste functions. AB - The incidence of olfactory disorders is appoximately 1-2% and they can seriously impact on the quality of life. Quantitative disorders (hyposmia, anosmia) are distinguished from qualitative disorders (parosmia, phantosmia). Olfactory disorders are classified according to the etiology and therapy is planned according to the underlying pathophysiology. In ENT patients olfactory disorders caused by sinonasal diseases are the most common ones, followed by postviral disorders. Therapy consists of topical and systemic steroids, whereas systemic application seems to be of greater value. It is very difficult to predict the improvement of olfactory function using surgery, moreover, the long term - success in surgery is questionable. Isolated taste disorders are rare and in most often caused by underlying diseases or side effects of medications. A meticulous history is necessary and helps to choose effective treatment. In selected cases zinc might be useful. PMID- 22073053 TI - Procedures for restoring vestibular disorders. AB - This paper will discuss therapeutic possibilities for disorders of the vestibular organs and the neurons involved, which confront ENT clinicians in everyday practice. Treatment of such disorders can be tackled either symptomatically or causally. The possible strategies for restoring the body's vestibular sense, visual function and co-ordination include medication, as well as physical and surgical procedures. Prophylactic or preventive measures are possible in some disorders which involve vertigo (bilateral vestibulopathy, kinetosis, height vertigo, vestibular disorders when diving (Tables 1 (Tab. 1) and 2 (Tab. 2)). Glucocorticoid and training therapy encourage the compensation of unilateral vestibular loss. In the case of a bilateral vestibular loss, it is important to treat the underlying disease (e.g. Cogan's disease). Although balance training does improve the patient's sense of balance, it will not restore it completely.In the case of Meniere's disease, there are a number of medications available to either treat bouts or to act as a prophylactic (e.g. dimenhydrinate or betahistine). In addition, there are non-ablative (sacculotomy) as well as ablative surgical procedures (e.g. labyrinthectomy, neurectomy of the vestibular nerve). In everyday practice, it has become common to proceed with low risk therapies initially. The physical treatment of mild postural vertigo can be carried out quickly and easily in outpatients (repositioning or liberatory maneuvers). In very rare cases it may be necessary to carry out a semicircular canal occlusion.Isolated disturbances of the otolith function or an involvement of the otolith can be found in roughly 50% of labyrinth disturbances. A specific surgical procedure to selectively block the otolith organs is currently being studied. When an external perilymph fistula involving loss of perilymph is suspected, an exploratory tympanotomy involving also the round and oval window niches must be carried out. A traumatic rupture of the round window membrane can, for example, also be caused by an implosive inner ear barotrauma during the decompression phase of diving. Dehiscence of the anterior semicircular canal, a relatively rare disorder, can be treated conservatively (avoiding stimuli which cause dizziness), by non-ablative "resurfacing" or by "plugging" the semicircular canal. A perilymph fistula can cause a Tullio-phenomenon resulting from a traumatic dislocation or hypermobility of the stapes, which can be surgically corrected. Vestibular disorders can also result from otosurgical therapy. When balance disorders persist following stapedectomy it is necessary to carry out a revision operation in order to either exclude a perilymph fistula or shorten the piston. Surgically reducing the size of open mastoid cavities (using for example porous hydroxylapatite or cartilage) can result in a reduction of vertiginous symptoms while nursing or during exposure to ambient air. Vestibular disturbances can occur both before and after vestibular nerve surgery (acoustic neuroma). Initially, good vestibular compensation can be expected after surgically removing the acoustic neuroma. An aberrant regeneration of nerve fibers of the vestibulocochlear nerve has been suggested as a cause for secondary worsening. Episodes of vertigo can be caused by an irritation of the vestibular nerve (vascular loop). Neurovascular decompression is generally regarded as the best surgical therapy. In the elderly, vestibular disturbances can severely limit quality of life and are often aggravated by multiple comorbidities. Antivertiginous drugs (e.g. dimenhydrinate) in combination with movement training can significantly reduce symptoms. Administering antivertiginous drugs over varying periods of time (e.g. transdermal scopolamine application via patches) as well as kinetosis training can be used as both prophylactically and as a therapy for kinetosis. Exposure training should be used as a prophylactic for height vertigo. PMID- 22073058 TI - Surgical and conservative methods for restoring impaired motor function - facial nerve, spinal accessory nerve, hypoglossal nerve (not including vagal nerve or swallowing). AB - The present review gives a survey of rehabilitative measures for disorders of the motor function of the mimetic muscles (facial nerve), and muscles innervated by the spinal accessory and hypoglossal nerves. The dysfunction can present either as paralysis or hyperkinesis (hyperkinesia). Conservative and surgical treatment options aimed at restoring normal motor function and correcting the movement disorders are described. Static reanimation techniques are not dealt with. The final section describes the use of botulinum toxin in the therapy of dysphagia. PMID- 22073055 TI - Restorative procedures in disturbed function of the upper airways - nasal breathing. AB - These days, functional rhinosurgery is almost always taken to mean the improvement of nasal airflow. However, air should not only pass through the nose without obstruction. It needs to be warmed, moistened and filtered. This requires sufficient air/mucous membrane contact by spreading airflow over the entire turbinate region, as well as regulation of nasal airway resistance and the degree of turbulence within the nasal cycle. These factors are not considered enough in the concept of functional rhinosurgery.There cannot be a rigid concept for functional/aesthetic rhinosurgery, the surgical procedure must be adapted to the individual anatomy and pathology. In spite of this, it must be clear (based on evidence) which surgical steps can solve a functional problem of the nose in the long term. This paper cannot explain evidence-based treatment strategies to restore nasal respiratory function because in all branches of rhinosurgery, there are no prospective studies available with a sufficiently high sample size and long-term results objectivized by functional diagnosis. Studies available on septal surgery show better results for SP after Cottle than for SMR after Killian. However, the success rate of a 70 to 80% improvement in nasal breathing is not satisfactory. The incidence of postoperative, dry nasal mucosa is also too high. The task of rhinology is to stress the functional side of rhinosurgery more. This includes preoperative analysis of the causes of disturbed respiratory function using the functional diagnosis methods available, the use of evidence based surgical techniques and postoperative, objectivized quality control. More research needs to be done on the physiology and pathophysiology of nasal airflow as well as on the effect of rhinosurgery on airflow. Numerical flow simulation can contribute greatly to this because the effects of shape changes on the flow can be visualized. Methods need to be developed which can be used for routine, diagnostic recording of warming, moistening and filtering of the respiratory air. PMID- 22073056 TI - Reconstructive procedures for disturbed functions within the upper airway: pharyngeal breathing/snoring. AB - Breathing disorders which have their origin within the pharynx mainly occur during sleep. These so-called obstructive sleep-related breathing disorders include three different disturbances which have to be distinguished properly: simple snoring, upper airway resistance syndrome (UARS) and obstructive sleep apnea (OSA). Each disturbance requires a different treatment.Simple snoring does not affect the physical health of the snorer himself, but often leads to social problems due to the annoying character of the breathing sounds. Appropriate treatment modalities are oral devices and transcutaneous or ttransmucosal electrical stimulation of the muscles of the floor of the mouth via surface electrodes. As reconstructive surgical procedures adenotomies, tonsillectomies, tonsillotomies, or adenotonsillectomies are successfully used in children. Moreover, in adults radiofrequency treatments of the tonsils, the soft palate and of the base of tongue, as well as uvulopalatopharyngoplasty (UPPP), laser assisted uvulopalatoplasty (LAUP) and palatal implants are adequate treatments for simple snoring.Adequate therapies for UARS and mild OSA (less than 20 breathing events per hour of sleep) are oral appliances. Nasal continuos positive airway pressure (NCPAP) ventilation is a very successful treatment modality, but shows low compliance in these patients, as daytime symptoms like excessive sleepiness or or impaired cognitive functions are often unincisive in patients with mild OSA. Reconstructive procedures like UPPP, radiofrequency surgery of the tonsils or the base of tongue, hyoid suspension, mandibular osteotomy with genioglossus advancement (MO) are successful treatment options either as isolated procedures or in combination within so-called multi-level surgery concepts.Goldstandard for the treatment of moderate to severe OSA is the nCPAP ventilation. All patients should at least try this treatment modality. Only in the rare cases of nCPAP failure (2%) and in the relatively frequent cases of nCPAP incompliance (30%) reconstructive surgical procedures become necessary as second choice treatments. These are adenectomies, tonsillectomies, tonsillotomies in children and hyoid suspension, MO, multi-level surgery concepts, or maxillomandibular advancement osteotomies in adults. PMID- 22073060 TI - Rehabilitation of the trigeminal nerve. AB - When it comes to restoring impaired neural function by means of surgical reconstruction, sensory nerves have always been in the role of the neglected child when compared with motor nerves. Especially in the head and neck area, with its either sensory, motor or mixed cranial nerves, an impaired sensory function can cause severe medical conditions. When performing surgery in the head and neck area, sustaining neural function must not only be highest priority for motor but also for sensory nerves. In cases with obvious neural damage to sensory nerves, an immediate neural repair, if necessary with neural interposition grafts, is desirable. Also in cases with traumatic trigeminal damage, an immediate neural repair ought to be considered, especially since reconstructive measures at a later time mostly require for interposition grafts.In terms of the trigeminal neuralgia, commonly thought to arise from neurovascular brainstem compression, a pharmaceutical treatment is considered as the state of the art in terms of conservative therapy. A neurovascular decompression of the trigeminal root can be an alternative in some cases when surgical treatment is sought after. Besides the above mentioned therapeutic options, alternative treatments are available. PMID- 22073057 TI - Reconstructive procedures for impaired upper airway function: laryngeal respiration. AB - The larynx is the "bottleneck" of the human airway. For this reason, the effects of stenosing laryngeal pathologies on the vital factor respiratory gas exchange are particularly critical.Internal stabilization is a prerequisite for recovery of the laryngeal respiratory function in severe forms of inspiratory collapse (laryngomalacia). Effective laser surgery techniques have been developed to this end in recent years.Glottis-dilating surgery in cases of bilateral vocal cord motion impairment is now moving in the direction of endoscopic laser cordotomy or cordectomy, whereas arytenoidectomy and open surgical procedures are now used only rarely due to higher secondary morbidity rates. In individual cases, in particular if functional recovery is expected, temporary laterofixation of a vocal cord using an endoscopic suturing technique can be a helpful approach.Extensive laryngeal defects can be covered by means of composite grafts with mucosal lining, a supporting skeleton and their own vascularization. Autologous transplantation of the larynx, with its complex surgical and immunological problems, has become a manageable procedure. The problems of post transplantation reinnervation and risk assessment of immunosuppression-induced recurrence of the tumor are still under consideration.Reanimation of the bilaterally paralyzed larynx by means of neurorrhaphy (neurosuture), neural grafting and, more recently, functional electrostimulation (pacemaker) represents a challenge for the coming years. In most cases of paralysis of the recurrent laryngeal nerve, a part of the muscles is maintained by synkinetic reinnervation when therapy is carried out, which however also prevents effective vocal cord movement due to simultaneous activity of agonists and antagonists. Modulation of reinnervation by means of electrostimulation and modern genetic therapy approaches justify hopes of better outcomes in the future. PMID- 22073061 TI - Conservative approaches to the management of voice disorders. AB - The presence of a voice disorder not only affects social interaction but potentially also has a major impact on the work environment. The latter is becoming more important given the increasing demands employers make in terms of competency in both communication skills and adequacy of phonation. The development of newer and more precise phono-microsurgical techniques for the treatment of an increasing variety of voice disorders has not entirely replaced a conservative approach to voice rehabilitation. Nevertheless, conservative methods have to demonstrate an higher effectiveness in comparison with the microsurgical intervention given the alternative indications. This would be especially true for the more specific and systematically a given individual glottic pathophysiology could be changed in direction of individual phonatory physiology or supplementary phonation mechanism. This desired changing depends not only on the theoretical concepts but also on maintaining strict therapeutic principles during their clinical application. Conservative management of voice disorders has to be intensive and comprehensive, especially in the case of accepting our model of Larnygeal Double Phonation Function and the existence of a phonatory feedback loop. PMID- 22073059 TI - Reconstructive and rehabilitating methods in patients with dysphagia and nutritional disturbances. AB - As diverse as the causes of oropharyngeal dysphagia can be, as broad is the range of potential therapeutical approaches. In the past two decades, methods of plastic-reconstructive surgery, in particular microsurgically revascularised tissue transfer and minimally invasive, endoscopic techniques of every hue have substantially added to the portfolio of reconstructive surgery available for rehabilitating deglutition. Numerically, reconstructing the pharyngolaryngeal tract following resection of squamous-cell carcinomas in the oral cavity, the pharynx and the larynx has been gaining ground, as has functional deglutitive therapy performed to treat posttherapeutical sequelae. Dysphagia and malnutrition are closely interrelated. Every third patient hospitalised in Germany suffers from malnutrition; ENT tumour patients are not excluded. For patients presenting with advancing malnutrition, the mortality, the morbidity and the individual complication rate have all been observed to increase; also a longer duration of stay in hospital has been noted and a lesser individual toleration of treatment, diminished immunocompetence, impaired general physical and psychical condition and, thus, a less favourable prognosis on the whole. Therefore, in oncological patients, the dietotherapy will have to assume a key role in supportive treatment. It is just for patients, who are expected to go through a long process of deglutitive rehabilitation, that enteral nutrition through percutaneous endoscopically controlled gastrostomy (PEG) performed at an early stage can provide useful and efficient support to the therapeutic efforts. Nutrition and oncology are mutually influencing fields where, sooner or later, a change in paradigms will have to take place, i.e. gradually switching from therapy to prevention. While cancer causes malnutrition, feasible changes in feeding and nutrition-associated habits, including habitual drinking and smoking, might lower the incidence of cancer worldwide by 30 to 40% (American Institute of Cancer Research 1999).Esse oportet, ut vivas, non vivere ut edas. / Thou shouldst eat to live, not live to eat.Cicero 106 - 43 B.C. PMID- 22073063 TI - Rehabilitation of impaired speech function (dysarthria, dysglossia). AB - Speech disorders can result (1) from sensorimotor impairments of articulatory movements = dysarthria, or (2) from structural changes of the speech organs, in adults particularly after surgical and radiochemical treatment of tumors = dysglossia. The decrease of intelligibility, a reduced vocal stamina, the stigmatization of a conspicuous voice and manner of speech, the reduction of emotional expressivity all mean greatly diminished quality of life, restricted career opportunities and diminished social contacts. Intensive therapy based on the pathophysiological facts is absolutely essential: Functional exercise therapy plays a central role; according to symptoms and their progression it can be complemented with prosthetic and surgical approaches. In severe cases communicational aids have to be used. All rehabilitation measures have to take account of frequently associated disorders of body motor control and/or impairment of cognition and behaviour. PMID- 22073062 TI - Surgical procedures for voice restoration. AB - Surgical procedures for voice restoration serve to improve oral communication by better vocal function. They comprise of phonomicrosurgery, with direct and indirect access to the larynx; laryngoplasty; laryngeal injections; and surgical laryngeal reinnervation. The basis for modern surgical techniques for voice disorders is the knowledge about the ultrastructure of the vocal folds and the increasing experience of surgeons in voice surgery, while facing high social and professional demands on the voice. Vocal activity limitation and participation restriction has become more important in the artistic and social areas. A number of surgical methods that have been developed worldwide for this reason, are presented in this article. Functional oriented surgery has to meet high standards. The diagnostics of vocal function has to be multi-dimensional in order to determine the indication and the appropriate surgical intervention. PMID- 22073065 TI - Conservative procedures in skin reconstitution. AB - Skin exerts a number of essential protective functions ensuring homeostasis of the whole body. In the present review barrier function of skin and its expression of antimicrobial peptides are discussed. Barrier function is provided by the dynamic stratum corneum structure composed of lipids and corneocytes. Stratum corneum is a conditio sine qua non for terrestrial life. Impairment of barrier function can be due to injury and inflammatory skin diseases. Therapeutic options are discussed with special emphasis of radiodermatitis and irritant contact dermatitis in patients with hearing device. The use of antimicrobial peptides is illustrated by facial inflammatory skin diseases. In wound healing new developments include biotechnological developments of matrix- and growth factors and tissue-engineered skin substitutes. In everyday wound care of chronic wounds the concept of wound bed preparation (TIME) constitutes the base of successful treatment. PMID- 22073064 TI - Restorative procedures in cases of impaired voice function following complete laryngectomy. AB - Surgical voice restoration with a tracheo-oesophageal fistula using an alloplastic voice prosthesis is the current standard in Germany for patients with laryngectomy. With the increasing widespread use of this type of rehabilitation new duties emerge, not only for ones colleagues in the hospital but also for those in general practice. Care of these patients close to their home must be the aim of us all. With the use of voice prostheses on the increase any problems arising for the clinician are few and easily treatable; for these a therapy concept should be borne in mind. Surgical voice restoration is indicated only in individual cases due, among other reasons, to the high operational costs involved. If surgical voice restoration is impossible or unsuccessful, oesophageal voice replacement and electronic voice support are realistic alternatives. Improvements can be expected as regards the durability of voice prostheses, methods of replacing them, and speech procedure with finger-free tracheostomy closure. Greater use of the artificial larynx without tracheostomy is the objective for the distant future. PMID- 22073067 TI - Diagnostic and therapeutic-restorative procedures for masticatory dysfunctions. AB - Temporomandibular disorders (TMD) or craniomandibular disorders, respectively, involve diseases of the teeth and periodontia as well as the masticatory muscles, temporomandibular joints and associated structures. It has been shown in recent years that psychological, social and general medical influences are of enormous importance in the etiology of TMD in addition to anatomical, physiological, parafunctional and other biological causes. This signifies that therapists confronted with TMD should already include at an early stage other specialists such as pain therapists, neurologists, ENT physicians, psychotherapists and physiotherapists. Patients need to be referred to dentists specializing in TMD when ENT examinations yield no pathological findings. The treatment of TMD is subdivided into the following steps that are always related to underlying diagnoses: informing patients, self-observation, relaxation therapy, behavioral therapy, physiotherapy, drug therapy, therapeutic local anesthesia, splint therapy, and, if necessary, prosthetic and/or orthodontic therapy to restore a stable occlusion. PMID- 22073068 TI - Reconstitution of lost cervical spine function: management strategies. AB - The cervical spine (CS) is the most vulnerable part of the whole spine because it has least protection. This is due to its high mobility (few bone, but largely muscle and joint support) which is associated with a high injury risk. The anatomical characteristics are based on evolutionary biological reasons, i.e. humans had to be able to freely controlling the surrounding space with their eyes and to have permanent postural control by an upright position of the head. The cervical spine, its joint and the surrounding muscles are highly interconnected (e.g. direct neuronal projections into the brain stem, connections to the TMJ, Head's zones with projections to the skin surface). Moreover, the spinal pain memory store can lead to a variets of multi-facette clinical pictures. In addition to reversible disorders of the cervical spine, posttraumatic disorders play a major role. The therapy options available include physiotherapy, drug therapy and surgical measures. However, a multidisciplinary approach is most favourable. PMID- 22073066 TI - Operative treatment of functional facial skin disorders. AB - The skin is the principal interface between the body and the surrounding world and thus serves as a protective barrier against trauma, temperature extremes and radiation. With receptors for pressure, movement, heat and cold, it also acts as sensory organ and through sweat secretion plays a role in thermoregulation and electrolyte metabolism. Not all of these functions are relevant to facial skin, however, cosmetic aspects are of vital importance.Disorders primarily affect the protective skin function in defect and scar areas. For operative correction, the following principles should be applied: Minimization of scar development by adherence to indicated incision lines in the face, preferred use of local skin flaps for defect coverage in order to obtain optimal results regarding texture, complexion and sensitivity of skin, as well as consideration of aesthetic units. Recent developments in this field are tissue culture, occlusive dressings, and the use of growth factors. Age-related skin changes with impairment of cosmetic function are characterized by the development of creases and looseness of skin. Rejuvenation has become an important segment of skin surgery. For surface treatment, especially of creases and acne scars, various types of laser treatment are employed. Deeper lines can be filled with filler materials. The integration of the superficial musculoaponeurotic system (SMAS) into face lift procedures has lead to more viable and natural results. Due to protruding tissue, blepharoplasty of the upper lid is often carried out in combination with forehead lift and eyebrow lift procedures.The optimized use of growth factors and synthetic materials, which serve as a matrix, are aimed at skin replacement which mimics the quality and functions of skin as closely as possible. On the whole, however, the reconstruction of defect through local tissue transfer is still considered as the treatment of choice. PMID- 22073069 TI - Therapeutic methods for psychosomatic disorders in oto-rhino-laryngology. AB - Psychosomatic disorders such as tinnitus, acute hearing loss, attacks of dizziness, globus syndrome, dysphagias, voice disorders and many more are quite common in ear, nose and throat medicine. They are mostly caused by a number of factors, although the bio-psycho-social model does play an important role. Initial contact with a psychosomatically ill patient and compiling a first case history are important steps to psychosomatic oriented therapy. This contribution will sum up the most important otorhinolaryngological diseases with psychosomatic comorbidity and scientifically evaluated methods of treatment. The contribution will also introduce the reader to important psychosomatic treatment methods from psychotherapeutic relaxation techniques to talk therapy. To conclude, the contribution will discuss the criteria for outpatient as well as inpatient treatment and look at the advantages of psychosomatically oriented therapy, both for the patient and for the doctor. PMID- 22073070 TI - Respiratory pathophysiology: sleep-related breathing disorders. AB - A widespread network of respiratory-related neurons within the brainstem controls the regular respiratory cycle, which is dependent upon unspecific and specific drives like hypoxia or hypercapnia. This respiratory network and its respiratory drives are subjects to typical changes during the transition from wakefulness to sleep and within the various sleep states, which favor a destabilization of breathing during sleep. There is also a respiratory-related innervation of the dilating and stiffening pharyngeal muscles as well as a local reflex control of the basic tone of upper airway muscles, both of which are influenced by the different states of wakefulness and sleep. These sleep-related changes cause an increase in upper airway resistance during sleep. In healthy subjects, however, these features during sleep are almost completely compensated and the gas exchange is hardly hindered. However, in the case of illness, severe disordered breathing, disturbed gas exchange and interrupted sleep may occur. The central hypoventilation syndrome, central apnea-hypopnea syndromes, as well as the obstructive sleep apnea syndrome belong to these diseases. Because of the intense research, we have a detailed picture of the pathophysiological mechanisms of the origin and the maintenance of sleep-related breathing disorders. PMID- 22073072 TI - The value of oral appliances in the treatment of obstructive sleep apnoea. AB - Oral appliances have long been used to treat snoring and mild to moderate obstructive sleep apnoea. This kind of treatment is considered an alternative, non-invasive treatment option. Mandibular protrusive appliances enlarge and stabilise the oro- and hypo-pharyngeal airway space by advancing the mandible, and stretching the attached soft tissue, in particular the tongue, soft palate, uvula, and the pharyngeal tissues. This article summarises the indications, contraindications, and possible side-effects of using oral appliances. Therapeutic efficacy is influenced by multiple parameters that are clinically difficult to control. One major parameter is the patient's stomatognathic situation of the patient. Thus oral appliances are restricted to patients whose dental retention is adequate for permanent treatment and who do not suffer from temporomandibular joint dysfunction. Regular follow-up sleep studies and dental evaluations are necessary to ensure adequate permanent treatment. PMID- 22073071 TI - Current diagnostic trends in sleep disordered breathing. AB - Over the past two decades, various methods of sophisticated diagnostics of the upper airway have been tested in patients with sleep disordered breathing (SDB). In this context, endoscopic techniques and pharyngeal pressure recordings are of special interest for the otorhinolaryngologist.Whereas the basic otorhinolaryngological examination is able to detect anatomical pathologies which need to and can be corrected, the Muller-Manoeuvre seems to help exclude patients from uvulopalatopharyngoplasty.To a large extent, videoendoscopy during natural sleep has been replaced by videoendoscopy under sedation. Despite good methodological preparation and impressive presentability of the obstructions, there is not sufficent evidence to demonstrate that videoendoscopy under sedation improves the success rate of surgery in SDB. However, in assessing the impact of the epiglottis on upper airway obstructions in the individual patient, videoendoscopy is the only existing option.Multi-channel pressure recordings permit analysing the entire sleep period and are well tolerated. They can be used to determine the Apnea-Hypopnea-Index as well as to quantify obstructive events in the upper and lower pharyngeal segment. On the other hand, obstructions of the tongue base cannot be distinguished from obstructions related to the epiglottis. According to the data available so far, the benefit of sophisticated diagnostics of the upper airway still has to be judged with caution. Therefore, the promising approaches of both videoendoscopy under sedation and multi-channel pressure recordings deserve further intensive research. According to the personal estimation of the author, they will nevertheless become valuable tools for otorhinolaryngologists in the near future, thus complementing the basic ENT examination and improving the treatment of patients. PMID- 22073073 TI - A critical evaluation of surgery for sleep disordered breathing. AB - Surgical strategies for the treatment of sleep disordered breathing, although widespread and frequently used, continue to be a controversial issue. Colleagues who primarily focus on conservative treatment options point to the limitations in the available data and remind us of serious methodological concerns surrounding the current literature for surgical treatment alternatives. In accordance with the principles of evidence based medicine the best available evidence should be used to assess the efficacy of surgical treatment. While placebo-controlled trials are feasible only in selected cases, recent examples of controlled clinical trials demonstrate that well designed prospective studies are indeed possible in the field of surgical treatment. Aim of the presented review is to critically evaluate current knowledge and evidence in this field and to give examples for how to overcome methodological issues in the future. Furthermore it will be demonstrated that even the "gold standard" of conservative treatment still leaves numerous questions open in regard to primary acceptance, long term compliance and surveillance. The assessment of treatment strategies is still based primarily on the effects seen in respiratory surrogate parameters under laboratory conditions. In the future, a broad spectrum of subjective and long term objective parameters such as cardiovascular mortality needs to be kept in mind when critically evaluating beneficial effects of any kind of treatment for sleep disordered breathing. The presented review intends to initiate an open and critical discussion on the available treatment options. PMID- 22073074 TI - Perioperative risks and their management in patients with sleep-related breathing disorders. AB - Patients with sleep apnea syndromes pose several challenges to the anaesthetist. These are resulting from comorbidity, but mainly from special requirements for pre-, intra- and postoperative management.Frequently, the diagnosis is not known or not diagnosed adequately, making careful preoperative evaluation of the patient by the anaesthetist imperative to identify patients at risk. Besides cardiovascular complications, problems with airway maintenance must be expected, calling for adequate planning. Several general considerations for anaesthesiologic management should be taken into account. The use of short acting pharmacologic agents is recommended to reduce the risk of postoperative episodes of hypoxia following general anaesthesia.Close cooperation of anaesthesia and the surgical specialties involved is the basis for safe management of patients with sleep related syndromes. PMID- 22073076 TI - Central sleep related breathing disorders - diagnostic and therapeutic features. AB - THREE CLASSES OF CENTRAL SRBD ARE DISTINGUISHED: 1. Central sleep apnea (CSA), 2. Cheyne-Stokes Respiration as a subgroup of CSA and 3. central hypoventilation syndromes. Reduced or completely absent central respiratory drive without upper airway obstruction is the common feature of central SRBD. Hypoventilation syndromes most often occur secondary in patients with neuromuscular, pulmonary or sceletal diseases or in patients with massive obesity. In patients with hypoventilation during sleep nocturnal and exertional dyspnea and headaches are frequently reported symptoms. Excessive daytime sleepiness is the key symptom in patients with central sleep apnea syndrome. Cheyne-Stokes Respiration is frequent in heart failure patients but in many cases does not cause symptoms specific for the breathing disorder. If there are symptoms or if ambulatory recording of breathing during sleep suggests a sleep related breathing disorder, polysomnography is then performed to definitively rule out or confirm the diagnosis and to initiate treatment, if needed. The indication for treatment in asymptomatic patients with central sleep apnea and Cheyne-Stokes Respiration may be difficult, as there are very little data concerning the long-term benefit in these patients. Symptomatic patients and those with severe central sleep apnea should be treated. Oxygen and CPAP may be effective in 20-30% of patients each. If these treatment options are ineffective, non-invasive pressure support ventilaiton can be used. In patients suffering from hypoventilation syndromes the treatment of choice is non-invasive pressure support ventilaiton combined with supplemental oxygen, if required. PMID- 22073075 TI - Selective indication for positive airway pressure (PAP) in sleep-related breathing disorders with obstruction. AB - Positive airway pressure (PAP) is the therapy of choice for most sleep-related breathing disorders (SRBD). A variety of PAP devices using positive airway pressure (CPAP, BiPAP, APAP, ASV) must be carefully considered before application. This overview aims to provide criteria for choosing the optimal PAP device according to severity and type of sleep-related breathing disorder. In addition, the range of therapeutic applications, constraints and side effects as well as alternative methods to PAP will be discussed. This review is based on an analysis of current literature and clinical experience. The data is presented from an ENT-sleep-laboratory perspective and is designed to help the ENT practitioner initiate treatment and provide support. Different titration methods, current devices and possible applications will be described. In addition to constant pressure devices (CPAP), most commonly used for symptomatic obstructive sleep apnoea (OSA) without complicating conditions, BiPAP models will be introduced. These allow two different positive pressure settings and are thus especially suitable for patients with cardiopulmonary diseases or patients with pressure intolerance, increasing compliance in this subgroup considerably. Compliance can also be increased in patients during first night of therapy, patients with highly variable pressure demands or position-dependent OSA, by using self-regulating Auto-adjust PAP devices (Automatic positive airway pressure, APAP). Patients with Cheyne-Stokes breathing, a subtype of central sleep apnoea, benefit from adaptive servo-ventilation (ASV), which analyzes breathing patterns continually and adjusts the actual ventilation pressure accordingly. This not only reduces daytime sleepiness, but can also influence heart disease positively. Therapy with positive airway pressure is very effective in eliminating obstruction-related sleep diseases and symptoms. However, because therapy is generally applied for life, the optimal PAP device must be carefully selected, taking into account side effects that influence compliance. PMID- 22073078 TI - Reconstruction of the auricle. AB - Reconstructive and aesthetic surgery of the auricle is one of the most challenging and diverse tasks in plastic head and neck surgery. Injuries, defects and malformations require multiple different techniques, some of which are standardized, other situations require huge experience and artistic creativity. It is a specialty that will never become monotone. PMID- 22073077 TI - Reconstruction of middle ear malformations. AB - Malformations of the middle ear are classified as minor and major malformations. Minor malformations appear with regular external auditory canal, tympanic membrane and aerated middle ear space. The conducting hearing loss is due to fixation or interruption of the ossicular chain. The treatment is surgical, following the rules of ossiculoplasty and stapes surgery. In major malformations (congenital aural atresia) there is no external auditory canal and a deformed or missing pinna. The mastoid and the middle ear space may be underdevelopped, the ossicular chain is dysplastic. Surgical therapy is possible in patients with good aeration of the temporal bone, existing windows, a near normal positioned facial nerve and a mobile ossicular chain. Plastic and reconstructive surgery of the pinna should proceed the reconstruction of the external auditory canal and middle ear. In cases of good prognosis unilateral aural atresia can be approached already in childhood. In patients with high risk of surgical failure, bone anchored hearing aids are the treatment of choice. Recent reports of implantable hearing devices may be discussed as an alternative treatment for selected patients. PMID- 22073079 TI - Complications of auricular correction. AB - The risk of complications of auricular correction is underestimated. There is around a 5% risk of early complications (haematoma, infection, fistulae caused by stitches and granulomae, allergic reactions, pressure ulcers, feelings of pain and asymmetry in side comparison) and a 20% risk of late complications (recurrences, telehone ear, excessive edge formation, auricle fitting too closely, narrowing of the auditory canal, keloids and complete collapse of the ear). Deformities are evaluated less critically by patients than by the surgeons, providing they do not concern how the ear is positioned. The causes of complications and deformities are, in the vast majority of cases, incorrect diagnosis and wrong choice of operating procedure. The choice of operating procedure must be adapted to suit the individual ear morphology. Bandaging technique and inspections and, if necessary, early revision are of great importance for the occurence and progress of early complications, in addition to operation techniques. In cases of late complications such as keloids and auricles that are too closely fitting, unfixed full-thickness skin flaps have proved to be the most successful. Large deformities can often only be corrected to a limited degree of satisfaction. PMID- 22073080 TI - Otoplasty - techniques, characteristics and risks. AB - The protruding ear as a minor ear abnormality is found in approx. 5% of the German population and may give rise to serious emotional problems in children and also in adults. In general, the procedure used for the surgical correction of protruding ears (otoplasty) is a combination of incision, scoring and suture techniques. The choice of the surgical procedure is based on the severity of the ear abnormality and the individual characteristics of the auricular cartilage. In children up to the age of ten years, a soft, elastic or easily pliable auricular cartilage is often still present. In this situation, gentle suture techniques, such as a suturing technique described by Mustarde, are frequently enough to achieve a cosmetically good and lasting result. In adults, the auricular cartilage has already become stiff. Therefore, a combination of incision, scoring and suture techniques is usually required. Apart from reducing the cephaloauricular angle to 15-20 degrees , emphasis on the antihelical fold and a smooth rim of the helix without interruption of the contour are desirable outcomes of this operation. Occasionally, surgical fixation (lobulopexy) may be required to treat protruding lobules or, in rare cases, an additional conchal reduction may become necessary in cases of conchal hyperplasia. Since postoperative complications can often result in severe auricular deformities, as a matter of principle, each ear should be analysed individually regarding its problem areas, and the surgical approach that causes the least injury to the cartilage should be used. PMID- 22073081 TI - Classification and diagnosis of ear malformations. AB - In the ENT region 50% of the malformations affect the ear. Malformations of the outer and middle ear are predominantly unilateral (ca. 70-90%) and mostly involve the right ear. Inner ear malformations can be unilateral or bilateral. The incidence of ear malformations is approximately 1 in 3800 newborns. Ear malformations may be genetic (associated with syndromes or not, with family history, spontaneous mutations) or acquired in nature. Malformations can affect the outer ear (pinna and external auditory canal, EAC), middle ear and inner ear, not infrequently in combination. Formal classification is advisable in order to be able to predict the prognosis and compare treatment schedules. Various classifications have been proposed: pinna and EAC malformations according to Weerda [1], middle ear malformations according to Kosling [2], and inner ear malformations according to Jackler [3], [4], to Marangos [5] and to Sennaroglu [6]. Additionally, we describe Altmann's classification of atresia auris congenita [7] and the Siegert-Mayer-Weerda score [8] for EAC and middle ear malformations, systems of great practicability that are in widespread clinical use. The diagnostic steps include clinical examination, audiological testing, genetic analysis and, especially, CT and MRI. These imaging methods are most usefully employed in combination. Precise description of the malformations by means of CT and MRI is indispensable for the planning and successful outcome of operative ear reconstruction and rehabilitation procedures, including cochlear implantation. PMID- 22073082 TI - Implants for reconstructive surgery of the nose and ears. AB - Implants shorten reconstruction, reduce trauma for the patients, are, in principle, of unlimited availability and can be given definable qualities that outnumber those of biological transplants. Lots of sometimes exotic materials have already been suggested for facial surgery and most of them have turned out to be unsuitable in the short or long term, because they did not satisfactorily fulfil the requirements of a "perfect implant". However, transplants obviously cannot be regarded as ideal either because they often involve the necessity of a second intervention for removal, they are only available to a limited extent and some are at risk of postoperative deflection, shrinkage and absorption. This article is concerned with current knowledge about implant materials for rhinoplasty and ear reconstruction. Autogenous transplants will also be briefly discussed. The repetition of known facts should be largely avoided. In relation to this reference will be made to earlier papers [1]. PMID- 22073083 TI - Disorders of the nasal valve area. AB - The nasal valve area is not a singular structure, but a complex three-dimensional construct consisting of several morphological structures. From the physiologic point of view, it is the place of maximum nasal flow resistance ("flow limiting segment"). Therefore, according to Poiseuille's law, even minor constrictions of this area result in a clinically relevant impairment of nasal breathing for the patient. This narrow passage, also called "ostium internum nasi", is formed by the mobile lateral nasal wall, the anterior septum with the swell body, the head of the inferior turbinate and the osseous piriform aperture. Within the framework of aetiology, static and dynamic disorders of the nasal valve area have to be distinguished since they result in different therapeutic measures. In the context of diagnosis, the exploration of the case history for assessing the patient's extent of suffering and the clinical examination are very important. In addition to the presentation of the basics of disorders of the nasal valves, this paper focuses on the treatment of dynamic disorders that mainly constitute the more important therapeutic issue. In this context, we distinguish between stabilisation techniques through grafts or implants and stabilising suture techniques. Following a thorough analysis, the correction of static nasal valve disorders requires various plastic-reconstructive measures using transposition grafting and skin or composite grafts. PMID- 22073084 TI - Risks and complications in rhinoplasty. AB - Rhinoplasty is regarded to be associated with many risks as the expectations of patient and physician are not always corresponding. Besides of postoperative deformities many other risks and complications have to be considered. Reduction rhinoplasty e.g. can cause breathing disturbances which are reported in 70% of all revision-rhinoplasty-patients. One has to be aware however that scars and loss of mucosal-sensation can also give the feeling of a "blocked nose". The main risks of autogenous transplants are dislocation and resorption, while alloplasts can cause infection and extrusion. In this respect silicone implants can have a complication rate between 5-20%. Less complications are reported with other materials like Gore-Tex. Complications of skin and soft tissues can be atrophy, fibrosis, numbness, cysts originating from displaced mucosa or subcutaneous granulomas caused by ointment material. Postoperative swelling depends mainly on the osteotomy technique. Percutaneous osteotomies cause less trauma, but may result in visible scars. Infections are rare but sometimes life-threatening (toxic-shock-syndrome). The risk is higher, when sinus surgery and rhinoplasty are combined. Osteotomies can also cause injuries of the orbital region. Necrosis of eye-lids by infections and blindness by central artery occlusion are known. There are reports on various other risks like rhinoliquorrhea, brain damage, fistulas between sinus-cavernosus and carotid artery, aneurysms and thrombosis of the cavernous sinus. Discoloration of incisors are possible by damage of vessels and nerves. Rhinoplasty can also become a court-case in dissatisfied patients, a situation that may be called a "typical complication of rhinoplasty". It can be avoided by proper patient selection and consideration of psychological disturbances. Postoperative deformities are considered as main risks of rhinoplasty, causing revision surgery in 5% to 15% of the cases. The analysis of postoperative deformities allowes the identification of specific risks. The most frequent postoperative deformity is the "pollybeak" when a deep naso-frontal angle, cartilaginous hump and reduced tip projection are present preoperatively. The pollybeak is the indication in about 50% of all revision rhinoplasties. Other frequent postoperative deformities are a pendant and wide nasal tip, retractions of the columella base or irregularities of the nasal dorsum. These deformities are very often combined and caused by a loss of septal support. This is why the stability of the caudal septum in septorhinoplasty is the key for a predictable result. Maintaining the position of the tip and the columella is one of the main issues to avoid typical postoperative deformities. The risks for rhinoplasty complications can be reduced with increasing experience. A prerequisite is continuing education and an earnest distinction between complication and mistake. PMID- 22073087 TI - An update on functional and aesthetic surgery of the nose and ear. PMID- 22073086 TI - Surgery of the nasal septum and turbinates. AB - The following article presents nasal septum and turbinate surgery. First an overview with special consideration of the anatomical and physiological background is given followed by indications for surgical procedures. Key steps of the gold standard procedure first described by Cottle and common variations are presented. Furthermore, some techniques dealing with special problems of the septumplasty are discussed followed by an overview on complications and long term results. However, it should be mentioned that studies on surgical procedures of the nasal septum are still not sufficient as higher evidence levels are very rare. Within a separated chapter techniques for closure of septum perforations are presented and indications particularly in the background of the standard procedure of bridge flaps forwarded by Schultz-Coulon are discussed. The second part focusses on turbinate surgery. Accordingly, anatomical and physiological basics are presented followed by indications for surgical procedures and the surgical steps of different procedures as well as postsurgical treatment and long term results. PMID- 22073085 TI - Rhinoplasty - indications and techniques. AB - Rhinoplasty is considered to be one of the most challenging procedures in otolaryngology head and neck surgery. Meticulous planning and excellent surgical skills are pre-requisites for reproducible good outcomes. More than 100 years after the first rhinoplasty, many controversies regarding indication and techniques remain unresolved. The aim of this article is to review current concepts and arguments. PMID- 22073088 TI - Health economic analysis of screening. AB - In this article health economic implications of screening are analysed. First, requirements screening programmes should fulfil are derived, and methodical standards of health economic evaluation are outlined.Using the example of newborn hearing screening, it is then examined if empirical studies meet the methodical requirements of health economic evaluation. Some deficits are realised: Health economic studies of newborn hearing screening are not randomised, most studies are even not controlled. Therefore, most studies do not present incremental, but only average cost-effectiveness ratios (i.e. cost per case identified). Furthermore, evidence on long-term outcomes of screening and early interventions is insufficient. In conclusion, there is a need for controlled trials to examine differences in identified cases, but particularly to examine long-term effects. PMID- 22073089 TI - Genetic analysis for early diagnosis of otorhinolaryngeal diseases. AB - Familiarity with the concepts and methods of human genetics is important in order to be able to perform genetic analysis. The grade of predictability of a genetic disease is partly given by formal genetics but also depends on the importance of the mutated gene for the phenotype.Possibilities for genetic analysis range from differential diagnosis to predictive diagnosis to prenatal diagnosis. After initial consultation in which the physician fully explains the procedure to the patient, it is mandatory that the patient give his full consent.This article summarises and evaluates current knowledge about genetic analysis of important otorhinolaryngeal diseases, including hereditary hearing disabilities, olfactory malfunction, hereditary tumorous diseases, hereditary syndromes and dysplasias. In addition, this article discusses genetic diseases that affect voice and speech, highlights the relevance of human genetic consultation and discusses the importance of embedding genetic analysis in medicine in general. PMID- 22073090 TI - Early diagnosis of sleep related breathing disorders. AB - Obstructive sleep apnea (OSA) being the most frequent sleep related breathing disorder results in non-restorative sleep, an increased cardiovascular morbidity and mortality as well as an elevated number of accidents. In Germany at least two million people have to be expected. If obstructive sleep apnea is diagnosed early enough then sleep may regain its restorative function, daytime performance may be improved and accident risk as well as cardiovascular risk may be normalised. This review critically evaluates anamnestic parameters, questionnaires, clinical findings and unattended recordings during sleep regarding their diagnostic accurracy in recognising OSA. There are numerous tools with insufficient results or too few data disqualifying them for screening for OSA. Promising preliminary results are published concerning neural network analysis of a high number of clinical parameters and non-linear analysis of oximetry itself or in combination with heart rate. Nasal pressure recordings can be used for risk estimation even without expertise in sleep medicine. More data is needed. Unattended portable monitoring used by qualified physicians is the gold standard procedure when screening methods for OSA are compared. It has a very high sensitivity and specificity well documented by several meta-analyses. PMID- 22073091 TI - Early detection of allergic diseases in otorhinolaryngology. AB - Asthmatic diseases have been reported since the ancient world. Hay fever for instance, was described for the first time in the late 18(th) century, and the term "allergy" was introduced about 100 years ago. Today the incidence of allergies is rising; almost one third of the Western population suffers from its side effects. Allergies are some of the most chronic medical complaints, which results in high health expenditures. Therefore, they have a large health and political relevance.Caused by genetic and environmental factors, the group of IgE mediated allergies is large. It consists of e.g. atopic dermatitis, allergic asthma or allergic rhinitis. This paper aims to emphasize the ways of early diagnosis of allergic rhinitis (AR) as AR represents the most important representative of allergic diseases in ENT. PMID- 22073092 TI - Early detection of hearing loss. AB - The universal newborn hearing screening (UNHS) is currently spreading in Germany, as well, even though there can be no talk of a comprehensive establishment. The introduction of UNHS in several federal states such as Hamburg, Hessen, and Schleswig-Holstein can be ascribed to the personal commitment of individual pediatric audiologists. Apart from the procurement of the screening equipment and the training of the staff responsible for the examination of the newborns, the tracking, i.e. the follow-up on children with conspicuous test results, is of utmost importance. This involves significant administration effort and work and is subject to data protection laws that can differ substantially between the various federal states. Among audiologists, there is consensus that within the first three months of a child's life, a hearing loss must be diagnosed and that between the age of 3 and 6 months, the supply of a hearing aid must have been initiated. For this purpose, screening steps 1 (usually a TEOAE measurement) and 2 (AABR testing) need to be conducted in the maternity hospital. The follow-up of step 1 then comprises the repetition of the TEOAE- and AABR measurement for conspicuous children by a specialized physician. The follow-up of step 2 comprises the confirmatory diagnostics in a pediatric audiological center. This always implies BERA diagnostics during spontaneous sleep or under sedation. The subsequent early supply of a hearing aid should generally be conducted by a (pediatric) acoustician specialized on children. PMID- 22073094 TI - Tissue adhesives in otorhinolaryngology. AB - The development of medical tissue adhesives has a long history without finding an all-purpose tissue adhesive for clinical daily routine. This is caused by the specific demands which are made on a tissue adhesive, and the different areas of application. In otorhinolaryngology, on the one hand, this is the mucosal environment as well as the application on bones, cartilage and periphery nerves. On the other hand, there are stressed regions (skin, oral cavity, pharynx, oesophagus, trachea) and unstressed regions (middle ear, nose and paranasal sinuses, cranial bones). But due to the facts that adhesives can have considerable advantages in assuring surgery results, prevention of complications and so reduction of medical costs/treatment expenses, the search for new adhesives for use in otorhinolaryngology will be continued intensively. In parallel, appropriate application systems have to be developed for microscopic and endoscopic use. PMID- 22073093 TI - Early detection in head and neck cancer - current state and future perspectives. AB - Survival and quality of life in head and neck cancer are directly linked to the size of the primary tumor at first detection. In order to achieve substantial gain at these issues, both, primary prevention and secondary prevention, which is early detection of malignant lesions at a small size, have to be improved. So far, there is not only a lack in the necessary infrastructure not only in Germany, but rather worldwide, but additionally the techniques developed so far for early detection have a significance and specificity too low as to warrant safe implementation for screening programs. However, the advancements recently achieved in endoscopy and in quantitative analysis of hypocellular specimens open new perspectives for secondary prevention. Chromoendoscopy and narrow band imaging (NBI) pinpoint suspicious lesions more easily, confocal endomicroscopy and optical coherence tomography obtain optical sections through those lesions, and hyperspectral imaging classifies lesions according to characteristic spectral signatures. These techniques therefore obtain optical biopsies. Once a "bloody" biopsy has been taken, the plethora of parameters that can be quantified objectively has been increased and could be the basis for an objective and quantitative classification of epithelial lesions (multiparametric cytometry, quantitative histology). Finally, cytomics and proteomics approaches, and lab-on the-chip technology might help to identify patients at high-risk. Sensitivity and specificity of these approaches have to be validated, yet, and some techniques have to be adapted for the specific conditions for early detection of head and neck cancer. On this background it has to be stated that it is still a long way to go until a population based screening for head and neck cancer is available. The recent results of screening for cancer of the prostate and breast highlight the difficulties implemented in such a task. PMID- 22073095 TI - Nasal packing and stenting. AB - Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue. PMID- 22073097 TI - Larynx: implants and stents. AB - In the human larynx, implants a primarily used for the correction of glottis insufficiency. In a broader sense laryngeal stents may be considered as implants as well. Laryngeal implants can be differentiated into injectable and solid. The most important representatives of both groups are discussed in detail along with the respective technique of application. Laryngeal stents are primarily used perioperatively. Different types and their use are presented. PMID- 22073096 TI - Implant-retained craniofacial prostheses for facial defects. AB - Craniofacial prostheses, also known as epistheses, are artificial substitutes for facial defects. The breakthrough for rehabilitation of facial defects with implant-retained prostheses came with the development of the modern silicones and bone anchorage. Following the discovery of the osseointegration of titanium in the 1950s, dental implants have been made of titanium in the 1960s. In 1977, the first extraoral titanium implant was inserted in a patient. Later, various solitary extraoral implant systems were developed. Grouped implant systems have also been developed which may be placed more reliably in areas with low bone presentation, as in the nasal and orbital region, or the ideally pneumatised mastoid process. Today, even large facial prostheses may be securely retained. The classical atraumatic surgical technique has remained an unchanged prerequisite for successful implantation of any system. This review outlines the basic principles of osseointegration as well as the main features of extraoral implantology. PMID- 22073098 TI - Tracheostomy cannulas and voice prosthesis. AB - Cannulas and voice prostheses are mechanical aids for patients who had to undergo tracheotomy or laryngectomy for different reasons. For better understanding of the function of those artificial devices, first the indications and particularities of the previous surgical intervention are described in the context of this review. Despite the established procedure of percutaneous dilatation tracheotomy e.g. in intensive care units, the application of epithelised tracheostomas has its own position, especially when airway obstruction is persistent (e.g. caused by traumata, inflammations, or tumors) and a longer artificial ventilation or special care of the patient are required. In order to keep the airways open after tracheotomy, tracheostomy cannulas of different materials with different functions are available. For each patient the most appropriate type of cannula must be found. Voice prostheses are meanwhile the device of choice for rapid and efficient voice rehabilitation after laryngectomy. Individual sizes and materials allow adaptation of the voice prostheses to the individual anatomical situation of the patients. The combined application of voice prostheses with HME (Head and Moisture Exchanger) allows a good vocal as well as pulmonary rehabilitation. Precondition for efficient voice prosthesis is the observation of certain surgical principles during laryngectomy. The duration of the prosthesis mainly depends on material properties and biofilms, mostly consisting of funguses and bacteries. The quality of voice with valve prosthesis is clearly superior to esophagus prosthesis or electro-laryngeal voice. Whenever possible, tracheostoma valves for free-hand speech should be applied. Physicians taking care of patients with speech prostheses after laryngectomy should know exactly what to do in case the device fails or gets lost. PMID- 22073099 TI - Polymeric implant materials for the reconstruction of tracheal and pharyngeal mucosal defects in head and neck surgery. AB - The existing therapeutical options for the tracheal and pharyngeal reconstruction by use of implant materials are described. Inspite of a multitude of options and the availability of very different materials none of these methods applied for tracheal reconstruction were successfully introduced into the clinical routine. Essential problems are insufficiencies of anastomoses, stenoses, lack of mucociliary clearance and vascularisation. The advances in Tissue Engineering (TE) offer new therapeutical options also in the field of the reconstructive surgery of the trachea. In pharyngeal reconstruction far reaching developments cannot be recognized at the moment which would allow to give a prognosis of their success in clinical application. A new polymeric implant material consisting of multiblock copolymers was applied in our own work which was regarded as a promising material for the reconstruction of the upper aerodigestive tract (ADT) due to its physicochemical characteristics. In order to test this material for applications in the ADT under extreme chemical, enzymatical, bacterial and mechanical conditions we applied it for the reconstruction of a complete defect of the gastric wall in an animal model. In none of the animals tested either gastrointestinal complications or negative systemic events occurred, however, there was a multilayered regeneration of the gastric wall implying a regular structured mucosa.In future the advanced stem cell technology will allow further progress in the reconstruction of different kind of tissues also in the field of head and neck surgery following the principles of Tissue Engineering. PMID- 22073100 TI - Biomaterials in skull base surgery. AB - Reconstruction materials and techniques for the base of the skull have undergone rapid developments and differentiation in recent years. While mostly autotransplants, collagens or resorbable alloplastic materials are preferred for duraplasties, pronounced organ-specific differences can be observed in the reconstruction of hard tissues. The use of polymethylmethacryl bone cement, once wide-spread, has decreased greatly due to the release of toxic monomers. Bony autotransplants are still used primarily for smaller skull-base defects, intraoperatively formable titanium nets may be also used for larger fronto- or laterobasal reconstructions of bony defects. Defects in visible areas are increasingly closed with preformed titanium or ceramic implants, which are planned and fitted to the individual patient using preoperative CT imaging. At the skull base, this applies especially to reconstructions of the frontal sinus. For extensive reconstructions of the orbita, titanium nets and non-resorbable plastics have proven valuable; in closing smaller defects especially of the orbital floor, resorbable implants based on Polyglactin 901 are also used. PMID- 22073101 TI - Biomaterials for craniofacial reconstruction. AB - Biomaterials for reconstruction of bony defects of the skull comprise of osteosynthetic materials applied after osteotomies or traumatic fractures and materials to fill bony defects which result from malformation, trauma or tumor resections. Other applications concern functional augmentations for dental implants or aesthetic augmentations in the facial region. For ostheosynthesis, mini- and microplates made from titanium alloys provide major advantages concerning biocompatibility, stability and individual fitting to the implant bed. The necessity of removing asymptomatic plates and screws after fracture healing is still a controversial issue. Risks and costs of secondary surgery for removal face a low rate of complications (due to corrosion products) when the material remains in situ. Resorbable osteosynthesis systems have similar mechanical stability and are especially useful in the growing skull. The huge variety of biomaterials for the reconstruction of bony defects makes it difficult to decide which material is adequate for which indication and for which site. The optimal biomaterial that meets every requirement (e.g. biocompatibility, stability, intraoperative fitting, product safety, low costs etc.) does not exist. The different material types are (autogenic) bone and many alloplastics such as metals (mainly titanium), ceramics, plastics and composites. Future developments aim to improve physical and biological properties, especially regarding surface interactions. To date, tissue engineered bone is far from routine clinical application. PMID- 22073102 TI - Passive and active middle ear implants. AB - Besides eradication of chronic middle ear disease, the reconstruction of the sound conduction apparatus is a major goal of modern ear microsurgery. The material of choice in cases of partial ossicular replacement prosthesis is the autogenous ossicle. In the event of more extensive destruction of the ossicular chain diverse alloplastic materials, e.g. metals, ceramics, plastics or composits are used for total reconstruction. Their specialised role in conducting sound energy within a half-open implant bed sets high demands on the biocompatibility as well as the acoustic-mechanic properties of the prosthesis. Recently, sophisticated titanium middle ear implants allowing individual adaptation to anatomical variations are widely used for this procedure. However, despite modern developments, hearing restoration with passive implants often faces its limitations due to tubal-middle-ear dysfunction. Here, implantable hearing aids, successfully used in cases of sensorineural hearing loss, offer a promising alternative. This article reviews the actual state of affairs of passive and active middle ear implants. PMID- 22073103 TI - Biomaterials in cochlear implants. AB - The cochlear implant (CI) represents, for almost 25 years now, the gold standard in the treatment of children born deaf and for postlingually deafened adults. These devices thus constitute the greatest success story in the field of 'neurobionic' prostheses. Their (now routine) fitting in adults, and especially in young children and even babies, places exacting demands on these implants, particularly with regard to the biocompatibility of a CI's surface components. Furthermore, certain parts of the implant face considerable mechanical challenges, such as the need for the electrode array to be flexible and resistant to breakage, and for the implant casing to be able to withstand external forces.As these implants are in the immediate vicinity of the middle-ear mucosa and of the junction to the perilymph of the cochlea, the risk exists - at least in principle - that bacteria may spread along the electrode array into the cochlea. The wide-ranging requirements made of the CI in terms of biocompatibility and the electrode mechanism mean that there is still further scope - despite the fact that CIs are already technically highly sophisticated - for ongoing improvements to the properties of these implants and their constituent materials, thus enhancing the effectiveness of these devices.This paper will therefore discuss fundamental material aspects of CIs as well as the potential for their future development. PMID- 22073104 TI - Current requirements for polymeric biomaterials in otolaryngology. AB - In recent years otolaryngology was strongly influenced by newly developed implants which are based on both, innovative biomaterials and novel implant technologies. Since the biomaterials are integrated into biological systems they have to fulfill all technical requirements and accommodate biological interactions. Technical functionality relating to implant specific mechanical properties, a sufficiently high stability in terms of physiological conditions, and good biocompatibility are the demands with regard to suitability of biomaterials. The goal in applying biomaterials for implants is to maintain biofunctionality over extended periods of time. These general demands to biomaterials are equally valid for use in otolaryngology. Different classes of materials can be utilized as biomaterials. Metals belong to the oldest biomaterials. In addition, alloys, ceramics, inorganic glasses and composites have been tested successfully. Furthermore, natural and synthetic polymers are widely used materials, which will be in the focus of the current article with regard to their properties and usage as cochlear implants, osteosynthesis implants, stents, and matrices for tissue engineering. Due to their application as permanent or temporary implants materials are differentiated into biostable and biodegradable polymers. The here identified general and up to date requirements for biomaterials and the illustrated applications in otolaryngology emphasize ongoing research efforts in this area and at the same time demonstrate the high significance of interdisciplinary cooperation between natural sciences, engineering, and medical sciences. PMID- 22073105 TI - Structural grafts and suture techniques in functional and aesthetic rhinoplasty. AB - Rhinoplasty has undergone important changes. With the advent of the open structure approach, requirements for structural grafting and direct manipulation of the cartilaginous skeleton through suture techniques have increased substantially. The present review analyzes the current literature on frequently referenced structural grafts and suture techniques. Individual techniques are described and their utility is discussed in light of available studies and data. PMID- 22073106 TI - Nasal surgery in patients with systemic disorders. AB - Multisystemic disorders represent a heterogenous group of diseases which can primarily manifest at the nose and paranasal sinuses as limited disease or secondarily as part of systemic involvement. Rhinologists therefore play an important role in the diagnostic but also therapeutic process. Although therapy of multisystemic disorders is primary systemic, additional rhinosurgery may become necessary. The spectrum of procedures consists of sinus surgery, surgery of the orbit and lacrimal duct, septorhinoplasty and closure of nasal septal perforation. Since the prevalence of most systemic diseases is very rare, recommendations are based on the analysis of single case reports and case series with a limited number of patients only. Although data is still limited, experiences published so far have shown that autologous cartilage or bone grafts can be used in nasal reconstruction of deformities caused by tuberculosis, leprosy, Wegener's granulomatosis, sarcoidosis and relapsing polychondritis. Experiences gained from these diseases support the concept that well-established techniques of septorhinoplasty can be used in systemic diseases as well. However, a state of remission is an essential condition before considering any rhinosurgery in these patients. Even under these circumstances revision surgery has to be expected more frequently compared to the typical collective of patients undergoing septorhinoplasty. In addition, experiences gained from saddle nose reconstruction may in part be of value for the treatment of nasal septal perforations since implantation of cartilage grafts often represents an essential step in multilayer techniques of closure of nasal septal perforations. Aside from the treatment of orbital complications sinus surgery has been proven beneficial in reducing nasal symptoms and increasing quality of life in patients refractory to systemic treatment. PMID- 22073107 TI - Surgery of the turbinates and "empty nose" syndrome. AB - Surgical therapy of the inferior and/or middle turbinate is indicated when conservative treatment options have failed. The desired goal is a reduction of the soft tissue volume of the turbinates regarding the individual anatomic findings, whilst simultaneously conserving as much mucosa as possible. As the turbinates serve as a functional entity within the nose, they ensure climatisation, humidification and cleaning of the inhaled air. Thus free nasal breathing means a decent quality of life, as well.Regarding the multitude of different surgical techniques, we confirm that no ideal standard technique for turbinate reduction has been developed so far. Moreover, there is a lack of prospective and comparable long-term studies, which makes it difficult to recommend evidence-based surgical techniques. However, the anterior turbinoplasty seems to fulfil the preconditions of limited tissue reduction and mucosa preservation, and therefore it is the method of choice today.Radical resection of the turbinates may lead to severe functional disturbances developing a secondary atrophic rhinitis. The "empty nose" syndrome is a specific entity within the secondary atrophic rhinitis where intranasal changes in airflow result in disturbed climatisation and also interfere with pulmonary function. Results deriving from an actual in vivo study of climatisation and airflow in "empty nose" patients are presented. PMID- 22073108 TI - Interaction between otorhinolaryngology and orthodontics: correlation between the nasopharyngeal airway and the craniofacial complex. AB - In terms of pathophysiology, an anatomically narrow airway is a predisposing factor for obstruction of the upper respiratory tract. The correlation between the nasopharyngeal airway and the craniofacial structures is discussed in this context. Thus a mutual interaction between the pharynx and the mandibular position was demonstrated, whereby the transverse dimension of the nasopharynx was significantly larger in patients with prognathism than in patients with retrognathism. The influence of chronic obstruction of the nasal airway on craniofacial development was also discussed. The form-and-function interaction, which ought to explain the causal relationship between nasal obstruction and craniofacial growth, appears to be of a multifactorial rather than a one dimensional, linear nature. It is not disputed, however, that expanding the maxilla improves not only nasal volume and nasal flow, but also the subjective sensation of patients, although it is not possible to make a prognostic statement about the extent of this improvement because of the differing reactions of individuals. Orthodontic appliances for advancing the mandible can also be successfully used in the treatment of mild obstructive sleep apnea syndrome. This treatment method should be considered particularly for patients who are unwilling to undergo or cannot tolerate CPAP (continuous positive airway pressure) treatment. PMID- 22073109 TI - Rhinosurgery in children: developmental and surgical aspects of the growing nose. AB - The anatomy of the nasal skeleton in newborns and adults are not alike. The complete cartilaginous framework of the neonatal nose becomes partly and gradually ossified during the years of growth and is more vulnerable to trauma in that period. Injury in early youth may have large consequences for development and may result in a nasal deformity which will increase during growth and reach its peak during and after the adolescent growth spurt. To understand more of the underlying problems of nasal malformations and their surgical treatment (septorhinoplasty) these items became the focus of multiple animal studies in the last 40 years. The effects of surgery on the nasal septum varied considerably, seemingly depending on which experimental animal was used. In review, however, the very different techniques of the experimental surgery might be even more influential in this respect. Study of one of the larger series of experiments in young rabbits comprised skeletal measurements with statistical analysis, and microscopic observations of the tissues. The behaviour of hyaline cartilage of the human nose appeared to be comparable to that of other mammals. Cartilage, although resilient, can be easily fractured whereas its tendency to integrated healing is very low, even when the perichondrium has been saved. Also surgical procedures - like in septoplasty - may result in growth disturbances of the nasal skeleton like recurrent deviations or duplicature. Loss of cartilage, as might occur after a septum abscess, is never completely restored despite some cartilage regeneration. In this article experimental studies are reviewed and compared.Still there remains a lack of consensus in the literature concerning the developmental effects of rhinosurgry in children.Based on their observations in animals and a few clinical studies, mostly with small numbers of patients but with a long follow-up, the authors have compiled a list of guidelines to be considered before starting to perform surgery on the growing midface in children. PMID- 22073110 TI - Quality of life before and after septoplasty and rhinoplasty. AB - Subjective assessment of quality of life (QOL) as an important aspect of outcomes research has received increasing importance during the past decades. QOL is measured with standardized questionnaires which had been tested with regard to reliability, validity, and sensitivity. Surgical procedures of the nasal septum (septoplasty) and the external nose (rhinoplasty) are frequently performed. Since many years subjectively assessed results of these operations have been reported in the literature. However, validated QOL instruments were applied only for one decade. Beforehand, measurements were performed using retrospective assessment of satisfaction or visual analogue scales. Prospective application of validated disease-specific and general measuring instruments has to be demanded for future studies.Most of the septoplasty patients as well as most of the rhinoplasty patients evaluate the operation being successful. However, a relevant number of patients is not satisfied with the result of surgery. In this context, QOL instruments have the potential to identify further factors influencing the outcome. Especially in rhinoplasty patients, special attention has to be drawn on potential psychosocial effects of the operation. PMID- 22073112 TI - Numerical simulation and nasal air-conditioning. AB - Heating and humidification of the respiratory air are the main functions of the nasal airways in addition to cleansing and olfaction. Optimal nasal air conditioning is mandatory for an ideal pulmonary gas exchange in order to avoid desiccation and adhesion of the alveolar capillary bed. The complex three dimensional anatomical structure of the nose makes it impossible to perform detailed in vivo studies on intranasal heating and humidification within the entire nasal airways applying various technical set-ups. The main problem of in vivo temperature and humidity measurements is a poor spatial and time resolution. Therefore, in vivo measurements are feasible only to a restricted extent, solely providing single temperature values as the complete nose is not entirely accessible. Therefore, data on the overall performance of the nose are only based on one single measurement within each nasal segment. In vivo measurements within the entire nose are not feasible. These serious technical issues concerning in vivo measurements led to a large number of numerical simulation projects in the last few years providing novel information about the complex functions of the nasal airways. In general, numerical simulations merely calculate predictions in a computational model, e.g. a realistic nose model, depending on the setting of the boundary conditions. Therefore, numerical simulations achieve only approximations of a possible real situation. The aim of this review is the synopsis of the technical expertise on the field of in vivo nasal air conditioning, the novel information of numerical simulations and the current state of knowledge on the influence of nasal and sinus surgery on nasal air conditioning. PMID- 22073117 TI - Temporal artery flow response during the last minute of a head up tilt test, in relation with orthostatic intolerance after a 60 day head-down bedrest. AB - OBJECTIVE: Check if the Temporal flow response to Tilt could provide early hemodynamic pattern in the minutes preceding a syncope during the Tilt test performed after a 60-d head down bedrest (HDBR). METHOD: Twenty-one men divided into 3 groups [Control (Con), Resistive Vibration (RVE) and Chinese Herb (Herb)] underwent a 60 day HDBR. Pre and Post HDBR a 20 min Tilt identified Finishers (F) and Non Finishers (NF). Cerebral (MCA), Temporal (TEMP), Femoral (FEM) flow velocity, were measured by Doppler during the Tilt. Blood pressure (BP) was measured by arm cuff and cardiopress. RESULTS AND DISCUSSION: Four of the 21 subjects were NF at the post HDBR Tilt test (Con gr:2, RVE gr: 1, Herb gr: 1). At 1 min and 10 s before end of Tilt in NF gr, FEM flow decreased less and MCA decreased more at post HDBR Tilt compared to pre (p<0.05), while in the F gr they changed similarly as pre. In NF gr: TEMP flow decreased more at post HDBR Tilt compared to pre, but only at 10 s before the end of Tilt (P<0.05). During the last 10 s a negative TEMP diastolic component appeared which induced a drop in mean velocity until Tilt arrest. CONCLUSION: The sudden drop in TEMP flow with onset of a negative diastolic flow preceding the decrease in MCA flow confirm that the TEMP vascular resistance respond more directly than the cerebral one to the cardiac output redistribution and that this response occur several seconds before syncope. PMID- 22073118 TI - A malaria vaccine based on the polymorphic block 2 region of MSP-1 that elicits a broad serotype-spanning immune response. AB - Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed, combined with the relatively conserved Block 1 sequence of MSP-1 and expressed in E.coli. The MSP-1 Hybrid antigen has been produced with high yield by fed-batch fermentation and purified without the aid of affinity tags resulting in a pure and extremely thermostable antigen preparation. MSP-1 hybrid is immunogenic in experimental animals using adjuvants suitable for human use, eliciting antibodies against epitopes from all three Block 2 serotypes. Human serum antibodies from Africans naturally exposed to malaria reacted to the MSP-1 hybrid as strongly as, or better than the same serum reactivities to individual MSP-1 Block 2 antigens, and these antibody responses showed clear associations with reduced incidence of malaria episodes. The MSP-1 hybrid is designed to induce a protective antibody response to the highly polymorphic Block 2 region of MSP-1, enhancing the repertoire of MSP-1 Block 2 antibody responses found among immune and semi-immune individuals in malaria endemic areas. The target population for such a vaccine is young children and vulnerable adults, to accelerate the acquisition of a full range of malaria protective antibodies against this polymorphic parasite antigen. PMID- 22073111 TI - Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses. AB - In this review, anatomy and physiology of the respiratory mucosa of nose and paranasal sinuses are summarized under the aspect of its clinical significance. Basics of endonasal cleaning including mucociliary clearance and nasal reflexes, as well as defence mechanisms are explained. Physiological wound healing, aspects of endonasal topical medical therapy and typical diagnostic procedures to evaluate the respiratory functions are presented. Finally, the pathophysiologies of different subtypes of non-allergic rhinitis are outlined together with treatment recommendations. PMID- 22073119 TI - The practical challenges of evaluating a blanket emergency feeding programme in northern Kenya. AB - A blanket supplementary feeding programme for young children was implemented for four months in five northern districts of Kenya from January 2010 because of fears of food insecurity exacerbated by drought. An attempt to evaluate the impact of the food on children's anthropometric status was put in place in three districts. The main aim of the analysis was to assess the quality of the data on the cohort of children studied in the evaluation and to propose methods by which it could be improved to evaluate future blanket feeding programmes. Data on the name, age, sex, weight and height of a systematic sample of children recruited at 61 food distribution sites were collected at the first, second and third rounds and again at an extra, fifth food distribution, offered only to the evaluation subjects. Of the 3,544 children enrolled, 483 (13.63%) did not collect a fifth ration. Of the 2,640 children who were considered by their name to be the same at the first and fifth food distribution (13% were different), data on only 902 children (34.17%) were considered acceptable based on their age (an arbitrary +/ 3 months different) and their length or height (between >-1 or <=4 cm different) at the two instances they were seen. Data on nearly two thirds of children were of questionable quality. The main reasons for the poor quality data were inconsistencies in estimating age or because caretakers may have brought different children. Recommendations are made about how to improve data quality including ensuring that entry to a blanket feeding programme is clearly based on height, not age, to avoid misreporting age; careful identification of subjects at all contacts; and using well-trained, specialist evaluation staff. PMID- 22073120 TI - In vivo systematic analysis of Candida albicans Zn2-Cys6 transcription factors mutants for mice organ colonization. AB - The incidence of fungal infections in immuno-compromised patients increased considerably over the last 30 years. New treatments are therefore needed against pathogenic fungi. With Candida albicans as a model, study of host-fungal pathogen interactions might reveal new sources of therapies. Transcription factors (TF) are of interest since they integrate signals from the host environment and participate in an adapted microbial response. TFs of the Zn2-Cys6 class are specific to fungi and are important regulators of fungal metabolism. This work analyzed the importance of the C. albicans Zn2-Cys6 TF for mice kidney colonization. For this purpose, 77 Zn2-Cys6 TF mutants were screened in a systemic mice model of infection by pools of 10 mutants. We developed a simple barcoding strategy to specifically detect each mutant DNA from mice kidney by quantitative PCR. Among the 77 TF mutant strains tested, eight showed a decreased colonization including mutants for orf19.3405, orf19.255, orf19.5133, RGT1, UGA3, orf19.6182, SEF1 and orf19.2646, and four an increased colonization including mutants for orf19.4166, ZFU2, orf19.1685 and UPC2 as compared to the isogenic wild type strain. Our approach was validated by comparable results obtained with the same animal model using a single mutant and the revertant for an ORF (orf19.2646) with still unknown functions. In an attempt to identify putative involvement of such TFs in already known C. albicans virulence mechanisms, we determined their in vitro susceptibility to pH, heat and oxidative stresses, as well as ability to produce hyphae and invade agar. A poor correlation was found between in vitro and in vivo assays, thus suggesting that TFs needed for mice kidney colonization may involve still unknown mechanisms. This large-scale analysis of mice organ colonization by C. albicans can now be extended to other mutant libraries since our in vivo screening strategy can be adapted to any preexisting mutants. PMID- 22073121 TI - A multi-sample based method for identifying common CNVs in normal human genomic structure using high-resolution aCGH data. AB - BACKGROUND: It is difficult to identify copy number variations (CNV) in normal human genomic data due to noise and non-linear relationships between different genomic regions and signal intensity. A high-resolution array comparative genomic hybridization (aCGH) containing 42 million probes, which is very large compared to previous arrays, was recently published. Most existing CNV detection algorithms do not work well because of noise associated with the large amount of input data and because most of the current methods were not designed to analyze normal human samples. Normal human genome analysis often requires a joint approach across multiple samples. However, the majority of existing methods can only identify CNVs from a single sample. METHODOLOGY AND PRINCIPAL FINDINGS: We developed a multi-sample-based genomic variations detector (MGVD) that uses segmentation to identify common breakpoints across multiple samples and a k-means based clustering strategy. Unlike previous methods, MGVD simultaneously considers multiple samples with different genomic intensities and identifies CNVs and CNV zones (CNVZs); CNVZ is a more precise measure of the location of a genomic variant than the CNV region (CNVR). CONCLUSIONS AND SIGNIFICANCE: We designed a specialized algorithm to detect common CNVs from extremely high-resolution multi sample aCGH data. MGVD showed high sensitivity and a low false discovery rate for a simulated data set, and outperformed most current methods when real, high resolution HapMap datasets were analyzed. MGVD also had the fastest runtime compared to the other algorithms evaluated when actual, high-resolution aCGH data were analyzed. The CNVZs identified by MGVD can be used in association studies for revealing relationships between phenotypes and genomic aberrations. Our algorithm was developed with standard C++ and is available in Linux and MS Windows format in the STL library. It is freely available at: http://embio.yonsei.ac.kr/~Park/mgvd.php. PMID- 22073122 TI - A point mutation in translation initiation factor eIF2B leads to function--and time-specific changes in brain gene expression. AB - BACKGROUND: Mutations in eukaryotic translation initiation factor 2B (eIF2B) cause Childhood Ataxia with CNS Hypomyelination (CACH), also known as Vanishing White Matter disease (VWM), which is associated with a clinical pathology of brain myelin loss upon physiological stress. eIF2B is the guanine nucleotide exchange factor (GEF) of eIF2, which delivers the initiator tRNA(Met) to the ribosome. We recently reported that a R132H mutation in the catalytic subunit of this GEF, causing a 20% reduction in its activity, leads under normal conditions to delayed brain development in a mouse model for CACH/VWM. To further explore the effect of the mutation on global gene expression in the brain, we conducted a wide-scale transcriptome analysis of the first three critical postnatal weeks. METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide mRNA expression of wild-type and mutant mice was profiled at postnatal (P) days 1, 18 and 21 to reflect the early proliferative stage prior to white matter establishment (P1) and the peak of oligodendrocye differentiation and myelin synthesis (P18 and P21). At each developmental stage, between 441 and 818 genes were differentially expressed in the mutant brain with minimal overlap, generating unique time point-specific gene expression signatures. CONCLUSIONS: The current study demonstrates that a point mutation in eIF2B, a key translation initiation factor, has a massive effect on global gene expression in the brain. The overall changes in expression patterns reflect multiple layers of indirect effects that accumulate as the brain develops and matures. The differentially expressed genes seem to reflect delayed waves of gene expression as well as an adaptation process to cope with hypersensitivity to cellular stress. PMID- 22073123 TI - Structural annotation of Mycobacterium tuberculosis proteome. AB - Of the ~4000 ORFs identified through the genome sequence of Mycobacterium tuberculosis (TB) H37Rv, experimentally determined structures are available for 312. Since knowledge of protein structures is essential to obtain a high resolution understanding of the underlying biology, we seek to obtain a structural annotation for the genome, using computational methods. Structural models were obtained and validated for ~2877 ORFs, covering ~70% of the genome. Functional annotation of each protein was based on fold-based functional assignments and a novel binding site based ligand association. New algorithms for binding site detection and genome scale binding site comparison at the structural level, recently reported from the laboratory, were utilized. Besides these, the annotation covers detection of various sequence and sub-structural motifs and quaternary structure predictions based on the corresponding templates. The study provides an opportunity to obtain a global perspective of the fold distribution in the genome. The annotation indicates that cellular metabolism can be achieved with only 219 folds. New insights about the folds that predominate in the genome, as well as the fold-combinations that make up multi-domain proteins are also obtained. 1728 binding pockets have been associated with ligands through binding site identification and sub-structure similarity analyses. The resource (http://proline.physics.iisc.ernet.in/Tbstructuralannotation), being one of the first to be based on structure-derived functional annotations at a genome scale, is expected to be useful for better understanding of TB and for application in drug discovery. The reported annotation pipeline is fairly generic and can be applied to other genomes as well. PMID- 22073124 TI - Differential modulation of Beta-adrenergic receptor signaling by trace amine associated receptor 1 agonists. AB - Trace amine-associated receptors (TAAR) are rhodopsin-like G-protein-coupled receptors (GPCR). TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR), phenylethylamine (PEA), octopamine (OA), but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous beta-adrenergic receptors 1 (ADRB1) and 2 (ADRB2) have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2 antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR) octopamine (OAR), ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular beta-adrenergic receptor subtypes. PMID- 22073125 TI - A comprehensive evaluation of colonic mucosal isolates of Sutterella wadsworthensis from inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) arises in genetically susceptible individuals as a result of an unidentified environmental trigger, possibly a hitherto unknown bacterial pathogen. Twenty-six clinical isolates of Sutterella wadsworthensis were obtained from 134 adults and 61 pediatric patients undergoing colonoscopy, of whom 69 and 29 respectively had IBD. S. wadsworthensis was initially more frequently isolated from IBD subjects, hence this comprehensive study was undertaken to elucidate its role in IBD. Utilizing these samples, a newly designed PCR was developed, to study the prevalence of this bacterium in adult patients with ulcerative colitis (UC). Sutterella wadsworthensis was detected in 83.8% of adult patients with UC as opposed to 86.1% of control subjects (p = 0.64). Selected strains from IBD cases and controls were studied to elicit morphological, proteomic, genotypic and pathogenic differences. This study reports Scanning Electron Microscopy (SEM) appearances and characteristic MALDI TOF MS protein profiles of S. wadsworthensis for the very first time. SEM showed that the bacterium is pleomorphic, existing in predominantly two morphological forms, long rods and coccobacilli. No differences were noted in the MALDI-TOF mass spectrometry proteomic analysis. There was no distinct clustering of strains identified from cases and controls on sequence analysis. Cytokine response after monocyte challenge with strains from patients with IBD and controls did not yield any significant differences. Our studies indicate that S. wadsworthensis is unlikely to play a role in the pathogenesis of IBD. Strains from cases of IBD could not be distinguished from those identified from controls. PMID- 22073126 TI - Disturbances in body ownership in schizophrenia: evidence from the rubber hand illusion and case study of a spontaneous out-of-body experience. AB - BACKGROUND: A weakened sense of self may contribute to psychotic experiences. Body ownership, one component of self-awareness, can be studied with the rubber hand illusion (RHI). Watching a rubber hand being stroked while one's unseen hand is stroked synchronously can lead to a sense of ownership over the rubber hand, a shift in perceived position of the real hand, and a limb-specific drop in stimulated hand temperature. We aimed to assess the RHI in schizophrenia using quantifiable measures: proprioceptive drift and stimulation-dependent changes in hand temperature. METHODS: The RHI was elicited in 24 schizophrenia patients and 21 matched controls by placing their unseen hand adjacent to a visible rubber hand and brushing real and rubber hands synchronously or asynchronously. Perceived finger location was measured before and after stimulation. Hand temperature was taken before and during stimulation. Subjective strength of the illusion was assessed by a questionnaire. RESULTS: Across groups, the RHI was stronger during synchronous stimulation, indicated by self-report and proprioceptive drift. Patients reported a stronger RHI than controls. Self reported strength of RHI was associated with schizotypy in controls Proprioceptive drift was larger in patients, but only following synchronous stimulation. Further, we observed stimulation-dependent changes in skin temperature. During right hand stimulation, temperature dropped in the stimulated hand and rose in the unstimulated hand. Interestingly, induction of RHI led to an out-of-body experience in one patient, linking body disownership and psychotic experiences. CONCLUSIONS: The RHI is quantitatively and qualitatively stronger in schizophrenia. These findings suggest that patients have a more flexible body representation and weakened sense of self, and potentially indicate abnormalities in temporo-parietal networks implicated in body ownership. Further, results suggest that these body ownership disturbances might be at the heart of a subset of the pathognomonic delusions of passivity. PMID- 22073127 TI - Maternal immunization with pneumococcal surface protein A protects against pneumococcal infections among derived offspring. AB - Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood. PMID- 22073128 TI - Poly(ADP-ribose) polymerase 1 is indispensable for transforming growth factor beta Induced Smad3 activation in vascular smooth muscle cell. AB - BACKGROUND: Transforming growth factor type-beta (TGF-beta)/Smad pathway plays an essential role in vascular fibrosis. Reactive oxygen species (ROS) generation also mediates TGF-beta signaling-induced vascular fibrosis, suggesting that some sort of interaction exists between Smad and redox pathways. However, the underlying molecular mechanism is largely unknown. This study aims to investigate the influence of poly(ADP-ribose) polymerase 1 (PARP1), a downstream effector of ROS, on TGF-beta signaling transduction through Smad3 pathway in rat vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: TGF-beta1 treatment promoted PARP1 activation through induction of ROS generation in rat VSMCs. TGF-beta1 induced phosphorylation and nuclear accumulation of Smad3 was prevented by treatment of cells with PARP inhibitor, 3-aminobenzamide (3AB) or N-(6-oxo-5,6 dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetami (PJ34), or PARP1 siRNA. TGF-beta1 treatment promoted poly(ADP-ribosy)lation of Smad3 via activation of PARP1 in the nucleus. Poly(ADP-ribosy)lation enhanced Smad-Smad binding element (SBE) complex formation in nuclear extracts and increased DNA binding activity of Smad3. Pretreatment with 3AB, PJ34, or PARP1 siRNA prevented TGF-beta1-induced Smad3 transactivation and expression of Smad3 target genes, including collagen Ialpha1, collagen IIIalpha1 and tissue inhibitor of metalloproteinase 1, in rat VSMCs. CONCLUSIONS: PARP1 is indispensable for TGF-beta1 induced Smad3 activation in rat VSMCs. Targeting PARP1 may be a promising therapeutic approach against vascular diseases induced by dysregulation of TGF-beta/Smad3 pathway. PMID- 22073129 TI - An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis. AB - Studies on familial aggregation of cancer may suggest an overall contribution of inherited genes or a shared environment in the development of malignant disease. We performed a meta-analysis on familial clustering of prostate cancer. Out of 74 studies reporting data on familial aggregation of prostate cancer in unselected populations retrieved by a Pubmed search and browsing references, 33 independent studies meeting the inclusion criteria were used in the analysis performed with the random effects model. The pooled rate ratio (RR) for first-degree family history, i.e. affected father or brother, is 2.48 (95% confidence interval: 2.25 2.74). The incidence rate for men who have a brother who got prostate cancer increases 3.14 times (CI:2.37-4.15), and for those with affected father 2.35 times (CI:2.02-2.72). The pooled estimate of RR for two or more affected first degree family members relative to no history in father and in brother is 4.39 (CI:2.61-7.39). First-degree family history appears to increase the incidence rate of prostate cancer more in men under 65 (RR:2.87, CI:2.21-3.74), than in men aged 65 and older (RR:1.92, CI:1.49-2.47), p for interaction = 0.002. The attributable fraction among those having an affected first-degree relative equals to 59.7% (CI:55.6-63.5%) for men at all ages, 65.2% (CI:57.7-71.4%) for men younger than 65 and 47.9% (CI:37.1-56.8%) for men aged 65 or older. For those with a family history in 2 or more first-degree family members 77.2% (CI:65.4 85.0%) of prostate cancer incidence can be attributed to the familial clustering. Our combined estimates show strong familial clustering and a significant effect modification by age meaning that familial aggregation was associated with earlier disease onset (before age 65). PMID- 22073130 TI - A transgenic mouse line expressing cre recombinase in undifferentiated postmitotic mouse retinal bipolar cell precursors. AB - Approaches for manipulating cell type-specific gene expression during development depend on the identification of novel genetic tools. Here, we report the generation of a transgenic mouse line that utilizes Vsx2 upstream sequences to direct Cre recombinase to developing retinal bipolar cells. In contrast to the endogenous Vsx2 expression pattern, transgene expression was not detected in proliferating retinal progenitor cells and was restricted to post-mitotic bipolar cells. Cre immunolabeling was detected in rod bipolar cells and a subset of ON and OFF cone bipolar cells. Expression was first observed at postnatal day 3 and was detectable between 24 hours and 36 hours after the last S-phase of the cell cycle. The appearance of Cre-immunolabeled cells preceded the expression of bipolar cell type-specific markers such as PKCalpha and Cabp5 suggesting that transgene expression is initiated prior to terminal differentiation. In the presence of a constitutive conditional reporter transgene, reporter fluorescence was detected in Cre-expressing bipolar cells in the mature retina as expected, but was also observed in Cre-negative Type 2 bipolar cells and occasionally in Cre-negative photoreceptor cells. Together these findings reveal a new transgenic tool for directing gene expression to post-mitotic retinal precursors that are mostly committed to a bipolar cell fate. PMID- 22073131 TI - Antibodies against alpha-synuclein reduce oligomerization in living cells. AB - Recent research implicates soluble aggregated forms of alpha-synuclein as neurotoxic species with a central role in the pathogenesis of Parkinson's disease and related disorders. The pathway by which alpha-synuclein aggregates is believed to follow a step-wise pattern, in which dimers and smaller oligomers are initially formed. Here, we used H4 neuroglioma cells expressing alpha-synuclein fused to hemi:GFP constructs to study the effects of alpha-synuclein monoclonal antibodies on the early stages of aggregation, as quantified by Bimolecular Fluorescence Complementation assay. Widefield and confocal microscopy revealed that cells treated for 48 h with monoclonal antibodies internalized antibodies to various degrees. C-terminal and oligomer-selective alpha-synuclein antibodies reduced the extent of alpha-synuclein dimerization/oligomerization, as indicated by decreased GFP fluorescence signal. Furthermore, ELISA measurements on lysates and conditioned media from antibody treated cells displayed lower alpha-synuclein levels compared to untreated cells, suggesting increased protein turnover. Taken together, our results propose that extracellular administration of monoclonal antibodies can modify or inhibit early steps in the aggregation process of alpha synuclein, thus providing further support for passive immunization against diseases with alpha-synuclein pathology. PMID- 22073134 TI - Camphene, a plant-derived monoterpene, reduces plasma cholesterol and triglycerides in hyperlipidemic rats independently of HMG-CoA reductase activity. AB - BACKGROUND: Central to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO). METHODOLOGY/PRINCIPAL FINDINGS: The hypolipidemic effect of MGO was investigated in naive as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naive rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 ug/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001), 54% of Low Density Lipoprotein (LDL)-cholesterol (p<0.001) and 34.5% of triglycerides (p<0.001). Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. CONCLUSIONS: Given the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent and merits further evaluation. PMID- 22073135 TI - Rumor has it...: relay communication of stress cues in plants. AB - Recent evidence demonstrates that plants are able not only to perceive and adaptively respond to external information but also to anticipate forthcoming hazards and stresses. Here, we tested the hypothesis that unstressed plants are able to respond to stress cues emitted from their abiotically-stressed neighbors and in turn induce stress responses in additional unstressed plants located further away from the stressed plants. Pisum sativum plants were subjected to drought while neighboring rows of five unstressed plants on both sides, with which they could exchange different cue combinations. On one side, the stressed plant and its unstressed neighbors did not share their rooting volumes (UNSHARED) and thus were limited to shoot communication. On its other side, the stressed plant shared one of its rooting volumes with its nearest unstressed neighbor and all plants shared their rooting volumes with their immediate neighbors (SHARED), allowing both root and shoot communication. Fifteen minutes following drought induction, significant stomatal closure was observed in both the stressed plants and their nearest unstressed SHARED neighbors, and within one hour, all SHARED neighbors closed their stomata. Stomatal closure was not observed in the UNSHARED neighbors. The results demonstrate that unstressed plants are able to perceive and respond to stress cues emitted by the roots of their drought-stressed neighbors and, via 'relay cuing', elicit stress responses in further unstressed plants. Further work is underway to study the underlying mechanisms of this new mode of plant communication and its possible adaptive implications for the anticipation of forthcoming abiotic stresses by plants. PMID- 22073136 TI - Time to recurrence and survival in serous ovarian tumors predicted from integrated genomic profiles. AB - BACKGROUND: Serous ovarian cancer (SeOvCa) is an aggressive disease with differential and often inadequate therapeutic outcome after standard treatment. The Cancer Genome Atlas (TCGA) has provided rich molecular and genetic profiles from hundreds of primary surgical samples. These profiles confirm mutations of TP53 in ~100% of patients and an extraordinarily complex profile of DNA copy number changes with considerable patient-to-patient diversity. This raises the joint challenge of exploiting all new available datasets and reducing their confounding complexity for the purpose of predicting clinical outcomes and identifying disease relevant pathway alterations. We therefore set out to use multi-data type genomic profiles (mRNA, DNA methylation, DNA copy-number alteration and microRNA) available from TCGA to identify prognostic signatures for the prediction of progression-free survival (PFS) and overall survival (OS). METHODOLOGY/PRINCIPAL FINDINGS: We implemented a multivariate Cox Lasso model and median time-to-event prediction algorithm and applied it to two datasets integrated from the four genomic data types. We (1) selected features through cross-validation; (2) generated a prognostic index for patient risk stratification; and (3) directly predicted continuous clinical outcome measures, that is, the time to recurrence and survival time. We used Kaplan-Meier p-values, hazard ratios (HR), and concordance probability estimates (CPE) to assess prediction performance, comparing separate and integrated datasets. Data integration resulted in the best PFS signature (withheld data: p-value = 0.008; HR = 2.83; CPE = 0.72). CONCLUSIONS/SIGNIFICANCE: We provide a prediction tool that inputs genomic profiles of primary surgical samples and generates patient specific predictions for the time to recurrence and survival, along with outcome risk predictions. Using integrated genomic profiles resulted in information gain for prediction of outcomes. Pathway analysis provided potential insights into functional changes affecting disease progression. The prognostic signatures, if prospectively validated, may be useful for interpreting therapeutic outcomes for clinical trials that aim to improve the therapy for SeOvCa patients. PMID- 22073137 TI - Coverage, adherence and costs of intermittent preventive treatment of malaria in children employing different delivery strategies in Jasikan, Ghana. AB - BACKGROUND: Intermittent preventive treatment of malaria in children (IPTc) involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected. IPTc provides a high level of protection against uncomplicated and severe malaria, with monthly sulphadoxine-pyrimethamine plus amodiaquine (SP&AQ) and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens. A key challenge is the identification of a cost effective delivery strategy. METHODS: A community randomized trial was undertaken in Jasikan district, Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways. Twelve villages were randomly selected to receive IPTc from village health workers (VHWs) or facility-based nurses working at health centres' outpatient departments (OPD) or EPI outreach clinics. Children aged 3 to 59 months-old received one IPT course (three doses) in May, June, September and October. Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective. RESULTS: The economic cost per child receiving at least the first dose of all 4 courses was US$4.58 when IPTc was delivered by VHWs, US$4.93 by OPD nurses and US$ 5.65 by EPI nurses. The unit economic cost of receiving all 3 doses of all 4 courses was US$7.56 and US$8.51 when IPTc was delivered by VHWs or facility-based nurses respectively. The main cost driver for the VHW delivery was supervision, reflecting resources used for travelling to more remote communities rather than more intense supervision, and for OPD and EPI delivery, it was the opportunity cost of the time spent by nurses in dispensing IPTc. CONCLUSIONS: VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district, Ghana. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119132. PMID- 22073138 TI - Protein domain of unknown function 3233 is a translocation domain of autotransporter secretory mechanism in gamma proteobacteria. AB - Vibrio cholerae, the enteropathogenic gram negative bacteria is one of the main causative agents of waterborne diseases like cholera. About 1/3(rd) of the organism's genome is uncharacterised with many protein coding genes lacking structure and functional information. These proteins form significant fraction of the genome and are crucial in understanding the organism's complete functional makeup. In this study we report the general structure and function of a family of hypothetical proteins, Domain of Unknown Function 3233 (DUF3233), which are conserved across gram negative gammaproteobacteria (especially in Vibrio sp. and similar bacteria). Profile and HMM based sequence search methods were used to screen homologues of DUF3233. The I-TASSER fold recognition method was used to build a three dimensional structural model of the domain. The structure resembles the transmembrane beta-barrel with an axial N-terminal helix and twelve antiparallel beta-strands. Using a combination of amphipathy and discrimination analysis we analysed the potential transmembrane beta-barrel forming properties of DUF3233. Sequence, structure and phylogenetic analysis of DUF3233 indicates that this gram negative bacterial hypothetical protein resembles the beta-barrel translocation unit of autotransporter Va secretory mechanism with a gene organisation that differs from the conventional Va system. PMID- 22073139 TI - The role of muscarinic receptors in the beneficial effects of adenosine against myocardial reperfusion injury in rats. AB - Adenosine, a catabolite of ATP, displays a wide variety of effects in the heart including regulation of cardiac response to myocardial ischemia and reperfusion injury. Nonetheless, the precise mechanism of adenosine-induced cardioprotection is still elusive. Isolated Sprague-Dawley rat hearts underwent 30 min global ischemia and 120 min reperfusion using a Langendorff apparatus. Both adenosine and acetylcholine treatment recovered the post-reperfusion cardiac function associated with adenosine and muscarinic receptors activation. Simultaneous administration of adenosine and acetylcholine failed to exert any additive protective effect, suggesting a shared mechanism between the two. Our data further revealed a cross-talk between the adenosine and acetylcholine receptor signaling in reperfused rat hearts. Interestingly, the selective M(2) muscarinic acetylcholine receptor antagonist methoctramine significantly attenuated the cardioprotective effect of adenosine. In addition, treatment with adenosine upregulated the expression and the maximal binding capacity of muscarinic acetylcholine receptor, which were inhibited by the selective A(1) adenosine receptor antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) and the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). These data suggested a possible functional coupling between the adenosine and muscarinic receptors behind the observed cardioprotection. Furthermore, nitric oxide was found involved in triggering the response to each of the two receptor agonist. In summary, there may be a cross-talk between the adenosine and muscarinic receptors in ischemic/reperfused myocardium with nitric oxide synthase might serve as the distal converging point. In addition, adenosine contributes to the invigorating effect of adenosine on muscarinic receptor thereby prompting to regulation of cardiac function. These findings argue for a potentially novel mechanism behind the adenosine-mediated cardioprotection. PMID- 22073140 TI - Neonatal overfeeding induced by small litter rearing causes altered glucocorticoid metabolism in rats. AB - Elevated glucocorticoid (GC) activity may be involved in the development of the metabolic syndrome. Tissue GC exposure is determined by the tissue-specific GC activating enzyme 11beta-hydroxysteriod dehydrogenase type 1 (11beta-HSD1) and the GC-inactivating enzyme 5alpha-reductase type 1 (5alphaR1), as well as 5beta reductase (5betaR). Our aim was to study the effects of neonatal overfeeding induced by small litter rearing on the expression of GC-regulating enzymes in adipose tissue and/or liver and on obesity-related metabolic disturbances during development. Male Sprague-Dawley rat pup litters were adjusted to litter sizes of three (small litters, SL) or ten (normal litters, NL) on postnatal day 3 and then given standard chow from postnatal week 3 onward (W3). Small litter rearing induced obesity, hyperinsulinemia, and higher circulating corticosterone in adults. 11beta-HSD1 expression and enzyme activity in retroperitoneal, but not in epididymal, adipose tissue increased with postnatal time and peaked at W5/W6 in both groups before declining. From W8, 11beta-HSD1 expression and enzyme activity levels in retroperitoneal fat persisted at significantly higher levels in SL compared to NL rats. Hepatic 11beta-HSD1 enzyme activity in SL rats was elevated from W3 to W16 compared to NL rats. Hepatic 5alphaR1 and 5betaR expression was higher in SL compared to NL rats after weaning until W6, whereupon expression decreased in the SL rats and remained similar to that in NL rats. In conclusion, small litter rearing in rats induced peripheral tissue-specific alterations in 11beta-HSD1 expression and activity and 5alphaR1 and 5betaR expression during puberty, which could contribute to elevated tissue-specific GC exposure and aggravate the development of metabolic dysregulation in adults. PMID- 22073142 TI - Frequency and associated factors for care giving among elderly patients visiting a teaching hospital in Karachi, Pakistan. AB - OBJECTIVE: To study frequency and associated factors for care giving among elderly patients visiting a teaching hospital in Karachi, Pakistan. METHODOLOGY: A cross sectional questionnaire-based study was conducted at the Community Health Centre (CHC), Aga Khan University Hospital (AKUH) Karachi, Pakistan from September to November 2009. All individuals, visiting the CHC and aged 65 years or above were interviewed after taking written informed consent. RESULTS: A total of 400 elderly completed the interview. Majority were females, 65-69 years age, More than half of the individuals ie: 227 (85%) had received Care Giver experience for assistance and among these 195(72%) had care provided by an immediate family member. A large proportion of them stated that their Care Givers managed to provide less than four hours in a day for care giving. Around 37% showed substantial improvement in their relationship with the care givers. About 70% of the respondents stated that the care provided by the Care Giver improved their quality of life. CONCLUSION: Elderly care is provided by majority of the family members resulting in increased satisfaction level, however small number still not satisfied due to unfulfilled need of these older people. This demands that efforts should be made to strengthen the family support by increasing awareness regarding elderly care and arranging support system by the government. PMID- 22073141 TI - Differentiation between vergence and saccadic functional activity within the human frontal eye fields and midbrain revealed through fMRI. AB - PURPOSE: Eye movement research has traditionally studied solely saccade and/or vergence eye movements by isolating these systems within a laboratory setting. While the neural correlates of saccadic eye movements are established, few studies have quantified the functional activity of vergence eye movements using fMRI. This study mapped the neural substrates of vergence eye movements and compared them to saccades to elucidate the spatial commonality and differentiation between these systems. METHODOLOGY: The stimulus was presented in a block design where the 'off' stimulus was a sustained fixation and the 'on' stimulus was random vergence or saccadic eye movements. Data were collected with a 3T scanner. A general linear model (GLM) was used in conjunction with cluster size to determine significantly active regions. A paired t-test of the GLM beta weight coefficients was computed between the saccade and vergence functional activities to test the hypothesis that vergence and saccadic stimulation would have spatial differentiation in addition to shared neural substrates. RESULTS: Segregated functional activation was observed within the frontal eye fields where a portion of the functional activity from the vergence task was located anterior to the saccadic functional activity (z>2.3; p<0.03). An area within the midbrain was significantly correlated with the experimental design for the vergence but not the saccade data set. Similar functional activation was observed within the following regions of interest: the supplementary eye field, dorsolateral prefrontal cortex, ventral lateral prefrontal cortex, lateral intraparietal area, cuneus, precuneus, anterior and posterior cingulates, and cerebellar vermis. The functional activity from these regions was not different between the vergence and saccade data sets assessed by analyzing the beta weights of the paired t-test (p>0.2). CONCLUSION: Functional MRI can elucidate the differences between the vergence and saccade neural substrates within the frontal eye fields and midbrain. PMID- 22073144 TI - Drosophila TRPA channel painless inhibits male-male courtship behavior through modulating olfactory sensation. AB - The Drosophila melanogaster TRPA family member painless, expressed in a subset of multidendritic neurons embeding in the larval epidermis, is necessary for larval nociception of noxious heat or mechanical stimuli. However, the function of painless in adult flies remains largely unknown. Here we report that mutation of painless leads to a defect in male-male courtship behavior and alteration in olfaction sensitivity in adult flies. Specific downregulation of the expression of the Painless protein in the olfactory projection neurons (PNs) of the antennal lobes (ALs) resulted in a phenotype resembling that found in painless mutant flies, whereas overexpression of Painless in PNs of painless mutant males suppressed male-male courtship behavior. The downregulation of Painless exclusively during adulthood also resulted in male-male courtship behavior. In addition, mutation of the painless gene in flies caused changes in olfaction, suggesting a role for this gene in olfactory processing. These results indicate that functions of painless in the adult central nervous system of Drosophila include modulation of olfactory processing and inhibition of male-male courtship behavior. PMID- 22073143 TI - Serine biosynthesis with one carbon catabolism and the glycine cleavage system represents a novel pathway for ATP generation. AB - Previous experimental evidence indicates that some cancer cells have an alternative glycolysis pathway with net zero ATP production, implying that upregulation of glycolysis in these cells may not be related to the generation of ATP. Here we use a genome-scale model of human cell metabolism to investigate the potential metabolic alterations in cells using net zero ATP glycolysis. We uncover a novel pathway for ATP generation that involves reactions from serine biosynthesis, one-carbon metabolism and the glycine cleavage system, and show that the pathway is transcriptionally upregulated in an inducible murine model of Myc-driven liver tumorigenesis. This pathway has a predicted two-fold higher flux rate in cells using net zero ATP glycolysis than those using standard glycolysis and generates twice as much ATP with significantly lower rate of lactate - but higher rate of alanine secretion. Thus, in cells using the standard - or the net zero ATP glycolysis pathways a significant portion of the glycolysis flux is always associated with ATP generation, and the ratio between the flux rates of the two pathways determines the rate of ATP generation and lactate and alanine secretion during glycolysis. PMID- 22073145 TI - Changes in CRH and ACTH synthesis during experimental and human septic shock. AB - CONTEXT: The mechanisms of septic shock-associated adrenal insufficiency remain unclear. This study aimed at investigating the synthesis of corticotropin releasing hormone (CRH) and vasopressin (AVP) by parvocellular neurons and the antehypophyseal expression of ACTH in human septic shock and in an experimental model of sepsis. OBJECTIVE: To test the hypothesis that ACTH secretion is decreased secondarily to alteration of CRH or AVP synthesis, we undertook a neuropathological study of the antehypophyseal system in patients who had died from septic shock and rats with experimental faecal peritonitis. METHODS: Brains obtained in 9 septic shock patients were compared to 10 nonseptic patients (controls). Parvocellular expression of AVP and CRH mRNA were evaluated by in situ hybridization. Antehypophyseal expression of ACTH, vasopressin V1b and CRH R1 receptors and parvocellular expression of iNOS in the PVN were evaluated by immunohistochemistry. The same experiments were carried out in a fecal peritonitis-induced model of sepsis. Data from septic rats with (n = 6) or without (n = 10) early death were compared to sham-operated (n = 8) animals. RESULTS: In patients and rats, septic shock was associated with a decreased expression of ACTH, unchanged expression of V1B receptor, CRHR1 and AVP mRNA, and increased expression of parvocellular iNOS compared to controls. Septic shock was also characterized by an increased expression of CRH mRNA in rats but not in patients, who notably had a greater duration of septic shock. CONCLUSION: The present study suggests that in humans and in rats, septic shock is associated with decreased ACTH synthesis that is not compensated by its two natural secretagogues, AVP and CRH. One underlying mechanism might be increased expression of iNOS in hypothalamic parvocellular neurons. PMID- 22073146 TI - Effects of vitamin D supplementation on cognitive and emotional functioning in young adults--a randomised controlled trial. AB - BACKGROUND: Epidemiological research links vitamin D status to various brain related outcomes. However, few trials examine whether supplementation can improve such outcomes and none have examined effects on cognition. This study examined whether Vitamin D supplementation led to improvements in diverse measures of cognitive and emotional functioning, and hypothesised that supplementation would lead to improvements in these outcomes compared to placebo. METHODS/PRINCIPAL FINDINGS: Healthy young adults were recruited to a parallel-arm, double-blind trial conducted at The University of Queensland. Participants were randomly allocated to receive Vitamin D (one capsule daily, containing 5000 IU cholecalciferol) or identical placebo capsule for six weeks. All participants and outcome assessors were blinded to group assignment. Primary outcome measures assessed at baseline and 6 weeks were working memory, response inhibition and cognitive flexibility. Secondary outcomes were: hallucination-proneness, psychotic-like experiences, and ratings of depression, anxiety and anger. 128 participants were recruited, randomised and included in primary analyses (vitamin D n = 63; placebo n = 65). Despite significant increases in vitamin D status in the active group, no significant changes were observed in working memory (F = 1.09; p = 0.30), response inhibition (F = 0.82; p = 0.37), cognitive flexibility (F = 1.37; p = 0.24) or secondary outcomes. No serious adverse effects were reported. CONCLUSIONS: Our findings indicate that vitamin D supplementation does not influence cognitive or emotional functioning in healthy young adults. Future controlled trials in targeted populations of interest are required to determine whether supplementation can improve functioning in these domains. Australian and New Zealand Clinical Trials Registry; ACTRN12610000318088. PMID- 22073147 TI - Changes in culture expanded human amniotic epithelial cells: implications for potential therapeutic applications. AB - Human amniotic epithelial cells (hAEC) isolated from term placenta have stem cell like properties, differentiate into tissue specific cells and reduce lung and liver inflammation and fibrosis following transplantation into disease models established in mice. These features together with their low immunogenicity and immunosuppressive properties make hAEC an attractive source of cells for potential therapeutic applications. However, generation of large cell numbers required for therapies through serial expansion in xenobiotic-free media may be a limiting factor. We investigated if hAEC could be expanded in xenobiotic-free media and if expansion altered their differentiation capacity, immunophenotype, immunosuppressive properties and production of immunomodulatory factors. Serial expansion in xenobiotic-free media was limited with cumulative cell numbers and population doubling times significantly lower than controls maintained in fetal calf serum. The epithelial morphology of primary hAEC changed into mesenchymal stromal like cells by passage 4-5 (P4-P5) with down regulation of epithelial markers CK7, CD49f, EpCAM and E-cadherin and elevation of mesenchymal-stromal markers CD44, CD105, CD146 and vimentin. The P5 hAEC expanded in xenobiotic-free medium differentiated into osteocyte and alveolar epithelium-like cells, but not chondrocyte, hepatocyte, alpha- and beta-pancreatic-like cells. Expression of HLA Class IA, Class II and co-stimulatory molecules CD80, CD86 and CD40 remained unaltered. The P5 hAEC suppressed mitogen stimulated T cell proliferation, but were less suppressive compared with primary hAEC at higher splenocyte ratios. Primary and P5 hAEC did not secrete the immunosuppressive factors IL-10 and HGF, whereas TGF-beta1 and HLA-G were reduced and IL-6 elevated in P5 hAEC. These findings suggest that primary and expanded hAEC may be suitable for different cellular therapeutic applications. PMID- 22073148 TI - Occupancy classification of position weight matrix-inferred transcription factor binding sites. AB - BACKGROUND: Computational prediction of Transcription Factor Binding Sites (TFBS) from sequence data alone is difficult and error-prone. Machine learning techniques utilizing additional environmental information about a predicted binding site (such as distances from the site to particular chromatin features) to determine its occupancy/functionality class show promise as methods to achieve more accurate prediction of true TFBS in silico. We evaluate the Bayesian Network (BN) and Support Vector Machine (SVM) machine learning techniques on four distinct TFBS data sets and analyze their performance. We describe the features that are most useful for classification and contrast and compare these feature sets between the factors. RESULTS: Our results demonstrate good performance of classifiers both on TFBS for transcription factors used for initial training and for TFBS for other factors in cross-classification experiments. We find that distances to chromatin modifications (specifically, histone modification islands) as well as distances between such modifications to be effective predictors of TFBS occupancy, though the impact of individual predictors is largely TF specific. In our experiments, Bayesian network classifiers outperform SVM classifiers. CONCLUSIONS: Our results demonstrate good performance of machine learning techniques on the problem of occupancy classification, and demonstrate that effective classification can be achieved using distances to chromatin features. We additionally demonstrate that cross-classification of TFBS is possible, suggesting the possibility of constructing a generalizable occupancy classifier capable of handling TFBS for many different transcription factors. PMID- 22073149 TI - Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization. AB - BACKGROUND: Scintillation camera imaging is used for treatment planning and post treatment dosimetry in liver radioembolization (RE). In yttrium-90 (90Y) RE, scintigraphic images of technetium-99m (99mTc) are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium 166 (166Ho) RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared. METHODOLOGY/PRINCIPAL FINDINGS: Phantom experiments were performed in line with NEMA guidelines to assess the spatial resolution, sensitivity, count rate linearity, and contrast recovery of 99mTc, 90Y and 166Ho. In addition, Monte Carlo simulations were performed to obtain detailed information about the history of detected photons. The results showed that the use of a broad energy window and the high-energy collimator gave optimal combination of sensitivity, spatial resolution, and primary photon fraction for 90Y Bremsstrahlung imaging, although differences with the medium-energy collimator were small. For 166Ho, the high-energy collimator also slightly outperformed the medium-energy collimator. In comparison with 99mTc, the image quality of both 90Y and 166Ho is degraded by a lower spatial resolution, a lower sensitivity, and larger scatter and collimator penetration fractions. CONCLUSIONS/SIGNIFICANCE: The quantitative evaluation of the scintillation camera characteristics presented in this study helps to optimize acquisition parameters and supports future analysis of clinical comparisons between RE studies. PMID- 22073150 TI - Stereo-selectivity of human serum albumin to enantiomeric and isoelectronic pollutants dissected by spectroscopy, calorimetry and bioinformatics. AB - 1-naphthol (1N), 2-naphthol (2N) and 8-quinolinol (8H) are general water pollutants. 1N and 2N are the configurational enantiomers and 8H is isoelectronic to 1N and 2N. These pollutants when ingested are transported in the blood by proteins like human serum albumin (HSA). Binding of these pollutants to HSA has been explored to elucidate the specific selectivity of molecular recognition by this multiligand binding protein. The association constants (K(b)) of these pollutants to HSA were moderate (10(4)-10(5) M(-1)). The proximity of the ligands to HSA is also revealed by their average binding distance, r, which is estimated to be in the range of 4.39-5.37 nm. The binding free energy (DeltaG) in each case remains effectively the same for each site because of enthalpy-entropy compensation (EEC). The difference observed between DeltaC(p) (exp) and DeltaC(p) (calc) are suggested to be caused by binding-induced flexibility changes in the HSA. Efforts are also made to elaborate the differences observed in binding isotherms obtained through multiple approaches of calorimetry, spectroscopy and bioinformatics. We suggest that difference in dissociation constants of pollutants by calorimetry, spectroscopic and computational approaches could correspond to occurrence of different set of populations of pollutants having different molecular characteristics in ground state and excited state. Furthermore, our observation of enhanced binding of pollutants (2N and 8H) in the presence of hemin signifies that ligands like hemin may enhance the storage period of these pollutants in blood that may even facilitate the ill effects of these pollutants. PMID- 22073151 TI - Rapid typing of Coxiella burnetii. AB - Coxiella burnetii has the potential to cause serious disease and is highly prevalent in the environment. Despite this, epidemiological data are sparse and isolate collections are typically small, rare, and difficult to share among laboratories as this pathogen is governed by select agent rules and fastidious to culture. With the advent of whole genome sequencing, some of this knowledge gap has been overcome by the development of genotyping schemes, however many of these methods are cumbersome and not readily transferable between institutions. As comparisons of the few existing collections can dramatically increase our knowledge of the evolution and phylogeography of the species, we aimed to facilitate such comparisons by extracting SNP signatures from past genotyping efforts and then incorporated these signatures into assays that quickly and easily define genotypes and phylogenetic groups. We found 91 polymorphisms (SNPs and indels) among multispacer sequence typing (MST) loci and designed 14 SNP based assays that could be used to type samples based on previously established phylogenetic groups. These assays are rapid, inexpensive, real-time PCR assays whose results are unambiguous. Data from these assays allowed us to assign 43 previously untyped isolates to established genotypes and genomic groups. Furthermore, genotyping results based on assays from the signatures provided here are easily transferred between institutions, readily interpreted phylogenetically and simple to adapt to new genotyping technologies. PMID- 22073152 TI - Predicting in vivo anti-hepatofibrotic drug efficacy based on in vitro high content analysis. AB - BACKGROUND/AIMS: Many anti-fibrotic drugs with high in vitro efficacies fail to produce significant effects in vivo. The aim of this work is to use a statistical approach to design a numerical predictor that correlates better with in vivo outcomes. METHODS: High-content analysis (HCA) was performed with 49 drugs on hepatic stellate cells (HSCs) LX-2 stained with 10 fibrotic markers. ~0.3 billion feature values from all cells in >150,000 images were quantified to reflect the drug effects. A systematic literature search on the in vivo effects of all 49 drugs on hepatofibrotic rats yields 28 papers with histological scores. The in vivo and in vitro datasets were used to compute a single efficacy predictor (E(predict)). RESULTS: We used in vivo data from one context (CCl(4) rats with drug treatments) to optimize the computation of E(predict). This optimized relationship was independently validated using in vivo data from two different contexts (treatment of DMN rats and prevention of CCl(4) induction). A linear in vitro-in vivo correlation was consistently observed in all the three contexts. We used E(predict) values to cluster drugs according to efficacy; and found that high-efficacy drugs tended to target proliferation, apoptosis and contractility of HSCs. CONCLUSIONS: The E(predict) statistic, based on a prioritized combination of in vitro features, provides a better correlation between in vitro and in vivo drug response than any of the traditional in vitro markers considered. PMID- 22073153 TI - A novel small molecule 1,2,3,4,6-penta-O-galloyl-alpha-D-glucopyranose mimics the antiplatelet actions of insulin. AB - BACKGROUND: We have shown that 1,2,3,4,6-penta-O-galloyl-alpha-D-glucopyranose (alpha-PGG), an orally effective hypoglycemic small molecule, binds to insulin receptors and activates insulin-mediated glucose transport. Insulin has been shown to bind to its receptors on platelets and inhibit platelet activation. In this study we tested our hypothesis that if insulin possesses anti-platelet properties then insulin mimetic small molecules should mimic antiplatelet actions of insulin. PRINCIPAL FINDINGS: Incubation of human platelets with insulin or alpha-PGG induced phosphorylation of insulin receptors and IRS-1 and blocked ADP or collagen induced aggregation. Pre-treatment of platelets with alpha-PGG inhibited thrombin-induced release of P-selectin, secretion of ATP and aggregation. Addition of ADP or thrombin to platelets significantly decreased the basal cyclic AMP levels. Pre-incubation of platelets with alpha-PGG blocked ADP or thrombin induced decrease in platelet cyclic AMP levels but did not alter the basal or PGE(1) induced increase in cAMP levels. Addition of alpha-PGG to platelets blocked agonist induced rise in platelet cytosolic calcium and phosphorylation of Akt. Administration of alpha-PGG (20 mg kg(-1)) to wild type mice blocked ex vivo platelet aggregation induced by ADP or collagen. CONCLUSIONS: These data suggest that alpha-PGG inhibits platelet activation, at least in part, by inducing phosphorylation of insulin receptors leading to inhibition of agonist induced: (a) decrease in cyclic AMP; (b) rise in cytosolic calcium; and (c) phosphorylation of Akt. These findings taken together with our earlier reports that alpha-PGG mimics insulin signaling suggest that inhibition of platelet activation by alpha-PGG mimics antiplatelet actions of insulin. PMID- 22073155 TI - Health centre surveys as a potential tool for monitoring malaria epidemiology by area and over time. AB - BACKGROUND: Presently, many malaria control programmes use health facility data to evaluate the impact of their interventions. Facility-based malaria data, although useful, have problems with completeness, validity and representativeness and reliance on routinely collected health facility data might undermine demonstration of the magnitude of the impact of the recent scaleups of malaria interventions. To determine whether carefully conducted health centre surveys can be reliable means of monitoring area specific malaria epidemiology, we have compared malaria specific indices obtained from surveys in health centres with indices obtained from cross-sectional surveys conducted in their catchment communities. METHODS: A series of age stratified, seasonal, cross-sectional surveys were conducted during the peak malaria transmission season in 2008 and during the following dry season in 2009 in six ecologically diverse areas in The Gambia. Participants were patients who attended the health centres plus a representative sample from the catchment villages of these health facilities. Parasitaemia, anaemia, attributable proportion of fever and anti-MSP1-(19) antibody seroprevalence were compared in the health facility attendees and community participants. RESULTS: A total of 16,230 subjects completed the study; approximately half participated in the health centre surveys and half in the wet season surveys. Data from both the health centre and community surveys showed that malaria endemicity in The Gambia is now low, heterogeneous and seasonal. In the wet season, parasitaemia, seroprevalence and fever prevalence were higher in subjects seen in the health centres than in the community surveys. Age patterns of parasitaemia, attributable proportions of fever and seroprevalence rates were similar in subjects who participated in the community and health centre surveys. CONCLUSION: Health centre surveys have potential as a surveillance tool for evaluating area specific malaria control activities and for monitoring changes in local malaria epidemiology over time. PMID- 22073154 TI - Selenium and lung cancer: a systematic review and meta analysis. AB - BACKGROUND: Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies. METHODS AND FINDINGS: Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serum<106 ng/mL), but increase risk of lung cancers in those with higher selenium (>= 121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61-1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70-3.24); and all-cause-death, OR 0.93 (95%CI 0.79-1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy. CONCLUSIONS: Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context. PMID- 22073156 TI - Association of low level viremia with inflammation and mortality in HIV-infected adults. AB - BACKGROUND: Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear. METHODS: The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected"), 1-19, 20 399, 400-9999, and >= 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors. RESULTS: HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA >= 10,000 copies/ml was associated with 89% higher IL-6 (p<0.001). This association was attenuated by ~50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA >= 10,000 copies/ml). Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation. CONCLUSION: HIV RNA >= 10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years. PMID- 22073157 TI - Empirical models of transitions between coral reef states: effects of region, protection, and environmental change. AB - There has been substantial recent change in coral reef communities. To date, most analyses have focussed on static patterns or changes in single variables such as coral cover. However, little is known about how community-level changes occur at large spatial scales. Here, we develop Markov models of annual changes in coral and macroalgal cover in the Caribbean and Great Barrier Reef (GBR) regions. We analyzed reef surveys from the Caribbean and GBR (1996-2006). We defined a set of reef states distinguished by coral and macroalgal cover, and obtained Bayesian estimates of the annual probabilities of transitions between these states. The Caribbean and GBR had different transition probabilities, and therefore different rates of change in reef condition. This could be due to differences in species composition, management or the nature and extent of disturbances between these regions. We then estimated equilibrium probability distributions for reef states, and coral and macroalgal cover under constant environmental conditions. In both regions, the current distributions are close to equilibrium. In the Caribbean, coral cover is much lower and macroalgal cover is higher at equilibrium than in the GBR. We found no evidence for differences in transition probabilities between the first and second halves of our survey period, or between Caribbean reefs inside and outside marine protected areas. However, our power to detect such differences may have been low. We also examined the effects of altering transition probabilities on the community state equilibrium, along a continuum from unfavourable (e.g., increased sea surface temperature) to favourable (e.g., improved management) conditions. Both regions showed similar qualitative responses, but different patterns of uncertainty. In the Caribbean, uncertainty was greatest about effects of favourable changes, while in the GBR, we are most uncertain about effects of unfavourable changes. Our approach could be extended to provide risk analysis for management decisions. PMID- 22073158 TI - Multiple geographic origins of commensalism and complex dispersal history of Black Rats. AB - The Black Rat (Rattus rattus) spread out of Asia to become one of the world's worst agricultural and urban pests, and a reservoir or vector of numerous zoonotic diseases, including the devastating plague. Despite the global scale and inestimable cost of their impacts on both human livelihoods and natural ecosystems, little is known of the global genetic diversity of Black Rats, the timing and directions of their historical dispersals, and the risks associated with contemporary movements. We surveyed mitochondrial DNA of Black Rats collected across their global range as a first step towards obtaining an historical genetic perspective on this socioeconomically important group of rodents. We found a strong phylogeographic pattern with well-differentiated lineages of Black Rats native to South Asia, the Himalayan region, southern Indochina, and northern Indochina to East Asia, and a diversification that probably commenced in the early Middle Pleistocene. We also identified two other currently recognised species of Rattus as potential derivatives of a paraphyletic R. rattus. Three of the four phylogenetic lineage units within R. rattus show clear genetic signatures of major population expansion in prehistoric times, and the distribution of particular haplogroups mirrors archaeologically and historically documented patterns of human dispersal and trade. Commensalism clearly arose multiple times in R. rattus and in widely separated geographic regions, and this may account for apparent regionalism in their associated pathogens. Our findings represent an important step towards deeper understanding the complex and influential relationship that has developed between Black Rats and humans, and invite a thorough re-examination of host-pathogen associations among Black Rats. PMID- 22073159 TI - Impact of changing drug treatment and malaria endemicity on the heritability of malaria phenotypes in a longitudinal family-based cohort study. AB - Despite considerable success of genome wide association (GWA) studies in identifying causal variants for many human diseases, their success in unraveling the genetic basis to complex diseases has been more mitigated. Pathogen population structure may impact upon the infectious phenotype, especially with the intense short-term selective pressure that drug treatment exerts on pathogens. Rigorous analysis that accounts for repeated measures and disentangles the influence of genetic and environmental factors must be performed. Attempts should be made to consider whether pathogen diversity will impact upon host genetic responses to infection.We analyzed the heritability of two Plasmodium falciparum phenotypes, the number of clinical malaria episodes (PFA) and the proportion of these episodes positive for gametocytes (Pfgam), in a family-based cohort followed for 19 years, during which time there were four successive drug treatment regimes, with documented appearance of drug resistance. Repeated measures and variance components analyses were performed with fixed environmental, additive genetic, intra-individual and maternal effects for each drug period. Whilst there was a significant additive genetic effect underlying PFA during the first drug period of study, this was lost in subsequent periods. There was no additive genetic effect for Pfgam. The intra-individual effect increased significantly in the chloroquine period.The loss of an additive genetic effect following novel drug treatment may result in significant loss of power to detect genes in a GWA study. Prior genetic analysis must be a pre-requisite for more detailed GWA studies. The temporal changes in the individual genetic and the intra-individual estimates are consistent with those expected if there were specific host-parasite interactions. The complex basis to the human response to malaria parasite infection likely includes dominance/epistatic genetic effects encompassed within the intra-individual variance component. Evaluating their role in influencing the outcome of infection through host genotype by parasite genotype interactions warrants research effort. PMID- 22073160 TI - Evolutionary instability of symbiotic function in Bradyrhizobium japonicum. AB - Bacterial mutualists are often acquired from the environment by eukaryotic hosts. However, both theory and empirical work suggest that this bacterial lifestyle is evolutionarily unstable. Bacterial evolution outside of the host is predicted to favor traits that promote an independent lifestyle in the environment at a cost to symbiotic function. Consistent with these predictions, environmentally acquired bacterial mutualists often lose symbiotic function over evolutionary time. Here, we investigate the evolutionary erosion of symbiotic traits in Bradyrhizobium japonicum, a nodulating root symbiont of legumes. Building on a previous published phylogeny we infer loss events of nodulation capability in a natural population of Bradyrhizobium, potentially driven by mutation or deletion of symbiosis loci. Subsequently, we experimentally evolved representative strains from the symbiont population under host-free in vitro conditions to examine potential drivers of these loss events. Among Bradyrhizobium genotypes that evolved significant increases in fitness in vitro, two exhibited reduced symbiotic quality, but no experimentally evolved strain lost nodulation capability or evolved any fixed changes at six sequenced loci. Our results are consistent with trade-offs between symbiotic quality and fitness in a host free environment. However, the drivers of loss-of-nodulation events in natural Bradyrhizobium populations remain unknown. PMID- 22073161 TI - Autonomic modulation and health-related quality of life among schizophrenic patients treated with non-intensive case management. AB - BACKGROUND: Schizophrenia is associated with autonomic dysfunction and this may increase cardiovascular mortality. Past studies on autonomic modulation of schizophrenic patients focused on inpatients rather than individuals in a community setting, especially those receiving non-intensive case management (non ICM). Besides, autonomic modulation and its association with health-related quality of life (HRQoL) in this population remain unexplored. METHODS: A total of 25 schizophrenic patients treated by non-ICM and 40 healthy volunteers were matched by age, gender and body mass index; smokers were excluded. Between the two groups, we compared the individuals' 5 min resting assessments of heart rate variability and their HRQoL, which was measured using EuroQoL-5D (EQ-5D). Patients with schizophrenia were assessed for psychopathology using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). We examined the relationship between heart rate variability measurements, HRQoL scores, PANSS scores, and other clinical variables among the schizophrenic patients treated by non-ICM. RESULTS: Compared to the controls, patients with schizophrenia showed a significant impairment of autonomic modulation and a worse HRQoL. Cardiovagal dysfunction among the schizophrenic patients could be predicted independently based on lower educational level and more negative symptoms. Sympathetic predominance was directly associated with anticholinergics use and EQ-5D using a visual analogue scale (EQ-VAS). CONCLUSION: Patients with schizophrenia treated by non-ICM show a significant impairment of their autonomic function and HRQoL compared to the controls. Since the sympathovagal dysfunction is associated with more negative symptoms or higher VAS score, the treatment of the negative symptoms as well as the monitoring of HRQoL might help to manage cardiovascular risk among these individuals. In addition, EQ-VAS scores must be interpreted more cautiously in such a population. PMID- 22073162 TI - Xenon pretreatment may prevent early memory decline after isoflurane anesthesia and surgery in mice. AB - Postoperative cognitive decline (POCD) is a common complication following surgery, but its aetiology remains unclear. We hypothesized that xenon pretreatment prevents POCD by suppressing the systemic inflammatory response or through an associated protective signaling pathway involving heat shock protein 72 (Hsp72) and PI3-kinase. Twenty-four hours after establishing long-term memory using fear conditioning training, C57BL/6 adult male mice (n = 12/group) received one of the following treatments: 1) no treatment group (control); 2) 1.8% isoflurane anesthesia; 3) 70% xenon anesthesia; 4) 1.8% isoflurane anesthesia with surgery of the right hind leg tibia that was pinned and fractured; or 5) pretreatment with 70% xenon for 20 minutes followed immediately by 1.8% isoflurane anesthesia with the surgery described above. Assessments of hippocampal-dependent memory were performed on days 1 and 7 after treatment. Hsp72 and PI3-kinase in hippocampus, and plasma IL-1beta, were measured using western blotting and ELISA respectively, from different cohorts on day 1 after surgery. Isoflurane induced memory deficit after surgery was attenuated by xenon pretreatment. Xenon pretreatment prevented the memory deficit typically seen on day 1 (P = 0.04) but not on day 7 (P = 0.69) after surgery under isoflurane anesthesia, when compared with animals that underwent surgery without pretreatment. Xenon pretreatment modulated the expression of Hsp72 (P = 0.054) but had no significant effect on PI3-kinase (P = 0.54), when compared to control. Xenon pretreatment also reduced the plasma level increase of IL-1beta induced by surgery (P = 0.028). Our data indicated that surgery and/or Isoflurane induced memory deficit was attenuated by xenon pretreatment. This was associated with a reduction in the plasma level of IL-1beta and an upregulation of Hsp72 in the hippocampus. PMID- 22073163 TI - Designer TGFbeta superfamily ligands with diversified functionality. AB - Transforming Growth Factor--beta (TGFbeta) superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs), and Bone Morphogenetic Proteins (BMPs), are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer), to engineer chemically-refoldable TGFbeta superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-betaA and BMP-2 sequences, exhibits the refolding characteristics of BMP 2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFbeta superfamily ligands through development of novel chimeric TGFbeta ligands with diverse biological and clinical values. PMID- 22073164 TI - Acute overactive endocannabinoid signaling induces glucose intolerance, hepatic steatosis, and novel cannabinoid receptor 1 responsive genes. AB - Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1). Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP), perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG) and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251) and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control), IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2), which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50%) the majority (303 of 533) of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1 dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and identify novel cannabinoid responsive genes. PMID- 22073165 TI - The ghosts in the computer: the role of agency and animacy attributions in "ghost controls". AB - Three studies evaluated the role of 4-year-old children's agency- and animacy attributions when learning from a computerized ghost control (GC). In GCs, participants observe events occurring without an apparent agent, as if executed by a "ghost" or unobserved causal forces. Using a touch-screen, children in Experiment 1 responded to three pictures in a specific order under three learning conditions: (i) trial-and-error (Baseline), (ii) imitation and (iii) Ghost Control. Before testing in the GC, children were read one of three scripts that determined agency attributions. Post-test assessments confirmed that all children attributed agency to the computer and learned in all GCs. In Experiment 2, children were not trained on the computer prior to testing, and no scripts were used. Three different GCs, varying in number of agency cues, were used. Children failed to learn in these GCs, yet attributed agency and animacy to the computer. Experiment 3 evaluated whether children could learn from a human model in the absence of training under conditions where the information presented by the model and the computer was either consistent or inconsistent. Children evidenced learning in both of these conditions. Overall, learning in social conditions (Exp. 3) was significantly better than learning in GCs (Exp. 2). These results, together with other published research, suggest that children privilege social over non-social sources of information and are generally more adept at learning novel tasks from a human than from a computer or GC. PMID- 22073166 TI - Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells. AB - Natural killer T (NKT) cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo)) and mature (NK1.1(hi)) cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder)), that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT?T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells. PMID- 22073167 TI - Computation emerges from adaptive synchronization of networking neurons. AB - The activity of networking neurons is largely characterized by the alternation of synchronous and asynchronous spiking sequences. One of the most relevant challenges that scientists are facing today is, then, relating that evidence with the fundamental mechanisms through which the brain computes and processes information, as well as with the arousal (or progress) of a number of neurological illnesses. In other words, the problem is how to associate an organized dynamics of interacting neural assemblies to a computational task. Here we show that computation can be seen as a feature emerging from the collective dynamics of an ensemble of networking neurons, which interact by means of adaptive dynamical connections. Namely, by associating logical states to synchronous neuron's dynamics, we show how the usual Boolean logics can be fully recovered, and a universal Turing machine can be constructed. Furthermore, we show that, besides the static binary gates, a wider class of logical operations can be efficiently constructed as the fundamental computational elements interact within an adaptive network, each operation being represented by a specific motif. Our approach qualitatively differs from the past attempts to encode information and compute with complex systems, where computation was instead the consequence of the application of control loops enforcing a desired state into the specific system's dynamics. Being the result of an emergent process, the computation mechanism here described is not limited to a binary Boolean logic, but it can involve a much larger number of states. As such, our results can enlighten new concepts for the understanding of the real computing processes taking place in the brain. PMID- 22073168 TI - "Price-quakes" shaking the world's stock exchanges. AB - BACKGROUND: Systemic risk has received much more awareness after the excessive risk taking by major financial instituations pushed the world's financial system into what many considered a state of near systemic failure in 2008. The IMF for example in its yearly 2009 Global Financial Stability Report acknowledged the lack of proper tools and research on the topic. Understanding how disruptions can propagate across financial markets is therefore of utmost importance. METHODOLOGY/PRINCIPAL FINDINGS: Here, we use empirical data to show that the world's markets have a non-linear threshold response to events, consistent with the hypothesis that traders exhibit change blindness. Change blindness is the tendency of humans to ignore small changes and to react disproportionately to large events. As we show, this may be responsible for generating cascading events -pricequakes--in the world's markets. We propose a network model of the world's stock exchanges that predicts how an individual stock exchange should be priced in terms of the performance of the global market of exchanges, but with change blindness included in the pricing. The model has a direct correspondence to models of earth tectonic plate movements developed in physics to describe the slip-stick movement of blocks linked via spring forces. CONCLUSIONS/SIGNIFICANCE: We have shown how the price dynamics of the world's stock exchanges follows a dynamics of build-up and release of stress, similar to earthquakes. The nonlinear response allows us to classify price movements of a given stock index as either being generated internally, due to specific economic news for the country in question, or externally, by the ensemble of the world's stock exchanges reacting together like a complex system. The model may provide new insight into the origins and thereby also prevent systemic risks in the global financial network. PMID- 22073169 TI - Divergent changes in plant community composition under 3-decade grazing exclusion in continental steppe. AB - An understanding of the factors controlling plant community composition will allow improved prediction of the responses of plant communities to natural and anthropogenic environmental change. Using monitoring data from 1980 to 2009, we quantified the changes in community composition in Leymus chinensis and Stipa grandis dominated grasslands in Inner Mongolia under long-term grazing-exclusion and free-grazing conditions, respectively. We demonstrated that the practice of long-term grazing exclusion has significant effects on the heterogeneity, the dominant species, and the community composition in the two grasslands. The community composition of L. chinensis and S. grandis grasslands exhibited directional changes with time under long-term grazing exclusion. Under free grazing, the L. chinensis community changed directionally with time, but the pattern of change was stochastic in the S. grandis community. We attributed the divergent responses to long-term grazing exclusion in the S. grandis and L. chinensis grasslands to litter accumulation and changes in the microenvironment after grazing exclusion, which collectively altered the growth and regeneration of the dominant species. The changes in the grazed grasslands were primarily determined by the selective feeding of sheep during long-term heavy grazing. Overall, the responses of the community composition of the Inner Mongolian grasslands to long-term grazing exclusion and heavy grazing were divergent, and depended primarily on the grassland type. Our findings provide new insights into the role of grazing in the maintenance of community structure and function and therefore have important implications for grassland management. PMID- 22073170 TI - An essential farnesylated kinesin in Trypanosoma brucei. AB - Kinesins are a family of motor proteins conserved throughout eukaryotes. In our present study we characterize a novel kinesin, Kinesin(CaaX), orthologs of which are only found in the kinetoplastids and not other eukaryotes. Kinesin(CaaX) has the CVIM amino acids at the C-terminus, and CVIM was previously shown to be an ideal signal for protein farnesylation in T. brucei. In this study we show Kinesin(CaaX) is farnesylated using radiolabeling studies and that farnesylation is dependent on the CVIM motif. Using RNA interference, we show Kinesin(CaaX) is essential for T. brucei proliferation. Additionally RNAi Kinesin(CaaX) depleted T. brucei are 4 fold more sensitive to the protein farneysltransferase (PFT) inhibitor LN-59, suggesting that Kinesin(CaaX) is a target of PFT inhibitors' action to block proliferation of T. brucei. Using tetracycline-induced exogenous tagged Kinesin(CaaX) and Kinesin(CVIMdeletion) (non-farnesylated Kinesin) expression lines in T. brucei, we demonstrate Kinesin(CaaX) is farnesylated in T. brucei cells and this farnesylation has functional effects. In cells expressing a CaaX-deleted version of Kinesin, the localization is more diffuse which suggests correct localization depends on farnesylation. Through our investigation of cell cycle, nucleus and kinetoplast quantitation and immunofluorescence assays an important role is suggested for Kinesin(CaaX) in the separation of nuclei and kinetoplasts during and after they have been replicated. Taken together, our work suggests Kinesin(CaaX) is a target of PFT inhibition of T. brucei cell proliferation and Kinesin(CaaX) functions through both the motor and farnesyl groups. PMID- 22073171 TI - Phenotypic pattern-based assay for dynamically monitoring host cellular responses to Salmonella infections. AB - The interaction between mammalian host cells and bacteria is a dynamic process, and the underlying pathologic mechanisms are poorly characterized. Limited information describing the host-bacterial interaction is based mainly on studies using label-based endpoint assays that detect changes in cell behavior at a given time point, yielding incomplete information. In this paper, a novel, label-free, real-time cell-detection system based on electronic impedance sensor technology was adapted to dynamically monitor the entire process of intestinal epithelial cells response to Salmonella infection. Changes in cell morphology and attachment were quantitatively and continuously recorded following infection. The resulting impedance-based time-dependent cell response profiles (TCRPs) were compared to standard assays and showed good correlation and sensitivity. Biochemical assays further suggested that TCRPs were correlated with cytoskeleton-associated morphological dynamics, which can be largely attenuated by inhibitions of actin and microtubule polymerization. Collectively, our data indicate that cell electrode impedance measurements not only provide a novel, real-time, label-free method for investigating bacterial infection but also help advance our understanding of host responses in a more physiological and continuous manner that is beyond the scope of current endpoint assays. PMID- 22073172 TI - Differences among major taxa in the extent of ecological knowledge across four major ecosystems. AB - Existing knowledge shapes our understanding of ecosystems and is critical for ecosystem-based management of the world's natural resources. Typically this knowledge is biased among taxa, with some taxa far better studied than others, but the extent of this bias is poorly known. In conjunction with the publically available World Registry of Marine Species database (WoRMS) and one of the world's premier electronic scientific literature databases (Web of Science(r)), a text mining approach is used to examine the distribution of existing ecological knowledge among taxa in coral reef, mangrove, seagrass and kelp bed ecosystems. We found that for each of these ecosystems, most research has been limited to a few groups of organisms. While this bias clearly reflects the perceived importance of some taxa as commercially or ecologically valuable, the relative lack of research of other taxonomic groups highlights the problem that some key taxa and associated ecosystem processes they affect may be poorly understood or completely ignored. The approach outlined here could be applied to any type of ecosystem for analyzing previous research effort and identifying knowledge gaps in order to improve ecosystem-based conservation and management. PMID- 22073173 TI - Multiple phenotypes resulting from a mutagenesis screen for pharynx muscle mutations in Caenorhabditis elegans. AB - We describe a novel screen to isolate pharyngeal cell morphology mutants in Caenorhabditis elegans using myo-2::GFP to rapidly identify abnormally shaped pharynxes in EMS (Ethyl Methanesulfonate) mutagenized worms. We observed over 83 C. elegans lines with distinctive pharyngeal phenotypes in worms surviving to the L1 larval stage, with phenotypes ranging from short pharynx, unattached pharynx, missing cells, asymmetric morphology, and non-adherent pharynx cells. Thirteen of these mutations have been chromosomally mapped using Single Nucleotide Polymorphisms (SNPs) and deficiency strain complementation. Our studies have focused on genetically mapping and functionally testing two phenotypes, the short pharynx and the loss of muscle cohesion phenotypes. We have also identified new alleles of sma-1, and our screen suggests many genes directing pharynx assembly and structure may be either pharynx specific or less critical in other tissues. PMID- 22073174 TI - Marital status and mortality among middle age and elderly men and women in urban Shanghai. AB - BACKGROUND: Previous studies have suggested that marital status is associated with mortality, but few studies have been conducted in China where increasing aging population and divorce rates may have major impact on health and total mortality. METHODS: We examined the association of marital status with mortality using data from the Shanghai Women's Health Study (1996-2009) and Shanghai Men's Health Study (2002-2009), two population-based cohort studies of 74,942 women aged 40-70 years and 61,500 men aged 40-74 years at the study enrollment. Deaths were identified by biennial home visits and record linkage with the vital statistics registry. Marital status was categorized as married, never married, divorced, widowed, and all unmarried categories combined. Cox regression models were used to derive hazard ratios (HR) and 95% confidence interval (CI). RESULTS: Unmarried and widowed women had an increased all-cause HR = 1.11, 95% CI: 1.03, 1.21 and HR = 1.10, 95% CI: 1.02, 1.20 respectively) and cancer (HR = 1.17, 95% CI: 1.04, 1.32 and HR = 1.18, 95% CI: 1.04, 1.34 respectively) mortality. Never married women had excess all-cause mortality (HR = 1.46, 95% CI: 1.03, 2.09). Divorce was associated with elevated cardiovascular disease (CVD) mortality in women (HR = 1.47, 95% CI: 1.01, 2.13) and elevated all-cause mortality (HR = 2.45, 95% CI: 1.55, 3.86) in men. Amongst men, not being married was associated with excess all-cause (HR = 1.45, 95% CI: 1.12, 1.88) and CVD (HR = 1.65, 95% CI: 1.07, 2.54) mortality. CONCLUSIONS: Marriage is associated with decreased all cause mortality and CVD mortality, in particular, among both Chinese men and women. PMID- 22073175 TI - Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. AB - After menopause, many women experience vaginal dryness and atrophy of tissue, often attributed to the loss of estrogen. An understudied aspect of vaginal health in women who experience dryness due to atrophy is the role of the resident microbes. It is known that the microbiota has an important role in healthy vaginal homeostasis, including maintaining the pH balance and excluding pathogens. The objectives of this study were twofold: first to identify the microbiome of post-menopausal women with and without vaginal dryness and symptoms of atrophy; and secondly to examine any differences in epithelial gene expression associated with atrophy. The vaginal microbiome of 32 post-menopausal women was profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Sixteen subjects were selected for follow-up sampling every two weeks for 10 weeks. In addition, 10 epithelial RNA samples (6 healthy and 4 experiencing vaginal dryness) were acquired for gene expression analysis by Affymetrix Human Gene array. The microbiota abundance profiles were relatively stable over 10 weeks compared to previously published data on premenopausal women. There was an inverse correlation between Lactobacillus ratio and dryness and an increased bacterial diversity in women experiencing moderate to severe vaginal dryness. In healthy participants, Lactobacillus iners and L. crispatus were generally the most abundant, countering the long-held view that lactobacilli are absent or depleted in menopause. Vaginal dryness and atrophy were associated with down regulation of human genes involved in maintenance of epithelial structure and barrier function, while those associated with inflammation were up-regulated consistent with the adverse clinical presentation. PMID- 22073176 TI - Transcriptional profiling of protein expression related genes of Pichia pastoris under simulated microgravity. AB - The physiological responses and transcription profiling of Pichia pastoris GS115 to simulated microgravity (SMG) were substantially changed compared with normal gravity (NG) control. We previously reported that the recombinant P. pastoris grew faster under SMG than NG during methanol induction phase and the efficiencies of recombinant enzyme production and secretion were enhanced under SMG, which was considered as the consequence of changed transcriptional levels of some key genes. In this work, transcriptiome profiling of P. pastoris cultured under SMG and NG conditions at exponential and stationary phases were determined using next-generation sequencing (NGS) technologies. Four categories of 141 genes function as methanol utilization, protein chaperone, RNA polymerase and protein transportation or secretion classified according to Gene Ontology (GO) were chosen to be analyzed on the basis of NGS results. And 80 significantly changed genes were weighted and estimated by Cluster 3.0. It was found that most genes of methanol metabolism (85% of 20 genes) and protein transportation or secretion (82.2% of 45 genes) were significantly up-regulated under SMG. Furthermore the quantity and fold change of up-regulated genes in exponential phase of each category were higher than those of stationary phase. The results indicate that the up-regulated genes of methanol metabolism and protein transportation or secretion mainly contribute to enhanced production and secretion of the recombinant protein under SMG. PMID- 22073177 TI - A novel dimer-tetramer transition captured by the crystal structure of the HIV-1 Nef. AB - HIV-1 Nef modulates disease progression through interactions with over 30 host proteins. Individual chains fold into membrane-interacting N-terminal and C terminal core (Nef(core)) domains respectively. Nef exists as small oligomers near membranes and associates into higher oligomers such as tetramers or hexadecamers in the cytoplasm. Earlier structures of the Nef(core) in apo and complexed forms with the Fyn-kinase SH3 domain revealed dimeric association details and the role of the conserved PXXP recognition motif (residues 72-78) of Nef in SH3-domain interactions. The crystal structure of the tetrameric Nef reported here corresponds to the elusive cytoplasmic stage. Comparative analyses show that subunits of Nef(core) dimers (open conformation) swing out with a relative displacement of ~22 A and rotation of ~174 degrees to form the 'closed' tetrameric structure. The changes to the association are around Asp125, a conserved residue important for viral replication and the important XR motif (residues 107-108). The tetramer associates through C4 symmetry instead of the 222 symmetry expected when two dimers associate together. This novel dimer tetramer transition agrees with earlier solution studies including small angle X ray scattering, analytical ultracentrifugation, dynamic laser light scattering and our glutaraldehyde cross-linking experiments. Comparisons with the Nef(core)- Fyn-SH3 domain complexes reveal that the PXXP motif that interacts with the SH3 domain in the dimeric form is sterically occluded in the tetramer. However the 151-180 loop that is distal to the PXXP motif and contains several protein interaction motifs remains accessible. The results suggest how changes to the oligomeric state of Nef can help it distinguish between protein partners. PMID- 22073178 TI - Characterization of intrinsically disordered prostate associated gene (PAGE5) at single residue resolution by NMR spectroscopy. AB - BACKGROUND: The Cancer-Testis antigens (CTA) are proteins expressed in human germ line and certain cancer cells. CTAs form a large gene family, representing 10% of X-chromosomal genes. They have high potential for cancer-specific immunotherapy. However, their biological functions are currently unknown. Prostate associated genes (PAGE) are characterized as CTAs. PAGE5 is one of six proteins belonging to this protein family, also called CT16. METHODOLOGY/PRINCIPAL FINDINGS: In this study we show, using bioinformatics, chromatographic and solution state NMR spectroscopic methods, that PAGE5 is an intrinsically disordered protein (IDP). CONCLUSION/SIGNIFICANCE: The study stands out as the first time structural characterization of the PAGE family protein and introduces how solution state NMR spectroscopy can be effectively utilized for identification of molecular recognition regions (MoRF) in IDPs, known often as transiently populated secondary structures. PMID- 22073179 TI - Interleukin-1 as an injury signal mobilizes retinyl esters in hepatic stellate cells through down regulation of lecithin retinol acyltransferase. AB - Retinoids are mostly stored as retinyl esters in hepatic stellate cells (HSCs) through esterification of retinol and fatty acid, catalyzed by lecithin-retinol acyltransferase (LRAT). This study is designated to address how retinyl esters are mobilized in liver injury for tissue repair and wound healing. Initially, we speculated that acute inflammatory cytokines may act as injury signal to mobilize retinyl esters by down-regulation of LRAT in HSCs. By examining a panel of cytokines we found interleukin-1 (IL-1) can potently down-regulate mRNA and protein levels of LRAT, resulting in mobilization of retinyl esters in primary rat HSCs. To simulate the microenvironment in the space of Disse, HSCs were embedded in three-dimensional extracellular matrix, by which HSCs retaine quiescent phenotypes, indicated by up-regulation of LRAT and accumulation of lipid droplets. Upon IL-1 stimulation, LRAT expression went down together with mobilization of lipid droplets. Secreted factors from Kupffer cells were able to suppress LRAT expression in HSCs, which was neutralized by IL-1 receptor antagonist. To explore the underlying mechanism we noted that the stability of LRAT protein is not significantly regulated by IL-1, indicating the regulation is likely at transcriptional level. Indeed, we found that IL-1 failed to down regulate recombinant LRAT protein expressed in HSCs by adenovirus, while transcription of endogenous LRAT was promptly decreased. Following liver damage, IL-1 was promptly elevated in a close pace with down-regulation of LRAT transcription, implying their causative relationship. After administration of IL 1, retinyl ester levels in the liver, as measured by LC/MS/MS, decreased in association with down-regulation of LRAT. Likewise, IL-1 receptor knockout mice were protected from injury-induced down-regulation of LRAT. In summary, we identified IL-1 as an injury signal to mobilize retinyl ester in HSCs through down-regulation of LRAT, implying a mechanism governing transition from hepatic injury to wound healing. PMID- 22073180 TI - Rapid evolution of the mitochondrial genome in Chalcidoid wasps (Hymenoptera: Chalcidoidea) driven by parasitic lifestyles. AB - Among the Chalcidoids, hymenopteran parasitic wasps that have diversified lifestyles, a partial mitochondrial genome has been reported only from Nasonia. This genome had many unusual features, especially a dramatic reorganization and a high rate of evolution. Comparisons based on more mitochondrial genomic data from the same superfamily were required to reveal weather these unusual features are peculiar to Nasonia or not. In the present study, we sequenced the nearly complete mitochondrial genomes from the species Philotrypesis. pilosa and Philotrypesis sp., both of which were associated with Ficus hispida. The acquired data included all of the protein-coding genes, rRNAs, and most of the tRNAs, and in P. pilosa the control region. High levels of nucleotide divergence separated the two species. A comparison of all available hymenopteran mitochondrial genomes (including a submitted partial genome from Ceratosolen solmsi) revealed that the Chalcidoids had dramatic mitochondrial gene rearrangments, involved not only the tRNAs, but also several protein-coding genes. The AT-rich control region was translocated and inverted in Philotrypesis. The mitochondrial genomes also exhibited rapid rates of evolution involving elevated nonsynonymous mutations. PMID- 22073181 TI - A numerical analysis model for interpretation of flow cytometric studies of ex vivo phagocytosis. AB - The study of ex vivo phagocytosis via flow cytometry requires that one distinguish experimentally between uptake and adsorption of fluorescently labeled targets by phagocytes. Removal of the latter quantity from the analysis is the most common means of analyzing such data. Because the probability of phagocytosis is a function of the probability of adsorption, and because partially quenched fluorescence after uptake often overlaps with that of negative controls, this approach is suboptimal at best. Here, we describe a numerical analysis model which overcomes these limitations. We posit that the random adsorption of targets to macrophages, and subsequent phagocytosis, is a function of three parameters: the ratio of targets to macrophages (m), the mean fluorescence intensity imparted to the phagocyte by the internalized target (alpha), and the probability of phagocytosis per adsorbed target (p). The potential values of these parameters define a parameter space and their values at any point in parameter space can be used to predict the fraction of adsorption(+) and [adsorption(-), phagocytosis(+)] cells that might be observed experimentally. By systematically evaluating the points in parameter space for the latter two values and comparing them to experimental data, the model arrives at sets of parameter values that optimally predict such data. Using activated THP-1 cells as macrophages and platelets as targets, we validate the model by demonstrating that it can distinguish between the effects of experimental changes in m, alpha, and p. Finally, we use the model to demonstrate that platelets from a congenitally thrombocytopenic WAS patient show an increased probability of ex vivo phagocytosis. This finding correlates with other evidence that rapid in vivo platelet consumption contributes significantly to the thrombocytopenia of WAS. Our numerical analysis method represents a useful and innovative approach to multivariate analysis. PMID- 22073182 TI - Operational challenges in diagnosing multi-drug resistant TB and initiating treatment in Andhra Pradesh, India. AB - BACKGROUND: Revised National TB Control Programme (RNTCP), Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines. OBJECTIVES: To assess i) using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii) the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii) the number and proportion of those diagnosed as MDR TB who were successfully initiated on treatment. METHODS: A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009. RESULTS: Among 23,999 TB patients registered for treatment there were 559 (2%) MDR-TB suspects (according to programme definition) of which 307 (55%) underwent diagnosis and amongst these 169 (55%) were found to be MDR-TB. Of the MDR-TB patients, 112 (66%) were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services. PMID- 22073183 TI - Visualization of painful experiences believed to trigger the activation of affective and emotional brain regions in subjects with low back pain. AB - In the management of clinical low back pain (LBP), actual damage to lower back areas such as muscles, intervertebral discs etc. are normally targeted for therapy. However, LBP may involve not only sensory pain, but also underlying affective pain which may also play an important role overall in painful events. Therefore we hypothesized that visualization of a painful event may trigger painful memories, thus provoking the affective dimension of pain. The present study investigated neural correlates of affect processing in subjects with LBP (n = 11) and subjects without LBP (n = 11) through the use of virtual LBP stimuli. Whole brain functional magnetic resonance imaging (MRI) was performed for all subjects while they were shown a picture of a man carrying luggage in a half crouching position. All subjects with LBP reported experiencing discomfort and 7 LBP subjects reported experiencing pain. In contrast to subjects without LBP, subjects with LBP displayed activation of the cortical area related to pain and emotions: the insula, supplementary motor area, premotor area, thalamus, pulvinar, posterior cingulate cortex, hippocampus, fusiform, gyrus, and cerebellum. These results suggest that the virtual LBP stimuli caused memory retrieval of unpleasant experiences and therefore may be associated with prolonged chronic LBP conditions. PMID- 22073184 TI - PLGA, PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humoral immunity. AB - Development of vaccines in autoimmune diseases has received wide attention over the last decade. However, many vaccines showed limited clinical efficacy. To enhance vaccine efficacy in infectious diseases, biocompatible and biodegradable polymeric nanoparticles have gained interest as antigen delivery systems. We investigated in mice whether antigen-encapsulated PLGA (poly-lactic-co-glycolic acid), PLGA-TMC (N-trimethyl chitosan) or TMC-TPP (tri-polyphosphate) nanoparticles can also be used to modulate the immunological outcome after nasal vaccination. These three nanoparticles enhanced the antigen presentation by dendritic cells, as shown by increased in vitro and in vivo CD4(+) T-cell proliferation. However, only nasal PLGA nanoparticles were found to induce an immunoregulatory response as shown by enhanced Foxp3 expression in the nasopharynx associated lymphoid tissue and cervical lymph nodes. Nasal administration of OVA-containing PLGA particle resulted in functional suppression of an OVA-specific Th-1 mediated delayed-type hypersensitivity reaction, while TMC-TPP nanoparticles induced humoral immunity, which coincided with the enhanced generation of OVA-specific B-cells in the cervical lymph nodes. Intranasal treatment with Hsp70-mB29a peptide-loaded PLGA nanoparticles suppressed proteoglycan-induced arthritis, leading to a significant reduction of disease. We have uncovered a role for PLGA nanoparticles to enhance CD4(+) T-cell mediated immunomodulation after nasal application. The exploitation of this differential regulation of nanoparticles to modulate nasal immune responses can lead to innovative vaccine development for prophylactic or therapeutic vaccination in infectious or autoimmune diseases. PMID- 22073185 TI - Estimating gene flow between refuges and crops: a case study of the biological control of Eriosoma lanigerum by Aphelinus mali in apple orchards. AB - Parasitoid disturbance populations in agroecosystems can be maintained through the provision of habitat refuges with host resources. However, specialized herbivores that feed on different host plants have been shown to form host specialized races. Parasitoids may subsequently specialize on these herbivore host races and therefore prefer parasitizing insects from the refuge, avoiding foraging on the crop. Evidence is therefore required that parasitoids are able to move between the refuge and the crop and that the refuge is a source of parasitoids, without being an important source of herbivore pests. A North-South transect trough the Chilean Central Valley was sampled, including apple orchards and surrounding Pyracantha coccinea (M. Roem) (Rosales: Rosacea) hedges that were host of Eriosoma lanigerum (Hemiptera: Aphididae), a globally important aphid pest of cultivated apples. At each orchard, aphid colonies were collected and taken back to the laboratory to sample the emerging hymenopteran parasitoid Aphelinus mali (Hymenoptera: Aphelinidae). Aphid and parasitoid individuals were genotyped using species-specific microsatellite loci and genetic variability was assessed. By studying genetic variation, natural geographic barriers of the aphid pest became evident and some evidence for incipient host-plant specialization was found. However, this had no effect on the population-genetic features of its most important parasitoid. In conclusion, the lack of genetic differentiation among the parasitoids suggests the existence of a single large and panmictic population, which could parasite aphids on apple orchards and on P. coccinea hedges. The latter could thus comprise a suitable and putative refuge for parasitoids, which could be used to increase the effectiveness of biological control. Moreover, the strong geographical differentiation of the aphid suggests local reinfestations occur mainly from other apple orchards with only low reinfestation from P. cocinnea hedges. Finally, we propose that the putative refuge could act as a source of parasitoids without being a major source of aphids. PMID- 22073186 TI - Archaeological soybean (Glycine max) in East Asia: does size matter? AB - The recently acquired archaeological record for soybean from Japan, China and Korea is shedding light on the context in which this important economic plant became associated with people and was domesticated. This paper examines archaeological (charred) soybean seed size variation to determine what insight can be gained from a comprehensive comparison of 949 specimens from 22 sites. Seed length alone appears to represent seed size change through time, although the length * width * thickness product has the potential to provide better size change resolution. A widespread early association of small seeded soybean is as old as 9000-8600 cal BP in northern China and 7000 cal BP in Japan. Direct AMS radiocarbon dates on charred soybean seeds indicate selection resulted in large seed sizes in Japan by 5000 cal BP (Middle Jomon) and in Korea by 3000 cal BP (Early Mumun). Soybean seeds recovered in China from the Shang through Han periods are similar in length to the large Korean and Japanese specimens, but the overall size of the large Middle and Late Jomon, Early Mumun through Three Kingdom seeds is significantly larger than any of the Chinese specimens. The archaeological record appears to disconfirm the hypothesis of a single domestication of soybean and supports the view informed by recent phyologenetic research that soybean was domesticated in several locations in East Asia. PMID- 22073187 TI - Context mediates antimicrobial efficacy of kinocidin congener peptide RP-1. AB - Structure-mechanism relationships are key determinants of host defense peptide efficacy. These relationships are influenced by anatomic, physiologic and microbiologic contexts. Structure-mechanism correlates were assessed for the synthetic peptide RP-1, modeled on microbicidal domains of platelet kinocidins. Antimicrobial efficacies and mechanisms of action against susceptible ((S)) or resistant ((R)) Salmonella typhimurium (ST), Staphylococcus aureus (SA), and Candida albicans (CA) strain pairs were studied at pH 7.5 and 5.5. Although RP-1 was active against all study organisms, it exhibited greater efficacy against bacteria at pH 7.5, but greater efficacy against CA at pH 5.5. RP-1 de-energized SA and CA, but caused hyperpolarization of ST in both pH conditions. However, RP 1 permeabilized ST(S) and CA strains at both pH, whereas permeabilization was modest for ST(R) or SA strain at either pH. Biochemical analysis, molecular modeling, and FTIR spectroscopy data revealed that RP-1 has indistinguishable net charge and backbone trajectories at pH 5.5 and 7.5. Yet, concordant with organism specific efficacy, surface plasmon resonance, and FTIR, molecular dynamics revealed modest helical order increases but greater RP-1 avidity and penetration of bacterial than eukaryotic lipid systems, particularly at pH 7.5. The present findings suggest that pH- and target-cell lipid contexts influence selective antimicrobial efficacy and mechanisms of RP-1 action. These findings offer new insights into selective antimicrobial efficacy and context-specificity of antimicrobial peptides in host defense, and support design strategies for potent anti-infective peptides with minimal concomitant cytotoxicity. PMID- 22073188 TI - RNA sequencing reveals differential expression of mitochondrial and oxidation reduction genes in the long-lived naked mole-rat when compared to mice. AB - The naked mole-rat (Heterocephalus glaber) is a long-lived, cancer resistant rodent and there is a great interest in identifying the adaptations responsible for these and other of its unique traits. We employed RNA sequencing to compare liver gene expression profiles between naked mole-rats and wild-derived mice. Our results indicate that genes associated with oxidoreduction and mitochondria were expressed at higher relative levels in naked mole-rats. The largest effect is nearly 300-fold higher expression of epithelial cell adhesion molecule (Epcam), a tumour-associated protein. Also of interest are the protease inhibitor, alpha2 macroglobulin (A2m), and the mitochondrial complex II subunit Sdhc, both ageing related genes found strongly over-expressed in the naked mole-rat. These results hint at possible candidates for specifying species differences in ageing and cancer, and in particular suggest complex alterations in mitochondrial and oxidation reduction pathways in the naked mole-rat. Our differential gene expression analysis obviated the need for a reference naked mole-rat genome by employing a combination of Illumina/Solexa and 454 platforms for transcriptome sequencing and assembling transcriptome contigs of the non-sequenced species. Overall, our work provides new research foci and methods for studying the naked mole-rat's fascinating characteristics. PMID- 22073189 TI - Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid lipofuscinosis. AB - We performed whole-exome sequencing in two autopsy-confirmed cases and an elderly unaffected control from a multigenerational family with autosomal dominant neuronal ceroid lipofuscinosis (ANCL). A novel single-nucleotide variation (c.344T>G) in the DNAJC5 gene was identified. Mutational screening in an independent family with autosomal dominant ANCL found an in-frame single codon deletion (c.346_348 delCTC) resulting in a deletion of p.Leu116del. These variants fulfill all genetic criteria for disease-causing mutations: they are found in unrelated families with the same disease, exhibit complete segregation between the mutation and the disease, and are absent in healthy controls. In addition, the associated amino acid substitutions are located in evolutionarily highly conserved residues and are predicted to functionally affect the encoded protein (CSPalpha). The mutations are located in a cysteine-string domain, which is required for membrane targeting/binding, palmitoylation, and oligomerization of CSPalpha. We performed a comprehensive in silico analysis of the functional and structural impact of both mutations on CSPalpha. We found that these mutations dramatically decrease the affinity of CSPalpha for the membrane. We did not identify any significant effect on palmitoylation status of CSPalpha. However, a reduction of CSPalpha membrane affinity may change its palmitoylation and affect proper intracellular sorting. We confirm that CSPalpha has a strong intrinsic aggregation propensity; however, it is not modified by the mutations. A complementary disease-network analysis suggests a potential interaction with other NCLs genes/pathways. This is the first replication study of the identification of DNAJC5 as the disease-causing gene for autosomal dominant ANCL. The identification of the novel gene in ANCL will allow us to gain a better understanding of the pathological mechanism of ANCLs and constitutes a great advance toward the development of new molecular diagnostic tests and may lead to the development of potential therapies. PMID- 22073190 TI - Brain biochemistry and personality: a magnetic resonance spectroscopy study. AB - To investigate the biochemical correlates of normal personality we utilized proton magnetic resonance spectroscopy ((1)H-MRS). Our sample consisted of 60 subjects ranging in age from 18 to 32 (27 females). Personality was assessed with the NEO Five-Factor Inventory (NEO-FFI). We measured brain biochemistry within the precuneus, the cingulate cortex, and underlying white matter. We hypothesized that brain biochemistry within these regions would predict individual differences across major domains of personality functioning. Biochemical models were fit for all personality domains including Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness. Our findings involved differing concentrations of Choline (Cho), Creatine (Cre), and N-acetylaspartate (NAA) in regions both within (i.e., posterior cingulate cortex) and white matter underlying (i.e., precuneus) the Default Mode Network (DMN). These results add to an emerging literature regarding personality neuroscience, and implicate biochemical integrity within the default mode network as constraining major personality domains within normal human subjects. PMID- 22073191 TI - NNAlign: a web-based prediction method allowing non-expert end-user discovery of sequence motifs in quantitative peptide data. AB - Recent advances in high-throughput technologies have made it possible to generate both gene and protein sequence data at an unprecedented rate and scale thereby enabling entirely new "omics"-based approaches towards the analysis of complex biological processes. However, the amount and complexity of data that even a single experiment can produce seriously challenges researchers with limited bioinformatics expertise, who need to handle, analyze and interpret the data before it can be understood in a biological context. Thus, there is an unmet need for tools allowing non-bioinformatics users to interpret large data sets. We have recently developed a method, NNAlign, which is generally applicable to any biological problem where quantitative peptide data is available. This method efficiently identifies underlying sequence patterns by simultaneously aligning peptide sequences and identifying motifs associated with quantitative readouts. Here, we provide a web-based implementation of NNAlign allowing non-expert end users to submit their data (optionally adjusting method parameters), and in return receive a trained method (including a visual representation of the identified motif) that subsequently can be used as prediction method and applied to unknown proteins/peptides. We have successfully applied this method to several different data sets including peptide microarray-derived sets containing more than 100,000 data points. NNAlign is available online at http://www.cbs.dtu.dk/services/NNAlign. PMID- 22073192 TI - Objective measures of emotion related to brand attitude: a new way to quantify emotion-related aspects relevant to marketing. AB - With this study we wanted to test the hypothesis that individual like and dislike as occurring in relation to brand attitude can be objectively assessed. First, individuals rated common brands with respect to subjective preference. Then, they volunteered in an experiment during which their most liked and disliked brand names were visually presented while three different objective measures were taken. Participant's eye blinks as responses to acoustic startle probes were registered with electromyography (EMG) (i) and their skin conductance (ii) and their heart rate (iii) were recorded. We found significantly reduced eye blink amplitudes related to liked brand names compared to disliked brand names. This finding suggests that visual perception of liked brand names elicits higher degrees of pleasantness, more positive emotion and approach-oriented motivation than visual perception of disliked brand names. Also, skin conductance and heart rate were both reduced in case of liked versus disliked brand names. We conclude that all our physiological measures highlight emotion-related differences depending on the like and dislike toward individual brands. We suggest that objective measures should be used more frequently to quantify emotion-related aspects of brand attitude. In particular, there might be potential interest to introduce startle reflex modulation to measure emotion-related impact during product development, product design and various further fields relevant to marketing. Our findings are discussed in relation to the idea that self reported measures are most often cognitively polluted. PMID- 22073193 TI - Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting. AB - BACKGROUND: The Surviving Sepsis Campaign (SSC) guidelines for the management of severe sepsis (SS) and septic shock (SSh) have been recommended to reduce morbidity and mortality. MATERIALS AND METHODS: A quasi-experimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize SS and SSh shock patients' clinical outcomes were performed by applying sepsis bundles (6- and 24-hour) in May 2006. We compared bundle compliance and patient outcomes before (July 2005-April 2006) and after (May 2006-December 2009) implementation of the interventions. RESULTS: A total of 564 SS and SSh patients were identified. Prior to the intervention, compliance with the 6 hour-sepsis resuscitation bundle was only 6%. After the intervention, compliance was as follows: 8.2% from May to December 2006, 9.3% in 2007, 21.1% in 2008 and 13.7% in 2009. For the 24 hour-management bundle, baseline compliance was 15.0%. After the intervention, compliance was 15.1% from May to December 2006, 21.4% in 2007, 27.8% in 2008 and 44.4% in 2009. The in-hospital mortality was 54.0% from July 2005 to April 2006, 41.1% from May to December 2006, 39.3% in 2007, 41.4% in 2008 and 16.2% in 2009. CONCLUSION: These results suggest reducing SS and SSh patient mortality is a complex process that involves multiple performance measures and interventions. PMID- 22073194 TI - Divalent cations and redox conditions regulate the molecular structure and function of visinin-like protein-1. AB - The NCS protein Visinin-like Protein 1 (VILIP-1) transduces calcium signals in the brain and serves as an effector of the non-retinal receptor guanylyl cyclases (GCs) GC-A and GC-B, and nicotinic acetyl choline receptors (nAchR). Analysis of the quaternary structure of VILIP-1 in solution reveals the existence of monomeric and dimeric species, the relative contents of which are affected but not exclusively regulated by divalent metal ions and Redox conditions. Using small-angle X-ray scattering, we have investigated the low resolution structure of the calcium-bound VILIP-1 dimer under reducing conditions. Scattering profiles for samples with high monomeric and dimeric contents have been obtained. The dimerization interface involves residues from EF-hand regions EF3 and EF4.Using monolayer adsorption experiments, we show that myristoylated and unmyristoylated VILIP-1 can bind lipid membranes. The presence of calcium only marginally improves binding of the protein to the monolayer, suggesting that charged residues at the protein surface may play a role in the binding process.In the presence of calcium, VILIP-1 undergoes a conformational re-arrangement, exposing previously hidden surfaces for interaction with protein partners. We hypothesise a working model where dimeric VILIP-1 interacts with the membrane where it binds membrane-bound receptors in a calcium-dependent manner. PMID- 22073195 TI - Killing them with kindness? In-hive medications may inhibit xenobiotic efflux transporters and endanger honey bees. AB - BACKGROUND: Honey bees (Apis mellifera) have recently experienced higher than normal overwintering colony losses. Many factors have been evoked to explain the losses, among which are the presence of residues of pesticides and veterinary products in hives. Multiple residues are present at the same time, though most often in low concentrations so that no single product has yet been associated with losses. Involvement of a combination of residues to losses may however not be excluded. To understand the impact of an exposure to combined residues on honey bees, we propose a mechanism-based strategy, focusing here on Multi-Drug Resistance (MDR) transporters as mediators of those interactions. METHODOLOGY/PRINCIPAL FINDINGS: Using whole-animal bioassays, we demonstrate through inhibition by verapamil that the widely used organophosphate and pyrethroid acaricides coumaphos and tau-fluvalinate, and three neonicotinoid insecticides: imidacloprid, acetamiprid and thiacloprid are substrates of one or more MDR transporters. Among the candidate inhibitors of honey bee MDR transporters is the in-hive antibiotic oxytetracycline. Bees prefed oxytetracycline were significantly sensitized to the acaricides coumaphos and tau fluvalinate, suggesting that the antibiotic may interfere with the normal excretion or metabolism of these pesticides. CONCLUSIONS/SIGNIFICANCE: Many bee hives receive regular treatments of oxytetracycline and acaricides for prevention and treatment of disease and parasites. Our results suggest that seasonal co application of these medicines to bee hives could increase the adverse effects of these and perhaps other pesticides. Our results also demonstrate the utility of a mechanism-based strategy. By identifying pesticides and apicultural medicines that are substrates and inhibitors of xenobiotic transporters we prioritize the testing of those chemical combinations most likely to result in adverse interactions. PMID- 22073196 TI - Methylation of the CpG sites only on the sense strand of the APC gene is specific for hepatocellular carcinoma. AB - Hypermethylation of the promoter of the tumor suppressor gene, adenomatous polyposis coli (APC), occurs in various malignancies, including hepatocellular carcinoma (HCC). However, reports on the specificity of the methylation of the APC gene for HCC have varied. To gain insight into how these variations occur, bisulfite PCR sequencing was performed to analyze the methylation status of both sense and antisense strands of the APC gene in samples of HCC tissue, matched adjacent non-HCC liver tissue, hepatitis, cirrhosis, and normal liver tissues. DNA derived from fetal liver and 12 nonhepatic normal tissue was also examined. These experiments revealed liver-specific, antisense strand-biased CpG methylation of the APC gene and suggested that, although methylation of the antisense strand of the APC gene exists in normal liver and other non-HCC disease liver tissue, methylation of the sense strand of the APC gene occurs predominantly in HCC. To determine the effect of the DNA strand on the specificity of the methylated APC gene as a biomarker for HCC detection, quantitative methylation-specific PCR assays for sense and antisense strand DNA were developed and performed on DNA isolated from HCC (n = 58), matched adjacent non-HCC (n = 58), cirrhosis (n = 41), and hepatitis (n = 39). Receiver operating characteristic curves were constructed. With the cutoff value set at the limit of detection, the specificity of sense and antisense strand methylation was 84% and 43%, respectively, and sensitivity was 67.2% and 72.4%, respectively. This result demonstrated that the identity of the methylated DNA strand impacted the specificity of APC for HCC detection. Interestingly, methylation of the sense strand of APC occurred in 40% of HCCs from patients with serum AFP levels less than 20 ng/mL, suggesting a potential role for APC as a biomarker to complement AFP in HCC screening. PMID- 22073197 TI - Phylogenetic diversity, host-specificity and community profiling of sponge associated bacteria in the northern Gulf of Mexico. AB - BACKGROUND: Marine sponges can associate with abundant and diverse consortia of microbial symbionts. However, associated bacteria remain unexamined for the majority of host sponges and few studies use phylogenetic metrics to quantify symbiont community diversity. DNA fingerprinting techniques, such as terminal restriction fragment length polymorphisms (T-RFLP), might provide rapid profiling of these communities, but have not been explicitly compared to traditional methods. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the bacterial communities associated with the marine sponges Hymeniacidon heliophila and Haliclona tubifera, a sympatric tunicate, Didemnum sp., and ambient seawater from the northern Gulf of Mexico by combining replicated clone libraries with T-RFLP analyses of 16S rRNA gene sequences. Clone libraries revealed that bacterial communities associated with the two sponges exhibited lower species richness and lower species diversity than seawater and tunicate assemblages, with differences in species composition among all four source groups. T-RFLP profiles clustered microbial communities by source; individual T-RFs were matched to the majority (80.6%) of clone library sequences, indicating that T-RFLP analysis can be used to rapidly profile these communities. Phylogenetic metrics of community diversity indicated that the two sponge-associated bacterial communities include dominant and host-specific bacterial lineages that are distinct from bacteria recovered from seawater, tunicates, and unrelated sponge hosts. In addition, a large proportion of the symbionts associated with H. heliophila were shared with distant, conspecific host populations in the southwestern Atlantic (Brazil). CONCLUSIONS/SIGNIFICANCE: The low diversity and species-specific nature of bacterial communities associated with H. heliophila and H. tubifera represent a distinctly different pattern from other, reportedly universal, sponge-associated bacterial communities. Our replicated sampling strategy, which included samples that reflect the ambient environment, allowed us to differentiate resident symbionts from potentially transient or prey bacteria. Pairing replicated clone library construction with rapid community profiling via T-RFLP analyses will greatly facilitate future studies of sponge-microbe symbioses. PMID- 22073198 TI - Optimized mouse model for the imaging of tumor metastasis upon experimental therapy. AB - Development of new cancer treatments focuses increasingly on the relation of cancer tissue with its microenvironment. A major obstacle for the development of new anti-cancer therapies has been the lack of relevant animal models that would reproduce all the events involved in disease progression from the early-stage primary tumor until the development of mature metastatic tissue. To this end, we have developed a readily imageable mouse model of colorectal cancer featuring highly reproducible formation of spontaneous liver metastases derived from intrasplenic primary tumors. We optimized several experimental variables, and found that the correct choice of cell line and the genetic background, as well as the age of the recipient mice, were critical for establishing a useful model system. Among a panel of colorectal cancer cell lines tested, the epithelial carcinoma HT29 line was found to be the most suitable in terms of producing homogeneous tumor growth and metastases. In our hands, SCID mice at the age of 125 days or older were the most suitable in supporting consistent HT29 tumor growth after splenic implantation followed by reproducible metastasis to the liver. A magnetic resonance imaging (MRI) protocol was optimized for use with this mouse model, and demonstrated to be a powerful method for analyzing the antitumor effects of an experimental therapy. Specifically, we used this system to with success to verify by MRI monitoring the efficacy of an intrasplenically administered oncolytic adenovirus therapy in reducing visceral tumor load and development of liver metastases. In summary, we have developed a highly optimized mouse model for liver metastasis of colorectal cancer, which allows detection of the tumor load at the whole body level and enables an accurate timing of therapeutic interventions to target different stages of cancer progression and metastatic development. PMID- 22073199 TI - Na+/K+-ATPase is present in scrapie-associated fibrils, modulates PrP misfolding in vitro and links PrP function and dysfunction. AB - Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C), to the disease-associated form, PrP(Sc), through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C) and PrP(Sc) isoforms. A wealth of evidence implicates other non-PrP molecules as active participants in the misfolding process, to catalyse and direct the conformational conversion of PrP(C) or to provide a scaffold ensuring correct alignment of PrP(C) and PrP(Sc) during conversion. Such molecules may be specific to different scrapie strains to facilitate differential prion protein misfolding. Since molecular cofactors may become integrated into the growing protein fibril during prion conversion, we have investigated the proteins contained in prion disease-specific deposits by shotgun proteomics of scrapie-associated fibrils (SAF) from mice infected with 3 different strains of mouse-passaged scrapie. Concomitant use of negative control preparations allowed us to identify and discount proteins that are enriched non-specifically by the SAF isolation protocol. We found several proteins that co-purified specifically with SAF from infected brains but none of these were reproducibly and demonstrably specific for particular scrapie strains. The alpha-chain of Na(+)/K(+)-ATPase was common to SAF from all 3 strains and we tested the ability of this protein to modulate in vitro misfolding of recombinant PrP. Na(+)/K(+)-ATPase enhanced the efficiency of disease-specific conversion of recombinant PrP suggesting that it may act as a molecular cofactor. Consistent with previous results, the same protein inhibited fibrillisation kinetics of recombinant PrP. Since functional interactions between PrP(C) and Na(+)/K(+)-ATPase have previously been reported in astrocytes, our data highlight this molecule as a key link between PrP function, dysfunction and misfolding. PMID- 22073200 TI - Genome-wide scan identifies loci associated with classical BSE occurrence. AB - Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Sequence variations in the coding region of the prion gene (PRNP) have been associated with acquired transmissible spongiform encephalopathy (TSE) susceptibility in mammals; however, this is not the case in cattle. It has been hypothesized that genes, in addition to the prion gene, contribute to genetic susceptibility of acquired TSEs. Accordingly, genetic studies of classical BSE in cattle identified loci other than PRNP that are associated with disease incidence. The objective of this study was to utilize a genome-wide association study to test for genetic loci associated with classical BSE. The samples include 143 BSE affected (case) and 173 unaffected half sib (control) animals collected in the mid 1990s in Southern England. The data analysis identifies loci on two different chromosomes associated with BSE disease occurrence. Most notable is a single nucleotide polymorphism on chromosome 1 at 29.15 Mb that is associated with BSE disease (p = 3.09E-05). Additionally, a locus on chromosome 14, within a cluster of SNPs showed a trend toward significance (p = 5.24E-05). It is worth noting that in a human vCJD study markers on human chromosome 8, a region with shared synteny to the region identified on cattle chromosome 14, were associated with disease. Further, our candidate genes appear to have plausible biological relevance with the known etiology of TSE disease. One of the candidate genes is hypothetical gene LOC521010, similar to FK506 binding protein 2 located on chromosome 1 at 29.32 Mb. This gene encodes a protein that is a member of the immunophilin protein family and is involved in basic cellular processes including protein folding. The chromosomal regions identified in this study and candidate genes within these regions merit further investigation. PMID- 22073201 TI - Neurons controlling voluntary vocalization in the macaque ventral premotor cortex. AB - The voluntary control of phonation is a crucial achievement in the evolution of speech. In humans, ventral premotor cortex (PMv) and Broca's area are known to be involved in voluntary phonation. In contrast, no neurophysiological data are available about the role of the oro-facial sector of nonhuman primates PMv in this function. In order to address this issue, we recorded PMv neurons from two monkeys trained to emit coo-calls. Results showed that a population of motor neurons specifically fire during vocalization. About two thirds of them discharged before sound onset, while the remaining were time-locked with it. The response of vocalization-selective neurons was present only during conditioned (voluntary) but not spontaneous (emotional) sound emission. These data suggest that the control of vocal production exerted by PMv neurons constitutes a newly emerging property in the monkey lineage, shedding light on the evolution of phonation-based communication from a nonhuman primate species. PMID- 22073202 TI - Spontaneous development of full weight-supported stepping after complete spinal cord transection in the neonatal opossum, Monodelphis domestica. AB - Spinal cord trauma in the adult nervous system usually results in permanent loss of function below the injury level. The immature spinal cord has greater capacity for repair and can develop considerable functionality by adulthood. This study used the marsupial laboratory opossum Monodelphis domestica, which is born at a very early stage of neural development. Complete spinal cord transection was made in the lower-thoracic region of pups at postnatal-day 7 (P7) or P28, and the animals grew to adulthood. Injury at P7 resulted in a dense neuronal tissue bridge that connected the two ends of the cord; retrograde neuronal labelling indicated that supraspinal and propriospinal innervation spanned the injury site. This repair was associated with pronounced behavioural recovery, coordinated gait and an ability to use hindlimbs when swimming. Injury at P28 resulted in a cyst like cavity encased in scar tissue forming at the injury site. Using retrograde labelling, no labelled brainstem or propriospinal neurons were found above the lesion, indicating that detectable neuronal connectivity had not spanned the injury site. However, these animals could use their hindlimbs to take weight supporting steps but could not use their hindlimbs when swimming. White matter, demonstrated by Luxol Fast Blue staining, was present in the injury site of P7- but not P28-injured animals. Overall, these studies demonstrated that provided spinal injury occurs early in development, regrowth of supraspinal innervation is possible. This repair appears to lead to improved functional outcomes. At older ages, even without detectable axonal growth spanning the injury site, substantial development of locomotion was still possible. This outcome is discussed in conjunction with preliminary findings of differences in the local propriospinal circuits following spinal cord injury (demonstrated with fluororuby labelling), which may underlie the weight bearing locomotion observed in the apparent absence of axons bridging the lesion site in P28-injured Monodelphis. PMID- 22073203 TI - Willingness to share research data is related to the strength of the evidence and the quality of reporting of statistical results. AB - BACKGROUND: The widespread reluctance to share published research data is often hypothesized to be due to the authors' fear that reanalysis may expose errors in their work or may produce conclusions that contradict their own. However, these hypotheses have not previously been studied systematically. METHODS AND FINDINGS: We related the reluctance to share research data for reanalysis to 1148 statistically significant results reported in 49 papers published in two major psychology journals. We found the reluctance to share data to be associated with weaker evidence (against the null hypothesis of no effect) and a higher prevalence of apparent errors in the reporting of statistical results. The unwillingness to share data was particularly clear when reporting errors had a bearing on statistical significance. CONCLUSIONS: Our findings on the basis of psychological papers suggest that statistical results are particularly hard to verify when reanalysis is more likely to lead to contrasting conclusions. This highlights the importance of establishing mandatory data archiving policies. PMID- 22073204 TI - Identification of controlled-complexity thermal therapy models derived from magnetic resonance thermometry images. AB - Medical imaging provides information valuable in diagnosis, planning, and control of therapies. In this paper, we develop a method that uses a specific type of imaging--the magnetic resonance thermometry--to identify accurate and computationally efficient site and patient-specific computer models for thermal therapies, such as focused ultrasound surgery, hyperthermia, and thermally triggered targeted drug delivery. The developed method uses a sequence of acquired MR thermometry images to identify a treatment model describing the deposition and dissipation of thermal energy in tissues. The proper orthogonal decomposition of thermal images is first used to identify a set of empirical eigenfunctions, which captures spatial correlations in the thermal response of tissues. Using the reduced subset of eigenfunction as a functional basis, low dimensional thermal response and the ultrasound specific absorption rate models are then identified. Once identified, the treatment models can be used to plan, optimize, and control the treatment. The developed approach is validated experimentally using the results of MR thermal imaging of a tissue phantom during focused ultrasound sonication. The validation demonstrates that our approach produces accurate low-dimensional treatment models and provides a convenient tool for balancing the accuracy of model predictions and the computational complexity of the treatment models. PMID- 22073205 TI - Laser-based single-axon transection for high-content axon injury and regeneration studies. AB - The investigation of the regenerative response of the neurons to axonal injury is essential to the development of new axoprotective therapies. Here we study the retinal neuronal RGC-5 cell line after laser transection, demonstrating that the ability of these cells to initiate a regenerative response correlates with axon length and cell motility after injury. We show that low energy picosecond laser pulses can achieve transection of unlabeled single axons in vitro and precisely induce damage with micron precision. We established the conditions to achieve axon transection, and characterized RGC-5 axon regeneration and cell body response using time-lapse microscopy. We developed an algorithm to analyze cell trajectories and established correlations between cell motility after injury, axon length, and the initiation of the regeneration response. The characterization of the motile response of axotomized RGC-5 cells showed that cells that were capable of repair or regrowth of damaged axons migrated more slowly than cells that could not. Moreover, we established that RGC-5 cells with long axons could not recover their injured axons, and such cells were much more motile. The platform we describe allows highly controlled axonal damage with subcellular resolution and the performance of high-content screening in cell cultures. PMID- 22073206 TI - Determinants of the differential antizyme-binding affinity of ornithine decarboxylase. AB - Ornithine decarboxylase (ODC) is a ubiquitous enzyme that is conserved in all species from bacteria to humans. Mammalian ODC is degraded by the proteasome in a ubiquitin-independent manner by direct binding to the antizyme (AZ). In contrast, Trypanosoma brucei ODC has a low binding affinity toward AZ. In this study, we identified key amino acid residues that govern the differential AZ binding affinity of human and Trypanosoma brucei ODC. Multiple sequence alignments of the ODC putative AZ-binding site highlights several key amino acid residues that are different between the human and Trypanosoma brucei ODC protein sequences, including residue 119, 124,125, 129, 136, 137 and 140 (the numbers is for human ODC). We generated a septuple human ODC mutant protein where these seven bases were mutated to match the Trypanosoma brucei ODC protein sequence. The septuple mutant protein was much less sensitive to AZ inhibition compared to the WT protein, suggesting that these amino acid residues play a role in human ODC-AZ binding. Additional experiments with sextuple mutants suggest that residue 137 plays a direct role in AZ binding, and residues 119 and 140 play secondary roles in AZ binding. The dissociation constants were also calculated to quantify the affinity of the ODC-AZ binding interaction. The K(d) value for the wild type ODC protein-AZ heterodimer ([ODC_WT]-AZ) is approximately 0.22 MUM, while the K(d) value for the septuple mutant-AZ heterodimer ([ODC_7M]-AZ) is approximately 12.4 MUM. The greater than 50-fold increase in [ODC_7M]-AZ binding affinity shows that the ODC-7M enzyme has a much lower binding affinity toward AZ. For the mutant proteins ODC_7M(-Q119H) and ODC_7M(-V137D), the K(d) was 1.4 and 1.2 MUM, respectively. These affinities are 6-fold higher than the WT_ODC K(d), which suggests that residues 119 and 137 play a role in AZ binding. PMID- 22073208 TI - Infant and child mortality in India in the last two decades: a geospatial analysis. AB - BACKGROUND: Studies examining the intricate interplay between poverty, female literacy, child malnutrition, and child mortality are rare in demographic literature. Given the recent focus on Millennium Development Goals 4 (child survival) and 5 (maternal health), we explored whether the geographic regions that were underprivileged in terms of wealth, female literacy, child nutrition, or safe delivery were also grappling with the elevated risk of child mortality; whether there were any spatial outliers; whether these relationships have undergone any significant change over historical time periods. METHODOLOGY: The present paper attempted to investigate these critical questions using data from household surveys like NFHS 1992-1993, NFHS 1998-1999 and DLHS 2002-2004. For the first time, we employed geo-spatial techniques like Moran's-I, univariate LISA, bivariate LISA, spatial error regression, and spatiotemporal regression to address the research problem. For carrying out the geospatial analysis, we classified India into 76 natural regions based on the agro-climatic scheme proposed by Bhat and Zavier (1999) following the Census of India Study and all estimates were generated for each of the geographic regions. RESULT/CONCLUSIONS: This study brings out the stark intra-state and inter-regional disparities in infant and under-five mortality in India over the past two decades. It further reveals, for the first time, that geographic regions that were underprivileged in child nutrition or wealth or female literacy were also likely to be disadvantaged in terms of infant and child survival irrespective of the state to which they belong. While the role of economic status in explaining child malnutrition and child survival has weakened, the effect of mother's education has actually become stronger over time. PMID- 22073207 TI - Carbon dynamics, development and stress responses in Arabidopsis: involvement of the APL4 subunit of ADP-glucose pyrophosphorylase (starch synthesis). AB - An Arabidopsis thaliana T-DNA insertional mutant was identified and characterized for enhanced tolerance to the singlet-oxygen-generating herbicide atrazine in comparison to wild-type. This enhanced atrazine tolerance mutant was shown to be affected in the promoter structure and in the regulation of expression of the APL4 isoform of ADP-glucose pyrophosphorylase, a key enzyme of the starch biosynthesis pathway, thus resulting in decrease of APL4 mRNA levels. The impact of this regulatory mutation was confirmed by the analysis of an independent T-DNA insertional mutant also affected in the promoter of the APL4 gene. The resulting tissue-specific modifications of carbon partitioning in plantlets and the effects on plantlet growth and stress tolerance point out to specific and non-redundant roles of APL4 in root carbon dynamics, shoot-root relationships and sink regulations of photosynthesis. Given the effects of exogenous sugar treatments and of endogenous sugar levels on atrazine tolerance in wild-type Arabidopsis plantlets, atrazine tolerance of this apl4 mutant is discussed in terms of perception of carbon status and of investment of sugar allocation in xenobiotic and oxidative stress responses. PMID- 22073209 TI - FMRI supports the sensorimotor theory of motor resonance. AB - The neural mechanisms mediating the activation of the motor system during action observation, also known as motor resonance, are of major interest to the field of motor control. It has been proposed that motor resonance develops in infants through Hebbian plasticity of pathways connecting sensory and motor regions that fire simultaneously during imitation or self movement observation. A fundamental problem when testing this theory in adults is that most experimental paradigms involve actions that have been overpracticed throughout life. Here, we directly tested the sensorimotor theory of motor resonance by creating new visuomotor representations using abstract stimuli (motor symbols) and identifying the neural networks recruited through fMRI. We predicted that the network recruited during action observation and execution would overlap with that recruited during observation of new motor symbols. Our results indicate that a network consisting of premotor and posterior parietal cortex, the supplementary motor area, the inferior frontal gyrus and cerebellum was activated both by new motor symbols and by direct observation of the corresponding action. This tight spatial overlap underscores the importance of sensorimotor learning for motor resonance and further indicates that the physical characteristics of the perceived stimulus are irrelevant to the evoked response in the observer. PMID- 22073210 TI - Age-corrected beta cell mass following onset of type 1 diabetes mellitus correlates with plasma C-peptide in humans. AB - BACKGROUND: The inability to produce insulin endogenously precipitates the clinical symptoms of type 1 diabetes mellitus. However, the dynamic trajectory of beta cell destruction following onset remains unclear. Using model-based inference, the severity of beta cell destruction at onset decreases with age where, on average, a 40% reduction in beta cell mass was sufficient to precipitate clinical symptoms at 20 years of age. While plasma C-peptide provides a surrogate measure of endogenous insulin production post-onset, it is unclear as to whether plasma C-peptide represents changes in beta cell mass or beta cell function. The objective of this paper was to determine the relationship between beta cell mass and endogenous insulin production post-onset. METHODS AND FINDINGS: Model-based inference was used to compare direct measures of beta cell mass in 102 patients against contemporary measures of plasma C-peptide obtained from three studies that collectively followed 834 patients post-onset of clinical symptoms. An empirical Bayesian approach was used to establish the level of confidence associated with the model prediction. Age-corrected estimates of beta cell mass that were inferred from a series of landmark pancreatic autopsy studies significantly correlate (p>0.9995) with contemporary measures of plasma C-peptide levels following onset. CONCLUSIONS: Given the correlation between beta cell mass and plasma C-peptide following onset, plasma C-peptide may provide a surrogate measure of beta cell mass in humans. The clinical relevance of this study is that therapeutic strategies that provide an increase in plasma C-peptide over the predicted value for an individual may actually improve beta cell mass. The model predictions may establish a standard historical "control" group - a prior in a Bayesian context - for clinical trials. PMID- 22073211 TI - High genetic diversity despite the potential for stepping-stone colonizations in an invasive species of gecko on Moorea, French Polynesia. AB - Invasive species often have reduced genetic diversity, but the opposite can be true if there have been multiple introductions and genetic admixture. Reduced diversity is most likely soon after establishment, in remote locations, when there is lower propagule pressure and with stepping-stone colonizations. The common house gecko (Hemidactylus frenatus) was introduced to Moorea, French Polynesia in the remote eastern Pacific within the last two decades and accordingly is expected to exhibit low diversity. In contrast, we show that H. frenatus on Moorea has exceptionally high genetic diversity, similar to that near the native range in Asia and much higher than reported for other Pacific island reptiles. The high diversity in this recently founded population likely reflects extensive genetic admixture in source population(s) and a life history that promotes retention of diversity. These observations point to the importance of understanding range-wide dynamics of genetic admixture in highly invasive species. PMID- 22073212 TI - Expression screening of fusion partners from an E. coli genome for soluble expression of recombinant proteins in a cell-free protein synthesis system. AB - While access to soluble recombinant proteins is essential for a number of proteome studies, preparation of purified functional proteins is often limited by the protein solubility. In this study, potent solubility-enhancing fusion partners were screened from the repertoire of endogenous E. coli proteins. Based on the presumed correlation between the intracellular abundance and folding efficiency of proteins, PCR-amplified ORFs of a series of highly abundant E. coli proteins were fused with aggregation-prone heterologous proteins and then directly expressed for quantitative estimation of the expression efficiency of soluble translation products. Through two-step screening procedures involving the expression of 552 fusion constructs targeted against a series of cytokine proteins, we were able to discover a number of endogenous E. coli proteins that dramatically enhanced the soluble expression of the target proteins. This strategy of cell-free expression screening can be extended to quantitative, global analysis of genomic resources for various purposes. PMID- 22073213 TI - Cervical remodeling/ripening at term and preterm delivery: the same mechanism initiated by different mediators and different effector cells. AB - BACKGROUND: Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We previously demonstrated that complement activation plays a causative role in cervical remodeling that leads to PTD in mice. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that complement activation is not required for the physiological process that leads to term delivery in mice. Neither increased C3 cervical deposition nor increased C3a and C5a serum levels were observed at term. In addition, macrophages infiltration was found in PTD in contrast to term delivery were no leukocytes were found. Despite the different role of complement and different cellular effector cells, PTD and term delivery share a common dowsntream pathway characterized by increased metalloproteinases (MMPs) release and increased collagen degradation. However, different sources of MMPs were identified. Macrophages are the source of MMPs in PTD while cervical fibroblasts and columnar epithelial cells synthesize MMPs at term delivery. A dramatic diminution in serum progesterone levels precedes parturition at term but not in PTD, suggesting that progesterone withdrawal initiates cervical remodeling at term. On the other hand, MMPs release in PTD is triggered by C5a. CONCLUSION AND SIGNIFICANCE: In conclusion, preterm and term cervical remodeling occur through the same mechanism but they are initiated by different mediators and effector cells. That complement activation is required for PTD but not for the physiological process that leads to term delivery, suggests that complement is a potential specific biomarker and selective target to prevent PTD and thus avert neonatal mortality and morbidity. PMID- 22073214 TI - Asymmetric cell division and Notch signaling specify dopaminergic neurons in Drosophila. AB - In Drosophila, dopaminergic (DA) neurons can be found from mid embryonic stages of development till adulthood. Despite their functional involvement in learning and memory, not much is known about the developmental as well as molecular mechanisms involved in the events of DA neuronal specification, differentiation and maturation. In this report we demonstrate that most larval DA neurons are generated during embryonic development. Furthermore, we show that loss of function (l-o-f) mutations of genes of the apical complex proteins in the asymmetric cell division (ACD) machinery, such as inscuteable and bazooka result in supernumerary DA neurons, whereas l-o-f mutations of genes of the basal complex proteins such as numb result in loss or reduction of DA neurons. In addition, when Notch signaling is reduced or abolished, additional DA neurons are formed and conversely, when Notch signaling is activated, less DA neurons are generated. Our data demonstrate that both ACD and Notch signaling are crucial mechanisms for DA neuronal specification. We propose a model in which ACD results in differential Notch activation in direct siblings and in this context Notch acts as a repressor for DA neuronal specification in the sibling that receives active Notch signaling. Our study provides the first link of ACD and Notch signaling in the specification of a neurotransmitter phenotype in Drosophila. Given the high degree of conservation between Drosophila and vertebrate systems, this study could be of significance to mechanisms of DA neuronal differentiation not limited to flies. PMID- 22073215 TI - Genome-wide binding map of the HIV-1 Tat protein to the human genome. AB - The HIV-1 Trans-Activator of Transcription (Tat) protein binds to multiple host cellular factors and greatly enhances the level of transcription of the HIV genome. While Tat's control of viral transcription is well-studied, much less is known about the interaction of Tat with the human genome. Here, we report the genome-wide binding map of Tat to the human genome in Jurkat T cells using chromatin immunoprecipitation combined with next-generation sequencing. Surprisingly, we found that ~53% of the Tat target regions are within DNA repeat elements, greater than half of which are Alu sequences. The remaining target regions are located in introns and distal intergenic regions; only ~7% of Tat bound regions are near transcription start sites (TSS) at gene promoters. Interestingly, Tat binds to promoters of genes that, in Jurkat cells, are bound by the ETS1 transcription factor, the CBP histone acetyltransferase and/or are enriched for histone H3 lysine 4 tri-methylation (H3K4me3) and H3K27me3. Tat binding is associated with genes enriched with functions in T cell biology and immune response. Our data reveal that Tat's interaction with the host genome is more extensive than previously thought, with potentially important implications for the viral life cycle. PMID- 22073216 TI - Perceptions of conflict of interest disclosures among peer reviewers. AB - BACKGROUND: Disclosure of financial conflicts of interest (COI) is intended to help reviewers assess the impact of potential bias on the validity of research results; however, there have been no empiric assessments of how reviewers understand and use disclosures in article evaluation. We investigate reviewers' perceptions of potential bias introduced by particular author disclosures, and whether reviewer characteristics are associated with a greater likelihood of perceiving bias. METHODOLOGY/PRINCIPAL FINDINGS: Of the 911 active reviewers from the Annals of Emergency Medicine, 410 were randomly selected and invited to complete our web-based, 3-part survey. We completed descriptive analysis of all survey responses and compared those responses across reviewer characteristics using 2 * 2 analyses and the Fisher exact test. We had a response rate of 54%. The majority of reviewers surveyed reported a high level of skepticism regarding financial relationships between authors and industry without a clear or consistent translation of that skepticism into the self-reported actions that characterize manuscript assessment. Only 13% of respondents believed physician consultants authoring articles based on company data are likely to have unlimited data access. 54% believed that bias most likely exists with any honorarium, regardless of monetary amount. Between 46% and 64%, depending on the type of financial relationship disclosed, reported that their recommendation for publication remains unchanged. Respondents reporting personal financial ties to industry were less likely to perceive bias in industry relationships and less likely to believe that bias exists with any monetary amount of honoraria. CONCLUSIONS: We recommend that the monetary amount of all financial relationships be reported with manuscript submissions, lead authors certify that they have unrestricted access to data, and reviewers disclose any financial ties to industry whether or not they are related to the manuscript under review. Further research is required to better understand reviewers' perceptions of financial relationships between authors and industry in order to develop clear and consistent guidelines for incorporating the perception of potential bias into manuscript assessments. PMID- 22073217 TI - A quorum-sensing factor in vegetative Dictyostelium discoideum cells revealed by quantitative migration analysis. AB - BACKGROUND: Many cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS). In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase. METHODS AND FINDINGS: To investigate the role of cell density on cell migration in the growth phase, we use multisite timelapse microscopy and automated cell tracking. This analysis reveals a high heterogeneity within a given cell population, and the necessity to use large data sets to draw reliable conclusions on cell motion. In average, motion is persistent for short periods of time (t <= 5 min), but normal diffusive behavior is recovered over longer time periods. The persistence times are positively correlated with the migrated distances. Interestingly, the migrated distance decreases as well with cell density. The adaptation of cell migration to cell density highlights the role of a secreted quorum sensing factor (QSF) on cell migration. Using a simple model describing the balance between the rate of QSF generation and the rate of QSF dilution, we were able to gather all experimental results into a single master curve, showing a sharp cell transition between high and low motile behaviors with increasing QSF. CONCLUSION: This study unambiguously demonstrates the central role played by QSF on amoeboid motion in the growth phase. PMID- 22073218 TI - GLUT 5 is not over-expressed in breast cancer cells and patient breast cancer tissues. AB - F18 2-Fluoro 2-deoxyglucose (FDG) has been the gold standard in positron emission tomography (PET) oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues. PMID- 22073219 TI - Moderate antiproteinuric effect of add-on aldosterone blockade with eplerenone in non-diabetic chronic kidney disease. A randomized cross-over study. AB - BACKGROUND: Reduction of proteinuria and blood pressure (BP) with blockers of the renin-angiotensin system (RAS) impairs the progression of chronic kidney disease (CKD). The aldosterone antagonist spironolactone has an antiproteinuric effect, but its use is limited by side effects. The present study evaluated the short term antiproteinuric effect and safety of the selective aldosterone antagonist eplerenone in non-diabetic CKD. STUDY DESIGN: Open randomized cross-over trial. SETTING AND PARTICIPANTS: Forty patients with non-diabetic CKD and urinary albumin excretion greater than 300 mg/24 hours. INTERVENTION: Eight weeks of once daily administration of add-on 25-50 mg eplerenone to stable standard antihypertensive treatment including RAS-blockade. OUTCOMES & MEASUREMENTS: 24 hour urinary albumin excretion, BP, p-potassium, and creatinine clearance. RESULTS: The mean urinary albumin excretion was 22% [CI: 14,28], P < 0.001, lower during treatment with eplerenone. Mean systolic BP was 4 mmHg [CI: 2,6], P = 0.002, diastolic BP was 2 mmHg [CI: 0,4], P = 0.02, creatinine clearance was 5% [CI: 2,8], P = 0.005, lower during eplerenone treatment. After correction for BP and creatinine clearance differences between the study periods, the mean urinary albumin excretion was 14% [CI: 4,24], P = 0.008 lower during treatment. Mean p potassium was 0.1 mEq/L [CI: 0.1,0.2] higher during eplerenone treatment, P<0.001. Eplerenone was thus well tolerated and no patients were withdrawn due to hyperkalaemia. LIMITATIONS: Open label, no wash-out period and a moderate sample size. CONCLUSIONS: In non-diabetic CKD patients, the addition of eplerenone to standard antihypertensive treatment including RAS-blockade caused a moderate BP independent fall in albuminuria, a minor fall in creatinine clearance and a 0.1 mEq/L increase in p-potassium. TRIAL REGISTRATION: Clinicaltrials.gov NCT00430924. PMID- 22073220 TI - Changes in clinical profile, treatment, and mortality in patients hospitalised for acute myocardial infarction between 1985 and 2008. AB - OBJECTIVES: To quantify the impact of the implementation of treatment modalities into clinical practice since 1985, on outcome of patients with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: All consecutive patients admitted for STEMI or NSTEMI at the Thoraxcenter between 1985 and 2008 were included. Baseline characteristics, pharmacological and invasive treatment modalities, and survival status were collected. The study population was categorised in three groups of patients: those hospitalised between 1985-1990, 1990-2000, and 2000-2008. RESULTS: We identified 14,434 patients hospitalised for myocardial infarction (MI). Both STEMI and NSTEMI patients were increasingly treated with the current guideline based therapy. In STEMI, at 30 days following admission, cumulative mortality rate decreased from 17% in 1985-1990 to 13% in 1990-2000, and to 6% in 2000-2008. Adjusted 30-day and three-year mortality in the last period was 80% and 68% lower than in 1985, respectively. In NSTEMI, at 30 days following admission, cumulative mortality rate decreased from 6% in 1985-1990 to 4% in 1990 2000, and to 2% in 2000-2008. Adjusted 30-day and three-year mortality in the last period was 78% and 49% lower than in 1985, respectively. For patients admitted between 2000 and 2008, 3 year survival of STEMI and NSTEMI patients was 87% and 88%, respectively. CONCLUSIONS: Our results indicate substantial improvements in acute- and long-term survival in patients hospitalised for MI, related to improved acute- as well as long-term treatment. Early medical evaluation in suspected MI and intensive early hospital treatment both remain warranted in the future. PMID- 22073221 TI - Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis. AB - BACKGROUND: Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs), representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease. METHODS AND FINDINGS: We tested this working hypothesis in amyotrophic lateral sclerosis (ALS) and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2) cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1) mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS), revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/Low)HLA-DR(-)CD33(+)) compared to controls. CONCLUSIONS: Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might represent a risk factor and a novel target for therapeutic intervention in ALS at least at the early stage. PMID- 22073222 TI - Carnivoran remains from the Malapa hominin site, South Africa. AB - Recent discoveries at the new hominin-bearing deposits of Malapa, South Africa, have yielded a rich faunal assemblage associated with the newly described hominin taxon Australopithecus sediba. Dating of this deposit using U-Pb and palaeomagnetic methods has provided an age of 1.977 Ma, being one of the most accurately dated, time constrained deposits in the Plio-Pleistocene of southern Africa. To date, 81 carnivoran specimens have been identified at this site including members of the families Canidae, Viverridae, Herpestidae, Hyaenidae and Felidae. Of note is the presence of the extinct taxon Dinofelis cf. D. barlowi that may represent the last appearance date for this species. Extant large carnivores are represented by specimens of leopard (Panthera pardus) and brown hyaena (Parahyaena brunnea). Smaller carnivores are also represented, and include the genera Atilax and Genetta, as well as Vulpes cf. V. chama. Malapa may also represent the first appearance date for Felis nigripes (Black-footed cat). The geochronological age of Malapa and the associated hominin taxa and carnivoran remains provide a window of research into mammalian evolution during a relatively unknown period in South Africa and elsewhere. In particular, the fauna represented at Malapa has the potential to elucidate aspects of the evolution of Dinofelis and may help resolve competing hypotheses about faunal exchange between East and Southern Africa during the late Pliocene or early Pleistocene. PMID- 22073223 TI - Phylogenetic and complementation analysis of a single-stranded DNA binding protein family from lactococcal phages indicates a non-bacterial origin. AB - BACKGROUND: The single-stranded-nucleic acid binding (SSB) protein superfamily includes proteins encoded by different organisms from Bacteria and their phages to Eukaryotes. SSB proteins share common structural characteristics and have been suggested to descend from an ancestor polypeptide. However, as other proteins involved in DNA replication, bacterial SSB proteins are clearly different from those found in Archaea and Eukaryotes. It was proposed that the corresponding genes in the phage genomes were transferred from the bacterial hosts. Recently new SSB proteins encoded by the virulent lactococcal bacteriophages (Orf14(bIL67) like proteins) have been identified and characterized structurally and biochemically. METHODOLOGY/PRINCIPAL FINDINGS: This study focused on the determination of phylogenetic relationships between Orf14(bIL67)-like proteins and other SSBs. We have performed a large scale phylogenetic analysis and pairwise sequence comparisons of SSB proteins from different phyla. The results show that, in remarkable contrast to other phage SSBs, the Orf14(bIL67)-like proteins form a distinct, self-contained and well supported phylogenetic group connected to the archaeal SSBs. Functional studies demonstrated that, despite the structural and amino acid sequence differences from bacterial SSBs, Orf14(bIL67) protein complements the conditional lethal ssb-1 mutation of Escherichia coli. CONCLUSIONS/SIGNIFICANCE: Here we identified for the first time a group of phages encoded SSBs which are clearly distinct from their bacterial counterparts. All methods supported the recognition of these phage proteins as a new family within the SSB superfamily. Our findings suggest that unlike other phages, the virulent lactococcal phages carry ssb genes that were not acquired from their hosts, but transferred from an archaeal genome. This represents a unique example of a horizontal gene transfer between Archaea and bacterial phages. PMID- 22073224 TI - Male germ cell-specific RNA binding protein RBMY: a new oncogene explaining male predominance in liver cancer. AB - Male gender is a risk factor for the development of hepatocellular carcinoma (HCC) but the mechanisms are not fully understood. The RNA binding motif gene on the Y chromosome (RBMY), encoding a male germ cell-specific RNA splicing regulator during spermatogenesis, is aberrantly activated in human male liver cancers. This study investigated the in vitro oncogenic effect and the possible mechanism of RBMY in human hepatoma cell line HepG2 and its in vivo effect with regards to the livers of human and transgenic mice. RBMY expression in HepG2 cells was knocked down by RNA interference and the cancer cell phenotype was characterized by soft-agar colony formation and sensitivity to hydrogen-peroxide induced apoptosis. The results revealed that RBMY knockdown reduced the transformation and anti-apoptotic efficiency of HepG2 cells. The expression of RBMY, androgen receptor (AR) and its inhibitory variant AR45, AR-targeted genes insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) was analyzed by quantitative RT-PCR. Up-regulation of AR45 variant and reduction of IGF-1 and IGFBP-3 expression was only detected in RBMY knockdown cells. Moreover, RBMY positive human male HCC expressed lower level of AR45 as compared to RBMY negative HCC tissues. The oncogenic properties of RBMY were further assessed in a transgenic mouse model. Liver-specific RBMY transgenic mice developed hepatic pre-cancerous lesions, adenoma, and HCC. RBMY also accelerated chemical carcinogen-induced hepatocarcinogenesis in transgenic mice. Collectively, these findings suggest that Y chromosome-specific RBMY is likely involved in the regulation of androgen receptor activity and contributes to male predominance of HCC. PMID- 22073225 TI - The circadian deadenylase Nocturnin is necessary for stabilization of the iNOS mRNA in mice. AB - Nocturnin is a member of the CCR4 deadenylase family, and its expression is under circadian control with peak levels at night. Because it can remove poly(A) tails from mRNAs, it is presumed to play a role in post-transcriptional control of circadian gene expression, but its target mRNAs are not known. Here we demonstrate that Nocturnin expression is acutely induced by the endotoxin lipopolysaccharide (LPS). Mouse embryo fibroblasts (MEFs) lacking Nocturnin exhibit normal patterns of acute induction of TNFalpha and iNOS mRNAs during the first three hours following LPS treatment, but by 24 hours, while TNFalpha mRNA levels are indistinguishable from WT cells, iNOS message is significantly reduced 20-fold. Accordingly, analysis of the stability of the mRNAs showed that loss of Nocturnin causes a significant decrease in the half-life of the iNOS mRNA (t(1/2) = 3.3 hours in Nocturnin knockout MEFs vs. 12.4 hours in wild type MEFs), while having no effect on the TNFalpha message. Furthermore, mice lacking Nocturnin lose the normal nighttime peak of hepatic iNOS mRNA, and have improved survival following LPS injection. These data suggest that Nocturnin has a novel stabilizing activity that plays an important role in the circadian response to inflammatory signals. PMID- 22073226 TI - Fasting induces the expression of PGC-1alpha and ERR isoforms in the outer stripe of the outer medulla (OSOM) of the mouse kidney. AB - BACKGROUND: Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha) is a member of the transcriptional coactivator family that plays a central role in the regulation of cellular energy metabolism under various physiological stimuli. During fasting, PGC-1alpha is induced in the liver and together with estrogen-related receptor a and gamma (ERRalpha and ERRgamma, orphan nuclear receptors with no known endogenous ligand, regulate sets of genes that participate in the energy balance program. We found that PGC-1alpha, ERRalpha and ERRgamma was highly expressed in human kidney HK2 cells and that PGC 1alpha induced dynamic protein interactions on the ERRalpha chromatin. However, the effect of fasting on the expression of endogenous PGC-1alpha, ERRalpha and ERRgamma in the kidney is not known. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrated by qPCR that the expression of PGC-1alpha, ERRalpha and ERRgamma was increased in the mouse kidney after fasting. By using immunohistochemistry (IHC), we showed these three proteins are co-localized in the outer stripe of the outer medulla (OSOM) of the mouse kidney. We were able to collect this region from the kidney using the Laser Capture Microdissection (LCM) technique. The qPCR data showed significant increase of PGC-1alpha, ERRalpha and ERRgamma mRNA in the LCM samples after fasting for 24 hours. Furthermore, the known ERRalpha target genes, mitochondrial oxidative phosphorylation gene COX8H and the tricarboxylic acid (TCA) cycle gene IDH3A also showed an increase. Taken together, our data suggest that fasting activates the energy balance program in the OSOM of the kidney. PMID- 22073227 TI - Dietary cholesterol-induced post-testicular infertility. AB - This work shows that an overload of dietary cholesterol causes complete infertility in dyslipidemic male mice (the Liver X Receptor-deficient mouse model). Infertility resulted from post-testicular defects affecting the fertilizing potential of spermatozoa. Spermatozoa of cholesterol-fed lxr-/- animals were found to be dramatically less viable and motile, and highly susceptible to undergo a premature acrosome reaction. We also provide evidence, that this lipid-induced infertility is associated with the accelerated appearance of a highly regionalized epididymal phenotype in segments 1 and 2 of the caput epididymidis that was otherwise only observed in aged LXR-deficient males. The epididymal epithelial phenotype is characterized by peritubular accumulation of cholesteryl ester lipid droplets in smooth muscle cells lining the epididymal duct, leading to their transdifferentiation into foam cells that eventually migrate through the duct wall, a situation that resembles the inflammatory atherosclerotic process. These findings establish the high level of susceptibility of epididymal sperm maturation to dietary cholesterol overload and could partly explain reproductive failures encountered by young dyslipidemic men as well as ageing males wishing to reproduce. PMID- 22073228 TI - N-terminal arginines modulate plasma-membrane localization of Kv7.1/KCNE1 channel complexes. AB - BACKGROUND AND OBJECTIVE: The slow delayed rectifier current (I(Ks)) is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 alpha-subunits and KCNE1 beta-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced I(Ks) and atrial fibrillation (a human arrhythmia). Structure-function relationship of the KCNE1 N-terminus for I(Ks) modulation is poorly understood and was subject of this study. METHODS: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines) at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. RESULTS: All KCNE1 constructs physically interacted with Kv7.1. I(Ks) resulting from co-expression of Kv7.1 with non-atrial fibrillation '38S' was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions ('38G-3xA') were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct ('Delta1-38'). Western blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. CONCLUSIONS: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of I(Ks). Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex. PMID- 22073229 TI - Impact of MUC1 mucin downregulation in the phenotypic characteristics of MKN45 gastric carcinoma cell line. AB - BACKGROUND: Gastric carcinoma is the second leading cause of cancer-associated death worldwide. The high mortality associated with this disease is in part due to limited knowledge about gastric carcinogenesis and a lack of available therapeutic and prevention strategies. MUC1 is a high molecular weight transmembrane mucin protein expressed at the apical surface of most glandular epithelial cells and a major component of the mucus layer above gastric mucosa. Overexpression of MUC1 is found in approximately 95% of human adenocarcinomas, where it is associated with oncogenic activity. The role of MUC1 in gastric cancer progression remains to be clarified. METHODOLOGY: We downregulated MUC1 expression in a gastric carcinoma cell line by RNA interference and studied the effects on cellular proliferation (MTT assay), apoptosis (TUNEL assay), migration (migration assay), invasion (invasion assay) and aggregation (aggregation assay). Global gene expression was evaluated by microarray analysis to identify alterations that are regulated by MUC1 expression. In vivo assays were also performed in mice, in order to study the tumorigenicity of cells with and without MUC1 downregulation in MKN45 gastric carcinoma cell line. RESULTS: Downregulation of MUC1 expression increased proliferation and apoptosis as compared to controls, whereas cell-cell aggregation was decreased. No significant differences were found in terms of migration and invasion between the downregulated clones and the controls. Expression of TCN1, KLK6, ADAM29, LGAL4, TSPAN8 and SHPS-1 was found to be significantly different between MUC1 downregulated clones and the control cells. In vivo assays have shown that mice injected with MUC1 downregulated cells develop smaller tumours when compared to mice injected with the control cells. CONCLUSIONS: These results indicate that MUC1 downregulation alters the phenotype and tumorigenicity of MKN45 gastric carcinoma cells and also the expression of several molecules that can be involved in tumorigenic events. Therefore, MUC1 should be further studied to better clarify its potential as a novel therapeutic target for gastric cancer. PMID- 22073230 TI - Methionine sulfoxide reductases are essential for virulence of Salmonella typhimurium. AB - Production of reactive oxygen species represents a fundamental innate defense against microbes in a diversity of host organisms. Oxidative stress, amongst others, converts peptidyl and free methionine to a mixture of methionine-S- (Met S-SO) and methionine-R-sulfoxides (Met-R-SO). To cope with such oxidative damage, methionine sulfoxide reductases MsrA and MsrB are known to reduce MetSOs, the former being specific for the S-form and the latter being specific for the R form. However, at present the role of methionine sulfoxide reductases in the pathogenesis of intracellular bacterial pathogens has not been fully detailed. Here we show that deletion of msrA in the facultative intracellular pathogen Salmonella (S.) enterica serovar Typhimurium increased susceptibility to exogenous H(2)O(2), and reduced bacterial replication inside activated macrophages, and in mice. In contrast, a DeltamsrB mutant showed the wild type phenotype. Recombinant MsrA was active against free and peptidyl Met-S-SO, whereas recombinant MsrB was only weakly active and specific for peptidyl Met-R SO. This raised the question of whether an additional Met-R-SO reductase could play a role in the oxidative stress response of S. Typhimurium. MsrC is a methionine sulfoxide reductase previously shown to be specific for free Met-R-SO in Escherichia (E.) coli. We tested a DeltamsrC single mutant and a DeltamsrBDeltamsrC double mutant under various stress conditions, and found that MsrC is essential for survival of S. Typhimurium following exposure to H(2)O(2,) as well as for growth in macrophages, and in mice. Hence, this study demonstrates that all three methionine sulfoxide reductases, MsrA, MsrB and MsrC, facilitate growth of a canonical intracellular pathogen during infection. Interestingly MsrC is specific for the repair of free methionine sulfoxide, pointing to an important role of this pathway in the oxidative stress response of Salmonella Typhimurium. PMID- 22073231 TI - NFX1-LIKE2 (NFXL2) suppresses abscisic acid accumulation and stomatal closure in Arabidopsis thaliana. AB - The NFX1-LIKE1 (NFXL1) and NFXL2 genes were identified as regulators of salt stress responses. The NFXL1 protein is a nuclear factor that positively affects adaptation to salt stress. The nfxl1-1 loss-of-function mutant displayed reduced survival rates under salt and high light stress. In contrast, the nfxl2-1 mutant, defective in the NFXL2 gene, and NFXL2-antisense plants exhibited enhanced survival under these conditions. We show here that the loss of NFXL2 function results in abscisic acid (ABA) overaccumulation, reduced stomatal conductance, and enhanced survival under drought stress. The nfxl2-1 mutant displayed reduced stomatal aperture under all conditions tested. Fusicoccin treatment, exposition to increasing light intensities, and supply of decreasing CO(2) concentrations demonstrated full opening capacity of nfxl2-1 stomata. Reduced stomatal opening presumably is a consequence of elevated ABA levels. Furthermore, seedling growth, root growth, and stomatal closure were hypersensitive to exogenous ABA. The enhanced ABA responses may contribute to the improved drought stress resistance of the mutant. Three NFXL2 splice variants were cloned and named NFXL2-78, NFXL2 97, and NFXL2-100 according to the molecular weight of the putative proteins. Translational fusions to the green fluorescent protein suggest nuclear localisation of the NFXL2 proteins. Stable expression of the NFXL2-78 splice variant in nfxl2-1 plants largely complemented the mutant phenotype. Our data show that NFXL2 controls ABA levels and suppresses ABA responses. NFXL2 may prevent unnecessary and costly stress adaptation under favourable conditions. PMID- 22073232 TI - Transcriptomics responses in marine diatom Thalassiosira pseudonana exposed to the polycyclic aromatic hydrocarbon benzo[a]pyrene. AB - Diatoms are unicellular, photosynthetic, eukaryotic algae with a ubiquitous distribution in water environments and they play an important role in the carbon cycle. Molecular or morphological changes in these species under ecological stress conditions are expected to serve as early indicators of toxicity and can point to a global impact on the entire ecosystem. Thalassiosira pseudonana, a marine diatom and the first with a fully sequenced genome has been selected as an aquatic model organism for ecotoxicological studies using molecular tools. A customized DNA microarray containing probes for the available gene sequences has been developed and tested to analyze the effects of a common pollutant, benzo(a)pyrene (BaP), at a sub-lethal concentration. This approach in diatoms has helped to elucidate pathway/metabolic processes involved in the mode of action of this pollutant, including lipid metabolism, silicon metabolism and stress response. A dose-response of BaP on diatoms has been made and the effect of this compound on the expression of selected genes was assessed by quantitative real time-PCR. Up-regulation of the long-chain acyl-CoA synthetase and the anti apoptotic transmembrane Bax inhibitor, as well as down-regulation of silicon transporter 1 and a heat shock factor was confirmed at lower concentrations of BaP, but not the heat-shock protein 20. The study has allowed the identification of molecular biomarkers to BaP to be later on integrated into environmental monitoring for water quality assessment. PMID- 22073233 TI - Corruption kills: estimating the global impact of corruption on children deaths. AB - BACKGROUND: Information on the global risk factors of children mortality is crucial to guide global efforts to improve survival. Corruption has been previously shown to significantly impact on child mortality. However no recent quantification of its current impact is available. METHODS: The impact of corruption was assessed through crude Pearson's correlation, univariate and multivariate linear models coupling national under-five mortality rates in 2008 to the national "perceived level of corruption" (CPI) and a large set of adjustment variables measured during the same period. FINDINGS: The final multivariable model (adjusted R(2)= 0.89) included the following significant variables: percentage of people with improved sanitation (p.value<0.001), logarithm of total health expenditure (p.value = 0.006), Corruption Perception Index (p.value<0.001), presence of an arid climate on the national territory (p = 0.006), and the dependency ratio (p.value<0.001). A decrease in CPI of one point (i.e. a more important perceived corruption) was associated with an increase in the log of national under-five mortality rate of 0.0644. According to this result, it could be roughly hypothesized that more than 140000 annual children deaths could be indirectly attributed to corruption. INTERPRETATIONS: Global response to children mortality must involve a necessary increase in funds available to develop water and sanitation access and purchase new methods for prevention, management, and treatment of major diseases drawing the global pattern of children deaths. However without paying regard to the anti-corruption mechanisms needed to ensure their proper use, it will also provide further opportunity for corruption. Policies and interventions supported by governments and donors must integrate initiatives that recognise how they are inter-related. PMID- 22073234 TI - Granulovacuolar degenerations appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders. AB - BACKGROUND: Granulovacuolar degeneration (GVD) is one of the pathological hallmarks of Alzheimer's disease (AD), and it is defined as electron-dense granules within double membrane-bound cytoplasmic vacuoles. Several lines of evidence have suggested that GVDs appear within hippocampal pyramidal neurons in AD when phosphorylated tau begins to aggregate into early-stage neurofibrillary tangles. The aim of this study is to investigate the association of GVDs with phosphorylated tau pathology to determine whether GVDs and phosphorylated tau coexist among different non-AD neurodegenerative disorders. METHODS: An autopsied series of 28 patients with a variety of neurodegenerative disorders and 9 control patients were evaluated. Standard histological stains along with immunohistochemistry using protein markers for GVD and confocal microscopy were utilized. RESULTS: The number of neurons with GVDs significantly increased with the level of phosphorylated tau accumulation in the hippocampal regions in non-AD neurodegenerative disorders. At the cellular level, diffuse staining for phosphorylated tau was detected in neurons with GVDs. CONCLUSIONS: Our data suggest that GVDs appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders, while the presence of phosphorylated tau in GVD-harbouring neurons in non-AD neurodegenerative disorders was indistinguishable from age-related accumulation of phosphorylated tau. Although GVDs in non-AD neurodegenerative disorders have not been studied thoroughly, our results suggest that they are not incidental findings, but rather they appear in relation to phosphorylated tau accumulation, further highlighting the role of GVD in the process of phosphorylated tau accumulation. PMID- 22073236 TI - Climate change impact on neotropical social wasps. AB - Establishing a direct link between climate change and fluctuations in animal populations through long-term monitoring is difficult given the paucity of baseline data. We hypothesized that social wasps are sensitive to climatic variations, and thus studied the impact of ENSO events on social wasp populations in French Guiana. We noted that during the 2000 La Nina year there was a 77.1% decrease in their nest abundance along ca. 5 km of forest edges, and that 70.5% of the species were no longer present. Two simultaneous 13-year surveys (1997 2009) confirmed the decrease in social wasps during La Nina years (2000 and 2006), while an increase occurred during the 2009 El Nino year. A 30-year weather survey showed that these phenomena corresponded to particularly high levels of rainfall, and that temperature, humidity and global solar radiation were correlated with rainfall. Using the Self-Organizing Map algorithm, we show that heavy rainfall during an entire rainy season has a negative impact on social wasps. Strong contrasts in rainfall between the dry season and the short rainy season exacerbate this effect. Social wasp populations never recovered to their pre-2000 levels. This is probably because these conditions occurred over four years; heavy rainfall during the major rainy seasons during four other years also had a detrimental effect. On the contrary, low levels of rainfall during the major rainy season in 2009 spurred an increase in social wasp populations. We conclude that recent climatic changes have likely resulted in fewer social wasp colonies because they have lowered the wasps' resistance to parasitoids and pathogens. These results imply that Neotropical social wasps can be regarded as bio-indicators because they highlight the impact of climatic changes not yet perceptible in plants and other animals. PMID- 22073235 TI - Differential expression of Wnts after spinal cord contusion injury in adult rats. AB - BACKGROUND: Spinal cord injury is a major cause of disability that has no clinically accepted treatment. Functional decline following spinal cord injury is caused by mechanical damage, secondary cell death, reactive gliosis and a poor regenerative capacity of damaged axons. Wnt proteins are a family of secreted glycoproteins that play key roles in different developmental processes although little is known of the expression patterns and functions of Wnts in the adult central nervous system in normal or diseased states. FINDINGS: Using qRT-PCR analysis, we demonstrate that mRNA encoding most Wnt ligands and soluble inhibitors are constitutively expressed in the healthy adult spinal cord. Strikingly, contusion spinal cord injury induced a time-dependent increase in Wnt mRNA expression from 6 hours until 28 days post-injury, and a narrow peak in the expression of soluble Wnt inhibitors between 1 and 3 days post-injury. These results are consistent with the increase in the migration shift, from day 1 to 7, of the intracellular Wnt signalling component, Dishevelled-3. Moreover, after an initial decrease by 1 day, we also found an increase in phosphorylation of the Wnt co-receptor, low-density lipoprotein receptor-related protein 6, and an increase in active beta-catenin protein, both of which suffer a dramatic change, from a homogeneous expression pattern in the grey matter to a disorganized injury induced pattern. CONCLUSIONS: Our results suggest a role for Wnts in spinal cord homeostasis and injury. We demonstrate that after injury Wnt signalling is activated via the Wnt/beta-catenin and possibly other pathways. These findings provide an important foundation to further address the function of individual Wnt proteins in vivo and the pathophysiology of spinal cord injury. PMID- 22073237 TI - Mangafodipir protects against hepatic ischemia-reperfusion injury in mice. AB - INTRODUCTION AND AIM: Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. METHODS: Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. RESULTS: Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. CONCLUSIONS: Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury. PMID- 22073238 TI - MiR-223 suppresses cell proliferation by targeting IGF-1R. AB - To study the roles of microRNA-223 (miR-223) in regulation of cell growth, we established a miR-223 over-expression model in HeLa cells infected with miR-223 by Lentivirus pLL3.7 system. We observed in this model that miR-223 significantly suppressed the proliferation, growth rate, colony formation of HeLa cells in vitro, and in vivo tumorigenicity or tumor formation in nude mice. To investigate the mechanisms involved, we scanned and examined the potential and putative target molecules of miR-223 by informatics, quantitative PCR and Western blot, and found that insulin-like growth factor-1 receptor (IGF-1R) was the functional target of miR-223 inhibition of cell proliferation. Targeting IGF-1R by miR-223 was not only seen in HeLa cells, but also in leukemia and hepatoma cells. The downstream pathway, Akt/mTOR/p70S6K, to which the signal was mediated by IGF-1R, was inhibited as well. The relative luciferase activity of the reporter containing wild-type 3'UTR(3'untranslated region) of IGF-1R was significantly suppressed, but the mutant not. Silence of IGF-1R expression by vector-based short hairpin RNA resulted in the similar inhibition with miR-223. Contrarily, rescued IGF-1R expression in the cells that over-expressed miR-223, reversed the inhibition caused by miR-223 via introducing IGF-1R cDNA that didn't contain the 3'UTR. Meanwhile, we also noted that miR-223 targeted Rasa1, but the downstream molecules mediated by Rasa1 was neither targeted nor regulated. Therefore we believed that IGF-1R was the functional target for miR-223 suppression of cell proliferation and its downstream PI3K/Akt/mTOR/p70S6K pathway suppressed by miR 223 was by targeting IGF-1R. PMID- 22073239 TI - Modeling the mechanism of action of a DGAT1 inhibitor using a causal reasoning platform. AB - Triglyceride accumulation is associated with obesity and type 2 diabetes. Genetic disruption of diacylglycerol acyltransferase 1 (DGAT1), which catalyzes the final reaction of triglyceride synthesis, confers dramatic resistance to high-fat diet induced obesity. Hence, DGAT1 is considered a potential therapeutic target for treating obesity and related metabolic disorders. However, the molecular events shaping the mechanism of action of DGAT1 pharmacological inhibition have not been fully explored yet. Here, we investigate the metabolic molecular mechanisms induced in response to pharmacological inhibition of DGAT1 using a recently developed computational systems biology approach, the Causal Reasoning Engine (CRE). The CRE algorithm utilizes microarray transcriptomic data and causal statements derived from the biomedical literature to infer upstream molecular events driving these transcriptional changes. The inferred upstream events (also called hypotheses) are aggregated into biological models using a set of analytical tools that allow for evaluation and integration of the hypotheses in context of their supporting evidence. In comparison to gene ontology enrichment analysis which pointed to high-level changes in metabolic processes, the CRE results provide detailed molecular hypotheses to explain the measured transcriptional changes. CRE analysis of gene expression changes in high fat habituated rats treated with a potent and selective DGAT1 inhibitor demonstrate that the majority of transcriptomic changes support a metabolic network indicative of reversal of high fat diet effects that includes a number of molecular hypotheses such as PPARG, HNF4A and SREBPs. Finally, the CRE-generated molecular hypotheses from DGAT1 inhibitor treated rats were found to capture the major molecular characteristics of DGAT1 deficient mice, supporting a phenotype of decreased lipid and increased insulin sensitivity. PMID- 22073240 TI - Suicidal behavior and depression in smoking cessation treatments. AB - BACKGROUND: Two treatments for smoking cessation--varenicline and bupropion- carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown. METHODOLOGY: From the FDA's Adverse Event Reporting System (AERS) database from 1998 through September 2010 we selected domestic, serious case reports for varenicline (n = 9,575), bupropion for smoking cessation (n = 1,751), and nicotine replacement products (n = 1,917). A composite endpoint of suicidal/self-injurious behavior or depression was defined as a case with one or more Preferred Terms in Standardized MedDRA Query (SMQ) for those adverse effects. The main outcome measure was the ratio of reported suicide/self-injury or depression cases for each drug compared to all other serious events for that drug. RESULTS: Overall we identified 3,249 reported cases of suicidal/self-injurious behavior or depression, 2,925 (90%) for varenicline, 229 (7%) for bupropion, and 95 (3%) for nicotine replacement. Compared to nicotine replacement, the disproportionality results (OR (95% CI)) were varenicline 8.4 (6.8-10.4), and bupropion 2.9 (2.3-3.7). The disproportionality persisted after excluding reports indicating concomitant therapy with any of 58 drugs with suicidal behavior warnings or precautions in the prescribing information. An additional antibiotic comparison group showed that adverse event reports of suicidal/self-injurious behavior or depression were otherwise rare in a healthy population receiving short-term drug treatment. CONCLUSIONS: Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation. PMID- 22073241 TI - The role of speciation in positive Lowenstein-Jensen culture isolates from a high tuberculosis burden country. AB - OBJECTIVE: To determine the need for routine speciation of positive Lowenstein Jensen mycobacterial cultures in HIV-infected patients suspected of having pulmonary tuberculosis at Mulago Hospital in Kampala, Uganda. METHODS: Sputum and bronchoalveolar lavage Lowenstein-Jensen mycobacterial culture isolates from consecutive, HIV-infected patients admitted to Mulago Hospital with 2 weeks or more of cough were subjected to IS6110 PCR and rpoB genetic analysis to determine the presence of Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM). RESULTS: Eighty (100%) mycobacterial cultures from 65 patients were confirmed to be members of MTBC. Subsequent analysis of the cultures from 54 patients by PCR and sequence analyses to identify co-infection with NTM confirmed the presence of MTBC as well as the presence of Micrococcus luteus (n = 4), Janibacter spp. (n = 1) and six cultures had organisms that could not be identified. CONCLUSIONS: Presumptive diagnosis of tuberculosis on the basis of a positive Lowenstein-Jensen culture is sufficient in HIV-infected Ugandans suspected of having tuberculosis. Routine molecular confirmation of positive Lowenstein-Jensen cultures is unnecessary in this low resource setting. PMID- 22073242 TI - Phase I evaluation of STA-1474, a prodrug of the novel HSP90 inhibitor ganetespib, in dogs with spontaneous cancer. AB - BACKGROUND: The novel water soluble compound STA-1474 is metabolized to ganetespib (formerly STA-9090), a potent HSP90 inhibitor previously shown to kill canine tumor cell lines in vitro and inhibit tumor growth in the setting of murine xenografts. The purpose of the following study was to extend these observations and investigate the safety and efficacy of STA-1474 in dogs with spontaneous tumors. METHODS AND FINDINGS: This was a Phase 1 trial in which dogs with spontaneous tumors received STA-1474 under one of three different dosing schemes. Pharmacokinetics, toxicities, biomarker changes, and tumor responses were assessed. Twenty-five dogs with a variety of cancers were enrolled. Toxicities were primarily gastrointestinal in nature consisting of diarrhea, vomiting, inappetence and lethargy. Upregulation of HSP70 protein expression was noted in both tumor specimens and PBMCs within 7 hours following drug administration. Measurable objective responses were observed in dogs with malignant mast cell disease (n = 3), osteosarcoma (n = 1), melanoma (n = 1) and thyroid carcinoma (n = 1), for a response rate of 24% (6/25). Stable disease (>10 weeks) was seen in 3 dogs, for a resultant overall biological activity of 36% (9/25). CONCLUSIONS: This study provides evidence that STA-1474 exhibits biologic activity in a relevant large animal model of cancer. Given the similarities of canine and human cancers with respect to tumor biology and HSP90 activation, it is likely that STA-1474 and ganetespib will demonstrate comparable anti-cancer activity in human patients. PMID- 22073243 TI - The two Caenorhabditis elegans UDP-glucose:glycoprotein glucosyltransferase homologues have distinct biological functions. AB - The UDP-Glc:glycoprotein glucosyltransferase (UGGT) is the sensor of glycoprotein conformations in the glycoprotein folding quality control as it exclusively glucosylates glycoproteins not displaying their native conformations. Monoglucosylated glycoproteins thus formed may interact with the lectin chaperones calnexin (CNX) and calreticulin (CRT). This interaction prevents premature exit of folding intermediates to the Golgi and enhances folding efficiency. Bioinformatic analysis showed that in C. elegans there are two open reading frames (F48E3.3 and F26H9.8 to be referred as uggt-1 and uggt-2, respectively) coding for UGGT homologues. Expression of both genes in Schizosaccharomyces pombe mutants devoid of UGGT activity showed that uggt-1 codes for an active UGGT protein (CeUGGT-1). On the other hand, uggt-2 coded for a protein (CeUGGT-2) apparently not displaying a canonical UGGT activity. This protein was essential for viability, although cnx/crt null worms were viable. We constructed transgenic worms carrying the uggt-1 promoter linked to the green fluorescent protein (GFP) coding sequence and found that CeUGGT-1 is expressed in cells of the nervous system. uggt-1 is upregulated under ER stress through the ire-1 arm of the unfolded protein response (UPR). Real-time PCR analysis showed that both uggt-1 and uggt-2 genes are expressed during the entire C. elegans life cycle. RNAi-mediated depletion of CeUGGT-1 but not of CeUGGT-2 resulted in a reduced lifespan and that of CeUGGT-1 and CeUGGT-2 in a developmental delay. We found that both CeUGGT1 and CeUGGT2 play a protective role under ER stress conditions, since 10 ug/ml tunicamycin arrested development at the L2/L3 stage of both uggt-1(RNAi) and uggt-2(RNAi) but not of control worms. Furthermore, we found that the role of CeUGGT-2 but not CeUGGT-1 is significant in relieving low ER stress levels in the absence of the ire-1 unfolding protein response signaling pathway. Our results indicate that both C. elegans UGGT homologues have distinct biological functions. PMID- 22073244 TI - Testing the water-energy theory on American palms (Arecaceae) using geographically weighted regression. AB - Water and energy have emerged as the best contemporary environmental correlates of broad-scale species richness patterns. A corollary hypothesis of water-energy dynamics theory is that the influence of water decreases and the influence of energy increases with absolute latitude. We report the first use of geographically weighted regression for testing this hypothesis on a continuous species richness gradient that is entirely located within the tropics and subtropics. The dataset was divided into northern and southern hemispheric portions to test whether predictor shifts are more pronounced in the less oceanic northern hemisphere. American palms (Arecaceae, n = 547 spp.), whose species richness and distributions are known to respond strongly to water and energy, were used as a model group. The ability of water and energy to explain palm species richness was quantified locally at different spatial scales and regressed on latitude. Clear latitudinal trends in agreement with water-energy dynamics theory were found, but the results did not differ qualitatively between hemispheres. Strong inherent spatial autocorrelation in local modeling results and collinearity of water and energy variables were identified as important methodological challenges. We overcame these problems by using simultaneous autoregressive models and variation partitioning. Our results show that the ability of water and energy to explain species richness changes not only across large climatic gradients spanning tropical to temperate or arctic zones but also within megathermal climates, at least for strictly tropical taxa such as palms. This finding suggests that the predictor shifts are related to gradual latitudinal changes in ambient energy (related to solar flux input) rather than to abrupt transitions at specific latitudes, such as the occurrence of frost. PMID- 22073245 TI - Finding and testing network communities by lumped Markov chains. AB - Identifying communities (or clusters), namely groups of nodes with comparatively strong internal connectivity, is a fundamental task for deeply understanding the structure and function of a network. Yet, there is a lack of formal criteria for defining communities and for testing their significance. We propose a sharp definition that is based on a quality threshold. By means of a lumped Markov chain model of a random walker, a quality measure called "persistence probability" is associated to a cluster, which is then defined as an "alpha community" if such a probability is not smaller than alpha. Consistently, a partition composed of alpha-communities is an "alpha-partition." These definitions turn out to be very effective for finding and testing communities. If a set of candidate partitions is available, setting the desired alpha-level allows one to immediately select the alpha-partition with the finest decomposition. Simultaneously, the persistence probabilities quantify the quality of each single community. Given its ability in individually assessing each single cluster, this approach can also disclose single well-defined communities even in networks that overall do not possess a definite clusterized structure. PMID- 22073246 TI - Adapted to roar: functional morphology of tiger and lion vocal folds. AB - Vocal production requires active control of the respiratory system, larynx and vocal tract. Vocal sounds in mammals are produced by flow-induced vocal fold oscillation, which requires vocal fold tissue that can sustain the mechanical stress during phonation. Our understanding of the relationship between morphology and vocal function of vocal folds is very limited. Here we tested the hypothesis that vocal fold morphology and viscoelastic properties allow a prediction of fundamental frequency range of sounds that can be produced, and minimal lung pressure necessary to initiate phonation. We tested the hypothesis in lions and tigers who are well-known for producing low frequency and very loud roaring sounds that expose vocal folds to large stresses. In histological sections, we found that the Panthera vocal fold lamina propria consists of a lateral region with adipocytes embedded in a network of collagen and elastin fibers and hyaluronan. There is also a medial region that contains only fibrous proteins and hyaluronan but no fat cells. Young's moduli range between 10 and 2000 kPa for strains up to 60%. Shear moduli ranged between 0.1 and 2 kPa and differed between layers. Biomechanical and morphological data were used to make predictions of fundamental frequency and subglottal pressure ranges. Such predictions agreed well with measurements from natural phonation and phonation of excised larynges, respectively. We assume that fat shapes Panthera vocal folds into an advantageous geometry for phonation and it protects vocal folds. Its primary function is probably not to increase vocal fold mass as suggested previously. The large square-shaped Panthera vocal fold eases phonation onset and thereby extends the dynamic range of the voice. PMID- 22073247 TI - Vision is adapted to the natural level of blur present in the retinal image. AB - BACKGROUND: The image formed by the eye's optics is inherently blurred by aberrations specific to an individual's eyes. We examined how visual coding is adapted to the optical quality of the eye. METHODS AND FINDINGS: We assessed the relationship between perceived blur and the retinal image blur resulting from high order aberrations in an individual's optics. Observers judged perceptual blur in a psychophysical two-alternative forced choice paradigm, on stimuli viewed through perfectly corrected optics (using a deformable mirror to compensate for the individual's aberrations). Realistic blur of different amounts and forms was computer simulated using real aberrations from a population. The blur levels perceived as best focused were close to the levels predicted by an individual's high order aberrations over a wide range of blur magnitudes, and were systematically biased when observers were instead adapted to the blur reproduced from a different observer's eye. CONCLUSIONS: Our results provide strong evidence that spatial vision is calibrated for the specific blur levels present in each individual's retinal image and that this adaptation at least partly reflects how spatial sensitivity is normalized in the neural coding of blur. PMID- 22073248 TI - The interaction between regulatory T cells and NKT cells in the liver: a CD1d bridge links innate and adaptive immunity. AB - BACKGROUND/AIMS: Regulatory T cells (Tregs) and natural killer T (NKT) cells are two distinct lymphocyte subsets that independently regulate hepatic adaptive and innate immunity, respectively. In the current study, we examine the interaction between Tregs and NKT cells to understand the mechanisms of cross immune regulation by these cells. METHODS: The frequency and function of Tregs were evaluated in wild type and NKT cell deficient (CD1dko) mice. In vitro lymphocyte proliferation and apoptosis assays were performed with NKT cells co-cultured with Tregs. The ability of Tregs to inhibit NKT cells in vivo was examined by adoptive transfer of Tregs in a model of NKT cell mediated hepatitis. RESULTS: CD1dko mice have a significant reduction in hepatic Tregs. Although, the Tregs from CD1dko mice remain functional and can suppress conventional T cells, their ability to suppress activation induced NKT cell proliferation and to promote NKT cell apoptosis is greatly diminished. These effects are CD1d dependent and require cell to cell contact. Adoptive transfer of Tregs inhibits NKT cell-mediated liver injury. CONCLUSIONS: NKT cells promote Tregs, and Tregs inhibit NKT cells in a CD1d dependent manner requiring cell to cell contact. These cross-talk immune regulations provide a linkage between innate and adaptive immunity. PMID- 22073249 TI - Up-regulation of MUC2 and IL-1beta expression in human colonic epithelial cells by Shigella and its interaction with mucins. AB - BACKGROUND: The entire gastrointestinal tract is protected by a mucous layer, which contains complex glycoproteins called mucins. MUC2 is one such mucin that protects the colonic mucosa from invading microbes. The initial interaction between microbes and mucins is an important step for microbial pathogenesis. Hence, it was of interest to investigate the relationship between host (mucin) and pathogen interaction, including Shigella induced expression of MUC2 and IL 1beta during shigellosis. METHODS: The mucin-Shigella interaction was revealed by an in vitro mucin-binding assay. Invasion of Shigella dysenteriae into HT-29 cells was analyzed by Transmission electron microscopy. Shigella induced mucin and IL-1beta expression were analyzed by RT-PCR and Immunofluorescence. RESULTS: The clinical isolates of Shigella were found to be virulent by a congo-red binding assay. The in vitro mucin-binding assay revealed both Shigella dysenteriae and Shigella flexneri have binding affinity in the increasing order of: guinea pig small intestinal mucin2 years). HRM scores were generated for two regions in gag, one region in pol, and three regions in env. RESULTS: Median HRM scores were higher in non-recent infection than in recent infection for all six regions tested. In multivariate models, higher HRM scores in three of the six regions were independently associated with non-recent HIV infection. CONCLUSIONS: The HRM diversity assay provides a simple, scalable method for measuring HIV diversity. HRM scores, which reflect the genetic diversity in a viral population, may be useful biomarkers for evaluation of HIV incidence, particularly if multiple regions of the HIV genome are examined. PMID- 22073291 TI - Helicobacter pylori genotyping from American indigenous groups shows novel Amerindian vacA and cagA alleles and Asian, African and European admixture. AB - It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America. PMID- 22073292 TI - Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells. AB - Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC) transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3 bromopyruvate (3BrPA) suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2), KG-1 (ABCB1) and HepG2 cells (ABCB1 and ABCG2). Interestingly, although side population (SP) cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG 1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells. PMID- 22073293 TI - Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression. AB - Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic alternative strategy to enhance host innate immunity and disease resistance. PMID- 22073294 TI - Profiling of substrate specificities of 3C-like proteases from group 1, 2a, 2b, and 3 coronaviruses. AB - BACKGROUND: Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL(pro)), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: Here, we profiled the substrate specificities of 3CL(pro) from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19 * 8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL(pro) prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL(pro) from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL(pro) prefers P4-Pro and SARS-CoV 3CL(pro) prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences 'VARLQ?SGF' that can be cleaved efficiently by all 3CL(pro) with relative activity of 1.7 to 3.2, and 'VPRLQ?SGF' that can be cleaved specifically by IBV 3CL(pro) with relative activity of 4.3. CONCLUSIONS/SIGNIFICANCE: The comprehensive substrate specificities of 3CL(pro) from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases. PMID- 22073295 TI - Protozoan parasite Toxoplasma gondii manipulates mate choice in rats by enhancing attractiveness of males. AB - Females in various species typically avoid males infected with parasites, while parasite-free males advertise their status through conspicuous phenotypic traits. This process selects for heritable resistance and reduces direct exposure of the female to parasites. Coevolving parasites are likely to attempt to circumvent this obstacle. In this paper, we demonstrate a case of parasitic manipulation of host mate choice. We report that Toxoplasma gondii, a sexually transmitted infection of brown rats, enhances sexual attractiveness of infected males. Thus under some evolutionary niches, parasites can indeed manipulate host sexual signaling to their own advantage. PMID- 22073296 TI - Oscillatory protein expression dynamics endows stem cells with robust differentiation potential. AB - The lack of understanding of stem cell differentiation and proliferation is a fundamental problem in developmental biology. Although gene regulatory networks (GRNs) for stem cell differentiation have been partially identified, the nature of differentiation dynamics and their regulation leading to robust development remain unclear. Herein, using a dynamical system modeling cell approach, we performed simulations of the developmental process using all possible GRNs with a few genes, and screened GRNs that could generate cell type diversity through cell cell interactions. We found that model stem cells that both proliferated and differentiated always exhibited oscillatory expression dynamics, and the differentiation frequency of such stem cells was regulated, resulting in a robust number distribution. Moreover, we uncovered the common regulatory motifs for stem cell differentiation, in which a combination of regulatory motifs that generated oscillatory expression dynamics and stabilized distinct cellular states played an essential role. These findings may explain the recently observed heterogeneity and dynamic equilibrium in cellular states of stem cells, and can be used to predict regulatory networks responsible for differentiation in stem cell systems. PMID- 22073297 TI - Generation of micronuclei during interphase by coupling between cytoplasmic membrane blebbing and nuclear budding. AB - Micronucleation, mediated by interphase nuclear budding, has been repeatedly suggested, but the process is still enigmatic. In the present study, we confirmed the previous observation that there are lamin B1-negative micronuclei in addition to the positive ones. A large cytoplasmic bleb was found to frequently entrap lamin B1-negative micronuclei, which were connected to the nucleus by a thin chromatin stalk. At the bottom of the stalk, the nuclear lamin B1 structure appeared broken. Chromatin extrusion through lamina breaks has been referred to as herniation or a blister of the nucleus, and has been observed after the expression of viral proteins. A cell line in which extrachromosomal double minutes and lamin B1 protein were simultaneously visualized in different colors in live cells was established. By using these cells, time-lapse microscopy revealed that cytoplasmic membrane blebbing occurred simultaneously with the extrusion of nuclear content, which generated lamin B1-negative micronuclei during interphase. Furthermore, activation of cytoplasmic membrane blebbing by the addition of fresh serum or camptothecin induced nuclear budding within 1 to 10 minutes, which suggested that blebbing might be the cause of the budding. After the induction of blebbing, the frequency of lamin-negative micronuclei increased. The budding was most frequent during S phase and more efficiently entrapped small extrachromosomal chromatin than the large chromosome arm. Based on these results, we suggest a novel mechanism in which cytoplasmic membrane dynamics pulls the chromatin out of the nucleus through the lamina break. Evidence for such a mechanism was obtained in certain cancer cell lines including human COLO 320 and HeLa. The mechanism could significantly perturb the genome and influence cancer cell phenotypes. PMID- 22073298 TI - Characterization of a novel type of HIV-1 particle assembly inhibitor using a quantitative luciferase-Vpr packaging-based assay. AB - The HIV-1 auxiliary protein Vpr and Vpr-fusion proteins can be copackaged with Gag precursor (Pr55Gag) into virions or membrane-enveloped virus-like particles (VLP). Taking advantage of this property, we developed a simple and sensitive method to evaluate potential inhibitors of HIV-1 assembly in a living cell system. Two proteins were coexpressed in recombinant baculovirus-infected Sf9 cells, Pr55Gag, which formed the VLP backbone, and luciferase fused to the N terminus of Vpr (LucVpr). VLP-encapsidated LucVpr retained the enzymatic activity of free luciferase. The levels of luciferase activity present in the pelletable fraction recovered from the culture medium correlated with the amounts of extracellular VLP released by Sf9 cells assayed by conventional immunological methods. Our luciferase-based assay was then applied to the characterization of betulinic acid (BA) derivatives that differed from the leader compound PA-457 (or DSB) by their substituant on carbon-28. The beta-alanine-conjugated and lysine conjugated DSB could not be evaluated for their antiviral potentials due to their high cytotoxicity, whereas two other compounds with a lesser cytotoxicity, glycine-conjugated and epsilon-NH-Boc-lysine-conjugated DSB, exerted a dose dependent negative effect on VLP assembly and budding. A fifth compound with a low cytotoxicity, EP-39 (ethylene diamine-conjugated DSB), showed a novel type of antiviral effect. EP-39 provoked an aberrant assembly of VLP, resulting in nonenveloped, morula-like particles of 100-nm in diameter. Each morula was composed of nanoparticle subunits of 20-nm in diameter, which possibly mimicked transient intermediates of the HIV-1 Gag assembly process. Chemical cross-linking in situ suggested that EP-39 favored the formation or/and persistence of Pr55Gag trimers over other oligomeric species. EP-39 showed a novel type of negative effect on HIV-1 assembly, targeting the Pr55Gag oligomerisation. The biological effect of EP-39 underlined the critical role of the nature of the side chain at position 28 of BA derivatives in their anti-HIV-1 activity. PMID- 22073299 TI - Altered dark- and photoconversion of phytochrome B mediate extreme light sensitivity and loss of photoreversibility of the phyB-401 mutant. AB - The phyB-401 mutant is 10(3) fold more sensitive to red light than its wild-type analogue and shows loss of photoreversibility of hypocotyl growth inhibition. The phyB-401 photoreceptor displays normal spectral properties and shows almost no dark reversion when expressed in yeast cells. To gain insight into the molecular mechanism underlying this complex phenotype, we generated transgenic lines expressing the mutant and wild-type phyB in phyB-9 background. Analysis of these transgenic lines demonstrated that the mutant photoreceptor displays a reduced rate of dark-reversion but normal P(fr) to P(r) photoconversion in vivo and shows an altered pattern of association/dissociation with nuclear bodies compared to wild-type phyB. In addition we show (i) an enhanced responsiveness to far-red light for hypocotyl growth inhibition and CAB2 expression and (ii) that far-red light mediated photoreversibility of red light induced responses, including inhibition of hypocotyl growth, formation of nuclear bodies and induction of CAB2 expression is reduced in these transgenic lines. We hypothesize that the incomplete photoreversibility of signalling is due to the fact that far-red light induced photoconversion of the chromophore is at least partially uncoupled from the P(fr) to P(r) conformation change of the protein. It follows that the phyB 401 photoreceptor retains a P(fr)-like structure (P(r) (*)) for a few hours after the far-red light treatment. The greatly reduced rate of dark reversion and the formation of a biologically active P(r) (*) conformer satisfactorily explain the complex phenotype of the phyB-401 mutant and suggest that amino acid residues surrounding the position 564 G play an important role in fine-tuning phyB signalling. PMID- 22073300 TI - Shape-induced terminal differentiation of human epidermal stem cells requires p38 and is regulated by histone acetylation. AB - Engineered model substrates are powerful tools for examining interactions between stem cells and their microenvironment. Using this approach, we have previously shown that restricted cell adhesion promotes terminal differentiation of human epidermal stem cells via activation of serum response factor (SRF) and transcription of AP-1 genes. Here we investigate the roles of p38 MAPK and histone acetylation. Inhibition of p38 activity impaired SRF transcriptional activity and shape-induced terminal differentiation of human keratinocytes. In addition, inhibiting p38 reduced histone H3 acetylation at the promoters of SRF target genes, FOS and JUNB. Although histone acetylation correlated with SRF transcriptional activity and target gene expression, treatment with the histone de-acetylase inhibitor, trichostatin A (TSA) blocked terminal differentiation on micro-patterned substrates and in suspension. TSA treatment simultaneously maintained expression of LRIG1, TP63, and ITGB1. Therefore, global histone de acetylation represses stem cell maintenance genes independent of SRF. Our studies establish a novel role for extrinsic physical cues in the regulation of chromatin remodeling, transcription, and differentiation of human epidermal stem cells. PMID- 22073301 TI - Different susceptibility to neurodegeneration of dorsal and ventral hippocampal dentate gyrus: a study with transgenic mice overexpressing GSK3beta. AB - Dorsal hippocampal regions are involved in memory and learning processes, while ventral areas are related to emotional and anxiety processes. Hippocampal dependent memory and behaviour alterations do not always come out in neurodegenerative diseases at the same time. In this study we have tested the hypothesis that dorsal and ventral dentate gyrus (DG) regions respond in a different manner to increased glycogen synthase kinase-3beta (GSK3beta) levels in GSK3beta transgenic mice, a genetic model of neurodegeneration. Reactive astrocytosis indicate tissue stress in dorsal DG, while ventral area does not show that marker. These changes occurred with a significant reduction of total cell number and with a significantly higher level of cell death in dorsal area than in ventral one as measured by fractin-positive cells. Biochemistry analysis showed higher levels of phosphorylated GSK3beta in those residues that inactivate the enzyme in hippocampal ventral areas compared with dorsal area suggesting that the observed susceptibility is in part due to different GSK3 regulation. Previous studies carried out with this animal model had demonstrated impairment in Morris Water Maze and Object recognition tests point out to dorsal hippocampal atrophy. Here, we show that two tests used to evaluate emotional status, the light-dark box and the novelty suppressed feeding test, suggest that GSK3beta mice do not show any anxiety-related disorder. Thus, our results demonstrate that in vivo overexpression of GSK3beta results in dorsal but not ventral hippocampal DG neurodegeneration and suggest that both areas do not behave in a similar manner in neurodegenerative processes. PMID- 22073302 TI - Thermal imaging of the periorbital regions during the presentation of an auditory startle stimulus. AB - Infrared thermal imaging of the inner canthi of the periorbital regions of the face can potentially serve as an input signal modality for an alternative access system for individuals with conditions that preclude speech or voluntary movement, such as total locked-in syndrome. However, it is unknown if the temperature of these regions is affected by the human startle response, as changes in the facial temperature of the periorbital regions manifested during the startle response could generate false positives in a thermography-based access system. This study presents an examination of the temperature characteristics of the periorbital regions of 11 able-bodied adult participants before and after a 102 dB auditory startle stimulus. The results indicate that the startle response has no substantial effect on the mean temperature of the periorbital regions. This indicates that thermography-based access solutions would be insensitive to startle reactions in their user, an important advantage over other modalities being considered in the context of access solutions for individuals with a severe motor disability. PMID- 22073303 TI - Do food web models reproduce the structure of mutualistic networks? AB - BACKGROUND: Simple models inspired by processes shaping consumer-resource interactions have helped to establish the primary processes underlying the organization of food webs, networks of trophic interactions among species. Because other ecological interactions such as mutualisms between plants and their pollinators and seed dispersers are inherently based in consumer-resource relationships we hypothesize that processes shaping food webs should organize mutualistic relationships as well. METHODOLOGY/PRINCIPAL FINDINGS: We used a likelihood-based model selection approach to compare the performance of food web models and that of a model designed for mutualisms, in reproducing the structure of networks depicting mutualistic relationships. Our results show that these food web models are able to reproduce the structure of most of the mutualistic networks and even the simplest among the food web models, the cascade model, often reproduce overall structural properties of real mutualistic networks. CONCLUSIONS/SIGNIFICANCE: Based on our results we hypothesize that processes leading to feeding hierarchy, which is a characteristic shared by all food web models, might be a fundamental aspect in the assembly of mutualisms. These findings suggest that similar underlying ecological processes might be important in organizing different types of interactions. PMID- 22073304 TI - CXCR4 antagonist AMD3100 modulates claudin expression and intestinal barrier function in experimental colitis. AB - Ulcerative colitis is a gastrointestinal disorder characterized by local inflammation and impaired epithelial barrier. Previous studies demonstrated that CXC chemokine receptor 4 (CXCR4) antagonists could reduce colonic inflammation and mucosal damage in dextran sulfate sodium (DSS)-induced colitis. Whether CXCR4 antagonist has action on intestinal barrier and the possible mechanism, is largely undefined. In the present study, the experimental colitis was induced by administration of 5% DSS for 7 days, and CXCR4 antagonist AMD3100 was administered intraperitoneally once daily during the study period. For in vitro study, HT-29/B6 colonic cells were treated with cytokines or AMD3100 for 24 h until assay. DSS-induced colitis was characterized by morphologic changes in mice. In AMD3100-treated mice, epithelial destruction, inflammatory infiltration, and submucosal edema were markedly reduced, and the disease activity index was also significantly decreased. Increased intestinal permeability in DSS-induced colitis was also significantly reduced by AMD3100. The expressions of colonic claudin-1, claudin-3, claudin-5, claudin-7 and claudin-8 were markedly decreased after DSS administration, whereas colonic claudin-2 expression was significantly decreased. Treatment with AMD3100 prevented all these changes. However, AMD3100 had no influence on claudin-3, claudin-5, claudin-7 and claudin-8 expression in HT-29/B6 cells. Cytokines as TNF-alpha, IL-6, and IFN-gamma increased apoptosis and monolayer permeability, inhibited the wound-healing and the claudin-3, claudin-7 and claudin-8 expression in HT-29/B6 cells. We suggest that AMD3100 acted on colonic claudin expression and intestinal barrier function, at least partly, in a cytokine-dependent pathway. PMID- 22073305 TI - LIS1 regulates osteoclast formation and function through its interactions with dynein/dynactin and Plekhm1. AB - Microtubule organization and lysosomal secretion are both critical for the activation and function of osteoclasts, highly specialized polykaryons that are responsible for bone resorption and skeletal homeostasis. Here, we have identified a novel interaction between microtubule regulator LIS1 and Plekhm1, a lysosome-associated protein implicated in osteoclast secretion. Decreasing LIS1 expression by shRNA dramatically attenuated osteoclast formation and function, as shown by a decreased number of mature osteoclasts differentiated from bone marrow macrophages, diminished resorption pits formation, and reduced level of CTx-I, a bone resorption marker. The ablated osteoclast formation in LIS1-depleted macrophages was associated with a significant decrease in macrophage proliferation, osteoclast survival and differentiation, which were caused by reduced activation of ERK and AKT by M-CSF, prolonged RANKL-induced JNK activation and declined expression of NFAT-c1, a master transcription factor of osteoclast differentiation. Consistent with its critical role in microtubule organization and dynein function in other cell types, we found that LIS1 binds to and colocalizes with dynein in osteoclasts. Loss of LIS1 led to disorganized microtubules and aberrant dynein function. More importantly, the depletion of LIS1 in osteoclasts inhibited the secretion of Cathepsin K, a crucial lysosomal hydrolase for bone degradation, and reduced the motility of osteoclast precursors. These results indicate that LIS1 is a previously unrecognized regulator of osteoclast formation, microtubule organization, and lysosomal secretion by virtue of its ability to modulate dynein function and Plekhm1. PMID- 22073306 TI - Protein replacement therapy partially corrects the cholesterol-storage phenotype in a mouse model of Niemann-Pick type C2 disease. AB - Niemann-Pick type C2 (NPC2) disease is a fatal autosomal recessive neurovisceral degenerative disorder characterized by late endosomal-lysosomal sequestration of low-density lipoprotein derived cholesterol. The breach in intracellular cholesterol homeostasis is caused by deficiency of functional NPC2, a soluble sterol binding protein targeted to the lysosomes by binding the mannose-6 phosphate receptor. As currently there is no effective treatment for the disorder, we have investigated the efficacy of NPC2 replacement therapy in a murine gene-trap model of NPC2-disease generated on the 129P2/OlaHsd genetic background. NPC2 was purified from bovine milk and its functional competence assured in NPC2-deficient fibroblasts using the specific cholesterol fluorescent probe filipin. For evaluation of phenotype correction in vivo, three-week-old NPC2(-/-) mice received two weekly intravenous injections of 5 mg/kg NPC2 until trial termination 66 days later. Whereas the saline treated NPC2(-/-) mice exhibited massive visceral cholesterol storage as compared to their wild-type littermates, administration of NPC2 caused a marked reduction in cholesterol build up. The histological findings, indicating an amelioration of the disease pathology in liver, spleen, and lungs, corroborated the biochemical results. Little or no difference in the overall cholesterol levels was observed in the kidneys, blood, cerebral cortex and hippocampus when comparing NPC2(-/-) and wild type mice. However, cerebellum cholesterol was increased about two fold in NPC2( /-) mice compared with wild-type littermates. Weight gain performance was slightly improved as a result of the NPC2 treatment but significant motor coordination deficits were still observed. Accordingly, ultrastructural cerebellar abnormalities were detected in both saline treated and NPC2 treated NPC2(-/-) animals 87 days post partum. Our data indicate that protein replacement may be a beneficial therapeutic approach in the treatment of the visceral manifestations in NPC2 disease and further suggest that neurodegeneration is not secondary to visceral dysfunction. PMID- 22073307 TI - Attentional demands of movement observation as tested by a dual task approach. AB - Movement observation (MO) has been shown to activate the motor cortex of the observer as indicated by an increase of corticomotor excitability for muscles involved in the observed actions. Moreover, behavioral work has strongly suggested that this process occurs in a near-automatic manner. Here we further tested this proposal by applying transcranial magnetic stimulation (TMS) when subjects observed how an actor lifted objects of different weights as a single or a dual task. The secondary task was either an auditory discrimination task (experiment 1) or a visual discrimination task (experiment 2). In experiment 1, we found that corticomotor excitability reflected the force requirements indicated in the observed movies (i.e. higher responses when the actor had to apply higher forces). Interestingly, this effect was found irrespective of whether MO was performed as a single or a dual task. By contrast, no such systematic modulations of corticomotor excitability were observed in experiment 2 when visual distracters were present. We conclude that interference effects might arise when MO is performed while competing visual stimuli are present. However, when a secondary task is situated in a different modality, neural responses are in line with the notion that the observers motor system responds in a near automatic manner. This suggests that MO is a task with very low cognitive demands which might be a valuable supplement for rehabilitation training, particularly, in the acute phase after the incident or in patients suffering from attention deficits. However, it is important to keep in mind that visual distracters might interfere with the neural response in M1. PMID- 22073308 TI - beta-AR blockers suppresses ER stress in cardiac hypertrophy and heart failure. AB - BACKGROUND: Long-term beta-adrenergic receptor (beta-AR) blockade reduces mortality in patients with heart failure. Chronic sympathetic hyperactivity in heart failure causes sustained beta-AR activation, and this can deplete Ca(2+) in endoplasmic reticulum (ER) leading to ER stress and subsequent apoptosis. We tested the effect of beta-AR blockers on ER stress pathway in experimental model of heart failure. METHODS AND DISCUSSIONS: ER chaperones were markedly increased in failing hearts of patients with end-stage heart failure. In Sprague-Dawley rats, cardiac hypertrophy and heart failure was induced by abdominal aortic constriction or isoproterenol subcutaneous injection. Oral beta-AR blockers treatment was performed in therapy groups. Cardiac remodeling and left ventricular function were analyzed in rats failing hearts. After 4 or 8 weeks of banding, rats developed cardiac hypertrophy and failure. Cardiac expression of ER chaperones was significantly increased. Similar to the findings above, sustained isoproterenol infusion for 2 weeks induced cardiac hypertrophy and failure with increased ER chaperones and apoptosis in hearts. beta-AR blockers treatment markedly attenuated these pathological changes and reduced ER stress and apoptosis in failing hearts. On the other hand, beta-AR agonist isoproterenol induced ER stress and apoptosis in cultured cardiomyocytes. beta-AR blockers largely prevented ER stress and protected myocytes against apoptosis. And beta-AR blockade significantly suppressed the overactivation of CaMKII in isoproterenol stimulated cardiomyocytes and failing hearts in rats. CONCLUSIONS: Our results demonstrated that ER stress occurred in failing hearts and this could be reversed by beta-AR blockade. Alleviation of ER stress may be an important mechanism underlying the therapeutic effect of beta-AR blockers on heart failure. PMID- 22073309 TI - Visfatin impairs endothelium-dependent relaxation in rat and human mesenteric microvessels through nicotinamide phosphoribosyltransferase activity. AB - Visfatin, also known as extracellular pre-B-cell colony-enhancing factor (PBEF) and nicotinamide phosphoribosyltransferase (Nampt), is an adipocytokine whose circulating levels are enhanced in metabolic disorders, such as type 2 diabetes mellitus and obesity. Circulating visfatin levels have been positively associated with vascular damage and endothelial dysfunction. Here, we investigated the ability of visfatin to directly impair vascular reactivity in mesenteric microvessels from both male Sprague-Dawley rats and patients undergoing non urgent, non-septic abdominal surgery. The pre-incubation of rat microvessels with visfatin (50 and 100 ng/mL) did not modify the contractile response to noradrenaline (1 pmol/L to 30 umol/L), as determined using a small vessel myograph. However, visfatin (10 to 100 ng/mL) concentration-dependently impaired the relaxation to acetylcholine (ACh; 100 pmol/L to 3 umol/L), without interfering with the endothelium-independent relaxation to sodium nitroprusside (1 nmol/L to 3 umol/L). In both cultured human umbilical vein endothelial cells and rat microvascular preparations, visfatin (50 ng/mL) stimulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, as determined by lucigenin-derived chemiluminiscence. The relaxation to ACh impaired by visfatin was restored by the NADPH oxidase inhibitor apocynin (10 umol/L). Additionally, the Nampt inhibitor APO866 (10 mmol/L to 10 umol/L), but not an insulin receptor blocking antibody, also prevented the stimulation of NADPH oxidase and the relaxation impairment elicited by visfatin. Accordingly, the product of Nampt activity nicotinamide mononucleotide (100 nmol/L to 1 mmol/L) stimulated endothelial NADPH oxidase activity and concentration-dependently impaired ACh induced vasorelaxation. In human mesenteric microvessels pre-contracted with 35 mmol/L potassium chloride, the endothelium-dependent vasodilation to bradykinin (1 nmol/L to 3 umol/L) was equally impaired by visfatin and restored upon co incubation with APO866. In conclusion, visfatin impairs endothelium-dependent relaxation through a mechanism involving NADPH oxidase stimulation and relying on Nampt enzymatic activity, and therefore arises as a potential new player in the development of endothelial dysfunction. PMID- 22073310 TI - Association of genetic loci with blood lipids in the Chinese population. AB - BACKGROUND: Recent genome-wide association (GWA) studies have identified a number of novel genetic determinants of blood lipid concentrations in Europeans. However, it is still unclear whether these loci identified in the Caucasian GWA studies also exert the same effect on lipid concentrations in the Chinese population. METHODS AND RESULTS: We conducted a replication study assessing associations between SNPs at 15 loci and blood lipid and lipoprotein concentrations in two Chinese cohorts, comprising 2533 and 2105 individuals respectively. SNPs in APO(A1/C3/A4/A5), TIMD4-HAVCR1, DOCK7, TRIB1, ABCA1, and TOMM40-APOE showed strong associations with at least one lipids trait, and rs174546 in FADS1/2/3 showed modest association with triglyceride in the Chinese population. CONCLUSIONS: We successfully replicated 7 loci associated plasma lipid concentrations in the Chinese population. Our study confirmed the implication of APO(A1/C3/A4/A5), TOMM40-APOE, ABCA1, DOCK7, TIMD4-HAVCR1, TRIB1 and FADS1/2 in plasma lipid and lipoprotein concentrations in Chinese population. PMID- 22073311 TI - The roles of dimensionality, canopies and complexity in ecosystem monitoring. AB - Canopies are common among autotrophs, increasing their access to light and thereby increasing competitive abilities. If viewed from above canopies may conceal objects beneath them creating a 'canopy effect'. Due to complexities in collecting 3-dimensional data, most ecosystem monitoring programmes reduce dimensionality when sampling, resorting to planar views. The resultant 'canopy effects' may bias data interpretation, particularly following disturbances. Canopy effects are especially relevant on coral reefs where coral cover is often used to evaluate and communicate ecosystem health. We show that canopies hide benthic components including massive corals and algal turfs, and as planar views are almost ubiquitously used to monitor disturbances, the loss of vulnerable canopy-forming corals may bias findings by presenting pre-existing benthic components as an altered system. Our reliance on planar views in monitoring ecosystems, especially coral cover on reefs, needs to be reassessed if we are to better understand the ecological consequences of ever more frequent disturbances. PMID- 22073312 TI - A switch from canonical to noncanonical Wnt signaling mediates drug resistance in colon cancer cells. AB - Butyrate, a fermentation product of fiber in the colon, acts as a histone deacetylase inhibitor (HDACi) and induces apoptosis in colon cancer (CC) cells in vitro. We have reported that the apoptotic effects of butyrate are dependent upon the hyperactivation of the Wnt/beta-catenin pathway. However, prolonged exposure of CC cells to increasing concentrations of butyrate results in the acquisition of resistance to the Wnt/beta-catenin- and apoptosis-inducing effects of this agent, as well as cross-resistance to structurally different HDACis. Here we report that one mechanism whereby HDACi resistance arises is through the increase of beta-catenin-independent (noncanonical) Wnt signaling. Compared to HDACi sensitive HCT-116 CC cells, HDACi-resistant HCT-R cells exhibit higher levels of AKT/PKB cell survival signaling, which is in part induced by WNT5A and its receptor ROR2. The induction of AKT signaling by HDACis is also detected in other CC cell lines, albeit to a lesser extent than in the drug-resistant HCT-R cells. The observations suggested that the apoptotic effect of butyrate and other HDACis in CC cells can be augmented by inhibitors of pAKT. In agreement with the hypothesis, the combination of MK2206, a pAKT inhibitor, and a HDACi (butyrate or LBH589) induced higher apoptosis in CC cells compared to each agent alone. The exposure to both agents also re-sensitized the HCT-R cells to apoptosis. Finally, the concept of simultaneously inducing canonical Wnt activity and suppressing AKT signaling was translated into a combination of diet-derived agents. Diet-derived pAKT inhibitors (caffeic acid phethyl ester, sulforaphane, dilallyl trisulfide) suppressed the butyrate-induced levels of pAKT, and increased the apoptotic effects of butyrate in both drug-sensitive and drug-resistant CC cells.Our findings can be translated into (a) CC therapy employing combinations of synthetic HDACis and inhibitors of pAKT, as well as (b) CC prevention based upon diets that result in sufficient amounts of butyrate and pAKT inhibitors. PMID- 22073313 TI - RpkA, a highly conserved GPCR with a lipid kinase domain, has a role in phagocytosis and anti-bacterial defense. AB - RpkA (Receptor phosphatidylinositol kinase A) is an unusual seven-helix transmembrane protein of Dictyostelium discoideum with a G protein coupled receptor (GPCR) signature and a C-terminal lipid kinase domain (GPCR-PIPK) predicted as a phosphatidylinositol-4-phosphate 5-kinase. RpkA-homologs are present in all so far sequenced Dictyostelidae as well as in several other lower eukaryotes like the oomycete Phytophthora, and in the Legionella host Acanthamoeba castellani. Here we show by immunofluorescence that RpkA localizes to endosomal membranes and is specifically recruited to phagosomes. RpkA interacts with the phagosomal protein complex V-ATPase as proteins of this complex co-precipitate with RpkA-GFP as well as with the GST-tagged PIPK domain of RpkA. Loss of RpkA leads to a defect in phagocytosis as measured by yeast particle uptake. The uptake of the pathogenic bacterium Legionella pneumophila was however unaltered whereas its intra-cellular replication was significantly enhanced in rpkA(-). The difference between wild type and rpkA(-) was even more prominent when L. hackeliae was used. When we investigated the reason for the enhanced susceptibility for L. pneumophila of rpkA(-) we could not detect a difference in endosomal pH but rpkA(-) showed depletion of phosphoinositides (PIP and PIP(2)) when we compared metabolically labeled phosphoinositides from wild type and rpkA(-). Furthermore rpkA(-) exhibited reduced nitrogen starvation tolerance, an indicator for a reduced autophagy rate. Our results indicate that RpkA is a component of the defense system of D. discoideum as well as other lower eukaryotes. PMID- 22073314 TI - Sweepoviruses cause disease in sweet potato and related Ipomoea spp.: fulfilling Koch's postulates for a divergent group in the genus begomovirus. AB - Sweet potato (Ipomoea batatas) and related Ipomoea species are frequently infected by monopartite begomoviruses (genus Begomovirus, family Geminiviridae), known as sweepoviruses. Unlike other geminiviruses, the genomes of sweepoviruses have been recalcitrant to rendering infectious clones to date. Thus, Koch's postulates have not been fullfilled for any of the viruses in this group. Three novel species of sweepoviruses have recently been described in Spain: Sweet potato leaf curl Lanzarote virus (SPLCLaV), Sweet potato leaf curl Spain virus (SPLCSV) and Sweet potato leaf curl Canary virus (SPLCCaV). Here we describe the generation of the first infectious clone of an isolate (ES:MAL:BG30:06) of SPLCLaV. The clone consisted of a complete tandem dimeric viral genome in a binary vector. Successful infection by agroinoculation of several species of Ipomoea (including sweet potato) and Nicotiana benthamiana was confirmed by PCR, dot blot and Southern blot hybridization. Symptoms observed in infected plants consisted of leaf curl, yellowing, growth reduction and vein yellowing. Two varieties of sweet potato, 'Beauregard' and 'Promesa', were infected by agroinoculation, and symptoms of leaf curl and interveinal loss of purple colouration were observed, respectively. The virus present in agroinfected plants was readily transmitted by the whitefly Bemisia tabaci to I. setosa plants. The progeny virus population present in agroinfected I. setosa and sweet potato plants was isolated and identity to the original isolate was confirmed by sequencing. Therefore, Koch's postulates were fulfilled for the first time for a sweepovirus. PMID- 22073315 TI - KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy. AB - BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART) have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR) and their ligands class I human leukocyte antigen (HLA), could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+) T-cell count <200/mm(3)) and full responders (FR, N = 104, CD4(+) T-cell count >350/mm(3)). Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005). The functional compound genotype HLA C1(+)/KIR2DL3(+), even at multivariable analysis, when adjusted for nadir CD4(+) T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals) 0.34 (0.13-0.88), P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy. PMID- 22073316 TI - Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression. AB - Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells. PMID- 22073317 TI - Microevolution of cis-regulatory elements: an example from the pair-rule segmentation gene fushi tarazu in the Drosophila melanogaster subgroup. AB - The importance of non-coding DNAs that control transcription is ever noticeable, but the characterization and analysis of the evolution of such DNAs presents challenges not found in the analysis of coding sequences. In this study of the cis-regulatory elements of the pair rule segmentation gene fushi tarazu (ftz) I report the DNA sequences of ftz's zebra element (promoter) and a region containing the proximal enhancer from a total of 45 fly lines belonging to several populations of the species Drosophila melanogaster, D. simulans, D. sechellia, D. mauritiana, D. yakuba, D. teissieri, D. orena and D. erecta. Both elements evolve at slower rate than ftz synonymous sites, thus reflecting their functional importance. The promoter evolves more slowly than the average for ftz's coding sequence while, on average, the enhancer evolves more rapidly, suggesting more functional constraint and effective purifying selection on the former. Comparative analysis of the number and nature of base substitutions failed to detect significant evidence for positive/adaptive selection in transcription-factor-binding sites. These seem to evolve at similar rates to regions not known to bind transcription factors. Although this result reflects the evolutionary flexibility of the transcription factor binding sites, it also suggests a complex and still not completely understood nature of even the characterized cis-regulatory sequences. The latter seem to contain more functional parts than those currently identified, some of which probably transcription factor binding. This study illustrates ways in which functional assignments of sequences within cis-acting sequences can be used in the search for adaptive evolution, but also highlights difficulties in how such functional assignment and analysis can be carried out. PMID- 22073318 TI - Differential susceptibility to fathers' care and involvement: The moderating effect of infant reactivity. AB - The differential susceptibility hypothesis suggests that children differ in their susceptibility to the influence of both positive and negative environmental factors. Children with reactive temperaments are hypothesised to be particularly susceptible to environmental influences, both for better and for worse. The present study sought to investigate whether infant temperament moderates the influence of fathers on child prosocial and problem behaviours. In a large prospective population study (Avon Longitudinal Study of Parents and Children), 5064 children were followed between the ages of six and 81 months (63/4 years). Infant temperament, child behaviours, and fathers' involvement and depression were assessed.Although no overall moderating effect of reactive temperament was found for father involvement or depression, there was an interaction between reactivity, child gender, and father involvement. Girls with reactive temperaments were more susceptible to father involvement, showing significantly fewer problem behaviours and more prosocial behaviours when fathers were more involved, and more problem behaviours and fewer prosocial behaviours with less father involvement. The findings provide some support for the differential susceptibility hypothesis and extend existing findings to include effects of fathers' involvement on positive and negative behavioural outcomes. PMID- 22073319 TI - Future applications of contrast ultrasound. AB - Contrast agents are currently used during echocardiography for enhancement of structure and function, as well as for perfusion imaging. The next frontiers in contrast ultrasonography are targeted imaging, and using microbubbles for therapeutic purposes. Targeted imaging is the detection of specific components of cardiovascular disease in vivo, with microbubbles which may non-specifically attach to diseased endothelial cells, or with microbubbles which have been specifically designed to detect a pathologic process. Therapeutic applications of contrast ultrasonography include the use of microbubbles to enhance delivery of agents (like drugs, genes, growth factors, etc.) to the endothelium or perivascular cells. This review will discuss differences in contrast agents used for current applications versus targeted imaging, technical considerations required to achieve site-specific imaging, and potential applications of this technology. The potential for contrast ultrasonography to enhance drug and gene delivery to tissue will also be discussed. PMID- 22073320 TI - Assessment of right ventricular structure and function in pulmonary hypertension. AB - Right ventricular function plays an important role in determining cardiac symptoms and exercise capacity in chronic heart failure. It is known that right ventricle has complex anatomy and physiology. The purpose of this review paper is to demonstrate the best assessment of the right ventricle with current echocardiography. Echocardiography can assess sufficiently right ventricular structure and function and also suggest prognosis in pulmonary hypertension patients, especially with the use of modern imaging techniques. Finally, the new imaging modality of real time three dimensional echocardiography is interchangeable to cardiac magnetic resonance in reproducibility and accuracy. PMID- 22073321 TI - Aortic root volume and geometry: ready for clinical application? PMID- 22073322 TI - Validation of three-dimensional echocardiography for quantification of aortic root geometry: comparison with multi-detector computed tomography. AB - BACKGROUND: Three-dimensional (3D) echocardiography has been reported to be valuable for evaluating the geometry of cardiac chambers. We validated the accuracy of 3D transthoracic echocardiography for quantifying aortic root geometry in comparison with cardiac multi-detector computed tomography (MDCT). METHODS: Twenty-three patients who underwent cardiac MDCT and showed normal left ventricular ejection fraction (> 55%), as assessed by 2-dimensional transthoracic echocardiography, were enrolled (12 male, mean 53 +/- 9 years). We defined the aortic root volume as the volume from the aortic annulus to the sinotubular junction. The aortic root volume at end-diastole measured by both cardiac MDCT and 3D echocardiography was assessed. RESULTS: The cross-sectional area of the aortic root was asymmetric. At the annulus level, the cross-sectional area showed asymmetric triangle. From the aortic annulus to the most dilated point of the sinus of Valsalva, the asymmetric triangular shape was maintained. From the most dilated point of the sinus of Valsalva to the sinotubular junction, the cross sectional shape of the aortic root changed to oval. The average aortic root volumes measured by 3D echocardiography (ARV-3DE) were 13.6 +/- 4.8 mL at end diastole and 14.1 +/- 5.3 mL at end-systole, respectively. The average aortic root volume measured by MDCT at end-diastole (ARV-CT) was 14.1 +/- 5.7 mL. At end diastole, the ARV-3DE correlated well with the ARV-CT (R(2) = 0.926, difference = 0.5 +/- 1.7 mL), and the two methods were in excellent agreement (the percent difference was 0%). CONCLUSION: Our results demonstrate both the feasibility and accuracy of 3D echocardiography for the clinical assessment of the geometry of the aortic root. PMID- 22073324 TI - Complete Atrioventricular Block due to Infective Endocarditis of Bicuspid Aortic Valve. AB - A 38-year-old man visited our emergency department presenting with a 6-day persistent fever. The man had undergone an orthodontic procedure 7 days prior to the visit. He had a fever with a temperature of 38.2C and a diastolic murmur (grade III) was detected at the left sternal border. Reddish-brown lines beneath the nails were present, and raised lesions which were red and painful were detected on the soles of the patient's feet. Laboratory findings showed an elevated inflammatory marker. Transthoracic and transesophageal echocardiograms, showed a bicuspid aortic valve, and moderate aortic regurgitation and vegetation were noted. Treatment with antibiotics was given, but 4 days later, a 12 lead electrocardiogram revealed complete atrioventricular (AV) block. Immediately, a temporary pacemaker was inserted, and the following day an aortic valve replacement was performed. Intraoperative findings revealed a fistula around the AV node. He has suffered no subsequent cardiac events during the follow-up. PMID- 22073323 TI - Subclinical Myocardial Dysfunction in Metabolic Syndrome Patients without Hypertension. AB - BACKGROUND: The aim of this study was to evaluate myocardial function in patients with non-hypertensive metabolic syndrome. METHODS: We selected metabolic syndrome patients (n = 42) without evidence of hypertension and compared them to age matched control individuals (n = 20). All patients were evaluated by two dimensional and tissue Doppler echocardiography including tissue Doppler derived strain and strain rate measurements. RESULTS: There were no significant differences between the two groups in mitral E and A inflow velocities or the E/A ratio. However, systolic and early diastolic myocardial velocities, and strain rate were significantly lower in patients with metabolic syndrome than in the control group (all p < 0.05). Multiple stepwise regression analyses revealed that age, waist circumference, and systolic blood pressure were independently associated with peak systolic myocardial velocity. CONCLUSION: These results indicate that metabolic syndrome patients without hypertension may have decrease of myocardial systolic and early diastolic velocities on tissue Doppler imaging, even if they appear to have normal systolic and diastolic function on conventional echocardiography. PMID- 22073325 TI - Hypertensive heart failure associated with middle aortic syndrome reversed dramatically by endovascular management. AB - A 42-year-old male patient presented with refractory hypertension and congestive heart failure. He had taken hydrochlorthiazide 50 mg, carvedilol 25 mg, diltiazem 180 mg, and losartan 100 mg per day. Aortogram revealed a severe luminal narrowing in the distal thoracic aorta with a peak systolic pressure gradient of 60 mmHg across the lesion. Endovascular management was performed with 22 * 80 mm self-expandable Nitinol-S stent after predilation with 10 * 40 mm balloon. After endovascular management, the patient's blood pressure, left ventricular ejection fraction (LVEF) and dilated LV dimension were remarkably improved. PMID- 22073326 TI - Spontaneously healed membranous type ventricular septal defect with malaligned interventricular septal wall and double-chambered right ventricle in a 56-year old patient. AB - A 56-year-old male presented with resting dyspnea and chest discomfort for several years. During transthoracic and transesophageal echocardiography, a spontaneously healed membranous type ventricular septal defect (VSD) with malaligned interventricular septal wall, aneurysmal changes, a subaortic ridge and a double-chambered right ventricle (DCRV) was observed. When combined with DCRV, VSD with malalignment between the outlet and trabecular septa was associated with tetralogy of Fallot. The subaortic ridge was due to turbulent flow caused by the malalignment-type VSD. The VSD with malaligned interventricular septal wall can be developed after aneurismal changes of a perimembranous VSD. We report here in the unusual case of a 56-year-old patient who had a pathology complex comprising DCRV, subaortic ridge, spontaneously healed membranous type VSD with malaligned interventricular septal wall, and survived with surgical treatment. PMID- 22073327 TI - Left ventricular thrombus associated with takotsubo cardiomyopathy: a cardioembolic cause of cerebral infarction. AB - Takotsubo cardiomyopathy, also called stress-induced cardiomyopathy, usually occurs in patients with severe emotional or physiologic stress. The prognosis is favorable, and the wall motion abnormlities normalize within weeks. However, stress-induced cardiomyopathy is rarely assosicated with left ventricular thrombus and thromboembolic complications. Here, we report a case of stress induced cardiomyopathy with left ventricular thrombus that embolized to cause cerebral infarction. PMID- 22073328 TI - Prominent crista terminalis in patients with embolic events. AB - A prominent crista terminalis is a normal anatomic variant which consist of thick muscular bridge within the right atrium. However, it could be often misdiagnosed with an abnormal mass on the transthoracic echocardiography. The case report presented here, describe the findings of transthoracic echocardiography that suggested a right atrial mass in patients with pulmonary embolism. However, subsequent transesophageal echocardiography and cardiac computed tomography/magnetic resonance imaging differentiated a true right atrial mass from a prominent crista terminalis. PMID- 22073329 TI - Transient use of oral bosentan can be an additional option to reduce pulmonary arterial hypertension in a patient with severe pulmonary arterial hypertension associated with atrial septal defect. AB - Atrial septal defect (ASD) with severe pulmonary arterial hypertension (PAH) is thought to preclude shunt closure. However, there are several reports that vasodilator treatment is associated with good clinical outcome in these patients, recently. We report a case of good clinical outcome in a patient with ASD and severe PAH successfully treated with operative closure of ASD and subsequent use of oral bosentan medication. This case supports that the corrective repair of ASD and an oral bosentan treatment can be one of the treatment options in the selected patients with severe PAH associated with ASD. PMID- 22073330 TI - A case of balanced type double aortic arch diagnosed incidentally by transthoracic echocardiography in an asymptomatic adult patient. AB - A 36-year-old male patient with no remarkable medical history was admitted to our hospital for a health check up. On chest radiography, bilateral aortic notches at the level of aortic arch were shown suggesting aortic arch anomaly without any clinical symptoms. Two aortic arches were almost same-in-size on suprasternal view of transthoracic echocardiography. In addition, multidetector computed tomography showed balanced type double aortic arch forming a complete vascular ring which encircled the trachea and esophagus. The trachea was slightly compressed by the vascular ring whereas the esophagus was intact. Nevertheless, the pulmonary function test was normal. The patient was discharged from hospital with instructions for periodic follow-up. PMID- 22073331 TI - Ball-shaped thrombi in the left ventricular apex. PMID- 22073332 TI - Erratum: retained subintimal pellet in a carotid artery. AB - [This corrects the article on p. 105 in vol. 19, PMID: 21860728.]. PMID- 22073355 TI - Histomorphometric characteristics of immune cells in small intestine of pigs perorally immunized with vaccine candidate F18ac nonenterotoxigenic E. coli strain. AB - Colidiarrhea and colienterotoxemia caused by F4(+) and/or F18(+) enterotoxigenic E. coli (ETEC) strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac(+) non-ETEC vaccine candidate strain against challenge infection with F4ac(+) ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs.We also evaluated levamisole as an immune response modifier (IRM) and its adjuvanticity when given in the combination with the experimental vaccine. The pigs were parenterally immunized with either levamisole (at days -2, -1 and 0) or with levamisole and perorally given F18ac(+) non-ETEC strain (at day 0), and challenged with F4ac(+) ETEC strain 7 days later.At day 13 the pigs were euthanatized and sampled for immunohistological/histomorphometrical analyses. Lymphoid CD3(+), CD45RA(+), CD45RC(+), CD21(+), IgA(+) and myeloid SWC3(+) cell subsets were identified in jejunal and ileal epithelium, lamina propria and Peyer's patches using the avidin biotin complex method, and their numbers were determined by computer-assisted histomorphometry. Quantitative immunophenotypic analyses showed that levamisole treated pigs had highly increased numbers of jejunal CD3(+), CD45RC(+) and SWC3(+) cells (p<0.05) as compared to those recorded in nontreated control pigs.In the ileum of these pigs we have recorded that only CD21(+) cells were significantly increased (p<0.01). The pigs that were treated with levamisole adjuvanted experimental vaccine had significantly increased numbers of all tested cell subsets in both segments of the small intestine. It was concluded that levamisole adjuvanted F18ac(+) non-ETEC vaccine was a requirement for the elicitation of protective gut immunity in this model; nonspecific immunization with levamisole was less effective, but confirmed its potential as an IRM. PMID- 22073356 TI - Localization of DNA methyltransferase-1 during oocyte differentiation, in vitro maturation and early embryonic development in cow. AB - DNA methyltransferase-1 (Dnmt1) is involved in the maintenance of DNA methylation patterns and is crucial for normal mammalian development. The aim of the present study was to assess the localization of Dnmt1 in cow, during the latest phases of oocyte differentiation and during the early stages of segmentation. Dnmt1 expression and localization were assessed in oocytes according to the chromatin configuration, which in turn provides an important epigenetic mechanism for the control of global gene expression and represents a morphological marker of oocyte differentiation. We found that the initial chromatin condensation was accompanied by a slight increase in the level of global DNA methylation, as assessed by 5 methyl-cytosine immunostaining followed by laser scanning confocal microscopy analysis (LSCM). RT-PCR confirmed the presence of Dnmt1 transcripts throughout this phase of oocyte differentiation. Analogously, Dnmt1 immunodetection and LSCM indicated that the protein was always present and localized in the cytoplasm, regardless the chromatin configuration and the level of global DNA methylation. Moreover, our data indicate that while Dnmt1 is retained in the cytoplasm in metaphase II stage oocytes and zygotes, it enters the nuclei of 8-16 cell stage embryos. As suggested in mouse, the functional meaning of the presence of Dnmt1 in the bovine embryo nuclei could be the maintainement of the methylation pattern of imprinted genes. In conclusion, the present work provides useful elements for the study of Dnmt1 function during the late stage of oocyte differentiation, maturation and early embryonic development in mammals. PMID- 22073357 TI - p53 and telomerase control rat myocardial tissue response to hypoxia and ageing. AB - Cellular senescence implies loss of proliferative and tissue regenerative capability. Also hypoxia, producing Reactive Oxygen Species (ROS), can damage cellular components through the oxidation of DNA, proteins and lipids, thus influencing the shortening of telomeres.Since ribonucleoprotein Telomerase (TERT), catalyzing the replication of the ends of eukaryotic chromosomes, promotes cardiac muscle cell proliferation, hypertrophy and survival, here we investigated its role in the events regulating apoptosis occurrence and life span in hearts deriving from young and old rats exposed to hypoxia.TUNEL (terminal deoxinucleotidyl -transferase- mediated dUTP nick end-labeling) analysis reveals an increased apoptotic cell number in both samples after hypoxia exposure, mainly in the young with respect to the old. TERT expression lowers either in the hypoxic young, either in the old in both experimental conditions, with respect to the normoxic young. These events are paralleled by p53 and HIF-1 alpha expression dramatic increase and by p53/ HIF-1 alpha co-immunoprecipitation in the hypoxic young, evidencing the young subject as the most stressed by such challenge. These effects could be explained by induction of damage to genomic DNA by ROS that accelerates cell senescence through p53 activation. Moreover, by preventing TERT enzyme down-regulation, cell cycle exit and apoptosis occurrence could be delayed and new possibilities for intervention against cell ageing and hypoxia could be opened. PMID- 22073358 TI - TRPC1 expression and distribution in rat hearts. AB - Transient receptor potential canonical (TRPC) proteins have been identified as a family of plasma membrane calcium-permeable channels. TRPC proteins can be activated by various stimuli and act as cellular sensors in mammals. Stretch activated ion channels (SACs) have been proposed to underlie cardiac mechano electric feedback (MEF), although the molecular entity of SAC remains unknown. There is evidence suggesting that transient receptor potential canonical 1 (TRPC1) is a stretch-activated ion channel. As a non-selective cation channel, TRPC1 may cause stretch-induced depolarization and arrhythmia and thus may contribute to the MEF of the heart. In this study, we examined the expression patterns of TRPC1 in detail at both the mRNA and protein levels in rat hearts. We isolated total RNA from the left and right atria, and the left and right ventricles, and detected TRPC1 mRNA in these tissues using reverse-transcriptase polymerase chain reaction (RT-PCR). To study the protein localization and targeting, we performed immunohistochemistry and immunofluorescence labeling with the antibody against TRPC1. TRPC1 was detected in the cardiomyocytes of the ventricle and atrium at both the mRNA and protein levels. The cell membrane and T tubule showed strong fluorescence labeling in the ventricular myocytes. Purkinje cells, the endothelial cells and smooth muscle cells of the coronary arterioles also displayed TRPC1 labeling. No TRPC1 was detected in fibroblasts. In conclusion, TRPC1 is widely expressed in the rat heart, including in working cells, Purkinje cells and vascular cells, suggesting that it plays an important role in the heart. The specific distribution pattern offered a useful insight into its function in adult rat ventricular cells. Further investigations are needed to clarify the role of TRPC1 in regulating cardiac activity, including cardiac MEF. PMID- 22073359 TI - Identification of the novel localization of tenascinX in the monkey choroid plexus and comparison with the mouse. AB - Tenascin-X (Tn-X) belongs to the tenascin family of glycoproteins and has been reported to be significantly associated with schizophrenia in a single nucleotide polymorphism analysis in humans. This finding indicates an important role of Tn-X in the central nervous system (CNS). However, details of Tn-X localization are not clear in the primate CNS. Using immunohistochemical techniques, we found novel localizations of Tn-X in the interstitial connective tissue and around blood vessels in the choroid plexus (CP) in macaque monkeys. To verify the reliability of Tn-X localization, we compared the Tn-X localization with the tenascin-C (Tn-C) localization in corresponding regions using neighbouring sections. Localization of Tn-C was not observed in CP. This result indicated consistently restricted localization of Tn-X in CP. Comparative investigations using mouse tissues showed equivalent results. Our observations provide possible insight into specific roles of Tn-X in CP for mammalian CNS function. PMID- 22073360 TI - Aromatase immunoreactivity in fetal ovine neuronal cell cultures exposed to oxidative injury. AB - A lot of evidence testifies that aromatase is expressed in the central nervous system where it has been detected not only in hypothalamic and limbic regions but also in the cerebral cortex and spinal cord. In physiological conditions, aromatase is expressed exclusively by neurons, where it has been mainly found in cell bodies, processes and synaptic terminals. Moreover, primary cultured cortical astrocytes from female rats are more resistant to oxidant cell death than those from males, suggesting a protective role of estradiol. The aim of this study was to evaluate changes in aromatase expression in response to 3-nitro-L tyrosine, a marker of oxidative stress, in primary neuronal cell cultures from brains of 60-day old sheep fetuses. Cells were identified as neurons by using class III beta-tubulin, a marker of neuronal cells. Two morphological types were consistently recognizable: i) bipolar cells with an oval cell body; ii) multipolar cells whose processes formed a wide net with those of adjacent cells. In situ hybridization technique performed on 60-day old fetal neurons revealed that in baseline conditions aromatase gene expression occurs. Importantly, cells exposed to 360 uM 3-nitro-L-tyrosine were fewer and showed more globular shape and shorter cytoplasmic processes in comparison to control cells. The immunocytochemical study with anti-aromatase antibody revealed that cells exposed to 360 uM 3-nitro-L-tyrosine were significantly more immunoreactive than control cells. Thus, it can be postulated that the oxidant effects of the amino acid analogue 3-nitro-L-tyrosine could be counterbalanced by an increase in aromatase expression that in turn can lead to the formation of neuroprotective estradiol via aromatization of testosterone. PMID- 22073361 TI - Effects of castration on the expression of the NGF and TrkA in the vas deferens and accessory male genital glands of the rat. AB - Nerve Growth Factor (NGF) is a member of the neurotrophin family. Neurotrophins exert their effects by binding to corresponding receptors, which are formed by the tyrosine protein kinases TrkA, TrkB, and TrkC, and the low affinity p75NTR receptor. The role of neurotrophins in the biology of male genital organs is far from clear. In particular, little is known about the influence of sex hormones on the expression of neurotrophins and their receptors. In the present study, using immunohistochemistry and real time RT-PCR, we investigated the expression of NGF and TrkA in the vas deferens and accessory male genital glands in normal and castrated rats.In normal rats, both NGF- and TrkA-immunoreactivities (IR) were localized in the epithelial layer of the vas deferens. NGF-IR was also found in the stroma and epithelium of the vesicular gland and prostate. TrkA-IR was distributed in the epithelial cells of vesicular and prostate glands. The nerves were weakly immunoreactive in all the examined organs. After castration the immunoreactivities increased. Real-time RT-PCR experiments indicated that NGF and TrkA mRNA levels increased significantly after castration. These results suggest that NGF and TrkA are expressed in the internal male genital organs of the rat and that their expression is downregulated by androgen hormones. We hypothesize NGF and TrkA play a role in the processes that regulate the involution of these organs under conditions of androgen deprivation. PMID- 22073362 TI - Differential expression of ryanodine receptor in the developing rat cochlea. AB - Ryanodine receptors (RyRs) are one of the intracellular calcium channels involved in regulation of intracellular free calcium concentration ([Ca(2+)]i). The immunolocalization of RyRs was investigated in the developing rat cochlea at different postnatal days (PND). The change of [Ca(2+)]i in isolated outer hair cells (OHCs) was determined. Morphological results showed low expression of RyRs in the Kolliker's organ from the PND 5 group. RyR expression in inner hair cells (IHCs) increased as the rats aged, and was mature after PND 14. RyRs in OHCs were expressed near the synaptic area of afferent and efferent nerves. RyRs in supporting cells were expressed widely and strongly. The application of ACh, ryanodine + ACh, and thapsigargin + ACh could induce a significant increase in [Ca(2+)]i in OHCs in the presence of extracellular calcium. This increase of [Ca(2+)]i induced by ACh was caused by not only the calcium influx through surface calcium channels, but also the calciuminduced calcium release (CICR) from intracellular RyR-sensitive calcium stores. Morphological and Ca imaging results suggested that RyRs expression is related to cochlear maturity, and may play an important role in its function. PMID- 22073363 TI - Proteomics-based investigation in C2C12 myoblast differentiation. AB - Skeletal muscle cell differentiation is a multistage process extensively studied over the years. Even if great improvements have been achieved in defining biological process underlying myogenesis, many molecular mechanisms need still to be clarified.To further highlight this process, we studied cells at undifferentiated, intermediate and highly differentiated stages, and we analyzed, for each condition, morphological and proteomic changes. We also identified the proteins that showed statistical significant changes by a ESI-Q-TOF mass spectrometer. This work provides further evidence of the involvement of particular proteins in skeletal muscle development. Furthermore, the high level of expression of many heat shock proteins, suggests a relationship between differentiation and cellular stress. Intriguingly, the discovery of myogenesis correlated proteins, known to play a role in apoptosis, suggests a link between differentiation and this type of cell death. PMID- 22073364 TI - Cytokeratin 20-positive hepatocellular carcinoma. AB - The differential diagnosis between hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and metastatic colorectal adenocarcinoma (MCA) may be difficult when only based on morphology. For this purpose immunohistochemical analyses are often required, utilizing antibodies directed against CK8-18, Hep Par1, glypican 3, CK7, CK19, CK20. Here we report a case of a 65-year-old man who presented with a clinical picture of decompensated cirrhosis. Ultrasonography revealed two nodular areas in the right liver lobe. Liver needle biopsy revealed micro-macronodular cirrhosis associated with HCC with trabecular and pseudoglandular patterns. Immunohistochemically, tumour cells were diffusely positive for CK8-18 and also diffusely immunostained by glypican 3 and Hep-Par1. Interestingly, a diffuse and strong staining for CK20 was detected in the vast majority of tumor cells, particularly in the areas showing a pseudo-glandular pattern. No immunostaining for CK7 and CK19 was found in the tumor cells. The tumor behaved aggressively, with a rapid diffusion to the whole liver. The patient died from the disease few months after presentation. These findings underline that the interpretation of the expression of CK20 alone in the differential diagnosis among HCC, CC and MCA should be done with caution because a diffuse immunoreactivity for CK20 alone may not rule out the diagnosis of HCC. PMID- 22073365 TI - Merkel cell carcinoma with an unusual immunohistochemical profile. AB - The clinical and morphological picture of Merkel cell carcinoma (MCC) may be rather challenging; therefore, the immunohistochemical profile plays a relevant role in confirming the microscopic diagnosis. A panel of antibodies including cytokeratins 20, 7 and epithelial membrane antigen, and neuron-specific enolase is used in confirming the morphological diagnosis of MCC. The majority of MCCs express CK20 and are CK7-negative. Herein, we present a case of primary cutaneous neuroendocrine carcinoma with an atypical immunohistochemical pattern. A 83-years old woman presented with a painless plaque, red to violaceous in colour, located in the leg. The skin tumor was excided, formalin-fixed and paraffinembedded. Tissue sections were immunostained with a panel of antibodies routinely utilized in complex primary skin tumors for evidencing epithelial and neuroendocrine differentiation of tumor cells. The neuroendocrine differentiation of tumor cells was evidenced by their immunoreactivity for synaptophysin, chromograninA and neuron-specific enolase. Tumor cells also showed diffuse cytoplasmic staining for CK7. No immunoreactivity was detected for CK20 and thyroid transcription factor 1. Our data, together with previous rare reports of CK20-/CK7+ MCCs, lay stress on the importance of routinely utilizing a panel of antibodies in the differential diagnosis of complex primary carcinomas of the skin and may have important implications in expanding the differential diagnosis of skin tumors. In particular, caution should be taken in excluding the diagnosis of MCC only on the basis of the absence of reactivity of tumor cells for CK20, favouring the wrong diagnosis of less aggressive skin tumors. PMID- 22073366 TI - Increased number of intestinal villous M cells in levamisole -pretreated weaned pigs experimentally infected with F4ac+ enterotoxigenic Escherichia coli strain. AB - Immunoprophylaxis of porcine postweaning colibacillosis (PWC) caused by enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbriae is an unsolved problem. Just as ETEC strains can exploit intestinal microfold (M) cells as the entry portal for infection, their high transcytotic ability make them an attractive target for mucosally delivered vaccines, adjuvants and therapeutics. We have developed a model of parenteral/oral immunization of 4-weeks-old pigs with either levamisole or vaccine candidate F4ac(+) non-ETEC strain to study their effects on de novo differentiation of antigen-sampling M cells. Identification, localization and morphometric quantification of cytokeratin 18 positive M cells in the ileal mucosa of 6-weeks-old pigs revealed that they were: 1) exclusively located within villous epithelial layer, 2) significantly numerous (P< 0.01) in levamisole pretreated/challenged pigs, and 3) only slightly, but not significantly numerous in vaccinated/challenged pigs compared with non pretreated/challenged control pigs. The fact that levamisole may affect the M cells frequency by increasing their numbers, makes it an interesting adjuvant to study development of an effective M cell-targeted vaccine against porcine PWC. PMID- 22073367 TI - Expression of lumican and fibromodulin following interleukin-1 beta stimulation of disc cells of the human temporomandibular joint. AB - Small leucine-rich repeat proteoglycans (SLRP) are present in the extracellular matrix of the temporomandibular joint (TMJ) disc. Lumican and fibromodulin, classified as class 2 SLRPs, play important roles in TMJ assembly, proliferation and inflammation. Degenerative change in the TMJ disc gives rise to the process of internal derangement (ID). In this study, we immunohistochemically examined the expression of lumican and fibromodulin in nine human TMJ specimens and examined the gene expression of both proteoglycans in cultured human TMJ disc cells under interleukin-1 beta (IL-1 beta)-stimulated conditions. An articular disc cell line was established by collagenase treatment of a TMJ disc. The subcultured cells were then incubated for 1, 3, 6, 12, 24 or 48 h under both normal and IL-1 beta (1 ng/mL) conditions. The gene expression of lumican and fibromodulin was examined using the reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR. We demonstrated that the expression of lumican significantly differs from that of fibromodulin in the deformed disc and that IL-1 beta induces a significant increase in lumican mRNA, but not in fibromodulin mRNA, after 24~48 h culture compared to cells cultured in the absence of IL-1 beta (P<0.05). These results indicate that lumican and fibromodulin display different behaviors and that lumican may promote regeneration of the TMJ after degeneration and deformation induced by IL-1 beta. PMID- 22073368 TI - Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients. AB - Multiple myeloma (MM) is a malignant plasma cell disease. Several proinflammatory cytokines produced by malignant plasma cells and bone marrow (BM) stromal cells are involved in the pathogenesis of the disease. We evaluated serum levels of the proinflammatory cytokines Interleukin-1beta (IL-1beta), Interleukin-6 (IL-6), Interleukin-8 (IL-8), macrophage inflammatory protein-1alpha (MIP-1alpha), in MM patients before treatment, and determined its significance in tumor progression. We also analyzed the correlation between measured parameters with proliferating cell nuclear antigen (PCNA). Forty-four MM patients and 20 healthy controls were studied. Serum levels of the proinflammatory cytokines were measured using enzyme linked immunosorbent assay (ELISA), whereas PCNA value in the BM was determined by immunohistochemistry staining. The mean concentrations of the measured cytokines were significantly different among the three stages of disease, with higher values in advanced disease stage. Furthermore, patients with MM had significantly higher serum levels of the measured cytokines than in controls. A positive correlation was found between IL-6 with IL-1beta, IL-8 and MIP-1alpha. Similarly, IL-8 and MIP-1alpha were positively correlated with markers of disease activity such as beta2 microglobulin and LDH. The proliferation index, determined by PCNA immunostaining, was higher in advanced disease stage. Furthermore PCNA value correlated significantly with beta2 microglobulin, LDH and the levels of the measured cytokines. Our results showed that the proliferative activity, as measured with PCNA, increases in parallel with disease stage. The positive correlation between PCNA and other measured mediators supports the involvement of these factors in the biology of myeloma cell growth and can be used as markers of disease activity and as possible therapeutic targets. PMID- 22073369 TI - Influence of surgical and chemical orchidectomy on weight and distribution of AChE-nerve fibres in thymuses of adult rats. AB - The thymus is a crossroad between the immune and neuroendocrine systems. As such, it is innervated by acetylcholinesterase (AChE)-positive fibres of the vagus, the recurrent laryngeal and the phrenic nerves. It is well know, that the innervations density of the thymus increases with age. In our study, adult rats were orchidectomized (surgically and chemically by the application of a luteinizing hormone-releasing hormone). The density of AChE-positive nerve fibres in thymuses, as well as the weight of thymuses was examined. The authors found that both surgical and chemical orchidectomy result in macroscopic and microscopic regeneration of the atrophied thymuses. In regenerated rat's thymuses after orchidectomy the density of AChE-positive nerve fibres was markedly higher in comparison with the control animals. The distribution, as well as the density of AChE-positive nerve fibres in regenerated thymuses after orchidectomy evokes the images of its innervations like in young animals before age-related involution. The authors also found a markedly higher weight of thymuses of orchidectomized rats in comparison with the control groups. In recent study the authors proved that after 8 weeks surgical orchidectomy leads to the regeneration of thymic AChE-positive innervation and chemical orchidectomy by administration of luteinizing hormone-releasing hormone after 4 weeks of adult rats. PMID- 22073370 TI - NADPH-diaphorase expression in the rat jejunum after intestinal ischemia/reperfusion. AB - The purpose of this study was to analyze the nicotinamide adenine dinucleotide phosphate - diaphorase (NADPH-d) activity in the rat jejunum after a mesenteric ischemia/reperfusion injury. Nitric oxide, synthetised from L-arginine by the enzyme nitric oxide synthase, is a nonadrenergic noncholinergic relaxant neurotransmitter of the intestinal smooth muscle. It plays an important role in the process of plasticity after the ischemia/reperfusion injury. Experimental animals were divided in two groups: the control group and the ischemic/reperfusion group, with different period of the reperfusion. The NADPH-d histochemical method has been used as a marker for the nitric oxide synthase. NADPH-d activity has been rapidly decreased in the neurons of both enteric nervous systems in plexuses of the jejunum after 1 h mesenteric ischemia and 1 h reperfusion. Differences were predominantly detected in the myenteric plexus; they were seen in change of the neuronal shape, in the arrangement of neurons and in intensity of their staining. The NADPH-d positivity was absent in the intestinal crypts. After 1 h ischemia and 24 h reperfusion, the NADPH-d activity was gradually increased, but it was lower in comparison with the control group. On the 30th day following the ischemia/reperfusion there were no changes in NADPH d positivity compared with the control animals. These results indicated that the jejunal ischemia/reperfusion has affected the neurons of the enteric nervous system of adult rats and resulted in the early decrease of NADPH-d positivity 1 h of the reperfusion insult. The gradual increasing of NADPH-d activity in 24 h following the reperfusion could be considered as a result of the plasticity process. On the 30(th) day after the ischemia/reperfusion all histochemical changes were returned to the control levels. PMID- 22073371 TI - Immunohistochemical expression of types I and III collagen antibodies in the temporomandibular joint disc of human foetuses. AB - The objective was to study the morphology of the articular disc and analyse the immunohistochemical expression of types I and III collagen markers in the temporomandibular joint (TMJ) disc of human foetuses of different gestational ages. Twenty TMJ from human foetuses supplied by Universidade Federal de Uberaba with gestational ages from 17 to 24 weeks were studied. The gestational age of the foetuses was determined by measuring the crown-rump (CR) length. Macroscopically, the foetuses were fixed in 10% formalin solution and dissected by removing the skin and subcutaneous tissue and exposing the deep structures. Immunohistochemical markers of type I and III were used to characterize the existence of collagen fibres. Analysis of the immunohistochemical markers of types I and III collagen revealed the presence of heterotypical fibril networks. PMID- 22073372 TI - Expression pattern of thymosin beta 4 in the adult human liver. AB - Thymosin beta-4 (Tbeta4) is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tbeta4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tbeta4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tbeta4 commercial antibody. Tbeta4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tbeta4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1). At higher power, Tbeta4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tbeta4. The current work first evidences a strong diffuse expression of Tbeta4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tbeta4 in adulthood. Moreover, Tbeta4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tbeta4. PMID- 22073374 TI - Expression of progesterone receptor membrane component-1 in bovine reproductive system during estrous cycle. AB - Several reports suggest the participation of progesterone receptor membrane component 1 (PGRMC1) in progesterone signaling in the reproductive system. This study aimed at investigating the presence and localization of PGRMC1 in bovine ovary, oviduct and uterus, during the follicular and luteal phases of the estrous cycle. In the ovary, PGRMC1 has been detected in surface germinal epithelium, granulosa cells, theca cells and in the germinal vesicle of the oocytes at all stages of folliculogenesis. In the corpus luteum the expression of PGRMC1 was influenced by the stage of the estrous cycle. In the oviducts and in the uterus horns, PGRMC1 was immunolocalized in the luminal epithelium, in the muscle layer cells and in the endothelial cells. In the uterus, PGRMC1 was intensely localized also in the glandular endometrium. However, in the oviducts and in the uterus horns, the localization of PGRMC1 was independent on the stage of the estrous cycle and on whether evaluating the ipsilateral or the contralateral organ. In conclusion, the present immunohistochemical study showed that PGRMC1 is located in various compartments of the bovine female reproductive organs. With the exception of the corpora lutea, PGRMC1 localization showed similar pattern during different stages of the estrous cycle. PMID- 22073375 TI - Constitutive heterochromatin polymorphisms in human chromosomes identified by whole comparative genomic hybridization. AB - Whole comparative genomic hybridization (W-CGH) is a new technique that reveals cryptic differences in highly repetitive DNA sequences, when different genomes are compared using metaphase or interphase chromosomes. W-CGH provides a quick approach to identify differential expansion of these DNA sequences at the single chromosome level in the whole genome. In this study, we have determined the frequency of constitutive chromatin polymorphisms in the centromeric regions of human chromosomes using a whole-genome in situ cross-hybridization method to compare the whole genome of five different unrelated individuals. Results showed that the pericentromeric constitutive heterochromatin of chromosome 6 exhibited a high incidence of polymorphisms in repetitive DNA families located in pericentromeric regions. The constitutive heterochromatin of chromosomes 5 and 9 was also identified as highly polymorphic. Although further studies are necessary to corroborate and assess the overall incidence of these polymorphisms in human populations, the use of W-CGH could be pertinent and of clinical relevance to assess rapidly, from a chromosomal viewpoint, genome similarities and differences in closely related genomes such as those of relatives, or in more specific situations such as bone marrow transplantation where chimerism is produced in the recipient. PMID- 22073373 TI - Cultured myoblasts from patients affected by myotonic dystrophy type 2 exhibit senescence-related features: ultrastructural evidence. AB - Myotonic dystrophy type 2 (DM2) is an autosomal dominant disorder caused by the expansion of the tetranucleotidic repeat (CCTG)n in the first intron of the Zinc Finger Protein-9 gene. In DM2 tissues, the expanded mutant transcripts accumulate in nuclear focal aggregates where splicing factors are sequestered, thus affecting mRNA processing. Interestingly, the ultrastructural alterations in the splicing machinery observed in the myonuclei of DM2 skeletal muscles are reminiscent of the nuclear changes occurring in age-related muscle atrophy. Here, we investigated in vitro structural and functional features of satellite cell derived myoblasts from biceps brachii, in the attempt to investigate cell senescence indices in DM2 patients by ultrastructural cytochemistry. We observed that in satellite cell-derived DM2 myoblasts, cell-senescence alterations such as cytoplasmic vacuolization, reduction of the proteosynthetic apparatus, accumulation of heterochromatin and impairment of the pre-mRNA maturation pathways occur earlier than in myoblasts from healthy patients. These results, together with preliminary in vitro observations on the early onset of defective structural features in DM2 myoblast derived-myotubes, suggest that the regeneration capability of DM2 satellite cells may be impaired, thus contributing to the muscular dystrophy in DM2 patients. PMID- 22073376 TI - Histochemical properties of sialic acids and antimicrobial substances in canine anal glands. AB - The functional properties of sialic acids appear to be manifold. Additionally, antimicrobial substances serve as a non-specific defense against microorganisms. In this study, therefore, the localization of sialic acids and antimicrobial substances in the anal glands of dog was studied by sialoglycoconjugate histochemistry and immunohistochemistry. The secretory epithelium, luminal secretions and excretory ducts exhibited high levels of sialoglycoconjugates that terminated in Siaalpha2-6Gal/GalNAc or Siaalpha2-3Gal1-4GlcNAc. Additionally, O acetylated sialic acids were detectable in these glandular structures. Antimicrobial substances, such as lysozyme, immunoglobulin A (IgA), lactoferrin and the peptide group of beta-defensins, were also demonstrated as products of the anal glands. The results obtained are discussed with regard to the functional significance of the anal glands. These secretory products may create a defensive barrier against microbial invasion at the anal mucosa. PMID- 22073377 TI - Lubricin is expressed in chondrocytes derived from osteoarthritic cartilage encapsulated in poly (ethylene glycol) diacrylate scaffold. AB - Osteoarthritis (OA) is characterized by degenerative changes within joints that involved quantitative and/or qualitative alterations of cartilage and synovial fluid lubricin, a mucinous glycoprotein secreted by synovial fibroblasts and chondrocytes. Modern therapeutic methods, including tissue-engineering techniques, have been used to treat mechanical damage of the articular cartilage but to date there is no specific and effective treatment. This study aimed at investigating lubricin immunohistochemical expression in cartilage explant from normal and OA patients and in cartilage constructions formed by Poly (ethylene glycol) (PEG) based hydrogels (PEG-DA) encapsulated OA chondrocytes. The expression levels of lubricin were studied by immunohistochemistry: i) in tissue explanted from OA and normal human cartilage; ii) in chondrocytes encapsulated in hydrogel PEGDA from OA and normal human cartilage. Moreover, immunocytochemical and western blot analysis were performed in monolayer cells from OA and normal cartilage. The results showed an increased expression of lubricin in explanted tissue and in monolayer cells from normal cartilage, and a decreased expression of lubricin in OA cartilage. The chondrocytes from OA cartilage after 5 weeks of culture in hydrogels (PEGDA) showed an increased expression of lubricin compared with the control cartilage. The present study demonstrated that OA chondrocytes encapsulated in PEGDA, grown in the scaffold and were able to restore lubricin biosynthesis. Thus our results suggest the possibility of applying autologous cell transplantation in conjunction with scaffold materials for repairing cartilage lesions in patients with OA to reduce at least the progression of the disease. PMID- 22073378 TI - Cancer Tissue Engineering: A Novel 3D Polystyrene Scaffold for In Vitro Isolation and Amplification of Lymphoma Cancer Cells from Heterogeneous Cell Mixtures. AB - Isolation and amplification of primary lymphoma cells in vitro setting is technically and biologically challenging task. To optimize culture environment and mimic in vivo conditions, lymphoma cell lines were used as a test case and were grown in 3-dimension (3D) using a novel 3D tissue culture polystyrene scaffold with neonatal stromal cells to represent a lymphoma microenvironment. In this model, the cell proliferation was enhanced more than 200-fold or 20,000% neoplastic surplus in 7 days when less than 1% lymphoma cells were cocultured with 100-fold excess of neonatal stroma cells, representing 3.2-fold higher proliferative rate than 2D coculture model. The lymphoma cells grew and aggregated to form clusters during 3D coculture and did not maintained the parental phenotype to grow in single-cell suspension. The cluster size was over 5 fold bigger in the 3D coculture by day 4 than 2D coculture system and contained less than 0.00001% of neonatal fibroblast trace. This preliminary data indicate that novel 3D scaffold geometry and coculturing environment can be customized to amplify primary cancer cells from blood or tissues related to hematological cancer and subsequently used for personalized drug screening procedures. PMID- 22073379 TI - The Chemical and Physical Properties of Poly(epsilon-caprolactone) Scaffolds Functionalised with Poly(vinyl phosphonic acid-co-acrylic acid). AB - There is a clinical need for a synthetic alternative to bone graft substitute (BGS) derived from demineralised bone matrix. We report the electrospinning of Poly(epsilon-caprolactone) (PCL) to form a 3-dimensional scaffold for use as a synthetic BGS. Additionally, we have used Poly(vinyl phosphonic acid-co-acrylic acid) (PVPA) to improve bone formation. Fibres were formed using a 10% w/v PCL/acetone solution. Infrared spectroscopy confirmed that the electrospinning process had no effect on the functional groups present in the resulting structure. The electrospun scaffolds were coated with PVPA (PCL/PVPA), and characterised. The stability of the PVPA coating after immersion in culture medium was assessed over 21 days. There was rapid release of the coating until day 2, after which the coating became stable. The wettability of the PCL scaffolds improved significantly, from 123.3 +/- 10.8 degrees to 43.3 +/- 1.2 degrees after functionalisation with PVPA. The compressive strength of the PCL/PVPA scaffolds (72 MPa) was significantly higher to that of the PCL scaffold (14 MPa), and an intermediate between trabecular and cortical bone (7 MPa and 170 MPa, resp.). The study has demonstrated that the PCL/PVPA scaffold has the desired chemical and biomechanical characteristics required for a material designed to be used as a BGS. PMID- 22073380 TI - Factor structure of manic symptoms in adolescents. AB - OBJECTIVE: To identify the factor structure of manic symptoms in adolescents as assessed by the Scale for Manic States (SMS). METHOD: Pattern of symptoms was assessed in a group of 100 adolescents with a diagnosis of manic episode as defined by the International Classification of Diseases, 10th revision - Diagnostic Criteria for Research. A principal component analysis of the broad range of psychiatric symptoms covered by the SMS was conducted. RESULTS: Seven eigenvalues were greater than unity, and parallel analysis revealed 5 factors, whereas scree plot was inconclusive. Five-factor solution as obtained by parallel analysis was chosen, which described our data appropriately and were clinically relevant. The 5 factors were: aggressive overactivity, dysphoria, psychosis, hedonia, and thought retardation. These captured 58.14% of the total variance. CONCLUSIONS: These 5 factors explain the clinical dimensions in adolescent mania similar to those of the adult population. Nevertheless, certain features, such as presence of psychosis along with euphoric mood and thought retardation, distinguish adolescent from adult mania. PMID- 22073381 TI - An open-label trial of acamprosate in the treatment of pathological gambling. AB - BACKGROUND: The efficacy and tolerability of acamprosate has been tested in the treatment of pathological gambling (PG). Acamprosate is known to reduce alcohol craving and use in persons with alcohol dependence, and it has been hypothesized that the drug would have a similar effect in individuals with PG. METHODS: Participants with DSM-IV criteria for PG received acamprosate in an 8-week, open label trial following a 2-week observation. The primary efficacy measure was the Yale-Brown Obsessive Compulsive Scale modified for PG (Y-BOCS-PG). Secondary efficacy measures included the Gambling Severity Assessment Scale (GSAS), the Clinical Global Impression (CGI) Improvement and Severity Scales, a patient self rated global rating, the Hamilton Depression Rating Scale (HDRS), the Sheehan Disability Scale (SDS), and the Timeline Follow Back (TLFB). The study was conducted at 2 sites. RESULTS: Twenty-six participants (11 men, 15 women) had at least 1 post-baseline visit and were included in the analysis. Twenty participants (77%) completed the protocol. Significant improvement was observed in Y-BOCS-PG and GSAS scores, both CGI scales, a patient self-rated global scale, all 3 SDS subscales, and number of gambling episodes. Seventeen participants (65%) were considered responders (ie, achieved "much" or "very much" improvement). Improvements on the HDRS, in money wagered, and in time spent gambling were not significant. Few adverse events were reported. CONCLUSIONS: The results suggest that acamprosate is well tolerated and may be effective in the treatment of PG. PMID- 22073382 TI - Clinically insubstantial cognitive side effects of bitemporal electroconvulsive therapy at 0.5 msec pulse width. AB - BACKGROUND: We measured cognitive side effects from bitemporal electroconvulsive therapy (ECT) using stimuli of 0.5 msec pulse width 900 milliamperes (mA). METHODS: Mini-Mental State Exam (MMSE) and 21-item Hamilton Rating Scale for Depression (HRSD-21) were rated within 36 hours before and 36 hours after a series of 6 bitemporal ECT sessions on 15 patients age >=45. RESULTS: MMSE remained high after ECT (pre-ECT mean 29, standard deviation [SD] 1.60, post-ECT mean 28.53, SD 1.36) with no significant change. The mean HRSD-21 fell from 27.5 to 16.3. Post-ECT MMSE was significantly and markedly higher than in previous studies of bitemporal ECT; all had used ECT stimuli of pulse width at least 1 msec. CONCLUSIONS: With stimuli of 0.5 msec pulse width and 900 mA, 6 bitemporal ECTs did not decrease MMSE score. This result leaves no opportunity for further decrease in basic cognitive side effects, and complements published reports of stronger physiological effects with stimuli of 0.5 msec pulse width and 900 mA. ECT stimuli of 0.5 msec pulse width and 900 mA are more desirable than wider pulse widths. Six bitemporal ECT sessions using these stimuli generally will not have more cognitive side effects than treatments with other placements, allowing maintenance of full efficacy with clinically insubstantial side effects. PMID- 22073383 TI - Psychiatric comorbidity and treatment response in patients with tuberous sclerosis complex. AB - BACKGROUND: Behavioral and psychiatric comorbidity are common in tuberous sclerosis complex (TSC), but information regarding psychopharmacologic management is lacking. METHODS: We reviewed clinical records of patients evaluated over a 20 month period at a large, quaternary referral center specializing in the comprehensive management of patients with TSC. Data were collected regarding psychiatric diagnoses, psychopharmacologic medications used to treat these disorders, and clinical response to treatment at follow-up. RESULTS: There were 113 encounters by 62 pediatric and adult patients with TSC, which were included in the present analysis. Behavioral and anxiety disorders were most prevalent, as were autism spectrum disorders and attention-deficit/hyperactivity disorder. Antipsychotics, antidepressants, and anticonvulsants with mood-stabilizing properties were the most often prescribed psychoactive medications and were associated with an overall improvement or stabilization of psychiatric symptoms 65% of the time. CONCLUSIONS: Psychiatric comorbidity, especially behavioral disorders, is very common among patients with TSC. Pharmacologic treatment can be very effective and should be considered for optimal disease management in affected individuals. PMID- 22073384 TI - An open-label trial of aripiprazole in the treatment of aggression in male adolescents diagnosed with conduct disorder. AB - BACKGROUND: The adverse effect profiles of typical and atypical antipsychotics are problematic because of their extrapyramidal and endocrine adverse effects, respectively. METHODS: Ten adolescent male patients diagnosed with conduct disorder received aripiprazole in doses of <=20 mg/d in an open-label, intent-to treat design to establish and characterize the efficacy of the drug in reducing aggressive behavior. RESULTS: Based on clinician and parent observations, aripiprazole was effective in reducing aggressive behavior in adolescent boys. The change in clinician-observed aggression ratings appears to have been driven by a decrease in physical aggression, whereas the change in parent-observed aggression ratings appears to have been driven by a decrease in verbal aggression and aggression against objects and animals. CONCLUSIONS: Aripiprazole was an effective and relatively well-tolerated treatment for overall aggression in adolescent males with conduct disorder, in the view of both clinicians and parents. Depending on the observer, aripiprazole improved aggression categorized as physical aggression, verbal aggression, and aggression against objects and animals. PMID- 22073385 TI - Treatment of depression associated with age-related macular degeneration: a double-blind, randomized, controlled study. AB - BACKGROUND: Depression is frequently found in patients with age-related macular degeneration (AMD). The purpose of this study was to assess the effectiveness of escitalopram in treating major and minor depression in AMD patients. METHODS: We conducted a crossover, randomized, double-blind, placebo-controlled, 16-week study comparing escitalopram with placebo. Inclusion criteria included reduced vision from AMD and major or minor depression, with a 17-item Hamilton Rating Scale for Depression (HAMD-17) score of >=10. Participants were randomly assigned to receive either escitalopram or placebo for 8 weeks and then crossed over to the other treatment. The primary outcome was change on the total HAMD-17 score with escitalopram treatment compared with placebo. RESULTS: We enrolled 16 AMD patients (mean age 79.1), 12 with major depression and 4 with minor depression. Mean HAMD-17 score at enrollment was 16.1 +/- 4.2, and mean visual acuity in the better eye was 20/70. During escitalopram treatment, participants showed a significant reduction in HAMD-17 scores compared with placebo treatment (P = .01). CONCLUSIONS: These findings suggest escitalopram may be an effective treatment for depressive symptoms associated with major or minor depression in AMD patients with vision loss. PMID- 22073386 TI - Patients with obsessive-compulsive disorder vs depression have comparable health care costs: a retrospective claims analysis of Florida Medicaid enrollees. AB - BACKGROUND: The health care burden of obsessive-compulsive disorder (OCD) is relatively unknown. OBJECTIVE: To compare the health care burden of patients with OCD vs depression. METHODS: This retrospective claims analysis compared the 2 year median per-patient health care claims and costs for Florida Medicaid adult enrollees (1997 to 2006) newly diagnosed with "pure OCD" (P-OCD; OCD without comorbid major depression, bipolar disorder, psychosis, organic mental disorder, pervasive developmental disorder, nonpsychotic brain damage, developmental delay, or mental retardation) with matched patients newly diagnosed with "pure depression" (P-D; similar to P-OCD but excluding OCD instead of depression). RESULTS: Eighty-five newly diagnosed P-OCD patients were matched with 14,906 P-D patients. Although median per-patient total health care costs were comparable across groups, patients with P-D incurred significantly higher median outpatient medical costs ($1,928 vs $363, P = .003), while those with P-OCD incurred almost three-fold greater psychiatric costs ($2,028 vs $759, P < .0001). The latter was due primarily to significantly higher costs of psychotropic medications among those with P-OCD ($4,307 vs $2,317, P = .0006) rather than to psychiatric outpatient care. CONCLUSIONS: Patients with P-D and P-OCD carry a similar burden in overall health care costs. However, the burden of those with P-D was largely attributable to outpatient medical costs while that of those with P-OCD was due to higher costs of psychotropic medications. PMID- 22073387 TI - Empirical findings on legal difficulties among practicing psychiatrists. AB - BACKGROUND: This article reviews the published literature on areas of legal difficulty among practicing psychiatrists. METHODS: A literature search using PubMed identified studies of malpractice lawsuits or medical board discipline of psychiatrists between 1990 and 2009. Eight studies of physician discipline in the United States and one from the United Kingdom were identified. Information from 3 insurance companies and 3 sets of aggregated insurance company data also were available. One follow-up study of hospitalized psychiatric patients also was reviewed. RESULTS: Studies of medical board discipline indicate that, compared with other specialties, psychiatrists are at an increased risk of disciplinary action. Psychiatrists who were female, board certified, and in practice for a short period of time had a lower chance of medical board discipline. Psychiatry claims accounted for a very small proportion of overall malpractice claims and settlements. The amount of patient disability secondary to alleged malpractice was the most important variable predicting insurance payout. CONCLUSIONS: Psychiatrists appear to be disciplined by medical boards at an above-average frequency compared with other medical specialties. However, few malpractice suits reach the courts, and psychiatry represents a very small proportion of overall physician malpractice claims and dollars of settlement. PMID- 22073388 TI - Differential diagnosis of tardive dyskinesia in an older woman taking antipsychotic medication. PMID- 22073389 TI - Magnetically immobilized nanoporous giant proteoliposomes as a platform for biosensing. AB - We report a biosensing method that is based on magnetically immobilized functional liposomes. The vesicles encapsulate magnetic nanoparticles (MNP) and enzymatic sensing reagents. Magnetic attraction between MNP and external magnets first immobilizes liposomes onto the surface of a coverglass. With the assistance from alpha-hemolysin (aHL), translocations of analytes through a lipid membrane trigger intravesicular enzymatic reactions. After 90 s incubation, the product from the sensing reactions, resorufin, was probed by laser-induced fluorescence. Detection of two analytes, glucose and ethanol, was demonstrated using two types of functional vesicles. The effects of MNP-containing vesicles and biotinylated vesicles on aHL's translocations of analytes were also compared. Unlike biotinylated lipids, MNP facilitate immobilization of liposomes without compromising the integrity of membrane and pore-forming activity of aHL. PMID- 22073390 TI - Varying molecular interactions by coverage in supramolecular surface chemistry. AB - The possibility of modifying the intermolecular interactions of absorbed benzene carboxylic acids from coordination to hydrogen bonding by changing their surface coverage is demonstrated through a combination of scanning tunnelling microscopy, X-ray photoemission spectroscopy and density functional theory calculations. PMID- 22073391 TI - Interaction of niobium and tantalum pentahalides with O-donors: coordination chemistry and activation reactions. AB - The chemistry of niobium and tantalum pentahalides, MX(5), with oxygen compounds is reviewed herein. The polynuclear structure of MX(5) is readily broken by addition of oxygen-containing organic molecules, L, to give either mononuclear or ionic dinuclear coordination adducts. Then activation of the organic ligand may take place favoured by several factors, i.e. low M-X bond energy, high temperature, presence of more than one oxygen function within L, L/M molar ratio >= 2. The activation reactions are often uncommon in the context of metal halides; they include the cleavage of C(sp3)-O, C(sp2)-O, C-H and C-C bonds, and eventual successive rearrangements proceeding with C-O or C-C couplings. The recently elucidated reactivity of MX(5) with limited amounts of oxygen compounds will be presented, and possible connections with the relevant MX(5)-directed syntheses reported in the literature will be outlined. PMID- 22073392 TI - First enantiospecific synthesis of marine sesquiterpene quinol akaol A. AB - The first enantiospecific synthesis of akaol A, a marine sesquiterpene quinol, has been achieved. Key steps of the synthetic sequence are the oxidative degradation of (-)-sclareol to a dinorlabdane ketoester, mediated by the ozone lead(IV) acetate system, the diastereoselective alpha-methylation of a ketoaldehyde, followed by an intramolecular aldol condensation and the further Diels-Alder cycloaddition of a dienol ether. PMID- 22073393 TI - Bright blue emissions with temperature-dependent quantum yields from microporous metal-organic frameworks. AB - Two 2D microporous metal-organic frameworks have been assembled from a fluorophore ligand, whose quantum yields of strong blue emissions could vary from 40.3% to 74.5% and 13.7% to 25.8% with the decreasing temperature. PMID- 22073394 TI - (BEDT-TTF)3Cu2(C2O4)3(CH3OH)2: an organic-inorganic hybrid antiferromagnetic semiconductor. AB - An organic-inorganic hybrid combining a semiconducting BEDT-TTF layer and a Jahn Teller distorted oxalato-bridged honeycomb antiferromagnetic layer [Cu(2)(C(2)O(4))(3)(2-)](n) was obtained and characterized. PMID- 22073395 TI - Extraction of ionic liquids from aqueous solutions by humic acid: an environmentally benign, inexpensive and simple procedure. AB - A highly effective method for the extraction of ionic liquids from aqueous solutions has been successfully developed by the formation of associates of ionic liquids with humic acid, resulted mainly from their strong electrostatic interactions. PMID- 22073396 TI - Development of asymmetric phosphine-promoted annulations of allenes with electron deficient olefins and imines. AB - Asymmetric annulation of allenes with electron-deficient olefins and imines is one of the most important reactions for the synthesis of optically active carbo- and heterocycles, which are useful building blocks for the synthesis of natural products and medicinally important substances. The use of chiral phosphines as enantioselective catalysts can be envisaged for such cyclizations. This article focuses on the important developments concerning asymmetric annulations of allenes with unsaturated partners in the recent decades and on the perspectives that these new developments offer. PMID- 22073397 TI - A novel gated photochromic reactivity controlled by complexation/dissociation with BF3. AB - A photochemically active dithiazolethene BN was designed and synthesized, exhibiting a specific gated photochromism. That is, the photochromic reactivity of BN is prevented to a great extent by BF(3), showing a "Lock" gate. PMID- 22073398 TI - Facile preparation of controllable size monodisperse anatase titania nanoparticles. AB - Monodisperse anatase titania nanoparticles with controllable sizes (typically 10 300 nm) can be synthesized using an efficient and straightforward protocol via fine tuning of the ionic strength in the devised sol-gel methodology. PMID- 22073399 TI - A computational study of organic polyradicals stabilized by chromium atoms. AB - Density functional theory has been used to investigate the properties of organic high spin molecules. The M05/cc-pVDZ calculations predict a septet ground state for the 2,3,6,7,10,11-hexahydro-1,4,5,8,9,12-hexaoxocoronene-2,3,6,7,10,11-hexayl radical (coronene-6O). The computations show further that the formation of intermolecular carbon-carbon bonds yields a singlet ground state for the dimer rather than a possible tridectet state as expected from the monomer's multiplicity. A benzene molecule placed between coronene-6O molecules leads to the desired high-spin cluster, but the overall stability of the cluster is low. A chromium atom inserted between two peripheral C(6) rings of coronene-6O yields a sandwich structure with the expected tridectet ground state and a binding energy which is 15 times larger than the corresponding tridectet dimer stabilized by a benzene molecule. The presented DFT calculations suggest that a chromium atom can effectively link organic polyradicals to larger magnetic units. PMID- 22073400 TI - Atmospheric hydrocarbon activation by the hydroxyl radical: a simple yet accurate computational protocol for calculating rate coefficients. AB - The overall rate coefficient at standard temperature and pressure for the hydrogen abstraction reaction by the hydroxyl radical (HO) from common saturated volatile organic compounds (VOCs) is derived theoretically using electronic structure calculations and transition state theory (TST). The computational approach used is based on relatively efficient methods, and hence is applicable to a large number of compounds with only a modest use of computer resources. The key methods used are density functional theory (for the calculation of barrier heights) and simple transition state theory (TST), including a simple correction for tunnelling. All thermally relevant conformers of the reactant and the abstraction TS are included in the study. For all compounds in a test set of thirty-four, the calculated rate coefficient agrees with the experimental value to within better than an order of magnitude, and to within better than a factor of three for all but six cases, so that the accuracy is of predictive utility. PMID- 22073401 TI - Recovered LiCoO2 as anode materials for Ni/Co power batteries. AB - LiCoO(2) material is recovered from spent lithium-ion batteries and investigated as anode materials for Ni/Co power batteries for the first time. LiCoO(2) electrodes with a small amount of S-doping display excellent electrochemical properties. The electrochemical reactions occurring on M0 electrodes during the first several cycles and after being activated are proposed, respectively. A function mechanism of S powder on M10 electrode is also proposed. PMID- 22073402 TI - Sub-100 fs charge transfer in a novel donor-acceptor-donor triad organized in a smectic film. AB - Ultrafast transient absorption spectroscopy is performed on a novel donor acceptor-donor triad made of two identical bisthiophene derivatives as electron donors and a central perylenediimide moiety as electron acceptor. The triad is extended at both ends by covalently bound siloxane chains that confer self organisation into thin smectic films at ambient temperature. When diluted in chloroform, selective excitation of the donor moiety leads to resonance energy transfer within 130 fs to the acceptor moiety, followed by the formation of a charge transfer (CT) state in ~3 ps. The CT state recombines entirely on a 55 ps time scale. In the liquid crystal films, excitonic intermolecular coupling leads to significant changes in the dynamics. Most remarkably, ultrafast intra- and intermolecular CT state formation occurs in about 60 fs, i.e. on a time scale comparable to electronic coherence times. While the intra-molecular CT states recombine on the same time scale as in solution or even faster, inter-molecular CT states live for about 1 ns. Last, triplet states of the perylenediimide moiety dominate the differential absorption after ~1 ns. We anticipate that the fast recombination of intra-molecular CT states and the triplet state formation may severely limit the photo-current in these materials. PMID- 22073403 TI - Determination of gas phase protein ion densities via ion mobility analysis with charge reduction. AB - We use a charge reduction electrospray (ESI) source and subsequent ion mobility analysis with a differential mobility analyzer (DMA, with detection via both a Faraday cage electrometer and a condensation particle counter) to infer the densities of single and multiprotein ions of cytochrome C, lysozyme, myoglobin, ovalbumin, and bovine serum albumin produced from non-denaturing (20 mM aqueous ammonium acetate) and denaturing (1 : 49.5 : 49.5, formic acid : methanol : water) ESI. Charge reduction is achieved through use of a Po-210 radioactive source, which generates roughly equal concentrations of positive and negative ions. Ions produced by the source collide with and reduce the charge on ESI generated drops, preventing Coulombic fissions, and unlike typical protein ESI, leading to gas-phase protein ions with +1 to +3 excess charges. Therefore, charge reduction serves to effectively mitigate any role that Coulombic stretching may play on the structure of the gas phase ions. Density inference is made via determination of the mobility diameter, and correspondingly the spherical equivalent protein volume. Through this approach it is found that for both non denaturing and denaturing ESI-generated ions, gas-phase protein ions are relatively compact, with average densities of 0.97 g cm(-3) and 0.86 g cm(-3), respectively. Ions from non-denaturing ESI are found to be slightly more compact than predicted from the protein crystal structures, suggesting that low charge state protein ions in the gas phase are slightly denser than their solution conformations. While a slight difference is detected between the ions produced with non-denaturing and denaturing ESI, the denatured ions are found to be much more dense than those examined previously by drift tube mobility analysis, in which charge reduction was not employed. This indicates that Coulombic stretching is typically what leads to non-compact ions in the gas-phase, and suggests that for gas phase measurements to be correlated to biomolecular structures in solution, low charge state ions should be analyzed. Further, to determine if different solution conditions give rise to ions of different structure, ions of similar charge state should be compared. Non-denatured protein ion densities are found to be in excellent agreement with non-denatured protein ion densities inferred from prior DMA and drift tube measurements made without charge reduction (all ions with densities in the 0.85-1.10 g cm(-3) range), showing that these ions are not strongly influenced by Coulombic stretching nor by analysis method. PMID- 22073404 TI - Excited-state proton-relay dynamics of 7-hydroxyquinoline controlled by solvent reorganization in room temperature ionic liquids. AB - The excited-state triple proton relay of 7-hydroxyquinoline (7HQ) along a hydrogen-bonded methanol chain in room temperature ionic liquids (RTILs) has been investigated using picosecond time-resolved fluorescence spectroscopy. The rate constant of the proton relay in a methanol-added RTIL is found to be slower by an order of magnitude than that in bulk methanol and to have unity in its kinetic isotope effect. These suggest that the excited-state tautomerization dynamics of 7HQ in methanol-added RTILs is mainly controlled by the solvent reorganization dynamics to form a cyclically hydrogen-bonded complex of 7HQ.(CH(3)OH)(2) upon absorption of a photon due to high viscosity values of RTILs. Because the cyclic complex of 7HQ.(CH(3)OH)(2) at the ground state is unstable in RTILs, the collision-induced slow formation of the cyclic complex should take place upon excitation prior to undergoing subsequent intrinsic proton transfer rapidly. PMID- 22073405 TI - Watching over baby: expectant parenthood and the duty to be well. AB - In contemporary Western society, individuals are encouraged to adopt a "duty to be well ideology" by assuming personal responsibility for health through engagement in self-care practices. We explored the duty to be well within the contexts of pregnancy, first-time parenthood, and marriage. Analyses were informed by Foucault's work on surveillance. In-depth interviews were conducted during the 7th or 8th month of pregnancy with 14 married couples expecting their first child. The sample was recruited from two U.S. university towns. Participants conceptualized the duty to be well as the expectant mother's unyielding bodily obligation to her unborn child and the notion that she should engage in bodily routines to shape fetal development. Both wives and husbands participated in the duty to be well, which included three dimensions: the need to feed, the need to take physical care/stay out of harm's way, and the need to thwart maternal anxiety. However, findings indicated that efforts to safeguard unborn children were sometimes a slippery slope, representing an uneven path and/or inciting ambivalence. Further, participants experienced surveillance associated with the duty to be well as both caring and controlling, depending upon the context of the surveillance and the perceived meaning of the monitoring. PMID- 22073406 TI - It's not only for the money: an analysis of adolescent versus adult entry into street prostitution. AB - Numerous studies examine the causal factors of entrance into prostitution and find economic marginalization, substance addiction, and interpersonal networks are common reasons women enter the trade. However, we know less about the role that age of onset plays in shaping female pathways into prostitution. Here, we build from insights into previous research by analyzing not only entry pathways but also how age categories are linked to time spent in the trade and whether the length of time in prostitution exacts a greater "toll" on women. Drawing from the feminist and age of onset literatures, we analyze 40 in-depth interviews with female street prostitutes from five U.S. cities. Our results underscore the importance of age as an organizing feature of women's pathways into prostitution and the potential associated consequences of working in this trade. PMID- 22073407 TI - Racetalk and sport: the color consciousness of contemporary discourse on basketball. AB - This article explores how a sample of college students discursively negotiated perceptions of race and ability in the context of mediated sport. A majority of respondents expressed acceptance of a link between racial identity and sport specific skills. However, rather than articulate this notion overtly and directly, rhetorical strategies, such as disclaimers and coded language, were used. We analyze these responses as a form of "racetalk" (Bonilla-Silva and Forman 2000) to more specifically unpack the significance of discourse within the post-Civil Rights Movement era. Although the language used to discuss race in this sample, like the contemporary era more generally, appears colorblind and progressive on the surface, it is undergirded by a distinct form of color consciousness. PMID- 22073408 TI - The potato's contribution to population and urbanization: evidence from a historical experiment. AB - We exploit regional variation in suitability for cultivating potatoes, together with time variation arising from their introduction to the Old World from the Americas, to estimate the impact of potatoes on Old World population and urbanization. Our results show that the introduction of the potato was responsible for a significant portion of the increase in population and urbanization observed during the eighteenth and nineteenth centuries. According to our most conservative estimates, the introduction of the potato accounts for approximately one-quarter of the growth in Old World population and urbanization between 1700 and 1900. Additional evidence from within-country comparisons of city populations and adult heights also confirms the cross-country findings. PMID- 22073409 TI - Identity, morals, and taboos: beliefs as assets. AB - We develop a theory of moral behavior, individual and collective, based on a general model of identity in which people care about "who they are" and infer their own values from past choices. The model sheds light on many empirical puzzles inconsistent with earlier approaches. Identity investments respond nonmonotonically to acts or threats, and taboos on mere thoughts arise to protect beliefs about the "priceless" value of certain social assets. High endowments trigger escalating commitment and a treadmill effect, while competing identities can cause dysfunctional capital destruction. Social interactions induce both social and antisocial norms of contribution, sustained by respectively shunning free riders or do-gooders. PMID- 22073410 TI - Exploring patterns of movement suspension in pedestrian mobility. AB - One of the main tasks in analyzing pedestrian movement is to detect places where pedestrians stop, as those places usually are associated with specific human activities, and they can allow us to understand pedestrian movement behavior. Very few approaches have been proposed to detect the locations of stops in positioning data sets, and they often are based on selecting the location of candidate stops as well as potential spatial and temporal thresholds according to different application requirements. However, these approaches are not suitable for analyzing the slow movement of pedestrians where the inaccuracy of a nondifferential global positioning system commonly used for movement tracking is so significant that it can hinder the selection of adequate thresholds. In this article, we propose an exploratory statistical approach to detect patterns of movement suspension using a local indicator of spatial association (LISA) in a vector space representation. Two different positioning data sets are used to evaluate our approach in terms of exploring movement suspension patterns that can be related to different landscapes: players of an urban outdoor mobile game and visitors of a natural park. The results of both experiments show that patterns of movement suspension were located at places such as checkpoints in the game and different attractions and facilities in the park. Based on these results, we conclude that using LISA is a reliable approach for exploring movement suspension patterns that represent the places where the movement of pedestrians is temporally suspended by physical restrictions (e.g., checkpoints of a mobile game and the route choosing points of a park). PMID- 22073411 TI - Endotoxin exposure in textile workers, tetrachloroethylene in dry cleaners. PMID- 22073412 TI - Localised convulsions from tumour of the brain. By J. Hughlings Jackson MD FRS, physician to the Hospital for the Epileptic and Paralysed, and to the London Hospital. Brain 1882; 5: 364-74; with On temporary paralysis after epileptiform and epileptic seizures; a contribution to the study of dissolution of the nervous system. By J. Hughlings Jackson MD FRCP FRS. Brain 1881; 4: 433-51; with A contribution to the comparative study of convulsions. By J. Hughlings Jackson, MD FRCP FRS. Brain 1886; 9: 1-23. PMID- 22073414 TI - Leukemic transformation of anaplastic large-cell lymphoma. PMID- 22073415 TI - Distal metadiaphyseal tibial fractures. PMID- 22073416 TI - A year of hope and heartache: on the road with hospice. PMID- 22073417 TI - Late bloomers & baby boomers: success in the second act of life. PMID- 22073425 TI - Estimating the effects of cigarette taxes on birth outcomes. AB - Employing provincial data from 1979 to 2004 allows us to exploit the significant (45 percent to 60 percent) reduction in excise taxes in Eastern Canada enacted in February 1994 to estimate the impacts of cigarette taxes on birth outcomes. Empirical estimates suggest that an increase in cigarette taxes is significantly associated with lower infant mortalities. However, we also find some evidence of a counter-intuitive positive correlation between taxes and fetal deaths. Overall, conditional on methodology, we find increased lagged per capita health expenditures and the number of physicians to be significantly associated with improvements in birth outcomes. PMID- 22073426 TI - We fall down: the African American experience of coping with the homicide of a loved one. AB - Rates of homicide among African Americans are much higher than those of other racial or ethnic groups. Research has demonstrated that homicide can be psychologically debilitating for surviving family members. Yet, exploring the experiences of homicide victims' surviving loved ones has received little attention. This study examined the coping strategies of African American survivors of homicide. Qualitative interviews were conducted with 8 African American family members (ages 18-82) of homicide victims. Survivors were recruited from the Massachusetts Office of Victim Services and from homicide survivor support, school, and community groups throughout the New England area. Interviews were conducted using open-ended questions derived from coping, support network, grief, and bereavement literatures. Results indicate that the primary coping strategies utilized by African American survivors of homicide victims are spiritual coping and meaning making, maintaining a connection to the deceased, collective coping and caring for others, and concealment. Implications for research and practice are discussed. PMID- 22073427 TI - Disordered eating in African American and Caucasian women: the role of ethnic identity. AB - The influential roles of culture and ethnic identity are frequently cited in developing disordered eating and body dissatisfaction, constituting both protective and risk factors. For African American women, strongly identifying with African American cultural beauty ideals may protect against disordered eating to lose weight, but may actually increase risk in development of disordered eating directed at weight gain, such as binge eating. This study compares African American and Caucasian women on disordered eating measures, positing that African American women show greater risk for binge eating due to the impact of ethnic identity on body dissatisfaction. Findings indicate low levels of ethnic identity represent a risk factor for African American women, increasing the likelihood of showing greater binge eating and bulimic pathology. In Caucasian women, high levels of ethnic identity constitute a risk factor, leading to higher levels of both binge eating and global eating pathology. Implications for prevention and treatment are discussed. PMID- 22073428 TI - Non-exercise physical activity in agricultural and urban people. AB - With evidence that urbanisation is associated with obesity, diabetes, hypertension and cardiovascular disease, this article compares daily physical activity between rural and urban dwellers. Specifically, it examines habitual daily activity levels, non-exercise activity thermogenesis (NEAT) and energy expenditure in agricultural and urban Jamaicans and urban North Americans. Ambulation was 60 per cent greater in rural Jamaicans than in the urban dwellers (4675 +/- 2261 versus 2940 +/- 1120 ambulation-attributed arbitrary units (AU)/day; P = 0.001). Levels of ambulation in lean urban Jamaicans were similar to those in lean urban North Americans, whereas obese urban dwellers walked less than their lean urban counterparts (2198 +/- 516 versus 2793 +/- 774 AU/day; P = 0.01). The data with respect to daily sitting mirrored the walking data; obese Americans sat for almost four hours more each day than rural Jamaicans (562 +/- 78 versus 336 +/- 68 minutes/day; P < 0.001). Urbanisation is associated with low levels of daily activity and NEAT. PMID- 22073429 TI - Assessing women's understandings of health in rural Papua New Guinea: implications for health policy and practice. AB - In Papua New Guinea (PNG), women's health is addressed by applying biomedical solutions which often ignore the complexity of women's histories, cultural contexts and lived experiences. The objective of this study was to examine adult and older women's perceptions of health and well-being to identify priority areas for public service interventions. Rapid ethnographic assessment was conducted in the Wosera district, a rural area of PNG from mid-2005 to early 2006, to examine the health concerns of women. Twenty-seven adult women and 10 older women participated in the study. Health was not limited to one aspect of a woman's life, such as their biology or maternal roles; it was also connected with the social, cultural and spiritual dimensions of women's daily existence. Participants also identified access to money and supportive interpersonal relationships as significant for good health. A disconnect was found to exist between women's understandings of good health and socio-political health policies in PNG, something likely to be repeated in health service delivery to different cultural groups across the Asia Pacific region. Health and development practitioners in PNG must become responsive to the complexity of women's social relationships and to issues relating to the context of women's empowerment in their programmes. PMID- 22073430 TI - Decentralization, democratization, and health: the Philippine experiment. AB - In 1991, the Philippines joined a growing list of countries that reformed health planning through decentralization. Reformers viewed decentralization as a tool that would solve multiple problems, leading to more meaningful democracy and more effective health planning. Today, nearly two decades after the passage of decentralization legislation, questions about the effectiveness of the reforms persist. Inadequate financing, inequity, and a lack of meaningful participation remain challenges, in many ways mirroring broader weaknesses of Philippine democracy. These concerns pose questions regarding the nature of contemporary decentralization, democratization, and health planning and whether these three strategies are indeed mutually enforcing. PMID- 22073431 TI - Images of welfare in law and society: the British welfare state in comparative perspective. AB - Designed by Beveridge and built by Attlee's post-war Labour government, the welfare state was created during the 1940s. Britain has been seen - in domestic debates and internationally - as a world first: the place where both the idea and the practice of the welfare state were invented. I draw together comparative welfare state analysis with law and society scholarship (previously largely developed in isolation from one another) - as well as using British political cartoons as a source - to develop a revisionist historical critique of this conventional wisdom. First, the British welfare state has always been comparatively parsimonious. Second, the idea of the welfare state seems to have its origins outside the United Kingdom and this terminology was adopted relatively late and with some ambivalence in public debate and scholarly analysis. Third, a large body of socio-legal scholarship shows that robust 'welfare rights' were never embedded in the British 'welfare state'. PMID- 22073432 TI - iPods, viagra, and the praiseworthy life: epideictic rhetoric in technology and medical print advertising. PMID- 22073433 TI - Working women households and time-saving consumption: empirical evidence from Kerala. AB - This article explores the impact of labour force participation of Indian women on the consumption expenditure of their households. Field survey data were collected from working-wife and non-working wife households in Kerala, the state in India with the highest labour market participation of women in the organised sector. Differences in time-saving consumption expenditures of working and non-working wife households and different variables influencing consumption expenditures were researched. The study shows that among the variables which positively affect the time-saving consumption expenditure of the households, non-economic factors influence the time-saving consumption expenditure of the working-wife households more prominently than in non-working wife households. PMID- 22073434 TI - Medical science and the military: the Allies' use of amphetamine during World War II. AB - Although amphetamine was thoroughly tested by leading scientists for its effects in boosting or maintaining physical and mental performance in fatigued subjects, the results never provided solid grounds for approving the drug's use, and, in any case, came too late to be decisive. The grounds on which amphetamine was actually adopted by both British and American militaries had less to do with the science of fatigue than with the drug's mood-altering effects, as judged by military men. It increased confidence and aggression, and elevated "morale." PMID- 22073435 TI - Women's fashions in transition: Ottoman borderlands and the Anglo-Ottoman exchange of costumes. AB - Following the considerable increase in the interactions between Ottomans and Europeans, Ottoman port cities, referred to here as "borderlands," became meeting places of distinct worlds. Ottoman and British people met, clashed, and grappled with each other in the borderlands of the Ottoman Empire. There was unbalanced, disparate, and disproportionate, but also mutual and constant interchange between the two societies. This article discusses one facet of this interchange: the Anglo-Ottoman exchange of women's costumes. PMID- 22073436 TI - The "swinish multitude": controversies over hogs in antebellum New York City. AB - In the first half of the nineteenth century, New Yorkers fought passionately over the presence of hogs on their streets and in their city. New York's filthy streets had cultivated an informal economy and a fertile environment for roaming creatures. The battles-both physical and legal-reveal a city rife with class tensions. After decades of arguments, riots, and petitions, cholera and the fear of other public health crises ultimately spelled the end for New York's hogs. New York struggled during this period to improve municipal services while adapting to a changing economy and rapid population growth. The fights between those for and against hogs shaped New York City's landscape and resulted in new rules for using public space a new place for nature in the city. PMID- 22073437 TI - Unsightly urban menaces and the rescaling of residential segregation in the United States. AB - In this article, the author uses a slum clearance project in Lexington, Kentucky, as a lens through which to examine the spatial dynamics of racial residential segregation during the first half of the twentieth century. At the time, urban migration and upward socioeconomic mobility on the part of African Americans destabilized extant residential segregation patterns. Amid this instability, various spatial practices were employed in the interest of maintaining white social and economic supremacy. The author argues that such practices were indicative of a thoroughgoing reinvention of urban socio-spatial order that in turn precipitated the vastly expanded scale of residential segregation still found in U.S. cities today. Evidence of this reinvented ordering of urban space lies in the rendering of some long-standing African American neighborhoods as "out of place" within it and the use of slum clearance to remove the "menace" such neighborhoods posed to it. PMID- 22073438 TI - "Ready to shoot and do shoot": black working-class self-defense and community politics in Harlem, New York, during the 1920s. AB - Throughout the first three decades of the twentieth century, black people in New York City encountered white violence, especially police brutality in Manhattan. The black community used various strategies to curtail white mob violence and police brutality, one of which was self-defense. This article examines blacks' response to violence, specifically the debate concerning police brutality and self-defense in Harlem during the 1920s. While historians have examined race riots, blacks' everyday encounters with police violence in the North have received inadequate treatment. By approaching everyday violence and black responses-self-defense, legal redress, and journalists' remonstrations-as a process of political development, this article argues that the systematic violence perpetrated by the police both mobilized and politicized blacks individually and collectively to defend their community, but also contributed to a community consciousness that established police brutality as a legitimate issue for black protest. PMID- 22073439 TI - Women's employment and changing gender relations in Puerto Rico. AB - This article discusses Helen Safa's analyses of the impact of development strategies and social policies on gender relations and women headed families in the Caribbean and Puerto Rico. The discussion focuses on findings of a research project regarding patterns of women's employment, autonomy, marital relations, family headship and poverty in Puerto Rico in the decade beginning in the year 2000, using excerpts from interviews conducted with women workers displaced from a clothing and a tuna factory between 2001 and 2002 (Colon et al. 2008), as well as data from the Public Use Sample (PUMS) of the U.S. Census Puerto Rico Community Survey 2005-2007. It is argued that women's employment has resulted in advances in women's autonomy, gender equity, and renegotiations of the provider role, but, intensified by men's unstable earnings, it has also led to the increase of female family headship even among married women. Women's education and employment have been an important means of reducing family poverty both among dual earner families and female heads. Yet, the continuing joblessness in the Island places even higher educated sectors on the verge of economic precariousness. PMID- 22073440 TI - Sex and sentiment in Cuban tourism. AB - Helen Safa has been a leading program builder and pioneer in research that examines the complex intersections of gender, race, class, and nation in Latin America and the Caribbean. Her comparative research culminated in her influential book, The Myth of the Male Breadwinner: Women and Industrialization in the Caribbean (1995), which examined gender, family, and employment across three Caribbean societies. Over several decades Safa has inspired scholarship throughout the Caribbean and the Americas and her work is exemplary of engaged anthropology in the region. Here I present work I conducted in Cuba that was guided, like my work in Peru, Nicaragua, and southern Mexico by the writings of Safa and others who saw the critical need to bring gender into meaningful discussion in the field of Latin American and Caribbean studies. In what follows, drawn from my broader research on tourism in four nations, I explore and reflect on the contemporary dynamics of sex and romance tourism in Cuba. I suggest that the allure of this domain of tourism may be enhanced by Cuba's global political identity, and that Cuban women participating in commodified and intimate exchanges reveal an ability to get along in a market economy that generally excludes them. PMID- 22073441 TI - Anthropology in a postcolonial colony: Helen I. Safa's contribution to Puerto Rican ethnography. AB - This article assesses Helen I. Safa's legacy to anthropological thought in Puerto Rico. The first part of the article locates Safa's research on the Island within a long tradition of fieldwork by U.S. scholars since the early twentieth century. More recent research, conducted mostly by Puerto Rican women anthropologists and other social scientists, has expanded upon Safa's insights on gender and work. The second part of the essay analyzes Safa's major empirical work, The Urban Poor of Puerto Rico: A Study in Development and Inequality. Above all, this book helped overcome the theoretical impasse over the culture of poverty that characterized much of urban anthropology during the 1960s and 1970s. The article concludes with an appraisal of the relevance of Safa's work for the ethnography of contemporary Puerto Rico. PMID- 22073442 TI - Drawing cure: children's drawings as a psychoanalytic instrument. AB - This essay deals with the special case of drawings as psychoanalytical instruments. It aims at a theoretical understanding of the specific contribution made by children's drawings as a medium of the psychical. In the influential play technique developed by Melanie Klein, drawing continuously interacts with other symptomatic (play) actions. Nonetheless, specific functions of drawing within the play technique can be identified. The essay will discuss four crucial aspects in depth: 1) the strengthening of the analysis's recursivity associated with the graphic artifact; 2) the opening of the analytic process facilitated by drawing; 3) the creation of a genuinely graphic mode of producing meaning that allows the child to develop a "theory" of the workings of his own psychic apparatus; and 4) the new possibilities of symbolization associated with the latter. In contrast to classical definitions of the psychological instrument, the child's drawing is a weakly structured tool that does not serve to reproduce psychic processes in an artificial, controlled setting. The introduction of drawing into the psychoanalytic cure is by no means interested in replaying past events, but in producing events suited to effecting a transformation of the synchronic structures of the unconscious. PMID- 22073443 TI - Mexicanas en guerra: World War II and the discourse of Mexican female identity. PMID- 22073445 TI - Festschrift for Eugene B. Brody, MD. PMID- 22073444 TI - Reporting on the Holocaust: the view from Jim Crow Alabama. AB - The press in Alabama covered major events taking place in Germany from the rise of Adolf Hitler and the Nazis in 1933 through the Nuremberg Trials in 1946. Journalists in the state provided extensive coverage, and editors did not hesitate to opine on the persecution of the Jews in Europe. Yet, Alabama's white run press failed in the end to explain the events as a singularly Jewish tragedy. The state's black-run press, for its part, used the news of the mass killings of the Jews to warn against the dangers of conceptions of racial superiority-a primary concern for black southerners living in the Jim Crow South. PMID- 22073446 TI - Proceedings of HVDA-2010, the 6th International Symposium on Hormone and Veterinary Drug Residue Analysis. June 1-4, 2010. Gent, Belgium. PMID- 22073447 TI - Proceedings of the Annual Meeting of the Norwegian Neurological Association. November 2010. Oslo, Norway. PMID- 22073448 TI - Proceedings of the XVIIIth IAAP (International Association for Analytical Psychology) Congress. Montreal, Canada. August 22-27, 2010. PMID- 22073449 TI - A look back as we move forward. PMID- 22073450 TI - [Law enforcement in Polish towns and cities and Polish society in the 14th 16th centuries]. PMID- 22073451 TI - [Manifestations of the Romantic 'taedium vitae:' suicides in Polish territories in the years 1815-30]. PMID- 22073452 TI - "One large secure, solid background": Melanie Klein and the origins of the British welfare state. PMID- 22073453 TI - [A case study of child brides during the mid-Qing dynasty]. PMID- 22073454 TI - The discovery of the child as an object 'sui generis' of cure and research by Melanie Klein as reflected in the notes of her first child analyses in Berlin, 1921-1926. PMID- 22073455 TI - Clinical use of lasers in caries diagnosis and therapy. AB - Laser technology is now ubiquitous in science, business, the arts, the military, industry, telecommunications, entertainment and medicine. It is increasingly finding a useful place in dentistry to offer the potential for practical solutions to managing difficult clinical problems. Research into the clinical use of lasers in diagnostic and therapeutic dental procedures has escalated rapidly in recent years. Laser technology has revolutionized the treatment of dental caries. This article reviews the role of laser technology in the clinical management of caries, early caries diagnosis and treatment planning decision making, caries prevention, soft tissue management, fluorescence aided caries elimination and fluorescence feedback-controlled selective caries removal. Laser technology plays a vital role in enhancing caries diagnosis and therapy. PMID- 22073456 TI - Clinical evaluation of ceramic implant abutments in anterior restorations. AB - The development of new high strength ceramic abutments can enhance the overall aesthetic outcome of an implant-supported prosthesis. This study was to compare the clinical application of alumina and zirconia ceramic implant abutments in the anterior region. Twenty-three consecutive patients requiring single-tooth implants in the anterior region were randomized to receive either an alumina ceramic abutment (CeraAdapt) or a zirconia ceramic abutment. All-ceramic (IPS Empress 2) crowns were then fabricated and cemented over the abutments with composite cement. Peri-implant mucosal health and bone levels were evaluated by the gingival index and radiographs at 2-week and 1-year follow-up. Aesthetic outcomes as well as technical problems with the restorations were evaluated during the observation period from 12 to 48 months after functional loading. A total of 17 alumina ceramic abutments and 18 zirconia ceramic abutments were evaluated. No patients dropped out during the study period. Eighteen out of the 23 patients maintained good function throughout the study. The median observation period was 21 months. Ceramic crown loosening was found in two restorations at 1 week and 2-years respectively after insertion. One ceramic crown fractured at 1 week after insertion. At 1-year follow-up, mean marginal bone loss around implants was 1.2 +/- 0.5 mm and the peri-implant mucosa in relation to abutment or crown was healthy with a mean gingival score of 0.6 +/- 0.2. All patients were satisfied with the final aesthetic outcome. However, two alumina abutments fractured after two years of loading. In conclusion, both ceramic abutments have shown a favourable biological response and aesthetic outcome; however, zirconia abutments with their superior mechanical properties might be better for supporting single-tooth implant restorations in the aesthetic zone. PMID- 22073457 TI - Contemporary concepts in the management of failed full arch restorations. PMID- 22073458 TI - Dental caries: where to from here? PMID- 22073459 TI - Three dimensional distraction osteogenesis of the midface: orthodontic considerations. AB - Three-dimensional Le Fort I DO can be used to selectively widen, lengthen, and vertically reposition the maxilla, without bone grafts and with a good adaptation of the surrounding soft tissues. Therefore DO is a complementary tool for conventional orthodontics and orthognathic surgical techniques that address maxillary deficiency. It is the technique of choice for patients who require significant maxillary repositioning and have significant soft tissue limitations, such as scarring secondary to previous surgical procedures. The procedure can be performed in children prior to reaching skeletal maturity and also in adult patients. Finally, three-dimensional maxillary reconstruction by distraction of the Le Fort I segment offers an improved aesthetic outcome and less risk of deterioration of speech in comparison with traditional orthognathic techniques. PMID- 22073460 TI - Intracanal instrumentation and disinfection. AB - Proper root canal instrumentation and disinfection are key objectives in endodontic therapy. This paper discusses the current concepts of root canal instrumentation from a biological and mechanical perspective including the need for an intracanal medication. PMID- 22073461 TI - An update on periodontal aetiopathogenesis and clinical implications. AB - Periodontal disease is the most commonly occurring yet unusual infection in humans. It is initiated by pathogenic plaque biofilm and characterized by bacteria-induced inflammatory destruction of tooth-supporting structures and alveolar bone. Periodontitis remains the most common cause of tooth loss in adults. Currently, periodontal diseases are also recognized as serious infections with profound effects on general health. In recent years, new concepts and discoveries have been made in further understanding of the nature of periodontal disease and its aetiopathogenesis. These can be well reflected in recognition of dental plaque as a biofilm; identification and characterization of periodontopathogens and their virulence factors; recognition of the importance of host-microbe symbiosis in periodontal health; identification of novel innate host defence molecules in periodontal tissues; further understanding of the molecular mechanisms involved in tissue destruction and alveolar bone resorption; appreciation of the crucial role of host susceptibility in periodontal pathogenesis; and identification of risk factors and incorporation of risk assessment in clinical practice. Committed oral health care professionals should therefore keep abreast of these changing concepts in periodontology and updated strategies for appropriate evidence-based practice. These views are fundamentally important for prevention, diagnosis and treatment of periodontal diseases and peri-implant infections, as well as for long-term maintenance of periodontal health and implant stability. This paper updates the advances in aetiopathogenesis of periodontal disease and highlights the relevant clinical implications and future perspectives. PMID- 22073462 TI - Health behaviour, metabolic control and periodontal status in medically treated Chinese with type 2 diabetes mellitus. AB - OBJECTIVE: Relationships between demographic, health behaviour and diabetes mellitus (DM) parameters and periodontal status were assessed among a group of nonsmoking, low-income, middle-aged to elderly medically treated Hong Kong Chinese subjects with type 2 diabetes mellitus (DM). MATERIALS AND METHODS: 193 Chinese, dentate, type 2 DM patients (56.5 +/- 9.0 years; recorded DM duration 7.0 +/- 5.2 years) attending a charity hospital specialist clinic were surveyed. Subject demography, periodontal status, Body Mass Index (BMI), DM control, serum TNF-alpha level and general health behaviour (GHB) were recorded. RESULTS: Periodontitis was prevalent (80.3% of subjects with PPD > or = 5 mm and 65.8% subjects with full-mouth mean PAL > 3.0 mm). Mean HbA1c, fasting plasma glucose and BMI were 7.6 +/- 1.6%, 8.2 +/- 2.9 mmol/L and 25.4 +/- 3.7 kg/m2 respectively. Serum TNF-alpha level was similar to the reported Chinese population norm. Full-mouth mean clinical attachment level was associated with DM duration while full-mouth mean probing pocket depth was associated with GHB (p < 0.05). The Gingival Index, was greater in men, and associated with higher HbA1c% and lower education attainment (p < 0.03). CONCLUSION: In this group of non smoking, predominantly low-education background, overweight, Chinese subjects with fairly well-controlled type 2 DM, periodontal attachment loss and periodontal disease appeared to be associated with DM duration and health behaviour. Health care providers should consider paying more attention to improving the GHB of their type 2 DM patients with long DM duration. DM subjects with a low educational background, having higher HbA1c% and males are more likely to experience gingival inflammation. PMID- 22073463 TI - New approaches in parotid gland surgery. AB - Various skin incision for access to the parotid region are described by different authors, which differ in extension and localization of the scar. Therefore after parotidectomy, patients are often left with a retromandibular and cervical depression. Maintaining normal facial contour may be difficult in parotidectomy defects, but a good symmetry can and should be achieved when reconstructing the parotid region with a specific approach. The authors show their experience in parotid gland surgery using a new skin incision to improve the aesthetic and functional results and three different techniques the reconstruction of the parotid region. PMID- 22073464 TI - Maxillary and mandibular distraction osteogenesis in growing patients: lessons learned after 14 years and update on indications. AB - In the past decade, distraction osteogenesis (DO) has become increasingly popular and has opened new therapeutic perspectives for the treatment of numerous congenital and acquired craniofacial skeletal anomalies. However, DO mechanisms still remain unclear and different treatment protocols are applied by different groups. Here the authors use their 14 years-clinical experience to evaluate DO parameters such as maxillary and mandibular DO stability over time, especially in growing patients, DO effects on soft tissues and the correlation between the bone gain and lengthening capabilities of the device. Based on these data, clinical indications and treatment protocols for mandibular and maxillary DO are suggested. The application of DO to the membranous bones of the craniofacial skeleton has opened a new chapter in the surgical treatment of several congenital and acquired craniofacial deformities. Based on this experience, the authors recommend DO indications guidelines in selected cases of hemifacial microsomia, maxillary hypoplasia and narrow mandible with anterior dental crowding. PMID- 22073465 TI - Distraction osteogenesis: role and clinical applications in the maxillofacial region. AB - Distraction osteogenesis or callostasis is a technique of new bone formation by gradual separation of bony fragments. The method was first developed for limb lengthening but recently this process was widely applied to the cranio maxillofacial bones. The application included unlimited bone lengthening and reconstruction of segmental defects. Several designs of extra-oral and intra-oral distraction devices were invented to suit different areas of craniofacial bone. Nevertheless intraoral distractors have several advantages including minimal scarring and being less cumbersome. Clinical cases using distraction osteogenesis as an alternative treatment to conventional surgical procedures for maxillo mandibular lengthening and reconstruction of alveolar segmental defects after tumour resection before implant installation are presented and discussed. PMID- 22073466 TI - Distraction or orthognathic surgery for cleft lip and palate patients: which is better? AB - Maxillary deformities of cleft lip and palate (CLP) can be treated by either conventional osteotomies (CO) or distraction osteogenesis (DO). Which one is better for CLP patients suffering from a moderate extent of maxillary hypoplasia? The aim of the study was to evaluate the treatment outcomes of CO and compared with DO in correction of moderate maxillary hypoplasia. The results showed that CLP patients receiving DO were more anxious and depressed during the first three months but became happier in the long-term. The nasalance of DO and CO was found to be similar. However, on the skeletal stability, DO was shown to be significantly more stable when compared with CO in the horizontal plane within the first six months and in vertical plane during the first three months and between 1-2 year. PMID- 22073467 TI - Management of sinus surgery complications. PMID- 22073468 TI - Back and neck care. AB - Musculoskeletal disorders account for 29.5% of early retirement among dentists. Most work-related musculoskeletal disorders in Dentistry are spinal. Non-specific and insidious gradual onset injuries such as prolonged tension and pressure on muscles, tendons, ligaments, joints and discs in poor posture or alignment account for more than 80% of commonly seen musculoskeletal disorders that are often regarded as work-related and repetitive strain injuries, arthritis and degeneration. Work performance and activities of daily living could be severely affected. The source and cause of injuries should be tackled head on with specific but simple self-management programme including understanding of the cause of symptoms, postural correction and specific exercises. PMID- 22073469 TI - Anodization increases early integration of Osstem implants in sheep femurs. AB - BACKGROUND: Spark discharge anodic oxidation forms a porous TiO2 film on the surface of titanium oral implants, increasing surface roughness and concentrations of calcium and phosphate ions. In this study, anodic-treated oral implants were placed in an animal model and analysed using clinical, micro computerized tomographic (micro-CT) and histometric techniques. METHODS: Pairs of 3.5 mm x 8.5 mm long titanium implants (Osstem Implant Co., Ltd. Seoul, Korea), with blasted (control) or blasted and oxidized surfaces (test), were placed into the right femoral condyles of 10 sheep. Animals were sacrificed after 1 month unloaded healing. Resonant frequency analysis (RFA) was measured in implant stability quotient (ISQ) using the Mentor II device. Specimens were scanned using medium resolution micro-CT (Skyscan 1172). Mean percent bone-to-implant contact (%BIC) was calculated from two images per implant by three different operators, using Image J software. Inter- and intra-examiner differences were calculated. Specimens were then embedded in methacrylate and undemineralized ground sections were digitized. Mean %BIC was measured using Image J at x 20 magnification for the best-three consecutive threads from the most central section. RESULTS: Mean micro-CT %BIC was similar for control and test (57.2 +/- 0.05% versus 56.4 +/- 0.03%, p = 0.5). There was considerable inter-examiner variability (interclass correlation coefficient = 0.44). RFA showed no clinically-detectable difference between the two groups (control ISQ: 75.2 +/- 4.2; test ISQ: 76.3 +/- 1.7; p = 0.48). However, histometric analysis found a marked and highly statistically significant difference (%BIC Test 72.5 +/- 8.6%, Control 46.2 +/- 12.1%, p = 0.01). CONCLUSIONS: The novel anodic oxidation technique increased early ossointegration of rough-surfaced implants by 157%. Neither clinical testing with resonant frequency analysis nor radiographic analysis using micro-CT had sufficient resolution to detect this improvement. Whether this gain in early bone implant contact is clinically significant in the context of early occlusal loading is the subject of subsequent experiments. PMID- 22073470 TI - Inhibitory effect of quercetin on periodontal pathogens. AB - INTRODUCTION: Periodontal disease and associated bone loss can severely hinder orthodontic treatment. Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are bacteria which are strongly associated with this type of bone loss. Quercetin, a unique flavonoid, which is found in many common foods including apples, onions and tea may have a effect against these bacteria. AIMS: To study the effect of quercetin on the in vitro growth of periodontal pathogens Aa and Pg. MATERIAL AND METHODS: The antimicrobial effects were determined in vitro using a broth dilution assay. Aa and Pg were grown to a density of 10(7) to 10(8) cfu/mL and subsequently incubated with test solutions of quercetin at different concentrations (0.025 g/mL, 0.05 g/mL, and 0.1 g/ mL). 0.2% chlorhexidine was used as the positive control and 0.9% sodium chloride (NaCl) as the negative control. Aliquots for the growth assay were taken as soon as the solutions were mixed, and after 1, 3, 6, and 24 hours of incubation in an anaerobic chamber for Aa and Pg. Colonies appearing on the blood agar plates were visually counted after three days for Aa and 5 days for Pg. RESULTS: This study demonstrated that quercetin is a potent antimicrobial agent. When Aa and Pg were incubated with quercetin, their growth began to be inhibited at 1 hour. Aa, shows a transient inhibitory effect for 1 to 12 hours after which the antimicrobial effect gradually decreasds. With Pg, the effect increased with time and complete inhibition was achieved with concentrations of 0.1 g/mL, 0.05 g/mL and 0.025 g/mL by 24 hours. No significant difference was found between the chlorhexidine group and the quercetin solution after 24 hours of incubation. CONCLUSION: Quercetin has an inhibitory effect on Aa and Pg. PMID- 22073471 TI - Sinus lifting: new protocols with nanotechnological implant surfaces. PMID- 22073472 TI - Special needs dentistry: the next ten years. AB - There is no doubt that in special needs dentistry, Australasia is one of the major global players. There is now an accepted scope of practice, accredited training programs and specialists registered with their local dental boards. These early achievements reflect the tremendous input provided by the primary stakeholders, such as the Royal Australasian College of Dental Surgeons. But the honeymoon is now over. Where will Special Needs Dentistry be in ten years? This paper discusses the journey so far and where the discipline will be heading. PMID- 22073473 TI - Evidence-based management of dental injury: case presentations. PMID- 22073474 TI - Effect of Danshen extract on bone formation. AB - BACKGROUND: Danshen is a traditional Chinese medicine used for treatment of cardiac diseases through improving blood circulation. The authors' laboratory compared the amount of new bone formed in collagen matrix with Danshen extract with that produced by bone graft and collagen matrix alone. METHODS: Eighteen bone defects, 5 mm x 10 mm were created in the parietal bone of nine New Zealand White rabbits. In the experimental group, six defects were grafted with a collagen matrix with Danshen extract. In the control groups, six defects were grafted with collagen matrix alone (active control) and six were left empty (passive control). The animals were killed on day 14 and the defects were dissected and prepared for histological assessment. Serial sections were cut across each defect. Quantitative analysis of new bone formation was made on 100 sections (50 sections for each group) using image analysis. RESULTS: A total of five times more new bone was present in defects grafted with Danshen extract in a collagen matrix than those grafted with collagen matrix alone. Very little new bone was formed in the passive control group. CONCLUSIONS: Danshen extract in collagen matrix has the effect of increasing new bone formation locally and can be used for bone grafting especially in cases with compromised vascular responses. PMID- 22073475 TI - Bacteraemia due to flossing: a cohort study. PMID- 22073476 TI - A comparison of pain experienced by patients treated with labial and lingual orthodontic appliances. AB - There has been a paradigm shift within orthodontics in the use of lingual fixed appliances compared with the use of labial fixed appliances on the basis of perceived benefits and acceptance by patients. METHODS: A matched case-control prospective longitudinal study of adult patients treated in the Orthodontic Department, Prince Philip Dental Hospital, Hong Kong. Group A consisted of 30 patients treated with lingual orthodontic appliances. Group B consisted of 30 patients treated with labial orthodontic appliances. Data were collected at five different time points using questionnaire: pre-treatment; one week after the placement of the fixed appliance, and then at 1-month, 3-months, and 6-months thereafter. The questionnaire consisted of 15 items, in which 11 items were rated on a visual analogue scale. RESULTS: Patients' experience of pain decreased over the study period (p < 0.001); Those treated with lingual appliances reported significantly greater pain experience than those treated with labial appliances with respect to tongue pain (p < 0.001). However, those treated with labial appliances reported experiencing significantly more lip pain (p < 0.01), cheek pain (p < 0.001), and gum pain (p < 0.05). Patients treated with lingual appliances reported experiencing pain earlier on than those treated with labial appliances (p < 0.05). Both groups reported the pain level to be the same throughout the day (p > 0.05). There was no significant difference in reported disturbance of sleep or analgesic consumption between the two groups (p > 0.05). CONCLUSION: Patients treated with both labial and lingual orthodontic appliances experienced pain during treatment, but this decreased over the treatment period. Patients treated with lingual appliances experienced more tongue pain whereas those treated with labial appliances experienced more lip, cheek and gum pain. Patients treated with lingual appliance reported experiencing pain earlier on than those treated with labial appliances. PMID- 22073477 TI - Computer-guided implant rehabilitation of an edentulous patient. AB - Computer-guided implant treatment is one of the popular options in the rehabilitation of dentitions in the edentulous situation. Patients should benefit not only from the advent of precise implant installation, but also the possibility of restoration of function and aesthetics immediately after the treatment. This poster presentation illustrated, from the view of the prosthodontist, the procedures and precautions involved using a clinical case as an example. PMID- 22073478 TI - Non-surgical periodontal treatment and lipid levels in diabetic patients. PMID- 22073479 TI - Nurse advocates: a patient voice. PMID- 22073480 TI - Research critique of "Registered nurses' attitudes towards the role of the healthcare assistant". PMID- 22073481 TI - Excuse me, I don't mean to interrupt you. PMID- 22073482 TI - Unique opportunity for Kentucky nurses to help children with asthma: the Healthy Hoops Kentucky program. PMID- 22073483 TI - ANA recognizes emergency nursing as specialty practice. PMID- 22073484 TI - Should residents work for free? PMID- 22073485 TI - Future interns: just fifth year medical students? PMID- 22073486 TI - The economics of medical education: a dismal science with a dismal prognosis. PMID- 22073487 TI - Evolving to meet the medical challenges of tomorrow at Saint Louis University. PMID- 22073488 TI - Money for drugs: should physicians be paid for pharmaceutical development and clinical investigations? PMID- 22073489 TI - End of life counseling. PMID- 22073490 TI - The changing climate of allergy/immunology disorders. PMID- 22073491 TI - Appropriate allergy testing and interpretation. AB - In vitro tests for specific IgE allow primary care providers to do allergy testing, which can be helpful for allergic patients. Diagnostic testing for allergies is used to determine whether symptoms are caused by IgE antibodies and exposure to an allergen. The presence of IgE in the absence of symptoms does not indicate clinical allergy. Nonselective use of large panels of allergens can lead to false positives and misinterpretation of the results, particularly in food allergy. PMID- 22073492 TI - Food allergy: practical considerations for primary care. AB - Food allergy is increasing in frequency and so is the misunderstanding of what constitutes a true food allergy. This article will review basic concepts of classic IgE reactions to food as well as discuss some that occur through other mechanisms. The importance of a detailed history is emphasized. Information is provided on optimal evaluation, interpretation of results and treatment of these potentially life-threatening reactions. Finally the role an allergist can play in co-management is discussed. PMID- 22073493 TI - Primary immunodeficiency update and newborn screening. AB - Most newborns with severe combined immunodeficiency (SCID) appear normal. Hematopoietic stem cell transplant within the first three months of life increases survival and decreases medical costs. Newborn screening measuring T cell receptor excision circles (TREC), a by product of T cell maturation, offers the opportunity for early diagnosis before infections and failure to thrive occur. The Secretary of Health and Human Services recently recommended addition of TREC to newborn screening, enabling prompt diagnosis and effective management of SCID. PMID- 22073495 TI - Approach to patients with eosinophilia. AB - Eosinophilia is commonly seen in medical practice and can underlie a variety of medical conditions. Eosinophilia, defined as peripheral blood eosinophil counts greater than 500 per microliter, may vary from mild-severe. Idiopathic hypereosinophilic syndrome has been identified as an unusual cause of moderate to severe eosinophilia. Progress in treatment of this condition has accompanied greater understanding about the basic biology of eosinophils. This review will highlight the approach to patients with eosinophilia, along with associated conditions and syndromes. PMID- 22073494 TI - Angioedema: an overview and update. AB - Angioedema is an increasing cause of hospitalizations in the United States. This syndrome presents with non-pitting, asymmetric swelling of the face, lips, tongue, larynx, genitalia, and extremities, although any part of the body can be involved. Common causes of angioedema include allergic reactions and ACE inhibitors. Hereditary angioedema is a rare form of angioedema that can be diagnosed by screening with a C4 level. In 2009, three new treatments for hereditary angioedema were approved for use in the United States, revolutionizing management of this rare disease. PMID- 22073496 TI - The impact of pharmacogenetics in the treatment of allergic disease and asthma. AB - Personalized medicine includes the application of genomic information in predicting disease and therapeutic response to ultimately individualize patient care. Pharmacogenetics is key in achieving true personalized care. However, the clinical applicability of genetic testing to "everyday medicine" is yet to be realized. This paper will discuss areas in allergic/inflammatory disease that have been impacted by pharmacogenetic research and how this application may be brought from the "bench to the bedside." PMID- 22073497 TI - Post traumatic stress disorder: part II. PMID- 22073498 TI - Prevalence of methicillin resistant Staphylococcus aureus in nasal samples from preclinical second-year medical students. AB - In other studies, around 40% of preclinical medical students were colonized with Staphylococcus aureus but none were MRSA. This study was conducted to determine the level of S. aureus and MRSA in the nares of second year medical students. Over 47% of the student samples contained S. aureus. Five percent of S. aureus isolates possessed the mecA gene. Medical students in this study had a higher percent colonization with S. aureus and MRSA than previous studies. PMID- 22073499 TI - Syndrome of inappropriate antidiuretic hormone due to multiple myeloma. AB - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been linked to many malignancies. However, literature noting multiple myeloma as a possible cause of SIADH is lacking. Although there is a plethora of literature reporting multiple myeloma induced spurious hyponatremia, our review revealed only one case report, in 1983, describing multiple myeloma induced SIADH. Here we report another case of multiple myeloma induced SIADH, where secondary causes of SIADH, including pseudohyponatremia, were ruled out. PMID- 22073500 TI - Debt crisis: opportunity for nursing action. PMID- 22073501 TI - Targeting memory improvement in assisted living: a pilot study. AB - This pilot study tested an intervention designed to improve memory for assisted living (AL) residents. Seven residents in one Midwestern AL facility participated in a six-session memory program based on qualitative research that identified typical memory challenges of residents (e.g., remembering names, schedules, and appointments). Scores on memory self-efficacy (the Memory Complaint in Age Associated Impairment) and performance (Rivermead Behavioral Memory Test) measures were compared before and after the intervention. Self-efficacy improved significantly after the program (z = 2.37, p = .018) for remembering names, phone numbers, lists of items, and facts. Increases in actual memory performance were not statistically significant. However, three out of seven participants (43%) improved in recalling first and last names. Ongoing testing on larger samples with a control group design is needed to verify effects and determine any effects on daily functioning. This study suggests that cognitive interventions targeting frail elder populations are feasible to provide to older adults in AL. PMID- 22073502 TI - Function-focused care and changes in physical function in Chinese American and non-Chinese American hospitalized older adults. AB - Function-focused care (FFC) is a rehabilitative philosophy of care with which nurses help patients engage in activities of daily living and physical activity with the goal of preventing avoidable functional decline. This prospective, observational study described the degree of FFC provided by nursing staff to Chinese American (n = 32) and non-Chinese American (n = 43) older adults in medical-surgical units of an urban hospital. In both groups, only a few ADLs were a focus of FFC. Loss of physical function occurred, and physical function did not return to baseline by discharge in both groups; however, FFC was associated with less decline. Results suggest that hospitalized elders, both Chinese American and non-Chinese American, can benefit from nurse-led FFC. FFC may help minimize functional decline and decrease the use of postacute care rehabilitation. The gerontological rehabilitation nurse can play an essential role, guiding a function-focused approach throughout the hospital stay, including with the transitional care plan. PMID- 22073503 TI - The Mauk Model for Poststroke Recovery: assessing the phases. AB - Despite the estimated 795,000 strokes occurring in America annually (American Heart Association, 2009), few practical models guide nurses when they provide quality care to stroke survivors. The Mauk Model for Poststroke Recovery is a theoretical framework concerning six phases of poststroke recovery. The purpose of this article is to discuss a pilot study detailing the ways in which nursing students used the Mauk model to identify these phases of stroke recovery via patient case examples. A sample of 30 volunteer nursing students read five case studies and determined the phase of stroke recovery. Descriptive statistics about sample characteristics and frequencies were calculated using SPSS 14 for Windows. Nearly 57% (n = 17) of the students rated all of the case studies to the correct phase. Ways in which the model might be clarified and used as a valuable tool when assessing the phase of stroke recovery are described. PMID- 22073504 TI - Biomechanics and injury risk assessment of falls onto protective floor mats. AB - This study investigated the biomechanics of simulated sideways falls from various bed heights onto two types of protective floor mats. This article presents biomechanical injury criteria for evaluating the probability of sustaining injuries to the head, thorax, and pelvis. A side-impact dummy was raised to drop heights of 45.7 cm, 61.0 cm, and 76.2 cm and released. Two types of protective floor mats were evaluated and compared with impacts experienced on an unpadded, rigid floor. Results of the study demonstrated a high risk (> 50%) for serious head injury for falls onto an unpadded, rigid floor at 61.0-cm and 76.2-cm drop heights. Falls onto floor mats demonstrated significant reductions in injury risk to the head and pelvis for all drop heights. Thoracic injury risk was significantly reduced for all but the highest drop height. PMID- 22073506 TI - Managing change in today's healthcare world. PMID- 22073505 TI - Teaching adults SAFE medication management. AB - One in nine visits to the emergency department is the result of a drug-related adverse event and is possibly preventable (Zed et al., 2008). The rehabilitation nurse has the opportunity to teach adults a comprehensive medication management plan that will help reduce medication errors. Most patients have minimal medication experience or instruction; this article documents the effectiveness of using a S = systematic, A = accurate, F = functional, and E = effective instructional methodology to help patients learn about their medications. The methodology helps rehabilitation nurses teach the average patient about handling, absorbing, and implementing the information. This article presents detailed instruction about the salient points of the SAFE instructional program. Several figures, a checklist, and pictures demonstrate the techniques utilized. Prevention of medication errors is emphasized throughout. PMID- 22073507 TI - Defensive medicine: what is it? PMID- 22073508 TI - Clarification on new title identification requirement. PMID- 22073509 TI - ICD-10/5010: move it or lose it! PMID- 22073510 TI - 5010: what your clearinghouse should be doing to prepare. PMID- 22073511 TI - Accountable care organizations: a real change, maybe. PMID- 22073512 TI - EHR adoption: help is here for your decision-making process. PMID- 22073513 TI - EHR update: progress on meaningful use requirements. PMID- 22073514 TI - HIT and the future of healthcare. PMID- 22073515 TI - Encryption, HIPAA and your practice. PMID- 22073516 TI - Mediastinal extragonadal seminoma presenting as severe back pain in a young male. AB - Back pain is a common complaint in the outpatient setting. The etiology is most often benign but it can be a serious, even life-threatening problem. This report describes a 33-year-old Caucasian male who presented with severe upper back pain for three weeks that did not respond to symptomatic outpatient treatment. Imaging studies revealed a mediastinal mass and lymphadenopathy with superior vena cava and tracheal compression. Pathology showed a poorly-differentiated malignant neoplasm consistent with seminoma. No evidence of primary testicular tumor was found. His atypical presentation of back pain was thus consistent with an extragonadal seminoma in the mediastinum. PMID- 22073517 TI - Multiple myeloma with hypercalcemia and chloride resistant metabolic alkalosis. AB - This report describes a novel presentation of chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM). A 51 year-old male with newly diagnosed MM presented with widespread skeletal involvement, calcium (Ca(+2)) of 18 mg/dL, phosphorous (PO4) of 6 mg/dL, serum bicarbonate (HCO3) of 37 mEq/L, and serum creatinine (Cr) of 2.6 mg/dL Other causes of metabolic alkalosis such as vomiting, diuretics, alkali ingestion, mineralocorticoid excess and hypokalemia were excluded. Hypercalcemia and metabolic alkalosis were only partially corrected after rehydration, calcitonin and steroids. Subsequent treatment with zoledronic acid resulted in resolution of hypercalcemia and correction of metabolic alkalosis.The chloride resistant component of metabolic alkalosis was most likely related to extensive release of Ca(+2), carbonate and phosphate from bone by activated osteoclasts with inhibited osteoblastic activity. The additional reduction in glomerular filtration rate due to MM, contributed to a triad mimicking Calcium-Alkali syndrome. PMID- 22073518 TI - Back to basics, medication safety at the bedside: a nursing administrator's perspective. PMID- 22073519 TI - Making all your professional dreams come true: the Center for Professional Excellence at Lehigh Valley Health Network. PMID- 22073520 TI - More than a thank you: the DAISY Award for Extraordinary Nurses. AB - The DAISY Award for Extraordinary Nurses was established to thank the nursing profession. This article describes the DAISY Award and its positive effects on retention at an urban hospital in Philadelphia. PMID- 22073521 TI - Your environment, your health. PMID- 22073522 TI - Pathway to excellence: creating a practice environment that makes a difference. PMID- 22073523 TI - We rise....in the face of adversity. PMID- 22073525 TI - Empowerment: healthcare professionals' and community members' contributions. AB - Healthcare disparities for minorities are well reported and related to individual, provider and system characteristics. This paper reports a meta synthesis of "empowerment with Hispanic and Latino people. This meta-synthesis utilized Noblit and Hare's meta-ethnographic method (1988) examining seven qualitative studies to discover strategies of empowerment by healthcare professionals for Hispanic/Latino people. Three themes were disclosed: strategies for empowerment, sharing power, and growth of the Hispanic/Latino culture in the United States. These themes expand existing conceptualizations of ways in which health care professionals and community members can work in a participatory research approach to improve healthcare outcomes as well as empowering the community. PMID- 22073524 TI - Picuriste/injectionist use among Haitian immigrants in Miami-Dade County, Florida: implications for HIV-related theory. AB - OBJECTIVES: We explore the risks reported to picuriste (injectionist) use in a non-probability sample of Haitian immigrant residents of Miami-Dade, Florida, using a mixed method approach. Picuristes typically have no formal medical training, and may use non-sterile needles. METHODS: Face to face semi-structured interviews were conducted of picuristes (n = 10) and picuriste users (n = 25). We sought to corroborate the qualitative findings by fielding a survey based on the interviews in a community-based sample of 205 Haitian immigrants. RESULTS: The findings from the interviews indicate picuriste injections do not adhere 100% to established standards for safe injections, and may pose health risks that are similar to those that exist for injection drug users. Yet, of the survey respondents (n = 205), 17.6% reported obtaining picuriste injections. CONCLUSION: Our findings shed light on a normally hidden cultural health behavior, enhancing our understanding of picuriste practice and use among Haitian immigrant residents of Miami-Dade County, Florida. We suggest that medical care must be delivered in a culturally competent, culturally sensitive manner, with open dialogue between physician and patient regarding health beliefs and practices. PMID- 22073526 TI - Academic partnerships and key leaders emerging from communities in the lower Mississippi Delta (LMD): a community-based participatory research model. AB - Collaboratively, the nutritional health problems of the Lower Mississippi Delta (LMD) region were examined and opportunities identified for conducting research interventions. To combat the nutritional health problems in the LMD, community residents yielded to a more comprehensive and participatory approach known as community-based participatory research (CBPR). Community residents partnered with academic researchers and other organizational entities to improve the overall quality of diet and health in their respective communities using CBPR. The collaborative work in the LMD focused on interventions conducted in each of three specific communities across three states: Marvell, Arkansas (Marvell NIRI), and its surrounding public school district; Franklin Parish in Louisiana (Franklin NIRI); and the city of Hollandale, Mississippi (Hollandale NIRI). This paper examined some of the research interventions conducted in Franklin, Hollandale, and Marvell NIRI respectively, how leadership emerged from each of these communities, and lessons learned as a result of the CBPR model. PMID- 22073527 TI - Assessing knowledge of Sudden Infant Death Syndrome among African American women in two Mississippi communities. AB - PURPOSE: Sudden Infant Death Syndrome (SIDS) is the third leading cause of Mississippi infant mortality with nonwhite infants dying of SIDS at two to three times the rate of white infants. The purpose of this study was to assess the level of SIDS related knowledge among African American women in two geographical areas of Mississippi and gain insight on improving methods for SIDS education and outreach. DESIGN: An African American faculty was contracted to conduct six focus groups among African American women (n = 57) in two geographical areas of the state. FINDINGS: Themes were common among participants from both the metropolitan and rural Delta communities. Participants in both geographical areas were familiar with [or at least had previously heard] the term SIDS. Unfortunately, there was inconsistency among participants as to the source of information. Given the inconsistencies, it is not surprising that overall knowledge related to SIDS was incomplete and in some cases inaccurate. DISCUSSION/CONCLUSION: Some information regarding SIDS is available in the various communities. Unfortunately, the information is not fully understood and is not consistently distributed resulting in a lack of knowledge among these women and thus, a continued risk for high rates of SIDS events in Mississippi. PMID- 22073528 TI - It ain't what you say, it's how you say it: linguistic and cultural diversity in the classroom. AB - The disparity between the cultural and linguistic diversity of the teaching population and the student population continues to grow as teacher education programs enroll and graduate primarily white teacher candidates (83.7%). At the same time, the diversity of the K-12 student body has increased with 65% of public school students being from culturally and linguistically diverse backgrounds (National Center for Education Statistics, 2007). This chasm between the diversity of the teaching force and student population is of concern as many teachers report that they do not have the cultural knowledge and experience of working or living in diverse environments, yet will be faced with teaching a very diverse student population. Hence, the need for teacher candidates and current teachers to be explicitly taught the skills needed to successfully teach diverse student populations is urgent. In this article, we explore the following phenomena: how linguistic and cultural diversity is regarded in teacher education programs, as well as teacher candidates' and current K-12 teachers' dispositions towards students who do not share their cultural backgrounds or language (including those who vary in their dialects). Finally, we will present strategies that teacher educators can use to embrace and empower culturally and linguistically diverse (CLD) teacher candidates, as well as prepare teacher candidates to teach diverse student populations. PMID- 22073529 TI - Spies, vaccines and violence: fake health campaigns and the neutrality of health. PMID- 22073530 TI - Keeping a place for health; the role of health professionals. PMID- 22073531 TI - The future of Trident. PMID- 22073532 TI - Evaluation of medical supplies essential for the care of survivors of sex- and gender-based violence in post-conflict Eastern Democratic Republic of Congo. AB - The fundamental concepts set forth in the formal Post-Conflict Needs Assessment (PCNA) initiative created by the United Nations Development Group have the potential to be adapted to assist local groups in documenting the needs of and the provision of health care to survivors of sex- and gender-based violence (SGBV) in Eastern Democratic Republic of Congo (DRC). In partnership with Congolese health care providers, we took the first step in advocating for a locally-adapted and focused needs assessment through the development and administration of surveys to providers in the South Kivu Province, DRC. The content of the surveys was largely based on lists of medical supplies deemed essential for reproductive health and for the care of survivors by the Reproductive Health Response in Crises Consortium. The providers in both urban and rural settings considered many of the supplies identified on the surveys necessary for the care of survivors (84%; p < 0.05) but considered few accessible (26%; p < 0.05) in their particular clinical settings. Providers also felt that the existing list of supplies was inadequate to meet the needs of survivors, and also that providers needed ongoing training to improve supply procurement and management, more knowledge of the needs of male survivors of SGBV, and more educational opportunities to improve the quality of care to survivors. Given the deficiencies expressed by providers in the surveys, this study demonstrated a critical need for a locally-adapted and focused needs assessment to improve health services to survivors. PMID- 22073533 TI - An agent-vector-host-environment model for controlling small arms and light weapons. AB - Armed violence is a significant public health problem. It results in fatal and non-fatal injuries and disrupts social and economic processes that are essential to the health of individuals and communities. We argue that an agent-vector-host environment model can be helpful in understanding and describing the availability and misuse of small arms and light weapons. Moreover, such a model can assist in identifying potential control points and in developing mitigation strategies. These concepts have been developed from analogous vector control programs and are applied to controlling arms to reduce their misuse. So-called 'denormalization' and 'de-legitimization' campaigns that focus on the vector - including the industry producing these commodities - can be based on the experience of public health in controlling tobacco use and exposure. This model can assist health professionals, civil society and governments in developing comprehensive strategies to limit the production, distribution and misuse of small arms and light weapons. PMID- 22073534 TI - [Designer drugs in Finland]. AB - Designer drugs are synthetic psychotropic drugs which are marketed as "legal drugs". Their emergence, rapid spreading and unpredictable effects have challenged the health and substance abuse care. The slow process of classification of an abusable drug has provided too many possibilities for spreading the designer drugs. Once a certain substance receives an illegal drugs classification, dealers and users usually move to another, slightly different molecule that is still legal. In Finland, the Narcotics Act has been amended to the effect that the addition of a new substance to the illegal drug list does not require an amendment to the law. PMID- 22073535 TI - [First-line bevacizumab in ovarian cancer]. AB - Based on encouraging Phase II data, two randomized phase III trials (GOG218 and ICON7) aimed at showing a progression-free survival (PFS) benefit of bevacizumab combined with first-line paclitaxel and carboplatin, followed by maintenance bevacizumab, in ovarian cancer. The median PFS increased to four and two months, respectively, as compared to chemotherapy alone. However, these two trials left important questions like proper patient selection, optimal dose level and length of maintenance phase, unanswered. Neither do we know if the quite modest progression-free survival benefit will translate into an overall survival benefit. Consequently, first-line bevacizumab in ovarian cancer cannot at present be recommended. PMID- 22073536 TI - [Mechanical support for the heart and circulation in adults]. AB - In severe, acute or chronic heart failure, the heart and the circulation can be mechanically supported, if the patient's life is in danger despite maximal drug therapy, and other cardiologic or heart surgery treatment options or a suitable heart transplant are not available. Long-term prognosis of those treated with mechanical support has improved in the 2000's. This is based on technically advanced equipment, improved treatment practices, properly targeted patient selection and more accurate timing of therapy. PMID- 22073537 TI - [Application of extracorporeal membrane oxygenation therapy (ECMO) in the treatment of severe adult respiratory distress syndrome]. AB - Extracorporeal oxygenator is used in severe respiratory and/or circulatory failure that is intractable to other therapies. In ECMO therapy, poorly oxygenated blood is pumped through an extracorporeal oxygenator and directed back to the patient's circulation. The therapy can be utilized to maintain the homeostasis of the organ system during circulatory or respiratory failure resulting from a disease. Due to risk of complications, ECMO should be used with caution on carefully selected patients. For a severely ill patient ECMO can be life-saving when started early. PMID- 22073538 TI - [Fruit fly--genetically excellent model animal for research]. AB - Drosophila melanogaster, i.e., the fruit fly is a familiar nuisance in late summer. For those living in a country plagued by myriads of flying insects, it is difficult to think any other model animal as an ethically more suitable research tool. Due to its genetic manipulability, the fruit fly is an excellent research model, but mainly due to lack of experience, has been utilized only to a small extent in medical research in Finland. For instance, the readily available transgenic RNAi strains have made functional, genome-wide screening possible in a complete organism or in a designated tissue. PMID- 22073539 TI - [Information retrieval and reading routines in medical students]. AB - For a physician working as an expert continuous following of scientific literature is required. We elucidated the competence of 5th and 6th year students for the development of expertise. The mean time spent on reading medical literature was seven hours a week. The most important source of information for the students were websites with short quidelines and introductions written in students' own language. International original articles or English textbooks were not so much appreciated and seldom read. The present curricula in our medical schools do not encourage the student to search and acquire knowledge wider than their patients themselves do. PMID- 22073540 TI - [Idiopathic thrombocytopenic purpura (ITP) in children]. AB - Thrombocytopenia associated with ITP in children usually returns to normal within a couple of months. Drug therapies are required to treat hemorrhages in approximately one fifth of the patients. Intravenously infused immunoglobulin is effective more rapidly than corticosteroid therapy, but the treatment response is mostly temporary. Thrombocytopenia is alleviated by splenectomy in approx. 70% of chronic ITP patients. In the absence of primary disease causing thrombocytopenia, splenectomy has to be contemplated, if thrombocytopenia impairs the quality of life for more than one year. New drug therapies such as rituximab and growth factor products increasing thrombopoiesis may decrease the number of splenectomies. PMID- 22073541 TI - [Treatment of recurrent dislocation of the temporomandibular joint with botulinum toxin: an alternative approach]. AB - Repeated injections of botulinum toxin carried out at regular intervals are an effective means to treat otherwise treatment-resistant recurrent dislocation of the temporomandibular joint. The treatment can be performed simply and safely without electromyography (EMG) or imaging control by a specialist having expertise in the anatomy of the region. In a patient described by us, a previously treatment-resistant condition has been successfully treated in this way for three years. PMID- 22073542 TI - [Phytosymbiosis of aerobic methylobacteria: New facts and views ]. PMID- 22073543 TI - [The effect of different heat influences on composition of membrane lipids and cytosol carbohydrates in mycelial fungi ]. PMID- 22073544 TI - Evidence for a sodium-dependent proline and glycine-betaine uptake in the cyanobacterium Nostoc muscorum. AB - The cyanobacterium Nostoc muscorum is able to utilized proline and glycine betaine as a nitrogen source under unstressed growth conditions. This cyanobacterium when grow in modified Chu No. 10 medium (without Na+) unable to utilized proline and glycine-betaine as a nitrogen source. Spontaneously occurring mutant clones defective in Na+ transport (Na+-R) were isolated and analyzed for proline and glycine-betaine utilization. The mutant phenotype showed normal heterocyst frequency and nitrogenase activity even in the medium containing 1 mM proline or 1 mM glycine-betaine, indicates the role of Na+ for proline/glycine-betaine uptake. The Na+-R mutant showed 100% survival at pH 11 and was simultaneously able to uptake and utilize proline/glycine-betaine at higher alkaline pH. This indicates that proline and glycine-betaine uptake systems are more efficient at higher alkaline pH. Since, the hypersaline environments are rich in Na+ contents and have alkaline pH, therefore it is suggested that the origin and evolution of specific compatible solutes may not depend only on the osmoregulatory role they play, but also on the other ecological factors operating simultaneously in the organism's niche. PMID- 22073545 TI - Adhering ability of Stenotrophomonas maltophilia is dependent on growth conditions. AB - The growth conditions are known to influence the bacterial adhesion to different kinds of surfaces. In the present study the adhering ability of Stenotrophomonas maltophilia, on growth in nutrient rich media (Tryptic Soy Broth (TSB)) and minimal media (Luria Bertani (LB)) was checked by viable cell count and spectrophotometric method. TSB grown S. maltophilia showed higher adhesion compared to bacteria grown in LB broth, to both biotic and abiotic surfaces. However, when bacteria were grown in LB broth supplemented with different concentrations of glucose, under aerobic conditions, the bacteria grown at lower glucose concentration (2 gm/l) showed maximum adhesion to abiotic surfaces (polystyrene microtiter plate) compared to biotic surfaces (mouse trachea, mouse tracheal mucus and HEp-2 cells line). Maximum adhesion to biotic surfaces was seen with cells grown at 4 gm/l of glucose concentration. On the contrary if the cell was grown under microaerophilic conditions maximum adhesion to abiotic and biotic surfaces was achieved with bacteria grown at 1 gm/l and 2 gm/l of glucose concentration respectively. A negative correlation was observed between glucose concentrations and pH of media, the latter declined faster under microaerophilic conditions as compared to aerobic condition. PMID- 22073546 TI - [Resting forms of Sinorhizobium meliloti ]. PMID- 22073547 TI - Isolation and characterization of some moderately halophilic bacteria with lipase activity. AB - Lipases are an important class of enzymes which catalyze the hydrolysis of long chain triglycerides and constitute the most prominent group ofbiocatalysts for biotechnological applications. There are a number of lipases, produced by some halophilic microorganisms. In this study, some lipase producing bacteria from Maharlu salt lake located in south of Iran were isolated. All isolates were screened for true lipase activity on plates containing olive oil. The lipase activity was measured using titrimetric methods. Among thirty three isolates, thirteen strains demonstrating orange zone around colonies under UV light, were selected for identification using the molecular methods and some morphological characteristics. The bacterium Bacillus vallismortis BCCS 007 with 3.41 +/- 0.14 U/mL lipase activity was selected as the highest lipase producing isolate. This is the first report of isolation and molecular identification of lipase producing bacteria from Maharlu lake. PMID- 22073548 TI - Evaluation of the relative cell surface charge by using microbial adhesion to hydrocarbon. AB - A simple and rapid method, Microbial adhesion to hexadecane, for estimating the cell surface charge is proposed. This method is based on the determination of cell affinity to hexadecane at low ionic strength and at high ionic strength. The difference between these two affinities can provide the relative cell surface charge. The application of this method for Staphylococcus aureus and Escherichia coli show that the profile of surface charge evolution as a function ofpH was similar to these obtained by microelectrophoresis method. PMID- 22073549 TI - Heterogeneity in the ITS of the ribosomal DNA of Pyrenophora graminea isolates differing in xylanase and amylase production. AB - Xylanase and amylase have gained increasing interest because of their various biotechnology applications. In this research, the restriction of PCR-amplified internal transcribed spacers (ITS) of ribosomal DNA (rDNA) was used to confirm the genetic variation among 22 isolates of Pyrenophora graminea differing in their xylanase and amylase production. The fingerprints generated from the six restriction digestions of the rDNA ITS region showed high levels ofintraspecific variation within the P. graminea population. Neighbour-Joining diagram, based on Nei's genetic distances, showed that isolates formed two phylogenetic groups. No apparent association could be observed between xylanase and amylase production and genetic diversity among the twenty-two isolates. PMID- 22073550 TI - [Role of the snorA gene in nogalamycin biosynthesis by strain Streptomyces nogalater Lv65 ]. PMID- 22073552 TI - [Macrokinetics of microbial growth and decline in soil ]. PMID- 22073551 TI - [Molecular polymorphism of alpha-galactosidase MEL genes of Saccharomyces yeasts ]. PMID- 22073553 TI - [Outer membrane nanovesicles of gram-negative bacteria Aeromonas hydrophila and Aeromonas salmonicida ]. PMID- 22073554 TI - [Fossilization of the cells of natronophilic endoevaporite cyanobacterium Euhalothece natronophila in a modelling system ]. PMID- 22073555 TI - [Novel ultramicrobacteria, strains NF4 and NF5, of the genus Chryseobacterium: Facultative epibionts of Bacillus subtilis ]. PMID- 22073556 TI - [Phylogenetic composition of bacterial communities in small boreal lakes and ombrotrophic bogs of the upper Volga basin ]. PMID- 22073557 TI - Studies on mineral phosphate solubilization by cyanobacteria Westiellopsis and Anabaena. AB - Two diazotrophic cyanobacteria, Westiellopsis prolifica and Anabaena variabilis were evaluated for elucidating the possible mechanism of mineral phosphate solubilization. Phosphate starved cyanobacteria evaluated for the presence of organic acids, extracellular compounds or enzymes that might have been produced and promoted the mineral phosphate solubilization with Mussorie Rock Phosphate and Tricalcium Phosphate as substrates. Both the cultures did not reveal production of organic acids throughout the incubation period when checked for decrease in pH of the media and thin layer chromatography Thin layer chromatography of culture filtrates showed the presence of hydrocarbon like compound. Further analysis of the culture filtrates with gas liquid chromatography, a single peak near to the retention time of 7.6 was observed in all extracts of culture filtrates irrespective of phosphate source. UV-visible spectra of culture filtrates revealed the absorption maxima of 276 nm. Gas Chromatographic-Mass Spectrometric analysis of culture filtrates showed most intense peak in the electron impact (EI) ionization was at m/z 149 and molecular ion peaks at m/z 207 and 167, inferring the presence of phthalic acid. Among the mechanisms in mineral phosphate solubilization, it was evident that these cyanobacteria used phthalic acid as possible mode of P solubilization. PMID- 22073558 TI - [Compositions of microbial communities in sulfide nickel ore waste piles ]. PMID- 22073559 TI - [Hydrophobic and donor-acceptor properties of the surface of Warnerin-sensitive or -resistant staphylococcus cells ]. PMID- 22073560 TI - [Microbial communities of water column of Lake Radok, East Antarctica, dominated by abundant actinobacterium "Candidatus Planktophila limnetica"]. PMID- 22073561 TI - [Pathophysiology of peripheral airway obstruction underlying COPD]. PMID- 22073562 TI - [Concept of COPD, from past to the present]. AB - The clinical concept of COPD initially started in conjunction with American Emphysema and British Bronchitis in CIBA Guest Symposium in 1958. JC Hogg, et al. recognized the peripheral airways as the major site of airflow obstruction in COPD in 1968. Thirty-six years later in 2004, JC Hogg, et al. described the pathological nature of small-airway obstruction in COPD. The GOLD project provided state-of-the-art information about COPD in 2001, in which it is stated that the chronic airflow limitation characteristic of COPD is caused by a mixture of small airway disease and parenchymal destruction. Cigarette smoke may accelerate the aging of lung or worsen aging-related events in lung by defective resolution of inflammation. Accelerated decline in lung function is recognized to occur in asthma, especially in those with asthma who smoke. With increasing age, there was a greater increase in the proportion of patients with overlapping COPD and asthma. PMID- 22073563 TI - [Epidemiology of COPD in Japan]. AB - The prevalence of COPD in Japan is revealed to be 8.6 % which is almost the same as foreign countries. However, there are many undiagnosed COPD patients. More than half of undiagnosed COPD patients go regularly to medical institution with other diseases. Among the patients who are 40 or more and go clinics with non respiratory diseases, the prevalence of COPD is 8.6 to 10.3 %. If they have smoking history or some respiratory symptoms, the prevalence of COPD is 22 %. In Japanese reports, atherosclerosis is detected in 73.8 % of COPD patients, and the prevalence of COPD is high in heart failure, ischemic heart failure and liver diseases. The effort to decrease the mortality of COPD in Japan is necessary. PMID- 22073564 TI - [Guidelines for the diagnosis and management of chronic obstructive pulmonary disease: 3rd edition]. AB - The third edition of COPD guidelines of the Japanese Respiratory Society can provide clinicians with practically applicable information covering all the main points such as definition, stage classification and severity, treatment and management, COPD with asthma, and clinical care system. The guidelines are clear and useful in the diagnosis and management for COPD as complex disease or syndrome. PMID- 22073565 TI - [Cigarette smoking is the most important causal factor for developing chronic obstructive pulmonary disease (COPD)]. AB - Cigarette smoking is the most important causal factor for developing chronic obstructive pulmonary disease(COPD). On the other hand, a substantial proportion of COPD cases suffer from obstructive disorder by other causes than smoking, especially among younger persons, females, and residents of developing countries. There are evidences that several rare genetic syndromes(such as alpha 1 antitrypsin deficiency) and occupational exposures as causes of COPD. Environmental tobacco smoke, biomass smoke, and dietary factors are likely causes of COPD, although their contribution is much less compared to active smoking. Smoking during pregnancy may also pose a risk for the fetus, by affecting lung growth and development in uterus. The quicker the smoking cessation is achieved, the more improvements in the lung functions the COPD patients can obtain. Smoking should be avoided as soon as possible in all the COPD subjects and those who are at risk for developing COPD. PMID- 22073566 TI - [Neutrophils and macrophages related to the pathogenesis and disease development of chronic obstructive pulmonary disease by the inflammatory reaction]. AB - Chronic obstructive pulmonary disease (COPD) is a chronic airway disorder characterized by obstructive airflow limitation which is not completely reversible with treatment. Inflammatory changes in the peripheral airways, especially those with the diameter less than 2mm (so-called small airway disease) have been speculated to be initial steps of COPD. And so it must be quite clear that neutrophils and macrophages play an essential role in the pathogenesis of these lesions. Studies with bronchoalveolar lavage demonstrated an increase in neutrophil numbers and the neutrophil chemoattractant interleukin-8. Recent studies demonstrated that neutrophils and macrophages are increased and contain a variety of proteases, which are involved in cell infiltration and activation. Studies with gene-engineered animals and anti-cytokine treatment will facilitate better understanding the role of neutrophils and macrophages, and eventual novel therapy. PMID- 22073567 TI - [Cytokines and proteases involved in pathogenesis of COPD]. AB - COPD is characterized by persistence of chronic inflammation in small airways and alveoli. Macrophages, neutrophils, and a specialized subset of T lymphocytes orchestrate the mild inflammation. This article focuses on humoral factors such as cytokines and chemokines that recruit these inflammatory and immune cells to the lungs, and proteases/antiproteases that ultimately cause structural derangement in the terminal respiratory zones. In addition to the classical protease and antiprotease imbalance hypothesis, alveolar homeostasis abnormality that comes from imbalance of lung constitutional cell apoptosis and regeneration may play a role in emphysema development. Also, autoimmunity to elastin degradation products may take part in the disease. PMID- 22073568 TI - [Roles of apoptosis, cell senescence, and DNA damage in the pathogenetic mechanism of COPD]. AB - Pulmonary emphysema is a dynamic phenomenon involving not only the gradual destruction of extracellular matrix by excess of proteases, but also apoptosis, cell proliferation, and senescence. Cellular proliferation compensates for enhanced alveolar cell apoptosis whereas cell senescence caused by cigarette smoking and increased cell turnover halts cell proliferation, tipping the balance toward apoptosis. As a result, alveolar cells gradually disappear and emphysematous lesions advance. At the same time, cellular senescence causes chronic inflammation through enhanced production of proinflammatory cytokines. Recent findings suggest that DNA damage (double strand breaks) underlies the molecular mechanisms of apoptosis, cell senescence, and chronic inflammation in emphysematous lungs. PMID- 22073569 TI - [Genetics of chronic obstructive pulmonary disease]. AB - Chronic obstructive pulmonary disease (COPD) is a complex disease that results from the interaction of multiple genetic and environmental factors. Different approaches have been used to identify the genetic factors: genome-wide linkage study, gene expression profiling, candidate gene association study, and genome wide association study. Although many genes responsible for susceptibility to COPD have been reported, most of them have not been replicated in other study populations. Difficulty in replication is attributed to the genetic and phenotypic heterogeneity of the disease as well as the small influence of each gene on the development of the disease. A more precise definition is required for the characterization of different COPD phenotypes such as emphysema and small airway disease. A combination of several approaches using the improved phenotypes will lead to detection of novel susceptibility genes and new therapeutic targets. PMID- 22073570 TI - [Classification and the staging of chronic obstructive pulmonary disease and assessment of determinant factors of prognosis]. AB - Classification of the stage of COPD is based on flow limitation such as post bronchodilator FEV1. GOLD guideline and JRS guideline, and other guidelines are almost similar standards. But prognosis is not determined only FEV1. COPD is recognized not only lung disease but also systemic disease. This is a reason why the multidimensional estimation is needed. Prognostic factors are proposed for many studies, for example exercise capacity (6MWD, VO2max), BMI, dyspnea score, BODE index, and so on. BODE index is a multidimensional index, consist of 4 categories such as BMI, airflow obstruction, dyspnea, and exercise capacity. High BODE index means poor prognosis. Exacerbation frequency and fibronectin/CRP ratio proposed as prognostic factors too. PMID- 22073571 TI - [Clinical findings of chronic obstructive pulmonary disease]. AB - Patients with chronic obstructive pulmonary disease(COPD) can show various unique clinical findings. Whenever we examine smokers or ex-smokers, especially for those with chronic productive cough or dyspnea on effort, we have to pay attention to whether they would have clinical manifestations associated with COPD. Making physical diagnosis is quick and requires few costs. Rapid physical diagnosis of COPD in primary care practice can also lead to earlier actions of preventive measures and counseling for patients regarding smoking cessation. Furthermore, rapid physical diagnosis of COPD in an emergency department could be crucial for timely implementation of potentially lifesaving management specific for COPD patients. In this review, we will present an extensive list of clinical findings of COPD patients. PMID- 22073572 TI - [Comprehensive management for the comorbidities and pulmonary complications in COPD]. AB - Chronic obstructive pulmonary disease (COPD) has been recently recognized not only as inflammatory airway disorders, but also as a chronic systemic inflammatory syndrome. The systemic inflammation causes a variety of abnormalities in the patients. In the end, systemic comorbidities including cardiovascular diseases, endocrine diseases, gastrointestinal diseases and psychological disorders are highly prevalent in patients with COPD. These disorders and those related pulmonary complications have a great impact on quality of life (QOL) and mortality in the patients. For the improving the QOL and the mortality, we have to diagnose these comorbidities early and to treat the complications properly. This review discusses pathogenic mechanisms of the comorbidities and implications for the comprehensive management in patients with COPD. PMID- 22073573 TI - [Differential diagnosis of COPD from asthma]. AB - COPD and asthma share common features such as chronic airway inflammation and remodeling and chronic airflow obstruction, while they involve numbers of differences. The differential diagnosis of these disorders is important, because they differ in preferred treatment and prognosis. It is usually easy based on the characteristic history and physiological findings, but may sometimes be difficult especially in the elderly. The precise understanding of these disorders is therefore very essential. PMID- 22073574 TI - [Further examination of COPD using spirometry, respiratory function test, and impulse oscillometry]. AB - Spirometry is essential for diagnosis and staging of chronic obstructive pulmonary disease (COPD). Characteristic of physiological change of small airways in COPD is heterogeneous distribution of small airway narrowing, resulting in air trapping and nonhomogeneous ventilation. FEF25-75, residual volume/total lung capacity, delta N2 in phase III slope of single breath N2 washout test, closing volume, static and dynamic compliance, and carbon monoxide diffusing capacity (transfer factor) are measured for detecting small airways disease. Impulse oscillometry is also useful for assessment of small airways disease, especially indices of frequent resonance (Fres) and frequent dependent of resistance change of R5-R20; resistance at 5 Hz minus resistance at 20 Hz. Impulse oscillometry seems to have a complemental role of spirometry in managing COPD. PMID- 22073575 TI - [Diagnostic imaging--CT, dynamic CT, and others]. AB - Technical advances have raised computed tomography(CT) as a strong diagnostic tool of clinical imaging. Emphysematous changes can be quantitatively analyzed as low attenuation area which correlated with diffusion capacity, quality of life, and nutritional states, but not so much with forced expiratory volume in one second. With co-analyzing airway wall thickness, those are possibly useful to understand phenotypes. Dynamics of airway during breathing can be visualized by dynamic CT such as electron-beam CT. Dynamic airway narrowing is a representative feature in emphysematous lung. PMID- 22073576 TI - [Arterial blood gas analysis, pulse oximeter]. AB - We inspire air and get oxygen, and the storaging conditions of the oxygen in the blood are gas and solid (Hb-O2) type. To measure the gas type oxygen in the blood, we use blood gas analyzing meters, and we also can measure solid type oxygen by this method. From this method, we can get arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), pH, HCO3(-), and so on. By the way, pulse oximeter is an equipment to measure percutaneous arterial oxygen saturation (SpO2). Although the PaO2 and SpO2 are essential parameters to know the clinical conditions of COPD patients, we should be aware of the primary differences between them, and use these parameters effectively. PMID- 22073577 TI - [Airway biomarkers in chronic obstructive pulmonary disease]. AB - Inflammation plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Monitoring of inflammation of the airways has, therefore, become a growing are of research and there is particular interest in noninvasive approaches which allow frequent monitoring. Induced sputum has provided important insights into airway inflammation in COPD. However, induced sputum is relatively invasive. This has focused attention on other noninvasive methods. Exhaled breath condensate has the potential to measure semi-volatile lipid mediators. However, a major problem limiting the usefulness of this technique is variable dilution with water vapor and low concentrations of mediators. Many volatile organic compounds have been detected in the breath and the pattern of molecules can now be characterized with various electronic noses. PMID- 22073578 TI - [Exercise test and respiratory muscle function test]. AB - Dyspnea on exertion is a chief complaint of patients with COPD, and it has a major effect on the quality of their lives. Dyspnea is, by definition, subjective, but objective approaches are needed for a comprehensive understanding of these patients' conditions. Thus, measuring changes in cardiopulmonary variables during exercise can be very helpful when evaluating patients with COPD. The main purpose of exercise testing is to evaluate exercise tolerance and to identify the factors limiting exercise. Although incremental exercise testing is ideal for these purposes, simple walking tests such as 6-minute walking test, are also useful. PMID- 22073580 TI - [Pharmacologic treatments of COPD depending on disease severity]. AB - Depending on decreases in lung function and severity of symptoms, treatment with bronchodilators, including beta2-agonists and anticholinergics, is performed in pharmacologic treatments of COPD. Methylxanthines are also frequently used in Japan. As-needed use of short-acting bronchodilators is recommended for patients with mild COPD for relief of symptoms. Regular treatment with long-acting bronchodilators is more effective than treatment with short-acting bronchodilators. Inhaled beta2-agonists and anticholinergics in combination are more effective than either agent alone. Combining bronchodilators with different mechanisms of action may increase the effects of bronchodilation, may improve symptoms and quality of life, and reduce the frequency of exacerbations. Inhaled corticosteroids reduce the frequency of exacerbations and improve symptoms in severe COPD. PMID- 22073579 TI - [Evidence of pharmacotherapy in COPD--key findings from recently-conducted randomized clinical studies]. AB - The primary aim of pharmachotherapy in COPD is improvement of exertional dyspnea and quality of life through its bronchodilator effects. However, there is emerging evidence that pharmacotherapy may reduce exacerbations, alleviate annual decline of pulmonary function, and even favorably affect mortality, thus changing natural history of COPD. The large-scaled randomized clinical trials, such as TORCH, UPLIFT, have revealed that combination of long acting beta2 agonist (LABA) and inhaled corticosteroids (ICS), LABA/ICS, and/or tiotropium alone may have such effects. In addition, carbocisteine, which is a mucolytic and anti-oxidant agent, has been shown to reduce exacerbations in COPD. Future directions on pharmacotherapy are personalized medicine based on phenotyping of the disease and development of new agents which may cure airway inflammation in COPD. PMID- 22073581 TI - [Novel therapeutics for COPD]. AB - Chronic obstructive pulmonary disease (COPD) is a progressing lung disorder mainly caused by cigarette smoking. The central pathogeneses are inflammation, oxidative stress, apoptosis and excessive proteases which lead to matrix degradation and loss of lung cells. The inflammation is somehow perpetuated even after quit smoking and is generally refractory to glucocorticoid therapy. It is thus hoped to develop novel anti-inflammatory agents for prevention of disease progression. As molecular mechanisms of COPD are gradually clarified, numerous numbers of molecular targeted agents have been developed for therapeutics. In this section, novel agents for COPD targeted at signal transduction molecules, cytokines, chemokines and those receptors, adhesion molecules, oxidative stress and proteases are discussed. PMID- 22073582 TI - [Smoking cessation]. AB - Smoking has been determined as a cause of chronic obstructive pulmonary disease (COPD) in most patients. Smoking cessation should be stressed above everything else for COPD patients under all conditions. A smoking habit is determined not as a preference but as a dependency on tobacco; therefore, smoking cessation is difficult solely based on one's motivation. Smoking cessation therapy is employed with cessation aids. Now, we can use nicotine-containing gum, patches, and the nicotine-receptor partial agonist varenicline. First, nicotine from tobacco is replaced with a nicotin patch, or a nicotine-free condition is induced by varenicline. Subsequently, the drugs are gradually reduced. In Japan, smoking cessation therapy is covered by public health insurance as definite requirements. PMID- 22073583 TI - [Pulmonary rehabilitation: exercise training, nutritional intervention and patient education]. AB - The optimal care of patients with COPD generally requires combining pharmacologic and non pharmacologic therapies and the latter provides as pulmonary rehabilitation. Pulmonary rehabilitation, which includes exercise training, patient education, psychosocial support, nutritional intervention, and outcome assessments. Pulmonary rehabilitation has demonstrated effectiveness over multiple outcome areas such as dyspnea, exercise capacity, and health-related quality of life compared with other interventions such as pharmacologic therapy. However, it is not enough access for pulmonary rehabilitation, so effort should be made for easy access of this effective medical care. PMID- 22073584 TI - [Long term oxygen therapy and mechanical ventilation for patients with COPD]. AB - Non-drug treatments such as long term oxygen therapy (LTOT) and non-invasive positive pressure ventilation (NPPV) are thought important for patients with chronic obstructive pulmonary disease (COPD). It is reported that LTOT can improve the prognosis of patients with COPD, particularly who have severe respiratory failure. NPPV attracted attention to avoid endotracheal intubation and high efficacy in patients with acute exacerbation of COPD. In chronic phase of COPD, NPPV may improve the quality of life in patients with hypercapnia, selected carefully. PMID- 22073585 TI - [Surgical and bronchoscopic treatment for COPD]. AB - Lung volume reduction surgery (LVRS) has been proved as the safe, effective, and durable treatment which improves life-span, exercise tolerance, QOL, and dyspnea in patients with severe COPD selected appropriately by distribution of emphysema (upper lobe vs non-upper lobe) and exercise capacity(low vs high) through the National Emphysema Treatment Trial (NETT) as well as previous or concurrent reports of clinical studies. However, this procedure has not always been offered to those patients who might benefit from it these years because of significant morbidity and mortality during perioperative period and in part because of misleading in early results of the trial. On the other hand, nonsurgical procedures, such as endobronchial valve to intend collapse of the emphysematous lung, extra-anatomical airway bypass to eliminate excessive residual lung volume, and remodeling of emphysematous lung with biological adhesives or vapor ablation have been proposed as alternative treatments for emphysema recently. However, efficacy and duration of these bronchoscopic lung volume reduction procedures are less than those of LVRS, and issues to be clarified remain. LVRS should be re considered as a promising and practical tool for patients with emphysema confronting severe dyspnea during daily activities. PMID- 22073586 TI - [Treatment for exacerbation--drug and non-drug therapy, criteria of hospitalization and ICU admission]. AB - It is necessary to evaluate the degree of severity and make a diagnosis of exacerbation factor for acute exacerbation of COPD patients. The highest frequency exacerbation factors are respiratory infection and aerial pollution, so clinical examinations and treatments should be done in consideration of these exacerbation factors. In case of respiratory failure, it is preferable to treat a patient in the hospital. Furthermore, it is important to evaluate the type of respiratory failure, in other words, with or without of hypercapnia. When patients have respiratory failure with hypercapnia, ventilatory assisit therapy is necessary in addition to oxygen therapy. Moreover, it is very important to prevent exacerbation, because patients of COPD exacerbation have poor prognosis and QOL. PMID- 22073587 TI - [Regenerative approach for COPD]. AB - No treatment to cure of chronic obstructive pulmonary disease (COPD) is available. Regenerative medicine is one of promising areas for this intractable disease. Several reagents and growth factors are known to promote lung regeneration in small animal models. However, regenerative medicines for human lungs are not achieved yet. Recent advances in stem cell biology and tissue engineering have expanded our understanding of lung endogenous stem cells, and this new knowledge provides us with new ideas for future regenerative therapy for lung diseases. Although lungs are the most challenging organ for regenerative medicine, our cumulative knowledge of lung regeneration and of endogenous progenitor cells makes clear the possibilities for regenerative approach to COPD. PMID- 22073588 TI - [Current status and future of lung transplantation]. AB - Lung transplantation has been a widely accepted treatment modality for patients with end-stage chronic obstructive lung disease (COPD). COPD is the most frequent indication for lung transplantation according to the report from International Society for Lung and Heart Transplantation. However, it is a minor population in Japan. A total of 204 lung transplants have been performed in Japan to date. Among them, 10 patients were suffering from severe COPD. Nine of them received cadaveric lung transplantation and one received living-donor lobar lung transplantation. All are currently alive during follow-up period of 3-87 months. PMID- 22073589 TI - [Concept of teamwork and inter- and intra-connection for better management of COPD patients]. AB - The elderly population makes up a majority of the patients with chronic obstructive pulmonary disease (COPD), and more than 90 % of these patients have mild or moderate severity of COPD. Furthermore, in general, most severe cases receiving occasional long-term oxygen therapy may show a gradual decline in the activity of daily living and/or a cognitive impairment during the clinical course. These conditions together with the fact that in most cases the medical facility is far from patient's home prevent them from regularly visiting chest physicians at a large community hospital; therefore, they are possibly managed by non-specialists at private clinics. Recently, there have been significant advances in COPD management, and evidences of its appropriate pharmaceutical treatment are now available. Thus, there is a need for translational research with the recent advances in COPD management. This manuscript describes the concept of teamwork and inter- and intra-connection for better management of COPD patients. PMID- 22073590 TI - [Genetic analysis for nicotine dependence]. AB - Smoking cessation is extremely important to prevent the development of the serious diseases, such as COPD and cancers. Absorbed nicotine through smoking into the body is mainly metabolized by cytochrome P450 (CYP) 2A6. On the other, the nicotine acts in the brain through neuronal nicotinic acetylcholine receptors (nAChRs), which regulate the addictive properties of nicotine. Many associated studies have implicated genetic backgrounds influence smoking behavior and nicotine dependence. In these concepts, we here discuss the genes related to nicotine dependence from the pharmacokinetic and pharmacodynamic aspects of nicotine. Referring to the genome association studies, better understanding the molecular mechanisms of nicotine dependence would help to design targeted, more effective therapies for the tobacco-related diseases and smoking cessation program. PMID- 22073591 TI - [Mechanisms of cellular senescence by tumor suppressor p53]. AB - Cellular senescence is a complexity of ageing and cancer biology. As malignant tumors can culminate individuals in life-termination, evolution has provided multicellular organisms with an acquisition of distinctive safety device, cellular senescence, to circumvent the development. Diploid cells, indeed, sense accumulation of hostile stresses such as genomic integrity, metabolic dysfunction and oncogene-induced mitotic signals, leading to activation of cell cycle arrest and/or programmed cell death. A tumor suppressor, p53, has been reported to function as a governing center to defend against these malignant transformations. Here we review how p53 cooperate with adverse stresses to drive cellular senescence, providing a framework for intricate molecular cross-talks. PMID- 22073592 TI - [Current state and measures of NSAIDs induced ulcer]. AB - In recent years, the incidence of Helicobacter pylori (H. pylori) infection has been decreasing and the incidence of peptic ulcer and bleeding ulcer induced by NSAIDs, especially low-dose aspirin (LDA), have been increasing. PPI and PG are useful for treatment and prevention of ulcers in patients receiving continuous administration of NSAIDs and/or LDA. H. pylori eradication is effective if performed before the start of NSAIDs administration, but a beneficial effect of H. pylori eradication performed during NSAIDs treatment cannot be expected. The incidence of ulcers is lower when administering COX-2-selective inhibitor than when administering non-selective NSAIDs, but attention must be given to cardiovascular events as side effects when administering COX-2-selective inhibitor. PMID- 22073593 TI - [Clinical investigation of multidrug-resistant tuberculosis --investigation of inpatients in the Kyushu region between 2004 and 2009]. AB - OBJECTIVE: To conduct a clinical investigation of patients with multidrug resistant (MDR) tuberculosis who received either drug therapy alone or drug therapy in combination with surgery. SUBJECTS AND METHODS: A total of 56 patients with MDR tuberculosis who were admitted to hospitals of the National Hospital Organization in the Kyushu region between January 2004 and September 2009 and received drug therapy either alone or in combination with surgery were investigated. RESULTS: As surgery could not be performed in patients with advanced age or with bilateral extensive lesions, only 12 patients (21%) were able to undergo surgery. Initial drug resistance was seen in 10 patients (23%) in the drug therapy group and four patients (33%) in the combination therapy group. Underlying diseases included diabetes in 15 patients (34%) in the drug therapy group and in 6 patients (50%) in the combination therapy group. Negative conversion of the sputum culture result was observed in 43% in the drug therapy group and in 75% in the combination therapy group. The death within three years was seen in 20 patients (45%) in the drug therapy group and 1 patient (8%) in the combination therapy group. In the drug therapy group there were more cases with resistance to 5 drugs, resistance to levofloxacin (LVFX), and/or kanamycin (KM) in those who died of tuberculosis than in non-tuberculous death cases. CONCLUSION: Resistance to 5 drugs, resistance to LVFX, and resistance to KM were contributing factors of tuberculous death. Patient's operability was one of the factors associated with a good prognosis. PMID- 22073594 TI - [A case of pleural tuberculoma with intra-pulmonary invasion during anti tuberculosis therapy]. AB - A 27-year-old woman who had been treated for pulmonary tuberculosis with anti tuberculosis drugs for three months was admitted to our hospital because of pain in the chest and back. Chest CT showed improvement in the pulmonary tuberculosis lesions in the right middle lobe and S8, but there was a large pleural mass in the right lower lung field. Histopathological findings of the percutaneous biopsy showed epithelioid cell granulomas that were negative for acid-fast bacilli. We diagnosed the mass as pleural tuberculoma with intrapulmonary invasion. The pleural tuberculoma improved without any additional therapy. PMID- 22073596 TI - [Problems in the treatment for proliferative vitreoretinopathy]. PMID- 22073595 TI - [Pulmonary tuberculosis with atypical radiological findings in a patient with chronic obstructive pulmonary disease]. AB - A 77-year-old-man who had been treated for chronic obstructive pulmonary disease (COPD) was referred to our hospital for further examination of a chest X-ray abnormality. The chest X-ray showed consolidation in the right upper and middle lung field. Chest computed tomography showed an airspace consolidation extending subpleurally and nonsegmentally without nodular lesions. The tentative diagnosis was cryptogenic organizing pneumonia. However, bronchoalveolar lavage fluid was positive for acid-fast bacilli on smear and also positive for tuberculosis PCR, leading to a diagnosis of tuberculous pneumonia. Tuberculous pneumonia in COPD patients can be non-segmental and mimic organizing pneumonia. PMID- 22073597 TI - [Determination of causative agents in ocular infection of external adnexa and anterior segments--multicenter study of causative agents and drug sensitivity of ocular infection by the Japanese Association for Ocular Infection part I]. AB - PURPOSE: To determine the causative agents of ocular infection of external adnexa and anterior segments due to selected criteria. SUBJECTS AND METHODS: Between September 22, 2007 and August 25, 2008, 890 bacterial strains were collected from 476 patients in 18 facilities nationwide participating in the Drug Sensitivity for Ocular Infection Study Group. Usual aerobic and anaerobic cultures, enrichment cultures, smears, and measurements of bacterial quantity were performed and the determination of causative agents was made from the results of smears and culture, the presence of polymorphonuclear cells and bacterial quantity. The selection was divided into two categories, causative agents and presumed causative agents. Staphylococcus aureus, Moraxella bacilli, Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Neisseria gonorrhoeae were distinctively considered as specified bacteria. RESULTS: Among 890 strains, 18.8% were determined to be causative agents, and 15.1% were determined to be presumed causative agents. Among the bacteria detected in normal flora, 2.0% of Staphylococcus epidermidis, 2.6% of Propionibacterium acnes, and 38.3% of Corynebacterium spp. were determined to be causative agents. CONCLUSION: To determine the causative agents, the results of smears and bacterial quantity should be considered together with culture results. Bacteria constituting normal flora have the potential of becoming causative agents. PMID- 22073598 TI - [Drug sensitivity of causative agents in ocular infection of external adnexa and anterior segments--multicenter study of causative agents and drug sensitivity of ocular infection by the Japanese Association for Ocular Infection part II]. AB - PURPOSE: To report the drug sensitivity of causative agents produced by ocular infection of external adnexa and anterior segments investigated by the nationwide survey conducted by Japanese Association for Ocular Infection between September, 2007 and August, 2008. SUBJECTS AND METHODS: Among all strains isolated, causative and presumed causative agents were selected according to the criteria described, and drug sensitivity tests were conducted by minimum inhibitory concentrations (MIC) with 10 kinds of antimicrobial agents including 5 fluoroquinolones. RESULTS: Among 281 causative isolates, cefmenoxime (CMX) showed the highest sensitivity, followed by fluoroquinolones. Staphylococci and Streptococci were more sensitive to fluoroquinolones when compared to the others. Haemophilus influenzae was very sensitive to all fluoroquinolones. Corynebacterium spp. and Propionibacterium acnes were most sensitive to CMX and erythromycin respectively. CONCLUSION: CMX and fluoroquinolones showed generally good sensitivity among causative pathogens of ocular infection. PMID- 22073599 TI - [Cost-effectiveness of ranibizumab, photodynamic therapy and pegaptanib sodium in the treatment of neovascular age-related macular degeneration in Japanese]. AB - PURPOSE: To perform cost-utility analysis of ranibizumab, photodynamic therapy (PDT) and pegaptanib sodium treatment of neovascular age-related macular degeneration (AMD) with subfoveal choroidal neovascularization. MATERIALS AND METHODS: The analyses were performed on a 75-year old man with the starting visual acuity of letter score of 50 on an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart, with the affected eye having better sight than the contralateral eye, for the time horizons of 1 and 11 year (s). Visual acuity data from the large controlled studies for ranibizumab, photodynamic therapy and pegaptanib sodium, were applied. The results were compared with best supportive care (BSC) data. Cost indications included direct medical costs and costs related with social blindness. Utility values were estimated from the time trade off method. This analysis was performed from a societal perspective. RESULTS: In the 1-year model, cost of treatment was dominant in the treatment groups, whereas the cost of blindness was dominant in the BSC. In the 11-year model, influence of cost of blindness resulted in the increasing costs for BSC. Of note, ranibizumab and PDT were less costly and showed an increase in utility compared to the BSC. Pegaptanib sodium was found to be costly. Sensitivity analysis found that the results were robust to changes in various model parameters. CONCLUSION: In the current model, ranibizumab and PDT confer quality-adjusted life years (QALY) gains and are less costly compared to BSC in the lifetime treatment. In contrast, pegaptanib sodium treatment could be considered to be of minimal cost effectiveness. Ranibizumab and PDT confer excellent value in the models of the lifetime treatment. PMID- 22073600 TI - [Comparison of vitrectomy outcomes for eyes with proliferative vitreoretinopathy with and without prior vitrectomy]. AB - PURPOSE: To compare the surgical outcomes of vitrectomy for eyes with proliferative vitreoretinopathy (PVR) with and without prior vitrectomy. METHODS: Eighty-two eyes of 81 patients (35 women and 46 men), who underwent vitrectomy for grade C PVR and had at least 6 months of follow-up, were studied retrospectively. The mean age of the cases was 50.8 years (range; 8-84 years). Twenty-eight eyes had undergone prior vitrectomy (vitrectomized group) and 54 eyes had no prior vitrectomy (primary vitrectomy group). The intraoperative technique of vitreous surgery, number of vitrectomy procedures, surgical success rate, visual acuity and intraocular pressure before and 6 months after the vitrectomy of the two groups were compared. RESULTS: The rate of the anterior (type 4 and 5) PVR cases was significantly higher in the vitrectomized group than in the primary vitrectomy group (p = 0.028), whereas the rate of the only subretinal cases (type 3) PVR was significantly higher in the primary vitrectomy group (p<0.001). There were no significant differences in the preoperative visual acuity and intraocular pressure between the two groups. The rate of the cases who underwent retinotomy/retinectomy was significantly higher (p< 0.001)in the vitrectomized group than in the primary vitrectomy group. The surgical success rate and postoperative visual acuity were significantly better in the primary vitrectomy group than in the vitrectomized group (p = 0.040, <0.001, respectively). The postoperative intraocular pressure was significantly lower (p = 0.017) in the vitrectomized group than in the primary vitrectomy group, and the rate of the cases with hypotony of less than 5mmHg was significantly higher (p<0.001) in the vitrectomized group than in the primary vitrectomy group. CONCLUSIONS: Compared to the PVR eyes that had had no prior vitrectomy, the PVR eyes that underwent prior vitrectomy had a significantly higher rate of complications of anterior PVR and a significantly higher rate of retinotomy/retinectomy, leading to a significantly poorer surgical outcomes. PMID- 22073601 TI - [Relationship between the frequency of disc hemorrhage and the enlargement of nerve fiber layer defects and the deterioration speed of visual field loss in normal-tension glaucoma with wedge-shaped nerve fiber layer defects]. AB - PURPOSE: To examine progressive visual field loss in relation to disc hemorrhage (DH) and enlarged nerve fiber layer defects (NFLDs) in normal-tension glaucoma (NTG). SUBJECTS AND METHODS: There were 106 eyes of 106 NTG patients (mean follow up: 9.1 years) with well-defined NFLD borders and at least 3 years of follow-up. Examination was performed on their rate of visual field loss (MD slope and hemifield TD slope) and their rate of NFLD angle enlargement. For the NFLD angle, we took color fundus photographs and converted color photos into black-white photos extracted the blue ingredient. The midpoint between the fovea and the disc center was determined. The center was established as the disc, and the distance to the midpoint was established as the radius of a circle. The NFLD angle was defined as the angle formed by the two points where this circle intersected the NFLD and a third point which was the disc center. RESULTS: DH was seen in 51/106 (48.1%)cases and it occurred 1.28 +/- 1.99 times. In the DH group, the MD slope was -0.30 dB/year, indicating a significantly faster rate of visual field loss than that of the non-DH group (-0.13 dB/year); the rate of NFLD enlargement was 1.90 degrees/year, indicating a significantly faster rate than that of the non-DH group at 0.64 degrees/year. As the occurrence of DH increased, the TD slope (r = 0.263, p = 0.0056) and the rate of NFLD enlargement (r = 0.410, p<0.0001) increased significantly. CONCLUSION: Examination was performed on NTG eyes with well-defined NFLD borders which were divided into the groups of with and without DH. The DH eyes had a faster rate of NFLD enlargement and faster progression of visual field loss compared with the non-DH eyes. In addition, the rate of NFLD enlargement and progression of visual field loss increased in the cases with frequent DHs. PMID- 22073602 TI - [Multicenter clinical study of bone-anchored hearing aids in Japan--application for congenital auricular atresia]. AB - The effectiveness of bone anchored hearing aid (BAHA) for the patients with congenital aural atresia was evaluated by multicenter clinical study in Japan. Twenty patients (17 bilateral and 3 hemilateral) of congenital auricular atresia were registered for this study and finally, 18 of them (15 bilateral and 3 unilateral) were subjected to further evaluation. Primary endpoint of this study was free sound-field pure-tone audiometory and speech threshold hearing test in quiet and noisy circumstances. Secondary endpoint of this study was patient's satisfaction based upon APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire survey. These results were compared between before and 12 weeks after BAHA surgery. Both hearing level of pure tone and speech threshold significantly improved after BAHA surgery. APHAB scores also suggested the improvement of the QOL after BAHA usage, except for the scores that concerned with unpleasantness of noisy sound. BAHA is one of the useful options for the treatment of congenital auricular atresia. PMID- 22073603 TI - [A case of Schneiderian middle-ear and sinonasal papilloma with intracranial complications]. AB - Unlike Schneiderian papilloma, a widespread benign epithelial neoplasm arising in the sinonasal tract mucosa of the nasal cavity, paranasal sinus, trachea, and larynx, middle-ear Schneiderian papilloma is extremely rare. We report a case of recurrent Schneiderian papilloma spreading to the bilateral middle ear and right paranasal sinus, and eventually causing cerebellar complications. A-52-year old woman seen for episodes of inarticulateness was first, found to have middle right ear and right ethmoid papilloma, that occurred thereafter is the middle left ear. This bilateral middle-ear papilloma is, to our knowledge, the only case reported thus far, and fell into a low-risk malignant formation group based on HPV-DNA testing. Given previous cases, we concluded that ours warranted meticulous follow up because recurrence and malignancy are more common in multiple-site middle-ear papilloma as in our case rather than papilloma of the middle ear alone. PMID- 22073604 TI - [Nonspecific IgE potential in nasal discharge for diagnosing allergic rhinitis]. AB - Given that the nasal discharge of subjects with allergic rhinitis contains IgE, we studied nonspecific IgE potential in nasal discharge as a diagnostic marker for allergic rhinitis. We divided 38 adults into 2 groups, one with 22 with Japanese cedar pollinosis and one with 16 with watery rhinorrhea negative to MAST33. The pollinosis group was exposed to Japanese cedar pollen in an environmental exposure unit, and eosinophils in nasal discharge, serum total IgE, pollen-specific IgE, and local IgE in nasal discharge were examined for the 2 groups to determine IgE levels in nasal discharge using the Allerwatch rapid test. In the pollinosis group, nasal discharge IgE correlated significantly with the number of eosinophils. The nasal discharge IgE had higher specificity than the eosinophil examination, whereas nasal discharge eosinophils had higher sensitivity than the IgE examination. We thus found that measuring IgE and eosinophils in nasal discharge is useful for clinically diagnosing allergic rhinitis. PMID- 22073605 TI - [Analysis of predominant bacterial species and clinical backgrounds in lung abscess patients]. AB - We reviewed the clinicopathological characteristics of lung abscesses retrospectively. We analyzed 89 patients hospitalized from July 1984 to May 2009. Most were men (76/89). There were large proportions with alcohol consumption (29.2%) and dental caries or gingivitis (60.7%). Furthermore, those without other diseases accounted for only 13.5%. Predominant infectious species were clear in 43 cases (48.3%) including identification of bacteria. The identification rate of predominant bacteria improved from 38.5% to 56.0% after initiation of the introduction of expectoration culture, bronchoscopic specimen collection and gingival culture in 2003, facilitating clarification of the predominant bacteria. The Streptococcus anginosus group with predominant bacteria being slightly aerobic streptococci, anaerobic bacterium, and aerobic bacterium was detected in 10, 12, and 31 cases, respectively. The improvement in the identification rate of predominant bacteria was achieved by carrying out examination with close liaison with the staff of our inspection room. In selecting antimicrobials based on diagnostic significance, we should focus on positive identification of predominant bacteria, a factor which appears to have major clinical significance. PMID- 22073606 TI - [The origin of frequency dependence of respiratory resistance: airflow simulation study by the use of a 4D pulmonary lobule model]. AB - BACKGROUND AND OBJECTIVE: The origin of frequency dependence of respiratory resistance has been explained by ventilation inhomogeneity, however it is unclear which components in the respiratory system generate the frequency dependence. The author constructed a 4D pulmonary lobule model and analyzed relationships between airflow rate, pressure and airway resistance by the use of computational fluid dynamics (CFD). METHODS: The lobule model contained bifurcated bronchioles with two adjacent acini in which deformable inter-acinar septa and alveolar duct walls were designed. Constrictive conditions of respective bronchioles were designed, too. 4D finite element models for CFD were generated and airflow simulations were performed under moving boundary conditions of the arbitrary Lagrangean-Eulerean method. From the simulation results, airway resistances for various conditions were calculated. RESULTS: Tissue resistance emerged under the condition of different acinar pressures caused by unequal airway resistances. If the inter acinar septum was shifted so as to cancel the pressure difference, the acinar pressures were equal in spite of unequal airway resistances, and hence, tissue resistances did not emerge. Therefore, the tissue resistance in the former case is thought to be an index of alveolar pressure inequality (which could be canceled by mechanical interaction of lung parenchyma), rather than a material property of the tissue itself. CONCLUSIONS: Inequality of alveolar pressure decreases as the input oscillatory frequency increases. Therefore, frequency dependence of the respiratory resistance should be regarded as a conditional index of the alveolar pressure inequality caused by heterogeneous changes in the intra-pulmonary airway and/or the lung parenchyma. PMID- 22073607 TI - [A case of microscopic polyangiitis with silicosis]. AB - A 76-year-old man was admitted to our hospital because of increasing size of lung nodules, while he was under observation for silicosis at another hospital. As the result of bronchoscopic biopsy, it was confirmed that they were silicotic nodules. However, he was hospitalized again about one month later due to left spontaneous pneumothorax. The pneumothorax improved immediately by persistent drainage of the thoracic cavity, but he developed a fever on day 9, and ground glass opacities in both lungs also became exacerbated in spite of our administration of antibiotics. In addition, the level of MPO-ANCA increased markedly and multiple 3-10mm sized purpurae was seen on the right thigh on day 29. Skin biopsy specimens revealed infiltration of histiocytes and lymphocytes around medium-sized vessels in lower dermis. We diagnosed microscopic polyangiitis, then treated with steroid and immunosuppressive therapy. Fever and radiological findings improved significantly from the day after initiation of steroid administration. The patient was discharged on day 92 because of the improvement of his respiratory condition. We report a case of microscopic polyangiitis with silicosis, which markedly improved by steroid and immunosuppressive therapy. PMID- 22073608 TI - [A case of Churg-Strauss syndrome with subarachnoid hemorrhage and left phrenic nerve paralysis]. AB - A 60-year-old woman was given a diagnosis of Churg-Strauss syndrome (CSS) in 2000 because of peripheral blood eosinophilia, eosinophilic pneumonia, asthma, polyarticular pain, and limb numbness. She was treated with prednisolone (PSL), and the above symptoms improved but then relapsed on tapering of PSL. In September 2009, after 7 days of tapering of PSL to 5mg/day, the patient developed a subarachnoid hemorrhage and was admitted. MRA and cerebral angiography revealed no aneurysm; the source of bleeding could not be determined, but her symptoms indicated a benign course. A chest X-ray 27 days after admission showed left diaphragmatic elevation, and left phrenic nerve paralysis was diagnosed by a phrenic nerve stimulation test. Peripheral blood eosinophilia had progressed gradually during the admission period, and although it is rare for subarachnoid hemorrhage and phrenic nerve paralysis to be associated with CSS, we regarded these as vasculitis symptoms related to CSS. PMID- 22073609 TI - [A Good syndrome associated with pure red cell aplasia]. AB - A 78-year-old woman was admitted because of persistent cough, fever and sputum for one week. She had been treated with radiation therapy for inoperable thymoma complicated by severe heart failure and had been suffering from recurrent pneumonia and otitis media since then. A chest radiograph on admission showed an anterior mediastinal mass shadow and infiltrates in the bilateral lower lung fields. Serum gamma globulin was decreased and erythroid cells in the bone marrow were markedly decreased. Thymoma with hypogammaglobulinemia is called Good syndrome. We reported this very rare case of Good syndrome. After improving the infection, cyclosporine A was administered for PRCA and hypo-gamma globulinemia, but we discontinued this due to liver dysfunction. We have been currently continuing her treatment with red blood cell transfusion and immunoglobulin supplement only. PMID- 22073610 TI - [A case of Legionnaires' pneumonia accompanied by clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) with transient altered mental status and cerebellar symptoms, which responded to treatment by antibiotics and corticosteroid]. AB - A 60-year-old man was admitted because of fever, headache, and difficulty in walking. Respiratory symptoms included only mild cough, but crackles were present on auscultation at the right lung base, the chest roentgenogram and computed tomography scans showed consolidation in the right lower lobe. Laboratory findings revealed hyponatremia, elevated liver function test values and creatine phosphokinase, and Legionella pneumophila antigen in urine. Neurological examination revealed mild mental status change, dysmetria, dysarthria, and ataxic gait. Diffusion-weighted magnetic resonance imaging (MRI) of the brain, performed at the time of admission, revealed regions of high intensity in the splenium corpus callosum. We diagnosed Legionnaires' pneumonia accompanied by clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), and started treatment with ciprofloxacin and methylprednisolone at 1 mg/kg/day. Neurological symptoms gradually improved. On day 6 after admission, mild dysarthria and ataxic gait remained, a 123-IMP single photon emission computed tomography revealed no abnormality. On day 15 after admission, the only neurological symptom was mild ataxic gait; the MRI scans showed no abnormalities. On day 29 after admission, neurological symptoms were completely resolved. This is the first reported case of Legionnaires' pneumonia accompanied by clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) was treated with not only antibiotics but also corticosteroid. PMID- 22073611 TI - [A case of pulmonary benign metastasizing leiomyoma from the uterus]. AB - We report here a case of pulmonary benign metastasizing leiomyoma (BML) from the uterus. A 48-year-old woman was admitted to our hospital because of multiple pulmonary nodules on the chest radiograph 7 years after total hysterectomy with removal of the left ovarium for uterine leiomyoma. A specimen of the lesion obtained by a thoracoscopic lung biopsy was consistent with leiomyoma. Histological re-evaluation of the uterine myoma showed similar histology as compared with the lung tumor. Immunohistological staining for both estrogen and progesterone receptors on the lung tissue was positive. Based on these results, we diagnosed the pulmonary lesions as BML. The patient received no treatment and has shown no evidence of exacerbation of disease during 6 years of follow up. PMID- 22073612 TI - [A case of cutaneous vasculitis caused by erlotinib treatment and a review of literature]. AB - Erlotinib is a potent drug used for treating epidermal growth factor receptor (EGFR) mutation positive lung cancer. In this study, we report a case of erlotinib induced cutaneous vasculitis. The patient was a 69-year-old woman with a history of left lower lobe resection for lung cancer. Two years after the resection, she had metastasis in the adrenal glands for which we initiated erlotinib therapy at a dose of 150 mg/day. The patient developed multiple purpurae with a partially necrotic region on both lower thighs at 8 weeks after initiating therapy. The skin biopsy results revealed cutaneous vasculitis. We stopped erlotinib therapy after this diagnosis because of this adverse effect as well as because it exacerbated the cancer. The patient's skin manifestation disappeared 2 weeks after stopping therapy, with no recurrence of any symptoms of systemic vasculitis. We reviewed the literature on drug-induced vasculitis due to oral EGFR inhibitors and found 13 such cases. In most cases, the symptoms appeared 1-2 months after initiating therapy. In all the cases, the symptoms resolved within 2-6 weeks after stopping drug therapy. Erlotinib-induced cutaneous vasculitis is rare but may cause fatal systemic vasculitis. Therefore, the skin of patients who are undergoing erlotinib therapy should be carefully examined at regular intervals during the course of therapy for drug-induced adverse effects. PMID- 22073613 TI - [Two cases of juvenile-onset and adult-onset recurrent respiratory papillomatosis]. AB - We recently experienced one each of 2 types of recurrent respiratory papillomatosis (RRP). Case 1 (juvenile-onset type): A 30-year-old woman presenting with bloody sputum and large tumors with cavities on her chest Xray film, was referred to our hospital. She had been diagnosed with laryngeal papillomatosis when she was three years old. According to our bronchoscopical examination biopsy, she was diagnosed with squamous cell carcinoma of the lung in addition to papillomatosis of the trachea and bronchus. Although chemotherapy was performed, she died 2 years after the diagnosis of lung cancer without any distinct treatment efficacy. Case 2 (adult-onset type): A 43 year-old woman presenting with fever and dry cough visited our hospital. Chest CT revealed that there was narrowing of bilateral main bronchi and hilar lymphadenopathy. Bronchoscopic examination revealed diffuse papilloma distributed extensively from the trachea to bilateral main bronchi. However, she recovered spontaneously in 6 months and has remained stable without recurrence. Both cases were diagnosed with RRP based on the separation of HPV in case 1 and pathological findings of koilocytosis in case 2. Case 1 was complicated with squamous cell carcinoma of the lung in the clinical course, presumably due to occurrence of malignant conversion of papillomatosis. Since RRP is a rare but refractory disease, novel effective treatment is necessary. PMID- 22073614 TI - [A case of myocarditis associated with polymyositis preceded by interstitial pneumonia]. AB - A 33-year old man was admitted to our hospital because of an abnormal shadow on the chest radiograph, dry cough, and exertional dyspnea. Chest radiograph and high-resolution computed tomography (HRCT) on admission showed ground-glass opacities and bronchiectasis with volume loss in the bilateral dorsal areas. Thoracoscopic lung biopsy specimens showed mainly a pattern of NSIP (nonspecific interstitial pneumonia). We considered this case as hypersensitivity pneumonia or interstitial pneumonia (IP) associated with collagen disease. Oral prednisolone (PSL) was initiated at 55 mg/day (1 mg/kg). However he complained of proximal muscle weakness and pain and difficulty of breathing. He had heart failure due to the myocarditis. We established a diagnosis of IP associated with polymyositis and it was confirmed by his symptoms, muscle biopsy findings and elevation of serum CPK. We considered this case as the myocarditis due to polymyositis. PMID- 22073615 TI - [Pulmonary tumor thrombotic microangiopathy responding to chemotherapy]. AB - A 65-year-old man without a history of cancer presented to our hospital because he was suspected of having acute pulmonary thromboembolism. Dyspnea that had developed 1 month before admission, had worsened 1-week before admission. Chest computed tomography showed faint ground-glass opacities in the lung fields without filling defects in the pulmonary arteries. He was transferred to the department of respiratory medicine for further investigation. Perfusion scintigraphy showed multiple, small perfusion defects throughout both lungs, and laboratory data showed increased lactic dehydrogenase value and thrombocytopenia. We suspected intravascular lymphoma, and a bone marrow aspiration smear detected malignant cells. We started chemotherapy on a diagnosis of intravascular lymphoma, which resulted in remarkable improvement of respiratory failure and pulmonary hypertension. After that, further evaluation of bone marrow specimen with immunostaining, the malignant cells were found not to be lymphoma cells but cancer cells. The primary site of the cells was not found by further investigation. Because of improvement of oxygenation and pulmonary hypertension, we performed transbronchial lung biopsy and diagnosed pulmonary tumor thrombotic microangiopathy. Here, we report this case and review previous reports. PMID- 22073616 TI - [A case of drug-induced pneumonitis caused by saikokeishikankyoto]. AB - We report a case of drug-induced pneumonitis caused by saikokeishikankyoto. A 68 year-old woman was admitted to our hospital complaining of dry cough, fever, and dyspnea after taking saikokeishikankyoto for 16 days. A chest radiograph showed widespread ground-glass shadows in both lung fields. Chest CT showed ground-glass opacities and thickening of the interlobular septum in both lung fields. Bronchoalveolar lavage fluids and transbronchial lung biopsy specimen showed findings consistent with drug-induced pneumonitis, therefore we diagnosed drug induced pneumonitis caused by saikokeishikankyoto. Three years previously she had suffered from a similar illness after taking hangeshashinto. Ougon is suspected to be a causative component for her saikokeishikankyoto-induced pneumonitis, because it has been reported to be as a main cause for kampo-induced pneumonitis. PMID- 22073617 TI - [A case of pyogenic spondylitis mimicking spinal invasion of lung cancer]. AB - A 65-year-old man who had suffered from traumatic spinal cord injury had chronic lumbar pain. He had exacerbation of lumbar pain and intermittent fever and consulted several doctors, but the cause of the lumbar pain was unknown. An orthopedic specialist took an MRI. Spinal MRI showed increased signal intensity at the level of T10-11 and a mass in his right lower lung field, so he was referred to our hospital. Two transbronchial lung biopsy procedures failed to obtain malignant cells. CT guided biopsy showed fibrous and hyalinizing tissue contained plasma cells and lyphocytes. Staphylococcus aureus was cultured from the second bronchial lavage fluids of brush and blood cultures, so we began administration of ampicillin-sulbactam. Avoiding threatened or actual cord compression due to collapse resulting from spinal instability, posterior fusion with instrumentation was done through the back of his chest wall. At once, bone biopsy was done, and showed no malignant cells. As soon as antibacterial treatment was stopped after the operation, he had bloody sputa and fever. The antibacterial agent was resumed and the symptoms improved. The mass decreased in size and lumbar pain improved gradually, so we concluded the diagnosis was pyogenic spondylitis caused by S. aureus. After about 5 months of antibacterial treatment, the tumor substantially diminished. PMID- 22073618 TI - [A relapse of small-cell lung cancer ten years after concomitant chemoradiotherapy followed by high-dose chemotherapy with autologous peripheral blood stem cell transfusion]. AB - A 57-year-old man had limited-disease small cell lung cancer in the left lower lobe of the lung. He was treated with chemotherapy with concurrent accelerated hyperfractionated thoracic radiation, followed by high-dose chemotherapy with autologous peripheral blood stem cell transplantation. He had obtained a complete response for 10 years until the tumor in the left lower lobe was detected by positron emission tomography. Bronchoscopic brushing cytology revealed small cell cancer, which was considered to be local relapse by staging work-up. He achieved a partial response with chemotherapy consisting of cisplatin and irinotecan. The progression-free survival rate at 5 years in limited-disease small cell lung cancer ranges from 10% to 25%. Although it was difficult to distinguish the relapse of lung cancer from second primary lung cancer, we considered this case as relapse because the tumor had the same cytology in the same lobe as the previous primary tumor. The residual cells refractory to concomitant chemoradiotherapy followed by high-dose chemotherapy with stem cell transplantation had survived and proliferated after 10 years. PMID- 22073619 TI - [A case of intractable pneumothorax in a patient with pulmonary adenocarcinoma during bevacizumab-containing chemotherapy]. AB - The patient was a 70-year-old woman. She was admitted to our hospital complaining of fever and dyspnea. Chest CT scan showed a 50 x 30-mm tumorous shadow in S6 of the left lung and honeycomb lung in both lower lobes. As the result of cytodiagnosis with ultrasonic echo, adenocarcinoma was diagnosed. Clinical stage was IIIA (T3N2M0). We selected carboplatin and paclitaxel with bevacizumab as first-line chemotherapy, but at 7 days after the initiating it, the chest X-ray showed left pneumothorax. A chest drainage tube was placed in the left thoracic cavity. The patient was treated repeatedly pleurodesis with minocycline and OK 432. The pneumothorax required 3 weeks to cure. We selected carboplatin and paclitaxel without bevacizumab for the second course, and the pneumothorax did not recur. Pneumothorax was a serious adverse event associated with bevacizumab containing chemotherapy. It is necessary to be aware of the possibility of pneumothorax when we treat lung adenocarcinoma with bevacizumab-containing chemotherapy. PMID- 22073620 TI - [Reversed halo sign in organizing pneumonia secondary to Sjogren syndrome]. AB - We report a case of a 41-year-old woman admitted to our hospital for dyspnea on exertion and nonproductive cough. High-resolution computed tomography (HRCT) revealed central ground-glass opacities surrounded by ring-shaped areas of consolidation (reversed halo sign), predominantly in the lower lobes. Bronchoalveolar lavage fluid revealed an increase of the total number of cells (35 x 10(4)/ml), including elevated lymphocyte level (69%) and decreased CD4/CD8 ratio (0.45). Histopathological examination by transbronchial lung biopsy showed polypoid masses of granulation tissue filling the lumens of a respiratory bronchiole and alveolar ducts, consistent with organizing pneumonia. After admission the patient complained of dry eyes and dry mouth. The serum anti-SS-A antibody level was also elevated (65.0 U/ml). Labial salivary gland biopsy specimens revealed focal lymphocytic infiltration of more than 50 per 4 mm(2). There were no findings of rheumatoid arthritis or other collagen diseases. We diagnosed primary Sjogren syndrome with secondary organizing pneumonia with a reversed halo sign. She was treated with prednisolone (0.5 mg/kg body weight, 35 mg/day). After treatment, the chest CT showed improvement through consolidation. PMID- 22073621 TI - [A new method for evaluating lung age]. AB - BACKGROUND AND OBJECTIVE: As part of the enlightenment campaign for COPD and for the introduction of an easy method to assess aging phenomena in respiratory function, the indicator of lung age has been suggested by the JRS Lung-Age-Spread Promotion Secretariat (original method). In this original method, the lung age was estimated by counting back the regression formula predicting the reference value of FEV1. Since the normal value of FEV1 at a given age is not unique and exists within a certain range defined as the 95% confidence limit, the backward value of lung age calculated with the original method includes various statistical and physiological problems. In the present study, I proposed a novel method allowing estimation of lung age, in which the problems related to the original method were significantly overcome. RESULTS AND CONCLUSIONS: Since the 95% confidence limit of FEV1 was not considered in the original method, the lung age of a person with high FEV1 beyond the upper end of the 95% confidence limit would result in the subject being classified as remarkably young (sometimes, the calculated lung age is below zero), while that of a person with reduced FEV1 below the lower end of the 95% confidence limit would be estimated as being very elderly (sometimes, the calculated age is over 100). On the other hand, the novel method reasonably deliberates the 95% confidence limit, leading to the conclusion that it could be applied for estimating the lung age of persons having a wide range of FEV1. PMID- 22073622 TI - [Chronological evaluation of physical, psychological and social health of urban elderly dwellers over 6 years and assessment of causal inter-relationships]. AB - OBJECTIVES: The purpose of this study is to make a chronological evaluation over 6 years of physical, psychological and social health of urban elderly dwellers. METHODS: A questionnaire survey was conducted with all urban elderly dwellers of 65 years old or more in A City in September, 2001. Answers were obtained from 13,195 people (response rate of 80.2%) in the first survey. Then 3 year and 6 year follow-up surveys of 2,375 members were performed in September 2004 and 2007. Causal relationships were analyzed using a Structural Equation Model based on the Cross-Lagged Effects Variation Model. RESULTS: According to this research, a chronological six year trend in ADL (Activities of Daily Living) was found for "physical factor" (" " means latent variable) as an observed variable, with a shifted from 91.0% to 82.9%. A trend for self-rated health with healthy as an observed variable of "psychological factor" was similarly apparent, shifting from 85.4% to 77.0%. "Social factor" conducted on the follow-up survey in 2007 was significantly affected by the "psychological factor" investigated in 2001 and "physical factor" in the follow-up survey in 2004, indirectly based on the Cross Lagged Effects Variation Model. "Social factor" totals of 25% for men and 19% for women were explained by this model with high validity levels (NFI = 0.935, IFI = 0.950, RMSEA = 0.036). CONCLUSION: It was suggested that social health was affected by psychological health directly and physical health indirectly during six years follow-up of urban elderly dwellers. Future research is needed to encompass other generations and also to improve the external validity of the results. PMID- 22073623 TI - [Condom use staging and correlations among gay and bisexual men. A questionnaire survey of Osaka gay bar customers]. AB - OBJECTIVES: This study aimed to clarify stages of condom use among gay and bisexual men at gay bars in Osaka and to assess relationships between condom use stage and attitudes and norms regarding HIV prevention. METHODS: In this cross sectional study, a self-administered survey was distributed to gay bar customers in Osaka in 2005. Completed surveys were received through the mail. Participants were divided into five groups based on condom use with regular and casual partners: pre-contemplation; contemplation; preparation; action; and maintenance. These five groups were merged into three groups: precontemplation; contemplation/preparation; and action/maintenance. Associations between these three groups of condom use stage and correlates were assessed. RESULTS: Among the 601 respondents (response rate, 44.9%), data from 546 men with lifetime sexual experience with men were used. Regarding stage distribution, the highest percentage of participants was in the pre-contemplation stage with a regular partner, and in the maintenance stage with casual partners. Activities of "MASH Osaka", a gay non-governmental organization, were widely recognized across all stages. The feeling of being unable to tell a partner to use a condom if the partner resisted condom use, being in a long-term relationship, difficulty using condoms when under the influence of drugs or alcohol, and self-efficacy all correlated with condom use stages. CONCLUSION: This study clarified condom use stages and correlations among gay and bisexual men at gay bars in Osaka. More research is needed to assess the reliability and validity of these scale items. Monitoring stage distributions and correlations with stages will be useful to evaluate HIV prevention activities. PMID- 22073624 TI - [Transition of the maternal and child health handbook system and the significance of public health administration]. PMID- 22073625 TI - [Possession rate and comments on a pamphlet containing information on pediatric emergencies for parents]. AB - OBJECTIVES: To establish an effective distribution method and necessary content for a pamphlet on pediatric emergencies for parents and guardians of kindergarteners by studying the possession rate of a pamphlet and impressions and opinions about its content. METHODS: The number of subjects was 269. The pamphlet was delivered via kindergartens to parents and guardians; two months later, an anonymous questionnaire was sent inquiring about their possession rate and impressions and opinions about the content of the pamphlet. The A6 20-page all color pamphlet (designed by the author) comprised questions regarding their decision to take their children to the hospital for 6 symptoms (fever, seizures, vomiting, diarrhea, cough, and abdominal pain), knowledge about physical assessment methods and homecare methods for children, and the phone numbers and URLs of "24-hour emergency lines for children." RESULTS: The number of valid responses was 111 (41.3%) (mean age: 36.0 +/- 4.50), with 74 (66.7%) retaining the pamphlet. There were significant differences in their experiences of illness in their children (P < 0.05) between the possession group and disposed of group, the percentage being higher in the former. Among the subjects who retained the pamphlet, 67 (90.5%) had read through it. Among them, 51 subjects (76.1%) answered that it had useful pages, and 63 subjects (94.0%) answered that they would use it in the future. Out of the information provided, including the 6 symptoms, frequently asked questions, records, and a list of phone numbers and URLs, the most useful information according to them was "a list of phone numbers and URLs" (28/54.9%), followed by "the decision to take the children to the hospital for fever" (24/47.1%) and "frequently asked questions" (21/41.2%). The possession rate was significantly higher in subjects who had experienced sudden illnesses in CONCLUSION: their children. Therefore, the likelihood of the pamphlet being retained and used would be higher if delivered to parents and guardians with children of an age more susceptible to sudden illnesses. Furthermore, many respondents chose "a list of phone numbers and URLs" as the most useful information. Therefore, a pamphlet that demonstrates how necessary information can be easily obtained and used may be more practical than one containing all the information. PMID- 22073626 TI - [Municipal housing support for people with mental disabilities to facilitate transition from an institutional to community setting]. AB - OBJECTIVES: The study investigated the provision of support by municipalities to assist people with mental disability securing a dwelling in the community. METHODS: In September 2008, a questionnaire was sent to welfare divisions concerned with people having mental disabilities in 1,805 municipalities nationwide. Responses were returned from 1,141 municipalities (recovery rate: 63.2%). The survey analyzed housing support, financial aid, understanding of transition and housing needs and recognition concerning health and welfare. RESULTS: Of those municipalities surveyed: 7.0% had a support system for those lacking a guarantor to sign a lease; 17.7% engaged in reducing the burden involved in securing a dwelling, mainly by setting up a housing advisory desk; and 5.0% worked with real-estate agents and housing providers to advance cooperation. Housing benefits were provided in 12.9% of municipalities for those living on welfare, with a special allowance equivalent to that for the physically challenged. Financial support such as funding to cover the rent and other relevant expenses was available in 2.5%. The number of people with mental disabilities seeking to make the transition to community living and the actual state of transition were not known in 52.9% of the municipalities; however, 64.9% considered that the amenities of a dwelling for such people should be comparable to those for the single-person household and the general public. Furthermore, 41.4% took actions to redress the negative images of people with mental disabilities held by the community residents. The assessment of policy regarding transition and housing support for people with mental disabilities revealed that 48.6% of municipalities considered a congregate living setting within the community, while acknowledgement of an independent living setting within the general neighborhood was low at 28.9%. Regarding the state of inter-ministerial collaboration between the welfare division for people with disabilities and other divisions, 25.5% indicated that support was provided in partnership with agencies beyond the immediate scope of health and welfare. CONCLUSION: A framework for the provision of municipality-managed transition and housing support for people with mental disability has yet to be fully developed on a national scale. A comprehensive policy regarding housing support is needed. PMID- 22073627 TI - Amplifying the benefits of agroecology by using the right cultivars. AB - Tropical soils are particularly vulnerable to fertility losses due to their low capacity to retain organic matter and mineral nutrients. This urges the development of new agricultural practices to manage mineral nutrients and organic matter in a more sustainable way while relying less on fertilizer inputs. Two methods pertaining to ecological engineering and agroecology have been tested with some success: (1) the addition of biochar to the soil, and (2) the maintenance of higher earthworm densities. However, modern crop varieties have been selected to be adapted to agricultural practices and to the soil conditions they lead to and common cultivars might not be adapted to new practices. Using rice as a model plant, we compared the responsiveness to biochar and earthworms of five rice cultivars with contrasted selection histories. These cultivars had contrasted responsivenesses to earthworms, biochar, and the combination of both. The mean relative increase in grain biomass, among all treatments and cultivars, was 94% and 32%, respectively, with and without fertilization. Choosing the best combination of cultivar and treatment led to a more than fourfold increase in this mean benefit (a 437% and a 353% relative increase in grain biomass, respectively, with and without fertilization). Besides, the more rustic cultivar, a local landrace adapted to diverse and difficult conditions, responded the best to earthworms in terms of total biomass, while a modern common cultivar responded the best in term of grain biomass. This suggests that cultivars could be selected to amplify the benefit of biochar- and earthworm-based practices. Overall, selecting new cultivars interacting more closely with soil organisms and soil heterogeneity could increase agriculture sustainability, fostering the positive feedback loop between soils and plants that has evolved in natural ecosystems. PMID- 22073628 TI - Nitrate production and availability in residential soils. AB - The rapid increase in residential land area in the United States has raised concern about water pollution associated with nitrogen fertilizers. Nitrate (NO3 ) is the form of reactive N that is most susceptible to leaching and runoff; thus, a more thorough understanding of nitrification and NO3(-) availability is needed if we are to accurately predict the consequences of residential expansion for water quality. In particular, there have been few assessments of how the land use history, housing density, and age of residential soils influence NO3(-) pools and fluxes, especially at depth. In this study, we used 1 m deep soil cores to evaluate potential net nitrification and mineralization, microbial respiration and biomass, and soil NO3(-) and NH4+ pools in 32 residential home lawns that differed by previous land use and age, but had similar soil types. These were compared to eight forested reference sites with similar soils. Our results suggest that a change to residential land use has increased pools and production of reactive N, which has clear implications for water quality in the region. However, the results contradict the common assumption that NO3(-) production and availability is dramatically higher in residential soils than in forests in general. While net nitrification (128.6 +/- 15.5 mg m(-2) d(-1) vs. 4.7 +/- 2.3 mg m(-2) d(-1); mean +/- SE) and exchangeable NO3(-) (3.8 +/- 0.5 g/m2 vs. 0.7 +/ 0.3 g/m2) were significantly higher in residential soils than in forest soils in this study, these measures of NO3(-) production and availability were still notably low, comparable to deciduous forest stands in other studies. A second unexpected result was that current homeowner management practices were not predictive of NO3(-) availability or production. This may reflect the transient availability of inorganic N after fertilizer application. Higher housing density and a history of agricultural land use were predictors of greater NO3(-) availability in residential soils. If these factors are good predictors across a wider range of sites, they may be useful indicators of NO3(-) availability and leaching and runoff potential at the landscape scale. PMID- 22073629 TI - Changes in hydrology and salinity accompanying a century of agricultural conversion in Argentina. AB - Conversions of natural woodlands to agriculture can alter the hydrologic balance, aquifer recharge, and salinity of soils and groundwater in ways that influence productivity and sustainable land use. Using a land-use change chronosequence in semiarid woodlands of Argentina's Espinal province, we examined the distribution of moisture and solutes and estimated recharge rates on adjacent plots of native woodlands and rain-fed agriculture converted 6-90 years previously. Soil coring and geoelectrical profiling confirmed the presence of spatially extensive salt accumulations in dry woodlands and pervasive salt losses in areas converted to agriculture. A 1.1-km-long electrical resistivity transect traversing woodland, 70-year-old agriculture, and woodland, for instance, revealed a low-resistivity (high-salinity) horizon between approximately 3 m and 13 m depth in the woodlands that was virtually absent in the agricultural site because of leaching. Nine meter-deep soil profiles indicated a 53% increase in soil water storage after 30 or more years of cultivation. Conservative groundwater-recharge estimates based on chloride tracer methods in agricultural plots ranged from approximately 12 to 45 mm/yr, a substantial increase from the <1 mm/yr recharge in dry woodlands. The onset of deep soil moisture drainage and increased recharge led to >95% loss of sulfate and chloride ions from the shallow vadose zone in most agriculture plots. These losses correspond to over 100 Mg of sulfate and chloride salts potentially released to the region's groundwater aquifers through time with each hectare of deforestation, including a capacity to increase groundwater salinity to >4000 mg/L from these ions alone. Similarities between our findings and those of the dryland salinity problems of deforested woodlands in Australia suggest an important warning about the potential ecohydrological risks brought by the current wave of deforestation in the Espinal and other regions of South America and the world. PMID- 22073630 TI - Potential shifts in dominant forest cover in interior Alaska driven by variations in fire severity. AB - Large fire years in which >1% of the landscape burns are becoming more frequent in the Alaskan (USA) interior, with four large fire years in the past 10 years, and 79 000 km2 (17% of the region) burned since 2000. We modeled fire severity conditions for the entire area burned in large fires during a large fire year (2004) to determine the factors that are most important in estimating severity and to identify areas affected by deep-burning fires. In addition to standard methods of assessing severity using spectral information, we incorporated information regarding topography, spatial pattern of burning, and instantaneous characteristics such as fire weather and fire radiative power. Ensemble techniques using regression trees as a base learner were able to determine fire severity successfully using spectral data in concert with other relevant geospatial data. This method was successful in estimating average conditions, but it underestimated the range of severity. This new approach was used to identify black spruce stands that experienced intermediate- to high-severity fires in 2004 and are therefore susceptible to a shift in regrowth toward deciduous dominance or mixed dominance. Based on the output of the severity model, we estimate that 39% (approximately 4000 km2) of all burned black spruce stands in 2004 had <10 cm of residual organic layer and may be susceptible a postfire shift in plant functional type dominance, as well as permafrost loss. If the fraction of area susceptible to deciduous regeneration is constant for large fire years, the effect of such years in the most recent decade has been to reduce black spruce stands by 4.2% and to increase areas dominated or co-dominated by deciduous forest stands by 20%. Such disturbance-driven modifications have the potential to affect the carbon cycle and climate system at regional to global scales. PMID- 22073631 TI - Temporal variability of forest fires in eastern Amazonia. AB - Widespread occurrence of fires in Amazonian forests is known to be associated with extreme droughts, but historical data on the location and extent of forest fires are fundamental to determining the degree to which climate conditions and droughts have affected fire occurrence in the region. We used remote sensing to derive a 23-year time series of annual landscape-level burn scars in a fragmented forest of the eastern Amazon. Our burn scar data set is based on a new routine developed for the Carnegie Landsat Analysis System (CLAS), called CLAS-BURN, to calculate a physically based burn scar index (BSI) with an overall accuracy of 93% (Kappa coefficient 0.84). This index uses sub-pixel cover fractions of photosynthetic vegetation, non-photosynthetic vegetation, and shade/burn scar spectral end members. From 23 consecutive Landsat images processed with the CLAS BURN algorithm, we quantified fire frequencies, the variation in fire return intervals, and rates of conversion of burned forest to other land uses in a 32 400 km2 area. From 1983 to 2007, 15% of the forest burned; 38% of these burned forests were subsequently deforested, representing 19% of the area cleared during the period of observation. While 72% of the fire-affected forest burned only once during the 23-year study period, 20% burned twice, 6% burned three times, and 2% burned four or more times, with the maximum of seven times. These frequencies suggest that the current fire return interval is 5-11 times more frequent than the estimated natural fire regime. Our results also quantify the substantial influence of climate and extreme droughts caused by a strong El Nino Southern Oscillation (ENSO) on the extent and likelihood of returning forest fires mainly in fragmented landscapes. These results are an important indication of the role of future warmer climate and deforestation in enhancing emissions from more frequently burned forests in the Amazon. PMID- 22073632 TI - No evidence that chronic nitrogen additions increase photosynthesis in mature sugar maple forests. AB - Atmospheric nitrogen (N) deposition can increase forest growth. Because N deposition commonly increases foliar N concentrations, it is thought that this increase in forest growth is a consequence of enhanced leaf-level photosynthesis. However, tests of this mechanism have been infrequent, and increases in photosynthesis have not been consistently observed in mature forests subject to chronic N deposition. In four mature northern hardwood forests in the north central United States, chronic N additions (30 kg N ha(-1) yr(-1) as NaNO3 for 14 years) have increased aboveground growth but have not affected canopy leaf biomass or leaf area index. In order to understand the mechanism behind the increases in growth, we hypothesized that the NO3(-) additions increased foliar N concentrations and leaf-level photosynthesis in the dominant species in these forests (sugar maple, Acer saccharum). The NO3(-) additions significantly increased foliar N. However, there was no significant difference between the ambient and +NO3(-) treatments in two seasons (2006-2007) of instantaneous measurements of photosynthesis from either canopy towers or excised branches. In measurements on excised branches, photosynthetic nitrogen use efficiency (micromol CO2 s(-1) g(-1) N) was significantly decreased (-13%) by NO3(-) additions. Furthermore, we found no consistent NO3(-) effect across all sites in either current foliage or leaf litter collected annually throughout the study (1993-2007) and analyzed for delta 13C and delta 18O, isotopes that can be used together to integrate changes in photosynthesis over time. We observed a small but significant NO3(-) effect on the average area and mass of individual leaves from the excised branches, but these differences varied by site and were countered by changes in leaf number. These photosynthesis and leaf area data together suggest that NO3(-) additions have not stimulated photosynthesis. There is no evidence that nutrient deficiencies have developed at these sites, so unlike other studies of photosynthesis in N-saturated forests, we cannot attribute the lack of a stimulation of photosynthesis to nutrient limitations. Rather than increases in C assimilation, the observed increases in aboveground growth at our study sites are more likely due to shifts in C allocation. PMID- 22073633 TI - The influence of land use and climate change on forest biomass and composition in Massachusetts, USA. AB - Land use and climate change have complex and interacting effects on naturally dynamic forest landscapes. To anticipate and adapt to these changes, it is necessary to understand their individual and aggregate impacts on forest growth and composition. We conducted a simulation experiment to evaluate regional forest change in Massachusetts, USA over the next 50 years (2010-2060). Our objective was to estimate, assuming a linear continuation of recent trends, the relative and interactive influence of continued growth and succession, climate change, forest conversion to developed uses, and timber harvest on live aboveground biomass (AGB) and tree species composition. We examined 20 years of land use records in relation to social and biophysical explanatory variables and used regression trees to create "probability-of-conversion" and "probability-of harvest" zones. We incorporated this information into a spatially interactive forest landscape simulator to examine forest dynamics as they were affected by land use and climate change. We conducted simulations in a full-factorial design and found that continued forest growth and succession had the largest effect on AGB, increasing stores from 181.83 Tg to 309.56 Tg over 50 years. The increase varied from 49% to 112% depending on the ecoregion within the state. Compared to simulations with no climate or land use, forest conversion reduced gains in AGB by 23.18 Tg (or 18%) over 50 years. Timber harvests reduced gains in AGB by 5.23 Tg (4%). Climate change (temperature and precipitation) increased gains in AGB by 17.3 Tg (13.5%). Pinus strobus and Acer rubrum were ranked first and second, respectively, in terms of total AGB throughout all simulations. Climate change reinforced the dominance of those two species. Timber harvest reduced Quercus rubra from 10.8% to 9.4% of total AGB, but otherwise had little effect on composition. Forest conversion was generally indiscriminate in terms of species removal. Under the naive assumption that future land use patterns will resemble the recent past, we conclude that continued forest growth and recovery will be the dominant mechanism driving forest dynamics over the next 50 years, and that while climate change may enhance growth rates, this will be more than offset by land use, primarily forest conversion to developed uses. PMID- 22073634 TI - Assessing effects of land use on landscape connectivity: loss and fragmentation of western U.S. forests. AB - Effects of land-use change on the conservation of biodiversity have become a concern to conservation scientists and land managers, who have identified loss and fragmentation of natural areas as a high-priority issue. Despite urgent calls to inform national, regional, and state planning efforts, there remains a critical need to develop practical approaches to identify where important lands are for landscape connectivity (i.e., linkages), where land use constrains connectivity, and which linkages are most important to maintain network-wide connectivity extents. Our overall goal in this paper was to develop an approach that provides comprehensive, quantitative estimates of the effects of land-use change on landscape connectivity and illustrate its use on a broad, regional expanse of the western United States. We quantified loss of habitat and landscape connectivity for western forested systems due to land uses associated with residential development, roads, and highway traffic. We examined how these land use changes likely increase the resistance to movement of forest species in non forested land cover types and, therefore, reduce the connectivity among forested habitat patches. To do so, we applied a graph-theoretic approach that incorporates ecological aspects within a geographic representation of a network. We found that roughly one-quarter of the forested lands in the western United States were integral to a network of forested patches, though the lands outside of patches remain critical for habitat and overall connectivity. Using remotely sensed land cover data (ca. 2000), we found 1.7 million km2 of forested lands. We estimate that land uses associated with residential development, roads, and highway traffic have caused roughly a 4.5% loss in area (20 000 km2) of these forested patches, and continued expansion of residential land will likely reduce forested patches by another 1.2% by 2030. We also identify linkages among forest patches that are critical for landscape connectivity. Our approach can be readily modified to examine connectivity for other habitats/ecological systems and for other geographic areas, as well as to address more specific requirements for particular conservation planning applications. PMID- 22073635 TI - Transient dynamics of invasive competition: barred owls, spotted owls, habitat, and the demons of competition present. AB - The recent range expansion of Barred Owls (Strix varia) into the Pacific Northwest, where the species now co-occurs with the endemic Northern Spotted Owl (Strix occidentalis caurina), resulted in a unique opportunity to investigate potential competition between two congeneric, previously allopatric species. The primary criticism of early competition research was the use of current species' distribution patterns to infer past processes; however, the recent expansion of the Barred Owl and the ability to model the processes that result in site occupancy (i.e., colonization and extinction) allowed us to address the competitive process directly rather than inferring past processes through current patterns. The purpose of our study was to determine whether Barred Owls had any negative effects on occupancy dynamics of nesting territories by Northern Spotted Owls and how these effects were influenced by habitat characteristics of Spotted Owl territories. We used single-species, multi-season occupancy models and covariates quantifying Barred Owl detections and habitat characteristics to model extinction and colonization rates of Spotted Owl pairs in southern Oregon, USA. We observed a strong, negative association between Barred Owl detections and colonization rates and a strong positive effect of Barred Owl detections on extinction rates of Spotted Owls. We observed increased extinction rates in response to decreased amounts of old forest at the territory core and higher colonization rates when old-forest habitat was less fragmented. Annual site occupancy for pairs reflected the strong effects of Barred Owls on occupancy dynamics with much lower occupancy rates predicted for territories where Barred Owls were detected. The strong Barred Owl and habitat effects on occupancy dynamics of Spotted Owls provided evidence of interference competition between the species. These effects increase the importance of conserving large amounts of contiguous, old-forest habitat to maintain Northern Spotted Owls in the landscape. PMID- 22073636 TI - When conservation management becomes contraindicated: impact of food supplementation on health of endangered wildlife. AB - Understanding the conditions that force the implementation of management actions and their efficiency is crucial for conservation of endangered species. Wildlife managers are widely and increasingly using food supplementation for such species because the potentially immediate benefits may translate into rapid conservation improvements. Supplementary feeding can also pose risks eventually promoting undesired, unexpected, subtle, or indirect, and often unnoticed, effects that are generally poorly understood. For two decades, intensive food supplementation has been used in attempting to improve the breeding productivity of the Spanish Imperial Eagle, Aquila adalberti, one of the most endangered birds of prey in the world. Here, we examined the impact of this intensive management action on nestling health, including contamination, immunodepression, and acquisition of disease agents derived from supplementation techniques and provisioned food. Contrary to management expectations, we found that fed individuals were often inadvertently "medicated" with pharmaceuticals (antibiotics and antiparasitics) contained in supplementary food (domestic rabbits). Individuals fed with medicated rabbits showed a depressed immune system and a high prevalence and richness of pathogens compared with those with no or safe supplementary feeding using non-medicated wild rabbits. A higher presence of antibiotics (fluoroquinolones) was found in sick as opposed to healthy individuals among eaglets with supplementary feeding, which points directly toward a causal effect of these drugs in disease and other health impairments. This study represents a telling example of well-meaning management strategies not based on sound scientific evidence becoming a "contraindicated" action with detrimental repercussions undermining possible beneficial effects by increasing the impact of stochastic factors on extinction risk of endangered wildlife. PMID- 22073637 TI - Quantifying the importance of patch-specific changes in habitat to metapopulation viability of an endangered songbird. AB - A growing number of programs seek to facilitate species conservation using incentive-based mechanisms. Recently, a market-based incentive program for the federally endangered Golden-cheeked Warbler (Dendroica chrysoparia) was implemented on a trial basis at Fort Hood, an Army training post in Texas, USA. Under this program, recovery credits accumulated by Fort Hood through contracts with private landowners are used to offset unintentional loss of breeding habitat of Golden-cheeked Warblers within the installation. Critical to successful implementation of such programs is the ability to value, in terms of changes to overall species viability, both habitat loss and habitat restoration or protection. In this study, we sought to answer two fundamental questions: Given the same amount of change in breeding habitat, does the change in some patches have a greater effect on metapopulation persistence than others? And if so, can characteristics of a patch (e.g., size or spatial location) be used to predict how the metapopulation will respond to these changes? To answer these questions, we describe an approach for using sensitivity analysis of a metapopulation projection model to predict how changes to specific habitat patches would affect species viability. We used a stochastic, discrete-time projection model based on stage-specific estimates of survival and fecundity, as well as various assumptions about dispersal among populations. To assess a particular patch's leverage, we quantified how much metapopulation viability was expected to change in response to changing the size of that patch. We then related original patch size and distance from the largest patch to each patch's leverage to determine if general patch characteristics could be used to develop guidelines for valuing changes to patches within a metapopulation. We found that both the characteristic that best predicted patch leverage and the magnitude of the relationship changed under different model scenarios. Thus, we were unable to find a consistent set of relationships, and therefore we emphasize the dangers in relying on general guidelines to assess patch value. Instead, we provide an approach that can be used to quantitatively evaluate patch value and identify critical needs for future research. PMID- 22073638 TI - Estimating age from recapture data: integrating incremental growth measures with ancillary data to infer age-at-length. AB - Estimating the age of individuals in wild populations can be of fundamental importance for answering ecological questions, modeling population demographics, and managing exploited or threatened species. Significant effort has been devoted to determining age through the use of growth annuli, secondary physical characteristics related to age, and growth models. Many species, however, either do not exhibit physical characteristics useful for independent age validation or are too rare to justify sacrificing a large number of individuals to establish the relationship between size and age. Length-at-age models are well represented in the fisheries and other wildlife management literature. Many of these models overlook variation in growth rates of individuals and consider growth parameters as population parameters. More recent models have taken advantage of hierarchical structuring of parameters and Bayesian inference methods to allow for variation among individuals as functions of environmental covariates or individual-specific random effects. Here, we describe hierarchical models in which growth curves vary as individual-specific stochastic processes, and we show how these models can be fit using capture-recapture data for animals of unknown age along with data for animals of known age. We combine these independent data sources in a Bayesian analysis, distinguishing natural variation (among and within individuals) from measurement error. We illustrate using data for African dwarf crocodiles, comparing von Bertalanffy and logistic growth models. The analysis provides the means of predicting crocodile age, given a single measurement of head length. The von Bertalanffy was much better supported than the logistic growth model and predicted that dwarf crocodiles grow from 19.4 cm total length at birth to 32.9 cm in the first year and 45.3 cm by the end of their second year. Based on the minimum size of females observed with hatchlings, reproductive maturity was estimated to be at nine years. These size benchmarks are believed to represent thresholds for important demographic parameters; improved estimates of age, therefore, will increase the precision of population projection models. The modeling approach that we present can be applied to other species and offers significant advantages when multiple sources of data are available and traditional aging techniques are not practical. PMID- 22073639 TI - Invasive competitor and native seed predators contribute to rarity of the narrow endemic Astragalus sinuatus Piper. AB - The conservation of rare plant species hinges on our ability to identify the underlying mechanisms that limit rare plant populations. Theory on rarity suggests that both predispersal seed predation and competition can be important mechanisms influencing abundance and/or distribution of rare plant populations. Yet few studies have tested these interactions, and those that have evaluated each mechanism independently. Astragalus sinuatus Piper (Whited's milkvetch) is a narrow endemic plant species restricted to eight populations within a 10-km2 area in eastern Washington. We used experimental and observational methods to test the effects of native insect predispersal seed predators and an invasive grass (Bromus tectorum L. [cheatgrass]) on seed set and population density of A. sinuatus. We quantified per capita seed production and pod predation rates across four sites and among four years. Seed predation rates were high across four sites (66-82%) and all years (65-82%). Experimental reduction of predispersal seed predators significantly increased per capita seed set of A. sinuatus (164-345%) at two experimental sites. Concurrently, two seed addition experiments demonstrated the effect of seed loss and presence of B. tectorum on seedling recruitment and establishment of A. sinuatus over four growing seasons. In the first seed addition experiment, we found no difference in recruitment and establishment between low (40) and high (120) seed addition levels. In the second addition experiment (one level of addition; 40 seeds), we found that recruitment and survivorship increased 200% in plots where B. tectorum was removed compared to plots where B. tectorum was present. Thus, seed addition had no impact in the presence of B. tectorum; conversely, in the absence of B. tectorum, seed addition was highly effective at increasing population numbers. Results suggest that, in areas where B. tectorum is present, recruitment is site limited, and it is seed limited when B. tectorum is absent. We recommend that managers reduce B. tectorum in an effort to increase population growth of A. sinuatus; in areas where B. tectorum is absent, short-term reduction of insect predators should be considered as a strategy to increase population growth of this rare species. PMID- 22073640 TI - Metapopulation dynamics in the butterfly Hipparchia semele changed decades before occupancy declined in The Netherlands. AB - The survival of many species in human-dominated, fragmented landscapes depends on metapopulation dynamics, i.e., on a dynamic equilibrium of extinctions and colonizations in patches of suitable habitat. To understand and predict distributional changes, knowledge of these dynamics can be essential, and for this, metapopulation studies are preferably based on long-time-series data from many sites. Alas, such data are very scarce. An alternative is to use opportunistic data (i.e., collected without applying standardized field methods), but these data suffer from large variations in field methods and search intensity between sites and years. Dynamic site-occupancy models offer a general approach to adjust for variable survey effort. These models extend classical metapopulation models to account for imperfect detection of species and yield estimates of the probabilities of occupancy, colonization, and survival of species at sites. By accounting for detection, they fully correct for among-year variability in search effort. As an illustration, we fitted a dynamic site occupancy model to 60 years of presence-absence data (more precisely, detection nondetection) of the heathland butterfly Hipparchia semele in The Netherlands. Detection records were obtained from a database containing volunteer-based data from 1950-2009, and nondetection records were deduced from database records of other butterfly species. Our model revealed that metapopulation dynamics of Hipparchia had changed decades before the species' distribution began to contract. Colonization probability had already started to decline from 1950 onward, but this was counterbalanced by an increase in the survival of existing populations, the result of which was a stable distribution. Only from 1990 onward was survival not sufficient to compensate for the further decrease of colonization, and occupancy started to decline. Hence, it appears that factors acting many decades ago triggered a change in the metapopulation dynamics of this species, which ultimately led to a severe decline in occupancy that only became apparent much later. Our study emphasizes the importance of knowledge of changes in survival and colonization of species in modern landscapes over a very long time scale. It also demonstrates the power of site-occupancy modeling to obtain important population dynamics information from databases containing opportunistic sighting records. PMID- 22073641 TI - Effects of chytrid fungus and a glyphosate-based herbicide on survival and growth of wood frogs (Lithobates sylvaticus). AB - Anthropogenic-derived stressors in the environment, such as contaminants, are increasingly considered important cofactors that may decrease the immune response of amphibians to pathogens. Few studies, however, have integrated amphibian disease and contaminants to test this multiple-stressor hypothesis for amphibian declines. We examined whether exposure to sublethal concentrations of a glyphosate-based herbicide and two strains of the pathogenic chytrid fungus, Batrachochrytrium dendrobatidis (Bd) could: (1) sublethally affect wood frogs (Lithobates sylvaticus) by altering the time to and size at metamorphosis, and (2) directly affect survivability of wood frogs after metamorphosis. Neither Bd strain nor herbicide exposure alone significantly altered growth or time to metamorphosis. The two Bd strains did not differ in their pathogenicity, and both caused mortality in post-metamorphic wood frogs. There was no evidence of an interaction between treatments, indicating a lack of herbicide-induced susceptibility to Bd. However, the trends in our data suggest that exposure of wood frogs to a high concentration of glyphosate-based herbicide may reduce Bd caused mortality compared to animals exposed to Bd alone. These results exemplify the complexities inherent when populations are coping with multiple stressors. In this case, the perceived stressor, glyphosate-based herbicide, appeared to affect the pathogen more than the host's immune system, relieving the host from disease caused effects. This suggests caution when invoking multiple stressors as a cause for increased disease susceptibility and indicates that the effects of multiple stressors on disease outcome depend on the interrelationships of stressors to both the pathogen and the host. PMID- 22073642 TI - Predicting breeding habitat for amphibians: a spatiotemporal analysis across Yellowstone National Park. AB - The ability to predict amphibian breeding across landscapes is important for informing land management decisions and helping biologists better understand and remediate factors contributing to declines in amphibian populations. We built geospatial models of likely breeding habitats for each of four amphibian species that breed in Yellowstone National Park (YNP). We used field data collected in 2000-2002 from 497 sites among 16 basins and predictor variables from geospatial models produced from remotely sensed data (e.g., digital elevation model, complex topographic index, landform data, wetland probability, and vegetative cover). Except for 31 sites in one basin that were surveyed in both 2000 and 2002, all sites were surveyed once. We used polytomous regression to build statistical models for each species of amphibian from (1) field survey site data only, (2) field data combined with data from geospatial models, and (3) data from geospatial models only. Based on measures of receiver operating characteristic (ROC) scores, models of the second type best explained likely breeding habitat because they contained the most information (ROC values ranged from 0.70 to 0.88). However, models of the third type could be applied to the entire YNP landscape and produced maps that could be verified with reserve field data. Accuracy rates for models built for single years were highly variable, ranging from 0.30 to 0.78. Accuracy rates for models built with data combined from multiple years were higher and less variable, ranging from 0.60 to 0.80. Combining results from the geospatial multiyear models yielded maps of "core" breeding areas (areas with high probability values for all three years) surrounded by areas that scored high for only one or two years, providing an estimate of variability among years. Such information can highlight landscape options for amphibian conservation. For example, our models identify alternative areas that could be protected for each species, including 6828-10 764 ha for tiger salamanders, 971-3017 ha for western toads, 4732-16 696 ha for boreal chorus frogs, and 4940-19 690 ha for Columbia spotted frogs. PMID- 22073643 TI - Quantitative recommendations for amphibian terrestrial habitat conservation derived from habitat selection behavior. AB - Conservation scientists have noted that conservation managers rarely use scientific information when making decisions. One of the reasons why managers rarely use scientific information may be that conservation scientists rarely provide their knowledge in a way that can directly be used by conservation practitioners. Here we show how quantitative recommendations for conservation can be derived. Previous research on terrestrial habitat selection behavior of toads (Bufo bufo and Bufo viridis) showed that wood deposits are a key resource in the terrestrial habitat. We used habitat-dependence analysis to estimate the amount of this key resource, wood deposits, that individual toads require. Based on these estimates we then quantify the requirements for wood deposits for a population. Additionally, we quantified the area that a population requires. Although wood deposits vary strongly in size, we found little evidence for size preferences: only one species preferred smallest sizes of wood deposits. We report all the estimates in a way that can be directly used by conservation managers. Habitat-dependence analysis is a simple and useful tool to quantify habitat requirements. Provisioning of wood deposits may improve the quality of terrestrial habitat for amphibians. Thereby, managers may increase the carrying capacity of terrestrial habitats and support elevated population densities. PMID- 22073644 TI - The effects of regional angling effort, angler behavior, and harvesting efficiency on landscape patterns of overfishing. AB - We used a coupled social-ecological model to study the landscape-scale patterns emerging from a mobile population of anglers exploiting a spatially structured walleye (Sander vitreus) fishery. We systematically examined how variations in angler behaviors (i.e., relative importance of walleye catch rate in guiding fishing site choices), harvesting efficiency (as implied by varying degrees of inverse density-dependent catchability of walleye), and angler population size affected the depletion of walleye stocks across 157 lakes located near Thunder Bay (Ontario, Canada). Walleye production biology was calibrated using lake specific morphometric and edaphic features, and angler fishing site choices were modeled using an empirically grounded multi-attribute utility function. We found support for the hypothesis of sequential collapses of walleye stocks across the landscape in inverse proportionality of travel cost from the urban residence of anglers. This pattern was less pronounced when the regional angler population was low, density-dependent catchability was absent or low, and angler choices of lakes in the landscape were strongly determined by catch rather than non-catch related attributes. Thus, our study revealed a systematic pattern of high catch importance reducing overfishing potential at low and aggravating overfishing potential at high angler population sizes. The analyses also suggested that density-dependent catchability might have more serious consequences for regional overfishing states than variations in angler behavior. We found little support for the hypotheses of systematic overexploitation of the most productive walleye stocks and homogenized catch-related qualities among lakes sharing similar access costs to anglers. Therefore, one should not expect anglers to systematically exploit the most productive fisheries or to equalize catch rates among lakes through their mobility and other behaviors. This study underscores that understanding landscape overfishing dynamics involves a careful appreciation of angler population size and how it interacts with the attributes that drive angler behaviors and depensatory mechanisms such as inverse density-dependent catchability. Only when all of these ingredients are considered and understood can one derive reasonably predictable patterns of overfishing in the landscape. These patterns range from self-regulating systems with low levels of regional fishing pressure to sequential collapse of walleye fisheries from the origin of angling effort. PMID- 22073645 TI - Influence of behavior and mating success on brood-specific contribution to fish recruitment in ponds. AB - One source of uncertainty in predicting the response of populations to exploitation is individual differences within a population in both vulnerability to capture and contribution to population renewal. For species with parental care, individuals engaged in nesting behavior are often targeted for exploitation, but predicting outcomes of this nonrandom vulnerability will depend in part on an understanding of how parental traits are related to potential for brood contribution to the population. Variation in brood-specific contribution to recruitment of largemouth bass (Micropterus salmoides), a fish species with extended parental care, was quantified to determine if differences in mating success, parental care behaviors, and timing of reproduction influenced offspring recruitment. Dependence of these relationships on brood predation was tested in communities that differed in the presence of bluegill, Lepomis macrochirus, an important nest predator. Daily snorkel surveys were conducted in experimental ponds during spring to monitor male spawning and parental care behaviors in populations of largemouth bass. Tissue samples collected from larvae in nests were used to develop brood-specific DNA fingerprints for determining nest origins of fall recruits. Largemouth bass spawning period in bluegill ponds was longer and more variable in duration, with lower, more variable mating success, than in ponds without bluegill. In all populations, only one or two broods provided the majority of recruits, and these were broods produced during the earliest days of spawning by the oldest, largest males. In bluegill ponds, brood contribution from earliest nests also increased with brood size. Earliest nesters were the oldest males, and recruits from these nests were often above average in body size. Offspring needed to be guarded to at least swim-up larval stage to contribute any recruits. Termination of parental protection before offspring were free swimming mainly occurred with broods guarded by smaller males in ponds with brood predators. These age- and size-specific differences in timing of spawning and duration of parental care are consistent with influences of residual reproductive value and energetic constraints on reproductive behavior. Furthermore, these patterns of individual contribution to recruitment imply that fisheries that selectively target either nesting individuals or larger, older males could potentially decrease recruitment at the population scale. PMID- 22073646 TI - Assessing ecosystem vulnerability to invasive rusty crayfish (Orconectes rusticus). AB - Despite the widespread introduction of nonnative species and the heterogeneity of ecosystems in their sensitivity to ecological impacts, few studies have assessed ecosystem vulnerability to the entire invasion process, from arrival to establishment and impacts. Our study addresses this challenge by presenting a probabilistic, spatially explicit approach to predicting ecosystem vulnerability to species invasions. Using the freshwater-rich landscapes of Wisconsin, USA, we model invasive rusty crayfish (Orconectes rusticus) as a function of exposure risk (i.e., likelihood of introduction and establishment of O. rusticus based on a species distribution model) and the sensitivity of the recipient community (i.e., likelihood of impacts on native O. virilis and O. propinquus based on a retrospective analysis of population changes). Artificial neural networks predicted that approximately 10% of 4200 surveyed lakes (n = 388) and approximately 25% of mapped streams (23 523 km total length) are suitable for O. rusticus introduction and establishment. A comparison of repeated surveys before vs. post-1985 revealed that O. virilis was six times as likely and O. propinquus was twice as likely to be extirpated in streams invaded by O. rusticus, compared to streams that were not invaded. Similarly, O. virilis was extirpated in over three-quarters of lakes invaded by O. rusticus compared to half of the uninvaded lakes, whereas no difference was observed for O. propinquus. We identified 115 lakes (approximately 3% of lakes) and approximately 5000 km of streams (approximately 6% of streams) with a 25% chance of introduction, establishment, and extirpation by O. rusticus of either native congener. By identifying highly vulnerable ecosystems, our study offers an effective strategy for prioritizing on the-ground management action and informing decisions about the most efficient allocation of resources. Moreover, our results provide the flexibility for stakeholders to identify priority sites for prevention efforts given a maximum level of acceptable risk or based on budgetary or time restrictions. To this end, we incorporate the model predictions into a new online mapping tool with the intention of closing the communication gap between academic research and stakeholders that requires information on the prospects of future invasions. PMID- 22073647 TI - Spatial connectivity in a large river system: resolving the sources and fate of dissolved organic matter. AB - Large rivers are generally heterogeneous and productive systems that receive important inputs of dissolved organic matter (DOM) from terrestrial and in situ sources. Thus, they are likely to play a significant role in the biogeochemical cycling of the DOM flowing to the oceans. The asymmetric spatial gradient driven by directional flow and environmental heterogeneity contributes to the fate of DOM flowing downstream. Yet, the relative effects of spatial connectivity and environmental heterogeneity on DOM dynamics are poorly understood. For example, since environmental variables show spatial heterogeneity, the variation explained by environmental and spatial variables may be redundant. We used the St. Lawrence River (SLR) as a representative large river to resolve the unique influences of environmental heterogeneity and spatial connectivity on DOM dynamics. We used three-dimensional fluorescence matrices combined with parallel factor analysis (PARAFAC) to characterize the DOM pool in the SLR. Seven fluorophores were modeled, of which two were identified to be of terrestrial origin and three from algal exudates. We measured a set of environmental variables that are known to drive the fate of DOM in aquatic systems. Additionally, we used asymmetric eigenvector map (AEM) modeling to take spatial connectivity into account. The combination of spatial and environmental models explained 85% of the DOM variation. We show that spatial connectivity is an important driver of DOM dynamics, as a large fraction of environmental heterogeneity was attributable to the asymmetric spatial gradient. Along the longitudinal axis, we noted a rapid increase in dissolved organic carbon (DOC), mostly controlled by terrestrial input of DOM originating from the tributaries. Variance partitioning demonstrated that freshly produced protein-like DOM was found to be the preferential substrate for heterotrophic bacteria undergoing rapid proliferation, while humic-like DOM was more correlated to the diffuse attenuation coefficient of UVA radiation. PMID- 22073648 TI - Denitrification mitigates N flux through the stream-floodplain complex of a desert city. AB - The Indian Bend Wash (IBW) flood-control project relies on a greenbelt to carry floods through Scottsdale, Arizona, USA. The greenbelt is characterized by a chain of shallow artificial lakes in a larger floodplain of irrigated turf, which has been protected from encroaching urban development. As such, this urban stream floodplain complex can be divided into three subsystems: artificial lakes, channelized stream segments, and floodplain. We conducted experiments to evaluate which, if any, of these subsystems were important sites of denitrification, and to explore factors controlling denitrification rates. Denitrification enzyme activity (DEA) bioassays were conducted on sediments from eight lake and six stream segments as well as soil samples from eight floodplain transects. Mass specific potential denitrification rates were significantly higher in lakes than in streams or floodplains. Nutrient limitation bioassays revealed that nitrate (NO3-) limited denitrification in lake sediments, a surprising finding given that NO3(-)-rich groundwater additions frequently raised lake NO3(-) concentration above 1 mg N/L. Experiments on intact lake cores suggested that denitrification was limited by the rate NO3(-) diffused into sediments, rather than its availability in overlying water. Floodplain denitrification was limited by water content, not NO3(-) or C, and irrigation of soils stimulated denitrification. We constructed a N budget for the IBW stream-floodplain complex based on our experimental results. We found that both lakes and floodplains removed large quantities of N, with denitrification removing 261 and 133 kg N ha(-1) yr(-1) from lake sediments and floodplain soils, respectively, indicating that lakes are hotspots for denitrification. Nevertheless, because floodplain area was >4.5 times that of lakes, floodplain soils removed nearly 2.5 times as much N as lake sediments. Given the desert's low annual precipitation, a finding that floodplain soils are active sites of denitrification might seem implausible; however, irrigation is common in urban landscapes, and it elevated annual denitrification in IBW. Based on our results, we conclude that construction of artificial lakes created hotspots while application of irrigation water created hot moments for denitrification in the stream-floodplain complex, demonstrating that management decisions can improve the ability of urban streams to provide critical ecosystem services like N retention. PMID- 22073649 TI - Ecosystem services and urban heat riskscape moderation: water, green spaces, and social inequality in Phoenix, USA. AB - Urban ecosystems are subjected to high temperatures--extreme heat events, chronically hot weather, or both-through interactions between local and global climate processes. Urban vegetation may provide a cooling ecosystem service, although many knowledge gaps exist in the biophysical and social dynamics of using this service to reduce climate extremes. To better understand patterns of urban vegetated cooling, the potential water requirements to supply these services, and differential access to these services between residential neighborhoods, we evaluated three decades (1970-2000) of land surface characteristics and residential segregation by income in the Phoenix, Arizona, USA metropolitan region. We developed an ecosystem service trade-offs approach to assess the urban heat riskscape, defined as the spatial variation in risk exposure and potential human vulnerability to extreme heat. In this region, vegetation provided nearly a 25 degrees C surface cooling compared to bare soil on low-humidity summer days; the magnitude of this service was strongly coupled to air temperature and vapor pressure deficits. To estimate the water loss associated with land-surface cooling, we applied a surface energy balance model. Our initial estimates suggest 2.7 mm/d of water may be used in supplying cooling ecosystem services in the Phoenix region on a summer day. The availability and corresponding resource use requirements of these ecosystem services had a strongly positive relationship with neighborhood income in the year 2000. However, economic stratification in access to services is a recent development: no vegetation-income relationship was observed in 1970, and a clear trend of increasing correlation was evident through 2000. To alleviate neighborhood inequality in risks from extreme heat through increased vegetation and evaporative cooling, large increases in regional water use would be required. Together, these results suggest the need for a systems evaluation of the benefits, costs, spatial structure, and temporal trajectory for the use of ecosystem services to moderate climate extremes. Increasing vegetation is one strategy for moderating regional climate changes in urban areas and simultaneously providing multiple ecosystem services. However, vegetation has economic, water, and social equity implications that vary dramatically across neighborhoods and need to be managed through informed environmental policies. PMID- 22073650 TI - The interplay between environmental conditions and allee effects during the recovery of stressed zooplankton communities. AB - Many important ecological phenomena depend on the success or failure of small introduced populations. Several factors are thought to influence the fate of small populations, including resource and habitat availability, dispersal levels, interspecific interactions, mate limitation, and demographic stochasticity. Recent field studies suggest that Allee effects resulting from mate limitation can prevent the reestablishment of sexual zooplankton species following a disturbance. In this study, we explore the interplay between Allee effects and local environmental conditions in determining the population growth and establishment of two acid-sensitive zooplankton species that have been impacted by regional anthropogenic acidification. We conducted a factorial design field experiment to test the impact of pH and initial organism densities on the per capita population growth (r) of the sexual copepod Epischura lacustris and the seasonally parthenogenetic cladoceran Daphnia mendotae. In addition, we conducted computer simulations using r values obtained from our experiments to determine the probability of extinction for small populations of acid-sensitive colonists that are in the process of colonizing recovering lakes. The results of our field experiment demonstrated that local environmental conditions can moderate the impacts of Allee effects for E. lacustris: Populations introduced at low densities had a significantly lower r at pH 6 than at pH 7. In contrast, r did not differ between pH 6 and 7 environments when E. lacustris populations were introduced at high densities. D. mendotae was affected by pH levels, but not by initial organism densities. Results from our population growth simulations indicated that E. lacustris populations introduced at low densities to pH 6 conditions had a higher probability of extinction than those introduced at low densities to a pH 7 environment. Our study indicates that environmental conditions and mate limitation can interact to determine the fate of small populations of sexually reproducing zooplankton species. If a more rapid recovery of acid-damaged zooplankton communities is desired, augmentation of dispersal levels may be needed during the early phases of pH recovery in order to increase the probability of establishment for mate-limited zooplankton species. PMID- 22073652 TI - Gridded meteorological data as a resource for mechanistic macroecology in coastal environments. AB - Gridded weather data were evaluated as sources of forcing variables for biophysical models of intertidal animal body temperature with model results obtained using local weather station data serving as the baseline of comparison. The objective of the study was to determine which gridded data are sufficient to capture observed patterns of thermal stress. Three coastal sites in western North America were included in this analysis: Boiler Bay, Oregon; Bodega Bay, California; and Pacific Grove, California. The gridded data with the highest spatial resolution, the 32-km North American Regional Reanalysis (NARR) and the 38-km Climate Forecasting System Reanalysis (CFSR), predicted daily maximum intertidal animal temperature most similarly to the local weather Station data. Time step size was important for variables that change rapidly throughout the day, such as solar radiation. There were site-based differences in the ability of the model to predict daily maximum intertidal animal temperature, with the gridded data predictions being the closest to local weather station predictions in Boiler Bay, Oregon. In a review of gridded data used as part of ecological studies, there was broad use of the data across subject areas and ecosystems so the recent improvements in the spatial (from 2 degrees to 32 km) and temporal scales (from 6 hours to 1 hour) of gridded data will further add to the applicability within the ecological community particularly for mechanistic studies. PMID- 22073651 TI - Effect of temperature on biogeochemistry of marine organic-enriched systems: implications in a global warming scenario. AB - Coastal biogeochemical cycles are expected to be affected by global warming. By means of a mesocosm experiment, the effect of increased water temperature on the biogeochemical cycles of coastal sediments affected by organic-matter enrichment was tested, focusing on the carbon, sulfur, and iron cycles. Nereis diversicolor was used as a model species to simulate macrofaunal bioirrigation activity in natural sediments. Although bioirrigation rates of N. diversicolor were not temperature dependent, temperature did have a major effect on the sediment metabolism. Under organic-enrichment conditions, the increase in sediment metabolism was greater than expected and occurred through the enhancement of anaerobic metabolic pathway rates, mainly sulfate reduction. There was a twofold increase in sediment metabolism and the accumulation of reduced sulfur. The increase in the benthic metabolism was maintained by the supply of electron acceptors through bioirrigation and as a result of the availability of iron in the sediment. As long as the sediment buffering capacity toward sulfides is not surpassed, an increase in temperature might promote the recovery of organic enriched sediments by decreasing the time for mineralization of excess organic matter. PMID- 22073653 TI - Poor-data and data-poor species stock assessment using a Bayesian hierarchical approach. AB - Appropriate inference for stocks or species with low-quality data (poor data) or limited data (data poor) is extremely important. Hierarchical Bayesian methods are especially applicable to small-area, small-sample-size estimation problems because they allow poor-data species to borrow strength from species with good quality data. We used a hammerhead shark complex as an example to investigate the advantages of using hierarchical Bayesian models in assessing the status of poor data and data-poor exploited species. The hammerhead shark complex (Sphyrna spp.) along the Atlantic and Gulf of Mexico coasts of the United States is composed of three species: the scalloped hammerhead (S. lewini), the great hammerhead (S. mokarran), and the smooth hammerhead (S. zygaena) sharks. The scalloped hammerhead comprises 70-80% of the catch and has catch and relative abundance data of good quality, whereas great and smooth hammerheads have relative abundance indices that are both limited and of low quality presumably because of low stock density and limited sampling. Four hierarchical Bayesian state-space surplus production models were developed to simulate variability in population growth rates, carrying capacity, and catchability of the species. The results from the hierarchical Bayesian models were considerably more robust than those of the nonhierarchical models. The hierarchical Bayesian approach represents an intermediate strategy between traditional models that assume different population parameters for each species and those that assume all species share identical parameters. Use of the hierarchical Bayesian approach is suggested for future hammerhead shark stock assessments and for modeling fish complexes with species specific data, because the poor-data species can borrow strength from the species with good data, making the estimation more stable and robust. PMID- 22073654 TI - Estimating cyanobacterial bloom transport by coupling remotely sensed imagery and a hydrodynamic model. AB - The ability to forecast the transport of harmful cyanobacterial blooms in the Laurentian Great Lakes is beneficial to natural resource managers concerned with public health. This manuscript describes a method that improves the prediction of cyanobacterial bloom transport with the use of a preoperational hydrodynamic model and high temporal resolution satellite imagery. Two scenarios were examined from separate cyanobacterial blooms in western Lake Erie, USA. The first scenario modeled bloom position and extent over the span of 13 days. A geographic center, or centroid, was calculated and assigned to the bloom from observed satellite imagery. The bloom centroid was projected forward in time, and the projected position was compared to the final observed bloom centroid. Image pixels flagged as cyanobacterial bloom were compared between the initial image and the final image, and this was assumed as persistence. The second bloom scenario was modeled for a period of 12 days, and the results were framed in an ecological context in an effort to gain further understanding of cyanobacterial bloom dynamics. These modeling techniques can be incorporated into an operational forecasting system. PMID- 22073655 TI - A model-based approach to determine the long-term effects of multiple interacting stressors on coral reefs. AB - The interaction between multiple stressors on Caribbean coral reefs, namely, fishing effort and hurricane impacts, is a key element in the future sustainability of reefs. We develop an analytic model of coral-algal interactions and explicitly consider grazing by herbivorous reef fish. Further, we consider changes in structural complexity, or rugosity, in addition to the direct impacts of hurricanes, which are implemented as stochastic jump processes. The model simulations consider various levels of fishing effort corresponding to' several hurricane frequencies and impact levels dependent on geographic location. We focus on relatively short time scales so we do not explicitly include changes in ocean temperature, chemistry, or sea level rise. The general features of our approach would, however, apply to these other stressors and to the management of other systems in the face of multiple stressors. It is determined that the appropriate management policy, either local reef restoration or fisheries management, greatly depends on hurricane frequency and impact level. For sufficiently low hurricane impact and macroalgal growth rate, our results indicate that regions with lower-frequency hurricanes require stricter fishing regulations, whereas management in regions with higher-frequency hurricanes might be less concerned with enhancing grazing and instead consider whether local-scale restorative activities to increase vertical structure are cost-effective. PMID- 22073656 TI - Spatial surplus production modeling of Atlantic tunas and billfish. AB - We formulate and simulation-test a spatial surplus production model that provides a basis with which to undertake multispecies, multi-area, stock assessment. Movement between areas is parameterized using a simple gravity model that includes a "residency" parameter that determines the degree of stock mixing among areas. The model is deliberately simple in order to (1) accommodate nontarget species that typically have fewer available data and (2) minimize computational demand to enable simulation evaluation of spatial management strategies. Using this model, we demonstrate that careful consideration of spatial catch and effort data can provide the basis for simple yet reliable spatial stock assessments. If simple spatial dynamics can be assumed, tagging data are not required to reliably estimate spatial distribution and movement. When applied to eight stocks of Atlantic tuna and billfish, the model tracks regional catch data relatively well by approximating local depletions and exchange among high-abundance areas. We use these results to investigate and discuss the implications of using spatially aggregated stock assessment for fisheries in which the distribution of both the population and fishing vary over time. PMID- 22073657 TI - Spatial factors affecting statistical power in testing marine fauna displacement. AB - Impacts of offshore wind farms on marine fauna are largely unknown. Therefore, one commonly adheres to the precautionary principle, which states that one shall take action to avoid potentially damaging impacts on marine ecosystems, even when full scientific certainty is lacking. We implement this principle by means of a statistical power analysis including spatial factors. Implementation is based on geostatistical simulations, accommodating for zero-inflation in species data. We investigate scenarios in which an impact assessment still has to be carried out. Our results show that the environmental conditions at the time of the survey is the most influential factor on power. This is followed by survey effort and species abundance in the reference situation. Spatial dependence in species numbers at local scales affects power, but its effect is smaller for the scenarios investigated. Our findings can be used to improve effectiveness of the economical investment for monitoring surveys. In addition, unnecessary extra survey effort, and related costs, can be avoided when spatial dependence in species abundance is present and no improvement on power is achieved. PMID- 22073658 TI - Quantifying secondary pest outbreaks in cotton and their monetary cost with causal-inference statistics. AB - Secondary pest outbreaks occur when the use of a pesticide to reduce densities of an unwanted target pest species triggers subsequent outbreaks of other pest species. Although secondary pest outbreaks are thought to be familiar in agriculture, their rigorous documentation is made difficult by the challenges of performing randomized experiments at suitable scales. Here, we quantify the frequency and monetary cost of secondary pest outbreaks elicited by early-season applications of broad-spectrum insecticides to control the plant bug Lygus spp. (primarily L. hesperus) in cotton grown in the San Joaquin Valley, California, USA. We do so by analyzing pest-control management practices for 969 cotton fields spanning nine years and 11 private ranches. Our analysis uses statistical methods to draw formal causal inferences from nonexperimental data that have become popular in public health and economics, but that are not yet widely known in ecology or agriculture. We find that, in fields that received an early-season broad-spectrum insecticide treatment for Lygus, 20.2% +/- 4.4% (mean +/- SE) of late-season pesticide costs were attributable to secondary pest outbreaks elicited by the early-season insecticide application for Lygus. In 2010 U.S. dollars, this equates to an additional $6.00 +/- $1.30 (mean +/- SE) per acre in management costs. To the extent that secondary pest outbreaks may be driven by eliminating pests' natural enemies, these figures place a lower bound on the monetary value of ecosystem services provided by native communities of arthropod predators and parasitoids in this agricultural system. PMID- 22073659 TI - Indicators of ecosystem function identify alternate states in the sagebrush steppe. AB - Models of ecosystem change that incorporate nonlinear dynamics and thresholds, such as state-and-transition models (STMs), are increasingly popular tools for land management decision-making. However, few models are based on systematic collection and documentation of ecological data, and of these, most rely solely on structural indicators (species composition) to identify states and transitions. As STMs are adopted as an assessment framework throughout the United States, finding effective and efficient ways to create data-driven models that integrate ecosystem function and structure is vital. This study aims to (1) evaluate the utility of functional indicators (indicators of rangeland health, IRH) as proxies for more difficult ecosystem function measurements and (2) create a data-driven STM for the sagebrush steppe of Colorado, USA, that incorporates both ecosystem structure and function. We sampled soils, plant communities, and IRH at 41 plots with similar clayey soils but different site histories to identify potential states and infer the effects of management practices and disturbances on transitions. We found that many IRH were correlated with quantitative measures of functional indicators, suggesting that the IRH can be used to approximate ecosystem function. In addition to a reference state that functions as expected for this soil type, we identified four biotically and functionally distinct potential states, consistent with the theoretical concept of alternate states. Three potential states were related to management practices (chemical and mechanical shrub treatments and seeding history) while one was related only to ecosystem processes (erosion). IRH and potential states were also related to environmental variation (slope, soil texture), suggesting that there are environmental factors within areas with similar soils that affect ecosystem dynamics and should be noted within STMs. Our approach generated an objective, data-driven model of ecosystem dynamics for rangeland management. Our findings suggest that the IRH approximate ecosystem processes and can distinguish between alternate states and communities and identify transitions when building data driven STMs. Functional indicators are a simple, efficient way to create data driven models that are consistent with alternate state theory. Managers can use them to improve current model-building methods and thus apply state-and transition models more broadly for land management decision-making. PMID- 22073660 TI - Assessing landscape structure and pattern fragmentation in semiarid ecosystems using patch-size distributions. AB - Spatial vegetation patterns are recognized as sources of valuable information that can be used to infer the state and functionality of semiarid ecosystems, particularly in the context of both climate and land use change. Recent studies have suggested that the patch-size distribution of vegetation in drylands can be described using power-law metrics, and that these scale-free distributions deviate from power-law linearity with characteristic scale lengths under the effects of increasing aridity or human disturbance, providing an early sign of desertification. These findings have been questioned by several modeling approaches, which have identified the presence of characteristic scale lengths on the patch-size distribution of semiarid periodic landscapes. We analyze the relationship between fragmentation of vegetation patterns and their patch-size distributions in semiarid landscapes showing different degree of periodicity (i.e., banding). Our assessment is based on the study of vegetation patterns derived from remote sensing in a series of semiarid Australian Mulga shrublands subjected to different disturbance levels. We use the patch-size probability density and cumulative probability distribution functions from both nondirectional and downslope analyses of the vegetation patterns. Our results indicate that the shape of the patch-size distribution of vegetation changes with the methodology of analysis applied and specific landscape traits, breaking the universal applicability of the power-law metrics. Characteristic scale lengths are detected in (quasi) periodic banded ecosystems when the methodology of analysis accounts for critical landscape anisotropies, using downslope transects in the direction of flow paths. In addition, a common signal of fragmentation is observed: the largest vegetation patches become increasingly less abundant under the effects of disturbance. This effect also explains deviations from power-law behavior in disturbed vegetation which originally showed scale-free patterns. Overall, our results emphasize the complexity of structure assessment in dryland ecosystems, while recognizing the usefulness of the patch-size distribution of vegetation for monitoring semiarid ecosystems, especially through the cumulative probability distributions, which showed high sensitivity to fragmentation of the vegetation patterns. We suggest that preserving large vegetation patches is a critical task for the maintenance of the ecosystem structure and functionality. PMID- 22073661 TI - Ecosystem development in roadside grasslands: biotic control, plant-soil interactions, and dispersal limitations. AB - Roadside grasslands undergoing secondary succession are abundant, and represent ecologically meaningful examples of novel, human-created ecosystems. Interactions between plant and soil communities (hereafter plant-soil interactions) are of major importance in understanding the role of biotic control in ecosystem functioning, but little is known about these links in the context of ecosystem restoration and succession. The assessment of the key biotic communities and interactions driving ecosystem development will help practitioners to better allocate the limited resources devoted to roadside grassland restoration. We surveyed roadside grasslands from three successional stages (0-2, 7-9, and >20 years) in two Mediterranean regions of Spain. Structural equation modeling was used to evaluate how interactions between plants, biological soil crusts (BSCs), and soil microbial functional diversity (soil microorganisms) affect indicators of ecosystem development and restoration: plant similarity to the reference ecosystem, erosion control, and soil C storage and N accumulation. Changes in plant community composition along the successional gradient exerted the strongest influence on these indicators. High BSC cover was associated with high soil stability, and high soil microbial functional diversity from late-successional stages was associated with high soil fertility. Contrary to our expectations, the indirect effects of plants, mediated by either BSCs or soil microorganisms, were very weak in both regions, suggesting a minor role for plant-soil interactions upon ecosystem development indicators over long periods. Our results suggest that natural vegetation dynamics effectively improved ecosystem development within a time frame of 20 years in the grasslands evaluated. They also indicate that this time could be shortened if management actions focus on: (1) maintaining well conserved natural areas close to roadsides to enhance plant compositional changes towards late-successional stages, (2) increasing BSC cover in areas under strong erosion risk, to avoid soil loss, and (3) enhancing soil microbial functional diversity in resource-limited areas, to enhance soil C and N accumulation. PMID- 22073662 TI - Phosphorus flow analysis of the socioeconomic ecosystem of Shucheng County, China. AB - Human activities disturb the long-term phosphorus (P) cycle in nature, whereby the resulting intensive release of P contributes to the eutrophication of surface water. Hence, a detailed understanding of P flow as it relates to socioeconomic systems is essential for effective nutrient management. This study develops a substance-flow-analysis model for P metabolism for the socioeconomic ecosystem of Shucheng County in Anhui Province in central China as a case study. We estimate P flow using data from questionnaires, face-to-face interviews, published literature, and official statistical databases. Our results show that P flow in Shucheng's current socioeconomic system is linear and openly metabolic. The total P input into Shucheng in 2008 reached 12 748 Mg, mainly as P ores and crops. In all, 43.83% of the total P input was exported, and 30.44% was discharged into surface water. More-balanced nutrient management and options for improving nutrient use efficiency are discussed. The quantifiable, science-based methods used in this study may be applied to neighboring regions of central China for sustainable development and water management. PMID- 22073663 TI - An alternative view of ecological community thresholds and appropriate analyses for their detection: comment. PMID- 22073664 TI - [The century of noise]. AB - When did, actually, "noise pollution" begin to coexist along with our daily life and activities and change our environmental natural sounds, which hadn't changed for centuries? Industrial revolution, first, and the introduction of new technologies later, introduced "noise" as one of the most relevant features that marked the development of progress. Later on, it became the distinctive characteristic of the XX century. The incessant rumble of industrial machinery, of weapons and cannons from the wars, the roar of cars in the streets and aeroplanes from the sky, the deafening sound of XX century music, as well as the shouting out of new political ideas suddenly invaded the new century. They became part of our daily life so much as almost to become a new lay religion of modernity. As the century proceeded towards economic boom, a "new noisy Man" complied with this change, becoming the anthropologic prototype who was able to adapt to the new style of life and even contribute to its expansion. All this finally allows, to day, a definition of the XX century as the "century of noise". PMID- 22073665 TI - [Metalworking industry management evolution]. AB - Analysis of the evolution drivers of the management systems in the metalworking industry, mainly characterized as "automotive", starting with the "mass production" model, followed for the development of Italian industry in the '50. Through the socio-economic changes of the '90/10, the metalworking plants were deeply restructured with the introduction of computers in the production systems, and then with the first global benchmarks such as the "lean production", towards the needed operational flexibility to respond to the market dynamics. Plants change radically, company networks become real, ICT services are fundamental elements for the integration. These trends help visualizing a new "Factory of the Future" for the years 2020/30, where the competition will be based on the socio economical, technological and environmental factors included in the "Competitive Sustainable Manufacturing" paradigm. PMID- 22073666 TI - [Technological evolution in the manufacting industry]. AB - In this paper the 5 contemporary paradigms of the production technologies are summarised and the potential developments are examined. Further, the most advanced machining technologies are illustrated and the developments in the machine tools and in the tools that are deeply transforming the production environment, with particular reference to machining. PMID- 22073667 TI - [The present state of the clinical and epidemiologic research on chemical and carcinogenic risks in the metalworking industry]. AB - In this report several publications on clinical-epidemiologic patterns are presented regarding chemical and oncogenic risk in the metalworking industry. Sources of information were mainly PubMed and TOXNET. As far as cancer is concerned the body of the epidemiological data is difficult to interpret, mainly due to the fact that even the most recent papers and reviews refer to past exposure to MWF. Moreover, the great number of cancer sites are hardly explainable as to the biological plausibility. However, it is likely that current problems might be overcome by the almost total elimination of PAH and some additives. Moreover, cancer risk for welders and painters should be considered according to the different techniques used. Several studies reported repeated outbreaks of Hypersensitivity Pneumonitis, especially in US, most probably caused by mycobacterial antigens present in water-based oils. In Italy this disease is probably misdiagnosed or underreported. Some cross-sectional studies on respiratory disease and hearing loss, caused by the interaction of noise and chemical agent (mainly solvents), provided limited information because of the nature itself of this type of studies. Dermal pathologies still affect MWF exposed workers. Some antigens present in compounds, which are now gradually substituted, have been identified for allergic dermatitis (ADC). PMID- 22073668 TI - [Technological evolution in lubrorefrigeration and reduction of the potential effects on the health oe exposed individuals]. AB - Among the health risk for workers employed in metal working those related to cutting fluids were traditionally prominent. The main effects concerned respiratory and dermal pathologies from irritative-allergic (both chemical and biological) to mutagen and carcinogenic. These two latest effects have been demonstrated to increase with time of use. The attempt to reduce the chemical risks due to cutting fluid historically moved trough the constant decrease of mineral oil components by increasing their refinery. The innovative technological and preventive approach here presented consists on the contrary in changing the fluid basis with natural vegetal esters. The results confirmed similar or better technical characteristics of the fluids and a significant reduction of air pollution for example for polycyclic aromatic hydrocarbons (PAH) mixture, i.e. the most measured and studied toxic agents exposure to metal cutting fluid. PMID- 22073669 TI - [New welding processes and health effects of welding]. AB - This paper describes some of the recent developments in the control technology to enhance capability of Pulse Gas Metal Arc Welding. Friction Stir Welding (FSW) processing has been also considered. FSW is a new solid-state joining technique. Heat generated by friction at the rotating tool softens the material being welded. FSW can be considered a green and energy-efficient technique without deleterious fumes, gas, radiation, and noise. Application of new welding processes is limited and studies on health effects in exposed workers are lacking. Acute and chronic health effects of conventional welding have been described. Metal fume fever and cross-shift decline of lung function are the main acute respiratory effects. Skin and eyes may be affected by heat, electricity and UV radiations. Chronic effects on respiratory system include chronic bronchitis, a benign pneumoconiosis (siderosis), asthma, and a possible increase in the incidence of lung cancer. Pulmonary infections are increased in terms of severity, duration, and frequency among welders. PMID- 22073670 TI - [New varnishing techniques and health risk assessment]. AB - The first part of the report signals the significant changes coating processes have endured over the last twenty years. The shift from traditional "solvent based" paints to "water-based" paints marked a very important toxicological evolution, to reduce the possible toxic effects, to improve the products quality and to limit environmental pollution, Old and new recipes for preparation of paints and enamels are compared and discussed. The second part of the report summarizes the international literature concerning epidemiological data on painters and describes the toxic effects in experimental area that are reported for several solvents of water-based paints. PMID- 22073671 TI - ["Reach", "CLP" and "SDS": the impact on the chemical risk assessment]. AB - "REACH", "CLP" and "SDS" are Regulations that affect the rules on Health and Safety at Work and that, specifically, are linked to the chemical risk assessment. Up to 2015, the date when the old rules on Classification, Labeling and Packaging of hazardous substances and mixtures will be permanently abrogated, different regulations live together and for this reason is important to know every item in order to ensure the right training to the workers. In Italy, a Commission of the Ministry of Employment and Welfare has produced directions about the main consequences of the three Regulations on the D.Lgs. 81/2008. From an early analysis is essential to underline that the employer can make use of the Safety Data Sheet and the Labeling as basic tools to exchange information. PMID- 22073672 TI - [Risk assessment of chemical agents]. AB - The risk assessment of chemical agents is a well known and applied process carried out by Industrial Hygienists and Occupational Physicians based on exposure evaluation. The application of REACH (CE 1907/2006), CLP (CE 1272/2008) and SDS (UE 453/2010) introduces some changes and instruments to carry out the occupational exposure assessment, like new classification of substances, Exposure Scenario, suggested control measures that the Industrial Hygienist and the Occupational Physician must evaluate. If there is not a similar Exposure Scenario to apply a new risk assessment must carried out also by recommended software (ECETOC Targeted Risk Assessment; Easy to use workplace EMKG; Stoffenmanager). Looking at the relevance of the control measures and evaluation of Exposure Scenario we report the flowchart of risk assessment and management by the Method of Organisational Congruencies carried out with the Prevention and Protection Service and Occupational Physician Office of the Health Service of the Azienda Provinciale of Trento. PMID- 22073673 TI - [Bases and perspectives of biological monitoring: from the analysis of individual compounds in blood and urine to exposome characterization in exhaled air]. AB - PURPOSE: The present paper summarizes recent data concerning the use of exhaled breath condensate to characterize complex mixtures of both volatile (VOCs) and non-volatile substances giving rise to a human "exposome". RECENT FINDINGS: Data published over the last 10 years show that not only VOCs, but also toxic metallic elements are detectable in EBC, raising the possibility of using this medium to quantify the lung tissue dose of metals resulting from occupational exposures. Exhaled air is therefore a complement of the traditional approaches to biological monitoring aimed at assessing systemic doses. Different biomarkers of effect, such as biomarkers of oxidative stress and inflammation have also been applied in the investigation of occupational asthma and pneumoconiosis, suggesting that the collection of exhaled air and EBC may contribute to studying the pathological state of the airways of workers with acute and chronic exposure to pneumotoxic pollutants. The same noninvasive approach may open new frontiers in the study of workers currently or previously exposed to pulmonary carcinogenic agents characterizing their respiratory "exposome", as well as their lung pathobiology or "breathomics". SUMMARY: Currently, research on biomonitoring is focusing on the characterization of complex patterns of exposures relying on noninvasive methods, particularly suitable to be applied infield studies and for longitudinal assessments of pulmonary biology frequently affected in occupational settings. PMID- 22073674 TI - [International applications and experiences in biological monitoring: state of the art]. AB - Biological monitoring (BM) represents one of the most dynamic areas of research in occupational health today. From a few tens of articles published yearly in the 70s and 80s, there are now several thousand papers published in the peer review literature each year and the trend is still growing. BM was originally used to assess exposure, effects and susceptibility to occupational agents, but it has been now extended to environmental chemical risk assessment, as well as to several other biomedical sciences, such as epidemiology, tumor science, molecular biology, to mention just a few. The aim of the present paper is to consider new experiences in the use of BM at the international level and to discuss the contribution that these approaches may provide to develop new diagnostic and preventive tools in occupational and environmental health. PMID- 22073675 TI - [Chemical risks. From the risk assessment to the sanitary surveillance: evolution of the instruments of the occupational health]. AB - Following the development of Legislation, the Occupational Health activities become more articulated and complex from both a formal and essential point of view and they are becoming an ever increasing part of the Health and Safety preventative strategy at the workplace and in its surrounding environment. In this context Health Surveillance, including its risk assessment aspect, is not any more only the straightforward application of medical methods aimed at identifying work related pathologies, but it assumes a preventative role in the evaluation of the individual exposure to the work environment i.e. to chemical and biological substances. To carry out such activities, in addition to the ones normally used, new instruments of information are available, provided by recent legislation, that regulates in a coordinated way the worker's health protection at the workplace, in particular the Regulation n. 1907/2006 (REACH) and the Regulation n.1272/2008 (CLP). PMID- 22073676 TI - [Algorithms for the evaluation of chemical risk: the Piedmont Region's experience]. AB - The programme InfoRisk, proposed by the Piedmont Region in 2002, has been an important reference point for the evaluation of chemical risk, both for companies and the regional prevention system alike. Nowadays, it is still considered necessary to take advantage of simple methods for the evaluation of this risk. However, the Piedmontese model requires some modification so as to keep it in line with the national and international rules and regulations governing the question and to find some solutions to problems that have arisen in its practical application. Most of these problems are tied to the use of the section of the evaluation technique, which is base on the estimate and not on the measurement of the exposure. Indeed, it has been confirmed in some cases that it is not possible to discard a more accurate evaluation which is not only able to make a correct application of the scientific evidence available in a correct manner, but also one that is supported by environmental monitoring campaigns. The main modifications proposed to the model are herein presented. The Work Group has endeavoured to maintain, whenever possible, the previous logic processes of the algorithm, so as to conserve its "user friendly" aspects and clarity that have so often been reported and appreciated by the operators who applied it. PMID- 22073677 TI - Occupational cancer epidemiology. AB - Occupational cancer epidemiology has led to the identification of more than 40 agents, groups of agents, and exposure circumstances which cause cancer in humans. This evidence has been followed by preventive and control measures. There are four areas where occupational cancer epidemiology may contribute important results in the future: surveillance of workers exposed to carcinogens, identification of new carcinogens and target organs, study of interactions, and research on special exposure circumstances. PMID- 22073678 TI - [Mechanistic issues and prevention strategies targeting occupational carcinogenesis]. AB - Carcinogenesis can be visualized either as a multistep process (initiation, promotion, progression, invasion, and metastasis) or as a continuum of mutagenic and mitogenic events, with the contribution of epigenetic mechanisms. The exponential growth of the neoplastic mass explains the importance of secondary prevention (early diagnosis) and of tertiary prevention. Primary prevention, which was successful in controlling occupational cancers, aims at minimizing exposures to carcinogens in healthy subjects and at favoring the intake of chemopreventive agents with dietary and pharmacological agents. Besides chemical carcinogens, often in the form of complex mixtures, the workplace may involve exposures to physical agents, such as sunlight and artificial illumination systems delivering UV radiation, or to biological agents, such as chronic viral infections (HBV, HCV, and HIV) associated with cancers. A controversial issue is the occurrence of threshold doses for carcinogens in the workplace and the environment. PMID- 22073679 TI - [A new update of the SIMLII Guidelines on carcinogens]. AB - The second update of the Italian Society of Occupational Medicine and Industrial Hygiene (SIMLII) guidelines on Cancerogens and Mutagens, first published in 2003 and reviewed in 2007, is presented. The general setting of the guidelines remaines unmodified. In this new release some important developments on regulatory system, risk assessment, and health surveillance are discussed. The relevant evolution of the regulatory rules is illustrated in detail, with particular reference to the recent implementation in European Union and in Italy of the Regulation (EC) 1272/2008 on Classification, Labelling and Packaging of substances and mixtures. The recent tendencies of the European Scientific Committee on Occupational Exposure Limits in risk assessment, are presented. Some remarks on the use of new biomarkers in health surveillance, with reference to lung and bladder cancer, are discussed. The more recent results on the effectiveness of the use of LDTC scan on screening in asymptomatic persons at high risk for lung cancer, are presented. The use of this imaging technique in health surveillance of special group of workers (i.e., subjects with relevant past asbestos exposure and smokers) could be adopted. PMID- 22073680 TI - [Causality in occupational oncology: the toxicologist opinion]. AB - General and individual causality in occupational oncology should be regarded as diverse and largely autonomous concepts. General causality is based upon a statement such as "the chemical is a carcinogen" and must be considered for preventive action. Individual causality implies that the statement has to be applied to a patient exposed to that chemical. Whereas cancer results from complex interactions between genes and, in broad sense, the environment, the individual causality is an empirical judgement (educated guess) based upon all information about the substance itself and the individual patient. PMID- 22073681 TI - A framework for causal inference in occupational epidemiology. AB - The observational nature of occupational epidemiology research is a reason for potentially divergent interpretation of the causal nature of the results of studies addressing the association between an exposure and a disease. There is a need for frameworks that explicitly define the steps involved in this process of deriving causal inference from occupational epidemiology. A recent proposal consisted of the following steps: (i) study identification, (ii) quality assessment and categorization, (iii) evaluation of the weight of the evidence, and (iv) assignment of a scalable conclusion. While other approaches can be proposed, efforts to improve the quality and transparency of the process are helpful and represent a contribution to this essential component of occupational epidemiology research. PMID- 22073682 TI - [Causation in the court: the complex case of malignant mesothelioma]. AB - The aim of this paper is to carry out an analysis of the legal evolution in Italy of the assessment of causation i.e. cause and effect, in oncological diseases, a question taken into consideration by the High Court almost exclusively with reference to pleural mesothelioma. The most debated question when defining the causal association between asbestos exposure and mesothelioma is the possible role that any multiple potentially causative exposures could assume in the induction and development of the disease, and in particular the role of any asbestos exposure over the successive employment periods. Indeed, this is a subject on which, to date, no agreement has yet been reached in scientific doctrine: these divergences bear important practical significance from a legal point of view, since sustaining one thesis or another may constitute determining factors when ascertaining responsibility for individuals who, in the past, had decisional statuses in the workplace. Jurisprudence in the High Court took on an oscillating position on this question as from the early 2000s, which was divided into those who sustained the thesis of the relevance of any asbestos exposure over the successive employment periods and those who were of a different opinion, i.e. only the first exposure period has relevant causative effect. The point under discussion concerns, in particular, the adequacy of a probabilistic law only governing such a question. An important turning point was made in the year 2010 when two sentences were announced in the High Court, reiterating, in strict compliance with the principles affirmed by the United Sections in 2002, that a judge cannot, and must not, be satisfied with a general causation, but must rather reach a judgment on the basis of an individual causation. In particular, not only did the second of these two sentences recognise the multifactorial nature of mesothelioma, something which had almost always been denied in jurisprudence in the past, but it also established some very clear legal principles of law. Essentially, when ascertaining the causation, a judge should verify whether or not there is a sufficiently well established scientific law covering the question and whether such a law is universal or probabilistic. Should the latter be the case, then it is necessary to establish if the accelerating effect has been determined in the case in question, on the basis of the factual acquisitions. We must now wait for the concrete application of these principles by juridical bodies. PMID- 22073683 TI - [NHIL epidemiology in Italy. 20 years from DLgs 277/91: review and expectations]. AB - Digs 277/91 and following related laws brought up a large number of NHILs, but also planned surveillance more and more effective in preventing hearing loss. In these two decades we also saw an inversion in percentages between working populations. The Authors analize these two factors, better and wider prevention and changing in work populations, related to resulting reduction of NHIL's cases. Besides, the Authors compare different insurance scales adopted to evaluate hearing damage in this period, bringing out similarities. INAIL's path achieved another last goal since 2007 in planning the new protocol about hearing aids, aiming to more effective compensation of the recognized hearing loss, looking more at "Biological value" of the person than at former "working capability". PMID- 22073684 TI - [The technical prevention of chronic acoustic trauma]. AB - The present legislation establishes that workers' exposure to noise, which is the cause of chronic acoustic trauma, should be limited through the adoption of measures of technical and organizational nature. Organizational actions involve a plurality of aspects, not only technical in character, which are usually more difficult to apply and less rewarding in terms of acoustic benefits as compared to the technical ones; the latter should be primarily applied to the source, but are often adopted also at the noise propagation or reception level. Following a short summary of the normative framework, the article describes the approach that may be adopted in order to establish, in a given industrial setting, the priorities of intervention aimed at minimizing the noise exposure risk for the highest number of exposed workers. PMID- 22073685 TI - [The prevention of noise inducted hearing loss: the new challenge of active electronic hearing protection]. AB - Based on today's common hearing aid design and technology, the team of researchers successfully designed a DPI which allows the worker to be "protected" against loudness and in the same time guarantee a good level of communication and perception of the surrounding environment. The design of this new device is very much similar to a standard BTE hearing aid which allows the use of an active DPI very comfortable, robust and easy to use. The research using the prototypes was divided into 3 phases: Phase 1: 24 volunteers coming from non-industry companies did undergo a specific trial protocol. Phase 2: 6 workers coming from a mining company did undergo the same protocol used in Phase 1. Phase 3: The Acoustics Laboratory from the "Energetica" Department of the Polytechnic of Turin (University/Institute) took objective measures for the DPI attenuation figures used in phase 1 and 2. PMID- 22073686 TI - [Hearing loss and idoneity--the segnalation of noise-induced hearing loss hearing Loss]. AB - Work idoneity in hearing loss must be related to working ability and evolution risks. Working ability is referred to the difficulties found in speech comprehension and in signals perception. As regards hearing loss evolution it is necessary to define if the subject is affected by conductive or neurosensorial hearing loss. In conductive hearing loss it is necessary to evaluate entity and frequential distribution of the deficit. In neurosensorial hearing loss it is necessary to distinguish between noise-induced hearing loss and extraprofessional hearing loss. In noise-induced hearing loss the evolution risk is high if the noise exposure is less than 10-15 years or the actual noise exposure is louder than the former. In case of extraprofessional hearing loss the evolution risk is higher in presbycusis, endolymphatic hydrops and toxic hearing loss. The necessity to report the presence on professionale noise-induced hearing loss arises if audiometric threshold is more than 25 dB at 0.5-1-2-3-4 kHz and if it is verified the professional origine of hearing loss. PMID- 22073687 TI - [Issues concerning the measurement and assessment of noise in workplaces]. AB - The measurement and assessment of noise in workplaces are affected by several critical aspects. Only the equivalent sound pressure levels are measured and all the other acoustical parameters are almost always neglected; the non-acoustic information that characterize each measurement are not usually reported. The survey about noise in workplaces is not suited to be described by technical standards, but rather by flexible guidelines. The reference standard UNI EN ISO 9612/2011 does not highlight the contribution given by each work phase to the overall exposure level; the uncertainty evaluation may lead to unreliable data. PMID- 22073689 TI - [Socio-presbyacusis: definition and prevention]. AB - Socio-presbyacusis is a hot topic with an increasing incidence and high social costs. The main etiological factors are: genetics, smoking and drinking habits, diet, metabolic syndrome, chronic otitis and noise exposure (professional, environmental and recreative). Despite its multifactorial origin, the pathogenetic mechanism of cochlear damage is based on the increased production of Reactive Oxygen Species (ROS). The clinical characteristic feature of socio presbyacusis is represented by slow cochlear degeneration causing a reduction of central hearing inputs. The result is a gradual social isolation of the deaf patient with a worsening of his Quality of Life. The main target of the management of socio-presbyacusis is the early diagnosis and prosthetic remediation in order to avoid patient's isolation. New preventive and remediative strategies are represented by antioxidant drugs. PMID- 22073688 TI - [Non-auditory effects of noise]. AB - Non-auditory effects of noise involve several systems and functions, the most important of which are the cardiovascular, the vestibular and the psychic. Although several studies correlated noise exposure to some pathologies, like hypertension and anxiety disorders, and recent analysis carried out on cavy explained part of their pathophysiology, their multiple causes and the variability of individual reactions are still important limits to their classification. PMID- 22073690 TI - [Emigration and immigration in Italy. (1861-2011)]. AB - The creation of the Italian Kingdom was characterized by the mass emigration of Italian people, mainly peasants towards European and American destinations. Poverty, unemployment, diseases, like pellagra, malaria and tubercolosis forced millions of Italians to leave the Country. The phenomenon of emigration is usually divided in three periods: the mass emigration from 1976 to 1914, the second one between the two world wars, the third one from 1946 to 1976. In the last quarter of the 20th century the number of repatriations overcome expatriations and the number of immigrants from Albania, Romania, Senegal, Tunisia, China, Philippines grew up becoming more and more important. Italy was a country of emigrants, now is a country of immigrants. It is difficult to compare the work conditions of the Italian emigrants with the new immigrants. At the end of the 19th Century or in the first decades of the 20th Century there were no consideration for human rights, no legislations to protect workers. Immigration from North Africa and from all the low and middle income countries should be studied in all its aspects because it will characterize our future. In the new era of economical globalization, Universities should prepare the new medical doctors to extend their professional culture to a international dimension to be able to cope with the new challenges of our time. PMID- 22073691 TI - [The management of foreign workers in Italy]. AB - Over the last decades, the globalisation and important geopolitical changes have widened the spatial boundaries of international migrations which have reached a so global scope today that they influence the economic, political and social trend of countries of origin, transit and destination. According to the UN, the international labour mobility involved more than 200 million people in 2010, that is approximately 10% of the world's total population. In Italy, in the beginning of 2010 foreign residents amounted to 4.2 million, that is to say, 7% of the total population (ISTAT, 2011). Host countries have been forced to implement a series of policies aimed at combating illegal immigration and employment of foreign people. Special attention must be given to the issue of migrant workers who have become increasingly important actors in the social and productive sectors and, as a consequence, the need for preventive and protective measures taking into consideration the specific work-related hazards is growing more and more urgent. With this respect, the regulatory framework for occupational health and safety now contains explicit references to migrant workers as provided in the Leg. Decree 81/08 with subsequent integrations and modifications. First of all, the issue of occupational health and safety for migrant workers must take into account of the linguistic, social and cultural problems of the different ethnical groups that are present in our country. PMID- 22073692 TI - [Health management of Italian workers abroad]. AB - In the last 20 years traveling workers abroad have increased markedly. This resulted in the need for standardized preventive tools available to protect workers-travelers in geographic areas with related additional risk factors. Health surveillance of these workers require a company organization that involves the components of the process prior: the occupational physician, safety service, administrative areas, travel clinic. The application phases of medical surveillance must be differentiated into two main phases: 1. pre-travel, in which successive stages also encoded by the SIMLII guidelines; 2. the return journey, where the paths are different for asymptomatic and symptomatic workers. The evaluation of fitness to perform the job abroad is based on general criteria that allow to correlate the health of the worker with respect to the destination area. The application methods actually available allow modulations of the health surveillance for companies of different dimension. PMID- 22073694 TI - [Migrant workers. The critical aspects of integration]. AB - The integration of migrant poplulations with the indigeneous population is regulated by the Italian Decree, D.Lgs 9/7/2003 n. 215 in enforcement of the directive 2000/43/EC implementing the principle of equal treatment between persons irrespective of racial or ethnic origin. The Italian decree, D.Lgs 215/2003, at present in force, according to regulation stipulated as to the equal treatment of diverse cohabiting populations, explicitly forbids any form of discrimination whatsoever, be it direct or indirect. A first description of today's migrant panorama is offered by the Caritas Migrantes and the CNEL (Italian National Council of the Economy of Labour). The most critical aspects on the integration of migrants are described and discussed in the text. PMID- 22073693 TI - ILO - International Migration Programme. AB - In a wide International Context characterised not only by the economical development but also by the social, cultural, political and individual development, we witness more and more to a exchange between the developed and the developing countries, which can be translated especially in the migration of the work force. In theory, all countries are either countries of origin either countries of transit or destination, and they are all responsible for the rights of migrant workers by promoting the rights, by monitoring and by preventing the abusive conditions. The process of migration of the workforce can be divided into three stages: the first coincides with the period prior to departure, the second is represented by the aftermath of the departure and the period of stay in the country of destination, the third stage corresponds to the return in the country of origin. The workers must be protected throughout this process by the international organizations that perform the catalytic role of communication and exchange between countries, for the only purpose of protecting the rights of immigrant and/or immigrants workers. The responsibility for the protection of workers is divided among the various players in the International Labour Organisation. Every country has to apply measures according to the international standards regarding workers' rights, standards that guide the various countries in the formulation and implementation of their policies and legislation. These standards are suggested by International Conventions, the ILO Conventions and other international instruments such as the human rights instrument. There has been a big step forward once the ILO Fundamental Conventions and Conventions on Migrant Workers where implemented and this implementation represented the use of the Guidelines "ILO Multilateral Framework on Labour Migration". PMID- 22073695 TI - [Transfer and continuity of care: we need to talk about both]. PMID- 22073696 TI - [Monitoring of heparins and of anticoagulants]. AB - Anticoagulation with unfractionated heparin, low molecular weight heparin or fondaparinux is common practice in thromboembolic disease, atrial fibrillation and mechanical heart valves. Some of these molecules, with specific pharmacokinetic, requires specific monitoring. Unfractionated heparin requires close monitoring by aPTT and/or anti-FXa activity while LMWH and fondaparinux do not require biological surveillance except in a few specific situations. PMID- 22073697 TI - [Iron-deficient anemia, anemia of chronic disease or mixed anemia: how to determine the diagnosis?]. AB - The diagnosis of pure iron-deficient anemia or anemia of chronic disease is easy. However, in mixed situations, conventional laboratory tests for iron status are influenced by the inflammatory response and their diagnostic accuracy may be undermined. New tests are available but grey zones and diagnostic uncertainties sometimes remain. The objective of this article is to give an overview of the current diagnostic tools for the evaluation of the iron metabolism and to provide a practical diagnostic algorithm for the evaluation of iron-deficient anemia. PMID- 22073698 TI - [Usefulness of medical history and physical findings in the diagnosis of pneumonia]. AB - Pneumonia is a frequent concern in the ambulatory setting. Diagnosis should be prompt, as delays in the instauration of the treatment are associated with a worse prognosis. However, empiric antibiotic treatment of all patients suspected of having pneumonia is unwarranted, and can affect adversely bacterial ecology. Chest X-ray remains the gold standard, and should always be obtained to confirm the diagnosis, as clinical findings are non-specific. Conversely, some clinical findings can be used to rule out pneumonia with sufficient negative predictive value in a low-prevalence setting. A chest X-ray can be omitted for these patients. We aimed to point which symptoms and signs are useful in assessing the clinical probability of pneumonia, and review clinical rules proposed for this purpose. PMID- 22073699 TI - [Management of acute alcoholic steatohepatitis]. AB - Alcoholic steatohepatitis is an acute inflammatory liver disorder that often complicates the course of underlying cirrhosis. Severe alcoholic steatohepatitis, defined as a Maddrey's discriminant function greater than 32 or association with hepatic encephalopathy, carries a high short-term mortality that is significantly reduced by corticosteroids. A comprehensive work-up is necessary for the presence of concomitant infection or associated viral hepatitis. A liver biopsy must be performed to confirm the diagnosis prior to initiation of steroids. This article summarizes the management of alcoholic steatohepatitis. PMID- 22073700 TI - [Beta-blocker therapy during acutely decompensated heart failure]. AB - The well established benefits of beta-blocker therapy in chronic heart failure include improved survival and quality of life and decreased morbidity and hospitalizations. In acute heart failure, evidence supports early initiation of beta-blocker therapy within the same hospitalization. Beta-blocker therapy seldom has to be withdrawn if patients are already on this medication as maintaining beta-blockers throughout these episodes is not deleterious and increases ulterior therapeutic adhesion. Possible indications for temporarily discontinuing therapy are a worsening clinical condition or cardiogenic shock. Potential benefits of maintaining beta-blockers on mortality still have to be confirmed by larger prospective trials. PMID- 22073701 TI - [Use of glucocorticoids in low back pain due to disc herniation with radicular involvement]. AB - Although systemic glucocorticoids are frequently used for the treatment of radicular pain due to disc herniation, there are only few studies available. No trial has successfully demonstrated the superiority of systemic glucocorticoids compared to placebo. Therefore their use is not recommended. Spinal injection using radiographic guidance appears to provide some beneficial short-term effect on pain. It might be offered when pain treatments according to the WHO steps have failed. Because rare but serious adverse events have been reported, transforaminal periradicular injections should only be used after thorough analysis of risks and benefits with the patient. PMID- 22073702 TI - [Zinc for a cold?]. PMID- 22073703 TI - [Release prescribers from their prescriptions?]. PMID- 22073704 TI - [Lapsus]. PMID- 22073705 TI - [Giving birth anonymously versus the "towers of abandonment" (2)]. PMID- 22073706 TI - [Georges Courteline on the menus of canteens of France]. PMID- 22073707 TI - [I know I have cancer]. PMID- 22073708 TI - Suspected bile duct injuries and appropriate early referral can reduce chances of litigation. AB - Bile duct injury following laparoscopic cholecystectomy is one of the most feared complications related to performing a cholecystectomy. Early identification and repair can be life saving for patients with bile duct injuries. Since the early 1990s, laparoscopic cholecystecomy (LC) has replaced open cholecystectomy as the preferred treatment of symptomatic cholethiasis, biliary dyskinesia, and cholecystitis. LC has decreased the length of hospital stay and post-operative pain and resulted in a subsequent faster return to normal daily activities; nonetheless, LC has a higher incidence in bile duct injury as compared to open cholecystectomy. Nearly all studies report the incidence of bile duct injury following open cholecystectomy between 0.1% and 0.2%. In comparison, LC has a reported incidence of bile duct injury between 0.4% and 0.7%. The aim of this article is to review our initial experience with work-up and repair of bile duct injuries following LC performed at outside facilities and referred to the University of Mississippi Medical Center (UMMC) for definitive therapy. We will also review the classification of these injuries, preferred methods of diagnosis, and benefits of early treatment as well as factors that frequently lead to litigation following bile duct injury. PMID- 22073709 TI - Use of non-invasive ventilation in general ward for the treatment of respiratory failure. AB - Non-invasive ventilation (NIV), the provision of ventilatory assistance without an artificial airway, has emerged as an important ventilatory modality over the last 20 years. Delivery of pressured air at a certain level through a nasal or oro-nasal mask improves oxygenation and reduces ventilatory muscle fatigue. The equipment consists of a ventilator (typically a CPAP or BiPAP machine) with tubing, headgear, nasal or facial mask, filter and humidifier (Figure 1). In this article, we will discuss the medical literatures that support the use of NIV safely and effectively on the general medical floor to treat respiratory failure secondary to acute exacerbation of chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF). PMID- 22073710 TI - Inaugural address of the president. 143rd annual session, 2011-12. Chewing the fat on cutting fat. PMID- 22073711 TI - Remembering Peru: what those who made the journey had to say. AB - Each year, the University of Mississippi Medical Center (UMMC) Department of Infectious Diseases teams up with Project Amazonas (www.projectamazonas.org), a humanitarian aid organization whose home base is Peru. Together healthcare workers and humanists travel by boat to the wilds of Peruvian Amazon to bring aid and education to a beautifully hidden and underserved world of Amazonian River people. PMID- 22073712 TI - When time is muscle: an update on Mississippi's STEMI system of care plan. PMID- 22073713 TI - Grits report 2011: Much accomplished by Mississippi at AMA (despite smaller number of delegates). PMID- 22073714 TI - The value of oral health. PMID- 22073715 TI - Compliance with new 401(k) disclosure requirements. PMID- 22073716 TI - Membership: a top priority for the ADA. PMID- 22073718 TI - When in doubt, predetermine. PMID- 22073717 TI - Mean girls! What happens when they grow up and come to work for you. PMID- 22073720 TI - Comparing MDA peer review with the state's disciplinary process. PMID- 22073719 TI - Tips for caring for an aging parent: part two. PMID- 22073721 TI - Options for provisionalization following dental implant placement in partially edentulous sites. PMID- 22073722 TI - Oral manifestations of celiac disease: a clinical guide for dentists. AB - Celiac disease (gluten sensitive enteropathy) is a common disorder affecting both children and adults. As many people with celiac disease do not present with the classic malabsorptive syndrome, delays in diagnosis are common. Dental enamel defects and recurrent aphthous ulcers, which may occur in patients with celiac disease, may be the only manifestation of this disorder. When dentists encounter these features, they should enquire about other clinical symptoms, associated disorders and family history of celiac disease. In suspected cases, the patient or family physician should be advised to obtain serologic screening for celiac disease and, if positive, confirmation of the diagnosis by intestinal biopsy. Dentists can play on important role in identifying people who may have unrecognized celiac disease. Appropriate referral and a timely diagnosis can help prevent serious complications of this disorder. PMID- 22073723 TI - Go team! The benefits of a morning huddle. PMID- 22073724 TI - The effect of digestion and dewatering on sudden increases and regrowth of indicator bacteria after dewatering. AB - Several investigators have reported higher densities of indicator bacteria after dewatering of anaerobically digested biosolids. The increases appear to occur at two points in the biosolids process: the first, referred to as "sudden increase", occurs immediately after dewatering; the second, "regrowth", occurs during storage over longer periods. The objectives of this study were to examine the effect of digestion and dewatering processes on sudden increase and regrowth of fecal coliform and E. coli. Samples were collected from five thermophilic and five mesophilic digestion processes, with either centrifuge or belt filter press dewatering. Sudden increase typically was observed in the thermophilic processes with centrifuge dewatering and was not observed in the mesophilic processes with either centrifuge or belt filter press dewatering. Regrowth was observed in both thermophilic and mesophilic processes with centrifuge dewatering but not belt filter press dewatering. PMID- 22073725 TI - Adsorption of glyphosate on resin supported by hydrated iron oxide: equilibrium and kinetic studies. AB - Hydrated iron oxide supported on resin (D301) was prepared as a new sorbent for the removal of glyphosate from wastewater. Batch adsorption studies were performed on glyphosate aqueous solutions with different initial glyphosate concentrations and temperatures. Experimental data were analyzed using the Langmuir and Freundlich isotherms, and the adsorption data were best fit to the Langmuir isotherm model. The thermodynamic parameters AG, AH, and AS also were calculated for the adsorption processes. Adsorption rate constants were determined using the pseudo-first-order and pseudo-second-order rate equations and Kannan-Sundaram intraparticle diffusion models. Adsorption of glyphosate clearly followed the pseudo-second-order model and was controlled by both film diffusion and intraparticle diffusion. PMID- 22073726 TI - A mathematical model for the interactive behavior of sulfate-reducing bacteria and methanogens during anaerobic digestion. AB - Anaerobic degradation of waste involves different classes of microorganisms, and there are different types of interactions among them for substrates, terminal electron acceptors, and so on. A mathematical model is developed based on the mass balance of different substrates, products, and microbes present in the system to study the interaction between methanogens and sulfate-reducing bacteria (SRB). The performance of major microbial consortia present in the system, such as propionate-utilizing acetogens, butyrate-utilizing acetogens, acetoclastic methanogens, hydrogen-utilizing methanogens, and SRB were considered and analyzed in the model. Different substrates consumed and products formed during the process also were considered in the model. The experimental observations and model predictions showed very good prediction capabilities of the model. Model prediction was validated statistically. It was observed that the model-predicted values matched the experimental data very closely, with an average error of 3.9%. PMID- 22073727 TI - Combined anaerobic/aerobic digestion: effect of aerobic retention time on nitrogen and solids removal. AB - A combined anaerobic/aerobic sludge digestion system was studied to determine the effect of aerobic solids retention time (SRT) on its solids and nitrogen removal efficiencies. After the anaerobic digester reached steady state, effluent from the anaerobic digester was fed to aerobic digesters that were operated at 2- to 5 day SRTs. The anaerobic system was fed with a mixture of primary and secondary sludge from a local municipal wastewater treatment plant. Both systems were fed once per a day. The aerobic reactor was continuously aerated with ambient air, maintaining dissolved oxygen level at 1.1 +/- 0.3 mg/L. At a 4-day or longer SRT, more than 11% additional volatile solids and 90% or greater ammonia were removed in the aerobic digester, while 32.8 mg-N/L or more nitrite/nitrate also was measured. Most total Kjeldahl nitrogen removal was via ammonia removal, while little organic nitrogen was removed in the aerobic digester. PMID- 22073728 TI - Corrosion control when using passively treated abandoned mine drainage as alternative makeup water for cooling systems. AB - Passively treated abandoned mine drainage (AMD) is a promising alternative to fresh water as power plant cooling water system makeup water in mining regions where such water is abundant. Passive treatment and reuse of AMD can avoid the contamination of surface water caused by discharge of abandoned mine water, which typically is acidic and contains high concentrations of metals, especially iron. The purpose of this study was to evaluate the feasibility of reusing passively treated AMD in cooling systems with respect to corrosion control through laboratory experiments and pilot-scale field testing. The results showed that, with the addition of the inhibitor mixture orthophosphate and tolyltriazole, mild steel and copper corrosion rates were reduced to acceptable levels (< 0.127 mm/y and < 0.0076 mm/y, respectively). Aluminum had pitting corrosion problems in every condition tested, while cupronickel showed that, even in the absence of any inhibitor and in the presence of the biocide monochloramine, its corrosion rate was still very low (0.018 mm/y). PMID- 22073729 TI - Anaerobic digestion of raw and thermally hydrolyzed wastewater solids under various operational conditions. AB - In this study, high-solids anaerobic digestion of thermally pretreated wastewater solids (THD) was compared with conventional mesophilic anaerobic digestion (MAD). Operational conditions, such as pretreatment temperature (150 to 170 degrees C), solids retention time (15 to 20 days), and digestion temperature (37 to 42 degrees C), were varied for the seven THD systems operated. Volatile solids reduction (VSR) by THD ranged from 56 to 62%, compared with approximately 50% for MAD. Higher VSR contributed to 24 to 59% increased biogas production (m3/kg VSR d) from THD relative to MAD. The high-solids conditions of the THD feed resulted in high total ammonia-nitrogen (proportional to solids loading) and total alkalinity concentrations in excess of 14 g/L as calcium carbonate (CaCO3). Increased pH in THD reactors caused 5 to 8 times more un-ionized ammonia to be present than in MAD, and this likely led to inhibition of aceticlastic methanogens, resulting in accumulation of residual volatile fatty acids between 2 and 6 g/L as acetic acid. The THD produced biosolids cake that possessed low organic sulfur-based biosolids odor and dewatered to between 33 and 39% total solids. Dual conditioning with cationic polymer and ferric chloride was shown to be an effective strategy for mitigating dissolved organic nitrogen and UV quenching compounds in the return stream following centrifugal dewatering of THD biosolids. PMID- 22073730 TI - Oxidized starch solutions for environmentally friendly aircraft deicers. AB - Deicers currently used for aircraft deicing, including ethylene glycol and propylene glycol, pose significant threats to surface waters, as a result of high biochemical oxygen demand (BOD) and toxicity to aquatic organisms. Oxidized starch may provide a less toxic deicer with lower BOD. The freezing point depression of starch formulations oxidized using hydrogen peroxide and catalysts (i.e., catalyzed hydrogen peroxide [H2O2] propagations-CHP) was 28 degrees C, and viscosities similar to those of commercial deicers were achieved after post treatment with granular activated carbon. The most effective oxidized starch formulation exerted a 5-day BOD up to 6 times lower than glycol deicers (103 versus 400 to 800 g O2/L). Toxicity to Ceriodaphnia dubia for this formulation (48-hour lethal concentration, 50% [LC50] of 2.73 g/L) was greater than pure propylene glycol (13.1 g/ L), but lower than propylene glycol deicer formulations (1.02 g/L). Organic acids were identified by gas chromatography/mass spectrometry as the primary constituents in the oxidized starch solution. The proposed deicing system would provide effective deicing while exerting minimal environmental effects (e.g., lower toxicity to aquatic organisms and lower BOD). Furthermore, these deicers could be made from waste starch, promoting sustainability. PMID- 22073731 TI - Removal of mercury(II) from aqueous solutions using the leaves of the Rambai tree (Baccaurea motleyana). AB - This study was undertaken to evaluate the biosorption potential of a natural, low cost biosorbent, Rambai leaves (Baccaurea motleyana), to remove trace amounts of Hg(II) from aqueous solutions. It was found that the amount of Hg(II) biosorption by Rambai leaves increased with initial metal ion concentration, contact time, and solution pH but decreased as the amount of biosorbent increased. The maximum biosorption capacity was 121.95 mg/g for an initial concentration range of 5 to 120 ppb. Overall, kinetic studies showed that the Hg(II) biosorption process followed pseudo-second-order kinetics based on pseudo-first-order and intraparticle diffusion models. Isotherm data revealed that the biosorption process followed both Freundlich and Langmuir isotherms. The value of separation factor, R(L), from the Langmuir equation and rate of biosorption, n, from the Freundlich model also indicated favorable adsorption. PMID- 22073732 TI - Laboratory and field evaluation of a pretreatment system for removing organics from produced water. AB - Co-produced water from the oil and gas industry accounts for a significant waste stream in the United States. This "produced water" is characterized by saline water containing a variety of pollutants, including water soluble and immiscible organics and many inorganic species. To reuse produced water, removal of both the inorganic dissolved solids and organic compounds is necessary. In this research, the effectiveness of a pretreatment system consisting of surfactant modified zeolite (SMZ) adsorption followed by a membrane bioreactor (MBR) was evaluated for simultaneous removal of carboxylates and hazardous substances, such as benzene, toluene, ethylbenzene, and xylenes (BTEX) from saline-produced water. A laboratory-scale MBR, operated at a 9.6-hour hydraulic residence time, degraded 92% of the carboxylates present in synthetic produced water. When BTEX was introduced simultaneously to the MBR system with the carboxylates, the system achieved 80 to 95% removal of BTEX via biodegradation. These results suggest that simultaneous biodegradation of both BTEX and carboxylate constituents found in produced water is possible. A field test conducted at a produced water disposal facility in Farmington, New Mexico confirmed the laboratory-scale results for the MBR and demonstrated enhanced removal of BTEX using a treatment train consisting of SMZ columns followed by the MBR. While most of the BTEX constituents of the produced water adsorbed onto the SMZ adsorption system, approximately 95% of the BTEX that penetrated the SMZ and entered the MBR was biodegraded in the MBR. Removal rates of acetate (influent concentrations of 120 to 170 mg/L) ranged from 91 to 100%, and total organic carbon (influent concentrations as high as 580 mg/L) ranged from 74 to 92%, respectively. Organic removal in the MBR was accomplished at a low biomass concentration of 1 g/L throughout the field trial. While the transmembrane pressure during the laboratory-scale tests was well controlled, it rose substantially during the field test, where no pH control was implemented. The results suggest that pretreatment with an SMZ/MBR system can provide substantial removal of organic compounds present in produced water, a necessary first step for many water-reuse applications. PMID- 22073733 TI - Full-scale use of glycogen-accumulating organisms for excess biological carbon removal. AB - The purpose of this study has been to verify the efficient full-scale applicability of glycogen-accumulating organisms (GAOs) for excess biological carbon removal, that is, for removing more carbon substrate than the amount of available nutrients would allow in the conventional activated sludge process of microbial growth. This aims to cost-effectively overcome the problem of viscous bulking occurring in a fully aerated system, with nutrient deficiency. Analytical data measured at the wastewater treatment plant of the Balatonboglar (BB) winery in Balatonboglar, Hungary, containing consecutive unaerated and aerated activated sludge basins, reflected a high performance with efficient carbon removal and good sludge settling, without dosing any external nutrient source to the severely nitrogen- and phosphorous-deficient influent. Supplementary laboratory-scale batch experiments and microbiological tests verified the abundance of GAOs in the activated sludge system and elucidated their role in efficient excess biological carbon removal. PMID- 22073734 TI - Complete dechlorination of endosulfan and lindane using Mg0/Pd(+4) bimetallic system. AB - A Mg0/Pd(+4) bimetallic system was evaluated to dechlorinate endosulfan and lindane in the aqueous phase. Studies were conducted with endosulfan and lindane separately, with or without acid in a 1:1 (v/v) water:acetone phase. In the absence of any acid, higher degradation of endosulfan and lindane was observed using Mg0/Pd(+4) doses of 10/0.5 and 4/0.1 mg/mL, respectively. Acetone plays an important role in facilitating the dechlorination reaction by increasing the solubilities of pesticides. Dechlorination kinetics for endosulfan and lindane (30 and 50 mg/L [30 and 50 ppm] concentration of each pesticide) were conducted with varying Mg0/Pd(+4) doses, and the time-course profiles were well-fitted into exponential curves. The optimum observed rate constants (k(obs)) for endosulfan and lindane were obtained with Mg0/Pd(+4) doses of 5/0.5 and 4/0.1 mg/mL, respectively. Gas chromatography-mass spectrometry analyses revealed that endosulfan and lindane were dechlorinated completely into their hydrocarbon skeletons-Bicyclo [2,2,1] hepta 2-5 diene and benzene, respectively. PMID- 22073735 TI - Biomass-derived materials in the remediation of heavy-metal contaminated water: removal of Cadmium(II) and copper(II) from aqueous solutions. AB - Manganese-coated activated carbon (MCAC) and activated carbon were used in batch experiments for the removal of cadmium(II) and copper(II). Results showed that uptake of Cd(II) and Cu(II) was unaffected by increases in pH (3.0 to 8.5) or concentration (1 to 20 mg/L). Increased ionic strength (from 0.001 to 1 M NaNO3), however, significantly affected the uptake of Cd(II); adsorption of Cu(II) was not affected. Freundlich adsorption isotherm results indicated that MCAC possessed higher sorption capacity than activated carbon. Second-order rate constants were found to be 0.0386 for activated carbon and 0.0633 g/mg x min for MCAC for Cd(II) and 0.0774 for AC and 0.1223 g/mg x min for MCAC for Cu(II). Column experiments showed that maximum sorption capacity of MCAC was 39.48 mg/g for Cu(II) and 12.21 mg/g for Cd(II). PMID- 22073736 TI - Assessment of internal and external grease interceptor performance for removal of food-based fats, oil, and grease from food service establishments. AB - A research study was performed to determine the fats, oil, and grease (FOG) removal efficiency of internal flow-based grease interceptors (FGI). A passive flow and a mechanical-flow FGI unit were tested and their performance was compared to an external retention-based grease interceptor (RGI). Experiments involved multiple parameters including three oil/water emulsion strengths, two influent liquid temperatures, and two flow rates. Overall, the RGI achieved approximately 80% FOG removal and the FGIs removed less than 50% under the tested conditions. One exception occurred during the passive FGI testing during which removal reached approximately 80%. This increased efficiency was likely due to the relatively weak emulsion exhibiting significantly large FOG globules. The FOG removal efficiency decreased with increased temperature because of increased breakage of FOG globules at the elevated temperature. These results suggest that emulsion strength significantly affects FOG removal efficiency of FGIs and should be considered in future manufacturer testing protocol. PMID- 22073737 TI - Career progression is not without prejudice. PMID- 22073738 TI - Trusts given support to create a fairer NHS for staff and patients. PMID- 22073739 TI - 'Staff will have greater awareness of individual needs'. PMID- 22073740 TI - A history that lives on. AB - The contribution of Florence Nightingale and Mary Seacole was immense. Their similarities and differences are described in this article. PMID- 22073741 TI - Breaking through barriers. AB - Jamaican-born public health nurse Yinglen Butt has held senior positions in NHS trusts and at the Department of Health. She says race has never been a barrier in her career and urges nurses to 'push against doors' to get where they want to be. PMID- 22073742 TI - Regulation resistance. AB - Nurses in France are unhappy with their working conditions and have responded with suspicion to a new body set up to regulate them. The Ordre National des Infirmiers has struggled to attract registrants, but there are signs of improvement. PMID- 22073743 TI - Targeted screening. AB - African-Caribbean men are at a higher risk of prostate cancer and should be encouraged to seek screening and have urinary problems investigated without delay. PMID- 22073744 TI - Raising awareness of borderline personality disorder and self-injury. AB - People with personality disorders frequently present to general health services. A large proportion of people with borderline personality disorder will self injure and seek physical clinical interventions from adult or practice nurses. These patients are often excluded from services and are highly stigmatised both in mental health services and the wider society. This article aims to increase the awareness of borderline personality disorder and self-injury among non-mental health nurses to assist them to work more effectively with patients who present with these difficulties. PMID- 22073745 TI - Palliative care for patients with chronic respiratory disease. AB - The article provides an overview of the key issues relating to palliative care for patients with chronic respiratory disease. The need for palliative care in this patient group is identified and the illness trajectory considered. Issues of communication, provision of palliative care services and symptom management are discussed and the need for improved services highlighted. PMID- 22073746 TI - Asthma: pathophysiology, diagnosis and management. AB - This article provides an overview of asthma in adults, includin pathophysiology, risk factors and triggers. Assessment, diagn pharmacological therapies are considered. The importance of in partnership with the patient and encouraging supported self-care are highlighted. PMID- 22073747 TI - Metastatic breast cancer. PMID- 22073748 TI - Why I decided to go private. PMID- 22073749 TI - Sickle cell: it's in the blood. PMID- 22073750 TI - Badge of honour. PMID- 22073751 TI - The logic of physiognomony in the late Renaissance. AB - This article studies the advances made in the logic of Renaissance physiognomy from the state of the subject in antiquity and the Middle Ages. The properties and accidents of the human body are investigated in the context of the signs selected by physiognomers, whether univocal or in syndromes, strong or weak in character, negative or positive, consistent with each other or contradictory. When these signs are translated into propositions, the construction of argument which flows from them is shown to be ut plurimum reasoning, in which an element of quasi-mathematical proto-probability and hermeneutical thinking (in the treatment of ambiguity and obscurity) may be detected. These allow the question "is x more likely to be the case than y or z?" to be answered through a variety of procedures. Renaissance physiognomy is shown to be a discipline in which a novel combination of rational procedures come together, and a site of conceptual change in respect of property and accidence. PMID- 22073752 TI - Two Pahlavi chapters on medicine. AB - The medical sciences in Sasanian society, in late Antiquity, constitute a rather neglected field of inquiry. Our most reliable sources for the study of this particular period in the history of science include a number of texts that were written in several older Iranian languages. In the following pages, we offer translations and commentaries on two such texts, written in Middle Persian, dealing with the life sciences. The topics discussed include copulation, pregnancies in various species, lactation, and moral and physical characteristics in the offspring. Placed in juxtaposition, the two texts, furthermore, clarify some of the obscure points in each of them. It is hoped that this preliminary study will help to sketch the path for future studies of the field. PMID- 22073753 TI - [Who did the first arterial ligation?]. AB - It is usual to bestow on Ambroise Pare the discovery of arterial ligation. He himself substantiates this assumption describing how he discovered it on the battlefield. But the survey of the surgical literature lets us see that in France, Guy de Chauliac and Henri de Mondeville had already described it and performed it. And, before them, the Italian surgeons of the 13th and 12th centuries. It was also well known by the Arab speaking surgeons who detained the translations of the Greek medical authors of the Antiquity. And indeed the description is to be found in Paul ofAegina and Oribasius. But it is in Celsus's De re medica that we find the first description. It may be reasonably assumed that it is much oldest. PMID- 22073754 TI - [Maternal imagination and congenital malformations]. AB - Since antiquity philosophers and scientists tried to explain the cause of congenital malformations. In early modern medicine maternal imagination was largely accepted as their true cause, This concept was rejected by Blondel, a London physician. Around 1750 Wolff introduced the Hemmungsbildung as the cause of congenital malformations, a concept adopted in 1781 by Blumenbach. Later on Soemmerring (1784), Crichton (1785) and Meckel the younger adopted Blumenbach's concept. In 1824 Suringar further developed it. More and more the excessive development of fetal blood vessels or nerves was rejected as a possible cause, although from time to time these ideas were adopted again. In the early 1800s Etienne Geoffroy Saint-Hilaire (1811) and Vrolik (1817) developed a classification of monstra. These attempts urged Isidore Geoffroy Saint-Hilaire (Etienne's son) and Vrolik the younger (Gerard's son) to develop it further. Nevertheless, around 1840 Vrolik had to admit that although we are well acqainted with the various malformations, we are still ignorant of the primary cause of these phenomena. Meanwhile the dispute between the adherents of the theory of preformation and those who had adopted the concept of epigenesis exercised many minds. In the second half of the eighteenth century the latter theory became more and more adopted and this fact cleared the way for the ideas introduced by Wolff and Blumenbach, because it was consistent with the idea of a gradual development of fetal structures. PMID- 22073755 TI - [History of phrenology]. AB - Gall & his supporters had intuition that brain was made up with functional areas but they did not correctly place them. This false science brought nothing to medicine but it left its mark on 19th century literature. However it contributed to introducing the notion of mitigating circumstances in the legal proceeding and set up basis of professional recruitment. It left plenty of technical gears: crane casting, china busts, phrenological penholders, knobs, craniological snuffboxes and a lot of geographic maps of the skull bumps. PMID- 22073756 TI - [The Ethics and Deontology division of the French National Council of Medical Doctors, eight years of activity, 1993-2001]. AB - The activity of the division of Ethics and deontology of the French National council of medical doctors is analysed by its former president (1993-2001). Among a lot of topics, a new version of the professionnal Code of deontology and patients' information were the main subjects of reflection and action. PMID- 22073757 TI - [The unicorn and the unicorn horn among apothecaries and physicians]. AB - In the 4th century A.D. the first unicorn was shown as a little horse with a twisted horn and was completely different from the Oriental one described by Marco Polo. The new unicorn appeared during the 4th century A.D. in Alexandria. This animal enamoured of purity was used as a Christian symbol of purity and sacrifice and adornment of churches like in Lyons in the 13th century. In the 15th & 17th centuries the unicorn was found again in famous tapestries like La Dame B la Licorne as it meant courage, speed and purity. Since the 6th century the powder of unicorn horn was used as a medicine or a drug against poisoning. Depictions of unicorn can be found in chemist's signs, engravings or paintings until the 19th century. PMID- 22073758 TI - [The Piscine Probatica, a painted canvas of the Hotel-Dieu of Rheims, documentation of an epidemic at the end of the 15th century]. AB - The Piscina Probatica theme is the highly distinctive iconography in an impressive painted canvas from the ancient Rheims hotel-Dieu, dating back to the late 15th or early 16th century. In the first place, it is interesting to note that the actual site of the pool has been located, so that archaeological findings bring confirmation to testament scriptures. Through the choice of the painted-canvas medium, and thanks to his great pictorial skill, the anonymous Rheims artist has given us a document of exceptional value, concerning the signs and symptoms of an illness which wrought havoc in the Rheims area in his own lifetime, namely ignis plaga or "mal des ardents". Other great artists of the same period, such as J. Bosch, have testified to the horror of the illness. As a matter-of-fact, the illness has been fully documented, from the 17th century onwards, and the medical expert H.A. Tessier, also acting as an agricultural expert, has demonstrated that ergotized rye is responsible for the fatal condition known as ergotism, and for the heavy toll it has levied on human lives in the course of centuries. PMID- 22073759 TI - [The intervention of the Royal College of Medicine in Nancy in the regulation of pharmaceutical activity]. AB - Created in 1752 the Royal College of Medicine in Nancy constituted an institution with extended powers, particularly in sanitary policy and pharmaceutical activity. After explaining the rules of the College, the paper describes with examples its participation to the examinations of pharmacy pupils and their sustaining of "Conclusions de pharmacie et de chymie", to the delivery of drugs and to the fight against charlatanry and prohibited activity of pharmacy. From its creating to its disparition in 1793 by order of the government, the Royal College of Medicine worked remarkably, and the rules worked up during the forty years of its life appear to be of a great modernity. PMID- 22073760 TI - [Medicinal plants and symbols in the medieval mystic altarpiece]. AB - The medieval mystic altarpiece towers above the altar table. It is linked to the evocation of a religious mystery beyond our faculty of reasoning. Symbolism of an enclosed garden evokes the image of the Heavenly Garden isolated by a wall from the rest of earthly world. In this mystic chiefly Rhenan altarpiece the enclosed garden is that of Virgin Mary who in the Middle Ages was likened to the spouse in the song of songs. The Blessed Virgin is painted with flowers, lily, rose, violet, lily of the valley. Most of these are medicinal plants in order to implore a faith healing for the believers. All in all about fifty plants are showed on Rhenan altarpieces and on 14th century mystic altarpieces almost contemporary of Issenheim's altarpiece, some Italian, some Rhenan. PMID- 22073761 TI - A follow-up study of patients with medically unexplained symptoms referred to a liaison psychiatry service. AB - OBJECTIVE: The principal objective was to describe general hospital use and mortality in a group of patients with medically unexplained symptoms referred to a liaison psychiatry service. METHOD: Cases were identified from patients with medically unexplained symptoms referred to a liaison psychiatry service between 1998 and 2005. We also identified a control group of patients, matched for age, sex, and date of referral, referred for other reasons to the same service. Follow up information was obtained from the New Zealand Health Information Service national minimum data set from 1998 to 2006. Finally we compared hospital use in people with medically unexplained symptoms with national data on average length of stay in New Zealand hospitals. RESULTS: Over 9 years 153 patients referred for medically unexplained symptoms spent nearly 14,000 days in hospital. They also had statistically significant greater numbers of general hospital admissions and fewer deaths compared to patients referred to liaison psychiatry for other reasons. Patients with medically unexplained symptoms spent 41% spent longer in hospital on each admission (5.5 days) compared to the New Zealand average length of stay in general hospitals (3.9 days). After referral to liaison psychiatry patients who were frequently admitted with medically unexplained symptoms experienced a statistically significant decrease in the number of admissions and length of stay per year. CONCLUSIONS: Patients referred to a liaison psychiatry service with medically unexplained symptoms use substantial amounts of health service resources. They also have a lower mortality and are admitted to hospital more often than a matched control group. PMID- 22073762 TI - The treatment of patients with medically unexplained physical symptoms in China: a study comparing expectations and treatment satisfaction in psychosomatic medicine, biomedicine, and traditional Chinese medicine. AB - OBJECTIVE: Little is known about treatment for patients with medically unexplained symptoms (MUS) in China. This study investigates the treatment expectations and treatment satisfaction of patients with MUS in psychosomatic medicine, biomedicine, and Traditional Chinese Medicine (TCM). METHOD: In a cross sectional survey, n = 96 (10.3%) out of 931 participating patients were screened positive for multiple somatoform symptoms. These patients answered questionnaires concerning symptom duration, number of doctor visits, functional impairment, emotional distress, treatment expectations, treatment satisfaction, and empathy in the consultation. The physicians filled in a questionnaire about applied or recommended treatment. RESULTS: Most of the patients from psychosomatic medicine wanted psychotherapy. In TCM, 55% of the patients had already received TCM treatment and most of them wanted to continue TCM treatment. Patients in biomedicine did not express clear expectations; most of them had had no previous treatment. A combination of treatment methods was most prevalent in biomedicine in comparison to psychosomatic medicine and TCM. The outcome from the patients' point of view was significantly better in TCM than in psychosomatic medicine and biomedicine. Psychosomatic medicine's strength was the empathetic physician patient interaction. CONCLUSIONS: From a biopsychosocial perspective, these results suggest that various treatment approaches with various emphases can be effective depending on the patient's complaints, his illness beliefs, and what the physician offers. The results will be verified in a larger multicenter longitudinal study. PMID- 22073763 TI - Schizophrenia: medical illness, mortality, and aging. AB - OBJECTIVE: Schizophrenia is a devastating and common psychiatric disorder which is associated with a high degree of medical morbidity and reduced life span in addition to psychosis. In this article, these problems will be discussed in the context of schizophrenia and aging. METHOD: The recent literature was reviewed using Pubmed, Medline, and Google scholar with the search terms "schizophrenia, aging, medical problems." RESULTS: Schizophrenia is associated with significant medical morbidity and mortality. Diabetes and cardiovascular disease, along with smoking and obesity, are over-represented and contribute to reduced quality of life and life span. Schizophrenics often receive poor medical care. CONCLUSIONS: The impacts of schizophrenia on physical health and successful aging have been underestimated. Psychiatrists and primary care physicians need to address the overlapping medical and psychiatric aspects of the disorder while the medical care system for these patients requires a much higher degree of coordination than is currently available. PMID- 22073764 TI - A brief measure of core religious beliefs for use in psychiatric settings. AB - Results from several national studies in the United States suggests that: (1) religious beliefs and practices are highly prevalent; (2) spirituality and religion are statistically and clinically relevant to mental health and symptoms; and (3) many patients have a preference for spiritually integrated care. However, existing protocols that assess for salient religious themes in psychiatric settings are time-consuming to administer, relevant only to specific populations (e.g., Christians), and have poor psychometric properties. Further, evidence suggests that religious beliefs can take on a positive and negative valence, and both of these dimensions are worthy of assessment. We, therefore, developed a brief (six-item) self-report measure of positive and negative core beliefs about God which is uniquely suited for use with a broad range of religious patients. Across three studies, we evaluated its psychometric properties and ability to predict symptoms of anxiety and depression. Results provide support for the validity and reliability of our measure and further highlight the salience of both positive and negative religious beliefs to psychiatric symptoms. It is hoped that this measure will help to decrease the burden of spiritual assessment in psychiatric and medical settings, and further have research utility for this area of study. PMID- 22073765 TI - The mind-body connection: an integrated approach to the diagnosis of colonic trichobezoar. AB - The relationship between trichophagia, the compulsive eating of hair, and trichobezoar, the accumulation of hair within the gastrointestinal tract, illustrates the importance of the mind-body connection. Physicians ought to be cognizant of this association in the evaluation of colonic obstruction as colonic trichobezoars, though uncommon, carry a high mortality rate. Incorporation of the psychiatric and dermatological examinations is a simple way to raise clinical suspicion for the presence of a trichobezoar, and to prompt early and appropriate surgical treatment. Even after resolution, treatment of the underlying trichophagia is highly recommended to prevent future complications. PMID- 22073766 TI - Active depression is associated with regional adiposity in the upper abdomen and the neck. AB - OBJECTIVE: In major depression, the incidence of overweight, the risk of type 2 diabetes, as well as cardiovascular disease is increased. Aim was to determine body fat distribution in depressive and healthy females using whole body Magnetic Resonance Imaging (MRI). Measurements of total adipose tissue (TAT), visceral (VAT), and subcutaneous adipose tissue (SCAT) at the trunk and the whole body fat distribution along the body axis were performed and compared. Differences in body fat distribution between depressive and healthy females and their location were evaluated. METHODS: In total, 11 women with a depressive syndrome (major depression, MD) and 45 healthy female volunteers (HC) matched for age and body mass index were compared. Total tissue (TT), TAT, VAT, and SCAT were quantified using T1-weighted whole body MRI. Adipose tissue distribution was compared along the body axis. RESULTS: MD patients showed higher adipose tissue volumes than the HC group. Especially in the upper abdomen, at the upper extremities and the neck, MD patients are characterized by a significantly higher adipose tissue mass compared to the HC group. CONCLUSIONS: The results of this study confirm the hypothesis of a high stress level with a disturbed hypothalamic-pituitary-adrenal (HPA) axis leading to a Cushing-like habitus and high visceral fat levels. The increased fat levels at the arms, as well as the whole body fat may be well founded by a lack of activity in depression. These effects should be evaluated in further longitudinal studies investigating patients with a depressive syndrome and after remission. PMID- 22073768 TI - Inspiration in the harness of daily labor. Darwin, botany, and the triumph of evolution, 1859-1868. AB - Charles Darwin hoped that a large body of working naturalists would embrace evolution after the Origin of Species appeared in late 1859. He was disappointed. His evolutionary ideas at first made painfully little progress in the scientific community. But by 1863 the tide had turned dramatically, and within five years evolution became scientific orthodoxy in Britain. The Origin's reception followed this peculiar trajectory because Darwin had not initially tied its theory to productive original scientific investigation, which left him vulnerable to charges of reckless speculation. The debate changed with his successful application of evolution to original problems, most notably orchid fertilization, the subject of a well-received book in 1862. Most of Darwin's colleagues found the argument of the Origin convincing when they realized that it functioned productively in the day-to-day work of science-and not before. The conceptual force of the Origin, however outwardly persuasive, acquired full scientific legitimacy only when placed "in the harness of daily labour". PMID- 22073767 TI - Quality of life in postmenopausal women: the impact of depressive and anxiety disorders. AB - OBJECTIVE: Psychiatric symptoms are frequently present in postmenopausal women. The present study aimed to investigate the impact of depressive and anxiety disorders on the quality of life (QoL) of postmenopausal women. METHOD: The study sample consisted of 342 postmenopausal women who presented to the Gynecology Outpatient Clinic. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was used to determine depressive and anxiety disorders. The participants' QoL level was assessed by means of the World Health Organization QoL Assessment-Brief (WHOQOL-BREF). RESULTS: Subjects without a diagnosis of depressive or anxiety disorder had significantly higher points in all domains of WHOQOL-BREF. According to linear regression analysis, all evaluated disorders except social phobia and specific phobia were independently associated with lower scores for at least one dimension of the QoL scale. However, major depression, dysthymic disorder, and generalized anxiety disorder predicted all domains of WHOQOL-BREF. CONCLUSION: Depressive and anxiety disorders, particularly major depression, dysthymic disorder, and generalized anxiety disorder, seem to be considerable factors affecting the QoL in postmenopausal women. PMID- 22073769 TI - Trading in birds: imperial power, national pride, and the place of nature in U.S. Colombia relations. AB - Between the 1910s and the 1940s, American naturalists carried out a number of ornithological expeditions in Colombia. With the help of Colombian naturalists, thousands of skins were brought to natural history museums in the United States. By 1948 these birds had become an important treasure: American ornithologists declared Colombia the nation with the most bird species. This story sheds new light on the role science played in the expansion of U.S. political, economic, and cultural influence in Latin America in the early twentieth century, as well as on the relation between nationalist movements in Latin America and the study of the natural world. Recognizing a complex but fruitful interaction between nationalist policies and imperial practices proves important for understanding the success of the naturalists' enterprise in Colombia. PMID- 22073770 TI - Who owns what? Private ownership and the public interest in recombinant DNA technology in the 1970s. AB - This essay analyzes how academic institutions, government agencies, and the nascent biotech industry contested the legal ownership of recombinant DNA technology in the name of the public interest. It reconstructs the way a small but influential group of government officials and university research administrators introduced a new framework for the commercialization of academic research in the context of a national debate over scientific research's contributions to American economic prosperity and public health. They claimed that private ownership of inventions arising from public support would provide a powerful means to liberate biomedical discoveries for public benefit. This articulation of the causal link between private ownership and the public interest, it is argued, justified a new set of expectations about the use of research results arising from government or public support, in which commercialization became a new public obligation for academic researchers. By highlighting the broader economic and legal shifts that prompted the reconfiguration of the ownership of public knowledge in late twentieth-century American capitalism, the essay examines the threads of policy-informed legal ideas that came together to affirm private ownership of biomedical knowledge as germane to the public interest in the coming of age of biotechnology and genetic medicine. PMID- 22073771 TI - The skeleton in the closet: should historians of science care about the history of mathematics? AB - Up until the 1950s, the history of mathematics was an integral part of the history of science. To George Sarton and his contemporaries, mathematics was the rational skeleton that organized science and held it together, and its history was a fundamental component of the broader history of science. But when historians began focusing on the cultural roots of science rather than its rational structure, the study of mathematics was marginalized and ultimately excluded from the history of science. The alienation between the two fields is detrimental to both, and in recent years there has been a sustained effort to reestablish meaningful communication between the two. This time, however, mathematics is seen not as the static skeleton of science but, instead, as a dynamic and historically evolving field in its own right-just like science itself. The new approach allows for a culturally sensitive study of mathematics, as well as a new and fruitful relationship between the history of science and the history of mathematics. The essays in this Focus section offer a sampling of the new approaches, opening the way to a rapprochement between fields that have gone their separate ways but should by rights be closely interconnected. PMID- 22073772 TI - Between timelessness and historiality: on the dynamics of the epistemic objects of mathematics. AB - In order to discuss the temporal structure of mathematical research, this essay offers four related definitions of a mathematical object from different times and places. It is argued that in order to appreciate the differences between these definitions, the historian needs to understand that none of them made sense in mathematical practice without a technical framework, referred to but not explained in the definitions themselves (an "epistemic configuration of research"); that the dynamics of the epistemic objects of mathematical research are secondary to the dynamics of these epistemic configurations as a whole; and that the dynamics of epistemic configurations of mathematical research do not follow law-like processes. Very different types of change may happen, and some of them link the dynamics of epistemic configurations with events and developments far beyond the bounds of the research field in question. These insights have historiographical consequences that require us to rethink the kind of temporality ascribed to mathematics. PMID- 22073773 TI - AfterMath: the work of proof in the age of human-machine collaboration. AB - During the 1970s and 1980s, a team of Automated Theorem Proving researchers at the Argonne National Laboratory near Chicago developed the Automated Reasoning Assistant, or AURA, to assist human users in the search for mathematical proofs. The resulting hybrid humans+AURA system developed the capacity to make novel contributions to pure mathematics by very untraditional means. This essay traces how these unconventional contributions were made and made possible through negotiations between the humans and the AURA at Argonne and the transformation in mathematical intuition they produced. At play in these negotiations were experimental practices, nonhumans, and nonmathematical modes of knowing. This story invites an earnest engagement between historians of mathematics and scholars in the history of science and science studies interested in experimental practice, material culture, and the roles of nonhumans in knowledge making. PMID- 22073774 TI - "This compendious language": mathematics in the world of Augustus De Morgan. AB - Mathematics is the most chameleon of subjects, whose meaning is differently defined in different circumstances. This essay considers the mathematics of Augustus De Morgan as an illustration of the ways that the essence of the subject, the very objects that are included within it, has been adjusted in response to cultural factors. Since these cultural factors are the same ones that shape scientific development, the argument is that the history of mathematics and the history of science are always inextricably bound to one another. PMID- 22073775 TI - History of mathematics and history of science reunited? AB - For some years now, the history of modern mathematics and the history of modern science have developed independently. A step toward a reunification that would benefit both disciplines could come about through a revived appreciation of mathematical practice. Detailed studies of what mathematicians actually do, whether local or broadly based, have often led in recent work to examinations of the social, cultural, and national contexts, and more can be done. Another recent approach toward a historical understanding of the abstractness of modern mathematics has been to see it as a species of modernism, and this thesis will be tested by the raft of works on the history of modern applied mathematics currently under way. PMID- 22073776 TI - History of mathematics and history of science. AB - This essay argues that the diversity of the history of mathematics community in the United Kingdom has influenced the development of the subject and is a significant factor behind the different concerns often evident in work on the history of mathematics when compared with that of historians of science. The heterogeneous nature of the community, which includes many who are not specialist historians, and the limited opportunities for academic careers open to practitioners have had a profound effect on the discipline, leading to a focus on elite mathematics and great mathematicians. More recently, reflecting earlier developments in the history of science, an increased interest in the context and culture of the practice of mathematics has become evident. PMID- 22073777 TI - Experimental evidence for mediation of competition by habitat succession. AB - Habitat succession is thought to influence the importance of competition in assemblages. Competitive interactions are considered of critical importance in structuring ant assemblages, but field experiments show varied effects. I tested how succession in managed boreal forests affects the outcome of competition from dominant red wood ants, Formica aquilonia, through a removal experiment in replicated stands of three different ages (0-4, 30-40, and 80-100 years old). F. aquilonia abundance was reduced by 87%, and procedural controls showed no nontarget effects. The succession gradient revealed the full range of possible responses from ant species: decreases in 1-4-year-old stands, increases in 30-40 year-old stands, and no effects in 80-100-year-old stands, where diversity was lowest. Habitat succession thus regulates competitive interactions in this system. I propose a model for this system, where competitive effects depend on time since disturbance. In this case, soon after disturbance the dominant species facilitates increases in the abundance of other species. At intermediate times, competition reduces the abundance of some species. Finally, in long-undisturbed habitats, competitors may fail to evolve, particularly in high-stress environments. Interactions between competition and habitat succession may explain why structuring effects of ecologically dominant species appear inconsistent. PMID- 22073778 TI - A power analysis for multivariate tests of temporal trend in species composition. AB - Long-term monitoring programs emphasize power analysis as a tool to determine the sampling effort necessary to effectively document ecologically significant changes in ecosystems. Programs that monitor entire multispecies assemblages require a method for determining the power of multivariate statistical models to detect trend. We provide a method to simulate presence-absence species assemblage data that are consistent with increasing or decreasing directional change in species composition within multiple sites. This step is the foundation for using Monte Carlo methods to approximate the power of any multivariate method for detecting temporal trends. We focus on comparing the power of the Mantel test, permutational multivariate analysis of variance, and constrained analysis of principal coordinates. We find that the power of the various methods we investigate is sensitive to the number of species in the community, univariate species patterns, and the number of sites sampled over time. For increasing directional change scenarios, constrained analysis of principal coordinates was as or more powerful than permutational multivariate analysis of variance, the Mantel test was the least powerful. However, in our investigation of decreasing directional change, the Mantel test was typically as or more powerful than the other models. PMID- 22073779 TI - On the use of log-transformation vs. nonlinear regression for analyzing biological power laws. AB - Power-law relationships are among the most well-studied functional relationships in biology. Recently the common practice of fitting power laws using linear regression (LR) on log-transformed data has been criticized, calling into question the conclusions of hundreds of studies. It has been suggested that nonlinear regression (NLR) is preferable, but no rigorous comparison of these two methods has been conducted. Using Monte Carlo simulations, we demonstrate that the error distribution determines which method performs better, with NLR better characterizing data with additive, homoscedastic, normal error and LR better characterizing data with multiplicative, heteroscedastic, lognormal error. Analysis of 471 biological power laws shows that both forms of error occur in nature. While previous analyses based on log-transformation appear to be generally valid, future analyses should choose methods based on a combination of biological plausibility and analysis of the error distribution. We provide detailed guidelines and associated computer code for doing so, including a model averaging approach for cases where the error structure is uncertain. PMID- 22073780 TI - Monotonicity-constrained species distribution models. AB - Flexible modeling frameworks for species distribution models based on generalized additive models that allow for smooth, nonlinear effects and interactions are of increasing importance in ecology. Commonly, the flexibility of such smooth function estimates is controlled by means of penalized estimation procedures. However, the actual shape remains unspecified. In many applications, this is not desirable as researchers have a priori assumptions on the shape of the estimated effects, with monotonicity being the most important. Here we demonstrate how monotonicity constraints can be incorporated in a recently proposed flexible framework for species distribution models. Our proposal allows monotonicity constraints to be imposed on smooth effects and on ordinal, categorical variables using an additional asymmetric L2 penalty. Model estimation and variable selection for Red Kite (Milvus milvus) breeding was conducted using the flexible boosting framework implemented in R package mboost. PMID- 22073781 TI - Intraspecific trait variants determine the nature of interspecific interactions in a habitat-forming species. AB - Although the study of ecological interactions often takes into account functional variation between species, intraspecific variation is commonly ignored. Here, we investigate the importance of an intraspecific polymorphism in shaping interspecific interactions in a habitat-building species. Colonies of the social spider Anelosimus studiosus provide habitat for dozens of arthropod species, and colony members exhibit markedly polymorphic behavioral temperaments (BT): "aggressive" or "docile." We manipulated the phenotypic compositions of colonies (100% aggressive, 50% aggressive and 50% docile, 100% docile) and measured the nature and magnitude of interactions between A. studiosus and two heterospecific web associates, Larinioides cornutus and Agelenopsis emertoni. We found that BT composition significantly affected the outcome of interspecific interactions, changing the relationship between A. studiosus and its web associates from an ammensalism (where A. studiosus experiences reduced fecundity and survival) to a commensalism or mutualism. Our study successfully illustrates the potential of BTs to impact whole community dynamics, and conversely, for community structure to influence the maintenance of BTs. PMID- 22073782 TI - Plasticity in foraging strategies of inshore birds: how Little Penguins maintain body reserves while feeding offspring. AB - Breeding animals face important time and energy constraints when caring for themselves and their offspring. For long-lived species, life-history theory predicts that parents should favor survival over current reproductive attempts, thus investing more into their own maintenance than the provisioning of their young. In seabirds, provisioning strategies may additionally be influenced by the distance between breeding sites and foraging areas, and offshore and inshore species should thus exhibit different strategies. Here, we examine the provisioning strategies of an inshore seabird using a long-term data set on more than 200 Little Penguins, Eudyptula minor. They alternated between two consecutive long and several short foraging trips all along chick rearing, a strategy almost never observed for inshore animals. Short trips allowed for regular provisioning of the chicks (high feeding frequency and larger meals), whereas long trips were performed when parent body mass was low and enabled them to rebuild their reserves, suggesting that adult body condition may be a key factor in initiating long trips. Inshore seabirds do use dual strategies of alternating short and long trips, but from our data, on a simpler and less flexible way than for offshore birds. PMID- 22073783 TI - Climate, icing, and wild arctic reindeer: past relationships and future prospects. AB - Across the Arctic, heavy rain-on-snow (ROS) is an "extreme" climatic event that is expected to become increasingly frequent with global warming. This has potentially large ecosystem implications through changes in snowpack properties and ground-icing, which can block the access to herbivores' winter food and thereby suppress their population growth rates. However, the supporting empirical evidence for this is still limited. We monitored late winter snowpack properties to examine the causes and consequences of ground-icing in a Svalbard reindeer (Rangifer tarandus platyrhynchus) metapopulation. In this high-arctic area, heavy ROS occurred annually, and ground-ice covered from 25% to 96% of low-altitude habitat in the sampling period (2000-2010). The extent of ground-icing increased with the annual number of days with heavy ROS (> or = 10 mm) and had a strong negative effect on reindeer population growth rates. Our results have important implications as a downscaled climate projection (2021-2050) suggests a substantial future increase in ROS and icing. The present study is the first to demonstrate empirically that warmer and wetter winter climate influences large herbivore population dynamics by generating ice-locked pastures. This may serve as an early warning of the importance of changes in winter climate and extreme weather events in arctic ecosystems. PMID- 22073784 TI - Evolution of a stream ecosystem in recently deglaciated terrain. AB - Climate change and associated glacial recession create new stream habitat that leads to the assembly of new riverine communities through primary succession. However, there are still very few studies of the patterns and processes of community assembly during primary succession for stream ecosystems. We illustrate the rapidity with which biotic communities can colonize and establish in recently formed streams by examining Stonefly Creek in Glacier Bay, Alaska (USA), which began to emerge from a remnant glacial ice mass between 1976 and 1979. By 2002, 57 macroinvertebrate and 27 microcrustacea species had become established. Within 10 years of the stream's formation, pink salmon and Dolly Varden charr colonized, followed by other fish species, including juvenile red and silver salmon, Coast Range sculpin, and sticklebacks. Stable-isotope analyses indicate that marine derived nitrogen from the decay of salmon carcasses was substantially assimilated within the aquatic food web by 2004. The findings from Stonefly Creek are compared with those from a long-term study of a similarly formed but older stream (12 km to the northeast) to examine possible similarities in macroinvertebrate community and biological trait composition between streams at similar stages of development. Macroinvertebrate community assembly appears to have been initially strongly deterministic owing to low water temperature associated with remnant ice masses. In contrast, microcrustacean community assembly appears to have been more stochastic. However, as stream age and water temperature increased, macroinvertebrate colonization was also more stochastic, and taxonomic similarity between Stonefly Creek and a stream at the same stage of development was <50%. However the most abundant taxa were similar, and functional diversity of the two communities was almost identical. Tolerance is suggested as the major mechanism of community assembly. The rapidity with which salmonids and invertebrate communities have become established across an entire watershed has implications for the conservation of biodiversity in freshwater habitats. PMID- 22073785 TI - Patterns of body mass senescence and selective disappearance differ among three species of free-living ungulates. AB - Declines in survival and reproduction with age are prevalent in wild vertebrates, but we know little about longitudinal changes in behavioral, morphological, or physiological variables that may explain these demographic declines. We compared age-related variation in body mass of adult females in three free-living ungulate populations that have been the focus of long-term, individual-based research: bighorn sheep (Ovis canadensis) at Ram Mountain, Canada; roe deer (Capreolus capreolus) at Trois Fontaines, France; and Soay sheep (Ovis aries) on St. Kilda, Scotland. We use two recently proposed approaches to separate contributions to age-dependent variation at the population level from within-individual changes and between-individual selective disappearance. Selective disappearance of light individuals in all three populations was most evident at the youngest and oldest ages. In later adulthood, bighorn sheep and roe deer showed a continuous decline in body mass that accelerated with age while Soay sheep showed a precipitous decrease in mass in the two years preceding death. Our results highlight the importance of mass loss in explaining within-individual demographic declines in later adulthood in natural populations. They also reveal that the pattern of senescence, and potentially also the processes underlying demographic declines in late life, can differ markedly across related species with similar life histories. PMID- 22073786 TI - Size-mediated non-trophic interactions and stochastic predation drive assembly and dynamics in a seabird community. AB - Theoretical and empirical evidence suggests that body size is a major life history trait impacting on the structure and functioning of complex food webs. However, long-term analyses of size-dependent interactions within simpler network modules, for instance, competitive guilds, are scant. Here, we model the assembly dynamics of the largest breeding seabird community in the Mediterranean basin during the last 30 years. This unique data set allowed us to test, through a "natural experiment," whether body size drove the assembly and dynamics of an ecological guild growing from very low numbers after habitat protection. Although environmental stochasticity accounted for most of community variability, the population variance explained by interspecific interactions, albeit small, decreased sharply with increasing body size. Since we found a demographic gradient along a body size continuum, in which population density and stability increase with increasing body size, the numerical effects of interspecific interactions were proportionally higher on smaller species than on larger ones. Moreover, we found that the per capita interaction coefficients were larger the higher the size ratio among competing species, but only for the set of interactions in which the species exerting the effect was greater. This provides empirical evidence for long-term asymmetric interspecific competition, which ultimately prompted the local extinction of two small species during the study period. During the assembly process stochastic predation by generalist carnivores further triggered community reorganizations and global decays in population synchrony, which disrupted the pattern of interspecific interactions. These results suggest that the major patterns detected in complex food webs can hold as well for simpler sub-modules of these networks involving non-trophic interactions, and highlight the shifting ecological processes impacting on assembling vs. asymptotic communities. PMID- 22073787 TI - Influence of corallivory, competition, and habitat structure on coral community shifts. AB - The species composition of coral communities has shifted in many areas worldwide through the relative loss of important ecosystem engineers such as highly branched corals, which are integral in maintaining reef biodiversity. We assessed the degree to which the performance of recently recruited branching corals was influenced by corallivory, competition, sedimentation, and the interactions between these factors. We also explored whether the species-specific influence of these biotic and abiotic constraints helps to explain recent shifts in the coral community in lagoons of Moorea, French Polynesia. Population surveys revealed evidence of a community shift away from a historically acroporid-dominated community to a pocilloporid- and poritid-dominated community, but also showed that the distribution and abundance of coral taxa varied predictably with location in the lagoon. At the microhabitat scale, branching corals grew mainly on dead or partially dead massive Porites ("bommies"), promontories with enhanced current velocities and reduced sedimentation. A demographic study revealed that growth and survival of juvenile Pocillopora verrucosa and Acropora retusa, the two most common branching species of each taxon, were affected by predation and competition with vermetid gastropods. By 24 months of age, 20-60% of juvenile corals suffered partial predation by corallivorous fishes, and injured corals experienced reduced growth and survival. A field experiment confirmed that partial predation by corallivorous fishes is an important, but habitat-modulated, constraint for branching corals. Competition with vermetid gastropods reduced growth of both branching species but unexpectedly also provided an associational defense against corallivory. Overall, the impact of abiotic constraints was habitat-specific and similar for Acropora and Pocillopora, but biotic interactions, especially corallivory, had a greater negative effect on Acropora than Pocillopora, which may explain the local shift in coral community composition. PMID- 22073788 TI - Evaluating the importance of demographic connectivity in a marine metapopulation. AB - Recently researchers have gone to great lengths to measure marine metapopulation connectivity via tagging, genetic, and trace-elemental fingerprinting studies. These empirical estimates of larval dispersal are key to assessing the significance of metapopulation connectivity within a demographic context, but the life-history data required to do this are rarely available. To evaluate the demographic consequences of connectivity we constructed seasonal, size-structured metapopulation matrix models for two species of mytilid mussel in San Diego County, California, USA. The self-recruitment and larval exchange terms were produced from a time series of realized connectivities derived from trace elemental fingerprinting of larval shells during spring and fall from 2003 to 2008. Both species exhibited a strong seasonal pattern of southward movement of recruits in spring and northward movement in fall. Growth and mortality terms were estimated using mark-recapture data from representative sites for each species and subpopulation, and literature estimates of juvenile mortality. Fecundity terms were estimated using county-wide settlement data from 2006-2008; these data reveal peak reproduction and recruitment in fall for Mytilus californianus, and spring for M. galloprovincialis. Elasticity and life-stage simulation analyses were employed to identify the season- and subpopulation specific vital rates and connectivity terms to which the metapopulation growth rate (lambda) was most sensitive. For both species, metapopulation growth was most sensitive to proportional changes in adult fecundity, survival and growth of juvenile stages, and population connectivity, in order of importance, but relatively insensitive to adult growth or survival. The metapopulation concept was deemed appropriate for both Mytilus species as exchange between the subpopulations was necessary for subpopulation persistence. However, highest metapopulation growth occurred in years when a greater proportion of recruits was retained within the predominant source subpopulation. Despite differences in habitat and planktonic duration, both species exhibited similar overall metapopulation dynamics with respect to key life stages and processes. However, different peak reproductive periods in an environment of seasonal current reversals led to different regional (subpopulation) contributions to metapopulation maintenance; this result emphasizes the importance of connectivity analysis for spatial management of coastal resources. PMID- 22073789 TI - Demographic heterogeneity, cohort selection, and population growth. AB - Demographic heterogeneity--variation among individuals in survival and reproduction--is ubiquitous in natural populations. Structured population models address heterogeneity due to age, size, or major developmental stages. However, other important sources of demographic heterogeneity, such as genetic variation, spatial heterogeneity in the environment, maternal effects, and differential exposure to stressors, are often not easily measured and hence are modeled as stochasticity. Recent research has elucidated the role of demographic heterogeneity in changing the magnitude of demographic stochasticity in small populations. Here we demonstrate a previously unrecognized effect: heterogeneous survival in long-lived species can increase the long-term growth rate in populations of any size. We illustrate this result using simple models in which each individual's annual survival rate is independent of age but survival may differ among individuals within a cohort. Similar models, but with nonoverlapping generations, have been extensively studied by demographers, who showed that, because the more "frail" individuals are more likely to die at a young age, the average survival rate of the cohort increases with age. Within ecology and evolution, this phenomenon of "cohort selection" is increasingly appreciated as a confounding factor in studies of senescence. We show that, when placed in a population model with overlapping generations, this heterogeneity also causes the asymptotic population growth rate lambda to increase, relative to a homogeneous population with the same mean survival rate at birth. The increase occurs because, even integrating over all the cohorts in the population, the population becomes increasingly dominated by the more robust individuals. The growth rate increases monotonically with the variance in survival rates, and the effect can be substantial, easily doubling the growth rate of slow-growing populations. Correlations between parent and offspring phenotype change the magnitude of the increase in lambda, but the increase occurs even for negative parent-offspring correlations. The effect of heterogeneity in reproductive rate on lambda is quite different: growth rate increases with reproductive heterogeneity for positive parent-offspring correlation but decreases for negative parent-offspring correlation. These effects of demographic heterogeneity on lambda have important implications for population dynamics, population viability analysis, and evolution. PMID- 22073790 TI - Forest annual carbon cost: comment. PMID- 22073792 TI - Why does nutrition deteriorate rapidly among children under 2 years of age? Using qualitative methods to understand community perspectives on complementary feeding practices in Bangladesh. AB - BACKGROUND: Child undernutrition remains high in South Asian and sub-Saharan African countries. Rapid declines in nutritional status occur before the age of 2 years, particularly during the period of complementary feeding. Improving complementary feeding practices is a neglected area in nutrition programs. OBJECTIVE: To understand community perspectives on complementary feeding practices in order to inform the design of future interventions for improved complementary feeding. METHODS: From May through August 2009, data were collected in two rural locations and one urban location in Bangladesh through semistructured interviews, food attributes exercises, 24-hour dietary recalls, opportunistic observations, and trials of improved practices (TIPs). Key informant interviews and focus group discussions were also carried out among family members and community opinion leaders. RESULTS: Lay perceptions about complementary feeding differ substantially from international complementary feeding recommendations. A large proportion of children do not consume sufficient amounts of complementary foods to meet their energy and micronutrient needs. There was a gap in knowledge about appropriate complementary foods in terms of quality and quantity and strategies to convert family foods to make them suitable for children. Complementary feeding advice from family members, peers, and health workers, the importance given to feeding young children, and time spent by caregivers in feeding influenced the timing, frequency, types of food given, and ways in which complementary feeding occurred. CONCLUSIONS: Perceptions and practices related to complementary feeding need to be effectively addressed to improve the levels of child undernutrition. Lack of understanding of children's nutritional needs and insufficient time for feeding children are key barriers to complementary feeding. PMID- 22073791 TI - Meat consumption is associated with less stunting among toddlers in four diverse low-income settings. AB - BACKGROUND: Early growth faltering is common but is difficult to reverse after the first 2 years of life. OBJECTIVE: To describe feeding practices and growth in infants and young children in diverse low-income settings prior to undertaking a complementary feeding trial. METHODS: This cross-sectional study was conducted through the Global Network for Women's and Children's Health Research in Guatemala, Democratic Republic of Congo, Zambia, and Pakistan. Feeding questionnaires were administered to convenience samples of mothers of 5- to 9 month old infants and 12- to 24-month-old toddlers. After standardized training, anthropometric measurements were obtained from the toddlers. Following the 2006 World Health Organization Growth Standards, stunting was defined as length-for age < -2SD, and wasting as weight-for-length < -2SD. Logistic regression was applied to evaluate relationships between stunting and wasting and consumption of meat (including chicken and liver and not including fish). RESULTS: Data were obtained from 1,500 infants with a mean (+/- SD) age of 6.9 +/- 1.4 months and 1,658 toddlers with a mean age of 17.2 +/- 3.5 months. The majority of the subjects in both age groups were breastfed. Less than 25% of the infants received meat regularly, whereas 62% of toddlers consumed these foods regularly, although the rates varied widely among sites. Stunting rate ranged from 44% to 66% among sites; wasting prevalence was less than 10% at all sites. After controlling for covariates, consumption of meat was associated with a reduced likelihood of stunting (OR = 0.64; 95% CI, 0.46 to 0.90). CONCLUSIONS: The strikingly high stunting rates in these toddlers and the protective effect of meat consumption against stunting emphasize the need for interventions to improve complementary feeding practices, beginning in infancy. PMID- 22073793 TI - On the transition to sustainability: an analysis of the costs of school feeding compared with the costs of primary education. AB - BACKGROUND: The current food, fuel, and financial crises have highlighted the importance of school feeding programs both as a social safety net for children living in poverty and food insecurity, and as part of national educational policies and plans. OBJECTIVE: To examine the costs of school feeding, in terms of both the absolute cost per child and the cost per child relative to overall education expenditure and gross domestic product (GDP) in low-, middle-, and high income countries. METHODS: Data on the costs of school feeding in different countries were collected from multiple sources, including World Food Programme project data, reports from government ministries, and, where such searches failed, newspaper articles and other literature obtained from internet searches. Regression models were then used to analyze the relationships between school feeding costs, the per capita costs of primary education and GDP per capita. RESULTS: School feeding programs in low-income countries exhibit large variations in cost, with concomitant opportunities for cost containment. As countries get richer, however, school feeding costs become a much smaller proportion of the investment in education. The per capita costs of feeding relative to education decline nonlinearly with increasing GDP. CONCLUSIONS: These analyses suggest that the main reason for this decline in the relative cost of school feeding versus primary education is a greatly increased investment per child in primary education as GDP rises, but a fairly flat investment in food. The analyses also show that there appears to be a transitional discontinuity at the interface between the lower- and middle-income countries, which tends to coincide with changes in the capacity of governments to take over the management and funding of programs. Further analysis is required to define these relationships, but an initial conclusion is that supporting countries to maintain an investment in school feeding through this transition may emerge as a key role for development partners. PMID- 22073794 TI - Comparison of median urinary iodine concentration as an indicator of iodine status among pregnant women, school-age children, and nonpregnant women. AB - BACKGROUND: Most surveys that assess the iodine status of populations target school-age children, whereas others may target nonpregnant women with the assumption that the iodine status of these groups is representative of other groups in the same population. OBJECTIVE: To assess whether the median urinary iodine concentration (UIC) of school-age children or nonpregnant women can be used to accurately represent the iodine status of pregnant women. METHODS: Using the World Health Organization Vitamin and Mineral Nutrition Information System and a literature review, we identified urinary iodine surveys that included pregnant women and school-age children and/or nonpregnant women in the same location and year using estimates from the smallest geographic level to increase the number of data points. Linear regression was used to assess the relationships between the median UIC for the comparisons. RESULTS: There were 48 survey pairs with pregnant women and school-age children (total sample sizes of 8,622 and 16,844, respectively), and 26 pairs with pregnant and nonpregnant women (sample sizes of 3,222 and 5,520, respectively). The country contributing the most data points was China. When the median UIC in school-age children or nonpregnant women indicated iodine intake was adequate or above requirements, approximately half the time pregnant women had inadequate iodine intake. CONCLUSIONS: Adequate iodine nutrition status of school-age children or nonpregnant women may not indicate adequate iodine nutrition status among pregnant women. In order to assess the iodine status of pregnant women, the iodine status would need to be assessed in this group. PMID- 22073795 TI - Impact of prophylactic iron supplementation in healthy pregnant women on maternal iron status and birth outcome. AB - BACKGROUND: In spite of the beneficial effect of iron supplementation in iron deficient pregnant women, iron supplementation may not be needed for women who are iron replete or not anemic. Moreover, the theoretical possibility of adverse effects, such as oxidative damage,from administration of iron supplements during pregnancy has been raised. OBJECTIVE: To determine the effect of prophylactic iron supplementation on iron status and birth outcomes among nonanemic pregnant women. METHODS. A randomized, triple-blind clinical trial was conducted. One hundred forty-eight nonanemic pregnant women with hemoglobin > 110 g/L, serum ferritin > 12 microg/L, and gestational age < 20 weeks were randomly assigned to receive either ferrous sulfate (60 mg elemental iron) (n = 70) or placebo (n = 78) until delivery. Hemoglobin concentration and serum ferritin were measured by electronic counter and radioimmunoassay, respectively. Data were analyzed by independent t-tests, ANCOVA, and repeated measures. RESULTS: At delivery, the incidence of iron deficiency was significantly lower in the iron than in the placebo group. There were no significant differences between the two groups in maternal hemoglobin and ferritin concentrations at delivery or in the infant's birthweight, birth length, or length of gestation. CONCLUSIONS: Iron supplementation during pregnancy in nonanemic women with low serum ferritin may have benefits beyond the prevention of iron-deficiency anemia. PMID- 22073796 TI - Dietary patterns and nutritional health of women: the nutrition transition in rural Tanzania. AB - BACKGROUND: Many developing countries are experiencing a rapid nutrition transition in urban areas. OBJECTIVE: To investigate whether a nutrition transition was occurring in a rural area by examining the dietary patterns of women in rural Tanzania. METHODS: A total of 252 women aged 16 to 45 years from three districts of northeastern and central Tanzania participated. During three different seasons in 2006-2007, the women were interviewed with the use of a structured, interviewer-administered questionnaire, including a 24-hour dietary recall. From these recalls, the mean intakes of 12 main food groups were calculated and used to establish five dietary patterns by principal component analysis. Data were also obtained on attitudes toward obesity, body mass index (BMI), hemoglobin level, and measures of socioeconomic status and analyzed for associations with dietary patterns. RESULTS: The five dietary patterns were "traditional-coast," characterized by fruits, nuts, starchy plants, and fish; "traditional-inland," characterized by cereals, oils and fats, and vegetables; "purchase," characterized by bread and cakes (usually fried in oil), sugar, and black tea; "pulses," characterized mainly by pulses, with few or no vegetables; and "animal products," characterized by a high consumption of meat, eggs, and/or milk. Significant positive associations were found, among others, between the purchase pattern and BMI (p = 0.192, p = .005) and between the animal products pattern and wealth (p = 0.168, p = .002). CONCLUSIONS: Differences between traditional and modern nutritional food patterns were evident. This study found the"traditional-inland" pattern to be the most healthy, while the "purchase" food pattern was the most prevalent. The purchase pattern, in particular, may provide some evidence for early stages of the nutrition transition in rural Tanzania. PMID- 22073797 TI - The importance of milk and other animal-source foods for children in low-income countries. AB - BACKGROUND: Milk and other animal-source foods are concentrated dietary sources of macro- and micronutrients. Despite a global increase in milk production and consumption over the past decades, milk and other animal-source foods are often lacking in the diets of children in developing countries. OBJECTIVE: To evaluate the importance of milk and other animal-source food intake in promoting the growth, development, and health of children in low-income countries. METHODS: Original research articles describing observational and intervention studies with unfortified milk, fortified milk, and other animal-source foods in children were identified by searching the PubMed database. RESULTS: Consumption of milk and other animal-source foods by undernourished children improves anthropometric indices and cognitive function and reduces the prevalence of biochemical and functional nutritional deficiencies, reducing morbidity and mortality. Unfortified and fortified milk used in supplementation trials has been well tolerated and widely accepted by parents and children. CONCLUSIONS: To improve the dietary quality of children in low-income countries and further the effort to eradicate extreme poverty and hunger in accordance with the United Nations Millennium Development Goals, additional research is necessary to identify and implement programs and policy supporting increased intake of milk and other animal-source foods. PMID- 22073798 TI - Beyond food insecurity: how context can improve complementary feeding interventions. AB - BACKGROUND: The role of context has not been elaborated with respect to current recommendations for complementary feeding interventions, apart from a gross distinction based on food security. OBJECTIVE: Our objective was to compare two food-insecure settings in sub-Saharan Africa to determine how context (i.e., the set of local social, cultural, and physical circumstances) influences complementary feeding practices and nutrient intakes and how the results can help in the design of a suitable intervention strategy. METHODS: We conducted formative research using 24-hour dietary recalls, household interviews, and focus group discussions with mothers of 6- to 12-month-old infants in rural Zimbabwe (n = 32) and Pemba Island, Zanzibar, Tanzania (n = 44). RESULTS: In both settings, many infants had suboptimal nutrient intakes, poor dietary diversity, and poor hygiene. Breastfeeding practices were poor in Pemba, and the infants' diet had low energy density in Zimbabwe. Beyond food insecurity, contextual determinants of practices included inaccurate indigenous knowledge, time-consuming maternal livelihoods, family eating behaviors, local agriculture, and the local ecosystem. Both settings would require nutrition education, but it should target the broader indigenous ways of learning and family eating behaviors in order to achieve the necessary behavior change. A home-based fortificant would probably be enough for Pemban children, because the ecosystem of the island provides sufficient sources of macronutrients. However, Zimbabwean children appear to need a fortified food based supplement to overcome the poor agricultural and economic context. CONCLUSIONS: Assessing context was essential to intervention design. A framework to guide future formative research is proposed. PMID- 22073799 TI - Assessing the impact of micronutrient intervention programs implemented under special circumstances--meeting report. AB - INTRODUCTION AND OBJECTIVE: The World Food Programme and the Office of the United Nations High Commissioner for Refugees organized a meeting of experts to discuss evaluation of micronutrient interventions under special circumstances, such as emergency and refugee situations. RESULTS: Multimicronutrient interventions for groups with higher needs may include home fortification products for young children or supplements for pregnant and lactating women. The choice of preparation should be guided by target group needs, evidence of efficacy of a product or its compounds, acceptability, and cost-effectiveness. Different designs can be used to assess whether an intervention has the desired impact. First, program implementation and adherence must be ascertained. Then, impact on micronutrient status can be assessed, but design options are often limited by logistic challenges, available budget, security issues, and ethical and practical issues regarding nonintervention or placebo groups. Under these conditions, a plausibility design using pre- and postintervention cross-sectional surveys, a prospective cohort study, or a step-wedge design, which enrolls groups as they start receiving the intervention, should be considered. Post hoc comparison of groups with different adherence levels may also be useful. Hemoglobin is often selected as an impact indicator because it is easily measured and tends to respond to change in micronutrient status, especially iron. However, it is not a very specific indicator of micronutrient status, because it is also influenced by inflammation, parasitic infestation, physiological status (age, pregnancy), altitude, and disorders such as thalassemia and sickle cell disease. CONCLUSION: Given the constraints described above, replicability of impact in different contexts is key to the validation of micronutrient interventions. PMID- 22073800 TI - Effects of multimicronutrient home fortification on anemia and growth in Bhutanese refugee children. AB - BACKGROUND: Anemia remains a significant public health problem in refugee settings. Home fortification with micronutrient powders has been proposed as a feasible option to alleviate micronutrient deficiencies; its efficacy in reducing anemia in children aged 6 to 24 months has been demonstrated in several trials. OBJECTIVE: To evaluate the effectiveness of a large-scale micronutrient powder distribution program in reducing anemia prevalence and promoting growth in refugee children aged 6 to 59 months. METHODS: Four representative cross sectional surveys were conducted 13 months before and 7, 14, and 26 months after initiation of the supplementation program. Data collected on children aged 6 to 59 months included hemoglobin concentration, anthropometric indicators, morbidity, feeding practices, and information on the micronutrient distribution program. The study had a pre-post design with no control group. RESULTS: The overall prevalence of anemia in children did not change significantly between baseline (43.3%) and endpoint (40.2%). The prevalence of moderate anemia decreased over the same period from 18.9% to 14.4% (p < .05). The levels of severe anemia were negligible (< 1%) in all surveys. The prevalence of stunting decreased significantly from 39.2% at baseline to 23.4% at endpoint (p < .001), a relative decrease of40%. Reported coverage, use, and acceptance of micronutrient supplements remained consistently high throughout the study. CONCLUSIONS: In the absence of a control group, changes in key outcomes should be interpreted with caution. The minor effect on hemoglobin status requires further investigation of underlying causes of anemia in this population. The large positive effect on linear growth may be a significant benefit of supplementation if confirmed by future studies. PMID- 22073801 TI - Provision of micronutrient powder in response to the Cyclone Sidr emergency in Bangladesh: cross-sectional assessment at the end of the intervention. AB - BACKGROUND: Micronutrient powder has been endorsed as an effective means to improve the micronutrient status of emergency-affected populations. OBJECTIVE: To document the experience and findings of a cross-sectional assessment of the micronutrient powder program implemented as part of the emergency response to Cyclone Sidr. METHODS: Micronutrient powder was distributed to 100,714 children under 5 years of age and 59,439 pregnant or lactating women severely affected by Cyclone Sidr in Bangladesh. A cross-sectional assessment, including hemoglobin and anthropometric measurements, was conducted after the completion of the micronutrient powder program among children under 5 years of age, lactating mothers, and postmenarcheal adolescent girls in the intervention area. Comparison groups for each, drawn from the control area, which had not received micronutrient powder, were assessed at the same time. RESULTS: The prevalence of anemia among children under 5 years of age was approximately 80% in both areas. Among children in the intervention area, those who consumed at least 75% of the micronutrient powder sachets had a lower prevalence of stunting than those who consumed less than 75% of the sachets (40% vs. 52%, p < .05). Among lactating mothers in the intervention area, the prevalence rates of thinness and anemia were lower among those who consumed at least 75% of the sachets than among those who consumed less than 75% of the sachets (thinness, 31% vs. 46%, p < .05; anemia, 50% vs. 61%, p = .07). For adolescent girls in the intervention and control areas, none of whom had received micronutrient powder, the prevalence rates of anemia were 52% and 45%, respectively (p = .05). CONCLUSIONS: Micronutrient powder may reduce anemia among lactating mothers, when the compliance rate is high. Anemia prevalence prior to micronutrient powder distribution had not been investigated and could have been higher among children and lactating mothers in the intervention than in the control area, resulting in the negation of the potential positive impact of micronutrient powder on anemia. PMID- 22073802 TI - Relationship of the availability of micronutrient powder with iron status and hemoglobin among women and children in the Kakuma Refugee Camp, Kenya. AB - BACKGROUND: Micronutrient powder is a potential strategy to improve iron status and reduce anemia in refugee populations. OBJECTIVE: To evaluate the effect of the availability of home fortification with a micronutrient powder containing 2.5 mg of sodium iron ethylenediaminetetraacetate (NaFeEDTA) on iron status and hemoglobin in women and children in the Kakuma Refugee Camp in northwest Kenya. METHODS: Hemoglobin and soluble transferrin receptor were measured in 410 children 6 to 59 months of age and 458 women of childbearing age at baseline (just before micronutrient powder was distributed, along with the regular food ration) and at midline (6 months) and endline (13 months)follow-up visits. RESULTS: At the baseline, midline, and endline visits, respectively, the mean (+/ SE) hemoglobin concentration in women was 121.4 +/- 0.8, 120.8 +/- 0.9, and 120.6 +/- 1.0 g/L (p = .42); the prevalence of anemia (hemoglobin < 120 g/L) was 42.6%, 41.3%, and 41.7% (p = .92); and the mean soluble transferrin receptor concentration was 24.1 +/- 0.5, 20.7 +/- 0.7, and 20.8 +/- 0.7 nmol/L (p = .0006). In children, the mean hemoglobin concentration was 105.7 +/- 0.6, 109.0 30322 1.5, and 105.5 +/- 0.3 g/L (p = .95), respectively; the prevalence of anemia (hemoglobin < 110 g/L) was 55.5%, 52.3%, and 59.8% (p = .26); and the mean soluble transferrin receptor concentration was 36.1 +/- 0.7, 29.5 +/- 1.9, and 28.4 +/- 3.2 nmol/L (p = .02), in models that were adjusted for age using least squares means regression. CONCLUSIONS: In children and in women of childbearing age, the availability of micronutrient powder was associated with a small improvement in iron status but no significant change in hemoglobin in this refugee camp setting. PMID- 22073803 TI - Understanding low usage of micronutrient powder in the Kakuma Refugee Camp, Kenya: findings from a qualitative study. AB - BACKGROUND: Home fortification with micronutrient powder has been shown to be a low-cost, feasible, and effective approach to address micronutrient deficiencies. A large-scale program distributing micronutrient powder to approximately 50,000 refugees was implemented at the Kakuma Refugee Camp in Kenya. Uptake of the micronutrient powder at distribution points dropped nearly 70%,from 99% to a low of 30%, and remained at 45% to 52% despite increased social marketing efforts. OBJECTIVE: To identify factors at the distal and proximal levels leading to the low uptake of micronutrient powder through a qualitative inquiry. METHODS: In depth interviews were conducted with community leaders, stakeholders, implementing partners, and beneficiaries. Direct observations of food preparation and child feeding were conducted. Focus group discussions were employed to examine perceptions and practices of beneficiaries regarding micronutrient powder use. RESULTS: Superficial formative research and lack of interagency coordination led to insufficient social marketing prior to the program. In addition, community health workers were inadequately trained. This resulted in inadequate communication regarding the health benefits and use of micronutrient powder to the beneficiaries. Reliance on personal experiences with micronutrient powder and issues with its packaging, in part, led to confusion and deleterious rumors, resulting in decreased uptake of micronutrient powder at distribution points. CONCLUSIONS: A successful micronutrient powder program requires careful design, with emphasis on conducting thorough formative research, ensuring the involvement and commitment of all stakeholders from the outset, investigating the role of cultural factors, and ensuring provision of sufficient, adequate, and timely information to the beneficiaries. PMID- 22073804 TI - The universal language of health. PMID- 22073805 TI - Dental Internet marketing: putting the pieces together. PMID- 22073806 TI - Horizontal alveolar ridge augmentation: the importance of space maintenance. AB - At dental implantology's inception, patients seeking tooth or teeth replacement were confronted with the concern of whether they were viable "candidates" for treatment. Largely, this criteria was based on 3-dimensional bone volume present in edentulous sites selected for implant fixture insertion. When surgeons determined this volume as insufficient for implant placement, patients were encouraged to seek alternative restorative therapy. As the ability to regenerate lost tissue, both hard and soft, has evolved, the number of patients now considered "candidates" for implant therapy has increased exponentially. Not only has the ability to regenerate lost hard tissue improved, but it has facilitated prosthetically and mechanically favorable implant positioning. This has led to decreases in mechanical and biologic complications. The efficacy of augmentation techniques has been critically evaluated, and minimizing morbidity while improving outcomes is a goal shared by surgeons and patients alike. This article discusses several methods of hard-tissue augmentation and presents a novel technique of regeneration aimed at improving clinical outcomes while decreasing morbidity associated with older, yet effective modes of ridge augmentation. PMID- 22073807 TI - The clinical significance of keratinized gingiva around dental implants. AB - Whether or not keratinized tissue is needed around dental implants to maintain peri-implant health is a controversial subject. To clarify this issue a search was conducted for clinical trials that appraised the significance ofkeratinized gingiva (KG) around teeth and dental implants. A critical assessment of the data revealed that the literature is replete with studies that contradict one another with respect to the need for KG as it relates to survivability of implants, gingival response to plaque, inflammation, probing depths, recession, and loss of bone. When groups of patients with and without KG were compared with respect to various clinical parameters, a statistically significant better result in the presence of KG could be interpreted to indicate that having KG is advantageous. However, quantitative differences between groups with and without KG were usually very small. Overall, the data was interpreted to indicate that some patients may need augmentation of keratinized tissue to maintain peri-implant health. Ultimately, the decision to augment KG is a judgment call that needs to be made by the treating clinician, because there are not enough data to facilitate development of definitive guidelines relevant to this subject. Apparently, the need for KG is patient specific, and at present there is no method to reliably predict who would benefit from tissue augmentation. PMID- 22073808 TI - Mucogingival considerations following orthodontic therapy: a case report. AB - A healthy periodontium is a prerequisite for any orthodontic intervention to be executed. However, application of orthodontic forces without thoughtful planning can result in not only damage to the attachment apparatus, but also alterations to the associated mucogingival tissues. This article elucidates a case of Miller's Class III gingival recession that developed in relation to the patient's lower right central incisor following orthodontic therapy. Case evaluation pertaining to gingival thickness, the level of underlying alveolar bone, and the inflammatory status of the tissues is critical to avoid the development of such soft-tissue defects. Options for augmentation of such sites prior to application of forces can be explored only if accurate diagnosis and clinical assessment are completed. This concept holds relevance for the treating dentist to identify cases with thin gingival tissue biotype and the propensity for developing dehiscence in order to prevent such mucogingival deformities from becoming established. PMID- 22073809 TI - Implant-assisted overdenture: a case report. AB - A patient's extreme susceptibility to periodontal disease, likely exacerbated by a history of smoking, resulted in severe periodontal breakdown. Employing a systematic approach that identified both patient risk and prognosis using data gathered during the patient examination, a treatment plan was developed that included extraction of structurally compromised teeth and the use of implant assisted complete overdentures. This treatment approach accomplished a reduction of biomechanical, periodontal, and dentofacial risk, as well as an increase in functional harmony. PMID- 22073811 TI - Impression materials. PMID- 22073810 TI - Long-term use of 6.5% hydrogen peroxide bleaching strips on tetracycline stain: a clinical study. AB - This study evaluated the clinical response following extended daily use of a trayless 6.5% hydrogen peroxide (H2O2) tooth bleaching gel in patients with tetracycline stains. MATERIALS AND METHODS: In this clinical trial, participants (N = 30) were assigned to a strip product following screening for tetracycline staining. Subjects used the product for 6 months, with clinical safety and efficacy measurements assessed at the end of each month. The strips were used for 30 minutes twice daily (maxillary arch only). Treatment efficacy was determined by the tooth color change from baseline using an expanded VITA shade guide. Additional shades were added on either side, representing colors whiter than B1 and darker than C4. RESULTS: The strips averaged shade reduction in Months 1, 2, and 3 visits, respectively. Of all the subjects, 65% reached B1 color by Month 6. Treatment was generally well tolerated. Mild and transient tooth sensitivity (46.7%) and oral discomfort (43.3%) were the most common adverse events associated with daily bleaching, yet neither affected study participation. CONCLUSIONS: The 6.5% H2O2 bleaching strip provided significant tooth whitening in subjects with tetracycline stains. CLINICAL SIGNIFICANCE: When used daily for 6 months, a 6.5% H2O2 bleaching strip can be effective in whitening tetracycline stains. The professional strip was well tolerated throughout the 6-month period. This extended use provides additional evidence of clinical safety associated with the use of this product for vital bleaching. PMID- 22073812 TI - Elastomeric impression materials: factors to consider. PMID- 22073814 TI - International stem cell tourism in Russia and India: clinical research, innovative treatment, or unproven hype? PMID- 22073813 TI - Custom shade matching: fine-tuning and patient communication lead to success. AB - Shade matching is a sometimes difficult process that involves a variety of colors and characteristics. Couple this with a patient base that often encompasses a wide range of ages, and final restorations can frequently require adjustment or repair because they have failed to match the patient's natural teeth. In this article the author relates many of his own custom shade-taking experiences in an effort to help dental technicians improve their color-matching strategies and avoid costly mistakes. PMID- 22073815 TI - The fair transaction model of informed consent: an alternative to autonomous authorization. AB - The doctrine of informed consent in bioethics has relied on the view that consent is valid when it represents a patient or research subject's autonomous authorization. In this article we challenge this reigning conception of the validity of informed consent in clinical research, focusing in particular on the problem of the therapeutic misconception. We argue that the autonomous authorization model of informed consent suffers from four defects: (1) it fails to do justice to the relevance of risk-benefit considerations in shaping the criteria for the validity of consent, (2) it compromises the interests of subjects by preventing them from consenting to research participation with less than substantial understanding when doing so would likely be consistent with their preferences and beneficial to them or at least be unlikely to cause them harm, (3) it jeopardizes the interests of investigators by denying them fair notice regarding when the consent of research subjects can be considered valid and thus make it permissible for them to be enrolled in research, and (4) it threatens the reasonable limits on the responsibility of investigators to assure the adequacy of subjects' understanding of what research participation involves. In place of the autonomous authorization model, we present and defend a fair transaction model of informed consent, which better reflects the values served by consent. PMID- 22073816 TI - What it takes to defend deceptive placebo use. AB - A complete defense of deceptive placebo use must address this ethical objection: deceptive placebo use violates patient autonomy, because deceiving a patient about the placebo nature of a proposed treatment prevents her from giving informed consent to the treatment. Unfortunately, this objection isn't always recognized and clearly disambiguated from other ethical concerns. I consider how well several bioethicists who write about placebo use have responded to, or evaded, this objection. I conclude that defenders of deceptive placebo use should, following the lead of Onora O'Neill, argue that deceptive placebo use is compatible with informed consent. PMID- 22073817 TI - Global ethics and principlism. AB - This article examines the special relation between common morality and particular moralities in the four-principles approach and its use for global ethics. It is argued that the special dialectical relation between common morality and particular moralities is the key to bridging the gap between ethical universalism and relativism. The four-principles approach is a good model for a global bioethics by virtue of its ability to mediate successfully between universal demands and cultural diversity. The principle of autonomy (i.e., the idea of individual informed consent), however, does need to be revised so as to make it compatible with alternatives such as family- or community-informed consent. The upshot is that the contribution of the four-principles approach to global ethics lies in the so-called dialectical process and its power to deal with cross cultural issues against the background of universal demands by joining them together. PMID- 22073818 TI - Biodefense research and the U.S. regulatory structure whither nonhuman primate moral standing? AB - Biodefense and emerging infectious disease animal research aims to avoid or ameliorate human disease and suffering arising from the natural outbreak or intentional deployment of some of the world's most dreaded pathogens. Research to develop medical countermeasures to these diseases faces a difficult challenge since the products usually cannot be tested for efficacy in human beings. The U.S. Food and Drug Administration's Animal Rule may be increasingly used to overcome this challenge by allowing researchers to translate animal data into medical countermeasures without human subject efficacy testing. Yet the Animal Rule also has significant implications for increased intensive nonhuman primate research. We argue that despite the common belief that nonhuman primates have a fairly high level of moral standing and the protections for animals that are crucial to the U.S. regulations guiding animal research, the Animal Rule specifically and the regulations generally raise serious problems for the attribution of moral standing to nonhuman primates. We argue, however, that the burden of proof is on a position denying all moral standing to nonhuman primates and compare the implications of the U.S. regulatory structure in this regard with some recent developments in the European Union. PMID- 22073819 TI - Prothrombin fragment 1 + 2 (F1 + 2) in effluent is a useful marker for peritoneal permeability in peritoneal dialysis patients using neutral dialysate. AB - To clarify the influence of neutral dialysate (ND) on peritoneum, we examined changes in peritoneal permeability and in various markers of the coagulation and fibrinolytic system in effluent and the correlations between peritoneal permeability and those markers in peritoneal dialysis (PD) patients using ND. We evaluated 14 patients (8 men, 6 women; mean age: 58.6 +/- 12.0 years) who started PD using ND. The peritoneal equilibration test (PET) was performed to assess dialysate-to-plasma ratio for creatinine (D/P Cr) as peritoneal permeability. Coagulation markers [thrombin-antithrombin complex, fibrin monomer (FM), prothrombin fragment 1+2 (F1 + 2)] and fibrinolytic markers (fibrin degradation products, D-dimer) in effluent were also measured. At 2 years, FM in effluent was significantly lower (p = 0.006). The other markers and the D/P Cr did not change significantly. At the initiation of PD and at 2 years, D/P Cr was significantly correlated with F1 + 2 (r = 0.70 and 0.76 respectively, p < 0.01). Furthermore, multiple regression analysis showed that only F1 + 2 was correlated with D/P Cr at 2 years (r = 0.79, p = 0.004). These results suggest that ND has little influence on coagulation and fibrinolytic markers in effluent. In addition, F1 + 2 is a useful marker for peritoneal permeability in PD patients using ND. PMID- 22073820 TI - What does the dialysate level of matrix metalloproteinase 2 tell us? AB - Long-term peritoneal dialysis leads to encapsulating peritoneal sclerosis (EPS), which is a rare but often fatal complication. The pathogenesis of EPS is characterized by increased inflammation, neoangiogenesis, epithelial-mesenchymal transition (EMT), and fibrosis. Matrix metalloproteinase 2 (MMP-2), which degrades type IV collagen, plays an important role in pathogenesis. Clinical trials report that dialysate levels of MMP-2 can be used as an early marker of peritoneal sclerosis. We aimed to determine the association of MMP-2 with peritoneal function, histology, and effluent cytokine levels in an experimental EPS model in rats. We evaluated data for 71 rats from our various studies using an experimental EPS model. Functional assessment was performed using a 1-hour peritoneal equilibration test with peritoneal dialysis fluid containing 3.86% glucose. Specimens of parietal peritoneum were examined with light microscopy for histologic evaluation. Parietal peritoneum thickness and submesothelial area were measured. Fibrosis, number of vessels, neovascularization, and cellular infiltration were evaluated by one pathologist. The relationships between MMP-2 and other parameters were analyzed using Pearson correlation analysis. Dialysate levels of MMP-2 reflect both functional and histologic change in peritoneum. Levels of MMP-2 were negatively correlated with net ultrafiltration, effluent protein levels, and end (1-hour)-to-initial dialysate concentration ratio of glucose. Cytokines such as vascular endothelial growth factor transforming growth factor beta, monocyte chemotactic protein 1, and osteopontin-which are known to play important roles in neovascularization, inflammation, and EMT leading to fibrosis-were correlated with MMP-2. In peritoneal dialysis patients, MMP-2 levels may be an early marker of EPS and EMT PMID- 22073821 TI - DNA microarray analysis of the epithelial-mesenchymal transition of mesothelial cells in a rat model of peritoneal dialysis. AB - Long-term peritoneal dialysis induces peritoneal hyperpermeability, and the subsequent loss of ultra-filtration causes patients to discontinue peritoneal dialysis. Glucose degradation products (GDPs) in peritoneal dialysis fluids (PDFs) are probably one of the primary causes for peritoneal injury. In the present study, we used a transcriptome analysis to determine the mechanism of peritoneal injury by GDPs. Rats were administered 20 mmol/L methylglyoxal (MGO) in PDF or 20 mmol/L formaldehyde in PDF (100 mL/kg) intraperitoneally for 21 days. The peritoneal membrane in rats that received MGO showed increased thickness and fibrosis. Mesenchymal-like cells over-proliferated on the surface of the peritoneum. A DNA microarray analysis revealed that the expression of 168 genes had increased by more than a factor of 4. The upregulated genes included those that code for extracellular matrix components (such as types III and lV collagen, among others), cell division cycle 42 (Cdc42), an enabled/vasodilator stimulated phosphoprotein-like protein [Ena/VASP (Evl)], and actin-related protein 2/3 complex subunits (Arp2/3). In conclusion, a rat model of peritoneal injury by GDPs induced mesothelial cells to redifferentiate and proliferate, with upregulation of Cdc42, the Evl Ena/VASP, and Arp2/3, suggesting that GDPs induce fibrous thickening of the peritoneal membrane by redifferentiation of mesothelial cells, resulting in hyperpermeability of the peritoneum. PMID- 22073822 TI - Influence of osmotic and oncotic factors on gentamicin and insulin transport across the peritoneal membrane in vitro. AB - Glucose or its polymer is usually added to dialysis solution for the development of sufficient ultrafiltration during peritoneal dialysis. The aim of the present study was to determine the influence of glucose and icodextrin on the transport of gentamicin and insulin from the mesothelial to the interstitial side of the peritoneal membrane. Transfer values are expressed as a coefficient of diffusive permeability, P, in centimeters per second. Each of the molecules was tested in 3 series of experiments using rabbit parietal peritoneum, a modified Ussing chamber, and a mathematical model of mass transport. First, transperitoneal transfers of gentamicin (0.040 g/dL) and insulin (0.1 g/dL) were analyzed in control conditions for 120 minutes. Then, transport parameters for gentamicin and insulin were separately determined before (15-60 minutes) and after (75-120 minutes or 75-130 minutes) the application of glucose (1.8 g/dL) or icodextrin (2 g/ dL) on the mesothelial side of the peritoneal membrane. Insulin transport was observed to be stable in the control series. Gentamicin transfer was not stable; its passage declined by 52% (p < 0.01) in the control series. The mean transfer parameters were 7.41 +/- 1.40 cm/s (x0.0001) over 15-30 minutes and 3.21 +/- 0.54 cm/s (x0.0001) over 75-130 minutes. Gentamicin transfer declined less in the series with glucose or icodextrin, by 21% (p < 0.04) and 30% (p < 0.05) respectively, than in the control series. For insulin, the mean P (+ standard error of the mean) was 0.15 +/- 0.02 cm/s (x0.0001) at the first hour of transfer and 0.14 - 0.02 cm/s (x0.0001) at the second. Glucose induced a nonsignificant intensification of insulin transport. Icodextrin increased insulin passage by 107% (p < 0.03). Osmotic and oncotic factors (glucose and icodextrin) both stabilize the transfer of gentamicin across the peritoneal membrane in vitro. Glucose polymer intensifies insulin transport from the mesothelial to the interstitial side of the peritoneum. Similar modifications might be observed in vivo during peritoneal dialysis or continuous intraperitoneal administration of insulin, influencing the efficiency of those treatments. PMID- 22073823 TI - GDPs and AGEs: impact on cardiovascular toxicity in dialysis patients. AB - Glucose degradation products (GDPs) are highly reactive precursors of advanced glycation end-products (AGEs). High glucose concentrations, GDPs, and AGEs can activate specific pathways, including inflammatory and oxidative stress response pathways, which may adversely affect the cardiovascular system. This review discusses the impact and possible mechanisms of action of GDPs and AGEs with regard to cardiovascular toxicity in chronic kidney disease patients. The AGE RAGE pathway appears to be particularly important in the pathogenesis of cardiovascular diseases in dialysis patients. In the absence of definitive proof from randomized controlled trials, mounting evidence suggests that high levels of GDPs and AGEs play a role in the pathophysiology of cardiotoxicity. PMID- 22073824 TI - Markers of inflammation before and during peritoneal dialysis. AB - In this study, we compared changes in inflammatory markers-C-reactive protein (CRP), pentraxin 3 (PTX3), serum component of amyloid A (SAA), and procalcitonin (PCT)-in 182 subjects: 69 from the general population (GP), 47 with CKD, 19 with an implanted intra-abdominal catheter for peritoneal dialysis ("prePD"), and 47 on peritoneal dialysis (PD). These were the results [median (95% confidence interval)] for the GP CKD, prePD, and PD groups respectively: CRP: 1.40 mg/L (1.15-2.10 mg/L), 5.30 mg/L (3.04-8.06 mg/L), 3.33 mg/L (2.15-12.58 mg/L), 7.25 mg/L (4.43-15.16 mg/L). SAA: 3.10 mg/L (2.90-3.53 mg/L), 7.77 mg/L (4.17-15.83 mg/L), 7.30 mg/L (4.81-10.96 mg/L), 9.14 mg/L (5.31-23.54 mg/L). PCT: 0.028 ng/mL (0.022-0.032 ng/mL), 0.121 ng/mL (0.094-0.166 ng/mL), 0.160 ng/mL (0.090-0.277 ng/mL), 0.363 ng/mL (0.222-0.481 ng/mL). PTX3: 0.54 ng/mL (0.33-0.62 ng/mL), 0.71 ng/ mL (0.32-1.50 ng/mL), 0.56 ng/mL (0.44-1.00 ng/ mL), 1.04 ng/mL (0.65-1.56 ng/mL). After catheter insertion, CRP showed a nonsignificant declining trend that disappeared throughout PD. The behavior of SAA was similar to that of CRP and was not modified by the changes induced by the start of PD. An increase in PTX3 was observed only with PD, which may be related to a local proinflammatory state caused by PD solution. We can conclude that catheter insertion for PD does not account for most of the local inflammatory changes observed in PD patients. PMID- 22073825 TI - Inflammation markers, chronic kidney disease, and renal replacement therapy. AB - Chronic kidney disease (CKD) is associated with a proinflammatory state and an excess of cardiovascular risk. In this work, we describe changes in inflammatory markers-C-reactive protein (CRP), pentraxin 3 (PTX3), serum component of amyloid A (SAA), and procalcitonin (PCT)--in CKD patients compared with a control group of subjects with a normal estimated glomerular filtration rate (eGFR). Blood samples were obtained from 69 healthy individuals (GP) and 70 end-stage CKD patients--25 not yet on dialysis, 22 on peritoneal dialysis (PD), and 23 on hemodialysis (HD). These were the results [median (95% confidence interval)] for the GP CKD, PD, and HD groups respectively: CRP: 1.40 mg/L (1.19-2.11 mg/L), 6.50 mg/L (3.57-8.32mg/L), 7.60 mg/L (2.19-22.10mg/L), 9.60 mg/L (6.62-16.38 mg/L). SAA: 3.10 mg/L (2.90-3.53 mg/L), 7.11 mg/L (3.81-15.40mg/L), 9.69 mg/L (5.07 29.47mg/L), 15.90 mg/L (6.80-37.48 mg/L). PCT: 0.03 ng/mL (0.02-0.03 ng/mL), 0.12 ng/mL (0.09-0.16 ng/mL), 0.32 ng/mL (0.20-0.46 ng/ mL), 0.79 ng/mL (0.45-0.99 ng/mL). PTX3: 0.54 ng/mL (0.33-0.62 ng/mL), 0.71 ng/ mL (0.32-1.50 ng/mL), 1.52 ng/mL (0.65-2.13 ng/mL), 1.67 ng/mL (1.05-2.27 ng/mL). Compared with levels in the GP group, levels of SAA and CRP (systemic response) were significantly higher in CKD patients on and not on dialysis. Levels of PTX3 were higher only in dialyzed patients, significantly so in those on HD (greatly different from the CRP levels). These differing levels might be related to a local reaction caused by an invasive intervention (PD or HD). As eGFR declines and with the start of renal replacement therapy, PCT increases. Levels of PCT could potentially cause confusion when these patients are being evaluated for the presence of infection, and may also demonstrate some microvascular implications of dialysis therapy. PMID- 22073826 TI - Microbiological profile of peritoneal dialysis peritonitis and predictors of hospitalization. AB - Peritonitis, the major complication of peritoneal dialysis (PD), is associated with high morbidity and mortality. It is a major cause of hospitalization and transfer to hemodialysis. In the present study, we aimed to identify predictors of hospitalization in PD-related peritonitis and to examine its microbiology profile over time in our unit to determine the best therapeutic approach. We studied all peritonitis episodes that occurred in a 6-year period (January 1, 2004, to December 31, 2009), evaluating whether adequate treatment could be delivered on an outpatient basis. During the study period, 411 patients were on PD, and 229 peritonitis episodes were recorded in 91 patients. Peritonitis were treated according to unit protocol. The average hospital stay was 11.6 +/- 6.6 days. We observed an increase of Streptococcus (to 19.4% from 7.7%) and a stabilization of coagulase-negative Staphylococcus, S. epidermidis, and S. aureus (from 9.5%, 22.6%, and 3.2% to 7.7%, 30.8%, and 3.8% respectively) peritonitis episodes. The main risk factors for hospitalization were fungal infection, poor 72-hour outcome, inability to perform self-care, and age greater than 80 years. We observed a decline in the incidence of peritonitis, and despite changes in its microbiology profile, no loss of sensitivity to antibiotics used was observed. PMID- 22073827 TI - The utility of prolonged culture of peritoneal dialysis effluent in the diagnosis and management of peritonitis. AB - In this prospective study we examined the effect of prolonging cultures of peritoneal dialysis fluid to 21 days. The extended culture period did not lead to any new or clinically important findings, although late culture findings were obtained in a small number of cases. Prolonged culture of the effluent does not appear to be necessary, although it can lead to extended duration of antibiotic therapy if time on therapy is guided by the first negative effluent culture. PMID- 22073828 TI - Xenophilus aerolatus Peritonitis in a six-year-old boy on maintenance eritoneal dialysis. AB - Peritonitis remains a significant complication of peritoneal dialysis (PD). Although most patients can be treated successfully with antibiotics and continue PD, the poorest outcomes are noted in patients with peritonitis secondary to gram negative organisms, which may lead to temporary or permanent technique failure. Biofilm formation may result in. failure of appropriate antibiotic therapy to eradicate infection, necessitating catheter replacement or a switch to hemodialysis. Here, we report the first case of gram-negative peritonitis caused by Xenophilus aerolatus in a 6-year-old boy on continuous cycling PD. This case highlights the importance of close monitoring of clinical response and of collaboration with the microbiologist and microbiology lab in the identification of unusual organisms, their antimicrobial susceptibilities, and their expected characteristics. PMID- 22073829 TI - Tuberculosis in peritoneal dialysis patients in an endemic region. AB - Tuberculosis has been paid more attention in recent years because of the increase in the number of patients with immune suppression-such as those with renal failure. In the present study, we analyzed patients on peritoneal dialysis (PD) in our city to determine the prevalence and clinical characteristics of tuberculosis in those patients. Patients who had been on a PD program for more than 3 months were reviewed. Demographic characteristics, primary renal disease, comorbidities, and duration of PD were recorded. With regard to tuberculosis, the timing of the diagnosis, any previous history of antituberculosis treatment, family history, site of presentation, drugs used, drug side effects, and disease outcome were recorded. Among 322 patients from 5 PD units who were reviewed, 4 (1.240%) were found to have tuberculosis. Pulmonary involvement was noted in 2 (50%). The diagnosis was made through microbiology in 1 patient, through pathology in 1, and through clinical and radiologic assessment in the remaining 2. Mild transaminitis was recorded in 2 patients as a side effect of treatment. Of the 4 patients, 2 were cured, 1 died, and 1 was taking ongoing treatment. The prevalence of tuberculosis was significantly higher in the study population than in the general population. In a dialysis population, a diagnosis of tuberculosis is often difficult, and extrapulmonary involvement is more common, as observed in our study. The diagnosis of tuberculosis may be made through non-microbiologic approaches, and temporary transaminase elevations may be seen during therapy. PMID- 22073830 TI - Seventeen years' experience of surgical options for encapsulating peritoneal sclerosis. AB - Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term peritoneal dialysis (PD). The mortality rate for EPS has been high, primarily because of complications related to bowel obstruction. However recent advances in clinical research have established the pathogenesis and course of the condition and a treatment strategy. The final therapeutic option for EPS is surgical enterolysis, and we have performed 239 surgical procedures in 181 patients and observed favorable outcomes. Of 181 patients opting for surgery 64 (35.40%) died. Death was related to EPS in 33 patients (18.2%), including 14 who died postoperatively. The overall survival rate at 1, 2, 3, 5, and 8 years after diagnosis was 93%, 83%, 78%, 71%, and 60% respectively. The survival rate for EPS related death at 1, 2, 3, 5, and 8 years after diagnosis was 95%, 90%, 87%, 81%, and 74% respectively. Median survival after diagnosis, considering death from any cause and death from EPS, was 43.9 months and 35.7 months respectively. In conclusion, we present favorable outcomes with EPS surgery in 181 patients encountered over a period of 17years. These data reconfirm that surgical treatment is essential for EPS patients. Encapsulating peritoneal sclerosis may no longer be a fatal complication and can be improved with accurate diagnosis and treatment. PMID- 22073831 TI - Testing a single monthly dose of darbepoetin alpha to maintain hemoglobin levels in continuous ambulatory peritoneal dialysis patients. AB - The newly developed erythropoiesis agent darbepoetin alpha (DA) allows for once monthly dosing in the treatment of anemia in patients on dialysis. This dosing schedule has prompted some studies to examine the efficacy of DA in patients on continuous ambulatory peritoneal dialysis (CAPD). In the present study, we assessed whether intravenous (IV) administration of DA once monthly is effective for maintaining hemoglobin levels near 10.5 g/dL in patients on CAPD. This single center prospective cohort study included 52 clinically stable patients (25 men, 27 women; mean age: 59 +/- 10 years). All patients had been on a stable weekly or twice monthly regimen of recombinant human erythropoietin (rHuEPO) before initiation of the study. To determine the monthly dose of DA, the previously used mean weekly dose of rHuEPO was divided by 200 to determine the equivalent weekly dose of DA in micrograms; that number was then multiplied by 4 to generate the monthly dose requirement. For example, if 3000 IUrHuEPO was being administered weekly, then the monthly dose of DA was calculated to be 60 microg (3000/200 x 4). All patients received a monthly dose of DA the first month, and hemoglobin and other routine laboratory tests were performed monthly for 24 consecutive weeks. In 26 patients, the calculated monthly DA dose remained stable. The monthly dose was increased by 25% in 22 patients and by 50% in 4 patients. With regard to iron stores and iron availability for erythropoiesis, no significant differences were observed in the patients on various doses of DA. Nonsignificant differences in weekly creatinine clearance as determined using the PD Adequest software (Baxter Healthcare, Tokyo, Japan) were observed between the groups. No clinically meaningful differences in other laboratory values between the groups were observed. Once-monthly administration of DA is not always sufficient to maintain hemoglobin levels in patients on CAPD when adequate dialysis therapy is not achieved. PMID- 22073832 TI - Bioimpedance spectroscopy for the detection of hypervolemia in peritoneal dialysis patients. AB - A practical, inexpensive, and reliable method is needed for the assessment of volume status in peritoneal dialysis (PD) patients. In the present study, we investigated the efficiency of bioimpedance spectroscopy (BIS) for detection of hypervolemia. The study enrolled 79 prevalent PD patients (mean age: 47 +/- 14 years; PD duration: 30 +/- 17 months; 55% men; 19% with diabetes) from a single center. Echocardiography and body composition analysis using the BIS technique [50 frequencies (Body Composition Monitor: Fresenius Medical Care, Bad Homburg, Germany)] were performed. Overhydration (OH) and extracellular water (ECW) in liters and OH/ECW ratio were used as volume indices. The mean left ventricular (LV) mass index was 117 +/- 37 g/m2, and 46% of patients had LV hypertrophy (LVH). Mean OH and OH/ECW ratio were 1.3 +/- 1.7 L and 7.6% +/- 9.3% respectively The OH/ ECW ratio correlated with LV mass index (r = 0.237, p < 0.036) and with left atrium index (r = 0.354, p < 0.001). Compared with patients not having LVH, patients with LVH had higher OH values (1.79 +/- 1.82 L vs 0.93 +/- 1.62 L, p = 0.003). In linear regression analysis, the OH/ECW ratio was an independent risk factor for LVH (t = 2.558, p = 0.01). In PD patients, BIS is a reliable method for evaluating volume status. The OH/ECW measured by BIS is a major determinant of LV mass. Control of hypervolemia and blood pressure is associated with better cardiac condition. PMID- 22073833 TI - Clinical presentation in patients more than 80 years of age at the start of peritoneal dialysis. AB - The age of new dialysis patients is rapidly increasing. In the present study, we examined clinical presentation in new peritoneal dialysis (PD) patients 80 years of age or older at our hospital. Data were collected from the records of patients newly starting continuous ambulatory PD (CAPD) therapy between January 2005 and July 2010. During that period, 11 patients 80 years of age or older (average age: 83.1 +/- 3.8 years) were introduced to PD therapy. The reason for dialysis was hypertensive nephrosclerosis in 8 patients, and chronic glomerulonephritis, chronic tubulointerstitial nephritis, and an unknown primary disease in 1 patient each; there were no cases of diabetic nephropathy. At dialysis start, average serum creatinine was 6.1 +/- 1.4 mg/dL, arterial wall calcification was found by computed tomography or chest radiography in 10 of 11 patients (90.9%), and aortic or mitral valve calcification, or both, was found by echocardiography in 3 patients (27.3%). By the end of January 2011, 8 patients had died. Average survival after the start of PD was 31.9 +/- 22.3 months. Hypertensive nephrosclerosis, a cause less often seen in younger patients, was the most common primary disease among our elderly dialysis patients. As we previously reported, vascular and valvular calcification are important factors for determining prognosis; however, no significant relationships were observed in the present study, probably because almost all the patients had such calcifications. PMID- 22073834 TI - Removal of the peritoneal dialysis catheter because of gastrointestinal disease in patients on continuous ambulatory peritoneal dialysis: a single-center case series. AB - We previously reported that peritoneal dialysis (PD)-associated peritonitis is a major cause of PD catheter removal. Another major cause is disease of the gastrointestinal tract, including neoplasm and perforation. In the present study, we reviewed the records of patients who underwent catheter removal at our hospital for reasons other than peritoneal infection--and for gastrointestinal disease in particular. Data were collected from the records of patients who received continuous ambulatory PD (CAPD) therapy between 2004 and 2010 at the Department of Nephrology, Saitama Medical University. Mean duration of CAPD was 6.2 +/- 4.7 years, and mean age at onset was 64.5 +/- 9.6 years. During the investigation period, catheters were removed from 13 patients (4 men, 9 women) because of gastrointestinal disease: gastric cancer in 3 cases, colon cancer in 3 cases, perforation of the lower gastrointestinal tract in 3 cases, and other reasons in 4 cases. Examination of pathology specimens obtained from 6 patients including 1 in whom contrast-enhanced computed tomography indicated the presence of encapsulating peritoneal sclerosis (EPS)-revealed mild fibrosis in the subserous layer. No patient died of infection after a surgical procedure. Moreover, throughout the observation period, no patient developed new EPS or postoperative ileus. The present study suggests that CAPD itself seems to be free of untoward effects during the postoperative course in these patients. PMID- 22073835 TI - Update on cardiorenal Syndrome: a clinical conundrum. AB - Our understanding of the cardiorenal syndrome continues to progress. Decades of research have led to a better definition of the clinical cardiorenal syndrome and have laid the groundwork for understanding its pathophysiology. Although improvements have been made, there are still knowledge gaps concerning the interactions of these two organ systems. In the present review, we examine those interactions in the setting of acute and chronic cardiac decompensation and the resulting impacts on renal dysfunction. Recognition and prevention of this syndrome may help to better serve a growing patient population. PMID- 22073836 TI - Chronic abdominal pain in a patient on maintenance peritoneal dialysis. AB - Encapsulating peritoneal sclerosis (EPS) is an uncommon but one of the most serious complications in patients on long-term peritoneal dialysis (PD). The diffuse thickening and sclerosis of the peritoneal membrane that characterizes EPS leads to decreased ultrafiltration and ultimately to bowel obstruction. Given that the prognosis of established EPS is poor, early recognition of the preceding symptoms is essential. Computed tomography of the abdomen is a reliable and noninvasive diagnostic tool. Typical computed tomography features of EPS include peritoneal calcification, bowel wall thickening, peritoneal thickening, loculated fluid collections, and tethered bowel loops. These findings are diagnostic of EPS in the appropriate clinical setting. Here we present a case report of chronic abdominal pain in a patient on maintenance PD representing a case of EPS. PMID- 22073837 TI - Personalization of automated peritoneal dialysis treatment using a computer modeling system. AB - The use of almost standardized dialysis programs--and the absence of any adjustment over time in these program to match the progressive decline in residual kidney function, in addition to the reduction in peritoneal depuration because of the frequency of peritonitis and the use of solutions containing high glucose concentrations--often leads to technique drop-out and transfer to hemodialysis. Our study enrolled 15 clinically stable patients (13 white men, 2 white women; average age: 67.3 +/- 12.99 years; average dialysis vintage: 32.25 +/- 25.10 months) who had been on automated peritoneal dialysis treatment with a standard treatment profile for at least 6 months (dwell time per cycle and solutions fixed at various glucose concentrations in all exchanges). After a peritoneal equilibration test had been performed and clearances (peritoneal and renal) were measured, the dialysis program was modified, individualizing it to the patient ' peritoneal membrane transport by the Twardowski system of classification and taking into account the patient's residual diuresis and need for ultrafiltration. The change was implemented using the Patient on Line software created by Fresenius Medical Care (Bad Homburg, Germany). After a month of personalized dialysis treatment, weekly peritoneal Kt/V in the study group increased significantly (to 1.47 + 0.61 from 1.02 +/- 0.37, p = 0.001); no difference in renal Kt/V was observed. Total Kt/V reached levels of optimum dialysis adequacy (to 2.21 +/- 0.28 from 1.62 +/- 0.33, p = 0.0001). Weekly peritoneal creatinine clearance also increased to 32.86 +/- 16.94 L/1.73 m2 from 22.27 +/- 9.16 L/1.73 m2 (p = 0.005), with renal creatinine clearance essentially stable, and total weekly clearance increasing to 67.58 +/- 14.52 L/1.73 m2 from 53.51 +/- 16.86 L/1.73 m2 (p < 0.0001). The dialysis adequacy improvements obtained involved no statistically significant differences in the total infused volume of dialysis solution, ultrafiltration, or the duration of dialysis treatment. It should also be noted that no changes in residual diuresis occurred. PMID- 22073838 TI - The importance of the Patient's training in chronic peritoneal dialysis and peritonitis. AB - In a chronic disease, traineeship in the methodology to be used to treat oneself is a key part of success from the beginning and during long-term treatment. In chronic peritoneal dialysis (PD), peritonitis emphasizes, in a certain way, the result of the apprenticeship. We set out to evaluate the relationship between the number of PD training lessons and the frequency of peritonitis. According to the number of lessons, we established three groups: A, up to 8 lessons; B, 9-13 lessons; and C, 14 or more lessons. We evaluated peritonitis rates and micro organisms, and for the three groups, we compared (Kaplan-Meier method) peritonitis-free survival (PFS) at 1 year of treatment, with significance set at (log rank) p < 0.05. The study enrolled 90 patients (mean age: 51.5 +/- 15.33 years; 37 men). Respectively, groups A, B, and C included 27, 46, and 17 patients with an at-risk duration of 1535, 2879, and 665 patient-months (mean: 56.9 +/- 44, 62.6 +/- 47, and 39.1 +/- 37.8 patient--months), of whom 35%, 37%, and 24% experienced no peritonitis, for peritonitis rates of 0.31, 0.37, and 0.47, with coagulase-negative Staphylococcus (CNS) peritonitis rates of 0.125, 0.12, and 0.235, and PFS rates of 76.9%, 80.4%, and 70.6%. The PFS was not significantly different between the groups (p > 0.05). During 1 year of treatment, all three groups experienced a satisfactory PFS. More frequent retraining should be considered in patients who needed more training lessons at the start of PD. PMID- 22073839 TI - Gynecologic issues in peritoneal dialysis. AB - This paper reviews the issues associated with the reproductive system in the special population of female patients with end-stage renal disease on peritoneal dialysis (PD). We summarize current knowledge concerning cancer screening tests, elective and urgent gynecologic procedures, and the issues of menstruation, contraception, pregnancy, and delivery in these patients. Finally, we present the potential effects of gynecologic problems on PD and the complications of PD that can present with symptoms of the female genitalia. PMID- 22073840 TI - Network 13 partnership to improve the influenza, pneumococcal pneumonia, and hepatitis B vaccination rates among dialysis patients. AB - Vaccinations are available for primary prevention of many infections in adults. Morbidity and mortality from invasive diseases such as influenza and Streptococcus pneumoniae (pneumococcus) remain high and may be largely preventable by vaccination of high-risk adults, including dialysis patients. The current 23-valent vaccine-efficacious, with a low adverse event profile-is widely available. Revaccination is also recommended in patients with immunocompromising conditions, including chronic kidney disease. Despite having many opportunities to be vaccinated, adult hemodialysis and peritoneal dialysis patients are often missed During the recent H1N1 influenza outbreak, we conducted a performance improvement project to increase the vaccination rates for pneumococcal pneumonia, hepatitis B, and influenza, with a special focus on prevention. The project included an education phase, baseline assessment of vaccination rates, intervention, and a follow-up assessment of vaccination rates. The geographic jurisdiction of ESRD Network 13 encompasses the states of Arkansas, Louisiana, and Oklahoma. At the beginning of the network-wide project, the documented state specific rates for influenza immunization were below the average influenza immunization rates for adults reported by Centers for Disease Control and Prevention and far below its target for adults. Our improvement project incorporated educational interventions to improve patient acceptance of vaccinations, educational interventions to improve staff participation in quality improvement activities, and improved techniques of quality improvement data collection and analysis by participants. During this project, the immunization rates for hepatitis B and pneumococcal pneumonia were also reviewed. At project's conclusion, improvement was demonstrated in all three focus areas, with statistically significant improvements noted in both influenza and pneumococcus vaccination rates. The use of educational interventions to improve staff participation in quality improvement, and the collection and analysis of quality improvement data can be replicated in many practice settings to improve immunization rates for dialysis patients and other patients with chronic illnesses. PMID- 22073841 TI - Preservation of residual renal function in dialysis patients. AB - The number of patients with end-stage renal disease continues to increase worldwide, but the 5-year survival probability for patients on dialysis remains low. Preservation of residual renal function (RRF) is widely recognized to be important in the pre-dialysis setting, but now, its benefit for health and quality of life in people on dialysis has been well established. Preservation of RRF has consistently been shown to improve circulating levels of inflammatory markers, middle molecule clearance, blood pressure, and other markers of dialysis adequacy. Residual renal function has also been associated with improved survival on dialysis. This article reviews strategies for preserving RRF in patients on dialysis to improve long-term survival in this population. PMID- 22073842 TI - Different prescribed doses of high-volume peritoneal dialysis and outcome of patients with acute kidney injury. AB - The optimal dialysis dose for the treatment of acute kidney injury (AKI) is controversial. No studies have directly examined the effects of peritoneal dialysis (PD) dose on outcomes in AKI. From January 2005 to January 2007, we randomly assigned critically ill patients with AKI to receive higher- or lower intensity PD therapy (prescribed Kt/Vof 0.8 and 0.5 per session respectively). The main outcome measure was death within 30 days. Of the 61 enrolled patients, 30 were randomly assigned to higher-intensity therapy, and 31, to a lower intensity PD dose. The two study groups had similar baseline characteristics and received treatment for 6.1 days and 5.7 days respectively (p = 0.42). At 30 days after randomization, 17 deaths had occurred in the higher-intensity group (55%), and 16 deaths, in the lower-intensity group (53%, p = 0.83). There was a significant difference between the groups in the PD dose prescribed compared with the dose delivered (higher-intensity group: 0.8 vs. 0.59, p = 0.04; lower intensity group: 0.5 vs. 0.49, p = 0.89). The groups had similar metabolic control after 4 PD sessions (blood urea nitrogen: 69.3 +/- 14.4 mg/dL and 60.3 +/ 11.1 mg/dL respectively, p = 0. 71). In critically ill patients with AKI, an intensive PD dose did not lower the mortality or improve the recovery of kidney function or metabolic control. The PD dose is limited by dialysate flow and membrane permeability, and clearance per exchange can decrease if a shorter dwell time is applied. PMID- 22073843 TI - Subacute polyneuropathy in a patient undergoing peritoneal dialysis: clinical features and new pathophysiologic insights. AB - Recently, demyelinating polyneuropathies have been reported in end-stage renal disease patients. These acute and subacute neuropathies share a demyelinating feature and may develop after the initiation of continuous ambulatory peritoneal dialysis. The pathogenesis of these non-chronic forms of neuropathy remains unclear. We report a case of subacute polyneuropathy that posed a clinical dilemma. PMID- 22073844 TI - Effects of oral paricalcitol on hyperparathyroidism and proteinuria in peritoneal dialysis patients. AB - Severe secondary hyperparathyroidism is a complication of chronic kidney disease. Paricalcitol is a vitamin D receptor activator with efficacy in the treatment of hyperparathyroidism that also has the minor side effects of hypercalcemia and hyperphosphatemia. As a pleiotropic effect, paricalcitol reduces proteinuria in patients with chronic kidney disease stages 2-4. Oral paricalcitol offers an alternative way to treat hyperparathyroidism and proteinuria in peritoneal dialysis patients. Our prospective study enrolled 18 patients with hyperparathyroidism (6 with diabetes also) who were given oral paricalcitol at initial dose of 1-2 microg daily, depending on their level of intact parathyroid hormone (iPTH). In the 1st month, iPTH levels declinedsignificantly to 295 +/- 147 pg/mL from 670 +/- 318 pg/mL, and by the 3rd month, they declined to 192 +/- 340 pg/mL (p < 0.001). Without modifications to doses of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker, proteinuria declined in the 1st month to 1.41 +/- 1.5 g/L from 1.68 +/- 1.7 (p = 0.006) and, in the 3rd month, without statistical significance. In some patients, the dose of paricalcitol was reduced because of iPTH levels that were too low at 1 month. The patients whose doses of paricalcitol were maintained at 3 months showed a reduction in proteinuria to 2.1 +/- 2.1 g/L daily from 3.1 +/- 2. 7 g/L (p = 0.04) and to 2.3 +/- 2.1 g/day from 5.0 +/- 6.1 g/day (p = 0.012). In conclusion, paricalcitol is effective for treating hyperparathyroidism in patients on peritoneal dialysis and seems also to have an antiproteinuric effect in these patients. PMID- 22073845 TI - Does cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism, improve arterial stiffness in patients on continuous ambulatory peritoneal dialysis? AB - Vascular calcification (VC) and arterial stiffness (AS) are major contributors to cardiovascular disease, and in chronic kidney disease, VC and AS are correlated. Disorders of calcium and phosphate metabolism contribute to the progression of VC and to increases in AS. The efficacy of cinacalcet (CIN) in reducing AS in patients on continuous ambulatory peritoneal dialysis (CAPD) has not been determined. The present study enrolled 19 CAPD patients (12 women, 7 men; mean age: 62.2 +/- 3.6 years) with serum intact parathyroid hormone (iPTH) greater than 500 ng/dL (mean value: 675 +/- 106 ng/dL) in whom daily oral treatment with CIN 25 mg was started. If administration of CIN for 3 months failed to reduce the level of iPTH to less than 300 ng/dL, the dose of CIN was increased to 50 mg daily. Before the start of CIN and at 3 years after the start of CIN, pulse wave velocity (PWV) was determined. In 11 patients, levels of iPTH were reduced to less than 300 ng/dL; levels in the rest of the patients remained high. We observed no significant differences in PWV before CIN and at 3 years after CIN start (1856 +/- 198 cm/s vs. 1726 +/- 187 cm/s). Multivariate regression analysis of PWV demonstrated that both systolic blood pressure and changes in serum levels of phosphate contributed to decreases in PWV In patients receiving CAPD, VC and AS might be the result of higher systolic blood pressure and increased serum levels of phosphate. PMID- 22073846 TI - Bone mineral density, its predictors, and outcomes in peritoneal dialysis patients. AB - The objective of the present work was to assess bone mineral density (BMD) and its predictors in peritoneal dialysis (PD) patients, to check the history of those patients 4 years after the assessment, and to relate thoses outcome to BMD. We used dual-energy X-ray absorptiometry to measure BMD in 26 patients at the femoral neck (FN), and we related those measurements to demographic, nutrition, and laboratory data. Four years after the assessments, the outcomes of those patients were checked and related to BMD. In the study patients, the mean FN BMD was 0.842 +/- 0.137 g/cm2. Serum albumin, lean body mass, alkaline phosphatase (ALP), and treatment with acetylsalicylic acid were significant predictors for BMD in the first multivariate model. A second model included blood pH, serum phosphorus, serum creatinine, and age as significant BMD predictors. Hemoglobin or hematocrit could have replaced phosphorus as a BMD predictor The prevalences of abnormal values for BMD predictors in the study patients were phosphorus > 4.5 mg/dL, 69.2%; pH < 7.36, 53.8%; albumin < 3.5 g/dL, 46.1%; ALP > 104 IU/L, 23.1%; and hemoglobin < 11.0 g/ dL, 23.1%. In 8 patients, a successful renal transplantation occurred at 8.5 +/- 9.3 months; 9 patients died at 25.9 +/- 12.5 months; and 9 patients continued dialysis for a further 50.4 +/- 1.7 months. The highest BMD was found in the patients who underwent renal transplantation (0.962 +/- 0.110 g/cm2); the lowest BMD was found in the patients who died (0.737 +/- 0.100 g/ cm2, p = 0.001). In PD patients, low BMD indicates worse outcome. High prevalences of predictors for low BMD (age, poor nutrition status, metabolic acidosis, high phosphorus, anemia) also contribute to worse outcome in PD patients. PMID- 22073847 TI - Acute graft versus host disease in hematopoietic stem cell alotransplant recipients. AB - INTRODUCTION: The transplantation of hematopoietic stem cells (HSCT) is a therapeutic intervention where the hematopoietic stem cells and the cells originating from them are being removed and replaced by the normal stem cells of donor or the patient him/her-self. HSCT today represent standardized biological manipulation for treating malignant, genetic and autoimmune diseases. The application of allogeneic hematopoietic stem cell transplantation (HSCT) is limited by life-threatening complications such as severe or acute graft-versus host disease (GVHD). Despite intensive prophylaxis with immunosuppressive agents, the incidence of GVHD occurs in 9-50% of patients undergoing transplant with an identical HLA sibling matched donor and 75% of patients undergoing unrelated HLA donors. AIM OF STUDY: To evaluate our experiences in GVHD prophylaxis and treatment after alloHSCT, GVHD incidence and prognostic factors and administration of new immunosuppressive regiments. Can we recognize clinical parameters which are associated with occurrence and severity of graft-versus-host disease? PATIENTS AND METHODS: Starting from September 2000 till September 2010, 63 patients (36 males and 27 females) at the age of 16-56 (median range 33 years) with hematological malignancies were treated with alloHSCT on Department of Hematology, Clinical Centre, Skopje. In 10 patients bone marrow was used as source of stem cells and in 53 patients stem cells were obtained from peripheral blood. From the group of 63 patients, 26 patients had active disease at the time of transplantation. GVHD prophylaxis was accomplished with combination of cyclosporine and methotrexate (Seattle regimen) or more intensive immunosuppression regiments. RESULTS: GVHD was noticed in 30 patients (47.6%) and in 33 patients (52.4%) a manifestation of GVHD was noticed. Acute GVHD was noticed in 24 patients (38%) and chronic GVHD in 20 patients (31.7%) The remaining 32 patients (45%) achieved complete clinical and hematological remission. Lethal outcome was confirmed in 31(49%) patients (9 from chrGVHD, 6 from acute GVHD, 16 from disease relapse). CONCLUSION: The incidence of acute GVHD in our study was 38% and 31% for chronic GVHD. The most common GVHD reaction was registered in female donors and male recipients, with higher GVHD incidence in elderly patients. In all patients stem cells were obtained from peripheral blood. Active disease, sex, source of hematopoietic cells, age and conditional regiments are the most significant predictive factors with the high incidence of GVHD. PMID- 22073848 TI - Chronic airflow obstruction syndrome due to pulmonary tuberculosis treated with directly observed therapy--a serious changes in lung function. AB - The origin of Chronic airflow obstruction (CAO) syndrome in active Tuberculosis (TB), despite significant similarities with chronic obstructive pulmonary disease (COPD), still remains unknown. The aim of the study was to examine the potential causes and risks for the development of CAO syndrome in new cases of pulmonary TB. DESIGN: Prospective, nest case-control study. PATIENTS: 40 patients with newly detected cavitary pulmonary TB and initial normal respiratory function, diagnosed and treated according to DOTS strategy. MEASUREMENTS AND RESULTS: The average values of Snider's radiological score during TB treatment were significantly reduced (p < 0.001), as well as average values of non-specific systemic serum markers of inflammation. The average values of FEV1 (%), both before, during and at the end of completion of TB treatment were significantly decreased (p < 0.05;). Linear regression analysis confirmed a statistically significant association between changes in the values of FEV1 (%), resulting in TB treatment completion, and the value of Snider's radiological score and the sputum culture conversion rate. From the initial findings of normal pulmonary ventilation tests, upon the completion of TB treatment 35.0% of observed patients developed the CAO syndrome. Logistic regression analysis confirmed a positive familiar burden for COPD, Snider's radiological score at the beginning of TB treatment and sputum conversion rate on culture, as statistically significant predictors, while multivariate logistic regression analysis confirmed Snider's radiological score at the beginning of TB treatment and sputum conversion rate on culture as most significant risk factors for CAO syndrome occurrence and development. CONCLUSION: The CAO syndrome is often a consequence and significant functional impairment of the respiratory system, during the reparative processes in active TB, even in the absence of risk factors for COPD. Only microbiological cure of TB patients with underlying risks for disorders of lung function, is not sufficient and effective approach for prevention of their further potential health deterioration. PMID- 22073849 TI - What happens with airway resistance (RAW) in asthma and COPD exacerbation. AB - BACKGROUND: To show that during the exarcerbration of asthma and COPD, increased airway resistance is accompanied with decreased spirometry values (FVC, FEV1, FEF50, and PEF) also comes increasing of airway resistance (RAW). PATIENTS AND METHODS: This research included 74 patients, in exacerbation phase of disease. All the patients got spirometry and plethysmography measurements, including adequate therapy, and after at least one month on control examination they repeated spirometry and plethysmography and answered a short life questionnaire. RESULTS: The mean value of RAW after therapy in asthma is decreased for -17.68% and in COPD for -15.44%. The mean value of RAW in all levels of obstruction is higher in COPD than in asthma, before and after therapy. After therapy spirometry values (FVC, FEV1, FEF50, and PEF) were significantly increased in asthma than in COPD. From questionnaire analyses 78.37% (58) of patients felt well, 17.57% (13) felt the same like before therapy and 4.05% (3) of them felt worst. All the patients who felt worst were in COPD group of patients. All of them had increased RAW, almost all felt better (96.43%) had decreased RAW. In asthma nobody felt worst. In most of the patients (76.67%) who felt better RAW was decreased. CONCLUSION: Adequate therapy during exacerbation of asthma and COPD decreases value of RAW and increases spirometry values. Increase in spirometry values in asthma is much higher than in COPD. Mean values of resistance in COPD are higher before and after therapy than in asthma. There is a negative relationship between subjective experience of illness and the level of resistance. Measuring of RAW can be a good parameter for monitoring COPD and asthma control. PMID- 22073850 TI - The evaluation of impact of BPH surgical treatment with the open prostatectomy and transurethral resection of the prostate methods on the quality of life. AB - INTRODUCTION/OBJECTIVE: Benign prostatic hyperplasia is one of the most common diseases in older men. The objective of this study was to evaluate the impact of the surgical treatment of the benign prostatic hyperplasia (BPH) with the methods of open prostatectomy (OP) and transurethral resection of the prostate (TURP) on the quality of life. METHODS: The research material was based on 80 patients, out of whom 40 patients were treated with the method of open prostatectomy (Group A), and the other 40 patients with the method of transurethral resection of prostate gland (Group B) due to benign prostatic hyperplasia. All patients were under the age of 80 years old (approximate age in Group A 70.23 with variation interval of 21 years old, and in Group B 69.37 with variation interval of 22 years old), with the International Prostate Symptom Score (IPSS) value >19 points, postvoid residual urine higher than 150 ml, the weight of benign prostatic gland hyperplasia tissue over 30 grams for method of prostate transurethral resection, and over 80 grams for the method of open prostatectomy. The quantification of the quality of life, as a consequence of urinary symptoms, was done by the Quality of Life Index (QLI) which is question No 8 in IPSS. All patients were determined the value of this score before the operation, and then in postoperative period in time intervals of 4.8 and 12 weeks. RESULTS: The QLI arithmetic mean, before the operation, was 5.55 points in Group A, and 5.45 points in Group B. During postoperative checkups in time intervals of 4.8 and 12 weeks, the arithmetic means in Group A were 0.975, 0.450 and 0.100 points, and in Group B 1.850, 1.700 and 1.575 points. By analyzing the obtained results, there was a highly statistically significant difference between preoperative test results and the results during all the postoperative checkups in both groups, A and B. By testing the difference of the QLI arithmetic mean between the patients in both groups, preoperatively there was no statistically significant difference, but during all postoperative checkups, there was a highly statistically significant difference between the test values. CONCLUSION: The surgical treatment of BPH leads to significant improvement of the quality of life, as a consequence of urinary symptoms. The improvement of the quality of life was more evident in patients whose BPH was treated with the OP method. PMID- 22073851 TI - Selection of treatment method for pelvic ring fractures. AB - INTRODUCTION: The pelvis is the central part of the body that receives the weight from the vertebral column and transfers it to the lower extremities. It protects the internal organs with its specific structure and shape. OBJECTIVE: The study aims to compare the clinical outcomes of emergency non-surgical and surgical treatment of such patients, to analyze the types and severity of complications and final functional outcome. MATERIAL AND METHODS: We present a series of 47 patients treated in the period between 1999 and 2009 at the Traumatology Clinic, CHC Banja Luka. According to Marvin Tile's classification, fractures were distributed as follows: Type A fractures occurred in 19 patients (40.6%), Type B in 18 (38.1%) and Type C in 10 (21.3%). 30 patients (63.8%) were polytraumatised, with craniocerebral injuries in 12 patients (25.5%), chest cavity injuries in 5 (10.6%) and abdominal organ injuries in 13 patients (27.6%). 27 patients (57.4%) had clinical and laboratory signs of hemorrhagic shock on admission, while 26 patients (56.2%) received conservative treatment and 21 patients (43.8%) were treated using surgical methods of stabilization of the pelvic ring. RESULTS: The analysis of the outcomes of treating pelvic ring fractures in our series of patients by using radiography (x-rays according to Slatis) showed that out of 47 treated patients, the outcomes were excellent in 28 (60%), good in 7 (15%), fair in 5 (12%) and poor in 7 (14%). The functional outcomes in all patients were evaluated according to the D'Aubigne-Postel scale, on average 18 months after the trauma. The outcomes were excellent in 22 patients (45%), good in 15 (31%), fair in 4 (9%) and poor in 6 (14%). The chi-square test showed that there was no significant statistical difference between the outcomes monitored using x-rays and functional outcomes monitored using the D'Aubigne-Postel scale (p = 0.097). The surgical treatment efficiency coefficient was introduced for the purpose of comparative evaluation of treatment outcomes. The surgical treatment efficiency coefficient, compared with conservative treatment, showed that all evaluated parameters were between 1.56 and 16.33 times lower in surgical treatment, which represents the more favorable outcome. CONCLUSION: We can conclude that conservative treatment is the treatment of choice for Tile's Type A fractures, external fixator for treating Type B fractures (including all subtypes), and internal fixation, as mono therapy or in combination with external fixator, for treating Type C2 and Type C3 fractures. Surgical treatment, compared with conservative treatment, allows faster mobilisation of the patient and it shortens the recovery period, which in turn lowers the total treatment costs. PMID- 22073852 TI - Aphasia disorders outcome after stroke. AB - INTRODUCTION: Aphasia is considered to be the most difficult disorders of speech language communication, and is often companion by all forms of cerebrovascular disease. GOAL: To determine the outcome of aphasia disorder a year after a stroke and stroke type influence on the outcome of aphasia disorders. MATERIAL AND METHODS: We analyzed one-year outcome of aphasia disorders in patients who had a first stroke. Patients were tested by a speech pathologist with the International test for aphasia, immediately after admission and one year after the stroke. All patients that were hospitalized during treatment had a speech therapy and only a small number of patients were realsed from hospital. RESULTS: Out of 74 patients with aphasia who were discharged from hospital within one year 20 patients died and 2 patients did not respond to control clinical treatment review. Analysis of the remaining 52 respondents determined that out of the 10 patients with global aphasia 8 (80%) evolved into another aphasia syndrome, and two (20%) remained unchanged in form. In most cases, global aphasia was transformed in mixed non fluent aphasia (4 of 10 patients or 40%), and in two cases (20%) global aphasia was transformed in Broca aphasia. Broca aphasia (n = 20) in other forms evolved in 9 patients (45%), and 11 patients (55%) remained unchanged in form. Anomic aphasia had 11 patients (78.6%) which remained unchanged in form, while 3 (21.4%) evolved into an Alexia agraphia. Full recovery was noted in two patients (3.84%). Type of stroke did not affect the outcome of aphasia disorders. Out of the 52 analyzed patients after hospitalization, unfortunately, only 11 (21.2%) had some kind of speech pathology treatment after leaving the hospital. CONCLUSION: One year after the stroke severe aphasia evolved into a lighter form in a significant number of patients. Most often anomic aphasia remained (34.6%), followed by Broca (25%) and Conductive aphasia (7.7%). Type of stroke does not affect the outcome of aphasia disorders. Unfortunately only a small number of patients (21.2%) continued with aphasia speech therapy after leaving the hospital. PMID- 22073853 TI - The role of echocardiography in diagnosis and follow up of patients with takotsubo cardiomyopathy or acute ballooning syndrome. AB - BACKGROUND: The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy was first described in Japan approximately 20 years ago (Satoh and coworkers, 1991). It was later described elsewhere as well and is being increasingly recognized. Takotsubo Cardiomyopathy characterized by transient apical and midventricular LV dysfunction in the absence of significant coronary artery disease that is triggered by emotional or physical stress. Its name refers to a contraption used for catching octopuses and suggests the aspect assumed by the ventricle during the systole due to the typical regional wall motion abnormalities that occur after onset. Takotsubo cardiomiopathy occurring mainly in post-menopausal women, echocardiography in the Takotsubo cardiomyopathy reveals during its acute phase a ballooning resembling the octopus trap configuration--the apex and lateral ventricular segments are hypokinetic while the base is hyperkinetic--along with reduced ejection fraction. Ventricular function will usually recover within a few days/weeks. OBJECTIVE AND PURPOSE: The objective of this study is to determine the role of echocardiography in detecting and establishing the diagnosis of Takotsubo cardiomiopathy in patients with suspect acute coronary syndrome and during the follow up period. PATIENTS AND METHODS: The study covered 12 adult patients the majority are women (92%) who were subjected to echocardiography evaluation as part of the clinical cardiological examination due to suspect acute coronary syndrome or Takotsubo Stress Cardiomyopathy. The patients were examined on an ultrasound machine Philips iE 33 x Matrix, ATL HDI and GE Vived 7 equipped with all cardiologic probes for adults and multi-plan TEE probes. We evaluated clinical characteristics, LV systolic function, biomarkers, and prognosis in all patients. RESULTS: Among all the patients referred for Echocardiographic evaluation for left ventricle motion abnormalities with suspect acute coronary syndrome, the echo exam revealed 12 patients with acute apical ballooning which involving the left ventricular apex and med-ventricle. The triggering factors were physical stress in 4 patients (33%) and emotional stress in 8 patients (67%). The initial symptom was chest pain (n = 8, 67%) rather than dyspnea (n = 4, 33%). An initial electrocardiogram (EKG) presented ST-elevation (n = 10, 83%) and T-wave inversion (n = 2, 17%), other data are shown on Table 2. Among the all patients 8 of them (66%) had normal EF by the 1st follow up (47 +/- 51 days), and the rest 4 patients (34%) had normal EF by 68 +/- 96 days. CONCLUSION: Widespread uses of echocardiography has contributed to more frequent recognition of Takotsubo stress cardiomyopathy and highlight the central role of this noninvasive method from an echocardiographers' perspective. PMID- 22073854 TI - Quality of life in patients suffering from Parkinson's disease and multiple sclerosis. AB - INTRODUCTION: Multiple sclerosis (MS) and Parkinson's disease (PD) are chronic diseases with unpredictable course causing progressive physical disability and cognitive decline, and broadly affecting the patient's life, social interaction, recreational activities and overall life satisfaction. GOALS: To examine the quality of life of patients with PD and MS, and investigate the existence of differences between the degree of impairment to the quality of life in PD and MS. METHODS: A prospective study was conducted at the Neurology Clinic, University Clinical Center in Tuzla in the period from December 2005 until May 2007. The study included subjects with confirmed diagnosis of MS and PD. We analyzed 50 patients with PD and 50 patients with MS, with disease duration 1-5 years without any or with mild cognitive impairment. Quality of life was assessed using the SF 36 scale comprised of 36 questions in eight health profiles. RESULTS: There was no significant difference in gender frequency in our study sample of patients with PD, while in MS group of patients there were a significantly more females. The average age of the PD patients was 63.18 +/- 10.42, and in patients with MS 37.4 +/- 8.65 years. In our study the relative influence of PD and MS on quality of life was similar after controlling the duration of the disease, and there were some differences in relation to the degree for clinical disability. Subjects showed reduced QoL independently of the duration of illness (patients with PD in 88% of cases, and multiple sclerosis in 84% of cases). There are significant differences in the occurrence of poor quality of life in patients with PD were in advanced clinical stages of disease for the physical, mental dimension of the SF 36 and the total score. Respondents in stages III-V of the disease were 5.23 times (23%) likely to experience reduced QoL compared to those with less physical disability. In subjects suffering from MS reduced QoL was not related to the degree of clinical disability in physical, nor the mental dimension of the SF 36 and the total score. These results in MS patients can be partially explained by the small sample size, on the other hand it is possible that patients with MS, although they have greater physical disability seen as a very difficult diagnosis which determines the entire life. CONCLUSIONS: Patients who are treated for PD and MS had a high degree (> 80%) of reduction of the overall quality of life, and there were no significant differences in the extent of QoL reduction between these groups of patients. Reduced quality of life in patients with PD is observed during severe stages of the disease, while the QoL does not depent on the degree of clinical disability in MS patients. In both groups of patients the appearance patients reduced QoL does not depend on the duration of the disease. PMID- 22073855 TI - Etiological and clinical characteristics of lymphadenopathy at child age in Tuzla Canton. AB - Lymphadenopathy is defined as an abnormality in the size or character of lymph nodes, is caused by the invasion or propagation of either inflammatory cells or neoplastic cells into the node. Numerous factors, such as age, localization, size and consistency, present and previous pathological conditions are very important in order to define the future diagnostic and therapeutic course. OBJECTIVE: The aim of this study was to determine the etiological and clinical characteristics oflymphadenopathy in children in the area of the Tuzla Canton. PATIENTS AND METHODS: This retrospective-prospective study analyzed the medical records of the Department of Pediatrics in Tuzla of 334 patients in age from 0 to 14 years, in which the clinical signs of palpable lymph nodes of one or more regions was diagnosed in the period from January 1st 1998 to June 30th 2003. The anamnesis data, clinical findings, diagnostic procedures results, therapeutic approach and disease outcome etiology defined lymphadenopathy were analyzed. RESULTS: Out of 334 children, localized lymphadenopathy have been verified in 230, and generalized in 104. Male/female ratio was 1:1.8. Final results of our study have shown the etiologies as following: Infectious etiologies, 79.34%, neoplastic 11.34%, and non-neoplastic 9.28%. In neoplastic etiologies, lymphoblastic leukemia has been the most often verified neoplastic disease (68.4%), not related to the age or sex of patient, and equally presented as localized and generalized lymphadenopathy. In this study lymphomas were presented by generalized lymphadenopathy. CONCLUSION: The regional and generalized lymphadenopathy in children depends on their etiology and has significant prognostic value for the disease. PMID- 22073856 TI - Epidemiological and microbiological control of hospital infections in surgical patients. AB - INTRODUCTION: Intrahospital infections in surgical wards pose a significant problem, particularly in patients with impaired natural defense potential. They significantly complicate and increase the cost of basic treatment of the patient and sometimes leave permanent damage. Active control of their appearance is of paramount importance in their prevention. GOAL: By this study we try to determine the frequency of individual agents, their anatomical and gender distribution at the Clinic of Surgery, University Clinical Centre Tuzla in 2005.v. RESULTS: Our study showed that gram negative bacteria were more common trigger of IHI (76.37%), and especially the urinary and respiratory tract and surgical wounds infections. We also showed that men from older age groups are more likely to have IHI. CONCLUSION: Active surveillance and tracing for agents, especially in high risk groups of patients is the best method of prevention of IHI occurrence. PMID- 22073857 TI - Evaluation of working capacity in case of mental disorders. AB - Incidence of mental disorders in our country and in the world is growing and significantly impact working capacity. The goal of the study: to investigate which group of mental disorders and to what extent impacts the disability comparing two analyzed years (1999 and 2009). MATERIAL AND METHODS: 420 subjects were processed (143 in 1999 and 277 in 2009) from the Una-Sana Canton with mental disorders who were referred for evaluation of working capacity at professional authority in the first instance (Disability Commission) in Bihac. Disability Commission gave "Review, assessment and opinion" for each individual from which the author recorded data into the questionnaire necessary for the study. RESULTS: More men are sent for evaluation, aged 50 and over, who are not employed. Number of assessments has increased by almost double. The most addressed are from the group of affective disorders, who did not have disability during 1999 in majority, but in 2009 they are the leaders in disability, with schizophrenia. CONCLUSION: There is increased number of assessments, and most of them from the group of affective disorders whose participation in disability increases. Schizophrenia and affective disorders are the leading causes of disability. PMID- 22073858 TI - Factors affecting erectile function after radical prostatectomy. AB - INTRODUCTION: Radical retropubic prostatectomy is a therapeutic option for treatment of localized prostate cancer. The goal of radical prostatectomy is to completely remove the tumor while preserving erectile function and urinary continence as well as factors that determine the postoperative quality of life. There are many factors influencing sexual function after radical prostatectomy of localized prostate cancer. All factors can be divided into the preoperative, postoperative and intraoperative. In this paper we examine the significance of individual factors affecting erectile dysfunction following surgical treatment. MATERIAL AND METHODS: The study included 36 patients who underwent nerve sparing radical prostatectomy at the Urology Clinic, Clinical Center of Sarajevo University in period from January 2009 until December 2010. RESULTS: Out of 84 patients tested, radical retropubic prostatectomy with the reservation of neurovascular bundles was performed in 36 patients (42.8%). Of this number, both of the neurovascular bundles were preserved in 28 patients (77.7%) and one in 8 patients (22.2%). CONCLUSION: The positive predictive factor for erectile function after radical retropubic prostatectomy is the preoperative sexual function, younger age, preservation of both neurovascular bundles and early rehabilitation therapy. PMID- 22073859 TI - Surgical treatment and complications of treating pancreatic tumor. AB - Pancreatic tumor is one with the worst prognosis of all cancers, and the tenth most frequent cancer in Europe, making the 3% of all cancers affecting both sexes. Most patients seek treatment when the disease is in its advanced stage and the level for possible resectability is low. Late presentation of the disease is responsible for the short survival period of 6 months and a five-year survival of 0.4 to 5% of patients. At the Clinic for Surgery in Tuzla during period from January 1st 1996, to January 1st 2011, a total of 127 resection surgeries were performed due to malignant tumors. The goal of this study was to show that adequate assessment of operability, proper surgical strategy and modern techniques of creating anastomoses reduces morbidity and mortality, results in fewer postoperative complications and contributes to better surgical results. In our study sample the most common place of tumor location was the head of pancreas, in 69 (59.7%) patients. Men develop this type of cancer more often than women in the ratio of 2:1, while the median age of patients was 62 years. We faced postoperative complications in 37 (29.1%) patients, pancreatic fistula being the most prevalent complication, occurring in 16 (12.6%) patients. Overall early and late postoperative mortality was observed in 12 (9.8%) patients. CONCLUSION: Patients with chronic and hereditary pancreatitis are at a higher risk for developing pancreatic cancer and should be screened for the purpose of early diagnosis. The staging of pancreatic cancer has improved, with the accuracy of 85-90%. Postoperative complications, morbidity, and mortality are significantly reduced (p < 0.05) if the standardized operational procedure is applied and if modern techniques are used to create pancreaticojejunal anastomosis as the anastomosis carrying the highest risk. PMID- 22073860 TI - Extracorporeal fertilization in the world and in Croatia. AB - AIM: To point out the dangers, side effects and risks of medical assisted fertilization, in vitro fertilization, embryo transfer and injection on sperm in ovum for mother and the child. RESULTS: On the one hand the negative side effects for women of an abrupt rising risk for the development of neoplasm under pharmaceutical therapy are mentioned. Especially under a therapy which has the purpose to stimulate the ovulation of the ovary it lies around 100%. An increased level of certain hormones, as for example HCG, which influences the ovulation, is closely related with the risk of developing ovarian cancer. Clinical studies at more than 12000 infertile women (primary and secondary acyesis), with an average age of 30 years, show an elevated risk for the development of a malignant tumor of 98%. Also the application of Gonadotrophin is connected with a risk of 146% for the occurrence of cancer after a period of 15 years. FDT involves a risk of about 12% for the occurrence of breast cancer and shows also an aggravation for the risk of cancer of the endometrium from 79% up to 1152%. On the other hand the risk of spontaneous miscarriages under MAF, which is near 20%, and serious illness of the children, including 47% with need of intensive care unit support after birth, need to be realized. Furthermore the investigation of naturally obtained twins and through ART obtained twins shows in the arrangement a slower and poorer development of the children in the ART group with also great differences in physical development. In total the number of inherent malformation of newborns under the use of ART rises from 47 to 177%. With an installment of 9% we notice that children who came into being by IVF and ICS also fall more frequently ill. (Teething troubles, more hospitalizations and operations, higher frequency of major inherent malformations). CONCLUSION: All women who want to undergo a medical assisted fertilization should be informed about the side effects and risks for mother and child. PMID- 22073861 TI - Anesthesia for trans-sternal thymectomy: modified non-muscle relaxant technique. AB - Anesthesia for thymectomy in myasthenia gravis is challenging. Early surgical management is now considered to be an important therapeutic intervention for most of the patients of myasthenia gravis. The anesthetic experience of that technique is quite large. It involves either muscle relaxant or non-muscle relaxant techniques. However, the literature is deficient of standard anesthetic technique for thymectomy. Therefore we present in this report a modified non-muscle relaxant technique for thymectomy. We report one case with thymectomy under general anesthesia using fentanyl and propofol for induction and endotracheal intubation using non-muscle relaxant technique. The intubating, intraoperative and postoperative conditions were excellent. PMID- 22073862 TI - [(Pro)renin receptor /ATP6AP2 and cell death]. PMID- 22073863 TI - [BMP4-Smad1 signaling pathway in pathogenesis of diabetic nephropathy]. PMID- 22073864 TI - [HIF-1 in diabetic nephropathy]. PMID- 22073865 TI - [Sirt1 in diabetic nephropathy]. PMID- 22073866 TI - [Role of oxidative stress in pathogenesis of diabetic nephropathy]. PMID- 22073867 TI - [Microinflammation in diabetic nephropathy]. PMID- 22073868 TI - [Role of chemokines/chemokine receptors in pathogenesis of diabetic nephropathy]. PMID- 22073869 TI - [Difficult hemodialysis induction due to subclavian steal syndrome in a patient with Takayasu's arteritis]. AB - The patient was a 53-year-old woman who had bilateral renal arterial constriction due to Takayasu's arteritis, and developed end-stage renal failure. When transient loss of consciousness occurred in 2002, she was diagnosed with subclavian steal syndrome (SSS). The renal failure worsened in June 2004, and there was concern that the left SSS could become aggravated as a consequence of creating an arterio-venous (AV) shunt. Although peritoneal dialysis was strongly recommended, she elected to undergo hemodialysis. We confirmed that there was no reduction of cerebral blood flow using brain single photon emission computed tomography (SPECT). Right and left examinations indicated the site at which an AV shunt should be created and subsequently, the AV shunt was created on the left fore-arm. Brain SPECT findings were again confirmed after dialysis, at the time of hemodialysis induction, and again 2 years after hemodialysis induction, showing no reduction in cerebral blood flow. She has no apparent symptoms or signs of left SSS, to date. Although it is known that an SSS could arise after AV shunt creation, there has been no report of the creation of an AV shunt in a case of SSS. The present case suggests that cerebral blood flow measurement using brain SPECT is useful for evaluating cerebral hemodynamics before AV fistula creation among patients with Takayasu's arteritis. PMID- 22073870 TI - [Case of mixed connective tissue disease complicated with sarcoidosis and central diabetes insipidus]. AB - In 2003, a 64-year-old woman was diagnosed with mixed connective tissue disease and treated with oral prednisolone (30 mg/day). The prednisolone dose was gradually decreased, and a dose of 5 mg/day had been maintained since 2004. In 2009, she gradually developed vision loss, malaise, anorexia, and throat pain due to hydrodipsia. She was noted to have iritis and vitreous opacity by an ophthalmologist, and was referred for further evaluation. Fine rales were audible throughout the entire lung field, and chest CT showed diffuse small nodules that were more prominent on the upper and middle lobes, and swelling of the mediastinal and hilar lymph nodes. Transbronchial lung biopsy showed many epithelioid granulomas with multinuclear giant cells, compatible with sarcoidosis. Polyuria was identified as a cause of hydrodipsia and a diagnosis of partial central diabetes insipidus was made. High-dose prednisolone (40 mg/day) together with intranasal administration of desmopressin resulted in improvement of all of her clinical symptoms. MCTD followed by sarcoidosis is rare. Furthermore, this is the first reported case of MCTD complicated by sarcoidosis and central diabetes insipidus. PMID- 22073871 TI - [Case of peritubular capillary dominant intravascular large B-cell lymphoma (PTC dominant IVLBCL) successfully treated with chemotherapy]. AB - A 72-year-old woman developed common cold-like symptoms, diarrhea, a staggering gait, and persistent anorexia from the beginning of May 2009. In the middle of May, her general fatigue worsened, and she was transported to our hospital by ambulance. Abdominal CT showed bilateral renal enlargement, and her general condition and renal function rapidly deteriorated. The soluble interleukin-2 receptor (sIL-2R) level was elevated to 5,928 U/mL, and gallium scintigraphy showed a weak uptake in both kidneys. We considered the possibility of malignant lymphoma, and performed a renal biopsy, which showed no glomerular abnormalities, but disclosed the accumulation of large, atypical lymphoid cells with a high N/C ratio and dark chromatin in peritubular capillaries (PTC). On immunohistochemical staining, these atypical cells were found to be CD5(+), CD20 (+/-), CD10(-), CD3( ), and CD7(-), leading to a diagnosis of intravascular large B-cell lymphoma (IVLBCL). Since gallium scintigraphy showed no uptake in other organs, and examination of the cerebrospinal fluid and bone marrow revealed no tumor cells, the patient was considered to have kidney-limited IVLBCL. Chemotherapy was started immediately, which resulted in an improved general condition. Although her renal function deteriorated sufficiently to require dialysis, she was weaned from dialysis. After treatment with chemotherapy, the enlarged kidneys returned to the normal size. Subsequently, she has been receiving chemotherapy intermittently, and has remained free of recurrence. In general, IVLBCL mainly involving the kidney is difficult to diagnose antemortem, and is sometimes found at autopsy. We suggest that bilateral renal enlargement with renal failure of unknown origin should raise the suspicion of malignant lymphoma requiring a prompt renal biopsy. Cases of LBCL in which lymphoma cells fill PTC, as in this patient, have rarely been reported. We believe that this case is extremely valuable in understanding the pathogenesis of intravascular lymphoma invading the kidney; therefore, we report it with a review of the literature. PMID- 22073872 TI - [Case of MPO-ANCA-positive Wegener's granulomatosis with hepatitis C virus infection]. AB - A 77-year-old Japanese man was referred to our hospital because of the progression of renal dysfunction. Two months prior to the admission he had been diagnosed with otitis media. Urinalysis showed proteinuria and microscopic hematuria. Blood examination revealed renal dysfunction, hepatitis C virus (HCV)infection and positive myeloperoxidase (MPO)-ANCA. A chest CT revealed small infiltrates in the right middle lobe. The renal biopsy demonstrated crescentic glomerulonephritis with tubulitis. He was diagnosed as having Wegener's granulomatosis according to the American College of Rheumatology classification criteria. Methylprednisolone pulse therapy followed by oral prednisolone improved all of the otitis media, lung infiltrates and renal function. Recently, a high prevalence of ANCA has been reported in patients with HCV. It has also been reported that the prevalence of HCV infection is high in patients with Wegener's granulomatosis. Therefore, our case points to the clinical significance of HCV infection in ANCA-associated systemic vasculitis including Wegener's granulomatosis. PMID- 22073873 TI - UN high level summit on non communicable diseases. PMID- 22073874 TI - The Columbus effect: the donor community's "discovery" of non communicable diseases. AB - On 28-29 April, 2011 the First Global Ministerial on Healthy Lifestyles and Noncommunicable Diseases (NCDs) convened in Moscow to galvanize support and provide policy guidance for the forthcoming UN High-Level Meeting on NCDs in September 2011. Subsequently, the World Health Organization (WHO) drafted the "Moscow Declaration", placing itself at the global epicentre of NCD prevention and control, working collaboratively with its sole client in Member States, ministries of public health. The Declaration took no note of the extensive and ongoing activities of developing country owned and operated hospitals in the developing world and their clinical participation in NCD prevention and care for the past four decades. This article will review the global burden of NCDs in the developing world; the identification of NCDs by reliable sources decades before the "Moscow Declaration"; the role of hospitals in addressing them despite the absence of donor support; the considerable extant investments made by public and private entities in building inpatient and out-patient facilities; and how donors have overlooked the already established hospital-based industry within developing economies. PMID- 22073875 TI - NCD health literacy--what can hospitals do? AB - Noncommunicable disease (NCD) health literacy is a person's ability to access, understand and use information to prevent, treat and manage chronic illness. Poor health literacy is shown to be associated with riskier behaviour, poor health choices and poorer health. Hospitals can play an important role in enhancing people's NCD health literacy all the way along a patient's "NCD journey" from prevention to management by aligning their communications to the health literacy capacities of their users. The authors suggest training providers to communicate more effectively with patients, making their systems easier to navigate, simplifying written materials, incorporating the use of technology and mobile health, and using individual and system level scorecards and checklists. PMID- 22073876 TI - Dispositional and situational factors as determinants of food eating behaviour among sedentary and blue-collar workers in Nigeria's premier teaching hospital. AB - This cross-sectional survey investigated the role of dispositional (self-efficacy and self esteem), and situational factors (distractibility and perceived food variety) as determinants of food eating behaviour (FEB). Hospital employees (N500) in Nigeria's premier teaching Hospital participated. Results showed that self-efficacy and self-esteem jointly predicted cognitive restraint dimension of FEB (F(2499) = 26.00; R2 = 0.10; p < .05). Dispositional variables also jointly predicted uncontrolled eating (F(2499) = 17.41; R2 = 0.07; p < .05), emotional eating (F(2499)= 28.58; R2 = 0.10; p < .05), and cognitive restraint (F(2499) = 35.60; R2 = 0.13; p < .05) dimensions of FEB. Age (chi2 = 64.81; df = 1; p < .05), and marital status (chi2 = 32.74; df = 4; p < .05) were associated with FEB. Therefore, dispositional and situational variables are predictors of FEB as evidenced in previous literatures. The need for primary prevention, and assertiveness to reduce distractibility and eating disorders was highlighted towards maintaining health and efficiency at work is recommended. PMID- 22073877 TI - Comparative analysis of the quality of life in home and hospital treatment of patients suffering from heart failure. AB - This article presents an analytical examination of the results of the survey conducted by the specialized cardiac hospital for active treatment Pleven, which focused on the quality of life, hospital admission and death rate of patients suffering from heart failure that have already received hospital treatment. Given the specifics of the survey, patients were divided into two groups, one of which received ongoing follow-up care at home, while the other group did not receive this additional service. After twelve months, the results of the two groups were computed and collated according to three criteria - quality of life, subsequent hospital admission and death rate. The reported results of the group receiving ongoing specialized care were better in all three criteria. Based on this, the authors conclude that patients with treated heart failure should receive follow up care after they have been discharged, as this increases their quality of life and leads to fewer subsequent hospital admissions and death rates. PMID- 22073878 TI - Perceptions and experiences of co-delivery model for self-management training for clinicians working with patients with long-term conditions at three healthcare economies in U.K. AB - This paper presents a case study evaluation of self-management training courses for clinicians working with patients with COPD and Depression, at three NHS sites in United Kingdom. These courses were part of the Health Foundation's Co-Creating Health Initiative project and were co-delivered by a trained patient and clinician tutors. Interviews with 30 clinician attendees, four clinician tutors and two patient tutors suggested that the course content and delivery style were valued by everyone and clinicians reported a higher use of self-management skills following training. Analyses of the video-recorded consultation sessions of two trained clinicians showed limited use of co-production skills. PMID- 22073879 TI - Quo Vadis?: Russia's health challenges. AB - The roots of the health crisis in the Russian Federation are not entirely, or even primarily, in the state of the health care system. High levels of mortality and morbidity, particularly among working-age males, reflect many other factors that transcend the health system as they are related to the aging of the population, growing urbanization, lifestyles and risky behaviours. Spending more money on healthcare, while necessary, will not be sufficient to improve Russia's health outcomes on a sustainable basis. A multisectoral strategy is required, coupled with increased health expenditures and structural reforms to improve the efficiency and effectiveness of healthcare organization, financing and service delivery. However, it should be clear that improving health outcomes is a complex, medium- to long-term undertaking that should be addressed forcefully by the government at the federal and regional levels as a priority social objective. PMID- 22073880 TI - Over-hospitalization: an issue for hospital management. AB - The topic of this article is the insufficiently increasing rate of hospital admissions as a crucial factor for increasing hospital expenditures. The article focuses on the particular analysis of issues of induced hospital services demand, low level of effectiveness of the inpatient care system for referring, disproportions of accounted cases compared the need for therapies, patients' distrust toward lower sectors of healthcare, low efficiency of primary outpatient care and specialized outpatient care, lack of control, inadequate organization structure, strategy and improper NHIF regulation. The effective solving of these problems is a crucial term for improvement of the quality of inpatient care. PMID- 22073881 TI - [Effect of moxibustion-like thermal stimulation with different temperature and covering different areas of "zhongwan" (CV 12) on discharges of neurons in medullary subnucleus reticularis dorsalis of rats]. AB - OBJECTIVE: To observe the effect of regional thermal (moxibustion-like) stimulation on discharges of neurons in the medullary subnucleus reticularis dorsalis (SRD) and to study the best thermal stimulation parameters in the rat. METHODS: Experiments were performed on 15 male Sprague-Dawley rats under anesthesia (10% urethane, 1.0-1.5 g/kg). Unit discharges of single neurons in the medullary SRD were recorded extracellularly with glass micropipettes. Thermal stimulation (warm water filled in a glass bottle) with different temperature (40 degrees C, 42 degrees C, 44 degrees C, 46 degrees C, 48 degrees C, 50 degrees C, 52 degrees C) and covering different area (diameter: 1.0 cm x 1.5 cm, 2.0 cm, 2.5 cm, 3.0 cm, 3.5 cm, 4.0 cm) was applied to "Zhongwan"(CV 12) region for 30 s. Firing rates of SRD neurons were analyzed by using Power-Lab Chart 5.0. RESULTS: When thermal stimulation with temperature of 40 degrees C and 42 degrees C and the stimulated area of 1.0-4.0 cm in diameter was applied to CV 12 region, discharges of the medullary SRD neurons had no obvious changes. When the temperature was increased to 44 degrees C and 46 degrees C, the electrical activities of SRD neurons were increased linearly along with the increase of the stimulated area of 1.0-4.0 cm in diameter. When the temperature was increased further from 48 degrees C to 52 degrees C, the increased electrical activities of SRD neurons peaked at the stimulated area of 3.5 cm in diameter. In addition, thermal stimulation at a temperature of 50 degrees C and an area of 4.0 cm in diameter induced a larger increase of discharges of SRD neurons in comparison with that of 46 degrees C plus an area of 3.5 cm/4.0 cm in diameter (P < 0.05). No significant differences were found between 50 degrees C and 52 degrees C at any stimulated areas mentioned above (P > 0.05). CONCLUSION: Noxious thermal (44 52 degrees C) stimulation of CV 12 region can activate SRD neuron, which reaches a plateau when the stimulated area is increased to a certain range. PMID- 22073882 TI - [Effect of mild-warm moxibustion on microcirculation in the raw surface tissue of chronic refractory wound in skin ulcer rats]. AB - OBJECTIVE: To observe the effects of mild-warm moxibustion on dynamic blood flow, microvessel count (MVC)and vascular endothelial growth factor (VEGF) expression in the wound tissue of the chronic skin ulcer in rats, so as to reveal its underlying mechanism in promoting wound recovery. METHODS: A total of 104 male SD rats with skin injury were randomly divided into control group (n=8), model group (n=32), TDP (far-infrared heating device) group (n=32) and moxibustion group (n=32). Chronic refractory raw surface wound model was established by muscular injection of Hydrocortisone Sodium Succinate. For rats of the TDP and moxibustion groups, TDP irridiation and mild-warm moxibustion were applied to the raw surface, bilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 15 min, once daily for 3, 7 and 14 days respectively. The healing rate and the healing time of raw surface of the wound were observed. The blood flow of the raw surface of the wound tissue was measured by laser Doppler flowmeter and the MVC in granulation tissue of chronic skin ulcer was counted under light microscope. VEGF expression was detected by immunohistochemistry. RESULTS: In comparison with the control group, the healing rate of the wound raw surface was significantly lower and the healing time was prolonged in the model group (P < 0.01). Compared with the model group, the healing rates on day 3, 7, 10 and 14 were significantly higher and the healing time was strikingly faster in both TDP and moxibustion groups (P < 0.01, P < 0.05), and the effects of the moxibustion group in increasing the healing rate and shortening the healing time were significantly better than those of TDP group (P < 0.01). In comparison with the model group, the blood flow volume, MVC and VEGF expression levels on day 3 and 7 were upregulated significantly in both TDP and moxibustion groups (P < 0.01, P < 0.05); while the blood flow volume, MVC and VEGF expression level in the moxibustion group and the blood flow volume and VEGF expression level in the TDP group downregulated considerably on day 14 (P < 0.01). No significant difference was found between the TDP and moxibustion groups in the MVC on day 14 after the treatment (P > 0.05). CONCLUSION: Mild-warm moxibustion can promote wound healing, which is closely with its effects in increasing blood flow and MVC, and upregulating VEGF expression in the wound granulation tissue of the chronic skin ulcer. PMID- 22073883 TI - [Effect of electroacupuncture on differentiation and proliferation of hippocampal nerve stem cells in splenic asthenia pedo-rats]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the differentiation and proliferation of nerve stem cells in the hippocampal dentate gyrus (DG) in splenic asthenia pedo-rats so as to study its central mechanism. METHODS: A total of 72 SD male rats were randomly assigned to normal control group (n=24), model group (n=24) and EA group (n=24) which were further divided into 7 d, 14 d, 28 d and 49 d time-points (n=6). Splenic asthenia model was established by intraperitoneal injection of reserpine and gavage of Dahuang (Radix et Rhizoma Rhei) fluid. EA was applied to bilateral "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 20 min, once daily for 7, 14, 28 and 49 days respectively. Brdu, Nestin, glial fibrillary acidic protein (GFAP), and neuron specific enolase (NSE) expression in the DG of hippocampus were detected by immunohistochemistry double staining. RESULTS: Compared with the normal control group, the numbers of Brdu, Brdu/GFAP, Brdu/NSE Immunoreactive (IR) positive cells in the DG of hippocampus on day 7 and 14, and that of Brdu/Nestin IR positive cells on day 7 were decreased considerably in the model group (P < 0.05). Compared to the model group, the numbers of hippocampal Brdu IR-positive cells at the 4 time-points, Brdu/Nestin and Brdu/GFAP on day 7, 14 and 49, and Brdu/NSE on day 7, 14 and 28 were increased significantly in the EA group (P < 0.05). No significant differences were found between the model and control groups in the numbers of hippocampal Brdu and Brdu/NSE IR-positive cells on day 28 and 49, in the number of Brdu/Nestin IR-positive cells on day 14 and 49, in the number of Brdu/GFAP IR-positive cells on day 28; and between the EA and model groups in the numbers of Brdu/Nestin and Brdu/GFAP IR-positive cells on day 28, and in the number of Brdu/NSE IR-positive cells on day 49 (P > 0.05). CONCLUSION: EA of ST 36 and SP 6 can effectively suppress splenic asthenia syndrome-induced decrease of the numbers of Brdu, Brdu/GFAP, Brdu/Nestin and Brdu/NSE IR-positive cells in the DG of hippocampus at the early stage in the splenic asthenia rats, which may contribute to its effect in improving splenic asthenia symptoms in clinic by promoting the proliferation and differentiation of some nerve stem cells in the hippocampus. PMID- 22073884 TI - [Effect of electroacupuncture combined with intragastric administration of borneol on the permeability of blood-brain barrier in the mouse]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with gavage of borneol on the permeability and ultrastructure of the blood-brain barrier (BBB) in mice, so as to reveal its mechanism underlying improving permeability of BBB. METHODS: For assaying Evans blue (EB) content in the brain, 60 Kunming mice were evenly divided into control, EA, borneol (0.2 g/kg, borneol-0.2), borneol (0.4 g/kg, borneol-0.4), borneol (0.2 g/kg, borneol-0.2) + EA and borneol (0.4 g/kg, borneol-0.4) + EA groups. For determination of P-glycoprotein [P-gp, a member of the superfamily of ATP-binding cassette (ABC) transporters which transport various molecules across extra- and intra-cellular membranes] function and the ultrastructure of BBB, other 84 mice were randomized into control, borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA and verapamil groups (n=10 for P-gp. function analysis, and n 2 for electron microscopic observation). EA (2 Hz, 1 mA) was applied to "Baihui" (GV 20) and "Yamen"(GV 15) for 20 ml once daily for 14 days. EB (2.5%, 0.2 mL/kg) and rhodamine (Rh) 123 (0.2 mg/kg) were injected intravenously first through the tail vein, and their contents in the brain and Rh 123 in the plasma were detected after EA by using an ultraviolet fluorescence microplate reader. At the same time, the permeation index (Kp) was calculated by the ratio of Rh 123brain/Rh 123blood. RESULTS: Compared with the control group, the cerebral EB and Rh 123 contents and Kp of BBB in the EA, borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA and verapamil groups were increased significantly (P < 0.05, P < 0.01). The cerebral EB content was significantly higher in the borneol-0.2 + EA group than in the borneol-0.2 group (P < 0.05), suggesting a synergistic effect of EA and borneol. No significant differences were found among the EA, borneol-0.2 and borneol-0.4 groups in cerebral EB levels, among the control, EA, borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA and verapamil groups in plasma Rh 123 contents, and among the EA, borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA and verapamil groups in cerebral Rh 123 contents and Kp of BBB (P > 0.05). Results of the electron transmission microscope showed that the compact degree of the tight junction of BBB was decreased in the borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA groups but not in the EA group. CONCLUSION: EA and gavage of borneol treatments may enhance the permeability of BBB for EB and Rh 123 and have a certain synergistic effect in mice. The effect of borneol may be closely with the inhibition of P-glycoprotein and the decrease of tight junction of BBB while the effect of EA treatment is probably related to the inhibition of P glycoprotein only. PMID- 22073885 TI - [Effect of acupuncture on contents of beta-endorphin in the plasma and hypothalamus in rats with stress-induced gastric mucosal injury]. AB - OBJECTIVE: To explore the mechanism of acupuncture in preventing and treating stress-induced gastric mucosal injury from the view of brain-gut axis. METHODS: Forty male Wister rats were randomly divided into normal control, model 1, treatment, model 2 and prevention groups (n=8). Gastric mucosa injury model was established by intragastric perfusion of dehydrated alcohol (1.0 mL/rat). Rats of the treatment group were treated with acupuncture after modeling, while those of the prevention group treated first, followed by modeling. The time of modeling in model 1 group and model 2 group was simultaneous with that of the treatment group and prevention group respectively. Acupuncture was applied to "Zusanli"(ST 36), "Zhongwan" (CV 12) and "Neiguan" (PC 6) for 20 min, once daily for 5 days. Before sampling the tissues, 10% charcoal suspension was intragastric perfused 1 h for analyzing the rate of gastrointestinal propulsion(distance from the upper end of the charcoal powder to the cardia/total length of the cardia to the anus x 100%). Gastric mucosal ulcer index was measured by using Guth's method. The contents of beta-endorphin(beta-EP)in plasma and hypothalamus were determined by enzyme linked immunosorbent assay. RESULTS: Compared with the normal control group, the gastrointestinal propulsion rates were decreased considerably in the two model groups (P < 0.05), while the gastric mucosal ulcer indexes and the contents of beta-EP in both plasma and hypothalamus were increased significantly in the model groups (P < 0.05, P < 0.01). Compared with the corresponding model groups, the gastrointestinal propulsion rate was increased remarkably in the prevention group (P < 0.05), and the gastric mucosal ulcer indexes and the contents of plasma beta EP level were decreased obviously in both treatment and prevention groups (P < 0.05, P < 0.01). The contents of hypothalamic beta-EP were increased further in the later two groups (P < 0.01). CONCLUSION: Acupuncture of ST 36, CV 12 and PC 6 can promote the repair of gastric mucosal injury and improve gastrointestinal function, which may be related to its effects in reducing plasma beta-EP and upregulating hypothalamic beta-EP level. Acupuncture also has a better effect in preventing gastric mucosal injury. PMID- 22073886 TI - [Effect of electroacupuncture at different acupoints on plasma TXB2 and 6-keto PGF(1alpha), contents in dysmenorrhea rats]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) on plasma thromboxane B2(TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) levels in dysmenorrhea rats in order to investigate its mechanism underlying relief of primary dysmenorrhea and specificity of acupoint efficacy. METHODS: Female SD rats with diestrus were randomly divided into saline control (control), model, EA Sanyinjiao (SP 6), EA Xuehai (SP 10), EA Xuanzhong (GB 39) and EA non-acupoint (NAP) groups, with 10 rats in each. Dysmenorrhea model was established by subcutaneous injection of Estradiol Benzoate (0.5 mg/rat on the 1st and 10th day, and 0.2 mg/rat from the 2nd to the 9th day) and intraperitoneal injection of Oxytocin (0.2 mL/rat, 1 h after last injection of Estradiol Benzoate on the 10th day). EA was applied to bilateral SP 6, SP 10, GB 39, and non-acupoint (the mid point between the Gallbladder and Stomach meridian at the GB 39 level) for 20 min. The latency and score of writhing were recorded for 20 min. Plasma TXB2 and 6-keto-PGF1alpha contents were detected by radioimmunoassay. RESULTS: Compared with the control group, the latency of writhing in the model group was shortened considerably (P < 0.01), and the writhing score was increased significantly (P < 0.01). In comparison with the model group, the writhing latency was increased significantly only in the EA-SP 6 group (P < 0.05), and the writhing scores in the EA-SP 6, EA-SP 10, EA-GB 39 and EA-NAP groups were reduced remarkably (P < 0.01). Plasma TXB2 content and the ratio of TXB2/6-keto-PGF1alpha. were significantly higher in the model group than in the control group (P < 0.01). Compared to the model group, plasma TXB2 levels and the ratios of TXB2/6-keto PGF1alpha. in the EA-SP 6, EA-SP 10, EA-GB 39 and EA-NAP groups were downregulated markedly (P < 0.05, P < 0.01), while plasma 6-keto-PGF1alpha was upregulated strikingly only in the EA-SP 6 group (P < 0.05). No significant differences were found among the EA-SP 6, EA-SP 10, EA-GB 39 and EA-NAP groups in the writhing latency and writhing score, plasma TXB2 and 6-keto-PGF1alpha, levels (P > 0.05). CONCLUSION: EA can relieve pain reaction in dysmenorrhea rats, which may be closely associated with its effects in downregulating plasma TXB2, upregulating plasma 6-keto-PGF1alpha, content, and balancing plasma TXB2/6-keto PGF1alpha. The effect of EA of SP 6 is relatively better. PMID- 22073887 TI - [Effect of electroacupuncture on the levels of amino acid neurotransmitters in the spinal cord in rats with chronic constrictive injury]. AB - OBJECTIVE: To observe the changes of amino acid neurotransmitter contents in the lumbar spinal cord after electroacupuncture (EA) in rats with neuropathic pain so as to study its spinal mechanism underlying pain relief. METHODS: Forty SD rats were randomly divided into control, sham surgery, model and EA groups (n=10). Chronic constrictive injury (CCI) (neuropathic pain) model was duplicated by ligature of the right sciatic nerve with a piece of catgut. EA (1-3 mA, 2 Hz) was applied to "Huantiao" (GB 30) and "Weizhong" (BL 40) on the injured side for 30 minutes, once a day for 7 days. The mechanical and thermal pain thresholds were measured before and after CCI, and after EA intervention. Concentrations of glutamate (Glu), aspartate (Asp), glutamine (Gln), gamma-aminobutyric acid (GABA), Glycine (Gly) and taurine (Tau) in the lumbar spinal cord (L4-6) were detected by O-phthaladehyde derivatization + high performance liquid chromatography (HPLC). RESULTS: Compared with the control group, both the mechanical and thermal pain thresholds of the model group were decreased significantly on day 10 and day 16 after CCI (P < 0.01). Compared with the model group, the mechanical and thermal pain thresholds in the EA group on day 16 after CCI were upregulated strikingly (P < 0.01). In comparison with the control group, Glu, Asp, Gin and GABA levels in the lumbar spinal cord were significantly higher in the model group (P < 0.05, P < 0.01), while Gly and Tau levels in the lumbar spinal cord were markedly lower in the model group (P < 0.05). In comparison with the model group, spinal Glu, Asp, and Gin contents were downregulated significantly in the EA group (P < 0.01), while Gly, GABA and Tau levels were upregulated obviously (P < 0.01, P < 0.05). No significant differences were found between the control and sham surgery groups in the mechanical and thermal pain thresholds, and in the spinal Glu, Asp, GIn, GABA, Gly and Tau levels (P > 0.05). CONCLUSION: EA of GB 30 and BL 40 may alleviate neuropathic pain in CCI rats, which is closely with its effects in reducing the release of excitatory amino acids and promoting the release of inhibitory amino acid neurotransmitters. PMID- 22073888 TI - [Effects of balance-acupuncture stimulation of "back pain" and "hip pain" points on plasma beta-endorphin and ACTH contents in rats with lumbar disc herniation]. AB - OBJECTIVE: To observe the effect of balance acupuncture on the thermal pain threshold and plasma beta-endorphin (beta-EP) and adrenocorticotrophic hormone (ACTH) levels in lumbar disc herniation rats so as to research its mechanisms underlying improvement of lumbar disc protrusion. METHODS: A total of 120 male rats were randomly divided into blank control (control) group, model group, sham operation(sham)group, and acupuncture group (n=30) which were further divided into 7-days (d) and 14-d subgroups. Rats in the acupuncture group were treated with balance acupuncture of "Back Pain" point (the midpoint between two eyes) and "Hip Pain"point (the midpoint between the acromial process and the axillary furrow). Thermal pain threshold was detected by using radiant heat detector. Plasma beta-EP and ACTH levels were determined by radioimmunoassay. RESULTS: Compared with the control group and pre-operation and sham group, the thermal pain reaction was increased significantly in the model group (P < 0.05). In comparison with the model group, the thermal pain reaction was decreased obviously from day 10 after acupuncture treatment in the acupuncture group (P < 0.05). Compared to the control group, plasma beta-EP contents on day 7 and 14 and ACTH level on day 14 in the model group were increased significantly (P < 0.05), while in comparison with the model group, plasma beta-EP contents on day 7 and 14 and ACTH level on day 14 in the acupuncture group were down-regulated markedly (P < 0.05). No significant difference were found between the control and sham groups in plasma beta-EP contents and ACTH levels on day 7 and 14 (P > 0.05). CONCLUSION: Balance acupuncture treatment can lower plasma ACTH level in lumbar disc herniation rats, which may contribute to its effect in easing lumbar disc herniation pain in clinic practice. PMID- 22073889 TI - [Observation on the anti-stress effect of acupuncture-assisted anesthesia for puhnlmonary lobectomy patients]. AB - OBJECTIVE: To observe the anti-stress effect of acupuncture-assisted anesthesia in patients undergoing pulmonary lobectomy. METHODS: A randomized, controlled, single-blind clinical trial was conducted in the present study. A total of 48 patients undergoing pulmonary lobectomy were randomized into regular general anesthesia (RGA), general anesthesia combined with 2 Hz electroacupuncture (EA) (GA+2 Hz-EA), general anesthesia combined with 2 Hz/100 Hz EA (GA+2 Hz/100 Hz EA), and GA + 100 Hz-EA groups (n=12). EA (1-3 mA) was applied to bilateral Houxi (SI 3), Zhigou (SJ 6), Neiguan (PC 6) and Hegu (LI 4) for 30 min, followed by general anesthesia with midazolam (0.05 mg/kg), fentanyl (5 microg/kg), propofol (2 mg/kg), and vecuronium (0.1 mg/kg). The dosages of the anesthetics, heart rate (HR), systolic blood pressure (SBP), and bispectral index (BIS) of electroencephalogam during general anesthesia were recorded. Plasma adrenaline and cortisol concentrations were assayed by radioimmunoassay. RESULTS: In comparison with the RGA group, the dosages of supplementary propofol and fentanyl in both GA + 2 Hz-EA and GA + 100 Hz-EA groups,and that of propofol in the GA+2 Hz/100 Hz-EA group were decreased significantly (P < 0.05, P < 0.01). Compared to the RGA group, both HR and SBP values during trachea extubation in the GA+ 2 Hz/100 Hz-EA and GA + 100 Hz-EA groups were significantly lower (P < 0.01, P < 0.05). No significant differences were found between the GA+2 Hz/100 Hz-EA and RGA groups in the supplementary dose of fentanyl, between the GA+2 Hz-EA and RGA groups in HR and SBP values during trachea extubation, among the 4 groups in HR and SBP values before trachea extubation and in plasma adrenaline and cortisol levels (P > 0.05). CONCLUSION: Acupuncture-assisted anesthesia can decrease the dosage of general anesthetics, and effectively restrain cardiovascular stress reaction during trachea extubation in pulmonery lobectomy patients. PMID- 22073890 TI - [Electroacupuncture at Guanyuan (CV 4) and Zhongwan (CV 12) modulates functional connectivity of the brain network in healthy volunteers]. AB - OBJECTIVE: To observe the specific brain effects of electroacupuncture (EA) stimulation of Guanyuan (CV 4) and Zhongwan (CV 12). METHODS: Twenty-one healthy volunteers were recruited in the present study. Two silver filiform needles were separately inserted into Guanyuan (OV 4) or Zhongwan (CV 12), and manipulated with uniform reducing-reinforcing method to induce "Deqi". fMRI scan was performed before needling, during needle retention, EA stimulation, and post-EA. Data of fMRI was analyzed by using software SPM 2. The volunteer subjective needling sensations were recorded. The activation, deactivation, short-distance and long-distance functional connectivity maps of different cerebral regions were analyzed by using whole brain correlation analysis. RESULTS: Comparison between the two acupoints showed that fullness feeling was stronger in CV 4 than in CV 12. EA at CV 4 and CV 12 induced a similar stronger and prevalent deactivation in the ventral medial prefrontal cortex and the anterior cingulated cortex (ACO). The deactivation of the ACC was stronger in the CV 4 group than in the CV 12 group. The default BOLD mode of the brain at rest was modified by needle retention and EA, respectively. The short-distance functional connection brain network was significantly changed after EA. Interestingly, the ventral medial prefrontal cortex and anteroinferior portion of the anterior cingulate cortex in the limbic-paralimbic-neocortical network (LPNN) were involved in the instant post-effects of EA. Relatively smaller differences in the brain functional activity and short-distance functional connectivity were found between these two acupoints. CONCLUSION: EA of CV 4 and CV 12 can modulate short-distance functional connectivity of the LPNN, and have fewer differences in inducing needling sensation and deactivation of ACC, etc. PMID- 22073891 TI - [Randomized controlled clinical trails for treatment of knee osteoarthritis by warm acupuncture combined with intra-articular injection of sodium hyaluronate]. AB - OBJECTIVE: To observe the synergism of warm acupuncture combined with intra articular injection of sodium hyaluronate on knee osteoarthritis (KOA). METHODS: A total of 179 KOA outpatients were randomized into warm acupuncture group (n=90) and control group (n=89) according to a randomized numeral table. Warm acupuncture (needle warmed by moxibustion) was applied to Zusanli (ST 36), Xuehai (SP 10), Yinlingquan (SP 9), Neixiyan(EX-LE4), etc. from the second day on after intra-articular Injection of sodium hyaluronate (2 mL, once a week for 5 weeks). Sodium hyaluronate intra-articular injection was given to the patients alone in the control group. Knee joint motor function was scaled before, 2 weeks (W) and 5 W after the therapy. The patients' quality of life was determined by using "Arthritis Impact Measurement Scale" before and 5 W after the therapy. RESULTS: In comparison with pre-therapy, the knee-joint motor function scores of both control group and acupuncture group were increased progressively and significantly 2 W and 5 W after the therapy. Both the knee-joint motor function score and the therapeutic effective rate of the acupuncture group were significantly higher than those of the control group (P<0.001, P<0.05). After the therapy, the scores of the Arthritis Impact Measurement Scale were significantly improved in both groups (P<0.01), and that of the acupuncture group was obviously lower than that of the control group (P<0.01). CONCLUSION: Warm acupuncture combined with intra-articular injection of sodium hyaluronate is an effective therapy for knee osteoarthritis. PMID- 22073892 TI - [False dissemination of "treatment of hemorrhoids by acupuncture of Kongzui (LU 6)" and its unfavorable influence on modern acupuncture]. AB - "Treatment of hemorrhoids by acupuncture of Kongzui (LU 6)" has been considered to be an example of new discovery in current clinical acupuncture practice and has produced a significant influence on domestic and foreign textbooks of acupuncturology and the health care of the people. After comprehensively analyzing this known saying, it was found that the so-called "new discovery" which has been inherited for decades of years is in fact derived from incorrect dissemination, being lack of evidence of both literature and clinical practice. PMID- 22073893 TI - [Our viewpoints on relationship between discovery of meridians and pulse-feeling diagnosis]. AB - Some scholars believe that the ancient Chinese physicians found meridian phenomena on the basis of pulse-feeling diagnosis. But the authors of the present paper don't think so, and that the relationship between the discovery of meridian phenomena and pulse-feeling diagnosis is not so simple. In the present paper, the authors analyze their correlation from the following 6 points. (1) In ancient China, the difference between the pulse-feeling locations on the human body and the number of clinical disorders is huge, which is very difficult to make them to be corresponding. (2) Shenmen (HT 7), one acupoint of the Heart Meridian of Hand Shaoyin and one of the positions for pulse-feeling diagnosis, is not identical to the running course of meridians described in the early historic stage of China. (3) Taking the corresponding correlation between the upper-lower parts of the Meridian of Hand-Yangming to make a deduction on other meridians is definitely jug-handled. (4) It is logically unreasonable to demonstrate the relationship between the meridian and pulse-feeling diagnosis by taking the Luomai (collaterals of meridian) as the example. (5) The running pathways of the Eight Extra-meridians which also belong to the meridian system are not identical to the regularities of "Biao" "Ben" pulses. (6) In the ethnic traditional medicine, there exists an upper-lower corresponding pulse diagnosis, but, no similar text descriptions have been found in the medical works on meridians. Therefore, the meridian system is not found by means of pulse-feeling diagnosis, and rather, the meridian theory promotes the development of pulse-feeling diagnosis in clinical practice. PMID- 22073894 TI - [Development of studies on neurochemical mechanism of acupuncture underlying improvement of depression]. AB - Chronic stress often results in neurochemical changes in the central nervous system and may lead to the onset of depression. These neurochemical changes refer to alterations of activities of neurotransmitters, neuromediators, hormones and neuronal plasticity, etc. The underlying mechanism of acupuncture in the antidepressant effect is related to its regulatory effect on the neurochemical imbalance. In the present review, the authors summarize the progress of experimental researches on acupuncture treatment of depression from (1) monoamines neurotransmitters and their receptors, (2) gamma-aminobutyric acid and glutamate, (3) neuropeptide Y, (4) hypothalamus-pituitary-adrenal axis and hypothalamus-pituitary-throid axis activities, and (5) brain-derived neurotrophic factor. In addition, the authors also make an evaluation on the insufficiency of current studies and put forwards some suggestions on the future study. PMID- 22073895 TI - [Overview of researches on the underlying mechanism of that "Hegu (LI 4) is indicated for orofacial disorders"]. AB - It has been well documented in Chinese acupuncture medicine that "Hegu (LI 4) is indicated for orofacial problems". In the present paper, the authors analyze their correlation from the learning of modern medicine and results of recent experimental studies instead of traditional meridian theory of acupuncturology. The afferent nerve fibers from the LI 4 region and the orofacial part ascend to the spinal cord, nucleus of solitary tract, reticular formation, thalamus and the cerebral cortex, respectively, and overlap in the thalamus, cerebral cortex, etc. Under the circumstances, the interaction and functional integration of the afferent signals from LI 4 acupoint and the orofacial region may occur in the central nervous system. In addition, many relevant neuroactive substances (for example, serotonin, substance P, enkephalin, y-aminobutyric acid, glycine, calcitonin gene-related peptide, etc.) released from the sensory and motor neurons in the corresponding cerebral regions may constitute part of the substantial basis of that "Hegu (LI 4) is indicated for many orofacial disorders". PMID- 22073896 TI - Let's leave bullying on the playground! PMID- 22073897 TI - Ins and outs of suprapubic catheters--a clinician's experience. AB - In today's evolving health care field, outpatient procedures are becoming more commonplace. Many patients with suprapubic catheters are now being seen in outpatient or home care settings. Addressing the educational needs of patients, family members, and nursing staff is now more important than ever for successful patient suprapubic catheter management. A basic understanding of how these catheters are initially placed is essential for proper care and avoidance of possible complications. This review of initial placement of suprapubic catheters and post-insertion care is based on one clinician's experience and practice at a local hospital in Pennsylvania. PMID- 22073898 TI - Vaginal diazepam use with urogenital pain/pelvic floor dysfunction: serum diazepam levels and efficacy data. AB - Vaginal diazepam is used off-label for pelvic floor dysfunction and urogenital pain, but serum levels with efficacy have not been reported until now. One clinician evaluated 21 women for overall, levator, and vulvar pain pre- and one month post-daily diazepam treatment. One-month post-treatment assessments and serum diazepam levels were done; 62% were moderately or markedly improved. Levator examination pain scores were significantly improved, and vulvar pain scores decreased post-treatment. Serum diazepam levels were within normal limits. Vaginal diazepam may be helpful in treating pelvic floor/urogenital pain conditions. PMID- 22073899 TI - Desmopressin versus behavioral modifications as initial treatment of primary nocturnal enuresis. AB - The purpose of this study was to compare the effectiveness of desmopressin to behavioral modifications as the initial treatment of primary monosymptomatic nocturnal enuresis (PMNE). Study results determined that either intervention led to a significant reduction in PMNE episodes. These results suggest that either method is equally effective for treatment of PMNE. PMID- 22073900 TI - The lonely female partner: a central aspect of prostate cancer. AB - The aim of this qualitative study was to investigate the experiences of female partners to men with prostate cancer. The women found the capacity to manage their lives through mutual love in the family and through their faith. PMID- 22073901 TI - Adding to the evidence base: The lonely female partner: a central aspect of prostate cancer. PMID- 22073902 TI - Entrapped Foley catheter: a case study. AB - Obstruction of the urethra can cause necrosis of the urethra. Without prompt intervention, this obstruction may lead to intrinsic renal failure. A unique nursing situation occurred with a patient's entrapped Foley catheter, requiring timely intervention. This case study reinforces that a nurse's ability to assess and describe clinical assessment findings to a physician via the telephone can be critical to patient outcomes. PMID- 22073903 TI - Characteristics and impact of interrupted sleep in women with overactive bladder. AB - Women who self-report symptoms of overactive bladder (OAB), including nocturia, experience significant sleep deficits and a diminished quality of life. These deficits and their impacts are greater among women who awaken two or more times per night. When evaluating patients with OAB, it is important for clinicians to assess sleep habits and practices in addition to bladder symptoms to fully gauge the health and well-being of women with OAB. PMID- 22073904 TI - European Escherichia coli O104:H4 outbreak. PMID- 22073905 TI - Integrated circuits and logic operations based on single-layer MoS2. AB - Logic circuits and the ability to amplify electrical signals form the functional backbone of electronics along with the possibility to integrate multiple elements on the same chip. The miniaturization of electronic circuits is expected to reach fundamental limits in the near future. Two-dimensional materials such as single layer MoS(2) represent the ultimate limit of miniaturization in the vertical dimension, are interesting as building blocks of low-power nanoelectronic devices, and are suitable for integration due to their planar geometry. Because they are less than 1 nm thin, 2D materials in transistors could also lead to reduced short channel effects and result in fabrication of smaller and more power efficient transistors. Here, we report on the first integrated circuit based on a two-dimensional semiconductor MoS(2). Our integrated circuits are capable of operating as inverters, converting logical "1" into logical "0", with room temperature voltage gain higher than 1, making them suitable for incorporation into digital circuits. We also show that electrical circuits composed of single layer MoS(2) transistors are capable of performing the NOR logic operation, the basis from which all logical operations and full digital functionality can be deduced. PMID- 22073906 TI - Enhanced affinity bifunctional bisphosphonates for targeted delivery of therapeutic agents to bone. AB - Skeletal diseases have a major impact on the worldwide population and economy. Although several therapeutic agents and treatments are available for addressing bone diseases, they are not being fully utilized because of their uptake in nontargeted sites and related side effects. Active targeting with controlled delivery is an ideal approach for treatment of such diseases. Because bisphosphonates are known to have high affinity to bone and are being widely used in treatment of osteoporosis, they are well-suited for drug targeting to bone. In this study, a targeted delivery of therapeutic agent to resorption sites and wound healing sites of bone was explored. Toward this goal, bifunctional hydrazine-bisphosphonates (HBPs), with spacers of various lengths, were synthesized and studied for their enhanced affinity to bone. Crystal growth inhibition studies showed that these HBPs have high affinity to hydroxyapatite, and HBPs with shorter spacers bind more strongly than alendronate to hydroxyapatite. The HBPs did not affect proliferation of MC3T3-E1 preosteoblasts, did not induce apoptosis, and were not cytotoxic at the concentration range tested (10(-6)-10(-4) M). Furthermore, drugs can be linked to the HBPs through a hydrazone linkage that is cleavable at the low pH of bone resorption and wound healing sites, leading to release of the drug. This was demonstrated using hydroxyapatite as a model material of bone and 4-nitrobenzaldehyde as a model drug. This study suggests that these HBPs could be used for targeted delivery of therapeutic agents to bone. PMID- 22073907 TI - Biochemical and immunochemical characterization of different varieties of amaranth (Amaranthus L. ssp.) as a safe ingredient for gluten-free products. AB - Celiac disease is a food intolerance triggered by the ingestion of gluten containing cereals; the only therapy is a strict gluten-free diet for life. In recent years, amaranth flour has received considerable attention as an interesting source for the formulation of gluten-free products due to its high nutritional value and low content of prolamins, the toxic proteins for celiacs. The aim of this study was to characterize 40 amaranth varieties using both SDS PAGE/immunoblotting and ELISA to assess their possible tolerance by celiac subjects. All of the amaranth samples studied showed similar binding affinities for both specific anti-gliadin antibodies and human IgAs. In most amaranth grains, the content of gluten-like proteins measured by ELISA was <20 ppm. The molecular characterization of amaranth proteins suggests that amaranth is safe for celiacs to consume. It is recommended that the most suitable amaranth varieties are those having the lowest content of proteins cross-reacting with anti-gliadin antibodies. PMID- 22073909 TI - A prospective phase II trial of vinblastine and methotrexate in multivessel intraluminal pulmonary vein stenosis in infants and children. AB - OBJECTIVE: To determine the safety and efficacy of the chemotherapeutic agents vinblastine and methotrexate in the treatment of children with progressive multivessel intraluminal pulmonary vein stenosis (PVS). METHODS: Children received weekly vinblastine and methotrexate for a period of 1 year. Outcomes (for patients receiving >=1 month of chemotherapy) were classified separately for patients with isolated PVS and PVS with congenital heart disease (CHD). Primary efficacy outcome was "response to treatment" categorized by echocardiographic criteria of response. Survival to 1 year was also evaluated. All adverse events were classified according to Cancer Therapy Evaluation Program, Common Terminology Criteria version 3.0. Events were further classified as related to chemotherapy, cardiac, or other causes. RESULTS: Among 29 patients enrolled, 28 received at least one dose of chemotherapy and were evaluable for toxicity, while 23 were evaluable for response (21 CHD, 2 isolated). Both patients in the isolated group had progressive disease and died. Overall, 33% (7/21) of patients with PVS and CHD had stable disease; 1-year survival of 38%; and four patients continue in remission (93, 96, 124, and 125 months after treatment initiation). While both cardiac-related (19%) and chemotherapy-related (53%) toxicities were common, most were asymptomatic laboratory changes. Grade 3 (13%) and grade 4 (4%) toxicities were reversible, and no treatment-related grade 5 toxicities were observed. CONCLUSION: We report on the first prospective trial of chemotherapy for infants and children targeting the presence of myofibroblastic cells within the lesions of PVS based on myofibroblastic proliferation associated with desmoid tumors of infancy. The toxicity profile resulted in numerous treatment delays and interruptions that, combined with limited information on the natural history of PVS in this patient population, hampered our ability to determine the true efficacy of this approach. These results will be important as a baseline for clinical trials in this patient population. PMID- 22073910 TI - Fertility differences in Peru: A reconsideration. AB - Abstract In a series of articles by Stycos, Heer and W. H. James, predominantly Indian areas of Peru were reported to have significantly lower levels of fertility than the economically better developed Spanish-speaking areas. Heer and James reported similar findings for Bolivia and Ecuador as well as Peru. PMID- 22073911 TI - Estimation of vital rates for Ghana. AB - Abstract A complete and efficient registration system, of the type which would provide good data on births and deaths, does not exist in Ghana. However, registration of vital events is supposed to be compulsory in 39 towns in the country but the data collected in these areas are too inadequate and defective to provide a sound basis for the analysis of the dynamics of population growth. The results of the censuses conducted by the colonial governments are so defective and unreliable that they do not allow scientific research in the field of population analysis. Before 1960, therefore, when the national census and the post-enumeration survey (based on a 5% sample of the population) were carried out, estimates of fertility and mortality levels were little more than guesses. In this study an attempt has been made to utilize the information on the age-sex composition provided by the 1960 census and post-enumeration survey data on births and deaths to determine, as far as possible, the levels of fertility and mortality and the rates of population growth in Ghana. The fertility estimates i.e. a crude birth rate of 50, total fertility rate of 6.9 and a gross reproduction rate of 3.4-show that Ghana's fertility is one of the highest in the world. An expectation of life at birth of 40 years, an infant mortality of 160 and a crude death rate of 23 appear to be the most plausible estimates. These estimates yield a rate of natural increase of 2.7% and a growth rate of 3.0% per annum. PMID- 22073912 TI - Time series of growth in use of oral contraception and the differential diffusion of oral anovulents. AB - Abstract Differential growth in the use of oral anovulents is explored through construction of separate time series for Canadian women classified by religion, education, and nativity. The series suggest that native-born Roman Catholic women are as likely as native-born Protestant women to be using oral contraceptives by the terminal point of our series in 1967. The period of very rapid growth in the use of orals appears to have come to an end. Differential patterns of diffusion of oral contraception shown by the categories of women discussed, suggest sources of bias in the profile of an aggregate time series. PMID- 22073913 TI - Buddhist factors in population growth and control A survey based on Thailand and Ceylon *. AB - Abstract Although Buddist doctrine and institutions do not directly encourage the procreation of children, the Buddhist countries of South Asia (for the purposes of this paper, Ceylon, Burma, Thailand and Cambodia) have high fertility rates. The first half of this paper is devoted to examining possible reasons for this: particularly, whether there are non-Buddhist factors which produce high fertility and outweigh the negative Buddhist attitude, or whether there are less obvious factors within the structure of Buddhist culture which tend to produce high fertility indirectly; this preliminary review of evidence favours the latter explanation. In the second half of the paper South Asian Buddhist attitudes to policies of population control are examined. While in theory there is no Buddhist opposition to family planning, apart from the general Buddhist rejection of abortion, some differences of attitude towards other methods are observable between Ceylon and Thailand, the Buddhist opposition to contraception being stronger in the former than in the latter. It is suggested that the differences in attitude may be due to the larger proportion of non-Buddhists in the population of Ceylon than in Thailand, although the opposition is expressed in primarily doctrinal terms. PMID- 22073914 TI - The value of avoided births to underdeveloped countries. AB - Abstract An estimate of the value to a developing economy of preventing an additional birth is a useful yardstick for decisions about bonuses, information and-dispensation campaigns, and propaganda campaigns. Enke's method of estimation incorrectly reckons private costs as public costs and attributes all the avoided consumption of the prevented child to the social account, whereas most of it would be otherwise consumed by the child's family. And at the discount rate Enke uses (15%) the effect of an added child on the marginal productivity of other workers is irrelevant. On the other hand, a 15% discount is shown to be inconsistent with other governmental decisions, and a lower discount rate reduces the value of a prevented birth in Enke's scheme. Hence Enke's method is internally inconsistent. Coale and Hoover's work on India enables one to generate an estimate for the value of an avoided birth on the basis of a complete and realistic macro-economic system. This was done by relating the differences in numbers of births in future periods (under two of the Coale-Hoover alternatives) to the differences in aggregate income that are projected (under the two alternatives). Even at the high discount rate of 15%, the value is $114. At lower discount rates the value is much higher. PMID- 22073915 TI - Fecundability and its relation to age in a sample of Taiwanese women. AB - Abstract In this paper reliable estimates of mean fecundability at marriage for a sample of heterogeneous Taiwanese women are obtained by using a set of data collected retrospectively. The effects of 'truncation bias' and 'memory bias' are estimated by studying the relationships between mean fecundability and the duration of marriage. Then the variations in fecundabilities by age at marriage are studied. The data are taken from an intensive fertility survey of married women between the ages of 20 and 39 conducted in Taichung city of Taiwan towards the end of 1962 prior to a year-long family planning action programme. Fecundability, the probability of conception in the absence of contraception, is estimated by using a Type I geometric model and is estimated from the observed distribution of first pregnancy intervals-the period between the onset of marriage and the beginning of first conception. The estimated fecundability level relatively free from truncation and memory bias is 195+/-3 per 1.000 women. The fecundability level increases with wife's age at marriage (up to 25) independently of its association with the duration of marriage. PMID- 22073916 TI - Local censuses in the 18th century. AB - Abstract Recent work on the population problems of the eighteenth century has been mainly based on the use of parish records. Another source, and one which, surprisingly, has received little attention is the local census. These are more numerous than is generally realised; and can be of great use in demographic studies. This paper examines 125 local censuses mainly taken in urban areas. They are discussed in terms of how they come to be taken, their reliability, extant manuscript material and their contents. Whilst most of the censuses confine themselves to the basic facts such as total population, number of houses and number of families, some give details of sex, age, marital status and occupation. Generally the information is given for the parish or local administrative unit, but in a few instances it is available by streets. PMID- 22073917 TI - Some comments on article by K. Srinivasan: 'A probability model applicable to the study of inter-live birth intervals and random segments of the same'. AB - Abstract This paper discusses a probability model of birth intervals, proposed by K. Srinivasan, for the study of data collected in some fertility surveys. New formulae for mean and variance of the "open interval" distribution are given. PMID- 22073918 TI - The causes of induced abortion. AB - Abstract In drawing conclusions about the causes of induced abortion, Treffers (Population Studies 20, pp. 295ff) assumed that spontaneous abortion is unrelated to psychological and sociological variables. It is suggested that these assumptions may be false. Some remarks are appended on the mode of ascertainment of abortions and its relation to their estimated incidence. PMID- 22073919 TI - The demographic effects of a contraceptive programme. AB - Abstract The calculation of the number of births prevented for each item of contraceptive service provided entails the integration of a variety of factors relating to the potential fertility of users and the duration and effectiveness of use. This article differs from previous essays of this kind in that estimates of future potential fertility are based not on fertility rates but on age specific means of inter-live birth intervals, modified by periods of use overlapping post-partum sterility, and by the probabilities attached to the development of permanent sterility and to the successful adoption of extra programme birth control. In the first three years after acceptance of intra uterine contraception by some 9,000 postpartum women of several ethnic origins in Singapore, it is calculated that about 4,800 births were prevented. PMID- 22073922 TI - Influenza immunization in egg allergy: an update for the 2011-2012 season. AB - Flu vaccines contain detectable amounts of egg protein, which may pose a risk to egg-allergic individuals. The 2009 H1N1 influenza pandemic required mass vaccination in many countries, and the safety of flu immunization in egg allergy became of increasing public health importance. This article reviews recent literature and provides an updated guideline for immunization during the 2011 2012 flu season. Recent experience suggests that some vaccines with very low ovalbumin concentrations may be safe for use in primary care in carefully assessed low-risk individuals. PMID- 22073923 TI - The impact of laxative use upon symptoms in patients with proven slow transit constipation. AB - BACKGROUND: Constipation severity is often defined by symptoms including feelings of complete evacuation, straining, stool frequency and consistency. These descriptors are mostly obtained in the absence of laxative use. For many constipated patients laxative usage is ubiquitous and long standing. Our aim was to determine the impact of laxative use upon the stereotypic constipation descriptors. METHODS: Patients with confirmed slow transit constipation completed 3-week stool diaries, detailing stool frequency and form, straining, laxative use and pain and bloating scores. Each diary day was classified as being under laxative affect (laxative affected days) or not (laxative unaffected days). Unconditional logistic regression was used to assess the affects of laxatives on constipation symptoms. RESULTS: Ninety four patients with scintigraphically confirmed slow transit constipation were enrolled in the study. These patients reported a stool frequency of 5.6 +/- 4.3 bowel motions/week, only 21 patients reported <3 bowel motions/week. Similarly, 21 patients reported a predominant hard stool at defecation. The majority (90%) of patients reported regular straining. A regular feeling of complete evacuation was reported in just 7 patients. Daily pain and/or bloating were reported by 92% of patients. When compared with laxative unaffected days, on the laxative affected days patients had a higher stool frequency (OR 2.23; P <0.001) and were more likely to report loose stools (OR 1.64; P <0.009). Laxatives did not increase the number of bowel actions associated with a feeling of complete evacuation. Laxative use had no affect upon straining, pain or bloating scores CONCLUSIONS: The reporting of frequent and loose stools with abdominal pain and/or bloating is common in patients with slow transit constipation. While laxative use is a significant contributor to altering stool frequency and form, laxatives have no apparent affect on pain or bloating or upon a patients feeling of complete evacuation. These factors need to be taken into account when using constipation symptoms to define this population. PMID- 22073924 TI - Synthesis of 2-naphthols via carbonylative Stille coupling reaction of 2 bromobenzyl bromides with tributylallylstannane followed by the Heck reaction. AB - A method for the synthesis of 2-naphthols 4 is described. The carbonylative Stille coupling reactions of 2-bromobenzyl bromides with tributylallylstannane to produce 2-bromobenzyl beta,gamma-unsaturated ketones 2 in satisfactory to excellent yields has been achieved. The isomerization of 2-bromobenzyl beta,gamma unsaturated ketones 2 can readily occur under basic conditions to generate 2 bromobenzyl alpha,beta-unsaturated ketones 3. The 2-bromobenzyl alpha,beta unsaturated ketones 3 can be transformed into 2-naphthols 4 via intramolecular Heck reaction in satisfactory to good yields. PMID- 22073925 TI - Single kaolinite nanometer layers prepared by an in situ polymerization exfoliation process in the presence of ionic liquids. AB - A simple chemical route for the exfoliation of kaolinite in the presence of polymerizable ionic liquids and the resulting obtainment of exfoliated nanocomposites is reported. The exfoliation was achieved using three different ionic liquids structurally bearing a vinyl group: 1-methyl-3-(4 vinylbenzyl)imidazolium chloride salt (IL_1), 1-methyl-1-(4 vinylbenzyl)pyrrolidinium chloride (IL_2), and 1-methyl-3-vinyl imidazolium iodide (IL_3) and a urea-kaolinite intercalate as precursor. The reaction was done in one step by an in situ polymerization-exfoliation process. (13)C CP/MAS NMR spectra confirmed the spontaneous polymerization of the ionic liquid during the exfoliation process to afford atactic polystyrene derivatives in the case of IL_1 and IL_2. The amount of organic material in the exfoliated nanocomposite was close to 30% as shown by thermal gravimetric analysis. This amount is small in comparison to the amount obtained when the exfoliation was done using sodium polyacrylate (Letaief and Detellier, Langmuir2009, 25, 10975). XRD as well as SEM analysis confirmed a total exfoliation of the kaolinite when the reaction was done using urea kaolinite, whereas a microcomposite, made predominantly of kaolinite platelet aggregates dispersed in the polymeric matrix, was formed when dimethylsulfoxide kaolinite was used as the precursor. PMID- 22073926 TI - Orientational and motional narrowing of solid-state NMR lineshapes of uniaxially aligned membrane proteins. AB - A unified theory for the NMR line shapes of aligned membrane proteins arising from uniaxial disorder (mosaic spread) and global rotational diffusion about the director axis is presented. A superoperator formalism allows one to take into account the effects of continuous radiofrequency irradiation and frequency offsets in the presence of dynamics. A general method based on the Stochastic Liouville Equation makes it possible to bridge the static and dynamic limits in a single model. Simulations of solid-state NMR spectra are performed for a uniform alpha helix by considering orientational disorder and diffusion of the helix as a whole relative to the alignment axis. The motional narrowing of the resonance lines is highly inhomogeneous and can be used as an additional angular restraint in structure calculations. Experimental solid-state NMR spectra of Pf1 coat protein support the conclusions of the theory for two limiting cases. The static disorder dominates the (15)N NMR spectra of Pf1 aligned on a phage, while fast uniaxial diffusion provides a line narrowing mechanism for the Pf1 protein reconstituted in magnetically aligned bicelles. PMID- 22073927 TI - Use of the Internet by parents of middle school students: internet rules, risky behaviours and online concerns. AB - Using the Internet is a daily occurrence for parents and children in today's world. Although they use the Internet differently, many individuals may face online hazards that they may be ill equipped to deal with. To better understand Internet use and online behaviours, a study was conducted with 227 parents of early adolescent (ages 11 to 14 years) middle school students (grades 6, 7 and 8). Four important findings emerged: (1) parents are using the Internet like their children but have different online behaviours; (2) parents have Internet use rules at home; (3) parents are participating in risky Internet behaviours (electronic aggression, intentional online harassment and communication with online strangers); and (4) parents are concerned about their child's online safety, specifically about the exposure to sexually explicit materials and online strangers, but the majority of parents do not know where to report negative or unsafe Internet experiences. Nurses, clinicians, healthcare providers and other professionals can and do provide comprehensive care to families by identifying needs and areas of knowledge deficit. By asking Internet use questions, nurses and other professionals are able to develop plans of care for all family members that will promote Internet safety and healthy lifestyle choices. PMID- 22073928 TI - 'Your good days and your bad days' an exploration and consideration of how lay people conceptualize depression. AB - Depression remains a significant public health issue globally; 121 million people are affected by depression health education campaigns. Regardless of the prevalence of depression and recent health education campaigns to reduce the burden of depression, many people are still stigmatized and sometimes excluded from the society in which they live. Using qualitative research, the aim of this study was to explore lay people's perceptions and attitudes of mental disorder and in particular depression. A purposive sample of 22 lay people were each asked to read a case scenario which was then followed up by the researcher using open ended questions to explore their knowledge and attitudes and beliefs relating to depression. The data was analysed using Braun & Clarke's strategy of thematic analysis. The results revealed that many of the participants were familiar with the concept of depression, either through their own experiences of the disorder or through knowing people with depression. The participants also drew from psychosocial explanations of depression and located depression as part of the human condition. The paper suggests that lay people's concepts of depression offer rich complex and diverse perspectives that enhance professional views and may lead to a greater understanding of uptake and acceptance of care for depression. PMID- 22073929 TI - Unilateral auditory neuropathy spectrum disorder. AB - CONCLUSIONS: The majority of the patients with unilateral auditory neuropathy spectrum disorder (UANSD) were pediatric and mostly showed a great degree of hearing loss when diagnosed. Abnormal auditory brainstem response (ABR) and preserved otoacoustic emissions (OAEs) and/or cochlear microphonics (CM) were important features to differentiate it from common sensorineural deafness and central nerve hearing loss. OBJECTIVE: To identify the clinical characteristics of patients with UANSD. METHODS: This was a retrospective study involving 14 patients diagnosed as having UANSD between 2004 and 2010 in the Chinese PLA Hospital. RESULTS: In all, 50% of the cases were males (1:1 sex ratio) and the average age of onset was 4.1 years. Of the 14 affected ears with UANSD in these cases, 6 were left-sided, while 8 were right-sided. Of the 14 contralateral ears, 4 presented with sensorineural hearing loss, while the other 10 showed normal hearing. The degree of hearing loss in the 14 affected ears varied, including moderate in 1, moderately severe in 4, severe in 5, and profound in 4. ABRs were absent in the 14 affected ears, while the OAEs, and/or CM were present. PMID- 22073930 TI - Peripheral blood immunologic phenotype of population-based breast cancer cases and matched controls. PMID- 22073931 TI - Synergistic co-entrapment and triggered release in hollow nanocapsules with uniform nanopores. AB - We describe a new co-entrapment and release motif based on the combination of noncovalent and steric interactions in materials with well-defined nanopores. Individual components enter hollow nanocapsules through nanopores in the capsule shell. Their complex, larger than the pore size, remains entrapped. The dissociation of the complex upon external stimulus releases entrapped components. Reversible formation of complexes between diaza-18-crown-6 and metal ions was used to demonstrate the feasibility of new approach to co-entrapment and triggered release. PMID- 22073932 TI - An accuracy assessment of forensic computerized facial reconstruction employing cone-beam computed tomography from live subjects. AB - The utilization of 3D computerized systems has allowed more effective procedures for forensic facial reconstruction. Three 3D computerized facial reconstructions were produced using skull models from live adult Korean subjects to assess facial morphology prediction accuracy. The 3D skeletal and facial data were recorded from the subjects in an upright position using a cone-beam CT scanner. Shell-to shell deviation maps were created using 3D surface comparison software, and the deviation errors between the reconstructed and target faces were measured. Results showed that 54%, 65%, and 77% of the three facial reconstruction surfaces had <2.5 mm of error when compared to the relevant target face. The average error for each reconstruction was -0.46 mm (SD = 2.81) for A, -0.31 mm (SD = 2.40) for B, and -0.49 mm (SD = 2.16) for C. The facial features of the reconstructions demonstrated good levels of accuracy compared to the target faces. PMID- 22073933 TI - Core management principles in rheumatoid arthritis to help guide managed care professionals. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that affects approximately 1% of the population. Initial symptoms include joint swelling, stiffness, and tenderness, which are all causes of disability. The diagnosis of RA is based on patient history of joint pain and stiffness, the documentation of symmetric polyarticular joint synovitis, and laboratory measures including radiographs, inflammatory markers, and autoantibodies. As the disease progresses, synovial inflammation leads to cartilage damage, bone erosions, and joint destruction, the major causes of long term disability. RA is associated with many comorbidities and complications, including cardiovascular disease, which is responsible for higher rates of mortality among patients compared with the general population. Over the past 2 decades, advances in the development of synthetic disease-modifying antirheumatic drugs (DMARDs) and biologic agents for RA have markedly changed treatment goals and management strategies. OBJECTIVES: To review recent updates in the diagnosis and treatment of RA, as well as the importance of early and aggressive treatment and management strategies. SUMMARY: Borrowing from other medical fields, a paradigm of "tight control" of RA has been supported by evidence and is gaining wide acceptance in rheumatology. In 2010, the American College of Rheumatology and the European League Against Rheumatism (EULAR) published revised classification criteria for RA, which will assist in the diagnosis of early RA and facilitate appropriate treatment intervention. Over the last decade, many patients on biologic agents have demonstrated that early and aggressive treatment of RA is beneficial in treating synovial inflammation, delaying joint damage, and improving patient outcomes. Contemporary management strategies based on early diagnosis, aggressive treatment, and regular monitoring have helped a significant number of patients with RA achieve current treatment goals of low levels of disease activity and, in some cases, clinical remission. PMID- 22073934 TI - Assessment of disease activity and treatment outcomes in rheumatoid arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease which primarily causes a symmetric polyarthritis. Clinical manifestations of the disease include joint pain, stiffness, and swelling. Unless treated, this debilitating disease can progress into long-term disability. Medications for RA include synthetic disease-modifying antirheumatic drugs (DMARDs) and biologic agents. The rapid expansion of new RA drugs into the market has led to a need for health care practitioners to understand the effectiveness of each medication and the indications of use including when to initiate and stop therapies. Clinical assessment tools, including biomarkers used to indicate RA and the progression of the disease, have been proven effective for making a diagnosis and determining effective treatment regimens. Disease activity scales are also useful for guiding diagnoses and monitoring patients to assess treatment effectiveness. OBJECTIVES: To review the various clinical assessment tools that have been designed to confirm an early diagnosis of RA, measure disease progression, and assist in determining the most optimal treatment regimens for patients with RA. SUMMARY: The diagnosis of RA combines the patient history of joint pain and stiffness and the physical examination documentation of symmetric polyarticular joint swelling (synovitis). Laboratory tests including radiographs and blood tests for biomarkers can provide useful information to confirm the diagnosis of RA. Various autoantibodies have been reported in the blood of RA patients, but only the rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti CCP) have been incorporated as diagnostic measures in routine clinical practice. Monitoring and assessment instruments for RA include the Disease Activity Score 28 (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Although these clinical assessment tools have limitations, health care providers can use them as measures of disease progression and to assist in planning treatment strategies to modify disease activity and improve the quality of life for the patient. PMID- 22073935 TI - Biologic agents in rheumatoid arthritis: an update for managed care professionals. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory arthritis that clinically manifests as joint pain, stiffness, and swelling. If left untreated, persistent synovial inflammation can progress to cartilage and bone destruction and ultimately to major long-term disability and mortality. Synthetic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, leflunomide, and sulfasalazine, have markedly improved clinical symptoms and slowed joint damage in RA patients. However, despite the effectiveness of synthetic DMARDs, many patients who use them continue to have clinical symptoms of inflammation and progressive joint destruction. Recent advances in our understanding of the pathogenesis of RA have led to the identification of novel cellular and molecular therapeutic targets. Biologic agents aimed at these targets have provided some evidence of effectiveness that is transforming the management of RA. OBJECTIVE: To inform health care providers about some of the recent advances in RA pathogenesis and innovative biologic therapies that have shown effectiveness in improving clinical outcomes and inhibiting radiographic progression. SUMMARY: Although the specific trigger of the autoimmune response in RA is not known, pathogenesis is generally believed to be associated with the generation of autoantibodies through interactions of antigen-presenting cells with the adaptive immune system (CD4 + T cells and B cells). The main inflammatory mediators of joint inflammation and destruction in RA are tumor necrosis factor (TNF)-alpha, interleukin-1 (IL-1), IL-6, chemokines, and proteases. Advances in our understanding of the key cells and inflammatory cytokines have led to the development of targeted biologic agents. As of 2011, 5 TNF-alpha inhibitors are approved for use by the FDA: infliximab, etanercept, adalimumab, golimumab, and certolizumab pegol. In randomized clinical trials, all of these agents have been shown to be effective in reducing clinical signs of inflammation in RA patients who have failed synthetic DMARDs. Multiple studies have demonstrated significant benefits of early treatment with TNF-alpha inhibitors combined with methotrexate. Other FDA-approved biologic agents for treating moderate-to-severe RA include abatacept, rituximab, and tocilizumab. All biologic agents carry an increased risk of infections. Additional potential side effects include infusion and injection site reactions for intravenous and subcutaneously administered agents, respectively. All patients being considered for biologic agents should be screened annually for tuberculosis and should receive pneumococcal, influenza, and hepatitis B vaccinations. PMID- 22073936 TI - Comparative effectiveness research (CER): a summary of AHRQ's CER on therapies for rheumatoid arthritis. AB - BACKGROUND: In recent years, the U.S. government has designated funding of several large-scale initiatives for comparative effectiveness research (CER) in health care. The American Recovery and Reinvestment Act (ARRA) of 2009 apportioned more than $1 billion to support CER programs administered by the Department of Health and Human Services (DHHS), the National Institutes of Health (NIH), and the Agency for Healthcare Research and Quality (AHRQ). CER is generally defined as the undertaking of original research or systematic reviews of published literature in order to compare the benefits and risks of different approaches to preventing, diagnosing, or treating diseases. These approaches may include diagnostic tests, medications, medical devices, and surgeries. The overall goals of CER are to support informed health care decisions by patients, clinicians, payers, and policy makers and to apply its evidence to ultimately improve the quality, effectiveness, and efficiency of health care. OBJECTIVES: To (a) provide managed care professionals with general definitions of CER, specifically as it is administered by AHRQ; (b) discuss the importance of CER to clinical and managed care pharmacists; and (c) summarize key methods and findings from AHRQ's 2007 comparative effectiveness review on therapies for rheumatoid arthritis (RA). SUMMARY: As supported by AHRQ, CER is conducted in order to synthesize comprehensive evidence on the comparative benefits and harms of treatment interventions. The findings from comparative effectiveness reviews can thus contribute to informing therapeutic strategies and treatment decisions. In 2007, a multitude of RA treatment options and studies motivated AHRQ to commission a systematic comparative effectiveness review. Conducted by investigators at the RTI-University of North Carolina Evidence-Based Practice Center, the review included comparisons of synthetic disease-modifying antirheumatic drugs (DMARDs), biologic agents, synthetic DMARDs versus biologic agents, and various combination therapies. Head-to-head comparisons of synthetic DMARDs generally revealed no significant differences in long-term clinical and radiographic outcomes, or in functional capacity or health-related quality of life. Two nonrandomized prospective cohort studies and 1 open-label effectiveness trial reported no differences in ACR20 and ACR50 response rates in patients treated with the tissue necrosis factor (TNF)-alpha inhibitors etanercept and infliximab. Comparisons of TNF-alpha inhibitors generally indicated no significant differences in rates of adverse events, including serious infections, and no increases in rates over time. In comparisons of a biologic agent combined with methotrexate versus a biologic agent alone, combination therapies were generally associated with better clinical response rates and better outcomes of functional capacity and quality of life. The most common adverse events observed in studies on biologic agents were diarrhea, headache, nausea, rhinitis, injection site reactions, and upper respiratory tract infections. PMID- 22073937 TI - Potential advantages of interprofessional care in rheumatoid arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) affects over 1 million people in the United States. Although the emergence of new medications has substantially improved treatment options and outcomes for patients with RA, the disease is still a major cause of morbidity and mortality. In addition, significant barriers to adherence characterize RA medication management. A reasonable approach to improving RA patient outcomes entails interprofessional, multidisciplinary models of care. Working with rheumatology specialists, RA multidisciplinary care teams may comprise case managers, pharmacists, physical and occupational therapists, social workers, physiatrists, orthopedists, or other health professionals. Experience and evidence have supported the value of interprofessional, coordinated care models for patients with various chronic diseases. However, potential drawbacks include the costs associated with implementation of such approaches, the extra time required for their administration, and the lack of incentives for clinicians to adopt collaborative care approaches. OBJECTIVES: To summarize the arguments and evidence for interprofessional, multidisciplinary care programs in RA. SUMMARY: Various multidisciplinary models of RA care have been described in the literature. Whereas the case for implementing such models is underscored by the chronic nature of the disease, by its comorbidities and complications, and by barriers to patient medication adherence, cost-effectiveness analyses to document benefits of coordinated interprofessional RA care are lacking. Most studies on interprofessional care in RA are relatively old and have been conducted outside of the United States. Nonetheless, the findings are still relevant and may shed light on potential avenues for the development of new models in this country. PMID- 22073939 TI - Minimally important clinical difference of the Timed 25-Foot Walk Test: results from a randomized controlled trial in patients with multiple sclerosis. AB - BACKGROUND: Limited data define what constitutes a clinically significant change on the Timed 25-Foot Walk (T25FW) in multiple sclerosis (MS); however, most studies suggest a value of >=20%. Analyses were undertaken to estimate the minimally important clinical difference (MICD) in walking speed as measured by the T25FW in patients with MS. METHODS: Data from MS-F203, a randomized trial of dalfampridine extended release tablets, 10 mg twice daily (prolonged release/sustained-release fampridine outside the US) in patients with MS, were used to calculate the MICD, as an absolute and percentage value, for the T25FW test. Both anchor- (using the Clinician Global Impression [CGI]) and distribution based (2.77 * standard error of measurement or 0.50 standard deviation units) approaches were used. Using the anchor-based estimations, the proportion of patients in the dalfampridine and placebo groups achieving at least a MICD in MS F203 was determined. RESULTS: A correlation between change in T25FW speed during and CGI at the end of double-blind period was found (Spearman r = -0.39, p < 0.0001). Irrespective of treatment group, participants categorized 'minimally improved' by the CGI had a mean improvement in T25FW speed of 0.36 feet/second or a 17.2% relative change from an average baseline walking speed of 2.1 feet/second (effect size = 0.49); values representing MICDs. MICD estimates of 0.35 and 0.37 feet/second were generated using distribution-based approaches. In MS-F203, a greater proportion of patients receiving dalfampridine achieved >=0.36 feet/second (12/72 vs. 78/224, p = 0.007) and a 17.2% (11/72 vs. 87/224, p = 0.0005) improvement in T25FW speed compared to placebo. LIMITATIONS: MICD estimates from this analysis may not apply to patients with different disease characteristics from MS-F203. A different anchor may result in a different MICD estimation. CONCLUSION: Our MICD estimate for an improvement in T25FW is close to previous estimates of 20% change. Dalfampridine may improve walking speed in a considerable proportion of patients by a clinically relevant amount. PMID- 22073938 TI - Shear bond strength between Ni-Cr alloy bonded to a ceramic substrate. AB - INTRODUCTION: The aim of this study was to evaluate the shear bond strength between a Ni-Cr alloy and a ceramic system submitted or not to thermocycling. MATERIALS AND METHODS: Forty-eight cylinder blocks of Ni-Cr with 3.0 mm diameter by 4.0 mm hight and 48 disc-shaped specimens (7.0 mm in diameter by 2.0 mm thick) composed of ceramic were prepared. The Ni-Cr cylinder blocks were randomised in two groups of 24 specimens each. One group was submitted to air-particle abrasion (sandblasting) with 50 MUm Al(2)O(3) (0.4-0.7 MPa) during 20 s, and the other group was submitted to mechanical retentions with carbide burrs. Each group was subdivided into other two groups (n = 12), submitted or not to thermocycling (500 cycles, 5-55 degrees C). The cylinder blocks were bonded to the disc-shaped ceramic specimens under 10 N of load. The shear bond strengths (MPa) were measured using a universal testing machine at a cross head speed of 0.5 mm/min and 200 kgf of load. The data were submitted to statistical analysis (anova and Tukey's test). RESULTS: The air-particle abrasion group exhibited significantly higher shear bond strength when compared to drilled group (p < 0.05). CONCLUSIONS: Thermocycling decreased significantly the bond strengths for all groups tested. PMID- 22073940 TI - Web-browser encryption of personal health information. AB - BACKGROUND: Electronic health records provide access to an unprecedented amount of clinical data for research that can accelerate the development of effective medical practices. However it is important to protect patient confidentiality, as many medical conditions are stigmatized and disclosure could result in personal and/or financial loss. RESULTS: We describe a system for remote data entry that allows the data that would identify the patient to be encrypted in the web browser of the person entering the data. These data cannot be decrypted on the server by the staff at the data center but can be decrypted by the person entering the data or their delegate. We developed this system to solve a problem that arose in the context of clinical research, but it is applicable in a range of situations where sensitive information is stored and updated in a database and it is necessary to ensure that it cannot be viewed by any except those intentionally given access. CONCLUSION: By developing this system, we are able to centralize the collection of some patient data while minimizing the risk that protected health information be made available to study personnel who are not authorized to use it. PMID- 22073942 TI - Regions identity between the genome of vertebrates and non-retroviral families of insect viruses. AB - BACKGROUND: The scope of our understanding of the evolutionary history between viruses and animals is limited. The fact that the recent availability of many complete insect virus genomes and vertebrate genomes as well as the ability to screen these sequences makes it possible to gain a new perspective insight into the evolutionary interaction between insect viruses and vertebrates. This study is to determine the possibility of existence of sequence identity between the genomes of insect viruses and vertebrates, attempt to explain this phenomenon in term of genetic mobile element, and try to investigate the evolutionary relationship between these short regions of identity among these species. RESULTS: Some of studied insect viruses contain variable numbers of short regions of sequence identity to the genomes of vertebrate with nucleotide sequence length from 28 bp to 124 bp. They are found to locate in multiple sites of the vertebrate genomes. The ontology of animal genes with identical regions involves in several processes including chromatin remodeling, regulation of apoptosis, signaling pathway, nerve system development and some enzyme-like catalysis. Phylogenetic analysis reveals that at least some short regions of sequence identity in the genomes of vertebrate are derived the ancestral of insect viruses. CONCLUSION: Short regions of sequence identity were found in the vertebrates and insect viruses. These sequences played an important role not only in the long-term evolution of vertebrates, but also in promotion of insect virus. This typical win-win strategy may come from natural selection. PMID- 22073941 TI - Vasovagal reactions in whole blood donors at three REDS-II blood centers in Brazil. AB - BACKGROUND: In Brazil little is known about adverse reactions during donation and the donor characteristics that may be associated with such events. Donors are offered snacks and fluids before donating and are required to consume a light meal after donation. For these reasons the frequency of reactions may be different than those observed in other countries. STUDY DESIGN AND METHODS: A cross-sectional study was conducted of eligible whole blood donors at three large blood centers located in Brazil between July 2007 and December 2009. Vasovagal reactions (VVRs) along with donor demographic and biometric data were collected. Reactions were defined as any presyncopal or syncopal event during the donation process. Multivariable logistic regression was performed to identify predictors of VVRs. RESULTS: Of 724,861 donor presentations, 16,129 (2.2%) VVRs were recorded. Rates varied substantially between the three centers: 53, 290, and 381 per 10,000 donations in Recife, Sao Paulo, and Belo Horizonte, respectively. Although the reaction rates varied, the donor characteristics associated with VVRs were similar (younger age [18-29 years], replacement donors, first-time donors, low estimated blood volume [EBV]). In multivariable analysis controlling for differences between the donor populations in each city younger age, first time donor status, and lower EBV were the factors most associated with reactions. CONCLUSION: Factors associated with VVRs in other locations are also evident in Brazil. The difference in VVR rates between the three centers might be due to different procedures for identifying and reporting the reactions. Potential interventions to reduce the risk of reactions in Brazil should be considered. PMID- 22073944 TI - Where to go? PMID- 22073943 TI - The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation. AB - BACKGROUND: This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines. METHODS: Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 ? groups (control, colitis, HFD and colitis + HFD). RESULTS: Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group. CONCLUSION: Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream. PMID- 22073946 TI - Survival role of superoxide dismutase 1 on human granulosa luteinized cells in vitro. AB - OBJECTIVE: Deleterious effects of free radicals do not only result from the amount of free radicals produced but also are related to the efficiency and to the activities of enzymatic antioxidant systems. We investigated the effect of exogenous superoxide dismutase (SOD1) or Cu-chelating agent diethyldithiocarbamate (DDC) on the apoptosis (caspase-3 activity) of human granulosa luteinized cells (hGLC) in vitro. METHODS: The effects of SOD1 and DDC were studied using in vitro culture system, caspase-3 and the total SOD activity in hGLCs were measured using AcDEVD-PNA substrate and Beaushap and Fridovich methods, respectively, after 48 h of the culture period. RESULTS: The activity of SOD1 was the lowest in GLCs treated with 100 uM DDC as compared to control cells and to the cells supplemented with Cu, Zn-SOD or DDC (10 uM). The effect of DDC was associated with elevated caspase-3 activity as compared to control cells. CONCLUSIONS: It was demonstrated for the first time that the supplementation of cultured hGLCs with Cu2+, Zn2+-SOD (200 U/ml) maintains the viability of hGLCs via caspase-3 suppression. PMID- 22073948 TI - Goiter, cardiovascular and metabolic disorders in patients with acromegaly. AB - OBJECTIVE: This study evaluated the relationship between selected acromegaly complications such as IGF-1 serum concentrations at diagnosis as well as of controlled and uncontrolled disease. METHODS: A total of 113 acromegaly patients were enrolled to the study and the duration of active and uncontrolled disease was evaluated as a crucial cause of selected complications. RESULTS: Goiter, diabetes, hypercholesterolemia, hypertriglycerydemia, hypertension and ischemic heart disease were diagnosed in 85(75.2 %), 23(20.3 %), 48(51.0 %), 15(13.3 %), 65(57.5 %) and 18(15.9%) patients, respectively. Prevalence of goiter and diabetes was significantly related to the duration of uncontrolled acromegaly (p<0.01) as well as to the prevalence of hypertension and ischaemic heart disease (p0.05). After three years, there was a significant risk of an acromegaly patient being diagnosed at least with one of the above mentioned diseases (p<0.05) and such risk became more significant after four years (p0.05) related to the prevalence of the already mentioned complications. CONCLUSION: The treatment of acromegaly patients should be geared towards fulfilling all criteria for controlled disease, thereby alleviating potential complications and decreasing mortality. PMID- 22073947 TI - Iodine concentration and signs of apoptosis in the thyroid and pituitary of female rats after different single doses of potassium iodide. AB - OBJECTIVE: The aim of this work was to study the content of iodine as well as the expression of caspase 8 and caspase 32 in the thyroid and anterior pituitary in rats after a single dose of iodide. METHODS: A total of 49 inbred rat females weighing 250-300 g at the stage of diestrus and/or metestrus were used. Pituitaries and thyroids were dissected from 15 control rats and from the groups of 8 rats each given potassium iodide by gavage in doses of 1, 4, 8 and 25 MUg/100 g at 48 h before sacrifice. In two rats of each group the level of iodine in thyroids and pituitaries was estimated in terms of weight percent of iodide in dry tissue (wt % I-2/dry tissue) using the wavelength dispersive spectrometry (WDS) quantitative analysis. The expression of caspase 8 and caspase 32 in thyroids and pituitaries in terms of the percentage of positive immunostained area (% PA) was measured by streptavidin-biotin method using specific polyclonal antibodies. RESULTS; In the thyroids, iodine concentration increased after 1 MUg/100 g, but decreased after 8 and 25 MUg/100 g, while that in the pituitaries significantly increased after all doses of iodide with the peak after 8 mg/100 g. After the same iodide dose also the peak of caspase 32 and caspase 8 appeared in the pituitary. However, in the thyroid only increased caspase 32 was found together with a decrease of iodine concentration. CONCLUSION: Several interrelations between iodine in the thyroid and pituitary were found. In addition, the signs of apoptosis appeared directly related to the concentration of iodine in the pituitary, but inversely related to iodine concentration in the thyroid. PMID- 22073949 TI - Bone mineral density, pathological fractures and bisphosphonate therapy in prostate cancer patients on androgen deprivation therapy. AB - OBJECTIVES: The aim of the study is to evaluate the changes of bone mineral density (BMD), incidence of pathological fractures and to asses the effect of bisphosphonate therapy in prostate cancer patients (PCa) on androgen deprivation therapy (ADT) with the use of LHRH. METHODS: In this prospective study bone mass density (BMD) was assessed by dual x-ray absorptiometry (DXA) in 97 PCa patients and 89 patients of compared group. DXA was examined at baseline and patients in the study group were subjected to ADT. PCa patients with osteoporosis were treated by calcium, vitamin D, and bisphosphonate and the subsequent DXA was made after 10 months. All other PCa patients (non-osteoporotic) had DXA examined every 12-14 months. RESULTS: Patients of the study group had significantly lower baseline L1-L4 and total hip BMD (p=0.028, p=0.022). BMD was significantly lower in L1-L4 and total hip (p=0.004, p<0.001, resp.) after 10-14 months and in L1-L4, femoral neck, and total hip (p=0.001, p=0.037, p< 0.001, resp.) after 20-26 months of ADT. After the treatment for osteoporosis with bisphosphonate a significant increase of BMD (p=0.04) was found in a total of 23 patients. Overall, the incidence of fractures after 20-26 months of ADT was 8.5 %. CONCLUSIONS: Osteopenia is very common in hormone naive PCa patients. There was a significant loss of BMD after 12 months of ADT which was progressive while the patients were on ADT. Bisphosphonate therapy was effective after 20 months of treatment. The incidence of pathological fractures was 7-fold higher in the study group. PMID- 22073950 TI - Mixed gonadal dysgenesis: whole life follow-up of a rare case. AB - There are two forms of gonadal dysgenesis - mixed and pure. In the mixed form, some differentiated gonads as well as some either ovarian or testicular rudiments are present. This form results in a number of phenotypes with a possibility of malignant transformation. In the pure form occurring in female gender, also some rudimental gonads are bilaterally present. In the case of simultaneous presence of Y chromosome, also some malignant transformation may appear (Siklar et al. 2007). Chromosomal aberrations are present in 2-7 % adult pairs with fertility disorders and in 0.6 % of newborns. However, only few cases with similar chromosomal aberrations were described so far (Roubin et al. 1977; Alexander et al. 1978; Teyssier et al. 1982; Caglayan et al. 2009). Mixed gonadal dysgenesis presents as a unilateral testis, usually intraabdominal, also with a streak gonad on contralateral side, and persistent mullerian structures. 45X/45XY karyotype is the most frequent in such cases with predominance of 45X cells in both peripheral lymphocytes and gonads. We present a rare case of a left undescended testis, normally descended right testis, with penoscrotal hypospadias, who had a normal karyotype and whose histopathological findings were endometrial tissue and fallopian tube in left testicular biopsy. Gonadal dysgenesis should always be kept in mind because of a possibility of undescended testis and proximal hypospadias. If karyotype reveals a 46XY gonadal dysgenesis, these patients need the careful follow-up to screen for gonadoblastoma in remaining normal testis. Subjecting the patients to prophylactic orchidectomy with hormone replacement can be an additional option in such patients. PMID- 22073951 TI - Pathogenesis of Graves' disease focusing on Graves' ophthalmopathy. PMID- 22073952 TI - The effect of income on fertility. AB - Abstract Cross-sectional data and long-period time series data have generally shown an inverse relationship between income and fertility. But short-period time series data over the business cycle have shown a direct relationship. The first part of this paper resolves this apparent paradox by showing that it arises from a statistical illusion-specification bias due to omitted lagged variables. The second part of the paper then considers the likely unconditional effect of income on fertility in several sorts of situations: (a) secular income increase in less developed countries; (b) cyclical income change in industrialized countries; (c) secular income increase in industrialized countries; and (d) incentive payments for higher and lower fertility. PMID- 22073953 TI - The role of sterilization in controlling Puerto Rican fertility. AB - Abstract This paper provides evidence that the prevalence of female sterilization in Puerto Rica has increased substantially in recent years. It is estimated that about one-third of all Puerto Rican mothers aged 20 to 49 in 1965 were sterilized. This estimate is based on data from an island-wide survey in 1965 (Master Sample Survey of Health and Welfare). Additional data from this and other sources are analysed, leading to the conclusion that sterilization, rather than any other means of fertility control, was largely responsible for the decline in Puerto Rican fertility since 1950. PMID- 22073954 TI - Rural-urban fertility differentials in Western Nigeria. AB - Abstract The paper attempts to glean some information on differential fertility from data obtained in a survey of selected urban and rural communities in Western Nigeria. The results show that the attitudes of rural women are far more favourable to high fertility than those of urban women, though for both groups the modal number of children preferred is five or six. The analysis also yields a total fertility of nearly six and an average family size of about five for both groups. No conclusive evidence of rural-urban fertility differentials has, however, been found. All that can be said on the basis of the available data is that the level of fertility in Western Nigeria is currently very high and that urban fertility is probably as high as rural fertility, though the probability of much larger errors in the rural than in the urban data may imply somewhat higher rural fertility. PMID- 22073955 TI - Sample registration in India. AB - Abstract The Sample Registration Project in India is designed to obtain current estimates of birth and death rates for the whole country. It is being implemented quite rapidly. Rural and urban areas in all states and Union Territories in India will be covered before the close of 1969. Bigger states have 150 sample units in rural areas and 60 to 100 units in urban areas. Essential elements of the project for each unit are: (1) continuous enumeration of births and deaths in respect of usual resident population by a paid part-time local enumerator; (2) a six-month household survey to detect births and deaths which occurred to the usual resident population during the previous six months; and (3) manual matching of all event from enumeration and surveys and field re-check of unmatched events to obtain the 'best' count of real number of events. The results of a full scale sample in four states and pilot sample in ten states indicate that the crude birth and death rates are around 40 and 18 per 1,000, respectively, for India's rural population. Most of the problems of implementation are operational or administrative rather than statistical. The main problem in the whole project is to maintain control of field operations well enough at each stage to ensure that prescribed instructions and methodology are being followed; particularly in the six-month survey. Experience in India indicates that sample registration techniques are capable of providing reliable birth and death rates in similar conditions in developing countries. However, there are still a number of methodological problems which must be tested as the sample registration evolves. PMID- 22073956 TI - Some results from asian population growth studies. AB - Abstract Coverage estimates of births and deaths derived from the matching experience of a relatively comprehensive group of studies conducted in Asia and employing dual collection systems are resented and analysed. Major conclusions based on these Asian studies include: (1) coverage of live births has generally been more complete than that for deaths; (2) nevertheless, unadjusted rates of natural increase tend to be underestimates; (3) there is great variability within each type of collection system in the coverage rates observed; and (4) one-time household surveys, as a group, seem to be particularly subject to underreporting of vital events. PMID- 22073957 TI - A study of cohort life cycles: Cohorts of native born Massachusetts women, 1830 1920. AB - Abstract This paper expands the conceptual apparatus offamily life cycle analysis and illustrates its usefulness by applying it to a population. There is a normatively sanctioned life cycle that a female born into American society is expected to follow as she moves from birth to death: she is expected to survive through childhood, marry, bear and rear children, and survive jointly with her husband until her children leave the home. Paul Glick, in several articles, has calculated mean ages at which these various events are experienced. The life cycle analysis proposed here, however, focuses on the distribution of women according to type of life cycle experienced. Starting with a cohort of 100,000 females, six alternative life cycle possibilities are differentiated and the number who follow each of the types is calculated. The six types are: (1) abbreviated, the female dies before she is exposed to the risk of marriage; (2) spinster, the woman is exposed to the risk of marriage but does not marry; (3) barren, the woman marries but remains childless; (4) dying mother, the woman has children but dies before the last one leaves home; (5) widowed mother, the woman has children and survives until they leave home, but her husband dies before that event; and (6) typical, the woman marries, has children, and survives jointly with her husband until the last one leaves home. Applying this approach to several cohorts of native-born Massachusetts women born at different times some striking changes appear. For example, the number of women from a birth cohort of 100,000 who follow the typical life cycle increases from 21,000 for the cohort born in 1830 to 57,000 for the cohort born in 1920. The demographic, social and economic implications of a change of this magnitude are of considerable consequence. PMID- 22073958 TI - Pregnancy outcome and the time required for next conception. AB - Abstract Variations in the time required for next conception by outcome ofthe preceding pregnancy, and the age of woman, are studied for Taiwanese women. Pregnancy interval, defined as the period between the end of one pregnancy and the beginning of the next, is taken as a measure of the time required for the next conception. The averages and variances of pregnancy intervals are estimated from reports of pregnancies occurring in a probability sample of 2,443 married women, aged 20-39, living in Taichung (Taiwan) in 1962. The effects of 'truncation bias' and 'memory bias' on the two moments of pregnancy intervals are estimated indirectly by cross-classifying women according to their ages at interview and their ages at the beginning (or end) of each pregnancy interval. The moments of post-partum amenorrhoea are, then, estimated indirectly from the moments of pregnancy intervals. The effects of truncation bias and memory bias are compensatory in this sample. In the absence of contraception, women, on an average, took longer to conceive following a live birth than following a foetal death. The time taken for next conception increases as women become older irrespective of the outcome of the preceding pregnancy. PMID- 22073959 TI - Probability of marriage and fertility of women suffering from schizophrenia or affective disorders. AB - Abstract Schizophrenia and affective disorders are the main forms of severe mental illness among women of childbearing age; earlier this century European and American studies showed that the fertility of these patients was reduced. Since the second world war the development of community-orientated psychiatry appears to have resulted in a lessening of differentials between patients and normal women. The present study was designed to estimate probability of marriage and fertility of such patients in London followingthese developments in psychiatry. Over 1,000women aged 16-50 were selected from 1955-63 admissions to a London hospital, and data were collected from medical records. Owing to the demographic heterogeneity of the sample, the analysis of maximum discriminative power was to compare each patient with a normal woman of corresponding age, observed during identical calendar periods, as derived from Registrar General's estimates. The fertility of each patient was compared with that of a normal woman, controlled for age at and duration of marriage, and an assessment was made of the effect of hospital stay on fertility. Before admission, probability of marriage of schizophrenics was just under three-quarters of that of normal women, and after admission this was greatly reduced to just over one-third of normal; women with affective disorders were very similar to normal women as regards probability of marriage, and also fertility. The fertility of schizophrenics was reduced both before and after admission, and much of the latter reduction depended on the effect of hospital stay; however, this fertility differential was too small to be clinically or socially important. The relevance of these results to the population genetics of schizophrenia is noted. Affective disorders are primarily disorders of mood, usually involving a depression, but in a smaller group of patients periods of excitement or elation involving marked overactivity of thought and behaviour. The patient may return to normal between these periods of illness, and although delusions and hallucinations sometimes occur they are usually less prominent than in schizophrenia. Affective disorders generally become evident later in life than schizophrenia, and they often require shorter periods of in-patient treatment, and the medical prognosis is often more hopeful. The expectation of affective psychoses (the most severe forms of the disorder) for a member of the general population varies between 0.3 and 1% from country to country. Milder conditions have also been included in this study, and the expectation of all these affective disorders is likely to be much higher. PMID- 22073960 TI - The risk of conception on different days of the menstrual cycle. AB - Abstract Data on 1898 menstrual cycles, for 241 married women, were analysed by means of a quantal regression programme. The locations of the day of ovulation was determined by the basal body temperature method. Estimates were obtained of the risk of conception from an act of coitus on each day, as measured from the day of ovulation. The relationship between fecundability and coital frequency was also examined. PMID- 22073961 TI - A growth model with population as an endogenous variable. AB - Abstract This paper presents a recursive model of economic growth in which particular attention is paid to the demographic assumptions and their effects on the growth of income per head. The labour inputs depend both on the growth of the labour force and on the effectiveness of labour supplied, which in turn depends on the level of consumption per head, given the stock of capital and natural resources. Population growth is a function of two types of birth control programme; one is the subsidized supply of birth control instruments and the other is a bonus scheme which pays people not to have children. In examining the solution of the model, emphasis is placed on the sensitivity of the growth rate to variations in the allocation of the state's budget among various growth and non-growth inducing expenditures, including birth control. A numerical simulation, based on South Asian data, indicates the kind of calculation that can be made in this type offully recursive model. PMID- 22073964 TI - Anti-tumour activity of 4-(4-fluorophenyl)amino-5,6,7-trimethoxyquinazoline against tumour cells in vitro. AB - In order to create novel, potent and selective anti-cancer agents, the action of 4-(4-fluorophenyl)amino-5,6,7-trimethoxyquinazoline (compound 1018) on 10 different kinds of tumour cells were assayed by MTT [3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-2H-tetrazolium bromide]. It possesses a broad spectrum of anti cancer activity. The mechanism of action of 4-(4-fluorophenyl)amino-5,6,7 trimethoxyquinazoline (hereafter referred to as compound 1018) against tumour cells was studied in androgen-independent prostate cancer PC-3 cells by microscopic observation, LDH (lactate dehydrogenase) release assay and Western blotting. Its activity was dose-dependent, with an IC50 of 13.0+/-1.4 MUM after 72 h treatment. Microscopy and LDH release assay indicated that the effect was through anti-proliferation rather than cytotoxicity. Western blot analysis also showed that treatment of cells with 50 MUM compound 1018 for 30 min almost completely inhibited EGF (epidermal growth factor)-induced phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2), which suggests that its anti proliferative effect is largely associated due to ERK1/2 activation being inhibited. Thus compound 1018 is a potential anti-cancer agent. PMID- 22073966 TI - Simulating anisotropic droplet shapes on chemically striped patterned surfaces. AB - The equilibrium shape of droplets on surfaces, functionalized with stripes of alternating wettability, have been investigated using simulations employing a finite element method. Experiments show that a droplet deposited on a surface with relatively narrow hydrophobic stripes compared to the hydrophilic stripes adopts a strongly elongated shape. The aspect ratio, the length of the droplet divided by the width, decreases toward unity when a droplet is deposited on a surface with relatively narrow hydrophilic stripes. The aspect ratio and the contact angle parallel to the stripes show unique scaling behavior as a function of the ratio between the widths of the hydrophobic and hydrophilic stripes. For a small ratio, the contact angle parallel to the stripes is low and the aspect ratio high, while for a large ratio, the contact angle parallel is high and the aspect ratio low. The simulations exhibit similar scaling behavior, both for the aspect ratio of the droplets and for the contact angles in the direction parallel to the stripes. Two liquids with different surface tensions have been investigated both experimentally and in simulations; similarities and differences between the findings are discussed. Generally, three parameters are needed to describe the droplet geometry: (i) the equilibrium contact angles on the hydrophilic and (ii) hydrophobic areas and (iii) the ratio of the widths of these chemically defined stripes. Furthermore, we derive a simple analytical expression that proves to be a good approximation in the quantitative description of the droplet aspect ratio. PMID- 22073965 TI - Base-mediated stereospecific synthesis of aryloxy and amino substituted ethyl acrylates. AB - The stereospecific synthesis of aryloxy and amino substituted E- and Z-ethyl-3 acrylates is of interest because of their potential in the polymer industry and in medicinal chemistry. During work on a copper-catalyzed cross-coupling reaction of ethyl (E)- and (Z)-3-iodoacrylates with phenols and N-heterocycles, we discovered a very simple (nonmetallic) method for the stereospecific synthesis of aryloxy and amino substituted acrylates. To study this long-standing problem on the stereoselectivity of aryloxy and amino substituted acrylates, a series of O- and N-substituted nucleophiles was allowed to react with ethyl (E)- and (Z)-3 iodoacrylates. Screening of different bases indicated that DABCO (1,4 diazabicyclo[2.2.2]octane) afforded successful conversion of ethyl (E)- and (Z)-3 iodoacrylates into aryloxy and amino substituted ethyl acrylates in a stereospecific manner. Herein are the details of this DABCO-mediated stereospecific synthesis of aryloxy and amino substituted E- or Z-acrylates. PMID- 22073967 TI - Corn mint (Mentha arvensis) extract diminishes acute Chlamydia pneumoniae infection in vitro and in vivo. AB - Corn mint ( Mentha arvensis ) provides a good source of natural phenols such as flavone glycosides and caffeic acid derivatives, which may have prophylactic properties against inflammations. This study investigated whether corn mint extract would be beneficial against a universal respiratory tract pathogen, Chlamydia pneumoniae , infection. The extract inhibited the growth of C. pneumoniae CWL-029 in vitro in a dose-dependent manner. The inhibition was confirmed against a clinical isolate K7. The phenolic composition of the extract was analyzed by UPLC-ESI/Q-TOF/MS, the main components being linarin and rosmarinic acid. These compounds were active in vitro against C. pneumoniae. Linarin completely inhibited the growth at 100 MUM. Inbred C57BL/6J mice were inoculated with C. pneumoniae K7. M. arvensis extract was given intraperitoneally once daily for 3 days prior to inoculation and continued for 10 days postinfection. The extract was able to diminish the inflammatory parameters related to C. pneumoniae infection and significantly (p = 0.019) lowered the number of C. pneumoniae genome equivalents detected by PCR at biologically relevant amounts. PMID- 22073968 TI - The paradigm of personalized therapy in oncology. AB - INTRODUCTION: Currently, anticancer therapy is mainly based on histology and on giving the same treatment to presumed homogeneous patients. The switch from histology-driven therapy to molecular clinical oncology is correlated with a better understanding of the 'molecular taxonomy' of each tumor that can provide us with targets for specific drugs. Cancer therapy is moving irreversibly towards personalized therapy that benefits selected patients. Once the potential therapeutic targets are identified, the availability of predictive biomarkers is the key element and their prospective evaluation should be a parallel component of the clinical evaluation of a new drug. AREAS COVERED: The state of the art in clinical results of personalized therapy. The authors discuss the finding that, in patients with advanced disease, a limited number of targeted agents improve overall survival, whilst the majority only have an effect on response rate and/or time to tumor progression, with efficacy limited in time due to acquired resistance. EXPERT OPINION: The mechanisms leading to resistance are related to tumor cell heterogeneity and in part explained by the cancer stem cell model and genetic instability. The steps toward the optimization of tailored therapy need validated predictive biomarkers, pharmacogenetics analysis and a close collaboration between bench and bedside. PMID- 22073969 TI - Longitudinal zipping/unzipping of self-assembled organic tubes. AB - Stimuli-responsive organic tubes are an attractive supramolecular assembly which has potential applications as a controlled release vehicle. We synthesize a smart organic tube by the coassembly of lithocholic acid (LCA) and taurolithocholic acid (TLCA) in aqueous solution. The coassembled LCA/TLCA tubes can be longitudinally unzipped into flat sheets by capillary force after being dehydrated on substrates. Consequently, the encapsulated guest molecules are released from the unzipping tubes. After the release of guest molecules, the flat sheets can be zipped back into hollow tubes upon hydration with aqueous solution. The zipping/unzipping LCA/TLCA tubes provide a new type of delivery vehicles, which may have potential for surface decontaminations. PMID- 22073970 TI - Oxazine dye-conjugated dna oligonucleotides: Forster resonance energy transfer in view of molecular dye-DNA interactions. AB - In this work, the photophysical properties of two oxazine dyes (ATTO 610 and ATTO 680) covalently attached via a C6-amino linker to the 5'-end of short single stranded as well as double-stranded DNA (ssDNA and dsDNA, respectively) of different lengths were investigated. The two oxazine dyes were chosen because of the excellent spectral overlap, the high extinction coefficients, and the high fluorescence quantum yield of ATTO 610, making them an attractive Forster resonance energy transfer (FRET) pair for bioanalytical applications in the far red spectral range. To identify possible molecular dye-DNA interactions that cause photophysical alterations, we performed a detailed spectroscopic study, including time-resolved fluorescence anisotropy and fluorescence correlation spectroscopy measurements. As an effect of the DNA conjugation, the absorption and fluorescence maxima of both dyes were bathochromically shifted and the fluorescence decay times were increased. Moreover, the absorption of conjugated ATTO 610 was spectrally broadened, and a dual fluorescence emission was observed. Steric interactions with ssDNA as well as dsDNA were found for both dyes. The dye DNA interactions were strengthened from ssDNA to dsDNA conjugates, pointing toward interactions with specific dsDNA domains (such as the top of the double helix). Although these interactions partially blocked the dye-linker rotation, a free (unhindered) rotational mobility of at least one dye facilitated the appropriate alignment of the transition dipole moments in doubly labeled ATTO 610/ATTO 680-dsDNA conjugates for the performance of successful FRET. Considering the high linker flexibility for the determination of the donor-acceptor distances, good accordance between theoretical and experimental FRET parameters was obtained. The considerably large Forster distance of ~7 nm recommends the application of this FRET pair not only for the detection of binding reactions between nucleic acids in living cells but also for monitoring interactions of larger biomolecules such as proteins. PMID- 22073972 TI - Reviews on animal diseases recently published in other journals. PMID- 22073971 TI - Erratum concerning the publication: PMID- 22073974 TI - Mindfulness and psychologic well-being: are they related to type of meditation technique practiced? PMID- 22073975 TI - Homeopathic potentization based on nanoscale domains. AB - OBJECTIVES: The objectives of this study were to present a simple descriptive and quantitative model of how high potencies in homeopathy arise. DESIGN: The model begins with the mechanochemical production of hydrogen and hydroxyl radicals from water and the electronic stabilization of the resulting nanodomains of water molecules. The life of these domains is initially limited to a few days, but may extend to years when the electromagnetic characteristic of a homeopathic agent is copied onto the domains. This information is transferred between the original agent and the nanodomains, and also between previously imprinted nanodomains and new ones. The differential equations previously used to describe these processes are replaced here by exponential expressions, corresponding to simplified model mechanisms. Magnetic stabilization is also involved, since these long-lived domains apparently require the presence of the geomagnetic field. Our model incorporates this factor in the formation of the long-lived compound. RESULTS: Numerical simulation and graphs show that the potentization mechanism can be described quantitatively by a very simplified mechanism. The omitted factors affect only the fine structure of the kinetics. Measurements of pH changes upon absorption of different electromagnetic frequencies indicate that about 400 nanodomains polymerize to form one cooperating unit. Singlet excited states of some compounds lead to dramatic changes in their hydrogen ion dissociation constant, explaining this pH effect and suggesting that homeopathic information is imprinted as higher singlet excited states. CONCLUSIONS: A simple description is provided of the process of potentization in homeopathic dilutions. With the exception of minor details, this simple model replicates the results previously obtained from a more complex model. While excited states are short lived in isolated molecules, they become long lived in nanodomains that form coherent cooperative aggregates controlled by the geomagnetic field. These domains either slowly emit biophotons or perform specific biochemical work at their target. PMID- 22073976 TI - Universal and confident phosphorylation site localization using phosphoRS. AB - An algorithm for the assignment of phosphorylation sites in peptides is described. The program uses tandem mass spectrometry data in conjunction with the respective peptide sequences to calculate site probabilities for all potential phosphorylation sites. Tandem mass spectra from synthetic phosphopeptides were used for optimization of the scoring parameters employing all commonly used fragmentation techniques. Calculation of probabilities was adapted to the different fragmentation methods and to the maximum mass deviation of the analysis. The software includes a novel approach to peak extraction, required for matching experimental data to the theoretical values of all isoforms, by defining individual peak depths for the different regions of the tandem mass spectrum. Mixtures of synthetic phosphopeptides were used to validate the program by calculation of its false localization rate versus site probability cutoff characteristic. Notably, the empirical obtained precision was higher than indicated by the applied probability cutoff. In addition, the performance of the algorithm was compared to existing approaches to site localization such as Ascore. In order to assess the practical applicability of the algorithm to large data sets, phosphopeptides from a biological sample were analyzed, localizing more than 3000 nonredundant phosphorylation sites. Finally, the results obtained for the different fragmentation methods and localization tools were compared and discussed. PMID- 22073977 TI - Guest binding dynamics with cucurbit[7]uril in the presence of cations. AB - The binding dynamics of R-(+)-2-naphthyl-1-ethylammonium cation (NpH(+)) with cucurbit[7]uril (CB[7]) was investigated. Competitive binding with Na(+) or H(3)O(+) cations enabled the reaction to be slowed down sufficiently for the kinetics to be studied by fluorescence stopped-flow experiments. The binding of two Na(+) cations to CB[7], i.e., CB[7].Na(+) (K(01) = 130 +/- 10 M(-1)) and Na(+).CB[7].Na(+) (K(02) = 21 +/- 2 M(-1)), was derived from the analysis of binding isotherms and the kinetic studies. NpH(+) binds only to free CB[7] ((1.06 +/- 0.05) * 10(7) M(-1)), and the association rate constant of (6.3 +/- 0.3) * 10(8) M(-1) s(-1) is 1 order of magnitude lower than that for a diffusion controlled process and much higher than the association rate constant previously determined for other CB[n] systems. The high equilibrium constant for the NpH(+)@CB[7] complex is a consequence of the slow dissociation rate constant of 55 s(-1). The kinetics results showed that formation of a complex between a positively charged guest with CB[n] can occur at a rate close to the diffusion controlled limit with no detection of a stable exclusion complex. PMID- 22073978 TI - The application of a violence risk assessment tool among Chinese psychiatric service users: a preliminary study. AB - The Violence Risk Screening-10 (V-RISK-10) is one of the few instruments available for evaluating violence risk among general psychiatric service users. This naturalistic prospective study involved 376 inpatients in a general psychiatric hospital in Beijing and intended to determine whether this brief instrument could be applied to a sample of Chinese consumers and whether its predictive properties could be retained. Risk assessment at admission was compared to the record of aggression and violence during the first month of hospitalization. During the research period, 108 of the 376 consumers caused 265 incidences of aggression. Receiver operating characteristics for the V-RISK-10 Chinese version yielded an area under the curve of 0.63. Its sensitivity/specificity was 0.80/0.38 and the corresponding positive/negative predictive value was 0.34/0.82. Intraclass correlation coefficient for the whole instrument was 0.89. Compared to the results of the original V-RISK-10, its predictive accuracy was lower. However, with some modification, the V-RISK-10 still shows promise as an instrument for use in daily practice in Chinese clinical settings. PMID- 22073979 TI - Visual gravitational vertical perception in peripheral vestibular hypofunction. AB - CONCLUSIONS: Rise time in the estimation of the gravitational vertical in the head tilt response (HTR) test is increased in patients with peripheral vestibular lesions and residual chronic dizziness. OBJECTIVE: Assessment of the perception of the gravitational vertical in patients with peripheral vestibular lesions through the HTR. METHODS: HTR was studied in 12 patients with peripheral vestibular lesion, 8 clinically with chronic dizziness and 4 without it; 23 normal subjects were studied as control group. Two parameters of the HTR were assessed, rise time and steady-state error to characterize a dynamical system step response. The Kolmogorov-Smirnov test (alpha = 5%) was used to verify normal distribution (steady-state error, p = 0.53; rise time, p = 0.88). The three sigma ellipse was calculated for the control group. ROC curves were used to measure the sensitivity and specificity of these parameters. RESULTS: Rise time showed increased values in peripheral vestibular lesion patients with chronic dizziness. Two-dimensional analysis (rise time vs steady-state error) allows a better discrimination between patients with peripheral vestibular hypofunction with chronic dizziness and the rest of the studied population. PMID- 22073980 TI - Derivation of the Theis (1935) equation by substitution. PMID- 22073981 TI - Effectiveness of classroom based crew resource management training in the intensive care unit: study design of a controlled trial. AB - BACKGROUND: Crew resource management (CRM) has the potential to enhance patient safety in intensive care units (ICU) by improving the use of non-technical skills. However, CRM evaluation studies in health care are inconclusive with regard to the effect of this training on behaviour and organizational outcomes, due to weak study designs and the scarce use of direct observations. Therefore, the aim of this study is to determine the effectiveness and cost-effectiveness of CRM training on attitude, behaviour and organization after one year, using a multi-method approach and matched control units. The purpose of the present article is to describe the study protocol and the underlying choices of this evaluation study of CRM in the ICU in detail. METHODS/DESIGN: Six ICUs participated in a paired controlled trial, with one pre-test and two post test measurements (respectively three months and one year after the training). Three ICUs were trained and compared to matched control ICUs. The 2-day classroom-based training was delivered to multidisciplinary groups. Typical CRM topics on the individual, team and organizational level were discussed, such as situational awareness, leadership and communication. All levels of Kirkpatrick's evaluation framework (reaction, learning, behaviour and organisation) were assessed using questionnaires, direct observations, interviews and routine ICU administration data. DISCUSSION: It is expected that the CRM training acts as a generic intervention that stimulates specific interventions. Besides effectiveness and cost-effectiveness, the assessment of the barriers and facilitators will provide insight in the implementation process of CRM. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1976. PMID- 22073982 TI - Molecular basis of early epithelial response to streptococcal exotoxin: role of STIM1 and Orai1 proteins. AB - Streptolysin O (SLO) is a cholesterol-dependent cytolysin (CDC) from Streptococcus pyogenes. SLO induces diverse types of Ca(2+) signalling in host cells which play a key role in membrane repair and cell fate determination. The mechanisms behind SLO-induced Ca(2+) signalling remain poorly understood. Here, we show that in NCI-H441 cells, wild-type SLO as well as non-pore-forming mutant induces long-lasting intracellular Ca(2+) oscillations via IP(3) -mediated depletion of intracellular stores and activation of store-operated Ca(2+) (SOC) entry. SLO-induced activation of SOC entry was confirmed by Ca(2+) add-back experiments, pharmacologically and by overexpression as well as silencing of STIM1 and Orai1 expression. SLO also activated SOC entry in primary cultivated alveolar type II (ATII) cells but Ca(2+) oscillations were comparatively short lived in nature. Comparison of STIM1 and Orai1 revealed a differential expression pattern in H441 and ATII cells. Overexpression of STIM1 and Orai1 proteins in ATII cells changed the short-lived oscillatory response into a long-lived one. Thus, we conclude that SLO-mediated Ca(2+) signalling involves Ca(2+) release from intracellular stores and STIM1/Orai1-dependent SOC entry. The phenotype of Ca(2+) signalling depends on STIM1 and Orai1 expression levels. Our findings suggest a new role for SOC entry-associated proteins in S. pyogenes-induced lung infection and pneumonia. PMID- 22073983 TI - Evaluation of gastrointestinal symptoms in different patient groups using the visual analogue scale for irritable bowel syndrome (VAS-IBS). AB - BACKGROUND: Irritable bowel syndrome (IBS) and gastrointestinal (GI) dysmotility disorders have a similar clinical picture, although dysmotility disorders require the attention of a specialist. Patients with primary Sjogren's syndrome (pSS) have also been described to suffer from IBS-like symptoms. No objective marker is available to distinguish between the patients. A visual analogue scale has been developed for IBS patients (VAS-IBS) to measure treatment response of GI symptoms and well-being in patients with IBS. The aim of the present study was to examine if VAS-IBS could be used to compare the degree of GI complaints in different patient populations, to get an objective marker to differentiate between the patients. METHODS: The VAS-IBS consists of 7 VAS scales, namely, abdominal pain, diarrhoea, constipation, bloating and flatulence, vomiting and nausea, psychological well-being and the intestinal symptoms' influence on daily life. Consecutive female patients suffering from IBS, dysmotility disorders and pSS were asked to complete the VAS-IBS questionnaire when visiting the out-patient clinics. In addition, a control population consisting of healthy female volunteers was included. RESULTS: Healthy volunteers had almost no GI symptoms, whereas all 3 patient groups expressed symptoms. There was no statistical significant difference between IBS and dysmotility in any of the scales besides vomiting and nausea (p = 0.044). Except for constipation, patients with pSS had less severe symptoms than the others. CONCLUSION: The VAS-IBS questionnaire could be used to assess the level of GI symptoms. However, VAS scores do not help the clinicians to differentiate between IBS and other dysmotility disturbances. PMID- 22073984 TI - A hermeneutic approach to the characteristics of mental health nursing practice. AB - Mental health nursing (MHN) takes a non-reductionist view of the human being, based on a hermeneutic and interdisciplinary perspective. MHN is dependent on the development of hermeneutic knowledge for understanding the deeper meaning of, for example, encountering a patient with emotional pain. The aim of this study was to provide a philosophical discussion about the characteristics of MHN practice. The hermeneutic approach was used to expand the philosophical discussion of MHN. In order to explore the consequences for MHN practice, previous relevant research within the discipline of MHN was used, exemplified by patients suffering from emotional pain. Two themes emerged: A reflective way of being and working and Relationships as a foundation for change and improvements. Four themes emerged related to the practice of the nurse: Desire for confirmation and trust, The vulnerable human being, The difficulties involved in responsibility and The power of self-development, authenticity and freedom. MHN must be open to changing some of the negative images of past interdisciplinary discussions in order to provide high quality care and support to the suffering patient. The hermeneutic approach is one way to help nurses who work in the context of mental health to understand and use their intuition and empathy to empower patients, thus providing hope and future possibilities. PMID- 22073985 TI - Analysis of chicken anemia virus genome: evidence of intersubtype recombination. AB - BACKGROUND: Chicken anemia virus (CAV) is the causative agent of chicken infectious anemia. CAV putative intergenotypic recombinants have been reported previously. This fact is based on the previous classification of CAV sequences into three genotypes. However, it is unknown whether intersubtype recombination occurs between the recently reported four CAV genotypes and five subtypes of genome sequences. RESULTS: Phylogenetic analysis, together with a variety of computational recombination detection algorithms, was used to investigate CAV approximately full genomes. Statistically significant evidence of intersubtype recombination was detected in the parent-like and two putative CAV recombinant sequences. This event was shown to occur between CAV subgroup A1 and A2 sequences in the phylogenetic trees. CONCLUSIONS: We revealed that intersubtype recombination in CAV genome sequences played a role in generating genetic diversity within the natural population of CAV. PMID- 22073986 TI - Luteolin induces apoptotic cell death through AIF nuclear translocation mediated by activation of ERK and p38 in human breast cancer cell lines. AB - The flavonoid, luteolin, has been shown to have anticancer activity in various cancer cells; however, the precise molecular mechanism of its action is not completely understood, and studies were conducted to find out how it induces apoptosis in breast cancer cells. Luteolin induced a reduction of viability in a dose- and time-dependent manner. The pro-apoptotic effect of luteolin was demonstrated by cell cycle measurement and Hoechst 3325 staining. Western blot analysis showed that luteolin activates ERK (extracellular-signal-regulated kinase) and p38. Pharmacological inhibition or knockdown of ERK and p38 protected against luteolin-induced cell death; however, the caspase-3-specific inhibitor had no effect. Immunocytochemical examination indicated that luteolin induced nuclear translocation of AIF (apoptosis-inducing factor), which was mediated by activation of ERK and p38. Transfection of a vector expressing the miRNA (microRNA) of AIF prevented luteolin-induced apoptosis. The data suggest that luteolin induces a caspase-dependent and -independent apoptosis involving AIF nuclear translocation mediated by activation of ERK and p38 in breast cancer cells. PMID- 22073988 TI - Knowledge and attitude of elderly persons towards dental implants. AB - BACKGROUND: Despite their unrivalled place in restorative treatment, dental implants are still scarcely used in elderly patients. INTRODUCTION: The aim of this survey was therefore to identify potential barriers for accepting an implant treatment. MATERIALS AND METHODS: Participants were recruited from a geriatric hospital, two long-term-care facilities and a private clinic. The final study sample comprised 92 persons, 61 women and 31 men with an average age of 81.2 +/- 8.0 years. In a semi-structured interview, the participants' knowledge of implants and attitude towards a hypothetical treatment with dental implants were evaluated. RESULTS: Twenty-seven participants had never heard of dental implants, and another 13 participants could not describe them. The strongest apprehensions against implants were cost, lack of perceived necessity and old age. Univariate and multiple linear regression analysis identified being women, type and quality of denture, having little knowledge on implants and being hospitalised as the risk factors for refusing implants. However, old age as such was not associated with a negative attitude. CONCLUSION: The acceptance of dental implants in the elderly population might be increased by providing further information and promoting oral health in general. Regardless of the age, dental implants should be placed when patients are still in good health and live independently. PMID- 22073987 TI - Exposure to gold nanoparticles produces cardiac tissue damage that depends on the size and duration of exposure. AB - BACKGROUND: Current research focuses on cancer therapy, diagnostics and imaging, although many challenges still need to be solved. However, for the application of gold nanoparticles (GNPs) in therapy and diagnostics it is necessary to know the bioaccumulation and local or systemic toxicity associated to them. The aim of the present study was to investigate the effects of intraperitoneal administration of GNPs on the histological alterations of the heart tissue of rats in an attempt to cover and understand the toxicity and the potential role of GNPs in the therapeutic and diagnostic applications. METHODS: Animals were randomly divided into 3 GNPs-treated rats groups and one control group (CG). The 10, 20 and 50 nm GNPs were administered intraperitonealy at the rate of 3 or 7 days as follows: Group 1: received infusion of 100 MUl GNPs of size 10 nm for 3 or 7 days; Group 2: received infusion of 100 MUl GNPs of size 20 nm for 3 or 7 days; Group 3: received infusion of 100 MUl GNPs of size 50 nm for 3 or 7 days. CONTROL GROUP: received no GNPs. RESULTS: In comparison with the respective control rats, GNPs treated rat received 100 MUl of 10 and 20 nm particles for 3 days or 7 days demonstrating congested heart muscle with prominent dilated blood vessels, scattered and extravasations of red blood cells, focus of muscle hyalinosis, disturbed muscle fascicles, dense prominent focus of inflammatory cells infiltrate by small lymphocytes and few plasma cells while GNPs-treated rat received 100 MUl of 50 nm particles for 3 or 7 days demonstrating benign normal looking heart muscle with normal muscle direction and fascicles, and very few scattered small lymphocytes. CONCLUSIONS: The histological alterations induced by intraperitoneal administration of GNPs were size-dependent with smaller ones induced more affects and related with time exposure of GNPs. This study suggests that interaction of GNPs with proteins and various cell types might be evaluated as part of the toxicological assessment in addition to further experiments related to tissues antioxidant enzymes, oxidative parameters, lipid peroxidation, production of free radicals and/or ROS and cytokine, histomorphologcal and ultrastrucural will be performed to cover and understand the toxicity and the potential use of GNPs as therapeutic and diagnostic tool. PMID- 22073989 TI - Fox gene loci in Takifugu rubripes and Tetraodon nigroviridis genomes and comparison with those of medaka and zebrafish genomes. AB - Members of the Fox gene family of transcriptional regulators are essential for animal development and have been extensively studied in vertebrates. The mouse and human genomes contain at least 40 FOX genes which are divided into 19 subclasses based on the sequence similarity of the highly conserved forkhead domain. Using the genome sequence of the Takifugu rubripes and Tetraodon nigroviridis , we examined the genomic complement of fox genes in these organisms to gain insight into the evolutionary relationship of this gene family. We identified 53 fox genes in Tetraodon nigroviridis and Takifugu rubripes genome by searching the forkhead domain. These genes are divided into 18 subclasses as follows: 8 fox genes in subclass O; 6 in subclass P ; 4 in subclasses D, J, and N; 3 in subclasses A, B, C, E, F, and I; 2 in subclasses K, L, and Q; and 1 in subclasses G, H, M, and R. Together with the forkhead domain sequences of human, chicken, frog, zebrafish, medaka, and Caenorhabditis elegans, the phylogenetic relationship of the fox genes in Takifugu rubripes and Tetraodon nigroviridis were analyzed and compared. The genes structure, general features, and the three dimensional model of these genes were also discussed. PMID- 22073990 TI - An international comparison of excessive adult mortality. AB - Abstract Empirical expressions derived by Coale and Demeny accurately characterized the relationships among death rates of different age groups for each sex during an extended period of time in Western nations. However, the relationships have changed in recent years, as the mortality of older persons has increasingly exceeded the level expected on the basis of these expressions. The recent disruption is relatively small for females and may be due to very rapid declines in maternal mortality. Among males, the change has been quite pronounced, and it is suggested that increases in cigarette consumption are largely responsible. PMID- 22073991 TI - The spread of anti-natal knowledge and practice in Nigeria. AB - Abstract In March/April 1969 the Demographic Training and Research Unit, University of Ife, surveyed 8,400 respondents of both sexes to investigate their knowledge and use of anti-natal practices and the sources of that knowledge. The area sampled was a stratified cross-section of Nigeria extending inland 500 miles from Lagos. Data are analysed by age cohorts of respondents and by the date of change in knowledge or practice. It is shown that anti-natal knowledge and practice decline with distance from Lagos, that contraception is widely practised amongst the richer towns and those with a higher proportion of educated people, and to a smaller extent among farmers than restricted knowledge or means would alone indicate. Recently the spread of both knowledge and practice has been faster than could be explained by socio-economic change and has largely resulted from changing attitudes to anti-natal practice and increased discussion of the subject in the world as a whole. Within Nigeria this has been helped by rising levels of urbanization and education, which are the two major determinants of anti-natal knowledge and practice in the country. The spread of such practice has led to an increased employment of traditional anti-natal methods, but this increase is small compared with the much greater resort now being made to modern contraception and induced abortion. The mass media have been of particular importance in introducing new knowledge, while the spread of such knowledge has owed most to discussions between friends of the same sex. PMID- 22073992 TI - Causes of fertility decline in Eastern Europe and the Soviet Union. AB - Abstract This is the first part of a wider study which attempts to throw iight on the demographic, economic and social factors that have led to dramatic declines in fertility levels in most socialist countries of Eastern Europe during the last fifteen years or so. The present part is concerned with the purely demographic influences, that is mainly with the impact of changes in the age and sex structure of the populations under study, and in nuptiality. The statistical evidence adduced indicates that the observed downward trends in the annual number of births and in crude birth rates are a reflection of genuine changes in attitudes towards family size. PMID- 22073993 TI - Bridal pregnancy in earlier rural England further examined. AB - Abstract This paper elaborates the argument of a previous paper (Population Studies, 20, 1966, pp. 233-43). The results of an investigation of the experience of 2,340 brides are broadly similar to those reported earlier: in particular, they confirm that bridal pregnancy was more common in the eighteenth than in the seventeenth century. Evidence is presented to suggest that the sixteenth-century experience was similar to that of the seventeenth, while the nineteenth-century experience was similar to that of the eighteenth. It is argued that bridal pregnancy was the product of a courting convention, rather than of 'betrothal licence', and that it was not especially common among widows or teenagers. It is incidentally shown that the interval between birth and baptism was very brief in the sixteenth century, but lengthened in later centuries; and that the forbidden seasons for marriage were gradually eroded. Finally, it is suggested that the application of Church discipline in relation to bridal pregnancy could be assessed in the Church Court records. PMID- 22073994 TI - Population growth in Java in the 19th century. AB - Abstract In demographic literature Java occupies a special position. It is the island where in the nineteenth century a 'population explosion' occurred. In other developing countries this took place in the twentieth century. Following the official figures Java had a population size of about 4.5 million in 1815 (Raffles's Census) and 28.5 million in 1900. The result is an extraordinary rate of growth of 2.2% per year. In this paper it is argued that it is impossible to correct the data by adjusting them. A more promising method is to study the factors which are responsible for the demographic situation, i.e. economic conditions, the so-called pax neerlandica and the health situation in the period 1800-1850. This period has been specially studied, because it is crucial for the calculation of population size which is normally based on the 1815 period. It is suggested that Java cannot really claim to be an exceptional case in the period 1800-1850. This means that the growth rate - in line with the estimates of Carr Saunders and Sauvy -has to be estimated (greater accuracy is not possible) as between 0.5% and 1.0); per annum. On the basis of estimates and calculations, the population size of Java may have been somewhere between 8 and 10 millions around 1800, the latter estimate being the more realistic figure. The view that there was exceptionally rapid population growth in Java in the nineteenth century is to an important degree the product of a Europe-centred approach to the history of Java. PMID- 22073995 TI - Users and non-users of contraception: Tests of stationarity applied to members of a family planning programme. AB - Abstract Regression analysis is used in examining the cumulative nature of contraceptive use among clients of a family planning programme. Markov chain analyses are performed on the data. chi(2) tests are used to test the stationarity of the transition probabilities from the state of user to non-user as well as from non-user to user over the period of operation of the programme. A good predictive equation is developed relating the cumulated number of users and the years of operation of the programme. The transition probabilities are not constant over the entire period of twelve years. The data are not homogeneous. When the twelve year-period is divided into three four-year periods, the transition probabilities are constant within each period. Each of these three periods coincides with a distinctive period in the development of the programme. PMID- 22073996 TI - The historical calendar as a method of estimating age: The experience of the Moroccan multi-purpose sample survey of 1961-63. AB - Abstract In censuses and surveys in most African countries it has become the practice to estimate informants' age by the method of the historical calendar. This involves an attempt to relate a remembered historical event, occurring during the subject's childhood, with his age at the time. This paper attempts a first evaluation of the method with particular reference to the 1961-63 multi round survey in rural Morocco. It is shown that in practice the method is highly complex and easily misunderstood by interviewers and respondents. An attempt to lay down a precise procedure by means of a very detailed questionnaire appeared to yield at best only marginally more accurate results than the simpler procedure used in an earlier round. The more complex questionnaire did, however, introduce new patterns of misuse by the interviewer. There was evidence that the historical calendar gave somewhat better data than eye estimates, but results were highly defective for both methods. It is clear that the method is far from perfect. Interviewer training and supervision remain the key to accurate age determination. If the potential benefits of the complex historical calendar method are to be realized, training and supervision need to be even more thorough than where simpler methods are used. PMID- 22073997 TI - Malaria eradication and the fall of mortality. AB - Abstract To evaluate the contradictory findings on the role of malaria eradication in the post-war reduction in mortality in Ceylon, the methods of analysis of Newman and Meegama are compared with one constructed by the present author. PMID- 22073998 TI - Leibenstein on the benefits and costs of birth control programmes. AB - Abstract Enke draws attention particularly to his recent dynamic models of the effects of birth prevention. He argues that the result of birth prevention is, typically, to leave future G.N.P. almost unaffected, with a smaller population and a reduction in the ratio of dependent children to the active age groups. G.N.P. per head is thus raised. Leibenstein accepts the relevance of population control and family planning programmes. He argues, however, that in its present form benefit-cost analysis does not provide a sound basis for estimating the value of such programmes. PMID- 22074001 TI - Healthcare costs in patients with metastatic lung cancer receiving chemotherapy. AB - BACKGROUND: To characterize healthcare resource utilization and costs in patients with metastatic lung cancer receiving chemotherapy in the US. METHODS: Using data from a large private multi-payer health insurance claims database (2000-2006), we identified all patients beginning chemotherapy for metastatic lung cancer. Healthcare resource use (inpatient, outpatient, medications) and costs were tallied over time from date of therapy initiation ("index date") to date of disenrollment from the health plan (in most instances, presumably due to death) or the end of the study period, whichever occurred first. Healthcare utilization and costs were characterized using Kaplan-Meier sample average methods. RESULTS: The study population consisted of 4068 patients; mean (SD) age was 65 (11) years. Over a median follow-up of 334 days, study subjects averaged 1.5 hospital admissions, 8.9 total inpatient days, and 69 physician office and hospital outpatient visits. Mean (95% CI) cumulative total healthcare costs were $125,849 ($120,228, $131,231). Costs of outpatient medical services and inpatient care constituted 34% and 20% of total healthcare costs, respectively; corresponding estimates for outpatient chemotherapy and other medication were 22% and 24%. CONCLUSION: Our study sheds additional light on the burden of metastatic lung cancer among patients receiving chemotherapy, in terms of total cost thru end of life as well as component costs by setting and type of service, and may be useful in informing medical resource allocation in this patient population. PMID- 22074003 TI - Total syntheses of ent-heliespirones A and C. AB - Stereodivergent total syntheses of ent-heliespirone A and C were both completed in 11 vessels and ~24% combined overall yield (A + C). These syntheses employed an identical inverse demand Diels-Alder reaction between a surrogate for an extendedly conjugated gamma-delta unsaturated ortho-quinone methide and L-lactic acid-derived exocyclic enol ether. Novel reactions of special note include a diastereoselective reduction of a chroman spiroketal by combination of borontrifluoride etherate and triethyl silane, along with oxidative rupture of a chroman etherial ring into the corresponding p-quinone by argentic oxide (AgO). In addition, an unusual intramolecular etherification of a 3 degrees alcohol caused by cerium ammonium nitrate was observed. PMID- 22074004 TI - Novel method for grafting alkyl chains onto glassy carbon. Application to the easy immobilization of ferrocene used as redox probe. AB - Primary alkyl iodides (RI) have been found to react with a cathodically charged glassy carbon surface at potentials more negative than -1.7 V vs Ag/AgCl. In aprotic solvents, this reaction results in grafting of the alkyl chains onto carbon. It is proposed that the process corresponds to the cathodic charge of graphitized and fullerenized zones present in carbon followed by a displacement reaction (analogous to a nucleophilic attack) toward alkyl iodides. This new mode of grafting is applied to the immobilization of ferrocene used as an electrochemical probe. The present work points out the reaction of omega iodoalkylferrocenes and quantifies the level of grafting of alkyl chains via this promising method for modification of carbon surfaces. Coverage levels were found to be high, reaching the apparent surface concentrations of 8 * 10(-9) mol cm( 2). These large values are explained on the basis of swelling of the interface provoked by progressive charging of the carbon surface via insertion of tetraalkylammonium cations concomitantly with the substitution process. Alkylferrocene layers deposited onto carbon were found to be chemically and electrochemically stable. PMID- 22074002 TI - Predictive value of metabolic 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy. AB - BACKGROUND: We aimed to study the predictive value of combined 18F-fluoro-deoxy-D glucose positron emission tomography and computerized tomography (FDG-PET-CT), on outcomes in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (C-CRT). METHODS: Thirty-two unresectable LAPC patients received 50.4 Gy (1.8 Gy/fr) of RT and concurrent 5-FU followed by 4 to 6 cycles of gemcitabine consolidation. Response was evaluated by FDG-PET-CT at post-C-CRT 12-week. Patients were stratified into two groups according to the median difference between pre- and post-treatment maximum standard uptake values (SUVmax) as an indicator of response for comparative analysis. RESULTS: At a median follow-up of 16.1 months, 16 (50.0%) patients experienced local/regional failures, 6 of which were detected on the first follow-up FDG-PET-CT. There were no marginal or isolated regional failures. Median pre- and post-treatment SUVmax and median difference were 14.5, 3.9, and -63.7%, respectively. Median overall survival (OS), progression-free survival (PFS), and local-regional progression free survival (LRPFS) were 14.5, 7.3, and 10.3 months, respectively. Median OS, PFS, and LRPFS for those with greater (N = 16) versus lesser (N = 16) SUVmax change were 17.0 versus 9.8 (p = 0.001), 8.4 versus 3.8 (p = 0.005), and 12.3 versus 6.9 months (p = 0.02), respectively. On multivariate analysis, SUVmax difference was predictive of OS, PFS, and LRPFS, independent of existing covariates. CONCLUSIONS: Significantly higher OS, PFS, and LRPFS in patients with greater SUVmax difference suggest that FDG-PET-CT-based metabolic response assessment is an independent predictor of clinical outcomes in LAPC patients treated with definitive C-CRT. PMID- 22074005 TI - Proteomic approach reveals FKBP4 and S100A9 as potential prediction markers of therapeutic response to neoadjuvant chemotherapy in patients with breast cancer. AB - Although doxorubicin (Doxo) and docetaxel (Docet) in combination are widely used in treatment regimens for a broad spectrum of breast cancer patients, a major obstacle has emerged in that some patients are intrinsically resistant to these chemotherapeutics. Our study aimed to discover potential prediction markers of drug resistance in needle-biopsied tissues of breast cancer patients prior to neoadjuvant chemotherapy. Tissues collected before chemotherapy were analyzed by mass spectrometry. A total of 2,331 proteins were identified and comparatively quantified between drug sensitive (DS) and drug resistant (DR) patient groups by spectral count. Of them, 298 proteins were differentially expressed by more than 1.5-fold. Some of the differentially expressed proteins (DEPs) were further confirmed by Western blotting. Bioinformatic analysis revealed that the DEPs were largely associated with drug metabolism, acute phase response signaling, and fatty acid elongation in mitochondria. Clinical validation of two selected proteins by immunohistochemistry found that FKBP4 and S100A9 might be putative prediction markers in discriminating the DR group from the DS group of breast cancer patients. The results demonstrate that a quantitative proteomics/bioinformatics approach is useful for discovering prediction markers of drug resistance, and possibly for the development of a new therapeutic strategy. PMID- 22074006 TI - Breakaways in specialist secure psychiatry. PMID- 22074007 TI - The reality is that the number of women with menopausal symptoms wanting to consider alternative therapies rather than hormone replacement therapy (HRT) has increased over the last decade. Introduction. PMID- 22074008 TI - Taking an integrated approach: managing women with phytoestrogens. AB - An integrated approach can be employed when counselling women about menopausal management options, where lifestyle, complementary therapies and hormone replacement therapy (HRT) are discussed. Women might opt to use an alternative approach to HRT for a variety of reasons, e.g. fear of side-effects and risks or contraindications to HRT. There are many choices of dietary and herbal approaches for menopausal symptoms, which essentially divide into food supplements and herbal medicines. The choice can often be overwhelming and confusing for the woman. Of concern, the evidence for efficacy and safety of some of these complementary therapies can be extremely limited or non-existent. In order to enable women to make a fully informed choice, it is important that, when a recommendation is made regarding a specific complementary therapy, it should focus on preparations for which a significant dataset exists for efficacy and safety and in which there is ongoing research and development. One of the most extensively studied food supplements has been the phytoestrogenic preparation containing red clover isoflavones. There have been six randomized trials thus far studying the impact on vasomotor symptoms, three of which have shown a significant benefit compared to placebo. There are also data from small randomized and observational trials showing positive outcomes for surrogate markers of osteoporosis and cardiovascular disease. A recent study using validated depression scales has shown that women using red clover isoflavones may also derive psychological benefits. Safety data are reassuring for the endometrium and breast, although further studies would be welcome, particularly in women with significant medical risks. PMID- 22074009 TI - Managing the menopause: practical choices faced in primary care. AB - Over the last 10 years, the management of the menopause has changed dramatically following the controversy surrounding hormone replacement therapy (HRT). Non-drug options have become increasingly popular with women and this has presented new challenges to us as their physicians. This report includes insights into how women feel about their menopause management, in particular their need to make an informed decision about their menopause management. This will ensure that they are committed to the option selected. Non-drug options should be viewed as a different approach to HRT, not as a substitute, and they should be recommended specifically to ensure that quality is assured. A guide is included as to how to select non-drug options, in particular for the phytoestrogen supplement products. Our role as physicians is to offer our patients the best possible choices to manage their health, and this should now include non-drug options that have been well-researched in terms of efficacy and safety. PMID- 22074010 TI - Self-assembly of dinitrosyl iron units into imidazolate-edge-bridged molecular squares: characterization including Mossbauer spectroscopy. AB - Imidazolate-containing {Fe(NO)(2)}(9) molecular squares have been synthesized by oxidative CO displacement from the reduced Fe(CO)(2)(NO)(2) precursor. The structures of complex 1 [(imidazole)Fe(NO)(2)](4), (Ford, Li, et al.; Chem. Commun.2005, 477-479), 2 [(2-isopropylimidazole)Fe(NO)(2)](4), and 3 [(benzimidazole)Fe(NO)(2)](4), as determined by X-ray diffraction analysis, find precise square planes of irons with imidazolates bridging the edges and nitrosyl ligands capping the irons at the corners. The orientation of the imidazolate ligands in each of the complexes results in variations of the overall structures, and molecular recognition features in the available cavities of 1 and 3. Computational studies show multiple low energy structural isomers and confirm that the isomers found in the crystallographic structures arise from intermolecular interactions. EPR and IR spectroscopic studies and electrochemical results suggest that the tetramers remain intact in solution in the presence of weakly coordinating (THF) and noncoordinating (CH(2)Cl(2)) solvents. Mossbauer spectroscopic data for a set of reference dinitrosyl iron complexes, reduced {Fe(NO)(2)}(10) compounds A ((NHC-iPr)(2)Fe(NO)(2)), and C ((NHC iPr)(CO)Fe(NO)(2)), and oxidized {Fe(NO)(2)}(9) compounds B ([(NHC iPr)(2)Fe(NO)(2)][BF(4)]), and D ((NHC-iPr)(SPh)Fe(NO)(2)) (NHC-iPr = 1,3 diisopropylimidazol-2-ylidene) demonstrate distinct differences of the isomer shifts and quadrupole splittings between the oxidized and reduced forms. The reduced compounds have smaller positive isomer shifts as compared to the oxidized compounds ascribed to the greater pi-backbonding to the NO ligands. Mossbauer data for the tetrameric complexes 1-3 demonstrate larger isomer shifts, most comparable to compound D; all four complexes contain cationic {Fe(NO)(2)}(9) units bound to one anionic ligand and one neutral ligand. At room temperature, the paramagnetic, S = (1)/(2) per iron, centers are not coupled. PMID- 22074012 TI - Reviews on animal diseases recently published in other journals. PMID- 22074011 TI - NKG2C deletion is a risk factor of HIV infection. AB - NK cell function is important in the immune response to HIV infection. NKG2C and NKG2A are activating and inhibitory NK cell receptors, respectively, and their only known ligand, HLA-E, demonstrates increased expression in HIV infection and presents at least one HIV-derived peptide. A variation in chromosome 12 exists in which the 16-kb section of DNA encompassing the nkg2c gene is completely absent. DNA samples of 433 HIV-1-infected patients and 280 controls were genotyped by PCR, and revealed an association of the absence variation with a higher risk of HIV infection, as well as faster progression and higher pretreatment viral loads (p<0.05, respectively). Surface NKG2C expression, analyzed by FACS, on the freshly isolated lymphocytes of 20 control and 19 HIV-infected donors revealed that NKG2C expression is genotype dependent in both populations: no NKG2C expression in the -/- groups, intermediate expression in the +/- groups, and highest expression in the +/+ groups. The comparison of NKG2C and NKG2A expression in HIV and control groups (+/- and +/+ included) indicates an increased NKG2C expression on HIV patient NK cells (p<0.05) and decreased inhibitory NKG2A expression on CD8 T cells (p<0.001), and both these effects are more striking in the +/+ genotype (p<0.005). Furthermore, a positive correlation was found between HIV viral load and the proportion of NKG2C(+) NK cells. The increased expression of NKG2C in HIV patients, in combination with the genetic association of the absence variation with an increased susceptibility to HIV infection, higher HIV viral set point, and a faster progression, indicate that NKG2C is important in the defense against HIV infection and progression. PMID- 22074016 TI - Severity of pandemic H1N1 2009 influenza virus infection may not be directly correlated with initial viral load in upper respiratory tract. AB - BACKGROUND: Recent studies have demonstrated that rapid influenza diagnostic tests (RIDTs) have a relatively low sensitivity in detecting severe cases of pandemic H1N1 2009 influenza virus (pH1N1) infection. We hypothesized that viral load in upper respiratory specimens obtained on presentation may not be correlated with disease severity. METHODS: We conducted a prospective study to compare patterns of viral shedding using nasopharyngeal swab specimens, according to the number of days of post-symptom onset and post-antiviral therapy, between patients with and without complications. RESULTS: From July 15, 2009 through July 23, 2010, we collected and processed a total of 141 nasopharyngeal swab specimens from 64 inpatients and outpatients with laboratory-confirmed pH1N1 infection. These included 46 patients without any complications (uncomplicated group) and 18 patients who required hospital admission (complicated group). The mean initial viral load was higher in the uncomplicated group than in the complicated group (3.4 +/- 1.6 log(10) copies/MUl versus 1.9 +/- 1.7, P = 0.02). However, prolonged viral shedding was only detected in the complicated group (44% by day 7 of antiviral therapy). By multivariate analysis, we found that age (OR, 1.1; 95% CI, 1.0-1.1) and initial nasopharyngeal viral load (OR, 0.5; 95% CI, 0.3-0.8) were significant factors associated with complications. CONCLUSION: Given that patients with severe pH1N1 infection may have relatively lower initial viral load in the upper respiratory tract, cautious interpretation of negative RIDT results is particularly warranted in this patient population. PMID- 22074015 TI - Benefits of the HiRes 120 coding strategy combined with the Harmony processor in an adult European multicentre study. AB - CONCLUSION: The Harmony processor was found to be reliable, comfortable and offered a substantially increased battery life compared with the previous generation processor. No significant improvement in speech understanding with HiRes was demonstrated from objective measures, but the majority of subjects showed a clear subjective preference for the combination HiRes 120/Harmony processor. OBJECTIVES: To evaluate experience with the HarmonyTM sound processor, together with the HiRes 120 strategy. METHODS: Postlingually deafened adults implanted with a CII or HiRes 90K were included and divided into three groups: (1) experienced users using the Platinum body-worn processor; (2) experienced users who had been using other processors; (3) new users with the Harmony processor from first fitting. The latter group entered a randomized crossover protocol where half were initially fitted with HiRes and half with HiRes 120. The initial strategy was used for 3 months and the alternative for a further 3 months. Speech perception tests and questionnaires were performed. RESULTS: The study included 65 subjects. Implementing HiRes 120 was straightforward. The speech test group results did not show significant differences between HiRes and HiRes 120. However, the questionnaires showed significantly higher ratings for HiRes 120 in some instances. Subjects were highly satisfied with the Harmony processor. PMID- 22074017 TI - The effects of exenatide bid on metabolic control, medication use and hospitalization in patients with type 2 diabetes mellitus in clinical practice: a systematic review. AB - The objective of this systematic review was to assess the published literature on the effectiveness of exenatide twice daily (exenatide) in clinical practice, specifically its effects on haemoglobin A1c (A1C), fasting glucose (FG), weight, systolic blood pressure (SBP), medication use, hospitalization and cardiovascular disease (CVD) outcomes. A systematic literature search using the MEDLINE database of English language literature published between January 2005 and May 2011 was performed. The review included retrospective or prospective observational studies that included 100 or more patients per treatment group. A total of 15 studies meeting the inclusion criteria were identified. The studies revealed significant reductions of -0.4 to -0.9% in A1C, -10 mg/dl in FG, -2 to -11 kg in body weight and -2 to -11 mmHg in SBP. Statistically significant reductions in the use or dosage of either oral glucose-lowering medications or insulin after initiating exenatide treatment were found in every observational study that assessed medication changes, including reductions in dosage of up to 75% in sulphonylureas dosages, 22% in metformin, 66% in thiazolidinediones (TZD) or TZD combination therapy and 75% in prandial insulin. Exenatide-treated patients experienced significantly lower rates of all-cause and CVD-related hospitalization and CVD events than patients treated with other therapies overall. In this review of observational studies, exenatide initiation was associated with significant reductions in clinically relevant outcomes. Improvements in A1C, FG, weight and SBP in the observational studies in this review were consistent with improvements observed in controlled clinical trials. PMID- 22074018 TI - Encephalomyelitis associated with microsporidian infection in farmed greater amberjack, Seriola dumerili (Risso). AB - An outbreak of a disease characterized by a peculiar spiral movement in farmed greater amberjack, Seriola dumerili (Risso), occurred in Kagoshima Prefecture, Japan, in May 2008, immediately after importing the fish from China. Although neither bacteria nor viruses were detected in routine diagnostic tests, histopathological observations of the affected fish revealed severe inflammation in the tegmentum of the brain including the medulla oblongata and the anterior part of the spinal cord. In addition, a microsporidian parasite was observed in the nerve cell bodies or axons in the inflamed tissues. We identified a microsporidian small subunit rRNA gene (SSU rDNA) from the lesion, and the sequence showed 96.1% identity with that of Spraguea lophii. Subsequent in situ hybridization using probes presumably specific to the SSU rRNA confirmed that the parasite observed in histopathology harboured the identified SSU rRNA. Apparently degenerated microsporidian cells or spores were also frequently observed in tissue sections. Thus, the disease was most probably caused by the infection of a hitherto unknown microsporidian parasite that has a genetic affinity to the genus Spraguea, in the central nervous system of the amberjack. PMID- 22074019 TI - Clinical observations of black disease in fairy shrimps, Streptocephalus sirindhornae and Branchinella thailandensis, from Thailand and pathogen verification. AB - In this study, black disease infecting fairy shrimps, Streptocephalus sirindhornae Sanoamuang, Murugan, Weekers & Dumont, and Branchinella thailandensis Sanoamuang, Saengphan & Murugan, in Thailand, was investigated. The typical signs of the disease are the appearance of black spots on the cuticle, located mainly on the dorsal side and thoracopods. A number of rod-shaped bacteria aggregated in the black spots and were visualized by scanning electron microscopy. The histopathological results showed that a haemocytic response to the infection resulted in a dense melanized core of bacteria. In addition, generalized septicaemia by rod-shaped bacteria was also observed in the infected tissue. Of the 31 isolates, Aeromonas spp. were predominantly isolated and six strains were selected for the experimental infections. The most pathogenic strain was identified molecularly as A. hydrophila. When fairy shrimp were infected at bacterial concentrations of 10(4) and 10(6) cfu mL(-1) , the overall infection levels were 73.33 +/- 6.67% and 93.33 +/- 6.67%, respectively. The experimentally infected fairy shrimp showed abnormal swimming and died within 24-48 h after the appearance of the dark pigment. PMID- 22074020 TI - Protection of grass carp, Ctenopharyngon idellus (Valenciennes), through oral administration of a subunit vaccine against reovirus. PMID- 22074021 TI - Khawia japonensis (Cestoda: Caryophyllidea): another invasive parasite of carp, Cyprinus carpio L., imported to Europe. PMID- 22074022 TI - Surgical removal of a gastric foreign body in a sand tiger shark, Carcharias taurus Rafinesque. PMID- 22074023 TI - Prevalence of piscine myocarditis virus (PMCV) in marine fish species. PMID- 22074024 TI - Psychometric properties of the Turkish version of the perception of aggression scale. AB - The aim of this study was to investigate the psychometric properties of the Turkish version of the Perception of Aggression Scale. Cross-sectional data were collected by the completion of questionnaires by 350 nursing students from two nursing schools in Istanbul, Turkey. The psychometric properties of the Turkish version of the scale were analysed by using factor analysis (principal component analysis), assessment of internal consistency and reliability, and Spearman's rank correlation coefficients. The two-factor structure was confirmed by principal component analysis: the first factor treated aggression as functional and the second as dysfunctional. The correlation between the means of the items and dimensions was moderate (r for factor 1: 0.47-0.73; r for factor 2: 0.29 0.70). The coefficient of internal consistency of the scale was 0.85 for factor 1 and 0.81 for factor 2. Thus, Turkish version of Perception of Aggression Scale is a valid and reliable tool. It is essential to understand perceptions of aggressive behaviour in order to establish effective management strategies to tackle untoward events in clinical settings. PMID- 22074025 TI - Evolution of the large genome in Capsicum annuum occurred through accumulation of single-type long terminal repeat retrotransposons and their derivatives. AB - Although plant genome sizes are extremely diverse, the mechanism underlying the expansion of huge genomes that did not experience whole-genome duplication has not been elucidated. The pepper, Capsicum annuum, is an excellent model for studies of genome expansion due to its large genome size (2700 Mb) and the absence of whole genome duplication. As most of the pepper genome structure has been identified as constitutive heterochromatin, we investigated the evolution of this region in detail. Our findings show that the constitutive heterochromatin in pepper was actively expanded 20.0-7.5 million years ago through a massive accumulation of single-type Ty3/Gypsy-like elements that belong to the Del subgroup. Interestingly, derivatives of the Del elements, such as non-autonomous long terminal repeat retrotransposons and long-unit tandem repeats, played important roles in the expansion of constitutive heterochromatic regions. This expansion occurred not only in the existing heterochromatic regions but also into the euchromatic regions. Furthermore, our results revealed a repeat of unit length 18-24 kb. This repeat was found not only in the pepper genome but also in the other solanaceous species, such as potato and tomato. These results represent a characteristic mechanism for large genome evolution in plants. PMID- 22074026 TI - Apolipoprotein E mRNA expression in mononuclear cells from normolipidemic and hypercholesterolemic individuals treated with atorvastatin. AB - BACKGROUND: Apolipoprotein E (apoE) is a key component of the lipid metabolism. Polymorphisms at the apoE gene (APOE) have been associated with cardiovascular disease, lipid levels and lipid-lowering response to statins. We evaluated the effects on APOE expression of hypercholesterolemia, APOE epsilon2/epsilon3/epsilon4 genotypes and atorvastatin treatment in Brazilian individuals. The relationship of APOE genotypes and plasma lipids and atorvastatin response was also tested in this population. METHODS: APOE epsilon2/epsilon3/epsilon4 and plasma lipids were evaluated in 181 normolipidemic (NL) and 181 hypercholesterolemic (HC) subjects. HC individuals with indication for lowering-cholesterol treatment (n = 141) were treated with atorvastatin (10 mg/day/4-weeks). APOE genotypes and APOE mRNA in peripheral blood mononuclear cells (PBMC) were analyzed by TaqMan real time PCR. RESULTS: HC had lower APOE expression than NL group (p < 0.05) and individuals with low APOE expression showed higher plasma total and LDL cholesterol and apoB, as well as higher apoAI (p < 0.05). Individuals carrying epsilon2 allele have reduced risk for hypercholesterolemia (OR: 0.27, 95% I.C.: 0.08-0.85, p < 0.05) and NL epsilon2 carriers had lower total and LDL cholesterol and apoB levels, and higher HDL cholesterol than non-carriers (p < 0.05). APOE genotypes did not affect APOE expression and atorvastatin response. Atorvastatin treatment do not modify APOE expression, however those individuals without LDL cholesterol goal achievement after atorvastatin treatment according to the IV Brazilian Guidelines for Dyslipidemia and Atherosclerosis Prevention had lower APOE expression than patients with desirable response after the treatment (p < 0.05). CONCLUSIONS: APOE expression in PBMC is modulated by hypercholesterolemia and the APOE mRNA level regulates the plasma lipid profile. Moreover the expression profile is not modulated neither by atorvastatin nor APOE genotypes. In our population, APOE epsilon2 allele confers protection against hypercholesterolemia and a less atherogenic lipid profile. Moreover, low APOE expression after treatment of patients with poor response suggests a possible role of APOE level in atorvastatin response. PMID- 22074028 TI - Effect of weight gain during pregnancy on heart rate variability and hypotension during caesarean section under spinal anaesthesia. AB - The purpose of this study was to assess the effect of antenatal weight gain on baseline heart rate variability and incidence of hypotension in singleton parturients with a normal pre-pregnancy body mass index, presenting at term for elective caesarean section under spinal anaesthesia. Sixty-six parturients, of ASA physical status 1-2, were allocated to one of three groups according to their weight gain during pregnancy: < 11 kg; 11-16 kg; and > 16 kg. Mean (SD) approximate entropy of baseline heart rate was significantly higher in the < 11 kg group (0.27 (0.11)) compared with the 11-16 kg group (0.14 (0.08)) and the > 16 kg group (0.14 (0.07)) (both p < 0.001). The incidence of hypotension in the < 11 kg group (17/22; 77%) was significantly higher than in the 11-16 kg group (7/22; 32%) (p = 0.006) and the > 16 kg group (8/22; 36%) (p = 0.01). We conclude that weight gain < 11 kg during pregnancy is associated with increased baseline heart rate variability and a higher incidence of hypotension at the time of elective caesarean section under spinal anaesthesia. PMID- 22074027 TI - The influence of double flask investing on tooth displacement in dentures processed by microwave irradiation. AB - OBJECTIVE: This study evaluated the influence of the bimaxillary flask (BMF) and two different investing materials on first molar inclination in dentures processed by microwave irradiation. BACKGROUND: The BMF may minimise tooth displacement, saving time and improving occlusion. METHODS AND MATERIALS: Forty pairs of dentures were randomised into four groups: stone wall in monomaxillary flask; silicone wall in BMF; stone wall in BMF; acrylic resin retentions and silicone in BMF. Dentures were processed by microwave irradiation. Two referential points were established on tooth surface. A microscope and a digital pachymeter were used to measure the distance between these points, and the angles alpha (right maxillary molar), beta (left maxillary molar), alpha' (right mandibular molar) and beta' (left mandibular molar) were calculated by the law of cosines. Data were submitted to Kruskal-Wallis (5% significance). RESULTS: No difference was observed among the groups (p > 0.05). In the intra-group analysis, alpha was significantly different for groups I, II and III; alpha', for groups II and IV; beta, for all groups; beta', for groups III and IV. CONCLUSION: First molar inclination was similar for monomaxillary and BMFs. The use of stone or silicone as investing materials presented the same effect on tooth inclination. PMID- 22074029 TI - The effect of sterilisation on the plasticity of multi-use Eschmann gum elastic bougies: a bench and manikin study. AB - We investigated the deterioration in plasticity of the multi-use Portex Tracheal Guide ('bougie') with repeated sterilisation. Six bougies were prepared by washing them between 0 and 100 times (in accordance with the manufacturer's guidelines). Two tests were employed: a bench test in which rapid serial photographs were taken of the bougies uncoiling from a preformed curve; and a manikin-based test in which the six bougies were used in a simulated difficult airway. The bench test demonstrated a progressive deterioration in plasticity with repeated washing. However, the manikin-based test showed no significant difference between bougies in the incidence of oesophageal placement (p = 0.74). Time to placement differed significantly only between the two most-washed bougies but was broadly similar. We suggest therefore that the manufacturer's limit of five washings may be unnecessarily cautious. PMID- 22074030 TI - Treatment of cocaine overdose with lipid emulsion. AB - We describe the management and recovery of a 28-year-old man following a history of overdose by nasal inhalation of cocaine. The patient was presented in a comatose state suffering from seizures and marked cardiovascularly instability. Intravenous lipid emulsion was administered following initial resuscitation and tracheal intubation, as a means of treating persistent cardiac arrhythmias and profound hypotension. Following lipid emulsion therapy, the patient's life threatening cardiovascular parameters rapidly improved and he recovered well without any side effects, thus being discharged within 2 days. PMID- 22074031 TI - In vitro transactivation potencies of black-footed albatross (Phoebastria nigripes) AHR1 and AHR2 by dioxins to predict CYP1A expression in the wild population. AB - Our previous studies have detected high levels of dioxins and related compounds (DRCs) including polychlorinated dibenzo-p-dioxins (PCDDs), furans (PCDFs), and coplanar PCBs (Co-PCBs) in the black-footed albatross (BFA), Phoebastria nigripes, from the North Pacific region. We have also cloned two aryl hydrocarbon receptors, AHR1 and AHR2, of the BFA. To evaluate the sensitivity to DRCs in the BFA and to assess the status of cytochrome P450 1A (CYP1A) induction in the wild population, this study investigated the mRNA expression levels of BFA AHR1 and AHR2 and also the transactivation potencies of each AHR by 15 selected DRC congeners. Quantitative real-time PCR of BFA AHR mRNAs showed that hepatic AHR1 is more highly expressed than AHR2. Transactivation by graded concentrations of individual DRCs was measured in COS-7 cells, where BFA AHR1 or AHR2 was transiently transfected. For congeners that exhibited AHR-mediated dose-dependent activities, 50% effective concentration (EC(50)) and 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) relative potencies (REPs) were estimated. Based on the estimates of the REPs, TCDD induction equivalency factors (IEFs) were determined. For BFA AHR1, PeCDF was equipotent to TCDD, but other congeners exhibited lower IEFs. For BFA AHR2, PCDD/F congeners except OCDD/F showed IEFs >= 1.0. Using BFA AHR1- or AHR2-IEFs and hepatic concentrations of DRCs in North Pacific BFAs, TCDD induction equivalents (IEQs) were calculated. We further constructed nonlinear regression models on the relationships between BFA AHR1- or AHR2-IEF derived total IEQ or WHO-TEF derived total TEQ and ethoxyresorufin-O-deethylase activity (EROD) in the liver of wild BFAs. The results indicated that the relationships of BFA AHR1- and AHR2-based IEQs and EROD were predictable from BFA AHR1- and AHR2 mediated transactivation by TCDD, respectively. Collectively, these results suggest that the in vitro assay incorporating the AHR of species of concern would be a useful tool to predict the sensitivity to DRCs in the species and CYP1A induction in the wild population. PMID- 22074032 TI - Formation of a "hard microemulsion" and its role in controllable synthesis of nanoparticles within a functional polymer matrix. AB - Microemulsions are often used in the synthesis of nanoparticles in solution. In this work, we put forward the concept of a "hard microemulsion", which is based on the differential partitioning of water and ethanol solvent molecules inside functional polymer matrices. When the mixture of water and organic solvent enters the functional polymer, the liquid molecules should partition to different regions. Water should concentrate in the microdomains rich in hydrophilic functional groups, forming water-enriched cores, whereas organic solvents should localize near the alkyl polymer skeleton, forming organic liquid enriched outer layers. From a macroscopic view, the swollen polymer matrix is divided into numerous "microdroplets", resembling frozen water-in-oil microemulsions. We define such a structure as a "hard microemulsion". The water-enriched microdroplets may act as templates for synthesizing inorganic nanoparticles. We demonstrate the utility of hard microemulsions for the controllable synthesis of silver and platinum nanoparticles inside different macroreticular functional polymers. PMID- 22074033 TI - Association of the T45G and G276T polymorphisms in the adiponectin gene with PCOS: A meta-analysis. AB - Adiponectin is the most abundant adipocytokine in human body and may play a role in the pathogenesis of polycystic ovary syndrome (PCOS). To clarify the conflicting data in the literature concerning the association between PCOS and two polymorphisms of the adiponectin gene, T45G and G276T, a meta-analysis was performed in this study. Literature search was conducted through PubMed, EMBASE and other relevant studies. Pooled odds ratios (OR) were estimated using fixed effects (FE) models in codominant, recessive and dominant models. Sensitive analysis was performed by excluding invalid studies. Eight articles investigated the T45G polymorphism in PCOS, and five publications are associated with the G276T polymorphism in PCOS. Significant associations of adiponectin T45G polymorphism with PCOS were found in codominant (FEM: OR = 1.36, 95% CI: 1.12 1.65), recessive (FEM: OR = 2.02, 95% CI: 1.17-3.47) or dominant models (FEM: OR = 1.33, 95% CI: 1.06-1.67). For adiponectin G276T polymorphism, the OR and 95% CI are 0.81(0.68, 0.98), 0.74(0.51, 1.09) and 0.78 (0.61, 0.99) in codominant, dominant and recessive models, respectively. This study provides positive evidence for a causal relationship between the adiponectin gene and PCOS which needs to be further confirmed by further studies. PMID- 22074034 TI - China's birth control action programme, 1956-1964. AB - Abstract Drawing upon available information this article throws light on China's birth control action programme, focusing on (1) its organizational set up, (2) the modes of communication, persuasion and pressure employed, (3) products and services provided, and (4) strategies resorted to. The Chinese approach to the birth control campaign has been characterized by two distinct and related strategies: (1) 'tien hsien mien hou' strategy, and (2) 'mass campaign' strategy. According to the first strategy - literally 'point first space later' - the organized efforts are to be concentrated initially on the upper socio economic strata and major urban areas, then gradually extended to cover lower strata and lesser cities, and eventually expanded to encompass the entire rural areas. This strategy also means that at the regional level a pilot project should be undertaken first, and the experience subsequently employed to tackle a larger area. The 'mass campaign' strategy means conducting crash, intensive, extensive and intermittent publicity campaigns, involving all means of communication at the regime's disposal. PMID- 22074035 TI - Family, fertility, and sex ratios in the British Caribbean. AB - Abstract This paper re-evaluates the currently held view that unstable forms of conjugal unions depress fertility in the British Caribbean. It is shown that previous investigators overlooked the important variable of persistent male shortages at the mating ages caused by heavy male emigration. Fertility trends are observed and the conclusion reached that male emigration (independent variable) has not adversely affected fertility because the 'informal' polygynous character of the mating system acts as an intermediate variable mitigating the effect of the independent variable on fertility. Given these male shortages it is argued that a trend toward greater stability in conjugal relations would not, as previously assumed, result in higher fertility because permanent female celibacy and the average age of first entry into sexual unions for females would rise. Finally, the paper concludes by commenting on a recent discussion concerning the causal relationship between male shortages and the persistence of marital instability in the British Caribbean. The position is taken that both of these conditions are caused by social and economic factors which are not likely to change in the near future. PMID- 22074036 TI - Net delay of next conception by contraception: A highly simplified case. AB - Abstract A probability model, building on the work of Perrin and Sheps, is presented and applied. The model makes it possible to follow a cohort of women from a pregnancy outcome to next conception. Principal simplifying assumptions are homogeneity among women and constant fecundity. Cases treated include no contraception; a single contraceptive method practised; and a second contraceptive method practised following a first one. Expected durations to next conception may be calculated in relation to the following factors: outcome of previous pregnancy, length of anovulation, natural fecundability, time first contraceptive method is initiated, characteristics of first contraceptive (effectiveness and continuation rate), characteristics of second contraceptive, and gap between termination of first and commencing second contraceptive. By suitably pairing runs of the model, one can construct experiments in which the only differentiating factor is use and non-use of a specified contraceptive, and, by differencing the corresponding mean durations to next conception, compute the net delay of next conception produced by that contraceptive. PMID- 22074037 TI - Changing patterns of family growth: The value of linked vital records as a source of data. AB - Abstract Marriage and birth registrations for the Canadian province of British Colombia have been 'linked' by computer into family groupings to provide reproductive histories of married couples. The usefulness of the approach is illustrated by a comparison of the early productivities of marriages contracted in 1961 and in 1951, taking into account the age of the bride, the duration of the marriage, and the religions of the groom, bride and officiating clergyman. Older Catholic brides are shown to run counter to the otherwise general trend towards increasing productivity in the early years of marriage. PMID- 22074038 TI - A study of Irish county marriage rates, 1961-1966. AB - Abstract This article considers a group of models of Irish county marriage rates. Some of these models account for the major part of the inter-county variation in male and female marriage rates in terms of the influence of a limited number of socio-economic variables. The sex ratio of the unmarried population in the counties plays a key role in all of the models: the female marriage rate tends to be raised, and the male rate lowered, by a high ratio of males to females in the unmarried population. Male rates appear to increase under more favourable economic conditions, as measured by county income per person, while female rates appear to be lowered by increased female participation in the labour force. In addition to these separate influences on male and female rates, a recursive model in which there is a one-way influence from male to female rates, and a simultaneous-equation model, in which male and female rates are fully interdependent, were tested. The performance of the tested recursive model was particularly satisfactory. PMID- 22074039 TI - International migration of professionals. AB - Abstract Using chiefly data published by the U.S. Immigration and Naturalization Service this paper presents a statistical summary of the trends in professional immigration into the United States. The proportion of immigrants who are professionals has been steadily increasing during recent decades, and change in immigration laws produced a sharper increase since 1965. The second trend of importance is the increasing proportion of professional immigrants who come from the less developed nations of the world. The effects of immigration on American science and medicine are discussed. Important benefits appear to have accrued to the U.S. The effects on the countries of origin are less beneficial. Finally, the reasons behind the migration of professionals are discussed. PMID- 22074040 TI - On the relation between economic status and family size preferences when status differentials in contraceptive instrumentalities are eliminated. AB - Abstract In this paper an attempt is made to formalize the essential elements of a theory of reproductive motivation outlined by Judith Blake in a recent article. On the basis of the results of that exercise, it is argued that the theory, as it stands now, is not specific enough to 'predict' whether the affluent would choose to have fewer children than the poor, if contraceptive instrumentalities were to be equalized among the economic strata. It is also argued that the negative (though weak) association between ideal family size and economic status and the non-negative association between desired number of children and economic status, observed in survey data, are both consistent with the basic premisses of the theory under reference. PMID- 22074041 TI - The incidence of spontaneous abortion. AB - Abstract Published data are reviewed and it is concluded that about one fertilized ovum in three perishes before pregnancy is recognised. Of those surviving until pregnancy is recognized, one in four or five perish before term. So spontaneous loss accounts for about one fertilized ovum in two in a medically advanced society. PMID- 22074042 TI - Causes of fertility decline in Eastern Europe and the Soviet Union II. AB - Abstract The first part of this study (which appeared in the preceding issue of Population Studies) assessed the extent of the decline in fertility in the countries of the area during the last 10-15 years, and analyzed the purely demographic aspects ofthis phenomenon. Part II examines the socio-economic differentials in fertility, with regard to such variables as urban-rural residence, socio-occupational and employment status of women, educational attainment, income and housing conditions, and the consequent impact of structural changes in these characteristics of the population on observed fertility trends. The broad conclusion is that the fertility differentials usually found in western societies are also relevant to the socialist countries of eastern Europe, and that the dramatic falls in fertility in the 1950's and the 1960's have largely been the outcome ofthe deep and rapid structural changes, particularly those associated with urbanization, educational attainment and the incidence of female employment. The last part of the study is concerned with the impact on post-war fertility trends of social legislation and of general economic policies, particularly in the fields of employment and income. An appraisal of the extent of family planning is followed by a discussion of the recent pro-natalist measures introduced in most countries of the area and of their effectiveness. PMID- 22074045 TI - The FGF and FGFR Gene Family and Risk of Cleft Lip With or Without Cleft Palate. AB - Background : Isolated, nonsyndromic cleft lip with or without cleft palate is a common human congenital malformation with a complex and heterogeneous etiology. Genes coding for fibroblast growth factors and their receptors (FGF/FGFR genes) are excellent candidate genes. Methods : We tested single-nucleotide polymorphic markers in 10 FGF/FGFR genes (including FGFBP1, FGF2, FGF10, FGF18, FGFR1, FGFR2, FGF19, FGF4, FGF3, and FGF9) for genotypic effects, interactions with one another, and with common maternal environmental exposures in 221 Asian and 76 Maryland case-parent trios ascertained through a child with isolated, nonsyndromic cleft lip with or without cleft palate. Results : Both FGFR1 and FGF19 yielded evidence of linkage and association in the transmission disequilibrium test, confirming previous evidence. Haplotypes of three single nucleotide polymorphisms in FGFR1 were nominally significant among Asian trios. Estimated odds ratios for individual single-nucleotide polymorphic markers and haplotypes of multiple markers in FGF19 ranged from 1.31 to 1.87. We also found suggestive evidence of maternal genotypic effects for markers in FGF2 and FGF10 among Asian trios. Tests for gene-environment (G * E) interaction between markers in FGFR2 and maternal smoking or multivitamin supplementation yielded significant evidence of G * E interaction separately. Tests of gene-gene (G * G) interaction using Cordell's method yielded significant evidence between single-nucleotide polymorphisms in FGF9 and FGF18, which was confirmed in an independent sample of trios from an international consortium. Conclusion : Our results suggest several genes in the FGF/FGFR family may influence risk for isolated, nonsyndromic cleft lip with or without cleft palate through distinct biological mechanisms. PMID- 22074046 TI - Perceptions and practices of pharmaceutical wholesalers surrounding counterfeit medicines in a developing country: a baseline survey. AB - BACKGROUND: Recent investigations by the Ministry of Health of Cambodia suggest that counterfeit medicines have been introduced into the pharmaceutical market in tampered packaging. To further explore this possibility, an interview survey was conducted at the wholesaler level to investigate the medicinal supply chain in Cambodia. METHODS: Managing executives of 62 (83.8%) registered wholesalers of modern medicines in Cambodia were interviewed in 2009 on their knowledge of, perception on, and practices related to counterfeiting issues through a semi structured questionnaire. RESULTS: According to our findings, 12.9% of the wholesalers had encountered counterfeit medicine. However, they demonstrated a variety of perceptions regarding this issue. A majority (59.7%) defined counterfeit medicines as medicines without registration, while other definitions included medicines that were fraudulently manufactured, medicines without a batch/lot number, those containing harmful ingredients or a reduced amount of active ingredients, and expired medicines. Additionally, 8.1% responded that they did not know what counterfeit medicines were.During procurement, 66.1% of the wholesalers consider whether the product is registered in Cambodia, while 64.5% consider the credibility and quality of the products and 61.3% consider the reputation of the manufacturers. When receiving a consignment, 80.6% of wholesalers check the intactness of medicines, 72.6% check the specification and amount of medicines, 71% check Cambodian registration, 56.5% check that the packaging is intact, 54.8% check batch and lot numbers, 48.4% check the dates of manufacture and expiration, and 9.7% check analytical certificates.Out of 62 wholesalers, 14.5% had received medicines that arrived without packages or were separated from their packaging and had to be repacked before distribution. Significant statistical association was found between wholesalers who received medicines separately from their packs/containers and who consider their belief on reliability of pharmaceutical products of certain manufacturing country during procurement (Chi-square: 12.951, P = 0.002). When wholesalers divide medicines from larger packs into smaller ones, 54.8% use packaging purchased from local markets. CONCLUSION: A number of wholesalers think counterfeit medicines are medicines without registration, and/or do not have any uniform ideas on the issue and what to do, when they find or suspect counterfeits. Furthermore, their strict adherence to anti-counterfeiting measures is urgently needed. PMID- 22074047 TI - Secretome of the free-living mycelium from the ectomycorrhizal basidiomycete Laccaria bicolor. AB - The ectomycorrhizal basidiomycete Laccaria bicolor has a dual lifestyle with a transitory soil saprotrophic phase and a longer mutualistic interaction with tree roots. Recent evidence suggests that secreted proteins play key roles in host plant colonisation and symbiosis development. However, a limited number of secreted proteins have been characterized, and the full spectrum of effectors involved in the mycobiont invasion and survival remains unknown. We analyzed the extracellular proteins secreted in growth medium by free-living mycelium of L. bicolor as a proxy for its saprotrophic phase. The proteomic analyses (two dimensional electrophoresis and shotgun proteomics) were substantiated by whole genome expression transcript profiling on ectomycorrhizal roots. Among the 224 proteins identified were carbohydrate-acting enzymes likely involved in the cell wall remodelling linked to hyphal growth as well as secreted proteases possibly digesting soil organic compounds and/or fending off competitors, pathogens, and predators. Evidence of gene expression was found in ectomycorrhizal roots for 210 of them. These findings provide the first global view of the secretome of a mutualistic symbiont and shed some light on the mechanisms controlling cell wall remodelling during the hyphal growth. They also revealed many novel putative secreted proteins of unknown function, including one mycorrhiza-induced small secreted protein. PMID- 22074048 TI - Hepatitis B core IgM antibody (anti-HBcIgM) among hepatitis B surface antigen (HBsAg) negative blood donors in Nigeria. AB - BACKGROUND: Transfusion associated Hepatitis B virus (TAHBV) continues to be a major problem despite mandatory screening for Hepatitis B surface Antigen (HBsAg). Presence of HBsAg is the common method for detecting hepatitis B infection. Unfortunately, this marker is not detected during the window period of the infection. Nigeria being a developing country cannot afford DNA testing of all collected units of blood which serve as the only possibility of achieving zero risk of transfusion associated HBV. Five different serological makers of hepatitis B virus (HBV) infection were therefore assessed to evaluate the reliability of using HBsAg marker alone in diagnosis of HBV infection among blood donors and to detect the serological evidence of the infection at the window period. This will preclude the possibility of transmitting hepatitis B through transfusion of Hepatitis B surface antigen (HBsAg) negative blood in Nigeria. METHODS: Between July and August 2009, 92 blood donors were enrolled for the study. The prevalence of 5 different markers of Hepatitis B virus infection was detected using Enzyme Linked Immunosorbent Assay (ELISA). Demographic factors were assessed during the study. RESULTS: HBsAg and its antibody (anti-HBs) was detected in 18 (19.6%) and 14(15.2%) of the 92 blood donors respectively. Anti HBc IgM was found in 12(13.0%) of the 92 blood donors while Hepatitis B envelope antigen (HBeAg) and its antibody (anti-HBe) were detected in 4(8.9%) and 12(26.7%) respectively from 45 donors sampled. HBeAg is a marker of high infectivity and appears after HBsAg. At least one serological marker was detected in 30(32.6%) of the blood donors. Five (5.4%) of the 92 donors had anti-HBc IgM as the only serological evidence of hepatitis B virus infection. CONCLUSIONS: The result of this study shows that five donors have anti-HBcIgM as the only serological evidence of HBV infection. Inclusion of anti-HBcIgM in routine screening of blood donors in Nigeria should be encouraged. This is the first study to assess anti-HBcIgM in the country. PMID- 22074049 TI - Recognition of physical deterioration in patients with mental health problems: the role of simulation in knowledge and skill development. AB - Recognition of physical deterioration in patients with mental health problems has been recognized as a significant problem. Areas of particular concern include rapid tranquilization, physical restraint, the consumption of alcohol and illicit drugs have the potential to result in sudden and catastrophic patient deterioration. Simulation sessions, using patient mannequins, are widely used to support the education of nurses but its use in mental health has been somewhat restricted. The aim of this study was to design and deliver simulation scenarios to develop the skills and knowledge of mental health nursing students in the recognition and management of physical deterioration. A series of three scenarios were developed and delivered to a group of final-year nursing students. Evaluation of the sessions was undertaken using analysis of video footage from the sessions and through two focus groups. The results show that simulation is a useful catalyst for discrepancy creation which in turn leads to the student focusing their future learning towards addressing any identified deficits in skills and knowledge identified. Authenticity of the simulation sessions also plays a role in ensuring student engagement and faculty support during sessions is vital to support the students in managing unfamiliar situations. PMID- 22074050 TI - The degradative inventory of the cell: proteomic insights. AB - SIGNIFICANCE: Protein degradation has been identified as being deregulated in numerous human diseases. Hence, proteins involved in proteasomal as well as lysosomal degradation are regarded as interesting potential drug targets and are thoroughly investigated in clinical studies. RECENT ADVANCES: Technical advances in the field of quantitative mass spectrometry (MS)-based proteomics allow for detailed investigations of protein degradation dynamics and identifications of responsible protein-protein interaction networks enabling a systematic analysis of the degradative inventory of the cell and its underlying molecular mechanisms. CRITICAL ISSUES: In the current review we outline recent technical advances and their limitations in MS-based proteomics and discuss their use for the analysis of protein dynamics involved in degradation processes. FUTURE DIRECTIONS: In the next years the analysis of crosstalk between different posttranslational modifications (PTMs) will be a major focus of MS-based proteomics studies. Increasing evidence highlights the complexity of PTMs with positive and negative feedbacks being discovered. In this regard, the generation of absolute quantitative proteomic data will be essential for theoretical scientists to construct predictive network models that constitute a valuable tool for fast hypothesis testing and for explaining underlying molecular mechanisms. PMID- 22074051 TI - Reviews on animal diseases recently published in other journals. PMID- 22074053 TI - Nasal resistance in Japanese elementary schoolchildren: determination of normal value. AB - CONCLUSION: Rhinomanometry is a useful method for evaluating nasal airway patency in schoolchildren, and we could confirm the validity of the results it produces. OBJECTIVE: Our purpose was to assess the validity nasal resistance measurements produced using anterior active rhinomanometry by comparing the results with those of our previous study and to determine a normal value of the nasal resistance. METHODS: Nasal resistance was measured by rhinomanometry in 852 children using the active anterior method. RESULTS: Mean nasal resistance was 0.45 +/- 0.70 Pa/cm(3)/s. Nasal diseases were noted in 358 (42%) children, and nasal condition was normal (the normal group) in 494 (58%) children. Nasal resistance was 0.57 +/ 1.05 Pa/cm(3)/s in the nasal disease group and 0.35 +/- 0.16 Pa/cm(3)/s in the normal group, showing that resistance was significantly higher in the nasal disease group. In the normal nasal groups, nasal resistance tended to be lower in the children in higher grades (first grade, 0.44 +/- 0.17 Pa/cm(3)/s; second grade, 0.37 +/- 0.11 Pa/cm(3)/s; third grade, 0.36 +/- 0.23 Pa/cm(3)/s; fourth grade, 0.36 +/- 0.14 Pa/cm(3)/s; fifth grade, 0.30 +/- 0.08 Pa/cm(3)/s; sixth grade, 0.29 +/- 0.11 Pa/cm(3)/s), and taller groups (<120 cm, 0.43 +/- 0.16 Pa/cm(3)/s; 120-130 cm, 0.37 +/- 0.19 Pa/cm(3)/s; 130-140 cm, 0.34 +/- 0.12 Pa/cm(3)/s; >140 cm, 0.28 +/- 0.09 Pa/cm(3)/s). Results similar to those seen in our previous study were obtained in each group. PMID- 22074054 TI - Turn-on fluorescence in tetraphenylethylene-based metal-organic frameworks: an alternative to aggregation-induced emission. AB - Coordinative immobilization of functionalized tetraphenylethylene within rigid porous metal-organic frameworks (MOFs) turns on fluorescence in the typically non emissive tetraphenylethylene core. The matrix coordination-induced emission effect (MCIE) is complementary to aggregation-induced emission. Despite the large interchromophore distances imposed by coordination to metal ions, a carboxylate analogue of tetraphenylethylene anchored by Zn(2+) and Cd(2+) ions inside MOFs shows fluorescence lifetimes in line with those of close-packed molecular aggregates. Turn-on fluorescence by coordinative ligation in a porous matrix is a powerful approach that may lead to new materials made from chromophores with molecular rotors. The potential utility of MCIE toward building new sensing materials is demonstrated by tuning the fluorescence response of the porous MOFs as a function of adsorbed small analytes. PMID- 22074055 TI - Complex genetics controls natural variation among seed quality phenotypes in a recombinant inbred population of an interspecific cross between Solanum lycopersicum * Solanum pimpinellifolium. AB - Seed quality in tomato is associated with many complex physiological and genetic traits. While plant processes are frequently controlled by the action of small- to large-effect genes that follow classic Mendelian inheritance, our study suggests that seed quality is primarily quantitative and genetically complex. Using a recombinant inbred line population of Solanum lycopersicum * Solanum pimpinellifolium, we identified quantitative trait loci (QTLs) influencing seed quality phenotypes under non-stress, as well as salt, osmotic, cold, high temperature and oxidative stress conditions. In total, 42 seed quality traits were analysed and 120 QTLs were identified for germination traits under different conditions. Significant phenotypic correlations were observed between germination traits under optimal conditions, as well as under different stress conditions. In conclusion, one or more QTLs were identified for each trait with some of these QTLs co-locating. Co-location of QTLs for different traits can be an indication that a locus has pleiotropic effects on multiple traits due to a common mechanistic basis. However, several QTLs also dissected seed quality in its separate components, suggesting different physiological mechanisms and signalling pathways for different seed quality attributes. PMID- 22074056 TI - The prevalence of injection-site reactions with disease-modifying therapies and their effect on adherence in patients with multiple sclerosis: an observational study. AB - BACKGROUND: Interferon beta (IFNbeta) and glatiramer acetate (GA) are administered by subcutaneous (SC) or intramuscular (IM) injection. Patients with multiple sclerosis (MS) often report injection-site reactions (ISRs) as a reason for noncompliance or switching therapies. The aim of this study was to compare the proportion of patients on different formulations of IFNbeta or GA who experienced ISRs and who switched or discontinued therapy because of ISRs. METHODS: The Swiss MS Skin Project was an observational multicenter study. Patients with MS or clinically isolated syndrome who were on the same therapy for at least 2 years were enrolled. A skin examination was conducted at the first study visit and 1 year later. RESULTS: The 412 patients enrolled were on 1 of 4 disease-modifying therapies for at least 2 years: IM IFNbeta-1a (n = 82), SC IFNbeta-1b (n = 123), SC IFNbeta-1a (n = 184), or SC GA (n = 23). At first evaluation, ISRs were reported by fewer patients on IM IFNbeta-1a (13.4%) than on SC IFNbeta-1b (57.7%; P < 0.0001), SC IFNbeta-1a (67.9%; P < 0.0001), or SC GA (30.4%; P = not significant [NS]). No patient on IM IFNbeta-1a missed a dose in the previous 4 weeks because of ISRs, compared with 5.7% of patients on SC IFNbeta-1b (P = 0.044), 7.1% of patients on SC IFNbeta-1a (P = 0.011), and 4.3% of patients on SC GA (P = NS). Primary reasons for discontinuing or switching therapy were ISRs or lack of efficacy. Similar patterns were observed at 1 year. CONCLUSIONS: Patients on IM IFNbeta-1a had fewer ISRs and were less likely to switch therapies than patients on other therapies. This study may have implications in selecting initial therapy or, for patients considering switching or discontinuing therapy because of ISRs, selecting an alternative option. PMID- 22074057 TI - Influenza viruses in Thailand: 7 years of sentinel surveillance data, 2004-2010. AB - BACKGROUND: The re-emergence of avian influenza A (H5N1) in 2004 and the pandemic of influenza A (H1N1) in 2009 highlight the need for routine surveillance systems to monitor influenza viruses, particularly in Southeast Asia where H5N1 is endemic in poultry. In 2004, the Thai National Institute of Health, in collaboration with the U.S. Centers for Disease Control and Prevention, established influenza sentinel surveillance throughout Thailand. OBJECTIVES: To review routine epidemiologic and virologic surveillance for influenza viruses for public health action. METHODS: Throat swabs from persons with influenza-like illness and severe acute respiratory illness were collected at 11 sentinel sites during 2004-2010. Influenza viruses were identified using the standard protocol for polymerase chain reaction. Viruses were cultured and identified by immunofluorescence assay; strains were identified by hemagglutination inhibition assay. Data were analyzed to describe frequency, seasonality, and distribution of circulating strains. RESULTS: Of the 19,457 throat swabs, 3967 (20%) were positive for influenza viruses: 2663 (67%) were influenza A and able to be subtyped [21% H1N1, 25% H3N2, 21% pandemic (pdm) H1N1] and 1304 (33%) were influenza B. During 2009-2010, the surveillance system detected three waves of pdm H1N1. Influenza annually presents two peaks, a major peak during the rainy season (June-August) and a minor peak in winter (October-February). CONCLUSIONS: These data suggest that March-April may be the most appropriate months for seasonal influenza vaccination in Thailand. This system provides a robust profile of the epidemiology of influenza viruses in Thailand and has proven useful for public health planning. PMID- 22074058 TI - Dissecting T-cell activation with high-resolution live-cell microscopy. AB - Results from live-cell microscopy suggest that the behaviour of isolated components of the T-cell activation machinery in vitro does not represent the reality inside cells. Understanding the cellular-scale dynamics of microcluster migration can only be accomplished by in situ observation. Developments in 'super resolution' microscopy have permitted investigators to move beyond tracking the movements of individual molecules, allowing the recognition of protein islands and nanodomains present in quiescent and active T cells. Many high-resolution techniques have their own susceptibilities to artefacts, so it is important to take a multifaceted approach to confirm results. A major challenge for the future will be to integrate all the new information into a coherent model of antigen recognition and T-cell activation. PMID- 22074060 TI - Nurses attitudes towards the importance of families in psychiatric care following an educational and training intervention program. AB - This study measures the attitudes of the psychiatric nurses, after having received an education and training intervention program (ETI-PROGRAM) in family systems nursing, towards the importance of the families in their care. Nurses' knowledge of the impact that family nursing intervention can have on family members may increase positive attitudes towards families. However, little is known about the impact that education and training intervention can have on nurses' attitudes, towards families in clinical practice. Quasi-experimental design was used to assess the change in nurses' attitudes towards families in psychiatric care after the intervention, which included a one-day seminar on the Calgary family nursing conceptual frameworks and skills training with clinical vignettes of families from psychiatry. The Families Importance in Nursing Care - Nurses' Attitude questionnaire was used to evaluate nurses' attitudes. A total of 81 nurses (65%) working in psychiatric care responded to the questionnaire. Nurses with more than 15 years of work experience were significantly more supportive of families in their care compared with less experienced nurses. Out of the 81 nurses, 52 (64%) answered the questionnaire again 14 months later. Furthermore, psychiatric nurses saw families significantly less burdensome after having participated in the ETI-PROGRAM. PMID- 22074059 TI - Randomized pilot study of cabergoline, a dopamine receptor agonist: effects on body weight and glucose tolerance in obese adults. AB - AIM: Dopaminergic hypofunction and hyperprolactinaemia have been implicated in the pathogenesis of obesity and glucose intolerance. The aim of this pilot study was to determine the efficacy of cabergoline, a dopamine receptor agonist, on body weight and glucose tolerance in obese non-diabetic persons with normal plasma prolactin levels. METHODS: This 16-week double blind, placebo-controlled pilot study randomized non-diabetic obese adults (body mass index 30-42 kg/m(2) ) to placebo or cabergoline (0.25 mg twice weekly for 4 weeks followed by 0.5 mg twice weekly for the next 12 weeks). Of 40 subjects enrolled, 29 completed 16 weeks: 16 randomized to placebo and 13 to cabergoline. All subjects were counselled on a 500 kcal/day calorie deficit diet. A 75-g oral glucose tolerance test was performed at baseline and at 16 weeks. RESULTS: As expected, prolactin levels decreased after cabergoline (p < 0.001). Weight loss was similar after placebo compared with cabergoline treatment: 1.0 vs. 1.2% body weight, respectively. Fasting glucose levels did not differ between groups after treatment, however, 90-min postprandial glucose and insulin decreased in the cabergoline group only (p = 0.029). HOMA-IR (homeostasis model of assessment) increased by 40% after placebo and 1.5% after cabergoline treatment. CONCLUSIONS: This pilot study suggests that cabergoline therapy may improve glucose tolerance independent of weight loss, however, a larger, longer term study of dopamine receptor agonist therapy in obese individuals is warranted to confirm this finding. PMID- 22074061 TI - 'I can't relate it to teeth': a qualitative approach to evaluate oral health education materials for preschool children in New South Wales, Australia. AB - BACKGROUND: Early Childhood Caries is a significant public health issue worldwide. Although much is known about the aetiology of dental caries, there is limited evidence on the understanding of caregivers on readily available early childhood oral health education materials. AIM: The purpose of this study was to record how parents cope with dental health education materials for preschool children commonly available in New South Wales, Australia. DESIGN: This qualitative study was nested within a large cohort study in South Western Sydney. English-speaking mothers (n = 24) with young children were approached for a face to-face, semi-structured interview at their homes. Two dental leaflets designed by NSW Health to give advice on monitoring young children's oral health were sent to mothers prior to the interview. Interviews were recorded and subsequently transcribed verbatim. Transcripts were analysed by interview debriefing and a thematic coding. RESULTS: Mothers generally reported that the leaflets were easy to read but noted that the information pertaining to bottle feeding was confusing. Furthermore, they were unable to understand terms such as 'fluoride' and 'fissure sealants'. Early childhood nutrition and infant teething were inadequately addressed, and mothers preferred pictorial presentations to improve their understanding of oral health. CONCLUSIONS: Producers of health education leaflets should keep the messages simple and straightforward, avoid the use of medical jargon, and use pictorial aids to improve communication with parents. PMID- 22074062 TI - Brain activity during the Clock-Drawing Test: multichannel near-infrared spectroscopy study. AB - The Clock-Drawing Test (CDT) is widely used in clinical practice for the screening of dementia. However, neural activity during real clock drawing has not been investigated due to motion artifacts. In the present study, we examined brain activity during real clock drawing using multichannel near-infrared spectroscopy (NIRS). We measured hemoglobin concentration changes in the prefrontal and temporal surface areas during clock drawing using 52-channel NIRS. Data obtained from 37 right-handed healthy volunteers were analyzed. We found significant increases in oxy-Hb in more than 96.2% of the channels (false discovery rate corrected, p < .025). The time required for CDT performance showed a negative correlation with changes in oxy-Hb in the prefrontal region (r = .529, p = .002). The mean value for oxy-Hb changes was higher in the left hemisphere in 20 subjects (54%) and in the right hemisphere in 17 subjects (46%). The NIRS/CDT combination is acceptable as a clinical tool, as the method has the advantages of direct measurement of cortical activation with high temporal resolution. Our results confirm the aspects of the CDT involving the frontal-lobe battery. PMID- 22074063 TI - Differential diagnosis of depression and Alzheimer's disease using the Cattell Horn-Carroll theory. AB - Clinical differentiation between Alzheimer's disease (AD) and depression is often difficult due to symptom overlap and similar clinical presentation. Concise and accurate diagnostic tests have been of interest for many years. Furthermore, with the continued growth of the Cattell-Horn-Carroll (CHC) theory, there has been an emergence of measures such as the Woodcock-Johnson-III Tests of Cognitive Abilities (WJ-III COG), which are being more commonly used in clinical practice yet have not been fully evaluated in terms of their efficacy in various domains of clinical practice. This study investigated the predictive and diagnostic properties of the WJ-III COG as a CHC-based test in differentiating between AD and depression in the elderly population. A discriminative function used in the study was able to correctly classify 89.02% of cases using six areas of the CHC framework. The variables that had the highest predictive weights were: long-term retrieval, fluid reasoning, processing speed, and working memory. The main implication is that a theory-based approach is crucial in the support of differential diagnosis and in decreasing the length of assessment for elderly populations. PMID- 22074064 TI - Rehearsal significantly improves immediate and delayed recall on the Rey Auditory Verbal Learning Test. AB - A repeated observation during memory assessment with the Rey Auditory Verbal Learning Test (RAVLT) is that patients who spontaneously employ a memory rehearsal strategy by repeating the word list more than once achieve better scores than patients who only repeat the word list once. This observation led to concern about the ability of the standard test procedure of RAVLT and similar tests in eliciting the best possible recall scores. The purpose of the present study was to test the hypothesis that a rehearsal recall strategy of repeating the word list more than once would result in improved scores of recall on the RAVLT. We report on differences in outcome after standard administration and after experimental administration on Immediate and Delayed Recall measures from the RAVLT of 50 patients. The experimental administration resulted in significantly improved scores for all the variables employed. Additionally, it was found that patients who failed effort screening showed significantly poorer improvement on Delayed Recall compared with those who passed the effort screening. The general clear improvement both in raw scores and T-scores demonstrates that recall performance can be significantly influenced by the strategy of the patient or by small variations in instructions by the examiner. PMID- 22074065 TI - Characteristic of cognitive decline in Parkinson's disease: a 1-year follow-up. AB - The aim of this study was to track the evolution of cognitive decline in Parkinson's disease (PD) patients 1 year after baseline testing. Thirty-three PD patients, divided according to three previously determined subgroups based on their initial cognitive performance, and a healthy comparison group were reassessed after a 1-year interval. Participants were assessed in the following five domains: Executive Function, Problem Solving, Working Memory/Attention, Memory, and Visuospatial Ability. The PD groups differed on the domains of Executive Function, Problem Solving, and Working Memory, with the most severe deficits being evident for the group that had previously shown the greatest level of impairment. Increased cognitive problems were also associated with decreased functioning in activities of daily living. The most severely impaired group had evidence of global cognitive decline, possibly reflecting a stage of preclinical dementia. PMID- 22074066 TI - An investigation of impaired scores on the frontal assessment battery in a VA population. AB - In a population of inpatients, individuals were observed to continually score in the impaired range on the Frontal Assessment Battery (FAB) without exhibiting other signs of frontal-lobe damage. Investigations were undertaken to determine if the subtest structure, demographic factors, or general cognitive functioning may be responsible for patients' poor performance on the FAB overall. Participants were inpatients at the Ann Arbor Veterans Hospital who were administered a standard neuropsychological screening battery. This battery included the FAB, among other tests, as part of regular clinical care. Included in these study analyses were 292 patients with a mean age of 67.27 years (SD = 12.41). Descriptive analyses revealed that 63.7% of patients scored in the impaired range on the FAB based on the criteria set forth by Dubois, Slachevsky, and Litvan ( 2000 ). Analyses of individual subtest performance failed to find any single test that would characterize participants' poor performance overall. Nonetheless, the total FAB score was related to age, general cognitive functioning, and premorbid estimates of intellectual functioning. The internal reliability also was found to be lower than that reported previously. While the FAB may measure frontal-lobe functions, it appears to be influenced by a multitude of other demographic and neuropsychological factors. PMID- 22074067 TI - Sensitivity of the test of memory malingering and the Nonverbal Medical Symptom Validity Test: a replication study. AB - The current investigation sought to replicate and extend the findings of Green ( in press ), which demonstrated superior sensitivity of the Nonverbal Medical Symptom Validity Test (NV-MSVT) relative to the Test of Memory Malingering (TOMM) in the detection of suboptimal effort during neuropsychological assessment. Nearly twice as many examinees failed the NV-MSVT than the TOMM. Profile analyses of the NV-MSVT demonstrated patterns suggestive of inconsistent effort in those who failed the NV-MSVT but passed the TOMM. A classification analysis employing the Word Memory Test and Medical Symptom Validity Test as external criteria for poor effort showed that the NV-MSVT is substantially more sensitive to poor effort than the TOMM and maintains an acceptable false-positive rate. Overall, results closely matched those of the Green ( in press ) study and extend the evidence that the NV-MSVT possesses better sensitivity to poor effort than the TOMM. PMID- 22074068 TI - Validation of WAIS-III four-subtest short forms in patients with traumatic brain injury. AB - In an effort to identify four-subtest Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) short forms valid for estimating Full-Scale IQ (FSIQ) among individuals with traumatic brain injury (TBI), seven tetrad versions of the WAIS III were evaluated in a convenience sample of patients referred for neuropsychological assessment (n = 176). Estimated FSIQ scores were compared to actual FSIQ scores via correlation analyses, repeated-measures analyses of variance (ANOVAs), and frequency analyses. All short form-estimated FSIQ scores correlated highly with actual scores (all rs > .91, ps < .001). Repeated-measures ANOVAs identified no significant differences between actual and short form estimated FSIQ scores for two of the seven short forms. These same two short forms had the highest percentage of scores within +/-5 points of actual FSIQ scores (75.6% and 71.6%). Thus, two tetrad versions were consistently superior to others in accuracy of estimating FSIQ; these may be helpful when time constraints or other issues necessitate use of an abbreviated battery for estimating FSIQ among individuals with TBI. PMID- 22074069 TI - Demographic and injury-related moderators of memory and achievement outcome in pediatric TBI. AB - Critical factors affecting traumatic brain injury (TBI) outcome in children and adolescents are explored with an emphasis on an examination of age at injury as a predictor of memory functioning. Age at injury and other injury-related and demographic predictors (i.e., severity, time postinjury, gender, and socioeconomic status [SES]) of memory and achievement outcome were examined in 65 children and adolescents post-TBI compared to 65 age-matched noninjured controls. Although robust findings have been found for age at injury as a general predictor of outcome, age was not found to be a significant predictor of memory functioning following pediatric TBI. Structural equation modeling suggests that the most parsimonious model of post-TBI outcome contains two causally related latent variables: one defined by gender, SES, injury severity, and age at injury, and one defined by general cognitive functioning. PMID- 22074072 TI - Guest editors' commentary: 'State of the art' in airway management in 2011. PMID- 22074073 TI - Airway research: the current status and future directions. AB - We highlight the areas we think important for future development of the subspeciality. The ultimate goal is to improve patient care and safety and to do this, we need to identify how and where episodes of harm arise. Simply continuing with current practice does not represent the best path towards our ultimate goal; objective evidence is needed to inform changes in practice. PMID- 22074074 TI - Simulating hypoxia and modelling the airway. AB - Apnoea due to airway obstruction is an ever present concern in anaesthesia and critical care practice and results in rapid development of hypoxaemia that is not always remediable by manual bag-mask ventilation. As it is often difficult or impossible to study experimentally (although some historical animal data exist), it is useful to model the kinetics of hypoxaemia following airway obstruction. Despite being a complex event, the consequences of airway obstruction can be predicted with reasonable fidelity using mathematical and computer modelling. Over the last 15 years, a number of high fidelity mathematical and computer models have been developed, that have thrown light on this important event. PMID- 22074075 TI - Hypoxia: developments in basic science, physiology and clinical studies. AB - Airway management is primarily designed to avoid hypoxia, yet hypoxia remains the main ultimate cause of anaesthetic-related death and morbidity. Understanding some of the physiology of hypoxia is therefore essential as part of a 'holistic' approach to airway management. Furthermore, it is strategically important that national specialist societies dedicated to airway management do not only focus upon the technical aspects of airway management, but also embrace some of the relevant scientific questions. There has been a great deal of research into causation of hypoxia and the body's natural protective mechanisms and responses to it. This enables us to think of ways in which we might manipulate the cellular and molecular responses to confer greater protection against hypoxia-induced tissue injury. This article reviews some of those aspects. PMID- 22074076 TI - Can we make airway management (even) safer?--lessons from national audit. AB - The Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society (NAP4) has published an extensive report examining both current practices in the United Kingdom regarding airway management during anaesthesia and the complications of airway management during anaesthesia and in intensive care units and emergency departments. The report makes more than 160 recommendations designed to improve care of patients. These recommendations have implications for individuals, departments, organisations and potentially for national policy in terms of training, standards of practice and the need for guidelines. The report also indicates several specific areas where future research might be directed. This article focuses on the implementation phase of NAP4, emphasising the importance of taking the lessons derived from NAP4 and turning them into actions to improve the safety of airway care delivered to patients, wherever in hospital this takes place. PMID- 22074077 TI - The history of anaesthetic equipment evaluation in the United Kingdom: lessons for developing future strategy. AB - Recent guidance published by the Association of Anaesthetists of Great Britain and Ireland encourages the purchase of equipment based on evidence of safety and performance. For many years, evidence of the safety and performance of anaesthetic equipment was published by various government departments and agencies. However, these schemes were gradually eroded over time such that many devices entered the market with little or no clinical evidence of their efficacy. This recently led to the Difficult Airway Society's issuing guidance to its members on how best to select new airway devices; guidance that was based on the available evidence. This article provides a short history of the evaluation of anaesthetic equipment in the United Kingdom. PMID- 22074078 TI - Difficult mask ventilation: does it matter? AB - We discuss the relevance of finding a patient's lungs difficult to ventilate by facemask during the course of anaesthetic induction. In particular, we discuss the issue of whether it is advisable or unnecessary to check the ability to ventilate by facemask before administering a neuromuscular blocking agent. In the light of advances in supraglottic airway technology it has become possible to insert these devices very soon after induction and in a wider variety of patients. Similarly, the development of videolaryngoscopes and rapidly acting drugs such as rocuronium have raised the possibility of earlier, and possibly more successful, tracheal intubation, with the potential result that mask ventilation becomes redundant. However, we conclude by reaffirming its value in airway management strategies. PMID- 22074079 TI - Supraglottic airways in difficult airway management: successes, failures, use and misuse. AB - Supraglottic airway devices (SAD) play an important role in the management of patients with difficult airways. Unlike other alternatives to standard tracheal intubation, e.g. videolaryngoscopy or intubation stylets, they enable ventilation even in patients with difficult facemask ventilation and simultaneous use as a conduit for tracheal intubation. Insertion is usually atraumatic, their use is familiar from elective anaesthesia, and compared with tracheal intubation is easier to learn for users with limited experienced in airway management. Use of SADs during difficult airway management is widely recommended in many guidelines for the operating room and in the pre-hospital setting. Despite numerous studies comparing different SADs in manikins, there are few randomised controlled trials comparing different SADs in patients with difficult airways. Therefore, most safety data come from extended use rather than high quality evidence and claims of efficacy and particularly safety must be interpreted cautiously. PMID- 22074080 TI - Evidence for benefit vs novelty in new intubation equipment. AB - A myriad of new intubation equipment has been introduced commercially since the appearance of Macintosh/Miller blades in the 1940s. We review the role of devices that are relevant to current clinical practice based on their presence in the scientific literature. The comparative performance of new vs traditional direct laryngoscopes, their complications, their use in awake intubation techniques and the prediction of unsuccessful intubation with new devices are reviewed. Manikin studies are of limited value in this area. We conclude that in both predicted and unpredicted difficult or failed intubation, carefully selected new intubation equipment has a high success rate for tracheal intubation. Ideally, such devices should be available in all settings where tracheal intubation is performed. Most importantly, experience and competence with any of the new devices are critical for their successful use in any clinical setting. PMID- 22074081 TI - Equipment and strategies for emergency tracheal access in the adult patient. AB - The inability to maintain oxygenation by non-invasive means is one of the most pressing emergencies in anaesthesia and emergency care. To prevent hypoxic brain damage and death in a 'cannot intubate, cannot oxygenate' situation, emergency percutaneous airway access must be performed immediately. Even though this emergency is rare, every anaesthetist should be capable of performing an emergency percutaneous airway as the situation may arise unexpectedly. Clear knowledge of the anatomy and the insertion technique, and repeated skill training are essential to ensure completion of this procedure rapidly and successfully. Various techniques have been described for emergency oxygenation and several commercial emergency cricothyroidotomy sets are available. There is, however, no consensus on the best technique or device. As each has its limitations, it is recommended that all anaesthetists are skilled in more than one technique of emergency percutaneous airway. Avoiding delay in initiating rescue techniques is at least as important as choice of device in determining outcome. PMID- 22074082 TI - Airway challenges in critical care. AB - Airway management in the intensive care unit is more problematic than during anaesthesia. In general, critically ill patients have less physiological reserve and complications are more common, both during the initial airway intervention (which includes risks associated with induction of anaesthesia), and later once the airway has been secured. Despite these known risks, those managing the airway of a critically ill patient, particularly out of hours, may be relatively inexperienced. Solutions to these challenging airway problems include: recognition of those patients with a potential airway problem; implementation of a plan to deal with their airway; immediate availability of a difficult airway trolley; use of capnography for every airway intervention and continuously in all ventilator-dependent patients; and appropriate training of all intensive care unit staff including use of simulation. PMID- 22074083 TI - Progress in management of the obstructed airway. AB - There is no consensus as to the ideal approach for the anaesthetic management of the adult obstructed airway and there are advocates of awake fibreoptic intubation, inhalational induction and intravenous induction techniques. This review considers the different options available for obstruction at different anatomical levels. Decisions must also be made on the urgency of the required intervention. Particular controversies revolve around the role of inhalational vs intravenous induction of anaesthesia, the use or avoidance of neuromuscular blockade and the employment of cannula cricothyroidotomy vs surgical tracheostomy. PMID- 22074084 TI - Education in airway management. AB - In airway management, poor judgment, education and training are leading causes of patient morbidity and mortality. The traditional model of medical education, which relies on experiential learning in the clinical environment, is inconsistent and often inadequate. Curriculum change is underway in many medical organisations in an effort to correct these problems, and airway management is likely to be explicitly addressed as a clinical fundamental within any new anaesthetic curriculum. Competency-based medical education with regular assessment of clinical ability is likely to be introduced for all anaesthetists engaged in airway management. Essential clinical competencies need to be defined and improvements in training techniques can be expected based on medical education research. Practitioners need to understand their equipment and diversify their airway skills to cope with a variety of clinical presentations. Expertise stems from deliberate practice and a desire constantly to improve performance with a career-long commitment to education. PMID- 22074085 TI - An evidence-based approach to airway management: is there a role for clinical practice guidelines? AB - Complications arising out of airway management represent an important cause of anaesthesia-associated morbidity and mortality. Anaesthetic practice itself can lead to preventable harm, a particular example being persistent attempts at direct laryngoscopy, that results in delay in employing alternative strategies (or devices) when intubation is difficult. When patients are injured, expert review is called upon and often concludes that airway management provided by the anaesthetists was substandard. Many training programmes do not offer their trainees structured or organised teaching in airway management and many trainees probably enter practice with limited skills to deal with difficult airways. The literature on the management of the difficult airway in anaesthesia practice (especially as it relates to new technology and salvage strategies) is expanding rapidly. New technologies and practised response algorithms may be helpful in the management of the difficult airway, reducing the potential for adverse patient outcomes. Specialist societies and national interest groups can play an important role by critically reviewing and then applying the evidence base to generate clinical practice guidelines. The recommendations contained in such guidelines should be based on the most current evidence and they should be reviewed regularly for their content and continued relevance. PMID- 22074086 TI - Surgical treatment of infective valve endocarditis in children with congenital heart disease. AB - OBJECTIVE: This study assesses surgical procedures, operative outcome, and early and intermediate-term results of infective valve endocarditis in children with congenital heart disease. METHODS: Seven consecutive children (five females, two males; mean age, 10.8 years) who underwent surgery for infective valve endocarditis between 2006 and 2010 were included in the study. The aortic and mitral valves were affected in two and tricuspid in five patients. Indications for operation included cardiac failure due to atrioventricular septal rupture, severe tricuspid valve insufficiency, and septic embolization in one, moderate valvular dysfunction with vegetations in three (two tricuspid, one mitral), and severe valvular dysfunction with vegetations in the other three patients (two tricuspid, one mitral). The pathological microorganism was identified in five patients. Tricuspid valve repair was performed with ventricular septal defect (VSD) closure in five patients. Two patients required mitral valve repair including one with additional aortic valve replacement. RESULTS: There were no operative deaths. Actuarial freedom from recurrent infection at one and three years was 100%. Early echocardiographic follow-up showed four patients to have mild atrioventricular valve regurgitation (three tricuspid and one mitral) and three had no valvular regurgitation. No leakage from the VSD closure or any valvular stenosis was detected postoperatively. CONCLUSIONS: Mitral and tricuspid valve repairs can be performed with low morbidity/mortality rates and satisfactory intermediate-term results in children with infective valve endocarditis. PMID- 22074087 TI - Evaluating remedial alternatives for an acid mine drainage stream: a model post audit. AB - A post audit for a reactive transport model used to evaluate acid mine drainage treatment systems is presented herein. The post audit is based on a paired synoptic approach in which hydrogeochemical data are collected at low (existing conditions) and elevated (following treatment) pH. Data obtained under existing, low-pH conditions are used for calibration, and the resultant model is used to predict metal concentrations observed following treatment. Predictions for Al, As, Fe, H(+), and Pb accurately reproduce the observed reduction in dissolved concentrations afforded by the treatment system, and the information provided in regard to standard attainment is also accurate (predictions correctly indicate attainment or nonattainment of water quality standards for 19 of 25 cases). Errors associated with Cd, Cu, and Zn are attributed to misspecification of sorbent mass (precipitated Fe). In addition to these specific results, the post audit provides insight in regard to calibration and sensitivity analysis that is contrary to conventional wisdom. Steps taken during the calibration process to improve simulations of As sorption were ultimately detrimental to the predictive results, for example, and the sensitivity analysis failed to bracket observed metal concentrations. PMID- 22074088 TI - Reviews on animal diseases recently published in other journals. PMID- 22074090 TI - Marital moratorium and fertility control in China. AB - Abstract Since 1949, the issue of marital postponement has been extensively discussed in China. Unlike some other means of fertility control (e.g. abortion and oral contraception), marital postponement has been welcomed with the fewest misgivings. Lately, marital postponement has also been given renewed emphasis by those outside China who see a weak link between various current national family planning programmes based on improved technology and the goal of fertility reduction. One aim of this paper is to render a comprehensive account of the marital postponement programme in China in the course of the birth control campaign during the last two decades. The second objective is to discuss the lessons that may be learned from it, and its implications for the current fertility controversy in the United States. Four general conclusions emerge from a careful analysis of the available documents: (1) in China, proponents of delayed marriage were divided on the question of how to secure its general acceptance. One issue dividing them was whether or not China's Marriage Law of 1950 should be amended in order to achieve it. Those who favoured raising the minimum legal age disagreed on the details of the presumably needed change. There is enough evidence to suggest that medical personnel were the chief advocates of compulsory postponement of marriage. The government rejected this legalistic approach and, in so doing, agreed with Chen Ta (a noted demographer) and others who sought to achieve postponement of marriage through appropriate social and economic measures. (2) Decisions to delay matrimony in different socio-cultural settings are not necessarily identical sociological phenomena. In some societies, (e.g. the United States), they may amount to no more than a course of action that enables individuals involved to realize or develop alternate goals in life. In others (e.g. China), they are literally acts of rebellion. (3) The fertility policy dispute has been carried on in a context of revolutionary change, and involved persons who have committed themselves to transforming the Chinese family. This prior commitment was mainly responsible for the relative lack of controversy about marital postponement as a means of fertility control. (4) Use of contraception is private, hidden from open view. But postponement of marriage is public and may be a source of inter-generational and interpersonal conflict. In China and other parallel situations, a decision to delay marriage is in itself against tradition. In this sense, a full-scale marital moratorium cannot but be more than a partial assault on the hold that the family has over its offspring. This must be unequivocally reflected in discussions of fertility control policy everywhere. PMID- 22074091 TI - Religious fertility differentials in Thailand, 1960. AB - Abstract Although the evidence supporting high fertility in Thailand is clear cut, little is known about fertility differentials within the population. As part of a larger investigation, a special 1 % tabulation of the 1960 Thai census data on number of children ever-born to married women has been analysed to determine the extent of differentials by religion and urban-rural status. The findings point to considerable differentials among Buddhists, Moslems, and Confucianists. Standardizing for age, the number of children ever-born to 12/loslems averaged well below the number born to Buddhists. Confucian fertility was intermediate. Within specific age groups, the number of children ever-born to Moslem women was considerably below the Buddhist average and the differentials were sharper in the higher age groups. By contrast, Confucian fertility was highest of all in the age groups under 35, but lower than the Buddhist averages among older women. Significant urban-rural differentials also exist. For both the Buddhist and the Confucian women, fertility is markedly lower in urban than in rural categories. When controlling for both age and urban-rural status, Buddhist and Confucian differences tend to be minimal. By contrast, Moslem fertility was highest in the most urban category - Bangkok - but was considerably lower and substantially below the fertility levels of Buddhists and Confucianists in all other urban rural categories. The census data in themselves do not permit adequate analysis of the reasons for the differentials. Later age at marriage in urban places may be a significant factor in accounting for the overall differentials in urban rural fertility ; but this relation is much less clear for specific religious groups, particularly since Moslems marry at a considerably earlier age. More frequent divorce and remarriage may lower Moslem rates. Poorer health may also be a factor. PMID- 22074092 TI - Family planning in Taiwan, Republic of China: Progress and prospects. AB - Abstract The family planning programme in Taiwan is considered to have been most successful and has been systematically evaluated. In the light of some expressed scepticism, however, its impact on fertility will have to be carefully reviewed. The present article discusses six specific problems : How many women have accepted the Lippes loops or pills offered in the programme ? How long will the loop stay in utero ? What proportion of married women is currently wearing the loops ? What changes have occurred in the knowledge-attitude-practice (KAP) of family planning among the target population ? How many births have been prevented by the IUD programme ? And finally, How much has fertility declined ? The fertility decline in Taiwan has been accelerating since the programme started in 1964. Approximately 40% of the decline in the birth rate, from 36.3 in 1963 to 27.7 in 1969, or 8.5 points per 1,000 in six years, however, was due to changes in age structure and delayed marriage. An increasing proportion of girls of marriageable age and a possible increase in the fecundability of the population will work against the programme's objective. Concerted efforts and heavier investment are essential for the final success of the programme. PMID- 22074093 TI - Two and a half centuries of demographic history in a Bavarian village. AB - Abstract A village genealogy containing family histories of couples married between 1692 and 1939 serves as the basis for a study of the demographic history of a Bavarian village. The past patterns of marriage, re-marriage, widowhood, illegitimacy, bridal pregnancy, marital fertility, family size, and birth intervals are examined. Both the age at marriage and illegitimacy increased and then declined during the nineteenth century, apparently in response to changes in restrictive marriage legislation. Differences in fertility for occupational groups were insignificant. Marital fertility remained extremely high before 1900 suggesting the absence of any substantial family limitation within marriage. A rise in marital fertility that occurred during the last half of the nineteenth century appears to result from a change in breast-feeding customs. The actual number of children surviving to maturity for most couples was kept quite low, however, through late marriage and high infant mortality. Only during the twentieth century are substantial declines in infant mortality and fertility evident. PMID- 22074094 TI - Adam Smith on population. AB - Abstract Adam Smith dealt with questions of population mainly in his Wealth of Nations. His discussion falls roughly under five heads and reflects in considerable measure his image of the English economy. (1) A country's population capacity, given the average level of consumption, was conditioned by the stock of land, the skill with which it was cultivated, and the degree to which division of labour could be increased and thereby augment output for domestic use and sale in external markets. (2) Growth of population was essentially in response to growth of the demand for labour and served to increase division of labour. (3) The social mechanisms underlying elevation of the scale of living are touched upon, and in an optimistic spirit. (4) The distribution of a country's population responded to its progress in opulence, with the rate of this progress conditioned by the degree to which inappropriate (e.g. mercantilist) policies were avoided. (5) Smith dealt briefly with such matters as colonies, education, size of economy, environmental influences, and public policy, all of which he recognized as significant for the quantity and quality of a country's numbers. PMID- 22074095 TI - Pre-marital pregnancy, childspacing, and later economic achievement. AB - Abstract The nature of the first-birth interval has a persistent, if diminishing relation to the family's economic position at successive observations in a longitudinal study of Detroit. The pre-maritally pregnant (PMP) were at a disadvantage at either the first (1961) observation or the fourth (1966) as compared with other married couples with either a short or long first birth interval (short-spacers and long-spacers). The PMP disadvantage was much greater for assets than for income, but disadvantage in each area persisted and was not a result of age, duration of marriage, or other factors likely to disappear in time. Poor education combined with early age at marriage was probably responsible. On the other hand, the economic disadvantages of the short-spacers (not PMP) as compared with the long-spacers, diminished consistently between 1961 and 1965. The initial disadvantage results from shorter marriage and career duration for husbands at each parity. At comparable marriage durations the difference disappears. Nevertheless, this means substantially smaller resources per head at the actual time of birth of successive children. PMID- 22074096 TI - Nineteenth-Century fertility oscillations. AB - Abstract A model of delayed response, developed within the frame of a general sociological analysis, is applied to oscillations in aggregate legitimate fertility, considered as delayed responses to variations in the marriage rate. The appropriate lag function is derived on the basis of an assumed fertility schedule by duration of marriage. It is shown that if oscillations were caused solely by marriage fluctuations they would be very smooth with an 'average period' of 25 years and upwards. In Swedish data from the period 1830-1879 this smooth pattern is discernible as one component, overlaid by short-term fluctuations for which some other cause must be found. After a discussion of alternative explanations it is submitted that the cause is the practice of birth control on a fairly extensive scale, long before the secular decline in marital fertility, a conclusion which ties in with the results of earlier analyses of nineteenth-century fertility. PMID- 22074097 TI - The spread of urbanization in England and Wales, 1851-1951. AB - Abstract Each county in England and Wales has been classified as rural or urban for each of the decennial census years 1851-1951. One index has been used as the basis for these classifications, the percentage of adult males occupied in agriculture. Thus, for each census year a value, in term of this index, was fixed as the criterion to determine whether a county was rural or urban in that year. This criterion of classification varies, over time. This is to allow for the reduction in the percentage of adult males occupied in agriculture as a result of structural changes in the occupational distribution (associated with general modernization), rather than through a shift away from agriculture. The geographical patterns of urbanization in England and Wales during the period 1851 1951, and some associated social and economic changes, are discussed in the paper. PMID- 22074099 TI - "The decline of the size of the domestic group in England". PMID- 22074098 TI - Size and structure of the household in England over three centuries: A comment. PMID- 22074100 TI - Economic value of preventing births: Reply to Simon. PMID- 22074103 TI - Prevalence of human papillomavirus infection in women in Benin, West Africa. AB - BACKGROUND: Cervical cancer ranks as the first most frequent cancer among women in Benin. The major cause of cervical cancer now recognized is persistent infection of Human Papillomavirus (HPV). In Benin there is a lack of screening programs for prevention of cervical cancer and little information exists regarding HPV genotype distribution. METHODS: Cervical cells from 725 women were examined for the presence of viral DNA by means of a polymerase chain reaction (PCR) multiplex-based assay with the amplification of a fragment of L1 region and of E6/E7 region of the HPV genome, and of abnormal cytology by Papanicolaou method. The association between HPV status and Pap test reports was evaluated. Socio-demographic and reproductive characteristics were also related. RESULTS: A total of 18 different HPV types were identified, with a prevalence of 33.2% overall, and 52% and 26.7% among women with and without cervical lesions, respectively. Multiple HPV infections were observed in 40.2% of HPV-infected women. In the HPV-testing group, the odds ratio for the detection of abnormal cytology was 2.98 (95% CI, 1.83-4.84) for HPV positive in comparison to HPV negative women. High risk types were involved in 88% of infections, most notably HPV-59, HPV-35, HPV-16, HPV-18, HPV-58 and HPV-45. In multiple infections of women with cytological abnormalities HPV-45 predominated. CONCLUSIONS: This study provides the first estimates of the prevalence of HPV and type-specific distribution among women from Benin and demonstrates that the epidemiology of HPV infection in Benin is different from that of other world regions. Specific area vaccinations may be needed to prevent cervical cancer and the other HPV-related diseases. PMID- 22074104 TI - Targeted quantitative phosphoproteomics approach for the detection of phospho tyrosine signaling in plants. AB - Tyrosine (Tyr) phosphorylation plays an essential role in signaling in animal systems. However, a few studies have also reported Tyr phosphorylation in plants, but the relative contribution of tyrosine phosphorylation to plant signal transduction has remained an open question. We present an approach to selectively measure and quantify Tyr phosphorylation in plant cells, which can also be applied to whole plants. We combined a (15)N stable isotope metabolic labeling strategy with an immuno-affinity purification using phospho-tyrosine (pY) specific antibodies. This single enrichment strategy was sufficient to reproducibly identify and quantify pY containing peptides from total plant cell extract in a single LC-MS/MS run. We succeeded in identifying 149 unique pY peptides originating from 135 proteins, including a large set of different protein kinases and several receptor-like kinases. We used flagellin perception by Arabidopsis cells, a model system for pathogen triggered immune (PTI) signaling, to test our approach. We reproducibly quantified 23 pY peptides in 2 inversely labeled biological replicates identifying 11 differentially phosphorylated proteins. These include a set of 3 well-characterized flagellin responsive MAP kinases and 4 novel MAP kinases. With this targeted approach, we elucidate a new level of complexity in flagellin-induced MAP kinase activation. PMID- 22074105 TI - Intra-individual assessment of speech and music perception in cochlear implant users with contralateral CochlearTM and MED-ELTM systems. AB - CONCLUSION: Whilst objective testing on music perception showed no individual differences between cochlear implant (CI) devices, subjective music perception was found to be superior with the MED-EL device in the majority of cases evaluated. OBJECTIVE: To compare speech and music perception through two different CI systems in the same individuals. METHODS: Six post-lingually deaf patients, who had been implanted with a CochlearTM Nucleus((r)) device in one ear and a MED-EL SONATATI(100) on the contralateral side were evaluated. One subject was excluded from group analysis because of significant differences in performance between ears. Subjects completed a questionnaire designed to assess implant users' listening habits. Subjective assessments of each subject were made for comparison of speech and music perception with each system and preferences of system. The subjects consecutively used each system with the contralateral device turned off, and were objectively assessed for specific musical skills. Speech perception in quiet and in noise was tested. RESULTS: For all objective tests of music discrimination and speech perception in noise, there were no statistically significant differences between MED-EL and Cochlear CI systems. Subjectively, four subjects thought their MED-EL device was better than their Cochlear device for music appreciation. Four thought that music sounded more natural, less tinny and more reverberant with their MED-EL CI than with their Cochlear CI. One subject rated all these to be equal. PMID- 22074106 TI - 15-year efficacy of uvulopalatopharyngoplasty based on objective and subjective data. AB - CONCLUSIONS: This follow-up showed a stable and significant decrease in median oxygen desaturation index 4% (ODI(4)) values over the years. Approximately two thirds of the patients fulfilled the success criteria (ODI(4) reduction of 50% and <20) after 15 years. A majority had improved/cured excessive daytime sleepiness (EDS) and were satisfied. No increased mortality rate was seen. OBJECTIVES: To evaluate sleep apnoea recordings and symptoms in patients with obstructive sleep apnoea syndrome 15 years after uvulopalatopharyngoplasty (UPPP) compared to baseline and previous follow-ups. METHODS: This was a non-randomized, prospective intervention study on 50 patients who underwent UPPP during 1985-88. Their initial median age was 49 years (range 38-71) and ODI(4) was 26.5 (4-82). RESULTS: In all, 13 patients had died; 26 patients underwent sleep apnoea recordings. Median ODI(4) had decreased from 26.5 (range 4-82) to 8.5 (0-60), p < 0.01, a mean reduction of 52%; 65% of patients achieved the success criteria. One third was objectively categorized as non-snorers. Median body mass index was unchanged. The questionnaires were answered by 32 of 37 patients; 88% reported improved or cured EDS and 78% were satisfied. Pharyngeal disturbances ratings were low. The standardized mortality rate did not differ from the general Swedish population. PMID- 22074107 TI - Efficacy of percutaneous vocal fold injections for benign laryngeal lesions: Prospective multicenter study. AB - CONCLUSION: Percutaneous steroid injection (PSI) may be a useful alternative modality for treatment of benign vocal fold lesions. OBJECTIVES: When patients refuse general anesthesia or voice therapy for benign vocal fold diseases (Reinke's edema, vocal polyp, nodule, and scarring), there are no other options available. We conducted an analysis of the effects of PSI as an alternative treatment for benign vocal fold diseases. METHODS: From October 2008 to March 2010, 130 patients with benign vocal fold disease who refused general anesthesia or showed no response to voice therapy underwent PSI. From this group, the present study included 115 patients who completed the evaluation before PSI and at the first and third month after PSI and also an additional 25 patients who completed evaluation at the sixth month after PSI. RESULTS: Among 115 patients in the study, 40 cases (34.8%) showed complete remission and 57 cases (49.6%) showed partial remission. As a result, overall improvement rates were 84.4%. Almost all objective and subjective parameters showed statistical improvement at the first and third month after PSI (p < 0.05). Jitter and all subjective parameters maintained statistical improvement until the sixth month. No severe complications, such as fold atrophy, were observed. PMID- 22074108 TI - HBV inhibits apoB production via the suppression of MTP expression. AB - BACKGROUND: Liver dominates the production and secretion of apolipoprotein B (apoB) and evidence shows that liver malfunction induced by hepatitis B virus (HBV) infection could lead to apolipoprotein metabolism disorders. The present study was undertaken to assess the effects of HBV on apoB expression. METHODS: Clinical examination: serum apoB levels in patients with chronic HBV infection and in healthy individuals were measured by immunoturbidimetry using biochemical analyzer Olympus 5400. Cell study: mRNA and protein expression levels of apoB in HepG2 and HepG2.2.15 cells were measured by RT-PCR and Western blot. Alternatively, HBV infectious clone pHBV1.3 or control plasmid pBlue-ks were tranfected into HepG2 cells, and mRNA and protein expression levels of apoB, as well as the microsomal triglyceride transfer protein (MTP) in tranfected HepG2 cells were also measured by RT-PCR and western blot. RESULTS: Serum apoB level was much lower in chronic HBV patients as compared to healthy individuals (P < 0.05). Expression of apoB mRNA and protein was lower in HepG2.2.15 cells than in HepG2 cells. Similarly, expression of apoB mRNA and protein was lower in pHBV1.3 transfected HepG2 cells than in pBlue-ks transfected HepG2 cells. Expression of MTP mRNA and protein in pHBV1.3 transfected HepG2 cells was reduced in a dose dependent fashion. CONCLUSION: HBV infection plays an inhibitory effect on apoB expression. PMID- 22074109 TI - Smoking in preeclamptic women is associated with higher birthweight for gestational age and lower soluble fms-like tyrosine kinase-1 levels: a nested case control study. AB - BACKGROUND: Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers. METHODS: From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit. RESULTS: In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (beta = -0.29; p = 0.008, and beta = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (beta = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054). CONCLUSIONS: Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti angiogenic protein sFlt-1. PMID- 22074110 TI - Prognostic significance of hemoglobin A1c level in patients hospitalized with coronary artery disease. A systematic review and meta-analysis. AB - BACKGROUND: The prognostic value of hemoglobin A1c (HbA1c) in coronary artery disease (CAD) remains controversial. Herein, we conducted a systematic review to quantify the association between elevated HbA1c levels and all-cause mortality among patients hospitalized with CAD. METHODS: A systematic search of electronic databases (PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to May 2011 was performed. Cohort, case-control studies, and randomized controlled trials that examined the effect of HbA1c on all-cause mortality were included. RESULTS: Twenty studies met final inclusion criteria (total n = 13, 224). From the pooled analyses, elevated HbA1c level was significantly associated with increased short-term (OR 2.32, 95% CI, 1.61 to 3.35) and long-term (OR 1.54, 95% CI, 1.23 to 1.94) mortality risk. Subgroup analyses suggested elevated HbA1c level predicted higher mortality risk in patients without diabetes (OR 1.84, 95% CI, 1.51 to 2.24). In contrast, in patients with diabetes, elevated HbA1c level was not associated with increased risk of mortality (OR 0.95, 95% CI, 0.70 to 1.28). In a risk-adjusted sensitivity analyses, elevated HbA1c was also associated with a significantly high risk of adjusted mortality in patients without diabetes (adjusted OR 1.49, 95% CI, 1.24 to 1.79), but had a borderline effect in patients with diabetes (adjusted OR 1.05, 95% CI, 1.00 to 1.11). CONCLUSIONS: Our findings demonstrate that elevated HbA1c level is an independent risk factor for mortality in CAD patients without diabetes, but not in patients with established diabetes. Prospective studies should further investigate whether glycemic control might improve outcomes in CAD patients without previously diagnosed diabetes. PMID- 22074112 TI - Personal identification by the comparison of facial profiles: testing the reliability of a high-resolution 3D-2D comparison model. AB - Identification from video surveillance systems is frequently requested in forensic practice. The "3D-2D" comparison has proven to be reliable in assessing identification but still requires standardization; this study concerns the validation of the 3D-2D profile comparison. The 3D models of the faces of five individuals were compared with photographs from the same subjects as well as from another 45 individuals. The difference in area and distance between maxima (glabella, tip of nose, fore point of upper and lower lips, pogonion) and minima points (selion, subnasale, stomion, suprapogonion) were measured. The highest difference in area between the 3D model and the 2D image was between 43 and 133 mm(2) in the five matches, always greater than 157 mm(2) in mismatches; the mean distance between the points was greater than 1.96 mm in mismatches, <1.9 mm in five matches (p < 0.05). These results indicate that this difference in areas may point toward a manner of distinguishing "correct" from "incorrect" matches. PMID- 22074111 TI - SKP1 is involved in abscisic acid signalling to regulate seed germination, stomatal opening and root growth in Arabidopsis thaliana. AB - Abscisic acid (ABA) regulates many aspects of plant development, including seed dormancy and germination, root growth and stomatal closure. Plant SKP1 proteins are subunits of the SCF complex E3 ligases, which regulate several phytohormone signalling pathways through protein degradation. However, little is known about SKP1 proteins participating in ABA signalling. Here, we report that the overexpression of Triticum aestivum SKP1-like 1 (TSK1) in Arabidopsis thaliana (Arabidopsis) resulted in delayed seed germination and hypersensitivity to ABA. The opening of stomatal guard cells and the transcription of several ABA responsive genes were affected in transgenic plants. In contrast, Arabidopsis skp1-like 1 (ask1)/ask1 ASK2/ask2 seedlings exhibited reduced ABA sensitivity. Furthermore, the transcription of ASK1 and ASK2 was down-regulated in abi1-1 and abi5-1 mutants compared with that in wild type. ASK1 or ASK2 overexpression could rescue or partially rescue the ABA insensitivity of abi5-1 mutants, respectively. Our work demonstrates that SKP1 is involved in ABA signalling and that SKP1-like genes may positively regulate ABA signalling by SCF-mediated protein degradation. PMID- 22074113 TI - Excited state proton transfer is not involved in the ultrafast deactivation of Guanine-Cytosine pair in solution. AB - Different derivatives of Guanine (G) and Cytosine (C), which sterically enforce the Watson-Crick (WC) conformer, have been studied in CHCl(3) by means of broad band transient absorption spectroscopy. Our experiments rule out the involvement of an Excited State Proton Transfer (ESPT), which dominates the excited state decay of GC in the gas phase. Instead, the ultrafast dynamics via internal conversion occurs in a polar environment mainly by relaxation in the monomer moieties. Time-dependent density functional theory (TD-DFT) calculations in solution indeed indicate that population transfer from the bright excited states toward the charge transfer state is not effective in CHCl(3) and a noticeable energy barrier is associated with the ESPT reaction. ESPT is therefore not expected to be a main deactivation route for GC pairs within DNA. PMID- 22074114 TI - p62 at the interface of autophagy, oxidative stress signaling, and cancer. AB - SIGNIFICANCE: Sequestosome 1 (p62/SQSTM1) is a multifunctional adapter protein implicated in selective autophagy, cell signaling pathways, and tumorigenesis. RECENT ADVANCES: Recent evidence has revealed that p62/SQSTM1 has a critical role in an oxidative stress response pathway by its direct interaction with the ubiquitin ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), which results in constitutive activation of the transcription factor NF-E2-related factor 2 (NRF2). CRITICAL ISSUES: Both NRF2 and KEAP1 are frequently mutated in cancer. The findings just cited uncover a link between p62/SQSTM1, autophagy, and the KEAP1-NRF2 stress response pathway in tumorigenesis and shed light on the interplay between autophagy and cancer. FUTURE DIRECTIONS: Here, we review the mechanisms by which p62/SQSTM1 implements its multiple roles in the regulation of tumorigenesis with emphasis on the KEAP1-NRF2 stress response signaling pathway. Uncovering the molecular mechanisms of p62/SQSTM1 function in oxidative stress signaling might contribute to elucidating its role in tumorigenesis. PMID- 22074115 TI - Sensitive detection and accurate monitoring of Plasmodium vivax parasites on routine complete blood count using automatic blood cell analyzer (DxH800(TM)). AB - INTRODUCTION: Plasmodium vivax malaria is one of the most important infectious diseases plaguing humanity and causes significant mortality and morbidity worldwide. The gold standard of P. vivax malaria diagnosis is the microscopy of blood smears. Although microscopy is a rapid, cost-effective, and readily applicable method, it has many disadvantages, including low sensitivity, specificity, and precision. Therefore, there is a clear need for an effective screening test for P. vivax malaria detection both in high-prevalence areas and developed countries. METHODS: A total of 1761 complete blood count (CBC) samples generated by the automated hematology analyzer (DxH 800TM; Beckman Coulter Inc., Miami, FL, USA) were retrospectively analyzed. The sample pool contained 123 samples from 52 P. vivax malaria patients and 1504 nonmalarial samples including 509 patients with leukopenia (white blood cell <2000/MUL) and 134 normal subjects. RESULTS: The P. vivax malaria samples exhibited easily recognizable typical malaria signals on the nucleated red blood cell (nRBC) plots (sensitivity 100%) in DxH 800TM. All 1504 samples without P. vivax infection were negative for malaria signal (specificity 100%). The size of P. vivax malaria signals correlated roughly with the parasite burden. CONCLUSION: DxH800TM provides very sensitive and specific, easily recognizable P. vivax malaria signals on routine CBC without need for the additional reagents or special procedures. PMID- 22074116 TI - Daily life for young adults who care for a person with mental illness: a qualitative study. AB - This study describes the daily life and management strategies of young informal carers of family members or friends with mental illness. Twelve young adults (three men and nine women; 16-25 years old) in Sweden were voluntarily recruited between February and May 2008. Data collected through eight individual semi structured interviews and one focus group interview were analysed using qualitative content analysis. The findings revealed nine subthemes that were further grouped into three main themes: showing concern, providing support and using management strategies. Participants lived in constant readiness for something unexpected to happen to the person they cared for, and their role in the relationship could change quickly from family member or friend to guardian or supervisor. Supporting a friend was considered as large a personal responsibility as supporting a family member. Their management strategies were based on individual capacities and their ability to step aside should the situation become too demanding. These young informal carers need support in caring for the mentally ill. As the internet becomes increasingly fundamental to daily life, support could be provided most effectively through person-centred web sites. PMID- 22074117 TI - Fast dissolving beta-lapachone particles and tablets: an approach using surface adsorption technique. AB - BACKGROUND: beta-lapachone (betaLAP) is obtained from natural resources with promising preliminary results against the etiologic agent of Chagas disease. betaLAP activity is associated with generation of free radical and inhibition of nucleic acids and protein synthesis leading an outstanding antichagasic action. Low water solubility and large therapeutic doses constitute the main problems to overcome in the development of dosage forms of this drug. OBJECTIVE: The purpose of the present research was to enhance the limited dissolution rate of betaLAP by promoting the spontaneous crystalline growth of betaLAP on the surface of an inert excipient. METHODS: Physicochemical characterization of the particles was carried out as well as the drug dissolution rate. Drug adsorbed particles were compared to the drug as supplied and its physical mixtures with the inner excipient. The utility of the betaLAP adsorbed particles in the development of tablets obtained by direct compression were also evaluated. RESULTS: Particles produced by spontaneous crystalline growth of betaLAP on microcrystalline cellulose (MCC) hydrophilic surface showed mean diameters between 55-65 um and fast drug dissolution rate (90% drug dissolved at 50 min). Neither physical nor chemical instability of the drug were detected after the drug adsorption procedure. The compression process does not extensively deteriorate the dissolution behaviour of the systems when an adequate compression pressure is used. CONCLUSIONS: Surface adsorption technique offers a simple way to produce betaLAP powder and tablets with improved dissolution rate for oral administration. PMID- 22074118 TI - A novel tactile-guided detection and three-dimensional localization of clinically significant breast masses. AB - This paper presents a novel robotic sensory system 'Robo-Tac-BMI', which manipulates an indentation probe for the detection and three-dimensional localization of an abnormal mass embedded in the breast tissue. The Robo-Tac-BMI is designed based on artificial tactile sensing technology which is a new non invasive method for mimicking the surgeon's palpation quantitatively. The intelligent processor of the device provides an overall stiffness map of the scanned areas. The extracted stiffness parameters provide a decisive factor for certifying the mass existence. Results are validated by 'gold standard' tests. Following the mass detection, its 3D localization is of essential importance in the treatment procedures. The planar 2D coordinate is readily available for all points on the tissue surface. Mass depth estimation is achieved by a comprehensive model utilizing the logistic regression algorithm and a Receiver Operating Characteristic (ROC) Curve for the highest accuracy. Statistical analysis is performed over 27 cases with 346 scanned areas. PMID- 22074119 TI - Biomimetic polymersomes as carriers for hydrophilic quantum dots. AB - For polymersomes to achieve their potential as effective delivery vehicles, they must efficiently encapsulate therapeutic agents into either the aqueous interior or the hydrophobic membrane. In this study, cell membrane-mimetic polymersomes were prepared from amphiphilic poly(D,L-lactide)-b-poly(2 methacryloyloxyethylphosphorylcholine) (PLA-b-PMPC) diblock copolymers and were used as encapsulation devices for water-soluble molecules. Thioalkylated zwitterionic phosphorylcholine protected quantum dots (PC@QDs) were chosen as hydrophilic model substrates and successfully encapsulated into the aqueous polymersome interior, as evidenced by transmission electron microscopy (TEM) and flow cytometry. In addition, we also found a fraction of the PC@QDs were bound to both the external and internal surfaces of the polymersome. This interesting immobilization might be due to the ion-pair interactions between the phosphorylcholine groups on the PC@QDs and polymersomes. The experimental encapsulation results support a mechanism of PLA-b-PMPC polymersome formation in which PLA-b-PMPC copolymer chains first form spherical micelles, then worm-like micelles, and finally disk-like micelles which close up to form polymersomes. PMID- 22074120 TI - Training mental health promotion workers in programme evaluation. AB - In this paper, a programme to train mental health promotion workers in programme evaluation is described and evaluated. The programme is based on adult learning values, guidelines for programme evaluation training and the general principles of mental health promotion. Facilitated over 2 days, the programme also provided individual mentoring. Training was evaluated via a questionnaire immediately before and post training, and 6 months post training (n = 28, n = 18, n = 18). Additionally, individual interviews were used with seven participants and qualitatively analysed. Results indicate significant and sustained positive changes in knowledge, confidence and behaviour and while satisfaction reduced significantly at the six month follow-up, participants' level of satisfaction towards mentoring was consistent. Post training, participants reported a greater appreciation of the importance of evaluation planning and working collaboratively. PMID- 22074121 TI - Associations of miRNA polymorphisms and female physiological characteristics with breast cancer risk in Chinese population. AB - mircoRNAs (miRNAs) play important roles on regulation of gene expressions. Aberrant expression of miRNAs was involved in various biological and pathological processes, including tumorigenesis of breast cancer. Single-nucleotide polymorphisms (SNPs) were implicated in altered expression or biological functions of mature miRNAs. To explore the relevance of miRNA polymorphisms and female physiological characteristics to breast cancer risk, SNPs located within hsa-miR-605 (rs2043556), hsa-miR-149 (rs2292832), hsa-miR-27a (rs895819), hsa-miR 196a-2 (rs11614913) and hsa-miR-618 (rs2682818) were selected, and their associations with breast cancer risk were analysed. In addition, associations between physiological characteristics-related factors and breast cancer risk were estimated too. We found that the ones with menarche age less than 16 years had increased breast cancer risk (OR = 2.10, 95% CI: 1.23-3.60). Marginally significant association between rs11614913 CT/CC genotypes and reduced breast cancer risk was observed (OR = 0.65, 95% CI: 0.40-1.06), while no significance was detected about the other miRNA polymorphisms. We concluded that menarche at less than 16 years old increased breast cancer risk, while the genetic variants in miR-196-a-2 might decrease the risk. PMID- 22074122 TI - Effects of aliskiren on QT duration and dispersion in hypertensive patients with type 2 diabetes mellitus. AB - AIM: To evaluate the effect of aliskiren compared to amlodipine on QT duration and dispersion in hypertensive patients with type 2 diabetes. METHODS: A total of 170 outpatients aged 50-75 years with mild to moderate hypertension (SBP >130 and <180 mmHg and DBP >80 and <100 mmHg) and type 2 diabetes were randomly treated with aliskiren 300 mg or amlodipine 10 mg, both given once daily for 24 weeks, according to a prospective, open label, blinded-end point, parallel group design. At the end of the placebo run-in, and after 12, and 24 weeks of treatment blood pressure (BP) measurements (by mercury sphygmomanometer, Korotkoff I and V), plasma biochemistry and a standard 12-lead surface ECG were evaluated. RESULTS: Both aliskiren and amlodipine significantly reduced systolic blood pressure (SBP)/diastolic blood pressure (DBP) values (-27.2/-14.3 mmHg, p < 0.001 vs. placebo and -27.8/-14.2 mmHg, p < 0.001 vs. placebo, respectively), with no statistical difference between the two drugs. Aliskiren, but not amlodipine, significantly reduced maximum QT interval (QTmax) (-14 ms at 12 weeks and -17 ms at 24 weeks, both p < 0.05 vs. placebo) and corrected QT max (QTc max) (-26 ms and -31 ms, p < 0.01) as well as the dispersion of both QT (-11 ms and -13 ms, p < 0.01) and QTc (-18 ms and -19 ms, p < 0.01). CONCLUSIONS: Despite similar BP lowering effect, aliskiren, but not amlodipine, reduced QT duration and dispersion, which might be related to the ability of aliskiren to interfere with mechanisms underlying myocardial electrical instability in the heart of diabetic hypertensive patients. PMID- 22074123 TI - alpha-Thalassemia syndromes in the United Arab Emirates. AB - alpha-Thalassemia (alpha-thal) is usually due to deletions within the alpha globin gene cluster, leading to loss of function of one or both alpha-globin genes. alpha-Thalassemia is prevalent in the Arabian Peninsula, particularly in the United Arab Emirates (UAE) and Saudi Arabia. There are no large-scale reports regarding the prevalence of alpha-thal in the Arabian populations apart from sporadic surveys in the mid-1980s on red cell indices from Saudi Arabia and a more recent study from Kuwait. Several studies were conducted in an attempt to elucidate the frequency of alpha-thal in the UAE. Cord blood samples were collected from 419 consecutive newborns of UAE national mothers. The study involved polymerase chain reaction (PCR)-based analysis of the alpha-globin genes and sequencing using an ABI Genetic Analyser 3130. The findings demonstrated that 49% of the neonates had alpha-thal, one of the highest in the world. The incidence of alpha-thal, particularly the -alpha(3.7) deletion, was extremely high. The distribution of mutations was extensive, ranging from the simple alpha(3.7) genotype to severe nondeletional type alpha-thalassemias such as the polyadenylation signal (polyA1) [alpha(PA-1) (AATAAA>AATAAG)], polyA2 [alpha(PA 2) (AATAAA>AATGAA)], Hb Constant Spring [Hb CS, alpha142 (alpha(CS)alpha/alpha(CS)alpha) TAA>CAA (alpha2)] and pentanucleotide deletion [alpha(-5 nt) (GAGGTGAGG>GAGG)]. The nondeletional mutations, denoted alpha(T)alpha or alphaalpha(T), are markedly frequent in the UAE and are well characterized. The report here describes the analysis of 84 chromosomes having deletional and nondeletional types of alpha-thal. Of the 84 chromosomes, 47.4% had the polyA1 mutation (alpha(PA-1)alpha), 28.2% had the small deletion alpha(3.7), 11.5% had Hb CS (alpha(CS)alpha), and 5% were positive for the pentanucleotide deletion (alpha(-5 nt)alpha). These findings show that nondeletional alpha-thal has a significant impact on the genotype/phenotype correlation in the UAE. It is important to note that the polyA1 mutation accounted for almost 50% of all the alpha-thal alleles, making it one of the most common mutations in the Gulf Region. PMID- 22074124 TI - Molecular basis of beta-thalassemia in the United Arab Emirates. AB - In an attempt to define the prevalence of beta-thalassemia (beta-thal) in the United Arab Emirates (UAE), we have conducted molecular studies on nearly 2000 randomly-selected adult UAE nationals. The results demonstrated that the prevalence of beta-globin gene defects in the UAE was 8.5%. Among these anomalies were beta-thal mutations, abnormal hemoglobin (Hb) variants, e.g., Hb S, Hb D Punjab, Hb O-Arab, Hb C and Hb E. The sickle gene (beta(S) or Hb S) contributed significantly to the molecular epidemiology of the hemoglobinopathies in the UAE. In this article, Hb S and other abnormal Hbs are excluded as they are comprehensively described by other contributors in this current issue. The molecular characterization and mutational analyses of all beta-thal patients were carried out using current molecular techniques including amplification refractory mutation system (ARMS), restriction enzyme analysis (REA), dot-blot hybridization, beta-strip hybridization, allele-specific oligonucleotide (ASO), polymerase chain reaction (PCR), gap-PCR and DNA Sequencing. Most of these techniques are now virtually obsolete. Almost all molecular characterizations are currently performed through PCR followed by DNA sequencing using a fully automated ABI PRISMTM 3130 Genetic Analyzer. Our molecular studies showed that the majority of the beta-thal mutations in the UAE are very severe; the most common allele was the IVS-I-5 (G>C). Although this allele is a beta(+)-thal, its phenotype is very severe. All other mutations are also severe beta(0)-thal. High frequency of moderate or severe beta-thal mutations have implications in the wide spectrum of clinical manifestations seen in patients whose phenotypes vary from beta-thal intermedia (beta-TI) to severe transfusion-dependent beta-thal major (beta-TM). The molecular pathology of the beta-thal patients demonstrated that a vast majority were homozygous. The most frequent homozygous mutation was the IVS I-5(G>C)/IVS-I-5(G>C) (53.0%) followed by -25 bp del/-25 bp del (6.8%), codons 8/9(+G)/codons 8/9(+G) (2.8%) and codon 39(C>T)/codon 39(C>T) (2.4%). Four mutations accounted for 65.0% of the homozygous patient population. Remarkably, the two most prevalent mutations, IVS-I-5 and Hb S, accounted for 77% of all the homozygous beta-thal patients from the UAE. We showed 13 discrete homozygosities in the UAE national patients in contrast to 23 homozygosities in the expatriate population. Since the number of homozygous mutations has a direct correlation with the degree of consanguinity, the data shown here corroborate the social tendency towards family planning. In fact, in the UAE, more than 50% of all marriages are between relatives and more than half of these are between first cousins. PMID- 22074125 TI - Use of hormone replacement therapy for correction of high turnover bone disease in hypogonadal beta-Thalassemia major patients presenting with osteoporosis: comparison with idiopathic premature ovarian failure. AB - Osteopenia-osteoporosis syndrome (OOS) causes considerable morbidity in 60-80% beta-thalassemia major (beta-TM) patients. We evaluated the effect of sex hormone replacement therapy (HRT) in beta-TM patients with hypogonadism presenting with OOS using premature ovarian failure (POF) for comparative purposes. We undertook a 10-year prospective study of in 50 beta-TM and 375 patients with POF and OOS. All were treated with HRT for 2-5 years. We used dual X-ray absorptiometry (DEXA), and plasma type 1-collagen markers of bone turnover for monitoring of response to therapy. Our results suggest that prior to HRT, both groups had comparable degrees of OOS. Both groups had significant improvement but the POF group had normalization of spinal T scores following HRT in contrast to the beta TM patients. Femoral T scores did not normalize in both groups. These data indicate for the first time from comparative POF control studies that hypogonadism is not the only cause of OOS in beta-TM. PMID- 22074126 TI - Sex steroid priming for induction of puberty in thalassemia patients with pulsatile reversible hypogonadotrophic hypogonadism. AB - Growth and pubertal disturbances are the most common causes of morbidity, affecting 60-80% beta-thalassemia major (beta-TM) patients worldwide, due mainly to hypogonadotrophic hypogonadism (HH). We undertook a 6-year prospective study of 55 Indian beta-TM children with stunted growth and absent or arrested puberty, aged 15-18 years with pulsatile HH, to evaluate the role of low dose sex steroid priming (6-12 months) for physiological induction of puberty. Eighty percent responded favorably with increase in height, growth spurt and completed pubertal maturation [Tanner stage 4-5 (T4-T5)] and 20% moved from T2 to T3. There was biochemical improvement in maturation of hypothalamic-pituitary (H-P) axis. Those younger than 15 years with minimal iron load had the best outcome. Our data suggest that sex steroid priming is a feasible method of induction of physiological puberty in beta-TM patients with sexual infantilism and reversible apulsatile HH, especially in younger patients with minimal iron loads. PMID- 22074127 TI - Naphthalene-fused (alpha-alkoxycarbonyl)methylene-gamma-butyrolactones: antiproliferative activity and binding to bovine serum albumin and DNA. AB - A naphthalene-fused (alpha-alkoxycarbonyl)methylene-gamma-butyrolactone (methyl 2 [7-hydroxy-2-oxonaphtho[1,2-b]furan-3(2H)-yliden]acetate) has been prepared as a representative compound of a potential class of cytotoxic agents. In vitro cytotoxicity has been evaluated against HCT-15 colon and MCF-7 breast cancer cells and IC(50) was 64-66 MUM, causing morphological changes in cells, such as loss of adhesion, rounding, cell shrinkage, and detachment from the substratum. The binding constant K of the complex between the naphthyl lactone with bovine serum albumin (8 * 10(3) M(-1)) suggests a minor change in protein folding. The K of the binding with DNA (1.06 * 10(4) M(-1)) suggests nonspecific electrostatic interactions with DNA and this was confirmed by melting point data (Tm<0.6 degrees C). Therefore, naphthalene-fused (alpha-alkoxycarbonyl)methylene-gamma butyrolactone should not be able to intercalate with DNA but its interaction should occur at the level of DNA surface. PMID- 22074128 TI - Absence of association between transforming growth factor B1 polymorphisms and gastric cancer: a meta-analysis. AB - Transforming growth factor-beta1 (TGF-beta1) is a ubiquitous and essential cytokine that plays a dual role in the development of cancer: tumor suppressor in the early stage of carcinogenesis and tumor promoter in the later stage of carcinogenesis. To date, several studies have focused on the association between the TGFB1 polymorphisms and risk of gastric cancer. Conflicting results, however, have been reported. We conducted a meta-analysis to analyze more precisely the effects of the TGFB1 C-509T, T869C, and G915C polymorphisms on the risk of gastric cancer. No significant association between the TGFB1 C-509T, T869C, and G915C polymorphisms and risk of gastric cancer was observed in overall analyses and subgroup analyses according to ethnicity. PMID- 22074129 TI - Interaction of glycyrrhizin and glycyrrhetinic acid with DNA. AB - Glycyrrhizin (GL), a molecule of glycyrrhetinic acid (GA), is an aqueous extract from licorice root. These compounds are well known for their anti-inflammatory, hepatocarcinogenesis, antiviral, and interferon-inducing activities. This study is the first attempt to investigate the binding of GL and GA with DNA. The effect of ligand complexation on DNA aggregation and condensation was investigated in aqueous solution at physiological conditions, using constant DNA concentration (6.25 mM) and various ligands/polynucleotide (phosphate) ratios of 1/240, 1/120, 1/80, 1/40, 1/20, 1/10, 1/5, 1/2, and 1/1. Fourier transform infrared and ultraviolet (UV)-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of ligand-DNA complexes in aqueous solution. Spectroscopic evidence showed that GL and GA bind DNA via major and minor grooves as well as the backbone phosphate group with overall binding constants of K(GL-DNA)=5.7*10(3) M(-1), K(GA-DNA)=5.1*10(3) M(-1). The affinity of ligand-DNA binding is in the order of GL>GA. DNA remained in the B family structure, whereas biopolymer aggregation occurred at high triterpenoid concentrations. PMID- 22074131 TI - Principal component analysis and analysis of variance on the effects of Entellan New on the Raman spectra of fibers. AB - During the forensic examination of textile fibers, fibers are usually mounted on glass slides for visual inspection and identification under the microscope. One method that has the capability to accurately identify single textile fibers without subsequent demounting is Raman microspectroscopy. The effect of the mountant Entellan New on the Raman spectra of fibers was investigated to determine if it is suitable for fiber analysis. Raman spectra of synthetic fibers mounted in three different ways were collected and subjected to multivariate analysis. Principal component analysis score plots revealed that while spectra from different fiber classes formed distinct groups, fibers of the same class formed a single group regardless of the mounting method. The spectra of bare fibers and those mounted in Entellan New were found to be statistically indistinguishable by analysis of variance calculations. These results demonstrate that fibers mounted in Entellan New may be identified directly by Raman microspectroscopy without further sample preparation. PMID- 22074130 TI - An antisense transcript in the human cytomegalovirus UL87 gene region. AB - BACKGROUND: Rapid advances in research on antisense transcripts are gradually changing our comprehension of genomic and gene expression aspects of the Herpesviridae. One such herpesvirus is the human cytomegalovirus (HCMV). Although transcription of the HCMV UL87 gene has not been specifically investigated, cDNA clones of UL87 antisense transcripts were found in HCMV cDNA libraries previously. In this study, the transcription of the UL87 antisense strand was investigated in three clinically isolated HCMV strains. RESULTS: First, an 800 nucleotides transcript having an antisense orientation to the UL87 gene was found in a late HCMV cDNA library. Then, the UL87 antisense transcript was confirmed by Rapid amplification of cDNA ends (RACE) and Northern blot in three HCMV clinical strains. Two ORFs were predicted in the antisense transcript. The putative protein of ORF 1 showed a high degree of conservation among HCMV and other CMV strains. CONCLUSION: An 800nt antisense transcript in the UL87 gene region exists in HCMV clinical strains. PMID- 22074132 TI - Locating the source of hyperglycemia: liver versus muscle. AB - BACKGROUND: Glucose homeostasis relies on insulin to suppress hepatic glucose production and to stimulate glucose uptake by peripheral tissues (primarily skeletal muscle) during and after a meal or glucose load. Glucose metabolism impairments in the liver and/or muscle attenuate these insulin actions, causing hyperglycemia. Thus, identifying the loci of the impairments can improve the understanding of hyperglycemia and enable organ-targeted interventions. METHODS: Studies were performed to identify such loci using modified oral glucose tolerance test (OGTT) techniques in individuals with type 2 diabetes (T2D) and overweight/obese individuals. RESULTS: Individuals with severe T2D were found to have significantly impaired glucose metabolism in both the liver and muscle. In contrast, impairments in glucose metabolism in individuals with non-severe T2D were predominantly localized in the liver or muscle, but not both. Similarly, milder impairments in overweight or obese individuals were clearly localized in either the liver or muscle, but not both. All these impairments are quantifiable. CONCLUSION: Impairments in glucose metabolism in the liver and muscle can be differentiated and quantified in a clinical setting. PMID- 22074133 TI - Regulation and function of uncoordinated-51 like kinase proteins. AB - SIGNIFICANCE: The Atg1/ULK1 (uncoordinated-51 like kinase 1) protein complex plays an essential role regulating autophagy in mammalian cells. As autophagy is implicated in normal cellular homeostasis and multiple diseases, better mechanistic insight drives development of novel therapeutic approaches. RECENT ADVANCES: Multiple independent laboratories have contributed important new insights into the ULK-signalling pathway. ULK1/2 function is regulated by mTOR complex 1 and AMPK through a network of phosphorylation events. ULK signalling controls autophagosome formation in conjunction with other key regulatory factors such as Beclin1 and Atg9. CRITICAL ISSUES: From recent work, we have gained a better understanding of ULK proteins and their functional roles but details still need to be resolved. A combination of approaches has been used to better elucidate the sub-classes of autophagy that are differentially dependent upon ULK family members. Roles of ULK members in autophagy-independent trafficking and signalling pathways have also been better defined, highlighting the diversity of functions coordinated by this protein family. FUTURE DIRECTIONS: As mechanisms and in vivo functions become clarified for the different ULK members, more robust strategies for targeting these essential autophagy kinases can be developed. PMID- 22074134 TI - Development of autonomous microrobotics in endoscopy. AB - With experience and training the colonoscope can be a very effective tool in the screening and diagnosis of colorectal cancer. However, the colonoscope most commonly used today has changed very little in the last three decades. It is not without its problems, including a risk of perforation and significant patient discomfort, especially associated with loop formation. Furthermore, loop formation may prevent a complete colonoscopy from being performed in certain patients. In order to avoid looping formation of the colonoscopy and develop a better colonoscope it is necessary to understand the generic principle that results in the looping phenomenon. Loop formation is caused by three factors including the natural characteristic of the colon, the flexible nature of the insertion tube and the impact of frictional force on deformation of intestinal walls and mesenteries. We scientifically analyse loop formation by Kirchhoff's slender rod model, and present a review of the state-of-the-art of technologies that are being promoted as a way to address the problems of the colonoscope. PMID- 22074135 TI - A prototype of an anchoring and extending intestinal micro-robot and an in vitro experiment. AB - In order to minimize the invasiveness of intestinal disease diagnosis and surgery, we propose an anchoring and extending micro-robot. The gait of the micro robot was designed according to the biomechanical features of the intestinal tract. The locomotion condition showed that the anchoring capability and extending ability should be balanced to enhance locomotion efficiency. The mechanical and control system was designed and fabricated under the requirements of the locomotive model. The assembled micro-robot was 90 mm in length and 13 mm in diameter. The micro-robot prototype was tested in in vitro experiments; its locomotion efficiency was approximately 100% in an ideal environment, but around 50% in a pig's small bowel (20 mm in diameter). The in vitro experiment results demonstrated that the gait is feasible for locomotion in the small bowel although the diameter of the small bowel is a limiting factor. PMID- 22074139 TI - Questions and answers on feline hyperthyroidism and canine influenza. PMID- 22074136 TI - Periodical gait asymmetry assessment using real-time wireless gyroscopes gait monitoring system. AB - A real-time gait monitoring system that incorporates an immediate and periodical assessment of gait asymmetry is described. This system was designed for gait analysis and rehabilitation of patients with pathologic gait. It employs wireless gyroscopes to measure the angular rate of the thigh and shank in real time. Cross correlation of the lower extremity (Cc(norm)), and normalized Symmetry Index (SI(norm)) are implemented as new approaches to periodically determine the gait asymmetry in each gait cycle. Cc(norm) evaluates the signal patterns measured by wireless gyroscopes in each gait cycle. SI(norm) determines the movement differences between the left and right limb. An experimental study was conducted to examine the viability of these methods. Artificial asymmetrical gait was simulated by placing a load on one side of the limbs. Results showed that there were significant differences between the normal gait and asymmetrical gait (p < 0.01). They also indicated that the system worked well in periodically assessing the gait asymmetry. PMID- 22074140 TI - Reviews on animal diseases recently published in other journals. PMID- 22074142 TI - Identification of benzoxazin-3-one derivatives as novel, potent, and selective nonsteroidal mineralocorticoid receptor antagonists. AB - Mineralocorticoid receptor (MR) blockade has come into focus as a promising approach for the treatment of cardiovascular diseases such as hypertension and congestive heart failure. In order to identify a novel class of nonsteroidal MR antagonists that exhibit significant potency and good selectivity over other steroidal hormone receptors, we designed a novel series of benzoxazin-3-one derivatives and synthesized them from 6-(7H-[1,2,4]triazolo[3,4 b][1,3,4]thiadiazin-6-yl)-2H-1,4-benzoxazin-3(4H)-one (1a), high-throughput screening (HTS) hit compound. Our design was based on a crystal structure of an MR/compound complex and a docking model. In the course of lead generation from 1a, a 1,2-diaryl framework was characterized as a key structure with high binding affinity. On the basis of scaffold hopping and optimization studies, benzoxazin-3 one derivatives possessing 1-phenyl-3-trifluoromethylpyrazol-5-yl moiety at the 6 position were identified as a novel series of potent and selective MR antagonists. Among these compounds, 6-[1-(4-fluoro-2-methylphenyl)-3 (trifluoromethyl)-1H-pyrazol-5-yl]-2H-1,4-benzoxazin-3(4H)-one (14n) showed highly potent activity and good selectivity and also exhibited a significant antihypertensive effect in deoxycorticosterone acetate-salt hypertensive rats. On the basis of these results, compound 14n was progressed for further pharmacological evaluation. PMID- 22074143 TI - Commentary on "communication strategies to improve HIV treatment adherence" by Rochon et al. (2011). PMID- 22074144 TI - Obesity and type 2 diabetes: which patients are at risk? AB - An estimated 72.5 million American adults are obese, and the growing US obesity epidemic is responsible for substantial increase in morbidity and mortality, as well as increased health care costs. Obesity results from a combination of personal and societal factors, but is often viewed as a character flaw rather than a medical condition. This leads to stigma and discrimination towards obese individuals and decreases the likelihood of effective intervention. Conditions related to obesity are increasingly common, such as metabolic syndrome, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), all of which indicate high risk for type 2 diabetes (T2DM). This paper reviews the progression from obesity to diabetes, identifying physiological changes that occur along this path as well as opportunities for patient identification and disease prevention. Patients with prediabetes (defined as having IFG, IGT or both) and/or metabolic syndrome require interventions designed to preserve insulin sensitivity and beta cell function, both of which start to deteriorate prior to T2DM diagnosis. Lifestyle modification, including both healthy eating choices and increased physical activity, is essential for weight management and diabetes prevention. Although sustained weight loss is often considered by patients and physicians as being impossible to achieve, effective interventions do exist. Specifically, the Diabetes Prevention Program (DPP) and programs modelled along its parameters have shown repeated successes, even with long-term maintenance. Recent setbacks in the development of medications for weight loss further stress the importance of lifestyle management. By viewing obesity as a metabolic disorder rather than a personal weakness, we can work with patients to address this increasingly prevalent condition and improve long-term health outcomes. PMID- 22074146 TI - Editorial: Citation analysis--focus on leading Australian nurse authors. PMID- 22074147 TI - Reducing surgical nurses' aseptic practice-related stress. AB - AIMS AND OBJECTIVES: This paper aims to explore aseptic practice-related stress in surgery. The objectives are to define stress-related factors and the means to reduce the stress. BACKGROUND: Occupational stress is related to personal characteristics: job satisfaction and physiological and psychological well-being. The stress symptoms are often classified as part of a negative mood. Nurses have expressed stress when deadening their conscience to external demands with co workers or internal working role-related demands. Surgery nurses expect fair division of work and compliance with rules. The hospital management, technology and the medical profession, instead of the needs of the patient, are recognised as a danger in the development of surgery nurses' role. DESIGN: A qualitative stimulated recall interview was performed in the surgery of the university hospital. METHODS: Thirty-one operations were videotaped, and 31 nurses interviewed during videotape stimulation. The 1306 text pages were transcripted and analysed by a qualitative membership categorisation device analysis. RESULTS: The analysis revealed aseptic practice-related stress which constructed a sixteen level category. The membership categorisation identified connections between qualitatively attributed personnel and seven stress factors: working experience; time; equipment; person; patient; working morals and power. Final analysis revealed nurses reducing aseptic practice-related stress by safe, peaceful, competent and relative means. CONCLUSIONS: The aseptic practice-related stress varied from positive motivating feelings to exhaustion. The stress was experienced by medical and nursing co-workers and reduced by means which varied according to expertise and co-workers. RELEVANCE TO CLINICAL PRACTICE: This study showed needs for both the shared multiprofessional documentation of aseptic practice and better adherence to recommendations. Constructive means are useful when solving conflicts and replacing person-related aseptic practice with evidence-based. They may support nurses' professional growth, reduce their stress and increase the surgical patient's safety. PMID- 22074148 TI - Identifying service needs from the users and service providers' perspective: a focus group study of Chinese elders, health and social care professionals. AB - AIM: This is a preliminary study to identify older people service needs in Hong Kong from the users' and service providers' perspective. BACKGROUND: As the Hong Kong population is ageing rapidly, it is important to identify the needs for care of older people. Although a wide variety of medical and social services have been provided to meet the needs of older people, there has been little evaluation from the users' or service providers' perspective regarding what the needs are and how well current service provisions match their needs. In recent years the importance of patient-centred care has been emphasised, where patient's expectation of care has been given a central role in guiding and improving the provision of health. However few studies have been carried out with respect to services for older people. DESIGN: To identify the service needs, a focus group study was conducted. Both service providers and older people were interviewed. This preliminary study used a qualitative research method to identify older people's service needs, generating rich information which could be used to inform older people care service development. METHOD: Data were collected by conducting eight focus group discussions. The focus group interviews were audio-taped. Interviews were then transcribed and themes were identified. RESULTS: The study identified several areas for improvement in services for older people, covering adequacy, accessibility and affordability of medical services, coordination of health and social care, quality of long-term care, negative perceptions and training needs. Some themes such as service adequacy and negative staff attitudes occurred in both older people and health professional focus groups. The themes of fast access, continuity of care and smooth transition, affordability, provision of information of available health and social services appear to be universal as these have also been identified in similar studies in other countries. CONCLUSION: In addition to other objective outcomes, such as duration of stay in hospital or re-admission rates after hospital discharges, changes in service provisions towards improvement should be evaluated from the users as well as professional care providers' perspectives. RELEVANCE TO CLINICAL PRACTICE: Areas of improvement in service delivery include timely access, continuity, affordability, better coordination of health and social care, quality of care particularly in the long-term residential care setting and healthcare professionals' communication and caring skills and attitude. PMID- 22074149 TI - Low bone mineral density in a cohort of normal, overweight and obese Chilean adolescents. PMID- 22074150 TI - Commentary on Su SF, Boore J, Jenkins M, Liu PE & Yang MJ (2009) Nurses' perception of environmental pressure in relation to their occupational stress. Journal of Clinical Nursing 18, 3172-3180. PMID- 22074151 TI - Commentary on McNamara M & Fealy G (2010) Editorial: Lead us not again. Journal of Clinical Nursing 19, 3257-3259. PMID- 22074152 TI - Response to Ingleton C & Green E (2010) Commentary on Metcalfe A, Pumphrey R & Clifford C (2009) Hospice nurses' and genetics: implications for end-of-life care. Journal of Clinical Nursing 19, 192-207. PMID- 22074153 TI - Response to Ski CF & Thompson DR (2011) Commentary on Yohannes AM, Doherty P, Bundy C & Yalfani A (2010) The long-term benefits of cardiac rehabilitation on depression, anxiety, physical activity and quality of life. Journal of Clinical Nursing 19, 2806-2813. PMID- 22074154 TI - Metal-specific interactions of H2 adsorbed within isostructural metal-organic frameworks. AB - Diffuse reflectance infrared (IR) spectroscopy performed over a wide temperature range (35-298 K) is used to study the dynamics of H(2) adsorbed within the isostructural metal-organic frameworks M(2)L (M = Mg, Mn, Co, Ni and Zn; L = 2,5 dioxidobenzene-1,4-dicarboxylate) referred to as MOF-74 and CPO-27. Spectra collected at H(2) concentrations ranging from 0.1 to 3.0 H(2) per metal cation reveal that strongly red-shifted vibrational modes arise from isolated H(2) bound to the available metal coordination site. The red shift of the bands associated with this site correlate with reported isosteric enthalpies of adsorption (at small surface coverage), which in turn depend on the identity of M. In contrast, the bands assigned to H(2) adsorbed at positions >3 A from the metal site exhibit only minor differences among the five materials. Our results are consistent with previous models based on neutron diffraction data and independent IR studies, but they do not support a recently proposed adsorption mechanism that invokes strong H(2)...H(2) interactions (Nijem et al. J. Am. Chem. Soc.2010, 132, 14834-14848). Room temperature IR spectra comparable to those on which the recently proposed adsorption mechanism was based were only reproduced after contaminating the adsorbent with ambient air. Our interpretation that the uncontaminated spectral features result from stepwise adsorption at discrete framework sites is reinforced by systematic red shifts of adsorbed H(2) isotopologues and consistencies among overtone bands that are well-described by the Buckingham model of molecular interactions in vibrational spectroscopy. PMID- 22074155 TI - Parents reported oral sensory sensitivity processing and food preference in ADHD. AB - Oral sensory processing in children with attention deficit hyperactivity disorder (ADHD) is an area with limited research. Oppositional defiant disorder (ODD) and separation anxiety disorder (SAD) symptoms usually co-occur with ADHD. This study investigates the association of oral sensory processing problems with ODD and SAD symptoms in children with ADHD. The parents of 189 children with ADHD completed Oral Over- and Underresponsivity Behaviors Inventory reporting oral overresponsivity (OR) and underresponsivity (UR) of their children. Only ODD score predicted OR scale score. None of ADHD severity, anxiety score, age and gender predicted OR score. UR scale score was only predicted by SAD and inattention scores. ODD score and hyperactivity/impulsivity score did not predict UR score. The ODD behaviour in children with ADHD needs to be evaluated and managed more extensively and it should include oral sensory occupational therapy. Future studies should extend this research to children with ADHD and obesity and food reward system. PMID- 22074156 TI - Predictors of failure following restrictive annuloplasty for chronic ischemic mitral regurgitation. AB - AIM OF THE STUDY: We sought to determine the results of restrictive annuloplasty for chronic ischemic mitral regurgitation. METHODS: Hospital outcome and serial clinical and echocardiographic (preoperative, discharge, 3 months, 12 months, 24 months) follow-up assessments were analyzed in 87 consecutive patients with chronic ischemic mitral regurgitation having coronary artery bypass grafting. Persistent/recurrent mitral regurgitation was defined by grade >=2 at discharge/during follow-up. RESULTS: Hospital mortality was 5.7% and persistence of regurgitation was present in 8.4%. Mean follow-up was 24.4 +/- 1.7 months and recurrent mitral regurgitation was observed in 32.4% patients. In multivariate analysis only anterior leaflet angle remained an independent predictive factor for regurgitation recurrence with cutoff 27 degrees (sensitivity of 67% and specificity of 76%, p = 0.04). CONCLUSION: There is high occurrence of early and delayed restrictive annuloplasty failure, particularly in patients with increased anterior leaflet tethering. PMID- 22074158 TI - Sense of coherence and suicidality in suicide attempters: a prospective study. AB - The usefulness of the Sense of Coherence (SOC) scale in the nursing setting is well-established, and an association between SOC and suicidality has been suggested. The aim was to test whether low SOC at index attempt is an independent predictor of suicidality at 2-month follow-up and of risk for repeat attempt. The study, which had a prospective cross-sectional design, included patients admitted to hospital after a suicide attempt. They were interviewed by means of Structured Clinical Interview for DSM-IV. Participants (n=155) completed the SOC scale and the Comprehensive Psychopathological Self-rating Scale for Affective Syndromes. Suicidality was rated with the Suicide Assessment Scale. Instruments were employed again at follow-up. Non-fatal/fatal repetition within 3 years was determined by review of hospital records. Low SOC at baseline predicted high suicidality at follow-up. The association remained after adjustment for major depression and affective symptom burden. Repeat attempts were made by 54 persons. Low baseline SOC was associated with repeat attempt, but the association did not remain after adjustment for major depression and symptom burden. Low SOC ratings could be a marker of risk for high suicidality in the aftermath of a suicide attempt. The SOC scale could be incorporated in nursing assessments of suicide attempters. PMID- 22074157 TI - Pentoxifylline sensitizes human cervical tumor cells to cisplatin-induced apoptosis by suppressing NF-kappa B and decreased cell senescence. AB - BACKGROUND: Worldwide, cervical cancer is the second most common causes of cancer in women and represents an important mortality rate. Cisplatin (CIS) is a very important antitumoral agent and can lead tumor cells toward two important cellular states: apoptosis and senescence. In some types of cancers pentoxifylline (PTX) sensitizes these cells to the toxic action of chemotherapeutics drugs such as adriamycin, inducing apoptosis. In the present work, we studied in vitro whether PTX alone or in combination with CIS induces apoptosis and/or senescence in cervix cancer HeLa and SiHa cell lines infected with HPV types 16 and 18, respectively, as well as in immortalized keratinocytyes HaCaT cells. METHODS: HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non tumorigenic immortalized HaCaT cells (control) were treated with PTX, CIS or both. The cellular toxicity and survival fraction of PTX and CIS were determinate by WST-1 and clonogenic assays respectively. Apoptosis, caspase activation and phosphorylation of ERK1/2, p38, p65 (NF-kappaB), Bcl-2 and Bcl-XL anti-apoptotic proteins were determinated by flow cytometry. Senescence by microscopy. Phosphorylation of IkappaBalpha and IkappaB total were measured by ELISA. Pro apoptotic, anti-apoptotic and senescence genes, as well as HPV-E6/7 mRNA expression, were detected by RT-PCR. RESULTS: Our results show that after 24 hours of incubation PTX per se is toxic for cancer cells affecting cell viability and inducing apoptosis. The toxicity in HaCaT cells was minimal. CIS induces apoptosis in HeLa and SiHa cells and its effect was significantly increases when the cells were treated with PTX + CIS. In all studies there was a direct correlation with levels of caspases (-3, -6, -7, -9 and -8) activity and apoptosis. CIS induces important levels of senescence and phosphorylation of ERK1/2, p38, p65/RELA, and IkappaBalpha, and decreased the expression of anti apoptotic protein Bcl-XL. Surprisingly these levels were significantly reduced by PTX in tumor cells, and at the same time, increases the expression of pro apoptotic genes. CONCLUSION: PTX sensitizes cervical cancer cells to CIS-induced apoptosis and decreases the CIS-induced senescence in these cells via inhibition of NF-kappaB signaling pathway; diminishes expression of antiapoptotic proteins and the activation of caspases. PMID- 22074159 TI - Improved two-dimensional reversed phase-reversed phase LC-MS/MS approach for identification of peptide-protein interactions. AB - Quantitative mass spectrometry (MS) in combination with affinity purification approaches allows for an unbiased study of protein-protein and peptide-protein interactions. In shotgun approaches that are based on proteolytic digestion of complex protein mixtures followed by two-dimensional liquid-phase chromatography, the separation effort prior to MS analysis is focused on tryptic peptides. Here we developed an improved offline 2-D liquid chromatography-MS/MS approach for the identification and quantification of binding proteins utilizing reversed-phase capillary columns with acidic acetonitrile-containing eluents in both chromatographic dimensions. A specific fractionation scheme was applied in order to obtain samples with evenly distributed peptides and to fully utilize the separation space in the second dimension nanoLC-MS/MS. We report peptide-protein interaction studies to identify phosphorylation-dependent binding partners of the T cell adapter protein ADAP. The results of the SILAC-based pull-down experiments show this approach is well suited for distinguishing phosphorylation-specific interactions from unspecific binding events. The data provide further evidence that phosphorylated Tyr 595 of ADAP may serve as a direct binding site for the SH2 domains of the T cell proteins SLP76 and NCK. From a technical point of view we provide a detailed protocol for an offline 2-D RP-RP LC-MS/MS method that offers a robust and time-saving alternative for quantitative interactome analysis. PMID- 22074160 TI - Fertility and economic status - some recent findings on differentials in Sweden. AB - Abstract The relationship between economic status and family size has generally been found to be negative; the lower the income the higher the fertility. In some cases this inverse relationship breaks down at the top end of the income scale; in other words, people with very high incomes have larger families than those with high incomes. In a few rather special cases positive relationships have been found(1). PMID- 22074161 TI - Some observations on the economic framework for fertility analysis. AB - Abstract The economic framework for fertility analysis, first expounded in detail by Gary S. Becker(1), has attracted considerable attention among demographers. While some writers have enthusiastically endorsed the model, others have rejected it outright(3). A few attempts have also recently been made by some writers to modify or refine some of the concepts employed, and/or to change the modes of treatment of some of the factors in the original model. Unfortunately, several major objections levelled against the model still remain. It also remains to be examined whether the criticisms can be met without violating the principles and strategies espoused by economists. I believe (1) that most of the objections advanced against the model can be met by suitably modifying it, and (2) that the required modifications can be effected by employing strategies and conceptual schemes similar to those used in the demand analysis of consumer behaviour. The objective of this paper is to expound this belief. There is a strong possibility that after modification a healthy new theory will emerge which may prove useful in guiding research, as well as help to bring together different empirical findings in the literature, or to serve as a 'binder' for the theoretical speculations advanced by many research workers. PMID- 22074162 TI - The price of children and socio-economic theories of fertility. AB - Abstract Demographers have for some time suggested that the cost of children has an important bearing on couples' fertility decisions. Dublin and Lotka, for example, voiced the opinion that 'it is undoubtedly the anticipation of greatly increased expenditures, the sudden demands made on the family exchequer when a child is born and for some time after, that causes people of limited income to restrict the size of their families'. Banks, Myrdal, and Day and Day have echoed this same theme. PMID- 22074163 TI - Projected consumption patterns for a stationary population. AB - Abstract Recently economists have demonstrated a renewed interest in the population problems of a mature society. This revival of interest has been sparked by the general recognition of the relationship between population growth and environmental problems and has led to general acceptance of the proposition that ' ... a zero rate of population growth is the only equilibrium rate that can be sustained'.(1) Consequently the literature produced during the discipline's last period of similar concern, a period running from the late 1920's through the 1940's, needs re-examination. At that time economists were primarily occupied with the implications of a declining rate of population growth and most anticipated the arrival of a stationary population within the foreseeable future. For most of the economists of this earlier period the onset of a stationary or declining population was fraught with dangers for mature capitalism. PMID- 22074164 TI - Institutionalized motivation for fertility limitation in China. AB - Abstract After initial misgivings based on orthodox Marxist ideology regarding population control, the People's Republic of China officially came out in favour of population limitation. The government denies the dire Malthusian prophecy that population will outstrip China's supply of food and natural resources. Instead it supports population limitation to ease the costs of economic growth, which under Chinese conditions requires a strong labour force and a concentration of capital in productive enterprises rather than a high rate of consumption. By applying the experience of the developed nations, China has reduced pre-industrial levels of mortality and morbidity. This has decreased the expense to society of a non productive populace which dies before it repays the costs of its upbringing and training. As a result, China undoubtedly has a high rate of population growth. Lower fertility will lessen the proportion of children to adult workers and will release females for employment; for these reasons the government advocates fertility control. Observers lack data from the two national censuses (1953-54 and 1964) and registration system to assess China's success in fertility reduction. Instead the patterns of social mobility and social control which shape reproductive motivation must be evaluated. In so doing I address myself to one main question: how has China's approach to economic development in the past five years affected the motivation of her youth to reduce fertility? PMID- 22074165 TI - Marriage at an earlier than ideal age in six Latin American capital cities. AB - Abstract The study of nuptiality has taken on urgency, for demographers as well as for sociologists, with the increased world concern over sustained high fertility and the evident contribution of early marriage to that high fertility. Moreover, along with despair over the efficacy of conventional family planning programmes has come an expectation that more basic institutional changes, such as changes in marriage patterns, will be necessary in order finally to achieve a tolerably low world population growth rate. Yet our understanding of the determinants of such primary nuptiality dimensions as age at first marriage is very imperfect and unlikely to give much guidance in policy formation. PMID- 22074166 TI - Number and mean age of acceptors and users as related to programme duration. AB - Abstract A decline in annual acceptances in a contraceptive programme is open to multiple interpretation. The decline may reflect an adverse change of attitudes and therefore a lowered disposition to accept the method among couples of the population generally. Alternatively, if the population has an irregular age distribution, the decline may mean only that the numbers of couples of prime contraceptive age have temporarily dropped. Thirdly, if the rate of previous acceptance has been high, the main cause of a slackening in new acceptances may simply be that previous acceptances have partially depleted the pool of eligible couples. Fewer eligible couples are left than previously as a consequence of past acceptance, removing couples interested in contraception faster than the family building process can create new ones. PMID- 22074167 TI - Comment on 'expectancy of life at birth in 36 nationalities of the Soviet Union: 1958-60'. AB - Abstract In D. Peter Mazur's recent article, 'Expectancy of Life at Birth in 36 Nationalities of the Soviet Union: 1958-1960', crude rates of death and expectancies of life for nationalities are derived from a scant base of data that includes crude rates of natural increase for administrative units and various ratios of composition of the populations of both administrative units and nationalities. Students of Soviet demography genuinely appreciate Mazur's attempt to derive rich results from meagre data. Of course, to do this strong assumptions are required and Mazur warns that 'the quantitative results ... are valid only to the extent that the underlying methodology is theoretically sound'. One way to test the quantitative results is to examine how well the crude death rates for the nationalities calculated by Mazur reproduce the crude death rates for administrative units with which Mazur started. Mazur feels that the estimated death rates for nationalities closely agree with the death rates for administrative areas. The present author is sceptical. Application of the method described below does not show close correspondence, and this matter, which is crucial in the evaluation of Mazur's results, seems problematical. PMID- 22074168 TI - Crude death rates in the U.S.S.R.: Comment on Grandstaff's remarks. AB - Abstract My appraisal of death rates in the U.S.S.R. goes beyond the question whether a simple correlation really measures what the critic purports to measure. Normally, the crude death rates depend upon the age structure and the force of mortality. If one persists in assuming that a reasonably high correlation between the official death rates and their independent estimates should be the main criterion of validity, the best technique will be to relate the proportion of persons aged 60 and over to the official death rates recorded for some 109 observations. The force of mortality would be approximately reflected by a given proportion of survivors to the first or second year of age. But in the 1959 Soviet Census the latter data had been concealed within the 0 to 9 age group, possibly for no other reason than to prevent the curious few from tinkering with infant mortality. PMID- 22074171 TI - Folic acid modified gelatine coated quantum dots as potential reagents for in vitro cancer diagnostics. AB - BACKGROUND: Gelatine coating was previously shown to effectively reduce the cytotoxicity of CdTe Quantum Dots (QDs) which was a first step towards utilising them for biomedical applications. To be useful they also need to be target specific which can be achieved by conjugating them with Folic Acid (FA). RESULTS: The modification of QDs with FA via an original "one-pot" synthetic route was proved successful by a range of characterisation techniques including UV-visible absorption spectroscopy, Photoluminescence (PL) emission spectroscopy, fluorescence life-time measurements, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The resulting nanocomposites were tested in Caco 2 cell cultures which over-express FA receptors. The presence of FA on the surface of QDs significantly improved the uptake by targeted cells. CONCLUSIONS: The modification with folic acid enabled to achieve a significant cellular uptake and cytotoxicity towards a selected cancer cell lines (Caco-2) of gelatine-coated TGA-CdTe quantum dots, which demonstrated good potential for in vitro cancer diagnostics. PMID- 22074173 TI - 'Irresponsible and a disservice': the integrity of social psychology turns on the free will dilemma. AB - Over the last few years, a number of works have been published asserting both the putative prosocial benefits of belief in free will and the possible dangers of disclosing doubts about the existence of free will. Although concerns have been raised over the disservice of keeping such doubts from the public, this does not highlight the full danger that is presented by social psychology's newly found interest in the 'hard problem' of human free will. Almost all of the work on free will published to date by social psychologists appears methodologically flawed, misrepresents the state of academic knowledge, and risks linking social psychology with the irrational. PMID- 22074172 TI - The acid-tolerant L-arabinose isomerase from the mesophilic Shewanella sp. ANA-3 is highly active at low temperatures. AB - BACKGROUND: L-arabinose isomerases catalyse the isomerization of L-arabinose into L-ribulose at insight biological systems. At industrial scale of this enzyme is used for the bioconversion of D-galactose into D-tagatose which has many applications in pharmaceutical and agro-food industries. The isomerization reaction is thermodynamically equilibrated, and therefore the bioconversion rates is shifted towards tagatose when the temperature is increased. Moreover, to prevent secondary reactions it will be of interest to operate at low pH. The profitability of this D-tagatose production process is mainly related to the use of lactose as cheaper raw material. In many dairy products it will be interesting to produce D-tagatose during storage. This requires an efficient L-arabinose isomerase acting at low temperature and pH values. RESULTS: The gene encoding the L-arabinose isomerase from Shewanella sp. ANA-3 was cloned and overexpressed in Escherichia coli. The purified protein has a tetrameric arrangement composed by four identical 55 kDa subunits. The biochemical characterization of this enzyme showed that it was distinguishable by its maximal activity at low temperatures comprised between 15-35 degrees C. Interestingly, this biocatalyst preserves more than 85% of its activity in a broad range of temperatures from 4.0 to 45 degrees C. Shewanella sp. ANA-3 L-arabinose isomerase was also optimally active at pH 5.5 6.5 and maintained over 80% of its activity at large pH values from 4.0 to 8.5. Furthermore, this enzyme exhibited a weak requirement for metallic ions for its activity evaluated at 0.6 mM Mn2+. Stability studies showed that this protein is highly stable mainly at low temperature and pH values. Remarkably, T268K mutation clearly enhances the enzyme stability at low pH values. Use of this L-arabinose isomerase for D-tagatose production allows the achievement of attractive bioconversion rates of 16% at 4 degrees C and 34% at 35 degrees C. CONCLUSIONS: Here we reported the purification and the biochemical characterization of the novel Shewanella sp. ANA-3 L-arabinose isomerase. Determination of the biochemical properties demonstrated that this enzyme was highly active at low temperatures. The generated T268K mutant displays an increase of the enzyme stability essentially at low pH. These features seem to be very attractive for the bioconversion of D-galactose into D-tagatose at low temperature which is very interesting from industrial point of view. PMID- 22074174 TI - Reconciling sectoral abatement strategies with global climate targets: the case of the Chinese passenger vehicle fleet. AB - The IPCC Forth Assessment Report postulates that global warming can be limited to 2 degrees C by deploying technologies that are currently available or expected to be commercialized in the coming decades. However, neither specific technological pathways nor internationally binding reduction targets for different sectors or countries have been established yet. Using the passenger car stock in China as example we compute direct CO(2) emissions until 2050 depending on population, car utilization, and fuel efficiency and compare them to benchmarks derived by assuming even contribution of all sectors and a unitary global per capita emission quota. Compared to present car utilization in industrialized countries, massive deployment of prototypes of fuel efficient cars could reduce emissions by about 45%, and moderately lower car use could contribute with another 33%. Still, emissions remain about five times higher than the benchmark for the 2 degrees C global warming target. Therefore an extended analysis, including in particular low-carbon fuels and the impact of urban and transport planning on annual distance traveled and car ownership, should be considered. A cross-sectoral comparison could reveal whether other sectors could bear an overproportional reduction quota instead. The proposed model offers direct interfaces to material industries, fuel production, and scrap vehicle supply. PMID- 22074176 TI - Evaluation of biosafety and intracellular uptake of Cremophor EL free paclitaxel elastic liposomal formulation. AB - The present study examines the acute, sub-acute toxicity, and cytotoxicity of paclitaxel elastic liposomal formulation in comparison to a marketed Cremophor EL (polyoxyethylated castor oil):ethanol (1:1, v/v) based formulation. In the previous study, Cremophor EL free paclitaxel elastic liposomal formulation was developed and characterized. Cytotoxicity of formulation was evaluated by MTT assay using A549 cell lines. Percentage intracellular uptake of paclitaxel elastic liposomal and marketed formulation was determined using a fluorescence activating cell sorting assay (FACS) and fluorescence microscopy techniques. Single and repeated dose toxicity measurement showed no mortality, hematological, biochemical, or histopathological changes up to a dose of 120 mg/kg for paclitaxel elastic liposomal formulation, in comparison the marketed formulation showed toxicity at a dose of 40 mg/kg. Maximum tolerated dose (MTD) for paclitaxel elastic liposomal and marketed formulation was found to be 160 mg/kg and 40 mg/kg, respectively. Results of FACS analysis showed a 94.6 +/- 2.5% intracellular uptake of fluorescence marker acridine orange (AO) loaded in elastic liposomes; in comparison the AO solution showed only a 19.8 +/- 1.1% uptake. Paclitaxel elastic liposomal formulation seems to be a better alternative for safe and effective delivery of paclitaxel. This study proves the safety and higher intracellular uptake of paclitaxel elastic liposomal formulation. PMID- 22074178 TI - No effects of Korean pine nut triacylglycerol on satiety and energy intake. AB - BACKGROUND: Triacylglycerols (TAG) have been shown to have potential appetite suppressing effects. This study examined the effects of 3 g and 6 g Korean pine nut triacylglycerols (PinnoThin) on appetite and energy intake. METHODS: 130 g Isoenergetic yogurt containing either placebo (milk fat) or PinnoThin TAG was consumed as a breakfast, after an overnight fast, in a double blind randomized crossover design. Appetite profile ratings were determined by visual analogue scale at regular intervals for a period of 4 h after the breakfast. In phase I, 6 g PinnoThin TAG and placebo was tested in thirty-three healthy women (mean +/- SD, BMI 26.4 +/- 3.8 kg/m2; age 28 +/- 10 y) to determine the appetite suppressing effect in time. In phase II, an additional dose of 3 g PinnoThin TAG, as well as 6 g PinnoThin TAG and placebo, was tested in thirty-four women (BMI 25.8 +/- 2.9 kg/m2; age 25 +/- 9 y) to determine energy intake from an ad libitum lunch offered at 210 min after the breakfast, at which maximal differences in appetite profile ratings were present in phase I. RESULTS: Area under the curve of appetite profile ratings was not significantly different between the conditions. Energy intake was 9.5% lower after 6 g PinnoThin TAG compared with 3 g PinnoThin TAG, but there was no significant difference with the placebo. CONCLUSION: A dosage of 6 g PinnoThin TAG is not sufficient to suppress appetite and energy intake. TRIAL REGISTRATION: Clinical Trials NCT01034605. PMID- 22074177 TI - Oxygen-independent alkane formation by non-heme iron-dependent cyanobacterial aldehyde decarbonylase: investigation of kinetics and requirement for an external electron donor. AB - Cyanobacterial aldehyde decarbonylase (cAD) is, structurally, a member of the di iron carboxylate family of oxygenases. We previously reported that cAD from Prochlorococcus marinus catalyzes the unusual hydrolysis of aldehydes to produce alkanes and formate in a reaction that requires an external reducing system but does not require oxygen [Das et al. (2011) Angew. Chem. 50, 7148-7152]. Here we demonstrate that cADs from divergent cyanobacterial classes, including the enzyme from N. puntiformes that was reported to be oxygen dependent, catalyze aldehyde decarbonylation at a much faster rate under anaerobic conditions and that the oxygen in formate derives from water. The very low activity (<1 turnover/h) of cAD appears to result from inhibition by the ferredoxin reducing system used in the assay and the low solubility of the substrate. Replacing ferredoxin with the electron mediator phenazine methosulfate allowed the enzyme to function with various chemical reductants, with NADH giving the highest activity. NADH is not consumed during turnover, in accord with the proposed catalytic role for the reducing system in the reaction. With octadecanal, a burst phase of product formation, k(prod) = 3.4 +/- 0.5 min(-1), is observed, indicating that chemistry is not rate-determining under the conditions of the assay. With the more soluble substrate, heptanal, k(cat) = 0.17 +/- 0.01 min(-1) and no burst phase is observed, suggesting that a chemical step is limiting in the reaction of this substrate. PMID- 22074179 TI - Dehydratase mediated 1-propanol production in metabolically engineered Escherichia coli. AB - BACKGROUND: With the increasing consumption of fossil fuels, the question of meeting the global energy demand is of great importance in the near future. As an effective solution, production of higher alcohols from renewable sources by microorganisms has been proposed to address both energy crisis and environmental concerns. Higher alcohols contain more than two carbon atoms and have better physiochemical properties than ethanol as fuel substitutes. RESULTS: We designed a novel 1-propanol metabolic pathway by expanding the well-known 1,2-propanediol pathway with two more enzymatic steps catalyzed by a 1,2-propanediol dehydratase and an alcohol dehydrogenase. In order to engineer the pathway into E. coli, we evaluated the activities of eight different methylglyoxal synthases which play crucial roles in shunting carbon flux from glycolysis towards 1-propanol biosynthesis, as well as two secondary alcohol dehydrogenases of different origins that reduce both methylglyoxal and hydroxyacetone. It is evident from our results that the most active enzymes are the methylglyoxal synthase from Bacillus subtilis and the secondary alcohol dehydrogenase from Klebsiella pneumoniae, encoded by mgsA and budC respectively. With the expression of these two genes and the E. coli ydjG encoding methylglyoxal reductase, we achieved the production of 1,2-propanediol at 0.8 g/L in shake flask experiments. We then characterized the catalytic efficiency of three different diol dehydratases on 1,2-propanediol and identified the optimal one as the 1,2-propanediol dehydratase from Klebsiella oxytoca, encoded by the operon ppdABC. Co-expressing this enzyme with the above 1,2-propanediol pathway in wild type E. coli resulted in the production of 1 propanol at a titer of 0.25 g/L. CONCLUSIONS: We have successfully established a new pathway for 1-propanol production by shunting the carbon flux from glycolysis. To our knowledge, it is the first time that this pathway has been utilized to produce 1-propanol in E. coli. The work presented here forms a basis for further improvement in production. We speculate that dragging more carbon flux towards methylglyoxal by manipulating glycolytic pathway and eliminating competing pathways such as lactate generation can further enhance the production of 1-propanol. PMID- 22074180 TI - RETRACTED: Inhibition of LXRalpha-dependent steatosis and oxidative injury by liquiritigenin, a licorice flavonoid, as mediated with Nrf2 activation. PMID- 22074181 TI - Synthesis and properties of molecular probes for the rescue site on mutant cystic fibrosis transmembrane conductance regulator. AB - Cystic fibrosis is a genetic disease caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In vitro experiments have demonstrated that 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)phenol (VRT-532, 1) is able to partially restore the function of mutant CFTR proteins. To help elucidate the nature of the interactions between 1 and mutant CFTR, molecular probes based on the structure of 1 have been prepared. These include a photoreactive aryl azide derivative 11 and a fluorescent dansyl sulfonamide 15. Additionally, a method for hydrogen isotope exchange on 1 has been developed, which could be used for the incorporation of radioactive tritium. Using iodide efflux assays, the probe molecules have been demonstrated to modulate the activity of mutant CFTR in the same manner as 1. These probe molecules enable a number of biochemical experiments aimed at understanding how 1 rescues the function of mutant CFTR. This understanding can in turn aid in the design and development of more efficacious compounds which may serve as therapeutic agents in the treatment of cystic fibrosis. PMID- 22074182 TI - A small molecule that binds to an ATPase domain of Hsc70 promotes membrane trafficking of mutant cystic fibrosis transmembrane conductance regulator. AB - Cystic fibrosis transmembrane conductance regulator (CFTR) is a cell-surface anion channel that permeates chloride and bicarbonate ions. The most frequent mutation of CFTR that causes cystic fibrosis is the deletion of phenylalanine at position 508 (DeltaF508), which leads to defects in protein folding and cellular trafficking to the plasma membrane. The lack of the cell-surface CFTR results in a reduction in the lifespan due to chronic lung infection with progressive deterioration of lung function. Hsc70 plays a crucial role in degradation of mutant CFTR by the ubiquitin-proteasome system. To date, various Hsc70 inhibitors and transcription regulators have been tested to determine whether they correct the defective activity of mutant CFTR. However, they exhibited limited or questionable effects on restoring the chloride channel activity in cystic fibrosis cells. Herein, we show that a small molecule apoptozole (Az) has high cellular potency to promote membrane trafficking of mutant CFTR and its chloride channel activity in cystic fibrosis cells. Results from affinity chromatography and ATPase activity assay indicate that Az inhibits the ATPase activity of Hsc70 by binding to its ATPase domain. In addition, a ligand-directed protein labeling and molecular modeling studies also suggest the binding of Az to an ATPase domain, in particular, an ATP-binding pocket. It is proposed that Az suppresses ubiquitination of DeltaF508-CFTR maybe by blocking interaction of the mutant with Hsc70 and CHIP, and, as a consequence, it enhances membrane trafficking of the mutant. PMID- 22074183 TI - Adsorption of poly(vinyl formamide-co-vinyl amine) (PVFA-co-PVAm) polymers on zinc, zinc oxide, iron, and iron oxide surfaces. AB - The adsorption of poly(vinyl formamide) (PVFA) and the statistic copolymers poly(vinyl formamide-co-vinyl amine) (PVFA-co-PVAm) onto zinc and iron metal particles as well as their oxides was investigated. The adsorbates were characterized by means of XPS, DRIFT spectroscopy, wet chemical analysis, and solvatochromic probes. Dicyano-bis-(1,10-phenanthroline)-iron(II) (1), 3-(4-amino 3-methylphenyl)-7-phenyl-benzo-[1,2-b:4,5-b']difuran-2,6-dione (2), and 4-tert butyl-2-(dicyano-methylene)-5-[4-(diethylamino)-benzylidene]-Delta(3)-thiazoline (3) as solvatochromic probes were coadsorbed onto zinc oxide to measure various effects of surface polarity. The experimental findings showed that the adsorption mechanism of PVFA and PVFA-co-PVAm strongly depends on the degree of hydrolysis of PVFA and pH values and also on the kind of metal or metal oxide surfaces that were employed as adsorbents. The adsorption mechanism of PVFA/PVFA-co-PVAm onto zinc oxide and iron oxide surfaces is mainly affected by electrostatic interactions. Particularly in the region of pH 5, the adsorption of PVFA/PVFA-co PVAm onto zinc and iron metal particles is additionally influenced by redox processes, dissolution, and complexation reactions. PMID- 22074184 TI - Fatalities in wild goats in Kurdistan associated with Peste des Petits Ruminants virus. AB - Between August 2010 and February 2011, over 750 deaths were recorded among wild goats (Capra aegagrus, the endangered progenitor of the domestic goat) in Kurdistan. Based on the clinical signs and post-mortem findings, the involvement of peste des petits ruminants virus (PPRV) was suspected. This was confirmed by laboratory analysis, and the virus was found to be closely related to a Turkish strain isolated in 2000. During the outbreak in wild goats, no disease in domestic animals was reported. Domestic ruminants in the region are routinely vaccinated with an attenuated vaccine based on the 'Nigeria/75/1' strain of PPRV. This is the first report of active PPRV infection in Kurdistan and most likely the immunity afforded by vaccination prevented spillover infections. It is therefore recommended to continue with the campaign. Conversely, there is no justification for the use of force to keep the endangered wild goats away from domestic flocks. PMID- 22074185 TI - The effect of different criteria on the number of patients blind from open-angle glaucoma. AB - BACKGROUND: The prevalence of blindness and visual impairment from glaucoma is influenced by the criteria used to define these entities, which differ between countries and regions, as well as among published reports. The objective of the present study was to ascertain the extent to which different criteria of blindness and visual impairment influence estimates of the number of patients classified as blind or visually impaired by glaucoma in a clinic-based population. METHODS: We conducted a retrospective chart review of 914 patients with open-angle glaucoma to compare numbers of patients identified as visually impaired with and without considering visual field status. We also compared proportions classified using World Health Organisation (WHO) and United States (US) blindness criteria, and applying a new US Social Security Administration (SSA) disability criterion: perimetric mean deviation (MD) <= -22 dB. RESULTS: Forty patients (4.4%) were bilaterally blind from glaucoma by the WHO criteria. Fifty-two (5.7%) were blind by the the US criterion. Assessing only visual acuity, 14 (1.5%) patients were blind by the WHO criteria and 24 (2.6%) by the US definition. Eighty-five (9.3%) met the US SSA disability criterion. Among those, 52 were impaired also by the WHO definition. No patients impaired according to the WHO criteria had MD values better than -22 dB. CONCLUSIONS: Excluding visual field status will seriously underestimate the prevalence of glaucoma blindness. In our patient population, 30% more patients were classified as blind by the US than by the WHO definition. Also, 60% more were identified as visually impaired by the US SSA criterion than by the WHO criteria. Visual field assessment is vital to determine visual impairment caused by glaucoma. PMID- 22074186 TI - Nanoscale analysis of the interaction between cyanoacrylate and vacuum metal deposition in the development of latent fingermarks on low-density polyethylene. AB - Vacuum metal deposition (VMD) has been previously demonstrated as an effective development technique for latent fingermarks and in some cases has been shown to enhance prints developed with cyanoacrylate (CA) (superglue) fuming. This work utilizes scanning electron microscopy (SEM) to investigate the interactions of the two development techniques when applied to latent fingermarks on low-density polyethylene. CA is shown to act principally on the eccrine deposits around sweat pores, where polymerization results in long polymer fibrils a few 100 nm in width. Subsequent VMD processing results in additional areas of development, for example, between pores. However, the primary mode of deposition of zinc is by interaction with the polymerized CA, the fibrils of which become decorated with zinc nanoparticles. Areas with limited CA deposition and no significant polymerization are also enhanced with the VMD process, resulting in increased print development. PMID- 22074187 TI - Molecular rotation in self-assembled multidecker porphyrin complexes. AB - An alkyl chain-substituted multidecker porphyrin (a cerium double-decker porphyrin (CeDDP) and a lanthanum triple-decker porphyrin (LaTDP)) complexes were arranged in a monolayer array on Au(111) substrate. By using a pulse injection deposition method, both multidecker complexes were deposited on the surface intact to form a well-defined two-dimensional array. Low-temperature scanning tunneling microscopy (STM) allowed the measurement of the topographic heights of the multidecker porphyrin complexes and visualization of their internal structures clearly. The STM images suggest that the top porphyrin ligand in CeDDP rarely rotates under nondestructive imaging condition, while the top porphyrin ligand in LaTDP exhibits flip-flop rotation even under the nondestructive imaging condition at sub-pA tunneling currents. These results provide the future applications of molecular-scale mechanical machines and single molecule storage memory. PMID- 22074188 TI - Linezolid versus vancomycin antibiotic lock solution for the prevention of nontunneled catheter-related blood stream infections in hemodialysis patients: a prospective randomized study. AB - The use of antibiotic lock solutions (ALSs) for the prevention of catheter related blood stream infections (CRBSIs) is a promising option. The efficacy and safety of linezolid as ALS were evaluated in a randomized double-blind prospective study where 131 patients who required nontunneled catheter (NTC) for hemodialysis (HD) were randomized to receive an ALS with either (A) unfractionated heparin (2000 U/ml) alone as a catheter lock control, (B) vancomycin (5 mg/ml) + heparin (2000 U/ml), or (C) linezolid (2 mg/ml) + heparin (2000 U/ml). The primary endpoint of the study was CRBSI. A total of 152 NTCs were inserted in 131 patients. The linezolid-locked group did not present any infective episode (CRBSI rate = 0/1000 catheter days) compared with 2 episodes in the vancomycin-locked group (CRBSI rate = 1.21/1000 catheter days, p = 0.1021) and 11 episodes in the heparin-locked group (CRBSI rate = 6.7/1000 catheter days, p = 0.0001). Median number of catheter days was greater in group C (median = 38) compared with group B (median = 36, p = 0.0415) and with group A (median = 34, p = 0.0036). No side effects and no resistant organisms were recorded with the use of linezolid ALS. Linezolid appears to be a safe and effective ALS, preventing CRBSI and prolonging the survival of the catheter in HD patients. PMID- 22074189 TI - Expression of chemosensory proteins in the tsetse fly Glossina morsitans morsitans is related to female host-seeking behaviour. AB - Chemosensory proteins (CSPs) are a class of soluble proteins present in high concentrations in the sensilla of insect antennae. It has been proposed that they play an important role in insect olfaction by mediating interactions between odorants and odorant receptors. Here we report, for the first time, the presence of five CSP genes in the tsetse fly Glossina morsitans morsitans, a major vector transmitting nagana in livestock. Real-time quantitative reverse transcription PCR showed that three of the CSPs are expressed in antennae. One of them, GmmCSP2, is transcribed at a very high level and could be involved in olfaction. We also determined expression in the antennae of both males and females at different life stages and with different blood feeding regimes. The transcription of GmmCSP2 was lower in male antennae than in females, with a sharp increase in 10-week-old flies, 48 h after a bloodmeal. Thus there is a clear relationship between CSP gene transcription and host searching behaviour. Genome annotation and phylogenetic analyses comparing G. morsitans morsitans CSPs with those of other Diptera showed rapid evolution after speciation of mosquitoes. PMID- 22074190 TI - Ethnicity predicts perceptions of smoking and smoking cessation among veterans. AB - The objective of this study was to determine if race/ethnicity predicts motivation to quit smoking and preferences for cessation services among smokers serviced by a primarily psychiatric Veterans Affairs hospital. A self administered survey was given to a convenience sample of smokers (n=146) at the Battle Creek Veterans Affairs Medical Center. Univariate, bivariate and multivariate regression analyses were calculated to determine the association between race/ethnicity and motivation to quit smoking. Forty-two per cent of the sample was non-white. Non-white patients smoked significantly less cigarettes per day as compared with white patients (P=0.002). In the multivariate analyses, compared with whites, non-whites had 3.5 times greater odds of thinking that quitting smoking was extremely/very important to health (P= 0.01), 4.0 times greater odds of thinking of quitting using tobacco products in the next 30 days (P=0.004) and 3.4 times greater odds of being interested in receiving smoking cessation services (P=0.007). Yet, non-white patients were less likely to be interested in intensive nurse counselling and cessation medications. As the number of non-whites continues to increase in the military, novel strategies may be needed to capitalize on the high motivation to quit smoking and preference for non-traditional interventions among non-white smokers treated in Veterans Affairs hospitals. PMID- 22074191 TI - Laparoscopic low anterior resection for hematogenous rectal metastasis from gastric adenocarcinoma: a case report. AB - BACKGROUND: Gastric cancer is one of the most common malignancies in the world and is the second most common cause of cancer-related death in Korea. Colorectal metastases from gastric adenocarcinoma are known to be very rare. We report an unusual case of rectal metastasis of gastric adenocarcinoma. CASE PRESENTATION: We report a case of a 43-year-old female patient with gastric cancer who first presented with epigastric pain. The endoscopic and radiologic findings were suggestive of Borrmann type III advanced gastric cancer with linitis plastica. Radical total gastrectomy with D2 lymph node dissection was performed. The pathology report was AJCC TNM Stage II gastric adenocarcinoma (T3N0M0). On follow up at 34 months after surgery, the patient complained of difficulty in defecation. On colonoscopy, a hard, indurated extraluminal mass was detected 7 cm proximal to the anal verge. The biopsy demonstrated chronic nonspecific colitis. Abdominal CT, rectal MRI and PET-CT revealed rectal metastasis from gastric cancer. Laparoscopic ultralow anterior resection with diverting ileostomy was performed. The pathology report was metastatic adenocarcinoma, and this diagnosis was identical to the gastric pathology reported in the previous pathology report. The patient was discharged after the 11th postoperative day with no adverse events. CONCLUSION: Rectal metastasis from gastric cancer is known to be very rare. However, metastatic gastric adenocarcinoma should be considered as a differential diagnosis for patients presenting with a colorectal mass and a past history of gastric cancer. PMID- 22074192 TI - Staphylococcus aureus infection induced redox signaling and DNA fragmentation in T-lymphocytes: possible ameliorative role of nanoconjugated vancomycin. AB - Staphylococcus aureus is most frequently isolated pathogen causing bloodstream infections, skin and soft tissue infections and pneumonia. Vancomycin sensitive and resistant S. aureus infection causes oxidative stress in neutrophils and lymphocytes. Lymphocyte is an important immune cell. The immune cells use reactive oxygen species (ROS) for carrying out their normal functions while an excess amount of ROS can attack cellular components that lead to cell damage. The aim of the present study was to test the protective role of nanoconjugated vancomycin against Vancomycin Sensitive S. aureus (VSSA) and Vancomycin Resistant S. aureus (VRSA) infection induced oxidative stress in T-lymphocytes. VSSA and VRSA infection were developed in Swiss mice by intraperitoneal injection of 5 * 10(6) CFU/ml bacterial solutions. Nanoconjugated vancomycin was treated to VSSA and VRSA infected mice at a dose of 100 mg/kg bw/day and 500 mg/kg bw/day, respectively for successive 10 days. Vancomycin was treated to VSSA and VRSA infected mice at similar dose, respectively, for 10 days. The result of this study reveals that in vivo VSSA and VRSA infection significantly increases the level of nitrite generation, lipid peroxidation, protein oxidation, oxidized glutathione level, DNA fragmentation, and decreases the level of reduced glutathione, antioxidant enzyme status, glutathione dependent enzymes as compared to control group; which were increased or decreased significantly near to normal in T-lymphocytes of nanoconjugated vancomycin treated group. These finding suggests the potential use and beneficial protective role of nanoconjugated vancomycin against VSSA and VRSA infection induced oxidative stress in T lymphocytes. PMID- 22074193 TI - G-protein betagamma subunits in vasorelaxing and anti-endothelinergic effects of calcitonin gene-related peptide. AB - BACKGROUND AND PURPOSE: Calcitonin gene-related peptide (CGRP) has been proposed to relax vascular smooth muscle cells (VSMC) via cAMP and can promote dissociation of endothelin-1 (ET-1) from ET(A) receptors. The latter is not mimicked by other stimuli of adenylate cyclases. Therefore, we evaluated the involvement of G-protein betagamma subunits (Gbetagamma) in the arterial effects of CGRP receptor stimulation. EXPERIMENTAL APPROACH: To test the hypothesis that instead of alpha subunits of G-proteins (Galphas), Gbetagamma mediates the effects of CGRP receptor activation, we used (i) rat isolated mesenteric resistance arteries (MRA), (ii) pharmacological modulators of cyclic nucleotides; and (iii) low molecular weight inhibitors of the functions of Gbetagamma, gallein and M119. To validate these tools with respect to CGRP receptor function, we performed organ bath studies with rat isolated MRA, radioligand binding on membranes from CHO cells expressing human CGRP receptors and cAMP production assays in rat cultured VSMC. KEY RESULTS: In isolated arteries contracted with K(+) or ET-1, IBMX (PDE inhibitor) increased sodium nitroprusside (SNP)- and isoprenaline (ISO)- but not CGRP-induced relaxations. While fluorescein (negative control) was without effects, gallein increased binding of [(125) I]-CGRP in the absence and presence of GTPgammaS. Gallein also increased CGRP-induced cAMP production in VSMC. Despite these stimulating effects, gallein and M119 selectively inhibited the relaxing and anti-endothelinergic effects of CGRP in isolated arteries while not altering contractile responses to K(+) or ET-1 or relaxing responses to ISO or SNP. CONCLUSION AND IMPLICATIONS: Activated CGRP receptors induce cyclic nucleotide-independent relaxation of VSMC and terminate arterial effects of ET-1 via Gbetagamma. PMID- 22074194 TI - The relationship between attitudes towards different containment measures and their usage in a national sample of psychiatric inpatients. AB - The aims of this report were to explore the relationships between patients' approval of containment measures, their levels of usage and patients' individual experience of each measure. Additionally the psychometric properties of the Attitudes to Containment Measures Questionnaire (ACMQ) were tested. A cross sectional design was used. The ACMQ was completed by 1361 patients across 136 acute psychiatric wards from three regions in England that participated in the 'City 128' study. Staff on each ward completed the Patient-Staff Conflict Checklist - Shift Report at the end of each shift to log how often each containment measure was used. Frequency of patient reported containment correlated with rates reported by staff. Patients had separate attitudes to each containment measure rather than an attitude towards containment in general. High frequency of coerced intramuscular (IM) medication use was associated with negative attitudes to nearly all types of containment. The ACMQ has good construct validity. In wards where high levels of IM medication are used, all patients have lower approval ratings for a number of other containment measures. This suggests that IM medication has a negative impact not only on those subjected to it but also patients who witness it. Measures to reduce the negative impact of IM medication are discussed. PMID- 22074197 TI - Changes in the use of birth control methods. AB - Abstract Information on changes in the methods of contraception used was collected from women in a KAP Survey of Trinidad and Tobago in 1970-71. Using methods analagous to those used in the study of internal migration, it is found that 54% of contraceptors were still using the method they first used, and 46% had changed. In general, the net changes tended to be from less to more efficient methods. This is demonstrated with data showing: 1. the number of changes from one method to another; 2. the number of changes these women have made, considering the first and last methods only; and 3. the number of changes, including intermediate changes. Nevertheless, there is also an appreciable movement away from the more effective methods either to other methods, or out of contraceptive practice entirely. The rate of dropout from contraception has been increasing in recent years for all methods, and, apparently, for all ages of women. The principal reasons given for stopping the use of the various methods were: 1. pregnancy; 2. that the method was uncomfortable or too much trouble; 3. that the method made the user ill (in the case of the pill and the IUD); and 4. that the partner disliked the method (in the case of the condom and withdrawal). More positive reasons include: 1. that the woman wanted more children; and 2. that she no longer had a partner. PMID- 22074198 TI - The concept and measurement of child dependency: An approach to family formation analysis. AB - Abstract Two distinctions appear crucial in the study of human fertility: (1) aggregate versus individuallevel analysis; and (2) true explanations versus 'demographic explanations', using Stinchcombe's terminology. Social demographers analysing fertility have been accustomed to using fertility measurements derived from aggregative population analyses, and have largely terminated their analytic efforts at the level of a 'demographic explanation'. The failure to arrive at a social analysis of the process of fertility decision-making may in part to be due to this measurement heritage, which may be inappropriate for individual-level analyses. As a first step in the direction of creating measurement suitable for such analyses, fertility decision-making is labelled as family formation decision making, and this is linked to the concept of child dependency. Measures of child years-of-dependency (CYD) are proposed for use in family formation analysis. These integrate current quantity and tempo measures, and have greater potential for use at the level ofthe family. They require no additional data beyond fertility histories, are flexible in terms of non-modal family situations (e.g. divorce, infant or child mortality) and may be indicators of criteria used by couples in planning their fertility. Refinements of the basic CYD measures are explored. These include analyses of average versus marginal costs of child rearing, age gradients of costs and social class differentials in costs. All of these are intended to make CYD measures more useful in individual cost-benefit analyses of child-bearing and child-rearing. PMID- 22074199 TI - Assessment of family planning programme effects on births: Preliminary results obtained through direct matching of birth and programme acceptor records. AB - Abstract In order to match birth and family planning acceptance records and thereby to obtain estimates of pre- and post-acceptance fertility, use is made of seven-digit national identity card numbers, issued to all adult West Malaysians. These unique numbers are recorded on live-birth records and national family planning programme acceptor records of West Malaysian women. The application and preliminary results of this method of direct computer matching of these sets of records for assessing the effects of a family planning programme on fertility are described. Pre- and post-acceptance fertility rates are presented in terms of contraceptive methods used, and the key characteristics of race and age of programme acceptors, and are discussed in terms of marital duration and number of children at the time of acceptance. PMID- 22074195 TI - Weight loss and African-American women: a systematic review of the behavioural weight loss intervention literature. AB - The excess burden of obesity among African-American women is well documented. However, the behavioural weight loss intervention literature often does not report results by ethnic group or gender. The purpose of this article is to conduct a systematic review of all behavioural weight loss intervention trials published between 1990 and 2010 that included and reported results separately for African-American women. The criteria for inclusion included (i) participants age >=18 years; (ii) a behavioural weight loss intervention; (iii) weight as an outcome variable; (iv) inclusion of African-American women; and (v) weight loss results reported separately by ethnicity and gender. The literature search identified 25 studies that met inclusion criteria. Our findings suggest that more intensive randomized behavioural weight loss trials with medically at-risk populations yield better results. Well-designed and more intensive multi-site trials with medically at-risk populations currently offer the most promising results for African-American women. Still, African-American women lose less weight than other subgroups in behavioural weight loss interventions. It is now critical to expand on individual-level approaches and incorporate the biological, social and environmental factors that influence obesity. This will help enable the adoption of healthier behaviours for this group of women disproportionately affected by obesity. PMID- 22074200 TI - Temporal and spatial analysis of fertility decline in Taiwan. AB - Abstract The conventional mode of evaluating the success of family planning programmes has frequently emphasized the activities of the programmes, rather than their ultimate effects. This paper examines the role of family planning programmes in inducing fertility decline in Taiwan. First it presents the secular trends of Taiwanese fertility changes, pointing out that family planning programmes began only after the birth rate had already shown a substantial decline. Secondly, it specifically evaluates the impact of family planning programmes in the Taichung areas, since its success has been widely proclaimed. Finally, it is stipulated that the dynamics of Taiwanese fertility changes may be related to declining infant mortality and accelerating educational development, and that these institutional effects, rather than the family planning programmes, should be credited with changes in fertility. PMID- 22074201 TI - Relation of marriage and education to fertility in the U.S.S.R. AB - Abstract One-half of the variation in Soviet fertility as measured by the child woman ratio is attributable to the proportion of married women in the 20-24 age group. The familar sociological hypothesis of an inverse relation between human fertility and education also is fully substantiated with data for the 36 major ethnic groups in the U.S.S.R. The second and third best predicting variables fall into the two extreme age groups: (a) those 16 to 19 years of age with more than seven years of school completed and (b) those men and women aged 60 and over with the equivalent formal education. Results of this study support the modified hypothesis that complements previously publicized findings. It asserts that variations in fertility attributable to the traditionally religious values can be explained in terms of the age-specific marriage and educational differentials known to have existed in the past and still characteristic of the multi-national society in the Soviet Union. PMID- 22074202 TI - The fertility of negroes without southern rural experience: A re-examination of the 1960 GAF study findings with 1967 SEO Data. AB - Abstract A major finding of the 1960 'Growth of American Families' (GAF) study was that whites and blacks without southern rural experience had similar fertility. This paper reports on a re-examination of this finding with a substantially larger black sample. Data from the 1967 Survey of Economic Opportunity demonstrated that the residence background classification utilized in the GAF study defeated, in part, the attempt to remove the effects of rural experience on fertility. Indigenous urban blacks had 25% higher fertility than indigenous urban whites. The fertility of urban black migrants out of the rural South was sharply curtailed in contrast to those remaining in the rural South. Although urban blacks of southern rural background had nominally higher fertility than indigenous urban blacks, the difference was neither statistically nor substantively significant. These results demand a re-ordering of the interpretation of the impact that migration has on urban black fertility and the white-black differential in fertility. PMID- 22074203 TI - The influence of cause-specific mortality conditions on the age pattern of mortality with special reference to Taiwan. AB - Abstract This paper discusses the relationship between the level of mortality at ages one to four, on one hand, and five to 34 on the other. This relationship has been observed to vary considerably among mortality schedules at different levels of mortality and even among schedules at the same general level of mortality. This variation is shown among the modem life table systems of the Regional Model Life Tables and the United Nations Model Life Tables. Controlling for the leyel ofmortality from age five to age 34, the West Tables and the United Nations Tables embody approximately the same 'average' relationship between early childhood and adult mortality. Relatively to this average relationship, the South and East Tables consistently display higher childhood mortality rates for a given level of adult mortality. Indeed, the childhood rates of the South Table are twice those of the West Tables over a range of life expectancy at birth from 40 to 70 years. The relationship between childhood and adult mortality from 1957 to 1968, a period of rapid mortality decline, was investigated in Taiwan. In 1957, the Taiwanese data reflected the severe childhood mortality of the South Model Tables. However, by 1968, due to an especially large decline in childhood mortality, this relationship was more moderate and resembled the mortality pattern of the West or East Model Tables. An analysis of the decline in cause specific mortality during the period revealed that a dramatic decline in childhood mortality from gastro-enteritis was primarily responsible for the shift in the relationship between childhood and adult mortality in Taiwan. It is asserted that, while any of several diseases which result in fatalities primarily among children of pre-school ages, could cause relatively severe childhood mortality, gastro-enteritis is likely to be a primary contributor to such an age pattern. This assertion is based on the fact that, especially in the developing areas of the world, malnutrition and gastro-enteritis are usually precipitating and complicating factors of other childhood diseases. A limited test of this hypothesis was provided by considering the causal components of childhood mortality rates in two populations known, for certain periods, to have exhibited relatively severe childhood mortality conditions; Spain and Portugal. For the years in which those populations were characterized by the South mortality pattern, gastro-enteritis was a principal cause of mortality in childhood. Moreover, with the decline in mortality from gastro-enteritis, the mortality pattern in Spain and Portugal no longer exhibited childhood mortality rates which were severe relative to those of adult life. The implications of these findings for the analysis of mortality conditions in many areas of the developing world, where the gastro-enteritis malnutrition syndrome annually claims a heavy toll of life in early childhood, are not clear. In those areas, the effect of this syndrome on the age pattern of mortality could be offset by special conditions inflating adult mortality rates. Nevertheless, in circumstances where there is evidence indicating substantial childhood mortality from this syndrome and no evidence indicating compensating severe adult mortality, there is reason to suspect that the existing mortality pattern reflects the relatively severe childhood mortality conditions of the South Model Tables. Additionally, where mortality from the gastro-enteritis malnutrition syndrome has been severe in past years, but has been reduced to low levels in recent years, it is probable that the relationship between childhood and adult mortality will shift in favour of the former - quite possibly, in the manner of Taiwan, from a South to an East or West age pattern. PMID- 22074204 TI - On the pattern of cohort fertility. AB - Abstract An examination of the patterns of cohort fertility rates in a number of populations revealed the existence of a common pattern showing how mean family sizes of the different age-at-marriage groups of a given marriage cohort are built up over the reproductive span. Standard schedules of fertility patterns are generated by the use of the Gompertz function which defines the distribution of cumulative fertility rates of a given marriage cohort by marriage duration by means of only three parameters. The generated system is tested with the historical series for England and Wales and Sweden and is found adequate to describe widely different childbearing patterns. Some of the demographic implications of the existence of common fertility patterns are examined and the usefulness of the generated system in projecting future fertility trends is briefly discussed. PMID- 22074206 TI - Justifying discrimination against Muslim immigrants: out-group ideology and the five-step social identity model. AB - This study examines how Geert Wilders, leader of the far-right Party For Freedom (PVV) in the Netherlands, justifies discriminatory measures for Muslim citizens. Wilders' contributions to four parliamentary debates and newspaper articles are analysed. The analysis shows that Wilders consistently makes a distinction between Islam as a belief system and Muslims as a group of people. Islam is defined as external to the West and as a major threat to the virtuous nature of the in-group. Defending and preserving Western liberal values against Islam is construed as a moral imperative. It is further shown how the distinction between Islam and Muslims functions to ward off accusations of prejudice and discrimination. It is concluded that social psychologists studying prejudice and discrimination should pay more attention to the distinction between person categories and ideological categories, and to political leadership. PMID- 22074207 TI - Speciation and degradation of triphenyltin in typical paddy fields and its uptake into rice plants. AB - Triphenyltin (TPhT) is a biocide used worldwide in agriculture, especially in rice crop farming. The distribution and dissipation of TPhT in rice fields, as well as uptake of TPhT and other phenyltin compounds (monophenyltin, MPhT, and diphenyltin, DPhT) is still unknown at present. In this study, speciation analysis of phenyltin compounds was carried out in soil and water from a rice field where TPhT was applied during rice seeding according to legal application rates in Brazil. The results indicate the degradation of biocide and distribution of tin species into soil and water. To evaluate whether TPhT is taken up by plants, rice plants were exposed to three different TPhT application rates in a controlled mesocosm during 7 weeks. After this period, tin speciation was determined in soil, roots, leaves, and grains of rice. Degradation of TPhT was observed in soil, where DPhT and MPhT were detected. MPhT, DPhT, and TPhT were also detected in the roots of plants exposed to all TPhT application rates. Only TPhT was detected in leaves and at relatively low concentration, suggesting selective transport of TPhT in the xylem, in contrast to DPhT and MPhT. Concentration of phenyltin species in rice grains was lower than the limit of detection, suggesting that rice plants do not have the capability to take up TPhT from soil and transport it to the grains. PMID- 22074208 TI - Disparities in reproductive health-related visits to the emergency department in Maryland by age and race, 1999-2005. AB - OBJECTIVE: To describe reproductive health-related visits to Maryland emergency departments (EDs) among women aged 15-44 years from 1999 to 2005. METHODS: We obtained data from the Healthcare Cost and Utilization Project State Emergency Department Database and State Inpatient Database. ICD-9-CM diagnosis codes were used to classify reproductive health-related visits. We calculated the annual rate of reproductive health visits to Maryland EDs from 1999 to 2005 for women aged 15-44 years and tested time trends using linear regression. Admission rates were defined as the percentage of ED visits that resulted in inpatient admission. We calculated age-specific and race-specific rate ratios for diagnoses using Poisson regression and admission rate ratios using Cochran-Mantel-Haenszel statistics. RESULTS: From 1999 to 2005, the rate of ED visits in Maryland increased 50%, from 28.0 to 42.1 visits per 1000 women. Lower genital tract infections were the most common diagnosis (21.4%). The rates were higher for women aged 15-24 than for women aged 25-44 (rate ratio 1.18, 95% confidence interval [CI] 1.17-1.18) and nearly three times higher for black women than white women (rate ratio 2.94, 95% CI 2.92-2.96). Admission rates were lower for women aged 15-24 than for women aged 25-44 (rate ratio 0.34, 95% CI 0.33-0.35) and were higher among black than white women (rate ratio 1.16, 95% CI 1.14-1.18). CONCLUSIONS: Disparities by age and race are evident for reproductive health related ED visits in Maryland, and many of these ED visits are for conditions that are amenable to preventive measures. PMID- 22074209 TI - The perceived need for Japanese nursing faculty members to learn English: issues related to career development. AB - In Japan, nurses are increasingly expected to use English in various settings. English language proficiency is indispensable in almost all aspects of the clinical experience and for career development of Japanese nurses. This article introduces the idea of Japanese nurses learning the English language to enhance their career development and provides succinct survey results about the perceived need for learning English, based on responses from 145 nursing faculty members across Japan. Analyses showed that most faculty members considered English language proficiency important for nursing expertise and career development. Overall, the results indicated that Japanese nurses require continuing English language education. Further study of their need to learn English and ways to implement English education programs is required. PMID- 22074210 TI - The effect of high-fidelity patient simulation on the critical thinking and clinical decision-making skills of new graduate nurses. AB - This study was conducted to determine whether the addition of high-fidelity patient simulation to new nurse orientation enhanced critical thinking and clinical decision-making skills. A pretest-posttest design was used to assess critical thinking and clinical decision-making skills in two groups of graduate nurses. Compared with the control group, the high-fidelity patient simulation group did not show significant improvement in mean critical thinking or clinical decision-making scores. When mean scores were analyzed, both groups showed an increase in critical thinking scores from pretest to posttest, with the high fidelity patient simulation group showing greater gains in overall scores. However, neither group showed a statistically significant increase in mean test scores. The effect of high-fidelity patient simulation on critical thinking and clinical decision-making skills remains unclear. PMID- 22074211 TI - Practice makes perfect: tips for successful institutional review board submissions. AB - As the nursing profession seeks to develop evidence-based practice, nurses are being encouraged to embark on research in their institutions. Staff nurses and nurse clinicians often struggle with the process of obtaining institutional review board approval for their projects. When classes are available, the focus is frequently on informing nurses about the federal regulations for protection of human subjects. This article addresses practical strategies for addressing these regulations from the perspective of both the individual nurse and the nursing leader. PMID- 22074212 TI - Taking charge: front-line nurse leadership development. AB - The recent Institute of Medicine (2010) report, The Future of Nursing: Leading Change, Advancing Health, included a recommendation that nurses at all levels should be prepared and enabled to lead change to advance health care in the United States. Historically, in most organizations, nursing leadership development programs have focused on nurses in management or executive roles rather than those working in front-line leadership roles. This article describes a front-line leadership development initiative developed by Tenet Healthcare Corporation and attended by 400 charge nurses. Program development, evaluation, and lessons learned that can be applied in other organizations are discussed. PMID- 22074213 TI - Meeting tomorrow's health care needs through local and global involvement. AB - Strengthened efforts to achieve the United Nations Millennium Development Goals by 2015 are urgently needed. A fundamental step toward achieving these goals is strengthening global partnerships for development. This article describes critical challenges and opportunities in global health and the social responsibility of the nursing profession in this area. Examples and suggestions for nursing action are provided for consideration by those interested in influencing global health. Engaging in global health activities such as study abroad programs, interprofessional exchanges, continuing education workshops, and seminars with a global health focus can have significant implications for nursing education, research, policy, and practice. Equipping nurses with the leadership skills, knowledge, and attitudes needed to advance global health is integral in the delivery of effective, culturally relevant health care. PMID- 22074214 TI - Development of a hybrid simulation course to reduce central line infections. AB - Clinical educators are continually looking at ways to effectively deliver large amounts of information to their learners. Whether as a part of pre-course work or as a separate phase of training, there are numerous benefits to making information available to learners before conducting sessions that allow the learners to practice the skills. Hybrid courses consist of a mixture of online and on-site instruction and offer a viable option for clinical educators to consider, especially when their intended audience consists of thousands of learners. This article describes the experiences of a medical simulation center and the use of a hybrid curriculum technique to reduce central line infections. PMID- 22074215 TI - Characteristics that perinatal nurse managers desire in new nurse hires. AB - BACKGROUND: Nursing leaders have proposed that nurses must have the Quality and Safety Education for Nurses (QSEN) competencies to work in complex health care systems. Using the QSEN framework, this study explored what characteristics perinatal nurse managers desired most in new nurses. METHODS: This study used a survey design and a convenience sample of perinatal nurse managers working in Indiana hospitals (N = 46). RESULTS: Managers were more likely to hire nurses with experience, positive references, and excellent attendance. Of the QSEN competencies, managers looked most for teamwork and collaboration, followed by safety and patient-centered care. CONCLUSION: In addition to the traditional qualities desired in new nurses, the QSEN competencies are gaining importance among perinatal managers. PMID- 22074216 TI - Outcomes of a continuing education course on intravenous catheter insertion for experienced registered nurses. AB - Many experienced nurses report a lack of confidence in their intravenous (IV) catheter skills despite training with a phlebotomist and designated orientation time with the IV team. This study assessed the success of an IV catheter insertion continuing education class aimed at improving experienced nurses' skills levels, confidence, and knowledge regarding IV catheter insertion, maintenance, and infection prevention. Through a partnership between a hospital and a college of nursing continuing education program, a 1-day course was provided for 33 experienced nurses. The educators sought to determine whether a continuing education course improved the knowledge and skills of experienced nurses regarding the insertion of peripheral IV catheters and whether the nurses retained the knowledge and skills learned in a formal IV course over time. The findings showed that the continuing education IV course improved the knowledge and skills of experienced nurses. Improvement in knowledge was shown immediately after the course and 8 to 12 weeks later. Skills improvement with regard to infection prevention and policy adherence was evident. Because confidence data were collected with two different scales before and after the course, they were unusable for statistical testing. Further study is needed to determine whether nurses' confidence levels would improve after the implementation of a formal IV course. Replication studies are also needed to validate the results with a larger sample size. PMID- 22074217 TI - 4-Amino-6-hydroxypyrazolo [3,4-d]pyrimidine (AHPP) conjugated PEG micelles: water soluble polymeric xanthine oxidase inhibitor. AB - Xanthine oxidase (XO) is the major source of superoxide anion (O(2)(-)) that is associated with various reactive oxygen species (ROS) related diseases. 4-amino-6 hydroxypyrazolo[3,4-d]pyrimidine (AHPP) is a potent XO inhibitor discovered in Maeda's laboratory, which is now being developed for the treatment of ischemia reperfusion injury and inflammatory diseases. However, the poor aqueous solubility of AHPP at physiological pH hampers its clinical development. To overcome this drawback, in the present study water soluble polyethyleneglycol conjugated AHPP (AHPP-PEG) was synthesized via two different approaches, which resulted in two derivatives of AHPP-PEG, namely, mono-AHPP-PEG and bis-(AHPP)-PEG depending on the number of AHPP on PEG chain. We characterized both conjugates by UV, FTIR spectroscopy and elemental analysis. Dynamic light scattering and Sephadex G-100 chromatography studies revealed mean particle size of 164.1 and 218.8 nm and Mw. equivalent to 107 and 126 kDa for mono-AHPP-PEG and bis-(AHPP) PEG, respectively. Further, XO inhibitory activity for mono-AHPP-PEG and bis (AHPP)-PEG were found with Ki of 0.23+/-0.03 and 0.21+/-0.03 MUM, respectively. In vivo pharmacokinetic study showed longer circulation time of AHPP-PEG conjugates compared to free AHPP. These results indicate AHPP-PEG conjugates have better potentials with supramolecular assemblies in aqueous medium and may become a good candidate for the treatment of ROS related diseases. PMID- 22074218 TI - Methamphetamine-induced changes in the striatal dopamine pathway in MU-opioid receptor knockout mice. AB - BACKGROUND: Repeated exposure to methamphetamine (METH) can cause not only neurotoxicity but also addiction. Behavioral sensitization is widely used as an animal model for the study of drug addiction. We previously reported that the MU opioid receptor knockout mice were resistant to METH-induced behavioral sensitization but the mechanism is unknown. METHODS: The present study determined whether resistance of the MU-opioid receptor (MU-OR) knockout mice to behavioral sensitization is due to differential expression of the stimulatory G protein alpha subunit (Galphas) or regulators of G-protein signaling (RGS) coupled to the dopamine D1 receptor. Mice received daily intraperitoneal injections of saline or METH (10 mg/kg) for 7 consecutive days to induce sensitization. On day 11(following 4 abstinent days), mice were either given a test dose of METH (10 mg/kg) for behavioral testing or sacrificed for neurochemical assays without additional METH treatment. RESULTS: METH challenge-induced stereotyped behaviors were significantly reduced in the MU-opioid receptor knockout mice when compared with those in wild-type mice. Neurochemical assays indicated that there is a decrease in dopamine D1 receptor ligand binding and an increase in the expression of RGS4 mRNA in the striatum of METH-treated MU-opioid receptor knockout mice but not of METH-treated wild-type mice. METH treatment had no effect on the expression of Galphas and RGS2 mRNA in the striatum of either strain of mice. CONCLUSIONS: These results indicate that down-regulation of the expression of the dopamine D1 receptor and up-regulation of RGS4 mRNA expression in the striatum may contribute to the reduced response to METH-induced stereotypy behavior in MU opioid receptor knockout mice. Our results highlight the interactions of the MU opioid receptor system to METH-induced behavioral responses by influencing the expression of RGS of dopamine D1 receptors. PMID- 22074219 TI - Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. AB - BACKGROUND: A significant reduction in parasite clearance rates following artesunate treatment of falciparum malaria, and increased failure rates following artemisinin combination treatments (ACT), signaled emergent artemisinin resistance in Western Cambodia. Accurate measurement of parasite clearance is therefore essential to assess the spread of artemisinin resistance in Plasmodium falciparum. The slope of the log-parasitaemia versus time relationship is considered to be the most robust measure of anti-malarial effect. However, an initial lag phase of numerical instability often precedes a steady exponential decline in the parasite count after the start of anti-malarial treatment. This lag complicates the clearance estimation, introduces observer subjectivity, and may influence the accuracy and consistency of reported results. METHODS: To address this problem, a new approach to modelling clearance of malaria parasites from parasitaemia-time profiles has been explored and validated. The methodology detects when a lag phase is present, selects the most appropriate model (linear, quadratic or cubic) to fit log-transformed parasite data, and calculates estimates of parasite clearance adjusted for this lag phase. Departing from previous approaches, parasite counts below the level of detection are accounted for and not excluded from the calculation. RESULTS: Data from large clinical studies with frequent parasite counts were examined. The effect of a lag phase on parasite clearance rate estimates is discussed, using individual patient data examples. As part of the World Wide Antimalarial Resistance Network's (WWARN) efforts to make innovative approaches available to the malaria community, an automated informatics tool: the parasite clearance estimator has been developed. CONCLUSIONS: The parasite clearance estimator provides a consistent, reliable and accurate method to estimate the lag phase and malaria parasite clearance rate. It could be used to detect early signs of emerging resistance to artemisinin derivatives and other compounds which affect ring-stage clearance. PMID- 22074220 TI - Quantum phase transition from superparamagnetic to quantum superparamagnetic state in ultrasmall Cd(1-x)Cr(II)(x)Se quantum dots? AB - Despite a long history of success in formation of transition-metal-doped quantum dots (QDs), the origin of magnetism in diluted magnetic semiconductors (DMSs) is yet a controversial issue. Cr(II)-doped II-VI DMSs are half-metallic, resulting in high-temperature ferromagnetism. The magnetic properties reflect a strong p-d exchange interaction between the spin-up Cr(II) t(2g) level and the Se 4p. In this study, ultrasmall (~3.1 nm) Cr(II)-doped CdSe DMSQDs are shown to exhibit room-temperature ferromagnetism, as expected from theoretical arguments. Surprisingly, a low-temperature phase transition is observed at 20 K that is believed to reflect the onset of long-range ordering of the single-domain DMSQD. PMID- 22074221 TI - Expanding the optical trapping range of lipid vesicles to the nanoscale. AB - Small unilamellar lipid vesicles with diameters down to 50 nm enclosing high refractive index sucrose cores can be optically trapped individually in three dimensions using a focused laser beam. Combined optical trapping and confocal microscopy allows for simultaneous quantitative measurements of the forces exerted on individual vesicles and of their size and shape. The position of individual vesicles in three dimensions is measured with nanometer spatial and ~10 MUs temporal resolution. PMID- 22074222 TI - Isoflavonoids and coumarins from Glycyrrhiza uralensis: antibacterial activity against oral pathogens and conversion of isoflavans into isoflavan-quinones during purification. AB - Phytochemical investigation of a supercritical fluid extract of Glycyrrhiza uralensis has led to the isolation of 20 known isoflavonoids and coumarins, and glycycarpan (7), a new pterocarpan. The presence of two isoflavan-quinones, licoriquinone A (8) and licoriquinone B (9), in a fraction subjected to gel filtration on Sephadex LH-20 is due to suspected metal-catalyzed oxidative degradation of licoricidin (1) and licorisoflavan A (2). The major compounds in the extract, as well as 8, were evaluated for their ability to inhibit the growth of several major oral pathogens. Compounds 1 and 2 showed the most potent antibacterial activities, causing a marked growth inhibition of the cariogenic species Streptococcus mutans and Streptococcus sobrinus at 10 MUg/mL and the periodontopathogenic species Porphyromonas gingivalis (at 5 MUg/mL) and Prevotella intermedia (at 5 MUg/mL for 1 and 2.5 MUg/mL for 2). Only 1 moderately inhibited growth of Fusobacterium nucleatum at the highest concentration tested (10 MUg/mL). PMID- 22074225 TI - Friction between brush layers of charged and neutral bottle-brush macromolecules. molecular dynamics simulations. AB - Using molecular dynamics simulations, we study the lubricating properties of neutral and charged bottle-brush coatings as a function of the compression and shear stresses and brush grafting density. Our simulations have shown that in charged bottle-brush systems under shear there is a layer with excess counterions located in the middle between brush-bearing surfaces. The main deformation mode of the charged bottle-brush layers is associated with the backbone deformation, resulting in the backbone deformation ratio, alpha, and shear viscosity, eta, being universal functions of the Weissenberg number. In the case of neutral bottle-brush systems, in addition to the backbone deformation there is also side chain deformation. The coupling between backbone and side chain deformation violates universality in the deformation ratio, alpha, dependence on the Weissenberg number and results in scaling exponents varying with the compression stress and brush grafting density. The existence of different length scales controlling deformation of neutral bottle brushes manifests itself in the shear viscosity, eta, dependence on the shear rate, gamma. Shear viscosity, eta, as a function of the shear rate, gamma, has two plateaus and two shear thinning regimes. The low shear rate plateau and shear thinning regime correspond to the backbone deformation, while the second plateau and shear thinning regime at moderate shear rates are due to side chain deformation. For both systems the value of the friction coefficient increases with increasing shear rate. The values of the friction coefficient for charged bottle-brush systems are about ten times smaller than corresponding values for neutral systems at the same shear rate. PMID- 22074224 TI - Modulation of ion channels by hydrogen sulfide. AB - SIGNIFICANCE: Evidence of the ability of the gasotransmitter hydrogen sulfide (H(2)S) to serve as a regulator of many physiological functions, including control of blood pressure, regulation of cardiac function, protection of neurons, and cardiomyocytes against apoptosis, and in pain sensation is accumulating. However, the mechanisms accounting for its many actions are not yet well understood. RECENT ADVANCES: Following the pioneering studies of the regulation of N-methyl-d-aspartate receptors and ATP-sensitive K(+) channels by H(2)S, data continue to emerge indicating that H(2)S modulates other ion channel types. This article reviews the numerous, yet diverse, types of ion channels now reported to be regulated by H(2)S. CRITICAL ISSUES: Currently, a critical issue within this field is to determine the mechanisms by which H(2)S regulates ion channels, as well as other target proteins. Mechanisms to account for regulation include direct channel protein sulfhydration, channel redox modulation, effects mediated by interactions with other gasotransmitters (carbon monoxide and nitric oxide), and indirect effects, such as modulation of channel-regulating kinases. Through such modulation of ion channels, novel roles for H(2)S are emerging as important factors in both physiological and pathological processes. FUTURE DIRECTIONS: Increasing current awareness and understanding of the roles and mechanisms of action of ion channel regulation by H(2)S will open opportunities for therapeutic intervention with clear clinical benefits, and inform future therapies. In addition, more sensitive methods for detecting relevant physiological concentrations of H(2)S will allow for clarification of specific ion channel regulation with reference to physiological or pathophysiological settings. PMID- 22074223 TI - Phosphatidylinositol 3,4,5-trisphosphate activity probes for the labeling and proteomic characterization of protein binding partners. AB - Phosphatidylinositol polyphosphate lipids, such as phosphatidylinositol 3,4,5 trisphosphate [PI(3,4,5)P3], regulate critical biological processes, many of which are aberrant in disease. These lipids often act as site-specific ligands in interactions that enforce membrane association of protein binding partners. Herein, we describe the development of bifunctional activity probes corresponding to the headgroup of PI(3,4,5)P3 that are effective for identifying and characterizing protein binding partners from complex samples, namely cancer cell extracts. These probes contain both a photoaffinity tag for covalent labeling of target proteins and a secondary handle for subsequent detection or manipulation of labeled proteins. Probes bearing different secondary tags were exploited, either by direct attachment of a fluorescent dye for optical detection or by using an alkyne that can be derivatized after protein labeling via click chemistry. First, we describe the design and modular synthetic strategy used to generate multiple probes with different reporter tags of use for characterizing probe-labeled proteins. Next, we report initial labeling studies using purified protein, the PH domain of Akt, in which probes were found to label this target, as judged by in-gel detection. Furthermore, protein labeling was abrogated by controls including competition with an unlabeled PI(3,4,5)P3 headgroup analogue as well as through protein denaturation, indicating specific labeling. In addition, probes featuring linkers of different lengths between the PI(3,4,5)P3 headgroup and photoaffinity tag led to variations in protein labeling, indicating that a shorter linker was more effective in this case. Finally, proteomic labeling studies were performed using cell extracts; labeled proteins were observed by in-gel detection and characterized using postlabeling with biotin, affinity chromatography, and identification via tandem mass spectrometry. These studies yielded a total of 265 proteins, including both known and novel candidate PI(3,4,5)P3-binding proteins. PMID- 22074226 TI - Acute disseminated encephalomyelitis presenting as fever of unknown origin: case report. AB - BACKGROUND: Fever of unknown origin (FUO) can be defined as a body temperature higher than 38.3 degrees C on several occasions over more than 3 weeks, the diagnosis of which remains uncertain after 1 week of evaluation. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system with a wide range of clinical manifestations. The highest incidence of ADEM is observed during childhood and it usually occurs following a viral or bacterial infection or, more rarely, following a vaccination, or without a preceding cause. CASE PRESENTATION: Here, we describe an atypical case of ADEM that initially manifested as several weeks of FUO in a fifteen years old boy. CONCLUSIONS: This case report suggests a new possible syndromic association between ADEM and FUO, which should be considered in the clinical examination of patients with FUO, especially in the presence of also modest neurologic or neuropsychiatric symptoms. PMID- 22074228 TI - Using funnel plots in public health surveillance. AB - BACKGROUND: Public health surveillance is often concerned with the analysis of health outcomes over small areas. Funnel plots have been proposed as a useful tool for assessing and visualizing surveillance data, but their full utility has not been appreciated (for example, in the incorporation and interpretation of risk factors). METHODS: We investigate a way to simultaneously focus funnel plot analyses on direct policy implications while visually incorporating model fit and the effects of risk factors. Health survey data representing modifiable and nonmodifiable risk factors are used in an analysis of 2007 small area motor vehicle mortality rates in Alberta, Canada. RESULTS: Small area variations in motor vehicle mortality in Alberta were well explained by the suite of modifiable and nonmodifiable risk factors. Funnel plots of raw rates and of risk adjusted rates lead to different conclusions; the analysis process highlights opportunities for intervention as risk factors are incorporated into the model. Maps based on funnel plot methods identify areas worthy of further investigation. CONCLUSIONS: Funnel plots provide a useful tool to explore small area data and to routinely incorporate covariate relationships in surveillance analyses. The exploratory process has at each step a direct and useful policy-related result. Dealing thoughtfully with statistical overdispersion is a cornerstone to fully understanding funnel plots. PMID- 22074229 TI - Humeral and femoral head diameters in recent white American skeletons. AB - Osteologists often rely on single measurements, such as humeral and femoral head diameters, to estimate sex, especially when skeletons are incomplete. Measurements of 237 Bass Donated Collection skeletons provide a means of distinguishing white American females from males based on a modern sample: humeral head, female mean 42.1 mm, male mean 49.0 mm; and femoral head, female mean 42.2 mm, male mean 48.4 mm. Probabilities that bones at 1-mm increments came from females (p(f)) are estimated (p(m) = 1 - p(f)). An overrepresentation of one sex in the skeletons that are examined influences the probability that a bone of a certain size is from a female or male. So, probabilities are also estimated for samples consisting of an unequal number of males and females. Sample composition has its greatest effect when one sex dominates the remains that are the subject of investigation. PMID- 22074227 TI - Modest effect on plaque progression and vasodilatory function in atherosclerosis prone mice exposed to nanosized TiO(2). AB - BACKGROUND: There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease. METHODS: We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE(-/-)) mice exposed to TiO(2). ApoE(-/-) mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO2 (fTiO2, 288 nm), photocatalytic 92/8 anatase/rutile TiO(2) (pTiO(2), 12 nm), or rutile nano TiO(2) (nTiO(2), 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO(2) (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO(2)-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs). RESULTS: The exposure to nTiO(2) was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE(-/-) mice exposed to fine and photocatalytic TiO(2) had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO(2). CONCLUSION: Repeated exposure to nanosized TiO(2) particles was associated with modest plaque progression in ApoE(-/-) mice. There were no associations between the pulmonary TiO(2) exposure and inflammation or vasodilatory dysfunction. PMID- 22074230 TI - Patient dignity in psychiatric nursing practice. AB - Professional nurses have an ethical responsibility to protect and preserve the patients' dignity. The aim of this study was to describe how nurses experienced incidents relating to patients' dignity in a psychiatric nursing practice. A hermeneutic approach was used and data were collected using the critical incident technique. Data included 77 written critical incidents, which were interpreted by using a hermeneutic text interpretation. The findings show preserved dignity- caregivers have the courage to be present, and offended dignity - caregivers create powerlessness taken away by the patient. These findings show that patients' dignity in a psychiatric nursing practice can be preserved when caregivers act on their ethical responsibility. When patients' dignity is offended, the caregiver has become an inner value conflict, something they have been a part of against their own will. PMID- 22074231 TI - Catheter outcomes in the short-term inpatient setting: a controlled quality improvement study comparing citrate and heparin lock. AB - Heparin and citrate are used as catheter lock solutions to reduce risk of catheter dysfunction and infection in hemodialysis. There is a paucity of data comparing these two locks in the short-term, inpatient setting. We compared the efficacy of 2.2% acid citrate dextrose (ACD) versus 5000 U/ml heparin as catheter lock in the inpatient setting. The study was conducted at two sites within our system, with ACD locks used at site 1 and heparin locks at site 2. We assessed catheters for catheter dysfunction and infection. Both nontunneled dialysis catheters (NTDC) and tunneled dialysis catheters (TDC) were evaluated. We studied 250 catheters and 139 met inclusion criteria: 90 catheters in the ACD group and 49 in the heparin group. ACD had superior outcomes for NTDC; event rate was 0.052 for NTDC/ACD and 0.125 for NTDC/heparin (p = 0.032). There was no difference for TDC. Univariate (odds ratio [OR]: 1.88, confidence interval [CI]: 0.931, 3.82) and multivariate (OR: 1.35, CI: 0.64, 2.87) analyses demonstrated a trend toward increased odds of event with heparin. Catheter lock with 2.2% ACD has lower risk of catheter dysfunction as compared with that of 5000 U/ml heparin in the short term inpatient setting in NTDC and similar risk in TDC. PMID- 22074232 TI - Self-monitoring as a moderator between descriptive norms and drinking: findings among Korean and American university students. AB - Guided by the theory of normative social behavior (TNSB), this research examined whether a self-monitoring individual difference variable moderates the link between descriptive norms and drinking as well as drinking intentions such that the relations become stronger as self-monitoring becomes stronger. Contrary to our prediction, Study 1 showed that low self-monitoring Korean undergraduates were more likely to be guided by normative information when drinking and intending to drink when compared to those with high self-monitors. Study 2 was conducted using an American university sample, and results of the second study were identical to those of the first study. The relationship between descriptive norms and drinking was stronger among university students who are low self monitors as compared to those who are high self-monitors. Implications for interventions are discussed. PMID- 22074233 TI - Effectiveness of hospital-based decontamination during a simulated mass casualty exposure. PMID- 22074234 TI - Associations between seasonal variations in day length (photoperiod), sleep timing, sleep quality and mood: a comparison between Ghana (5 degrees ) and Norway (69 degrees ). AB - The hypothesis of whether day length (photoperiod) is an important zeitgeber (time-giver) for keeping the circadian rhythm entrained to a 24-hour cycle was examined, as was its association with sleep patterns and mood problems. Data were collected prospectively from a site with very large differences in daylight duration across seasons (Tromso in Norway, 69 degrees 39'N) and a site with very small seasonal differences in daylight duration (Ghana in Accra, 5 degrees 32'N). Two hundred subjects were recruited from both sites in January. At the follow-up in August, 180 and 150 subjects in Ghana and Norway participated, respectively. Use of a weekly sleep diary indicated low to moderately strong seasonal changes in rise- and bedtime, sleep efficiency and sleep onset latency only in the northern latitude. No seasonal changes in sleep duration or night awakenings were observed. The self-report measures indicated moderate to strong seasonal differences in insomnia and fatigue, and weaker differences in depressed mood in Norway, but small to non-existing seasonal differences in Ghana. Lack of daylight was related to phase-delayed rise- and bedtimes, increased problems falling asleep, daytime fatigue and depressive mood. However, total sleep duration and sleep quality appeared unaffected. PMID- 22074235 TI - An angel on my shoulder: a study of relationships between women with anorexia and healthcare professionals. AB - Adults with anorexia are an under-researched group because the usual focus is on adolescents. The relationships that occur between healthcare professionals and adults with anorexia are often challenging, because they do not necessarily agree on the goals of treatment. The therapeutic relationship is widely recognized as crucial to care, even healing and restorative in its own right but problematic in this setting. This is a phenomenological study of how therapeutic relationships are negotiated and maintained in a day care service. Six women with anorexia nervosa and seven of their healthcare professionals were interviewed in the care setting to explore their lived experience of their relationships. Six important themes emerged from the interviews: the authenticity of the relationship, safety, the externalization of the eating disorder, recovery measured in kilos, the power of hope and optimism and the use and acceptance of maternalism in the care setting. Findings suggest that patients appreciated the safety and security of care, but some were using the service as respite rather than recovery. Patients saw goals and tasks related directly to weight gain as irrelevant to their main concerns, but engagement with people who provided a secure, nurturing and maternalistic context for safety and optimism was seen as supportive. PMID- 22074236 TI - Microbial reduction of structural iron in interstratified illite-smectite minerals by a sulfate-reducing bacterium. AB - Clay minerals are ubiquitous in soils, sediments, and sedimentary rocks and could coexist with sulfate-reducing bacteria (SRB) in anoxic environments, however, the interactions of clay minerals and SRB are not well understood. The objective of this study was to understand the reduction rate and capacity of structural Fe(III) in dioctahedral clay minerals by a mesophilic SRB, Desulfovibrio vulgaris and the potential role in catalyzing smectite illitization. Bioreduction experiments were performed in batch systems, where four different clay minerals (nontronite NAu-2, mixed-layer illite-smectite RAr-1 and ISCz-1, and illite IMt 1) were exposed to D. vulgaris in a non-growth medium with and without anthraquinone-2,6-disulfonate (AQDS) and sulfate. Our results demonstrated that D. vulgaris was able to reduce structural Fe(III) in these clay minerals, and AQDS enhanced the reduction rate and extent. In the presence of AQDS, sulfate had little effect on Fe(III) bioreduction. In the absence of AQDS, sulfate increased the reduction rate and capacity, suggesting that sulfide produced during sulfate reduction reacted with the phyllosilicate Fe(III). The extent of bioreduction of structural Fe(III) in the clay minerals was positively correlated with the percentage of smectite and mineral surface area of these minerals. X-ray diffraction, and scanning and transmission electron microscopy results confirmed formation of illite after bioreduction. These data collectively showed that D. vulgaris could promote smectite illitization through reduction of structural Fe(III) in clay minerals. PMID- 22074237 TI - Active wound dressing with artificial capillaries for temporary wound irrigation and skin cell supply. AB - Medical treatment of burns and chronic wounds remains a challenge. We discussed a therapy concept that combines skin cell spray transplantation with a novel wound dressing based on artificial hollow fiber membrane capillaries. In skin cell based therapy development, autologous skin progenitor cells are isolated from a healthy skin area and sprayed onto the wound. A medical device was introduced that uses perfused capillaries, known from clinical plasma separation, as a temporarily applied extracorporeal wound capillary bed. The functions of the dressing are comparable with those of dialysis; the capillaries, however, are applied externally onto the wound. Perfusion with a clinical peripheral nutrition and buffer solution can provide wound irrigation, wound debris removal, cell nutrition, pH regulation, and electrolyte balance while potentially serving to address delivery of regenerative factors and antibiosis. An innovative active skin wound dressing that provides cell support and stimulates regeneration by wound irrigation is discussed. PMID- 22074239 TI - Effect of N(4)-phenyl substitution in 2-oxo-1,2-dihydroquinoline-3-carbaldehyde semicarbazones on the structure, DNA/protein interaction, and antioxidative and cytotoxic activity of Cu(II) complexes. AB - A new ligand, 2-oxo-1,2-dihydroquinoline-3-carbaldehyde semicarbazone (OQsc-H) (1);, its N(4)-phenyl derivative (OQsc-Ph) (2); and their corresponding copper(II) complexes [CuCl(2)(OQsc-H)].H(2)O.CH(3)OH (3), [CuCl(2)(OQsc Ph)(H(2)O)].CH(3)OH (4), and [CuNO(3)(OQsc-Ph)(H(2)O)]NO(3).H(2)O.C(2)H(5)OH (5) have been synthesized and characterized by structural, analytical, and spectral methods, in order to investigate the influence of N(4)-phenyl substitution on structure and pharmacological properties. In all of the complexes, the ligands coordinated to the Cu(II) ion in a neutral fashion via ONO donor atoms. The single-crystal X-ray structures of neutral complex (3) and cationic complex (5) exhibit a slightly distorted square-pyramidal structure, while neutral complex (4) revealed an octahedral structure. The interaction of the compounds with calf thymus DNA (CT-DNA) has been explored by absorption and emission titration methods, which revealed that compounds 1-5 could interact with CT-DNA through intercalation. A gel electrophoresis pictogram demonstrated the ability of the complexes (3-5) to cleave the pBR322 plasmid DNA through a hydrolytic process. The interactions of the compounds with bovine serum albumin (BSA) were also investigated using UV-visible, fluorescence, and synchronous fluorescence spectroscopic methods. The results indicated that all of the compounds could quench the intrinsic fluorescence of BSA in a static quenching process. Investigations of antioxidative properties showed that all of the compounds have strong radical scavenging potencies against hydroxyl radicals, 2,2-diphenyl-1 picrylhydrazyl radicals, nitric oxide, and superoxide anion radicals. Further, the cytotoxic effect of the compounds examined on cancerous cell lines such as human cervical cancer cells (HeLa), human laryngeal epithelial carcinoma cells (HEp-2), human liver carcinoma cells (Hep G2), human skin cancer cells (A431), and noncancerous NIH 3T3 mouse embryonic fibroblasts cell lines showed that all three complexes exhibited substantial cytotoxic activity. Further, all of the pharmacological investigations support the fact that there exists a strong influence of N(4)-phenyl substitution in semicarbazone. PMID- 22074240 TI - Structure and change in causes of death: An international summary. AB - Abstract Model patterns of the cause structure of mortality at different levels were established for males and females, based on data for 165 national populations. These patterns suggest that the cause of death most responsible for mortality variation is influenza/bronchitis, followed by 'other infectious and parasitic diseases', respiratory tuberculosis, and diarrhoeal disease. Together, these causes typically account for about 60 per cent of the change in level of mortality from all causes combined. Their respective contributions have not depended in an important way on the initial level of mortality. These results - especially tbe importance of the respiratory and diarrhoeal diseases - imply that past accounts may have over-emphasized the role in mortality decline of specific and well-defined infectious diseases and their corresponding methods of control. There is strong statistical support for the suggestion that most of the remainder of mortality variation should be ascribed to changes in cardio-vascular diseases, but that methods of cause-of-death assignment in high-mortality populations have often obscured the importance of these diseases. When death rates from 'other and unknown' causes are held constant, changes in cardio-vascular disease account for about one-quarter of the decline in mortality from 'all causes'.Although the causal factors are poorly established, corroborative results have been demonstrated cross-sectionally in the United States. The composition of the group of populations most deviant from the structural norms is apparently dominated by differentials in the mode of assigning deaths to cardio-vascular disease. However, when broad groups of regions or periods are distinguished, more subtle differences emerge. Controlling mortality level for all causes combined, diarrhoeal diseases are significantly higher in non-Western populations and southern/eastern Europe than in overseas Europe or northern/western Europe. These differences are probably related to standards of nutrition and personal hygiene, but may also reflect climatic factors. Much higher cardio-vascular mortality in overseas European populations than in non-Western populations at similar overall levels probably reflects variation in habits of life. Regional differences in death rates from violence, maternal mortality, respiratory tuberculosis and influenza/pneumonia/bronchitis are briefly noted and commented upon. Cause-of death structures at a particular level of mortality display some important changes over time. Respiratory tuberculosis and 'other infectious and parasitic diseases' have tended to contribute less and less to a certain level of mortality. They have in part been 'replaced' by diarrhoeal disease, specifically in non-Western populations. These developments reflect an accelerating rate of medical and public health progress against the specific infectious diseases, and a disappointing rate of progress against diarrhoeal disease. Western and non western populations have shared to approximately the same extent in the accelerating progress against infectious diseases, and developments during the post-war period are more appropriately viewed as an extension of prior trends rather than as radical departures therefrom. For males, cardio-vascular disease and cancer have significantly increased their contribution to a particular level of mortality, while no such tendency is apparent for females. These developments may be related to changes in personal behaviour and in environmental influences whose differential impact on the sexes has been demonstrated in epidemiological studies. Although we have avoided an explicit treatment of age by having recourse at the outset to standardization, certain of the results are apparently reflected in studies of age patterns of mortality. The joint occurrence in non-Western populations and Southern/Eastern populations of exceptionally high death rates from diarrhoeal disease may explain why the 'South' age-pattern, with it high death rates between ages one and five, is often the most accurate referent for use in Latin America and Asia. The fact that the list of populations with the least deviation cause structure is almost exclusively confined to members of the 'West' group of Coale and Demeny may account for the lack of persistent deviation in this group's age patterns. Finally, tbe increasing importance of cardio vascular disease and neoplasms in cause-of-death structures for males but not females is probably associated with the changing age patterns of male mortality noted by Coale and Demeny. PMID- 22074238 TI - Field and action potential recordings in heart slices: correlation with established in vitro and in vivo models. AB - BACKGROUND AND PURPOSE: Action potential (AP) recordings in ex vivo heart preparations constitute an important component of the preclinical cardiac safety assessment according to the ICH S7B guideline. Most AP measurement models are sensitive, predictive and informative but suffer from a low throughput. Here, effects of selected anti-arrhythmics (flecainide, quinidine, atenolol, sotalol, dofetilide, nifedipine, verapamil) on field/action potentials (FP/AP) of guinea pig and rabbit ventricular slices are presented and compared with data from established in vitro and in vivo models. EXPERIMENTAL APPROACH: Data from measurements of membrane currents (hERG, I(Na) ), AP/FP (guinea pig and rabbit ventricular slices), AP (rabbit Purkinje fibre), haemodynamic/ECG parameters (conscious, telemetered dog) were collected, compared and correlated to complementary published data (focused literature search). KEY RESULTS: The selected anti-arrhythmics, flecainide, quinidine, atenolol, sotalol, dofetilide, nifedipine and verapamil, influenced the shape of AP/FP of guinea pig and rabbit ventricular slices in a manner similar to that observed for rabbit PF. The findings obtained from slice preparations are in line with measurements of membrane currents in vitro, papillary muscle AP in vitro and haemodynamic/ECG parameters from conscious dogs in vivo, and were also corroborated by published data. CONCLUSION AND IMPLICATIONS: FP and AP recordings from heart slices correlated well with established in vitro and in vivo models in terms of pharmacology and predictability. Heart slice preparations yield similar results as papillary muscle but offer enhanced throughput for mechanistic investigations and may substantially reduce the use of laboratory animals. PMID- 22074241 TI - On the tempo of childbearing in England and Wales. AB - Abstract The paper describes a computerized model developed to simulate the fertility of a hypothetical marriage cohort in a closed population. The model was applied to England and Wales fertility data of marriage cohorts of the years 1951 to 1970. For each of these cohorts, the computer was programmed to construct five series of tables showing birth-order probabilities, family size frequency distribution, mean length of intervals between marriage and successive births, parity progression ratios and mean family sizes of fertile women. The results showed that the fertility of the cohorts of women who married between the middle 1950s and the early 1960s was character ized by a declining trend in the frequency of childlessness and by a dramatic increase in the proportion of marriages with two or more children. Since 1964 or so, there has been a downward trend in duration-specific birth-order probabilities. The analysis suggests that the recent drop in fertility may well prove to be the effect of an upward shift in the timing of births as well as a fall in completed fertility. PMID- 22074242 TI - Cost versus effectiveness of different birth control methods. AB - Abstract This paper is an empirical investigation of the mix of birth control methods that would be, allocationally efficient in a real population. Current British resource cost and effectiveness data for each method are presented in order to test the prevalent opinion that expenditure on abortion is allocationally inefficient. Even when abortion resources are valued to give a conservatively high cost, however, this opinion is not upheld. When both quantifiable resource costs and effectiveness are plotted for each method, some linear combination of coitus interruptus, and coitus interruptus with all failures terminated by abortion is shown to be the allocationally efficient frontier. PMID- 22074243 TI - The island-wide family planning programme in Taiwan: Analysis of the accomplishments of the past eight years. AB - Abstract Taiwan's island-wide family planning programme is the showcase of similar programmes in the developing world. In the past eight years, between 1964 and 1971, a cumulative total of 935,000 married women accepted the Lippes loop, 236,000 accepted the pill, and 116,000 couples accepted condoms. The prevalence rates of loop and pill users at the end of 1971 are estimated at 18.7 per cent and 3-6 per cent respectively. The programme had been recruiting more younger women of lower parity to practise family planning which is desirable, but a fact of concern is that a large proportion of the acceptors had had at least one son, and had accepted the methods to stop, rather than to space births. The 'life expectancy' of loop and pill, the two major contraceptives recommended in the programme, have been shorter than expected, 31.4 months without and 49.9 months with re-insertion for the loop, and only 10.5 months without re-taking for the pill. The concepts of 'half-life (retention)' and 'half-life (impact)', developed by the author, were applied in the analysis to obtain the values of 18.6 months and 25.7 months respectively for the loop, and 5.8 months and 9.2 months respectively for the pill all for the first segment. Only nine per cent of the total current loop wearers were aged 40-44 in 1964, but the proportion had increased substantially, to 20.5 per cent, in 1971. This 'ageing' of current users tends to minimize the demographic impact of the programme which is a factor of concern. Methods to overcome this and other problems should be explored for the final success of the programme. PMID- 22074244 TI - Residency differentials in Mormon fertility. AB - Abstract Although one of the most consistent findings of recent fertility studies is the convergence of the religious differentials in fertility, few data have been analysed to discover Mormon fertility trends and differentials. This paper, based on data obtained on 1,001 Mormon couples, is concerned with describing the effects that the dispersion of Mormon families from the Mormon centre in Utah to surrounding areas with various social conditions is having on the fertility of the re-located Mormon families. Data presented clearly show that such families do, on the average, have a lower fertility than do their Mormon contemporaries residing in the homogeneous Mormon society in Utah. They probably compromise their religious obligations to have children with the contradicting demands of their new environment. Their loyalty to these religious beliefs, however, is confirmed by data which show that they tend to have larger families in their new environments than do their non-Mormon neighbours. PMID- 22074245 TI - A note on cost-return calculations and decisions to migrate. AB - Abstract In the notions of the aggregative cost-benefit migration models, this paper questions the assumption that prospective migrants behave as if they are not only concerned with, but are able to calculate expected pecuniary and non pecuniary returns to re-location. Results of a survey which evaluates the role of cost-return calculations in decisions to migrate suggest that there may be population sub-groups who either do not care to make cost-returns calculations to migration, or who are unable to do so. PMID- 22074248 TI - Hesperetin-7,3'-O-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio. AB - BACKGROUND: Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4). While hesperetin-7,3'-O-dimethylether (HDME) is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs) in vitro, and its effects on ovalbumin-induced airway hyperresponsiveness in vivo, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD). METHODS: PDE1~5 activities were measured using a two step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [3H]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th)1/Th2 cytokine CBA kits, and total immunoglobulin (Ig)E or IgG2a levels were done using ELISA method. Xylazine (10 mg/kg)/ketamine (70 mg/kg)-induced anesthesia was performed. RESULTS: HDME revealed selective phosphodiesterase 4 (PDE4) inhibition with a therapeutic (PDE4H/PDE4L) ratio of 35.5 in vitro. In vivo, HDME (3~30 MUmol/kg, orally (p.o.)) dose-dependently and significantly attenuated the airway resistance (RL) and increased lung dynamic compliance (Cdyn), and decreased enhanced pause (Penh) values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-gamma, and tumor necrosis factor-alpha in bronchoalveolar lavage fluid (BALF) of these mice. In addition, HDME (3~30 MUmol/kg, p.o.) dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (Ig)E levels in the BALF and serum, and enhanced IgG2a level in the serum of these mice. CONCLUSIONS: HDME exerted anti-inflammatory effects, including suppression of AHR, and reduced expressions of inflammatory cells and cytokines in this murine model, which appears to be suitable for studying the effects of drugs on atypical asthma and COPD, and for screening those on typical asthma. However, HDME did not influnce xylazine/ketamine-induced anesthesia. Thus HDME may have the potential for use in treating typical and atypical asthma, and COPD. PMID- 22074249 TI - Peptide-directed HPMA copolymer-doxorubicin conjugates as targeted therapeutics for colorectal cancer. AB - Synthetic oligopeptides have emerged as a promising class of targeting ligands, providing a variety of choices for the construction of conjugates for desired ligand functionality. To explore the potential of short peptides as ligands for targeted delivery of macromolecular therapeutics for colorectal cancer (CRC), fluorescently labelled HPMA copolymers--bearing either G3-C12 or GE11 for targeting galectin-3 and epidermal growth factor receptor (EGFR), respectively- were synthesised and the mechanisms of their internalisation and subcellular fate in CRC cells were studied. The targetability of the G3-C12 bearing copolymers towards galectin-3 was further compared to that of galactose-containing copolymers. The resulting G3-C12-bearing conjugate actively and selectively targets CRC tumour cells over-expressing galectin-3 and exhibits superior targetability to galectin-3 when compared to the galactose-bearing copolymer. GE11 copolymer conjugate binds specifically and efficiently to EGFR over expressing cells, thus mediating internalisation to a significantly higher extent relative the copolymer conjugated to a scrambled sequence peptide. We further incorporated doxorubicin (DOX) into GE11 bearing copolymer via an acid-labile hydrazone bond. The GE11-DOX copolymer conjugate demonstrated higher cytotoxicity toward EGFR over-expressing cells relative to the control non-targeted DOX conjugate. Altogether, our results show a proof of principle for the selective delivery of DOX to the target CRC cells. PMID- 22074250 TI - State of malaria diagnostic testing at clinical laboratories in the United States, 2010: a nationwide survey. AB - BACKGROUND: The diagnosis of malaria can be difficult in non-endemic areas, such as the United States, and delays in diagnosis and errors in treatment occur too often. METHODS: A nationwide survey of laboratories in the United States and its nine dependent territories was conducted in 2010 to determine factors that may contribute to shortcomings in the diagnosis of malaria. This survey explored the availability of malaria diagnostic tests, techniques used, and reporting practices. RESULTS: The survey was completed by 201 participants. Ninety percent reported that their laboratories had at least one type of malaria diagnostic test available on-site. Nearly all of the respondents' laboratories performed thick and thin smears on-site; approximately 50% had access to molecular testing; and only 17% had access to rapid diagnostic tests on-site. Seventy-three percent reported fewer than five confirmed cases of malaria in their laboratory during the 12-month period preceding the survey. Twenty-eight percent stated that results of species identification took more than 24 hours to report. Only five of 149 respondents that performed testing 24 hours a day, 7 days a week complied with all of the Clinical and Laboratory Standards Institute (CLSI) guidelines for analysis and reporting of results. CONCLUSION: Although malaria diagnostic testing services were available to a majority of U.S. laboratories surveyed, very few were in complete compliance with all of the CLSI guidelines for analysis and reporting of results, and most respondents reported very few cases of malaria annually. Laboratories' difficulty in adhering to the rigorous CLSI guidelines and their personnel's lack of practice and proficiency may account for delays and errors in diagnosis. It is recommended that laboratories that infrequently process samples for malaria seek opportunities for practice and proficiency training annually and take advantage of available resources to assist in species identification. PMID- 22074251 TI - Influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in childhood acute lymphoblastic leukemia. AB - The prediction of high-dose methotrexate (HD-MTX) toxicity is a key issue in the individualization of treatment in childhood acute lymphoblastic leukemia (ALL). Our aim was to evaluate the influence of MTX pathway polymorphisms on HD-MTX treatment outcome in children with ALL. In total, 167 children with ALL were genotyped for methylenetetrahydrofolate dehydrogenase (MTHFD1) 1958G > A, methylenetetrahydrofolate reductase (MTHFR) 677C > T and 1298A > C and thymidylate synthase (TYMS) 2R > 3R polymorphisms. The MTHFD1 1958A allele significantly reduced the odds of hepatotoxicity (adjusted p = 0.009), while the TYMS 3R allele significantly reduced the odds of leukocytopenia and thrombocytopenia (adjusted p = 0.005 and adjusted p = 0.002, respectively). MTHFR polymorphisms did not influence HD-MTX-related toxicity, but a significant effect of MTHFR 677C > T-TYMS 2R > 3R and MTHFD1 1958G > A-MTHFR 677C > T interactions on HD-MTX-related toxicity was observed. None of the investigated polymorphisms influenced survival. Our study suggests an important role of polymorphisms and gene-gene interactions within the folate pathway in HD-MTX-related toxicity in childhood ALL. PMID- 22074252 TI - Room-temperature dissociation of 1,2-dibromodisilenes to bromosilylenes. AB - A room-temperature dynamic equilibrium between dibromodisilenes and bromosilylenes has been demonstrated by taking advantage of the steric protection using the fused-ring bulky 1,1,3,3,5,5,7,7-octa-R-s-hydrindacen-4-yl (Rind) groups. Although the bromosilylenes cannot be directly observed by spectroscopic methods, the thermal homolytic cleavage of the Si?Si double bond has been confirmed by a pseudo-first-order kinetics for the trapping with bis(trimethylsilyl)acetylene and a crossover reaction using two kinds of Rind substituted dibromodisilenes. The addition of 4-pyrrolidinopyridine (PPy) to the dibromodisilene leads to an equilibrium mixture between the dibromodisilene and a PPy adduct of bromosilylene, the latter being isolated and characterized. The substitution of the bromine atom in the dibromodisilene by the Grignard reagent is significantly accelerated by the addition of PPy. PMID- 22074253 TI - A practical look at the chemistry and biology of hydrogen sulfide. AB - SIGNIFICANCE: Hydrogen sulfide (H(2)S) is garnering increasing interest as a biologically relevant signaling molecule. The effects of H(2)S have now been observed in virtually every organ system and numerous physiological processes. RECENT ADVANCES: These studies have not only opened a new field of "gasotransmitter" biology, they have also led to the development of synthetic H(2)S "donating" compounds with the potential to be parlayed into a variety of therapeutic applications. CRITICAL ISSUES: Often lost in the exuberance of this new field is a critical examination or understanding of practical aspects of H(2)S chemistry and biology. This is especially notable in the areas of handling and measuring H(2)S, evaluating biosynthetic and metabolic pathways, and separating physiological from pharmacological responses. FUTURE DIRECTIONS: This brief review describes some of the pitfalls in H(2)S chemistry and biology that can lead or have already led to misleading or erroneous conclusions. The intent is to allow individuals entering or already in this burgeoning field to critically analyze the literature and to assist them in the design of future experiments. PMID- 22074256 TI - Surface enhanced coherent anti-stokes Raman scattering on nanostructured gold surfaces. AB - Coherent anti-Stokes Raman spectroscopy (CARS) is a well-known tool in multiphoton imaging and nonlinear spectroscopy. In this work we combine CARS with plasmonic surface enhancement on reproducible nanostructured surfaces. We demonstrate strong correlation between plasmon resonances and surface-enhanced CARS (SECARS) intensities on our nanostructured surfaces and show that an enhancement of ~10(5) can be obtained over standard CARS. Furthermore, we find SECARS to be >10(3) times more sensitive than surface-enhanced Raman Spectroscopy (SERS). We also demonstrate SECARS imaging of molecular monolayers. Our work paves the way for reliable single molecule Raman spectroscopy and fast molecular imaging on plasmonic surfaces. PMID- 22074255 TI - Molecular musings in microbial ecology and evolution. AB - A few major discoveries have influenced how ecologists and evolutionists study microbes. Here, in the format of an interview, we answer questions that directly relate to how these discoveries are perceived in these two branches of microbiology, and how they have impacted on both scientific thinking and methodology.The first question is "What has been the influence of the 'Universal Tree of Life' based on molecular markers?" For evolutionists, the tree was a tool to understand the past of known (cultured) organisms, mapping the invention of various physiologies on the evolutionary history of microbes. For ecologists the tree was a guide to discover the current diversity of unknown (uncultured) organisms, without much knowledge of their physiology.The second question we ask is "What was the impact of discovering frequent lateral gene transfer among microbes?" In evolutionary microbiology, frequent lateral gene transfer (LGT) made a simple description of relationships between organisms impossible, and for microbial ecologists, functions could not be easily linked to specific genotypes. Both fields initially resisted LGT, but methods or topics of inquiry were eventually changed in one to incorporate LGT in its theoretical models (evolution) and in the other to achieve its goals despite that phenomenon (ecology).The third and last question we ask is "What are the implications of the unexpected extent of diversity?" The variation in the extent of diversity between organisms invalidated the universality of species definitions based on molecular criteria, a major obstacle to the adaptation of models developed for the study of macroscopic eukaryotes to evolutionary microbiology. This issue has not overtly affected microbial ecology, as it had already abandoned species in favor of the more flexible operational taxonomic units. This field is nonetheless moving away from traditional methods to measure diversity, as they do not provide enough resolution to uncover what lies below the species level.The answers of the evolutionary microbiologist and microbial ecologist to these three questions illustrate differences in their theoretical frameworks. These differences mean that both fields can react quite distinctly to the same discovery, incorporating it with more or less difficulty in their scientific practice. PMID- 22074259 TI - Identification of gunshot residues in fabric targets using sector field inductively coupled plasma mass spectrometry technique and ternary graphs. AB - During criminal investigations involving firearms, the detection of gunshot residues (GSRs) is one of the most important evidences. In the present study, a new method to identify trace evidences of GSRs, deposited around the bullet entrance hole, in different types of fabrics used as targets, is described. The experiments were carried out using a 0.38-inch caliber revolver, and 9-mm and 0.40-inch caliber pistols. Testimonies of 2.25 cm(2) of the fabrics were cut around the bullet entrance and digested with 10% nitric acid. Antimony, barium, and lead were analyzed in the remaining solution using a sector field inductively coupled plasma mass spectrometer. The concentrations of the elements were detected at levels up to few microgram per square centimeter. The use of ternary graphics allowed us to identify specific patterns of distribution for blank samples and the clear distinction between the revolver and pistols used. PMID- 22074258 TI - Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis. AB - BACKGROUND: Psychostimulants and non stimulants are effective in the treatment of ADHD. Efficacy of both methylphenidate and atomoxetine has been established in placebo controlled trials. Direct comparison of efficacy is now possible due to availability of results from several head-to-head trials of these two medications. METHODS: All published, randomized, open label or double blind trials, comparing efficacy of methylphenidate with atomoxetine, in treatment of ADHD in children, diagnosed using DSM-IVTM criteria were included. The outcome studied was ADHDRS-IVParent:Inv score. The standardized mean difference (SMD) was used as a measure of effect size. RESULTS: Nine randomized trials comparing methylphenidate and atomoxetine, with a total of 2762 participants were included. Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine (SMD=0.09, 95% CI -0.08-0.26) (Z=1.06, p=0.29). Synthesis of data from eight trials found no significant difference in response rates (RR=0.93 95% CI 0.76-1.14, p=0.49). Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate (SMD=0.32, 95% CI 0.12-0.53 (Z=3.05, p<0.002). Immediate release methylphenidate was not superior to atomoxetine (SMD=-0.04, 95% CI -0.19-0.12) (Z=0.46, p=0.64). Excluding open label trials did not significantly alter the effect size (SMD=0.08, 95% CI -0.04 0.21) (Z=1.27, p=0.20). All-cause discontinuation was used as a measure of acceptability. There was no significant difference in all cause discontinuation between atomoxetine and methylphenidate (RR 1.22, 95% CI 0.87-1.71). There was significant heterogeneity among the studies (p=0.002, I2=67%). Subgroup analysis demonstrated the heterogeneity to be due to the open label trials (p=0.001, I2=81%). CONCLUSIONS: In general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents. However OROS methylphenidate is more effective than atomoxetine and may be considered as first line treatment in treatment of ADHD in children and adolescents. PMID- 22074257 TI - Prenylated acylphloroglucinols, chipericumins A-D, from Hypericum chinense. AB - Two new tetracyclic prenylated acylphloroglucinols, chipericumins A (1) and B (2), were isolated from the roots of Hypericum chinense, together with two new tricyclic prenylated acylphloroglucinols, chipericumins C (3) and D (4). Their structures were elucidated by spectroscopic data. Chipericumins A-D (1-4) are prenylated acylphloroglucinols having a spiro skeleton with an acyl group, a methyl group, a C(5) unit, and a monoterpene moiety in common. PMID- 22074260 TI - GTP-dependent RNA 3'-terminal phosphate cyclase from the hyperthermophilic archaeon Pyrococcus furiosus. AB - We discovered that the PF1549 gene in Pyrococcus furiosus encodes a very heat stable RNA 3'-terminal phosphate cyclase (Pf-Rtc). Although all previously reported Rtc proteins are ATP-dependent enzymes, we found that Pf-Rtc requires GTP for its cyclase activity at 95 degrees C. Low-level activation of the enzyme was also observed in the presence of dGTP but not other dNTPs, indicating that the guanine base is very important for Pf-Rtc activity. We analyzed a series of GTP analogues and found that the conversion from GTP to GMP is important for Pf Rtc activity and that an excess of GMP inhibits this activity. Gel-shift analysis clearly showed that the RNA-binding activity of Pf-Rtc is totally dependent on the linear form of the 3'-terminal phosphate, with an apparent K(d) value of 20 nm at 95 degrees C. Furthermore, we found that Pf-Rtc may contribute to GTP dependent RNA ligation activity through the PF0027 protein (a 2'-5' RNA ligase like protein in P. furiosus). The possible roles of Pf-Rtc and the importance of terminal phosphate structures in RNA are discussed. PMID- 22074261 TI - On your bike! a cross-sectional study of the individual, social and environmental correlates of cycling to school. AB - BACKGROUND: Active school transport (AST) has declined rapidly in recent decades. While many studies have examined walking, cycling to school has received very little attention. Correlates of cycling are likely to differ to those from walking and cycling enables AST from further distances. This study examined individual, social and environmental factors associated with cycling to school among elementary school-aged children, stratified by gender. METHODS: Children (n = 1197) attending 25 Australian primary schools located in high or low walkable neighborhoods, completed a one-week travel diary and a parent/child questionnaire on travel habits and attitudes. RESULTS: Overall, 31.2% of boys and 14.6% of girls cycled >= 1 trip/week, however 59.4% of boys and 36.7% of girls reported cycling as their preferred school transport mode. In boys (but not girls), school neighborhood design was significantly associated with cycling: i.e., boys attending schools in neighborhoods with high connectivity and low traffic were 5.58 times more likely to cycle (95% CI 1.11-27.96) and for each kilometer boys lived from school the odds of cycling reduced by 0.70 (95% CI 0.63-0.99). Irrespective of gender, cycling to school was associated with parental confidence in their child's cycling ability (boys: OR 10.39; 95% CI 3.79-28.48; girls: OR 4.03; 95% CI 2.02-8.05), parental perceived convenience of driving (boys: OR 0.42; 95% CI 0.23-0.74; girls: OR 0.40; 95% CI 0.20-0.82); and child's preference to cycle (boys: OR 5.68; 95% CI 3.23-9.98; girls: OR 3.73; 95% CI 2.26-6.17). CONCLUSION: School proximity, street network connectivity and traffic exposure in school neighborhoods was associated with boys (but not girls) cycling to school. Irrespective of gender, parents need to be confident in their child's cycling ability and must prioritize cycling over driving. PMID- 22074262 TI - 'We are doing our best': African and African-Caribbean fatherhood, health and preventive primary care services, in England. AB - Recent policy pronouncements emphasise the importance of engaging fathers with preventive primary care services. However, in England, there is a paucity of literature which examines African and African-Caribbean fathers' experiences of service provision. This paper reports a study that investigated African and African-Caribbean fathers' beliefs about fatherhood, health and preventive primary care services, with the aim of addressing the deficit in the literature. Nine focus groups involving 46 African and African-Caribbean fathers, recruited using purposive sampling, were undertaken between October 2008-January 2009. Fatherhood was seen as a core aspect of the participants' identities. The fathers enacted these identities in a number of ways, such as caring for and protecting children, which were influenced by spirituality, relationships with women, paid work and racism. The fathers had concerns about their bodies, medical conditions, physical activity and forms of consumption. However, their primary focus was on maintaining and improving the well-being of their children. This resulted in them neglecting their own health needs as they had to meet the obligations of family life and paid work. The fathers reported limited contact with preventive primary care services and were unaware of their purpose, function and availability. They identified ethnicity as a positive asset, and felt their families and communities had particular strengths. However they acknowledged that structural constraints, including racism, influenced their perceptions of and access to local health services. The engagement of African and African-Caribbean fathers needs to be addressed more specifically in policy as part of a broader programme of action to tackle health inequalities. In addition, child health services could build on fathers' commitment to children's well-being through practice that addresses fathers' as well as mothers' needs in families. PMID- 22074265 TI - Deformation, longitudinal shortening, and accordion of an ion stent. PMID- 22074266 TI - Development of a sampling patch to measure dermal exposures to monomeric and polymeric 1,6-hexamethylene diisocyanate: a pilot study. AB - The purpose of this study was to develop and evaluate a patch sampler to monitor dermal exposures to monomeric and polymeric 1,6-hexamethylene diisocyanate (HDI) in the automotive refinishing industry. Different patch materials were used to construct the patches, and patches impregnated with a derivatizing solution were compared with those that were not impregnated. We observed that impregnated felt patches measured significantly more HDI monomer (p = 0.04) than non-impregnated patches in a controlled experiment. Both impregnated and non-impregnated patches were compared with the tape-strip method by monitoring three spray painters' dermal exposure to monomeric and polymeric HDI. Isocyanurate was the predominant species measured by all three sampler types with detectable levels in >86% of samples. Overall, tape-strips of exposed skin measured lower levels of monomeric and polymeric HDI than impregnated patch samplers at the same sampling site on the skin. Unlike tape-strips, impregnated patches are not as prone to evaporative or reactive losses or losses due to rapid penetration into the skin. Further investigations are warranted to evaluate these and other methods to measure dermal exposure to workers under occupational conditions to better understand the relationship between dermal exposure and internal dose. PMID- 22074267 TI - Bi2(IO4)(IO3)3: a new potential infrared nonlinear optical material containing [IO4](3-) anion. AB - A new potential infrared (IR) nonlinear optical (NLO) material Bi(2)(IO(4))(IO(3))(3) was synthesized by hydrothermal method. Bi(2)(IO(4))(IO(3))(3) crystallizes in the chiral orthorhombic space group P2(1)2(1)2(1) (No. 19) with a = 5.6831(11) A, b = 12.394(3) A, and c = 16.849(3) A. It exhibits a three-dimensional framework through a combination of the IO(3), IO(4), BiO(8), and BiO(9) polyhedra and is the first noncentrosymmetric (NCS) structure containing [IO4](3-) anion. Bi(2)(IO(4))(IO(3))(3) has an IR cutoff wavelength of 12.3 MUm and belongs to the type 1 phase-matchable class with a moderately large SHG response of 5 * KDP, which is in good agreement with the theoretical calculations. PMID- 22074268 TI - Co-morbid diabetes in patients with Crohn's disease predicts a greater need for surgical intervention. AB - BACKGROUND: The prevalence of diabetes is increasing rapidly. Given its pro inflammatory nature, comorbid diabetes may affect the course of Crohn's disease (CD). AIM: To determine whether comorbid diabetes influences the natural history of CD. METHODS: We compared a cohort with CD and comorbid diabetes to a nondiabetic control population and calculated the period prevalence of surgical intervention over a 5-year period. Unadjusted and adjusted odds-ratios were calculated regarding the need for surgical intervention using univariate and multivariate logistic regression. RESULTS: A total of 240 patients were identified, 16 of whom were diabetics (6.7%). The period prevalence of CD specific surgery in the diabetic cases was 75.0% and in the nondiabetic controls, 31.7%. The diabetic patients were more obese than the controls (44% vs. 10%; P < 0.0001) and older than the controls (47.4 years vs. 38.6; P < 0.01). There was no difference in the frequency of biologic therapy use, immunomodulator use, smoking, perianal disease, ileal involvement or corticosteroid use between the diabetics and controls. Univariate analysis revealed that diabetes (OR 6.46 [95% CI 2.01-20.8]), smoking (OR 2.46 [95% CI 1.24-4.90]), ileal disease (OR 2.21 [95% CI 1.15-4.24]) and obesity (OR 2.22 [95% CI 1.04-4.77]) were risk factors for needing surgery. After adjustment for covariates, the OR for surgical intervention in diabetics was 5.4 (95% CI 1.65-17.64). CONCLUSION: Co-morbid diabetes in patients with Crohn's disease predicts a greater need for surgical intervention. PMID- 22074271 TI - Comment on vertically fractured teeth without root canal fillings. PMID- 22074269 TI - Body electrical loss analysis (BELA) in the assessment of visceral fat: a demonstration. AB - BACKGROUND: Body electrical loss analysis (BELA) is a new non-invasive way to assess visceral fat depot size through the use of electromagnetism. BELA has worked well in phantom measurements, but the technology is not yet fully validated. METHODS: Ten volunteers (5 men and 5 women, age: 22-60 y, BMI: 21-30 kg/m(2), waist circumference: 73-108 cm) were measured with the BELA instrument and with cross-sectional magnetic resonance imaging (MRI) at the navel level, navel +5 cm and navel -5 cm. The BELA signal was compared with visceral and subcutaneous fat areas calculated from the MR images. RESULTS: The BELA signal did not correlate with subcutaneous fat area at any level, but correlated significantly with visceral fat area at the navel level and navel +5 cm. The correlation was best at level of navel +5 cm (R(2) = 0.74, P < 0.005, SEE = 29.7 cm(2), LOOCV = 40.1 cm(2)), where SEE is the standard error of the estimate and LOOCV is the root mean squared error of leave-one-out style cross-validation. The average estimate of repeatability of the BELA signal observed through the study was +/-9.6 %. One of the volunteers had an exceptionally large amount of visceral fat, which was underestimated by BELA. CONCLUSIONS: The correlation of the BELA signal with the visceral but not with the subcutaneous fat area as measured by MRI is promising. The lack of correlation with the subcutaneous fat suggests that subcutaneous fat has a minor influence to the BELA signal. Further research will show if it is possible to develop a reliable low-cost method for the assessment of visceral fat either using BELA only or combining it, for example, with bioelectrical impedance measurement. The combination of these measurements may help assessing visceral fat in a large scale of body composition. Before large scale clinical testing and ROC analysis, the initial BELA instrumentation requires improvements. The accuracy of the present equipment is not sufficient for such new technology. PMID- 22074272 TI - Does mineral trioxide aggregate reinforce the immature roots? PMID- 22074273 TI - Does MTA really increase expression of tissue inhibitor of metalloproteinase (TIMP-2) in extracted teeth? PMID- 22074274 TI - Inotropes and vasopressors: more than haemodynamics! AB - Circulatory shock is characterized by arterial hypotension requiring fluid resuscitation combined with inotropes and/or vasopressors to correct the otherwise life-threatening impairment of oxygen supply to peripheral tissues. Catecholamines represent the current therapeutic choice, but this standard is only based on empirical clinical experience. Although there is evidence that some catecholamines may be better than others, it is a matter of debate which one may be the most effective and/or the safest for the different situations. In their review in this issue of the British Journal of Pharmacology, Bangash et al. provide an overview of the pharmacology as well as the available clinical data on the therapeutic use of endogenous catecholamines, their synthetic derivatives and a range of other agents (vasopressin and its analogues, PDE inhibitors and levosimendan). The authors point out that, despite well-established receptor pharmacology, the clinical effects of these treatments are poorly understood. Hence, further investigations are essential to determine which catecholamine, or, in a broader sense, which alternative vasopressor and/or inotrope is the most appropriate for a particular clinical condition. PMID- 22074275 TI - Integrated biomarker discovery: combining heterogeneous data. PMID- 22074276 TI - Artificial microorgans: a microfluidic tool for in vitro assessment of toxicity. PMID- 22074278 TI - Laboratory and software applications for clinical trials: the global laboratory environment. AB - The Applied Pharmaceutical Software Meeting is held annually. It is sponsored by The Boston Society, a not-for-profit organization that coordinates a series of meetings within the global pharmaceutical industry. The meeting generally focuses on laboratory applications, but in recent years has expanded to include some software applications for clinical trials. The 2011 meeting emphasized the global laboratory environment. Global clinical trials generate massive amounts of data in many locations that must be centralized and processed for efficient analysis. Thus, the meeting had a strong focus on establishing networks and systems for dealing with the computer infrastructure to support such environments. In addition to the globally installed laboratory information management system, electronic laboratory notebook and other traditional laboratory applications, cloud computing is quickly becoming the answer to provide efficient, inexpensive options for managing the large volumes of data and computing power, and thus it served as a central theme for the meeting. PMID- 22074279 TI - The importance of HT-ADME in drug discovery. AB - The inaugural meeting of the Boston Society High-Throughput Absorption, Distribution, Metabolism and Excretion (HT-ADME) Conference was held in Cambridge, MA (USA). The theme was 'The Importance of HT-ADME in Drug Discovery' and the organizers of the conference stressed the importance of incorporating audience participation and discussion in the field. The conference hosted 65 attendees and 16 presentations, which was a good size to achieve the goal of active participation while maintaining focus on HT-ADME. The speakers provided broad coverage of HT-ADME within the drug discovery arena, while remembering that the overall goal in drug discovery is identifying potential drug candidates to move forward into development. PMID- 22074280 TI - Anticoagulant counter ion impact on bioanalytical LC-MS/MS assay performance: additional validation required? PMID- 22074281 TI - Anticoagulant counter ion impact on bioanalytical LC-MS/MS assays: results from discussions and experiments within the European Bioanalysis Forum. AB - BACKGROUND: In regulated bioanalysis, the need for partial validation when changing the counter ion of the anticoagulant is currently being debated within the bioanalytical community. To date, industry and the health authorities have not yet reached a consensus on this issue. The aim of the present study was to evaluate the impact of a change in counter ion when using the same anticoagulant on LC-MS/MS assay performance for a broad array of new chemical entities, compiling data generated at companies within the European Bioanalysis Forum (EBF). RESULTS: In all, 15 EBF member companies provided experimental data on partial validation. In total, data from 42 LC-MS/MS assays were evaluated. The results show that a change in counter ion when using the same anticoagulant had no impact on assay performance. CONCLUSION: Based on these results and on conclusions from previous studies, the EBF recommends that in regulated bioanalysis, plasma samples containing different counter ions, but the same anticoagulant, should be regarded as equal matrices, thus removing any need for partial validation. PMID- 22074282 TI - Platform for analysis of anthranilic acid N-glycan derivatives utilizing multipolarity mode LC-MS with hydrophilic interaction chromatography separation and ion trap MS/MS. AB - BACKGROUND: The structure of glycans is complex compared with linear polymers such as proteins and nucleic acids. Structural assignment of these compounds is particularly challenging to the bioanalyst. Here we present a multipolarity mode LC-MS platform for analysis of anthranilic acid-derivatized N-glycans. RESULTS: Multipolarity mode LC-MS analysis of N-glycan anthranilic aid (2AA) derivatives, collected under conditions that stabilize sialyloligosaccharides, provided more complete structural coverage than either mode when used alone. Structural assignment was simplified by the use of 2AA, which localizes charge to the reducing end in both modes facilitating the production of reducing end fragment dominant spectra. CONCLUSION: Multimode analysis of high-mannose, hybrid and complex N-glycans, under conditions used in this method, is superior to either mode when used alone. PMID- 22074283 TI - Iontophoresis of a 13 kDa protein monitored by subcutaneous microdialysis in vivo. AB - BACKGROUND: The purpose of this study was to optimize parameters pertaining to microdialysis technique so as to make this method feasible for evaluating transdermal transport of macromolecules. RESULTS: Microdialysis experiments were performed in vivo using hairless rats with daniplestim as the model protein. Two perfusion fluids - phosphate-buffered saline (PBS) and 3% dextran in PBS - were evaluated with respect to their effect on sample volume retrieval and recovery of the target protein from the microdialysis probe. Incorporation of dextran-60 in the perfusion fluid reduced fluid loss to 10% as opposed to 34% in the absence of dextran-60. Improvement in daniplestim recovery was also seen with dextran-PBS (56.5 +/- 10.3%) as the perfusion fluid than with PBS alone (26.7+/-4.5%). CONCLUSION: Subcutaneous levels of daniplestim were measured following iontophoresis after improving recovery and minimizing fluid loss from the microdialysis probe. PMID- 22074284 TI - MALDI imaging mass spectrometry: bridging biology and chemistry in drug development. AB - Our understanding of drug tissue distribution impacts a number of areas in drug development, including: pharmacology, pharmacokinetics, safety, drug-drug interactions, transport and metabolism. Despite their extensive use, autoradiography and tissue homogenate LC-MS analysis have limitations in providing a comprehensive assessment of tissue distributions. In the case of autoradiography, it is the inability to distinguish between parent drug and drug metabolites. In LC-MS analysis of tissue homogenate, all tissue localization information is lost. The emerging technique of MALDI imaging mass spectrometry has the capability to distinguish between parent and metabolites while maintaining spatial distribution in tissues. In this article, we will review the MALDI imaging MS methodology as applied to drug development and provide examples highlighting the impact of this important technique in drug development. PMID- 22074285 TI - Exploring the metabolic state of microorganisms using metabolomics. AB - Microorganisms depend on their ability to modulate their metabolic composition according to specific circumstances, such as different phases of the growth cycle and circadian rhythms, fluctuations in environmental conditions, as well as experimental perturbations. A thorough understanding of these metabolic adaptations requires the ability to comprehensively identify and quantify the metabolome of bacterial cells in different states. In this review, we present an overview of the diverse metabolomics approaches recently adopted to explore the metabolism of a wide variety of microorganisms. Focusing on a selection of illustrative case studies, we assess the different experimental designs used and explore the major achievements and remaining challenges in the field. We conclude by discussing the important complementary information provided by computational methods such as genome-scale metabolic modeling, which enable an integrated analysis of metabolic state changes in the context of overall cellular physiology. PMID- 22074286 TI - Absolute quantitation of protein therapeutics in biological matrices by enzymatic digestion and LC-MS. AB - The advancement of biotechnology has led to an increase in biotherapeutic drugs, especially recombinant proteins and monoclonal antibodies. Ligand-binding assays or immunoassays are the standard methods of choice in pharmacokinetic studies in support of drug discovery and development for protein therapeutics. LC-MS-based methodologies are increasingly used as alternatives to immunoassays for absolute protein quantitation in biological samples. We review recent advancements in absolute quantitation of protein therapeutics in biological matrices by enzymatic digestion and LC-MS. PMID- 22074288 TI - Genetic diversity and genotype multiplicity of Plasmodium falciparum infections in symptomatic individuals in the maritime region of Togo. AB - OBJECTIVE: To assess the genotype prevalence and the multiplicity of Plasmodium falciparum infections in the maritime region of Togo. METHODS: We enrolled 309 symptomatic individuals aged from 6 months to 15 years from Be/Lome and Tsevie, two malaria endemic zones. The number and the proportions of merozoite surface proteins 1, 2 and 3 genotypes in patients were determined using capillary electrophoresis genotyping. We further investigated the possible association between transaminases and homocysteine, and the severity of the disease. RESULTS: Of the 309 samples genotyped, 210 tested positive to msp-1, 227 to msp-2 and 193 to msp-3. The nested PCR revealed 22 different alleles for the allelic family msp 1, 33 for msp-2 and 13 for msp-3. At each locus, the family distribution was 54.58% of K1, 25% of MAD20 and 20.42% of RO33 for msp-1, and 51.71% and 48.29% of FC27 and 3D7, respectively, for msp-2. For all these allelic variants, the distribution was associated with neither the severity of malaria nor the zone of habitation. Pearson correlation coefficients between either the levels of homocysteine or the transaminase and the severity of the disease were very low. CONCLUSION: The severity of malaria was not associated with higher multiplicity of infections and did not appear restricted to particular genotypes. More comprehensive explorations including immunity, genetic factors, nutritional and sociologic status of the population could clarify the situation. PMID- 22074289 TI - Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients. AB - BACKGROUND: Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients. METHODS: We studied 48 patients (16F; age 68 yrs +/- 8; BMI 26 +/- 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (DeltaO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation. RESULTS: Patients with a peak exercise EELV (%TLC) >= 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with DeltaO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, DeltaO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value >= 75% as a threshold value, were <= 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and <= 10,000 Hg . bpm (0.720 sensitivity and 0.783 specificity), respectively. CONCLUSION: The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function. PMID- 22074290 TI - Synthesis of dragmacidin D via direct C-H couplings. AB - Dragmacidin D, an emerging biologically active marine natural product, has attracted attention as a lead compound for treating Parkinson's and Alzheimer's diseases. Prominent structural features of this compound are the two indole pyrazinone bonds and the presence of a polar aminoimidazole unit. We have established a concise total synthesis of dragmacidin D using direct C-H coupling reactions. Methodological developments include (i) Pd-catalyzed thiophene-indole C-H/C-I coupling, (ii) Pd-catalyzed indole-pyrazine N-oxide C-H/C-H coupling, and (iii) acid-catalyzed indole-pyrazinone C-H/C-H coupling. These regioselective catalytic C-H couplings enabled us to rapidly assemble simple building blocks to construct the core structure of dragmacidin D in a step-economical fashion. PMID- 22074291 TI - Pilose antler polypeptides promote chondrocyte proliferation via the tyrosine kinase signaling pathway. AB - BACKGROUND: Pilose antler polypeptides (PAP) have been reported to promote chondrocyte proliferation. However, the underlying mechanism remains unclear. The present study was to investigate the effects of PAP on the proliferation of chondrocytes and its underlying mechanism. METHODS: Chondrocytes isolated from the knee of Zealand white rabbits were cultured. The second generation chondrocytes were collected and identified using safranin-O staining. The chondrocytes were divided into the following 4 groups including serum-free, PAP, genistein (an inhibitor of tyrosine kinases), and PAP plus genistein group. Cell viability was analyzed using the MTT assay. The cell cycle distribution of the chondrocytes was analyzed by flow cytometry. The expression levels of cyclin A was detected using immunocytochemical staining. RESULTS: No significant difference was observed between serum-free and genistein group. Treatment of the cultures with PAP produced a significant dose-dependent increase in cell viability, the percentage proportion of chondrocytes in the S phase and Cyclin A expression as well. However, the promoting effect of PAP on chondrocyte proliferation were dose-dependently inhibited by genistein, whereas genistein alone had no effect on proliferation of isolated chondrocytes. CONCLUSIONS: The data demonstrate that PAP promotes chondrocyte proliferation with the increased cell number, percentage proportion of chondrocytes in S phase and expression of protein cyclin A via the TK signaling pathway. PMID- 22074292 TI - Accelerated high-resolution differential ion mobility separations using hydrogen. AB - The resolving power of differential ion mobility spectrometry (FAIMS) was dramatically increased recently by carrier gases comprising up to 75% He or various vapors, enabling many new applications. However, the need for resolution of complex mixtures is virtually open-ended and many topical analyses demand yet finer separations. Also, the resolving power gains are often at the expense of speed, in particular making high-resolution FAIMS poorly compatible with online liquid-phase separations. Here, we report FAIMS employing hydrogen, specifically in mixtures with N(2) containing up to 90% H(2). Such compositions raise the mobilities of all ions and thus the resolving power beyond that previously feasible, while avoiding the electrical breakdown inevitable in He-rich mixtures. The increases in resolving power and ensuing peak resolution are especially significant at H(2) fractions above ~50%. Higher resolution can be exchanged for acceleration of the analyses by up to ~4 times. For more mobile species such as multiply charged peptides, this exchange is presently forced by the constraints of existing FAIMS devices, but future designs optimized for H(2) should consistently improve resolution for all analytes. PMID- 22074293 TI - Correlates of time spent walking and cycling to and from work: baseline results from the commuting and health in Cambridge study. AB - PURPOSE: Environmental perceptions and psychological measures appear to be associated with walking and cycling behaviour; however, their influence is still unclear. We assessed these associations using baseline data from a quasi experimental cohort study of the effects of major transport infrastructural developments in Cambridge, UK. METHODS: Postal surveys were sent to adults who travel to work in Cambridge (n = 1582). Questions asked about travel modes and time spent travelling to and from work in the last week, perceptions of the route, psychological measures regarding car use and socio-demographic characteristics. Participants were classified into one of two categories according to time spent walking for commuting ('no walking' or 'some walking') and one of three categories for cycling ('no cycling', '1-149 min/wk' and ' >= 150 min/wk'). RESULTS: Of the 1164 respondents (68% female, mean (SD) age: 42.3 (11.4) years) 30% reported any walking and 53% reported any cycling to or from work. In multiple regression models, short distance to work and not having access to a car showed strong positive associations with both walking and cycling. Furthermore, those who reported that it was pleasant to walk were more likely to walk to or from work (OR = 4.18, 95% CI 3.02 to 5.78) and those who reported that it was convenient to cycle on the route between home and work were more likely to do so (1-149 min/wk: OR = 4.60, 95% CI 2.88 to 7.34; >= 150 min/wk: OR = 3.14, 95% CI 2.11 to 4.66). Positive attitudes in favour of car use were positively associated with time spent walking to or from work but negatively associated with cycling to or from work. Strong perceived behavioural control for car use was negatively associated with walking. CONCLUSIONS: In this relatively affluent sample of commuters, a range of individual and household characteristics, perceptions of the route environment and psychological measures relating to car use were associated with walking or cycling to and from work. Taken together, these findings suggest that social and physical contexts of travel decision making should be considered and that a range of influences may require to be addressed to bring about behaviour change. PMID- 22074294 TI - Thymosin beta4: a multi-functional regenerative peptide. Basic properties and clinical applications. AB - INTRODUCTION: Thymosin beta(4), a low molecular weight, naturally-occurring peptide plays a vital role in the repair and regeneration of injured cells and tissues. After injury, thymosin beta(4), is released by platelets, macrophages and many other cell types to protect cells and tissues from further damage and reduce apoptosis, inflammation and microbial growth. Thymosin beta(4) binds to actin and promotes cell migration, including the mobilization, migration, and differentiation of stem/progenitor cells, which form new blood vessels and regenerate the tissue. Thymosin beta(4) also decreases the number of myofibroblasts in wounds, resulting in decreased scar formation and fibrosis. AREAS COVERED: This article will cover the many thymosin beta(4) activities that directly affect the repair and regeneration cascade with emphasis on its therapeutic uses and potential. Our approach has been to evaluate the basic biology of the molecule as well as its potential for clinical applications in the skin, eye, heart and brain. EXPERT OPINION: The considerable advances in our understanding of the functional biology and mechanisms of action of thymosin beta(4) have provided the scientific foundation for ongoing and projected clinical trials in the treatment of dermal wounds, corneal injuries and in the regeneration and repair of heart and CNS tissue following ischemic insults and trauma. PMID- 22074295 TI - Psychosocial processes influencing weight management among persons newly prescribed atypical antipsychotic medications. AB - The purpose was to generate a theory of the psychosocial processes influencing weight management among persons newly prescribed atypical antipsychotic medications. A grounded theory research design was used to guide the study. Semi structured interviews were the method of data collection, and analysis was performed using constant comparison. Using theoretical sampling, a sample of 11 participants with first-episode psychosis prescribed atypical antipsychotics for at least 8 weeks, and five participants with a diagnosis of chronic schizophrenia prescribed atypical antipsychotic medication for at least 3 years were recruited from an outpatient psychiatric programme. Contextual factors influencing weight management were: accessibility to resources, unstructured lifestyle, and others' perception of weight. Conditions influencing weight management were: rapid weight gain, insatiable hunger and lack of motivation boosters. Participants' early responses to weight gain included discontinuing medications, choosing lower calorie foods, using walking in daily activities as exercise, accepting weight gain and trying to manage weight but giving up. The consequences revealed from data analysis were contemplating weight management and not trying, as the barriers to weight management exceeded the facilitators. The theoretical framework developed in this study can assist with the understanding and management of weight gain among this unique population. PMID- 22074296 TI - Basal renal tubular epithelial cell vacuolization and alcoholic ketoacidosis. AB - Subnuclear renal tubular epithelial cell vacuolization is a marker for diabetic ketoacidosis. Whether it is because of hyperglycemia or of ketoacidosis is unclear. To examine the effect of ketoacidosis on renal cells in isolation, five cases of lethal alcoholic ketoacidosis without hyperglycemia were examined (vitreous humor beta-hydroxybutyrate: 6.42-8.75 mM, mean 7.66 mM; and glucose: 0.1-4.2 mM, mean 1.46 mM). Microscopic examination of the kidneys revealed basal vacuoles in three cases (60%). Seven control cases with acute alcohol toxicity without ketoacidosis (blood alcohol: 0.18-0.43%, mean 0.31%; and beta hydroxybutyrate: 0.12-0.42 mM, mean 0.21 mM) did not have these changes. In this study, basal epithelial vacuolization was found only in cases with significant ketoacidosis. Although the numbers are small, the finding of basal renal tubular epithelial vacuolization in normoglycemic cases with elevated beta hydroxybutyrate levels provide further evidence that disordered lipid metabolism may be involved in the pathogenesis of this phenomenon. PMID- 22074297 TI - Indirect evidence for microbiota reduction through dietary mannanoligosaccharides in the pigeon, an avian species without functional caeca. AB - A feeding trial was conducted to evaluate the effects of mannanoligosaccharides (MOS) on nutrient digestibility, intestinal pH, gut morphology and faecal bacteriology of pigeons, as model for birds without functional caeca. Sixteen adult pigeons (Columba livia domestica) were randomly allotted to either an extruded pellet diet with or without 0.4% MOS. After an adaptation period of 24 days, excreta were collected during 4 days. Apparent nutrient digestibility coefficients were determined using total collection method. Further, excreta pH was measured and percentage of uric acid determined. Fresh excreta were cultured for measurement of colony-forming units for Escherichia coli. At the end, the gastrointestinal tract (GIT) was excised and pH measurements performed on the separate GIT sections. Finally, pancreas, liver, gizzard and abdominal fat pad were weighed, and standardised segments of duodenum and jejunum were removed for microscopic measurement of crypt depth, villus height and muscularis thickness. Feed intake and water intake were similar between control diet and MOS diet. Intestinal pH was unaffected by MOS supplementation; however, excreta pH was significantly lower in pigeons on the MOS diet. Although nutrient digestibility was similar between treatments, uric acid content of excreta was significantly higher in the MOS group in relation to the control group. Further, duodenal crypt depth, villus height and muscularis thickness, as well as jejunal muscularis thickness were all significantly reduced by MOS supplementation. No effect of MOS supplementation was seen on the counts of E. coli. Furthermore, despite marked differences on both GIT morphology and uric acid content of excreta, apparent digestibility coefficients, and organ weights, were similar between treatments. It is suggested that the MOS-induced changes on gut morphology and the reduced excreta pH reflect a reduced bacterial challenge in the intestine of pigeons. Supplementation of MOS, therefore, has potential as prebiotic strategy in birds without functional caeca. PMID- 22074299 TI - Nursing theory and management. PMID- 22074298 TI - Inter-rater reliability of assessed prenatal maternal occupational exposures to solvents, polycyclic aromatic hydrocarbons, and heavy metals. AB - Because direct measurements of past occupational exposures are rarely available in population-based case-control studies, exposure assessment of job histories by multiple expert raters is frequently used; however, the subjective nature of this method makes measuring reliability an important quality control step. We evaluated inter-rater reliability of 7729 retrospective jobs reported in the National Birth Defects Prevention Study. Jobs were classified as exposed, unexposed, or exposure unknown by two independent industrial hygienists; exposed jobs were further evaluated for intensity, frequency, and routes. Exposure prevalence ranged from 0.1-9.8%. Inter-rater reliability for exposure (yes/no), assessed by kappa coefficients, was fair to good for cadmium (kappa = 0.46), chlorinated solvents (kappa = 0.59), cobalt (kappa = 0.54), glycol ethers (kappa = 0.50), nickel compounds (kappa = 0.65), oil mists (kappa = 0.63), and Stoddard Solvent (kappa = 0.55); PAHs (kappa = 0.24) and elemental nickel (kappa = 0.37) had poor agreement. After a consensus conference resolved disagreements, an additional 4962 jobs were evaluated. Inter-rater reliability improved or stayed the same for cadmium (kappa = 0.51), chlorinated solvents (kappa = 0.81), oil mists (kappa = 0.63), PAHs (kappa = 0.52), and Stoddard solvent (kappa = 0.92) in the second job set. Inter-rater reliability varied by exposure agent and prevalence, demonstrating the importance of measuring reliability in studies using a multiple expert rater method of exposure assessment. PMID- 22074300 TI - Theory-based practice in a major medical centre. AB - AIMS: This project was designed to improve care quality and nursing staff satisfaction. BACKGROUND: Nursing theory structures thought and action as demonstrated by evidence of improvement in complex health-care settings. Nursing administrators selected Modelling and Role-Modelling (MRM) for the theory-based practice goal in their strategic plan. METHODS: An action research approach structured implementation of MRM in a 1-year consultation project in 2001-2002. RESULTS: Quality of health care improved according to national quality assessment ratings, as well as patient satisfaction and nurse satisfaction. CONCLUSIONS: Modelling and Role-Modelling demonstrated capacity to structure nursing thought and action in patient care in a major medical centre. Uniformity of patient care language was valued by nurses as well as by allied health providers who wished to learn the holistic MRM style of practice. The processes of MRM and action research contributed to project success. IMPLICATIONS FOR NURSING MANAGEMENT: A positive health-care change project was carried out in a large medical centre with action research. Introducing MRM theory-based practice was a beneficial decision by nursing administration that improved care and nurse satisfaction. Attention to nursing practice stimulated career development among the nurses to pursue bachelors, masters, and doctoral degrees. PMID- 22074301 TI - An examination of the sustainable adoption of whole-person care (WPC). AB - AIM: This study illustrates how King's theory of goal attainment was used to focus an examination of whole-person care (WPC) and to extend the range of knowledge needed for WPC and nursing practice. BACKGROUND: Leadership implemented a faith-based innovation using continuing education for patient care that incorporates body-mind-spirit and eight principles called CREATION. Three questions arose: (1) Is there an evidence-based framework to determine whether the philosophy supports the discipline of nursing? (2) How extensive is the adoption and application of WPC? (3) Does the model make a difference in the context of nurse-patient interactions and outcomes in support of Magnet recognition criteria? METHODS: Interpretative phenomenology was used and an interview protocol was developed to examine the adoption and movement toward a culture of WPC. RESULTS: WPC was 'lived.' it is a relationship-oriented patient care model. However, except in direct patient care, the principles of creation were poorly diffused. IMPLICATIONS FOR NURSING MANAGEMENT: These results contribute to nursing leadership's roles in fostering a workplace climate that enables the diffusion of innovative models of care. In addition, these results support the Institute of Medicine's call for nurses to take the lead in adopting innovations and provides leaders with actionable strategies. PMID- 22074302 TI - Evaluating nurse staffing patterns and neonatal intensive care unit outcomes using Levine's Conservation Model of Nursing. AB - AIMS: To explore the influences of intensity of nursing care and consistency of nursing caregivers on health and economic outcomes using Levine's Conservation Model of Nursing as the guiding theoretical framework. BACKGROUND: Professional nursing practice models are increasingly being used although limited research is available regarding their efficacy. METHOD: A structural equation modelling approach tested the influence of intensity of nursing care (direct care by professional nurses and patient-nurse ratio) and consistency of nursing caregivers on morbidity and resource utilization in a neonatal intensive care unit (NICU) setting using primary nursing. RESULTS: Consistency of nursing caregivers served as a powerful mediator of length of stay and the duration of mechanical ventilation, supplemental oxygen therapy and parenteral nutrition. Analysis of nursing intensity indicators revealed that a mix of professional nurses and assistive personnel was effective. CONCLUSIONS: Providing consistency of nursing caregivers may significantly improve both health and economic outcomes. New evidence was found to support the efficacy of the primary nursing model in the NICU. IMPLICATIONS FOR NURSING MANAGEMENT: Designing nursing care delivery systems in acute inpatient settings with an emphasis on consistency of nursing caregivers could improve health outcomes, increase organizational effectiveness, and enhance satisfaction of nursing staff, patients, and families. PMID- 22074303 TI - Exploring the relationship between job satisfaction and nursing group outcome attainment capability in nurse administrators. AB - AIM: To examine the relationship between job satisfaction and nursing group outcome attainment capability (NOAC) among nurse administrators. BACKGROUND: Contributing to the nursing shortage experienced in the USA is job dissatisfaction and a sense of powerlessness. The potential to achieve power exists within nursing and is realized when nurses achieve their goals. Nurse administrators can positively impact their settings by achieving these goals as they engage in the process of NOAC. However, little is known about the relationship between nurse administrators, job satisfaction and NOAC. METHOD: In this non-experimental study, nurse administrators (n = 20) employed in mid-size urban and suburban hospitals were recruited using convenience sampling. Using an on-line format, participants completed the Minnesota Satisfaction Questionnaire to measure job satisfaction and the Sieloff-King Assessment of Group Outcome Attainment within Organizations to measure NOAC. RESULTS: Moderately strong and strong significant correlations (P < 0.003) were found between job satisfaction and nursing group outcome attainment capability (intrinsic satisfaction r = 0.800; extrinsic satisfaction r = 0.650; total satisfaction r = 0.770). CONCLUSION: To increase job satisfaction, it is important that nurse administrators have the power to achieve their professional goals. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse administrators can potentially increase their job satisfaction by achieving their professional goals. PMID- 22074304 TI - Group power through the lens of the 21st century and beyond: further validation of the Sieloff-King Assessment of Group Power within Organizations. AB - AIM: The purpose was to determine the content validity of a semantic revision of items on a reliable and valid instrument, the Sieloff-King Assessment of Group Power within Organizations (SKAGPO). BACKGROUND: Research participants expressed negative perceptions regarding the use of the concept of 'power' in SKAGPO items. The SKAGPO is the only instrument measuring a nursing group's power or outcome attainment. METHOD: Using a survey method, the instrument and grading scale were sent to 12 expert judges. Six participants completed the grading scale. RESULTS: The Content Validity Index (CVI) for seven questions was at or above 83% agreement. Overall, the CVI for the eight revised questions was 93.75%. Subsequently, the instrument was renamed the Sieloff-King Assessment of Group Outcome Attainment within Organizations (SKAGOAO). CONCLUSIONS: The semantic revision demonstrated content validity for the revised SKAGOAO. When used by nursing groups to assess their level of outcome attainment, the instrument should continue to be psychometrically evaluated. IMPLICATIONS FOR NURSING MANAGEMENT: A nursing group of any size can use the SKAGOAO to both assess the group's level of outcome attainment or empowerment and direct plans to further improve that level. PMID- 22074305 TI - Nurse managers' challenges in project management. AB - AIM: To analyse the challenges that nurse managers meet in project management. BACKGROUND: Project management done by nurse managers has a significant role in the success of projects conducted in work units. METHODS: The data were collected by open interviews (n = 14). The participants were nurse managers, nurses and public health nurses. Data analysis was carried out using qualitative content analysis. RESULTS: The three main challenges nurse managers faced in project management in health-care work units were: (1) apathetic organization and management, (2) paralysed work community and (3) cooperation between individuals being discouraged. CONCLUSIONS: Nurse managers' challenges in project management can be viewed from the perspective of the following paradoxes: (1) keeping up projects-ensuring patient care, (2) enthusiastic management-effective management of daily work and (3) supporting the work of a multiprofessional team-leadership of individual employees. IMPLICATIONS FOR NURSING MANAGEMENT: It is important for nurse managers to learn to relate these paradoxes to one another in a positive way. Further research is needed, focusing on nurse managers' ability to promote workplace spirituality, nurse managers' emotional intelligence and their enthusiasm in small projects. PMID- 22074306 TI - A theoretical model of ageing hospital nurses' well-being at work. AB - AIM: To describe the development process of a theoretical model of ageing hospital nurses' well-being at work and the subsequent testing of the model itself. BACKGROUND: Factors evoking well-being at work need to be identified to promote nurses' well-being. METHOD: Qualitative data (n = 21) from ageing hospital nurses, consisting of interviews, diaries and open data collection forms were collected and analysed using grounded theory method. Based on the finding, a survey was developed. Quantitative data (n = 328) were collected from hospital nurses born between the years 1948-1962. Explorative factor analysis was used to create the theoretical model. RESULTS: The main concepts of the model were nurse nurse interaction, nurse-patient interaction and patient-care centeredness. CONCLUSION: According to the theoretical model, well-being at work can be described as nurses' experience of collaboration, cooperation and togetherness with other nurses in a supporting and caring work environment. The aim and possibility of high-quality patient care, in a spirit where nurses and nursing are appreciated, were also revealed. IMPLICATIONS FOR NURSING MANAGEMENT: The importance of nurse-nurse interaction and nurse-patient interaction as well as ageing nurses' patient-care centeredness needs to be taken into account in nursing management and leadership. PMID- 22074307 TI - Leadership and job satisfaction among Azorean hospital nurses: an application of the situational leadership model. AB - AIMS: The aim of this study was to describe nurse managers' leadership behaviours, comparing them with staff nurses' perceptions of their leader's leadership, as well as to determine if leadership components affect job satisfaction among staff nurses. BACKGROUND: Understanding the leadership phenomenon using a detailed theoretical framework, such as the situational leadership model, allows for the deconstruction of leadership into small segments, thereby producing a vast but detailed picture of the process involved in leading people. METHOD: This quantitative, descriptive, inferential and correlational study involved the participation of 266 nurses (managers and staff) from two public Portuguese Azorean hospitals. INSTRUMENTS: The Leadership Effectiveness and Adaptability Description questionnaire, developed by Hersey and Blanchard, was used to assess leadership behaviours. A job satisfaction instrument, developed by the authors, was also used to determine staff nurses' satisfaction. RESULTS: The study revealed important differences between nurse managers and staff nurses regarding the perception of leadership components. Low levels of job satisfaction among staff nurses were detected. It was also found that some leadership components are related to staff nurses' satisfaction. CONCLUSIONS: Nurse managers must be aware of their leadership, applying appropriate styles, thereby developing their staff nurses' skills while promoting their professional satisfaction. IMPLICATIONS FOR NURSING MANAGEMENT: Leadership is a complex process that is not separable from job satisfaction. Promoting effective leadership through formal training among nurse managers may translate into having more satisfied nurses, better nursing care, and stronger leadership. PMID- 22074308 TI - Development of a model of situational leadership in residential care for older people. AB - AIM: The aim of the present study was to present the process used to develop a composite model of situational leadership enacted within a person-centred nursing framework in residential care. BACKGROUND: Transforming the culture of the residential unit from a restrictive institution to a vibrant community of older adults requires transformational leadership. Situational leadership is one form of transformational leadership, which claims that there is not one leadership style that works in all situations. METHOD: A model of situational leadership in residential care was developed through a series of systematic steps that identified direct linkages between situational leadership and the main constructs of the Person-Centred Nursing Framework. The process included reviewing the evidence, undertaking a comparative analysis, identifying key concepts, connecting the concepts and developing a model. CONCLUSION: A conceptual model is presented which integrates person-centredness with leadership thinking in order to effectively impact on the follower's performance in managing the care environment and delivering person-centred care. IMPLICATIONS FOR NURSING MANAGEMENT: Currently the model is being utilized in an action research study to evaluate the role of leaders in the practice setting of long-term care. While some of the connecting concepts have been identified in the present study, more work needs to be done to unravel these connections in further study of leaders in practice. PMID- 22074309 TI - Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis. AB - Diagnosis of invasive aspergillosis (IA) remains a challenge as the clinical manifestations are not specific, and a histological diagnosis is often unfeasible. The 2002 European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria for classification of cases into possible, probable or proven were revised in 2008. Our objective was to analyze the impact of these revisions on the diagnosis of IA. A retrospective analysis of 589 high risk patient-episodes revealed that 125 of 155 'possible' (81%) and 12 of 16 'probable' (75%) cases of IA should be changed to 'non-classifiable' when the new criteria were applied. We concluded, as expected, that the 2008 EORTC/MSG revised definitions reduced the number of cases classified as 'possible' IA, but additionally, there has been a dramatic reduction in 'probable' cases. These changes have significant implications on the interpretation of clinical trial data based on EORTC/MSG classifications. PMID- 22074310 TI - Disseminated sporotrichosis in a patient with a past history of lepromatous leprosy: a case report. AB - Disseminated sporotrichosis is uncommon and usually occurs in patients who are immunodeficient. Here we describe a male patient who was otherwise in good physical condition, who presented with disseminated sporotrichosis. The only significant event in his past medical history was lepromatous leprosy which had been treated 42 years earlier. PMID- 22074311 TI - Interpreting oral health-related quality of life data. AB - The most common way of presenting data from studies using quality of life or patient-based outcome (PBO) measures is in terms of mean scores along with testing the statistical significance of differences in means. We argue that this is insufficient in and of itself and call for a more comprehensive and thoughtful approach to the reporting and interpretation of data. PBO scores (and their means for that matter) are intrinsically meaningless, and differences in means between groups mask important and potentially different patterns in response within groups. More importantly, they are difficult to interpret because of the absence of a meaningful benchmark. The minimally important difference (MID) provides that benchmark to assist interpretability. This commentary discusses different approaches (distribution-based and anchor-based) and specific methods for assessing the MID in both longitudinal and cross-sectional studies, and suggests minimum standards for reporting and interpreting PBO measures in an oral health context. PMID- 22074312 TI - From 1D to 3D single-crystal-to-single-crystal structural transformations based on linear polyanion [Mn4(H2O)18WZnMn2(H2O)2(ZnW9O34)2]4-. AB - A 1D anionic polyoxometalate, [Mn(4)(H(2)O)(18)WZnMn(2)(H(2)O)(2)(ZnW(9)O(34))(2)](4-), undergoes 1D to 3D single-crystal-to-single-crystal structural transformations that are induced by transition-metal cations (Co(2+) and Cu(2+)) and solvent molecules. These solid materials present interesting catalytic activity for the oxidative aromatization of Hantzsch 1,4-dihydropyridines that is dependent on the inserted heterogeneous metal cations. PMID- 22074313 TI - (-)-Epigallocatechin-3-gallate: a novel storage medium for avulsed teeth. AB - The purpose of the present study was to evaluate the efficacy of (-) epigallocatechin-3-gallate (EGCG) in maintaining the vitality of human periodontal ligament (PDL) cells when used as a storage medium for avulsed teeth prior to replantation. Thirty freshly extracted single-rooted human teeth with closed apices were randomly assigned to three experimental groups with 10 samples per group and immersed in one of the storage media: EGCG, Hank's balanced salt solution (HBSS), or milk for 2 h. The PDL cells were dissociated by an enzyme treatment with collagenase and trypsin. The cells were then labeled with 0.4% Trypan blue for the determination of viability. The result showed that EGCG group had the highest percentage of cell viability, followed by HBSS and milk group, in descending order. PMID- 22074314 TI - Crystallization of fluorescent quantum dots within a three-dimensional bio organic template of actin filaments and lipid membranes. AB - Biological molecules and molecular self-assemblies are promising templates to organize well-defined inorganic nanostructures. We demonstrate the ability of a self-assembled three-dimensional crystal template of helical actin protein filaments and lipids bilayers to generate a hierarchical self-assembly of quantum dots. Functionnalized tricystein peptidic quantum dots (QDs) are incorporated during the dynamical self-assembly of this actin/lipid template resulting in the formation of crystalline fibers. The crystal parameters, 26.5*18.9*35.5 nm3, are imposed by the membrane thickness, the diameter, and the pitch of the actin self assembly. This process ensures the high quality of the crystal and results in unexpected fluorescence properties. This method of preparation offers opportunities to generate crystals with new symmetries and a large range of distance parameters. PMID- 22074315 TI - Quantification and recognition of parkinsonian gait from monocular video imaging using kernel-based principal component analysis. AB - BACKGROUND: The computer-aided identification of specific gait patterns is an important issue in the assessment of Parkinson's disease (PD). In this study, a computer vision-based gait analysis approach is developed to assist the clinical assessments of PD with kernel-based principal component analysis (KPCA). METHOD: Twelve PD patients and twelve healthy adults with no neurological history or motor disorders within the past six months were recruited and separated according to their "Non-PD", "Drug-On", and "Drug-Off" states. The participants were asked to wear light-colored clothing and perform three walking trials through a corridor decorated with a navy curtain at their natural pace. The participants' gait performance during the steady-state walking period was captured by a digital camera for gait analysis. The collected walking image frames were then transformed into binary silhouettes for noise reduction and compression. Using the developed KPCA-based method, the features within the binary silhouettes can be extracted to quantitatively determine the gait cycle time, stride length, walking velocity, and cadence. RESULTS AND DISCUSSION: The KPCA-based method uses a feature-extraction approach, which was verified to be more effective than traditional image area and principal component analysis (PCA) approaches in classifying "Non-PD" controls and "Drug-Off/On" PD patients. Encouragingly, this method has a high accuracy rate, 80.51%, for recognizing different gaits. Quantitative gait parameters are obtained, and the power spectrums of the patients' gaits are analyzed. We show that that the slow and irregular actions of PD patients during walking tend to transfer some of the power from the main lobe frequency to a lower frequency band. Our results indicate the feasibility of using gait performance to evaluate the motor function of patients with PD. CONCLUSION: This KPCA-based method requires only a digital camera and a decorated corridor setup. The ease of use and installation of the current method provides clinicians and researchers a low cost solution to monitor the progression of and the treatment to PD. In summary, the proposed method provides an alternative to perform gait analysis for patients with PD. PMID- 22074317 TI - A systematic review of the evidence base for Schema Therapy. AB - Schema Therapy is becoming an increasingly popular psychological model for working with individuals who have a variety of mental health and personality difficulties. The aim of this review is to look at the current evidence base for Schema Therapy and highlight directions for further research. A systematic search of the literature was conducted up until January 2011. All studies that had clinically tested the efficacy of Schema Therapy as described by Jeffrey Young (1994 and 2003) were considered. These studies underwent detailed quality assessments based on Scottish Intercollegiate Guidelines Network (SIGN-50) culminating in 12 studies being included in the review. The culminative message (both from the popularity of this model and the medium-to-large effect sizes) is of a theory that has already demonstrated clinically effective outcomes in a small number of studies and that would benefit from ongoing research and development with complex client groups. It is imperative that psychological practice be guided by high-quality research that demonstrates efficacious, evidence-based interventions. It is therefore recommended that researchers and clinicians working with Schema Therapy seek to build on these positive outcomes and further demonstrate the clinical effectiveness of this model through ongoing research. PMID- 22074316 TI - Maximizing tumour exposure to anti-neuropilin-1 antibody requires saturation of non-tumour tissue antigenic sinks in mice. AB - BACKGROUND AND PURPOSE: Neuropilin-1 (NRP1) is a VEGF receptor that is widely expressed in normal tissues and is involved in tumour angiogenesis. MNRP1685A is a rodent and primate cross-binding human monoclonal antibody against NRP1 that exhibits inhibition of tumour growth in NPR1-expressing preclinical models. However, widespread NRP1 expression in normal tissues may affect MNRP1685A tumour uptake. The objective of this study was to assess MNRP1685A biodistribution in tumour-bearing mice to understand the relationships between dose, non-tumour tissue uptake and tumour uptake. EXPERIMENTAL APPROACH: Non-tumour-bearing mice were given unlabelled MNRP1685A at 10 mg.kg(-1) . Tumour-bearing mice were given (111) In-labelled MNRP1685A along with increasing amounts of unlabelled antibody. Blood and tissues were collected from all animals to determine drug concentration (unlabelled) or radioactivity level (radiolabelled). Some animals were imaged using single photon emission computed tomography - X-ray computed tomography. KEY RESULTS: MNRP1685A displayed faster serum clearance than pertuzumab, indicating that target binding affected MNRP1685A clearance. I.v. administration of (111) In labelled MNRP1685A to tumour-bearing mice yielded minimal radioactivity in the plasma and tumour, but high levels in the lungs and liver. Co-administration of unlabelled MNRP1685A with the radiolabelled antibody was able to competitively block lungs and liver radioactivity uptake in a dose-dependent manner while augmenting plasma and tumour radioactivity levels. CONCLUSIONS AND IMPLICATIONS: These results indicate that saturation of non-tumour tissue uptake is required in order to achieve tumour uptake and acceptable exposure to antibody. Utilization of a rodent and primate cross-binding antibody allows for translation of these results to clinical settings. PMID- 22074318 TI - A programmed polymer folding: click and clip construction of doubly fused tricyclic and triply fused tetracyclic polymer topologies. AB - A tandem alkyne-azide addition, i.e., click, and an olefin metathesis condensation, i.e., clip, reactions in conjunction with an electrostatic self assembly and covalent fixation (ESA-CF) process, have been demonstrated as effective means to produce constructions of programmed folding of polymers having doubly fused tricyclic and triply fused tetracyclic topologies. Thus, a series of cyclic poly(tetrahydrofuran), poly(THF), precursors having an allyloxy group and an alkyne group (Ia), an allyloxy group and an azide group (Ib), and two alkyne groups (Ic) at the opposite positions was prepared by means of the ESA-CF method. The subsequent click reactions of Ia with a linear telechelic poly(THF) precursor having azide end groups (Id) and of Ib with Ic afforded a bridged dicyclic polymer (IIa) and a tandem spiro tricyclic precursor (IIb), respectively, both having two allyloxy groups at the opposite positions of the ring units. Finally, the intramolecular metathesis condensation reaction of IIa and of IIb in the presence of a Grubbs catalyst was performed to construct effectively a doubly fused tricyclic and a triply fused tetracyclic polymer topologies (III and IV), respectively. PMID- 22074319 TI - Regional variation and determinants of vitamin D status in sunshine-abundant Thailand. AB - BACKGROUND: Vitamin D insufficiency is highly prevalent. Most of the studies concerning vitamin D status were generated from countries situated at temperate latitudes. It is less clear what the extent of vitamin D insufficiency is in countries situated in the tropics and how geographical regions within country would affect vitamin D status. In the present study, we investigated vitamin D status in Thais according to geographical regions and other risk factors. METHODS: Subjects consisted of 2,641 adults, aged 15 - 98 years, randomly selected from the Thai 4th National Health Examination Survey (2008-9) cohort. Serum 25 hydroxyvitamin D were measured by liquid chromatography/tandem mass spectrometry. Data were expressed as mean +/- SE. RESULTS: Subjects residing in Bangkok, the capital city of Thailand, had lower 25(OH)D levels than other parts of the country (Bangkok, central, northern, northeastern and southern regions: 64.8 +/- 0.7, 79.5 +/- 1.1, 81.7 +/- 1.2, 82.2 +/- 0.8 and 78.3 +/- 1.3 nmol/L, respectively; p < 0.001). Within each region, except for the northeastern part of the country, subjects living inside municipal areas had lower circulating 25(OH)D (central, 77.0 +/- 20.9 nmol/L vs 85.0 +/- 22.1 nmol/L, p < 0.001; north 79.3 +/- 22.1 nmol/L vs 86.8 +/- 21.8 nmol/L, p < 0.001; northeast 84.1 +/- 23.3 nmol/L vs 87.3 +/- 20.9 nmol/L, p = 0.001; south, 76.6 +/- 20.5 nmol/L vs 85.2 +/- 24.7 nmol/L, p < 0.001). Overall, the prevalence of vitamin D insufficiency was 64.6%, 46.7%, and 33.5% in Bangkok, municipal areas except Bangkok, and outside municipal area in other parts of the country, respectively. In addition, the prevalence of vitamin D insufficiency according to geographical regions was 43.1%, 39.1%, 34.2% and 43.8% in the central, north, northeast and south, respectively. After controlling for covariates in multiple linear regression analysis, the results showed that low serum 25(OH)D levels were associated with being female, younger age, living in urban and Bangkok. CONCLUSIONS: Vitamin D insufficiency is common and varies across geographical regions in Thailand. PMID- 22074320 TI - Head injury from a bungee run. AB - An adaptation of bungee jumping, 'bungee running', involves participants attempting to run as far as they can whilst connected to an elastic rope which is anchored to a fixed point. Usually considered a safe recreational activity, we report a potentially life-threatening head injury following a bungee running accident. PMID- 22074321 TI - Hyaluronic acid enhances gene delivery into the cochlea. AB - Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application. PMID- 22074323 TI - The development of 13-valent pneumococcal conjugate vaccine and its possible use in adults. AB - INTRODUCTION: Worldwide, Streptococcus pneumoniae causes significant morbidity and mortality. The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for use in persons aged 65 years and over and in adults with certain chronic medical conditions. Pneumococcal conjugate vaccines (PCVs) have been developed for use in infants and children aged less than 5 years, and are being studied for use in adult populations. AREAS COVERED: The different types of pneumococcal vaccines are discussed. Studies comparing PPSV23 and PCVs, as well as the results of the widespread use of 7-valent PCV are covered. The possible extension of the use of 13-valent PCV to adults, particularly to vulnerable populations, is discussed. The MEDLINE database was used to identify relevant studies from literature published in English between January 1977 and January 2011. All studies of adults aged over 18 years were considered for the review. EXPERT OPINION: Elderly individuals and adults with chronic medical conditions who are at increased risk for pneumococcal disease would benefit from more effective prevention than is provided by the currently recommended PPSV23. PMID- 22074322 TI - Inhibition of HCV 3a genotype entry through host CD81 and HCV E2 antibodies. AB - BACKGROUND: HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV. METHODS AND RESULT: The present study elaborated the role of CD81 and HCV glycoprotein E2 in HCV entry using retroviral pseudo-particles of 3a local genotype. Our results demonstrated that HCV specific antibody E2 and host antibody CD81 showed dose- dependent inhibition of HCV entry. HCV E2 antibody showed 50% reduction at a concentration of 1.5 +/- 1 MUg while CD81 exhibited 50% reduction at a concentration of 0.8 +/- 1 MUg. In addition, data obtained with HCVpp were also confirmed with the infection of whole virus of HCV genotype 3a in liver cells. CONCLUSION: Our data suggest that HCV specific E2 and host CD81 antibodies reduce HCVpp entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer. PMID- 22074324 TI - Nurses' decision on seclusion: patient characteristics, contextual factors and reflexivity in teams. AB - While many characteristics of patients, professionals and facilities with relevance to seclusion rates have been investigated, their relative importance is unclear. Virtually no attention has been paid to team processes and reflexivity in relation to decision making on seclusion. The aim of this paper is to estimate the effects of these factors on nurse decision making on seclusion. Sixty Dutch psychiatric nurses of four closed wards reported team reflexivity and their tendency to seclude a theoretical patient. Approachability (whether there was a good or hardly any possibility to communicate with the patient), staffing level and confidence within the team had the greatest impact on the decision to seclude. Intra class correlation was 0.30. There was a large interaction effect of reflexivity with team 4, and team reflexivity was highly correlated with team tendency to avoid seclusion. In nurses' decision on seclusion, the effects of 'pure' patient characteristics are small as compared with the effects of interpersonal and contextual factors, and nurses vary widely in their judgement. Team reflexivity is related to the tendency to prevent seclusion. PMID- 22074325 TI - Estimating the preappearance interval from temperature in Creophilus maxillosus L. (Coleoptera: Staphylinidae). AB - Some carrion insects appear on carcasses late in decomposition. While using these late-arriving taxa to estimate postmortem interval, it is vital to accurately estimate an interval preceding their appearance on a cadaver called the preappearance interval (PAI). This paper tests the possibilities of a PAI estimation from temperature in case of late-arriving, predatory carrion beetle Creophilus maxillosus. The relationship between temperature and PAI of adult and larval C. maxillosus was modeled using the results of a large-scale experiment on succession in forests of Central Europe. In both stages, PAI was found to be strongly, inversely related to temperature averaged for the duration of PAI. The PAI estimation from mean degree-day accumulations (mDDA), estimated DDA, and "PAI*T" functions were tested using external successional data. The greatest accuracy of PAI estimates was achieved using an exponential "PAI*T" function. PMID- 22074327 TI - Diets enriched with a Jerte Valley cherry-based nutraceutical product reinforce nocturnal behaviour in young and old animals of nocturnal (Rattus norvegicus) and diurnal (Streptopelia risoria) chronotypes. AB - The decline in melatonin secretion with age seems to be one of the major reasons for increased sleep disruption in older animals. Previously, we showed that the administration with melatonin or its precursor, tryptophan, improved activity/rest rhythms in aged individuals. Here, it was evaluated the effect of a 10-day consumption of a Jerte Valley cherry-based nutraceutical product (patent no. ES2342141B1), which contains high levels of tryptophan, serotonin and melatonin, on the activity/rest rhythms of young and old rats (Rattus norvegicus) and ringdoves (Streptopelia risoria) as representatives of animals with nocturnal and diurnal habits, respectively, and its possible relationship with the serum levels of melatonin and glucose. Total diurnal and nocturnal activity pulses were logged at control, during, and up to 3 days after the treatment. Melatonin and glucose were measured with ELISA and testing kits respectively. In both young and old rats, the intake of the cherry nutraceutical decreased diurnal activity, whereas nocturnal activity increased. The opposite effect was observed for ringdoves. The treatment increased the circulating levels of melatonin in both species and restored the amplitude of the activity rhythm in the old animals to that of the non-treated young groups. The consumption of a Jerte Valley cherry based nutraceutical product may help to counteract the impaired activity/rest rhythm found in aged animals. PMID- 22074326 TI - Perspective on the human cough reflex. AB - This review dissects the complex human cough reflex and suggests hypotheses about the evolutionary basis for the reflex. A mechanosensory-induced cough reflex conveys through branches of myelinated Adelta nerve fibers is not chemically reactive (i.e., capsaicin, bradykinin); possibly, its evolution is to prevent the harmful effects of aspiration of gastric or particulate contents into the lungs. This became necessary as the larynx moves closer to the opening of the esophagus as human ancestors adapt phonation over olfaction beginning less than 10 million years ago. The second type of cough reflex, a chemosensory type, is carried by unmyelinated C fibers. Supposedly, its origin dates back when prehistoric humans began living in close proximity to each other and were at risk for infectious respiratory diseases or irritant-induced lung injury. The mechanism for the latter type of cough is analogous to induced pain after tissue injury; and, it is controlled by the identical transient receptor potential vanilloid cation channel (TRPV1). The airways do not normally manifest nociceptive pain from a stimulus but the only consistent response that capsaicin and lung inflammation provoke in healthy human airways is cough. TRPA1, another excitatory ion channel, has been referred to as the "irritant receptor" and its activation also induces cough. For both types of cough, the motor responses are identical and via coordinated, precisely-timed and sequential respiratory events orchestrated by complex neuromuscular networking of the diaphragm, chest and abdominal respiratory muscles, the glottis and parts of the brain. PMID- 22074328 TI - Laboratory study to assess causative factors affecting temporal changes in filtering facepiece respirator fit: part I - pilot study. AB - The National Institute for Occupational Safety and Health is conducting a first of-its-kind study that will assess respirator fit and facial dimension changes as a function of time and improve the scientific basis for decisions on the periodicity of fit testing. A representative sample of 220 subjects wearing filtering-facepiece respirators (FFR) will be evaluated to investigate factors that affect changes in respirator fit over time. The objective of this pilot study (n = 10) was to investigate the variation in fit test data collected in accordance with the study protocol. Inward leakage (IL) and filter penetration were measured for each donned respirator, permitting the calculation of face seal leakage (FSL) and fit factor (FF). The study included only subjects who (a) passed one of the first three fit tests (FF >= 100), and (b) demonstrated through a series of nine donnings that they achieved adequate fit (90th percentile FSL was <= 0.05). Following the respirator fit tests, 3-D scans of subjects were captured, and height, weight, and 13 traditional anthropometric facial dimensions were measured. The same data were collected 2 and 4 weeks after baseline. The mean change in FSL for the 10 subjects was 0.044% between Visits 1 and 2, and was 0.229% between Visits 1 and 3. Technicians achieved at least moderate reliability for all manual measurements except nose protrusion. Filter penetration was generally less than 0.03%. Geometric mean fit factors were not statistically different among the three visits. The large variability was observed with different respirator samples for the same model, between subjects (inter), and within each subject (intra). Although variability was observed, adequate fit was maintained for all 10 subjects. Pilot scans collected show subject faces remained the same over the 4 weeks. The consistent results during the pilot study indicate that the methods and procedures are appropriate for the 3-year main study. In addition, this baseline fit change data will be compared with future fit changes to determine if the changes are meaningful. PMID- 22074329 TI - Examining the association between emotion regulation difficulties and probable posttraumatic stress disorder within a sample of African Americans. AB - This study examined the associations between emotion dysregulation and probable posttraumatic stress disorder (PTSD) among 180 African American undergraduates enrolled in a historically black college in the southern United States. Trauma exposed participants with probable PTSD reported significantly higher levels of overall emotion dysregulation and the specific dimensions of lack of emotional acceptance, difficulties engaging in goal-directed behavior when upset, difficulties controlling impulsive behaviors when distressed, and limited access to effective emotion regulation strategies than participants without Criterion A traumatic exposure and those with Criterion A traumatic exposure but no PTSD (controlling for age and negative affect). Furthermore, results indicated that participants with Criterion A traumatic exposure but no PTSD were significantly less likely to report difficulties controlling impulsive behaviors when distressed and limited access to effective emotion regulation strategies than participants without Criterion A traumatic exposure (controlling for age and negative affect). These findings extend extant research on the role of emotion dysregulation in PTSD, thus providing support for the relevance of emotion dysregulation to PTSD among African American adults in particular. PMID- 22074330 TI - The neuropathology, pathophysiology and genetics of multiple system atrophy. AB - Multiple system atrophy (MSA) is an unrelenting, sporadic, adult-onset, neurodegenerative disease of unknown aetiology. Its clinically progressive course is characterized by a variable combination of parkinsonism, cerebellar ataxia and/or autonomic dysfunction. Neuropathological examination often reveals gross abnormalities of the striatonigral and/or olivopontocerebellar systems, which upon microscopic examination are associated with severe neuronal loss, gliosis, myelin pallor and axonal degeneration. MSA is a member of a diverse group of neurodegenerative disorders termed alpha-synucleinopathies, due to the presence of abnormal alpha-synuclein positive cytoplasmic inclusions in oligodendrocytes, termed glial cytoplasmic inclusions. These are the hallmark neuropathological lesion of MSA and are thought to play a central role in the pathogenesis of the disease. In this review, neuropathological features of MSA are described in detail, along with recent advances in the pathophysiology and genetics of the disease. Our current knowledge of the expression and accumulation of alpha synuclein, and efforts to model the disease in vitro and in vivo, are emphasized in this paper and have helped formulate a working hypothesis for the pathogenesis of MSA. PMID- 22074331 TI - Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation. AB - Numerous inflammatory conditions are associated with elevated YKL-40 expression by infiltrating macrophages. Thus, we were surprised to observe minimal macrophage and abundant astrocyte expression of YKL-40 in neuroinflammatory conditions. The aims of the current study were to better delineate this discrepancy, characterize the factors that regulate YKL-40 expression in macrophages and astrocytes and study whether YKL-40 expression correlates with cell morphology and/or activation state. In vitro, macrophages expressed high levels of YKL-40 that was induced by classical activation and inhibited by alternative activation. Cytokines released from macrophages induced YKL-40 transcription in astrocytes that was accompanied by morphological changes and altered astrocytic motility. Because coculturing of astrocytes and macrophages did not reverse this in vitro expression pattern, additional components of the in vivo central nervous system (CNS) milieu must be required to suppress macrophage and induce astrocyte expression of YKL-40. PMID- 22074332 TI - An iterative approach of protein function prediction. AB - BACKGROUND: Current approaches of predicting protein functions from a protein protein interaction (PPI) dataset are based on an assumption that the available functions of the proteins (a.k.a. annotated proteins) will determine the functions of the proteins whose functions are unknown yet at the moment (a.k.a. un-annotated proteins). Therefore, the protein function prediction is a mono directed and one-off procedure, i.e. from annotated proteins to un-annotated proteins. However, the interactions between proteins are mutual rather than static and mono-directed, although functions of some proteins are unknown for some reasons at present. That means when we use the similarity-based approach to predict functions of un-annotated proteins, the un-annotated proteins, once their functions are predicted, will affect the similarities between proteins, which in turn will affect the prediction results. In other words, the function prediction is a dynamic and mutual procedure. This dynamic feature of protein interactions, however, was not considered in the existing prediction algorithms. RESULTS: In this paper, we propose a new prediction approach that predicts protein functions iteratively. This iterative approach incorporates the dynamic and mutual features of PPI interactions, as well as the local and global semantic influence of protein functions, into the prediction. To guarantee predicting functions iteratively, we propose a new protein similarity from protein functions. We adapt new evaluation metrics to evaluate the prediction quality of our algorithm and other similar algorithms. Experiments on real PPI datasets were conducted to evaluate the effectiveness of the proposed approach in predicting unknown protein functions. CONCLUSIONS: The iterative approach is more likely to reflect the real biological nature between proteins when predicting functions. A proper definition of protein similarity from protein functions is the key to predicting functions iteratively. The evaluation results demonstrated that in most cases, the iterative approach outperformed non-iterative ones with higher prediction quality in terms of prediction precision, recall and F-value. PMID- 22074334 TI - Introduction to a Virtual Special Issue on calcium signalling in plants. PMID- 22074333 TI - MicroRNA modulation in complex regional pain syndrome. AB - BACKGROUND: Aberrant expression of small noncoding RNAs called microRNAs (miRNAs) is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS) a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification. METHODS: We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions. RESULTS: Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF), interleukin1 receptor antagonist (IL1Ra) and monocyte chemotactic protein-1 (MCP1) were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with comorbidities such as headache, thyroid disorder and use of narcotics and antiepileptic drugs. CONCLUSIONS: miRNA profiles can be useful in patient stratification and have utility as potential biomarkers for pain. Differentially expressed miRNAs can provide molecular insights into gene regulation and could lead to new therapeutic intervention strategies for CRPS. PMID- 22074335 TI - Wetlands and the global carbon cycle: what might the simulated past tell us about the future? PMID- 22074336 TI - Delivering resistance to a major constraint for rain-fed rice production. PMID- 22074337 TI - Multi-factor global change experiments: what have we learned about terrestrial carbon storage and exchange? PMID- 22074338 TI - Mechanistic causes of tree drought mortality: recent results, unresolved questions and future research needs. PMID- 22074339 TI - Ectomycorrhizas from a Lower Eocene angiosperm forest. AB - The development of mycorrhizal associations is considered a key innovation that enabled vascular plants to extensively colonize terrestrial habitats. Here, we present the first known fossil ectomycorrhizas from an angiosperm forest. Our fossils are preserved in a 52 million-yr-old piece of amber from the Tadkeshwar Lignite Mine of Gujarat State, western India. The amber was produced by representatives of Dipterocarpaceae in an early tropical broadleaf forest. The ectomycorrhizas were investigated using light microscopy and field emission scanning electron microscopy. Dissolving the amber surrounding one of the fossils allowed ultrastructural analyses and Raman spectroscopy. Approx. 20 unramified, cruciform and monopodial-pinnate ectomycorrhizas are fossilized adjacent to rootlets, and different developmental stages of the fossil mycorrhizas are delicately preserved in the ancient resin. Compounds of melanins were detectable in the dark hyphae. The mycobiont, Eomelanomyces cenococcoides gen. et spec. nov., is considered to be an ascomycete; the host is most likely a dipterocarp representative. An early ectomycorrhizal association may have conferred an evolutionary advantage on dipterocarps. Our find indicates that ectomycorrhizas occurred contemporaneously within both gymnosperms (Pinaceae) and angiosperms (Dipterocarpaceae) by the Lower Eocene. PMID- 22074340 TI - The rhenium tris(dithiolene) electron transfer series: calibrating covalency. AB - Four members of the rhenium tris(dithiolene) electron transfer series have been prepared, [Re(S(2)C(2)R(2))(3)](z) {R = Ph, z = 1+ (1), 0 (2), 1- (3); R = CN, z = 2- (4)}, with the anions in 3 and 4 structurally characterized. The intraligand C-S and C-C bond lengths for 3 vs 2 are indicative of ligand reduction concomitant with an overall distorted trigonal prismatic geometry (Theta = 26.3 degrees cf. 3.8 degrees in 2). The distorted octahedral ReS(6) polyhedron in 4 (Theta = 38.3 degrees ) indicates reduction of the metal to a Re(IV) d(3) central ion. This series has been probed by sulfur K-edge X-ray absorption spectroscopy (XAS), and the electronic structures are unambiguously defined as follows: [Re(V)(L(3)(4-))](1+) (S = 0) for the monocation in 1; [Re(V)(L(3)(5-*))](0) (S = (1)/(2)) for neutral 2; [Re(V)(L(3)(6-))](1-) (S = 0) for the monoanion in 3; and [Re(IV)(L(3)(6-))](2-) (S = (1)/(2)) for the dianion in 4. The sulfur 3p character in the frontier orbitals-the covalency-is estimated by two different approaches. Method A utilizes the radial dipole integral (I(s)) derived from the S 1s -> 4p transition, whereas method B, involves time-dependent density functional theoretical (TD-DFT) calculation of the pre-edge transitions and calibrated to the intensity in [Re(pdt)(3)] (pdt(2-) = 1,2-diphenyl-1,2 dithiolate). The two estimates are contrasted for the rhenium series and extended to the [V(pdt)(3)](0/1-), and [Mo(mdt)(3)](0/1-/2-) (mdt(2-) = 1,2-dimethyl-1,2 dithiolate) series, ultimately providing a refined description of the contested electronic structure of neutral molybdenum (and tungsten) tris(dithiolenes) compounds. PMID- 22074342 TI - Order-disorder transition in supramolecular polymers. AB - In supramolecular polymers, directional interactions control the constituting units connectivity, but dispersion forces may conspire to make complex organizations. Here we report on the long-range order and order-disorder transition (ODT) of main-chain supramolecular polymers based on poly(propylene oxide) (PPO) spacers functionalized on both ends with thymine. Below the ODT temperature (T(ODT)), these compounds are semicrystalline with a lamellar structure, showing nanophase separation between crystallized thymine planes and amorphous PPO layers. Above T(ODT), they are amorphous and homogeneous even though their X-ray scattering spectrum reveals a peak. This peak is due to correlation hole effect resulting from contrast between end-functional groups and spacer. Macroscopically, the transition is accompanied by dramatic flow and mechanical properties changes. PMID- 22074341 TI - Urban and rural variation in clustering of metabolic syndrome components in the Thai population: results from the fourth National Health Examination Survey 2009. AB - BACKGROUND: Information on the distribution of Metabolic syndrome (MetS) and its combinations by urban/rural areas in lower-middle income countries has been limited. It is not clear how the various combinations of MetS components varied by urban/rural population and if particular combinations of MetS are more common. This study aimed to estimate the prevalence of MetS and combinations of MetS components according to sex and urban/rural areas from a nationally representative sample of Thai adults. METHODS: Data from the fourth National Health Examination Survey of 19,256 Thai adults aged 20 years and over were analyzed. MetS was defined using the harmonized criteria of six international expert groups with Asian-specific cut-point for waist circumference. RESULTS: The prevalence of MetS was 23.2% among adults aged >= 20 years (19.5% in men and 26.8% in women). Among men, the prevalence of MetS in urban was higher than those in rural areas (23.1% vs 17.9%, P < 0.05), but among women, the prevalence was higher in rural areas (27.9% vs 24.5%, P < 0.05). Overall, an individual component of low high density lipoprotein (HDL) and hypertriglyceridemia were more common in rural areas, while obesity, high blood pressure and hyperglycemia were more common in urban areas. The most common combination of MetS components in men was the clustering of low HDL, hypertriglyceridemia, and high blood pressure (urban: 3.4% vs. rural: 3.9%, adjusted OR 0.9, 95%CI 0.7, 1.1). Among women, the most common combination was the clustering of obesity, low HDL, and hypertriglyceridemia (urban: 3.9% vs rural: 5.9%, adjusted OR 0.8, 95%CI 0.6, 0.9), followed by the clustering of these three components with high blood pressure (urban: 3.1% vs. rural 4.5%, adjusted OR 0.8, 95%CI 0.7, 0.9). CONCLUSION: Metabolic syndrome affects both urban and rural population with different pattern of MetS combinations. Dyslipidemia and obesity were the most common components among women in rural areas, hence, interventions to prevent and control these factors should be strengthened. PMID- 22074343 TI - The efficacy and safety of antibiotic combination therapy for infections caused by Gram-positive and Gram-negative organisms. AB - INTRODUCTION: Antibiotic combination therapy is often used to improve clinical efficacy in patients where a given therapy is thought to have limitations when used alone. However, the use of any antibacterial and perhaps more so with combination therapy comes with inherent risks. Herein the authors have evaluated both the risks and the benefits associated with the use of combination therapy. AREAS COVERED: Articles relating to the study of combination therapy were included by multiple Medline searches using relevant search terminology. Resultant publications included study by both in vitro and in vivo methodologies with clinical data coming from both observational and randomized studies. EXPERT OPINION: The majority of the data evaluating combination therapy were determined using in vitro techniques or animal models of infection. Through analyses of this information, coupled with the available clinical data, albeit limited, it is possible to identify a number of clinical situations where combination therapy can be supported. When used appropriately at optimal doses, combination therapy may offer an excellent opportunity to maximize clinical outcomes, particularly in the face of antibacterial resistance. Therefore, clinicians should evaluate carefully the risks and the potential benefits before adding additional antibiotics to standard single-drug therapies. PMID- 22074344 TI - Evaluation of an ambient noise insensitive hum-based powered wheelchair controller. AB - PURPOSE: A recently-developed assistive technology nicknamed "the Hummer" was investigated as a potential powered wheelchair controller for individuals with severe and multiple disabilities. System performance in a noisy environment was compared to that obtained with a commercial automatic speech recognition (ASR) system. METHOD: A bi-hum driving protocol was developed to allow the Hummer to serve as a powered wheelchair controller. Participants performed several virtual wheelchair driving tasks of increasing difficulty using the two systems. Custom written software recorded task execution time, number of commands issued and wall collisions, speed, and trajectory. RESULTS: The bi-hum protocol was shown to be non-intuitive and required user training. Overall, the Hummer achieved lower performance relative to ASR. Once users became accustomed to the protocol, the difference in performance between the two systems became insignificant, particularly for the higher-difficulty task. CONCLUSIONS: The Hummer provides a promising new alternative for powered wheelchair control in everyday environments for individuals with severe and multiple disabilities who are able to hum, particularly for those with severe dysarthria which precludes ASR usage. A more intuitive driving protocol is still needed to reduce user frustration and mitigate user-generated errors; recommendations on how this can be achieved are given herein. [Box: see text]. PMID- 22074345 TI - Nitrogen metabolism in Sinorhizobium meliloti-alfalfa symbiosis: dissecting the role of GlnD and PII proteins. AB - To contribute nitrogen for plant growth and establish an effective symbiosis with alfalfa, Sinorhizobium meliloti Rm1021 needs normal operation of the GlnD protein, a bifunctional uridylyltransferase/uridylyl-cleavage enzyme that measures cellular nitrogen status and initiates a nitrogen stress response (NSR). However, the only two known targets of GlnD modification in Rm1021, the PII proteins GlnB and GlnK, are not necessary for effectiveness. We introduced a Tyr >Phe variant of GlnB, which cannot be uridylylated, into a glnBglnK background to approximate the expected state in a glnD-sm2 mutant, and this strain was effective. These results suggested that unmodified PII does not inhibit effectiveness. We also generated a glnBglnK-glnD triple mutant and used this and other mutants to dissect the role of these proteins in regulating the free-living NSR and nitrogen metabolism in symbiosis. The glnD-sm2 mutation was dominant to the glnBglnK mutations in symbiosis but recessive in some free-living phenotypes. The data show that the GlnD protein has a role in free-living growth and in symbiotic nitrogen exchange that does not depend on the PII proteins, suggesting that S. meliloti GlnD can communicate with the cell by alternate mechanisms. PMID- 22074346 TI - MGOS: development of a community annotation database for Magnaporthe oryzae. AB - Magnaporthe oryzae causes rice blast disease, which is the most serious disease of cultivated rice worldwide. We previously developed the Magnaporthe grisea Orzya sativa (MGOS) database as a repository for the M. oryzae and rice genome sequences together with a comprehensive set of functional interaction data generated by a major consortium of U.S. researchers. The MGOS database has now undergone a major redesign to include data from the international blast research community, accessible with a new intuitive, easy-to-use interface. Registered database users can manually annotate gene sequences and features as well as add mutant data and literature on individual gene pages. Over 900 genes have been manually curated based on various biological databases and the scientific literature. Gene names and descriptions, gene ontology annotations, published and unpublished information on mutants and their phenotypes, responses in diverse microarray analyses, and related literature have been incorporated. Thus far, 362 M. oryzae genes have associated information on mutants. MGOS is now poised to become a one-stop repository for all structural and functional data available on all genes of this critically important rice pathogen. PMID- 22074347 TI - An avirulent tomato powdery mildew isolate induces localized acquired resistance to a virulent isolate in a spatiotemporal manner. AB - Hypersensitive response (HR) of plant cells to the attack of pathogens induces resistance to subsequent attacks by a broad spectrum of pathogens, leading to acquired resistance. In this study, we characterized the localized acquired resistance (LAR) in the epidermal cells of tomato. First, we report the discovery of a new isolate of tomato powdery mildew occurring in Japan, KTP-02, which has a different virulence spectrum compared with the previously-characterized isolate, KTP-01. Using these two isolates, we investigated LAR phenomenon in the epidermal cells of tomato plants carrying the Ol-4 resistance gene. Ol-4 encodes a nucleotide-binding site leucine-rich repeat protein that triggers HR in the epidermal cells in response to KTP-01 but not KTP-02. We mounted a single conidium of KTP-01 on a single tomato epidermal cell and then monitored the progress of HR in that cell by live microscopy. Once HR occurred in that cell, we mounted a single conidium of KTP-02 on cells adjacent to or at one-cell distance from the first challenged cells, in different time points. With a digital microscope, we consecutively tracked the progress of HR (i.e., induction of LAR) in those cells. Results showed that, in tomato plants carrying the Ol-4 gene, HR to KTP-01 results in induction of HR in the adjacent epidermal cells challenged with KTP-02. Our results show that LAR can be triggered only in adjacent cell layer and lasts 24 to 48 h after HR occurred in the first cell. We did not observe the reverse phenomenon, induced susceptibility to KTP-01 by KTP-02. Altogether, we report an advanced technique for investigating LAR phenomena, and provide data on spatiotemporal characteristics of LAR in tomato epidermal cells. PMID- 22074348 TI - Development and application of a multilocus sequence analysis method for the identification of genotypes within genus Bradyrhizobium and for establishing nodule occupancy of soybean (Glycine max L. Merr). AB - A multilocus sequence typing (MLST) method based on allelic variation of seven chromosomal loci was developed for characterizing genotypes (GT) within the genus Bradyrhizobium. With the method, 29 distinct multilocus GT were identified among 190 culture collection soybean strains. The occupancy of 347 nodules taken from uninoculated field-grown soybean plants also was determined. The bacteroid GT were either the same as or were closely related to GT identified among strains in the culture collection. Double-nodule occupancy estimates of 2.9% were much lower than values published based on serology. Of the 347 nodules examined, 337 and 10 were occupied by Bradyrhizobium japonicum and B. elkanii, respectively. The collection strains within the species B. japonicum and B. elkaniialso were compared with Bradyrhizobium cultures from other legumes. In many cases, the observed GT varied more according to their geographic origin than by their trap hosts of isolation. In other cases, there were no apparent relationships with either the legume or geographic source. The MLST method that was developed should be a useful tool in determining the influence of geographic location, temperature, season, soil type, and host plant cultivar on the distribution of GT of Bradyrhizobium spp. PMID- 22074349 TI - Socioeconomic-related health inequality in South Africa: evidence from General Household Surveys. AB - BACKGROUND: Inequalities in health have received considerable attention from health scientists and economists. In South Africa, inequalities exist in socio economic status (SES) and in access to basic social services and are exacerbated by inequalities in health. While health systems, together with the wider social determinants of health, are relevant in seeking to improve health status and health inequalities, those that need good quality health care too seldom get it. Studies on the burden of ill-health in South Africa have shown consistently that, relative to the wealthy, the poor suffer more from more disease and violence. However, these studies are based on selected disease conditions and only consider a single point in time. Trend analyses have yet to be produced. This paper specifically investigates socio-economic related health inequality in South Africa and seeks to understand how the burden of self-reported illness and disability is distributed and whether this has changed since the early 2000s. METHODS: Several rounds (2002, 2004, 2006, and 2008) of the South African General Household Surveys (GHS) data were used, with standardized and normalized self reported illness and disability concentration indices to assess the distribution of illness and disability across socio-economic groups. Composite indices of socio-economic status were created using a set of common assets and household characteristics. RESULTS: This study demonstrates the existence of socio-economic gradients in self-reported ill-health in South Africa. The burden of the major categories of ill-health and disability is greater among lower than higher socio economic groups. Even non-communicable diseases, which are frequently seen as diseases of affluence, are increasingly being reported by lower socio-economic groups. For instance, the concentration index of flu (and diabetes) declined from about 0.17 (0.10) in 2002 to 0.05 (0.01) in 2008. These results have also been confirmed internationally. CONCLUSION: The current burden and distribution of ill health indicates how critical it is for the South African health system to strive for access to and use of health services that is in line with need for such care. Concerted government efforts, within both the health sector and other social and economic sectors are therefore needed to address the significant health inequalities in South Africa. PMID- 22074350 TI - The role of disease surveillance in achieving IHR compliance by 2012. AB - The World Health Organization's revised International Health Regulations (IHR (2005)) call for member state compliance by mid-2012. Variation in disease surveillance and core public health capacities will affect each member state's ability to meet this deadline. We report on topics presented at the preconference workshop, "The Interaction of Disease Surveillance and the International Health Regulations," held at the 2010 International Society for Disease Surveillance conference in Park City, Utah. Presenters were from the Pan American Health Organization (PAHO), the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention (CDC), the Armed Forces Health Surveillance Center, U.S. Naval Research Unit Six, the Philippines' National Epidemiologic Center, and the French armed forces. The topics addressed were: an overview of the revised IHRs; disease surveillance systems implemented in Peru, the Philippines, and by the French armed forces; the capacity building efforts of the CDC; partnerships and contributions to IHR compliance from HHS; and the application of the IHRs to special populations. Results from the meeting evaluation indicate that many participants found the information useful in better understanding current efforts of the U.S. government and international organizations, areas for collaboration, and how the IHRs apply to their countries' public health systems. Topics to address at future workshops include progress and challenges to IHR implementation across all member states and additional examples of how disease surveillance supports the IHRs in resource constrained countries. The preconference workshop provided the opportunity to convene public health experts from all regions of the world. Stronger collaborations and support to better detect and respond to public health events through building sustainable disease surveillance systems will not only help member states to meet IHR compliance by 2012, but will also improve pandemic preparedness and global health security. PMID- 22074351 TI - The role of targeted chemical proteomics in pharmacology. AB - Traditionally, proteomics is the high-throughput characterization of the global complement of proteins in a biological system using cutting-edge technologies (robotics and mass spectrometry) and bioinformatics tools (Internet-based search engines and databases). As the field of proteomics has matured, a diverse range of strategies have evolved to answer specific problems. Chemical proteomics is one such direction that provides the means to enrich and detect less abundant proteins (the 'hidden' proteome) from complex mixtures of wide dynamic range (the 'deep' proteome). In pharmacology, chemical proteomics has been utilized to determine the specificity of drugs and their analogues, for anticipated known targets, only to discover other proteins that bind and could account for side effects observed in preclinical and clinical trials. As a consequence, chemical proteomics provides a valuable accessory in refinement of second- and third generation drug design for treatment of many diseases. However, determining definitive affinity capture of proteins by a drug immobilized on soft gel chromatography matrices has highlighted some of the challenges that remain to be addressed. Examples of the different strategies that have emerged using well established drugs against pharmaceutically important enzymes, such as protein kinases, metalloproteases, PDEs, cytochrome P450s, etc., indicate the potential opportunity to employ chemical proteomics as an early-stage screening approach in the identification of new targets. PMID- 22074353 TI - 'New to Forensic'; implementing a problem-based introductory educational programme for forensic practitioners in Scotland. AB - The New to Forensic educational programme has been developed for use across all forensic services in Scotland. It is designed to meet the needs of all staff who are both new to and already working within forensic mental health services. Its objectives are targeted to both clinical and non-clinical staff. The programme follows the patient's journey through the mental health and criminal justice systems. It covers mental disorder, legislation, psychiatric defences, assessment and treatment, risk of harm to others, services, attitudes and boundaries, multidisciplinary working, users and carers, community, learning disability, and prison services. It is self-directed and practice based, and uses a problem-based approach. Over a 3-year period, trainers and mentors have been trained to deliver the programme by members of the School of Forensic Mental Health http://www.forensicnetwork.scot.nhs.uk/ and all services have adopted the programme as a core educational initiative. Initial findings from the programme evaluation indicate a significant improvement in learning following engagement in the initiative. PMID- 22074352 TI - Toward in vivo imaging of heart disease using a radiolabeled single-chain Fv fragment targeting tenascin-C. AB - Antibodies specific to a particular target molecule can be used as analytical reagents, not only for in vitro immunoassays but also for noninvasive in vivo imaging, e.g., immunoscintigraphies. In the latter case, it is important to reduce the size of antibody molecules in order to achieve suitable in vivo "diagnostic kinetics" and generate higher-resolution images. For these purposes, single-chain Fv fragments (scFvs; M(r) < 30 kDa) have greater potential than intact immunoglobulins (~150 kDa) or Fab (or Fab') fragments (~50 kDa). Our recent observation of enhanced tenascin-C (Tnc) expression at sites of cardiac repair after myocardial infarction prompted us to develop a radiolabeled scFv against Tnc for in vivo imaging of heart disease. We cloned the genes encoding the heavy and light chain variable domains of the mouse anti-Tnc monoclonal antibody 4F10, and combined them to create a single gene. The resulting scFv-4F10 gene was expressed in E. coli cells to produce soluble scFv proteins. scFv-4F10 has an affinity for Tnc (K(a) = 3.5 * 10(7) M(-1)), similar to the Fab fragment of antibody 4F10 (K(a) = 1.3 * 10(7) M(-1)) and high enough to be of practical use. A cysteine residue was then added to the C-terminus to achieve site-specific (111)In labeling via a chelating group. The resulting (111)In-labeled scFv was administered to a rat model of acute myocardial infarction. Biodistribution and quantitative autoradiographic studies indicated higher uptake of the radioactivity at the infarcted myocardium than the noninfarcted one. Single photon emission computed tomography (SPECT) provided in vivo cardiac images that coincided with the ex vivo observations. Our results will promote advances in diagnostic strategies for heart disease. PMID- 22074354 TI - Heel-ball (HB) index: sexual dimorphism of a new index from foot dimensions. AB - The present research is aimed to introduce Heel-ball (HB) index from foot dimensions and determine whether this index exhibits sexual dimorphism. The study was conducted on a sample of 303 North Indian individuals (154 men, and 149 women) aged between 13 and 18 years. The stature, body weight, foot breadth at the ball (BBAL), and foot breadth at heel (BHEL) were measured. The HB index was derived by the formula BHEL * 100/BBAL. Although the mean HB index was larger in women in both feet it showed statistically significant sex differences in the right foot only. The study shows that while the foot dimensions show a positive correlation with stature and weight, the HB index is independent of the stature and weight of an individual. This novel index (HB index) may be utilized in sex determination when a part of the foot is brought for medico-legal investigation. PMID- 22074355 TI - Posture influences patient cough rate, sedative requirement and comfort during bronchoscopy: An observational cohort study. AB - OBJECTIVES: To investigate differences between semi-recumbent and supine postures in terms of cough rate, oxygen desaturation, sedative use, and patient comfort during the initial phase of bronchoscopy. METHODS: Consecutive bronchoscopy patients (n = 69) participated in this observational cohort study. Posture was determined by the bronchoscopist's usual practice. Patient demographics, spirometry, pulse, and SpO2 were recorded. The initial phase was defined as the time from bronchoscopy insertion to visualisation of both distal main bronchi. Cough rate, peak pulse, nadir SpO2, oxygen supplementation, and sedative use during the initial phase were recorded. A post-procedure questionnaire was administered to the patient and the attending nurse. RESULTS: 36 patients had bronchoscopy in the semi-recumbent posture, 33 in the supine posture. 3 of 5 bronchoscopists performed in both postures. There were no differences in baseline parameters between the groups. The semi-recumbent posture resulted in significantly less cough (mean (SD) 3.6 (2.3) vs. 6.1 (4.5) coughs/min, p = 0.007) and less fentanyl use (70 (29) vs. 88 (28) mcg, p = 0.011) in the initial phase. There were no significant differences in the nadir SpO2, fall in SpO2, oxygen supplementation, or increase in pulse rate between the groups. On 100 mm visual analogue scale, nurse perception of patient discomfort was lower in the semi-recumbent position (23 (21) vs. 39 (28) mm, p = 0.01), and there was a trend towards less patient perceived cough in the semi-recumbent group (28 (25) vs. 40 (28) mm, p = 0.06). CONCLUSIONS: Bronchoscopy performed in the semi-recumbent posture results in less cough and sedative requirement, and may improve patient comfort. PMID- 22074356 TI - Duane retraction syndrome: series of 441 cases. AB - PURPOSE: To determine the demographic and clinical profile of various subtypes of Duane retraction syndrome (DRS). METHODS: Retrospective case series of 441 patients. RESULTS: Of the total 441 patients, 389 (88.2%) and 52 (11.8%) patients had unilateral and bilateral involvement, respectively. In both unilateral and bilateral cases, type I was the most common subtype, followed by types III and II. Mean age of presentation of type I DRS was significantly less (13.3 years) compared with types II (23 years) and III (21.9 years) (P < .05). Unilateral disease was significantly more common in females (57. 6%, P = .006), whereas there was no gender predilection in bilateral cases (P = .77). Type 1 DRS was significantly more common among females (57.96%, P = .003) compared with males, whereas there was no such gender predilection in types II and III. The left eye was more commonly involved in patients with types I and III (P < .05), whereas in type II there was no such predilection for any eye involvement. Esotropia was more common in patients with bilateral disease (53.8%) and exotropia was predominant ocular deviation in patients with types II and III (70% and 66.67%, P = .03). There was no difference in the type of deviation in patients with type I (P > .05). Upshoots and downshoots were more common in unilateral disease and types I and III compared with type II. CONCLUSION: Unilateral and bilateral DRS show considerable differences in gender distribution, associated ocular deviation, overshoots, and ocular and systemic associations. PMID- 22074357 TI - Topical ophthalmic moxifloxacin elicits minimal or no selection of fluoroquinolone resistance among bacteria isolated from the skin, nose, and throat. AB - PURPOSE: To investigate whether moxifloxacin therapy of bacterial conjunctivitis in children changes the moxifloxacin susceptibility of bacterial isolates in eyes, cheeks below eyes, nares, and throat. METHODS: Patients (age: 1 to 12 years, n = 105) with bacterial conjunctivitis were treated topically with moxifloxacin three times a day for 7 days. Gender- and age-matched subjects with normal eyes (age: 1 to 12 years, n = 57) served as the control group. Microbiological specimens were collected on days 1 (prior to therapy), 8 (1 day after end of therapy), and 42 (follow-up). Specimens were processed to recover total bacteria and bacteria that grew on fluoroquinolone-selective media. Bacteria were identified to the species level and susceptibility to moxifloxacin and selected other antibiotics determined. RESULTS: The primary pathogens recovered from the infected eyes on day 1 before therapy were Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. None of the pre therapy isolates of H. influenzae and S. pneumoniae were resistant to moxifloxacin. Isolates of these two pathogenic species were also recovered primarily from the nose and eyes. Moxifloxacin-resistant S. aureus isolates (minimum inhibitory concentration 1.0 MUg/mL or greater) were recovered from the nose and throat prior to topical dosing on day 1. However, there was no change in the frequency of moxifloxacin-resistant isolates of S. aureus following treatment with moxifloxacin. CONCLUSION: Treatment of conjunctivitis with topical ophthalmic moxifloxacin did not select for moxifloxacin resistance in H. influenzae, S. pneumoniae, or S. aureus in the eye or distal body sites. PMID- 22074358 TI - Reading skills in children and adults with albinism: the role of visual impairment. AB - PURPOSE: To evaluate whether visual impairment in albinism contributes significantly to the acquisition of normal reading skills. METHODS: The authors administered standardized reading tests to 41 children and 18 adults with albinism. The Young Children's Achievement Test was used for children between 4 and 6 years old and the Woodcock-Johnson III was used for children 7 years and older and adults. Parents of children and adult subjects also completed a questionnaire to document developmental, academic, and/or work experiences. The Spearman test was used to evaluate the relationship between binocular best corrected visual acuity (BCVA) and reading test results. RESULTS: Standardized reading tests in both children and adults with albinism showed a normal distribution of scores. BCVA did not appear to play a significant role in the development of normal reading ability in these individuals who were visually impaired except for a mild correlation of decreased reading fluency on the Woodcock-Johnson III with decreased BCVA (r = 0.287, P = .046). Many young children with albinism had superior reading skills despite having a BCVA of 20/200 or worse (legal blindness). CONCLUSION: This study of cognitively normal children and adults with albinism demonstrates that impaired vision during childhood does not by itself significantly impede a child's ability to acquire normal reading skills. However, the lower reading fluency that occurs in the more visually impaired individuals suggests they would benefit, both in the school system and workplace, with an accommodation involving more time to complete reading tasks. PMID- 22074359 TI - Smooth-pursuit changes after the tenotomy and reattachment procedure for infantile nystagmus syndrome: model predictions and patient data. AB - PURPOSE: Patients with infantile nystagmus syndrome (INS) often cannot quickly locate new visual targets or track moving objects. Dynamic demands on visual function are not measured by static measures (eg, visual acuity); they require time-sensitive measures. The authors investigated how dynamic properties of INS (pursuit-target acquisition times) were affected by the tenotomy and reattachment (T&R) procedure in both patients with INS and behavioral ocular motor system model predictions. METHODS: Responses of 3 patients with different INS waveforms were compared before and after T&R to test the model's predictions. A high-speed digital video system was used to take eye-movement data. Human responses to target-ramp stimuli were analyzed. RESULTS: T&R did not improve the smooth pursuit responses of patients with INS; pursuit-target acquisition times did not show marked improvements. However, in one case, T&R allowed the patient to pursue targets "faster" in a specific direction. CONCLUSION: T&R can improve peak visual acuity, broaden the high-acuity gaze-angle range, and reduce target acquisition times to static targets but not moving targets. When the target moves simultaneously with an ongoing saccade in the nystagmus cycle, the steady-state errors and elongated target acquisition times observed might be part of the intrinsic characteristics of normal pursuit responses. PMID- 22074360 TI - Mesenchymal stem cells prime proliferating adult neural progenitors toward an oligodendrocyte fate. AB - Oligodendrogenesis encompasses lineage specification of neural progenitor cells (NPCs) and differentiation into oligodendrocytes that ultimately culminates in the myelination of central nervous system axons. Each individual process must be tightly regulated by extracellular and cell-intrinsic mechanisms, whose identities are barely understood. We had previously demonstrated that soluble factors derived from rat mesenchymal stem cells (MSCs) induce oligodendrogenesis in differentiating adult NPCs under differentiation conditions. However, since lineage specification predominantly occurs in proliferating progenitors and not necessarily during early differentiation, we investigated if soluble factors derived from MSCs are able to prime NPCs to the oligodendroglial fate already under proliferation conditions. Therefore, we analyzed the effects of a 3 weeks stimulation of adult NPCs under proliferation conditions with conditioned media derived from MSCs (MSC-CM) in terms of cell morphology, proliferation, cell specific marker expression profile, response to growth factor withdrawal (GFW), cell-lineage restriction, and expression of glial fate determinants. While MSC-CM did not affect the proliferation rate of NPCs, it boosted the formation of 2', 3' cyclic-nucleotide-3'-phosphodieesterase (CNPase)- and myelin basic protein expressing oligodendrocytes after GFW, even when cells were exposed to an astrogenic milieu. Moreover, it reinforced the proper development of oligodendrocytes, since it ensured a sustained expression of the functional marker CNPase. Finally, the presence of MSC-CM reduced the anti-oligodendrogenic determinant Id2 in proliferating NPCs, thus increasing the relative proportion of the pro-oligodendrogenic factor Olig2 expression. In summary, MSCs prime proliferating progenitors and, thus, reinforce cell fate choice and accelerate differentiation toward the oligodendrocyte lineage. The present findings underscore the potential use of MSCs in cell therapies for remyelination such as in multiple sclerosis and spinal cord injury. Moreover, they urge the identification of the oligodendrogenic activity(ies) derived from MSCs to develop novel molecular therapies for demyelinating diseases. PMID- 22074361 TI - Animal fibre: the forgotten nutrient in strict carnivores? First insights in the cheetah. AB - As wild felids are obligate carnivores, it is likely that poorly enzymatically digestible animal tissues determine hindgut fermentation, instead of plant fibre. Therefore, faecal concentrations of short-chain fatty acids (SCFA, including branched-chain fatty acids, BCFA), indole and phenol were evaluated in 14 captive cheetahs, fed two different diets differing in proportion of poorly enzymatically digestible animal tissue. Using a cross-over design, the cheetahs were fed exclusively whole rabbit or supplemented beef for 1 month each. Feeding whole rabbit decreased faecal propionic (p < 0.001) and butyric (p = 0.013) acid concentrations, yet total SCFA was unaltered (p = 0.146). Also, a remarkably higher acetic acid to propionic acid ratio (p = 0.013) was present when fed whole rabbit. Total BCFA (p = 0.011) and putrefactive indole (p = 0.004) and phenol (p = 0.002) were lower when fed whole rabbit. Additionally, serum indoxyl sulphate, a toxic metabolite of indole, was analysed and showed a quadratic decrease (p = 0.050) when fed whole rabbit. The divergent SCFA ratios and the decrease in putrefaction when fed whole rabbit could be caused by the presence of undigested tissue, such as skin, bone and cartilage, that might have fibre-like functions. The concept of animal fibre is an unexplored area of interest relevant to gastrointestinal health of captive cheetahs and likely other felids. PMID- 22074362 TI - A novel actin-microtubule cross-linking kinesin, NtKCH, functions in cell expansion and division. AB - * Kinesins with a calponin homology domain (KCHs) have been identified recently as a plant-specific subgroup of the kinesin-14 family and are suspected to act as microtubule-actin filament cross-linkers. The cellular function, however, has remained elusive. * In order to address the function of KCHs, we isolated NtKCH, a novel KCH homologue from tobacco BY-2 cells. Following synchronization, NtKCH transcripts were shown to be abundant during mitosis, whereas, during interphase, expression was low. * Using fluorescent-tagged cell lines and immunolabelling techniques, the localization of tobacco KCH was found to differ depending on the cell cycle. During interphase, NtKCH mainly associated with cortical microtubules, whereas a subfraction also co-localized with perinuclear actin cables. In dividing cells, NtKCH accumulated at the pre-prophase band and at the phragmoplast. However, it remained absent from spindle microtubules, but, instead, concentrated at two agglomerations in proximity to the two cell poles. * This work develops a detailed model for the dual localization and function of NtKCH during cell division vs cell expansion. This model implies two dynamic states of KCHs that differ with regard to actin interaction. This allows the modulation of force generation by KCH in a cell cycle-dependent capture mechanism. PMID- 22074363 TI - Light-induced copper(II) coordination by a bicyclic tetraaza chelator through a ligand-to-metal charge-transfer reaction. AB - To enable utilization of the broad potential of copper isotopes in nuclear medicine, rapid and robust chelation of the copper is required. Bowl adamanzanes (bicyclic tetraaza ligands) can form kinetically stable copper complexes, but they are usually formed at low rates unless high pH values and high temperatures are applied. We have investigated the effects of the variation in the pH, different anions, and UV irradiation on the chelation rate. UV spectra of mixtures of Cu(2+) and [2(4).3(1)]adz in water show the existence of a long-lived two-coordinated copper(II) intermediate (only counting coordinated amine groups) at pH above 6. These findings are supported by pH titrations of mixtures of Cu(2+) and [2(4).3(1)]adz in water. Irradiation of this complex in the ligand-to metal charge-transfer (LMCT) band by a diode-array spectrophotometer leads to photodeprotonation and subsequently to formation of the four-coordinated copper(II) complex at a rate up to 7800-fold higher at 25 degrees C than in the dark. Anions in the solution were found to have three major effects: competitive inhibition due to Cu(II) binding anions, inhibition of the photoinduced transchelation from UV-absorbing anions, and photoredox inhibition from acido ligands capable of acting as electron donors in LMCT reactions. Dissolved O(2) was also found to result in photoredox inhibition. PMID- 22074364 TI - Myoendothelial contacts, gap junctions, and microdomains: anatomical links to function? AB - In several species and in many vascular beds, ultrastructural studies describe close contact sites between the endothelium and smooth muscle of <~20nm. Such sites are thought to facilitate the local action of signaling molecules and/or the passage of current, as metabolic and electrical coupling conduits between the arterial endothelium and smooth muscle. These sites have the potential for bidirectional communication between the endothelium and smooth muscle, as a key pathway for coordinating vascular function. The aim of this brief review is to summarize the literature on the ultrastructural anatomy and distribution of key components of MECC sites in arteries. In addition to their traditional role of facilitating electrical coupling between the two cell layers, data on the role of MECC sites in arteries, as signaling microdomains involving a spatial localization of channels, receptors and calcium stores are highlighted. Diversity in the density and specific characteristics of MECC sites as signaling microdomains suggests considerable potential for functional diversity within and between arteries in health and disease. PMID- 22074365 TI - Hormonal response to lipid and carbohydrate meals during the acute postprandial period. AB - BACKGROUND: Optimizing the hormonal environment during the postprandial period in favor of increased anabolism is of interest to many active individuals. Data are conflicting regarding the acute hormonal response to high fat and high carbohydrate feedings. Moreover, to our knowledge, no studies have compared the acute hormonal response to ingestion of lipid and carbohydrate meals of different size. METHODS: We compared the hormonal response to lipid and carbohydrate meals of different caloric content during the acute postprandial period. Nine healthy men (22 +/- 2 years) consumed in a random order, cross-over design one of four meals/beverages during the morning hours in a rested and fasted state: dextrose at 75 g (300 kcals), dextrose at 150 g (600 kcals), lipid at 33 g (300 kcals), lipid at 66 g (600 kcals). Blood samples were collected Pre meal, and at 0.5 hr, 1 hr, 2 hr, and 3 hr post meal. Samples were assayed for testosterone, cortisol, and insulin using ELISA techniques. Area under the curve (AUC) was calculated for each variable, and a 4 * 5 ANOVA was used to further analyze data. RESULTS: A meal * time effect (p = 0.0003) was noted for insulin, with values highest for the dextrose meals at the 0.5 hr and 1 hr times, and relatively unaffected by the lipid meals. No interaction (p = 0.98) or meal (p = 0.39) effect was noted for testosterone, nor was an interaction (p = 0.99) or meal (p = 0.65) effect noted for cortisol. However, a time effect was noted for both testosterone (p = 0.04) and cortisol (p < 0.0001), with values decreasing during the postprandial period. An AUC effect was noted for insulin (p = 0.001), with values higher for the dextrose meals compared to the lipid meals (p < 0.05). No AUC effect was noted for testosterone (p = 0.85) or cortisol (p = 0.84). CONCLUSIONS: These data indicate that 1) little difference is noted in serum testosterone or cortisol during the acute postprandial period when healthy men consume lipid and dextrose meals of different size; 2) Both testosterone and cortisol experience a drop during the acute postprandial period, which is similar to what is expected based on the normal diurnal variation--feeding with lipid or dextrose meals does not appear to alter this pattern; 3) dextrose meals of either 75 g or 150 g result in a significant increase in serum insulin, in particular at 0.5 hr and 1 hr post ingestion; 4) lipid meals have little impact on serum insulin. PMID- 22074366 TI - Etanercept: efficacy and safety for approved indications. AB - INTRODUCTION: Etanercept is a tumor necrosis factor alpha (TNF-alpha) inhibitor, which is approved for the treatment of immune-mediated inflammatory conditions including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and psoriasis (PsO). AREAS COVERED: Clinical efficacy and safety data of etanercept for the approved indications are reviewed in this paper. Data were obtained from published clinical trials, registries, post-marketing data as well as information provided by Amgen. EXPERT OPINION: Etanercept is a generally well-tolerated treatment for the approved inflammatory diseases. The most common adverse effect of etanercept treatment is injection site reaction, which is generally self-limiting and often does not require treatment. Etanercept may be associated with an increased risk for infection, the development of malignancy, demyelinating disease and congestive heart failure. Fewer patients withdraw from etanercept due to adverse events than with other biologics. For pediatric patients, there are more data for etanercept than other biologics, and etanercept may have lower rates for the development of malignancy. PMID- 22074367 TI - Prevalence and factors associated with traditional herbal medicine use among patients on highly active antiretroviral therapy in Uganda. AB - BACKGROUND: In Africa, herbal medicines are often used as primary treatment for Human immunodeficiency virus (HIV) related problems. Concurrent use of traditional herbal medicines (THM) with antiretroviral drugs (ARVs) is widespread among HIV infected patients. However, the extent of THM use is not known in most settings in Sub-Saharan Africa. This study aimed at determining the prevalence and factors associated with THM use among HIV infected patients on highly active antiretroviral therapy (HAART) attending The AIDS Support Organization (TASO) in Uganda. TASO is a non-governmental organization devoted to offering HIV/AIDS care and treatment services in the population. METHODS: This was a cross-sectional study carried out in two TASO treatment centres in Uganda among 401 randomly selected eligible participants. We included participants who were 18 years and above, were enrolled on HAART, and consented to participate in the study. Data was collected using an interviewer-administered semi-structured questionnaire. THM use referred to someone who had ever used or was currently using herbal medicine while on highly active antiretroviral therapy (HAART) by the time of the study. Data was captured in Epi-data version 3.1 and exported to STATA version 9.0 for analysis. RESULTS: The prevalence of THM use was 33.7%. Patients on HAART for < 4 years were more likely to use THM (OR = 5.98, 95% CI 1.13 - 31.73) as well as those who experienced HAART side effects (OR = 3.66, 95% CI: 1.15 - 11.68). Older patients (>=39 years) were less likely to use THM (OR = 0.26 95% CI: 0.08 - 0.83). Participants with HAART adherence levels > 95% were less likely to use THM (OR = 0.09, 95% CI 0.01 - 0.65). CONCLUSION: The prevalence of THM use among participants on HAART was high. This raises clinical and pharmacological concerns that need attention by the health care service providers. PMID- 22074368 TI - Infancy- and childhood-onset dyschromatoses. AB - The dyschromatoses are a group of pigmentary disorders characterized clinically by mixed and often guttate hypopigmented and hyperpigmented lesions. There are many conditions that present with dyschromatosis, including genodermatoses, inflammatory skin diseases, infections, drug and chemical use, and nutritional disorders. Some conditions have extracutaneous features. Poikiloderma (a combination of hypo- and hyperpigmentation with telangiectasia and atrophy) must be excluded. In this article, we describe the dyschromatoses typically presenting in infancy and childhood, most of which are genodermatoses. The approach we have taken in classifying them is based on organ involvement. We hope this article will serve as a guide for dermatologists to the recognition of these uncommon conditions. PMID- 22074369 TI - What's new in acne? An analysis of systematic reviews and clinically significant trials published in 2010-11. AB - This review summarizes important clinical developments in acne treatment identified in five systematic reviews and two significant primary research studies, published between March 2010 and February 2011. Although evidence showing a direct link between development of bacterial resistance and oral antibiotic therapy for acne is not convincing, prescribers can still tailor their practice to minimize future risks by stopping treatment when appropriate, using benzoyl peroxide, and avoiding combining topical and systemic antimicrobials. A systematic review evaluating combination products containing benzoyl peroxide did not show convincing evidence that such products are superior to monotherapies. A systematic review of combined oral contraceptives confirmed their efficacy for acne in women. However, another systematic review of botanical products for acne failed to provide any good-quality evidence of benefit. A large, well-reported retrospective cohort study attempted to clarify the potential link between isotretinoin and depression/suicide. Although suicide risk peaked 6 months after isotretinoin treatment, an increased risk was present before initiation of isotretinoin, making it difficult to attribute the increased risk to isotretinoin alone. However, those with a history of suicide attempts before treatment made fewer new attempts than those whose behaviour started during treatment. This suggests that patients with severe acne with a history of attempted suicide should not automatically be refused isotretinoin. Another randomized controlled trial of 60 patients from Korea suggested that low-dose isotretinoin dose than might provide a better long-term outcome with minimal side-effects for people with moderate acne. PMID- 22074370 TI - Basal cell carcinoma masquerading as habit tic. PMID- 22074371 TI - Asymptomatic vulvar pigmentation. PMID- 22074372 TI - I have spikes on my hands. PMID- 22074373 TI - Giant verrucous lesion on the scalp. PMID- 22074374 TI - Interventions for pemphigus vulgaris and pemphigus foliaceus: a summarised Cochrane review. PMID- 22074375 TI - Topical treatments for chronic plaque psoriasis: a summarised Cochrane review. PMID- 22074376 TI - Molecular markers to characterize the hermaphroditic reproductive system of the planarian Schmidtea mediterranea. AB - BACKGROUND: The freshwater planarian Schmidtea mediterranea exhibits two distinct reproductive modes. Individuals of the sexual strain are cross-fertilizing hermaphrodites with reproductive organs that develop post-embryonically. By contrast, individuals of the asexual strain reproduce exclusively by transverse fission and fail to develop reproductive organs. These different reproductive strains are associated with distinct karyotypes, making S. mediterranea a useful model for studying germline development and sexual differentiation. RESULTS: To identify genes expressed differentially between these strains, we performed microarray analyses and identified >800 genes that were upregulated in the sexual planarian. From these, we characterized 24 genes by fluorescent in situ hybridization (FISH), revealing their expression in male germ cells or accessory reproductive organs. To identify additional markers of the planarian reproductive system, we also used immuno- and fluorescent lectin staining, identifying several antibodies and lectins that labeled structures associated with reproductive organs. CONCLUSIONS: Collectively, these cell-type specific markers will enable future efforts to characterize genes that are important for reproductive development in the planarian. PMID- 22074377 TI - A systematic assessment of the concept and practice of public-private mix for tuberculosis care and control. AB - INTRODUCTION: The STOP TB Partnership aims to improve global tuberculosis (TB) control through expanding access to the directly observed treatment short course (DOTS) strategy. One approach to this is 'Engaging all Care Providers', which evolved from 'Public-Private Mix (PPM) DOTS'. The overall aim of this study was to systematically assess whether and to what degree the STOP TB Partnership's four global objectives of engaging all care providers are met through existing PPM interventions. These four objectives are; 1) Increase TB case detection; 2) Improve TB treatment outcomes; 3) Enhance access and equity; 4) Reduce financial burden on patients. The specific objectives of this assessment were to 1) Understand what PPM means to the STOP TB Partnership's PPM Subgroup and to National Tuberculosis Programme managers; 2) Scope the nature of existing country level PPM interventions and 3) Review PPM practice against the global PPM objectives. METHODS: We undertook a systematic, multi-facetted assessment. The methods included interviews with National Tuberculosis Programme managers from high burden countries, clarification of key issues with the STOP TB Partnership PPM secretariat and a review of publicly accessible reports and published articles on PPM projects. Both the literature review and interviews with the National Tuberculosis Programme managers yielded data on project characteristics; PPM models at country level; National Tuberculosis Programme partners; and mechanisms for engagement. Matrices were developed from the literature review and the interviews to show the relationship between services and service providers for different PPM projects. Data from the literature were assessed against each of the four global PPM objectives. RESULTS: Twelve National Tuberculosis Programme managers from high burden countries were interviewed about the scope of PPM partnerships. Understanding of PPM and types of engaged providers varied considerably; 'private-for-profit qualified clinical providers' were the dominant category. The literature review yielded information on 22 projects in which 'private-for-profit qualified clinical providers' were again the dominant category. The contributions made by 'private-for-profit qualified clinical providers' and 'Non Governmental Organisation qualified clinical providers', were assessed against the four global PPM objectives. Reporting on tuberculosis case detection and treatment outcomes was generally good and demonstrated important PPM contributions in these areas. Reporting on equity, access and reduced patient costs was often lacking or inconclusive. CONCLUSIONS: PPM has improved case detection and treatment outcomes among patients seeking care with private providers. Evidence on reducing patient costs is inconclusive, and there is scope for increasing equity in access to care by systematically engaging those providers who are the primary agents for poor people seeking health care. Guidelines outlining which types of providers best contribute to achieving the four global objectives, along with the resources required by National Tuberculosis Programs for such engagement is needed. PMID- 22074378 TI - A predictive biomimetic model of cytokine release induced by TGN1412 and other therapeutic monoclonal antibodies. AB - Human peripheral blood mononuclear cells (PBMC) are routinely used in vitro to detect cytokine secretion as part of preclinical screens to delineate agonistic and antagonistic action of therapeutic monoclonal antibodies (mAbs). Preclinical value of standard human PBMC assays to detect cytokine release syndrome (CRS) has been questioned, as they did not predict the "cytokine storm" that occurred when healthy human volunteers were given a CD28-specific super-agonist mAb, TGN1412. In this article, we describe a three-dimensional biomimetic vascular test-bed that can be used as a more physiologically relevant assay for testing therapeutic Abs. For developing such a system, we used TGN1412 as a model mAb. We tested soluble TGN1412 on various combinations of human blood components in a module containing endothelial cells grown on a collagen scaffold and measured cytokine release using multiplex array. Our system, consisting of whole leukocytes, endothelial cells, and 100% autologous platelet-poor plasma (PPP) consistently produced proinflammatory cytokines in response to soluble TGN1412. In addition, other mAb therapeutics known to induce CRS or first infusion reactions, such as OKT3, Campath-1H, or Herceptin, generated cytokine profiles in our model system consistent with their in vivo responses. As a negative control we tested the non CRS mAbs Avastin and Remicade and found little difference between these mAbs and the placebo control. Our data indicate that this novel assay may have preclinical value for predicting the potential of CRS for mAb therapeutics. PMID- 22074379 TI - Preface to the special issue "Novel pharmaconeurogenetic approaches arising from progress in translational genetics". PMID- 22074380 TI - FRep: a fluorescent protein-based bioprobe for in vivo detection of protein-DNA interactions. AB - We describe a bacterial reporter system, FRep, for rapid and facile detection of protein-DNA recognition. The bioprobe reporter comprises genes of two fluorescent proteins (FPs) separated by a potential DNA target. If a coexpressed transcription factor binds the DNA target, transcription of the second FP is impeded, resulting in loss of FRET partner. Using ratiometric FRET, we show that evaluation of protein-DNA recognition can be reliably made on bZIP and bHLHZ transcription factors and their DNA targets. FRep displays similar thresholds of detection regarding protein-DNA binding affinities, as compared to well established electrophoretic and yeast assays, although we observed variations in the intensity of fluorescence signals and detection thresholds that may depend on differences between DNA-binding protein production levels and/or stability in the cell, or the expressed bioprobe linker between the two FPs. FRep can potentially be applied to high-throughput searches of both protein and DNA libraries; in a mock library screen, binding and nonbinding complexes can even be distinguished by visual inspection of colonies on plates. FRep presents notable advantages over existing technologies when applied to assessing protein-DNA interactions in vivo, and this approach has the potential for applications in assaying protein-protein interactions and screening molecules that influence specific macromolecular interactions. PMID- 22074381 TI - Learning from the 2011 Great East Japan Disaster: insights from a special radiological emergency assistance mission. AB - On March 11, 2011, the eastern portion of Japan was struck by a massive earthquake and tsunami that killed more than 15,700 people, left thousands of others hurt or missing, and caused widespread destruction. In addition, the Great East Japan Disaster seriously damaged the Fukushima Dai-ichi nuclear power station, knocking out power, severely affecting communications, and causing a loss of cooling to some reactor cores. Significant quantities of radioactive materials were released, a "no go" zone was created around the crippled reactors, and thousands of people were evacuated. With concern about the radiological emergency growing, one of Japan's largest hospital and healthcare groups issued a request for assistance to a U.S.-based international disaster relief organization. After consultations with the Japanese, a special Radiological Emergency Assistance Mission was assembled. The mission, which traveled to Japan in April 2011, had several aims: (1) to rapidly assess the situation on the ground, (2) to exchange information, experiences, and insights with Japanese colleagues, and (3) to provide radiological information and practical refresher training to Japanese healthcare professionals and first responders. In addition to achieving these aims and laying the groundwork for future cooperation, the mission produced dozens of insights and lessons. These have potential relevance not only for future large-scale radiation accidents, but also for radiological and nuclear terrorism situations. They also have more general relevance for emergency planning, preparedness, and response. In this article, several of the most salient insights and lessons are highlighted. PMID- 22074383 TI - Flowering phenology as a functional trait in a tallgrass prairie. AB - * The timing of flowering is a critical component of the ecology of plants and has the potential to structure plant communities. Yet, we know little about how the timing of flowering relates to other functional traits, species abundance, and average environmental conditions. * Here, we assessed first flowering dates (FFDs) in a North American tallgrass prairie (Konza Prairie) for 431 herbaceous species and compared them with a series of other functional traits, environmental metrics, and species abundance across ecological contrasts. * The pattern of FFDs among the species of the Konza grassland was shaped by local climate, can be linked to resource use by species, and patterns of species abundance across the landscape. Peak FFD for the community occurred when soils were typically both warm and wet, while relatively few species began flowering when soils tended to be the driest. Compared with late-flowering species, species that flowered early had lower leaf tissue density and were more abundant on uplands than lowlands. * Flowering phenology can contribute to the structuring of grassland communities, but was largely independent of most functional traits. Therefore, selection for flowering phenology may be independent of general resource strategies. PMID- 22074382 TI - A novel GABA(A) receptor pharmacology: drugs interacting with the alpha(+) beta( ) interface. AB - GABA(A) receptors are ligand-gated chloride channels composed of five subunits that can belong to different subunit classes. The existence of 19 different subunits gives rise to a multiplicity of GABA(A) receptor subtypes with distinct subunit composition; regional, cellular and subcellular distribution; and pharmacology. Most of these receptors are composed of two alpha, two beta and one gamma2 subunits. GABA(A) receptors are the site of action of a variety of pharmacologically and clinically important drugs, such as benzodiazepines, barbiturates, neuroactive steroids, anaesthetics and convulsants. Whereas GABA acts at the two extracellular beta(+) alpha(-) interfaces of GABA(A) receptors, the allosteric modulatory benzodiazepines interact with the extracellular alpha(+) gamma2(-) interface. In contrast, barbiturates, neuroactive steroids and anaesthetics seem to interact with solvent accessible pockets in the transmembrane domain. Several benzodiazepine site ligands have been identified that selectively interact with GABA(A) receptor subtypes containing alpha2betagamma2, alpha3betagamma2 or alpha5betagamma2 subunits. This indicates that the different alpha subunit types present in these receptors convey sufficient structural differences to the benzodiazepine binding site to allow specific interaction with certain benzodiazepine site ligands. Recently, a novel drug binding site was identified at the alpha(+) beta(-) interface. This binding site is homologous to the benzodiazepine binding site at the alpha(+) gamma2(-) interface and is thus also strongly influenced by the type of alpha subunit present in the receptor. Drugs interacting with this binding site cannot directly activate but only allosterically modulate GABA(A) receptors. The possible importance of such drugs addressing a spectrum of receptor subtypes completely different from that of benzodiazepines is discussed. PMID- 22074384 TI - Colloidal structure and stability of DNA/polycations polyplexes investigated by small angle scattering. AB - Polyplexes of short DNA-fragments (300 b.p., 100 nm) with tailor-made amine-based polycations of different architectures (linear and hyperbranched) were investigated in buffer solution as a function of the mixing ratio with DNA. The resulting dispersed polyplexes were characterized using small-angle neutron and X ray scattering (SANS, SAXS) as well as cryo-TEM with respect to their mesoscopic structure and their colloidal stability. The linear polyimines form rather compact structures that have a high tendency for precipitation. In contrast, the hyperbranched polycation with enzymatic-labile pentaethylenehexamine arms (PEHA) yields polyplexes colloidally stable for months. Here the polycation coating of DNA results in a homogeneous dispersion based on a fractal network with low structural organization at low polycation amount. With increasing polycation, bundles of tens of aligned DNA rods appear that are interconnected in a fractal network with a typical correlation distance on the order of 100 nm, the average length of the DNA used. With higher organization comes a decrease in stability. The 3D network built by these beams can still exhibit some stability as long as the material concentration is large enough, but the structure collapses upon dilution. SAXS shows that the complexation does not affect the local DNA structure. Interestingly, the structural findings on the DNA polyplexes apparently correlate with the transfection efficiency of corresponding siRNA complexes. In general, these finding not only show systematic trends for the colloid stability, but may allow for rational approaches to design effective transfection carriers. PMID- 22074385 TI - Effect of stress on hippocampal nociceptin expression in the rat. AB - Nociceptin/orphanin FQ (N/OFQ) peptide and its receptor are not only ubiquitously expressed in mammalian brain and spinal cord but are also abundant in limbic structures, particularly in the hippocampus. The widespread distribution of N/OFQ reflects the broad spectrum of its biological actions such as nociception, food intake, spontaneous locomotor activity, and learning and memory processes. Since the hippocampus is involved in the control of adrenocortical activity, its role in stress-related phenomena is well characterized. In male Wistar rats, we first examined the effects of acute restraint stress (120 min) on the brain immunohistochemical localization of N/OFQ. The analysis carried out on sections obtained at the onset of stress revealed enhanced expression of N/OFQ in CA1, CA3, and the dentate gyrus as well as increased plasma corticosterone concentrations. Next, we examined whether endogenous glucocorticoid hormone plays a role in the modulation of hippocampal N/OFQ expression in response to stress. To this end, rats were injected with corticosterone (1 mg/kg) or subjected to restraint stress 1 week after adrenalectomy. Two hours after corticosterone administration, plasma glucocorticoid concentrations were comparable to those observed after restraint stress, while N/OFQ expression had significantly increased in all the hippocampal subfields examined. By contrast, in adrenalectomized rats, stress did not modify protein expression. These results confirm that stress can affect N/OFQ expression and that glucocorticoids may constitute hormonal mediators of this complex interplay. PMID- 22074386 TI - Longitudinal melanonychia caused by Fusarium oxysporum in immunocompetent patient. PMID- 22074387 TI - Hurler disease (mucopolysaccharidosis type IH): clinical features and consanguinity in Tunisian population. AB - Mucopolysaccharidosis type I (MPS I) was a group of rare autosomal recessive disorder caused by the deficiency of the lysosomal enzyme, alpha -L -iduronidase, and the resulting accumulation of undergraded dematan sulfate and heparan sulfate. MPS I patients have a wide range of clinical presentations, that makes it difficult to predict patient phenotype which is needed for genetic counseling and also impedes the selection and evaluation of patients undergoing therapy bone marrow transplantation. AIM OF THE STUDY: consanguinity rates have been determined among 14 families with mucopolysaccharidosis type I, seen in the pediatric departments of different geographic areas of Tunisia (Central and Southern areas) for the period August 2004 - August 2011 in order to investigate the relation between consanguinity and this disorder. PATIENTS AND METHODS: Clinical and molecular analyses confirmed the diagnosis for MPS type I in the studied families. RESULTS: Most of the Tunisian MPS I patients have been identified at the homozygous status: p.P533R mutation (7 homozygous and one double heterozygous p.L578Q/p.P533R patients; 41.66% of all the investigated MPSI patients), p.F177S (1 homozygous patient; 5.55%), p.L530fs (1 patient; 5.55%), p.Y581X (2 patients; 11.11%), p.F602X (3 patients; 16.66%), p.R628X (1 patient; 5.55%). Another mutation: p.L578Q has been identified at the heterozygous status in the only double heterozygous p.L578Q/p.P533R case. Part of the mutations was the result of a founder effect. These described points are the consequences of the high rate of consanguinity. CONCLUSION: The high frequency of p.P533R mutation could be explained by the high degree of inbreeding. This is due to the richness of the genetic background of the studied population.A multidisciplinary approach is essential to develop adequate preventive program adapted to the social, cultural, and economic context. PMID- 22074388 TI - Napsin A expression in pulmonary sclerosing haemangioma. PMID- 22074389 TI - The absence of MyD88 has no effect on the induction of alternatively activated macrophage during Fasciola hepatica infection. AB - Alternatively activated macrophages (AAMphi) play important roles in allergies and responses toparasitic infections. However, whether signaling through toll like receptors (TLRs) plays any role in AAMphi induction when young Fasciola hepatica penetrates the liver capsule and migrates through the liver tissue is still unclear. RESULTS: The data show that the lack of myeloid differentiation factor 88 (MyD88) has no effect on the AAMphi derived from the bone marrow (BMMphi) in vitro and does not impair the mRNA expression of arginase-1, resistin like molecule (RELMalpha), and Ym1 in BMMphis. The Th2 cytokine production bias in splenocytes was not significantly altered in F. hepatica-infected mice in the absence of MyD88 in vitro and in the pleural cavity lavage in vivo. In addition, MyD88-deficiency has no effect on the arginase production of the F. hepatica elicited macrophages (Fe Mphis), production of RELMalpha and Ym1 proteins and mRNA expression of Ym1 and RELMalpha of macrophages in the peritoneal cavity 6 weeks post F. hepatica infection. CONCLUSIONS: The absence of MyD88 has no effect on presence of AAMphi 6 weeks post F. hepatica infection. PMID- 22074390 TI - Construction of highly functional quaternary carbon stereocenters via an organocatalytic tandem cyanation-allylic alkylation reaction. AB - The first tertiary amine-catalyzed tandem cyanation-allyic alkylation (CAA) reaction of aldehydes, appropriate cyanide sources, and Morita-Baylis-Hillman (MBH) adducts has been developed, which provides a facile access to densely functionalized products containing O-substituted quaternary centers. PMID- 22074391 TI - 'Painting a path to wellness': correlations between participating in a creative activity group and improved measured mental health outcome. AB - Responding to a call for quantitative outcome evidence about the therapeutic relationship between creative activity and mental health, this study examined the mental health outcomes of inpatients participating in art- and craft-based creative therapies at a private psychiatric hospital over a 5-year period. The creative activity group sample (n= 403) improved from admission to discharge across four different psychometric measures with moderate to strong mean effect sizes. Reductions from pre- to post-treatment in both self-reported and clinician rated symptoms are clearly demonstrated for the creative activity group participant sample. Research findings establish that participation in creative activity has potential benefits for people experiencing mental health problems. PMID- 22074392 TI - Air embolus to arachnoid cyst as a rare delayed complication of intrathecal medication delivery. AB - INTRODUCTION: Intrathecal (IT) medication delivery is a commonly used technique for the treatment of chronic intractable pain. Cerebrospinal fluid (CSF) loculation at the catheter tip has been described as a cause of progressive loss of drug effect that can often be difficult to diagnose. METHODS: The clinical course of a 56-year-old woman was reviewed, including past imaging studies. RESULTS: The patient presented with acute lower extremity paresis secondary to air trapped within an arachnoid cyst thought to be due to long-term use of IT morphine and an undiagnosed CSF loculation. She rapidly recovered after surgical decompression. DISCUSSION: Symptomatic pneumorachis is rare. In this case, because of radiographically impressive compression and severe deficit, we felt that the trapped air was equivalent to a mass lesion and treated it aggressively. The arachnoid cyst was near the level of the catheter tip prior to revision, and we have retrospectively inferred a causal relationship. PMID- 22074393 TI - Two-dimensional fourier transform spectroscopy of adenine and uracil using shaped ultrafast laser pulses in the deep UV. AB - We compare two-dimensional (2D) ultrafast Fourier transform spectroscopy measurements in the deep UV (262 nm) for adenine and uracil in solution. Both molecules show excited-state absorption on short time scales and ground-state bleaching extending for over 1 ps. While the 2D spectrum for uracil shows changes in the center of gravity during the first few hundred femtoseconds, the center of gravity of the 2D spectrum for adenine does not show similar changes. We discuss our results in light of ab initio electronic structure calculations. PMID- 22074394 TI - Treatment strategies for childhood noninfectious chronic uveitis: an update. AB - BACKGROUND: Uveitis is an inflammatory disorder involving inflammation of the uveal tract. It is classified as anterior, intermediate, posterior or panuveitis, depending on the part of eye affected by the inflammatory process. In children, noninfectious, chronic uveitis is a relatively uncommon but serious disease, with the potential for significant long-term complications and possible blindness. Although frequently associated with an underlying systemic disease, for example, juvenile idiopathic arthritis, a significant number of cases in children show no associated signs or symptoms and are labeled as idiopathic. RESULTS: We reviewed the available literature. Taking into account this evidence, an anti-inflammatory therapy based on an immunomodulatory approach seems a reasonable strategy for noninfectious chronic uveitis, in children as well as in adults. Due to a lack of controlled studies regarding uveitis in children, immunosuppressive strategy is supported only at evidence level III. Our aim is to review the currently available medical strategies for the treatment of childhood sight-threatening chronic uveitis. CONCLUSION: Uveitis in children can be severe. Methotrexate is the drug of choice for recalcitrant cases, and biologic therapies can be useful in selected situations. PMID- 22074395 TI - High dilution of anionic vacancies in Sr(0.8)Ba(0.2)Fe(O,F)(~2.5). AB - The (Ba,Sr)FeO(3-delta) system is known for its strong tendency for oxygen and vacancies to order into several forms including fully ordered pseudobrownmillerites, hexagonal perovskites with segregation of the vacancies in particular anionic layers and low deficient (pseudo)cubic compounds (generally delta < 0.27, Fe(3/4+)). We show for the first time, using a simple chemical process, the easy access to a large amount of vacancies (delta ~ 0.5, Fe(3+)) within the room-temperature stable tetragonal (pseudocubic) Sr(0.8)Ba(0.2)FeF(~0.1)(O,F)(~2.5.) The drastic effect of the incorporation of a minor amount of fluoride passes through the repartition of local O/F/? constraints shifting the tolerance factor into the pseudocubic range for highly deficient compounds. It is stable up to 670 K, where an irreversible reoxidation process occurs, leading to the cubic-form. The comparison with the cubic oxide Sr(0.8)Ba(0.2)FeO(~2.7) shows the increase of the resistivity (3D-VRH model) by two decades due to the almost single valent Fe(3+) of the oxofluoride. In addition, the G-type magnetic ordering shows relatively weak moment for Fe(3+) cations (M(Fe) ~ 2.64(1) MUB at room temperature) attributed to incoherent magnetic components expected from local disorder in such anionic-deficient compounds. PMID- 22074396 TI - Synthesis and magnetic properties of Zr doped ZnO Nanoparticles. AB - Zr doped ZnO nanoparticles are prepared by the sol-gel method with post annealing. X-ray diffraction results show that all samples are the typical hexagonal wurtzite structure without any other new phase, as well as the Zr atoms have successfully entered into the ZnO lattices instead of forming other lattices. Magnetic measurements indicate that all the doping samples show room temperature ferromagnetism and the pure ZnO is paramagneism. The results of Raman and X-ray photoelectron spectroscopy indicate that there are a lot of oxygen vacancies in the samples by doping element of Zr. It is considered that the observed ferromagnetism is related to the doping induced oxygen vacancies. PMID- 22074397 TI - Biological monitoring of pesticide exposures in residents living near agricultural land. AB - BACKGROUND: There is currently a lack of reliable information on the exposures of residents and bystanders to pesticides in the UK. Previous research has shown that the methods currently used for assessing pesticide exposure for regulatory purposes are appropriate for farm workers 1. However, there were indications that the exposures of bystanders may sometimes be underestimated. The previous study did not collect data for residents. Therefore, this study aims to collect measurements to determine if the current methods and tools are appropriate for assessing pesticide exposure for residents living near agricultural fields. METHODS/DESIGN: The study will recruit owners of farms and orchards (hereafter both will be referred to as farms) that spray their agricultural crops with certain specified pesticides, and which have residential areas in close proximity to these fields. Recruited farms will be asked to provide details of their pesticide usage throughout the spray season. Informed consenting residents (adults (18 years and over) and children (aged 4-12 years)) will be asked to provide urine samples and accompanying activity diaries during the spraying season and in addition for a limited number of weeks before/after the spray season to allow background pesticide metabolite levels to be determined. Selected urine samples will be analysed for the pesticide metabolites of interest. Statistical analysis and mathematical modelling will use the laboratory results, along with the additional data collected from the farmers and residents, to determine systemic exposure levels amongst residents. Surveys will be carried out in selected areas of the United Kingdom over two years (2011 and 2012), covering two spraying seasons and the time between the spraying seasons. DISCUSSION: The described study protocol was implemented for the sample and data collection procedures carried out in 2011. Based on experience to date, no major changes to the protocol are anticipated for the 2012 spray season although the pesticides and regional areas for inclusion in 2012 are still to be confirmed. PMID- 22074398 TI - The Matthew effect in environmental science publication: a bibliometric analysis of chemical substances in journal articles. AB - BACKGROUND: While environmental research addresses scientific questions of possible societal relevance, it is unclear to what degree research focuses on environmental chemicals in need of documentation for risk assessment purposes. METHODS: In a bibliometric analysis, we used SciFinder to extract Chemical Abstract Service (CAS) numbers for chemicals addressed by publications in the 78 major environmental science journals during 2000-2009. The Web of Science was used to conduct title searches to determine long-term trends for prominent substances and substances considered in need of research attention. RESULTS: The 119,636 journal articles found had 760,056 CAS number links during 2000-2009. The top-20 environmental chemicals consisted of metals, (chlorinated) biphenyls, polyaromatic hydrocarbons, benzene, and ethanol and contributed 12% toward the total number of links- Each of the top-20 substances was covered by 2,000-10,000 articles during the decade. The numbers for the 10-year period were similar to the total numbers of pre-2000 articles on the same chemicals. However, substances considered a high priority from a regulatory viewpoint, due to lack of documentation, showed very low publication rates. The persistence in the scientific literature of the top-20 chemicals was only weakly related to their publication in journals with a high impact factor, but some substances achieved high citation rates. CONCLUSIONS: The persistence of some environmental chemicals in the scientific literature may be due to a 'Matthew' principle of maintaining prominence for the very reason of having been well researched. Such bias detracts from the societal needs for documentation on less well known environmental hazards, and it may also impact negatively on the potentials for innovation and discovery in research. PMID- 22074399 TI - Construction and humanization of a functional bispecific EGFR * CD16 diabody using a refolding system. AB - We previously reported the construction and activity of a humanized, bispecific diabody (hEx3) that recruited T cells towards an epidermal growth factor receptor (EGFR) positive tumor. Herein, we describe the construction of a second functional, fully humanized, anti-EGFR bispecific diabody that recruits another subset of lymphocyte effectors, the natural killer cells, to EGFR-expressing tumor cells. After we confirmed that an anti-EGFR * anti-CD16 bispecific diabody (Ex16) consisting of a previously humanized anti-EGFR variable fragment (Fv) and a mouse anti-CD16 Fv had growth inhibitory activity, we designed a humanized anti CD16 Fv to construct the fully humanized Ex16 (hEx16). However, the humanized form had lower activity for inhibition of cancer growth. To restore its growth inhibitory activity, we introduced mutations into the Vernier zone, which is located near the complementarity-determining regions and is involved in their binding activity. We efficiently prepared 15 different hEx16 mutants by expressing each chimeric single-chain component for hEx16 separately. We then used our in vitro refolding system to select the most functional mutant, which had a growth inhibitory effect comparable with that of the commercially available chimeric anti-EGFR antibody, cetuximab. Our refolding system could aid in the efficient optimization of other proteins with heterodimeric structure. PMID- 22074400 TI - Relevance of fluoroquinolone use in hospitals in the Lorraine region of France before and after corrective measures: an investigation by the Antibiolor Network. AB - OBJECTIVES: This study of fluoroquinolone use was carried out before and after an educational intervention run by Antibiolor, a regional network to all hospitals in the Lorraine region of France. METHODS: The relevance of fluoroquinolone prescription according to regional guidelines was assessed using a standard card filled out by physicians and pharmacists at the voluntarily participating hospitals. A therapeutic index of adequacy was established for each card. The initial survey took place in January 2008, with feedback and proposals for corrective measures in January 2009. The second survey was organized in June 2009. The results of the 2 surveys were compared. RESULTS: Twenty-four hospitals completed a total of 1336 cards in the first survey (S1) and 944 cards in the second (S2). The appropriateness of indications for fluoroquinolone use improved by 57% between the 2 surveys. All the criteria analyzed (choice of drug, dosage, treatment duration) were significantly improved in S2 compared to S1, as was the adequacy index (70% improvement). CONCLUSIONS: In view of the consequences of fluoroquinolone use, many hospitals in Lorraine were keen to participate in this study, confirming its feasibility over a large area. In view of the study results, the book of guidelines was re-examined and republished at the conclusion of S2. Greater adherence to guidelines was noted in S2, demonstrating the benefit of assessing the situation thoroughly before proposing corrective measures and evaluating their impact. PMID- 22074402 TI - Antimicrobial peptides: key components of the innate immune system. AB - Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs. PMID- 22074401 TI - Gallium compound GaQ(3) -induced Ca(2+) signalling triggers p53-dependent and independent apoptosis in cancer cells. AB - BACKGROUND AND PURPOSE A novel anti-neoplastic gallium complex GaQ(3) (KP46), earlier developed by us, is currently in phase I clinical trial. GaQ(3) induced S-phase arrest and apoptosis via caspase/PARP cleavage in a variety of cancers. However, the underlying mechanism of apoptosis is unknown. Here, we have explored the mechanism(s) of GaQ(3) -induced apoptosis in cancer cells, focusing on p53 and intracellular Ca(2+) signalling. EXPERIMENTAL APPROACH GaQ(3) -induced cytotoxicity and apoptosis were determined in cancer cell lines, with different p53 status (p53(+/+) , p53(-/-) and p53 mutant). Time course analysis of intracellular Ca(2+) calcium release, p53 promoter activation, p53 nuclear/cytoplasmic movements and reactive oxygen species (ROS) were conducted. Ca(2+) -dependent formation of the p53-p300 transcriptional complex was analysed by co-immunoprecipitation and chromatin immunoprecipitation. Ca(2+) signalling, p53, p300 and ROS were serially knocked down to study Ca(2+) -p53-ROS ineractions in GaQ(3) -induced apoptosis. KEY RESULTS GaQ(3) triggered intracellular Ca(2+) release stabilizing p53-p300 complex and recruited p53 to p53 promoter, leading to p53 mRNA and protein synthesis. p53 induced higher intracellular Ca(2+) release and ROS followed by activation of p53 downstream genes including those for the micro RNA mir34a. In p53(-/-) and p53 mutant cells, GaQ(3) -induced Ca(2+) -signalling generated ROS. ROS further increased membrane translocation of FAS and FAS-mediated extrinsic apoptosis. CONCLUSIONS AND IMPLICATIONS This study disclosed a novel mechanism of Ca(2+) -signalling-mediated p53 activation and ROS up-regulation. Understanding the mechanism of GaQ(3) -induced apoptosis will help establish this gallium-based organic compound as a potent anti-cancer drug. PMID- 22074404 TI - A point mutation at F1737 of the human Nav1.7 sodium channel decreases inhibition by local anesthetics. AB - Voltage-gated sodium channels (VGSC) contribute to the initiation and propagation of action potentials within the nervous system. These channels are important targets for inhibition by several classes of drugs, including antiarrhythmics and local anesthetics. Structural and pharmacological studies have localized the binding of these drugs to a common site near the channel's intracellular pore region. Point mutations within this region disrupt local anesthetic inhibition of cardiac, CNS, and skeletal muscle VGSC subtypes. This study was designed to test whether a similar structural requirement for drug binding exists on the peripheral neuronal VGSC subtype; Na(v)1.7. In support of this hypothesis, an alanine substitution for phenylalanine at position 1737 (F1737A) in the pore lining S6 segment of domain IV in human Na(v)1.7 reduced both use- and state- dependent inhibition of the local anesthetics, lidocaine and tetracaine, by 8-21 fold. We also saw a 2-3-fold reduction in tonic inhibition with the F1737A mutant. The voltage dependence of both activation and inactivation were unaffected by the F1737A mutation, however, fast inactivation kinetics were impaired, such that a significant portion of inward current remained at the end of a 20-ms depolarization. These data suggest that F1737 forms a part of the high affinity binding of local anesthetics as well as mediating inactivation processes of neuronal Na(v)1.7 channels. PMID- 22074405 TI - Highly selective colorimetric detection of hydrochloric acid using unlabeled gold nanoparticles and an oxidizing agent. AB - We report a colorimetric system for the detection of HCl in aqueous environments using unlabeled gold nanoparticle (AuNP) probes. This nonaggregation-based detection system relies on the ability of chloro species to cause rapid leaching of AuNPs in an aqueous dispersion containing a strong oxidizing agent, such as HNO(3) or H(2)O(2). The leaching process leads to remarkable damping of the surface plasmon resonance peak of the AuNP dispersion. This method works only with AuNPs of a particular size (~30 nm diameter). It is highly selective for HCl over several common mineral acids, salts, and anions. This simple and cost effective sensing system provides rapid and simple detection of HCl at concentrations as low as 500 ppm (far below the hazard limit) in natural water systems. PMID- 22074403 TI - Factors associated with the occurrence of MRSA CC398 in herds of fattening pigs in Germany. AB - BACKGROUND: The purpose of this study was to investigate the prevalence of MRSA in herds of fattening pigs in different regions of Germany, and to determine factors associated with the occurrence of this pathogen. For this purpose pooled dust samples were collected, and a questionnaire covered information regarding herd characteristics and management practices. Samples were pre-enriched in high salt medium followed by selective enrichment containing cefoxitin/aztreonam, and culturing. Presumptive colonies were confirmed by multiplex-PCR targeting nuc-, mecA- and 16S rRNA-genes. Isolates were spa- and SCCmec-, and in selected cases, multilocus sequence-typed. Susceptibilities to 13 antimicrobials were determined by broth microdilution. Statistical analysis was carried out using backward stepwise logistic regression to calculate odds ratios with the MRSA test result as the outcome and herd characteristics as categorical covariates. RESULTS: Overall, 152 of 290 (52%) fattening pig farms tested positive for MRSA. The prevalence in the east, north- and south-west of Germany ranged from 39 to 59%.t011 (66%) and t034 (23%) were the most commonly identified spa-types, and 85% of isolates carried SCCmec Type V. Identified spa-types were all associated with clonal complex CC398. Susceptibility testing revealed that all isolates were resistant to tetracycline. High resistance rates were also found for sulfamethoxazole/trimethoprim (40%), and quinupristin/dalfopristin (32%). In addition, 83% of strains displayed multidrug resistant (> 3 substance classes) phenotypes.Logistic regression revealed herd size (large farms OR: 5.4; CI: 2.7 11.2; p < 0.05), and production type (wean-to-finish OR: 4.0; CI: 1.6-10.4; p < 0.05) as risk factors associated with a positive MRSA finding in fattening pig operations. CONCLUSIONS: MRSA CC398 is widely distributed among herds of fattening pigs in Germany. Farm management plays a crucial role in the dissemination of MRSA with herd size, and production type representing potential major indicators. PMID- 22074406 TI - Primary cutaneous aspergillosis in a patient with systemic lupus erythematosus. PMID- 22074407 TI - Inflammatory diseases of the parathyroid gland. AB - AIMS: Inflammatory disorders of the parathyroid gland are very rare as compared with those of other endocrine organs. The aim of this study was to provide the first systematic review of this condition. METHODS AND RESULTS: A 42-year-old patient underwent surgery for recurrent secondary hyperparathyroidism. Histology showed hyperplastic parathyroiditis defined by a mixed inflammatory infiltrate with active germinal centres. Molecular markers revealed significant upregulation of CD68 in an ischaemic background (hypoxia-inducible factor 1 upregulation) with mitochondrial reaction (malate dehydrogenase 2 upregulation) and hyperparathyroidism (carbonic anhydrase 4 upregulation). Our case demonstrates true intraparathyroid inflammation with terminal B-cell differentiation. We searched PubMed, ISI Thompson and Google Scholar up to January 2011, using the terms 'parathyroiditis', 'inflammation of parathyroid gland', 'lymphocytic infiltrate', 'tuberculosis of the parathyroid', 'sarcoidosis', and 'graulomatous inflammation'. Three autopsy series, 27 articles and 96 case reports with inflammatory parathyroid disorders were identified. Autopsy series showed lymphocytic infiltrates in up to 16% of all cases. The entire material reported lymphocytic infiltrates (n=69), parathyroiditis with germinal centres (n=15), sarcoidosis (n=6), tuberculosis (n=4), and other granulomatous diseases (n=2). CONCLUSIONS: Distinct inflammatory and granulomatous processes in the parathyroid gland are rare. Scanty lymphocytic infiltrates are common, and occur in generalized inflammatory conditions or venous congestion. We note the surprising absence of an association between histological proof of parathyroiditis and hypoparathyroidism. PMID- 22074409 TI - Vicious dogs part 2: criminal thinking, callousness, and personality styles of their owners. AB - Every year over 885,000 dog bites require serious medical attention. Based on human injury and insurance claims, six dog breeds were designated as "vicious" (Akitas, Chows, Dobermans, Pit Bulls, Rottweilers, and Wolf-mixes). This study was conducted to expand on previous research examining antisocial tendencies and personality styles of people choosing to own vicious breeds. Seven hundred and fifty-four college students completed a questionnaire assessing type of dog owned, criminal thinking, callousness, personality, alcohol usage, and deviant lifestyle behaviors. Vicious dog owners reported significantly higher criminal thinking, entitlement, sentimentality, and superoptimism tendencies. Vicious dog owners were arrested, engaged in physical fights, and used marijuana significantly more than other dog owners. However, the homogeneous sample utilized could impact the generalizability of these findings. Choosing to own a vicious dog may be a "thin slice" indicator of more antisocial tendencies. PMID- 22074408 TI - Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level. AB - BACKGROUND: Calcitonin gene-related peptide (CGRP) has a key role in migraine pathophysiology and is associated with activation of the trigeminovascular system. The trigeminal ganglion, storing CGRP and its receptor components, projects peripheral to the intracranial vasculature and central to regions in the brainstem with Adelta- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal trigeminal nucleus (STN) and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) - in human and rat STN and at the C1-level, using a set of newly well characterized antibodies. In addition, double-stainings with CGRP and myelin basic protein (MBP, myelin), synaptophysin (synaptic vesicles) or IB4 (C-fibers in general) were performed. RESULTS: In the STN, the highest density of CGRP immunoreactive fibers were found in a network around fiber bundles in the superficial laminae. CLR and RAMP1 expression were predominately found in fibers in the spinal trigeminal tract region, with some fibers spanning into the superficial laminae. Co-localization between CGRP and its receptor components was not noted. In C1, CGRP was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal microscopy. CONCLUSIONS: This study demonstrates the detailed expression of CGRP and its receptor components within STN in the brainstem and in the spinal cord at C1-level, and shows the possibility of CGRP acting postjunctionally in these areas putatively involved in primary headaches. PMID- 22074410 TI - Imatinib mesylate for the treatment of pulmonary arterial hypertension. AB - INTRODUCTION: Despite recent advances, pulmonary arterial hypertension (PAH) remains a devastating disease which harbors a poor prognosis. Novel therapeutic approaches directly targeting pulmonary vascular remodeling are warranted. AREAS COVERED: This review delineates the current limitations in the management of PAH and focuses on a novel, anti-proliferative therapeutic concept. It will help readers understand the mechanisms of receptor tyrosine kinase signaling, with a special focus on platelet-derived growth factor (PDGF) receptors and their role in the pathobiology of PAH. Furthermore, it provides a comprehensive summary regarding the rationale, efficacy and safety of the tyrosine kinase inhibitor imatinib mesylate , which potently inhibits the PDGF receptor, as an additional treatment option in PAH. EXPERT OPINION: PDGF is a potent mitogen for pulmonary vascular smooth muscle cells and represents an important mediator of pulmonary vascular remodeling. Imatinib mesylate, a compound that inhibits the Bcr-Abl kinase and was developed for the treatment of chronic myeloid leukemia, also targets PDGF receptors. Both experimental and clinical data indicate that it reverses the vascular remodeling process even when it is fully established. Results from Phase II and III clinical trials suggest potent and prolonged efficacy in patients with severe PAH (i.e., pulmonary vascular resistance > 800 dynes*s*cm(-5)). Future studies should evaluate the long-term clinical efficacy and safety of imatinib, including patients with less impaired hemodynamics. Based on the current knowledge, this compound is likely to become an additional treatment option for patients with PAH and has the potential to at least partially correct the pathology of the disease. PMID- 22074411 TI - Rates of ionic reactions with charged nanoparticles in aqueous media. AB - A theory is developed to evaluate the electrostatic correction for the rate of reaction between a small ion and a charged ligand nanoparticle. The particle is assumed to generally consist of an impermeable core and a shell permeable to water and ions. A derivation is proposed for the ion diffusion flux that includes the impact of the equilibrium electrostatic field distribution within and around the shell of the particle. The contribution of the extra- and intraparticulate field is rationalized in terms of a conductive diffusion factor, f(el), that includes the details of the particle geometry (core size and shell thickness), the volume charge density in the shell, and the parameters defining the electrostatic state of the particle core surface. The numerical evaluation of f(el), based on the nonlinear Poisson-Boltzmann equation, is successfully complemented with semianalytical expressions valid under the Debye-Huckel condition in the limits of strong and weak electrostatic screening. The latter limit correctly includes the original result obtained by Debye in his 1942 seminal paper about the effect of electrostatics on the rate of collision between two ions. The significant acceleration and/or retardation possibly experienced by a metal ion diffusing across a soft reactive particle/solution interphase is highlighted by exploring the dependence of f(el) on electrolyte concentration, particle size, particle charge, and particle type (i.e., hard, core/shell, and entirely porous particles). PMID- 22074412 TI - Spinal cord stimulation with hybrid lead relieves pain in low back and legs. AB - OBJECTIVE: The failed back surgery syndrome (FBSS) is the most common chronic pain syndrome. Whereas it is relatively easy to achieve pain relief in the lower limbs of FBSS patients with spinal cord stimulation (SCS), it is difficult to manage low back pain with SCS. The performance of a paddle-shaped SCS lead that can be inserted surgically as well as percutaneously (a hybrid lead) was evaluated in a prospective study on the relief of low back pain and leg pain in patients with FBSS. MATERIALS AND METHODS: Patients with FBSS being eligible for SCS were enrolled in the study, and a hybrid lead was placed surgically. Outcome measures included pain scores for low back and leg pain assessed by visual analog scale (VAS), pain medication, and patient satisfaction. These scores were assessed before and at regular intervals after implantation. RESULTS: It was shown that a single hybrid lead, generally positioned over the physiological midline of the spinal cord, is capable of alleviating both low back and leg pain in patients with FBSS. Forty-five subjects were eligible for SCS and received trial stimulation. Forty-two of them had a successful trial period and were converted to a permanent system. Their average VAS score at baseline was 8.0 for lower limb pain and 7.5 for low back pain. After six months of SCS, these average VAS scores were reduced to 3.2 and 3.5, respectively, and also pain medication was reduced significantly. CONCLUSION: SCS with a hybrid lead in subjects with FBSS is safe, and causes significant pain relief in both the low back and the lower limbs. PMID- 22074414 TI - Feeling out of control: a qualitative analysis of the impact of bipolar disorder. AB - Bipolar disorder is a chronic and recurrent disorder with fluctuating symptoms. Few patients with bipolar disorder experience a simple trajectory of clear-cut episodes, with recovery typically occurring slowly over time. The chronic and disabling course of the disorder has a marked impact on the person's functioning and relationships with others. The objectives of this study were to investigate the impact of bipolar disorder on the lives of people diagnosed with this disorder. The method used was a general inductive qualitative approach. Twenty one participants were interviewed between 2008 and 2009 about how they had experienced the impact of bipolar disorder. The interviews were audio-taped and transcribed. The core theme that emerged was the participants were feeling out of control. Their own reactions and the reactions of others to the symptoms of bipolar disorder contributed to this core theme. The core theme was constituted by feeling overwhelmed, a loss of autonomy and felling flawed. Mental health nurses can help facilitate a sense of personal control for people with bipolar disorder by exploring what the symptoms mean for that person and implementing strategies to manage the symptoms, address social stigma and facilitate active involvement in treatment. PMID- 22074413 TI - The distribution of lung cancer across sectors of society in the United Kingdom: a study using national primary care data. AB - BACKGROUND: There is pressing need to diagnose lung cancer earlier in the United Kingdom (UK) and it is likely that research using computerised general practice records will help this process. Linkage of these records to area-level geo demographic classifications may also facilitate case ascertainment for public health programmes, however, there have as yet been no extensive studies of data validity for such purposes. METHODS: To first address the need for validation, we assessed the completeness and representativeness of lung cancer data from The Health Improvement Network (THIN) national primary care database by comparing incidence and survival between 2000 and 2009 with the UK National Cancer Registry and the National Lung Cancer Audit Database. Secondly, we explored the potential of a geo-demographic social marketing tool to facilitate disease ascertainment by using Experian's Mosaic Public Sector TM classification, to identify detailed profiles of the sectors of society where lung cancer incidence was highest. RESULTS: Overall incidence of lung cancer (41.4/100, 000 person-years, 95% confidence interval 40.6-42.1) and median survival (232 days) were similar to other national data; The incidence rate in THIN from 2003-2006 was found to be just over 93% of the national cancer registry rate. Incidence increased considerably with area-level deprivation measured by the Townsend Index and was highest in the North-West of England (65.1/100, 000 person-years). Wider variations in incidence were however identified using Mosaic classifications with the highest incidence in Mosaic Public Sector TMtypes 'Cared-for pensioners, ' 'Old people in flats' and 'Dignified dependency' (191.7, 174.2 and 117.1 per 100, 000 person-years respectively). CONCLUSIONS: Routine electronic data in THIN are a valid source of lung cancer information. Mosaic TM identified greater incidence differentials than standard area-level measures and as such could be used as a tool for public health programmes to ascertain future cases more effectively. PMID- 22074415 TI - Suppression of realgar cage degradation during complexation: formation of hybrid coordination polymers with As4S4, PAs3S3, and Cu(I) halide building blocks. AB - Realgar, As(4)S(4), reacts with Cr(CO)(5)THF under cage degradation to give As(4)S(3).Cr(CO)(5) (1). The reverse structural change is found if solutions of 1 in CH(2)Cl(2) react with equimolar amounts of PAs(3)S(3).W(CO)(5) and CuX (X = Cl, Br, I) in CH(3)CN under biphasic diffusion conditions. The resulting coordination polymers 2-4 contain a reconstituted realgar molecule along with the PAs(3)S(3) cage. The crystal structures of (CuX)(As(4)S(4))(PAs(3)S(3)) (X = Cl: 2; Br: 3) are characterized by one-dimensional (1D) (CuX)(As(4)S(4)) strands, which are formed by alternating As(4)S(4) cages and CuX dumbbells. Terminal PAs(3)S(3) molecules are coordinated to copper by apical phosphorus and bridging realgar through sulfur. The As(3) triangles of the resulting (CuX)(As(4)S(4))(PAs(3)S(3)) strands interact with halides of neighbored strands to give a folded three-dimensional (3D) network. The structure of (CuI)(3)(As(4)S(4))(PAs(3)S(3)) (4) contains 1D (Cu(3)I(3))(n) strands as backbones, which are bridged by sulfur atoms of two eta(1:2)-As(4)S(4) molecules while PAs(3)S(3) confines the resulting sheet. The As(3) triangles at the surface of the layers interact with iodide of the next layer to form a layered 3D network. PMID- 22074416 TI - Differences in adjustment by child developmental stage among caregivers of children with disorders of sex development. AB - BACKGROUND: The current study sought to compare levels of overprotection and parenting stress reported by caregivers of children with disorders of sex development at four different developmental stages. METHODS: Caregivers (N = 59) of children with disorders of sex development were recruited from specialty clinics and were asked to complete the Parent Protection Scale and Parenting Stress Index/Short Form as measures of overprotective behaviors and parenting stress, respectively. RESULTS: Analyses of covariance (ANCOVAs) were conducted to examine differences between caregiver report of overprotection and parenting stress. Results revealed that caregivers of infants and toddlers exhibited more overprotective behaviors than caregivers of children in the other age groups. Further, caregivers of adolescents experienced significantly more parenting stress than caregivers of school-age children, and this effect was driven by personal distress and problematic parent-child interactions, rather than having a difficult child. CONCLUSIONS: These results suggest that caregivers of children with disorders of sex development may have different psychosocial needs based upon their child's developmental stage and based upon the disorder-related challenges that are most salient at that developmental stage. PMID- 22074417 TI - Critical effects on attractive solutes in binary liquid mixtures close to their consolute point: a new experimental strategy. AB - The effect of near-criticality upon the properties of dilute solutions of attractive solutes has been previously studied only using pure solvents close to the vapor-liquid critical point. The experimental difficulties that plague this thermodynamic region have somewhat obscured the interpretations of the results. Consequently, the coupling of long-range critical fluctuations with short-range intermolecular interactions is still a matter of debate. We developed a new strategy consisting of studying the changes in the solvation shell of probe molecules dissolved in a binary solvent mixture close to its lower consolute critical point. The study is based on UV-vis absorption and fluorescent emission measurements of the solvatochromic and thermochromic effects of two dyes, Reichardt's Dye and Nile Red, dissolved in mixtures of lutidine-water. The results show unambiguously the existence of a subtle change in the composition of the near-critical solvent surrounding the probe molecules with respect to the bulk composition, thus we conclude that the coupling of long-range fluctuations with short-range interactions is now firmly established. PMID- 22074418 TI - One-step construction of tetrahydro-5H-indolo[3,2-c]quinolines from benzyl azides and indoles via a cascade reaction sequence. AB - A novel one-step assembly of tetrahydro-5H-indolo[3,2-c]quinolines from benzyl azides and indoles via a formal [4 + 2] cycloaddition is described. A cascade reaction sequence, which involves benzyl azide-to-iminium rearrangement followed by two sequential Pictet-Spengler reactions, generates the tetracycles in moderate to excellent yields. The current method is applicable to a broad substrate scope and holds significant potential in constructing polycyclic indolines with tertiary and/or quaternary carbon centers. PMID- 22074420 TI - Prodrugs: pharmaceutical design and current perspectives. PMID- 22074421 TI - L-Dopa prodrugs: an overview of trends for improving Parkinson's disease treatment. AB - L-Dopa is the mainstay of Parkinson's disease therapy; this drug is usually administered orally, but it is extensively metabolized in the gastrointestinal tract, so that relatively little arrives in the bloodstream as intact L-Dopa. The peripheral conversion of L-Dopa by amino acid decarboxylase to dopamine is responsible for the typical gastrointestinal and cardiovascular side effects. To minimize the conversion to dopamine outside the central nervous system, L-Dopa is usually given in combination with peripheral inhibitors of amino acid decarboxylase. In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for the poor bioavailability are the drug's physical chemical properties: low water and lipid solubility, resulting in unfavorable partition, and the high susceptibility to chemical and enzymatic degradation. Starting from these considerations the prodrug approach has been applied to L Dopa in order to overcome its metabolism problems and to improve its bioavailability. The goal of this paper is to provide the reader with a critical overview on L-Dopa prodrugs here classified according to the nature of the main chemical modification on L-Dopa backbone that led to the formation of the desired derivative. PMID- 22074419 TI - Associations of iron metabolism genes with blood manganese levels: a population based study with validation data from animal models. AB - BACKGROUND: Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism. METHODS: Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [delta-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data. RESULTS: Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) MUg/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (beta = -0.12 [95% CI = -0.23 to -0.01]). TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe(-/-) mice displayed a significant reduction in blood manganese compared with Hfe(+/+) mice, replicating the altered manganese metabolism found in our human research. CONCLUSIONS: Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements. PMID- 22074422 TI - Salicylanilide ester prodrugs as potential antimicrobial agents--a review. AB - Salicylanilides have been a subject of interest in medicinal chemistry as a group with a wide range of biological activities. The antibacterial (including antimycobacterial) and antifungal activities have come to be viewed as very significant. The synthesis of new prodrugs to counter a number of problematic properties of salicylanilides is a current trend. This article brings together the known basic facts about these prodrugs, particularly about the different mechanisms of the antimicrobial action of salicylanilides, including salicylanilide toxicity and undesired effects. The largest part of this group consists of antimicrobial salicylanilide esters with different organic acids, e.g. acetates, carbamates, esters with N-protected amino acids, and mutual antibacterial compounds with known antibacterial agents (beta-lactames and linezolid), with the activity and structure-activity relationships of these compounds being of particular interest. This review summarizes the activity of salicylanilides as potential virulence inhibitors attributable to a blockade of the type III secretion pathway. Many salicylanilide ester derivatives have been demonstrated an effective and promising treatment against pathogenic fungi and bacteria (especially against Gram-positive, tuberculous and atypical mycobacterial strains), including strains such as methicillin-resistant Staphylococcus aureus and isoniazid-resistant mycobacteria which are resistant to one or more clinically used drugs. PMID- 22074423 TI - Antimycobacterial evaluation of pyrazinoic acid reversible derivatives. AB - Design, results of in vitro antimycobacterial evaluation, and study of structure activity relationships of various pyrazinecarboxylic acid reversible derivatives are presented. This review deals with some pyrazinamide analogues/prodrugs derived from Nphenylpyrazine- 2-carboxamides (1), arylaminopyrazine-2,5 dicarbonitriles (2), aryl/alkylsulphanylpyrazines (3,4), and aroylpyrazines (5) effecting >50% inhibition in the primary antimycobacterial screen. The promising pyrazine candidates for further antimycobacterial evaluation were discovered. Results give good view onto structure-activity relationships of these analogues and promise even better activity of new compounds prepared after some structure optimization experiments. PMID- 22074424 TI - A prodrug approach to improve the physico-chemical properties and decrease the genotoxicity of nitro compounds. AB - In therapeutics research, the nitro compounds are part of an important group of drugs with multiple pharmacological activities. However, in drug design, the inclusion of a nitro group in a molecule changes the physico-chemical and electronic properties and is associated with increased mutagenicity and carcinogenicity. In addition, several studies have related the relationship between the antimicrobial and/or anti-protozoal activity and the mutagenic effect to reduction of the nitro group. This work reviews the toxicity of nitro compounds and shows how the use of prodrugs can increase the biological activity and decrease the genotoxicity of nitro compounds, without any modification in nitro reduction behavior, but rather by physico-chemical improvement. Examples are given of metronidazole and nitrofurazone prodrugs. PMID- 22074425 TI - Prodrugs for targeted tumor therapies: recent developments in ADEPT, GDEPT and PMT. AB - The treatment of cancer with common anti-proliferative agents generally suffers from an insufficient differentiation between normal and malignant cells which results in extensive side effects. To enhance the efficacy and reduce the normal tissue toxicity of anticancer drugs, numerous selective tumor therapies have emerged including the highly promising approaches ADEPT (Antibody-Directed Enzyme Prodrug Therapy), GDEPT (Gene-Directed Enzyme Prodrug Therapy) and PMT (Prodrug Monotherapy). These allow a selective release of cytotoxic agents from non-toxic prodrugs at the tumor site either by targeted antibody-enzyme conjugates, enzyme encoding genes or by exploiting physiological and metabolic aberrations in cancerous tissue. Herein, recent developments in the design and biological evaluation of prodrugs for use in ADEPT, GDEPT and PMT are reviewed. As a highlight, a series of novel glycosidic prodrugs based on the natural antibiotics CC-1065 and the duocarmycins will be discussed which show a therapeutic window of up to one million. Notably, the corresponding drugs have tremendously high cytotoxicities with IC(50) values of down to 110 fM. PMID- 22074426 TI - Prodrugs in photodynamic anticancer therapy. AB - Photodynamic therapy (PDT), the concept of cancer treatment through the selective uptake of a light-sensitive agent followed by exposure to a specific wavelength, is limited by the transport of a photosensitizer (PS) to the tumor tissue. Porphyrin, an important PS class, can be used in PDT in the form of its prodrug molecule 5-aminolevulinic acid (5-ALA). Unfortunately, its poor pharmacokinetic properties make this compound difficult to administer. Two different methods for eliminating this problem can be distinguished. The first approach is to play with its formulation in order to improve the drug's applicability. The second approach, which is to find possible 5- ALA prodrugs, is an example of the double prodrug method, a strategy often used in modern drug design. In this approach, the biological mechanisms in a long biosynthetic pathway involving several steps must be completed before the active drug appears. Recently, an idea of enhancing PDT sensitization using the so-called iron chelators seemed to increase the accumulation of protoporphyrin in cells. At the same time, iron chelators can destroy tumor cells by producing active oxygen after the formation of an active drug by chelating iron in the cancer cells. Thus, in the latter case, the therapy resembles a prodrug strategy. The mechanism can be explained by the Fenton reaction. Vitamin C is another example of a potential anticancer agent of this type. PMID- 22074427 TI - Prodrugs and endogenous transporters: are they suitable tools for drug targeting into the central nervous system? AB - Hydrophilic drugs, or neuroactive agents characterized by high molecular weight, do not have the physico-chemical properties required for passive diffusion across the blood brain barrier (BBB). The prodrug approach by lipidization of hydrophilic drugs generally allows to sensibly increase their permeability across BBB, even if this phenomenon is often not associated to an effective entry into the brain of the lipidized drugs. It has been understood that active efflux transporters (AET) can have a very important role in extruding from the brain not only prodrugs obtained by lipidization processes, but also lipophilic drugs. On the other hand, it has been also demonstrated that carrier mediated transporters (CMT), able to transfer essential nutrients and hormones from the bloodstream to the CNS, can be employed for the brain targeting of appropriated designed prodrugs. This approach consists on the chemical modification of a drug into a "pseudonutrient" or, differently, on drug conjugation to essential nutrients transported by CMT systems. This review focuses the molecular aspects that regulate the activity of the CMT and AET systems for the transport of their substrates, taking into account the in vitro and in vivo studies related to these transporters. The studies are described and summarized in the aim to evaluate the molecular keys for the design of prodrugs efficacious in the brain targeting. Among these, the molecular Trojan horses systems are briefly illustrated as carriers for the transport in the brain of large molecular weight neuroactive agents. PMID- 22074428 TI - Recent advances in the design and synthesis of prednisolone and methylprednisolone conjugates. AB - Glucocorticoid drugs are commonly used in the treatment of many acute and chronic inflammatory diseases. However, application of these steroids is limited because of their physico-chemical properties, such as very low water solubility. Glucocorticoids also exhibit serious adverse side effects. Therefore, new drug delivery systems are being developed, with the aim of improving the physicochemical properties of glucocorticoids while avoiding undesirable side effects associated with systemic administration. Here we discuss the design and synthesis of conjugates of prednisolone (PD), methylprednisolone (MPD) and similar glucocorticoids. In this review, possibilities for targeting inflammatory sites, and reducing dosages and administration frequency through increasing drug circulation time are discussed. This review summarises synthetic approaches for the preparation of covalent conjugates, which are divided into two groups: low molecular weight conjugates and polymeric conjugates. These two groups are further divided into subgroups based on the chemical structure of the conjugates. Published results from in vitro and in vivo testing of prepared conjugates are also discussed. PMID- 22074429 TI - Chitosan derivatives with antimicrobial, antitumour and antioxidant activities--a review. AB - Chitosan is a linear polysaccharide with a good biodegradability, biocompatibility, and no toxicity, which provide it with huge potential for future development. The chitosan molecule appears to be a suitable polymeric complex for many biomedical applications. This review gathers current findings on the antibacterial, antifungal, antitumour and antioxidant activities of chitosan derivatives and concurs with our previous review presenting data collected up to 2008. Antibacterial activity is based on molecular weight, the degree of deacetylation, the type of substitutents, which can be cationic or easily form cations, and the type of bacterium. In general, high molecular weight chitosan cannot pass through cell membranes and forms a film that protects cells against nutrient transport through the microbial cell membrane. Low molecular weight chitosan derivatives are water soluble and can better incorporate the active molecule into the cell. Gram-negative bacteria, often represented by Escherichia coli, have an anionic bacterial surface on which cationic chitosan derivatives interact electrostatically. Thus, many chitosan conjugates have cationic components such as ammonium, pyridinium or piperazinium substituents introduced into their molecules to increase their positive charge. Gram-positive bacteria like Staphylococcus aureus are inhibited by the binding of lower molecular weight chitosan derivatives to DNA or RNA. Chitosan nanoparticles exhibit an increase in loading capacity and efficacy. Antitumour active compounds such as doxorubicin, paclitaxel, docetaxel and norcantharidin are used as drug carriers. It is evident that chitosan, with its low molecular weight, is a useful carrier for molecular drugs requiring targeted delivery. The antioxidant scavenging activity of chitosan has been established by the strong hydrogen-donating ability of chitosan. The low molecular weight and greater degree of quarternization have a positive influence on the antioxidant activity of chitosan. Phenolic and polyphenolic compounds with antioxidant effects are condensed with chitosan to form mutual prodrugs. PMID- 22074430 TI - There is more to predicting vascular disease than just established risk factors. PMID- 22074431 TI - (Pro)renin receptor as a new drug target. AB - Over the last few years, the implication of the (pro)renin receptor [(P)RR] in the pathogenesis of end-organ damage has been shown through many different studies. The (P)RR plays a dual role when stimulated by renin or prorenin as it enhances both cell surface production of angiotensin and stimulates angiotensin independent intracellular signaling cascades. Since Ichihara's group demonstrated activation of prorenin when it was bound to antibodies targeted against a specific region in the renin prosegment, they designed a complementary decapeptide to this region called the handle region to use as a potential (P)RR blocker (PRRB). The effects of systemic administration of the PRRB on the development and progression of different renal, cardiac and ocular pathologies have been observed and have thus proposed the blocker as a potential new treatment for these afflictions. Conversely, the specificity of the PRRB has been questioned as conflicting results have been reported in the literature. A recent study has described a new high affinity binding site for renin and prorenin to the (P)RR called the hinge region. Hence, although there is great promise in the (P)RR potential as a therapeutic target, still much research is required to better identify adequate blockers. PMID- 22074432 TI - Lipid lowering drugs and gallstones: a therapeutic option? AB - Cholelithiasis is a common disease worldwide. The majority of gallstones can occur when the bile is supersaturated with cholesterol. Dyslipidaemia, obesity, insulin resistance are associated with an increased risk for cholesterol gallstone formation as well as with vascular risk. Statins and ezetimibe are used to treat dyslipidaemia and appear to have some effect on bile composition and cholesterol gallstone formation. Statin (e.g. pravastatin, simvastatin, fluvastatin and lovastatin) monotherapy or combined with ursodeoxycholic acid (UDCA) have shown reductions in bile cholesterol saturation, preventing gallstone formation and even dissolving pre-existing stones. However, this effect was not consistently reported in all studies. Statin use has also been associated with a reduced risk for cholecystectomy in 2 large epidemiological studies. Ezetimibe was shown to have a beneficial action against cholelithiasis in animal studies but data in humans - although promising - are very limited. The effect of these drugs on gallstone disease warrants further investigation in large human trials. We also consider the links between cholelithiasis, vascular risk and the use of lipid lowering drugs. PMID- 22074433 TI - Liver enzymes: potential cardiovascular risk markers? AB - Several cross-sectional studies have reported a relationship between elevated serum activity of liver enzymes [e.g. alanine aminotransferase (ALT) and gamma glutamyltransferase (gammaGT)] and metabolic syndrome (MetS) and/or diabetes mellitus (DM). Raised serum activity of liver enzymes independently predicted the future development of MetS and DM as well as cardiovascular (CV) events and/or total/CV mortality in prospective studies. However, this association was not consistently demonstrated and it appears to be independent of alcohol intake. Even though these associations can be partly attributed to non-alcoholic fatty liver disease (NAFLD) and insulin resistance, there may be additional underlying mechanisms that contribute to the increased CV risk (e.g. inflammation and oxidative stress). The association of gammaGT with atherosclerotic plaque is of particular importance. PMID- 22074434 TI - Is bilirubin a marker of vascular disease and/or cancer and is it a potential therapeutic target? AB - Normal aerobic metabolism is associated with reactive oxygen species (ROS) that can damage cellular macromolecules. Analogous free radicals are formed by exposure to ionizing radiation and many dietary products are considered to contain free radical generators. During the past 15 years epidemiological studies and animal experiments have identified bilirubin as a molecule at the crossroads of the protection of the body against ROS. The studies have focused on bilirubin as a biomarker of arterial disease. This review assesses the current state of evidence and sets the data in context. There is no definitive evidence from prospective studies of a causal protective effect from bilirubin in arterial disease or that various genetic polymorphisms, (particularly the 7/7 UGT1A1 repeat polymorphism) impacts coronary artery disease. There is no definitive evidence that high bilirubin levels confer protection against cancer. There is some preliminary evidence that bilirubin may have a protective effect in lung disease and stroke, but the reports have yet to be confirmed. The role of various genotypes of UGT1A1 and HMOX1, if any, in cancer is unclear. PMID- 22074435 TI - Therapeutic modulation of lipoprotein-associated phospholipase A2 (Lp-PLA2). AB - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a calcium-independent phospholipase A2 that circulates in plasma in association with lipoprotein particles, whereas in atherosclerotic plaques it is co-localized with macrophages. Lp-PLA2 generates two proinflammatory mediators, lysophosphatidylcholine and oxidized nonesterified fatty acids, which play a role in the development of atherosclerotic lesions and formation of a necrotic core, leading to more vulnerable plaques. Epidemiologic studies demonstrate that increased circulating levels of Lp-PLA2 predict an increased risk of myocardial infarction, stroke and cardiovascular mortality. Furthermore, histologic examination of diseased human coronary arteries reveals intense presence of the enzyme in atherosclerotic plaques that are prone to rupture. These considerations suggest Lp-PLA2 as a promising therapeutic target in cardiovascular disease. Plasma levels of Lp-PLA2 are increased in various types of hyperlipidemias, while hypolipidemic drugs reduce plasma Lp-PLA2 activity and mass along with the improvement of plasma lipid profile. A selective inhibitor of Lp-PLA2 activity, darapladib, has been developed and studies in animal models and humans have shown that it effectively and safely reduces Lp-PLA2 activity in plasma and in atherosclerotic plaques. Furthermore, in animal models darapladib decreases plaque area and necrotic core area whereas in humans it prevents the expansion of necrotic core volume. Whether the results obtained from the use of darapladib in studies in vitro, as well as in preclinical and clinical studies would translate into benefits on cardiovascular event outcomes, awaits to be proved in 2 ongoing phase 3 trials. PMID- 22074436 TI - Heat shock protein-60 and risk for cardiovascular disease. AB - Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. There is growing evidence that molecular chaperones, many of which are heat shock proteins HSPs, are involved in CVD pathogenesis. In this review we focus on HSP60, the human mitochondrial chaperone that also displays extramitochondrial and extracellular functions. HSP60 is typically cytoprotective but a number of stress conditions determine its conversion to a potentially toxic molecule for cells and tissues. We present illustrative examples of specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicate a pathogenic role for HSP60 but also its potential as a biomarker with applications for diagnosis, assessing prognosis and response to treatment, as well as for preventing and treating CVD. PMID- 22074437 TI - Statin discontinuation in high-risk patients: a systematic review of the evidence. AB - Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. Since the late 1980s, statins have emerged as effective lipid-lowering therapies and are now widely used to protect against and slow the progression of CVD and cerebrovascular disease. However, there is a significant gap between disease improvement in clinical trials and daily practice possibly attributable to poor adherence with statin therapy. High discontinuation rates were reported in primary and secondary prevention. This systematic review aims to summarize the current literature regarding the association between statin therapy discontinuation and cardiovascular and cerebrovascular events and all cause mortality in high-risk patients. Available English literature was reviewed using Medline, Embase, Web of Sciences and the Cochrane Library; 39 studies were identified. In primary and secondary prevention, as well as perioperatively, non adherence or discontinuation of statin therapy was associated with detrimental effects on cardiovascular and cerebrovascular outcomes, including disease severity and mortality. Importantly, some studies reported that very low adherence and discontinuation was associated with worse outcomes than never using statins. In conclusion, non-adherence and discontinuation of statin therapy significantly increased the incidence of cardiovascular and cerebrovascular events as well as all-cause mortality in high-risk patients. Patients would therefore benefit from closer adherence assessment and education programs aimed at increasing awareness of the risk associated with discontinuation of statin therapy. PMID- 22074438 TI - Role of physician gender in the quality of care of cardiometabolic diseases. AB - Evidence suggests that patient gender is associated with the quality of care provided in the treatment of cardiometabolic diseases. The majority of findings suggest that female patients receive less intensified care than male patients. However, the question whether physician gender plays a role in the quality of care has been debated for some time. For example, it has been postulated that the practice styles of female physicians, such as spending more time with a patient, hearing and listening more effectively, and including more preventive measures, may result in more efficient clinical encounters that may positively affect clinical outcomes. This narrative review examines the existing evidence regarding the effects of physician gender on the quality of care provided, focusing mainly on patients with cardiometabolic diseases. PMID- 22074439 TI - Evaluation of the possible contribution of antioxidants administration in metabolic syndrome. AB - The metabolic syndrome (MetS) is common, and its associated risk burdens of diabetes and cardiovascular disease (CVD) are a major public health problem. The hypothesis that main constituent parameters of the MetS share common pathophysiologic mechanisms provides a conceptual framework for the future research. Exercise and weight loss can prevent insulin resistance and reduce the risk of diseases associated with the MetS. Interrupting intracellular and extracellular reactive oxygen species (ROS) overproduction could also contribute to normalizing the activation of metabolic pathways leading to the onset of diabetes, endothelial dysfunction, and cardiovascular (CV) complications. On the other hand, it is difficult to counteract the development of CV complications by using conventional antioxidants. Indeed, interest has focused on strategies that enhance the removal of ROS using either antioxidants or drugs that enhance endogenous antioxidant defense. Although these strategies have been effective in laboratory experiments, several clinical trials have shown that they do not reduce CV events, and in some cases antioxidants have actually worsened the outcome. More research is needed in this field. PMID- 22074441 TI - European veterinary dissertations. PMID- 22074440 TI - DNA binding activity of Helicobacter pylori DnaB helicase: the role of the N terminal domain in modulating DNA binding activities. AB - Replicative helicases are major motor proteins essential for chromosomal DNA replication in prokaryotes. Usually hexameric in solution, their DNA binding property must have different roles at stages ranging from the loading onto a branched structure at initiation from the origin to the highly processive translocation during elongation. Here, we have analysed the DNA binding activity of Helicobacter pylori (Hp) replicative helicase, DnaB. The results indicate that while the C-terminal region is important for its DNA binding activity, the N terminus appears to dampen the protein's affinity for DNA. The masking activity of the N-terminus does not require ATP or hexamerization of HpDnaB and can be overcome by deleting the N-terminus. It can also be neutralized by engaging the N terminus in an interaction with a partner like the C-terminus of DnaG primase. The inhibitory effect of the N-terminus on DNA binding activity is consistent with the 3D homology model of HpDnaB. Electron microscopy of the HpDnaB-ssDNA complex showed that HpDnaB preferentially bound at the ends of linear ssDNA and translocated along the DNA in the presence of ATP. These results provide an insight into the stimulatory and inhibitory effects of different regions of HpDnaB on DNA binding activities that may be central to the loading and translocation functions of DnaB helicases. PMID- 22074442 TI - A new species of Spauligodon (Nematoda: Oxyuroidea: Pharyngodonidae) in Gonatodes antillensis (Squamata: Sphaerodactylidae) from Bonaire, Lesser Antilles. AB - Spauligodon bonairensis n. sp. from the large intestines of the Antilles gecko, Gonatodes antillensis (Lacertidae), from Bonaire, Lesser Antilles, is described and illustrated. The new species is the 48th assigned to the genus and the 10th from the Neotropical region. Spauligodon bonairensis n. sp. is most similar to S. giganticus, S. hemidactylus, S. lamonthei, and S. oxkutzcabiensis in that only these 5 species possess lanceolate eggs. For males of these species, only S. lamothei possess a spicule, and only S. oxktzcabiensis has an aspinose tail. The egg of S. hemidactylus has 2 knobs; in S. giganticus, the more rounded end supports the single knob. In S. bonairensis n. sp., the more pointed end supports the single knob. PMID- 22074443 TI - Bioinorganic chemistry of titanium. PMID- 22074444 TI - Extraction of DNA from malaria-infected erythrocytes using isotachophoresis. AB - We demonstrate a technique for purification of nucleic acids from malaria parasites infecting human erythrocytes using isotachophoresis (ITP). We release nucleic acids from malaria-infected erythrocytes by lysing with heat and proteinase K for 10 min and immediately, thereafter, load sample onto a capillary device. We study the effect of temperature on lysis efficiency. We also implement pressure-driven counterflow during ITP extraction to extend focusing time and increase nucleic acid yield. We show that the purified genomic DNA samples are compatible with polymerase chain reaction (PCR) and demonstrate a clinically relevant limit of detection of 0.5 parasites per nanoliter using quantitative PCR. PMID- 22074445 TI - Determination of HIV status of infants born to HIV-infected mothers: a review of the diagnostic methods with special focus on the applicability of p24 antigen testing in developing countries. AB - In 2009, 2.5 million children under the age of 15 y were living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS); 370,000 were diagnosed with HIV and 260,000 died due to AIDS. More than 90% of the children infected with HIV live in sub-Saharan Africa. Most children infected with HIV contract the infection in utero, during delivery, or via breast milk. This review outlines the current diagnostic methods to determine the HIV status of infants born to HIV-infected mothers. The HIV DNA and RNA polymerase chain reaction (PCR) tests are highly accurate and are recommended as the first-choice diagnostic methods. However, they are expensive and require complex laboratory procedures. Consequently, a search for less costly and complicated methods has led to the testing of p24 antigen analyses as an alternative to the gold-standard PCR tests, with encouraging results. The p24 antigen Perkin Elmer assay currently most often used has a sensitivity of 98.8% and a specificity of 100% (infants 6 weeks of age). Larger-scale studies should be performed in resource-limited settings to confirm these findings. PMID- 22074446 TI - Successful and unsuccessful cannabis quitters: comparing group characteristics and quitting strategies. AB - BACKGROUND: In order to improve treatments for cannabis use disorder, a better understanding of factors associated with successful quitting is required. METHOD: This study examined differences between successful (n=87) and unsuccessful (n=78) cannabis quitters. Participants completed a questionnaire addressing demographic, mental health, and cannabis-related variables, as well as quitting strategies during their most recent quit attempt. RESULTS: Eighteen strategies derived from cognitive behavioral therapy were entered into a principal components analysis. The analysis yielded four components, representing (1) Stimulus Removal, (2) Motivation Enhancement, (3) (lack of) Distraction, and (4) (lack of) Coping. Between groups comparisons showed that unsuccessful quitters scored significantly higher on Motivation Enhancement and (lack of) Coping. This may indicate that unsuccessful quitters focus on the desire to quit, but do not sufficiently plan strategies for coping. Unsuccessful quitters also had significantly more symptoms of depression and stress; less education; lower exposure to formal treatment; higher day-to-day exposure to other cannabis users; and higher cannabis dependence scores. CONCLUSIONS: The findings suggest that coping, environmental modification, and co-morbid mental health problems may be important factors to emphasize in treatments for cannabis use disorder. PMID- 22074447 TI - Radiation-induced primitive neuroectodermal tumour - a rare cause and consequence. PMID- 22074448 TI - High resolution melting analysis for the detection of EMS induced mutations in wheat SBEIIa genes. AB - BACKGROUND: Manipulation of the amylose-amylopectin ratio in cereal starch has been identified as a major target for the production of starches with novel functional properties. In wheat, silencing of starch branching enzyme genes by a transgenic approach reportedly caused an increase of amylose content up to 70% of total starch, exhibiting novel and interesting nutritional characteristics. In this work, the functionality of starch branching enzyme IIa (SBEIIa) has been targeted in bread wheat by TILLING. An EMS-mutagenised wheat population has been screened using High Resolution Melting of PCR products to identify functional SNPs in the three homoeologous genes encoding the target enzyme in the hexaploid genome. RESULTS: This analysis resulted in the identification of 56, 14 and 53 new allelic variants respectively for SBEIIa-A, SBEIIa-B and SBEIIa-D. The effects of the mutations on protein structure and functionality were evaluated by a bioinformatic approach. Two putative null alleles containing non-sense or splice site mutations were identified for each of the three homoeologous SBEIIa genes; qRT-PCR analysis showed a significant decrease of their gene expression and resulted in increased amylose content. Pyramiding of different single null homoeologous allowed to isolate double null mutants showing an increase of amylose content up to 21% compared to the control. CONCLUSION: TILLING has successfully been used to generate novel alleles for SBEIIa genes known to control amylose content in wheat. Single and double null SBEIIa genotypes have been found to show a significant increase in amylose content. PMID- 22074449 TI - Day-case stapedotomy: is it a viable option? AB - CONCLUSIONS: Stapedotomy is, in our opinion, the technique of choice in stapes surgery. The precision of this technique allows clinicians to perform the surgical procedure in day surgery under local anesthesia. OBJECTIVES: There is a strong emphasis on increasing the number of elective day surgery cases, especially in the patients' best interest, as it decreases the likelihood of late cancellation and hospital-acquired morbidity. A prospective study was performed to determine whether stapes surgery for otosclerosis could be performed safely in an outpatient setting. METHODS: We present a series of stapes surgery cases for otosclerosis performed on a day-case basis. We performed a classic stapedotomy in 9 patients, a reverse classic step stapedotomy in 2 patients, a partial reverse classic step stapedotomy in 11 patients, and a hemi-stapedectomy in two patients. RESULTS: Three of 24 patients (12.5%) treated with classic stapedotomy, 1 patient with partial reverse classic step stapedotomy, and 1 patient with hemi stapedectomy were formally admitted to the hospital after surgery (length of stay, 23 h). The indications were vertigo (two patients) and asthenia (one patient). These patients were treated under general anesthesia. Two of these patients resided more than 250 km away from the hospital. PMID- 22074450 TI - Temporal changes in the prevalence of childhood asthma and allergies in urban and rural areas of Cyprus: results from two cross sectional studies. AB - BACKGROUND: The prevalence of childhood asthma and allergies in Cyprus was significantly higher in urban compared to rural areas back in the year 2000, against a background of an overall low prevalence (e.g. current wheeze 6.9%) by comparison to northern European countries. In this study we aimed to assess temporal changes in the prevalence of asthma and allergies in Cyprus after an 8 year interval and to examine whether any differential changes have occurred in urban and rural parts of the island. METHODS: During the academic years 1999-2000 and 2007-2008, the parents of 7-8 year old children residing in the same set of urban and rural areas completed the ISAAC core questionnaire. In addition to providing prevalence estimates of allergic diseases in 2000 and 2008, changes between the two periods were expressed as odds ratios estimated in multiple logistic regression models adjusting for survey participants' characteristics. RESULTS: The prevalence of current wheeze was higher in 2008 (8.7%, 95% confidence interval 7.5%-9.9%, n = 2216) than the previously recorded figure in 2000 (6.9%, 95% CI 6.2%-7.6%, OR = 1.25, 95% CI: 1.02-1.53, n = 4944). Significant increases were also seen in the prevalence of lifetime asthma (11.3% vs. 17.4%, OR = 1.59, CI: 1.36-1.86), eczema (6.8% vs. 13.5%, OR = 1.91, CI: 1.59 2.29) and allergic rhinoconjuctivitis (2.6% vs. 5.2%, OR = 1.82, CI: 1.39-2.41). The prevalence of current wheeze nearly doubled between 2000 and 2008 in rural areas (5.4% vs. 9.7%, OR 1.81, CI: 1.24-2.64) while no significant change was observed in urban areas (7.5% vs. 8.4%, OR 1.08, CI: 0.84-1.37); p value for effect modification = 0.04. Rises in asthma and rhinitis prevalence, but not eczema were also more pronounced in rural compared to urban areas. CONCLUSIONS: The prevalence of allergic diseases in Cyprus is still on the rise; recent increases appear more pronounced among children living in rural areas possibly indicating recent environmental and lifestyle changes in these communities. PMID- 22074451 TI - Exploring ancestral variation of the hyoid. AB - This study utilizes metric analysis to examine size and shape variation between hyoids of Africans and Europeans in the Robert J. Terry Anatomical Collection. A total of 200 fused and unfused hyoids were measured and three statistical methods were employed to explore variation between ancestries. First, independent sample t-tests showed that some significant size differences do occur between ancestries. Second, to examine shape variation, skeletal measurements were regressed on the geometric mean using least squares linear regression with the residuals used to evaluate size-corrected shape differences. Finally, discriminant function analysis was used to develop two functions for ancestry prediction with overall accuracies of 73% and 77%. Results of the analyses suggest hyoid size and shape differences do occur between ancestries, notably that European hyoids are broader than African hyoids, while the African hyoid is longer than Europeans. PMID- 22074452 TI - Solution NMR evidence for symmetry in functionally or crystallographically asymmetric homodimers. AB - A recurrent theme of many structural studies of homo-oligomeric protein systems is concerned with verification that the conformation observed in a crystal represents the functionally relevant structure. An asymmetric conformation adopted by two chemically identical subunits in homo-oligomers can represent an intrinsic property of a protein or be an artifact induced by crystal packing forces. Solution NMR studies can distinguish between these two possibilities. Using methyl-based NMR spectroscopy, we provide evidence for symmetry in the absence of ligands in several homodimeric proteins that are either asymmetric functionally and/or adopt different conformations of the two subunits in available X-ray structures. PMID- 22074453 TI - A study comparing plasmakinetic enucleation with bipolar plasmakinetic resection of the prostate for benign prostatic hyperplasia. AB - BACKGROUND AND PURPOSE: Plasmakinetic enucleation of the prostate (PKEP) has been reported to be a new method for the transurethral management of benign prostatic hyperplasia (BPH). Our objective was to compare the safety and efficiency of PKEP with that of bipolar plasmakinetic resection of the prostate (PKRP) in the management of BPH. PATIENTS AND METHODS: A total of 303 patients with lower urinary tract symptoms associated with BPH were included in our study. Of these, 143 patients underwent PKRP and 160 underwent PKEP. All patients were preoperatively assessed and evaluated at 3 months after surgery. International Prostate Symptom Score (IPSS), quality of life (QoL), postvoid residual urine (PVRU) volume, and maximum flow rate (Qmax) were obtained at the follow-up. The perioperative data and postoperative outcomes were compared. Immediate and late complications were recorded. RESULTS: There were no significant differences between the two surgical groups preoperatively. The mean prostate volumes in the PKRP and PKEP groups were 75.6 cc and 77.3 cc, respectively. Both groups were similar with respect to operative time, resected tissue weight, catheterization time, and the total length of hospital stay. The blood loss observed in the PKEP group was significantly less than that of conventional PKRP (P<0.0001). PKEP was significantly superior to PKRP in terms of the transient incontinence in the postoperative period (P=0.03). Both groups resulted in a significant improvement from baseline in terms of IPSS, QoL, Qmax, and PVRU volume values. No significant difference was found between them, however. CONCLUSIONS: PKEP is a safe and effective method for the transurethral management of BPH. Compared with PKRP, the main advantage of PKEP is the decreased risk of blood loss and transient incontinence. PMID- 22074454 TI - A tale of two mRNA degradation pathways mediated by RNase E. AB - RNase E is an essential endoribonuclease with a preference for RNA substrates with 5'-monophosphate ends. Primary transcripts, which have 5' triphosphate ends, are thus protected from RNase E. Their conversion to 5'-monophosphate transcripts by RppH is a prerequisite for RNase E-mediated processing and degradation. 5' monophosphate recognition involves binding to a subdomain in the catalytic core of RNase E known as the 5' sensor. There are, however, transcripts that can be attacked directly by RNase E in a 5'-end-independent pathway. Direct entry involves elements outside of the catalytic domain that are located in the carboxyl terminal half (CTH) of RNase E. Strains harbouring rne alleles that express variants of RNase E in which 5' sensing (rneR169Q) or direct entry (rneDeltaCTH) are inactivated, are viable. However, the rneR169Q/rneDeltaCTH and DeltarppH/rneDeltaCTH combinations are synthetic lethal suggesting that the essential function(s) of RNase E requires at least one of these pathways to be active. A striking result is the demonstration that mutations affecting Rho dependent transcription termination can overcome synthetic lethality by a pathway that requires RNase H. It is hypothesized that R-loop formation and RNase H cleavage substitute for RNase E-dependent RNA processing and mRNA degradation. PMID- 22074455 TI - Rechargeable internal neural stimulators--is there a problem with efficacy? AB - INTRODUCTION: With the advent of rechargeable internal neural stimulators (rINS) for deep brain stimulation, our aim was to survey patient satisfaction and clinical efficacy in an early cohort of patients receiving this new technology. METHODS: This is an observational study on nine patients with rINS. All patients had initially received non-rechargeable INS with established efficacy of their deep brain stimulation system for either dystonia or pain. Patient satisfaction and efficacy with their rINS were established by completion of a questionnaire, a quality of life assessment (SF-36), and calculation of the total electrical energy delivered (TEED) by the rINS. RESULTS: A reduction in efficacy of their rINS was noticed in 22% of patients. In 78% of patients, there was a problem with recharging their rINS because of poor contact. Two patients (22%) felt that recharging the rINS interfered with their lives and it was a daily reminder that they had a deep brain stimulator system in situ. Eight out of nine patients (89%), however, would recommend to other patients to have an rINS. CONCLUSION: Most patients were happy with their rechargeable internal neural stimulator. A reduction in efficacy was noticed in 22% of patients, which is similar to the proportion of patients noticing a reduction in efficacy when replacing with a non rechargeable system. Thus, all patients require close monitoring post-replacement of rINS, in case possible adjustment of parameters is required. PMID- 22074456 TI - Destruction of chloroanisoles by using a hydrogen peroxide activated method and its application to remove chloroanisoles from cork stoppers. AB - A chemical method for the efficient destruction of 2,4,6-trichloroanisole (TCA) and pentachloroanisole (PCA) in aqueous solutions by using hydrogen peroxide as an oxidant catalyzed by molybdate ions in alkaline conditions was developed. Under optimal conditions, more than 80.0% TCA and 75.8% PCA were degraded within the first 60 min of reaction. Chloroanisoles destruction was followed by a concomitant release of up to 2.9 chloride ions per TCA molecule and 4.6 chloride ions per PCA molecule, indicating an almost complete dehalogenation of chloroanisoles. This method was modified to be adapted to chloroanisoles removal from the surface of cork materials including natural cork stoppers (86.0% decrease in releasable TCA content), agglomerated corks (78.2%), and granulated cork (51.3%). This method has proved to be efficient and inexpensive with practical application in the cork industry to lower TCA levels in cork materials. PMID- 22074457 TI - Absolute intensities of NH-stretching transitions in dimethylamine and pyrrole. AB - Vibrational spectra of vapor-phase dimethylamine (DMA) and pyrrole have been recorded in the 1000 to 13000 cm(-1) region using long path conventional spectroscopy techniques. We have focused on the absolute intensities of the NH stretching fundamental and overtone transitions; Deltanu(NH) = 1-4 regions for DMA and the Deltanu(NH) = 1-3 regions for pyrrole. In the Deltanu(NH) = 1-3 regions for DMA, evidence of tunneling splitting associated with the NH-wagging mode is observed. For DMA, the fundamental NH-stretching transition intensity is weaker than the first NH-stretching overtone. Also, the fundamental NH-stretching transition in DMA is much weaker than the fundamental transition in pyrrole. We have used an anharmonic oscillator local mode model with ab initio calculated local mode parameters and dipole moment functions at the CCSD(T)/aug-cc-pVTZ level to calculate the NH-stretching intensities and explain this intensity anomaly in DMA. PMID- 22074458 TI - The lifeworld characteristics of mental health nurses engaging in talk-based therapies: a qualitative study from Scotland and England. AB - Twenty-four mental health nurses were interviewed to gain a greater understanding of their experiences of working within roles delivering talk-based therapies. The study participants, while echoing the broad direction and purpose of policy that supports mental health nurses expanding talk-based therapy roles, also offered insights into the challenges associated with embedding these roles into mental health settings. One area of findings analysed using Nvivo 8 software related to the characteristics of the environments in which these roles are, or will be enacted. Three key characteristics of these environments were: (1) low power and worth; (2) obstacles to success; and (3) uncertainty. Responses to the challenges found within this study are required from individual nurses, local organizations and strategic levels of nursing to ensure the successful implementation and uptake of talk-based therapy roles into the mental health nursing profession. PMID- 22074461 TI - Chiroptical spectra of a series of tetrakis((+)-3 heptafluorobutylyrylcamphorato)lanthanide(III) with an encapsulated alkali metal ion: circularly polarized luminescence and absolute chiral structures for the Eu(III) and Sm(III) complexes. AB - The luminescence and circularly polarized luminescence (CPL) spectra of M(I)[Eu((+)-hfbc)(4)] show a similar behavior to the exciton CD in the intraligand pi-pi* transitions when the alkali metal ions and solvents are manipulated. There is a difference in susceptibility in solvation toward the alkali metal ions but not toward the Eu(III) ion, as in the case of axially symmetric DOTA-type compounds. The remarkable CPL in the 4f-4f transitions provide much more information on the stereospecific formation of chiral Eu(III) complexes, since CPL spectroscopy is limited to luminescent species and reflects selectively toward helicity of the local structural environment around the lanthanide(III). While in comparison, exciton CD reveals the chiral structural information from the helical arrangement of the four bladed chelates. Of special importance, the observation of the highest CPL activities measured to date for lanthanide(III)-containing compounds (i.e., Eu and Sm) in solution supports the theory that the chirality of lanthanide(III) in the excited state corresponds to that in the ground state, which was derived from the exciton CD. PMID- 22074462 TI - Oxazole as an electron-deficient diene in the Diels-Alder reaction. AB - The Diels-Alder cycloaddition reaction of oxazole with ethylene is facilitated by addition of an alkyl group or Bronsted or Lewis acids to the oxazole nitrogen atom. The efficacy consists of stabilizing the transition state, lowering the activation barrier and the HOMO(dienophile)-LUMO(diene) gap, and increasing the reaction exothermicity. PMID- 22074460 TI - Pro-inflammatory gene expression and neurotoxic effects of activated microglia are attenuated by absence of CCAAT/enhancer binding protein beta. AB - BACKGROUND: Microglia and astrocytes respond to homeostatic disturbances with profound changes of gene expression. This response, known as glial activation or neuroinflammation, can be detrimental to the surrounding tissue. The transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) is an important regulator of gene expression in inflammation but little is known about its involvement in glial activation. To explore the functional role of C/EBPbeta in glial activation we have analyzed pro-inflammatory gene expression and neurotoxicity in murine wild type and C/EBPbeta-null glial cultures. METHODS: Due to fertility and mortality problems associated with the C/EBPbeta-null genotype we developed a protocol to prepare mixed glial cultures from cerebral cortex of a single mouse embryo with high yield. Wild-type and C/EBPbeta-null glial cultures were compared in terms of total cell density by Hoechst-33258 staining; microglial content by CD11b immunocytochemistry; astroglial content by GFAP western blot; gene expression by quantitative real-time PCR, western blot, immunocytochemistry and Griess reaction; and microglial neurotoxicity by estimating MAP2 content in neuronal/microglial cocultures. C/EBPbeta DNA binding activity was evaluated by electrophoretic mobility shift assay and quantitative chromatin immunoprecipitation. RESULTS: C/EBPbeta mRNA and protein levels, as well as DNA binding, were increased in glial cultures by treatment with lipopolysaccharide (LPS) or LPS + interferon gamma (IFNgamma). Quantitative chromatin immunoprecipitation showed binding of C/EBPbeta to pro-inflammatory gene promoters in glial activation in a stimulus- and gene-dependent manner. In agreement with these results, LPS and LPS+IFNgamma induced different transcriptional patterns between pro-inflammatory cytokines and NO synthase-2 genes. Furthermore, the expressions of IL-1beta and NO synthase-2, and consequent NO production, were reduced in the absence of C/EBPbeta. In addition, neurotoxicity elicited by LPS+IFNgamma-treated microglia co-cultured with neurons was completely abolished by the absence of C/EBPbeta in microglia. CONCLUSIONS: These findings show involvement of C/EBPbeta in the regulation of pro inflammatory gene expression in glial activation, and demonstrate for the first time a key role for C/EBPbeta in the induction of neurotoxic effects by activated microglia. PMID- 22074463 TI - Injuries associated with housing conditions in Europe: a burden of disease study based on 2004 injury data. AB - BACKGROUND: The authors recently undertook a study for the World Health Organization estimating the European burden of injuries that can be attributed to remediable structural hazards in the home. Such estimates are essential for motivating injury prevention efforts as they quantify potential health gains, in terms of injuries prevented, via specific environmental interventions. METHODS: We combined exposure estimates from existing surveys and scenarios with estimates of the exposure-risk relationship obtained from a structured review of the literature on injury in the home and housing conditions. The resulting attributable fractions were applied to burden of injury data for the WHO European Region. RESULTS: This analysis estimated that two specific hazards, lack of window guards at second level and higher, and lack of domestic smoke detectors resulted in an estimated 7,500 deaths and 200,000 disability adjusted life years (DALYs) per year. In estimating the environmental burden of injury associated with housing, important deficiencies in injury surveillance data and related limitations in studies of injury risk attributable to the home environment were apparent. The ability to attribute proportions of the home injury burden to features of the home were correspondingly limited, leading to probable severe underestimates of the burden. CONCLUSIONS: The burden of injury from modifiable home injury exposures is substantial. Estimating this burden in a comprehensive and accurate manner requires improvements to the scope of injury surveillance data and the evidence base regarding the effectiveness of interventions. PMID- 22074464 TI - Comparison of higher order aberrations after implantable Collamer Lens implantation and wavefront-guided LASEK in high myopia. AB - PURPOSE: To compare changes in ocular higher order aberrations (HOAs) after Visian Implantable Collamer Lens (ICL, STAAR Surgical Co) implantation and wavefront-guided laser epithelial keratomileusis (WFG-LASEK) to correct high myopia. METHODS: This prospective case series comprised 30 eyes (18 patients) that underwent ICL implantation (ICL group) and 33 eyes (18 patients) that underwent WFG-LASEK (WFG-LASEK group). All eyes had spherical equivalent of -6.00 to -9.00 diopters. Entire ocular, internal optic, and corneal HOAs were measured before surgery and 3 months after surgery using a laser ray tracing aberrometer. Contrast sensitivity testing was performed in 10 eyes from each group at a photopic light level of 85 cd/m(2) and a mesopic level of 3 cd/m(2) 3 months after surgery. RESULTS: In the ICL group, HOAs changed for the entire ocular trefoil-y, spherical aberration, internal optic spherical aberration, and corneal trefoil-y. In the WFG-LASEK group, increased HOAs were observed for total HOAs, entire ocular and corneal spherical aberration, secondary astigmatism, and tetrafoil. The ICL group had lower induced aberration values of entire ocular and corneal HOAs compared with the WFG-LASEK group. No significant differences in contrast sensitivity values between groups at the photopic level were noted; however, contrast sensitivity values were significantly lower for 3 (P=.01) and 6 cycles per degree (P<.001) in the WFG-LASEK group at the mesopic level. At the mesopic level, total HOAs, trefoil-y, spherical aberration, and secondary astigmatism were higher in the WFG-LASEK group. CONCLUSIONS: Implantable Collamer Lens implantation induced fewer ocular and corneal HOAs and resulted in better contrast sensitivity at mesopic levels than WFG-LASEK in eyes with high myopia. PMID- 22074465 TI - Inadvertent LASIK flap creation over a soft contact lens. AB - PURPOSE: To report the findings and outcomes in two cases in which a contact lens was inadvertently present during creation of a LASIK corneal flap. METHODS: Interventional case report. RESULTS: A soft contact lens blocked the successful creation of the corneal flap with a femtosecond laser in one patient. Repeat surgery 1 week later resulted in a normal flap. In the second patient, a thin but normal-shaped flap was successfully created using a microkeratome despite the presence of a soft contact lens in the patient's eye. No adverse effect on vision was noted in either case. CONCLUSIONS: Refractive surgeons are encouraged to establish or review current procedures to ensure adequate contact lens removal prior to LASIK surgery, as it may result in an aborted procedure or a potentially thin and/or irregular corneal flap. PMID- 22074466 TI - Theoretical performance of intraocular lenses correcting both spherical and chromatic aberration. AB - PURPOSE: To assess the performance and optical limitations of intraocular lenses (IOLs) correcting both longitudinal spherical aberration (LSA) and longitudinal chromatic aberration (LCA) compared to standard spherical and aspheric IOLs. METHODS: Using a set of 46 white light, pseudophakic eye models representing a population of cataract patients, retinal image quality was assessed for three IOL designs-standard spherical IOLs; aspheric IOLs, correcting a fixed amount of LSA; and aspheric refractive/diffractive IOLs, correcting a fixed amount of LSA and LCA. Depth of field and tolerance to IOL misalignments were also assessed. RESULTS: The improvement factor, based on the area under the radial polychromatic modulation transfer function (pMTF) curve of the IOL, correcting both average LSA and LCA over the aspheric IOL was 1.19+/-0.12, and over the spherical IOL was 1.43+/-0.29. Within the range of +/-1.00 diopter of defocus, pMTF of the IOL correcting both LSA and LCA was equal or higher than both the spherical and aspheric IOLs. The IOL could be decentered up to 0.6 to 0.8 mm before the performance degraded below that of a spherical IOL. CONCLUSIONS: This is the first study that evaluates IOLs correcting both LSA and LCA in the presence of corneal higher order aberrations. Intraocular lenses that correct both LSA and LCA improve simulated retinal image quality over spherical IOLs and IOLs that correct LSA alone, without sacrificing depth of field or tolerance to decentration. Correction of LCA in combination with LSA shows the potential to improve visual performance. PMID- 22074467 TI - Intracorneal ring segments implantation followed by same-day photorefractive keratectomy and corneal collagen cross-linking in keratoconus. AB - PURPOSE: To evaluate the efficacy of intrastromal corneal ring segments implantation followed by same-day photorefractive keratectomy (PRK) and ultraviolet-A/riboflavin collagen cross-linking (CXL) in patients with keratoconus. METHODS: Four patients (five eyes) were included in the study. All patients first underwent femtosecond laser-enabled placement of intracorneal ring segments (Intacs, Addition Technology). Uncorrected (UDVA) and corrected distance visual acuity (CDVA) and keratometry readings remained stable for 6 months. Same day PRK and CXL were subsequently performed in all patients. RESULTS: Six months after Intacs plus PRK/CXL, significant improvements were noted for UDVA, CDVA, spherical equivalent refraction, keratometry, and total aberrations. No patient lost lines of CDVA or developed haze. CONCLUSIONS: The combination of intracorneal ring segments implantation followed by sequential same-day PRK/CXL may be a reasonable option for improving visual acuity in select patients with keratoconus. PMID- 22074468 TI - Migration, social mobility and common mental disorders: critical review of the literature and meta-analysis. AB - OBJECTIVE: Changes in socio-economic position in people who migrate may have adverse associations with mental health. The main objective of this review was to assess the association of social mobility with common mental disorders in migrant and second-generation groups, to inform future research. DESIGN: Systematic review and meta-analysis of English-language studies assessing the association of social mobility in migrant or second-generation groups with common mental disorders. Approaches to operationalise 'social mobility' were reviewed. RESULTS: Twelve studies (n=18,548) met criteria for retrieval. Very few included second generation groups, and most studies were cross-sectional in design. Approaches to operationalise 'social mobility' varied between studies. Downward intragenerational social mobility was associated with migration in the majority of studies. Random effects meta-analysis (n=5179) suggested that migrants to higher income countries who experienced downward mobility or underemployment were more likely to screen positive for common mental disorders, relative to migrants who were upwardly mobile or experienced no changes to socio-economic position. Conclusions on second-generation groups were limited by the lack of research highlighted for these groups. Downward intragenerational mobility associated with migration may be associated with vulnerability to common mental disorders in some migrant groups. CONCLUSION: Given the increasing scale of global migration, further research is needed to clarify how changes to socio-economic position associated with international migration may impact on the mental health of migrants, and in their children. PMID- 22074469 TI - EphrinA5 suppresses colon cancer development by negatively regulating epidermal growth factor receptor stability. AB - Colon cancer is one of the most common human cancers worldwide. Owing to its aggressiveness and lethality, it is necessary to determine the mechanisms regulating the carcinogenesis of colon cancer. EphrinA5 has been reported to act as a putative tumor suppressor in glioma; however, little is known concerning the role of this protein in the context of colon cancer. To elucidate the biological significance of ephrinA5 in colon cancer, we examined ephrinA5 and epidermal growth factor receptor (EGFR) expression profiles in both colon cancer and normal tissues, using immunohistochemistry on a 96-spot tissue microarray. Gain-of function and loss-of-function experiments were performed on the human colon cancer cell lines SW480 and WiDr to determine the biological effects of ephrinA5 in relation to cell proliferation, survival, and migration. It was found that ephrinA5 mRNA and protein levels were significantly reduced in colon cancer as compared with normal colon tissue specimens. EphrinA5 expression was also negatively associated with tumor differentiation and clinical stage. In colon cancer cell line models, ephrinA5 exerted an inhibitory effect on EGFR by promoting c-Cbl-mediated EGFR ubiquitination and degradation. EphrinA5 did not affect the transcriptional regulation of EGFR mRNA expression in colon cancer cells. Expression of ephrinA5 suppressed colon cancer cell proliferation, migration, and chemotherapeutic resistance. In conclusion, ephrinA5 inhibited colon cancer progression by promoting c-Cbl-mediated EGFR degradation. Our findings identify a novel mechanism that could be utilized to improve the therapeutic efficiency of EGFR-targeting strategies. PMID- 22074470 TI - European veterinary dissertations. PMID- 22074471 TI - Inferring semantic organization from refractory access dysphasia: further replication in the domains of geography and proper nouns but not concrete and abstract concepts. AB - Patients with "refractory access dysphasia" have been a source of unique insight into the organization of previously unexplored domains of semantic knowledge (i.e., proper nouns, geography, concrete and abstract concepts). However, much of the relevant data have been based on the performance of a small number of patients. Here, we present 2 patients who both display a "refractory access" pattern of performance on spoken-word-written-word matching tasks and test their performance in the domains of famous people, geography, and abstract and concrete words. While these patients show performance similar to that for the previously reported patients in the domains of famous people and geography, they show a very different pattern of performance with abstract and concrete nouns. We discuss possible reasons why patients may differ in performance and evidence for and against the "differential frameworks" hypothesis for the organization of concrete and abstract concepts. PMID- 22074472 TI - Face recognition impairments despite normal holistic processing and face space coding: evidence from a case of developmental prosopagnosia. AB - Holistic processing and face space coding are widely considered primary perceptual mechanisms behind good face recognition. Here, however, we present the case of S.P., a developmental prosopagnosic who demonstrated severe impairments in face memory and face perception, yet showed normal holistic processing and face space coding. Across three composite experiments, S.P. showed normal strength holistic processing for upright faces and no composite effect for inverted faces. Across five aftereffect experiments, S.P. showed normal-sized face aftereffects, which derived normally from face space rather than shape generic mechanisms. The case of S.P. implies: (a) normal holistic processing and face space coding can be insufficient for good face recognition even when present in combination; and (b) the focus of recent literature on holistic processing and face space should be expanded to include other potential face processing mechanisms (e.g., part-based processing). Our article also highlights the importance of internal task reliability in drawing inferences from single-case studies. PMID- 22074477 TI - Incorporation of positively charged linkages into DNA and RNA backbones: a novel strategy for antigene and antisense agents. PMID- 22074478 TI - Visualising neuroinflammation in post-stroke patients: a comparative PET study with the TSPO molecular imaging biomarkers [11C]PK11195 and [11C]vinpocetine. AB - With the main objective of comparing the prospective diagnostic power of two 11C labelled molecular imaging biomarkers with affinity for TSPO and used for the visualisation of activated microglia after a stroke, we measured with positron emission tomography (PET) in four post-stroke patients the regional brain uptake and binding potential of [11C]vinpocetine and [11C]PK11195. Percentage standard uptake values (%SUV) and binding potential (BPND) were used as outcome measures. The total peak brain uptake value and average global brain uptake value were higher for [11C]vinpocetine than for [11C]PK11195. The regional %SUV values were significantly higher for [11C]vinpocetine than for [11C]PK11195 in the hemispheres as well as in almost all standard brain regions. The %SUV values of [11C]vinpocetine were higher in the peri-infarct zone than in the ischaemic core, however, the difference did not prove to be significant. There was basically no difference in %SUV values between the ischaemic core and the peri-infarct zone for [11C]PK11195. The BPND values for [11C]vinpocetine were higher in all standard regions than those for [11C]PK11195, but the difference was not significant between them. The BPND values of [11C]vinpocetine were higher in the peri-infarct zone than in the ischaemic core, however, the difference did not prove to be significant. A comparative analysis of the two ligands indicates that [11C]vinpocetine shows a number of favourable characteristics over [11C]PK11195, but to demonstrate that it may serve as a prospective molecular imaging biomarker of microglia activation in post-stroke patients, further studies are required. PMID- 22074479 TI - Epidermal growth factor receptors: a functional perspective. AB - The epidermal growth factor receptors (EGFRs) belong to the ErbB family of receptor tyrosine kinases (TKs) involved in the proliferation of normal and malignant cells. EGFR has attracted considerable attention as a target for cancer therapy. This article considers various functional roles of EGFR-based systems that are relevant for the early detection and staging of cancers overexpressing EGFR. PMID- 22074480 TI - Synthesis of 99mTc-nimotuzumab with tricarbonyl ion: in vitro and in vivo studies. AB - The Epidermal growth factor receptor (EGFR) family plays an important role in carcinogenesis. CIMAher(r) (Nimotuzumab), is a humanized monoclonal antibody, which recognizes EGFR with high affinity. The aim of this work was to perform the direct labeling of Nimotuzumab with [99mTc(CO)3(H2O)3]+ as precursor and to evaluate its labeling conditions, in vitro and in vivo stability and biodistrution in normal C57 BL/6J mice. 99mTc(CO3)-Nimotuzumab labeling yields were up to 90%. More than 90% of the complex remained intact after 24 h of incubation with L-Histidine (1/300 molar ratio). Biodistribution studies in normal mice were also performed. Inmunoreactivity was confirmed by cell binding assays with A431cells. These results encourage the evaluation of the potential role of 99mTc(CO)3-Nimotuzumab as a novel tumor-avid radiotracer for targeting in vivo EGFR expression. PMID- 22074481 TI - (68)Ga-Citrate-PET for diagnostic imaging of infection in rats and for intra abdominal infection in a patient. AB - OBJECTIVES: 67Ga-Citrate has been extensively used for infection and inflammation imaging for the past four decades but has limitations. In the present study, we explored the ability of 68Ga-Citrate to detect Staphylococcus aureus (Staph A) infection in rats and further studied its ability to localize intra-abdominal infection in a patient. METHODS: An infection was induced in male Wistar rats by injecting Staph A in the right thigh muscle. In this study a simple method was described for the preparation of 68Ga-Citrate with > 99% yield and purity. 68Ga Citrate (15 MBq/rat and 150 MBq/patient) was injected intravenously and the images were acquired for 10 min each. RESULTS: 68Ga-Citrate uptake was moderate at the infection lesion within 5 min post injection but intense focal uptake was visualized from 30 min to 6 hr post-injection in rats. Cardiac blood pool and liver activity decreased during the same period of study. In the patient studied, an infected area in the abdomen at the site of recent appendectomy was detected within 30min post-injection of 68Ga-Citrate, which was consistent with CT and microbiology findings. CONCLUSION: A simple method of preparation of 68Ga-Citrate with > 99% yield and purity was described, suitable for routine clinical work. Our results showed 68Ga-Citrate is capable of detecting Staph A infection in rats and an intraabdominal infection in a post-operative patient. These findings indicate the high potential of 68Ga-Citrate for clinical utility. PMID- 22074482 TI - Generation of subject-specific, dynamic, multisegment ankle and foot models to improve orthotic design: a feasibility study. AB - BACKGROUND: Currently, custom foot and ankle orthosis prescription and design tend to be based on traditional techniques, which can result in devices which vary greatly between clinicians and repeat prescription. The use of computational models of the foot may give further insight in the biomechanical effects of these devices and allow a more standardised approach to be taken to their design, however due to the complexity of the foot the models must be highly detailed and dynamic. METHODS/DESIGN: Functional and anatomical datasets will be collected in a multicentre study from 10 healthy participants and 15 patients requiring orthotic devices. The patient group will include individuals with metarsalgia, flexible flat foot and drop foot.Each participant will undergo a clinical foot function assessment, 3D surface scans of the foot under different loading conditions, and detailed gait analysis including kinematic, kinetic, muscle activity and plantar pressure measurements in both barefoot and shod conditions. Following this each participant will undergo computed tomography (CT) imaging of their foot and ankle under a range of loads and positions while plantar pressures are recorded. A further subgroup of participants will undergo magnetic resonance imaging (MRI) of the foot and ankle.Imaging data will be segmented to derive the geometry of the bones and the orientation of the joint axes. Insertion points of muscles and ligaments will be determined from the MRI and CT-scans and soft tissue material properties computed from the loaded CT data in combination with the plantar pressure measurements. Gait analysis data will be used to drive the models and in combination with the 3D surface scans for scaling purposes. Predicted plantar pressures and muscle activation patterns predicted from the models will be compared to determine the validity of the models. DISCUSSION: This protocol will lead to the generation of unique datasets which will be used to develop linked inverse dynamic and forward dynamic biomechanical foot models. These models may be beneficial in predicting the effect of and thus improving the efficacy of orthotic devices for the foot and ankle. PMID- 22074484 TI - IDH1 mutations are not found in cartilaginous tumours other than central and periosteal chondrosarcomas and enchondromas. PMID- 22074483 TI - MiRNA expression patterns predict survival in glioblastoma. AB - BACKGROUND: In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. METHODS: 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom(r) Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. RESULTS: It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. CONCLUSIONS: At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required. PMID- 22074485 TI - Microglia use multiple mechanisms to mediate interactions with vitronectin; non essential roles for the highly-expressed alphavbeta3 and alphavbeta5 integrins. AB - BACKGROUND: As the primary resident immune cells, microglia play a central role in regulating inflammatory processes in the CNS. The extracellular matrix (ECM) protein vitronectin promotes microglial activation, switching microglia into an activated phenotype. We have shown previously that microglia express two vitronectin receptors, alphavbeta3 and alphavbeta5 integrins. As these integrins have well-defined roles in activation and phagocytic processes in other cell types, the purpose of the current study was to investigate the contribution of these two integrins in microglial activation. METHODS: Microglial cells were prepared from wild-type, beta3 integrin knockout (KO), beta5 integrin KO or beta3/beta5 integrin DKO mice, and their interactions and activation responses to vitronectin examined in a battery of assays, including adhesion, expression of activation markers, MMP-9 expression, and phagocytosis. Expression of other alphav integrins was examined by flow cytometry and immunoprecipitation. RESULTS: Surprisingly, when cultured on vitronectin, microglia from the different knockout strains showed no obvious defects in adhesion, activation marker expression, MMP 9 induction, or phagocytosis of vitronectin-coated beads. To investigate the reason for this lack of effect, we examined the expression of other alphav integrins. Flow cytometry showed that beta3/beta5 integrin DKO microglia expressed residual alphav integrin at the cell surface, and immunoprecipitation confirmed this finding by revealing the presence of low levels of the alphavbeta1 and alphavbeta8 integrins. beta1 integrin blockade had no impact on adhesion of beta3/beta5 integrin DKO microglia to vitronectin, suggesting that in addition to alphavbeta1, alphavbeta3, and alphavbeta5, alphavbeta8 also serves as a functional vitronectin receptor on microglia. CONCLUSIONS: Taken together, this demonstrates that the alphavbeta3 and alphavbeta5 integrins are not essential for mediating microglial activation responses to vitronectin, but that microglia use multiple redundant receptors to mediate interactions with this ECM protein. PMID- 22074486 TI - Determining transport efficiency for the purpose of counting and sizing nanoparticles via single particle inductively coupled plasma mass spectrometry. AB - Currently there are few ideal methods for the characterization of nanoparticles in complex, environmental samples, leading to significant gaps in toxicity and exposure assessments of nanomaterials. Single particle-inductively coupled plasma mass spectrometry (spICPMS) is an emerging technique that can both size and count metal-containing nanoparticles. A major benefit of the spICPMS method is its ability to characterize nanoparticles at concentrations relevant to the environment. This paper presents a practical guide on how to count and size nanoparticles using spICPMS. Different methods are investigated for measuring transport efficiency (i.e., nebulization efficiency), an important term in the spICPMS calculations. In addition, an alternative protocol is provided for determining particle size that broadens the applicability of the technique to all types of inorganic nanoparticles. Initial comparison, using well-characterized, monodisperse silver nanoparticles, showed the importance of having an accurate transport efficiency value when determining particle number concentration and, if using the newly presented protocol, particle size. Ultimately, the goal of this paper is to provide improvements to nanometrology by further developing this technique for the characterization of metal-containing nanoparticles. PMID- 22074487 TI - Conservation and loss of ribosomal RNA gene sites in diploid and polyploid Fragaria (Rosaceae). AB - BACKGROUND: The genus Fragaria comprises species at ploidy levels ranging from diploid (2n = 2x = 14) to decaploid (2n = 10x = 70). Fluorescence in situ hybridization with 5S and 25S rDNA probes was performed to gather cytogenetic information that illuminates genomic divergence among different taxa at multiple ploidy levels, as well as to explore the evolution of ribosomal RNA genes during polyploidization in Fragaria. RESULTS: Root tip cells of diploid taxa were typified by two 5S and six 25S rDNA hybridization signals of varying intensities, providing a baseline for comparisons within the genus. In three exceptional diploid genotypes, F. nilgerrensis (CFRA 1358 and CFRA 1825) and F. vesca 'Yellow Wonder', two 5S but only four 25S rDNA sites were found but with differing site losses. The numbers of 5S and 25S rDNA signals, respectively were three and nine in a triploid F. *bifera accession, and were four and twelve in three tetraploids, thus occurring in proportional 1.5* and 2* multiples of the typical diploid pattern. In hexaploid F. moschata, a proportional multiple of six 5S rDNA sites was observed, but the number of 25S rDNA sites was one or two less than the proportionate prediction of eighteen. This apparent tendency toward rDNA site loss at higher ploidy was markedly expanded in octoploids, which displayed only two 5S and ten 25S rDNA sites. In the two decaploids examined, the numbers of 5S and 25S rDNA signals, respectively, were four and fifteen in F. virginiana subsp. platypetala, and six and twelve in F. iturupensis. CONCLUSIONS: Among diploid Fragaria species, a general consistency of rDNA site numbers implies conserved genomic organization, but highly variable 25S signal sizes and intensities and two instances of site loss suggest concurrent high dynamics of rDNA copy numbers among both homologs and non-homologs. General conservation of rDNA site numbers in lower ploidy, but marked site number reductions at higher ploidy levels, suggest complex evolution of rDNA sites during polyploidization and/or independent evolutionary pathways for 6x versus higher ploidy strawberries. Site number comparisons suggest common genomic composition among natural octoploids, and independent origins of the two divergent decaploid accessions. PMID- 22074488 TI - Sleep-related groaning: prevalence and characteristics in a cohort of patients with suspected obstructive sleep apnea. AB - CONCLUSION: Nocturnal groaning has the same prevalence in patients referred for diagnosis of sleep-disordered breathing as among other populations referred for sleep studies. The respiratory tracings in these patients have a distinct appearance that is possible to recognize with a polygraphic recording and thereby prevent the pattern from being misdiagnosed as central apneas. OBJECTIVES: The aim of this study was first to estimate the prevalence of groaning in patients referred for diagnosis of sleep-related breathing disorders. Second, we wanted to describe the respiratory pattern in order to distinguish the patients from patients with sleep apnea. METHODS: This was a prospective study in 1004 patients, performed in the Sleep Unit in our ENT Department, during a 12 month period. RESULTS: Four patients were diagnosed with video polysomnography, and the diagnosis of nocturnal groaning was confirmed. The prevalence of groaning in our sleep laboratory was 0.4%. All the patients had a mild form of sleep-related disturbance, and all groaning episodes occurred during REM sleep. The groaning events appeared in clusters. The length of each groan varied between 4 and 38 s. The number of events in a period varied between 2 and 11, and the length of each groaning period ranged between 11 and 168 s. PMID- 22074490 TI - Anti-Shiga toxin immunoglobulin G antibodies in healthy South Korean slaughterhouse workers. AB - BACKGROUND: Slaughterhouse workers are in direct contact with cattle nearly every day. The purpose of this study was to survey the presence and distribution of anti-Shiga toxin 1 (Stx1) immunoglobulin G (IgG) in slaughterhouse workers, enabling a study of the serologic response to this toxin while working in an area at high-risk of Stx-producing Escherichia coli (STEC) infection. METHODS: One thousand seven hundred and twenty-nine serum samples from healthy slaughterhouse employees were collected and surveyed by indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: Among the 5 slaughterhouse positions, slaughterers had the highest distribution of anti-Stx1 IgG values by an ELISA. Based on the ELISA values, 25% (433/1729) of the workers had anti-Stx1 IgG. Slaughterers, residual products handlers, inspectors, livestock hygiene controllers, and grading testers had anti-Stx1 IgG-positive rates of 28%, 25%, 20%, 19%, and 17%, respectively. The ELISA values of anti-Stx1 IgG increased with increases in the number of years worked by slaughterers, but not by residual products handlers, inspectors, livestock hygiene controllers, or grading testers. CONCLUSIONS: From these results, slaughterhouse workers are healthy and asymptomatic; slaughterers in particular are at high-risk for STEC exposure. PMID- 22074491 TI - Mental health promotion of Iranian university students: the effect of self-esteem and health locus of control. AB - The purpose of this study was to investigate the effect of self-esteem and health control belief on promoting students' mental health. In so doing, 144 students from two medical universities in the north-east of Iran were recruited into study. They were pair-matched and randomly assigned to case and control groups. The data were collected through Goldberg's General Health Questionnaire-28, Multidimensional Health Locus of Control and Rosenberg's Self-Esteem Scales. The results showed that there were significant differences between the groups before and after the intervention. The external components of health locus of control (chance and powerful others) showed a significant decrease but the internal health locus of control and self-esteem revealed a significant increase after the intervention (P < 0.0001). Moreover, the students' mental health had a significant increase after 3 months of intervention (P < 0.0001). The findings emphasize that the programme can improve the health locus of control beliefs, self-esteem and mental health promotion of the students. This will require additional monitoring and uninterrupted attempts to be effective. PMID- 22074492 TI - Rationally designed phthalocyanines having their main absorption band beyond 1000 nm. AB - Highly air-stable phthalocyanines (Pcs) having their main absorption band beyond 1000 nm have been synthesized using main-group elements as peripheral and central (core) substituents. The resultant [(PhS)(8)PcP(OMe)(2)][PF(6)] and [(PhSe)(8)PcP(OMe)(2)][PF(6)] show a single Q-band peak at 1018 and 1033 nm, respectively, which was achieved by carefully taking into account the spectroscopic properties of Pcs and the characteristics of the frontier orbitals. The large red shift can be considered to originate from synergistic effects involving both the group-15 and -16 elements. PMID- 22074494 TI - Developmental validation of the AmpFlSTR(r) Identifiler(r) Plus PCR Amplification Kit: an established multiplex assay with improved performance. AB - Analysis of length polymorphism at short tandem repeat (STR) loci utilizing multiplex polymerase chain reaction (PCR) remains the primary method for genotyping forensic samples. The AmpFlSTR((r)) Identifiler((r)) Plus PCR Amplification Kit is an improved version of the AmpFlSTR((r)) Identifiler((r)) PCR Amplification Kit and amplifies the core CODIS loci: D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, CSF1PO, FGA, TH01, TPOX, and vWA. Additional loci amplified in the multiplex reaction are the sex-determinant, amelogenin, and two internationally accepted loci, D2S1338 and D19S433. While the primer sequences and dye configurations were unchanged, the AmpFlSTR((r)) Identifiler((r)) Plus PCR Amplification Kit features an enhanced buffer formulation and an optimized PCR cycling protocol that increases sensitivity, provides better tolerance to PCR inhibitors, and improves performance on mixture samples. The AmpFlSTR((r)) Identifiler((r)) Plus PCR Amplification Kit has been validated according to the FBI/National Standards and Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. The validation results support the use of the AmpFlSTR((r)) Identifiler((r)) Plus PCR Amplification Kit for human identity and parentage testing. PMID- 22074495 TI - Targeting notch pathway enhances rapamycin antitumor activity in pancreas cancers through PTEN phosphorylation. AB - BACKGROUND: Pancreas cancer is one of most aggressive human cancers with the survival rate for patients with metastatic pancreas cancer at 5-6 months. The poor survival demonstrates a clear need for better target identification, drug development and new therapeutic strategies. Recent discoveries have shown that the role for Notch pathway is important in both development and cancer. Its contribution to oncogenesis also involves crosstalks with other growth factor pathways, such as Akt and its modulator, PTEN. The mounting evidence supporting a role for Notch in cancer promotion and survival suggests that targeting this pathway alone or in combination with other therapeutics represents a promising therapeutic strategy. RESULTS: Using a pancreas cancer tissue microarray, we noted that Jagged1, Notch3 and Notch4 are overexpressed in pancreas tumors (26%, 84% and 31% respectively), whereas Notch1 is expressed in blood vessels. While there was no correlation between Notch receptor expression and survival, stage or tumor grade, Notch3 was associated with Jagged1 and EGFR expression, suggesting a unique relationship between Notch3 and Jagged1. Inhibition of the Notch pathway genetically and with gamma-secretase inhibitor (GSI) resulted in tumor suppression and enhanced cell death. The observed anti-tumor activity appeared to be through Akt and modulation of PTEN phosphorylation. We discovered that transcriptional regulation of RhoA by Notch is important for PTEN phosphorylation. Finally, the mTOR inhibitor Rapamycin enhanced the effect of GSI on RhoA expression, resulting in down regulation of phospho-Akt and increased in vitro tumor cytotoxity. CONCLUSIONS: Notch pathway plays an important role in maintaining pancreas tumor phenotype. Targeting this pathway represents a reasonable strategy for the treatment of pancreas cancers. Notch modulates the Akt pathway through regulation of PTEN phosphorylation, an observation that has not been made previously. Furthermore, we discovered that this regulation is dependent on RhoA/Rock1 activation. Enhanced phospho-Akt suppression when GSI is combined with rapamycin suggests that targeting both pathways will lead to a greater efficacy in the treatment of patients with pancreas cancer. PMID- 22074496 TI - Tandem one-pot synthesis of polysubstituted pyridines using the Blaise reaction intermediate and 1,3-enynes. AB - A tandem one-pot method for the construction of a pyridine moiety with selective control of substitution patterns has been developed through the sequential reactions of nitrile with a Reformatsky reagent and 1,3-enyne involving regio- and chemoselective addition of the Blaise reaction intermediate to 1,3-enyne, followed by isomerization, cyclization, and an aromatization cascade. PMID- 22074498 TI - Molecular dynamics study on the effect of Lewis acid centers in poly(ethylene oxide)/LiClO4 polymer electrolyte. AB - Molecular dynamics simulations employing a polarizable force field have been performed for the model poly(ethylene oxide)/LiClO(4) electrolytes with boron or aluminum centers. Influence of Lewis acid centers on radial distribution functions, coordination numbers, percentage of free cations, diffusion coefficients and conductivity has been investigated. Results confirm the effect of acid centers on ion complexation and show that the properties of the electrolyte result from interplay of different interactions. PMID- 22074499 TI - Topical antiseptics in wound care: time for reflection. PMID- 22074497 TI - Changes in neuromuscular transmission in the W/W(v) mouse internal anal sphincter. AB - BACKGROUND: Intramuscular interstitial cells of Cajal (ICC-IM) have been shown to participate in nitrergic neuromuscular transmission (NMT) in various regions of the gastrointestinal (GI) tract, but their role in the internal anal sphincter (IAS) is still uncertain. Contractile studies of the IAS in the W/W(v) mouse (a model in which ICC-IM numbers are markedly reduced) have reported that nitrergic NMT persists and that ICC-IM are not required. However, neither the changes in electrical events underlying NMT nor the contributions of other non-nitrergic neural pathways have been examined in this model. METHODS: The role of ICC-IM in NMT was examined by recording the contractile and electrical events associated with electrical field stimulation (EFS) of motor neurons in the IAS of wildtype and W/W(v) mice. Nitrergic, purinergic, and cholinergic components were identified using inhibitors of these pathways. KEY RESULTS: Under NANC conditions, purinergic and nitrergic pathways both contribute to EFS-induced inhibitory junction potentials (IJPs) and relaxation. Purinergic IJPs and relaxation were intact in the W/W(v) mouse IAS, whereas nitrergic IJPs were reduced by 50-60% while relaxation persisted. In the presence of L-NNA (NOS inhibitor) and MRS2500 (P2Y1 receptor antagonist), EFS gave rise to cholinergic depolarization and contractions that were abolished by atropine. Cholinergic depolarization was absent in the W/W(v) mouse IAS while contraction persisted. CONCLUSIONS & INFERENCES: ICC-IM significantly contributes to the electrical events underlying nitrergic and cholinergic NMT, whereas contractile events persist in the absence of ICC-IM. The purinergic inhibitory neural pathway appears to be independent of ICC-IM. PMID- 22074504 TI - Preface. PMID- 22074505 TI - Gastrointestinal surgery II. PMID- 22074503 TI - Bioactive compounds from endemic plants of Southwest Portugal: inhibition of acetylcholinesterase and radical scavenging activities. AB - CONTEXT: Natural products are reported to have substantial neuroprotective activity due to their radical scavenging capacity, and also acetylcholinesterase (AChE) inhibitory capacity, both activities important in neurodegeneration. OBJECTIVE: The undesirable side effects of compounds in pharmacological use make it important to identify natural neuroprotective molecules. This work assesses the potential of five endemic Portuguese plants as sources of neuroprotective compounds. MATERIALS AND METHODS: Antioxidant capacity for peroxyl radical was determined by Oxygen Radical Absorbance Capacity method and for hydroxyl by Electron Paramagnetic Resonance, as well as AChE inhibitory capacity of the plant hydroethanolic extracts. The molecules responsible for these valuable properties were also tentatively identified by HPLC. RESULTS AND DISCUSSION: Armeria rouyana and Thymus capitellatus presented some of the highest phenolic contents (76.60 +/ 7.19 and 12.82 +/- 0.24 mg GAE g-1 dw, respectively) and antioxidant capacities (592 +/- 116 and 449 +/- 57 MUmol TE g-1 dw, respectively). The flavonoids were identified as the phytomolecules related to the antioxidant capacity of these plant extracts; in the case of A. rouyana, l-ascorbic acid also made an important contribution (3.27 +/- 0.26 mg g-1 dw). Plant extracts clearly demonstrated effective AChE inhibitory activity (480 +/- 98 and 490 +/- 46 MUg mL-1, respectively), that could be associated to polyphenols. CONCLUSIONS: The extracts of A. rouyana and T. capitellatus and their active components, especially polyphenols, demonstrate interesting neuroprotective potential. They, therefore, deserve further study as their phytomolecules are promising sources of either natural neuroprotective products and/or novel lead compounds. PMID- 22074507 TI - Therapy of cervical, thoracic, and lumbar spinal cord problems. PMID- 22074506 TI - The external skeletal fixation system: IM PINS, wire, and external skeletal fixator. PMID- 22074508 TI - Urinary incontinence. PMID- 22074509 TI - Periodontal disease: An update. PMID- 22074510 TI - Field trials with Vedaprofen, a new non-steroidal anti-inflammatory drug. PMID- 22074511 TI - Topical carbonic anhydrase inhibitors in the treatment of glaucoma. PMID- 22074512 TI - Veterinary bolted pinning or interlocking nail: Clinical study of 45 cases. PMID- 22074513 TI - Two failed urethrostomy procedures in one cat. PMID- 22074514 TI - Treatment of diabetes mellitus in dogs and cats. PMID- 22074515 TI - Diagnosis and treatment of canine hypothyroidism. PMID- 22074516 TI - Drug-food interactions in cardiac patients. PMID- 22074518 TI - Canine dilated cardiomyopathy: A study of 189 cases in 38 breeds. PMID- 22074517 TI - Diagnosis and management of small bowel diarrhea. PMID- 22074519 TI - Primary hyperparathyroidism in a cat: A case report. PMID- 22074520 TI - Urinary corticoid/creatinine ratio in dogs with hyperadrenocorticism. PMID- 22074521 TI - Ascites due to persistent eustachian valves in a young golden retriever. PMID- 22074522 TI - Hypocalcemia due to hypoparathyroidism in a dog. PMID- 22074523 TI - Feline leukemia virus & feline immunodeficiency virus. PMID- 22074524 TI - Feline infectious peritonitis-new insights. PMID- 22074525 TI - Diagnosis and control of gastrointestinal parasites in dogs and cats. PMID- 22074526 TI - Epidemiology and control of fleas infesting dogs and cats. PMID- 22074527 TI - The role of cats in some important rickettsial diseases of humans in southern Africa. PMID- 22074529 TI - Cytology for the diagnosis of neoplastic and non-neoplastic disease. PMID- 22074528 TI - Atypical mycobacteriosis in a cat. PMID- 22074530 TI - How to successfully use diagnostic cytology in veterinary practice. PMID- 22074531 TI - Endoscopy of the upper airways in dogs and cats. PMID- 22074532 TI - Spinal radiography in dogs and cats. PMID- 22074533 TI - Evaluation of a DNA marker for copper toxicosis in bedlington terriers. PMID- 22074534 TI - Assessment of laboratory tests and test results using data on biological variation. PMID- 22074535 TI - Exophthalmos in dogs: A challenge for diagnostic imaging. PMID- 22074536 TI - A computerized ECG analyzer. PMID- 22074538 TI - The death of companion animals in the Netherlands. PMID- 22074537 TI - Helping during pet loss and bereavement. PMID- 22074539 TI - Injection anesthesia in dogs and cats. PMID- 22074540 TI - Artificial ventilation and monitoring in companion animal anesthesia. PMID- 22074541 TI - Diseases of racing pigeon: An update. PMID- 22074542 TI - Radiation therapy for mast cell tumours in companion animals. PMID- 22074544 TI - Influence of cerebellar malformations on cerebral volume: does it matter? PMID- 22074545 TI - Synthesis of 18-membered open-cage fullerenes through controlled stepwise fullerene skeleton bond cleavage processes and substituent-mediated tuning of the redox potential of open-cage fullerenes. AB - Oxidation of the fullerenediol C(60)(OH)(2)(O)(OAc)(OOtBu)(3) with PhI(OAc)(2) yields the open-cage fullerene derivative C(60)(O)(2)(O)(OAc)(OOtBu)(3)2 with an 11-membered orifice. Compound 2 reacts with aniline to form a new open-cage derivative with a 14-membered orifice, which yields an 18-membered open-cage fullerene derivative upon addition of another molecule of aniline. Two different types of aniline derivatives with either electron-donating or electron withdrawing substituents can be added sequentially, affording an unsymmetrical moiety in the open-cage structure. Reduction potentials of the 18-membered open cage fullerene derivatives can be fine-tuned by changing the substituents on the aniline. The results provide new insights about the mechanism of open-cage reactions of fullerene-mixed peroxide. PMID- 22074546 TI - A parametric method for cumulative incidence modeling with a new four-parameter log-logistic distribution. AB - BACKGROUND: Competing risks, which are particularly encountered in medical studies, are an important topic of concern, and appropriate analyses must be used for these data. One feature of competing risks is the cumulative incidence function, which is modeled in most studies using non- or semi-parametric methods. However, parametric models are required in some cases to ensure maximum efficiency, and to fit various shapes of hazard function. METHODS: We have used the stable distributions family of Hougaard to propose a new four-parameter distribution by extending a two-parameter log-logistic distribution, and carried out a simulation study to compare the cumulative incidence estimated with this distribution with the estimates obtained using a non-parametric method. To test our approach in a practical application, the model was applied to a set of real data on fertility history. CONCLUSIONS: The results of simulation studies showed that the estimated cumulative incidence function was more accurate than non parametric estimates in some settings. Analyses of real data indicated that the proposed distribution showed a much better fit to the data than the other distributions tested. Therefore, the new distribution is recommended for practical applications to parameterize the cumulative incidence function in competing risk settings. PMID- 22074547 TI - Mixed modality treatment planning of accelerated partial breast irradiation: to improve complex dosimetry cases. AB - BACKGROUND: Although 3D-conformal accelerated partial breast irradiation (APBI) is widely used, several questions still remain such as what are the optimal treatment planning modalities. Indeed, some patients may have an unfavorable anatomy and/or inadequate dosimetric constraints could be fulfilled ("complex cases"). In such cases, we wondered which treatment planning modality could be applied to achieve 3D-conformal APBI (2 mini-tangents and an "en face" electron field or non-coplanar photon multiple fields; or a mixed technique combining non coplanar photon multiple fields with an "en face" electron beam). METHODS: From October 2007 to March 2010, 55 patients with pT1N0 breast cancer were enrolled in a phase II APBI trial. Among them, 7 patients were excluded as they were considered as "complex cases". A dosimetric comparison was performed according to the 3 APBI modalities mentioned above and assessed: planning treatment volume (PTV) coverage, PTV/whole breast ratio, lung and heart distance within irradiated field and exposure of organs at risk (OAR). RESULTS: Adequate PTV coverage was obtained with the 3 different treatment planning. Regarding OAR exposure, the "mixed technique" seemed to reduce the volume of non-target breast tissue in 4 cases compared to the other techniques (in only 1 case), with the mean V50% at 44.9% (range, 13.4 - 56.9%) for the mixed modality compared to 51.1% (range, 22.4 - 63.4%) and 51.8% (range, 23.1 - 59.5%) for the reference and non-coplanar techniques, respectively. The same trend was observed for heart exposure. CONCLUSIONS: The mixed technique showed a promising trend of reducing the volume of non-target breast tissue and heart exposure doses in APBI "complex cases". PMID- 22074548 TI - Frequency of Mouse Double Minute 2 (MDM2) and Mouse Double Minute 4 (MDM4) amplification in parosteal and conventional osteosarcoma subtypes. PMID- 22074549 TI - The benefit of the reverse transfer function in the fitting process of the Vibrant Soundbridge middle ear implant. AB - CONCLUSION: Reverse transfer function (RTF) measurement of the Vibrant Soundbridge (VSB) middle ear implant (MEI) is an objective method to evaluate the function of the VSB and can be used to adjust the Connexx value required to reach the optimal VSB gain during fitting sessions. OBJECTIVES: To investigate the sound transfer of the VSB with the RTF in implanted patients and evaluate the role of RTF in the fitting process of the VSB. METHODS: This was a prospective study including patients undergoing VSB implantation and RTF recording from March 2007 to October 2010. Three parameters were analyzed. 1) RTF: energy transmitted in dB SPL to ear canal by retrograde vibration of malleus and tympanic membrane. 2) Connexx value: level of amplification in dB delivered by the audioprocessor to the floating mass transducer (FMT). 3) VSB gain: difference in dB HL in free field between aided and unaided conditions. RESULTS: Ten patients fitted the criteria. RTF measurements revealed a significant inter-patient disparity. We adjusted the Connexx value according to the RTF value to obtain an optimal VSB gain within comfort levels. The VSB gain and RTF with Connexx value were closely correlated together. The mean VSB gain and RTF value converted to dB HL had comparable values. PMID- 22074550 TI - Selective targeted delivery of the TNF-alpha receptor p75 and uteroglobin to the vasculature of inflamed tissues: a preliminary report. AB - BACKGROUND: Ligand-targeted approaches have proven successful in improving the therapeutic index of a number of drugs. We hypothesized that the specific targeting of TNF-alpha antagonists to inflamed tissues could increase drug efficacy and reduce side effects. RESULTS: Using uteroglobin (UG), a potent anti inflammatory protein, as a scaffold, we prepared a bispecific tetravalent molecule consisting of the extracellular ligand-binding portion of the human TNF alpha receptor P75 (TNFRII) and the scFv L19. L19 binds to the ED-B containing fibronectin isoform (B-FN), which is expressed only during angiogenesis processes and during tissue remodeling. B-FN has also been demonstrated in the pannus in rheumatoid arthritis. L19-UG-TNFRII is a stable, soluble homodimeric protein that maintains the activities of both moieties: the immuno-reactivity of L19 and the capability of TNFRII to inhibit TNF-alpha. In vivo bio-distribution studies demonstrated that the molecule selectively accumulated on B-FN containing tissues, showing a very fast clearance from the blood but a very long residence time on B-FN containing tissues. Despite the very fast clearance from the blood, this fusion protein was able to significantly improve the severe symptomatology of arthritis in collagen antibody-induced arthritis (CAIA) mouse model. CONCLUSIONS: The recombinant protein described here, able to selectively deliver the TNF-alpha antagonist TNFRII to inflamed tissues, could yield important contributions for the therapy of degenerative inflammatory diseases. PMID- 22074551 TI - A multi-method evaluation of a training course on dual diagnosis. AB - A training course on dual diagnosis was developed within the Irish forensic mental health service, to bridge the gap in the lack of training on dual diagnosis in Ireland. The course was designed for service providers within mental health and addiction services. Twenty participants involving nursing, social work, police and social welfare disciplines attended the first training course. A mixed methodology research design was adapted to describe participants' evaluation of the training course. Data were collected using multiple methods: pre- and post-test, daily evaluation and focus group interviews. Quantitative data were analysed using the spss Version 16.0 and qualitative data were analysed thematically. Findings from the pre- and post-test suggest an increase in participants' knowledge of dual diagnosis and an increase in confidence in conducting groups. Daily evaluation indicates that the course content largely met participants' needs. Finally, three themes emerged from the focus group interview: increased confidence, the training course/teaching methods and personal/organizational challenges. This study implies that service providers within mental health and addiction services benefit from inter-professional, needs and skills based courses incorporating a variety of teaching methods. The way forward for future dual diagnosis training course developments would be working in partnership with service users and carers. PMID- 22074552 TI - Exon duplications in the ATP7A gene: frequency and transcriptional behaviour. AB - BACKGROUND: Menkes disease (MD) is an X-linked, fatal neurodegenerative disorder of copper metabolism, caused by mutations in the ATP7A gene. Thirty-three Menkes patients in whom no mutation had been detected with standard diagnostic tools were screened for exon duplications in the ATP7A gene. METHODS: The ATP7A gene was screened for exon duplications using multiplex ligation-dependent probe amplification (MLPA). The expression level of ATP7A was investigated by real-time PCR and detailed analysis of the ATP7A mRNA was performed by RT-PCR followed by sequencing. In order to investigate whether the identified duplicated fragments originated from a single or from two different X-chromosomes, polymorphic markers located in the duplicated fragments were analyzed. RESULTS: Partial ATP7A gene duplication was identified in 20 unrelated patients including one patient with Occipital Horn Syndrome (OHS). Duplications in the ATP7A gene are estimated from our material to be the disease causing mutation in 4% of the Menkes disease patients. The duplicated regions consist of between 2 and 15 exons. In at least one of the cases, the duplication was due to an intra-chromosomal event. Characterization of the ATP7A mRNA transcripts in 11 patients revealed that the duplications were organized in tandem, in a head to tail direction. The reading frame was disrupted in all 11 cases. Small amounts of wild-type transcript were found in all patients as a result of exon-skipping events occurring in the duplicated regions. In the OHS patient with a duplication of exon 3 and 4, the duplicated out-of-frame transcript coexists with an almost equally represented wild-type transcript, presumably leading to the milder phenotype. CONCLUSIONS: In general, patients with duplication of only 2 exons exhibit a milder phenotype as compared to patients with duplication of more than 2 exons. This study provides insight into exon duplications in the ATP7A gene. PMID- 22074554 TI - Fulminant myopericarditis in an immunocompetent adult due to pandemic 2009 (H1N1) influenza A virus infection. AB - Acute myopericarditis is a well-recognized but rare complication of numerous viral infections. Here we report a case of fulminant myopericarditis presenting with acute heart failure and a state of shock in a previously healthy young woman. H1N1 influenza A virus sequences were identified in throat and pericardial fluid, suggesting a viral source of the infection. PMID- 22074553 TI - Identification and analysis of phosphorylation status of proteins in dormant terminal buds of poplar. AB - BACKGROUND: Although there has been considerable progress made towards understanding the molecular mechanisms of bud dormancy, the roles of protein phosphorylation in the process of dormancy regulation in woody plants remain unclear. RESULTS: We used mass spectrometry combined with TiO2 phosphopeptide enrichment strategies to investigate the phosphoproteome of dormant terminal buds (DTBs) in poplar (Populus simonii * P. nigra). There were 161 unique phosphorylated sites in 161 phosphopeptides from 151 proteins; 141 proteins have orthologs in Arabidopsis, and 10 proteins are unique to poplar. Only 34 sites in proteins in poplar did not match well with the equivalent phosphorylation sites of their orthologs in Arabidopsis, indicating that regulatory mechanisms are well conserved between poplar and Arabidopsis. Further functional classifications showed that most of these phosphoproteins were involved in binding and catalytic activity. Extraction of the phosphorylation motif using Motif-X indicated that proline-directed kinases are a major kinase group involved in protein phosphorylation in dormant poplar tissues. CONCLUSIONS: This study provides evidence about the significance of protein phosphorylation during dormancy, and will be useful for similar studies on other woody plants. PMID- 22074555 TI - Interaction of G-quadruplexes with nonintercalating duplex-DNA minor groove binding ligands. AB - The enzyme telomerase synthesizes the G-rich DNA strands of the telomere and its activity is often associated with cancer. The telomerase may be therefore responsible for the ability of a cancer cell to escape apoptosis. The G-rich DNA sequences often adopt tetra-stranded structure, known as the G-quadruplex DNA (G4 DNA). The stabilization of the telomeric DNA into the G4-DNA structures by small molecules has been the focus of many researchers for the design and development of new anticancer agents. The compounds which stabilize the G-quadruplex in the telomere inhibit the telomerase activity. Besides telomeres, the G4-DNA forming sequences are present in the genomic regions of biological significance including the transcriptional regulatory and promoter regions of several oncogenes. Inducing a G-quadruplex structure within the G-rich promoter sequences is a potential way of achieving selective gene regulation. Several G-quadruplex stabilizing ligands are known. Minor groove binding ligands (MGBLs) interact with the double-helical DNA through the minor grooves sequence-specifically and interfere with several DNA associated processes. These MGBLs when suitably modified switch their preference sometimes from the duplex DNA to G4-DNA and stabilize the G4-DNA as well. Herein, we focus on the recent advances in understanding the G-quadruplex structures, particularly made by the human telomeric ends, and review the results of various investigations of the interaction of designed organic ligands with the G-quadruplex DNA while highlighting the importance of MGBL-G-quadruplex interactions. PMID- 22074556 TI - SLUG promotes prostate cancer cell migration and invasion via CXCR4/CXCL12 axis. AB - BACKGROUND: SLUG is a zinc-finger transcription factor of the Snail/Slug zinc finger family that plays a role in migration and invasion of tumor cells. Mechanisms by which SLUG promotes migration and invasion in prostate cancers remain elusive. METHODS: Expression level of CXCR4 and CXCL12 was examined by Western blot, RT-PCR, and qPCR analyses. Forced expression of SLUG was mediated by retroviruses, and SLUG and CXCL12 was downregulated by shRNAs-expressing lentiviruses. Migration and invasion of prostate cancer were measured by scratch wound assay and invasion assay, respectively. RESEARCH: We demonstrated that forced expression of SLUG elevated CXCR4 and CXCL12 expression in human prostate cancer cell lines PC3, DU145, 22RV1, and LNCaP; conversely, reduced expression of SLUG by shRNA downregulated CXCR4 and CXCL12 expression at RNA and protein levels in prostate cancer cells. Furthermore, ectopic expression of SLUG increased MMP9 expression and activity in PC3, 22RV1, and DU-145 cells, and SLUG knockdown by shRNA downregulated MMP9 expression. We showed that CXCL12 is required for SLUG mediated MMP9 expression in prostate cancer cells. Moreover, we found that migration and invasion of prostate cancer cells was increased by ectopic expression of SLUG and decreased by SLUG knockdown. Notably, knockdown of CXCL12 by shRNA impaired SLUG-mediated migration and invasion in prostate cancer cells. Lastly, our data suggest that CXCL12 and SLUG regulate migration and invasion of prostate cancer cells independent of cell growth. CONCLUSION: We provide the first compelling evidence that upregulation of autocrine CXCL12 is a major mechanism underlying SLUG-mediated migration and invasion of prostate cancer cells. Our findings suggest that CXCL12 is a therapeutic target for prostate cancer metastasis. PMID- 22074557 TI - Tracking plant, fungal, and bacterial DNA in honey specimens. AB - Consuming honey can result in adverse effects owing to poisoning by bacterial (botulism) or plant toxins. We have devised a method to extract polymerase chain reaction (PCR) amplifiable DNA of up to c. 400 bp in length based on dialysis of a 15-mL honey sample for 18 h against deionized water followed by sequential extraction using phenol, phenol/chloroform/isoamyl alcohol, chloroform/isoamyl alcohol, and ether. Sequence analysis of PCR products obtained using "universal" plant, fungal, and bacterial primers targeted to the ribosomal RNA genes has allowed us to identify six different orders of plants (Apiales, Fabales, Asterales, Solanales, Brassicales, and Sapindales), two orders of fungi (Entylomatales and Saccharomycetales), and six orders of bacteria (Sphingomonadales, Burkholderiales, Pseudomonadales, Enterobacteriales, Actinomycetales, and Bifidobacteriales) in a single honey specimen. PMID- 22074558 TI - Reactivity of amino acid nucleoside phosphoramidates: a mechanistic quantum chemical study. AB - Recent experimental evidence (Maiti et al. Chem.-Eur. J., submitted) indicates that hydrolysis of nucleoside phosphoramidates is subjected to anchimeric influence by carboxyl moieties in the leaving group but also by the base in the nucleotide. A quantum chemical analysis of these findings is presented. First the intrinsic hydrolysis mechanism is investigated for simplified model compounds, and then both amino acid and nucleoside substituents are included. It is found that hydrolysis is assisted by the alpha-carboxyl group via formation of a five membered intermediate and that the barrier for the reaction of this intermediate toward the product state can be influenced by the nucleobase. The adenine base protonated on N3 interacts with the transition state and considerably lowers the barrier for hydrolysis. The influence of several base modifications is explained by calculating the pK(a) for protonation on N3. PMID- 22074559 TI - Application of a C2-symmetric copper carbenoid in the enantioselective hydrosilylation of dialkyl and aryl-alkyl ketones. AB - We report excellent reactivity and enantioselectivity of a C(2)-symmetric copper bound N-heterocyclic carbene (NHC) in the hydrosilylation of a variety of structurally diverse ketones. This catalyst exhibits extraordinary enantioselctivity in the reduction of such challenging substrates as 2-butanone and 3-hexanone. Even at low catalyst loading (2.0 mol %), the reactions occur in under an hour at room temperature and often do not require purification beyond catalyst and solvent removal. The scope of this transformation was investigated in the reduction of 10 aryl-alkyl and alkyl-alkyl ketones. PMID- 22074560 TI - Efficacy of hydrosurgical debridement and nanocrystalline silver dressings for infection prevention in type II and III open injuries. AB - The aim of this study was to retrospectively evaluate the clinical and culture positive infection rates of open Gustilo/Anderson type II and III fractures using a protocol nanocrystalline silver wound dressing and hydrosurgical debridement. Retrospective case series through chart review on all type II and III open fractures were treated using a novel protocol from December 2005 to March 2008 (N = 17). All Gustilo/Anderson grade II and III open fractures were treated with a novel protocol at a Level I trauma centre. Open Gustilo/Anderson grade II and III fractures were acutely stabilised in the trauma centre/emergency department, while a nanocrystalline silver dressing was placed within the wound. Debridement using a hydrosurgical scalpel and gravity irrigation was performed within 6-8 hours of injury. Cultures were obtained prior to definitive fixation. The primary outcome measurements were positive cultures and clinical infection rates. Seventeen patients met inclusion criteria. Mean age (33.5) and injury severity score (12.7) were gathered. There were 4 grade II open fractures (23.5%), 11 grade IIIA (64.7%) and 2 grade IIIB open fractures (11.8%). The mean time to intravenous antibiotics was 61.5 minutes. The mean time to initial debridement/irrigation was 222.1 minutes. The average number of surgical procedures was 2.35 with a mean length of stay of 11.8 days. Six patients developed positive cultures from the traumatic wounds, five were contaminants. One clinical infection was found (methicillin-resistant Staphylococcus aureus). The overall clinical infection rate in this series was 5.9% (1/17). The only infection was in a Gustilo/Anderson grade II fracture. There were no infections in the more high-energy Gustilo/Anderson grade IIIA and IIIB fractures compared with the Gustilo/Anderson control of 4-42%. We conclude that this novel protocol for open-fracture treatment is a promising intervention. A further prospective randomised clinical study is warranted. PMID- 22074562 TI - Energy transfer in extended thienylene-phenylene-ethynylene dendrimers. AB - We present a new family of dendrimers with all-conjugated, thienylene (Th) containing photoactive backbones and branched end-groups. Steady-state spectroscopy demonstrates a donor-acceptor system, while picosecond time-resolved fluorescence characterizes a vectorial energy transfer from phenylene-ethynylene (PE) units at the periphery to thienylene-containing PE units at the core. Energy transfer rates of 1.5 and 3.5 ps are observed for generation 2 and 3 dendrimers, indicative of a weakly coupled donor-acceptor system, with couplings on the order of 40-60 cm(-1). PMID- 22074561 TI - Design and synthesis of novel 2-(3-substituted propyl)-3-(2-methyl phenyl) quinazolin-4-(3H)-ones as a new class of H1-antihistaminic agents. AB - A series of novel 2-(3-substituted propyl)-3-(2-methyl phenyl) quinazolin-4-(3H) ones were synthesized by the reaction of 2-(3-bromopropyl thio)-3-(2-methyl phenyl) quinazolin-4-(3H)-one with various amines. The starting material, 2-(3 bromopropyl thio)-3-(2-methyl phenyl) quinazolin-4-(3H)-one was synthesized from 2-methyl aniline. When tested for their in vivo H(1)-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly. Compound 2-(3-(4-methylpiperazin-1 yl) propylthio)-3-(2-methyl phenyl) quinazolin-4(3H)-one (OT5) emerged as the most active compound (71.70% protection) of the series when compared to the reference standard chlorpheniramine maleate (70.09% protection). Compound OT5 shows negligible sedation (7%) compared to chlorpheniramine maleate (33%). Therefore, compound OT5 can serve as the leading molecule for further development into a new class of H(1)-antihistaminic agents. PMID- 22074563 TI - 5-HT(3) and 5-HT(4) receptors contribute to the anti-motility effects of Garcinia buchananii bark extract in the guinea-pig distal colon. AB - BACKGROUND: Garcinia buchananii bark extract is an anti-motility diarrhea remedy. We investigated whether G. buchananii bark extract has components that reduce gastrointestinal peristaltic activity via 5-HT(3) and 5-HT(4) receptors. METHODS: Aqueous G. buchananii extract was separated into fractions using preparative thin layer chromatography (PTLC), and major chemical components were identified using standard tests. The anti-motility effects of the extract and its fractions (PTLC1 5) were studied through pellet propulsion assays using isolated guinea-pig distal colons. KEY RESULTS: Anti-motility (PTLC1 & PTLC5) and pro-motility (PTLC2) fractions were isolated from the extract. Flavonoids, steroids, alkaloids, tannins, and phenols were identified in the extract and PTLC1&5. The potency of the extract applied via the mucosal surface was reduced by 5-HT, 5-HT(3) receptor agonist RS-56812, 5-HT(4) receptor agonists cisapride and CJ-033466, 5-HT(3) receptor antagonist granisetron, and 5-HT(4) receptor antagonist GR-113808. The anti-motility effects of the aqueous extract and PTLC1&5 when applied serosally were reversed by RS-56812, cisapride, and CJ-033466. The 5-HT(3) receptor antagonists, granisetron and ondansetron, reduced the effects of the extract to an extent and completely reversed the anti-motility effects of PTLC1&5. GR-113808 inhibited the actions of the extract during the initial 10 min, but enhanced the extracts' anti-motility effects after 15 min. GR-113808 augmented the anti motility activities of PTLC1 and PTLC5 by 30%. CONCLUSIONS & INFERENCES: These results indicate that the anti-motility effects of G. buchananii aqueous extract are potentially mediated by compounds that affect 5-HT(3) and 5-HT(4) receptors. Identification and characterization of the bioactive compounds within G. buchananii could lead to the discovery of new non-opiate anti-diarrhea formulations. PMID- 22074564 TI - Configuring health care for systematic behavioral screening and intervention. AB - The United States Preventive Services Task Force recommends universal screening and intervention for tobacco use, excessive drinking, and depression. These services improve health outcomes, decrease health care costs, enhance public safety, and generate substantial return on investment. Given the prevalence rates of these behavioral conditions and the time necessary for evidence-based interventions, it will be challenging to integrate behavioral screening and intervention (BSI) into busy health care settings. Therefore, consistent with the principles of the medical home and the chronic care model, the health care team must be expanded to systematically provide BSI. A 2-tiered, stepped-care model is proposed. The first tier of services-consisting of assessment, intervention, and follow-up services-would address most mild-to-moderate behavioral risks or conditions. The second tier would include various specialty-based resources, which would be conserved for patients with greatest need and potential to benefit. With slight enhancement of their training, health educators would be excellent candidates to serve as cost-efficient providers of first-tier services. The proposed model would help the United States realize improved health outcomes and cost savings as health care benefits are expanded to a greater proportion of its population. PMID- 22074565 TI - Challenge of neurological and psychosocial problems in developing countries. PMID- 22074566 TI - European veterinary dissertations. PMID- 22074567 TI - Association of the 5-HT2A receptor gene polymorphisms with obstructive sleep apnea hypopnea syndrome in Chinese Han population. AB - CONCLUSIONS: The -1438G/A polymorphism of 5-HT2A receptor gene may associate with obstructive sleep apnea hypopnea syndrome (OSAHS) in a Chinese Han population. Different genotypes of -1438G/A polymorphism may influence the ventilatory activity in response to hypoxia, and in turn the sleep breath status. OBJECTIVE: This study was designed to assess the association of polymorphisms in all exons and promoter region of the 5-HT2A receptor gene with OSAHS in a Chinese Han population. METHODS: A total of 315 subjects (210 patients and 105 controls) were included for genetic analyses of polymorphisms in all exons and promoter region of the 5-HT2A receptor gene. RESULTS: Six single nucleoside polymorphism (SNP) sites were identified in the sequencing of the promoter and exons of the 5-HT2A receptor gene; however, genotypes and allele frequencies of the SNPs did not show significant differences between the patients and controls except the -1438G/A polymorphism. For SNP of -1438G/A, the A/A genotype was over-represented and the allele A was more frequent in the patients, while the G/A genotype was over represented and the allele G was more frequent in the controls (p < 0.001, p = 0.005, respectively). In the patients, the A/A and G/A genotypes were over represented in the subgroups with lowest nocturnal SaO(2) (LSaO(2)) <=75% and LSaO(2) >75%, respectively (p = 0.006). PMID- 22074568 TI - A bacteria colony-based screen for optimal linker combinations in genetically encoded biosensors. AB - BACKGROUND: Fluorescent protein (FP)-based biosensors based on the principle of intramolecular Forster resonance energy transfer (FRET) enable the visualization of a variety of biochemical events in living cells. The construction of these biosensors requires the genetic insertion of a judiciously chosen molecular recognition element between two distinct hues of FP. When the molecular recognition element interacts with the analyte of interest and undergoes a conformational change, the ratiometric emission of the construct is altered due to a change in the FRET efficiency. The sensitivity of such biosensors is proportional to the change in ratiometric emission, and so there is a pressing need for methods to maximize the ratiometric change of existing biosensor constructs in order to increase the breadth of their utility. RESULTS: To accelerate the development and optimization of improved FRET-based biosensors, we have developed a method for function-based high-throughput screening of biosensor variants in colonies of Escherichia coli. We have demonstrated this technology by undertaking the optimization of a biosensor for detection of methylation of lysine 27 of histone H3 (H3K27). This effort involved the construction and screening of 3 distinct libraries: a domain library that included several engineered binding domains isolated by phage-display; a lower-resolution linker library; and a higher-resolution linker library. CONCLUSION: Application of this library screening methodology led to the identification of an optimized H3K27 trimethylation biosensor that exhibited an emission ratio change (66%) that was 2.3 * improved relative to that of the initially constructed biosensor (29%). PMID- 22074570 TI - Evaluation of compressive strength in the first premolars between young and elderly people: ex vivo study. AB - OBJECTIVE: This study evaluated the compressive strength of first maxillary premolars from young and elderly people. BACKGROUND: Findings have revealed that changes happening on dental structure lead to a higher susceptibility of tooth fracture. MATERIALS AND METHODS: Thirty teeth were divided into four groups as follows: G I (n = 7) premolars of elderly patients with fused roots, G II (n = 8) premolars of elderly with separate roots, G III (n = 7) pre-molars of young people with fused roots and G IV (n = 8) premolars of young people with roots separated. The roots were placed in polyvinyl chloride (PVC) cylinder and embedded in acrylic resin. Afterward, the samples were subjected to fracture by compressive strength in a universal testing machine. Loads were applied in continuous and progressive speed of 0.5 mm/min until the moment of fracture. The values found underwent statistical analysis (ANOVA alpha = 0.05). RESULTS: With regard to age, there was a statistical difference, the teeth of the elderly being more susceptible to fracture (p < 0.05). With regard to root morphology, no significant differences between both groups were observed (p > 0.05). CONCLUSION: It was concluded that with the methodology employed, the age factor was important with regard to fracture resistance to compression. PMID- 22074569 TI - Genome-scale reconstruction and system level investigation of the metabolic network of Methylobacterium extorquens AM1. AB - BACKGROUND: Methylotrophic microorganisms are playing a key role in biogeochemical processes - especially the global carbon cycle - and have gained interest for biotechnological purposes. Significant progress was made in the recent years in the biochemistry, genetics, genomics, and physiology of methylotrophic bacteria, showing that methylotrophy is much more widespread and versatile than initially assumed. Despite such progress, system-level description of the methylotrophic metabolism is currently lacking, and much remains to understand regarding the network-scale organization and properties of methylotrophy, and how the methylotrophic capacity emerges from this organization, especially in facultative organisms. RESULTS: In this work, we report on the integrated, system-level investigation of the metabolic network of the facultative methylotroph Methylobacterium extorquens AM1, a valuable model of methylotrophic bacteria. The genome-scale metabolic network of the bacterium was reconstructed and contains 1139 reactions and 977 metabolites. The sub-network operating upon methylotrophic growth was identified from both in silico and experimental investigations, and 13C-fluxomics was applied to measure the distribution of metabolic fluxes under such conditions. The core metabolism has a highly unusual topology, in which the unique enzymes that catalyse the key steps of C1 assimilation are tightly connected by several, large metabolic cycles (serine cycle, ethylmalonyl-CoA pathway, TCA cycle, anaplerotic processes). The entire set of reactions must operate as a unique process to achieve C1 assimilation, but was shown to be structurally fragile based on network analysis. This observation suggests that in nature a strong pressure of selection must exist to maintain the methylotrophic capability. Nevertheless, substantial substrate cycling could be measured within C2/C3/C4 inter-conversions, indicating that the metabolic network is highly versatile around a flexible backbone of central reactions that allows rapid switching to multi-carbon sources. CONCLUSIONS: This work emphasizes that the metabolism of M. extorquens AM1 is adapted to its lifestyle not only in terms of enzymatic equipment, but also in terms of network-level structure and regulation. It suggests that the metabolism of the bacterium has evolved both structurally and functionally to an efficient but transitory utilization of methanol. Besides, this work provides a basis for metabolic engineering to convert methanol into value-added products. PMID- 22074571 TI - Ten-year experiences with Tracheostomy at a University teaching hospital in Northwestern Tanzania: A retrospective review of 214 cases. AB - BACKGROUND: Tracheostomy remains a very important life saving surgical procedure worldwide and particularly in our environment where patients present late in upper airway obstruction. Little work has been done on this subject in our environment and therefore it was necessary to conduct this study to describe our own experiences with tracheostomy, outlining the common indications and outcome of tracheostomized patients in our setting and compare our results with those from other centers in the world. METHODS: This was a 10-year retrospective study which was conducted at Bugando Medical Centre from January 2001 to December 2010. Data were retrieved from patients' files kept in the Medical record department and analyzed using SPSS computer software version 15.0. Ethical approval to conduct the study was obtained from relevant authority before the commencement of the study. RESULTS: A total of 214 patients were studied. The male to female ratio was 3.1: 1. The majority of patients were in the 3rd decade of life. The most common indication for tracheostomy was upper airway obstruction secondary to traumatic causes in 55.1% of patients, followed by upper airway obstruction due to neoplastic causes in 39.3% of cases. The majority of tracheostomies (80.4%) were performed as an emergency. Transverse skin crease incision was employed in all the cases. Post-tracheostomy complication rate was 21.5%. Complication rate was significantly higher in emergency tracheostomy than in electives (P < 0.001). The duration of temporary tracheostomy ranged from 8 days to 46 months, with a median duration of 4 months. Tracheostomy decannulation was successively performed in 72.4% of patients who survived. Mortality rate was 13.6%. The mortality was due to their underlying illnesses, none had tracheostomy-related mortality. CONCLUSION: Upper airway obstruction secondary to trauma and laryngeal tumors still remains the most common indication for tracheostomy in our centre and tracheostomy is still a life saving procedure in the surgical management of airway despite complications which are seen more commonly in paediatric patients. Most of tracheostomy related complications can be avoided by meticulous attention to the details of the technique and postoperative tracheostomy care by skilled and trained staff. PMID- 22074572 TI - Ghrelin, a novel peptide hormone in the regulation of energy balance and cardiovascular function. AB - Ghrelin, a peptide hormone predominantly produced by the stomach, is a potent stimulator of growth hormone release, food intake and weight gain. Besides its functions in regulating energy homeostasis, ghrelin has pronounced cardioprotective effects and was shown to improve cardiac performance in chronic heart failure (CHF). The multifunctional nature of ghrelin makes it an interesting pharmacological target for various diseases. Inhibition of ghrelin could be a promising approach in obesity-related disorders, while an enhancement of the ghrelin response is considered beneficial in several pathologic conditions marked by malnutrition, wasting and cachexia, including CHF, cancer, chronic pulmonary disease or chronic infections. In particular, patients suffering from CHF could possibly benefit from ghrelin based compounds that do not only help to reverse cardiac cachexia - by inducing a positive energy balance - but also enhance the direct cardioprotective effects of ghrelin. This review highlights the role of ghrelin in the regulation of energy balance and cardiovascular function and summarizes the most recent patents, developments and strategies in ghrelin-based pharmacotherapy for the treatment of pathologic conditions associated with obesity, cachexia or cardiovascular dysfunction. PMID- 22074573 TI - The monocyte locomotion inhibitory factor an anti-inflammatory peptide; therapeutics originating from amebic abscess of the liver. AB - Entamoeba histolytica in culture produces a pentapeptide (MQCNS). This oligopeptide inhibits the in vitro and in vivo locomotion of human monocytes, hence its denomination Monocyte Locomotion Inhibitory Factor (MLIF). The original isolated peptide and its synthetic construct display similar effects, among others, being inhibition of the respiratory burst in monocytes and neutrophils, decrease of Dinitrochlorobenzene (DNCB) skin hypersensitivity in guinea pigs and gerbils, and delay of mononuclear leukocytes in human Rebuck skin windows with inhibition of vascular cell Very late antigen (VLA)-4 and Vascular adhesion molecules (VCAM) in endothelia and monocytes. The MLIF molecular mechanism of action is unknown, but data reveal its implication in Nuclear factor-kappa B (NF kappaB) and Mitogenactivated protein kinase (MAPK) pathways. This could explain MLIF multiplicity of biological effects. On the other hand, the amebic peptide has been useful in treating experimental amebiasis of the liver. The amebic peptide is effective in reducing inflammation induced by carragenin and arthritis in a Collagen-induced arthritis (CIA) model. Microarray data from experimental arthritis revealed an MLIF gene expression profile that includes genes that are involved in apoptosis, cell adhesion, extracellular matrix, and inflammation / chemotaxis. MLIF could be involved in unsuspected biological factions because there is increasing data on the peptide effect on several cell activities. This review also presents uses of MLIF as described in patents. PMID- 22074575 TI - GLUT4 associated proteins as therapeutic targets for diabetes. AB - Type 2 diabetes is a complex, multifactorial disease resulting from insulin resistance in target tissues and the impairment of insulin secretion from the pancreas. One of the key metabolic actions of insulin is to control blood sugar levels by promoting glucose uptake into adipocyte and muscle cells. This is achieved by activation of a complex signal transduction cascade that stimulates the trafficking of the insulin responsive glucose transporter protein, GLUT4, from specific intracellular sites to the plasma membrane. This review is divided into two major sections. The first section gives an overview of GLUT4 trafficking and the second section focuses on the patents that have been acquired for GLUT4 associated proteins and which demonstrate potential as therapeutic targets for the treatment of diabetes. Inventions in this area include methods and agents to translocate GLUT4 to the plasma membrane independent of insulin and methods to increase the level of GLUT4 in insulin responsive cells. PMID- 22074574 TI - Pharmacoperones: a new therapeutic approach for diseases caused by misfolded G protein-coupled receptors. AB - G Protein-coupled receptors (GPCRs) are cell membrane proteins that recognize specific chemical signals such as drugs and hormones and transduce these signals into cellular responses by activating G-proteins. As is the case for all newly synthesized proteins, GPCRs are subjected to conformational scrutiny at the endoplasmic reticulum prior to processing and trafficking to the cell surface membrane. Because of this stringent quality control screening mechanism, mutations that result in protein misfolding frequently lead to retention in the endoplasmic reticulum, aggregation or other misrouting and, eventually, to disease. This article reviews some patents and new therapeutic opportunities based on the misfolding and retention of otherwise functional GPCRs that represent promising approaches to correct conformational abnormalities leading to distinct disease states. PMID- 22074576 TI - Exploring the Role of "Brahmi" (Bacopa monnieri and Centella asiatica) in Brain Function and Therapy AB - It has been envisaged that in this century, disorders of the central nervous system will have a significant bearing on the healthcare concerns of the human population worldwide. Such neurological and psychiatric disorders are generally associated with loss of memory, cognitive deficits, impaired mental function etc. Due to the multi-factorial nature of these diseases, modern medicine based psychoactive drugs have met with limited success. Therefore, there is a growing demand for novel products that could target multiple pathways and improve the mental capabilities either independently or in combination with conventional drugs. In the recent times, herbal products based on traditional knowledge have been increasingly used both in developed and developing countries. According to "Ayurveda", the Indian traditional system of medicine, "medhyarasayanas" represent herbal therapeutics that boost memory, restore cognitive deficits and improve mental function. The current review deals with the components and application of such a traditional herb "Brahmi" that corresponds to two plants, Bacopa monnieri and Centella asiatica. Research evidences clearly indicate that both plants possess neuroprotective properties, have nootropic activity with therapeutic implications for patients with memory loss. The field has witnessed exciting patent activity with most inventions aiming at either (i) improving the methods of herbal extraction or (ii) enrichment and purification of novel compounds from brahmi or (iii) providing novel synergistic formulations for therapeutics in various human ailments. In this review, clinical trials related to the therapeutic properties of brahmi and current patents relevant to the preparation, composition and application have also been included. PMID- 22074577 TI - The alteration of coagulation in patients with thyroid dysfunction. AB - The influence of thyroid dysfunction on haemostasis is complex and still not very well understood. Both bleeding tendency and hypercoagulable states have been reported. In this article, we attempt to discuss the possible relationship between thyroid dysfunction and secondary haemostasis and fibrinolysis. After the analysis of the recent literature, we conclude that thyroid dysfunction is associated with alterations in fibrin generation and fibrinolysis. Most of the evidence suggests that hyperthyroidism is associated with impaired fibrinolysis and enhanced coagulation. Although, former studies proposed that there was an increase in fibrinolytic activity in hypothyroidism, increasing number of recent reports advocated the opposite. We believe that further prospective comprehensive clinical studies involving large numbers of patients either with overt or subclinical thyroid dysfunctions should be performed to clarify the effect of thyroid dysfunction on secondary haemostasis and fibrinolysis. Recent important patents focusing on coagulation and thyroid dysfunction are also discussed in this review. PMID- 22074578 TI - Pituitary microadenoma treated with antipsychotic drug aripiprazole. AB - Male patient 24 years old with a pituitary microadenoma and mental and behavioural disorders due to multiple drug use and use of other psychoactive substances (cocaine, cannabis and alcohol) were treated with haloperidol (dopamine receptor blocker) 10 mg daily. In the last control, the patient presented mammary hypertrophy; laboratory testing and brain magnetic resonance imaging (MRI) was performed, reporting the presence of a pituitary microadenoma syndrome with hormonal alteration (Prolactin levels 28.4 ng/ml). Haloperidol, carbamazepine and levomepromazine were then discontinued. He was started on aripiprazole 15 mg po daily for 4 days; the dosage was then increased to 30 mg po daily, with Valproic Acid 500 mg po tid. After 3 weeks on aripiprazole, the mammary hypertrophy that had increased in the patient had resolved. After 10 weeks follow up of prolactin revealed a normal level, at 4.33 ng/ml. Insomnia, aggressiveness, irritability, visual, tactile and auditory hallucinations remained absent after treatment with aripiprazole which is not a first line drug in multiple drug use patient with psychosis. We also consider the correlation of drug use in patient with psychosis, haloperidol treatment, pituitary microadenoma syndrome, hyperprolactinemia, and dopamine D2- receptor partial agonist aripiprazole treatment. This article also summarizes some relevant patents. PMID- 22074579 TI - Dopamine: the forgotten felon in type 2 diabetes. AB - This paper reviews recent patents and development related to bromocriptine and other dopaminergic agents, being used or suggested for use in the management of diabetes. The article discusses the contribution of dopaminergic pathways to glucose, energy and weight homeostasis. The mechanism of action of bromocriptine, its pharmacological properties, efficacy, safety and tolerability are assessed. The article also covers recent patents which may be utilized to improve the efficiency and tolerability of dopamine-based therapy in diabetes mellitus. PMID- 22074580 TI - Hypoglycemic agents in the management of type 2 diabetes mellitus. AB - Type 2 diabetes is increasing in prevalence and causes a significant health care burden due to associated microvascular and macrovascular complications. Type 2 diabetes is diagnosed by clinical findings of hyperglycemia and laboratory confirmation of elevated plasma glucose. Initial therapy includes diet and exercise, followed by the use of oral hypoglycemic agents and potentially subcutaneous insulin injections. Of the oral hypoglycemic agents currently available, metformin is the first-line choice. Recently, new adjunct therapies have been introduced that can improve glycemic control, although the long term effects on modifying the disease outcome in terms of diabetes complications remain to be seen. A review of the mechanism of action of current, non-insulin therapies will be presented. This review article will also discuss recent patents related to the field. PMID- 22074582 TI - The pineal hormone melatonin in health and disease. PMID- 22074583 TI - The use of chronobiotics in the resynchronization of the sleep/wake cycle. Therapeutical application in the early phases of Alzheimer's disease. AB - Treatment of circadian rhythm disorders, whether precipitated by intrinsic factors (e.g., sleep disorders, blindness, mental disorders, aging) or by extrinsic factors (e.g., shift work, jet-lag) has led to the development of a new type of agents called "chronobiotics". The term "chronobiotic" defines a substance displaying the therapeutic activity of shifting the phase or increasing the amplitude of the circadian rhythms. The prototype of this therapeutic group is melatonin, whose administration synchronizes the sleep-wake cycle in blind people and in individuals suffering from circadian rhythm sleep disorders, like delayed sleep phase syndrome, jet lag or shift-work. Daily melatonin production decreases with age, and in several pathologies, attaining its lowest values in Alzheimer's disease (AD) patients. About half of dementia patients have severe disruptions in their sleep-wakefulness cycle. Melatonin replacement is effective to treat sundowning and other sleep wake disorders in fully developed AD, although controversial data on this point exist. Indeed, large interindividual differences between patients suffering from AD exist and can explain these erratic results. Theoretically the effect of melatonin could be more consistent at an earlier stage of the disease, i.e., mild cognitive impairment (MCI), an etiologically heterogeneous syndrome that precedes dementia. PubMed was searched using Entrez for articles including clinical trials. Search terms were "Alzheimer" "mild cognitive impairment" and "melatonin". Full publications were obtained and references were checked for additional material where appropriate. Only clinical studies with empirical treatment data were reviewed. Five double blind, randomized placebo-controlled trials and 1 open-label retrospective study (N = 651) all agree in indicating that treatment with daily evening melatonin improves sleep quality and cognitive performance in MCI. The analysis of published evidence and patents indicates that melatonin can be a useful ad-on therapeutic tool in the early phases of AD. PMID- 22074584 TI - Relevance of the chronobiological and non-chronobiological actions of melatonin for enhancing therapeutic efficacy in neurodegenerative disorders. AB - Melatonin is an indolamine with a large spectrum of functions that can be divided into chronobiotic and nonchronobiotic. Chronobiotic effects are mediated by the daily rhythm of melatonin in the plasma due to nocturnal pineal synthesis, whereas the melatonin produced by other cells, such as gastrointestinal and immune competent cells, is independent of the light/dark cycle and exert non chronobiotic effects. The concentrations achieved by the two sources are significantly different, varying in the pM-nM range in the plasma, and may achieve concentrations in the mM range when released locally by activated immune competent cells. Consequently, the effects of the melatonin produced in these two situations are distinct. Much has been reported about the beneficial response to exogenous melatonin administration in several pathological conditions. However, the relationship between the establishment of a disease and the state of the physiological activity of the pineal gland is still poorly understood. Here, we review the state of art in the modulation of pineal melatonin synthesis, relevant patents, and discuss its relationship with neurodegenerative disorders that involve a central inflammatory response, such as Alzheimer's disease, to suggest the putative relevance of new therapeutic protocols that replace this pineal hormone. PMID- 22074585 TI - Effects of melatonin on peripheral nerve regeneration. AB - In the available literature, there are thousands of studies on peripheral nerve regeneration using many nerves of several animals at different ages with various types of lesions and different methods of evaluation at certain time of follow up. Despite many experimental data and clinical observations, there is still no ideal treatment method enhancing peripheral nerve regeneration. In clinical practice, various types of surgical nerve repair techniques do not frequently result in complete recovery due to neuroma formation, lipid peroxidative damage, ischemia and other factors. Recently, a number of neuroscientists demonstrated that pineal neurohormone melatonin (MLT) has an effect on the morphologic features of the nerve tissue, suggesting its neuroprotective, free radical scavenging, antioxidative, and analgesic effects in degenerative diseases of peripheral nerves. At present, it is widely accepted that MLT has a useful effect on axon length and sprouting after traumatic events to peripheral nerves. Our studies using various experimental injury models clearly suggest positive effects of MLT on the number of axons, thickness of myelin sheath by inhibition of collagen accumulation and neuroma formation following traumatic events to peripheral nerves, myelination of developing peripheral nerve after intrauterine ethanol exposure. Nevertheless, further experimental and randomized controlled clinical studies are vital to identify the clinical use of MLT hormone. This is an overview of recent patents and current literature in terms of the effects of MLT on peripheral nerve regeneration based on a critical analysis of electrophysiological, biochemical and light and electron microscopic findings, in addition to functional observations. PMID- 22074586 TI - Melatonin, immune function and cancer. AB - Melatonin is a natural substance ubiquitous in distribution and present in almost all species ranging from unicellular organisms to humans. In mammals, melatonin is synthesized not only in the pineal gland but also in many other parts of the body, including the eyes, bone marrow, gastrointestinal tract, skin and lymphocytes. Melatonin influences almost every cell and can be traced in membrane, cytoplasmic, mitochondrial and nuclear compartments of the cell. The decline in the production of melatonin with age has been suggested as one of the major contributors to immunosenescence and development of neoplastic diseases. Melatonin is a natural antioxidant with immunoenhancing properties. T-helper cells play an important role for protection against malignancy and melatonin has been shown to enhance T-helper cell response by releasing interleukin-2, interleukin-10 and interferon-gamma. Melatonin is effective in suppressing neoplastic growth in a variety of tumors like melanoma, breast and prostate cancer, and ovarian and colorectal cancer. As an adjuvant therapy, melatonin can be beneficial in treating patients suffering from breast cancer, hepatocellular carcinoma or melanoma. In this paper, a brief review of recent patents on melatonin and cancer has also been presented. PMID- 22074587 TI - Fetuin-A: a multifunctional protein. AB - Sixty-six years have elapsed since the discovery of fetuin in 1944, but its importance in mammalian physiology has only recently been appreciated. Fetuin, first isolated from fetal bovine serum and now most commonly known as either fetuin-A, alpha-2-HS-glycoprotein (recommended name by UniprotKB and PIR), or alpha2-Heremans-Schmid glycoprotein, functions as an important component of diverse normal and pathological processes, including vascular calcification and bone metabolism regulation, insulin resistance, protease activity control, keratinocytes migration, and breast tumor cell proliferative signaling. Fetuin-A has also been identified as a biomarker for neurodegenerative disease. Here, we summarize recent publications focusing on the structural and functional properties of fetuin-A. The emerging importance of fetuin-A for both diagnosis and therapeutics has come to the attention of the pharmaceutical industry. Therefore, we will discuss the status of patents based on fetuin-A. PMID- 22074588 TI - Better targeting melanoma: options beyond surgery and conventional chemotherapy. AB - Skin cancer is the commonest malignant tumour in white skinned individuals in the western world. The incidence of skin cancer is on the rise. Case fatality for melanoma is probably the highest, not only among skin cancers but also among all types of cancers. The notion that cancer stem cells are responsible for disease progress and development has lead researchers towards these initiators of new metastases. Intra- and extracellular path inhibitors are targeted in eliminating crucial functions of tumor cells. Treatments are easily escaped from stem cells with pluripotent functional and proliferative potential. Immunomodulators are a useful treatment adjunct for highly immunogenic cancers such as malignant melanoma. Specific lineages of tumor cells are responsible for this modulation and targeting this cancer function with specific antibodies appears to be a reasonable but also effective treatment option. Chemoprotective agents have been proposed as a mean of reducing dose dependent toxicities and enlarging the therapeutic window of anticancer drugs. Current patent laws skew biomedical research to products that yield high profits rather than to global priority health needs in both developed and developing countries and with melanoma benefiting from this skew many new patents will continue to emerge. Most patents reported in this review follow the cytostatic rather than the cytotoxic paradigm. Based on this trend, one might anticipate that the goal for future advances in the treatment of melanoma patients would be to prolong their lifespan rather than cure them. PMID- 22074590 TI - Staff concerns in heroin-assisted treatment centres. AB - Heroin-assisted treatment (HAT) is a solution for improving the condition of treatment-resistant heroin addicts. Since 1994, six randomized controlled trials have concluded that HAT is more efficacious than oral methadone for severe heroin addicts. We visited seven HAT treatment centres in four countries in order to observe diacetylmorphine (DAM) administration and to study the main concerns of the staff. Nurses were concerned by the risk taken if a previously intoxicated patient received his dose of DAM. Another concern was the smuggling of DAM doses. The HAT centres face a dilemma: treating patients while at the same time allowing their risky street habits in the centre. PMID- 22074589 TI - Residual HIV-1 DNA Flap-independent nuclear import of cPPT/CTS double mutant viruses does not support spreading infection. AB - BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) central DNA Flap is generated during reverse transcription as a result of (+) strand initiation at the central polypurine tract (cPPT) and termination after a ca. 100 bp strand displacement at the central termination sequence (CTS). The central DNA Flap is a determinant of HIV-1 nuclear import, however, neither cPPT nor CTS mutations entirely abolish nuclear import and infection. Therefore, to determine whether or not the DNA Flap is essential for HIV-1 nuclear import, we generated double mutant (DM) viruses, combining cPPT and CTS mutations to abolish DNA Flap formation. RESULTS: The combination of cPPT and CTS mutations reduced the proportion of viruses forming the central DNA Flap at the end of reverse transcription and further decreased virus infectivity in one-cycle titration assays. The most affected DM viruses were unable to establish a spreading infection in the highly permissive MT4 cell line, nor in human primary peripheral blood mononuclear cells (PBMCs), indicating that the DNA Flap is required for virus replication. Surprisingly, we found that DM viruses still maintained residual nuclear import levels, amounting to 5-15% of wild-type virus, as assessed by viral DNA circle quantification. Alu-PCR quantification of integrated viral genome also indicated 5-10% residual integration levels compared to wild type virus. CONCLUSION: This work establishes that the central DNA Flap is required for HIV-1 spreading infection but points to a residual DNA Flap independent nuclear import, whose functional significance remains unclear since it is not sufficient to support viral replication. PMID- 22074592 TI - Effectiveness and tissue compatibility of a 12-week treatment of chronic venous leg ulcers with an octenidine based antiseptic--a randomized, double-blind controlled study. AB - The aim of this study was to evaluate the cytotoxic effect of octenidine dihydrochloride/phenoxyethanol (OHP) found in vitro by conducting a randomized, double-blind controlled clinical study focusing on its safe and effective use in chronic venous leg ulcers. In total, 126 male and female patients were treated with either OHP (n = 60) or Ringer solution (n = 66). The treatment lasted over a period of maximum 12 weeks. For the assessment of the wound-healing process, clinical outcome parameters were employed, that is, time span until 100% epithelization, wound status and the wound surface area were analysed. Side effects were recorded during the study period. The median time to complete ulcer healing was comparable between the OHP and Ringer solution groups (92 versus 87 days; P = 0.952), without being influenced by wound size or duration of the target ulcer (P-values: 0.947/0.978). In patients treated with OHP, fewer adverse events (AEs) were observed compared with the Ringer group (17% versus 29% of patients reported 20 versus 38 AEs). OHP is well suitable for the treatment of chronic wounds without cytotoxic effects. Furthermore, OHP does not impair the wound healing in chronic venous ulcers. PMID- 22074591 TI - Results from the translation and adaptation of the Iranian Short-Form McGill Pain Questionnaire (I-SF-MPQ): preliminary evidence of its reliability, construct validity and sensitivity in an Iranian pain population. AB - BACKGROUND: The Short Form McGill Pain Questionnaire (SF-MPQ) is one of the most widely used instruments to assess pain. The aim of this study was to translate and culturally adapt the questionnaire for Farsi (the official language of Iran) speakers in order to test its reliability and sensitivity. METHODS: We followed Guillemin's guidelines for cross-cultural adaption of health-related measures, which include forward-backward translations, expert committee meetings, and face validity testing in a pilot group. Subsequently, the questionnaire was administered to a sample of 100 diverse chronic pain patients attending a tertiary pain and rehabilitation clinic. In order to evaluate test-retest reliability, patients completed the questionnaire in the morning and early evening of their first visit. Finally, patients were asked to complete the questionnaire for the third time after completing a standardized treatment protocol three weeks later. Intraclass correlation coefficient (ICC) was used to evaluate reliability. We used principle component analysis to assess construct validity. RESULTS: Ninety-two subjects completed the questionnaire both in the morning and in the evening of the first visit (test-retest reliability), and after three weeks (sensitivity to change). Eight patients who did not finish treatment protocol were excluded from the study. Internal consistency was found by Cronbach's alpha to be 0.951, 0.832 and 0.840 for sensory, affective and total scores respectively. ICC resulted in 0.906 for sensory, 0.712 for affective and 0.912 for total pain score. Item to subscale score correlations supported the convergent validity of each item to its hypothesized subscale. Correlations were observed to range from r2 = 0.202 to r2 = 0.739. Sensitivity or responsiveness was evaluated by pair t-test, which exhibited a significant difference between pre- and post-treatment scores (p < 0.001). CONCLUSION: The results of this study indicate that the Iranian version of the SF-MPQ is a reliable questionnaire and responsive to changes in the subscale and total pain scores in Persian chronic pain patients over time. PMID- 22074593 TI - The jump shot - a biomechanical analysis focused on lateral ankle ligaments. AB - Handball is one of the top four athletic games with highest injury risks. The jump shot is the most accomplished goal shot technique and the lower extremities are mostly injured. As a basis for ankle sprain simulation, the aim of this study was to extend the ankle region of an existing musculoskeletal full-body model through incorporation of three prominent lateral ankle ligaments: ligamentum fibulotalare anterius (LFTA), ligamentum fibulotalare posterius (LFTP), ligamentum fibulocalcaneare (LFC). The specific objective was to calculate and visualise ligament force scenarios during the jumping and landing phases of controlled jump shots. Recorded kinematic data of performed jump shots and the corresponding ground reaction forces were used to perform inverse dynamics. The calculated peak force of the LFTA (107 N) was found at maximum plantarflexion and of the LFTP (150 N) at maximum dorsiflexion. The peak force of the LFC (190 N) was observed at maximum dorsiflexion combined with maximum eversion. Within the performed jump shots, the LFTA showed a peak force (59 N to 69 N) during maximum plantarflexion in the final moment of the lift off. During landing, the force developed by the LFTA reached its peak value (61 N to 70 N) at the first contact with the floor. After that, the LFTP developed a peak force (70 N to 118 N). This model allows the calculation of forces in lateral ankle ligaments. The information obtained in this study can serve as a basis for future research on ankle sprain and ankle sprain simulation. PMID- 22074594 TI - Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems. AB - BACKGROUND: Understanding host response to influenza virus infection will facilitate development of better diagnoses and therapeutic interventions. Several different experimental models have been used as a proxy for human infection, including cell cultures derived from human cells, mice, and non-human primates. Each of these systems has been studied extensively in isolation, but little effort has been directed toward systematically characterizing the conservation of host response on a global level beyond known immune signaling cascades. RESULTS: In the present study, we employed a multivariate modeling approach to characterize and compare the transcriptional regulatory networks between these three model systems after infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Using this approach we identified functions and pathways that display similar behavior and/or regulation including the well studied impact on the interferon response and the inflammasome. Our results also suggest a primary response role for airway epithelial cells in initiating hypercytokinemia, which is thought to contribute to the pathogenesis of H5N1 viruses. We further demonstrate that we can use a transcriptional regulatory model from the human cell culture data to make highly accurate predictions about the behavior of important components of the innate immune system in tissues from whole organisms. CONCLUSIONS: This is the first demonstration of a global regulatory network modeling conserved host response between in vitro and in vivo models. PMID- 22074596 TI - Fun with photons, reactive intermediates, and friends. Skating on the edge of the paradigms of physical organic chemistry, organic supramolecular photochemistry, and spin chemistry. AB - This Perspective presents a review and survey of the science and philosophy of my research career over the past five decades at Columbia as a physical organic chemist and photochemist. I explore the role of paradigms, structure, and geometric thinking in my own cognitive and intellectual development. The Perspective describes my investigations of high energy content molecules in electronically excited states and the development of electronic spin and supramolecular photochemistry chemistry. Current research dealing with the nuclear spin chemistry of H(2) incarcerated in buckyballs is illustrated. In the second part of this Perspective, I recount a personal role of the philosophy and history of science and the scientific communities' use of paradigms in their every day research and intellectual activities. Examples are given of the crucial role of geometry and structure in the rapid development of organic chemistry and physical organic chemistry over the past century. PMID- 22074595 TI - Ambulatory high-resolution manometry, lower esophageal sphincter lift and transient lower esophageal sphincter relaxation. AB - BACKGROUND: Lower esophageal sphincter (LES) lift seen on high-resolution manometry (HRM) is a possible surrogate marker of the longitudinal muscle contraction of the esophagus. Recent studies suggest that longitudinal muscle contraction of the esophagus induces LES relaxation. AIM: Our goal was to determine: (i) the feasibility of prolonged ambulatory HRM and (ii) to detect LES lift with LES relaxation using ambulatory HRM color isobaric contour plots. METHODS: In vitro validation studies were performed to determine the accuracy of HRM technique in detecting axial movement of the LES. Eight healthy normal volunteers were studied using a custom designed HRM catheter and a 16 channel data recorder, in the ambulatory setting of subject's home environment. Color HRM plots were analyzed to determine the LES lift during swallow-induced LES relaxation as well as during complete and incomplete transient LES relaxations (TLESR). KEY RESULTS: Satisfactory recordings were obtained for 16 h in all subjects. LES lift was small (2 mm) in association with swallow-induced LES relaxation. LES lift could not be measured during complete TLESR as the LES is not identified on the HRM color isobaric contour plot once it is fully relaxed. On the other hand, LES lift, mean 8.4 +/- 0.6 mm, range: 4-18 mm was seen with incomplete TLESRs (n = 80). CONCLUSIONS & INFERENCES: Our study demonstrates the feasibility of prolonged ambulatory HRM recordings. Similar to a complete TLESR, longitudinal muscle contraction of the distal esophagus occurs during incomplete TLESRs, which can be detected by the HRM. Using prolonged ambulatory HRM, future studies may investigate the temporal correlation between abnormal longitudinal muscle contraction and esophageal symptoms. PMID- 22074597 TI - Usefulness of Forensic Dental Symbols(c) and Dental Encoder(c) database in forensic odontology. AB - A new universal graphic dental system, Forensic Dental Symbols((c)), has been created to provide precision in the construction of dental records, improve standardization, and increase efficiency in dental identification procedures. Two hundred and thirty-four different graphic symbols representing the most frequent clinical status for each tooth were designed. Symbols can be then converted to a typographic font and then are ready to use in any computer. For the appropriate use, manipulation, and storage of dental information generated by the Forensic Dental Symbols((c)), Dental Encoder((c)) database has been created. The database contains all the information required by INTERPOL Disaster Victim Identification (DVI)-dental-forms. To explore the possibilities that Dental Encoder((c)) offers, an antemortem dental database from a Spanish population of 3920 military personnel had been constructed. Data generated by Dental Encoder((c)) were classified into sex and age groups. The program can perform an automatic search of the database for cases that match a selected clinical status presented in a single tooth or a combination of situations for several teeth. Moreover, Dental Encoder((c)) allows information to be printed on INTERPOL DVI-dental-forms, or the inclusion of any completed form into any document, technical report, or identification of dental report. PMID- 22074598 TI - Uniaxial strain orientation dependence of superconducting transition temperature (Tc) and critical superconducting pressure (Pc) in beta-(BDA-TTP)2I3. AB - Dependence of the superconducting transition temperature (T(c)) and critial superconducting pressure (P(c)) of the pressure-induced superconductor beta-(BDA TTP)(2)I(3) [BDA-TTP = 2,5-bis(1,3-dithian-2-ylidene)-1,3,4,6-tetrathiapentalene] on the orientation of uniaxial strain has been investigated. On the basis of the overlap between the upper and lower bands in the energy dispersion curve, the pressure orientation is thought to change the half-filled band to the quarter filled one. The observed variations in T(c) and P(c) are explained by considering the degree of application of the pressure and the degree of contribution of the effective electronic correlation at uniaxial strains with different orientations parallel to the conducting donor layer. PMID- 22074599 TI - Phenotypic and genetic analyses of 111 clinical and environmental O1, O139, and non-O1/O139 Vibrio cholerae strains from different geographical areas. AB - A total of 111 clinical and environmental O1, O139 and non-O1/O139 Vibrio cholerae strains isolated between 1978 and 2008 from different geographical areas were typed using a combination of methods: antibiotic susceptibility, biochemical test, serogroup, serotype, biotype, sequences containing variable numbers of tandem repeats (VNTRs) and virulence genes ctxA and tcpA amplification. As a result of the performed typing work, the strains were organized into four clusters: cluster A1 included clinical O1 Ogawa and O139 serogroup strains (ctxA(+) and tcpA(+)); cluster A2 included clinical non-O1/O139 strains (ctxA(-) and tcpA(-)), as well as environmental O1 Inaba and non-O1/O139 strains (ctxA(-) and tcpA(-)/tcpA(+)); cluster B1 contained two clinical O1 strains and environmental non-O1/O139 strains (ctxA(-) and tcpA(+)/tcpA(-)); cluster B2 contained clinical O1 Inaba and Ogawa strains (ctxA(+) and tcpA(+)). The results of this work illustrate the advantage of combining several typing methods to discriminate between clinical and environmental V. cholerae strains. PMID- 22074601 TI - Wnt signaling signaling at and above the receptor level. AB - Wnt signaling is one of the most important developmental signaling pathways that controls cell fate decisions and tissue patterning during early embryonic and later development. It is activated by highly conserved Wnt proteins that are secreted as palmitoylated glycoproteins and act as morphogens to form a concentration gradient across a developing tissue. Wnt proteins regulate transcriptional and posttranscriptional processes depending on the distance of their origin and activate distinct intracellular cascades, commonly referred to as canonical (beta-catenin-dependent) and noncanonical (beta-catenin-independent) pathways. Therefore, the secretion and the diffusion of Wnt proteins needs to be tightly regulated to induce short- and long-range downstream signaling. Even though the Wnt signaling cascade has been studied intensively, key aspects and principle mechanisms, such as transport of Wnt growth factors or regulation of signaling specificity between different Wnt pathways, remain unresolved. Here, we introduce basic principles of Wnt/Wg signal transduction and highlight recent discoveries, such as the involvement of vacuolar ATPases and vesicular acidification in Wnt signaling. We also discuss recent findings regarding posttranslational modifications of Wnts, trafficking through the secretory pathway and developmental consequences of impaired Wnt secretion. Understanding the detailed mechanism and regulation of Wnt protein secretion will provide valuable insights into many human diseases based on overactivated Wnt signaling. PMID- 22074602 TI - Notch-independent functions of CSL. AB - Notch-dependent CSL transcription complexes control essential biological processes such as cell proliferation, differentiation, and cell-fate decisions in diverse developmental systems. The orthologous proteins CBF1/Rbpj (mammalian), Su(H) (Drosophila), and Lag-1 (Caenorhabditis elegans) compose the CSL family of sequence-specific DNA-binding transcription factors. The CSL proteins are best known for their role in canonical Notch signaling. However, CSL factors also form transcription complexes that can function independent of Notch signaling and include repression and activation of target gene transcription. Because the different complexes share CSL as a DNA-binding subunit, they can control overlapping sets of genes; but they can also control distinct sets when partnered with tissue-specific cofactors that restrict DNA-sequence recognition or stability of the DNA-bound complex. The Notch-independent functions of CSL and the processes they regulate will be reviewed here with a particular emphasis on the tissue-specific CSL-activator complex with the bHLH factor Ptf1a. PMID- 22074600 TI - New insights into signaling during myelination in zebrafish. AB - Myelin is a vertebrate adaptation that allows for the rapid propagation of action potentials along axons. Specialized glial cells-oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS) form myelin by repeatedly wrapping axon segments. Debilitating diseases result from the disruption of myelin, including multiple sclerosis and Charcot-Marie Tooth peripheral neuropathies. The process of myelination involves extensive communication between glial cells and the associated neurons. The past few years have seen important progress in understanding the molecular basis of the signals that coordinate the development of these fascinating cells. This review highlights recent advances in myelination deriving from studies in the zebrafish model system, with a primary focus on the PNS. While Neuregulin1-ErbB signaling has long been known to play important roles in peripheral myelin development, work in zebrafish has elucidated its roles in Schwann cell migration and radial sorting of axons in vivo. Forward genetic screens in zebrafish have also uncovered new genes required for development of myelinated axons, including gpr126, which encodes a G-protein coupled receptor required for Schwann cells to progress beyond the promyelinating stage. In addition, work in zebrafish uncovered new roles for Schwann cells themselves, including in regulating the boundary between the PNS and CNS and positioning a nerve after its initial outgrowth. PMID- 22074603 TI - Sonic hedgehog signaling in the developing CNS where it has been and where it is going. AB - Sonic Hedgehog (Shh) is one of three mammalian orthologs of the Hedgehog (Hh) family of secreted proteins first identified for their role in patterning the Drosophila embryo. In this review, we will highlight some of the outstanding questions regarding how Shh signaling controls embryonic development. We will mainly consider its role in the developing mammalian central nervous system (CNS) where the pathway plays a critical role in orchestrating the specification of distinct cell fates within ventral regions, a process of exquisite complexity that is necessary for the proper wiring and hence function of the mature system. Embryonic development is a process that plays out in both the spatial and the temporal dimensions, and it is becoming increasingly clear that our understanding of Shh signaling in the CNS is grounded in an appreciation for the dynamic nature of this process. In addition, any consideration of Hh signaling must by necessity include a consideration of data from many different model organisms and systems. In many cases, the extent to which insights gained from these studies are applicable to the CNS remains to be determined, yet they provide a strong framework in which to explore its role in CNS development. We will also discuss how Shh controls cell fate diversification through the regulation of patterned target gene expression in the spinal cord, a region where our understanding of the morphogenetic action of graded Shh signaling is perhaps the furthest advanced. PMID- 22074605 TI - Signaling pathways and axis formation in the lower metazoa. AB - The determination of the body axis in the last common ancestor of bilaterian animals is still a matter of debate. While Hox genes pattern the formation of the primary, anteroposterior body axis in bilaterians, there is growing evidence from lower metazoans that the Wnt/beta-catenin pathway acts as the primordial signaling system in this process. This review summarizes molecular data from recent genomic analyses of basal model organisms with a focus on the evolution of signaling pathways involved in the establishment of the primary and successive body axes during early metazoan evolution. PMID- 22074604 TI - Activity-mediated synapse formation a role for Wnt-Fz signaling. AB - Synapse formation is a critical step in the assembly of neuronal circuits. Both secreted and membrane-associated proteins contribute to the assembly and maturation of synapses. In addition, neuronal activity regulates the formation of neuronal circuits through the stimulation of growth factor secretion and the localization of receptors such as NMDA and AMPA receptors (NMDAR and AMPAR, respectively). Little is known, however, about the role of activity in the localization and function of receptors for synaptogenic molecules. Wnts are secreted proteins that play a role in synapse formation by regulating pre- and postsynaptic assembly at central and peripheral synapses. Wnts can signal through different receptors including Frizzleds (Fzs), the LRP5/6 coreceptors, Ror and Ryk. Fz receptors have been shown to mediate Wnt function during synapse formation. At the cell surface, Fz receptors are located at synaptic and extrasynaptic sites. Importantly, synaptic localization of Fzs is regulated by neuronal activity in a Wnt-dependent manner. In this review, we discuss the function of Wnt-Fz signaling in the assembly of central and peripheral synapses and the evidence supporting a role for Wnt ligands and their Fz receptors in activity-mediated synapse formation. PMID- 22074606 TI - FGF and ROR2 receptor tyrosine kinase signaling in human skeletal development. AB - Skeletal malformations are among the most frequent developmental disturbances in humans. In the past years, progress has been made in unraveling the molecular mechanisms that govern skeletal development by the use of animal models as well as by the identification of numerous mutations that cause human skeletal syndromes. Receptor tyrosine kinases have critical roles in embryonic development. During formation of the skeletal system, the fibroblast growth factor receptor (FGFR) family plays major roles in the formation of cranial, axial, and appendicular bones. Another player of relevance to skeletal development is the unusual receptor tyrosine kinase ROR2, the function of which is as interesting as it is complex. In this chapter, we review the involvement of FGFR signaling in human skeletal disease and provide an update on the growing knowledge of ROR2. PMID- 22074607 TI - Signaling between cells. Preface. PMID- 22074608 TI - Characterization of flavonol glycosides in individual Arabidopsis root tips by flow injection electrospray mass spectrometry. AB - Developments in mass spectrometry-based technologies are offering insights into the complexity and dynamic nature of plant metabolism. However, the ability to generate reliable metabolic profiles at high spatial resolution is still limited by the need of most technologies for large sample sizes or time-intensive extraction and detection methods. Here we describe the use of flow injection electrospray mass spectrometry for the rapid identification and semi-quantitative analysis of flavonol glycosides in individual root tips. This method uncovered spatial and temporal differences in metabolic profiles that were masked in analyses of whole roots or seedlings, while showing that individual biological replicates can be extremely consistent. PMID- 22074609 TI - 2D versus 3D imaging of hip displacement in children with cerebral palsy. PMID- 22074610 TI - Methodological quality of economic evaluations of new pharmaceuticals in The Netherlands. AB - BACKGROUND: In the Netherlands, decisions about the reimbursement of new pharmaceuticals are based on cost effectiveness, as well as therapeutic value and budget impact. Since 1 January 2005, drug manufacturers are formally required to substantiate the cost effectiveness of drugs that have therapeutic added value in comparison with existing ones through pharmacoeconomic evaluations. Dutch guidelines for pharmacoeconomic research provide methods guidance, ensuring consistency in both the evidence and the decision-making process about drug reimbursement. AIM: This study reviewed the methodological quality of all 21 formally required pharmacoeconomic evaluations of new pharmaceuticals between 1 January 2005 and 1 October 2008, and verified whether these evaluations complied with pharmacoeconomic guidelines. METHODS: Data on the quality of the pharmacoeconomic evaluations were extracted from the pharmacoeconomic reports published by the Dutch Health Care Insurance Board (CVZ). The Board's newsletters provided information on the advice to, and reimbursement decisions made by, the Dutch Minister of Health. All data extraction was carried out by two independent reviewers, and descriptive analyses were conducted. RESULTS: The methodological quality was sound in only 8 of the 21 pharmacoeconomic evaluations. In most cases, the perspective of analysis, the comparator drugs, and the reporting of both total and incremental costs and effects were correct. However, drug indication, form (i.e. cost utility/cost effectiveness) and time horizon of the evaluations were frequently flawed. Moreover, the costs and effects of the pharmaceuticals were not always analysed correctly, and modelling studies were often non-transparent. Twelve drugs were reimbursed, and nine were not. CONCLUSIONS: The compliance with pharmacoeconomic guidelines in economic evaluations of new pharmaceuticals can be improved. This would improve the methodological quality of the pharmacoeconomic evaluations and ensure consistency in the evidence and the decision-making process for drug reimbursement in the Netherlands. PMID- 22074611 TI - Reply to: Implicit memory in schizophrenia: the problem that will not go away. PMID- 22074612 TI - Altered cell cycle dynamics in schizophrenia. AB - BACKGROUND: The olfactory mucosa, the organ of smell in the nose, is a neural tissue that regenerates new sensory neurons throughout adult life. Based on this tissue, we previously demonstrated increased mitosis in olfactory biopsy cultures from schizophrenia patients compared with healthy control subjects. In addition, neural stem/progenitor cell cultures (neurosphere-derived cells) from nasal biopsies from individuals with schizophrenia show significantly altered gene and protein expression in key cell cycle control pathways. METHODS: The aim of this study was to investigate cell cycle dynamics in olfactory neurosphere-derived cells from nine male schizophrenia patients and nine male healthy control subjects. Cell cycles were arrested by serum deprivation after which cell population doubling time, proliferation fraction, and cell cycle period were calculated from cell counts over 96 hours. Cell cycle phase was investigated using flow cytometry. Cell lysates were analyzed for expression of cyclin proteins. RESULTS: Cell population proliferation rate was increased in schizophrenia through a larger pool of proliferating progenitors and a reduced cell cycle period. All phases of the cell cycle were phase-shifted by 2 hours in the schizophrenia-derived cells, which expressed higher levels of the cyclins D1, E, and A2. CONCLUSIONS: Our observations indicate that schizophrenia is associated with subtle alterations in cell cycle dynamics, shortening of the cell cycle period, and increased expression of G1/S phase cyclins. We speculate that this underlying diathesis could alter the temporal and spatial cascade of brain development and contribute to an altered neurodevelopmental trajectory in schizophrenia. PMID- 22074613 TI - Several clinical interests regarding lung volume reduction surgery for severe emphysema: meta-analysis and systematic review of randomized controlled trials. AB - OBJECTIVES: We aim to address several clinical interests regarding lung volume reduction surgery (LVRS) for severe emphysema using meta-analysis and systematic review of randomized controlled trials (RCTs). METHODS: Eight RCTs published from 1999 to 2010 were identified and synthesized to compare the efficacy and safety of LVRS vs conservative medical therapy. One RCT was obtained regarding comparison of median sternotomy (MS) and video-assisted thoracoscopic surgery (VATS). And three RCTs were available evaluating clinical efficacy of using bovine pericardium for buttressing, autologous fibrin sealant and BioGlue, respectively. RESULTS: Odds ratio (95%CI), expressed as the mortality of group A (the group underwent LVRS) versus group B (conservative medical therapies), was 5.16(2.84, 9.35) in 3 months, 3(0.94, 9.57) in 6 months, 1.05(0.82, 1.33) in 12 months, respectively. On the 3rd, 6th and 12th month, all lung function indices of group A were improved more significantly as compared with group B. PaO2 and PaCO2 on the 6th and 12th month showed the same trend. 6MWD of group A on the 6th month and 12th month were improved significantly than of group B, despite no difference on the 3rd month. Quality of life (QOL) of group A was better than of group B in 6 and 12 months. VATS is preferred to MS, due to the earlier recovery and lower cost. And autologous fibrin sealant and BioGlue seems to be the efficacious methods to reduce air leak following LVRS. CONCLUSIONS: LVRS offers the more benefits regarding survival, lung function, gas exchange, exercise capacity and QOL, despite the higher mortality in initial three postoperative months. LVRS, with the optimization of surgical approach and material for reinforcement of the staple lines, should be recommended to patients suffering from severe heterogeneous emphysema. PMID- 22074615 TI - The effect of administrative cessation of the use of ipratropium bromide in the treatment of acute asthma attacks in the emergency department. AB - BACKGROUND: The anticholinergic agent ipratropium bromide has demonstrated effectiveness in the treatment of severe asthma exacerbations. METHODS: We conducted a retrospective quasi-experiment to investigate the clinical consequences on acute asthma patients of the administrative removal of ipratropium bromide from an emergency department (ED) of a large tertiary hospital. We compared the combined negative outcome (hospitalization, length of stay in the ED, hospital readmission within 48 hours or 7 days, intubation, and death) of acute asthma patients, treated in the 12 months preceding (n = 394; Period A) and the 12 months following (n = 334; Period B) the policy change. Multiple imputations based on sequentially improved regressions were performed for missing data on measures of severity. RESULTS: Administration of steroid medications increased from 49.8% to 61.4%; p = .002 from Period A to Period B. There was no statistically significant difference in combined negative outcome between Periods A and B (41.1% and 42.9%, respectively). CONCLUSIONS: An administrative decision to stop the purchase of ipratropium bromide in an ED was followed by an increased use of steroids; adverse consequences did not increase in acute asthmatic patients. In the absence of ipratropium bromide in the ED, steroids may thus serve as an appropriate substitute, an observation that calls for a randomized controlled clinical trial. PMID- 22074614 TI - Evaluation of the implementation of an integrated primary care network for prevention and management of cardiometabolic risk in Montreal. AB - BACKGROUND: The goal of this project is to evaluate the implementation of an integrated and interdisciplinary program for prevention and management of cardiometabolic risk (PCMR). The intervention is based on the Chronic Care Model. The study will evaluate the implementation of the PCMR in 6 of the 12 health and social services centres (CSSS) in Montreal, and the effects of the PCMR on patients and the practice of their primary care physicians up to 40 months following implementation, as well as the sustainability of the program. Objectives are: 1-to evaluate the effects of the PCMR and their persistence on patients registered in the program and the practice of their primary care physicians, by implementation site and degree of exposure to the program; 2-to assess the degree of implementation of PCMR in each CSSS territory and identify related contextual factors; 3-to establish the relationships between the effects observed, the degree of PCMR implementation and the related contextual factors; 4 to assess the impact of the PCMR on strengthening local services networks. METHODS/DESIGN: The evaluation will use a mixed design that includes two complementary research strategies. The first strategy is similar to a quasi experimental "before-after" design, based on a quantitative approach; it will look at the program's effects and their variations among the six territories. The effects analysis will use data from a clinical database and from questionnaires completed by participating patients and physicians. Over 3000 patients will be recruited. The second strategy corresponds to a multiple case study approach, where each of the six CSSS constitutes a case. With this strategy, qualitative methods will set out the context of implementation using data from semi structured interviews with program managers. The quantitative data will be analyzed using linear or multilevel models complemented with an interpretive approach to qualitative data analysis. DISCUSSION: Our study will identify contextual factors associated with the effectiveness, successful implementation and sustainability of such a program. The contextual information will enable us to extrapolate our results to other contexts with similar conditions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01326130. PMID- 22074616 TI - Comparative study of direct and phase-specific vibrational sum-frequency generation spectroscopy: advantages and limitations. AB - As a surface-specific technique, vibrational sum-frequency generation (SFG) is used in a wide range of applications where soft matter or solid interfaces are to be probed on a molecular level through their vibrational modes. In recent years, phase-specific sum-frequency generation (PS-SFG, also known as heterodyne detected SFG) spectroscopy has been increasingly replacing its predecessor (direct SFG, also known as homodyne SFG) as the experimental technique of choice for characterizing interfacial structure. The technique enables phase sensitive measurements, allowing for the determination of the real and imaginary parts of the interfacial vibrational response function and thereby the unambiguous identification of molecular orientation. This phase-sensitivity requires, however, a complete understanding of the complex optical properties of the sample and of their effect on the signal. These optical properties significantly influence the raw spectral data from which the real and imaginary parts of the second-order susceptibility are retrieved. We show that it is essential to correct the data appropriately to infer the true molecular response. The current study presents a detailed description of the physical contributions to the phase resolved spectrum, allowing a direct comparison between the phase-resolved spectrum and that obtained using the well-understood direct detection method in a step-by-step data analysis process. In addition to phase sensitivity, PS-SFG has been shown to increase the sensitivity compared to traditional (direct) SFG spectroscopy. We present a quantitative comparison between theoretical limits of the signal-to-noise ratio of both techniques, which shows that for many systems the signal-to-noise ratio is very similar for direct- and phase-specific SFG signals. PMID- 22074617 TI - To live as mentally disabled in the risk society. AB - The contemporary society is to some extent characterized by longitudinal changes, towards individualization, uncertainty, and risk. Numerous risks and dangers in modern society have been mastered, while others have emerged, often created by human actions. The individual's freedom of choice has increased, but also the responsibility for the choices made. In this society, the risk society, there is a greater need for formative and situation-related knowledge to manage risks. The aims of this paper are to discuss the concept of risk society in the light of everyday experiences made by people with mental disabilities, how challenges can be mastered and positive possibilities can be utilized. Data collection was made through a multistage focus group, and the data were analysed by qualitative content analysis. The results show that characteristics of the risk society are identified by people with mental disabilities. Change and uncertainty, obstacles created by societal institutions, lack of trust, and the need of adapted working conditions are frequently experienced, impersonal relations and feelings of loneliness as well. However, these conditions can be partly counteracted by belonging to an alternative fellowship, which might lead to quality of life related personal improvements. PMID- 22074619 TI - Treatment of meniscus tears during anterior cruciate ligament reconstruction. AB - PURPOSE: To define the incidence of meniscectomy, meniscus repair, and meniscus tears left in situ during anterior cruciate ligament (ACL) reconstruction. METHODS: A systematic search of PubMed and 7 sports medicine journal databases was performed to determine the treatment of meniscus tears during ACL reconstruction. Inclusion criteria were English language, publication in the last 10 years, clinical trials, all evidence levels, and skeletally mature or immature knees. Exclusion criteria were revision ACL reconstruction, concomitant ligament reconstruction, and studies with exclusion or inclusion criteria regarding meniscus surgery during ACL reconstruction. RESULTS: Of 634 articles identified, 159 met the inclusion criteria, encompassing 19,531 patients. There were 11,711 meniscus tears; they were treated by meniscectomy in 65% (7,621 tears), treated by repair in 26% (3,022 tears), or left in situ in 9% (1,068 tears). Only 19 studies analyzed the treatment of meniscus tears according to the tibiofemoral compartment. These reported medial compartment tears were treated by meniscectomy in 63%, treated by repair in 27%, and left in situ in 9%. Lateral compartment tears were treated by meniscectomy in 71%, treated by repair in 14%, and left in situ in 14%. Only 24 studies identified the type of meniscus repair procedure performed. In 33 studies (21%) repair was performed more frequently than meniscectomy. CONCLUSIONS: Meniscectomy is performed 2 to 3 times more frequently than meniscus repair during ACL reconstruction. We were unable to analyze the effect of the location and type of meniscus tear, sex, age, or chronicity of injury on the treatment of meniscus tears. The number of potentially repairable meniscus tears that were treated by resection could not be identified. CLINICAL RELEVANCE: This study found that meniscectomy was performed in 65% of meniscus tears. This is concerning because studies have shown that, regardless of knee stability obtained after ACL reconstruction, meniscectomy accelerates degenerative joint changes. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies. PMID- 22074618 TI - DRACMA one year after: which changes have occurred in diagnosis and treatment of CMA in Italy? PMID- 22074620 TI - Dynamic contact mechanics of radial tears of the lateral meniscus: implications for treatment. AB - PURPOSE: To characterize the effect of radial tears (RTs) of the lateral meniscus and their subsequent treatment (inside-out repair, partial meniscectomy) on joint contact mechanics during simulated gait. METHODS: Six human cadaveric knees were mounted on a simulator programmed to mimic human gait. A sensor was inserted below the lateral meniscus to measure peak joint contact pressure location, magnitude, and contact area. The following conditions were compared: intact meniscus, 30% RT (at the popliteal hiatus), 60% RT, 90% RT, repair, and partial meniscectomy. Data were analyzed in the midstance phase of gait (14% and 45%) when axial force was at its highest (2,100 N). RESULTS: Intact knees had peak contact pressures of 5.9 +/- 0.9 MPa and 6.4 +/- 1.1 MPa at 14% and 45% of gait, respectively. RTs of up to and including 60% had no effect on pressure magnitude or location. RTs of 90% resulted in significantly increased peak pressure (8.4 +/ 1.1 MPa) in the postero-peripheral aspect of the tibial plateau and reduced contact area versus the intact knee, at 45% of gait. Repair resulted in a significant decrease in peak pressure (7.7 +/- 1.0 MPa) relative to 90% RT but had no effect on contact area. Partial lateral meniscectomy resulted in areas and pressures that were not significantly different from 90% tears (8.7 +/- 1.5 MPa). CONCLUSIONS: Simulated large RTs of the lateral meniscus in the region of the popliteal hiatus show unfavorable dynamic contact mechanics that are not significantly different from those resulting from a partial lateral meniscectomy. Pressure was significantly reduced with inside-out repair but was not affected by partial meniscectomy; contact area was not restored to that of the intact condition for either procedure. CLINICAL RELEVANCE: Large RTs in the region of the popliteal hiatus show unfavorable dynamic contact mechanics. PMID- 22074621 TI - Cellular therapies supplement: the peritoneum as an ectopic site of hematopoiesis following in utero transplantation. AB - BACKGROUND: In utero transplantation (IUT) has the potential to treat birth defects early before full development of the immune system. Relatively small grafts, which are not matched for major histocompatibility antigens, can be delivered even before onset of disease symptoms. IUT of hematopoietic stem cells is usually performed via intraperitoneal injection, yet the fate of donor cells in the peritoneal cavity is not fully understood. We review our recent work and present new data demonstrating that the peritoneum can be a site of ectopic hematopoiesis with implications for IUT and immune tolerance induction. STUDY DESIGN AND METHODS: Haplogeneic and allogeneic fetal transplants were performed in mice and engraftment tracked by flow cytometry. Immune tolerance was studied by mixed lymphocyte reactions and skin transplantation. Adult syngeneic murine transplants and xenogeneic human into immunodeficient mouse transplants were performed to follow hematopoietic retention in the peritoneum and engraftment of the marrow. RESULTS: Although most transplanted cells rapidly clear the peritoneum, hematopoietic cells and cells with the phenotype of hematopoietic precursors can remain in the peritoneal cavity for months after transplant. The presence of donor cells in the peritoneum can contribute to donor-specific tolerance, but sufficient peripheral blood chimerism is required to ensure acceptance of donor skin grafts. CONCLUSION: Ectopic hematopoiesis and the survival of stem cells in the peritoneum offer the possibility of better using the peritoneal cavity to delivery stem cells and foster the development of immune tolerance to alloantigens or other foreign antigens. PMID- 22074622 TI - Understanding the first steps in embryonic stem cell exit from the pluripotent state. AB - BACKGROUND: We are interested in understanding how a given cell type, in response to external cues from its environment, makes the decision to differentiate. In the case of mouse embryonic stem cells (mESCs), the key external factor that maintains their undifferentiated state is the cytokine leukemia inhibitory factor (LIF). LIF removal causes mESCs to exit their pluripotent state and differentiate into more restricted precursors. Although LIF is known to activate multiple different phosphorylation cascades, the mechanisms by which its removal leads to mESC differentiation are not well understood. STUDY DESIGN AND METHODS: In order to identify the molecular events that occur upon LIF removal, we developed a set of novel experimental approaches that allowed identification and quantification of global phosphorylation changes that occur when mESCs are deprived of LIF. These included growth of mESCs on permeable membranes and development of a robust and sensitive phospho-proteomics platform to quantify early signaling events. RESULTS: In addition to the well-characterized tyrosine 705 phosphorylation of STAT3, LIF removal results in the rapid phosphorylation of multiple other proteins known to regulate the mESC self-renewal on both tyrosine, serine, and threonine residues. We hypothesize that these unique posttranslational modifications help drive the exit of mESCs from the pluripotent state. CONCLUSIONS: Our data set the stage for future studies investigating the functional role of these phosphorylation events in mESCs. These studies were greatly facilitated by the National Blood Foundation, whose support in the crucial initiation phase of these studies was invaluable. PMID- 22074623 TI - Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics. AB - The field of hematopoietic stem cell transplantation (HSCT) has overcome many obstacles that have led to our current clinical ability to utilize cells collected from marrow, mobilized peripheral blood, or umbilical cord blood for the treatment of malignant and nonmalignant hematologic diseases. It is in this context that it becomes evident that future progress will lie in our development of an understanding of the biology by which the process of HSCT is regulated. By understanding the cellular components and the mechanisms by which HSCT is either enhanced or suppressed it will then be possible to design therapeutic strategies to improve rates of engraftment that will have a positive impact on immune reconstitution post-HSCT. In this review we focus primarily on allogeneic hematopoietic stem cell transplantation (allo-HSCT), the current challenges associated with allo-HSCT, and some developing strategies to improve engraftment in this setting. PMID- 22074624 TI - Human embryonic stem cell-derived mesenchymal stromal cells. AB - Mesenchymal stromal cells (MSCs) originally isolated from marrow have multipotent differentiation potential and favorable immunomodulatory and anti-inflammatory properties that make them very attractive for regenerative cellular therapy. Cells with similar phenotypic characteristics have now been derived from almost all fetal, neonatal, and adult tissues; furthermore, more recently similar cells have also been generated from human embryonic stem cells (ESCs). Generation of MSCs from human ESCs provides an opportunity to study the developmental biology of human mesenchymal lineage generation in vitro. Generation of bone and cartilage from human ESC-derived MSCs and their functional characterization, both in vitro and in vivo, is also an active area of investigation as ESCs could provide an unlimited source of MSCs for potential repair of bone and cartilage defects. MSCs from adult sources are being investigated in numerous Phase I-III clinical trials for a wide variety of indications, mainly based on their immunomodulatory properties. Our group and others have shown MSCs derived from human ESCs possess immunomodulatory properties similar to marrow-derived MSCs. Immunomodulatory properties of ESC-derived MSCs could prove to be highly valuable for their potential clinical applications in the future as derivatives of human ESCs have already entered clinical arena in the context of Phase I clinical trials. PMID- 22074625 TI - Production of cytotoxic, KIR-negative NK cells from CD34+ cord blood cells with the use of Notch signaling. AB - The use of natural killer (NK) cells as cell therapy against acute leukemia is an active area of investigation. The optimal source of cytotoxic NK cells for therapeutic use is presently unknown. With funds from the National Blood Foundation, the author's lab has developed in vitro culture systems that use the Notch receptor ligand Delta4 for the differentiation and expansion of functional NK cells from CD34+ cord blood hematopoietic progenitor cells. These Notch induced NK (N-NK) cells display a predominantly immature, CD56(bright) surface phenotype, with expression of activating receptors important for leukemia cell recognition and killing, but with an absence of inhibitory receptors that bind major histocompatibility complex (MHC) class I, making them free of restriction by self-MHC. They are capable of directly killing hematopoietic tumor cell lines and primary leukemia cells in vitro. Thus, cytotoxic, HLA-independent N-NK cells may represent a novel cell therapy for hematopoietic malignancy. PMID- 22074626 TI - On how Rac controls hematopoietic stem cell activity. AB - Rac GTPases form part of the family of Rho small GTPases. Rac GTPases, like other Rho family GTPases, are key molecular switches controlling the transduction of external signals to cytoplasmic and nuclear effectors. The development of genetic and pharmacological tools has allowed a more precise definition of the specific roles of Rac GTPases in hematopoietic stem cells (HSCs). Our current knowledge has enabled dissection of their specific and redundant roles. Rac GTPases are now known to be crucial in the response of HSCs to the hematopoietic microenvironment cues. This review will briefly summarize the known HSC functions that are regulated by Rac GTPases, focusing on adhesion, migration, retention, proliferation, and survival, and how Rac relates to the physiological functions of HSC. The development of small molecule inhibitors with the ability to interfere with Rac GTPase activation offers new therapeutic strategies to manipulate the function of HSC in vivo and ex vivo. PMID- 22074627 TI - Cellular therapies supplement: the role of granulocyte macrophage colony stimulating factor and dendritic cells in regulatory T-cell homeostasis and expansion. AB - Regulatory T cells are a subset of T cells with inhibitory function that are critical for protection against autoimmunity and immunopathology. A failure to maintain adequate regulatory T-cell numbers in the periphery results in autoimmune manifestations, highlighting the importance of the continuous maintenance of peripheral regulatory T cells. The cellular and molecular requirements for regulatory T-cell homeostasis and expansion are not fully understood but involve a complex interplay among dendritic cells, conventional T cells, and regulatory T cells. In addition, soluble factors such as the cytokine granulocyte macrophage colony-stimulating factor may play a role in enhancing these interactions. In this review, we discuss our National Blood Foundation funded studies relating to the role of granulocyte macrophage colony-stimulating factor and dendritic cells in controlling regulatory T-cell homeostasis and expansion. PMID- 22074628 TI - A journey to produce platelets in vitro. AB - Allogeneic platelet transfusions protect patients from bleeding episodes and also make aggressive medical procedures such as those involving marrow transplants requiring chemotherapy and/or radiotherapy possible. These patients are dependent upon an unfailing supply of platelets that can sometimes be in short supply due to high demands coupled with an extremely short expiration date for platelet products of only 5 days. One approach that is under investigation to overcome platelet shortages is to harness the extraordinary capabilities of stem cells to proliferate and differentiate into various cell types and to use this ability to specifically produce clinical scale quantities of functional platelets in bioreactors. To accomplish such an enormous and complex task requires an appreciation of the regulatory mechanisms that occur during the development of megakaryocytes (MKs) and the subsequent biogenesis of functional platelets from mature MKs. This means understanding the complex network of intracellular and extracellular regulatory mechanisms that act at each phase of a developmental process that ushers stem cells along the MK lineage to produce billions of platelets per day in a healthy individual. PMID- 22074629 TI - Regulation of hematopoietic stem cell trafficking and mobilization by the endocannabinoid system. AB - The cannabinoid receptors CB(1) and CB(2) are seven-transmembrane Galphai protein-coupled receptors and are expressed in certain mature hematopoietic cells. We recently showed that these receptors are expressed in murine and human hematopoietic stem cells (HSCs) and that CB(2) agonists induced chemotaxis, enhanced colony formation of marrow cells, as well as caused in vivo mobilization of murine HSCs with short- and long-term repopulating abilities. Based on these observations, we have further explored the role of CB(2) and its agonist AM1241 on hematopoietic recovery following sublethal irradiation in mice. Cannabinoid receptor 2 knockout mice (Cnr2(-/-) deficient mice) exhibited impaired recovery following sublethal irradiation as compared with irradiated wild-type (WT) mice, as determined by low colony-forming units and low peripheral blood counts. WT mice treated with CB(2) agonist AM1241 following sublethal irradiation demonstrated accelerated marrow recovery and increased total marrow cells (approximately twofold) and total lineage- c-kit(+) cells (approximately sevenfold) as well as enhanced HSC survival as compared with vehicle control treated mice. When the CB(2) agonist AM1241 was administered to WT mice 12 days before their sublethal irradiation, analysis of hematopoiesis in these mice showed decreased apoptosis of HSCs, enhanced survival of HSCs, as well as increase in total marrow cells and c-kit+ cells in the marrow. Thus, CB(2) agonist AM1241 promoted recovery after sublethal irradiation by inhibiting apoptosis of HSCs and promoting survival, as well as enhancing the number of HSCs entering the cell cycle. PMID- 22074630 TI - Cellular-based therapies to prevent or reduce thrombocytopenia. AB - BACKGROUND: Thrombocytopenia is a serious side effect following high-dose chemotherapy or whole-body irradiation. For many patients, a hematopoietic stem cell (HSC) transplant is required as part of the treatment or to restore the integrity of the hematopoietic system. In this article, we first review the origin of thrombocytopenia in the context of umbilical cord blood (UCB) transplantation and current cellular therapies developed to overcome this condition. Results obtained in recent clinical trials and in the laboratory using a mouse-based xenograft model were also discussed. Second, we investigate the kinetic of human platelet production in two immunodeficient mouse strains transplanted with UCB cells to determine which of the two is better suited to measure the thrombopoietic potential of human hematopoietic cells. STUDY DESIGN AND METHODS: NOD/SCID/IL2Rgamma(null) or NOD.CB17-Prkdcscid/NcrCrl (NOD/SCID) mice were transplanted with ex vivo expanded UCB cells. Human platelet levels and marrow engraftments were measured by cytometry analyses. RESULTS: Human platelets appeared earlier and at greater levels in the NOD/SCID/IL2Rgamma(null) mouse strain. Consistent with these results and previous reports, human marrow engraftment was also greater in the IL2Rgamma(null) -based NOD/SCID mice. CONCLUSION: The NOD/SCID/IL2Rgamma(null) mouse strain is an ideal choice for preclinical studies aimed at measuring the in vivo thrombopoietic potential of human HPCs. Exploitation of such a model should facilitate the development of new cellular therapies aimed at improving hematological recoveries following HSC transplantation. PMID- 22074631 TI - Advancing the preservation of cellular therapy products. AB - Cell therapies are typically collected in one location, processed in a second location, and then administered in a third location. The ability to preserve the cells is critical to their clinical application. It improves patient access to therapies by increasing the genetic diversity of cells available. In addition, the ability to preserve cells improves the "manufacturability" of a cell therapy product by permitting the cells to be stored until the patient is ready for administration of the therapy, permitting inventory control of products, and improving management of staffing at cell therapy facilities. Finally, the ability to preserve cell therapies improves the safety of cell therapy products by extending the shelf life of a product and permitting completion of safety and quality control testing before release of the product for use. The support of the National Blood Foundation has been critical to our work on improving the quality of frozen and thawed cell therapy products through the development of a microfluidic device to remove dimethlysulfoxide (DMSO). We are also involved in research to replace DMSO with other agents that are less toxic to cells and patients. Finally, the need to advance the preservation of cell therapies was a driving force behind the development of the Biopreservation Core Resource (http://www.biocor.net), a national resource in biopreservation. New interest in translation of cell therapies from the bench to the patient's bedside has the potential to drive the transformation of preservation science, technology, and practice. PMID- 22074632 TI - The role of HSAL (SALL) genes in proliferation and differentiation in normal hematopoiesis and leukemogenesis. AB - The National Blood Foundation (NBF) support was critical in the author's research career development. The NBF support came in the form of a start-up seed grant that she got from the American Association of Blood Banks, an organization that advances the practice and standards of transfusion medicine and cellular therapies and an organization in which she is a proud member. The NBF grant enabled her to keep up with her transfusion medicine practice while pursuing her passion to be a physician scientist. During its funding period, she was able to obtain critical preliminary bench data and to secure several National Institutes of Health grants with over a million dollars direct cost. In addition, the knowledge gained from the NBF-supported projects is currently being translated into medical practice in her lab by testing on cord blood expansion. She is looking forward to spending the upcoming years of her professional career bridging bedside observations on transfusion medicine with bench experiences and then utilizing that bench-derived knowledge in the practice of transfusion medicine. PMID- 22074633 TI - Human placenta and chorion: potential additional sources of hematopoietic stem cells for transplantation. AB - BACKGROUND: Hematopoietic stem cell (HSC) transplantation is an essential element of medical therapy, leading to cures of previously incurable hematological and nonhematological diseases. Many patients do not find matched donors in a timely manner, which has driven efforts to find alternative pools of transplantable HSCs. The use of umbilical cord blood (UCB) as a source of transplantable HSCs began more than two decades ago. However, the use of UCB as a reliable source of HSCs for transplantation still faces crucial challenges: the number of HSCs present in a unit of UCB is usually sufficient for younger children but not for adults, and the persistent delayed engraftment often seen can result in high rates of infection and mortality. STUDY DESIGN AND METHODS: We propose a new approach to a solution of these problems: a potential increase of the limited number of UCB-HSCs available by harvesting HSCs contained in the placenta and the fetal chorionic membrane available at birth. RESULTS: We investigated the presence of hematopoietic progenitors and HSCs in human placenta and chorion at different gestational ages. The characterization of these cells was performed by flow cytometry and immunolocalization, and their functional status was investigated by transplanting them into immunodeficient mice. CONCLUSION: HSCs are present in extraembryonic tissues and could be banked in conjunction to the UCB-HSCs. This novel approach could have a large impact on the field of HSC banking and, more crucially, on the outcome of patients undergoing this treatment by greatly improving the use of life-saving hematopoietic transplants. PMID- 22074635 TI - Reversible cerebral vasoconstriction syndrome in a patient taking citalopram and Hydroxycut: a case report. AB - INTRODUCTION: Reversible cerebral vasoconstriction syndrome presents with thunderclap headaches accompanied by mild neurologic deficits and is characterized by multifocal narrowing of the cerebral arteries that resolves over days to weeks. This syndrome may be idiopathic or occur in special contexts, most often involving adrenergic or serotonergic overactivity. To the best of our knowledge, reversible cerebral vasoconstriction syndrome has not previously been reported in association with Hydroxycut use in the literature. CASE PRESENTATION: We report the case of a 65-year-old Caucasian woman on longstanding citalopram who developed reversible cerebral vasoconstriction syndrome two weeks after beginning to take the weight-loss supplement Hydroxycut. CONCLUSION: There are sparse data about the safety of herbal supplements such as Hydroxycut, even though the Food and Drug Administration has banned some herbal ingredients, such as ephedra, that were in this preparation in the past. This case highlights the importance of considering herbal supplements and potential drug interactions in the genesis of otherwise unexplained reversible cerebral vasoconstriction syndrome. PMID- 22074636 TI - Staphylococcus simulans osteitis in a diabetic patient. AB - Staphylococcus simulans was identified as the aetiological agent of osteitis in a diabetic woman. Its identifying characteristics and antibiogram were confirmed. Diabetic foot frequently becomes infected and the spread of infection to bone is a major causal factor behind lower-limb amputation. Early diagnosis and appropriate treatment are essential in such cases. PMID- 22074637 TI - Cellular uptake mediated off/on responsive near-infrared fluorescent nanoparticles. AB - Fluorescence imaging, utilizing molecular fluorophores, often acts as a central tool for the investigation of fundamental biological processes and offers huge future potential for human imaging coupled to therapeutic procedures. An often encountered limitation with fluorescence imaging is the difficulty in discriminating nonspecific background fluorophore emission from a fluorophore localized at a specific region of interest. This limits imaging to individual time points at which background fluorescence has been minimized. It would be of significant advantage if the fluorescence output could be modulated from off to on in response to specific biological events as this would permit imaging of such events in real time without background interference. Here we report our approach to achieve this for the most fundamental of cellular processes, i.e. endocytosis. We describe a new near-infrared off to on fluorescence switchable nanoparticle construct that is capable of switching its fluorescence on following cellular uptake but remains switched off in extracellular environments. This permits continuous real-time imaging of the uptake process as extracellular particles are nonfluorescent. The principles behind the fluorescence off/on switch can be understood by encapsulation of particles in cellular organelles which effect a microenvironmental change establishing a fluorescence signal. PMID- 22074638 TI - Evaluation of animal and public health surveillance systems: a systematic review. AB - Disease surveillance programmes ought to be evaluated regularly to ensure they provide valuable information in an efficient manner. Evaluation of human and animal health surveillance programmes around the world is currently not standardized and therefore inconsistent. The aim of this systematic review was to review surveillance system attributes and the methods used for their assessment, together with the strengths and weaknesses of existing frameworks for evaluating surveillance in animal health, public health and allied disciplines. Information from 99 articles describing the evaluation of 101 surveillance systems was examined. A wide range of approaches for assessing 23 different system attributes was identified although most evaluations addressed only one or two attributes and comprehensive evaluations were uncommon. Surveillance objectives were often not stated in the articles reviewed and so the reasons for choosing certain attributes for assessment were not always apparent. This has the potential to introduce misleading results in surveillance evaluation. Due to the wide range of system attributes that may be assessed, methods should be explored which collapse these down into a small number of grouped characteristics by focusing on the relationships between attributes and their links to the objectives of the surveillance system and the evaluation. A generic and comprehensive evaluation framework could then be developed consisting of a limited number of common attributes together with several sets of secondary attributes which could be selected depending on the disease or range of diseases under surveillance and the purpose of the surveillance. Economic evaluation should be an integral part of the surveillance evaluation process. This would provide a significant benefit to decision-makers who often need to make choices based on limited or diminishing resources. PMID- 22074639 TI - Effects of testosterone gel treatment in hypogonadal men with liver cirrhosis. AB - INTRODUCTION: Hypogonadism characterized by low serum testosterone level, loss of libido, small testes, impotence and gynecomastia is a common clinical situation in male patients with advanced chronic liver disease. The aim of the study was to assess the efficacy and safety of testosterone replacement on muscle strength, bone mineral density (BMD), body composition and gynecomastia in hypogonadal men with liver cirrhosis. METHODS: Sixteen hypogonadal male cirrhotic patients were included and twelve completed the study. Abdominal USG and/or MRI were performed to exclude hepatocellular cancer. Testogel 50mg/day was administered for 6 months. Liver enzymes, hormone profiles and muscle strength were evaluated monthly. Body composition parameters, BMD and gynecomastia were evaluated before and after 6 months. RESULTS: Serum free testosterone level was higher (20.13 +/- 10.06 pmol/L; 57.26 +/- 39.56 pmol/L, P=0.002) after treatment. Testosterone replacement resulted in an increase in muscle strength (34.03 +/- 7.24 kg; 39.18 +/- 5.99 kg, P<0.001), the subscapular site subcutaneous fat tissue (P=0.012) and the sum of the four regions (P=0.04). Subareolar breast tissue was lower (28.83 +/- 17.18 mm; 15.00 +/- 6.74 mm, P=0.007) after treatment. No significant adverse effects were detected. DISCUSSION: Testosterone gel 50mg/day raises free testosterone to values below supraphysiological levels in cirrhotic men. Transdermal testosterone replacement improves muscle strength, ameliorates gynecomastia, alters body fat distribution and causes upper body adiposity in hypogonadal men with cirrhosis. Application of testosterone gel, which undergoes no hepatic first-pass metabolism, seems as a safe and well-tolerated agent in liver cirrhosis as compared to other anabolic steroids, which may be associated with various adverse events. PMID- 22074640 TI - Evaluations of capsule endoscopy software in reducing the reading time and the rate of false negatives by inexperienced endoscopists. AB - BACKGROUND AND OBJECTIVE: Capsule endoscopy (CE) is a comfortable for the patients; however, CE review is time-consuming. The aim of this study was (1) to evaluate the effectiveness of the CE software in reducing the CE reading time and the number of false negatives by beginners, and (2) to determine the learning curve for reading CE images. METHODS: Capsule endoscopic images were captured by Pillcam SB (Given Imaging Ltd, Tokyo, Japan), and analyzed using the proprietary RAPID 5 software. Comparison of CE reading using different software modes: manual mode, automatic mode, and QuickView (QV) mode. Three trainee endoscopists participated as CE readers. Each participant watched CE videos in which positive findings had been predefined by trained endoscopists. Each participant read the same CE record by using one of three different software modes. These were blinded on clinical history of patients. CE reading time was recorded, and the number of false negatives was counted. Each trainee endoscopist read a total of 45 CE videos, in five steps divided into nine videos per step. RESULTS: There was no significant reader associated difference between the results for the different modes. The QV software did miss some positive findings. Therefore, the total number of instances of FN by the software plus the reader in the QV mode was significantly higher than the others. The reading times in the automatic mode and the QV mode were significantly shorter than that in the manual mode. After the second step, the number of instances of false negatives significantly decreased. CONCLUSIONS: CE software is useful for reducing the reading time. Experience of approximately 20 CE readings can be considered as the first step to becoming an expert. PMID- 22074641 TI - Intramural perforation with hematoma of the esophagus. PMID- 22074642 TI - Small bowel parasitosis. PMID- 22074643 TI - Mucinous cystadenoma of the mesocolon, a rare entity frequently presenting with features of malignity: two case reports and review of the literature. AB - PURPOSE: Mucinous cystadenomas are tumors arising mostly from the ovaries and pancreas. They can also arise from the kidneys, lungs, liver and appendix, but are rarely seen in the mesocolon. Recently, they have been included in an updated classification of mesenteric cysts and cystic tumors. The WHO classification (ICD 10) divides them into three subcategories according to their malignant behavior. METHODS: This report of two cases of mucinous cystadenoma of the mesocolon discusses the diagnostic and therapeutic modalities as well as the pathophysiological pathway(s) of development of these neoplasms. RESULTS AND CONCLUSION: The diagnosis of mucinous cystadenomas of the mesocolon is challenging due to the absence of specific clinical, biological and radiological features, and is often made during or after laparotomy. Preoperative biopsy is not useful and may even lead to misdiagnosis or peritoneal spillage. Surgery is the only curative treatment, but the modalities of resection are still a subject of debate. PMID- 22074644 TI - Alterations in the emotional and memory behavioral phenotypes of transient receptor potential vanilloid type 1-deficient mice are mediated by changes in expression of 5-HT1A, GABA(A), and NMDA receptors. AB - The transient receptor potential vanilloid type 1 channel (TRPV1) receptors are expressed in various regions of the brain. Much less is known about whether TRPV1 receptors affect higher brain functions. In the present study, we demonstrated that TRPV1-knockout (TRPV1KO) mice showed antidepressant-like behaviors in a novelty-suppressed feeding test and forced swim test when compared to wild-type (WT) mice. Additionally, TRPV1KO mice exhibited increased aggressiveness and reduced social interactions in a social dominance test and social interaction test. TRPV1KO mice showed reduced short-term memory and normal long-term memory in a novel object recognition test and passive avoidance test versus WT mice. Based on these behavioral data, we investigated changes in specific receptors related to depression, anxiety, and memory in the brains of TRPV1KO and WT mice. Binding of [(3)H]-8-OH-DPAT was significantly higher in the frontal associated cortex (FrA), nucleus accumbens (NAc), and the cingulate cortex (CC) of TRPV1KO mice than WT mice, while the expression of 5-HT(1A) receptors was higher in the FrA, NAc, and cortex of TRPV1KO mice than WT mice. [(3)H]-flunitrazepam binding was also significantly higher in the FrA, striatum (CPU), and the CC of TRPV1KO versus WT mice. In contrast, [(3)H]-musicmol binding in the FrA, CPU, NAc, CC, and the dentate gyrus (DG) was significantly lower in TRPV1KO mice than WT mice. The expression of GABA(A)gamma(2) was higher in the NAc, CPU, and cortex of TRPV1KO versus WT mice, whereas the expression of GABA(A)alpha(2) was lower in the FrA, CPU, NAc, and cortex in TRPV1KO mice than WT mice. Finally, [(3)H]-MK 801 binding was decreased in the CPU and CA1 of TRPV1KO versus WT mice. The expression of NR2A was lower in the hippocampus of TRPV1KO versus WT mice. These data suggest that the loss of TRPV1 results in antidepressant-like, anxiolytic, abnormal social and reduced memorial behaviors due to changes in expression of 5 HT(1A), GABA(A,) and NMDA receptors. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22074645 TI - Alpha-cobratoxin inhibits T-type calcium currents through muscarinic M4 receptor and Gomicron-protein betagamma subunits-dependent protein kinase A pathway in dorsal root ganglion neurons. AB - The long-chain neurotoxic protein, alpha-cobratoxin (alpha-CTx), has been shown to have analgesic effects. However, the underlying mechanisms still remain unclear. In this study, we examined the effects of alpha-CTx on T-type calcium channel currents (T-currents) and elucidated the relevant mechanisms in mouse dorsal root ganglion (DRG) neurons. Our results showed that alpha-CTx reversibly inhibited T-currents in a dose-dependent manner. This inhibitory effect was blocked by the selective muscarinic M4 receptor antagonist tropicamide, while methyllycaconitine, a specific antagonist for the alpha7 subtype of nicotinic receptor had no effect. siRNA targeting the M4 receptor in small DRG neurons abolished alpha-CTx-induced T-current inhibition. Intracellular application of GDP-beta-S or a selective antibody against the G(o)alpha-protein, as well as pretreatment of the cells with pertussis toxin, abolished the inhibitory effects of alpha-CTx. The M4 receptor-mediated response was blocked by dialyzing cells with QEHA peptide or anti-G(beta) antibody. Pretreatment of the cells with protein kinase A (PKA) inhibitor H89 or intracellular application of PKI 6-22 abolished alpha-CTx-induced T-current inhibition in small DRG neurons, whereas inhibition of phosphatidylinositol 3-kinase or PKC elicited no such effects. In addition, alpha-CTx significantly increased PKA activity in DRG neurons, whereas pretreatment of the cells with tropicamide abolished this effect. In summary, our results suggest that activation of muscarinic M4 receptor by alpha-CTx inhibits T currents via the G(betagamma) of G(o)-protein and PKA-dependent pathway. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22074646 TI - Preparation and characterization of imprinted monolith with metal ion as pivot. AB - This report provided the first example of using pivot concept to prepare monolithic molecularly imprinted polymers (MIPs) with ketoprofen (KET) imprints, in which metal ions were employed as mediator between the functional monomer and the template to achieve higher fidelity of imprint. To solve metal ions in pre polymerization system, a new ternary porogen of dimethyl sulfoxide-toluene isooctane was developed for preparation of MIP monoliths with high porosity and good permeability. The effect of polymerization parameters such as the nature of metal ions, the ratio of template to metal ion and the degree of crosslinking, on the permeability, morphology and affinity of the metal ion mediated MIP monolith were studied. The experiments demonstrated that Ni(2+), Co(2+) and Zn(2+) can be applied as pivot to prepare KET-imprinted monolith. Relative to monolithic MIP without metal ions, all the ion-mediated macropore MIP monoliths showed enhanced permeability, capacity factor and selectivity factor. High permeability (1.06*10( 7)mm(2)) was obtained on the Co(2+)-mediated MIP monolith and great selectivity factor (3.84) was achieved on the Ni(2+)-mediated one. The stoichiometric displacement model was constructed to investigate the recognition mechanism of metal-ion mediated MIP. The results indicate that metal ion as pivot not only improves the affinity but also allows the fine-tuning on the macroporous structure of MIP monolith. PMID- 22074647 TI - Determination of bromate in sea water using multi-dimensional matrix-elimination ion chromatography. AB - A multi-dimensional matrix-elimination ion chromatography approach has been applied to the determination of bromate in seawater samples. Two-dimensional and three-dimensional configurations were evaluated for their efficacy to eliminate the interference caused by the high concentration of ubiquitous ions present in seawater, such as chloride and sulfate. A two-dimensional approach utilising a high capacity second dimension separation comprising two Dionex AS24 columns connected in series was applied successfully and permitted the determination of bromate in undiluted seawater samples injected directly onto the ion chromatography system. Using this approach the limit of detection (LOD) for bromate based on a signal to noise ratio of 3 was 1050 MUg/L using a 500 MUL injection loop. Good linearity was obtained for bromate with correlation coefficients for the calibration curves of 0.9981 and 0.9996 based on peak height and area, respectively. A three-dimensional method utilising two 10-port switching valves to allow sharing of the second suppressor and detector between the second and third dimension separations showed better resolution and detection for bromate and reduced the LOD to 60 MUg/L for spiked seawater samples. Good linearity was maintained with correlation coefficients of 0.9991 for both peak height and area. Ozonated seawater samples were also analysed and exhibited a non linear increase in bromate level on increasing ozonation time. A bromate concentration in excess of 1770 MUg/L was observed following ozonation of the seawater sample for 120 min. Recoveries for the three-dimensional system were 92% and 89% based on peak height and area, respectively, taken over 5 ozonated samples with 3 replicates per sample. PMID- 22074648 TI - Mathematical model using non-uniform flow distribution for dynamic protein breakthrough with membrane adsorption media. AB - A mathematical model has been investigated to predict protein breakthrough during membrane adsorption/chromatography operations. The new model incorporates a non uniform boundary condition at the column inlet to help describe the deviation from plug flow within real membrane adsorption devices. The model provides estimated breakthrough profiles of a binding protein while explicitly accounting for non-uniform flow at the inlet of the separation operation by modeling the flow distribution by a polynomial. We have explored experimental breakthrough curves produced using commercial membrane adsorption devices, as well as novel adsorption media of nanolayered nanofiber membranes, and compare them to model predictions. Further, the impact of using various simplifying assumptions is considered, which can have a dramatic effect on the accuracy and predictive ability of the proposed models. The new model, using only simple batch equilibrium and kinetic uptake rate data, along with membrane properties, is able to accurately predict the non-uniform and unsymmetrical shape for protein breakthrough during operation of membrane adsorption/chromatography devices. PMID- 22074649 TI - Simultaneous determination of 23 amino acids and 7 biogenic amines in fermented food samples by liquid chromatography/quadrupole time-of-flight mass spectrometry. AB - A novel liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOFMS) method was developed for the simultaneous determination of 23 amino acids and 7 biogenic amines in food samples. These analytes were pre column derivatized with dansyl chloride and then separated in an Acquity column (1.7 MUm; 2.1 mm * 100 mm). The separation of 31 compounds including an internal standard was achieved within 25 min at a flow rate of 0.2 mL/min. The method linearity for each amino acid and biogenic amine had a relatively wide range with r(2)>0.99. The intra- and inter-day precision, expressed as relative standard deviation (RSD), ranged from 1.1 to 4.6% and from 2.0 to 11.2%, respectively. The limit of detection was between 0.005 and 0.4 MUg/mL. With a simple dilution, recoveries of around 80-120% were obtained for most of the compounds. No significant matrix effect was observed, and the developed method was successfully applied to the analysis of amino acids and biogenic amines in beer, cheese and sausage samples. PMID- 22074650 TI - Hope for the future. PMID- 22074651 TI - Continuum of care in the emergency department. PMID- 22074652 TI - Factors influencing patient assignment to level 2 and level 3 within the 5-level ESI triage system. AB - INTRODUCTION: Prospectively assessing factors that influence triage nurse assignment of patients to the higher risk level 2 compared to the lower risk level 3 has not previously been explored within the 5-level Emergency Severity Index (ESI) triage system. Considering the large amount of information available about the patient, less experienced triage nurses often struggle in deciding what patient information is truly relevant when assessing if a high-risk situation exists. The primary aim of this study was to identify specific factors used by triage nurses to differentiate level 2 patients from level 3 patients. METHODS: A convenience sample of triage nurses was recruited from 2 ED sites. If at the completion of the nurse-patient triage interaction the nurse assigned the patient to either level 2 or level 3, the triage nurse then completed a questionnaire related to factors that influenced patient assignment. RESULTS: Overall, 18 triage nurses participated in the study with a total of 334 nurse-patient triage interactions collected. Patient age, vital signs, and need for a timely intervention were found to be significant factors that influenced patient assignment to level 2 while expected number of resources influenced patient assignment to level 3. DISCUSSION: Utilizing experienced triage nurses on average, this study identified specific, objective factors that, combined with factors already delineated in the ESI Version 4 Implementation Manual, have useful implications for less experienced triage nurses by providing a more comprehensive and relevant foundation for data gathering and decision making. PMID- 22074653 TI - Transforming an emergency department: from crisis to excellence. PMID- 22074654 TI - A 29-year-old man with dizziness and headache after skydiving. PMID- 22074655 TI - Experience talks. PMID- 22074656 TI - Syndromes of "holiday heart". PMID- 22074657 TI - New and emerging agents for the treatment of castration-resistant prostate cancer. AB - Most men with recurrent prostate cancer (CaP) initially respond to androgen deprivation therapy but eventually develop metastatic castration-resistant prostate cancer (CRPC). Over the last decade, new therapeutic targets have been identified in CRPC and several new drugs have reached advanced stages of clinical development. In 2010, the Food and Drug Administration (FDA) approved sipuleucel T and cabazitaxel, and in 2011, abiraterone for patients with metastatic CRPC based on phase 3 trials showing improved survival. Although not yet available for clinical use, a press release in June 2011 announced that radium 223 also demonstrated a survival advantage in men with metastatic CRPC. Emerging therapies in advanced stages of clinical development in CRPC include the hormonal therapies MDV3100 and TAK 700, and the immunotherapy ipilimumab. Results are also pending on phase 3 studies comparing docetaxel plus prednisone with docetaxel given with the novel agents aflibercept, dasatinib, lenalidomide, and custirsen. In addition to these new and emerging therapeutic agents, denosumab was approved for the prevention of skeletal complications in patients with bone metastases due to solid tumor malignancies, providing an alternative to zoledronic acid. While the addition of these new treatment options is a great advance for men with metastatic CRPC, there are many new questions arising regarding sequencing of these treatments with each other, with previously existing therapies, and with the emerging agents now in clinical trials. Furthermore, there are concerns that on-going phase 3 trials may be contaminated if patients go off study treatment to start 1 of the newly approved agents or take the agent subsequently. These realities make clinical trial design more challenging than ever. PMID- 22074659 TI - [Solution to case 36. Giant diverticulum of the sigmoid colon]. PMID- 22074660 TI - Chromatin remodelling protein SMAR1 inhibits p53 dependent transactivation by regulating acetyl transferase p300. AB - Acetylation of p53 is indispensable for its transcriptional activities and induction of apoptosis upon DNA damage. Here, we show that chromatin remodelling protein SMAR1 inhibits p53 acetylation and p53 dependent apoptosis by repressing p300 expression in response to DNA damage. The repression of p300 expression by SMAR1 is relieved upon treatment with proteosomal inhibitors MG132 and Lactacystin. We demonstrate that SMAR1 interacts with p53-p300 transcriptional complex and SMAR1 overexpression antagonizes p300 interaction with p53 and suppresses activation of p53 apoptotic targets and p53 regulated miRNA miR-34a. Conversely, knockdown of SMAR1 promotes p300 accumulation and p53 acetylation while ectopic expression of p300 rescues SMAR1 inhibition on p53. Collectively, these results indicate that SMAR1 is an important player in p300-p53 regulated DNA damage signalling pathway and can exert its effect on apoptosis in a transcription independent manner. PMID- 22074661 TI - Comparative proteomic analysis to dissect differences in signal transduction in activating TSH receptor mutations in the thyroid. AB - In the thyroid, cAMP controls both thyroid growth and function. Gain-of-function mutations in the thyroid-stimulating hormone receptor (TSHR) lead to constitutive cAMP formation and are a major cause of autonomous thyroid adenomas. The impact of activating TSHR mutations on the signal transduction network of the thyrocyte is not fully understood. To gain more insights into constitutive TSHR signaling, rat thyrocytes (FRTL-5 cells) with stable expression of three activating TSHR mutants (mutTSHR: A623I, L629F and Del613-621), which differ in their functional characteristics in vitro, were analyzed by a quantitative proteomic approach and compared to the wild-type TSHR (WT-TSHR). This study revealed (1) differences in the expression of Rab proteins suggesting an increased TSHR internalization in mutTSHR but not in the WT-TSHR; (2) differential stimulation of PI3K/Akt signaling in mutTSHR vs. WT-TSHR cells, (3) activation of Epac, impairing short time Akt phosphorylation in both, mutTSHR and WT-TSHR cells. Based on the analysis of global changes in protein expression patterns, our findings underline the complexity of gain-of-function TSHR signaling in thyrocytes, which extends beyond pure cAMP and/or IP formation. Moreover, evidence for augmented endocytosis in the mutTSHR, adds to a new concept of TSHR signaling in thyroid autonomy. Further studies are required to clarify whether the observed differences in Rab, PI3K and Epac signaling may contribute to differences in the phenotypic presentation, i.e. stimulation of function and growth of thyroid autonomy in vivo. PMID- 22074662 TI - Pigment epithelium-derived factor reduces the PDGF-induced migration and proliferation of human aortic smooth muscle cells through PPARgamma activation. AB - Our previous study demonstrated that pigment epithelium-derived factor (PEDF) plays an important role in the proliferation and migration of human aortic smooth muscle cells (HASMCs). In the present study, we examined whether PEDF inhibited platelet-derived growth factor (PDGF)-stimulated HASMC migration and proliferation. PEDF dose-dependently reduced PDGF-induced HASMC migration and proliferation in vitro and also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21(Cip1) and increased expression of the cyclin-dependent kinase inhibitor p27(Kip1). The antiproliferative and antimigratory effects of PEDF were partially blocked by the PPARgamma antagonist GW9662, but not by the PPARalpha antagonist MK886. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice injected intravenously with PEDF or vehicle. After 2 weeks, both the neointima/media area ratio and cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima were significantly reduced and again these effects were partially reversed by GW9662 pretreatment. Our data show that PEDF increases PPARgamma activation, preventing entry of HASMCs into the cell cycle in vitro and reducing the neointimal area and cell proliferation in the neointima in vivo. Thus, PEDF may represent a safe and effective novel target for the prevention and treatment of vascular proliferative diseases. PMID- 22074664 TI - Polyethylene glycol-conjugated hyaluronic acid-ceramide self-assembled nanoparticles for targeted delivery of doxorubicin. AB - Polyethylene glycol (PEG)-conjugated hyaluronic acid-ceramide (HACE) was synthesized for the preparation of doxorubicin (DOX)-loaded HACE-PEG-based nanoparticles, 160 nm in mean diameter with a negative surface charge. Greater uptake of DOX from these HACE-PEG-based nanoparticles was observed in the CD44 receptor highly expressed SCC7 cell line, compared to results from the CD44 negative cell line, NIH3T3. A strong fluorescent signal was detected in the tumor region upon intravenous injection of cyanine 5.5-labeled nanoparticles into the SCC7 tumor xenograft mice; the extended circulation time of the HACE-PEG-based nanoparticle was also observed. Pharmacokinetic study in rats showed a 73.0% reduction of the in vivo clearance of DOX compared to the control group. The antitumor efficacy of the DOX-loaded HACE-PEG-based nanoparticles was also verified in a tumor xenograft mouse model. DOX was efficiently delivered to the tumor site by active targeting via HA and CD44 receptor interaction and by passive targeting due to its small mean diameter (<200 nm). Moreover, PEGylation resulted in prolonged nanoparticle circulation and reduced DOX clearance rate in an in vivo model. These results therefore indicate that PEGylated HACE nanoparticles represent a promising anticancer drug delivery system for cancer diagnosis and therapy. PMID- 22074663 TI - The therapeutic efficacy of camptothecin-encapsulated supramolecular nanoparticles. AB - Nanomaterials have been increasingly employed as drug(s)-incorporated vectors for drug delivery due to their potential of maximizing therapeutic efficacy while minimizing systemic side effects. However, there have been two main challenges for these vectors: (i) the existing synthetic approaches are cumbersome and incapable of achieving precise control of their structural properties, which will affect their biodistribution and therapeutic efficacies, and (ii) lack of an early checkpoint to quickly predict which drug(s)-incorporated vectors exhibit optimal therapeutic outcomes. In this work, we utilized a new rational developmental approach to rapidly screen nanoparticle (NP)-based cancer therapeutic agents containing a built-in companion diagnostic utility for optimal therapeutic efficacy. The approach leverages the advantages of a self-assembly synthetic method for preparation of two different sizes of drug-incorporated supramolecular nanoparticles (SNPs), and a positron emission tomography (PET) imaging-based biodistribution study to quickly evaluate the accumulation of SNPs at a tumor site in vivo and select the favorable SNPs for in vivo therapeutic study. Finally, the enhanced in vivo anti-tumor efficacy of the selected SNPs was validated by tumor reduction/inhibition studies. We foresee our rational developmental approach providing a general strategy in the search of optimal therapeutic agents among the diversity of NP-based therapeutic agents. PMID- 22074665 TI - Three-dimensional paper-based electrochemiluminescence immunodevice for multiplexed measurement of biomarkers and point-of-care testing. AB - In this work, electrochemiluminescence (ECL) immunoassay was introduced into the recently proposed microfluidic paper-based analytical device (MUPADs) based on directly screen-printed electrodes on paper for the very first time. The screen printed paper-electrodes will be more important for further development of this paper-based ECL device in simple, low-cost and disposable application than commercialized ones. To further perform high-performance, high-throughput, simple and inexpensive ECL immunoassay on MUPAD for point-of-care testing, a wax patterned three-dimensional (3D) paper-based ECL device was demonstrated for the very first time. In this 3D paper-based ECL device, eight carbon working electrodes including their conductive pads were screen-printed on a piece of square paper and shared the same Ag/AgCl reference and carbon counter electrodes on another piece of square paper after stacking. Using typical tris-(bipyridine) ruthenium (II) - tri-n-propylamine ECL system, the application test of this 3D paper-based ECL device was performed through the diagnosis of four tumor markers in real clinical serum samples. With the aid of a facile device-holder and a section-switch assembled on the analyzer, eight working electrodes were sequentially placed into the circuit to trigger the ECL reaction in the sweeping range from 0.5 to 1.1 V at room temperature. In addition, this 3D paper-based ECL device can be easily integrated and combined with the recently emerging paper electronics to further develop simple, sensitive, low-cost, disposable and portable MUPAD for point-of-care testing, public health and environmental monitoring in remote regions, developing or developed countries. PMID- 22074666 TI - Strong light-induced reorganization of pigment-protein complexes of thylakoid membranes in rye (spectroscopic study). AB - The supramolecular reorganization of LHCII complexes within the thylakoid membrane in Secale cereale leaves under low and high light condition was examined. Rye seedlings were germinated hydroponically in a climate chamber with a 16 h daylight photoperiod, photosynthetic photon flux density (PPFD) of 150 MUmo lm(-2)s(-1) and 24/16 degrees C day/night temperature. The influence of pre illumination of the plants with high light intensity on the PSII antenna complexes was studied by comparison of the structure and function of the LHCII complexes and organization of thylakoid membranes isolated from 10-day-old plants illuminated with low (150 MUmo lm(-2)s(-1)) or high (1200 MUmo lm(-2)s(-1)) light intensity. Aggregated and trimeric with monomeric forms of LHCII complexes were separated from the whole thylakoid membranes using non-denaturing electrophoresis. Analyses of fluorescence emission spectra of these different LHCII forms showed that the monomer was the most effective aggregating antenna form. Moreover, photoprotection connected with LHCII aggregation was more effective upon LHCII monomers in comparison to trimer aggregation. Light stress induced specific organization of neighboring LHCII complexes, causing an increase in fluorescence yield of the long-wavelength bands (centered at 701 and 734 nm). The changes in the organization of the thylakoid membrane under light stress, observed by analysis of absorbance spectra obtained by Fourier transform infrared spectroscopy, also indicated light-induced LHCII aggregation. PMID- 22074667 TI - It is important to note that RWD will never replace the more traditional and more robust RCT data; however, the emerging trend is to incorporate data that are more generalizable. Introduction. AB - BACKGROUND: The Patient Protection and Affordable Care Act brought considerable attention to comparative effectiveness research (CER). OBJECTIVES: To (a) suggest best practices for conducting and reporting CER using "real-world data" (RWD), (b) describe some of the data and infrastructure requirements for conducting CER using RWD, (c) identify statistical challenges with the analysis of nonrandomized studies and suggest appropriate techniques to address those challenges, (d) recognize the value of patient-reported outcomes in CER, (e) encourage the incorporation of observational data into randomized controlled studies, and (f) highlight the importance of incorporating payers in industry sponsored research. SUMMARY: The first article in this supplement, "Something old, something new..." provides a policy perspective on the recent evolution of CER. It reviews the historical context, discusses the "promise and fear" of CER, and then describes the new role of the Patient-Centered Outcomes Research Institute (PCORI) in defining and sponsoring CER. The second paper, "Ten Commandments," proposes a series of tenets for planning, conducting, and reporting CER done with RWD. Oriented for basic-to-intermediate researchers, it combines standard scientific research principles with considerations specific to nonrandomized, RWD studies. The third article, "Infrastructure Requirements," points out that effective use of secondary data requires addressing major methodological and infrastructural issues, including development of analytical tools to readily access and analyze data, formulation of guidelines to enhance quality and transparency, establishment of data standards, and creation of data warehouses that respect the privacy and confidentiality of patients. It identifies gaps that must be filled to address the underlying issues, with emphasis on data standards, data quality assurance, data warehouses, computing environment, and protection of privacy and confidentiality. The fourth paper, "Statistical Issues," discusses how the validity of analytic results from observational studies is adversely impacted by biases that may be introduced due to lack of randomization. It reviews some of the methodological challenges that arise in the analysis of data from nonrandomized studies, with particular emphasis on the limitations of traditional approaches and potential solutions from recent methodological developments. The fifth paper, "Considerations on the Use of Patient Reported Outcomes (PROs)," describes how PRO data can play a critical role in guiding patients, health care providers, payers, and policy makers in making informed decisions regarding patient-centered treatment from among alternative options and technologies and have been noted as such by PCORI. However, collection and interpretation of such data within the context of CER have not yet been fully established. It discusses some challenges with including PROs in CER initiatives, provides a framework for their effective use, and proposes several areas for future research. Lastly, "Developing a Collaborative Study Protocol..." indicates that there is the potential, the desire, and the capability for payers to be involved in CER studies, combining elements of their own observational data with prospective studies. It describes a case example of a payer, a pharmaceutical company, and a research organization collaborating on a prospective study to examine the effect of prior authorization for pregabalin on health care costs to the payer. CONCLUSION: Researchers at Pfizer routinely conduct CER-type studies. In this supplement, we have proposed some approaches that we believe are useful in developing certain kinds of evidence and have described some of our experiences. Our experiences also make us acutely aware of the limitations of approaches and data sources that have been used for CER studies and suggest that there is a need to further develop methods that are most useful for answering CER questions. PMID- 22074668 TI - Something old, something new, something borrowed...comparative effectiveness research: a policy perspective. PMID- 22074669 TI - "Ten commandments" for conducting comparative effectiveness research using "real world data". PMID- 22074670 TI - Infrastructure requirements for secondary data sources in comparative effectiveness research. PMID- 22074671 TI - Statistical issues with the analysis of nonrandomized studies in comparative effectiveness research. PMID- 22074672 TI - Considerations on the use of patient-reported outcomes in comparative effectiveness research. PMID- 22074673 TI - Developing a collaborative study protocol for combining payer-specific data and clinical trials for CER. PMID- 22074674 TI - Low adherence to influenza vaccination campaigns: is the H1N1 virus pandemic to be blamed? AB - BACKGROUND: Over the last few months, debates about the handling of the influenza virus A (H1N1) pandemic took place, in particular regarding the change of the WHO pandemic definition, economic interests, the dramatic communication style of mass media. The activation of plans to reduce the virus diffusion resulted in an important investment of resources. Were those investments proportionate to the risk? Was the pandemic overrated? The workload of the Pediatric Emergency Room (P.E.R.) at a teaching hospital in Varese (Northern Italy) was investigated in order to evaluate the local diffusion and severity of the new H1N1 influenza epidemic. DISCUSSION: A 100% increase of the number of P.E.R. visits, particularly for influenza-like illness, was recorded during weeks 42-46 of 2009 (October, 17 to November, 2); the low rate of hospitalization and the mild presentation of the infection gave rise to the conclusion that the pandemic risk was overrated. Mass media communications concerning the new virus created a disproportionate fear in the population that significantly enhanced the burden of cares at the hospital. In the absence of generally implemented measures for etiological diagnosis, the actual incidence of the H1N1 infection could not be estimated. Virus identification, in fact, was limited to children showing severe symptoms after consultancy with an infectious disease specialist. The alarming nature of the communication campaign and the choice to limit etiologic diagnosis to severe cases created a climate of uncertainty which significantly contributed to the massive admissions to the P.E.R.. SUMMARY: The communication strategy adopted by the mass media was an important element during the pandemic: the absence of clarity contributed to the spread of a pandemic phobia that appeared to result more from the sensationalism of the campaign than from infection with the novel influenza A variant of human, avian, swine origin virus. One relevant effect of the media coverage was the extremely low adherence rate to the vaccination campaign for the 2009-2010 and 2010-2011, especially among the high risk population and health care workers. One positive consequence was, however, the spread of preventive hygiene measures, such as hand washing. PMID- 22074675 TI - Chemical structure of the O-polysaccharide isolated from Pectobacterium atrosepticum SCRI 1039. AB - The lipopolysaccharide (LPS) of the bacterium Pectobacterium atrosepticum SCRI 1039 was hydrolyzed and the products were separated. A study of the obtained O polysaccharide by means of chemical methods, GLC, GLC-MS, and NMR spectroscopy allowed us to identify a branched polymer with a pentasaccharide repeating unit of the structure shown below, in which the fucose residue was partially O acetylated at C-2, C-3 or C-4. PMID- 22074676 TI - Synthesis of a novel pentasaccharide core component from the lipooligosaccharide of Moraxella catarrhalis. AB - The novel pentasaccharide [p-(trifluoroacetamido)phenyl]ethyl 3-O-beta-D glucopyranosyl-4-O-beta-D-glucopyranosyl-6-O-[2-O-(alpha-D-glucopyranosyl)-beta-D glucopyranosyl]-alpha-D-glucopyranoside (1), which includes a linker moiety to enable facile coupling to an antigenic protein, was synthesised as a component of a potential vaccine candidate against the Gram-negative bacterium Moraxella catarrhalis. This microorganism is one of three principal causative agents of otitis media in children. The pentasaccharide represents a common cross-serotype (A, B and C) structure from the lipooligosaccharides of Moraxella catarrhalis. PMID- 22074677 TI - Reversible opacification of a hydrophilic acrylic intraocular lens. AB - A 56-year-old woman with diabetic retinopathy and chronic myelogenous leukemia had phacoemulsification cataract removal and hydrophilic acrylic intraocular lens (IOL) (Akreos MI-60) implantation in both eyes. One month after surgery, significant IOL opacity and severe cystoid macular edema were observed in both eyes. After bilateral intravitreal injection of bevacizumab (Avastin) to control macular edema, central clearing of the IOL opacity was observed in both eyes. Two months after the injection, the IOL opacity had almost disappeared from both eyes. To our knowledge, this is the first case of early postoperative bilateral IOL opacity in a hydrophilic acrylic IOL cleared after anti-vascular endothelial growth factor (VEGF) intravitreal injection. The role of anti-VEGF therapy in clearing IOL opacification requires further investigation. PMID- 22074678 TI - Measurement of tooth and implant mobility under physiological loading conditions. AB - In vivo measurement of the mobility of teeth under physiological loading has been subject of research for years. Comparing the deflection under load of dental implants with teeth provides valuable input for designing restorations spanning both teeth and implants. Physiological force rise time of about 50-100 ms and displacement of 10-100 MUm requires high spatial and temporal resolution of the measurement set-up. Using an optical system attached to the teeth/implants to be measured and a light source attached to a point of reference, displacement of teeth and implants under axial and lateral loading was measured on a series of volunteers. Axial displacement of teeth shows strong time dependence consistent with (hydraulic) damping not observed for lateral loads. Displacement under lateral loading was found to be about one order of magnitude higher than under axial load. For dental implants elastic deflection was observed in axial and lateral direction without measurable influence of the load rise time. For purely axial loading, dental implants and teeth show similar deflection under physiological force rise time but for lateral loading the considerably difference between teeth and implant may put some restrictions on the construction of tooth implant-bridges, especially for teeth in the anterior region. PMID- 22074679 TI - Distinct effects of NPY13-36, a specific NPY Y2 agonist, in a model of rodent endotoxemia on leukocyte subsets and cytokine levels. AB - Even now, sepsis remains a major problem in modern clinical medicine, leading to systemic inflammatory response including altered leukocyte subset distribution and increased cytokine release. As immune cells are known to express NPY receptors, we investigated the effects of a specific NPY Y(2) receptor agonist (NPY(13-36)) and/or the corresponding Y(2) receptor antagonist BIIE0246 treatment on blood (by FACS analyses) and tissue (by immunohistochemistry) leukocyte subsets as well as on levels of IL-4, IL-6, IL-10, TNF-alpha, INF-gamma (by Cytometric Bead Array) in healthy and acutely endotoxemic rats. Results show a significant decrease in blood monocytes after LPS challenge in endotoxemic control animals (by 93%), in endotoxemic NPY(13-36) treated animals (by 83%) and in endotoxemic BIIE0246 treated animals (by 88%) as compared to the corresponding healthy controls. Endotoxemic control animals showed a significant increase of TNF-alpha (by 98%) as compared to the healthy control group. A treatment with NPY(13-36) significantly stabilized TNF-alpha level in endotoxemic animals. This study indicates distinct subset- and cytokine-specific in vivo effects induced by an NPY Y(2) receptor specific treatment after a short-term LPS challenge. PMID- 22074680 TI - Malignant fibrous histiocytoma of the urinary bladder as a post-radiation secondary cancer: a case report. AB - INTRODUCTION: Malignant fibrous histiocytomas have been periodically reported as the primary tumor in various organs including the urinary bladder, and is the second most frequent sarcoma of the urinary tract in adults. This report discusses a case of the well established diagnosis of a malignant fibrous histiocytoma of the bladder occurring as a post-radiation cancer after the treatment of a cervical carcinoma. Our findings support those of many previous studies and make the view of the nature of the disease clearer. CASE PRESENTATION: We report the case of a 54-year-old Thai woman who had been treated with radiation therapy for cervical cancer, who presented to our facility with urinary incontinence. Initially, our patient was diagnosed as having a high-grade urothelial carcinoma. Subsequent radical surgery rendered the final pathological diagnosis, confirmed histologically and immunohistochemically as malignant fibrous histiocytoma, with clinical and pathological staging of T4b N0 M0. Adjuvant chemotherapy was provided for our patient. CONCLUSIONS: This type of malignancy is very aggressive and easily misdiagnosed due to its rarity. Therefore, in a patient with a prior history of irradiation in the pelvic area, this should be considered as a differential diagnosis to ensure early correct diagnosis and treatment. PMID- 22074681 TI - Solvent effects in the excited-state tautomerization of 7-azaindole: a theoretical study. AB - The solvent effect often changes the mechanism of a chemical reaction. Experimental studies of the excited-state tautomerization of 7-azaindole (7AI) suggested that the intrinsic reactions occur via the concerted triple and double proton transfer mechanisms in the gas and liquid phases, respectively. Theoretical study is required to understand how the solvent effect changes the mechanism; however, such studies have rarely been performed in the excited-state. In this study, systematic quantum mechanical calculations were performed to study the excited-state tautomerization of 7AI in methanol. Electronic structures and energies for the reactant, transition state, and product were computed at the complete active space self-consistent field levels with the second-order multireference perturbation theory (MRPT2) to consider the dynamic electron correlation. The IEFPCM and SM8 methods were used to include solvent effect in the excited and ground-state calculations, respectively. The excited-state double proton transfer (ESDPT) in 7AI-CH(3)OH and the triple proton transfer (ESTPT) in 7AI-(CH(3)OH)(2) both occur via a concerted but asynchronous mechanism. The ESTPT barrier was smaller than the activation energy of solvent reorganization; however, the amount of 7AI-(CH(3)OH)(2) in methanol is very small because the complex formation is entropically very unfavorable. Therefore, the ESTPT is not an important path. The MRPT2 barrier of ESDPT was 2.8 kcal/mol, which agrees very well with the experimental value. The MRPT2 barrier of deuterium (D) transfer is larger than the activation energy of solvent reorganization; therefore, the intrinsic D transfer is rate-limiting, while the proton transfer must compete with solvent reorganization. The time-dependent density functional theory (TDDFT) was also used for comparison. Most TDDFT methods used in this study failed to predict transition state structures or barriers of the excited-state tautomerization. Additionally, the TDDFT levels failed to predict correct dipole moments in the excited-state, which produced an unreliable solvent effect on barrier heights. PMID- 22074683 TI - The new classification criteria for rheumatoid arthritis and their impact on therapeutic decisions. PMID- 22074684 TI - Measles antibodies and response to vaccination in children aged less than 14 months: implications for age of vaccination. AB - Passive immunity against measles decreases during the first months of life. The objective of this study was to determine titres of measles antibodies in children aged 9-14 months and their mothers before vaccination, and the children's response to vaccination. Blood samples were collected by capillary puncture before and 28 days after vaccination. Samples were obtained between February and June 2007 during an ongoing measles outbreak. Titres of specific measles IgG antibodies were determined by enzyme-linked immunosorbent assay. Seroconversion was defined as the presence of antibodies after vaccination in subjects without antibodies before vaccination. Maternal antibodies were present in 37.7% of all 69 children included and in 45.1% of children aged 9 months. Of the 51 children in whom a second sample was obtained, 31 (60.8%) were seronegative before vaccination and 61.3% seroconverted. Interference of maternal antibodies was 30%. Advancing the first dose of measles vaccination from 15 to 12 months is a correct strategy, given the increase in the time of susceptibility of infants to measles. PMID- 22074685 TI - Identification of bacterial microflora in the midgut of the larvae and adult of wild caught Anopheles stephensi: a step toward finding suitable paratransgenesis candidates. AB - To describe the midgut microbial diversity and to find the candidate bacteria for the genetic manipulation for the generation of paratransgenic Anopheline mosquitoes refractory to transmission of malaria, the microbiota of wild larvae and adult Anopheles stephensi mosquito midgut from southern Iran was studied using a conventional cell-free culture technique and analysis of a 16S ribosomal RNA (rRNA) gene sequence library. Forty species in 12 genera including seven Gram negative Myroides, Chryseobacterium, Aeromonas, Pseudomonas, Klebsiella, Enterobacter and Shewanella and five Gram-positive Exiguobacterium, Enterococcus, Kocuria, Microbacterium and Rhodococcus bacteria were identified in the microbiota of the larvae midgut. Analysis of the adult midgut microbiota revealed presence of 25 Gram-negative species in five genera including Pseudomonas, Alcaligenes, Bordetella, Myroides and Aeromonas. Pseudomonas and Exiguobacterium with a frequency of 51% and 14% at the larval stage and Pseudomonas and Aeromonas with a frequency of 54% and 20% at the adult stage were the most common midgut symbionts. Pseudomonas, Aeromonas and Myroides genera have been isolated from both larvae and adult stages indicating possible trans-stadial transmission from larva to adult stage. Fast growth in cheap media, Gram negative, and being dominantly found in both larvae and adult stages, and presence in other malaria vectors makes Pseudomonas as a proper candidate for paratransgenesis of An. stephensi and other malaria vectors. PMID- 22074686 TI - Monoclonal antibody 12D5 inhibits eosinophil infiltration in the brain of Angiostrongylus cantonensis-infected BALB/c mice. AB - Each of BALB/c mice was infected with 50 Angiostrongylus cantonensis larvae. One group of mice received an intraperitoneal injection of 50 MUg 12D5 monoclonal antibody (mAb) against a 98 kDa antigen of adult worms at 10 days post-infection (dpi), with a booster injection of 25 MUg at 12 dpi. Five mice from each group were sacrificed at 14 dpi for pathological examination and RNA extraction. The infiltration of eosinophils and severity of eosinophilic meningitis were reduced in 12D5 mAb-treated mice compared with the infected mice without 12D5 treatment. The levels of eotaxin mRNA expression in spleen significantly increased and the expression of the Th2-type cytokine IL-5 significantly decreased. However, the expression of IL-4 was not changed. 12D5 mAb can observably enhance the survival rate of infected mice and reduce symptoms of angiostrongyliasis. A. cantonensis infection is a major cause of eosinophilic meningoencephalitis. The results of this study could be helpful for the development of treatment of human angiostrongylosis. PMID- 22074688 TI - Development and analytical validation of an enzyme-linked immunosorbent assay (ELISA) for the measurement of alpha(1)-proteinase inhibitor in serum and faeces from cats. AB - The objective of this study was to develop and analytically validate an ELISA for the measurement of alpha(1)-proteinase inhibitor (alpha(1)-PI) in serum and faeces from cats. Lower detection limit, linearity, accuracy, precision, reproducibility, and reference intervals were determined. The lower detection limits were 0.02 g/L for serum and 0.04 MUg/g for faeces. The observed-to expected (O/E) ratios for serial dilutions of serum and faecal samples ranged from 100.0 to 129.7% (mean+/-SD: 112.2+/-9.9%) and 103.5 to 141.6% (115.6+/ 12.8%), respectively. The O/E ratios for samples spiked with seven known concentrations of alpha(1)-PI ranged from 82.3 to 107.8% (94.7+/-7.6%) for serum, and 78.5 to 148.7% (96.8+/-18.2%) for faeces. The coefficients of variation for intra-assay and inter-assay variability were <7.9% and <12.1% for serum, and 5.3%, 11.8%, 14.2%, and 7.7%, 10.2%, 20.4% for faeces, respectively. Reference intervals were 0.6-1.4 g/L for serum and upto 1.6 MUg/g for faeces. We conclude that this ELISA is sufficiently linear, accurate, precise, and reproducible for clinical evaluation. PMID- 22074687 TI - Food restriction increases acquisition, persistence and drug prime-induced expression of a cocaine-conditioned place preference in rats. AB - Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. PMID- 22074689 TI - Structural analysis of zeolite NaA synthesized by a cost-effective hydrothermal method using kaolin and its use as water softener. AB - Zeolite 4A (LTA) has been successfully synthesized by a hydrothermal method, where kaolin was used as silica and alumina source. The synthesized zeolite was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), laser granulometry, and FTIR spectroscopy. XRD data from the Rietveld refinement method confirmed only one crystallographic phase. Zeolite A morphology was observed by SEM analysis, and it showed well-defined crystals with slightly different sizes but with the same cubic shape. Particle size distribution of the crystals was confirmed by laser granulometry, whereas FTIR spectroscopy revealed significant structural differences between the starting material and the final zeolite product used as water softener. PMID- 22074690 TI - Facile fabrication of a superamphiphobic surface on the copper substrate. AB - A simple solution-immersion technique was developed for the fabrication of a superamphiphobic surface on the copper sheet. Hierarchical structure composed of nanorod arrays and microflowers was formed on the copper surface by an alkali assistant oxidation process; after fluorination, the surface became super repellent toward water and several organic liquids possessing much lower surface tension than that of water, such as hexadecane. Such superamphiphobicity is attributed to the synergistic effect of their special surface chemicals and microscopic structures, which allows for the formation of a composite interface with all probing liquids tested. We also discuss the effects of surface chemical constituent and geometrical structure on hydrophobicity and oleophobicity; such information allows us to engineer surfaces with specific oleophobic behavior. Additionally, the stability of the composite interface on the created superamphiphobic surface is studied by the compression and immersion test. PMID- 22074691 TI - Fabrication of hierarchical microparticles by depositing the in situ synthesized surface nanoparticles on microspheres during the seed emulsion polymerization. AB - A general strategy for the synthesis of polymeric hierarchical microparticles containing surface nanoparticles through modified seed emulsion polymerization is proposed. This modified seed emulsion polymerization has a character that suitable amount of monomer miniemulsion is added during the polymerization. The in situ synthesized surface nanoparticles which are resulted from the monomer miniemulsion as well as the shell-forming polymer coagulate on the seed particles and therefore hierarchical microparticles are fabricated. Various polymeric hierarchical microparticles containing 20-36 nm poly(styrene-co-acrylamide), poly(styrene-co-acrylic acid), and polystyrene surface nanoparticles are synthesized following the proposed method. The advantages in the present synthesis including both the well controls in the size, the composition, and the number of the surface nanoparticles and the convenience are demonstrated. The proposed strategy is anticipated to be a general method to fabricate hierarchical microparticles and is believed to have promising application in particle surface modification. PMID- 22074692 TI - Cobalt (II) chloride promoted formation of honeycomb patterned cellulose acetate films. AB - CoCl(2) containing honeycomb patterned films were prepared from cellulose acetate (CA)/CoCl(2)/acetone solutions by the breath figure method in a wide range of humidities. Size and pore regularity depend on the CA/CoCl(2) molar ratio and humidity. When replacing CoCl(2) with Co(NO(3))(2) or CoBr(2), no formation of ordered porosity in the cellulose acetate films is observed. According to data from scanning electron microscopy (SEM), Energy Dispersive X-ray Microanalysis (EDX), X-ray Diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, the key role in the formation of honeycomb structures can be attributed to the physical and chemical properties of CoCl(2) - hygroscopicity, low interaction with CA, and extraction from CA/CoCl(2)/acetone solution by water droplets condensed on the surface of the CA/CoCl(2) solution. Obtained films are prospective for using in catalysis, hydrogen fuel cells, and optical sensing materials. PMID- 22074693 TI - Multi-functional nanopatterned optical films fabricated using capillary force lithography. AB - We demonstrate anisotropic optical films based on liquid crystalline polymer (LCP) using a capillary force lithography (CFL). The fabricated optical films can be used as both an optical component and a self-aligning capability of liquid crystal molecules introduced on the film. Additionally, HA or PA LC can be induced on same material by controlling the water repellency of LCP surface. Moreover, surface anchoring transitions could be controlled by variation of pattern sizes and surface treatment. In this point of view, one thin optical film can act both retarder and alignment layer and then shows good retardation, LC alignment, and transmittance at the same time. PMID- 22074694 TI - Immobilization of poly(fluorene) within clay nanocomposite: an easy way to control keto defect. AB - Blue light emitting cationic polyfluorene polymer(PF)/montmorillonite (MMT) nanocomposites were prepared by solution intercalation and exfoliation method to evaluate the effect of MMT on the nanocomposite structures, properties and morphologies. The properties of PF-MMT composites, containing 1-50 mass% MMT, were characterized unambiguously with the help of multiple analytical techniques, with focus on the keto defect and photostability of PF in the nanocomposites. XRD and HRTEM studies reveal both exfoliation of MMT galleries at lower content of MMT in composites and intercalation of PF chains into the MMT galleries at higher MMT content. The nanocomposites show higher thermal stability than pristine PF as anchorage of nanoclay in PF matrix occur through the electrostatic interaction between nanoclay and polymer. The decrease in Si-O-Si stretching frequency during exfoliation is much higher than in intercalation, as Si-O-Si experience lesser hindrance to vibrate in exfoliated MMT galleries. The gradual redshift of pi pi(*) transition peak of PF with increasing MMT content in composites confirms the uncoiling of PF in clay galleries. The photoluminescence characteristics reveal interruption of interchain interaction in this intercalated and exfoliated organic/inorganic hybrid system, which reduces the low-energy emission that results from keto defect. Due to very high aspect ratio of MMT, it can act as an efficient exciton blocking layer and a barrier to oxygen diffusion, which may lead to a device with high color purity and enhanced photostability. Again current-voltage characteristics of nanocomposite films confirm the retention of LED properties after nanocomposite formation. PMID- 22074695 TI - Comment: Aris and Leblanc "Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada". PMID- 22074696 TI - Longitudinal changes in PON1 activities, PON1 phenotype distribution and oxidative status throughout normal pregnancy. AB - The purpose of the present study was to determine changes in plasma paraoxonase-1 activity (an indicator of paraoxonase phenotype) throughout normal pregnancy and its relationship with maternal oxidative stress status. The frequencies of the paraoxonase-1 phenotype in the studied population were determined using a two substrate (paraoxon/diazoxon) activity method. As a parameter of oxidative stress status we measured the redox balance. Paraoxonase-1 activity significantly decreased at gestational week 32. In addition, the lipid profile was more atherogenic. Redox balance was significantly increased across gestational weeks. There were independent direct associations between maternal smoking habits before pregnancy, glucose concentrations and redox balance with PON1 activity in the third trimester. This study shows that pregnancy is followed by a decrease in PON1 activity and increased risk for development of cardiovascular diseases. We conclude that changes in paraoxonase-1 status during pregnancy are associated with maternal oxidative stress status and smoking habits. PMID- 22074697 TI - Acute reproductive toxicity of 3,3'-iminodipropionitrile in female rats. AB - A potent neurotoxin 3,3'-iminodipropionitrile (IDPN), which is an occupational exposure hazard in industry, induces persistent behavioral abnormalities in experimental animals; however, its reproductive toxicity has not been determined. Therefore, we assessed the toxicity of IDPN in the reproductive system of female rats. A single intraperitoneal injection of IDPN (1000 mg/kg body weight) into female Wistar-Imamichi rats caused acute estrous cycle arrest at diestrus for up to 15 days. The arrest was accompanied by follicular atresia, and following arrest, the estrous cycle and ovarian morphology recovered. Ovarian mRNA levels of growth differentiation factor 9 and Fas ligand, a cell death marker, transiently increased following IDPN injection, but eventually they returned to basal levels. IDPN added to in vitro cultures of ovarian follicles also induced the expression of these genes, indicating that IDPN directly promoted ovarian cell death. PMID- 22074698 TI - Erosive pustular dermatosis of the scalp: a review with a focus on dapsone therapy. AB - BACKGROUND: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory disorder of unknown origin characterized by pustules, erosions, and crusting in areas of alopecia that tend to be atrophic, actinically damaged, or both. The most common treatments reported include antibiotics and topical anti inflammatories, which can be ineffective. In the search for effective treatment for EPDS, we share our experience with topical dapsone 5% gel. OBSERVATIONS: We present 4 patients with EPDS, all with classic clinical presentations and histologic findings of EPDS, who had failed a variety of treatments including oral, intralesional, or topical steroids, tacrolimus, and antibiotics. All patients demonstrated rapid improvement or resolution with topical dapsone 5% gel. LIMITATIONS: Our experience and success with topical dapsone for EPDS is observational and not the result of a randomized controlled trial. CONCLUSION: Our observations demonstrate topical dapsone 5% gel to be a novel, safe, and efficacious therapeutic alternative for mild to moderate EPDS. PMID- 22074699 TI - Systematic skin cancer screening in Northern Germany. AB - BACKGROUND: The incidence of skin cancer is increasing worldwide. For decades, opportunistic melanoma screening has been carried out to respond to this burden. However, despite potential positive effects such as reduced morbidity and mortality, there is still a lack of evidence for feasibility and effectiveness of organized skin cancer screening. OBJECTIVE: The main aim of the project was to evaluate the feasibility of systematic skin cancer screening. METHODS: In 2003, the Association of Dermatological Prevention was contracted to implement the population-based SCREEN project (Skin Cancer Research to Provide Evidence for Effectiveness of Screening in Northern Germany) in the German state of Schleswig Holstein. A two-step program addressing malignant melanoma and nonmelanocytic skin cancer was implemented. Citizens (aged >= 20 years) with statutory health insurance were eligible for a standardized whole-body examination during the 12 month study period. Cancer registry and mortality data were used to assess first effects. RESULTS: Of 1.88 million eligible citizens, 360,288 participated in SCREEN. The overall population-based participation rate was 19%. A total of 3103 malignant skin tumors were found. On the population level, invasive melanoma incidence increased by 34% during SCREEN. Five years after SCREEN a substantial decrease in melanoma mortality was seen (men: observed 0.79/100,000 and expected 2.00/100,000; women: observed 0.66/100,000 and expected 1.30/100,000). LIMITATIONS: Because of political reasons (resistance as well as lack of support from major German health care stakeholders), it was not possible to conduct a randomized controlled trial. CONCLUSIONS: The project showed that large-scale systematic skin cancer screening is feasible and has the potential to reduce skin cancer burden, including mortality. Based on the results of SCREEN, a national statutory skin cancer early detection program was implemented in Germany in 2008. PMID- 22074701 TI - Deleterious impact of elaidic fatty acid on ABCA1-mediated cholesterol efflux from mouse and human macrophages. AB - Consumption of trans fatty acids (TFA) increase cardiovascular risk more than do saturated FA, but the mechanisms explaining their atherogenicity are still unclear. We investigated the impact of membrane incorporation of TFA on cholesterol efflux by exposing J774 mouse macrophages or human monocyte-derived macrophages (HMDM) to media enriched or not (standard medium) with industrially produced elaidic (trans-9 18:1) acid, naturally produced vaccenic (trans-11 18:1) acid (34 h, 70 MUM) or palmitic acid. In J774 macrophages, elaidic and palmitic acid, but not vaccenic acid, reduced ABCA1-mediated efflux by ~23% without affecting aqueous diffusion, SR-BI or ABCG1-mediated pathways, and this effect was maintained in cholesterol-loaded cells. The impact of elaidic acid on the ABCA1 pathway was weaker in cholesterol-normal HMDM, but elaidic acid induced a strong reduction of ABCA1-mediated efflux in cholesterol-loaded cells (-36%). In J774 cells, the FA supplies had no impact on cellular free cholesterol or cholesteryl ester masses, the abundance of ABCA1 mRNA or the total and plasma membrane ABCA1 protein content. Conversely, TFA or palmitic acid incorporation induced strong modifications of the membrane FA composition with a decrease in the ratio of (cis-monounsaturated FA+polyunsaturated FA):(saturated FA+TFA), with elaidic and vaccenic acids representing each 20% and 13% of the total FA composition, respectively. Moreover, we demonstrated that cellular ATP was required for the effect of elaidic acid, suggesting that it contributes to atherogenesis by impairing ABCA1-mediated cholesterol efflux in macrophages, likely by decreasing the membrane fluidity, which could thereby reduce ATPase activity and the function of the transporter. PMID- 22074700 TI - LBH-589 (panobinostat) potentiates fludarabine anti-leukemic activity through a JNK- and XIAP-dependent mechanism. AB - Effects of the HDAC inhibitor LBH-589 (panobinostat) on fludarabine lethality toward acute myeloid leukemia (AML) cells were examined in vitro and in vivo. LBH 589 pretreatment sensitized U937, HL-60, and primary leukemia cells to fludarabine while blocking NF-kappaB activation accompanied by XIAP down regulation and JNK activation. Pharmacologic or genetic JNK inhibition significantly attenuated LBH-589/fludarabine lethality, whereas XIAP over expression diminished JNK activation and apoptosis. Combined in vivo treatment abrogated leukemia growth in a U937 xenograft murine model and substantially increased animal survival. These studies highlight the interplay between NF kappaB activation, XIAP down-regulation, and JNK activation in anti-leukemic synergism between fludarabine and LBH-589. PMID- 22074702 TI - Inhibition of Pim1 kinase activation attenuates allergen-induced airway hyperresponsiveness and inflammation. AB - Pim kinases are a family of serine/threonine kinases whose activity can be induced by cytokines involved in allergy and asthma. These kinases play a role in cell survival and proliferation, but have not been examined, to the best of our knowledge, in the development of allergic disease. This study sought to determine the role of Pim1 kinase in the development of allergic airway responses. Mice were sensitized and challenged with antigen (primary challenge), or were sensitized, challenged, and rechallenged with allergen in a secondary model. To assess the role of Pim1 kinase, a small molecule inhibitor was administered orally after sensitization and during the challenge phase. Airway responsiveness to inhaled methacholine, airway and lung inflammation, cell composition, and cytokine concentrations were assessed. Lung Pim1 kinase concentrations were increased after ovalbumin sensitization and challenge. In the primary allergen challenge model, treatment with the Pim1 kinase inhibitor after sensitization and during airway challenges prevented the development of airway hyperresponsiveness, eosinophilic airway inflammation, and goblet cell metaplasia, and increased Th2 cytokine concentrations in bronchoalveolar fluid in a dose-dependent manner. These effects were also demonstrated after a secondary allergen challenge, where lung allergic disease was established before treatment. After treatment with the inhibitor, a significant reduction was evident in the number of CD4(+) and CD8(+) T cells and concentrations of cytokines in the airways. The inhibition of Pim1 kinase was effective in preventing the development of airway hyperresponsiveness, airway inflammation, and cytokine production in allergen-sensitized and allergen challenged mice. These data identify the important role of Pim1 kinase in the full development of allergen-induced airway responses. PMID- 22074703 TI - Nutritional stress and arginine auxotrophy confer high sensitivity to chloroquine toxicity in mesothelioma cells. AB - The correlation between cell sensitivity to autophagy inhibitors, such as chloroquine (CQ), and the expression/activity of molecules involved in the control and execution of autophagy is well documented. However, tumor cells with comparable autophagic potentials may display variable degrees of autophagy addiction, due to the differential expression of molecular determinants, which are still scarcely defined. In this study, we investigated the effects of CQ on growth, death, and autophagic activity of malignant mesothelioma cell lines cultured in standard versus nutritional stress conditions partially mimicking those found in the tumor microenvironment. We report that, in each cell line, the toxic effects of CQ were amplified by nutritional stress and paralleled by autophagy inhibition. Still, the cell lines displayed different levels of sensitivity to CQ toxicity, which did not correlate with their relative degrees of constitutive and nutritional stress-induced autophagy, nor with the relative magnitude of the autophagy inhibition induced by the drug. Thus, we tested the hypothesis that the cell lines' sensitivity to CQ was related to their variable dependence on recycling of intracellular constituents by autophagy. In fact, the cell line with the highest sensitivity to the toxic effects of CQ was auxotrophic for arginine, due to the deficient expression of the enzyme argininosuccinate synthetase (ASS). Furthermore, overexpression of ASS in these cells reduced their sensitivity to CQ toxicity. Based on these results, the assessment of ASS expression in malignant mesothelioma tissues may allow the identification of subgroups of tumors with an increased sensitivity to the toxic effects of this drug. PMID- 22074705 TI - A comparison of the Ex-PRESSTM mini glaucoma shunt with standard trabeculectomy in the surgical treatment of glaucoma. AB - BACKGROUND AND OBJECTIVE: To compare the success and complication rates of patients with glaucoma who had an Ex-PRESS mini glaucoma shunt device implantation (Optonol, Ltd., Neve Ilan, Israel) to those who had conventional trabeculectomy. PATIENTS AND METHODS: The records of 76 eyes of 69 consecutive subjects who had Ex-PRESS implants and 77 eyes of 65 consecutive controls who had trabeculectomy procedures were reviewed. All surgeries were performed by one of the authors (LWH). Success was defined as an intraocular pressure (IOP) between 5 and 21 mm Hg in patients who did not require further glaucoma surgery in the eye of note. RESULTS: The difference in the percentage of cases of postoperative hypotony between the standard trabeculectomy group (16%) and the Ex-PRESS group (4%) was statistically significant (P = .023). CONCLUSION: The Ex-PRESS device is at least as effective as the standard trabeculectomy in lowering the IOP of patients with glaucoma, with a significantly lower risk of postoperative hypotony. The data further suggest that the Ex-PRESS device results in an overall greater percentage reduction in IOP than with trabeculectomy, although this did not reach statistical significance. PMID- 22074704 TI - Proteomic footprinting of drug-treated cancer cells as a measure of cellular vaccine efficacy for the prevention of cancer recurrence. AB - The comparative proteomic study of cell surfaces of native and drug-treated cancer cells was performed. To this end, cell proteomic footprinting, which reflects the mass spectrometry profiling of cell surface proteins, was applied to breast adenocarcinoma cells (MCF-7), which were untreated or treated with doxorubicin, tamoxifen, or etoposide. The footprints of drug-treated cells were compared with the footprints of untreated cells and the footprint of a randomly selected control cancer cell culture. It was found that drug-treated cells have reproducible, pronounced, and drug-specific changes in cell surface protein expression. Cytotoxicity assays, which are an in vitro model of human antitumor vaccination, revealed that the degree of these changes correlates directly with the ability of the cancer cells to escape cell death induced by a cytotoxic T cell-mediated immune response. Moreover, cancer cells escape from the immune response was linearly approximated (R(2) equal to 0.99) with the degree by which their proteomic footprints diverged from the footprint of the targeted (native) cancer cells. From these findings, it was concluded that the design of anticancer vaccines intended to prevent cancer recurrence after primary treatment should consider the drug-specific changes in cancer cell-surface antigens. Such changes can be easily identified by cell proteomic footprinting, renewing hopes for development of efficient cellular cancer vaccines. PMID- 22074706 TI - Intracuring: intrastromal corneal application of dental flowable composite. AB - BACKGROUND AND OBJECTIVE: To evaluate an intracuring method by changing the corneal curvature. MATERIALS AND METHODS: An intrastromal tunnel was created by femtosecond laser in five cadaveric sheep eyes. Dental flowable restorative composite was used to fill the tunnel. A light-emitting diode light was applied for polymerization for 20 seconds. Flat plastic material was used for pressure on the cornea during polymerization. Keratometric measurements were obtained in all eyes using a rotating Scheimpflug camera. RESULTS: Remarkable changes on the corneal curvature were observed after the intracuring method. Inferior or inferonasal flattening and opposite steepening was observed in all sheep eyes. The average flattening effect of this method was 10.6 diopters. CONCLUSION: This new application may be a promising technique for the treatment of keratoconus. The application of this technique in humans could offer improved treatment options in the future. PMID- 22074707 TI - Passive silicone oil removal in 23-gauge transconjunctival vitrectomy. AB - The authors introduce a feasible technique of passive silicone oil removal via the pars plana using 23-gauge transconjunctival vitrectomy microsurgery instruments. The procedure consists of three-port transconjunctival insertion of 23-gauge microcannulas. An inferotemporal cannula is connected to an infusion line and the height of the bottle is raised. The other two open ports are used to remove intravitreal silicone oil with an externally applied cotton swab. Passive silicone oil removal was conducted using the 23-gauge system in 46 phakic or pseudophakic eyes with silicone oil of both 1,000 (n = 39) and 5,000 centistokes (n = 7). A suture was placed for one of three sclera entry sites in 17 eyes. Cataract extraction with phacoemulsification was combined with passive silicone oil removal in 14 eyes. Transient hypotony was observed in 2 eyes. No retinal redetachment or other procedure-related complications were encountered. PMID- 22074708 TI - A new biconcave contact lens for vitrectomy in eyes with intraocular lens implantation. AB - The authors report a new biconcave contact lens capable of providing superior surgical views of eyes during vitrectomy and intraocular lens implantation under both fluid-filled and air-filled conditions. The new biconcave lens is made of a glass with a high refractive index (nd = 1.883). The lens is placed on the cornea using a regular lens ring for the floating vitrectomy lens system. During vitrectomy, the new biconcave lens provides a view as clear as that of the commercially available flat-concave lens when the vitreous cavity is filled with fluid. The lens also provides a more magnified view than the commercially sold biconcave lens during fluid-air exchange, with no need for replacement. The new biconcave vitrectomy lens spares the surgeon the trouble of replacing different refractive lenses during the fluid-air exchange procedure in an eye undergoing intraocular lens implantation, and may be helpful for vitreous surgery. PMID- 22074709 TI - Redox states of plastids and mitochondria differentially regulate intercellular transport via plasmodesmata. AB - Recent studies suggest that intercellular transport via plasmodesmata (PD) is regulated by cellular redox state. Until now, this relationship has been unclear, as increased production of reactive oxygen species (ROS) has been associated with both increased and decreased intercellular transport via PD. Here, we show that silencing two genes that both increase transport via PD, INCREASED SIZE EXCLUSION LIMIT1 (ISE1) and ISE2, alters organelle redox state. Using redox-sensitive green fluorescent proteins targeted to the mitochondria or plastids, we show that, relative to wild-type leaves, plastids are more reduced in both ISE1- and ISE2 silenced leaves, whereas mitochondria are more oxidized in ISE1-silenced leaves. We further show that PD transport is positively regulated by ROS production in mitochondria following treatment with salicylhydroxamic acid but negatively regulated by an oxidative shift in both chloroplasts and mitochondria following treatment with paraquat. Thus, oxidative shifts in the mitochondrial redox state positively regulate intercellular transport in leaves, but oxidative shifts in the plastid redox state counteract this effect and negatively regulate intercellular transport. This proposed model reconciles previous contradictory evidence relating ROS production to PD transport and supports accumulating evidence that mitochondria and plastids are crucial regulators of PD function. PMID- 22074710 TI - Diagnosis and management of colorectal cancer: summary of NICE guidance. PMID- 22074712 TI - Antiretroviral therapy programmes in resource limited settings. PMID- 22074711 TI - Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial. AB - OBJECTIVE: To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda. DESIGN: Randomised clinical trial SETTING: A home based ART programme in rural Uganda. PARTICIPANTS: All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells * 10(6)/L or World Health Organization stage 3 or 4 disease. INTERVENTIONS: Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone). MAIN OUTCOME MEASURES: Serious morbidity (newly diagnosed AIDS defining illness) and mortality. RESULTS: 1094 participants started ART; median CD4 count at baseline was 129 cells * 10(6)/L. Median follow up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P = 0.002) or the CD4 arm (1.49, P = 0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P = 0.31). CONCLUSION: In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093. PMID- 22074714 TI - Words are all we have. PMID- 22074713 TI - CD4 cell count and viral load monitoring in patients undergoing antiretroviral therapy in Uganda: cost effectiveness study. AB - OBJECTIVE: To examine the cost and cost effectiveness of quarterly CD4 cell count and viral load monitoring among patients taking antiretroviral therapy (ART). DESIGN: Cost effectiveness study. SETTING: A randomised trial in a home based ART programme in Tororo, Uganda. PARTICIPANTS: People with HIV who were members of the AIDS Support Organisation and had CD4 cell counts <250 * 10(6) cells/L or World Health Organization stage 3 or 4 disease. MAIN OUTCOME MEASURES: Outcomes calculated for the study period and projected 15 years into the future included costs, disability adjusted life years (DALYs), and incremental cost effectiveness ratios (ICER; $ per DALY averted). Cost inputs were based on the trial and other sources. Clinical inputs derived from the trial; in the base case, we assumed that point estimates reflected true differences even if non-significant. We conducted univariate and multivariate sensitivity analyses. INTERVENTIONS: Three monitoring strategies: clinical monitoring with quarterly CD4 cell counts and viral load measurement (clinical/CD4/viral load); clinical monitoring and quarterly CD4 counts (clinical/CD4); and clinical monitoring alone. RESULTS: With the intention to treat (ITT) results per 100 individuals starting ART, we found that clinical/CD4 monitoring compared with clinical monitoring alone increases costs by $20,458 (L12,780, ?14,707) and averts 117.3 DALYs (ICER = $174 per DALY). Clinical/CD4/viral load monitoring compared with clinical/CD4 monitoring adds $142,458, and averts 27.5 DALYs ($5181 per DALY). The superior ICER for clinical/CD4 monitoring is robust to uncertainties in input values, and that strategy is dominant (less expensive and more effective) compared with clinical/CD4/viral load monitoring in one quarter of simulations. If clinical inputs are based on the as treated analysis starting at 90 days (after laboratory monitoring was initiated), then clinical/CD4/viral load monitoring is dominated by other strategies. CONCLUSIONS: Based on this trial, compared with clinical monitoring alone, monitoring of routine CD4 cell count is considerably more cost effective than additionally including routine viral load testing in the monitoring strategy and is more cost effective than ART. PMID- 22074715 TI - Policy determines drinking behaviour, says expert on addiction. PMID- 22074716 TI - Divergent postnatal development of the carotid body in DBA/2J and A/J strains of mice. AB - We have previously shown that the adult DBA/2J and A/J strains of mice differ in carotid body volume and morphology. The question has arisen whether these differences develop during the prenatal or postnatal period. Investigating morphological development of the carotid body and contributing genes in these mice can provide further understanding of the appropriate formation of the carotid body. We examined the carotid body of these mice from 1 day to 4 wk old for differences in volume, morphology, and gene expression of Gdnf family, Dlx2, Msx2, and Phox2b. The two strains showed divergent morphology starting at 1 wk old. The volume of the carotid body increased from 1 wk up to 2 wk old to the level of 4 wk old in the DBA/2J mice but not in the A/J mice. This corresponds with immunoreactivity of LC3, an autophagy marker, in A/J tissues at 10 days and 2 wk. The differences in gene expression were examined at 1 wk, 10 days, and 2 wk old, because divergent growth occurred during this period. The DBA/2J's carotid body at 1 wk old showed a greater expression of Msx2 than the A/J's carotid body. No other candidate genes showed consistent differences between the ages and strains. The difference was not seen in sympathetic cervical ganglia of 1 wk old, suggesting that the difference is carotid body specific. The current study indicates the critical postnatal period for developing distinctive morphology of the carotid body in these mice. Further studies are required to further elucidate a role of Msx2 and other uninvestigated genes. PMID- 22074717 TI - Endurance exercise attenuates ventilator-induced diaphragm dysfunction. AB - Controlled mechanical ventilation (MV) is a life-saving measure for patients in respiratory failure. However, MV renders the diaphragm inactive leading to diaphragm weakness due to both atrophy and contractile dysfunction. It is now established that oxidative stress is a requirement for MV-induced diaphragmatic proteolysis, atrophy, and contractile dysfunction to occur. Given that endurance exercise can elevate diaphragmatic antioxidant capacity and the levels of the cellular stress protein heat shock protein 72 (HSP72), we hypothesized that endurance exercise training before MV would protect the diaphragm against MV induced oxidative stress, atrophy, and contractile dysfunction in female Sprague Dawley rats. Our results confirm that endurance exercise training before MV increased both HSP72 and the antioxidant capacity in the diaphragm. Importantly, compared with sedentary animals, exercise training before MV protected the diaphragm against MV-induced oxidative damage, protease activation, myofiber atrophy, and contractile dysfunction. Further, exercise protected diaphragm mitochondria against MV-induced oxidative damage and uncoupling of oxidative phosphorylation. These results provide the first evidence that exercise can provide protection against MV-induced diaphragm weakness. These findings are important and establish the need for future experiments to determine the mechanism(s) responsible for exercise-induced diaphragm protection. PMID- 22074718 TI - A novel vascular clip design for the reliable induction of 2-kidney, 1-clip hypertension in the rat. AB - The 2-kidney, 1-clip (2K1C) model has provided many insights into the pathogenesis of renovascular hypertension. However, studies using the 2K1C model often report low success rates of hypertension, with typical success rates of just 40-60%. We hypothesized that these low success rates are due to fundamental design flaws in the clips traditionally used in 2K1C models. Specifically, the gap widths of traditional silver clips may not be maintained during investigator handling and these clips may also be easily dislodged from the renal artery following placement. Therefore, we designed and tested a novel vascular clip possessing design features to maintain both gap width and position around the renal artery. In this initial study, application of these new clips to the left renal artery produced reliable and consistent levels of hypertension in rats. Nine-day application of clips with gap widths of 0.27, 0.25, and 0.23 mm elicited higher mean arterial blood pressures of 112 +/- 4, 121 +/- 6, and 135 +/- 7 mmHg, respectively (n = 8 for each group), than those of sham-operated controls (95 +/- 2 mmHg, n = 8). Moreover, 8 out of 8 rats in each of the 0.23 and 0.25 mm 2K1C groups were hypertensive, whereas 7 out of 8 rats in the 0.27 mm 2K1C group were hypertensive. Plasma renin concentrations were also increased in all 2K1C groups compared with sham-operated controls. In summary, this novel clip design may help eliminate the large degree of unreliability commonly encountered with the 2K1C model. PMID- 22074719 TI - Precursors and inhibitors of hydrogen sulfide synthesis affect acute hypoxic pulmonary vasoconstriction in the intact lung. AB - The effects of hydrogen sulfide (H(2)S) and acute hypoxia are similar in isolated pulmonary arteries from various species. However, the involvement of H(2)S in hypoxic pulmonary vasoconstriction (HPV) has not been studied in the intact lung. The present study used an intact, isolated, perfused rat lung preparation to examine whether adding compounds essential to H(2)S synthesis or to its inhibition would result in a corresponding increase or decrease in the magnitude of HPV. Western blots performed in lung tissue identified the presence of the H(2)S-synthesizing enzymes, cystathionine gamma-lyase (CSE) and 3 mercaptopyruvate sulfur transferase (3-MST), but not cystathionine beta-synthase (CBS). Adding three H(2)S synthesis precursors, cysteine and oxidized or reduced glutathione, to the perfusate significantly increased peak arterial pressure during hypoxia compared with control (P < 0.05). Adding alpha-ketoglutarate to enhance the 3-MST enzyme pathway also resulted in an increase (P < 0.05). Both aspartate, which inhibits the 3-MST synthesis pathway, and propargylglycine (PPG), which inhibits the CSE pathway, significantly reduced the increases in arterial pressure during hypoxia. Diethylmaleate (DEM), which conjugates sulfhydryls, also reduced the peak hypoxic arterial pressure at concentrations >2 mM. Finally, H(2)S concentrations as measured with a specially designed polarographic electrode decreased markedly in lung tissue homogenate and in small pulmonary arteries when air was added to the hypoxic environment of the measurement chamber. The results of this study provide evidence that the rate of H(2)S synthesis plays a role in the magnitude of acute HPV in the isolated perfused rat lung. PMID- 22074720 TI - Tracheal occlusions evoke respiratory load compensation and neural activation in anesthetized rats. AB - Airway obstruction in animals leads to compensation and avoidance behavior and elicits respiratory mechanosensation. The pattern of respiratory load compensation and neural activation in response to intrinsic, transient, tracheal occlusions (ITTO) via an inflatable tracheal cuff are unknown. We hypothesized that ITTO would cause increased diaphragm activity, decreased breathing frequency, and activation of neurons within the medullary and pontine respiratory centers without changing airway compliance. Obstructions were performed for 2-3 breaths followed by a minimum of 15 unobstructed breaths with an inflatable cuff sutured around the trachea in rats. The obstruction procedure was repeated for 10 min. The brains of obstructed and control animals were removed, fixed, sectioned, and stained for c-Fos. Respiratory pattern was measured from esophageal pressure (P(es)) and diaphragm electromyography (EMG(dia)). The obstructed breaths resulted in a prolonged inspiratory and expiratory time, an increase in EMG(dia) amplitude, and a more negative P(es) compared with control breaths. Neurons labeled with c-Fos were found in brain stem and suprapontine nuclei, with a significant increase in c-Fos expression for the occluded experimental group compared with the control groups in the nucleus ambiguus, nucleus of the solitary tract, lateral parabrachial nucleus, and periaqueductal gray matter. The results of this study demonstrate tracheal occlusion-elicited activation of neurons in brain stem respiratory nuclei and neural areas involved in stress responses and defensive behaviors, suggesting that these neurons mediate the load compensation breathing pattern response and may be part of the neural pathway for respiratory mechanosensation. PMID- 22074721 TI - In situ methods for assessing alveolar mechanics. AB - Lung mechanics are an important determinant of physiological and pathophysiological lung function. Recent light microscopy studies of the intact lung have furthered the understanding of lung mechanics but used methodologies that may have introduced artifacts. To address this concern, we employed a short working distance water immersion objective to capture confocal images of a fluorescently labeled alveolar field on the costal surface of the isolated, perfused rat lung. Surface tension held a saline drop between the objective tip and the lung surface, such that the lung surface was unconstrained. For comparison, we also imaged with O-ring and coverslip; with O-ring, coverslip, and vacuum pressure; and without perfusion. Under each condition, we ventilated the lung and imaged the same region at the endpoints of ventilation. We found use of a coverslip caused a minimal enlargement of the alveolar field; additional use of vacuum pressure caused no further dimensional change; and absence of perfusion did not affect alveolar field dimension. Inflation-induced expansion was unaltered by methodology. In response to inflation, percent expansion was the same as recorded by all four alternative methods. PMID- 22074722 TI - Diabetes incidence and long-term exposure to air pollution: a cohort study. AB - OBJECTIVE: Animal and cross-sectional epidemiological studies suggest a link between air pollution and diabetes, whereas the limited prospective data show mixed results. We studied the association between long-term exposure to traffic related air pollution and incidence of diabetes. RESEARCH DESIGN AND METHODS: We followed 57,053 participants of the Danish Diet, Cancer, and Health cohort in the Danish National Diabetes Register between baseline (1993-1997) and 27 June 2006. We estimated the mean levels of nitrogen dioxide (NO(2)) at the residential addresses of the cohort participants since 1971 and modeled the association between NO(2) and diabetes incidence with a Cox regression model, separately for two definitions of diabetes: all cases and a more strict definition where unconfirmed cases were excluded. RESULTS: Over a mean follow-up of 9.7 years of 51,818 eligible subjects, there were 4,040 (7.8%) incident diabetes cases in total and 2,877 (5.5%) with confirmed diagnoses. Air pollution was not associated with all diabetes cases (hazard ratio 1.00 [95% CI 0.97-1.04] per interquartile range of 4.9 MUg/m(3) mean NO(2) levels since 1971), but a borderline statistically significant association was detected with confirmed cases of diabetes (1.04 [1.00-1.08]). Among confirmed diabetes cases, effects were significantly enhanced in nonsmokers (1.12 [1.05-1.20]) and physically active people (1.10 [1.03-1.16]). CONCLUSIONS: Long-term exposure to traffic-related air pollution may contribute to the development of diabetes, especially in individuals with a healthy lifestyle, nonsmokers, and physically active individuals. PMID- 22074723 TI - Dietary patterns during adolescence and risk of type 2 diabetes in middle-aged women. AB - OBJECTIVE Whether dietary habits early in life can affect risk of type 2 diabetes (T2DM) in adulthood is unknown. We evaluated the relationship between dietary patterns during adolescence and risk of T2DM in midlife. RESEARCH DESIGN AND METHODS We examined the 7-year incidence of T2DM in relation to dietary patterns during high school among 37,038 participants in the Nurses' Health Study II cohort, who completed a food-frequency questionnaire about their diet during high school. Dietary patterns were derived by factor analysis. Cox proportional hazards regression was used to estimate relative risk (RR) and 95% CI. RESULTS The prudent pattern, characterized by healthy foods, was not associated with risk of T2DM. The Western pattern, characterized by desserts, processed meats, and refined grains, was associated with 29% greater risk of T2DM (RR 1.29; 95% CI 1.00-1.66; P trend 0.04), after adjusting for high school and adult risk factors comparing extreme quintiles, but was attenuated after adjusting for adult weight change (1.19; 0.92-1.54). Women who had high Western pattern scores in high school and adulthood had an elevated risk of T2DM compared with women who had consistent low scores (1.82; 1.35-2.45), and this association was partly mediated by adult BMI (1.15; 0.85-1.56). CONCLUSIONS A Western dietary pattern during adolescence may increase risk of T2DM in later life, partly through adult weight gain. Preventive measures should be aimed at developing healthy dietary habits that begin in early life and continue through adulthood. PMID- 22074724 TI - Piloting a novel algorithm for glucose control in the coronary care unit: the RECREATE (REsearching Coronary REduction by Appropriately Targeting Euglycemia) trial. AB - OBJECTIVE: Elevated glucose levels are common after an acute myocardial infarction (AMI) and increase the risk of death. Prior trials of glucose control after AMI have been inconsistent in their ability to lower glucose levels and have reported mixed effects on mortality. We developed a paper-based glucose lowering algorithm and assessed its feasibility and safety in the setting of AMI. RESEARCH DESIGN AND METHODS: A total of 287 participants with an acute ST segment elevation myocardial infarction (STEMI) and a capillary glucose level >=8.0 mmol/L were randomly allocated to glucose management with intravenous glulisine insulin using this algorithm in the coronary care unit (CCU), followed by once daily subcutaneous insulin glargine for 30 days versus standard glycemic approaches. The primary outcome was a difference in mean glucose levels at 24 h. Participants were followed for clinical outcomes through 90 days. RESULTS: At 24 h, the mean glucose level was 1.41 mmol/L (95% CI 0.69-2.13) lower in the insulin (6.53 vs. 7.94 mmol/L). Differences in glucose levels were maintained at 72 h and 30 days. A total of 22.7% of the insulin group versus 4.4% of the standard group had biochemical hypoglycemia (with neither signs nor symptoms) in the CCU because of lower glycemic goals. However, there were no differences in symptomatic hypoglycemia or clinical outcomes between the groups. CONCLUSIONS: A paper-based insulin algorithm targeting glucose levels of 5.0-6.5 mmol/L (90-117 mg/dL) can be feasibly implemented in the CCU. A cardiovascular outcomes trial using this approach can determine whether targeted glucose lowering improves patient outcomes. PMID- 22074725 TI - Elevated admission glucose and mortality in patients with acute pulmonary embolism. AB - OBJECTIVE: Although associated with adverse outcomes in other cardiopulmonary conditions, the prognostic value of elevated glucose in patients with acute pulmonary embolism (PE) is unknown. We sought to examine the association between glucose levels and mortality and hospital readmission rates for patients with PE. RESEARCH DESIGN AND METHODS: We evaluated 13,621 patient discharges with a primary diagnosis of PE from 185 acute care hospitals in Pennsylvania (from January 2000 to November 2002). Admission glucose levels were analyzed as a categorical variable (<=110, >110-140, >140-170, >170-240, and >240 mg/dL). The outcomes were 30-day all-cause mortality and hospital readmission. We used random intercept logistic regression to assess the independent association between admission glucose levels and mortality and hospital readmission, adjusting for patient (age, sex, race, insurance, comorbid conditions, severity of illness, laboratory parameters, and thrombolysis) and hospital (region, size, and teaching status) factors. RESULTS: Elevated glucose (>110 mg/dL) was present in 8,666 (63.6%) patients. Patients with a glucose level <=110, >110-140, >140-170, >170 240, and >240 mg/dL had a 30-day mortality of 5.6, 8.4, 12.0, 15.6, and 18.3%, respectively (P < 0.001). Compared with patients with a glucose level <=110 mg/dL, the adjusted odds of dying were greater for patients with a glucose level >110-140 (odds ratio 1.19 [95% CI 1.00-1.42]), >140-170 (1.44 [1.17-1.77]), >170 240 (1.54 [1.26-1.90]), and >240 mg/dL (1.60 [1.26-2.03]), with no difference in the odds of hospital readmission. CONCLUSIONS: In patients with acute PE, elevated admission glucose is common and independently associated with short-term mortality. PMID- 22074726 TI - Improved metabolic control in children and adolescents with type 1 diabetes: a trend analysis using prospective multicenter data from Germany and Austria. AB - OBJECTIVE: To investigate the temporal trend of metabolic control and potential predictors in German and Austrian children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: This study is based on a large, multicenter database for prospective longitudinal documentation of diabetes care in Germany and Austria. Data from 30,708 patients documented in 305 diabetes centers between 1995 and 2009 were analyzed. Generalized linear mixed regression models were used to adjust trend analysis for relevant confounders. RESULTS: Unadjusted mean HbA(1c) decreased from 8.7 +/- 1.8% in 1995 to 8.1 +/- 1.5% in 2009. In multiple regression analysis, treatment year, age, sex, diabetes duration, migration background, BMI-SDS, and daily insulin dose were significant predictors of metabolic control (P < 0.001). After multiple adjustment, mean HbA(1c) decreased significantly by 0.038% per year (95% CI 0.032-0.043%), average odds ratio (OR) per year for HbA(1c) >7.5% (>9.0%) was 0.969 (95% CI 0.961-0.977) (0.948, 95% CI 0.941-0.956). Intensified insulin regimen was associated with lower frequency of poor metabolic control (HbA(1c) >9%; P = 0.005) but not with average HbA(1c) (P = 0.797). Rate of severe hypoglycemia and hypoglycemic coma decreased significantly (relative risk [RR] per year 0.948, 95% CI 0.918-0.979; RR 0.917, 95% CI 0.885 0.950) over the study period. Diabetic ketoacidosis rate showed no significant variation over time. CONCLUSIONS: This study showed a significant improvement in metabolic control in children and adolescents with type 1 diabetes during the past decade and a simultaneous decrease in hypoglycemic events. The improvement was not completely explained by changes in the mode of insulin treatment. Other factors such as improved patient education may have accounted for the observed trend. PMID- 22074727 TI - Incidence of diabetes mellitus and evolution of glucose parameters in growth hormone-deficient subjects during growth hormone replacement therapy: a long-term observational study. AB - OBJECTIVE: Growth hormone (GH) deficiency is associated with insulin resistance and diabetes. The aim of the current study was to determine incidence of diabetes during GH replacement therapy (GHRT) and the effect of GHRT on fasting plasma glucose concentrations and HbA(1c) in adult patients with GH deficiency. RESEARCH DESIGN AND METHODS: A total of 5,143 GH-deficient patients (male 49.9%; mean age +/- SD, 49 +/- 13 years; BMI 29.1 +/- 5.9 kg/m(2)) were analyzed. Mean observation period was 3.9 years (range 0.01-13). Total number of patient-years was 20,106. Observed number of cases (O) was compared with expected number of cases (E). Reference rates were from Sweden, three additional European regions, and one U.S. region. RESULTS: Patients who developed diabetes (n = 523) were older; had higher BMI, waist circumference, triglyceride concentrations, and blood pressure; and had lower HDL-cholesterol concentrations (P < 0.0001) than those who did not develop diabetes. Diabetes incidence was 2.6 per 100 patient years, equal in both sexes, and significantly increased compared with the Swedish reference (O/E = 6.02; P < 0.0001) as well as with the four other populations (O/E = 2.11-5.22). O/E increased with BMI and decreased with duration of GHRT (P < 0.0001). There was no significant association with GH dose (P = 0.74) or IGF-I SDS (P = 0.47). In subjects not developing diabetes, plasma glucose concentrations increased from 84.4 +/- 0.9 mg/dL to 89.5 +/- 0.8 mg/dL (0.70 mg/dL/year) and HbA(1c) increased from 4.74 +/- 0.04% to 5.09 +/- 0.13% (0.036%/year) after 6 years of GHRT. CONCLUSIONS: Diabetes incidence appears to be increased in GH-deficient patients receiving GHRT and exhibiting an adverse risk profile at baseline. Therefore, glucose homeostasis parameters should be monitored carefully in these patients. PMID- 22074728 TI - Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement. AB - BACKGROUND: Osteoarthritis of the knee is a major clinical problem affecting a greater proportion of women than men. Women generally report higher pain intensity at rest and greater perceived functional deficits than men. Women also perform worse than men on function measures such as the 6-minute walk and timed up and go tests. Differences in pain sensitivity, pain during function, psychosocial variables, and physical activity levels are unclear. Further the ability of various biopsychosocial variables to explain physical activity, function and pain is unknown. METHODS: This study examined differences in pain, pain sensitivity, function, psychosocial variables, and physical activity between women and men with knee osteoarthritis (N = 208) immediately prior to total knee arthroplasty. We assessed: (1) pain using self-report measures and a numerical rating scale at rest and during functional tasks, (2) pain sensitivity using quantitative sensory measures, (3) function with self-report measures and specific function tasks (timed walk, maximal active flexion and extension), (4) psychosocial measures (depression, anxiety, catastrophizing, and social support), and (5) physical activity using accelerometry. The ability of these mixed variables to explain physical activity, function and pain was assessed using regression analysis. RESULTS: Our findings showed significant differences on pain intensity, pain sensitivity, and function tasks, but not on psychosocial measures or physical activity. Women had significantly worse pain and more impaired function than men. Their levels of depression, anxiety, pain catastrophizing, social support, and physical activity, however, did not differ significantly. Factors explaining differences in (1) pain during movement (during gait speed test) were pain at rest, knee extension, state anxiety, and pressure pain threshold; (2) function (gait speed test) were sex, age, knee extension, knee flexion opioid medications, pain duration, pain catastrophizing, body mass index (BMI), and heat pain threshold; and (3) physical activity (average metabolic equivalent tasks (METS)/day) were BMI, age, Short-Form 36 (SF-36) Physical Function, Kellgren-Lawrence osteoarthritis grade, depression, and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale. CONCLUSIONS: Women continue to be as physically active as men prior to total knee replacement even though they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on specific functional tasks. PMID- 22074729 TI - An adnexal mass with raised serum beta-HCG: an unusual presentation of ovarian dermoid cyst. PMID- 22074730 TI - [Training of residents in abdominal wall surgery in Spain]. AB - The training of residents in abdominal wall surgery is a fundamental aspect of surgical training, representing globally 20% of its activity. In this paper, we analyze the current state of resident training in this kind of surgery in Spain, taking into account the broad spectrum it covers: general services, specific functional units, ambulatory surgery programs. To do this, based on the specifications of the specialty program, specific data were used from several different sources of direct information and a review of the results obtained by residents in hernia surgery. In general, our residents agree with their training and the recorded results are in line with objectives outlined in the program. However, it would be important to structure their teaching schedules, a rotation period in any specific unit and their involvement in outpatient surgery programs. PMID- 22074731 TI - Lung dendritic cell-epithelial cell crosstalk in Th2 responses to allergens. AB - Dendritic cells (DC) have been shown to be responsible for the initiation and maintenance of adaptive Th2 responses in asthma. It is increasingly clear that DC functions are strongly influenced by crosstalk with neighboring cells like epithelial cells, which can release a number of innate cytokines promoting Th2 responses. Clinically relevant allergens often interfere directly or indirectly with the innate immune functions of airway epithelial cells and DC. A better understanding of these interactions might lead to a better prevention and ultimately to new treatments for asthma. PMID- 22074732 TI - Following up patients with depression after hospital discharge: a mixed methods approach. AB - BACKGROUND: A medication information intervention was delivered to patients with a major depressive episode prior to psychiatric hospital discharge. METHODS: The objective of this study was to explore how patients evolved after hospital discharge and to identify factors influencing this evolution. Using a quasi experimental longitudinal design, the quantitative analysis measured clinical (using the Hospital Anxiety and Depression Scale, the somatic dimension of the Symptom Checklist 90 and recording the number of readmissions) and humanistic (using the Quality of Life Enjoyment and Satisfaction Questionnaire) outcomes of patients via telephone contacts up to one year following discharge. The qualitative analysis was based on the researcher diary, consisting of reports on the telephone outcome assessment of patients with major depression (n = 99). All reports were analyzed using the thematic framework approach. RESULTS: The change in the participants' health status was as diverse as it was at hospital discharge. Participants reported on remissions; changes in mood; relapses; and re admissions (one third of patients). Quantitative data on group level showed low anxiety, depression and somatic scores over time. Three groups of contributing factors were identified: process, individual and environmental factors. Process factors included self caring process, medical care after discharge, resumption of work and managing daily life. Individual factors were symptom control, medication and personality. Environmental factors were material and social environment. Each of them could ameliorate, deteriorate or be neutral to the patient's health state. A mix of factors was observed in individual patients. CONCLUSIONS: After hospital discharge, participants with a major depressive episode evolved in many different ways. Process, individual and environmental factors may influence the participant's health status following hospital discharge. Each of the factors could be positive, neutral or negative for the patient. PMID- 22074733 TI - Self-reported pain severity, quality of life, disability, anxiety and depression in patients classified with 'nociceptive', 'peripheral neuropathic' and 'central sensitisation' pain. The discriminant validity of mechanisms-based classifications of low back (+/-leg) pain. AB - Evidence of validity is required to support the use of mechanisms-based classifications of pain clinically. The purpose of this study was to evaluate the discriminant validity of 'nociceptive' (NP), 'peripheral neuropathic' (PNP) and 'central sensitisation' (CSP) as mechanisms-based classifications of pain in patients with low back (+/-leg) pain by evaluating the extent to which patients classified in this way differ from one another according to health measures associated with various dimensions of pain. This study employed a cross sectional, between-subjects design. Four hundred and sixty-four patients with low back (+/-leg) pain were assessed using a standardised assessment protocol. Clinicians classified each patient's pain using a mechanisms-based classification approach. Patients completed a number of self-report measures associated with pain severity, health-related quality of life, functional disability, anxiety and depression. Discriminant validity was evaluated using a multivariate analysis of variance. There was a statistically significant difference between pain classifications on the combined self-report measures, (p = .001; Pillai's Trace = .33; partial eta squared = .16). Patients classified with CSP (n = 106) reported significantly more severe pain, poorer general health-related quality of life, and greater levels of back pain-related disability, depression and anxiety compared to those classified with PNP (n = 102) and NP (n = 256). A similar pattern was found in patients with PNP compared to NP. Mechanisms-based pain classifications may reflect meaningful differences in attributes underlying the multidimensionality of pain. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain. PMID- 22074734 TI - Muscle activity patterns of the tensor fascia latae and adductor longus for ramp and stair walking. AB - Walking on both outdoor and indoor surfaces requires the ability to negotiate connections between vertical distances, simply known as hills and stairs. Therefore, the purpose of the present study was to evaluate the muscle activity patterns of the TFL and ADL during both hill and stair walking. We hypothesized that TFL and ADL activity during initial swing, initial stance, and late stance of up-ramp and up-stair walking would be greater than level walking. In contrast, we hypothesized that both TFL and ADL activity during initial swing of down-ramp and down-stair walking would be less. We utilized a 15 degrees ramp, a 35 degrees stair set, and for comparison of this steep angle, we also collected data on a 33 degrees ramp. During up-ramp and up-stair walking, TFL and ADL activity during both initial swing and late stance of the up conditions were greater than level walking. For the down conditions, ADL activity during the swing phase of the steep down-ramp was less. Practically, our muscle activity results demonstrate that the hip abductors and hip adductors may provide additional pelvic stability and supplementary thigh acceleration during ramp and stair walking. PMID- 22074735 TI - Excess mortality associated with the 2009 pandemic of influenza A(H1N1) in Hong Kong. AB - Reliable estimates of the burden of 2009 pandemic influenza A(pH1N1) cannot be easily obtained because only a small fraction of infections were confirmed by laboratory tests in a timely manner. In this study we developed a Poisson prediction modelling approach to estimate the excess mortality associated with pH1N1 in 2009 and seasonal influenza in 1998-2008 in the subtropical city Hong Kong. The results suggested that there were 127 all-cause excess deaths associated with pH1N1, including 115 with cardiovascular and respiratory disease, and 22 with pneumonia and influenza. The excess mortality rates associated with pH1N1 were highest in the population aged >=65 years. The mortality burden of influenza during the whole of 2009 was comparable to those in the preceding ten inter-pandemic years. The estimates of excess deaths were more than twofold higher than the reported fatal cases with laboratory-confirmed pH1N1 infection. PMID- 22074736 TI - Impaired ATP-induced coronary blood flow and diminished aortic NTPDase activity precede lesion formation in apolipoprotein E-deficient mice. AB - Intravascular ATP and ADP are important regulators of vascular tone, thrombosis, inflammation, and angiogenesis. This study was undertaken to evaluate the contribution of purinergic signaling to disturbed vasodilation and vascular remodeling during atherosclerosis progression. We used apolipoprotein E-deficient (Apoe(-/-)) mice as an appropriate experimental model for atherosclerosis. Noninvasive transthoracic Doppler echocardiography imaging with adenosine, ATP, and other nucleotides and nonhydrolyzable P2 receptor agonists and antagonists suggests that ATP regulates coronary blood flow in mice through activation of P2Y (most likely, endothelial ATP/UTP-selective P2Y(2)) receptors, rather than via its dephosphorylation to adenosine. Strikingly, compared to age-matched wild-type controls, young (10- to 15-week-old) Apoe(-/-) mice displayed diminished coronary reactivity in response to ATP but not adenosine. The impaired hyperemic response to ATP persisted in older (20- to 30-week-old) Apoe(-/-) mice, which were additionally characterized by mild atherosclerosis (as ascertained by aortic Oil Red O staining) and a systemic increase in plasma ATP and ADP levels. Concurrent thin-layer chromatographic analysis of nucleoside triphosphate diphosphohydrolase (NTPDase) and ecto-5'-nucleotidase/CD73 activities in thoracic aortas, lymph nodes, spleen, and serum revealed that aortic NTPDase was decreased by 40% to 50% in a tissue-specific manner both in young and mature Apoe(-/-) mice. Collectively, disordered purinergic signaling in Apoe(-/-) mice may serve as important prerequisite for impaired blood flow, local accumulation of ATP and ADP at sites of atherogenesis, and eventually, the exacerbation of atherosclerosis. PMID- 22074737 TI - Low-dose-rate, low-dose irradiation delays neurodegeneration in a model of retinitis pigmentosa. AB - The existence of radiation hormesis is controversial. Several stimulatory effects of low-dose (LD) radiation have been reported to date; however, the effects on neural tissue or neurodegeneration remain unknown. Here, we show that LD radiation has a neuroprotective effect in mouse models of retinitis pigmentosa, a hereditary, progressive neurodegenerative disease that leads to blindness. Various LD radiation doses were administered to the eyes in a retinal degeneration mouse model, and their pathological and physiological effects were analyzed. LD gamma radiation in a low-dose-rate (LDR) condition rescues photoreceptor cell apoptosis both morphologically and functionally. The greatest effect was observed in a condition using 650 mGy irradiation and a 26 mGy/minute dose rate. Multiple rounds of irradiation strengthened this neuroprotective effect. A characteristic up-regulation (563%) of antioxidative gene peroxiredoxin 2 (Prdx2) in the LDR-LD-irradiated retina was observed compared to the sham treated control retina. Silencing the Prdx2 using small-interfering RNA administration reduced the LDR-LD rescue effect on the photoreceptors. Our results demonstrate for the first time that LDR-LD irradiation has a biological effect in neural cells of living animals. The results support that radiation exhibits hormesis, and this effect may be applied as a novel therapeutic concept for retinitis pigmentosa and for other progressive neurodegenerative diseases regardless of the mechanism of degeneration involved. PMID- 22074738 TI - BACE2 expression increases in human neurodegenerative disease. AB - beta-Secretase, the rate-limiting enzymatic activity in the production of the amyloid-beta (Abeta) peptide, is a major target of Alzheimer's disease (AD) therapeutics. There are two forms of the enzyme: beta-site Abeta precursor protein cleaving enzyme (BACE) 1 and BACE2. Although BACE1 increases in late stage AD, little is known about BACE2. We conducted a detailed examination of BACE2 in patients with preclinical to late-stage AD, including amnestic mild cognitive impairment, and age-matched controls, cases of frontotemporal dementia, and Down's syndrome. BACE2 protein and enzymatic activity increased as early as preclinical AD and were found in neurons and astrocytes. Although the levels of total BACE2 mRNA were unchanged, the mRNA for BACE2 splice form C (missing exon 7) increased in parallel with BACE2 protein and activity. BACE1 and BACE2 were strongly correlated with each other at all levels, suggesting that their regulatory mechanisms may be largely shared. BACE2 was also elevated in frontotemporal dementia but not in Down's syndrome, even in patients with substantial Abeta deposition. Thus, expression of both forms of beta-secretase are linked and may play a combined role in human neurologic disease. A better understanding of the normal functions of BACE1 and BACE2, and how these change in different disease states, is essential for the future development of AD therapeutics. PMID- 22074740 TI - Antisense knockdown of Kras inhibits fibrosis in a rat model of unilateral ureteric obstruction. AB - Tubulointerstitial fibrosis is the hallmark of chronic kidney disease and is characterized by an increase in the number and activity of interstitial fibroblasts and by excessive matrix deposition. Ras is an intracellular signaling molecule involved in cell proliferation and differentiation. It has recently been implicated in the pathogenesis of renal fibrosis. Of the three different isoforms of Ras (Kirsten, Harvey, and Neural), we previously demonstrated that the Kirsten isoform is key in the control of renal fibroblast proliferation in vitro. In this study, we used gene therapy in the form of antisense oligonucleotides (ASOs) specifically to silence Kras (alias Ki-ras) expression in a rat model of renal fibrosis caused by unilateral ureteric obstruction. We demonstrate that renal Kras expression increases by 70% in this model compared with sham-operated animals and that treatment with ASOs can reduce total renal Kras by >90% to levels well below basal. This silencing is associated with a dramatic inhibition of interstitial fibrosis, a fivefold reduction in alpha-smooth muscle actin expression, and a 2.4-fold reduction in collagen I deposition. This inhibition was observed despite histologic evidence of marked interstitial inflammation. These findings demonstrate that silencing Kras expression can markedly inhibit renal fibrosis. This strategy should be considered as a new potential therapeutic avenue. PMID- 22074739 TI - Alterations in nuclear pore architecture allow cancer cell entry into or exit from drug-resistant dormancy. AB - Phenotypic diversity arises in tumors just as it does in developing organisms, and tumor recurrence frequently manifests from the selective survival of divergent drug-resistant cells. Although the expanding tumor cell population may be successfully targeted, drug-resistant cells may persist and sustain the tumor or enter dormancy before igniting a future relapse. Herein, we show that partial knockdown of nucleoporin p62 (NUP62) by small-interfering RNA confers cisplatin resistance to cultured high-grade ovarian carcinoma cells. Treatment with NUP62 small-interfering RNA and cisplatin leaves resistant cells in a state of dormancy; some dormant cells can be induced to proliferate by transient induction of NUP62 expression from an ectopic expression construct. In addition to suggesting functional links between nuclear pore complex architecture and cancer cell survival, the culture system provides a novel experimental window into the dynamics of tumor cell drug resistance and dormancy. PMID- 22074741 TI - [Third molar and mandibular canal: selection of radiographic techniques]. AB - Injury of the inferior alveolar nerve during extraction of mandibular third molar is a well recognized, but uncommon, serious complication. It has a serious impact on oral function and its psychological impact on the patient is great. To prevent this complication, several studies have been conducted to identify the high-risk radiological signs associated with intimate anatomic relationships between third molar and infra-alveolar nerve and thereby establish a unified process of radiological exploration. In this paper, the authors present a review of the literature of the recent studies involving radiological exploration of the relation of the third molar with the mandibular canal. PMID- 22074742 TI - Optimization on preparation condition of epimedium polysaccharide liposome and evaluation of its adjuvant activity. AB - The aim of this strategy was to investigate whether the adjuvant activity of epimedium polysaccharide (EPS) could be further enhanced after encapsulated with liposome. In preparation of EPS liposome (EPSL) test, an orthogonal L(9) (3(4)) test design was used to optimize the preparation condition of EPSL. In adjuvant activity test, 350 14-day-old chickens were randomly assigned to 7 groups and vaccinated with Newcastle disease (ND) vaccine. Simultaneously, the chickens in experimental groups were injected with EPSL at three doses, EPS and blank liposome, respectively. The activity of lymphocytes proliferation, titer of serum antibody and concentrations of cytokines were determined. Results showed that the optimal preparation condition of EPSL was that ratio of drug to lipid, ratio of soybean phospholipid to cholesterol, ultrasonic time, and water bath temperature were 1:30, 4:1, 10 min and 40 degrees C, respectively. EPSL could significantly enhance the immune response of ND vaccine and promote cytokines secretion, and its high dose possessed the best efficacy. These findings indicated that liposome encapsulation could significantly improve the adjuvant activity of EPS. PMID- 22074743 TI - Wireless remote monitoring of reconstructed 12-lead ECGs after ablation for atrial fibrillation using a hand-held device. AB - OBJECTIVE: Atrial fibrillation (AF) surveillance using a wireless handheld monitor capable of 12-lead electrocardiogram reconstruction was performed, and arrhythmia detection rate was compared with serial Holter monitoring. METHODS: Twenty-five patients were monitored after an AF ablation procedure using the hand held monitor for 2 months immediately after and then for 1 month approximately 6 months postablation. All patients underwent 12-lead 24-hour Holter monitoring at 1, 2, and 6 months postablation. RESULTS: During months 1-2, 425 of 2942 hand held monitor transmissions from 21 of 25 patients showed AF/atrial flutter (Afl). The frequency of detected arrhythmias decreased by month 6 to 85/1128 (P < .01) in 15 of 23 patients. Holter monitoring diagnosed AF/Afl in 8 of 25 and 7 of 23 patients at months 1-2 and month 6, respectively (P < .01 compared with wireless hand-held monitor). Af/Afl diagnosis by wireless monitoring preceded Holter detection by an average of 24 days. CONCLUSIONS: Wireless monitoring with 12-lead electrocardiogram reconstruction demonstrated reliable AF/Afl detection that was more sensitive than serial 12-lead 24-hour Holter monitoring. PMID- 22074745 TI - Role of the vectorcardiogram-derived spatial QRS-T angle in diagnosing left ventricular hypertrophy. AB - INTRODUCTION: Current criteria for electrocardiographic (ECG) diagnosis of left ventricular hypertrophy (LVH) have a low diagnostic accuracy. Addition of demographic, anthropomorphic, and additional ECG variables may improve accuracy. As hypertrophy affects action potential morphology and intraventricular conduction, QRS prolongation and T-wave morphology may occur and become manifest in the vectorcardiographic variables spatial QRS-T angle (SA) and spatial ventricular gradient. In this study, we attempted to improve the diagnostic accuracy for LVH by using a combination of demographic, anthropomorphic, ECG, and vectorcardiographic variables. METHODS: The study group (n = 196) was divided in 4 subgroups with, on one hand, echocardiographically diagnosed LVH or a normal echocardiogram and, on the other hand, with any of the conventional ECG signs for LVH or with normal ECGs. Each subgroup was randomly split into halves, yielding 2 equally-sized (n = 98) data sets A and B. Age, sex, height, weight, body mass index, body surface area (BSA), frontal QRS axis, QRS duration, QT duration, maximal QRS vector magnitude, SA, and ventricular gradient magnitude and orientation were univariate studied by receiver operating characteristic analysis and were used to build a stepwise linear discriminant model using P < .05 as entry and P > .10 as removal criterion. The discriminant model was built in set A (model A) and tested on set B. Stability checks were done by building a discriminant model on set B and testing on set A and by cross-validation analysis in the complete study group. RESULTS: The discriminant model equation was D = 5.130 * BSA - 0.014 * SA - 8.74, wherein D greater than or equal to 0 predicts a normal echocardiogram and D less than 0 predicts LVH. The diagnostic accuracy (79%) was better than the diagnostic accuracy of conventional ECG criteria for LVH (57%). CONCLUSION: The combination of BSA and SA yields a diagnostic accuracy of LVH that is superior to that of the conventional ECG criteria. PMID- 22074744 TI - Outcome after implantable cardioverter-defibrillator in patients with Brugada syndrome: the Gulf Brugada syndrome registry. AB - BACKGROUND AND OBJECTIVE: Among patients with Brugada syndrome (BS) and aborted cardiac arrest, syncope, or inducible ventricular fibrillation at electrophysiologic study (EPS), the only currently recommended therapy is an implantable cardioverter-defibrillator (ICD), but these are not without complications. We assessed the total number of shocks (appropriate and inappropriate) and complications related to ICD in patients with BS. METHODS AND RESULTS: Twenty-five patients implanted with ICD for BS in 6 Gulf centers between January 1, 2002, and December 31, 2010, were reviewed. Implantable cardioverter defibrillator indication was based on aborted cardiac arrest (24%), syncope (56%), or in asymptomatic patients with positive EPS (20%). During a follow-up of 41.2 +/- 17.6 months, 3 patients (all with prior cardiac arrest) had appropriate device therapy. Four patients developed complications; 3 of them had inappropriate shocks. CONCLUSION: In our cohort, appropriate device therapy was limited to cardiac arrest survivors, whereas none of those with syncope and/or positive EPS had arrhythmias. Overall complication rate was relatively high, including inappropriate ICD shocks. PMID- 22074746 TI - Triplex tetra-primer ARMS-PCR method for the simultaneous detection of MTHFR c.677C>T and c.1298A>C, and MTRR c.66A>G polymorphisms of the folate-homocysteine metabolic pathway. AB - The folate-homocysteine metabolic pathway was shown to play an important role in several diseases such as cancers, cardiovascular diseases, and neurodegenerative diseases. The c.677C>T and c.1298A>C polymorphisms of the Methylenetetrahydrofolate reductase (MTHFR) gene, and c.66A>G of the Methionine synthase reductase (MTRR) gene are the most commonly investigated polymorphisms in the folate-homocysteine metabolic pathway. The currently used methods for the detection of the three polymorphisms are either slow and laborious or extremely expensive. In this paper, a new highly optimized method for the simultaneous detection of the three single nucleotide polymorphisms is described. The proposed method utilizes 12 primers in a single PCR reaction to detect the three polymorphisms simultaneously based on the principle of tetra-primer ARMS-PCR (also known as PCR-CTPP). The proposed method offers extremely fast, economical, and simple detection. Validation by PCR-RFLP showed 100% concordance in genotype assignment. The proposed method was successfully applied to a sample of the Syrian population (n=126), which was not previously genotyped for any of the three SNPs. The variant allele frequencies were found to be 31, 29, and 43% for the c.677C>T, c.1298A>C, and c.66A>G polymorphisms, respectively. The proposed method is the first to detect three SNPs in a single PCR reaction based on tetra primer ARMS-PCR or PCR-CTPP. We suggest that the use of Betaine may play an important role in multiplex tetra-primer ARMS-PCR or PCR-CTPP based on its potential capacity to close the gap in melting temperature between different primers. PMID- 22074747 TI - The OPPERA study: Act One. PMID- 22074748 TI - Summary of findings from the OPPERA baseline case-control study: implications and future directions. PMID- 22074749 TI - Study methods, recruitment, sociodemographic findings, and demographic representativeness in the OPPERA study. AB - This paper describes methods used in the project "Orofacial Pain Prospective Evaluation and Risk Assessment" (OPPERA) and evaluates sociodemographic characteristics associated with temporomandibular disorders (TMD) in the OPPERA case-control study. Representativeness was investigated by comparing sociodemographic profiles of OPPERA participants with population census profiles of counties near study sites and by comparing age and gender associations with TMD in OPPERA and the 2007 to 2009 US National Health Interview Survey. Volunteers aged 18 to 44 years were recruited at 4 US study sites: 3,263 people without TMD were enrolled into the prospective cohort study; 1,633 of them were selected as controls for the baseline case-control study. Cases were 185 volunteers with examiner-classified TMD. Distributions of some demographic characteristics among OPPERA participants differed from census profiles, although there was less difference in socioeconomic profiles. Odds of TMD was associated with greater age in this 18 to 44 year range; females had 3 times the odds of TMD as males; and relative to non-Hispanic-Whites, other racial groups had one-fifth the odds of TMD. Age and gender associations with chronic TMD were strikingly similar to associations observed in the US population. Assessments of representativeness in this demographically diverse group of community volunteers suggest that OPPERA case-control findings have good internal validity. PERSPECTIVE: Demographic associations with TMD were consistent with population benchmarks and with other studies, suggesting broad applicability of these OPPERA findings. Greater occurrence of TMD in non-Hispanic-Whites than in other racial/ethnic groups and the lack of a socioeconomic gradient contradicts the disparities seen in many other health conditions. PMID- 22074750 TI - Clinical findings and pain symptoms as potential risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case-control study. AB - Clinical characteristics might be associated with temporomandibular disorders (TMD) because they are antecedent risk factors that increase the likelihood of a healthy person developing the condition or because they represent signs or symptoms of either subclinical or overt TMD. In this baseline case-control study of the multisite Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project, 1,633 controls and 185 cases with chronic, painful TMD completed questionnaires and received clinical examinations. Odds ratios measuring association between each clinical factor and TMD were computed, with adjustment for study-site as well as age, sex, and race/ethnicity. Compared to controls, TMD cases reported more trauma, greater parafunction, more headaches and other pain disorders, more functional limitation in using the jaw, more nonpain symptoms in the facial area, more temporomandibular joint noises and jaw locking, more neural or sensory medical conditions, and worse overall medical status. They also exhibited on examination reduced jaw mobility, more joint noises, and a greater number of painful masticatory, cervical, and body muscles upon palpation. The results indicated that TMD cases differ substantially from controls across almost all variables assessed. Future analyses of follow-up data will determine whether these clinical characteristics predict increased risk for developing first-onset pain-related TMD PERSPECTIVE: Clinical findings from OPPERA's baseline case-control study indicate significant differences between chronic TMD cases and controls with respect to trauma history, parafunction, other pain disorders, health status, and clinical examination data. Future analyses will examine their contribution to TMD onset. PMID- 22074751 TI - Orofacial pain prospective evaluation and risk assessment study--the OPPERA study. PMID- 22074752 TI - Potential psychosocial risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case-control study. AB - Case-control studies have consistently associated psychosocial factors with chronic pain in general, and with temporomandibular disorders (TMD) specifically. Moreover, a handful of prospective studies suggest that preexisting psychosocial characteristics represent risk factors for new onset TMD. The current study presents psychosocial findings from the baseline case-control study of the Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) cooperative agreement. For this study, 1,633 TMD-free controls and 185 TMD cases completed a battery of psychosocial instruments assessing general psychosocial adjustment and personality, affective distress, psychosocial stress, somatic awareness, and pain coping and catastrophizing. In bivariate and demographically adjusted analyses, odds of TMD were associated with higher levels of psychosocial symptoms, affective distress, somatic awareness, and pain catastrophizing. Among controls, significant gender and ethnic group differences in psychosocial measures were observed, consistent with previous findings. Principal component analysis was undertaken to identify latent constructs revealing 4 components: stress and negative affectivity, global psychosocial symptoms, passive pain coping, and active pain coping. These findings provide further evidence of associations between psychosocial factors and TMD. Future prospective analyses in the OPPERA cohort will determine if the premorbid presence of these psychosocial factors predicts increased risk for developing new onset TMD. PERSPECTIVE: This article reports baseline psychosocial findings from the OPPERA Study, a large prospective cohort study designed to discover causal determinants of TMD pain. Findings indicate significant differences between TMD cases and TMD-free controls across multiple psychosocial constructs, and future analyses will determine whether these psychosocial factors increase risk for new onset TMD. PMID- 22074753 TI - Pain sensitivity risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case control study. AB - Many studies report that people with temporomandibular disorders (TMD) are more sensitive to experimental pain stimuli than TMD-free controls. Such differences in sensitivity are observed in remote body sites as well as in the orofacial region, suggesting a generalized upregulation of nociceptive processing in TMD cases. This large case-control study of 185 adults with TMD and 1,633 TMD-free controls measured sensitivity to painful pressure, mechanical cutaneous, and heat stimuli, using multiple testing protocols. Based on an unprecedented 36 experimental pain measures, 28 showed statistically significantly greater pain sensitivity in TMD cases than controls. The largest effects were seen for pressure pain thresholds at multiple body sites and cutaneous mechanical pain threshold. The other mechanical cutaneous pain measures and many of the heat pain measures showed significant differences, but with lesser effect sizes. Principal component analysis (PCA) of the pain measures derived from 1,633 controls identified 5 components labeled: 1) heat pain ratings; 2) heat pain aftersensations and tolerance; 3) mechanical cutaneous pain sensitivity; 4) pressure pain thresholds; and 5) heat pain temporal summation. These results demonstrate that compared to TMD-free controls, chronic TMD cases are more sensitive to many experimental noxious stimuli at extracranial body sites, and provide for the first time the ability to directly compare the case-control effect sizes of a wide range of pain sensitivity measures. PERSPECTIVE: This article describes experimental pain sensitivity differences between a large sample of people with chronic TMD and non-TMD controls, using multiple stimulus modalities and measures. Variability in the magnitude and consistency of case control differences highlight the need to consider multiple testing measures to adequately assess pain processing alterations in chronic pain conditions. PMID- 22074754 TI - Potential autonomic risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case-control study. AB - Several case-control studies have been conducted that examine the association between autonomic variables and persistent pain conditions; however, there is a surprising dearth of published studies in this area that have focused on temporomandibular disorders (TMD). The current study presents autonomic findings from the baseline case-control study of the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) cooperative agreement. Measures of arterial blood pressure, heart rate, heart rate variability, and indirect measures of baroreflex sensitivity were assessed at rest and in response to a physical (orthostatic) and psychological (Stroop) stressors in 1,633 TMD-free controls and 185 TMD cases. In bivariate and demographically adjusted analyses, greater odds of TMD case status were associated with elevated heart rates, reduced heart rate variability, and reduced surrogate measures of baroreflex sensitivity across all experimental procedures. Principal component analysis was undertaken to identify latent constructs revealing 5 components. These findings provide evidence of associations between autonomic factors and TMD. Future prospective analyses in the OPPERA cohort will determine if the presence of these autonomic factors predicts increased risk for developing new onset TMD. PERSPECTIVE: This article reports autonomic findings from the OPPERA Study, a large prospective cohort study designed to discover causal determinants of TMD pain. Findings indicate statistically significant differences between TMD cases and controls across multiple autonomic constructs at rest and during both physical and psychologically challenging conditions. Future analyses will determine whether these autonomic factors increase risk for new onset TMD. PMID- 22074756 TI - Children with behavioral, non-behavioral, and multiple disabilities, and the risk of out-of-home placement disruption. AB - OBJECTIVE: This study examined the relative risk of placement disruption for 3-10 year-old children placed in out-of-home care based on the biological relatedness of the placement caregiver and child disability status: no disability, a non behavioral disability only, a behavioral disability only, or both a non behavioral and behavioral disability. METHODS: Data were used from the baseline and 36 month follow-up of the National Survey of Child and Adolescent Well-Being, a national probability study of children investigated for child abuse and neglect in the United States. Disability status was derived using several different nationally-normed measures of language development, daily-living skills, social skills, and behavioral problems. RESULTS: Around 1 in 4 children placed in out-of home care experienced a disruption. Placement with kin decreased the likelihood of disruption for a majority of children, and children with different types of disabilities were no more or less likely to disrupt in kinship care compared to children with no disability. Older children with a behavioral disability only or both a non-behavioral and behavioral disability were more likely to disrupt compared to younger regardless of placement. CONCLUSION: The study findings suggest that maltreated children placed with kin will be afforded the same stability provided to children without a disability. PMID- 22074755 TI - Potential genetic risk factors for chronic TMD: genetic associations from the OPPERA case control study. AB - Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1,442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3,295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously reported associations between TMD and 2 genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD, and they identify potential targets for therapeutic intervention. PERSPECTIVE: Genetic risk factors for TMD pain were explored in the case-control component of the OPPERA cooperative agreement, a large population-based prospective cohort study. Over 350 candidate pain genes were assessed using a candidate gene panel, with several genes displaying preliminary evidence for association with TMD status. PMID- 22074757 TI - Munchausen by proxy by Internet. PMID- 22074758 TI - Malicious use of nonpharmaceuticals in children. AB - OBJECTIVE: The objective of this study was to describe malicious nonpharmaceutical exposures in children reported to US poison centers. METHODS: We performed a retrospective study of all nonpharmaceutical exposures involving children 7 years old reported to the US National Poison Data System (NPDS) from 2000 to 2008 for which the reason for exposure was coded as "malicious". The American Association of Poison Control Centers definition and categorization of nonpharmaceuticals was used. Data collected for each case included age, gender, month and year of the exposure, the exposed substance or substances, intent, and poison center outcome designation. Fatality abstracts (summaries of the facts reported to the poison center) were reviewed. RESULTS: Out of approximately 21.4 million exposures reported to NPDS during the study period, 4,053 cases involving 4,232 nonpharmaceuticals were identified. The mean number of cases per year was 450 (range 409-546) with no linear annual trend (p=0.28). The median age was 3 years (1.5, 5) with boys constituting 57%. 4.5% of the cases resulted in moderate or worse outcomes in which the outcome was known. The most commonly reported major categories were household cleaning substances (23%), cosmetics/personal care products (13%), pesticides (8%), other/unknown nondrug substances (6%), foreign bodies/toys/miscellaneous (5%), alcohols (5%), hydrocarbons (4%), lacrimators (4%), chemicals (4%), and deodorizers (3%). Four children died and 18 others had lifethreatening injuries. Among these 22 children, cleaning substances (7) were the most common major category followed by chemicals (4), alcohols (3), fumes/gases/vapors (2) and six other categories with 1 each. In the only case where the presence or absence of associated physical injuries was described, the child had multiple injuries consistent with physical abuse. CONCLUSION: Malicious administration of nonpharmaceuticals is an important component of child maltreatment with cases being reported consistently to poison centers. PRACTICAL IMPLICATIONS: Clinicians should consider the possibility of child abuse when presented with these exposures. PMID- 22074759 TI - Self reported awareness of child maltreatment among school professionals in Saudi Arabia: impact of CRC ratification. AB - OBJECTIVES: The Convention on the Rights of the Child (CRC) was ratified by Saudi Arabia 15 years ago; yet addressing the issue of child maltreatment only began in more recent years. School professionals play a significant role in children's lives, as they spend a great deal of time with them and are hence essential to protecting and identifying those in danger or at risk. The objective of this study is to identify school professional's awareness of child maltreatment and the existing national policies and procedures to examine the extent of efforts made in Saudi Arabia and to activate the roles of schools and school professionals in protecting children from violence and implementation of Article 19 of the CRC. METHODS: This was a cross-sectional study, where school professionals from randomly selected schools throughout the country were invited to participate in a self-administered questionnaire. RESULTS: A total of 3,777 school professionals participated in the study. Fifty-five percent of professionals had at least 10 years of work experience. A low-level of awareness of child maltreatment was found in about 1/3 of school professionals. Only 1.9% of school professionals had ever attended any sort of specific training on child maltreatment, though 69.3% of those who had not, were willing to attend future training. With regards to awareness of CRC Article 19 or policies and procedures addressing child maltreatment, only 22% reported being aware of it. CONCLUSION: The majority of school professionals in Saudi Arabia have a low-intermediate level of awareness of child maltreatment, ratification of CRC, and related national policies and procedures, yet most are willing to attend training programs on this subject matter. Efforts need to be made in the country to fill this gap. PMID- 22074761 TI - Reporting and grading of complications after urologic surgical procedures: an ad hoc EAU guidelines panel assessment and recommendations. AB - CONTEXT: The incidence of postoperative complications is still the most frequently used surrogate marker of quality in surgery, but no standard guidelines or criteria exist for reporting surgical complications in the area of urology. OBJECTIVE: To review the available reporting systems used for urologic surgical complications, to establish a possible change in attitude towards reporting of complications using standardised systems, to assess systematically the Clavien-Dindo system when used for the reporting of complications related to urologic surgical procedures, to identify shortcomings in reporting complications, and to propose recommendations for the development and implementation of future reporting systems that are focused on patient-centred outcomes. EVIDENCE ACQUISITION: Standardised systems for reporting and classification of surgical complications were identified through a systematic review of the literature. To establish a possible change in attitude towards reporting of complications related to urologic procedures, we performed a systematic literature search of all papers reporting complications after urologic surgery published in European Urology, Journal of Urology, Urology, BJU International, and World Journal of Urology in 1999-2000 and 2009-2010. Data identification for the systematic assessment of the Clavien-Dindo system currently used for the reporting of complications related to urologic surgical interventions involved a Medline/Embase search and the search engines of individual urologic journals and publishers using Clavien, urology, and complications as keywords. All selected papers were full-text retrieved and assessed; analysis was done based on structured forms. EVIDENCE SYNTHESIS: The systematic review of the literature for standardised systems used for reporting and classification of surgical complications revealed five such systems. As far as the attitude of urologists towards reporting of complications, a shift could be seen in the number of studies using most of the Martin criteria, as well as in the number of studies using either standardised criteria or the Clavien-Dindo system. The latter system was not properly used in 72 papers (35.3%). CONCLUSIONS: Uniformed reporting of complications after urologic procedures will aid all those involved in patient care and scientific publishing (authors, reviewers, and editors). It will also contribute to the improvement of the scientific quality of papers published in the field of urologic surgery. When reporting the outcomes of urologic procedures, the committee proposes a series of quality criteria. PMID- 22074760 TI - Influence of RNA labeling on expression profiling of microRNAs. AB - Although a number of technical parameters are now being examined to optimize microRNA profiling experiments, it is unknown whether reagent or component changes to the labeling step affect starting RNA requirements or microarray performance. Human brain/lung samples were each labeled in duplicate, at 1.0, 0.5, 0.2, and 0.1 MUg of total RNA, by means of two kits that use the same labeling procedure but differ in the reagent composition used to label microRNAs. Statistical measures of reliability and validity were used to evaluate microarray data. Cross-platform confirmation was accomplished using TaqMan microRNA assays. Synthetic microRNA spike-in experiments were also performed to establish the microarray signal dynamic range using the ligation-modified kit. Technical replicate correlations of signal intensity values were high using both kits, but improved with the ligation-modified assay. The drop in detection call sensitivity and miRNA gene list correlations, when using reduced amounts of standard-labeled RNA, was considerably improved with the ligation-modified kit. Microarray signal dynamic range was found to be linear across three orders of magnitude from 4.88 to 5000 attomoles. Thus, optimization of the microRNA labeling reagent can result in at least a 10-fold decrease in microarray total RNA requirements with little compromise to data quality. Clinical investigations bottlenecked by the amount of starting material may use a ligation mix modification strategy to reduce total RNA requirements. PMID- 22074762 TI - Evaluating the effect of various background correction methods regarding noise reduction, in two-channel microarray data. AB - In this work, two novel background correction (BC) methods, along with several commonly used ones, are evaluated regarding noise reduction in eleven two-channel self-versus-self (SVS) hybridizations. The evaluation of each BC method is investigated under the use of four statistical criteria combined into a single measure, the polygon area measure. Overall, our proposed BC approaches perform very well in terms of the proposed measure for most of the cases and provide an improved effect regarding technical noise reduction. PMID- 22074763 TI - Ant colony optimization-based feature selection method for surface electromyography signals classification. AB - This paper presented a new ant colony optimization (ACO) feature selection method to classify hand motion surface electromyography (sEMG) signals. The multiple channels of sEMG recordings make the dimensionality of sEMG feature grow dramatically. It is known that the informative feature subset with small size is a precondition for the accurate and computationally efficient classification strategy. Therefore, this study proposed an ACO based feature selection scheme using the heuristic information measured by the minimum redundancy maximum relevance criterion (ACO-mRMR). The experiments were conducted on ten subjects with eight upper limb motions. Two feature sets, i.e., time domain features combined with autoregressive model coefficients (TDAR) and wavelet transform (WT) features, were extracted from the recorded sEMG signals. The average classification accuracies of using ACO reduced TDAR and WT features were 95.45+/ 2.2% and 96.08+/-3.3%, respectively. The principal component analysis (PCA) was also conducted on the same data sets for comparison. The average classification accuracies of using PCA reduced TDAR and WT features were 91.51+/-4.9% and 89.87+/-4.4%, respectively. The results demonstrated that the proposed ACO-mRMR based feature selection method can achieve considerably high classification rates in sEMG motion classification task and be applicable to other biomedical signals pattern analysis. PMID- 22074764 TI - Reasons parents exempt children from receiving immunizations. AB - School nurses are on the front lines of educational efforts to promote childhood vaccinations. However, some parents still choose to exempt their children from receiving vaccinations for personal reasons. Studying the beliefs of parents who exempt vaccinations allows health care workers, including school nurses, to better understand parental concerns which may, in turn, help prepare school nurses for effective communication with these parents. The objective of the study was to explore personal beliefs of parents living in Utah, who exempted their children from receiving vaccinations. A cross-sectional, descriptive design was implemented. Data were collected from a convenience sample of 287 parents responding to an open-ended question about why they exempted their children from receiving at least one vaccination. The qualitative data included parental comments, concerns, or suggestions regarding childhood vaccinations. Five categories were identified regarding reasons for personal exemptions: parental perceptions, health care systems issues, chronic disease concerns, immune system concerns, adverse reaction concerns and other reasons not classified. The number of parents refusing childhood vaccinations remains relatively low; however, despite public health efforts, the percentage increases each year. PMID- 22074765 TI - Oral health patterns among schoolchildren in Mafraq Governorate, Jordan. AB - Little is known about the oral hygiene patterns among schoolchildren in Jordan. A school-based cross-sectional study was performed from January to March 2010. A simple random sampling method was used. Each student participant completed a detailed questionnaire regarding oral hygiene habits. Data were coded and analyzed using SPSS software version 16. The chi-square was used, odds ratio (OR) and the 95% confidence limits (Cl) for gum bleeding were estimated. The results showed that nearly one fourth of the children indicating that they brush their teeth twice or more daily (regular pattern). Furthermore, 17% of the schoolchildren never brush their teeth at all. There is a higher proportion, 22.1%, of rural children that never brush their teeth compared to 14.6% of the urban students. Dental flossing among primary schoolchildren in Mafraq Governorate is very rare: 97.2% of the children stated that they had never used dental floss in their life. Furthermore, one fourth of the schoolchildren did not have a tooth brush. While 15.0% of them have a shared toothbrush with their families. The findings of this study indicate that oral health habits in Mafraq Governorate are poor and need to be improved. Based upon these finding, community oriented oral health programs should be established. PMID- 22074766 TI - Motives for smoking in movies affect future smoking risk in middle school students: an experimental investigation. AB - BACKGROUND: Exposure to smoking in movies has been linked to adolescent smoking uptake. However, beyond linking amount of exposure to smoking in movies with adolescent smoking, whether the way that smoking is portrayed in movies matters for influencing adolescent smoking has not been investigated. This study experimentally examined how motivation for smoking depicted in movies affects self-reported future smoking risk (a composite measure with items that assess smoking refusal self-efficacy and smoking intentions) among early adolescents. METHODS: A randomized laboratory experiment was used. Adolescents were exposed to movie scenes depicting one of three movie smoking motives: social smoking motive (characters smoked to facilitate social interaction); relaxation smoking motive (characters smoked to relax); or no smoking motive (characters smoked with no apparent motive, i.e., in neutral contexts and/or with neutral affect). Responses to these movie scenes were contrasted (within subjects) to participants' responses to control movie scenes in which no smoking was present; these control scenes matched to the smoking scenes with the same characters in similar situations but where no smoking was present. A total of 358 adolescents, aged 11 14 years, participated. RESULTS: Compared with participants exposed to movie scenes depicting characters smoking with no clear motive, adolescents exposed to movie scenes depicting characters smoking for social motives and adolescents exposed to movie scenes depicting characters smoking for relaxation motives had significantly greater chances of having increases in their future smoking risk. CONCLUSIONS: Exposure to movies that portray smoking motives places adolescents at particular risk for future smoking. PMID- 22074767 TI - Proteome analysis of bronchoalveolar lavage in pulmonary langerhans cell histiocytosis. AB - BACKGROUND: Pulmonary Langerhans-cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by clusters of Langerhans cells, organized in granulomas, in the walls of distal bronchioles. It is a diffuse lung disease related to tobacco smoking but otherwise of unknown etiopathogenesis. METHODS: In this study we used a proteomic approach to analyze BAL protein composition of patients with PLCH and of healthy smoker and non-smoker controls to obtain insights into the pathogenetic mechanisms of the disease, to study the effect of cigarette smoking on susceptibility to PLCH and to identify potential new biomarkers. RESULTS: Two-dimensional electrophoresis and image analysis revealed proteins that were differently expressed (quantitatively and qualitatively) in the three groups of subjects. The proteins were identified by mass spectrometry and have various functions (antioxidant, proinflammatory, antiprotease) and origins (plasma, locally produced, etc.). Many, such as protease inhibitors (human serpin B3) and antioxidant proteins (glutathione peroxidase and thioredoxin) are already linked to PLCH pathogenesis, whereas other proteins have never been associated with the disease. Interestingly, numerous proteolytic fragments of plasma proteins (including kininogen-1 N fragments and haptoglobin) were also identified and suggest increased proteolytic activity in this inflammatory lung disease. Differences in protein expression were found between the three groups and confirmed by Principal Component Analysis (PCA). CONCLUSION: Analysis of BAL proteomes of PLCH patients and of smoker and non-smoker controls also proved to be useful for researching the pathogenetic mechanisms and for identifying biomarkers of this rare diffuse lung disease. PMID- 22074768 TI - Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probe. AB - Positron emission tomography (PET) reporter gene imaging can be used to non invasively monitor cell-based therapies. Therapeutic cells engineered to express a PET reporter gene (PRG) specifically accumulate a PET reporter probe (PRP) and can be detected by PET imaging. Expanding the utility of this technology requires the development of new non-immunogenic PRGs. Here we describe a new PRG-PRP system that employs, as the PRG, a mutated form of human thymidine kinase 2 (TK2) and 2'-deoxy-2'-18F-5-methyl-1-beta-L-arabinofuranosyluracil (L-18F-FMAU) as the PRP. We identified L-18F-FMAU as a candidate PRP and determined its biodistribution in mice and humans. Using structure-guided enzyme engineering, we generated a TK2 double mutant (TK2-N93D/L109F) that efficiently phosphorylates L 18F-FMAU. The N93D/L109F TK2 mutant has lower activity for the endogenous nucleosides thymidine and deoxycytidine than wild type TK2, and its ectopic expression in therapeutic cells is not expected to alter nucleotide metabolism. Imaging studies in mice indicate that the sensitivity of the new human TK2 N93D/L109F PRG is comparable with that of a widely used PRG based on the herpes simplex virus 1 thymidine kinase. These findings suggest that the TK2 N93D/L109F/L-18F-FMAU PRG-PRP system warrants further evaluation in preclinical and clinical applications of cell-based therapies. PMID- 22074769 TI - Phenacetin pharmacokinetics in CYP1A2-deficient beagle dogs. AB - Phenacetin is widely used as an in vitro probe to measure CYP1A2 activity across species. To investigate whether phenacetin can be used as an in vivo probe substrate to phenotype CYP1A2 activity in dogs, beagle dogs previously genotyped for a single nucleotide polymorphism that yields an inactive CYP1A2 protein were selected and placed into one of three groups: CC (wild-type), CT (heterozygous), or TT (homozygous mutants). The dogs were dosed with phenacetin orally at 5 and 15 mg/kg and intravenously at 15 mg/kg. Plasma samples were analyzed by liquid chromatography-tandem mass spectrometry, and phenacetin and its primary metabolite, acetaminophen, were monitored. After intravenous dosing, all groups showed similar exposure of phenacetin irrespective of genotype. After oral dosing at 15 mg/kg, the exposure of phenacetin in CC and CT dogs was similar, but phenacetin exposure was 2-fold greater in TT dogs. Exposure of the metabolite, acetaminophen, was similar in all groups; however, the mean acetaminophen/phenacetin ratio in TT dogs was 1.7 times less than that observed in CC dogs. Similar trends between the groups of dogs with respect to phenacetin exposure were also observed after a lower 5 mg/kg p.o. dose of phenacetin; however, a proportionally greater amount of acetaminophen was generated. Although oral exposure of phenacetin was 2-fold higher and acetaminophen exposure was 2 fold lower in CYP1A2-deficient (TT) dogs, these results were considered modest and suggest that phenacetin is not a selective or robust in vivo probe to measure CYP1A2 enzyme activity in the dog. PMID- 22074770 TI - When four principles are too many: bloodgate, integrity and an action-guiding model of ethical decision making in clinical practice. AB - Medical ethical analysis remains dominated by the principlist account first proposed by Beauchamp and Childress. This paper argues that the principlist model is unreflective of how ethical decisions are taken in clinical practice. Two kinds of medical ethical decisions are distinguished: biosocial ethics and clinical ethics. It is argued that principlism is an inappropriate model for clinical ethics as it is neither sufficiently action-guiding nor does it emphasise the professional integrity of the clinician. An alternative model is proposed for decision making in the realm of clinical ethics. PMID- 22074771 TI - Genetic enhancement, post-persons and moral status: a reply to Buchanan. AB - Responding to several leading ideas from a paper by Allen Buchanan, the present essay explores the implications of genetic enhancement for moral status. Contrary to doubts expressed by Buchanan, I argue that genetic enhancement could lead to the existence of beings so superior to contemporary human beings that we might aptly describe them as post-persons. If such post-persons emerged, how should we understand their moral status in relation to ours? The answer depends in part on which of two general models of moral status--one based on respect and one based on interests--is more adequate. Buchanan tentatively argues that a respect-based model is preferable. I challenge Buchanan's view, along these lines: If we embrace a respect-based model of moral status featuring a threshold that divides persons, who are thought to have full and equal moral status, from sentient nonpersons, thought to have less moral status, then we should acknowledge a second threshold and a level of moral status higher than ours. A better option, I tentatively suggest, is to drop the idea of levels of moral status, accept that all sentient beings have moral status, and allow that some differences in interests and capacities justify some significant differences in how we should treat beings of different kinds. PMID- 22074772 TI - Discovery of "essential receptor" on red blood cells raises hope of effective malaria vaccine. PMID- 22074773 TI - Population based screening in Scotland reduces bowel cancer deaths. PMID- 22074774 TI - Mississippi voters decide fertilised eggs are not people. PMID- 22074775 TI - Soil warming alters seed-bank responses across the geographic range of freshwater Taxodium distichum (Cupressaceae) swamps. AB - PREMISE OF THE STUDY: Climate warming is predicted to have far-reaching effects on the distribution of species, but those effects may depend on the flexibility of regenerating species in responding to climate gradients. We conducted a study to determine whether the variation in the response of seed banks to temperature varied across the latitudinal range of Taxodium distichum swamps in North America. METHODS: The soil was collected in a long-term research network and heated experimentally to three current-day spring normal soil temperatures (average maximum daily spring normal soil temperatures during May in Illinois, Arkansas, and Louisiana, USA, respectively: 22 degrees , 25 degrees , and 29 degrees C). A "normal" is the mean temperature calculated over a 30-yr interval (1971-2000). Seed-bank density and biomass responses were examined in relation to latitude and difference in the soil temperature of the experiment and the spring normal. KEY RESULTS: Using first- and second-order regression analysis, we determined that the variation in total germination density was lowest mid-range and in experimental soil temperatures similar to the spring normal. For some dominant species, the variance in germination density was higher in the northern (Cephalanthus occidentalis) or the southern part of the network (Saururus cernuus and Polygonum pensylvanicum). Overall, the variance of total biomass (root, shoot, whole plant) was higher if the experimental soil temperature was warmer than the spring normal. CONCLUSIONS: Our results suggest that the regeneration of some populations of swamp species may have more flexibility to respond to climate warming than others. PMID- 22074776 TI - Who invented the dichotomous key? Richard Waller's watercolors of the herbs of Britain. AB - On 27 March 1689, Richard Waller, Fellow and Secretary of the Royal Society presented his "Tables of the English Herbs reduced to such an order, as to find the name of them by their external figures and shapes" to his assembled colleagues at a meeting of the Royal Society. These tables were developed for the novice by being color images, composed in pencil and watercolor, of selected plants and their distinguishing characteristics. The botanical watercolors for the tables are now a Turning-the-Pages document online on the website of the Royal Society. However, for the past 320 years, the scientific context for the creation of these outstanding botanical watercolors has remained obscure. These tables were developed by Waller as an image-based dichotomous key, pre-dating by almost 100 years the text-based dichotomous keys in the first edition of Flora Francaise (1778) by Jean Baptiste Lamarck, who is generally given priority for the development of the dichotomous key. How these large folio images were arranged to illustrate a dichotomous key is unknown, but an arrangement based on Waller's description is illustrated here as leaf-ordering for the separate hierarchical clusters (tables). Although only 24 species of watercolored dicot herbs out of a total of 65 in the set of watercolors (the others being monocots) are used in these tables, they are a "proof of concept", serving as models upon which a method is based, that of using a key composed of dichotomous choices for aiding identification. PMID- 22074777 TI - Nuclear and chloroplast SSR markers in Paeonia delavayi (Paeoniaceae) and cross species amplification in P. ludlowii. AB - PREMISE OF THE STUDY: Microsatellite primers were developed for Paeonia delavayi and P. ludlowii (Paeoniaceae) to study their population genetics and phytogeography. METHODS AND RESULTS: Nine polymorphic nuclear microsatellite loci were isolated from an enriched library of P. delavayi and primers were designed. The number of alleles per locus ranged from two to 16; the observed and expected heterozygosities ranged from 0.014 to 0.687 and 0.042 to 0.875, respectively. Six polymorphic chloroplast microsatellite loci were identified in P. delavayi and primers were provided. The number of alleles per locus ranged from two to six and the polymorphic information content ranged from 0.08 to 0.716. Both nuclear and chloroplast primers were successfully applicable to P. ludlowii. CONCLUSIONS: The markers developed here will facilitate analyses of genetic diversity, population genetic structure, phytogeographical patterns, and conservation for P. delavayi and P. ludlowii. PMID- 22074778 TI - Climate niches of milkweeds with plesiomorphic traits (Secamonoideae; Apocynaceae) and the milkweed sister group link ancient African climates and floral evolution. AB - PREMISE OF THE STUDY: Climate change that increases mortality of plants and pollinators can create mate-finding Allee effects and thus act as a strong selective force on floral morphology. Milkweeds (Secamonoideae and Asclepiadoideae; Apocynaceae) are typically small plants of seasonally dry habitats, with pollinia and high pollen-transfer efficiency. Their sister group (tribe Baisseeae and Dewevrella) is mostly comprised of giant lianas of African rainforests, with pollen in monads. Comparison of the two groups motivated a new hypothesis: milkweeds evolved in the context of African aridification and the shifting of rainforest to dry forest. Pollinia and high pollen-transfer efficiency may have been adaptations that alleviated mate-finding Allee effects generated by high mortality during droughts. We formally tested whether milkweeds have a drier climate niche by comparing milkweeds with plesiomorphic traits (Secamonoideae) and the milkweed sister group in continental Africa. METHODS: We georeferenced specimens of the milkweed sister group and Secamonoideae in continental Africa, extracted 19 climatic variables from the Worldclim model, conducted factor analysis to identify correlated suites of variables, and compared the frequency distributions of the two lineages relative to each factor. KEY RESULTS: The distributions of Secamonoideae and the milkweed sister group differed significantly relative to four factors, each correlated with a distinct suite of climate parameters: (1) air temperature (Secamonoideae: cooler), (2) total and (3) summer precipitation (Secamonoideae: drier), and (4) temperature seasonality and isothermality (Secamonoideae: more seasonal and less isothermal). CONCLUSIONS: Secamonoideae in continental Africa inhabit drier, cooler sites than do the milkweed sister group, consistent with a shift from rainforests to dry forests in a cooling climate. PMID- 22074779 TI - Three-dimensional imaging and photostimulation by remote-focusing and holographic light patterning. AB - Access to three-dimensional structures in the brain is fundamental to probe signal processing at multiple levels, from integration of synaptic inputs to network activity mapping. Here, we present an optical method for independent three-dimensional photoactivation and imaging by combination of digital holography with remote-focusing. We experimentally demonstrate compensation of spherical aberration for out-of-focus imaging in a range of at least 300 MUm, as well as scanless imaging along oblique planes. We apply this method to perform functional imaging along tilted dendrites of hippocampal pyramidal neurons in brain slices, after photostimulation by multiple spots glutamate uncaging. By bringing extended portions of tilted dendrites simultaneously in-focus, we monitor the spatial extent of dendritic calcium signals, showing a shift from a widespread to a spatially confined response upon blockage of voltage-gated Na(+) channels. PMID- 22074780 TI - Crystal structure of the GlnZ-DraG complex reveals a different form of PII-target interaction. AB - Nitrogen metabolism in bacteria and archaea is regulated by a ubiquitous class of proteins belonging to the P(II)family. P(II) proteins act as sensors of cellular nitrogen, carbon, and energy levels, and they control the activities of a wide range of target proteins by protein-protein interaction. The sensing mechanism relies on conformational changes induced by the binding of small molecules to P(II) and also by P(II) posttranslational modifications. In the diazotrophic bacterium Azospirillum brasilense, high levels of extracellular ammonium inactivate the nitrogenase regulatory enzyme DraG by relocalizing it from the cytoplasm to the cell membrane. Membrane localization of DraG occurs through the formation of a ternary complex in which the P(II) protein GlnZ interacts simultaneously with DraG and the ammonia channel AmtB. Here we describe the crystal structure of the GlnZ-DraG complex at 2.1 A resolution, and confirm the physiological relevance of the structural data by site-directed mutagenesis. In contrast to other known P(II) complexes, the majority of contacts with the target protein do not involve the T-loop region of P(II). Hence this structure identifies a different mode of P(II) interaction with a target protein and demonstrates the potential for P(II) proteins to interact simultaneously with two different targets. A structural model of the AmtB-GlnZ-DraG ternary complex is presented. The results explain how the intracellular levels of ATP, ADP, and 2 oxoglutarate regulate the interaction between these three proteins and how DraG discriminates GlnZ from its close paralogue GlnB. PMID- 22074781 TI - Detection of beta cell death in diabetes using differentially methylated circulating DNA. AB - In diabetes mellitus, beta cell destruction is largely silent and can be detected only after significant loss of insulin secretion capacity. We have developed a method for detecting beta cell death in vivo by amplifying and measuring the proportion of insulin 1 DNA from beta cells in the serum. By using primers that are specific for DNA methylation patterns in beta cells, we have detected circulating copies of beta cell-derived demethylated DNA in serum of mice by quantitative PCR. Accordingly, we have identified a relative increase of beta cell-derived DNA after induction of diabetes with streptozotocin and during development of diabetes in nonobese diabetic mice. We have extended the use of this assay to measure beta cell-derived insulin DNA in human tissues and serum. We found increased levels of demethylated insulin DNA in subjects with new-onset type 1 diabetes compared with age-matched control subjects. Our method provides a noninvasive approach for detecting beta cell death in vivo that may be used to track the progression of diabetes and guide its treatment. PMID- 22074782 TI - Direct regulation of nucleosome density by the conserved AAA-ATPase Yta7. AB - Yta7 is a highly conserved bromodomain-containing protein with AAA-ATPase homology originally implicated in heterochromatin boundary function in Saccharomyces cerevisiae. Although increased activity of the human ortholog has been implicated in malignant breast tumors, Yta7's precise mode of action is unknown. Transcriptional analysis in yeast cells revealed a role for Yta7 and its ATPase function in gene induction, including galactose- and sporulation-induced transcription. This requirement was direct and activating, because Yta7 associated with the GAL gene cluster only upon transcriptional induction. Suggestive of a role in transcriptional elongation, Yta7 localized to the ORFs of highly transcribed genes. Intriguingly, the yta7Delta mutant's transcriptional defects were partially suppressed by decreased dosage of histones H3 and H4. Consistent with this suppression, cells lacking Yta7 exhibited both increased levels of chromatin-incorporated histone H3 and decreased nucleosome spacing. Importantly, this modulation of H3 levels occurred independently of changes in H3 transcript level. Because Yta7 binds histone H3 in vitro, these results suggested a direct role for Yta7 in H3 eviction or degradation. Further, local loss of Yta7 activity at a long inducible gene resulted in accumulation of H3 at the 3' end upon transcriptional activation, implying Yta7 may regulate H3 cotranscriptionally. PMID- 22074784 TI - Emerging role of innate immunity in organ transplantation part II: potential of damage-associated molecular patterns to generate immunostimulatory dendritic cells. AB - Part 2 of the review focuses on the potential of oxidative injury-induced damage associated molecular patterns (DAMPs) to generate immunostimulatory dendritic cells (DCs) translating innate to adaptive immunity. Four different classes of DAMPs are defined, and their potential role in mediating pathways contributing to maturation of immunostimulatory DCs is explored and discussed. Accordingly, injury-induced molecules are divided into (1) class I DAMPs that, when recognized by pattern recognition receptors of DCs, trigger their activation; (2) class II DAMPs that are recognized by special activating receptors on innate lymphocytes that, after activation, contribute to maturation of DCs; (3) class III DAMPs that are recognized by pattern recognition receptors involved in the activation of inflammasomes, that is, molecular platforms that trigger the activation of proinflammatory cytokines promoting maturation of DCs; and (4) class IV DAMPs in terms of neoantigens that are recognized by preexisting natural immunoglobulin M antibodies, which-via complement activation-are able to aggravate the oxidative tissue injury and, thereby, may indirectly promote maturation of DCs. These new insights into mechanisms of oxidative injury-mediated generation of immunostimulatory DCs are finally discussed by addressing possible novel therapeutic strategies with the aim to prevent the capacity of oxidative injury to induce DAMPs in the donor organ. The ultimate goal of those strategies will be to induce transplant tolerance by avoiding oxidative injury in the donor and the recipient and thereby inhibiting activation of immunostimulatory DCs but promoting activation of tolerogenic DCs. PMID- 22074783 TI - Role of T cell-nuclear factor kappaB in transplantation. AB - Nuclear factor (NF) kappaB is a pleiotropic transcription factor that is ubiquitously expressed. After transplantation of solid organs, NF-kappaB in the graft is activated within a few hours as a consequence of ischemia/reperfusion and then again after a few days in intragraft infiltrating cells during the process of acute allograft rejection. In the present article, we review the components of the NF-kappaB pathway, their mechanisms of activation, and their role in T cell and antigen-presenting cell activation and differentiation and in solid organ allograft rejection. Targeted inhibition of NF-kappaB in selected cell types may promote graft survival with fewer adverse effects compared with global immunosuppressive therapies. PMID- 22074785 TI - Protective effects of hypothermic ex vivo perfusion on ischemia/reperfusion injury and transplant outcomes. AB - Hypothermic machine preservation (HMP) has been used in renal transplantation since the late 1960s with recent robust prospective, multicenter data showing lower rates of delayed graft function and improved graft survival. Although now clearly beneficial for renal transplantation, extrarenal machine perfusion has remained predominantly in preclinical investigations. Pancreatic HMP has drawn little clinical interest because HMP has been suggested to cause graft edema and congestion, which is associated with early venous thrombosis and graft failure. Early investigation showed no benefit of HMP in whole-organ pancreas transplant. One report did show that HMP increases islet cell yield after isolation. Preclinical work in liver HMP has been promising. Short- and long-term HMP has been shown to improve graft viability and reduce preservation injury, even in animal models of steatotic and donation after cardiac death. The first clinical study of liver HMP using a centrifugal dual perfusion technique showed excellent results with lower hepatocellular injury markers and no adverse perfusion-related outcomes. In addition, a dramatic attenuation of proinflammatory cytokine expression was observed. Further studies of liver HMP are planned with focus on developing a reproducible and standard protocol that will allow the widespread availability of this technology. Future research and clinical trials of novel organ preservation techniques, solutions, and interventions are likely to bring about developments that will allow further reduction of preservation-related ischemia/reperfusion injury and improved outcomes and allow safer utilization of the precious and limited resource of donor organs. PMID- 22074787 TI - Phenomics--technologies to relieve the phenotyping bottleneck. AB - Global agriculture is facing major challenges to ensure global food security, such as the need to breed high-yielding crops adapted to future climates and the identification of dedicated feedstock crops for biofuel production (biofuel feedstocks). Plant phenomics offers a suite of new technologies to accelerate progress in understanding gene function and environmental responses. This will enable breeders to develop new agricultural germplasm to support future agricultural production. In this review we present plant physiology in an 'omics' perspective, review some of the new high-throughput and high-resolution phenotyping tools and discuss their application to plant biology, functional genomics and crop breeding. PMID- 22074788 TI - Working alliance, interpersonal trust and perceived coercion in mental health review hearings. AB - BACKGROUND: There is some evidence that when mental health commitment hearings are held in accordance with therapeutic jurisprudence principles they are perceived as less coercive, and more just in their procedures leading to improved treatment adherence and fewer hospital readmissions. This suggests an effect of the hearing on therapeutic relationships. We compared working alliance and interpersonal trust in clinicians and forensic patients, whose continued detentions were reviewed by two different legal review bodies according to their legal category. METHODS: The hearings were rated as positive or negative by patients and treating psychiatrists using the MacArthur scales for perceived coercion, perceived procedural justice (legal and medical) and for the impact of the hearing. We rated Global assessment of Function (GAF), Positive and Negative Symptom Scale (PANSS), Working Alliance Inventory (WAI) and Interpersonal Trust in Physician (ITP) scales six months before the hearing and repeated the WAI and ITP two weeks before and two weeks after the hearing, for 75 of 83 patients in a forensic medium and high secure hospital. RESULTS: Psychiatrists agreed with patients regarding the rating of hearings. Patients rated civil hearings (MHTs) more negatively than hearings under insanity legislation (MHRBs). Those reviewed by MHTs had lower scores for WAI and ITP. However, post-hearing WAI and ITP scores were not different from baseline and pre-hearing scores. Using the receiver operating characteristic, baseline WAI and ITP scores predicted how patients would rate the hearings, as did baseline GAF and PANSS scores. CONCLUSIONS: There was no evidence that positively perceived hearings improved WAI or ITP, but some evidence showed that negatively perceived hearings worsened them. Concentrating on functional recovery and symptom remission remains the best strategy for improved therapeutic relationships. PMID- 22074786 TI - T-cell activation and transplantation tolerance. AB - Transplantation of allogeneic or "nonself" tissues stimulates a robust immune response leading to graft rejection, and therefore, most recipients of allogeneic organ transplants require the lifelong use of immune suppressive agents. Excellent outcomes notwithstanding, contemporary immunosuppressive medications are toxic, are often not taken by patients, and pose long-term risks of infection and malignancy. The ultimate goal in transplantation is to develop new treatments that will supplant the need for general immunosuppression. Here, we will describe the development and application of costimulation blockade to induce transplantation tolerance and discuss how the diverse array of signals that act on T cells will determine the balance between graft survival and rejection. PMID- 22074789 TI - Predictors of vitamin D status in predialysis chronic kidney disease patients: a cross-sectional analysis in a high ultraviolet climate. AB - OBJECTIVE: To determine vitamin D status in a subtropical climate among an unselected, referred predialysis chronic kidney disease (CKD) population; assess risks and correlates; and review whether higher 25-hydroxyvitamin D (25-OHD) concentration can mitigate the decrement in circulating 1,25-dihydroxyvitamin D (1,25-OHD) normally encountered with advancing CKD. DESIGN: Prospective cross sectional cohort study. SETTING: Renal unit in Brisbane, Australia (27 degrees 28' S). SUBJECTS: Five hundred ninety-three consecutive CKD patients (stage 1 to 5). MAIN OUTCOME MEASURE: 25-OHD insufficiency (concentrations: 15 to 30 ng/mL) and deficiency (<15 ng/mL), bone-mineral parameters, including 1,25-OHD, calcium, and phosphate. RESULTS: Despite potentially higher environmental ultraviolet (UV) exposure, only 48% of patients with CKD were 25-OHD sufficient. Traditional risks for hypovitaminosis D were maintained, and sufficiency was independently predicted by testing in the summer/autumn period (odds ratio [OR]: 2.77, 95% confidence interval [CI]: 1.88 to 4.08, P < .001), male gender (OR: 2.18, 95%CI: 1.46 to 3.24, P < .001), Caucasian race (OR: 2.28, 95%CI: 1.37 to 3.78, P = .001), hypoalbuminemia (OR: 0.47, 95%CI: 0.25 to 0.85, P = .01), macroalbuminuria (OR: 0.60, 95%CI: 0.39 to 0.92, P = .02), and normal body mass index (OR: 1.94, 95%CI: 1.22 to 3.07, P = .005). Vitamin D sufficiency was also associated with higher corrected calcium (0.4 mg/dL increments; OR: 1.29, 95%CI: 1.08 to 1.55, P = .005). Although circulating 25-OHD concentrations were relatively maintained across the range of renal function observed, 1,25-OHD concentrations decreased with advancing CKD. CONCLUSION: 25-OHD insufficiency is mitigated but still highly prevalent in patients with CKD in a high ambient UV environment. Despite the maintenance of relatively higher 25-OHD concentrations with advancing CKD, substrate availability does not appear to be a major determinant of circulating 1,25-OHD. PMID- 22074790 TI - Demonstration of cell membrane permeabilization to medium-sized molecules caused by a single 10 ns electric pulse. AB - In our study, we used bleomycin to evaluate the permeabilization caused by nanosecond duration electric pulses (nanopulses). Bleomycin is a non permeant molecule which can be used both as a sensitive and quantitative marker to evaluate cell electropermeabilization. Indeed, the penetration of as few as 500 molecules is sufficient to entail a major biological effect: cell death. We show that one single nanopulse with a duration of 10 ns and a field strength of 40 kV/cm is sufficient to allow the uptake of at least 500 molecules of bleomycin in 20% of the cells when the external bleomycin concentration is 3 MUM. When the external bleomycin concentration is reduced by a 100 fold, the same levels of cytotoxicity require an increase of about 25 times in the number of pulses. These results are in favor of the fact that each nanopulse creates new pores or defects on the cell membrane even if most of these pores can reseal between two consecutive pulses. Results also suggest that the cell permeability observed with classical markers when a large number of pulses are delivered results from the large number of nanopores or defects of the cell membrane created by the train of nanopulses. PMID- 22074791 TI - Viral respiratory infections during the 2009 influenza A(H1N1) outbreak in the West Midlands Region, UK. AB - In spring 2009 a new strain of influenza A(H1N1) emerged and caused a worldwide pandemic. This study utilized a large collection of respiratory specimens from suspected cases of influenza A(H1N1) in the UK West Midlands during the pandemic in order to investigate which other respiratory viruses were circulating and whether they played any role in the increased hospitalization rates seen during that period. Study specimens were selected from community and hospitalized patients positive and negative for influenza A(H1N1) and tested by PCR for other respiratory viruses. A number of infections diagnosed as influenza during the summer influenza outbreak were found to be due to other virus infections (most commonly rhinovirus). No statistically significant difference was found between the rates of respiratory virus co-infection with H1N1 in patients from community or hospital locations suggesting underlying factors were likely to be more significant than viral co-infections in determining severity of influenza A(H1N1) disease. PMID- 22074792 TI - Screening for natural chemoprevention agents that modify human Keap1. AB - Upregulation of cytoprotective enzymes by therapeutic agents to prevent damage by reactive oxygen species and xenobiotic electrophiles is a strategy for cancer chemoprevention. The Kelch-like ECH-associated protein 1 (Keap1) and its binding partner, transcription factor NF-E2-related factor-2 (NRF2), are chemoprevention targets because of their role in regulating the antioxidant response element (ARE) in response to oxidative stress and exposure to electrophiles. Modification of the sensor protein Keap1 by electrophiles such as the isothiocyanate sulforaphane can direct Nrf2 accumulation in the nucleus and subsequent ARE activation. Since our previous matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS)-based screening method to discover natural products that modify Keap1 does not detect covalent modification of Keap1 by some highly reversible agents such as sulforaphane, a more sensitive screening assay was developed. In this new assay, electrophiles that have reversibly modified Keap1 can be released, trapped, and detected as beta-mercaptoethanol adducts by mass spectrometry. Isoliquiritigenin and sulforaphane, known ARE activators that target Keap1, were used to validate the assay. To determine the ability of the assay to identify electrophiles in complex matrixes that modify Keap1, sulforaphane was spiked into a cocoa extract, and LC-MS/MS using high resolution mass spectrometry with accurate mass measurement was used to identify beta mercaptoethanol adducts of sulforaphane that had been released from Keap1. This screening assay permits identification of potential chemoprevention agents in complex natural product mixtures that reversibly modify Keap1 but cannot be detected using MALDI-TOF MS. PMID- 22074793 TI - Piezoelectric detection of bilirubin based on bilirubin-imprinted titania film electrode. AB - A novel quartz crystal microbalance (QCM) sensor with a high selectivity and sensitivity has been developed for bilirubin determination, based on the modification of bilirubin-imprinted titania film onto a quartz crystal by molecular imprinting and surface sol-gel techniques. The performance of the developed bilirubin biosensor was evaluated and the results indicated that a sensitive bilirubin biosensor could be fabricated. The obtained bilirubin biosensor presents high-selectivity monitoring of bilirubin, better reproducibility, shorter response time (30 min), wider linear range (0.1-50 MUM), and lower detection limit (0.05 MUM). The analytical application of the bilirubin biosensor confirms the feasibility of bilirubin determination in serum sample. PMID- 22074794 TI - Label-free fluorescence method for screening G-quadruplex ligands. AB - G-quadruplex ligands can interfere with the telomere structure, telomere elongation/replication, and proliferation of cancer cells. A key element in the development of potent G-quadruplex ligands is the screening of large chemical libraries of potential candidates. Here, we describe a simple fluorescence method for screening of G-quadruplex ligands. The method is based on the ability of G quadruplex ligands to displace hemin from G-quadruplex-based DNAzyme, resulting in a decrease of its catalytic activity on the fluorescence-developing reaction between p-hydroxyphenylacetic acid and H(2)O(2). The method eliminates the requirement for expensive and time-consuming preparation of labeled DNA. Our method provides a simple, cheap, and sensitive approach to screen G-quadruplex ligands (potential antitumor drugs). PMID- 22074795 TI - Identification of reference microRNAs and suitability of archived hemopoietic samples for robust microRNA expression profiling. AB - In many cancers, including neuroblastoma, microRNA (miRNA) expression profiling of peripheral blood (PB) and bone marrow (BM) may increase understanding of the metastatic process and lead to the identification of clinically informative biomarkers. The quality of miRNAs in PB and BM samples archived in PAXgeneTM blood RNA tubes from large-scale clinical studies and the identity of reference miRNAs for standard reporting of data are to date unknown. In this study, we evaluated the reliability of expression profiling of 377 miRNAs using quantitative polymerase chain reaction (qPCR) in PB and BM samples (n=90) stored at -80 degrees C for up to 5 years in PAXgeneTM blood RNA tubes. There was no correlation with storage time and variation of expression for any single miRNA (r < 0.50). The profile of miRNAs isolated as small RNAs or co-isolated with small/large RNAs was highly correlated (r=0.96). The mean expression of all miRNAs and the geNorm program identified miR-26a, miR-28-5p, and miR-24 as the most stable reference miRNAs. This study describes detailed methodologies for reliable miRNA isolation and profiling of PB and BM, including reference miRNAs for qPCR normalization, and demonstrates the suitability of clinical samples archived at -80 degrees C into PAXgeneTM blood RNA tubes for miRNA expression studies. PMID- 22074796 TI - Involvement of C-type inactivation gating in the actions of voltage-gated K+ channel inhibitors. AB - Voltage-gated K(+) (Kv) channels serve multiple functions. Besides the most well known function of controlling membrane excitability, they may also play roles in cell death and differentiation. Pharmacological activators and inhibitors of Kv channels therefore offer potential therapeutic treatments for a variety of diseases. Inhibition of Kv channels by classical blockers such as tetraethylammonium and 4-aminopyridine, and toxin peptides such as scorpion toxins, are believed to result from a direct intervention or occlusion of the K(+) permeation pathway. During prolonged depolarization, most Kv channels undergo a process called slow or C-type inactivation, by which the selectivity filter destabilizes and thus limits K(+) flux. Increasing amount of evidence shows that there are certain compounds which inhibit Kv currents not by directly obstructing the K(+) conduction pathway, but by accelerating or intensifying selectivity filter destabilization once the channels open. This mode of block represents an alternative mechanism of Kv channel inhibition. Indeed, some of the classical Kv channel blockers are to some extent, or in certain circumstances, involved in hastening slow inactivation. This review begins with a brief description of structure-functions of Kv channels, and then discusses the multiple mechanisms of Kv channel inhibition by classical blockers and how certain compounds inhibit Kv channels by accelerating C-type inactivation. The pharmacological and therapeutic potentials of these C-type inactivation-dependent Kv channel inhibitors are discussed. PMID- 22074797 TI - Tea flavan-3-ols as modulating factors in endoplasmic reticulum function. AB - Regular green tea consumption has been shown to reduce the risk of cancer and diabetes mellitus. These effects are attributed to tea flavan-3-ols, especially to epigallocatechin gallate; however, the molecular targets and mechanisms of action are still subject of extensive research. The special roles of the endoplasmic reticulum (ER) in biotransformation, protein synthesis, calcium homeostasis, and glucose production make this organelle a potential target of the antitumor and antidiabetic effects of tea flavan-3-ols. The purpose of this review is to present evidence for the biologic actions of tea flavan-3-ols on specific ER targets associated with normal function and disease. Reactivation of chemical carcinogens can be reduced by tea flavan-3-ols through inhibition of glucuronide transport across the ER membrane. Catechins modulate Ca(2+) release from the ER lumen and interfere with glycoprotein maturation, which can lead to decreased viability and increased drug sensitivity of tumor cells. Epigallocatechin gallate inhibits glucose transport across the ER membrane, which can underlie the reduction of hepatic glucose production by tea flavan-3-ols. These mechanisms likely contribute to the chemopreventive and glucose-lowering effects of tea catechins. Investigating the effects of flavan-3-ols on ER functions is a promising field of medical and biochemical research to understand disease and improve health. PMID- 22074798 TI - Socioeconomic status and chronic child malnutrition: Wealth and maternal education matter more in the Peruvian Andes than nationally. AB - This study investigated the association of parents' socioeconomic status (SES) with child stunting in the Peruvian Andes and in Peru nationally. It was hypothesized that the relationship of SES to child stunting would be weaker in the Andean compared with the national sample. This is consistent with earlier research indicating that the relationship of SES to health may be weak in poor regions. The data were from the Demographic and Health Survey 2004 to 2006. Two samples of children 3 to 60 months old were compared: a national sample (n = 1426) and an Andean sample (n = 543). Malnutrition was measured using the indicator "stunting," which is small stature for age. Socioeconomic status was measured using parental education, occupation, and household wealth index (WI). In both samples, SES was significantly related to stunting. The odds of stunting in the poorest WI quintile were significantly higher than in the richest quintile. The same pattern was observed in children of mothers having incomplete primary education compared with children of mothers having complete secondary or higher education. The odds of stunting were significantly lower in children of mothers working at home compared with mothers in professional occupations. The associations of WI and maternal education with stunting were significantly stronger in the Andean compared with the national sample; the study did not find support for the hypothesis. Even in very poor regions such as the Andes, SES may be associated with child health, suggesting the importance of public health measures to overcome the health disadvantages experienced by children living in low SES households. PMID- 22074799 TI - Urbanization of black South African women may increase risk of low bone mass due to low vitamin D status, low calcium intake, and high bone turnover. AB - Globally, rural to urban migration is accompanied by changes in dietary patterns and lifestyle that have serious health implications, including development of low bone mass. We hypothesized that serum 25 (OH) vitamin D3 (25[OH]D3) levels will be lower, bone turnover higher, and nutrition inadequate in urban postmenopausal black women, increasing risk for low bone mass. We aimed to assess the prevalence of risk factors for low bone mass in 1261 black women from rural and urban areas in the North West Province of South Africa (Prospective Urban and Rural Epidemiology-South Africa project). Fasting blood samples were taken; and participants were interviewed to complete questionnaires on self-reported diseases, fractures, and dietary intakes. Bone health markers were assessed in a subgroup of 658 women older than 45 years. Specific lifestyle risk factors identified were inactivity, smoking, injectable progestin contraception use, and high alcohol consumption. Dietary risk factors identified were low calcium and high animal protein, phosphorous, and sodium intakes. The 25(OH)D3 and C-terminal telopeptide (CTX) levels were significantly higher in the rural vs the urban women older than 50 years. Parathyroid hormone (PTH) levels increased with age in both groups. The 25(OH)D levels were inversely correlated with CTX and PTH in rural women. In urban women, PTH and CTX were correlated while dietary calcium was inversely correlated with CTX and PTH with 25(OH)D3. The combination of low dietary calcium (<230 mg/d), marginally insufficient 25(OH)D3 status, and raised PTH may result in increased bone resorption. Further research is required to assess bone health and fracture risk in black African women. PMID- 22074800 TI - Nutrients from dairy foods are difficult to replace in diets of Americans: food pattern modeling and an analyses of the National Health and Nutrition Examination Survey 2003-2006. AB - Because dairy products provide shortfall nutrients (eg, calcium, potassium, and vitamin D) and other important nutrients, this study hypothesized that it would be difficult for Americans to meet nutritional requirements for these nutrients in the absence of dairy product consumption or when recommended nondairy calcium sources are consumed. To test this hypothesis, MyPyramid dietary pattern modeling exercises and an analyses of data from the National Health and Nutrition Examination Survey 2003-2006 were conducted in those aged at least 2 years (n = 16 822). Impact of adding or removing 1 serving of dairy, removing all dairy, and replacing dairy with nondairy calcium sources was evaluated. Dietary pattern modeling indicated that at least 3 servings of dairy foods are needed to help individuals meet recommendations for nutrients, such as calcium and magnesium, and 4 servings may be needed to help some groups meet potassium recommendations. A calcium-equivalent serving of dairy requires 1.1 servings of fortified soy beverage, 0.6 serving of fortified orange juice, 1.2 servings of bony fish, or 2.2 servings of leafy greens. The replacement of dairy with calcium-equivalent foods alters the overall nutritional profile of the diet and affects nutrients including protein, potassium, magnesium, phosphorus, riboflavin, vitamins A, D and B(12). Similar modeling exercises using consumption data from the National Health and Nutrition Examination Survey also demonstrated that nondairy calcium replacement foods are not a nutritionally equivalent substitute for dairy products. In conclusion, although it is possible to meet calcium intake recommendations without consuming dairy foods, calcium replacement foods are not a nutritionally equivalent substitute for dairy foods and consumption of a calcium-equivalent amount of some nondairy foods is unrealistic. PMID- 22074801 TI - Soy milk and dairy consumption is independently associated with ultrasound attenuation of the heel bone among postmenopausal women: the Adventist Health Study-2. AB - Soy milk has become a popular substitute for dairy milk with important health claims. We hypothesized that soy milk, based on its nutrient composition, is comparable to dairy products and, therefore, beneficial for bone health. To test this hypothesis, we examined the benefit of soy milk and dairy products intake on bone health using broadband ultrasound attenuation of the calcaneus. Postmenopausal white women (n = 337) who had completed a lifestyle and dietary questionnaire at enrollment into the Adventist Health Study-2 had their calcaneal broadband ultrasound attenuation measured 2 years later. The association between osteoporosis (defined as a T-score <-1.8) and some dietary factors (soy milk, dairy) and selected lifestyle factors was assessed using logistic regression. In a multivariable model adjusted for demographics, hormone use, and other dietary factors, osteoporosis was positively associated with age (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.06-1.12) and inversely associated with body mass index (OR = 0.91; 95% CI, 0.86-0.97) and current estrogen use (OR = 0.27; 95% CI, 0.13-0.56). Compared with women who did not drink soy milk, women drinking soy milk once a day or more had 56% lower odds of osteoporosis (OR = 0.44; 95% CI, 0.20-0.98; P(trend) = .04). Women whose dairy intake was once a day or more had a 62% reduction in the likelihood of having osteoporosis (OR = 0.38; 95% CI, 0.17 0.86; P(trend) = .02) compared with women whose dairy intake was less than twice a week. Among individual dairy products, only cheese showed an independent and significant protection (OR = 0.28; 95% CI, 0.12-0.66; P(trend) = .004) for women eating cheese more than once per week vs those who ate cheese less than once a week. We concluded that osteoporosis is inversely associated with soy milk intake to a similar degree as dairy intake after accounting for age, body mass index, and estrogen use. PMID- 22074802 TI - Fresh and fresh lean pork are substantial sources of key nutrients when these products are consumed by adults in the United States. AB - Many fresh pork products, in particular, fresh lean pork products, are nutrient dense sources of protein and several other nutrients. The purpose of this study was to estimate nutritional contributions of fresh and fresh lean pork to adults' diets in the United States. Mean total nutrient intakes by fresh and fresh lean pork consumers on a day of recall were compared with intakes by nonconsumers to test the hypothesis that overall nutrient intakes by consumers were comparable with or better as compared with intakes by nonconsumers. Intakes were assessed using the National Health and Nutrition Examination Survey 2003 to 2006. Based on 1 day of dietary intake, 10% of adults consumed fresh pork, and 4% consumed fresh lean pork. Among consumers, fresh and fresh lean pork contributed 16% and 9%, respectively, of total fat and accounted for 23% to 31% of total protein, cholesterol, selenium, and thiamin intake. Fresh and fresh lean pork also accounted for 11% to 19% of total saturated fat, phosphorus, potassium, riboflavin, niacin, vitamin B(6), and vitamin B(12) in the diets of consumers and contributed 21% and 16%, respectively, of total zinc. Diets including fresh or fresh lean pork provided higher energy-adjusted amounts of protein, selenium, thiamin, and vitamin B(6) as compared with diets of adults not consuming fresh pork (P < .05) and provided comparable amounts of fat and saturated fat. Consumption of lean cuts of fresh pork is consistent with dietary guidance, and selection of fresh lean pork products by current nonconsumers could increase dietary variety without adversely affecting nutrient intake. PMID- 22074803 TI - Astaxanthin inhibits thrombosis in cerebral vessels of stroke-prone spontaneously hypertensive rats. AB - It is known that vitamin E and some carotenoids have antioxidant activities that alleviate endothelial dysfunction and play a protective role against cardiovascular disease. The current study was designed to examine the hypothesis that astaxanthin, a red pigment carotenoid found in salmonid and crustacean aquaculture, protects stroke-prone spontaneously hypertensive rats (SHRSP) from vascular oxidative damage, hypertension, and cerebral thrombosis. Male 6-week-old SHRSP were classified into 4 groups: a control group, 2 astaxanthin groups, and a vitamin E group. The treated animals were given either astaxanthin or vitamin E for 3 weeks. Body weights in each group were not significantly different from control group during the treatment period, but the usual increase in systolic blood pressure in SHRSP observed with age was significantly suppressed by treatment. Thrombogenesis, assessed using a helium-neon (He-Ne) laser technique in pial blood vessels, together with antioxidant activity, assessed by measuring urinary 8-OHdG levels, were significantly moderated. Urinary nitric oxide (NO) metabolites were increased after treatment. These results supported our hypothesis and strongly suggested that the antithrombotic and antihypertensive effects of astaxanthin or vitamin E may be related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species. PMID- 22074804 TI - Dietary methyl donor deficiency during pregnancy in rats shapes learning and anxiety in offspring. AB - Two important lines of research have enhanced our understanding of the molecular role of nutrition in influencing behavior. First, exposure to an adverse environment during early life can influence the long-term behavior of the offspring. Second, regulation of the nervous system development and functioning appears to involve epigenetic mechanisms that require a continuous supply of methyl group donors in food. We hypothesized that a maternal diet during pregnancy deficient in methyl donors (MDD) may lead to altered behavior in offspring through permanent changes in hippocampal DNA methylation. We used a rat model of prenatal dietary MDD to test this hypothesis in female offspring as they aged. Prenatal MDD reduced birth weight, litter size, and newborn viability. Aged female offspring of MDD mothers showed increased anxiety and increased learning ability in comparison with control diet group offspring. To explore the role of MDD on epigenetic mechanisms in the brain of adult offspring, we studied expression and methylation of 4 selected genes coding for glucocorticoid receptor, hydroxysteroid dehydrogenase 11 type 2, neuronatin, and reelin proteins in the hippocampus. No major group differences in methylation or expression of the studied genes were detected, except for a significant down-regulation of the reelin gene in the MDD female offspring. The prenatal MDD diet caused intrauterine growth restriction, associated with long-term effects on the behavior of the offspring. However, the observed behavioral differences between the MDD and control diet offspring cannot be explained by epigenetic regulation of the specific genes investigated in this study. PMID- 22074805 TI - L-amino acid decarboxylase- and tyrosine hydroxylase-immunoreactive cells in the extended olfactory amygdala and elsewhere in the adult prairie vole brain. AB - Neurons synthesizing dopamine (DA) are widely distributed in the brain and implicated in a tremendous number of physiological and behavioral functions, including socioreproductive behaviors in rodents. We have recently been investigating the possible involvement of sex- and species-specific TH immunoreactive (TH-ir) cells in the male prairie vole (Microtus ochrogaster) principal bed nucleus of the stria terminalis (pBST) and posterodorsal medial amygdala (MeApd) in the chemosensory control of their monogamous pairbonding and parenting behaviors. These TH-ir cells are not immunoreactive for dopamine-beta hydroxylase (DBH), suggesting they are not noradrenergic but possibly DAergic. A DAergic phenotype would require them to contain aromatic L-amino acid decarboxylase (AADC) and here we examined the existence of cells immunoreactive for both TH and AADC in the pBST and MeApd of adult virgin male and female prairie voles. We also investigated the presence of TH/AADC cells in the anteroventral periventricular nucleus (AVPV), medial preoptic area (MPO), arcuate nucleus (ARH), zona incerta (ZI), substantia nigra (SN) and ventral tegmental area (VTA). Among our findings were: (1) the pBST and MeApd each contained completely non-overlapping distributions of TH-ir and AADC-ir cells, (2) the AVPV contained surprisingly few AADC-ir cells and almost no TH-ir cells contained AADC ir, (3) approximately 60% of the TH-ir cells in the MPO, ARH, and ZI also contained AADC-ir, (4) unexpectedly, only about half of TH-ir cells in the SN and VTA contained AADC-ir, and (5) notable populations of AADC-ir cells were found outside traditional monoamine-synthesizing regions, including some sites that do not contain AADC-ir cells in adult laboratory rats or cats (medial septum and cerebral cortex). In the absence of the chemical requirements to produce DA, monoenzymatic TH-ir cells in the virgin adult prairie vole pBST, MeApd, and elsewhere in their brain may instead produce L-DOPA as an end product and use it as a neurotransmitter or neuromodulator, similar to what has been observed for monoenzymatic TH-synthesizing cells in the laboratory rat brain. PMID- 22074806 TI - Age-associated loss of selectivity in human olfactory sensory neurons. AB - We report a cross-sectional study of olfactory impairment with age based on both odorant-stimulated responses of human olfactory sensory neurons (OSNs) and tests of olfactory threshold sensitivity. A total of 621 OSNs from 440 subjects in 2 age groups of younger (<= 45 years) and older (>= 60 years) subjects were investigated using fluorescence intensity ratio fura-2 imaging. OSNs were tested for responses to 2 odorant mixtures, as well as to subsets of and individual odors in those mixtures. Whereas cells from younger donors were highly selective in the odorants to which they responded, cells from older donors were more likely to respond to multiple odor stimuli, despite a loss in these subjects' absolute olfactory sensitivity, suggesting a loss of specificity. This degradation in peripheral cellular specificity may impact odor discrimination and olfactory adaptation in the elderly. It is also possible that chronic adaptation as a result of reduced specificity contributes to observed declines in absolute sensitivity. PMID- 22074807 TI - No association of ALOX5AP polymorphisms with risk of MRI-defined brain infarcts. AB - The arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene has been associated with stroke. The majority of the reported ALOX5AP associations have considered non-radiologically confirmed infarcts as the stroke phenotype. We assessed the association of genetic variants in ALOX5AP with stroke defined by the presence of infarcts on brain magnetic resonance imaging (MRI). We studied 202 persons with MRI-defined brain infarcts and 487 healthy individuals of Caribbean Hispanic ancestry. Another sample of European ancestry comprised 1823 persons with MRI-defined brain infarct and 7578 control subjects. Subjects were genotyped for the 4 single nucleotide polymorphisms (SNPs) that define ALOX5AP HapA haplotype. No association was found between SNPs and MRI-defined brain infarcts. Our data do not support the hypothesis that variants in ALOX5AP are associated with risk of MRI-defined brain infarcts. PMID- 22074808 TI - Taxol alleviates 2-methoxyestradiol-induced endothelial permeability. AB - We have previously shown that the anti-cancer agent 2-methoxyestradiol (2ME) induces hyperpermeability across endothelial monolayers. Here, we show that both microtubule disruptor, 2ME, and microtubule stabilizer, paclitaxel (taxol), increase vascular lung permeability in vitro and in vivo. Simultaneous application of 2ME and taxol alleviates 2ME-induced endothelial barrier dysfunction, which is evident by the decreased Evans Blue Dye accumulation in lung tissue and increased transendothelial resistance across monolayers. 2ME significantly increases the level of p38 and MLC phosphorylation in both endothelial monolayers and murine lungs; this increase is suppressed in the presence of taxol. Taxol treatment leads to an immediate and sustained increase in tubulin acetylation in human pulmonary artery endothelial cells (HPAEC). Surprisingly, 2ME treatment also increases tubulin acetylation; however, the onset of this process is delayed and coincides with the stage of a partial barrier restoration in HPAEC monolayer. Inhibition of histone deacetylase 6 (HDAC6) with tubacin increases tubulin acetylation level, suppresses 2ME-induced HSP27 and MLC phosphorylation, and decreases 2ME-induced barrier dysfunction, suggesting barrier-protective and/or barrier-restorative role for tubulin acetylation in vascular endothelium. PMID- 22074809 TI - AMP-activated protein kinase and the control of smooth muscle cell hyperproliferation in vascular disease. AB - Smooth muscle cell (SMC) accumulation within the arterial intima contributes to the formation of atherosclerotic lesions. Emerging data indicate that the adenosine monophosphate-activated protein kinase (AMPK) is a potent inhibitor of SMC proliferation. The anti-proliferative action of AMPK is mediated through multiple mechanisms, including the regulation of cyclin dependent kinase inhibitors expression p21(Cip1) and p27(kip1) and the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). A favorable effect of AMPK activation on intima hyperplasia has been demonstrated in in vivo experimental models by using the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), or by studying the AMPKalpha(-/-) mice. Starting from these evidences, a number of atheroprotective drugs with antiproliferative properties have been shown to induce AMPK phosphorylation. Among them, the Ca(2+) channel blocker nifedipine was demonstrated to act through AMPK, independent of its calcium channel blocking activity. In the present review I summarize current knowledge on the basic biological function of AMPK in relationship to vascular SMC proliferation; the evidence for the role of AMPK in in vivo intima hyperplasia; and the drugs for which a pharmacological activity on AMPK has been shown. PMID- 22074810 TI - Electrochemical sensor based on molecularly imprinted film at polypyrrole sulfonated graphene/hyaluronic acid-multiwalled carbon nanotubes modified electrode for determination of tryptamine. AB - An imprinted electrochemical sensor based on polypyrrole-sulfonated graphene (PPy SG)/hyaluronic acid-multiwalled carbon nanotubes (HA-MWCNTs) for sensitive detection of tryptamine was presented. Molecularly imprinted polymers (MIPs) were synthesized by electropolymerization using tryptamine as the template, and para aminobenzoic acid (pABA) as the monomer. The surface feature of the modified electrode was characterized by cyclic voltammetry (CV). The proposed sensor was tested by chronoamperometry. Several important parameters controlling the performance of the molecularly imprinted sensor were investigated and optimized. The results showed that the PPy-SG composites films showed improved conductivity and electrochemical performances. HA-MWCNTs bionanocomposites could enhance the current response evidently. The good selectivity of the sensor allowed three discriminations of tryptamine from interferents, which include tyramine, dopamine and tryptophan. Under the optimal conditions, a linear ranging from 9.0*10(-8) mol L(-1) to 7.0*10(-5) mol L(-1) for the detection of tryptamine was observed with the detection limit of 7.4*10(-8) mol L(-1) (S/N=3). This imprinted electrochemical sensor was successfully employed to detect tryptamine in real samples. PMID- 22074811 TI - The role of neuromodulators in selective attention. AB - Several classes of neurotransmitters exert modulatory effects on a broad and diverse population of neurons throughout the brain. Some of these neuromodulators, especially acetylcholine and dopamine, have long been implicated in the neural control of selective attention. We review recent evidence and evolving ideas about the importance of these neuromodulatory systems in attention, particularly visual selective attention. We conclude that, although our understanding of their role in the neural circuitry of selective attention remains rudimentary, recent research has begun to suggest unique contributions of neuromodulators to different forms of attention, such as bottom-up and top-down attention. PMID- 22074812 TI - Characterizing longitudinal patterns of physical activity in mid-adulthood using latent class analysis: results from a prospective cohort study. AB - The authors aimed to describe how longitudinal patterns of physical activity during mid-adulthood (ages 31-53 years) can be characterized using latent class analysis in a population-based birth cohort study, the Medical Research Council's 1946 National Survey of Health and Development. Three different types of physical activity-walking, cycling, and leisure-time physical activity-were analyzed separately using self-reported data collected from questionnaires between 1977 and 1999; 3,847 study members were included in the analysis for one or more types of activity. Patterns of activity differed by sex, so stratified analyses were conducted. Two walking latent classes were identified representing low (52.8% of males in the cohort, 33.5% of females) and high (47.2%, 66.5%) levels of activity. Similar low (91.4%, 82.1%) and high (8.6%, 17.9%) classes were found for cycling, while 3 classes were identified for leisure-time physical activity: "low activity" (46.2%, 48.2%), "sports and leisure activity" (31.0%, 35.3%), and "gardening and do-it-yourself activities" (22.8%, 16.5%). The classes were reasonably or very well separated, with the exception of walking in females. Latent class analysis was found to be a useful tool for characterizing longitudinal patterns of physical activity, even when the measurement instrument differs slightly across ages, which added value in comparison with observed activity at a single age. PMID- 22074814 TI - Relationship between the level of antibodies in bulk tank milk and the within herd seroprevalence of Coxiella burnetii in cows. AB - The relationship between the level of antibodies in bulk tank milk (BTM) and the within-herd seroprevalence of Coxiella burnetii in cows was assessed. Blood from milking cows and BTM were sampled in 55 infected herds and tested using commercial enzyme-linked immunosorbent assay (ELISA) kits. The relationship between antibody levels and WHP, which was quantified using a general linear model, was only moderate (R(2)=0.15). Nevertheless, the lowest antibody level in BTM was associated with the lowest mean within-herd prevalence. The present finding indicates that ELISA applied to BTM could identify infected herds with quite low within-herd seroprevalence. For such herds, the vaccination of dairy cows as well as nulliparous heifers using a phase I vaccine could effectively prevent C. burnetii shedding. PMID- 22074813 TI - The treatment of severe child aggression (TOSCA) study: Design challenges. AB - BACKGROUND: Polypharmacy (the concurrent use of more than one psychoactive drug) and other combination interventions are increasingly common for treatment of severe psychiatric problems only partly responsive to monotherapy. This practice and research on it raise scientific, clinical, and ethical issues such as additive side effects, interactions, threshold for adding second drug, appropriate target measures, and (for studies) timing of randomization. One challenging area for treatment is severe child aggression. Commonly-used medications, often in combination, include psychostimulants, antipsychotics, mood stabilizers, and alpha-2 agonists, which vary considerably in terms of perceived safety and efficacy. RESULTS: In designing our NIMH-funded trial of polypharmacy, we focused attention on the added benefit of a second drug (risperidone) to the effect of the first (stimulant). We selected these two drugs because their associated adverse events might neutralize each other (e.g., sleep delay and appetite decrease from stimulant versus sedation and appetite increase from antipsychotic). Moreover, there was considerable evidence of efficacy for each drug individually for the management of ADHD and child aggression. The study sample comprised children (ages 6-12 years) with both diagnosed ADHD and disruptive behavior disorder (oppositional-defiant or conduct disorder) accompanied by severe physical aggression. In a staged sequence, the medication with the least problematic adverse effects (stimulant) was openly titrated in 3 weeks to optimal effect. Participants whose behavioral symptoms were not normalized received additional double-blind medication, either risperidone or placebo, by random assignment. Thus children whose behavioral symptoms were normalized with stimulant medication were not exposed to an antipsychotic. All families participated in an empirically-supported parent training program for disruptive behavior, so that the actual comparison was stimulant+parent training versus stimulant+antipsychotic+parent training. CONCLUSIONS: We hope that the resolutions of the challenges presented here will be useful to other investigators and facilitate much-needed research on child psychiatric polypharmacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00796302. PMID- 22074815 TI - Theoretical validation on the existence of two transverse surface waves in piezoelectric/elastic layered structures. AB - In this paper, we analytically study the dispersion behavior of transverse surface waves in a piezoelectric coupled solid consisting of a transversely isotropic piezoelectric ceramic layer and an isotropic metal or dielectric substrate. This study is a revisit to the stiffened Love wave propagation done previously. Closed-form dispersion equations are obtained in a very simple mathematical form for both electrically open and shorted cases. From the viewpoint of physical situation, two transverse surface waves (i.e., the stiffened Love wave and the FDLW-type wave) are separately found in a PZT-4/steel system and a PZT-4/zinc system. All the observed dispersion curves are theoretically validated through the discussion on the limit values of phase velocity using the obtained dispersion equations. Those validation and discussion give rise to a deeper understanding on the existence of transverse surface waves in such piezoelectric coupled structures. The results can be used as a benchmark for the study of the wave propagation in the piezoelectric coupled structures and are significant in the design of wave propagation in the piezoelectric coupled structures as well. PMID- 22074817 TI - Large procyanidins prevent bile-acid-induced oxidant production and membrane initiated ERK1/2, p38, and Akt activation in Caco-2 cells. AB - Procyanidins are oligomers of flavanol subunits present in large amounts in fruits and vegetables. Their consumption is associated with health benefits against colonic inflammation and colorectal cancer (CRC). Large procyanidins (with more than three subunits) are not absorbed by intestinal epithelial cells but could exert biological actions through their interactions with the cell membrane. This study investigated the capacity of hexameric procyanidins (Hex) to prevent oncogenic events initiated by deoxycholic acid (DCA), a secondary bile acid linked to the promotion of CRC. Hex interacted with Caco-2 cell membranes preferentially at the water-lipid interface. Hex (2.5-20 MUM) inhibited DCA triggered increase in cellular calcium, NADPH oxidase activation, and oxidant production. DCA promoted the activation of protein kinase B (Akt), of the mitogen activated protein kinases ERK1/2 and p38, and of the downstream transcription factor AP-1. This activation was not triggered by calcium or oxidant increases. Hex caused a dose-dependent inhibition of DCA-mediated activation of all these signals. DCA also triggered alterations in the cell monolayer morphology and apoptotic cell death, events that were delayed by Hex. The capacity of large procyanidins to interact with the cell membrane and prevent those cell membrane associated events can in part explain the beneficial effects of procyanidins on CRC. PMID- 22074816 TI - [Early invasive strategy in non-ST-segment elevation acute coronary syndrome. The paradox continues]. AB - OBJECTIVE: Observational studies have reported a paradoxical inverse relationship between the use of an early invasive strategy (EIS) and the risk of events in patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS). The study objectives are: 1) to examine the association between baseline risk in patients with NSTE ACS and the use of EIS; and 2) to identify some of the factors independently associated to the use of EIS. DESIGN: Retrospective cohort study. SETTING: Intensive care units participating in the SEMICYUC ARIAM Registry. PATIENTS: Consecutive patients admitted with a diagnosis of NSTE-ACS within 48 hours of evolution between the months of April-July 2010. INTERVENTIONS: None. MAIN OUTCOMES: Coronary angiography with or without angioplasty within 72 hours, risk stratification using the GRACE scale. RESULTS: We analyzed 543 patients with NSTE-ACS, of which 194 were of low risk, 170 intermediate risk and 179 high risk. The EIS was used in 62.4% of the patients at low risk, in 60.2% of those with intermediate risk, and in 49.7% of those at high risk (p for tendency 0.0144). The EIS was used preferentially in patients with low severity and comorbidity. In the logistic regression model, EIS was independently associated to the availability of a catheterization laboratory (OR 2.22 [CI 95% 1.55 to 3.19]), the presence of ST changes on ECG (OR 1.80 [1.23 to 2.64]), or the existence of a low risk of bleeding (OR 0.76 [0.66 to 0.88)]. Conversely, EIS was less prevalent in patients with diabetes (OR 0.60 [0.41 to 0.88]) or tachycardia upon admission (OR 0.54 [0 36 to 0.82]). CONCLUSIONS: In 2010 there remained a lesser relative use of EIS in patients at high risk, due in part to an increased risk of bleeding in these patients. PMID- 22074818 TI - Validation of an air-puff passive-avoidance paradigm for assessment of aversive learning and memory in rat models of chronic pain. AB - Chronic pain is associated with cognitive deficits. Considerable overlap in brain regions involved in pain and aversion suggests that aversive learning and memory may be affected during chronic pain. Passive-avoidance paradigms traditionally use foot-shock to induce context-conditioned avoidance and may be unsuitable for use in animal models of chronic pain, which are commonly associated with hypersensitivity of the hind-paws. The aim of the present study was to develop and validate a novel passive-avoidance paradigm in rats, employing air-puff as the aversive stimulus, and to use this paradigm to assess aversive learning and memory in rat models of chronic inflammatory and neuropathic pain. Air-puff exposure produced a significant passive-avoidance and this response was attenuated following administration of scopolamine. Nerve-ligated rats and rats injected with complete Freund's adjuvant developed allodynia and hyperalgesia. Air-puff produced a significant passive-avoidance response in both chronic pain models. However, there was no difference in the response between either model and its respective control group. Thus, air-puff can be used as an alternative to foot-shock to induce a passive-avoidance response. The data generated using this model suggest that aversive learning and memory remain intact in the rat spinal nerve ligation and complete Freund's adjuvant models of chronic neuropathic and inflammatory pain, respectively. PMID- 22074819 TI - Lipschitz-Killing curvature based expected Euler characteristics for p-value correction in fNIRS. AB - Functional near-infrared spectroscopy (fNIRS) is a non-invasive imaging approach for measuring brain activities based on changes in the cerebral concentrations of hemoglobin. Recently, statistical analysis based on a general linear model (GLM) has become popular. Here, to impose statistical significance on the activation detected by fNIRS, family-wise error (FWE) rate control is important. However, unlike fMRI, in which measurements are densely sampled on a regular lattice and Gaussian smoothing makes the resulting random field homogeneous, the random fields from fNIRS are inhomogeneous due to the interpolation from sparsely and irregularly distributed optode locations. Thus, tube formula based correction has been proposed to address this issue. However, Sun's tube formula cannot be used for general random fields such as F-statistics. To overcome these difficulties, we employ the expected Euler characteristic approach based on Lipschitz-Killing curvature (LKC) to control the family-wise error rate. We compared this correction method with Sun's tube formula for t-statistics to confirm the existing method. Based on this comparison, we show that covariance estimation should be modified to consider channel-wise least-square residual correlation. These new results supplement the existing tool of statistical parameter mapping for fNIRS. PMID- 22074820 TI - Proteasome inhibitors induce apoptosis and reduce viral replication in primary effusion lymphoma cells. AB - Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV). This study provides evidence that proteasomal activity is required for both survival of PEL cells stably harboring the KSHV genome and viral replication of KSHV. We evaluated the cytotoxic effects of proteasome inhibitors on PEL cells. The proteasome inhibitors MG132, lactacystin, and proteasome inhibitor I dramatically inhibited cell proliferation and induced apoptosis of PEL cells through the accumulation of p21 and p27. Furthermore, proteasome inhibitors induced the stabilization of NF-kappaB inhibitory molecule (IkappaBalpha) and suppressed the transcriptional activity of NF-kappaB in PEL cells. The NF-kappaB specific inhibitor BAY11-7082 also induced apoptosis in PEL cells. The constitutive activation of NF-kappaB signaling is essential for the survival and growth of B cell lymphoma cells, including PEL cells. NF-kappaB signaling is upregulated by proteasome-dependent degradation of IkappaBalpha. The suppression of NF-kappaB signaling by proteasome inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, proteasome activity is required for KSHV replication in KSHV latently infected PEL cells. MG132 reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. These findings suggest that proteasome inhibitors may represent a novel strategy for the treatment of KSHV infection and KSHV-associated lymphomas. PMID- 22074821 TI - Induction of antigen-specific immunity by pH-sensitive carbonate apatite as a potent vaccine carrier. AB - The ability of carbonate apatite (CO(3)Ap) to enhance antigen-specific immunity was examined in vitro and in vivo to investigate its utility as a vaccine carrier. Murine bone marrow-derived dendritic cells took up ovalbumin (OVA) containing CO(3)Ap more effectively than free OVA. Interestingly, mice immunized with OVA-containing CO(3)Ap produced OVA-specific antibodies more effectively than mice immunized with free OVA. Furthermore, immunization of C57BL/6 mice with OVA-containing CO(3)Ap induced the proliferation and antigen-specific production of IFN-gamma by splenocytes more strongly than immunization with free OVA. Moreover, no significant differences were detected in the induction of delayed type hypersensitivity responses, an immune reaction involving an antigen specific, cell-mediated immune response between OVA-containing CO(3)Ap and OVA containing alumina salt (Alum), suggesting that CO(3)Ap induced cell-mediated immune response to the same degree as Alum, which is commonly used for clinical applications. This study is the first to demonstrate the induction of antigen specific immune responses in vivo by CO(3)Ap. PMID- 22074822 TI - Effects of micropatterned curvature on the motility and mechanical properties of airway smooth muscle cells. AB - Geometric features such as size and shape of the microenvironment are known to alter cell behaviors such as growth, differentiation, apoptosis, and migration. Little is known, however, about the effect of curvature on cell behaviors despite that many cells reside in curved space of tubular organs such as the bronchial airways. To address this question, we fabricated micropatterned strips that mimic airway walls with varying curvature. Then, we cultured airway smooth muscle cells (ASMCs) on these strips and investigated the cells' motility and mechanical properties using time-lapse imaging microscopy and optical magnetic twisting cytometry (OMTC). We found that both motility and mechanical properties of the ASMCs were influenced by the curvature. In particular, when the curvature increased from 0 to 1/150 MUm(-1), the velocity of cell migration first decreased (0-1/750 MUm(-1)), and then increased (1/750-1/150 MUm(-1)). In contrast, the cell stiffness increased and then decreased. Thus, at the intermediate curvature (1/750 MUm(-1)) the ASMCs were the least motile, but most stiff. The contractility instead decreased consistently as the curvature increased. The level of F-actin, and vinculin expression within the ASMCs appeared to correlate with the contractility and motility, respectively, in relation to the curvature. These results may provide valuable insights to understanding the heterogeneity of airway constrictions in asthma as well as the developing and functioning of other tubular organs and tissue engineering. PMID- 22074823 TI - STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH+/CD133+ stem cell-like human colon cancer cells. AB - Persistent activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in colon cancer. Increasing evidence suggests the existence of a small population of colon cancer stem or cancer-initiating cells may be responsible for tumor initiation, metastasis, and resistance to chemotherapy and radiation. Whether STAT3 plays a role in colon cancer-initiating cells and the effect of STAT3 inhibition is still unknown. Flow cytometry was used to isolate colon cancer stem-like cells from three independent human colon cancer cell lines characterized by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulation (ALDH(+)/CD133(+)). The effects of STAT3 inhibition in colon cancer stem-like cells were examined. The phosphorylated or activated form of STAT3 was expressed in colon cancer stem-like cells and was reduced by a STAT3-selective small molecular inhibitor, FLLL32. FLLL32 also inhibited the expression of potential STAT3 downstream target genes in colon cancer stem-like cells including survivin, Bcl-XL, as well as Notch-1, -3, and 4, which may be involved in stem cell function. Furthermore, FLLL32 inhibited cell viability and tumorsphere formation as well as induced cleaved caspase-3 in colon cancer stem-like cells. FLLL32 is more potent than curcumin as evidenced with lower IC50 in colon cancer stem-like cells. In summary, our results indicate that STAT3 is a novel therapeutic target in colon cancer stem-like cells and inhibition of STAT3 in cancer stem-like cells may offer a potential treatment for colorectal cancer. PMID- 22074824 TI - Silencing p110beta prevents rapid depletion of nuclear pAkt. AB - The p110beta subunit in the class IA PI3K family may act as an oncogene and is critical for prostate tumor development in PTEN knockout mice. We tested the possible involvement of p110beta in a recently described rapid depletion of phosphorylated Akt (pAkt) in the nucleus. Previous work showed that this down regulation is induced by extracellular ATP or by statins and is mediated by the purinergic receptor P2X7. Here, we used p110beta knock out mouse embryonic fibroblasts (MEFs) and siRNA-treated cancer cells. We found that p110beta is essential for ATP- or statin-induced nuclear pAkt depletion in MEFs and in several cancer cell lines including prostate cancer cells. ATP, statin or the selective P2X7 agonist BzATP also inhibited cell growth, and this inhibition was not seen in p110beta knock out cells. We also found that p110beta was necessary for statin-induced changes in binding between FKBP51, pAkt and PTEN. Our data show that p110beta is essential for the ATP- and statin-induced effects and support a role of nuclear pAkt in cancer development. They also provide support for a chemopreventive effect of statins mediated by depletion of nuclear pAkt. PMID- 22074825 TI - IRS-2 deficiency in macrophages promotes their accumulation in the vascular wall. AB - The aim of this study was to investigate the role of insulin receptor substrate-2 (IRS-2) mediated signal in macrophages on the accumulation of macrophages in the vascular wall. Mice transplanted with IRS-2(-/-) bone marrow, a model of myeloid cell restricted defect of IRS-2, showed accumulation of monocyte chemoattractant protein-1-expressing macrophages in the vascular wall. Experiments using cultured peritoneal macrophages showed that IRS-2-mediated signal pathway stimulated by physiological concentrations of insulin, not by IL-4, contributed to the suppression of monocyte chemoattractant protein-1 expression induced by lipopolysaccharide. Our data indicated that IRS-2 deficiency in macrophages enhanced their accumulation in the vascular wall accompanied by increased expression of proinflammatory mediators in macrophages. These results suggest a role for insulin resistance in macrophages in early atherosclerogenesis. PMID- 22074826 TI - Differential activation of cAMP- and cGMP-dependent protein kinases by cyclic purine and pyrimidine nucleotides. AB - The cyclic purine nucleotides cAMP and cGMP are well-characterized second messengers and activators of PKA and PKG, respectively. In contrast, the functions of the cyclic pyrimidine nucleotides cCMP and cUMP are poorly understood. cCMP induces relaxation of smooth muscle via PKGI, and phosphodiesterases differentially hydrolyze cNMPs. Here, we report that cNMPs differentially activate PKA isoforms and PKGIalpha. The combination of cCMP with cAMP reduced the EC(50) of cAMP for PKA. PKGIalpha exhibited higher specificity for the cognate cNMP than PKA. Our data support a role of cCMP and cUMP as second messengers. PMID- 22074827 TI - Role of ubiquitination in PCSK9-mediated low-density lipoprotein receptor degradation. AB - The proprotein convertases subtilisin kexin 9 (PCSK9) binds to the epidermal growth factor domain A (EGF-A) of low-density lipoprotein receptor (LDLR) and leads to its destruction. However, the intracellular processes leading to LDLR degradation have not been fully delineated. In this report, we show that PCSK9 treatment can lead to ubiquitination of LDLR, which was enhanced in the presence of proteasome inhibitor MG132. Furthermore, LDLR protein carrying mutations in the C-terminal ubiquitination sites was resistant to PCSK9-mediated degradation. Our data suggest that the ubiquitination system is involved in PCSK9-induced LDLR degradation. PMID- 22074828 TI - Flavonoids inhibit high glucose-induced up-regulation of ICAM-1 via the p38 MAPK pathway in human vein endothelial cells. AB - Recently, several flavonoids have been shown to have cardioprotective, cancer preventive, or anti-inflammatory properties. However, the specific mechanisms underlying their protective effects remain unclear. We aimed to investigate the different effects of three representative flavonoids-hesperidin, naringin, and resveratrol-on intracellular adhesion molecule-1 (ICAM-1) induction in human umbilical vein endothelial cells (HUVECs) by using high-glucose (HG) concentrations and the possible underlying molecular mechanisms. In HG-induced HUVEC cultures, the effects of three different flavonoids on ICAM-1 production and p38 phosphorylation were examined in the presence or absence of inhibitors targeting the mitogen-activated protein kinase (MAPK) signal transduction pathway. HG stimulation of HUVECs increased the levels of the adhesion molecules ICAM-1 and endothelial selectin (E-selectin). Pretreatment with all the three flavonoids drastically inhibited ICAM-1 expression in a time-dependent manner, but did not alter VCAM-1 and E-selectin expressions. Moreover, we investigated the effects of flavonoids on the MAPK signal transduction pathway, because MAPK families are associated with vascular inflammation under stress. These flavonoids did not block HG-induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but completely inhibited the HG-induced phosphorylation of p38 MAPK. SB202190, an inhibitor of p38 MAPK, also inhibited the HG-induced enrichment of ICAM-1. This study demonstrated that hesperidin, naringin, and resveratrol reduced the HG-induced ICAM-1 expression via the p38 MAPK signaling pathway, contributing to the inhibition of monocyte adhesion to endothelial cells. PMID- 22074829 TI - Lysophosphatidylcholine enhances the suppressive function of human naturally occurring regulatory T cells through TGF-beta production. AB - Naturally occurring CD4(+)CD25(+) regulatory T cells (nTregs) play a pivotal role in the maintenance of self-tolerance and immune homeostasis. To gain insight into the mechanism of action of nTregs in pathological and physiological immune responses, it is important to analyze bioactive molecules that modulate the maintenance and function of nTregs. From a library of bioactive lipids, we obtained lysophosphatidylcholine (LPC) as a molecule that enhanced the Foxp3 expression and suppressive function of human nTregs significantly in comparison with those of DMSO-treated nTregs (control). The expression levels of TGF-beta1 mRNA and protein in LPC-treated nTregs were significantly higher than those in control nTregs. After treatment with anti-TGF-beta1 antibody, the increases in Foxp3 expression and the suppressive properties of LPC-treated nTregs returned to the levels observed in control nTregs. These findings indicate that LPC enhances Foxp3 expression and the suppressive function of nTregs through TGF-beta1 produced by nTregs themselves. Experimental knockdown of G2A and GPR4 showed that this LPC-induced TGF-beta1 expression in nTregs was due to G2A signaling, and did not involve GPR4. Moreover, JNK was a major contributor to LPC-induced TGF-beta1 expression in nTregs, although LPC activated MAPKs including ERK1/2, p38 MAPK, and JNK via G2A. LPC is a bioactive lysolipid highly abundant in the circulation. Therefore, LPC may contribute to the maintenance and function of human nTregs in vivo. PMID- 22074830 TI - Involvement of proton-sensing receptor TDAG8 in the anti-inflammatory actions of dexamethasone in peritoneal macrophages. AB - Dexamethasone (DEX), a potent glucocorticoid, increased the expression of T-cell death associated gene 8 (TDAG8), a proton-sensing G protein-coupled receptor, which is associated with the enhancement of acidic pH-induced cAMP accumulation, in peritoneal macrophages. We explored the role of increased TDAG8 expression in the anti-inflammatory actions of DEX. The treatment of macrophages with either DEX or acidic pH induced the cell death of macrophages; however, the cell death was not affected by TDAG8 deficiency. While DEX inhibited lipopolysaccharide induced production of tumor necrosis factor-alpha, an inflammatory cytokine, which was independent of TDAG8, at neutral pH, the glucocorticoid enhanced the acidic pH-induced inhibition of tumor necrosis factor-alpha production in a manner dependent on TDAG8. In conclusion, the DEX-induced increase in TDAG8 expression is in part involved in the glucocorticoid-induced anti-inflammatory actions through the inhibition of inflammatory cytokine production under the acidic pH environment. On the other hand, the role of TDAG8 in the DEX-induced cell death is questionable. PMID- 22074832 TI - Mixed dentition space analysis for a northern Italian population: new regression equations for unerupted teeth. AB - OBJECTIVE: The aim of this study was to determine linear regression equations for a Northern Italian population to predict mandibular permanent premolars and canines widths, and particularly, second premolar widths, using the sum of the widths of the four mandibular incisors, canines and first premolars. MATERIALS AND METHODS: Mesiodistal tooth widths were measured from 230 dental casts obtained from Northern Italian patients (130 females and 100 males). Student's t test or Wilcoxon test for independent and paired samples were used to determine right/left side and male/female differences. Correlation coefficients and linear regression equations were constructed to evaluate the relationship between 1) the combined mesiodistal widths of the permanent mandibular incisors (independent variable) and the combined mesiodistal widths of the canine and premolars (dependent variable); 2) the combined mesiodistal widths of the incisors, canines and first premolars (independent variable) and the widths of the second premolars (dependent variable). Significance value was set a priori at 0.05. RESULTS: A linear regression equation was found, y=0.585x+7.927 (r=0.734) considering right and left sides of mandibular arch together, to predict canines and premolars widths. For second premolar width, the linear regression equation was y=0.201x+2.149 (r=0.641), even when considering the right and left sides of the mandibular arch together. CONCLUSIONS: New regression equations were derived for a Northern Italian population. PMID- 22074833 TI - Dentition phase and chronological age in relation to gingival crevicular fluid alkaline phosphatase activity in growing subjects. AB - OBJECTIVE: Identification of skeletal maturation phases is of primary importance in terms of individual responsiveness to nearly all dentofacial orthopaedic treatments. In this regard, dentition phase and chronological age are still widely used to define the timing of and responsiveness to orthodontic treatments. Recently, gingival crevicular fluid (GCF) alkaline phosphatase (ALP) activity has been shown to be a reliable biomarker of skeletal maturation in growing subjects. Here, for the first time, circumpubertal dentition phases and chronological age were evaluated for correlations with GCF ALP activity, as a biomarker of skeletal maturation. MATERIALS AND METHODS: Eighty-five healthy growing subjects (51 females, 34 males; mean age, 11.7+/-2.3 years) were enrolled into this double blind, prospective, cross-sectional-design study. Samples of GCF were collected from each subject at the mesial and distal sites of both of the central incisors, at the maxillary and mandibular arches. Their dentition phases were recorded as intermediate mixed, late mixed, or permanent. GCF ALP enzymatic activity was determined spectrophotometrically. RESULTS: The dentition phases showed median GCF ALP activities from 42.0 to 67.5 mU/sample. Although these were slightly greater for the permanent dentition, no significant differences were seen. Also, the chronological age did not correlate significantly with GCF ALP activity, and no significant differences were seen between maxillary and mandibular sites in any of the comparisons. CONCLUSIONS: Assessment for treatment timing of dentofacial disharmonies in individual patients that require monitoring of their skeletal maturation phases should not rely on their circumpubertal dentition phase and chronological age. PMID- 22074834 TI - Mesial rotation of upper first molars in Class II division 1 malocclusion in the mixed dentition: a controlled blind study. AB - OBJECTIVE: To compare the amount of upper molar rotation in subjects with Class II Division 1 malocclusion and subjects with normal occlusion in the intermediate and late mixed dentition phases. MATERIALS AND METHODS: Dental cast measurements were performed in a sample of 120 Class II Division 1 subjects (CL2 group, 67 females and 53 males, mean age 9.4+/-1.1 years), and in a sample of 58 Class I subjects (CL1 group, 34 females and 24 males, mean age 9.7+/-1.2 years). Independent sample t tests were used for statistical comparisons (P<.05). RESULTS: The amount of upper molar rotation was significantly greater in CL2 group when compared with CL1 group as assessed by both the mesial and buccal molar cusp angles. No differences were found with regard to upper or lower arch depths, or upper intercanine width. CL2 group showed a significant deficiency in upper intermolar width along with a significant posterior transverse interarch discrepancy when compared with CL1 group. CONCLUSIONS: Subjects with Class II malocclusion in the mixed dentition present with mesial upper molar rotation in about 84% of the cases. The correction of molar rotation may provide between 1 and 2mm of gain in arch perimeter and of improvement in molar relationships per side in 5 out 6 Class II patients. PMID- 22074835 TI - Malocclusions and non-nutritive sucking habits: a preliminary study. AB - OBJECTIVE: This study investigated the non-nutritive sucking habits in a sample of patients with malocclusions at the Unit of Pediatric Dentistry of the "Sapienza", University of Rome. MATERIALS AND METHODS: 81 children (average age 5.9 years) were examined from January to December 2008. All children showed typical malocclusions that could be associated with non-nutritive sucking habits (pacifier or finger). Increased overjet (OVJ), anterior openbite (OPB), and posterior crossbite (CRB) were recorded in this survey. A questionnaire was directed to parents. RESULTS: At the first examination 40.4% of pacifier users over 24 months were affected by an anterior OPB, 50% by a posterior CRB and 39.4% by an increased OVJ. Moreover, 40.4% of the children with finger or thumb sucking behavior were affected by an anterior OPB, 29.2% by a posterior CRB, and 42.4% by an increased OVJ. CONCLUSIONS: No statistically significant associations could be detected between the non-nutritive sucking habits and the malocclusions. There was no difference in type of habit in children who presented an anterior OPB, while there was a higher prevalence rate of children with a posterior CRB who had sucked the pacifier and of children with increased OVJ who had sucked their finger. PMID- 22074836 TI - Spontaneous eruption of impacted second molars. AB - OBJECTIVES: To propose a treatment protocol for the management of impacted second molars. MATERIALS AND METHODS: Patients were randomly divided into two equal groups (20 patients in each). The patients in the first group underwent a surgical removal of the mucosa covering retained teeth; the second group was the control group and patients were not treated but only observed. The total number of retained teeth considered were 66 (34 in the first group and 32 in the control group). A Chi squared test has been performed to compare the prevalence of eruption in the two groups. We compared the frequency of eruption for the treatment compared to the control group by calculating the risk ratio (RR) and 95% confidence interval (95% CI). RESULTS: Eruption occurred in 32 teeth after surgical removal of the mucosa while in the control group only 3 teeth erupted in the considered period. The difference between the two groups showed statistically significant. Among the non erupted teeth, 20 were positioned with a mesial inclination and 12 were positioned vertically. CONCLUSIONS: The results show that the removal of the mucosa covering teeth allows in several cases second molars to erupt. It's a conservative method which doesn't exclude the possibility of a successive different therapy. Therefore it must be considered among the treatment options during treatment planning. PMID- 22074837 TI - Saliva analysis by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) in orthodontic treatment: first pilot study. AB - OBJECTIVE: SELDI-TOF-MS (Surface-Enhanced Laser Desorption/Ionization Time-Of Flight Mass Spectrometry) allows the generation of an accurate protein profile from minimal amounts of biological samples and may executes proteomic profile of saliva. The aim of this work is to compare the proteomic profile of saliva of patients in orthodontic treatment to the beginning of treatment and after three months by using the surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. MATERIALS AND METHODS: Saliva was collected from 14 patients, between the 11 and 17 years, to the beginning of the orthodontic treatment and after three months. Specimens were centrifuged (10 min, 13000 x g); the Q10 ProteinChips were prepared according to the manufacturer's instructions and were loaded with the supernatants. A saturated solution of sinapinic acid was used as energy-absorbing matrix. The analysis was performed in a m/z range from 2500 to 25000 Da, and the proteomic profiles were compared by a specific data analysis software. Saliva (5 mL) was collected by spitting directly into a clean 15 mL conical tube. The samples were then aliquotted and stored at 80 degrees C until use. RESULTS: Profile of saliva of patients before orthodontic treatment present a number of peaks different respect profile of saliva after three months of treatment. The average intensities of peaks at m/z 3372, 5232, 4045 and 10128 were significantly higher after three months then at beginning of treatment in the same patients and among these one. The Roc Plot has demonstrated high sensitivity and specificity. CONCLUSIONS: Many differences were noted in salivary proteomic profile obtained using the SELDI-TOF-MS technology in patients in orthodontic treatment to beginning and after three months. These data suggest that the proteomic analysis of saliva is a promising new tool for a non-invasive study of oral mucosa and bone changes. PMID- 22074838 TI - An insight into four orthodontic treatment need indices. AB - Occlusal indices have been introduced and used to rank or categorize the occlusion. According to Dr. William Shaw and colleagues (1995), there are five types of occlusal indices, diagnostic, epidemiologic, orthodontic treatment need, orthodontic treatment outcome, and treatment complexity indices. Orthodontic treatment need indices are used to rank the malocclusion. They were devised to minimize the subjectivity associated with the diagnosis, referral and complexity assessment of malocclusion. Some are also multifunctional and used to assess the outcome of orthodontic treatment. The overall aim of the present article is to provide an overview on four commonly used American and European orthodontic treatment need indices, review their modifications, advantages, and limitations. These indices are the Index of Orthodontic Treatment Need (IOTN), the Dental Aesthetic Index (DAI), the Handicapping Labio-Lingual Deviation index (HLD), and the Index of Complexity, Outcome and Need (ICON). PMID- 22074839 TI - Psychological aspects of orthodontics in clinical practice. Part one: treatment specific variables. AB - The orthodontist-patient relationship may have a significant impact on treatment outcome and patient satisfaction, thus improving the overall quality of care. Effective communication is crucial and unfortunately, it is often underestimated in a busy clinical practice. Aim of part one of this article is to review the psychological aspects that are relevant to a number of treatment variables in clinical orthodontics, including compliance with treatment, oral hygiene, management of orthodontic pain and discomfort, and oral habits. Due to the complex nature of the psychology of orthodontic treatment, it is difficult to determine the extent of the influence that the orthodontist-patient relationship may have on these variables, with effective communication and an awareness of the psychological issues playing an important role in enhancing the orthodontist patient relationship. PMID- 22074840 TI - The Herbst appliance updated. AB - The aim of this paper is to analyze the evolution that the Herbst appliance has experienced in the last 30 years. In particular the different designs proposed for the Herbst appliance are examined and the related differences in clinical management, indications, and treatment effects are also illustrated. The two major challenges in the clinical management of the Herbst appliance are represented by the choice of the type of stabilization and by the control of the proclination of the lower incisors. The use of acrylic splints presents a set of relevant advantages: the construction technique is simple, the appliance can be worn easily by the patients, and the height of the splint can be adjusted to the growth pattern. Moreover, the acrylic splint Herbst can be used to reposition the mandible in cases with temporomandibular disorders. As for the proclination of the lower incisors, an accurate assessment of the neuromuscular pattern of the individual patient before treatment can provide the clinician with reliable criteria to evaluate the risk for incisor proclination during Herbst therapy. PMID- 22074841 TI - When should orthodontics be part of reconstruction of a degenerating dentition? A case report. AB - The present case report aims to describe a typical situation of an adult patient seeing her dentist for replacement of a missing tooth, but also requiring information regarding the possibilities for a return to the original occlusion as perceived by the patient based on family photos. The importance of the communication regarding the consequences of blindly following the patient's demand for a replacement of a missing tooth compared to the treatment possibilities when involving orthodontics is stressed. The significance of maintaining a high information level in the undergraduate training regarding treatment possibilities is stressed. The logic in dividing the treatment into separate phases defined by the solution of specific problems is demonstrated and minimizes the chair time as well as the treatment time. PMID- 22074842 TI - Interdisciplinary treatment of Class III malocclusion: a case report. AB - The case report describes the multidisciplinary treatment of a 25-year-old male patient with a Class III malocclusion. Anterior and bilateral posterior crossbites were present. To correct the posterior crossbite a surgically assisted rapid maxillary expansion was performed. The significant three dimensional skeletal discrepancy was solved in a second phase with a surgical advancement of the maxilla. Functional and aesthetic occlusion in an improved facial profile was achieved with an interdisciplinary treatment that included orthodontic treatment, maxillofacial and periodontal surgery, and direct composite restorations. PMID- 22074843 TI - Indirect bonding with thermal glue and brackets with positioning jigs. AB - In orthodontics the precise location of bracket placement on the teeth is a goal in order to individualize and optimize treatment outcome. The authors will describe the indirect bonding procedure with thermal glue transfer tray and brackets with positioning jigs for precise bracket placement. PMID- 22074844 TI - Moderate/severe erectile dysfunction in patients with antiphospholipid syndrome. AB - PURPOSE: To evaluate sexual function of antiphospholipid syndrome (APS) patients using the Brazilian version of the validated International Index of Erectile Function (IIEF). MATERIALS AND METHODS: Eleven APS male patients (Sapporo criteria) were age and race-matched with 22 healthy controls. Demographic and clinical data, drug use and antiphospholipid antibodies were evaluated. The IIEF was also self-applied. RESULTS: Mean age (p = 0.114), frequency of Caucasian race (p = 1.00) and married status (p = 0.438) were similar in APS and controls. Mean disease duration was 8.8 +/- 4.6 years. Erectile dysfunction (ED) was frequently observed in APS versus controls (45.5 vs. 4.5%, p = 0.0096), especially moderate/severe ED (p = 0.0081). The total IIEF score (49.6 vs. 67.1, p = 0.019), erectile function (19.6 vs. 28.1, p = 0.005) and intercourse satisfaction (7.8 vs. 11.9, p = 0.009) were lower in patients than in controls. No differences were seen in orgasmic function (p = 0.114), sexual desire (p = 0.123) or overall satisfaction (p = 0.097) between the groups. The comparison between APS patients with ED (n = 5) and without ED (n = 6) revealed more arterial events in APS with ED (100 vs. 16.7%, p = 0.0152), and also longer disease duration (12 [7-16] vs. 5.5 [2-13] years, p = 0.031). A trend towards lower venous events (20 vs. 83.3%, p = 0.0801) and higher renal thrombotic microangiopathy (60% vs. 0, p = 0.0606) was observed in APS patients with ED. Demographics, clinical manifestations, smoking and antiphospholipid antibodies positivity were similar in both groups. CONCLUSION: To our knowledge, this was the first study that demonstrated moderate/severe ED in almost 50% of cases of a rare autoimmune disease. This alteration was linked to arterial events and longer disease duration. PMID- 22074845 TI - Antinuclear and antiphospholipid antibodies in patients with multiple sclerosis. AB - The prevalence of autoantibodies in multiple sclerosis (MS) patients and their clinical associations differ between various studies. This study investigated antiphospholipid and antinuclear antibodies in 85 patients with multiple sclerosis (MS) and clinically isolated syndrome (CIS) with regard to their association with demographic features, MS specific clinical features and symptoms of connective tissue diseases. Autoantibodies tested included antinuclear antibodies (ANA) with their specificities and anticardiolipin (aCL) and anti-beta 2-glycoprotein I (anti-beta2GPI) antibodies. Antinuclear antibodies were more prevalent in MS patients than in controls (63.5% vs. 3.3%; p < 0.01) and in 19% of patients specific antinuclear antibodies were detected. Anti-beta2GPI IgM antibodies were more frequent in MS patients than in the control group (20% vs. 3.3%; p < 0.05). The frequency of anticardiolipin antibodies did not differ between MS patients and controls. MS patients seropositive for ANA and extractable nuclear antigens (ENA) had significantly shorter disease duration than seronegative patients (p < 0.05) and a lower disability score (Expanded Disability Status Score; EDSS) (p < 0.05). Anti-beta2GPI antibodies were more frequent in patients with secondary progressive MS (SP-MS) and specific ANA antibodies were more frequent in patients with clinically isolated syndrome (CIS) (p < 0.05). The presence of autoantibodies was not associated with the predominant site of neurological involvement or the clinical features of connective tissue diseases. PMID- 22074846 TI - Interspecies interactions that result in Bacillus subtilis forming biofilms are mediated mainly by members of its own genus. AB - Many different systems of bacterial interactions have been described. However, relatively few studies have explored how interactions between different microorganisms might influence bacterial development. To explore such interspecies interactions, we focused on Bacillus subtilis, which characteristically develops into matrix-producing cannibals before entering sporulation. We investigated whether organisms from the natural environment of B. subtilis--the soil--were able to alter the development of B. subtilis. To test this possibility, we developed a coculture microcolony screen in which we used fluorescent reporters to identify soil bacteria able to induce matrix production in B. subtilis. Most of the bacteria that influence matrix production in B. subtilis are members of the genus Bacillus, suggesting that such interactions may be predominantly with close relatives. The interactions we observed were mediated via two different mechanisms. One resulted in increased expression of matrix genes via the activation of a sensor histidine kinase, KinD. The second was kinase independent and conceivably functions by altering the relative subpopulations of B. subtilis cell types by preferentially killing noncannibals. These two mechanisms were grouped according to the inducing strain's relatedness to B. subtilis. Our results suggest that bacteria preferentially alter their development in response to secreted molecules from closely related bacteria and do so using mechanisms that depend on the phylogenetic relatedness of the interacting bacteria. PMID- 22074847 TI - Structural basis for interaction between the conserved cell polarity proteins Inscuteable and Leu-Gly-Asn repeat-enriched protein (LGN). AB - Interaction between the mammalian cell polarity proteins mInsc (mammalian homologue of Inscuteable) and Leu-Gly-Asn repeat-enriched protein (LGN), as well as that between their respective Drosophila homologues Inscuteable and Partner of Inscuteable (Pins), plays crucial roles in mitotic spindle orientation, a process contributing to asymmetric cell division. Here, we report a crystal structure of the LGN-binding domain (LBD) of human mInsc complexed with the N-terminal tetratricopeptide repeat (TPR) motifs of human LGN at 2.6-A resolution. In the complex, mInsc-LBD adopts an elongated structure with three binding modules--an alpha-helix, an extended region, and a beta-sheet connected with a loop--that runs antiparallel to LGN along the concave surface of the superhelix formed by the TPRs. Structural analysis and structure-based mutagenesis define residues that are critical for mInsc-LGN association, and reveal that the activator of G protein signaling 3 (AGS3)-binding protein Frmpd1 [4.1/ezrin/radixin/moesin (FERM) and PSD-95/Dlg/ZO-1 (PDZ) domain-containing protein 1] and its relative Frmpd4 interact with LGN via a region homologous to a part of mInsc-LBD, whereas nuclear mitotic apparatus protein (NuMA) and the C terminus of LGN recognize the TPR domain in a manner different from that by mInsc. mInsc binds to LGN with the highest affinity (K(D) ~ 2.4 nM) and effectively replaces the Frmpd proteins, NuMA, and the LGN C terminus, suggesting the priority of mInsc in binding to LGN. We also demonstrate, using mutant proteins, that mInsc-LGN interaction is vital for stabilization of LGN and for intracellular localization of mInsc. PMID- 22074848 TI - Integration of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in blood culture diagnostics: a fast and effective approach. AB - Sepsis is a major cause of mortality in hospitalized patients worldwide, with lethality rates ranging from 30 to 70 %. Sepsis is caused by a variety of different pathogens, and rapid diagnosis is of outstanding importance, as early and adequate antimicrobial therapy correlates with positive clinical outcome. In recent years, matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometry (MS) fingerprinting has become a powerful tool in microbiological diagnostics. The direct identification of micro-organisms in a positive blood culture by MALDI-TOF MS can shorten the diagnostic procedure significantly. Therefore, the aim of the present study was to evaluate whether identification rates could be improved by using the new Sepsityper kit from Bruker Daltonics for direct isolation and identification of bacteria from positive blood cultures by MALDI-TOF MS compared with the use of conventional separator gel columns, and to integrate the MALDI-TOF MS-based identification method into the routine course of blood culture diagnostics in the setting of a microbiological laboratory at a university hospital in Germany. The identification of Gram-negative bacteria by MALDI-TOF MS was significantly better using the Sepsityper kit compared with a separator gel tube-based method (99 and 68 % correct identification, respectively). For Gram-positive bacteria, only 73 % were correctly identified by MALDI-TOF with the Sepsityper kit and 59 % with the separator gel tube assay. A major problem of both methods was the poor identification of Gram-positive grape-like clustered cocci. As differentiation of Staphylococcus aureus from coagulase-negative staphylococci is of clinical importance, a PCR was additionally established that was capable of identifying S. aureus directly from positive blood cultures, thus closing this diagnostic gap. Another benefit of the PCR approach is the possibility of directly detecting the genes responsible for meticillin resistance in staphylococci and for vancomycin resistance in enterococci, which is of high importance for early adequate treatment. Both of the described methods were finally integrated into a protocol for fast and effective identification of bacteria from positive blood cultures. PMID- 22074849 TI - Streptococcus constellatus-associated pyoderma in a dog. AB - This report describes a case of chronic and deep pyodermitis in a 4-year-old male dog with a 3-month skin problems history that had been treated unsuccessfully with fluoroquinolone therapy, prescribed by a private medical veterinary practice, without an early diagnosis. Microbiological examination and antimicrobial susceptibility testing were performed in our laboratory (Faculty of Veterinary Medicine) and a diagnosis of Streptococcus constellatus-associated pyoderma in the dog was made. A new antimicrobial treatment, with tetracyclines, was designed after the definitive diagnosis and antimicrobial susceptibility testing performed by the Kirby-Bauer disc diffusion method. The dog remained free of clinical illness at completion of therapy. To our knowledge, this is the first case of a canine pyoderma caused by S. constellatus, a commensal organism which may also cause pyogenic infections. Furthermore, this study confirms that a fluoroquinolone represents a poor empirical choice for initial therapy of canine pyoderma. PMID- 22074850 TI - Influence of capsule size on the in vitro activity of antifungal agents against clinical Cryptococcus neoformans var. grubii strains. AB - Cryptococcosis causes disseminated disease in AIDS patients. In contrast to what occurs in laboratory conditions, a large capsule is produced by Cryptococcus neoformans in vivo during infection. The aim of this study was to compare the in vitro activity of different antifungal agents against 34 clinical isolates of C. neoformans var. grubii without or with capsule induction (CLSI, CLSI-C, respectively), following the CLSI M27A3 document. Capsule induction was obtained by addition of NaHCO(3) and incubation with CO(2). The geometric means of the MICs, in ug ml(-1), for CLSI and CLSI-C cultures, respectively, were 1.9 and 9.8 for fluconazole; 0.04 and 0.08 for itraconazole; 0.04 and 0.05 for voriconazole; 0.16 and 0.38 for amphotericin B; and 1.6 and 5.6 for 5-flucytosine. Thus fluconazole showed the highest MICs after capsule induction. Determination of antifungal activity after capsule induction may be clinically relevant and could be used to evaluate the correlation between in vitro results and clinical outcome. PMID- 22074851 TI - Functional outcomes of multi-condition collaborative care and successful ageing: results of randomised trial. AB - OBJECTIVE: To evaluate the effectiveness of integrated care for chronic physical diseases and depression in reducing disability and improving quality of life. DESIGN: A randomised controlled trial of multi-condition collaborative care for depression and poorly controlled diabetes and/or risk factors for coronary heart disease compared with usual care among middle aged and elderly people SETTING: Fourteen primary care clinics in Seattle, Washington. PARTICIPANTS: Patients with diabetes or coronary heart disease, or both, and blood pressure above 140/90 mm Hg, low density lipoprotein concentration >3.37 mmol/L, or glycated haemoglobin 8.5% or higher, and PHQ-9 depression scores of >= 10. INTERVENTION: A 12 month intervention to improve depression, glycaemic control, blood pressure, and lipid control by integrating a "treat to target" programme for diabetes and risk factors for coronary heart disease with collaborative care for depression. The intervention combined self management support, monitoring of disease control, and pharmacotherapy to control depression, hyperglycaemia, hypertension, and hyperlipidaemia. MAIN OUTCOME MEASURES: Social role disability (Sheehan disability scale), global quality of life rating, and World Health Organization disability assessment schedule (WHODAS-2) scales to measure disabilities in activities of daily living (mobility, self care, household maintenance). RESULTS: Of 214 patients enrolled (106 intervention and 108 usual care), disability and quality of life measures were obtained for 97 intervention patients at six months (92%) and 92 at 12 months (87%), and for 96 usual care patients at six months (89%) and 92 at 12 months (85%). Improvements from baseline on the Sheehan disability scale (-0.9, 95% confidence interval -1.5 to -0.2; P = 0.006) and global quality of life rating (0.7, 0.2 to 1.2; P = 0.005) were significantly greater at six and 12 months in patients in the intervention group. There was a trend toward greater improvement in disabilities in activities of daily living ( 1.5, -3.3 to 0.4; P = 0.10). CONCLUSIONS: Integrated care that covers chronic physical disease and comorbid depression can reduce social role disability and enhance global quality of life. Trial registration Clinical Trials NCT00468676. PMID- 22074852 TI - Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies. AB - OBJECTIVE: To investigate the association between intake of dietary fibre and whole grains and risk of colorectal cancer. DESIGN: Systematic review and meta analysis of prospective observational studies. DATA SOURCES: PubMed and several other databases up to December 2010 and the reference lists of studies included in the analysis as well as those listed in published meta-analyses. STUDY SELECTION: Prospective cohort and nested case-control studies of dietary fibre or whole grain intake and incidence of colorectal cancer. RESULTS: 25 prospective studies were included in the analysis. The summary relative risk of developing colorectal cancer for 10 g daily of total dietary fibre (16 studies) was 0.90 (95% confidence interval 0.86 to 0.94, I(2) = 0%), for fruit fibre (n = 9) was 0.93 (0.82 to 1.05, I(2) = 23%), for vegetable fibre (n = 9) was 0.98 (0.91 to 1.06, I(2) = 0%), for legume fibre (n = 4) was 0.62 (0.27 to 1.42, I(2) = 58%), and for cereal fibre (n = 8) was 0.90 (0.83 to 0.97, I(2) = 0%). The summary relative risk for an increment of three servings daily of whole grains (n = 6) was 0.83 (0.78 to 0.89, I(2) = 18%). CONCLUSION: A high intake of dietary fibre, in particular cereal fibre and whole grains, was associated with a reduced risk of colorectal cancer. Further studies should report more detailed results, including those for subtypes of fibre and be stratified by other risk factors to rule out residual confounding. Further assessment of the impact of measurement errors on the risk estimates is also warranted. PMID- 22074853 TI - Promoting successful ageing through integrated care. PMID- 22074854 TI - Fibre and prevention of chronic diseases. PMID- 22074855 TI - Influences of two antibiotic contaminants on the production, release and toxicity of microcystins. AB - The influences of spiramycin and amoxicillin on the algal growth, production and release of target microcystins (MCs), MC-LR, MC-RR and MC-YR, in Microcystis aeruginosa were investigated through the seven-day exposure test. Spiramycin were more toxic to M. aeruginosa than amoxicillin according to their 50 percent effective concentrations (EC(50)) in algal growth, which were 1.15 and 8.03 MUg/l, respectively. At environmentally relevant concentrations of 100 ng/l-1 MUg/l, spiramycin reduced the total MC content per algal cell and inhibited the algal growth, while exposure to amoxicillin led to increases in the total MC content per algal cell and the percentage of extracellular MCs, without affecting the algal growth. Toxicity of MCs in combination with each antibiotic was assessed in the luminescent bacteria test using the toxic unit (TU) approach. The 50 percent effective concentrations for the mixtures (EC(50mix)) were 0.56 TU and 0.48 TU for MCs in combination with spiramycin and amoxicillin, respectively, indicating a synergistic interaction between MCs and each antibiotic (EC(50mix)<1TU). After seven-day exposure to 100 ng/l-1 MUg/l of antibiotics, spiramycin-treated algal media and amoxicillin-treated algal media showed significantly lower (p<0.05) and higher (p<0.05) inhibition on the luminescence of Photobacterium phosphoreum, respectively, compared with the untreated algal medium. These results indicated that the toxicity of MCs were alleviated by spiramycin and enhanced by amoxicillin, and the latter effect would increase threats to the aquatic environment. PMID- 22074856 TI - Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of beta-catenin survival axis. AB - Mounting evidence reveals that selenium possesses chemotherapeutic potential against cancer cells. However, the molecular mechanisms underlying the anti cancer effect of selenium remain elusive. In this study, with the aim to explore the detailed mechanisms how selenite induces apoptosis in colorectal cancer cells, we investigated the role of AKT/beta-catenin signaling, a critical regulator of cell proliferation, survival and tumorigenesis, in selenite-induced apoptosis of colorectal cancer cells and xenograft tumors. We showed that selenite exerted a remarkable inhibitory effect on activation of AKT, leading to suppression of beta-catenin activity and expression of its targets: cyclin D1 and survivin. Further experiments by transient expression of AKT and beta-catenin revealed that inhibition of AKT/beta-catenin was closely correlated with selenite triggered apoptosis. Importantly, MnTMPyP pretreatment implied reactive oxygen species (ROS) was a crucial upstream signal for selenite-triggered inhibition of AKT/beta-catenin. Overall, these observations demonstrate that selenite could induce apoptosis through ROS-dependent inhibition of AKT/beta-catenin signaling in colorectal cancer cells in vitro and in vivo, and our findings yield novel insights into elucidating the mechanisms involved in the anti-cancer effect of selenium. PMID- 22074857 TI - Ostrich--a new avian host of Riemerella columbina. PMID- 22074858 TI - Comparative sequence analysis of poxvirus A32 gene encoded ATPase protein and carboxyl terminal heterogeneity of Indian orf viruses. AB - Thirteen orf virus (ORFV) isolates from natural outbreaks in sheep and goats belonging to different geographical regions of India were analysed on the basis of ORF108 (a homologue of poxviral A32 gene), which is known to encode for ATPase and involved in virion DNA packaging. Comparative sequence analysis of ATPase proteins revealed highly conserved N-terminal region with five different motifs [Walker A, Walker B, A32L specific motifs (III and IV) and a novel AYDG (motif V)] among all poxviruses and divergent carboxyl terminus with either single or double RGD sequences among all Indian ORFV isolates. A homology model and secondary structure predictions of N-terminal region of ORFV A32 revealed that most of the poxviruses including ORFV ATPase protein belong to a distinct clade of the HerA/FtsK super family of DNA packaging proteins. Despite differences in host cell specificity and poxvirus infections among animals, DNA packaging motor domain of poxviruses presumed to share remarkable similarities as indicated by the presence of conserved ATPase motifs in the present investigation. The study also indicated the circulation of heterogeneous strains of ORFV in India and possibilities of differentiation of ORFV strains based on C-terminal heterogeneity. PMID- 22074859 TI - Primary isolation of Mycobacterium bovis from bovine tissues: conditions for maximising the number of positive cultures. AB - In studies of Mycobacterium bovis infection in animals a definitive diagnosis requires the isolation of the organism. However, the optimum conditions for the primary isolation of M. bovis have not been determined. The aim of this study was to determine for primary isolation of M. bovis, (a) the incubation time required to achieve maximum sensitivity (i.e., the number of positive samples identified), (b) the effect of decontaminants on bacterial growth rates, and (c) the influence of media and the number of slopes of media on the number of positive samples detected. Two agar-based media, modified Middlebrook 7H11 (7H11) and tuberculosis blood agar (B83), and an egg-based medium, Stonebrink's (SB) were compared. Three decontaminants, 2% (w/v) sodium hydroxide (NaOH), 0.75% (w/v) and 0.075% (w/v) cetylpyridinium chloride (CPC, also called hexadecylpyridinium chloride, HPC) and 0.5% (w/v) benzalkonium chloride (BC) were evaluated against treatment with sterile distilled water. The inoculated media slopes were incubated for up to 15 weeks. Colonies first appeared after 2 weeks on all media types and 75% of positive slopes were identified by 8 weeks. An incubation time of 15 weeks was required to identify all positive samples. The slowest growth was associated with inocula that contained the fewest viable bacilli. The time to the appearance of colonies was influenced by medium type: the median time to detection of colonies was 28 days on 7H11 and B83, and 36 days on SB. However, SB returned the greatest number of positive samples. Decontamination procedures increased the minimum incubation time required to detect positive cultures, probably due to the toxic effect of the decontaminants. Increasing the number of inoculated slopes resulted in an increased number of positive samples and a decreased time to the detection of colonies. Overall, the detection of M. bovis was significantly influenced by the choice of media, the decontaminant and the duration of incubation of cultures. PMID- 22074861 TI - Floating between the poles of pathology and protection: can we pin down the granuloma in tuberculosis? AB - The granuloma in tuberculosis (TB), referred to as the tubercle, is a lesion containing multiple cell types and is the one definite hallmark of this disease. A number of tubercle phenotypes are seen during infection yet how these contribute to development of TB remains unclear. Here we highlight recent results using diverse models of tubercle development as well as recent findings from studies of human TB in an attempt to illustrate the plasticity of the tubercle and to place it between the poles of pathology and protection. Such insights could lead to future interventions to address TB as a global health issue. PMID- 22074860 TI - Porcine IPEC-J2 intestinal epithelial cells in microbiological investigations. AB - IPEC-J2 cells are porcine intestinal columnar epithelial cells that were isolated from neonatal piglet mid-jejunum. This cell line forms polarized monolayers with high transepithelial electrical resistance when cultured on 0.4 MUm pore-size filters. The cell line is unique in that it is derived from small intestinal tissue (compared to the common human colon-derived lines HT-29, T84, and Caco-2) and is not transformed (compared to the porcine small intestinal line, IPI-2I). Porcine intestinal epithelial cells more closely mimic human physiology than analogous rodent cell lines (e.g. IEC-6 or IEC-18), which is important in studies of zoonotic infections; in addition, they provide specificity to study porcine derived infections. IPEC-J2 cells are increasingly being used in microbiological studies to examine the interactions of various animal and human pathogens, including Salmonella enterica and pathogenic Escherichia coli, with intestinal epithelial cells. The IPEC-J2 cell line has also been employed in some probiotic studies, in which the cells have been used as an initial screening tool for adhesiveness and anti-inflammatory properties of the potential probiotic microorganisms. The validity of these studies is not clear as follow-up studies to assess the efficacy of the probiotics in vivo have not been published to date. The aims of this review are to provide a comprehensive overview of the microbiological studies that have been conducted with IPEC-J2 cells and a reference guide of key cellular and immune markers that have been identified in this cell line that may prove to be useful in future studies. PMID- 22074862 TI - Diversity in the realm of eukaryotic microbe form and function. PMID- 22074863 TI - N-acetyltransferase 2 polymorphisms, tobacco smoking, and breast cancer risk in the breast and prostate cancer cohort consortium. AB - Common polymorphisms in the N-acetyltransferase 2 gene (NAT2) modify the association between cigarette smoking and bladder cancer and have been hypothesized to determine whether active cigarette smoking increases breast cancer risk. The authors sought to replicate the latter hypothesis in a prospective analysis of 6,900 breast cancer cases and 9,903 matched controls drawn from 6 cohorts (1989-2006) in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. Standardized methods were used to genotype the 3 most common polymorphisms that define NAT2 acetylation phenotype (rs1799930, rs1799931, and rs1801280). In unconditional logistic regression analyses, breast cancer risk was higher in women with more than 20 pack-years of active cigarette smoking than in never smokers (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17, 1.39), after controlling for established risk factors other than alcohol consumption and physical inactivity. However, associations were similar for the slow (OR = 1.25, 95% CI: 1.11, 1.39) and rapid/intermediate (OR = 1.24, 95% CI: 1.08, 1.42) acetylation phenotypes, with no evidence of interaction (P = 0.87). These results provide some support for the hypothesis that long-term cigarette smoking may be causally associated with breast cancer risk but underscore the need for caution when interpreting sparse data on gene-environment interactions. PMID- 22074864 TI - Occipital condylar fractures in children: rare or underdiagnosed? AB - A 6-year-old female is described who sustained a fracture of the left occipital condyle after colliding with a car at low speed. The fracture was only visible on thin-slice CT of the neck, which is not routinely recommended in children following a road traffic accident. Fractures of the occipitoantlantoaxial complex are difficult to diagnose by plain radiography, and awareness of this problem needs to be raised among clinicians treating children. PMID- 22074865 TI - The lingual lymph node identified as a sentinel node on CT lymphography in a patient with cN0 squamous cell carcinoma of the tongue. AB - We performed CT lymphography on an 81-year-old female patient with a histologically confirmed squamous cell carcinoma of the tongue with no clinical or radiological evidence of cervical lymph node involvement. The lateral lingual lymph node was identified as a sentinel node, which is the first lymph node to receive drainage from a primary tumour. CT lymphography also showed draining lymphatics passing through the sublingual space, the medial side of the submandibular gland and near the hyoid bone and connected with the middle internal jugular node. Although metastasis to the lateral lingual lymph node is known as one of the crucial events in determining survival outcome in cancer of the tongue and floor of the mouth, very few reports are available on the imaging of the lateral lingual lymph node metastasis. This is the first report regarding the lateral lingual lymph node identified as a sentinel node demonstrated on CT lymphography. PMID- 22074866 TI - Digital subtraction radiography evaluation of longitudinal bone density changes around immediate loading implants: a pilot study. AB - OBJECTIVE: The aim of this study was to assess longitudinal quantitative changes in bone density around different implant loading protocols and implant surfaces measured by digital subtraction radiography (DSR). METHODS: 12 patients received bilateral homologous standard and TiUnite(r) (Nobel Biocare, Kloten, Switzerland) single-tooth implants under 2 implant-loading protocols: immediate loading (8 patients, 16 implants, 12 maxillary) and conventional loading (4 patients, 8 implants, 4 maxillary). Standardized periapical radiographs were taken immediately after implant placement (baseline image) and at the 3-month, 6-month and 12-month follow ups. Radiographic images were digitized and submitted to digital subtraction using the DSR system(r) (Electro Medical System, Nyon, Switzerland), resulting in three subtracted images. Quantitative analysis of bone density was performed using Image Tool(r) software (University of Texas Health Science Centre, San Antonio, TX) to assess pixel value changes in five areas around the implants (crestal, subcrestal, medial third, apical-lateral and apical). RESULTS: Repeated-measures analysis of variance showed that grey levels were significantly influenced by follow-up time and implant-loading protocol. A linear increase in grey levels was found for immediate loading (IML) implants and a significant decrease in grey levels was observed in the 12-month follow up for conventional loading implants. No effect of implant surface treatment was observed. CONCLUSION: In conclusion, IML protocol induced mineral bone gain around single-tooth implants after the first year under function for cases with favourable bone conditions. PMID- 22074867 TI - Imaging findings of neurogenic tumours in the head and neck region. AB - OBJECTIVE: The aim of this study was to describe the CT, MRI and ultrasonography findings of five cases of neurogenic tumours in the head and neck region. METHODS: Five neurogenic tumours were analysed with respect to their CT value, the presence of cystic change, target sign, lobulation, connection to the nerve and vascularity. RESULTS: The contrast-enhanced CT (ECT) of the schwannomas demonstrated either a mass with low enhancement (two out of three cases), which reflected the predominant Antoni B components, or a mass with cystic changes, which was an Antoni A-based schwannoma displaying cystic changes (one out of three cases). On MRI, all tumours showed homogeneous and isointense signals for muscle on T1 weighted images (T1 WIs). T2 weighted images (T2 WIs) and gadolinium (Gd)-enhanced T1 WIs demonstrated target sign in both schwannomas. Ultrasound examination showed a well-defined, ovoid or round hypoechoic mass. The direct connection to the nerve was demonstrated in two of the five cases. Lobulation was observed in only one of the five cases and cystic changes were observed in one of the five cases. In all of the cases, no vascularity was seen in power Doppler images (PDIs) obtained percutaneously. CONCLUSIONS: Low-enhanced areas on ECTs can be specific for schwannomas, which suggests the predominance of Antoni B components. The target sign on T2 WIs and Gd-enhanced T1 WIs can be specific, which can be used to differentiate the two different components (Antoni A and Antoni B). The direct connection to the nerve can be a specific finding for neurogenic tumours; however, at present the sensitivity is 40%. PMID- 22074868 TI - Diagnostic accuracy of proximal enamel subsurface demineralization and its relationship with calcium loss and lesion depth. AB - OBJECTIVE: The aim of this study was to determine the relationship between the amount of calcium loss, lesion depth, and the accuracy of storage phosphor plate (SPP) and film radiographs for the detection of artificial proximal demineralization. METHODS: Standard enamel windows of extracted premolars were exposed to a demineralizing solution for 60 h, 80 h, 100 h and 120 h. Solutions were analysed for calcium concentration by atomic absorption spectrometer and the lesion depths were calculated by a specific formula. All teeth were radiographed with SPPs and F-speed films before and after acid application. Images were evaluated by five observers. Stereomicroscopic and scanning electron microscopic (SEM) observations were carried out to visualize enamel surfaces after acid exposure. Receiver operating characteristic analysis was used for diagnostic accuracy (A(z)). A(z)s were compared with factorial analysis of variance and t tests. The relationship between A(z)s and lesion depths was determined with Pearson's correlation test. RESULTS: Strong positive correlation was found between A(z)s of both radiographic methods and lesion depths. No difference was found between the A(z)s of two radiographic systems for any of the demineralization durations (p > 0.05). Pair-wise comparisons revealed no significant difference in A(z)s of SPPs (p > 0.05), while significant differences were obtained for the A(z)s of films for different demineralization periods (p < 0.05). Stereomicroscopic and SEM observations confirmed demineralizations from superficial to deeper layers of enamel. CONCLUSION: Subsurface enamel demineralization was not accurately detectable with either storage phosphor plates or F-speed films. The amount of calcium loss and the depth of demineralization have a strong relationship with diagnostic accuracy with a significant effect particularly on F-speed films. PMID- 22074869 TI - Radiographic evaluation on prevalence of Stafne bone defect: a study from two centres in Turkey. AB - OBJECTIVES: The aim of this study was to investigate the frequency of Stafne bone defect (SBD) and to describe the clinical and radiological characteristics of detected cases. METHODS: A retrospective study was performed using panoramic radiographs from 34 221 patients undergoing dental treatment in the Department of Oral and Maxillofacial Radiology at Erciyes University and Ataturk University, Turkey. After finding an image compatible with SBD in the radiographs, multislice CT (MSCT) on seven patients and cone beam CT (CBCT) on six patients were performed to confirm the diagnosis. RESULTS: Of the 34 221 patients, 29 (0.08 %) had SBDs, of whom 4 were female (13.8%) and 25 were male (86.2 %). The age range of patients with SBD was 18-77 years (mean age 49.6 years). SBD was found in the lingual molar region in 28 patients and in the lingual canine-premolar region of the mandible in 1 patient. The contour of the concavities on CT images (MSCT and CBCT) was detected. The MSCT revealed glandular tissue within the defects. CONCLUSIONS: According to our results, SBD is an uncommon anomaly. Examination of MSCT images supports the presence of aberrant submandibular glands within these mandibular defects, suggesting that pressure from submandibular gland tissue had caused the SBD, as generally thought. Both CBCT and MSCT can provide adequate support for the detection of SBDs. The CBCT could be suggested as the most suitable non-invasive diagnostic modality for this bony configuration of the mandible since it provides a lower radiation exposure dose than MSCT. PMID- 22074870 TI - Osteosarcoma of the jaws: demographic and CT imaging features. AB - OBJECTIVE: The aim of this study was to evaluate the patient demographic and CT imaging findings of primary osteosarcoma of the jaws. METHODS: 88 primary osteosarcomas of the jaws histopathologically diagnosed during 1997-2007 were reviewed. 21 cases of CT images were reviewed. RESULTS: Of 88 patients, 51 (58%) had tumours in the mandible and 37 (42%) in the maxilla. The mean age was 37.8 years (range 9-80 years). The male-to-female ratio was 1.32:1. The mean age of patients with mandibular lesions was 41.04 years and in those with maxillary lesions it was 33.3 years. CT imaging findings were available in 21 patients. In the maxilla (n = 9), all tumours (100%) arose from the alveolar ridge. In the mandible (n = 12), most tumours (9 cases, 75%), arose from the ramus and/or condyle. All except two lesions had the epicentrum within the medullary cavity of the involved bone. The presence of periosteal reaction was demonstrated in 13 cases (62%). Soft-tissue extension was present in 18 lesions (86%), with calcification identified in 13 (72%). CONCLUSIONS: This study provides age, sex distribution, location and CT imaging features of primary osteosarcoma of the jaws. PMID- 22074871 TI - CT findings of necrotizing sialometaplasia. AB - An otherwise healthy 56-year-old Caucasian female was referred to the radiology department because of an ulceration of her palatal mucosa. Clinically the lesion was suspected to be malignant and a multislice CT examination of the head and neck region was performed. This revealed an ulcer-like cavity with no tumour-like contrast enhancement. No relevant bone changes or suspicious lymph nodes of the neck were detected. Based on the multislice CT findings, necrotizing sialometaplasia was suspected and the diagnosis was verified histopathologically. This report describes the CT findings of necrotizing sialometaplasia at the ulceration stage. PMID- 22074872 TI - Tuberculous osteomyelitis of mandibular condyle: a diagnostic dilemma. AB - The incidence of tuberculosis (TB) is increasing worldwide and so are its consequences. Its oral manifestations are infrequent, occurring in approximately 3% of all cases. Although the primary lesion occurs as a pulmonary infection, the extrapulmonary infections have also shown an increase over the past few years. These infections generally involve the head and neck through haematogenous or lymphatic routes. The clinical presentation may be as an ulcer, granuloma, orofacial TB, TB of the salivary glands or tuberculous lymphadenitis. Rarely, secondary oral manifestations associated with pulmonary infection are seen, which can appear as lesions on the gingiva, palate, lips, tongue, buccal mucosa, frenulum and in the jaw bones. Owing to the rarity of orofacial TB, it seldom arouses clinical suspicion, especially when a positive history of a systemic infection or therapy is denied. Tuberculous involvement of the mandibular condyle is even rarer, and only two such cases are reported so far, both in English language literature. Further, the diagnosis of such a case is extremely difficult as there are no specific signs pathogonomic of infection. The only manifestation may be a localized painful swelling of the jaw. The presented case is of osteomyelitis of the mandibular condyle in a 20-year-old male patient in whom TB was later suspected. In this case report the role of diagnostic techniques is emphasized as the osteomyelitis of the condyle has the risk of being easily missed owing to its atypical signs and symptoms and atypical radiographic appearance. PMID- 22074873 TI - Radiological examination of the articular eminence morphology using cone beam CT. AB - OBJECTIVE: The purpose of the present study was to investigate the articular eminence inclination and height according to age and gender in patients with temporomandibular joint (TMJ) dysfunction and healthy controls using cone beam CT (CBCT). METHODS: The measurements were performed on CBCT records of 52 TMJ dysfunction patients (11 males and 41 females) and 41 control patients (17 males and 24 females). The eminence inclination and height were measured on the CBCT images. RESULTS: The eminence inclination and height values were higher in males than in females in both TMJ dysfunction patient and control groups; however, these differences were not statistically significant (p>0.05). While no statistically significant differences were found in the eminence inclination and height values between the age groups (p>0.05) in the TMJ dysfunction patient group, there were statistically significant differences in the control group. The eminence inclination was highest between the ages of 21 and 30 years and showed a decrease after the age of 30 years. Additionally, the eminence inclinations of the control patients were statistically higher than those of the TMJ dysfunction patients. CONCLUSION: There were no statistically significant differences in eminence inclination and height according to gender. The eminence inclination reaches its highest value between the ages of 21 and 30 years and shows a decrease after the age of 31 years in healthy patients. The eminence inclination was steeper in healthy control patients than in patients with TMJ dysfunction. PMID- 22074874 TI - CT findings in two cases of lobular capillary haemangioma of the nasal cavity: focusing on the enhancement pattern. AB - Lobular capillary haemangioma, known as pyogenic granuloma, is a relatively common benign vascular neoplasm that is composed of hyperplastic clusters of capillaries arranged in a lobular architectural pattern. Most mucosal lobular capillary haemangioma (LCH) of the head and neck arise in the oral cavity, but the nasal cavity involvement is rare. We report here on the CT imaging findings of two cases of LCH involving the nasal cavity, with an emphasis being placed on the different pattern of enhancement of the tumour on the enhanced CT scans. PMID- 22074875 TI - Multiple nodular fasciitis in the mandibular border area which is misdiagnosed as metastatic lymph node. AB - Nodular fasciitis (NF) is a benign lesion that has proliferative fibroblasts and myofibroblasts. NF is similar to a tumour and has infiltrative properties. We describe a rare case of multiple nodular fasciitis occurring in the mandibular border area of a 51-year-old male. Radiological and histological features are discussed along with a brief review of the literature. In addition, the importance of a differential diagnosis for this lesion is also discussed. PMID- 22074876 TI - A multilocular radiolucency with spindle cell proliferation in a case of ossifying fibroma: a potential pitfall. AB - Ossifying fibroma (OF) is a benign tumour characterized by cementum or bone formation accompanied by a fibrocellular stroma. The diagnosis of OF may be apparent when the histological features are supported by clinical and radiological information. In this report, an OF with predominantly spindle cell proliferation and purely radiolucent, multilocular lesion in a middle-aged woman is presented. PMID- 22074877 TI - The importance of cone beam CT in the radiological detection of osteomalacia. AB - Although osteomalacia is one of the most common osteometabolic diseases among the elderly, there is no case in the literature that presents the effects of osteomalacia in detail using cone beam CT (CBCT). While thin and porous bones are the most common radiographic sign of the disease, the radiological hallmarks are pseudofractures (Looser's zone). We coincidentally detected osteomalacia in a 23 year-old female and we showed the pseudofracture on CBCT images. In the present case, we aim to present the images of osteomalacia that were detected by CBCT in detail. CBCT has an important value in screening for osteomalacia. PMID- 22074878 TI - Pre-operative diagnostic radiograph interpretation by general dental practitioners for root canal treatment. AB - OBJECTIVES: The aim of this study was to evaluate which radicular radiographic features general dentists want to interpret, determine which of the radicular radiographic features general dentists interpret and which ones they miss in a diagnostic radiograph and correlate how accurately general dentists are able to interpret radiographic features. METHODS: 20 general dental practitioners were selected and given 2 sets of questionnaires. The first set asked them to fill out the findings they would elucidate in a diagnostic radiograph while the second set consisted of 30 randomly selected intraoral radiographs to interpret. RESULTS: In the first set of questionnaires, more than 50% of dentists said they would interpret periapical changes, calcification, root curvature and the number of root canals. Less than 50% said they would interpret canal morphology, open apex, resorption, fracture, number of roots and lamina dura. In the second set of questionnaires, more than 90% missed grade 1 or 2 periapical changes (according to periapical index scoring), resorption and canal calcification. More than 80% of dentists missed extra roots and root curvature buccally while no dentists were able to interpret the periodontal ligament width changes, lamina dura and canal variation (C-shape). Using a paired t-test, there was significant variation in answers between the first set and second set of questionnaires. CONCLUSION: It is concluded from this study that general dental practitioners are able to detect radiographic changes when they are extensive but they miss periodontal ligament width and lamina dura changes. PMID- 22074879 TI - [West Nile fever/encephalitis: re-emergence in Europe and the situation in Spain]. AB - Some arbovirosis have increased their incidence and geographic range in the past few years. This phenomenon has been particularly noticeable in the case of West Nile fever/encephalitis. This disease did not receive much attention until serious outbreaks occurred in Romania, Russia and Israel between 1996 and 1999. But the event drawing an unprecedented attention to this disease was its occurrence in New York in 1999. Since then its incidence and geographic range has not ceased to grow. In America it has extended from coast to coast and from Canada to Argentina. In Europe, the disease incidence has increased in areas where it had already been reported, and, recently, affected other areas where it had never been observed before. The present article is a review on the virus, the disease, and its situation in Europe, with special reference to Spain, where in 2010 human and veterinary cases were reported. PMID- 22074880 TI - Diverse rare lipid-related metabolites including omega-7 and omega-9 alkenylitaconic acids (ceriporic acids) secreted by a selective white rot fungus, Ceriporiopsis subvermispora. AB - Ceriporiopsis subvermispora is a selective white-rot fungus that secretes alk(en)ylitaconic acids named ceriporic acids, known as ion redox silencers. In this study, we analysed a series of extracellular lipid-related metabolites produced by the fungus and found that a wide variety of ceriporic acids and fatty acids, including those with odd-numbered and very long-chains, were produced in wood meal cultures. Two new ceriporic acids, (R)-3-[(Z)-tetradec-7-enyl]-itaconic acid (ceriporic acid E) and (R)-3-[(Z)-tetradec-5-enyl]-itaconic acid (ceriporic acid F), were for the first time identified by dimethyl disulfide derivatisation, followed by GC/EI-MS, (1)H and homonuclear J-resolved 2D NMR and feeding experiments with [(13)C-U] glucose coupled with multiple-stage mass spectrometry. In separation by GC and LC, a reversed correlation of elution sequences between a nonpolar GC column and an ODS-LC column for cis and trans isomers of omega7 and omega9 lipids was found, and the elution of new metabolites was in accordance with the prevailing theory. The biosynthetic precursors of ceriporic acid F can be proposed as oxaloacetate and 16:1Delta7-CoA. Because fatty acids biosynthesised from 16:1Delta7-CoA have been reported for only a limited number of organisms, the highly individual structure of ceriporic acid F is highlighted. PMID- 22074882 TI - Spectroscopic (FT-IR, FT-Raman and UV-vis) investigation and frontier molecular orbitals analysis on 3-methyl-2-nitrophenol using hybrid computational calculations. AB - In the present study, the FT-IR and FT-Raman spectra of 3-methyl-2-nitrophenol (C(7)H(7)O(3)N) (3M2NP) have been recorded in the range of 4000-100 cm(-1). The fundamental modes of vibrational frequencies of 3M2NP are assigned. All the geometrical parameters have been calculated by HF and DFT (LSDA and B3LYP) methods with 6-31G(d,p) and 6-311G(d,p) basis sets. Optimized geometries of the molecule have been interpreted and compared with the reported experimental values for phenol and some substituted phenol. The harmonic and anharmonic vibrational wave numbers, IR intensities and Raman activities are calculated at the same theory levels used in geometry optimization. The calculated frequencies are scaled and compared with experimental values. The scaled vibrational frequencies at LSDA/B3LYP/6-311G(d,p) seem to coincide with the experimentally observed values with acceptable deviations. The impact of substitutions on the benzene structure is investigated. The molecular interactions between the substitutions (OH, CH(3) and NO(2)) are also analyzed. A detailed interpretation of the infrared spectra of was also reported more precisely. Charge transfer occurring in the molecule between HOMO and LUMO energies, frontier energy gap are calculated and presented. On the basis of the thermodynamic properties of the title compound at different temperatures have been calculated, revealing the correlations between standard heat capacities (C) standard entropies (S), and standard enthalpy changes (H) and temperatures. PMID- 22074881 TI - Distribution of c-Fos immunoreactivity in the rat brain following abuse-like toluene vapor inhalation. AB - Inhalation of vapors from toluene-containing products results in euphoria accompanied by a variety of cognitive impairments and motor dysfunctions. The profound behavioral changes observed during and following toluene inhalation suggest changes in the activity of cells in potentially many brain regions; however, a comprehensive assessment of the neuroanatomical structures activated by toluene vapor has not been completed. Thus in the present study we systematically mapped in over 140 brain structures the distribution of c-Fos immunoreactivity (c-Fos IR), a proxy for neural activation, following exposure to an abuse-like concentration (~5000 ppm) of toluene vapor for 0, 5, 10 or 30 min. Quantitative analyses revealed increases in c-Fos IR in about one-third of the brain structures examined, with most of these structures significantly activated only after prolonged toluene exposure. The majority of brain structures activated by toluene were found in the forebrain and midbrain, with particularly pronounced activation in nuclei implicated in the processing of rewarding, emotional, and olfactory stimuli, and those controlling motor output. These structures included the ventral tegmental area, nucleus accumbens, select regions of the amygdala and hypothalamus, cingulate cortex, olfactory nuclei, piriform cortex, secondary motor cortex and caudate-putamen. In contrast, all subregions of the hippocampus and most thalamic nuclei were not significantly activated by toluene vapor. In the brainstem, effects of toluene vapor were restricted to select nuclei in the pons. The pattern of c-Fos IR evoked by inhalation of toluene vapor appears distinct from other psychoactive substances, consistent with the unique and complex behavioral outcomes associated with acute toluene inhalation. PMID- 22074883 TI - Molecular structure and properties of wool fiber surface-grafted with nano antibacterial materials. AB - Wool fiber was modified by ultraviolet irradiation (UV) and functionalized by grafting antibacterial agent. The structure and properties of antibacterial wool fiber were discussed in detail. The secondary structure changes and crystal structure were analyzed based on Fourier Transformation Raman Spectrometry (FTR) and X-ray diffraction (XRD). The results show that the disordered degree of UV treated sample was increased and the antibacterial sample became more oriented. Compared with parent wool fiber, the antibacterial wool fiber was improved in mechanical property. The force, tensile strength and elongation were increased by 18%, 16%, and 7%, respectively. Also, the anti-shrinkage performance was increased because of the decrease in the directional frictional effect (DFE). PMID- 22074884 TI - The function of prehistoric lithic tools: a combined study of use-wear analysis and FTIR microspectroscopy. AB - The application of combined use-wear analysis and FTIR micro spectroscopy for the investigation of the flint and obsidian tools from the archaeological sites of Masseria Candelaro (Foggia, Italy) and Sant'Anna di Oria (Brindisi, Italy) aiming to clarify their functional use is described. The tools excavated in the former site showed in a very high percentage spectroscopically detectable residues on their working edges. The identification of micro deposits is based on comparison with a great number of replicas studied in the same experimental conditions. FTIR data confirmed in almost all cases the use-wear analysis suggestions and added details about the material processed and about the working procedures. PMID- 22074885 TI - Synthesis, X-ray crystal structure and optical properties of novel 5-(3-aryl-1H pyrazol-5-yl)-2-(6-methoxy-3-methylbenzofuran-2-yl)-1,3,4-oxadiazole. AB - A series of novel 5-(3-aryl-1H-pyrazol-5-yl)-2-(6-methoxy-3-methylbenzofuran-2 yl)-1,3,4-oxadiazole derivatives has been synthesized from 6-methoxy-3 methylbenzofuran-2-carboxylic acid and ethyl 3-aryl-1H-pyrazole-5-carboxylate. The structures of compounds obtained were determined by IR, (1)H NMR and HRMS spectra. Typically, the spatial structure of compound 7e was determined by using X-ray diffraction analysis. UV-vis absorption and fluorescence spectral characteristics of the compounds in dichloromethane and acetonitrile were investigated. The results showed that the absorption maxima of the compounds vary from 321 to 339 nm depending on the substituents in N-1 position of pyrazole moiety and para position of benzene moiety. The maximum emission spectra of compounds in two different solvents were mainly dependent on groups in N-1 position of pyrazole moiety. The intensity of absorption and fluorescence was also correlated with substituents on the aryl ring bonded to pyrazole moiety. In addition, the absorption and emission spectra of these compounds change with increasing solvent polarity. PMID- 22074886 TI - Raman spectroscopy of selected tsumcorite Pb(Zn,Fe3+)2(AsO4)2(OH,H2O) minerals- implications for arsenate accumulation. AB - The presence of arsenic in the environment is a hazard. The accumulation of arsenate by a range of cations in the formation of minerals provides a mechanism for the accumulation of arsenate. The formation of the tsumcorite minerals is an example of a series of minerals which accumulate arsenate. There are about twelve examples in this mineral group. Raman spectroscopy offers a method for the analysis of these minerals. The structure of selected tsumcorite minerals with arsenate and sulphate anions were analysed by Raman spectroscopy. Isomorphic substitution of sulphate for arsenate is observed for gartrellite and thometzekite. A comparison is made with the sulphate bearing mineral natrochalcite. The position of the hydroxyl and water stretching vibrations are related to the strength of the hydrogen bond formed between the OH unit and the AsO(4)(3-) anion. Characteristic Raman spectra of the minerals enable the assignment of the bands to specific vibrational modes. PMID- 22074887 TI - Vibrational spectroscopic, first-order hyperpolarizability and HOMO, LUMO studies of 4-chloro-2-(trifluoromethyl) aniline based on DFT calculations. AB - The Fourier-transform infrared and FT-Raman spectra of 4-chloro-2 (trifluoromethyl) aniline (4C2TFA) were recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1) respectively. Quantum chemical calculations of energies, geometrical structure and vibrational wavenumbers of 4C2TFA were carried out by density functional theory (DFT/B3LYP) method with 6-311+G(d,p) and 6-311++G(d,p) basis sets. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. The values of the total dipole moment (MU) and the first order hyperpolarizability (beta) of the investigated compound were computed using B3LYP/6-311++G(d,p) calculations. The calculated results also show that 4C2TFA might have microscopic non-linear optical (NLO) behavior with non-zero values. A detailed interpretation of infrared and Raman spectra of 4C2TFA is also reported. The calculated HOMO-LUMO energy gap shows that charge transfer occurs within the molecule. PMID- 22074888 TI - Spectroscopic studies on the intermolecular charge transfer interaction of Fe(II) and Fe(III)-phthalocyanines with 2,3,5,6-tetrachloro-1,4-benzoquinone and its application in colorimetric sensing of amino acids and amines. AB - The interactions of Fe(II)Pc and Fe(III)Pc with pi-acceptor 2,3,5,6-tetrachloro 1,4-benzoquinone (p-chloranil, p-CHL) have been investigated spectroscopically (UV/vis and FT-IR) and spectrofluorimetrically at three different temperatures. The stoichiometry of the complexes was found to be 1:1. The results of electronic spectral studies indicated that the formation constant for Fe(II)Pc-p-CHL system is found to be higher than that for Fe(III)Pc-p-CHL system. This observation is well supported by the results of fluorescence quenching studies and the association constants calculated for Fe(II)Pc-p-CHL system is 4.2 * 10(3) mol L( 1) and that for Fe(III)Pc-p-CHL system is 2.2 * 10(3) mol L(-1). The data are discussed in terms of physico-chemical parameters viz. molar extinction coefficient, oscillator strength, dipole moment, ionization potential, dissociation energy and thermodynamic parameters. The results indicated that the formation of pi-pi CT complex is spontaneous and endothermic. Preliminary studies indicated that the CT complex can effectively be used as a colorimetric agent for sensing amino acids and amines. PMID- 22074889 TI - Analysis of vibrational spectra and nonlinear optical properties of organic molecule L-alaninium formate. AB - Vibrational and electronic spectra of the crystallized nonlinear optical molecule L-alaninium formate have been recorded and analyzed. The equilibrium geometry, vibrational wavenumbers, and the first order hyperpolarizability of the crystal have been calculated with the help of density functional theory computations. The N-H...O bond distance shows the presence of intramolecular hydrogen bonding and the result is confirmed by the natural bond orbital analysis. The HOMO-LUMO energy gap and the first order hyperpolarizability was calculated and it supports the nonlinear optical activity of the L-alaninium formate crystal. PMID- 22074890 TI - Growth, spectroscopic, dielectric and nonlinear optical studies of semi organic nonlinear optical crystal--L-alanine lithium chloride. AB - A new and efficient semi organic nonlinear optical crystal (NLO) from the amino acid family L-alanine lithium chloride (LAL) has been grown by slow evaporation technique from aqueous solution. The functional groups were identified from NMR spectral studies. Mass spectral analysis shows the molecular ion mass. Dielectric studies has been done for the grown crystal and relative SHG efficiency is measured by Kurtz and Perry method and found to about 0.43 times that of standard potassium dihydrogen phosphate (KDP) crystals. The compound crystallized in non centrosymmetric space group Pna21. The results have been discussed in detail. PMID- 22074891 TI - Predicting the risk of cardiovascular disease in people exposed to moderate to high levels of dioxin. AB - Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Dioxins can cause cardiovascular toxicity in experimental animals. The potential role of dioxin exposure as a preventable risk factor has attracted the attention of public health services, especially because dioxin exposure is a ubiquitous problem. We aimed to investigate and clarify the effect on CVD risk of moderate-to-high exposure to dioxins. This cross-sectional study investigated 914 residents without CVD near a deserted pentachlorophenol factory. CVD-related factors were measured to examine their associations with serum dioxin. We also investigated associations between serum dioxins and the Framingham risk score. Serum PCDD/F levels were significantly positively associated with CVD risk in both genders (Men: b=0.023, P<0.001; Women: b=0.005, P<0.001; All: b=0.013, P<0.001). After adjusting for confounding factors, participants with higher serum PCDD/F levels had a higher risk for CVD than did the reference group (serum PCDD/levels<9.8 pg WHO(98)-TEQ(DF)/g lipid) (25th to <50th percentile, adjusted odds ratio (AOR)=2.96 [95% confidence interval (CI)=1.13-7.75]; 50th to<75th percentile, AOR=3.37 [1.32-8.59]; >=75th percentile, AOR=6.22 [2.47-15.63]). We hypothesize that accumulated dioxins heightens the cardiovascular risk. PMID- 22074892 TI - Mechanochemical destruction of pentachloronitrobenzene with reactive iron powder. AB - Pentachloronitrobenzene (PCNB) has been identified as a potential persistent organic pollutant, and received concerns from many countries for regulation due to its impurities such as dioxins and furans. Considering the need for its disposal, the mechanochemical destruction approach was investigated for the applicability. PCNB was co-ground with reactive iron powder in a high energy planetary ball mill at room temperature. PCNB was found to be destructed finally, and the Dioxins and coplanar-PCBs concentrations in PCNB had been degraded from 1146 ng-TEQ/kg to 0.04 ng-TEQ/kg finally. Pentachloroaniline (PCA), 2,3,5,6 tetrachloroaniline (2,3,5,6-TeCBA) and 3,4,5,6-tetrachloroaniline (3,4,5,6-TeCBA) were detected as intermediates during the ball milling process and were destructed completely after 8h milling. The amount of water soluble chlorides (Cl(-)) reached 95.8% of the theoretical amount of chlorine in original PCNB sample after 12h ball milling. The solvent acetone might play a role as the main hydrogen donor, which gives rise to the amination reaction of nitro-group. Metastable structures with high molecular were proposed to be formed during the ball milling process as intermediates. Carbonization was confirmed by Raman spectrum as the final degradation product of PCNB. PMID- 22074893 TI - Growth and cesium uptake responses of Phytolacca americana Linn. and Amaranthus cruentus L. grown on cesium contaminated soil to elevated CO2 or inoculation with a plant growth promoting rhizobacterium Burkholderia sp. D54, or in combination. AB - Growth and cesium uptake responses of plants to elevated CO(2) and microbial inoculation, alone or in combination, can be explored for clean-up of contaminated soils, and this induced phytoextraction may be better than the natural process. The present study used open-top chambers to investigate combined effects of Burkholderia sp. D54 inoculation and elevated CO(2) (860 MUL L(-1)) on growth and Cs uptake by Phytolacca americana and Amaranthus cruentus grown on soil spiked with various levels of Cs (0-1000 mg kg(-1)). Elevated CO(2) and bacterial inoculation, alone or in combination, significantly increased biomass production with increased magnitude, ranging from 22% to 139% for P. americana, and 14% to 254% for A. cruentus. Total tissue Cs in both plants was significantly greater for bacterial inoculation treatment singly, and combined treatments of bacterial inoculation and elevated CO(2) than for the control treatment in most cases. Regardless of CO(2) concentrations and bacterial inoculation, A. cruentus had higher tissue Cs concentration, Cs transfer factors and concentration ratios than P. americana, but they had slightly different contents of antioxidant enzymes. It is concluded that combined effects of elevated CO(2) and microbial inoculation with regard to plant ability to grow and remove radionuclides from soil can be explored for CO(2)- and microbe-assisted phytoextraction technology. PMID- 22074895 TI - When more is less: failure to compress discourse with re-telling in normal ageing. AB - When young adults tell the same story repeatedly, their narratives become progressively more concise. Although impaired discourse production has been reliably demonstrated in the elderly, changes in narrative production with repetition have not been investigated in this cohort. Thirty young (aged 18-49 years, M=28.77, SD=9.73) and thirty elderly (aged 65+ years, M=73.57, SD=6.80) adults completed a discourse production task involving narrative construction using an eight-frame cartoon. Narratives were repeated 4 consecutive times. Variables analysed were narrative duration, word count and fluency (words/sec). For all variables the compression index for the elderly group was significantly lower than that for young participants. Further, compared to their younger counterparts, elderly adults were less able to improve the cohesion of their narratives with repetition. These findings suggest that the elderly have a reduced capacity to generate and refine discourse representations. PMID- 22074894 TI - Degradation pathway of pentachlorophenol by Mucor plumbeus involves phase II conjugation and oxidation-reduction reactions. AB - Environmental pollution by pentachlorophenol (PCP) is a critical concern worldwide and fungal bioremediation constitutes an elegant and environment friendly solution. Mucorales from the Zygomycota phylum are often observed to be competitive in field conditions and Mucor plumbeus, in particular, can efficiently deplete PCP from media. The pathway for PCP degradation used by this fungus has not been investigated. In this study, PCP-derived metabolites were identified by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, including tetra- and tri-chlorohydroquinones and phase II conjugated metabolites. Amongst the latter are the previously reported glucose, sulfate and ribose conjugates, and identified for the first time in fungi sulfate glucose conjugates. A PCP transformation pathway for M. plumbeus is proposed, which excludes the involvement of cytochrome P-450 and extracellular ligninolytic enzymes. PMID- 22074896 TI - The distribution of small preantral follicles within the ovaries of prepubertal African elephants (Loxodonta africana). AB - BACKGROUND: Data on the distribution of primordial (single layer of squamous granulosa cells), early primary (some granulosa cells cuboidal) and primary (all granulosa cells cuboidal) follicles, grouped together as small follicles (SF) within the ovary of the elephant is lacking, yet such information is necessary to be able to estimate accurately the total numbers of small follicles in the ovaries of elephant throughout their lifespan. AIM: To determine if the density of SF differs between ovaries, between the surfaces of an ovary, or between the interpolar and intermarginal zones of an ovary. MATERIALS/METHODS: Stereological techniques were employed on 25MUm thick histological sections of the ovaries recovered from 12 prepubertal elephant calves aged 2 months to 4.5 years. Cell densities were calculated using the optical brick method and Cavalieri's principle for volume calculation. RESULTS: The density of SF (numbers of SF per unbiased counting frame [UCF]) did not differ between the left (1.11+/-0.39 (mean+/-sd)) and right (1.10+/-0.39) ovaries (P=0.82, n=12), or between the lateral (median 1.24; interquartile range 0.85-1.39) and medial (1.03; 0.76-1.36) surfaces of the ovary (P=0.22, n=24) or among the 5 segments of the ovary between the two poles (P=0.20, n=24). The third of the cortex nearest to the mesovarial margin of the ovary had fewer small follicles per UCF (0.85; 0.51-1.28) than the middle third (1.01; 0.78-1.42; P=0.034), and the third adjacent to the free margin (1.27; 0.79-1.51; P=0.0024), n=24 per group. CONCLUSION: Providing a random sample is taken from the full interpolar and intermarginal dimensions of ovary of a non-pregnant elephant, the density of small follicles throughout the cortex may be accurately measured using stereological techniques applied to one of its surfaces. PMID- 22074897 TI - The calcium signal: a universal carrier to code, decode and transduce information. PMID- 22074898 TI - The neural coding of expected and unexpected monetary performance outcomes: dissociations between active and observational learning. AB - Successful adaptation to the environment requires the learning of stimulus response-outcome associations. Such associations can be learned actively by trial and error or by observing the behaviour and accompanying outcomes in other persons. The present study investigated similarities and differences in the neural mechanisms of active and observational learning from monetary feedback using functional magnetic resonance imaging. Two groups of 15 subjects each - active and observational learners - participated in the experiment. On every trial, active learners chose between two stimuli and received monetary feedback. Each observational learner observed the choices and outcomes of one active learner. Learning performance as assessed via active test trials without feedback was comparable between groups. Different activation patterns were observed for the processing of unexpected vs. expected monetary feedback in active and observational learners, particularly for positive outcomes. Activity for unexpected vs. expected reward was stronger in the right striatum in active learning, while activity in the hippocampus was bilaterally enhanced in observational and reduced in active learning. Modulation of activity by prediction error (PE) magnitude was observed in the right putamen in both types of learning, whereas PE related activations in the right anterior caudate nucleus and in the medial orbitofrontal cortex were stronger for active learning. The striatum and orbitofrontal cortex thus appear to link reward stimuli to own behavioural reactions and are less strongly involved when the behavioural outcome refers to another person's action. Alternative explanations such as differences in reward value between active and observational learning are also discussed. PMID- 22074899 TI - The role of endogenous dynorphin in ethanol-induced state-dependent CPP. AB - The aim of this study was to determine the role of the endogenous dynorphin/kappa opioid receptor (DYN/KOP) system in ethanol-induced state-dependent conditioned place preference (CPP). To this end, mice lacking the pro-DYN gene and their wild type littermates/controls were tested for baseline place preference on day 1, received 15-min morning and afternoon conditionings with saline or ethanol (2g/kg) each day for three consecutive days and were then tested for CPP under a drug-free state on day 5 and following a saline or ethanol (1 or 2g/kg) challenge on day 8. Given that compensatory developmental changes may occur in knockout mice, the effect of nor-binaltorphimine (nor-BNI), a KOP antagonist, on state dependent CPP induced by ethanol was also studied in wild-type mice. On day 1, mice were tested for baseline place preference and, 4h later, treated with saline or nor-BNI (10mg/kg). On days 2-4, mice received 15-min morning and afternoon conditionings and were tested for CPP under a drug-free state on day 5 and following an ethanol (1g/kg) challenge on day 8. A comparable CPP was observed in mice lacking the pro-DYN gene and their wild-type littermates/controls as well as in wild-type mice treated with nor-BNI and their saline-treated controls. However, these mice compared to their respective controls exhibited a greater CPP response following an ethanol (1g/kg) challenge, suggesting that the endogenous DYN/KOP system may negatively regulate ethanol-induced state-dependent CPP. PMID- 22074900 TI - Effects of apomorphine and beta-carbolines on firing rate of neurons in the ventral pallidum in the rats. AB - The ventral pallidum (VP) is a critical element of the mesocorticolimbic system that is inter-connected with motor and limbic structures and may be considered as an interface between motivational and effector neural signals. Dopamine is important in behavioral output of the VP, and dysfunctioning its dopamine quantity leads to various neuropsychiatric disorders. Understanding neural substrate underlying this phenomenon has become an important affair in recent years. In this study, neuronal activities were recorded from the VP in presence or absence of the mixed dopamine D1/D2 receptor agonist, apomorphine, and/or beta carbolines, using an extracellular single-unit recording technique. We reported that subcutaneous administration of apomorphine (0.5mg/kg) decreased neural activity in the VP. In addition, neither harmine (7.8 mg/kg; i.p.) nor harmane (4 mg/kg; i.p.) and norharmane (2.5mg/kg; i.p.) had any effect on neural firing in the VP. Finally, pretreatment with beta-carbolines prevented the apomorphine induced inhibition on VP firing rate. Thus, according to the results of aforementioned study and our results in the present study, we can conclude that presumably most responses in the VP are D2 dopamine dependent. Although the beta carbolines were unable to alter neural activity in the VP, interestingly, pretreatment with beta-carbolines protect decreasing in firing rate of neurons in the VP followed by apomorphine administration. This protective effect could be explained by interaction between beta-carbolines and dopaminergic mechanisms. PMID- 22074901 TI - Anaerobic digestion of extruded OFMSW. AB - Organic fraction of municipal solid waste (OFMSW) was used to feed two pilot plants of 1000 l working in anaerobic conditions. The OFMSW had previously been treated using a system of extrusion which, due to exerted pressure, separates the undesired fractions of waste from organic waste and reduces the organic fraction in a kind of homogeneous jam. Pilot tests were performed in semi-continuous conditions with a stepwise progressive increase of the total solids content (TS) of the input material from 3% TS w/w (1.5 g VS l(-1) d(-1) organic loading rate) to 10% TS w/w (4.3 g VS l(-1) d(-1) organic loading rate) using activated sludge as diluting agent. The average specific biogas production obtained was 600 l kg( 1)VS. When the input TS content was increased to 10% w/w, the biogas average specific production went up to 800 l kg(-1)VS. The methane content in the biogas was always higher than 60% measured by volume. PMID- 22074902 TI - A novel 2,3-xylenol-utilizing Pseudomonas isolate capable of degrading multiple phenolic compounds. AB - This work characterized a novel 2,3-xylenol-utilizing Pseudomonas isolate XQ23. From 16S rRNA phylogenetic analysis, XQ23 was found to be a member of the Pseudomonas putida group. Most of its physiological characteristics also shared similarities to P. putida. Phenols were catabolized by the meta-cleavage pathway. The dependence of the specific growth rate on 2,3-xylenol concentration could be well fitted by the Haldane model, with the maximum occurring at the concentration around 180 mg l(-1). Kinetic parameters indicated that XQ23 was sensitive to 2,3 xylenol and had low affinity. Three patterns, i.e. constant, linear decline, and allometric decline, were proposed to describe the biomass yields of phenols during bacterial degradation and XQ23 under 2,3-xylenol culturing conditions followed the allometric pattern. In a mineral-salts medium supplemented with 180 mg l(-1) of 2,3-xylenol as the sole carbon and energy source, over 40% of 2,3 xylenol was turned into CO(2) to provide energy by complete oxidization. PMID- 22074903 TI - Technoeconomic assessment of phenanthrene degradation by Pseudomonas stutzeri CECT 930 in a batch bioreactor. AB - Polycyclic aromatic hydrocarbons (PAHs) are among the most persistent pollutants that accumulate in natural environment mainly as a result of anthropogenic activities. Therefore, the improvement of the available bank of microbial resources and information is crucial to the proper management of PAHs-polluted sites and effluents. In this work, Pseudomonas stutzeri CECT 930 was selected for aerobically degrading an aqueous effluent containing phenanthrene (PHE). Maximum PHE degradation of 90% was obtained both at flask and stirred tank bioreactor scale. All the experimental data were fitted to logistic and Luedeking and Piret models, and licensed to quantitatively ascertain a stronger dependence on the biomass of the metabolites triggering the bioremediation process. In addition, PHE degradation via protocatechuate pathway was elucidated through GC-MS data. Finally, based on the promising results of biodegradation, a preliminary economic evaluation of this process at industrial scale was approached by means of simulation data obtained with SuperPro Designer. PMID- 22074904 TI - Valuable chemicals by the enzymatic modification of molecules of natural origin: terpenoids, steroids, phenolics and related compounds. AB - A renewed interest for using natural organic molecules for the production of valuable chemicals is observed in current organic processes. Natural compounds provide the access to natural grade chemicals when submitted to physical treatments or biotechnological processes. Dealing with structurally complex molecules, they can provide complex core structures for hemisynthesis purposes, and in many instances they offer the advantage of providing sustainable processes when using renewable resources. These assets could be synergistic with the assets of biocatalytic processes, to end-up with efficient and sustainable processes in the organic synthesis of valuable products. In this review, we have gathered a selection of examples on the use of enzymes for the modification of molecules of natural origin being either purified compounds (terpenoids, steroids, phenolics) or mixtures (essential oils, natural extracts) to access fine chemicals or organic polymers. PMID- 22074905 TI - Effect of carbon source, C/N ratio, nitrate and dissolved oxygen concentration on nitrite and ammonium production from denitrification process by Pseudomonas stutzeri D6. AB - Pseudomonas stutzeri D6, selectively isolated from activated sludge was used to study NO(2)(-) and NH(4)(+) production from denitrification processes. Changes in carbon type, C/N ratio and oxygen concentration significantly influenced the magnitude of NO(2)(-) and NH(4)(+) accumulation through denitrification. D6 showed a preference for citrate and acetate, which led to the largest quantity of nitrate reduced and which were exhausted most rapidly, with minimal intermediate products accumulation. It is found that at higher initial organic carbon concentration or for directly metabolic carbon type more complete denitrification could be obtained as a result of increase of the oxygen consumption rate by substrate stimulation. The higher the oxygen concentration in the culture was, the higher the intermediate products concentration became. The experiment showed that NO(2)(-) and NH(4)(+) production was only slightly influenced by nitrate concentration. Biological nitrogen removal systems should be optimized to promote complete denitrification to minimize NO(2)(-) and NH(4)(+) accumulation. PMID- 22074906 TI - Fermentative production of ethanol from syngas using novel moderately alkaliphilic strains of Alkalibaculum bacchi. AB - Ethanol production from syngas using three moderately alkaliphilic strains of a novel genus and species Alkalibaculum bacchi CP11(T), CP13 and CP15 was investigated in 250 ml bottle fermentations containing 100ml of yeast extract medium at 37 degrees C and pH 8.0. Two commercial syngas mixtures (Syngas I: 20% CO, 15% CO(2), 5% H(2), 60% N(2)) and (Syngas II: 40% CO, 30% CO(2), 30% H(2)) were used. Syngas I and Syngas II represent gasified biomass and coal, respectively. The maximum ethanol concentration (1.7 g l(-1)) and yield from CO (76%) were obtained with strain CP15 and Syngas II after 360 h. CP15 produced over twofold more ethanol with Syngas I compared to strains CP11(T) and CP13. In addition, CP15 produced 18% and 71% more ethanol using Syngas II compared to strains CP11(T) and CP13, respectively. These results show that CP15 is the most promising for ethanol production because of its higher growth and ethanol production rates and yield compared to CP11(T) and CP13. PMID- 22074907 TI - Mesophilic and thermophilic anaerobic co-digestion of rendering plant and slaughterhouse wastes. AB - Co-digestion of rendering and slaughterhouse wastes was studied in laboratory scale semi-continuously fed continuously stirred tank reactors (CSTRs) at 35 and 55 degrees C. All in all, 10 different rendering plant and slaughterhouse waste fractions were characterised showing high contents of lipids and proteins, and methane potentials of 262-572 dm(3)CH(4)/kg volatile solids(VS)(added). In mesophilic CSTR methane yields of ca 720 dm(3) CH(4)/kg VS(fed) were obtained with organic loading rates (OLR) of 1.0 and 1.5 kg VS/m(3) d, and hydraulic retention time (HRT) of 50 d. For thermophilic process, the lowest studied OLR of 1.5 kg VS/m(3) d, turned to be unstable after operation of 1.5 HRT, due to accumulating ammonia, volatile fatty acids (VFAs) and probably also long chain fatty acids (LCFAs). In conclusion, mesophilic process was found to be more feasible for co-digestion than thermophilic process, methane yields being higher and process more stable in mesophilic conditions. PMID- 22074908 TI - Artificial intelligence based modeling and optimization of poly(3-hydroxybutyrate co-3-hydroxyvalerate) production process by using Azohydromonas lata MTCC 2311 from cane molasses supplemented with volatile fatty acids: a genetic algorithm paradigm. AB - The present work describes the optimization of medium variables for the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] by Azohydromonas lata MTCC 2311 using cane molasses supplemented with propionic acid. Genetic algorithm (GA) has been used for the optimization of P(3HB-co-3HV) production through the simulation of artificial neural network (ANN) and response surface methodology (RSM). The predictions by ANN are better than those of RSM and in good agreement with experimental findings. The highest P(3HB-co-3HV) concentration and 3HV content have been reported as 7.35 g/l and 16.84 mol%, respectively by hybrid ANN-GA. Upon validation, 7.20 g/l and 16.30 mol% of P(3HB co-3HV) concentration and 3HV content have been found in the shake flask, whereas 6.70 g/l and 16.35 mol%, have been observed in a 3 l bioreactor, respectively. The specific growth rate and P(3HB-co-3HV) accumulation rate of 0.29 per h and 0.16 g/lh determined with cane molasses are comparable to those observed on pure substrates. PMID- 22074910 TI - Elucidating the role of ferrous ion cocatalyst in enhancing dilute acid pretreatment of lignocellulosic biomass. AB - BACKGROUND: Recently developed iron cocatalyst enhancement of dilute acid pretreatment of biomass is a promising approach for enhancing sugar release from recalcitrant lignocellulosic biomass. However, very little is known about the underlying mechanisms of this enhancement. In the current study, our aim was to identify several essential factors that contribute to ferrous ion-enhanced efficiency during dilute acid pretreatment of biomass and to initiate the investigation of the mechanisms that result in this enhancement. RESULTS: During dilute acid and ferrous ion cocatalyst pretreatments, we observed concomitant increases in solubilized sugars in the hydrolysate and reducing sugars in the (insoluble) biomass residues. We also observed enhancements in sugar release during subsequent enzymatic saccharification of iron cocatalyst-pretreated biomass. Fourier transform Raman spectroscopy showed that major peaks representing the C-O-C and C-H bonds in cellulose are significantly attenuated by iron cocatalyst pretreatment. Imaging using Prussian blue staining indicated that Fe2+ ions associate with both cellulose/xylan and lignin in untreated as well as dilute acid/Fe2+ ion-pretreated corn stover samples. Analyses by scanning electron microscopy and transmission electron microscopy revealed structural details of biomass after dilute acid/Fe2+ ion pretreatment, in which delamination and fibrillation of the cell wall were observed. CONCLUSIONS: By using this multimodal approach, we have revealed that (1) acid-ferrous ion-assisted pretreatment increases solubilization and enzymatic digestion of both cellulose and xylan to monomers and (2) this pretreatment likely targets multiple chemistries in plant cell wall polymer networks, including those represented by the C-O-C and C-H bonds in cellulose. PMID- 22074909 TI - Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes. AB - Catechol-O-methyltransferase (COMT) is an important enzyme in the metabolism of dopamine and disturbance in dopamine function is proposed to be central to the pathogenesis of schizophrenia. Clinical epidemiological studies have indicated cannabis use to confer a 2-fold increase in risk for subsequent onset of psychosis, with adolescent-onset use conveying even higher risk. There is evidence that a high activity COMT polymorphism moderates the effects of adolescent exposure to cannabis on risk for adult psychosis. In this paper we compared the effect of chronic adolescent exposure to the cannabinoid WIN 55212 on sensorimotor gating, behaviours related to the negative symptoms of schizophrenia, anxiety- and stress-related behaviours, as well as ex-vivo brain dopamine and serotonin levels, in COMT KO vs. wild-type (WT) mice. Additionally, we examined the effect of pretreatment with the COMT inhibitor tolcapone on acute effects of this cannabinoid on sensorimotor gating in C57BL/6 mice. COMT KO mice were shown to be more vulnerable than WT to the disruptive effects of adolescent cannabinoid treatment on prepulse inhibition (PPI). Acute pharmacological inhibition of COMT in C57BL/6 mice also modified acute cannabinoid effects on startle reactivity, as well as PPI, indicating that chronic and acute loss of COMT can produce dissociable effects on the behavioural effects of cannabinoids. COMT KO mice also demonstrated differential effects of adolescent cannabinoid administration on sociability and anxiety-related behaviour, both confirming and extending earlier reports of COMT*cannabinoid effects on the expression of schizophrenia-related endophenotypes. PMID- 22074911 TI - Virulence differences of closely related pandemic 2009 H1N1 isolates correlate with increased inflammatory responses in ferrets. AB - Several early pandemic H1N1 influenza isolates cause severe disease in different animals models, while most strains result in mild clinical signs similar to seasonal influenza. In this study, the pathogenesis of the virulent Mexican isolate A/Mexico/InDRE4487/2009 and a mild Canadian isolate A/Canada AB/RV1532/2009 was compared in ferrets. These viruses differed at nine residues, none of which has been previously identified as virulence factor. The Mexican isolate caused more severe disease and higher mortality, and reached higher peak nasal wash titers. Both viruses grew similarly in the respiratory tract, but only the virulent virus was detected in the gut after day 3. During the acute phase, both strains caused similar lung pathology, however the Mexican isolate induced severe inflammation even after virus clearance. This virus was also associated with a rapid and sustained induction of inflammatory cytokines, indicating that early dysregulation of the host response contributes importantly to the disease outcome. PMID- 22074912 TI - The influence of graphic display format on the interpretations of quantitative risk information among adults with lower education and literacy: a randomized experimental study. AB - OBJECTIVE: To test optimal graphic risk communication formats for presenting small probabilities using graphics with a denominator of 1000 to adults with lower education and literacy. METHODS: A randomized experimental study, which took place in adult basic education classes in Sydney, Australia. The participants were 120 adults with lower education and literacy. An experimental computer-based manipulation compared 1) pictographs in 2 forms, shaded "blocks" and unshaded "dots"; and 2) bar charts across different orientations (horizontal/vertical) and numerator size (small <100, medium 100-499, large 500 999). Accuracy (size of error) and ease of processing (reaction time) were assessed on a gist task (estimating the larger chance of survival) and a verbatim task (estimating the size of difference). Preferences for different graph types were also assessed. RESULTS: Accuracy on the gist task was very high across all conditions (>95%) and not tested further. For the verbatim task, optimal graph type depended on the numerator size. For small numerators, pictographs resulted in fewer errors than bar charts (blocks: odds ratio [OR] = 0.047, 95% confidence interval [CI] = 0.023-0.098; dots: OR = 0.049, 95% CI = 0.024-0.099). For medium and large numerators, bar charts were more accurate (e.g., medium dots: OR = 4.29, 95% CI = 2.9-6.35). Pictographs were generally processed faster for small numerators (e.g., blocks: 14.9 seconds v. bars: 16.2 seconds) and bar charts for medium or large numerators (e.g., large blocks: 41.6 seconds v. 26.7 seconds). Vertical formats were processed slightly faster than horizontal graphs with no difference in accuracy. Most participants preferred bar charts (64%); however, there was no relationship with performance. CONCLUSIONS: For adults with low education and literacy, pictographs are likely to be the best format to use when displaying small numerators (<100/1000) and bar charts for larger numerators (>100/1000). PMID- 22074913 TI - Repair integrity and functional outcome after arthroscopic rotator cuff repair: double-row versus suture-bridge technique. AB - BACKGROUND: Only a few studies have examined repair integrity and functional outcome after arthroscopic suture-bridge rotator cuff repair procedure. In addition, no reported study has compared outcomes between the suture-bridge and double-row techniques. PURPOSE: This study compared the functional outcome and repair integrity of arthroscopic double-row and conventional suture-bridge repair in full-thickness rotator cuff tears. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Fifty-two consecutive full-thickness rotator cuff tears with 1 to 4 cm of anterior to posterior dimension that underwent arthroscopic rotator cuff repair were included. A double-row technique was used in the first 26 consecutive shoulders, and a conventional suture-bridge technique was used in the next 26 consecutive shoulders. Fifty shoulders (92.5%) underwent magnetic resonance imaging or ultrasonography postoperatively. Clinical outcomes were evaluated a minimum 2 years (mean, 37.2 months; range, 24-54) postoperatively using the University of California at Los Angeles (UCLA), American Shoulder and Elbow Surgeons (ASES), and Constant scores. The postoperative cuff integrity was evaluated a mean of 33.0 (range, 10-54) months postoperatively. RESULTS: At the final follow-up, the average UCLA, ASES, and Constant scores improved significantly, to 32.3, 90.5, and 80.7, respectively, in the double-row group and to 30.6, 88.5, and 74.0, respectively, in the suture-bridge group. The UCLA, ASES, and Constant scores improved in both groups postoperatively (all P < .001); however, there was no significant difference between the 2 groups at final follow up (P = .185, .585, and .053, respectively). The retear rate was 24% in the shoulders that underwent double-row repair and 20% in the shoulders that underwent suture-bridge repair; this difference was not statistically significant (P = .733). CONCLUSION: The arthroscopic conventional suture-bridge technique resulted in comparable patient satisfaction, functional outcome, and rates of retear compared with the arthroscopic double-row technique in full-thickness rotator cuff tears. PMID- 22074914 TI - Morbidity and costs associated with neurological disorders. PMID- 22074916 TI - Thematic minireview series on focus on vision. PMID- 22074915 TI - KCa1.1 potassium channels regulate key proinflammatory and invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis. AB - Fibroblast-like synoviocytes (FLS) play important roles in the pathogenesis of rheumatoid arthritis (RA). Potassium channels have regulatory roles in many cell functions. We have identified the calcium- and voltage-gated KCa1.1 channel (BK, Maxi-K, Slo1, KCNMA1) as the major potassium channel expressed at the plasma membrane of FLS isolated from patients with RA (RA-FLS). We further show that blocking this channel perturbs the calcium homeostasis of the cells and inhibits the proliferation, production of VEGF, IL-8, and pro-MMP-2, and migration and invasion of RA-FLS. Our findings indicate a regulatory role of KCa1.1 channels in RA-FLS function and suggest this channel as a potential target for the treatment of RA. PMID- 22074917 TI - Multiple SecA molecules drive protein translocation across a single translocon with SecG inversion. AB - SecA is a translocation ATPase that drives protein translocation. D209N SecA, a dominant-negative mutant, binds ATP but is unable to hydrolyze it. This mutant was inactive to proOmpA translocation. However, it generated a translocation intermediate of 18 kDa. Further addition of wild-type SecA caused its translocation into either mature OmpA or another intermediate of 28 kDa that can be translocated into mature by a proton motive force. The addition of excess D209N SecA during translocation caused a topology inversion of SecG. Moreover, an intermediate of SecG inversion was identified when wild-type and D209N SecA were used in the same amounts. These results indicate that multiple SecA molecules drive translocation across a single translocon with SecG inversion. Here, we propose a revised model of proOmpA translocation in which a single catalytic cycle of SecA causes translocation of 10-13 kDa with ATP binding and hydrolysis, and SecG inversion is required when the next SecA cycle begins with additional ATP hydrolysis. PMID- 22074918 TI - Comparison of presenilin 1 and presenilin 2 gamma-secretase activities using a yeast reconstitution system. AB - gamma-Secretase is composed of at least four proteins, presenilin (PS), nicastrin (NCT), Aph1, and Pen2. PS is the catalytic subunit of the gamma-secretase complex, having aspartic protease activity. PS has two homologs, namely, PS1 and PS2. To compare the activity of these complexes containing different PSs, we reconstituted them in yeast, which lacks gamma-secretase homologs. Yeast cells were transformed with PS1 or PS2, NCT, Pen2, Aph1, and artificial substrate C55 Gal4p. After substrate cleavage, Gal4p translocates to the nucleus and activates transcription of the reporter genes ADE2, HIS3, and lacZ. gamma-Secretase activity was measured based on yeast growth on selective media and beta galactosidase activity. PS1 gamma-secretase was ~24-fold more active than PS2 gamma-secretase in the beta-galactosidase assay. Using yeast microsomes containing gamma-secretase and C55, we compared the concentration of Abeta generated by PS1 or PS2 gamma-secretase. PS1 gamma-secretase produced ~24-fold more Abeta than PS2 gamma-secretase. We found the optimal pH of Abeta production by PS2 to be 7.0, as for PS1, and that the PS2 complex included immature NCT, unlike the PS1 complex, which included mature NCT. In this study, we compared the activity of PS1 or PS2 per one gamma-secretase complex. Co-immunoprecipitation experiments using yeast microsomes showed that PS1 concentrations in the gamma secretase complex were ~28 times higher than that of PS2. Our data suggest that the PS1 complex is only marginally less active than the PS2 complex in Abeta production. PMID- 22074919 TI - Neutral sphingomyelinase 2 activity and protein stability are modulated by phosphorylation of five conserved serines. AB - We previously presented that the neutral sphingomyelinase 2 (nSMase2) is the only SMase activated in human airway epithelial (HAE) cells following exposure to oxidative stress (ox-stress), yielding ceramide accumulation and thereby inducing apoptosis. Furthermore, we reported that nSMase2 is a phospho-protein in which the level of phosphorylation controls nSMase2 activation induced by ox-stress. Here we identify five specific serines that are phosphorylated in nSMase2 and demonstrate that their phosphorylation controls the nSMase2 activity upon ox stress exposure in an interdependent manner. Furthermore, we show that the nSMase2 protein stability and thus its level of expression is also post translationally regulated by these five serine phosphorylation sites. This study provides initial structure/function insights regarding nSMase2 phosphorylation sites and offers some new links for future studies aiming to fully elucidate nSMase2 regulatory machinery. PMID- 22074920 TI - Molecular determinants of modulation of CaV2.1 channels by visinin-like protein 2. AB - CaV2.1 channels, which conduct P/Q-type Ca2+ currents, initiate synaptic transmission at most synapses in the central nervous system. Ca2+/calmodulin dependent facilitation and inactivation of these channels contributes to short term facilitation and depression of synaptic transmission, respectively. Other calcium sensor proteins displace calmodulin (CaM) from its binding site, differentially regulate CaV2.1 channels, and contribute to the diversity of short term synaptic plasticity. The neuronal calcium sensor protein visinin-like protein 2 (VILIP-2) inhibits inactivation and enhances facilitation of CaV2.1 channels. Here we examine the molecular determinants for differential regulation of CaV2.1 channels by VILIP-2 and CaM by construction and functional analysis of chimeras in which the functional domains of VILIP-2 are substituted in CaM. Our results show that the N-terminal domain, including its myristoylation site, the central alpha-helix, and the C-terminal lobe containing EF-hands 3 and 4 of VILIP 2 are sufficient to transfer its regulatory properties to CaM. This regulation by VILIP-2 requires binding to the IQ-like domain of CaV2.1 channels. Our results identify the essential molecular determinants of differential regulation of CaV2.1 channels by VILIP-2 and define the molecular code that these proteins use to control short-term synaptic plasticity. PMID- 22074921 TI - Chemistry and biology of vision. AB - Visual perception in humans occurs through absorption of electromagnetic radiation from 400 to 780 nm by photoreceptors in the retina. A photon of visible light carries a sufficient amount of energy to cause, when absorbed, a cis,trans geometric isomerization of the 11-cis-retinal chromophore, a vitamin A derivative bound to rhodopsin and cone opsins of retinal photoreceptors. The unique biochemistry of these complexes allows us to reliably and reproducibly collect continuous visual information about our environment. Moreover, other nonconventional retinal opsins such as the circadian rhythm regulator melanopsin also initiate light-activated signaling based on similar photochemistry. PMID- 22074922 TI - Determinants of the DNA binding specificity of class I and class II TCP transcription factors. AB - TCP proteins constitute a family of plant transcription factors with more than 20 members in angiosperms. They can be divided in two classes based on sequence homology and the presence of an insertion within the basic region of the TCP DNA binding and dimerization domain. Here, we describe binding site selection studies with the class I protein TCP16, showing that its DNA binding preferences are similar to those of class II proteins. Through sequence comparison and the analysis of mutants and chimeras of TCP16, TCP20 (class I), and TCP4 (class II), we established that the identity of residue 11 of the class I TCP domain or the equivalent residue 15 of the class II domain, whether it is Gly or Asp, determines a preference for a class I or a class II sequence, respectively. Footprinting analysis indicated that specific DNA contacts related to these preferences are established with one of the strands of DNA. The dimerization motif also influences the selectivity of the proteins toward class I and class II sequences and determines a requirement of an extended basic region in proteins with Asp-15. We postulate that differences in orientation of base-contacting residues brought about by the presence of either Gly or Asp are responsible for the binding site preferences of TCP proteins. Expression of repressor forms of TCP16 with Asp-11 or Gly-11 differently affects leaf development. TCP16-like proteins with Asp-11 in the TCP domain arose in rosids and may be related to developmental characteristics of this lineage of eudicots. PMID- 22074923 TI - MicroRNA 34c gene down-regulation via DNA methylation promotes self-renewal and epithelial-mesenchymal transition in breast tumor-initiating cells. AB - Tumor-initiating cells (T-ICs), a subpopulation of cancer cells with stem cell like properties, are related to tumor relapse and metastasis. Our previous studies identified a distinct profile of microRNA (miRNA) expression in breast T ICs (BT-ICs), and the dysregulated miRNAs contribute to the self-renewal and tumorigenesis of these cells. However, the underlying mechanisms for miRNA dysregulation in BT-ICs remain obscure. In the present study, we demonstrated that the expression and function of miR-34c were reduced in the BT-ICs of MCF-7 and SK-3rd cells, a breast cancer cell line enriched for BT-ICs. Ectopic expression of miR-34c reduced the self-renewal of BT-ICs, inhibited epithelial mesenchymal transition, and suppressed migration of the tumor cells via silencing target gene Notch4. Furthermore, we identified a single hypermethylated CpG site in the promoter region of miR-34c gene that contributed to transcriptional repression of miR-34c in BT-ICs by reducing DNA binding activities of Sp1. Therefore, miR-34c reduction in BT-ICs induced by a single hypermethylated CpG site in the promoter region promotes self-renewal and epithelial-mesenchymal transition of BT-ICs. PMID- 22074924 TI - Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles. AB - Inappropriate clearance of apoptotic remnants is considered to be the primary cause of systemic autoimmune diseases, like systemic lupus erythematosus. Here we demonstrate that apoptotic cells release distinct types of subcellular membranous particles (scMP) derived from the endoplasmic reticulum (ER) or the plasma membrane. Both types of scMP exhibit desialylated glycotopes resulting from surface exposure of immature ER-derived glycoproteins or from surface-borne sialidase activity, respectively. Sialidase activity is activated by caspase dependent mechanisms during apoptosis. Cleavage of sialidase Neu1 by caspase 3 was shown to be directly involved in apoptosis-related increase of surface sialidase activity. ER-derived blebs possess immature mannosidic glycoepitopes and are prioritized by macrophages during clearance. Plasma membrane-derived blebs contain nuclear chromatin (DNA and histones) but not components of the nuclear envelope. Existence of two immunologically distinct types of apoptotic blebs may provide new insights into clearance-related diseases. PMID- 22074925 TI - Photoreceptor signaling: supporting vision across a wide range of light intensities. AB - For decades, photoreceptors have been an outstanding model system for elucidating basic principles in sensory transduction and biochemistry and for understanding many facets of neuronal cell biology. In recent years, new knowledge of the kinetics of signaling and the large-scale movements of proteins underlying signaling has led to a deeper appreciation of the photoreceptor's unique challenge in mediating the first steps in vision over a wide range of light intensities. PMID- 22074926 TI - Identification and structural characterization of novel cyclotide with activity against an insect pest of sugar cane. AB - Cyclotides are a family of plant-derived cyclic peptides comprising six conserved cysteine residues connected by three intermolecular disulfide bonds that form a knotted structure known as a cyclic cystine knot (CCK). This structural motif is responsible for the pronounced stability of cyclotides against chemical, thermal, or proteolytic degradation and has sparked growing interest in this family of peptides. Here, we isolated and characterized a novel cyclotide from Palicourea rigida (Rubiaceae), which was named parigidin-br1. The sequence indicated that this peptide is a member of the bracelet subfamily of cyclotides. Parigidin-br1 showed potent insecticidal activity against neonate larvae of Lepidoptera (Diatraea saccharalis), causing 60% mortality at a concentration of 1 MUm but had no detectable antibacterial effects. A decrease in the in vitro viability of the insect cell line from Spodoptera frugiperda (SF-9) was observed in the presence of parigidin-br1, consistent with in vivo insecticidal activity. Transmission electron microscopy and fluorescence microscopy of SF-9 cells after incubation with parigidin-br1 or parigidin-br1-fluorescein isothiocyanate, respectively, revealed extensive cell lysis and swelling of cells, consistent with an insecticidal mechanism involving membrane disruption. This hypothesis was supported by in silico analyses, which suggested that parigidin-br1 is able to complex with cell lipids. Overall, the results suggest promise for the development of parigidin-br1 as a novel biopesticide. PMID- 22074927 TI - Metabolism of carotenoids and retinoids related to vision. AB - All animals endowed with the ability to detect light through visual pigments must have evolved pathways in which dietary precursors for the involved chromophore are absorbed, transported, and metabolized. Knowledge about this metabolism has exponentially increased over the past decade. Genetic manipulation of animal models provided insights into the metabolic flow of these compounds through the body and in the eyes, unraveling their regulatory aspects and aberrant side reactions. The scheme that emerges reveals a common origin of key components for chromophore metabolism that have been adapted to the specific requirements of retinoid biology in different animal classes. PMID- 22074928 TI - Rod and cone visual pigments and phototransduction through pharmacological, genetic, and physiological approaches. AB - Activation of the visual pigment by light in rod and cone photoreceptors initiates our visual perception. As a result, the signaling properties of visual pigments, consisting of a protein, opsin, and a chromophore, 11-cis-retinal, play a key role in shaping the light responses of photoreceptors. The combination of pharmacological, physiological, and genetic tools has been a powerful approach advancing our understanding of the interactions between opsin and chromophore and how they affect the function of visual pigments. The signaling properties of the visual pigments modulate many aspects of the function of rods and cones, producing their unique physiological properties. PMID- 22074929 TI - Loss of daylight vision in retinal degeneration: are oxidative stress and metabolic dysregulation to blame? AB - Retinitis pigmentosa is characterized by loss of night vision, followed by complete blindness. Over 40 genetic loci for retinitis pigmentosa have been identified in humans, primarily affecting photoreceptor structure and function. The availability of excellent animal models allows for a mechanistic characterization of the disease. Metabolic dysregulation and oxidative stress have been found to correlate with the loss of vision, particularly in cones, the type of photoreceptors that mediate daylight and color vision. The evidence that these problems actually cause loss of vision and potential therapeutic approaches targeting them are discussed. PMID- 22074930 TI - Melanopsin and mechanisms of non-visual ocular photoreception. AB - In addition to rods and cones, the mammalian eye contains a third class of photoreceptor, the intrinsically photosensitive retinal ganglion cell (ipRGC). ipRGCs are heterogeneous irradiance-encoding neurons that primarily project to non-visual areas of the brain. Characteristics of ipRGC light responses differ significantly from those of rod and cone responses, including depolarization to light, slow on- and off-latencies, and relatively low light sensitivity. All ipRGCs use melanopsin (Opn4) as their photopigment. Melanopsin resembles invertebrate rhabdomeric photopigments more than vertebrate ciliary pigments and uses a G(q) signaling pathway, in contrast to the G(t) pathway used by rods and cones. ipRGCs can recycle chromophore in the absence of the retinal pigment epithelium and are highly resistant to vitamin A depletion. This suggests that melanopsin employs a bistable sequential photon absorption mechanism typical of rhabdomeric opsins. PMID- 22074931 TI - The prognostic value of serial leukocyte adhesion molecules in post-aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Leukocyte recruitment and inflammatory response play an important role in the pathophysiology after aneurysmal subarachnoid hemorrhage (SAH). We determined whether leukocyte adhesion molecules after aneurysmal SAH can predict the presence of delayed cerebral infarction (DCI). METHODS: Serial changes in P selectin glycoprotein ligand-1 (PSGL-1), macrophage antigen-1 (Mac-1), and lymphocyte function-associated antigen-1 (LFA-1) expression by leukocyte subsets were prospectively examined using flow cytometry at various time points in 20 acute aneurysmal SAH patients and 21 healthy volunteers who were free of medications were enrolled as a control group. RESULTS: Neutrophil (cut-off value of >44.90) and monocyte (cut-off value of >32.95) PSGL-1 expressions on admission were significantly higher in patients with DCI than in non-DCI patients, but the difference between neutrophil PGSL-1 and monocyte PGSL-1 levels between the two groups was no longer significant from Day 4 to Day 14 after aneurysmal SAH. After stepwise logistic regression analysis, only neutrophil PSGL-1 expression upon admission was independently associated with DCI. The mean hospitalization days were 44.4+/-26.2 for those patients with DCI and 40.5+/-26.4 for non-DCI patients. After a minimum 6-month follow-up period, the median BI score was 20 for DCI patients and 80 for non-DCI patients. CONCLUSIONS: Higher expressions of neutrophil PSGL-1 on admission may imply a danger of DCI in patients with aneurysmal SAH. PMID- 22074932 TI - Isolation of Coxsackievirus A24 variant from patients with hemorrhagic conjunctivitis in Cuba, 2008-2009. AB - BACKGROUND: An outbreak of acute hemorrhagic conjunctivitis occurred in Cuba in 2008 and 2009. OBJECTIVE: To determinate the etiological agent associated with the Cuban outbreaks of acute hemorrhagic conjunctivitis during 2008 and 2009. STUDY DESIGN: Conjunctival swabs and/or faecal samples from 382 patients with clinical diagnosis suggestive of acute hemorrhagic conjunctivitis were subject to viral culture in HEp-2 human laryngeal epidermoid carcinoma cells. Positive samples were identified by a specific Coxsackievirus A24 variant PCR and the 3C protease region of 16 isolates was sequenced for phylogenetic analysis. RESULTS: Enterovirus cytopathic effect was observed in 138 cases (36%). A higher percent of CA24v was recovered from faecal samples, 19 out of 45 cases (42.2%), than from conjunctival swabs, 127 out of 355 samples (35.8%). All isolates were identified as Coxsackievirus A24 variant. Phylogenetic analysis revealed that 2008 and 2009 Cuban outbreaks were caused by the same virus strains and that isolates were closely related to those from Taiwan (2006-2007), China (2007-2008) and Singapore (2005) with a bootstrap value of 71%. CONCLUSIONS: Outbreaks of acute hemorrhagic conjunctivitis occurred in Cuba in 2008 and 2009 were caused by Coxsackievirus A24 variant. The faecal-oral route is another mode of transmission of CA24v in the acute hemorrhagic conjunctivitis outbreaks. Phylogenetic analysis of Cuban CA24v strains involved in an acute hemorrhagic conjunctivitis outbreak in 2008 and 2009 confirms a new introduction of the CA24 variant into the Americas from South-east Asia. PMID- 22074933 TI - Susceptibility to varicella-zoster among pregnant women in the province of Lecce, Italy. AB - BACKGROUND: Varicella is predominantly a childhood disease, considered a mild self-limiting disease that can have serious complications for a pregnant woman and her developing fetus. OBJECTIVES: We investigated the susceptibility to varicella-zoster Virus (VZV) among pregnant women in the province of Lecce. STUDY DESIGN: A cross-sectional study was carried out in Departments of Gynecology and Obstetrics of the Province of Lecce, where 539 pregnant women were recruited, and face-to-face interviews were conducted. Varicella IgG tests were performed. RESULTS: The prevalence of varicella susceptibility among pregnant mothers was 10.6%. The prevalence of IgG antibodies increases significantly with increasing age, from 62.5% in the age group 15-19 years to 94.4% in the age group 40-49 years. DISCUSSION: In the Italian National Vaccination Plan 2005-2007, varicella vaccine is only recommended for childbearing women. A safe and effective vaccine is available and no abnormalities have been observed among infants born to susceptible women who received varicella vaccines during pregnancy. Such a high number of susceptible women indicates that preventive and informative programs should be introduced, even among those who do not plan to become pregnant. Routine counselling, varicella IgG antibody screening and varicella vaccination should be considered if they have no history of the infection, to reduce the risk of fetal complications and the cost of healthcare associated with the infection. PMID- 22074935 TI - Introducing the parvome: bioactive compounds in the microbial world. AB - We describe and discuss the features and functions of the "parvome", the "-ome" of the chemical world, consisting of the small molecules produced by living organisms. Here, we focus specifically on the world of microbial small molecules. Many years of natural product discovery research, coupled with recent advances and applications of genetic and genomic techniques have revealed the presence of an enormous collection of unique small molecules that are the products of cellular metabolism. As yet, we have a poor understanding of their functions and, in most cases, little knowledge of their routes of biosynthesis, although such information is accruing rapidly. In this review, we attempt to address the raison d'etre of the parvome in the bacterial world, and we propose that a better understanding of the true biological roles of natural products will permit the application of rational approaches to the more effective exploitation of their use in medicine by humankind. PMID- 22074934 TI - Ten years of human metapneumovirus research. AB - Described for the first time in 2001, human metapneumovirus (hMPV) has become one of the main viral pathogens responsible for acute respiratory tract infections in children but also in the elderly and immuno-compromised patients. The pathogen most closely related to hMPV is human respiratory syncytial virus (hRSV), the most common cause of bronchiolitis and pneumonia in young children. hMPV has been classified into two main viral groups A and B and has a seasonal distribution in temperate countries with most cases occurring in winter and spring. Given the difficulties encountered in culturing hMPV in vitro, diagnosis is generally achieved using real-time polymerase chain reaction. Like other Paramyxoviridae, hMPV has a negative-sense single-stranded RNA genome that includes 8 genes coding for 9 different proteins. The genomic organization and functions of surface attachment and fusion glycoproteins are relatively similar to those of hRSV. Although many groups have studied the viral life cycle of hMPV, many questions remain unanswered concerning the exact roles of the viral proteins in the attachment, fusion and replication of hMPV. To date, there remains no approved modality to combat hMPV infections. The majority of treatments that have been tested on hMPV have already demonstrated activity against hRSV infections. Some innovative approaches based on RNA interference and on fusion inhibitors have shown efficacy in vitro and in animal studies and could be beneficial in treating human hMPV disease. Difficulties faced inducing a durable immune response represent the biggest challenge in the development of an effective hMPV vaccine. Several strategies, such as the use of live-attenuated viruses generated by reverse genetics or recombinant proteins, have been tested in animals with encouraging results. PMID- 22074937 TI - Multifocal skin lesions and melena with thrombocytopenia in an infant. PMID- 22074938 TI - Applications of cathodoluminescence spectroscopy and imaging in the characterisation of pharmaceutical materials. AB - Cathodoluminescence (CL) analysis is a mature technique which utilises the light that is emitted from materials when they are bombarded with a beam of high energy electrons to produce spectra and spectral images of specimens. This technique is used routinely in many industries as a non-destructive way to investigate and characterise inorganic compounds, such as minerals, ceramics and semiconductors, as they are being examined in a scanning electron microscope, but is seldom used to study organic compounds. The discovery that many (up to about 80%) active pharmaceutical ingredients (APIs) and API-like compounds are cathodoluminescent has resulted in the development of CL analysis as a novel technique to rapidly visualise the solid state spatial distribution of APIs in drug products as they are being examined by scanning electron microscopy. Spectral images of API particles dispersed in drug products (a tablet, a multiparticulate bead, and a dry powder inhalation blend) were acquired to illustrate the practical application of CL imaging to support product development or to optimise manufacturing processes. This study has also revealed that CL spectroscopy can distinguish between crystalline and amorphous materials and is sensitive the differences between the solid forms of some organic compounds, such as salts and polymorphs. Up to 80% of commonly used excipients are non-cathodoluminescent and this has the advantage of enabling APIs in formulated products to be imaged without interference. As part of the investigation to explore the use of CL as a way to identify polymorphs and monitor phase transformations, it was discovered that by recrystallising fused carbamazepine, the metastable Form IV was unexpectedly produced. PMID- 22074939 TI - Mapping Patient-Specific Functional Scale (PSFS) items to the International Classification of Functioning, Disability and Health (ICF). AB - BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) provides a common framework for clinical outcome measurement. Because the Patient-Specific Functional Scale (PSFS) is widely used for documenting change over time in individual patients receiving musculoskeletal physical therapy, investigation of the extent to which PSFS items reflect the ICF is needed. OBJECTIVE: The study objective was to investigate the extent to which patient-generated PSFS items reflect ICF domains. DESIGN: This investigation was an observational content validity study. METHODS: A total of 2,911 PSFS items from 1,050 files for patients with musculoskeletal disorders were analyzed. The data were from a random sample of participants in the Otago Outcome Measures Project at 4 clinics of the School of Physiotherapy, University of Otago, situated in 3 New Zealand cities. Patient-nominated PSFS items were categorized and mapped with thematic analysis techniques to ICF components, chapters, and categories. Subgroup analyses were conducted for body region of injury and age ranges. RESULTS: All (100%) of the analyzed items could be mapped to the ICF. Most patient-nominated items mapped to the activity component (80.0%), some items mapped to the participation component (7.7%), other items were related to impairment (7.4%), and the fourth group contained items that overlapped the activity and participation components (4.9%). Similar results were found for each of the 5 body regions and across age ranges in subgroup analyses. LIMITATIONS: These results are limited to individual patients seeking musculoskeletal physical therapy. Patient-generated PSFS items were investigated. CONCLUSIONS: The ICF activity component was most commonly represented by patient-nominated PSFS items, the participation component was moderately represented, and impairment was least represented. Hence, the PSFS would complement impairment-based clinical outcome measures. PMID- 22074940 TI - The modified Gait Efficacy Scale: establishing the psychometric properties in older adults. AB - BACKGROUND: Perceived ability or confidence plays an important role in determining function and behavior. The modified Gait Efficacy Scale (mGES) is a 10-item self-report measure used to assess walking confidence under challenging everyday circumstances. OBJECTIVE: The purpose of this study was to determine the reliability, internal consistency, and validity of the mGES as a measure of gait in older adults. DESIGN: This was a cross-sectional study. METHODS: Participants were 102 community-dwelling older adults (mean [+/-SD] age=78.6+/-6.1 years) who were independent in ambulation with or without an assistive device. Participants were assessed using the mGES and measures of confidence and fear, measures of function and disability, and performance-based measures of mobility. In a subsample (n=26), the mGES was administered twice within a 1-month period to establish test-retest reliability through the intraclass correlation coefficient (ICC [2,1]). The standard error of measure (SEM) was determined from the ICC and standard deviation. The Cronbach alpha value was calculated to determine internal consistency. To establish the validity of the mGES, the Spearman rank order correlation coefficient was used to examine the association with measures of confidence, fear, gait, and physical function and disability. RESULTS: The mGES demonstrated test-retest reliability within the 1-month period (ICC=.93, 95% confidence interval=.85, .97). The SEM of the mGES was 5.23. The mGES was internally consistent across the 10 items (Cronbach alpha=.94). The mGES was related to measures of confidence and fear (r=.54-.88), function and disability (Late-Life Function and Disability Instrument, r=.32-.88), and performance-based mobility (r=.38-.64). LIMITATIONS: This study examined only community-dwelling older adults. The results, therefore, should not be generalized to other patient populations. CONCLUSION: The mGES is a reliable and valid measure of confidence in walking among community-dwelling older adults. PMID- 22074941 TI - Continuity in the provider of home-based physical therapy services and its implications for outcomes of patients. AB - BACKGROUND: A growing body of research suggests that greater continuity of health care is positively associated with improved outcomes of patients. However, few studies have examined this issue in the context of physical therapy. OBJECTIVE: The purpose of this study was to evaluate whether the level of continuity in the provider (provider continuity) of physical therapy services was related to outcomes in a population of patients receiving home health care. DESIGN: This was a retrospective observational study. METHODS: Clinical and administrative records were retrieved for a population of adult patients receiving physical therapy services from a large, urban, not-for-profit certified home health care agency in 2009. Descriptive and multivariable analyses were used to examine how the level of provider continuity, calculated by use of a formula that models dispersion in contact between the patient and the providers of physical therapy services, varied across characteristics and outcomes of patients. RESULTS: Logistic regression analyses indicated that patients with lower levels of provider continuity had significantly higher odds of hospitalization (odds ratio [OR]=2.06, 95% confidence interval [CI]=1.90-2.23) and lower odds of improvements in the number of activity limitations (OR=0.85, 95% CI=0.80-0.92) and in the severity of activity limitations (OR=0.85, 95% CI=0.78-0.93) between the beginning and the end of the home health care episode. LIMITATIONS: Baseline clinical characteristics associated with continuity of care suggest some level of indication bias. Outcome measures for activities of daily living were limited to patients who were not hospitalized during their home health stay. CONCLUSIONS: These findings build upon research suggesting that continuity in the patient provider relationship is an important determinant of outcomes of patients. PMID- 22074942 TI - Protease inhibitors for treatment of genotype 1 hepatitis C virus infection. PMID- 22074943 TI - Achieving integrated care is a slow and difficult process. PMID- 22074944 TI - Ombudsman reports GP to the GMC for refusing to apologise to a patient. PMID- 22074945 TI - Single maintenance and reliever therapy (SMART) for asthma. AB - Around 5.2 million people in the UK are estimated to have asthma.1 Mortality and hospitalisation rates associated with the condition fell significantly in the last 20 years of the 20th century, but have not fallen further since then.2 In 2006, there were over 1,000 asthma deaths and around 78,000 hospital admissions due to asthma in the UK.2 One pharmacological strategy that has been developed recently to try to improve asthma management is the use of single maintenance and reliever therapy (SMART). This involves the patient using a single inhaler containing a corticosteroid (budesonide) and a long-acting beta(2) agonist (LABA; formoterol), for regular maintenance treatment, but also for additional 'rescue' use on an as-needed basis. Combination inhaler use is claimed to improve adherence, and is now included in UK asthma guidelines.3 Here we assess the evidence for single combination therapy, its relative effectiveness in comparison with other approaches, and whether or under what circumstances it should be used. PMID- 22074946 TI - Tyrosine kinase inhibitors for metastatic renal cell carcinoma. AB - Renal cell carcinoma accounts for 2-3% of all adult malignancies worldwide, and around 30% of patients with the condition present with advanced or metastatic disease.1,2 Until recently, cytokine therapy (e.g. interleukin-2 or interferon alfa) was the standard treatment for metastatic renal cell carcinoma but provided only a small survival advantage (e.g. extending life by a median of 2.5 months).3 A key development has been the introduction of drugs known as receptor tyrosine kinase inhibitors, which include ?sunitinib (Sutent-Pfizer), ?sorafenib (Nexavar Bayer) and ?pazopanib (Votrient-GlaxoSmithKline). Here we review the evidence on the efficacy, tolerability and cost-effectiveness of these treatments in renal cell carcinoma. PMID- 22074947 TI - Research resource: enhanced genome-wide occupancy of estrogen receptor alpha by the cochaperone p23 in breast cancer cells. AB - p23 is a chaperone with multiple heat shock protein 90 dependent and independent cellular functions, including stabilizing unliganded steroid receptors and modulating receptor-DNA dynamics. p23 protein is also up-regulated in several cancers, notably breast cancer. We previously demonstrated that higher expression of p23 in the estrogen-dependent breast cancer line MCF-7 (MCF-7+p23) selectively increased estrogen receptor (ER) target gene transcription and ER recruitment to regulatory elements, promoted cell invasion, and predicted a poor prognosis in breast cancer patients. To probe the impact of p23 on ER binding throughout the human genome, we compared ER occupancy in MCF-7+p23 cells relative to MCF-7 control cells by using chromatin immunoprecipitation followed by ultrahigh throughput DNA sequencing in the absence and presence of 17beta-estradiol (E2) treatment. We found that increased expression of p23 resulted in a 230% increase in the number of E2-induced ER-binding sites throughout the genome compared with control cells and also increased ER binding under basal conditions. Motif analysis indicated that ER binds to a similar DNA sequence regardless of p23 status. We also observed that ER tends to bind closer to genes that were induced, rather than repressed by either E2 treatment or p23 overexpression. Interestingly, we also found that the increased invasion of MCF-7+p23 cells was not only p23 dependent but also ER dependent. Thus, a small increase in the expression of p23 amplifies ER-binding genome wide and, in combination with ER, elicits an invasive phenotype. This makes p23 an attractive target for combating tumor cell metastasis in breast cancer patients. PMID- 22074948 TI - Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor. AB - Mouse resistin, a cysteine-rich protein primarily secreted from mature adipocytes, is involved in insulin resistance and type 2 diabetes. Human resistin, however, is mainly secreted by immune mononuclear cells, and it competes with lipopolysaccharide for the binding to Toll-like receptor 4, which could mediate some of the well-known proinflammatory effects of resistin in humans. In addition, resistin has been involved in the regulation of many cell differentiation and proliferation processes, suggesting that different receptors could be involved in mediating its numerous effects. Thus, a recent work identifies an isoform of Decorin (Delta Decorin) as a functional resistin receptor in adipocyte progenitors that may regulate white adipose tissue expansion. Our work shows that the mouse receptor tyrosine kinase-like orphan receptor (ROR)1 could mediate some of the described functions of resistin in 3T3 L1 adipogenesis and glucose uptake. We have demonstrated an interaction of mouse resistin with specific domains of the extracellular region of the ROR1 receptor. This interaction results in the inhibition of ROR1 phosphorylation, modulates ERK1/2 phosphorylation, and regulates suppressor of cytokine signaling 3, glucose transporter 4, and glucose transporter 1 expression. Moreover, mouse resistin modulates glucose uptake and promotes adipogenesis of 3T3-L1 cells through ROR1. In summary, our results identify mouse resistin as a potential inhibitory ligand for the receptor ROR1 and demonstrate, for the first time, that ROR1 plays an important role in adipogenesis and glucose homeostasis in 3T3-L1 cells. These data open a new line of research that could explain important questions about the resistin mechanism of action in adipogenesis and in the development of insulin resistance. PMID- 22074949 TI - BMP3 suppresses osteoblast differentiation of bone marrow stromal cells via interaction with Acvr2b. AB - Enhancing bone morphogenetic protein (BMP) signaling increases bone formation in a variety of settings that target bone repair. However, the role of BMP in the maintenance of adult bone mass is not well understood. Targeted disruption of BMP3 in mice results in increased trabecular bone formation, whereas transgenic overexpression of BMP3 in skeletal cells leads to spontaneous fracture, consistent with BMP3 having a negative role in bone mass regulation. Here we investigate the importance of BMP3 as a mediator of BMP signaling in the adult skeleton. We find that osteoblasts (OBL) and osteocytes are the source of BMP3 in adult bone. Using in vitro cultures of primary bone marrow stromal cells, we show that overexpression of BMP3 suppresses OBL differentiation, whereas loss of BMP3 increases colony-forming unit fibroblasts and colony-forming unit OBL. The ability of BMP3 to affect OBL differentiation is due to its interaction with activin receptor type 2b (Acvr2b) because knockdown of endogenous Acvr2b in bone marrow stromal cells reduces the suppressive effect of BMP3 on OBL differentiation. These findings best fit a model in which BMP3, produced by mature bone cells, acts to reduce BMP signaling through Acvr2b in skeletal progenitor cells, limiting their differentiation to mature OBL. Our data further support the idea that endogenous BMPs have a physiological role in regulating adult bone mass. PMID- 22074950 TI - Research resource: transcriptional response to glucocorticoids in childhood acute lymphoblastic leukemia. AB - Glucocorticoids (GC) induce apoptosis in lymphoblasts and are thus essential in the treatment of acute lymphoblastic leukemia (ALL). Their effects result from gene regulations via the GC receptor (NR3C1/GR), but it is unknown how these changes evolve, what the primary GR targets are, and to what extent responses differ between ALL subtypes and nonlymphoid malignancies. We delineated the transcriptional response to GC on the exon level in a time-resolved manner in a precursor B- and a T childhood ALL model employing Exon microarrays and combined this with genome-wide NR3C1-binding site detection using chromatin immunoprecipitation-on-chip technology. This integrative approach showed that the response was strongly influenced by kinetics and extent of GR autoinduction in both models. Although remarkable differences between the ALL systems were apparent, we defined a set of common response genes enriched in apoptosis-related processes. Globally, GR binding was higher for GC-induced vs. -repressed genes, suggesting that GR mediates gene repression by interaction with distant enhancers or by cross talk with other transcription factors. Exon level analysis defined several new GC-regulated transcript variants of genes, including ATP4B, GPR98, TBCD, and ZBTB16. Our study provides unprecedented insight into the transcriptional response to GC in ALL cells, essential to understand this biologically and clinically important phenomenon. We found evidence of cell type specific as well as common responses, possibly related to apoptosis induction, and detected induction of novel transcript variants by GC in the investigated systems. Finally, we implemented a bioinformatic framework that might be useful for high-density microarray analyses to identify alternative transcript variant expression. PMID- 22074951 TI - Research resource: interactome of human embryo implantation: identification of gene expression pathways, regulation, and integrated regulatory networks. AB - A prerequisite for successful embryo implantation is adequate preparation of receptive endometrium and the establishment and maintenance of a viable embryo. The success of implantation further relies upon a two-way dialogue between the embryo and uterus. However, molecular bases of these preimplantation and implantation processes in humans are not well known. We performed genome expression analyses of human embryos (n = 128) and human endometria (n = 8). We integrated these data with protein-protein interactions in order to identify molecular networks within the endometrium and the embryo, and potential embryo endometrium interactions at the time of implantation. For that, we applied a novel network profiling algorithm HyperModules, which combines topological module identification and functional enrichment analysis. We found a major wave of transcriptional down-regulation in preimplantation embryos. In receptive-stage endometrium, several genes and signaling pathways were identified, including JAK STAT signaling and inflammatory pathways. The main curated embryo-endometrium interaction network highlighted the importance of cell adhesion molecules in the implantation process. We also identified cytokine-cytokine receptor interactions involved in implantation, where osteopontin (SPP1), leukemia inhibitory factor (LIF) and leptin (LEP) pathways were intertwining. Further, we identified a number of novel players in human embryo-endometrium interactions, such as apolipoprotein D (APOD), endothelin 1 (END1), fibroblast growth factor 7 (FGF7), gastrin (GAST), kringle containing trnasmembrane protein 1 (KREMEN1), neuropilin 1 (NRP1), serpin peptidase inhibitor clade A member 3 (SERPINA3), versican (VCAN), and others. Our findings provide a fundamental resource for better understanding of the genetic network that leads to successful embryo implantation. We demonstrate the first systems biology approach into the complex molecular network of the implantation process in humans. PMID- 22074952 TI - Androgen receptor repression of GnRH gene transcription. AB - Alterations in androgen levels lead to reproductive defects in both males and females, including hypogonadotropic hypogonadism, anovulation, and infertility. Androgens have been shown to down-regulate GnRH mRNA levels through an androgen receptor (AR)-dependent mechanism. Here, we investigate how androgen regulates expression from the GnRH regulatory region in the GT1-7 cell line, a model of GnRH neurons. A synthetic androgen, R1881, repressed transcription from the GnRH promoter (GnRH-P) in an AR-dependent manner, and liganded AR associated with the chromatin at the GnRH-P in live GT1-7 cells. The three known octamer-binding transcription factor-1 (Oct-1) binding sites in GnRH-P were required for AR mediated repression, although other sequences were also involved. Although a multimer of the consensus Oct-1 binding site was not repressed, a multimer of the cluster of Oct-1, Pre-B cell leukemia transcription factor (Pbx)/Prep, and NK2 homeobox 1 (Nkx2.1) binding sites, found at -106/-91 in GnRH-P, was sufficient for repression. In fact, overexpression of any of these factors disrupted the androgen response, indicating that a balance of factors in this tripartite complex is required for AR repression. AR bound to this region in EMSA, indicating a direct interaction of AR with DNA or with other transcription factors bound to GnRH-P at this sequence. Collectively, our data demonstrate that GnRH transcription is repressed by AR via multiple sequences in GnRH-P, including three Oct-1 binding sites, and that this repression requires the complex interaction of several transcription factors. PMID- 22074954 TI - Molecular determinants of the interaction between human high molecular weight kininogen and Candida albicans cell wall: Identification of kininogen-binding proteins on fungal cell wall and mapping the cell wall-binding regions on kininogen molecule. AB - An excessive production of vasoactive and proinflammatory bradykinin-related peptides, the kinins, is often involved in the human host defense against microbial infections. Recent studies have shown that a major fungal pathogen to humans, Candida albicans, can bind the proteinaceous kinin precursor, the high molecular weight kininogen (HK) and trigger the kinin-forming cascade on the cell surface. In this work, we preliminarily characterized a molecular mechanism underlying the HK adhesion to the fungal surface by (i) identification of major kininogen-binding constituents on the candidial cell wall and (ii) mapping the cell wall-binding regions on HK molecule. A major fraction of total fungal kininogen-binding capacity was assigned to beta-1,3-glucanase-extractable cell wall proteins (CWP). By adsorption of CWP on HK-coupled agarose gel and mass spectrometric analysis of the eluted material, major putative HK receptors were identified, including Als3 adhesin and three glycolytic enzymes, i.e., enolase 1, phosphoglycerate mutase 1 and triosephosphate isomerase 1. Using monoclonal antibodies directed against selected parts of HK molecule and synthetic peptides with sequences matching selected HK fragments, we assigned the major fungal cell wall-binding ability to a short stretch of amino acids in the C-terminal part of domain 3 and a large continuous region involving the C-terminal part of domain 5 and N-terminal part of domain 6 (residues 479-564). The latter characteristics of HK binding to C. albicans surface differ from those reported for bacteria and host cells. PMID- 22074953 TI - Evolutionary history and functional characterization of the amphibian xenosensor CAR. AB - The xenosensing constitutive androstane receptor (CAR) is widely considered to have arisen in early mammals via duplication of the pregnane X receptor (PXR). We report that CAR emerged together with PXR and the vitamin D receptor from an ancestral NR1I gene already in early vertebrates, as a result of whole-genome duplications. CAR genes were subsequently lost from the fish lineage, but they are conserved in all taxa of land vertebrates. This contrasts with PXR, which is found in most fish species, whereas it is lost from Sauropsida (reptiles and birds) and plays a role unrelated to xenosensing in Xenopus. This role is fulfilled in Xenopus by CAR, which exhibits low basal activity and pronounced responsiveness to activators such as drugs and steroids, altogether resembling mammalian PXR. The constitutive activity typical for mammalian CAR emerged first in Sauropsida, and it is thus common to all fully terrestrial land vertebrates (Amniota). The constitutive activity can be achieved by humanizing just two amino acids of the Xenopus CAR. Taken together, our results provide a comprehensive reconstruction of the evolutionary history of the NR1I subfamily of nuclear receptors. They identify CAR as the more conserved and remarkably plastic NR1I xenosensor in land vertebrates. Nonmammalian CAR should help to dissect the specific functions of PXR and CAR in the metabolism of xeno- and endobiotics in humans. Xenopus CAR is a first reported amphibian xenosensor, which opens the way to toxicogenomic and bioaugmentation studies in this critically endangered taxon of land vertebrates. PMID- 22074955 TI - Beyond the metabolic role of ghrelin: a new player in the regulation of reproductive function. AB - Ghrelin is a gastric peptide, discovered by Kojima et al. (1999) [55] as a result of the search for an endogenous ligand interacting with the "orphan receptor" GHS R1a (growth hormone secretagogue receptor type 1a). Ghrelin is composed of 28 aminoacids and is produced mostly by specific cells of the stomach, by the hypothalamus and hypophysis, even if its presence, as well as that of its receptors, has been demonstrated in many other tissues, not least in gonads. Ghrelin potently stimulates GH release and participates in the regulation of energy homeostasis, increasing food intake, decreasing energy output and exerting a lipogenetic effect. Furthermore, ghrelin influences the secretion and motility of the gastrointestinal tract, especially of the stomach, and, above all, profoundly affects pancreatic functions. Despite of these previously envisaged activities, it has recently been hypothesized that ghrelin regulates several aspects of reproductive physiology and pathology. In conclusion, ghrelin not only cooperates with other neuroendocrine factors, such as leptin, in the modulation of energy homeostasis, but also has a crucial role in the regulation of the hypothalamic-pituitary gonadal axis. In the current review we summarize the main targets of this gastric peptide, especially focusing on the reproductive system. PMID- 22074956 TI - Pharmacological characteristics of endokinin C/D-derived peptides in nociceptive and inflammatory processing in rats. AB - Endokinins designated from the human TAC4 gene consist of endokinin A, endokinin B, endokinin C (EKC) and endokinin D (EKD). EKC/D is a peptide using the common carboxyl-terminal in EKC and EKD and consists of 12 amino acids, and exerts antagonistic effects on the induction of scratching behavior by substance P (SP). Some of SP-preferring receptor antagonists have several d-tryptophan (d-Trp); however, the pharmacological effect of EKC/D-derived peptides with d-Trp remains to be solved. Therefore, to clarify the pharmacological characteristics of EKC/D derived peptides, effects of pretreatment with these peptides on SP-induced scratching and thermal hyperalgesia, formalin-induced flinching and carrageenan induced inflammation were evaluated. Intrathecal administration of [d-Trp(8)] EKC/D and [d-Trp(10)]-EKC/D showed a markedly long inhibitory effect, at least 14 h, whereas the antagonistic effects of [d-Trp(8,10)]-EKC/D and EKC/D without d Trp disappeared after 1h. Furthermore, the inhibitory effect of [d-Trp(10)]-EKC/D derived peptides was dependent on the number of amino acids from the amino terminus, and the more numerous the amino acids, the more marked the antagonistic effect. Thus, these results indicate that the effective duration of EKC/D-derived peptides is dependent on the number of d-Trp in the carboxyl-terminal region and the amino-terminal region regulates the antagonistic effect of EKC/D. PMID- 22074957 TI - LC-MS-based metabolomics in the clinical laboratory. AB - The analysis of metabolites in human body fluids remains a challenge because of their chemical diversity and dynamic concentration range. Liquid chromatography (LC) in combination with tandem mass spectrometry (MS/MS) offers a robust, reliable, and economical methodology for quantitative single metabolite analysis and profiling of complete metabolite classes of a biological specimen over a broad dynamic concentration range. The application of LC-MS/MS based metabolomic approaches in clinical applications aims at both, the improvement of diagnostic sensitivity and specificity by profiling a metabolite class instead of a single metabolite analysis, and the identification of new disease specific biomarkers. In the present paper we discuss recent advances in method development for LC MS/MS analysis of lipids, carbohydrates, amino acids and biogenic amines, vitamins and organic acids with focus on human body fluids. In this context an overview on recent LC-MS/MS based metabolome studies for cancer, diabetes and coronary heart disease is presented. PMID- 22074958 TI - Chlorpromazine quantification in human plasma by UPLC-electrospray ionization tandem mass spectrometry. Application to a comparative pharmacokinetic study. AB - In the present study a method to quantify chlorpromazine in human plasma using cyclobenzaprine as the internal standard (IS) is described. The analyte and the IS were extracted from human plasma by a liquid-liquid extraction with diethyl ether/dichloromethane (70/30, v/v) and analyzed by an ultra performance liquid chromatography (UPLC) coupled to an electrospray tandem triple quadrupole mass spectrometer in positive mode (UPLC-ES(+)-MS/MS). Chromatography was performed isocratically on an Aquity UPLC BEH C18 1.7 MUm (50 mm * 2.1 mm i.d.) operating at 40 degrees C. The mobile phase was a mixture of 65% water+1% formic acid and 35% of acetonitrile at a flow-rate of 0.5 mL/min. The lowest concentration quantified was 0.5 ng/mL and a linear calibration curve over the range 0.5-200 ng/mL was obtained, showing intra-assay precisions from 2.4 to 5.8%, and inter assay precisions from 3.6 to 9.9%. The intra-assay accuracies ranged from 96.9 to 102.5%, while the inter-assay accuracies ranged from 94.1 to 100.3%. This analytical method was applied in a relative bioavailability study in order to compare a test chlorpromazine 100 mg simple dose formulation versus a reference in 57 volunteers of both sexes. The study was conducted in an open randomized two period crossover design and with a fourteen days washout period. Plasma samples were obtained over a 144-h interval. Since the 90% CI for both C(max), AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration and ANVISA, it was concluded that chlorpromazine 100 mg/dose was bioequivalent to the reference formulation, according to both the rate and extent of absorption. PMID- 22074959 TI - Bipolar temperaments and light. AB - BACKGROUND: Converging lines of evidence have established a relationship between exposure to ambient light and both mood state and mood disorders. In view of the association between mood disorder and affective disposition, in this study, the relationship between temperament (depressive, cyclothymic, hyperthymic, irritable and anxious) and daily light exposure was closely examined. METHODS: Fifty-six subjects completed the Japanese standardized version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire version (TEMPS-A) and illuminance of daytime using actigraphy. RESULTS: Cyclothymic temperament scores were significantly and negatively associated with illuminance of daytime whereas hyperthymic temperament scores were significantly and positively associated with illuminance of daytime. LIMITATIONS: Sample size was relatively small and they were only healthy subjects and no patients. CONCLUSIONS: The findings suggest that illuminance of daytime may be related to both cyclothymic and hyperthymic temperaments but that the associations lie in opposite directions. If this is the case, it seems important to consider individual patients' temperaments when light therapy is used to treat their depressive episode. Further studies are required to determine why and how these temperaments are associated with illuminance. PMID- 22074960 TI - A simple synthesis of APM ([p-(N-acrylamino)-phenyl]mercuric chloride), a useful tool for the analysis of thiolated biomolecules. AB - This study describes two novel synthetic procedures to prepare APM, a useful tool for the analysis and the purification of thiolated biomolecules. The methods developed are technically simple and robust and allowed the first full characterization of pure APM. Moreover, the efficacy of APM, as a biochemical tool, was demonstrated by analysis of tRNA thiolation by APM-PAGE. PMID- 22074961 TI - The synthesis of 2-nitroaryl-1,2,3,4-tetrahydroisoquinolines, nitro-substituted 5,6-dihydrobenzimidazo[2,1-a]isoquinoline N-oxides and related heterocycles as potential bioreducible substrates for the enzymes NAD(P)H: quinone oxidoreductase 1 and E. coli nitroreductase. AB - A series of 2-nitroaryl-1,2,3,4-tetrahydroisoquinolines 10 and nitro-substituted 5,6-dihydrobenzimidazo[2,1-a]isoquinoline N-oxides 11 have been synthesised and evaluated as potential bioreducible substrates for the enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1) and Escherichia coli nitroreductase (NR). Also prepared and evaluated were 2-(3,5-dinitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline 12 and 5,6-dihydro-10-nitropyrido[3",2":4',5']imidazo[2',1'-a]isoquinoline 12-oxide 13. Both compounds 10b and 13 were reduced faster by human NQO1 than by CB-1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]. PMID- 22074962 TI - Drugs as instruments: a new framework for non-addictive psychoactive drug use. AB - Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a "necessary" prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of "drug instrumentalization." Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific "instrumentalization goals" and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future. PMID- 22074963 TI - Toward an evolutionary basis for resilience to drug addiction. AB - According to Muller & Schumann (M&S), people would have evolved adaptations for learning to use psychoactive plants and drugs as instruments that reveal particularly advantageous in modern urban environments. Here I "instrumentalize" this framework to propose an evolutionary basis for the existence of a biological resilience to drug addiction in people. PMID- 22074964 TI - Drugs' rapid payoffs distort evaluation of their instrumental uses. AB - Science has needed a dispassionate valuation of psychoactive drugs, but a motivational analysis should be conducted with respect to long-term reward rather than reproductive fitness. Because of hyperbolic overvaluation of short-term rewards, an individual's valuation depends on the time she forms it and the times she will revisit it, sometimes making her best long-term interest lie in total abstinence. PMID- 22074965 TI - Drugs as instruments from a developmental child and adolescent psychiatric perspective. AB - Developmental, epidemiological, and neurobiological studies indicate that the adaptive and maladaptive functions, as well as immediate and long-term consequences of drug use, may vary by age. Early initiation seems to be associated with a reduced ability to use drugs purposely in a temporally stable, non-addictive manner. Prevention strategies should consider social environmental factors and aim to delay age at initiation. PMID- 22074966 TI - Drug use as consumer behavior. AB - Seeking integration of drug consumption research by a theory of memory function and emphasizing drug consumption rather than addiction, Muller & Schumann (M&S) treat drug self-administration as part of a general pattern of consumption. This insight is located within a more comprehensive framework for understanding drug use as consumer behavior that explicates the reinforcement contingencies associated with modes of drug consumption. PMID- 22074967 TI - Nonaddictive instrumental drug use: Theoretical strengths and weaknesses. AB - The potential to instrumentalize drug use based upon the detection of very many different drug states undoubtedly exists, and such states may play a role in psychiatric and many other drug uses. Nevertheless, nonaddictive drug use is potentially more parsimoniously explained in terms of sensation seeking/impulsivity and drug expectations. Cultural factors also play a major role in nonaddictive drug use. PMID- 22074968 TI - Non-addictive psychoactive drug use: Implications for behavioral addiction. AB - The newly proposed framework for non-addictive psychoactive substances postulated by Muller & Schumann (M&S) provides an interesting and plausible explanation for non-addictive drug use. However, with specific reference to the relevant behavioral addiction literature, this commentary argues that the model may unexpectedly hold utility not only for non-addictive use of drugs, but also for non-addictive use of other potentially addictive behaviors. PMID- 22074969 TI - Does drug mis-instrumentalization lead to drug abuse? AB - Understanding the perceived benefits of using drugs to achieve specific mental states will provide novel insights into the reasons individuals seek to use drugs. However, the precision of attempts to instrumentalize drugs is unclear both across drugs and individuals. Moreover, mis-instrumentalization, defined as discrepancies between such endpoints, may have relevance to understanding the relation among use, abuse, and addiction. PMID- 22074970 TI - Drug instrumentalization and evolution: Going even further. AB - Muller & Schumann (M&S) deserve applause for their interdisciplinary examination of drug use, evolution, and learning. Further steps can deepen their evolutionary analysis: a focus on adaptive benefits, a distinction between approach and consummatory behaviors, an examination of how drugs can create adaptive lag through changing human niche construction, the importance of other neurobehavioral mechanisms in drug use besides instrumentalization, and the importance of sociocultural dynamics and neural plasticity in both human evolution and drug use. PMID- 22074971 TI - Optimal drug use and rational drug policy. AB - The Muller & Schumann (M&S) view of drug use is courageous and compelling, with radical implications for drug policy and research. It implies that most nations prohibit most drugs that could promote happiness, social capital, and economic growth; that most individuals underuse rather than overuse drugs; and that behavioral scientists could use drugs more effectively in generating hypotheses and collaborating empathically. PMID- 22074972 TI - Sacramental and spiritual use of hallucinogenic drugs. AB - Arguably, the religious use of hallucinogenic drugs stems from a human search of metaphysical insight rather than from a direct need for cognitive, emotional, social, physical, or sexual improvement. Therefore, the sacramental and spiritual intake of hallucinogenic drugs goes so far beyond other biopsychosocial functions that it deserves its own category in the drug instrumentalization list. PMID- 22074973 TI - The instrumental rationality of addiction. AB - The claim that non-addictive drug use is instrumental must be distinguished from the claim that its desired ends are evolutionarily adaptive or easy to comprehend. Use can be instrumental without being adaptive or comprehensible. This clarification, together with additional data, suggests that Muller & Schumann's (M&S's) instrumental framework may explain addictive, as well as non addictive consumption. PMID- 22074974 TI - Drug addiction finds its own niche. AB - The evolutionary framework suggested by Muller & Schumann (M&S) can be extended further by considering drug-taking in terms of Niche Construction Theory (NCT). It is suggested here that genetic and environmental components of addiction are modified by cultural acceptance of the advantages of non-addicted drug taking and the legitimate supply of performance-enhancing drugs. This may then reduce the prevalence of addiction. PMID- 22074975 TI - But is it evolution...? AB - We applaud Muller & Schumann (M&S) for bringing needed attention to the problem of motivation for common non-addictive drug use, as opposed to the usual focus on exotic drugs and addiction. Unfortunately, their target article has many underdeveloped and sometimes contradictory ideas. Here, we will focus on three key issues. PMID- 22074976 TI - Why do we take drugs? From the drug-reinforcement theory to a novel concept of drug instrumentalization. AB - The drug-reinforcement theory explains why humans get engaged in drug taking behavior. This theory posits that drugs of abuse serve as biological rewards by activating the reinforcement system. Although from a psychological and neurobiological perspective this theory is extremely helpful, it does not tell us about the drug-taking motives and motivation of an individual. The definition of drug instrumentalization goals will improve our understanding of individual drug taking profiles. PMID- 22074977 TI - Flaws of drug instrumentalization. AB - The adaptive use of drugs, or "drug instrumentalization," is presented as a reality that the scientific literature has largely ignored. In this commentary, we demonstrate why this concept has limited value from the standpoint of nosology, why it should not be viewed as "adaptive," and why it has dangerous implications for policy and public health efforts. PMID- 22074978 TI - Psychoactive drug use: Expand the scope of outcome assessment. AB - The "hijacking" and "drug instrumentalization" models of psychoactive drug use predict opposite outcomes in terms of adaptive behavior and fitness benefits. Which is the range of applicability of each model? To answer this question, we need more data than those reported by studies focusing on medical, psychiatric, and legal problems in addicted users. An evolutionary analysis requires a much wider focus. PMID- 22074979 TI - Drugs, mental instruments, and self-control. AB - The instrumental model offered by Muller & Schumann (M&S) is broadened to apply not only to drugs, but also to other methods of self-control, including the use of mental constructs to produce adaptive changes in behavior with the possibility of synergistic interactions between various instruments. PMID- 22074980 TI - Aspects of nicotine utilization. AB - This commentary reviews the effects of nicotine on mood and cognition in support of the drug utilization concept of Muller & Schumann (M&S). Specifically, it amplifies the concept with the nicotine utilization hypothesis (NUH), which opposes the nicotine withdrawal hypothesis (NWH). Evidence against NWH comes from changes in mood after abstinence and the performance effects of nicotine supporting drug utilization. PMID- 22074981 TI - Governing drug use through neurobiological subject construction: The sad loss of the sociocultural. AB - Based on their "drugs as instruments" framework, Muller & Schumann (M&S) propose a staged drug policy that matches well the neoliberal governance scheme. To mend the sad loss of the sociocultural dimension in their model, I propose three such considerations: first, sociocultural interactions with the brain; second, sociocultural context and justice of drug use; and third, sociocultural preparedness for implementing their drug policy. PMID- 22074982 TI - A strain of Saccharomyces cerevisiae evolved for fermentation of lignocellulosic biomass displays improved growth and fermentative ability in high solids concentrations and in the presence of inhibitory compounds. AB - BACKGROUND: Softwoods are the dominant source of lignocellulosic biomass in the northern hemisphere, and have been investigated worldwide as a renewable substrate for cellulosic ethanol production. One challenge to using softwoods, which is particularly acute with pine, is that the pretreatment process produces inhibitory compounds detrimental to the growth and metabolic activity of fermenting organisms. To overcome the challenge of bioconversion in the presence of inhibitory compounds, especially at high solids loading, a strain of Saccharomyces cerevisiae was subjected to evolutionary engineering and adaptation for fermentation of pretreated pine wood (Pinus taeda). RESULTS: An industrial strain of Saccharomyces, XR122N, was evolved using pretreated pine; the resulting daughter strain, AJP50, produced ethanol much more rapidly than its parent in fermentations of pretreated pine. Adaptation, by preculturing of the industrial yeast XR122N and the evolved strains in 7% dry weight per volume (w/v) pretreated pine solids prior to inoculation into higher solids concentrations, improved fermentation performance of all strains compared with direct inoculation into high solids. Growth comparisons between XR122N and AJP50 in model hydrolysate media containing inhibitory compounds found in pretreated biomass showed that AJP50 exited lag phase faster under all conditions tested. This was due, in part, to the ability of AJP50 to rapidly convert furfural and hydroxymethylfurfural to their less toxic alcohol derivatives, and to recover from reactive oxygen species damage more quickly than XR122N. Under industrially relevant conditions of 17.5% w/v pretreated pine solids loading, additional evolutionary engineering was required to decrease the pronounced lag phase. Using a combination of adaptation by inoculation first into a solids loading of 7% w/v for 24 hours, followed by a 10% v/v inoculum (approximately equivalent to 1 g/L dry cell weight) into 17.5% w/v solids, the final strain (AJP50) produced ethanol at more than 80% of the maximum theoretical yield after 72 hours of fermentation, and reached more than 90% of the maximum theoretical yield after 120 hours of fermentation. CONCLUSIONS: Our results show that fermentation of pretreated pine containing liquid and solids, including any inhibitory compounds generated during pretreatment, is possible at higher solids loadings than those previously reported in the literature. Using our evolved strain, efficient fermentation with reduced inoculum sizes and shortened process times was possible, thereby improving the overall economic viability of a woody biomass-to-ethanol conversion process. PMID- 22074983 TI - Exact two-stage designs for phase II activity trials with rank-based endpoints. AB - Features common to phase II clinical trials include limited knowledge of the experimental treatment being evaluated, design components reflecting ethical considerations, and small to moderate sample sizes as a result of resource constraints. It is for these reasons that there exist many two-stage designs proposed in the literature for use in this context. The majority of these designs are for binary endpoints and based on exact probability calculations, or are for continuous endpoints and rooted in asymptotic approximations to the null distribution. We present exact two-stage Mann-Whitney designs in the context of two-arm randomized clinical trials. In addition to describing the designs, we present tables of decision rules under a variety of assumed realities for use in trial planning. PMID- 22074984 TI - A novel caryophyllene type sesquiterpene lactone from Asparagus falcatus (Linn.); structure elucidation and anti-angiogenic activity on HUVECs. AB - In this study the novel caryophyllene type sesquiterpene lactone (aspfalcolide) has been isolated from the leaves of Asparagus falcatus (Linn.) and characterized by IR, 1D NMR, 2D NMR, EI-MS, HR-ESI-MS and X-ray single crystal diffraction analysis. The aspfalcolide crystallizes in the orthorhombic space group P2(1)2(1)2(1) with a = 6.37360(10), b = 7.6890(2), c = 27.3281(6) A, alpha = beta = gamma = 90( degrees ) and Z = 4. One intermolecular O-H?O hydrogen bond enforces these natural molecules to form infinite chains through the crystal. Aspfalcolide was screened for its anti-angiogenic activity in human umbilical vein endothelial cells (HUVECs) and the result showed the remarkable inhibitory effect of aspfalcolide on the proliferation (IC(50) 1.82 MUM), migration and tube formation of HUVECs. PMID- 22074985 TI - 3,5-Disubstituted-thiazolidine-2,4-dione analogs as anticancer agents: design, synthesis and biological characterization. AB - A series of 2,5-disubstituted-thiazolidine-2,4-dione analogs based on the newly identified lead 1, a potential anticancer agent via the inhibition of the Raf/MEK/extracellular signal regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/Akt signaling cascades, were synthesized and biologically characterized. A new lead structure, 15, was identified to have improved anti proliferative activities in U937 cells, to induce apoptosis in U937, M12 and DU145 cancer cells, and to arrest U937 cells at the S-phase. Furthermore, Western blot analysis demonstrated a correlation of the anti-proliferative activity and blockade of the Raf/MEK/ERK and PI3K/Akt signaling pathways. Collectively, these results strongly encourage further optimization of 15 as a new lead with multi target properties to develop more potent compounds as anticancer agents. PMID- 22074986 TI - 1,2,4-Triazole D-ribose derivatives: design, synthesis and antitumoral evaluation. AB - Herein we report the design, synthesis and characterization of novel 1,2,4 triazole d-ribose derivatives, as well as their synthetic precursors. The antitumoral activity against T cell lymphoma cell line of these products was studied. Structures containing a 1,2,4-triazolic ring linked by sulfur to the carbohydrate moiety showed a moderate antiproliferative activity. The presence of the second heterocyclic ring did not show significant changes in their biological activity. Meanwhile, structures with 3-thiobenzyl-5-substituted-1,2,4-triazole ring linked by nitrogen leads to compounds with a biphasic behavior, stimulating cell proliferation at low concentrations and inhibiting it at higher ones. An increment in the polarity was associated with a decrease in the activity of the evaluated compounds. A preliminary antitumoral screening pointed the 1,2,4 triazolic structures linked to protected sugars as promising leaders for further studies. PMID- 22074988 TI - Nanoparticle zeta -potentials. AB - For over half a century, alternating electric fields have been used to induce particle transport, furnishing the zeta-potential of analytes with sizes ranging from a few nanometers to several micrometers. Concurrent advances in nanotechnology have provided new materials for catalysis, self-assembly, and biomedical applications, all of which benefit from a thorough understanding of particle surface charge. Therefore, the measurement of the zeta-potential via electrophoretic light scattering (ELS) has become essential for nanoparticle (NP) research. However, the interpretation of NP electrophoretic mobility, especially that of ligand-coated NPs, can be a complex undertaking. Despite the inherent intricacy of these data, key concepts from colloidal science can help to distill valuable information from ELS. In this Account, we adopt PEGylated Au NPs as an illustrative example to explore extensions of the classical theories of Smoluchowski, Huckel, and Henry to more contemporary theories for ligand-coated NP systems such as those from Ohshima, and Hill, Saville, and Russel. First, we review the basic experimental considerations necessary to understand NP electrophoretic mobility, identifying when O'Brien and White's numerical solution of the standard electrokinetic model should be adopted over Henry's closed-form analytical approximation. Next, we explore recent developments in the theory of ligand-coated particle electrophoresis, and how one can furnish accurate and meaningful relationships between measured NP mobility, zeta-potential, and surface charge. By identifying key ligand-coated NP parameters (e.g., coating thickness, permeability, molecular mass, and hydrodynamic segment size), we present a systematic method for quantitatively interpreting NP electrophoretic mobility. In addition to reviewing theoretical foundations, we describe our recent results that examine how the unique surface curvature of NPs alters and controls their properties. These data provide guidelines that can expedite the rational design of NPs for advanced uses, such as heterogeneous catalysis and in vivo drug delivery. As a practical demonstration of these concepts, we apply the ligand-coated theory to a recently developed noncovalent PEGylated Au NP drug delivery system. Our analysis suggests that anion adsorption on the Au NP core may enhance the stability of these NP-drug conjugates in solution. In addition to providing useful nanochemistry insights, the information in this Account will be useful to biomedical and materials engineers, who use ELS and zeta-potentials for understanding NP dynamics. PMID- 22074987 TI - The thrombospondin repeat containing protein MIG-21 controls a left-right asymmetric Wnt signaling response in migrating C. elegans neuroblasts. AB - Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. Although several Wnt signal transduction mechanisms have been described in detail, it is still largely unknown how cells are specified to adopt such different Wnt signaling responses. Here, we have used the stereotypic migration of the C. elegans Q neuroblasts as a model to study how two initially equivalent cells are instructed to activate either beta-catenin dependent or independent Wnt signaling pathways to control the migration of their descendants along the anteroposterior axis. We find that the specification of this difference in Wnt signaling response is dependent on the thrombospondin repeat containing protein MIG-21, which acts together with the netrin receptor UNC-40/DCC to control an initial left-right asymmetric polarization of the Q neuroblasts. Furthermore, we show that the direction of this polarization determines the threshold for Wnt/beta-catenin signaling, with posterior polarization sensitizing for activation of this pathway. We conclude that MIG-21 and UNC-40 control the asymmetry in Wnt signaling response by restricting posterior polarization to one of the two Q neuroblasts. PMID- 22074989 TI - Growth and exopolysaccharide yield of Lactobacillus delbrueckii ssp. bulgaricus DSM 20081 in batch and continuous bioreactor experiments at constant pH. AB - Some Lactobacillus delbrueckii ssp. bulgaricus strains are able to synthesize exopolysaccharides (EPS) and are therefore highly important for the dairy industry as starter cultures. The aim of this study was to investigate the nutritional requirements for growth and EPS production of Lactobacillus delbrueckii ssp. bulgaricus DSM 20081. A medium was developed from a semi-defined medium (SDM) in which glucose was replaced by lactose and different combinations of supplements (nucleobases, vitamins, salts, sodium formate and orotic acid) were added. Constant pH batch fermentation with the modified medium resulted in an EPS yield of approximately 210 mg glucose equivalents per liter medium. This was a 10-fold increase over flask cultivation of this strain in SDM. Although not affecting cell growth, the mixture of salts enhanced the EPS synthesis. Whereas EPS production was approximately 12 mg/g dry biomass without salt supplementation, a significantly higher yield (approximately 20 mg/g dry biomass) was observed after adding the salt mixture. In continuous fermentation, a maximal EPS concentration was obtained at a dilution rate of 0.31/h (80 mg EPS/L), which corresponded to a specific EPS production of 49 mg/g dry biomass. PMID- 22074990 TI - Functional roles of a tetraloop/receptor interacting module in a cyclic di-GMP riboswitch. AB - Riboswitches are a class of structural RNAs that regulate transcription and translation through specific recognition of small molecules. Riboswitches are attractive not only as drug targets for novel antibiotics but also as modular tools for controlling gene expression. Sequence comparison of a class of riboswitches that sense cyclic di-GMP (type-I c-di-GMP riboswitches) revealed that this type of riboswitch frequently shows a GAAA loop/receptor interaction between P1 and P3 elements. In the crystal structures of a type-I c-di-GMP riboswitch from Vibrio cholerae (the Vc2 riboswitch), the GNRA loop/receptor interaction assembled P2 and P3 stems to organize a ligand-binding pocket. In this study, the functional importance of the GAAA loop-receptor interaction in the Vc2 riboswitch was examined. A series of variant Vc2 riboswitches with mutations in the GAAA loop/receptor interaction were assayed for their switching abilities. In mutants with mutations in the P2 GAAA loop, expression of the reporter gene was reduced to approximately 40% - 60% of that in the wild-type. However, mutants in which the P3 receptor motif was substituted with base pairs were as active as the wild-type. These results suggested that the GAAA loop/receptor interaction does not simply establish the RNA 3D structure but docking of P2 GAAA loop reduces the flexibility of the GAAA receptor motif in the P3 element. This mechanism was supported by a variant riboswitch bearing a theophylline aptamer module in P3 the structural rigidity of which could be modulated by the small molecule theophylline. PMID- 22074991 TI - Significance of reflux of contrast medium into the inferior vena cava on computerized tomographic pulmonary angiogram. AB - Reflux of contrast medium into the inferior vena cava (IVC) is often detected on computerized tomographic pulmonary angiogram. The potential clinical implications and associated diagnoses of this finding have not been established. We investigated the prevalence and significance of reflux of contrast medium into the IVC in a large cohort of patients evaluated for possible pulmonary embolism (PE) by computerized tomographic pulmonary angiography. We retrospectively reviewed 1,065 consecutive computerized tomographic pulmonary angiographic examinations performed from January 1, 2007 through January 7, 2008 for the presence of reflux. Degree of reflux into the IVC and hepatic veins was graded from 1 (none) to 6 (severe). Patients' charts were reviewed for diagnoses during the index hospitalization and for background diseases. These clinical data were correlated with the reflux grade. The final study included 967 computerized tomographic pulmonary angiographic scans of 367 men and 600 women (mean age 62 +/ 20 years, range 17 to 103). Almost 1/2 (480, 49.6%) had grade 1, 310 (32.1%) had grades 2 to 3, and 177 (18.3%) had grades 4 to 6. Multivariate logistic regression found that pulmonary hypertension, history of congestive heart failure, chronic atrial fibrillation, and acute PE were associated with extensive reflux (grades 4 to 6) with odds ratios (95% confidence intervals) of 5.4 (3.0 to 9.9, p <0.001), 3.7 (2.3 to 6.1, p <0.001), 2.3 (1.0 to 5.3, p = 0.044), and 1.8 (1.2 to 2.9, p = 0.011), respectively. Interobserver agreement between the 2 readers for reflux grading was good (kappa = 0.77). In conclusion, extensive reflux of contrast medium into the IVC detected on computerized tomographic pulmonary angiogram may serve as a pathophysiologic marker of right heart dysfunction, specifically pulmonary hypertension, congestive heart failure, chronic atrial fibrillation, or PE. PMID- 22074992 TI - Sudden death associated with danon disease in women. AB - Danon disease is an X-linked systemic disorder characterized by left ventricular hypertrophy, mental retardation, and skeletal myopathy affecting young men. Electrocardiogram usually displays a Wolff-Parkinson-White preexcitation pattern. Less has been reported about the phenotype in women, although later-onset cardiac symptoms have been described. The aim of this study was to expand the knowledge of the phenotype of Danon disease in women. We clinically followed and evaluated with echocardiography, cardiac magnetic resonance imaging (cMRI), and genetic testing a family affected by Danon disease in which 2 men and 6 women showed a severe arrhythmogenic phenotype. Affected family members carried a nucleotide substitution at position 294 in exon 3 (c.294 G -> A) that changed a tryptophan residue to a stop codon at position W98X in the lysosome-associated membrane protein 2 (LAMP2) gene. Four women died suddenly (1 aborted) at 37 to 54 years of age. Wolff-Parkinson-White pattern with atrioventricular block was detected in 2 of 6 women. Four had successful pregnancies without symptoms of heart failure. cMRI showed late gadolinium enhancement areas in a clinically healthy woman who was a mutation carrier. Two patients underwent heart transplantation; histology of explanted hearts demonstrated severe interstitial fibrosis, hypertrophic cardiomyocytes with cytoplasmic vacuoles, and myofibrillar disarray. In conclusion, LAMP2 mutation can cause a severe arrhythmogenic phenotype in women that includes a high risk of sudden death. cMRI may be useful in women harboring LAMP2 mutations to permit early detection of cardiac involvement and guide timely considerations of implantable cardioverter-defibrillator therapy. Heart transplantation should be considered at onset of heart failure symptoms owing to rapid progression of the disease. PMID- 22074993 TI - Sub-chronic dietary tryptophan depletion--an animal model of depression with improved face and good construct validity. AB - Sub-chronic tryptophan depletion (SCTD) is proposed as an animal model for depression. Aims were to test the hypothesis and optimise the time of SCTD induced depression-related behaviour and associated biochemical changes. Sprague Dawley rats were treated with a low tryptophan (TRP) containing diet for 0, 7 or 14 days. Peripheral and central neurochemical markers were measured. SCTD-induced depression-related behaviour was assessed by the forced swim test (FST). Model sensitivity to antidepressants was tested by concomitant treatment with paroxetine. SCTD-induced significant reductions in weight gain and measures of peripheral and central TRP. Corticosterone, aldosterone and kynurenine (K), increased whilst kynurenic acid (KA), an NMDA antagonist decreased. 5-HT(2) receptor binding Bmax was enhanced but was reversed by paroxetine. Corticosterone and aldosterone were significantly negatively-correlated to weight gain. SCTD increased floating time and reduced swimming time in the FST but were reversed by paroxetine. Aldosterone was increased at 7 and 14 days, whereas other changes maximised at 14 days. Aldosterone may be an early marker or causal link for depression development. Increased corticosterone and brain tissue 5-HT-receptor density may be correlates of depressive behaviour. Consequential increases in NMDA signalling through increased K/KA ratios suggest the model may be useful for testing novel antidepressants. PMID- 22074994 TI - Medication overuse headache: a silent pandemic. PMID- 22074995 TI - CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis. AB - Studies on the genetic forms of epilepsy, chronic pain, and migraine caused by mutations in ion channels have given crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological disorders. In this review we focus on the role of mutated CaV2.1 (i.e., P/Q-type) voltage-activated Ca2+ channels, and on the ultimate consequences that mutations causing familial hemiplegic migraine type-1 (FHM1) have in neurotransmitter release. Transgenic mice harboring the human pathogenic FHM1 mutation R192Q or S218L (KI) have been used as models to study neurotransmission at several central and peripheral synapses. FHM1 KI mice are a powerful tool to explore presynaptic regulation associated with expression of CaV2.1 channels. Mutated CaV2.1 channels activate at more hyperpolarizing potentials and lead to a gain-of-function in synaptic transmission. This gain-of-function might underlie alterations in the excitatory/ inhibitory balance of synaptic transmission, favoring a persistent state of hyperexcitability in cortical neurons that would increase the susceptibility for cortical spreading depression (CSD), a mechanism believed to initiate the attacks of migraine with aura. PMID- 22074996 TI - CD80 and CD86 polymorphisms in populations of various ancestries: 5 new CD80 promoter alleles. AB - CD80 and CD86 are closely linked genes on chromosome 3 that code for glycoproteins of the immunoglobulin superfamily, expressed on the surface of antigen-presenting cells. These costimulatory molecules play essential roles for stimulation and inhibition of T cells through binding to CD28 and CTLA-4 receptors. In this study, CD80 promoter and CD86 exon 8 polymorphisms were analyzed to investigate the genetic diversity and microevolution of the 2 genes. We genotyped 1,124 individuals, including Brazilians of predominantly European, mixed African and European, and Japanese ancestry, 5 Amerindian populations, and an African sample. All variants were observed in Africans, which suggests their origin in Africa before the human migrations out of that continent. Five new CD80 promoter alleles were identified and confirmed by cloning and sequencing, and promoter 2 is most likely the ancestral allele. Nucleotide -79 is monomorphic in 4 Amerindian populations, where the presence of the -79 G allele is probably the result of gene flow from non-Amerindians. PMID- 22074997 TI - Identification of HLA-A24-restricted CD8(+) cytotoxic T-cell epitopes derived from mammaglobin-A, a human breast cancer-associated antigen. AB - Human breast cancer-associated antigen, mammaglobin-A (Mam-A), potentially offers a novel therapeutic target as a breast cancer vaccine. In this study, we define the CD8(+) cytotoxic T lymphocyte (CTL) response to Mam-A-derived candidate epitopes presented in the context of HLA-A24 (A*2402). HLA-A24 has a frequency of 72% in Japanese, 27% in Asian Indian, and 18% in Caucasian populations. Using a human leukocyte antigen (HLA)-binding prediction algorithm we identified 7 HLA A24-restricted Mam-A-derived candidate epitopes (MAA24.1-7). Membrane stabilization studies with TAP-deficient T2 cells transfected with HLA-A2402 (T2.A24) indicated that MAA24.2 (CYAGSGCPL) and MAA24.4 (ETLSNVEVF) have the highest HLA-A24 binding affinity. Further, 2 CD8(+) CTL cell lines generated in vitro against T2.A24 cells individually loaded with Mam-A-derived candidate epitopes demonstrated significant cytotoxic activity against MAA24.2 and MAA24.4. In addition, the same CD8(+) CTL lines lysed the HLA-A24(+)/Mam-A(+) stable transfected human breast cancer cell lines AU565 and MDA-MB-361. However, these CTLs had no cytotoxicity against HLA-A24(-)/Mam-A(+) and HLA-A24(+)/Mam-A(-) breast cancer cell lines. In summary, our results define HLA-A24-restricted, Mam A-derived, CD8(+) CTL epitopes that can potentially be employed for Mam-A-based breast cancer vaccine therapy to breast cancer patients with HLA-A24 phenotype. PMID- 22074998 TI - HLA-DRB1 allele frequencies and C4 copy number variation in Finnish sarcoidosis patients and associations with disease prognosis. AB - Sarcoidosis is a multiorgan immune-mediated disease of unknown etiology with varying clinical pictures. We studied 3 genes in the major histocompatibility complex region (HLA-DRB1 and complement C4A and C4B) in patients with resolved disease after a 2-year follow-up (n = 90) and in patients whose disease was still active at that time point (n = 98) and compared them with controls (n = 150). Our primary aim was to detect genetic differences between the patient groups. We observed that the susceptibility allele for sarcoidosis was HLA-DRB1*15:01 (p = 0.011; odds ratio [OR] = 1.67) and the protective allele was HLA-DRB1*01:01 (p = 0.001; OR = 0.43). HLA-DRB1*03:01 was associated with resolving disease when compared with the persistent group (p = 0.011; OR = 2.22). The probability of having resolving disease was even greater if the patient had HLA-DRB1*03:01 and did not have extrapulmonary lesions (p = 0.001; OR = 3.39). By evaluating amino acid variants of the HLA-DRB1 gene, we determined that specific amino acids in pockets 4, 7, and 9 were associated with the prognosis of sarcoidosis. Our results support the importance of HLA-DRB1 as a predisposing gene for sarcoidosis. Particularly, HLA-DRB1*03:01 and polymorphisms of DRB1 pocket residues were associated with a favorable prognosis. Thus, accurate categorization of disease phenotype and HLA-DRB1 sequencing offer a basis for disease course estimation of sarcoidosis. PMID- 22075000 TI - School-aged children who were exposed to sodium valproate in utero have impaired language scores when compared with a population mean score. PMID- 22074999 TI - Human leukocyte antigen class I (A, B, C) and II (DRB1) diversity in the black and Caucasian South African population. AB - A cross-section of black and Caucasian South Africans (N = 302) were genotyped at high resolution (class I HLA-A, -B, -C and class II HLA-DRB1). Five new class I alleles (A*30:01:02, A*30:02:02, A*68:27, B*42:06, and B*45:07) and one new confirmatory allele (A*29:11) were identified in the black population. Alleles and haplotypes showed expected differences between the black and Caucasian populations, with the black population, on average, showing a broader spectrum of allele representation (less single allele dominance). The most prevalent alleles at the four loci in the black population were A*30:01, B*58:02, C*06:02, and DRB1*13:01 and in the Caucasian population were A*02:01:01, B*07:02:01, C*07:01, and DRB1*03:01. HLA-B, and HLA-C loci showed the strongest overall linkage disequilibrium (LD) and HLA-B/HLA-C two locus haplotypes also showed the strongest LD (D'(ij)) in both population groups. Bw allotype representation was similar between the two populations; however C allotypes differed significantly (C1 higher representation in Caucasians; C2 higher representation in blacks). HLA A Supertype family phenotypic frequencies did not differ between the two populations, but four (B08, B27, B58, and B62) HLA-B Supertype families differed significantly. However, vaccine coverage estimation came close to 100% in both population groups, with inclusion of only four Supertype families (A1, A2, B7, B58). PMID- 22075001 TI - Patients Association deems hospitals' care of older patients "unacceptable". PMID- 22075002 TI - Rap1 binds single-stranded DNA at telomeric double- and single-stranded junctions and competes with Cdc13 protein. AB - The ends of eukaryotic chromosomes are protected by specialized telomere chromatin structures. Rap1 and Cdc13 are essential for the formation of functional telomere chromatin in budding yeast by binding to the double-stranded part and the single-stranded 3' overhang, respectively. We analyzed the binding properties of Saccharomyces castellii Rap1 and Cdc13 to partially single-stranded oligonucleotides, mimicking the junction of the double- and single-stranded DNA (ds-ss junction) at telomeres. We determined the optimal and the minimal DNA setup for a simultaneous binding of Rap1 and Cdc13 at the ds-ss junction. Remarkably, Rap1 is able to bind to a partially single-stranded binding site spanning the ds-ss junction. The binding over the ds-ss junction is anchored in a single double-stranded hemi-site and is stabilized by a sequence-independent interaction of Rap1 with the single-stranded 3' overhang. Thus, Rap1 is able to switch between a sequence-specific and a nonspecific binding mode of one hemi site. At a ds-ss junction configuration where the two binding sites partially overlap, Rap1 and Cdc13 are competing for the binding. These results shed light on the end protection mechanisms and suggest that Rap1 and Cdc13 act together to ensure the protection of both the 3' and the 5' DNA ends at telomeres. PMID- 22075004 TI - Reduced time for urinary alkalinization before high-dose methotrexate with preadmission oral bicarbonate. AB - PURPOSE: Hydration and urinary alkalinization are essential for reducing renal dysfunction with high dose methotrexate (HDMTX). This report presents an analysis of institutional methods used to achieve adequate urinary alkalinization and output for patients receiving single agent HDMTX. Renal and metabolic parameters of tolerance were examined. METHODS: Medical records of adult patients receiving HDMTX during the calendar years of 2008-2009 were retrospectively reviewed to determine the time to achieve urine pH > 7. Number of hospital days, bicarbonate dose, ordered hydration rate, urine output, and urine pH were assessed. A survival analysis model was run for time to urine pH > 7 using preadmission oral bicarbonate as a predictor variable and including a frailty term. Observational statistics were performed for other parameters. RESULTS: The analysis included 79 encounters for ten patients. Urine pH > 7 was achieved more rapidly in patients receiving preadmission oral bicarbonate (P = 0.012). The number of patients receiving HDMTX on the same day as admission was greater for those receiving preadmission oral bicarbonate (47%) in comparison to those who did not (2%), and they spent less time in the hospital. A standard regimen for hydration and urinary alkalinization based on this project is reported. The nature and frequency of adverse events were as expected for this treatment. CONCLUSION: At our institution, the time to achieve urinary alkalinization was reduced for patients receiving preadmission oral bicarbonate which facilitated chemotherapy infusion on the same day as admission and decreased the number of calendar days that patients stayed in the hospital. PMID- 22075003 TI - Connexin 39.9 protein is necessary for coordinated activation of slow-twitch muscle and normal behavior in zebrafish. AB - In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for myogenesis. Although gap junctions were once believed to be absent from differentiated skeletal muscle in mammals, recent studies in teleosts revealed that differentiated muscle does express connexins and is electrically coupled, at least at the larval stage. These findings raised questions regarding the functional significance of gap junctions in differentiated muscle. Our analysis of gap junctions in muscle began with the isolation of a zebrafish motor mutant that displayed weak coiling at day 1 of development, a behavior known to be driven by slow-twitch muscle (slow muscle). We identified a missense mutation in the gene encoding Connexin 39.9. In situ hybridization found connexin 39.9 to be expressed by slow muscle. Paired muscle recordings uncovered that wild-type slow muscles are electrically coupled, whereas mutant slow muscles are not. The further examination of cellular activity revealed aberrant, arrhythmic touch-evoked Ca(2+) transients in mutant slow muscle and a reduction in the number of muscle fibers contracting in response to touch in mutants. These results indicate that Connexin 39.9 facilitates the spreading of neuronal inputs, which is irregular during motor development, beyond the muscle cells and that gap junctions play an essential role in the efficient recruitment of slow muscle fibers. PMID- 22075006 TI - Loading profile of topotecan into polyvinyl alcohol microspheres (DC BeadTM) over a 7-day period. AB - PURPOSE: DC BeadTM is successfully used for chemoembolization of various liver cancers. The purpose of this study was to determine the loading capacity of the semi-synthetic topoisomerase-1 inhibitor topotecan into the DC BeadTM microspheres under static or agitated conditions and to assess the physicochemical stability over a period of 7 days. METHODS: Commercially available topotecan hydrochloride powder (Hycamtin(r)) was reconstituted with water for injection to yield a nominal concentration of 1 mg/mL topotecan. Polyvinyl alcohol (PVA)-based microspheres (DC BeadTM, 300-500 um, 2 mL/vial) were mixed with 4 mL of the reconstituted topotecan solution. Vials were stored light protected at room temperature under static or agitated conditions for 7 days (n = 3, for each loading condition). At different time intervals, samples were taken from the excess solution and assayed via a stability-indicating HPLC assay. Drug-loading profiles were determined by measuring the remaining topotecan concentration in the excess solution. RESULTS: Under agitated conditions, topotecan was loaded into the microspheres rapidly after mixing. After 5 min 86.4 +/- 0.1% of topotecan was loaded. Under static conditions, drug uptake was slower. Only 65.0 +/- 0% were loaded after 5 min; 86.6 +/- 0.1% drug uptake was achieved not until 1 h. Over a storage period of 7 days, topotecan remained loaded in the DC BeadTM microspheres at a level of >90%. CONCLUSION: Drug uptake of 4 mg topotecan (1 mg/mL solution) into DC BeadsTM was faster under agitated loading conditions. Nevertheless, after 1 h, ~90% of topotecan was loaded into the DC BeadTM microspheres independent from the type of loading condition. The loading rate remained >90% over the observation period of 7 days and light protected storage at room temperature. Loading and stability of topotecan-loaded DC BeadsTM is suitable and convenient for preparation in a pharmacy-based cytotoxic preparation unit. PMID- 22075005 TI - Long-term stability study of clofarabine injection concentrate and diluted clofarabine infusion solutions. AB - PURPOSE: The aim of this study was to investigate the physicochemical stability of clofarabine (CAFdA) injection concentrate and ready-to-use CAFdA infusion solutions over a prolonged period of 28 days. METHODS: To determine the stability of CAFdA infusion solutions, the injection concentrate (Evoltra(r), 1 mg/mL, Genzyme) was diluted either with 0.9% sodium chloride or 5% glucose infusion solution. The resulting concentrations of 0.2 mg/mL or 0.6 mg/mL, respectively, were chosen to represent the lower and upper limit of the ordinary concentration range. Test solutions were stored under refrigeration (2-8 degrees C) or at room temperature either light protected or exposed to light. CAFdA concentrations and pH values were determined at different time intervals throughout a 28-day storage period. Compatibility of diluted CAFdA infusion solutions (0.1-0.4 mg/mL) with different container materials (polyvinyl chloride (PVC), glass, and polypropylene/polyethylene (PP/PE)) was tested over a 48-h storage period. CAFdA concentrations were measured by a stability-indicating reversed phase high performance liquid chromatography (HPLC) assay with ultraviolet detection. RESULTS: CAFdA injection concentrate and CAFdA infusion solutions remained physicochemically stable (>90% CAFdA) for 4 weeks. Results are independent of storage conditions, drug concentrations (0.2, 0.6, and 1.0 mg/mL) and diluents (0.9% sodium chloride, 5% glucose infusion solution). Adsorption of CAFdA to container material can be excluded. CONCLUSIONS: CAFdA injection concentrate and diluted infusion solutions in commonly used vehicles are stable for at least 28 days either refrigerated or at room temperature. Physicochemical stability favors pharmacy-based centralized preparation. Due to microbiological reasons, strict aseptic handling and storage of the products under refrigeration is recommended. PMID- 22075007 TI - Obstructive sleep apnoea; a rare cause of pseudophaeochromocytoma. PMID- 22075008 TI - Acute shrinkage of a giant prolactinoma, masquerading as an erosive skull base tumour, with cabergoline. PMID- 22075009 TI - Acute chest pain of cardiovascular aetiology: a diagnostic dilemma. PMID- 22075011 TI - Knuckle-dimple sign. PMID- 22075012 TI - Advance care planning and the older patient. AB - Making treatment decisions for older people is difficult, because of the complex interplay of their multiple co-morbidities, but also because of the fine balance of risks vs. benefit in any chosen management plan. This becomes even more difficult when they lose the capacity to tell us what they want, and often in such situations we have to rely on information from others in order to make decisions based on their best interests. Advance care planning should help with making these decisions clearer, based on the documented preferences of what the patient would have wanted while capacity was still present. However, such documents are still very rarely used, and even if they are, health-care professionals are often wary of them for the multitude of ethical and legal problems that can arise. PMID- 22075013 TI - Racial and ethnic disparities in neuraxial labor analgesia. AB - BACKGROUND: Racial and ethnic disparities in the treatment of pain have been well documented, and there is evidence of such disparities in neuraxial analgesia use. Our objectives of this study were to analyze racial/ethnic disparities in neuraxial analgesia use, as well as anticipated use, among laboring Hispanic, African-American, and Caucasian women, and to evaluate sociodemographic, clinical, and decision-making predictors of actual and anticipated neuraxial analgesia use among these women. METHODS: Laboring women, in a large urban academic hospital, were interviewed using a face-to-face survey to determine individual factors that may influence choice of labor analgesia. After delivery, the type of labor analgesia used was recorded. The primary outcome was use of neuraxial analgesia. Multivariable logistic regression models were estimated to test the likelihood that race and ethnicity were significantly associated with neuraxial analgesia use, anticipated neuraxial analgesia use, and the intrapartum decision to use neuraxial analgesia. RESULTS: There was a univariate association between race/ethnicity and anticipated as well as actual use of neuraxial analgesia. However, there was no association between race/ethnicity and the intrapartum decision to use neuraxial analgesia. After controlling for confounders, the association between race/ethnicity and actual use of neuraxial analgesia no longer remained significant (adjusted odds ratio: Hispanic versus Caucasian women 0.66, 95% confidence interval [CI]: 0.24 to 1.80; African American versus Caucasian women 0.93, 95% CI: 0.31 to 2.77). In contrast, Hispanic women were less likely than Caucasian women to anticipate using neuraxial analgesia even after controlling for confounders (adjusted odds ratio 0.40, 95% CI: 0.20 to 0.82). CONCLUSIONS: After controlling for confounding variables, Hispanic women anticipated using neuraxial analgesia at a lower rate than other racial/ethnic groups; however, actual use was similar among groups. PMID- 22075014 TI - Echo rounds: aneurysm of the anterior mitral valve. PMID- 22075015 TI - Aortic intramural hematoma: echocardiographic characteristics. PMID- 22075016 TI - Tracheal intubation through the I-gelTM supraglottic airway versus the LMA FastrachTM: a randomized controlled trial. AB - BACKGROUND: The i-gelTM is a supraglottic airway device not requiring inflation of a cuff for lung ventilation. Its design allows for unobstructed passage of a tracheal tube and previous studies have demonstrated a favorable alignment with the glottic inlet. In this prospective randomized study, we compared the success rate of blind tracheal intubation using the i-gel and the laryngeal mask airway (LMA) FastrachTM. METHODS: One hundred sixty patients requiring general anesthesia and airway management were randomized to tracheal intubation using the i-gel or the LMA Fastrach. After induction of general anesthesia, the allocated device was inserted and adequate lung ventilation was confirmed. Blind tracheal intubation was then attempted. First attempt and overall tracheal intubation success rates were evaluated and tracheal intubation times were measured. RESULTS: Eighty patients were recruited in each study group. Successful tracheal intubation was obtained on the first attempt in 69% of patients with the i-gel and 74% of patients with the LMA Fastrach (95% confidence interval [CI] of difference, -9% to 19%, P = 0.60). The overall intubation success rate was lower using the i-gel than it was using the LMA Fastrach (73% vs 91%, 95% CI of difference, 7% to 31%, P < 0.0001). CONCLUSIONS: On first attempts, successful blind tracheal intubation was obtained at comparable rates using the i-gel and the LMA Fastrach. However, when the first attempt was unsuccessful, subsequent attempts through the i-gel did not significantly increase tracheal intubation success rate. The LMA Fastrach yielded a higher overall intubation success rate. PMID- 22075017 TI - The relationship between preoperative and primary care blood pressure among veterans presenting from home for surgery: is there evidence for anesthesiologist initiated blood pressure referral? AB - BACKGROUND: American College of Cardiology/American Heart Association guidelines describe the perioperative evaluation as "a unique opportunity to identify patients with hypertension"; however, factors such as anticipatory stress or medication noncompliance may induce a bias toward higher blood pressure, leaving clinicians unsure about how to interpret preoperative hypertension. Information describing the relationship between preoperative intake blood pressure and primary care measurements could help anesthesiologists make primary care referrals for improved blood pressure control in an evidence-based fashion. We hypothesized that the preoperative examination provides a useful basis for initiating primary care blood pressure referral. METHODS: We analyzed retrospective data on 2807 patients who arrived from home for surgery and who were subsequently evaluated within 6 months after surgery in the primary care center of the same institution. After descriptive analysis, we conducted multiple linear regression analysis to identify day-of-surgery (DOS) factors associated with subsequent primary care blood pressure. We calculated the sensitivity, specificity, and positive and negative predictive value of different blood pressure referral thresholds using both a single-measurement and a 2-stage screen incorporating recent preoperative and DOS measurements for identifying patients with subsequently elevated primary care blood pressure. RESULTS: DOS systolic blood pressure (SBP) was higher than subsequent primary care SBP by a mean bias of 5.5 mm Hg (95% limits of agreement + 43.8 to -32.8). DOS diastolic blood pressure (DBP) was higher than subsequent primary care DBP by a mean bias of 1.5 mm Hg (95% limits of agreement +13.0 to -10.0). Linear regression of DOS factors explained 19% of the variability in primary care SBP and 29% of the variability in DBP. Accounting for the observed bias, a 2-stage SBP referral screen requiring preoperative clinic SBP >=140 mm Hg and DOS SBP >=146 mm Hg had 95.9% estimated specificity (95% confidence interval [CI] 94.4 to 97.0) for identifying subsequent primary care SBP >=140 mm Hg and estimated sensitivity of 26.8% (95% CI 22.0 to 32.0). A similarly high specificity using a single DOS SBP required a threshold SBP >=160 mm Hg, for which estimated specificity was 95.2% (95% CI 94.2 to 96.1). For DBP, a presenting DOS DBP >=92 mm Hg had 95.7% specificity (95% CI 94.8 to 96.4) for subsequent primary care DBP >=90 mm Hg with a sensitivity of 18.8% (95% CI 14.4 to 24.0). CONCLUSION: A small bias toward higher DOS blood pressures relative to subsequent primary care measurements was observed. DOS factors predicted only a small proportion of the observed variation. Accounting for the observed bias, a 2-stage SBP threshold and a single-reading DBP threshold were highly specific though insensitive for identifying subsequent primary care blood pressure elevation. PMID- 22075018 TI - Continuous epicapsular ropivacaine 0.3% infusion after minimally invasive hip arthroplasty: a prospective, randomized, double-blinded, placebo-controlled study comparing continuous wound infusion with morphine patient-controlled analgesia. AB - BACKGROUND: In this study, we investigated the impact of a continuous wound infusion with ropivacaine 0.3% on pain and morphine consumption after minimally invasive hip arthroplasty. METHODS: Seventy-six consecutive patients scheduled for elective minimally invasive hip replacement using spinal anesthesia were prospectively included in this double-blind study. Epicapsular placement of a 15 cm fenestrated catheter was performed by the surgeon. Patients were randomized to receive either 20 mL ropivacaine 0.3% (R-group) or 20 mL NaCl 0.9% (P-group) applied into the wound as a bolus before wound closure. A continuous infusion of either ropivacaine 0.3% or placebo was then infused at 8 mL/h for 48 hours after surgery with an elastomeric pump. Morphine IV-patient-controlled analgesia was offered to all patients. Morphine consumption, pain at rest and with motion, and total and unbound ropivacaine plasma concentration were recorded during the 48 hour study period. Postoperative follow-up was performed at 3 months. RESULTS: Demographic and surgical data were similar in both groups. Mean morphine consumption was significantly lower in the R-group than in the P-group during the first 48 postoperative hours: 45.4 +/- 9.5 vs 69.7 +/- 9.6 (P < 0.0001). There was a mean reduction of 14.4 mg for the first 24 postoperative hours (95% confidence interval [CI] 12.6 to 16.1) and 20.8 mg for the next 24 hours (95% CI 19.1 to 22.4). Pain scores at rest and with motion were lower in the R-group (P < 0.0001). Mean patient satisfaction increased 22.7% from baseline (CI 95% 15.9 to 29.6) in the R-group. Total and unbound ropivacaine plasma concentrations were below toxic levels in the R-group. The free ropivacaine concentration was 0.14 and 0.11 MUgmol/L at T(24) and T(48), respectively, in the R-group. At 3 months postoperatively, hip pain and analgesic consumption were similar, but a significant reduction in wound discomfort to touch (31.2; 95% CI 27.7 to 34.7) and pressure (24; 95% CI 20.1 to 27.9) was observed in the R-group (P < 0.0001). CONCLUSIONS: Continuous epicapsular wound infusion with ropivacaine 0.3% after minimally invasive hip replacement is an efficient technique for reducing morphine consumption and improving the quality of postoperative analgesia. The beneficial effects of this technique are still present 3 months after surgery. PMID- 22075019 TI - Spinal cord ischemia occurring in association with induced hypotension for colonic surgery. AB - A 19-year-old woman underwent an ileoanal pull-through. Intraoperatively, deepening of anesthesia was associated with reduced bleeding. Therefore, induced hypotension, mean arterial blood pressure 50 to 55 mm Hg, was maintained for 2.5 hours. Postoperatively, the patient was paraplegic with spinal cord infarction on magnetic resonance imaging from T9 to the tip of the conus medullaris. The collateralization of the anterior spinal artery is very variable and it seems likely that in this individual induced hypotension was associated with inadequate blood flow in the distribution of the artery of Adamkiewicz. PMID- 22075020 TI - The effects of isoflurane and desflurane on cognitive function in humans. AB - BACKGROUND: The etiology of postoperative cognitive decline (POCD) remains to be determined. Anesthetic isoflurane, but not desflurane, may induce neurotoxicity. However, the functional consequences of these effects have not been assessed. We therefore performed a pilot study to determine the effects of isoflurane and desflurane on cognitive function in humans. METHODS: The subjects included patients who had lower extremity or abdominal surgery under spinal anesthesia alone (S, n = 15), spinal plus desflurane anesthesia (SD, n = 15), or spinal plus isoflurane anesthesia (SI, n = 15) by randomization. Each of the subjects received cognitive tests immediately before and 1 week after anesthesia and surgery administered by an investigator who was blinded to the anesthesia regimen. POCD was defined using the scores from each of these tests. RESULTS: We studied 45 subjects, 24 males and 21 females. The mean age of the subjects was 69.0 +/- 1.9 years. There was no significant difference in age and other characteristics among the treatment arms. The mean number of cognitive function declines in the S, SD, and SI groups was 1.13, 1.07, and 1.40, respectively. POCD incidence after SI (27%), but not SD (0%), anesthesia was higher than that after S (0%), P = 0.028 (3-way comparison). CONCLUSION: These findings from our pilot study suggest that isoflurane and desflurane may have different effects on postoperative cognitive function, and additional studies with a larger sample size and longer times of follow-up testing are needed. PMID- 22075022 TI - Identification of seven Xanthomonas oryzae pv. oryzicola genes potentially involved in pathogenesis in rice. AB - Xanthomonas oryzae pv. oryzicola (Xoc) causes bacterial leaf streak (BLS) in rice, an emerging and destructive disease worldwide. Identification of key virulence factors is a prerequisite for understanding the pathogenesis of Xoc. In this study, a Tn5-tagged mutant library of Xoc strain RS105 was screened on rice, and 27 Tn5 mutants were identified that were either non-pathogenic or showed reduced virulence in rice. Fourteen of the non-pathogenic mutants were also unable to elicit the hypersensitive response (HR) in tobacco and were designated Pth(-)/HR(-) mutants; 13 mutants showed attenuated virulence and were able to induce an HR (Vir(-)/HR(+)). Sequence analysis of the Tn5-tagged genes indicated that the 14 Pth(-)/HR(-) mutants included mutations in hrcC, hrcT, hrcV, hpaP, hrcQ, hrpF, hrpG and hrpX. The 13 Vir(-)/HR(+) mutants included tal-C10c-like (a transcriptional activator-like TAL effector), rpfC (regulator of pathogenicity factors), oxyR (oxidative stress transcriptional regulator), dsbC (disulfide isomerase), opgH (glucan biosynthesis glucosyltransferase H), rfbA (glucose-1 phosphate thymidylyltransferase), amtR (aminotransferase), purF (amidophosphoribosyltransferase), thrC (threonine synthase), trpA (tryptophan synthase alpha subunit) and three genes encoding hypothetical proteins (Xoryp_02235, Xoryp_00885 and Xoryp_22910). Collectively, the 27 Tn5 insertions are located in 21 different open reading frames. Bacterial growth and in planta virulence assays demonstrated that opgH, purF, thrC, trpA, Xoryp_02235, Xoryp_00885 and Xoryp_22910 are candidate virulence genes involved in Xoc pathogenesis. Reduced virulence in 13 mutants was restored to wild-type levels when the cognate gene was introduced in trans. Expression profiles demonstrated that the seven candidate virulence genes were significantly induced in planta, although their roles in Xoc pathogenesis remain unclear. PMID- 22075021 TI - Salvinorin A pretreatment preserves cerebrovascular autoregulation after brain hypoxic/ischemic injury via extracellular signal-regulated kinase/mitogen activated protein kinase in piglets. AB - BACKGROUND: Cerebral hypoxia/ischemia during infant congenital heart surgery is not uncommon and may induce devastating neurologic disabilities persistent over the lifespan. Hypoxia/ischemia-induced cerebrovascular dysfunction is thought to be an important contributor to neurological damage. No pharmacological agents have been found to prevent this. Mitogen activated protein kinase (MAPK), including extracellular signal regulated kinase (ERK), c-Jun-N-terminal kinase, and p38, is thought to contribute to ischemic preconditioning. We investigated whether pretreatment with salvinorin A, the only natural nonopioid kappa receptor agonist, could preserve autoregulation of the pial artery via MAPK. METHODS: The response of the pial artery to hypotension and hypercapnia was monitored in piglets equipped with a closed cranial window before and after hypoxia and ischemia in the presence or absence of U0126, an inhibitor for the protein kinase upstream of ERK, sp600125, an inhibitor of c-Jun-N-terminal kinase or sb203580, an inhibitor of p38. Salvinorin A (10 MUg/kg IV) was administered 30 minutes before hypoxia/ischemia in salvinorin-treated animals. Cerebrospinal fluid samples were collected before and 30 minutes after salvinorin A administration for the measurement of MAPK. Data (n = 5) were analyzed by repeated-measures analysis of variance. RESULTS: Pial artery dilation to hypercapnia and hypotension was blunted after hypoxia/ ischemia but preserved well by pretreatment with salvinorin A. U0126, but not sp600125 or sb203580, abolished the preservative effects of salvinorin A on cerebral vascular autoregulation to hypotension and hypercapnia. The ratio of pERK/ERK in cerebrospinal fluid increased significantly in salvinorin-treated animals, which was inhibited by U0126. CONCLUSIONS: Salvinorin A pretreatment preserves autoregulation of the pial artery to hypotension and hypercapnia after hypoxia/ischemia via ERK in a piglet model. PMID- 22075023 TI - The seven-transmembrane receptor Gpr1 governs processes relevant for the antagonistic interaction of Trichoderma atroviride with its host. AB - Mycoparasitic Trichoderma species are applied as biocontrol agents in agriculture to guard plants against fungal diseases. During mycoparasitism, Trichoderma directly interacts with phytopathogenic fungi, preceded by a specific recognition of the host and resulting in its disarming and killing. In various fungal pathogens, including mycoparasites, signalling via heterotrimeric G proteins plays a major role in regulating pathogenicity-related functions. However, the corresponding receptors involved in the recognition of host-derived signals are largely unknown. Functional characterization of Trichoderma atroviride Gpr1 revealed a prominent role of this seven-transmembrane protein of the cAMP receptor-like family of fungal G-protein-coupled receptors in the antagonistic interaction with the host fungus and governing of mycoparasitism-related processes. Silencing of gpr1 led to an avirulent phenotype accompanied by an inability to attach to host hyphae. Furthermore, gpr1-silenced transformants were unable to respond to the presence of living host fungi with the expression of chitinase- and protease-encoding genes. Addition of exogenous cAMP was able to restore host attachment in gpr1-silenced transformants but could not restore mycoparasitic overgrowth. A search for downstream targets of the signalling pathway(s) involving Gpr1 resulted in the isolation of genes encoding e.g. a member of the cyclin-like superfamily and a small secreted cysteine-rich protein. Although silencing of gpr1 caused defects similar to those of mutants lacking the Tga3 Galpha protein, no direct interaction between Gpr1 and Tga3 was observed in a split-ubiquitin two-hybrid assay. PMID- 22075024 TI - Genomic and antigenic characterization of monomeric autotransporters of Haemophilus parasuis: an ongoing process of reductive evolution. AB - The genome of the highly pathogenic Haemophilus parasuis Nagasaki strain (serovar 5) was sequenced to 99 % completion. A genomic comparison with two other pathogenic serovar 5 H. parasuis strains identified six genes per genome (bmaA1 bmaA6) encoding beta-barrel monomeric autotransporters, bmaA2 and bmaA3 being pseudogenes in at least one strain. The remaining encoded proteins were predicted to belong to the subtilisin (BmaA1 and BmaA4) and cysteine (BmaA5 and BmaA6) protease families. Allelic polymorphism was detected in other H. parasuis strains by comparative genomic hybridization using microarrays. Recombination events were observed, some of them leading to gene disruption in one of the three strains, although synteny around bmaA genes was conserved. These results suggest that bmaA genes are undergoing a process of reductive evolution. To evaluate their use as potential vaccine antigens, the products of the passenger domains of bmaA1, bmaA4, bmaA5 and bmaA6 were produced in Escherichia coli as recombinant proteins. They were detected by immunoblotting using sera of colostrum-deprived piglets recovering from a sublethal infection with H. parasuis (Nagasaki). The existence of specific antibodies after infection with H. parasuis also demonstrated in vivo expression. Using proteomics, only BmaA6 was detected in the in vitro-grown Nagasaki strain. Interestingly, the translocator domain was found in the outer membrane, while the passenger domain was located in supernatants. These results indicate that BmaA proteins could be considered as immunogen candidates to improve H. parasuis vaccines. However, their capacity to confer protective immunity needs to be studied further. PMID- 22075025 TI - Taxon-specific metagenomics of Trichoderma reveals a narrow community of opportunistic species that regulate each other's development. AB - In this paper, we report on the in situ diversity of the mycotrophic fungus Trichoderma (teleomorph Hypocrea, Ascomycota, Dikarya) revealed by a taxon specific metagenomic approach. We designed a set of genus-specific internal transcribed spacer (ITS)1 and ITS2 rRNA primers and constructed a clone library containing 411 molecular operational taxonomic units (MOTUs). The overall species composition in the soil of the two distinct ecosystems in the Danube floodplain consisted of 15 known species and two potentially novel taxa. The latter taxa accounted for only 1.5 % of all MOTUs, suggesting that almost no hidden or uncultivable Hypocrea/Trichoderma species are present at least in these temperate forest soils. The species were unevenly distributed in vertical soil profiles although no universal factors controlling the distribution of all of them (chemical soil properties, vegetation type and affinity to rhizosphere) were revealed. In vitro experiments simulating infrageneric interactions between the pairs of species that were detected in the same soil horizon showed a broad spectrum of reactions from very strong competition over neutral coexistence to the pronounced synergism. Our data suggest that only a relatively small portion of Hypocrea/Trichoderma species is adapted to soil as a habitat and that the interaction between these species should be considered in a screening for Hypocrea/Trichoderma as an agent(s) of biological control of pests. PMID- 22075026 TI - Fumarate reductase is a major contributor to the generation of reactive oxygen species in the anaerobe Bacteroides fragilis. AB - Despite the detrimental role that endogenously generated reactive oxygen species (ROS) may play in bacteria exposed to aerobic environments, very few sources of ROS have been identified in vivo. Such studies are often precluded by the presence of efficient ROS-scavenging pathways, like those found in the aerotolerant anaerobe Bacteroides fragilis. Here we demonstrate that deletion of the genes encoding catalase (Kat), alkylhydroperoxide reductase (AhpC) and thioredoxin-dependent peroxidase (Tpx) strongly inhibits H(2)O(2) detoxification in B. fragilis, thereby allowing for the quantification of ROS production. Exogenous fumarate significantly reduced H(2)O(2) production in a DeltaahpCDeltakatDeltatpx B. fragilis strain, as did deletion of fumarate reductase subunit c (frdC). Deletion of frdC also increased the aerotolerance of a strain lacking superoxide dismutase, indicating that fumarate reductase is a major contributor to ROS formation in B. fragilis exposed to oxygen. PMID- 22075027 TI - Functional analysis of non-ribosomal peptide synthetases (NRPSs) in Trichoderma virens reveals a polyketide synthase (PKS)/NRPS hybrid enzyme involved in the induced systemic resistance response in maize. AB - Trichoderma virens genome harbours genes encoding 22 non-ribosomal peptide synthetases (NRPSs) with at least one complete module (containing adenylation, thiolation and condensation domains) and four PKS/NRPS (polyketide synthase/NRPS) hybrid enzymes. After a primary screen for expression of these 26 genes when mycelia of T. virens are in contact with maize roots, seven genes that are upregulated were selected for further study. Using homologous recombination, loss of-function mutants in six of these were obtained (the seventh, tex2, was acquired from our previous studies). Plant assays in a hydroponics system revealed that all seven mutants retained the ability to internally colonize maize roots. However, a mutation in one of the PKS/NRPS hybrid genes impaired the ability of T. virens to induce the defence response gene pal (phenylalanine ammonia lyase), suggesting a putative role for the associated metabolite product in induced systemic resistance. Interestingly, the mutant retained its ability to induce another defence response gene aos (allene oxide synthase). We thus provide evidence that a PKS/NRPS hybrid enzyme is involved in Trichoderma-plant interactions resulting in induction of defence responses. PMID- 22075028 TI - Streptomyces coelicolor sRNA scr5239 inhibits agarase expression by direct base pairing to the dagA coding region. AB - Transcriptional regulation of primary and secondary metabolism is well-studied in Streptomyces coelicolor, a model organism for antibiotic production and cell differentiation. In contrast, little is known about post-transcriptional regulation and the potential functions of small non-coding RNAs (sRNAs) in this Gram-positive, GC-rich soil bacterium. Here, we report the identification and characterization of scr5239, an sRNA highly conserved in the genus Streptomyces. The sRNA is 159 nt long, composed of five stem-loops, and encoded in the intergenic region between SCO5238 and SCO5239. scr5239 expression is constitutive under several stress and growth conditions but dependent on the nitrogen supply. scr5239 decreases the production of the antibiotic actinorhodin, and represses expression of the extracellular agarase dagA at the post-transcriptional level by direct base pairing to the coding region 33 nt downstream of the ribosome-binding site. PMID- 22075029 TI - Comparative study of Trichoderma gene expression in interactions with tomato plants using high-density oligonucleotide microarrays. AB - Trichoderma spp. are widely used as biopesticides and biofertilizers to control diseases and to promote positive physiological responses in plants. In vitro and in vivo assays with Trichoderma harzianum CECT 2413 (T34), Trichoderma virens Gv29-8 (T87) and Trichoderma hamatum IMI 224801 (T7) revealed that these strains affected the growth and development of lateral roots in tomato plants in different ways. The early expression profiles of these Trichoderma strains were studied after 20 h of incubation in the presence of tomato plants, using a high density oligonucleotide (HDO) microarray, and compared to the profiles in the absence of plants. Out of the total 34 138 Trichoderma probe sets deposited on the microarray, 1077 (3.15 %) showed a significant change of at least 2-fold in expression in the presence of tomato plants. The numbers of probe sets identified in the individual Trichoderma strains were 593 in T. harzianum T34, 336 in T. virens T87 and 94 in T. hamatum T7. Carbohydrate metabolism - the chitin degradation enzymes N-acetylglucosamine-6-phosphate deacetylase, glucosamine-6 phosphate deaminase and chitinase - was the most significantly overrepresented process commonly observed in the three Trichoderma strains in early interactions with tomato plants. Strains T7 and T34, which had similar positive effects on plant development in biological assays, showed a significantly overrepresented hexokinase activity in interaction with tomato. In addition, genes encoding a 40S ribosomal protein and a P23 tumour protein were altered in both these strains. PMID- 22075030 TI - Effects of saliva or serum coating on adherence of Streptococcus oralis strains to titanium. AB - The use of dental implants to treat tooth loss has increased rapidly over recent years. 'Smooth' implants showing high long-term success rates have successively been replaced by implants with rougher surfaces, designed to stimulate rapid osseointegration and promote tissue healing. If exposed in the oral cavity, rougher surfaces may promote bacterial adhesion leading to formation of microbial biofilms which can induce peri-implant inflammation. Streptococcus oralis is an early colonizer of oral surfaces and has been recovered from titanium surfaces in vivo. The purpose of this study was to examine the adherence of clinical strains of S. oralis to titanium with smooth or moderately rough surface topography and to determine the effect of a saliva- or serum-derived coating on this process. Adherence was studied using a flow-cell system with confocal laser scanning microscopy, while putative adhesins were analysed using proteomics of bacterial cell wall proteins. This showed that adherence to moderately rough surfaces was greater than to smooth surfaces. Serum did not promote binding of any of the studied S. oralis strains to titanium, whereas a saliva coating increased adherence in two of three strains tested. The higher level of adherence to the moderately rough surfaces was maintained even in the presence of a saliva coating. The S. oralis strains that bound to saliva expressed an LPXTG-linked protein which was not present in the non-adherent strain. Thus strains of S. oralis differ in their capacity to bind to saliva-coated titanium and we propose that this is due to differential expression of a novel adhesin. PMID- 22075031 TI - Alanine racemase mutants of Mycobacterium tuberculosis require D-alanine for growth and are defective for survival in macrophages and mice. AB - Alanine racemase (Alr) is an essential enzyme in most bacteria; however, some species (e.g. Listeria monocytogenes) can utilize d-amino acid transaminase (Dat) to generate d-alanine, which renders Alr non-essential. In addition to the conflicting reports on gene knockout of alr in Mycobacterium smegmatis, a recent study concluded that depletion of Alr does not affect the growth of M. smegmatis. In order to get an unambiguous answer on the essentiality of Alr in Mycobacterium tuberculosis and validate it as a drug target in vitro and in vivo, we have inactivated the alr gene of M. tuberculosis and found that it was not possible to generate an alr knockout in the absence of a complementing gene copy or d-alanine in the growth medium. The growth kinetics of the alr mutant revealed that M. tuberculosis requires very low amounts of d-alanine (5-10 ug ml(-1)) for optimum growth. Survival kinetics of the mutant in the absence of d-alanine indicated that depletion of this amino acid results in rapid loss of viability. The alr mutant was found to be defective for growth in macrophages. Analysis of phenotype in mice suggested that non-availability of d-alanine in mice leads to clearance of bacteria followed by stabilization of bacterial number in lungs and spleen. Additionally, reversal of d-cycloserine inhibition in the presence of d-alanine in M. tuberculosis suggested that Alr is the primary target of d-cycloserine. Thus, Alr of M. tuberculosis is a valid drug target and inhibition of Alr alone should result in loss of viability in vitro and in vivo. PMID- 22075032 TI - The year in burns 2010. AB - For 2010, roughly 1446 original burn research articles were published in scientific journals using the English language. This article reviews those with the most impact on burn treatment according to the Editor of one of the major journals (Burns) and his colleagues. As in previous reviews, articles were divided into the following topic areas: epidemiology, demographics of injury, wound characterisation and treatment, critical care, inhalation injury, infection, metabolism and nutrition, psychological considerations, pain and itching management, rehabilitation and long-term outcomes, and burn reconstruction. Each paper is considered very briefly, and the reader is referred to full manuscripts for details. PMID- 22075033 TI - Flow cytometry analysis: a quantitative method for collagen VI deficiency screening. AB - Mutations in COL6A1, COL6A2 and COL6A3 genes result in collagen VI myopathies: Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and intermediate phenotypes. At present, none of the existing diagnostic techniques for evaluating collagen VI expression is quantitative, and the detection of subtle changes in collagen VI expression remains challenging. We investigated flow cytometry analysis as a means of quantitatively measuring collagen VI in primary fibroblasts and compared this method with the standard method of fibroblast collagen VI immunohistochemical analysis. Eight UCMD and five BM molecularly confirmed patients were studied and compared to five controls. Flow cytometry analysis consistently detected a reduction of collagen VI of at least 60% in all UCMD cases. In BM cases the levels of collagen VI were variable but on average 20% less than controls. Flow cytometry analysis provides an alternative method for screening for collagen VI deficiency at the protein level in a quantitative, time and cost-effective manner. PMID- 22075034 TI - C-Mantec: a novel constructive neural network algorithm incorporating competition between neurons. AB - C-Mantec is a novel neural network constructive algorithm that combines competition between neurons with a stable modified perceptron learning rule. The neuron learning is governed by the thermal perceptron rule that ensures stability of the acquired knowledge while the architecture grows and while the neurons compete for new incoming information. Competition makes it possible that even after new units have been added to the network, existing neurons still can learn if the incoming information is similar to their stored knowledge, and this constitutes a major difference with existing constructing algorithms. The new algorithm is tested on two different sets of benchmark problems: a Boolean function set used in logic circuit design and a well studied set of real world problems. Both sets were used to analyze the size of the constructed architectures and the generalization ability obtained and to compare the results with those from other standard and well known classification algorithms. The problem of overfitting is also analyzed, and a new built-in method to avoid its effects is devised and successfully applied within an active learning paradigm that filter noisy examples. The results show that the new algorithm generates very compact neural architectures with state-of-the-art generalization capabilities. PMID- 22075035 TI - Working memory and response selection: a computational account of interactions among cortico-basalganglio-thalamic loops. AB - Cortico-basalganglio-thalamic loops are involved in both cognitive processes and motor control. We present a biologically meaningful computational model of how these loops contribute to the organization of working memory and the development of response behavior. Via reinforcement learning in basal ganglia, the model develops flexible control of working memory within prefrontal loops and achieves selection of appropriate responses based on working memory content and visual stimulation within a motor loop. We show that both working memory control and response selection can evolve within parallel and interacting cortico basalganglio-thalamic loops by Hebbian and three-factor learning rules. Furthermore, the model gives a coherent explanation for how complex strategies of working memory control and response selection can derive from basic cognitive operations that can be learned via trial and error. PMID- 22075036 TI - Evaluation of the flocculation performance of carboxymethyl chitosan-graft polyacrylamide, a novel amphoteric chemically bonded composite flocculant. AB - In the present work, a novel amphoteric chemically bonded composite flocculant (carboxymethyl chitosan-graft-polyacrylamide, denoted as CMC-g-PAM) was successfully prepared and used to flocculate the kaolin suspension. The flocculation performance of CMC-g-PAM in acidic, neutral, and alkaline conditions was systematically evaluated by light scattering in combination with fractal theory, as well as by traditional turbidity and zeta potential measurements. Based on the experimental facts from in situ size and fractal dimension measurements, different flocculation mechanisms play key roles at various pH levels, resulting in substantially varied flocculation kinetic processes under three pH conditions. In acidic condition, patching was the main mechanism involved in the opposite zeta potential between CMC-g-PAM and the kaolin suspension. A flat configuration was favored when the polymeric flocculant was adsorbed onto the particle surface, leading to a slower initial floc growth rate but larger and denser flocs. Bridging was the dominant mechanism in neutral and alkaline conditions. A faster initial rate of bridging resulted in smaller and more open floc structures. A rearrangement process in neutral pH subsequently led to more compact flocs, whereas no restructuration of flocs occurred in alkaline conditions because of the electrostatic repulsion of the same negative charges on the flocculant and particles. PMID- 22075037 TI - Multi-cycle bioregeneration of spent perchlorate-containing macroporous selective anion-exchange resin. AB - Ion exchange using perchlorate-selective resin is possibly the most feasible technology for perchlorate removal from water. However, in current water treatment applications, selective resins are used once and then incinerated, making the ion-exchange process economically and environmentally unsustainable. A new concept has been developed involving the biological regeneration of resin containing perchlorate. This concept involves directly contacting perchlorate containing resins with a perchlorate-reducing microbial culture. In this research, the feasibility of multi-cycle loading and bioregeneration of a macroporous perchlorate-selective resin was investigated. Loading and bioregeneration cycles were performed, using a bench-scale fermenter and a fluidized bed reactor followed by fouling removal and disinfection of the resin. The results revealed that selective macroporous resin can be employed successfully in a consecutive loading-bioregeneration ion-exchange process. Loss of resin capacity stabilized after a few cycles of bioregeneration, indicating that the number of loading and bioregeneration cycles that can be performed is likely greater than the five cycles tested. The results also revealed that most of the capacity loss in the resin is due to perchlorate buildup from previous regeneration cycles. The results further indicated that as the bioregeneration progresses, clogging of the resin pores results in strong mass transfer limitation in the bioregeneration process. PMID- 22075038 TI - Genetic characterization of three Cuban Trichomonas vaginalis virus. Phylogeny of Totiviridae family. AB - Trichomonas vaginalis can be infected with double stranded RNA (dsRNA) viruses known as T. vaginalis virus (TVV). This viral infection may have important implications for trichomonal virulence and disease pathogenesis. In this study we identified and genetic characterized three strains of TVVs isolated from T. vaginalis in Cuba. The three new predicted sequences of capsid protein and RNA dependent RNA polymerase amounted to the previously determined 20 TVV sequences and other 21 viruses of Totiviridae family were used for a phylogenetic analysis. Four distinct monophyletic clades are shown in a phylogenetic tree. One corresponds with TVVs, other with Victorivirus, Leishmaniavirus and Eimeria brunetti virus and, other with viruses of the genus Totivirus and the last with Giardiavirus. The E. brunetti virus is identified in the phylogenetic tree as independent taxon between Leishmaniavirus and Victorivirus isolates, most closely related to Victorivirus. TVV constitute a monophyletic cluster distinguishable from all other viruses in Totiviridae family. This result suggested that TVV may be grouped in a separated genus and not inside of Giardiavirus. TVVs appear to be more closely related to protozoan viruses in the genus Leishmaniavirus and to fungal viruses in the genus Victorivirus than to other protozoan and fungal viruses in Giardiavirus and Totivirus. Among TVVs, four main groups can be recognized within Trichomonasvirus cluster, which correspond with the previous species classification proposed. Further studies, with more TVV strains, especially TVV3 and 4 strains, are needed in order to determine the phylogenetic relationship among Trichomonasvirus genus and specifically if TVV2 and 3 each also constitute a well-delimited group. PMID- 22075039 TI - Effect of the diclazuril on Hsp90 in the second-generation merozoites of Eimeria tenella. AB - Eimeria tenella (E. tenella) is one of the most virulent pathogens of coccidiosis. In apicomplexan parasites, Hsp90 (Heat shock protein 90) is essential for the invasion and survival in host cells. In this study, the effect of diclazuril, an effective benzeneacetonitrile anticoccidial agent, on the expression of Hsp90 in the second-generation merozoites of E. tenella was investigated. We inoculated 8 * 10(4) oocysts/chicken suspended in 1 ml of distilled water, and chickens were challenged with E. tenella oocysts and provided with normal feed as Control group; chickens challenged with E. tenella oocysts and provided with 1mg/kg diclazuril in feed from 96 h to 120 h after inoculation as treatment group. Then the second-generation merozoites were obtained after 120 h from the infected caeca. Our results showed that the transcription level of mzHsp90 was reduced by 29.7% in the diclazuril treatment group, accompanied by reduced level of mzHsp90 protein in second-generation merozoites prepared from infected chickens. We also found that the subcellular localization of mzHsp90 was more dispersed in these merozoites. Moreover, we demonstrated that the effects of diclazuril on mzHsp90 expression were direct by in vitro experiments. Taken together, our data provide insights into the molecular mechanisms of diclazuril in the chemotherapy of E. tenella, and suggest that mzHsp90 represents a promising target for the intervention with E. tenella infection. PMID- 22075040 TI - Pharmacological characterization of the Haemonchus contortus GABA-gated chloride channel, Hco-UNC-49: modulation by macrocyclic lactone anthelmintics and a receptor for piperazine. AB - Invertebrate ligand-gated chloride channels are well recognized as important targets for several insecticides and anthelmintics. Hco-UNC-49 is a GABA-gated chloride channel from the parasitic nematode Haemonchus contortus and is an orthologue to the neuromuscular receptor (Cel-UNC-49) from the free-living nematode Caenorhabditis elegans. While the receptors from the two nematodes are similar in sequence, they exhibit different sensitivities to GABA which may reflect differences in in vivo function. The aim of the current study was to further characterize the pharmacology of the Hco-UNC-49 receptor by examining its sensitivity to various insecticides and anthelmintics using two-electrode voltage clamp. Specifically, the insecticides fipronil and picrotoxin appear to inhibit the channel in a similar manner. The IC(50) of picrotoxin on the homomeric channel was 3.65 +/- 0.64 MUM and for the heteromeric channel was 134.56 +/- 44.12 MUM. On the other hand, dieldrin, a well-known insect GABA receptor blocker, had little effect on the UNC-49 channel. The anthelmintics ivermectin and moxidectin both moderately potentiated the activation of Hco-UNC-49 by GABA, while piperazine was able to directly activate both the Hco-UNC-49 homomeric and heteromeric channels with EC(50) values of 6.23 +/- 0.45 mM and 5.09 +/- 0.32 mM, respectively. This piperazine current was reversibly blocked by picrotoxin which demonstrates that the anthelmintic specifically targets Hco-UNC-49. These results demonstrate that Hco-UNC-49 exhibits binding sites for several molecules including piperazine and macrocyclic lactone anthelmintics. In addition, this is the first report of the heterologous expression and subsequent characterization of a receptor for piperazine. PMID- 22075041 TI - Pharmacokinetics of a new ivermectin/praziquantel oil suspension after intramuscular administration in pigs. AB - A new oil suspension containing 0.15% ivermectin and 15% praziquantel for intramuscular injection was developed, and corresponding pharmacokinetics studies were conducted in swine. The combination product is a white- to cream-colored oil suspension and its physical properties such as settling volume ratio, redispersibility, syringeability and flowability are well consistent with the Technical Standards by the Ministry of Agriculture of the People's Republic of China. The pharmacokinetic study consists of two parts. First, the experiments were carried out to compare the pharmacokinetic parameters of the combination product and those same products with praziquantel or ivermectin removed merely. The results showed that no significant change in the major pharmacokinetic parameters (t(1/2z), T(max), C(max), AUC(INF), TimeDur) was observed when either of the component was removed from the combination product, indicating that ivermectin and praziquantel do not interfere with each other when being used together. Second, the pharmacokinetics of the combination product were compared with those of their respective single product. The results showed that the C(max) (15.94 ng/mL) of ivermectin in combination product was 9.01 times higher than the single product, while the AUC(INF) (1925.61 ng h/mL) was 6.02 times higher. Meanwhile, the C(max) (1.48 MUg/mL), AUC(INF) (17.08MUgh/mL), t(1/2z) (20.25 h), TimeDur3 (42.01 h) and TimeDur4 (16.60 h) of praziquantel in combination product were improved with a factor of 5.48, 13.66, 8.58, 10.10 and 7.31 times when compared with the single product, respectively. Therefore, the efficacy of the combination product was significantly prolonged, especially for praziquantel, so that comprehensive efficacy of controlling parasites sensitive to ivermectin and praziquantel can be achieved with one-single use of it. PMID- 22075042 TI - Starvation and overwinter do not affect the reproductive fitness of Rhipicephalus sanguineus. AB - Rhipicephalus sanguineus is the most widespread tick in the world, being able to survive under different climate conditions. In this study, the longevity of R. sanguineus was investigated under laboratory and natural climate conditions in southern Italy. Moreover, the reproductive fitness of females after overwintering was assessed. In the environment, unfed larvae, nymphs and adults were able to survive for up to 34, 40 and 385 days, respectively. However, the longevity of larvae (44 days), nymphs (54 days) and adults (584 days) in the laboratory was longer. Adult ticks that had overwintered under natural climate conditions were able to feed and give rise to viable larvae, after 40 weeks of starvation. Thereby, it is demonstrated that R. sanguineus is able to overwinter in southern Italy, without any prejudice to its fitness. These findings advance our knowledge on the natural history of R. sanguineus in nature and provide new insights into the epidemiology of certain tick-borne diseases in southern Europe as well as into the risk for their introduction in northern European countries. PMID- 22075043 TI - Safety and efficacy against fourth-stage gastrointestinal nematode larvae, of monepantel in 6-week old lambs. AB - A controlled, blinded study was undertaken in 6-week old, pre-weaned lambs to demonstrate the safety and efficacy against fourth-stage gastrointestinal nematode larvae, of monepantel administered per os at 2.5mg/kg body weight. Worm burdens of 10 monepantel-treated lambs were compared to those from 10 untreated control lambs. Geometric mean derived efficacies of 100, 100, 96.4 and 99.9% were demonstrated against Haemonchus contortus, Teladorsagia spp., Cooperia curticei and Trichostrongylus colubriformis, respectively. These results, considered in the light of an earlier series of studies demonstrating the efficacy of monepantel in older animals, and an absence of any adverse events, provides strong support for the use of monepantel as a safe and effective anthelmintic in lambs from six weeks of age. PMID- 22075044 TI - Massive aquaresis after tolvaptan administration and albumin infusion in a patient with alcoholic cirrhosis. PMID- 22075045 TI - Thrombosis in suspected heparin-induced thrombocytopenia occurs more often with high antibody levels. AB - OBJECTIVE: The study objective was to determine whether higher antiplatelet factor 4 (PF4)/heparin antibody levels using an enzyme-linked immunosorbent assay are associated with more frequent thrombotic events in patients with clinically suspected heparin-induced thrombocytopenia. Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction. An enzyme-linked immunosorbent assay detects anti-PF4/heparin antibodies to support a suspected clinical diagnosis of heparin-induced thrombocytopenia. The utility of quantitative enzyme-linked immunosorbent assay results is uncertain. METHODS: Our single-centered study evaluated quantitative anti-PF4/heparin antibody levels using an enzyme-linked immunosorbent assay in consecutive hospitalized patients with a clinical suspicion of heparin-induced thrombocytopenia and positive anti-PF4/heparin antibody levels between July 2003 and December 2006. RESULTS: Overall, anti PF4/heparin antibody values were available for 318 patients with clinically suspected heparin-induced thrombocytopenia. The median level was 0.85 optical density units (range 0.31-4.0). The overall rate of arterial or venous thrombosis was 23.3%. A 1-unit increase in anti-PF4/heparin antibody level was associated with an approximate doubling in the odds of thrombosis by 30 days (odds ratio, 1.9; 95% confidence interval, 1.5-2.6; P=.0001). The proportion of patients with pulmonary embolism increased with higher anti-PF4/heparin antibody levels. CONCLUSION: Higher levels of anti-PF4/heparin antibody are associated with increased thrombosis risk among patients with clinically suspected heparin induced thrombocytopenia and might have clinical utility for prediction of true heparin-induced thrombocytopenia and the development of thrombosis. PMID- 22075046 TI - Callosal warning syndrome. AB - OBJECTIVE: To report the clinical and imaging findings in a patient with an initial fluctuating disconnection syndrome due to corpus callosal ischemia that ultimately culminated in infarction with persistent symptoms. CASE REPORT: A 40 year-old, hypertensive, right-handed man presented with transient, stereotyped symptoms of corpus callosal disconnection (intermanual conflict, apraxia, dysgraphia and construction difficulties in his left hand). Serial magnetic resonance imaging scans demonstrated the ischemic nature of the initial fluctuating symptoms and later showed callosal infarction when the symptoms were persistent. Magnetic resonance angiogram did not reveal significant stenosis or occlusion of the internal carotid or proximal portion of anterior cerebral arteries. Patient received standard treatment for ischemic stroke and at follow up 1 month later, had mild left hand apraxia, dysgraphia and construction difficulties. CONCLUSION: The case highlights the unusual occurrence of crescendo transient ischemic attacks culminating in infarction in the location of corpus callosum. We have termed this novel stroke syndrome as 'callosal warning syndrome' as the temporal profile was quite indistinguishable from that of relatively well-known stroke warning syndromes in the location of internal capsule and pontine tegmentum. PMID- 22075047 TI - Effect of micro lesions of the basal ganglia on ballistic movements in patients with deep brain stimulation. AB - Bradykinesia and hypokinesia are the prominent symptoms of substantia nigra degeneration in Parkinson's disease (PD). In segmental dystonia, movements of not affected limbs are not impaired. Here we studied the impact of the mere implantation of stimulation electrodes on the performance of fast movements in these two groups. We investigated 9 PD patients with subthalamic electrodes and 9 patients with segmental dystonia with electrodes in the globus pallidus internum. Patients were studied on the first postoperative day without electrical stimulation of the electrodes. Subjects had to perform boxing movements with either touching the target or stopping the fist in front of the target. PD subjects performed significantly faster movements in the touch-task only as compared to dystonic patients. No difference was seen in the stopping task. In conclusion, our findings suggest that a small subthalamic lesion in individuals with PD specifically reverses bradykinesia during simple ballistic movements (touch) but not during complex ones requiring more pre-programming (no-touch paradigm). PMID- 22075048 TI - New novel mutation of the ATP7B gene in a family with Wilson disease. AB - Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The WD gene codes for a copper transporting P-type ATPase (ATP7B) are located on chromosome 13q14.3. Mutation of this gene disrupts copper homeostasis, resulting in the accumulation of copper in the liver, brain, kidneys and corneas and copper toxication at these sites. Since the detection of the WD gene in 1993, approximately 300 disease-specific muations have been identified. We recently evaluated a Korean family with WD. The proband, a 17-year-old boy, visited our hospital due to abnormal behaviors including generalized slow movement, dysphagia, drooling and ataxia. Laboratory results revealed decreases in serum copper and ceruloplasmin and an increase in urinary excretion of copper. He had liver cirrhosis, brain lesions and Kayser-Fleischer corenal rings. Molecular genetic analysis of the ATP7B gene demonstrated that he was heterozygous for deletion mutation c.2697_2723del27 in exon 11. Further study of family members revealed that his father and younger brother had the same mutation. The c.2697_2723del27 deletion mutation in exon 11 has not yet been reported as a causative muation of WD and is an in-frame deletion not expected to lead to a frame shift. Therefore, we report a novel mutation of the ATP7B gene in a family with WD. PMID- 22075049 TI - Tissue-specific accumulation of cadmium and its effects on antioxidative responses in Japanese flounder juveniles. AB - This study investigated the accumulation of cadmium (0-8 mg Cd L-1) and its toxicological effects on oxidative stress biomarkers in different tissues of Japanese flounder juveniles. Following Cd exposure for 28 d, accumulation of Cd in fish was dose-dependent and tissue-specific, with the greatest accumulation in the liver, followed by the kidney, gill, and muscle. Although the gill and liver mounted active antioxidant responses at >= 4 mg L-1 Cd including a decrease in glutathione level and GST and GPx activities, the antioxidant response failed to prevent lipid peroxidation induction in these organs. In the kidney, increased GPx and GST activities and decreased SOD activity were observed in fish exposed to high Cd concentrations, but LPO levels did not significantly differ among the exposure concentrations. The gill was most sensitive to oxidative damage, followed by the liver; the kidney was the least affected tissue. PMID- 22075050 TI - Use of custom-made stockings to control postoperative leg and foot edema following free tissue transfer and external fixation of fractures. AB - Patients with lower extremity trauma treated with free tissue transfer and external fixation of fractures almost always have postoperative edema of the foot and leg. Although compressive elastic stockings have been advised to be worn by patients with venous or lymphatic insufficiency, no such stocking has been described for postoperative use by patients with external fixators. The aim of the present report was to describe a custom-made elastic compression stocking for patients who have undergone soft tissue reconstruction and fracture fixation with external fixators. These custom-made stockings can help to decrease postoperative edema during the nonambulatory and nonweight-bearing ambulatory period. They are easy to apply, affordable, and can be tailored from regular compression stockings according to the needs of the patients. PMID- 22075051 TI - Effect of silver nanoparticles in crop plants Phaseolus radiatus and Sorghum bicolor: media effect on phytotoxicity. AB - Understanding some adverse effects of nanoparticles in edible crop plants is a matter of importance because nanoparticles are often released into soil environments. We investigated the phytotoxicity of silver nanoparticles (AgNPs) on the important crop plants, Phaseolus radiatus and Sorghum bicolor. The silver nanoparticles were selected for this study because of their OECD designation as a priority nanomaterial. The toxicity and bioavailability of AgNPs in the crop plant species P. radiatus and S. bicolor were evaluated in both agar and soil media. The seedling growth of test species was adversely affected by exposure to AgNPs. We found evidence of nanoparticle uptake by plants using electron microscopic studies. In the agar tests, P. radiatus and S. bicolor showed a concentration dependent-growth inhibition effect. Measurements of the growth rate of P. radiatus were not affected in the soil studies by impediment within the concentrations tested herein. Bioavailability of nanoparticles was reduced in the soil, and the dissolved silver ion effect also differed in the soil as compared to the agar. The properties of nanoparticles have been shown to change in soil, so this phenomenon has been attributed to the reduced toxicity of AgNPs to plants in soil medium. The application of nanoparticles in soil is a matter of great importance to elucidate the terrestrial toxicity of nanoparticles. PMID- 22075052 TI - Development of a new time-integrative sampler using in situ solvent extraction. AB - Despite the great success of time-weighted average passive sampling of hydrophobic contaminants, such as PCBs and PAHs, the sampling of polar organic compounds still presents a challenge because the equilibrium between water and most sampling phases is attained in a relatively short time. In this study, we proposed a new time-integrative sampler using in situ solvent extraction (TISIS) for polar organic chemicals. The sampler was composed of a 15 cm poly(dimethylsiloxane) (PDMS) tubing, with an internal diameter of 0.5 mm and wall thickness of 0.5 mm, through which an extraction solvent (acetonitrile) was passed. Four polar organic contaminants, caffeine, atrazine, diuron and 17alpha ethynylestradiol, were chosen for the evaluation of the performance of the sampler. Without the use of in situ solvent extraction, the PDMS tubing when exposed to a constant aqueous concentration of the four model compounds was able to linearly accumulate those compounds for less than 12 h and equilibrium between the PDMS tubing and water was attained in 2 d under our laboratory conditions. However, TISIS when exposed to a constant aqueous concentration was able to linearly accumulate all the model compounds without any exposure time limitation. The measured sampling rates at three different extraction flow rates (0.2, 0.5, 1.5 mL min(-1)) were similar, regardless of the chemicals, indicating that the overall mass transfer from aqueous solution to the extraction solvent was most likely dominated by partitioning to the PDMS tubing and the internal diffusion within PDMS. In addition, a pulsed exposure experiment confirmed that TISIS operated in a time-integrative mode when the environmental concentration was highly fluctuated. PMID- 22075053 TI - Fecal coliforms, caffeine and carbamazepine in stormwater collection systems in a large urban area. AB - Water samples from streams, brooks and storm sewer outfall pipes that collect storm waters across the Island of Montreal were analyzed for caffeine, carbamazepine and fecal coliforms. All samples contained various concentrations of these tracers, indicating a widespread sanitary contamination in urban environments. Fecal coliforms and caffeine levels ranged over several orders of magnitude with a modest correlation between caffeine and fecal coliforms (R(2) value of 0.558). An arbitrary threshold of 400 ng caffeine L(-1) allows us to identify samples with an elevated fecal contamination, as defined by more than 200 colony-forming units per 100 mL (cfu 100 mL(-1)) of fecal coliforms. Low caffeine levels were sporadically related to high fecal coliform counts. Lower levels of caffeine and fecal coliforms were observed in the brooks while the larger streams and storm water discharge points contained over ten times more. The carbamazepine data showed little or no apparent correlation to caffeine. These data suggest that this storm water collection system, located in a highly urbanized urban environment, is widely contaminated by domestic sewers as indicated by the ubiquitous presence of fecal contaminants as well as caffeine and carbamazepine. Caffeine concentrations were relatively well correlated to fecal coliforms, and could potentially be used as a chemical indicator of the level of contamination by sanitary sources. The carbamazepine data was not significantly correlated to fecal coliforms and of little use in this dataset. PMID- 22075054 TI - Combined effects of deltamethrin, temperature and salinity on oxidative stress biomarkers and acetylcholinesterase activity in the black tiger shrimp (Penaeus monodon). AB - This study aimed to investigate the interactions of two abiotic factors (temperature and salinity) and deltamethrin (pyrethroid pesticide) exposure on some oxidative stress biomarkers as well as on acetylcholinesterase activity (AChE) in hepatopancreas, gills and muscle of black tiger shrimp (Penaeus monodon). A combination of three temperatures (24, 29 and 34 degrees C), two salinities (15 and 25 ppt), and the absence or presence of 0.1 MUg L(-1) deltamethrin was applied on shrimp during 4 d under laboratory conditions. Lipid peroxidation level (LPO) and glutathione S-transferase activity (GST) were not affected by combined effect of temperature, salinity and deltamethrin in any of the studied tissues. Deltamethrin impaired other tested oxidative stress biomarkers, i.e. total glutathione (tGSH), catalase (CAT), glutathione peroxidase (GPx). tGSH level significantly increased in hepatopancreas due to deltamethrin exposure mainly at 34 degrees C, while pesticide effects on tGSH and CAT activity in gills were influenced by both temperature and salinity. In addition, GPx activity in hepatopancreas decreased after deltamethrin treatment mainly at 24 degrees C. Finally, AChE in muscle was strongly inhibited by deltamethrin at all tested temperatures and salinities. These novel findings demonstrate that interactions between abiotic factors and a commonly used pesticide exposure should be taken into account when analyzing some widespread biomarkers in black tiger shrimp. PMID- 22075055 TI - Effectiveness of different methods of resistance exercises in lateral epicondylosis--a systematic review. AB - STUDY DESIGN: Systematic Review. INTRODUCTION: Lateral epicondylosis (LE) is relatively common with an annual incidence in the general population of 1% to 3%. Systematic reviews have identified exercise is effective, but have not established specific exercise parameters. PURPOSE: The purpose of this systematic review was to synthesize the quality and content of clinical research addressing type and dosage of resistance exercises in lateral epicondylosis. METHODS: Computerized bibliographic databases (1990-2010) were searched using relevant keywords; bibliographies of included papers were hand searched. Of 594 screened abstracts, 11 articles (12 studies) met inclusion criteria. Articles were randomly allocated to pairs of reviewers who independently verified data extraction and appraised the full text, using a structured critical appraisal tool with 24 items. Data extraction was limited by a lack of consistent reporting of elements of exercise dosage. RESULTS: The mean quality rating of the studies was 72%, with 2 papers exceeding 75% quality. Of the 12 studies, 9 addressed the effects of isotonic (eccentric/concentric) exercises, 2 studied the effect of isometric and one studied isokinetic exercises. The exercise programs ranged over a period of 4 to 52 weeks. Exercises were prescribed 1 to 6 times per day, with an average duration of 15 minutes per session, and average of 15 repetitions (range: 3 to 50), with 1 to 4 sets per session. CONCLUSION: All the studies reported that resistance exercise resulted in substantial improvement in pain and grip strength; eccentric exercise was most studied. Strengthening using resistance exercises is effective in reducing pain and improving function for lateral epicondylosis but optimal dosing is not defined. LEVEL OF EVIDENCE: 2a. PMID- 22075056 TI - Central chemoreflex ventilatory responses in humans following passive heat acclimation. AB - Since there is temperature dependence of pulmonary ventilation (V(E)) in response to the normal modulators (i.e. [Formula: see text] , [Formula: see text] ), it was asked in this study if passive heat acclimation (HA) modifies the human central chemoreflex ventilatory response to CO(2). Nine males performed normothermic- and hyperthermic modified Read re-breathing tests before and after HA. Heat acclimation consisted of 2hday(-1) exposures to 50 degrees C and 20% RH for 10 consecutive days and each exposure elevated rectal temperature to between 38.5 and 39.0 degrees C. Ventilatory recruitment thresholds (VRTs) and central chemosensitivity were assessed before and after HA during normothermia with an oesophageal temperature (T(es)) of ~37 degrees C and in hyperthermia when T(es) was 38.5-39.0 degrees C. Results showed VRT and central chemosensitivities were unaltered by HA (p>=0.375) and hyperthermia increased pre- (p=0.010) but not post acclimation (p=0.332) central chemosensitivity. Additionally, during hyperthermia V(E) became progressively greater (p=0.027) relative to corresponding normothermic values in the re-breathing tests. In conclusion, the ventilatory response to hyperoxic CO(2) was unaltered by heat Acclimation State. PMID- 22075057 TI - Focal adhesion kinase inhibitors are potent anti-angiogenic agents. AB - Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase and scaffold protein localized to focal adhesions, is uniquely positioned at the convergence point of integrin and receptor tyrosine kinase signal transduction pathways. FAK is overexpressed in many tumor cells, hence various inhibitors targeting its activity have been tested for anti-tumor activity. However, the direct effects of these pharmacologic agents on the endothelial cells of the vasculature have not been examined. Using primary human umbilical vein endothelial cells (HUVEC), we characterized the effects of two FAK inhibitors, PF-573,228 and FAK Inhibitor 14 on essential processes for angiogenesis, such as migration, proliferation, viability and endothelial cell tube formation. We observed that treatment with either FAK Inhibitor 14 or PF-573,228 resulted in reduced HUVEC viability, migration and tube formation in response to vascular endothelial growth factor (VEGF). Furthermore, we found that PF-573,228 had the added ability to induce apoptosis of endothelial cells within 36 h post-drug administration even in the continued presence of VEGF stimulation. FAK inhibitors also resulted in modification of the actin cytoskeleton within HUVEC, with observed increased stress fiber formation in the presence of drug. Given that endothelial cells were sensitive to FAK inhibitors at concentrations well below those reported to inhibit tumor cell migration, we confirmed their ability to inhibit endothelial derived FAK autophosphorylation and FAK-mediated phosphorylation of recombinant paxillin at these doses. Taken together, our data indicate that small molecule inhibitors of FAK are potent anti-angiogenic agents and suggest their utility in combinatorial therapeutic approaches targeting tumor angiogenesis. PMID- 22075058 TI - Ultrafast soft X-ray photoelectron spectroscopy at liquid water microjets. AB - Since the pioneering work of Kai Siegbahn, electron spectroscopy for chemical analysis (ESCA) has been developed into an indispensable analytical technique for surface science. The value of this powerful method of photoelectron spectroscopy (PES, also termed photoemission spectroscopy) and Siegbahn's contributions were recognized in the 1981 Nobel Prize in Physics. The need for high vacuum, however, originally prohibited PES of volatile liquids, and only allowed for investigation of low-vapor-pressure molecules attached to a surface (or close to a surface) or liquid films of low volatility. Only with the invention of liquid beams of volatile liquids compatible with high-vacuum conditions was PES from liquid surfaces under vacuum made feasible. Because of the ubiquity of water interfaces in nature, the liquid water-vacuum interface became a most attractive research topic, particularly over the past 10 years. PES studies of these important aqueous interfaces remained significantly challenging because of the need to develop high-pressure PES methods. For decades, ESCA or PES (termed XPS, for X ray photoelectron spectroscopy, in the case of soft X-ray photons) was restricted to conventional laboratory X-ray sources or beamlines in synchrotron facilities. This approach enabled frequency domain measurements, but with poor time resolution. Indirect access to time-resolved processes in the condensed phase was only achieved if line-widths could be analyzed or if processes could be related to a fast clock, that is, reference processes that are fast enough and are also well understood in the condensed phase. Just recently, the emergence of high harmonic light sources, providing short-wavelength radiation in ultrashort light pulses, added the dimension of time to the classical ESCA or XPS technique and opened the door to (soft) X-ray photoelectron spectroscopy with ultrahigh time resolution. The combination of high harmonic light sources (providing radiation with laserlike beam qualities) and liquid microjet technology recently enabled the first liquid interface PES experiments in the IR/UV-pump and extreme ultraviolet-probe (EUV-probe) configuration. In this Account, we highlight features of the technology and a number of recent applications, including extreme states of matter and the discovery and detection of short-lived transients of the solvated electron in water. Properties of the EUV radiation, such as its controllable polarization and features of the liquid microjet, will enable unique experiments in the near future. PES measures electron binding energies and angular distributions of photoelectrons, which comprise unique information about electron orbitals and their involvement in chemical bonding. One of the future goals is to use this information to trace molecular orbitals, over time, in chemical reactions or biological transformations. PMID- 22075059 TI - Levator ani subtended volume: a novel parameter to evaluate levator ani muscle laxity in pelvic organ prolapse. AB - OBJECTIVE: We describe a new parameter based on magnetic resonance 3-dimensional (3D) reconstructions proposed to evaluate levator ani muscle (LAM) laxity in women with pelvic organ prolapse (POP). STUDY DESIGN: This is an institutional review board-approved, retrospective chart review of 35 women with POP, stages I IV. The 3D Slicer software package was used to perform 2-dimensional and 3D measurements and the levator ani subtended volume (LASV) was described. Basically, the LASV represents the volume contained by LAM between 2 planes, which coincides with pubococcygeal line and H line. Correlations among measurements, ordinal POP stages, POP Quantification (POPQ) individual measurements, and validated questionnaires were performed. RESULTS: The LASV differentiated major (III and IV) from minor (I and II) POPQ stages, which positively correlated to POP stages and POPQ individual measurements. CONCLUSION: The LASV is a promising parameter to evaluate the LAM laxity. PMID- 22075060 TI - Evaluation of simulation training in cardiothoracic surgery: the Senior Tour perspective. AB - OBJECTIVE: The study objective was to introduce senior surgeons, referred to as members of the "Senior Tour," to simulation-based learning and evaluate ongoing simulation efforts in cardiothoracic surgery. METHODS: Thirteen senior cardiothoracic surgeons participated in a 21/2-day Senior Tour Meeting. Of 12 simulators, each participant focused on 6 cardiac (small vessel anastomosis, aortic cannulation, cardiopulmonary bypass, aortic valve replacement, mitral valve repair, and aortic root replacement) or 6 thoracic surgical simulators (hilar dissection, esophageal anastomosis, rigid bronchoscopy, video-assisted thoracoscopic surgery lobectomy, tracheal resection, and sleeve resection). The participants provided critical feedback regarding the realism and utility of the simulators, which served as the basis for a composite assessment of the simulators. RESULTS: All participants acknowledged that simulation may not provide a wholly immersive experience. For small vessel anastomosis, the portable chest model is less realistic compared with the porcine model, but is valuable in teaching anastomosis mechanics. The aortic cannulation model allows multiple cannulations and can serve as a thoracic aortic surgery model. The cardiopulmonary bypass simulator provides crisis management experience. The porcine aortic valve replacement, mitral valve annuloplasty, and aortic root models are realistic and permit standardized training. The hilar dissection model is subject to variability of porcine anatomy and fragility of the vascular structures. The realistic esophageal anastomosis simulator presents various approaches to esophageal anastomosis. The exercise associated with the rigid bronchoscopy model is brief, and adding additional procedures should be considered. The tracheal resection, sleeve resection, and video-assisted thoracoscopic surgery lobectomy models are highly realistic and simulate advanced maneuvers. CONCLUSIONS: By providing the necessary tools, such as task trainers and assessment instruments, the Senior Tour may be one means to enhance simulation-based learning in cardiothoracic surgery. The Senior Tour members can provide regular programmatic evaluation and critical analyses to ensure that proposed simulators are of educational value. PMID- 22075062 TI - Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip. AB - OBJECTIVE: To assess the safety and symptomatic changes of IA injections of platelet-rich plasma (PRP) in patients with OA of the hip. METHODS: Forty patients affected by monolateral severe hip OA were included in the study. Each joint received three IA injections of PRP, which were administered once a week. The primary end point was meaningful pain relief, which was described as a reduction in pain intensity of at least 30% from baseline levels as evaluated by the WOMAC subscale at 6-months post-treatment. The visual analogue scale (VAS) and Harris hip score subscale for pain were used to verify the results. Secondary end points included changes in the level of disability of at least 30% and the percentage of positive responders, i.e. the number of patients that achieved a >30% reduction in pain and disability. RESULTS: Statistically significant reductions in VAS, WOMAC and Harris hip subscores for pain and function were reported at 7 weeks and 6 months (P < 0.05). Twenty-three (57.5%) patients reported a clinically relevant reduction of pain (45%, range 30-71%) as assessed by the WOMAC subscale. Sixteen (40%) of these patients were classified as excellent responders who showed an early pain reduction at 6-7 weeks, which was sustained at 6 months, and a parallel reduction of disability. Side effects were negligible and were limited to a sensation of heaviness in the injection site. CONCLUSIONS: This preliminary non-controlled prospective study supported the safety, tolerability and efficacy of PRP injections for pain relief and improved function in a limited number of patients with OA of the hip. PMID- 22075063 TI - Tocilizumab: a novel therapy for patients with large-vessel vasculitis. AB - OBJECTIVE: Treatment of large-vessel vasculitis (LVV) remains challenging. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose or after GC withdrawal. In addition, GCs are fraught with numerous adverse events. The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with LVV. METHODS: Four patients with active LVV (two with GCA and two with Takayasu arteritis) received monthly TCZ infusions (8 mg/kg bodyweight) for 6 consecutive months. Two patients were treatment naive, while two had relapsing disease. Disease activity and drug tolerability were assessed clinically and by laboratory tests at study entry and subsequently every month for 6 months of TCZ treatment, while an [(18)F]fluorodeoxyglucose PET (PET/CT) scan was performed before and after treatment. In addition, a semi-quantitative clinical evaluation was performed at baseline and at 3 and 6 months using the Indian Takayasu activity score and the Kerr indices. After TCZ, MTX was used as maintenance therapy. RESULTS: All patients treated with TCZ therapy had a satisfactory clinical and laboratory response, while PET/CT findings significantly improved in all cases. No serious adverse events were noted. Only one patient had a transient increase in liver enzymes. CONCLUSIONS: In this small group of patients with LVV, treatment with TCZ was effective and well tolerated. Further, larger studies are required to confirm our findings. PMID- 22075061 TI - Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery. AB - OBJECTIVE: Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations. METHODS: This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared. RESULTS: Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving aprotinin compared with tranexamic acid (P < .05). Recombinant activated factor VII use (2/34 [6%] vs 18/42 [43%]; P < .001), delayed sternal closure (12/34 [35%] vs 26/42 [62%]; P = .02), and inotropic requirements at 24 and 36 hours (P < .05) were also reduced in the aprotinin group. Median duration of mechanical ventilation was reduced compared with tranexamic acid: 2.9 days (interquartile range: 1.7-5.1 days) versus 4.2 days (2.9-5.2 days), P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents. CONCLUSIONS: Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes. PMID- 22075064 TI - Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis. AB - OBJECTIVE: Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Although the aetiology is unknown, sarcoidosis is thought to be mediated by Th1 lymphocytes. Recently, IL-17A has been implicated in granuloma formation in various diseases, including tuberculosis. Therefore, we hypothesized that Th17 cells play a role in sarcoidosis, paralleling recent findings in autoimmune diseases such as RA. The aim of our study was to investigate the role of Th17 cells in sarcoidosis. METHODS: T cells were investigated by intracellular flow cytometry and immunohistochemistry, in blood, bronchoalveolar lavages (BALs) and bronchial mucosal biopsies from a cohort of newly diagnosed sarcoidosis patients and healthy controls. RESULTS: Circulating memory CD4(+) T-cell populations of sarcoidosis patients contained significantly increased proportions of IL-17A(+) cells when compared with healthy controls. Interestingly, proportions of IL-17A/IFN-gamma and IL-17A/IL-4 double-producing cells were significantly increased in blood of sarcoidosis patients and were present in substantial numbers in BAL. In granuloma-containing, but not in non-granulomatous sarcoidosis biopsies, we found significantly increased numbers of IL-17A(+) T cells, located in and around granulomas throughout the lamina propria. IL-22(+) T cells were increased in the subepithelial layer. CONCLUSIONS: Enhanced IL-17A expression in granulomas and the presence of IL-17A(+), IL-17A(+)IFN-gamma(+) and IL-17A(+)IL-4(+)memory Th cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction or maintenance in sarcoidosis. Therefore, neutralization of IL-17A activity may be a novel strategy to treat sarcoidosis. PMID- 22075065 TI - Correlation between computer-aided dynamic gadolinium-enhanced MRI assessment of inflammation and semi-quantitative synovitis and bone marrow oedema scores of the wrist in patients with rheumatoid arthritis--a cohort study. AB - OBJECTIVE: To test the correlation between assessment of inflammation using dynamic contrast-enhanced MRI (DCE-MRI) analysed by a novel computer-aided approach and semi-quantitative scores of synovitis and bone marrow oedema (BME) using the OMERACT-RA MRI Scoring (RAMRIS) system, in the wrist of patients with RA. METHODS: Fifty-four RA patients had conventional and DCE-MRI of a symptomatic wrist using a low-field 0.2T extremity scanner. RAMRIS synovitis and BME of the wrist joint were done. DCE-MRI data were analysed in three ways: (i) in all images (fully automated approach), (ii) within a large extended region of interest (ROI) placed around the wrist joint (semi-automated approach) and (iii) within a small ROI placed in the area with most visual enhancement (semi automated approach). Time spent on each procedure was noted. Spearman's rank correlation test was applied to assess the correlation between RAMRIS and the computer-generated dynamic parameters. RESULTS: RAMRIS synovitis (range 2-9), BME (range 0-39) and the dynamic parameters reflecting the number of enhancing voxels were significantly correlated, especially when an extended ROI around the wrist was used (rho = 0.74; P < 0.01 for synovitis and rho = 0.82; P < 0.01 for BME). The observer spent on average 20 min (range 12-25 min) to perform RAMRIS, including acquisition of the results in the database, and 8 min (range 7-10 min) to perform all above-mentioned computer-aided analyses. CONCLUSION: Computer aided analysis of DCE-MRI data correlated with RAMRIS synovitis and BME and was twice as fast to perform. This technique may be useful for quick semi-automated assessment of joint inflammation, but needs further validation. PMID- 22075066 TI - Factors and comorbidities associated with first neuropsychiatric event in systemic lupus erythematosus: does a risk profile exist? A large multicentre retrospective cross-sectional study on 959 Italian patients. AB - OBJECTIVE: To analyse risk factors and comorbidities potentially associated with CNS involvement in a large cohort of Italian patients affected by SLE. METHODS: A number of generic (not strictly SLE related) and specific (disease related) risk factors to which all patients have been exposed in the span of 5 years before the first neuropsychiatric (NP) event or before the last available observation were checked for and their distribution was analysed in 959 SLE patients with and without NP involvement; all the first NP events that occurred in a time frame of 10 years were recorded and categorized as SLE related or SLE unrelated. RESULTS: Three hundred and twenty-six SLE patients with and 633 SLE patients without NP manifestations were included in the study. A total of 469 NP events were recorded. Headache (26.1%), cerebrovascular events (22.7%), mood disorders (8.9%), seizures (14.4%) and cognitive dysfunctions (9.5%) were the most frequent SLE-related NP events. More risk factors [mean 4.52 (2.44) vs 3.73 (2.01); P < 0.0001] were observed in patients with than without NP involvement. Overall, aPLs, LA and APS were factors more strongly associated with NP involvement. CONCLUSIONS: In SLE, NP involvement and aPLs were confirmed as closely related. Furthermore, other modifiable generic risk factors, such as hypertension, carotid vasculopathy and dyslipidaemia, appeared to be related to the occurrence of cerebral vascular accident (CVA) and cognitive dysfunctions, suggesting the need for a more intensive preventive strategy to optimize the management of NP lupus. PMID- 22075067 TI - The discovery of the pyramidal neurons: Vladimir Betz and a new era of neuroscience. AB - As a consequence of nascent technology, the 19th century witnessed a profound change in orientation to the nervous system. For example, improved microscopy in the first half of the 19th century allowed high magnification without blurring. The subsequent observation of nucleated cells led to the identification of individual brain cells. Philosophical changes in approach to the natural sciences took their lead from those applied to physical observations. The Ukrainian anatomist and histologist, Vladimir Alekseyevich Betz (1834-94) played a pivotal role in reshaping scientific and philosophical approaches to the brain, connecting cerebral localization, function and brain microstructure. Betz revolutionized methods of cell fixation and staining. Sometimes his efforts yielded enormously complicated technological improvements. Betz's greatest contribution, however, was connecting his discovery of the function of giant pyramidal neurons of the primary motor cortex ('cells of Betz') with the cortical organization. Considering cortical cytoarchitectonics in relation with physiological function, Betz recognized this organization in two areas: motor and sensory. He defined a functional area on histological grounds and thereby opened the way to study precise cortical areas. Betz participated in the scientific transformation of cytoarchitectonics based on macro- and microscopic studies of the cortical surface, enabling him to view the paths of nerve cells in the brain. Betz's influence allowed systemization of scattered scientific findings. The discovery of pyramidal cells was a turning point in the prevailing philosophical and scientific approach to the brain, linking cytoarchitecture, neurophysiology and cerebral localization. PMID- 22075068 TI - Believing is perceiving: mismatch between self-report and actigraphy in psychogenic tremor. AB - We assessed the duration and severity of tremor in a real-life ambulatory setting in patients with psychogenic and organic tremor by actigraphy, and compared this with self-reports of tremor over the same period. Ten participants with psychogenic tremor and eight with organic tremor, diagnosed using standardized clinical criteria, were studied. In an explicit design, participants were asked to wear a small actigraph capable of continuously monitoring tremor duration and intensity for 5 days while keeping a diary of their estimates of tremor duration during the same period. Eight patients with psychogenic tremor and all patients with organic tremor completed the study. Psychogenic patients reported significantly more of the waking day with tremor compared with patients with organic tremor (83.5 +/- 14.0% of the waking day versus 58.0 +/- 19.0% of the waking day; P < 0.01), despite having almost no tremor recorded by actigraphy (3.9 +/- 3.7% of the waking day versus 24.8 +/- 7.7% of the waking day; P = 0.001). Patients with organic tremor reported 28% more tremor than actigraphy recordings, whereas patients with psychogenic tremor reported 65% more tremor than actigraphy. These data demonstrate that patients with psychogenic tremor fail to accurately perceive that they do not have tremor most of the day. The explicit study design we employed does not support the hypothesis that these patients are malingering. We discuss how these data can be understood within models of active inference in the brain to provide a neurobiological framework for understanding the mechanism of psychogenic tremor. PMID- 22075069 TI - Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis as a system failure is a concept supported by the finding of consistent extramotor as well as motor cerebral pathology. The functional correlates of the structural changes detected using advanced magnetic resonance imaging techniques such as diffusion tensor imaging and voxel-based morphometry have not been extensively studied. A group of 25 patients with amyotrophic lateral sclerosis was compared to healthy control subjects using a multi-modal neuroimaging approach comprising T(1)-weighted, diffusion-weighted and resting-state functional magnetic resonance imaging. Using probabilistic tractography, a grey matter connection network was defined based upon the prominent corticospinal tract and corpus callosum involvement demonstrated by white matter tract-based spatial statistics. This 'amyotrophic lateral sclerosis specific' network included motor, premotor and supplementary motor cortices, pars opercularis and motor-related thalamic nuclei. A novel analysis protocol, using this disease-specific grey matter network as an input for a dual-regression analysis, was then used to assess changes in functional connectivity directly associated with this network. A spatial pattern of increased functional connectivity spanning sensorimotor, premotor, prefrontal and thalamic regions was found. A composite of structural and functional magnetic resonance imaging measures also allowed the qualitative discrimination of patients from controls. An integrated structural and functional connectivity approach therefore identified apparently dichotomous processes characterizing the amyotrophic lateral sclerosis cerebral network failure, in which there was increased functional connectivity within regions of decreased structural connectivity. Patients with slower rates of disease progression showed connectivity measures with values closer to healthy controls, raising the possibility that functional connectivity increases might not simply represent a physiological compensation to reduced structural integrity. One alternative possibility is that increased functional connectivity reflects a progressive loss of inhibitory cortical influence as part of amyotrophic lateral sclerosis pathogenesis, which might then have relevance to future therapeutic strategies. PMID- 22075070 TI - Subthalamic nucleus stimulation reverses spinal motoneuron activity in parkinsonian patients. AB - Although a cardinal symptom of Parkinsonian disease, up to now, rigidity has been investigated much less than spasticity in hemiplegic patients. Many pathophysiological mechanisms may at least theoretically contribute to Parkinsonian rigidity, from altered viscoelastic muscle properties to inability of parkinsonian patients to relax. However, as demonstrated many years ago, motoneuron responses to muscle afferent volleys are involved in rigidity since afferent volleys are suppressed after dorsal root section. To our knowledge, homosynaptic depression (i.e. the fact that motoneuron responses to Ia afferent volleys exhibit a frequency-related depression) has not been studied in parkinsonian disease, despite the fact that in spastic patients, changes in homosynaptic depression are significantly correlated at wrist and ankle levels with the severity of spasticity. Thus, in the present series of experiments, we investigated in parkinsonian patients with chronic implantation of both subthalamic motor nuclei, the amount of homosynaptic depression at wrist and ankle levels on and off deep brain stimulation. Off deep brain stimulation, the frequency-related depression disappeared, the patients became rigid and the amount of homosynaptic depression was significantly correlated with the severity of rigidity. On deep brain stimulation, the frequency-related depression was restored and the rigidity suppressed, suggesting that homosynaptic depression is one of the mechanisms underlying rigidity in Parkinson's disease. Moreover, the unexpected finding that changes in the rigidity score and the amount of homosynaptic depression are time-locked to the onset of deep brain stimulation leads us to reconsider the mechanisms underlying changes in homosynaptic depression. PMID- 22075071 TI - Critical neural substrates for correcting unexpected trajectory errors and learning from them. AB - Our proficiency at any skill is critically dependent on the ability to monitor our performance, correct errors and adapt subsequent movements so that errors are avoided in the future. In this study, we aimed to dissociate the neural substrates critical for correcting unexpected trajectory errors and learning to adapt future movements based on those errors. Twenty stroke patients with focal damage to frontal or parietal regions in the left or right brain hemispheres and 20 healthy controls performed a task in which a novel mapping between actual hand motion and its visual feedback was introduced. Only patients with frontal damage in the right hemisphere failed to correct for this discrepancy during the ongoing movement. However, these patients were able to adapt to the distortion such that their movement direction on subsequent trials improved. In contrast, only patients with parietal damage in the left hemisphere showed a clear deficit in movement adaptation, but not in online correction. Left frontal or right parietal damage did not adversely impact upon either process. Our findings thus identify, for the first time, distinct and lateralized neural substrates critical for correcting unexpected errors during ongoing movements and error-based movement adaptation. PMID- 22075072 TI - Changes in central apnea index following pediatric adenotonsillectomy. AB - OBJECTIVES: To determine if there are changes in the central apnea index (CAI) when pediatric patients undergo adenotonsillectomy for obstructive sleep apnea (OSA). STUDY DESIGN: Case series with chart review. SETTING: Two tertiary children's hospitals. SUBJECTS AND METHODS: Children between 1 and 16 years of age who underwent adenotonsillectomy for OSA and had both preoperative and postoperative full-night polysomnography (PSG) with CAI greater than 1 on preoperative PSG were eligible for inclusion. Central apnea was defined as the absence of both inspiratory effort and chest wall movement lasting longer than 20 seconds. Criteria for diagnosis of central sleep apnea (CSA) was CAI greater than 1. RESULTS: A total of 101 children with OSA had preoperative and postoperative PSG. Fifteen of these patients had a preoperative CAI greater than 1. The mean age was 67.7 months (SD, 62.7 months). The CAI ranged from 1.1 to 11.1. The mean preoperative CAI was 3.9 (SD, 2.9), while the mean postoperative CAI was 1.9 (SD, 4.8). There was significant improvement (P = .008) of the CAI following adenotonsillectomy. Ninety percent of subjects with mild CSA (CAI between 1 and 5) had postoperative resolution of their disease. There was also significant improvement (P = .004) in the obstructive apnea hypopnea index (AHI), with the mean preoperative AHI of 22.8 (SD, 19.8) decreasing to an AHI of 5.5 (SD, 6.5) postoperatively. CONCLUSIONS: Children with OSA and mild CSA on preoperative PSG showed significant improvement in CAI following adenotonsillectomy. Future studies are needed to determine the clinical significance of CSA in children with OSA and to identify treatment strategies. PMID- 22075073 TI - Surgical parathyroidectomy versus cinacalcet therapy: in the management of secondary hyperparathyroidism. AB - OBJECTIVES: The aim of this study was to compare the clinical effectiveness of surgery with calcimimetics as treatment strategies for managing the biochemical abnormalities that characterize secondary hyperparathyroidism (2HPTH), resistant to optimal conventional therapy in patients with end-stage renal failure (ESRF). STUDY DESIGN: A historical cohort study. SETTING: Maxillofacial Department, Morriston Hospital, Swansea, United Kingdom. SUBJECTS AND METHODS: Fifty-four patients with 2HPTH resistant to optimal conventional medical management were studied. One cohort of 20 patients was treated with surgical parathyroidectomy, the other cohort of 34 patients with cinacalcet. Serum parathyroid hormone (PTH) and bone profile were measured before and at monthly intervals after intervention. RESULTS: Both cohorts were comparable in their demographic profile, pretreatment comorbidities, baseline PTH, and bone profile. In all 20 surgical patients, the 1-week postoperative PTH had decreased by 97% (P < .001); in the medical cohort after 4 months of daily cinacalcet, the PTH decreased by 48% (P < .001) from baseline. This reduction was maintained at 18 months. In all but 1 surgical patient, alkaline phosphatase (ALP) decreased to normal levels, whereas on cinacalcet, there was no statistically significant reduction. Patients who underwent parathyroidectomy had a more significant decrease in PTH (P < .001) and ALP (P < .0014) than did patients on cinacalcet therapy. All patients managed surgically who complained of preoperative symptoms of pruritis and bone pain expressed complete resolution or significant improvement after parathyroidectomy (P < .001, P < .003, respectively). CONCLUSION: Surgery was superior to "medical" parathyroidectomy in controlling PTH and ALP. PMID- 22075074 TI - Factors correlating with burnout in practicing otolaryngologists. AB - OBJECTIVE: This study sought to determine which demographic and practice characteristics were predictive of professional burnout in otolaryngologists. STUDY DESIGN: Cross-sectional survey. SETTING: Tertiary care hospital. SUBJECTS AND METHODS: Postal mailings, including the Maslach Burnout Inventory (MBI), were sent to alumni of the University of Iowa Hospitals and Clinics otolaryngology program. Participants completed the MBI according to the enclosed instructions. In addition, they answered a brief questionnaire comprising 8 items designed to collect demographic information. The MBI was then scored and subjects were classified according to their degree of burnout. Statistical analysis was then performed, and correlations were used to summarize associations between continuous variables. RESULTS: This study had a response rate of 49% to the survey. Of the respondents, 3.5% met criteria for burnout syndrome, and 16% were classified as having high levels of burnout according to the MBI. Young age, number of hours worked per week, and length of time in practice were found to be statistically significant predictors of burnout. In addition, the length of time married and the presence of children in the home were also significant predictors of burnout. CONCLUSION: The authors report an investigation of burnout in practicing otolaryngologists using a validated instrument with correlation to potentially modifiable risk factors. The experience of burnout was found to correlate significantly with both personal and professional factors, each of which can potentially be addressed to curb the incidence of burnout. Further understanding of the potential risk factors for burnout is necessary to minimize and prevent burnout among practicing otolaryngologists. PMID- 22075075 TI - Novel approach of medialization thyroplasty with arytenoid adduction performed under general anesthesia with a laryngeal mask. AB - OBJECTIVE: To objectively assess the voice outcomes of patients with unilateral vocal fold paralysis treated with medialization thyroplasty and arytenoid adduction suture. STUDY DESIGN: Case series of patients who underwent medialization thyroplasty and arytenoid adduction suture. Preoperative and postoperative voice testing was performed and the data were compared by statistical analysis. SETTING: Tertiary referral teaching hospital in Sydney, Australia. SUBJECTS: All patients had a unilateral vocal fold paralysis, with a large posterior glottic gap and vocal symptoms affecting their quality of life. METHODS: Thirteen patients with a diagnosis of a unilateral vocal fold paralysis with a large posterior glottic gap, vocal symptoms, and total denervation of the vocal fold underwent medialization thyroplasty and arytenoid adduction suture. The surgery was performed in a novel method under a general anesthetic using a laryngeal mask and with direct intraoperative endoscopic feedback. Preoperative and postoperative measures of voice performance were compared, including acoustic analysis (fundamental frequency, speech intensity against quiet and loud background noise, speech rate) and aerodynamic assessment (airflow, maximum phonation time). RESULTS: Medialization thyroplasty with arytenoid adduction suture significantly improved aerodynamic assessment and phonation duration for both male and female subjects overall. There were 2 of 13 treatment failures. Median follow-up time was 6 months. CONCLUSION: Preliminary results indicate that in selected patients with vocal fold paralysis, medialization thyroplasty with arytenoid adduction suture leads to significant improvements in objective voice measures. Longer follow-up data are required to further quantify the voice outcomes after this procedure. PMID- 22075076 TI - Three-year ear, nose, and throat cross-sectional analysis of audiometric protocols for magnetic resonance imaging screening of acoustic tumors. AB - OBJECTIVES: (1) Evaluate audiometric protocols and recommend protocols with best sensitivity and specificity for magnetic resonance imaging (MRI) screening of acoustic tumors; (2) determine clinical risks (false negative) of missing acoustic tumors and potential wastes in screening (false positive) nonacoustic tumors or radiologically "normal" cases; and (3) identify the decibel difference and range of frequencies compared by the best-performing protocols. STUDY DESIGN: Cross-sectional study with chart review. SETTING: Ear, nose, and throat (ENT); audiology; and radiology departments in a tertiary-care hospital. SUBJECTS AND METHODS: Three-year cohort (2006-2009) of 1751 ENT patients underwent MRI screening and pure-tone audiometry indicating sensorineural hearing loss. Audiometric protocols were ranked by highest sensitivity to acoustic tumors, specificity A to nonacoustic tumors, and specificity B to "radiologically normal" cases. RESULTS: No audiometric protocols achieved 100% sensitivity or specificity rates. Only 2 protocols achieved >=90% sensitivity: the AMCLASS-A-Urben protocol (93.16%) and the Mangham protocol (91.58%). Eleven of 15 protocols for specificity A and 12 of 15 protocols for specificity B achieved >=50%. Clinical risks ranged from 6.84% to 18.95%, whereas potential wastes ranged from 33.56% to 68.37% for specificity A and 31.76% to 66.86% for specificity B. Interaural difference parameters indicating highest mean sensitivity were on the order of >=10 dB, >=15 dB, and >=20 dB. For frequency comparison parameters, "2 or more adjacent frequency" and "single-frequency" comparison indicated higher mean sensitivity than the "averaged multifrequency" comparison. Mean specificity showed an opposite pattern. CONCLUSIONS: For optimum sensitivity, the Mangham protocol is preferred (sensitivity, 91.58%; specificity A, 44.23%; specificity B, 44.91%), which proposes a >=10-dB interaural difference, averaging 1 to 8 kHz. For optimum specificity, the American Academy of Otolaryngology-Head and Neck Surgery protocol is preferred (sensitivity, 87.37%; specificity A, 65.38%; specificity B, 66.04%), which proposes >=15 dB between ears, averaging 0.5 to 3 kHz. PMID- 22075077 TI - Analysis of swallowing function after supracricoid laryngectomy with cricohyoidopexy. AB - OBJECTIVE: To evaluate the swallowing function after supracricoid laryngectomy with cricohyoidopexy, focusing on the effects of arytenoid cartilage resection and radiation therapy. STUDY DESIGN: Case series with chart review. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Thirty supracricoid laryngectomy cricohyoidopexy patients, at least 1 year after treatment, were retrospectively analyzed. Fiber-optic endoscopic evaluation of swallowing was performed for each patient. Three blinded judges evaluated the video recordings based on 3 parameters. The M. D. Anderson Dysphagia Inventory was completed by each patient for assessment of disease-specific quality of life. RESULTS: All patients were decannulated at an average of 23.6 days. Nasogastric feeding tubes were removed at an average of 27.3 days, and all patients could eat orally. Fiber-optic endoscopic evaluation of swallowing showed that patients with total resection of 1 arytenoid had more bolus retention than patients with both arytenoids preserved (P = .008). Compared with patients who did not receive radiotherapy, patients who did receive radiotherapy exhibited increased retention (P = .021) and aspiration (P = .007). The M. D. Anderson Dysphagia Inventory results revealed no differences in quality of life according to the level of arytenoid resection or the administration of radiotherapy. CONCLUSION: The functional evaluation of swallowing after supracricoid laryngectomy-cricohyoidopexy showed satisfactory results. Patients with total resection of 1 arytenoid had significantly higher bolus retention, and those who received radiotherapy had significantly increased retention and aspiration. PMID- 22075078 TI - Contemporary assessment of medical morbidity and mortality in head and neck surgery. AB - OBJECTIVE: To update the incidence of medical morbidity and mortality in head and neck surgery and factors that influence length of stay (LOS). STUDY DESIGN: Cross sectional analysis of a national database. SETTING: Academic medical center. METHODS: A specific database for head and neck surgical procedures was extracted from the National Hospital Data Survey for 2005 through 2007. Records of inpatient admissions for patients undergoing head and neck surgery as the primary procedure were examined to establish the frequency of medical complications, mortality, and LOS. The association of these medical complications with mortality and LOS was determined. RESULTS: A total of 330,629 head and neck procedures were analyzed. The overall medical morbidity and mortality rates were 5.0% +/- 0.7% and 0.4% +/- 0.2%, respectively. The most common medical complication was hospital-acquired pneumonia (3.3% +/- 0.6%), whereas acute renal failure, stroke, acute myocardial infarction, pulmonary embolism, and deep venous thrombosis were substantially less frequent (combined incidence, 2.1%). The mean LOS for patients without a major complication was 3.3 +/- 0.2 days vs 14.0 +/- 1.9 days for those with a major complication (P < .001). CONCLUSIONS: Medical morbidity and mortality in patients undergoing head and neck surgical procedures continue to be exceedingly low. Although medical complications are associated with a longer LOS, the influence of medical complications on mortality has declined. Enhancements in perioperative medical management of head and neck surgical patients are likely responsible for these improved results. PMID- 22075079 TI - Chromosomal mapping of rDNAs and H3 histone sequences in the grasshopper rhammatocerus brasiliensis (acrididae, gomphocerinae): extensive chromosomal dispersion and co-localization of 5S rDNA/H3 histone clusters in the A complement and B chromosome. AB - BACKGROUND: Supernumerary B chromosomes occur in addition to standard karyotype and have been described in about 15% of eukaryotes, being the repetitive DNAs the major component of these chromosomes, including in some cases the presence of multigene families. To advance in the understanding of chromosomal organization of multigene families and B chromosome structure and evolution, the distribution of rRNA and H3 histone genes were analyzed in the standard karyotype and B chromosome of three populations of the grasshopper Rhammatocerus brasiliensis. RESULTS: The location of major rDNA was coincident with the previous analysis for this species. On the other hand, the 5S rDNA mapped in almost all chromosomes of the standard complement (except in the pair 11) and in the B chromosome, showing a distinct result from other populations previously analyzed. Besides the spreading of 5S rDNA in the genome of R. brasiliensis it was also observed multiple sites for H3 histone genes, being located in the same chromosomal regions of 5S rDNAs, including the presence of the H3 gene in the B chromosome. CONCLUSIONS: Due to the intense spreading of 5S rRNA and H3 histone genes in the genome of R. brasiliensis, their chromosomal distribution was not informative in the clarification of the origin of B elements. Our results indicate a linked organization for the 5S rRNA and H3 histone multigene families investigated in R. brasiliensis, reinforcing previous data concerning the association of both genes in some insect groups. The present findings contribute to understanding the organization/evolution of multigene families in the insect genomes. PMID- 22075080 TI - Interprofessional education for the quality use of medicines: designing authentic multimedia learning resources. AB - It is claimed that health care students who learn together will be better prepared for contemporary practice and more able to work collaboratively and communicate effectively. In Australia, although recognised as important for preparing nursing, pharmacy and medical students for their roles in the medication team, interprofessional education is seldom used for teaching medication safety. This is despite evidence indicating that inadequate communication between health care professionals is the primary issue in the majority of medication errors. It is suggested that the pragmatic constraints inherent in university timetables, curricula and contexts limit opportunities for health professional students to learn collaboratively. Thus, there is a need for innovative approaches that will allow nursing, medical and pharmacy students to learn about and from other disciplines even when they do not have the opportunity to learn with them. This paper describes the development of authentic multimedia resources that allow for participative, interactive and engaging learning experiences based upon sound pedagogical principles. These resources provide opportunities for students to critically examine clinical scenarios where medication safety is, or has the potential to be compromised and to develop skills in interprofessional communication that will prepare them to manage these types of situations in clinical practice. PMID- 22075081 TI - In vitro and in vivo characterization of AS2643361, a novel and highly potent inosine 5'-monophosphate dehydrogenase inhibitor. AB - Inosine 5'-monophosphate (IMP) dehydrogenase is a critical target in solid organ transplantation. To this end, the development of mycophenolate mofetil (MMF) represents a major advance in transplant medicine. Here, we investigated the in vitro and in vivo pharmacological effects of a novel IMP dehydrogenase inhibitor, AS2643361, in several immunological and non-immunological models. The in vitro inhibitory activity of AS2643361 on immune cell and endothelial cell proliferation and on antibody production from lipopolysaccharide-stimulated B cells, was significantly more potent than that of mycophenolic acid, the active form of MMF, despite the similar potency of these compounds on IMP dehydrogenase. In a rat heterotopic cardiac transplant model, monotherapy using orally administered AS2643361 at 10 or 20mg/kg/day prolonged the median graft survival time from 6 to 16 and 19days, respectively. In dinitrophenol-lipopolysaccharide stimulated rats, oral administration of AS2643361 at 2.5, 5 or 10mg/kg/day resulted in suppression of antibody production. In vivo antibody production against alloantigen was also suppressed by AS2643361 treatment at 5 or 10mg/kg/day. Furthermore, treatment with AS2543361 effectively inhibited balloon injury induced-intimal thickening, which is a major cause of late allograft loss. Overall, the in vivo activity of AS2643361 was over two-fold more potent than that of MMF. In addition, gastrointestinal toxicity, considered a dose-limiting factor for MMF, was reduced with AS2643361 treatment. These results suggest AS2643361 has higher potency and less toxicity than MMF, making it a potential candidate for treatment of acute and chronic rejection in transplant medicine. PMID- 22075082 TI - Modulation of synaptic plasticity in the hippocampus by hippocampus-derived estrogen and androgen. AB - The hippocampus synthesizes estrogen and androgen in addition to the circulating sex steroids. Synaptic modulation by hippocampus-derived estrogen or androgen is essential to maintain healthy memory processes. Rapid actions (1-2h) of 17beta estradiol (17beta-E2) occur via synapse-localized receptors (ERalpha or ERbeta), while slow genomic E2 actions (6-48h) occur via classical nuclear receptors (ERalpha or ERbeta). The long-term potentiation (LTP), induced by strong tetanus or theta-burst stimulation, is not further enhanced by E2 perfusion in adult rats. Interestingly, E2 perfusion can rescue corticosterone (stress hormone) induced suppression of LTP. The long-term depression is modulated rapidly by E2 perfusion. Elevation of the E2 concentration changes rapidly the density and head structure of spines in neurons. ERalpha, but not ERbeta, drives this enhancement of spinogenesis. Kinase networks are involved downstream of ERalpha. Testosterone (T) or dihydrotestosterone (DHT) also rapidly modulates spinogenesis. Newly developed Spiso-3D mathematical analysis is used to distinguish these complex effects by sex steroids and kinases. It has been doubted that the level of hippocampus-derived estrogen and androgen may not be high enough to modulate synaptic plasticity. Determination of the accurate concentration of E2, T or DHT in the hippocampus is enabled by mass-spectrometric analysis in combination with new steroid-derivatization methods. The E2 level in the hippocampus is approximately 8nM for the male and 0.5-2nM for the female, which is much higher than that in circulation. The level of T and DHT is also higher than that in circulation. Taken together, hippocampus-derived E2, T, and DHT play a major role in modulation of synaptic plasticity. PMID- 22075084 TI - Transmission of a live Eimeria acervulina vaccine strain and response to infection in vaccinated and contact-vaccinated broilers. AB - Live vaccines for coccidiosis control are infrequently used in broilers, mainly due to variability in efficacy and relatively high costs. More insight in transmission of vaccine and wild-type strains can facilitate optimization of vaccination strategies and might increase its use as an alternative for anticoccidial drugs. The aim of this study was to quantify transmission of a live Eimeria acervulina vaccine strain and to determine the degree of protection against a subsequent infection with a wild-type E. acervulina strain. An experiment was carried out with 4 groups of 22 SPF broilers. At 2 days of age, 11 birds of groups 2 to 4 were vaccinated directly by oral application of E. acervulina oocysts of the ParacoxTM vaccine and 11 birds were placed in contact with these birds (contact-vaccinated). Birds in group 1 remained unvaccinated (controls) and were not exposed to vaccinated birds. At day 28 of age, 6 groups of 10 birds were formed, with 2 groups (duplo) for each treatment group, i.e. vaccinated, contact-vaccinated or unvaccinated control birds. Five birds of each group were orally inoculated with wild-type E. acervulina oocysts and five were contact-exposed. Single droppings were examined daily from days 5 to 49 of age for oocyst output and to determine the time of infection. The transmission rate of the vaccine strain was estimated to be 1.6 per day and of the wild-type strain 2.3, 8.7 and 20.8 per day for vaccinated, contact-vaccinated and unvaccinated birds, respectively. Although transmission of wild-type coccidia was not significantly reduced in vaccinated or contact-vaccinated groups, both groups were equally protected against high oocyst output after infection compared to unvaccinated groups. These results suggest that factors influencing transmission of live vaccine strains in flocks may be important targets for improvement of vaccine efficacy and warrant further research. PMID- 22075083 TI - Nebulized live-attenuated influenza vaccine provides protection in ferrets at a reduced dose. AB - Live-attenuated influenza vaccine (LAIV) is delivered to vaccine recipients using a nasal spray syringe. LAIV delivered by this method is immunogenic at current doses; however, improvements in nasal delivery might allow for significant dose reduction. We investigated LAIV vaccination in ferrets using a high efficiency nebulizer designed for nasal delivery. LAIV nasal aerosol elicited high levels of serum neutralizing antibodies and protected ferrets from homologous virus challenge at conventional (10(7)TCID(50)) and significantly reduced (10(3)TCID(50)) doses. Aerosol LAIV also provided a significant level of subtype specific cross-protection. These results demonstrate the dose-sparing potential of nebulizer-based nasal aerosol LAIV delivery. PMID- 22075085 TI - Survey of national immunization programs and vaccine coverage rates in Asia Pacific countries. AB - Children in the Asia Pacific region are still suffering from certain vaccine preventable diseases. The current study surveyed the national immunization programs and vaccine uptake of traditional and newly developed vaccines in 12 countries in this area. The results showed children in most countries were well protected from conventional vaccine-preventable diseases, while immunization programs for certain diseases such as poliovirus or measles should be strengthened in certain countries. Protection against pneumococcus, rotavirus, and human papillomavirus infections were obviously inadequate in most of the countries in the region. Promoting coverage of newly developed vaccines will benefit a great number of children in this area. PMID- 22075086 TI - Antigen dose escalation study of a VEGF-based therapeutic cancer vaccine in non human primates. AB - CIGB-247 is a cancer therapeutic, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the oil free adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). Our previous experimental studies in mice with CIGB-247 have shown that the vaccine has both anti-tumoral and anti-metastatic activity, and produces both antibodies that block VEGF-VEGF receptor interaction, and a specific T-cell cytotoxic response against tumor cells. CIGB-247, with an antigen dose of 100 MUg, has been characterized by an excellent safety profile in mice, rats, rabbits, and non human primates. In this article we extend the immunogenicity and safety studies of CIGB-247 in non human primates, scaling the antigen dose from 100 MUg to 200 and 400 MUg/vaccination. Our results indicate that such dose escalation did not affect animal behavior, clinical status, and blood parameters and biochemistry. Also, vaccination did not interfere with skin deep skin wound healing. Anti-VEGF IgG antibodies and specific T-cell mediated responses were documented at all three studied doses. Antigen dose apparently did not determine differences in maximum antibody titer during the 8 weekly immunization induction phase, or the subsequent increase in antibodies seen for monthly boosters delivered afterwards. Higher antigen doses had a positive influence in antibody titer maintenance, after cessation of immunizations. Boosters were important to achieve maximum antibody VEGF blocking activity, and specific T-cell responses in all individuals. Purified IgG from CIGB-247 immunized monkey sera was able to impair proliferation and formation of capillary-like structures in Matrigel, for HMEC cells in culture. Altogether, these results support the further clinical development of the CIGB-247 therapeutic cancer vaccine, and inform on the potential mechanisms involved in its effect. PMID- 22075087 TI - Correlation between serum bactericidal activity against Neisseria meningitidis serogroups A, C, W-135 and Y measured using human versus rabbit serum as the complement source. AB - The surrogate of protection against invasive meningococcal disease is the presence of serum bactericidal activity (SBA) at a titer >=4 in an assay using human serum as the complement source (hSBA). However, for various practical and logistical reasons, many meningococcal vaccines in use today were licensed based on a modified SBA assay that used baby rabbit serum as the complement source (rSBA). To assess the strength of correlation between the two assay systems for serogroups A, C, W-135 and Y, we analyzed a subset of samples from adolescent subjects enrolled in a Phase II study of Novartis' MenACWY-CRM conjugate vaccine vs. an ACWY polysaccharide vaccine; samples were analyzed in parallel using hSBA and rSBA. We compared geometric mean titers (GMTs), calculated Pearson correlation coefficients between paired hSBA and rSBA results, and calculated sensitivity/specificity and likelihood ratios for an rSBA >=8 or >=128 for classifying hSBA >=4, taking hSBA as the 'gold standard'. Correlations between hSBA and rSBA ranged from 0.46 to 0.78 for serogroup C, but were weaker for serogroups A, W-135 and Y (range -0.15 to 0.57). In post vaccination samples, nearly all subjects had rSBA titers >=8, though up to 15% remained seronegative by hSBA. In post vaccination settings, rSBA titers at >=8 or >=128 was highly sensitive for an hSBA titer >=4, but non-specific. In conclusion, results generated by rSBA did not accurately classify serostatus according to hSBA for serogroups A, W-135 and Y. PMID- 22075088 TI - Effect of age and frequency of injections on immune response to hepatitis B vaccination in drug users. AB - Despite the high immunogenicity of the hepatitis B vaccine, evidence suggests that immunological response in drug users is impaired compared to the general population. A sample of not-in-treatment adult drug users from two communities in Houston, TX, USA, susceptible to hepatitis B virus (HBV), was sampled via outreach workers and referral methodology. Participants were randomized to either the standard multi-dose hepatitis B vaccine schedule (0, 1, and 6 months) or to an accelerated (0, 1, and 2 months) schedule. The participants were followed for 1 year. Antibody levels were measured at 2, 6 and 12 months after enrollment in order to determine the immune responses. At 12 months, cumulative adequate protective response was achieved in 65% of the HBV susceptible subgroup using both the standard and accelerated schedules. The standard group had a higher mean antibody titer (184.6 mIU/mL vs 57.6 mIU/mL). But at 6 months, seroconversion at the adequate protective response was reached by a higher proportion of participants and the mean antibody titer was also higher in the accelerated schedule group (104.8 mIU/mL vs. 64.3 mIU/mL). Multivariate analyses indicated a 63% increased risk of non-response for participants 40 years or older (p=0.046). Injecting drugs more than once a day was also highly associated with the risk of non-response (p=0.016). Conclusions from this research will guide the development of future vaccination programs that anticipate other prevalent chronic conditions, susceptibilities, and risk-taking behaviors of hard-to-reach populations. PMID- 22075089 TI - Comparison of immune responses and protective efficacy of intranasal prime-boost immunization regimens using adenovirus-based and CpG/HH2 adjuvanted-subunit vaccines against genital Chlamydia muridarum infection. AB - An efficacious Chlamydia vaccine is urgently needed to control Chlamydia infections. Heterologous prime-boost vaccination regimens are emerging as a promising strategy for preventing intracellular viral and bacterial infections. However, it remains to be determined if this regimen would be a feasible and effective approach for Chlamydia infection. In this study, we examined the immune response and the protective efficacy induced by various vaccination regimens using a recombinant adenovirus vector expressing the Chlamydia antigen CPAF (AdCPAF) and recombinant CPAF (rCPAF) subunit vaccines formulated with CpG oligodeoxynucleotides and/or a synthetic immunomodulatory peptide HH2 as adjuvants. A single dose of AdCPAF stimulated potent antibody production but weak cellular immune responses in mice. A booster rCPAF vaccine formulated with both CpG and HH2, but not CpG alone or HH2 alone, showed robust adjuvant effects on induction of Th1-biased cellular immune responses in mice primed with AdCPAF. In contrast, a homologous regimen using rCPAF/CpG/HH2 subunit vaccine for both priming and boosting induced a weak antibody response, but potent cellular immunity with a mixed Th1/Th17 profile. Despite the disparities observed in humoral and cellular immune responses, both the heterologous and homologous prime boost regimens conferred significant immune protection against genital Chlamydia muridarum challenge in C3H/HeN and BALB/c mice. PMID- 22075090 TI - Effectiveness of mouse brain-derived inactivated Japanese encephalitis vaccine in Thai National Immunization Program: a case-control study. AB - Mouse brain-derived, purified inactivated Japanese encephalitis vaccine (MB JEV) has been locally produced and introduced into Thai National Immunization Program (NIP) since 1990. However, MB JEV effectiveness has been concerned, since 30-40% of JE cases received JE vaccines were recently reported in two descriptive studies. Therefore, in 2010, a case-control study was designed to assess effectiveness of the MB JEV used in the NIP, among children aged 1 to <6 years. Subjects enrolled from all regions of the country, 26 cases were clinical encephalitis with laboratory-confirmed for JE IgM titer, while 103 controls had past illness free on encephalitis. For each case, four controls were enrolled from children living in the same community with the case. Individual health records of the subjects were used to verify JE immunization status. Among children aged >= 18 months old, the recommended age by the NIP, the effectiveness was estimated at 94.6% (95%CI, 79.6-98.6%) and adjusted effectiveness was 97.50% (95%CI, 88.60-99.50%). The study results suggest that the MB JEV used in the NIP is highly effective, even among children aged <18 months. Therefore, aggressive immunization using the MB JEV would greatly diminish disease burden. PMID- 22075091 TI - Time for change? An economic evaluation of integrated cervical screening and HPV immunization programs in Canada. AB - Many jurisdictions have implemented universal human papillomavirus (HPV) immunization programs in preadolescent females. However, the cost-effectiveness of modified cervical screening guidelines and/or catch-up immunization in older females in Canada has not been evaluated. We conducted a cost-utility analysis of screening and immunization with the bivalent vaccine for the Canadian setting from the Ministry of Health perspective. We used a dynamic model to capture herd immunity and included cross-protection against strains not included in the vaccine. We found that adding catch-up immunization to the current program would be cost-effective, and that combining catch-up immunization with delaying the age at which screening is first initiated could result in cost savings and net health gains. PMID- 22075092 TI - Vaccination and risk of type 1 diabetes mellitus in active component U.S. Military, 2002-2008. AB - AIMS/HYPOTHESIS: To evaluate whether vaccination increases the risk of type 1 diabetes mellitus in active component U.S. military personnel. METHODS: We conducted a retrospective cohort study among active component U.S. military personnel age 17-35 years. Individuals with first time diagnoses of type 1 diabetes between January 1, 2002 and December 31, 2008 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We used Poisson regression to estimate risk ratios between individual vaccine exposures and type 1 diabetes. Secondary analyses were performed controlling for receipt of multiple vaccines and available demographic variables. RESULTS: Our study population consisted of 2,385,102 individuals followed for approximately 7,644,098 person-years of service. This included 1074 incident type 1 diabetes cases. We observed no significant increased risk of type 1 diabetes after vaccination with anthrax vaccine adsorbed (AVA) [RR=1.00; 95% CI (0.85, 1.17)], smallpox vaccine [RR=0.84; 95% (CI 0.70, 1.01)], typhoid vaccine [RR=1.03; 95% CI (0.87, 1.22)], hepatitis B vaccine [RR=0.83; 95% CI (0.72, 0.95)], measles mumps rubella vaccine (MMR) [RR=0.71, 95% CI (0.61, 0.83)], or yellow fever vaccine [RR=0.70; 95% CI (0.59, 0.82)]. CONCLUSIONS: We did not find an increased risk of diagnosed type 1 diabetes and any of the study vaccines. We recommend that follow-up studies using medical record review to confirm case status should be considered to corroborate these findings. PMID- 22075093 TI - The cationic lipid, diC14 amidine, extends the adjuvant properties of aluminum salts through a TLR-4- and caspase-1-independent mechanism. AB - Adjuvant efficiency is critical for inducing a protective and long-lasting immune response against weak immunogenic antigens. Discovered more than 70 years ago, aluminum salts remain the most widely used adjuvant in human vaccine. Prone to induce a strong humoral response, alum fails to drive a cell-mediated immunity, which is essential to fight against intracellular pathogens. Adjuvant systems that contain more than one component may represent an excellent alternative for completing the lack of T cell immunity associated with the injection of alum based vaccine. In this work, we demonstrated that the adjuvant effects of alum strongly benefited from combining with a cationic lipid, the diC14 amidine. Indeed, we measured a significant improvement of alum-driven IL-1beta release when human macrophages were co-cultured with a mixed suspension of alum and the diC14 amidine. Morphological analysis suggested that diC14 amidine improved the alum uptake by phagocytes. Furthermore, the addition of diC14 amidine to alum efficiently enhanced antigen processing and cross-presentation by antigen presenting cells. The biological relevance of these in vitro data was assessed by measuring the in vivo development of a cytotoxic activity and the enhanced synthesis of antigen-specific immunoglobulins after immunization with alum combined to diC14 amidine. Mechanistically, we demonstrated that diC14 amidine supported the alum adjuvanticity independently of the TLR-4 and caspase-1 agonist activities of the cationic lipid. Based on our findings, we conclude that diC14 amidine works synergistically with alum to achieve higher immune protection after vaccination. PMID- 22075094 TI - Unusual presentation of pneumocystis pneumonia in an immunocompetent patient diagnosed by open lung biopsy. AB - Pneumocystis pneumonia (PCP) is the most common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients. It is a fungal infection with Pneumocystis jiroveci which can be isolated from bronchoalveolar lavage of healthy subjects. The infection occurs mainly in HIV patients; with CD4 lymphocyte count drop to less than 200 cells/MUL. PCP has been reported in non HIV patients with other risk factors such as immunosuppressive medications, malignancies, and other inflammatory conditions. PCP has been rarely reported in immunocompetent subjects. However, in most of these patients, PCP occurred after a period of acute illness with bacterial pneumonia and antibiotic therapy. In this report, we describe a case of PCP in an immunocompetent patient with nonreactive HIV and no immunosuppressive risk factors. The patient had large pulmonary nodules discovered incidentally on chest film as preoperative evaluation for hip surgery. Bronchoalveolar lavage, transbronchial biopsies (TBB), and computed tomography (CT) guided needle biopsy were all negative for P. jiroveci. PCP diagnosis was made after open lung biopsy and wedge resection. To our knowledge, this is the first case of PCP in immunocompetent patient with negative BAL, TBB and CT guided biopsy. The diagnosis of PCP required open lung biopsy and the patient recovered without complications. PMID- 22075095 TI - The recovery of latent text from thermal paper using a simple iodine treatment procedure. AB - Faded, or actively removed text on thermally printed paper samples may be enhanced and retrieved through the use of a simple iodine fuming procedure. The recovery of printed documentation evidence in this fashion is neither affected by prior fingerprint enhancement techniques (such as ninhydrin or DFO), nor by sample age. This method allows, for the first time, evidence to be obtained from completely faded thermal paper samples (receipts, for example) as well as allowing deliberately removed printed text (a consequence of solvent washing pre treatment in latent fingerprint enhancement procedures) to be recovered. PMID- 22075096 TI - Validation of LUCIO-Direct-ELISA kits for the detection of drugs of abuse in urine: application to the new German driving licence re-granting guidelines. AB - LUCIO-Direct-enzyme linked immunosorbent assay (ELISA) tests were validated for the screening of drugs of abuse cannabis, opiates, amphetamines and cocaine in urine for the new German medical and psychological assessment (MPA) guidelines with subsequent gas chromatographic-mass spectrometric (GC-MS) confirmation. The screening cut-offs corresponding to 10 ng/mL 11-nor-delta-9-tetrahydrocannabinol 9-carboxylic acid (THC-COOH), 50 ng/mL amphetamine, 25 ng/mL morphine and codeine and 30 ng/mL benzoylecgonine were chosen at the point where the number of false negatives was lower than 1%. Due to their accuracy, ease of use and rapid analysis, these ELISA tests are very promising for cases where a large proportion of the tests are expected to be negative such as for abstinence monitoring as part of the driving licence re-granting process. PMID- 22075097 TI - International consensus group on depression prevention in bipolar disorder. PMID- 22075098 TI - Effect of antidepressant medication treatment on suicidal ideation and behavior in a randomized trial: an exploratory report from the Combining Medications to Enhance Depression Outcomes Study. AB - OBJECTIVE: To explore relationships between baseline sociodemographic and clinical features and baseline suicidal ideation, and treatment effects on suicidal ideation and behavior, in depressed outpatients. METHOD: From March 2008 to September 2009, the Combining Medications to Enhance Depression Outcomes study, a single-blind, 7-month randomized trial, enrolled outpatients with nonpsychotic chronic and/or recurrent major depressive disorder (DSM-IV-TR criteria) in primary and psychiatric care (N = 665). Participants received escitalopram plus placebo, bupropion sustained release (SR) plus escitalopram, or venlafaxine extended release (XR) plus mirtazapine. The primary outcome measure for this report is presence of suicidal ideation assessed by the Concise Health Risk Tracking Self-Report, which measures suicidal ideation and behaviors over the last 24 hours. Sociodemographic and clinical features were compared in those with versus without baseline ideation. At 4, 12, and 28 weeks, treatment effects on suicidality were assessed, and unadjusted and adjusted outcomes were compared among those with and without baseline ideation using linear, logistic, ordinal logistic, and negative binomial regression models. RESULTS: Baseline suicidal ideation was associated with greater depressive severity, childhood neglect, childhood abuse, early major depressive disorder onset, greater psychiatric comorbidity, and worse functioning and quality of life. After adjustment for treatment, gender, age at first depressive episode, obsessive-compulsive symptoms, and depressive severity, depressive symptom outcomes did not differ between ideation groups at 12 or 28 weeks or between treatments. Overall, 79% of participants with baseline suicidal ideation had none at week 4, 83% had none at week 12, and 86% had none at week 28. All treatments reduced ideation, with bupropion-SR plus escitalopram the most effective at week 12 (P < .01). In participants without baseline ideation, emergent ideation did not differ between treatments: 2.5% had ideation at 4 weeks, 1.3% had ideation at 12 weeks, and only 1.7% had ideation at 28 weeks. Four patients (all receiving venlafaxine-XR plus mirtazapine) attempted suicide (P = .0162). CONCLUSION: Baseline ideation did not affect depressive symptom outcome. Bupropion-SR plus escitalopram most effectively reduced ideation. Ideation emergence was uncommon. Venlafaxine-XR plus mirtazapine may pose a higher risk of suicide attempts. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00590863. PMID- 22075099 TI - Dimensional diagnosis and DSM-5. PMID- 22075100 TI - The problematic DSM-5 personality disorders proposal: options for plan B. PMID- 22075101 TI - Another point of view: superiority, noninferiority, and the role of active comparators. AB - Despite substantial agreement with points made by Andrew C. Leon, PhD, in his article, I am not in complete agreement in a few areas. The definition of noninferiority proposed by Leon allows drugs somewhat less effective than placebo to be characterized as noninferior to placebo, and 2 active drugs may each be simultaneously noninferior to the other. Moreover, including a placebo arm in comparing 2 active drugs is of no use in deciding whether the study is well designed or not, since a significant difference between one of the active arms and the placebo may be due to chance or to a bias in the design. An alternative view of the situation is presented. PMID- 22075102 TI - Suicide and prescription rates of intranasal corticosteroids and nonsedating antihistamines for allergic rhinitis: an ecological study. AB - OBJECTIVE: To estimate the relationship between antiallergy drug prescription rates and suicide across the United States and over time. The relationship between allergy, allergens, and suicidal behavior and suggestions of a possible immune mediation led us to hypothesize that intranasal corticosteroids, known to reduce local airway production of T-helper cell type 2 cytokines, may be associated with reduced risk of suicide relative to antihistamines, which only secondarily affect cytokine production. METHOD: The authors evaluated the relationship of suicide rates at the county level in the United States (N = 120,076 suicides) with prescriptions for intranasal corticosteroids and nonsedating antihistamines, in interaction with antidepressant prescriptions and other socioeconomic variables, for the period from 1999 to 2002. Suicide rate data were derived from state vital record systems based on local death certificate registries, and county-level allergy and antidepressant prescription data were obtained from IMS Health Incorporated (Plymouth Meeting, Pennsylvania). RESULTS: The prescription volume of intranasal corticosteroids was associated with a lower suicide risk (P = .0004), while that of antihistamines was associated with a modestly greater suicide risk (P = .0001). Adjustment for antidepressant prescriptions did not affect these relationships. CONCLUSIONS: This is the first study, to our knowledge, to find a possible association between completed suicide and medications for allergic rhinitis and also the first report of an association of intranasal corticosteroid use with a lower suicide rate. This association should be considered preliminary and deserving of further investigation. PMID- 22075103 TI - Stepping back to step forward: lessons from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). PMID- 22075104 TI - Performance improvement CME: managing schizophrenia. AB - Schizophrenia is a highly disabling disorder characterized by positive and negative symptoms and poor functioning in almost every area of life. Multiple antipsychotics have demonstrated varying levels of efficacy in reducing symptoms in schizophrenia, but adverse effects are common, adherence to medication is low, and relapse rates are high. Psychosocial interventions used in conjunction with antipsychotic pharmacotherapy may help improve treatment outcomes. This Performance Improvement CME activity focuses on individualizing treatment for schizophrenia, assessing treatment adherence, minimizing medication-induced adverse events, and preventing relapse, for children, adolescents, and adults with schizophrenia. PMID- 22075105 TI - Moderators of antidepressant response in major depression. AB - Moderators are baseline variables that predict response to a treatment. Prognostic moderators predict response to all treatments, whereas prescriptive moderators predict differential response to particular treatments. In patients with major depressive disorder, prognostic variables include having anxious or chronic depression, living alone, and having psychiatric comorbidities. Prescriptive variables include gender, menopausal status, age and age at onset, depressive subtype, severity, and chronicity. Recognizing these variables can help clinicians better predict patients' response to treatment, select effective treatments for individual patients, and move patients to the next treatment step when response is inadequate. PMID- 22075106 TI - Recognizing and diagnosing ADHD in college students. AB - College students have greater independence, autonomy, and academic expectations than children and adolescents. Combined with the minimal structure and supervision provided on campus, the temptations and challenges of this transitional phase can exacerbate symptoms of undiagnosed attention deficit/hyperactivity disorder (ADHD) and lead to poor academic performance, social difficulties and interpersonal conflicts, financial problems, and substance use. Recognition by college personnel and proper evaluation and consistent follow-up by clinicians can help college students with ADHD get the treatment that they need in order to thrive in an academic setting. PMID- 22075107 TI - Coeliac disease and gluten avoidance in New Zealand children. AB - OBJECTIVES: Although gluten avoidance is thought to be common among New Zealanders, the prevalence of gluten avoidance and of actual coeliac disease (CD) in children is uncertain. Our aims were: (1) to determine the prevalence of doctor-diagnosed CD and of gluten avoidance in New Zealand children; and (2) among children without CD, to identify independent predictors of gluten avoidance. DESIGN: The New Zealand Asthma and Allergy Cohort Study has detailed information on participants' demographic, pregnancy-related and neonatal factors. The authors surveyed parents regarding their child's history of lactose intolerance and gluten-related issues (eg, gluten avoidance, history of wheat or gluten allergy in first degree relatives, testing and doctor diagnosis of CD). After excluding children with doctor-diagnosed CD, the authors identified independent predictors of gluten avoidance. RESULTS: Among 916 children, most (78%) were of European ethnicity. The authors identified nine (1.0%, 95% CI 0.5% to 1.9%) who had doctor-diagnosed CD, while 48 (5.2%, 95% CI 4.0% to 6.9%) avoided gluten. Among children without diagnosed CD, significant independent predictors for gluten avoidance were Christchurch site (OR 2.2, 95% CI 1.02 to 4.7), prior testing for CD (OR 9.0, 95% CI 4.1 to 19.5) and doctor-diagnosed lactose intolerance (OR 5.2, 95% CI 2.0 to 13.9). CONCLUSIONS: CD affected 1% of these New Zealand children, but 5% reported gluten avoidance. The predictors of gluten avoidance in children without doctor-diagnosed CD suggest important regional differences in community belief or medical practice regarding implementation of gluten avoidance and the contributory role of non-specific subjective abdominal complaints. PMID- 22075108 TI - Transverse colon volvulus presenting as 'inverted' coffee-bean sign. PMID- 22075109 TI - Effect of program type on the training experiences of 248 university, community, and US military-based general surgery residencies. AB - BACKGROUND: There is a paucity of research comparing resident training experiences of university, community, and military-affiliated surgical programs. STUDY DESIGN: We reviewed a cross-sectional national survey (NEARS) involving all US categorical general surgery residents (248 programs). Demographics and level of agreement regarding training experiences were collected. Statistical analysis included chi-square, ANOVA, and hierarchical logistic regression modeling (HLRM). RESULTS: There were 4,282 residents included (82.4% response rate). The majority (69%) trained in university programs. Types of programs differed by sex mix (p < 0.001), racial makeup (p = 0.005), marital status profile (p = 0.002), and parental status profile (p < 0.001). Community residents were most satisfied with their operative experience (community 84.5%, university 73.4%, military 62.4%; p < 0.001), most likely to feel their opinions are important (76.0% vs 69.4% vs 67.9%, respectively; p < 0.001), and least likely to believe attendings will think worse of them if residents asked for help with patient management (12.6% vs 15.9% vs 14.7%, respectively; p = 0.025). Military residents were least likely to report that surgical training is too long (military 7.4%, community 14.0%, university 23.8%; p < 0.001). On HLRM, community programs were independently associated with residents feeling their opinions are important (odds ratio [OR] 1.91; p < 0.001), and reporting satisfactory operative experience (OR 4.73; p < 0.001). Residents training at military programs (OR 0.23; p = 0.002) or community programs (OR 0.31; p < 0.001) were less likely to feel that surgical training is too long, or that attendings will think worse of them if asked for help with patient care (community OR 0.19; p < 0.001; military OR 0.27; p = 0.004). CONCLUSIONS: Residents at university, community, and military programs report distinct training experiences. These findings may inform programs of potential targeted strategies for enhanced support. PMID- 22075110 TI - Total parenteral nutrition therapy and liver injury: a histopathologic study with clinical correlation. AB - Total parenteral nutrition (TPN) therapy is a well-recognized cause of liver injury. The histologic changes attributed to TPN in the literature vary widely. In this study, we describe the histopathologic changes associated with TPN therapy and relate these changes to various clinical parameters. We conducted a retrospective study of 89 patients who underwent biopsy or liver transplantation while on TPN. We report that (1) ductopenia, a previously unreported finding, is seen in a significant number of patients on TPN. It is more frequently seen in patients with low stage of fibrosis and may have an inverse relationship with the length of therapy; (2) Perivenular fibrosis is a feature frequently seen in patients with high-stage portal fibrosis. In fact, we find the combination of portal and perivenular fibrosis to be a characteristic of TPN injury; (3) Infants are more susceptible to TPN-related hepatocellular injury, are more likely to develop fibrosis, and progress to high-stage fibrosis more rapidly than older children and adults; (4) Cholestasis, although more common in infants, is the most common pathologic finding in all age groups; (5) Steatosis is more commonly seen in older children and adults than in infants; (6) Progression to fibrosis in infants may be dependent on the length of therapy and the underlying disease for which TPN is administered; and (7) Clinical markers of liver injury (eg, elevated liver enzymes) do not predict the degree of hepatocellular injury or fibrosis, and therefore, serial biopsies may be indicated for patients on TPN therapy. PMID- 22075111 TI - Administrative database research has unique characteristics that can risk biased results. AB - OBJECTIVE: The provision of health care frequently creates digitized data--such as physician service claims, medication prescription records, and hospitalization abstracts--that can be used to conduct studies termed "administrative database research." While most guidelines for assessing the validity of observational studies apply to administrative database research, the unique data source and analytical opportunities for these studies create risks that can make them uninterpretable or bias their results. STUDY DESIGN: Nonsystematic review. RESULTS: The risks of uninterpretable or biased results can be minimized by; providing a robust description of the data tables used, focusing on both why and how they were created; measuring and reporting the accuracy of diagnostic and procedural codes used; distinguishing between clinical significance and statistical significance; properly accounting for any time-dependent nature of variables; and analyzing clustered data properly to explore its influence on study outcomes. CONCLUSION: This article reviewed these five issues as they pertain to administrative database research to help maximize the utility of these studies for both readers and writers. PMID- 22075112 TI - "Might" or "suggest"? No wording approach was clearly superior in conveying the strength of recommendation. AB - OBJECTIVE: To compare different wording approaches for conveying the strength of health care recommendations. STUDY DESIGN AND SETTING: Participants were medical residents in Canada and the United States. We randomized them to one of three wording approaches, each expressing two strengths of recommendation, strong and weak: (1) "we recommend," "we suggest;" (2) "clinicians should," "clinicians might;" (3) "we recommend," "we conditionally recommend." Each participant received one strong and one weak recommendation. For each recommendation, they chose a hypothetical course of action; we judged whether their choice was appropriate for the strength of the recommendation. RESULTS: The response rate was 77% (341/441). Most participants, in response to strong recommendations, chose hypothetical courses of action appropriate for weak recommendations. None of the wording approaches was clearly superior in conveying the strength of a recommendation. However, different approaches appeared superior depending on the strength and direction (for or against an intervention) of the recommendation. CONCLUSION: No wording approach was clearly superior in conveying the strength of recommendation. Guideline developers need to make the connection between the wording and their intended strength explicit. PMID- 22075113 TI - Evolutionary origins of transcription factor binding site clusters. AB - Empirical studies have revealed that regulatory DNA sequences such as enhancers or promoters often harbor multiple binding sites for the same transcription factor. Such "homotypic site clustering" has been hypothesized as arising out of functional requirements of the sequences. Here, we propose an alternative explanation of this phenomenon that multisite enhancers are common because they are favored by evolutionary sampling of the genotype-phenotype landscape. To test this hypothesis, we developed a new computational framework specialized for population genetic simulations of enhancer evolution. It uses a thermodynamics based model of enhancer function, integrating information from strong as well as weak binding sites, to determine the strength of selection. Using this framework, we found that even when simpler genotypes exist for a desired strength of regulation, relatively complex genotypes (enhancers with more sites) are more readily reached by the simulated evolutionary process. We show that there are more ways to "build" a fit genotype with many weak sites than with a few strong sites, and this is why evolution finds complex genotypes more often. Our claims are consistent with an empirical analysis of binding site content in enhancers characterized in Drosophila melanogaster and their orthologs in other Drosophila species. We also characterized a subtle but significant difference between genotypes likely to be sampled by evolution and equally fit genotypes one would obtain by uniform sampling of the fitness landscape, that is, an "evolutionary signature" in enhancer sequences. Finally, we investigated potential effects of other factors, such as rugged fitness landscapes, short local duplications, and noise characteristics of enhancers, on the emergence of homotypic site clustering. Homotypic site clustering is an important contributor to the complexity and function of cis-regulatory sequences. This work provides a simple null hypothesis for its origin, against which alternative adaptationist explanations may be evaluated, and cautions against "evolutionary mirages" present in common features of genomic sequence. The quantitative framework we develop here can be used more generally to understand how mechanisms of enhancer action influence their composition and evolution. PMID- 22075114 TI - Evidence for horizontal gene transfer from bacteroidetes bacteria to dinoflagellate minicircles. AB - Dinoflagellate protists harbor a characteristic peridinin-containing plastid that evolved from a red or haptophyte alga. In contrast to typical plastids that have ~100-200 kb circular genomes, the dinoflagellate plastid genome is composed of minicircles that each encode 0-5 genes. It is commonly assumed that dinoflagellate minicircles are derived from a standard plastid genome through drastic reduction and fragmentation. However, we demonstrate that the ycf16 and ycf24 genes (encoded on the Ceratium AF490364 minicircle), as well as rpl28 and rpl33 (encoded on the Pyrocystis AF490367 minicircle), are related to sequences from Algoriphagus and/or Cytophaga bacteria belonging to the Bacteroidetes clade. Moreover, we identified a new open reading frame on the Pyrocystis minicircle encoding a SRP54 N domain, which is typical of FtsY proteins. Because neither of these minicircles share sequence similarity with any other dinoflagellate minicircles, and their genes resemble bacterial operons, we propose that these Ceratium and Pyrocystis minicircles resulted from a horizontal gene transfer (HGT) from a Bacteroidetes donor. Our findings are the first indication of HGT to dinoflagellate minicircles, highlighting yet another peculiar aspect of this plastid genome. PMID- 22075115 TI - Evolution and function of the globin intergenic regulatory regions of the antarctic dragonfishes (Notothenioidei: Bathydraconidae). AB - As the Southern Ocean cooled to -1.8 degrees C over the past 40 My, the teleostean clade Notothenioidei diversified and, under reduced selection pressure for an oxygen-transporting apparatus, became less reliant on hemoglobin and red blood cells. At the extreme of this trend, the crown group of Antarctic icefishes (Channichthyidae) lost both components of oxygen transport. Under the decreased selection scenario, we hypothesized that the Antarctic dragonfishes (Bathydraconidae, the red-blooded sister clade to the icefishes) evolved lower blood hemoglobin concentrations because their globin gene complexes (alpha- and beta-globin gene pairs linked by a regulatory intergene) transcribe globin mRNAs less effectively than those of basal notothenioids (e.g., the Nototheniidae [notothens]). To test our hypothesis, we 1) sequenced the alpha/beta-intergenes of the adult globin complexes of three notothen and eight dragonfish species and 2) measured globin transcript levels in representative species from each group. The typical nototheniid intergene was ~3-4 kb in length. The bathydraconid intergenes resolved into three subclasses (long [3.8 kb], intermediate [3.0 kb], and short [1.5-2.3 kb]) that corresponded to the three subclades proposed for the taxon. Although they varied in length due to indels, the three notothen and eight dragonfish intergenes contained a conserved ~90-nt element that we have previously shown to be required for globin gene transcription. Using the quantitative polymerase chain reaction, we found that globin mRNA levels in red cells from one notothen species and from one species of each dragonfish subclade were equivalent statistically. Thus, our results indicate that the bathydraconids have evolved adult globin loci whose regulatory intergenes tend to be shorter than those of the more basal nototheniids yet are equivalent in transcriptional efficacy. Their low blood hemoglobin concentrations are most likely due to reduction in hematocrit. PMID- 22075116 TI - The role of GC-biased gene conversion in shaping the fastest evolving regions of the human genome. AB - GC-biased gene conversion (gBGC) is a recombination-associated evolutionary process that accelerates the fixation of guanine or cytosine alleles, regardless of their effects on fitness. gBGC can increase the overall rate of substitutions, a hallmark of positive selection. Many fast-evolving genes and noncoding sequences in the human genome have GC-biased substitution patterns, suggesting that gBGC-in contrast to adaptive processes-may have driven the human changes in these sequences. To investigate this hypothesis, we developed a substitution model for DNA sequence evolution that quantifies the nonlinear interacting effects of selection and gBGC on substitution rates and patterns. Based on this model, we used a series of lineage-specific likelihood ratio tests to evaluate sequence alignments for evidence of changes in mode of selection, action of gBGC, or both. With a false positive rate of less than 5% for individual tests, we found that the majority (76%) of previously identified human accelerated regions are best explained without gBGC, whereas a substantial minority (19%) are best explained by the action of gBGC alone. Further, more than half (55%) have substitution rates that significantly exceed local estimates of the neutral rate, suggesting that these regions may have been shaped by positive selection rather than by relaxation of constraint. By distinguishing the effects of gBGC, relaxation of constraint, and positive selection we provide an integrated analysis of the evolutionary forces that shaped the fastest evolving regions of the human genome, which facilitates the design of targeted functional studies of adaptation in humans. PMID- 22075117 TI - Secondary abdominal compartment syndrome in patients with toxic epidermal necrolysis. AB - INTRODUCTION: Secondary abdominal compartment syndrome (ACS) is a severe complication in patients admitted to burn intensive care units (BICUs). Unlike patients with thermal burns, patients with toxic epidermal necrolysis (TEN) present with a different pathophysiology and usually require less fluid. PATIENTS AND METHODS: We reviewed our registry of adult patients presenting with TEN in our 8-bed BICU over the course of 11 years and identified and analyzed patients treated for ACS and decompressive laparotomy (DL). RESULTS: From a total of 29 patients with bioptic confirmed TEN, 5 underwent DL due to ACS with a mean age of 57 years, mean percentage of total body surface area (TBSA) affected of 54+/-25%, complete epidermolysis of 28+/-24% TBSA, a mean severity of illness score (SCORTEN) of 3.8+/-0.8, and a mean intra-abdominal pressure before DL of 33+/-7 mmHg. Mortality was 100% in patients with ACS versus 33% without ACS. CONCLUSION: An ACS that requires DL worsens the already critical condition of a TEN patient considerably. TEN-related impaired intestinal functionality and increasing intestinal edema due to systemic capillary leakage warrant early initiation of intra-abdominal pressure monitoring to identify patients at high risk of ACS. PMID- 22075118 TI - Family function and social support in Iranian self-immolated women. AB - AIM: The significance of family function and social support in Iranian self immolated women was investigated in this study. METHODS: In a prospective design, we selected 53 cases (31 self-immolated women and 22 women with unintentional burn) from Tehran and Shiraz burn centre (Motahari and Ghotbeddin Shirazi, respectively). The average age of the experimental group was 26.19 (S=7.11) with a burn percentage of 46.11 (S=25.52), and the average age of the control group was 29.15 (S=5.12) and their burn percentage was 43 (S=25.98). Along with Demographic Information Questionnaire, participants were administered Family Assessment Device (FAD) and Social Support Scale (SSS). To analyse data, we used chi-square test (chi(2)), t-test, multivariate analysis of variance (MANOVA) and also logistic regression analysis. RESULTS: Data showed that the difference of Family Function sub-scales between the experimental and control groups was not significant (Wilk's lambda=0.75, F=1.67, df=(8, 51), P<0.05). On the other hand, two independent sample t-tests showed a significant difference of Social Support between the two groups (t=-3.31, df=51, P<0.002). CONCLUSIONS: Consistent with previous studies, this research showed that the less Social Support one perceives the more one at risk for self-immolation. Although the mean scores of FAD sub scales in control group were more than experimental group, there was no significant difference between the two groups. PMID- 22075119 TI - Engaging medical students in the feedback process. AB - BACKGROUND: There are potential advantages to engaging medical students in the feedback process, but efforts to do so have yielded mixed results. The purpose of this study was to evaluate a student-focused feedback instructional session in an experimental setting. METHODS: Medical students were assigned randomly to either the intervention or control groups and then assigned randomly to receive either feedback or compliments. Tests of knowledge, skills, and attitudes were given before and after the intervention. RESULTS: There was a significant gain of knowledge and skill in the group that received instruction. Satisfaction was higher after compliments in the control group but higher after feedback in the instructional group. There was no change in the subject's willingness to seek feedback. CONCLUSIONS: A student-focused component should be carefully included as part of an overall effort to improve feedback in surgical education. The role of medical student attitudes about feedback requires further investigation. PMID- 22075120 TI - A novel multimodal platform for assessing surgical technical skills. AB - BACKGROUND: Established methods for assessing surgical performance face limitations. Global rating scales and procedure-specific checklists are resource intensive and rely on expert opinions. Alternatives that use technology to track hand movements, such as magnetic and optical tracking systems, are generally expensive and ill suited to the surgical environment. METHODS: The authors present a new platform that integrates a novel, low-cost optical tracking system, magnetic tracking technology and a videographic recording system to quantify surgical performance synchronously across all modalities. The validity of this platform was tested by examining its ability to differentiate between the performance of expert and novice participants on a basic surgical task. RESULTS: Each modality was able to differentiate between expert and novice participants, and metrics were well correlated across modalities. CONCLUSIONS: The authors have developed a platform for assessing surgical performance. It can operate in the absence of expert raters and has the potential to provide immediate feedback to trainees. PMID- 22075121 TI - Magnesium alloys as body implants: fracture mechanism under dynamic and static loadings in a physiological environment. AB - It is essential that a metallic implant material possesses adequate resistance to cracking/fracture under the synergistic action of a corrosive physiological environment and mechanical loading (i.e. stress corrosion cracking (SCC)), before the implant can be put to actual use. This paper presents a critique of the fundamental issues with an assessment of SCC of a rapidly corroding material such as magnesium alloys, and describes an investigation into the mechanism of SCC of a magnesium alloy in a physiological environment. The SCC susceptibility of the alloy in a simulated human body fluid was established by slow strain rate tensile (SSRT) testing using smooth specimens under different electrochemical conditions for understanding the mechanism of SCC. However, to assess the life of the implant devices that often possess fine micro-cracks, SCC susceptibility of notched specimens was investigated by circumferential notch tensile (CNT) testing. CNT tests also produced important design data, i.e. threshold stress intensity for SCC (KISCC) and SCC crack growth rate. Fractographic features of SCC were examined using scanning electron microscopy. The SSRT and CNT results, together with fractographic evidence, confirmed the SCC susceptibility of both smooth and notched specimens of a magnesium alloy in the physiological environment. PMID- 22075123 TI - Evaluation of the ultrasonication process for injectability of hydraulic calcium phosphate pastes. AB - This study examined the use of ultrasonication to improve the injectability of an aqueous calcium phosphate paste. Ultrasonication was applied to the paste through the plunger of the delivery syringe. A factorial design of experiments with three investigated factors, liquid to powder ratio (LPR) (38%, 39% and 40%), the size of the delivery syringe (5 and 10 ml) and the amplitude of the 20 kHz power ultrasonication (0-30 MUm), was used in this study. The volume fraction of the extruded paste was used to quantify injectability. Small injectability improvements were observed with an increase in LPR and decrease in syringe size, which is consistent with previously published results. The improvements due to ultrasonication were significant and remarkable. For example, when using the 5 ml syringe the injected volume fraction of the 38% LPR paste improved from 63.4 +/- 2.3% without ultrasonication to 97.3 +/- 2.4% with 30%. This result shows that ultrasonication is an effective solution to improve injectability. PMID- 22075122 TI - Effects of structural properties of electrospun TiO2 nanofiber meshes on their osteogenic potential. AB - Ideal outcomes in the field of tissue engineering and regenerative medicine involve biomaterials that can enhance cell differentiation and production of local factors for natural tissue regeneration without the use of systemic drugs. Biomaterials typically used in tissue engineering applications include polymeric scaffolds that mimic the three-dimensional structural environment of the native tissue, but these are often functionalized with proteins or small peptides to improve their biological performance. For bone applications, titanium implants, or more appropriately the TiO2 passive oxide layer formed on their surface, have been shown to enhance osteoblast differentiation in vitro and to promote osseointegration in vivo. In this study we evaluated the effect on osteoblast differentiation of pure TiO2 nanofiber meshes with different surface microroughness and nanofiber diameters, prepared by the electrospinning method. MG63 cells were seeded on TiO2 meshes, and cell number, differentiation markers and local factor production were analyzed. The results showed that cells grew throughout the entire surfaces and with similar morphology in all groups. Cell number was sensitive to surface microroughness, whereas cell differentiation and local factor production was regulated by both surface roughness and nanofiber diameter. These results indicate that scaffold structural cues alone can be used to drive cell differentiation and create an osteogenic environment without the use of exogenous factors. PMID- 22075124 TI - The Pentax-AWS video laryngoscope for emergency airway management. PMID- 22075125 TI - Confidence intervals and adjusted odds ratios: a commend on interpreting the results of Killip classification and glucose levels. PMID- 22075126 TI - Anaphylaxis-induced hyperfibrinogenolysis and the risk of Kounis syndrome: the dual action of tryptase. PMID- 22075127 TI - Complex asymmetric male genitalia of Anevrina Lioy (Diptera: Phoridae). AB - Detailed structure of the male genitalia of Anevrina is described. Hitherto unknown morphological characters of the internal sclerites relating to the epandrium and hypandrium are illustrated and elucidated. The subepandrial sclerite + bacilliform sclerites are distinctly modified, and the typical subepandrial sclerite is not recognizable. The right base of the medially shifted right surstylus is not connected to the posterior margin of the epandrium, and is directly supported by a robust bacilliform sclerite. The robust bacilliform sclerites are greatly developed inside the epandrium, and extended to three clasping components, the left surstylus, the medially shifted right surstylus and a pair of clasping lobes on the posteroventral margin of the right side of the epandrium. The upper lobe of a pair of clasping lobes on the right side of the epandrium is considered to originally have been situated on the left side and subsequently shifted to the right side. The plesiomorphic state of the clasping components relative to Anevrina is thought to be symmetrically four, comprising both the left and right surstyli and the posterior edge of both sides of the epandrium, indicating that the amazing phenomenon of cross-shifting of the clasping components has occurred in Anevrina. A cladogram generated based on the genitalic characters observed in this study shows sister groups within Anevrina, namely an Anevrina urbana-group comprised of A. urbana, A. setigera, A. olympiae, A. variabilis, A. thoracica, and an Anevrina unispinosa-group comprised of A. unispinosa, A. curvinervis, A. luggeri and A. macateei. PMID- 22075128 TI - Cephalic morphology of Hymenopus coronatus (Insecta: Mantodea) and its phylogenetic implications. AB - External and internal head structures of the mantodean Hymenopus coronatus are examined and described in detail. The results are elaborately compared with the literature. Strong crests on the anterior tentorial arms that articulate with the subantennal suture, a parietal suture and glossae and paraglossae with anteriorly bent tips are proposed as new potential apomorphies for Mantodea while a head capsule being wider than long, enlarged compound eyes, the presence of a frontal shield or scutellum, lateral lobes in the anterior tentorial arms, the presence of a transverse and an interantennal suture and the reduction of the mentum are confirmed as apomorphies, As potential apomorphies for Dictyoptera the reduction of Musculus tentoriobuccalis lateralis (M. 49) is newly presented and a "perforate" tentorium, lacinial incisivi that are located in a galeal pouch and the presence of a postmola are confirmed. The present study shows the value of cephalic morphology for phylogenetic analysis but also points out that further studies including evolutionary key taxa are essential for resolving the evolutionary adaptations among dictyopterans. PMID- 22075129 TI - Microscopic anatomy of male tegumental glands and associated cuticular structures in Titanethes albus (Crustacea: Isopoda). AB - Male glandular organs characterized by porous surfaces with hair-like cuticular elaborations are known from several trichoniscid isopods. In the subterranean species Titanethes albus, males possess paired tubercles with numerous hairs and pores dorsally on the pleon. We analyzed the microscopic anatomy of these structures with scanning and transmission electron microscopy. Diverse epicuticular formations and numerous sensilla, which are probably chemoreceptive, are present on the tubercles. We found several secretory surfaces on the pleon in addition to the dorsal tubercles. We also examined the distribution, architecture and ultrastructure of male-specific glands in T. albus with light and transmission electron microscopy. Three distinct types of male-specific rosette glands are present in different parts of the pleon and in the uropods. Glands secreting on the dorsal tubercles contain stellar central cells. The ultrastructure and histochemical staining properties of male-specific glands in T. albus suggest that they produce peptides which might function as contact pheromones. PMID- 22075130 TI - [Assessment of a residency training program in endocrinology and nutrition: results of a resident survey]. AB - INTRODUCTION: In 2006, a new training program was approved for resident physicians in endocrinology and nutrition (EN). A survey was conducted to EN residents to assess their training, their depth of knowledge, and compliance with the new program, as well as potential changes in training, and the results obtained were compared to those from previous surveys. MATERIAL AND METHODS: A survey previously conducted in 2000 and 2005 was used for this study. The survey included demographic factors, questions about the different rotations, scientific and practical training, assessment of their training departments and other aspects. Results of the current survey were compared to those of the 2005 survey. RESULTS: The survey was completed by 40 residents. Mandatory rotations are mainly fulfilled, except for neurology. Some rotations removed from the program, such as radiology and nuclear medicine, still are frequently performed and popular among residents, who would include them back into the program. There was a low compliance with practical training in the endocrinology area. Forty percent of residents were not aware of the new program, but 60% thought that it was fulfilled. A total of 82.5% of residents thought that their departments fulfilled the training objectives. CONCLUSIONS: Few differences were found in rotations as compared to the data collected in 2005 despite changes in the training program, and there was still a lack of practical training. By contrast, rating of training received from departments and senior physicians was improved as compared to prior surveys. PMID- 22075131 TI - Crystal structure of Apis mellifera OBP14, a C-minus odorant-binding protein, and its complexes with odorant molecules. AB - Apis mellifera (Amel) relies on its olfactory system to detect and identify new sources of floral food. The Odorant-Binding Proteins (OBPs) are the first proteins involved in odorant recognition and interaction, before activation of the olfactory receptors. The Amel genome possess a set of 21 OBPs, much fewer compared to the 60-70 OBPs found in Diptera genomes. We have undertaken a structural proteomics study of Amel OBPs, alone or in complex with odorant or model compounds. We report here the first 3D structure of a member of the C-minus class OBPs, AmelOBP14, characterized by only two disulfide bridges of the three typical of classical OBPs. We show that AmelOBP14 possesses a core of 6 alpha helices comparable to that of classical OBPs, and an extra exposed C-terminal helix. Its binding site is located within this core and is completely closed. Fluorescent experiments using 1-NPN displacement demonstrate that AmelOBP14 is able to bind several compounds with sub micromolar dissociation constants, among which citralva and eugenol exhibit the highest affinities. We have determined the structures of AmelOBP14 in complex with 1-NPN, eugenol and citralva, explaining their strong binding. Finally, by introducing a double cysteine mutant at positions 44 and 97, we show that a third disulfide bridge was formed in the same position as in classical OBPs without disturbing the fold of AmelOBP14. PMID- 22075132 TI - Surgical management with or without a nasogastric tube in esophageal repairs. AB - OBJECTIVE: The aim of the study was to compare surgical management with or without a nasogastric tube (NGT) to prevent anastomotic stricture that occurred following esophageal repairs (ERs). METHODS: Twelve New Zealand rabbits were divided equally into 2m: with a NGT (experimental group) and without a NGT (control group). A 1-cm-length of the cervical esophagus was resected through a cervical incision and then anastomosis was performed using the NGT and keeping it in place for 6 days in the experimental group. The same procedures were performed in the control group. Both groups were fed parenterally for 6 days and orally after esophagography on postoperative day 7 as long as there was no esophageal leakage. The rabbits were sacrificed to evaluate diameter of the esophageal lumen (DOTEL), bursting pressure (BP), tissue hydroxyproline (HP) and wound healing scores (WHSs) in the anastomosis lines 8 weeks later. RESULTS: In the experimental group, DOTEL, BP, and HP were significantly lower than they were in the control group. WHSs in the experimental group were not higher than they were in the control group. CONCLUSIONS: Surgical management without a NGT is more effective than management with a NGT in ERs as shown by increased DOTEL, BP, and HP levels. PMID- 22075133 TI - Comparison of bilateral and unilateral cochlear implants in children with sequential surgery. AB - OBJECTIVE: The objective of this study was to evaluate the effect of bilateral versus unilateral cochlear implants and the importance of the inter-implant interval. METHODS: Seventy-three prelingually deaf children received sequential bilateral cochlear implants. Speech recognition in quiet with the first, second and with both implants simultaneously was evaluated at the time of the second implantation and after 12 and 24 months. RESULTS: Mean bilateral speech recognition 12 and 24 months after the second implantation was significantly higher than that obtained with either the first or the second implant. The addition of a second implant was demonstrated to have a beneficial effect after both 12 and 24 months. Speech recognition with the second implant increased significantly during the first year. A small, non-significant improvement was observed during the second year. The inter-implant interval significantly influenced speech recognition with the second cochlear implant both at 12 and 24 months, and bilateral speech recognition at 12 months, but not at 24 months. CONCLUSIONS: A small, but statistically significant improvement in speech recognition was found with bilateral cochlear implants compared with a unilateral implant. A major increase in speech recognition occurred with the second cochlear implant during the first year. A shorter time interval between the two implantations resulted in better speech recognition with the second implant. However, no definitive time-point was found for when the second implant could no longer add a positive effect. PMID- 22075134 TI - Microscopic comparison of topical use of Mitomycin C and Fluorouracil on cold knife myringotomy. AB - Objective/hypothesis A comparison of the histopathological effect of topical use of Mitomycin C and 5-Fluorouracil in preventing myringotomy closure in rats. STUDY DESIGN: clinical trial. Methods and materials The study was performed on 43 rats that were divided into three groups. Study groups (A and B) and control group (C) after bilateral cold-knife myringotomy, we applied Mitomycin C (MMC) 4mg/ml to group A, 5-Fluouracil (5FU) 50mg/ml to group B, and normal saline to group C. An examination of all ears of rats was carried out by otoscope on days 0, 1, 3, 5, 7, and then every five days up to 70 days. Each day's closed myringotomies of all groups were examined. Results The mean of post myringotomy opening time was 37, 16, and 12 days respectively in MMC, 5FU, and saline. Patency duration of MMC group was significantly long (p<0.0001), but in histopatholgical examinations, sclerosis of tympanic membrane in MMC group showed the highest patency duration (p<0.0001). Conclusion Mitomycin C significantly prolonged the duration of myringotomy patency time - longer than 5-Fluouracil and saline but with the adverse effects of tympanic membrane fibrosis. PMID- 22075135 TI - Mid-esophagus unresectable cancer treated with a low cost stent. First experience. AB - BACKGROUND: In the cancer of the esophagus, with recent technologic advances, self-expanding metal stents (SEMS) are at the forefront of the armamentarium for re-establishing luminal patency. Weighed against the numerous advantages of stents are the import conditions and the cost. In light of this, we tested new low cost prostheses having the basic needs and characteristics to aim a significant benefit to poor people having advanced esophageal cancer, in a Brazilian regional public hospital. METHODS: This initial experience included fifteen patients (eleven men and four women, 55 +/- 6.17 years old), presenting esophageal cancer, located at the medium third of the thoracic esophagus, extending for 5.5-8 cm long, not suitable for surgical procedure because they had been staged on fourth grade of the disease, two of them having fistula communicating esophagus to respiratory tree. The stents were placed under endoscopic and fluoroscopic guidance, after attempting an esophageal dilatation. An appropriate covered stent was then deployed, twelve of 10 cm and three of 13 cm in length. A chest X-ray was done 2 h after the procedure and a barium swallow was performed within 12 hours. Seven days and monthly until complete a six month follow-up after the procedure the patients were questioned about presence of pain, regurgitation, heartburn, cough, and their alimentary behavior. RESULTS: There were no severe complications and transient mild chest pain resolved until the seventh day after the stent deployment. Chest X-ray demonstrated expansion of the stent in all patients. In 2 cases of fistula, a barium swallow showed its complete sealing. The completion of the proposed follow-up was not achieved in three cases, limited by the patient's death until the third month, due to cancer progression. Recurrent dysphagia to paste food accounted for by tumor overgrowth proximal or distal to the stent and stent migration were not observed in the series. CONCLUSIONS: The new low cost endoprostheses is effective and forthcoming increased experience and prospective trials including questionnaires to analyze quality of life will allow for more informed decisions tailoring to a particular patient situation or to unexpected complications. PMID- 22075136 TI - Tea consumption, incidence and long-term prognosis of a first acute myocardial infarction--the SHEEP study. AB - BACKGROUND & AIMS: Results of previous studies on tea consumption and incidence or prognosis of acute myocardial infarction (AMI) are conflicting. The aim of the present study was to examine the potential role of tea consumption in the previous 12 months in primary and secondary prevention of AMI. METHODS: We studied a total of 1340 individuals with a first non-fatal AMI and 2303 frequency matched control participants on age, gender and hospital catchment area including querying their tea consumption over the previous 12 months. The cohort of AMI cases was then followed for total and cardiac mortality and for non-fatal cardiovascular events with national registers over 8 years. Estimates of relative risks for a first AMI were based on odds ratios from unconditional logistic regression and Cox proportional hazards models were used to examine the prognostic importance of tea consumption in the cohort of cases. RESULTS: The prevalence of daily tea consumption was 20.5% among cases and 21.5% among controls. Tea consumption was associated with a lower risk for a first AMI with adjustment for matching criteria alone, with an odds ratio of 0.78 (95% confidence interval, 0.64-0.95) comparing those who consumed tea daily to those never consuming tea. However, in multivariable adjusted model there was no evidence for an association, the corresponding odds ratio was 1.08(0.86-1.36). There was also no association between tea consumption and cardiac mortality and non-fatal cardiovascular events, with a corresponding adjusted hazard ratio of 0.99(0.77-1.27). CONCLUSIONS: In this epidemiological study, greater tea consumption in the previous year was associated with a lower risk of AMI. However, a clear association between tea consumption and the incidence or prognosis of AMI was not demonstrated, probably because of tea drinkers having a healthier lifestyle. PMID- 22075137 TI - Borylation and silylation of C-H bonds: a platform for diverse C-H bond functionalizations. AB - Methods that functionalize C-H bonds can lead to new approaches for the synthesis of organic molecules, but to achieve this goal, researchers must develop site selective reactions that override the inherent reactivity of the substrates. Moreover, reactions are needed that occur with high turnover numbers and with high tolerance for functional groups if the C-H bond functionalization is to be applied to the synthesis of medicines or materials. This Account describes the discovery and development of the C-H bond functionalization of aliphatic and aromatic C-H bonds with borane and silane reagents. The fundamental principles that govern the reactivity of intermediates containing metal-boron bonds are emphasized and how an understanding of the effects of the ligands on this reactivity led us to broaden the scope of main group reagents that react under mild conditions to generate synthetically useful organosilanes is described. Complexes containing a covalent bond between a transition metal and a three coordinate boron atom (boryl complexes) are unusually reactive toward the cleavage of typically unreactive C-H bonds. Moreover, this C-H bond cleavage leads to the formation of free, functionalized product by rapid coupling of the hydrocarbyl and boryl ligands. The initial observation of the borylation of arenes and alkanes in stoichiometric processes led to catalytic systems for the borylation of arenes and alkanes with diboron compounds (diborane(4) reagents) and boranes. In particular, complexes based on the Cp*Rh (in which Cp is the cyclopentadienyl anion) fragment catalyze the borylation of alkanes, arenes, amines, ethers, ketals, and haloalkanes. Although less reactive toward alkyl C-H bonds than the Cp*Rh systems, catalysts generated from the combination of bipyridines and iridium(I)-olefin complexes have proven to be the most reactive catalysts for the borylation of arenes. The reactions catalyzed by these complexes form arylboronates from arenes with site-selectivity for C-H bond cleavage that depends on the steric accessibility of the C-H bonds. These complexes also catalyze the borylation of heteroarenes, and the selectivity for these substrates is more dependent on electronic effects than the borylation of arenes. The products from the borylation of arenes and heteroarenes are suitable for a wide range of subsequent conversions to phenols, arylamines, aryl ethers, aryl nitriles, aryl halides, arylboronic acids, and aryl trifluoroborates. Studies of the electronic properties of the ancillary ligand on the rate of the reaction show that the flat structure and the strong electron-donating property of the bipyridine ligands, along with the strong electron-donating property of the boryl group and the presence of a p-orbital on the metal-bound atom, lead to the increased reactivity of the iridium catalysts. Based on this hypothesis, we studied catalysts containing substituted phenanthroline ligands for a series of additional transformations, including the silylation of C-H bonds. A sequence involving the silylation of benzylic alcohols, followed by the dehydrogenative silylation of aromatic C-H bonds, leads to an overall directed silylation of the C-H bond ortho to hydroxyl functionality. PMID- 22075139 TI - Management of a pterygopalatine fossa hydatid cyst. AB - Hydatid cyst disease is a rare parasitic infestation caused by larvae of Echinococcus granulosus. Although larval stage of this parasite can thrive in any part of the body, especially lungs and liver; head and neck involvement is rare. Pterygopalatine fossa involvement is reported in two cases in the literature. In this report we represent a case with solitary, secondary pterygopalatine fossa hydatid cyst extending in to the maxillary sinus, orbita, sphenoid sinus and skull base. PMID- 22075138 TI - Two cases of peritonsillar abscess complicated by von Willebrand disease. AB - Von Willebrand disease (vWD) is a common hereditary bleeding disorder resulting from a quantitative and/or qualitative deficiency of von Willebrand factor (vWF). We report two cases of peritonsillar abscess complicated by vWD. A 46-year-old Japanese man was intravenously administered factor VIII clotting antigen (500U*3 days)and platelet transfusion (10U), when before puncture was performed. After puncture, his symptoms promptly improved with the administration of the antibiotic doripenem (DRPM, 1.5g/day). He left our facility one week later and had no recurrence of symptoms. A 24-year-old Japanese woman was intravenously administered factor VIII clotting antigen (4500U*3 days) and desmopressin (DDAVP) before undergoing a puncture. Her symptoms promptly improved with DRPM treatment (1.5g/day). The patient left our facility one week later. However, the peritonsillar abscess recurred in three weeks. Afterwards, tonsillectomy was enforced three months later. Intravenous factor VIII clotting antigen (4500U*2 days) and platelet transfusion (10U*1 day) had been used before tonsillectomy. We therefore suggest that a peritonsillar abscess in patients with vWD can be safely treated by factor VIII clotting antigen and DDAVP at the appropriate disease stage and by performing paracentesis for the acute phase or tonsillectomy for the chronic phase. PMID- 22075140 TI - Multifocal papillary thyroid carcinoma associated with primary amyloid goiter. AB - Amyloid goiter is a rare condition characterized by a diffuse enlargement of the thyroid gland due to amyloid deposition. Extremely uncommon is the development of differentiated carcinomas within this type of lesion. We describe to our knowledge the sixth case of a papillary thyroid carcinoma within an amyloid goiter, arising in a 45-year old woman with chronic renal failure due to primary amyloidosis. This is the first case of a multifocal papillary carcinoma within an amyloid goiter which produces compressive symptoms. The patient suffered a total thyroidectomy with the histological diagnosis of amyloid goiter with a multifocal papillary carcinoma of follicular variant. The Congo red stain confirmed the diagnosis of amyloid goiter. Two years and a half after the surgery the patient is free of recurrence. Amyloid goiter can hide a differentiated carcinoma. To diagnose and early treat this pathology, the knowledge of the possible association between an amyloid goiter and a differentiated carcinoma is needed. PMID- 22075141 TI - Meiotic pairing as a polo match. AB - In C. elegans, meiotic chromosome pairing is initiated by association of chromosomal sites known as pairing centers (PCs) with the nuclear periphery. The Dernburg and Zetka laboratories have shown that recruitment of Polo kinases to PCs at the nuclear envelope is essential to promote PC complex aggregation, pairing, and synapsis. PMID- 22075142 TI - Speed reading for genes: bookmarks set the pace. AB - During mitosis, most transcription ceases. Mitotic gene bookmarking marks genes for reactivation to ensure reestablishment of transcription states and cell-cycle progression. In a recent issue of Nature Cell Biology, Zhao et al. (2011) investigate how gene bookmarking leads to accelerated kinetics of transcriptional reactivation after mitosis. PMID- 22075143 TI - Autophagic factors cut to the bone. AB - Autophagy is an intracellular membrane-trafficking pathway for the delivery of proteins and organelles to lysosomes for degradation and recycling. DeSelm and coworkers (2011) now describe an essential role for autophagic proteins in the trafficking and fusion of lysosomes at the site of bone resorption: the osteoclast ruffled border. PMID- 22075144 TI - Phosphatidylinositol synthase and diacylglycerol platforms bust a move. AB - Kim et al. (2011) challenge the dogma that phosphatidylinositol synthesis is restricted to the endoplasmic reticulum (ER) by showing that a mobile membrane compartment transports phosphatidylinositol synthase from the ER to numerous cellular compartments, including the plasma membrane. These findings significantly impact our view of phosphoinositide signaling in the cell. PMID- 22075145 TI - A highly dynamic ER-derived phosphatidylinositol-synthesizing organelle supplies phosphoinositides to cellular membranes. AB - Polyphosphoinositides are lipid signaling molecules generated from phosphatidylinositol (PtdIns) with critical roles in vesicular trafficking and signaling. It is poorly understood where PtdIns is located within cells and how it moves around between membranes. Here we identify a hitherto-unrecognized highly mobile membrane compartment as the site of PtdIns synthesis and a likely source of PtdIns of all membranes. We show that the PtdIns-synthesizing enzyme PIS associates with a rapidly moving compartment of ER origin that makes ample contacts with other membranes. In contrast, CDP-diacylglycerol synthases that provide PIS with its substrate reside in the tubular ER. Expression of a PtdIns specific bacterial PLC generates diacylglycerol also in rapidly moving cytoplasmic objects. We propose a model in which PtdIns is synthesized in a highly mobile lipid distribution platform and is delivered to other membranes during multiple contacts by yet-to-be-defined lipid transfer mechanisms. PMID- 22075146 TI - Dual role of BKI1 and 14-3-3 s in brassinosteroid signaling to link receptor with transcription factors. AB - The plasma membrane-localized plant steroid hormone receptor, BRASSINOSTEROID INSENSITIVE 1 (BRI1), is quiescent in the absence of steroids, largely due to a negative regulator, BRI1 KINASE INHIBITOR 1 (BKI1). Here, we report that the steroid-induced, plasma membrane-dissociated and phosphorylated BKI1 also plays positive roles in BR signaling by interacting with a subset of 14-3-3 proteins. The cytosolic fraction of BKI1 carboxyl terminal region enhances BR signaling. Mutations of two serine residues in this region lead to reduced phosphorylation by the BRI1 kinase and constitutive plasma membrane localization. The 14-3-3 proteins can interact with the phosphorylated BKI1 through a motif that contains the two phosphorylation sites to release inhibition of BRI1 by BKI1. Meanwhile, the cytosolic BKI1 antagonizes the 14-3-3 s and enhances accumulation of BRI1 EMS SUPPRESSOR 1 (BES1)/BRASSINAZOLE RESISTANT 1 (BZR1) in the nucleus to regulate BR responses. PMID- 22075148 TI - The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. AB - The Salvador-Warts-Hippo (SWH) pathway is a complex signaling network that controls both developmental and regenerative tissue growth. Using a genetic screen in Drosophila melanogaster, we identified the sterile 20-like kinase, Tao 1, as an SWH pathway member. Tao-1 controls various biological phenomena, including microtubule dynamics, animal behavior, and brain development. Here we describe a role for Tao-1 as a regulator of epithelial tissue growth that modulates activity of the core SWH pathway kinase cassette. Tao-1 functions together with Hippo to activate Warts-mediated repression of Yorkie. Tao-1's ability to control SWH pathway activity is evolutionarily conserved because human TAO1 can suppress activity of the Yorkie ortholog, YAP. Human TAO1 controls SWH pathway activity by phosphorylating, and activating, the Hippo ortholog, MST2. Given that SWH pathway activity is subverted in many human cancers, our findings identify human TAO kinases as potential tumor suppressor genes. PMID- 22075147 TI - Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway. AB - Recent studies have shown that the Hippo-Salvador-Warts (HSW) pathway restrains tissue growth by phosphorylating and inactivating the oncoprotein Yorkie. How growth-suppressive signals are transduced upstream of Hippo remains unclear. We show that the Sterile 20 family kinase, Tao-1, directly phosphorylates T195 in the Hippo activation loop and that, like other HSW pathway genes, Tao-1 functions to restrict cell proliferation in developing imaginal epithelia. This relationship appears to be evolutionarily conserved, because mammalian Tao-1 similarly affects MST kinases. In S2 cells, Tao-1 mediates the effects of the upstream HSW components Merlin and Expanded, consistent with the idea that Tao-1 functions in tissues to regulate Hippo phosphorylation. These results demonstrate that one family of Ste20 kinases can activate another and identify Tao-1 as a component of the regulatory network controlling HSW pathway signaling, and therefore tissue growth, during development. PMID- 22075149 TI - Anterior visceral endoderm directs ventral morphogenesis and placement of head and heart via BMP2 expression. AB - In amniotes, ventral folding morphogenesis achieves gut internalization, linear heart tube formation, ventral body wall closure, and encasement of the fetus in extraembryonic membranes. Impairment of ventral morphogenesis results in human birth defects involving body wall, gut, and heart malformations and in mouse misplacement of head and heart. Absence of knowledge about genetic pathways and cell populations directing ventral folding in mammals has precluded systematic study of cellular mechanisms driving this vital morphogenetic process. We report tissue-specific mouse mutant analyses identifying the bone morphogenetic protein (BMP) pathway as a key regulator of ventral morphogenesis. BMP2 expressed in anterior visceral endoderm (AVE) signals to epiblast derivatives during gastrulation to orchestrate initial stages of ventral morphogenesis, including foregut development and positioning of head and heart. These findings identify unanticipated functions for the AVE in organizing the gastrulating embryo and indicate that visceral endoderm-expressed BMP2 coordinates morphogenetic cell behaviors in multiple epiblast lineages. PMID- 22075150 TI - Kinetochore-dependent microtubule rescue ensures their efficient and sustained interactions in early mitosis. AB - How kinetochores regulate microtubule dynamics to ensure proper kinetochore microtubule interactions is unknown. Here, we studied this during early mitosis in Saccharomyces cerevisiae. When a microtubule shrinks and its plus end reaches a kinetochore bound to its lateral surface, the microtubule end attempts to tether the kinetochore. This process often fails and, responding to this failure, microtubule rescue (conversion from shrinkage to growth) occurs, preventing kinetochore detachment from the microtubule end. This rescue is promoted by Stu2 transfer (ortholog of vertebrate XMAP215/ch-TOG) from the kinetochore to the microtubule end. Meanwhile, microtubule rescue distal to the kinetochore is also promoted by Stu2, which is transported by a kinesin-8 motor Kip3 along the microtubule from the kinetochore. Microtubule extension following rescue facilitates interaction with other widely scattered kinetochores, diminishing long delays in collecting the complete set of kinetochores by microtubules. Thus, kinetochore-dependent microtubule rescue ensures efficient and sustained kinetochore-microtubule interactions in early mitosis. PMID- 22075153 TI - Comments regarding 'Infrainguinal bypass for peripheral arterial occlusive disease: when arms save legs'. PMID- 22075154 TI - Circulating lipoprotein-associated phospholipase A2 in high-grade carotid stenosis: a new biomarker for predicting unstable plaque. AB - OBJECTIVE: To test plasma levels of lipoprotein-associated phospholipase A2 (Lp PLA2) in patients with high-grade carotid stenosis according to plaque histology. METHODS: This cross-sectional single-centre study included patients with >=70% North American Symptomatic Carotid Endarterectomy Trial (NASCET) carotid stenosis, who were treated surgically. Serum Lp-PLA2 and high-sensitivity C reactive protein (hs-CRP) were determined on the day of surgery. Histopathological analysis classified carotid plaque as stable or unstable, according to AHA classification. RESULTS: Of the 42 patients (mean age 70.4 +/- 10.5 years; 67% men), neurological symptoms were present in 16 (38%). Unstable plaques were found in 23 (55%). Median plasma level of Lp-PLA2 was significantly higher in patients with unstable plaque compared to those with stable plaque (222.4 (174.9-437.5) interquartile range (IQR) 63.5 vs. 211.1 (174.9-270.6) IQR 37.2 ng ml(-1); p = 0.02). Moreover, median Lp-PLA2 level were higher in asymptomatic patients with unstable plaque (226.8 ng ml(-1) (174.9-437.5) IQR 76.8) vs. stable plaque (206.9 ng ml(-1) (174.9-270.6) IQR 33.7; p = 0.16). Logistic regression showed that only the neurological symptoms (OR = 30.9 (3.7 244.6); p < 0.001) and the plasma Lp-PLA2 level (OR = 1.7 (1.1-12.3); p = 0.03) were independently associated with unstable carotid plaque as defined by histology. CONCLUSIONS: This study showed that circulating Lp-PLA2 was increased in patients with high-grade carotid stenosis and unstable plaque. Lp-PLA2 may be a relevant biomarker to guide for invasive therapy in asymptomatic patients with carotid artery disease. PMID- 22075155 TI - Anti-adhesive functions of CD43 expressed on colon carcinoma cells through the modulation of integrins. AB - CD43 has conflicting roles in both pro- and anti-adhesive function in cell-to cell adhesion in hematopoietic cells. We examined the role of CD43 glycoprotein in a colorectal carcinoma cell line. We expressed human CD43 antigen on HT-29 cells, a colon adenocarcinoma cell line, and compared the adhesion to the extracellular matrix with that of mock-transduced cells in vitro. CD43 expression inhibited the adhesion to extracellular matrix, such as collagen type IV and laminin. As the expression of beta1 integrin was downregulated in CD43-expressing HT-29 cells, the anti-adhesive effect of CD43 might be implicated in its expression. Our findings suggest that the anti-adhesive function of CD43 in colon carcinoma cells plays a role in the tumorigenesis and metastasis of colorectal carcinoma cells. PMID- 22075156 TI - Active biomonitoring in Greek coastal waters: application of the integrated biomarker response index in relation to contaminant levels in caged mussels. AB - An integrated approach using biomarkers and contaminant levels in mussels Mytilus galloprovincialis L. was employed to assess chemical contamination in Greek coastal waters within the framework of the MYTIMED program. Biomarkers (metallothioneins, glutathione S-transferase, catalase, acetylcholinesterase and RNA:DNA ratio) have been previously described in mussels caged at 14 sites in coastal areas influenced by different types of anthropogenic activities. This study applied a biomarker index, the Integrated Biomarker Response (IBR) to summarize biomarker responses and relate stress levels to concentrations of organochlorine compounds (PCBs, DDTs), polycyclic aromatic hydrocarbons (PAHs), and metals (Cu, Ni, Fe, Zn) measured in the mussel tissues. The IBR index indicated environmental stress at sites near cities and industries and was overall related to organic contaminants, but also elevated metal concentrations at certain sites. Slightly increased IBR values at few sites away from known pollution sources were not accompanied with increased contaminant levels suggesting stress possibly caused by natural factors. Results confirmed the usefulness of integration of biological effects measurements and chemical analysis for the assessment of chemical contamination in coastal waters. PMID- 22075157 TI - A short-term study on the interaction of bacteria, fungi and endosulfan in soil microcosm. AB - Endosulfan is one of the few organic chlorine insecticides still in use today in many developing countries. It has medium toxicity for fish and aquatic invertebrates. In this study, we added different concentrations of endosulfan to a series of soil samples collected from Baihua Park in Jinan, Shandong Province, China. Interactions of exogenous endosulfan, bacteria and fungi were analyzed by monitoring the changes in microbe-specific phospholipid fatty acids (PLFA), residual endosulfan and its metabolites which include; endosulfan sulfate, endosulfan lactone and endosulfan diol during a 9 days incubation period. Our results showed that endosulfan reduced fungi biomass by 47% on average after 9 days, while bacteria biomass increased 76% on average. In addition, we found that endosulfan degraded 8.62% in natural soil (NE), 5.51% in strepolin soil (SSE) and 2.47% in sterile soil (SE). Further analysis of the endosulfan metabolites in NE and SSE, revealed that the amount of endosulfan sulfate (ES) significantly increased and that of endosulfan lactone (EL) slightly decreased in both samples after 9 days. However, that of endosulfan diol (ED) increased in NE and decreased in SSE. After collective analysis our data demonstrated that fungi and bacteria responded differently to exogeous endosulfan, in a way that could promote the formation of endosulfan diol during endosulfan degradation. PMID- 22075158 TI - Raman spectroscopy: feasibility of in vivo survey of stratum corneum lipids, effect of natural aging. AB - The main function of the stratum corneum (SC) is for protection against external aggression. This is described as the barrier function. It mainly depends on the presence of a lipid matrix composed of ceramides, free fatty acids, cholesterol and its derivatives in the intercellular spaces. Previous studies have reported the application of Raman spectroscopy to reveal the organization of SC lipids and the state of their barrier functions. Several spectral features are directly informative about the lateral packing and the conformational order. In this work, in vivo Raman spectroscopy is used to asses the state of the SC lipid content and thus its barrier function, directly on the skin. To study the effect of natural aging on the organization of these lipids, spectra were collected from the internal side of the forearms of twenty volunteers aged from 22 to 64. Multivariate data processing enabled separation of the in vivo spectra according to the volunteers' ages. Spectral signatures show small variations, indicating a slight change in the lateral packing of SC lipids with aging of the skin. PMID- 22075159 TI - Overcoming erlotinib resistance in EGFR mutation-positive non-small cell lung cancer cells by targeting survivin. AB - Loss of PTEN was recently shown to contribute to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in EGFR mutation-positive non-small cell lung cancer (NSCLC) through activation of the protein kinase AKT. We previously showed that downregulation of the expression of the antiapoptotic protein survivin by EGFR-TKIs contributes to EGFR-TKI-induced apoptosis in EGFR mutation-positive NSCLC cells. We have now investigated the role of survivin expression in EGFR-TKI resistance induced by PTEN loss. The EGFR-TKI erlotinib did not affect survivin expression or induce apoptosis in EGFR mutation-positive NSCLC cells with PTEN loss. Downregulation of survivin either by transfection with a specific short interfering RNA or by exposure to the small-molecule survivin suppressor YM155 reversed erlotinib resistance in such cells in vitro. Furthermore, combination therapy with YM155 and erlotinib inhibited the growth of tumors formed by EGFR mutation-positive, PTEN-deficient NSCLC cells in nude mice to a greater extent than did treatment with either drug alone. These results thus indicate that persistent activation of signaling by the AKT-survivin pathway induced by PTEN loss underlies a mechanism of resistance to erlotinib-induced apoptosis in EGFR mutation-positive NSCLC. They further suggest that the targeting of survivin has the potential to overcome EGFR-TKI resistance in EGFR mutation-positive NSCLC. PMID- 22075160 TI - A monoclonal antibody against human Notch1 ligand-binding domain depletes subpopulation of putative breast cancer stem-like cells. AB - Overexpression of Notch receptors and ligands has been associated with various cancers and developmental disorders, making Notch a potential therapeutic target. Here, we report characterization of Notch1 monoclonal antibodies (mAb) with therapeutic potential. The mAbs generated against epidermal growth factor (EGF) repeats 11 to 15 inhibited binding of Jagged1 and Delta-like4 and consequently, signaling in a dose-dependent manner, the antibodies against EGF repeats 11 to 12 being more effective than those against repeats 13 to 15. These data emphasize the role of EGF repeats 11 to 12 in ligand binding. One of the mAbs, 602.101, which specifically recognizes Notch1, inhibited ligand-dependent expression of downstream target genes of Notch such as HES-1, HES-5, and HEY-L in the breast cancer cell line MDA-MB-231. The mAb also decreased cell proliferation and induced apoptotic cell death. Furthermore, exposure to this antibody reduced CD44(Hi)/CD24(Low) subpopulation in MDA-MB-231 cells, suggesting a decrease in the cancer stem-like cell subpopulation. This was confirmed by showing that exposure to the antibody decreased the primary, secondary, and tertiary mammosphere formation efficiency of the cells. Interestingly, effect of the antibody on the putative stem-like cells appeared to be irreversible, because the mammosphere-forming efficiency could not be salvaged even after antibody removal during the secondary sphere formation. The antibody also modulated expression of genes associated with stemness and epithelial-mesenchymal transition. Thus, targeting individual Notch receptors by specific mAbs is a potential therapeutic strategy to reduce the potential breast cancer stem-like cell subpopulation. PMID- 22075161 TI - New definition for periprosthetic joint infection. AB - Diagnosis of periprosthetic joint infection (PJI) remains a real challenge to the orthopedic community. Currently, there is no single standard definition for PJI. This communication presents the diagnostic criteria that have been proposed by a workgroup convened by the Musculoskeletal Infection Society. The diagnostic criteria were developed after the evaluation of available evidence. The role of every diagnostic test was examined, and the literature was reviewed in detail to determine the threshold for each test. It is hoped that the proposed definition for PJI will be adopted universally, bringing standardization into a field that has suffered extensive variability and heterogeneity. PMID- 22075162 TI - Does a high-flexion design affect early outcome of medial unicondylar knee arthroplasty? Clinical comparison at 2 years. AB - Recently, implant companies have sought to target a more active segment of the population with high-flex implants. Our aim was to compare a successful medial UKA implant with its newer high-flex version. Sixty-one patients (nonflex, 33; high-flex [HF], 28) were prospectively followed after medial UKA with a minimum of 2-year follow-up. Patients were evaluated using Short Form 12, Western Ontario and McMaster Osteoarthritis (WOMAC), Knee Society Scores, and range of motion (ROM). The HF group exhibited significantly higher WOMAC Physical Function scores at 3-month follow-up and higher WOMAC Pain and SF-12 Mental Component scores at 2 year follow-up; all other comparisons were not statistically different, including ROM. The HF cohort had significantly higher improvements in Knee Society Function and Knee score at 1- and 2-year follow-up, respectively; all other comparisons yielded no significant differences in mean improvement from baseline, including ROM or survivorship. PMID- 22075163 TI - Challenges in providing family-centered support to families in palliative care. AB - BACKGROUND: Supporting the family-as-a-whole presents challenges in palliative care, although family meetings are increasingly used in routine practice. The Family Focused Grief Therapy (FFGT) Model guides clinicians in using a range of intervention strategies. AIM: To examine the therapists' techniques used in assessing 'at risk' families in palliative care to better illuminate what helps and what remains challenging. METHOD: Recorded sessions 1 and 2 were coded using the FFGT fidelity coding measure, with its glossary of definitions. Inter-rater reliability between three coders was satisfactory at 88%. Frequencies of strategy utilization were computed, with extraction of examples of both successful and problematic approaches. SETTING/PARTICIPANTS: From within a larger study of family therapy during palliative care at a comprehensive cancer center, the first two sessions (n = 144) delivered to 74 families (299 individuals) by 32 therapists were coded and analyzed. RESULTS: Therapists readily explored the story of illness and families' ways of coping (97%) and assessed communication and cohesiveness in the majority. Exploration of relational patterns occurred in 89% of sessions, use of a genogram in 80%, understanding members' roles in 65% and family values and beliefs in 62%. Less use was made of summaries (39%), family mottos (34%), exploration of family conflict (35%) and the formalization of a comprehensive family treatment plan (20%). CONCLUSIONS: Challenges exist in therapy with difficult families. Therapy in the home brings special issues. Therapists can apply most of the interventions prescribed by the FFGT model. PMID- 22075164 TI - Qualitative evaluation of a problem-solving intervention for informal hospice caregivers. AB - BACKGROUND: Informal hospice caregivers may experience compromised well-being as a result of significant stress. Although quite limited, problem-solving interventions with this population have garnered empirical support for improved caregiver well-being. AIM: Researchers sought to answer the following question: which specific intervention processes impacted informal hospice caregivers who participated in a problem-solving intervention? DESIGN: Researchers conducted a thematic analysis of open-ended exit interviews with informal hospice caregivers who had participated in a structured problem-solving intervention. SETTING/PARTICIPANTS: Participants were friends and family members who provided unpaid care for a home hospice patient receiving services from one of two hospice agencies located in the Pacific Northwest region of the United States. RESULTS: During their participation in the problem-solving intervention, caregivers actively reflected on caregiving, structured problem-solving efforts, partnered with interventionists, resolved problems, and gained confidence and control. CONCLUSIONS: The study findings provide much needed depth to the field's understanding of problem-solving interventions for informal hospice caregivers and can be used to enhance existing support services. PMID- 22075165 TI - Nociceptive stimuli enhance anesthetic-induced neuroapoptosis in the rat developing brain. AB - Anesthetic-induced neurodegeneration in the developing brain has been well documented. However, the experiments carried out so far do not include surgical conditions. This proof of concept study was designed to investigate the impact of nociceptive stimuli on anesthetic induced neuroapoptosis in the rat developing brain. Separate cohorts of 7-day-old Sprague-Dawley rat pups were randomly assigned to six groups: Naive (room air); Anesthesia alone (70% nitrous oxide and 0.75% isoflurane for 6 h); Formalin injection alone (subcutaneous injection with 10 MUL 5% formalin into the left hind paw); Anesthesia+formalin injection; Surgical incision (to the left hind paw) alone; Anesthesia+surgical incision. Apoptosis (Caspase-3) and neuronal activation (c-Fos) in the brain and spinal cord section, and cortical TNF-alpha and IL-1beta were measured with in situ immunostaining and western blot respectively. Cognition was tested using Trace Fear conditioning 40 days after the insult. Prolonged anesthesia caused widespread apoptosis in the central nervous system compared to naive animals. Nociceptive stimulation with formalin (F) or surgical incision (S) increased the injury in the brain cortex (F: 60% or S: 40% increase) and spinal cord (F: 80% vs. S: 50% increase) respectively. Both nociceptive stimuli further augmented cognitive impairment induced by the anesthetics when assessed 40 days later. The activated pain pathway and the increased expression of the pro-inflammatory cytokine, IL-1beta, in the cortex may be responsible for the enhanced neuroapoptosis. Nociceptive stimulation and prolonged anesthesia produced significantly more apoptosis than prolonged anesthesia alone when administered to neonates during the synaptogenic period. PMID- 22075166 TI - The influence of the fungal pathogen Mycocentrospora acerina on the proteome and polyacetylenes and 6-methoxymellein in organic and conventionally cultivated carrots (Daucus carota) during post harvest storage. AB - Many carrots are discarded during post harvest cold storage due to development of fungal infections, caused by, e.g., Mycocentrospora acerina (liquorice rot). We compared the susceptibility of carrots grown under conventional and organic agricultural practices. In one year, organically cultivated carrots showed 3* to 7* more symptoms than conventionally cultivated, when studying naturally occurring disease at 4 and 6 months, respectively. On the other hand, we have developed a bioassay for infection studies of M. acerina on carrots and observed that organic roots were more susceptible after one month of storage than conventional ones, but no differences were apparent after four or six months storage. Levels of polyacetylenes (falcarinol, falcarindiol and falcarindiol-3 acetate) did not change, whereas the isocoumarin phytoalexin (6-methoxymellein) accumulated in infected tissue as well as in healthy tissue opposite the infection. The proteomes of carrot and M. acerina were characterized, the intensity of 33 plant protein spots was significantly changed in infected roots including up regulation of defence and stress response proteins but also a decrease of proteins involved in energy metabolism. This combined metabolic and proteomic study indicates that roots respond to fungal infection through altered metabolism: simultaneous induction of 6-methoxymellein and synthesis of defence related proteins. PMID- 22075167 TI - QUICK identification and SPR validation of signal transducers and activators of transcription 3 (Stat3) interacting proteins. AB - Signal transducers and activators of transcription 3 (Stat3) has been reported to be involved in the pathogenesis of various human diseases and is constitutively active in human multiple myeloma (MM) U266 cells. The Stat3-regulated mechanisms involved in these processes, however, are not fully defined. To further understand the regulation of Stat3 activity, we performed a systematic proteomic analysis of Stat3 interacting proteins in U266 cells. This analysis, termed quantitative immunoprecipitation combined with knockdown (QUICK), combines RNAi, stable isotope labeling with amino acids in cell culture (SILAC), immunoprecipitation, and quantitative MS. As a result, quantitative mass spectrometry analysis allowed us to distinguish specific Stat3 interacting proteins from background proteins and led to the identification of a total of 38 proteins. Three Stat3 interacting proteins - 14-3-3zeta, PRKCB and Hsp90 - were further confirmed by reciprocal co-immunoprecipitations and surface plasmon resonance (SPR) analysis. Our results therefore not only uncover a number of Stat3 interacting proteins that possess a variety of cellular functions, but also provide new insight into the mechanisms that regulate Stat3 activity and function in MM cells. PMID- 22075168 TI - Fibrinogen alpha chain O-glycopeptides as possible markers of urinary tract infection. AB - Urinary tract infection (UTI) is the most common bacterial infection leading to substantial morbidity and considerable health care expenditures across all ages. Here we present an exploratory UPLC-MS study of human urine in the context of febrile, complicated urinary tract infection aimed to reveal and identify possible markers of a host response on infection. A UPLC-MS based workflow, taking advantage of Ultra High Resolution (UHR) Qq-ToF-MS, and multivariate data handling were applied to a carefully selected group of 39 subjects with culture confirmed febrile Escherichia coli UTI. Using a combination of unsupervised and supervised multivariate modeling we have pinpointed a number of peptides specific for UTI. An unequivocal structural identification of these peptides, as O glycosylated fragments of the human fibrinogen alpha 1 chain, required MS2 and MS3 experiments on two different MS platforms: ESI-UHR-Qq-ToF and ESI-ion trap, a blast search and, finally, confirmation was achieved by matching experimental tandem mass spectra with those of custom synthesized candidate-peptides. In conclusion, exploiting non-targeted UPLC-MS based approach for the investigation of UTI related changes in urine, we have identified and structurally characterized unique O-glycopeptides, which are, to our knowledge, the first demonstration of O-glycosylation of human fibrinogen alpha 1-chain. PMID- 22075169 TI - Success of HPV vaccination is now a matter of coverage. PMID- 22075172 TI - Commentary on Palmyra atoll. PMID- 22075173 TI - Computational toxicology using the OpenTox application programming interface and Bioclipse. AB - BACKGROUND: Toxicity is a complex phenomenon involving the potential adverse effect on a range of biological functions. Predicting toxicity involves using a combination of experimental data (endpoints) and computational methods to generate a set of predictive models. Such models rely strongly on being able to integrate information from many sources. The required integration of biological and chemical information sources requires, however, a common language to express our knowledge ontologically, and interoperating services to build reliable predictive toxicology applications. FINDINGS: This article describes progress in extending the integrative bio- and cheminformatics platform Bioclipse to interoperate with OpenTox, a semantic web framework which supports open data exchange and toxicology model building. The Bioclipse workbench environment enables functionality from OpenTox web services and easy access to OpenTox resources for evaluating toxicity properties of query molecules. Relevant cases and interfaces based on ten neurotoxins are described to demonstrate the capabilities provided to the user. The integration takes advantage of semantic web technologies, thereby providing an open and simplifying communication standard. Additionally, the use of ontologies ensures proper interoperation and reliable integration of toxicity information from both experimental and computational sources. CONCLUSIONS: A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers. PMID- 22075174 TI - [Chromosomal translocations in soft tissue sarcomas: from molecular biology to clinical application]. AB - Recent advances in the knowledge of the molecular biology of paediatric sarcomas, especially the characterisation of chromosomal translocations associated specifically with particular types of cancer, have established bases for the introduction of new diagnostic tools. This article reviews the main chromosomal translocations associated with paediatric tumours, and summarises their molecular characteristics regarding their oncogenic capabilities, possible usefulness as a differential diagnostic tools and possible correlation with clinical parameters. PMID- 22075175 TI - Designing advanced alkaline polymer electrolytes for fuel cell applications. AB - Although the polymer electrolyte fuel cell (PEFC) is a superior power source for electric vehicles, the high cost of this technology has served as the primary barrier to the large-scale commercialization. Over the last decade, researchers have pursued lower-cost next-generation materials for fuel cells, and alkaline polymer electrolytes (APEs) have emerged as an enabling material for platinum free fuel cells. To fulfill the requirements of fuel cell applications, the APE must be as conductive and stable as its acidic counterpart, such as Nafion. This benchmark has proved challenging for APEs because the conductivity of OH(-) is intrinsically lower than that of H(+), and the stability of the cationic functional group in APEs, typically quaternary ammonia (-NR(3)(+)), is usually lower than that of the sulfonic functional group (-SO(3)(-)) in acidic polymer electrolytes. To improve the ionic conductivity, APEs are often designed to be of high ion-exchange capacity (IEC). This modification has caused unfavorable changes in the materials: these high IEC APEs absorb excessive amounts of water, leading to significant swelling and a decline in mechanical strength of the membrane. Cross-linking the polymer chains does not completely solve the problem because stable ionomer solutions would not be available for PEFC assembly. In this Account, we report our recent progress in the development of advanced APEs, which are highly resistant to swelling and show conductivities comparable with Nafion at typical temperatures for fuel-cell operation. We have proposed two strategies for improving the performance of APEs: self-cross-linking and self aggregating designs. The self-cross-linking design builds on conventional cross linking methods and works for APEs with high IEC. The self-aggregating design improves the effective mobility of OH(-) and boosts the ionic conductivity of APEs with low IEC. For APEs with high IEC, cross-linking is necessary to restrict the swelling of the membrane. In our self-cross-linking design, a short range cross-linker, tertiary amino groups, is grafted onto the quaternary ammonia polysulfone (QAPS) so that the cross-linking process can only occur during membrane casting. Thus, we obtain both the stable ionomer solution and the cross linked membrane. The self-cross-linked QAPS (xQAPS) possesses a tight-binding structure and is highly resistant to swelling: even at 80 degrees C, the membrane swells by less than 3%. For APEs with low IEC, the key is to design efficient OH(-) conducting channels. In our self-aggregating design, long alkyl side-chains are attached to the QAPS. Based on both the transmission electron microscopy (TEM) observations and the molecular dynamics (MD) simulations, these added hydrophobic groups effectively drive the microscopic phase separation of the hydrophilic and hydrophobic domains and produce enlarged and aggregated ionic channels. The ionic conductivity of the self-aggregated QAPS (aQAPS) is three fold higher than that of the conventional QAPS and is comparable to that of Nafion at elevated temperatures (e.g., greater than 0.1 S/cm at 80 degrees C). PMID- 22075170 TI - Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of study analysis of the randomised, double-blind PATRICIA trial. AB - BACKGROUND: We evaluated the efficacy of the human papillomavirus HPV-16/18 AS04 adjuvanted vaccine against non-vaccine oncogenic HPV types in the end-of-study analysis after 4 years of follow-up in PATRICIA (PApilloma TRIal against Cancer In young Adults). METHODS: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to HPV-16/18 vaccine or a control hepatitis A vaccine, via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The study was double-blind. The primary endpoint of PATRICIA has been reported previously; the present analysis evaluates cross-protective vaccine efficacy against non-vaccine oncogenic HPV types in the end-of-study analysis. Analyses were done for three cohorts: the according-to protocol cohort for efficacy (ATP-E; vaccine n=8067, control n=8047), total vaccinated HPV-naive cohort (TVC-naive; no evidence of infection with 14 oncogenic HPV types at baseline, approximating young adolescents before sexual debut; vaccine n=5824, control n=5820), and the total vaccinated cohort (TVC; all women who received at least one vaccine dose, approximating catch-up populations that include sexually active women; vaccine n=9319, control=9325). Vaccine efficacy was evaluated against 6-month persistent infection, cervical intraepithelial neoplasia grade 2 or greater (CIN2+) associated with 12 non vaccine HPV types (individually or as composite endpoints), and CIN3+ associated with the composite of 12 non-vaccine HPV types. This study is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine efficacy against CIN2+, where all cases co infected with HPV-16/18 were removed, vaccine efficacy was noted for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+ associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), with or without HPV-16/18 co-infection, was 46.8% (95% CI 30.7-59.4) in the ATP-E, 56.2% (37.2-69.9) in the TVC-naive, and 34.2% (20.4-45.8) in the TVC. Corresponding values for CIN3+ were 73.8% (48.3 87.9), 91.4% (65.0-99.0), and 47.5% (22.8-64.8). INTERPRETATION: Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV-16/18 vaccine against four oncogenic non-vaccine HPV types-HPV-33, HPV-31, HPV-45, and HPV-51-in different trial cohorts representing diverse groups of women. FUNDING: GlaxoSmithKline Biologicals. PMID- 22075171 TI - Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. AB - BACKGROUND: Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). METHODS: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85.5-100) in the TVC-naive and 45.7% (22.9-62.2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93.2% (78.9-98.7) in the TVC-naive and 45.6% (28.8-58.7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15-17 year age group and progressively decreased in the 18-20 year and 21-25 year age groups. Vaccine efficacy against all AIS was 100% (31.0-100) and 76.9% (16.0-95.8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9.0%) and 829 (8.9%) women in the vaccine and control groups, respectively; only ten events (0.1%) and five events (0.1%), respectively, were considered to be related to vaccination. INTERPRETATION: PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. FUNDING: GlaxoSmithKline Biologicals. PMID- 22075177 TI - Lichenoid skin lesions. PMID- 22075179 TI - Glutamatergic mechanisms in the dyskinesias induced by pharmacological dopamine replacement and deep brain stimulation for the treatment of Parkinson's disease. AB - Dyskinesias represent a major complication of dopamine replacement therapy in Parkinson's disease (PD) and have prompted a search for alternative treatments. The most radical advances in this field have been provided by surgical manipulations of the deep basal ganglia nuclei, and particularly by deep brain stimulation (DBS) of the subthalamic nucleus (STN). Although being very effective, high-frequency stimulation (HFS) of the STN is a poorly understood treatment. Besides its anti-akinetic activity, it can be pro-dyskinetic above a certain stimulation intensity. Accumulating evidence indicates that dyskinesias induced by STN-HFS and dopamine replacement therapy are linked to dysregulation of glutamate transmission in the basal ganglia. In rat models of PD, both types of dyskinesia are associated with increased concentrations of extracellular glutamate and altered expression of glutamate transporters in the substantia nigra pars reticulata and the striatum. Furthermore, a vast and ever growing literature has revealed changes in the expression, phosphorylation state, and/or subcellular distribution of specific subtypes of glutamate receptors in these dyskinetic conditions. Both types of dyskinesias are linked to an increased phosphorylation of NR2B-containing NMDA receptors in critical basal ganglia circuits. We conclude that disruption of glutamate homeostasis and activation of perisynaptic and extra-synaptic glutamate receptors are an important pathophysiological component of these treatment-induced dyskinesias in PD. These findings lay the ground for therapeutic development initiatives targeting dysfunctional components of glutamate transmission in the basal ganglia. PMID- 22075180 TI - Platelet-leukocyte interactions in thrombosis. AB - Activated platelets may adhere to leukocytes and form circulating mixed aggregates. The latter are considered a reliable marker of a prothrombotic state and are associated with several cardiovascular conditions. The molecular mechanisms responsible of this cellular interaction include a central role of platelet P-selectin and of P-selectin glycoprotein ligand-1 (PSGL-1), its counter receptor on leukocytes in a signaling cascade, resulting in the activation of the beta-2 integrin Mac-1 and in the firm adhesion between the two cell types. The interaction of P-selectin with PSGL-1 also induces upregulation of leukocyte tissue factor, biosynthesis of several cytokines and other inflammatory reactions, thereby contributing to the thrombotic progression. In this review the main determinants of mixed aggregate formation, the heritability component, the major pathological conditions associated with higher levels of mixed aggregates in the circulation will be discussed. Besides current anti-platelet or antithrombotic drugs, natural compounds, such as the polyphenols present in vegetable foods and red wine, have been tested for their inhibitory effect on mixed aggregate formation. The promising results shown by studies in vitro and in experimental animal models, remain to be carefully investigated in humans. Platelet-leukocyte aggregates provide a novel link between inflammation and thrombosis, two central processes in atherogenesis. A better understanding of the role of platelet-leukocyte interactions in athero-thrombosis will be instrumental for the progress of prevention and treatment of ischaemic cardiovascular disease. PMID- 22075181 TI - Parkinson's disease and pathological oscillatory activity: is the beta band the bad guy? - New lessons learned from low-frequency deep brain stimulation. AB - A number of studies have identified pathological neural oscillations in Parkinson's disease and it is widely agreed that these excessive synchronizations are linked to the motor symptoms of Parkinson's disease (PD). However, it is still under debate if there exists a single frequency having a critical negative influence on PD symptoms and what this frequency might be. To provide experimental evidence for a causal link between beta oscillations and bradykinesia, C. C. Chen and coauthors stimulated patients with Parkinson's disease with different low frequencies while the patients were performing a grip force task [C. C. Chen, W. Y. Lin, H.L. Chan, Y.T. Hsu, P.H. Tu, S.T. Lee, S.M. Chiou, C.H. Tsai, C.S. Lu, P. Brown: Stimulation of the subthalamic region at 20 Hz slows the development of grip force in Parkinson's disease, Exp. Neurology, 2011]. In their study the authors could demonstrate a 15% slowing in the grip force task during 20 Hz stimulation, but not during stimulation with other frequencies. The finding of 20 Hz being the driving pathological frequency contrasts with previous studies using e.g. finger tapping, where 5 and 10 Hz had the largest influence. Thus, this study provides evidence that there is no single pathological oscillation frequency that is responsible for all Parkinsonian symptoms. Instead, the results indicate that the modulation of very specific frequencies leads to changes in specific performance parameters evaluated in particular tasks. In this respect, this study also provides more physiological evidence on the involvement of the STN in dynamic force production. Taken together, the study adds a further piece to the puzzle of understanding the pathophysiology of Parkinson's disease and the mechanisms of deep brain stimulation. PMID- 22075182 TI - The systems biology of neurofibromatosis type 1--critical roles for microRNA. AB - Neurofibromatosis type 1 (NF1) is one of the most common inherited neurological disorders with a wide range of clinical manifestations. The causative gene for NF1 encodes a multi-domain protein, neurofibromin, which interacts with RAS through its RAS-GAP domain. Dysfunction of neurofibromin results in abnormal RAS activation in the cells which has been thought to be the main process in the initiation and progression of NF1. Based on this hypothesis, inhibitors for various RAS mediated signaling pathways are in different stages of clinical trials to treat NF1 or NF1-associated symptoms. While the molecular genetics of NF1 has made significant progress in recent years, the underlying etiology and progression of NF1 are yet to be fully understood. Besides review and summarization of the latest results of genetic, transcriptomic and microRNA studies associated with NF1, we conducted limited post-hoc analysis to illustrate the importance of using integrated systems biology approach to study complex diseases like NF1. PMID- 22075183 TI - Letter to the editor. PMID- 22075185 TI - Challenges of supplementary treatment for neurodegenerative diseases. PMID- 22075184 TI - A perfusion-metabolic mismatch in Sturge-Weber syndrome: a multimodality imaging study. AB - OBJECTIVE: We combined perfusion weighted imaging (PWI) with 2-deoxy 2[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) to study the relationship between regional metabolic and perfusion abnormalities and their clinical correlates in children with Sturge-Weber syndrome (SWS). METHODS: Fifteen children (age: 0.9-10 years) with unilateral SWS underwent high resolution PWI and FDG PET prospectively. Regional (lobar) asymmetry indices (AIs) of subcortical white matter (WM) cerebral blood flow (CBF) were correlated with corresponding cortical FDG uptake asymmetries, extent of leptomeningeal vascular malformation and clinical seizure variables. RESULTS: Abnormal cortical glucose metabolism and/or subcortical WM CBF were seen in all lobes affected by vascular malformation and extended to lobes not affected by abnormal pial vessels in 6 patients. Lower CBF was associated with lower cortical glucose metabolism in the temporal, parietal and occipital lobes (p<=0.02). While decreased perfusion was associated with hypometabolism in most cases, increased regional CBF (found in 6 patients) was commonly associated with relatively mild or no hypometabolism. Ten of 24 cerebral lobes with normal glucose metabolism in the affected hemisphere showed abnormal perfusion. High seizure frequency was associated with severe parieto-occipital hypoperfusion (p<=0.03), while long duration of epilepsy was related to frontal lobe hypometabolism (p=0.015). CONCLUSIONS: Regional perfusion and cortical metabolic abnormalities can extend beyond lobes affected by leptomeningeal vascular malformations and are related to epilepsy in SWS. Despite a general correlation between perfusion and metabolism, increased WM perfusion with preserved cortical metabolism in overlying cortex is a common pattern of a perfusion/metabolic mismatch. This may represent a disease stage where cortical function is preserved while increased WM perfusion provides collateral drainage of cortex via the deep vein system. PMID- 22075186 TI - Transcriptional analysis of human papillomavirus type 16 in histological sections of cervical dysplasia by in situ hybridisation. AB - BACKGROUND: The HPV-16 virus is well described as a causative agent in cervical cancer. AIMS: To individually analyse the transcription profile of the HPV-16 viral genes in patient biopsies of varying grades of cervical dysplasia by a chromogenic in situ hybridisation technique. METHODS: 19 formalin fixed, paraffin embedded (FFPE) biopsies of cervical dysplasia were analysed by a chromogenic in situ hybridisation protocol using novel long single stranded digoxigenin labelled DNA probes targeted to the individual HPV-16 gene RNAs. RESULTS: A transcription pattern for all the HPV-16 genes that is always conserved to the upper intermediate and superficial layers of the cervical epithelium and is independent of the level of dysplasia is described. E1 and E6 transcripts were found to express with a uniquely nuclear localisation; all other transcripts had both nuclear and cytoplasmic localisation. E5 oncogene transcripts were abundant in all cases, being equal to or greater than E7. Deep investigation of the E2 RNA transcript showed a potential alternative transcript with a possible novel start codon. CONCLUSIONS: This data represents new information on HPV-16 viral transcription events that bring into question some of the current beliefs on the mechanism of HPV-16 infection in the progression to cervical cancer. Results support high expression of the E5 and E7 oncogenes in cervical dysplasias infected by HPV-16 in contrast to the low levels identified for the E6 oncogene and a possible alternative transcript for the E2 gene. The diagnostic utility of the detection of HPV-16 RNA transcripts is becoming more apparent and a renewed look at their in situ localisation in cervical biopsies could be beneficial. PMID- 22075187 TI - Validity of internal expression of the major histocompatibility complex class I in the diagnosis of inflammatory myopathies. AB - OBJECTIVE: The inflammatory myopathies (IMs) are a group of disorders characterised by weakness and inflammation of the skeletal muscles. Muscle biopsy is the most crucial test to confirm the clinical diagnosis, but also the most common cause of misdiagnosis. There are currently no markers specific or sensitive enough to distinguish IMs from other diseases with similar clinical and morphological features, and an international multidisciplinary effort is under way to develop new classification criteria for IMs. METHODS: Standards for Reporting of Diagnostic Accuracy recommendations to validate a diagnostic test based on the quantification of internal major histocompatibility complex class I (MHC-I) positive fibres were adopted. MHC-I immunostained specimens from 64 patients were scored by two independent blinded investigators, and the percentage of positive fibres was determined. Agreement between investigators was evaluated with the k-weighted statistic. The receiver operating characteristic curve, area under the curve, sensitivity, specificity, and positive and negative predictive values of each percentage range of positive fibres versus the diagnosis of IM were calculated. RESULTS: The main difference between IM and non-inflammatory samples was the number of internal MHC-I positive fibres. The k-weighted value was 0.89 for a percentage of MHC-I positive fibres above 50%; the positive predictive value was 100%, and the negative predictive value was 94%. CONCLUSIONS: This is the first study on the validity of a quantitative analysis of internal MHC-I positive fibres for an IM diagnosis performed according to Standards for Reporting of Diagnostic Accuracy recommendations. The interobserver agreement was almost perfect, thus making the method reproducible. Applying an MHC-I cut-off above 50% is an optimal marker for polymyositis (PM) and dermatomyositis (DM) diagnosis. PMID- 22075188 TI - Pathology of primary and metastatic mucinous ovarian neoplasms. AB - Recent years have seen a dramatic change in the pathological approach to ovarian mucinous neoplasms. A substantial proportion of tumours previously considered to be ovarian primaries actually represent secondary ovarian involvement by tumours elsewhere in the body. Two major categories of tumour have completely disappeared from the diagnostic spectrum: ovarian 'borderline' mucinous tumour associated with pseudomyxoma peritonei, and widely disseminated mucinous carcinomas. The emergent picture of true ovarian primary carcinoma of pure mucinous morphology is that this is a rare malignancy that is low grade and low stage at presentation in the vast majority of cases, with a very low likelihood of aggressive clinical behaviour. A large volume of literature has appeared concerning the pathological distinction of primary from metastatic ovarian mucinous neoplasms in view of the dramatically different prognosis and treacherously similar morphology. Clinicopathological parameters useful in the distinction of primary from metastatic mucinous ovarian carcinomas are reviewed. Major features favouring metastases are bilaterality, size <10 cm, surface involvement, extensive intra abdominal spread and an extensive infiltrative pattern with desmoplasia. Two morphological patterns essentially exclude ovarian origin: colloid and signet ring carcinomas. Features favouring primary ovarian origin are unilaterality, large size >12 cm, smooth external surface and association with other ovarian pathology. An admixture of benign, borderline and malignant patterns in the same tumour favour primary origin, but can be misleading as a 'maturation' pattern in metastases can result in the same appearance. PMID- 22075189 TI - [Role of angioplasty in the treatment of renal artery stenosis]. AB - Atherosclerotic renal artery stenosis is frequent and is associated with a high incidence of morbidity and mortality, with a strong correlation with coronary artery disease, (Kalra et al., 2005; Cheung et al., 2002; Guo et al., 2007 [1 3]). The atherosclerotic renal artery stenosis is an independent predictive factor of death (Conlon et al., 1998 [4]). The treatment of this lesion does not have strong evidence. A lot of studies in this area suggest the angioplasty is superior in a big majority between surgery, and angioplasty with stent is superior between balloon angioplasty, but some studies fail to prove the superiority of angioplasty versus medical treatment. These studies have sadly a lot of mistakes and nowadays we don't know what is the treatment for our patients in a lot of cases. The angioplasty is indicated when there is a failure of antihypertensive medications for control of blood pressure, when it is associated with a renal insufficiency quickly progressive or when there is a lesion on each renal artery. Other studies must be organized for prove the superiority of angioplasty when there is a real stenosis, maybe with the use of fractional flow reserve. PMID- 22075190 TI - [Successes and complications of angioplasty in chronic occlusive coronary disease]. AB - In the hands of experienced operators, the rate of success of percutaneous coronary intervention for chronic total occlusion lesion is about 85%. Major cardiac events rate is about 2%. A length of the occluded site more than 20mm, severe calcifications, major tortuosity, blunt stump and a previous attempt by anterograde approach are predictors of procedural failure, previous CABG, distal vessel disease, occlusion duration have been involved too. Operator's experience is one of the major success component, especially his ability to perform retrograde approach. According to EuroCTO club recommendations, performing a minimum number of case to maintain competency seems to be very important. PMID- 22075191 TI - [Mortality of myocardial infarction]. AB - Coronary disease is a major cause of death and disability. From 1975 to 2000, coronary mortality was reduced by half. Better treatments and reduction of risk factors are the main causes. This phenomenon is observed in most developed countries, but mortality from coronary heart disease continues to increase in developing countries. In-hospital mortality of ST elevation myocardial infarction (STEMI) is in the range of 7 to 10% in registries. In infarction without ST segment elevation (NSTEMI), in-hospital mortality is around 5%. More recent studies found a similar in-hospital mortality for STEMI and NSTEMI. Because of patient selection and monitoring, mortality in clinical trials is much lower. After adjustment for the extent of coronary disease, age, risk factors, history of myocardial infarction, the excess mortality observed in women is fading. Many clinical, biological and laboratory parameters are associated with mortality in myocardial infarction. They refer to the immediate risk of death (ventricular rhythm disturbances, shock...), the extent of infarction (number of leads with ST elevation on the ECG, release of biomarkers, ejection fraction...), the presence of heart failure, the failure of reperfusion and the patient's baseline risk (age, renal function...). Risk scores, and more specifically the GRACE risk score, synthesize these different markers to predict the risk of death in a given patient. However, their use for the treatment of myocardial only concerns NSTEMI. Only a limited number of mechanical or pharmacological interventions reduces mortality of heart attack. The main benefits are observed with reperfusion by thrombolysis or primary angioplasty in STEMI, aspirin, heparin, beta-blockers, angiotensin converting enzyme inhibitors. Some medications such as bivalirudin and fondaparinux reduce mortality by decreasing the incidence of hemorrhagic complications. The guidelines classify interventions according to their benefit and especially their ability to reduce mortality. Organized care systems that improve implementation of guidelines also reduce mortality. Finally, some new therapeutic approaches such as post-conditioning and new therapeutic classes offer encouraging prospects for further reducing the mortality of myocardial infarction. PMID- 22075192 TI - Guidewire biliary cannulation does not reduce post-ERCP pancreatitis compared with the contrast injection technique in low-risk and high-risk patients. AB - BACKGROUND: Guidewire (GW) cannulation can reduce the risk of post-ERCP pancreatitis (PEP) by avoiding the opacification of the main pancreatic duct. OBJECTIVE: To compare the effects of conventional contrast ERCP and GW cannulation of the common bile duct on the rate of PEP in low- and high-risk patients. DESIGN: Prospective, comparative-intervention single-center study. SETTING: Tertiary referral center. PATIENTS: Patients with biliary disease with an intact papilla were prospectively examined by ERCP. INTERVENTIONS: Biliary cannulation using a sphincterotome with contrast injection (ConI) or a hydrophilic GW without contrast injection. MAIN OUTCOME MEASUREMENTS: Pancreatitis rate in the GW group and the contrast injection (ConI) group. RESULTS: PEP occurred in 60 of 1249 patients (4.8%), 35 of 678 (5.2%) in the GW group and 25 of 571 (4.4%) in the ConI group (not significant). The overall rate of PEP was significantly higher in high-risk patients (12.2%) than in low-risk patients (3.5%) (P < .001), but was similar for the 2 techniques within each of these 2 groups. In patients with unintended main pancreatic duct (MPD) cannulation or opacification, the rate of PEP was not significantly different with the GW (15.2%) and ConI (8.4%) techniques but was associated with a significantly higher rate of pancreatitis (11.9%) than in patients in whom the contrast medium or GW did not enter the MPD (3.5%) (P < .001). Multivariate analysis indicated that more than 10 papillary cannulation attempts, MPD cannulation or opacification, suspected sphincter of Oddi dysfunction, and precut methods were significant risk factors independently associated with PEP. LIMITATIONS: Lack of randomization. CONCLUSIONS: For selective cannulation of the CBD, the risk of inducing PEP is similar with the ConI and GW techniques in high risk and low-risk patients. Any manipulation of the MPD must be considered a high risk factor for PEP, such as multiple attempts on the papilla or use of the precut method. PMID- 22075193 TI - A kinematic method for footstrike pattern detection in barefoot and shod runners. AB - Footstrike patterns during running can be classified discretely into a rearfoot strike, midfoot strike and forefoot strike by visual observation. However, the footstrike pattern can also be classified on a continuum, ranging from 0% to 100% (extreme rearfoot to extreme forefoot) using the strike index, a measure requiring force plate data. When force data are not available, an alternative method to quantify the strike pattern must be used. The purpose of this paper was to quantify the continuum of foot strike patterns using an easily attainable kinematic measure, and compare it to the strike index measure. Force and kinematic data from twenty subjects were collected as they ran across an embedded force plate. Strike index and the footstrike angle were identified for the four running conditions of rearfoot strike, midfoot strike and forefoot strike, as well as barefoot. The footstrike angle was calculated as the angle of the foot with respect to the ground in the sagittal plane. Results indicated that the footstrike angle was significantly correlated with strike index. The linear regression model suggested that strike index can be accurately estimated, in both barefoot and shod conditions, in the absence of force data. PMID- 22075194 TI - Rheumatic manifestations of cancer. AB - Taken together, the wide range of rheumatic and musculoskeletal conditions that can appear in association with cancer emphasizes that rheumatic disease is a major component of the spectrum of paraneoplastic manifestations. Although the pathogenetic mechanisms by which neoplasia causes these manifestations are only partially understood in select cases, it appears that many result from immune mediated effects stimulated by tumor antigens of endocrine factors produced by tumors. The broad overlap in signs and symptoms of occult malignancy and systemic rheumatic disease, as well as the occurrence of distinct localized and systemic musculoskeletal and rheumatic syndromes in the presence of cancer, emphasizes the importance of considering and investigating the possibility of occult malignancy in the evaluation of patients with these symptoms. This is particularly important in older patients, those with atypical rheumatic disease, and those who do not respond appropriately to conventional immunosuppressive therapy. PMID- 22075196 TI - Rheumatic manifestations of primary and metastatic bone tumors and paraneoplastic bone disease. AB - Bone tumors can show a wide range of nonspecific rheumatic manifestations. The presence of unexplained or atypical chronic bone pain, an enlarging bone mass, neurovascular compression syndromes, or pathologic fractures should alert us to the possibility of a bone tumor causing these symptoms. These patients must undergo a complete physical examination; adequate imaging; and, if needed, a biopsy to confirm their diagnosis and offer them an opportune treatment. In addition, bone tumors and other malignancies can present remote clinical manifestations and unusual laboratory findings (eg, HOA, hypophosphatemia, hyperphosphaturia, and hypercalcemia) that may be the first and early manifestation of an occult cancer. These findings should motivate a cancer screening according to age, sex, and personal history. Cancer therapies also have a big impact on bone health, increasing the risk of osteoporosis, osteomalacia, and/or osteonecrosis. Rheumatologists should be aware of possible long-term adverse events of cancer treatment to avoid future complications. PMID- 22075195 TI - Serologic laboratory findings in malignancy. AB - Autoantibodies are extremely promising diagnostic and prognostic biomarkers of cancer, and have the potential to promote early diagnosis and to make a large impact by improving patient outcome and decreasing mortality. Moreover, autoantibodies may be useful reagents in the identification of subjects at risk for cancer, bearing premalignant tissue changes. Great efforts are being made in many laboratories to validate diagnostic panels of autoantibodies with high sensitivity and specificity that could be useful in a clinical setting. It is likely that prospective studies of sufficiently large cohorts of patients and controls using high-throughput technology may allow the identification of biomarkers with diagnostic significance, and perhaps of discrete antigen phenotypes with clinical significance. The identification of TAAs may also be essential for the development of anticancer vaccines, because autoantibodies found in cancer sera target molecules involved in signal transduction, cell-cycle regulation, cell proliferation, and apoptosis, playing important roles in carcinogenesis. On this basis, molecular studies of antigenantibody systems in cancer promise to yield valuable information on the carcinogenic process. TAAs identified by serum antibodies in cancer sera can be natural immunogenic molecules, useful as targets for cancer immunotherapy. An important problem encountered in the practice of medicine is the identification of healthy individuals in the general population who unknowingly are at high risk of developing cancer. For the rheumatologist, a related problem is the identification of those patients with rheumatic diseases who are at high risk for developing a malignant process. These problems encountered in the fields of cancer and the rheumatic diseases can in the future be helped by new diagnostic instruments based on antibodies. The need for promoting the early diagnosis of cancer is a recognized major public health problem in need of significant research support for the validation of multiple promising but inconclusive studies, with the intention of producing diagnostic panels of autoantibodies in various types of cancers. Cancer developing in patients with rheumatic diseases is also an important problem requiring prospective longterm follow-up studies of patients with rheumatic diseases, particularly because some of the new biologic therapies seem to increase the cancer risk. It is possible that a panel of autoantibodies common to patients with cancer and the rheumatic diseases may prove to be of value in the identification of those patients with ADs at high risk for neoplasms. PMID- 22075197 TI - Neoplastic and paraneoplastic synovitis. AB - Arthritis is a common finding in patients who have cancer. In this population, it is crucial to rule out septic arthritis and metastatic synovitis. Culture, crystallography, (table see text) and cytology of synovial fluid are useful initial diagnostics tools. If all are negative, histopathology of synovial tissue should be considered. Crystal synovitis is another frequent cause of arthritis in patients who have cancer, but it can also coexist with other conditions such as septic arthritis. Independent rheumatic disorders, drug-induced arthritis, and paraneoplastic syndromes should be considered after the exclusion of sepsis and metastatic disease. The diagnosis of a paraneoplastic syndrome is easier when the malignancy is evident or typical findings such as HOA or palmar fasciitis are present. However, these paraneoplastic phenomena can occur before the cancer diagnosis, and it is important to be aware of the association of these conditions with an underlying tumor. Rheumatic disorders with atypical clinical presentation in older patients, poor response to usual treatment, systemic features such as weight loss, and clinical findings compatible with well recognized paraneoplastic syndromes should alert clinicians to the possible coexistence of an occult malignancy. PMID- 22075198 TI - Neoplastic/paraneoplastic dermatitis, fasciitis, and panniculitis. AB - The skin changes outlined in this article can be important clues to an underlying malignancy. Paraneoplastic dermatoses are skin disorders associated with an underlying neoplasm and whose course parallels that of the neoplasm. Recognizing these skin presentations leads to early diagnosis and management of the underlying malignancy. Effective treatment of the associated neoplasm often leads to improvement of the cutaneous manifestations and should be the primary focus of each patient's management. PMID- 22075199 TI - Neoplastic and paraneoplastic vasculitis, vasculopathy, and hypercoagulability. AB - It is essential to be aware of both neoplastic and paraneoplastic vasculitides, vasculopathy, and hypercoagulability, considering the importance of an accurate diagnosis and timely treatment of the underlying malignancy. Characteristics such as the type of vasculitis, age, gender, atypical presentation, and lack of response to common therapies should prompt investigation for an occult malignancy, whereas vasculitis such as GPA require due malignancy vigilance given a significantly increased risk of malignancy at the time of diagnosis and in the following years. Vasculopathies are rarer than vasculitides, but are associated with specific malignancies and, in the context of such malignancies, should be kept in mind. Hypercoagulability is a well-documented neoplastic phenomenon with an increased risk of thrombosis in the setting of positive aPLs. Most neoplastic and paraneoplastic vascular syndromes require no specific treatment outside of treatment of the underlying malignancy. The two key exceptions are PACNS, because of its poor prognosis, and erythromelalgia, in which aspirin is an effective agent. PMID- 22075200 TI - Paraneoplastic myalgias and myositis. AB - There are several key observations on paraneoplastic myopathies: The risk of cancer associated with DM is very high, whereas risk of cancer associated with PM is mildly increased Most cancers develop within one year of the onset of myositis, although the risk remains high up to 5 years after diagnosis. The most common cancers associated with DM are adenocarcinoma, including lung, ovary, cervical, stomach, pancreas, colorectal and lymphoma, whereas PM is associated with a high risk of lymphoma. The clinical course of myopathy is closely linked with the course of cancer. Certain clinical features are associated with CAM including severe treatment resistant skin manifestations, severe muscle weakness, respiratory muscle weakness, and dysphagia, while some clinical features are protective such as arthritis, Raynaud, and ILD. Screening should be based on age, gender, ethnicity, and the geographic area of the patient; however, certain high risk patients may require more extensive screening including tumor markers and thoracoabdominal-pelvic CT scans. Certain autoantibodies including anti-p155 and the absence of more common autoantibodies are associated with a higher risk of CAM, while the presence of antisynthetase autoantibodies lowers the risk for CAM. Although the pathogenesis of CAM is unclear, a plausible hypothesis is that immune responses generated against antigens commonly targeted in myositis are related to antitumor responses in affected individuals. PMID- 22075201 TI - Neoplasm mimics of rheumatologic presentations: sialadenitis, ocular masquerade syndromes, retroperitoneal fibrosis, and regional pain syndromes. AB - IgG4-RSD should be suspected in any patient presenting with lacrimal or salivary gland enlargement, particularly if male and manifesting mild glandular dysfunction. A serum IgG4 level, if increased, may be helpful, although a gland biopsy staining for IgG4-positive plasma cells is the definitive test. Primary low-grade B cell lymphomas of the glandular tissue, specifically MALT lymphoma and other glandular malignancy, should be considered, particularly in patients with asymmetric glandular enlargement. Patients with idiopathic uveitis should have a thorough evaluation to exclude malignancy, in particular PIOL and melanoma in adults, and diffuse retinoblastoma and ALL in children. RF remains a diagnostic challenge and atypical features such as outward displacement of the retroperitoneal structures should raise the suspicion for a malignant infiltrative process. CRPS rarely may be the first presentation of an occult malignancy and requires a thorough review of age-appropriate cancer screening. Carpal tunnel syndrome, if bilateral or associated with other systemic features, should prompt a search for amyloidosis. PMID- 22075202 TI - Paraneoplastic and cancer treatment-related rheumatic disorders. PMID- 22075204 TI - Alexithymia in relation to parental alcoholism, everyday frontal lobe functioning and alcohol consumption in a non-clinical sample. AB - BACKGROUND: Recent studies have indicated that 45-67% of those in treatment for alcohol use disorders suffer from alexithymia, a multifaceted personality trait characterized by difficulties identifying and describing emotions and an externally oriented cognitive style. The high reported prevalence rates of alexithymia among those with alcohol dependence led to speculation that alexithymia is a personality dimension that may predispose to risky or problematic alcohol use. METHODS: This notion was examined in 314 adult volunteers (54% female) aged 18-45 years (M=27.6 years), all of whom reported at least occasional alcohol consumption, who completed online surveys assessing alexithymia (Toronto Alexithymia Scale, or TAS-20), parental alcoholism (Children of Alcoholics Screening Test, or CAST), everyday signs of frontal lobe dysfunction (Frontal Systems Behavior Scale, or FrSBe) and risky alcohol use (Alcohol Use Disorders Identification Test, or AUDIT). RESULTS: TAS-20 scores were positively correlated with the index of parental alcoholism CAST, index of frontal lobe dysfunction FrSBe and measure of alcohol-related problems AUDIT. Chi square test showed an association between TAS-20-defined alexithymia and being the offspring of an alcoholic parent as defined by CAST. Regression analysis showed that frontal lobe dysfunction (FrSBe) mediated the relationship between alexithymia (TAS-20 total score) and risky alcohol use (AUDIT). CONCLUSIONS: The findings suggest that alexithymia is related to deficiencies in frontal lobe functioning that may reflect a heritable predisposition to alcohol problems. PMID- 22075206 TI - Intracellular metabolic pathways control immune tolerance. AB - Disorders such as obesity and type 2 diabetes have been linked to immune dysfunction, raising the possibility that metabolic alterations can be induced by or be a consequence of alterations in immunological tolerance. Here, we describe how intracellular metabolic signalling pathways can 'sense' host energy/nutritional status, and in response, modulate regulatory T (Treg) cell function. In particular, we focus on mammalian target of rapamycin (mTOR) signalling, and how stimuli such as nutrients and leptin activate mTOR in an oscillatory manner to determine Treg cell proliferation status. We propose that metabolic changes such as nutritional deprivation or overload could dictate the characteristics of the Treg cell compartment and subsequent downstream immune reactions. PMID- 22075205 TI - Regulation of endocannabinoid release by G proteins: a paracrine mechanism of G protein-coupled receptor action. AB - In the past years, the relationship between the endocannabinoid system (ECS) and other hormonal and neuromodulatory systems has been intensively studied. G protein-coupled receptors (GPCRs) can stimulate endocannabinoid (eCB) production via activation of G(q/11) proteins and, in some cases, G(s) proteins. In this review, we summarize the pathways through which GPCR activation can trigger eCB release, as well as the best known examples of this process throughout the body tissues. Angiotensin II-induced activation of AT(1) receptors, similar to other G(q/11)-coupled receptors, can lead to the formation of 2-arachidonoylglycerol (2 AG), an important eCB. The importance of eCB formation in angiotensin II action is supported by the finding that the hypertensive effect of angiotensin II, injected directly into the hypothalamic paraventricular nucleus of anaesthetized rats, can be abolished by AM251, an inverse agonist of CB(1) cannabinoid receptors (CB(1)Rs). We conclude that activation of the ECS should be considered as a general consequence of the stimulation of G(q/11)-coupled receptors, and may mediate some of the physiological effects of GPCRs. PMID- 22075207 TI - E4BP4: an unexpected player in the immune response. AB - Until recently, the basic leucine zipper transcription factor E4BP4 (also known as NFIL3) was of little interest to immunologists, being best known for its role in regulating circadian rhythm in chick pineal gland. However, characterisation of E4bp4(-/-) mice, independently generated in four different laboratories, has revealed roles for E4BP4 in diverse haematopoietic lineages. E4BP4 is essential for the development of NK cells and CD8alpha(+) conventional dendritic cells, and is also involved in macrophage activation, polarisation of CD4(+) T cell responses and B cell class switching to IgE. Here, we discuss the role of E4BP4 as a regulator of the immune response and highlight future questions for the field. PMID- 22075209 TI - Determinants of relative skeletal maturity in South African children. AB - The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (p<0.01) and heavier at 2 years (p<0.01) predicted less delay in RSM at age 9/10 years, independent of current size and body composition. In females, both height at 2 years and conditional weight at 2 years predicted less delay in RSM at 9/10 years (p<0.05) but this effect was mediated by current body composition. Having greater lean mass at 9/10 years was associated with less delayed RSM in females (p<0.01) as was pubertal status at the time of skeletal maturity assessment (p<0.01). This study identifies several predictors of skeletal maturation at 9/10 years, indicating a role for early life exposures in determining the rate of skeletal maturation during childhood independently of current stature. PMID- 22075208 TI - Sost downregulation and local Wnt signaling are required for the osteogenic response to mechanical loading. AB - Sclerostin, the Wnt signaling antagonist encoded by the Sost gene, is secreted by osteocytes and inhibits bone formation by osteoblasts. Mechanical stimulation reduces sclerostin expression, suggesting that osteocytes might coordinate the osteogenic response to mechanical force by locally unleashing Wnt signaling. To investigate whether sclerostin downregulation is a pre-requisite for load-induced bone formation, we conducted experiments in transgenic mice (TG) engineered to maintain high levels of SOST expression during mechanical loading. This was accomplished by introducing a human SOST transgene driven by the 8 kb fragment of the DMP1 promoter that also provided osteocyte specificity of the transgene. Right ulnae were subjected to in vivo cyclic axial loading at equivalent strains for 1 min/day at 2 Hz; left ulnae served as internal controls. Endogenous murine Sost mRNA expression measured 24 h after 1 loading bout was decreased by about 50% in TG and wild type (WT) littermates. In contrast, human SOST, only expressed in TG mice, remained high after loading. Mice were loaded on 3 consecutive days and bone formation was quantified 16 days after initiation of loading. Periosteal bone formation in control ulnae was similar in WT and TG mice. Loading induced the expected strain-dependent increase in bone formation in WT mice, resulting from increases in both mineralizing surface (MS/BS) and mineral apposition rate (MAR). In contrast, load-induced bone formation was reduced by 70-85% in TG mice, due to lower MS/BS and complete inhibition of MAR. Moreover, Wnt target gene expression induced by loading in WT mice was absent in TG mice. Thus, downregulation of Sost/sclerostin in osteocytes is an obligatory step in the mechanotransduction cascade that activates Wnt signaling and directs osteogenesis to where bone is structurally needed. PMID- 22075210 TI - Receptor activator of NF-kappaB ligand-dependent expression of caveolin-1 in osteoclast precursors, and high dependency of osteoclastogenesis on exogenous lipoprotein. AB - Although extensive studies have done much to clarify the molecular mechanisms of osteoclastogenesis during the last ten years, there may still be unknown molecules associated with osteoclast differentiation. Thus, we used fluorescent differential display to screen for genes whose expression is induced by receptor activator of NF-kappaB ligand (RANKL), a crucial molecule for osteoclast formation. We identified caveolin-1 (Cav-1) as a RANKL-induced gene. Cav-1 is a major structural protein of caveolae and lipid rafts, cholesterol-enriched microdomains in the plasma membrane (PM). The RANKL-induced Cav-1 was immediately conveyed to lipid rafts. Conversely, expression of flotillin-1 (Flot-1), another scaffolding protein of lipid rafts, was reduced during osteoclastogenesis, indicating conversion of Flot-1-predominant rafts into Cav-1-enriched rafts. However, in vitro osteoclastogenesis of precursor cells from Cav-1-null mice was comparable to that of wild-type mice, while Cav-2 expression in the knockout osteoclasts was maintained. Conversely, Cav-2 gene silencing in Cav-1-null osteoclast precursors using siRNA for Cav-2 increased osteoclast formation, suggesting that the Cav-1/Cav-2 complex may act as a negative regulator for osteoclastogenesis. On the other hand, destruction of lipid rafts by removal of cholesterol from the PM by methyl-beta-cyclodextrin (MCD) treatment caused disordered signal transductions for osteoclastogenesis, such as hyperactivation of Erk1/2 and insensitivity of Akt to RANKL stimulus. The abnormal signaling was reproduced by deleting exogenous lipoproteins from the culture medium, which also resulted in reduced osteoclast formation. In addition, the deletion caused delayed expression of nuclear factor of activated T cells c1 (NFATc1), and depressed its activation in the cytosol and inhibited its translocation into nuclei. Simultaneously, the deletion reduced the level of FcRgamma, a trigger protein for initiating the calcium signaling needed to activate NFATc1, and decreased Cav-1 in lipid rafts. These findings indicate that the molecular mechanisms of osteoclastogenesis are highly dependent on extracellular lipoprotein and the integrity of lipid rafts, and suggest possible involvement of cholesterol. PMID- 22075211 TI - Variability of protein level and phosphorylation status caused by biopsy protocol design in human skeletal muscle analyses. AB - BACKGROUND: Bergstrom needle biopsy is widely used to sample skeletal muscle in order to study cell signaling directly in human tissue. Consequences of the biopsy protocol design on muscle protein quantity and quality remain unclear. The aim of the present study was to assess the impact of different events surrounding biopsy protocol on the stability of the Western blot signal of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, glycogen synthase kinase-3beta (GSK-3beta), muscle RING finger protein 1 (MuRF1) and p70 S6 kinase (p70 S6K). Six healthy subjects underwent four biopsies of the vastus lateralis, distributed into two distinct visits spaced by 48 hrs. At visit 1, a basal biopsy in the right leg was performed in the morning (R1) followed by a second in the left leg in the afternoon (AF). At visit 2, a second basal biopsy (R2) was collected from the right leg. Low intensity mobilization (3 * 20 right leg extensions) was performed and a final biopsy (Mob) was collected using the same incision site as R2. RESULTS: Akt and p70 S6K phosphorylation levels were increased by 83% when AF biopsy was compared to R1. Mob condition induced important phosphorylation of p70 S6K when compared to R2. Comparison of R1 and R2 biopsies revealed a relative stability of the signal for both total and phosphorylated proteins. CONCLUSIONS: This study highlights the importance to standardize muscle biopsy protocols in order to minimize the method-induced variation when analyzing Western blot signals. PMID- 22075212 TI - Diagnostic epitope variability within Taenia solium 8 kDa antigen family: implications for cysticercosis immunodetection. AB - To study diagnostic epitopes within the Taenia solium 8 kDa antigen family, six overlapping synthetic peptides from an 8 kDa family member (Ts8B2) were synthesized and evaluated by ELISA and MABA with sera from patients with neurocysticercosis (NCC), from infected pigs and from rabbits immunized with recombinant Ts8B2 protein. The pre-immune rabbit sera and the Ts8B2 recombinant protein served as negative and positive controls, respectively. A similar analysis was done with the already described antigenic peptides from another member of the 8 kDa family, highly similar to Ts8B2, the CyDA antigen. Surprisingly, neither the Ts8B2 peptides nor the CyDA peptides were recognized by infected human and porcine sera. However, the entire Ts8B2 recombinant, as well as amino and carboxy-terminal halves were recognized by the positive serum samples. The observed lack of recognition of linear Ts8B2 peptides suggests that the principal serological response to the Ts8B2 family is focused on conformational epitopes in contrast to the previously observed antigenicity of the CyDA peptides. This differential antigenicity of 8 kDa family peptides could be related with parasite antigenic variability. The fact that rabbits experimentally immunized with Ts8B2 did make anti-peptide antibodies to peptides Ts8B2-6 and CyDA-6, located in the carboxy-terminal region demonstrated that the Ts8B2 peptides are not intrinsically non-immunogenic. PMID- 22075213 TI - Immunohistochemical expression of matrix metalloproteinases in the rabbit corneal epithelium upon UVA and UVB irradiation. AB - Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in tissue remodeling and wound healing. These enzymes degrade and also synthesize components of the extracellular matrix. Overexpression of MMPs results in excessive extracellular matrix degradation and tissue destruction. In the cornea, destructive processes may lead to scarring and loss of vision. In this study MMPs (types 1, 2, 7, 8, 9 and 14) were examined immunohistochemically in the normal rabbit corneal epithelium and in epithelium irradiated in vivo with similar doses of UVB or UVA radiation (UVB rays 312 nm, UVA rays 365 nm, daily dose 1.01 J/cm(2) for four days). Results show that MMPs studied revealed low expression in the normal corneal epithelium, whereas after repeated UVB irradiation the expression of MMPs was significantly increased in the corneal epithelium, in ascending order: MMP-2, MMP-9, MMP-1, and MMP-7 with MMP-8. In contrast, compared to normal corneas, repeated UVA radiation did not significantly change the expression of MMPs in the irradiated corneal epithelium. MMP-14 was expressed at very low levels in all studied corneas, whereas no significant changes were detected upon UV exposure. In conclusion, UV radiation of shorter wavelength (UVB) induced an increase in expression of all MMPs except MMP-14. It is suggested that overexpression of MMPs in the corneal epithelium contributes to the damaging effect of UVB radiation to the cornea. PMID- 22075214 TI - Secular trends in adult sleep duration: a systematic review. AB - OBJECTIVES: Little evidence exists to support the common assertion that adult sleep duration has declined. We investigated secular trends in sleep duration over the past 40 years through a systematic review. METHODS: Systematic search of 5 electronic databases was conducted to identify repeat cross-sectional studies of sleep duration in community-dwelling adults using comparable sampling frames and measures over time. We also attempted to access unpublished or semi-published data sources in the form of government reports, theses and conference proceedings. No studies were excluded based on language or publication date. The search identified 278 potential reports, from which twelve relevant studies were identified for review. RESULTS: The 12 studies described data from 15 countries from the 1960s until the 2000s. Self-reported average sleep duration of adults had increased in 7 countries: Bulgaria, Poland, Canada, France, Britain, Korea and the Netherlands (range: 0.1-1.7 min per night each year) and had decreased in 6 countries: Japan, Russia, Finland, Germany, Belgium and Austria (range: 0.1-0.6 min per night each year). Inconsistent results were found for the United States and Sweden. CONCLUSIONS: There has not been a consistent decrease in the self reported sleep duration of adults from the 1960s to 2000s. However, it is unclear whether the proportions of very short and very long sleepers have increased over the same period, which may be of greater relevance for public health. PMID- 22075215 TI - When gender matters: restless legs syndrome. Report of the "RLS and woman" workshop endorsed by the European RLS Study Group. AB - Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism. PMID- 22075216 TI - Understanding couples' attitudes on prenatal HIV testing in the Democratic Republic of Congo. AB - BACKGROUND: The prevalence of HIV-serodiscordant couples is increasing. In these couples, one member is infected with HIV and the other one is not, so HIV testing for both members of the couple remains one of the significant challenges in the prevention of sexual transmission of HIV within the couple. The aim of this study was to analyze couples' attitudes toward HIV testing after prenatal HIV testing offered to pregnant women and analyze the males' behavior with regard to their own HIV testing. METHODS: One hundred and forty-three pregnant women and their partners were interviewed in the Lubumbashi health district in the Democratic Republic of the Congo. The usual descriptive statistics were applied. RESULTS: Seventy-one percent of the couples declared that they accepted the HIV testing proposed to the woman and approximately 64% of the couples said they had discussed the HIV testing proposed in prenatal healthcare clinics. However, this dialogue seemed to have a poor impact on the HIV testing of the male partner: no male partner was tested in spite of the high proportion of men encouraged to do so. Nearly 30% and 50% of the couples disagreed on systematic condom use and the need for the husband's permission to undergo HIV testing, respectively. Twenty nine percent of the couples did not wish to have the male sexual partner present at the prenatal consultation. CONCLUSION: The majority of men considered that their wife's HIV testing gives them information about their own HIV status and this makes HIV testing difficult for both members of the couple. Better management of the couple in HIV screening and prevention programs therefore seems necessary. PMID- 22075217 TI - Impact of video-assisted thoracoscopic surgery on benign resections for solitary pulmonary nodules. AB - BACKGROUND: Differentiating benign from malignant pulmonary lesions is an important part of surgical decision making. We reviewed our experience of resecting suspicious pulmonary nodules to test the hypothesis that the increased use of video-assisted thoracic surgery (VATS) has increased the resection rate of benign lesions. METHODS: A retrospective analysis was carried out on 3,217 patients who underwent resection for focal pulmonary lesions between 1995 and 2009. Resection method, computed tomography (CT) results, positron emission tomography (PET) results, and operative and pathology reports were reviewed. RESULTS: Pulmonary resection was by thoracotomy/median sternotomy in 2,632 of 3,217 (82%) patients and by VATS in 585 of 3,217 (18%). Resections performed by VATS increased from 129 of 2,150 (6%) between 1995 and 2005 to 453 of 1,067 (42.4%) between 2006 and 2009. From 2006 to 2009, 31.4% of lobectomies and 63.9% of wedge resections were performed by VATS. Benign lesions were found in 350 of 3,217 (10.8%) patients. Between 1995 and 2005 our resection rate of benign lesions was 192 of 2,150 (8.9%). From 2006 to 2009, it increased to 158 of 1,067 (14.8%), of which 85 of 456 (20.8%) were VATS and 63 of 611(10.3%) were open procedures. The benign lesion resection rate was 91 of 237 (38.3%) for VATS wedges, 49 of 134 (36.6%) for open wedges, 4 of 219 (1.8%) for VATS lobectomies, and 14 of 477 (2.9%) for open lobectomies. 257 of 456 (52.0%) of the VATS resections were wedges compared with 134 of 611 (21.9%) of the open procedures. CONCLUSIONS: There has been an increase in pulmonary resections performed by VATS. This is associated with an increase in benign lesion resections. The benign lesion resection rate for VATS was twice that of the open procedure rate. However the benign lesion resection rates for wedge resections and lobectomies were not significantly different in regard to approach. VATS has led to an increase in our overall benign lesion resection rate, which can be explained by the increased number of VATS wedge resections that are being performed. PMID- 22075218 TI - Comparison of mechanical properties of human ascending aorta and aortic sinuses. AB - BACKGROUND: Computational finite element models of the aortic root have previously used material properties of the ascending aorta to describe both aortic sinuses and ascending aorta. We have previously demonstrated significant material property differences between ascending aorta and sinuses in pigs. However, it is unknown whether these regional material property differences exist in humans. The main objective of this study was to investigate biomechanics of fresh human ascending aorta and aortic sinuses and compare nonlinear material properties of these regions. METHODS: Fresh human aortic root specimens obtained from the California Transplant Donor Network (Oakland, CA) were subjected to displacement-controlled equibiaxial stretch testing within 24 hours of harvest. Stress-strain data recorded were used to derive strain energy functions for each region. Tissue behavior was quantified by tissue stiffness and a direct comparison was made between different regions of aortic root at physiologic stress levels. RESULTS: All regions demonstrated a nonlinear response to strain during stretch testing in both circumferential and longitudinal directions. No significant difference in tissue stiffness was found between anterior and posterior regions of the ascending aorta or among the three sinuses in both directions. However, our results demonstrated that human ascending aorta is significantly more compliant than aortic sinuses in both circumferential and longitudinal directions within the physiologic stress range. CONCLUSIONS: Significant material and structural differences were observed between human ascending aorta and aortic sinuses. Regionally specific material properties should be employed in computational models used to assess treatments of structural aortic root disease. PMID- 22075219 TI - Selective left subclavian ligation in total aortic arch replacement. AB - BACKGROUND: The left subclavian artery (LSA) is usually difficult to manipulate in total aortic arch replacement procedures if it is displaced by huge false lumens in the ascending aorta or right hemiarch. We summarize our experience of selectively ligating the deeply located LSA in total aortic arch replacement and stented "elephant trunk" implantation procedures for Stanford type A aortic dissection. METHODS: Data of 29 patients with deep LSA undergoing total arch replacement and stented "elephant trunk" implantation from January 2008 to June 2010 were reviewed. The LSA was ligated because of the difficult exposure (21 males, 8 females, age 19 to 55). Collateral circulation of the circle of Willis and bilateral vertebral arteries were assessed thoroughly by preoperative imaging and intraoperative observations. If collateral circulation was sufficient, LSA was ligated; if insufficient, an additional bypass graft was created from the ascending aorta to the left axillary artery. RESULTS: Twenty-eight patients survived the operation with 1 early death. Postoperative blood pressures were lower in the left arm than in the right (78+/-17.3 vs 126+/-3.7 mm Hg, p<0.01), but oxygen saturation, skin temperature, and strength of the left hand were normal. The surviving patients have been followed for 16.6+/-9.0 months (6 to 36) and none had symptoms of LSA steal syndrome or arm ischemia. CONCLUSIONS: Ligation of the LSA after strict evaluation of collateral circulation could be safe for type A dissection patients if the exposure is insufficient, and this method can simplify the operation significantly. PMID- 22075220 TI - Amplitude-integrated electroencephalography and brain injury in infants undergoing Norwood-type operations. AB - BACKGROUND: Perioperative brain injury is common in infants undergoing cardiac surgery. Amplitude-integrated electroencephalography (aEEG) provides real-time neurologic monitoring and can identify seizures and abnormalities of background cerebral activity. We aimed to determine the incidence of perioperative electrical seizures, and to establish the background pattern of aEEG, in neonates undergoing Norwood-type palliations for complex congenital heart disease in relation to outcome at 2 years. METHODS: Thirty-nine full-term neonates undergoing Norwood-type operations underwent aEEG monitoring before and during surgery and for 72 hours postoperatively. The perfusion strategy included full flow moderately hypothermic cardiopulmonary bypass with antegrade cerebral perfusion. Amplitude-integrated electroencephalography tracings were reviewed for seizure activity and background pattern. Survivors underwent neurodevelopmental outcome assessment using the Bayley Scales of Infant Development (3rd edition) at 2 years of age. RESULTS: Thirteen (33%) infants had electrical seizures, including 9 with intraoperative seizures and 7 with postoperative seizures. Seizures were associated with significantly increased mortality, but not with neurodevelopmental impairment in survivors. Delay in recovery of the aEEG background beyond 48 hours was also associated with increased mortality and worse motor development. CONCLUSIONS: Perioperative seizures were common in this cohort. Intraoperative seizures predominantly affected the left hemisphere during antegrade cerebral perfusion. Delayed recovery in aEEG background was associated with increased risk of early mortality and worse motor development. Ongoing monitoring is essential to determine the longer-term significance of these findings. PMID- 22075221 TI - Evaluation of hypophosphatemia: lessons from patients with genetic disorders. AB - Phosphate is a key component of several physiologic pathways, such as skeletal development, bone mineralization, membrane composition, nucleotide structure, maintenance of plasma pH, and cellular signaling. The kidneys have a key role in phosphate homeostasis, with 3 hormones having important roles in renal phosphate handling: parathyroid hormone, fibroblast growth factor 23 (FGF-23), and 1,25 dihydroxyvitamin D. Independent of the genetic diseases affecting the FGF-23 pathway (such as hypophosphatemic rickets), hypophosphatemia is a frequent condition encountered in daily practice, and untreated critical hypophosphatemia can induce hemolysis, rhabdomyolysis, respiratory failure, cardiac dysfunction, and neurologic impairment. Rapid correction thus is necessary to avoid severe complications. The aims of this teaching case are to summarize the causes and biological evaluation of hypophosphatemia and provide an overview of our current understanding of phosphate metabolism. PMID- 22075222 TI - Elevated prepronociceptin, nociceptin/orphanin FQ and nocistatin concentrations in rat chronic constriction nerve injury and diabetic neuropathic pain models. AB - Nociceptin/orphanin FQ (N/OFQ) and nocistatin are derived from the same precursor peptide, prepronociceptin. N/OFQ and nocistatin have been postulated to participate in pain modulation. In this study, we investigated whether the prepronociceptin, N/OFQ and nocistatin concentrations in the brain and spinal cord would be altered in chronic constriction injury and diabetic rat neuropathic pain models. Total brain and spinal cord lysates as well as serum from rats that had undergone chronic constriction injury and streptozocin-induced diabetic neuropathy were used to determine the concentrations of three peptides using competitive radioimmunoassay. We found that N/OFQ and prepronociceptin concentrations were significantly raised in both rat neuropathic pain models. Nocistatin was raised in the brains of post traumatic neuropathy pain rats. Overall, our data have demonstrated for the first time that prepronociceptin, N/OFQ and nocistatin concentrations are significantly altered at different tissues of two rat neuropathy pain models. PMID- 22075223 TI - Unperceivable noise to active light touch effects on fast postural sway. AB - Human postural sway during quiet standing is reduced when a fingertip lightly touches a stable surface. The tactile feedback information from the fingertip has been considered responsible for this effect of light touch. Studies have shown that a noise-like minute stimulation to the sensory system can improve the system's weak signal detection. In the present study, we investigated whether a noise-like unperceivable vibration on the fingertip enhances its tactile sensation and facilitates the effect of light touch during quiet standing. Thirteen volunteers maintained quiet standing while lightly touching a touch surface with the index fingertip. Based on each subject's vibrotactile threshold (VT), a noise-like vibration was applied to the touch surface at amplitudes under (0.5VT) or at VT (1.0VT), in addition to the normal light touch condition (no vibration, 0VT). The results showed that the mean velocities of the foot center of pressure (CoP) in both the anteroposterior (AP) and mediolateral (ML) directions were significantly reduced at 0.5VT compared to 0VT and 1.0VT (P<0.05), while there was no significant difference between 1.0VT and 0VT (P>0.05). Frequency analysis of CoP revealed that the power of high-frequency fluctuation (1-10Hz) was significantly reduced at 0.5VT (P<0.05), whereas no significant change was observed in that of low-frequency sway (below 1Hz) (P>0.05). These results indicate that an unperceivable noise-like vibration can facilitate the effect of light touch on postural stability, by further reducing fast postural sway. PMID- 22075224 TI - In vitro protection of auditory hair cells by salicylate from the gentamicin induced but not neomycin-induced cell loss. AB - Salicylate has been shown to protect animals and people from the gentamicin induced hearing loss. The objective of our study was to determine if salicylate is otoprotective in vitro. In this fashion, we wanted to validate the use of explant culture system for future studies on the ototoxicity prevention. In addition, we wanted to find out if salicylate protects from the ototoxicity of other aminoglycosides. As a model, we used the membranous cochlear tissues containing the organ of Corti, spiral limbus and spiral ganglion neurons dissected from the cochleas of p3-p5 Wistar pups. The explants were divided into apical, medial and basal parts and cultured in presence or absence of 100MUM gentamicin, 100MUM neomycin and 5mM salicylate. Following the tissue fixation and staining with phalloidin-TRITC, the number of inner and outer hair cells (IHCs, OHCs) was scored under the fluorescent microscope. Presence of 5mM salicylate in explants cultures exposed to 100MUM gentamicin significantly reduced the loss of IHCs and OHCs, as compared to explants exposed to gentamicin alone. In contrast, neomycin-induced auditory hair cell loss remained unaffected by the presence of salicylate. Our results corroborate earlier in vivo findings and validate the use of cochlear explants for future studies on ototoxicity and its prevention. Moreover, the inability of salicylate to prevent neomycin-induced ototoxicity implies possible differences between the mechanisms of auditory hair cell loss induced by gentamicin and neomycin. PMID- 22075225 TI - Neuronostatin induces hyperalgesia in formalin test in mice. AB - Neuronostatin, a newly identified peptide encoded by the somatostatin (SST) gene, was proved to produce significant antinociceptive effect in mouse tail immersion test. However, the effect of neuronostatin on tonic pain was still not clear. The aim of this study was to investigate the effect of neuronostatin in the formalin test and its possible mechanism. We found that intracerebroventricular (i.c.v.) administration of neuronostatin (1, 3, 6, 12nmol/mouse) increased licking in a dose-related manner during the late phase, but did not affect the early phase of formalin test in mice. In addition, the hyperalgesic effect during the late phase was completely reversed by melanocortin 3/4 receptor antagonist SHU9119 (50pmol/mouse) or opioid receptor antagonist naloxone (5nmol/mouse), but not GABAA receptor antagonist bicuculline (1086pmol/mouse). These data suggested that the hyperalgesic response induced by neuronostatin was dependent upon the central melanocortin system and endogenous opioid system. In conclusion, these results indicated that neuronostatin may be a new neuropeptide with important role in the modulation of acute and tonic pain. PMID- 22075226 TI - Membrane protein structural bioinformatics. AB - Despite the increasing number of recently solved membrane protein structures, coverage of membrane protein fold space remains relatively sparse. This necessitates the use of computational strategies to investigate membrane protein structure, allowing us to further our understanding of how membrane proteins carry out their diverse range of functions, while aiding the development of novel predictive tools with which to probe uncharacterised folds. Analysis of known structures, the application of machine learning techniques, molecular dynamics simulations and protein structure prediction have enabled significant advances to be made in the field of membrane protein research. In this communication, the key bioinformatic methods that allow the characterisation of membrane proteins are reviewed, the tools available for the structural analysis of membrane proteins are presented and the contribution these tools have made to expanding our understanding of membrane protein structure, function and stability is discussed. PMID- 22075227 TI - Transition to seizure: from "macro"- to "micro"-mysteries. AB - One of the most terrifying aspects of epilepsy is the sudden and apparently unpredictable transition of the brain into the pathological state of an epileptic seizure. The pathophysiology of the transition to seizure still remains mysterious. Herein we review some of the key concepts and relevant literatures dealing with this enigmatic transitioning of brain states. At the "MACRO" level, electroencephalographic (EEG) recordings at time display preictal phenomena followed by pathological high-frequency oscillations at the seizure onset. Numerous seizure prediction algorithms predicated on identifying changes prior to seizure onset have met with little success, underscoring our lack of understanding of the dynamics of transition to seizure, amongst other inherent limitation. We then discuss the concept of synchronized hyperexcited oscillatory networks underlying seizure generation. We consider these networks as weakly coupled oscillators, a concept which forms the basis of some relevant mathematical modeling of seizure transitions. Next, the underlying "MICRO" processes involved in seizure generation are discussed. The depolarization of the GABA(A) chloride reversal potential is a major concept, facilitating epileptogenesis, particularly in immature brain. Also the balance of inhibitory and excitatory local neuronal networks plays an important role in the process of transitioning to seizure. Gap junctional communication, including that which occurs between glia, as well as ephaptic interactions are increasingly recognized as critical for seizure generation. In brief, this review examines the evidence regarding the characterization of the transition to seizure at both the "MACRO" and "MICRO" levels, trying to characterize this mysterious yet critical problem of the brain state transitioning into a seizure. PMID- 22075228 TI - [Cyclic vomiting in association with chronic cannabis abuse]. PMID- 22075229 TI - [Acinetobacter baumannii. An opportunistic pathogen offside?]. PMID- 22075230 TI - [Noninvasive mechanical ventilation in the exacerbation of respiratory diseases]. AB - Noninvasive ventilation (NIV) utilization has experienced an exponential growth in the last 25 years immediately after the introduction of the positive pressure and the nasal mask. Patients with acute, chronic and acute on chronic respiratory failure are candidates to be treated by this therapeutic modality. Its utilization inside the hospital is very heterogeneous being indicated for diverse patients by different levels of complexity and severity levels. We have scientific evidence of the maximum level for certain problems such as COPD exacerbations with respiratory acidosis, acute pulmonary edema, or patients with solid and hematologic transplantation, although its utilization has been generalized to many other clinical scenes using minor levels of evidence. NIV is also used successfully in patients of advanced age, patients with do not intubate orders or even patients with severe comorbidities. Finally, NIV could be used as a palliative tool. The continuous technological evolution and the need of formation of the professionals demands organizational changes in the hospitals and the necessity to define specific areas for most severe patients, such as respiratory intermediate care units. PMID- 22075231 TI - [Biomarkers and suspicion of infection in emergency departments]. PMID- 22075232 TI - Pregnancy outcomes following use of escitalopram: a prospective comparative cohort study. AB - Escitalopram is a serotonin reuptake inhibitor prescribed for depression and anxiety. There is a paucity of information regarding safety in pregnancy. The objective of this study was to determine whether escitalopram is associated with an increased risk for major malformations or other adverse outcomes following use in pregnancy. The authors analyzed pregnancy outcomes in women exposed to escitalopram (n = 212) versus other antidepressants (n = 212) versus nonteratogenic exposures (n = 212) and compared the outcomes. Among the escitalopram exposures were 172 (81%) live births, 32 (15%) spontaneous abortions, 6 (2.8%) therapeutic abortions, 3 stillbirths (1.7%), and 3 major malformations (1.7%). The only significant differences among groups was the rate of low birth weight (<2500 g) and overall mean birth weight (P = .225). However, spontaneous abortion rates were higher in both antidepressant groups (15% and 16%) compared with controls (8.5%; P = .066). There were lower rates of live births (P = .006), lower overall birth weight (P < .001), and increased rates of low birth weight (<2500 g; P = .009) with escitalopram. Spontaneous abortion rates were nearly double in both antidepressant groups (15% and 16%) compared with controls (8.5%) but not significant (P = .066). Escitalopram does not appear to be associated with an increased risk for major malformations but appears to increase the risk for low birth weight, which was correlated with the increase in infants weighing <2500 g. In addition, the higher rates of spontaneous abortions in both antidepressant groups confirmed previous findings. PMID- 22075233 TI - New cholesterol esterase inhibitors based on rhodanine and thiazolidinedione scaffolds. AB - We present a new class of inhibitors of pancreatic cholesterol esterase (CEase) based on 'priviledged' 5-benzylidenerhodanine and 5-benzylidene-2,4 thiazolidinedione structural scaffolds. The lead structures (5 benzylidenerhodanine 4a and 5-benzylidene-2,4-thiazolidinedione 4b) were identified in an in-house screening and these inhibited CEase with some selectivity over another serine hydrolase, acetylcholinesterase (AChE) (4a, CEase IC(50)=1.76 MUM vs AChE IC(50)=5.14 MUM and 4b, CEase IC(50)=5.89 MUM vs AChE IC(50) >100 MUM). A small library of analogs (5a-10a) containing a core amino acid in place of the glycerol group of the lead structures, was prepared to explore other potential binding interaction with CEase. These analogs inhibited CEase with IC(50) values ranging from 1.44 to 85 MUM, with the majority exhibiting some selectivity for CEase versus AChE. The most potent compound of the library (10a) had 17-fold selectivity over AChE. We also report molecular docking (with CEase) and detailed kinetic analysis on the amino acid analogs to further understand the associated structure-activity relationships. PMID- 22075234 TI - Synthesis and binding assays of novel 3,3-dimethylpiperidine derivatives with various lipophilicities as sigma1 receptor ligands. AB - Starting from two carbocyclic analogs, a series of 3,3-dimethylpiperidine derivatives was prepared and tested in radioligand binding assays at sigma(1) and sigma(2) receptors, and at Delta(8)-Delta(7) sterol isomerase (SI) site. The novel compounds mostly bear heterocyclic rings or bicyclic nucleus of differing lipophilicities. Compounds 18a and 19a,b demonstrated the highest sigma(1) affinity (K(i)=0.14-0.38 nM) with a good selectivity versus sigma(2) binding. Among them, 18a had the lowest ClogD value (3.01) and only 19b was selective versus SI too. Generally, it was observed that more planar and hydrophilic heteronuclei conferred a decrease in affinity for both sigma receptor subtypes. PMID- 22075235 TI - Molecular drug-organiser: synthesis, characterization and biological evaluation of penicillin V and/or nalidixic acid calixarene-based podands. AB - Two well-known antibiotic heterocycles, the 'quinolone' nalidixic acid and the beta-lactam penicillin V, active at different levels of the bacterial growth process, have been attached via an ether-ester junction to the p-tert butylcalix[4]arene lower rim, in alternate position. The resulting hydrophobic molecular drug-organisers were fully characterized, and evaluated over two Gram negative and three Gram positive reference strains, using disk diffusion assays with disks impregnated with solution of title compound in pure DMSO. An interesting activity was observed over Staphylococcus aureus ATCC 25923 with the dis-symmetrical podand incorporating one penicillin and one nalidixic ester moieties. PMID- 22075237 TI - Cerebellar dysfunction may play an important role in vascular dementia. AB - The cerebellum has traditionally been seen as a brain area limited to the coordination of voluntary movement, gait, posture, speech, and motor functions. There are increasing evidence, however, proving that the cerebellum is implicated in processes associated with the control of cognition, behavior, and psychiatric illness. Furthermore, the fact that the cerebellum is reciprocally connected to a broad range of limbic structures including the amygdale and hippocampus, as well as the cerebral cortex including the prefrontal areas, provides a strong neuroanatomical argument in favor of cerebellar involvement in cognition regulation. Studies have already found the fact that after stroke, the cerebellum suffered from reduction in metabolism and blood flow in the cerebellar hemisphere contralateral to a destructive cerebral lesion. The notion of crossed cerebellar diaschisis (CCD) may contribute to the explanation of the phenomenon. Consequently, theoretically, stroke in any part of the brain including frontal lobe and hippocampus, will affect cerebellar function and the later then results in vascular dementia (VD). More recently, a few clinical trials found that electrical stimulation of fastigial nucleus (FNS) in cerebellum could improve symptom of VD, though the relationship between cerebellum and VD is unclear. Taken together, there seems to be sufficient empirical ground to assume that the cerebellum plays a role in the regulation of VD. The hypotheses of cerebellar role in VD, which will be discussed in this paper, if confirmed, may lead to the formulation of new pathogenesis and new therapeutic approaches to VD. PMID- 22075236 TI - A novel regimen of alternate day clopidogrel would provide a cost-effective strategy to prevent very late stent thrombosis. AB - BACKGROUND/OBJECTIVES: ACC/AHA/SCAI recommendations include dual anti-platelet therapy (aspirin and clopidogrel) for 12 months after drug-eluting stent percutaneous coronary intervention (DES PCI). Numerous case reports have emerged of "very late stent thrombosis" (VLST) (>1 year post-DES-PCI) even 1-5 years after DES-PCI manifesting with myocardial infarction and death when clopidogrel therapy was interrupted or stopped. HYPOTHESIS: We hypothesize that a novel regimen of alternate day clopidogrel would provide a cost-effective strategy to prevent VLST taking into account the known facts about clopidogrel pharmacodynamics, stent endothelialization and stent thrombosis. We hypothesized that the degree of anti-platelet effect required to prevent VLST decreases with time as the stent endothelializes-that is the "therapeutic threshold" required to prevent VLST decreases with time. The anti-platelet effect of clopidogrel lasts for 5-7 days. Typically, stent thrombosis on interruption of clopidogrel (with bare metal stents within first 30 days) occurs after 3-4 days signifying recovery of enough platelet function to produce stent thrombosis--recovery of platelet inhibition beyond the therapeutic threshold. Since the therapeutic threshold required to prevent VLST in DES after 1 year is much lower, this degree of platelet inhibition can be conceivably achieved with just administering clopidogrel on alternate days. EMPIRICAL DATA: We studied efficacy and safety of regimen of daily aspirin 81 mg and alternate-day clopidogrel 75 mg beyond 12 months after PCI with DES for prevention of VLST by following 347 patients for occurrence of death, myocardial infarction (MI), VLST, target vessel revascularization (TVR) and bleeding. There were no occurrence of major bleeding, VLST events or death. CONCLUSIONS: Long term dual anti-platelet therapy with aspirin 81 mg daily and clopidogrel 75 mg every other day beyond 12 months after PCI with DES may be a safe and efficacious cost-saving strategy to prevent VLST. PMID- 22075238 TI - Local Jekyll and global Hyde: the dual identity of face identification. AB - The main concern in face-processing research is to understand the processes underlying the identification of faces. In the study reported here, we addressed this issue by examining whether local or global information supports face identification. We developed a new methodology called "iHybrid." This technique combines two famous identities in a gaze-contingent paradigm, which simultaneously provides local, foveated information from one face and global, complementary information from a second face. Behavioral face-identification performance and eye-tracking data showed that the visual system identified faces on the basis of either local or global information depending on the location of the observer's first fixation. In some cases, a given observer even identified the same face using local information on one trial and global information on another trial. A validation in natural viewing conditions confirmed our findings. These results clearly demonstrate that face identification is not rooted in a single, or even preferred, information-gathering strategy. PMID- 22075239 TI - It's not all about me: motivating hand hygiene among health care professionals by focusing on patients. AB - Diseases often spread in hospitals because health care professionals fail to wash their hands. Research suggests that to increase health and safety behaviors, it is important to highlight the personal consequences for the actor. However, because people (and health care professionals in particular) tend to be overconfident about personal immunity, the most effective messages about hand hygiene may be those that highlight its consequences for other people. In two field experiments in a hospital, we compared the effectiveness of signs about hand hygiene that emphasized personal safety ("Hand hygiene prevents you from catching diseases") or patient safety ("Hand hygiene prevents patients from catching diseases"). We assessed hand hygiene by measuring the amount of soap and hand-sanitizing gel used from dispensers (Experiment 1) and conducting covert, independent observations of health care professionals' hand-hygiene behaviors (Experiment 2). Results showed that changing a single word in messages motivated meaningful changes in behavior: The hand hygiene of health care professionals increased significantly when they were reminded of the implications for patients but not when they were reminded of the implications for themselves. PMID- 22075240 TI - Editorial. Polish blood transfusion service. PMID- 22075241 TI - Endometrial cancer survivors' assessment of the benefits of exercise. AB - OBJECTIVE: The majority of women who have had endometrial cancer remain at risk for obesity related diseases. The social cognitive theory was used to explore their beliefs about exercise to aid in the development of effective interventions. METHODS: Women who had been treated for Stage I endometrial cancer were asked about their level of exercise to determine if they had been exercising regularly for more than 6 months (exercisers vs non-exercisers). They were asked to rate the likelihood that exercise would result in various health outcomes (expectations) and to rate the importance of these outcomes (expectancies). Scores for how likely exercise would result in an outcome of importance were calculated. Height and weight were obtained from nurses for calculation of BMI. Statistics were conducted using SPSS v 15. RESULTS: There were 106 valid questionnaires (86% participation rate); 41% were exercisers. Mean BMI was significantly lower in exercisers (31.6 +/- 1.2 vs. 37.3 +/- 1.2, p=0.001); a significantly greater proportion reported not having diabetes, heart disease or hypertension (69.8% vs. 49.2%, p=0.035). Exercisers were significantly more likely to report that feeling better physically and emotionally versus reducing the risk of diseases were likely and important outcomes of exercise (18.2 +/- 0.8 vs 15.0 +/- 1.0, p=0.002). CONCLUSIONS: Exercisers identified outcomes of exercise that are more immediate and subjective as being important and likely outcomes of exercise. Focusing on these aspects of exercise (feeling better physically and emotionally) may aid in the development of effective interventions for non-exercisers. PMID- 22075243 TI - Utility of capsule endoscopy for evaluating anthelmintic efficacy in fully conscious dogs. AB - The current accepted standard for evaluating the efficacy of gastrointestinal anthelmintic drugs is necropsy of infected animals followed by a comparison of worm counts between treated and non-treated groups. In this study capsule endoscopy, a minimally invasive method of imaging the small intestine of humans, is evaluated as a possible alternative to necropsy for the purposes of worm quantification in dogs. Eighteen Beagle dogs were included in this study. These dogs were part of a separate trial intended to determine the efficacy of various candidate parasiticides against Ancylostoma caninum via the necropsy standard. Dogs were inoculated with A. caninum L3s 4 weeks prior to treatment with one of the candidate compounds; a control group (n=8) received no treatment. Capsule endoscopy was performed 6-14 days post-treatment, followed by necropsy the following day. Seventeen dogs had complete examinations, i.e. the capsule traversed the small intestine and reached the colon within the battery life of the capsule. A strong correlation (r(s)=0.87, P<0.0001) was observed between the worm counts acquired by capsule endoscopy and necropsy. There was no clear relationship between the ability of the capsule endoscope to detect hookworms and either visibility of the intestinal lumen or small intestinal transit time. Generation of a virtual spatial record of hookworm location from the capsule endoscopy data revealed a temporal trend, with the majority of worms present in the proximal small intestine in the morning versus the central to distal small intestine in the afternoon. Worm distribution as determined by capsule endoscopy closely resembled post-mortem findings. In conclusion, capsule endoscopy shows promise as an alternative to necropsy for the enumeration of A. caninum in the canine small intestine, although further work is required to improve completion rates and optimise intestinal examination. PMID- 22075242 TI - Molecular cloning and preliminary function study of iron responsive element binding protein 1 gene from cypermethrin-resistant Culex pipiens pallens. AB - BACKGROUND: Insecticide resistance jeopardizes the control of mosquito populations and mosquito-borne disease control, which creates a major public health concern. Two-dimensional electrophoresis identified one protein segment with high sequence homology to part of Aedes aegypti iron-responsive element binding protein (IRE-BP). METHOD: RT-PCR and RACE (rapid amplification of cDNA end) were used to clone a cDNA encoding full length IRE-BP 1. Real-time quantitative RT-PCR was used to evaluate the transcriptional level changes in the Cr-IRE strain Aedes aegypti compared to the susceptible strain of Cx. pipiens pallens. The expression profile of the gene was established in the mosquito life cycle. Methyl tritiated thymidine (3H-TdR) was used to observe the cypermethrin resistance changes in C6/36 cells containing the stably transfected IRE-BP 1 gene of Cx. pipiens pallens. RESULTS: The complete sequence of iron responsive element binding protein 1 (IRE-BP 1) has been cloned from the cypermethrin-resistant strain of Culex pipiens pallens (Cr-IRE strain). Quantitative RT-PCR analysis indicated that the IRE-BP 1 transcription level was 6.7 times higher in the Cr IRE strain than in the susceptible strain of 4th instar larvae. The IRE-BP 1 expression was also found to be consistently higher throughout the life cycle of the Cr-IRE strain. A protein of predicted size 109.4 kDa has been detected by Western blotting in IRE-BP 1-transfected mosquito C6/36 cells. These IRE-BP 1 transfected cells also showed enhanced cypermethrin resistance compared to null transfected or plasmid vector-transfected cells as determined by 3H-TdR incorporation. CONCLUSION: IRE-BP 1 is expressed at higher levels in the Cr-IRE strain, and may confer some insecticide resistance in Cx. pipiens pallens. PMID- 22075244 TI - Effect of ionizing radiation induced damage of endothelial progenitor cells in vascular regeneration. AB - OBJECTIVE: A number of studies have revealed that stress signaling and subsequent stress responses in stem/progenitor cells are responsible for attenuated regeneration or degenerative disease. Because ionizing radiation (IR), which sensitizes diverse types of stem cells, reportedly induces cardio-circulatory diseases, we hypothesized that IR-induced vascular abnormalities are associated with defects in endothelial progenitor cells (EPCs) that are responsible for vascular homeostasis. METHODS AND RESULTS: We used an irradiated mouse model to mimic the IR effect on vasculogenesis. Mouse EPCs isolated from irradiated mice and human EPCs exposed to IR were used for functional analysis and gene expression study. Under IR exposure, EPCs were depleted, and their function for vasculogenesis in vitro and in vivo was significantly reduced. In such IR mediated stress responses, upregulating p21Cip1 and downregulating vascular endothelial growth factor (VEGF) were mediated by p53 transcriptional activity. CONCLUSIONS: The results of the present study suggest that suppression of p53 would be clinically applicable to (1) minimize the functional defects in EPCs in order to prevent the onset of vascular diseases caused by radiation therapy or radiation exposure and also to (2) provide novel insight into the mechanisms of IR-induced vascular damage and a possible strategy to minimize vascular damage by IR. PMID- 22075245 TI - Urokinase receptor associates with myocardin to control vascular smooth muscle cells phenotype in vascular disease. AB - OBJECTIVE: The urokinase-type plasminogen activator (uPA) and its specific receptor (uPAR) are a potent multifunctional system involved in vascular remodeling. The goal of the study was to unravel the mechanisms of uPA/uPAR directed vascular smooth muscle cell (VSMC) differentiation. METHODS AND RESULTS: Using cultured human primary VSMCs, we identified a new molecular mechanism controlling phenotypic modulation in vitro and in vivo. We found that the urokinase-type plasminogen activator receptor (uPAR) acts together with the transcriptional coactivator myocardin to regulate the VSMC phenotype. uPAR, a glycosylphosphatidylinositol-anchored cell-surface receptor family member, undergoes ligand-induced internalization and nuclear transport in VSMCs. Platelet derived growth factor receptor beta and SUMOylated RanGAP1 mediate this trafficking. Nuclear uPAR associates with myocardin, which is then recruited from the promoters of serum response factor target genes and undergoes proteasomal degradation. This chain of events initiates the synthetic VSMC phenotype. Using mouse carotid artery ligation model, we show that this mechanism contributes to adverse vascular remodeling after injury in vivo. We then cultured cells on a microstructured biomaterial and found that substrate topography induced uPAR mediated VSMC differentiation. CONCLUSIONS: These findings reveal the transcriptional activity of uPAR, controlling the differentiation of VSMCs in a vascular disease model. They also suggest a new role for uPAR as a therapeutic target and as a marker for VSMC phenotyping on prosthetic biomaterials. PMID- 22075246 TI - Dynamic synchrotron imaging of diabetic rat coronary microcirculation in vivo. AB - OBJECTIVE: In diabetes, long-term micro- and macrovascular damage often underlies the functional decline in the cardiovascular system. However, it remains unclear whether early-stage diabetes is associated with in vivo functional impairment in the coronary microvasculature. Synchrotron imaging allows us to detect and quantify regional differences in resistance microvessel caliber in vivo, even under conditions of high heart rate. METHODS AND RESULTS: Synchrotron cine angiograms of the coronary vasculature were recorded using anesthetized Sprague Dawley rats 3 weeks after treatment with vehicle or streptozotocin (diabetic). In the early diabetic state, in the presence of nitric oxide and prostacyclin, vessel diameters were smaller (P<0.01) and endothelium-dependent vessel recruitment was already depressed (P<0.05). Endothelium-dependent and independent vasodilatory responses in individual coronary vessels were not different in vivo. Inhibition of NO and PGI(2) production in diabetes uncovered early localized impairment in dilation. Diabetic animals displayed focal stenoses and segmental constrictions during nitric oxide synthase/cyclooxygenase blockade, which persisted during acetylcholine infusion (P<0.05), and a strong trend toward loss of visible microvessels. CONCLUSIONS: Synchrotron imaging provides a novel method to investigate coronary microvascular function in vivo at all levels of the arterial tree. Furthermore, we have shown that early-stage diabetes is associated with localized coronary microvascular endothelial dysfunction. PMID- 22075247 TI - Objectively assessed physical activity, sedentary time, and coronary artery calcification in healthy older adults. AB - OBJECTIVE: Physical activity is related to lower risk of cardiovascular disease, but data relating to coronary lesions have been conflicting. These inconsistencies may in part be due to unreliable assessment of physical activity and limitations imposed by self-reported data. The purpose of this study was to determine the relationship between objectively measured physical activity and coronary artery calcium (CAC). METHODS AND RESULTS: Participants were 443 healthy men and women (mean age=66+/-6 years), without history or objective signs of coronary heart disease, drawn from the Whitehall II epidemiological cohort. Physical activity was objectively measured using accelerometers worn during waking hours for 7 consecutive days (average daily wear time=889+/-68 minutes/day). CAC was measured in each participant using electron beam computed tomography and was quantified according to the Agatston scoring system. On average, 54.4% of the sample recorded at least 30 minutes/day of moderate to vigorous physical activity (MVPA). There was no association between MVPA and presence of detectable CAC. For the participants with detectable CAC (n=283) a weak inverse relationship between MVPA (minutes/day) and log Agatston score was observed (B=-0.008, 95% CI: -0.16 to 0.00, P=0.05), although the association was no longer present after adjustments for age, sex, and conventional risk factors. No associations were seen for light activity or sedentary time. CONCLUSIONS: Our results confirm no association between objectively assessed physical activity and CAC. Because CAC measures cannot identify more vulnerable lesions, additional studies are required to examine whether physical activity can promote plaque stability. PMID- 22075248 TI - Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. AB - OBJECTIVE: Transsignaling of interleukin (IL)-6 is a central pathway in the pathogenesis of disorders associated with chronic inflammation, such as Crohn disease, rheumatoid arthritis, and inflammatory colon cancer. Notably, IL-6 also represents an independent risk factor for coronary artery disease (CAD) in humans and is crucially involved in vascular inflammatory processes. METHODS AND RESULTS: In the present study, we showed that treatment with a fusion protein of the natural IL-6 transsignaling inhibitor soluble glycoprotein 130 (sgp130) and IgG1-Fc (sgp130Fc) dramatically reduced atherosclerosis in hypercholesterolemic Ldlr(-/-) mice without affecting weight gain and serum lipid levels. Moreover, sgp130Fc treatment even led to a significant regression of advanced atherosclerosis. Mechanistically, endothelial activation and intimal smooth muscle cell infiltration were decreased in sgp130Fc-treated mice, resulting in a marked reduction of monocyte recruitment and subsequent atherosclerotic plaque progression. Of note, patients with CAD exhibited significantly lower plasma levels of endogenous sgp130, suggesting that a compromised counterbalancing of IL 6 transsignaling may contribute to atherogenesis in humans. CONCLUSIONS: These data clarify, for the first time, the critical involvement of, in particular, the transsignaling of IL-6 in CAD and warrant further investigation of sgp130Fc as a novel therapeutic for the treatment of CAD and related diseases. PMID- 22075249 TI - Clinical and genetic association of serum ceruloplasmin with cardiovascular risk. AB - OBJECTIVE: Ceruloplasmin (Cp) is an acute-phase reactant that is increased in inflammatory diseases and in acute coronary syndromes. Cp has recently been shown to possess nitric oxide (NO) oxidase catalytic activity, but its impact on long term cardiovascular outcomes in stable cardiac patients has not been explored. METHODS AND RESULTS: We examined serum Cp levels and their relationship with incident major adverse cardiovascular events (MACE; death, myocardial infarction [MI], stroke) over 3-year follow-up in 4177 patients undergoing elective coronary angiography. We also carried out a genome-wide association study to identify the genetic determinants of serum Cp levels and evaluate their relationship to prevalent and incident cardiovascular risk. In our cohort (age 63+/-11 years, 66% male, 32% history of MI, 31% diabetes mellitus), mean Cp level was 24+/-6 mg/dL. Serum Cp level was associated with greater risk of MI at 3 years (hazard ratio [quartile 4 versus 1] 2.35, 95% confidence interval [CI] 1.79-3.09, P<0.001). After adjustment for traditional risk factors, high-sensitivity C-reactive protein, and creatinine clearance, Cp remained independently predictive of MACE (hazard ratio 1.55, 95% CI 1.10-2.17, P=0.012). A 2-stage genome-wide association study identified a locus on chromosome 3 over the CP gene that was significantly associated with Cp levels (lead single-nucleotide polymorphism rs13072552; P=1.90*10(-11)). However, this variant, which leads to modestly increased serum Cp levels (~1.5-2 mg/dL per minor allele copy), was not associated with coronary artery disease or future risk of MACE. CONCLUSIONS: In stable cardiac patients, serum Cp provides independent risk prediction of long-term adverse cardiac events. Genetic variants at the CP locus that modestly affect serum Cp levels are not associated with prevalent or incident risk of coronary artery disease in this study population. PMID- 22075250 TI - Rap1-Rac1 circuits potentiate platelet activation. AB - OBJECTIVE: The goal of this study was to investigate the potential crosstalk between Rap1 and Rac1, 2 small GTPases central to platelet activation, particularly downstream of the collagen receptor GPVI. METHODS AND RESULTS: We compared the activation response of platelets with impaired Rap signaling (double knock-out; deficient in both the guanine nucleotide exchange factor, CalDAG-GEFI, and the Gi-coupled receptor for ADP, P2Y12), to that of wild-type platelets treated with a small-molecule Rac inhibitor, EHT 1864 (wild-type /EHT). We found that Rac1 is sequentially activated downstream of Rap1 on stimulation via GPVI. In return, Rac1 provides important feedback for both CalDAG-GEFI- and P2Y12 dependent activation of Rap1. When analyzing platelet responses controlled by Rac1, we observed (1) impaired lamellipodia formation, clot retraction, and granule release in both double knock-out and EHT 1864-treated wild-type platelets; and (2) reduced calcium store release in EHT 1864-treated wild-type but not double knock-out platelets. Consistent with the latter finding, we identified 2 pools of Rac1, one activated immediately downstream of GPVI and 1 activated downstream of Rap1. CONCLUSIONS: We demonstrate important crosstalk between Rap1 and Rac1 downstream of GPVI. Whereas Rap1 signaling directly controls sustained Rac1 activation, Rac1 affects CalDAG-GEFI- and P2Y12-dependent Rap1 activation via its role in calcium mobilization and granule/ADP release, respectively. PMID- 22075251 TI - Relationships between recent intraplaque hemorrhage and stroke risk factors in patients with carotid stenosis: the HIRISC study. AB - OBJECTIVE: Intraplaque hemorrhage (IPH) is an emerging marker of plaque instability. However, little is known about the relationships between IPH and traditional risk factors and whether these relationships differ between symptomatic and asymptomatic disease. METHODS AND RESULTS: Two hundred thirty four patients with symptomatic (n=114) or asymptomatic (n=120) carotid stenosis underwent high-resolution plaque magnetic resonance imaging. Seventy-five patients had recent IPH (symptomatic, 33%; asymptomatic, 31%). In symptomatic stenosis, recent IPH was independently associated with degree of stenosis (odds ratio [OR]=4.21, 1.61-10.98 for North American Symptomatic Carotid Endarterectomy Trial >35%; OR=2.92, 1.18-7.24 for European Carotid Surgery Trial >60%), qualifying event (OR=4.13; 1.11-15.32 for stroke or hemispheric transient ischemic attack >=1 hour versus transient ischemic attack <1 hour or ocular symptoms), time from ischemic event (OR=6.65, 1.56-28.35 for <=2 weeks; OR=2.24, 0.87-5.81 for 2-12 weeks versus >12 weeks; P for trend=0.03). In asymptomatic stenosis, IPH was only associated with stenosis severity >70% by ECST (OR=6.65; 1.95-22.73) but not by the NASCET method. CONCLUSIONS: Our findings support the potential link between recent IPH and risk of ipsilateral stroke in symptomatic disease but also imply that prognostic studies should adjust for known stroke risk factors in multivariate analyses. In asymptomatic stenosis, the potential predictive value of recent IPH is less likely to be confounded by stroke risk factors. PMID- 22075252 TI - Inhibitor of differentiation-3 mediates high fat diet-induced visceral fat expansion. AB - OBJECTIVE: Inhibitor of differentiation-3 (Id3) has been implicated in promoting angiogenesis, a key determinant of high-fat diet (HFD)-induced visceral adiposity. Yet the role of Id3 in HFD-induced angiogenesis and visceral adipose expansion is unknown. METHODS AND RESULTS: Id3(-/-) mice demonstrated a significant attenuation of HFD-induced visceral fat depot expansion compared to wild type littermate controls. Importantly, unlike other Id proteins, loss of Id3 did not affect adipose depot size in young mice fed chow diet or differentiation of adipocytes in vitro or in vivo. Contrast enhanced ultrasound revealed a significant attenuation of visceral fat microvascular blood volume in HFD-fed mice null for Id3 compared to wild type controls. HFD induced Id3 and VEGFA expression in the visceral stromal vascular fraction and Id3(-/-) mice had significantly lower levels of VEGFA protein in visceral adipose tissue compared to wild type. Furthermore, HFD-induced VEGFA expression in visceral adipose tissue was completely abolished by loss of Id3. Consistent with this effect, Id3 abolished E12-mediated repression of VEGFA promoter activity. CONCLUSIONS: Results identify Id3 as an important regulator of HFD-induced visceral adipose VEGFA expression, microvascular blood volume, and depot expansion. Inhibition of Id3 may have potential as a therapeutic strategy to limit visceral adiposity. PMID- 22075253 TI - Competing risk of atherosclerotic risk factors for arterial and venous thrombosis in a general population: the Tromso study. AB - OBJECTIVE: To investigate and compare the impact of traditional atherosclerotic risk factors for the risk of arterial and venous thrombosis, taking into account competing risks. METHODS AND RESULTS: In 1994-1995, 26,185 subjects were screened in the Tromso study. Information on traditional atherosclerotic risk factors was obtained by physical examination, blood samples, and questionnaires. Subjects were followed to the first incident event of myocardial infarction (MI) or venous thromboembolism (VTE), or December 31, 2005. During a median of 10.8 years of follow-up, there were 1279 cases of incident MI and 341 VTE events. Advancing age and high body mass index were both associated with MI and VTE. Hazard ratio per decade of age was 2.34 (95% CI: 2.25-2.43) for MI and 1.87 (1.74-2.01) for VTE, and 3 kg/m(2) increase in body mass index was associated with 1.16 (1.11-1.21) and 1.20 (1.12-1.29) increased risk of MI and VTE, respectively. Blood pressure, high levels of triglycerides and total cholesterol, low HDL cholesterol, self reported diabetes, and smoking were all associated with increased risk of MI but not associated with VTE. CONCLUSIONS: Our findings imply that traditional atherosclerotic risk factors, such as smoking, hypertension, dyslipidemia, and diabetes mellitus are not shared by arterial and venous thrombosis. PMID- 22075254 TI - Sodium channel Nav1.6 is up-regulated in the dorsal root ganglia in a mouse model of type 2 diabetes. AB - Neuropathic pain is one of the most common chronic complications of diabetes, of which the underlying mechanisms are unclear. Expression changes of voltage-gated sodium channels in dorsal root ganglia (DRG) are involved in the production of ectopic spontaneous activity. In the present study, we examined the changes of DRG Nav1.6 expression in a mouse model of type 2 diabetes (db/db mice). Db/db mice developed significant and persistent mechanical allodynia from postnatal 2 months compared to the heterozygous littermates (db/+) and C57 mice. Immunofluorescent staining showed that Nav1.6 was highly expressed in the normal DRG (approximately 31.3+/-5.2% of total DRG neurons), especially in the large diameter neurons. In postnatal 5 months in db/db mice, percentage of Nav1.6 positive cells (62.9+/-5.5%) was significantly higher than that in C57 and db/+ mice. Western blot showed that from 2 to 5 months, Nav1.6 was increased by 1.67+/ 0.16, 2.12+/-0.23, 1.89+/-0.32, and 2.01+/-0.35 folds of C57 mice, which were significantly higher than that of the C57 and db/+ mice. Real-time PCR showed that in postnatal 1 month of db/db mice, mRNA level of Nav1.6 was increased by 1.72+/-0.22 fold, which was significantly higher than that of C57 and db/+ mice. Nav1.6 mRNA was increased thereafter and maintained at high levels throughout the observed period. Our results provide direct evidence that type 2 diabetes induces significant and persistent increase of Nav1.6 expression in the DRG, which may participate in the diabetic neuropathic pain. PMID- 22075255 TI - Sphingomonas paucimobilis bacteremia related to intravenous human immunoglobulin injections. PMID- 22075257 TI - Quality of life is reduced in obese dogs but improves after successful weight loss. AB - Obesity is thought to affect quality of life, but limited objective data exist to support this supposition. The current study aim was to use a questionnaire to determine health-related quality of life (HRQOL) both before and after weight loss, in obese client-owned dogs. Fifty obese dogs were included, and represented a variety of breeds and genders. Prior to weight loss, owners were asked to complete a validated standardised questionnaire to determine HRQOL. Thirty of the dogs successfully completed their weight loss programme and reached target, and owners then completed a follow-up questionnaire. The completed questionnaire responses were transformed to scores corresponding to each of four factors (vitality, emotional disturbance, anxiety and pain), and scored on a scale of 0 6. Changes in the scores were used to explore the sensitivity of the questionnaire, and scores were correlated with responses to direct questions about quality of life and pain, as well as weight loss. Dogs that failed to complete their weight loss programme had lower vitality and higher emotional disturbance scores than those successfully losing weight (P=0.03 for both). In the 30 dogs that completed, weight loss led to an increased vitality score (P<0.001), and decreased scores for both emotional disturbance (P<0.001) and pain (P<0.001). However, there was no change in anxiety (P=0.09). The change in vitality score was positively associated with percentage weight loss (r(P)=0.43, P=0.02) and percentage body fat loss (r(P)=0.39, P=0.03). These results indicate demonstrable improvement in HRQOL for obese dogs that successfully lose weight. PMID- 22075256 TI - Haemostatic abnormalities in cats with naturally occurring liver diseases. AB - Alterations in the haemostatic system were characterized in cats with different naturally occurring liver diseases. The study looked at 44 healthy cats and 45 cats with different liver diseases confirmed histologically or cytologically (neoplasia, n=9; inflammation, n=12; hepatic lipidosis, n=13; other degenerative liver diseases, n=11). The following parameters were evaluated: platelet count; prothrombin time; activated partial thromboplastin time; thrombin time; factor (F) II, FV, FVII, FX, and FXIII activities; fibrinogen concentration; activities of antithrombin, protein C, plasminogen, and alpha(2)-plasmin inhibitor, and D dimer concentration. In cats with liver diseases, 44/45 (98%) had one or more abnormalities of the coagulation parameters measured. In cats with inflammatory liver diseases, increased D-dimer concentrations and decreased FXIII activity were the most consistent abnormalities and were found in 83% and 75% of cats, respectively. The most common abnormality in cats with neoplastic liver disease was FXIII deficiency (78%). The most consistent abnormalities in cats with hepatic lipidosis were increased FV activity and D-dimer concentration with 54% of cats having values above the reference range for both parameters. Cats with miscellaneous degenerative liver disease most frequently showed FXIII deficiency (64%). The results of this study show that alterations of single haemostatic components are a frequent finding in cats with liver disease. Activation of haemostasis with subsequent consumptive coagulopathy (rather than decreased synthesis) seems to be responsible for these alterations. Increased blood levels of different haemostatic components in cats with inflammatory lesions may be related to an acute phase reaction. PMID- 22075258 TI - Effects of handle orientation and between-handle distance on bi-manual isometric push strength. AB - Hand-handle interface is seldom considered in contemporary upper limb biomechanical analyses of pushing and pulling strength. A laboratory study was designed to examine if handle rotation in the frontal plane (0 degrees horizontal, 45 degrees , and 90 degrees -vertical), anterior tilt (0 degrees parallel to the frontal plane, and 15 degrees ), and distance between two handles (31 and 48.6 cm) affect pushing strength and subjective rating of handle preference. A special testing station was constructed to elicit upper limb push exertions that involved minimal contribution of the torso and legs. Within the station, four load cells were used to measure the horizontal (forward pushing) and vertical components of the pushing forces. Thirty-one participants performed seated bi-manual pushing strength tests. Comparing to the reference handle configuration (horizontal, straight, and a 31-cm between-handle distance), the 45 degrees -rotated and tilted handles with a 31-cm between-handle distance allowed 6.7% more pushing output, while the horizontal and tilted handles with a 31-cm between-handle distance resulted in 2.8% less. Subjective preference was correlated with normalized pushing strength (r=0.89). Tilted handles, at 45 degrees -rotated and vertical positions received highest subjective ratings of preference among all handle configurations. Men exerted greater pushing strength with the 48.6-cm handle distance while women's capacity was greatest with the 31 cm distance. The results demonstrated that handle rotation and tilt angles affected pushing strength and should be taken into consideration when evaluating or designing pushing tasks. PMID- 22075259 TI - Residential mobility within England and urban-rural inequalities in mortality. AB - This study is situated within the international literature on geographic health inequalities between urban and rural areas. Using data from the Office for National Statistics Longitudinal Study (ONS LS), this paper assesses the role of residential mobility within England between 1981 and 2001 in explaining geographic inequalities in all-cause mortality between urban and rural Local Authority Districts at the end of the period (deaths occurring between 2001 and 2005). First, the pattern of directly age-standardised death rates (2001-2005) in urban and rural areas of residence in 2001 is examined and compared with the pattern that would have been seen if the observed death/survival of individuals had occurred in their original place of residence in 1981, or in 1991. Secondly, logistic regression is applied to examine whether individuals' residential mobility between urban and rural areas predict the risk of mortality, adjusting for people's socio-demographic characteristics. Findings show that, for this sample, residential mobility 1981-2001 accounts for about 30% of the urban-rural inequalities in mortality observed at the end of the period. LS members who were residentially mobile between urban and rural areas were relatively healthier than long-term urban residents, with better mortality outcomes among rural in migrants. In age-stratified analysis, LS members of working age (20-64 years) moving out of rural areas, and LS members of retirement age (65 years and older) moving into rural areas, were shown to be healthier. Processes of selective migration in and out of rural areas in England are complex and may partly explain urban-rural health inequalities. In terms of varying mortality risk, findings also highlight the possible marginalisation and disadvantage of sub-groups of the rural population. PMID- 22075260 TI - Focus. An emerging conceptual scaffold for NASH. PMID- 22075262 TI - Entecavir in the treatment of chronic hepatitis B in kidney transplantation. PMID- 22075264 TI - In-situ Iberian pig carcass classification using a micro-electro-mechanical system (MEMS)-based near infrared (NIR) spectrometer. AB - Iberian pig (IP) products are gourmet foods highly appreciated at international markets, reaching high prices, because of its exquisite flavors. At present, there aren't practical and affordable analytical methods which can authenticate every single piece put on the market. This paper reports on the performance of a handheld micro-electro-mechanical system (MEMS)-based spectrometer (1600-2400nm) for authentication-classification of individual IP carcasses into different commercial categories. Performance (accuracy and instrumental design) of the instrument was compared with that of high-resolution NIRS monochromators (400 2500nm). A total of 300 carcasses of IPs raised under different feeding regimes ("Acorn", "Recebo" and "Feed") were analyzed in three modes (intact fat in the carcass, skin-free subcutaneous fat samples and melted fat samples). The best classification results for the MEMS instrument were: 93.9% "Acorn" carcasses correctly classified, 96.4% "Feed" and 60.6% "Recebo", respectively. Evaluation of model performance confirmed the suitability of the handheld device for individual, fast, non-destructive, low-cost analysis of IP carcasses on the slaughterhouse line. PMID- 22075263 TI - Commentary to "Intermediate-long term follow-up indicates low risk of recurrence after double HIT endoscopic treatment for primary vesicoureteral reflux (VUR)". PMID- 22075265 TI - Bayesian meta-analysis of the effect of fasting, transport and lairage times on four attributes of pork meat quality. AB - Technological meat quality is a significant economic factor in pork production, and numerous publications have shown that it is strongly influenced both by genetic status and by rearing and slaughter conditions. The quality of meat is often described by meat pH at different times postmortem, as well as by color and drip loss. A meta-analysis based on a database built from 27 studies corresponding to a total of 6526 animals classified was carried out. The purpose of this meta-analysis was to study the effect of fasting, lairage and transport durations on four main attributes of the technological pork meat quality. A Bayesian hierarchical meta-regression approach was adopted. The results of our meta-analysis showed that fasting time had a significant effect on pH measured 24h post-mortem (pHu) and drip loss (DL) measured in longissimus muscle. While, lairage affected only the pHu in semimembranosus muscle. Interestingly, we found that DL was the lone attribute that was affected by transport time and its interaction with fasting time. PMID- 22075266 TI - Dissociable roles for lateral orbitofrontal cortex and lateral prefrontal cortex during preference driven reversal learning. AB - One of the archetypal task manipulations known to depend on frontal-lobe function is reversal learning, where a dominant response must be overridden due to changes in the contingencies relating stimuli, responses, and environmental feedback. Previous studies have indicated that the lateral prefrontal cortex (LPFC), the lateral orbitofrontal cortex (LOFC), the anterior cingulate cortex (ACC), and the caudate nucleus (CN) all contribute to reversal learning. However, the exact contributions that they make during this cognitively complex task remain poorly defined. Here, using functional magnetic resonance imaging, we examine which of the cognitive processes that contribute to the performance of a reversal best predicts the pattern of activation within distinct sub-regions of the frontal lobes. We demonstrate that during reversal learning the LOFC is particularly sensitive to the implementation of the reversal, whereas the LPFC is recruited more generally during attentional control. By contrast, the ACC and CN respond when new searches are initiated regardless of whether the previous response is available, whilst medial orbitofrontal cortex (MOFC) activity is correlated with the positive affect of feedback. These results accord well with the hypothesis that distinct components of adaptable behaviour are supported by anatomically distinct components of the executive system. PMID- 22075268 TI - Modest reversal of metabolic syndrome manifestations with vitamin D status correction: a 12-month prospective study. AB - Numerous cross-sectional studies have noted significant negative associations between circulating levels of 25-hydroxyvitamin D and cardiometabolic risk factors, highlighting potential extraskeletal functions of this sterol hormone. Prospective studies, however, have been limited; and hence, no cause-and-effect relations can be inferred. This study aims to determine whether vitamin D status correction can reverse already established manifestations of the metabolic syndrome (MetS). A total of 59 adult nondiabetic, overweight, and obese Saudis (31 male, 28 female) were prospectively enrolled in this 1-year interventional study. Anthropometry and biochemical evaluation were performed, including determination of serum 25-hydroxyvitamin D, calcium, and phosphorous concentrations, as well as fasting blood glucose and lipid profile. Subjects were advised to regularly expose themselves to sunlight and increase intake of vitamin D-rich foods. All measurements were repeated 6 and 12 months later. At the initial baseline visit, the prevalence of both low high-density lipoprotein cholesterol and hypertension was significantly increased among patients with 25 vitamin D deficiency (P < .05), even after adjusting for sex and body mass index. Overall prevalence of MetS patients by the modified National Health and Nutrition Examination Survey Adult Treatment Panel III definition decreased from 25.2% to 13.0%; and this was largely due to a parallel decrease in the prevalence of low high-density lipoprotein cholesterol, triglycerides, and hypertension. Optimization of vitamin D status through sun exposure and increased intake of a vitamin D-rich diet can lead to an improved cardiometabolic profile, offering a promising nonpharmacologic approach in the prevention of MetS manifestations. PMID- 22075267 TI - Replication and meta-analysis of the gene-environment interaction between body mass index and the interleukin-6 promoter polymorphism with higher insulin resistance. AB - Insulin resistance (IR) is a complex disorder caused by an interplay of both genetic and environmental factors. Recent studies identified a significant interaction between body mass index (BMI) and the rs1800795 polymorphism of the interleukin-6 gene that influences both IR and onset of type 2 diabetes mellitus, with obese individuals homozygous for the C allele demonstrating the highest level of IR and greatest risk for type 2 diabetes mellitus. Replication of a gene environment interaction is important to confirm the validity of the initial finding and extend the generalizability of the results to other populations. Thus, the objective of this study was to replicate this gene-environment interaction on IR in a hypertensive population and perform a meta-analysis with prior published results. The replication analysis was performed using white individuals with hypertension from the Hypertensive Pathotype cohort (N = 311), genotyped for rs1800795. Phenotype studies were conducted after participants consumed 2 diets--high sodium (200 mmol/d) and low sodium (10 mmol/d)--for 7 days each. Measurements for plasma glucose, insulin, and interleukin-6 were obtained after 8 hours of fasting. Insulin resistance was characterized by the homeostatic model assessment (HOMA-IR). In Hypertensive Pathotype, BMI was a significant effect modifier of the relationship between rs1800795 and HOMA-IR; higher BMI was associated with higher HOMA-IR among homozygote CC individuals when compared with major allele G carriers (P = .003). Furthermore, the meta-analysis in 1028 individuals confirmed the result, demonstrating the same significant interaction between rs1800795 and BMI on HOMA-IR (P = 1.05 * 10(-6)). This rare replication of a gene-environment interaction extends the generalizability of the results to hypertension while highlighting this polymorphism as a marker of IR in obese individuals. PMID- 22075269 TI - Resveratrol: is selectivity opening the key to therapeutic effects? PMID- 22075271 TI - Association between thyroid hormone levels, the number of circulating osteoprogenitor cells, and bone mineral density in euthyroid postmenopausal women. AB - In postmenopausal women, an association between reduced bone mineral density (BMD) and increased number of circulating osteoprogenitor cells (COPs) has been found. Although an increased thyroid function is associated with BMD, thyroid hormones stimulate osteoblast function in vitro. We investigated whether thyroid hormones within the reference range were correlated with the number of COPs and stimulate mineralization in vitro. The number of COPs, defined as CD34+/alkaline phosphatase (AP)+ or CD34+/osteocalcin (OCN)+ cells, was quantified by fluorescence-activated cell sorting (FACS) analysis in 150 euthyroid postmenopausal women. Participants underwent measurement of serum free thyroxine (FT4), thyroid-stimulating hormone levels, and femur BMD. CD34+ cells were isolated from healthy volunteers irrespective of AP or OCN expression, and the effect of triiodothyronine (0.5-10 pmol/L)) on their ability to form mineralized nodules in vitro was studied. The number of COPs was highest among women with high-normal FT4 levels (>1.09 ng/dL). The FT4 levels were correlated positively with circulating log-CD34+/AP+ (r = 0.32, P < .001) and log-CD34/OCN+ cells (r = 0.36, P < .001) and inversely with total femur BMD (r = -0.17, P = .036) but not with femoral neck BMD. In a multivariate analysis, the FT4 levels were positively correlated with the number of COPs, independent of age and BMD. The ability of CD34+ cells to form mineralized nodules increased after exposure from low up to high-normal triiodothyronine concentrations (P for trend = .003). Among euthyroid postmenopausal women, high-normal FT4 levels are correlated with an increased number of circulating immature osteoprogenitor cells and a very mild BMD reduction. Exposure of CD34+ cells to physiological triiodothyronine concentrations stimulates mineralization in vitro. PMID- 22075272 TI - The association between triglyceride to high-density-lipoprotein cholesterol ratio and insulin resistance in a multiethnic primary prevention cohort. AB - The objective was to explore the clinical utility of triglyceride (TG) to high density lipoprotein cholesterol (HDL-C) ratio in predicting insulin resistance (IR) in 4 ethnic groups and the relationship between IR and TG/HDL-C in comparison to that with other lipid measures. Apparently healthy Aboriginals, Chinese, Europeans, and South Asians (N = 784) were assessed for sociodemographics, lifestyle, anthropometry, lipids, glucose, and insulin. The homeostasis model assessment of IR was used as a measure of IR. Compared with other lipid parameters, TG/HDL-C was the highest correlate of the homeostasis model assessment of IR (age and sex adjusted) in Aboriginals (r = 0.499, P < .001), Chinese (r = 0.432, P < .001), Europeans (r = 0.597, P < .001), and South Asians (0.372, P < .001). For a 1-unit increase in TG/HDL-C, the odds of being insulin resistant increased about 4 times (odds ratio [OR], 3.95; 95% confidence interval [CI], 1.86-8.42; P < .001) in Aboriginals, 3.4 times in Chinese (OR, 3.44; 95% CI, 1.79-6.62; P < .001), 1.9 times in Europeans (OR, 1.94; 95% CI, 1.00-3.75; P = .049), and 1.8 times in South Asians (OR, 1.77; 95% CI, 0.91-3.45; P = .094) (age, sex, smoking, physical activity, body mass index, and waist circumference adjusted). Receiver operating characteristic curve analyses revealed areas under the curve (95% CI) of 0.777 (0.707-0.847) in Aboriginals, 0.723 (0.647-0.798) in Chinese, 0.752 (0.675-0.828) in Europeans, and 0.676 (0.590-0.762) in South Asians. Optimal cutoffs (sensitivity, specificity) of TG/HDL-C for identifying individuals with IR were 0.9 (93.0%, 51.9%), 1.1 (71.7%, 61.5%), 1.1 (73.5%, 70.9%), and 1.8 (52.0%, 77.9%) in Aboriginal, Chinese, European, and South Asian individuals, respectively. The TG/HDL-C ratio may be a good marker to identify insulin-resistant individuals of Aboriginal, Chinese, and European, but not South Asian, origin. PMID- 22075270 TI - The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes. AB - Vitamin D has been implicated in the pathophysiology of extraskeletal conditions such as hypertension, kidney disease, and diabetes via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. A literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes was performed. Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25-dihydroxyvitamin D(3)-mediated downregulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved beta-cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well designed prospective human interventional studies to definitively assess clinical outcomes. There is a need for more well-designed prospective interventional studies to validate this hypothesis in human clinical outcomes. PMID- 22075273 TI - Short-term walnut consumption increases circulating total adiponectin and apolipoprotein A concentrations, but does not affect markers of inflammation or vascular injury in obese humans with the metabolic syndrome: data from a double blinded, randomized, placebo-controlled study. AB - Long-term consumption of walnuts is associated with lower cardiovascular disease risk in epidemiological studies, possibly through improvements in lipid profile and endothelial function. It remains to be elucidated how soon after initiation of walnut consumption beneficial effects on lipid profile and biomarkers of inflammation or vascular injury can be observed. Fifteen obese subjects (9 men and 6 women; age, 58 +/- 2.5 years; body mass index, 36.6 +/- 1.7 kg/m(2)) with the metabolic syndrome participated as inpatients in a randomized, double blinded, placebo-controlled crossover study involving short-term placebo or walnut-enriched diet (48 g/d for 4 days). Apolipoproteins and markers of inflammation and vascular injury were measured before and after consumption of the experimental diets. Consumption of walnuts was associated with a statistically significant increase in serum apolipoprotein A concentrations (P = .03), but did not affect circulating levels of fetuin A, resistin, C-reactive protein, serum amyloid A, soluble intercellular adhesion molecules 1 and 3, soluble vascular cell adhesion protein 1, interleukins 6 and 8, tumor necrosis factor alpha, E-selectin, P-selectin, and thrombomodulin. Four days of walnut consumption (48 g/d) leads to mild increases in apolipoprotein A concentrations, changes that may precede and lead to the beneficial effects of walnuts on lipid profile in obese subjects with the metabolic syndrome. PMID- 22075274 TI - Systematic validation of specific phenotypic markers for in vitro polarized human macrophages. AB - BACKGROUND: Polarization of macrophages by specific micro-environmental conditions impacts upon their function following subsequent activation. This study aimed to systematically validate robust phenotypic markers for in vitro polarized human macrophages in order to facilitate the study of macrophage subsets in vivo. METHODS: Human peripheral blood monocytes were polarized in vitro with IFN-gamma, IL-4, or IL-10. Similar experiments were performed with TNF, IL-13, dexamethasone, M-CSF and GM-CSF as polarizing stimuli. Phenotypic markers were assessed by flow cytometry and qPCR. RESULTS: IFN-gamma polarized macrophages (MPhi(IFN-gamma)) specifically enhanced membrane expression of CD80 and CD64, IL-4 polarized macrophages (MPhi(IL-4)) mainly upregulated CD200R and CD206, and downregulated CD14 levels, and IL-10 polarized macrophages (MPhi(IL 10)) selectively induced CD163, CD16, and CD32. The expression profiles of the most specific markers were confirmed by qPCR, dose-response experiments, and the use of alternative polarizing factors for each macrophage subset (TNF, IL-13, and dexamethasone, respectively). GM-CSF polarized macrophages (MPhi(GM-CSF)) upregulated CD80 but not CD64 expression, showing a partial phenotypic similarity with MPhi(IFN-gamma), and also upregulated the expression of the alternative activation marker CD206. M-CSF polarized macrophages (MPhi(M-CSF)) not only expressed increased levels of CD163 and CD16, resembling MPhi(IL-10,) but also displayed high levels of CD64. The phenotype of MPhi(M-CSF) could be further modulated by additional polarization with IFN-gamma, IL-4, or IL-10, whereas MPhi(GM-CSF) showed less phenotypic plasticity. CONCLUSION: This study validated CD80 as the most robust phenotypic marker for human MPhi(IFN-gamma), whereas CD200R was upregulated and CD14 was specifically downregulated on MPhi(IL-4). CD163 and CD16 were found to be specific markers for MPhi(IL-10). The GM-CSF/M CSF differentiation model showed only a partial phenotypic similarity with the IFN-gamma/IL-4/IL-10 induced polarization. PMID- 22075276 TI - Heart failure and non-ST-segment elevation myocardial infarction: a review for a widespread situation. AB - Up to 15% of patients with NSTEMI present at admission with heart failure. Scientific evidence for its management is limited but much progress has been made during the last years. Our purpose was to review the last data concerning heart failure in NSTEMI and perform an update on the subject, with the following findings as main highlights. As Killip classes III and IV, Killip class II onset in the context of NSTEMI has also proven bad prognosis significance. Beta-blocker therapy has proven benefit to patients with Killip class II in observational studies and small trials. Angiotensin-converting enzyme inhibitor therapy shows stronger evidence of benefit in patients with heart failure than in patients without it. Eplerenone is indicated for patients with left ventricular dysfunction and heart failure or diabetes mellitus. Implantable cardioverter defibrillators improve survival in patients with severe ventricular dysfunction after a myocardial infarction. Cardiac resynchronization therapy indications must be carefully assessed due to the high rate of implants that do not fulfill guidelines indications. In conclusion, heart failure during a NSTEMI is a common and meaningful situation which warrants careful management and further investigation to reach stronger evidence for clinical recommendations. PMID- 22075277 TI - Antisense therapy in the treatment of hypercholesterolemia. AB - Cardiovascular disease, the leading causes of death worldwide, is a "preventable" pathology, so that accessible and affordable interventions should be established to target the leading risk factors, including hypercholesterolemia. Although statin based therapy is commonplace in primary and secondary prevention, several economical, clinical and safety issues have been raised, so that there is ongoing research into new, safer and more effective agents to be used alone or in combination with existing cardiovascular drugs. Antisense oligonucleotides (ASOs) are a class of short, single-stranded synthetic analogs of nucleic acids that bind to a target mRNA, preventing its translation and thereby inhibiting protein synthesis. Apolipoprotein B-100 (apoB-100) is the major protein moiety of the atherogenic lipoproteins LDL and Lp(a), thus representing the ideal target for antisense therapy. Two anti-apoB100 (i.e., ISIS 301012 and ISIS 147764) and one anti-apolipoprotein(a) (i.e., ASO 144367) have already been developed and tested in some animal and human trials, providing promising results in terms of significant reduction of both LDL and Lp(a). Nevertheless, some safety issues - especially injection-site reactions and potential hepatotoxicity - have also emerged, thereby slowing down the large clinical diffusion of these agents. The present article provides an update on clinical data regarding antisense therapy targeting human apolipoproteins, highlighting the benefits and the potential risks of this innovative therapeutic approach for hypercholesterolemia and hyperlipoproteinemia(a). PMID- 22075275 TI - Methodology for isolation, identification and characterization of microvesicles in peripheral blood. AB - RATIONALE: Analyses of circulating cell membrane-derived microvesicles (MV) have come under scrutiny as potential diagnostic and prognostic biomarkers of disease. However, methods to isolate, label and quantify MV have been neither systematized nor validated. OBJECTIVE: To determine how pre-analytical, analytical and post analytical factors affect plasma MV counts, markers for cell of origin and expression of procoagulant surface phosphatidylserine. METHODS AND RESULTS: Peripheral venous blood samples were collected from healthy volunteers and patients with cardiovascular disease and/or diabetes. Effects of blood sample collection, anticoagulant and sample processing to platelet free plasma (PFP), and MV isolation, staining and storage (freeze-thaw) and cytometer design were evaluated with replicate samples from these populations. The key finding is that use of citrate or EDTA anticoagulants decreases or eliminates microvesicles from plasma by inducing adhesion of the microvesicles to platelets or other formed elements. Protease inhibitor anticoagulants, including heparin, preserve MV counts. A centrifugation protocol was developed in which recovery of isolated MV was high with resolution down to the equivalent light scatter of 0.2 MUm latex beads. Each procedure was systematically evaluated for its impact on the MV counts and characteristics. CONCLUSION: This study provides a systematic methodology for MV isolation, identification and quantification, essential for development of MV as diagnostic and prognostic biomarkers of disease. PMID- 22075278 TI - An overview on cognitive aspects implicated in medical decisions. AB - Cognitive theories on decision making show that individuals often do not decide in a full and rationale way, but instead use cognitive strategies that allow them to overcome the limitations imposed by their limited rationality and the difficulties derived from uncertainty. The first part of the paper will discuss the role of heuristics and biases in medical decision making. This is an interesting field of research since medical decisions must be fast and are often complicated by rapid changes in the patient's clinical condition, uncertain prognosis and unexpected or uncontrollable treatment effects. In such contexts individuals are forced to rely on heuristics to assist them in taking decisions which can sometimes produce cognitive biases. The second part of the paper will be dedicated to discussing ways in which the patients' decisions can be improved. The role of the shared decision making approach will be discussed as well as the role of decision aids. Based on personal information coming from the physical and psychological characteristics and needs of the patient, decision aids give information about specific options and outcomes related to the patient's disease. Provided with a set of well-defined alternatives, patients are assisted in taking their preferred decisions, especially when there is more than one medically reasonable opinion available. Moreover, decision aids facilitate and support the shared decision-making, a process by which patients and physicians discuss and evaluate the alternatives for a particular medical decision together. PMID- 22075279 TI - Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications. AB - Ankylosing spondylitis (AS) is the most frequent and most severe subtype of spondyloarthritis and can be an outcome of any of the other spondyloarthritis subtypes. It primarily affects the axial joints, most notably the sacroiliac joints. Other sites of involvement include the spine, peripheral joints, and entheses (capsules, ligaments, and tendons). Inflammatory enthesopathy progressing to ossification and ankylosis is the pathologic basis for the disease. Extra-articular manifestations vary widely in terms of both frequency and severity. The most common extra-articular manifestations are represented by uveitis, bowel disease, heart, lung, skin, bone and kidney involvement. This review focuses on prevalence and clinical characteristics of the most common extra-articular manifestations in AS, and discuss the diagnosis and therapeutic difficulties that rheumatologists faces when dealing with such manifestations. The advantages of treatment with non-steroidal anti-inflammatory drugs (NSAIDs), especially if continuous use is envisaged, should be weighted against possible gastrointestinal and cardiovascular disadvantages. In the presence of history of gastrointestinal complaints or a high cardiovascular risk, NSAIDs should be used with caution. TNF inhibition has demonstrated effectiveness in the treatment of AS symptoms and all currently available anti-TNF agents appear to have similar efficacy. However, the efficacy of anti-TNF agents varies in the presence of extra-articular manifestations. Etanercept appears to have very little effect on inflammatory bowel disease and limited efficacy on the course of uveitis probably inferior to the monoclonal antibodies infliximab and adalimumab. PMID- 22075280 TI - Clinical approach to severe Clostridium difficile infection: update for the hospital practitioner. AB - The rising incidence of Clostridium difficile (C. difficile) infection or CDI is now a problem of pandemic proportions. The NAP1 hypervirulent strain of C. difficile is responsible for a majority of recent epidemics and the widespread use of fluoroquinolone antibiotics may have facilitated the selective proliferation of this strain. The NAP1 strain also is more likely to cause severe and fulminant colitis characterized by marked leukocytosis, renal failure, hemodynamic instability, and toxic megacolon. No single test suffices to diagnose severe CDI, instead; the clinician must rely on a combination of clinical acumen, laboratory testing, and radiologic and endoscopic modalities. Although oral vancomycin and metronidazole are considered standard therapies in the medical management of CDI, recently it has been demonstrated that vancomycin is the more effective antibiotic in cases of severe disease. Moreover, early surgical consultation is necessary in patients who do not respond to medical therapy or who demonstrate rising white blood cell counts or hemodynamic instability indicative of fulminant colitis. Subtotal colectomy with end ileostomy is the procedure of choice for fulminant colitis. When applied to select patients in a judicious and timely fashion, surgery can be a life-saving intervention. In addition to these therapeutic approaches, several investigational treatments including novel antibiotics, fecal bacteriotherapy and immunotherapy have shown promise in the care of patients with severe CDI. PMID- 22075281 TI - Combining patient administration and laboratory computer systems - a proposal to measure and improve the quality of care. AB - Several approaches to measuring the quality of hospital care have been suggested. We propose the simple and objective approach of using the health related data of the patient administration systems and the laboratory results that have been collected and stored electronically in hospitals for years. Imaginative manipulation of this data can give new insights into the quality of patient care. PMID- 22075282 TI - Should we routinely treat patients with autoimmune/rheumatic diseases and chronic hepatitis B virus infection starting biologic therapies with antiviral agents? Yes. AB - It is well established that hepatitis B virus (HBV) reactivation is common among patients with various hematological or neoplastic diseases who receive chemotherapeutic agents without appropriate antiviral prophylaxis and is associated with significant morbidity and mortality. A number of recent studies have indicated that treatment with anti-tumor necrosis factor (TNF) agents in patients with autoimmune/rheumatic diseases carries a similar risk. Furthermore, appropriate pre-emptive treatment with oral antivirals appears to significantly reduce that risk and should be routinely implemented in clinical practice. Similar data are available for B-cell depleting agents like rituximab from the hematology literature, indicating the need for a similar approach in patients with autoimmune diseases receiving such agents. PMID- 22075283 TI - Should we routinely treat patients with autoimmune/rheumatic diseases and chronic hepatitis B virus infection starting biologic therapies with antiviral agents? NO. AB - Hepatitis B virus (HBV) infection affects a large part of the world population. Different virological HBV categories have been identified and managing strategies for immunosuppressed patients with serological signs of current or past HBV infection has been proposed. Those strategies developed to manage patients in the haematology setting are based on strong evidence. Instead, management of such patients in the rheumatologic setting, especially those treated with biologic response modifiers, is mainly based on data derived by case reports and expert opinions. More data are needed to better manage these patients in case of signs of current or past HBV infection. PMID- 22075284 TI - Treatment of hepatitis C virus infection in patients on maintenance hemodialysis: a single United Arab Emirates center experience. AB - BACKGROUND: Hepatitis C is prevalent among hemodialysis patients. In patients with normal kidney function, treatment with pegylated interferon and ribavirin can lead to eradication of HCV (hepatitis C virus). But the treatment is more problematic in patients with impaired kidney function, in part due to the altered pharmacokinetics of these medications. Despite recent guidelines, the optimal strategy in this group of patients is not well defined. METHOD: In a retrospective study, we reviewed all patients with chronic hepatitis C on hemodialysis treated at Sheikh Khalifa Medical City, in the United Arab Emirates between 2003 and 2009. The aim of our study was to determine the rate of sustained viral response (SVR) and to establish the safety and rate of dropouts in the different treatment regimens used (patients treated with peginterferon only and patients treated with peginterferon and low dose ribavirin). RESULTS: 22 patients were treated during this period. 5 patients received monotherapy with a reduced dose of peginterferon alfa 2b s.c. once weekly while 17 patients were treated with a combination of reduced dose of peginterferon alfa 2a or 2b s.c. once weekly and a low dose ribavirin (200mg/day). A SVR was achieved in 73% (16/22 patients) of the total patient population and in 76% (13/17 patients) in the sub-group of patients treated with a combination therapy. The tolerability was high. No patients had to discontinue their treatment. The use of ESA (erythropoietin stimulating agents) and G-CSF was common in the combination therapy (94% and 53% respectively). CONCLUSION: In our study of patients on hemodialysis with chronic hepatitis C, the use of peginterferon or a combination of peginterferon with a low daily dose of ribavirin achieved a high rate of SVR and the rate of dropout was low after pursuing an aggressive management of side effects. PMID- 22075285 TI - The use of terlipressin in cirrhotic patients with refractory ascites and normal renal function: a multicentric study. AB - Ascites is a common complication of liver cirrhosis, occurring in more than 50 60% of the patients within 10 years of the diagnosis. In 5-10% of patients, ascites cannot be mobilized, or its early recurrence cannot be prevented by medical treatment. This condition is known as "refractory ascites". The use of terlipressin in cirrhotic patients with refractory ascites and normal renal function has not been evaluated. This prospective study was aimed at evaluating whether terlipressin in addition to standard therapy (diuretics plus albumin) might improve the outcome of refractory ascites in cirrhotic patients without HRS. PATIENTS: 26 cirrhotic patients with refractory ascites were prospectively enrolled in this study. All the patients had tense (grade 3) ascites, and 10/26 showed also massive peripheral edema. Patients received maximum diuretic treatment plus albumin and terlipressin. RESULTS: Complete response was seen in 16/26 patients. The higher response to therapy was seen during the 2nd week of treatment. 6 patients showed a decrease of at least two points in the ascites score. No differences in clinical response to treatment were seen according to the etiology of the disease. CONCLUSIONS: In conclusion, our study shows a synergistic effect of terlipressin vs treatment with albumin plus diuretics in patients with refractory ascites. One could speculate that albumin might enhance the vasoconstrictive response to terlipressin, thus contributing to counterbalance the negative effects of systemic vasodilation, which characterizes the hyperdynamic circulation of cirrhotic patients. PMID- 22075286 TI - Does previous hypertension affect outcome in acute heart failure? AB - BACKGROUND: The effect of previous long-term hypertension on mortality in acute heart failure (HF), regardless of blood pressure values, has not been well studied. METHODS: Acute Heart Failure Database (AHEAD) - Czech HF registry enrolled 4153 consecutive patients with acute HF. We excluded severe forms (cardiogenic shock, pulmonary oedema, right HF) and analysed 2421 patients with known presence or absence of previous hypertension. Demographic, clinical and laboratory profile, treatment and mortality rates were assessed and predictors of outcome were identified. RESULTS: Patients with previous hypertension (71.5%) were older, more of female gender, with worse pre-hospitalisation NYHA class, increased incidence of co-morbidities and higher left ventricular ejection fraction (LVEF). Although in-hospital mortality was similar in both cohorts (2.6%), survival at 1, 2 and 3-year was worse in the hypertensive group (75.6%, 65.9% and 58.7% vs. 80.7%, 74.2% and 69.8%; P<0.001). Nevertheless, hypertension was not associated with mortality in multivariate analysis and stronger predictors of outcome were identified (P<0.05): new-onset acute HF [hazard ratio (HR) 0.62] and increased body mass index (HR 0.68) proved to have a protective role. Advanced age (HR 1.86), diabetes (HR 1.45), lower LVEF (HR 1.28) and admission blood pressure (HR 1.54), elevated serum creatinine (HR 1.63), hyponatremia (HR 1.77) and anaemia (HR 1.40) were associated with worse survival. CONCLUSION: Antecedent hypertension is frequent in patients with acute HF and contributes to organ and vascular impairment. However its presence has no independent influence on short- and medium-term mortality, which is influenced by other related co-morbidities. PMID- 22075287 TI - Association between clusters of diseases and polypharmacy in hospitalized elderly patients: results from the REPOSI study. AB - BACKGROUND: Although the association between multimorbidity and polypharmacy has been clearly documented, no study has analyzed whether or not specific combinations of diseases influence the prescription of polypharmacy in older persons. We assessed which clusters of diseases are associated with polypharmacy in acute-care elderly in-patients. METHODS: This cross-sectional study was held in 38 Italian internal medicine and geriatric wards participating in the Registro Politerapie SIMI (REPOSI) study during 2008. The study sample included 1155 in patients aged 65 years or older. Clusters of diseases, defined as two or more co occurring specific chronic diseases, were identified using the odds ratio (OR) for the associations between pairs of diseases followed by cluster analysis. Polypharmacy was defined as the prescription of five or more different medications at hospital discharge. Logistic regression models were run to analyze the association between clusters of diseases and polypharmacy. RESULTS: Among clusters of diseases, the highest mean number of drugs (>8) was found in patients affected by heart failure (HF) plus chronic obstructive pulmonary disease (COPD), HF plus chronic renal failure (CRF), COPD plus coronary heart disease (CHD), diabetes mellitus plus CRF, and diabetes mellitus plus CHD plus cerebrovascular disease (CVD). The strongest association between clusters of diseases and polypharmacy was found for diabetes mellitus plus CHD plus CVD, diabetes plus CHD, and HF plus atrial fibrillation (AF). CONCLUSIONS: The observed knowledge of the relationship among co-occurring diseases and polypharmacy should help to identify and monitor older in-patients at risk of polypharmacy. PMID- 22075288 TI - Relation of functional characteristics and serum alpha-1-antitrypsin (AAT) concentration in patients with PiMM phenotype and chronic obstructive pulmonary disease (COPD). AB - INTRODUCTION: The relation of AAT phenotype and COPD still raises lots of controversy. In this study we aimed to investigate relation lung function characteristics, AAT serum level and COPD in smoking and non smoking population. PATIENTS AND METHODS: This was a prospective non-randomized study in which we evaluated 45 patients with severe (stage IV) COPD. In all patients we determined AAT phenotype, serum AAT levels and lung function tests. We correlated findings in relation to the smoking status. RESULTS: All patients were MM type homozygotes. Serum AAT concentrations were within the reference values, amounting to 1.66g/l in smokers and 1.80g/l in nonsmokers. There was no significant correlation between serum AAT concentrations and lung function parameters. We have observed the higher mean values of ITGV, RV, TLC and RV/TLC in smokers and a statistically significant difference only in ITGV. CONCLUSION: All of the investigated patients with severe COPD were MM type homozygotes with normal plasma level of AAT. There was no significant correlation between the phenotype and severity of COPD. We did not find significant relation of plasma AAT level and lung function impairment. PMID- 22075289 TI - Risk factors for pulmonary hypertension in patients with beta thalassemia intermedia. AB - BACKGROUND: Pulmonary hypertension (PHT) is a common yet poorly understood complication of beta thalassemia intermedia (TI). METHODS: We herein evaluated risk factors for PHT in TI, through comparing 64 TI patients with evidence of PHT by symptomatology and echocardiography (Group I) to age- and sex-matched TI patients without PHT (Group II). Retrieved data included demographics, laboratory parameters, clinical characteristics, and received treatments that may influence PHT development; and reflected the period prior to PHT occurrence in Group I. RESULTS: The mean age of Group I patients at development of PHT was 37.3+/ 10.6years; with 44% being males. Among studied parameters, Group I patients were more likely to be splenectomized (4.9-times), transfusion-naive (3.5-times); hydroxyurea-naive (2.6-times), or iron chelation-naive (2.3-times); and have nucleated red blood cell count >=300*10(6)/l (2.59-times) or a previous history of thromboembolic events (3.69-times). CONCLUSION: TI patients who eventually develop PHT may be identified early on by being splenectomized, having high nucleated red blood cell counts and a previous history of thromboembolism. Prospective clinical trials that evaluate the efficacy, safety, and cost effectiveness of transfusion, iron chelation, and hydroxyurea therapy in preventing PHT in TI are invited. PMID- 22075290 TI - Molecular assay to detect nosocomial fungal infections in intensive care units. AB - SUMMARY: The aims of this study were to determine the incidence of fungal infections in hospital intensive care units and to evaluate a molecular method to detect these infections. MATERIAL AND METHODS: The participants in this study were patients admitted to any of the 10 intensive care units at Nemazi Hospital (Shiraz, southern Iran) between March 2009 and January 2010. Oral and rectal swabs, urine, and sputum samples from patients were checked for fungal colonization. If a nosocomial fungal infection was suspected, clinical samples were examined for fungal infection by culture, direct microscopic examination and real-time PCR. Blood samples were cultured by bedside inoculation onto BACTEC medium. Susceptibility of the isolates to antifungal agents was also determined. RESULTS: Of 870 patients, 550 (63.2%) had Candida colonization in different body sites and 17 (1.9%) had fungal infections. The mortality rate in patients with fungal infections was 58.8% (10 cases). The etiologic agents were Candida albicans, Candida glabrata, Aspergillus flavus, Aspergillus fumigatus and Aspergillus spp. Three C. albicans were found to be resistant to amphotericin B and itraconazole, and one A. fumigatus and two A. flavus were resistant to amphotericin B, ketoconazole and itraconazole. One A. fumigatus was additionally resistant to caspofungin. CONCLUSIONS: Considering the incidence of fungal infections and their high mortality rate, early detection, prompt diagnosis and treatment are critical. Molecular assays can serve as a diagnostic tool to manage patients admitted to the intensive care unit. Antifungal susceptibility testing in different geographical regions can support the choice of prophylaxis and treatment for these patients. PMID- 22075291 TI - Calcium channel antagonist exposures reported to the Poisons Information Center Erfurt. AB - BACKGROUND: We investigated the toxicity profile of the three main groups of calcium channel antagonists (CCA) and compared mixed CCA exposures (CCA plus another drug) with mono CCA exposures. METHODS: All CCA exposures reported to the PIC Erfurt from 2000 to 2009 were analyzed retrospectively. RESULTS: In total, 727 (230 mono and 497 mixed) CCA exposures were registered. Although CCA exposures increased almost twofold from 56 in 2000 to 108 in 2009 their relative frequency to all exposures remained constant. The five CCAs most frequently involved in exposures were the five most frequently prescribed ones in Germany over the same period. In mono and mixed CCA exposures, none or minor symptoms were most often seen with dihydropyridines (mono: 84.7%; mixed: 68.0%) followed by diltiazem (mono: 71.4%; mixed: 62.5%) and verapamil (mono: 57.1%; mixed: 50.0%). Highest rates of moderate (mono: 8.6%: mixed: 20.2%) and severe symptoms (mono: 18.6%; mixed: 23.7%) were observed after verapamil ingestions. Death most frequently occurred with diltiazem (mono: 28.6%; mixed: 12.5%). Rates of moderate symptoms were higher in mixed (13.3%) than in mono CCA exposures (4.8%). No distinct differences were seen regarding the relative frequency of none or minor symptoms, severe symptoms, and death between mono and mixed CCA exposures. CONCLUSION: Exposures to verapamil more often resulted in moderate and severe symptoms than with dihydropyridines. Death mainly occurred with diltiazem. Moderate symptoms were more frequent in mixed than in mono CCA exposures. The frequency of CCAs involved in exposure was related to their prescription. PMID- 22075292 TI - Mucosal healing for predicting clinical outcome in patients with ulcerative colitis using thiopurines in monotherapy. AB - BACKGROUND: Mucosal healing (MH) has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Currently little is known about the efficacy of using thiopurine immunosuppressants in monotherapy to achieve and maintain long-term MH in UC. This study analyzes the efficacy and the clinical impact of MH in patients with UC responded to thiopurine immunosuppressants in the long term. METHODS: An open, observational, cohort study in 20 patients with UC had been in clinical remission in monotherapy with thiopurine immunosuppressants for at least 1 year. MH was assessed by endoscopy. The patients according to the Mayo Endoscopic Score (0 vs 1 and 2), were followed until the end of the study or patient relapse. (according to Truelove and Witts criteria). RESULTS: Mean treatment time was 5.4 years. Twelve (60%) patients presented a Mayo Endoscopic Score of 0. A total of 18 patients were followed up for a median of 27.1 months. After endoscopy, 4 patients (22.2%) presented relapse, with a mean time of 27.5 months for a score >=1 (95% CI; 18.2-36.8) versus 54.3 months for a score=0 (95% CI 47.2-61.3) (p=0.032). CONCLUSIONS: This study shows the efficacy of thiopurine immunosuppressants in achieving mucosal healing in patients who respond to thiopurine immunosuppressants in the long term. We also observe the presence of endoscopy activity is not a rare event in this group of patients and is a predictor of early relapse. PMID- 22075293 TI - Hyperleptinaemia positively correlated with metabolic syndrome in hemodialysis patients. AB - OBJECTIVE: To evaluate the relationship between metabolic syndrome (MetS) and the fasting serum leptin concentration in hemodialysis (HD) patients. PATIENTS AND METHODS: Fasting blood samples were obtained from 101 HD patients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation. RESULTS: Forty-eight patients (47.5%) had MetS. Serum leptin concentrations were positively correlated with MetS (p<0.001). Serum leptin levels correlated with increasing numbers of MetS criteria in HD patients (p=0.001). Univariate linear regression analysis showed that the pre-HD body weight (p<0.001), waist circumference (p<0.001), body mass index (p=0.001), triglycerides (p=0.003), insulin level (p=0.043), and homeostasis model assessment of insulin resistance (p=0.003) positively correlated with serum leptin levels in HD patients and high-density lipoprotein-cholesterol (p=0.016) negatively correlated with serum leptin levels in HD patients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that pre-HD body weight (R(2)=0.175; p<0.001) was the independent predictor of the fasting serum leptin concentration. CONCLUSION: Fasting serum leptin levels positively correlated with MetS and the pre-HD body weight could influence serum leptin in HD patients. PMID- 22075294 TI - Biochemical and ultrasound parameters may help predict the need for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with a firm clinical and biochemical suspicion for choledocholithiasis. AB - BACKGROUND: Prediction of the need for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with suspected choledocholithiasis (CDL) remains a challenging task. AIMS: We aimed to evaluate the predictive value of biochemical and ultrasound parameters and to create a corresponding model for prediction of the need for therapeutic ERCP. METHODS: 203 consecutive patients referred to our center due to a firm clinical and/or biochemical suspicion for CDL. All patients underwent ERCP. Biochemical and ultrasound variables were analyzed. RESULTS: The sample was divided into testing group (103; 50.7%) and validation group (100; 49.3%) which did not differ in their baseline characteristics. Elevated gamma glutamil transaminase (GGT), common bile duct (CBD) diameter and presence of hyperechoic structures in CBD were found to be significant predictors for presence of CBD stones on ERCP (p<0.05) in the testing group. We used these variables to construct a predictive model for the presence of CBD stones on ERCP. The model was tested on a second, validation group of patients using ROC analysis with the area under the ROC curve of 0.81 (%95 CI=0.75-0.86; p<0.001). We identified a threshold (0.86) above which, patients had a high probability (93.1%) for the need for interventional ERCP. CONCLUSION: Our predictive model may help predict the need for therapeutic ERCP in patients with a suspicion for choledocholithiasis. PMID- 22075295 TI - Hoover's sign is a predictor of airflow obstruction severity and is not related to hyperinflation in chronic obstructive pulmonary disease. AB - BACKGROUND: Several phenotypes are described in COPD. OBJECTIVES: To assess if COPD patients with Hoover's sign (HS) belong to a particular phenotype. METHODS: All consecutive COPD patients with varying degree of airflow obstruction that came for lung function testing in one university hospital were prospectively assessed, using clinical and magnetometer detection of HS, body mass index (BMI), St. George's Respiratory Questionnaire for health-related quality of life, six minute-walk test (6MWT) with inspiratory capacity (IC) measurements and expiratory flow limitation (EFL) detection. Previous exacerbations were also reported. RESULTS: 82 patients were studied. Magnetometers confirmed HS in 56 of them, of which 79% (44/56) were detected by clinical assessment. HS (+) patients were older (64 +/- 10 vs 59 +/- 10 years, p=0.03), had a higher BMI (26 +/- 5 vs 23 +/- 4, p=0.04), a lower FEV1 (53% +/- 18% vs 63% +/- 18% pred, p=0.02) and a higher IC decrease at the end of 6MWT, (-19 +/- 2 vs -7 +/- 4% pred, p=0.003). A larger proportion of HS (+) patients also reported severe exacerbations during the past 2 years (39% vs 12% p=0.01). There was no statistical evidence that HS was related to hyperinflation and/or EFL. CONCLUSION: The very simple clinical HS allows identifying a particular population of COPD patients of older age and higher BMI with a more severe airflow obstruction, increased dynamic hyperinflation during exercise and higher exacerbation frequency. These characteristics were not linked to hyperinflation or EFL. PMID- 22075296 TI - Acute Respiratory Distress Syndrome as a presenting manifestation in young patients infected with H1N1 influenza virus. AB - INTRODUCTION: The new strain of influenza A (H1N1) 2009, often referred to colloquially as "swine flu", which was first detected in April 2009, raised to a pandemic of which the impact was not completely predictable. As reported, numerous cases with severe respiratory failure were also seen among young previously healthy people. PATIENTS: In the present study, we report eight cases of influenza A (H1N1) 2009 admitted to our medical intensive care with severe respiratory failure between November and December 2009 and in January 2011. All patients were older than 30 but younger than 50 years, had clinical and radiological evidence of an Acute Respiratory Distress Syndrome (ARDS) and needed invasive ventilatory support. RESULTS: Six of the eight patients had no relevant underlying disease; one had a pre-existing idiopathic lung fibrosis and another had a chronic obstructive pulmonary disease (COPD), an abuse of alcohol and an adiposities grade 3. Four patients needed an extracorporeal membrane oxygenation (ECMO) due to severe respiratory failure with global respiratory insufficiency that could not be treated by conservative ventilatory support. The one patient with a pre-existing lung fibrosis died shortly after lung transplantation despite use of an extracorporeal membrane oxygenation. One other patient died due to a subarachnoidal bleeding under the anticoagulatory regime during ECMO therapy. The adipose COPD-patient died due to septic shock with multiple organ failure without possibility for ECMO support. CONCLUSIONS: The clinical course of severe cases of influenza A (H1N1) 2009-infection is markedly different from the disease pattern seen during epidemics of seasonal influenza. Most of the patients admitted to our intensive care unit due to influenza A (H1N1) 2009 associated ARDS were previously healthy young people. PMID- 22075297 TI - Neurosarcoidosis: report of 30 cases and a literature survey. AB - INTRODUCTION: Neurosarcoidosis accounts for approximately 5% of cases of sarcoidosis. OBJECTIVE: To determine the frequency of Neurosarcoidosis in our setting and analyze the clinical-radiological findings and evolution of 30 patients consecutively diagnosed. METHODS: The medical records of patients with a diagnosis of Neurosarcoidosis were reviewed, and data regarding the clinical features, ancillary tests performed, treatment, and outcome were recorded. We revised the literature to summarize and discuss the previous clinical series of Neurosarcoidosis. RESULTS: It accounted for 6.7% of all cases of sarcoidosis. Seven patients had definite diagnosis and 23 had probable diagnosis. The mean age at onset of Neurosarcoidosis was 48.3 years and 66.7% of patients were women. Neurologic clinical features were the first manifestation of Neurosarcoidosis in 70% of cases. Cranial neuropathy was present in 17 patients and 14 of them had facial palsy. The central nervous system was affected in 10 patients and the peripheral nervous system in 5. Chest disease, the most common extraneurologic manifestation, was present in 20 patients. All patients were treated with corticosteroids, and all those with central nervous system involvement had poor outcome. CONCLUSION: Neurosarcoidosis requires a high degree of suspicion to establish the diagnosis. Central nervous system involvement is associated with a poor prognosis. PMID- 22075298 TI - Low testosterone level in middle-aged male patients with coronary artery disease. AB - BACKGROUND: Endogenous testosterone has been shown to provide a protective role in the development of cardiovascular diseases in men. This study investigated the changes of testosterone level and its relationship to the severity of coronary artery stenosis in middle-aged men with coronary artery disease (CAD). METHODS: Serum testosterone concentration was measured in 87 middle-aged men patients with CAD including stable angina pectoris (SAP), unstable angina pectoris (USAP) and acute myocardial infarction (AMI). All patients underwent coronary angiography and the severity of coronary stenosis was estimated by the Gensini coronary score. The patients with the severity of coronary artery stenosis of less than 50% served as control group. RESULTS: The levels of testosterone in SAP group (488.2 +/- 96.8ng/dl), USAP group (411.6 +/- 128.6ng/dl) and AMI group (365.3 +/- 116.6ng/dl) were significantly lower than that in control group (562.8 +/- 110.2ng/dl) (all p<0.05). When compared with another group among SAP, USAP and AMI groups, the level of testosterone in the AMI group was the lowest, the USAP group was the median while the SAP group was the highest (all p<0.05). There was a significant correlation between angiographic Gensini score and testosterone level (n=87, r=-0.513, p<0.05). Multiple regression analysis found that testosterone and BMI were independent predictors for CAD (testosterone: odds ratio 0.311, 95% confidence interval 0.174-0.512; BMI: odds ratio 1.905, 95% confidence interval 1.116-2.973). CONCLUSION: The present study showed that middle-aged male patients with CAD present a lower level of serum testosterone and the testosterone level was negatively correlated with the severity of coronary artery stenosis. PMID- 22075300 TI - When routine is wrong? The experience of chest radiography. PMID- 22075299 TI - Bile acid malabsorption investigated by selenium-75-homocholic acid taurine ((75)SeHCAT) scans: causes and treatment responses to cholestyramine in 298 patients with chronic watery diarrhoea. AB - BACKGROUND: The liver produces and secretes bile acids into the small intestine. In the small intestine, most of the bile acids are absorbed in the distal ileum with portal vein transportation back to the liver and resecretion (enterohepatic recycling). Increased spillover of bile acids from the small intestine into the colon (bile acid malabsorption) may affect the secretion of colonic water and electrolytes and result in watery diarrhoea. The aim of this study was to investigate the frequency of bile acid malabsorption and treatment responses to cholestyramine with (75)SeHCAT scanning among patients suffering from chronic watery diarrhoea. METHODS: This was a retrospective study that included all patients who received a (75)SeHCAT scan over a five-year period (2004-2009). RESULTS: In total, 298 patients (198 females, 100 men) with a median age of 42 years (range 16-82 years) were investigated. Bile acid malabsorption ((75)SeHCAT retention<15% after seven days) was identified in 201 patients (68%, 95% confidence interval (CI): 62%-73%). Bile acid malabsorption due to ileal dysfunction (Type I) was found in 77 patients, idiopathic bile acid malabsorption (Type II) was found in 68 patients and 56 patients with other conditions had bile acid malabsorption (Type III). Of the 150 patients who were able to take cholestyramine continuously, 108 patients (71%, CI: 63%-78%) reported a positive effect on their bowel habits. CONCLUSIONS: Bile acid malabsorption is a frequent problem in patients with chronic watery diarrhoea. Treatment with bile acid binders was effective regardless of type and severity. PMID- 22075301 TI - The routine chest X-ray is still needed. PMID- 22075302 TI - The health risks of acute exercise should also matter to internal medicine. PMID- 22075303 TI - Chronic physical exercise: beneficial effects overcome risks when correctly prescribed. PMID- 22075304 TI - Helicobacter pylori infection and the risk for cardiovascular disease. PMID- 22075306 TI - A diagnostic study: confidence intervals must be given, and likelihood ratios calculated. PMID- 22075308 TI - Glucose levels at admission and mortality in admitted medical patients: a not so strict association. PMID- 22075309 TI - Prognostic value of B-type natriuretic peptide in patients with left bundle branch block admitted for acute heart failure. PMID- 22075310 TI - Favourable outcome of life-threatening infectious-related haemophagocytic syndrome after combination treatment with corticosteroids and intravenous immunoglobulin infusions. PMID- 22075311 TI - Capillaroscopy as a screening test for clinical antiphospholipid syndrome. PMID- 22075312 TI - Difficulties in identifying Wernicke-delirium. PMID- 22075313 TI - Subcutaneous sarcoidosis: a predictor of systemic disease? PMID- 22075314 TI - Survival after 7 years of follow-up at ninety. The NonaSantfeliu study. PMID- 22075315 TI - The mentor-mentee relationship in academic medicine. PMID- 22075317 TI - Monosensitization and polysensitization in allergic rhinitis. AB - BACKGROUND: Polysensitization is common in patients with allergic rhinitis (AR) and may affect clinical feature. However, there are patients who remain monosensitized. OBJECTIVE: This cross-sectional study aimed at evaluating a large cohort of AR patients to define the percentage and the features of mono- and poly sensitized subjects. METHODS: This observational cross-sectional study included a large group of AR patients: 2415 subjects (1958 males, mean age 24.6 +/- 5 years) were consecutively evaluated. Symptom severity, type and number of sensitizations, and AR duration were considered. RESULTS: 621 patients (25.7%) were monosensitized: 377 to Parietaria, 194 to house dust mites, 19 to birch, 17 to grasses, 12 to molds, 2 to olive, and 1 to cypress. There was no difference between mono- and polysensitized patients concerning the duration of rhinitis (6 +/- 2.14 years vs 6 +/- 3.7). Severity of symptoms was higher in polysensitized patients than in monosensitized (p<0.05); in addition, there was a difference among monosensitized patients: Parietaria-allergy induces the most severe symptoms. CONCLUSION: This study conducted in a large AR population might suggest that monosensitized and polysensitized AR patients could constitute two different categories. In addition, the specific type of allergy may condition the clinical feature. PMID- 22075316 TI - Successful exclusion of blood-borne viral disease in blood donors. AB - BACKGROUND: All blood transfusion services have various rules to insure that blood products are kept safe for transfusion. Donor selection is crucial in providing safe blood. We propose in our study to determine the influence of donor selection on blood safety. METHODS: In this case-control study, donors who were referred to the Qazvin Blood Transfusion Organization during 2007-2009 were selected. Based on a special questionnaire, all blood donors were examined by physicians and every donor was categorized as one of two types of rejected donors (high risk and low risk) or as accepted donors. Data were analyzed by SPSS version 13.0, using chi-square and Fisher's exact tests, where P<0.05 was considered significant. RESULTS: Single donors, the self-employed, the unemployed and students were banned from donation due to high-risk criteria (P<0.0001, 0.003). Female donors were banned from donation due to low-risk criteria. Hepatitis B was more prevalent among cases rejected for donation due to high-risk criteria than among healthy controls (P=0.014); but not so for hepatitis C (P=0.058). Hepatitis B was not significantly more prevalent among those cases rejected for donation due to low-risk criteria, than among healthy cases. CONCLUSION: Those having a history of unsafe sexual conduct and intravenous drug abusers and their spouses are at risk for hepatitis C. Cases rejected for donation due to low-risk criteria were banned from donation to maintain the donors' health, while other cases with low-risk criteria were banned to guarantee the blood recipients' health. PMID- 22075318 TI - Impaired carbon monoxide diffusing capacity as a marker of limited systemic sclerosis. AB - BACKGROUND: As impairment of diffusing capacity for carbon monoxide (DLCO) likely reflects underlying pulmonary vasculopathy in limited systemic sclerosis (lSSc), we examined whether DLCO could help to distinguish secondary from idiopathic Raynaud's phenomenon (iRP). METHODS: We compared pulmonary function test (PFT) results in 145 lSSc patients and 24 age- and sex-matched iRP patients. RP duration at time of PFT was similar in the two groups. RESULTS: DLCO values were low (<80% of predicted) in 106 (73%) of the 145 lSSc patients, and in 69 (71%) of the 97 patients with early lSSc. Interstitial lung disease (ILD) was found in 10% of lSSc patients. DLCO was significantly lower in lSSc than in iRP (72+/-15% versus 89+/-9%, p<0.0001). When evaluated, alveolar capillary membrane conductance (Dm) was markedly lower in lSSc patients without ILD than in iRP patients (45+/-12% versus 71+/-2.5%, p=0.003), although capillary blood volume was not different. DLCO was low in 3 iRP patients (12.5%). The sensitivity and specificity of low DLCO values for early lSSc diagnosis in patients with Raynaud's phenomenon were 71% and 87.5%, respectively. Sensitivity was similar to that of anti-centromere-antibodies (75%) and nailfold capillary abnormalities (81%). A DLCO cutoff of <70% had a sensitivity and specificity of 41% and 100%, respectively. In multivariable analysis, age and low DLCO were the only independent predictors of death; the hazard ratio for DLCO <=50% was 7.9 (95% CI 2.3-26, p=0.0007). CONCLUSION: Isolated DLCO impairment is significantly more frequent in patients with lSSc than in patients with idiopathic iRP. DLCO measurement could be a useful diagnostic tool for lSSc. PMID- 22075319 TI - Removal of retrievable vena cava filters in routine practice: a multicenter study. AB - Vena cava filters (VCFs) are used to prevent pulmonary embolism when anticoagulation is contraindicated or in the event of progression of thrombosis despite adequate anticoagulation. Retrievable VCFs provide a potential advantage over permanent VCFs, but the appropriateness of their use and the frequency with which they are removed is not well established. OBJECTIVES: Document the indications for insertion of retrievable VCFs, filter removal in hospital practice. METHODS: Observational study conducted in three academic medical centers. Consecutive patients undergoing retrievable VCF insertion were identified. Clinical data was extracted from the patients' charts and follow up data were obtained from treating physicians after discharge. RESULTS: 300 patients were studied. The indication for filter insertion was acute bleeding (46.1%) or surgery (24.2%) in patients with acute thrombosis, prevention of venous thromboembolism in trauma (13.3%), potential bleeding in patients with deep vein thrombosis (9.1%) thromboembolism while on adequate anticoagulation (5.7%) and other (1.3%). 21 (7%) filters were removed. An unsuccessful attempt at retrieval was undertaken in a further 9 (3%) patients. CONCLUSIONS: The use of retrievable VCFs was appropriate, with the possible exception of their prophylactic use in major trauma. The majority of VCFs were not removed, for reasons that are not apparent. PMID- 22075320 TI - Renin-angiotensin system inhibitors reduce the progression of mesangioproliferative glomerulonephritis: 10 year follow-up. AB - BACKGROUND: Proteinuria is a common presentation of mesangioproliferative glomerulonephritis (MsPGN). No studies are available on the long-term effect of treatment by renin-angiotensin system (RAS) inhibitors on renal outcome in MsPGN patients. This study prospectively evaluates the effects of RAS inhibitors on renal outcome in patients with low risk MsPGN followed up for 10 years using historical patients with similar features at the time of presentation as untreated controls. METHODS: ENDPOINTS: decrease of basal proteinuria>20% and loss>20% of basal glomerular filtrate rate (GFR) at the end of first year of observation. The patients were re-evaluated bimonthly during the first year and every 6 months thereafter. RESULTS: Twenty-five patients fulfilled the selection criteria. After one year follow-up 19 patients reached the endpoint of proteinuria and no patient reached the endpoint of GFR. No significant change in blood pressure levels (BP) and GFR was registered, by contrast daily proteinuria decreased significantly (p<0.001), falling by 29% at sixth month and 47% at the end of the follow-up. The historical control group consisted of 15 untreated patients seen between 1987 and 1992. The two-way analysis of variance for repeated measures showed greater values of GFR (p<0.001) and lower levels of daily proteinuria (p<0.001) in treated patients as compared to untreated controls. CONCLUSIONS: This 10-year follow-up study indicates that the early treatment with RAS inhibitors at low doses favourably influences the long-term renal outcome in proteinuric patients with MsPGN. Limitations were the small sample size and lack of randomization. PMID- 22075322 TI - Tuberculous cerebral vasculitis: retrospective study of 10 cases. AB - BACKGROUND: Tuberculous cerebral vasculitis is a complication of tuberculous meningitis. This study was undertaken to determine the epidemiological characteristics, context, diagnostic means and outcomes under treatment of tuberculous cerebral vasculitides. METHODS: All consecutive patients diagnosed with tuberculous cerebral vasculitis were identified from the databases of three Internal Medicine, one Neurology and one Infectious Disease Departments in three suburban Parisian hospitals. RESULTS: We describe 10 cases: five men and five women (median age 33.5 [range: 27-55] years). Two were infected with the human immunodeficiency virus. Nine patients had tuberculous meningitis, eight with extraneurological involvement. The following manifestations led to the diagnosis: motor deficit, acute confusional state, headaches, involvement, coma and/or seizures. The cerebral vasculitis revealed tuberculosis in three patients, but tuberculosis was already known when vasculitis was diagnosed for the seven others. The cerebral computed-tomography scan showed cerebral infarctions in five patients, hydrocephalus and tuberculomas in four, while magnetic resonance imaging detected infarctions and leptomeningitis in nine patients, pachymeningitis in one, hydrocephalus and tuberculomas in seven. Therapy combined antituberculous agents with oral corticosteroids for all patients, preceded by a methylprednisolone pulse for five patients. Outcome was favorable for nine patients. CONCLUSION: We described the non-negligible frequency of tuberculous cerebral vasculitides, their clinical manifestations and their potential severity, and the diagnostic and monitoring contributions of magnetic resonance imaging and magnetic resonance angiography. PMID- 22075321 TI - The predictive value of mean platelet volume in differential diagnosis of non functional pancreatic neuroendocrine tumors from pancreatic adenocarcinomas. AB - OBJECTIVE: The aim of the present study is to evaluate in a retrospective manner the diagnostic value of mean platelet volume (MPV) in pancreatic adenocarcinomas and pancreatic neuroendocrine tumors (PNETs). PATIENTS AND METHODS: A total of 92 patients, who were admitted for pancreatic adenocarcinoma (n=76) and PNET (n=16) between March 2007 and December 2009, were analyzed retrospectively for demographics and clinical information. RESULTS: Thirty-nine patients (51.3%) had a resectable, whereas 37 patients (48.7%) had an unresectable pancreatic adenocarcinoma. Nine patients (56.3%) had a non-functional PNET, 6 patients (37.5%) had an insulinoma, and the remaining one patient had a gastrinoma. The mean age was 59.3+/-10.5 for pancreatic adenocarcinomas and 45.1+/-10.6 for PNETs. The mean age at diagnosis was significantly higher in patients with pancreatic adenocarcinomas than the patients with PNET (p<0.001). Preoperative mean hemoglobin levels were significantly lower in patients with pancreatic adenocarcinoma than those with PNET (12.4+/-1.8g/dl vs 13.7+/-2.2g/dl), (p<0.013). The preoperative median MPV levels were significantly lower in patients with PNET 7.8fL (7.2-9.4) than in patients with pancreatic adenocarcinomas 8.6fL (6.6-13.5), (p<0.014). In subgroup analysis, a significant difference in MPV levels was mainly caused by the difference between pancreatic adenocarcinomas and non-functional PNETs (p=0.017). The cut-off value of MPV level for detection of PNETs was calculated as<=7.8fL using ROC analysis [Sensitivity: 66.7%, specificity: 75.9%, AUC: 0.734 (0.587-0.880) p=0.022]. In logistic regression analysis, independent predictive factors for determining PNETs in the differential diagnosis of pancreatic adenocarcinomas were calculated as age (OR=0.068, 95% CI: 0.012-0.398), Ca 19-9 (OR=0.039, 95% CI: 0.006-0.263), MPV (OR=0.595, 95% CI: 0.243-1.458), and hemoglobin (OR=1.317, 95% CI: 0.831 2.086). CONCLUSION: Age, Ca 19-9, MPV, and hemoglobin levels have diagnostic value for distinguishing PNETs from pancreatic adenocarcinomas. PMID- 22075323 TI - A case of an extremely large accessory bone with unusual sutures and foramina parietalia permagna in multiple premature craniosynostoses. AB - BACKGROUND: Within the entity of craniofacial malformations premature craniosynostoses represent the majority of cases. They originate from disturbances in the ossification process, resulting in an osseous closure of cranial sutures ahead of time. Depending on severity and number of the affected sutures, a local or general growth inhibition of the skull follows. In the rare instance of accessory bones along these affected sutures, they may interfere with diagnostics and therapy. PATIENT: This clinical report describes the case of a seven-month-old male infant with multiple craniosynostoses, an extraordinary large accessory median calvarial bone, two foramina parietalia permagna and a submucosal cleft palate. Chromosomal and genetic analysis did not reveal potential mutations. RESULTS: The osseous abnormalities were diagnosed and displayed by three-dimensional computed tomography. The sequential surgical treatment consisted of occipital remodelling at seven months of age and frontoorbital advancement at fourteen months. CONCLUSION: This rare anatomical variation of the cranial bones - superimposed by multiple premature craniosynostoses - demonstrates the necessity of accurately conducted preoperative diagnostics for appropriate surgical planning. Knowledge, and precise medical examination of potential anatomical variations facilitate the planning and secure performance of surgery as well as its outcome. PMID- 22075324 TI - A longitudinal study on the osteoarthritic change of the temporomandibular joint based on 1-year follow-up computed tomography. AB - This study aims to report the results of a 1-year computed tomographic (CT) follow up of 54 temporomandibular joints (TMJs) affected by osteoarthritis (OA) and to provide longitudinal information on changes in OA and its relationship with clinical signs and symptoms. TMJ OA was diagnosed by history, clinical and CT examinations. The second CT examination was done after about 1 year of conservative treatment. Joints were divided into three groups labeled as no change, improved CT, and worsened CT groups depending on the longitudinal bony change of OA observed in the CT. The sex distribution, mean age, joint noise, subjective pain, joint tenderness, masticatory muscle tenderness, and improvement of subjective symptoms were not different between the groups at the first and second examination, while maximum (p < 0.01) and painless mouth opening range (p < 0.001) at the first examination were both smaller in the worsened CT group. Although the clinical signs and symptoms of OA were improved in 40 joints, 74.1%, at 7.2 +/- 4.6 months, the amount if improvement did not differ between the groups. The extent of the destructive change of the condyle was highest in the improved CT group at the first (p < 0.001) and in the worsened CT group at the second examination (p < 0.001). These results imply that the prognosis of OA changes may be independent of the clinical signs and symptoms. More specific longitudinal information as regards OA changes of the TMJ based on a larger sample and a longer follow-up period would be likely to provide a better understanding of TMJ OA. PMID- 22075325 TI - Preoperative three-dimensional reconstruction in vascularized fibular flap transfer. AB - OBJECTIVE: The objective of this study was to investigate the added value of preoperative computerized tomographic angiography (CTA) and three-dimensional reconstruction of the lower limb in vascularized fibular flap transfer. METHODS: Eighteen patients who underwent mandibular or maxillary reconstruction with a vascularized fibular flap were studied retrospectively by image analysis. The original DICOM data of preoperative CTA were analysed and applied to the reconstruction of the lower limb using SimPlant Pro software (version 11.04). RESULTS: The course of the peroneal artery in 17 patients was the same except for one patient. The peroneal artery originates from the posterior tibial artery. The original external diameters of the peroneal artery were 2.99 +/- 0.64 mm. The perpendicular lengths from fibular head to the origin of the peroneal artery and to the fibular perforator vessel were 42.88 +/- 8.84 mm and 174.55 +/- 25.62 mm, respectively. CONCLUSION: The course of peroneal artery was relatively invariable, its original external diameter was thick. Preoperative CTA and three dimensional reconstruction of the lower limb, which are noninvasive, accurate and direct-viewing methods, play an important, preoperative role in vascularized fibular flap transfer for lower limb vascular assessment. PMID- 22075326 TI - Maxillary alveolar ridge reconstruction with monocortical fresh-frozen bone blocks: a clinical, histological and histomorphometric study. AB - BACKGROUND: This investigation is a clinical and histological assessment of fresh frozen bone use in the reconstruction of maxillary alveolar ridges. The study evaluates the effectiveness of this material as a bone filler prior the placement of dental implants. PATIENTS AND METHODS: Sixteen patients with atrophic maxillary ridges underwent maxillary reconstruction with fresh-frozen tibial human block grafts prior to implant placement. Sampling procedures were carried out 4, 6 and 9 months later when a bone core was removed from the grafts for histological and histomorphometric analysis. RESULTS: Eighteen blocks were placed, and each patient received either 1 or 2 blocks. During the sampling procedures, all of the grafts were found to be firm in consistency, well incorporated, and vascularized. A total of 34 implants were placed into the grafts with a minimum of 40-Newton-cm torque in all cases. The follow-up period ranged from 18 to 30 months. No implants were lost. The histological analysis revealed vital bone with mature and compact osseous tissue surrounded by marrow spaces. CONCLUSION: Bone allografts can be used successfully as graft material for the treatment of maxillary ridge defects. This type of bone graft can be used safely in the areas of implant placement as a suitable alternative to autogenous grafts. PMID- 22075327 TI - De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome. AB - Acute megakaryoblastic leukemia (AMKL) is a type of acute myeloid leukemia (AML), in which majority of the blasts are megakaryoblastic. De novo AMKL in adulthood is rare, and carries very poor prognosis. We here report a 45-year-old woman with de novo AMKL with BCR/ABL rearrangement and der(16)t(1;16)(q21;q23) translocation but negative for t(9;22) Ph chromosome. Upon induction chemotherapy consisting of homoharringtonine, cytarabine and daunorubicin, the patient achieved partial hematological remission. The patient was then switched to imatinib plus one cycle of CAG regimen (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor), and achieved complete remission (CR). The disease recurred after 40 days and the patient eventually died of infection. To the best of our knowledge, this is the first report of de novo AMKL with p210 BCR/ABL and der(16)t(1;16)(q21;q23) translocation but not t(9;22) Ph chromosome. PMID- 22075328 TI - The importance of physicians' risk perception in osteoporosis treatment decision making. AB - Recent physicians' guidelines for postmenopausal osteoporosis emphasize the use of fracture-risk scores. To determine whether adherence to the guidelines has potential to improve targeting of care, we examined survey results from a random sample of US primary care physicians prior to the new guidelines. Survey measures included physicians' knowledge, attitudes, and perceived barriers to care. Physicians' estimates of 5-yr and lifetime absolute hip fracture risks and their treatment decisions were examined for patient vignettes depicting postmenopausal women of varying ages, weights, and bone mineral density (BMD) results. The 360 US physician respondents were accurate in their estimates of lifetime fracture risk for all 4 vignettes, but overestimated 5-yr hip fracture risk by a factor of 10 or more; 36-45% of the physicians recommended treatment for patients whose history and BMD placed them below guideline-recommended treatment thresholds, and 5-yr risk estimates were strongly associated with prescription treatment decisions for 2 of 3 such vignettes (both p<0.01). Other potential barriers to care include medication costs and adverse effects. Our findings suggest efforts to improve targeting of osteoporosis care are appropriately addressing physicians' risk estimation. Evidence from other conditions suggests these efforts must be intensive and available at the point of care. PMID- 22075329 TI - Personal and parental nativity as risk factors for food sensitization. AB - BACKGROUND: Immigrants to developed countries have low rates of aeroallergen sensitization and asthma, but less is known about both food allergy and the role of parental immigration status. OBJECTIVE: We sought to evaluate the relationship between personal and parental nativity and the risk of food sensitization. METHODS: Three thousand five hundred fifty subjects less than 21 years old from the Nation Health and Examination Survey 2005-2006 were included. Odds ratios (ORs) were generated by using logistic regression, which adjusted for race/ethnicity, sex, age, and household income and accounted for the complex survey design. Nativity was classified as US-born or foreign-born, and the age of immigration was estimated. Head-of-household nativity was used as a proxy for parental nativity. Food sensitization was defined as at least 1 specific IgE level of 0.35 kU/L or greater to milk, egg, or peanut. Aeroallergen-specific sensitizations and the presence of asthma, allergic rhinitis, or eczema were also assessed. RESULTS: Compared with those born outside the United States (US), US born children and adolescents had higher odds of sensitization to any food (OR, 2.05; 95% CI, 1.49-2.83; P < .001). Among the foreign-born group, those who arrived before 2 years of age had higher odds of food sensitization than those who arrived later (OR, 2.68; 95% CI, 1.19-6.08; P = .02). Within the US-born group, in contrast, children of immigrants were at the highest risk (OR, 1.53; 95% CI, 1.05-2.24; P = .02). CONCLUSION: Although foreign-born children and adolescents are at lower risk of food sensitization compared with those born in the US, among those born in the US, the children of immigrants are at the highest risk. PMID- 22075331 TI - Postoperative regional distribution of pulmonary ventilation and perfusion in infants with congenital diaphragmatic hernia. AB - BACKGROUND/PURPOSE: Advances in management of patients with congenital diaphragmatic hernia (CDH) have improved mortality rates but with a risk of increased pulmonary morbidity. The prognosis for CDH survivors remains difficult to predict owing to the lack of adequate methods. We used single photon emission computed tomography (SPECT) to measure the regional distribution of ventilation and perfusion in CDH infants to quantify the degree of lung function impairment and relate it to neonatal clinical disease severity. METHODS: Single photon emission computed tomography was performed in 12 CDH infants at the mean age of six months. Ventilation and perfusion were traced with 5 MBq Technegas and technetium-labelled albumin macro-aggregates, respectively. Neonatal clinical data collected during the patient's stay in the pediatric intensive care unit was correlated with the SPECT data. RESULTS: Single photon emission computed tomography revealed varying degrees of ventilation-perfusion abnormalities which correlated with the presence of pulmonary artery hypertension, days on ventilator and days on extracorporeal membrane oxygenation. CONCLUSIONS: The grade of clinical disease severity in infants following CDH repair is closely related to the ventilation-perfusion abnormality as seen using SPECT. The persistence of pulmonary artery hypertension into the postoperative neonatal period appears to be an important pathophysiological factor related to ventilation-perfusion abnormalities. Single photon emission computed tomography provides valuable clinical information for patient follow-up. PMID- 22075330 TI - A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. AB - BACKGROUND: Atopy and plasma IgE concentration are genetically complex traits, and the specific genetic risk factors that lead to IgE dysregulation and clinical atopy are an area of active investigation. OBJECTIVE: We sought to ascertain the genetic risk factors that lead to IgE dysregulation. METHODS: A genome-wide association study (GWAS) was performed in 6819 participants from the Framingham Heart Study (FHS). Seventy of the top single nucleotide polymorphisms (SNPs) were selected based on P values and linkage disequilibrium among neighboring SNPs and evaluated in a meta-analysis with 5 independent populations from the Cooperative Health Research in the Region of Augsburg cohort, the British 1958 Birth Cohort, and the Childhood Asthma Management Program cohort. RESULTS: Thirteen SNPs located in the region of 3 genes, FCER1A, signal transducer and activator of transcription 6 (STAT6), and IL13, were found to have genome-wide significance in the FHS cohort GWAS. The most significant SNPs from the 3 regions were rs2251746 (FCER1A, P = 2.11 * 10(-12)), rs1059513 (STAT6, P = 2.87 * 10(-8)), and rs1295686 (IL13, P = 3.55 * 10(-8)). Four additional gene regions, HLA-G, HLA-DQA2, HLA-A, and Duffy blood group, chemokine receptor (DARC), reached genome-wide statistical significance in a meta-analysis combining the FHS and replication cohorts, although the DARC association did not appear independent of SNPs in the nearby FCER1A gene. CONCLUSION: This GWAS of the FHS cohort has identified genetic loci in HLA genes that might have a role in the pathogenesis of IgE dysregulation and atopy. It also confirmed the association of the known susceptibility loci FCER1A, STAT6, and IL13 for the dysregulation of total IgE. PMID- 22075332 TI - Is complete resection of the aganglionic bowel in extensive total aganglionosis up to the middle ileum always necessary? AB - BACKGROUND/PURPOSE: Total colonic aganglionosis is an unusual form of Hirschsprung disease, reflected by the small number of published case studies. The goal of this study was to analyze our cases of the last 22 years and report on our experience with 3 cases of extended total aganglionosis proximal to the middle ileum in which remaining aganglionic bowel was left in situ. MATERIALS AND METHODS: In a period of 22 years (from January 1988 to April 2010), we operated on 15 children with total aganglionosis. These children were among 163 children with Hirschsprung disease. In 3 patients with extended aganglionosis proximal to the middle ileum, remaining aganglionic bowel was left in situ. Data were collected from the medical records, including each patient's demographics, medical history, primary treatment, complications, and follow-up. RESULTS: Eleven of the 15 children received an ileostomy as first treatment, and 4 children underwent a primary Duhamel procedure. Early postoperative complications included an abscess after an open procedure in a patient with trisomy 21 syndrome and an incorrect leveling resection that required an ileostomy. There were 2 deaths at 6 and 16 months postoperatively. The mortality rate was 13.3%. Of the 15 patients, 7 (46%) presented with at least 1 episode of postoperative enterocolitis, and only 2 of these patients had more than 3 episodes. We treated 3 patients with extended aganglionosis up to midileum (20%) in which the proximal resection level was in the aganglionic segment of ileum at the level of the ileostomy. The ileostomies were shown to be functioning satisfactorily before the pull through, so going more proximal to the ileostomy might have meant that the patient would present short bowel problems. These 3 patients had good bowel function postoperatively. CONCLUSION: In principle, resection of the aganglionic bowel is mandatory to relieve obstruction and subsequent complications. There are situations, however, where the complications of a short bowel begin to outweigh the benefits of resection. In these cases, leaving remaining aganglionic bowel in situ may be an advantageous option for the patients with total aganglionosis extending to the midileum whose ileostomy functions well. PMID- 22075333 TI - Neonatal acute appendicitis: a proposed algorithm for timely diagnosis. AB - BACKGROUND: Neonatal appendicitis (NA) is a rare disease with a high mortality. The diagnosis has never been reported preoperatively and is notoriously difficult to make. METHODS: Charts since 1995 were retrospectively reviewed for discharge or death diagnoses of appendicitis in neonates younger than 28 days. We report 3 cases of NA seen at our institution during this period. RESULTS: All 3 infants were previously well, born at term, and presented with signs consistent with abdominal sepsis. The first 2 diagnoses were not made until autopsy. The third case survived after having an urgent computed tomographic scan, exploratory laparotomy, and appendectomy. DISCUSSION: The literature summarizing common presenting features of NA is reviewed. We present an algorithm to guide the workup of these neonates to facilitate earlier diagnosis and potentially improve outcomes. PMID- 22075334 TI - Strategy for management of retroperitoneal tumors with caval tumor thrombus. AB - The surgical management of retroperitoneal tumors extending into the inferior vena cava (IVC) can be challenging. Although Wilms' tumor is the most common retroperitoneal tumor extending into the IVC, one must approach these tumors systematically as other diagnoses are possible. We present 4 consecutive cases of retroperitoneal tumors with IVC extension as a basis for a management strategy in approaching these patients. Despite similar presentations, these cases illustrate the nuances in surgical management and need for multidisciplinary care with the pediatric oncologists, pediatric surgeons, and pediatric cardiac surgeons. PMID- 22075335 TI - Vaginal tumors in childhood: the experience of St. Jude Children's Research Hospital. AB - BACKGROUND/PURPOSE: The aim of this study was to retrospectively analyze the clinical presentation, histology, treatment, and outcomes of children with vaginal tumors who were treated at a single institution. METHODS: A retrospective review of medical records and pathologic materials of all children with vaginal tumors treated at St Jude Children's Research Hospital between 1970 and 2009 was conducted. RESULTS: Eighteen patients (median age, 3.7 years; range, 0.1-15 years) were identified. Three different histologies were found: rhabdomyosarcoma (RMS; n = 13), germ cell tumor (n = 3), and clear cell adenocarcinoma (n = 2). Bleeding or blood-tinged discharge was the most common clinical presentation (66%), followed by a protruding mass (39%). Vaginal and uterine salvage was 44.4% (8 of 18 patients). Thirteen patients (72.2%) remain disease-free, with a median follow-up of 23.2 years (range, 2-39 years). Four patients (22.2%) died of disease progression (1 RMS, 2 germ cell tumor, and 1 clear cell adenocarcinoma), and 1 patient with RMS died of colon cancer 12 years after the primary diagnosis had been made. CONCLUSIONS: Vaginal tumors are extremely rare in the pediatric population. Early recognition of symptoms like bleeding and a protruding vaginal mass may prevent morbidity and mortality. Our findings confirm the good prognosis of vaginal RMS. PMID- 22075336 TI - Abdominal inflammatory myofibroblastic tumor a clinicopathologic study with reappraisal of biologic behavior. AB - BACKGROUND AND PURPOSE: Inflammatory myofibroblastic tumor (IMT) is a proliferative lesion of controversial nosology and uncertain prognosis. In an attempt to acquire further understanding of pathogenesis and biologic behavior, we surveyed abdominal IMTs managed over the last 12 years at a single institution. METHODS: Intra-abdominal IMTs treated between 1995 and 2007 were reviewed concerning demographic, clinical, and pathologic features as well as therapeutic management and outcome. All specimens were reevaluated by histologic examination and immunohistochemistry. RESULTS: There were 7 patients (4 males; age range, 28 days to 14 years). Five lesions were located in alimentary tract: 1 gastric presenting with bleeding, 1 hepatic presenting with a thoracic wall mass, 1 pancreatic and 2 colonic presenting with obstructive symptoms. One splenic IMT was found incidentally. The remaining case arose from the adrenal gland and presented with a palpable mass. The gastric and adrenal IMTs had evidence of a previous or concomitant infectious setting. Five lesions were excised. The pancreatic IMT underwent a drainage procedure followed by steroid administration, and the hepatic lesion received antibiotics. Histopathology revealed characteristic findings of IMT. Expression of anaplastic lymphoma kinase was negative in all cases. At a median follow-up of 6 years (range, 3-15), all children were asymptomatic with no recurrences. The hepatic and pancreatic IMT displayed complete and near total regression, respectively. CONCLUSION: A benign behavior of abdominal IMTs was observed even in patients not undergoing surgical excision. Although IMT remains a surgical disease, a conservative approach may be reasonable in select cases. PMID- 22075337 TI - Percutaneous sclerotherapy in neonatal and infant head and neck lymphatic malformations: a single center experience. AB - PURPOSE: To evaluate the clinical outcomes of percutaneous sclerotherapy for congenital head and neck lymphatic malformations in our institution. MATERIALS AND METHODS: Over a 7-year period, 17 children (10 M, 7 F) mean age 5.8 months (5 days to 13 months) underwent 49 sclerotherapy procedures for congenital head and neck malformations. The imaging and clinical records were reviewed for each patient. Ten of 17 had macrocystic disease; 7 of 17 had microcystic disease. Imaging response was categorized by volume reductions of 0% to 25%, 25% to 50%, 50% to 75%, or 75% to 100%. A concentration of 10 mg/mL doxycycline was used routinely via catheter in 3 instillations with a dose range of 50 to 500 mg per session as per our standard protocol in 17 of 17 patients. In more recent patients, systemic doxycycline levels were obtained after instillations. Additional treatments included direct injection doxycycline (10/17), instillation of absolute ethanol (7/17) or sodium tetradecyl sulfate (4/17), or a combination of these methods. RESULTS: Imaging improvement of >= 76% was noted in 11 of 17. Of these, 8 of 11 had macrocystic disease. Four of 17 had 51% to 75% resolution, of which 3/4 were mixed. Two of 17 children had 25% to 50% resolution with a mixed lesion. Seven of 49 peri-procedural complications: hemolytic anemia in 2 infants, hypoglycemic and metabolic acidosis in 3 neonates aged 7 to 10 days, transient hypotension during absolute alcohol instillation in 1 neonate, and self limiting skin excoriation secondary to peri-catheter leakage of doxycycline in one neonate. Neonates prone to these systemic complications had doxycycline doses of greater than 250 mg and resulted in serum levels of >5 MUg/mL but as high as 21 MUg/mL. Delayed neural complications occurred in 7 of 49 procedures, Horner's syndromes in 4 of 49 procedures, transient left lip weakness in 1 of 49 procedures, right facial nerve palsy in 1 of 49 procedures, and transient left hemidiaphragm paralysis in 1/49 procedures. CONCLUSION: Our experience with catheter directed doxycycline sclerotherapy provides excellent results for large macrocystic head and neck lymphatic malformations. Microcystic and mixed lesions continue to provide a therapeutic challenge. PMID- 22075338 TI - Total oxidant status and oxidative stress are increased in infants with necrotizing enterocolitis. AB - BACKGROUND: Oxidative stress has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). In this study, we compared the global oxidant/antioxidant status by measuring total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in preterm infants with NEC and with control preterms. METHODS: Forty-one preterm neonates with NEC (stage 1 [group 1; n = 23] and stages 2 and 3 [group 2; n = 18]) and age-matched 36 healthy preterm controls (group 3) were included in this study. Blood samples were obtained both at the time of NEC diagnosis and 72 hours after for the evaluation of TAC and TOS. Serum levels of TAC, TOS, and OSI in patients with NEC were compared with controls. RESULTS: Demographic characteristics were comparable in all 3 groups. Preterm neonates in group 2 (with stages 2 and 3 NEC) had the highest TOS levels and OSI (P < .001 vs both groups 1 and 3). There was no difference in TAC levels among the groups (P = .26). CONCLUSIONS: Our findings demonstrated that although TAC levels were similar in all 3 groups, oxidant stress mechanisms were activated in preterm neonates with definite NEC (stages 2 and 3 NEC). Premature neonates with increased levels of TOS and OSI were associated with severity of NEC. PMID- 22075339 TI - Melatonin ameliorates necrotizing enterocolitis in a neonatal rat model. AB - INTRODUCTION: We designed the present study to evaluate the efficacy of melatonin (M) on the severity of necrotizing enterocolitis (NEC) in a neonatal rat model. MATERIALS AND METHODS: Immediately after birth, pups were weighed and randomized into 3 groups: NEC, NEC + M, and control. Necrotizing enterocolitis was induced by enteral formula feeding and exposure to hypoxia after cold stress at 4 degrees C and oxygen. The NEC + M group received 10 mg/kg M daily for 3 days after the first day of the NEC procedure. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. Blood samples were also obtained from the pups. RESULTS: The mortality rate and weight loss were highest in the NEC group. Malondialdehyde and protein carbonyl content were significantly increased, whereas superoxide dismutase and glutathione peroxidase were decreased in the NEC-treated pups. Melatonin prevented these changes, with these values being similar to control levels in the NEC + M group. Nitrate plus nitrite levels and serum tumor necrosis factor alpha and interleukin-1beta were increased in the NEC group, and histopathologic injury score in the NEC group was significantly higher than that in the NEC + M group. CONCLUSION: Melatonin significantly reduced the severity of NEC in our study. PMID- 22075340 TI - Predictors of postnatal outcome in neonates with gastroschisis. AB - BACKGROUND/PURPOSE: The optimal management of neonates with gastroschisis is unclear, and there is a significant morbidity. We performed a review of neonates with gastroschisis treated at our center of pediatric surgery over the last 21 years to determine predictive factors of outcome. METHODS: Single-center retrospective analysis of 79 neonates with gastroschisis (1989-2009) was done. Length of hospital stay (LOS), days of parenteral nutrition (PN), and survival were outcome measures. Univariate and multiple regression analyses were used. RESULTS: Overall survival was 92%, and primary closure was achieved in 80%. Median LOS was 25 days, and median duration on PN, 17 days. Intestinal atresia, closed gastroschisis, secondary closure, and sepsis were the primary variables associated with poor outcome independent of other variables, but prematurity also affected outcome. Route of delivery and associated malformations were not related to poorer outcome. Necrotizing enterocolitis did not occur in any of our patients. CONCLUSION: Outcome in our patients was favorable as measured by survival, LOS, and days on PN. Primary predictors of poor outcome were factors related to short bowel syndrome and secondary closure, indicating a need to further improve treatment of short bowel syndrome. PMID- 22075341 TI - Liver herniation in gastroschisis: incidence and prognosis. AB - PURPOSE: Liver herniation is a rare occurrence in gastroschisis. We sought to determine the incidence and prognosis of liver herniation in patients with gastroschisis. METHODS: From December 1995 to March 2010, 117 patients with gastroschisis received care by our division. Operative reports were reviewed to identify patients with liver herniation. Logistic regression was used to determine the impact of liver herniation on survival, taking into account gestational age and birth weight. RESULTS: The incidence of liver herniation was 6%. Survival rates were 43% with liver herniation and 97% without liver herniation. Liver herniation was associated with a significantly higher rate of mortality, taking into account estimated gestational age and birth weight (P < .001). Patients who had liver herniation documented by prenatal ultrasound had significant liver herniation at birth and died postnatally. Patients with liver herniation who died required large silos and were noted to have comorbidities including lower birth weight, pulmonary hypoplasia, and sepsis. Biologic patches were necessary for closure in patients with greater extent of liver herniation. CONCLUSIONS: Liver herniation was found in 6% of patients with gastroschisis and was associated with a high rate of mortality. Liver herniation appears to be a risk factor for poor outcome in gastroschisis. Documentation of liver herniation may be helpful in prenatal consultation for gastroschisis. PMID- 22075342 TI - The effect of surgical training and hospital characteristics on patient outcomes after pediatric surgery: a systematic review. AB - BACKGROUND/PURPOSE: A systematic review aimed to compare patient outcomes after (1) appendicectomy and (2) pyloromyotomy performed by different surgical specialties, surgeons with different annual volumes, and in different hospital types, to inform the debate surrounding children's surgery provision. METHODS: Embase, Medline, Cochrane Library, and Health Management Information Consortium were searched from January 1990 to February 2010 to identify relevant articles. Further literature was sought by contacting experts, citation searching, and hand searching appropriate journals. RESULTS: Seventeen relevant articles were identified. These showed that (1) rates of wrongly diagnosed appendicitis were higher among general surgeons, but there were little differences in other outcomes and (2) outcomes after pyloromyotomy were superior in patients treated by specialist surgeons. Surgical specialty was a better predictor of morbidity than hospital type, and surgeons with higher operative volumes had better results. CONCLUSIONS: Existing evidence is largely observational and potentially subject to selection bias, but general pediatric surgery outcomes were clearly dependent on operative volumes. Published evidence suggests that (1) pediatric appendicectomy should not be centralized because children can be managed effectively by general surgeons; (2) pyloromyotomy need not be centralized but should be carried out in children's units by appropriately trained surgeons who expect to see more than 4 cases per year. PMID- 22075343 TI - Effect of phototherapy on growth factor levels in neonatal rat skin. AB - AIM: Neonates undergoing surgery may receive phototherapy (PT) for the treatment of hyperbilirubinemia. Although the effects of PT on neonatal structures are well documented, the effect of PT on wound healing has not been previously evaluated. An experimental study was performed to evaluate the effect of PT on growth factor levels responsible for wound healing in neonatal rat skin. MATERIALS AND METHODS: Eighteen Wistar newborn rats (7 +/- 2 g) were included in the study. Rats were randomized into 3 groups: control (CG), PT, and sham (SG) (n = 6). Both groups had 1-cm median dorsal skin incision. In CG, 1 * 1 cm of dorsal skin was sampled including the incised skin. The PT group received 5 banks of blue light (wave density, 30-40 MUw/cm(2) per nanometer; exposure distance, 45 cm). Phototherapy was started 24 hours after birth and exposed during light period (mean duration, 21 hours to 15 minutes +/- 2 hour to 1.5 minutes). Sham group consisted of animals that received a bank of white light with same exposure distance and a total duration of 26 hours to 18 minutes +/- 3 hours to 9.1 minutes. After exposure, 1 * 1 cm dorsal skin samples were obtained from both PT and SG groups, including the median incision. The effect of PT was evaluated with the expressions of vascular endothelial growth factor (VEGF), its receptor (VEGF receptor), and transforming growth factor beta (TGF-beta) in endothelial vessels and fibroblasts of neonatal skin samples. RESULTS: There was no significant difference between groups in VEGF receptor and transforming growth factor beta expressions. The VEGF levels in endothelial vessels were significantly decreased in PT and SG when compared with CG (P < .05). CONCLUSION: Vascular endothelial growth factor is a mediator of angiogenesis and may decrease in neonatal rat skin after light exposure. It can be suggested that decreased levels of VEGF after PT application may alter angiogenesis and also may adversely affect the healing features of neonatal skin. PMID- 22075344 TI - The use of digital photos and video images taken by a parent in the diagnosis of anal swelling and anal protrusions in children with normal physical examination. AB - PURPOSE: The purpose of this study is to demonstrate that digital photos and video images taken by a parent can provide a definite diagnosis and makes some diagnostic procedures (eg, air contrast enema, sigmoidoscopy) unnecessary for anal swelling and anal protrusions in children with normal physical examination. METHODS: In a 41-month period (September 2007-January 2011), 23 parents brought their children to the clinic, stating that they saw a swelling in the anal region and/or that something protruded from the anus while their children were defecating. If the visual inspection of the anal region and digital rectal examination of the patients were normal, parents were asked to take photos or record videos when the lesion occurred to make a diagnosis and avoid the need for air contrast enema and/or sigmoidoscopy. The parents were also asked either to send these images to the surgeon via e-mail or bring an image or the camera to the surgeon's office. The patients age, sex, symptoms, medical history, results of their first physical examination, photos and video records, and the diagnosis and treatment were recorded. All of these information were retrospectively reviewed. RESULTS: The photos provided by 20 parents and the video records from 3 parents were assessed, and the diagnoses of all patients were confirmed. Of these 23 patients, a definitive diagnosis of rectal prolapse in 8, hemorrhoids in 10, rectal polyps in 3, and sentinel skin tag in 2 was made. In addition, the photographic and video evidence gave the clinicians an idea of the degree of rectal prolapse in patients for whom this was a problem. Three patients diagnosed with a rectal polyp underwent polyp excision. One patient with rectal prolapse who was unresponsive to medical treatment underwent laparoscopic posterior rectopexy, and all other patients received medical treatment. CONCLUSION: When a swelling or protruding anal lesion in a child is discovered by parents and visual inspection of the anal region and digital rectal examination is normal, parents should be encouraged to take photos or videos of the anal region before performing air contrast enema and/or sigmoidoscopy. These photos and videos can provide a definitive diagnosis and prevent unnecessary diagnostic procedures. PMID- 22075345 TI - Influence of anesthesia on the results of intraoperative diagnostic electromyostimulation in patients with anorectal malformation. AB - BACKGROUND AND PURPOSE: Stimulation electromyography (sEMG) is useful in identifying the sphincter muscle (M) in patients with anorectal malformations (ARMs). This study evaluates the effect of anesthetic agents and M relaxants on sEMG findings. MATERIALS AND METHODS: Seventeen infants (10 boys and 7 girls) with a mean age of 6.3 months and mean body weight of 6.7 kg were included in a prospective randomized study. Anesthesia was induced by sevoflurane and opioids, and an epidural catheter was inserted caudally. Stimulation electromyography of levator ani M using 14 mA current was used, and latency and amplitude of the evoked compound M action potential (CMAP) were recorded. Patients were randomized into 2 groups. Group A received a local anesthetic epidurally, and sEMG was performed. Administration of the M relaxant and measurement of M response followed. In group B drug administration, sEMG and response measurement were performed after administration of M relaxant. RESULTS: Baseline CMAP was recorded in all patients. Average latency was 4.1 milliseconds, and average amplitude was 0.43 mV. In group A, the average latency was 4.0 milliseconds, and average amplitude was 0.65 mV. After administration of the M relaxant, the CMAP disappeared. In group B, no CMAP was observed immediately after administration of the M relaxant. CONCLUSION: Administration of the inhalational anesthetic, opioids, and local anesthetic did not influence the M response of M fibers in the levator ani M on sEMG and enables its localization during ARM reconstruction. Nondepolarizing M relaxation completely abolished the response. If M relaxant is necessary, cisatracurium is used. The most suitable method of anesthesia for ARM surgery appears to be inhalational anesthesia supplemented by opioids and epidural analgesia. PMID- 22075346 TI - Parental attitudes regarding analgesic use for children: differences in ethnicity and language. AB - PURPOSE: The aim of this study was to identify the impact of ethnicity and language on parental attitudes regarding analgesic use to treat children's pain. METHODS: A total of 206 parents of children undergoing outpatient surgery were recruited to complete the Medication Attitudes Questionnaire, a measure of parental beliefs about using analgesic medications to treat children's pain. Parents were grouped into one of 3 categories according to ethnicity and primary language spoken: English-speaking white, English-speaking Hispanic, and Spanish speaking Hispanic. Group differences in pain medication attitudes were examined. RESULTS: After controlling for socioeconomic status, English-speaking Hispanic parents endorsed higher levels of misconceptions about pain medication use, including a tendency to avoid analgesic use for children, compared with English speaking white and Spanish-speaking Hispanic parents. CONCLUSIONS: This study highlights parental characteristics, including ethnicity and language, which may place children at higher risk for undertreatment of acute pain based on misconceptions about analgesic use for children. Specifically, English-speaking Hispanic parents may be most likely to undertreat children's pain at home. Future studies are needed to identify the most appropriate means of providing education to counter parental misconceptions and support optimal pain management of children's pain in the home setting. PMID- 22075347 TI - The use of laparoscopy in ventriculoperitoneal shunt revisions. AB - INTRODUCTION: Ventriculoperitoneal shunts (VPSs) are routinely placed in children with hydrocephalus. However, they often encounter problems, and revisions are frequent. We sought to evaluate our institutional experience with laparoscopic assisted VPS revisions. METHODS: With institutional review board approval, a retrospective chart review of 17 consecutive patients who underwent 19 laparoscopic-assisted VPS revisions was conducted. Data extracted included patient demographics, indications for laparoscopic-assisted revision, complications, and shunt outcomes. RESULTS: The median age at revision was 12 years (0.4-20 years). Ten children (58.8%) had 2 or more previous VPS revisions. Indications for laparoscopic revision included adhesive obstruction, broken shunt retrieval, cerebrospinal fluid pseudocyst, diagnostic laparoscopy, and conversion from ventriculoatrial shunt to VPS. Three patients required repeat VPS revision for distal shunt failure, whereas 2 patients required repeat VPS revision for proximal dysfunction. Failures occurred 5 to 258 days after laparoscopic-assisted revision. Median follow-up was 21 weeks (interquartile range, 6-57 weeks). No patients developed abdominal infections postoperatively. CONCLUSION: Laparoscopy is useful in select patients with distal VPS failure. Patients with multiple previous revisions, prior abdominal surgery, previous intraperitoneal infections, broken devices, or cerebrospinal fluid pseudocysts may benefit from this approach. Further prospective studies with long-term follow-up are needed to determine which patients benefit most from the laparoscopic-assisted approach. PMID- 22075348 TI - Fifty-three-year experience with pediatric umbilical hernia repairs. AB - PURPOSE: The aim of this study was to evaluate the long-term surgical and patient reported outcomes of pediatric umbilical hernia (UH) repairs. METHODS: A retrospective review of all children (<18 years old) who underwent UH repair at Mayo Clinic-Rochester in the last half century was done. Follow-up was obtained by mailed survey. RESULTS: From 1956 to 2009, 489 children (boys, 251; girls, 238) underwent a primary UH repair. The mean age was 3.9 years (range, 0.01-17.8 years). Complicated UHs that required emergent repair (n = 34, or 7%) included recurrent incarceration (22), enteric fistula (7), strangulation (4), and evisceration (1). Mean UH size was 1.3 cm (range, 0.2-7.0 cm), varying by operative indication (1.0 cm emergent vs 1.5 cm elective repairs, P = .008) and decade of repair (2.2 cm, 1950s-60s vs 1.3 cm, 1990s-2000s; P = .001). Postoperative morbidity (2%) consisted of superficial wound infection (7), hematoma (3), and seroma (1). With a 66% survey response rate and mean follow-up of 13.0 years (range, 0-53.8 years), 8 (2%) patients experienced a recurrence. Most patients reported satisfaction (90%) with the cosmetic appearance of their umbilicus and are pain free (96%). CONCLUSION: Pediatric UH repairs have low morbidity and recurrence rates. Most patients are satisfied and pain free. Importantly, complicated UHs were more likely to be associated with smaller defects; therefore, parental counseling for signs of incarceration is recommended even in small defects. PMID- 22075349 TI - Neonatal testicular torsion: a survey of current practice amongst paediatric surgeons and urologists in the United Kingdom and Ireland. AB - PURPOSE: Management of neonatal testicular torsion (NTT) is controversial, with varied opinion regarding the merit(s) and role of "emergent" testicular exploration and/or contralateral orchidopexy of the healthy testis. METHODS: A survey of consultant paediatric surgeons and urologists working in the United Kingdom and Ireland was conducted to ascertain views to guide best practice. RESULTS: A total of 148 questionnaires were mailed, of which 110 were returned (74% response rate). Of these, 60 (54.5%) surgeons considered NTT secondary to torsion of the spermatic cord and 8 (7.2%) thought primary vascular infarction of the testis responsible. Twelve (10.9%) use Doppler ultrasound to guide management and exclude tumour. Eighty-two surgeons (74.5%) explore the scrotum, and 59 (71.9%) perform ipsilateral orchidectomy and contralateral orchidopexy of the "healthy" testis. Few surgeons undertake emergent exploration. Only 11 (10%) surgeons have ever found a viable testis. Seven (6.4%) cases of synchronous NTT were reported. Twenty-four (21.8%) surgeons do not perform contralateral orchidopexy with concerns of damaging a healthy testis. Orchidopexy is favoured by 89 surgeons, with 46 (52%) using nonabsorbable suture fixation and 28 (31.4%) creating a sutureless extradartos pouch. In boys later found to have a "solitary scrotal testis" and a contralateral testicular remnant, 38 (36.5%) of 104 would always "pex" the testis to avert anorchia. CONCLUSIONS: Surgeons' opinions with NTT in the United Kingdom and Ireland remain diverse. Strong argument can be made for scrotal exploration with/without contralateral orchidopexy. Parents should be counselled on the merits of varied strategies to gain better understanding of the long-term outcomes for their male child. PMID- 22075350 TI - The incidence and surgical management of paratubal cysts in a pediatric and adolescent population. AB - PURPOSE: The aim of this study is to determine the incidence of paratubal cysts (PTCs) in a pediatric and adolescent population. METHODS: An institutional review board-approved retrospective chart review was performed between the years of 1998 and 2008 at a single children's hospital. Inclusion criteria were met if pathology reports demonstrated diagnosis of PTC, hydrosalpinx, or hydatid of morgagni. RESULTS: One hundred ten patients had confirmed diagnoses of hydatid of morgagni, hydrosalpinx, or PTC. The incidence of PTCs was 7.3%. Mean age of PTC diagnosis was 13.7 +/- 2.82 years, with 12.6% diagnosed premenarchal. Mean age menarche was 11.7 +/- 1.34 years among pubertal females. The age of menarche and diagnosis of PTC correlated (Pearson, 0.54) (P < .0001). There was a small correlation between body mass index and size of PTC (r = 0.36; P <= .001). CONCLUSION: The incidence of PTCs was 7.3% in this pediatric and adolescent population. In addition, this is the first study to confirm presence of PTCs in prepubertal females. Surgeon should be aware of these benign cysts because they are frequently a source of abdominal pain in young girls. As nonphysiologic cysts, these will not resolve spontaneously and may increase in size and/or be at risk for adnexal torsion. Ultimately, surgical management is required for definitive resolution. PMID- 22075351 TI - Paratubal cysts, obesity, and hyperandrogenism. AB - OBJECTIVE: The aim of this study was to determine if an association exists between adolescents with polycystic ovarian syndrome (PCOS) or hyperandrogenism (HA), obesity, and paratubal cysts (PTCs). DESIGN: An institutional review board approved retrospective chart review was performed between the years of 1998 and 2008 at a single children's hospital. Inclusion criteria were met if pathology reports demonstrated diagnosis of PTC. Age of menarche, body mass index, surgical procedure, and findings were correlated with the presence of HA. RESULTS: The incidence of PTCs was 7.3% among 1524 females presenting with adnexal masses. One hundred three patients had a confirmed pathology diagnosis of PTC and underwent surgery for suspected torsion or persistent adnexal mass on imaging studies. Forty-five percent of surgical cases had ovarian or adnexal torsion. Mean age of PTC diagnosis for the entire cohort was 13.7 +/- 2.82 years. Mean age of menarche was 11.7 +/- 1.34 years among pubertal females. Four patients were premenarchal at the time of PTC diagnosis. Forty percent of pubertal females had a diagnosis of PCOS. Pubertal adolescents with features of HA had a higher body mass index (31.3 vs 26.2 kg/m(2), P = .003) and had a trend toward larger cysts (7.6 vs 6 cm, P = .235). Overall, a significant association existed between obesity and PTC (P = .007), although no definite association could be made about HA or PCOS. CONCLUSION: This study demonstrated an association between PTCs and obesity. In addition, HA appears to be associated with a trend toward large PTCs, although results were not significant. PMID- 22075352 TI - Surgical management of facial nerve paralysis in the pediatric population. AB - BACKGROUND: In the pediatric patient population, both the pathology and the surgical managements of seventh cranial nerve palsy are complicated by the small size of the patients. Adding to the technical difficulty is the relative infrequency of the diagnosis, thus making it harder to become proficient in the management of the condition. The magnitude of the functional and aesthetic deficits these children manifest is significantly troubling to both the patient and the parents, which makes immediate attention, treatment, and functional restoration essential. METHODS: A literature search using PubMed (http://www.pubmed.org) was undertaken to identify the current state of surgical management of pediatric facial paralysis. RESULTS: Although a multitude of techniques have been used, the ideal reconstructive procedure that addresses all of the functional and cosmetic needs of these children has yet to be described. Certainly, future research and innovative thinking will yield progressively better techniques that may, one day, emulate the native facial musculature with remarkable precision. CONCLUSION: The necessity for surgical intervention in children with facial nerve paralysis differs depending on many factors including the acute/chronic nature of the defect as well as the extent of functional and cosmetic damage. In this article, we review the surgical procedures that have been used to treat pediatric facial nerve paralysis and provide therapeutic facial reanimation. PMID- 22075353 TI - Congenital-infantile fibrosarcoma masquerading as sacrococcygeal teratoma. AB - Infantile fibrosarcoma is rare and represents less than 1% of all childhood cancers. Commonly, it arises in the limbs followed by the trunk and head and neck. We report a rare case of infantile fibrosarcoma masquerading as sacrococcygeal teratoma in a newborn. The literature on the subject is also reviewed. PMID- 22075354 TI - The first male with thoracoschisis: case report and review of the literature. AB - A male infant presented at birth with intestine and liver herniated through a defect 3 cm below the left nipple on the anterior thoracic wall. Riedel lobe, attached to the left liver lobe, and the transverse colon were seen protruding through the defect at the region of the left eighth intercostal space at surgery. A fibrous band extending from the lower defect border to the bladder was present. The hernia content was reduced inside the abdomen and the fibrous band, and Riedel lobe and necrotic-appearing omentum were excised. Thoracoschisis is a very rare congenital anomaly with only 4 cases reported. This is the first isolated thoracoschisis case without an accompanying diaphragmatic hernia. PMID- 22075355 TI - Diagnosis and management of congenital rectourethral fistula in a child with long tubular duplication of the colon and Klippel-Feil syndrome. AB - We describe a unique association of congenital rectourethral fistula with long tubular duplication of the colon in a boy with Klippel-Feil syndrome and Sprengel deformity. He presented with a rectourethral fistula after surgical repair of a tubular duplication of the terminal ileum, colon, and proximal rectum. Preoperative identification of the fistula was challenging and was only achieved after cystoscopy with injection of methylene blue under pressure through Foley catheters placed into the anus and distal stoma of a colostomy. Surgical repair was performed through the posterior sagittal approach. The patient is doing well after 4 years of follow-up. PMID- 22075356 TI - Congenital ectopic fistula of a minor salivary gland. AB - A rare case of congenital salivary gland fistula is reported. A 3-year-old girl presented with clear discharge from a dimple on the left cheek. An ectopic salivary gland fistula was unexpectedly diagnosed during operation. This is the first case of congenital salivary fistula draining from a minor salivary gland to a cutaneous pit. We completely excised the lesion, and the patient remains complication free. PMID- 22075357 TI - Left pulmonary artery sling with right lung aplasia. AB - We report 2 cases of right pulmonary aplasia with left pulmonary artery sling responsible for severe respiratory symptoms. Repositioning of the left pulmonary artery without tracheal surgery was successful in both patients. The postoperative course was simple, and the outcome was favorable at last follow-up (after 2 years and 3 months, respectively). Computed tomography provided an accurate diagnostic evaluation that helped to choose the best surgical technique. PMID- 22075358 TI - Retrograde intrarenal surgery in infants and preschool-age children. AB - OBJECTIVES: The objectives of this study are to present our experience with retrograde intrarenal surgery for management of renal calculi in children less than 7 years old and to determine its safety and efficacy in this age group. METHODS: Patient demographics, stone location and size, use of ureteral access sheath, stone-free status, complication rates, and follow-up were evaluated. RESULTS: A total of 16 patients (9 boys and 7 girls; mean age, 4.2 years) underwent 17 procedures. The mean stone size was 11.5 mm (8-17 mm). Flexible ureteroscopy and laser lithotripsy were performed in all cases regardless of stone location. Dilation of the ureteral orifice was required in 5 cases (29.4%), and ureteral access sheaths were placed in 3 patients (17.6%). With a mean follow up of 10.3 months, 88% of the children were stone free. The success rate for stones less than 10 mm was 100% and 81.8% for stones 10 mm or more (P < .05). There were no major complications, but there was 1 case of perforation and extravasation at the ureterovesical junction after balloon dilation that was managed with stent placement. CONCLUSIONS: Retrograde intrarenal surgery is a safe and effective method for the treatment of intrarenal calculi, and it achieves reasonable results with minimal complications in children less than 7 years old. PMID- 22075359 TI - Single-port laparoscopic Heller myotomy and Dor fundoplication: initial experience with a new approach for the treatment of pediatric achalasia. AB - PURPOSE: The aim of this report was to evaluate the safety and feasibility of single-port laparoscopic Heller myotomy and Dor fundoplication (SPLHD) as treatment of pediatric esophageal achalasia. METHODS: A 9-year-old boy with a significant history of achalasia underwent SPLHD. The single-port was inserted using an umbilical incision. The falciform ligament and left liver lobe were raised using an elevating suture, providing good visualization of the operative field at the cardia. The Heller myotomy was planned to be 4 cm long, extending 1 cm onto the gastric wall. RESULTS: The SPLHD was successfully accomplished without the need for any skin incisions or additional ports. Oral intake was resumed on the first postoperative day, and the length of hospital stay was 8 days. The patient had complete resolution of dysphagia and regurgitation. No complications were noted, and the patient had an excellent cosmetic result. CONCLUSIONS: The SPLHD is a safe and feasible procedure for symptomatic pediatric achalasia when performed by a surgeon experienced in laparoscopic and esophageal surgery. PMID- 22075360 TI - Knowledge of ancient Hindu surgeons on Hirschsprung disease: evidence from Sushruta Samhita of circa 1200-600 BC. AB - BACKGROUND: Congenital megacolon is eponymously named after Harold Hirschsprung, who accurately described the clinical features in 1886. Recent research revealed that this condition is perhaps well known for centuries before him. AIM: This article is intended to examine if ancient Hindu surgeons knew about congenital megacolon. METHODS AND MATERIALS: Sushruta Samhita is an ancient tome of Ayurvedic surgery compiled by Sushruta (circa 1200-600 bc). Passages of interest were identified by browsing the authentic English translation of the compendium. Accuracy of translation was verified by comparing to the original Sanskrit verses with the help of a Sanskrit scholar. RESULTS: A condition called Baddha Gudodaram, described in the Samhita, closely resembles Hirschsprung disease. There are indications that ancient Indians even deciphered the etiology as defective vayu alias vata (nerves). Although the ailment was considered incurable, a palliative operation has been discussed. Descriptive details of the operation match with that of sigmoid colostomy. CONCLUSION: Evidence from Sushruta Samhita indicates that Hindu surgeons of prehistoric India probably had considerable knowledge about Hirschsprung disease. Further research, corroborating other sources of evidence, is required to confirm this claim. PMID- 22075361 TI - Brave new world or the unfortunate natural history of "lethal" disease: when to push the envelope? PMID- 22075362 TI - Costs of congenital diaphragmatic hernia repair in the United States extracorporeal membrane oxygenation foots the bill. PMID- 22075364 TI - Laparoscopic cystectomy for splenic hydatid cyst: a case report. AB - Even in countries where it is considered endemic, splenic hydatid cyst is a very rare disease in childhood. Partial or total splenectomy has generally been the treatment of choice for this condition. This is the first report of laparoscopic cystectomy as treatment of isolated splenic hydatid cyst in childhood. A 10-year old girl with isolated splenic hydatid cyst was successfully treated by laparoscopic cystectomy and splenic preservation. The authors have demonstrated that laparoscopic cystectomy for an isolated splenic hydatid cyst is technically feasible, safe, and is associated with a shorter hospital stay and good cosmetic appearance. PMID- 22075365 TI - Giant ureteral polyps causing proximal ureter obstruction: emphasis on the surgical method and ureteroscopy. AB - We describe here the case of a 13-year-old boy who had right flank pain for 3 months. An intravenous pyelogram showed filling defects in the right upper part of the ureter as well as hydronephrosis. Because the diseased part of the ureter was about 5 cm in length and we wished to avoid short ureter after surgery, we performed a minimal segmental resection of the ureter including the entire stalk. Perioperative ureteroscopic examination showed another polyp 3 cm below the primary polyp, which was also removed. End-to-end ureteral anastomosis was performed without mobilization of the kidney. Frozen and formal microscopic examination showed that these polyps were fibroepithelial. PMID- 22075366 TI - An alternative approach for management of the congenital giant inguinal hernia in neonates. AB - Whereas inguinal hernias are commonly encountered in the neonatal population, giant hernias containing the entire small bowel and with complete inguinal floor disruption are significantly less common. These cases present clinical and technical challenges with the obliteration of normal anatomy and an attenuation of the expected abdominal domain. There is a scant literature available describing these hernias or their management in neonates. In this case report, we describe a neonate who presented with a giant unilateral inguinal scrotal hernia complicated by in utero perforation. This was managed by open herniorrhaphy, orchidopexy, and diagnostic laparoscopy. PMID- 22075367 TI - Pneumatosis intestinalis after laparoscopic appendectomy: case report and review of the literature. AB - Pneumatosis intestinalis (PI) is the presence of intraluminal gas within the wall of the intestine. As a marker for bowel injury owing to mucosal injury, PI may herald a severe underlying disease process in patients without a significant medical history. In other cases, PI is a benign process, and expectant management is appropriate. Here, we present the first reported case of pneumatosis associated with postoperative abscess after appendectomy and its successful management. Then, we describe the pathophysiology of pneumatosis and review the literature regarding its origin and management. PMID- 22075368 TI - Application of high-dose rate (60)Co remote after-loading system for local recurrent neuroblastoma. AB - The local control of neuroblastoma is a very important treatment consideration. We describe a patient who received high-dose rate 60Co remote after loading system treatment for local control of recurrent neuroblastoma and discuss the efficacy of high-dose rate 60Co remote after loading system treatment. PMID- 22075369 TI - Isolated congenital megacystis without intestinal obstruction: a mild variant of chronic intestinal pseudoobstruction syndrome? AB - Megacystis is frequently involved with chronic intestinal pseudoobstruction syndrome; however, isolated megacystis without intestinal obstruction is extremely rare. We present the case of a female patient with isolated congenital megacystis without severe intestinal obstruction. In this case, barium enema did not reveal any significant findings; however, histologic evaluation of her rectum showed hypoganglionosis of the submucous and myenteric plexuses. These findings indicate that this case may be a mild variant of chronic intestinal pseudoobstruction syndrome. The presence of megacystis should alert the physician to the possibility of chronic intestinal pseudoobstruction syndrome. PMID- 22075370 TI - A case of undifferentiated embryonic liver sarcoma mimicking cystic hydatid disease in an endemic region of the world. AB - Undifferentiated embryonic liver sarcoma (UELS) is a rare highly malignant neoplasm that predominantly occurs in children between 5 and 10 years of age. The typical radiologic appearance on ultrasound and computed tomography of UELS shows a large septated mass having combined cystic and solid components. These radiographic features, however, are not specific to UELS and are shared by other more common and benign diseases of the liver. For example, cystic hydatid disease (CHD), caused by larvae of the Echinococcus tapeworm, is the most common indication for hepatic operations in children residing in endemic regions of the world. Undifferentiated embryonic liver sarcoma and CHD are 2 diseases that share overlapping presenting features of patient age, symptoms, and radiologic appearance. Surgeons who operate in Echinococcal endemic regions must be aware that not all hepatic cystic masses are necessarily CHD and may be other more rare malignant diseases such as UELS. PMID- 22075371 TI - Learning interspecific communicative responses in Pampas foxes (Lycalopex gymnocercus). AB - Domestic dogs show remarkable communicative abilities in their interaction with people. These skills maybe explained by the interaction between the domestication process and learning experiences during ontogeny. Studies carried out on other species of canids, which have not been domesticated are relevant to this topic. The purpose of this article is to study the effect of instrumental learning on captive Pampas foxes' (Lycalopex gymnocercus) communicative responses to humans. Seven foxes were tested in a conflict situation involving food within sight but out of their reach. In these situations dogs typically gaze at the human face to ask for food. In Study 1, there was an increase in gaze duration as a consequence of reinforcement and a decrease during extinction, when animals did not receive any more food. In Study 2, all of the four foxes tested successfully followed proximal pointing gesture to find hidden food. When a distal pointing cue was given, three out of four followed it in the first session and one in the second session. These results are consistent with those previously found in dogs, and suggest that learning experiences allow the development of communicative skills, even in not domesticated canid species. PMID- 22075372 TI - Bilateral effects of 6 weeks' unilateral acupuncture and electroacupuncture on ankle dorsiflexors muscle strength: a pilot study. AB - OBJECTIVES: To determine the effect of unilateral manual acupuncture at selected acupoints on ankle dorsiflexion strength of both limbs, and compare the effect with that of electroacupuncture at the same acupoints and sham points. DESIGN: Randomized controlled trial. SETTING: Rehabilitation laboratory of a university. PARTICIPANTS: Young men (N=43) were randomly allocated into 4 groups: control; manual acupuncture and electroacupuncture on 2 acupoints (ST-36 and ST-39); and electroacupuncture on 2 nonacupoints. These points were located on the tibialis anterior muscle. INTERVENTIONS: The participants in the experimental groups received 15 to 30 minutes of acupuncture or electroacupuncture on the right leg in each session, 3 sessions per week for 6 weeks. MAIN OUTCOME MEASURES: The maximal strength in isometric ankle dorsiflexion of both legs was assessed before and after the experimental period. RESULTS: Repeated-measures analysis of variance identified significant and similar strength gains (range, 35%-64% in the right leg and 32%-49% in the left leg; P<.01) in all acupuncture groups, but not in the control group (-2% to 2%, P>.05). CONCLUSIONS: Unilateral manual acupuncture and electroacupuncture at the acupoints can improve muscle strength in both limbs, and electroacupuncture at the nonacupoints as used in this study can also induce similar strength gains. PMID- 22075373 TI - Thermal stability of vitamin C: thermogravimetric analysis and use of total ion monitoring chromatograms. AB - The thermal decomposition kinetics and shelf life of vitamin C in nitrogen or air were studied by using thermogravimetric analysis (TGA) and evolved-gas analysis lithium-ion attachment mass spectrometry (EGA-Li+IAMS). Arrhenius parameters obtained via TGA were reported for thermal decomposition. For vitamin C in a nitrogen atmosphere, the activation energy (E(a)) was 25.1 kcal/mol and the pre exponential factor (A) was 2.5 * 1011 min-1. The kinetic parameters estimated via TGA agreed with values estimated from a pyrogram when the weight loss observed by TGA was shown to be due to gas evolution as a result of decomposition of the compound. Thermal stability was expressed by calculating the time for 10% of the vitamin C to decompose at 25 degrees C (t(90%,25 degrees C)). The t(90%,25 degrees C) for vitamin C obtained via TGA or EGA-Li+IAMS was higher in nitrogen (2.0 and 2.0 years, respectively) than in air (1.3 and 1.6 years, respectively). This indicates that the type of atmosphere influences vitamin C stability. PMID- 22075374 TI - Development and application of a validated gradient elution HPLC method for simultaneous determination of 5-fluorouracil and paclitaxel in dissolution samples of 5-fluorouracil/paclitaxel-co-eluting stents. AB - The combined use of 5-fluorouracil and paclitaxel is common in clinical trials. However, there are few methods for simultaneous determination of 5-fluorouracil and paclitaxel; most reported approaches can only quantitate either 5 fluorouracil or paclitaxel. This paper proposes a new gradient elution HPLC method for simultaneous determination of 5-fluorouracil and paclitaxel using a photodiode array detector, C18 column (250 mm * 4.6 mm, 5 MUm) with methanol and 0.5% H3PO4 aqueous solution as the mobile phase components. The injection volume was 50 MUl and the column temperature was maintained at 30 degrees C. The method was validated according to USP Category I requirements. The validation characteristics included system suitability, linearity, analytical range, LOD, LOQ, accuracy, precision, specificity, stability, ruggedness and robustness. The calibration curves exhibited linear concentration ranges of 0.2-40 MUg/ml for 5 fluorouracil and 1.5-150 MUg/ml for paclitaxel with correlation coefficients larger than 0.99990. The lower limits of quantitation were 2 ng/ml for 5 fluorouracil and 0.75 MUg/ml for paclitaxel, respectively. The intra and inter day precision and accuracy were found to be well within acceptable limits (i.e., 5%). The results demonstrate that this method is reliable, reproducible and suitable for simultaneous quantitation of the two drugs in the release media of 5 fluorouracil/paclitaxel-co-eluting stents. PMID- 22075375 TI - Therapeutic effect of Yunnan Baiyao on rheumatoid arthritis was partially due to regulating arachidonic acid metabolism in osteoblasts. AB - In order to explore the potential therapeutic effect of Yunnan Baiyao (YNB) on rheumatoid arthritis (RA), rat models were constructed and orally administrated with YNB or methotrexate (MTX) in parallel. Clinical physical, histological and biochemical parameters showed trivial therapeutic difference between YNB and MTX applications. Urine and serum metabonomics results indicated that many endogenous metabolites differentially changed among the rats receiving diverse therapeutic interventions. Among them, the fluctuation of arachidonic acid (AA) was thought to make sense. Thus, its relevant metabolites were subjected to quantitation by using osteoblasts treated by YNB in vitro. It was found that YNB extract of 20 MUg/mL could greatly activate the synthesis of intracellular prostaglandin E2 and thromboxane B2 in osteoblasts. Excretion of prostaglandin D2 could be suppressed but not the thromboxane B2. This study proved the efficacy of YNB on curing RA and its potential mechanism through modulating AA metabolism in osteoblasts to some extent. PMID- 22075376 TI - A validated Ultra High Pressure Liquid Chromatographic method for the characterisation of confiscated illegal slimming products containing anorexics. AB - A fully validated UHPLC-DAD method for the identification and quantification of pharmaceutical preparations, containing molecules frequently found in illegal slimming products (sibutramine, modafinil, ephedrine, nor-ephedrine, metformin, theophyllin, caffeine, diethylpropion and orlistat) was developed. The proposed method uses a Vision HT C18-B column (2 mm * 100 mm, 1.5 MUm) with a gradient using an ammonium acetate buffer pH 5.0 as aqueous phase and acetonitrile as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile). Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 3.0% and 1.5%, the beta-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 3% for all of the considered components. A UHPLC-DAD method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations and which can, if necessary, be coupled to a MS-detector for a more thorough characterisation. PMID- 22075377 TI - Relative roles of Neogene vicariance and Quaternary climate change on the historical diversification of bunchgrass lizards (Sceloporus scalaris group) in Mexico. AB - Neogene vicariance during the Miocene and Pliocene and Quaternary climate change have synergistically driven diversification in Mexican highland taxa. We investigated the impacts of these processes on genetic diversification in the widely distributed bunchgrass lizards in the Sceloporus scalaris group. We searched for correlations between timing in diversification and timing of (1) a period of marked volcanism across the Trans-Mexican Volcanic Belt in central Mexico 3-7.5million years ago (Ma) and (2) a transition to larger glacial interglacial cycles during the mid-Pleistocene. From our phylogenetic analyses of mitochondrial DNA we identified two major clades that contained 13 strongly supported lineages. One clade contained lineages from the two northern sierras of Mexico, and the other clade included lineages associated with the Trans-Mexican Volcanic Belt and Central Mexican Plateau. Results provided support for Neogene divergences within the S. scalaris group in response to uplift of the Trans Mexican Volcanic Belt, a pattern observed in several co-distributed taxa, and suggested that Quaternary climate change likely had little effect on diversification between lineages. Uplift of the Trans-Mexican Volcanic Belt during specific time periods appears to have strongly impacted diversification in Mexican highland taxa. PMID- 22075378 TI - Lipocalin 2 in cancer: when good immunity goes bad. AB - The innate immune molecule Lipocalin 2 (LCN2) was initially shown to combat bacterial infection by binding bacterial siderophores, hence impairing microbial iron sequestration. In recent years, it has become apparent that LCN2 is over expressed in cancers of diverse histological origin and that it facilitates tumorigenesis by promoting survival, growth, and metastasis. Herein, we discuss emerging evidence that substantiates two functional roles for LCN2 in cancer: promotion of the epithelial-to-mesenchymal transition (EMT) that facilitates an invasive phenotype and metastasis, and sequestration of iron that results in cell survival and tumorigenesis. Further, we present evidence that upregulated LCN2 expression in solid tumors is induced by hypoxia and pro-inflammation, microenvironmental noxae that converge to cause an endoplasmic reticulum (ER) stress response. Taken together, it appears that tumor cells exploit the beneficial innate immune function of LCN2 to support uncontrolled growth. This duplicity in function highlights LCN2 and its upstream driver, the ER stress response, as key targets for cancer therapy. PMID- 22075379 TI - Understanding the role of cytokines in Glioblastoma Multiforme pathogenesis. AB - Cytokines play a significant role in cancer diagnosis, prognosis and therapy. The immune system's failure to recognize the malignant tumor cells and mount an effective response may be the result of tumor-associated cytokine deregulation. Glioblastoma Multiforme (GBM) has a characteristic cytokine expression pattern, and abnormalities in cytokine expression have been implicated in gliomagenesis. Within the heterogeneous GBM microenvironment, the tumor cells, normal brain cells, immune cells, and stem cells interact with each other through the complex cytokine network. This review summarizes the current understanding of the functions of key cytokines on GBM, and highlights potential therapeutic applications targeting these cytokines. PMID- 22075380 TI - Synergistic antitumor effect of adenovirus-mediated hING4 gene therapy and (125)I radiation therapy on pancreatic cancer. AB - Pancreatic cancer has a poor prognosis, even with surgery. ING4 is a member of the inhibitor of growth (ING) tumor suppressor family that has potent inhibitory effects on a variety of tumors; meanwhile, radiotherapy is a common adjunctive therapy for pancreatic cancer. Prior to this study, the effectiveness of a combination of ING4 gene-therapy and radiotherapy against pancreatic cancer had been unknown. In this study, we demonstrated that either ING4 or (125)I radiotherapy treatment could induce Panc-1 pancreatic cancer cell growth suppression and apoptosis in vitro. Furthermore, both treatments inhibited tumor growth and angiogenesis of Panc-1 pancreatic cancer subcutaneously xenografted in vivo. Moreover, the combination therapy had a synergistic effect. PMID- 22075381 TI - Changes in actin and E-cadherin expression induced by 5-aminolevulinic acid photodynamic therapy in normal and Ras-transfected human mammary cell lines. AB - Photodynamic therapy (PDT) is an anticancer treatment based on light-induced destruction of photosensitised malignant cells. It has been reported that PDT strongly affects cell-cell and cell-substrate adhesion through the reorganization of some cytoskeletal and adhesion proteins. The aim of the present work was to study the changes induced by PDT employing aminolevulinic acid (ALA), on the cytoskeleton actin network and E-cadherin expression. We employed the normal mammary HB4a cell line and its tumor counterpart transfected with the oncogene H Ras, which has been shown to be resistant to PDT. Ras insertion induces per se disorganization of both F-actin and E-cadherin distribution. ALA-PDT induces on HB4a cells a dramatic disorganization of actin stress fibers, resembling normal Ras-transfected cells. After 48h some features of disorganization remain present. In HB4a-Ras cells, F-actin exhibits signals of photodamage, but distribution is recovered 24h after treatment. On the other hand, PDT did not impact on E cadherin distribution, other than a transient disorganization, which was recovered at 24h. Moreover, E-cadherin disorganization did not favoured cell-cell detachment after PDT of HB4a-Ras cells. Actin but not E-cadherin constitutes in this model an important target of PDT. The fact that some features of microfilament disorganization remain present in HB4a surviving cells but not in Ras-transfected cells, suggests that cytoskeletal structures such as F-actin may be involved in the mechanisms of resistance to PDT. PMID- 22075382 TI - Response of pigmented Serratia marcescens to the illumination. AB - Variations in the illumination conditions (light/darkness) affected both the biosynthesis of prodigiosin and energy metabolism of the pigmented strain ATCC 9986 Serratia marcescens growing aerobical in the batch culture were shown. In the process incubation the transition of the pigmented culture from illumination within (24 h, 48 h) in the dark conditions increased the prodigiosin synthesis by 2.0, 2.5 times, respectively. At the same time, the illumination did not influence the prodigiosin biosynthesis in the stationary growth phase. In the initial period of prodigiosin synthesis the rate of oxygen consumption was higher than later when the pigment synthesis gradually decreased. The respiration activity of colorless strain 24-5 is not independent from the lighting conditions. The regulation of energetic pathways in the light and in darkness has been revealed. Prodigiosin is associated with the hydrophobic protein and it is represented pigment protein complex by diameter of particles less 100 kDa. Fluorescence spectrum of prodigiosin and it the absorption spectra of derivatives of high orders D(IV) and D(VIII) were described. PMID- 22075383 TI - [A trick to improve the technique of the IntraVascular Stent (IVaS): "Clip Stent"]. AB - The infra-millimetre vessels are difficult to suture, because the placement of forceps in the lumen is delicate and threads often cross the walls. The technique of the IntraVascular Stent (IVaS), developed to remedy it, did not make the proof of its superiority. The purpose of this study was to analyze the results of a variant, the Clip Stent. Our series included two groups of 10 rats. In group I, the artery of the tail was anastomosed by threads of nylon 10/0. In group II, the artery was anastomosed according to the technique of Clip Stent including three stages: introduction of a monothread of polypropylene 6/0, anastomosis by threads of nylon 10/0, ablation of the Clip Stent and the closure of possible leaks. The assessment consisted in measuring the time of anastomosis, in counting the number of separate threads and leaks, and in testing the permeability. The time of anastomosis was longer 12 minutes in the group II. The number of points by anastomosis was 6.5 in the group I and of 5.5 in the group II. The permeability was 90% in two groups. The Clip Stent is faster than the IVaS. It is useless to realize vascular threads of the lumen before the introduction of the stent. Once the stent in position, it cannot traumatize the intima and its migration is impossible. Contrary to the IVaS, the Clip Stent allows to realize the last threads stent in position, by releasing the tourniquet. The ablation is safe. Its superiority to the conventional methods remains to demonstrate by improving its introduction in the lumen. PMID- 22075384 TI - Differential mTOR and ERK pathway utilization by effector CD4 T cells suggests combinatorial drug therapy of arthritis. AB - The signaling pathways utilized by naive and experienced effector CD4 T cells during activation and proliferation were evaluated. While inhibition of either mTOR or MAPK alone was able to inhibit naive T cell proliferation, both mTOR and MAPK (ERK) pathway inhibition was required to efficiently block experienced, effector CD4 T cell proliferation. This was demonstrated both in vitro, and in vivo by treating mice with collagen-induced arthritis using mTOR and/or ERK inhibitors. The combination of mTOR and ERK inhibition prevented or treated disease more efficiently than either agent alone. These data illustrate the different requirements of naive and experienced effector CD4 T cells in the use of the mTOR and MAPK pathways in proliferation, and suggest that therapies targeting both the mTOR and MAPK pathways may be more effective than targeting either pathway alone in the treatment of CD4 T cell-mediated autoimmunity. PMID- 22075385 TI - Uterine and ovarian carcinosarcomas overexpressing Trop-2 are sensitive to hRS7, a humanized anti-Trop-2 antibody. AB - BACKGROUND: We evaluated the expression of human trophoblastic cell-surface marker (Trop-2) and the potential of hRS7 - a humanized monoclonal anti-Trop-2 antibody - as a therapeutic strategy against treatment-refractory human uterine (UMMT) and ovarian (OMMT) carcinosarcoma cell lines. MATERIALS AND METHODS: Trop 2 expression was evaluated by immunohistochemistry (IHC) in paraffin-embedded tumor tissues, by real-time polymerase-chain-reaction (RT-PCR) and flow-cytometry in cell lines. Sensitivity to hRS7 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity was tested using 5-hour chromium release assays against UMMT and OMMT cells. RESULTS: Trop-2 expression was elevated in 9 of 26 (35%) UMMT and 8 of 14 (57%) OMMT tissues tested by IHC. Positivity for Trop-2 mRNA by RT-PCR and surface expression by flow cytometry were detected in 2 of 4 cell lines, with high positivity noted in OMMT-ARK-2. OMMT-ARK-2 was highly sensitive to hRS7 ADCC (range: 34.7-41.0%; P < 0.001) with negligible cytotoxicity seen in the absence of hRS7 or in the presence of control antibody (range: 1.1-2.5%). Human IgG did not significantly inhibit ADCC while human complement increased, hRS7-mediated-cytotoxicity against OMMT-ARK-2. CONCLUSION: Trop-2 is overexpressed in a proportion of UMMT and OMMT, and hRS7 may represent a novel, potentially highly effective treatment option for patients with treatment-refractory carcinosarcomas overexpressing Trop-2. PMID- 22075386 TI - Comments on "Hinfinity synchronization of uncertain fractional order chaotic systems: adaptive fuzzy approach" [ISA Trans 50 (2011) 548-556]. AB - In this note, we demonstrate that the stability analysis in the main theorem of the paper [Lin T-C, Kuo C-H. H(infinity) synchronization of uncertain fractional order chaotic systems: adaptive fuzzy approach. ISA Trans 2011;50:548-56] is wrong. PMID- 22075387 TI - A portable hardware-in-the-loop (HIL) device for automotive diagnostic control systems. AB - In-vehicle driving tests for evaluating the performance and diagnostic functionalities of engine control systems are often time consuming, expensive, and not reproducible. Using a hardware-in-the-loop (HIL) simulation approach, new control strategies and diagnostic functions on a controller area network (CAN) line can be easily tested in real time, in order to reduce the effort and the cost of the testing phase. Nowadays, spark ignition engines are controlled by an electronic control unit (ECU) with a large number of embedded sensors and actuators. In order to meet the rising demand of lower emissions and fuel consumption, an increasing number of control functions are added into such a unit. This work aims at presenting a portable electronic environment system, suited for HIL simulations, in order to test the engine control software and the diagnostic functionality on a CAN line, respectively, through non-regression and diagnostic tests. The performances of the proposed electronic device, called a micro hardware-in-the-loop system, are presented through the testing of the engine management system software of a 1.6 l Fiat gasoline engine with variable valve actuation for the ECU development version. PMID- 22075388 TI - The ameliorating effect of dantrolene on the morphology of urinary bladder in spinal cord injured rats. AB - In animal models of spinal cord injury (SCI), the urinary bladder can undergo significant structural and physiological alterations. Dantrolene has been shown to be neuroprotective by reducing neuronal apoptosis after SCI. Furthermore, in addition to its anti-inflammatory and antioxidant properties, it appears to have a beneficial action on voiding, once this drug acts on the external urethral sphincter relaxation. In the present study, we investigated the effects of dantrolene on urinary bladder injury that follows experimental SCI. Forty-six male Wistar rats were laminectomized at T13, and a compressive trauma was performed to induce SCI. After euthanasia, the urinary bladder was removed for gross and histological evaluation. Traumatized animals showed urinary retention with severe hemorrhagic cystitis. Injured animals treated with dantrolene had less bladder hemorrhage and inflammatory infiltrate than those treated with placebo (p<0.05). Our results demonstrate that dantrolene may protect against urinary bladder lesions that follow SCI. Treating spinal cord-injured patients with this agent may be a promising additional therapeutic strategy to alleviate the accompanying inflammatory process. The results of the current study show that dantrolene has protective effects on spinal cord contusion-induced urinary bladder injury. The impaired integrity of bladder morphology was ameliorated by dantrolene treatment. PMID- 22075389 TI - Heterologous expression and characterization of a sigma glutathione S-transferase involved in carbaryl detoxification from oriental migratory locust, Locusta migratoria manilensis (Meyen). AB - Glutathione S-transferases (GSTs) play a major role in detoxification of xenobiotics and resistance to insecticides in insects. In the present study, a sigma-class GST gene (LmGSTs3) was identified from the locust, Locusta migratoria manilensis. Its full-length cDNA sequence is 828 bp containing an open reading frame (ORF) of 612 bp that encodes 204 amino acid residues. The predicted protein molecular mass and pI are 23.4 kDa and 7.62, respectively. Recombinant LmGSTs3 was heterologously expressed in Escherichia coli as a soluble fusion protein. Its optimal activity was observed at pH 8.0. Incubation for 30 min at temperatures below 40 degrees C scarcely affected activity. The LmGSTs3 at pH values between 4.0 and 11.0 retained more than 80% of its original activity. Ethacrynic acid and cibacron blue were very effective inhibitors of LmGSTs3 with I50-values 1.7 and 3.7 MUM, respectively. In response to heavy metal (CuSO4, CdCl2) exposure there was a concentration-dependent and time-dependent decrease in activity. The nymph mortalities after carbaryl treatment increased 38.7% after LmGSTs3 were silenced. These results suggest that LmGSTs3 may be involved in carbaryl detoxification in L. migratoria manilensis. PMID- 22075390 TI - Re-examination of the roles of environmental factors in the control of body-color polyphenism in solitarious nymphs of the desert locust Schistocerca gregaria with special reference to substrate color and humidity. AB - This study re-examines the effects of environmental factors including substrate color, humidity, food quality, light intensity and temperature on the green-brown polyphenism, black patterning and background body color of solitarious (isolated reared) nymphs of Schistocerca gregaria. All individuals reared in yellow-green or yellow containers became green morphs, whereas those reared in white, ivory colored, blue, grey, brown, zinc-colored and black containers produced brown morphs in similar proportions. The intensity of black patterns was negatively correlated with the brightness of the substrate color of the containers. Humidity, which previous studies claimed controls green-brown polyphenism in this species, exerted no significant influence on either the green-brown polyphenism or the black patterning. Food quality also had little effect on body color. High temperature tended to inhibit darkening. The background body color on the thorax was greatly influenced by the substrate color of rearing containers and a close correlation was found between these two variables, indicating that, in contrast to what has been suggested by others, this species exhibits homochromy to match the body color to the substrate color of its habitat. Similar responses were observed in another strain, although some quantitative differences occurred between the two strains examined. Based on these results, a new model explaining the control of body-color polyphenism in this locust is proposed and the ecological significance of black patterns in solitarious nymphs is discussed. PMID- 22075391 TI - Ethical considerations associated with clinical use of next-generation sequencing in children. PMID- 22075400 TI - Comparative analyses of the complete mitochondrial genomes of Ascaris lumbricoides and Ascaris suum from humans and pigs. AB - Ascaris lumbricoides and Ascaris suum are parasitic nematodes living in the small intestine of humans and pigs, and can cause the disease ascariasis. For long, there has been controversy as to whether the two ascaridoid taxa represent the same species due to their significant resemblances in morphology. However, the complete mitochondrial (mt) genome data have been lacking for A. lumbricoides in spite of human and animal health significance and socio-economic impact globally of these parasites. In the present study, we sequenced the complete mt genomes of A. lumbricoides and A. suum (China isolate), which was 14,303 bp and 14,311 bp in size, respectively. The identity of the mt genomes was 98.1% between A. lumbricoides and A. suum (China isolate), and 98.5% between A. suum (China isolate) and A. suum (USA isolate). Both genomes are circular, and consist of 36 genes, including 12 genes for proteins, 2 genes for rRNA and 22 genes for tRNA, which are consistent with that of all other species of ascaridoid studied to date. All genes are transcribed in the same direction and have a nucleotide composition high in A and T (71.7% for A. lumbricoides and 71.8% for A. suum). The AT bias had a significant effect on both the codon usage pattern and amino acid composition of proteins. Phylogenetic analyses of A. lumbricoides and A. suum using concatenated amino acid sequences of 12 protein-coding genes, with three different computational algorithms (Bayesian analysis, maximum likelihood and maximum parsimony) all clustered in a clade with high statistical support, indicating that A. lumbricoides and A. suum was very closely related. These mt genome data and the results provide some additional genetic evidence that A. lumbricoides and A. suum may represent the same species. The mt genome data presented in this study are also useful novel markers for studying the molecular epidemiology and population genetics of Ascaris. PMID- 22075401 TI - Neurohormonal and cytokine fluctuations following transcatheter closure for an atrial septal defect. AB - INTRODUCTION: Inflammation and neurohormonal activation are considered to be involved in the development of earlier and/or later complications in congenital heart disease patients, even after a successful repair of the lesion. It is not yet clarified what is the role of the therapeutic interventions in the occurrence of such a response and how it could be associated with possible postoperative complications. AIM: We sought to assess the inflammatory and neurohormonal response to transcatheter closure of secundum type atrial septal defects (ASD) over a six-month follow-up period. We also evaluated the association between the respective markers and catheterization data as well as echocardiographic measurements. METHODS: Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), N-terminal-proatrial natriuretic peptide (NT-proANP) and N-terminal-probrain natriuretic peptide (NT proBNP) were assessed and echocardiographic measurements were performed in twenty eight patients with atrial septal defect prior to, and at the first, second and sixth months post transcatheter closure. Thirty-three age-matched healthy volunteers were also enrolled. RESULTS: IL-6 plasma levels, although higher preoperatively, [physical logarithm (ln) IL-6: 3.37+/-0.66 vs 2.92+/-0.44 pg/ml, p=0.015], reached control levels postoperatively, at the end of the third month, whereas TNF-alpha and IL-10 were not influenced by the procedure. NT-proANP levels were elevated preoperatively compared to the control group (ln NT-proANP 3.78+/-0.572 vs 3.48+/-0.30, p=0.031), with a further significant increase during the 1st month (ln NT-proANP 3.78+/-0.572 vs 4.2+/-0.42, p=0.006), following the pattern of the left atrial volume enlargement, and remained high even 6 months after the procedure .On the other hand, the initially normal concentrations of NT proBNP, after a transient significant increase during the first month postoperatively (ln NT-proBNP 3.56+/-0.94 vs 4.58+/-0.91, p<0.0001) returned to the controls' levels at the end of the third month. Preoperative concentrations of NT-proANP positively correlated with NT-proBNP concentrations and pulmonary to systemic flow ratio (Qp/Qs). CONCLUSIONS: Transcatheter closure could improve, on a mid- term basis, the inflammatory process but natriuretic peptides' secretion continues in parallel with left atrial volume increase. Further follow up is required to determine the long-term progress of the inflammatory and neurohormonal response to the procedure. PMID- 22075402 TI - [Scientific studies are required to validate the indications for long-term oxygen therapy at high altitudes]. PMID- 22075403 TI - Two types of presentation of pulmonary inflammatory pseudotumors. AB - Inflammatory pseudotumors are a relatively uncommon pathology of uncertain etiology, generally considered to be reactive in origin. They may be observed in different locations as single or multiple masses. One of the possible forms of presentation is intrapulmonary. Despite its low frequency, this pathology should be considered in the differential diagnosis of lung nodules, even though the histologic results and the imaging tests can become confusing. In addition, pulmonary inflammatory pseudotumors present a low malignancy with good response to surgical treatment as well as to pharmacological therapy, although to a lesser degree. We present a bibliographic review of this pathology based on two cases observed in our hospital. Both patients debuted with non-specific respiratory symptoms and lung nodules on imaging studies that were suspicious for neoplastic processes. After an exhaustive study, the diagnosis of pulmonary inflammatory pseudotumor was reached, with excellent responses to the treatment used in each case. PMID- 22075404 TI - Lung affectation in an adult patient with Niemann-Pick disease, type B. AB - We have carried out a review of the literature after the presentation of a case of Niemann-Pick (N-P) disease type B reporting the radiological findings with special emphasis on lung affectation. The patient is 40 years old and was diagnosed at the age of 6 with possible N-P disease suspected due to the presentation of hepatosplenomegaly and reticular pattern on chest radiography, with initially normal lung function tests. Said diagnosis was confirmed by measuring the activity of acid sphingomyelinase (ASM) enzyme in skin fibroblast cultures and by demonstrating the presence of mutations in the ASM gene. In cases of storage disease, lung affectation should always be considered, and the most reliable radiological technique is high-resolution computed tomography. Although the "crazy-paving" pattern is not the most specific for this pathology, N-P disease should be included in the differential diagnosis. PMID- 22075406 TI - Pulmonary edema following scorpion envenomation: mechanisms, clinical manifestations, diagnosis and treatment. AB - Scorpion envenomation is common in tropical and subtropical regions. Cardio respiratory manifestations, mainly cardiogenic shock and pulmonary edema, are the leading causes of death after scorpion envenomation. The mechanism of pulmonary edema remains unclear and contradictory conclusions were published. However, most publications confirm that pulmonary edema has been attributed to acute left ventricular failure. Cardiac failure can result from massive release of catecholamines, myocardial damage induced by the venom or myocardial ischemia. Factors usually associated with the diagnosis of pulmonary edema were young age, tachypnea, agitation, sweating, or the presence of high plasma protein concentrations. Treatment of scorpion envenomation has two components: antivenom administration and supportive care. The latter mainly targets hemodynamic impairment and cardiogenic pulmonary edema. In Latin America, and India, the use of Prazosin is recommended for treatment of pulmonary edema because pulmonary edema is associated with arterial hypertension. However, in North Africa, scorpion leads to cardiac failure with systolic dysfunction with normal vascular resistance and dobutamine was recommended. Dobutamine infusion should be used as soon as we have enough evidence suggesting the presence of pulmonary edema, since it has been demonstrated that scorpion envenomation can result in pulmonary edema secondary to acute left ventricular failure. In severe cases, mechanical ventilation can be required. PMID- 22075407 TI - Myocardial infarction-stroke association. PMID- 22075408 TI - Differential impact of cytochrome 2C9 allelic variants on clopidogrel-mediated platelet inhibition determined by five different platelet function tests. AB - BACKGROUND: The antiplatelet effect of clopidogrel is subject to considerable inter-individual variations. In vitro high on-treatment residual platelet reactivity (HRPR) has been linked to cytochrome P450 (CYP) 2C19*2 carriage, and both were significantly associated with the occurrence of adverse events after coronary stenting. It has been shown that besides CYP2C19, CYP2C9 is involved in the hepatic biotransformation of clopidogrel to its active metabolite. Consequently, CYP2C9 polymorphisms may also affect the extent of clopidogrel mediated platelet inhibition. We therefore studied the influence of CYP2C9 allelic variants on clopidogrel-mediated platelet inhibition as assessed by 5 platelet function tests. METHODS: On-clopidogrel residual platelet reactivity was assessed by light transmission aggregometry (LTA), the VerifyNow P2Y12 assay, the VASP assay, multiple electrode aggregometry (MEA), and the Impact-R in 288 patients after angioplasty and stenting for cardiovascular disease. Allelic variants CYP2C9*2 and *3 were determined using a RealTime PCR assay. RESULTS: A significantly higher on-treatment platelet reactivity was found for patients with loss-of-function (LOF) status (wt/*3, *2/*2, *3/*3) compared to normal-function genotype (wt/wt, wt/*2) using the VerifyNow assay (P=0.01). An in trend increase was seen with LTA (P=0.06) while results did not differ for the VASP assay, MEA or the Impact-R. Further, in univariate and multivariable logistic regression analysis the LOF genotype was associated with HRPR determined by the VerifyNow P2Y12 assay (P=0.02) but not by any other assay. CONCLUSION: Results from the VerifyNow P2Y12 assay are significantly influenced by CYP2C9 LOF variants leading to decreased clopidogrel-mediated platelet inhibition and an increased rate of HRPR. PMID- 22075409 TI - Hydatid cyst of the cardiac interventricular septum. PMID- 22075410 TI - Six-month follow-up evaluation for everolimus-eluting stents by intracoronary optical coherence tomography: comparison with paclitaxel-eluting stents. AB - BACKGROUND: Although several clinical trials have shown the superior efficacy and safety of second-generation everolimus-eluting stents (EES) in comparison with first-generation paclitaxel-eluting stents (PES), the differences in the vascular healing process between EES and PES in a human coronary artery during an early stage are unknown. METHODS: A prospective optical coherence tomography (OCT) observation was performed for 25 EES in 21 patients and 27 PES in 21 patients at 6 months after implantation. Cross-sections within single-stent segments were analyzed at intervals of 1mm. The neointimal (NI) thickness on each strut was measured. Uncovered struts (NI thickness=0 MUm), malapposed struts, NI area (%), uncovered strut ratio >0.3 (UCSR; number of uncovered struts/number of total struts) per cross-section, and in-stent thrombus were evaluated. RESULTS: A total of 5198 EES struts in 514 cross-sections and 4243 PES struts in 469 cross sections were identified. NI thickness and its area were smaller for EES than PES (80.0 +/- 84.8 MUm vs. 117.9 +/- 140.0 MUm and 19.1 +/- 8.9% vs. 23.7 +/- 11.5%, respectively; P<0.001). The frequencies of uncovered struts and malapposed struts were lower in EES compared to PES (2.3% vs. 5.2% and 2.1% vs. 5.7%, respectively; P<0.001). Patients who had cross-sections of UCSR >0.3 and thrombi were identified less frequently in EES than in PES group (5% vs. 57%; P<0.001, and 19% vs. 48%; P=0.05, respectively). CONCLUSIONS: Six-month OCT examination showed a favorable vessel healing response after the implantation of EES, demonstrating less in-stent late loss as well as fewer uncovered struts and better stent apposition to the vessel wall in comparison with PES. PMID- 22075411 TI - Freedom poverty: a new tool to identify the multiple disadvantages affecting those with CVD. AB - BACKGROUND: It is recognised that CVD affects an individual's financial situation, placing them in income poverty. However, recent developments in poverty measurement practice recognises other forms of disadvantage other than low income, such as poor health and insufficient education also affect living standards. METHODS: Using the Freedom Poverty Measure, the multiple forms of disadvantage experienced by those with no health condition, heart disease, other diseases of the circulatory system, and all other health conditions was assessed using data on the adult Australian population contained in the 2003 Survey of Disability, Ageing and Carers. RESULTS: 24% of those with heart disease and 23% of those with other diseases of the circulatory system were in freedom poverty, suffering from multiple forms of disadvantage. Those with heart disease and those with other diseases of the circulatory system were around three times more likely to be in freedom poverty (OR 3.02, 95% CI: 2.29-3.99, p<.0001; OR 2.78, 95% CI: 1.94-3.98, p<.0001) than those with no health condition. CONCLUSIONS: Recognising the multiple forms of disadvantage suffered by those with CVD provides a clearer picture of their living standards than just looking at their income alone and the high proportion of individuals with CVD that are suffering from multiple forms of disadvantage should make them a target for policy makers wishing to improve living standards. PMID- 22075412 TI - A randomized comparison of sirolimus- vs. paclitaxel-eluting stents for treatment of bifurcation lesions by single stent and kissing balloon: results of the SINGLE KISS trial. AB - BACKGROUND: In the treatment of bifurcation lesions, routine stenting of both branches has thus far failed to demonstrate a clear clinical advantage over a provisional one-stent strategy. On the other hand, large scale data evaluating different stent types for clinical outcomes after one-stent treatment with final kissing inflation (FKI) of bifurcation lesions is also limited. This prospective study evaluated the clinical and angiographic outcomes of paclitaxel-eluting stents (PES) vs. sirolimus-eluting stents (SES) in single crossover main branch stenting followed by FKI in patients with bifurcation lesions. METHODS: We randomized 800 patients with single bifurcation lesions to PES (n=400) and SES (n=400) groups. RESULTS: Crossover rates to the two-stent strategy were low in both groups (PES 1.5%, SES 2.8%; p=0.23). At 1 year, there was no significant difference in the primary endpoint of this study, target lesion revascularization rate (PES 3.8%, SES 3.2%, hazard ratio 0.83; 95% confidence interval 0.39 to 1.76; p=0.62). Stent thrombosis occurred in only 1 case in the SES group after 282 days. At 9 months, a total of 593 patients underwent quantitative coronary measurement. The main branch restenosis rate in the PES group was significantly higher than that of the SES group (PES 12.2%, SES 5.5%; p=0.004), however both groups exhibited similar high side branch restenosis rates (PES 17.2%, SES 19.3%; p=0.6). CONCLUSIONS: In patients with bifurcation lesions, a single stent strategy using PES and SES with FKI indicated similar 1 year clinical outcomes and safety profiles. PMID- 22075413 TI - Variability and treatment of high on-prasugrel platelet reactivity in patients with initial high on-clopidogrel platelet reactivity. PMID- 22075414 TI - Doppler peak-plateau morphology in pulmonary regurgitation flow with respiratory changes of its profile revealing hemodynamic features of restrictive cardiomyopathy. PMID- 22075415 TI - Unraveling the EXCEL: promises and challenges of the next trial of left main percutaneous coronary intervention. AB - The Evaluation of Xience Prime or Xience V versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is a multicenter, ongoing trial conducted in patients with left main disease and SYNTAX score <= 32 to establish the presumptive advantage of percutaneous coronary intervention (PCI) versus bypass surgery in patients with less complex coronary artery disease than those enrolled in the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial. In this article, we aimed at critically discussing key features and issues relevant to design and clinical interpretation of this new contemporary trial of left main PCI. PMID- 22075416 TI - Congenital absence of the right coronary artery with superdominant left circumflex coronary artery. PMID- 22075417 TI - Does mindfulness meditation shift the cardiac autonomic nervous system to a highly orderly operational state? PMID- 22075418 TI - Impact of diabetes mellitus on plaque vulnerability and clinical outcome in patients with acute myocardial infarction with plaque rupture. PMID- 22075419 TI - N-Terminal-proBrain natriuretic peptide measurement at presentation to identify patients with recent onset of atrial fibrillation. PMID- 22075420 TI - Persistent coronary arterial inflammation in a patient long after the onset of Kawasaki disease. PMID- 22075421 TI - Hypertensive crisis: comparison between diabetics and non-diabetics. PMID- 22075422 TI - Biomechanical analysis of the influence of friction in jaw joint disorders. AB - OBJECTIVE: Increased friction due to impaired lubrication in the jaw joint has been considered as one of the possible causes for internal joint disorders. A very common internal disorder in the jaw joint is an anteriorly dislocated articular disc. This is generally considered to contribute to the onset of arthritic injuries. Increase of friction as caused by impairment of lubrication is suspected to be a possible cause for such a disorder. METHOD: The influence of friction was addressed by analysis of its effects on tensions and deformations of the cartilaginous structures in the jaw joint using computational biomechanical analysis. Jaw open-close movements were simulated while in one or two compartments of the right joint friction was applied in the articular contact. The left joint was treated as the healthy control. RESULTS: The simulations predicted that friction primarily causes increased shear stress in the articular cartilage layers, but hardly in the articular disc. CONCLUSIONS: This suggests that impaired lubrication may facilitate deterioration of the cartilage subchondral bone unit of the articular surfaces. The results further suggest that increased friction is not a plausible cause for turning a normally functioning articular disc into an anteriorly dislocated one. PMID- 22075423 TI - Boring algae. PMID- 22075424 TI - Copper: an essential metal in biology. PMID- 22075425 TI - Changing expectations about speed alters perceived motion direction. PMID- 22075426 TI - Animal behavior: stay close for comfort. AB - Mate guarding - a male staying near a female for a while after mating - has traditionally been interpreted in the context of sexual conflict. New observations of wild field crickets suggest instead that guarding males provide protection from predators, enhancing female fitness. PMID- 22075427 TI - Neuroscience: how is three-dimensional space encoded in the brain? AB - A recent study in the rat has shown that hippocampal place cells and entorhinal grid cells exhibit vertically-elongated firing fields, indicating that the rat's brain may encode the animal's elevation less accurately than its horizontal position. PMID- 22075428 TI - Face recognition: vision and emotions beyond the bubble. AB - A new study of how neurons in the human amygdala represent faces and their component features argues for a holistic representation. PMID- 22075430 TI - Neurostimulation: a new way to influence cortical excitability? AB - Recent work in humans suggests that strong static magnets can modulate cortical excitability for a limited period of time. Can this provide an alternative to current neurostimulation approaches? PMID- 22075429 TI - Cell-cell junctions: alpha-catenin and E-cadherin help fence in Yap1. AB - Metazoan cells translate adhesive events with neighbors into anti-proliferative signals in the nucleus. The cadherin-catenin adhesion complex has long been suspected of playing a key role in this process, and three recent papers suggest that it does so by modulating subcellular localization of the Hippo pathway component Yap1. PMID- 22075431 TI - Circadian pacemakers: how clock properties relate to their cellular properties. AB - Circadian (~24 hour) pacemaking mechanisms exist within single cells. Which cellular properties contrive to produce a precise clockworks, and which cell properties are downstream of it? The literature is conflicted as to whether membrane excitability contributes to the mechanism. Now, a new conditional genetic strategy argues excitability is largely dispensable. PMID- 22075432 TI - Fungal sex: meiosis machinery in ancient symbiotic fungi. AB - Arbuscular mycorrhizal fungi are important symbionts that enhance plant growth. They were thought to have been asexual for hundreds of millions of years. A new study reveals that the fungi actually possess highly conserved genetic machinery for completion of meiosis. PMID- 22075434 TI - Trans-areola single-site endoscopic parathyroidectomy: report of one case. AB - This study presents a case report of parathyroid adenoma, which was managed by trans-areola single-site endoscopic parathyroidectomy. Two incisions were made along the right areola margin. The single subcutaneous narrow tunnel from the areola to neck was bluntly dissected in the right anterior chest. The authors successfully removed the adenoma through this channel. The intraoperative quick parathyroid hormone was decreased to a great extent. The operative time for the whole procedure was 110 minutes. The patient experienced transient postoperative hypocalcemia without recurrent laryngeal nerve palsy. She was very satisfied with the cosmetic results. PMID- 22075433 TI - Spindle checkpoint silencing: PP1 tips the balance. AB - The spindle checkpoint is a mitotic surveillance mechanism that delays anaphase until all sister chromatids are correctly attached to microtubules from opposite poles. Recent studies reveal that protein kinase Aurora B is a key regulator of spindle checkpoint activation whereas protein phosphatase PP1 antagonizes Aurora B and induces checkpoint silencing. Chromosome biorientation stretches the kinetochores and spatially separates centromeric Aurora B from its kinetochore substrates, comprising several PP1-interacting proteins (PIPs). The ensuing dephosphorylation of these PIPs creates docking sites for the bulk recruitment of PP1 to the kinetochores. We propose that this tension-induced targeting of PP1 triggers checkpoint silencing by the dephosphorylation of kinetochore and checkpoint components, including Aurora B substrates. In addition, PP1 also directly inactivates a kinetochore-associated pool of Aurora B and silences checkpoint signaling by opposing the centromeric targeting of Aurora B. PMID- 22075435 TI - From conception to application of a tele-operated assistance robot for middle ear surgery. AB - The authors' goal was to design and evaluate a robot dedicated to middle ear surgery. Specifications for dimensions, forces, and kinematics were collected, based on the otosclerosis procedure. The robot structure has a compact geometry with 3 linear and 3 rotatory motors. It is remotely piloted via a robot-surgeon interface under operative microscope. Ability to reach anatomical targets, to perform stapedectomy, and to place prosthesis in a model of stapedotomy was evaluated by 6 surgeons. Multiple anatomical targets in the middle ear could be successfully reached without damaging surrounding structures. The robot could be used under operative microscope with minimal visual field impairment or jointly with a 4-mm endoscope through the external auditory canal to perform stapedectomy in temporal bone specimens. Prosthesis could be inserted in the stapedotomy model. The assistance robot is the first prototype with 6 degrees of freedom, a kinematic structure, and dimensions optimized for tele-operated middle ear surgery. PMID- 22075436 TI - A noncontact laser-guided system for endoscopic computer-assisted sinus surgery. AB - The limited size of the nose leads to frequent instrument changes in navigated endonasal sinus surgery. Tracked instruments provide limited accuracy, and the pointer gives no navigation information during tissue removal. To overcome information loss, laser triangulation was integrated into navigation information. Accuracy and reliability of the laser-assisted distance-measuring system were evaluated within the distance of 0 and 20 mm. System accuracy of the laser endoscope was compared with a standard pointer using registration via bone screws and surface matching. Accuracy of the laser was 0.12 mm +/- 0.12 mm with a reliability of 0.2 mm. The system accuracy of the laser endoscope was 0.59 mm +/- 0.16 mm using bone screw registration and 0.64 mm +/- 0.22 mm using surface matching. Additionally, laser endoscope is more accurate compared with the pointer using bone screw registration. Overall, navigation information was successfully integrated into an endoscope by laser triangulation with encouraging results. PMID- 22075437 TI - Surface deformation analysis of end-to-end stapled intestinal anastomosis. AB - BACKGROUND: Stapling devices for creating anastomosis in internal organs are commonly used during surgery. Despite the obvious advantages of shortened procedure duration and fewer complications to manual suturing, staple-line leakage during intestinal anastomosis likely relates to the interaction between the staples and the tissue and to the tissue mechanical properties. The authors studied the deformation pattern close to the anastomosis to learn more about the mechanism involved in leakage. METHODS: End-to-end anastomosis in pig small intestine was done using 21-mm circular staplers. Distension with pressure up to 100 cm H2O was done on the anastomosed segment. Surface markers were tracked using a microscope and a CCD camera. Circumferential and longitudinal strains were computed. RESULTS: The staples restricted the deformation both in circumferential and longitudinal directions and induced a heterogeneous strain distribution. Circumferential strains were bigger between the staples (range 0.5 1) than inside the staples (range 0-0.3). The longitudinal strain ranged from 0 to slightly negative between the staples, indicating longitudinal compression. The negative strains turned into positive strains with increasing distance from the anastomosis. Further away from the anastomosis the longitudinal strain was in the range 0.3 to 0.5. CONCLUSION: The surface strain field was heterogeneously close to the stapled anastomosis. The longitudinal compression between staples in the longitudinal direction during inflation may have a beneficial effect preventing leakage, a phenomenon that needs further studies. The method may be useful in the design and validation of new staplers. PMID- 22075438 TI - STARR with PPH-01 and CCS30 contour Transtar for obstructed defecation syndrome. AB - INTRODUCTION: The stapled transanal rectal resection (STARR) procedure is safe and effective. OBJECTIVE OF THE STUDY: To compare STARR performed with PPH-01 (STARR) and CCS 30 (Transtar). MATERIALS AND METHODS: Sixty-four patients underwent STARR for obstructed defecation syndrome (32 STARR and 32 Transtar) and were observed from January 2007 to June 2009. Patients were studied by visit with questionnaires, colonoscopy or barium enema, defecography, and anorectal manometry. Postoperatively they were assessed through visit and questionnaires. RESULTS: All patients improved symptoms without statistical differences. The obstructed defecation syndrome score changed from 13 to 1.8 at 6 months and to 1 at 1 year in the STARR group (P < .05), and the score changed from 15 to 2 at 6 months and to 1 at 1 year in the Transtar group (P < .05). There were no intraoperative complications in the STARR group, but there were 2 dehiscences of suture in the Transtar group. There were no differences with regard to complications. CONCLUSION: Transtar is a more complex technique with more severe complications. A major resection is not always more effective. PMID- 22075439 TI - Risk factors and clinical presentation of cats with feline idiopathic cystitis. AB - Feline idiopathic cystitis (FIC) is the most common cause of feline lower urinary tract disease (FLUTD). This retrospective, case-controlled study evaluated possible risk factors associated with FIC and compared different clinical presentations in 64 cats with FIC. Several risk factors known to be involved in FLUTD were identified as playing a role in FIC. Of the stressful situations considered, most did not occur with increased frequency in cats with FIC compared to controls, except for a house move. The presence of pyuria, haematuria and an increased urine protein:creatinine ratio were significantly higher in obstructed males compared with non-obstructed males. An obstruction was significantly more likely in cats with struvite crystalluria compared with cats without struvite crystalluria. These findings suggest that urethral plugs might be an important cause or contributing factor of obstruction in FIC. Episodes of FIC seem to occur mainly in susceptible cats in combination with a deficient environment. PMID- 22075440 TI - Nuclear survivin expression is a positive prognostic factor in taxane-platinum treated ovarian cancer patients. AB - BACKGROUND: Survivin is an inhibitor of apoptosis and a regulator of mitotic progression. TP53 protein is a negative transcriptional regulator of survivin. The aim of our study was to evaluate the clinical significance of survivin expression in advanced stages ovarian cancer with respect to the TP53 status. METHODS: Survivin and TP53 expression was evaluated immunohistochemically in 435 archival samples of ovarian carcinomas (244 patients were treated with platinum/cyclophosphamide-PC/PAC; 191-with taxane-platinum (TP) agents). Univariate and multivariate statistical analyses were performed in patients groups divided according to the administered chemotherapeutic regimen, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively). RESULTS: Nuclear and cytoplasmic survivin expression was observed in 92% and 74% of the carcinomas, respectively. In patients treated with TP, high nuclear survivin expression decreased the risk of disease recurrence and death, and increased the probability of high platinum sensitivity (p < 0.01), but only in the TP53(+) group, and not in the TP53(-) group. CONCLUSIONS: It appears that TP53 status determines the clinical importance of nuclear survivin expression in taxane-platinum treated ovarian cancer patients. PMID- 22075441 TI - Visual inspection methods for cervical cancer prevention. AB - The need for simple, cost-effective screening approaches for cervical cancer prevention in low-resource countries has led to the evaluation of visual screening with 3-5% acetic acid. The low reproducibility and wide variation in accuracy reflect the subjective nature of the test. Pooled sensitivity, specificity, positive and negative predictive values were 80%, 92%, 10% and 99%, respectively, for detecting cervical intraepithelial neoplasia grade 2 or worse lesions. Realistic sensitivity of a quality- assured single visual inspection with acetic acid is around 50%. A single round of visual inspection with acetic acid screening has been associated with a 25-35% reduction in cervical cancer incidence and the frequency of cervical intraepithelial neoplasia grade 2 or worse lesions in randomised-controlled trials. Despite all its limitations, implementing visual inspection with acetic acid screening in low-resource countries may provide a pragmatic approach to building up human resources and infrastructure that may facilitate the highly anticipated low-cost, rapid human papilloma virus testing in the near future. PMID- 22075442 TI - UK guidance document: treatment of metastatic breast cancer. AB - Although there have been major improvements in the management of breast cancer, with a rapidly falling death rate despite an increasing incidence of the disease, metastatic breast cancer remains common and the cause of death in nearly 12 000 women annually in the UK. Numerous treatment options are available that either target the tumour or reduce the complications of the disease. Clinical decision making depends on knowledge of the extent and biology of the disease and available drug options, an understanding of the functional status, and also the wishes and expectations of the individual patient. In addition, the organisation of services and support of the patient are essential components of high-quality care. The National Institute for Health and Clinical Excellence (NICE) has produced guidelines for the treatment of advanced breast cancer, which in some areas have perhaps failed to appreciate the complexity of patient management. This guidance document aims to provide succinct practical advice on the treatment of metastatic breast cancer, highlight some limitations of the NICE guidelines, and provide suggestions for management where available data are limited. PMID- 22075443 TI - Treatment of glioblastoma multiforme - the Oxford Cancer Centre experience. PMID- 22075444 TI - Concurrent chemotherapy and intensity-modulated radiation therapy for anal carcinoma--clinical outcomes in a large National Cancer Institute-designated integrated cancer centre network. AB - AIMS: To report the clinical outcomes of patients with anal carcinoma treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy in a large integrated academic-community cancer centre network. MATERIALS AND METHODS: Seventy-eight patients were treated with IMRT for anal carcinoma at 13 community cancer centres. IMRT planning for all centres was carried out at one central location. Sixty-five patients (83%) were T1-T2, 64% were N0, 9% were M1; five patients were HIV positive. All but one patient received concurrent chemotherapy. The median dose to the pelvis including inguinal nodes was 45 Gy. The primary site and involved nodes were boosted to a median dose of 55.8 Gy. All acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: The median follow-up for the entire cohort was 16 months (range 0-72 months). Acute grade >=3 toxicity included 27.7% gastrointestinal and 29.0% dermatological. Acute grade 4 haematological toxicity occurred in 12.9% of patients. Sixty-four (88.9%) patients experienced a complete response. The 2 year colostomy-free survival, overall survival, freedom from local failure and freedom from distant failure rates were 81.2, 86.9, 83.6 and 81.8%, respectively. CONCLUSIONS: Early results seem to confirm that IMRT used concurrently with chemotherapy for treatment of anal carcinoma is effective and well tolerated. This complex treatment can be safely and effectively carried out in a large integrated healthcare network. PMID- 22075446 TI - The evolution of cefotaximase activity in the TEM beta-lactamase. AB - The development of a molecular-level understanding of drug resistance through beta-lactamase is critical not only in designing newer-generation antibacterial agents but also in providing insight into the evolutionary mechanisms of enzymes in general. In the present study, we have evaluated the effect of four drug resistance mutations (A42G, E104K, G238S, and M182T) on the cefotaximase activity of the TEM-1 beta-lactamase. Using computational methods, including docking and molecular mechanics calculations, we have been able to correctly identify the relative order of catalytic activities associated with these four single point mutants. Further analyses suggest that the changes in catalytic efficiency for mutant enzymes are correlated to structural changes within the binding site. Based on the energetic and structural analyses of the wild-type and mutant enzymes, structural rearrangement is suggested as a mechanism of evolution of drug resistance through TEM beta-lactamase. The present study not only provides molecular-level insight into the effect of four drug resistance mutations on the structure and function of the TEM beta-lactamase but also establishes a foundation for a future molecular-level analysis of complete evolutionary trajectory for this class of enzymes. PMID- 22075445 TI - Structural analyses of covalent enzyme-substrate analog complexes reveal strengths and limitations of de novo enzyme design. AB - We report the cocrystal structures of a computationally designed and experimentally optimized retro-aldol enzyme with covalently bound substrate analogs. The structure with a covalently bound mechanism-based inhibitor is similar to, but not identical with, the design model, with an RMSD of 1.4 A over active-site residues and equivalent substrate atoms. As in the design model, the binding pocket orients the substrate through hydrophobic interactions with the naphthyl moiety such that the oxygen atoms analogous to the carbinolamine and beta-hydroxyl oxygens are positioned near a network of bound waters. However, there are differences between the design model and the structure: the orientation of the naphthyl group and the conformation of the catalytic lysine are slightly different; the bound water network appears to be more extensive; and the bound substrate analog exhibits more conformational heterogeneity than typical native enzyme-inhibitor complexes. Alanine scanning of the active-site residues shows that both the catalytic lysine and the residues around the binding pocket for the substrate naphthyl group make critical contributions to catalysis. Mutating the set of water-coordinating residues also significantly reduces catalytic activity. The crystal structure of the enzyme with a smaller substrate analog that lacks naphthyl ring shows the catalytic lysine to be more flexible than in the naphthyl substrate complex; increased preorganization of the active site would likely improve catalysis. The covalently bound complex structures and mutagenesis data highlight the strengths and weaknesses of the de novo enzyme design strategy. PMID- 22075447 TI - Increasing compliance with protective eyewear to reduce ocular injuries in stone quarry workers in Tamil Nadu, India: a pragmatic, cluster randomised trial of a single education session versus an enhanced education package delivered over six months. AB - OBJECTIVE: To evaluate the efficacy of standard education versus enhanced education in increasing compliance with protective eyewear to prevent ocular injuries in stone-quarry workers. DESIGN: Pragmatic, allocation concealed, participant and outcome assessor blinded, cluster randomised trial. SETTING: Six stone-quarries around Vellore, Tamil Nadu, South India. PARTICIPANTS: 204 consenting adult stone quarry workers. INTERVENTIONS: Protective eyewear plus enhanced education (one education session, plus 11 sessions of group education, individual discussions, and educational plays over six months) versus protective eyewear plus standard education (one education session and 5 follow up visits). OUTCOMES: The primary outcomes were observer-rated compliance with protective eyewear and reduction in incidence of ocular injuries (slit-lamp examination by an observer blinded to allocation status) at three and six months. Analysis was by intention to treat. RESULTS: Quarries and participants were similar at enrolment. All quarries; 92/103 (90%) of workers in three quarries given enhanced intervention, and 91/101 workers (89%) in three quarries given standard education, completed six months follow up. Compared to standard education, enhanced education significantly increased compliance with protective eyewear by 16% (95% CI 3-28%) at three months (OR 2.1; 95% CI 1.2-3.8); and by 25% (95% CI 11-35%) at six months (OR 2.7; 95% CI 1.5-4.8). Protective eyewear and enhanced education reduced the incidence of eye injuries at three months by 16% (95% CI 7 24%); and standard education by 13% (95% CI 4-22%), compared to the three months before interventions. The cumulative reduction over baseline in eye injuries at the six months was greater with enhanced education (12% decrease; 95% CI 3-21%) than with standard education (7% decrease; 95% CI 17% decrease to 3% increase). However, this incidence did not differ significantly between intervention arms at three months (OR 0.7% 95% CI 0.3-2.1); and at six months (OR 0.8; 95% CI 0.4 1.5). CONCLUSION: Provision of appropriate protective eyewear reduces the incidence of eye injuries in stone-quarry workers. Periodic educational and motivational sessions with individuals and groups facilitates sustained use of protective eyewear. PMID- 22075448 TI - Combined posterior and medial plate fixation of complex proximal ulna fractures. PMID- 22075449 TI - Treatment of locally advanced pancreatic cancer: the role of radiation therapy. AB - Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy. PMID- 22075450 TI - Polymer drug-eluting stents: is the future biodegradable? PMID- 22075451 TI - Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. AB - BACKGROUND: The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. METHODS: We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS: 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18.7%) patients versus 192 (22.6%) patients (rate ratios [RR] 0.81, 95% CI 0.66-1.00, p for non-inferiority <0.0001, p for superiority=0.050). The RR of definite ST was 0.62 (0.35-1.08, p=0.09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0.20, 95% CI 0.06-0.67, p=0.004). Conversely, the RR of definite ST during the first year was 0.99 (0.51-1.95; p=0.98) and the test for interaction between RR of definite ST and time was positive (p(interaction)=0.017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0.86 (0.41-1.80) during the first year and 0.17 (0.04-0.78) during subsequent years (p(interaction)=0.049). INTERPRETATION: Biodegradable polymer BES are non inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. FUNDING: Biosensors Europe SA, Switzerland. PMID- 22075452 TI - Acute inhibition of the Na(+)/Ca(2+) exchanger reduces proarrhythmia in an experimental model of chronic heart failure. AB - BACKGROUND: Molecular remodeling in heart failure includes slowing of repolarization, leading to proarrhythmia. OBJECTIVE: To evaluate the effects of Na(+)/Ca(2+) exchanger (NCX) inhibition on repolarization as a novel antiarrhythmic concept in chronic heart failure (CHF). METHODS AND RESULTS: CHF was induced by rapid ventricular pacing in rabbits. Left ventricular function was assessed by echocardiography. Monophasic action potentials (MAPs) showed a prolongation of repolarization in CHF after atrioventricular block and stimulation at different cycle lengths. Sotalol (100 MUM, n = 13) or veratridine (0.5 MUM; n = 15) resulted in a further significant increase in the MAP duration. CHF was associated with an increased dispersion of repolarization, as compared with sotalol-treated (+22 +/- 7 ms; P < .05) and veratridine-treated (+20 +/- 6 ms; P < .05) sham hearts. In the presence of a low potassium concentration, sotalol and veratridine reproducibly induced early afterdepolarizations (EADs) and polymorphic ventricular tachyarrhythmias (VTs). SEA0400 (1 MUM), a pharmacological inhibitor of NCX, significantly shortened the MAP duration (P < .01) and reduced dispersion (P < .05). It suppressed EAD in 6 of 13 sotalol treated failing hearts and in 9 of 10 veratridine-treated failing hearts, leading to a reduction in VT (60% in sotalol-treated failing hearts and 83% in veratridine-treated failing hearts). Simulations using a mathematical model showed a reduction in the action potential duration and the number of EADs by the NCX block in all subgroups. CONCLUSIONS: In an experimental model of CHF, the acute inhibition of NCX (1) reduces the MAP duration, (2) decreases dispersion of repolarization, and (3) suppresses EAD and VT. Our observations indicate for the first time that pharmacological NCX inhibition increases repolarization reserve and protects against VTs in heart failure. PMID- 22075453 TI - Transcriptional profiling of human skin fibroblast cell line Hs27 induced by herbal formula Astragali Radix and Rehmanniae Radix. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The herbs Astragali Radix (AR) and Rehmanniae Radix (RR) have long been used in traditional Chinese Medicine and serve as the principal herbs in treating diabetic foot ulcer. AIM OF THE STUDY: Chinese herbal formulus comprising Astragali Radix (AR) and Rehmanniae Radix (RR) have been shown to improve the healing of diabetic foot ulcer through enhancing the viability of primary fibroblasts in diabetic patients suffering insulin resistance. Our previous study demonstrated that the herbal formula NF3 comprising of AR and RR in the ratio of 2:1 was effective in promoting wound healing in diabetic rats, and in vitro data indicated that the wound healing effects of NF3 might be due to the regulation and coordination of inflammation, angiogenesis and tissue regeneration. However, the underlying molecular mechanism has not been well investigated. In this study, we investigated the cellular and molecular effects of the herbal formula NF3 on human skin fibroblast cells. MATERIALS AND METHODS: Human skin fibroblast cells Hs27 were treated with NF3 ranging from 0 to 8 mg/ml for 24h, and the cells without NF3 treatment were used as control. Cell proliferation assay and cell cycle analysis were performed. Transcriptional profiles of Hs27 cells upon NF3 treatment were acquired by using a human cDNA microarray containing 10,000 genes, and the signaling pathways differentially regulated by NF3 were identified and analyzed. RESULTS: NF3 promoted Hs27 cell proliferation and cell cycle progression. Microarray analysis revealed that 116 genes were differentially expressed upon NF3 treatment. Functional analysis of the genes indicated that NF3 mainly activated Wnt and angiogenesis related pathways, which are directly related to cell proliferation, angiogenesis, extracellular matrix (ECM) formation and inflammation during the process of wound healing. CONCLUSION: This study provides insight into the molecular mechanism of how the herbal formula Astragali Radix and Rehmanniae Radix may serve as potential therapeutics for wound healing. PMID- 22075454 TI - Catechol alkenyls from Semecarpus anacardium: acetylcholinesterase inhibition and binding mode predictions. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Semecarpus anacardium L. f. (Anacardiaceae) are used in Ayurvedic medicine and also in Iranian Traditional Medicine for various indications, among those for retarding and treatment of dementia. AIM OF THE STUDY: The severity of Alzheimer's disease obviously correlates with a cholinergic deficit. In a screening for acetylcholinesterase (AChE) inhibitory activity, an extract from the fruit resin of Semecarpus anacardium was among the most active ones. Thus, the aim of this study was to isolate the active compounds and to investigate them in detail. Their binding mode to the active site of AChE was investigated by in silico docking experiments. MATERIALS AND METHODS: From a dichloromethane extract in an activity guided fractionation the active compounds were isolated under use of different chromatographic techniques. Their structures were unambiguously identified by one and two-dimensional (1)H and (13)C NMR spectroscopy and mass spectrometry and their cholinesterase inhibitory activities were determined by a microplate assay. In order to compare the 3D active sites of AChE from Torpedo californica (TcAChE) and from Electrophorus electricus (EeAChE), three files from the Protein Data Bank (PDB) were used and for docking experiments, GOLD 3.1 software was employed. The concentrations of active compounds in the extract and the fruits were determined by HPLC analysis. RESULTS: The active compounds were determined as 1',2'-dihydroxy-3'-pentadec-8-enylbenzene (A) and 1',2'-dihydroxy-3'-pentadeca 8,11-dienylbenzene (B). Their IC(50) values in an in vitro assay on AChE inhibition were determined as 12 and 34 MUg/mL, respectively, while they were not active in the inhibition of butyrylcholinesterase (BChE). In silico docking experiments showed a similar bioactivity for compounds A and B. The concentration of compounds A and B in the fruits was 1.85% and 1.88%, respectively. CONCLUSION: In the search for the active principle of the fruit resin of Semecarpus anacardium, compounds A and B were identified as two selective inhibitors for AChE versus BChE. PMID- 22075455 TI - In vitro antimicrobial synergism within plant extract combinations from three South African medicinal bulbs. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tulbaghia violacea, Hypoxis hemerocallidea and Merwilla plumbea are used in South African traditional medicine for the treatment of some infectious diseases and other ailments. AIM OF THE STUDY: The study aimed at investigating the antimicrobial efficacies of independent and various within plant extract combinations of three medicinal bulbs to understand the possible pharmacological interactions. MATERIALS AND METHODS: Bulb and leaf extracts of the three medicinal plants, independently and in combinations, were comparatively assessed for antimicrobial activity against two Gram-positive and two Gram negative bacteria and Candida albicans using the microdilution method. The fractional inhibitory concentration indices (FIC) for two extract combinations were determined. RESULTS: At least one extract combination in each plant sample demonstrated good antimicrobial activity against all the test organisms. The efficacies of the various extract combinations in each plant sample varied, with the strongest synergistic effect exhibited by the proportional extract yield combination of PE and DCM extracts in Merwilla plumbea bulb sample against Staphylococcus aureus (FIC index of 0.1). Most extract combinations demonstrated either a synergistic, additive or indifferent interaction effect against the test bacteria with only a few exhibiting antagonistic effects. CONCLUSION: The observed antimicrobial efficacy and synergistic interactions indicate the beneficial aspects of combination chemotherapy of medicinal plant extracts in the treatment of infectious diseases. PMID- 22075456 TI - Diuretic, anti-inflammatory, and analgesic activities of the ethanol extract from Cynoglossum lanceolatum. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Cynoglossum lanceolatum Forsk. (Boraginaceae) has been used in folk medicine in china to treat acute nephritis, periodontitis, acute submandibular lymphadenitis, snake bite, etc. However, there have been no scientific reports in the modern literature on the diuretic, anti-inflammatory and analgesic effects of this plant. The objective of this study is to evaluate the above activities of the Cynoglossum lanceolatum extract (CLE) in animals. MATERIALS AND METHODS: The diuretic effect of CLE was assessed in rats and rabbits. The anti-inflammatory activity was evaluated using fresh egg white induced paw edema in rats, carrageenan-elicited paw edema in adrenalectomized rats, and dimethylbenzene-induced inflammation in mice. The analgesic action was estimated in mice using the acetic acid-induced writhing test and the hot-plate test. In addition, the acute oral toxicity of CLE was studied in mice. RESULTS: CLE strikingly and dose-dependently increased urine output of rats and rabbits, suppressed fresh egg white-induced paw edema in rats and carrageenan-elicited paw edema in adrenalectomized rats, reduced dimethylbenzene-induced ear edema in mice, inhibited the writhing response in mice, but did not increased reaction time of mice in the hot-plate test. No death of mice was observed when orally administered CLE up to 12g/kg. CONCLUSIONS: These findings propose that CLE has evident diuretic, anti-inflammatory, and non-central analgesic activities. Furthermore the anti-inflammatory action does not rely on endogenetic glucocorticoids regulated by hypothalamo-pituitary-adrenal axis. On the other hand, CLE also shows a favorable safety. PMID- 22075457 TI - Potency testing of veterinary vaccines: the way from in vivo to in vitro. AB - Current quality control of inactivated animal vaccines still focuses on the potency of final products in a batch-wise manner. Animal welfare concerns as well as scientific considerations have led to the '3Rs-concept' that comprises the refinement of animal procedures, the reduction of animal numbers, and the replacement of animal models. Although the 3Rs-concept has been widely accepted as a fundamental principle, the number of approved alternatives for in vivo tests is still limited. To promote further progress, the international scientific workshop 'Potency Testing of Veterinary Vaccines: The Way from in vivo to in vitro' was held at the Paul-Ehrlich-Institut in Langen, Germany, on 01-03 December 2010. More than 130 participants from industry, academia and regulatory authorities discussed the current state of the 3Rs-concept, examples of its successful implementation as well as still existing hurdles. Special emphasis was laid on the 'consistency approach' that aims to ensure relevant quality attributes of vaccine batches by in vitro analyses during production rather than by in vivo potency tests on the final product. This report provides an overview of the insights gained, including the recommendations produced at the end of the workshop. PMID- 22075458 TI - [Obesity and homeostatic inflammation]. PMID- 22075459 TI - [Role of chronic inflammation in the pathogenesis of atherosclerosis]. PMID- 22075460 TI - [Role of 12/15 lipoxygenase-induced inflammation in heart failure]. PMID- 22075461 TI - [Atrial fibrillation and inflammation]. PMID- 22075462 TI - [Mechanosensing of blood flow in vascular endothelial cells]. PMID- 22075463 TI - [Clinical development of new drugs and pharmacology]. PMID- 22075464 TI - [Good clinical practice (GCP) in clinical trials]. PMID- 22075465 TI - [Anti-tumor mechanism and clinical efficacy of Eribulin (Halaven(r)), a new microtubulin inhibitor approved for treatment of metastatic breast cancer]. PMID- 22075466 TI - Application of classic utilities to published pediatric cost-utility studies. AB - OBJECTIVE: Economic analyses, such as cost-utility analyses (CUAs), are dependent on the quality of the data used. Our objective was to test how health utility values (measurements of patient preference) assessed by recommended methods (classic utilities) would impact the conclusions in published pediatric CUAs. METHODS: Classic utilities for pediatric health states were obtained by recommended utility assessment methods, time trade-off, and standard gamble in 4016 parent interviews. To test the impact of these utilities on published studies, we obtained a sample of published pediatric CUAs by searching Medline, EMBASE, EconLit, Health Technology Assessment Database, Cochrane Database on Systematic Reviews, Database of Abstracts of Reviews of Effects, and the Cost Effective Analysis (CEA) Registry at Tufts Medical Center, using search terms for cost-utility analysis. Articles were included when results were presented as cost per quality adjusted life-years (QALYs), the interventions were for children <18 years of age and included at least one of the following health states: attention deficit hyperactivity disorder, asthma, gastroenteritis, hearing loss, mental retardation, otitis media, seizure disorder, or vision loss. Studies that did not include these or equivalent health states were excluded. For each CUA, we determined utilities (values for patient preference), the utility assessment method used, and presence of one-way sensitivity analyses (SAs) on utilities. When one-way SAs were conducted, we determined if using our classic utilities would change the result of the CUA. When an SA was not presented, we determined if using our classic utilities would tend to support or not support the published conclusions. RESULTS: We evaluated 39 articles. Eighteen articles presented results of one-way SAs on utilities. Seven articles presented SAs over a range that included our classic utilities. In 4 of the 7, using classic utilities would change the conclusion of the study. For the 32 articles where no one-way SA were presented (n = 21), or where the classic utilities fell outside the range tested (n =11), a change to classic utility would tend against the study conclusion in 12 articles (31%). CONCLUSIONS: More than a third of published CUA studies could change if pediatric utilities obtained by recommended, classic methods were used. One-way SAs on utilities are often not presented, making comparison between studies challenging. PMID- 22075467 TI - Well-child care practice redesign for low-income children: the perspectives of health plans, medical groups, and state agencies. AB - OBJECTIVE: The aim of this study was to examine the views of key stakeholders in health care payer organizations on the use of practice redesign strategies to improve the delivery of well-child care (WCC) to low-income children aged 0 to 3 years. METHODS: We conducted semistructured interviews with 18 key stakeholders (eg, chief medical officers, medical directors) in 11 California health plans and 2 medical group organizations serving low-income children, as well as the 2 state agencies that administer the 2 largest low-income insurance programs for California children. Discussions were recorded, transcribed, and analyzed using the constant comparative method of qualitative analysis. RESULTS: Participants reported that nonphysicians were underutilized as WCC providers, and group visits and Internet services were likely a more effective way to provide anticipatory guidance and behavioral/developmental services. Participants described barriers to redesign, including the start-up costs required to implement redesign as well as a lack of financial incentives to support innovation in WCC delivery. Participants suggested solutions to these barriers, including using pay-for performance programs to reward practices that expanded WCC services, and providing practices with start-up grants to implement pilot redesign projects that would eventually become self-sustaining. State-level barriers included poor Medicaid reimbursement rates and disincentives to innovation created by current Healthcare Effectiveness Data and Information Set measures. CONCLUSIONS: All stakeholders will ultimately be needed to support WCC redesign; however, California payers may need to provide logistic, design, and financial support to practices, whereas state agencies may need to reshape the incentives to reward innovation around child preventive health and developmental services. PMID- 22075468 TI - 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. PMID- 22075469 TI - 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. PMID- 22075470 TI - Acute macrophysiological effects of pericardiectomy: chronic effects of pericardiectomy/pericardiotomy uninvestigated - is pericardiectomy benign? PMID- 22075471 TI - Expression of NADPH oxidase by trophoblast cells: potential implications for the postimplanting mouse embryo. AB - Cytochemical localization of hydrogen peroxide-generating sites suggests NADPH (nicotinamide adenine dinucleotide 3-phosphate [reduced form]) oxidase expression at the maternal-fetal interface. To explore this possibility, we have characterized the expression and activity of the NADPH oxidase complex in trophoblast cells during the postimplantation period. Implantation sites and ectoplacental cones (EPCs) from 7.5-gestational day embryos from CD1 mice were used as a source for expression analyses of NADPH oxidase catalytic and regulatory subunits. EPCs grown in primary culture were used to investigate the production of superoxide anion through dihydroxyethidium oxidation in confocal microscopy and immunohistochemical assays. NADPH subunits Cybb (gp91phox), Cyba (p22phox), Ncf4 (p40phox), Ncf1 (p47phox), Ncf2 (p67phox), and Rac1 were expressed by trophoblast cells. The fundamental subunits of membrane CYBB and cytosolic NCF2 were markedly upregulated after phorbol-12-myristate-13-acetate (PMA) treatment, as detected by quantitative real-time PCR, Western blotting, and immunohistochemistry. Fluorescence microscopy imaging showed colocalization of cytosolic and plasma membrane NADPH oxidase subunits mainly after PMA treatment, suggesting assembly of the complex after enzyme activation. Cultured EPCs produced superoxide in a NADPH-dependent manner, associating the NADPH oxidase mediated superoxide production with postimplantation trophoblast physiology. NADPH-oxidase cDNA subunit sequencing showed a high degree of homology between the trophoblast and neutrophil isoforms of the oxidase, emphasizing a putative role for reactive oxygen species production in phagocytic activity and innate immune responses. PMID- 22075472 TI - Hemodynamic, vascular, and reproductive impact of FMS-like tyrosine kinase 1 (FLT1) blockade on the uteroplacental circulation during normal mouse pregnancy. AB - To investigate the role of FMS-like tyrosine kinase 1 (FLT1, also known as VEGFR1) signaling during pregnancy, mice were injected with anti-FLT1 neutralizing antibody (Ab) beginning on Gestational Day 8 or 12 and every other day thereafter until Day 18; vehicle-only injected mice served as controls. Uterine artery blood flow was measured with ultrasound on Days 13 and 18, and morphometric measurements of the uterine arcade were carried out on Day 19 to provide a measure of gestational vascular remodeling; reproductive performance was evaluated by determining litter size, resorption rates, and pup and placental weights. Ab injections beginning on Day 8 or Day 12 resulted in significant reductions of uterine artery peak systolic and diastolic flows at Days 13 and 18. In addition, normal reproductive function was compromised, as evidenced by a significant reduction in average number of viable pups along with enhanced resorption rates. Reproductive performance was also significantly compromised in this group, although less severely. There was no evidence of a reduction in main uterine artery diameters, though arterial distensibility was reduced, and the diameter of the main uterine vein was significantly smaller in the Ab-injected mice. Significant reductions in main uterine artery and segmental artery length were also noted. Placental and pup weights were similar in all the groups. FLT1 inhibition during murine pregnancy impaired blood flow to the fetal-placental unit, compromised several indices of vascular remodeling, reduced fecundity, and increased fetal reabsorptions. The effects of FLT1 inhibition are most pronounced when targeted during early pregnancy. PMID- 22075473 TI - Loss of calcium in human spermatozoa via EPPIN, the semenogelin receptor. AB - The development of a new male contraceptive requires a transition from animal model to human and an understanding of the mechanisms involved in the target's inhibition of human spermatozoan fertility. We now report that semenogelin (SEMG1) and anti-EPPIN antibodies to a defined target site of 21 amino acids on the C terminal of EPPIN cause the loss of intracellular calcium, as measured by Fluo-4. The loss of intracellular calcium explains our previous observations of an initial loss of progressive motility and eventually the complete loss of motility when spermatozoa are treated with SEMG1 or anti-EPPIN antibodies. Thimerosal can rescue the effects of SEMG1 on motility, implying that internal stores of calcium are not depleted. Additionally, SEMG1 treatment of spermatozoa decreases the intracellular pH, and motility can be rescued by ammonium chloride. The results of this study demonstrate that EPPIN controls sperm motility in the ejaculate by binding SEMG1, resulting in the loss of calcium, most likely through a disturbance of internal pH and an inhibition of uptake mechanisms. However, the exact steps through which the EPPIN-SEMG1 complex exerts its effect on internal calcium levels are unknown. Anti-EPPIN antibodies can substitute for SEMG1, and, therefore, small-molecular weight compounds that mimic anti-EPPIN binding should be able to substitute for SEMG1, providing the basis for a nonantibody, nonhormonal male contraceptive. PMID- 22075474 TI - Differential gene expression profile in bovine blastocysts resulting from hyperglycemia exposure during early cleavage stages. AB - To understand the compromised survival of embryos derived from assisted reproductive techniques, transcriptome survey of early embryonic development has shown the impact of in vitro culture environment on gene expression in bovine or other living species. However, how the differentially expressed genes translate into developmentally compromised embryos is unresolved. We therefore aimed to characterize transcriptomic markers expressed by bovine blastocysts cultured in conditions that are known to impair embryo development. As increasing glucose concentrations has been shown to be stressful for early cleavage stages of mammalian embryos and to decrease subsequent blastocyst survival, in vitro matured/fertilized bovine zygotes were cultured in control (0.2 mM) or high glucose (5 mM) conditions until the 8- to 16-cell stage, and then transferred to control media until they reached the blastocyst stage. The concentration of 5 mM glucose was chosen as a stress treatment because there was a significant effect on blastocyst rate without the treatment's being lethal as with 10 mM. Microarray analysis revealed gene expression differences unrelated to embryo sex or hatching. Overrepresented processes among differentially expressed genes in treated blastocysts were extracellular matrix signalling, calcium signaling, and energy metabolism. On a pathophysiological level, higher glucose treatment impacts pathways associated with diabetes and tumorigenesis through genes controlling the Warburg effect, i.e., emphasis on use of anaerobic glycolysis rather than oxidative phosphorylation. These results allowed us to conclude that disruption of in vitro preattachment development is concomitant with gene expression modifications involved in metabolic control. PMID- 22075475 TI - Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype. AB - Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties of mesenchymal stem cells (MSCs), has been characterized. The endometrial MSC (eMSC) is likely the precursor of the endometrial stromal fibroblast. The goal of this study was to determine the transcriptome and signaling pathways in the eMSC to understand its functional phenotype. Endometrial stromal cells from oocyte donors (n = 20) and patients undergoing benign gynecologic surgery (n = 7) were fluorescence-activated cell sorted into MCAM (CD146)(+)/PDGFRB(+) (eMSC), MCAM (CD146)(-)/PDGFRB(+) (fibroblast), and MCAM (CD146)(+)/PDGFRB(-) (endothelial) populations. The eMSC population contained clonogenic cells with a mesenchymal phenotype differentiating into adipocytes when cultured in adipogenic medium. Gene expression profiling using Affymetrix Human Gene 1.0 ST arrays revealed 762 and 1518 significantly differentially expressed genes in eMSCs vs. stromal fibroblasts and eMSCs vs. endothelial cells, respectively. By principal component and hierarchical clustering analyses, eMSCs clustered with fibroblasts and distinctly from endothelial cells. Endometrial MSCs expressed pericyte markers and were localized by immunofluorescence to the perivascular space of endometrial small vessels. Endometrial MSCs also expressed genes involved in angiogenesis/vasculogenesis, steroid hormone/hypoxia responses, inflammation, immunomodulation, cell communication, and proteolysis/inhibition, and exhibited increased Notch, TGFB, IGF, Hedgehog, and G-protein-coupled receptor signaling pathways, characteristic of adult tissue MSC self-renewal and multipotency. Overall, the data support the eMSC as a clonogenic, multipotent pericyte that displays pathways of self-renewal and lineage specification, the potential to respond to conditions during endometrial desquamation and regeneration, and a genetic program predictive of its differentiated lineage, the stromal fibroblast. PMID- 22075476 TI - Metastasis-associated protein 3 (MTA3) regulates G2/M progression in proliferating mouse granulosa cells. AB - Metastasis-associated protein 3 (MTA3) is a constituent of the Mi-2/nucleosome remodeling and deacetylase (NuRD) protein complex that regulates gene expression by altering chromatin structure and can facilitate cohesin loading onto DNA. The biological function of MTA3 within the NuRD complex is unknown. Herein, we show that MTA3 was expressed highly in granulosa cell nuclei of all ovarian follicle stages and at lower levels in corpora lutea. We tested the hypothesis that MTA3 NuRD complex function is required for granulosa cell proliferation. In the ovary, MTA3 interacted with NuRD proteins CHD4 and HDAC1 and the core cohesin complex protein RAD21. In cultured mouse primary granulosa cells, depletion of endogenous MTA3 using RNA interference slowed cell proliferation; this effect was rescued by coexpression of exogenous MTA3. Slowing of cell proliferation correlated with a significant decrease in cyclin B1 and cyclin B2 expression. Granulosa cell populations lacking MTA3 contained a significantly higher percentage of cells in G2/M phase and a lower percentage in S phase compared with control cells. Furthermore, MTA3 depletion slowed entry into M phase as indicated by reduced phosphorylation of histone H3 at serine 10. These findings provide the first evidence to date that MTA3 interacts with NuRD and cohesin complex proteins in the ovary in vivo and regulates G2/M progression in proliferating granulosa cells. PMID- 22075477 TI - Initiating meiosis: the case for retinoic acid. AB - The requirement for vitamin A in reproduction and development was first determined from studies of nutritional deficiencies. Subsequent research has shown that embryonic development and both male and female reproduction are modulated by retinoic acid (RA), the active form of vitamin A. Because RA is active in multiple developmental systems, its synthesis, transport, and degradation are tightly regulated in different tissues. A growing body of evidence implicates RA as a requirement for the initiation of meiosis in both male and female mammals, resulting in a mechanistic model involving the interplay of RA, RA synthesis enzymes, RA receptors, and degradative cytochrome P450 enzymes in this system. Recently, that model has been challenged, prompting a review of the established paradigm. While it remains possible that additional molecules may be involved in regulating entry into meiosis, the weight of evidence supporting a key role for RA is incontrovertible. PMID- 22075478 TI - Residual sleep-disordered breathing during autotitrating continuous positive airway pressure therapy. AB - Obstructive sleep apnoea (OSA) is often treated with autotitrating continuous positive airway pressure (autoCPAP) devices. Clinical and bench tests of these devices have suggested performance limitations. These studies do not indicate whether this is a failure to detect or a failure to respond to airway obstruction. In this randomised, crossover trial, 34 patients with moderate-to severe OSA underwent polysomnography on two laboratory visits. The autoCPAP device was randomly set to a fixed subtherapeutic pressure (detection assessment) or autotitrating mode (response assessment). Airflow was measured both from the autoCPAP (autoCPAP flow) and directly from the nasal mask, and recorded on polysomnography. Apnoea/hypopnoea indices (AHIs) measured at the two sites and from the autoCPAP download report were compared. Regarding detection, the AHI measured from the nasal mask showed good agreement with the autoCPAP flow AHI, but agreement was lower with the autoCPAP report AHI. In autotitrating mode, there was significant misclassification of those with and without OSA (AHI >= 10 events . h(-1)) on the autoCPAP report. Regarding response, residual OSA (AHI >= 10 events . h(-1)) was still evident in 24% of patients during autotitration. In some patients, autoCPAP fails to detect and/or respond to sleep apnoea. Clinicians should consider limitations of each device and use caution when using autoCPAP report statistics to verify effective treatment. PMID- 22075479 TI - Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting? AB - Information regarding the utility of adjunct diagnostic tests in combination with Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is limited. We hypothesised adjunct tests could enhance accuracy and/or reduce the cost of tuberculosis (TB) diagnosis prior to MTB/RIF testing, and rule-in or rule-out TB in MTB/RIF negative individuals. We assessed the accuracy and/or laboratory-associated cost of diagnosis of smear microscopy, chest radiography (CXR) and interferon-gamma release assays (IGRAs; T-SPOT-TB (Oxford Immunotec, Oxford, UK) and QuantiFERON TB Gold In-Tube (Cellestis, Chadstone, Australia)) combined with MTB/RIF for TB in 480 patients in South Africa. When conducted prior to MTB/RIF: 1) smear microscopy followed by MTB/RIF (if smear negative) had the lowest cost of diagnosis of any strategy investigated; 2) a combination of smear microscopy, CXR (if smear negative) and MTB/RIF (if imaging compatible with active TB) did not further reduce the cost per TB case diagnosed; and 3) a normal CXR ruled out TB in 18% of patients (57 out of 324; negative predictive value (NPV) 100%). When downstream adjunct tests were applied to MTB/RIF-negative individuals, radiology ruled out TB in 24% (56 out of 234; NPV 100%), smear microscopy ruled in TB in 21% (seven out of 24) of culture-positive individuals and IGRAs were not useful in either context. In resource-poor settings, smear microscopy combined with MTB/RIF had the highest accuracy and lowest cost of diagnosis compared to either technique alone. In MTB/RIF-negative individuals, CXR has poor rule-in value but can reliably rule out TB in approximately one in four cases. These data inform upon the programmatic utility of MTB/RIF in high-burden settings. PMID- 22075480 TI - Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma. AB - Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM using case-control data in male subjects. Cases were selected from a French case-control study conducted in 1987 1993 and the French National Mesothelioma Surveillance Program in 1998-2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job-exposure matrix. The dose response relationships were estimated using restricted cubic spline functions in logistic regression models. A total of 2,466 ever-asbestos-exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 yrs and continued to increase until 30 yrs after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased. These results, based on a large population-based case-control study, underline the need to take into account the temporal pattern of exposure on risk assessment. PMID- 22075481 TI - Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema. AB - The need for a less invasive procedure than surgical lung volume reduction that can produce consistent improvements with reduced morbidity remains a medical goal in patients with emphysema. We sought to determine the effect of bronchoscopic thermal vapour ablation (BTVA) on lung volumes and outcomes in patients with emphysema. 44 patients with upper lobe-predominant emphysema were treated unilaterally with BTVA. Entry criteria included: age 40-75 yrs, forced expiratory volume in 1 s (FEV(1)) 15-45% predicted, previous pulmonary rehabilitation and a heterogeneity index (tissue/air ratio of lower lobe/upper lobe) from high resolution computed tomography (HRCT) >= 1.2. Changes in FEV(1), St George's Respiratory Questionnaire (SGRQ), 6-min walk distance (6 MWD), modified Medical Research Council (mMRC) dyspnoea score, and hyperinflation were measured at baseline, and 3 and 6 months post-BTVA. At 6 months, mean +/- SE FEV(1) improved by 141 +/- 26 mL (p<0.001) and residual volume was reduced by 406 +/- 113 mL (p<0.0001). SGRQ total score improved by 14.0 +/- 2.4 points (p<0.001), with 73% improving by >= 4 points. Improvements were observed in 6 MWD (46.5 +/- 10.6 m) and mMRC dyspnoea score (0.9 +/- 0.2) (p<0.001 for both). Lower respiratory events (n=11) were the most common adverse event and occurred most often during the initial 30 days. BTVA therapy results in clinically relevant improvements in lung function, quality of life and exercise tolerance in upper lobe predominant emphysema. PMID- 22075482 TI - Metabolic syndrome, insulin resistance and sleepiness in real-life obstructive sleep apnoea. AB - The metabolic syndrome shows a variable prevalence in obstructive sleep apnoea (OSA), and its association with insulin resistance or excessive daytime sleepiness in OSA is unclear. This study assessed the following in consecutive patients with newly diagnosed OSA: 1) the prevalence of metabolic syndrome; and 2) its association with insulin resistance and daytime sleepiness. Metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III criteria), insulin resistance (Homeostatic Model Assessment (HOMA) index, n = 288) and daytime sleepiness (Epworth Sleepiness Scale) were assessed in 529 OSA patients. The prevalence of metabolic syndrome was 51.2%, which increased with OSA severity. Each metabolic syndrome component correlated with apnoea/hypopnoea index, but only blood pressure retained significance after correction for confounders. Both obesity and OSA contributed to metabolic abnormalities, with different sex-related patterns, since diagnosis of metabolic syndrome was significantly associated with neck circumference, age, body mass index and lowest arterial oxygen saturation in males, and with age and arousal index in females. The number of metabolic syndrome components increased with HOMA index (p<0.001). Prevalence of sleepiness was the same in patients with and without metabolic syndrome. The metabolic syndrome occurs in about half of "real-life" OSA patients, irrespective of daytime sleepiness, and is a reliable marker of insulin resistance. PMID- 22075483 TI - Clonality of multifocal nonsmall cell lung cancer: implications for staging and therapy. AB - Nonsmall cell lung cancers (NSCLCs) display a variety of morphological and molecular features. Accurate subtyping of NSCLC has been shown to predict patient survival as well as response rates and toxicities of specific drugs. Assessment of multifocal lung tumours and the distinction of synchronous primary tumours from intrapulmonary metastases represent an important problem as this decision significantly influences tumour staging and subsequent treatment strategies. In order to provide a basis for evidence-based treatment decisions in these patients, we analysed the clonal relationship of multifocal NSCLC with indistinguishable histomorphology in a series of 78 patients by allelotyping (using polymorphic short tandem repeat markers) as well as KRAS and epidermal growth factor receptor (EGFR) mutation testing. Our data demonstrate a common clonal origin indicative of intrapulmonary metastases in almost two-thirds (~62%) of the cases, while ~36% of multifocal NSCLC displayed unique molecular profiles suggesting separate primary tumours. Divergent KRAS and/or EGFR mutations were observed in ~8% of all cases. With the increased availability of EGFR-targeted therapy options, nonresectable, multifocal NSCLC with diverging KRAS and/or EGFR mutations are likely to show different treatment responses, underlining the need to separately analyse multifocal tumours. Obviously, this also holds true for further, novel molecular predictors of targeted therapies. PMID- 22075484 TI - beta2-adrenergic receptor polymorphisms, asthma and COPD: two large population based studies. AB - The beta(2)-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone. We tested the hypothesis that three functional polymorphisms in the ADRB2 gene (Thr164Ile, Gly16Arg and Gln27Glu) are associated with reduced lung function, asthma or chronic obstructive pulmonary disease (COPD). We first genotyped 8,971 individuals from the Copenhagen City Heart Study for all three polymorphisms. To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism. We identified 60,910 Thr164Ile noncarriers, 1,822 heterozygotes and 16 homozygotes. In the Copenhagen City Heart Study, the Thr164Ile genotype was associated with reduced forced expiratory volume in 1 s (FEV(1)) % predicted (trend p = 0.01) and FEV(1)/forced vital capacity (FVC) (p = 0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV(1) % pred and FEV(1)/FVC, respectively, compared with noncarriers. The odds ratio for COPD in Thr164Ile heterozygotes was 1.46 (95% CI 1.05-2.02). In the Copenhagen General Population Study, the Thr164 genotype associated with reduced FEV(1) % pred (p = 0.04) and FEV(1)/FVC (p < 0.001): Thr164Ile homozygotes and heterozygotes had 7% and 1% reduced FEV(1) % pred and 6% and 1% reduced FEV(1)/FVC, respectively, compared with noncarriers. The odds ratios for COPD in Thr164Ile homozygotes and heterozygotes were 4.53 (95% CI 1.54-13.3) and 1.07 (95% CI 0.92-1.25), respectively. Our results suggest that ADRB2 Thr164Ile is associated with reduced lung function and increased risk of COPD in the general population. PMID- 22075485 TI - Pre-natal exposure to dichlorodiphenyldichloroethylene and infant lower respiratory tract infections and wheeze. AB - The aim of our study was to examine whether pre-natal exposure to dichlorodiphenyldichloroethylene (DDE) increases the risk of lower respiratory tract infections (LRTIs) and wheeze in infants. The study is based on a birth cohort of 1,455 mother-child pairs. Maternal serum concentrations of DDE, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) were measured during pregnancy. Parental reports on LRTI and wheeze were obtained when children were 12-14 months old. 35.4% of children developed at least one LRTI episode and 33.6% at least one wheezing episode during their first 12-14 months of life. Median DDE, PCBs and HCB concentrations were 116.3, 113.7 and 46.4 ng . g(-1) lipid, respectively. DDE concentrations were associated with LRTI risk (relative risk (RR) per 10% increase 1.11, 95% CI 1.00-1.22), also after adjustment for PCBs and HCB. In all quartiles of DDE exposure, the risk of LRTI was increased compared with the lowest quartile, but the increase was statistically significant only in the third quartile (RR 1.33, 95% CI 1.08-1.62). No association was observed for PCBs and HCB. Results were similar for wheeze. This study suggests that pre-natal DDE exposure is associated with a higher risk of LRTI and wheeze in infants independently of exposure to other organochlorine compounds. PMID- 22075486 TI - Stage IV sarcoidosis: comparison of survival with the general population and causes of death. AB - The objectives of this study were to compare the survival of sarcoid patients with pulmonary fibrosis with that of the general population and to determine the causes of death and the incidence of evolutive complications. This retrospective cohort included 142 sarcoid patients in radiographic stage IV (74 males; mean +/- SD age 48.1 +/- 12 yrs). Their survival was compared with that of the general French population, matched for the year and age at diagnosis of stage IV disease, sex and length of follow-up. Expected survival probabilities were calculated year by-year on the basis of probabilities provided by official demographic data for France. Survival curves were based on the Kaplan-Meier method and compared using the log-rank test. During the follow-up period (7.1 +/- 4.8 yrs), pulmonary hypertension (PH) was observed in 29.7% of cases and aspergilloma in 11.3%. Long term oxygen therapy was required in 12%. Survival was 84.1% at 10 yrs, which was worse than for the general population (p = 0.013). 16 (11.3%) patients died from the following causes: refractory PH (n = 5), chronic respiratory insufficiency (n = 4), acute respiratory insufficiency (n = 2), haemoptysis due to aspergilloma (n = 1), heart sarcoidosis (n = 1), nocardiosis (n = 1) and unknown causes (n = 2). Survival is significantly decreased in stage IV patients. 75% of fatalities are directly attributable to respiratory causes. PMID- 22075487 TI - Non-CPAP therapies in obstructive sleep apnoea: mandibular advancement device therapy. AB - Mandibular advancement devices (MADs) represent the main non-continuous positive airway pressure (non-CPAP) therapy for patients with obstructive sleep apnoea (OSA). The aim of the European Respiratory Society Task Force was to review the evidence in favour of MAD therapy. Effects of tongue-retaining devices are not included in this report. Custom-made MADs reduce apnoea/hypopnoea index (AHI) and daytime sleepiness compared with placebo devices. CPAP more effectively diminishes AHI, while increasing data suggest fairly similar outcomes in relation to symptoms and cardiovascular health from these treatments. Patients often prefer MADs to CPAP. Milder cases and patients with a proven increase in upper airway size as a result of mandibular advancement are most likely to experience treatment success with MADs. A custom-made device titrated from an initial 50% of maximum mandibular advancement has been recommended. More research is needed to define the patients who will benefit from MAD treatment compared with CPAP, in terms of the effects on sleep-disordered breathing and on other diseases related to OSA. In conclusion, MADs are recommended for patients with mild to moderate OSA (Recommendation Level A) and for those who do not tolerate CPAP. The treatment must be followed up and the device adjusted or exchanged in relation to the outcome. PMID- 22075488 TI - Telemedicine enhances quality of forced spirometry in primary care. AB - Forced spirometry is pivotal for diagnosis and management of respiratory diseases, but its use in primary care is suboptimal. The aim of the present study was to assess a web-based application aiming at fostering high-quality spirometry in primary care. This was a randomised controlled trial with 12 intervention primary care units (PCi) and six control units (PCc) studied over 12 months. All 34 naive nurses (PCi and PCc) received identical training. The PCi units had access to educational material and remote expert support. Quality of spirometry and usability of the web application were assessed. We included 4,581 patients (3,383 PCi and 1,198 PCc). At baseline, quality was similar (PCi 71% and PCc 67% high-quality tests). During the study, PCi showed higher percentage (71.5%) of high-quality tests than PCc (59.5%) (p<0.0001). PCi had 73% more chance of high quality performance than PCc. The web application was better for assessing quality of testing than the automatic feedback provided by the spirometer. Healthcare professionals' satisfaction and usability were high. The web-based remote support for primary care by specialists generated a sustained positive impact on quality of testing. The study expands the potential of primary care for diagnosis and management of patients with pulmonary diseases. PMID- 22075489 TI - Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology. AB - Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of <= 8), urea >= 7 mol . L(-1), respiratory rate >= 30 breaths . min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age >= 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol . L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies. PMID- 22075490 TI - Chemoradiotherapy alone as the standard treatment of epidermoid esophageal carcinoma. AB - OBJECTIVES: Surgery has traditionally been the treatment of choice for patients with potentially resectable esophageal carcinoma. Recently, however, definitive chemoradiotherapy (CRT) has been suggested as a preferred treatment modality. In this study, CRT results with or without surgery are compared. METHODS: A total of 986 patients of esophageal carcinoma were categorized into two groups depending on the treatment: surgery (675 patients) or CRT (311 patients). These two groups were compared based on age, sex, weight loss, tumor location and length, tumor shape, grade, stage, delay in receiving treatment, event-free survival (EFS) and overall survival (OS). RESULTS: Patients in the CRT arm were significantly older (p = 0.01), had a more significant adenocarcinoma histology (p = 0.015), upper esophageal carcinoma (p = 0.0001) and more advanced stages of the disease (p = 0.0001). The median EFS for the surgery group was 24.5 months [95% confidence interval (CI), 17-32] versus 22.5 months (95% CI, 16.7-28.2) for the CRT arm (p = 0.56). The mean OS was 59.25 months (95% CI, 53.8-64.7) for the surgery group compared to 58.77 months (95% CI, 50.9-66.6) for the CRT group (p = 0.78). CONCLUSION: Definitive CRT is effective enough so as to consider omitting surgery and could be used as a standard treatment for patients with esophageal carcinoma. PMID- 22075491 TI - [Quo vadis, particle therapy?]. PMID- 22075492 TI - gamma-Glutamylcysteine inhibits oxidative stress in human endothelial cells. AB - AIMS: gamma-Glutamylcysteine (GGC) is a dipeptide and substrate for synthesis of the antioxidant glutathione (GSH), whose health promoting properties include reducing risks of oxidative stress-related injuries and diseases. The objective of this study was to investigate the efficacy of GGC on GSH synthesis and oxidative stress in human endothelial cells. MAIN METHODS: We assessed oxidative stress, GSH, GSH synthetase (GSS) expression, and transcription factor DNA binding levels in human umbilical vein endothelial cells (HUVEC). KEY FINDINGS: We found significantly higher levels of PPARgamma DNA binding and lower levels of GSH, GSS protein, NF-kappaB p65 DNA binding, thiobarbituric acid reactive substances (TBARS), and 8-epi-PGF(2alpha) in a concentration-dependent manner, compared with the control. GSH and GSS protein levels showed a negative correlation with PPARgamma DNA binding levels and positive correlation trends with NF-kappaB p65 DNA binding, TBARS, and 8-epi-PGF(2alpha) levels. A putative binding site for NF-kappaB was found at 4 227 bases upstream from the transcription start site of GSS gene, but none for PPARs. These findings suggest the involvement of NF-kappaB in regulation of GSS expression. Subsequent GSH synthesis might be affected by the suppression of GSS expression in tested conditions. SIGNIFICANCE: Besides its substrate role in GSH synthesis, GGC may play a role in protection against oxidative stress by serving as an antioxidant and modulating the expression of protein(s) related to antioxidant defense. Thus, we speculate that GGC may serve as a novel intra- and intercellular therapeutic dipeptide for oxidative stress-related injuries and diseases. PMID- 22075493 TI - Effect of Pyeongwee-San (KMP6) on 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. AB - AIMS: Recently, some studies reported that digestive tract disease is closely associated with atopic dermatitis (AD). Pyeongwee-San (KMP6) is a Korean medicine, which has come onto the drugstore for the treatment of digestive tract disease. The aim of the present study was to examine whether KMP6 could suppress 2,4-dinitrofluorobenzene (DNFB)-induced AD-like skin lesions in NC/Nga mice. MAIN METHODS: Mice were sensitized with DNFB by applying to shaved dorsal skin. At that time, the drugs or saline were orally administrated to DNFB-applied mice. KEY FINDINGS: The administration of KMP6 or glycyrrhizic acid (GL), a major component of KMP6, inhibited the scratching number in DNFB-induced AD model. The mRNA expressions of interleukin (IL)-4, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and CCR3 were upregulated by DNFB sensitization, but the upregulated mRNA expressions were significantly reduced by the administration of KMP6 or GL. In addition, the levels of IgE, histamine, and IL-4 were significantly reduced by the administration of KMP6 or GL in serum of DNFB induced AD model. However, the level of IFN-gamma in serum was significantly increased by KMP6 or GL. KMP6 or GL also significantly inhibited the numbers of inflammatory cells, mast cells, and protein level of IL-4 in lesions of DNFB induced AD model. Finally, KMP6 or GL significantly decreased the productions of IL-4, IFN-gamma, and TNF-alpha in anti-CD3 plus anti-CD28 antibody-stimulated splenocytes. SIGNIFICANCE: KMP6 showed anti-atopic potential in this setting; hence we suggest it as a potential prospect for anti-atopic agent besides being just a medicine for the stomach and bowels. PMID- 22075494 TI - 3-Bromo-7-nitroindazole attenuates brain ischemic injury in diabetic stroke via inhibition of endoplasmic reticulum stress pathway involving CHOP. AB - AIMS: The role of nitric oxide (NO) and endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of cerebral ischemic/reperfusion (I/R) injury and diabetes. The aim of the study was to investigate the neuroprotective potential of 3-bromo-7-nitroindazole (3-BNI), a potent and selective neuronal nitric oxide synthase (nNOS) inhibitor against ER stress and focal cerebral I/R injury associated with comorbid type 2 diabetes in-vivo. MAIN METHODS: Type 2 diabetes was induced by feeding high-fat diet and streptozotocin (35 mg/kg) treatment in rats. Focal cerebral ischemia was induced by 2h middle cerebral artery occlusion (MCAO) followed by 22 h of reperfusion. Immunohistochemistry and western blotting methods were employed for the detection and expression of ER stress/apoptosis markers [78 kDa glucose regulated protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)]. TUNEL assay for DNA fragmentation was also performed. KEY FINDINGS: The diabetic rats subjected to cerebral I/R had prominent neurological damage and functional deficits compared with sham-operated rats. Massive DNA fragmentation was observed in ischemic penumbral region of diabetic brains. Concomitantly, the enhanced immunoreactivity and expression of ER stress/apoptosis markers were noticed. 3-BNI (30 mg/kg, i.p.) treatment significantly inhibited the cerebral infarct, edema volume and improved functional recovery of neurological deficits. The neuroprotection was further evident by lesser DNA fragmentation with a concomitant reduction of GRP78 and CHOP. SIGNIFICANCE: The study demonstrates the neuroprotective potential of 3 BNI in diabetic stroke model which may be partly due to inhibition of ER stress pathway involving CHOP. PMID- 22075495 TI - The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion. AB - AIMS: The aim of present study was to investigate the effects of isosteviol on hyperglycemia and hyperlipidemia in rats fed with high-fat emulsion (HFE). MAIN METHODS: Hyperglycemia and hyperlipidemia in rats was induced by daily ingestion of HFE for 14 days. Isosteviol (0.2, 1.0, or 5.0mg/kg/day) was orally administered for 7 days, with rosiglitazone maleate (5.0mg/kg/day) used as the positive control. The levels of fasting serum glucose (FSG), fasting serum insulin (FSI), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL) in serum were assayed. Intravenous glucose tolerance test (IVGTT) was performed with serum glucose and insulin levels monitored. The effect of the supplement of palmitate in HFE on the activity of isosteviol was investigated. Ultrastructural changes in islet beta cells and peroxisome proliferator-activated receptor alpha (PPARalpha) mRNA expression profile were determined. KEY FINDINGS: FSG, FSI, TC and LDL levels and insulin resistance index (IRI) were decreased and HDL level was increased by all doses of isosteviol. During IVGTT, serum glucose levels were decreased by isosteviol and no significant differences were observed in insulin release between isosteviol-treated and control groups. The effects of isosteviol were attenuated by palmitate. Damage to pancreatic islet cells was partially attenuated, and expression profile of hepatic PPARalpha mRNA was enhanced by isosteviol. SIGNIFICANCE: Antihyperglycemic effects of isosteviol could enhance utilization of glucose in the periphery and reduce beta-cell damage induced by dyslipidemia. Modulating-lipidemic effects of isosteviol might be related to the potential enhancement of liver PPARalpha mRNA expression. PMID- 22075496 TI - 2011--another successful year for the diabetes educator. PMID- 22075497 TI - A year of achievement ushers in a new era for diabetes care. PMID- 22075500 TI - The educator's guide to diabetes resources, 2011. PMID- 22075501 TI - Exploring the cost and clinical outcomes of integrating the registered nurse certified diabetes educator into the patient-centered medical home. AB - PURPOSE: The purpose of this study was to implement and evaluate a care delivery model integrating the registered nurse-certified diabetes educator into the patient-centered medical home to assist in achieving positive clinical and cost outcomes in diabetes care. METHODS: A 1-group pretest-posttest research design was used. Patients were recruited from 2 patient-centered medical home designated/nominated primary care offices. Inclusion criteria were as follows: diagnosis of type 1 or type 2 diabetes, aged 18 to 80 years, A1C >= 8%, English speaking, and no diabetes education within 6 months. There were 34 participants (men, n = 22; women, n = 12) with a mean age of 53.24. The intervention incorporated an assessment, 4 patient-centered monthly group sessions, and 4 individual follow-up sessions. Study measures included program surveys, participation and satisfaction rates, Healthcare Effectiveness Data and Information Set attainment rates, and the following physiologic measures obtained from the medical record: A1C, fasting blood glucose, LDL, urine microalbumin, blood pressure, retinal eye exam, and body mass index. Cost-effectiveness measures included program costs, performance incentives, revenue, provider time saved, and patient health care utilization. RESULTS: Paired-samples t tests identified significant improvements in A1C, fasting blood glucose, and LDL. Patients and providers were highly satisfied with the program. Cost-benefit analysis revealed a net pretax program benefit. CONCLUSIONS: Results of the study indicated that integrating the registered nurse-certified diabetes educator in the patient-centered medical home improves clinical outcomes and is cost effective. Diabetes education and support are integral components of diabetes management. PMID- 22075502 TI - Algorithmic and consultative integration of transfusion medicine and coagulation: a personalized medicine approach with reduced blood component utilization. AB - BACKGROUND: Therapy customized for the individual patient defines personalized medicine. Current transfusion therapy is performed primarily using general guidelines such as keeping the platelet count at >100,000/MUL, the INR at <= 1.7 and fibrinogen at >100mg/dL for patients undergoing surgery. OBJECTIVE: The purpose of this report is to provide an algorithmic and consultative approach for the delivery of personalized and targeted blood component, blood derivative, and recombinant therapies in order to minimize unnecessary exposure to such therapies and to deliver an optimal risk-benefit ratio for a particular patient. METHODS: The initiative involved a step-wise process that included: 1. establishing "triggers" to alert and permit the clinical pathologist to intervene in the utilization of blood components for a given patient in the context of the blood bank inventory; 2. developing algorithms for the assessment of the patient's procoagulant/anticoagulant status so that appropriate blood component, derivative, and/or recombinant therapies could be instituted while minimizing the risk of thrombophilia; 3. a real time assessment and interpretation of the coagulation data so that dialogue between the pathologist and the patient's clinical team could be effected 24 hours a day, 7 days a week; and 4. monitoring the outcome of these efforts by comparing blood component utilization prior to or during development, early implementation and following full implementation of the program. RESULTS: "Triggers" (i.e., administration of six units of fresh frozen plasma [FFP] or ten units of cryoprecipitate or two single donor [apheresis] platelets in a 24-hour period) were approved. A diagnostic and therapeutic algorithm was constructed, with multidisciplinary input to assist in defining the coagulopathy contributing to the patient's microvascular bleeding in the adult cardiac surgery/cardiac intensive care unit (CICU) and the adult intensive care unit (AICU). Monitoring of utilization, prior to or during development, early implementation and following full implementation of this initiative, revealed a decline in the number of units of FFP, cryoprecipitate and single donor (apheresis) platelets administered. CONCLUSION: We report on the successful development of a model - based on the algorithmic and consultative integration of transfusion medicine and coagulation - that customizes blood component, derivative, and recombinant therapies appropriate for an individual patient's need, resulting in targeted transfusion therapy and associated with reduced blood component utilization. PMID- 22075503 TI - Expression of E-cadherin and beta-catenin in two cholangiocarcinoma cell lines (OZ and HuCCT1) with different degree of invasiveness of the primary tumor. AB - BACKGROUND: Cholangiocarcinoma (CC) is the most frequent malignant epithelial tumor of the biliary system. CC has received increasing interest due to its different etiologic factors, invasiveness, and the difficulty of diagnosis at an early stage. The pathogenesis of CC has not been clearly defined, but cohesiveness of tumor cells seems to be a critical factor. Calcium-dependent adherence proteins or cadherins are a family of proteins essential for connecting the plasma membrane of adjacent cells. Linkage of cadherins with the cytoskeleton occurs through another class of proteins, called catenins. E-cadherin forms a mutually exclusive complex or unit with beta-catenin. Loss of E-cadherin -beta catenin adhesion represents an important step in the progression of many epithelial malignancies. Cell lines arising from CC are not often investigated and may show a differential expression of cell adhesion molecules, particularly E cadherin - beta-catenin. We hypothesized that a moderately invasive cell line of CC may co-localize both molecules in cytoplasm and cytoplasmic membrane, indicating a greater "tightness" of the tumor cells, while a metastasizing cell line may show isolated cytoplasmic membrane localization, indicating tumor cells probably more keen to reach the blood stream and give metastases. Thus, our aim was to investigate the expression and localization of E-cadherin and beta-catenin in two CC cell lines, including a rapidly metastasizing cell line and a moderately invasive cell line, correlating to a different degree of invasiveness of the primary tumor. MATERIALS AND METHODS: OZ and HuCCT1 cells represent homogeneous, functional human biliary epithelial tumor cell lines that were originally isolated in Japan. Following cell line growth we extracted total proteins. Western blot analysis, immunofluorescence and confocal laser microscopy were used to identify the protein expression and their cyto-localization and co localization. RESULTS: Both CC cell lines expressed E-cadherin and beta-catenin, but they showed remarkably different localization patterns. In HuCCT1, both E cadherin and beta-catenin were localized in the cytoplasm, while in OZ these proteins were localized in the cytoplasmic membrane only. This was attributed to a different degree of invasiveness of the primitive CC from which the cell lines were characterized, OZ being a metastasizing cell line, HuCCT1 being a moderately invasive cell line. CONCLUSION: To the best of our knowledge, this is the first time that E-cadherin and beta-catenin have been studied in detail in these two cell lines. These data seem to be very promising in terms of adding insight into the cell biology of CC and initiating investigations that aim to identify cytoskeletal dynamics and ultimately provide guidelines for developing new therapeutic strategies. PMID- 22075504 TI - Relationships of Fetal-Type Erythropoiesis versus Nitric Oxide Production and Glycated Hemoglobin Levels in Diabetics. AB - This study investigated the potential contribution of nitric oxide (NOx) production to enhanced fetal hemoglobin (HbF) synthesis in patients with diabetes. Glycated hemoglobin (HbA1c), HbF, high sensitivity C-reactive protein (hsCRP), plasma glucose levels, and serum NOx concentrations were measured in 350 diabetics and 125 healthy subjects. There were no significant correlations between HbF and HbA1c levels, nor between HbF and plasma glucose levels. However, serum NOx concentrations in patients with HbF >1.0% (76.2 +/- 32.4 MUmol/L) were significantly higher than those with HbF <= 1.0% (47.3 +/- 29.8 MUmol/L, p <0.05). Inversely, patients with moderately increased serum NOx levels >98.1 MUmol/L (75th percentile of patients) exhibited significantly higher HbF levels than those with decreased serum NOx levels <34.2 MUmol/L (25th percentile of patients) (1.16 +/- 0.41 vs. 0.62 +/- 0.28%, p <0.05). After excluding the subjects with high NOx levels, elevated HbF concentrations returned to a level not significantly different from the control value. Serum NOx concentrations were significantly correlated with HbF (r = 0.32, p <0.05) and hsCRP levels (r = 0.35, p <0.05) in diabetic patients. In conclusion, long-term glycemic control does not contribute to fetal-type erythropoiesis, but increased NOx production seems to play an important role in the enhanced HbF synthesis of diabetics. PMID- 22075505 TI - The effect of CYP2C9, VKORC1 genotypes and old age on warfarin pharmacologic sensitivity in korean patients with thromboembolic disease. AB - The therapeutic dose of warfarin is dependent upon intrinsic patient characteristics that are highly variable. We assessed the effects of CYP2C9, VKORC1 1173 C/T polymorphisms, and old age on warfarin dosing and sensitivity by measuring plasma S-/R-warfarin levels in Korean patients. INR and the plasma S-/R warfarin concentrations were determined in 58 patients who had the VKORC1 1173C/T CYP2C9 genotypes, were on a long-term anticoagulation regimen with warfarin, and took a daily dose of warfarin. The pharmacokinetic sensitivity of warfarin was significantly higher in the CYP2C9 *1/*3 genotypes than in the CYP2C9 *1/*1 genotypes [ratio of S-warfarin concentration/dose, 0.53 vs. 0.21; p=0.01]. Pharmacodynamic sensitivity in older patients (>= 75 years) with the CYP2C9 *1/*1 and VKORC1 1173 TT genotypes was significantly higher as compared to younger patients (<75 years) [Ratio of INR/S-warfarin concentration, 4.88 vs. 3.41; p = 0.026]. The CYP2C9*3 allele and old age (>= 75 years) with the VKORC1 1173 T allele were also associated with increased risk of over-anticoagulation. The increase of over-anticoagulation risk and warfarin sensitivity is related to the CYP2C9*3 allele and old age with the VKORC1 1173 T allele in Korean patients with thromboembolic disease. These findings suggest that a lower initial and maintenance dose should be considered for the patients with CYP2C9 *3 allele and advanced age in this patient population. However, due to the limited number of patients in the study population, our finding needs to be confirmed by a larger, well-controlled study. PMID- 22075506 TI - Anti-oxidative effect of apocynin on insulin resistance in high-fat diet mice. AB - The present study examines the effects of apocynin on oxidative stress and antioxidant enzymes in high-fat diet (HFD) induced obese mice. After 12 weeks on HFD, the C57BL/6J mice that clearly exhibited insulin resistance received apocynin (2.4g/L) in their drinking water for five weeks. The results show that apocynin treatment significantly ameliorated hyperglycemia, hyperinsulinemia and dyslipidemia in HFD mice. Furthermore, the intraperitoneal glucose tolerance test (IPGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) indicate significant improvement of insulin sensitivity in HFD mice after apocynin treatment. Compared to the HFD control mice, serum malondialdehyde (MDA) was significantly lower and serum superoxide dismutase (SOD) was significantly higher in apocynin treated HFD mice, indicating that apocynin suppressed systemic oxidative stress in the treated group. In the liver, apocynin significantly reduced the level of MDA. Accordingly, apocynin treatment strengthened the antioxidative defense system with an increased activity of SOD, glutathione peroxidase (GSHpx) and content of reduced glutathione (GSH). We also found that hepatic catalase (CAT) activity significantly decreased after apocynin treatment which may indicate that apocynin reduces hydrogen peroxide and oxidative stress in the liver. These results suggest that apocynin may ameliorate insulin resistance by reducing systemic and hepatic oxidative stress in HFD fed mice. PMID- 22075507 TI - Inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway attenuates cerebral vasospasm following experimental subarachnoid hemorrhage in rabbits. AB - The p38 mitogen-activated protein kinase (MAPK) plays an important role in apoptosis and is also involved in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH). Here, we sought to examine whether inhibition of p38 MAPK could attenuate cerebral vasospasm and investigate the underlying mechanisms in a rabbit SAH model. SAH was established in rabbits (n=12/group) using the double-hemorrhage method. We observed apparent vasospasm in the basilar arteries of rabbits with SAH, which was significantly attenuated by SB203580, a selective p38MAPK inhibitor. Immunoblotting assays showed enhanced phosphorylation of p38 MAPK and ATF2 and increased caspase-3 cleavage following SAH, which were, however, markedly suppressed by SB203580. TUNEL staining further revealed significant apoptosis in the basilar arteries of rabbits with SAH, which was scantly present in rabbits treated with SB203580. Our results demonstrated that p38 MAPK was activated in cerebral vasospasm and associated with increased apoptosis in the basilar arteries and p38 MAPK inhibition suppressed apoptosis, suggesting that p38 MAPK could be a novel therapeutic target for cerebral vasospasm. PMID- 22075508 TI - Comparative analysis of simulated candidemia using two different blood culture systems and the rapid identification of Candida albicans. AB - The goal of this study was to determine the time to detection of Candida species isolates using the two most commonly used automated blood culture systems, and to evaluate rapid, widely available methods for the presumptive identification of C. albicans. Candidemia models of eight commonly detected Candida species were prepared using ATCC standards. The times to detection were evaluated using the BACTEC 9240 (Becton Dickinson) and BacT/Alert 3D (bioMerieux) automated blood culture systems. The presence of pseudohyphae clusters was examined by Gram staining and wet preparation. Germ tube tests were performed directly from blood culture bottles. All samples were cultured on blood agar plates and macroscopically examined for the presence of an irregular margin (spiking). Most Candida species (6/8) except C. glabrata and C. krusei grew more rapidly in aerobic than in anaerobic conditions. Clusters of pseudohyphae were observed in cultures of C. albicans and C. tropicalis. All culture bottles positive for C. albicans were positive by the germ tube test and macroscopically showed 'spiking.' Aerobic and anaerobic blood culture systems can effectively detect candidemia. Furthermore, the direct germ tube test may be the most useful available morphological presumptive identification method for C. albicans. PMID- 22075509 TI - Angiocentric glioma with high proliferative index: case report and review of the literature. AB - With less than 50 cases previously reported in literature, angiocentric glioma (AG) is an uncommon, slow-growing tumor of the CNS that typically exhibits a low proliferative rate and is generally surgically curable. We report the case of a 3 year-old child who presented with seizures and was found to have a non-enhancing parietal lobe lesion with overlying calvarial remodeling. Following complete resection of the tumor, histopathological examination revealed bipolar spindle cells centered on cortical blood vessels, forming pseudorosettes with an ependymomatous appearance. Tumor cells were glial fibrillary acidic protein (GFAP) positive, yet failed to label with synaptophysin. Scattered tumor cells had a "dot-like" cytoplasmic staining with the antibody against epithelial membrane antigen (EMA). Collectively, these features favored a diagnosis of AG. Interestingly, the monoclonal antibody against Ki-67 (MIB-1) labeling rate averaged approximately 10.0%. The child continues to be tumor- and seizure-free ten months postoperatively. Long-term follow up is required to determine if the high proliferative rate observed in this AG translates into altered clinical behavior and/or a worse prognosis. PMID- 22075510 TI - Intravascular large B-cell lymphoma presenting as cholecystitis and pancytopenia: case report with literature review. AB - Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of extranodal diffuse large Bcell lymphoma with only a few more than 300 cases reported. It is characterized as lymphoma cells confined to the lumina of small vessels, so patients usually do not present with masses or lymphadenopathy. Clinical presentations of these patients are non-specific and the pathologic changes may be subtle, which often leads to delayed diagnoses and, in many instances, a postmortem diagnosis. IVLBCL can essentially involve the vessels of any organ, but it is quite rare for the gallbladder to serve as the initial presenting site; there are only four such cases reported in the English literature. Furthermore, IVLBCL of the gallbladder with peripheral blood involvement is even less common. We report a recent case of IVLBCL presenting as acute cholecystitis and pancytopenia. The patient underwent a simple cholecystectomy. Examination of the gallbladder showed clusters of large lymphoma cells within lumina of small vessels in the gallbladder wall. These cells were positive for CD5/CD20 and negative for CD3, CD10, and TdT. Based on these findings, a diagnosis of IVLBCL was made. Coincidently, circulating lymphoma cells were identified in the peripheral blood and confirmed by flow cytometric analysis (positive for CD19/CD20/CD5, without light chain expression). The patient was started on chemotherapy but subsequently died of chemotherapy related multi-organ failure 10 days after the initial diagnosis. PMID- 22075511 TI - T-cell acute lymphoblastic leukemia associated with complex karyotype and SET NUP214 rearrangement: a case study and review of the literature. AB - SET-NUP214 rearrangements have been rarely reported in T-cell acute lymphoblastic leukemia (T-ALL), acute undifferentiated leukemia, and acute myeloid leukemia, and most documented cases have been associated with normal karyotypes in conventional cytogenetic analyses. Here, we describe a novel case of T-ALL associated with a mediastinal mass and a SET-NUP214 rearrangement, which was masked by a complex karyotype at the time of initial diagnosis. Using multiplex reverse transcriptase-polymerase chain reaction analysis, we detected a cryptic SET-NUP214 rearrangement in our patient. As only 11 cases (including the present study) of T-ALL with SET-NUP214 rearrangement have been reported, the clinical features and treatment outcomes have not been fully determined. Further studies are necessary to evaluate the incidence of SET-NUP214 rearrangement in T-ALL patients and the treatment responses as well as prognosis of these patients. PMID- 22075512 TI - A novel homozygous missense ADAMTS13 mutation Y658C in a patient with recurrent thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenic purpura (TTP) is a devastating systemic disorder that is characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurological dysfunction, and renal failure. In the hereditary form of TTP, severe deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor, is associated with the development of this disorder. A 34-year old woman was diagnosed with TTP due to severely reduced ADAMTS13 activity; clinical manifestations resolved only by repeated total plasma exchanges or transfusion. Homozygous and heterozygous Y658C (c.1973A>G) alleles were detected in the patient and her child with severe and mild ADAMTS13 deficiencies, respectively. Herein, we report a novel missense mutation Y658C (c.1973A>G) on exon 17 of ADAMTS13 and discuss its clinical implications. PMID- 22075513 TI - Primary Plasma Cell Leukemia Associated with t(6;14)(p21;q32) and IGH Rearrangement: A Case Study and Review of the Literature. AB - Because plasma cell leukemia (PCL) is a rare and distinct variant among plasma cell dyscrasias, recent clinical and cytogenetic studies have been performed in different ethnic groups to define the characteristics of these PCL patients. As far as we know, IGH rearrangements involving t(11;14) and (14;16) are significantly more frequent in PCL than in myeloma patients. However, PCL cases associated with t(6;14)(p21;q32) or IGH-CCND3 rearrangement are extremely rare in the literature; only one PCL case with t(6;14) has been documented. A 61-year-old female was admitted due to fatigue, weight loss, and exertional dyspnea. Plasmacytoid cells were counted up to 76% at a peripheral blood film, but bone marrow aspiration failed because of dry-tapping. Flow cytometric analysis showed positive for CD138 and cytoplasmic kappa light chain. Chromosome analysis revealed t(6;14)(p21;q32), which was confirmed by an IGH split-out probe in FISH analysis. Immunofixation electrophoresis also presented monoclonal bands identified as IgG and kappa light chain. Finally, she was diagnosed as primary PCL associated with t(6;14) and IGH rearrangement. Although considerable advances have been made in the understanding of the biology and molecular pathogenesis of PCL, further clinical, laboratory, and genetic studies of PCL associated with such a rare IGH rearrangement would be necessary in the future. To the best of our knowledge, this is the first report of PCL associated with t(6;14) as a sole chromosomal abnormality. PMID- 22075514 TI - A novel a subtype allele that demonstrates allelic competition. AB - A 68-year-old man with an ABO discrepancy discovered during a routine check up and 3 members of his family were referred for ABO analysis. A novel allele (A(w)14; 699 C>A, H233Q) was found by sequence analysis of exons 6&7 and in those with the A(w)14 allele, complete ABO analysis was performed. The propositus and his son had an A(w) phenotype with the A(w)14/O01 genotype. His daughter had an A(w)14/B101 genotype with a normal B phenotype. Three-dimensional molecular modelling was used to predict the effect of the H233Q amino acid change on the resulting A glycosyltransferase. The A(w)14 produced a weak A phenotype, and its ability to produce A antigens was further reduced when it was co-inherited with a B101 enzyme. PMID- 22075515 TI - BizarreParosteal Osteochondromatous Proliferation (Nora's lesion) with translocation t(1;17)(q32;q21): a case report and role of cytogenetic studies on diagnosis. AB - Bizarre Parosteal Osteochondromatous Proliferation (BPOP) is a benign tumor-like lesion that has recently been reported to have an association with a specific translocation t(1:17)(q32;q21)[1]. Like other reactive periosteal lesions, BPOP can be diagnostically challenging, with the ever-present possibility of a potentially devastating erroneous diagnosis of malignancy. These lesions are often clinically, radiologically and histopathologically ambiguous, with rapid but circumscribed, non-infiltrative growth patterns, and histological atypia, but without overt features of malignancy. However, recent published reports have better characterized radiological [2] as well as histological features that aid in making an accurate diagnosis. In spite of all these advances, one of the biggest challenges in making the correct diagnosis still remains the inexperience of the practicing pathologist with this lesion, simply due to its rarity. We present a case of Nora's lesion in the distal ulna of an 8 year-old girl, in which, besides the histological features, we were able to demonstrate the translocation t(1:17)(q32;q21). Thus, we would like to emphasize the utility of cytogenetic studies in the correct and rapid diagnosis of clinically and radiologically ambiguous periosteal-based lesion. PMID- 22075516 TI - Peri-appendiceal inflammation in an 8-year-old child with chronic ulcerative colitis. AB - The peri-appendiceal red patch (PARP) or appendiceal orifice inflammation (AOI) is a known complication of non-pancolonic ulcerative colitis (UC), but it is not well documented in the pediatric pathology and gastroenterology literature. Here we describe the youngest patient with this manifestation to date and provide a brief review on PARP associated UC. PMID- 22075518 TI - Brain. Editorial. PMID- 22075520 TI - The proliferative capacity of the subventricular zone is maintained in the parkinsonian brain. AB - There are many indications that neurogenesis is impaired in Parkinson's disease, which might be due to a lack of dopamine in the subventricular zone. An impairment in neurogenesis may have negative consequences for the development of new therapeutic approaches in Parkinson's disease, as neural stem cells are a potential source for endogenous repair. In this study, we examined the subventricular zone of 10 patients with Parkinson's disease and 10 age- and sex matched controls for proliferation and neural stem cell numbers. We also included five cases with incidental Lewy body disease, which showed Parkinson's disease pathology but no clinical symptoms and thus did not receive dopaminergic treatment. We quantified the neural stem cell number and proliferative capacity in the subventricular zone of these three donor groups. We found subventricular neural stem cells in each donor, with a high variation in number. We did not observe significant differences in neural stem cell number or in proliferation between the groups. Additionally, we were able to culture neural stem cells from post-mortem brain of several patients with Parkinson's disease, confirming the presence of viable neural stem cells in these brains. We have also examined the subventricular zone of a chronic, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson's disease mouse model, and again found no effect of dopaminergic denervation on precursor proliferation. Lastly, we investigated the proliferation capacity of two different human neural stem cell lines in response to dopamine. Both cell lines did not respond with a change in proliferation to treatment with dopamine agonists and an antagonist. In summary, the adult neural stem cell pool in the subventricular zone was not clearly affected in the human parkinsonian brain or a Parkinson's disease mouse model. Furthermore, we did not find evidence that dopamine has a direct effect on human neural stem cell proliferation in vitro. Thus, we conclude that the number of adult neural stem cells is probably not diminished in the parkinsonian brain and that dopamine depletion most likely has no effect on human neural stem cells. PMID- 22075519 TI - Can loss of muscle spindle afferents explain the ataxic gait in Riley-Day syndrome? AB - The Riley-Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10-30 uA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains their loss of deep tendon reflexes. Moreover, we suggest that their ataxic gait is sensory in origin, due to the loss of functional muscle spindles and hence a compromised sensorimotor control of locomotion. PMID- 22075521 TI - Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease. AB - Parkinson's disease is a relentlessly progressive neurodegenerative disease. Breakdown of compensatory mechanisms influencing putaminal dopamine processing could contribute to the progressive motor symptoms. We studied a cohort of 78 subjects (at baseline) with sporadic Parkinson's disease and 35 healthy controls with multi-tracer positron emission tomography scans to investigate the evolution of adaptive mechanisms influencing striatal dopamine processing in Parkinson's disease progression. Presynaptic dopaminergic integrity was assessed with three radioligands: (i) [(11)C](+/-)dihydrotetrabenazine, to estimate the density of vesicular monoamine transporter type 2; (ii) [(11)C]d-threo-methylphenidate, to label the dopamine transporter; and (iii) 6-[(18)F]fluoro-L-DOPA, to assess the activity of aromatic amino acid decarboxylase and storage of 6-[(18)F] fluorodopamine in synaptic vesicles. The subjects with Parkinson's disease and the healthy controls underwent positron emission tomography scans at the initial visit and after 4 and 8 years of follow-up. Non-linear multivariate regression analyses with random effects were utilized to model the longitudinal changes in tracer values in the putamen standardized relative to normal controls. We found evidence for possible upregulation of dopamine synthesis and downregulation of dopamine transporter in the more severely affected putamen in the early stage of Parkinson's disease. The standardized 6-[(18)F]fluoro-L-DOPA and [(11)C]d-threo methylphenidate values tended to approach [(11)C](+/-)dihydrotetrabenazine values in the putamen in later stages of disease (i.e. for [(11)C](+/ )dihydrotetrabenazine values <25% of normal), when the rates of decline in the positron emission tomography measurements were similar for all the markers. Our data suggest that compensatory mechanisms decline as Parkinson's disease progresses. This breakdown of compensatory strategies in the putamen could contribute to the progression of motor symptoms in advanced disease. PMID- 22075522 TI - Resolution of spatial and temporal visual attention in infants with fragile X syndrome. AB - Fragile X syndrome is the most common cause of inherited intellectual impairment and the most common single-gene cause of autism. Individuals with fragile X syndrome present with a neurobehavioural phenotype that includes selective deficits in spatiotemporal visual perception associated with neural processing in frontal-parietal networks of the brain. The goal of the current study was to examine whether reduced resolution of spatial and/or temporal visual attention may underlie perceptual deficits related to fragile X syndrome. Eye tracking was used to psychophysically measure the limits of spatial and temporal attention in infants with fragile X syndrome and age-matched neurotypically developing infants. Results from these experiments revealed that infants with fragile X syndrome experience drastically reduced resolution of temporal attention in a genetic dose-sensitive manner, but have a spatial resolution of attention that is not impaired. Coarse temporal attention could have significant knock-on effects for the development of perceptual, cognitive and motor abilities in individuals with the disorder. PMID- 22075523 TI - Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study. AB - Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility- Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = 0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 +/- 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 +/- 0.037 SD/SD, P<0.001), grey matter (-0.079 +/- 0.038 SD/SD, P = 0.038) and white matter (-0.128 +/- 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (-0.095 +/- 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 +/- 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 +/- 0.039 SD/SD, P<0.001), slower processing speed (-0.118 +/- 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (-0.155 +/- 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains. PMID- 22075524 TI - Perfusion computer tomography: imaging and clinical validation in acute ischaemic stroke. AB - Computed tomography perfusion imaging in acute stroke requires further validation. We aimed to establish the optimal computed tomography perfusion parameters defining the infarct core and critically hypoperfused tissue. Sub-6-h computed tomography perfusion and 24-h magnetic resonance imaging were analysed from 314 consecutive patients with ischaemic stroke. Diffusion-weighted imaging lesion volume at 24 h was used to define the extent of critically hypoperfused tissue (in patients without reperfusion between acute and 24-h time points), and infarct core (in patients with major reperfusion at 24 h). Pixel-based analysis of co-registered computed tomography perfusion and diffusion-weighted imaging was then used to define the optimum computed tomography perfusion thresholds for critically hypoperfused at-risk tissue and infarct core. These optimized acute computed tomography perfusion threshold-based lesion volumes were then compared with 24-h diffusion-weighted imaging infarct volume, as well as 24-h and 90-day clinical outcomes for validation. Relative delay time >2 s was the most accurate computed tomography perfusion threshold in predicting the extent of critically hypoperfused tissue with both receiver operating curve analysis (area under curve 0.86), and the volumetric validation (mean difference between computed tomography perfusion and 24-h diffusion-weighted imaging lesions = 2 cm(2), 95% confidence interval 0.5-3.2 cm(2)). Cerebral blood flow <40% (of contralateral) within the relative delay time >2 s perfusion lesion was the most accurate computed tomography perfusion threshold at defining infarct core with both receiver operating characteristic analysis (area under curve = 0.85) and the volumetric validation. Using these thresholds, the extent of computed tomography perfusion mismatch tissue (the volume of 'at-risk' tissue between the critically hypoperfused and core thresholds) salvaged from infarction correlated with clinical improvement at 24 h (R(2) = 0.59, P = 0.04) and 90 days (R(2) = 0.42, P = 0.02). Patients with larger baseline computed tomography perfusion infarct core volume (>25 ml) also had poorer recovery at Day 90 (P = 0.039). Computed tomography perfusion can accurately identify critically hypoperfused tissue that progresses to infarction without early reperfusion, and the computed tomography perfusion cerebral blood flow infarct core closely predicts the final volume of infarcted tissue in patients who do reperfuse. The computed tomography perfusion infarct core and at-risk measures identified are also strong predictors of clinical outcome. PMID- 22075525 TI - Inhibition of A. carbonarius growth and reduction of ochratoxin A by bacteria and yeast composites of technological importance in culture media and beverages. AB - Five composites of yeast and six of bacterial isolates from fermented products were studied, in order to assess their ability to inhibit Aspergillus carbonarius growth and reduce OTA concentration in culture media and beverages. The antagonistic effect of the above composites against A. carbonarius growth was studied in synthetic grape medium of pH 3.5 and a(w) 0.98, 0.95, 0.92 after incubation at 25 degrees C. Different combinations of initial inocula of bacteria or yeast composites and fungi were used (10(2)cfu/mL vs 10(5)spores/mL; 10(5)cfu/mL vs 10(2)spores/mL; and 10(5)cfu/mL vs 10(5)spores/mL). Regarding the OTA reduction experiment, 10(3) and 10(7)cfu/mL of the bacteria and yeast composites were inoculated in liquid media of different pH (3.0, 4.0, 5.0, and 6.1 or 6.5) and initial OTA concentration (50 and 100MUg/L) and incubated at 30 degrees C. Moreover, grape juice, red wine, and beer were supplemented with 100MUg/L of OTA and inoculated with composites of 16 yeasts (16YM) and 29 bacterial (29BM) strains (10(7)cfu/mL) to estimate the kinetics of OTA reduction at 25 degrees C for 5days. Fungal inhibition and OTA reduction were calculated in comparison to control samples. None of the bacterial composites inhibited A. carbonarius growth. The high inoculum of yeast composites (10(5) cfu/mL) showed more efficient fungal inhibition compared to cell density of 10(2) cfu/mL. All yeast composites showed higher OTA reduction (up to 65%) compared to bacteria (2 25%), at all studied assays. The maximum OTA reduction was obtained at pH 3.0 by almost all yeast composites. For all studied beverages the decrease in OTA concentration was higher by yeasts (16YM) compared to bacteria (29BM). The highest OTA reduction was observed in grape juice (ca 32%) followed by wine (ca 22%), and beer (ca 12%). The present findings may assist in the control of A. carbonarius growth and OTA production in fermented foodstuffs by the use of proper strains of technological importance. PMID- 22075526 TI - Competencies for the physician medical geneticist in the 21st century. PMID- 22075528 TI - Quality of life in adult survivors of pediatric kidney transplantation. AB - BACKGROUND: There are few studies assessing long-term adult outcome and health related quality of life (HRQOL) in former pediatric high-risk kidney transplant (TX) recipients. METHODS: Twenty-one patients were assessed at mean age of 21.1 years. Mean age at first TX was 2.4 years. Brain arterial border zone infarcts had been documented in 54% of the children. HRQOL was assessed with the general 15-dimensional (15D) instrument generating an index on a 0 and 1 scale (1 for best). The results were compared with the corresponding childhood 17-dimensional instrument and an adult control group from the general population. Psychosocial adjustment was assessed with the ASEBA Adult Self Report (ASR) and compared with the childhood Child Behavior Checklist assessments. RESULTS: Half of the patients (52%) had a secondary level general or vocational education. The educational outcome was evenly distributed (compulsory vs. secondary) regardless of previous childhood brain ischemia. The ASR Total Problems score was in the normal range for all patients. Four patients had scores in the pathological range for Externalizing or Internalizing Problems. There was a correlation between the childhood Child Behavior Checklist problem scores and the adult ASR scores for Internalizing and Total Problems but not for Externalizing Problems. Their mean 15D HRQOL index was 0.94 and lower than for the control group (0.97, P=0.04). There was a strong correlation between the childhood 17-dimensional and the adult 15D HRQOL index (r=0.63, P=0.003). CONCLUSION: The long-term outcome is fair in former high-risk pediatric TX patients with neurological comorbidity. Childhood psychosocial adjustment and HRQOL may predict the outcome in adults. PMID- 22075529 TI - Neuropsychological functioning in patients with alcohol-related liver disease before and after liver transplantation. AB - BACKGROUND: Cognitive dysfunction is common in both end-stage liver disease and chronic alcohol misuse. The impact of orthotopic liver transplantation (OLT) on neuropsychological function is poorly documented. This prospective study examined changes in cognitive function pre- and post-OLT in patients with alcohol-related liver disease (ALD). METHODS: Comprehensive neuropsychological assessment was conducted with 92 abstinent patients with ALD scheduled for OLT. Forty-two patients were available for reassessment 12 months post-OLT. RESULTS: Posttransplantation, cognitive performance on all measures fell within normal limits. Greatest improvement occurred in visuomotor speed, complex visual attention processes, and the ability to solve visually presented problems. Performance on memory assessment tasks also improved posttransplantation. Applying a more robust assessment of change (Reliable Change Index), approximately half improved reliably on overall cognitive function. One quarter improved in memory performance. With the exception of the Full-Scale Intelligence Quotient scales, discriminant analysis was unable to successfully predict which patients reliably improved. CONCLUSIONS: Overall improvement in cognitive function occurs after liver transplantation in ALD. It was not possible to identify which patient characteristics were associated with reliable change. PMID- 22075527 TI - Clinical utility of family history for cancer screening and referral in primary care: a report from the Family Healthware Impact Trial. AB - PURPOSE: To assess the effectiveness of computerized familial risk assessment and tailored messages for identifying individuals for targeted cancer prevention strategies and motivating behavior change. METHODS: We conducted a randomized clinical trial in primary care patients aged 35-65 years using Family Healthware, a self-administered, internet-based tool that collects family history for six common diseases including breast cancer, colon cancer, and ovarian cancer, stratifies risk into three tiers, and provides tailored prevention messages. Cancer screening adherence and consultation were measured at baseline and 6-month follow-up. RESULTS: Of 3283 participants, 34% were at strong or moderate risk of at least one of the cancers. Family Healthware identified additional participants for whom earlier screening (colon cancer, 4.4%; breast cancer, women ages: 35-39 years, 9%) or genetic assessment (colon cancer, 2.5%; breast cancer, 10%; and ovarian cancer, 4%) may be indicated. Fewer than half were already adherent with risk-based screening. Screening adherence improved for all risk categories with no difference between intervention and control groups. Consultation with specialists did not differ between groups. CONCLUSION: Family Healthware identified patients for intensified cancer prevention. Engagement of clinicians and patients, integration with clinical decision support, and inclusion of nonfamilial risk factors may be necessary to achieve the full potential of computerized risk assessment. PMID- 22075530 TI - A possible explanation for anemia in patients treated with mycophenolic acid. AB - BACKGROUND: Clinical studies suggest that the immunosuppressant mycophenolate mofetil is associated with anemia. However, the mechanism for this is not known. Here, we studied the effect of mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil, on erythropoiesis in vitro. METHODS: Both UT-7 cells and primary murine bone marrow cells were studied. Cells were initially treated with erythropoietin and MPA and proliferation and caspase-3 assays were performed. The effect of guanosine-5'-triphosphate, guanosine, and caspase inhibitors was also investigated. RESULTS: MPA was found to decrease the proliferation of UT-7 cells and erythropoiesis in murine bone marrow cells. This inhibition was associated with an increase in caspase-3 activity in the UT-7 cells. Inhibition was reversed in UT-7 cells and in murine bone marrow by guanosine, but not by caspase inhibitors. The apoptosis induced by MPA was also reversed by guanosine. UT-7 cells treated with MPA showed a decreased inosine-5'-monophosphate dehydrogenase activity. CONCLUSION: These results suggest that MPA inhibits inosine-5' monophosphate dehydrogenase activity in erythroid cells and that this is a likely mechanism of action of anemia in MPA-treated patients. PMID- 22075531 TI - Amelioratory effects of testosterone propionate supplement on behavioral, biochemical and morphological parameters in aged rats. AB - Testosterone has been shown to affect motor behavior and nigrostriatal dopaminergic (NSDA) system in young and adult male rats. However, it is not known whether exogenous testosterone intervention to aged male rats can ameliorate age related motor impairment. Thus, in the present study, the open field motor behavior and adhesive tape removal motor performance as well as the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) of NSDA system were examined in aged male rats following chronic subcutaneous injections of testosterone propionate (TP). Aged rats showed significantly reduced open field motor behavior and adhesive tape removal motor performance compared to adult rats. Chronic TP supplement significantly ameliorated the age-related motor deficits. The expression of TH and DAT of NSDA system was significantly enhanced in TP-treated aged rats revealed by RT-PCR, Western blot and immunohistochemistry analysis respectively. The results imply that chronic TP treatment may favorably improve the declined motor behavior and motor performance with aging. Testosterone propionate supplement that facilitated NSDA system may influence the maintenance of motor behavior and performance in aged rats. PMID- 22075532 TI - Effect of fermented Panax ginseng extract (GINST) on oxidative stress and antioxidant activities in major organs of aged rats. AB - The intracellular levels of oxidant and antioxidant balances are gradually distorted during the aging process. An age associated elevation of oxidative stress occurring throughout the lifetime is hypothesized to be the major cause of aging. The present study was undertaken to evaluate the putative antioxidant activity of the fermented Panax ginseng extract (GINST) on lipid peroxidation and antioxidant status of major organs of aged rats compared to young rats. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were observed in the serum of aged rats. Increased levels of malondialdehyde (MDA) and significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were observed in the liver, kidneys, heart and lungs of aged rats, when compared with those in young rats. Quantitative analysis of the non-enzymatic antioxidants such as reduced glutathione (GSH), ascorbic acid and alpha-tocopherol levels showed significantly lower values in the liver, kidneys, heart and lungs of aged rats. On the other hand, administration of the fermented Panax ginseng extract (GINST) to aged rats resulted in increased activities of SOD, CAT, GPx, GR and GST as well as elevation in GSH, ascorbic acid and alpha-tocopherol levels. Besides, the level of MDA, AST, ALT, urea and creatinine were reduced on administration of GINST to aged rats. These results suggested that treatment of GINST can improve the antioxidant status during aging, thereby minimizing the oxidative stress and occurrence of age-related disorders associated with free radicals. PMID- 22075533 TI - Behavioral effects of estradiol therapy in ovariectomized rats depend on the age when the treatment is initiated. AB - Clinical studies suggest that aging may affect the neural outcome of estrogen therapy in postmenopausal women. In this study we have assessed whether age influences the behavioral outcome of estradiol therapy in rats. Animals were ovariectomized at 2 or 20 months of age. Immediately after ovariectomy animals were treated for 10 weeks with estradiol valerate or vehicle. Estradiol therapy decreased body weight in both young and older rats compared to animals injected with vehicle. In contrast, estradiol treatment improved object recognition memory and decreased anxiety-like behavior in the circular open field of older but not young rats and decreased depressive-like behavior of young but not older animals. Thus, our findings indicate that age affects the outcome of estradiol therapy in the brain. PMID- 22075534 TI - Superparamagnetic Fe3O4 nanoparticles-carbon nitride nanotube hybrids for highly efficient peroxidase mimetic catalysts. AB - We report a facile route to synthesize size tunable Fe(3)O(4) nanoparticles (NPs) carbon nitride nanotube (CNNT) hybrids. These hybrids showing the water-soluble property are proven to exhibit ultra high peroxidase mimetic activity compared to those of pure NPs, where a colorless peroxidase substrate 3,3,5,5 tetramethylbenzidine changes by H(2)O(2) to its blue colored oxidized state. PMID- 22075535 TI - Lung cancer and indoor radon exposure in the north of Portugal--an ecological study. AB - BACKGROUND: Indoor radon exposure is a well documented environmental factor as a leading cause of lung cancer. OBJECTIVES: The aim of this study was to assess the risk of lung cancer and estimate the number of deaths due to indoor radon exposure in the north of Portugal, between 1995 and 2004. METHODS: The sixth Biological Effects of Ionizing Radiation Committee (BEIR VI) preferred models were applied to estimate the risk of developing lung cancer induced by indoor radon exposure, by age and level of exposure, and calculated the number of lung cancer deaths attributable to this exposure. Lung cancer mortality data were granted by the North Regional Health Administration and indoor radon concentrations resulted from a national survey conducted by the Portuguese Environmental Agency. The smoking habit was accounted with two methods. A submultiplicative interaction between smoking and indoor radon exposure was considered. RESULTS: Depending on the model applied and the method used to account for the smoking habit, the estimated number of lung cancer deaths attributed to indoor radon exposure, in northern Portugal, ranges from 1565 to 2406, for the period between 1995 and 2004. This indicates that of the 8514 lung cancer deaths observed, from 18 to 28% could be associated with indoor radon exposure. CONCLUSIONS: This was the first study realized in Portugal on the impact of indoor radon exposure in lung cancer mortality. The application of the BEIR VI models led to a high number of lung cancer deaths due to indoor radon exposure. PMID- 22075536 TI - Evaluating the long-term effect of FOBT in colorectal cancer screening. AB - BACKGROUND: Cancer screening has been effective in detecting tumors early before symptoms appear. However, the effectiveness of the regular fecal occult blood test (FOBT) in colorectal cancer in the long term has not been quantified. METHODS: We applied the statistical method developed by Wu and Rosner using data from the Minnesota Colon Cancer Control Study (MCCCS). All initially asymptomatic participants were classified into four mutually exclusive groups: true-early detection, no-early-detection, over-diagnosis, and symptom-free life; human lifetime was treated as a random variable and is subject to competing risks. All participants in the screening program will eventually fall into one of the four outcomes above. Predictive inferences on the percentages of the four outcomes for both genders were made using the Minnesota study data. RESULTS: Depending on gender, screening frequency and age at the initial screening, for all participants the probability of "symptom-free-life" varies between 95.3% and 96.6%; the probability of "true-early-detection" is 1.9-3.8%; the probability of no-early-detection is 0.3-2.0%; the probability of over-diagnosis is 0.16-0.3%. Among those with colorectal cancer detected by regular FOBT, the probability of over-diagnosis is lower than expected and is between 6% and 9%, with 95% CI (2.5%, 21.3%) for females and (1.9%, 44.7%) for males. The probability of true early-detection increases as screening interval decreases. The probability of no early-detection decreases as screening interval decreases. CONCLUSION: The probability of over-diagnosis among the screen-detected cases is not as high as previously thought. We hope this outcome can provide valuable information on the effectiveness of the FOBT in colorectal cancer detection in the long term. PMID- 22075537 TI - Woman with persistent cough. PMID- 22075538 TI - Patients with CD36 deficiency are associated with enhanced atherosclerotic cardiovascular diseases. AB - AIM: The clustering of dyslipidemia, impaired glucose tolerance and hypertension increases the morbidity and mortality from cardiovascular events. A class B scavenger receptor, CD36, is a receptor for oxidized LDL and a transporter of long-chain fatty acids. Because of the impaired uptake of oxidized LDL in CD36 deficient macrophages and from the results of CD36 knockout mice, CD36 deficiency (CD36-D) was supposed to be associated with reduced risks for coronary artery disease (CAD); however, CD36-D patients are often accompanied by a clustering of coronary risk factors. The current study aimed to investigate the morbidity and severity of cardiovascular diseases in CD36-D patients. METHODS: By screening for CD36 antigen on platelets and monocytes using FACS or the absent myocardial accumulation of 123I-BMIPP by scintigraphy, 40 patients with type I CD36-D were collected, the morbidity of CAD and their features of atherosclerotic cardiovascular diseases were observed. Screening for CD36-D in both CAD patients (n = 319) and healthy subjects (n = 1,239) were underwent. RESULTS: The morbidity of CAD was significantly higher in CD36-D patients than in the general population; 50% of patients (20 out of 40) had CAD identified by BMIPP scintigraphy and 37.5% (3 out of 8) by FACS screening, respectively. Three representative CD36-D cases demonstrated severe CAD and atherosclerosis. The frequency of CD36-D was three times higher in CAD patients than in healthy subjects (0.9% vs 0.3%, p < 0.0001). CONCLUSION: The morbidity of CAD is significantly higher in CD36-D patients suffering from severe atherosclerosis, implying that the status of CD36-D might be atherogenic. PMID- 22075539 TI - No association of diabetic duration or insulin use with the prognosis of critical limb ischemia after endovascular therapy. AB - AIM: To examine whether diabetic duration and insulin use are independently associated with the prognosis of critical limb ischemia (CLI) after endovascular therapy. METHODS: We recruited 312 Japanese patients who underwent endovascular therapy for CLI. The outcome measures were major amputation and mortality. Cox proportional hazards regression analyses were performed. RESULTS: The prevalence of diabetes mellitus (DM) was 69%, and 47% of the DM population were treated with insulin. DM patients with insulin use had hemoglobin A1c (HbA1c) of 7.5 +/- 1.3% and diabetic duration of 21 +/- 11 years, whereas those without insulin use had HbA1c of 6.6 +/- 1.4% and diabetic duration of 19 +/- 11 years. Follow-up period was 93 +/- 72 weeks; 55 patients underwent major amputations and 102 died. Diabetic duration and insulin use had significant associations with major amputation in each univariate model, with an unadjusted hazard ratio (HR) and 95% confidence interval (CI) of 1.019 [1.000, 1.039] in one-year increments and 2.321 [1.368, 3.938], respectively. In the multivariate model, however, diabetic duration and insulin use were not significantly associated with limb prognosis, as HbA1c level was, with an adjusted HR [95% CI] of 1.332 [1.114, 1.593] in 1% increment. Mortality had no statistical association with any of these DM-related variables. CONCLUSION: Diabetic duration and insulin use were not independent risk factors for the prognosis of CLI after endovascular therapy. PMID- 22075540 TI - Exposure to particulate matter and long-term risk of cardiovascular mortality in Japan: NIPPON DATA80. AB - AIM: It remains uncertain whether chronic exposure to particulate air pollution is associated with increased mortality in Japan because Japan has a different distribution pattern of cardiovascular disease and its risk factors compared to Western countries. We investigated the association between long-term exposure to particulate matter (PM) and cardiovascular mortality risk using a representative Japanese cohort. METHODS: A total of 7,250 participants aged 30 years and older from 232 districts throughout Japan were followed from 1980 to 2004. We linked the averaged annual concentrations of PM from 1985 to 2004 to each cohort participant who resided in the district at the time of the baseline survey. Study participants were divided into quintiles of average PM concentration. We applied the Cox proportional hazard model adjusting for sex, age, body mass index, blood pressure, total cholesterol, blood glucose, smoking categories, drinking categories, and the municipality population size. RESULTS: During follow-up, there were 1,716 deaths from all causes; 571 from cardiovascular disease, 116 from coronary heart disease, and 250 from stroke. Hazard ratios were not different among the quintiles and those for trend per 10 ug/m3 increase in annual PM concentration were 0.98 (95% confidence interval, 0.92-1.04) for all-cause mortality and 0.90 (95% confidence interval, 0.81-1.00) for cardiovascular mortality. CONCLUSION: Long-term exposure to PM was not associated with increased cardiovascular mortality risk in this population-based cohort in Japan. PMID- 22075541 TI - Proton pump inhibitors versus histamine-2-receptor antagonists for the management of iatrogenic gastric ulcer after endoscopic mucosal resection or endoscopic submucosal dissection: a meta-analysis of randomized trials. AB - BACKGROUND/AIMS: Both proton pump inhibitor (PPI) and histamine-2-receptor antagonist (H(2)RA) are considered to be effective for the treatment of iatrogenic gastric ulcer after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). We aimed to systematically evaluate the evidence comparing PPI and H(2)RA for iatrogenic ulcer. METHODS: Data from PubMed, Cochrane Library and Google Scholar were searched to identify eligible randomized trials. Outcome measures were delayed bleeding, epigastric pain and ulcer healing. RESULTS: Six full-text studies were identified including a total of 522 patients. Pooled data suggested a significantly lower bleeding rate in the PPI group than in the H(2)RA group (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.25-0.95). Subgroup analysis showed PPI was more effective in the prevention of bleeding than H(2)RA for ESD-induced ulcer (OR 0.41, 95% CI 0.20 0.85) and 8-week duration of medication (OR 0.36, 95% CI 0.17-0.76). There were no differences in the incidence of epigastric pain (OR 0.90, 95% CI 0.53-1.51) and ulcer healing rate after endoscopic therapies between both groups. CONCLUSION: This meta-analysis shows PPI is superior to H(2)RA for the prevention of delayed bleeding without different effectiveness in the reduction of epigastric pain and in the promotion of ulcer healing after EMR or ESD. PMID- 22075542 TI - Retinoic acid induces two osteocalcin isoforms and inhibits markers of osteoclast activity in Atlantic cod (Gadus morhua) ex vivo cultured craniofacial tissues. AB - Nutritional status including vitamin A could explain some of the developmental deformities observed in cultivated teleosts, including Atlantic cod (Gadus morhua). In the present study we aimed to investigate the transcriptional effect of retinoic acid (RA) on bone related genes using Atlantic cod craniofacial explants tissue cultures. Two different osteoblast specific osteocalcin/bone gla protein isoforms were discovered in cod. Transcription of both isoforms was up regulated following RA treatment of 65 dph cod lower jaw explants. In contrast, transcripts coding for genes related to bone resorption and osteoclast activity, matrix metalloproteinase 9 and cathepsin K were down-regulated following RA treatment. This could be linked to the decreased transcriptional ratio between receptor activator of nuclear factor kappa-B ligand rankl and osteoprotegerin observed in the same tissue samples. RA treatment of juvenile explants had no effect on runt-related transcription factor 2 and osterix mRNA levels. However, osterix was significantly down-regulated in 25 dph cod head explants following RA treatment. In situ hybridizations revealed differential spatial distribution of the two isoforms and the predominant expression of cathepsin K in bone surrounding tissues. The present study indicates that RA causes a shift in the balance between osteoclast activity and osteoblast activity in favor of the latter. PMID- 22075543 TI - Clinical factors associated with malignancy and HIV status in patients with ocular surface squamous neoplasia at Kilimanjaro Christian Medical Centre, Tanzania. AB - AIMS: To describe the clinical characteristics of ocular surface squamous neoplasia (OSSN) in a sub-Saharan referral hospital setting according to histopathological diagnosis and HIV status. METHODS: All patients were enrolled who presented consecutively to the Kilimanjaro Christian Medical College eye department with lesions suspected to be OSSN from September 2005 to May 2007 and from February 2008 to September 2008. Clinical characteristics were documented on a standardised form, excision biopsies were performed and histopathological diagnosis was obtained on all cases. Data were analysed to look for associations among various factors. RESULTS: 150 patients were enrolled. Histopathological study showed OSSN in 88% of cases. Of these, 128 (85.6%) were under the age of 50 years and 60% were HIV positive. The median CD4 cell count was 71 cells/MUl among HIV-positive cases. Independent of size, the lesions of patients who were HIV positive were more likely to be higher grade malignancy than those who were HIV negative. CONCLUSION: In a sub-Saharan setting, OSSN occurs in persons who are younger than in industrialised countries and is often associated with HIV positivity. CD4 cell counts indicate that a majority of HIV-positive patients with OSSN are significantly immunosuppressed at presentation. Higher grade malignancy in this group could indicate a more aggressive course. PMID- 22075545 TI - Atrial fibrillation (chronic). AB - INTRODUCTION: Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? What is the effect of different treatment strategies (rate versus rhythm) for people with persistent non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (with or without digoxin), calcium channel blockers (with or without digoxin), calcium channel blockers (rate limiting), digoxin, and rate versus rhythm control strategies. PMID- 22075544 TI - Kidney stones. AB - INTRODUCTION: The age of peak incidence for stone disease is 20 to 40 years, although stones are seen in all age groups. There is a male to female ratio of 3:2. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions for stone removal in people with asymptomatic kidney stones? What are the effects of interventions for the removal of symptomatic renal stones? What are the effects of interventions to remove symptomatic ureteric stones? What are the effects of interventions for the management of acute renal colic? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antispasmodic drugs, extracorporeal shockwave lithotripsy, intravenous fluids, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, oral fluids, percutaneous nephrolithotomy, and ureteroscopy. PMID- 22075546 TI - Silylation products of cyclic tri-aminal carbanions and their lithiation. AB - The structure of 1,3,5-trimethyl-1,3,5-triaza-cyclohexane (TMTAC) was determined by single crystal X-ray diffraction and compared with earlier gas-phase data. It shows a preference for an aee-conformation in all phases. Lithiated TMTAC, [(RLi)(2).(RH)] (1) (R = 2,4,6-trimethyl-2,4,6-triaza-cyclohex-1-yl), was reacted with Et(3)SiCl, Ph(3)SiCl and PhMe(2)SiCl to afford the substituted silanes Et(3)SiR (1), Ph(3)SiR (2) and PhMe(2)SiR (3) in moderate yields. They were characterised by NMR spectroscopy ((1)H, (13)C, (29)Si). 1 reacts with Me(2)SiCl(2) and Ph(2)SiCl(2) to give Me(2)SiR(2) (5) and Ph(2)SiR(2) (6) which were characterised by NMR spectroscopy. 5 was also identified by crystal structure determination. Analogous triple substitution could not be observed by employing trichlorosilanes. Quantumchemical calculations explain this by sterical overcrowding of the silicon atom. The reaction of 1 with SiCl(4) did not yield fourfold substitution but a formal insertion product of SiCl(2) into a C-N bond of the TMTAC ring (2,4,6-trimethyl-2,4,6-triaza-1,1-dichloro-1-sila-cycloheptane, 7) in very small quantities. It was identified by X-ray crystallography and shows an intramolecular Si...N dative bond. The reactions of (3) and (5) with n-butyl lithium afforded lithiation of the silicon bound methyl groups in both cases. The products, 8 and 9, were characterised by NMR spectroscopy ((1)H, (13)C, (29)Si), 8 was also characterised by X-ray crystallography. PMID- 22075547 TI - A proteomic analysis of differential cellular responses to the short-chain fatty acids butyrate, valerate and propionate in colon epithelial cancer cells. AB - The short chain fatty acids (SCFAs) are inhibitors of histone deacetylases (HDACi); they are produced naturally in the colon by fermentation. They affect cellular processes at a molecular and transcriptional level, the mechanisms of which may involve large numbers of proteins and integrated pathways. Butyrate is the most biologically potent of the SCFAs in colon epithelial cells, inhibiting human colon carcinoma cell proliferation and inducing apoptosis in vitro. In order to investigate the hypothesis that propionate and valerate possess unique and independent actions from butyrate, we combined proteomic and cellomic approaches for large-scale comparative analysis. Proteomic evaluation was undertaken using an iTRAQ tandem mass-spectrometry workflow and high-throughput High-content Analysis microscopy (HCA) was applied to generate cellomic information on the cell cycle and the cytoskeletal structure. Our results show that these SCFAs possess specific effects. Butyrate was shown to have more pronounced effects on the keratins and intermediate filaments (IFs); while valerate altered the beta-tubulin isotypes' expression and the microtubules (MTs); propionate was involved in both mechanisms, displaying intermediate effects. These data suggest distinct physiological roles for SCFAs in colon epithelial function, offering new possibilities for cancer therapeutics. PMID- 22075548 TI - The probability distribution of ranked gene trees on a species tree. AB - The properties of random gene tree topologies have recently been studied under a coalescent model that treats a species tree as a fixed parameter. Here we develop the analogous theory for random ranked gene tree topologies, in which both the topology and the sequence of coalescences for a random gene tree are considered. We derive the probability distribution of ranked gene tree topologies conditional on a fixed species tree. We then show that similar to the unranked case, ranked gene trees that do not match either the ranking or the topology of the species tree can have greater probability than the matching ranked gene tree. PMID- 22075549 TI - Population pharmacokinetics and pharmacogenetics of tacrolimus in healthy Chinese volunteers. AB - AIM: The aim of this study was to establish population pharmacokinetic models of tacrolimus in healthy Chinese volunteers. METHODS: A total of 956 tacrolimus whole blood concentrations from 73 healthy volunteers were determined using ultraperformance liquid chromatography mass spectrometry/mass spectrometry. Population pharmacokinetic analyses were performed using NONMEM. The final population pharmacokinetic models were validated with bootstrap and visual predictive check. A number of covariates were analyzed, including CYP3A5 and ABCB1 polymorphism, demographic characteristics and hematological and biological indices. RESULTS: The structural model was a two-compartment model with first order absorption, and a lag time was fitted to the data. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V(2)/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V(3)/F), absorption rate (ka) and lag time (ALAG) were 27.7 l/h, 37.5 liters, 34.4 l/h, 357 liters, 0.795 h(-1) and 0.226 h, respectively. The interindividual variabilities of these parameters were 63.3, 62.0, 50.8, 52.3, 32.9 and 4.45%, respectively, and the intraindividual variability of observed concentrations was 14.9%. The covariates that were retained in the final models were CYP3A5 genotype on CL/F, and body surface area and red blood count on V(3)/F. CONCLUSION: Population pharmacokinetic models of tacrolimus were developed in healthy volunteers. These results could provide a reference for individualized tacrolimus therapy in the clinical setting. PMID- 22075550 TI - The health sector reforms and the efficiency of public hospitals in Turkey: provincial markets. AB - BACKGROUND: Turkey initiated the 'Health Transformation Programme' (HTP) in 2003 to align its health care system with the European Union and OECD countries. This study investigates the impact of these reforms on the efficiency of public hospitals. Our study would contribute to the existing literature with a comprehensive analysis of the health system in a developing country. METHODS: We employ the data envelopment approach and the Malmquist index to comparatively examine before and after the reform years. Our analyses compare the performances of public hospitals served in provincial markets. Inputs of number of beds, number of primary care physician, and number of specialists, and how they are used to produce outputs of inpatient discharges, outpatient visits and surgical operations are investigated. Indeed, as the performance indicators dead rate, hospital bed occupation rate and average length of stay are considered. RESULTS: The HTP was generally successful in boosting productivity due to advancements in technology and technical efficiency but in the socio-economically disadvantaged provinces productivity gains have not been achieved. The average technical efficiency gains took place because of the significantly improved scale efficiencies, as the average pure technical efficiency slightly improved. Lastly, the hospital performance indicators have not improved in the short run. CONCLUSION: It appears that the expected benefits from the health reforms in Turkey have been partially achieved in the short run. PMID- 22075551 TI - Zoledronic acid modulates maturation of human monocyte-derived dendritic cells. AB - Zoledronic acid (ZA) is a drug of the bisphosphonate class, which is widely used for the treatment of both osteoporosis and skeletal metastasis. Besides its main bone antiresorptive activity, ZA displays antitumor properties, by triggering the expansion and activation of gammadelta T-cells, which exert an antitumor effect through dendritic cells (DCs). Several studies have reported the interaction between ZA and gammadelta T-cells, but the potential immunoregulatory activity of this drug on DCs has scarcely been investigated. Therefore, in this paper, we evaluated the effects of a therapeutic dose of ZA on the in vitro generation and maturation of DCs derived from peripheral blood monocytes of healthy adult donors. We demonstrate that ZA treatment did not affect DC differentiation, but inhibited DC maturation on lipopolysaccharide activation, as shown by the impaired expression of maturation surface markers and reduced ability to induce allogeneic T-cell proliferation. Interestingly, IL-10 secretion by mature DCs was significantly lower in ZA-treated cells than in controls. We conclude that ZA exerts its immunological in vitro activity also by modulating the maturation of DCs. PMID- 22075552 TI - Diet-induced obesity suppresses sevoflurane preconditioning against myocardial ischemia-reperfusion injury: role of AMP-activated protein kinase pathway. AB - Obesity is a major risk factor for coronary artery disease, but its impact on anesthetic-induced cardioprotective actions is unexplored. We tested whether obesity inhibits anesthetic sevoflurane-induced preconditioning and whether this effect is mediated via the AMP-activated protein kinase (AMPK) signaling pathway. Sprague-Dawley rats were fed a high-fat (HF, 45% kcal as fat) or low-fat (LF, 10% kcal as fat) diet for 12 weeks. HF-fed rats developed metabolic disturbances including visceral obesity, hyperinsulinemia, hyperleptinemia and dyslipidemia. HF- or LF-fed rats subjected to 25 min of myocardial ischemia followed by 120 min of reperfusion were assigned to the following groups: control, sevoflurane preconditioning, sevoflurane plus AMPK inhibitor ara-A or AMPK activator A769662 alone. Infarct size was similar between the two control groups. Sevoflurane preconditioning significantly reduced infarct size in LF-fed rats but failed to induce cardioprotection in HF-fed rats. Phosphorylation of AMPK and endothelial nitric oxide synthase, as well as myocardial nitrite and nitrate, were also increased by sevoflurane preconditioning in LF-fed rats but not in HF-fed rats. Pretreatment with ara-A inhibited phosphorylation of AMPK and reversed sevoflurane preconditioning-induced cardioprotection in LF-fed rats, whereas it had no effects in HF-fed rats. In addition, sevoflurane preconditioning failed to enhance reactive oxygen species (ROS) generation in the myocardium of HF-fed rats compared with LF-fed rats. Direct activation of AMPK with A769662 equally increased phosphorylation of AMPK and reduced infarct size in both LF- and HF-fed rats. The results suggest that diet-induced obesity suppresses sevoflurane preconditioning-induced cardioprotective action, probably due to a diminished effect of sevoflurane preconditioning on activation of the ROS-mediated AMPK signaling pathway. PMID- 22075553 TI - Implantation of biomaterial as an efficient method to harvest mesenchymal stem cells. AB - Autologous mesenchymal stem cell (MSC) transplants have been used successfully to treat a number of diseases, and patients undergoing cell transplantation must have stem cells collected before transplantation. In this study, we developed a new method to harvest MSCs. Biomaterials were implanted into the spatium intermuscular of mice hind limbs, and a large number of migrating cells (MCs) were isolated from the transplanted biomaterials. The adherent cells in MCs showed the characteristics of MSCs. Further comparative study demonstrated that the characteristics of MC-MSCs were similar to that of bone marrow (BM)-MSCs, including morphology, phenotype, proliferation potential, multilineage differentiation capacity and hematopoiesis-supportive function. The colony forming unit-fibroblast frequency of the MCs was equivalent to approximately 20 fold of that of the BM. In addition, a BM transplantation experiment demonstrated that MC-MSCs were derived from the peripheral blood. In conclusion, we successfully establish an efficient method to harvest MSCs, and together with the distinct advantages of this method, such as accessibility and possibility for autologous cell therapy, we conclude that our efficient method may be a promising alternative for clinical application. PMID- 22075554 TI - Hsp40 regulates the amount of keratin proteins via ubiquitin-proteasome pathway in cultured human cells. AB - Keratins represent important structural components of intermediate filament proteins. Their expression profiles are remarkably tissue-specific. Recent data have shown that keratins associate with many proteins including heat shock proteins (HSP). We recently identified cell-specific keratin and HSP expression. We aimed to gain further insight into the regulation of keratins by specific inhibition through knockdown of Hsp40 in human keratinocyte cells. Keratin-HSP interaction in HaCaT cell lysate was evaluated by immunoprecipitation followed by Western blotting. Immunofluorescence, was used to examine the co-localization of keratins and Hsp40. Hsp40 depletion led to an increase in the levels of keratin proteins (K5, K14, K10) and a decrease in keratin ubiquitination without influencing keratin gene expression. Our results demonstrate direct or indirectly association of Hsp40 and imply that expressed keratin proteins were regulated by Hsp40 depending on the ubiquitin-proteasome pathway in HaCaT. Furthermore, the K10 differentiation marker was increased by knockdown of Hsp40. The results presented in this study indicate that Hsp40 is related to the differentiation exchange of keratin pairs. PMID- 22075555 TI - Genetically modified T cells targeting interleukin-11 receptor alpha-chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases. AB - The treatment of osteosarcoma pulmonary metastases remains a challenge. T cells genetically modified to express a chimeric antigen receptor (CAR), which recognizes a tumor-associated antigen, have shown activity against hematopoietic malignancies in clinical trials, but this requires the identification of a specific receptor on the tumor cell. In the current study, we found that interleukin (IL)-11Ralpha was selectively expressed on 14 of 16 osteosarcoma patients' lung metastases and four different human osteosarcoma cell lines, indicating that IL-11Ralpha may be a novel target for CAR-specific T-cell therapy. IL-11Ralpha expression was absent or low in normal organ tissues, with the exception of the gastrointestinal tract. IL-11Ralpha-CAR-specific T cells were obtained by non-viral gene transfer of Sleeping Beauty DNA plasmids and selectively expanded ex vivo using artificial antigen-presenting cells derived from IL-11Ralpha + K562 cells genetically modified to coexpress T-cell costimulatory molecules. IL-11Ralpha-CAR(+) T cells killed all four osteosarcoma cell lines in vitro; cytotoxicity correlated with the level of IL-11Ralpha expression on the tumor cells. Intravenous injection of IL-11Ralpha-CAR(+) T cells into mice resulted in the regression of osteosarcoma pulmonary metastases with no organ toxicity. Together, the data suggest that IL-11Ralpha-CAR T cells may represent a new therapy for patients with osteosarcoma pulmonary metastases. PMID- 22075556 TI - AKT inhibition by triciribine alone or as combination therapy for growth control of gastroenteropancreatic neuroendocrine tumors. AB - Up-regulation of phosphatidylinositol-3-kinase (PI3K)-AKT signaling facilitates tumor cell growth and inhibits cell demise. The AKT-pathway also plays an important role in cytostatic therapy resistance and response to hypoxia and angiogenesis. Using real-time cell proliferation assay we examined the potency of triciribine in three distinct neuroendocrine gastrointestinal tumor cell lines. Also we investigated triciribine's induction of apoptosis and effects on a broad range of cancer-associated gene products. Furthermore, we characterized the role of PTEN as a possible predictor of sensitivity to triciribine in GEP-NETs. We also looked for additive anti-neoplastic effects of triciribine when combined with conventional cytostatic drugs or other targeted drugs, affecting different molecules of the PI3K-AKT-pathway and we assessed the potency of triciribine to inhibit tumor growth in vivo, by using the chick chorioallantoic membrane assay. Treatment of insulinoma (CM) or gut neuroendocrine tumor cells (STC-1) with triciribine significantly reduced tumor cell growth by 59% and 65%, respectively. By contrast, the highly expressing PTEN carcinoid cell line BON did not respond, even at higher doses. Combinations of triciribine with classic cytostatic drugs as well as drugs targeting other molecules of the PI3K-AKT-pathway led to synergistic anti-proliferative effects. Additional in vivo-evaluations confirmed the anti-neoplastic potency of triciribine. Thus, our data show that inhibition the AKT-pathway potently reduces the growth of GEP-NET cells alone or in combination therapies. AKT inhibition may provide a rationale for future evaluations. PMID- 22075557 TI - Role of hypoxia-inducible-1alpha in hepatocellular carcinoma cells using a Tet-on inducible system to regulate its expression in vitro. AB - Hypoxia-inducible-1alpha (HIF-1alpha) expression was intimately correlated with apoptosis and proliferation of cancer cells. However, conclusions of different studies on the effects of HIF-1alpha expression on cell apoptosis and cell proliferation of hepatoma cells remain controversial. In view of the current status, we reassess its roles and possible mechanism in hepatoma cells. In order to acquire more convincing and reliable results, we used a Tet-on system to stably and effectively regulate HIF-1alpha expression in the HepG2 cells in vitro. In our study we not only confirmed some common conclusions of previous studies, but also acquired some different and significant results that HIF-1alpha facilitates cell proliferation and cell cycle through influencing the expression of cyclin A and cyclin D, and suppresses cell apoptosis through inducing the expression of survivin and Bcl-2. These results further enrich our knowledge on the role of HIF-1alpha expression on cell apoptosis and cell proliferation of hepatoma cells. PMID- 22075558 TI - Seasonal changes in immunoreactivity of activin signaling component proteins in wild ground squirrel testes. AB - The seasonal spermatogenesis and localization of inhibin/activin subunits (alpha, betaA, betaB) in the testes of wild ground squirrel has been previously described; however, the expression pattern of activin receptors and cytoplasmic signaling SMADs has not been detected in any seasonal breeders. The objective of this study was to investigate the abundance and cellular localization of activin signaling components in testes of the wild ground squirrel during the breeding and nonbreeding seasons. The immunolocalizations of ActRIIB (activin type II receptor B) and activin-related SMADs (phospho-SMAD2/3, SMAD4 and SMAD7) were observed by immunohistochemistry. Total proteins were extracted from testicular tissues in the breeding and nonbreeding seasons and were used for Western blotting analysis for ActRIIB and SMADs. Immunoreactivities of activin signaling components were greater in the testes of the breeding season, and then decreased to a relatively low level in the nonbreeding season. ActRIIB and related SMADs were widely spread in the active testes, while spermatogonia were the predominant cellular sites of activin signal transduction during arrested spermatogenesis. The dynamic regulation of activin type II receptor and SMADs indicated that the activin signal pathway played an important paracrine role in seasonal spermatogenesis of the wild ground squirrel. Furthermore, the distinct localizations and immunoreactivity of ActRIIB and SMADs might suggest different functions of activin in seasonal spermatogenesis. PMID- 22075559 TI - Normal calves produced after transfer of embryos cultured in a chemically defined medium supplemented with epidermal growth factor and insulin-like growth factor I following ovum pick up and in vitro fertilization in Japanese black cows. AB - The objective of this study was to examine whether high concentrations of epidermal growth factor (EGF) and/or insulin-like growth factor I (IGF-I) would have a beneficial effect on bovine embryo development in vitro and to obtain normal calves by using an ovum pick up method and embryo culture in a chemically defined medium. When compared with controls, EGF (100 or 200 ng/ml) or IGF-I (50 or 100 ng/ml) significantly increased the rate of embryos that developed into blastocysts during an 8-day culture after the in vitro fertilization of oocytes obtained from ovaries from a slaughterhouse. IGF-I induced a dose-dependent increase in cell number in both the inner cell mass and the trophectoderm, whereas EGF stimulated proliferation only in the inner cell mass. A combination of EGF (100 ng/ml) and IGF-I (50 ng/ml) produced an additive effect, and embryos developed into blastocysts at a comparatively high rate (27.9%) compared with controls (12.0%). A similar rate of development was achieved using a combination of EGF and IGF-I in the culture of embryos following ovum pick up by ultrasound guided transvaginal follicular aspiration and in vitro fertilization, and 5 blastocysts that developed after the culture were transferred into uteri; two embryos implanted, and normal calves were born. These results suggest that the combined use of EGF and IGF-I makes bovine embryo culture in a chemically defined medium a practical and useful procedure for producing blastocysts, and its application to embryo culture following ovum pick up and in vitro fertilization could be useful for producing normal calves. PMID- 22075560 TI - The secretory pattern and source of immunoreactive prolactin in pregnant African (Loxodonta africana) and Asian (Elephas maximus) elephants. AB - The objective of the present study was to define the secretion of prolactin (PRL) in pregnant African and Asian elephants. Levels of immunoreactive (ir-) PRL in serum and placental homogenates were measured by a heterologous radioimmunoassay (RIA) based on an ovine and human RIA system, and the localization of ir-PRL in the placenta was detected by immunohistochemistry using anti-human PRL. Circulating ir-PRL clearly showed a biphasic pattern during pregnancy in African and Asian elephants. Serum levels of ir-PRL started to increase from the 4 - 6th month of gestation and reached the first peak level around the 11-14th month. A second peak of circulating ir-PRL levels was observed around the 18-20th month of gestation followed by an abrupt decline after parturition. In contrast, in a case of abortion of an African elephant, the second peak of ir-PRL was not observed, and the levels remained low for about four months until parturition. The weight of the fetus delivered at the 17th month of gestation was 23.5 kg, which was quite small compared with normal fetuses in previous reports. Ir-PRL was detected in placental homogenates, and immunolocalization was observed in trophoblasts in both the African and Asian elephants, indicating that the placenta is the source of ir-PRL during pregnancy in elephants. The present results clearly demonstrated that circulating ir-PRL shows a biphasic pattern during normal pregnancy and that the placenta appears to be an important source of circulating ir-PRL during pregnancy in both African and Asian elephants. PMID- 22075561 TI - Double Sigmoid colon perforation due to migration of a biliary stent. AB - Migration of pancreatico-biliary stents is a rare event, usually benign, but which can lead to severe complications such as digestive tube perforation. We report the case of a patient with double sigmoid perforation due to distal migration of a biliary stent placed to decompress a pancreatic head carcinoma. PMID- 22075562 TI - Damage control laparotomy. PMID- 22075563 TI - Probing the oligomeric state and interaction surfaces of Fukutin-I in dilauroylphosphatidylcholine bilayers. AB - Fukutin-I is localised to the endoplasmic reticulum or Golgi apparatus within the cell, where it is believed to function as a glycosyltransferase. Its localisation within the cell is thought to to be mediated by the interaction of its N-terminal transmembrane domain with the lipid bilayers surrounding these compartments, each of which possesses a distinctive lipid composition. However, it remains unclear at the molecular level how the interaction between the transmembrane domains of this protein and the surrounding lipid bilayer drives its retention within these compartments. In this work, we employed chemical cross-linking and fluorescence resonance energy transfer measurements in conjunction with multiscale molecular dynamics simulations to determine the oligomeric state of the protein within dilauroylphosphatidylcholine bilayers to identify interactions between the transmembrane domains and to ascertain any role these interactions may play in protein localisation. Our studies reveal that the N-terminal transmembrane domain of Fukutin-I exists as dimer within dilauroylphosphatidylcholine bilayers and that this interaction is driven by interactions between a characteristic TXXSS motif. Furthermore residues close to the N-terminus that have previously been shown to play a key role in the clustering of lipids are shown to also play a major role in anchoring the protein in the membrane. PMID- 22075564 TI - Double and triple in situ hybridization for coexpression studies: combined fluorescent and chromogenic detection of neuropeptide Y (NPY) and serotonin receptor subtype mRNAs expressed at different abundance levels. AB - Multiple fluorescence in situ hybridization is the method of choice for studies aimed at determining simultaneous production of signal transduction molecules and neuromodulators in neurons. In our analyses of the monoamine receptor mRNA expression of peptidergic neurons in the rat telencephalon, double tyramide signal-amplified fluorescence in situ hybridization delivered satisfactory results for coexpression analysis of neuropeptide Y (NPY) and serotonin receptor 2C (5-HT2C) mRNA, a receptor subtype expressed at high-to-moderate abundance in the regions analyzed. However, expression of 5-HT1A mRNA, which is expressed at comparatively low abundance in many telencephalic areas, could not be unequivocally identified in NPY mRNA-reactive neurons due to high background and poor signal-to-noise ratio in fluorescent receptor mRNA detections. Parallel chromogenic in situ hybridization provided clear labeling for 5-HT1A mRNA and additionally offered the possibility to monitor the chromogen deposition at regular time intervals to determine the optimal signal-to-noise ratio. We first developed a double labeling protocol combining fluorescence and chromogenic in situ hybridization and subsequently expanded this variation to combine double fluorescence and chromogenic in situ hybridization for triple labelings. With this method, we documented expression of 5-HT2C and/or 5-HT1A in subpopulations of telencephalic NPY-producing neurons. The method developed in the present study appears suitable for conventional light and fluorescence microscopy, combines advantages of fluorescence and chromogenic in situ hybridization protocols and thus provides a reliable non-radioactive alternative to previously published multiple labeling methods for coexpression analyses in which one mRNA species requires highly sensitive detection. PMID- 22075565 TI - Differential vascular expression and regulation of oncofetal tenascin-C and fibronectin variants in renal cell carcinoma (RCC): implications for an individualized angiogenesis-related targeted drug delivery. AB - The study was aimed at determining the vascular expression of oncofetal fibronectin (oncfFn) and tenascin-C (oncfTn-C) isoforms in renal cell carcinoma (RCC) and its metastases which are well-known targets for antibody-based pharmacodelivery. Furthermore, the influence of tumour cells on endothelial mRNA expression of these molecules was investigated. Evaluation of vascular ED-A(+) and ED-B(+) Fn as well as A1(+) and C(+) Tn-C was performed after immunofluorescence double and triple staining using human recombinant antibodies on clear cell, papillary and chromophobe primary RCC and metastases. The influence of hypoxic RCC-conditioned medium on oncfFn and oncfTn-C mRNA expression was examined in human umbilical vein endothelial cells (HUVEC) by real time RT-PCR. There are RCC subtype specific expression profiles of vascular oncfFn and oncfTn-C and corresponding patterns when comparing primary tumours and metastases. Within one tumour, there are different vessel populations with regard to the incorporation of oncfTn-C and oncfFn into the vessel wall. In vitro tumour derived soluble mediators induce an up regulation of oncfTn-C and oncfFn mRNA in HUVEC which can be blocked by Avastin((r)). Vascular expression of oncFn and oncTn-C variants depends on RCC subtype and may reflect an individual tumour stroma interaction or different stages of vessel development. Therefore, oncFn or oncTn-C variants can be suggested as molecular targets for individualized antibody based therapy strategies in RCC. Tumour-derived VEGF could be shown to regulate target expression. PMID- 22075566 TI - Identification of SAMT family proteins as substrates of MARCH11 in mouse spermatids. AB - MARCH11, a RING-finger transmembrane ubiquitin ligase, is predominantly expressed in spermatids and localized to the trans-Golgi network (TGN) and multivesicular bodies (MVBs). Because ubiquitination acts as a sorting signal of cargo proteins, MARCH11 has been postulated to mediate selective protein sorting via the TGN-MVB pathway. However, the physiological substrate of MARCH11 has not been identified. In this study, we have identified and characterized SAMT1, a member of a novel 4 transmembrane protein family, which consists of four members. Samt1 mRNA and its expression product were found to be specific to the testis and were first detected in germ cells 25 days after birth in mice. Immunohistochemical analysis further revealed that SAMT1 was specifically expressed in haploid spermatids during the cap and acrosome phases. Confocal microscopic analysis showed that SAMT1 co-localized with MARCH11 as well as with fucose-containing glycoproteins, another TGN/MVB marker, and LAPM2, a late endosome/lysosome marker. Furthermore, we found that MARCH11 could increase the ubiquitination of SAMT1 and enhance its lysosomal delivery and degradation in an E3 ligase activity-dependent manner. In addition, the C-terminal region of SAMT1 was indispensable for its ubiquitination and proper localization. The other member proteins of the SAMT family also showed similar expression profile, intracellular localization, and biochemical properties, including ubiquitination by MARCH11. These results suggest that SAMT family proteins are physiological substrates of MARCH11 and are delivered to lysosomes through the TGN-MVB pathway by a ubiquitin-dependent sorting system in mouse spermatids. PMID- 22075567 TI - Eosinophilic esophagitis: from a sneaking suspicion to a clear diagnosis. PMID- 22075568 TI - Metal to ligand charge transfer induced DNA photobinding in a Ru(II)-Pt(II) supramolecule using red light in the therapeutic window: a new mechanism for DNA modification. AB - The Ru(II)-Pt(II) supramolecular complex, [(Ph(2)phen)(2)Ru(dpp)PtCl(2)](2+), displays a new mechanism for DNA modification: photobinding through a (3)MLCT excited state. Gel shift analysis, selective DNA precipitation, and DNA melting point experiments support efficient covalent DNA binding following visible light excitation. PMID- 22075569 TI - Association of RIP2 gene polymorphisms and systemic lupus erythematosus in a Chinese population. AB - The aim of this study was to investigate the association of receptor interacting protein 2 (RIP2) single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A case-control study was performed on the SNPs rs16900617 and rs16900627 in 590 Chinese SLE patients and 660 healthy controls. These SNPs were typed by TaqMan allele discrimination assays. We found a significant association of rs16900617 G allele [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.41-0.72] and rs16900627 G allele (OR = 1.28, 95% CI 1.04-1.58) with SLE. Significant differences in genotype frequency distribution were also found in SLE and control individuals (rs16900617: AG versus AA, OR = 0.59, 95% CI 0.44-0.81; GG versus AA, OR = 0.08, 95% CI 0.01 0.65; AG + GG versus AA, OR = 0.55, 95% CI 0.41-0.75; rs16900627: AG versus AA, OR = 1.51, 95% CI 1.17-1.93; AG + GG versus AA, OR = 1.43, 95% CI 1.13-1.82). Analysis of the haplotypes revealed that two haplotypes of AG and GA were also significantly associated with SLE (OR = 1.37, 95% CI 1.11-1.70; OR = 0.60, 95% CI 0.45-0.79). Our findings suggest that the RIP2 gene polymorphisms may be associated with susceptibility to SLE in the Chinese population. PMID- 22075570 TI - Arbuscular mycorrhizal fungi in national parks, nature reserves and protected areas worldwide: a strategic perspective for their in situ conservation. AB - Soil fungi play a crucial role in producing fundamental ecosystem services such as soil fertility, formation and maintenance, nutrient cycling and plant community dynamics. However, they have received little attention in the field of conservation biology. Arbuscular mycorrhizal fungi (AMF) are beneficial soil symbionts fulfilling a key function in the complex networks of belowground/aboveground biotic interactions as they live in association with the roots of most (80%) land plant families and influence not only soil fertility but also plant nutrition, diversity and productivity. The diversity of AMF communities can decline due to habitat loss and anthropogenic disturbance, especially in agro-ecosystems, and many valuable ecotypes could become extinct before they are even discovered. Consequently, long-term strategies are urgently needed to ensure their conservation in habitats where they naturally occur and have evolved. Protected areas, where living organisms are under the care of national and international authorities, represent an appropriate place for the in situ conservation of AMF, providing them with adapted situations together with established complex networks of interactions with different components within each specific ecosystem. Here, we review data available about the main present day threats to AMF and the current state of knowledge about their occurrence in protected sites worldwide, providing a checklist of national parks and nature reserves where they have been reported. The aim was to offer a strategic perspective to increase awareness of the importance of conserving these beneficial plant symbionts and of preserving their biodiversity in the years to come. PMID- 22075571 TI - Succinobucol's new coat--conjugation with steroids to alter its drug effect and bioavailability. AB - Synthesis, detailed structural characterization (X-ray, NMR, MS, IR, elemental analysis), and studies of toxicity, antioxidant activity and bioavailability of unique potent anti-atherosclerotic succinobucol-steroid conjugates are reported. The conjugates consist of, on one side, the therapeutically important drug succinobucol ([4-{2,6-di-tert-butyl-4-[(1-{[3-tert-butyl-4-hydroxy-5-(propan-2 yl)phenyl]sulfanyl}ethyl)sulfanyl]phenoxy}-4-oxo-butanoic acid]) possessing an antioxidant and anti-inflammatory activity, and on the other side, plant stanol/sterols (stigmastanol, beta-sitosterol and stigmasterol) possessing an ability to lower the blood cholesterol level. A cholesterol-succinobucol prodrug was also prepared in order to enhance the absorption of succinobucol through the intestinal membrane into the organism and to target the drug into the place of lipid metabolism-The enterohepatic circulation system. Their low toxicity towards mice fibroblasts at maximal concentrations, their antioxidant activity, comparable or even higher than that of ascorbic acid as determined by direct quenching of the DPPH radical, and their potential for significantly altering total and LDL cholesterol levels, suggest that these conjugates merit further studies in the treatment of cardiovascular or other related diseases. A brief discussion of succinobucol's ability to quench the radicals, supported with a computational model of the electrostatic potential mapped on the electron density surface of the drug, is also presented. PMID- 22075572 TI - Indatraline: synthesis and effect on the motor activity of Wistar rats. AB - A new approach for the synthesis of indatraline was developed using as the key step an iodine(III)-mediated ring contraction of a 1,2-dihydronaphthalene derivative. Behavioral tests were conducted to evaluate the effect of indatraline and of its precursor indanamide on the motor activity of Wistar rats. Specific indexes for ambulation, raising and stereotypy were computed one, two and three hours after i.p. drug administration. Indatraline effects on motor activity lasted for at least three hours. On the other hand, no significant differences in motor activity were observed using indanamide. The results suggest that indatraline has a long lasting effect on motor activity and add evidence in favor of the potential use of that compound as a substitute in cocaine addiction. PMID- 22075573 TI - Antioxidant activity and total phenols from the methanolic extract of Miconia albicans (Sw.) Triana leaves. AB - Miconia is one of the largest genus of the Melastomataceae, with approximately 1,000 species. Studies aiming to describe the diverse biological activities of the Miconia species have shown promising results, such as analgesic, antimicrobial and trypanocidal properties. M. albicans leaves were dried, powdered and extracted to afford chloroformic and methanolic extracts. Total phenolic contents in the methanolic extract were determined according to modified Folin-Ciocalteu method. The antioxidant activity was measured using AAPH and DPPH radical assays. Chemical analysis was performed with the n-butanol fraction of the methanolic extract and the chloroformic extract, using different chromatographic techniques (CC, HPLC). The structural elucidation of compounds was performed using 500 MHz NMR and HPLC methods. The methanolic extract showed a high level of total phenolic contents; the results with antioxidant assays showed that the methanolic extract, the n-butanolic fraction and the isolated flavonoids from M. albicans had a significant scavenging capacity against AAPH and DPPH. Quercetin, quercetin-3-O-glucoside, rutin, 3-(E)-p-coumaroyl-alpha-amyrin was isolated from the n-butanolic fraction and alpha-amyrin, epi-betulinic acid, ursolic acid, epi-ursolic acid from the chloroformic extract. The results presented in this study demonstrate that M. albicans is a promising species in the search for biologically active compounds. PMID- 22075575 TI - Brief report: the temporal stability of the Repeatable Battery for the Assessment of Neuropsychological Status Effort Index in geriatric samples. AB - The Effort Index (EI) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was developed to identify inadequate effort. Although researchers have examined its validity, the reliability of the EI has not been evaluated. The current study examined the temporal stability of the EI across 1 year in two independent samples of older adults. One sample consisted of 445 cognitively intact older adults (mean age = 72.89; 59% having 12-15 years of education) and the second sample consisted of 51 individuals diagnosed with amnestic Mild Cognitive Impairment (mean age = 82.41; 41% having 12-15 years of education). For both samples, the EI was found to have low stability (Spearman's rho = .32-.36). When participants were divided into those whose EI stayed stable or improved versus those whose EI worsened (i.e., declining effort) on retesting, it was observed that individuals with lower baseline RBANS Total scores tended to worsen on the EI across time. Overall, the findings suggest low temporal stability of the EI in two geriatric samples. In particular, individuals with poorer cognition at baseline could present with poorer effort across time. These findings also suggest the need to further examine the temporal stability of other effort measures. PMID- 22075574 TI - Anti-inflammatory and free radial scavenging activities of the constituents isolated from Machilus zuihoensis. AB - A new biflavonol glycoside, quercetin-3-O-beta-D-glucopyranoside-(3'->O-3''') quercetin-3-O-beta-D-galactopyranoside (9), together with eight known compounds was isolated for the first time from the leaves of Machilus zuihoensis Hayata (Lauraceae). The structure of compound 9 was elucidated by various types of spectroscopic data analysis. Analysis of the biological activity assay found that compound 9 showed significant superoxide anion scavenging activity (IC50 is 30.4 MUM) and markedly suppressed LPS-induced high mobility group box 1 (HMGB-1) protein secretion in RAW264.7 cells. In addition, the HMGB-1 protein secretion was also inhibited by quercitrin (3), ethyl caffeate (6), and ethyl 3-O caffeoylquinate (7) treatment. In the LPS-stimulated inducible nitric oxide synthase (iNOS) activation analysis, two known compounds, quercetin (1) and ethyl caffeate (6), were found to markedly suppress nitric oxide (NO) production (IC50 value, 27.6 and 42.9 MUM, respectively) in RAW264.7 cells. Additionally, it was determined that ethyl caffeate (6) down-regulated mRNA expressions of iNOS, IL 1beta, and IL-10 in the LPS-treatment of RAW264.7 cells via a suppressed NF-kB pathway. These results suggested for the first time that the new compound 9 and other constituents isolated from M. zuihoensis have potential anti-inflammatory and superoxide anion scavenging effects. These constituents may be useful for treating various inflammatory diseases. PMID- 22075576 TI - Evaluation of embedded malingering indices in a non-litigating clinical sample using control, clinical, and derived groups. AB - Although recent findings have indicated that a portion of college students presenting for psychoeducational evaluations fail validity measures, methods for determining the validity of cognitive test results in psychoeducational evaluations remain under-studied. In light of this, data are needed to evaluate utility of validity indices in this population and to provide base rates for students meeting research criteria for malingering and to report the relationship between testing performance and the level of external incentive. The authors utilized archival data from: (i) a university psychological clinic (n = 986) and (ii) a university control sample (n = 182). Empirically supported embedded validity indices were utilized to identify retrospectively suspected malingering patients. Group performance, according to invalidity and the level of incentive seeking, was evaluated through a series of multivariate mean comparisons. The current study supports classifying patients according to the level of incentive seeking when evaluating neurocognitive performance and feigned/exaggerated deficits. PMID- 22075577 TI - Using pathway modules as targets for assay development in xenobiotic screening. AB - Toxicology and pharmaceutical research is increasingly making use of high throughout-screening (HTS) methods to assess the effects of chemicals on molecular pathways, cells and tissues. Whole-genome microarray analysis provides broad information on the response of biological systems to chemical exposure, but is not practical to use when thousands of chemicals need to be evaluated at multiple doses and time points, as well as across different tissues, species and life-stages. A useful alternative approach is to identify a focused set of genes that can give a coarse picture of systems-level responses and that can be scaled to the evaluation of thousands of chemicals and diverse biological contexts. We demonstrate a computational approach to select in vitro expression assay targets that are informative and broadly distributed in biological pathway space, using the concept of pathway modularity. Canonical pathways are decomposed into subnetworks (modules) of functionally-related genes based on rules such as co regulated expression, protein-protein interactions, and coordinated physiological activity. Pathway modules are constructed using these rules but are then restricted by the bounds of canonical pathways. We demonstrate this approach using a subset of genes associated with tumor development and cancer progression. Target genes were identified for assay development, and then validated by using independent, published microarray data. The result is a targeted set of genes that are sensitive predictors of whether a chemical will perturb each pathway module. These selected genes could then form the basis for a battery to test for pathway-chemical interactions under many biological contexts using throughput expression-based assays. PMID- 22075578 TI - Molecular and ionic complexes of pyrrolidinofullerene bearing chelating 3-pyridyl units. AB - Molecular and ionic complexes of cis-2',5'-di(pyridin-3 yl)pyrrolidino[3',4':1,9](C(60)-I(h))[5,6]fullerene DP3FP with chlorobenzene (C(6)H(5)Cl), manganese(II) tetraphenylporphyrin (Mn(II)TPP) and tetrakis(dimethylamino)ethylene (TDAE) have been obtained for the first time. X ray single crystal structure determination for the crystalline DP3FP.C(6)H(5)Cl (1) solvate proved unambiguously its molecular structure with the cis-arrangement of chelating 3-pyridyl groups. It has been demonstrated that DP3FP easily forms self-assembled photoactive complexes with metallated porphyrins. For example, the formation of a 1 : 1 complex between DP3FP and zinc (II) tetraphenylporphyrin (Zn(II)TPP) in cyclohexane solution (2) was evidenced using absorption spectroscopy. A successful X-ray single crystal structure determination was performed for a self-assembled triad composed of a DP3FP molecule linked with two Mn(II)TPP molecules in {DP3FP.(Mn(II)TPP)(2)}.(C(6)H(4)Cl(2))(3) (3). A strong organic donor TDAE reduces DP3FP to the radical anion state thus forming an ionic complex (TDAE(+)).(DP3FP(-)).(C(6)H(4)Cl(2))(1.6) (4). Optical, electronic and magnetic properties of 4 were investigated in detail. The performed studies strongly suggest that pyrrolidinofullerene DP3FP can be used as a building block in the design of various organic materials with advanced optoelectronic and/or magnetic properties. PMID- 22075579 TI - Identification of non-diphtheriae corynebacterium by use of matrix-assisted laser desorption ionization-time of flight mass spectrometry. AB - We evaluated the Bruker Biotyper matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for identification of 92 clinical isolates of Corynebacterium species in comparison to identification using rpoB or 16S rRNA gene sequencing. Eighty isolates (87%) yielded a score of >=1.700, and all of these were correctly identified to the species level with the exception of Corynebacterium aurimucosum being misidentified as the closely related Corynebacterium minutissimum. PMID- 22075581 TI - Necrotizing fasciitis and septic shock related to the uncommon gram-negative pathogen Sphingobacterium multivorum. AB - We report the first case of necrotizing fasciitis due to the uncommon Gram negative pathogen Sphingobacterium multivorum in an immunocompromised patient, who presented with septic shock. This case adds necrotizing fasciitis to the spectrum of S. multivorum-related infections and highlights the emergence of Gram negative bacteria in severe soft tissue infections. PMID- 22075582 TI - Desulfovibrio desulfuricans bacteremia in an immunocompromised host with a liver graft and ulcerative colitis. AB - Desulfovibrio spp. are anaerobic, sulfate-reducing, nonfermenting, Gram-negative bacteria found in the digestive tract of humans. Identification of these species with conventional methods is difficult. The reported case of a Desulfovibrio desulfuricans bacteremia occurring in an immunocompromised host with ulcerative colitis confirms that this organism may be a possible opportunistic human pathogen. PMID- 22075580 TI - Delineation of Streptococcus dysgalactiae, its subspecies, and its clinical and phylogenetic relationship to Streptococcus pyogenes. AB - The taxonomic status and structure of Streptococcus dysgalactiae have been the object of much confusion. Bacteria belonging to this species are usually referred to as Lancefield group C or group G streptococci in clinical settings in spite of the fact that these terms lack precision and prevent recognition of the exact clinical relevance of these bacteria. The purpose of this study was to develop an improved basis for delineation and identification of the individual species of the pyogenic group of streptococci in the clinical microbiology laboratory, with a special focus on S. dysgalactiae. We critically reexamined the genetic relationships of the species S. dysgalactiae, Streptococcus pyogenes, Streptococcus canis, and Streptococcus equi, which may share Lancefield group antigens, by phylogenetic reconstruction based on multilocus sequence analysis (MLSA) and 16S rRNA gene sequences and by emm typing combined with phenotypic characterization. Analysis of concatenated sequences of seven genes previously used for examination of viridans streptococci distinguished robust and coherent clusters. S. dysgalactiae consists of two separate clusters consistent with the two recognized subspecies dysgalactiae and equisimilis. Both taxa share alleles with S. pyogenes in several housekeeping genes, which invalidates identification based on single-locus sequencing. S. dysgalactiae, S. canis, and S. pyogenes constitute a closely related branch within the genus Streptococcus indicative of recent descent from a common ancestor, while S. equi is highly divergent from other species of the pyogenic group streptococci. The results provide an improved basis for identification of clinically important pyogenic group streptococci and explain the overlapping spectrum of infections caused by the species associated with humans. PMID- 22075583 TI - Inaccuracy of the disk diffusion method compared with the agar dilution method for susceptibility testing of Campylobacter spp. AB - The agar dilution method has been standardized by the CLSI for the susceptibility testing of Campylobacter species, and according to these standards, the disk diffusion method should be used only in screening for macrolide and ciprofloxacin resistance. Nevertheless, the disk diffusion test is currently widely used, since it is easy to perform in clinical microbiology laboratories. In this study, the disk diffusion method was compared to the agar dilution method by analyzing the in vitro activities of seven antimicrobial agents against 174 Campylobacter strains collected in Finland between 2003 and 2008. Recommendations of the CLSI were followed using Mueller-Hinton agar plates with 5% of sheep blood. For each strain, the disk diffusion tests were performed two to four times. Of the 33 erythromycin-resistant strains (MIC, >=16 MUg/ml), 24 (73%) constantly showed a 6 mm erythromycin inhibition zone (i.e., no inhibition), while for seven strains the inhibition zone varied from 6 to 44 mm in repeated measurements. Among the 141 erythromycin-susceptible strains (MIC, <16 MUg/ml), erythromycin inhibition zones varied between 6 and 61 mm. Of the 87 ciprofloxacin-resistant strains, 47 (54%) showed 6-mm inhibition zones, while 40 strains showed inhibition zones between 6 and 60 mm. Significant differences between the repetitions were observed in the disk diffusion for all antimicrobial agents and all strains except for the macrolide-resistant strains regarding the macrolides. For 17 (10%) strains, the variation in repeated measurements was substantial. These results show that the disk diffusion method may not be a reliable tool for the susceptibility testing of Campylobacter spp. Further studies are needed to assess whether the disk diffusion test could be improved or whether all susceptibilities of campylobacters should be tested using an MIC-based method. PMID- 22075584 TI - Subtyping influenza A virus with monoclonal antibodies and an indirect immunofluorescence assay. AB - The recent association of certain influenza A virus subtypes with clinically relevant phenotypes has led to the increasing importance of subtyping by clinical virology laboratories. To provide clinical laboratories with a definitive immunofluorescence assay for the subtyping of influenza A virus isolates, we generated a panel of monoclonal antibodies (MAbs) against the major circulating influenza A virus subtypes using multiple inactivated H1N1, H3N2, and 2009 H1N1 strains individually as immunogens. Eleven MAbs that target hemagglutinin (HA) of H1N1 and H3N2 subtypes were selected. These MAbs were combined into three subtype specific reagents, one each for pan-H1 (seasonal and 2009 strains), H3, and 2009 H1, for the subtyping of influenza A virus-positive specimens by indirect immunofluorescence assay (IFA). Each subtype-specific reagent was tested on 21 prototype influenza A virus strains and confirmed to be specific for its intended subtype. In addition, the subtyping reagents did not cross-react with any of 40 other viruses. The clinical performance of the subtyping reagents was evaluated with 75 archived clinical samples collected between 2006 and 2009 using the D(3) Ultra DFA influenza A virus identification reagent (Diagnostic Hybrids, Inc., Athens, OH) and the influenza A virus subtyping reagents by IFA simultaneously. Sixty-four samples grew virus and were subtyped as follows: 30 as H3N2, 9 as seasonal H1N1, and 25 as 2009 H1N1. RT-PCR was used to confirm the influenza A virus subtyping of these samples, and there was 100% agreement with IFA. This subtyping IFA provides clinical laboratories with a cost-effective diagnostic tool for better management of influenza virus infection and surveillance of influenza virus activity. PMID- 22075585 TI - Use of a commercial PCR-based line blot method for identification of bacterial pathogens and the mecA and van genes from BacTAlert blood culture bottles. AB - In this study, the PCR-based DNA strip assay GenoType BC for the identification of bacteria and the resistance genes mecA, vanA, vanB, vanC1, and vanC2/3 directly from positive BacTAlert blood culture bottles was evaluated in a multicenter study. Of a total of 511 positive blood cultures, correct identification percentages for Gram-negative bacteria, Gram-positive bacteria, and the mecA gene were 96.1%, 89.9%, and 92.9%, respectively. Results were available 4 h after growth detection. PMID- 22075586 TI - Capnocytophaga lung abscess in a patient with metastatic neuroendocrine tumor. AB - Capnocytophaga species are known commensals of the oral cavity of humans and animals (mainly dogs and cats) and are a rare cause of respiratory tract infections. We report a case of cavitary lung abscess caused by a Capnocytophaga species in a patient with a metastatic neuroendocrine tumor. PMID- 22075587 TI - Human Mycobacterium bovis infections in London and Southeast England. AB - Variable-number tandem repeat (VNTR) and spoligotyping analyses were used to assess transmission of Mycobacterium bovis between humans. VNTR was more discriminatory than spoligotyping. Low case numbers, despite a substantial animal reservoir, and resolution of all isolates provided no evidence of recent human-to human transmission or recent significant infection from animals. PMID- 22075588 TI - Polyclonal diffusion of beta-lactamase-producing Enterococcus faecium. AB - We describe here the isolation of 8 beta-lactamase-producing multidrug-resistant Enterococcus faecium isolates in 2010. All strains showed diverse pulsed-field gel electrophoresis (PFGE) profiles, all belonging to the same clonal complex, CC17. By PCR and hybridization experiments, the entire blaZ-blaI-blaR1 operon was found. The beta-lactamase activity was demonstrated at a high inoculum and in the presence of methicillin after overnight incubation. PMID- 22075589 TI - Clostridium difficile mixed infection and reinfection. AB - Isolates from consecutive Clostridium difficile infection (CDI) fecal samples underwent multilocus sequence typing. Potential reinfections with different genotypes were identified in 88/560 (16%) sample pairs taken 1 to 1,414 days (median, 24; interquartile range [IQR], 1 to 52 days) apart; odds of reinfection increased by 58% for every doubling of time between samples. Of 109 sample pairs taken on the same day, 3 (3%) had different genotypes. Considering samples 0 to 7 days apart as the same CDI, 7% of cases had mixed infections with >1 genotype. PMID- 22075590 TI - Highly specific protease-based approach for detection of porphyromonas gingivalis in diagnosis of periodontitis. AB - Porphyromonas gingivalis is associated with the development of periodontitis. Here we describe the development of a highly specific protease-based diagnostic method for the detection of P. gingivalis in gingival crevicular fluid. Screening of a proteolytic peptide substrate library, including fluorogenic dipeptides that contain d-amino acids, led to the discovery of five P. gingivalis-specific substrates. Due to the presence of lysine and arginine residues in these substrates, it was hypothesized that the cleavage was mediated by the gingipains, a group of P. gingivalis-specific proteases. This hypothesis was confirmed by the observation that P. gingivalis gingipain knockout strains demonstrated clearly impaired substrate cleavage efficacy. Further, proteolytic activity on the substrates was increased by the addition of the gingipain stimulators dithiothreitol and l-cysteine and decreased by the inhibitors leupeptin and N ethylmaleimide. Screening of saliva and gingival crevicular fluid of periodontitis patients and healthy controls showed the potential of the substrates to diagnose the presence of P. gingivalis proteases. By using paper points, a sensitivity of approximately 10(5) CFU/ml was achieved. P. gingivalis reactive substrates fully composed of l-amino acids and Bz-l-Arg-NHPhNO(2) showed a relatively low specificity (44 to 85%). However, the five P. gingivalis specific substrates that each contained a single d-amino acid showed high specificity (96 to 100%). This observation underlines the importance of the presence of d-amino acids in substrates used for the detection of bacterial proteases. We envisage that these substrates may improve the specificity of the current enzyme-based diagnosis of periodontitis associated with P. gingivalis. PMID- 22075591 TI - Evaluation of Neisseria gonorrhoeae multiple-locus variable-number tandem-repeat analysis, N. gonorrhoeae Multiantigen sequence typing, and full-length porB gene sequence analysis for molecular epidemiological typing. AB - The performance characteristics of Neisseria gonorrhoeae multilocus variable number tandem-repeat analysis were evaluated, by comparison with N. gonorrhoeae multiantigen sequence typing and full-length porB sequence typing. Assessment of the relatedness of intra- and interpatient isolates showed that all three genotyping techniques display a high resolution and typeability. PMID- 22075592 TI - Comparison of the cobas Human Papillomavirus (HPV) test with the hybrid capture 2 and linear array HPV DNA tests. AB - The cobas human papillomavirus (HPV) test (cobas) was recently approved by the U.S. Food and Drug Administration (FDA) and identifies HPV16 and HPV18 separately as well as detecting a pool of 11 HR-HPV genotypes (HPV31, -33, -35, -39, -45, 51, -52, -56, -58, -59, -68) and also HPV66. We compared cobas, Linear Array (LA), and Hybrid Capture 2 (HC2) assays for detection of carcinogenic HPV DNA, and cobas and LA for detection of HPV16 and HPV18 DNA, among the first 1,852 women enrolled in the HPV Persistence and Progression Cohort (PaP Cohort) study. Specimens were tested by all 3 assays 1 year after an HC2-positive result. In 1,824 specimens with cobas results, cobas had an 85.9% agreement with HC2 and 91.0% agreement with LA for carcinogenic HPV detection. When results between cobas and HC2 disagreed, cobas tended to call more women HPV positive (P < 0.01). Categorizing cobas and LA results hierarchically according to cancer risk (HPV16, HPV18, other carcinogenic HPV genotypes, or carcinogen negative), there was a 90% agreement for all categories of HPV (n = 1,824). We found good agreement between the two U.S. FDA-approved HPV tests, with discrepancies between the two assays due to specific characteristics of the individual assays. Additional studies are needed to compare HC2 and cobas for detecting and predicting CIN3 to understand the clinical implications of the discrepant test results between the two tests. PMID- 22075594 TI - A longitudinal case series description of meningitis due to Streptococcus gallolyticus subsp. pasteurianus in infants. AB - Streptococcus gallolyticus subsp. pasteurianus, previously known as Streptococcus bovis biotype II.2, is known to cause multiple infectious complications, including bacterial meningitis, in adults. Only sporadic individual case reports have identified this pathogen as a cause of meningitis in infants. This study is the first to longitudinally document S. gallolyticus subsp. pasteurianus as a cause of meningitis in four epidemiologically unrelated infants less than 2 weeks of age. The 16S rRNA gene sequences of all 4 isolates were identical, and further were identical to 3 central nervous system (CNS) strains (two adults and one child) reported in existing literature. S. gallolyticus subsp. pasteurianus is an increasingly recognized cause of meningitis and bacteremia in the newborn period, and it merits further study with respect to etiology of infection. PMID- 22075595 TI - Clinical impact of a real-time PCR assay for rapid identification of staphylococcal bacteremia. AB - The purpose of this study was to evaluate the impact of real-time PCR reporting both on timely identification of clustered Gram-positive cocci (GPC) in blood cultures and on appropriate antibiotic treatment. This retrospective, interventional cohort study evaluated inpatients with blood cultures positive for GPC in the pre-PCR (15 January 2009 to 14 January 2010) and post-PCR (15 January 2010 to 14 January 2011) periods. Post-PCR implementation, laboratory services completed batched PCR; results other than methicillin-resistant Staphylococcus aureus (MRSA) were reported in the electronic medical record without additional interventions. The assay's sensitivity and specificity, time to identification of staphylococcal bacteremia, and clinically relevant outcomes, including time to optimal antibiotic therapy, were evaluated. Demographic information was also collected and analyzed. Sixty-eight and 58 patients with Staphylococcus aureus bacteremia from the pre- and post-PCR periods, respectively, met inclusion criteria. Similar numbers of consecutive patients with coagulase-negative staphylococci were analyzed for comparison. The time to identification was significantly reduced post-PCR implementation (mean, 13.2 h; 95% confidence interval [95% CI], 10.5 to 15.9 h; P < 0.0001). However, the time to optimal antibiotic therapy was not significantly reduced. We conclude that implementation of a PCR assay demonstrated the potential to improve appropriate antibiotic use based on clinically meaningful and statistically significant reductions in the time to microbiologic identification. However, in order to realize this potential benefit, processes must be optimized and additional interventions initiated to facilitate providers' use of the PCR result. PMID- 22075593 TI - Diagnostic accuracy of serum 1,3-beta-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. AB - Serum 1,3-beta-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP. PMID- 22075596 TI - Simultaneous detection of six diarrhea-causing bacterial pathogens with an in house PCR-luminex assay. AB - Diarrhea can be caused by a range of pathogens, including several bacteria. Conventional diagnostic methods, such as culture, biochemical tests, and enzyme linked immunosorbent assay (ELISA), are laborious. We developed a 7-plex PCR Luminex assay to simultaneously screen for several of the major diarrhea-causing bacteria directly in fecal specimens, including pathogenic Aeromonas, Campylobacter jejuni, Campylobacter coli, Salmonella, Shigella, enteroinvasive Escherichia coli (EIEC), Vibrio, and Yersinia. We included an extrinsic control to verify extraction and amplification. The assay was first validated with reference strains or isolates and exhibited a limit of detection of 10(3) to 10(5) CFU/g of stool for each pathogen as well as quantitative detection up to 10(9) CFU/g. A total of 205 clinical fecal specimens from individuals with diarrhea, previously cultured for enteric pathogens and tested for Campylobacter by ELISA, were evaluated. Using these predicate methods as standards, sensitivities and specificities of the PCR-Luminex assay were 89% and 94% for Aeromonas, 89% and 93% for Campylobacter, 96% and 95% for Salmonella, 94% and 94% for Shigella, 92% and 97% for Vibrio, and 100% and 100% for Yersinia, respectively. All discrepant results were further examined by singleplex real time PCR assays targeting different gene regions, which revealed 89% (55/62 results) concordance with the PCR-Luminex assay. The fluorescent signals obtained with this approach exhibited a statistically significant correlation with the cycle threshold (C(T)) values from the cognate real-time PCR assays (P < 0.05). This multiplex PCR-Luminex assay enables sensitive, specific, and quantitative detection of the major bacterial causes of gastroenteritis. PMID- 22075598 TI - Evaluation of rapid antigen point-of-care tests for detection of Giardia and Cryptosporidium species in human fecal specimens. AB - In Bangladesh, a new parasite rapid antigen test was investigated demonstrating accuracy and feasibility. For Giardia species, it had a sensitivity and specificity of 94% and 100%, respectively. For Cryptosporidium species, it had a sensitivity and specificity of 100% and 100%, respectively. These are higher than or equal to the sensitivities and specificities of other tests on the market. PMID- 22075597 TI - GenoType MTBDRsl for molecular detection of second-line-drug and ethambutol resistance in Mycobacterium tuberculosis strains and clinical samples. AB - The purpose of this study was to evaluate the GenoType MTBDRsl assay (Hain Lifescience GmbH, Nehren, Germany) for its ability to detect resistance to fluoroquinolones (FLQ), injectable second-line antibiotics [kanamycin (KM) and capreomycin (CM)], and ethambutol (EMB) in Mycobacterium tuberculosis clinical strains and directly in clinical samples. A total of 34 clinical strains were characterized with the Bactec 460 TB system. Fifty-four clinical samples from 16 patients (5 were smear negative and 49 were smear positive) were also tested directly. The corresponding isolates of the clinical specimens were also analyzed with the Bactec 460TB. When there was a discrepancy between assays, pyrosequencing was performed. The overall rates of concordance of the MTBDRsl and the Bactec 460TB for the detection of FLQ, KM/CM, and EMB susceptibility in clinical strains were 72.4% (21/29), 88.8% (24/27), and 67.6% (23/34), whereas for clinical samples, rates were 86.5% (45/52), 92.3% (48/52), and 56% (28/50), respectively. In conclusion, the GenoType MTBDRsl assay may be a useful tool for making early decisions regarding KM/CM susceptibility and to a lesser extent regarding FLQ and EMB susceptibility. The test is able to detect mutations in both clinical strains and samples with a short turnaround time. However, for correct management of patients with extensively drug-resistant tuberculosis, results must be confirmed by a phenotypical method. PMID- 22075599 TI - Identification of Escherichia coli genes associated with urinary tract infections. AB - Escherichia coli is the most common cause of urinary tract infections (UTIs). E. coli genes epidemiologically associated with UTIs are potentially valuable in developing strategies for treating and/or preventing such infections as well as differentiating uropathogenic E. coli from nonuropathogenic E. coli. To identify E. coli genes associated with UTIs in humans, we combined microarray-based and PCR-based analyses to investigate different E. coli source groups derived from feces of healthy humans and from patients with cystitis, pyelonephritis, or urosepsis. The cjrABC-senB gene cluster, sivH, sisA, sisB, eco274, and fbpB, were identified to be associated with UTIs. Of these, cjrABC-senB, sisA, sisB, and fbpB are known to be involved in urovirulence in the mouse model of ascending UTI. Our results provide evidence to support their roles as urovirulence factors in human UTIs. In addition, the newly identified UTI-associated genes were mainly found in members of phylogenetic groups B2 and/or D. PMID- 22075600 TI - Antifungal susceptibility and phylogeny of opportunistic members of the order mucorales. AB - The in vitro susceptibilities of 66 molecularly identified strains of the Mucorales to eight antifungals (amphotericin B, terbinafine, itraconazole, posaconazole, voriconazole, caspofungin, micafungin, and 5-fluorocytosine) were tested. Molecular phylogeny was reconstructed based on the nuclear ribosomal large subunit to reveal taxon-specific susceptibility profiles. The impressive phylogenetic diversity of the Mucorales was reflected in susceptibilities differing at family, genus, and species levels. Amphotericin B was the most active drug, though somewhat less against Rhizopus and Cunninghamella species. Posaconazole was the second most effective antifungal agent but showed reduced activity in Mucor and Cunninghamella strains, while voriconazole lacked in vitro activity for most strains. Genera attributed to the Mucoraceae exhibited a wide range of MICs for posaconazole, itraconazole, and terbinafine and included resistant strains. Cunninghamella also comprised strains resistant to all azoles tested but was fully susceptible to terbinafine. In contrast, the Lichtheimiaceae completely lacked strains with reduced susceptibility for these antifungals. Syncephalastrum species exhibited susceptibility profiles similar to those of the Lichtheimiaceae. Mucor species were more resistant to azoles than Rhizopus species. Species-specific responses were obtained for terbinafine where only Rhizopus arrhizus and Mucor circinelloides were resistant. Complete or vast resistance was observed for 5-fluorocytosine, caspofungin, and micafungin. Intraspecific variability of in vitro susceptibility was found in all genera tested but was especially high in Mucor and Rhizopus for azoles and terbinafine. Accurate molecular identification of etiologic agents is compulsory to predict therapy outcome. For species of critical genera such as Mucor and Rhizopus, exhibiting high intraspecific variation, susceptibility testing before the onset of therapy is recommended. PMID- 22075601 TI - The beginning of the rpoB gene in addition to the rifampin resistance determination region might be needed for identifying rifampin/rifabutin cross resistance in multidrug-resistant Mycobacterium tuberculosis isolates from Southern China. AB - We aimed to study the distribution and contribution of mutations in the rpoB whole gene in rifampin-resistant/rifabutin-resistant (RIF(r)/Rfb(r)) (or RIF/Rfb cross-resistant) clinical Mycobacterium tuberculosis isolates. One standard M. tuberculosis strain (H37Rv) and 392 other clinical M. tuberculosis isolates mainly from Guangdong Province of China whose susceptibilities to rifampin (RIF), rifabutin (Rfb), streptomycin (SM), ethambutol (EMB), and isoniazid (INH) were previously determined were subjected to DNA sequencing of their rpoB whole genes. H37Rv and the 30 drug-susceptible clinical isolates had no mutations in rpoB whole genes. In 43 rifampin-resistant/rifabutin-susceptible (RIF(r)/Rfb(s)) isolates, the most frequent mutation codons were 516 (62.80%), 526 (14.0%), and 533 (6.98%), but codon 531 had no mutation. Twenty-one of the 43 isolates (48.84%) had single mutations of H526L, H526S, D516V, D516Y, and D516F. In 319 RIF(r)/Rfb(r) isolates, the most frequent mutation codons were 531 (73.7%) and 526 (18.8%); the mutation frequency for codon 516 was 2.5%, and that for codon 533 was only 0.31%. A total of 82.8% (264/319) of them had single mutations of S531L, S531W, H526D, H526Y, H526R, Q513K, Q513P, Q510H, V176F, P206(T)R, Y314(T)C, and H323(T)Y (the superscript T indicates M. tuberculosis numbering; the remaining codons use the E. coli numbering), among which V176F, P206(T)R, Y314(T)C, and H323(T)Y were located in the beginning of rpoB, and all of them were present in 1.9% (6/319) of RIF(r)/Rfb(r) isolates. The multiple mutations in RIF(r)/Rfb(r) isolates and in RIF(r)/Rfb(s) isolates were also different from each other either in mutation positions or in types of mutation combinations. In conclusion, the mutations of rpoB in RIF-R/Rfb(s) and in RIF-R/Rfb-R isolates differ significantly from each other not only in the most frequent mutation codons (516, 531, and 533) but also in the most frequent single mutations (S531L, H526L, D516V, D516Y, and D516F), and the beginning of rpoB may confer a RIF/Rfb cross-resistance phenotype in M. tuberculosis. Molecular assays for identifying RIF/Rfb cross-resistance in M. tuberculosis might be improved in terms of accuracy by including this region, in addition to the rifampin resistance determination region. PMID- 22075602 TI - Estimates of HIV transmitted drug resistance can be inflated due to natural sequence polymorphisms. PMID- 22075603 TI - Should we switch to a 50-mg boosting dose of ritonavir for selected protease inhibitors? PMID- 22075604 TI - HIV counseling and testing in an urban reproductive primary health clinic in South Africa: gender differences among clients. PMID- 22075605 TI - Clinical significance of serum levels of secretory leukocyte protease inhibitor in patients with systemic sclerosis. AB - We aimed to investigate the clinical significance of serum levels of secretory leukocyte protease inhibitor (SLPI), which is widely expressed in lung tissues and serves as a useful marker reflecting the activity of various lung diseases, in patients with systemic sclerosis (SSc). Serum SLPI levels were measured by a specific enzyme-linked immunosorbent assay (ELISA) in 58 SSc patients and 16 healthy controls. Serum SLPI levels in diffuse cutaneous SSc and in limited cutaneous SSc with interstitial lung disease (ILD) were significantly higher than those in healthy controls (43.1 +/- 18.4 vs. 30.9 +/- 3.76 ng/ml, p < 0.05 and 39.8 +/- 10.3 vs. 30.9 +/- 3.76 ng/ml, p < 0.01, respectively). The incidences of decreased percent diffusing capacity for carbon monoxide (%DLco) and decreased percent vital capacity (%VC) were significantly greater in SSc patients with elevated SLPI levels than in those with normal levels (73 vs. 31%, p < 0.01 and 24 vs. 4%, p < 0.05, respectively). Furthermore, serum SLPI levels were inversely correlated with %DLco (r = -0.40, p < 0.01), while they were positively correlated with surfactant protein D (r = 0.28, p < 0.05). Longitudinal study revealed the association of serum SLPI levels with the disease activity of SSc ILD. SLPI serves as a useful serum marker for evaluating SSc-ILD. PMID- 22075606 TI - [Initial division of the left renal vein before dissection of left renal vein occluded by intracaval tumor thrombus]. AB - Between November 2008 and March 2010, we performed initial division of the left renal vein occluded by the tumor thrombus in six cases of left renal cancer at Toranomon Hospital. The left renal vein was completely occluded by the tumor thrombus in all cases. In order to ligate the left renal artery first behind the dilated left renal vein, we must dissect the left kidney with arterial blood flow. Massive bleeding from the numerous engorged collateral veins around the left kidney is inevitable. Furthermore, access to the left renal artery is difficult because of the large tumor. We therefore initially divided the left renal vein without arterial blood flow followed by division of the left renal artery. After nephrectomy by dissecting the tumor without blood flow we extirpated the intracaval tumor thrombus. The median time of the operation was 7 hours 35 minutes and the median amount of blood loss was 2,869 ml. The tumor stage was pT3b in four cases and pT3c in two cases. No complications were observed during and after surgery except for one case of lymphocele and another case of chylous ascites. The initial division of the left renal vein is considered to be a useful surgical approach in left renal cancer with occluded left renal vein, especially when the tumor is large. PMID- 22075607 TI - [Docetaxel-based chemotherapy for hormone-refractory prostate cancer in Japanese patients : experience in a single institute]. AB - Between April 2007 and November 2010, we treated 21 cases of hormone-refractory prostate cancer with docetaxel-based chemotherapy. The administered dose of docetaxel was from 40 to 75 mg/m2, and the treatments were repeated every 3 to 4 weeks. The patients were from 61 to 88 years old (median 78). Fourteen patients were alive, and seven had died. According to the prostate specific antigen response, the complete response rate was 30%, partial response was 10%, no change was 25%, and progressive disease was 25%, respectively. Median time to progression was 7.0 months (from 1 to 43 months), and median overall survival time after chemotherapy was 11.5 months (from 3 to 44 months). One patient died of adverse events. However, in most cases, hematological toxicities were tolerable and manageable, although neutropenia of grade 3 to 4 was observed. On the other hand, non-hematological toxicities that led to discontinuation of the therapy were observed in a few cases. Docetaxel-based chemotherapy was feasible and effective even for patients over 80 years old. In responding cases, it is important to maintain the chemotherapy as long as possible, by modifying the treatment procedures, while paying attention to the adverse events. PMID- 22075608 TI - [Clinical outcome of refractory seminoma]. AB - We retrospectively reviewed 67 patients with pure seminoma who were treated in our hospital between 1991 and 2009. Fifteen (22.4%) patients had metastatic or recurrent disease and underwent chemotherapy. Induction chemotherapy provided freedom from disease with no recurrence in 9 patients. On the other hand, 6 patients had chemotherapy-resistant seminoma (refractory group). We herein report the clinical features of the refractory group. Although we could not determine the risk factors for refractory disease, clinical stage III disease was resistant to induction chemotherapy. The refractory group consisted of 2 patients with recurrent disease after prophylactic radiation therapy for stage I disease, 1 with stage IIB and 3 with stage IIIC disease. In the refractory group, 3 patients obtained freedom from disease after additional chemotherapy with salvage surgery. However, 3 patients died from cancer in spite of multiple salvage treatments. Salvage radiation therapy was performed for inoperable metastatic disease in 3 patients and might have contributed to disease control in 2 patients. Some patients with pure seminoma can develop refractory disease, although the prediction is difficult. Multimodality therapy including salvage radiation possibly provides survival benefit. PMID- 22075609 TI - [Laparoscopic resection of retroperitoneal schwannoma : report of three cases and review of 22 cases in Japanese literature]. AB - Retroperitoneal schwannoma is a rare tumor. Only 19 cases have been reported to be treated by laparoscopic surgery. We performed successful laparoscopic excision of retroperitoneal schwannoma using the four-trocar in three patients who had a left retroperitoneal mass. The patients were two women and one man. They were 62, 60 and 57 years old. The tumor was 70, 45 and 50 mm in greatest diameter and operative time was 204, 243 and 254 min. respectively. The pathological diagnosis of the tumor was schwannoma. There was no morbidity or mortality. Preoperative diagnosis of schwannoma is very difficult. However schwannoma is a benign tumor with a good prognosis. This laparoscopic excision for retroperitoneal schwannoma is effective and rather safe. PMID- 22075610 TI - [Small renal cell carcinoma presented with pleural metastasis and multiple bone metastasis ; a case report]. AB - The patient is a 69-year-old male. His chief complaint was chest pain. Because imaging studies suggested pleural mesothelioma associated with multiple bone metastases, right pleural tumor resection was performed. Pathological diagnosis was metastatic pleural tumor, and renal cell carcinoma (RCC) was suspected as its origin. Dynamic computed tomography showed a small tumor in the right kidney. The tumor was 15 mm in diameter and consistent with RCC. Laparoscopic radical nephrectomy was performed for the right kidney. Pathological diagnosis was RCC, clear cell carcinoma with sarcomatoid component, T1aN0M1, stage IV. Sorafenib therapy was started 46 days after the operation as a systemic therapy, and stable disease has been maintained. Generally, small RCC is assumed to have a good prognosis. However, a small percentage of patients with small RCC have distant metastasis at the time of diagnosis, and the prognosis is reported to be poor. We report this case, and a review of the literature. PMID- 22075611 TI - [Infected solitary renal cyst of the graft in a renal transplant recipient : a case report]. AB - A 59-year-old woman with end-stage renal disease of diabetic nephropathy who had been on maintenance hemodialisis for 4 years, underwent a living-unrelated renal transplantation 6 years ago. She was admitted to our hospital, because of a low grade fever and edema. Ultrasonography revealed the cyst with heterogeneity structure in the upper pole of the transplanted kidney. Magnetic resonance imaging showed a high-intensity cystic mass measuring 68*53 mm. As fever and laboratory data did not improve sufficiently by the treatment with antibiotics, echo-guided puncture and drainage were performed for the abnormal structure in the upper pole of the transplanted kidney. In the culture of the purulent aspirate drained from renal cyst, Escherichia coli was isolated. To our knowledge, this is the first report of infected renal cyst of the graft in a renal transplant recipient in the world. PMID- 22075612 TI - [A case report of small intestine metastasis from renal cell carcinoma]. AB - A 71-year-old man underwent left nephrectomy for metastasis from renal cell carcinoma (RCC) of the small intestine. In spite of post-operative therapy (interferon-alpha or interleukin-2), multiple lung metastases and intestinal hemorrhage by metastatic tumor of small intestine appeared 9 years after the operation. To control the bleeding from the small intestine, the small intestine was partially excised and the histopathological diagnosis was metastasis of RCC. He died 10 months later because of disease progression. Metastasis of RCC to the small intestine is rare. To our knowledge, this is the 40th case of small intestinal metastasis from RCC reported in the literature. PMID- 22075613 TI - [Bilateral upper tract urothelial carcinoma eight years after total cystectomy and Indiana pouch urinary diversion for bladder cancer : a case report]. AB - A 46-year-old man underwent total cystectomy and Indiana pouch urinary diversion for bladder cancer in 2001. Pathological examination revealed an urothelial carcinoma of the bladder (pT2N0M0). He was referred to our hospital for bilateral hydronephrosis in June 2009. Cytological examination of the urine was negative. Percutaneous nephrostomy was performed, and we suspected bilateral ureteral tumors from pyelo-ureterography. Percutaneous ureteroscopy revealed a papillary tumor in the right ureter. Since there appeared to be a papillary tumor in the left ureter, we decided to perform ureterectomy for bilateral ureteral tumors, and to keep the bilateral nephrostomy tube for urinary diversion. Pathological examination revealed urothelial carcinoma in bilateral ureters. There has been no sign of recurrence at 17 months after the operation. PMID- 22075614 TI - [Intravesical therapy of heparin and lidocaine for interstitial cystitis : a case report]. AB - Interstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder, and its treatment has many uncertainties. We report a case of IC treated with intravesical instillation of heparin and alkalized lidocaine. A 64-year-old woman presented with urinary frequency and urgency with suprapubic pain. She underwent intravesical treatment with combined heparin and alkalinized lidocaine for IC, since prior medical treatments (imipramine, solifenacin, suplatast tosilate, and kampo extracts) and hydrodistention of bladder had little or no effect on her symptoms. A 50 ml solution containing 20,000 units of heparin, 200 mg of lidocaine and 7% sodium bicarbonate was administered intravesically twice a week for 12 months. The O'Leary-Sant IC symptom index score and IC problem index score improved from 20 to 8 and from 16 to 8, respectively, and her bladder capacity increased from 90 ml to 300 ml. Intravesical instillation of combined heparin and lidocaine was useful in the treatment of IC. PMID- 22075615 TI - [A case of solitary bone metastasis of testicular seminoma 6 years post orchiectomy]. AB - A 40-year-old man visited our hospital in August, 2007 with the complaint of gait disturbance. Six years ago he had had right high orchiectomy for treatment of stage I seminoma at another hospital. The magnetic resonance imaging (MRI) examination showed a small tumor and compression fracture in the eighth thoracic vertebrae. Emergency spinal decompression with bone biopsy was done. The pathological diagnosis of the bone was metastasis of seminoma. He was treated with 3 courses of BEP (bleomycin, etoposide and cisplatin) therapy and external beam radiotherapy (36 Gy) was performed. His symptom of gait disturbance disappeared gradually, and was evaluated to be in complete remission. He has been alive with no evidence of recurrence for 3 years. PMID- 22075616 TI - [Leydig cell tumor of the testis : a case report]. AB - An 85-year-old male visited our hospital with a complaint of painless swelling of the right testis. Right high orchiectomy was performed under the diagnosis of the right testicular tumor. Histopathological diagnosis was Leydig cell tumor. We reviewed 86 cases of this tumor previously reported in Japan. To our knowledge, our patient is the oldest one treated in Japan. PMID- 22075617 TI - [A case report of bilateral spermatocytic seminoma]. AB - Spermatocytic seminoma is a rare germ cell tumor which was first described by Masson in 1946. We experienced a case of bilateral spermatocytic seminoma. A 56 year-old man presented with painless swelling of left scrotal contents. This patient was diagnosed with bilateral testicular tumor after various image examinations (ultrasonography/computerized tomography/magnetic resonance imaging) and bilateral high orchidectomy was performed. Histological diagnosis was bilateral spermatocytic seminoma, pT1. After the operation, this patient was followed closely without adjuvant therapy. There has been no sign of recurrence at five months after the operation. PMID- 22075618 TI - [Successful testicular sperm extraction in an azoospermic man with postpubertal mumps orchitis]. AB - A 46-year-old man who has a child from a previous marriage without artificial reproductive technologies was referred to our hospital with a chief complaint of infertility. He had suffered from bilateral orchitis after parotitis six years ago. On physical examination, both testes were soft and 4 ml in size. Semen analysis showed azoospermia and the serum follicle stimulating hormone value was high (36.9 mIU/ml). Microdissection testicular sperm extraction was performed, and motile sperm were successfully retrieved. The histological examination showed increased thickness of the basement membrane and, peritubular fibrosis in most seminiferous tubules, with few focal areas of normal spermatogenesis. PMID- 22075619 TI - Role of a computer-generated three-dimensional laryngeal model in anatomy teaching for advanced learners. AB - OBJECTIVES: (1) To investigate the efficacy of a computer-generated three dimensional laryngeal model for laryngeal anatomy teaching; (2) to explore the relationship between students' spatial ability and acquisition of anatomical knowledge; and (3) to assess participants' opinion of the computerised model. SUBJECTS AND METHODS: Forty junior doctors were randomised to undertake laryngeal anatomy study supplemented by either a three-dimensional computer model or two dimensional images. Outcome measurements comprised a laryngeal anatomy test, the modified Vandenberg and Kuse mental rotation test, and an opinion survey. RESULTS: Mean scores +/- standard deviations for the anatomy test were 15.7 +/- 2.0 for the 'three dimensions' group and 15.5 +/- 2.3 for the 'standard' group (p = 0.7222). Pearson's correlation between the rotation test scores and the scores for the spatial ability questions in the anatomy test was 0.4791 (p = 0.086, n = 29). Opinion survey answers revealed significant differences in respondents' perceptions of the clarity and 'user friendliness' of, and their preferences for, the three-dimensional model as regards anatomical study. CONCLUSION: The three dimensional computer model was equivalent to standard two-dimensional images, for the purpose of laryngeal anatomy teaching. There was no association between students' spatial ability and functional anatomy learning. However, students preferred to use the three-dimensional model. PMID- 22075620 TI - Correlation of PU.1 and signal regulatory protein alpha1 expression in PU.1 transgenic K562 cells. AB - PU.1 is a key transcription factor for hematopoiesis and the reduction of this protein expression plays important roles in various hematological malignancies. To identify PU.1 downstream target genes, we recently reported dual microarray analyses, using PU.1 knockdown K562 (K562PU.1KD) cells stably expressing short inhibitory RNAs versus control cells and PU.1-overexpressing K562 (K562PU.1OE) cells versus control cells. Several PU.1 candidate target genes, including cell surface receptor, signal regulatory protein (SIRP) alpha1, were identified. In this study, we revealed that the expression of SIRPalpha1 is positively correlated with the expression of PU.1 in various K562PU.1KD and K562PU.1OE cells, shown by real-time PCR and flow cytometry analyses. SIRPalpha1 is a negative regulator of signaling and its reduced expression is considered to play a role in the pathogenesis of hematological malignancies through the activation of downstream signaling pathways. By comparing 3 different clones of K562PU.1KD cells to their controls, we found constitutive phosphorylation of the extracellular signal-regulated kinase (ERK), but not of Akt, in these cells. Taken together, the down-regulation of PU.1 expression suppresses the expression of SIRPalpha1, which may play a role in the aberrant activation of ERK in these cells. PMID- 22075621 TI - Stridor and lingual thyroglossal duct cyst in a newborn. AB - OBJECTIVE: To describe the diagnosis and management of lingual thyroglossal duct cyst in newborns. CASE REPORT: A one-month-old girl presenting with inspiratory stridor and chest wall retraction was referred to our department for management of stridor. Upper airway endoscopy and neck CT scan showed a round mass at the base of the tongue causing upper airway obstruction. Computed tomography showed a well-circumscribed, low-density lesion at the base of the tongue. Endoscopic marsupialization of this lesion was performed under general anaesthesia. Histological examination confirmed the diagnosis of lingual thyroglossal duct cyst. No recurrence was observed 18 months after endoscopic treatment. DISCUSSION/CONCLUSION: Lingual thyroglossal duct cyst with airway obstruction is an uncommon aetiology of stridor in newborns with symptoms similar to those of laryngomalacia. The diagnosis is based on laryngoscopy. Surgical endoscopic removal is the treatment of choice. Recurrence after endoscopic treatment is rare. PMID- 22075622 TI - Human choriocarcinomas: placental growth factor-dependent preclinical tumor models. AB - Choriocarcinomas are a rare form of cancer that develops in the uterus from tissue which would normally become the placenta. Choriocarcinomas are a trophoblastic gestational disease and have been studied largely to investigate conditions related to pregnancy such as preeclampsia. Choriocarcinomas are highly angiogenic and produce high levels of placental growth factor (PlGF) to promote the development of blood vessels. Upregulation of PlGF expression also occurs during the development of other human malignancies such as breast cancer and melanoma. Both tumor specimens and plasma samples have higher levels of PlGF than normal tissues. Hence, PlGF has emerged as a valid target for anti-angiogenic therapy. The cell lines BeWo, JAR and JEG-3, derived from human choriocarcinomas, were investigated in vitro and in vivo for suitability as PlGF-dependent models. BeWo, JAR and JEG-3 cells were characterized in culture and were implanted into immunodeficient mice to generate subcutaneous tumors. The PlGF and VEGF angiogenic profiles of the choriocarcinoma cells and tumors were investigated by ELISA and by immunohistochemical methods. Double immunofluorescence methods were applied to choriocarcinoma xenograft sections to characterize the cellular components of the blood vessels. sFLT01, a fusion protein that neutralizes PlGF, was assessed in cell culture experiments and xenograft studies. The novel results presented here validate the importance of human choriocarcinoma cell lines and xenografts in further exploring the role of PlGF in tumor angiogenesis, for evaluating PlGF as an anti-angiogenic target, and for developing therapies that may provide clinical benefit. PMID- 22075624 TI - Evaluation of methods for the extraction of DNA from drinking water distribution system biofilms. AB - While drinking water biofilms have been characterized in various drinking water distribution systems (DWDS), little is known about the impact of different DNA extraction methods on the subsequent analysis of microbial communities in drinking water biofilms. Since different DNA extraction methods have been shown to affect the outcome of microbial community analysis in other environments, it is necessary to select a DNA extraction method prior to the application of molecular tools to characterize the complex microbial ecology of the DWDS. This study compared the quantity and quality of DNA yields from selected DWDS bacteria with different cell wall properties using five widely used DNA extraction methods. These were further selected and evaluated for their efficiency and reproducibility of DNA extraction from DWDS samples. Terminal restriction fragment length analysis and the 454 pyrosequencing technique were used to interpret the differences in microbial community structure and composition, respectively, from extracted DNA. Such assessments serve as a concrete step towards the determination of an optimal DNA extraction method for drinking water biofilms, which can then provide a reliable comparison of the meta-analysis results obtained in different laboratories. PMID- 22075626 TI - Intestinal adenocarcinoma arising in urinary conduits. AB - It is estimated that >10,000 patients who undergo cystectomy for bladder cancer in the US each year receive a conventional ileal conduit and that >2,000 receive a continent urinary diversion. Case reports of primary intestinal adenocarcinomas in urinary conduits have been published recently, mainly in the urology literature. An epidemic of such cancers in this small, high-risk population seems to be emerging, particularly in conduits that utilize the colon. A case report and literature review was carried out. We describe a patient with a new primary adenocarcinoma arising in a colonic neobladder. We summarize prior literature describing intestinal adenocarcinomas that developed in an intestinal segment used for urinary diversion. Patients with urinary conduits of all types (particularly those utilizing colon rather than ileum) are at high risk of developing a second primary intestinal adenocarcinoma in the conduit. This population is likely to benefit from surveillance measures aimed at detecting such cancers. The primary form of therapy remains adequate surgical resection. General surgeons should be aware of such patients as they may be involved in the diagnosis of, and surgery for, the cancer in the conduit. PMID- 22075625 TI - Comparison among amoA primers suited for quantification and diversity analyses of ammonia-oxidizing bacteria in soil. AB - Ammonia monooxygenase subunit A gene (amoA) is frequently used as a functional gene marker for diversity analysis of ammonia-oxidizing bacteria (AOB). To select a suitable amoA primer for real-time PCR and PCR-denaturing gradient gel electrophoresis (DGGE), three reverse primers (degenerate primer amoA-2R; non degenerate primers amoA-2R-GG and amoA-2IR) were examined. No significant differences were observed among the three primers in terms of quantitative values of amoA from environmental samples using real-time PCR. We found that PCR-DGGE analysis with the amoA-2IR primer gave the best results in this studied soil. These results indicate that amoA-2IR is a suitable primer for community analysis of AOB in the environment. PMID- 22075623 TI - Analysis of early bacterial communities on volcanic deposits on the island of Miyake (Miyake-jima), Japan: a 6-year study at a fixed site. AB - Microbial colonization on new terrestrial substrates represents the initiation of new soil ecosystem formation. In this study, we analyzed early bacterial communities growing on volcanic ash deposits derived from the 2000 Mount Oyama eruption on the island of Miyake (Miyake-jima), Japan. A site was established in an unvegetated area near the summit and investigated over a 6-year period from 2003 to 2009. Collected samples were acidic (pH 3.0-3.6), did not utilize any organic substrates in ECO microplate assays (Biolog), and harbored around 106 cells (g dry weight)(-1) of autotrophic Fe(II) oxidizers by most-probable-number (MPN) counts. Acidithiobacillus ferrooxidans, Acidithiobacillus ferrivorans, and the Leptospirillum groups I, II and III were found to be abundant in the deposits by clone library analysis of bacterial 16S rRNA genes. The numerical dominance of Acidithiobacillus ferrooxidans was also supported by analysis of the gene coding for the large subunit of the form I ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO). Comparing the 16S rRNA gene clone libraries from samples differing in age, shifts in Fe(II)-oxidizing populations seemed to occur with deposit aging. The detection of known 16S rRNA gene sequences from Fe(III) reducing acidophiles promoted us to propose the acidity-driven iron cycle for the early microbial ecosystem on the deposit. PMID- 22075629 TI - Transapical access for thoracic endograft delivery. AB - The purpose of this paper is to describe the technique of transapical deployment of a thoracic endograft and to discuss the specifics of this access. The technique of endograft deployment through a transapical access is demonstrated in a patient with a symptomatic 14-cm aortic arch aneurysm. The 73-year-old patient, with concomitant chronic obstructive airway disease and cardiovascular disease, had been denied open surgery. Femoral artery access was deemed contraindicated because of a more distal concomitant type III thoracoabdominal aneurysm, borderline renal failure and heavily calcified iliac arteries. Bilateral iliac subclavian debranching and thoracic endografting via a combined transapical and left subclavian access successfully excluded the thoracic aortic aneurysm. The patient died within 24 hours postoperatively due to a massive myocardial infarction. In conclusion, transapical access for thoracic endograft delivery is feasible. Combined with complex debranching procedures in a challenging aneurysmal anatomy, it carries a high risk for periprocedural complications. PMID- 22075627 TI - CXCR4/CXCL12 expression profile is associated with tumor microenvironment and clinical outcome of liver metastases of colorectal cancer. AB - Interaction between CXCR4 and CXCL12 plays a role in tumor progression. The present study examined CXCR4, CXCL12 and CD133 expression in liver metastases of colorectal cancer (CLM) and determined whether the expression profiles affect the tumor microenvironment and thus progression, and whether they could serve as a prognostic marker for survival. Liver metastases of colorectal cancer collected from 92 patients were evaluated by CXCR4, CXCL12 and CD133 immunohistochemistry and clinicopathological data were analyzed. The expression profile of CXCR4 was determined in the colorectal cancer cell line, SW48. The expression of cytoplasmic CXCR4 was higher in 36 (39%) patients than that indicated by CXCR4 staining intensity of hepatocytes. High levels of nuclear CXCR4 expression in 23 (25%) patients significantly correlated with CXCL12 expression in hepatocytes. Nuclear CXCR4 expression was increased in the cancer cells after exposure to CXCL12. Univariate and multivariate analyses demonstrated that the high levels of nuclear CXCR4 and CXCL12 expression in hepatocytes were significantly better prognostic factors for overall and hepatic disease-free survival in patients with CLM. The expression of CXCR4 and CXCL12 in CLM may have an interactive effect that could alter the tumor microenvironment. CXCR4 expression in metastatic liver tumors together with the upregulation of CXCL12 in hepatocytes may help to predict the clinical outcomes of patients with CLM after hepatectomy. PMID- 22075630 TI - Development of production and purification processes of recombinant fragment of pneumococcal surface protein A in Escherichia coli using different carbon sources and chromatography sequences. AB - Pneumococcal surface protein A (PspA) is essential for Streptococcus pneumoniae virulence and its use either as a novel pneumococcal vaccine or as carrier in a conjugate vaccine would improve the protection and the coverage of the vaccine. Within this context, the development of scalable production and purification processes of His-tagged recombinant fragment of PspA from clade 3 (rfPspA3) in Escherichia coli BL21(DE3) was proposed. Fed-batch production was performed using chemically defined medium with glucose or glycerol as carbon source. Although the use of glycerol led to lower acetate production, the concentration of cells were similar at the end of both fed-batches, reaching high cell density of E. coli (62 g dry cell weight/L), and the rfPspA3 production was higher with glucose (3.48 g/L) than with glycerol (2.97 g/L). A study of downstream process was also carried out, including cell disruption and clarification steps. Normally, the first chromatography step for purification of His-tagged proteins is metal affinity. However, the purification design using anion exchange followed by metal affinity gave better results for rfPspA3 than the opposite sequence. Performing this new design of chromatography steps, rfPspA3 was obtained with 95.5% and 75.9% purity, respectively, from glucose and glycerol culture. Finally, after cation exchange chromatography, rfPspA3 purity reached 96.5% and 90.6%, respectively, from glucose and glycerol culture, and the protein was shown to have the expected alpha-helix secondary structure. PMID- 22075631 TI - Gas discharge plasmas are effective in inactivating Bacillus and Clostridium spores. AB - Bacterial spores are the most resistant form of life and have been a major threat to public health and food safety. Nonthermal atmospheric gas discharge plasma is a novel sterilization method that leaves no chemical residue. In our study, a helium radio-frequency cold plasma jet was used to examine its sporicidal effect on selected strains of Bacillus and Clostridium. The species tested included Bacillus subtilis, Bacillus stearothermophilus, Clostridium sporogenes, Clostridium perfringens, Clostridium difficile, and Clostridium botulinum type A and type E. The plasmas were effective in inactivating selected Bacillus and Clostridia spores with D values (decimal reduction time) ranging from 2 to 8 min. Among all spores tested, C. botulinum type A and C. sporogenes were significantly more resistant to plasma inactivation than other species. Observations by phase contrast microscopy showed that B. subtilis spores were severely damaged by plasmas and the majority of the treated spores were unable to initiate the germination process. There was no detectable fragmentation of the DNA when the spores were treated for up to 20 min. The release of dipicolinic acid was observed almost immediately after the plasma treatment, indicating the spore envelope damage could occur quickly resulting in dipicolinic acid release and the reduction of spore resistance. PMID- 22075632 TI - Luciferase and fluorescent protein as dual reporters analyzing the effect of n dodecyltrimethylammonium bromide on the physiology of Pseudomonas putida. AB - With the growing interest in using surfactants to improve microbial cell performance for whole-cell biocatalysis and bioremediation, understanding the interactions between surfactants and bacteria is of great importance. By using cyanine fluorescent protein (CFP) and bacterial luciferase (LUX) as dual bioreporters, the effects of n-dodecyltrimethylammonium bromide (DTAB) on the whole cells and intracellular proteins in Pseudomonas putida cultures were quantitatively and systematically studied. The dual reporter system was shown to be a useful indicator to assess the effect of DTAB treatment on whole-cell metabolic activity, membrane permeability, and cellular enzyme activity. CFP was useful to assess the leakage of intracellular enzymes and the lysis of cells and was able to reflect the activities of most cellular enzymes, while LUX reflected the permeability of cell membranes and cellular metabolic activity. The validity of CFP-LUX dual bioreporters was further confirmed by detecting changes in extracellular proteins, membrane potential, oxygen consumption rate (OUR), and intracellular catechol 2,3-dioxygenase (C23O) activity with the addition of DTAB. The dual LUX-CFP bioreporter is a useful tool for analyzing the surfactant bacterium interactions for biotechnological applications. PMID- 22075633 TI - Development of a glutathione production process from proteinaceous biomass resources using protease-displaying Saccharomyces cerevisiae. AB - Glutathione is a valuable tri-peptide that is widely used in the pharmaceutical, food, and cosmetic industries. Glutathione is produced industrially by fermentation using Saccharomyces cerevisiae, and supplementation of fermentation with several amino acids can increase intracellular GSH content. More recently, however, focus has been given to protein as a resource for biofuel and fine chemical production. We demonstrate that expression of a protease on the cell surface of S. cerevisiae enables the direct use of keratin and soy protein as a source of amino acids and that these substrates enhanced intracellular GSH content. Furthermore, fermentation using soy protein also enhanced cell concentration. GSH fermentation from keratin and to a greater extent from soy protein using protease-displaying yeast yielded greater GSH productivity compared to GSH fermentation with amino acid supplementation. This protease-displaying yeast is potentially applicable to a variety of processes for the bio-production of value-added chemicals from proteinaceous biomass resources. PMID- 22075634 TI - Biodegradation of Leonardite by an alkali-producing bacterial community and characterization of the degraded products. AB - In this study, three bacterial communities were obtained from 12 Leonardite samples with the aim of identifying a clean, effective, and economic technique for the dissolution of Leonardite, a type of low-grade coal, in the production of humic acid (HA). The biodegradation ability and characteristics of the degraded products of the most effective bacterial community (MCSL-2), which degraded 50% of the Leonardite within 21 days, were further investigated. Analyses of elemental composition, (13)C NMR, and Fourier transform infrared revealed that the contents of C, O, and aliphatic carbon were similar in biodegraded humic acid (bHA) and chemically (alkali) extracted humic acid (cHA). However, the N and carboxyl carbon contents of bHA was higher than that of cHA. Furthermore, a positive correlation was identified between the degradation efficiency and the increasing pH of the culture medium, while increases of manganese peroxidase and esterase activities were also observed. These data demonstrated that both alkali production and enzyme reactions were involved in Leonardite solubilization by MCSL-2, although the former mechanism predominated. No fungus was observed by microscopy. Only four bacterial phylotypes were recognized, and Bacillus licheniformis-related bacteria were identified as the main group in MCSL-2 by analysis of amplified 16S rRNA genes, thus demonstrating that Leonardite degradation ability has a limited distribution in bacteria. Hormone-like bioactivities of bHA were also detected. In this study, a bacterial community capable of Leonardite degradation was identified and the products characterized. These data implicate the use of such bacteria for the exploitation of Leonardite as a biofertilizer. PMID- 22075635 TI - Cloning, expression and characterization of a eukaryotic cycloalkanone monooxygenase from Cylindrocarpon radicicola ATCC 11011. AB - In this study, we have cloned and characterized a cycloalkanone monooxygenase (CAMO) from the ascomycete Cylindrocarpon radicicola ATCC 11011 (identical to Cylindrocarpon destructans DSM 837). The primary structure of this Baeyer Villiger monooxygenase (BMVO) revealed 531 residues with around 45% sequence identity to known cyclohexanone monooxygenases. The enzyme was functionally overexpressed in Escherichia coli and investigated with respect to substrate spectrum and kinetic parameters. Substrate specificity studies revealed that a large variety of cycloaliphatic and bicycloaliphatic ketones are converted by this CAMO. A high catalytic efficiency against cyclobutanone was observed and seems to be a particular property of this BVMO. The thus produced butyrolactone derivatives are valuable building blocks for the synthesis of a variety of natural products and bioactive compounds. Furthermore, the enzyme revealed activity against open-chain ketones such as cyclobutyl, cyclopentyl and cyclohexyl methyl ketone which have not been reported to be accepted by typical cyclohexanone monooxygenases. These results suggest that the BVMO from C. radicicola indeed might be rather unique and since no BVMOs originating from eukaryotic organisms have been produced recombinantly so far, this study provides the first example for such an enzyme. PMID- 22075636 TI - Extracellular production of cycloisomaltooligosaccharide glucanotransferase and cyclodextran by a protease-deficient Bacillus subtilis host-vector system. AB - A cycloisomaltooligosaccharide (CI; cyclodextran) production system was developed using a Bacillus subtilis expression system for the cycloisomaltooligosaccharide glucanotransferase (CITase) gene. The CITase gene of Bacillus circulans T-3040, along with the alpha-amylase promoter (PamyQ) and amyQ signal sequence of Bacillus amyloliquefaciens, was cloned into the Bacillus expression vector pUB110 and subsequently expressed in B. subtilis strain 168 and its alkaline (aprE) and neutral (nprE) protease-deficient strains. The recombinant CITase produced by the protease-deficient strains reached 1 U/mL in the culture supernatant within 48 h of cultivation, which was approximately 7.5 times more than that produced by the industrial CITase-producing strain B. circulans G22-10 derived from B. circulans T-3040. When aprE- and nprE-deficient B. subtilis 168 harboring the CITase gene was cultured with 10% dextran 40 for 48 h, 17% of the dextran in the culture was converted to CIs (CI-7 to CI-12), which was approximately three times more than that converted by B. circulans G22-10 under the same dextran concentration. The B. subtilis host-vector system enabled us to produce CIs by direct fermentation of dextran along with high CITase production, which was not possible in B. circulans G22-10 due to growth inhibition by dextran at high concentrations and limited production of CITase. PMID- 22075637 TI - PmST3 from Pasteurella multocida encoded by Pm1174 gene is a monofunctional alpha2-3-sialyltransferase. AB - Pasteurella multocida (Pm) strain Pm70 has three putative sialyltransferase genes including Pm0188, Pm0508, and Pm1174. A Pm0188 gene homolog in Pm strain P-1059 encodes a multifunctional alpha2-3-sialyltransferase, PmST1, that prefers oligosaccharide acceptors. A Pm0508 gene homolog in the same strain encodes a monofunctional sialyltransferase PmST2 that prefers glycolipid acceptors. Here, we report that the third sialyltransferase from Pm (PmST3) encoded by gene Pm1174 in strain Pm70 is a monofunctional alpha2-3-sialyltransferase that can use both oligosaccharides and glycolipids as efficient acceptors. Despite the existence of both Pm0188 and Pm0508 gene homologs encoding PmST1 and PmST2, respectively, in Pm strain P-1059, a Pm1174 gene homolog appears to be absent from Pm strains P 1059 and P-934. PmST3 was successfully obtained by cloning and expression using a synthetic gene of Pm1174 with codons optimized for Escherichia coli expression system as the DNA template for polymer chain reactions. Truncation of 35 amino acid residues from the carboxyl terminus was shown to improve the expression of a soluble and active enzyme in E. coli as a C-His(6)-tagged fusion protein. This sialidase-free monofunctional alpha2-3-sialyltransferase is a useful tool for synthesizing sialylated oligosaccharides and glycolipids. PMID- 22075638 TI - Swim training does not protect mice from skeletal muscle oxidative damage following a maximum exercise test. AB - We investigated whether swim training protects skeletal muscle from oxidative damage in response to a maximum progressive exercise. First, we investigated the effect of swim training on the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the gastrocnemius muscle of C57Bl/6 mice, 48 h after the last training session. Mice swam for 90 min, twice a day, for 5 weeks at 31 degrees C (+/- 1 degrees C). The activities of SOD and CAT were increased in trained mice (P < 0.05) compared to untrained group. However, no effect of training was observed in the activity of GPx. In a second experiment, trained and untrained mice were submitted to a maximum progressive swim test. Compared to control mice (untrained, not acutely exercised), malondialdehyde (MDA) levels were increased in the skeletal muscle of both trained and untrained mice after maximum swim. The activity of GPx was increased in the skeletal muscle of both trained and untrained mice, while SOD activity was increased only in trained mice after maximum swimming. CAT activity was increased only in the untrained compared to the control group. Although the trained mice showed increased activity of citrate synthase in skeletal muscle, swim performance was not different compared to untrained mice. Our results show an imbalance in the activities of SOD, CAT and GPx in response to swim training, which could account for the oxidative damage observed in the skeletal muscle of trained mice in response to maximum swim, resulting in the absence of improved exercise performance. PMID- 22075639 TI - Allometric scaling of 6-min walking distance by body mass as a standardized measure of exercise capacity in healthy adults. AB - Body mass (BM) is a confounding variable in human performance. We hypothesized that adjusting 6-min walk distance (6MWD) for BM differences using allometric scaling would allow meaningful individual and group comparisons. We aimed to use allometric scaling of 6MWD to BM to provide an index for comparing walking performance in middle-aged and older adults. One hundred and twenty subjects (40 87 years) participated. Anthropometry, spirometry, and two walk tests were evaluated. We adjusted 6MWD to BM, gender, and age using an allometric procedure. The allometric exponents were prospectively applied in a validation sample of 44 healthy subjects. Body mass presented significant negative correlation (p < 0.01) with 6MWD . BM(-1) in middle-aged and older adults (r = -0.70 and -0.46, respectively). The allometric exponent (b) for 6MWD was significantly higher for older than middle-aged adults (0.35 +/- 0.20 vs. 0.11 +/- 0.08, respectively). The resulting BM exponents were similar in male and female subjects (0.22 +/- 0.13 and 0.17 +/- 0.09, respectively). The correlation between 6MWD . BM(-b ) and BM using the exponents (0.11 or 0.35) was not statistically different from zero (r = 0.00) in the validation sample, suggesting that allometric analysis did not penalize the subjects based on BM. Allometric scaling of 6MWD in middle-aged and older adults may be useful for evaluating walking performance free of the confounding effect of BM, even in the absence of a table of norms. PMID- 22075640 TI - Metabolic and functional effects of beta-hydroxy-beta-methylbutyrate (HMB) supplementation in skeletal muscle. AB - Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite derived from leucine. The anti-catabolic effect of HMB is well documented but its effect upon skeletal muscle strength and fatigue is still uncertain. In the present study, male Wistar rats were supplemented with HMB (320 mg/kg per day) for 4 weeks. Placebo group received saline solution only. Muscle strength (twitch and tetanic force) and resistance to acute muscle fatigue of the gastrocnemius muscle were evaluated by direct electrical stimulation of the sciatic nerve. The content of ATP and glycogen in red and white portions of gastrocnemius muscle were also evaluated. The effect of HMB on citrate synthase (CS) activity was also investigated. Muscle tetanic force was increased by HMB supplementation. No change was observed in time to peak of contraction and relaxation time. Resistance to acute muscle fatigue during intense contractile activity was also improved after HMB supplementation. Glycogen content was increased in both white (by fivefold) and red (by fourfold) portions of gastrocnemius muscle. HMB supplementation also increased the ATP content in red (by twofold) and white (1.2-fold) portions of gastrocnemius muscle. CS activity was increased by twofold in red portion of gastrocnemius muscle. These results support the proposition that HMB supplementation have marked change in oxidative metabolism improving muscle strength generation and performance during intense contractions. PMID- 22075641 TI - Experimental knee pain impairs postural stability during quiet stance but not after perturbations. AB - The objective of this study was to examine the effect of experimental knee related pain on postural control. Twelve healthy subjects stood as quietly as possible on a movable force platform (that measured the centre of pressure and provided fast perturbations) before, during, and after experimental knee-related pain. Lower limb electromyographic (EMG) activity and joint angles were measured. Experimental pain was induced by injecting hypertonic saline into the infrapatellar fat pad (unilateral and bilateral) and isotonic saline was used for control sessions. Compared with the baseline and control sessions, unilateral and bilateral knee-related pain during quiet standing evoked (1) an increased sway displacement in the anterior-posterior direction (P < 0.05), (2) larger knee flexion (P < 0.05), and (3) larger EMG changes. Bilateral pain also induced (1) larger medial-lateral sway displacement and speed (P < 0.05) and (2) larger left hip flexion (P < 0.05). During forward perturbations, subjects leaned forward during both painful conditions when compared with baseline (P < 0.05). The additional impairment by bilateral pain suggests that the non-painful limb in unilateral pain conditions compensates for the impaired postural control. These results show that knee-related pain impairs postural stability during quiet standing, indicating the vulnerability of patients with knee pain to falls. This measure could potentially help clinicians who seek to assess how pain responses may contribute to patient's postural control and stability during quiet standing. PMID- 22075642 TI - Is glucose-6-phosphate dehydrogenase deficiency a risk factor for hyperbaric oxygen exposure? AB - Divers and patients lacking glucose-6-phosphate dehydrogenase (G6PD) may face a serious threat of central nervous system oxygen toxicity (CNS-OT) during exposure to hyperbaric oxygen (HBO), due to the important part played by G6PD in cellular redox balance. Our objective was to investigate G6PD deficiency as a risk factor for CNS-OT. We exposed G6PD-deficient (G6PDdef) and wild type (WT) mice to HBO at 405 kPa. Latency to CNS-OT was measured by observing the animal and monitoring the time to appearance of convulsions. Changes in glutathione peroxidase (GPx) and catalase activity were measured in red blood cells, and levels of endothelial and neuronal nitric oxide synthase (eNOS and nNOS) and 3-nitrotyrosine (NT) were measured in extracts of whole brain tissue by Western blot analysis. Unexpectedly, latency to CNS-OT was more than twice as long in G6PDdef mice compared with WT (36.9 +/- 15.4 and 15.6 +/- 13.2 min, respectively, P < 0.005). No significant differences were found in GPx and catalase activity or in protein levels of eNOS. However, nNOS and NT levels were lower in G6PDdef mice compared with WT (50.6%, P < 0.01 and 52.8%, P < 0.05, respectively). Our results suggest that the enhanced resistance of G6PDdef mice to HBO is due in part to a reduction in nNOS and NT levels in the brain. We conclude that G6PD deficiency at the level of the animals in the present study may not be a risk factor for developing CSN OT, but this remains to be verified for human subjects. PMID- 22075643 TI - Validity, reliability and stability of the portable Cortex Metamax 3B gas analysis system. AB - This study investigated the performance of the portable Cortex Metamax 3B (MM3B) automated gas analysis system during both simulated and human exercise using adolescents. Repeated measures using a Gas Exchange System Validator (GESV) across a range of simulated metabolic rates, showed the MM3B to be adequately reliable (both percentage errors, and percentage technical error of measurements <2%) for measuring expired ventilation (V (E)), oxygen consumption (VO(2)), and carbon dioxide production (VCO(2)). Over a 3 h period, the MM3B was shown to be acceptably stable in measuring gas fractions, as well as V (E), VO(2), and VCO(2) generated by the GESV, especially at moderate and high metabolic rates (drifts <2% and of minor physiological significance). Using eight healthy adolescents during rest, moderate, and vigorous cycle ergometry, the validity of the MM3B was tested against the primary criterion Douglas bag method (DBM) and a secondary criterion machine known to be accurate, the Jaeger Oxycon Pro system. No significant errors in V (E) were noted, yet the MM3B significantly overestimated both VO(2) and VCO(2) by approximately 10-17% at moderate and vigorous exercise as compared to the DBM and at all exercise levels compared to the Oxycon Pro. No significant differences were seen in any metabolic variable between the two criterion systems (DBM and Oxycon Pro). It is concluded the MM3B produces acceptably stable and reliable results, but is not adequately valid during moderate and vigorous exercise without some further correction of VO(2) and VCO(2). PMID- 22075644 TI - Does exercise duration affect Fatmax in overweight boys? AB - To compare the assessment of Fat(max) using a single graded exercise test with 3 min stages against 30 min prolonged exercise bouts in overweight boys. Ten overweight boys (8-12 years) attended the laboratory on seven separate occasions. On the first visit, body anthropometrics and peak aerobic capacity ([Formula: see text]O(2peak)) were assessed. Following this, each participant attended the laboratory after an overnight fast for six morning cycling sessions. During the first session, participants completed a continuous, submaximal graded exercise protocol with seven 3 min stages (GRAD) at 35, 40, 45, 50, 55, 60 and 65% [Formula: see text]O(2peak). The final five visits consisted of a 30 min bout of prolonged exercise (PROL) performed in a counterbalanced order at 40, 45, 50, 55 and 60% [Formula: see text]O(2peak). There was no effect of exercise duration on Fat(max) or the absolute rate of fat oxidation during PROL (p > 0.05). At the group level, GRAD and PROL provided similar estimates of Fat(max) (GRAD: 53 +/- 10% [Formula: see text]O(2peak); PROL: 53 +/- 10% [Formula: see text]O(2peak); p = 0.995); however, individual variation between the two protocols is shown by a systematic bias and residual error of 0 +/- 11% [Formula: see text]O(2peak). Fat oxidation rates remained stable across 30 min of steady-state exercise in overweight boys. Furthermore, Fat(max) was similar at 3, 10, 20 and 30 min of exercise, suggesting that for exercise lasting <= 30 min, exercise duration does not affect Fat(max). However, Fat(max) determined with GRAD may need to be interpreted with caution at the individual level given the variation in Fat(max) between protocols. PMID- 22075645 TI - The plant hormone abscisic acid increases in human plasma after hyperglycemia and stimulates glucose consumption by adipocytes and myoblasts. AB - The plant hormone abscisic acid (ABA) is released from glucose-challenged human pancreatic beta cells and stimulates insulin secretion. We investigated whether plasma ABA increased during oral and intravenous glucose tolerance tests (OGTTs and IVGTTs) in healthy human subjects. In all subjects undergoing OGTTs (n=8), plasma ABA increased over basal values (in a range from 2- to 9-fold). A positive correlation was found between the ABA area under the curve (AUC) and the glucose AUC. In 4 out of 6 IVGTTs, little or no increase of ABA levels was observed. In the remaining subjects, the ABA increase was similar to that recorded during OGTTs. GLP-1 stimulated ABA release from an insulinoma cell line and from human islets, by ~10- and 2-fold in low and high glucose, respectively. Human adipose tissue also released ABA in response to high glucose. Nanomolar ABA stimulated glucose uptake, similarly to insulin, in rat L6 myoblasts and in murine 3T3-L1 cells differentiated to adipocytes, by increasing GLUT-4 translocation to the plasma membrane. Demonstration that a glucose load in humans is followed by a physiological rise of plasma ABA, which can enhance glucose uptake by adipose tissues and muscle cells, identifies ABA as a new mammalian hormone involved in glucose metabolism. PMID- 22075648 TI - Methylphenidate treatment of adult male prison inmates with attention-deficit hyperactivity disorder: randomised double-blind placebo-controlled trial with open-label extension. AB - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is highly prevalent in prison inmates, but pharmacological treatment has not yet been evaluated in this group. AIMS: To evaluate osmotic-release oral system (OROS) methylphenidate in adult male long-term prison inmates with ADHD. METHOD: Randomised, double blind, placebo-controlled 5-week trial, followed by 47-week open-label extension in 30 prison inmates with ADHD and comorbid disorders. Primary outcome was level of ADHD symptoms after 5 weeks, evaluated by a masked assessor. Secondary outcomes were self-reported ADHD symptoms, global severity and global functioning throughout the 52-week trial, and post hoc treatment response and numbers needed to treat (NNT) (trial registration: NCT00482313.) RESULTS: Treatment significantly improved ADHD during the trial (P<0.001; Cohen's d = 2.17), with reduced symptom severity and improved global functioning. The placebo response, cardiovascular measures and adverse events were non-significant; the NNT was 1.1. Attention-deficit hyperactivity disorder symptoms, global severity and global functioning continued to improve during the open-label extension. CONCLUSIONS: Osmotic-release oral system methylphenidate is an effective treatment for adult male prison inmates with ADHD. PMID- 22075646 TI - Opposing roles of RAGE and Myd88 signaling in extensive liver resection. AB - In extensive liver resection secondary to primary or metastatic liver tumors, or in living donor liver transplantation, strategies to quell deleterious inflammatory responses and facilitate regeneration are essential. The receptor for advanced glycation endproducts (RAGE) and myeloid differentiating factor 88 (Myd88) are implicated in the inflammatory response. To establish the contributions of RAGE vs. Myd88 signaling in extensive liver resection, we probed the effect of RAGE and/or Myd88, the latter primarily a key transducer of major toll-like receptors and also implicated in interleukin-1 (Il1) signaling, in a murine model of extensive (85%) hepatectomy. We report that, although Myd88 is thoroughly essential for survival via regulation of NF-kappaB and TNF-alpha, deletion of RAGE significantly improved survival compared to wild-type, Myd88 null, or RAGE-null/Myd88-null mice. RAGE opposes Myd88 signaling at multiple levels: by suppression of p65 levels, thereby reducing activation of NF-kappaB and consequent production of cyclin D1, and by suppression of Il6-mediated phosphorylation of Stat3, thereby down-regulating Pim1 and suppressing the hyperplastic response. Further, RAGE-dependent suppression of glyoxalase1, a detoxification pathway for pre-AGEs, enhances AGE levels and suppresses Il6 action. We conclude that blockade of RAGE may rescue liver remnants from the multiple signals that preclude adaptive proliferation triggered primarily by Myd88 signaling pathways. PMID- 22075647 TI - Soluble miniagrin enhances contractile function of engineered skeletal muscle. AB - Neural agrin plays a pleiotropic role in skeletal muscle innervation and maturation, but its specific effects on the contractile function of aneural engineered muscle remain unknown. In this study, neonatal rat skeletal myoblasts cultured within 3-dimensional engineered muscle tissue constructs were treated with 10 nM soluble recombinant miniagrin and assessed using histological, biochemical, and functional assays. Depending on the treatment duration and onset time relative to the stage of myogenic differentiation, miniagrin was found to induce up to 1.7-fold increase in twitch and tetanus force amplitude. This effect was associated with the 2.3-fold up-regulation of dystrophin gene expression at 6 d after agrin removal and enhanced ACh receptor (AChR) cluster formation, but no change in cell number, expression of muscle myosin, or important aspects of intracellular Ca(2+) handling. In muscle constructs with endogenous ACh levels suppressed by the application of alpha-NETA, miniagrin increased AChR clustering and twitch force amplitude but failed to improve intracellular Ca(2+) handling and increase tetanus-to-twitch ratio. Overall, our studies suggest that besides its synaptogenic function that could promote integration of engineered muscle constructs in vivo, neural agrin can directly promote the contractile function of aneural engineered muscle via mechanisms distinct from those involving endogenous ACh. PMID- 22075649 TI - Preventing progression to first-episode psychosis in early initial prodromal states. AB - BACKGROUND: Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred. AIMS: To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS. METHOD: A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up. RESULTS: A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow up (6.3% v. 20.0%; P = 0.019). CONCLUSIONS: Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS. PMID- 22075650 TI - Features of subsyndromal and persistent delirium. AB - BACKGROUND: Longitudinal studies of delirium phenomenology are lacking. AIMS: We studied features that characterise subsyndromal delirium and persistent delirium over time. METHOD: Twice-weekly evaluations of 100 adults with DSM-IV delirium using the Delirium Rating Scale-Revised-98 (DRS-R98) and Cognitive Test for Delirium (CTD). The generalised estimating equation method identified symptom patterns distinguishing full syndromal from subsyndromal delirium and resolving from persistent delirium. RESULTS: Participants (mean age 70.2 years (s.d. = 10.5)) underwent 323 assessments (range 2-9). Full syndromal delirium was significantly more severe than subsyndromal delirium for DRS-R98 thought process abnormalities, delusions, hallucinations, agitation, retardation, orientation, attention, and short- and long-term memory items, and CTD attention, vigilance, orientation and memory. Persistent full syndromal delirium had greater disturbance of DRS-R98 thought process abnormalities, delusions, agitation, orientation, attention, and short- and long-term memory items, and CTD attention, vigilance and orientation. CONCLUSIONS: Full syndromal delirium differs from subsyndromal delirium over time by greater severity of many cognitive and non cognitive symptoms. Persistent delirium involves increasing prominence of recognised core diagnostic features and cognitive impairment. PMID- 22075651 TI - Brief psychodynamic interpersonal psychotherapy for patients with multisomatoform disorder: randomised controlled trial. AB - BACKGROUND: Multisomatoform disorder is characterised by severe and disabling bodily symptoms, and pain is one of the most common and impairing of these. Furthermore, these bodily symptoms cannot be explained by an underlying organic disorder. Patients with multisomatoform disorder are commonly found at all levels of healthcare and are typically difficult to treat for physicians as well as for mental health specialists. AIMS: To test whether brief psychodynamic interpersonal therapy (PIT) effectively improves the physical quality of life in patients who have had multisomatoform disorder for at least 2 years. METHOD: We recruited 211 patients (from six German academic outpatient centres) who met the criteria for multisomatoform disorder for a randomised, controlled, 12-week, parallelgroup trial from 1 July 2006 to 1 January 2009 (International Standard Randomised Controlled Trial Number ISRCTN23215121). We randomly assigned the patients to receive either 12 weekly sessions of PIT (n = 107) or three sessions of enhanced medical care (EMC, n = 104). The physical component summary of the Short Form Health Survey (SF-36) was the pre-specified primary outcome at a 9 month follow-up. RESULTS: Psychodynamic interpersonal therapy improved patients' physical quality of life at follow-up better than EMC (mean improvement in SF-36 score: PIT 5.3, EMC 2.2), with a small to medium between-group effect size (d = 0.42, 95% CI 0.15-0.69, P = 0.001). We also observed a significant improvement in somatisation but not in depression, health anxiety or healthcare utilisation. CONCLUSIONS: This trial documents the long-term efficacy of brief PIT for improving the physical quality of life in patients with multiple, difficult-to treat, medically unexplained symptoms. PMID- 22075652 TI - A Diels-Alder approach to the enantioselective construction of fluoromethylated stereogenic carbon centers. AB - Highly enantioselective Diels-Alder reactions of beta-fluoromethylacrylates were carried out in the presence of a Lewis acid activated chiral oxazaborolidine catalyst. These reactions yielded fluoromethylated cyclohexenes, including trifluoromethyl-, difluoromethyl-, and monofluoromethyl cyclohexenes, as nearly pure enantiomers. The resulting fluoromethyl cyclohexenes were converted into potential synthetic intermediates for bioactive compounds. PMID- 22075653 TI - Identification of clinical and laboratory markers for predicting eosinophilic esophagitis in adults. AB - BACKGROUND: The diagnosis of eosinophilic esophagitis (EoE) and differentiation from gastroesophageal reflux disease (GERD) is potentially challenging and is based upon clinical signs and endoscopic and histological features. In order to alert the endoscopist to consider EoE in patients with esophageal symptoms before performing esophagogastroduodenoscopy, we aimed to identify a set of clinical and laboratory markers for predicting EoE. METHODS: The study included 43 patients with either EoE (n = 23) or GERD (n = 20). The diagnosis of EoE was based on International Consensus Criteria. Age, gender, weight loss, history of atopy, dysphagia, history of food impaction, proton pump inhibitor (PPI) refractory heartburn, odynophagia, peripheral eosinophilia, and serum IgE were analyzed. Each symptom or sign was classified as '0' (absent, normal) or '1' (present, elevated), individually analyzed and statistically evaluated among the two groups of patients. Logistic regression analysis was carried out to identify a clinically applicable marker constellation to differentiate EoE from GERD. RESULTS: Univariate analysis identified 6 out of the 10 variables to be significant between both groups. A stepwise procedure of logistic regression led to a model in which 3 out of the initial 10 items were found to be relevant for differentiating GERD and EoE. Derived from this model, an optimal differentiation was achieved by using the following simplified equation: peripheral eosinophilia + history of food impaction + PPI refractory heartburn leading to a maximal value of 3 (1 + 1 + 1). Based on a cut-off value of >=2, sensitivity and specificity for diagnosing EoE were 91 and 100%, respectively. CONCLUSION: A defined set of markers including two clinical features and one laboratory parameter is highly predictive of EoE and thus allows physicians to distinguish EoE from GERD even before upper gastrointestinal endoscopy is performed. PMID- 22075654 TI - Insight into the structural characteristics of core-links and flat-aluminum tridecamers: a density functional theory study. AB - The structures of core-links Al(13) (C-Al(13)) and flat-Al(13) (F-Al(13)) complexes in aqueous solution have been investigated using density functional theory (DFT) at the level of B3LYP/6-31G(d). The present work focuses on the following three aspects: (1) C-Al(13)(9+) was optimized with the consideration of solvent effect and the (27)Al NMR chemical shifts using Hartree Fock GIAO and B3LYP GIAO methods were computed respectively; (2) the optimization of F Al(13)(15+) was also performed and the (27)Al NMR chemical shifts were obtained using the same methods as above; (3) the structural parameters of a series of typical aluminum species (Al(3+), AlOH(2+), AlF(2+), Al(2)(4+), Al(6)(6+), K Al(13)(7+), C-Al(13)(9+) and F-Al(13)(15+)) were compared. PMID- 22075656 TI - Stenting of a gastroduodenal artery aneurysm: report of a case. AB - We present a case of gastroduodenal artery stenting in a patient with recurrent episodes of pancreatitis due to gastroduodenal artery aneurysm. Stenting was performed under local anesthesia using a 6 * 38-mm primary covered Advanta V12 vascular stent graft. The procedure was successful and the patient is asymptomatic 21 months later. Endovascular treatment of gastroduodenal artery aneurysm should be considered a promising alternative to open surgery, due to lower mortality and morbidity. PMID- 22075655 TI - Chylothorax after neck dissection for thyroid carcinomas: report of three cases. AB - Chylothorax is a rare complication of neck dissection. We report three cases of chylothorax after neck dissections for thyroid carcinoma and attribute this relatively high incidence to the assumption that most patients are asymptomatic. Thus, conventional chest X-ray or ultrasonography in the early postoperative period may be warranted to exclude asymptomatic chylothorax, especially if the thoracic duct is injured and ligated during the operation. We suggest that for chylothorax induced by ligation of the thoracic duct, which may be transient and resolve quickly, short-term thoracic drainage is enough. PMID- 22075657 TI - Innovative segmentectomy to remove the posterior segment of the lower lobe (S10) of the lung. AB - We describe our innovative technique for performing segmentectomy of the posterior segment of the lower lobe of the lung, being segment number 10 (S10). In segmentectomy of S10, it is difficult to identify A10 from the interlobar fissure because the pulmonary artery to S10 (A10) branches from A(9+10) and runs dorsally and deeply into the lung tissue. Moreover, to reach S10 from the interlobar fissure, the lung tissue should be cut between S6 and S8, because S10 is not located beside the interlobar fissure. However, it is difficult to identify the boundary between the S6 and S8 without a route marker. To solve these difficulties, we divided S6 and S10 from each other at the beginning of the procedure, which enabled A10 to be identified easily from the dorsal side. Because S6 and S(8-10) should be divided in S10 segmentectomy at the end, the division between S6 and S(8-10) at the beginning of procedure is not only reasonable, but makes the procedure simple. PMID- 22075658 TI - Choriocarcinoma of the sigmoid colon: report of a case. AB - We report a rare case of primary choriocarcinoma of the colon. A 58-year-old woman underwent Hartmann's procedure to remove a sigmoid colon tumor, and pathological examination confirmed choriocarcinoma that had originated from the colon. Radical surgery combined with chemotherapy gives the best chance of long term survival. PMID- 22075659 TI - Video-assisted surgery for gastric carcinoma arising in a gastric tube reconstructed retrosternally. AB - Advances in diagnostic and surgical techniques have improved the prognosis of esophageal cancer, but there is growing concern about gastric tube cancer after esophagectomy. Gastric carcinoma arising in tubes that were reconstructed retrosternally is usually resected through a median sternotomy; however, this is invasive and carries a risk of osteomyelitis after suture-line failure. We performed video-assisted gastric tube resection, eliminating the need for sternotomy by using a sternal lifting method, on a 71-year-old man who had previously undergone esophagectomy and reconstruction retrosternally. The tumor was a Borrmann type 1 advanced cancer located near the esophagogastric anastomosis. Neck collar and upper abdominal incisions were made, and the sternum was lifted using a Kent retractor to extend the retrosternal space. Under videoscope assistance, we stripped the adhesions around the gastric tube carefully and performed total gastric tube resection. For the reconstruction, the ileocolon was lifted through the retrosternal space, and an ileoesophagostomy and Roux-en-Y reconstruction were performed. Despite leakage from an esophago ileoanastomosis on postoperative day 6, the patient recovered well without mediastinitis or osteomyelitis of the sternum. Thus, our surgical procedure provides a good surgical view, decreases surgical stress, and reduces the risk of fatal postoperative complications. PMID- 22075660 TI - Totally laparoscopic colectomy with intracorporeal anastomosis achieved using a laparoscopic linear stapler: experience of a single institute. AB - PURPOSE: Laparoscopic colonic surgery is now widely accepted. We assessed the safety and effectiveness of using a total intracorporeal surgical strategy to perform intracorporeal functional end-to-end anastomosis with an endoscopic linear stapler to treat colon cancer. METHODS: Forty-three selected patients underwent elective laparoscopic colon resection for carcinoma. A total intracorporeal colon resection was performed in all patients, using a functional end-to-end anastomosis with an endoscopic linear stapler. RESULTS: Good results were achieved in all 43 patients, none of whom required conversion to open surgery with extracorporeal anastomosis. There have been no intraoperative complications related to this technique and no instances of postoperative anastomotic leakage, intra-abdominal abscess, or wound infection. CONCLUSION: Intracorporeal functional end-to-end anastomosis using a linear stapler can be performed safely and easily for the resection of any part of the colon. We consider it an effective modality for totally laparoscopic colon resection. Favorable results have been achieved by this method, particularly for small tumors, since natural-orifice transluminal endoscopic surgery remains a challenging method to perform. PMID- 22075661 TI - Adult transmesenteric hernia: report of two cases. AB - Transmesenteric hernia is a rare cause of bowel obstruction in adults. We herein describe two cases that occurred in adult women, ages 27 and 19. Both cases presented with abdominal pain without muscular defense signs. Computed tomography of both cases showed features of small bowel obstruction by an internal hernia. A laparotomy showed mesenteric defects of the mesentery of the ileum in the former case and the mesentery of the transverse colon in the latter case, with a herniating ileum. The involved small bowel was viable in both cases, and the bowel was pulled out of the mesenteric defect without resection. The mesenteric defects were then successfully repaired. PMID- 22075662 TI - Pancreatic injury after major hepatectomy: a study in a porcine model. AB - PURPOSE: The aim of this study was to investigate the pathophysiology of pancreatitis after major hepatectomy. METHODS: The study used ten female pigs. Three served as sham animals (sham group) and were killed after laparotomy to obtain normal tissue samples. Seven animals were subjected to major hepatectomy (70-75%), using the Pringle maneuver for 150 min, after constructing a portacaval side-to-side anastomosis (hepatectomy group). Duration of reperfusion was 24 h. RESULTS: Pancreatic tissue sampled 24 h after reperfusion had increased necrosis and edema in comparison to sham group and to tissue sampled at 12 h. Tissue malondialdehyde (MDA) did not differ significantly between samples at 12 and 24 h but was increased in the hepatectomy group in comparison to sham animals. Percentage increase in portal MDA content during reperfusion was greater at 12 h of reperfusion in comparison to the increase after 24 h. Portal pressure increased significantly after 12 h of reperfusion. Serum amylase and C-peptide increased during reperfusion in comparison to baseline levels. CONCLUSIONS: The findings suggest that intraoperative portal congestion is not the only cause of the development of pancreatitis after major hepatectomy. The oxidative markers suggest that reactive oxygen species produced during vascular control may be responsible as well. PMID- 22075663 TI - Total mesorectal excision of initially unresectable locally advanced rectal cancer infiltrating the pelvic wall after treatment with FOLFOX4 plus bevacizumab and preoperative chemoradiation: report of a case. AB - A 60-year-old man underwent sigmoid loop colostomy for obstructive rectal cancer. Computed tomography (CT) showed a circumferential thickening of the lower rectal wall caused by a tumor invading the posterior and side pelvic wall. As we considered R0 resection too difficult, we gave the patient bevacizumab plus FOLFOX4 (oxaliplatin, leucovorin, and 5-fluorouracil). After eight courses, CT showed improvement in the rectal wall thickening but linear thickening of the mesorectal fascia remained. We therefore gave the patient chemoradiotherapy (CRT), and then 10 weeks later performed Hartmann's operation laparoscopically. Microscopic examination revealed that the tumor had been almost replaced by fibrous tissue, with only a few cancer cells left in the subserosa. The circumferential resection margin was free of cancer cells. The patient is doing well after 27 months of follow-up. This case suggests that systemic chemotherapy with FOLFOX4 plus bevacizumab prior to conventional preoperative CRT is a promising strategy for patients with initially unresectable locally advanced rectal cancer. PMID- 22075664 TI - Reevaluation of serum p53 antibody as a tumor marker in colorectal cancer patients. AB - PURPOSE: We reevaluated the serum p53 antibody (S-p53Ab) ELISA kit, which was approved as a tumor marker of colon cancer in the Japanese Health Insurance System in 2007. METHODS: S-p53Ab was measured as a tumor marker in 154 colorectal cancer patients, and the results were categorized by clinical and pathological variables. We then compared the positive frequency of S-p53Ab, carcinoembryonic antigen (CEA), and carbohydrate 19-9 (CA19-9). RESULTS: S-p53Ab was positive in 33.1% of the colorectal cancer patients. The positive rate was significantly higher in patients with lymph nodes metastasis (P = 0.025) and lymphatic invasion (P = 0.023). In patients with stage I colorectal cancer, the positive rate of S p53Ab (23.7%) was significantly higher than that of CEA (5.3%) or CA19-9 (7.9%). CONCLUSION: The approved kit for S-p53Ab testing was found to be an effective tumor marker of colorectal cancer. The positive rate of S-p53Ab was significantly higher in patients with cancer involvement of the lymphoid tissues. The positive rate of S-p53Ab was higher than that of CEA and CA19-9 in patients with stage I colorectal cancer, suggesting that the S-p53Ab is a useful tumor marker for patients with early-stage disease. PMID- 22075665 TI - Ultrasound-guided microwave coagulation assists anatomical hepatic resection. AB - PURPOSE: We describe a new technique of ultrasound (US)-guided microwave coagulation (MC) of the Glissonean pedicle, performed before transection to control the inflow and select the resection area. This report introduces our procedure and evaluates the outcomes of patients treated using this technique. METHODS: The Glissonean pedicles feeding the segment or cone unit were coagulated by US-guided MC, after which transection was performed. We used this US-guided MC technique to perform anatomical resections in 12 patients with hepatocellular carcinoma (MC group). We compared the outcomes of this group with those of a historical group of 10 patients who underwent conventional hepatectomy (control group). The two groups were well matched for age, tumor size, location, and type of hepatectomy. RESULTS: The mean operative times were similar, but the mean blood loss was significantly lower the in MC group than in the control group. Recurrence developed in four patients from the MC group, but local recurrence was not observed. Bile leakage occurred in one patient from the MC group, but the incidences of postoperative complications did not differ between the groups. CONCLUSIONS: Our procedure allows anatomical resection to be performed safely and easily, and helps prevent intrahepatic metastasis via portal flow during the transection. PMID- 22075666 TI - Preoperative evaluation of the depth of anal canal invasion in very low rectal cancer by magnetic resonance imaging and surgical indications for intersphincteric resection. AB - PURPOSE: The present study was performed to evaluate the depth of anal canal invasion (DACI), and determine whether magnetic resonance imaging (MRI) assessment of the conjoined longitudinal muscle (CLM) can be used to identify the surgical indication for intersphincteric resection. METHODS: Sixty-six patients with T1 (n = 2), T2 (n = 20), T3 (n = 39), and T4 (n = 5) lower rectal cancer were included. Depth of anal canal invasion was defined as extension of the tumor to the anal canal. The outline of the CLM on MRI was assessed as clear, unclear, or absent (indicating invasion). RESULTS: A comparison of overall T-stage and DACI of 22 pT1-pT2 tumors revealed that none had a higher T-stage within the anal canal, and 16 of 39 pT3 tumors had only pT0-pT2 invasion within the anal canal. The CLM was clear in 30 cases of T0-T2 DACI, unclear in 5 cases of T0-T2 DACI, and 3 cases of T3-T4 DACI, and showed invasion in 3 cases of T2 DACI and 25 cases of T3-T4 DACI. The sensitivity, specificity, positive predictive value, and negative predictive value of using a clear CLM outline for determining T0-T2 DACI was 78.9, 91.9, 100, and 77.8%, respectively. CONCLUSIONS: Preoperative evaluation of DACI was compatible with the surgical indications. A clear CLM accurately indicates T0-T2 DACI. PMID- 22075667 TI - Molecular, kinetic and thermodynamic characterization of Mycobacterium tuberculosis orotate phosphoribosyltransferase. AB - Tuberculosis (TB) is a chronic infectious disease caused mainly by Mycobacterium tuberculosis. The worldwide emergence of drug-resistant strains, the increasing number of infected patients among immune compromised populations, and the large number of latent infected individuals that are reservoir to the disease have underscored the urgent need of new strategies to treat TB. The nucleotide metabolism pathways provide promising molecular targets for the development of novel drugs against active TB and may, hopefully, also be effective against latent forms of the pathogen. The orotate phosphoribosyltransferase (OPRT) enzyme of the de novo pyrimidine synthesis pathway catalyzes the reversible phosphoribosyl transfer from 5'-phospho-alpha-D-ribose 1'-diphosphate (PRPP) to orotic acid (OA), forming pyrophosphate and orotidine 5'-monophosphate (OMP). Here we describe cloning and characterization of pyrE-encoded protein of M. tuberculosis H37Rv strain as a homodimeric functional OPRT enzyme. The M. tuberculosis OPRT true kinetic constants for forward reaction and product inhibition results suggest a Mono-Iso Ordered Bi-Bi kinetic mechanism, which has not been previously described for this enzyme family. Absence of detection of half reaction and isothermal titration calorimetry (ITC) data support the proposed mechanism. ITC data also provided thermodynamic signatures of non covalent interactions between substrate/product and M. tuberculosis OPRT. These data provide a solid foundation on which to base target-based rational design of anti-TB agents and should inform us how to better design inhibitors of M. tuberculosis OPRT. PMID- 22075668 TI - Sitagliptin and simvastatin (juvisync). PMID- 22075669 TI - Tadalafil (Cialis) for signs and symptoms of benign prostatic hyperplasia. PMID- 22075670 TI - Vassopressors and inotropes. PMID- 22075671 TI - A-kinase anchoring proteins that regulate cardiac remodeling. AB - In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation-contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multiprotein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function. PMID- 22075672 TI - Xanthogranulomatous osteomyelitis. AB - Xanthogranulomatous osteomyelitis is a rare type of inflammatory process which is characterized by composition of immune cell aggregation on histological studies. Delayed-type hypersensitivity reaction of cell-mediated immunity may be implicated in its pathogenesis. Gross and radiological examination can mimic malignancy, and differentiation should be confirmed by histopathological evaluation. We describe the case of a 14-year-old Afghan boy presenting with pain in right shoulder and left leg with prior history of trauma. Fever, limitation in right shoulder range of motion, and tenderness in right shoulder and left thigh were detected following examination. Mild leukocytosis, elevated alkaline phosphatase, and increased erythrocyte sedimentation rate with negative C reactive protein (CRP) were revealed. X-ray imaging showed mixed density, periosteal reaction, and cortical disruption. Computed tomography (CT) scan revealed lesions involving medulla and cortex, periosteal reaction with soft tissue component, and bone marrow infiltration in right humerus and left fibula. On magnetic resonance imaging (MRI), signal abnormalities in medulla, metaphysis, and diaphysis of the left fibula associated with cortical irregularity and diffuse soft tissue hypersignal areas were demonstrated. Finally, xanthogranulomatous osteomyelitis was confirmed by histological sample. The clinical manifestations and radiographic and laboratory findings of this rare condition are discussed. PMID- 22075673 TI - Management of anterior cruciate ligament rupture in patients aged 40 years and older. AB - The aim of anterior cruciate ligament (ACL) reconstruction is essentially to restore functional stability of the knee and to allow patients to return to their desired work and activities. While in the young and active population, surgery is often the best therapeutic option after an ACL tear, ACL reconstruction in middle aged people is rather more controversial due to concerns about a higher complication rate. The purpose of our article is to establish, through a systematic review of the literature, useful decision-making criteria for the management of anterior cruciate ligament rupture in patients aged 40 years and older, guiding surgeons to the most appropriate therapeutic approach. Various reports have shown excellent results of ACL reconstruction in patients over the age of 40 in terms of subjective satisfaction, return to previous activity level, and reduced complication and failure rates. Some even document excellent outcomes in subjects of 50 years and older. Although there are limited high-level studies, data reported in the literature suggest that ACL reconstruction can be successful in appropriately selected, motivated older patients with symptomatic knee instability who want to return to participating in highly demanding sport and recreational activities. Deciding factors are based on occupation, sex, activity level of the subject, amount of time spent performing such highly demanding activities, and presence of associated knee lesions. Physiological age and activity level are more important than chronological age as deciding factors when considering ACL reconstruction. PMID- 22075674 TI - Post-surgical tympanostomy tube follow up with audiology: experience at the Freeman Hospital. AB - BACKGROUND: Tympanostomy tube (grommet) insertion is a common procedure, with little guidance in the current literature regarding post-operative surveillance. Our institution implemented a protocol to follow up post-surgical grommet patients via audiology at six weeks. METHODS: A retrospective audit of all patients less than 16 years old who had undergone grommet insertion during a three-month period. RESULTS: A total of 149 patients had grommets inserted. Exclusion criteria left a cohort of 123 individuals; 82 (67 per cent) were followed up by audiology. Of these, 13 (11 per cent) did not attend follow up, and were discharged; 53 (43 per cent) were discharged from audiology with normal thresholds; and 16 (13 per cent) were referred back to a consultant. Therefore, the overall reduction in patients followed up by an otolaryngologist was 54 per cent. CONCLUSION: We recommend a six-week follow up with audiology following grommet insertion, allowing for referral back to ENT services in the event of related complications. PMID- 22075675 TI - Why we need nurse practitioner emergency specialty certification. PMID- 22075676 TI - Diagnosing and treating mild traumatic brain injury in children. AB - Review of recent evidence with translation to practice for the advanced practice nurse role is presented using a case study format for "Mild Traumatic Brain Injury in Children." This "short review" describes the state of the science regarding diagnosis and treatment of mild traumatic brain injury in children, demonstrating multiple challenges to synthesizing existing research into practice guidelines. Implications of this lack of clear research evidence on advanced practice nursing are discussed along with suggestions for using alternative sources of evidence. PMID- 22075677 TI - Differential diagnosis of acute heart failure: brain versus heart. AB - Arrhythmias to transient cardiac failure have been reported in aneurysmal subarachnoid hemorrhage. The cardiac dysfunction can mimic an acute myocardial infarction, and in the presence of severe neurological compromise, careful observation is needed to differentiate the etiology of cardiac failure. Accurate history, rapid assessment, and interpretation of diagnostics are essential to determine the accurate diagnosis and in identifying appropriate treatment. PMID- 22075678 TI - Pharmacologic management during therapeutic hypothermia. AB - Out-of-hospital cardiac arrest continues to be associated with high morbidity and mortality as the mortality rate has been documented to be as high as 90% in patients who experience the insult at home. For those who survive, more than 50% will have some form of brain damage. Despite the devastation of this event, therapeutic options for improving outcomes in this population are unfortunately limited. However, therapeutic hypothermia has been evaluated in 2 landmark randomized, controlled trials in patients who experienced an out-of-hospital cardiac arrest with the results showing an improvement in both neurologic outcomes and mortality. Providers must be familiar with the rationale behind the therapy, the physiological effects of the cooling and rewarming processes, and the pharmacologic management that aides in improved outcomes and minimizes complications. PMID- 22075680 TI - The case of the cutaneous quandary. AB - Early diagnosis of an adverse cutaneous drug reaction (ACDR) is the key to preventing a more severe and life-threatening drug reaction. ACDRs can range from mild rashes to life-threatening events. ACDRs are classified as immunologic and nonimmunologic etiologies. Drug hypersensitivity is an immune mediated response. True hypersensitivity adverse drug reactions mimic many disease states and can involve any organ system (S. ). A thorough history is critical when the patient presents with systemic symptoms in addition to a dermatological response that does not display common distributions and lesions. Medications previously prescribed and taken by patients may produce a delayed immune mediated response that can result in multiorgan syndrome, Stevens-Johnson syndrome, or toxic epidermal necrolysis. PMID- 22075681 TI - Occupational and demographic factors associated with violence in the emergency department. AB - Violence against health care workers is a serious and growing problem. The objectives of this cross-sectional study were to (a) describe the frequency of workplace violence (WPV) against emergency department (ED) workers; (b) identify demographic and occupational characteristics related to WPV; and (c) identify demographic and occupational characteristics related to feelings of safety and level of confidence when dealing with WPV. Survey data were collected from 213 workers at 6 hospital EDs. Verbal and physical violence was prevalent in all 6 EDs. There were no statistically significant differences in the frequency of violence for age, job title, patient population, and hospital location. Sexual harassment was the only category of violence affected by gender with females having a greater frequency. Feelings of safety were positively related to the frequency of WPV. Females were significantly more likely to feel unsafe and have less confidence in dealing with WPV. The study findings indicate that all ED workers are at risk of violence, regardless of personal and occupational characteristics. Feelings of safety are related to job satisfaction and turnover. Violence has serious consequences for the employers, employees, and patients. It is recommended that administration, managers, and employees collaborate to develop and implement prevention strategies to reduce and manage the violence. PMID- 22075682 TI - Therapeutic hypothermia initiated in the pre-hospital setting: a meta-analysis. AB - After resuscitation of the cardiac arrest patient, reperfusion to the brain begins a cascade of events that may lead to permanent brain damage. Cooling suppresses the inflammatory response related to ischemia and metabolic demand, improving oxygen supply to anoxic areas. Until recently, cooling was only performed in the hospital setting. Recent studies have questioned whether initiating the cooling process immediately after resuscitation is beneficial in the pre-hospital setting. The primary purpose of this study was to examine the feasibility and safety of pre-hospital hypothermia via data extraction from randomized controlled trials and statistical meta-analysis. Studies included in this analysis did show a significant statistical difference with the ability to lower the body temperature when beginning pre-hospital cooling immediately, making it feasible to start therapeutic hypothermia in the pre-hospital setting. Further research is needed to determine neurological and discharge outcomes as the studies were not powered to determine statistical significance. PMID- 22075683 TI - Level 2 and level 3 patients in emergency severity index triage system: comparison of characteristics and resource utilization. AB - There is a lack of studies examining distinctions between patients assigned to Level 2 (high risk) and Level 3 (lower risk) in the 5-level ESI triage system. Describing patients assigned to Level 2 and Level 3 may identify unique characteristics related to chief complaint, interventions, and resource needs. A convenience sample of triage nurses was recruited from 2 emergency department (ED) sites. If, at the completion of the patient-nurse triage interaction, the nurse assigned the patient to either Level 2 or Level 3, additional clinical data related to that patient were collected from the ED medical record. Eighteen triage nurses participated in the study with 334 nurse-patient triage interactions collected. Patients presenting with a chief complaint of nausea and vomiting or having a medical history of renal insufficiency/failure were significantly more often assigned to Level 2 than to Level 3 (p = 0.036 and p = 0.013, respectively). Patients assigned to Level 2 were more likely to utilize cardiac monitoring, electrocardiogram, medications, and specialty consultation than patients assigned to Level 3. It is critical that nurses in the triage setting be aware of possible patient factors and resource needs that could influence assignment to specific triage levels. PMID- 22075684 TI - Identifying factors inhibiting or enhancing family presence during resuscitation in the emergency department. AB - The purpose of this qualitative study was to explore inhibitors and enhancing factors surrounding the practice of allowing family presence in the emergency room. Staff and physician interviews were transcribed and decoded for themes. A visual model was built to depict the results. Inhibitors and enhancing factors included the following drivers: staff emotions, personalizing the patient, seeing/hearing everything, closure, emotional support of the family, and "if it were me." The following staff needs were also identified as important issues that needed to be addressed before practice could change further: staff education, optimize environment for privacy, and implementation of a family liaison. The use of qualitative research methods was effective in identifying organizational barriers to transition of evidence into practice. PMID- 22075685 TI - Characteristics of patients who return to the emergency department within 72 hours in one community hospital. AB - This study identifies characteristics of patients who return to the emergency department (ED) within 72 hr after an initial visit. An exploratory quantitative descriptive study was conducted to identify characteristics of patients with unscheduled 72 hr ED returns. The sample consisted of all patients with 72 hr ED return visits for the month of January 2009 at the study facility. Data were collected from electronic patient records utilizing the National Hospital Ambulatory Medical Care Survey instrument modified to eliminate patient identifiers. There were 169 individuals who had at least one 72 hr return visit to the ED for a total of 393 initial and return ED visits. The most common diagnoses were for gastrointestinal complaints. Over a third of the patients who returned had chronic health conditions. There were more emergency department return visits in individuals who lacked access to primary care. PMID- 22075686 TI - "Here comes Santa Claus": what is the evidence? AB - The purpose of this article is to examine the strength of evidence regarding our holiday Santa Claus (SC) practices and the opportunities for new descriptive, correlation, or experimental research on SC. Although existing evidence generally supports SC, in the end we may conclude, "the most real things in the world are those that neither children nor men can see" (Church, as cited in Newseum, n.d.). PMID- 22075687 TI - Obesity epidemics: inevitable outcome of globalization or preventable public health challenge? PMID- 22075688 TI - On the benefit of magnetic magnesium nanocarrier in cardiovascular toxicity of aluminum phosphide. AB - The present study was designed to determine the effect of a new (25)Mg(2+) carrying nanoparticle ((25)MgPMC16) on energy depletion, oxidative stress, and electrocardiographic (ECG) parameters on heart tissue of the rats poisoned by aluminum phosphide (AlP). (25)MgPMC16 at doses of 0.025, 0.05, and 0.1 median lethal dose (LD50 = 896 mg/kg) was administered intravenously (iv) 30 min after a single intragastric administration of AlP (0.25 LD50). Sodium bicarbonate (Bicarb; 2 mEq/kg, iv) was used as the standard therapy. After anesthesia, the animals were rapidly connected to an electronic cardiovascular monitoring device for monitoring of ECG, blood pressure (BP), and heart rate (HR). Later lipid peroxidation, antioxidant power, ATP/ADP ratio, and Mg concentration in the heart were evaluated. Results indicated that after AlP administration, BP and HR decreased while R-R duration increased. (25)MgPMC16 significantly increased the BP and HR at all doses used. We found a considerable increase in antioxidant power, Mg level in the plasma and the heart and a reduction in lipid peroxidation and ADP/ATP ratio at various doses of (25)MgPMC16, but (25)MgPMC16-0.025 + Bicarb was the most effective combination therapy. The results of this study support that (25)MgPMC16 can increase heart energy by active transport of Mg inside the cardiac cells.(25)MgPMC16 seems ameliorating AlP-induced toxicity and cardiac failure necessitating further studies. PMID- 22075689 TI - Application of low magnetic field on inulinase production by Geotrichum candidum under solid state fermentation using leek as substrate. AB - This study evaluates the application of low magnetic field (LMF) on inulinase enzyme production by Geotrichum candidum under solid state fermentation (SSF) using leek as potential carbon source. First, the fermentation conditions were optimized using normal magnetic field grown microorganism. Among eight G. candidum isolates, the most effective strain called G. candidum OC-7 was selected to use in further experiments. In the second part of the study, SSF was carried out under different LMFs (4 and 7 mT). The results showed that inulinase activity was strongly affected by LMF application. The highest enzyme activity was obtained as 535.2 U/g of dry substrate (gds) by 7 mT magnetic field grown G. candidum OC-7. On the contrary, the control had only 412.1 U/gds. Consequently, the use of leek presents a great potential as an alternative carbon source for inulinase production and magnetic field treatment could effectively be used in order to enhance the enzyme production. PMID- 22075690 TI - Antiapoptotic and proliferative activity of curcumin on ovarian follicles in mice exposed to whole body ionizing radiation. AB - The aim of this study was to evaluate the antiapoptotic and proliferative activity of curcumin (Cur) on the ovarian follicles in mice exposed to whole body ionizing radiation (Rd). The mice were exposed to 8.3 gray whole body Rd, and Cur groups were given as a daily dose of 100 mg/kg of Cur for 10 days (10 days before Rd). The ovaries were collected 3 and 12 h after irradiation. To date, no such studies have been performed on antiapoptotic and proliferative activity of Cur on the ovarian follicles in mice exposed to whole body Rd. Analysis of mice ovary after exposure to Rd by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling showed that there were apoptotic cells both in the follicular wall and the antrum, and that the number of follicles showing early atresic features was high 3 h after Rd. On the other hand, analysis of mice ovary 12 h after exposure to Rd showed that the number of follicles containing apoptotic cells with advanced atresic features was significantly higher when compared to the 3-h Rd exposure group. The proliferating cell nuclear antigen -positive granulosa cells were decreased in association with follicular atresia. The groups given treatment were observed to have some benefit from Cur against the damage caused by Rd. The results of this study demonstrate that Cur prevents follicular atresia in Rd-induced apoptosis in ovarian follicles. PMID- 22075691 TI - Thin-filament length correlates with fiber type in human skeletal muscle. AB - Force production in skeletal muscle is proportional to the amount of overlap between the thin and thick filaments, which, in turn, depends on their lengths. Both thin- and thick-filament lengths are precisely regulated and uniform within a myofibril. While thick-filament lengths are essentially constant across muscles and species (~1.65 MUm), thin-filament lengths are highly variable both across species and across muscles of a single species. Here, we used a high-resolution immunofluorescence and image analysis technique (distributed deconvolution) to directly test the hypothesis that thin-filament lengths vary across human muscles. Using deltoid and pectoralis major muscle biopsies, we identified thin filament lengths that ranged from 1.19 +/- 0.08 to 1.37 +/- 0.04 MUm, based on tropomodulin localization with respect to the Z-line. Tropomodulin localized from 0.28 to 0.47 MUm further from the Z-line than the NH(2)-terminus of nebulin in the various biopsies, indicating that human thin filaments have nebulin-free, pointed-end extensions that comprise up to 34% of total thin-filament length. Furthermore, thin-filament length was negatively correlated with the percentage of type 2X myosin heavy chain within the biopsy and shorter in type 2X myosin heavy chain-positive fibers, establishing the existence of a relationship between thin-filament lengths and fiber types in human muscle. Together, these data challenge the widely held assumption that human thin-filament lengths are constant. Our results also have broad relevance to musculoskeletal modeling, surgical reattachment of muscles, and orthopedic rehabilitation. PMID- 22075692 TI - Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. AB - Uncoupling protein (UCP)-1 expressed in brown adipose tissue plays an important role in thermogenesis. Recent data suggest that brown-like adipocytes in white adipose tissue (WAT) and skeletal muscle play a crucial role in the regulation of body weight. Understanding of the mechanism underlying the increase in UCP-1 expression level in these organs should, therefore, provide an approach to managing obesity. The thyroid hormone (TH) has profound effects on mitochondrial biogenesis and promotes the mRNA expression of UCP in skeletal muscle and brown adipose tissue. However, the action of TH on the induction of brown-like adipocytes in WAT has not been elucidated. Thus we investigate whether TH could regulate UCP-1 expression in WAT using multipotent cells isolated from human adipose tissue. In this study, triiodothyronine (T(3)) treatment induced UCP-1 expression and mitochondrial biogenesis, accompanied by the induction of the CCAAT/enhancer binding protein, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and nuclear respiratory factor-1 in differentiated human multipotent adipose-derived stem cells. The effects of T(3) on UCP-1 induction were dependent on TH receptor-beta. Moreover, T(3) treatment increased oxygen consumption rate. These findings indicate that T(3) is an active modulator, which induces energy utilization in white adipocytes through the regulation of UCP-1 expression and mitochondrial biogenesis. Our findings provide evidence that T(3) serves as a bipotential mediator of mitochondrial biogenesis. PMID- 22075693 TI - ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins. AB - Ca(2+)-activated Cl(-) channels (CaCCs) participate in numerous physiological functions such as neuronal excitability, sensory transduction, and transepithelial fluid transport. Recently, it was shown that heterologously expressed anoctamins ANO1 and ANO2 generate currents that resemble native CaCCs. The anoctamin family (also called Tmem16) consists of 10 members, but it is not known whether all members of the family are CaCCs. Expression of ANOs 3-7 in HEK293 cells did not generate Cl(-) currents activated by intracellular Ca(2+), as determined by whole cell patch clamp electrophysiology. With the use of confocal imaging, only ANO1 and ANO2 traffic to the plasma membrane when expressed heterologously. Furthermore, endogenously expressed ANO7 in the human prostate is predominantly intracellular. We took a chimeric approach to identify regions critical for channel trafficking and function. However, none of the chimeras of ANO1 and ANO5/7 that we made trafficked to the plasma membrane. Our results suggest that intracellular anoctamins may be endoplasmic reticulum proteins, although it remains unknown whether these family members are CaCCs. Determining the role of anoctamin family members in ion transport will be critical to understanding their functions in physiology and disease. PMID- 22075694 TI - Lithium interactions with Na+-coupled inorganic phosphate cotransporters: insights into the mechanism of sequential cation binding. AB - Type IIa/b Na(+)-coupled inorganic phosphate cotransporters (NaPi-IIa/b) are considered to be exclusively Na(+) dependent. Here we show that Li(+) can substitute for Na(+) as a driving cation. We expressed NaPi-IIa/b in Xenopus laevis oocytes and performed two-electrode voltage-clamp electrophysiology and uptake assays to investigate the effect of external Li(+) on their kinetics. Replacement of 50% external Na(+) with Li(+) reduced the maximum transport rate and the rate-limiting plateau of the P(i)-induced current began at less hyperpolarizing potentials. Simultaneous electrophysiology and (22)Na uptake on single oocytes revealed that Li(+) ions can substitute for at least one of the three Na(+) ions necessary for cotransport. Presteady-state assays indicated that Li(+) ions alone interact with the empty carrier; however, the total charge displaced was 70% of that with Na(+) alone, or when 50% of the Na(+) was replaced by Li(+). If Na(+) and Li(+) were both present, the midpoint potential of the steady-state charge distribution was shifted towards depolarizing potentials. The charge movement in the presence of Li(+) alone reflected the interaction of one Li(+) ion, in contrast to 2 Na(+) ions when only Na was present. We propose an ordered binding scheme for cotransport in which Li(+) competes with Na(+) to occupy the putative first cation interaction site, followed by the cooperative binding of one Na(+) ion, one divalent P(i) anion, and a third Na(+) ion to complete the carrier loading. With Li(+) bound, the kinetics of subsequent partial reactions were significantly altered. Kinetic simulations of this scheme support our experimental data. PMID- 22075697 TI - Circadian variation of the response of T cells to antigen. AB - Circadian clocks regulate many important aspects of physiology, and their disturbance leads to various medical conditions. Circadian variations have been found in immune system variables, including daily rhythms in circulating WBC numbers and serum concentration of cytokines. However, control of immune functional responses by the circadian clock has remained relatively unexplored. In this study, we show that mouse lymph nodes exhibit rhythmic clock gene expression. T cells from lymph nodes collected over 24 h show a circadian variation in proliferation after stimulation via the TCR, which is blunted in Clock gene mutant mice. The tyrosine kinase ZAP70, which is just downstream of the TCR in the T cell activation pathway and crucial for T cell function, exhibits rhythmic protein expression. Lastly, mice immunized with OVA peptide loaded dendritic cells in the day show a stronger specific T cell response than mice immunized at night. These data reveal circadian control of the Ag-specific immune response and a novel regulatory mode of T cell proliferation, and may provide clues for more efficient vaccination strategies. PMID- 22075696 TI - Contact-dependent T cell activation and T cell stopping require talin1. AB - T cell-APC contact initiates T cell activation and is maintained by the integrin LFA-1. Talin1, an LFA-1 regulator, localizes to the immune synapse (IS) with unknown roles in T cell activation. In this study, we show that talin1-deficient T cells have defects in contact-dependent T cell stopping and proliferation. Although talin1-deficient T cells did not form stable interactions with APCs, transient contacts were sufficient to induce signaling. In contrast to prior models, LFA-1 polarized to T cell-APC contacts in talin1-deficient T cells, but vinculin and F-actin polarization at the IS was impaired. These results indicate that T cell proliferation requires sustained, talin1-mediated T cell-APC interactions and that talin1 is necessary for F-actin polarization and the stability of the IS. PMID- 22075695 TI - Altered neurotransmitter release machinery in mice deficient for the deubiquitinating enzyme Usp14. AB - Homozygous ataxic mice (ax(J)) express reduced levels of the deubiquitinating enzyme Usp14. They develop severe tremors by 2-3 wk of age, followed by hindlimb paralysis, and death by 6-8 wk. While changes in the ubiquitin proteasome system often result in the accumulation of ubiquitin protein aggregates and neuronal loss, these pathological markers are not observed in the ax(J) mice. Instead, defects in neurotransmission were observed in both the central and peripheral nervous systems of ax(J) mice. We have now identified several new alterations in peripheral neurotransmission in the ax(J) mice. Using the two-microelectrode voltage clamp technique on diaphragm muscles of ax(J) mice, we observed that under normal neurotransmitter release conditions ax(J) mice lacked paired-pulse facilitation and exhibited a frequency-dependent increase in rundown of the end plate current at high-frequency stimulation (HFS). Combined electrophysiology and styryl dye staining revealed a significant reduction in quantal content during the initial and plateau portions of the HFS train. In addition, uptake of styryl dyes (FM dye) during HFS demonstrated that the size of the readily releasable vesicle pool was significantly reduced. Destaining rates for styryl dyes suggested that ax(J) neuromuscular junctions are unable to mobilize a sufficient number of vesicles during times of intense activity. These results imply that ax(J) nerve terminals are unable to recruit a sufficient number of vesicles to keep pace with physiological rates of transmitter release. Therefore, ubiquitination of synaptic proteins appears to play an important role in the normal operation of the neurotransmitter release machinery and in regulating the size of pools of synaptic vesicles. PMID- 22075698 TI - CARMA1 is necessary for optimal T cell responses in a murine model of allergic asthma. AB - CARMA1 is a lymphocyte-specific scaffold protein necessary for T cell activation. Deletion of CARMA1 prevents the development of allergic airway inflammation in a mouse model of asthma due to a defect in naive T cell activation. However, it is unknown if CARMA1 is important for effector and memory T cell responses after the initial establishment of inflammation, findings that would be more relevant to asthma therapies targeted to CARMA1. In the current study, we sought to elucidate the role of CARMA1 in T cells that have been previously activated. Using mice in which floxed CARMA1 exons can be selectively deleted in T cells by OX40-driven Cre recombinase (OX40(+/Cre)CARMA1(F/F)), we report that CD4(+) T cells from these mice have impaired T cell reactivation responses and NF-kappaB signaling in vitro. Furthermore, in an in vivo recall model of allergic airway inflammation that is dependent on memory T cell function, OX40(+/Cre)CARMA1(F/F) mice have attenuated eosinophilic airway inflammation, T cell activation, and Th2 cytokine production. Using MHC class II tetramers, we demonstrate that the development and maintenance of Ag-specific memory T cells is not affected in OX40(+/Cre)CARMA1(F/F) mice. In addition, adoptive transfer of Th2-polarized OX40(+/Cre)CARMA1(F/F) Ag-specific CD4(+) T cells into wild-type mice induces markedly less airway inflammation in response to Ag challenge than transfer of wild-type Th2 cells. These data demonstrate a novel role for CARMA1 in effector and memory T cell responses and suggest that therapeutic strategies targeting CARMA1 could help treat chronic inflammatory disorders such as asthma. PMID- 22075700 TI - A novel bacterial resistance mechanism against human group IIA-secreted phospholipase A2: role of Streptococcus pyogenes sortase A. AB - Human group IIA-secreted phospholipase A(2) (sPLA(2)-IIA) is a bactericidal molecule important for the innate immune defense against Gram-positive bacteria. In this study, we analyzed its role in the host defense against Streptococcus pyogenes, a major human pathogen, and demonstrated that this bacterium has evolved a previously unidentified mechanism to resist killing by sPLA(2)-IIA. Analysis of a set of clinical isolates demonstrated that an ~500-fold higher concentration of sPLA(2)-IIA was required to kill S. pyogenes compared with strains of the group B Streptococcus, which previously were shown to be sensitive to sPLA(2)-IIA, indicating that S. pyogenes exhibits a high degree of resistance to sPLA(2)-IIA. We found that an S. pyogenes mutant lacking sortase A, a transpeptidase responsible for anchoring LPXTG proteins to the cell wall in Gram positive bacteria, was significantly more sensitive (~30-fold) to sPLA(2)-IIA compared with the parental strain, indicating that one or more LPXTG surface proteins protect S. pyogenes against sPLA(2)-IIA. Importantly, using transgenic mice expressing human sPLA(2)-IIA, we showed that the sortase A-mediated sPLA(2) IIA resistance mechanism in S. pyogenes also occurs in vivo. Moreover, in this mouse model, we also showed that human sPLA(2)-IIA is important for the defense against lethal S. pyogenes infection. Thus, we demonstrated a novel mechanism by which a pathogenic bacterium can evade the bactericidal action of sPLA(2)-IIA and we showed that sPLA(2)-IIA contributes to the host defense against S. pyogenes infection. PMID- 22075699 TI - Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. AB - Age-related adiposity has been linked to chronic inflammatory diseases in late life. To date, the studies on adipose tissue leukocytes and aging have not taken into account the heterogeneity of adipose tissue macrophages (ATMs), nor have they examined how age impacts other leukocytes such as T cells in fat. Therefore, we have performed a detailed examination of ATM subtypes in young and old mice using state of the art techniques. Our results demonstrate qualitative changes in ATMs with aging that generate a decrease in resident type 2 (M2) ATMs. The profile of ATMs in old fat shifts toward a proinflammatory environment with increased numbers of CD206(-)CD11c(-) (double-negative) ATMs. The mechanism of this aging-induced shift in the phenotypic profile of ATMs was found to be related to a decrease in peroxisome proliferator-activated receptor-gamma expression in ATMs and alterations in chemokine/chemokine receptor expression profiles. Furthermore, we have revealed a profound and unexpected expansion of adipose tissue T cells in visceral fat with aging that includes a significant induction of regulatory T cells in fat. Our findings demonstrate a unique inflammatory cell signature in the physiologic context of aging adipose tissue that differs from those induced in setting of diet-induced obesity. PMID- 22075701 TI - SOCS3 deletion in B cells alters cytokine responses and germinal center output. AB - B cell behavior is fine-tuned by internal regulatory mechanisms and external cues such as cytokines and chemokines. Suppressor of cytokine signaling 3 (SOCS3) is a key regulator of STAT3-dependent cytokine responses in many cell types and has been reported to inhibit CXCL12-induced retention of immature B cells in the bone marrow. Using mice with SOCS3 exclusively deleted in the B cell lineage (Socs3(Delta/Delta)mb1cre(+)), we analyzed the role of SOCS3 in the response of these cells to CXCL12 and the STAT3-inducing cytokines IL-6 and IL-21. Our findings refute a B cell-intrinsic role for SOCS3 in B cell development, because SOCS3 deletion in the B lineage did not affect B cell populations in naive mice. SOCS3 was strongly induced in B cells stimulated with IL-21 and in plasma cells exposed to IL-6. Its deletion permitted excessive and prolonged STAT3 signaling following IL-6 stimulation of plasma cells and, in a T cell-dependent immunization model, reduced the number of germinal center B cells formed and altered the production of Ag-specific IgM and IgE. These data demonstrate a novel regulatory signal transduction circuit in plasma cells, providing, to our knowledge, the first evidence of how these long-lived, sessile cells respond to the external signals that mediate their longevity. PMID- 22075703 TI - Electron-spin motion: a new tool to study ferromagnetic films and surfaces. AB - When electrons are interacting with a ferromagnetic material, their spin polarization vector is expected to move. This spin motion, comprising an azimuthal precession and a polar rotation about the magnetization direction of the ferromagnet, has been studied in spin-polarized electron scattering experiments both in transmission and reflection geometry. In this review we show that electron-spin motion can be considered as a new tool to study ferromagnetic films and surfaces and we discuss its application to a number of different problems: (a) the transmission of spin-polarized electrons across ferromagnetic films, (b) the influence of spin-dependent gaps in the electronic band structure on the spin motion in reflection geometry, (c) interference experiments with spin polarized electrons and (d) the influence of lattice relaxations in ferromagnetic films on the spin motion. PMID- 22075702 TI - Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-gamma dependent mechanism. AB - Dendritic cells (DCs) encompass a heterogeneous population of cells capable of orchestrating innate and adaptive immune responses. The ability of DCs to act as professional APCs has been the foundation for the development and use of these cells as vaccines in cancer immunotherapy. DCs are also endowed with the nonconventional property of directly killing tumor cells. The current study investigates the regulation of murine DC cytotoxic function by T lymphocytes. We provide evidence that CD4(+) Th-1, but not Th-2, Th-17 cells, or regulatory T cells, are capable of inducing DC cytotoxic function. IFN-gamma was identified as the major factor responsible for Th-1-induced DC tumoricidal activity. Tumor cell killing mediated by Th-1-activated killer DCs was dependent on inducible NO synthase expression and NO production. Importantly, Th-1-activated killer DCs were capable of presenting the acquired Ags from the killed tumor cells to T lymphocytes in vitro or in vivo. These observations offer new possibilities for the application of killer DCs in cancer immunotherapy. PMID- 22075704 TI - The induction of rat spermatogonial stem cells into neuronal-like cells and behavioral recovery following transplantation in a rat Parkinson's disease model. AB - Parkinson's disease (PD) is a widespread age-associated neurodegenerative disorder. Current treatment is symptomatic rather than curative. However, stem cell replacement therapies may have the potential to offer curative treatment. In this study, we demonstrate that rat CD49f+ spermatogonial stem cells (rSSCs) can be induced to become functional dopaminergic neuron-like cells in vitro. Furthermore, when rSSCs were transplanted into 6-hydroxydopamine (6-OHDA)-treated PD rats, the results indicated that rSSCs expressed multiple neuron cell markers and were ameliorative to behavioral recovery in PD rats after induction both in vitro and in vivo. In addition, rSSCs demonstrated increased activity in the regeneration of dopaminergic neuron-like cells, increased migration distances and were associated with improvement in animal behavior in the PD rat model. Therefore, rSSCs could be a source of dopaminergic neuron-like cells with potential benefit in cell replacement therapy for PD. PMID- 22075705 TI - Role of endothelin receptor signalling in squamous cell carcinoma. AB - Endothelin plays important roles in various physiological functions including vascular constriction. Recent studies reported that the endothelin receptors ETA and ETB are highly expressed in lung and skin tumor tissues. In contrast, there are few reports on endothelin signalling in the proliferation of head and neck cancer. We found that both ETA and ETB endothelin receptors were overexpressed in tumor cells of tongue cancer samples by immunohistochemistry. ETA and ETB were expressed in cultured lingual and esophageal squamous cell carcinoma (SCCs) cell lines. When both cultured cell lines were treated with an ETA selective antagonist (BQ123) or an ETB selective antagonist (BQ788), inhibition of cell growth was observed. Similar results were observed when SCCs were treated with specific siRNA for the suppression of ETA or ETB. Furthermore, inhibition of the mitogen-activated protein (MAP) kinase pathway by the treatments with ET receptor antagonists and siRNA was also observed. These results indicate that endothelin signalling may, in part, play important roles in cell growth in SCCs through the MAP kinase pathway. PMID- 22075707 TI - Antimicrobial susceptibility of Escherichia coli isolated from feces of wild cranes migrating to Kagoshima, Japan. AB - Susceptibility to 13 antimicrobial agents was examined for 138 Escherichia coli isolates obtained from 192 fecal samples of wild cranes that migrated for wintering to the Izumi plain, Kagoshima prefecture in Japan. The numbers of isolates that were resistant to the antimicrobials used in this study are as follows: oxytetracycline (OTC), 22 isolates; minocycline, 7 isolates; ampicillin (ABPC), 4 isolates; nalidixic acid, 4 isolates; enrofloxacin, 2 isolates; kanamycin, one isolate. Multidrug resistant isolates exhibiting 2-4 drug resistances were obtained. All of the OTC-resistant isolates carried either the tet (A) or tet(B) gene. The bla(TEM) gene was found in all of the ABPC-resistant isolates. PMID- 22075706 TI - Studies on calcium release and H2O2 level produced by the elicitor induced plant cell by fluorescence probing. AB - Using fluorescence probing technology, we studied the mechanism and interrelations of calcium release and H(2)O(2) production in situ in living tissues of tobacco and cotton plants which were induced by pathogen elicitor, salicylic acid (SA) and pectinase respectively. Results showed that (1) pathogen elicitors could induced H(2)O(2) response in epidermis cells regardless of environmental calcium, but in mesophyll protoplast, H(2)O(2) response could only be induced at calcium condition. Similarly, SA and pectinase induced H(2)O(2) response could only be observed at calcium condition; (2) pathogen elicitors could induce calcium response in both epidermis cells and protoplasts regardless of environmental calcium, while calcium response couldn't be induced at non calcium condition by SA and pectinase; (3) H(2)O(2) response and calcium response in protoplast were faster than that in the whole cell. These results indicated that pathogen elicitors can induce the release of cell wall calcium and the cell wall calcium release is independent to pectinase. And it is concluded that free calcium influx is necessary for the oxidative burst and cell wall calcium has an irreplaceable role in defense signal transduction. PMID- 22075708 TI - Comparative studies on the distribution and population of immunocompetent cells in bovine hemal node, lymph node and spleen. AB - The distribution and population of immunocompetent cells in bovine hemal node, mesenteric lymph node and spleen were analyzed comparatively by immunohistochemistry and flow cytometry. Many CD8(+) cells, CD172a(+) cells and gammadelta T cells were found in the lymphatic cord along the sinus of the hemal node and the splenic red pulp. A few CD8(+) cells and gammadelta T cells were distributed diffusely in the paracortex and medullary cord of the mesenteric lymph node. Many germinal centers were recognized in the lymphatic regions such as the cortex and white pulp of these lymphoid organs. The populations of CD8(+) cells and gammadelta T cells in the hemal node and the spleen were higher than those of the mesenteric lymph node. In addition, the populations of CD21(+) cells and MHC class II(+) cells in the hemal node and the mesenteric lymph node were higher than those of the spleen. The results suggest that the hemal node has an important role in both cellular and humoral immunity as well as the lymph node and the spleen in cattle. PMID- 22075709 TI - Situation of serum antibodies against Newcastle disease virus in slaughter-age ostriches after vaccination campaign in Japan. AB - A total of 516 slaughter-age ostrich sera were collected in Japan during 2006 2009. Sixty-one of five hundred and sixteen were positive by virus neutralization (VN) test and the titer of most positive samples was low level. Within the 61 positive sera, 35 sera were collected from unvaccinated ostriches. This result implies that these ostriches might have been infected naturally with low-virulent Newcastle disease virus (NDV). Within the 455 negative samples, 125 samples were from vaccinated ostriches. Since ostrich farmers use live attenuated vaccines, it is reasonable that the titer decreased to below detection level by 1 or 1.5 year old. The above data indicate that NDV has infiltrated into ostrich farms in Japan, and that the efficacy of ostrich ND vaccination is often time-limited. PMID- 22075710 TI - The 2010 foot-and-mouth disease epidemic in Japan. AB - Foot-and-mouth disease (FMD) occurred recently for the first time in a decade in Japan. The index case was detected on a beef-breeding farm in Miyazaki Prefecture, Southern Japan, on April 20, 2010. After confirmation of this first case, control measures such as stamping out, movement restriction and disinfection were implemented. However, these strategies proved insufficient to prevent the spread of FMD and emergency vaccination was adopted. Up until the last outbreak on July 4, 2010, a total of 292 outbreaks had been confirmed, with about 290,000 animals having been culled. The epidemic occurred in an area with a high density of cattle and pigs, making disease control difficult. Invasion of the disease into a high-density area aided its rapid spread and led to difficulties in locating suitable burial sites. Epidemiological investigations indicated that the disease was introduced into Japan approximately one month before detection. This delay in initial detection is considered to have allowed an increased number of outbreaks in the early stage of the epidemic. Nevertheless, the epidemic was contained within a localized area in Miyazaki Prefecture and was eradicated within three months because of intensive control efforts including emergency vaccination. Although this epidemic devastated the livestock industry in Japan, many lessons can be learnt for the future prevention and control of infectious diseases in animals. PMID- 22075711 TI - Dose-response effects of an aqueous formulation of calcitriol and evaluation of renal function in nonpregnant cows. AB - Dose responses of plasma calcitriol, calcium (Ca), bone metabolic markers and glomerular filtration rate (GFR) were evaluated in four nonpregnant Holstein cows treated subcutaneously with an aqueous formulation of calcitriol at four doses in a 4 * 4 Latin-square design. Calcitriol, Ca, and markers of bone metabolism were analyzed in plasma samples. GFR was measured in predose and day 5 samples. Plasma calcitriol and Ca concentrations increased dose-dependently. The calcitriol dose was positively correlated with the area under the concentration-time curve of plasma calcitriol. Bone formation markers tended to increase from day 3 onward for all doses. No significant changes in GFR were noted. Thus, exogenous calcitriol administered between 0.0625 and 0.5 ug/kg body weight elicited dose dependent increases in both plasma calcitriol and Ca and elevated bone formation markers without affecting renal function in nonpregnant cows. PMID- 22075712 TI - Downregulation of miR-221/222 sensitizes glioma cells to temozolomide by regulating apoptosis independently of p53 status. AB - A previous study showed that miR-221/222 can regulate cell apoptosis. p53 is a well known tumor suppressor which can influence the chemosensitivity of glioma cells. However, the effect of miR-221/222 in gliomas with different p53 status is unknown. Here, we demostrate that knockdown of miR-221/222 increases apoptosis in human gliomas of different p53 types (U251 cells, p53 mutant-type; LN308 cells, p53 null-type; and U87 cells, p53 wild-type). Furthermore, the effect of miR 221/22 caused no change of p53 expression in the glioma cells studied. In addition, when a specific siRNA against p53 was employed in U87 cells, no attenuation of apoptosis was found after knockdown of miR-221/222. Importantly, we found that As-miR-221/222-treated cells increased expression of Bax, cytochrome c, Apaf-1 and cleaved-caspase-3. Our results showed that low expression of miR-221/222 sensitized glioma cells to temozolomide (TMZ); in addition, ectopic expression of PUMA by pcDNA-PUMA had a similar effect. Taken together, our study indicates that downregulated miR-221/222 can sensitize glioma cells to TMZ by regulating apoptosis independently of p53 status. PMID- 22075714 TI - Growing fatty mass in the back: diagnosis of a multiple symmetric lipomatosis (Madelung's disease) in association with chronic alcoholism. PMID- 22075716 TI - Age-related changes in pre- and postmenopausal women investigated with 18F fluoride PET--a preliminary study. AB - OBJECTIVE: To evaluate the relationship between age and regional skeletal uptake at sites consisting of either predominantly trabecular or cortical bone using (18)F-fluoride positron emission tomography (PET) in pre- and postmenopausal women. MATERIALS AND METHODS: Thirty-two women (40.6 +/- 12.3 years; age range 25 72 years) were assigned to one of two groups: group 1 comprised 22 premenopausal women (33 +/- 6.5 years; age range 25-48 years) and group 2 comprised 10 postmenopausal women (56 +/- 6.7 years; age range 49-72 years). The maximum standardized uptake value (SUVmax) was determined from the lumbar spine and the humeral shaft. Student's t-test for each unpaired dataset was used to evaluate statistical differences between the two groups. The SUVmax values for the humeral shaft and the lumbar spine were compared with aging. RESULTS: The SUVmax (mean +/ SD) was 1.2 +/- 0.5 in the humeral shaft and 4.7 +/- 1.0 in the lumbar spine. The SUVmax in the humeral shaft correlated significantly with advancing age (r = 0.67, P < 0.01). The SUVmax in the lumbar spine declined significantly with advancing age (r = -0.50, P < 0.01). The humeral shaft of women in group 1 exhibited a significantly lower SUVmax compared to that in group 2 (1.1 +/- 0.4 versus 1.6 +/- 0.6; P < 0.05). On the other hand, the lumbar spine of women in group 1 exhibited a significantly higher SUVmax compared to that in group 2 (5.1 +/- 0.7 versus 4.0 +/- 1.1; P < 0.05). The mean SUVmax in the lumbar spine was 2.5 times greater than that in the humeral shaft in group 2. CONCLUSION: Semiquantitative analysis with (18)F-fluoride PET might be a useful tool for analyzing age-related changes in pre- and postmenopausal women. PMID- 22075718 TI - Inhibition of HERG1 K+ channel protein expression decreases cell proliferation of human small cell lung cancer cells. AB - HERG (human ether-a-go-go-related gene) K(+) currents fulfill important ionic functions in cardiac and other excitable cells. In addition, HERG channels influence cell growth and migration in various types of tumor cells. The mechanisms underlying these functions are still not resolved. Here, we investigated the role of HERG channels for cell growth in a cell line (SW2) derived from small cell lung cancer (SCLC), a malignant variant of lung cancer. The two HERG1 isoforms (HERG1a, HERG1b) as well as HERG2 and HERG3 are expressed in SW2 cells. Inhibition of HERG currents by acute or sustained application of E 4031, a specific ERG channel blocker, depolarized SW2 cells by 10-15 mV. This result indicated that HERG K(+) conductance contributes considerably to the maintenance of the resting potential of about -45 mV. Blockage of HERG channels by E-4031 for up to 72 h did not affect cell proliferation. In contrast, siRNA induced inhibition of HERG1 protein expression decreased cell proliferation by about 50%. Reduction of HERG1 protein expression was confirmed by Western blots. HERG current was almost absent in SW2 cells transfected with siRNA against HERG1. Qualitatively similar results were obtained in three other SCLC cell lines (OH1, OH3, H82), suggesting that the HERG1 channel protein is involved in SCLC cell growth, whereas the ion-conducting function of HERG1 seems not to be important for cell growth. PMID- 22075719 TI - A 5-year follow-up study of Alfredson's heel-drop exercise programme in chronic midportion Achilles tendinopathy. AB - BACKGROUND: Eccentric exercises have the most evidence in conservative treatment of midportion Achilles tendinopathy. Although short-term studies show significant improvement, little is known of the long-term (>3 years) results. AIM: To evaluate the 5-year outcome of patients with chronic midportion Achilles tendinopathy treated with the classical Alfredson's heel-drop exercise programme. STUDY DESIGN: Part of a 5-year follow-up of a previously conducted randomised controlled trial. Methods 58 patients (70 tendons) were approached 5 years after the start of the heel-drop exercise programme according to Alfredson. At baseline and at 5-year follow-up, the validated Victorian Institute of Sports Assessment Achilles (VISA-A) questionnaire score, pain status, alternative treatments received and ultrasonographic neovascularisation score were recorded. RESULTS: In 46 patients (58 tendons), the VISA-A score significantly increased from 49.2 at baseline to 83.6 after 5 years (p<0.001) and from the 1-year to 5-year follow-up from 75.0 to 83.4 (p<0.01). 39.7% of the patients were completely pain-free at follow-up and 48.3% had received one or more alternative treatments. The sagittal tendon thickness decreased from 8.05 mm (SD 2.1) at baseline to 7.50 mm (SD 1.6) at the 5-year follow-up (p=0.051). CONCLUSION: At 5-year follow-up, a significant increase of VISA-A score can be expected. After the 3-month Alfredson's heel-drop exercise programme, almost half of the patients had received other therapies. Although improvement of symptoms can be expected at long term, mild pain may remain. PMID- 22075720 TI - Detecting gustatory-olfactory flavor mixtures: models of probability summation. AB - Odorants and flavorants typically contain many components. It is generally easier to detect multicomponent stimuli than to detect a single component, through either neural integration or probability summation (PS) (or both). PS assumes that the sensory effects of 2 (or more) stimulus components (e.g., gustatory and olfactory components of a flavorant) are detected in statistically independent channels, that each channel makes a separate decision whether a component is detected, and that the behavioral response depends solely on the separate decisions. Models of PS traditionally assume high thresholds for detecting each component, noise being irrelevant. The core assumptions may be adapted, however, to signal-detection theory, where noise limits detection. The present article derives predictions of high-threshold and signal-detection models of independent decision PS in detecting gustatory-olfactory flavorants, comparing predictions in yes/no and 2-alternative forced-choice tasks using blocked and intermixed stimulus designs. The models also extend to measures of response times to suprathreshold flavorants. Predictions derived from high-threshold and signal detection models differ markedly. Available empirical evidence on gustatory olfactory flavor detection suggests that neither the high-threshold nor the signal-detection versions of PS can readily account for the results, which likely reflect neural integration in the flavor system. PMID- 22075721 TI - Highlight: the degenerating Y chromosome: under the pressures of sex and selection. PMID- 22075722 TI - Detection of pristine gas two billion years after the Big Bang. AB - In the current cosmological model, only the three lightest elements were created in the first few minutes after the Big Bang; all other elements were produced later in stars. To date, however, heavy elements have been observed in all astrophysical environments. We report the detection of two gas clouds with no discernible elements heavier than hydrogen. These systems exhibit the lowest heavy-element abundance in the early universe, and thus are potential fuel for the most metal-poor halo stars. The detection of deuterium in one system at the level predicted by primordial nucleosynthesis provides a direct confirmation of the standard cosmological model. The composition of these clouds further implies that the transport of heavy elements from galaxies to their surroundings is highly inhomogeneous. PMID- 22075723 TI - Protostellar feedback halts the growth of the first stars in the universe. AB - The first stars fundamentally transformed the early universe by emitting the first light and by producing the first heavy elements. These effects were predetermined by the mass distribution of the first stars, which is thought to have been fixed by a complex interplay of gas accretion and protostellar radiation. We performed radiation-hydrodynamics simulations that followed the growth of a primordial protostar through to the early stages as a star with thermonuclear burning. The circumstellar accretion disk was evaporated by ultraviolet radiation from the star when its mass was 43 times that of the Sun. Such massive primordial stars, in contrast to the often-postulated extremely massive stars, may help explain the fact that there are no signatures of the pair instability supernovae in abundance patterns of metal-poor stars in our galaxy. PMID- 22075724 TI - Inhibitory plasticity balances excitation and inhibition in sensory pathways and memory networks. AB - Cortical neurons receive balanced excitatory and inhibitory synaptic currents. Such a balance could be established and maintained in an experience-dependent manner by synaptic plasticity at inhibitory synapses. We show that this mechanism provides an explanation for the sparse firing patterns observed in response to natural stimuli and fits well with a recently observed interaction of excitatory and inhibitory receptive field plasticity. The introduction of inhibitory plasticity in suitable recurrent networks provides a homeostatic mechanism that leads to asynchronous irregular network states. Further, it can accommodate synaptic memories with activity patterns that become indiscernible from the background state but can be reactivated by external stimuli. Our results suggest an essential role of inhibitory plasticity in the formation and maintenance of functional cortical circuitry. PMID- 22075725 TI - Interconversion between intestinal stem cell populations in distinct niches. AB - Intestinal epithelial stem cell identity and location have been the subject of substantial research. Cells in the +4 niche are slow-cycling and label-retaining, whereas a different stem cell niche located at the crypt base is occupied by crypt base columnar (CBC) cells. CBCs are distinct from +4 cells, and the relationship between them is unknown, though both give rise to all intestinal epithelial lineages. We demonstrate that Hopx, an atypical homeobox protein, is a specific marker of +4 cells. Hopx-expressing cells give rise to CBCs and all mature intestinal epithelial lineages. Conversely, CBCs can give rise to +4 Hopx positive cells. These findings demonstrate a bidirectional lineage relationship between active and quiescent stem cells in their niches. PMID- 22075726 TI - Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum infected erythrocytes. AB - The hemoglobins S and C protect carriers from severe Plasmodium falciparum malaria. Here, we found that these hemoglobinopathies affected the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that the parasite generated a host derived actin cytoskeleton within the cytoplasm of wild-type red blood cells that connected the Maurer's clefts with the host cell membrane and to which transport vesicles were attached. The actin cytoskeleton and the Maurer's clefts were aberrant in erythrocytes containing hemoglobin S or C. Hemoglobin oxidation products, enriched in hemoglobin S and C erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria. PMID- 22075727 TI - Highly diastereoselective and enantioselective Michael addition of 5H-oxazol-4 ones to alpha,beta-unsaturated ketones catalyzed by a new bifunctional organocatalyst with broad substrate scope and applicability. AB - A new thiourea-tertiary amine bifunctional catalyst derived from L-tert-leucine was developed and provides excellent stereocontrol in a novel and direct Michael addition of 5H-oxazol-4-ones to alpha,beta-unsaturated ketones with much broad substrate scope. The conjugate addition products with chiral vicinal quaternary and tertiary stereocenters can be easily transformed to structurally interesting compounds or building blocks. PMID- 22075728 TI - Characteristics of spinal cord stroke in clinical neurology. AB - Spinal cord stroke accounts for about 0.3% of all strokes in our department. Thirty-two patients (15 males, 17 females; mean age 63.3 years) treated in the period 1995-2010 were included. Patients underwent thorough investigation including the use of different stroke scales (National Institute of Health Stroke Scale, Barthel Index and modified Rankin Scale). Twenty-eight patients had infarctions, 3 had hemorrhages, and 1 had arterio-venous fistula. Twenty-eight spinal cord strokes were spontaneous, 2 were secondary to aorta aneurysms, and 2 post surgery. Biphasic ictus was seen in 17% of all spontaneous infarctions. Younger age, male gender, hypertension, diabetes mellitus, and higher blood glucose on admission regardless of diabetes mellitus, were risk factors associated with more severe spinal cord stroke. Treatment and prevention of these risk factors should be essential in spinal cord stroke. We recommend a clinical classification into upper (cervical) and lower (thoracic or medullary conus) spinal cord strokes. Patients with upper strokes in this study had more severe strokes initially, but they had a better prognosis. Therefore it is important to identify this patient group.Acute sensory spinal cord deficit symptoms, common initial symptoms in biphasic spinal cord strokes, should be considered as possible spinal cord stroke, especially when preceded by radiating pain between the shoulders. PMID- 22075729 TI - Preparation and formation mechanism of a n-butylammonium/MnO2 layered hybrid via a one-pot synthesis under moderate conditions. AB - The preparation of organic/inorganic layered hybrids has relied on multistep processing. Thus, shortening the synthetic procedure is important for possible future applications, but only a few studies report one-pot syntheses. In this work, we established a simple one-pot solution process to synthesize layered alkyl ammonium/MnO(2) hybrids, by stirring MnCl(2) and alkyl amine/H(2)O(2) aqueous solutions at 40 degrees C; the reaction concept is a chemical oxidation of Mn(II) ions in the presence of alkyl amine in aqueous solution. Furthermore, the formation mechanism of the layered n-butylammonium/MnO(2) hybrid was examined by following the structural and optical changes during the reaction, revealing that the one-pot reaction includes 3 steps; formation of beta-MnOOH, topotactic oxidation of beta-Mn(III)OOH to form the protonated layered manganese oxide H(x)Mn(III, IV)O(2).yH(2)O, and ion-exchange of interlayer H(+) (or H(3)O(+)) with n-butylammonium to form layered n-butylammonium/MnO(2). PMID- 22075730 TI - Ventral compression in adult patients with Chiari 1 malformation sans basilar invagination: cause and management. AB - BACKGROUND: A small subset of patients with adult Chiari I malformation without basilar invagination (BI) and instability show ventral cervicomedullary distortion/compression and have symptoms pertaining to that. The cause of this ventral compression remains speculative. Additionally, it is unclear if these patients would require ventral decompression with posterior fusion or only posterior decompression would suffice. METHODS: Sixteen adult patients with Chiari I malformation with significant ventral cervicomedullary compression, in the absence of BI, were included in the study. Atlantoaxial dislocation (AAD) was excluded in these patients by flexion-extension craniovertebral junction X-rays and computed tomography (CT). Their clinical profile, especially symptoms pertaining to cervicomedullary compression, i.e. dysphagia, dysarthria and spasticity, were graded. The ventral cervicomedullary compression (VCMC) was quantified using pBC2 (maximum perpendicular distance to the basion-infero posterior point of the C2 body) on sagittal magnetic resonance imaging (MRI) and only those patients with pBC2 >=9 mm were included. Furthermore, retroversion of dens and retro odonotid tissue thickness was calculated in each patient. Fifteen patients underwent posterior decompression alone and one refused surgery. Follow up was done every 3 months. Repeat MRI was done at 1 year following surgery to look for pBC2. RESULTS: The mean pBC2 was 11 +/- 0.2 mm. Retroversion of dens was responsible for VCMC in three patients and periodontoid crown in 13. There was no correlation between the tonsillar descent, age and the pBC2. All patients improved in symptoms of cervicomedullary compression following surgery. One patient worsened 6 months after initial improvement. The pBC2 did not change, as seen on follow-up MRI done in five patients. CONCLUSIONS: VCMC in adult patients with Chiari I malformation in the absence of BI and/or AAD is due to periodontoid tissue (crown) or retroverted dens. Though a long-term study is required, it appears that all patients with Chiari I malformation, irrespective of the VCMC, can be given a chance with posterior decompression alone. Transoral decompression with posterior fusion may be required in a small subset of patients who fail to improve or worsen following posterior decompression only. PMID- 22075732 TI - The subdiaphragmatic cistern: historic and radioanatomic findings. AB - BACKGROUND: In the past, sporadic demonstrations of the existence of a subarachnoid subdiaphragmatic cistern have been published. The aim of this study was to evaluate the anatomical characteristics of the subdiaphragmatic cistern of the pituitary gland. METHODS: After a complete review of the literature published on the topic, we report anatomical observations of the subdiaphragmatic cistern and its relationship to the pituitary gland and to the chiasmatic cistern. Ten cadaveric heads were studied using different techniques and surgical methods (plastination, plastic casts of the subarachnoid spaces, microscopic and transsphenoidal endoscopic approaches). Moreover, 3-T magnetic resonance images of ten healthy volunteers were analyzed to investigate the presence and anatomical variability of the subdiaphragmatic cistern. RESULTS: By means of our qualitative radioanatomic study, we found that the roof of the subdiaphragmatic cistern is formed by the diaphragma sellae, the floor by the superior face of the pituitary gland, the lateral walls by the arachnoidea extending laterally through the medial walls of the cavernous sinus, and the medial walls by the infundibular stem. The subdiaphragmatic cistern communicates by means of the ostium of the diaphragm with the chiasmatic cistern. CONCLUSION: We confirmed the existence of the subdiaphragmatic cistern. The overused term "suprasellar cistern" refers more to a complex of cisterns, formed by the subdiaphragmatic cistern, below the diaphragma sella, and by the chiasmatic cistern, above it, in direct communication with the lamina terminalis and carotid cisterns. PMID- 22075733 TI - Are routine methods good enough to stain senile plaques and neurofibrillary tangles in different brain regions of demented patients? AB - INTRODUCTION: Numerous clinical cases have been reported showing the clinical picture of dementia but not meeting the neuropathological criteria for Alzheimer's dementia (AD). Different methods used to stain senile plaques (SPs) and neurofibrillary tangles (NFTs) might account for this discrepancy. SUBJECTS AND METHODS: Here, brains of 11 patients with dementia were examined. Cryosections and paraffin sections from 6 different brain regions (frontal medial, temporal medial and occipital gyrus, hippocampus, superior parietal lobe and cerebellum) of all cases were stained with Bielschowsky, Campbell, Gallyas and Congo red stains each. RESULTS: The study shows that the Bielschowsky silver stain is insufficient for detecting SPs and NFTs, whereas two other methods proved to be more accurate. SPs were found in similar frequency in all brain regions examined (exception: cerebellum). The highest amount was shown with Campbell silver stain in paraffin sections. In Congo red only 25 percent of these SPs were stained, which is probably due to a great number of them not containing any amyloid. NFTs were found almost exclusively in the hippocampus. The highest number was detected with Gallyas silver stain in cryosections. CONCLUSION: These results may suggest that Campbell stain for SPs and Gallyas stain for NFTs should be the methods routinely used. PMID- 22075734 TI - Cardiovascular risk factors as potential markers for mild cognitive impairment and Alzheimer's disease. AB - BACKGROUND: Mild cognitive impairment (MCI) is an early stage of cognitive decline that has a significant risk of converting to dementia. Cardiovascular pathology appears to have a major impact in cognitive decline, and it is clear that early identification and correction of cardiovascular morbidity could have a major impact on cognitive functioning. SUBJECTS AND METHODS: Our study was conducted in order to identify some cardiovascular risk factors among patients with cognitive decline (MCI or Alzheimer disease-AD) and to find if there is any correlation with the degree of cognitive decline. We evaluated the body mass index, total cholesterol, hypertension, history of smoking, alcohol consumption and diabetes mellitus in patients with MCI and AD, compared with an age-matched control group. RESULTS: Regarding the body mass index, we observed a progressive decrease in patients with MCI and AD, in comparison with the control group. Similar aspects were also observed in the case of cholesterol levels, only that post hoc analysis revealed no significantly statistical differences between MCI and AD groups. The systolic blood pressure was increased in the patients with MCI and AD. Also, as in the case of cholesterol levels, post hoc analysis revealed no significantly statistical differences between MCI and AD groups. Pearson's correlation showed significant connections between the cardiovascular risk factors and the results of the cognitive evaluation. CONCLUSIONS: Our results constitute additional evidence that cardiovascular risk factors are involved in cognitive regression. This finding could have an important impact on the management of dementia. PMID- 22075735 TI - The MMPI-2 neurotic triad subscales and depression levels after pharmacological treatment in patients with depressive disorders - clinical study. AB - BACKGROUND: Affective disorders provide for one third of the main causes of psychiatric inpatient care, both in male and female subjects. An early diagnosis of the disease with precise identification of the character of its particular symptoms are key important factors for the efficacy of treatment. The goal of the study was an identification of possible associations between scores of the neurotic triad in the MMPI-2 test (hypochondria - Hs, depression - D, hysteria - Hy), evaluated at initial hospitalization period with remission degree assessed by the Hamilton Depression Rating Scale (HDRS), following eight weeks of treatment with SSRI. SUBJECTS AND METHODS: A group of 50 subjects took part in the study. The MMPI-2 test and HDRS were used in the study. The HDRS was performed at the therapy onset and reapplied after 8 weeks of its continuation. The MMPI-2 test was applied at the beginning of treatment. RESULTS: Higher scores in Hs (p=0.007), D (p=0.021) and Hy scales (p=0.001) are associated with the higher degree of depression, measured by the HDRS at the therapy onset. The highest performance in Hs scale (p=0.003) and Hy scale (p=0.001) evaluated on admission, was associated with the highest depression level after pharmacological treatment. CONCLUSION: The higher the degree of hypochondria and hysteria symptoms, measured by the MMPI-2 test at the onset of therapy in patients with depressive disorders, the higher severity of depression is being found after 8 weeks of therapy with SSRI agents, measured by the HDRS scale. PMID- 22075736 TI - Quantitative electroencephalography in schizophrenia and depression. AB - BACKGROUND: Standard (qualitative) electroencephalography (EEG) is routinely used in the diagnostic evaluation of psychiatric patients. Quantitative EEG (qEEG) findings differ between patients with schizophrenia, patients with depression, but results are not consistent. The aim of our study was to determine the differences in qEEG parameters between patients with schizophrenia, patients with depression, and healthy subjects. SUBJECTS AND METHODS: The study included 30 patients with schizophrenia, 33 patients with depression, and 30 healthy subjects. All study participants underwent standard EEG. Artifact-free 100-second epochs were selected from the recorded material and analyzed with Fast Fourier Transformation (FFT) analysis. RESULTS: The results are presented as absolute spectral power values (MUV2) of delta, theta, alpha, and beta components of the EEG spectrum. EEGs were recorded from 12 locations including Fp1, Fp2, F3, F4, F7, F8, T3, T4, P3, P4, O1, and O2. In comparison with healthy subjects, patients with schizophrenia showed increased delta, theta, and beta activity and decreased alpha activity. Similar results were obtained in patients with depression, but in fewer regions. In patients with schizophrenia, delta power over Fp1, Fp2, F4, and F8 regions was increased in comparison with those in patients with depression. Interhemispheric asymmetry was found in patients with schizophrenia and healthy subjects, but not in patients with depression. CONCLUSION: The finding that patients with schizophrenia differed from patients with depression in delta power values could be potentially used in differential diagnosis between schizophrenia and depression. The role of qEEG in clinical differentiation between these two mental disorders may be especially important in cases of negative-symptom schizophrenia. PMID- 22075737 TI - Serum Brain-derived neurotrophic factor (BDNF): the severity and symptomatic dimensions of depression. AB - INTRODUCTION: The aim of this study was to compare the concentration of serum Brain-derived neurotrophic factor (BDNF) in patients suffering from major depressive disorder (MDD) considering the severity of MDD episode defined by the Hamilton rating scale for depression (HAMD-17). The other aim was to research the connection between serum BDNF and the symptomatic dimensions of MDD. SUBJECTS AND METHODS: The study includes 139 participants with major depressive disorder (MDD). Diagnosis of MDD was set by DSM-IV-TR criteria. The severity of MDD was estimated with HAM-D-17 in the manner that mild episode was diagnosed if the score on HAMD-17 was up to 18, moderately severe 18-25 and severe over 25. Concentration of BDNF was determined by the ELISA method. RESULTS: This research could not find a difference in BDNF concentration considering the severity of the depressive disorder in groups suffering from mild, moderately severe and severe episodes of MDD (F=1.816; p=0.169). Factor analysis of HAMD-17 extracted four dimensions of depressive symptoms. None of the symptomatic dimensions was significantly related to BDNF concentration. CONCLUSION: Results of this study indicate that serum BDNF levels are not related to the severity of depression and its specific symptomatic dimensions. These findings support the idea of a complex relationship between BDNF concentration at the periphery and in the CNS. PMID- 22075738 TI - Depressive symptoms in patients with hepatitis C treated with pegylated interferon alpha therapy: a 24-week prospective study. AB - OBJECTIVE: To prospectively evaluate depressive symptoms and risk factors for depression in patients with chronic hepatitis C (CHC) treated with pegylated interferon alpha therapy combined with oral ribavirin (PEG-IFN-alpha+RBV) and to analyze self-rating scale for depression in comparison to observer-based scale in the given population. SUBJECTS AND METHODS: The Hamilton Depression Rating Scale and Zung Self Rating Depression Scale were used to screen for depressive symptoms in 74 subjects with CHC before PEG- IFN-alpha (mean dose 152.6+/-25.6 mcg), and in the follow-up visits (4, 12 and 24 week). RESULTS: Incidence of depressive symptoms in patients (mean age 39.9+/-13.4 years; equal sex distribution p=0.225) treated by PEG- IFN-alpha was the highest on 12th week of the treatment, when more than a 20% of our sample had moderate/severe symptoms of depression, and about 30% had minor depressive symptoms. For the screening of depression during PEG- IFN-alpha self-assessment scale was equally reliable as observer-based assesment of depressive symptoms. Common clinical parameters- subject related risk factors (age (p=0.955 ), sex (p=0.008), lifetime psychiatric disorder (p=0.656)), illness related risk factors (duration of CHC (p=0.267 ), i.v drug aplication as way of transmission (p=0.292)) and therapy-related risk factors (recommended duration of PEG-IFN-alpha (p=0.993) and dose of PEG-IFN-alpha (p=0.841)) were not signifcantly associated with depressive symptoms on PEG-IFN alpha. CONCLUSIONS: Liason-consultation services should collaborate with hepatologists in creating screening programmes, supplemented by objective criteria and guidelines, for early recognition and treatment of interferon induced depression. PMID- 22075739 TI - The effects of beverage type on suicide rate in Russia. AB - BACKGROUND: Research evidence has suggested that the consumption of different types of alcoholic beverage may have a differential effect on suicide rate. The aim of this study was to examine the relation between the consumption of different beverage types and suicide rates in Russia. SUBJECTS AND METHODS: Age standardized sex- and age-specific suicide rate for the period 1980-2005 and data on beverage-specific alcohol sale were obtained from the Russian State Statistical Committee. Time-series analytical modeling techniques (ARIMA) were used to examine the relationship between the sale of different alcoholic beverages and suicide rates. RESULTS: Vodka consumption as measured by sale was significantly associated with both male and female suicide rate. The consumption of beer and wine were not associated with suicide rate. The estimates of the age specific models for men were positive (except for the 75+ age group) and ranging from 0.069 (60-74 age group) to 0.123 (30-44 age group). The estimates for women were positive for the 15-29 age group (0.08), 30-44 age group (0.096) and 45-59 age group (0.057). CONCLUSIONS: These findings suggest that public health efforts should focus on both reducing overall consumption and changing beverage preference away from distilled spirits in order to reduce suicide rate in Russia. PMID- 22075740 TI - First generation antipsychotics switch with Risperidone in the treatment of chronic schizophrenic patients. AB - BACKGROUND: Schizophrenia is a severe chronic psychiatric disorder for which treatment compliance is important in the prevention of relapse. Second generation antipsychotics (SGA), such as Risperidone, have been found to be more effective in the treatment of such patients than the high potency first generation antipsychotics (FGA). This is an open study where the same group of patients was first treated with FGA and then were switched to Risperidone, in controlled hospital conditions, after a wash- out period. The aim of the study was to examine whether patients with schizophrenia who were judged to be stable on long term treatment with FGA would further benefit from a switch to an atypical antipsychotic drug. SUBJECTS AND METHODS: Eighty hospitalized patients suffering from Schizophrenia or Schizoaffective disorder (male 54, female 26) were first treated with Haloperidol (N=60) or Fluphenazine (N=20), and then were switched to Risperidone. Their clinical state was monitored using the PANSS scale for Schizophrenia, measuring the Total PANSS score. The KLAWANS scale for assessment of extrapyramidal syndrome (EPS) was also used. Administration and dosage of Trihexiphenidil (THF) was recorded. The study lasted for 8 weeks, with 4 screenings (Visit 0-baseline- FGA, Visits 1-3 Risperidone on Day 14, 28 and 56, respectively). RESULTS: The average age was 38. Patients usually suffered the paranoid form of Schizophrenia (55%). The duration of illness was more than 5 years (38.8%). During the eight- week trial on Risperidone, using the PANSS total scores, we observed clinical improvement where the therapy switch had caused an initial worsening (p<0.05). Also, the compared baseline (FGA) and last visit showed a low, but statistically significant benefit in favor of Risperidone (t=5.45, df=79, p<0.005). Intensity of EPS measured by KLAWANS scores significantly decreased during time (F=4.115; p=0.016; Partial Eta Square=0.058). Average Trihexiphenidil doses followed Risperidone in a dose dependent manner (r=0.748, r=0.661, respectively, p<0.01) with the consequent decrease of patients needing THF corrective therapy (68.8% at the baseline toward 22.5% on last visit). CONCLUSION: Switch to Risperidone medication provided significant additional improvement in symptom severity, extrapyramidal side effects and need for anticholinergic medication. This suggests that one might expect better compliance in future treatment in this population of chronic schizophrenic patients. PMID- 22075741 TI - Burnout syndrome among physicians - the role of personality dimensions and coping strategies. AB - BACKGROUND: Burnout syndrome (BS) and stress-related disorders are frequent among medical specialists, but it has been suggested that some health workers are more prone to the BS than others. This study assessed the intensity of the BS among 3 groups of physicians: psychiatrists, general practitioners and surgeons and examined correlation both between the intensity of BS and physicians' personality dimensions as well as between the level of BS and stress coping strategies. SUBJECTS AND METHODS: The sample consisted of 160 physicians (70 general practitioners, 50 psychiatrists, 40 surgeons). The assessment was carried out by the Maslach Burnout Inventory, The Temperament and Character Inventory and Manual for the Ways of Coping Questionnaire. RESULTS: Dimension of emotional exhaustion was the most prominent in general practitioners (F=5.546, df1=2, df2=156, p<0.01), while dimension of depersonalization was highest in surgeons (F=15.314, df1=2, df2=156, p<0.01), as well as lack of personal accomplishment (F=16.079, df1=2, df2=156, p<0.01). We found that the Harm Avoidance has lead to development of BS while Self-directedness and Cooperativeness were prominent in physicians with low level of BS. The escape-avoidance was in correlation with high depersonalization and lack of personal accomplishment while self-control was prominent in physicians with lower BS. CONCLUSION: The BS affects personal well being and professional performance. It is important to identify individuals with a tendency towards its development, in order to undertake preventive measures such as stress management and improvement of the stress coping strategies. PMID- 22075742 TI - Teaching health care professionals about suicide safety planning. AB - The suicide safety plan is a plan of action created by the clinician and patient that essentially charts the course of what the patient should do if he/she begins to experience suicidal urges. It is important for clinicians to learn how to implement a safety plan so that they can offer this service to their patients and teach their colleagues and associates about suicide safety planning. The safety plan is a great tool employed to help patients with suicidal urges, but trainees clinicians and clinician associates alike - should fully understand that it is not a form of treatment. However, since an effective treatment for suicidality does not exist, practitioners should definitely use suicide safety planning. Although more resources are now being provided to individuals with suicidal behavior, more research needs to be done to develop new, effective methods of treatment and prevention of suicidal behavior. PMID- 22075743 TI - Infantile masturbation - exclusion of severe diagnosis does not exclude parental distress - case report. PMID- 22075744 TI - [Depression: diagnosis, treatment and course]. AB - Depressions are very common mental diseases. The diagnosis is made by psychopathology criteria and the course of the disorder. There is a growing body to the knowledge about etiology and treatment of depression - neuro-imaging, neuroplasticity, CREB and BDNF are all modified by antidepressants treatment and/or psychotherapy. As differential diagnoses, depressive syndromes on the basis of organic diseases but also burn-out syndromes may play a role, different therapeutic efforts are necessary. The treatment of depression consists of psychopharmacological and psychotherapeutic strategies, combinations of both are useful. Many psychopharmacological substances with differing mechanisms of action are available - combinations of antidepressants with complementing mechanisms are possible. The course of depressions is mainly influenced by "working therapies". Comorbid somatic diseases and their successful treatment are of relevance for the long term course. PMID- 22075745 TI - Depression: a diagnosis aptly used? AB - Depression is a very common mental disorder which often results in relevant negative consequences ranging from impaired quality of life to an increased suicide rate. Unfortunately, non-psychiatric physicians frequently under-diagnose and under-treat depression. Nevertheless, sometime the diagnosis "depression" is used for mentally well and other mental disorders (i.e. sometimes depression is over-diagnosed). Screening tools were suggested to improve the recognition of mental disorders in everyday clinical work. Studies have shown that the criterion validity of usual screening questionnaires such as the Geriatric Depression Scale (GDS) is sufficient, while very short questionnaires consisting of one or two questions must not be used because of high misclassification rates. A meta analysis of randomized trials of screening for depression indicate that screening for depression is probably effective when it is coupled with additional activities such as educational programs for primary care physicians. PMID- 22075746 TI - [The relationship between depression, anxiety and heart disease - a psychosomatic challenge]. AB - BACKGROUND: Depressive and cardiological disorders present a major comorbidity. Their manifold interrelations may be best analysed within a biopsychosocial model of disease. METHODS: A systematic research was done on empirical studies published during the last 15 years and dealing with epidemiological, etiopathogenetic and therapeutic dimensions of the comorbidity of depression, anxiety and heart disease. RESULTS: From an epidemiological perspective recurrent depressions are associated with a significantly increased risk of coronary heart disease. Depressive disorders play a major role in triggering critical cardiac events, e.g. myocardial infarction. The prevalence rates of depressive disorders in various cardiological conditions are significantly higher than the frequencies that can be expected in healthy general population. Depression shows a negative impact on the somatic morbidity and mortality during the further course of illness. Anxiety and posttraumatic stress disorders seem to be interrelated with cardiological conditions in quite a similar way, probably contributing even more negatively to critical and lethal cardiological events than depression. From an etiopathogenetic perspective some clusters of depressive symptoms seem to be linked to cardiotoxicity more closely than other, vital exhaustion, anhedonia, and hopelessness probably mediating a special risk. In any case, postmyocardial infarct depression that proves treatment-resistent indicates a negative prognosis of the prevailing cardiological condition. On a level of psychological and psychosocial constructs type-A personality, anger/hostility, type-D personality, and alexithymia have been explored regarding its proper pathogenetic role. Psychological and psychopathological variables have to be set into a context of psychosocial stressors on the one hand, and have to be simultaneously analysed with various underlying psycho- and neurobiological variables on the other. Above all, HPA- and sympathicomedullary dysfunctions, reduced heart rate variability, altered functions of thrombocytes, and increased proinflammatory processes have to be recognized as significantly contributing to the pathophysiology both of depression and of heart condition. Neurobiological aspects of anxiety and posttraumatic stress disorders must be interlinked with these underpinnings of depression. Differential effects on critical cardiological events must be supposed. From a therapeutic perspective several RCTs demonstrate that SSRIs may safely and efficiently treat depressive disorders in cardiological conditions, and may even improve the general somatic prognosis. Cognitive-behavioural psychotherapies have been empirically validated in treating depression and anxiety with cardiological patients. So far, however, a differential indication of psychopharmacological versus psychotherapeutic approaches has not been proved yet. CONCLUSIONS: Depression and anxiety disorders in patients with heart disease paradigmatically define a psychosomatic-somatopsychic challenge to any health delivery system. A psychosomatic perspective may best be practised within a Consultation-Liaison psychiatric service that cooperates continuously and closely with cardiological departments and experts. PMID- 22075747 TI - [Anterior approach liver resection with the liver hanging maneuver. Technique and indications]. AB - The anterior approach liver resection has advantages compared to conventional liver resection. Mobilization during conventional liver resection may cause local pressure on the tumor which could lead to tumor cell dissemination or even to tumor rupture. Furthermore, hemodynamic parameters tend to deteriorate during mobilization due to compression or twisting of the inferior vena cava. In addition, the left liver lobe often is compressed which can lead to tissue damage of the residual parenchyma. The risk of these complications can be reduced by the anterior approach technique which is facilitated by the so-called liver hanging maneuver. Appropriate indications for this technique are large tumors of the right liver lobe, tumors with infiltration of the right hepatic vein and infiltration of the vena cava from the right side, tumors with infiltration of the diaphragm and tumors of the right lobe after previous resections of the right lobe. PMID- 22075748 TI - RNA interference in Caenorhabditis elegans: uptake, mechanism, and regulation. AB - RNA interference (RNAi) is a powerful research tool that has enabled molecular insights into gene activity, pathway analysis, partial loss-of-function phenotypes, and large-scale genomic discovery of gene function. While RNAi works extremely well in the non-parasitic nematode C. elegans, it is also especially useful in organisms that lack facile genetic analysis. Extensive genetic analysis of the mechanisms, delivery and regulation of RNAi in C. elegans has provided mechanistic and phenomenological insights into why RNAi is so effective in this species. These insights are useful for the testing and development of RNAi in other nematodes, including parasitic nematodes where more effective RNAi would be extremely useful. Here, we review the current advances in C. elegans for RNA delivery methods, regulation of cell autonomous and systemic RNAi phenomena, and implications of enhanced RNAi mutants. These discussions, with a focus on mechanism and cross-species application, provide new perspectives for optimizing RNAi in other species. PMID- 22075750 TI - Qiliqiangxin inhibits the development of cardiac hypertrophy, remodeling, and dysfunction during 4 weeks of pressure overload in mice. AB - Qiliqiangxin (QL), a traditional Chinese medicine, has been used in the treatment of chronic heart failure. However, whether QL can benefit cardiac remodeling in the hypertensive state is unknown. We here examined the effects of QL on the development of cardiac hypertrophy through comparing those of losartan in C57BL/6 mice underlying transverse aorta constriction for 4 weeks. QL and losartan were administrated at 0.6 mg and 13.4 mg.kg.d, respectively. Cardiac hypertrophy, function, and remodeling were evaluated by echocardiography, catheterization, histology, and examination of specific gene expression and ERK phosphorylation. Cardiac apoptosis, autophagy, tumor necrosis factor alpha/insulin-like growth factor-1, and angiotensin II type 1 receptor expression and especially the proliferation of cardiomyocytes and phosphorylation of ErbB receptors were examined in vivo to elucidate the mechanisms. Transverse aorta constriction for 2 weeks resulted in a significant cardiac hypertrophy, which was significantly suppressed by either QL or losartan treatment. At 4 weeks after transverse aorta constriction, although the development of cardiac dysfunction and remodeling and the increases in apoptosis, autophagy, tumor necrosis factor alpha/insulin-like growth factor-1, and angiotensin II type 1 receptor expression were abrogated comparably between QL and losartan treatments, QL, but not losartan, enhanced proliferation of cardiomyocytes, which was paralleled with dowregulation of CCAAT/enhancer-binding protein beta, upregulation of CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4, and increases in ErbB2 and ErbB4 phosphorylation. Furthermore, inhibition of either ErbB2 or CBP/p300 interacting transactivator with ED-rich carboxy-terminal domain 4 abolished the cardiac protective effects of QL. Thus, QL inhibits myocardial inflammation and cardiomyocyte death and promotes cardiomyocyte proliferation, leading to an ameliorated cardiac remodeling and function in a mouse model of pressure overload. The possible mechanisms may involve inhibition of angiotensin II type 1 receptor and activation of ErbB receptors. PMID- 22075749 TI - Combined aliskiren and amlodipine reduce albuminuria via reduction in renal inflammation in diabetic rats. AB - We hypothesized that compared with hydrochlorothiazide (HCTZ), the renin inhibitor aliskiren (ALISK) or amlodipine (AMLO) and their combination reduce albuminuria via reduction in renal inflammation, independent of blood pressure (BP) changes. We studied normal and streptozotocin-induced diabetic (DM) Sprague Dawley rats treated for 6 weeks with vehicle, ALISK, HCTZ, or AMLO individually and combined and evaluated the effects of treatments on BP, urine albumin to creatinine ratio, renal interstitial fluid levels of angiotensin II, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) and renal expression of TNF-alpha, IL-6, transforming growth factor beta 1, and nuclear factor kappa B. There were no differences in BP between treatments. Only ALISK and its combinations reduced renal interstitial fluid angiotensin II. Urine albumin to creatinine ratio increased in DM rats and decreased with ALISK alone or combined with HCTZ or AMLO. HCTZ or AMLO individually and combined did not influence urine albumin to creatinine ratio. Renal interstitial fluid TNF-alpha and IL-6, and the renal expression of TNF-alpha, IL-6, transforming growth factor beta 1, and nuclear factor kappa B were increased in DM rats. These renal inflammatory markers were reduced only with ALISK or AMLO individually or combined with other treatments. We conclude that ALISK alone and combined with HCTZ or AMLO reduced albuminuria in diabetes via reduction in renal inflammation, independent of BP changes. PMID- 22075751 TI - The effect of CYP7A1 polymorphisms on lipid responses to fenofibrate. AB - INTRODUCTION: CYP7A1 encodes cholesterol 7alpha-hydroxylase, an enzyme crucial to cholesterol homeostasis. Its transcriptional activity is downregulated by fenofibrate. The goal of this study was to determine the effect of CYP7A1 polymorphisms on lipid changes in response to fenofibrate. METHODS: We examined the associations of 3 tagging single nuclear polymorphisms (i6782C>T, m204T>G, 3U12536A>C) at CYP7A1 with triglyceride (TG) and high-density lipoprotein cholesterol (HDL)-C responses to a 3-week treatment with 160 mg/d of fenofibrate in 864 US white participants from the Genetics of Lipid Lowering Drugs and Diet Network study. RESULTS: The m204T>G variant was significantly associated with TG and HDL-C responses with fenofibrate. Individuals homozygous for the common T allele of m204T>G single nuclear polymorphism displayed both the greater reduction of TG (-32% for TT, -28% for GT, -25% for GG, P = 0.004) and an increase of HDL-C response compared with noncarriers (4.1% for TT, 3.4% for GT, 1.2% for GG, P = 0.01). Conversely, individuals homozygous for the minor allele of i6782C>T showed a greater increase in the HDL-C response compared with noncarriers (2.8% CC, 4.5% for CT, 5.8% for TT, P = 0.02), albeit no significant effect on TG response. CONCLUSIONS: Our data suggest that common variants at the CYP7A1 locus modulate the TG-lowering and HDL-C-raising effects of fenofibrate, and contribute to the interindividual variation of the drug responses. PMID- 22075752 TI - Heart rate reduction induced by the if current inhibitor ivabradine improves diastolic function and attenuates cardiac tissue hypoxia. AB - AIMS: Enhanced heart rate (HR) is a compensatory mechanism in chronic heart failure (CHF), preserving cardiac output, but at the cost of increased left ventricular (LV) oxygen consumption and impaired diastolic function. The HR reduction (HRR) induced by the If current inhibitor ivabradine prevents LV systolic dysfunction in CHF, but whether HRR improves LV diastolic function is unknown. METHODS: LV diastolic function and remodeling were assessed in rats with CHF after coronary ligation after long-term (90 days, starting 7 days after ligation) and delayed short-term (4 days, starting 93 days after ligation) ivabradine treatment (10 mg.kg.d). RESULTS: Long- and short-term HRR reduced LV end-diastolic pressure, LV relaxation, and LV end-diastolic pressure-volume relation. Simultaneously, LV hypoxia-inducible factor-1alpha expression was reduced. Long-term and, to a more marked extent, short-term HRR increased endothelial cell proliferation, associated after long-term HRR with the prevention of CHF-related LV capillary rarefaction. Long-term and, to a lesser extent, short-term HRR increased endothelial nitric oxide synthase expression, associated after long-term HRR with improved nitric oxide-dependent coronary vasodilatation. CONCLUSIONS: Long-term HRR induced by ivabradine improves diastolic LV function probably involving attenuated hypoxia, reduced remodeling, and/or preserved nitric oxide bioavailability, resulting from processes triggered early after HRR initiation: angiogenesis and/or preservation of endothelial nitric oxide synthase expression. PMID- 22075753 TI - Antimicrobial efficacy of denture adhesives on some oral malodor-related microbes. AB - The objective of the study was to determine the antimicrobial efficacy of three denture adhesives toward Streptococcus oralis, mutans, Prevotella oralis and Fusobacterium nucleatum. Adhesives used were Corega Ultra((r)), Fixodent Pro Original((r)) and Biotene((r)) Denture Grip. For Streptococcus oralis and Streptococcus mutans, four tubes of Trypticase Soy Broth 10 mL and 1 g denture of adhesive were used. In addition four tubes of Trypticase Soy Broth 10 mL without any denture adhesive was employed as control. For Prevotella oralis and Fusobacterium nucleatum, four tubes of thioglycolate 10 mL and 1 g denture adhesive were used for each one, while four tubes of thioglycolate 10 mL without adhesive served as control. All samples were incubated for 48 h at 37 degrees C. After 48 h, the number of colonies was counted and the mean was extracted as cfu/mL. The results were evaluated with ANOVA on ranked data and Tukey's post hoc test at alpha = 0.05. Streptococcus oralis, mutans, Prevotella oralis and Fusobacterium nucleatum showed decreased number of colonies for each denture adhesive compared to the control. Under the conditions of this in vitro study, all the tested denture adhesives showed antimicrobial efficacy. However, in contrast to the hypothesis, there were differences among them. Corega Ultra((r)) and Biotene((r)) Denture Grip were more effective for all the tested oral malodor related microbes than Fixodent Pro Original((r)). PMID- 22075754 TI - Evaluation of fit of cement-retained implant-supported 3-unit structures fabricated with direct metal laser sintering and vacuum casting techniques. AB - This study evaluated the vertical discrepancy of implant-fixed 3-unit structures. Frameworks were constructed with laser-sintered Co-Cr, and vacuum-cast Co-Cr, Ni Cr-Ti, and Pd-Au. Samples of each alloy group were randomly luted in standard fashion using resin-modified glass-ionomer, self-adhesive, and acrylic/urethane based cements (n = 12 each). Discrepancies were SEM analyzed. Three-way ANOVA and Student-Newman-Keuls tests were run (P < 0.05). Laser-sintered structures achieved the best fit per cement tested. Within each alloy group, resin-modified glass-ionomer and acrylic/urethane-based cements produced comparably lower discrepancies than the self-adhesive agent. The abutment position did not yield significant differences. All misfit values could be considered clinically acceptable. PMID- 22075755 TI - Histological and immunohistochemical features of gingival enlargement in a patient with AML. AB - Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells. PMID- 22075756 TI - Defining the role of laboratory genetic counselor. AB - An increasing number of genetic counselors are moving into non-clinical roles, where their primary duties do not involve direct patient contact. According to the National Society of Genetic Counselors Professional Status Survey in 2010, 23% of counselors working in non-clinical roles identified laboratory or genetic testing as their primary area of work. Using a survey, we identified 43 genetic counselors who work predominately in laboratory settings. The two primary tasks performed by participants, include acting as a customer liaison (95%) and calling out test results (88%). Nineteen participants (44.2%) also reported spending a considerable amount of time signing reports. The most prevalent areas of job satisfaction were support from laboratory directors (76.8%), autonomy (76.7%), interactions with clinicians (69.7%) and interaction with other genetics counselors (67.5%). This is the first study specifically looking at the roles of laboratory genetic counselors, which is an expanding area of genetic counseling. PMID- 22075757 TI - Nuclear estrogen receptor-mediated Notch signaling and GPR30-mediated PI3K/AKT signaling in the regulation of endometrial cancer cell proliferation. AB - To elucidate the mechanisms of nuclear estrogen receptor (ER)-mediated and G protein-coupled receptor 30 (GPR30)-mediated signaling in the regulation of proliferation in ER-positive and ER-negative endometrial cancer cells, two human endometrial carcinoma cell lines, Ishikawa (ER-positive) and KLE (ER-negative), were used. PCR and Western blot analyses were used to determine the effects of estrogen stimulation on the activation of Notch and GPR30-PI3K/AKT signaling. Cell growth was investigated using MTT assays. Overexpression of ER in ER negative cells was achieved by plasmid transfection and was used to investigate the effects on cellular growth and Notch signaling. GPR30-mediated signaling was evaluated using siRNA interference. Estrogen stimulated cell proliferation in both cell lines, it activated Notch signaling in ER-positive Ishikawa cells, but not in ER-negative KLE cells. Blockade of this signaling by a Notch inhibitor resulted in partial arrest of estrogen-induced cell proliferation in Ishikawa cells. Overexpression of ER in KLE cells restored estrogen-enhanced Notch signaling and further promoted cell growth. GPR30, as a new G-protein-coupled estrogen receptor, was detected in both cell lines, but was stronger in ER negative KLE cells. Depletion of GPR30 in KLE cells abolished estrogen-induced PI3K/AKT signaling activation and resulted in inhibition of cell proliferation. Conclusively, regulation of proliferation in nuclear ER-positive endometrial cancer cells is mediated by both ER-Notch signaling and GPR30-PI3K/AKT signaling, whereas only the latter pathway is involved in the regulation of growth in nuclear ER-negative endometrial cancer cells. PMID- 22075758 TI - Ripe fruit of Rubus coreanus inhibits mast cell-mediated allergic inflammation. AB - In this study, we investigated the effect of a water extract of the ripe fruits of Rubus coreanus Miq. (Rosaceae) (RFRC) on mast cell-mediated allergic inflammation and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. RFRC dose-dependently inhibited compound 48/80 induced systemic anaphylaxis and serum histamine release in mice. RFRC reduced the immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis. RFRC attenuated histamine release from rat peritoneal mast cells and human mast cells by the reduction of intracellular calcium. RFRC decreased the phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187 (PMACI) stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of RFRC on cytokine production was nuclear factor (NF)-kappaB- and mitogen-activated protein kinase (MAPK)-dependent. In addition, RFRC suppressed the activation of caspase-1. Our findings provide evidence that RFRC inhibits mast cell-derived allergic inflammatory reactions, and for the involvement of calcium, NF-kappaB, MAPKs and caspase-1 in these effects. Furthermore, in vivo and in vitro anti-allergic inflammatory effects of RFRC provide affirmative proof of a possible therapeutic application of this agent in allergic inflammatory diseases. PMID- 22075759 TI - Subaru studies of the cosmic dawn. AB - An overview on the current status of the census of the early Universe population is given. Observational surveys of high redshift objects provide direct opportunities to study the early epoch of the Universe. The target population included are Lyman Alpha Emitters (LAE), Lyman Break Galaxies (LBG), gravitationally lensed galaxies, quasars and gamma-ray bursts (GRB). The basic properties of these objects and the methods used to study them are reviewed. The present paper highlights the fact that the Subaru Telescope group made significant contributions in this field of science to elucidate the epoch of the cosmic dawn and to improve the understanding of how and when infant galaxies evolve into mature ones. PMID- 22075760 TI - Molecular bases of thermophily in hyperthermophiles. AB - I reflect on some of our studies on the hyperthermophilic archaeon, Thermococcus kodakarensis KOD1 and its enzymes. The strain can grow at temperatures up to 100 degrees C, and also represents one of the simplest forms of life. As expected, all enzymes, DNA, RNA, cytoplasmic membrane, and cytoplasmic solute displayed remarkable thermostability, and we have determined some of the basic principles that govern this feature. To our delight, many of the enzymes exhibited unique biochemical properties and novel structures not found in mesophilic proteins. Here, I will focus on some enzymes whose three-dimensional structures are characteristic of thermostable enzymes. I will also add some examples on the stabilization of DNA, RNA, cytoplasmic membrane, and cytoplasmic solute. PMID- 22075761 TI - Flexible antibodies with nonprotein hinges. AB - There is a significant need for antibodies that can bind targets with greater affinity. Here we describe a novel strategy employing chemical semisynthesis to produce symmetroadhesins: antibody-like molecules having nonprotein hinge regions that are more flexible and extendible and are capable of two-handed binding. Native chemical ligation was carried out under mild, non-denaturing conditions to join a ligand binding domain (Abeta peptide) to an IgG1 Fc dimer via discrete oxyethylene oligomers of various lengths. Two-handed Abeta-Fc fusion proteins were obtained in quantitative yield and shown by surface plasmon resonance to bind an anti-Abeta antibody with a K(D) at least two orders of magnitude greater than the cognate Abeta peptide. MALDI-TOF MS analysis confirmed the protein/nonprotein/protein structure of the two-handed molecules, demonstrating its power to characterize complex protein-nonprotein hybrids by virtue of desorption/ionization mediated by peptide sequences contained therein. We anticipate many applications for symmetroadhesins that combine the target specificity of antibodies with the novel physical, chemical and biological properties of nonprotein hinges. PMID- 22075762 TI - Serum IL10, IL12 and circulating CD4+CD25high T regulatory cells in relation to long-term clinical outcome in head and neck squamous cell carcinoma patients. AB - IL10, but not IL12 or T regulatory cells in the circulation of newly presenting, pre-treatment head and neck squamous cell carcinoma (HNSCC) patients, has been shown previously to be related to survival over a mean follow-up period of 15 months. Here, we followed the same patients for a longer period to determine whether these associations change. Pre- and post-treatment serum IL10/IL12 and circulating T regs were measured using ELISA and flow cytometry respectively and were correlated with survival after a 33 month average follow-up in a cohort of newly presenting HNSCC patients (n=107), with cancers of the hypopharynx (n=16), larynx (n=36), oral cavity (n=21), oropharynx (n=25), sinonasal (n=4) or unknown origin (n=5). Although the mean survival time of patients with detectable levels of IL10 pre-treatment was lower (40.6 months) than that of those without detectable levels of IL10 (45.6 months), the difference was no longer significant, in contrast to earlier follow-up data. In conclusion, although serum levels of IL10 may be a prognostic indicator for HNSCC patients over the short term, they become less significant as follow-up time increases. PMID- 22075763 TI - Representation of grasp postures and anticipatory motor planning in children. AB - In this study, we investigated anticipatory motor planning and the development of cognitive representation of grasp postures in children aged 7, 8, and 9 years. Overall, 9-year-old children were more likely to plan their movements to end in comfortable postures, and have distinct representational structures of certain grasp postures, compared to the 7- and 8-year old children. Additionally, the sensitivity toward comfortable end-states (end-state comfort) was related to the mental representation of certain grasp postures. Children with grasp comfort related and functionally well-structured representations were more likely to have satisfied end-state comfort in both the simple and the advanced planning condition. In contrast, end-state comfort satisfaction for the advanced planning condition was much lower for children whose cognitive representations were not structured by grasp comfort. The results of the present study support the notion that cognitive action representation plays an important role in the planning and control of grasp postures. PMID- 22075764 TI - Bidirectional semantic interference between action and speech. AB - Research on embodied cognition assumes that language processing involves modal simulations that recruit the same neural systems that are usually used for action execution. If this is true, one should find evidence for bidirectional crosstalk between action and language. Using a direct matching paradigm, this study tested if action-languages interactions are bidirectional (Experiments 1 and 2), and whether the effect of crosstalk between action perception and language production is due to facilitation or interference (Experiment 3). Replicating previous findings, we found evidence for crosstalk when manual actions had to be performed simultaneously to action-word perception (Experiment 1) and also when language had to be produced during simultaneous perception of hand actions (Experiment 2). These findings suggest a clear bidirectional relationship between action and language. The latter crosstalk effect was due to interference between action and language (Experiment 3). By extending previous research of embodied cognition, the present findings provide novel evidence suggesting that bidirectional functional relations between action and language are based on similar conceptual semantic representations. PMID- 22075765 TI - Monte Carlo simulation of surface segregation phenomena in extended and nanoparticle surfaces of Pt-Pd alloys. AB - The surface segregation phenomena in the extended and nanoparticle surfaces of Pt Pd alloys have been studied using the Monte Carlo (MC) simulation method and the modified embedded-atom method (MEAM) potentials developed for Pt-Pd alloys. The MEAM potentials were fitted to reproduce the experimental values of the lattice parameters, cohesive energies and surface energies of pure Pt and Pd metals, as well as the density functional theory calculation results of the lattice parameters and heat of formation of L1(2) Pt(3)Pd, L1(0) PtPd and L1(2) PtPd(3) crystal. Using the MC method and the developed MEAM potentials, we calculated the Pt concentrations in the outermost three layers of the equilibrium (111), (100) and (110) extended surfaces as well as the outermost surfaces of the equilibrium cubo-octahedral nanoparticles of Pt-Pd alloys. Our simulation results showed that the Pd atoms would segregate into the outermost layers of the extended surfaces and the Pt concentration would increase monotonically from the extended surfaces into the bulk. The equilibrium Pt-Pd nanoparticles were found to have Pd-enriched shells and Pt-enriched cores. In the shell of the Pt-Pd nanoparticles, the Pd atoms were predicted to preferably segregate to the (100) facets rather than the (111) facets. PMID- 22075766 TI - Epstein-barr virus coinfection in cerebrospinal fluid is associated with increased mortality in Malawian adults with bacterial meningitis. AB - Mortality from adult bacterial meningitis exceeds 50% in sub-Saharan Africa. We postulated that-particularly in individuals infected with human immunodeficiency virus (HIV)-herpes simplex virus, varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in the cerebrospinal fluid (CSF) contribute to poor outcome. CSF from 149 Malawian adults with bacterial meningitis and 39 controls were analyzed using polymerase chain reaction. EBV was detected in 79 of 149 bacterial meningitis patients. Mortality (54%) was associated with higher CSF EBV load when adjusted for HIV (P = .01). CMV was detected in 11 of 115 HIV infected patients, 8 of whom died. The mechanisms by which EBV and CMV contribute to poor outcome require further investigation. PMID- 22075767 TI - Rare (<1%) histological subtypes of renal cell carcinoma: an update. AB - Recent advances in genetics and pathology have allowed description of several new histological subtypes of renal cell carcinoma (RCC) as well as better characterization of other rare subtypes. We herein present a comprehensive review of taxonomy, epidemiology, pathology, imaging findings, and natural history of a wide spectrum of rare subtypes of RCCs that individually constitute <1% of all the RCCs. PMID- 22075768 TI - One step synthesis of C-dots by microwave mediated caramelization of poly(ethylene glycol). AB - A rapid, simple and one step microwave mediated method for synthesizing C-dots using poly(ethylene glycol) (PEG) as a precursor and passivating agent is reported. The C-dots possessed low cytotoxicity, were amenable to separation by electrophoresis, photostable and entered cancer cells, making them suitable candidates for bioimaging and biolabelling. PMID- 22075769 TI - Homeless but connected: the role of heterogeneous social network ties and social networking technology in the mental health outcomes of street-living adolescents. AB - Although social integration tends to have positive effects on the mental health of housed adolescents, the role of homeless adolescents' social networks is more ambiguous. Social network data were collected from 136 homeless adolescents in Hollywood, California to examine how network ties are associated with symptoms of anxiety and depression. Face-to-face relationships with street-based peers were a risk factor for both anxiety and depression, while contacting home-based friends through social networking technology was found to be protective for depression. Community-based and public agencies serving homeless adolescents should consider facilitating the maintenance of these protective relationships by providing internet access. PMID- 22075771 TI - Cervical cord atrophy caused by vertebral artery dolichoectasia. PMID- 22075770 TI - Causal Beliefs and Effects upon Mental Illness Identification Among Chinese Immigrant Relatives of Individuals with Psychosis. AB - Identifying factors that facilitate treatment for psychotic disorders among Chinese-immigrants is crucial due to delayed treatment use. Identifying causal beliefs held by relatives that might predict identification of 'mental illness' as opposed to other 'indigenous labels' may promote more effective mental health service use. We examine what effects beliefs of 'physical causes' and other non biomedical causal beliefs ('general social causes', and 'indigenous Chinese beliefs' or culture-specific epistemologies of illness) might have on mental illness identification. Forty-nine relatives of Chinese-immigrant consumers with psychosis were sampled. Higher endorsement of 'physical causes' was associated with mental illness labeling. However among the non-biomedical causal beliefs, 'general social causes' demonstrated no relationship with mental illness identification, while endorsement of 'indigenous Chinese beliefs' showed a negative relationship. Effective treatment- and community-based psychoeducation, in addition to emphasizing biomedical models, might integrate indigenous Chinese epistemologies of illness to facilitate rapid identification of psychotic disorders and promote treatment use. PMID- 22075772 TI - Using ecological frameworks to advance a field of research, practice, and policy on aging-in-place initiatives. AB - Initiatives to promote aging in place have emerged rapidly in the United States across various health care settings (e.g., acute care hospitals, skilled nursing facilities) and broader community settings (e.g., public social service agencies). Moreover, recent federal policies include a growing number of provisions for local efforts to promote aging in place. Despite emerging bodies of research that have described singular initiatives in their own right, there has been very little scholarship that forges conceptual linkages across this increasingly vast domain of research, practice, and policy. Integrative theory development is critical to ensure that aging-in-place initiatives do not become fragmented from each other. This article uses insights from ecological frameworks specifically Urie Bronfenbrenner's bioecological systems theory and M. Powell Lawton's general ecological model of aging-to conceptualize a range of programs as aging-in-place initiatives and for describing their similarities and differences, particularly in terms of the features through which they intend to promote aging in place. Theoretically derived dimensions along which to characterize aging-in-place initiatives include environment-focused aspects (e.g., the types of social systems and structures that the initiatives target for change) and person-focused aspects (e.g., the extent to which the initiatives target particular subgroups of older adults). The article concludes with a discussion on how these theoretically derived dimensions can be used to advance and integrate research, practice, and policy to systematically develop and expand aging-in-place initiatives. PMID- 22075773 TI - Knowledge of and attitudes toward nonpharmacological interventions for treatment of behavior symptoms associated with dementia: a comparison of physicians, psychologists, and nurse practitioners. AB - PURPOSE OF THE STUDY: Behavior problems are common in nursing homes. Current guidelines recommend nonpharmacological interventions (NPHIs) as first-line treatment, but pharmacological regimens (PIs) continue to be used. Given differences in background and training of those who treat behavior problems in residents, we compared attitudes of physicians (MDs), psychologists (PhDs), and nurse practitioners (NPs) concerning PI and NPHI usage as well as knowledge of NPHIs. DESIGN AND METHODS: One hundred and eight MDs, 36 PhDs, and 89 NPs responded to a web-based questionnaire that captured level of agreement with statements concerning treatment of behavior symptoms and familiarity with NPHIs. RESULTS: NPs were the most favorable toward NPHIs. MDs were significantly more favorable to the use of PIs than were PhDs, with attitudes of NPs falling in between. All felt that NPHI usage should increase and that NPHIs should be implemented before using PIs but also believed that PIs work well for behavior problems. MDs had significantly lower knowledge of NPHIs than PhDs or NPs. Overall, NPHI knowledge was similar for PhDs and NPs, although they differed on their use of specific interventions. IMPLICATIONS: As levels of knowledge and familiarity with NPHIs differed among providers, it is conceivable that all might benefit from training and experience with a wider range of NPHIs. Future studies might evaluate the impact of a uniform understanding of NPHI on communication and teamwork in nursing homes and examine ways to enhance a multidisciplinary approach that would allow for the tailoring and individualization that is required of successful interventions. PMID- 22075774 TI - Synovial lesions in experimental canine Lyme borreliosis. AB - Borrelia burgdorferi is the causative agent of Lyme disease, which is mainly characterized by lameness in dogs. More than 95% of naturally infected dogs are asymptomatic or subclinical; however, in experimental studies, histologic synovial lesions are consistently observed in asymptomatic dogs inoculated with B. burdgorferi. This study investigates the ability of a synovial histopathologic scoring system, clinicopathologic data, and polymerase chain reaction (PCR) testing to differentiate between B. burgdorferi-infected and uninfected dogs. Eighteen 18-week-old beagles were subject to challenge with B. burgdorferi infected wild-caught ticks (Ixodes scapularis), and 4 uninfected dogs served as controls. Infection was confirmed by serology (ELISA) and PCR amplification of B. burgdorferi-specific DNA of skin biopsies taken at the tick attachment site. A synovial scoring system from human medicine was adapted and implemented on postmortem synovial samples to discriminate infected and noninfected animals. Application of this system to elbows and stifles with a cumulative joint score cutoff > 4 showed a sensitivity of 88.2% and a specificity of 100%, with a positive likelihood ratio of infinity and a negative likelihood ratio of 0.12. Complete blood count, serum biochemistry, urinalysis, urine protein:creatinine, urine PCR, synovial and lymph node cytology, and synovial PCR were evaluated but were not reliable indicators of clinical disease. PMID- 22075776 TI - A novel herpesvirus in 3 species of pheasants: mountain peacock pheasant (Polyplectron inopinatum), Malayan peacock pheasant (Polyplectron malacense), and Congo peafowl (Afropavo congensis). AB - The mountain peacock pheasant (Polyplectron inopinatum), the Malayan peacock pheasant (Polyplectron malacense), and the Congo peafowl (Afropavo congensis) are all listed as vulnerable to extinction under the International Union for Conservation of Nature Red List of Threatened Species. Here the authors report fatal infection with a novel herpesvirus in all 3 species of birds. DNA was extracted from the livers of birds with hepatocellular necrosis and intranuclear eosinophilic inclusions consistent with herpesvirus infection. Based on degenerate herpesvirus primers and polymerase chain reaction, 220- and 519-base pair products of the herpes DNA polymerase and DNA terminase genes, respectively, were amplified. Sequence analysis revealed that all birds were likely infected with the same virus. At the nucleotide level, the pheasant herpesvirus had 92% identity with gallid herpesvirus 3 and 77.7% identity with gallid herpesvirus 2. At the amino acid level, the herpes virus had 93.8% identity with gallid herpesvirus 3 and 89.4% identity with gallid herpesvirus 2. These findings indicate that the closest relative to this novel herpesvirus is gallid herpesvirus 3, a nonpathogenic virus used widely in a vaccine against Marek's disease. In situ hybridization using probes specific to the peacock pheasant herpesvirus DNA polymerase revealed strong intranuclear staining in the necrotic liver lesions of an infected Malayan peacock pheasant but no staining in normal liver from an uninfected bird. The phasianid herpesvirus reported here is a novel member of the genus Mardivirus of the subfamily Alphaherpesvirinae and is distinct from other galliform herpesviruses. PMID- 22075777 TI - Glucagon-like peptide-1 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro. AB - Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine. Ussing chamber methods, in concert with transmural electrical field stimulation (EFS), were used to study actions on neurogenic chloride secretion. ELISA was used to study GLP-1R effects on neural release of acetylcholine (ACh). Intramural localization of GLP-1R was assessed with immunohistochemistry. Application of GLP-1 to serosal or mucosal sides of flat sheet preparations in Ussing chambers did not change baseline short-circuit current (I(sc)), which served as a marker for chloride secretion. Transmural EFS evoked neurally mediated biphasic increases in I(sc) that had an initial spike like rising phase followed by a sustained plateau-like phase. Blockade of the EFS evoked responses by tetrodotoxin indicated that the responses were neurally mediated. Application of GLP-1 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-1 receptor antagonist exendin-(9-39) suppressed this action of GLP-1. The GLP-1 inhibitory action on EFS-evoked responses persisted in the presence of nicotinic or vasoactive intestinal peptide receptor antagonists but not in the presence of a muscarinic receptor antagonist. GLP-1 significantly reduced EFS-evoked ACh release. In the submucosal plexus, GLP 1R immunoreactivity (IR) was expressed by choline acetyltransferase-IR neurons, neuropeptide Y-IR neurons, somatostatin-IR neurons, and vasoactive intestinal peptide-IR neurons. Our results suggest that GLP-1R is expressed in guinea pig submucosal neurons and that its activation leads to a decrease in neurally evoked chloride secretion by suppressing release of ACh at neuroepithelial junctions in the enteric neural networks that control secretomotor functions. PMID- 22075778 TI - Lipids promote survival, proliferation, and maintenance of differentiation of rat liver sinusoidal endothelial cells in vitro. AB - Primary rat liver sinusoidal endothelial cells (LSEC) are difficult to maintain in a differentiated state in culture for scientific studies or technological applications. Relatively little is known about molecular regulatory processes that affect LSEC differentiation because of this inability to maintain cellular viability and proper phenotypic characteristics for extended times in vitro, given that LSEC typically undergo death and detachment around 48-72 h even when treated with VEGF. We demonstrate that particular lipid supplements added to serum-free, VEGF-containing medium increase primary rat liver LSEC viability and maintain differentiation. Addition of a defined lipid combination, or even oleic acid (OA) alone, promotes LSEC survival beyond 72 h and proliferation to confluency. Moreover, assessment of LSEC cultures for endocytic function, CD32b surface expression, and exhibition of fenestrae showed that these differentiation characteristics were maintained when lipids were included in the medium. With respect to the underlying regulatory pathways, we found lipid supplement-enhanced phosphatidylinositol 3-kinase and MAPK signaling to be critical for ensuring LSEC function in a temporally dependent manner. Inhibition of Akt activity before 72 h prevents growth of SEC, whereas MEK inhibition past 72 h prevents survival and proliferation. Our findings indicate that OA and lipids modulate Akt/PKB signaling early in culture to mediate survival, followed by a switch to a dependence on ERK signaling pathways to maintain viability and induce proliferation after 72 h. We conclude that free fatty acids can support maintenance of liver LSEC cultures in vitro; key regulatory pathways involved include early Akt signaling followed by ERK signaling. PMID- 22075779 TI - Epidermal growth factor/TNF-alpha transactivation modulates epithelial cell proliferation and apoptosis in a mouse model of parenteral nutrition. AB - Epidermal growth factor (EGF) and tumor necrosis factor-alpha (TNF-alpha) signaling are critical for effective proliferative and apoptotic actions; however, little is known about the codependency of these signaling pathways in the intestinal epithelium. Because total parenteral nutrition (TPN) is associated with loss of intestinal epithelial cell (IEC) proliferation and increased apoptosis, we utilized a mouse model to explore these transactivation pathways in small bowel epithelium. Mice underwent intravenous cannulation and were given enteral nutrition or TPN for 7 days. Outcomes included IEC proliferation, apoptosis, and survival. To address transactivation or dependence of EGF and TNF on IEC physiology, TNF-alpha receptor knockout (KO) mice, TNFR1-KO, R2-KO, or R1R2-double KO, were used. Exogenous EGF and pharmacological blockade of ErbB1 were performed in other groups to examine the relevance of the ErB1 pathway. TPN increased IEC TNFR1 and decreased EGF and ErbB1 abundance. Loss of IEC proliferation was prevented by exogenous EGF or blockade of TNFR1. However, EGF action was prevented without effective TNFR2 signaling. Also, blockade of TNFR1 could not prevent loss of IEC proliferation without effective ErbB1 signaling. TPN increased IEC apoptosis and was due to increased TNFR1 signaling. Exogenous EGF or blockade of TNFR1 could prevent increased apoptosis, and both pathways were dependent on effective ErbB1 signaling. Exogenous EGF prevented increased apoptosis in mice lacking TNFR2 signaling. TPN mice had significantly decreased survival vs. controls, and this was associated with the TNFR1 signaling pathway. We concluded that these findings identify critical mechanisms that contribute to TPN-associated mucosal atrophy via altered TNF-alpha/EGF signaling. It emphasizes the importance of both TNFR1 and TNFR2 pathways, as well as the strong interdependence on an intact EGF/ErbB1 pathway. PMID- 22075780 TI - Ni(II) and Pd(II) pyridinyloxazolidine-compounds: synthesis, X-ray characterisation and catalytic activities in the aza-Michael reaction. AB - The 3-phenyl-2-(pyridin-2-yl)oxazolidine ligand (ppo) was synthesised and its coordination behaviour regarding Ni(II) and Pd(II) centres was studied. The reaction with K(2)PdCl(4) affords [Pd(N,N'-ppo)Cl(2)] (1), in which ppo binds to palladium via the pyridyl nitrogen and the oxazolyl nitrogen atoms. On the contrary, reaction with NiCl(2).6H(2)O produces [Ni(N,O-ppo)(2)Cl(2)] (2), in which two ppo ligands are coordinated via the pyridyl nitrogen and the oxygen atom of the oxazolidine ring. The X-ray diffraction analysis of the complexes confirms a square planar geometry for Pd(II) in 1 and an octahedral configuration around Ni(II) in 2, which, to the best of our knowledge, represents the first reported example of a structurally characterised nickel-oxazolidine compound. In addition, both complexes prove to be active catalysts under mild conditions in the aza-Michael reaction of (E)-4-phenylbut-3-en-2-one (benzalacetone) with aliphatic amines. PMID- 22075781 TI - Mechanisms underlying and medical management of L-Dopa-associated motor complications. PMID- 22075782 TI - Colonizing success of saprotrophic and ectomycorrhizal basidiomycetes on islands. AB - The biodiversity of saprotrophic and ectomycorrhizal basidiomycetous macrofungi growing on seven islands in central Japan were compared to examine colonizing success within the context of island biogeography theory. Two hypotheses were tested: that the number of the fungal species depends on island area and that the slope of the species-area curve for saprotrophic and ectomycorrhizal macrofungi differ in response to differences in their nutritional requirements. Data for the number of species that were identified based on sporocarps closely fit the conventional species-area curve. The slopes of the species-area curve for saprotrophic fungi (0.316) and ectomycorrhizal fungi (0.469) were similar to those reported for insects and birds, and plants on other archipelagos, respectively. In addition species-area curve data showed that ectomycorrhizal fungi colonized only islands > 630 m(2). While the species composition of saprotrophic fungi found on any pair of islands was positively correlated to the ratio of the areas of the island pair being compared (smaller/larger), no such relationship was observed for ectomycorrhizal fungi. Conversely similar ectomycorrhizal fungi, mostly those belonging to the genera Amanita, Inocybe, Boletellus and Russula, were found on pairs of islands with similar vegetation in the same geographic region. These results suggested that the colonizing success by ectomycorrhizal fungi is limited by host plant diversity, which is lower on smaller islands, instead of restricted immigration resulting from limited spore dispersal ability. PMID- 22075783 TI - Aquapeziza: a new genus from freshwater and its morphological and phylogenetic relationships to Pezizaceae. AB - An investigation of freshwater fungi on submerged wood in southwestern China led to the discovery of a new discomycete species from a small stream in Yunnan Province. The taxon is characterized morphologically by its combined characters of epigenous, white ascomata, ovoid, amyloid asci and multi-guttulate, single celled, smooth, globose ascospores. Because the taxon cannot be accommodated in any known genus based on morphological characters and molecular data (28S and ITS rDNA sequences) a new genus and species Aquapeziza globispora is proposed to accommodate it. The new genus is circumscribed and a description and illustrations of the new species are provided. Relationships of Aquapeziza in Pezizaceae are inferred from 28S and ITS rDNA sequence analyses. PMID- 22075784 TI - Development of a specific polymerase chain reaction assay for the detection of Basidiobolus. AB - The etiology of chronic diarrhea is complex in humans and animals. It is always necessary to evaluate a list of differential diagnosis, including bacteria, protozoa and fungi. Basidiobolomycosis is a fungal disease reported sporadically worldwide, mainly caused by B. ranarum, a frequent organism found in soil or in the intestine and skin of lizards and frogs. It is an opportunistic pathogen that causes infections characterized by granulomatous lesions in the subcutaneous tissues as well as in the intestinal wall in humans and animals. In this work we have developed a PCR technique to differentiate Basidiobolus from other causes of intestinal disease in dogs and humans. To test the specificity of the PCR assay we included closely related organisms, common intestinal microbiota and pathogenic organisms, such as Aspergillus, Candida, Cryptosporidium, Escherichia, Giardia, Mucor, Proteus, Rhizopus and Salmonella. Pythium insidiosum, which cause clinically similar disease in dogs but require a different treatment. Only Basidiobolus was positive to the PCR assay. PMID- 22075785 TI - The species of Puccinia on Piptocarpha and Vanillosmopsis in the Neotropics. AB - Nine species of Puccinia are known on Piptocarpha and one on closely related Vanillosmopsis. All are mostly from Brazil. Six of the nine Puccinia species on Piptocarpha are proposed as new: Puccinia bipolaris, P. calida, P. douradae, P. macumba, P. manuelensis and P. pipta. Three species are reduced to synonyms of P. piptocarphae: P. leptoderma, P. jahnii, and P. pycnothelis. P. vanillosmopsidis is reduced to a synonym of P. velata on Vanillosmopsis. A key to aid in the identification of the 10 species of Puccinia on Vernonieae is provided. Nomenclature, descriptions, illustrations and notes are presented for each species. PMID- 22075786 TI - Molecular phylogeny of Sydowiellaceae--resolving the position of Cainiella. AB - Cainiella is an ascomycete genus associated with arctic alpine plants. The systematic position of Cainiella has long been unclear, with current classifications placing the genus in either Sordariales or Xylariales. Our molecular results, based on mtSSU, ITS and nLSU rDNA data, clearly show that the genus belongs in the Sydowiellaceae (Diaporthales). The study also includes new sequences of Sydowiellaceae and contributes to a better knowledge of the phylogenetic relationships of that family. PMID- 22075787 TI - Orbilia ultrastructure, character evolution and phylogeny of Pezizomycotina. AB - Molecular phylogenetic analyses indicate that the monophyletic classes Orbiliomycetes and Pezizomycetes are among the earliest diverging branches of Pezizomycotina, the largest subphylum of the Ascomycota. Although Orbiliomycetes is resolved as the most basal lineage in some analyses, molecular support for the node resolving the relationships between the two classes is low and topologies are unstable. We provide ultrastructural evidence to inform the placement of Orbiliomycetes by studying an Orbilia, a member of the only order (Orbiliales) of the class. The truncate ascus apex in the Orbilia is thin-walled except at the margin, and an irregular wall rupture of the apex permits ascospore discharge. Ascus, ascogenous and non-ascogenous hyphae were simple septate, with septal pores plugged by unelaborated electron-dense, non-membranous occlusions. Globose Woronin bodies were located on both sides of the septum. Nuclear division was characterized by the retention of an intact nuclear envelope, and a two-layered disk-shaped spindle pole body. The less differentiated nature of the spore discharge apparatus and septal pore organization supports an earliest diverging position of Orbiliomycetes within the subphylum, while the closed nuclear division and disk-shaped spindle pole body are interpreted as ancestral state characters for Ascomycota. PMID- 22075788 TI - The species of Scleroderma from Argentina, including a new species from the Nothofagus forest. AB - Five ectomycorrhizal species of Scleroderma were identified from herbarium and field-collected specimens from Argentina. A new hypogeous species, Scleroderma patagonicum, was recorded in association with native Nothofagus spp. in Patagonia. The epigeous species S. albidum, S. areolatum, S. bovista and S. citrinum were associated with various exotic tree species. A phylogenetic analysis based on the ITS region of Scleroderma species, including S. patagonicum, illustrates its distinct status within Scleroderma, including its placement among species with reticulate spores. Descriptions with SEM images of the spores and a key to the species are provided. PMID- 22075789 TI - How can we best prevent pertussis in infants? PMID- 22075790 TI - Impact of maternal postpartum tetanus and diphtheria toxoids and acellular pertussis immunization on infant pertussis infection. AB - BACKGROUND: Mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention recommend tetanus and diphtheria toxoids and acellular pertussis (Tdap) vaccine for postpartum women before hospital discharge. In January 2008, this recommendation was implemented in a predominantly Hispanic, medically underserved population at Ben Taub General Hospital (BTGH) in Houston (hereafter the intervention population). METHODS: A cross-sectional study compared preintervention (July 2000 through December 2007) and postintervention (January 2008 through May 2009) periods. Pertussis diagnosis was determined using International Classification of Diseases, Ninth Revision (ICD-9) codes and microbiology reports from 4 major children's hospitals in Houston. Only those infants <=6 months of age with laboratory-confirmed pertussis illness were included. The proportions of pertussis-infected infants born at BTGH in the pre- and postintervention periods were compared. RESULTS: Of 514 infants with pertussis, 378 (73.5%) were identified during preintervention and 136 (26.5%) during postintervention years. These groups were similar in age (mean, 79.3 vs 72 days; P = .08), sex (males, 55% vs 52%; P = .48), length of hospitalization (mean, 9.7 vs 10.7 days; P = .62), mortality (2 deaths each; P = .29) and hospital of pertussis diagnosis. After adjustment for age, sex, and ethnicity, the proportions of pertussis-infected infants born at BTGH and potentially protected through maternal postpartum Tdap immunization were similar for the 2 periods (6.9% vs 8.8%; odds ratio, 1.06; 95% confidence interval, 0.5 2.2; P = .87). CONCLUSIONS: Immunizing only postpartum mothers with Tdap vaccine did not reduce pertussis illness in infants <=6 months of age. Efforts should be directed at immunizing all household and key contacts of newborns with Tdap, not just mothers. PMID- 22075791 TI - Cryptococcus gattii infection in healthy hosts: a sentinel for subclinical immunodeficiency? PMID- 22075792 TI - Prior infections with seasonal influenza A/H1N1 virus reduced the illness severity and epidemic intensity of pandemic H1N1 influenza in healthy adults. AB - BACKGROUND: A new influenza A/H1N1 (pH1N1) virus emerged in April 2009, proceeded to spread worldwide, and was designated as an influenza pandemic. A/H1N1 viruses had circulated in 1918-1957 and 1977-2009 and were in the annual vaccine during 1977-2009. METHODS: Serum antibody to the pH1N1 and seasonal A/H1N1 viruses was measured in 579 healthy adults at enrollment (fall 2009) and after surveillance for illness (spring 2010). Subjects reporting with moderate to severe acute respiratory illness had illness and virus quantitation for 1 week; evaluations for missed illnesses were conducted over holiday periods and at the spring 2010 visit. RESULTS: After excluding 66 subjects who received pH1N1 vaccine, 513 remained. Seventy-seven had reported with moderate to severe illnesses; 31 were infected with pH1N1 virus, and 30 with a rhinovirus. Determining etiology from clinical findings was not possible, but fever and prominent myalgias favored influenza and prominent rhinorrhea favored rhinovirus. Tests of fall and spring antibody indicated pH1N1 infection of 23% had occurred, with the rate decreasing with increasing anti-pH1N1 antibody; a similar pattern was seen for influenza associated illness. A reducing frequency of pH1N1 infections was also seen with increasing antibody to the recent seasonal A/H1N1 virus (A/Brisbane/59/07). Preexisting antibody to pH1N1 virus, responses to a single vaccine dose, a low infection-to-illness ratio, and a short duration of illness and virus shedding among those with influenza indicated presence of considerable preexisting immunity to pH1N1 in the population. CONCLUSIONS: The 2009 A/H1N1 epidemic among healthy adults was relatively mild, most likely because of immunity from prior infections with A/H1N1 viruses. PMID- 22075793 TI - Invasive aspergillosis in children with acquired immunodeficiencies. AB - Invasive aspergillosis has emerged as an important cause of morbidity and mortality in immunocompromised children. It remains difficult to diagnose, and outcome depends on early diagnosis, appropriate treatment, and restoration of host defenses. Pediatric patients represent a unique population in their clinical presentation and epidemiology, particularly in respect to the utility of newer diagnostic tools and the pharmacokinetics of antifungal agents. This article reviews the presentation and epidemiology of invasive aspergillosis in children and adolescents with acquired immunodeficiencies and discusses the value of current diagnostic tools and the options for treatment and prevention in this population. PMID- 22075794 TI - Blastocystis: to treat or not to treat... AB - Parasites in the genus Blastocystis comprise several subtypes (genotypes) and have a worldwide distribution. In some surveys, these are the most common parasites found in human stool specimens. An emerging literature suggests that the pathogenicity of Blastocystis is related to specific subtypes and parasite burden, although even individuals with small numbers of cysts may be symptomatic. Some data suggest an association between infection with Blastocystis and irritable bowel syndrome. However, there are few clinical studies demonstrating a direct relationship between the presence of this parasite and disease, few animal models to explore this relationship, and no consensus as to appropriate treatment. We recommend that asymptomatic individuals with few cysts not be treated. However, those who have gastrointestinal or dermatologic signs and symptoms and many cysts in stool specimens may require treatment. Metronidazole is the drug of choice. Additional studies are required to determine pathogenicity and appropriate therapy. PMID- 22075796 TI - Probing the morphology-device relation of Fe2O3 nanostructures towards photovoltaic and sensing applications. AB - A lot of research on nanomaterials has been carried out in recent years. However, there is still a lack of nanostructures that have a combination of superior properties; both efficient electron transport and high surface area. Here, the authors have tried to develop hybrid alpha-Fe(2)O(3) flower-like morphology which exhibits both superior electron transport and high surface area. Intrigued by the unique properties of Fe(2)O(3) at the nanoscale and its abundance in nature, we have demonstrated a facile template-free solution based synthesis of hybrid alpha Fe(2)O(3) comprising nanopetals nucleating radially from a 3D core. Due to its simplicity, the synthesis process can be easily reproduced and scaled up. We carried out in-depth studies on gas sensing and dye-sensitized solar cell (DSSC) device characterization so as to gain an understanding of how surface area and transport properties are affected by variation in morphology. The hybrid alpha Fe(2)O(3) nanostructures are studied as potential candidates for gas sensors and for the first time as a working electrode for DSSC. PMID- 22075795 TI - Risk factors, clinical features, and outcomes of toxoplasmosis in solid-organ transplant recipients: a matched case-control study. AB - BACKGROUND: Solid-organ transplant (SOT) recipients are considered to be at increased risk for toxoplasmosis. However, risk factors for this infection have not been assessed. The aim of this study was to determine the risk factors, clinical features, and outcomes of toxoplasmosis in SOT recipients. METHODS: A multicenter, matched case-control study (1:2 ratio) was conducted between 2000 and 2009. Control subjects were matched for center, transplant type, and timing. Cases were identified from the hospitals' microbiology and transplantation program databases. Logistic regression was performed to identify independent risk factors. RESULTS: Twenty-two cases (0.14%) of toxoplasmosis were identified among 15 800 SOTs performed in 11 Spanish hospitals, including 12 heart, 6 kidney, and 4 liver recipients. Diagnosis was made by seroconversion (n = 17), histopathologic examination (n = 5), polymerase chain reaction (n = 2), and autopsy (n = 2). In a comparison of case patients with 44 matched control subjects, a negative serostatus prior to transplantation was the only independent risk factor for toxoplasmosis (odds ratio, 15.12 [95% confidence interval, 2.37 96.31]; P = .004). The median time to diagnosis following transplantation was 92 days. Primary infection occurred in 18 (81.8%) cases. Manifestations included pneumonitis (n = 7), myocarditis (n = 5), brain abscesses (n = 5), chorioretinitis (n = 3), lymph node enlargement (n = 2), hepatosplenomegaly (n = 2), and meningitis (n =1). Five patients (22.7%) had disseminated disease. Crude mortality rate was 13.6% (3 of 22 patients). CONCLUSIONS: Although uncommon, toxoplasmosis in SOT patients causes substantial morbidity and mortality. Seronegative recipients are at high risk for developing toxoplasmosis and should be given prophylaxis and receive careful follow-up. PMID- 22075797 TI - Clinical course of grade I-III megaureters detected on prenatal ultrasound. AB - AIM: Primary obstructive megaureter has always been considered a developmental defect. The aim of this study was evaluate the clinical course of grade I-III megaureter at a single Institution through a longitudinal observational study. METHODS: Between April 2004 and April 2006 35 cases of megaureter were observed prenatally. Inclusion criteria were created. Conservative treatment was used for all patients and its efficacy was assessed with routine laboratory tests, ultrasounds and renal scintigraphy. Follow-up was at least three years for all patients. RESULTS: Twenty patients were considered for the study. Single or relapsing infections (36% of patients had more than three urinary tract infections during follow-up) did not seem absolute indications for surgical treatment in these patients, although they are currently the first indication for surgery. CONCLUSION: Clinical results of the study showed that conservative treatment is an effective treatment option. Single or relapsing infections are not a clear indication for surgery. Long-term follow-up for these patients is mandatory. PMID- 22075798 TI - Increased risk of brain injury in IVF babies. AB - AIM: The aim of this paper was to assess brain injury occurrence among in vitro fertilization (IVF) babies. METHODS: We examined all babies born in our hospital in the triennium 2004-2006, comparing the presence of brain injuries between IVF babies and the rest of the population. RESULTS: In IVF group (180 babies), brain injury was present in 4 babies, while in the rest of population (n=3602) it was present in 23 babies (P=0.042, RR: 3.18). IVF babies have a higher risk of being born with a birthweight less than 2 500 grams (P<0.0001; RR: 5.133). When we considered only babies born with a birth weight less than 2 500 grams, the difference of brain injury between the two groups was not significant. CONCLUSION: In IVF babies, brain injury occurred more frequently than in the rest of population. This is probably due to a higher rate of premature births and low birth weight in IVF population. Anyway, this data should be disclosed to future parents to make an informed decision. PMID- 22075799 TI - Evaluation of the diagnostic enigma in Hirschsprung disease. AB - AIM: We aimed to investigate intraoperative diagnosis rate of aganglionosis with hematoxylin eosin (HE) staining, to review the current diagnostic procedures in Hirschsprung disease (HD), to inquire the validity of enzyme staining in diagnosis of HD and to evaluate the utility of ret oncoprotein (RET) antibody for detecting ganglion cells (GC) in paraffin sections. METHODS: Two hundred and thirty three children who are suspected to have HD were included in this study. A total of 302 surgical procedures related to diagnosis and treatment of HD were performed. One to 19 samples (3.5 +/- 2.91) per each case were examined with intraoperative pathological consultation. Although establishing primary diagnoses of HD by frozen sections (FS) examination and performing a one-step approach for treatment have been aimed, consecutive surgical operations were required in 30 cases (12.9%). One hundred and sixty three cases (70%) were male. Seventy eight cases (33.5%) were in neonatal period (mean=13.5 +/- 9.7 days). Only 56 cases were older than 1 year. GC were absent in 137 of cases. Presence of GC with FS examination weren't decided and prior colostomies were performed in 18 cases (7.7%). RESULTS: There were no discrepancies between the FS diagnoses and final diagnoses of the cases except these children. Requisition of consecutive surgical procedures interestingly was lower in neonates than others (P=0.01). Because of long duration, technical difficulty and standardization problems; not only immune histochemical stains but also enzyme stains should not be prefer for demonstration of GC during surgery. CONCLUSION: We suppose that if one-step approach is desired, the intraoperative evaluation of HE staining FS by experienced pathologists is still gold standard in the diagnosis of HD. PMID- 22075800 TI - The incidence of macrophage activation syndrome in children with rheumatic disorders. AB - AIM: Macrophage activation syndrome (MAS) is a rare complication of childhood with rheumatic disease. This syndrome has been reported as a complication of many rheumatic diseases, most commonly in systemic onset of juvenile idiopathic arthritis (SoJIA). The aim of this study was evaluation the rate, symptoms and outcome of MAS in a pediatric rheumatology department in Tehran during 10 years. METHODS: Retrospective review of cases of MAS from the charts of 120 patients with juvenile idiopathic arthritis and systemic lupus erythematosus (SLE). Collected data base of 5 children with MAS from 1998 to 2007, in Children Hospital Medical Center, In Tehran University were collected. RESULTS: Totally 120 patients evaluated in this study including 108 JIA and 12 SLE. Five patients (four girls), and (one boy) were considered to have evidence of MAS. The incidence of MAS in our study was 4.2%. This rate for all JIA patients was 3.7% and for SoJIA, SLE and juvenile idiopaticarthritis (JIA) and polyarticular RF negative JIA was 8.2%, 16.7% and 2.8%, respectively. Mean age of MAS onset was 4.9 years, and duration of rheumatologic disease prior to MAS, 22 months. Four cases (80%) had abnormal liver function during the disease course, and coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four cases (80%). The mortality rate was 40%. CONCLUSION: Although MAS is a rare complication of rheumatologic disorders, because it is potentially fatal it must be thought in each childhood rheumatic disorders with suddenly changes in general condition and decrease peripheral cells. PMID- 22075801 TI - Prevalence of body weight disorders among adolescent school girls in Tarka, Nigeria. AB - AIM: The prevalence of overweight and obesity is increasing worldwide, both in developing and developed countries, and childhood obesity is a serious public health problem. However, there are few studies on prevalence of obesity on Nigerian adolescents in a rural community. Therefore, the aim of this cross sectional study was to determine the prevalence of overweight and obesity among 722 secondary school female students aged 12-18 years living in Wannune, Tarka, Nigeria. METHODS: Participants were selected by purposive sampling from five schools. Anthropometric measurements of height and weight were measured and body mass index (BMI) calculated. The centres for disease control and prevention (CDC) BMI cut-off points were used to generate four BMI categories as follows: BMI <5th percentile, "underweight'; BMI >= 5th to <85th percentile, "normal weight"; BMI >= 85th to <95th percentile, "at-risk-of-overweight"; and BMI >= 95th percentile, "overweight and obese". RESULTS: Findings indicated that 70.1% of the participants had a normal BMI, 7.5% were overweight/obese while 12.5% at risk of overweight and 9.9% were underweight. The levels of obesity, overweight and underweight observed in our sample is quite higher, and indicates overweight and obesity is even occurring in Nigerian adolescents in a rural settings. CONCLUSION: Given that over-nutrition and under-nutrition are noticeable among adolescents' school girls in Tarka, suggests that policy makers and health professionals should design and implement strategies to prevent body weight disorders in children. PMID- 22075802 TI - Sleep and obesity in children: a clinical perspective. AB - Childhood obesity is an international epidemic with many long-term health consequences. The many comorbid conditions associated with obesity underscore the need to explore the different etiologies of obesity which may lead to potential therapeutic interventions. There is growing evidence both that obesity affects sleep, and that sleep patterns and disorders may have an effect on weight. Both respiratory and non-respiratory sleep disorders are associated with obesity; those that have gotten the most attention are the relationships between obesity and obstructive sleep apnea syndrome and short sleep duration. Other forms of sleep-disordered breathing and narcolepsy have also been associated with childhood obesity. Due to the many comorbidities of obesity, this subset of the pediatric population has frequent health care visits across a variety of subspecialties. It is likely that a non-sleep physician will be the first to recognize a sleep-related problem. The aim of this review was to discuss sleep disorders that may be encountered by the general pediatrician and the pediatric subspecialists in their obese pediatric patients and to describe the evidence that links these disorders to obesity. PMID- 22075803 TI - International epidemic of childhood obesity and television viewing. AB - Childhood obesity is one of the most serious global public health challenges of the 21st century. The prevalence of this problem has increased at an alarming rate in many countries. The main causes of childhood obesity are; sedentary lifestyle, unhealthy eating patterns, genetic factors, socio-economic status, race/ethnicity, media and marketing, and the physical environment. Children are clearly being targeted as a receptive market by the manufacturing industry. Undoubtedly, television provides one of the most powerful media through which products can be advertised. Furthermore, food advertising accounted for the largest percentage of these advertisements in virtually all countries. Detailed nutritional analysis of food advertisements identified that up to 90% of food products have a high fat, sugar or salt content. Therefore TV viewing is recently identified as one of the risk factors contributing to development of childhood obesity by several mechanisms. This review provides some facts and figures about the global trend of rising obesity among children, amount and content of television and especially food advertisements being watched by children and its possible mechanisms how to cause adverse effects on children's health and contribute to childhood obesity. PMID- 22075804 TI - Psychosocial aspects of childhood obesity. AB - Rates of childhood obesity are increasing at alarming rates worldwide. This is especially alarming as obesity is associated with many physical and psychological consequences. A great number of studies indicate that obese children have an impaired psychological well-being (e.g., depression, self-esteem, and quality of life) compared to their non-overweight peers. There has been an overwhelming amount of research conducted in this area over the past few decades, and as such, this paper provides a summarized overview of the vast trove of available information on the psychosocial aspects of childhood obesity. In this paper we provide a summarized overview of: 1) psychosocial aspects that contribute to the onset of childhood obesity; 2) psychosocial consequences of childhood obesity; and 3) familial-based lifestyle behavior modification interventions for treating childhood obesity and its treatment success. Although it seems obvious that obese children and adolescents would likely be at higher risk for psychological problems, the mediating factors in the relationship between psychological problems and obesity are still not well established. Obesity is a complex disorder with an equally complex etiology, and is thus associated with complex behaviors and outcomes that make it difficult to study in children. It has been indicated that family-based lifestyle interventions can improve psychological well-being in obese children; however, not all children profit from these interventions. Interventions aimed at improving treatment results need further investigation. For example, interventions targeted specifically at groups that tend to be less successful in weight-loss programs and interventions providing long-term support to these individuals are recommended. PMID- 22075805 TI - Thrombocytosis in children. AB - In healthy pediatric subjects normal count platelet ranges between 250,000 MUL and 450,000 MUL. An elevated platelet count greater than 2 SD defines a condition of thrombocytosis. On a clinical level, thrombocytosis is classified "mild" at a platelet count between >500,000 MUL and <700,000 MUL; "moderate" at a platelet count between >700,000/MUL and <900,000/MUL; "severe" at a platelet count >900,000/MUL; and "extreme" at a platelet count >1,000,000/MUL. Thrombocytosis can be classified as primary or secondary. Primary thrombocytosis is divided into familial and essential. Primary thrombocytosis is an extremely rare clonal disease in childhood with incidence of one per million children, i.e., 60 times lower than in adults. It is classified as a myeloproliferative disorder with polycythemia vera, chronic myeloid leukaemia and myelofibrosis and may be associated with thrombotic or haemorrhagic events. Platelet count is generally above 1,000,000/MUL. The median age at diagnosis is about 11 years. On the contrary, secondary or reactive thrombocytosis (RT) is very common in pediatric age, occurring in 3-13% of hospitalized children because of several causes. Generally, it is a reactive process caused by infection, chronic inflammation, iron deficiency, tissue damage, cancer, drugs and surgical or functional splenectomy. Thrombocytosis is mild in 72-86% of children, moderate in about 6 8%, and extreme in 0.5-3%. Consultation with a pediatric hematologist is required if elevation of platelet count persists, is unexplained or symptomatic. In the majority of cases no treatment is necessary, and the patient must be only closely monitored. PMID- 22075806 TI - [Biography and bibliography of Francesco Fede, the founder of Italian pediatrics]. AB - For the first time, an overall study of the life and works of Francesco Fede, the founder of Italian pediatrics, has been carried out. Unpublished biographical data was collected and the complete bibliographic works of Fede were presented. Fede is the hallmark of both scientific matter, which reached a climax in the definition of the Riga and Fede illness, and for his disinterested dedication as a Member of Parliament to foster development in didactics, research and assistance for pediatrics. PMID- 22075807 TI - [Growth hormone deficiency associated with 22q11.2 deletion: a case report]. AB - The 22q11.2 microdeletion produces many syndromes, characterized by similar phenotypical features. The most known syndromes are: the DiGeorge syndrome, the velocardiofacial syndrome, the conotruncal anomaly face syndrome. The hallmark features are represented by cardiac anomalies, palate defects, immune and cognitive deficiencies, facial dysmorphisms. Less common disorders include: genito-urinary abnormalities, visual defects, autoimmune disorders and pituitary anomalies, being the last represented by growth hormone and/or insulin growth factor-I deficiency. We present the case of a 8 years old male admitted to our Division for failure to thrive. We found growth hormone deficiency and pituitary hypoplasia associated with some of the anomalies shown above, thus we suspected and confirmed the 22q11.2 deletion syndrome. In literature few cases of associated 22q11.2 deletion syndrome with growth hormone deficiency are described, while short stature between children with and children without cleft palate is reported to be more frequent in the first ones, suggesting that the 22q11.2 deletion syndrome remains undetected in many affected children and that the growth hormone deficiency prevalence in affected children has to be investigated. The wide phenotypical presentation of 22q11.2 deletion syndrome requires a multidisciplinary approach to the affected subject and, from the auxologic point of view, is good to monitoring the growing trend and, if short stature is present, check for the growth hormone deficiency. PMID- 22075808 TI - Multi-population QTL detection for aerial morphogenetic traits in the model legume Medicago truncatula. AB - Medicago truncatula, as a model species, is useful to study the genetic control of traits of agronomic interest in legumes species. Aerial morphogenesis is a key component of forage and seed yield. It was measured in four mapping populations originating from five parental lines. Single and multi-population quantitative trait locus (QTL) detections were carried out. A large variation was observed within populations and transgressive segregation was noted. Most traits showed high heritabilities in all seasons. Length of primary branches (LPB, cm) was positively correlated to branch elongation rate (BER, cm day(-1)) and aerial dry matter (ADM, g). Flowering time (FT, degrees C day(-1)) showed negative correlations with length of main stem (LMS, cm) and BER. One hundred and forty one QTLs for BER, LMS, FT, LPB, diameter of primary branches (DPB), number of primary branches (NPB), number of nodes (NI) and ADM were identified and localized over all eight chromosomes. Single and multi-population analyses showed that the most important regions for aerial morphogenetic traits were chromosomes 1, 2, 7 and 8. Multi-population analysis revealed three regions of major QTLs affecting aerial morphogenetic traits (LPB, LMS, NPB, BER and FT). A region involved in flowering time variation was revealed on chromosome 6 on a single population. These results were used to identify candidate genes that could control variation for aerial morphogenesis traits in this species and in related crop legume species. PMID- 22075809 TI - Accuracy of genomic selection in European maize elite breeding populations. AB - Genomic selection is a promising breeding strategy for rapid improvement of complex traits. The objective of our study was to investigate the prediction accuracy of genomic breeding values through cross validation. The study was based on experimental data of six segregating populations from a half-diallel mating design with 788 testcross progenies from an elite maize breeding program. The plants were intensively phenotyped in multi-location field trials and fingerprinted with 960 SNP markers. We used random regression best linear unbiased prediction in combination with fivefold cross validation. The prediction accuracy across populations was higher for grain moisture (0.90) than for grain yield (0.58). The accuracy of genomic selection realized for grain yield corresponds to the precision of phenotyping at unreplicated field trials in 3-4 locations. As for maize up to three generations are feasible per year, selection gain per unit time is high and, consequently, genomic selection holds great promise for maize breeding programs. PMID- 22075810 TI - Towards a repository for standardized medical image and signal case data annotated with ground truth. AB - Validation of medical signal and image processing systems requires quality assured, representative and generally acknowledged databases accompanied by appropriate reference (ground truth) and clinical metadata, which are composed laboriously for each project and are not shared with the scientific community. In our vision, such data will be stored centrally in an open repository. We propose an architecture for a standardized case data and ground truth information repository supporting the evaluation and analysis of computer-aided diagnosis based on (a) the Reference Model for an Open Archival Information System (OAIS) provided by the NASA Consultative Committee for Space Data Systems (ISO 14721:2003), (b) the Dublin Core Metadata Initiative (DCMI) Element Set (ISO 15836:2009), (c) the Open Archive Initiative (OAI) Protocol for Metadata Harvesting, and (d) the Image Retrieval in Medical Applications (IRMA) framework. In our implementation, a portal bunches all of the functionalities that are needed for data submission and retrieval. The complete life cycle of the data (define, create, store, sustain, share, use, and improve) is managed. Sophisticated search tools make it easier to use the datasets, which may be merged from different providers. An integrated history record guarantees reproducibility. A standardized creation report is generated with a permanent digital object identifier. This creation report must be referenced by all of the data users. Peer-reviewed e-publishing of these reports will create a reputation for the data contributors and will form de-facto standards regarding image and signal datasets. Good practice guidelines for validation methodology complement the concept of the case repository. This procedure will increase the comparability of evaluation studies for medical signal and image processing methods and applications. PMID- 22075811 TI - New anatomic division of the orbital and sinus regions: guidance for nasal endoscopic resection of space-occupying lesions. AB - The significance of anatomic divisions of the orbital and sinus regions in providing guidance for nasal endoscopic resection of benign space-occupying lesions was discussed. This retrospective study included 177 cases with benign space-occupying lesions of the orbital and sinus resected between 2001 and 2009. Locations of lesions were assigned to 3 anatomic categories. The 63 cases of benign lesions of the sphenoethmoid-orbital region underwent nasal endoscopic resection. In the 31 cases of benign lesions in the frontoethmoid-orbital region, surgical approaches included nasal endoscopy (n = 15) and combined endoscopic and external (n = 9) and external approaches (n = 4). In 87 cases of lesions in the axillae-ethmoid-orbital region, surgical approaches included nasal endoscopy (n = 67), combined approaches (n = 15), and external approaches (n = 5). Endoscopy facilitated the resection of both 63 cases of benign lesions of sphenoethmoid orbital region, and 82 cases of benign lesions of the frontoethmoid-orbital and maxillae-ethmoid-orbital regions with good prognosis. However, the procedure was relatively more difficult for the other 32 cases of benign lesions of the frontoethmoid-orbital or maxillae-ethmoid-orbital regions. The feasibility of nasal endoscopic resection differs markedly according to anatomic location. Preoperative classification of the site of the lesions will help to define the indications for nasal endoscopic resection of the orbital and sinus regions. PMID- 22075812 TI - Comparison of suture and graft techniques in secondary unilateral cleft rhinoplasty. AB - Every surgeon should master several techniques to modify the nasal tip. For secondary rhinoplasty, various techniques have been described. A modified technique of using the cephalic trim portion of lower lateral cartilage as onlay tip graft is also described. The objective of this single-blind randomized controlled trial was to compare the outcome of suture-only techniques and grafts plus-suture techniques in terms of postoperative tip projection made measurable by the patient as excellent, good, or poor. Sixty patients with cleft nasal tip deformity who gave informed consent were included and randomly assigned to either technique. Patients requiring osteotomies and previously operated on for cleft rhinoplasty were excluded. Postoperative tip projection was assessed by the patient 6 months postoperatively. Mean age was 28.5 +/- 2.1 years in suture technique (group A) and 29.1 +/- 1.9 in suture-plus-graft technique (group B). There were 20 males (66.7%) and 10 females (33.3%) in group A and 22 males (73.3%) and 8 females (26.5%) in group B. Nasal deformity was moderate in 66.7% of cases in group A and 60.0% of cases in group B, whereas nasal deformity was severe in 33.3% of cases in group A and 40% of cases in group B. Postoperative tip projection was excellent in 7 patients (23.3%) in group A and 22 patients (73.3%) in group B, and good in 4 patients (13.3%) in group A and 5 patients (16.7%) in group B, whereas poor results were observed in 19 patients (63.4%) in group A and 3 patients (10.0%) in group B (P = 0.001). Graft-plus-suture technique is an effective method for improving the tip projection. PMID- 22075813 TI - Pattern of odontogenic and nonodontogenic cysts. AB - The jaws are host to a variety of cysts due in large part to the tissues involved in tooth formation. Odontogenic cysts (OCs) are unique in that they affect only the oral and maxillofacial region. There are few studies from sub-Saharan Africa. This study was aimed at describing the pattern of various types of cysts in the oral and maxillofacial region in a Kenyan population. This was done at the Departments of Oral and Maxillofacial Surgery and Oral Medicine and Pathology, University of Nairobi Dental Hospital. This was a retrospective audit. All histopathologic records were retrieved from 1991 to 2010 (19 years) and were counted. The following information was extracted and recorded in a data sheet: age, sex, and the type of cystic lesions. There were 194 cysts (4.56%) diagnosed of 4257 oral and maxillofacial lesions. Of these, 64.4% were from male and 35.6% were from female patients with an age range of 1 to 70 years (mean, 23.76 [SD, 14.05] years; peak and median of 20 years). The most common OCs (57.2%) were dentigerous and radicular, whereas the most common nonodontogenic cyst (42.8%) was nasopalatine duct cyst. Other soft tissue cysts reported were epidermoid, branchial, thyroglossal, dermoid, and cystic hygroma. Oral and maxillofacial cysts are not uncommon in this population, the majority being the OC, dentigerous cyst, followed by the nonodontogenic cyst, nasopalatine cyst. The cysts are male predominant and occur 10 to 15 years earlier compared with those in the white population. PMID- 22075814 TI - Paradoxical herniation in wartime penetrating brain injury with concomitant skull base trauma. AB - A case of the syndrome of the trephined progressing to paradoxical herniation is presented in a patient with a penetrating brain injury, postdecompressive craniectomy, and a delayed cerebral spinal fluid leak from a skull base defect. The patient had a penetrating head trauma from a high-velocity ballistic projectile during military wartime operations. The patient's clinical course, which demonstrates a rare presentation of central sleep apnea syndrome or Ondine's curse, is reviewed. Radiographic imaging includes sequential computed tomography (CT) scans with and without intrathecal contrast. Medical management was directed at increasing the intracranial pressures (ICPs) by placing the patient into Trendelenburg position and increasing hydration. Surgical intervention involved correction of the skull base defect by intranasal endoscopic repair. A literature review of paradoxical herniation and delayed neurologic decline in postcraniectomy patients is conducted, and the surgical and neurocritical care management is discussed. PMID- 22075815 TI - Accessory mandibular condyle at the coronoid process. AB - Coronoid process hyperplasia is a rare cause of mandibular hypomobility. It can result from temporalis muscle hyperactivity, trauma, and neoplasia, but often is idiopathic. Enlargement of the coronoid process leading to pseudojoint formation with the zygomatic arch is known as Jacob's disease. It results most commonly from an osteochondroma of the coronoid process. This is the first reported case of a non-neoplastic accessory mandibular condyle located at the coronoid process articulating with the zygoma. PMID- 22075816 TI - Accurate approach in the treatment of oral bisphosphonate-related jaw osteonecrosis. AB - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is not completely understood and difficult to treat. Even though the occurrence of BRONJ is mainly related to the therapy with intravenous bisphosphonates (BPs), this article reports a case of long-term oral BP use and BRONJ occurrence. In addition, a literature review provides some additional information about BPs, BRONJ, and also a guideline for the prevention and treatment of BRONJ stages. A 79-year-old patient presented intense and persistent pain, purulent secretion, and exposed bone at the right side of the lower jaw. Thus, she was submitted to anamnesis, radiologic and tomographic examinations, and bacterial culture and sensitivity tests. These procedures were followed by surgical debridement of the bone and surrounding tissues/cyst and antibiotic prescription and histopathologic analysis of the fragments. Together, the examinations performed showed the occurrence of stage 2 BRONJ. Moreover, the antibiotic prescription, discontinuation of oral BP, and surgical procedures ensure that the patient had no more symptoms. Therefore, considering the presented case, we believe that an accurate approach is promising to diagnose and treat stage 2 BRONJ and other associated pathologic findings. PMID- 22075817 TI - Oral manifestations of hyperoxaluria. AB - Primary hyperoxaluria is a rare, inherited autosomal recessive disease caused by defects in the metabolism of glyoxylate. Oral manifestations of hyperoxaluria are rare. However, bone and tooth resorption may be the result of chronic inflammation and the presence of osteoclastic cells surrounding the oxalate crystal deposit. A deposit of calcium oxalate in the periodontium was identified in a patient with end-stage renal disease. Dental radiographs indicated bone loss and external tooth resorption. Radiolucent image in the inferior incisor region was observed and removed. The tissue showed granulomatous inflammation with foreign body reaction and associated crystalline deposits. When viewed in polarized light, these deposits are green and presented a birefringent aspect, which were interpreted as calcium oxalate crystals compatible with oxaluria. Oral manifestations of hyperoxaluria are of particular interest because of the unusual location of the oxalate crystal deposition, resulting in aggressive tooth resorption and alveolar bone loss, which may be misdiagnosed. PMID- 22075818 TI - Effects of lidocaine infiltration on cost of rhinoplasty made under general anesthesia. AB - This study aimed to compare the effects of combined and noncombined lidocaine with adrenaline infiltration in general anesthesia (GA) procedures, in which the standard anesthesia depth is monitored by Bispectral Index monitoring, on minimum alveolar concentration (MAC) levels and the costs. Following approval by the local ethics committee, an American Society of Anesthesiologists physical status I-II group of 40 adult patients for whom elective rhinoplasties under GA were planned was divided into 2 double-blind randomized groups. In group 1, GA and lidocaine + adrenaline were administered, whereas in group 2, only GA and adrenaline were administered. All the patients who had been taken to the operation room underwent electrocardiography and measurements of the peripheral oxygen saturation, end-tidal carbon dioxide, heart rate, mean blood pressure, and Bispectral Index monitoring. Using the operation time and the MAC% values, the total consumed inhalation agent amounts were calculated, and the cost difference was determined. The mean blood pressure values were lower in group 1 (P < 0.05). In group 1, the MAC% was 20.83% lower than that of group 2; the consumed desflurane amount was 20.29%, and the cost was 20.29% lower than that of group 2 (P < 0.05). In rhinoplasties under GA, the lidocaine + adrenaline combination infiltration not only decreased inhaled anesthetic requirement and cost but also supported the hemodynamic stability. In addition, surgical satisfaction increased in the lidocaine + adrenaline group because of small number of agitated patients during the recovery period. PMID- 22075819 TI - Evaluation of the sonographic features of metastatic cervical lymph nodes in patients with head and neck malignancy. AB - OBJECTIVES: The aim of the study was to evaluate the sonographic findings of metastatic cervical lymph nodes and of differentiating them from benign ones in patients with head and neck malignancy. METHODS: In this study, the cervical lymph nodes of 14 patients (12 female and 2 male patients; mean age, 52.8 years (with head and neck region malignancy were evaluated ultrasonographically. The gray-scale sonographic parameters, which included short- and long-axis lengths, shape index, presence or absence of hilar echoes and cystic necrosis, parenchymal echogenicity and echo texture, margin, and the color Doppler parameter including vascular pattern were evaluated. Finally, sonographic findings were compared with pathologic results. The following statistical analyses were included: chi(2) test, Fisher exact test, and independent-samples t-test. RESULTS: Overall, 88 cervical lymph nodes were evaluated ultrasonographically. According to the histopathologic results, 77% of them were benign, and 23% were malignant. The study's results showed that the metastatic lymph nodes are accompanied with significantly larger size, rounded shape, absence of hilus, and presence of cystic necrosis and mixed and peripheral vascular pattern. The parameters related to minimal and maximal axis diameter had the highest sensitivity (85%), whereas 2 parameters of vascularity pattern and cystic necrosis had 100% specificity in detecting metastatic cervical lymph nodes. CONCLUSIONS: The results of our study revealed that there was a considerable difference in the diagnostic value of the sonographic parameters, in differentiating metastatic lymph nodes from benign ones, between 4 specific neck regions. PMID- 22075820 TI - "Opposite semilunar" variant of Burow triangle in rotation and advancement flaps. AB - The Burow triangle is an expedient suitably conceived either to facilitate sliding of the flap and avoid folds due to differences in skin distension or to correct coaptation of 2 cutting edges with a different length. In some cases, the triangle cannot be drawn in the right position either because of a particular anatomic site, for example, in proximity to commissures and openings, or because it is contraindicated to avoid unwelcome scar lines. In these cases, a semilunar ablation opposite to the direction of Burow triangle could be a valuable alternative. We report 3 cases where the opposite semilunar variant of Burow triangle was used in critical areas of the face. PMID- 22075821 TI - Nasal lining mobilization for primary and secondary palatoplasty. AB - BACKGROUND: Repair of wide primary cleft palates and secondary cases are challenging. Much literature is dedicated to technique modifications and useful pearls for approaching these patients. Nasal lining is not often highlighted or addressed as a solution to these challenging cleft palate surgeries. The goal of this article was to describe and demonstrate through case examples the simple dissection and significant mobilization of nasal lining as a tool for cleft palate repair. METHODS: Retrospective case examples were selected to highlight the technique. RESULTS AND DISCUSSION: The surgical technique is standardly used by the senior author and has not been previously published. This technique for tension-free nasal lining closure is detailed, and case examples are provided. This technique for nasal lining mobilization is easily reproducible and is versatile. It can be used as an adjunct to any palatoplasty technique and is particularly useful in the treatment of wide clefts and revision cases. PMID- 22075822 TI - Epidemiologic evaluation of mandibular fractures in the Rio de Janeiro high complexity hospital. AB - The aim of this study was to gather data on trauma etiology and mandibular fracture localization in patients who presented at the General Hospital of Nova Iguacu, Rio de Janeiro, Brazil. From March 2007 to December 2008, 95 patients with mandibular fracture were registered in a medical form, at the Bucomaxillofacial Surgery Department of the General Hospital of Nova Iguacu, Rio de Janeiro, Brazil. Concerning mandibular fracture etiology, 21.05% were caused by motorcycle accidents, followed by interpersonal violence without use of weapons (punches, kicks, bumps with the head, blows with the elbow, etc) (16.84%) and interpersonal violence with firearm (14.73%). It was found that 52.63% of the patients had a single fracture line. The most affected fracture area was the parasymphysis (26.02%), followed by the condyle (22.60%) and mandibular angle (18.49%). Concerning the injury area, 24.21% were directed to the mandibular symphysis, 22.17% of the patients did not remember the injury area, and 18.94% had multiple injuries. When the injury was directed to the symphysis, the result was more condyle fractures (11.64%), and injuries at the mandibular angle resulted in fractures at the angle itself (8.90%). The most common fracture cause was traffic accidents, mainly motorcycle accidents, and the most affected areas were the parasymphysis and the condyle. The mandible isolated fractures occurred in half of the cases. Motorcycle accidents resulted in more fractures in the parasymphysis area, and when the symphysis area is affected by injuries, the result is a higher percentage in condyle fractures. PMID- 22075823 TI - Reconstruction of frontal bone using specific implant polyether-ether-ketone. AB - Defects on the craniofacial complex may result in aesthetic defects, functional damage, and psychologic consequences. Previously, surgeons showed no interest in reconstructing the operated area, but in the treatment of the problem, leaving bone contour is a secondary issue. Nowadays, area reconstruction with post reestablishment of contour and local shape has become one of the surgeon's priorities. The use of alloplastic implants with specific digital design has been stated to be an effective technique on the treatment of craniofacial defects, reducing the need for manipulation in the intraoperative period and decreasing surgery time. Polyether ether ketone (PEEK) is a potential candidate because it is a linear polyaromatic semicrystalline polymer that combines strength, stiffness, durability, and resistance. Polyether ether ketone biocompatibility has been supported in literature, and subsequent medical applications of the material have been observed. The aim of this study was to describe a case of frontal bone defect reconstruction in which the PEEK was used as polymer material in a specific implant for the Synthes (PEEK-PSI) patient. PMID- 22075824 TI - Surgical treatment of a giant neurofibroma. AB - Neurofibromatosis type 1, an autosomal dominant inherited disease, presents pathologic symptoms of multiple systems, including neurofibromatosis, skeletal dysplasia, cafe-au-lait spots in skins, and so on. A 45-year-old man with neurofibromatosis type 1 was reported in this article. The patient presented a giant neurofibroma in his head and neck, dysplasia of skull, facial bones and spinal columns, and multiple cafe-au-lait spots in systematic skins. Satisfactory curative effects were obtained in this case after tumor resection and prosthesis implantation. PMID- 22075825 TI - Pitfalls in endoscopic treatment of mandibular subcondylar fractures. AB - OBJECTIVES: The facial trauma surgeon should be able to list indications for endoscopic treatment of mandibular condyle fractures and discuss the limitations and complications of the technique. BACKGROUND: The ideal treatment of mandibular subcondylar fractures continues to be debated. Acceptable results are often obtained with conservative measures such as mandibular maxillary fixation followed by elastics. On the other hand, an open approaches result in potential risk injury to the facial nerve. These 2 arguments have cautioned many surgeons from open treatment of condylar fractures. Recent advances in endoscopic techniques have made the mandibular condyle more accessible with less risk to the facial nerve. As with any new technique, endoscopic treatment of mandibular subcondylar fractures is not without its own limitations and complications. METHODS: This was a retrospective case series. RESULTS: Three patients with mandibular subcondylar fractures with complications following endoscopic treatment were reviewed. There were a total of 4 condylar fractures (1 patient had bilateral fractures). There was 1 incidence of temporary facial nerve paresis, 1 failure of hardware positioning, 1 screw placement into the mandibular foramen, 2 condyles where adequate reduction of the fracture was impossible, and 1 failure to secure a screw into the proximal fracture segment. CONCLUSIONS: Endoscopic management of mandibular subcondylar fractures is a novel treatment with novel types of complications. Although promising, endoscopic treatment of mandibular subcondylar fractures should be approached prudently to avoid potential pitfalls. PMID- 22075826 TI - Open reduction in trapdoor-type blowout fractures using absorbable mesh plates. AB - PURPOSE: In many cases of trapdoor-type orbital blowout fracture, the bony segment has a stable hinge consisting of a greenstick fracture and the sinus mucoperiosteum that is attached to the intact orbital wall. If the displaced bony segment opposite the hinge will be reduced into its original position and will be fixed onto the unaffected bone, the orbital fracture may be reconstructed via the internal fixation of the bony segment itself rather than requiring substitution with an alloplastic implant or a bone graft. METHODS: A retrospective study was conducted from January 2008 to February 2010 in 34 patients with blowout fracture, via retrospective chart review, including detailed preoperative and postoperative evaluations, age, sex, symptoms, and signs, and based on the postoperative complications. The subciliary, transconjunctival, and transcaruncular approaches were used to expose the orbital floor under general anesthesia. The herniated orbital soft tissue was carefully reduced. The displaced bony segment was carefully pulled up and placed in its original anatomic position with a skin hook. A small absorbable mesh plate was inserted between the normal orbital wall and the bony segment, tangential to the edge of the bony defect at the dependent portion. RESULTS: Postoperative examinations such as the traction and forced duction tests showed no eye movement limitation and surgical complications. During the follow-up period, no complications occurred, and the orbital wall was accurately reconstructed in its original anatomic position, as confirmed by postoperative computed tomography scans. CONCLUSIONS: The advantages of internal fixation include anatomic reconstruction of the orbital wall, preservation of the original orbital bone and the mucoperiosteum of the sinus resulting in rapid wound healing and normal mucus drainage function of the sinus, simplicity of the procedure, and the absence of surgery-related complications. This technique is presented as one of the preferred treatments for trapdoor-type orbital blowout fracture. PMID- 22075827 TI - Antral retriever and displaced dental implants in the maxillary sinus. AB - PURPOSE: Removal of antral foreign bodies after implantation is mandatory to avoid infectious processes and may be a troublesome question. Different surgical approaches could be considered, with several limitations and morbidities. METHODS: We present a new tool (Antral Retriever) conceived to remove antral dental implants or any other migrated material through a minimally invasive canine fossa approach, under continuous endoscopic view and local anesthesia. RESULTS AND CONCLUSIONS: Antral Retriever enables the surgeon to successfully remove antral foreign bodies through a canine fossa approach under continuous endoscopic visualization and local anesthesia, with minimal discomfort for the patient PMID- 22075828 TI - Sinusoidal coronal incision. AB - BACKGROUND: The coronal incision is a standard surgical approach in craniofacial surgery. For pediatric patients, it holds a certain risk for unbeneficial aesthetic outcome due to a broadening of the scar in the fast-growing infant skull. METHODS: We readopted the coronal approach over the last decade and developed a sinusoidal type of incision based on the "stealth incision" by Munro and Fearon. We present a calculative standardization of our approach. RESULTS: The sinusoidal coronal approach assures superior aesthetical results with equivalent skeletal exposure. The surgical procedure is simplified and standardized. Even in the fast-growing infant skull, broadening of the scar or vertical divergence is avoided. PMID- 22075829 TI - Severe maxillary atrophy treatment with Le Fort I, allografts, and implant supported prosthetic rehabilitation. AB - PURPOSE: Recently, several authors have described that autologous and fresh frozen bones are effective materials to correct jaw bone defects before endosseous implant positioning. The aim of this study was to report a multistep oral rehabilitation of severe atrophic maxilla by means of Le Fort I osteotomy for maxillary downward and forward repositioning, allografts, implant insertion, and prosthetic loading. METHODS: Patients with severe maxillary atrophy underwent Le Fort I osteotomy associated to fresh-frozen interpositional bone allografts. At 7 months after reconstructive procedure, 2 biopsies for each patient have been taken, and in the same surgical procedure, endosseous implants were placed. Five months afterward, abutments were connected for the final prosthodontic restauration. Each patient was evaluated at 1-year follow-up after prosthetic loading. RESULTS: At 1-year follow-up after functional prosthetic loading, no infection of the allografts or implant failure has been reported. Clinical and radiologic follow-up showed no sign of bone resorption in all the osteotomic sites and in the grafted areas. Histological analysis showed evidence of allograft osteointegration and healing. CONCLUSIONS: Multistep oral rehabilitation of severe atrophic maxilla with Le Fort and interpositional bone allografts represents a reliable surgical technique. According to this clinical, radiologic, and histologic reports, interpositional fresh-frozen bone allograft seems to be a valuable material for grafting jaw as it is cheaper than other materials and is safe, and it avoids donor site, decreasing the morbidity of the treatment PMID- 22075830 TI - Use of various free flaps in progressive hemifacial atrophy. AB - OBJECTIVE: Romberg disease is an uncommon condition manifested by progressive hemifacial atrophy of the skin, soft tissue, and bone. Facial asymmetry with soft tissue deficiency in Romberg disease causes a significant disability affecting the social life and can bring about many psychological problems. METHODS: The aim of surgical treatment is cosmetic amelioration of the defect. Several conventional reconstructive procedures have been used for correcting facial asymmetry. They include fat injections, dermal fat grafts, filler injections, cartilage and bone grafts, and pedicled and free flaps. We report our experiences with 11 patients involving 11 free flaps with a minimum 1-year follow-up. All patients were classified as having moderate to severe atrophy. The average age at disease onset was 4.5 years; the average duration of atrophy was 5.2 years. No patients were operated on with a quiescent interval of less than 1 year. The average age at operation was 20.1 years, ranging from 10 to 55 years. Reconstruction was performed using 4 groin dermofat free flaps, 4 latissimus dorsi muscle free flaps, and 3 other perforator flaps. To achieve the finest symmetrical and aesthetic results, several ancillary procedures were performed in 4 patients. These procedures included Le Fort I leveling osteotomy, sagittal split ramus osteotomy, reduction malarplasty and angle plasty, rib and calvarial bone graft, correction of alopecia, and additional fat graft. RESULTS: All patients were satisfied with the results. CONCLUSIONS: We believe that a free flap transfer is the requisite treatment modality for severe degree of facial asymmetry in Romberg disease. PMID- 22075831 TI - Prospective comparative study of lower lip defects reconstruction with different local flaps. AB - Squamous cell carcinoma is the most common malignancy related to the lips (95%), and the lower lip is more commonly involved. Loss of tissue in the lower lip is treated with a variety of techniques, depending on the extension and location of the defect. This was a prospective case series. In this study, 41 patients with squamous cell carcinoma (30 males, 11 females) who were referred to Razi Hospital of Tehran University of Medical Sciences between 2007 and 2008 and underwent lower-lip reconstruction were included. Defects were divided into 4 groups: less than 30%, between 30% and 50%, between 50% and 80%, and more than 80%. Five different local flaps were used for lower-lip reconstruction. Karapandzic flap was used for 9 patients, double reversed-Abbe flap for 6 patients, Abbe-Estlander and step-ladder flaps for 8 patients, and 10 patients underwent reconstruction operation with reversed-Abbe flap. In comparison to reversed-Abbe flap and step ladder flap, there were no differences functionally and aesthetically except that the step-ladder flap was a single-stage procedure, but the reversed-Abbe flap had 2 stages. There were no functional problems in patients with Estlander flap, but these patients complained of lip asymmetry. There were no functional complaints and aesthetic problems in patients with double reversed-Abbe flap at 3 months after the operation. In patients with 30% to 50% defect of the lower lip, there was no functional and aesthetic difference between Abbe flap and step-ladder flap. Estlander flap is a good choice for reconstruction of lateral or commissural defects of the lower lip. In patients with 50% to 80% defect, it is better to use bilateral reversed-Abbe instead of the Karapandzic flap. PMID- 22075832 TI - Piezosurgery to perform hyoid bone osteotomies in thyroglossal duct cyst surgery. AB - Ultrasonic bone-cutting surgery has been introduced as a feasible alternative to the conventional sharp instruments used in craniomaxillofacial surgery because of its precision and safety. The device used is unique in that the cutting action occurs when the tool is used on mineralized tissues and stops on soft tissues. This work describes the use of piezosurgery for hyoid bone resection in thyroglossal duct cyst surgery, briefly reviews the literature on the surgical technique, and reports our experience with 12 cases. PMID- 22075833 TI - Reconstruction scalp defects after malignant tumor resection with anterolateral thigh flaps. AB - OBJECTIVE: Some patients experience massive neglected scalp malignant tumors involving the soft tissues and bone. Management of these tumors includes thorough tissue resection to obtain negative margins and cover the defects with enough composite tissues. In this article, we presented our experiences of reconstructions with free anterolateral thigh (ALT) flaps. METHODS: We performed a retrospective review of 6 patients who had a single-stage tumor removal and free-tissue transfer over the last 10 years. All the patients were treated with ALT flaps with or without fascia lata according to the defects. RESULTS: The size of the flaps ranged from 8 to 25 cm in length and from 6 to 20 cm in width. All patients healed well without major complications except for 1 case that partial skin-graft loss occurred at the donor sites. CONCLUSIONS: Scalp malignant tumors are generally associated with high mortality rates, and the reconstruction surgery is quite complicated. We demonstrate that free ALT flap transfer yields acceptable survival with favorable safety. PMID- 22075834 TI - Blepharoptosis correction: repositioning the levator aponeurosis. AB - Blepharoplasty remains one of the most popular surgical procedures in Asia. The most common patient complaint leading to a blepharoplasty is limited eye opening causing a narrowing of the palpebral fissure. The typical Asian eye is characterized by puffiness, lack of a supratarsal fold in the upper eyelid, and a narrow palpebral fissure, exhibiting a tired and sleepy appearance. Almost all such patients believe that a simple double-eyelid operation is able to make the eye look bigger with eversion of the eyelashes into a more charming configuration. Some of these patients actually have mild to moderate blepharoptosis, which can present both functional and aesthetic problems. Numerous surgical procedures have been developed to correct ptosis because proper correction can be difficult to achieve. The authors found abnormal lateral deviation of the levator aponeurosis in patients with blepharoptosis and suggest that this abnormality is a major cause of blepharoptosis, particularly in Asians. The authors assessed the effectiveness of a levator aponeurosis medial repositioning technique rather than levator resection or levator plication for mild or moderate ptosis. No disadvantage was attributed to this technique when it was used to correct 87 patients with mild ptosis. Eighty of the 87 patients achieved a good result with the first operation. Undercorrection was observed in 6 patients, and a hematoma was corrected in 1 patient. However, no other major complications related to the technique were encountered. Herein the authors describe their operative technique and present the long-term follow-up results. The authors propose that anatomic repositioning of a laterally deviated levator aponeurosis using the described repositioning technique is highly effective for correcting mild ptosis and can be applied during most surgical blepharoptosis procedures in Asian patients. PMID- 22075835 TI - Successful treatment of large forehead defect after the failure of tissue expansion: changing plan and strategy. AB - Tissue expansion is an effective method in head and neck reconstruction for large defects. Tissue expansion allows enlarged local tissue for advancement or rotation flaps and could result in satisfactory aesthetic and functional outcomes. A 14-year-old boy presented with a 7 * 9-cm(2) traumatic defect on his forehead. We planned a 2-stage operation with tissue expanders. In the first operation, we placed two 100-mL crescent-type tissue expanders supraperiosteally through the scalp hairline incision. After the seventh postoperative day, failure of one of the expanders was found. Hence, we overexpanded the remaining expander using rapid inflation for 7 days (20 mL/d) and changed the plan of the flap design from a bilateral advancement flap to a supratrochlear artery-based unilateral rotational flap. The patient healed uneventfully and had satisfactory results 1 year postoperatively. To overcome tissue expansion failure, an overexpansion technique with multiple small crescent-type expanders was used; a rotational flap based on the supratrochlear artery is a good alternative method. PMID- 22075836 TI - Synchronous lymphomas arising in ipsilateral parotid and submandibular glands: video-assisted surgery. AB - The incidence of lymphomas in salivary glands is 5%, and it represents 10% of malignant salivary tumors. Synchronous tumors arising in different major salivary glands are not only very infrequent but also extremely rare; on the other hand, synchronous lymphomas in ipsilateral major salivary glands have not been reported previously. This article reports a case of synchronous lymphomas in mucosa associated lymphoid tissue in the ipsilateral parotid and submandibular glands. Parotidectomy with facial nerve conservation and resection of the submandibular gland by video-assisted surgery using only a Blair-modified classic incision was performed. One year after the surgical procedure, the patient was followed up at regular intervals, and residual mucosa-associated lymphoid tissue lymphoma did not appear. This case illustrates the importance of the diagnostic possibility of synchronous primary tumors after identification of a simple one; this also reports the video-assisted resection of the submandibular gland using only a Blair incision, when a parotidectomy must be also made. PMID- 22075837 TI - Primary repair of the alveolar cleft. AB - Nasoalveolar fistula and oropharyngeal fistula of the anterior palatal region are very commonly seen in cases when there are concomitant clefts of the lip and the palate. Absence of adequate tissue in that region complicates the treatment and necessitates new tissue transfers from near or distant tissues. Today, the techniques used for correcting cleft lip cannot successfully solve these 2 problems. In this study, we describe a technique that depends on the principle of using the lip mucosal tissues that remains during the Tennison cleft lip correction technique, with a flap designation, to correct the tissue defect of the cleft between the foramen incisivum and lip and the alveolar region. Twenty two patients (13 boys and 9 girls), with ages ranging from 3 to 53 months (mean, 24 mo), with unilateral cleft lip and palate underwent surgery with this new technique. In all these patients, clefts in the anterior palatal and alveolar regions were successfully corrected. Fistula was observed in none of these patients in these regions. Through this method, clefts in the anterior palatal and alveolar regions can be corrected during repair of cleft lips. PMID- 22075838 TI - Nasal tip contouring using lower lateral cartilages. AB - Nasal tip management is the most important and challenging part of rhinoplasty surgery. For nasal tip management, optimal nasal tip projection and rotation must be maintained. For this reason, several methods have been developed to obtain optimal results. In this article, we share with the rhinoplasty surgeons how we use cartilage grafts for nasal tip projection, nasal tip shaping, and maintaining natural and symmetric appearance and avoid "visible cartilage" problem by using a simple and easily applicable method. After performing standard open rhinoplasty techniques, we used the cephalic portion of the lower lateral cartilages to overgraft the already placed numerous layers of shield or onlay grafts. All the cartilage grafts are sutured in their place to prevent malpositions or undesired angularities. We operated on 1480 patients between September of 2002 and September of 2009 for rhinoplasty. Ages of the patients range from 18 to 58 years with nasal tip ptosis. We performed 1235 primary rhinoplasties and 245 secondary rhinoplasties. Of 365 patients, who were followed up regularly, 330 (approximately 90%) were operated on according to this technique and were included in the study. By using such an overgrafting technique for nasal tip, we obtained satisfactory results both by the patients and by the surgeons. Satisfactory results and being a facilitating method for shaping of nasal tip are the advantages of this technique. PMID- 22075839 TI - Uncinectomy through the anterior nasal fontanelle in endoscopic sinus surgery. AB - In functional endoscopic sinus surgery, the resection of the uncinate process is an important step. The traditional method of performing uncinectomy is associated with the risk of penetrating the lamina papyracea and orbital fat exposure. Without timely detection and appropriate treatment, uncinectomy may lead to serious consequences such as blindness. In our study, we used the novel approach of performing uncinectomy through the anterior nasal fontanelle. Orbital complications were observed in 4 of the 112 patients who underwent the traditional method; however, no complication was observed in patients who underwent surgeries with the new approach (P < 0.01). No nasolacrimal duct injury or eye movement disorder was observed in the 2 groups. The percentage of opening of the maxillary sinus ostia by using the new method was significantly greater than that achieved by using the traditional method (97.93% and 70.53%, respectively). The mean score in the visual analog scale, which is used to measure the efficacy of the procedure, for the new method was lower than that for the traditional method, and the difference was statically significant (t = 4.17, P < 0.01). Six and 12 months after the operations, the Lund-Kennedy endoscopy scores obtained when the new method was used were lower than those obtained when the traditional method was used (t = 3.27 and t = 4.40, respectively; P < 0.05). Therefore, uncinectomy through the anterior nasal fontanelle was a convenient and safe procedure and ensured good exposure of the maxillary sinus ostia. This procedure effectively improved the efficacy of endoscopic sinus surgery. PMID- 22075840 TI - Maxillomandibular advancement in obstructive sleep apnea syndrome: a surgical model to investigate reverse face lift. AB - BACKGROUND: The aging process is characterized by multiple signs affecting the upper, the middle, and the lower third of the face; coventionally, face-lift procedures and structural fat grafting are performed to create a younger face. During the life, craniofacial skeleton atrophies, leading to a reduction of the facial height and depth, while increasing the facial width. Maxillomandibular advancement (MMA) by orthognathic surgery restores the lost space dimension, projecting the cheeks, the mouth, and the nose. The aim of this study was to analyze the morphologic change of the face after MMA in patients with obstructive sleep apnea syndrome, focusing on the previously mentioned stigmata of the middle and the lower third of the aging face. METHODS: The records of 16 patients who underwent MMA for obstructive sleep apnea syndrome between January 2005 and December 2008 in the Unit of Maxillofacial Surgery at the Novara Major Hospital were included in this study. We explained to the patients the stigmata of a standard aging face, and we asked them to evaluate each sign affecting the middle and the lower third of their preoperative condition. One positive point was given for the presence of each sign reported by the patients. At 2 years after surgery, we asked the patients to evaluate the previously mentioned aging signs of their postoperative face. Again, 1 positive point was given for the presence of each sign reported by the patients. RESULTS: Although we did not perform statistical evaluation, 13 patients showed a degree of rejuvenation after MMA (the score of the postoperative face is less than the score of the preoperative face). Three patients reported no postoperative change; none reported a more aging face, with a successful "reverse face-lift" occurred in 81% of our cases. CONCLUSIONS: Simultaneous maxillary and mandibular advancements change the skeletal framework of the face, improving soft-tissue support and resulting in rejuvenation of the middle and the lower third of the face. This condition is demonstrated by the results of our study in that all patients appeared postoperatively more youthful from a self-evaluation. PMID- 22075841 TI - Migrated orbital silastic sheet implant mimicking bilateral sinusitis. AB - We present a unique case of a migrated silastic sheet implant that was used during reconstruction of an orbital floor fracture, presenting as bilateral sinusitis. The patient had an orbital floor fracture that was repaired at a local hospital 20 years ago. An orbital silastic sheet implant perforated the bony nasal septum and migrated to the contralateral nasal cavity causing bilateral nasal symptoms. The silastic sheet was successfully removed during endoscopic sinus surgery. Therefore, ocular or nasal symptoms occurring in patients with a previous orbital wall fracture repair must be carefully evaluated clinically and radiologically with a suspicion of late complications, such as migration of the orbital implant. PMID- 22075842 TI - On the nature and signatures of the solvated electron in water. AB - The hydrated electron is one of the simplest chemical transients and has been the subject of intense investigation and speculation since its discovery in 1962 by Hart and Boag. Although extensive kinetic and spectroscopic research on this species has been reported for many decades, its structure, i.e., the dominant electron-water binding motif, and its binding energy remained uncertain. A recent milestone in the research on the hydrated electron was the determination of its binding energy by liquid-jet photoelectron spectroscopy. It turned out that the assumption of a single electron binding motif in liquid water is an oversimplification. In addition to different isomers in cluster spectroscopy and different transient species of unknown structure in ultrafast experiments, long lived hydrated electrons near the surface of liquid water have recently been discovered. The present article gives an account of recent work on the topic "solvated electrons" from the perspectives of cluster spectroscopy, condensed phase spectroscopy, as well as theory. It highlights and critically discusses recent findings and their implications for our understanding of electron solvation in aqueous environments. PMID- 22075843 TI - Porphyrin-functionalised rotaxanes for anion recognition. AB - The synthesis and anion-recognition properties of two new porphyrin functionalised [2]rotaxane host molecules are described. The rotaxane compounds are prepared via a chloride-anion-templated clipping strategy. (1)H NMR titration experiments demonstrate that the rotaxane host systems exhibit high binding affinities and general selectivities for chloride anions in DMSO-d(6) or CDCl(3)/CD(3)OD solvent systems. UV-visible and fluorescence spectroscopy experiments reveal that the rotaxane receptors are ineffective as optical anion sensors. However, both receptors are shown to be capable of detecting chloride anions electrochemically via cathodic shifts in the porphyrin P/P(+) redox couples. PMID- 22075844 TI - Diluted povidone-iodine inhibits tumor growth through apoptosis-induction and suppression of SOD activity. AB - Povidone-iodine (PVP-I) is widely used in clinical practice as an antiseptic and flushing agent after surgery to remove a tumor. Our present study was designed to determine whether diluted PVP-I is cytotoxic to colon cancer cells and ascetic tumor cells in vitro and to examine its antitumor effects in vivo. In vitro, CT26 and H22 cells treated with different concentrations of diluted PVP-I (0-1.56 ug/ml) were analyzed using the mononuclear cell direct cytotoxicity assay (MTT) and a flow cytometry assay. In vivo, Balb/c mice injected in the abdominal cavity with CT26 cells or H22 cells were treated intraperitoneally with different concentrations of PVP-I (0-312.5 ug/mouse), cisplatin (40 mg/kg) or 5'-FU (30 mg/kg) or left untreated. In vitro, the studies demonstrated the antiproliferative and significant apoptosis-inducing effects of PVP-I in a dose- and time-dependent manner. In vivo, PVP-I significantly repressed the growth of H22 and CT26 cells in Balb/c mice compared to controls. To explore the mechanism of the antitumor effect of PVP-I, the superoxide dismutase (SOD) activity of ascites extracted from a mouse model and the supernatant of CT26 cells was detected by an SOD kit. The activity of SOD was significantly inhibited in the experimental groups. Taken together, our data suggest that PVP-I exhibits a strong inhibitory effect on tumor growth in colon cancer (CT26) and hepatoma (H22) resulting from apoptosis, both in vitro and in vivo, suggesting a new potential therapeutic approach after tumor excision surgery to colon cancer and hepatoma. PMID- 22075845 TI - Expression of paxillin and FAK mRNA and the related clinical significance in esophageal carcinoma. AB - The objective of the present study was to investigate the expression of paxillin and focal adhesion kinase (FAK) mRNA in esophageal carcinoma tissues, and their relationship with clinicopathological parameters, as well as to analyze the correlation of paxillin and FAK mRNA levels in esophageal carcinoma. By using reverse transcription polymerase chain reaction (RT-PCR), the mRNA expression levels of paxillin and FAK were detected in 121 samples of esophageal carcinoma, 43 samples of atypical hyperplasia and 56 samples of normal esophageal mucosa. The results showed that the positive rates of paxillin and FAK mRNA expression in esophageal carcinoma were 87.6 and 80.17%, respectively, which were significantly higher (P<0.05) than those in atypical hyperplasia (44.19 and 39.53%) and normal esophageal mucosa (5.36 and 12.5%). Notably, paxillin and FAK mRNA expression levels were significantly correlated with the differentiation degree and depth of invasion of esophageal carcinoma and with lymph node metastasis (P<0.05). In addition, paxillin and FAK mRNA expression levels in esophageal carcinoma were positively correlated (r=0.4804, P=0.000). In conclusion, the combined detection of paxillin and FAK mRNA expression is expected to provide a theoretical basis for the molecular diagnosis of esophageal carcinoma. PMID- 22075846 TI - Reorganization of perylene bisimide J-aggregates: from delocalized collective to localized individual excitations. AB - Water-induced reorganization of individual one-dimensional J-aggregates of perylene bisimide (PBI) dyes was observed by fluorescence microscopy. Fluorescence spectra and decay kinetics of individual J-aggregates immobilized on glass surfaces were measured under a dry nitrogen atmosphere and under humid conditions. The fluorescence properties of PBI J-aggregates arisen from collective excitons under dry nitrogen atmosphere were changed to those of non interacting dye monomers when water vapor was introduced into the environment (sample chamber). Time-dependent changes of the fluorescence spectra and lifetimes upon exposure to water vapor suggest an initial coordination of water molecules at defect sites leading to the formation of H-type dimer units that act as exciton quenchers, and a subsequent slower disintegration of the hydrogen bonded J-aggregate into monomers that lack resonance coupling. Our present studies resulted in a direct demonstration of how drastically the optical properties of molecular ensembles and characteristics of their excited states can be changed by delicate reorganization of dye molecules at nanometre scales. PMID- 22075847 TI - Molecular biomarker of inflammatory response is associated with rebleeding in spontaneous intracerebral hemorrhage. AB - BACKGROUND AND PURPOSE: Rebleeding in spontaneous intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality among stroke survivors. Due to the links between inflammation and rebleeding, we hypothesized that the biomarkers of inflammation are associated with the pathogenesis of rebleeding in ICH. We sought to investigate whether these biomarkers and clinical variables on admission can provide prognostic information on the risk of rebleeding. METHODS: This prospective study enrolled 59 consecutive patients with spontaneous ICH. We determined the concentrations of interleukin-10 (IL-10), intercellular adhesion molecule-1, and complement 3 in blood samples obtained on admission. RESULTS: Univariate analysis indicated that hematoma volume, leukocyte count, hydrocephalus, and plasma IL-10 levels were associated with rebleeding. Multivariate logistic regression analysis indicated that hydrocephalus (95% CI of OR, 1.6-26.7) and IL-10 (95% CI of OR, 1.03-1.22) were independently associated with an increased probability of rebleeding. CONCLUSION: These data suggest that IL-10, a molecular biomarker of inflammatory response in the early acute phase of ICH, is associated with subsequent rebleeding. PMID- 22075848 TI - Prognostic significance of Tiam1 expression in papillary thyroid carcinoma. AB - T lymphoma and metastasis gene 1 (Tiam1) is a guanine nucleotide exchange factor (GNEF) that regulates the guanosine triphosphatase to facilitate the exchange of guanosine diphosphate for guanosine triphosphate. It specifically activates Rac1, a member of the Rho family of GTPases. Tiam1 is involved in cell proliferation, cytoskeletal organization, cellular adhesion, and transcriptional activation. It has been suggested that alterations in Tiam1 expression might contribute to the progression of various human cancers. The usefulness of Tiam1 expression as a prognostic marker in papillary thyroid carcinoma (PTC) has not been investigated yet. The aim of this study was to analyze the expression of Tiam1 in PTC as well as its association with the clinicopathologic features and prognostic significance. Surgical tissue samples were taken from 106 PTC patients who had been followed up for at least 9.3 years. Strong expression of Tiam1 was detected in 54% of the cases. Tiam1 expression was associated significantly with various clinicopathologic parameters, such as gender (P=0.039), tumor multicentricity (P=0.0124), histologic subtype (P=0.0427), TNM stage (P=0.0151), and distant metastases at diagnosis (P=0.0001). Survival analysis showed that the Tiam1 low expression group had a significantly shorter overall survival time than Tiam1 high-expression group (P=0.0007). Multivariate analysis showed that Tiam1 expression was a significant and independent prognostic indicator (P=0.0090) for PTC patients. Tiam1 expression may be a novel and independent prognostic marker of PTC patients. PMID- 22075849 TI - Xenogeneic chondrocytes promote stable subcutaneous chondrogenesis of bone marrow derived stromal cells. AB - The local microenvironment may change the ultimate fate of engineered cartilage differentiated from bone marrow stromal cells (BMSCs) after subcutaneous implantation. Chondrogenically differentiated BMSCs directed by growth factors or low-intensity ultrasound are apt to fibrose or vascularize in the subcutaneous environment, while BMSCs implanted in articular cartilage defects can form stable cartilage. We hypothesized that chondrocytes would provide an ideal chondrogenic environment, and thus promote the maintenance of the chondrocytic phenotype in ectopia. To test this hypothesis, we developed a new method to promote chondrocyte development from BMSCs in a chondrogenic environment produced by xenogeneic chondrocytes and compared the subcutaneous chondrogenesis of BMSCs mediated by xenogeneic chondrocytes with that produced by growth factors. These results indicate that subcutaneous chondrogenesis of BMSCs directed by xenogeneic chondrocytes is more effective than that induced by growth factors. BMSCs induced by xenogeneic chondrocytes formed relatively mature cartilage before or after implantation, following 4 weeks of culture, which reduced the induction time in vitro and led to maintenance of a stable cartilage phenotype after subcutaneous implantation. PMID- 22075850 TI - Abstraction of beta-hydrogen vs. alkyl groups in reactions of dialkylzinc compounds and bis(oxazolinyl)borane. AB - An ambiphilic bis(oxazolinyl)borane proligand and zinc dialkyls react via alkyl group transfer or beta-hydrogen abstraction. The latter process is favored by formation of a bis(oxazolinyl)borane-zinc adduct that positions a beta-hydrogen in the proximity of the Lewis acid center. PMID- 22075851 TI - Diabetes care among Somali immigrants and refugees. AB - The risk for development of diabetes and associated complications among immigrants increases in the years after arrival to the United States. Somali immigrants and refugees represent the largest subset of African immigrants to the United States, yet little is known about the quality of their diabetes care. Therefore, adherence with diabetes quality indicators (Hemoglobin A1C <7%, LDL cholesterol <100 mg/dl, blood pressure <130/80 mm Hg) were compared between Somali and non-Somali patients with diabetes at a large academic primary care practice in the United States in 2008. Demographic and health-seeking behavior variables were assessed for association with adherence among the Somali population. A total of 5,843 non-Somali and 81 Somali patients with diabetes were identified. Somali patients with diabetes were less likely to meet the criteria for optimal glycemic control than non-Somali patients (40.6% vs. 53.9%; P=0.02). There was a similar, though statistically non-significant, trend towards lower rates of lipid control among Somali patients. There was no difference in achievement of optimal blood pressure between the two groups. There was a strong association between number of primary care visits during the study interval and achievement of all three diabetes care quality goals. This study demonstrates disparities in achievement of diabetes management quality goals among Somali patients compared with non-Somali patients, highlighting the need for additional system and practice changes to target this particularly vulnerable population. PMID- 22075852 TI - Cancer screening behaviors among Latina women: the role of the Latino male. AB - The purpose of this article is to determine, through a community-based breast and cervical cancer intervention program, the impact Latino males may have on Latinas and their cancer screening behaviors. This report includes data collected from 163 Latino males recruited throughout rural Arkansas and four New York City boroughs for the Esperanza y Vida program, designed to evaluate cancer screening outcomes among Latinas and address their health care needs and cancer control challenges. Basic demographics and identical pre- and post-program knowledge surveys were collected and analyzed using SPSS 15.0 and SAS 9.2. Results from this study suggest Latino men have little knowledge about breast or cervical cancer screening and are unfamiliar with their partners' screening histories. Male participants were also less likely to complete program assessment forms (pre, post, demographic questionnaires) and more likely to commit response errors (i.e. multiple answers, illegible responses). These findings suggest that including males in education programs for Latinas may be a crucial component in decreasing cancers among this segment of the population. The further development of programs such as Esperanza y Vida, that empowers Latino males, will be important in reducing the unequal burden of breast and cervical cancers for Latinas. It is important to continue including Latino men in these types of studies because the impact of their role on Latina's health remains understudied, unknown, and misunderstood. PMID- 22075853 TI - Jaundice due to suspected statin hepatotoxicity: a case series. AB - Statin drugs are widely used worldwide and are generally considered safe and well tolerated. Only small proportion of patients receiving statins develop elevations of liver enzymes and an even smaller proportion will have clinically significant hepatitis induced by statins. We describe four patients with jaundice caused by drug-induced liver injury, where the most likely agent was a statin drug, over a period of approximately three year in Iceland. We calculate the risk of jaundice caused by statin drugs, from sale in the whole country of Iceland, to be one in 17,434 users a year. This is a higher risk than has previously been estimated and we challenge the current opinion that statins rarely cause clinically significant drug-induced liver injury and encourage alertness when managing patients with statins with regard to clinical signs of hepatitis before jaundice occurs. PMID- 22075854 TI - Serum antibodies and anthropometric data at diagnosis in pediatric Crohn's disease. AB - BACKGROUND: Serum antibodies, including ASCA, anti-OmpC, and ANCA, correlate with disease location and predict disease phenotype in inflammatory bowel disease. AIM: The objective of this study was to determine relationships between serum antibody status and anthropometric data for children with newly diagnosed Crohn's disease. METHODS: A retrospective review was conducted on children diagnosed with Crohn's disease at our institution from 2003 to 2008. Patients who had ASCA IgA, ASCA IgG, anti-OmpC, and pANCA antibodies, and anthropometric data measured before diagnosis and therapy were included. Z-scores for height and weight were compared among groups according to the presence of specific antibodies. Spearman's rank correlation was used to assess association between antibodies and growth data. RESULTS: One hundred and two patients, mean age 11.9 years, met the inclusion criteria. Patients with the presence of any of the four antibodies had lower mean height and weight z-scores than patients without any antibodies present. When individual antibodies were studied, patients with positive ASCA titers had lower mean weight and height z-scores than patients without any antibodies present. Spearman's rank correlation coefficient demonstrated a significant association between increasing ASCA titers and lower weight z-scores, but not lower height z-scores. CONCLUSIONS: Pediatric patients with newly diagnosed Crohn's disease and the presence of ASCA antibodies have lower mean height and weight z-scores. This study provides evidence that specific subsets of children with Crohn's disease may be at greater risk of growth impairment. PMID- 22075855 TI - Diversity and distribution of avian haematozoan parasites in the western Indian Ocean region: a molecular survey. AB - The genetic diversity of haematozoan parasites in island avifauna has only recently begun to be explored, despite the potential insight that these data can provide into the history of association between hosts and parasites and the possible threat posed to island endemics. We used mitochondrial DNA sequencing to characterize the diversity of 2 genera of vector-mediated parasites (Plasmodium and Haemoproteus) in avian blood samples from the western Indian Ocean region and explored their relationship with parasites from continental Africa. We detected infections in 68 out of 150 (45.3%) individuals and cytochrome b sequences identified 9 genetically distinct lineages of Plasmodium spp. and 7 lineages of Haemoproteus spp. We found considerable heterogeneity in parasite lineage composition across islands, although limited sampling may, in part, be responsible for perceived differences. Two lineages of Plasmodium spp. and 2 lineages of Haemoproteus spp. were shared by hosts in the Indian Ocean and also on mainland Africa, suggesting that these lineages may have arrived relatively recently. Polyphyly of island parasites indicated that these parasites were unlikely to constitute an endemic radiation and instead probably represent multiple colonization events. This study represents the first molecular survey of vector-mediated parasites in the western Indian Ocean, and has uncovered a diversity of parasites. Full understanding of parasite community composition and possible threats to endemic avian hosts will require comprehensive surveys across the avifauna of this region. PMID- 22075856 TI - Not just for Christmas. PMID- 22075857 TI - Private medical notes. PMID- 22075858 TI - Forward to harmonisation. PMID- 22075859 TI - Denture record. PMID- 22075860 TI - Unfortunate comments. PMID- 22075861 TI - Proportional to the investment. PMID- 22075862 TI - Cultural preparations. PMID- 22075863 TI - Time for change? PMID- 22075864 TI - Vegetable granuloma. PMID- 22075865 TI - NHS amazement. PMID- 22075880 TI - Adult dental health surveys: 40 years on. AB - A comparison of the results of the Adult Dental Health Surveys in England and Wales in 1968 and England, Wales and Northern Ireland in 2009 shows marked improvements in many aspects of oral health. Edentulousness in adults aged 16 years and over has reduced from 37% to 6%. Dentate adults today have 9 to 10 more sound teeth in all age groups up to 44 years, than was the case 40 years ago. The number of decayed or unsound teeth has halved in every age group between 1968 and 2009. PMID- 22075881 TI - Soft tissue manipulation for single implant restorations. AB - Achievement of optimal aesthetics on implants in the anterior region can be difficult due to inherent differences to the natural dentition. An important consideration is the peri-implant soft tissues which can be modified to create a more natural emergence profile and contour. The methods with which this can be achieved vary as can methods for recording soft tissue changes and relaying this to technician colleagues. This review appraises some techniques available for the manipulation of the soft tissue profile on single implant restorations. PMID- 22075882 TI - Relative efficacy of oral analgesics after third molar extraction--a 2011 update. AB - This article provides a summary of the efficacy, and relative efficacy, of 38 different drugs or drug combinations tested in standard postoperative pain trials. It will help clinicians and patients make informed choices about analgesia based on pain relief, duration of action, and adverse events, which can then be put into context for the individual patient, depending on local availability. This article highlights the fact that no single drug is effective in all patients--even the best drugs fail to provide good levels of pain relief in at least 30%. These patients should try a different analgesic. PMID- 22075887 TI - Summary of: Is there a differential in the dental health of new recruits to the British Armed Forces? A pilot study. PMID- 22075888 TI - Summary of: Pharmacy counter assistants and oral health promotion: an exploratory study. PMID- 22075905 TI - Hard times can happen to anyone--even a dentist. AB - The BDA Benevolent Fund has been helping needy dentists and their families for 130 years, while the Dentist Health Support Trust, founded in 1986, offers support specifically on addiction and other mental health issues. The Ben Fund offers a lifeline to those struggling with poverty arising from illness, accidents, bereavement, addiction, mental health issues, and many other difficulties. It may be that someone needs financial help to deal with a short term problem before they get themselves back on track, and the Fund can do this with a one-off grant or perhaps an interest-free loan, to be repaid when their life is on an even keel again. Other people may face long-term uncertainty and need regular support. PMID- 22075911 TI - Is there a differential in the dental health of new recruits to the British Armed Forces? A pilot study. AB - BACKGROUND AND AIM: Figures from the British Defence Dental Services reveal that serving personnel in the British Army have a persistently lower level of dental fitness than those in the Royal Navy or the Royal Air Force. No research had been undertaken to ascertain if this reflects the oral health of recruits joining each Service. This study aimed to pilot a process for collecting dental and sociodemographic data from new recruits to each Service and examine the null hypothesis that no differences in dental health existed. METHOD: Diagnostic criteria were developed, a sample size calculated and data collected at the initial training establishments of each Service. RESULTS: Data for 432 participants were entered into the analysis. Recruits in the Army sample had a significantly greater prevalence of dental decay and greater treatment resource need than either of the other two Services. Army recruits had a mean number of 2.59 (2.08, 3.09) decayed teeth per recruit, compared to 1.93 (1.49, 2.39 p <0.01) in Royal Navy recruits and 1.26 (0.98, 1.53 p <0.001) in Royal Air Force recruits. Among Army recruits 62.7% were from the two most deprived quintiles of the Index of Multiple Deprivation compared to 42.5% of Royal Naval recruits and 36.6% of Royal Air Force recruits. CONCLUSION: A significant difference in dental health between recruits to each Service does exist and is a likely to be a reflection of the sociodemographic background from which they are drawn. PMID- 22075912 TI - Pharmacy counter assistants and oral health promotion: an exploratory study. AB - BACKGROUND: The involvement of community pharmacists in oral health promotion is being increasingly recognised and studied. However, a large proportion of interactions in community pharmacies take place with pharmacy counter assistants rather than the pharmacist, and the role of pharmacy counter assistants in oral health promotion has received little or no attention until now. AIMS: To clarify the current state of affairs on pharmacy counter assistants' involvement with oral health promotion. DESIGN AND METHODS: A postal-questionnaire-based survey of pharmacy counter assistants across East Yorkshire, North Lincolnshire and the Doncaster area. One hundred addresses were included and 35 responses were received. RESULTS: Pharmacy counter assistants are infrequently approached by the public for advice on matters of oral health and advice is not often volunteered despite a reasonable knowledge of the subject. Respondents identified a role for themselves in educating patients/customers, which they are keen to expand. CONCLUSIONS: The expansion of the pharmacy counter assistant's role in oral health promotion would be of value to patients/customers. This should include increased opportunistic education and a more integrated position of pharmacy within a holistic health promotion strategy. PMID- 22075913 TI - [Associations between workplace bullying, harassment, and stress reactions of professional caregivers at welfare facilities for the elderly in Japan]. AB - OBJECTIVE: The purpose of this study was to describe workplace bullying experienced by professional caregivers at welfare facilities for the elderly in Japan and to confirm its effects on stress reactions. METHODS: A cross-sectional survey was carried out using self-administered questionnaires in 2009 of all the employees working in rural area of facilities for long-term care. Among the 1,233 respondents who filled out all questionnaires concerning stress reactions the Japanese version of the Negative Acts Questionnaire (NAQ) (response rate: 63.9%), we analyzed 897 professional caregivers. We measured stress reactions by using the stress reaction scores of the Brief Job Stress Questionnaire (29 items) and workplace bullying and harassment by using NAQ. We used the unpaired t-test and analysis of covariance (ANCOVA) to compare crude and adjusted average stress reactions with groups classified on the basis of each subscale of the NAQ or all of them. RESULTS: About 40% of both men and women suffered from "malicious gossip" and over 60% of both men and women experienced "someone withholding necessary information so that their work gets complicated". Among women, scores of the lack of vigor and fatigue were significantly higher in caregivers targeted by person-related bullying than those not targeted (p<0.05). Scores of depression were significantly higher in caregivers targeted by work-related bullying than those not targeted (p<0.05). Scores of anxiety were significantly higher among caregivers targeted by sexual harassment than those not targeted (p<0.05). Among men, scores of the lack of vigor were significantly lower in caregivers targeted by work-related bullying than those not targeted (p<0.05). CONCLUSIONS: Among women, workplace bullying or harassment could may aggravate effects on psychological stress responses. While among men, work-related bullying was positively associated with vigor. PMID- 22075914 TI - [Mental health of workers and the effects of behavioral traits -validation of causal model using covariance structure analysis-]. AB - PURPOSE: To clarify the mental health factors of workers and to verify the causal correlation between their behavioral traits and mental health. METHOD: We asked 1,425 subjects working at private enterprises and local government offices, as well as members of labor unions, to anonymously respond to questionnaires. RESULT: We examined the causal influence of workers' behavioral traits on negative mental health by covariance structure analysis. Workers'other-reward oriented self-image variables indicated by behavioral traits, such as self repression and interpersonal dependency, directly affected negative mental health. Workers'perceived emotional support indirectly affects their mental health through self-image variables and perceived stressors. Additionally, simultaneous multi-population analysis verified that different populations did not show differences, and maintained the same structure. DISCUSSION: Other-reward oriented self-image directly affected negative mental health, and its impact was the largest. Therefore, to prevent negative mental health, the results indicate that it is important to shift self-image to a self-reward oriented one. Additionally, the results indicate the need for effort to perceive emotional support at the workplace and heighten the ability of self-expression and feelings of self-esteem. This can encourage changing to a self-reward oriented self-image and a preventive effect is expected. PMID- 22075915 TI - The functional and molecular characterisation of human embryonic stem cell derived insulin-positive cells compared with adult pancreatic beta cells. AB - AIMS/HYPOTHESIS: Using a novel directed differentiation protocol, we recently generated up to 25% insulin-producing cells from human embryonic stem cells (hESCs) (insulin(+) cells). At this juncture, it was important to functionally and molecularly characterise these hESC-derived insulin(+) cells and identify key differences and similarities between them and primary beta cells. METHODS: We used a new reporter hESC line with green fluorescent protein (GFP) cDNA targeted to the INS locus by homologous recombination (INS (GFP/w)) and an untargeted hESC line (HES2). INS (GFP/w) allowed efficient identification and purification of GFP producing (INS:GFP(+)) cells. Insulin(+) cells were examined for key features of adult beta cells using microarray, quantitative PCR, secretion assays, imaging and electrophysiology. RESULTS: Immunofluorescent staining showed complete co localisation of insulin with GFP; however, cells were often multihormonal, many with granules containing insulin and glucagon. Electrophysiological recordings revealed variable K(ATP) and voltage-gated Ca(2+) channel activity, and reduced glucose-induced cytosolic Ca(2+) uptake. This translated into defective glucose stimulated insulin secretion but, intriguingly, appropriate glucagon responses. Gene profiling revealed differences in global gene expression between INS:GFP(+) cells and adult human islets; however, INS:GFP(+) cells had remarkably similar expression of endocrine-lineage transcription factors and genes involved in glucose sensing and exocytosis. CONCLUSIONS/INTERPRETATION: INS:GFP(+) cells can be purified from differentiated hESCs, providing a superior source of insulin producing cells. Genomic analyses revealed that INS:GFP(+) cells collectively resemble immature endocrine cells. However, insulin(+) cells were heterogeneous, a fact that translated into important functional differences within this population. The information gained from this study may now be used to generate new iterations of functioning beta cells that can be purified for transplant. PMID- 22075916 TI - Autophagy deficiency in beta cells leads to compromised unfolded protein response and progression from obesity to diabetes in mice. AB - AIMS/HYPOTHESIS: The unfolded protein response (UPR) in endoplasmic reticulum (ER) and autophagy are known to be related. We investigated the role of autophagy in UPR of pancreatic beta cells and the susceptibility of autophagy-deficient beta cells to the ER stress that is implicated in the development of diabetes. METHODS: Rat insulin promoter (RIP)-Cre(+);autophagy-related 7 (Atg7)(F/W) mice were bred with ob/w mice to derive RIP-Cre(+);Atg7(F/F)-ob/ob mice and to induce ER stress in vivo. GFP-LC3(+)-ob/ob mice were generated to examine in vivo autophagic activity. Real-time RT-PCR was performed to study the expression of the genes of the UPR machinery. Proteolysis was assessed by determining release of incorporated radioactive leucine. RESULTS: Production of UPR machinery was reduced in autophagy-deficient beta cells, which was associated with diminished production of p85alpha and p85beta regulatory subunits of phosphoinositide 3 kinase. Because of compromised UPR machinery, autophagy-deficient beta cells were susceptible to ER stressors in vitro. When mice with beta cell-specific autophagy deficiency, which have mild hyperglycaemia, were bred with ob/ob mice to induce ER stress in vivo, severe diabetes developed, which was accompanied by an increase in beta cell death and accumulation of reactive oxygen species. The increased demand for UPR present in obesity was unmet in autophagy-deficient beta cells. Autophagy level and autophagic activity were enhanced by lipid, while proteolysis was reduced. CONCLUSIONS/INTERPRETATION: These results suggest that autophagy is important for intact UPR machinery and appropriate UPR in response to lipid injury that increases demand for UPR. Autophagy deficiency in pancreatic beta cells may contribute to the progression from obesity to diabetes. PMID- 22075917 TI - New Iranian and Australian peach latent mosaic viroid variants and evidence for rapid sequence evolution. AB - Peach latent mosaic viroid isolates from peach and plum in Iran have been compared with an Australian isolate from nectarine. Thirteen sequence variants 336-338 nt in size were obtained. All variants clustered phylogenetically with variants reported from several hosts and countries. A total nucleic acid extract, a slightly longer than full-length RT-PCR amplicon, and a recombinant plasmid clone from the Australian isolate were all infectious to, and symptomatic in, mechanically inoculated peach seedlings. The infectious clone generated two progeny viroid molecules, which each showed 10 different mutations compared with the parent clone inoculated 30 days previously. PMID- 22075918 TI - Human sapovirus classification based on complete capsid nucleotide sequences. AB - The genetically diverse sapoviruses (SaVs) are a significant cause of acute human gastroenteritis. Human SaV surveillance is becoming more critical, and a better understanding of the diversity and distribution of the viral genotypes is needed. In this study, we analyzed 106 complete human SaV capsid nucleotide sequences to provide a better understanding of their diversity. Based on those results, we propose a novel standardized classification scheme that meets the requirements of the International Calicivirus Scientific Committee. We believe the classification scheme and strains described here will be of value for the molecular characterization and classification of newly detected SaV genotypes and for comparing data worldwide. PMID- 22075919 TI - Inhibition of fatty acid synthase by amentoflavone reduces coxsackievirus B3 replication. AB - Coxsackievirus B3 (CVB3) is a human pathogen that causes acute and chronic infections, but an antiviral drug to treat these diseases has not yet been developed for clinical use. Several intracellular pathways are altered to assist viral transcription, RNA replication, and progeny release. Among these, fatty acid synthase (FAS) expression is increased. In order to test the potential of FAS inhibition as an anti-CVB3 strategy, several experiments were performed, including studies on the correlation of CVB3 replication and FAS expression in human Raji cells and an analysis of the time and dose dependence of the antiviral effect of FAS inhibition due to treatment with amentoflavone. The results demonstrate that CVB3 infection induces an up-regulation of FAS expression already at 1 h postinfection (p.i.). Incubation with increasing concentrations of amentoflavone inhibited CVB3 replication significantly up to 8 h p.i. In addition, suppression of p38 MAP kinase activity by treatment with SB239063 decreased FAS expression as well as viral replication. These data provide evidence that FAS inhibition via amentoflavone administration might present a target for anti-CVB3 therapy. PMID- 22075920 TI - Multiple polyadenylated RNA viruses detected in pooled cultivated and wild plant samples. AB - RNA extracted from 120 leaf specimens from 17 plant species was pooled, and polyadenylated RNA species were sequenced together without barcoding in one lane using massively parallel sequencing technology. After analysis, complete or partial genome sequences representing 20 virus isolates of 16 polyadenylated RNA species were identified. In three cases, 2-3 distinct isolates of a virus species co-infected the same plant. Twelve of the viruses identified were described previously and belonged to the genera Potyvirus, Nepovirus, Allexivirus, and Carlavirus. Four were unknown and are proposed as members of the genera Potyvirus, Sadwavirus, and Trichovirus. Virus sequences were subsequently matched to original host plants using RT-PCR assays. PMID- 22075921 TI - Complete sequence of a cryptic virus from hemp (Cannabis sativa). AB - Hemp (Cannabis sativa) was found to be a useful propagation host for hop latent virus, a carlavirus. However, when virus preparations were analysed by electron microscopy, along with the expected filamentous particles, spherical particles with a diameter of around 34 nm were found. RNA from virus preparations was purified, and cDNA was prepared and cloned. Sequence information was used to search databases, and the greatest similarity was found with Primula malacoides virus 1, a putative new member of the genus Partitivirus. The full sequences of RNA 1 and RNA 2 of this new hemp cryptic virus were obtained. PMID- 22075922 TI - Low temperature conductivity of carbon nanotube aggregates. AB - We compare, over wide temperature ranges, the transport properties of single-wall carbon nanotubes arranged in the form of aligned arrays or in the form of fibres. The experimental data show that both the forms of aggregates present a crossover in the transport mechanism from three-dimensional hopping of the electrons between localized states at high temperature to fluctuation-induced tunnelling across potential barriers at low temperature. The role of the junctions formed between the bundles in the array and between the nanotubes inside the fibres is discussed on the basis of the experimental results. PMID- 22075923 TI - Optical mapping and sequencing of the Escherichia coli KO11 genome reveal extensive chromosomal rearrangements, and multiple tandem copies of the Zymomonas mobilis pdc and adhB genes. AB - Escherichia coli KO11 (ATCC 55124) was engineered in 1990 to produce ethanol by chromosomal insertion of the Zymomonas mobilis pdc and adhB genes into E. coli W (ATCC 9637). KO11FL, our current laboratory version of KO11, and its parent E. coli W were sequenced, and contigs assembled into genomic sequences using optical NcoI restriction maps as templates. E. coli W contained plasmids pRK1 (102.5 kb) and pRK2 (5.4 kb), but KO11FL only contained pRK2. KO11FL optical maps made with AflII and with BamHI showed a tandem repeat region, consisting of at least 20 copies of a 10-kb unit. The repeat region was located at the insertion site for the pdc, adhB, and chloramphenicol-resistance genes. Sequence coverage of these genes was about 25-fold higher than average, consistent with amplification of the foreign genes that were inserted as circularized DNA. Selection for higher levels of chloramphenicol resistance originally produced strains with higher pdc and adhB expression, and hence improved fermentation performance, by increasing the gene copy number. Sequence data for an earlier version of KO11, ATCC 55124, indicated that multiple copies of pdc adhB were present. Comparison of the W and KO11FL genomes showed large inversions and deletions in KO11FL, mostly enabled by IS10, which is absent from W but present at 30 sites in KO11FL. The early KO11 strain ATCC 55124 had no rearrangements, contained only one IS10, and lacked most accumulated single nucleotide polymorphisms (SNPs) present in KO11FL. Despite rearrangements and SNPs in KO11FL, fermentation performance was equal to that of ATCC 55124. PMID- 22075924 TI - Effect of modified glucose catabolism on xanthan production in Xanthomonas oryzae pv. oryzae. AB - In this study, the glucose 6-phosphate dehydrogenase gene (XOO2314) was inactivated in order to modulate the intracellular glucose 6-phosphate, and its effects on xanthan production in a wild-type strain of Xanthomonas oryzae were evaluated. The intracellular glucose 6-phosphate was increased from 17.6 to 99.4 MUmol g-1 (dry cell weight) in the gene-disrupted mutant strain. The concomitant increase in the glucose 6-phosphate was accompanied by an increase in xanthan production of up to 2.23 g l-1 (culture medium). However, in defined medium supplemented with 0.4% glucose, the growth rate of the mutant strain was reduced to 52.9% of the wild-type level. Subsequently, when a family B ATP-dependent phosphofructokinase from Escherichia coli was overexpressed in the mutant strain, the growth rate was increased to 142.9%, whereas the yields of xanthan per mole of glucose remained approximately the same. PMID- 22075925 TI - Primary percutaneous coronary intervention as a national reperfusion strategy in patients with ST-segment elevation myocardial infarction. AB - BACKGROUND: In Denmark, primary percutaneous coronary intervention (PPCI) was chosen as a national reperfusion strategy for patients with ST-segment elevation myocardial infarction in 2003. This study describes the temporal implementation of PPCI in Western Denmark, the gradual introduction of field triage for PPCI (patients rerouted from the scene of the event directly to the invasive center), and the associated outcome. METHODS AND RESULTS: The study population comprised 9514 patients treated with PPCI from 1999 to 2009 with symptom duration <=12 hours and either a delay from the emergency medical service (EMS) call to PPCI (healthcare system delay) of <=6 hours or as self-presenters. The median follow up time was 3.7 years. The number of patients treated with PPCI increased from 190 in 1999 to 1212 in 2009. Among patients transported by the EMS from the scene of the event, the proportion who were field triaged directly to a PCI center increased from 33% (34/103) to 72% (616/851, P<0.001). Patients who were field triaged had lower long-term mortality, with adjusted hazard ratios (95% CI) of 1.26 (1.12-1.43) among patients transported by the EMS to a local hospital and then transferred, 1.28 (1.10-1.49) among patients self-presenting at a local hospital and then transferred, and 1.37 (1.18-1.58) among patients self presenting at a PCI center. CONCLUSIONS: A reperfusion strategy with PPCI only for patients with ST-segment elevation myocardial infarction was successfully implemented in Western Denmark, and the majority of patients transported by the EMS are now triaged directly to the PPCI centers. This strategy is associated with lower mortality. PMID- 22075926 TI - Short-term performance of the transcatheter Melody valve in high-pressure hemodynamic environments in the pulmonary and systemic circulations. AB - BACKGROUND: The Melody valve is approved for percutaneous pulmonary valve replacement in dysfunctional right ventricular outflow tracts. The function of this valve when subjected to high-pressure loads in humans is unknown. The aim of this study was to describe the immediate and short-term results of Melody valves implanted in a high-pressure environment. METHODS AND RESULTS: Definitions of a high-pressure system were established for Melody valves implanted in the systemic (ie, aortic or mitral position) and pulmonary (ie, right ventricular outflow tract conduit or tricuspid valve annulus) circulations. Implants in these environments were ascertained from databases of the 5 centers that participated in the US Investigational Device Exemption trial. Thirty implants met the inclusion criteria: 23 pulmonary circulation implants (all in the pulmonary position) systemic circulation implants (5 in the native aortic position, 1 in a left ventricle-to-descending aorta conduit, and 1 in the mitral annulus). All pulmonary circulation implants were performed percutaneously in the catheterization laboratory. A hybrid approach (surgical exposure for transcatheter implant) was used for 4 of the aortic implants. There were no procedure-related deaths. Three patients died of nonprocedure- and nonvalve related causes. At 1 year, freedom from moderate to severe regurgitation was 100%, and freedom from mild regurgitation was 90%. Freedom from moderate to severe stenosis was 86% at 1 year. CONCLUSIONS: Short-term performance of the Melody valve in high-pressure environments is encouraging, with good valve function in all patients. PMID- 22075927 TI - Stent fracture, valve dysfunction, and right ventricular outflow tract reintervention after transcatheter pulmonary valve implantation: patient-related and procedural risk factors in the US Melody Valve Trial. AB - BACKGROUND: Among patients undergoing transcatheter pulmonary valve (TPV) replacement with the Melody valve, risk factors for Melody stent fracture (MSF) and right ventricular outflow tract (RVOT) reintervention have not been well defined. METHODS AND RESULTS: From January 2007 to January 2010, 150 patients (median age, 19 years) underwent TPV implantation in the Melody valve Investigational Device Exemption trial. Existing conduit stents from a prior catheterization were present in 37 patients (25%, fractured in 12); 1 or more new prestents were placed at the TPV implant catheterization in 51 patients. During follow-up (median, 30 months), MSF was diagnosed in 39 patients. Freedom from a diagnosis of MSF was 77+/-4% at 14 months (after the 1-year evaluation window) and 60+/-9% at 39 months (3-year window). On multivariable analysis, implant within an existing stent, new prestent, or bioprosthetic valve (combined variable) was associated with longer freedom from MSF (P<0.001), whereas TPV compression (P=0.01) and apposition to the anterior chest wall (P=0.02) were associated with shorter freedom from MSF. Freedom from RVOT reintervention was 86+/-4% at 27 months. Among patients with a MSF, freedom from RVOT reintervention after MSF diagnosis was 49+/-10% at 2 years. Factors associated with reintervention were similar to those for MSF. CONCLUSIONS: MSF was common after TPV implant in this multicenter experience and was more likely in patients with severely obstructed RVOT conduits and when the TPV was directly behind the anterior chest wall and/or clearly compressed. A TPV implant site protected by a prestent or bioprosthetic valve was associated with lower risk of MSF and reintervention. PMID- 22075928 TI - Strain-dependent induction of neutrophil histamine production and cell death by Pseudomonas aeruginosa. AB - Airway diseases often feature persistent neutrophilic inflammation and infection. In cystic fibrosis bronchitis, for example, Pseudomonas aeruginosa is isolated frequently. Previously, this laboratory revealed that neutrophils become major sources of histamine in mice with tracheobronchitis caused by the wall-less bacterium Mycoplasma pulmonis. To test the hypothesis that more-broadly pathogenic P. aeruginosa (which expresses cell wall-associated LPS and novel toxins) has similar effects, we incubated naive mouse neutrophils with two strains of P. aeruginosa. Strain PAO1 greatly increased neutrophil histamine content and secretion, whereas strain PA103 depressed histamine production by killing neutrophils. The histamine-stimulating capacity of PAO1, but not PA103 mediated toxicity, persisted in heat-killed organisms. In PAO1-infected mice, lung and neutrophil histamine content increased. However, PAO1 did not alter production by mast cells (classical histamine reservoirs), which also resisted PA103 toxicity. To explore mechanisms of neutrophil-selective induction, we measured changes in mRNA encoding histidine decarboxylase (rate-limiting for histamine synthesis), probed involvement of endotoxin-TLR pathways in Myd88 deficient neutrophils, and examined contributions of pyocyanin and exotoxins. Results revealed that PAO1 increased histamine production by up-regulating histidine decarboxylase mRNA via pathways largely independent of TLR, pyocyanin, and type III secretion system exotoxins. PAO1 also increased histidine decarboxylase mRNA in neutrophils purified from infected lung. Stimulation required direct contact with neutrophils and was blocked by phagocytosis inhibitor cytochalasin D. In summary, Pseudomonas-augmented histamine production by neutrophils is strain-dependent in vitro and likely mediated by up-regulation of histidine decarboxylase. These findings raise the possibility that Pseudomonas stimulated neutrophils can enhance airway inflammation by producing histamine. PMID- 22075929 TI - Technical advance: in vitro production of distinct dendritic-like antigen presenting cells from self-renewing hematopoietic stem cells. AB - A novel CD11c(lo)CD11b(hi)MHC-II-CD8alpha- dendritic-like cell (L-DC) develops in cocultures of bone marrow over splenic stroma. L-DCs are distinct from other DC subsets and have potential importance in spleen for immunity to blood-borne antigens. As production is maintained in cultures for >12 months, L-DC development evidently depends on self-renewing progenitors. To improve this culture system, highly purified HSCs were sorted from bone marrow and used to establish cocultures. Nonadherent cells produced were analyzed for surface marker expression and capacity to activate/inhibit T cells. Cocultures produced a pure population of L-DCs for up to 12 months, which were strong activators of CD8+ T cells. The in vitro production of a pure population of L-DCs from HSCs--in numbers amenable to in vitro assays of function and development--therefore represents an important advance. PMID- 22075931 TI - Should the diagnosis of autism be made only on the basis of a standardized test? AB - This commentary argues that a standardized tool such as Autism Diagnostic Observation Schedule (ADOS) is not always required to make the diagnosis of autism, which can be made by obtaining a thorough history and performing an astute clinical examination as William Osler, founder of John Hopkins School of Medicine, taught or Dr. Leo Kanner practiced. PMID- 22075930 TI - Macrophage-elicited osteoclastogenesis in response to Brucella abortus infection requires TLR2/MyD88-dependent TNF-alpha production. AB - Osteoarticular complications are common in human brucellosis, but the pathogenic mechanisms involved are largely unknown. In this manuscript, we described an immune mechanism for inflammatory bone loss in response to infection by Brucella abortus. We established a requirement for MyD88 and TLR2 in TNF-alpha-elicited osteoclastogenesis in response to B. abortus infection. CS from macrophages infected with B. abortus induced BMM to undergo osteoclastogenesis. Although B. abortus-infected macrophages actively secreted IL-1beta, IL-6, and TNF-alpha, osteoclastogenesis depended on TNF-alpha, as CS from B. abortus-infected macrophages failed to induce osteoclastogenesis in BMM from TNFRp55-/- mice. CS from B. abortus-stimulated MyD88-/- and TLR2-/- macrophages failed to express TNF alpha, and these CS induced no osteoclast formation compared with that of the WT or TLR4-/- macrophages. Omp19, a B. abortus lipoprotein model, recapitulated the cytokine production and subsequent osteoclastogenesis induced by the whole bacterium. All phenomena were corroborated using human monocytes, indicating that this mechanism could play a role in human osteoarticular brucellosis. Our results indicate that B. abortus, through its lipoproteins, may be involved in bone resorption through the pathological induction of osteoclastogenesis. PMID- 22075932 TI - Adenine Synthesis in a Model Prebiotic Reaction: Connecting Origin of Life Chemistry with Biology. AB - Many high school laboratory experiments demonstrate concepts related to biological evolution, but few exist that allow students to investigate life's chemical origins. This series of laboratory experiments has been developed to allow students to explore and appreciate the deep connection that exists between prebiotic chemistry, chemical evolution, and contemporary biological systems. In the first experiment of the series, students synthesize adenine, one of the purine nucleobases of DNA and RNA, from plausibly prebiotic precursor molecules. Students compare their product to authentic standards using thin-layer chromatography. The second and third experiments of the series allow students to extract DNA from a familiar organism, the strawberry, and hydrolyze it, releasing adenine, which they can then compare to the previously chemically-synthesized adenine. A fourth, optional experiment is included where the technique of thin layer chromatography is introduced and chromatographic skills are developed for use in the other three experiments that comprise this series. Concepts relating to organic and analytical chemistry, as well as biochemistry and DNA structure, are incorporated throughout, allowing this series of laboratory experiments to be easily inserted into existing laboratory courses and to reinforce concepts already included in any high school chemistry or biology curriculum. PMID- 22075933 TI - Nanocrystalline carbonate-apatites: role of Ca/P ratio on the upload and release of anticancer platinum bisphosphonates. AB - In the present study two nanocrystalline apatites have been investigated as bone specific drug delivery devices to be used for treatment of bone tumors either by local implantation or by injection. In order to assess how the Ca/P ratio can influence the adsorption and release of anticancer platinum-bisphosphonate complexes, two kinds of apatite nanocrystals having different Ca/P ratios but similar morphologies, degree of crystallinity, and surface areas have been synthesized and characterized. The two platinum-bisphosphonate complexes considered were the bis-{ethylenediamineplatinum(ii)}-2-amino-1-hydroxyethane-1,1 diyl-bisphosphonate and the bis-{ethylenediamineplatinum(ii)}medronate. The Ca/P ratio plays an important role in the adsorption as well as in the release of the two drugs. In fact, the apatite with a higher Ca/P ratio showed greater affinity for both platinum complexes. Also the chemical structure of the two Pt complexes appreciably affects their affinity towards as well as their release from the two kinds of apatites. In particular, the platinum complex whose bisphosphonate contains a free aminic group showed greater upload and smaller release. The cytotoxicity of the Pt complexes released from the apatite was tested against human cervical, colon, and lung cancer cells as well as against osteosarcoma cells. In agreement with previous work, the Pt complexes released were found to be more cytotoxic than the unmodified complexes. PMID- 22075934 TI - Syntheses of highly unsaturated isocyanides via organometallic pathways. AB - The carbon carbon coupling reaction by nucleophilic attack of (CO)(5)Cr(CN CF=CF(2)) 1 by lithium or Grignard compounds 2a-i yields the isocyanide complexes (CO)(5)Cr(CN-CF=CF-R) 3a-i (a R = CH=CH(2), b R = CH=CF(2), c R = C=CH, d R = C=C SiMe(3), e R = C=C-Ph, f R = C=C-C(6)F(4)OMe, g R = C=C-C(6)H(3)(CF(3))(2), h R = C(6)F(5), i R = C(6)H(3)(CF(3))(2)) as mixtures of E and Z isomers. The dinuclear complexes 5a-c are obtained from the reaction of 1 with the dilithio or dimagnesium compound 4a-c as the Z,Z-, E,Z- and E,E-isomers, respectively. (CO)(5)Cr(CN-CF=CF-C=C-C=C-CF=CF-NC)Cr(CO)(5)7 is obtained as a mixture of Z,Z-, Z,E- and E,E-isomers from (CO)(5)Cr(CN-CF=CF-C=C-H 3d by Eglington-Glaser coupling. (CO)(5)Cr(CN-CF=CF-C=C-CF=CF-NC)Cr(CO)(5)6 and (CO)(5)Cr(CN-CF=CF-C=C C=C-CF=CF-NC)Cr(CO)(5)7 react with octacarbonyldicobalt forming the cluster compounds Z,Z-[{eta(2)-MU(2)-(CO)(5)Cr(CN-CF=CF-C=C-CF=CF NC)Cr(CO)(5)}Co(2)(CO)(6)] Z,Z-8, E,Z-[{eta(2)-MU(2)-(CO)(5)Cr(CN-CF=CF-C=C-CF=CF NC)Cr(CO)(5)}Co(2)(CO)(6)] E,Z-8 and E,E-[{eta(2)-MU(2)-(CO)(5)Cr(CN-CF=CF-C=C CF=CF-NC)Cr(CO)(5)}Co(2)(CO)(6)] E,E-8 and Z,Z-[{eta(2)-MU(2)-(CO)(5)Cr(CN-CF=CF C=C-C=C-CF=CF-NC)Cr(CO)(5)}{Co(2)(CO)(6)}(2)] Z,Z-9, E,Z-[{eta(2)-MU(2) (CO)(5)Cr(CN-CF=CF-C=C-C=C-CF=CF-NC)Cr(CO)(5)}{Co(2)(CO)(6)}(2)] E,Z-9 and E,E [{eta(2)-MU(2)-(CO)(5)Cr(CN-CF=CF-C=C-C=C-CF=CF-NC)Cr(CO)(5)}{Co(2)(CO)(6)}(2)] Z,Z-9, respectively. The crystal and molecular structures of E-3d, Z-3h, Z,Z-8, E,Z-8 and Z,Z-9 were elucidated by single-crystal X-ray crystallography. PMID- 22075936 TI - Developmental Systems Theory Formulated as a Claim about Inherited Representations* AB - Developmental systems theory (DST) is often dismissed on the basis that the causal indispensability of nongenetic factors in evolution and development has long been appreciated. A reformulation makes a more substantive claim: that the special role played by genes is also played by some (but not all) nongenetic resources. That special role can be captured by Shea's 'inherited representation'. Formulating DST as the claim that there are nongenetic inherited representations turns it into a striking, empirically testable hypothesis. DST's characteristic rejection of a gene versus environment dichotomy is preserved but without dissolving into an interactionist casual soup, as some have alleged. PMID- 22075935 TI - Double-stranded RNA-induced TLR3 activation inhibits angiogenesis and triggers apoptosis of human hepatocellular carcinoma cells. AB - Toll-like receptor 3 (TLR3) is a member of the Toll-like receptors which recognize pathogen-associated molecular patterns leading to the activation of the innate immune response. Recent reports have strongly indicated that they play important roles in cancer cells. Since TLR3 has been recently suggested as a possible therapeutic target in certain types of cancers, in the present study, TLR3 expression and its function were explored in hepatocellular carcinoma (HCC) and human umbilical vein endothelial cells (HUVECs). The expression of TLR3 in various HCC cell lines and HUVECs was detected using quantitative real-time PCR (qRT-PCR) and immunocytochemistry. TLR3 activity was determined by Luciferase reporter assays. The effects of TLR3 double-stranded RNA (dsRNA) agonists on angiogenesis were tested by aortic ring assay and HUVEC tube formation experiments. After dsRNA treatment, cell apoptosis was assessed by Annexin V and PI staining through FACS, and the migration ability was measured by a migration assay. The results showed that TLR3 was expressed in HCC cell lines and HUVECs at the mRNA and protein level. Luciferase reporter assays demonstrated that TLR3 was activated by the dsRNA analog BM-06 or poly(I:C). Rat aortic ring outgrowth and endothelial cell tube formation were suppressed after treatment with dsRNA. In addition, dsRNA triggered apoptosis in MHCC97H, SMMC-7721 and HUVEC cell lines and inhibited cell migration. In conclusion, TLR3 agonists not only affect tumor microenvironment by suppressing angiogenesis but also directly induce tumor cell apoptosis and inhibit tumor cell migration. TLR3 may be a new target for HCC therapy. PMID- 22075937 TI - Postoperative immune suppression in visceral surgery: characterisation of an intestinal mouse model. AB - BACKGROUND: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. METHODS: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. RESULTS: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. CONCLUSIONS: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome. PMID- 22075938 TI - Clobetasol synergistically diminishes Ciz1 expression with genistein in U937 cells. AB - Cip-interacting zinc finger protein 1 (Ciz1) stimulates DNA replication and has been implicated in the tumorigenesis of breast cancer cells. In order to investigate the possibility of using medicinal glucocorticoids against breast cancer, we studied whether certain glucocorticoids affect the expression of Ciz1. The in vitro effect of clobetasol treatment on the reduction of Ciz1 expression was detected by reverse transcriptase-polymerase chain reaction. Western blotting also confirmed the down-regulation of the protein in a dose-dependent manner upon clobetasol treatment in U937 monocytoid cells. Furthermore, we found that Ciz1 protein expression was decreased after pre-treatment of the cells with clobetasol and genistein. An extract of Lens culinaris also had a synergistic effect on the repression of Ciz1 protein expression. PMID- 22075939 TI - A hybrid biocathode: surface display of O2-reducing enzymes for microbial fuel cell applications. AB - Laccase and bilirubin oxidase were successfully displayed on the surface of yeast cells. Subsequently, these modified yeast cells were used in the cathode compartment of a microbial fuel cell. The performance of the fuel cells is compared. PMID- 22075940 TI - Overview of contemporary issues of forest research and management in China. AB - With 207 million ha of forest covering 22% of its land area, China ranks fifth in the world in forest area. Rapid economic growth, climate change, and forest disturbances pose new, complex challenges for forest research and management. Progress in meeting these challenges is relevant beyond China, because China's forests represent 34% of Asia's forests and 5% of the worlds' forests. To provide a broader understanding of these management challenges and of research and policies that address them, we organized this special issue on contemporary forest research and management issues in China. At the national level, papers review major forest types and the evolution of sustainable forestry, the development of China's forest-certification efforts, the establishment of a forest inventory system, and achievements and challenges in insect pest control in China. Papers focused on Northern China address historical, social, and political factors that have shaped the region's forests; the use of forest landscape models to assess how forest management can achieve multiple objectives; and analysis and modeling of fuels and fire behavior. Papers addressing Central and South China describe the "Grain for Green" program, which converts low productivity cropland to grassland and woodland to address erosion and soil carbon sequestration; the potential effects of climate change on CO(2) efflux and soil respiration; and relationships between climate and net primary productivity. China shares many forest management and research issues with other countries, but in other cases China's capacity to respond to forest management challenges is unique and bears watching by the rest of the world. PMID- 22075941 TI - Predictive factors for the objective burden of informal care in people with dementia: a systematic review. AB - BACKGROUND: Informal care plays a substantial role in the provision of total care in dementia. Several reviews have been published on the predictive factors of subjective burden; however, such a review lacks information on objective burden, which refers to the amount and/or costs of informal care. OBJECTIVES: The objectives of this study were to (1) give an overview of the predictive factors that are associated with the objective burden of informal care; (2) discuss whether these factors are similar to the predictive factors of subjective burden; and (3) examine whether they are modifiable. DESIGN: The literature in a number of international databases was systematically searched. Methodological quality and level of certainty were assessed. RESULTS: Ten studies were identified as relevant for the purpose of this review, describing a total of 39 predictive factors. Three factors (behavioral problems and impairments regarding daily functioning and cognition) were considered to be predictors of objective burden. Three factors were not related; 12 were potential predictors; and the results of the remaining 22 factors were inconclusive. CONCLUSIONS: Many factors were found to be (potential) predictors of objective burden, reflecting its complex nature. Objective and subjective burdens are 2 different relevant aspects of informal care. Interventions aimed at countering behavioral problems and impairments regarding daily functioning could reduce objective burden. PMID- 22075942 TI - Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. AB - BACKGROUND: Cervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities. METHODS: We conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality. RESULTS: Of the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4-1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4 2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6-1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9-1.4). Diindolylmethane supplementation was well tolerated. CONCLUSION: The results suggest that short term DIM supplementation (150 mg day(-1)) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+. PMID- 22075943 TI - Expression of CIP2A in renal cell carcinomas correlates with tumour invasion, metastasis and patients' survival. AB - BACKGROUND: Cancerous inhibitor of protein phosphatase 2A (CIP2A) drives cellular transformation. The objective of this study was to detect the potential effects of CIP2A in renal cell carcinomas (RCCs). METHODS: A total of 107 RCC patients were involved in the study. Cancerous inhibitor of protein phosphatase 2A expression was investigated by real-time PCR and immunohistochemistry. In vitro, we examined the expression of CIP2A and c-Myc and tested the migration and invasion capability of A498 and KRC/Y cells with scratch migration assay and Matrigel invasion assay after down-regulating CIP2A expression using siRNA. RESULTS: Cancerous inhibitor of protein phosphatase 2A was over-expressed in RCC tissues. Clear cell RCC showed an even higher-CIP2A expression level than papillary or chromophobe RCC did. The CIP2A immunostaining level was positively correlated with primary tumour stage, lymph node metastasis, distant metastasis, TNM stage and histological grade (all P<0.05). High-CIP2A expression implied poor survival for patients (P<0.05). Cancerous inhibitor of protein phosphatase 2A depletion by siRNA down-regulated c-Myc expression and attenuated the migration and invasion of RCC cells. CONCLUSION: Higher-CIP2A expression positively correlates with the aggressive phenotype of RCCs, and predicts poor prognosis for patients. Cancerous inhibitor of protein phosphatase 2A may be a novel target for prevention and treatment of RCC metastasis and recurrence. PMID- 22075944 TI - Aspirin as adjuvant therapy in childhood cancer? PMID- 22075945 TI - Identification of markers of prostate cancer progression using candidate gene expression. AB - BACKGROUND: Metastatic prostate cancer (PCa) has no curative treatment options. Some forms of PCa are indolent and slow growing, while others metastasise quickly and may prove fatal within a very short time. The basis of this variable prognosis is poorly understood, despite considerable research. The aim of this study was to identify markers associated with the progression of PCa. METHODS: Artificial neuronal network analysis combined with data from literature and previous work produced a panel of putative PCa progression markers, which were used in a transcriptomic analysis of 29 radical prostatectomy samples and correlated with clinical outcome. RESULTS: Statistical analysis yielded seven putative markers of PCa progression, ANPEP, ABL1, PSCA, EFNA1, HSPB1, INMT and TRIP13. Two data transformation methods were utilised with only markers that were significant in both selected for further analysis. ANPEP and EFNA1 were significantly correlated with Gleason score. Models of progression co-utilising markers ANPEP and ABL1 or ANPEP and PSCA had the ability to correctly predict indolent or aggressive disease, based on Gleason score, in 89.7% and 86.2% of cases, respectively. Another model of TRIP13 expression in combination with preoperative PSA level and Gleason score was able to correctly predict recurrence in 85.7% of cases. CONCLUSION: This proof of principle study demonstrates a novel association of carcinogenic and tumourigenic gene expression with PCa stage and prognosis. PMID- 22075946 TI - Notch signalling in cancer progression and bone metastasis. AB - Classically known for its indispensible role in embryonic development, the Notch signalling pathway is gaining recognition for its regulation of adult tissue homoeostasis and aberrant activation in disease pathogenesis. The pathway has been implicated in cancer initiation and development, as well as early stages of cancer progression by regulating conserved cellular programs such as the epithelial-to-mesenchymal transition. We recently extended the role of Notch signalling to late stages of tumour progression by elucidating a stroma-dependent mechanism for the pathway in osteolytic bone metastasis. Of clinical significance, disrupting the Notch pathway and associated molecular mediators of Notch-dependent bone metastasis may provide novel therapeutic strategies to combat aggressive bone metastatic disease. PMID- 22075947 TI - Changes in protein expression in the sheep abomasum following trickle infection with Teladorsagia circumcincta. AB - Continual low-level exposure of sheep to the helminth Teladorsagia circumcincta elicits a temporary protective immunity, where factors in the immune abomasal mucosa prevent penetration of infective larvae, but which is essentially lost within 6 weeks of cessation of parasite challenge. Here, a proteomic approach was used to identify proteins that are differentially regulated in immune compared to naive sheep, as potential key mediators of immunity. Six naive sheep and 12 sheep trickle-infected with T. circumcincta were treated with anthelmintic, and the naive (control) and 6 immune sheep were killed 7 days later. The remaining 6 sheep (immune waning) were killed 42 days after anthelmintic treatment. Abomasal tissue samples were subjected to 2D-gel electrophoresis and densitometric analysis. Selected spots (n=73) were identified by peptide mass fingerprinting and confirmatory Western blotting was carried out for 10 proteins. Spots selectively up-regulated in immune versus control, but not immune waning versus control sheep, included galectin-15 and thioredoxin, which were confirmed by Western blotting. In immune sheep, serum albumin was significantly down-regulated and albumin proteolytic cleavage fragments were increased compared to controls. Unexpectedly, albumin mRNA was relatively highly expressed in control mucosa, down-regulated in immune, and was immunolocalized to mucus-producing epithelial cells. Thus we have identified differential expression of a number of proteins following T. circumcincta trickle infection that may play a role in host protection and inhibition of parasite establishment. PMID- 22075948 TI - Mossbauer investigations of crystalline and quasicrystalline Al3(Mn, Fe) compounds. AB - (57)Fe Mossbauer and magnetic measurements are reported on Taylor phase compounds T-Al(3)(Mn,Fe), which can be seen as complex metallic alloys. The orthorhombic unit cell contains 156 atoms. These investigations are further extended to Al(71)Mn(19)Fe(10) crystallizing as a decagonal quasicrystal. Common to both structures are layers, which are oriented perpendicular to the b axis in the crystalline or to the periodic axis in the quasicrystalline compound, allowing the formation of characteristic building blocks. At low temperatures for all samples spin glass behavior is observed with freezing temperatures T(f) increasing with Fe content. Above T(f) the (57)Fe Mossbauer spectra were analyzed by a superposition of two subspectra with intensity ratio around 75:25, which can be allocated to Fe substituted on Mn sites surrounded either by Al and Mn or solely by Al with Mn only at the edge of the nearest neighbor shell. For both subspectra quadrupole splitting and center shift do not change significantly with Fe content and with structure. Below T(f) broad hyperfine field distributions with non-vanishing contributions at zero hyperfine field are present. Magnetic and electrostatic hyperfine interactions are governed by length scales which are determined by the very similar interatomic configurations forming the T-Al(3)Mn phase as well as the decagonal compound. The presence of long range atomic order is of less importance. PMID- 22075949 TI - SAME-GENDER SEX AMONG U.S. ADULTS: TRENDS ACROSS THE TWENTIETH CENTURY AND DURING THE 1990s. AB - Trends in reporting of same-gender sex are assessed using data from the 1988-2002 General Social Surveys (Ns = 9,487 males and 12,336 females). Analyses indicate that the reported prevalence of female-female sexual contact increased substantially and monotonically across twentieth-century birth cohorts, rising from 1.6 percent (Standard error [SE] = 0.60) for the cohort of U.S. women born prior to 1920 to 6.9 percent (SE = 0.81) for women born in 1970 and afterward. Increases in the reported prevalence of female-female contacts also occurred within the 1990s. These trends persist when statistical controls are introduced for changes in attitudes toward same-gender sexual behavior. No parallel trend is observed in the reporting of male-male sexual contacts during adulthood, although the proportion of U.S. men reporting such contacts in the past year and in the past five years increased during the 1990s. PMID- 22075951 TI - Combination therapy of conditionally replicating adenovirus and histone deacetylase inhibitors. AB - Combination therapy of adenoviral gene therapy and a histone deacetylase (HDAC) inhibitor is important due to the enhancing effect of HDAC inhibitors on adenoviral transduction and transcription. However, contradictory results have been reported on the effect of combination of CRAd (conditionally replicating adenovirus) and HDAC inhibitors. This study was designed to investigate the interaction of CRAd and HDAC inhibitors and determine the ideal way to combine the two agents. Combination of HDAC inhibitors (SK7041, SBHA and vorinostat) at pre- and post-transductional periods with CRAd enhanced the transduction of CRAd and expression of luciferase expression from Delta24-luc in vitro. However, suppression of luciferase expression from Delta24-luc injected tumor mass was observed by in vivo tumor bioluminescence imaging and drug interaction analysis also showed an antagonistic interaction that was probably related with the inhibitory effect of the HDAC inhibitor on adenoviral replication. Suppression of p21 induction by p21 siRNA reversed the suppressive effect of vorinostat on the replication of CRAd, but still failed to reverse the antagonistic interaction. Addition of vorinostat at the pre-transductional period revealed an improvement in the transduction efficiency of CRAd and also induced a synergistic interaction between CRAd and vorinostat, which was possibly related with prevention of the suppressive effect of vorinostat on adenoviral replication. In conclusion, the addition of HDAC inhibitor before CRAd injection showed synergistic antitumor effects, which warrants further investigation on the sequence of HDAC inhibitor and CRAd treatment in an animal tumor model. PMID- 22075950 TI - High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus. AB - Retinoic acid, the active form of the nutrient vitamin A, regulates several facets of neuronal plasticity in the hippocampus, including neurogenesis and synaptic strength, acting via specific retinoic acid receptors (RARs). Essential for conversion of vitamin A to retinoic acid is the enzyme retinaldehyde dehydrogenase (RALDH) and in the rodent hippocampus this is only present in the adjacent meninges where it must act as a locally released paracrine hormone. Little is known though about the expression of RALDHs and RARs in the human hippocampus. This study confirms that RALDH levels are very low in mouse neurons but, surprisingly, strong expression of RALDH protein is detected by immunohistochemistry in hippocampal neurons. The receptors RARalpha, beta and gamma were also detected, each receptor exhibiting differing subcellular locations implying their potential regulation of both transcription and non genomic actions. These results imply an essential function of retinoic acid in the human hippocampus likely to include regulation of neuronal plasticity. PMID- 22075952 TI - Hypertension after kidney transplantation: an important, but still neglected issue. PMID- 22075953 TI - Being born too small, too early or both, does it stiffen our arteries in adult life? PMID- 22075954 TI - The morning blood pressure surge: a dynamic and challenging concept. PMID- 22075955 TI - Hypertensive disorders during pregnancy: clinical applicability of risk prediction models. PMID- 22075956 TI - Travel distance estimation for carotid femoral pulse wave velocity: is the gold standard a real one ? PMID- 22075958 TI - Effects of statin treatment on endothelial function, oxidative stress and inflammation in patients with arterial hypertension and normal cholesterol levels. PMID- 22075962 TI - Characteristics of male attendees of health education interventions for Latinos. AB - Latino subgroups in the US often shoulder a greater burden of some common diseases, including cancer. The cultural norm of patriarchy in health-related decision-making has been found to be common among Latinos, and thus male members may be important in the adoption of health practices amongst family members. Demographic information was collected from 488 male attendees (20% of the total sample) as part of a larger randomized trial focused on promoting breast and cervical cancer screening among Latinas in which attendance was open to the entire community. The majority of male attendees were over the age of 40 (62%) and originally from Mexico (39%) or Puerto Rico (25%). Approximately half of attendees reported having no health coverage and living less than 5 years in the United States. Male attendees demonstrated significant increases in knowledge relevant to their group attendance. There were few significant differences between the characteristics of male attendees at a female focused cancer program (intervention) versus more general diabetes program (control). The current study describes characteristics of a group that may be influential in guiding health behaviors and decisions. This information extends our understanding of community participation in health interventions and will assist in the development of effective interventions in the Latino community. PMID- 22075963 TI - Bio-inspired hierarchical self-assembly of nanotubes into multi-dimensional and multi-scale structures. AB - As inspired from nature's strategy to prepare collagen, herein we report a hierarchical solution self-assembly method to prepare multi-dimensional and multi scale supra-structures from the building blocks of pristine titanate nanotubes (TNTs) around 10 nm. With the help of amylose, the nanotubes was continuously self-assembled into helically wrapped TNTs, highly aligned fibres, large bundles, 2D crystal facets and 3D core-shell hybrid crystals. The amyloses work as the glue molecules to drive and direct the hierarchical self-assembly process extending from microscopic to macroscopic scale. The whole self-assembly process as well as the self-assembly structures were carefully characterized by the combination methods of (1)H NMR, CD, Hr-SEM, AFM, Hr-TEM, SAED pattern and EDX measurements. A hierarchical self-assembly mechanism was also proposed. PMID- 22075964 TI - Effects of labeling and interpersonal contact upon attitudes towards schizophrenia: implications for reducing mental illness stigma in urban China. AB - PURPOSE: As mental illness stigma contributes to poor outcomes for schizophrenia in China, locating strategies to reduce public stigma is imperative. It is currently unknown whether diagnostic labeling and contact with different help seeking sources increase or decrease public stigma in China. Further, it remains unresolved whether prior personal contact acts to reduce stigma in this context. Advancing understanding of these processes may facilitate stigma-reduction strategies. METHODS: We administered an experimental vignette randomly assigning one of four labeling conditions to respondents to assess social distance towards a psychotic vignette individual in a sample of 160 Northern, urban Chinese community respondents. RESULTS: As expected, respondents given a "non psychiatric, indigenous label" + "lay help-seeking" condition endorsed the least social distance. Unexpectedly, the labeling condition with a "psychiatric diagnostic label" + "lay help-seeking" condition elicited the greatest social distance. Unlike Western studies, personal contact did not independently decrease community stigma. However, prior contact reduced social distance to a greater extent in the labeling condition with a "non-psychiatric, indigenous label" + "lay help-seeking" condition when compared with all other labeling conditions. CONCLUSION: The results indicate that cultural idioms do provide some protection from stigma, but only among respondents who are already familiar with what mental illness is. Our finding that the condition that depicted untreated psychosis elicited the greatest amount of stigma, while the "treated psychosis" condition was viewed relatively benignly in China, suggests that improved access to mental health services in urban China has the potential to decrease public stigma via labeling mechanisms. PMID- 22075965 TI - Induction of pluripotent stem cells from fetal and adult cynomolgus monkey fibroblasts using four human transcription factors. AB - Induced pluripotent stem (iPS) cells have the potential to become a universal resource for cell-based therapies in regenerative medicine; however, prior to the use of such iPS cell-based therapies, preclinical assessment of their safety and efficacy is essential. Non-human primates serve as valuable animal models for human diseases or biomedical research; therefore, in this study, we generated cynomolgus monkey iPS cells from adult skin and fetal fibroblast cells by the retrovirally mediated introduction of four human transcription factors: c-Myc, Klf4, Oct3/4, and Sox2 (the so-called "Yamanaka factors"). Twenty to 30 days after the introduction of these factors, several cynomolgus monkey embryonic stem (ES) cell-like colonies appeared on SNL and mouse embryonic fibroblast (MEF) feeder layers. These colonies were picked and cultivated in primate ES medium. Seven iPS cell lines were established, and we detected the expression of pluripotent markers that are also expressed in ES cells. Reverse transcription polymerase chain reaction (PCR) showed that these iPS cells expressed endogenous c-Myc, Klf4, Oct3/4, and Sox2 genes, whereas several transgenes were silenced. Embryoid body and teratoma formation showed that the cynomolgus iPS cells had the developmental potential to differentiate into cells of all three primary germ layers. In summary, we generated cynomolgus monkey iPS cells by retrovirus mediated transduction of the human transcription factors, c-Myc, Klf4, Oct3/4, and Sox2 into adult cynomolgus monkey skin cells and fetal fibroblasts. The cynomolgus monkey is the most relevant primate model for human disease, and the highly efficient generation of monkey iPS cells would allow investigation of the treatments of various diseases in this model via therapeutic cloning. PMID- 22075966 TI - Patient satisfaction questionnaire for medical students' performance in a hospital outpatient clinic: a cross-sectional study. AB - Medical education in Japan has undergone significant reforms. Patient perspective and outcome have been highly valued in curricular reforms. Therefore, we evaluated an undergraduate curriculum particularly on communication skills by comparing outpatient satisfaction before and after the reforms implemented at Saga Medical School. Cross-sectional study was conducted at the General Medicine Clinic of Saga University Hospital in 1999 and 2009. A total of 729 newcomer patients evaluated 159 students; namely, 287 patients evaluated sixth-year medical students (n = 82) in 1999, and in 2009, 442 patients evaluated fifth-year medical students (n = 77). Students interviewed newcomer patients prior to a faculty's clinical examination. After a student-patient encounter, the patient was asked to fill in six-item Patient Satisfaction Questionnaire (PSQ) developed by the American Board of Internal Medicine. Mixed model two-way analysis of variance (ANOVA) with covariant of students' gender was conducted. Effect sizes were calculated to evaluate the amplitude of influence. The average score in 2009 was significantly higher than that in 1999 (3.63 +/- 0.62 versus 3.36 +/- 0.66; p < 0.001). Since the "encouraging and answering questions" and "clear explanations" were lower than those of the other items (3.24 +/- 0.98 and 3.46 +/- 0.85), these two items showed the most significant improvements (Phi coefficient = 0.31 and 0.24, p < 0.001). Thus, students' performance has improved since 1999, which may represent the success of curricular reforms at Saga Medical School. We propose that "encouraging and answering questions" and "clear explanations" should be emphasized in interview training. PMID- 22075967 TI - p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation. AB - BACKGROUND: Diabetic cardiomyopathy is characterized by energetic dysregulation caused by glucotoxicity, lipotoxicity, and mitochondrial alterations. p53 and its downstream mitochondrial assembly protein, synthesis of cytochrome c oxidase 2 (SCO2), are important regulators of mitochondrial respiration, whereas the involvement in diabetic cardiomyopathy remains to be determined. METHODS AND RESULTS: The role of p53 and SCO2 in energy metabolism was examined in both type I (streptozotocin [STZ] administration) and type II diabetic (db/db) mice. Cardiac expressions of p53 and SCO2 in 4-week STZ diabetic mice were upregulated (185% and 152% versus controls, respectively, P<0.01), with a marked decrease in cardiac performance. Mitochondrial oxygen consumption was increased (136% versus control, P<0.01) in parallel with augmentation of mitochondrial cytochrome c oxidase (complex IV) activity. Reactive oxygen species (ROS)-damaged myocytes and lipid accumulation were increased in association with membrane-localization of fatty acid translocase protein FAT/CD36. Antioxidant tempol reduced the increased expressions of p53 and SCO2 in STZ-diabetic hearts and normalized alterations in mitochondrial oxygen consumption, lipid accumulation, and cardiac dysfunction. Similar results were observed in db/db mice, whereas in p53-deficient or SCO2 deficient diabetic mice, the cardiac and metabolic abnormalities were prevented. Overexpression of SCO2 in cardiac myocytes increased mitochondrial ROS and fatty acid accumulation, whereas knockdown of SCO2 ameliorated them. CONCLUSIONS: Myocardial p53/SCO2 signal is activated by diabetes-mediated ROS generation to increase mitochondrial oxygen consumption, resulting in excessive generation of mitochondria-derived ROS and lipid accumulation in association with cardiac dysfunction. PMID- 22075968 TI - Increased asymmetric dimethylarginine (ADMA) dimethylaminohydrolase (DDAH) activity in childhood hypercholesterolemia type II. AB - Asymmetric dimethylarginine (ADMA) systemic concentrations are elevated in hypercholesterolemic adults and contribute to nitric oxide (NO) dependent endothelial dysfunction. Decreased activity of the key ADMA-hydrolyzing enzyme dimethylarginine dimethylaminohydrolase (DDAH) may be involved. Yet, the ADMA/DDAH/NO pathway has not been investigated in childhood hypercholesterolemia. We studied 64 children with hypercholesterolemia type II (HCh-II) and 54 normocholesterolemic (NCh) children (mean +/- SD; age, years: 11.1 +/- 3.5 vs. 11.9 +/- 4.6). Plasma and urine ADMA was measured by GC-MS/MS. Dimethylamine (DMA), the ADMA metabolite, creatinine, nitrite and nitrate in urine were measured by GC-MS. The DMA/ADMA molar ratio in urine was calculated to estimate whole body DDAH activity. ADMA plasma concentration (mean +/- SD; nM: 571 +/- 85 vs. 542 +/- 110, P = 0.17) and ADMA urinary excretion rate (mean +/- SD: 7.1 +/- 2 versus 7.2 +/- 3 MUmol/mmol creatinine, P = 0.6) were similar in HCh-II and NCh children. Both DMA excretion rate [median (25th-75th percentile): 56.3 (46.4 109.1) vs. 45.2 (22.2-65.5) MUmol/mmol creatinine, P = 0.0004] and DMA/ADMA molar ratio [median (25th-75th percentile): 9.2 (6.0-16.3) vs. 5.4 (3.8-9.4), P = 0.0004] were slightly but statistically significantly increased in HCh-II children compared to NCh children. Plasma and urinary nitrite and nitrate were similar in both groups. In HCh-II whole body DDAH activity is elevated as compared to NCh. HCh-II children treated with drugs for hypercholesterolemia had lower plasma ADMA levels than untreated HCh-II or NCh children, presumably via increased DDAH activity. Differences between treated and untreated HCh-II children were not due to differences in age. In conclusion, HCh-II children do not have elevated ADMA plasma levels, largely due to an apparent increase in DDAH activity. While this would tend to limit development of endothelial dysfunction, it is not clear whether this might be medication-induced or represent a primary change in HCh-II children. PMID- 22075969 TI - A novel Zn(4)O-based triazolyl benzoate MOF: synthesis, crystal structure, adsorption properties and solid state 13C NMR investigations. AB - The newly synthesized Zn(4)O-based MOF (3)(infinity)[Zn(4)(MU(4)-O){(Metrz pba)(2)mPh}(3)].8 DMF (1.8 DMF) of rare tungsten carbide (acs) topology exhibits a porosity of 43% and remarkably high thermal stability up to 430 degrees C. Single crystal X-ray structure analyses could be performed using as-synthesized as well as desolvated crystals. Besides the solvothermal synthesis of single crystals a scalable synthesis of microcrystalline material of the MOF is reported. Combined TG-MS and solid state NMR measurements reveal the presence of mobile DMF molecules in the pore system of the framework. Adsorption measurements confirm that the pore structure is fully accessible for nitrogen molecules at 77 K. The adsorptive pore volume of 0.41 cm(3) g(-1) correlates well with the pore volume of 0.43 cm(3) g(-1) estimated from the single crystal structure. PMID- 22075970 TI - What is the proper precursor-to-product labeling relationship for calculating the fractional synthetic rate of muscle triglyceride? PMID- 22075971 TI - Expression of endothelial factors in prostate cancer: a possible role of caveolin 1 for tumour progression. AB - Solid tumours need to induce their own vascular supply, and microvessel density (MVD) has emerged as a prognostic factor in several tumours. We hypothesized that mRNA levels of some endothelial factors in prostate cancer tissue would correlate with histologically measured MVD, or other pathological parameters. Expression levels of the endothelial factors CD31, CD34, CD105, CD144, CD146, CAV1 and VEGFR2 were assessed by RT-qPCR in matched freshly frozen normal and tumour tissues from 69 patients that underwent radical prostatectomy. The results were compared to pathological parameters and the MVD in the corresponding paraffin embedded material, as determined by immunohistochemistry against CD31 and CD34. Comparing mRNA expression in matched normal and tumour samples, only CAV1 showed relevant differences, being down-regulated in tumour tissues (fold change=-1.89, P<0.0001). CAV1 down-regulation correlated with pT category (P=0.006) and the Gleason score (P=0.041). In a univariate analysis, lower CAV1 mRNA expression was associated with biochemical recurrence (P=0.019). By immunohistochemistry, CAV1 was mainly localized in endothelial and stromal cells and showed a weaker staining pattern in the tumour compared to normal tissue. Furthermore, MVD significantly correlated with tumour grade and pT category. There was no significant association between endothelial mRNA expression and histologically determined MVD in tumour tissues, but only a trend for CD31 mRNA (P=0.074) and an inverse trend for CAV1 mRNA (P=0.056). In conclusion, there is only a weak correlation between the mRNA expression of endothelial factors and MVD in prostatic tumour tissue. However, loss of CAV1 mRNA expression may play a role in prostate cancer progression. PMID- 22075972 TI - Blood cardioplegia serves as a bicarbonate donor to the myocardium during ischemia: effects of anoxia and hypercapnia on acid-base characteristics of blood cardioplegic solution. AB - OBJECTIVES: We investigated the alterations of acid-base characteristics of the blood cardioplegia (BCP) solution during aortic cross-clamping in hearts arrested with BCP and during in vitro-simulated ischemia. METHODS: Following aortic cross clamping, the hearts of 40 patients undergoing cardiac surgery were intermittently infused with an 18 degrees C BCP solution and finally with a 34 degrees C BCP solution prior to aortic cross-clamp release. We measured the pH, partial CO(2) pressure (pCO(2)), [HCO(3)(-)], and [Cl(-)] of the coronary sinus effluent in the final BCP solution. The BCP solution was assessed under in vitro gassing at 34 degrees C with 95% N(2) + 5% CO(2) (n = 6), 50% N(2) + 50% CO(2) (n = 3), or 100% CO(2) (n = 6). RESULTS: The coronary sinus effluent, compared with the preinfusion BCP solution, exhibited a significantly lower pH and a greater pCO(2) with no change in the [HCO(3)(-)] level. In vitro, the 95% N(2) + 5% CO(2) gassing (simulated hypoxia) group exhibited a slight increase in [HCO(3)(-)] with no change in pCO(2) or pH whereas the 50% N(2) + 50% CO(2) gassing and the 100% CO(2) gassing (simulated hypoxia and hypercapnia) groups exhibited a significant increase in [HCO(3)(-)] under high pCO(2)-induced acidification. CONCLUSIONS: Under anoxia and CO(2) retention during aortic cross-clamping, the BCP solution can be a bicarbonate donor to the myocardium. PMID- 22075973 TI - Construction of a six-membered fused N-heterocyclic ring via a new 3-component reaction: synthesis of (pyrazolo)pyrimidines/pyridines. AB - A conceptually new three-component reaction was developed to construct a six membered fused N-heterocyclic ring affording (pyrazolo)pyrimidines/pyridines as potential inhibitors of PDE4. The reaction is catalyzed by triflic acid in acetic acid in the presence of aerial oxygen. PMID- 22075974 TI - The origin of the pseudogap in alpha-Ga. AB - Density functional theory, the free-electron empty lattice approximation and the nearly free-electron approximation are employed to investigate the electronic properties of partially covalent alpha-Ga. Whereas free-electron-like properties are revealed over a large energy range, a deep pseudogap at the Fermi level is characteristic of alpha-Ga. We explain the origin of the pseudogap in terms of a delicate interplay between the electronic states and the specific Brillouin zone geometry. PMID- 22075975 TI - Geranylgeranylacetone protects against myocardial ischemia and reperfusion injury by inhibiting high-mobility group box 1 protein in rats. AB - The high mobility group box 1 (HMGB1) protein plays an important role in myocardial ischemia and reperfusion (I/R) injury. Geranylgeranylacetone (GGA), a heat shock protein 72 inducer, has been reported to reduce myocardial I/R injury. The aim of this study was to investigate the cardioprotective mechanism of GGA during myocardial I/R injury in rats. Anesthetized male rats were treated once with GGA (200 mg/kg, p.o.) 24 h before ischemia, and subjected to ischemia for 30 min, followed by reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) activity and infarct size were measured. HMGB1 expression was assessed by immunoblotting. The results showed that pre-treatment with GGA (200 mg/kg) significantly reduced the infarct size and the levels of LDH and CK after 4 h of reperfusion (all P<0.05). GGA also significantly inhibited the increase in MDA levels and the decrease in SOD levels (both P<0.05). Meanwhile, GGA considerably suppressed the expression of HMGB1 induced by I/R. The present study suggests that GGA is capable of attenuating myocardial I/R injury by inhibiting HMGB1 expression. PMID- 22075976 TI - Genetic diversity of Babesia bovis in virulent and attenuated strains. AB - The aim of this study was to compare the genetic diversity of the single copy Bv80 gene sequences of Babesia bovis in populations of attenuated and virulent parasites. PCR/ RT-PCR followed by cloning and sequence analyses of 4 attenuated and 4 virulent strains were performed. Multiple fragments in the range of 420 to 744 bp were amplified by PCR or RT-PCR. Cloning of the PCR fragments and sequence analyses revealed the presence of mixed subpopulations in either virulent or attenuated parasites with a total of 19 variants with 12 different sequences that differed in number and type of tandem repeats. High levels of intra- and inter strain diversity of the Bv80 gene, with the presence of mixed populations of parasites were found in both the virulent field isolates and the attenuated vaccine strains. In addition, during the attenuation process, sequence analyses showed changes in the pattern of the parasite subpopulations. Despite high polymorphism found by sequence analyses, the patterns observed and the number of repeats, order, or motifs found could not discriminate between virulent field isolates and attenuated vaccine strains of the parasite. PMID- 22075978 TI - The effect of clotrimazole on energy substrate uptake and carcinogenesis in intestinal epithelial cells. AB - Clotrimazole has anticarcinogenic activity in several cell types. Our aims were to investigate the anticarcinogenic effect of clotrimazole in a tumoral intestinal epithelial (Caco-2) cell line, to compare it with the effect in a nontumoral intestinal epithelial cell line (IEC-6 cells), and to investigate inhibition of energy substrate uptake as a mechanism contributing to it. The effect of clotrimazole on cell proliferation, viability and differentiation, H deoxyglucose (H-DG), H-O-methyl-glucose (H-OMG), and C-butyrate uptake, as well as mRNA expression levels of glucose transporters was assessed. In Caco-2 cells, clotrimazole decreased cellular viability and proliferation and increased cell differentiation. The effect on cell proliferation and viability was potentiated by rhodamine123. Clotrimazole also decreased cellular viability and proliferation in IEC-6 cells, but increased the cellular DNA synthesis rate and had no effect on cell differentiation. Exposure of Caco-2 cells to clotrimazole (10 umol/l) for 1 and 7 days increased (by 20-30%) the uptake of H-DG and H-OMG, respectively, but had no effect on C-butyrate uptake. The effect on H-DG and H-OMG transport was maximal at 10 umol/l, and the pharmacological characteristics of transport were not changed. However, clotrimazole changed the mRNA expression levels of the facilitative glucose transporter 2 and the Na-dependent glucose cotransporter. Clotrimazole exhibits comparable cytotoxic effects in tumoral and nontumoral intestinal epithelial cell lines. In Caco-2 cells, the cytotoxic effect of clotrimazole was strongly potentiated by the inhibition of oxidative phosphorylation. Moreover, stimulation of glucose uptake might be a compensation mechanism in response to the glycolysis inhibition caused by clotrimazole. PMID- 22075979 TI - Vascular endothelial growth factor receptor 2 inhibition in-vivo affects tumor vasculature in a tumor type-dependent way and downregulates vascular endothelial growth factor receptor 2 protein without a prominent role for miR-296. AB - The precise molecular effects that antiangiogenic drugs exert on tumor vasculature remain to be poorly understood. We therefore set out to investigate the molecular and architectural changes that occur in the vasculature of two different tumor types that both respond to vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor therapy. Mice bearing Lewis lung carcinoma (LLC) or B16.F10 melanoma were treated with vandetanib (ZD6474), a VEGFR2/epidermal growth factor receptor (EGFR)/REarranged during Transfection (RET) kinase inhibitor, resulting in a significant 80% reduction in tumor outgrowth. Although in LLC the vascular density was not affected by vandetanib treatment, it was significantly decreased in B16.F10. In LLC, vandetanib treatment induced a shift in vascular gene expression toward stabilization, as demonstrated by upregulation of Tie2 and N-cadherin and downregulation of Ang2 and integrin beta3. In contrast, only eNOS and P-selectin responded to vandetanib treatment in B16.F10 vasculature. Strikingly, vandetanib reduced protein expression of VEGFR2 in both models, whereas mRNA remained unaffected. Analysis of miR-296 expression allowed us to exclude a role for the recently proposed microRNA-296 in VEGFR2 posttranslational control in LLC and B16.F10 in vivo. Our data demonstrate that VEGFR2/EGFR inhibition through vandetanib slows down both LLC and B16.F10 tumor growth. Yet, the underlying molecular changes in the vasculature that orchestrate the antitumor effect differ between tumor types. Importantly, in both models, vandetanib treatment induced loss of its pharmacological target, which was not directly related to miR-296 expression. Validation of our observations in tumor biopsies from VEGFR2 inhibitor-treated patients will be essential to unravel the effects of VEGFR2 inhibitor therapy on tumor vasculature in relation to therapeutic efficacy. PMID- 22075980 TI - Inhibitory effect of Trolox on the migration and invasion of human lung and cervical cancer cells. AB - The antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) is implicated in migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of Trolox on metastatic cancer cells is not known. We found that a non-cytotoxic dose of Trolox decreased phorbol 12 myristate 13-acetate (PMA)-induced invasion and migration of both A549 and HeLa cancer cells. We also found that Trolox suppressed both the expression and the proteolytic activity of matrix metalloproteinase-9 (MMP-9), and that the promoter activity of PMA-induced MMP-9 was inhibited by Trolox. Our results show that Trolox inhibits the transcriptional activity of MMP-9 by suppression of NF-kappaB transactivation. These results indicate that Trolox inhibits NF-kappaB-mediated MMP-9 expression, leading to the suppression of migration and invasion in lung and cervical cancer cells. Trolox is a potential agent for clinical use in preventing the invasion and metastasis of human malignant lung and cervical cancers. PMID- 22075981 TI - An infected urachal cyst--a rare diagnosis in a child with acute abdominal pain. AB - A 2-year-old girl who presented with acute abdominal pain and spiking fever was diagnosed with an infected urachal cyst. Ultrasonography aided the diagnosis and the urachal remnant was removed successfully through a single laparoscopic procedure. Treatment is through removal of the complete structure, to prevent malignant degeneration in adulthood. CONCLUSION: Urachal cysts may cause abdominal complaints when infected. Although rare, they should be added to the differential diagnosis of acute abdominal pain in the paediatric patient, as this case illustrates. PMID- 22075982 TI - Diverse p63 and p73 isoforms regulate Delta133p53 expression through modulation of the internal TP53 promoter activity. AB - In response to stress, p53 binds and transactivates the internal TP53 promoter, thus regulating the expression of its own isoform, Delta133p53alpha. Here, we report that, in addition to p53, at least four p63/p73 isoforms regulate Delta133p53 expression at transcriptional level: p63beta, DeltaNp63alpha, DeltaNp63beta and DeltaNp73gamma. This regulation occurs through direct DNA binding to the internal TP53 promoter as demonstrated by chromatin immunoprecipitation and the use of DNA-binding mutant p63. The promoter regions involved in the p63/p73-mediated transactivation were identified using deleted, mutant and polymorphic luciferase reporter constructs. In addition, we observed that transient expression of p53 family members modulates endogenous Delta133p53alpha expression at both mRNA and protein levels. We also report concomitant variation of p63 and Delta133p53 expression during keratinocyte differentiation of HaCat cells and induced pluripotent stem cells derived from mutated p63 ectodermal dysplasia patients. Finally, proliferation assays indicated that Delta133p53alpha isoform regulates the anti-proliferative activities of p63beta, DeltaNp63alpha, DeltaNp63beta and DeltaNp73gamma. Overall, this study shows a strong interplay between p53, p63 and p73 isoforms to orchestrate cell fate outcome. PMID- 22075983 TI - BCL2A1: the underdog in the BCL2 family. AB - B-cell lymphoma 2 (BCL2) proteins are important cell death regulators, whose main function is to control the release of cytochrome c from mitochondria in the intrinsic apoptotic pathway. They comprise both pro- and anti-apoptotic proteins, which interact in various ways to induce or prevent pore formation in the outer mitochondrial membrane. Due to their central function in the apoptotic machinery, BCL2 proteins are often deregulated in cancer. To this end, many anti-apoptotic BCL2 proteins have been identified as important cellular oncogenes and attractive targets for anti-cancer therapy. In this review, the existing knowledge on B-cell lymphoma 2-related protein A1 (BCL2A1)/Bcl-2-related gene expressed in fetal liver (Bfl-1), one of the less extensively studied anti-apoptotic BCL2 proteins, is summarized. BCL2A1 is a highly regulated nuclear factor kappaB (NF-kappaB) target gene that exerts important pro-survival functions. In a physiological context, BCL2A1 is mainly expressed in the hematopoietic system, where it facilitates survival of selected leukocytes subsets and inflammation. However, BCL2A1 is overexpressed in a variety of cancer cells, including hematological malignancies and solid tumors, and may contribute to tumor progression. Therefore, the development of small molecule inhibitors of BCL2A1 may be a promising approach mainly to sensitize tumor cells for apoptosis and thus improve the efficiency of anti-cancer therapy. PMID- 22075984 TI - Nucleoporin NUP153 guards genome integrity by promoting nuclear import of 53BP1. AB - 53BP1 is a mediator of DNA damage response (DDR) and a tumor suppressor whose accumulation on damaged chromatin promotes DNA repair and enhances DDR signaling. Using foci formation of 53BP1 as a readout in two human cell lines, we performed an siRNA-based functional high-content microscopy screen for modulators of cellular response to ionizing radiation (IR). Here, we provide the complete results of this screen as an information resource, and validate and functionally characterize one of the identified 'hits': a nuclear pore component NUP153 as a novel factor specifically required for 53BP1 nuclear import. Using a range of cell and molecular biology approaches including live-cell imaging, we show that knockdown of NUP153 prevents 53BP1, but not several other DDR factors, from entering the nuclei in the newly forming daughter cells. This translates into decreased IR-induced 53BP1 focus formation, delayed DNA repair and impaired cell survival after IR. In addition, NUP153 depletion exacerbates DNA damage caused by replication stress. Finally, we show that the C-terminal part of NUP153 is required for effective 53BP1 nuclear import, and that 53BP1 is imported to the nucleus through the NUP153-importin-beta interplay. Our data define the structure function relationships within this emerging 53BP1-NUP153/importin-beta pathway and implicate this mechanism in the maintenance of genome integrity. PMID- 22075985 TI - Many stimuli pull the necrotic trigger, an overview. AB - The lab of Jurg Tschopp was the first to report on the crucial role of receptor interacting protein kinase 1 (RIPK1) in caspase-independent cell death. Because of this pioneer finding, regulated necrosis and in particular RIPK1/RIPK3 kinase mediated necrosis, referred to as necroptosis, has become an intensively studied form of regulated cell death. Although necrosis was identified initially as a backup cell death program when apoptosis is blocked, it is now recognized as a cellular defense mechanism against viral infections and as being critically involved in ischemia-reperfusion damage. The observation that RIPK3 ablation rescues embryonic lethality in mice deficient in caspase-8 or Fas-associated protein-via-a-death-domain demonstrates the crucial role of this apoptotic platform in the negative control of necroptosis during development. Here, we review and discuss commonalities and differences of the increasing list of inducers of regulated necrosis ranging from cytokines, pathogen-associated molecular patterns, to several forms of physicochemical cellular stress. Since the discovery of the crucial role of RIPK1 and RIPK3 in necroptosis, these kinases have become potential therapeutic targets. The availability of new pharmacological inhibitors and transgenic models will allow us to further document the important role of this form of cell death in degenerative, inflammatory and infectious diseases. PMID- 22075986 TI - The inflammasome: in memory of Dr. Jurg Tschopp. AB - A decade ago, Jurg Tschopp introduced the concept of the inflammasome. This exciting discovery of a macromolecular complex that senses 'danger' and initiates the inflammatory response contributed to a renaissance in the fields of innate immunity and cell death. Jurg led the biochemical characterization of the inflammasome complex and demonstrated that spontaneous hyperactivation of this interleukin (IL)-1beta processing machinery is the molecular basis of a spectrum of hereditary periodic fever syndromes, caused by mutated forms of the inflammasome scaffolding receptor, NLRP3. The identification of the underlying mechanism in these disorders has led to their now successful therapy, with the use of the IL-1 receptor antagonist in the clinic. Jurg's pioneering work has subsequently defined a number of inflammasome agonists ranging from microbial molecules expressed during infection, to triggers of sterile inflammation, most notably gout-associated uric acid crystals, asbestos, silica and nanoparticles. More recently, Jurg introduced the critical new concept of the metabolic inflammasome, which senses metabolic stress and contributes to the onset of the metabolic syndrome associated with obesity and type 2 diabetes. Jurg was an outstanding and skillful biochemist, an elegant and rigorous researcher often far ahead of his peers. He was a truly amiable person, fair, generous and inspiring, and will be most remembered for his infectious enthusiasm. We write this review article on the inflammasome in his honor and dedicate it to his memory. PMID- 22075987 TI - Caspase-2: the orphan caspase. AB - Despite an abundance of literature on the role of caspase-2 in apoptosis, there exists much controversy about this protease making it difficult to place caspase 2 correctly in the apoptotic cascade, and hence its role in apoptosis remains unclear. The identification of the PIDDosome as a signaling platform for caspase 2 activation prompted intense investigation into the true role of this orphan caspase. What has emerged is the idea that caspase-2 may not be mandatory for apoptosis and that activation of this caspase in response to some forms of stress has other effects on the cell such as regulation of cell cycle progression. This idea is particularly relevent to the discovery that caspase-2 may act as a tumor suppressor. Here, we discuss the proposed mechanisms through which caspase-2 signals, in particular those involving PIDD, and their impact on cellular fate. PMID- 22075988 TI - Regulation of CD95/Fas signaling at the DISC. AB - CD95 (APO-1/Fas) is a member of the death receptor (DR) family. Stimulation of CD95 leads to induction of apoptotic and non-apoptotic signaling pathways. The formation of the CD95 death-inducing signaling complex (DISC) is the initial step of CD95 signaling. Activation of procaspase-8 at the DISC leads to the induction of DR-mediated apoptosis. The activation of procaspase-8 is blocked by cellular FLICE-inhibitory proteins (c-FLIP). This review is focused on the role in the CD95-mediated signaling of the death effector domain-containing proteins procaspase-8 and c-FLIP. We discuss how dynamic cross-talk between procaspase-8 and c-FLIP at the DISC regulates life/death decisions at CD95. PMID- 22075989 TI - A supramolecular assembly formed by influenza A virus genomic RNA segments. AB - The influenza A virus genome consists of eight viral RNAs (vRNAs) that form viral ribonucleoproteins (vRNPs). Even though evidence supporting segment-specific packaging of vRNAs is accumulating, the mechanism ensuring selective packaging of one copy of each vRNA into the viral particles remains largely unknown. We used electron tomography to show that the eight vRNPs emerge from a common 'transition zone' located underneath the matrix layer at the budding tip of the virions, where they appear to be interconnected and often form a star-like structure. This zone appears as a platform in 3D surface rendering and is thick enough to contain all known packaging signals. In vitro, all vRNA segments are involved in a single network of intermolecular interactions. The regions involved in the strongest interactions were identified and correspond to known packaging signals. A limited set of nucleotides in the 5' region of vRNA 7 was shown to interact with vRNA 6 and to be crucial for packaging of the former vRNA. Collectively, our findings support a model in which the eight genomic RNA segments are selected and packaged as an organized supramolecular complex held together by direct base pairing of the packaging signals. PMID- 22075990 TI - The Mouse Genome Database (MGD): comprehensive resource for genetics and genomics of the laboratory mouse. AB - The Mouse Genome Database (MGD, http://www.informatics.jax.org) is the international community resource for integrated genetic, genomic and biological data about the laboratory mouse. Data in MGD are obtained through loads from major data providers and experimental consortia, electronic submissions from laboratories and from the biomedical literature. MGD maintains a comprehensive, unified, non-redundant catalog of mouse genome features generated by distilling gene predictions from NCBI, Ensembl and VEGA. MGD serves as the authoritative source for the nomenclature of mouse genes, mutations, alleles and strains. MGD is the primary source for evidence-supported functional annotations for mouse genes and gene products using the Gene Ontology (GO). MGD provides full annotation of phenotypes and human disease associations for mouse models (genotypes) using terms from the Mammalian Phenotype Ontology and disease names from the Online Mendelian Inheritance in Man (OMIM) resource. MGD is freely accessible online through our website, where users can browse and search interactively, access data in bulk using Batch Query or BioMart, download data files or use our web services Application Programming Interface (API). Improvements to MGD include expanded genome feature classifications, inclusion of new mutant allele sets and phenotype associations and extensions of GO to include new relationships and a new stream of annotations via phylogenetic-based approaches. PMID- 22075991 TI - The Gene Wiki in 2011: community intelligence applied to human gene annotation. AB - The Gene Wiki is an open-access and openly editable collection of Wikipedia articles about human genes. Initiated in 2008, it has grown to include articles about more than 10,000 genes that, collectively, contain more than 1.4 million words of gene-centric text with extensive citations back to the primary scientific literature. This growing body of useful, gene-centric content is the result of the work of thousands of individuals throughout the scientific community. Here, we describe recent improvements to the automated system that keeps the structured data presented on Gene Wiki articles in sync with the data from trusted primary databases. We also describe the expanding contents, editors and users of the Gene Wiki. Finally, we introduce a new automated system, called WikiTrust, which can effectively compute the quality of Wikipedia articles, including Gene Wiki articles, at the word level. All articles in the Gene Wiki can be freely accessed and edited at Wikipedia, and additional links and information can be found at the project's Wikipedia portal page: http://en.wikipedia.org/wiki/Portal:Gene_Wiki. PMID- 22075992 TI - OGEE: an online gene essentiality database. AB - OGEE is an Online GEne Essentiality database. Its main purpose is to enhance our understanding of the essentiality of genes. This is achieved by collecting not only experimentally tested essential and non-essential genes, but also associated gene features such as expression profiles, duplication status, conservation across species, evolutionary origins and involvement in embryonic development. We focus on large-scale experiments and complement our data with text-mining results. Genes are organized into data sets according to their sources. Genes with variable essentiality status across data sets are tagged as conditionally essential, highlighting the complex interplay between gene functions and environments. Linked tools allow the user to compare gene essentiality among different gene groups, or compare features of essential genes to non-essential genes, and visualize the results. OGEE is freely available at http://ogeedb.embl.de. PMID- 22075993 TI - Synthetic transactivation screening reveals ETV4 as broad coactivator of hypoxia inducible factor signaling. AB - The human prolyl-4-hydroxylase domain (PHD) proteins 1-3 are known as cellular oxygen sensors, acting via the degradation of hypoxia-inducible factor (HIF) alpha-subunits. PHD2 and PHD3 genes are inducible by HIFs themselves, suggesting a negative feedback loop that involves PHD abundance. To identify novel regulators of the PHD2 gene, an expression array of 704 transcription factors was screened by a method that allows distinguishing between HIF-dependent and HIF independent promoter regulation. Among others, the E-twenty six transcription factor ETS translocation variant 4 (ETV4) was found to contribute to PHD2 gene expression particularly under hypoxic conditions. Mechanistically, complex formation between ETV4 and HIF-1/2alpha was observed by mammalian two-hybrid and fluorescence resonance energy transfer analysis. HIF-1alpha domain mapping, CITED2 overexpression and factor inhibiting HIF depletion experiments provided evidence for cooperation between HIF-1alpha and p300/CBP in ETV4 binding. Chromatin immunoprecipitation confirmed ETV4 and HIF-1alpha corecruitment to the PHD2 promoter. Of 608 hypoxically induced transcripts found by genome-wide expression profiling, 7.7% required ETV4 for efficient hypoxic induction, suggesting a broad role of ETV4 in hypoxic gene regulation. Endogenous ETV4 highly correlated with PHD2, HIF-1/2alpha and several established markers of tissue hypoxia in 282 human breast cancer tissue samples, corroborating a functional interplay between the ETV4 and HIF pathways. PMID- 22075994 TI - Functional and direct interaction between the RNA binding protein HuD and active Akt1. AB - The RNA binding protein HuD plays essential roles in neuronal development and plasticity. We have previously shown that HuD stimulates translation. Key for this enhancer function is the linker region and the poly(A) binding domain of HuD that are also critical for its function in neurite outgrowth. Here, we further explored the underlying molecular interactions and found that HuD but not the ubiquitously expressed HuR interacts directly with active Akt1. We identify that the linker region of HuD is required for this interaction. We also show by using chimeric mutants of HuD and HuR, which contain the reciprocal linker between RNA binding domain 2 (RBD2) and RBD3, respectively, and by overexpressing a dominant negative mutant of Akt1 that the HuD-Akt1 interaction is functionally important, as it is required for the induction of neurite outgrowth in PC12 cells. These results suggest the model whereby RNA-bound HuD functions as an adapter to recruit Akt1 to trigger neurite outgrowth. These data might also help to explain how HuD enhances translation of mRNAs that encode proteins involved in neuronal development. PMID- 22075995 TI - Self-assembled nucleolipids: from supramolecular structure to soft nucleic acid and drug delivery devices. AB - This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly. High-resolution structural investigations reveal the diversity and complexity of assemblies formed by these bioinspired amphiphiles, resulting from the interplay between aggregation of the lipid chains and base-base interactions. Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids. Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs. PMID- 22075996 TI - SNPeffect 4.0: on-line prediction of molecular and structural effects of protein coding variants. AB - Single nucleotide variants (SNVs) are, together with copy number variation, the primary source of variation in the human genome and are associated with phenotypic variation such as altered response to drug treatment and susceptibility to disease. Linking structural effects of non-synonymous SNVs to functional outcomes is a major issue in structural bioinformatics. The SNPeffect database (http://snpeffect.switchlab.org) uses sequence- and structure-based bioinformatics tools to predict the effect of protein-coding SNVs on the structural phenotype of proteins. It integrates aggregation prediction (TANGO), amyloid prediction (WALTZ), chaperone-binding prediction (LIMBO) and protein stability analysis (FoldX) for structural phenotyping. Additionally, SNPeffect holds information on affected catalytic sites and a number of post-translational modifications. The database contains all known human protein variants from UniProt, but users can now also submit custom protein variants for a SNPeffect analysis, including automated structure modeling. The new meta-analysis application allows plotting correlations between phenotypic features for a user selected set of variants. PMID- 22075997 TI - STITCH 3: zooming in on protein-chemical interactions. AB - To facilitate the study of interactions between proteins and chemicals, we have created STITCH, an aggregated database of interactions connecting over 300,000 chemicals and 2.6 million proteins from 1133 organisms. Compared to the previous version, the number of chemicals with interactions and the number of high confidence interactions both increase 4-fold. The database can be accessed interactively through a web interface, displaying interactions in an integrated network view. It is also available for computational studies through downloadable files and an API. As an extension in the current version, we offer the option to switch between two levels of detail, namely whether stereoisomers of a given compound are shown as a merged entity or as separate entities. Separate display of stereoisomers is necessary, for example, for carbohydrates and chiral drugs. Combining the isomers increases the coverage, as interaction databases and publications found through text mining will often refer to compounds without specifying the stereoisomer. The database is accessible at http://stitch.embl.de/. PMID- 22075998 TI - ENCODE whole-genome data in the UCSC Genome Browser: update 2012. AB - The Encyclopedia of DNA Elements (ENCODE) Consortium is entering its 5th year of production-level effort generating high-quality whole-genome functional annotations of the human genome. The past year has brought the ENCODE compendium of functional elements to critical mass, with a diverse set of 27 biochemical assays now covering 200 distinct human cell types. Within the mouse genome, which has been under study by ENCODE groups for the past 2 years, 37 cell types have been assayed. Over 2000 individual experiments have been completed and submitted to the Data Coordination Center for public use. UCSC makes this data available on the quality-reviewed public Genome Browser (http://genome.ucsc.edu) and on an early-access Preview Browser (http://genome-preview.ucsc.edu). Visual browsing, data mining and download of raw and processed data files are all supported. An ENCODE portal (http://encodeproject.org) provides specialized tools and information about the ENCODE data sets. PMID- 22075999 TI - Response of blood pressure and blood glucose to treatment with recombinant tissue type plasminogen activator in acute ischemic stroke: evidence from the virtual international stroke trials archive. AB - BACKGROUND AND PURPOSE: Elevations in blood pressure (BP) and blood glucose are common during stroke and may represent a stress response secondary to the acute neurological deficit. If so, they should settle more completely in recombinant tissue-type plasminogen activator (rtPA)-treated patients in association with improved neurological status. METHODS: We performed a controlled comparison of 24 hour declines in BP and glucose in rtPA-treated and control patients from the Virtual Stroke International Stroke Trial Archive (VISTA) database. Twenty-four hour falls in BP and glucose were compared using multiple regression to account for baseline imbalances. The logarithmic transformation of glucose was used and 24-hour differences expressed as ratios of 24 hours to admission geometric means. Two-way analysis of variance was used to test for interaction between rtPA and early improvement for 24-hour falls in BP and blood glucose. RESULTS: BP analysis included 5406 patients (rtPA=41%) and glucose analysis 4288 (rtPA=37%). rtPA treated patients were younger, less likely to have a history of hypertension or diabetes, and had more severe strokes on admission. BP and glucose were lower at baseline in rtPA-treated patients than control subjects. On regression, rtPA predicted significantly greater 24-hour falls in systolic BP (beta=3.9; 95% CI, 2.8-5.0), diastolic BP (beta=3.1; 95% CI, 2.4-3.9), and glucose (beta=0.97; 95% CI, 0.95-0.99). rtPA did not interact with early neurological improvement for 24 hour falls in systolic BP (P=0.72), diastolic BP (P=0.79), or blood glucose (P=0.51). CONCLUSIONS: A stress response does not appear to be the principal cause of elevations in BP and glucose during stroke. PMID- 22076001 TI - Aortic stiffness predicts functional outcome in patients after ischemic stroke. AB - BACKGROUND AND PURPOSE: Increased aortic stiffness (measured by carotid-femoral pulse wave velocity) and central augmentation index have been shown to independently predict cardiovascular events, including stroke. We studied whether pulse wave velocity and central augmentation index predict functional outcome after ischemic stroke. METHODS: In a prospective study, we enrolled 99 patients with acute ischemic stroke (age 63.7 +/- 12.4 years, admission National Institutes of Health Stroke Scale score 6.6 +/- 6.6, mean +/- SD). Carotid femoral pulse wave velocity and central augmentation index (SphygmoCor) were measured 1 week after stroke onset. Functional outcome was evaluated 90 days after stroke using the modified Rankin Scale with modified Rankin Scale score of 0 to 1 considered an excellent outcome. RESULTS: In univariate analysis, low carotid-femoral pulse wave velocity (P=0.000001) and low central augmentation index (P=0.028) were significantly associated with excellent stroke outcome. Age, severity of stroke, presence of previous stroke, diabetes, heart rate, and peripheral pressures also predicted stroke functional outcome. In multivariate analysis, the predictive value of carotid-femoral pulse wave velocity (<9.4 m/s) remained significant (OR, 0.21; 95% CI, 0.06-0.79; P=0.02) after adjustment for age, National Institutes of Health Stroke Scale score on admission, and presence of previous stroke. By contrast, central augmentation index had no significant predictive value after adjustment. CONCLUSIONS: This study indicates that aortic stiffness is an independent predictor of functional outcome in patients with acute ischemic stroke. PMID- 22076000 TI - Concurrent validity and reliability of retrospective scoring of the Pediatric National Institutes of Health Stroke Scale. AB - BACKGROUND AND PURPOSE: The Pediatric National Institutes of Health Stroke Scale (PedNIHSS), an adaptation of the adult National Institutes of Health Stroke Scale, is a quantitative measure of stroke severity shown to be reliable when scored prospectively. The ability to calculate the PedNIHSS score retrospectively would be invaluable in the conduct of observational pediatric stroke studies. The study objective was to assess the concurrent validity and reliability of estimating the PedNIHSS score retrospectively from medical records. METHODS: Neurological examinations from medical records of 75 children enrolled in a prospective PedNIHSS validation study were photocopied. Four neurologists of varying training levels blinded to the prospective PedNIHSS scores reviewed the records and retrospectively assigned PedNIHSS scores. Retrospective scores were compared among raters and to the prospective scores. RESULTS: Total retrospective PedNIHSS scores correlated highly with total prospective scores (R(2)=0.76). Interrater reliability for the total scores was "excellent" (intraclass correlation coefficient, 0.95; 95% CI, 0.94-0.97). Interrater reliability for individual test items was "substantial" or "excellent" for 14 of 15 items. CONCLUSIONS: The PedNIHSS score can be scored retrospectively from medical records with a high degree of concurrent validity and reliability. This tool can be used to improve the quality of retrospective pediatric stroke studies. PMID- 22076002 TI - Activation of signal transducer and activator of transcription-3 by a peroxisome proliferator-activated receptor gamma agonist contributes to neuroprotection in the peri-infarct region after ischemia in oophorectomized rats. AB - BACKGROUND AND PURPOSE: The role of the phosphorylated signal transducer and activator of transcription-3 (p-STAT3) after cerebral ischemia by the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone (PGZ) remains controversial. Whether the increase in p-STAT3 by estrogen is mediated by the estrogen receptor alpha is also obscure. We examined the role of p-STAT3, PPARgamma, and estrogen receptor alpha against ischemic brain damage after PGZ treatment. METHODS: Female Wistar rats subjected or not subjected to bilateral oophorectomy were injected with 1.0 or 2.5 mg/kg PGZ 2 days, 1 day, and 1 hour before 90-minute middle cerebral artery occlusion-reperfusion and compared with vehicle-control rats. RESULTS: The cortical infarct size was larger in ovariectomized than in nonovarietomized rats; it was reduced by PGZ treatment. Inversely with the reduction of the infarct size, PPARgamma, and p-STAT3 but not estrogen receptor alpha in the peri-infarct area were increased in PGZ-treated compared with vehicle-control rats. The increase in PPARgamma and p-STAT3 was associated with the transactivation of antiapoptotic and survival genes and the reduction of caspase-3 in this area. Inhibitors of PPARgamma or STAT3 abolished the PGZ-induced neuroprotection and the increase in p-STAT3. More importantly, p STAT3 increased by PGZ was bound to PPARgamma and the complex translocated to the nucleus to dock to the response element through p-STAT3. CONCLUSIONS: Our findings suggest that the activation in the peri-infarct region of p-STAT3 and PPARgamma by PGZ is essential for neuroprotection after ischemia and that PGZ may be of benefit even in postmenopausal stroke patients. PMID- 22076003 TI - Low-molecular-weight heparin in atherosclerotic stroke: a surprising resurrection of anticoagulants? PMID- 22076004 TI - Low-molecular-weight heparin versus aspirin for acute ischemic stroke with large artery occlusive disease: subgroup analyses from the Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study. AB - BACKGROUND AND PURPOSE: The Fraxiparin in Stroke Study for the treatment of ischemic stroke (FISS-tris) study showed no superiority of low-molecular-weight heparin (LMWH) over aspirin for the primary end point (Barthel Index) in acute ischemic stroke due to large artery occlusive disease. This study aims to evaluate the efficacy of LMWH and aspirin in selected subgroups so as to generate hypotheses for further studies. METHODS: The FISS-tris study was a multicenter, randomized trial to investigate the efficacy and safety of LMWH (nadroparin calcium 3800 antifactor Xa IU/0.4 mL subcutaneously twice daily) or aspirin (160 mg once daily) for the treatment of patients with acute ischemic stroke and large artery occlusive disease. The primary outcome was the Barthel Index score dichotomized at 85 6 months poststroke. Exploratory subgroup analysis was performed using different levels of baseline characteristics and the distribution of symptomatic arteries. RESULTS: Compared with aspirin, LMWH improved outcome among older patients >68 years (P=0.043; OR, 1.86; 95% CI, 1.02-3.41) without ongoing antiplatelet treatment on admission (P=0.029; OR, 1.85; 95% CI, 1.06 3.21) and with symptomatic posterior circulation arterial disease (P=0.001; OR, 5.76; 95% CI, 2.00-16.56). CONCLUSIONS: Our findings suggest that LMWH may be of benefit in certain subgroups of patients with acute cerebral infarct and large artery occlusive disease. Hence, further investigation of LMWH may be justified in subgroups such as the elderly, nonusers of antiplatelet agents, and patients with posterior circulation stenosis. CLINICAL TRIAL REGISTRATION: URL: www.strokecenter.org/trials. Unique identifier: registration no. 493. PMID- 22076005 TI - Moderate dietary restriction reduces p53-mediated neurovascular damage and microglia activation after hypoxic ischemia in neonatal brain. AB - BACKGROUND AND PURPOSE: Neurovascular damage, including neuronal apoptosis and blood-brain barrier (BBB) damage, and microglia activation account for the hypoxic-ischemia (HI) susceptibility in neonatal brain. The p53 upregulation is involved in apoptosis, endothelial cell damage, and microglia activation. We hypothesized that underweight induced by dietary restriction (DR) protects against HI in rat pups by attenuating p53-mediated neurovascular damage. METHODS: Male rat pups were grouped as normal litter (NL) size (12 pups/dam), DR (18 pups/dam), and extreme DR (24 pups/dam) from postnatal day 1 and subjected to HI on postnatal day 7. Immunohistochemistry and immunoblotting were used to determine p53, phospho-murine double minute-2, caspases, BBB damage and microglia activation, and immunofluorescence to determine the cellular distribution of p53. Pharmacological approaches were used to regulate p53. RESULTS: The NL, DR, and extreme DR pups had similar TUNEL-positive cells and caspases on postnatal day 7 and comparable learning performance at adulthood. After HI, the DR-HI, but not extreme DR-HI, pups had significantly lower p53, higher phospho-murine double minute-2, lower cleaved caspases, less BBB damage and microglia activation, and less brain volume loss than NL-HI pups. In NL-HI pups, p53 expression was located mainly in the neurons, endothelial cells, and microglia. The p53 blockage by pifithrin-alpha in NL-HI pups decreased apoptosis, BBB damage, and microglia activation, and was neuroprotective. In contrast, upregulating p53 by nutlin-3 in DR-HI pups increased apoptosis, BBB damage, and microglia activation, and worsened brain damage. CONCLUSIONS: Moderate DR, but not extreme DR, reduces p53 mediated neurovascular damage after HI and confers long-term protection in neonatal brain. PMID- 22076006 TI - Plasmalemma permeability and necrotic cell death phenotypes after intracerebral hemorrhage in mice. AB - BACKGROUND AND PURPOSE: Traumatic and ischemic brain injury induce plasmalemma permeability and necrosis; however, no studies have examined these aspects of cellular injury in intracerebral hemorrhage models. METHODS: In vivo propidium iodide (PI) and YOYO-1 were used to assess plasmalemma damage after collagenase induced intracerebral hemorrhage in mice. Ex vivo aspartylglutamylvalylaspartic acid, terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, and electron microscopy were used to assess the relationship between plasmalemma permeability and mode of cell death. Cell types vulnerable to plasmalemma damage were determined by immunohistochemistry. RESULTS: Plasmalemma permeability was first detected in the lesion at 1 to 3 hours and peaked at 48 to 72 hours. Neurons and IBA-1-positive cells with morphological features of monocytes were sensitive, whereas resident microglia and astrocytes were resistant to plasmalemma permeability. PI+ cells colocalized with fluorescent-labeled caspase substrates and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling beginning at 3 to 6 hours. At 48 hours, greater than half of injured cells were PI+/aspartylglutamylvalylaspartic acid- or PI+/terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling- suggesting necrosis, and <5% were PI-/terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling+ or PI-/aspartylglutamylvalylaspartic acid+. Electron microscopy confirmed ultrastructural features of necrosis at 24 hours after intracerebral hemorrhage, high mobility group box protein-1 was released from permeable cells, and mice deficient in receptor interacting protein kinase (RIPK) 3, a known necrosis trigger, had 50% less PI+ cells at 24 hours. Permeable cells remained in the brain for at least 24 hours with <10% spontaneous resealing. CONCLUSIONS: Necrosis contributes to cell demise after intracerebral hemorrhage. Programmed necrosis and plasmalemma damage may represent novel therapeutic targets to prevent cell death or rescue injured cells after intracerebral hemorrhage. PMID- 22076008 TI - Relative survival after transient ischaemic attack: results from the Program of Research Informing Stroke Management (PRISM) study. AB - BACKGROUND AND PURPOSE: There is a lack of modern-day data quantifying the effect of transient ischemic attack (TIA) on survival, and recent data do not take into account expected survival. METHODS: Data for 22 157 adults hospitalized with a TIA from July 1, 2000, to June 30, 2007, in New South Wales, Australia, were linked with registered deaths to June 30, 2009. We estimated survival relative to the age- and sex-matched general population up to 9-years after hospitalization for TIA comparing relative risk of excess death between selected subgroups. RESULTS: At 1 year, 91.5% of hospitalized patients with TIA survived compared with 95.0% expected survival in the general population. After 5 years, observed survival was 13.2% lower than expected in relative terms. By 9 years, observed survival was 20% lower than expected. Females had higher relative survival than males (relative risk, 0.79; 95% CI, 0.69-0.90; P<0.001). Increasing age was associated with an increasing risk of excess death compared with the age-matched population. Prior hospitalization for stroke (relative risk, 2.63; 95% CI, 1.98 3.49) but not TIA (relative risk, 1.42; 95% CI, 0.86-2.35) significantly increased the risk of excess death. Of all risk factors assessed, congestive heart failure, atrial fibrillation, and prior hospitalization for stroke most strongly impacted survival. CONCLUSIONS: This study is the first to quantify the long-term effect of hospitalized TIA on relative survival according to age, sex, and medical history. TIA reduces survival by 4% in the first year and by 20% within 9 years. TIA has a minimal effect on mortality in patients <50 years but heralds significant reduction in life expectancy in those >65 years. PMID- 22076009 TI - Acute hemodynamic disturbances during lumbar spine surgery. PMID- 22076007 TI - Differential susceptibility to axonopathy in necrotic and non-necrotic perinatal white matter injury. AB - BACKGROUND AND PURPOSE: White matter injury (WMI) is the leading cause of brain injury in preterm survivors and results in myelination failure. Although axonal degeneration occurs in necrotic lesions, the role of axonopathy in myelination failure remains controversial for diffuse non-necrotic WMI, which is currently the major form of WMI. We determined the burden of axonopathy in diffuse lesions. METHODS: We analyzed WMI in a preterm fetal sheep model of global cerebral ischemia that replicates the relative burden of necrotic and non-necrotic human WMI. WMI was analyzed at 1 or 2 weeks after ischemia and identified by ex vivo high-field (11.7 Tesla) magnetic resonance imaging of fixed brain tissue. Axonal integrity was analyzed by immunohistochemical detection of axon injury markers and by transmission electron microscopy to quantify axon loss and degeneration in magnetic resonance imaging-defined lesions. RESULTS: Axonal degeneration, defined by staining for neurofilament protein and beta-amyloid precursor protein, was restricted to discrete necrotic foci with robust microglial activation. Unexpectedly, axonal degeneration was not visualized in the major form of WMI, which comprised large non-necrotic lesions with diffuse reactive astrogliosis. In these major lesions, quantitative electron microscopy studies confirmed no significant differences in the density of intact and degenerating axons or in the distribution of axon diameters relative to controls. CONCLUSIONS: The mechanism of myelination failure differs significantly in perinatal WMI dependent on the burden of necrosis. Axonopathy is associated with focal necrotic injury but not with primary diffuse non-necrotic lesions, which supports that intact axons in the primary lesions are potential targets for myelination. PMID- 22076010 TI - A bridge too far. PMID- 22076011 TI - Risk stratification schemes, anticoagulation use and outcomes: the risk- treatment paradox in patients with newly diagnosed non-valvular atrial fibrillation. AB - OBJECTIVE: To examine whether warfarin use and outcomes differ across CHADS(2) and CHA(2)DS(2)-VASc risk strata for non-valvular atrial fibrillation (NVAF). DESIGN: Population-based cohort study using linked administrative databases in Alberta, Canada. SETTING: Inpatient and outpatient. PATIENTS: 42,834 consecutive patients >= 20 years of age with newly diagnosed NVAF. MAIN OUTCOME MEASURES: Cerebrovascular events and/or mortality in the first year after diagnosis. RESULTS: Of 42,834 NVAF patients, 22.7% were low risk on the CHADS(2) risk score (0), 27.5% were intermediate risk (1), and 49.8% were high risk (>= 2). The CHA(2)DS(2)-VASc risk score reclassified 16,722 patients such that 7.8% were defined low risk, 13.8% intermediate risk and 78.4% high risk. Of the elderly cohort (>= 65 years) with definite NVAF visits (at least two encounters 30 days apart, n = 8780), 49% were taking warfarin within 90 days of diagnosis. Warfarin use did not differ across risk strata using either the CHADS(2) (p for trend = 0.85) or CHA(2)DS(2)-VASC (p = 0.35). In multivariable adjusted analyses, warfarin use was associated with substantially lower rates of death or cerebrovascular events for patients with CHADS(2) scores of 1 (OR 0.52, 95% CI 0.41 to 0.67) or >= 2 (OR 0.61, 95% CI 0.53 to 0.71), or CHA(2)DS(2)-VASc scores of >= 2 (OR 0.60, 95% CI 0.53 to 0.68). CONCLUSIONS: In elderly patients with NVAF and elevated CHADS(2) or CHA(2)DS(2)-VASC scores, warfarin users exhibited lower rates of cerebrovascular events and mortality. However, warfarin use did not differ across risk strata, another example of the risk--treatment paradox in cardiovascular disease. PMID- 22076013 TI - Systems of care for ST-elevation myocardial infarction in India. AB - The prevalence of coronary artery disease and ST-elevation myocardial infarction (STEMI) are increasing in India. Although recent publications have focused on improving preventive measures in developing countries, less attention has been placed on the acute management of STEMI. Recent policy changes in India have provided new opportunities to address existing barriers but require greater investment and support in the coming years. PMID- 22076014 TI - High platelet reactivity to multiple agonists during aspirin and clopidogrel treatment is indicative of a global hyperreactive platelet phenotype. PMID- 22076015 TI - The neglected role of blood pressure in acute heart failure syndrome. PMID- 22076017 TI - Final kissing balloon inflations after main vessel stenting in coronary bifurcations: not always, but sometimes. PMID- 22076016 TI - Very early diagnosis of chest pain by point-of-care testing: comparison of the diagnostic efficiency of a panel of cardiac biomarkers compared with troponin measurement alone in the RATPAC trial. AB - OBJECTIVE: To assess the impact of triple marker testing on patient management and the diagnostic efficiencies of different biomarker strategies examined. DESIGN: A prospective randomised trial of triple marker testing by point-of-care testing (POCT); the Randomised Assessment of Panel Assay of Cardiac markers (RATPAC) study. SETTING: Six emergency departments. PATIENTS: Low-risk patients presenting with chest pain to diagnostic assessment with a cardiac panel measured by POCT or to diagnosis when biomarker measurement was based on central laboratory testing. Interventions 1125 patients were randomly assigned to POCT measurement of the triple marker panel of cardiac troponin I (cTnI), myoglobin and the MB isoenzyme of creatine kinase (CK-MB) on admission and 90 min from admission. MAIN OUTCOME MEASURES: Myocardial infarction (MI) was defined by the universal definition of MI. The following diagnostic strategies were compared by receiver operator characteristic (ROC) curve analysis and comparison of area under the curve (AUC): individual marker values, change (Delta) in CK-MB and myoglobin and the combination of presentation or 90 min value plus Delta value. RESULTS: Admission sample measurement of cTnI was the most diagnostically efficient AUC 0.96 (0.93-0.98) with areas under the ROC curve statistically significantly greater than CK-MB 0.85 (0.80-0.90) and myoglobin 0.75 (0.68-0.81). At 90 min cTnI measurement had the highest AUC 0.95 (0.87-1.00) but was statistically significantly different only from Deltamyoglobin and DeltaCK-MB. CONCLUSION: Measurement of cTnI alone is sufficient for diagnosis. Measurement of a marker panel does not facilitate diagnosis. PMID- 22076019 TI - Effects of atorvastatin on endothelial function and the expression of proinflammatory cytokines and adhesion molecules in young subjects with successfully repaired coarctation of aorta. AB - OBJECTIVE: To investigate the effects of atorvastatin on endothelial function and low-grade systemic inflammation in subjects with successful surgery for aortic coarctation repair (SCR). DESIGN: Open-label study. SETTING: Outpatients visiting the adult congenital heart disease department of our hospital. PATIENTS: 34 young people with SCR. INTERVENTIONS: Patients with SCR received atorvastatin 10 mg/day (n=17) or no treatment (n=17) for 4 weeks. At baseline and at 4 weeks, endothelial function was assessed by flow-mediated dilatation (FMD) of the right brachial artery, and blood samples were obtained. Serum levels of interleukin (IL) 1b, IL-6 and soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined by ELISA. MAIN OUTCOME MEASURES: Effects of treatment on FMD and serum levels of IL-1b, IL-6 and sVCAM-1. RESULTS: FMD in the atorvastatin group was significantly improved after 4 weeks (from 6.46+/-0.95% to 11.24+/-1.38%, p<0.01), while remaining unchanged in the control group (from 6.74+/-0.58% to 6.95+/-0.53%, p=NS). Even though atorvastatin had no effect on serum IL-6 levels (0.62 (0.37-0.88) pg/ml to 0.53 (0.28-0.73) pg/ml, p=NS), it significantly reduced circulating levels of IL-1b (from 1.17 (0.92-1.77) pg/ml to 1.02 (0.75 1.55) pg/ml, p<0.05) and sVCAM-1 (from 883.4 (660.3-1093.1) ng/ml to 801.4 (566.7 1030.2) ng/ml, p<0.05). No changes were seen in serum levels of IL-6, IL-1b and sVCAM-1 in the control group after 4 weeks compared with baseline (p=NS for all). CONCLUSIONS: Atorvastatin treatment for 4 weeks in subjects with SCR significantly improved endothelial function and suppressed systemic inflammatory status by decreasing circulating levels of IL-1b and sVCAM-1. PMID- 22076020 TI - Mistaken conclusions. PMID- 22076021 TI - Cost-effectiveness of transcatheter aortic valve replacement in patients ineligible for conventional aortic valve replacement. AB - OBJECTIVE: To assess the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared with medical management in patients with severe aortic stenosis who are ineligible for conventional aortic valve replacement (SAVR) from the perspective of the UK National Health Service. DESIGN: Probabilistic decision analytical model. METHODS: A decision analytical model was developed to assess the costs and benefits associated with both interventions over a 10-year time horizon. A literature review was performed to identify relevant clinical evidence. Health-related quality of life and mortality were included using data from the PARTNER clinical trial (cohort B). Unit costs were taken from national databases. Costs and benefits were discounted at 3.5% per year, and extensive sensitivity analyses (probabilistic and deterministic) were performed to explore the impact of uncertainty on the cost-effectiveness estimates. MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratio (ICER) with benefits expressed as quality-adjusted life years (QALYs). RESULTS: The base case ICER was approximately L16,100 per QALY gained. At a cost-effectiveness threshold of L20,000 per QALY gained, the probability that TAVI was cost-effective compared with medical management was 1.00. The results were robust to changes in key clinical parameters as well as choice of baseline survival data. The observed PARTNER survival data only have to be extrapolated for 2 years to generate an ICER below L30 000 per QALY gained, which is the upper value of the threshold range used by the National Institute for Health and Clinical Excellence in the UK. CONCLUSIONS: TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis who are currently ineligible for SAVR. PMID- 22076022 TI - Prevalence and outcome of subclinical rheumatic heart disease in India: the RHEUMATIC (Rheumatic Heart Echo Utilisation and Monitoring Actuarial Trends in Indian Children) study. AB - OBJECTIVE: To study the prevalence and medium term outcome of subclinical rheumatic heart disease (RHD) in India. DESIGN: Cross sectional echocardiographic screening study. SETTING: School children aged 5-15 years living in rural areas of north India. PATIENTS: A cross sectional echocardiographic screening study was carried out among 6270 randomly selected school children aged 5-15 years (10.8 +/ 2.6 years; 52.7% male). Of all the abnormal cases, 100 children (78%) were restudied at a mean follow-up of 15.4 +/- 6.6 months. INTERVENTION: Echocardiographic screening. MAIN OUTCOME MEASURE: Echocardiography-Doppler criteria based prevalence of RHD. RESULTS: Clinical examination detected mitral regurgitation in five patients and the estimated prevalence of clinical RHD was 0.8/1000 school children. Echocardiography-Doppler diagnosed RHD in 128 cases, giving a prevalence of 20.4/1000 school children (95% CI 16.9 to 23.9/1000 children). On multivariate analysis, older age (OR 1.93, 95% CI 1.29 to 2.88; p = 0.001), female sex (OR 1.84, 95% CI 1.25 to 2.72; p = 0.002) and government funded school student, which is a surrogate measure of lower socioeconomic status (OR 1.55, 95% CI 1.02 to 2.34; p = 0.039) were found to be independent predictors of RHD. On follow up, the severity of subclinical RHD was non-progressive in 68 children (68%) while it worsened in four (4%) and regressed in 28 children (28%). CONCLUSIONS: The prevalence of RHD is several fold higher using echocardiographic screening compared with clinical examination. The prevalence is higher among girls and children of lower socioeconomic status. In the majority of cases, subclinical RHD appears to be non-progressive on medium term follow up. Routine echocardiographic screening may be indicated in populations at high risk of RHD. PMID- 22076023 TI - Reading Skills in Children with Multichannel Cochlear-lmplant Experience. AB - Forty children with prelingual, profound deafness who received the Nucleus multichannel cochlear implant between the ages of 2 and 13 years participated in this study. The children had an average of 63.3 months (SD=24 months) of experience with their cochlear implants. A majority of the children used simultaneous communication and attended public-school programs at the time of testing. Reading achievement was assessed using the Paragraph Comprehension subtest of the Woodcock Reading Mastery Test-Revised, Form G (1987). This study compared the reading-achievement levels of this group of cochlear-implant users with the results of previous studies of children with profound hearing losses who did not have the benefit of cochlear implants. Results indicated that nearly one half of the children in this study were reading at or within 8 months of their grade level. The reading-grade quotient of .74 was calculated based upon the slope of the regression line for the plot of years in school and reading grade level achieved. This finding indicates that using a cochlear implant has a positive effect on reading achievement level. PMID- 22076025 TI - Symbionts and pathogens: what is the difference? AB - The ecological relationships that organisms establish with others can be considered as broad and diverse as the forms of life that inhabit and interact in our planet. Those interactions can be considered as a continuum spectrum, ranging from beneficial to detrimental outcomes. However, this picture has revealed as more complex and dynamic than previously thought, involving not only factors that affect the two or more members that interact, but also external forces, with chance playing a crucial role in this interplay. Thus, defining a particular symbiont as mutualist or pathogen in an exclusive way, based on simple rules of classification is increasingly challenging if not unfeasible, since new methodologies are providing more evidences that depict exceptions, reversions and transitions within either side of this continuum, especially evident at early stages of symbiotic associations. This imposes a wider and more dynamic view of a complex landscape of interactions. PMID- 22076026 TI - A Statistical Approach to Thermal Management of Data Centers Under Steady State and System Perturbations. AB - Temperature control for a large data center is both important and expensive. On the one hand, many of the components produce a great deal of heat, and on the other hand, many of the components require temperatures below a fairly low threshold for reliable operation. A statistical framework is proposed within which the behavior of a large cooling system can be modeled and forecast under both steady state and perturbations. This framework is based upon an extension of multivariate Gaussian autoregressive hidden Markov models (HMMs). The estimated parameters of the fitted model provide useful summaries of the overall behavior of and relationships within the cooling system. Predictions under system perturbations are useful for assessing potential changes and improvements to be made to the system. Many data centers have far more cooling capacity than necessary under sensible circumstances, thus resulting in energy inefficiencies. Using this model, predictions for system behavior after a particular component of the cooling system is shut down or reduced in cooling power can be generated. Steady-state predictions are also useful for facility monitors. System traces outside control boundaries flag a change in behavior to examine. The proposed model is fit to data from a group of air conditioners within an enterprise data center from the IT industry. The fitted model is examined, and a particular unit is found to be underutilized. Predictions generated for the system under the removal of that unit appear very reasonable. Steady-state system behavior also is predicted well. PMID- 22076024 TI - Gold nanoparticles: preparation, properties, and applications in bionanotechnology. AB - Gold nanoparticles (AuNPs) are important components for biomedical applications. AuNPs have been widely employed for diagnostics, and have seen increasing use in the area of therapeutics. In this mini-review, we present fabrication strategies for AuNPs and highlight a selection of recent applications of these materials in bionanotechnology. PMID- 22076027 TI - Cross-effects of nickel contamination and parasitism on zebra mussel physiology. AB - Aquatic organisms are exposed to pollution which may make them more susceptible to infections and diseases. The present investigation evaluated effects of nickel contamination and parasitism (ciliates Ophryoglena spp. and intracellular bacteria Rickettsiales-like organisms), alone and in combination, on biological responses of the zebra mussel Dreissena polymorpha, and also the infestation abilities of parasites, under laboratory controlled conditions. Results showed that after 48 h, more organisms were infected in nickel-exposed groups, which could be related to weakening of their immune system. Acting separately, nickel contamination and infections were already stressful conditions; however, their combined action caused stronger biological responses in zebra mussels. Our data, therefore, confirm that the parasitism in D. polymorpha represents a potential confounding factor in ecotoxicological studies that involve this bivalve. PMID- 22076028 TI - Insecticides reduce survival and the expression of traits associated with carnivory of carnivorous plants. AB - While agrochemical pollution is thought to be an important conservation threat to carnivorous plants, the effects of insecticides on these taxa have not been quantified previously. Using a combination of lab- and field-based experiments, we tested the effects of commercial and technical grades of three widely used insecticides (carbaryl, lambda-cyhalothrin, and malathion) on survival and the expression of traits associated with carnivory of pink sundews (Drosera capillaris) and Venus flytraps (Dionaea muscipula). Commercial grades were generally more harmful than technical grades under lab and field conditions, but all three insecticides were capable of reducing both survival and the expression of traits associated with carnivory within recommended application rates. However, pink sundews appeared to be more susceptible to insecticides than Venus flytraps, perhaps because of larger numbers of digestive glands on the leaf surfaces. We make several recommendations for future research directions, such as examining the long-term effects of insecticides on carnivorous plant populations, for example in terms of growth rates and fitness. Additionally, future research should include representative species from a wider-range of carnivorous plant growth forms, and explore the mechanism by which insecticides are harming the plants. Given the effects we observed in the present study, we suggest that the use of insecticides should be carefully managed in areas containing vulnerable carnivorous plant species. PMID- 22076029 TI - Treatment of cancer cachexia in mice by combination of dsRNA-dependent protein kinase inhibitor and medroxyprogesterone acetate. AB - Inhibitor of dsRNA-dependent protein kinase (PKRI) and medroxyprogesterone acetate (MPA) improve cancer cachexia via different mechanisms. We aimed to compare these two drugs, alone or in combination, in cancer cachexia in mice. Forty male BABL/c mice aged 6-8 weeks were randomly divided into PKRI, MPA, PKRI+MPA, placebo, and healthy control groups. The first 4 groups were injected with colon-26 adenocarcinoma and fed for 12 days and then treated with PKRI and MPA alone or in combination for 7 days. Body weight, tumor volume, wet weight of gastrocnemius muscle, serum levels of nutritional markers and cytokines were measured. The tumor growth (volume and weight) of mice treated with PKRI, MPA alone or PKRI+MPA was slower than that of placebo group. Wet weight of gastrocnemius muscle was significantly higher in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). All tumor-bearing mice had a significantly lower level of blood glucose, higher level of serum triglyceride and lower level of serum albumin compared with healthy control (P<0.001). However, PKRI, MPA and PKRI+MPA groups had a significant higher level of blood glucose and lower level of serum triglyceride compared with placebo group (P<0.001). All tumor bearing mice had a significant higher level of serum TNF-alpha, IL-1 and IL-6 compared with healthy control (P<0.001). Serum level of TNF-alpha and IL-6 was significantly lower in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). PKRI alone and combination therapy with PKRI and MPA reduce tumor growth and may alleviate cachexia. PMID- 22076030 TI - TUNEL-positive cells in the surgical border of an amputation due to infected diabetic foot. AB - Diabetic infected foot is the outcome of progressive vascular and neurological damage caused by persistent chronic hyperglycemia. Due to acute hypoxia and infection, the tissues develop extensive necrosis and gangrene, which often require amputation. The decision regarding the level of amputation relies mainly on the personal experience of the surgeon who must identify the healthy tissue without necrosis. However, tissue cells under stress may succumb before clear evidence of necrosis is present. In this study, dying cells with DNA damage were identified in the necrotic lesions and surgical borders of amputations. Therefore, the main purpose of this study was to identify apoptosis in the surgical borders of amputations required to treat infected diabetic foot. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated bio dUTP nick-end labeling (TUNEL) in the superficial and deep tissues of wounds, and in the surgical borders of 10 consecutive adult patients with diabetes mellitus type 2 (DM2) who underwent amputation due to infected diabetic foot. The severity of the disease was classified by the Acute Physiological and Chronic Health Evaluation II (APACHE II) score on admission, and laboratory data were collected and bacteriological cultures were obtained from the lesions. The ankle/arm blood pressure index was measured, the blood flow in the affected limb was evaluated by high-resolution ultrasonography and color Doppler and pulse oximetry were performed during surgery. A total of 5 males and 5 females, aged 45-84 years (58.8 +/- 14.1), were included. The APACHE II score was 2-18 points (8 +/- 5.7). A total of 9 patients developed sepsis and 2 succumbed. A total of 5 patients required above-ankle amputation, and 5 required toe disarticulation. The ankle/arm blood pressure index ranged from 0.23-0.85 (0.51 +/- 0.23). Apoptotic cells were found in ulcers and abscesses, and in areas without necrosis. In the surgical borders of the amputations, apoptotic cells were found in skeletal muscle, blood vessels and peripheral nerves, particularly Schwann cells. Morphometric analysis revealed that the extent of apoptosis was 2-3 logarithms higher in the surgical borders of the infected diabetic foot compared to the venous ulcers, which were used as the reference. In conclusion, apoptosis was identified in regenerating tissues within diabetic foot wounds and in the surgical borders of amputations, where the surgeon considered the tissues to be undamaged. This information suggests that apoptosis may be present before visible signs of necrosis appear in the diabetic foot and may be caused by hypoxia, acidosis or proinflammatory cytokines. The extent of apoptosis in tissues proximal to necrotic areas may anticipate the development of diabetic foot and help the surgeon to make decisions regarding the need and extent of amputation. PMID- 22076031 TI - Glucocorticoid sensitivity in mood disorders. AB - In this review, we provide an overview of recent literature on glucocorticoid (GC) sensitivity in mood disorders. Assessing GC sensitivity is often performed by measuring the cortisol awakening rise (CAR), by challenging the hypothalamic pituitary-adrenal (HPA) axis using a dexamethasone suppression test (DST) or a dexamethasone/cortisol-releasing hormone test (DEX/CRH); more recently by measuring cortisol as a retrospective calendar in scalp hair. The main findings in mood disorders are higher mean cortisol levels in hair samples and a higher CAR, showing a hyperactivity of the HPA axis. This is in line with the mild resistance for GCs previously observed in challenge tests during mood episodes. GC sensitivity is partly determined by polymorphisms in the genes encoding receptors and other proteins involved in the regulation of the HPA axis. We shortly discuss the glucocorticoid receptor, as well as the mineralocorticoid receptor, the cortisol-releasing hormone receptor-1, and the glucocorticoid receptor co-chaperone FKBP5. Data clearly indicate genetic changes, along with epigenetic changes which influence the set-point and regulation of the HPA axis. Early trauma, as well as influences in utero, appears to be important. Future research is necessary to further clarify the biological background and consequences of an individual's cortisol exposure in relation to mood. PMID- 22076032 TI - Accessory mental nerve: case report, review and its role in trigeminal neuralgia. AB - The presence of accessory mental nerve (AMN) is rare and only few cases have been reported. Peripheral neurectomy of the mental nerve is one of the treatments of choice in cases of trigeminal neuralgia (TGN) affecting the mental nerve. Failure to remove the mental nerve with all its branches completely is the main reason behind its regrowth leading to recurrence of the disease. Presence of AMN may be missed out during routine surgery leading to persistence of the neuralgic pain associated with the AMN. The purpose of this article is to present a case where an AMN was found accidently after excision of the mental nerve in a case of TGN. The AMN was dissected to its complete length and excised. The patient was followed up on monthly basis and there was no recurrence found 24 months postoperatively. PMID- 22076033 TI - Complexation of novel diglycolamide functionalized calix[4]arenes: unusual extraction behaviour, transport, and fluorescence studies. AB - Three diglycolamide functionalized calix[4]arenes (calix[4]-nDGA) were synthesized and evaluated for their extraction behaviour towards lanthanide/actinide ions. Exceptionally high D(Am) and D(Pu) values indicate these radiotoxic elements can be selectively removed from nuclear waste solutions. Transport and laser induced fluorescence studies indicated strong complexation of the trivalent metal ions with the calix[4]-4DGA ligand. PMID- 22076034 TI - Maspin increases Ku70 acetylation and Bax-mediated cell death in cancer cells. AB - Ku70, a DNA repair protein, was recently identified as a critical anti-apoptotic protein that inhibits Bax translocation to mitochondria. The dissociation of Bax from Ku70 is essential for the apoptotic activity of Bax. Here, we show that maspin, a tumor suppressor protein frequently lost in cancer, regulates this process. Maspin increased cell death in a Ku70 acetylation-dependent manner. Maspin inhibited histone deacetylase 1 (HDAC1) and thus increased the acetylation of Ku70 and the dissociation of Bax from Ku70, which led to the induction of apoptosis. These results reveal maspin as a Ku70-interacting molecule and provide the basis for a new endogenous acetylation-based control mechanism that reduces Ku70-mediated sequestration of Bax from mitochondria. PMID- 22076035 TI - Cobedding of twins or higher-order multiples: NANN position statement #3053. PMID- 22076036 TI - Group medical claims as a source of information on worker health and potentially work-related diseases. AB - OBJECTIVE: To help address underrecognition of occupational illnesses and support planning of workplace health initiatives. METHODS: Data from Highmark Inc., a health care insurer headquartered in Pittsburgh and Camp Hill, Pennsylvania, was used to calculate age and gender-adjusted rates of 15 diseases by industry and broad industry sector. RESULTS: Significant industry differences in disease rates were observed, some corresponding to known differences in workplace risk factors. CONCLUSION: Group medical claims offer timely, relatively low cost, longitudinal data on rates of physician-diagnosed cases and costs of many diseases for large populations. Limitations of medical claims data include inaccuracies in industry coding, lack of occupation codes, and lack of key variables that affect health. Yet, some elevated industry rates suggest potential new targets for wellness programs and evaluation of possible workplace health risks. PMID- 22076037 TI - Messenger RNA expression and genetic polymorphisms of cell cycle control genes and chromosomal aberrations in Chinese vinyl chloride monomer-exposed workers. AB - OBJECTIVE: To evaluate the expressions of p53, p21, and CCND1 in the peripheral blood lymphocytes of vinyl chloride monomer (VCM)-exposed workers and potential relationships with their exposures, polymorphisms, and chromosomal aberrations. METHODS: The study was performed on 77 occupationally VCM-exposed workers and 43 unexposed controls. The quantities of mRNA expression of p53, p21, and CCND1 genes were detected by real-time polymerase chain reaction. RESULTS: p53 mRNA expression of VCM-low- and high-exposure groups was significantly lower than that of nonexposed group (P < 0.001), but p21 mRNA expression of the two VCM-exposed groups was significantly higher than that of the nonexposed group (P < 0.001). This study did not find the relationship between chromosomal aberrations, genotypes, and the expression of p53, p21, and CCND1. CONCLUSIONS: Messenger RNA expressions of p53 and p21 are changed with VCM-exposure status. PMID- 22076038 TI - Preterm, low-birth-weight deliveries, and farmwork among Latinas in California. AB - OBJECTIVE: To examine the association between preterm and low-birth-weight (PTLBW) delivery and maternal occupation among Latina women in California. METHODS: A cohort of 1024 Latina women in Stockton, California, was observed from baseline to delivery. The association between PTLBW delivery and maternal occupation (farmwork, nonfarmwork, no work) was analyzed using multiple logistic regression models. RESULTS: Demographic characteristics varied widely between the three occupation groups. The adjusted odds ratio of a PTLBW delivery for farmworkers compared with women who did not work was 1.28 (95% CI, 0.65 to 2.54). CONCLUSIONS: We did not observe a statistically significant association between PTLBW delivery and farmwork in this population. Nevertheless, the relationship between acculturation and risky health behaviors suggests that studies investigating the association between maternal employment and adverse pregnancy outcomes among Latinas need to account for a participant's acculturation status. PMID- 22076039 TI - Are occupational factors and mental difficulty associated with occupational injury? AB - OBJECTIVE: To evaluate the associations between biomechanical, physical, and psychological demands and occupational injury according to depressive symptoms severity. METHODS: Two thousand eight hundred eighty-two French working people completed a questionnaire covering sociodemographic characteristics, smoking, alcohol consumption, obesity, job, chronic diseases, depressive symptoms, and injuries during the previous 2-year period. Data were analyzed using logistic regression. RESULTS: Occupational injury (9.2%) strongly related to biomechanical, physical, and psychological demands among depressive-symptoms-free workers (odds ratios ranging from 1.35 to 3.15). These relationships were stronger among the workers with depressive symptoms without medical treatment (11.9%) and among those with persistent symptoms despite a treatment (1.7%), with odds ratios up to 12. These associations were partially confounded (up to 51%) by unhealthy behaviors, health status, and chronic diseases. CONCLUSIONS: High occupational demands and depressive symptoms can be early identified and monitored to prevent injury. PMID- 22076040 TI - Evaluation of occupational exposure to magnetic fields and motor neuron disease mortality in a population-based cohort. AB - OBJECTIVE: Epidemiologic evidence for the association between electromagnetic fields and amyotrophic lateral sclerosis, the most common form of motor neuron disease (MND), has been inconclusive. We evaluated the association between electromagnetic fields and MND among workers in occupations potentially exposed to magnetic fields METHODS: MND mortality (ICD-9 335.2) was examined in the National Longitudinal Mortality Study using multivariable proportional hazards models. Occupational exposure to magnetic fields was determined on the basis of a population-based job-exposure matrix. Age at entry, education, race, sex, and income were considered for inclusion as covariates RESULTS: After adjusting for age, sex, and education, there were no increased risks of MND mortality in relation to potential magnetic field exposure, with hazard ratios around the null in all magnetic field exposure quartiles CONCLUSIONS: Our study does not provide evidence for an association between magnetic field exposure and MND mortality. PMID- 22076041 TI - The impact of workplace risk factors on long-term musculoskeletal sickness absence: a registry-based 5-year follow-up from the Oslo health study. AB - OBJECTIVE: To determine the influence of work-related risk factors by gender on long-term sickness absence with musculoskeletal diagnoses (LSM). METHODS: Data from the Oslo Health Study were linked to the historical event database of Statistics Norway. Eight thousand three hundred thirty-three participants were followed from 2001 through 2005. Generalized linear models were used to compute risk differences for LSM. RESULTS: In total, 12.6% of the women and 8.8% of the men experienced at least one LSM. Statistically, significant LSM risk increases between 0.039 and 0.086 in association with work environment were found for heavy physical work, low job control (men only), low support from superior (women only), and having shift/night work (men only). CONCLUSIONS: Women exhibited a higher LSM risk, but the associations with job exposures were stronger for men. This should be addressed when occupational health services give advice on preventive measures. PMID- 22076042 TI - Efficient antitumor effects of carrier cells loaded with a fiber-substituted conditionally replicating adenovirus on CAR-negative tumor cells. AB - Carrier cells delivering a conditionally replicating adenovirus (CRAd), which selectively replicates in tumor cells and induces tumor cell lysis, have promising potential for treatment of cancer because CRAd-loaded carrier cells evade inhibition by neutralizing anti-adenovirus (Ad) antibodies and because the carrier cells are locally retained at the injection point after local injection. A previous study by Hamada et al. demonstrated that carrier cells (CRAd containing cell fragments derived from the carrier cells) are engulfed into the target cells, probably through a pathway independent of the primary receptor for Ad, the coxsackievirus and Ad receptor (CAR) (Mol Ther, 15: 1121-1128; 2007); however, it remains to be elucidated whether carrier cells infected with a conventional CRAd, which is composed of subgroup-C Ad serotype-5 (Ad5), mediate antitumor effects on CAR-negative cells. In order to examine whether carrier cells delivering a conventional CRAd (Carrier-F5) induce lysis of CAR-negative tumor cells, CAR-positive and CAR-negative tumor cells were incubated with Carrier-F5. Carrier-F5 mediated efficient killing of CAR-positive tumor cells; however, CAR-negative tumor cells were almost refractory to Carrier-F5. On the other hand, carrier cells loaded with a fiber-substituted CRAd containing fiber proteins of Ad serotype-35 (Ad35) (CRAd-F35), which binds to human CD46 for infection, showed efficient killing of both CAR-positive and CAR-negative tumor cells. Intra-tumoral injection of carrier cells loaded with CRAd-F35 (Carrier F35) also resulted in efficient regression of both CAR-positive and CAR-negative tumors. These results demonstrated that the expression levels of receptors for Ad are an important factor for CRAd-loaded carrier cell-mediated cancer therapy, and that Carrier-F35 would have potential as a cancer treatment for not only CAR positive tumors but also CAR-negative tumors. PMID- 22076043 TI - Chemovirotherapy for head and neck squamous cell carcinoma with EGFR-targeted and CD/UPRT-armed oncolytic measles virus. AB - First-line treatment of recurrent and/or refractory head and neck squamous cell carcinoma (HNSCC) is based on platinum, 5-fluorouracil (5-FU) and the monoclonal antiEGFR antibody cetuximab. However, in most cases this chemoimmunotherapy does not cure the disease, and more than 50% of HNSCC patients are dying because of local recurrence of the tumors. In the majority of cases, HNSCC overexpress the epidermal growth factor receptor (EGFR), and its presence is associated with a poor outcome. In this study, we engineered an EGFR-targeted oncolytic measles virus (MV), armed with the bifunctional enzyme cytosine deaminase/uracil phosphoribosyltransferase (CD/UPRT). CD/UPRT converts 5-fluorocytosine (5-FC) into the chemotherapeutic 5-FU, a mainstay of HNSCC chemotherapy. This virus efficiently replicates in and lyses primary HNSCC cells in vitro. Arming with CD/UPRT mediates efficient prodrug activation with high bystander killing of non infected tumor cells. In mice bearing primary HNSCC xenografts, intratumoral administration of MV-antiEGFR resulted in statistically significant tumor growth delay and prolongation of survival. Importantly, combination with 5-FC is superior to virus-only treatment leading to significant tumor growth inhibition. Thus, chemovirotherapy with EGFR-targeted and CD/UPRT-armed MV is highly efficacious in preclinical settings with direct translational implications for a planned Phase I clinical trial of MV for locoregional treatment of HNSCC. PMID- 22076045 TI - Low prevalence of Haemoproteus infections in Chiffchaffs. AB - Parasite prevalence is an important variable in many evolutionary and ecological studies. In birds, haemosporidian blood parasites have been in focus of many comparative analyses. Because low prevalence is difficult to estimate precisely and that studies finding low prevalence are more likely to remain unpublished, our knowledge of parasite prevalence is biased towards highly infected taxa. Species with naturally low levels of infection are nonetheless interesting as they may provide models for studying the evolution of pathogen resistance. In the present study we show that the prevalence of Haemoproteus parasites is markedly lower in several taxa within the widely distributed chiffchaff species-complex compared to other species within the genus Phylloscopus. Since chiffchaffs, P. collybita, commonly coexists in the same habitat as congeners frequently infected with Haemoproteus parasites, immediate ecological variables like abundance of vectors can hardly explain this difference. Some of the parasites infecting coexisting congeners are broad host generalists leaving it enigmatic why chiffchaffs are almost free of Haemoproteus infections. We propose that detailed infection experiments are needed to illuminate whether chiffchaffs possess a genetic immunity against Haemoproteus parasites or if other more subtle ecological processes, like anti-vector behaviour, play a role in its generally low level of infestation. PMID- 22076044 TI - Oncolytic herpes simplex virus expressing yeast cytosine deaminase: relationship between viral replication, transgene expression, prodrug bioactivation. AB - Yeast cytosine deaminase (yCD) is a well-characterized prodrug/enzyme system that converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), and has been combined with oncolytic viruses. However, in vivo studies of the interactions between 5-FC bioactivation and viral replication have not been previously reported, nor have the kinetics of transgene expression and the pharmacokinetics of 5-FC and 5-FU. We constructed a replication-conditional Herpes simplex virus 1 (HSV-1) expressing yCD and examined cytotoxicity when 5-FC was initiated at different times after viral infection, and observed that earlier 5-FC administration led to greater cytotoxicity than later 5-FC administration in vitro and in vivo. In animal models, 12 days of 5-FC administration was superior to 6 days, but dosing beyond 12 days did not further enhance efficacy. Consistent with the dosing schedule results, both viral genomic DNA copy number and viral titers were observed to peak on Day 3 after viral injection and gradually decrease thereafter. The virus is replication-conditional and was detected in tumors for as long as 2 weeks after viral injection. The maximum relative extent of yCD conversion of 5-FC to 5-FU in tumors was observed on Day 6 after viral injection and it decreased progressively thereafter. The observation that 5-FU generation within tumors did not lead to appreciable levels of systemic 5-FU (<10 ng ml-1) is important and has not been previously reported. The approaches used in these studies of the relationship between the viral replication kinetics, transgene expression, prodrug administration and anti-tumor efficacy are useful in the design of clinical trials of armed, oncolytic viruses. PMID- 22076046 TI - Active hexose correlated compound inhibits the expression of proinflammatory biomarker iNOS in hepatocytes. AB - BACKGROUND/AIMS: Excess production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as proinflammatory biomarker in liver injury. The application of active hexose correlated compound (AHCC) as a functional food in complementary and alternative medicine has increased. The possibility that AHCC might inhibit iNOS induction was investigated as a potential liver protective effect. METHODS: Hepatocytes were isolated from rats by collagenase perfusion and cultured. Primary cultured hepatocytes were treated with interleukin-1beta in the presence or absence of AHCC-sugar fraction (AHCC-SF). RESULTS AND CONCLUSION: AHCC-SF inhibited the production of NO and reduced expressions of iNOS mRNA and its protein. AHCC-SF had no effects on either IkappaB degradation or nuclear factor-kappaB (NF-kappaB) activation. In contrast, AHCC-SF inhibited the upregulation of type I interleukin-1 receptor (IL-1RI) through the inhibition of Akt phosphorylation. Transfection experiments with iNOS promoter-luciferase constructs revealed that AHCC-SF reduced the levels of iNOS mRNA at both promoter transactivation and mRNA stabilization steps. AHCC-SF inhibited the expression of iNOS gene antisense transcript, which is involved in iNOS mRNA stabilization. These findings demonstrate that AHCC-SF suppresses iNOS gene expression through a IkappaB/NF-kappaB-independent but Akt/IL-1RI-dependent pathway, resulting in the reduction of NO production. AHCC-SF may have therapeutic potential for various liver injuries. PMID- 22076047 TI - Variational study of the quantum phase transition in the bilayer Heisenberg model with bosonic RVB wavefunction. AB - We study the ground state phase diagram of the bilayer Heisenberg model on a square lattice with a bosonic resonating valence bond (RVB) wavefunction. The wavefunction has the form of a Gutzwiller projected Schwinger boson mean-field ground state and involves two variational parameters. We find the wavefunction provides an accurate description of the system on both sides of the quantum phase transition. In particular, through the analysis of the spin structure factor, ground state fidelity susceptibility and the Binder moment ratio Q(2), a continuous transition from the antiferromagnetic ordered state to the quantum disordered state is found at the critical coupling of alpha(c) = J(?)/J(?) ~ 2.62, in good agreement with the result of quantum Monte Carlo simulation. The critical exponent estimated from the finite size scaling analysis (1/nu ~ 1.4) is consistent with that of the classical 3D Heisenberg universality class. PMID- 22076048 TI - The use of religion and spirituality in psychotherapy: enablers and barriers. AB - The use of religion and spirituality in psychotherapy has been a contentious issue for decades. This paper explores and describes whether psychologists would use religion and spirituality in psychotherapy as well as enablers and barriers in this regard. A qualitative exploratory descriptive method was followed using purposive sampling to obtain a sample of clinical and counselling psychologists. The focus group strategy was used to collect the data, and Tesch's model of content analysis was used to analyse the qualitative findings. Most participants expressed a willingness to discuss religion and spirituality with their clients. Participants also highlighted specific enablers and barriers to incorporating religion and spirituality in psychotherapy. This article has the potential to influence professional training in psychology and psychotherapy. PMID- 22076049 TI - HPV vaccine decision-making and acceptance: does religion play a role? AB - We conducted a web-based survey among 476 white, Black, and Hispanic parents or caregivers with daughter(s) between the ages of 9-17 to better understand how religion influences HPV vaccine acceptance. Catholic parents were more likely than nonaffiliated parents to have already vaccinated their daughters (vs. being undecided) (OR = 3.26, 95% CI = 1.06, 10.06). Parents with frequent attendance at religious services were more likely than parents who do not attend services to have decided against vaccination (vs. being undecided) (OR = 2.92, 95% CI = 1.25, 6.84). Directions for research and implications for interventions are addressed. PMID- 22076051 TI - Molecular cloning and characterization of a HSP70 gene from Schistosoma japonicum. AB - Schistosoma japonicum is the pathogen responsible for schistosomiasis japonica, one of the major infectious diseases targeted for prevention nationally in China. Expression of heat shock proteins (HSPs) following stress plays a very important biological role in many organisms including S. japonicum. Among the HSP family, the 70-kDa HSPs are most responsible for intracellular chaperone and extracellular immunoregulatory functions. Based on the published sequences in GenBank/EMBL (AF044412.1), open reading frame belonging to HSP70 protein corresponds to a full-length cDNA containing an open reading frame of 1,947 bp encoded of 648 amino acids was identified as HSP70 from schistosome. In this study, the coding region that we named rSj648/hsp70 was amplified from S. japonicum adult worm cDNA library, and the recombinant protein was expressed in vector pET32a(+) and purified using a Ni-NTA purification system. The target protein rSj648/hsp70 was determined by matrix-assisted laser desorption/ionization mass spectrometer after thrombin digestion and dialysis. Reverse transcriptase polymerase chain reaction and Western blotting analysis confirmed that Sj648/hsp70 could be expressed in the eggs, normal cercariae, ultraviolet-attenuated cercariae (UVAC), and adult worms of S. japonicum. Real time quantitative PCR analysis indicated that Sj648/hsp70 was expressed significantly higher in eggs than that in cercariae and adult worms, and the expression in UVAC was higher than that in normal cercariae. A thermotolerance assay showed that rSj648/hsp70 could protect Escherichia coli cells from heat damage. The detection of specific antibody levels by indirect enzyme-linked immunosorbent assay demonstrated that mice immunized with rSj648/hsp70 induced higher level of specific anti-rSj648/hsp70 IgG1 compared with those vaccinated with adjuvant alone, indicating that rSj648/hsp70 was able to elicit Th2-type bias immune response. Our results suggest that Sj648/hsp70 might be an important molecule in parasite-host interaction and display potential roles in mice immunoregulation system. PMID- 22076050 TI - Predominance of Blastocystis sp. subtype 4 in rural communities, Nepal. AB - Blastocystis sp. is a common intestinal parasite. To date, there have been sporadic and scanty studies on Blastocystis sp. carried out in rural communities in Nepal. We surveyed the prevalence of Blastocystis sp. and its possible associated risk factors, and reported the predominant Blastocystis sp. subtype in two rural communities, Bolde Phediche and Bahunipati, in Nepal. Human faecal samples were collected from 241 participants, cultured using in vitro cultivation and examined for Blastocystis sp. The presence of Blastocystis sp. in faecal samples was further confirmed by polymerase chain reaction (PCR) and subsequently genotyped using subtype-specific sequence tagged site (STS) primers. There were 26.1% (63/241) of the participants that were infected by Blastocystis sp. We detected 84.1% (53/63) of Blastocystis sp. subtype 4 infections in these rural communities. The unusually high prevalence of Blastocystis sp. subtype 4 can be attributed to the rearing of family-owned animals in barns built close to their houses. Eighty one percent (51/63) of the Blastocystis sp. infected participants drank not boiled or unfiltered water. The present study revealed that Blastocystis sp. could pose a health concern to the communities and travellers to the hilly area in Nepal. Infection may be transmitted through human-to-human, zoonotic and waterborne transmissions. We provide recommendations to ensure good public health practices. PMID- 22076052 TI - Ultrastructural changes during asexual multiple reproduction in Trichomonas vaginalis. AB - Trichomonas vaginalis, a flagellated protozoan parasite, is commonly found in the genitourinary tract of humans. Its mode of reproduction has always been reported to be binary fission. The high parasite numbers seen in a relatively short period in in vitro cultures led us to believe that there must be other modes of reproduction. The present study for the first time provides transformational evidence at the ultrastructural level seen in tropohozoites of T. vaginalis undergoing a multiple asexual mode of reproduction. The findings show that the single cell with a nucleus is capable of dividing to as many as eight nuclei within the cytoplasmic body. Before the commencement of division, the nucleus remained round or ovoid in shape with condensed chromatin masses and only a few endoplasmic reticula surrounding the nucleus. During the division, the nucleus started to elongate and become irregular in shape with visible chromatin masses condensing with the accumulation of numerous endoplasmic reticula. Nuclear division gave rise to as many as eight nuclei within a cell, which could be seen to be connected by numerous endoplasmic reticula. In addition, a high number of hydrogenosomes and vacuoles can be seen in multinucleated T. vaginalis compared with single nucleated T. vaginalis. This study confirms that multiple modes of nuclear division do exist in T. vaginalis and are a precursor to progeny formation. PMID- 22076054 TI - Prosthetic inlay resurfacing for the treatment of focal, full thickness cartilage defects of the femoral condyle: a bridge between biologics and conventional arthroplasty. AB - PURPOSE: Localized full thickness defects of the femoral condyle can be highly symptomatic. Treatment options for these lesions are numerous in young patients, however they become increasingly challenging in middle aged and older patients. In order to delay traditional joint replacement procedures and to provide a soft tissue and bone sparing alternative, this study assess a focal inlay resurfacing procedure. METHODS: Between 2004 and 2008, a consecutive series of 27 patients were treated with the Arthrosurface HemiCAP((r)) Focal Femoral Condyle Resurfacing Prosthesis and were assessed to study the clinical benefit of this procedure. Outcome measures included the KOOS, IKDC, HSS and WOMAC as well as physical and radiographic evaluation. RESULTS: Nineteen patients met the inclusion/exclusion criteria, 18 were available for review at a median follow-up of 34 months (range 20-57).The median age was 49 years (range 43-78). 63% had early arthritis, 5.2% localized osteonecrosis, and 31.6% had a focal traumatic full thickness defect. The follow-up total WOMAC score averaged 90.1 +/- 9.3, The KOOS showed very good to excellent scores in all domains and also when compared to age-matched normative data. Significant improvement was seen with the HSS Score. On IKDC examination, 83.4% had normal or nearly normal results. CONCLUSION: Focal femoral condyle resurfacing demonstrated excellent results for pain and function in middle-aged, well selected patients with full thickness cartilage and osteochondral defects. Patient profiling and assessment of confounding factors, in particular mechanical joint alignment; meniscal function; and healthy opposing cartilage surfaces, are important for an individual treatment approach and successful outcomes. LEVEL OF EVIDENCE: IV. PMID- 22076053 TI - The impact of a high tibial valgus osteotomy and unicondylar medial arthroplasty on the treatment for knee osteoarthritis: a meta-analysis. AB - PURPOSE: Both high tibial valgus osteotomy (HTO) and unicompartmental medial knee arthroplasty (UKA) are established methods for the treatment for moderate stages of OA. This is the first global meta-analysis to compare the long-term effects of both methods regarding survival, outcomes and complications of total arthroplasty. METHODS: Literature research was performed using established medical databases: MEDLINE (via PubMed), EMBASE (via OVID) and the Cochrane register. Criteria for inclusion were as follows: English or German papers, a clinical trial with a clear description of survival, an outcome evaluation using a well-described knee score and a follow-up >5 years. Statistical analysis was performed using the special meta-analysis software called "Comprehensive Meta Analysis" (version 2.0; Biostat, Englewood, NJ, USA). RESULTS: Final meta analysis after the full-text review included 46 studies about valgus HTO and 43 studies about medial UKA. There were no significant differences between valgus HTO and medial UKA in terms of the number of total required replacements. After a 5- to 8-year follow-up, 91.0% of the valgus HTO patients and 91.5% of medial UKA patients did not need a total replacement. This value was 84.4% for valgus HTOs and 86.9% for medial UKAs after a 9- to 12-year follow-up. Mean survival time to TKA was 9.7 years after valgus HTO and 9.2 years after medial UKA. Clinical outcome was significantly better after medial UKA in a 5- to 12-year follow-up. After more than 12 years, results were comparable in both groups. No significant differences were seen in the complication rates. CONCLUSIONS: This meta-analysis aimed to find the advantages and disadvantages of two established methods for the treatment for medial compartment knee osteoarthritis. Valgus HTO is more appropriate for younger patients who accept a slight decrease in their physical activity. Medial UKA is appropriate for older patients obtaining sufficient pain relief but with reduced physical activity. LEVEL OF EVIDENCE: II. PMID- 22076055 TI - Biomechanical evaluation of tenodesis reconstruction in ankle with deltoid ligament deficiency: a finite element analysis. AB - PURPOSE: Isolated deltoid ligament injuries are relatively uncommon but can be a significant source of pain and disability. Several approaches to deltoid reconstruction have been reported. However, there is no previous comparative study of Wiltberger, Deland, Kitaoka and Hintermann procedures with respect to biomechanical characteristics such as kinematics, ligaments and grafts stresses using finite element analysis. The purpose of this study was to evaluate the biomechanical results of those deltoid ligament reconstructions using finite element analysis. METHODS: A three-dimensional finite element model of the ankle including six bony structures, cartilage and nine principal ligaments surrounding the ankle joint complex was developed and validated. In addition to the intact model, superficial deltoid-deficient, deltoid-deficient, Wiltberger reconstruction, Deland reconstruction, Kitaoka reconstruction and Hintermann reconstruction models were simulated. Then, the forces in the ligaments and grafts and the kinematics of talus and calcaneus were predicted for an eversional or external torque through the range of ankle flexion. RESULTS: No reconstructions could completely restore the values for ankle flexibility and the stresses of the lateral ligaments to normality. The Kitaoka procedure was the most effective technique in eliminating external rotation displacement. The Deland procedure restored better the talar tilt than the other three reconstructions. CONCLUSION: This study showed that Kitaoka and Deland procedures have advantages with regard to rotational stabilities as well as ligaments stress in comparison with other methods. PMID- 22076057 TI - Aspergillus fumigatus densities in relation to forest succession and edge effects: implications for wildlife health in modified environments. AB - The hihi (or stitchbird, Notiomystis cincta) is a New Zealand endemic nectivorous forest bird now restricted to one pristine island. Relocation to establish viable hihi populations on other islands has been the main conservation action since the early 1980s. To date, hihi reintroductions to young growth islands have had poor success despite the absence of mammalian predators. It was thought that past failures were due to food limitation, but research suggests that food limitation alone cannot account for their poor survivorship. Post-mortems of dead hihi has shown that aspergillosis caused by Aspergillus fumigatus is a major mortality factor and there is current concern regarding their susceptibility to this fungal disease. In this paper we develop and assess the hypothesis that A. fumigatus limits hihi population viability on modified islands, and suggest that A. fumigatus is a potential indicator species for habitat disturbance. We report that the prevalence of A. fumigatus spores in the soil is much higher in young growth forests and forest edge habitats. Results suggest that hihi mortality rates between islands are potentially due to differential exposure to A. fumigatus spores. We assess relationships between habitat disturbance, A. fumigatus contamination and hihi mortality rates by testing the following predictions: (1) that densities of A. fumigatus spores will be higher on modified islands, (2) that densities of A. fumigatus spores on islands will be correlated with hihi mortality rates and (3) that densities of A. fumigatus spores will be higher at the forest edge than in the interior. We test each of these predictions using soil samples, air samples and samples of nectar from plant species fed on by hihi. PMID- 22076058 TI - STROBE-ME too! PMID- 22076060 TI - Acidic-functionalized ionic liquid as an efficient, green and reusable catalyst for hetero-Michael addition of nitrogen, sulfur and oxygen nucleophiles to alpha,beta-unsaturated ketones. AB - A series of acidic-functionalized ionic liquids were synthesized and applied to the hetero-Michael addition of nitrogen, sulfur and oxygen nucleophiles to alpha,beta-unsaturated ketones under solvent-free conditions. Notably, 1 methylimidazolium p-toluenesulfonic ([Hmim]OTs) was found to be the most efficient catalyst and could realize "homogeneous catalysis, two-phase separation". Additionally, the catalytic system has wide substrate scope and good to excellent yields (up to 99%) could be obtained at room temperature. PMID- 22076059 TI - Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis. AB - In previous studies evaluating whether different alcoholic beverages would protect against cardiovascular disease, a J-shaped relationship for increasing wine consumption and vascular risk was found; however a similar association for beer or spirits could not be established. An updated meta-analysis on the relationship between wine, beer or spirit consumption and vascular events was performed. Articles were retrieved through March 2011 by PubMed and EMBASE search and a weighed least-squares regression analysis pooled data derived from studies that gave quantitative estimation of the vascular risk associated with the alcoholic beverages. From 16 studies, evidence confirms a J-shaped relationship between wine intake and vascular risk. A significant maximal protection-average 31% (95% confidence interval (CI): 19-42%) was observed at 21 g/day of alcohol. Similarly, from 13 studies a J-shaped relationship was apparent for beer (maximal protection: 42% (95% CI: 19-58%) at 43 g/day of alcohol). From 12 studies reporting separate data on wine or beer consumption, two closely overlapping dose response curves were obtained (maximal protection of 33% at 25 g/day of alcohol). This meta-analysis confirms the J-shaped association between wine consumption and vascular risk and provides, for the first time, evidence for a similar relationship between beer and vascular risk. In the meta-analysis of 10 studies on spirit consumption and vascular risk, no J-shaped relationship could be found. PMID- 22076061 TI - Exploration of the binding of curcumin analogues to human P450 2C9 based on docking and molecular dynamics simulation. AB - Molecular docking and molecular dynamics (MD) simulations are used to investigate the interactions of curcumin analogues (CAs) with human cytochrome P450 2 C9 (CYP2C9 or 2 C9) and the conformations of their binding sites. In order to examine conformations of CAs/2 C9 and interaction characteristics of their binding sites, RMSDs, RMSFs, and B-factors are computed, and electrostatic and hydrophobic interactions between CAs and 2 C9 are analyzed and discussed. Results demonstrate that the most CAs studied lie 4~15 A above the heme of CYP2C9. The presence of CAs makes some residues in bound CYP2C9s become more flexible. In the binding sites of A0/2 C9 and C0/2 C9, the formation of H-bond networks (or CA water-residue bridges) enhances the interactions between CAs and 2 C9. The stronger inhibitory effects of A0, B0, and C0 on 2 C9 can be ascribed to stronger electrostatic and hydrophobic interactions in the binding sites of CAs/2 C9. PMID- 22076062 TI - Molecular dynamics simulation studies of betulinic acid with human serum albumin. AB - Betulinic acid (BA) is a naturally occurring pentacyclictriterpenoid possessing anti-retroviral, anti-cancer, and anti-inflammatory properties. Here, we studied the interaction of BA with human serum albumin (HSA) by using molecular docking, and molecular dynamic simulation methods. Molecular docking studies revealed that BA can bind in the large hydrophobic cavity of drug binding site I of sub-domain IIA and IIB, mainly by the hydrophobic interactions and also by hydrogen bond interactions. In which several cyclohexyl groups of BA are interacting with Phe(206), Arg(209), Ala(210), Ala(213), Leu(327), Gly(328), Leu(331), Ala(350), and Lys(351), residues of sub-domain IIA and IIB of HSA by hydrophobic interactions. Also, hydrogen bond interactions were observed between the hydroxyl (OH) group of BA with Phe(206) and Glu(354) of HSA, with hydrogen bond distances of 0.24 nm,0.28 nm respectively. Further, specifically, the molecular dynamics study makes an important contribution in understanding the effect of the binding of BA on conformational changes of HSA and the stability of the protein-drug complex system in aqueous solution. The root mean square deviation values of atoms in the free HSA molecule were calculated from 3000 ps to 5000 ps trajectory and the results were obtained as 0.72 +/- 0.036 nm and 0.81 +/- 0.032 nm for free HSA and HSA-BA, respectively. The radius of gyration (Rg) values of both unliganded HSA and HSA-BA were stabilized at 2.59 +/- 0.03 nm, 2.51 +/- 0.01 nm, respectively. Thus, this work may play an important role in the design of new BA inspired drugs with desired HSA binding affinity. PMID- 22076063 TI - Lentivirus-mediated RNA interference of E2F-1 suppresses Tca8113 cell proliferation. AB - In most types of human cancer, inactivation of pRb/E2F complexes occurs, and released E2Fs initiate transcription of genes required for cell cycle progression. Evidence reveals that phosphorylated pRb deregulates E2F-1, and the levels of E2F-1 expression can accurately predict prognosis of oral squamous cell carcinoma (OSCC). Paradoxically, numerous reports indicate that E2F-1 is also capable of inducing apoptosis under certain cellular circumstances. In the present study, lentivirus-mediated shRNA was used to downregulate endogenous E2F 1 expression in order to study the function of E2F-1 in the pRb/E2F-1 pathway in the OSCC cell line Tca8113, and to investigate the alteration of Tca8113 cells in proliferation and apoptosis. The data from real-time quantitative RT-PCR and Western blot analysis showed that E2F-1-shRNA led to the inhibition of endogenous E2F-1 mRNA and protein expression, and E2F-1 may be associated with proliferation and apoptosis pathways. Growth kinetics data showed that Tca8113-E2F-1-shRNA cells presented more active proliferation properties than Tca8113-NC cells, and flow cytometry data demonstrated that the percentages of cells in the G1 phase, G2 phase and undergoing apoptosis differed between groups. In conclusion, silencing of E2F-1 inhibits proliferation and induces apoptosis. E2F-1 may also be involved in multi-level regulation networks; therefore, its role in OSCC requires further clarification. PMID- 22076064 TI - Signaling via dopamine D1 and D3 receptors oppositely regulates cocaine-induced structural remodeling of dendrites and spines. AB - Repeated exposure to cocaine can induce persistent alterations in the brain. The structural remodeling of dendrites and dendritic spines is thought to play a critical role in cocaine addiction. We previously demonstrated that signaling via dopamine D1 and D3 receptors have opposite effects on cocaine-induced gene expression. Here, we show that cocaine-induced structural remodeling in the nucleus accumbens (NAc) and caudoputamen (CPu) is mediated by D1 receptors and inhibited by D3 receptors. In addition, chronic exposure to cocaine results in an altered number of asymmetric spine synapses via the actions of both D1 and D3 receptors. The contradictory effects of D1 and D3 receptor signaling on cocaine induced structural remodeling is associated with NMDA-receptor R1 subunit (NR1) phosphorylation, and is dependent upon the activation of extracellular signal regulated kinase (ERK). In addition, we found that D1 and D3 receptor signaling has contradictory effects upon the activation of the myocyte enhancer factor 2 (MEF2), which is involved in the dendritic remodeling after cocaine treatment. Together, these data suggest that dopamine D1 and D3 receptors differentially regulate the cocaine-induced structural remodeling of dendrites and spines via mechanisms involving the consecutive actions of NR1 phosphorylation, ERK activation, and MEF2 activity in the NAc and CPu. PMID- 22076065 TI - Early engraftment of G-CSF-primed allogeneic bone marrow transplantation in pediatric patients regardless of donor-recipient weight differences. AB - Harvesting sufficient progenitor cells from bone marrow (BM) for pediatric patients is a challenging process, especially from smaller donors. Growth factor administration to donors prior to harvest results in an enrichment of the graft and leads to early engraftment. A total of 41 patients received a human leukocyte antigen-identical sibling transplantation using granulocyte colony-stimulating factor (G-CSF)-primed BM. All donors received G-CSF 10 MUg/kg/day for 2 days prior to harvest. The median weight difference between donor and recipient was 3.9 kg (range, -29.8 to 32 kg), and the median number of CD34(+) cells harvested was 4.16 * 10(6)/kg (range, 1.17-31.9 * 10(6)/kg). The median time to neutrophil engraftment was 12 days (range, 10-27 days), and the time for platelet engraftment was 20 days (range, 12-64 days). The cumulative incidence of acute grade 2 to 3 graft-versus-host disease (GVHD) and chronic GVHD was 4.9% and 5.1%, respectively. An analysis according to the weight difference between donor and recipient showed there was no significant difference in harvested CD34(+) cell dose and in time required for engraftment between smaller and heavier donor recipients. G-CSF-primed BM allows successful engraftment and provides a valuable alternative to unstimulated BM and peripheral blood stem cells with good engraftment and tolerable GVHD even in patients with smaller donors. PMID- 22076066 TI - Laparoscopic versus open intersphincteric resection and coloanal anastomosis for low rectal cancer: intermediate-term oncologic outcomes. AB - OBJECTIVE: To compare the surgical outcome and intermediate oncological outcomes for laparoscopic versus open intersphincteric resection (ISR). BACKGROUND: Intersphincteric resection has been proposed as an alternative to abdominoperineal resection for selected low rectal cancer cases, but the oncological adequacy of laparoscopic ISR has not been established. METHODS: A total of 210 consecutive patients with low rectal cancer who underwent ISR between 1997 and 2009 in 2 institutions were evaluated retrospectively. Patients were classified into an open surgery (OS, n = 80) group and a laparoscopy (LAP, n = 130) group. The primary endpoint was 3-year disease-free survival. RESULTS: The major complication rates were similar in the LAP and OS groups (5.4% vs 3.8%, respectively; P = 0.428). However, the LAP group had a shorter hospital stay and time to bowel movement compared with the OS group. In the LAP group, operating time was 16 minutes shorter (P = 0.230) and intraoperative blood loss was less (P = 0.002). Median follow-up was 34 months (interquartile range: 20.0-42.5 months). The local recurrence rates were similar in the 2 groups (LAP, 2.6% vs OS, 7.7%; P = 0.184). The combined 3-year disease-free survival for all stages was 82.1% (95% CI: 73.7-90.2%) in the LAP group and 77.0% (95% CI: 66.9%-86.9%) in the OS group (P = 0.523). CONCLUSIONS: Laparoscopic ISR can be performed safely and offers a minimally invasive sphincter-sparing alternative. The oncological adequacy of laparoscopic ISR requires long-term follow-up data, but the intermediate-term outcomes seem equivalent to those achieved with OS. PMID- 22076067 TI - Comparison of International Consensus Guidelines versus 18-FDG PET in detecting malignancy of intraductal papillary mucinous neoplasms of the pancreas. AB - OBJECTIVE: To assess the reliability of the International Consensus Guidelines (ICG) and 18-fluorodeoxyglucose positron emission tomography (PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND: Since 2006 the ICG have been used to choose immediate surgery or surveillance for IPMN patients, but their low specificity increases the number of benign IPMNs that undergo resective surgery. PET has proved highly sensitive and specific in detecting malignancy in cystic neoplasms of the pancreas, including IPMNs. METHODS: Patients suspected with IPMNs of the pancreas seen at our Department from January 1989 to July 2010 were identified and classified as cases of main duct, mixed type and branch type IPMN. The indication for resection or surveillance was verified a posteriori for all patients according to the ICG. PET was considered positive for a Standardized Uptake Value >=2.5. Surveillance included clinical examination, laboratory tests, CA 19-9 serum levels, and computed tomography and/or magnetic resonance and magnetic resonance cholangiopancreatography every 6 months for 2 years and yearly thereafter. Endoscopic ultrasound was rarely performed. PET was repeated in clinically or radiologically suspect cases, or if tumor markers increased. RESULTS: Sixty-one main duct or mixed type and 101-branch type IPMNs were included in the study. A histological diagnosis was available for 81 of 162 patients, missing for 1 locally advanced IPMN, whereas 62 patients are under surveillance and it proved impossible to contact 18. Conservative surgery was performed in 16 of 68 patients with benign IPMNs. The sensitivity, specificity, positive and negative predictive value, and accuracy of the ICG in detecting malignancy were 93.2, 22.2, 59.4, 72.7, and 61.2, whereas for PET they were 83.3, 100, 100, 84.6, and 91.3. CONCLUSIONS: PET is more accurate than the ICG in distinguishing benign from malignant (invasive and noninvasive) IPMNs. Prophylactic IPMN resection in young patients fit for surgery should be guided by the ICG, whereas PET should be performed in older patients, cases at increased surgical risk, or when the feasibility of parenchyma-sparing surgery demands a reliable preoperative exclusion of malignancy. PMID- 22076068 TI - Does fundoplication really reduce deoxyribonucleic acid methylation of Barrett esophagus? PMID- 22076069 TI - Cognitive improvement after parathyroidectomy. PMID- 22076070 TI - The effect of the CMS national coverage decision on the performance and outcomes of bariatric surgery for medicare recipients in the U.S. PMID- 22076071 TI - Metallurgical phases and their magnetism at the interface of nanoscale MgB2/Fe layered structures. AB - We report on the characterization of metallurgical phases and their magnetism at the interfaces of nanoscale MgB(2)/Fe layered structures. MgB(2)/(57)Fe multilayers with varying layer thicknesses were prepared by vacuum deposition and investigated, before and after annealing by electrical resistance measurements, x ray diffraction and (57)Fe conversion-electron Mossbauer spectroscopy (CEMS) down to 5 K. Interfacial Fe-B phases, such as Fe(2)B, were identified by CEMS. A superparamagnetic-to-ferromagnetic transition is observed with increasing (57)Fe film thickness. Ultrahigh vacuum annealing at 500 degrees C of the multilayers leads to strong diffusion of Fe atoms into the boundary regions of the MgB(2) layers. MgB(2) in the as-grown multilayers is non-superconducting. Structural disorder and the effect of Fe interdiffusion contribute to the suppression of superconductivity in the MgB(2) films of all the as-grown multilayers and the thinner annealed multilayers. However, an annealed MgB(2)/(57)Fe/MgB(2) trilayer with thicker (500 A) MgB(2) layers is observed to be superconducting with an onset temperature of 25 K. At 5 K, the annealed trilayer can be conceived as being strongly chemically modulated, consisting of two partially Fe-doped superconducting MgB(2) layers separated by an interdiffused weakly magnetic Fe-B interlayer, which is characterized by a low hyperfine magnetic field B(hf) of ~11 T. This chemically modulated layer structure of the trilayer after annealing was verified by Rutherford backscattering. PMID- 22076072 TI - Acoustic analysis of voice in normal and high pitch phonation: a comparative study. AB - OBJECTIVES: Comparison of acoustic parameters of voice between normal and high pitch phonation in normal adults, and comparison between genders. PARTICIPANTS AND METHODS: A total of 48 normal laryngeal speakers were considered for this study. The acoustic parameters were analyzed using the Multi-Dimensional Voice Program. Descriptive statistics were used for analysis of the acoustic parameters across tasks and genders. Paired-samples t tests were used to compare measures between tasks. Independent-samples t tests were used to compare parameters between genders. RESULTS: Significant differences were found across tasks in the range of fundamental frequency and average fundamental frequency. Females showed a significant difference in the frequency perturbation measures - percent jitter and relative average perturbation, while males demonstrated a significant difference in the noise-to-harmonic ratio. While comparing mean differences between genders, significant differences were observed in fundamental frequency, range of the fundamental frequency, and smoothed pitch perturbation quotient during both phonation tasks. CONCLUSION: Comparison of acoustic parameters between normal and high pitch phonation would facilitate understanding the effect of high pitch phonation on voice parameters. Subsequently, this would help clinicians to focus on important acoustic parameters while assessing professional voice users who are at risk of developing voice problems. PMID- 22076073 TI - Improving data quality on low level mercury wastewater analysis. AB - In order to compare treatability test results evaluating low-level mercury (Hg) removal from oil refinery wastewater, improvements in Hg analytical methods were conducted at two US EPA certified analytical labs. The revisions in the analytical protocols improved Hg recoveries and hence enabled more reliable data interpretation and comparison for the specific wastewater tested. Nevertheless, significant differences between results from the two laboratories were identified in a split-sample experiment. PMID- 22076074 TI - Antitumor activity of chemoendocrine therapy in premenopausal and postmenopausal models with human breast cancer xenografts. AB - We examined the efficacy of chemoendocrine therapy using capecitabine as a chemotherapeutic agent in premenopausal and postmenopausal models with estrogen receptor (ER)-positive human breast cancer xenografts. Tamoxifen and letrozole were used as endocrine therapeutic agents for premenopausal and postmenopausal models, respectively. The antitumor activity of capecitabine in combination was significantly superior to either monotherapy treatment in both premenopausal (p<0.01) and postmenopausal (p<0.05) models. No increase in toxicity in terms of body weight loss was observed during treatment in either of the xenograft models. In the premenopausal model, the level of thymidine phosphorylase (TP), a key enzyme generating 5-FU from capecitabine, was upregulated (p<0.05) in tumors by tamoxifen but not by letrozole treatment in the postmenopausal model. The combination of 5'-deoxy-5-fluorouridine (5'-DFUR; an intermediate of capecitabine) with 4-hydroxytamoxifen (4-OHT; an active form of tamoxifen) or letrozole was also evaluated in vitro by using estrogen-responsive element (ERE) reporter gene assays aimed to model premenopausal and postmenopausal breast cancer. Both combinations decreased the number of estrogen-responding cells in a concentration-dependent manner and further analysis by isobolograms revealed a synergistic effect of the combination of 5'-DFUR with 4-OHT, and at least an additive effect of the combination of 5'-DFUR with letrozole. These results suggest that chemoendocrine therapy using capecitabine may be a useful treatment modality for patients with hormone-receptor-positive breast cancer, regardless of the menopausal status and should be explored in clinical trials. PMID- 22076075 TI - Evaluation of the anticancer activities of thioflavanone and thioflavone in human breast cancer cell lines. AB - This study investigated the anticancer effects of thioflavanone and thioflavone in the MCF-7, MDA-MB-231 and MDA-MB-453 human breast cancer cell lines. Cells were treated with either thioflavanone or thioflavone from 1 to 100 uM for 24 h, and their anti-proliferative activity and cytotoxicity was determined. Thioflavanone and thioflavone possessed similar anti-proliferative activities; their IC50 values were 62-89 and 74-128 uM, respectively, although the cytotoxicity of thioflavanone was significantly higher and occurred in a dose dependent manner. Taken together, these results suggest that thioflavanone significantly inhibits cellular proliferation with weak cytotoxicity to a greater extent than thioflavone, and induces apoptosis in human breast cancer cell lines. Moreover, thioflavanone, but not thioflavone, induces apoptosis via p53-dependent expression of Bax. PMID- 22076077 TI - Sexual attraction and trajectories of mental health and substance use during the transition from adolescence to adulthood. AB - Previous research suggests that sexual minority youth have poorer health-related outcomes than their heterosexual peers. The purpose of this study is to determine whether sexual orientation disparities in mental health and substance use increase, decrease, or remain the same during the transition from adolescence to adulthood. Data are from Waves 1-4 of the National Longitudinal Study of Adolescent Health (n = 8,322; 55% female). Respondents were in grades 7-12 at Wave 1 and aged 24-32 at Wave 4. Latent growth curve modeling is used to compare the mental health and substance use trajectories of youth who consistently report heterosexual attraction versus those who consistently report lesbian, gay, or bisexual (LGB) attraction, those who report a transition to LGB attraction, and those who report a transition to heterosexual attraction. Among women and men, sexual orientation disparities in depressive symptoms and suicidal thoughts persist, but do not increase, during the transition from adolescence to adulthood. The same pattern is observed for disparities in smoking, heavy drinking, and marijuana use among women. Among men, disparities in substance use are only observed between those who report consistent heterosexual attraction and those who transition to heterosexual attraction. Disparities between these groups persist over time for heavy drinking and marijuana use but decrease over time for smoking. While this study finds evidence of numerous disparities in mental health and substance use outcomes during adolescence and young adulthood, particularly among young women, there is no indication that these disparities get larger over time. PMID- 22076078 TI - Container molecules based on imine type ligands. AB - This chapter will give a short overview about container molecules, their synthesis and possible applications. The main focus is on those which are based on imine type ligands. These containers can be used for example for guest exchange, gas separation, as chemical sensors or for the stabilisation of white phosphorus under water. The described cages have wide openings or tightly closed ones. For one cage the reversible opening and closing is also described. PMID- 22076076 TI - Biodistribution and radiation dosimetry of the serotonin 5-HT6 ligand [11C]GSK215083 determined from human whole-body PET. AB - PURPOSE: We measured the whole-body distribution of IV-injected [11C]GSK215083, a new 5-HT6 antagonist PET tracer, as a function of time in adult subjects, in order to determine the radiation exposure. PROCEDURES: After injection with a single bolus of [11C]GSK215083 (range 330-367 MBq; mean 346 MBq), PET emission data were acquired for approximately 120 min in six subjects (three males and three females). Five organs were identified as exhibiting uptake above background. For these, regions of interest were delineated on emission images, and time-activity curves (TAC) generated. Residence times were calculated as the area under the curve of the TAC, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using the computer program OLINDA/EXM 1.0. RESULTS: The mean effective dose averaged over both males and females (deviation) was estimated to be 7.7 +/- 1.0 MUSv/MBq (male 7.0 +/- 0.4; female 8.5 +/- 0.6). For the effective dose equivalent, the corresponding values are 7.8 +/- 1.2 MUSv/MBq (male 6.8 +/- 0.5; female 8.9 +/- 0.1). The organ receiving the highest dose was the lung, with an average equivalent dose of 25.6 +/- 6.9 MUSv/MBq (male 20.8 +/- 5.6; female 30.4 +/- 4.4). CONCLUSION: The estimated radiation dose for [11C]GSK215083 is consistent with those for other neuroreceptor ligands labeled with carbon-11. The somewhat higher dose estimate for females compared to males may reflect the difference in observed residence times and representative differences in the male and female phantoms used for dosimetry calculations. Based on conventionally accepted dose limits, [11C]GSK215083 may be used for multiple PET scans in the same subject. PMID- 22076079 TI - Extracellular chaperones. AB - The maintenance of the levels and correct folding state of proteins (proteostasis) is a fundamental prerequisite for life. Life has evolved complex mechanisms to maintain proteostasis and many of these that operate inside cells are now well understood. The same cannot yet be said of corresponding processes in extracellular fluids of the human body, where inappropriate protein aggregation is known to underpin many serious diseases such as Alzheimer's disease, type II diabetes and prion diseases. Recent research has uncovered a growing family of abundant extracellular chaperones in body fluids which appear to selectively bind to exposed regions of hydrophobicity on misfolded proteins to inhibit their toxicity and prevent them from aggregating to form insoluble deposits. These extracellular chaperones are also implicated in clearing the soluble, stabilized misfolded proteins from body fluids via receptor-mediated endocytosis for subsequent lysosomal degradation. Recent work also raises the possibility that extracellular chaperones may play roles in modulating the immune response. Future work will better define the in vivo functions of extracellular chaperones in proteostasis and immunology and pave the way for the development of new treatments for serious diseases. PMID- 22076080 TI - The beauty of chemistry in the words of writers and in the hands of scientists. AB - Chemistry is a central science because all the processes that sustain life are based on chemical reactions, and all things that we use in everyday life are natural or artificial chemical compounds. Chemistry is also a fantastic world populated by an unbelievable number of nanometric objects called molecules, the smallest entities that have distinct shapes, sizes, and properties. Molecules are the words of matter. Indeed, most of the other sciences have been permeated by the concepts of chemistry and the language of molecules. Like words, molecules contain specific pieces of information that are revealed when they interact with one another or when they are stimulated by photons or electrons. In the hands of chemists, molecules, particularly when they are suitably combined or assembled to create supramolecular systems, can play a variety of functions, even more complex and more clever than those invented by nature. The wonderful world of chemistry has inspired scientists not only to prepare new molecules or investigate new chemical processes, but also to create masterpieces. Some nice stories based on chemical concepts (1) show that there cannot be borders on the Earth, (2) underline that there is a tight connection among all forms of matter, and (3) emphasize the irreplaceable role of sunlight. PMID- 22076081 TI - Inner and outer beauty. AB - Symmetry and pattern are precious forms of beauty that can be appreciated on both the macroscopic and molecular scales. Crystallographers have long appreciated the intimate connections between symmetry and molecular structure, reflected in their appreciation for the artwork of Escher. This admiration has been applied in the design of highly symmetrical coordination compounds. Two classes of materials are discussed: extended coordination arrays and discrete supramolecular assemblies. Extended coordination polymers have been implemented in gas separation and storage due to the remarkably porosity of these materials, aided by the ability to design ever-larger inner spaces within these frameworks. In the case of discrete symmetrical structures, defined inner and outer space present a unique aesthetic and chemical environment. The consequent host-guest chemistry and applications in catalysis are discussed. PMID- 22076082 TI - New directions in electron paramagnetic resonance spectroscopy on molecular nanomagnets. AB - Recent developments and results in the area of electron paramagnetic resonance (EPR) in molecular nanomagnetism are reviewed. Emphasis is placed on unconventional measurement methods, such as frequency-domain magnetic resonance spectroscopy, interferometer-based Fourier-transform, terahertz spectroscopy, and terahertz time-domain spectroscopy. In addition, different methods to investigate EPR by monitoring the change in magnetization or magnetic torque in the presence of microwave radiation are discussed. Finally, an overview is given of application of pulse EPR in investigations of molecular nanomagnets. PMID- 22076083 TI - Acute effects of verbal feedback on upper-body performance in elite athletes. AB - Argus, CK, Gill, ND, Keogh, JWL, and Hopkins, WG. Acute effects of verbal feedback on upper-body performance in elite athletes. J Strength Cond Res 25(12): 3282-3287, 2011-Improved training quality has the potential to enhance training adaptations. Previous research suggests that receiving feedback improves single effort maximal strength and power tasks, but whether quality of a training session with repeated efforts can be improved remains unclear. The purpose of this investigation was to determine the effects of verbal feedback on upper-body performance in a resistance training session consisting of multiple sets and repetitions in well-trained athletes. Nine elite rugby union athletes were assessed using the bench throw exercise on 4 separate occasions each separated by 7 days. Each athlete completed 2 sessions consisting of 3 sets of 4 repetitions of the bench throw with feedback provided after each repetition and 2 identical sessions where no feedback was provided after each repetition. When feedback was received, there was a small increase of 1.8% (90% confidence limits, +/-2.7%) and 1.3% (+/-0.7%) in mean peak power and velocity when averaged over the 3 sets. When individual sets were compared, there was a tendency toward the improvements in mean peak power being greater in the second and third sets. These results indicate that providing verbal feedback produced acute improvements in upper-body power output of well-trained athletes. The benefits of feedback may be greatest in the latter sets of training and could improve training quality and result in greater long-term adaptation. PMID- 22076084 TI - Maximal lactate steady-state independent of recovery period during intermittent protocol. AB - Barbosa, LF, de Souza, MR, Correa Carita, RA, Caputo, F, Denadai, BS, and Greco, CC. Maximal lactate steady-state independent of recovery period during intermittent protocol. J Strength Cond Res 25(12): 3385-3390, 2011-The purpose of this study was to analyze the effect of the measurement time for blood lactate concentration ([La]) determination on [La] (maximal lactate steady state [MLSS]) and workload (MLSS during intermittent protocols [MLSSwi]) at maximal lactate steady state determined using intermittent protocols. Nineteen trained male cyclists were divided into 2 groups, for the determination of MLSSwi using passive (VO(2)max = 58.1 +/- 3.5 ml.kg.min; N = 9) or active recovery (VO(2)max = 60.3 +/- 9.0 ml.kg.min; N = 10). They performed the following tests, in different days, on a cycle ergometer: (a) Incremental test until exhaustion to determine (VO(2)max and (b) 30-minute intermittent constant-workload tests (7 * 4 and 1 * 2 minutes, with 2-minute recovery) to determine MLSSwi and MLSS. Each group performed the intermittent tests with passive or active recovery. The MLSSwi was defined as the highest workload at which [La] increased by no more than 1 mmol.L between minutes 10 and 30 (T1) or minutes 14 and 44 (T2) of the protocol. The MLSS (Passive-T1: 5.89 +/- 1.41 vs. T2: 5.61 +/- 1.78 mmol.L) and MLSSwi (Passive T1: 294.5 +/- 31.8 vs. T2: 294.7 +/- 32.2 W; Active-T1: 304.6 +/- 23.0 vs. T2: 300.5 +/- 23.9 W) were similar for both criteria. However, MLSS was lower in T2 (4.91 +/- 1.91 mmol.L) when compared with in T1 (5.62 +/- 1.83 mmol.L) using active recovery. We can conclude that the MLSSwi (passive and active conditions) was unchanged whether recovery periods were considered (T1) or not (T2) for the interpretation of [La] kinetics. In contrast, MLSS was lowered when considering the active recovery periods (T2). Thus, shorter intermittent protocols (i.e., T1) to determine MLSSwi may optimize time of the aerobic capacity evaluation of well trained cyclists. PMID- 22076085 TI - The effects of adding different whole-body vibration frequencies to preconditioning exercise on subsequent sprint performance. AB - Ronnestad, BR and Ellefsen, S. The effects of adding different whole-body vibration frequencies to preconditioning exercise on subsequent sprint performance. J Strength Cond Res 25(12): 3306-3310, 2011-The phenomenon postactivation potentiation can possibly be used to acutely improve sprint performance. The purpose of this study was to investigate the effect of adding whole-body vibration (WBV) to body-loaded half-squats, performed as preconditioning activity to the 40-m sprint test. Nine male amateur soccer players performed 1 familiarization session and 6 separate test sessions. Each session included a standardized warm-up followed by 1 of the after preconditioning exercises: 30-seconds of half-squats with WBV at either 50 or 30 Hz or half-squats without WBV. The 40-m sprint was performed 1 minute after the preconditioning exercise. For each subject, each of the 3 protocols was repeated twice on separate days in a randomized order. Mean values were used in the statistical analysis. Performing the preconditioning exercise with WBV at a frequency of 50 Hz resulted in a superior 40-m sprint performance compared to preconditioning exercise without WBV (5.48 +/- 0.19 vs. 5.52 +/- 0.21 seconds, respectively, p < 0.05). There was no difference between preconditioning exercise with WBV at a frequency of 30 Hz and the no-WBV condition. In conclusion, preconditioning exercise performed with WBV at 50 Hz seems to enhance 40-m sprint performance in recreationally trained soccer players. The present findings suggest that coaches can incorporate such exercise into the warm-up to improve sprint performance or the quality of the sprint training. PMID- 22076086 TI - The acute potentiating effects of back squats on athlete performance. AB - Crewther, BT, Kilduff, LP, Cook, CJ, Middleton, MK, Bunce, PJ, and Yang, G-Z. The acute potentiating effects of back squats on athlete performance. J Strength Cond Res 25(12): 3319-3325, 2011-This study examined the acute potentiating effects of back squats on athlete performance with a specific focus on movement specificity and the individual timing of potentiation. Nine subelite male rugby players performed 3 protocols on separate occasions using a randomized, crossover, and counterbalanced design. Each protocol consisted of performance testing before a single set of 3 repetition maximum (3RM) back squats, followed by retesting at ~15 seconds, 4, 8, 12, and 16 minutes. The 3 tests were countermovement jumps (CMJs), sprint performance (5 and 10 m), and 3-m horizontal sled pushes with a 100-kg load. Relationships between the individual changes in salivary testosterone and cortisol concentrations and performance were also examined. The 3RM squats significantly (p < 0.001) improved CMJ height at 4 (3.9 +/- 1.9%), 8 (3.5 +/- 1.5%), and 12 (3.0 +/- 1.4%) minutes compared with baseline values, but no temporal changes in sprinting and sled times were identified. On an individual level, the peak relative changes in CMJ height (6.4 +/- 2.1%, p < 0.001) were greater than the 3-m sled (1.4 +/- 0.6%), 5-m (2.6 +/- 1.0%), and 10-m sprint tests (1.8 +/- 1.0%). In conclusion, a single set of 3RM squats was found effective in acutely enhancing CMJ height in the study population, especially when the recovery period was individualized for each athlete. The study results also suggest that the potentiating effects of squats may exhibit some degree of movement specificity, being greater for those exercises with similar movement patterns. The current findings have practical implications for prescribing warm up exercises, individualizing training programs, and for interpreting postactivation potentiation research. PMID- 22076087 TI - Aerobic capacities and anthropometric characteristics of elite female soccer players. AB - Ingebrigtsen, J, Dillern, T, and Shalfawi, SAI. Aerobic capacities and anthropometric characteristics of elite female soccer players. J Strength Cond Res 25(12): 3352-3357, 2011-This study investigated aerobic capacities and anthropometric characteristics within a group of 29 elite female soccer players. The purpose was to identify and establish aerobic capacities and anthropometric characteristics for these players and to look for possible positional differences between keepers, defenders, midfielders, and attackers. We did this by measuring standard anthropometrical variables and maximal oxygen (VO(2)max) and anaerobic threshold (AT). One-way analysis of variance revealed no significant differences among anthropometric or physiological variables. However, a trend (p = 0.062) toward positional differences was found within running speed at AT. A subsequent Tukey post hoc test showed differences (p = 0.04) between keepers and defenders, with the latter running faster (~1.7 km.h) at AT. The present results suggest that few anthropometric and physiological differences exist between playing positions in elite female soccer players. Furthermore, the current results indicate that present elite players' physiological characteristics are similar to those previously shown, despite the rapid changes of the female soccer game. Based on well-established knowledge that different playing positions within a soccer team ought to have distinct capacities, we recommend regular testing programs to be able to construct and implement tailored training programs for players' physical capacities with respect to the demands of their playing positions. PMID- 22076088 TI - Fatiguing upper body aerobic exercise impairs balance. AB - Douris, PC, Handrakis, JP, Gendy, J, Salama, M, Kwon, D, Brooks, R, Salama, N, and Southard, V. Fatiguing upper body aerobic exercise impairs balance. J Strength Cond Res 25(12): 3299-3305, 2011-There are many studies that have examined the effects of selectively fatiguing lower extremity muscle groups with various protocols, and they have all shown to impair balance. There is limited research regarding the effect of fatiguing upper extremity exercise on balance. Muscle fiber-type recruitment patterns may be responsible for the difference between balance impairments because of fatiguing aerobic and anaerobic exercise. The purpose of our study was to investigate the effect that aerobic vs. anaerobic fatigue, upper vs. lower body fatigue will have on balance, and if so, which combination will affect balance to a greater degree. Fourteen healthy subjects, 7 men and 7 women (mean age 23.5 +/- 1.7 years) took part in this study. Their mean body mass index was 23.6 +/- 3.2. The study used a repeated-measures design. The effect on balance was documented after the 4 fatiguing conditions: aerobic lower body (ALB), aerobic upper body (AUB), anaerobic lower body, anaerobic upper body (WUB). The aerobic conditions used an incremental protocol performed to fatigue, and the anaerobic used the Wingate protocol. Balance was measured as a single-leg stance stability score using the Biodex Balance System. A stability score for each subject was recorded immediately after each of the 4 conditions. A repeated measures analysis of variance with the pretest score as a covariate was used to analyze the effects of the 4 fatiguing conditions on balance. There were significant differences between the 4 conditions (p = 0.001). Post hoc analysis revealed that there were significant differences between the AUB, mean score 4.98 +/- 1.83, and the WUB, mean score 4.09 +/- 1.42 (p = 0.014) and between AUB and ALB mean scores 4.33 +/- 1.40 (p = 0.029). Normative data for single-leg stability testing for this age group are 3.9 +/- 1.9. Higher scores reflect greater balance deficits. The AUB condition produced the greatest balance deficit. Our data provide evidence of the important role of the upper body in maintaining unilateral standing balance and supports its inclusion as part of rehabilitation and training protocols designed to improve balance. PMID- 22076089 TI - Validity and reliability of agility tests in junior Australian football players. AB - Young, W, Farrow, D, Pyne, D, McGregor, W, and Handke, T. Validity and reliability of agility tests in junior Australian football players. J Strength Cond Res 25(12): 3399-3403, 2011-The importance of sport-specific stimuli in reactive agility tests (RATs) compared to other agility tests is not known. The purpose of this research was to determine the validity and reliability of agility tests. Fifty junior Australian football players aged 15-17 years, members of either an elite junior squad (n = 35) or a secondary school team (n = 15), were assessed on a new RAT that involved a change of direction sprint in response to the movements of an attacking player projected in life size on a screen. These players also underwent the planned Australian Football League agility test, and a subgroup (n = 13) underwent a test requiring a change of direction in response to a left or right arrow stimulus. The elite players were significantly better than the school group players on the RAT (2.81 +/- 0.08 seconds, 3.07 +/- 0.12 seconds; difference 8.5%) but not in the arrow stimulus test or planned agility test. The data were log transformed and the reliability of the new RAT estimated using typical error (TE) expressed as a coefficient of variation. The TE for the RAT was 2.7% (2.0-4.3, 90% confidence interval) or 0.07 seconds (0.5-1.0), with an intraclass correlation coefficient (ICC) of 0.33. For the test using the arrow stimulus, the TE was 3.4% (2.4-6.2), 0.09 (0.06-0.15) seconds, and ICC was 0.10. The sport-specific stimulus provided by the new RAT is a crucial component of an agility test; however, adoption of the new RAT for routine testing is likely to require more accessible equipment and several familiarization trials to improve its reliability. PMID- 22076090 TI - Effects of unilateral and bilateral plyometric training on power and jumping ability in women. AB - Makaruk, H, Winchester, JB, Sadowski, J, Czaplicki, A, and Sacewicz, T. Effects of unilateral and bilateral plyometric training on power and jumping ability in women. J Strength Cond Res 25(12): 3311-3318, 2011-The purpose of this study was to examine the effects of unilateral and bilateral plyometric exercise on peak power and jumping performance during different stages of a 12-week training and detraining in women. Forty-nine untrained but physically active female college students were randomly assigned to 1 of 3 groups: unilateral plyometric group (n = 16), bilateral plyometric group (BLE; n = 18), and a control group (n = 15). Peak power and jumping ability were assessed by means of the alternate leg tests (10-second Wingate test and 5 alternate leg bounds), bilateral leg test (countermovement jump [CMJ]) and unilateral leg test (unilateral CMJ). Performance indicators were measured pretraining, midtraining, posttraining, and detraining. Differences between dependent variables were assessed with a 3 * 4 (group * time) repeated analysis of variance with Tukey's post hoc test applied where appropriate. Effect size was calculated to determine the magnitude of significant differences between the researched parameters. Only the unilateral plyometric training produced significant (p < 0.05) improvement in all tests from pretraining to midtraining, but there was no significant (p < 0.05) increase in performance indicators from midtraining to posttraining. The BLE group significantly (p < 0.05) improved in all tests from pretraining to posttraining and did not significantly (p > 0.05) decrease power and jumping ability in all tests during detraining. These results suggest that unilateral plyometric exercises produce power and jumping performance during a shorter period when compared to bilateral plyometric exercises but achieved performance gains last longer after bilateral plyometric training. Practitioners should consider the inclusion of both unilateral and bilateral modes of plyometric exercise to elicit rapid improvements and guard against detraining. PMID- 22076091 TI - Physical and performance characteristics of Japanese division 1 collegiate football players. AB - Iguchi, J, Yamada, Y, Ando, S, Fujisawa, Y, Hojo, T, Nishimura, K, Kuzuhara, K, Yuasa, Y, and Ichihashi, N. Physical and performance characteristics of Japanese division 1 collegiate football players. J Strength Cond Res 25(12): 3368-3377, 2011-This study aimed to establish the physical and performance characteristics of football players in the Japanese Division 1 collegiate football program and perform a comparison of these characteristics between Japanese (n = 208) and US Division 1 football players (n = 797). The following comparisons were made: (a) between a higher-ranked university team vs. a lower-ranked university team in Japan, (b) between different playing positions in Japan, (c) between starters and nonstarters in Japan, and (d) between playing positions in Japan vs. those in the United States. The results of this study suggest that players in the higher ranked university team were heavier, stronger in back squat, jumped higher, and had greater power than those on the lower-ranked team. Furthermore, linemen were generally characterized by larger size, greater strength, and more fat as compared with backs. On the other hand, backs tended to be faster, smaller in physical size, have higher vertical jump height, and show greater relative strength than linemen did. Starters were taller, heavier, stronger, had more powerful, and more fat-free mass than nonstarters. Finally, our results revealed that players in the United States were superior to players in Japan in all body status comparisons (p < 0.01). This study revealed that performance and superior body composition are essential for the success of a football player. Power and strength seem to be key factors in defining good football performance. PMID- 22076092 TI - Test-retest reliability for hitting accuracy tennis test. AB - Strecker, E, Foster, EB, and Pascoe, DD. Test-retest reliability for hitting accuracy tennis test. J Strength Cond Res 25(12): 3501-3505, 2011-The purpose of this investigation was to assess a test-retest reliability of the hitting accuracy tennis test (HATT). Twelve National Collegiate Athletic Association (NCAA) division I tennis players (4 men and 8 women) volunteered to participate in this investigation. Skill tests consisted of 15 consecutive ground strokes in all 4 directions (forehand [FH] and backhand [BH]; crosscourt and up the line) with not >1 minute between directions. The court was divided into 12 areas, and each area was assigned a value according to a grid system based on offensive, defensive, and neutral shots ranging from 1 point to 6 points. Total score, unforced errors, and shot index (total number of shots that landed on optimal performance areas 5 and 6 minus total number of unforced errors) were used for statistical analysis. The order of shot direction was randomized between participants and trials. The analysis of variance with repeated measures (p value <= 0.05) of this investigation showed no statistical difference between trials on any of the measurements. The results also suggest that division I level tennis players have the ability to hit accurately specific targets on a tennis court using either FH or BH with minimal daily variation. Therefore, we conclude that the HATT for trained tennis athletes is a simple, reliable, and accurate assessment tool to measure tennis skill performance based on accuracy. The HATT is also an easy, inexpensive training device that coaches can use to monitor players development. PMID- 22076093 TI - The yo-yo intermittent recovery test in junior basketball players according to performance level and age group. AB - The aim of this study was to evaluate the Yo-Yo Intermittent Recovery Test Level 1 (Yo-Yo IR1) ability to discriminate between elite, subelite junior basketball players, and a group of nonathletic healthy male athletes at 3 different age groups (U-14 to U-17). In a cross-sectional design, 119 age-matched participants spread over 3 groups, elite (n = 46), subelite (n = 42) junior basketball players, and nonathletic healthy male athletes (n = 31), were evaluated over a 5 week period. The participants undertook 2 familiarization trials of the Yo-Yo test performance and 3 test sessions on an indoor basketball court. When controlling for the effect of the participants' body mass, the results showed that elite athletes had a significantly higher Yo-Yo performance compared with the subelite athletes (1,271 +/- 385 vs. 861 +/- 428 m; p < 0.0017; effect size [ES] 1.0 +/- 0.35) and the nonathletic group (1,271 +/- 385 vs. 738 +/- 345 m; p < 0.0017; ES 1.45 +/- 0.38). No statistical differences (p > 0.0017; ES from 0.02 to 0.39) were noted between participants' performance levels across age groups. Typical between-performance levels and -age groups differences in the Yo-Yo IR1 were observed. However, when controlling for the effect of the participants' body mass, this study demonstrates that the Yo-Yo test is accurate only to discriminate elite junior basketball players but cannot be used to differentiate the basketball-specific aerobic performance for age. PMID- 22076094 TI - Rocker-bottom, profile-type shoes do not increase lower extremity muscle activity or energy cost of walking. AB - The purpose of this study was to determine if wearing rocker-bottom shoes with compliant midsoles (RB) influences muscle activity and metabolic cost of walking. Furthermore, we sought to determine if weight differences between shod conditions accounted for any potential change. Twenty-eight subjects (17 women, 11 men, age 22.8 +/- 6.6 years; weight 72 +/- 20 kg; height 170 +/- 6.7 cm; percent body fat 23.0 +/- 11.7) walked on a treadmill (0% grade) for 10 minutes at a self-selected speed plus 10% (1.3 +/- 0.2 m.s) in each of the following laboratory-provided shoes: flat-bottomed shoe (W), flat-bottomed shoe weight-matched to RB (WM), and RB. Muscle activity of the right side biceps femoris (BF), rectus femoris (RF), gastrocnemius (GA), and tibalis anterior (TA) was recorded for 30 seconds at the beginning, middle, and ending of the 10-minute walk using an electromyography (EMG) system. The average (AVG) and root mean square (RMS) were calculated from full-wave rectified EMG data at each interval. The rate of oxygen consumption (V[Combining Dot Above]O2) was measured for 10 minutes during each condition. A 3 (shoe) * 3 (time) repeated-measures analysis of variance (ANOVA) was used to compare each EMG-dependent variable (AVG and RMS EMG of each muscle), and repeated measures ANOVA was used to test V[Combining Dot Above]O2. Muscle activity (for any muscle) was not influenced by the interaction of shoe and time (p > 0.05). The AVG and RMS for RF, BF, and GA, including V[Combining Dot Above]O2, were not different among shod conditions (W: 9.7 +/- 0.6 ml.kg.min; WM: 10.0 +/- 0.5 ml.kg.min; RB: 10.1 +/- 0.5 ml.kg.min), whereas TA AVG and RMS were lower during RB (p < 0.05). It seems that there is no increase in muscle activity or metabolic cost while wearing RB beyond the flat-bottomed shoe despite there being the rocker-profile design and mass differences. PMID- 22076095 TI - Changes in strength over a 2-year period in professional rugby union players. AB - The purpose of this study was to assess the magnitude of upper and lower body strength changes in highly trained professional rugby union players after 2 years of training. An additional purpose was to examine if the changes in strength were influenced by the starting strength level, lean mass index (LMI), or chronological age. This longitudinal investigation tracked maximal strength and body composition over 3 consecutive years in 20 professional rugby union athletes. Maximal strength in the bench press and back squat and body composition was assessed during preseason resistance training sessions each year. The athletes completed a very rigorous training program throughout the duration of this study consisting of numerous resistance, conditioning and skills training sessions every week. The primary findings of this study were as follows: (a) Maximal upper and lower body strength was increased by 6.5-11.5% after 2 years of training (p = 0.000-0.002 for bench press; p = 0.277-0.165 for squat); (b) magnitude of the improvement was negatively associated with initial strength level (r = -0.569 to -0.712, p <= 0.05); (c) magnitude of improvement in lower body maximal strength was positively related to the change in LMI (an indicator of hypertrophy; r = 0.692-0.880, p <= 0.05); and (d) magnitude of improvement was not associated with the age of professional rugby union athletes (r = -0.068 to 0.345). It appears particularly important for training programs to be designed for continued muscle hypertrophy in highly trained athletes. Even in professional rugby union athletes, this must be achieved in the face of high volumes of aerobic and skills training if strength is to be increased. PMID- 22076096 TI - Physical characteristics and physiological attributes of female volleyball players--the need for individual data. AB - The purpose of this study was twofold: (a) to profile physical characteristics and physiological attributes of adolescent and adult Greek female volleyball players (n = 61) who were members of the A (the best league for female volleyball players) and B (the second-best league for female volleyball players) Series clubs in Greece and (b) to examine the intraindividual variability among these players in all physical and physiological measurements that were undertaken in the study. The participants were divided into 3 age groups--under 14, 14-18, and over 18 years. They underwent a series of physical (e.g., height, body mass, and percentage of body fat) and physiological (e.g., aerobic profile, flexibility, and vertical jumping ability) tests. Three main findings emerged from the data analysis: (a) differences in physical characteristics and physiological attributes existed between the 3 age groups. For example, fat-free mass was lower in players under the age of 14 years (41.57 +/- 6.06 kg) compared with that in players between the ages of 14-18 years (50.24 +/- 6.96 kg) and players over the age of 18 years (52.03 +/- 3.39 kg). In addition, the relative peak power as measured in the Wingate Anaerobic Test was the highest in the over-18 group (9.72 +/- 0.65 W.kg), lower in the 14-18 group (8.95 +/- 0.7), and the lowest in the under-14 group (8.32 +/- 0.78 W.kg), (b) large intraindividual variability existed in most physical characteristics and physiological attributes measured in the study, and (c) the intraindividual variability was observed in all the 3 groups. These findings emphasize the need for coaches to examine the intraindividual variability within the players on their teams and to use this information when designing training programs and strength and conditioning programs. PMID- 22076097 TI - Work volume and strength training responses to resistive exercise improve with periodic heat extraction from the palm. AB - Body core cooling via the palm of a hand increases work volume during resistive exercise. We asked: (a) "Is there a correlation between elevated core temperatures and fatigue onset during resistive exercise?" and (b) "Does palm cooling between sets of resistive exercise affect strength and work volume training responses?" Core temperature was manipulated by 30-45 minutes of fixed load and duration treadmill exercise in the heat with or without palm cooling. Work volume was then assessed by 4 sets of fixed load bench press exercises. Core temperatures were reduced and work volumes increased after palm cooling (Control: Tes = 39.0 +/- 0.1 degrees C, 36 +/- 7 reps vs. Cooling: Tes = 38.4 +/- 0.2 degrees C, 42 +/- 7 reps, mean +/- SD, n = 8, p < 0.001). In separate experiments, the impact of palm cooling on work volume and strength training responses were assessed. The participants completed biweekly bench press or pull up exercises for multiple successive weeks. Palm cooling was applied for 3 minutes between sets of exercise. Over 3 weeks of bench press training, palm cooling increased work volume by 40% (vs. 13% with no treatment; n = 8, p < 0.05). Over 6 weeks of pull-up training, palm cooling increased work volume by 144% in pull-up experienced subjects (vs. 5% over 2 weeks with no treatment; n = 7, p < 0.001) and by 80% in pull-up naive subjects (vs. 20% with no treatment; n = 11, p < 0.01). Strength (1 repetition maximum) increased 22% over 10 weeks of pyramid bench press training (4 weeks with no treatment followed by 6 weeks with palm cooling; n = 10, p < 0.001). These results verify previous observations about the effects of palm cooling on work volume, demonstrate a link between core temperature and fatigue onset during resistive exercise, and suggest a novel means for improving strength and work volume training responses. PMID- 22076099 TI - Relationship between measures of balance and strength in middle-aged adults. AB - The purpose of this study was to investigate the relationship between variables of static and dynamic postural control as well as between isometric and dynamic muscle strength. A single-group design was used. Thirty-two middle-aged healthy adults (mean age: 56 +/- 4 years) performed measurements of static (unperturbed)/dynamic (perturbed) balance and of isometric (i.e., maximal isometric torque [MIT]; rate of torque development [RTD] of the plantar flexor)/dynamic (i.e., countermovement jump [CMJ] height and power) lower extremity muscle strength. No significant associations were observed between variables of static and dynamic postural control (r = +0.128-0.341, p > 0.05) and between measures of balance and strength (r = -0.189 to +0.316, p > 0.05). Significant positive correlations were detected between variables of isometric and dynamic strength ranging from r = +0.361 to +0.501 (p < 0.05). Further, simple regression analyses revealed that a 10% increase in the mean CMJ height (3.1 cm) was associated with 44.4 N.m and 118.4 N.m.s better MIT and RTD, respectively. The nonsignificant correlations between static and dynamic balance measures and between balance and strength variables imply that static and dynamic postural control and balance and strength are independent of each other and may have to be tested and trained complementarily. PMID- 22076098 TI - Lower extremity biomechanics during a regular and counterbalanced squat. AB - If the efficiency of human movement patterns could be improved using exercise, this could lead to more effective musculoskeletal disease-injury prevention and rehabilitation programs. It has been suggested that an efficient squat movement pattern emphasizes the use of the large hip extensors instead of the smaller knee extensors. The purpose of this study was to determine whether a counterbalanced squat (CBS) could produce a more hip-dominant and less knee-dominant squat movement pattern as compared with a regular squat (RS). There were 31 recreationally trained college-aged participants (15 male, 16 female) who performed 10 squats (5 CBS and 5 RS), while segment kinematics, ground reaction forces, and muscle (gluteus maximus [GM], quadriceps, hamstrings) electromyographic (EMG) activations were recorded. Peak sagittal plane net joint moments and joint ranges of motion at the hip, knee, and ankle joints along with peak and integrated EMG activation levels for all 3 muscles were compared using analysis of variance (squat type * sex). The results revealed that the CBS increased the hip joint moment and GM activation, while it decreased the knee joint moment and quadriceps activation as compared with the RS. Therefore, the CBS produces a more hip-dominant and less knee-dominant squat movement pattern and could be used in exercise programs aimed at producing more hip-dominant movement patterns. PMID- 22076100 TI - Effect of verbal instruction on muscle activity during the bench press exercise. AB - Recent research suggests that humans have some ability to selectively activate or relax some muscles during isometric or dynamic muscle actions without changing posture or position. This study sought to reveal whether trained athletes could isolate either the pectoral or triceps muscles, respectively, at different intensities when given verbal technique instruction. Eleven male Division III football players performed 3 sets of bench press at 50% 1-repetition max (1RM) and 80% 1RM while electromyographic (EMG) activity was recorded from the pectoralis major (PM), anterior deltoid (AD), and triceps brachii (TB). In the first set, the subjects performed the exercise without instruction. In the second set, the subjects were given verbal instructions to use only chest muscles. In the third set, the subjects were instructed to use only triceps muscles. Mean normalized root mean square EMG activity was calculated during 3 repetitions in each condition. Repeated-measures analysis of variance was used to detect differences from the preinstruction condition, with significance set to p <= 0.017 as indicated by a Bonferroni correction for multiple comparisons. During the 50% max lift with verbal instructions to focus on chest muscles, PM EMG activity increased by 22% over preinstruction activity (p = 0.005), whereas AD and TB activities were statistically unchanged. When the subjects were instructed to focus on only the triceps muscles, PM returned to baseline activity, whereas TB activity was increased by 26% (p = 0.005). When the lift was increased to 80% max, PM and AD activities were both increased with verbal instructions to use only chest muscles. The TB activity was unchanged during the 80% lifts, regardless of instructions. In conclusion, it is found that verbal technique instruction is effective in shifting muscle activity during a basic lift, but it may be less effective at higher intensities. PMID- 22076101 TI - Scapular muscle activity from selected strengthening exercises performed at low and high intensities. AB - A balanced level of muscle strength between the different parts of the scapular muscles is important in optimizing performance and preventing injuries in athletes. Emerging evidence suggests that many athletes lack balanced strength in the scapular muscles. Evidence-based recommendations are important for proper exercise prescription. This study determines scapular muscle activity during strengthening exercises for scapular muscles performed at low and high intensities (Borg CR10 levels 3 and 8). Surface electromyography (EMG) from selected scapular muscles was recorded during 7 strengthening exercises and expressed as a percentage of the maximal EMG. Seventeen women (aged 24-55 years) without serious disorders participated. Several of the investigated exercises press-up, prone flexion, one-arm row, and prone abduction at Borg 3 and press-up, push-up plus, and one-arm row at Borg 8-predominantly activated the lower trapezius over the upper trapezius (activation difference [Delta] 13-30%). Likewise, several of the exercises-push-up plus, shoulder press, and press-up at Borg 3 and 8-predominantly activated the serratus anterior over the upper trapezius (Delta18-45%). The middle trapezius was activated over the upper trapezius by one-arm row and prone abduction (Delta21-30%). Although shoulder press and push-up plus activated the serratus anterior over the lower trapezius (Delta22-33%), the opposite was true for prone flexion, one-arm row, and prone abduction (Delta16-54%). Only the press-up and push-up plus activated both the lower trapezius and the serratus anterior over the upper trapezius. In conclusion, several of the investigated exercises both at low and high intensities predominantly activated the serratus anterior and lower and middle trapezius, respectively, over the upper trapezius. These findings have important practical implications for exercise prescription for optimal shoulder function. For example, both workers with neck pain and athletes at risk of shoulder impingement (e.g., overhead sports) should perform push-up plus and press-ups to specifically strengthen the serratus anterior and lower trapezius. PMID- 22076102 TI - Achievement of VO2max criteria during a continuous graded exercise test and a verification stage performed by college athletes. AB - The purpose of this study was to determine the incidence of meeting specific VO2max criteria and to test the effectiveness of a VO2max verification stage in college athletes. Thirty-five subjects completed a continuous graded exercise test (GXT) to volitional exhaustion. The frequency of achieving various respiratory exchange ratio (RER) and age-predicted maximum heart rate (HRmax) criteria and a VO2 plateau within 2 and 2.2 ml.kg(-1).min(-1) (<2SD of the expected increase in VO2) were measured and tested against expected frequencies. After 10 minutes of active recovery, 10 subjects who did not demonstrate a plateau completed a verification stage performed at supramaximal intensity. From the GXT, the number of subjects meeting VO2max plateau was 5 (<=2 ml.kg(-1).min( 1)) and 7 (<=2.2 ml.kg(-1).min(-1)), RER criteria 34 (>=1.05), 32 (>=1.10), and 24 (>=1.15), HRmax criteria, 35 (<85%), 29 (<10 b.min(-1)) and 9 (HRmax). The VO2max and HRmax did not differ between GXT and the verification stage (53.6 +/- 5.6 vs. 55.5 +/- 5.6 ml.kg(-1).min(-1) and 187 +/- 7 vs. 187 +/- 6 b.min(-1)); however, the RER was lower during the verification stage (1.15 +/- 0.06 vs. 1.07 +/- 0.07, p = 0.004). Six subjects achieved a similar VO2 (within 2.2 ml.kg( 1).min(-1)), whereas 4 achieved a higher VO2 compared with the GXT. These data demonstrate that a continuous GXT limits the college athlete's ability to achieve VO2max plateau and certain RER and HR criteria. The use of a verification stage increases the frequency of VO2max achievement and may be an effective method to improve the accuracy of VO2max measurements in college athletes. PMID- 22076104 TI - A ras GTPase-activating protein-binding protein, TaG3BP, associated with the modulation of male fertility in a thermo-sensitive cytoplasmic male sterile wheat line. AB - Hybrid wheat development may contribute to higher, more stable yield and could result in greater food security for much of the world's growing population. YS type thermo-sensitive cytoplasmic male sterile (TCMS) wheat lines were developed for use in hybrid wheat breeding in China. To investigate the molecular mechanism of modulation of male fertility in the YS-type TCMS wheat lines, a ras GTPase activating protein-binding protein (TaG3BP) was examined. The deduced amino acid sequence encoded by TaG3BP was conserved in the sequenced genomes of Embryophyte. TaG3BP expression in the anthers of YS-type TCMS lines taken at the critical fertility reversion stage of pollen development from male fertile anthers was higher than that from male-sterile anthers, either by quantitative real-time PCR or by western blot analysis. Sequence analysis on the cDNA and genomic DNA of TaG3BP in three kinds of K-type CMS wheat lines and their maintainers indicated that there were no significant difference between the genes or in their 5' flanking sequences. The TaG3BP expression revealed by quantitative real-time RT PCR was lower in the young spikes of these CMS lines than that of their maintainers. This indicates that TaG3BP expression is associated with the modulation, from male-sterile to fertile, of the TCMS wheat line, and TaG3BP might be a key factor in the pathway responsible for the fertility reversion. PMID- 22076103 TI - Heterotrophic bacteria in drinking water distribution system: a review. AB - The microbiological quality of drinking water in municipal water distribution systems (WDS) depends on several factors. Free residual chlorine and/or chloramines are typically used to minimize bacterial recontamination and/or regrowth in WDS. Despite such preventive measures, regrowth of heterotrophic (HPC) and opportunistic bacteria in bulk water and biofilms has yet to be controlled completely. No approach has shown complete success in eliminating biofilms or HPC bacteria from bulk water and pipe surfaces. Biofilms can provide shelter for pathogenic bacteria and protect these bacteria from disinfectants. Some HPC bacteria may be associated with aesthetic and non-life threatening diseases. Research to date has achieved important success in understanding occurrence and regrowth of bacteria in bulk water and biofilms in WDS. To achieve comprehensive understanding and to provide efficient control against bacteria regrowth, future research on bacteria regrowth dynamics and their implications is warranted. In this study, a review was performed on the literature published in this area. The findings and limitations of these papers are summarized. Occurrences of bacteria in WDS, factors affecting bacteria regrowth in bulk water and biofilms, bacteria control strategies, sources of nutrients, human health risks from bacterial exposure, modelling of bacteria regrowth and methods of bacteria sampling and detection and quantification are investigated. Advances to date are noted, and future research needs are identified. Finally, research directions are proposed to effectively control HPC and opportunistic bacteria in bulk water and biofilms in WDS. PMID- 22076105 TI - Toxicogenomic comparison of multi-wall carbon nanotubes (MWCNTs) and asbestos. AB - Carbon nanotubes (CNTs) have specific properties, including electrical and thermal conductivity, great strength, and rigidity, that allow them to be used in many fields. However, this increasing contact with humans and the environment is also raising health and safety concerns. Thus, research on the safety of CNTs has attracted much interest, including a comparison of the toxic effects of asbestos and carbon nanotubes, due to their physical similarity of a high aspect ratio (length/diameter). Nonetheless, there has not yet been a toxicogenomic comparison. Therefore, to examine toxicogenomic effects, the 50% growth inhibition (GI(50)) concentration was determined for multi-wall carbon nanotubes (MWCNTs) and asbestos (crocidolite) and found to be approximately 0.0135 and 0.066%, respectively, in the case of 24-h treatment of normal human bronchial epithelia (NHBE) cells. Using these GI(50) concentrations, NHBE cells were then treated with MWCNTs and asbestos for 6 and 24 h, followed by a DNA microarray analysis. Among 31,647 genes, 1,201 and 1,252 were up-regulated by both asbestos and MWCNTs after 6 and 24 h of exposure, respectively. Meanwhile, 1,977 and 1,542 genes were down-regulated by both asbestos and MWNCTs after 6 and 24 h of exposure, respectively. In particular, the asbestos and MWCNTs both induced an over twofold up- and down-regulated expression of 12 mesothelioma-related genes and 22 lung cancer-related genes when compared with the negative control. Plus, the genes induced by the MWCNT exposure were expressed in the brain, lungs, epithelium, liver, and colon. PMID- 22076106 TI - Magnetic nanoparticles: an update of application for drug delivery and possible toxic effects. AB - Magnetic nanoparticles (MNPs) represent a subclass within the overall category of nanomaterials and are widely used in many applications, particularly in the biomedical sciences such as targeted delivery of drugs or genes, in magnetic resonance imaging, and in hyperthermia (treating tumors with heat). Although the potential benefits of MNPs are considerable, there is a distinct need to identify any potential toxicity associated with these MNPs. The potential of MNPs in drug delivery stems from the intrinsic properties of the magnetic core combined with their drug loading capability and the biomedical properties of MNPs generated by different surface coatings. These surface modifications alter the particokinetics and toxicity of MNPs by changing protein-MNP or cell-MNP interactions. This review contains current advances in MNPs for drug delivery and their possible organ toxicities associated with disturbance in body iron homeostasis. The importance of protein-MNP interactions and various safety considerations relating to MNP exposure are also addressed. PMID- 22076107 TI - Mechanistic study on liver tumor promoting effects of flutamide in rats. AB - Flutamide (FLU), a nonsteroidal anti-androgen, is used for the treatment of prostate cancer but is also a cytochrome P450 (CYP) 1A inducer. Some CYP1A inducers are known to exert hepatocellular tumor-promoting activities in rodents, and reactive oxygen species (ROS) produced by CYP1A1 induction via a metabolism of FLU is probably involved in the liver tumor promotion. In the present study, to clarify the possible liver tumor promoting effect of FLU, a two-stage liver carcinogenesis assay was performed using male F344 rats. Rats received an intraperitoneal (ip) injection of 200 mg/kg body weight of N-diethylnitrosamine (DEN) and fed a diet containing 0, 0.1 or 0.2% FLU for 6 weeks. After 2 weeks of DEN treatment, all rats were subjected to two-thirds partial hepatectomy. Animals were killed 8 weeks after ip injection of DEN. Immunohistochemically, the number and area of glutathione S-transferase placental form (GST-P)-positive foci significantly increased in the liver of rats given 0.2% FLU as compared with the control. Ki-67-positive cell ratio also increased in rats given FLU at both concentrations. ROS generation in the microsomal fraction and production of thiobarbituric acid-reactive substance [TBARS] and 8-hydroxy-2'-deoxyguanosine (8 OHdG) content in the liver did not increase in any of the FLU-treated groups. The results of microarray and real-time RT-PCR revealed that phase 1 drug metabolizing enzymes such as CYP1A1, Ugt1a61 and Nqo1 and phase II drug metabolizing enzymes such as Yc2, Akr1b7, Akr1b8, Akr1b10, Aldh1a1, Gpx2 and Me1 were up-regulated in rats treated with FLU. In addition, the MAPK pathway family related genes such as Prkcalpha, Mek1, Rafb, Myc, Mek2, Raf1 and Egfr were also up-regulated in FLU-treated groups. The results of the present study indicate that FLU is a CYP1A inducer but does not cause any production of microsomal ROS in the liver and suggest that microsomal ROS is not involved in the liver tumor promoting effect of FLU. PMID- 22076108 TI - Comparison of experimentally determined and mathematically predicted percutaneous penetration rates of chemicals. AB - The aim of the study was to evaluate the predictive potential of three different mathematical models for the percutaneous penetration of industrial solvents with respect to our experimental data. Percutaneous penetration rates (fluxes) from diffusion cell experiments of 11 chemicals were compared with fluxes predicted by mathematical models. The chemicals considered were three glycol ethers (2 butoxyethanol, diethylene glycol monobutyl ether and 1-ethoxy-2-propanol), three alcohols (ethanol, isopropanol and methanol), two glycols (ethylene glycol and 1,2-propanediol), one aromatic hydrocarbon (toluene) and two aromatic amines (aniline and o-toluidine). For the mathematical prediction of fluxes, models described by Fiserova-Bergerova et al. (Am J Ind Med 17:617-635 1990), Guy and Potts (Am J Ind Med 23:711-719 1993) and Wilschut et al. (Chemosphere 30:1275 1296 1995) were used. The molecular weights, octanol-water partition coefficients (LogP) and water solubilities of the compounds were obtained from a database for modelling. The fit between the mathematically predicted and experimentally determined fluxes was poor (R(2) = 0.04-0.29; linear regression). The flux differences ranged up to a factor of 412. For 4 compounds, the Guy and Potts model showed a closer fit with the experimental flux than the other models. The Wilschut et al. model showed a lower flux difference for 4 compounds as compared to experimental data than the models of Fiserova-Bergerova et al. and Guy and Potts. The Fiserova-Bergerova et al. model showed for 3 compounds a lower flux difference to experimental data than the other models. This study demonstrates large differences between mathematically predicted and experimentally determined fluxes. The percutaneous penetration as determined in diffusion cell experiments may be considerably overestimated as well as underestimated by mathematical models. Although the number of compounds in our comparison study is small, the results point out that none of the mathematical model has significant advantages. PMID- 22076109 TI - Balanced nursing report card. PMID- 22076110 TI - Alliance for Nursing Informatics pledge to support the Consumer eHealth Program. PMID- 22076111 TI - ANA pledges to help patients improve care through use of electronic health information: association joins national Consumer eHealth Program launch. PMID- 22076112 TI - Transforming nursing practice through technology and informatics. PMID- 22076114 TI - Comparison of monolisa HCV Ag/Ab ULTRA with two anti-HCV assays for the detection of HCV infection in hospital setting. AB - In this study, we compared the performance of three serological assays (Monolisa HCV Ag/Ab ULTRA, Innotest HCV Ab IV enzyme immunoassay--EIA, and Ortho HCV 3.0 enzyme-linked immunosorbent assay--ELISA) for the detection of HCV infection. Ninety plasma samples were collected, representing 63 samples from groups at risk for acquiring HCV infection and 27 HCV RNA-positive samples. The results of Ortho HCV 3.0 ELISA, Innotest HCV Ab IV, and Monolisa HCV Ag/Ab ULTRA were fully concordant for 27 HCV RNA-positive samples. Ortho HCV 3.0 ELISA test and Innotest HCV Ab IV also gave the same results for risk groups, while three samples were found to be reactive by Monolisa HCV Ag/Ab ULTRA and were consequently found negative for HCV RNA. As two of the solely Monolisa HCV Ag/Ab ULTRA-positive samples were also hepatitis B s antigen (HBsAg)-positive, neutralization of HBsAg was performed but no arguments for the HBsAg interference were observed. In conclusion, the non-specific reactive signal was observed, in three samples using Monolisa HCV Ag/Ab ULTRA, to be negative by other serological assays, and observed to be negative in an HCV RNA assessment, a result that could not be attributed to the interference with HBsAg. In the context of diagnostic testing, no test for various HCV genotypes was observed to be superior to any other. PMID- 22076115 TI - Topical nonsteroidal anti-inflammatory drugs for management of osteoarthritis in long-term care patients. AB - Osteoarthritis is common in patients >=65 years of age. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed for osteoarthritis pain, they pose age-related cardiovascular, renal, and gastrointestinal risks. Two topical NSAIDs, diclofenac sodium 1% gel (DSG) and diclofenac sodium 1.5% in 45.5% dimethylsulfoxide solution (D-DMSO), are approved in the US for the treatment of osteoarthritis pain. Topical NSAIDs have shown efficacy and safety in knee (DSG, D-DMSO) and hand (DSG) osteoarthritis. Analyses of data from randomized controlled trials of DSG in hand and knee osteoarthritis demonstrate significant improvement of pain and function in both younger patients (<65 years) and older patients (>=65 years) and suggest good safety and tolerability. However, long-term safety data in older patients are limited. Topical NSAIDs can ease medication administration and help address barriers to pain management in older patients, such as taking multiple medications and inability to swallow, and are a valuable option for long-term care providers. PMID- 22076116 TI - Critical appraisal of pralatrexate in the management of difficult-to-treat peripheral T cell lymphoma. AB - Aggressive T cell lymphomas are a subgroup of lymphomas with a particularly poor prognosis. This is especially true for patients with recurrent or refractory disease, who typically have limited response to salvage therapy and extremely poor overall survival. For this reason, there is a strong need to develop potentially active drugs for these malignancies. Pralatrexate is a novel antifolate designed to have high affinity for reduced folate carrier type 1. Preclinical and clinical studies have demonstrated that pralatrexate has significant activity against T cell lymphomas. The dose-limiting toxicity for pralatrexate is mucositis, which can be abrogated with folic acid and vitamin B12 supplementation. Pralatrexate is the first single agent approved for the treatment of patients with relapsed or refractory peripheral T cell lymphoma. This approval was based on an overall objective response rate observed in the pivotal study. The overall response rate was 29%, with a median duration of 10.1 months. This article reviews the biochemistry, preclinical experience, metabolism, and pharmacokinetics of pralatrexate, including the clinical experience with this agent in lymphoma. Future areas of development are now focused on identifying synergistic combinations of pralatrexate with other agents and the evaluation of predictive markers for clinical benefit. PMID- 22076117 TI - Patient reported outcome data following influenza A (H1N1p) vaccination in the 2009-2010 season: web-based and telephone evaluation. AB - BACKGROUND: There has been worldwide interest in the safety of the pandemic influenza A (H1N1p) vaccines, although limited data are available from the vaccine recipients' perspective. This evaluation was designed to collect data from people who had received an influenza vaccination during the 2009-2010 season using a web-based data collection tool supplemented by telephone reporting (PROBE). METHODS: People scheduled to receive the influenza A (H1N1p) or seasonal influenza vaccines were recruited through media advertising and campaigns throughout the West of Scotland. Vaccine recipients participated in the evaluation by answering demographic and side effect questions using PROBE methodology on the day of the immunization, after 3 days, 8 days, 6 weeks, 12 weeks, and 26 weeks. RESULTS: A total of 1103 vaccine recipients including 134 young children (0-4 years) participated in the evaluation; 694 (63%) received H1N1p vaccine only, 135 (12%) seasonal vaccine only, 224 (20%) both H1N1p and seasonal vaccines, and 50 (5%) received H1N1p or seasonal vaccine with a non influenza vaccine (eg, travel or pneumococcal). Overall, 42% of recipients reported experiencing a side effect after their baseline vaccination; the most commonly reported were general and arm side effects (>20%). Injection site discomfort/pain and flu-like symptoms were reported by 57% and 24% of recipients, respectively. A significantly higher proportion of the 960 H1N1p vaccine recipients experienced a side effect (44% vs 27%, P < 0.001) or injection site discomfort/pain (61% vs 26%, P < 0.001) than those receiving seasonal influenza vaccines. Female sex and H1N1p vaccination were associated with a significantly higher risk of injection site discomfort/pain, whereas the 70+ age group was associated with a significantly lower risk. H1N1p vaccine was well tolerated by children under 5 years with side effects reported at a similar frequency to that found in the total population. CONCLUSIONS: Safety and tolerability data from influenza vaccine recipients including young children (via parents/carers) can be effectively collected using an online questionnaire with a telephone option (PROBE). The influenza A (H1N1p) vaccine was well tolerated, but was associated with more local short-term reactions than the seasonal influenza vaccine. PMID- 22076118 TI - Band structure and optical properties of hexagonal In-rich In(x)Al(1-x)N alloys. AB - Full potential linear augmented plane wave calculations have been performed to study the electronic and optical properties of In-rich In(x)Al(1-x)N alloys in the hexagonal wurtzite structure. Compositions of x = 0.9375, 0.8125 and 0.6875 are considered which follow from replacing one, three and five In atoms by Al in the 32-atom supercell. The new form of exchange correlation, i.e. Engel-Vosko's generalized gradient approximation within density functional theory, is employed. The calculations yield the band structure and total density of states as well as the imaginary part epsilon(2)(omega) of the ordinary and extraordinary dielectric function. The calculated dependence of the bandgap on the composition is in good agreement with recent experimental studies. A reversal of the valence band ordering is found between x = 0.8125 and 0.6875. The absorption features in the high-energy range of epsilon(2)(omega) are related to critical points of the band structure. The transition energies for these van Hove singularities are determined and their bowing parameters are discussed. PMID- 22076119 TI - Small interfering RNA targeting Kruppel-like factor 8 inhibits U251 glioblastoma cell growth by inducing apoptosis. AB - Small interfering RNAs (siRNAs) are small non-coding RNAs, comprising 21-23 nucleotides that regulate gene expression by transcriptionally repressing their complementary mRNAs. In particular, Kruppel-like factor 8 (KLF8) has been postulated to function as a tumor activator in various cancer cells, but not in glioblastoma. In the present study, we investigated the anti-tumorigenic effect of KLF8 siRNA in glioblastoma cells. U251 human glioblastoma cells were transfected with KLF8 siRNA and assayed for in vitro proliferation, cell cycle and cell apoptosis. The transfection of KLF8 siRNA reduced expression of KLF8 in the glioblastoma cells. KLF8 siRNA also reduced in vitro proliferation and enhanced cell apoptosis. These results indicate that KLF8 siRNA has an anti tumorigenic effect on glioblastoma cells and suggest the possible use of KLF8 siRNA for the treatment of glioblastoma. PMID- 22076120 TI - Microscopic Simulations of Charge Transport in Disordered Organic Semiconductors. AB - Charge carrier dynamics in an organic semiconductor can often be described in terms of charge hopping between localized states. The hopping rates depend on electronic coupling elements, reorganization energies, and driving forces, which vary as a function of position and orientation of the molecules. The exact evaluation of these contributions in a molecular assembly is computationally prohibitive. Various, often semiempirical, approximations are employed instead. In this work, we review some of these approaches and introduce a software toolkit which implements them. The purpose of the toolkit is to simplify the workflow for charge transport simulations, provide a uniform error control for the methods and a flexible platform for their development, and eventually allow in silico prescreening of organic semiconductors for specific applications. All implemented methods are illustrated by studying charge transport in amorphous films of tris (8-hydroxyquinoline)aluminum, a common organic semiconductor. PMID- 22076121 TI - The Nature of the Binding of Au, Ag, and Pd to Benzene, Coronene, and Graphene: From Benchmark CCSD(T) Calculations to Plane-Wave DFT Calculations. AB - The adsorption of Ag, Au, and Pd atoms on benzene, coronene, and graphene has been studied using post Hartree-Fock wave function theory (CCSD(T), MP2) and density functional theory (M06-2X, DFT-D3, PBE, vdW-DF) methods. The CCSD(T) benchmark binding energies for benzene-M (M = Pd, Au, Ag) complexes are 19.7, 4.2, and 2.3 kcal/mol, respectively. We found that the nature of binding of the three metals is different: While silver binds predominantly through dispersion interactions, the binding of palladium has a covalent character, and the binding of gold involves a subtle combination of charge transfer and dispersion interactions as well as relativistic effects. We demonstrate that the CCSD(T) benchmark binding energies for benzene-M complexes can be reproduced in plane wave density functional theory calculations by including a fraction of the exact exchange and a nonempirical van der Waals correction (EE+vdW). Applying the EE+vdW method, we obtained binding energies for the graphene-M (M = Pd, Au, Ag) complexes of 17.4, 5.6, and 4.3 kcal/mol, respectively. The trends in binding energies found for the benzene-M complexes correspond to those in coronene and graphene complexes. DFT methods that use empirical corrections to account for the effects of vdW interactions significantly overestimate binding energies in some of the studied systems. PMID- 22076122 TI - Veterans' experience in using the online Surgeon General's family health history tool. AB - AIM: To assess veterans' experience and satisfaction in using the Surgeon General's (SG) online family health history (FHH) tool, and determine the perceived facilitators and barriers to using the online SG-FHH tool. MATERIALS #ENTITYSTARTX00026; METHODS: A mixed-method using both qualitative and quantitative approaches was employed in this study. A total of 35 veterans at the VA Medical Center in San Antonio, Texas, USA were invited to enter their FHH information using the online SG-FHH tool, complete the study's satisfaction survey and participate in a short semi-structured interview. The goal of the semi structured interviews was to assess participants perceived facilitators and barriers to using the online SG-FHH tool. All participants were also provided with a printed copy of their pedigree, which was generated by the SG-FHH tool and were encouraged to share it with their relatives and providers. RESULTS: The majority of participants (91%) said that they had access to a computer with internet capability and 77% reported that they knew how to use a computer. More than two-thirds of the participants felt that items on the SG-FHH tool were easy to read and felt that FHH categories were relevant to their family's health. Approximately 94% of participants viewed the SG-FHH tool as useful, and the majority of participants (97%) indicated that they were likely to recommend the tool to others. Content analysis of the semi-structured interviews highlighted several barriers to veterans' use of the SG-FHH tool and their FHH information. These included: lack of patients' knowledge regarding their relatives' FHH, and privacy and confidentiality concerns. CONCLUSION: This study provides information on the performance and functionality of an inexpensive and widely accessible method for FHH collection. Furthermore, our findings highlight several opportunities and challenges facing the utilization of FHH information as a clinical and genomic tool at the Veterans Health Administration (VHA). The results suggest that strategies that improve veterans' knowledge regarding the importance of their FHH information and that address their concerns about privacy and confidentiality may enhance the successful implementation of FHH information into VHA clinical practice. IMPLICATIONS: identifying a locally accepted method for FHH collection and documentation which can be conducted outside of the patient visit will reduce time burdens for providers and patients and allow for a focus on other important topics during clinic visits. Improvement in familial risk screening and assessment will enable the VHA to be prepared for personalized medicine and focus their resources on promoting critically important health behaviors for populations with the highest risk of developing chronic diseases and their complications. PMID- 22076123 TI - Understanding the creative processes of phenomenological research: The life philosophy of Logstrup. AB - The creative processes of understanding patients' experiences in phenomenological research are difficult to articulate. Drawing on life philosophy as represented by the Danish philosopher K.E. Logstrup (1905-1981), this article aims to illustrate Logstrup's thinking as a way to elaborate the creation of cognition and understanding of patients' experiences. We suggest that Logstrup's thoughts on sensation can add new dimensions to an increased understanding of the creative process of phenomenological research, and that his thinking can be seen as an epistemological ground for these processes. We argue with Logstrup that sense based impressions can facilitate an flash of insight, i.e., the spontaneous, intuitive flash of an idea. Logstrup stresses that an "flash of insight" is an important source in the creation of cognition and understanding. Relating to three empirical phenomenological studies of patients' experiences, we illustrate how the notions of impression and flash of insight can add new dimensions to increased understanding of the creative processes in phenomenological research that have previously not been discussed. We illustrate that sense-based impressions can facilitate creative flash of insights that open for understanding of patients' experiences in the research process as well as in the communication of the findings. The nature of impression and flash of insight and their relevance in the creation of cognition and understanding contributes to the sparse descriptions in the methodological phenomenological research literature of the creative processes of this research. An elaboration of the creative processes in phenomenological research can help researchers to articulate these processes. Thus, Logstrup's life philosophy has proven to be valuable in adding new dimensions to phenomenological empirical research as well as embracing lived experience. PMID- 22076124 TI - ALK and NSCLC: Targeted therapy with ALK inhibitors. AB - For many years treatment for advanced or metastatic non-small cell lung cancer (NSCLC) has employed chemotherapy regimens for patient care, with limited effect. Five-year survival rates for these patients are not encouraging. However, for a subgroup of these patients, there have been radical changes over recent years. Our understanding of the basic pathology behind NSCLC at the molecular level has offered up a host of new molecularly targeted therapies, which are revolutionizing this area of cancer care. Results from recent clinical trials provide hope for NSCLC patients harboring oncogenic translocations involving the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. Just as inhibition of the breakpoint cluster region-ABL complex has changed the face of chronic myeloid leukemia diagnosis, oncogenic ALK fusions offer a step forward in the diagnosis and treatment of ALK-positive NSCLC. This article discusses the current knowledge and potential implications concerning ALK inhibitors and NSCLC. PMID- 22076125 TI - The new face of ovarian cancer modeling: better prospects for detection and treatment. AB - Ovarian cancer has a disproportionately high mortality rate because patients typically present with late-stage metastatic disease. The vast majority of these deaths are from high-grade serous carcinoma. Recent studies indicate that many of these tumors arise from the fallopian tube and subsequently metastasize to the ovary. This may explain why such tumors have not been detected at early stage as detection efforts have been focused purely on the ovary. In keeping with this leap in understanding other advances such as the development of ex-vivo models and immortalization of human fallopian tube epithelial cells, and the use of integrated genomic analyses to identify hundreds of novel candidate oncogenes and tumor suppressors potentially involved in tumorigenesis now engender hope that we can begin to truly define the differences in pathogenesis between fallopian tube and ovarian-derived tumors. In doing so, we can hopefully improve early detection, treatment, and outcome. PMID- 22076126 TI - Drugs for malaria: something old, something new, something borrowed. AB - Malaria was estimated to cause 800,000 deaths and 225 million cases worldwide in 2010. Worryingly, the first-line treatment currently relies on a single drug class called artemisinins, and there are signs that the parasite is becoming resistant to these drugs. The good news is that new technology has given us new approaches to drug discovery. New drugs generated this way are probably 10-15 years away from the clinic. Other antimalarials that may offer hope include those rehabilitated after not being used for some time, those that act as inhibitors of resistance mechanisms, those that limit infection while allowing protective immunity to develop, and those which are drugs borrowed from other disease treatments. All of these offer new hope of turning the tables on malaria. In parallel with the effort to develop vaccines that interrupt malaria transmission, drugs that target the parasite during transmission to the mosquito or during its pre-erythrocytic development in the liver, may allow us to terminate the parasite's spread. PMID- 22076128 TI - Organellar (Na+, K+)/H+ exchanger NHE7 regulates cell adhesion, invasion and anchorage-independent growth of breast cancer MDA-MB-231 cells. AB - Na+/H+ exchangers (NHEs) are a group of secondary active antiporters that regulate cellular pH, cell volume and ion homeostasis. In humans, nine isoforms (NHE1-NHE9) were identified and characterized as functional NHEs. While a growing body of evidence indicates that NHE1 generates an acidic tumor environment and thereby contributes to tumor invasion, little is known about the role of other NHE isoforms in tumor progression. NHE7 is a unique member of the NHE gene family that dynamically shuttles between the trans-Golgi network, endosomes and the plasma membrane, and regulates the luminal pH of these organelles. Here we show that NHE7-overexpression in breast cancer MDA-MB-231 cells enhances cell overlay, cell-cell adhesion, invasion, anchorage-independent tumor growth and tumor formation in vivo. In contrast, NHE1-overexpression enhances tumor invasion, but it has little effect on cell adhesion or anchorage-independent tumor growth. Pathological examinations of the tumor samples derived from NHE7-overexpressing cells showed a similar appearance to aggressive tumors. Together, these results suggest that NHE7 enhances tumor progression. This is the first report to show the involvement of an organellar NHE in oncogenic processes. PMID- 22076127 TI - Using biomarkers to improve detection of Alzheimer's disease. AB - Disease-modifying approaches for Alzheimer's disease (AD) might be most effective when initiated very early in the course, before the pathologic burden and neuronal and synaptic degeneration make it unlikely that halting disease progression would have a significant impact on patient outcomes. Biomarkers of disease may provide important avenues of research to enhance the diagnosis of individuals with early AD and could assist in the identification of those individuals at risk for developing AD. However, for such biomarkers to become clinically useful, long-term follow-up studies are necessary to evaluate the relevance of cross-sectional biomarker changes to the longitudinal course of the disease. The objective of this article is to review recent progress in AD biomarkers for the early diagnosis, classification, progression and prediction of AD and their usefulness in new treatment trials. PMID- 22076129 TI - Response of the agile antechinus to habitat edge, configuration and condition in fragmented forest. AB - Habitat fragmentation and degradation seriously threaten native animal communities. We studied the response of a small marsupial, the agile antechinus Antechinus agilis, to several environmental variables in anthropogenically fragmented Eucalyptus forest in south-east Australia. Agile antechinus were captured more in microhabitats dominated by woody debris than in other microhabitats. Relative abundances of both sexes were positively correlated with fragment core area. Male and female mass-size residuals were smaller in larger fragments. A health status indicator, haemoglobin-haematocrit residuals (HHR), did not vary as a function of any environmental variable in females, but male HHR indicated better health where sites' microhabitats were dominated by shrubs, woody debris and trees other than Eucalyptus. Females were trapped less often in edge than interior fragment habitat and their physiological stress level, indicated by the neutrophil/lymphocyte ratio in peripheral blood, was higher where fragments had a greater proportion of edge habitat. The latter trend was potentially due to lymphopoenia resulting from stress hormone-mediated leukocyte trafficking. Using multiple indicators of population condition and health status facilitates a comprehensive examination of the effects of anthropogenic disturbances, such as habitat fragmentation and degradation, on native vertebrates. Male agile antechinus' health responded negatively to habitat degradation, whilst females responded negatively to the proportion of edge habitat. The health and condition indicators used could be employed to identify conservation strategies that would make habitat fragments less stressful for this or similar native, small mammals. PMID- 22076130 TI - Patterned cell adhesion associated with tissue deformations during dorsal closure in Drosophila. AB - Cell shape changes within epithelia require the regulation of adhesive molecules that maintain tissue integrity. How remodelling of cell contacts is achieved while tissue integrity is maintained remains a fundamental question in morphogenesis. Dorsal Closure is a good system to study the dynamics of DE Cadherin during morphogenesis. It relies on concerted cell shape changes of two epithelial sheets: amnioserosa cell contraction and epidermal cell elongation. To investigate the modulation of DE-Cadherin we performed antibody uptake experiments in live embryos during Dorsal Closure. We found that some antibodies access certain epitopes of the extracellular domain of native DE-Cadherin only in the amnioserosa and epidermal cells attached to the amnioserosa, which has never been observed in fixed DE-Cadherin in Drosophila embryos. These differences correlate with the different cell behaviour of these regions and therefore we suggest that DE-Cadherin exists in different forms that confer different adhesive strengths. We propose this to be a widespread mechanism for the differential modulation of adhesion during morphogenesis. PMID- 22076131 TI - Gene clusters located on two large plasmids determine spore crystal association (SCA) in Bacillus thuringiensis subsp. finitimus strain YBT-020. AB - Crystals in Bacillus thuringiensis are usually formed in the mother cell compartment during sporulation and are separated from the spores after mother cell lysis. In a few strains, crystals are produced inside the exosporium and are associated with the spores after sporulation. This special phenotype, named 'spore crystal association' (SCA), typically occurs in B. thuringiensis subsp. finitimus. Our aim was to identify genes determining the SCA phenotype in B. thuringiensis subsp. finitimus strain YBT-020. Plasmid conjugation experiments indicated that the SCA phenotype in this strain was tightly linked with two large plasmids (pBMB26 and pBMB28). A shuttle bacterial artificial chromosome (BAC) library of strain YBT-020 was constructed. Six fragments from BAC clones were screened from this library and discovered to cover the full length of pBMB26; four others were found to cover pBMB28. Using fragment complementation testing, two fragments, each of approximately 35 kb and located on pBMB26 and pBMB28, were observed to recover the SCA phenotype in an acrystalliferous mutant, B. thuringiensis strain BMB171. Furthermore, deletion analysis indicated that the crystal protein gene cry26Aa from pBMB26, along with five genes from pBMB28, were indispensable to the SCA phenotype. Gene disruption and frame-shift mutation analyses revealed that two of the five genes from pBMB28, which showed low similarity to crystal proteins, determined the location of crystals inside the exosporium. Gene disruption revealed that the three remaining genes, similar to spore germination genes, contributed to the stability of the SCA phenotype in strain YBT-020. Our results thus identified the genes determining the SCA phenotype in B. thuringiensis subsp. finitimus. PMID- 22076132 TI - Transport activity of the sodium bicarbonate cotransporter NBCe1 is enhanced by different isoforms of carbonic anhydrase. AB - Transport metabolons have been discussed between carbonic anhydrase II (CAII) and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1), to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 uM), while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity. PMID- 22076134 TI - Prediction of disease and phenotype associations from genome-wide association studies. AB - BACKGROUND: Genome wide association studies (GWAS) have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP). The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases. METHODOLOGY/PRINCIPAL FINDINGS: Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD) and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs) were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits. CONCLUSIONS/SIGNIFICANCE: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment. PMID- 22076133 TI - Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat. AB - It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including Mck, Ttn and Mef2c. We next performed circadian time-course collections at a young age (8 weeks; pre hypertensive) and adult age (22 weeks; hypertensive) to determine if clock gene expression was disrupted in gastrocnemius, heart and liver tissues prior to or after the rats became hypertensive. We found that hypertensive/hypertrophic SHR showed a dampening of peak Bmal1 and Rev-erb expression in the liver, and the clock-controlled gene Pgc1alpha in the gastrocnemius. In addition, the core-clock gene Clock and the muscle-specific, clock-controlled gene Myod1, no longer maintained a circadian pattern of expression in gastrocnemius from the hypertensive SHR. These findings provide a framework to suggest a mechanism whereby chronic heart failure leads to skeletal muscle pathologies; prolonged dysregulation of the molecular clock in skeletal muscle results in altered Clock, Pgc1alpha and Myod1 expression which in turn leads to the mis-regulation of target genes important for mechanical and metabolic function of skeletal muscle. PMID- 22076135 TI - Erk1/2 mediates leptin receptor signaling in the ventral tegmental area. AB - Leptin acts on the ventral tegmental area (VTA) to modulate neuronal function and feeding behavior in rats and mice. To identify the intracellular effectors of the leptin receptor (Lepr), downstream signal transduction events were assessed for regulation by direct leptin infusion. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and phosphorylated extracellular signal regulated kinase-1 and -2 (pERK1/2) were increased in the VTA while phospho-AKT (pAKT) was unaffected. Pretreatment of brain slices with the mitogen-activated protein kinase kinase -1 and -2 (MEK1/2) inhibitor U0126 blocked the leptin mediated decrease in firing frequency of VTA dopamine neurons. The anorexigenic effects of VTA-administered leptin were also blocked by pretreatment with U0126, which effectively blocked phosphorylation of ERK1/2 but not STAT3. These data demonstrate that pERK1/2 may have a critical role in mediating both the electrophysiogical and behavioral effects of leptin receptor signaling in the VTA. PMID- 22076136 TI - Redistribution of CB1 cannabinoid receptors in the acute and chronic phases of pilocarpine-induced epilepsy. AB - The endocannabinoid system plays a central role in retrograde synaptic communication and may control the spread of activity in an epileptic network. Using the pilocarpine model of temporal lobe epilepsy we examined the expression pattern of the Type 1 cannabinoid receptor (CB1-R) in the hippocampi of CD1 mice at survival times of 2 hours, 1 day, 3 days and 2 months (acute, latent and chronic phases). Based on the behavioral signs of the acute seizures, animals were classified as "weakly" or "strongly" epileptic using the modified Racine scale. Mice of the weak group had mild seizures, whereas seizures in the strong group were frequent with intense motor symptoms and the majority of these animals developed sclerosis in the chronic phase. In control samples the most intense staining of CB1-R-positive fibers was found in the molecular layer of the dentate gyrus and in str. pyramidale of the cornu Ammonis. In weak animals no significant changes were seen at any survival time compared to controls. In strong animals, however, in the acute phase, a massive reduction in CB1-R-stained terminals occurred in the hippocampus. In the latent phase CB1-R immunoreactivity gradually recovered. In the chronic phase, CB1-immunostaining in sclerotic samples was stronger throughout the hippocampus. Quantitative electron microscopic analysis showed an increase in the number of CB1-R-positive terminals in the dentate gyrus. Moreover, the number of immunogold particles significantly increased in GABAergic terminals. Our results suggest a proconvulsive downregulation of CB1 receptors in the acute phase most probably due to receptor internalization, followed by compensatory upregulation and sprouting in the chronic phase of epilepsy. In conclusion, the changes in CB1 receptor expression pattern revealed in this study are associated with the severity of hippocampal injury initiated by acute seizures that ultimately leads to sclerosis in the vulnerable regions in the chronic phase. PMID- 22076137 TI - Endogenous neurotrophins and Trk signaling in diffuse large B cell lymphoma cell lines are involved in sensitivity to rituximab-induced apoptosis. AB - BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Immunochemotherapy, a combination of rituximab to standard chemotherapy, has resulted in improved survival. However a substantial proportion of patients still fail to reach sustained remission. We have previously demonstrated that autocrine brain-derived neurotrophic factor (BDNF) production plays a function in human B cell survival, at least partly via sortilin expression. As neurotrophin receptor (Trks) signaling involved activation of survival pathways that are inhibited by rituximab, we speculated that neurotrophins may provide additional support for tumour cell survival and therapeutic resistance in DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used two DLBCL cell lines, SUDHL4 and SUDHL6, known to be respectively less and more sensitive to rituximab. We found by RT-PCR, western blotting, cytometry and confocal microscopy that both cell lines expressed, in normal culture conditions, BDNF and to a lesser extent NGF, as well as truncated TrkB and p75(NTR)/sortilin death neurotrophin receptors. Furthermore, BDNF secretion was detected in cell supernatants. NGF and BDNF production and Trk receptor expression, including TrkA, are regulated by apoptotic conditions (serum deprivation or rituximab exposure). Indeed, we show for the first time that rituximab exposure of DLBCL cell lines induces NGF secretion and that differences in rituximab sensitivity are associated with differential expression patterns of neurotrophins and their receptors (TrkA). Finally, these cells are sensitive to the Trk-inhibitor, K252a, as shown by the induction of apoptosis. Furthermore, K252a exhibits additive cytotoxic effects with rituximab. CONCLUSIONS/SIGNIFICANCE: Collectively, these data strongly suggest that a neurotrophin axis, such NGF/TrkA pathway, may contribute to malignant cell survival and rituximab resistance in DLBCL. PMID- 22076138 TI - Rust secreted protein Ps87 is conserved in diverse fungal pathogens and contains a RXLR-like motif sufficient for translocation into plant cells. AB - BACKGROUND: Effector proteins of biotrophic plant pathogenic fungi and oomycetes are delivered into host cells and play important roles in both disease development and disease resistance response. How obligate fungal pathogen effectors enter host cells is poorly understood. The Ps87 gene of Puccinia striiformis encodes a protein that is conserved in diverse fungal pathogens. Ps87 homologs from a clade containing rust fungi are predicted to be secreted. The aim of this study is to test whether Ps87 may act as an effector during Puccinia striiformis infection. METHODOLOGY/PRINCIPAL FINDINGS: Yeast signal sequence trap assay showed that the rust protein Ps87 could be secreted from yeast cells, but a homolog from Magnaporthe oryzae that was not predicted to be secreted, could not. Cell re-entry and protein uptake assays showed that a region of Ps87 containing a conserved RXLR-like motif [K/R]RLTG was confirmed to be capable of delivering oomycete effector Avr1b into soybean leaf cells and carrying GFP into soybean root cells. Mutations in the Ps87 motif (KRLTG) abolished the protein translocation ability. CONCLUSIONS/SIGNIFICANCE: The results suggest that Ps87 and its secreted homologs could utilize similar protein translocation machinery as those of oomycete and other fungal pathogens. Ps87 did not show direct suppression activity on plant defense responses. These results suggest Ps87 may represent an "emerging effector" that has recently acquired the ability to enter plant cells but has not yet acquired the ability to alter host physiology. PMID- 22076139 TI - Integrated transcriptome and binding sites analysis implicates E2F in the regulation of self-renewal in human pluripotent stem cells. AB - Rapid cellular growth and multiplication, limited replicative senescence, calibrated sensitivity to apoptosis, and a capacity to differentiate into almost any cell type are major properties that underline the self-renewal capabilities of human pluripotent stem cells (hPSCs). We developed an integrated bioinformatics pipeline to understand the gene regulation and functions involved in maintaining such self-renewal properties of hPSCs compared to matched fibroblasts. An initial genome-wide screening of transcription factor activity using in silico binding-site and gene expression microarray data newly identified E2F as one of major candidate factors, revealing their significant regulation of the transcriptome. This is underscored by an elevated level of its transcription factor activity and expression in all tested pluripotent stem cell lines. Subsequent analysis of functional gene groups demonstrated the importance of the TFs to self-renewal in the pluripotency-coupled context; E2F directly targets the global signaling (e.g. self-renewal associated WNT and FGF pathways) and metabolic network (e.g. energy generation pathways, molecular transports and fatty acid metabolism) to promote its canonical functions that are driving the self-renewal of hPSCs. In addition, we proposed a core self-renewal module of regulatory interplay between E2F and, WNT and FGF pathways in these cells. Thus, we conclude that E2F plays a significant role in influencing the self-renewal capabilities of hPSCs. PMID- 22076140 TI - Assessing the role of tandem repeats in shaping the genomic architecture of great apes. AB - BACKGROUND: Ancestral reconstructions of mammalian genomes have revealed that evolutionary breakpoint regions are clustered in regions that are more prone to break and reorganize. What is still unclear to evolutionary biologists is whether these regions are physically unstable due solely to sequence composition and/or genome organization, or do they represent genomic areas where the selection against breakpoints is minimal. METHODOLOGY AND PRINCIPAL FINDINGS: Here we present a comprehensive study of the distribution of tandem repeats in great apes. We analyzed the distribution of tandem repeats in relation to the localization of evolutionary breakpoint regions in the human, chimpanzee, orangutan and macaque genomes. We observed an accumulation of tandem repeats in the genomic regions implicated in chromosomal reorganizations. In the case of the human genome our analyses revealed that evolutionary breakpoint regions contained more base pairs implicated in tandem repeats compared to synteny blocks, being the AAAT motif the most frequently involved in evolutionary regions. We found that those AAAT repeats located in evolutionary regions were preferentially associated with Alu elements. SIGNIFICANCE: Our observations provide evidence for the role of tandem repeats in shaping mammalian genome architecture. We hypothesize that an accumulation of specific tandem repeats in evolutionary regions can promote genome instability by altering the state of the chromatin conformation or by promoting the insertion of transposable elements. PMID- 22076141 TI - Alkamides activate jasmonic acid biosynthesis and signaling pathways and confer resistance to Botrytis cinerea in Arabidopsis thaliana. AB - Alkamides are fatty acid amides of wide distribution in plants, structurally related to N-acyl-L-homoserine lactones (AHLs) from Gram-negative bacteria and to N- acylethanolamines (NAEs) from plants and mammals. Global analysis of gene expression changes in Arabidopsis thaliana in response to N-isobutyl decanamide, the most highly active alkamide identified to date, revealed an overrepresentation of defense-responsive transcriptional networks. In particular, genes encoding enzymes for jasmonic acid (JA) biosynthesis increased their expression, which occurred in parallel with JA, nitric oxide (NO) and H2O2 accumulation. The activity of the alkamide to confer resistance against the necrotizing fungus Botrytis cinerea was tested by inoculating Arabidopsis detached leaves with conidiospores and evaluating disease symptoms and fungal proliferation. N-isobutyl decanamide application significantly reduced necrosis caused by the pathogen and inhibited fungal proliferation. Arabidopsis mutants jar1 and coi1 altered in JA signaling and a MAP kinase mutant (mpk6), unlike salicylic acid- (SA) related mutant eds16/sid2-1, were unable to defend from fungal attack even when N-isobutyl decanamide was supplied, indicating that alkamides could modulate some necrotrophic-associated defense responses through JA-dependent and MPK6-regulated signaling pathways. Our results suggest a role of alkamides in plant immunity induction. PMID- 22076143 TI - Perturbation of host cell cytoskeleton by cranberry proanthocyanidins and their effect on enteric infections. AB - Cranberry-derived compounds, including a fraction known as proanthocyanidins (PACs) exhibit anti-microbial, anti-infective, and anti-adhesive properties against a number of disease-causing organisms. In this study, the effect of cranberry proanthocyanidins (CPACs) on the infection of epithelial cells by two enteric bacterial pathogens, enteropathogenic Escherichia coli (EPEC) and Salmonella Typhimurium was investigated. Immunofluorescence data showed that actin pedestal formation, required for infection by enteropathogenic Escherichia coli (EPEC), was disrupted in the presence of CPACs. In addition, invasion of HeLa cells by Salmonella Typhimurium was significantly reduced, as verified by gentamicin protection assay and immunofluorescence. CPACs had no effect on bacterial growth, nor any detectable effect on the production of bacterial effector proteins of the type III secretion system. Furthermore, CPACs did not affect the viability of host cells. Interestingly, we found that CPACs had a potent and dose-dependent effect on the host cell cytoskeleton that was evident even in uninfected cells. CPACs inhibited the phagocytosis of inert particles by a macrophage cell line, providing further evidence that actin-mediated host cell functions are disrupted in the presence of cranberry CPACs. Thus, although CPAC treatment inhibited Salmonella invasion and EPEC pedestal formation, our results suggest that this is likely primarily because of the perturbation of the host cell cytoskeleton by CPACs rather than an effect on bacterial virulence itself. These findings have significant implications for the interpretation of experiments on the effects of CPACs on bacteria-host cell interactions. PMID- 22076142 TI - Maternal cigarette smoke exposure contributes to glucose intolerance and decreased brain insulin action in mice offspring independent of maternal diet. AB - BACKGROUND: Maternal smoking leads to intrauterine undernutrition and is associated with low birthweight and higher risk of offspring obesity. Intrauterine smoke exposure (SE) may alter neuroendocrine mediators regulating energy homeostasis as chemicals in cigarette smoke can reach the fetus. Maternal high-fat diet (HFD) consumption causes fetal overnutrition; however, combined effects of HFD and SE are unknown. Thus we investigated the impact of combined maternal HFD and SE on adiposity and energy metabolism in offspring. METHOD: Female Balb/c mice had SE (2 cigarettes/day, 5 days/week) or were sham exposed for 5 weeks before mating. Half of each group was fed HFD (33% fat) versus chow as control. The same treatment continued throughout gestation and lactation. Female offspring were fed chow after weaning and sacrificed at 12 weeks. RESULTS: Birthweights were similar across maternal groups. Faster growth was evident in pups from SE and/or HFD dams before weaning. At 12 weeks, offspring from HFD-fed dams were significantly heavier than those from chow-fed dams (chow-sham 17.6+/ 0.3 g; chow-SE 17.8+/-0.2 g; HFD-sham 18.7+/-0.3 g; HFD-SE 18.8+/-0.4 g, P<0.05 maternal diet effect); fat mass was significantly greater in offspring from chow+SE, HFD+SE and HFD+sham dams. Both maternal HFD and SE affected brain lactate transport. Glucose intolerance and impaired brain response to insulin were observed in SE offspring, and this was aggravated by maternal HFD consumption. CONCLUSION: While maternal HFD led to increased body weight in offspring, maternal SE independently programmed adverse health outcomes in offspring. A smoke free environment and healthy diet during pregnancy is desirable to optimize offspring health. PMID- 22076144 TI - Recognition of morphometric vertebral fractures by artificial neural networks: analysis from GISMO Lombardia Database. AB - BACKGROUND: It is known that bone mineral density (BMD) predicts the fracture's risk only partially and the severity and number of vertebral fractures are predictive of subsequent osteoporotic fractures (OF). Spinal deformity index (SDI) integrates the severity and number of morphometric vertebral fractures. Nowadays, there is interest in developing algorithms that use traditional statistics for predicting OF. Some studies suggest their poor sensitivity. Artificial Neural Networks (ANNs) could represent an alternative. So far, no study investigated ANNs ability in predicting OF and SDI. The aim of the present study is to compare ANNs and Logistic Regression (LR) in recognising, on the basis of osteoporotic risk-factors and other clinical information, patients with SDI>=1 and SDI>=5 from those with SDI = 0. METHODOLOGY: We compared ANNs prognostic performance with that of LR in identifying SDI>=1/SDI>=5 in 372 women with postmenopausal-osteoporosis (SDI>=1, n = 176; SDI = 0, n = 196; SDI>=5, n = 51), using 45 variables (44 clinical parameters plus BMD). ANNs were allowed to choose relevant input data automatically (TWIST-system-Semeion). Among 45 variables, 17 and 25 were selected by TWIST-system-Semeion, in SDI>=1 vs SDI = 0 (first) and SDI>=5 vs SDI = 0 (second) analysis. In the first analysis sensitivity of LR and ANNs was 35.8% and 72.5%, specificity 76.5% and 78.5% and accuracy 56.2% and 75.5%, respectively. In the second analysis, sensitivity of LR and ANNs was 37.3% and 74.8%, specificity 90.3% and 87.8%, and accuracy 63.8% and 81.3%, respectively. CONCLUSIONS: ANNs showed a better performance in identifying both SDI>=1 and SDI>=5, with a higher sensitivity, suggesting its promising role in the development of algorithm for predicting OF. PMID- 22076145 TI - Indirect detection of an epitope-specific response to HIV-1 gp120 immunization in human subjects. AB - A specific response of human serum neutralizing antibodies (nAb) to a conformational epitope as a result of vaccination of human subjects with the surface envelope glycoprotein (gp120) of HIV-1 has not previously been documented. Here, we used computational analysis to assess the epitope-specific responses of human subjects, which were immunized with recombinant gp120 immunogens in the VAX003 and VAX004 clinical trials. Our computational methodology--a variation of sieve analysis--compares the occurrence of specific nAb targeted conformational 3D epitopes on viruses from infected individuals who received vaccination to the occurrence of matched epitopes in the viruses infecting placebo subjects. We specifically studied seven crystallographically defined nAb targeted conformational epitopes in the V3 loop, an immunogenic region of gp120. Of the six epitopes present in the immunogens and targeted by known monoclonal neutralizing antibodies, only the one targeted by the anti-V3 nAb 2219 exhibited a significant reduction in occurrence in vaccinated subjects compared to the placebo group. This difference occurred only in the VAX003 Thailand cohort. No difference was seen between vaccinated and placebo groups for the occurrence of an epitope that was not present in the immunogen. Thus, it can be theorized that a specific 2219-like human neutralizing antibody immune response to AIDSVAX immunization occurred in the VAX003 cohort, and that this response protected subjects from a narrow subset of HIV-1 viruses circulating in Thailand in the 1990s and bearing the conformational epitope targeted by the neutralizing antibody 2219. PMID- 22076146 TI - Apoptosis-inducing factor regulates skeletal muscle progenitor cell number and muscle phenotype. AB - Apoptosis Inducing Factor (AIF) is a highly conserved, ubiquitous flavoprotein localized in the mitochondrial intermembrane space. In vivo, AIF provides protection against neuronal and cardiomyocyte apoptosis induced by oxidative stress. Conversely in vitro, AIF has been demonstrated to have a pro-apoptotic role upon induction of the mitochondrial death pathway, once AIF translocates to the nucleus where it facilitates chromatin condensation and large scale DNA fragmentation. Given that the aif hypomorphic harlequin (Hq) mutant mouse model displays severe sarcopenia, we examined skeletal muscle from the aif hypomorphic mice in more detail. Adult AIF-deficient skeletal myofibers display oxidative stress and a severe form of atrophy, associated with a loss of myonuclei and a fast to slow fiber type switch, both in "slow" muscles such as soleus, as well as in "fast" muscles such as extensor digitorum longus, most likely resulting from an increase of MEF2 activity. This fiber type switch was conserved in regenerated soleus and EDL muscles of Hq mice subjected to cardiotoxin injection. In addition, muscle regeneration in soleus and EDL muscles of Hq mice was severely delayed. Freshly cultured myofibers, soleus and EDL muscle sections from Hq mice displayed a decreased satellite cell pool, which could be rescued by pretreating aif hypomorphic mice with the manganese-salen free radical scavenger EUK-8. Satellite cell activation seems to be abnormally long in Hq primary culture compared to controls. However, AIF deficiency did not affect myoblast cell proliferation and differentiation. Thus, AIF protects skeletal muscles against oxidative stress-induced damage probably by protecting satellite cells against oxidative stress and maintaining skeletal muscle stem cell number and activation. PMID- 22076147 TI - Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys. AB - The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05). Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-beta (TGF-beta) signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans. PMID- 22076148 TI - Antidepressants stimulate hippocampal neurogenesis by inhibiting p21 expression in the subgranular zone of the hipppocampus. AB - The relationships among hippocampal neurogenesis, depression and the mechanism of action of antidepressant drugs have generated a considerable amount of controversy. The cyclin-dependent kinase (Cdk) inhibitor p21(Cip1) (p21) plays a crucial role in restraining cellular proliferation and maintaining cellular quiescence. Using in vivo and in vitro approaches the present study shows that p21 is expressed in the subgranular zone of the dentate gyrus of the hippocampus in early neuronal progenitors and in immature neurons, but not in mature neurons or astroglia. In vitro, proliferation is higher in neuronal progenitor cells derived from p21-/- mice compared to cells derived from wild-type mice. Proliferation is increased in neuronal progenitor cells after suppression of p21 using lentivirus expressing short hairpin RNA against p21. In vivo, chronic treatment with the non-selective antidepressant imipramine as well as the norepinephrine-selective reuptake inhibitor desipramine or the serotonin selective reuptake inhibitor fluoxetine all decrease p21 expression, and this was associated with increased neurogenesis. Chronic antidepressant treatment did not affect the expression of other Cdk inhibitors. Untreated p21-/- mice exhibit a higher degree of baseline neurogenesis and decreased immobility in the forced swim test. Although chronic imipramine treatment increased neurogenesis and reduced immobility in the forced swim test in wild-type mice, it reduced neurogenesis and increased immobility in p21-/- mice. These results demonstrate the unique role of p21 in the control of neurogenesis, and support the hypothesis that different classes of reuptake inhibitor-type antidepressant drugs all stimulate hippocampal neurogenesis by inhibiting p21 expression. PMID- 22076149 TI - p53 dependent centrosome clustering prevents multipolar mitosis in tetraploid cells. AB - BACKGROUND: p53 abnormality and aneuploidy often coexist in human tumors, and tetraploidy is considered as an intermediate between normal diploidy and aneuploidy. The purpose of this study was to investigate whether and how p53 influences the transformation from tetraploidy to aneuploidy. PRINCIPAL FINDINGS: Live cell imaging was performed to determine the fates and mitotic behaviors of several human and mouse tetraploid cells with different p53 status, and centrosome and spindle immunostaining was used to investigate centrosome behaviors. We found that p53 dominant-negative mutation, point mutation, or knockout led to a 2~ 33-fold increase of multipolar mitosis in N/TERT1, 3T3 and mouse embryonic fibroblasts (MEFs), while mitotic entry and cell death were not significantly affected. In p53-/- tetraploid MEFs, the ability of centrosome clustering was compromised, while centrosome inactivation was not affected. Suppression of RhoA/ROCK activity by specific inhibitors in p53-/- tetraploid MEFs enhanced centrosome clustering, decreased multipolar mitosis from 38% to 20% and 16% for RhoA and ROCK, respectively, while expression of constitutively active RhoA in p53+/+ tetraploid 3T3 cells increased the frequency of multipolar mitosis from 15% to 35%. CONCLUSIONS: p53 could not prevent tetraploid cells entering mitosis or induce tetraploid cell death. However, p53 abnormality impaired centrosome clustering and lead to multipolar mitosis in tetraploid cells by modulating the RhoA/ROCK signaling pathway. PMID- 22076150 TI - Genome-scale consequences of cofactor balancing in engineered pentose utilization pathways in Saccharomyces cerevisiae. AB - Biofuels derived from lignocellulosic biomass offer promising alternative renewable energy sources for transportation fuels. Significant effort has been made to engineer Saccharomyces cerevisiae to efficiently ferment pentose sugars such as D-xylose and L-arabinose into biofuels such as ethanol through heterologous expression of the fungal D-xylose and L-arabinose pathways. However, one of the major bottlenecks in these fungal pathways is that the cofactors are not balanced, which contributes to inefficient utilization of pentose sugars. We utilized a genome-scale model of S. cerevisiae to predict the maximal achievable growth rate for cofactor balanced and imbalanced D-xylose and L-arabinose utilization pathways. Dynamic flux balance analysis (DFBA) was used to simulate batch fermentation of glucose, D-xylose, and L-arabinose. The dynamic models and experimental results are in good agreement for the wild type and for the engineered D-xylose utilization pathway. Cofactor balancing the engineered D xylose and L-arabinose utilization pathways simulated an increase in ethanol batch production of 24.7% while simultaneously reducing the predicted substrate utilization time by 70%. Furthermore, the effects of cofactor balancing the engineered pentose utilization pathways were evaluated throughout the genome scale metabolic network. This work not only provides new insights to the global network effects of cofactor balancing but also provides useful guidelines for engineering a recombinant yeast strain with cofactor balanced engineered pathways that efficiently co-utilizes pentose and hexose sugars for biofuels production. Experimental switching of cofactor usage in enzymes has been demonstrated, but is a time-consuming effort. Therefore, systems biology models that can predict the likely outcome of such strain engineering efforts are highly useful for motivating which efforts are likely to be worth the significant time investment. PMID- 22076151 TI - An in vivo polymicrobial biofilm wound infection model to study interspecies interactions. AB - Chronic wound infections are typically polymicrobial; however, most in vivo studies have focused on monospecies infections. This project was designed to develop an in vivo, polymicrobial, biofilm-related, infected wound model in order to study multispecies biofilm dynamics and in relation to wound chronicity. Multispecies biofilms consisting of both Gram negative and Gram positive strains, as well as aerobes and anaerobes, were grown in vitro and then transplanted onto the wounds of mice. These in vitro-to-in vivo multi-species biofilm transplants generated polymicrobial wound infections, which remained heterogeneous with four bacterial species throughout the experiment. We observed that wounded mice given multispecies biofilm infections displayed a wound healing impairment over mice infected with a single-species of bacteria. In addition, the bacteria in the polymicrobial wound infections displayed increased antimicrobial tolerance in comparison to those in single species infections. These data suggest that synergistic interactions between different bacterial species in wounds may contribute to healing delays and/or antibiotic tolerance. PMID- 22076153 TI - Derivation, characterization, and stable transfection of induced pluripotent stem cells from Fischer344 rats. AB - The rat represents an important animal model that, in many respects, is superior to the mouse for dissecting behavioral, cardiovascular and other physiological pathologies relevant to humans. Derivation of induced pluripotent stem cells from rats (riPS) opens the opportunity for gene targeting in specific rat strains, as well as for the development of new protocols for the treatment of different degenerative diseases. Here, we report an improved lentivirus-based hit-and-run riPS derivation protocol that makes use of small inhibitors of MEK and GSK3. We demonstrate that the excision of proviruses does not affect either the karyotype or the differentiation ability of these cells. We show that the established riPS cells are readily amenable to genetic manipulations such as stable electroporation. Finally, we propose a genetic tool for an improvement of riPS cell quality in culture. These data may prompt iPS cell-based gene targeting in rat as well as the development of iPS cell-based therapies using disease models established in this species. PMID- 22076152 TI - Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. AB - The actin-bundling protein, fascin, is a member of the cytoskeletal protein family that has restricted expression in specialized normal cells. However, many studies have reported the induction of this protein in various transformed cells including breast cancer cells. While the role of fascin in the regulation of breast cancer cell migration has been previously shown, the underlying molecular mechanism remained poorly defined. We have used variety of immunological and functional assays to study whether fascin regulates breast cancer metastasis associated molecules. In this report we found a direct relationship between fascin expression in breast cancer patients and; metastasis and shorter disease free survival. Most importantly, in vitro interference with fascin expression by loss or gain of function demonstrates a central role for this protein in regulating the cell morphology, migration and invasion potential. Our results show that fascin regulation of invasion is mediated via modulating several metastasis-associated genes. We show for the first time that fascin down regulates the expression and nuclear translocation of a key metastasis suppressor protein known as breast cancer metastasis suppressor-1 (BRMS1). In addition, fascin up-regulates NF-kappa B activity, which is essential for metastasis. Importantly, fascin up-regulates other proteins that are known to be critical for the execution of metastasis such as urokinase-type plasminogen activator (uPA) and the matrix metalloproteases (MMP)-2 and MMP-9. This study demonstrates that fascin expression in breast cancer cells establishes a gene expression profile consistent with metastatic tumors and offers a potential therapeutic intervention in metastatic breast cancer treatment through fascin targeting. PMID- 22076154 TI - Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment. AB - BACKGROUND: The contribution of aberrant DNA methylation in silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations are reversible, it became of interest to determine the effects of the 5-aza-2'-deoxycytidine (DAC) demethylation therapy in breast cancer at different molecular levels. METHODS AND FINDINGS: Here we investigate a synoptic model to predict complete DAC treatment effects at the level of genes, microRNAs and proteins for several human breast cancer lines. The present study assessed an effective treatment dosage based on the cell viability, cytotoxicity, apoptosis and methylation assays for the investigated cell lines. A highly aggressive and a non-aggressive cell line were investigated using omics approaches such as MALDI-TOF MS, mRNA- and microRNA expression arrays, 2-D gel electrophoresis and LC-MS-MS. Complete molecular profiles including the biological interaction and possible early and late systematic stable or transient effects of the methylation inhibition were determined. Beside the activation of several epigenetically suppressed TSGs, we also showed significant dysregulation of some important oncogenes, oncomiRs and oncosuppressors miRNAs as well as drug tolerance genes/miRNAs/proteins. CONCLUSIONS: In the present study, the results denote some new molecular DAC targets and pathways based on the chemical modification of DNA methylation in breast cancer. The outlined approach might prove to be useful as an epigenetic treatment model also for other human solid tumors in the management of cancer patients. PMID- 22076155 TI - LINE-1 methylation levels in leukocyte DNA and risk of renal cell cancer. AB - PURPOSE: Leukocyte global DNA methylation levels are currently being considered as biomarkers of cancer susceptibility and have been associated with risk of several cancers. In this study, we aimed to examine the association between long interspersed nuclear elements (LINE-1) methylation levels, as a biomarker of global DNA methylation in blood cell DNA, and renal cell cancer risk. EXPERIMENTAL DESIGN: LINE-1 methylation of bisulfite-converted genomic DNA isolated from leukocytes was quantified by pyrosequencing measured in triplicate, and averaged across 4 CpG sites. A total of 328 RCC cases and 654 controls frequency-matched(2?1) on age(+/-5years), sex and study center, from a large case control study conducted in Central and Eastern Europe were evaluated. RESULTS: LINE-1 methylation levels were significantly higher in RCC cases with a median of 81.97% (interquartile range[IQR]: 80.84-83.47) compared to 81.67% (IQR: 80.35 83.03) among controls (p = 0.003, Wilcoxon). Compared to the lowest LINE-1 methylation quartile(Q1), the adjusted ORs for increasing methylation quartiles were as follows: OR(Q2) = 1.84(1.20-2.81), OR(Q3) = 1.72(1.11-2.65) and OR(Q4) = 2.06(1.34-3.17), with a p-trend = 0.004. The association was stronger among current smokers (p-trend<0.001) than former or never smokers (p-interaction = 0.03). To eliminate the possibility of selection bias among controls, the relationship between LINE-1 methylation and smoking was evaluated and confirmed in a case-only analysis, as well. CONCLUSIONS: Higher levels of LINE-1 methylation appear to be positively associated with RCC risk, particularly among current smokers. Further investigations using both post- and pre-diagnostic genomic DNA is warranted to confirm findings and will be necessary to determine whether the observed differences occur prior to, or as a result of carcinogenesis. PMID- 22076156 TI - The primate community of Cachoeira (Brazilian Amazonia): a model to decipher ecological partitioning among extinct species. AB - Dental microwear analysis is conducted on a community of platyrrhine primates from South America. This analysis focuses on the primate community of Cachoeira Porteira (Para, Brazil), in which seven sympatric species occur: Alouatta seniculus, Ateles paniscus, Cebus apella, Chiropotes satanas, Pithecia Pithecia, Saguinus midas, and Saimiri sciureus. Shearing quotients are also calculated for each taxon of this primate community. Dental microwear results indicate significant differences between taxa, but are somewhat insufficient when it comes to discriminating between ecologically similar taxa. The primates of Cachoeira Porteira all incorporate a certain amount of fruit in their diet, entailing a definite amount of inter-specific competition as they must share food resources. Alouatta is the most folivorous taxon of this community, which is corroborated by dental microwear analysis. Ateles, although of a similar size to Alouatta, limits inter-specific competition by incorporating more fruit in its diet. Cebus has a very diverse omnivorous diet, which is highlighted in this study, as it compares to both fruit and leaf eating taxa. In some cases, microwear results need to be supplemented by other methods. For example, dental microwear seems insufficient to distinguish between Pithecia and Chiropotes, which eat foods with similar physical properties. However, other methods (i.e. shearing quotients and body mass) provide enough complimentary information to be able to highlight differences between the two taxa. On the other hand, dental microwear can highlight differences between primates which have similar diets, such as Saimiri and Saguinus. In this case, differences could be due to other exogenous factors. PMID- 22076157 TI - Cerebroventricular microinjection (CVMI) into adult zebrafish brain is an efficient misexpression method for forebrain ventricular cells. AB - The teleost fish Danio rerio (zebrafish) has a remarkable ability to generate newborn neurons in its brain at adult stages of its lifespan-a process called adult neurogenesis. This ability relies on proliferating ventricular progenitors and is in striking contrast to mammalian brains that have rather restricted capacity for adult neurogenesis. Therefore, investigating the zebrafish brain can help not only to elucidate the molecular mechanisms of widespread adult neurogenesis in a vertebrate species, but also to design therapies in humans with what we learn from this teleost. Yet, understanding the cellular behavior and molecular programs underlying different biological processes in the adult zebrafish brain requires techniques that allow manipulation of gene function. As a complementary method to the currently used misexpression techniques in zebrafish, such as transgenic approaches or electroporation-based delivery of DNA, we devised a cerebroventricular microinjection (CVMI)-assisted knockdown protocol that relies on vivo morpholino oligonucleotides, which do not require electroporation for cellular uptake. This rapid method allows uniform and efficient knockdown of genes in the ventricular cells of the zebrafish brain, which contain the neurogenic progenitors. We also provide data on the use of CVMI for growth factor administration to the brain--in our case FGF8, which modulates the proliferation rate of the ventricular cells. In this paper, we describe the CVMI method and discuss its potential uses in zebrafish. PMID- 22076158 TI - Characterization of the sortase repertoire in Bacillus anthracis. AB - LPXTG proteins, present in most if not all Gram-positive bacteria, are known to be anchored by sortases to the bacterial peptidoglycan. More than one sortase gene is often encoded in a bacterial species, and each sortase is supposed to specifically anchor given LPXTG proteins, depending of the sequence of the C terminal cell wall sorting signal (cwss), bearing an LPXTG motif or another recognition sequence. B. anthracis possesses three sortase genes. B. anthracis sortase deleted mutant strains are not affected in their virulence. To determine the sortase repertoires, we developed a genetic screen using the property of the gamma phage to lyse bacteria only when its receptor, GamR, an LPXTG protein, is exposed at the surface. We identified 10 proteins that contain a cell wall sorting signal and are covalently anchored to the peptidoglycan. Some chimeric proteins yielded phage lysis in all sortase mutant strains, suggesting that cwss proteins remained surface accessible in absence of their anchoring sortase, probably as a consequence of membrane localization of yet uncleaved precursor proteins. For definite assignment of the sortase repertoires, we consequently relied on a complementary test, using a biochemical approach, namely immunoblot experiments. The sortase anchoring nine of these proteins has thus been determined. The absence of virulence defect of the sortase mutants could be a consequence of the membrane localization of the cwss proteins. PMID- 22076159 TI - Intravenous neuromyelitis optica autoantibody in mice targets aquaporin-4 in peripheral organs and area postrema. AB - The pathogenesis of neuromyelitis optica (NMO) involves binding of IgG autoantibodies (NMO-IgG) to aquaporin-4 (AQP4) on astrocytes in the central nervous system (CNS). We studied the in vivo processing in mice of a recombinant monoclonal human NMO-IgG that binds strongly to mouse AQP4. Following intravenous administration, serum [NMO-IgG] decreased with t(1/2) ~18 hours in wildtype mice and ~41 hours in AQP4 knockout mice. NMO-IgG was localized to AQP4-expressing cell membranes in kidney (collecting duct), skeletal muscle, trachea (epithelial cells) and stomach (parietal cells). NMO-IgG was seen on astrocytes in the area postrema in brain, but not elsewhere in brain, spinal cord, optic nerve or retina. Intravenously administered NMO-IgG was also seen in brain following mechanical disruption of the blood-brain barrier. Selective cellular localization was not found for control (non-NMO) IgG, or for NMO-IgG in AQP4 knockout mice. NMO-IgG injected directly into brain parenchyma diffused over an area of ~5 mm2 over 24 hours and targeted astrocyte foot-processes. Our data establish NMO-IgG pharmacokinetics and tissue distribution in mice. The rapid access of serum NMO IgG to AQP4 in peripheral organs but not the CNS indicates that restricted antibody access cannot account for the absence of NMO pathology in peripheral organs. PMID- 22076160 TI - Regional grey and white matter changes in heavy male smokers. AB - Cigarette smoking is highly prevalent in the general population but the effects of chronic smoking on brain structures are still unclear. Previous studies have found mixed results regarding regional grey matter abnormalities in smokers. To characterize both grey and white matter changes in heavy male smokers, we investigated 16 heavy smokers and 16 matched healthy controls, using both univariate voxel-based morphometry (VBM) and multivariate pattern classification analysis. Compared with controls, heavy smokers exhibited smaller grey matter volume in cerebellum, as well as larger white matter volume in putamen, anterior and middle cingulate cortex. Further, the spatial patterns of grey matter or white matter both discriminated smokers from controls in these regions as well as in other brain regions. Our findings demonstrated volume abnormalities not only in the grey matter but also in the white matter in heavy male smokers. The multivariate analysis suggests that chronic smoking may be associated with volume alternations in broader brain regions than those identified in VBM analysis. These results may better our understanding of the neurobiological consequence of smoking and inform smoking treatment. PMID- 22076161 TI - In vitro acute exposure to DEHP affects oocyte meiotic maturation, energy and oxidative stress parameters in a large animal model. AB - Phthalates are ubiquitous environmental contaminants because of their use in plastics and other common consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is the most abundant phthalate and it impairs fertility by acting as an endocrine disruptor. The aim of the present study was to analyze the effects of in vitro acute exposure to DEHP on oocyte maturation, energy and oxidative status in the horse, a large animal model. Cumulus cell (CC) apoptosis and oxidative status were also investigated. Cumulus-oocyte complexes from the ovaries of slaughtered mares were cultured in vitro in presence of 0.12, 12 and 1200 uM DEHP. After in vitro maturation (IVM), CCs were removed and evaluated for apoptosis (cytological assessment and TUNEL) and intracellular reactive oxygen species (ROS) levels. Oocytes were evaluated for nuclear chromatin configuration. Matured (Metaphase II stage; MII) oocytes were further evaluated for cytoplasmic energy and oxidative parameters. DEHP significantly inhibited oocyte maturation when added at low doses (0.12 uM; P<0.05). This effect was related to increased CC apoptosis (P<0.001) and reduced ROS levels (P<0.0001). At higher doses (12 and 1200 uM), DEHP induced apoptosis (P<0.0001) and ROS increase (P<0.0001) in CCs without affecting oocyte maturation. In DEHP-exposed MII oocytes, mitochondrial distribution patterns, apparent energy status (MitoTracker fluorescence intensity), intracellular ROS localization and levels, mt/ROS colocalization and total SOD activity did not vary, whereas increased ATP content (P<0.05), possibly of glycolytic origin, was found. Co-treatment with N-Acetyl-Cysteine reversed apoptosis and efficiently scavenged excessive ROS in DEHP-treated CCs without enhancing oocyte maturation. In conclusion, acute in vitro exposure to DEHP inhibits equine oocyte maturation without altering ooplasmic energy and oxidative stress parameters in matured oocytes which retain the potential to be fertilized and develop into embryos even though further studies are necessary to confirm this possibility. PMID- 22076162 TI - Circulation of different lineages of dengue virus type 2 in Central America, their evolutionary time-scale and selection pressure analysis. AB - Dengue is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Each serotype is genetically distant from the others, and each has been subdivided into different genotypes based on phylogenetic analysis. The study of dengue evolution in endemic regions is important since the diagnosis is often made by nucleic acid amplification tests, which depends upon recognition of the viral genome target, and natural occurring mutations can affect the performance of these assays. Here we report for the first time a detailed study of the phylogenetic relationships of DENV-2 from Central America, and report the first fully sequenced DENV-2 strain from Guatemala. Our analysis of the envelope (E) protein and of the open reading frame of strains from Central American countries, between 1999 and 2009, revealed that at least two lineages of the American/Asian genotype of DENV-2 have recently circulated in that region. In occasions the co circulation of these lineages may have occurred and that has been suggested to play a role in the observed increased severity of clinical cases. Our time-scale analysis indicated that the most recent common ancestor for Central American DENV 2 of the American/Asian genotype existed about 19 years ago. Finally, we report positive selection in DENV-2 from Central America in codons of the genes encoding for C, E, NS2A, NS3, and NS5 proteins. Some of these identified codons are novel findings, described for the first time for any of the DENV-2 genotypes. PMID- 22076163 TI - Role of leptin and its receptors in the pathogenesis of thyroid cancer. AB - Leptin is a multifunctional adipose-derived cytokines that play a critical role in bodyweight homeostasis and energy balance. Recently, leptin and leptin receptor dysreulation have been reported in variety of malignant cells including thyroid. Leptin modulates growth and proliferation of cancer cells via activation of various growth and survival signaling pathways including JAK/STAT, PI3 kinase/AKT and/or Map kinases. In this review, current understanding of leptin's role in the pathogenesis of thyroid cancer has been described. PMID- 22076164 TI - The oncogenic gene fusion TMPRSS2: ERG is not a diagnostic or prognostic marker for ovarian cancer. AB - TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening. PMID- 22076165 TI - Glioblastoma with PNET-like components has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and likely a better prognosis than primary glioblastoma. AB - Glioblastoma with primitive neuroectodermal tumor-like components (GBM-PNET), a rare variant of glioblastoma, poses both diagnostic and therapeutic challenges. Ten patients with GBM-PNET were investigated with a median age of 51.5 years and the male to female ratio of 4:1. The majority of patients (7 out of 10) showed ring-enhancing lesions on magnetic resonance imaging (MRI), which is classic for GBMs. Restricted diffusion was noted in 7 cases where diffusion weighted imaging (DWI) was performed, which correlates with the presence of PNET-like components. CD56 and vimentin immunostaining made the diagnosis of GBM-PNET much easier. Vimentin strongly and diffusely highlighted the astrocytic components and was negative in PNET-like components, while CD56 was strongly and diffusely positive in both astrocytic and PNET-like components. Seven out of 9 cases were positive for p53 in both astrocytic and PNET-like components. Two out of 8 cases harbored isocitrate dehydrogenase 1 (IDH1) R132H mutation, while IDH2 R172 mutations were not identified. Three out of 10 patients had a median survival time of 17 months while the two patients, whose tumor carried IDH1 mutation, were still alive after 15 and 31 months of follow-up. Compared to primary GBMs, GBM-PNETs might have a better prognosis. Further large scale studies are necessary to confirm this observation. PMID- 22076166 TI - Increased expression of zinc finger protein 267 in non-alcoholic fatty liver disease. AB - Hepatocellular lipid accumulation is a hallmark of non-alcoholicfatty liver disease (NAFLD), which encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and ultimately cirrhosis. Zinc finger protein 267 (ZNF267) belongs to the family of Kruppel-like transcription factors, which regulate diverse biological processes that include development, proliferation, and differentiation. We have previously demonstrated that ZNF267 expression is up-regulated in liver cirrhosis and is further increased in hepatocellular carcinoma (HCC). Here, we analyzed the expression of ZNF267 in tissue specimens of NAFLD patients and found a significant up-regulation compared to normal liver tissue. Noteworthy, ZNF267 mRNA was already significantly increased in steatotic liver tissue without inflammation. In line with this, incubation of primary human hepatocytes with palmitic acid induced a dose dependent lipid accumulation and corresponding dose-dependent ZNF267 induction in vitro. Furthermore, hepatocellular lipid accumulation induced formation of reactive oxygen species (ROS), and also chemically induced ROS formation increased ZNF267 mRNA expression. In summary with previous findings, which revealed ZNF267 as pro-fibrogenic and pro-cancerogenic factor in chronic liver disease, the present study further suggests ZNF267 as promising therapeutic target particularly for NAFLD patients. In addition, it further indicates that hepatic steatosis per se has pathophysiological relevance and should not be considered as benign. PMID- 22076167 TI - Claudins 10 and 18 are predominantly expressed in lung adenocarcinomas and in tumors of nonsmokers. AB - AIMS: We investigated the expression of claudins 18 and 10 in a large set of primary lung carcinomas. METHODS AND RESULTS: Immunohistochemical expression of claudin 18 was seen in 12.7 % and claudin 10 in 12.5 % of lung carcinomas. Their expression significantly associated with each other (p<0.001). The expression of claudin 18 and 10 was most prominent in lung adenocarcinomas which displayed positivity in 21.2% and 23.4 % of cases. Female patients had more often claudin 18 and 10 positive tumors, also separately in adenocarcinomas. Interestingly, claudin 10 (p=0.036) and claudin 18 (p=0.001) were more common in tumours of nonsmokers. In adenocarcinomas claudin 18 predicted a better survival (p=0.032). In Cox multivariate analysis, claudin 18 had an independent prognostic value (p=0.027). CONCLUSION: The results show that both claudins are most commonly expressed in lung adenocarcinomas and they are more occasionally detected in other histological tumour types. Curiously, female patients and non-smokers express these claudins more commonly suggesting that they may play a part in the carcinogenesis of tobacco unrelated carcinoma. Claudin 18 associated with a better survival in lung adenocarcinoma and had an independent prognostic value and may thus be used in the evaluation of patient prognosis. PMID- 22076168 TI - Co-expression of metalloproteinases 11 and 12 in cervical scrapes cells from cervical precursor lesions. AB - The metalloproteinases (MMP) 11 and 12 have been shown to be expressed in cervical cancer (CC). In order to extend our previous results, these MMPs were evaluated in cervical precursor lesions. One hundred seventeen cervical scrapes: thirty-six normal, thirty-six low grade squamous lesions (LSIL), thirty-six high grade (HSIL), nine CC; and, also ninety-nine paraffin-embedded cervical lesions: fifteen normal cervices, thirty eight LSIL, sixteen HSIL, and five CC were collected. The samples were analyzed for relative expression by real time RT-PCR or immunohistochemistry assay. We were able to identify a relative increased expression of MMP11 in 75% and 78% from LSIL and HSIL samples, respectively. While MMP12 expression was 64% and 75% in LSIL and HSIL, respectively. Positive samples for MMP11 expression were also positive for MMP12 expression and also increased according to illness progression. In the tissues, MMP11 or MMP12 expression was observed in the cytoplasm of the neoplastic cells, while in the normal epithelium was absent. The reaction was always stronger for MMP12 than MMP11. MMP11 expression was present in 77% and 66% of LSIL and HSIL, while MMP12 expression was 73% and 68%. There was a relationship between MMP11 or MMP12 expression and HPV infection. Our data are showing a relationship between diagnostic of precursor lesions and the MMP11 and 12 expressions, suggesting that their expression could be an early event in the neoplastic lesions of the cervix and could have clinical significance. PMID- 22076169 TI - Achilles tendinosis: a morphometrical study in a rat model. AB - This study addresses the morphopathogenesis of Achilles tendinosis, using a rat model and presenting quantitative analysis of time-dependent histological changes. Thirty Wistar rats were used, randomly split in experimental and control groups. Animals of the experimental group were submitted to a treadmill running scheme. Five animals of each group were euthanized at four, eight and sixteen weeks. Achilles tendons were collected and processed routinely for histopath sections. Slides were stained by Hematoxylin-Eosin, Picrosirius Red, Alcian Blue, AgNOR, TUNEL and evaluated morphometrically. Cellular density decreased slightly along the time and was higher in the experimental group than in controls at fourth, eighth and sixteenth weeks. Fiber microtearing, percentual of reticular fibers and glycosaminoglycans content increased along the time and were higher in experimental group than in controls at all-time intervals. AgNOR labeling here interpreted as a marker of transcription activity was higher in the experimental groups than in controls at all-time intervals. Apoptotic cells were more frequent and diffusely distributed in tendinosis samples than in control groups. These results suggest that as mechanical overload is becoming chronic, cellular turnover and matrix deposition increases leading to tendinosis. The combination of staining techniques and morphometry used here to describe the evolution of lesions occurring in a rat model system has proved to be suited for the study of induced Achilles tendinosis. PMID- 22076171 TI - Small oncocytic papillary renal cell carcinoma in diabetic glomerulosclerosis. AB - Histologic and immunohistochemical features of oncocytic papillary renal cell carcinoma (RCC) have not been fully elucidated. The author herein report a case of oncocytic papillary RCC (OPRCC). A 71-year-old man with diabetes mellitus and diabetic nephropathy was found to have a small right renal tumor by CT. He had been treated with hemodialysis for chronic renal failure for 10 years. A nephrectomy was performed. Grossly, a small (1.5cm) encapsulated yellow tumor was found in the kidney. Histologically, the tumor was completely encapsulated, and consisted entirely of atypical oncocytes arranged in a diffuse papillary structure with fibrovascular cores. The oncocytes showed grade 3 atypia and pseudostratification. A few mitotic figures were seen, and psammoma bodies, foamy macrophages, and hemosiderin were scattered. Histochemically, the tumor cells were positive for colloidal iron, and negative for mucins (Alcian blue/PAS). Immunohistochemical results of the tumor were as follows: alpha-methylacyl coenzyme A rasemase (AMACR) +++, vimentin +++, cytokeratin (CK) 18 +++, CD10 +++, S-100 protein +, MUC1 ++, MUC2 ++, MUC5AC ++, MUC6 ++, panCK Cam5.2 +, CK7 +, CK8 +, CK14 +, CK19 +, CK20 +, p53 +, HepPar1 +, CD68 +, platelet-derived growth factor-alpha (PDGFRA) +, PanCK AE1/3 -, PanCK WSS -, PanCK MNF115 -, CK 35BE12 -, CK5/6 -, EMA -, desmin -, smooth muscle antigen -, alpha-fetoprotein -, CEA -, estrogen receptor -, progesterone receptor -, HER2 -, p63 -, and KIT -. Ki67 labeling was 6%. These results suggest that OPRCC can express colloidal iron, low molecular weight CKs, S100 protein, MUC1, MUC2, MUC5AC, MUC6, p53, PDGFRA, and HepPar1. PMID- 22076172 TI - Extranodal NK/T-cell lymphoma, nasal type extensively involving the bone marrow. AB - Extranodal NK/T-cell lymphoma, nasal type, is an aggressive EBV-associated lymphoma that mainly involves the nasal cavity but has also been reported to involve other extranodal sites without nasal involvement. In contrast to aggressive NK cell leukemia (a marrow-based aggressive leukemia of NK-cell origin); extensive bone marrow and blood involvement is extremely uncommon by nasal type NK/T lymphoma. We report a patient with extranodal NK/T-cell lymphoma, nasal type that developed extensive bone marrow involvement during the course of her disease with some overlapping features with aggressive NK-cell leukemia. PMID- 22076170 TI - Modulation of AP-endonuclease1 levels associated with hepatic cirrhosis in rat model treated with human umbilical cord blood mononuclear stem cells. AB - Oxidative stress in liver cells may contribute to the etiology of hepatic diseases, as in liver cirrhosis. AP-Endonuclease1 (APE1/Ref-1) is essential for cell protection toward oxidative stress by acting as a transcriptional regulator of pro-survival genes and as a redox sensitive protein. The aim of this study was to critically analyze the various parameters governing the success of human umbilical cord blood mononuclear stem cell-based (MNCs) therapy without the use of an immunosuppressant and to investigate for the first time the expression of APE1 during thioacetamide (TAA)-induced cirrhosis and MNCs therapy in a rat model. Umbilical cord blood samples from full-term deliveries were collected. Lethal fulminant hepatic cirrhosis in rats was induced by intraperitoneal injection of thio-acetamide. MNCs were then intrahepatically transplanted. We measured APE1 expression at mRNA and protein levels, mRNA expression of TGF-beta, alpha-SMA, STAP, CTGF, MMP-9 and TIMP-1 in a follow up study. Histopathological and immunohistochemical analyses were performed 10 weeks after intrahepatic injection of the cells. Transdifferentiated cells could be efficiently stained with antihuman hepatocytes. Interestingly, human hepatocyte-specific markers, human albumin, cytokeratin-18 and cytokeratin-19 mRNAs were detected in rat liver after 10 days of MNCs infusion. MNC transplanted by intrahepatic route, could engraft recipient liver, differentiated into functional hepatocytes, and rescued liver failure. Moreover up regulation of APE1 expression confirmed by marked immunohistochemical staining may be involved in MNCs-induced hepatocytes regeneration suggesting that maintaining high level of APE1 has protective effect as pro-survival signal. PMID- 22076173 TI - KIT and PDGFRA in esophageal pure small cell carcinoma. AB - The author herein reports a very rare case of pure small cell carcinoma of the esophagus with an emphasis on KIT and PDGFRA. A 72-year-old man was admitted to our hospital because of dysphagia, and endoscopy showed a tumor in the esophagus. A biopsy of the esophageal tumor showed a small cell carcinoma consisting of malignant small cells with very hyperchromatic nuclei and inconspicuous nucleoli and without any differentiations. An immuno-histochemical study revealed positive reaction for cytokeratin (Dako, Glostrup, Denmark), KIT, PDGFRA, synapto-physin, p53 protein, and CD56, and negative reaction for chromogranin, CD45, CD20, CD3, and CD30. The Ki-67 labeling was 95%. A molecular genetic analysis showed no mutations of KIT and PDGFRA genes. The patient underwent radiation (50 Gray) and chemotherapy (cisplatin, 5 courses), but he developed liver and bone metastases and died of systemic carcinomatosis five months after the initial presentation. PMID- 22076174 TI - Translocation (5; 11) in a conjunctival MALT lymphoma. AB - Lymphoma is the most frequent malignant tumor of the ocular adnexa with the most common histologic type being extranodal marginal zone B-cell lymphoma (EMZL) of mucosa-associated lymphoid tissue (MALT lymphoma). Here we report a case of a 28 year-old male who presented with a left conjunctival mass of one year duration. A diagnosis of primary MALT lymphoma of the conjunctiva was made based on morphologic and immunopheno-typic studies. Chromosome analysis revealed a male karyotype with a translocation t (5;11) (q33;p11.2) as the primary chromosomal abnormality, which, to the best of our knowledge, is the first reported translocation in MALT lym-phomas and ocular MALT lymphomas as well. PMID- 22076175 TI - Monstrous epithelial cell clusters in the seminal vesicle. AB - A 60-year-old man presented with dysuria and elevated PSA (6.95 ng/ml). Needle biopsies of the prostate revealed well differentiated adenocarcinoma of Gleason's score 6. Prostatectomy and bilateral seminal vesiculotomy were performed. The material was totally cut into 16 preparations. The prostate showed well differentiated adenocarcinoma. The left seminal vesicle showed intraluminal monstrous large epithelial cells with acidophilic cytoplasm and hyperchromatic nuclei, simulating carcinoma cells. Lipochrome pigment was present in the monstrous cells, and some monstrous cells showed large bizarre nuclei. Such monstrous cells were also present in the mucosal seminal vesicle epithelium, and gradual merge between the intraluminal and mucosal monstorous epithelium. Immunohistochemically, the monstrous epithelial cells showed the following reactions: pancytokeratin (AE1/3, CAM5.2) +, cytokeratin (CK) 5/6 +, CK34betaE12 , CK7 +, CK8 -, CK14 -, CK18 +, CK19+, CK20 -, Ki-67 0%, p53 -, P63 -, NSE -, CEA -, EMA -, CA19-9 -, ER -, PgR -, HER2 -, HepPar1 -, CD34 -, CD10 +, PSA -, AMACR , Desmin -, ASMA -, CD68 -, S100 -, CD45 -, synaptopysin -, TTF-1 -, CDX-2 -, MUC1 -, MUC2 -, MUC5AC - MUC6 +, CD56 -, PAS -, dPAS -, and alcian blue +. The immunoprofile of normal seminal vesicle epithelium was as follows: pancytokeratin (AE1/3, CAM5.2) +++, cy-tokeratin (CK) 5/6 +++, CK34betaE12 -, CK7 +++, CK8 +, CK14 -, CK18 +++, CK19, +++, CK20 -, KI-67 1%, p53 -, P63 +++, NSE -, CEA - EMA , CA19-9 -, ER -, PgR -, HER2 +, HepPar1 -, CD34 -, CD10 +, PSA -, AMACR -, Desmin -, ASMA -, CD68 -, S100 - , CD45 -, synaptopysin -, TTF-1 -, CDX-2 -, MUC1 -, MUC2 -, MUC5AC -, MUC6 +++, CD56 -, PAS -, dPAS -, and alcian blue +. That is, the immunophenotype was very similar but much weaker in monstrous cells than in normal seminal vesicle epithelium. These findings suggest that the monstrous seminal vesicle epithelial cells are degenerative changes. The monstrous epithelial cells should not be mistaken for carcinoma. PMID- 22076176 TI - Mark A. Smith, 1965-2010: consummate student of pathogenesis. PMID- 22076179 TI - Microsatellite instability is associated with the clinicopathologic features of gastric cancer in sporadic gastric cancer patients. AB - PURPOSE: Replication error is an important mechanism in carcinogenesis. The microsatellite instability (MSI-H) of colorectal cancers is associated with the development of multiple cancers. The influence of MSI-H on the development of multiple gastric cancers in sporadic gastric cancer patients has not been defined. This study was performed to reveal the association between the clinicopathologic features and MSI in sporadic gastric cancers. MATERIALS AND METHODS: Between July 2004 and March 2009, the clinicopathologic characteristics, including MSI status, were evaluated in 128 consecutive patients with sporadic gastric cancers. None of the patients had hereditary non-polyposis colorectal cancer of familial gastric cancer. The markers that were recommended by the NCI to determine the MSI status for colorectal cancers were used. RESULTS: MSI-H cancers were found in 10.9% of the patients (14/128). Synchronous gastric cancers were shown in 4 patients (3.1%). Synchronous cancers were found in 2 of 14 patients with MSI-H gastric cancer (14.3%) and 2 of 114 patients with MSS gastric cancer (1.8%; P=0.059, Fisher's exact test). Among the patients with synchronous cancer 50% (2/4) had MSI-H cancer, but 9.7% of the patients (12/124) without synchronous cancer had MSI-H cancer. MSI-H (RR, 24.7; 95% CI, 1.5~398.9; P=0.024) was related with to synchronous gastric cancer, but age, gender, family history, histologic type, location, gross morphology, size, and stage were not related to synchronous gastric cancer. CONCLUSIONS: MSI is associated with the intestinal type gastric cancer and the presence of multiple gastric cancers in patients with sporadic gastric cancer. Special attention to the presence of synchronous and the development of metachronous multiple cancer in patients with MSI-H gastric cancer is needed. PMID- 22076177 TI - Rationale for Targeting CD6 as a Treatment for Autoimmune Diseases. AB - CD6 is a 105-130 kDa surface glycoprotein expressed on the majority of T cells and a subset of B cells. The human cd6 gene maps to chromosome 11, and the expression of its protein product is tightly regulated. CD6 mediates cellular adhesion migration across the endothelial and epithelial cells. In addition, it participates in the antigen presentation by B cells and the subsequent proliferation of T cells. CD6 may bind in trans to surface glycoproteins (such as ALCAM and 3A11), or to microbial lipopolysaccharides, and may bind in cis to endogenous ligands (such as CD3 and CD5), and thereby deliver a costimulatory signal. Transinteractions are reinforced during autoimmune diseases (e.g., rheumatoid arthritis (RA), Sjogren's syndrome, and multiple sclerosis) and some cancers. Based on experimental data and on clinical results in RA and psoriasis, we believe that the recent humanized anti-CD6-specific mAb T1h may act as a regulator of the immunological response in addition to its function as an anti-T- and -B cell agent. PMID- 22076178 TI - B-cell pathology in juvenile idiopathic arthritis. AB - Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic arthritis in childhood and adolescents and encompasses a heterogeneous group of different diseases. Due to the promising results of B-cell depleting therapies in rheumatoid arthritis the role of B-cells in autoimmune diseases has to be discussed in a new context. Additionally, experiments in mouse models have shed new light on the antibody-independent role of B-cells in the development of autoimmune diseases. In this review we will discuss the importance of B-cells in the pathogenesis of JIA appraising the question for an immunological basis of B cell targeted therapy in JIA. PMID- 22076180 TI - In vitro adenosine triphosphate based chemotherapy response assay in gastric cancer. AB - PURPOSE: The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer. MATERIALS AND METHODS: A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index. RESULTS: The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin. CONCLUSIONS: ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen. PMID- 22076181 TI - Frequency and predictive factors of lymph node metastasis in mucosal cancer. AB - PURPOSE: The incidence of lymph node metastasis has been reported to range from 2.6 to 4.8% in early stage gastric cancer with mucosal invasion (T1a cancer). Lymph node metastasis in early stage gastric cancer is known as an important predictive factor. We analyzed the prediction factors of lymph node metastasis in T1a cancer. MATERIALS AND METHODS: A total of 9,912 patients underwent radical gastrectomy due to gastric cancer from October 1994 to July 2006 in the Department Of Surgery at Samsung Medical Center. We did a retrospective analysis of 2,524 patients of these patients, ones for whom the cancer was confined within the mucosa. RESULTS: Among the 2,524 patients, 57 (2.2%) were diagnosed with lymph node metastasis, and of these, cancer staging was as follows: 41 were N1, 8 were N2, and 8 were N3a. Univariate analysis of clinicopathological factors showed that the following factors were significant predictors of metastasis: tumor size larger than 4 cm, the presence of middle and lower stomach cancer, poorly differentiated adenocarcinoma and signet-ring cell carcinoma, diffuse type cancer (by the Lauren classification), and lymphatic invasion. Multivariate analysis showed that lymphatic invasion and tumor larger than 4 cm were significant factors with P<0.001 and P=0.024, respectively. CONCLUSIONS: The frequency of lymph node metastasis is extremely low in early gastric cancer with mucosal invasion. However, when lymphatic invasion is present or the tumor is larger than 4 cm, there is a greater likelihood of lymph node metastasis. In such cases, surgical treatments should be done to prevent disease recurrence. PMID- 22076182 TI - Phenotypic Differences of Gastric Cancer according to the Helicobacter pylori Infection in Korean Patients. AB - PURPOSE: Infection with Helicobacter pylori is an important risk factor for gastric cancer in humans. We compared the clinicopathologic features of gastric cancer patients based on H. pylori infection. MATERIALS AND METHODS: We prospectively studied 155 patients who had gastric cancer and underwent gastrectomies in 1 hospital in Korea. We examined H. pylori infections using the rapid urease test (RUT) with gastrectomy specimens and collected clinical and pathologic data. RESULTS: The number of H. pylori infections based on the RUT was 137 (88%). The H. pylori-negative group was significantly associated with AGC and tumor histology. H. pylori infection was significantly correlated with type I/IIa in EGC and type III/IV/V in AGC. AGC was significantly correlated with larger tumor size, lymphatic invasion, perineural invasion, and H. pylori infection based on univariate and multivariate analyses. CONCLUSIONS: We report the prevalence of H. pylori based on the RUT in gastric cancer patients. H. pylori infection influences the tumor histology, progression, and growth type of gastric cancer. PMID- 22076183 TI - The diagnostic accuracy of endoscopic biopsy for gastric dysplasia. AB - PURPOSE: There is controversy over the treatment for low grade dysplasia, while resection is recommended for high grade dysplasia. But the concordance of the grade of dysplasia between pre- and post-resection is low because of sampling errors with endoscopic biopsy. We attempted to establish a clearer direction for the treatment of dysplasia by clarifying the discrepancy between the pre- and post-resection diagnoses. MATERIALS AND METHODS: We performed a retrospective review of 126 patients who had undergone resection with the diagnosis of dysplasia on biopsy at Bundang CHA Hospital from 1999 to 2009. RESULTS: Seventy patients were diagnosed with low grade dysplasia and 56 patients were diagnosed with high grade dysplasia. Among the 33 patients who received gastrectomy with lymph node dissection, 30 patients were revealed to have invasive cancers and 4 patients showed lymph node metastasis. Discordance between the diagnoses from biopsy and resection occurred in 55 patients (44%). There was no correlation on the comparative analysis between the size, location or gross type of lesion and the grade of dysplasia. CONCLUSIONS: The rate of discordance between the diagnoses of endoscopic biopsy and the post resection pathologic report was as high as 44%. Endoscopic mucosal resection was not sufficient for some patients who were diagnosed with dysplasia on biopsy due to the presence of lymph node metastasis. It is necessary to be prudent when determining the follow-up and treatment based solely on the result of the biopsy. PMID- 22076184 TI - Is Surgical Treatment Necessary after Non-curative Endoscopic Resection for Early Gastric Cancer? AB - PURPOSE: Additional surgery is commonly recommended in gastric cancer patients who have a high risk of lymph node metastasis or a positive resection margin after endoscopic resection. We conducted this study to determine factors related to residual cancer and to determine the appropriate treatment strategy. MATERIALS AND METHODS: A total of 28 patients who underwent curative gastrectomy due to non curative endoscopic resection for early gastric cancer between January 2006 and June 2009 were enrolled in this study. Their clinicopathological findings were reviewed retrospectively and analyzed for residual cancer. RESULTS: Of the 28 patients, surgical specimens showed residual cancers in eight cases (28.6%) and lymph node metastasis in one case (3.8%). Based on results of the endoscopic resection method, the rate of residual cancer was significantly different between the en-bloc resection group (17.4%) and the piecemeal resection group (80.0%). The rate of residual cancer was significantly different between the diffuse type group (100%) and the intestinal type group (20%). The rate of residual cancer in the positive lateral margin group (25.0%) was significantly lower than that in the positive vertical margin group (33.3%) or in the positive lateral and vertical margin group (66.7%). CONCLUSIONS: We recommended that patients who were lateral and vertical margin positive, had a diffuse type, or underwent piecemeal endoscopic resection, should be treated by surgery. Minimal invasive procedures can be considered for patients who were lateral margin positive and intestinal type through histopathological examination after en-bloc endoscopic resection. PMID- 22076185 TI - Image-based Approach for Surgical Resection of Gastric Submucosal Tumors. AB - PURPOSE: This study was done to evaluate the usefulness of preoperative computed tomography (CT) and intraoperative laparoscopic ultrasound to facilitate treatment of gastric submucosal tumors. MATERIALS AND METHODS: The feasibility of laparoscopic wedge resection as determined by CT findings of tumor size, location, and growth pattern was correlated with surgical findings in 89 consecutive operations. The role of laparoscopic ultrasound for tumor localization was analyzed. RESULTS: Twenty-three patients were considered unsuitable for laparoscopic wedge resection because of large tumor size (N=13) or involvement of the gastroesophageal junction (N=9) or pyloric channel (N=1). Laparoscopic wedge resection was not attempted in 11 of these patients because of large tumor size. Laparoscopic wedge resection was successfully performed in 65 of 66 (98.5%) patients considered suitable for this procedure. Incorrect interpretation of preoperative CT resulted in a change of surgery type in seven patients (7.9%): incorrect CT diagnosis on gastroesophageal junction involvement (N=6) and on growth pattern (N=1). In 18 patients without an exophytic growth pattern, laparoscopic ultrasound was necessary and successfully localized all lesions. CONCLUSIONS: Preoperative CT and laparoscopic ultrasound are useful for surgical planning and tumor localization in laparoscopic wedge resection. PMID- 22076186 TI - Prognostic significance of preoperative blood transfusion in stomach cancer. AB - PURPOSE: We did a retrospective study to understand the prognostic effects of preoperative blood transfusions in stomach cancer surgery. MATERIALS AND METHODS: Data for 1,360 patients who underwent gastrectomy for stomach cancer between 2001 and 2009 were retrospectively reviewed. We analyzed factors that affect preoperative transfusion and clinicopathologic features. We also analyzed 5-year and overall survival rates of the transfusion and non transfusion subgroups. RESULTS: Sixty patients (4.4%) required blood transfusion within the preoperative period. The transfused group included patients who took aspirin or clopidogrel (P<0.001), with more advanced T stages (P<0.001), with more advanced nodal metastasis (P=0.00), and with more advanced stages (P=0.00) than the non transfusion group. On multivariate analysis, preoperative transfusion was a statistically significant negative influence on 5-year survival and overall survival rates (58.2% vs 79.9% (P=0.00), 58.2% vs 76.8% (P=0.00)). Applying Cox regression analyses, blood transfusion did appear to have an effect on prognosis and on 5-year and overall survival rates. CONCLUSIONS: We found a direct negative relation between preoperative transfusion and long term prognosis in patients receiving gastric cancer surgery. PMID- 22076187 TI - The feasibility of short term prophylactic antibiotics in gastric cancer surgery. AB - PURPOSE: Most surgeons administer prophylactic antibiotics for 3 to 5 days postoperatively. However, the Center for Disease Control (CDC) guideline recommends antibiotic therapy for 24 hours or less in clean/uncontaminated surgery. Thus, we prospectively studied the use of short term prophylactic antibiotic therapy after gastric cancer surgery. MATERIALS AND METHODS: A total of 103 patients who underwent gastric cancer surgery between October 2007 and June 2008 were prospectively enrolled in a short term prophylactic antibiotics program. One gram of cefoxitin was administered 30 minutes before the incision, and one additional gram was administered intraoperatively for cases with an operation time over 3 hours. Postoperatively, one gram was administered 3 times, every 8 hours. Patients were checked routinely for fever. All cases received open surgery, and the surgical wounds were dressed and checked for Surgical Site Infection (SSI) daily. RESULTS: Of the 103 patients, 15 were dropped based on exclusion criteria (severe organ dysfunction, combined resection of the colon, etc). The remaining 88 patients were included in the short-term program of prophylactic antibiotic use. Of these patients, SSIs were detected in 8 (9.1%) and fever after 2 postoperative days was detected in 11 (12.5%). The incidence of SSIs increased with patient age, and postoperative fever correlated with operation time. CONCLUSIONS: Short term prophylactic antibiotic usage is feasible in patients who undergo gastric cancer surgery, and where there are no grave comorbidities or combined resection. PMID- 22076188 TI - Clinicopathological Features of Upper Third Gastric Cancer during a 21-Year Period (Single Center Analysis). AB - PURPOSE: The aim of this study was to determine proportions of upper third gastric cancer (UTG) among all gastric cancers and analyze clinicopathological features of the disease. MATERIALS AND METHODS: The medical records of 12,300 patients who underwent gastric surgery between 1986 and 2006 at Seoul National University Hospital (SNUH) were retrospectively reviewed. Clinicopathological features of 1,260 patients with UTG and 9,929 patients with middle or lower third gastric cancer (MLG) were compared, and annual proportions of UTG were evaluated. RESULTS: The proportion of patients with UTG rapidly increased from 2.6% in 1986 to 12.5% in 1992. However, linear regression analysis showed that the rate of increase was reduced (0.21%/year) after 1992 (12.5% to 14.2% from 1992 to 2006). Compared with the MLG group, the UTG group had a lower proportion of (22.3% vs. 39.7%, P<0.001) and a greater proportion of stage III/IV disease (39.4% vs. 31.7%, P<0.001). The UTG group also had larger tumors than the MLG group in stages I/II and III (3.5 cm/5.3 cm/6.5 cm vs. 3.2 cm/5.0 cm/5.8 cm, P=0.020/0.028 /<0.001), a higher proportion of undifferentiated cancer (63.1% vs. 53.7%, P<0.001), and less intestinal Lauren's type (38.8% vs. 47.4%, P<0.001). The 5 year survival rate of the UTG group was significantly lower than that of the MLG group in stages I/II and III (85.6%/63.1%/34.2% vs. 91.6%/ 69.2%/44.7%, P<0.001/0.028/0.006). CONCLUSIONS: The proportion of UTGs has increased over the last two decades at SNUH, but the rate of increase has been greatly reduced since 1992. The UTG group showed a poorer prognosis compared with the MLG group in stages I/II and III. PMID- 22076189 TI - Clinicopathological characteristics and prognosis of remnant gastric cancer. AB - PURPOSE: The long-term survival rate of gastric cancer patients after surgery has recently increased as a result of making an early diagnosis of gastric cancer. Therefore, the incidence of remnant gastric cancer is increasing. This study was performed to evaluate the clinicopathological characteristics and prognosis of patients with remnant gastric cancer. MATERIALS AND METHODS: From January 2005 to December 2009, twenty-nine patients with remnant gastric cancer and who underwent surgery at Pusan National University Hospital were enrolled in this study. We retrospectively reviewed and analyzed their medical records. We also divided them into two groups: the remnant gastric cancer (RGC)-B group (first operation for benign disease) and the RGC-M group (first operation for malignant disease). RESULTS: The RGC-B group included ten patients and the RGC-M group included nineteen patients. The mean interval between the first and second operations was 17 years. The curative resection rate was 93.1% (27/29). The postoperative complication rate was 20.7% (6/29) and there was no perioperative mortality. Ten (37%) of twenty-seven patients experienced recurrence after curative resection and eight patients (27.6%) expired due to aggravation of remnant stomach cancer. An advanced TNM stage and non-curative resection were the negative prognostic factors for survival for patients with remnant stomach cancer (P=0.0453 and P<0.001). The RGC-M group showed a shorter interval (P<0.001) and the RGC-B group had more advanced TNM stage (P=0.003). CONCLUSIONS: Long-term follow-up should be considered not only for patients who undergo an operation for malignant disease, but also for the patients who underwent an operation for benign disease. When remnant gastric cancer is diagnosed, curative resection is essential to improve the survival. PMID- 22076190 TI - Which Is the Optimal Extent of Resection in Middle Third Gastric Cancer between Total Gastrectomy and Subtotal Gastrectomy? AB - PURPOSE: In resectable gastric cancer, choice regarding the extent of resection depends on tumor size, location, and distance from resection margin. However, there remains controversy for choice of resection for tumors in the middle third of the stomach. This study investigated patients who underwent gastrectomy in order to analyze the differences between total gastrectomy (TG) and subtotal gastrectomy (STG). MATERIALS AND METHODS: From 2000 to 2006, 125 patients with a tumor in the middle third of the stomach underwent radical gastric resection at EUMC. We retrospectively conducted comparative analysis for the differences in clinicopathological characteristics and prognosis between TG and STG. RESULTS: The average tumor size was 6.7 cm for TG, and 4.1 cm for STG. The number of metastatic lymph nodes were 13.3 for TG, and 3.7 for STG. Patients with more advanced cancer were more likely to receive TG. The 5-year survival rate for TG was lower (38.1%) than STG (69.0%). However, if tumor stages were stratified, there was no significant difference in the survival rate. Histologically, for the undifferentiated type of cancer (Stage 1, 2), the 5-year survival rate of STG was higher (88.1%) than TG (75.0%). CONCLUSIONS: Comparing patients with tumors in the middle third of the stomach who underwent TG and STG, there was no statistically significant difference in the 5-year survival rate. If stages were stratified, the clinicopathological characteristic becomes a key factor in deciding the prognosis, rather than the choice of resection. Thus if the radical resection margin can be obtained for a tumor in the middle third of the stomach, STG is considered instead of TG. PMID- 22076191 TI - Feasibility of gastric cancer surgery at low volume hospitals. AB - PURPOSE: Most gastric cancer patients undergo operations at large tertiary hospitals in Korea. However, some patients are treated at low volume hospitals. We investigated patient outcomes after gastric surgery at a secondary hospital and compared with outcomes of large volume centers. MATERIALS AND METHODS: We included 184 patients who underwent gastric surgery for gastric cancer at our hospital from January 2003 to December 2008. We conducted a retrospective study and evaluated the clinicopathological characteristics, clinical outcomes and survival rate of patients. RESULTS: Mean age was 61.7 years old. Male to female ratio was 2.2 : 1. Proportion of early gastric cancer was 38.6% and that of advanced gastric cancer was 61.4%. The 5 year overall survival rate of 184 patients was 66.3%. The overall survival rate was significantly lower for people over 62 years old. The morbidity rate and mortality at our hospital were 10.3% and 0.5%, respectively. CONCLUSIONS: The overall survival rate, morbidity and mortality were similar to those of the previous reports from Korea. Treatment of gastric cancer at a secondary hospital is feasible and safe. Standardization of operations and management of gastric cancer patients of the Korean Gastric Cancer Association is the most important factor to achieve these outcomes. PMID- 22076192 TI - The Early Experience of Laparoscopy-assisted Gastrectomy for Gastric Cancer at a Low-volume Center. AB - PURPOSE: Laparoscopy-assisted gastrectomy (LAG) has become a technically feasible and safe procedure for early gastric cancer treatment. LAG is being increasingly performed in many centers; however, there have been few reports regarding LAG at low-volume centers. The aim of this study was to report our early experience with LAG in patients with gastric cancer at a low-volume center. MATERIALS AND METHODS: The clinicopathologic data and surgical outcomes of 39 patients who underwent LAG for gastric cancer between April 2007 and March 2010 were retrospectively reviewed. RESULTS: The mean age was 68.3 years. Thirty-one patients had medical co-morbidities. The mean patient ASA score was 2.0. Among the 39 patients, 4 patients underwent total gastrectomies and 35 patients underwent distal gastrectomies. The mean blood loss was 145.4 ml and the mean operative time was 259.4 minutes. The mean time-to-first flatus, first oral intake, and the postoperative hospital stay was 2.8, 3.1, and 9.3 days, respectively. The 30-day mortality rate was 0%. Postoperative complications developed in 9 patients, as follows: anastomotic leakage, 1; wound infection, 1; gastric stasis, 2; postoperative ileus, 1; pneumonia, 1; cerebral infarction, 1; chronic renal failure, 1; and postoperative psychosis, 1. CONCLUSIONS: LAG is technically feasible and can be performed safely at a low-volume center, but an experienced surgical team and careful patient selection are necessary. Furthermore, for early mastery of the learning curve for LAG, surgeons need education and training in addition to an accumulation of cases. PMID- 22076193 TI - Comparison of Learning Curves and Clinical Outcomes between Laparoscopy-assisted Distal Gastrectomy and Open Distal Gastrectomy. AB - PURPOSE: Most stomach surgeons have been educated sufficiently in conventional open distal gastrectomy (ODG) but insufficiently in laparoscopy-assisted distal gastrectomy (LADG). We compared learning curves and clinical outcomes between ODG and LADG by a single surgeon who had sufficient education of ODG and insufficient education of LADG. MATERIALS AND METHODS: ODG (90 patients, January through September, 2004) and LADG groups (90 patients, June 2006 to June 2007) were compared. The learning curve was assessed with the mean number of retrieved lymph nodes, operation time, and postoperative morbidity/mortality. RESULTS: Mean operation time was 168.3 minutes for ODG and 183.6 minutes for LADG. The mean number of retrieved lymph nodes was 37.9. Up to about the 20th to 25th cases, the slope decrease in the learning curve for LADG was more apparent than for ODG, although they both reached plateaus after the 50th cases. The mean number of retrieved lymph nodes reached the overall mean after the 30th and 40th cases for ODG and LADG, respectively. For ODG, complications were evenly distributed throughout the subgroups, whereas for LADG, complications occurred in 10 (33.3%) of the first 30 cases. CONCLUSIONS: Compared with conventional ODG, LADG is feasible, in particular for a surgeon who has had much experience with conventional ODG, although LADG required more operative time, slightly more time to get adequately retrieved lymph nodes and more complications. However, there were more minor problems in the first 30 LADG than ODG cases. The unfavorable results for LADG can be overcome easily through an adequate training program for LADG. PMID- 22076194 TI - Gastric lipomatosis. AB - Gastric lipomatosis is an extremely rare condition. We present a case of a 69 year-old woman admitted with epigastric soreness. Computerized tomography (CT) revealed extrinsically compressing, fat-containing mass lesions on the entire gastric wall of the antrum and body except for the lesser curvature. A subtotal gastrectomy was performed. Pathology findings confirmed a gastric lipomatosis with multiple gastric ulcerations and extensive disruptions of the muscular layers. This case and reports of other gastric lipomatosis cases indicate that CT should be used to characterize large submucosal masses because CT can show the specific nature and extent of the disease. We believe that surgical treatment is the most appropriate treatment for symptomatic gastric lipomatosis that shows extensive gastric involvement, or when there are multiple gastric lipomas. PMID- 22076195 TI - Recent evolution of surgical treatment for gastric cancer in Korea. AB - Gastric cancer is the most common malignancy and the incidence is steadily increasing in Korea. The principal treatment modality for gastric cancer is surgical extirpation of tumor along with draining lymph nodes. Gastrectomy with D2 lymph node dissection has been well established as a standard of surgery and improved the survival of gastric cancer patients. Recently, technological advances are drastically reshaping the landscape of surgical treatment of gastric cancer. One of the most notable trends is that minimal access surgery becomes dominating the treatment of early stage diseases. For advanced diseases, the standard access surgery is considered a reference treatment. Although there is a pilot study underway to evaluate the feasibility of the application of minimal access surgery to advanced gastric cancer (AGC), the evidence for oncological safety is not yet provided sufficiently. Based on the recent randomized controlled trials, the extent of surgery for AGC has re-defined as para-aortic lymph node dissection dose not add any survival benefit while increasing surgery related morbidities. In addition, it is now accepted as a standard operation omitting unnecessary procedures such as splenectomy and/or distal pancreatectomy for prophylactic lymph node dissection. Conceptual and technical innovation has contributed to decreasing morbidity and mortality without impairing oncological safety. All these recent advances in the field of gastric cancer surgery would be concluded in maximizing therapeutic index for gastric cancer while improving quality of life. PMID- 22076196 TI - Prevalence, pathophysiology, screening and management of osteoporosis in gastric cancer patients. AB - Osteoporosis in gastric cancer patients is often overlooked or even neglected despite its high prevalence in these patients. Considering that old age, malnutrition, chronic disease, chemotherapy, decreased body mass index and gastrectomy are independent risk factors for osteoporosis, it is reasonable that the prevalence of osteoporosis in gastric cancer patients would be high. Many surviving patients suffer from back pain and pathological fractures, which are related to osteoporosis. Fractures have obvious associated morbidities, negative impact on quality of life, and impose both direct and indirect costs. In the era of a >55.6% 5-year survival rate of gastric cancer and increased longevity in gastric cancer patients, it is very important to eliminate common sequelae such as osteoporosis. Fortunately, the diagnosis of osteoporosis is well established and many therapeutic agents have been shown to be effective and safe not only in postmenopausal females but also in elderly males. Recently, effective treatments of gastric cancer patients with osteoporosis using bisphosphonates, which are commonly used in postmenopausal woman, were reported. PMID- 22076197 TI - Eupatilin Inhibits Gastric Cancer Cell Growth by Blocking STAT3-Mediated VEGF Expression. AB - PURPOSE: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived from Artemisia asiatica. It has been reported to possess anti-tumor activity in some types of cancer including gastric cancer. Eupatilin may modulate the angiogenesis pathway which is part of anti-inflammatory effect demonstrated in gastric mucosal injury models. Here we investigated the anti-tumor effects of eupatilin on gastric cancer cells and elucidated the potential underlying mechanism whereby eupatilin suppresses angiogenesis and tumor growth. MATERIALS AND METHODS: The impact of eupatilin on the expression of angiogenesis pathway proteins was assessed using western blots in MKN45 cells. Using a chromatin immunoprecipitation assay, we tested whether eupatilin affects the recruitment of signal transducer and activator of transcription 3 (STAT3), aryl hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor-1alpha (HIF 1alpha) to the human VEGF promoter. To investigate the effect of eupatilin on vasculogenesis, tube formation assays were conducted using human umbilical vein endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in mouse xenografts was assessed. RESULTS: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF-1alpha to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much foreshortened and severely broken tubes with eupatilin treatment. In addition, eupatilin effectively reduced tumor growth in a mouse xenograft model. CONCLUSIONS: Our results indicate that eupatilin inhibits angiogenesis in gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of gastric cancer. PMID- 22076198 TI - Clinicopathological characteristics of alpha-fetoprotein-producing gastric cancer. AB - PURPOSE: alpha-fetoprotein (AFP)-producing gastric cancer is a rare tumor with high rates of liver metastasis and a poor prognosis. Many studies have been performed but there have been no comprehensive investigations of the clinicopathological and prognosis. MATERIALS AND METHODS: Six hundred ninety four patients with gastric cancer who underwent a curative gastric resection in Hanyang University Hospital from February 2001 to December 2008 were evaluated retrospectively after excluding active or chronic hepatits, liver cirrhosis and preoperative distant metastasis. Among them, thirty five patients had an elevated serum level of AFP (>7 ng/ml) preoperatively. The clinicopathological features of AFP-producing gastric cancer were analyzed. RESULTS: There was poorer differentiation, a higher incidence of lymph node metastasis, more marked lymphatic and vascular invasion in the AFP-positive group than in the AFP negative group. The 5-year survival rate of the AFP-positive group was significantly poorer than that in the AFP-negative group (66% vs. 80%, P=0.002). A significantly higher incidence of liver metastasis was observed in the AFP positive group than in the AFP-negative group (14.3% vs. 3.6%, P=0.002) with a shorter median time period from the operation to the metachronous liver metastasis (3.7 months vs. 14.1 months, P=0.043). Multivariate survival analysis revealed the depth of invasion, degree of lymph node metastasis and AFP positivity to be the independent prognostic factors. CONCLUSIONS: AFP-producing gastric cancers have an aggressive behavior with a high metastatic potential to the liver. In addition, their clinicopathological features are quite different from the more common AFP-negative gastric cancer. PMID- 22076199 TI - Metachronous ovarian metastases following resection of the primary gastric cancer. AB - PURPOSE: We performed this study to evaluate the clinical presentation as well as the proper surgical intervention for ovarian metastasis from gastric cancers and these tumors were identified during postoperative follow-up. This will help establish the optimal strategy for improving the survival of patients with this entity. MATERIALS AND METHODS: 22 patients (3.2%) with ovarian metastasis were noted when performing a retrospective chart review of (693) females patients who had undergone a resection for gastric cancer between 1981 and 2008. The covariates used for the survival analysis were the patient age at the time of ovarian relapse, the size of the tumor, the initial TNM stage of the gastric cancer, the interval to metastasis and the presence of gross residual disease after treatment for Krukenberg tumor. The cumulative survival curves for the patient groups were calculated with the Kaplan-Meier method and they were compared by means of the Log-Rank test. RESULTS: The average age of the patients was 48.6 years (range: 24 to 78 years) and the average survival time of the 22 patients was 18.8 months (the estimated 3-year survival rate was 15.8%) with a range of 2 to 59 months after the diagnosis of Krukenberg tumor. The survival rate for patients without gross residual disease was longer than that of the patients with gross residual disease (P=0.0003). In contrast, patient age, the size of ovarian tumor, the initial stage of gastric adenocarcinoma, the interval to metastasis and adjuvant chemotherapy were not prognostic indicators for survival after the development of ovarian metastasis. CONCLUSIONS: Early diagnosis and complete resection are the only possible hope to improve survival. As the 3-year survival rate after resection of Krukenberg tumor is 15.8%, it seems worthwhile to consider performing tumorectomy as the second cytoreduction. PMID- 22076200 TI - Bone metastasis in gastric cancer patients. AB - PURPOSE: Bone metastasis from stomach cancer occurs only rarely and it is known to have a very poor prognosis. This study examined the clinical characteristics and prognosis of patients who were diagnosed with stomach cancer and bone metastasis. MATERIALS AND METHODS: The subjects were 19 patients who were diagnosed with stomach cancer at Hanyang University Medical Center from June 1992 to August 2010 and they also had bone metastasis. The survival rate according to many clinicopathologic factors was retrospectively analyzed. RESULTS: 11 patients out of 18 patients (61%) who received an operation were in stage IV and the most common bone metastasis location was the spine. Bone scintigraphy was mostly used for diagnosing bone metastasis and PET-CT and magnetic resonance imaging were used singly or together. The serum alkaline phosphatase at the time of diagnosis had increased in 12 cases and there were clinical symptoms (bone pain) in 16 cases. Treatment was given to 14 cases and it was mostly radiotherapy. There were 2 cases of discovering bone metastasis at the time of diagnosing stomach cancer. The interval after operation to the time of diagnosing bone metastasis for the 18 cases that received a stomach cancer operation was on average 14.9+/-17.3 months and the period until death after the diagnosis of bone metastasis was on average 3.8+/-2.6 months. As a result of univariate survival rate analysis, the group that was treated for bone metastasis had a significantly better survival period when the bone metastasis was singular rather than multiple, as compared to the non-treatment group, yet both factors were not independent prognosis factors on multivariate survival analysis. CONCLUSIONS: An examination to confirm the status of bone metastasis when conducting a radio-tracer test after the initial diagnosis and also after an operation is needed for stomach cancer patients, and bone scintigraphy is the most helpfully modality. Making the diagnosis at the early stage and suitable treatments are expected to enhance the survival rate and improve the quality of life even for the patients with bone metastasis. PMID- 22076201 TI - Clinicopathologic Characteristics of Gastric Cancer Patients according to the Timing of the Recurrence after Curative Surgery. AB - PURPOSE: There are few studies that have focused on the predictors of recurrence after gastrectomy for gastric carcinoma. This study analyzed the patients who died of recurrent gastric carcinoma and we attempted to clarify the clinicopathologic factors that are associated with the timing of recurrence. MATERIALS AND METHODS: From June 1992 to March 2009, 1,795 patients underwent curative gastric resection at the Department of Surgery, Hanyang University College of Medicine. Among them, 428 patients died and 311 of these patients who died of recurrent gastric carcinoma were enrolled in this study. The clinicopathologic findings were compared between the 72 patients who died within one year after curative gastrectomy (the early recurrence group) and the 92 patients who died 3 years after curative gastrectomy (the late recurrence group). RESULTS: Compared with the late recurrence group, the early recurrence group showed an older age, a more advanced stage, a poorly differentiated type of cancer and a significantly higher tendency to have lymphatic invasion, vascular invasion and perineural invasion.Especially in the gastric cancer patients with a more advanced stage (stage III and IV), the early recurrence group was characterized by a significantly higher preoperative serum carcino embryonic antigen level, perineural invasion and a relatively small number of dissected lymph nodes. CONCLUSIONS: The clinicopathologic characteristics of recurrent gastric cancer are significantly different according to the stage of disease, and even in the same stage. For the early detection of recurrence after curative surgery, it is important to recognize the clinicopathological factors that foretell a high risk of recurrence. It is mandatory to make an individualized surveillance schedule according to the clinicopathologic factors. PMID- 22076202 TI - Synchronous Adenocarcinoma and Gastrointestinal Stromal Tumor of the Stomach Treated by a Combination of Laparoscopy-assisted Distal Gastrectomy and Wedge Resection. AB - The simultaneous occurrence of a gastrointestinal stromal tumor (GIST) and a gastric adenocarcinoma is uncommon, and has rarely been reported in the literature. The present report describes the case of a 74-year-old male patient who initially presented with an adenocarcinoma that had invaded the antral mucosa. Computed tomography then revealed the presence of a suspected GIST, in the form of a 2*2 cm mass at the hilum of the spleen. In view of the advanced age of the patient, a surgical approach that would minimize risk and maximize quality of life was preferred. The patient therefore underwent simultaneous laparoscopy assisted distal gastrectomy for the adenocarcinoma and wedge resection for the GIST. This approach was only chosen after confirming that it would be possible to preserve three or more of the short gastric arteries that supply the area below the wedge resection site. This may be considered a feasible approach to the management of the simultaneous occurrence of a mid-to-low gastric body adenocarcinoma and a high gastric body GIST. PMID- 22076203 TI - An Insufficient Preoperative Diagnosis of Borrmann Type 4 Gastric Cancer in Spite of EMR. AB - Borrmann type 4 gastric cancers are notorious for the difficulty of finding cancer cells in the biopsy samples obtained from gastrofiberscopy. It is important to obtain the biopsy results for making surgical decisions. In cases with Borrmann type 4 gastric cancer, even though the radiological findings (such as an upper gastrointestinal series, abdominal computed tomography and positron emission tomography/computed tomography) or the macroscopic findings of a gastrofiberscopy examination imply a high suspicion of cancer, there can be difficulty in getting the definite pathologic results despite multiple biopsies. In these cases, we have performed endoscopic mucosal resection under gastrofiberscopy as an alternative to simple biopsies. Here we report on a case in which no cancer cells were found even in the endoscopic mucosal resection specimen, but the radiologic evidence and clinical findings were highly suspicious for gastric cancer. The patient finally underwent total gastrectomy with lymph node resection, and she was pathologically diagnosed as having stage IV gastric cancer postoperatively. PMID- 22076204 TI - Intrahepatic splenosis mimicking liver metastasis in a patient with gastric cancer. AB - A 54 year old man was referred to our hospital with gastric cancer. The patient had a history of splenectomy and a left nephrectomy as a result of a traffic accident 15 years earlier. The endoscopic findings were advanced gastric cancer at the lower body of the stomach. Abdominal ultrasonography (USG) and magnetic resonance imaging demonstrated a metastatic nodule in the S2 segment of the liver. Eventually, the clinical stage was determined to be cT2cN1cM1 and a radical distal gastrectomy, lateral segmentectomy of the liver were performed. The histopathology findings confirmed the diagnosis of intrahepatic splenosis, omental splenosis. Hepatic splenosis is not rare in patients with a history of splenic trauma or splenectomy. Nevertheless, this is the first report describing a patient with gastric cancer and intrahepatic splenosis that was misinterpreted as a liver metastatic nodule. Intra-operative USG guided fine needle aspiration should be considered to avoid unnecessary liver resections in patients with a suspicious hepatic metastasis. PMID- 22076205 TI - Gold-mediated bifunctional modification of oligosaccharides via a three-component coupling reaction. AB - An efficient modular approach for single-site incorporation of two independent functionalities (amines and alkynes) into aldehyde-containing oligosaccharides concurrently by using a one-pot gold-mediated three-component coupling reaction in aqueous medium under mild conditions has been developed. PMID- 22076206 TI - Clinicopathological features and surgical treatment of gastric cancer in South Korea: the results of 2009 nationwide survey on surgically treated gastric cancer patients. AB - PURPOSE: In an effort to examine the clinicopathological characteristics of GC and the status of its surgical treatment, the Korean Gastric Cancer Association (KGCA) conducted a nationwide survey targeting surgically-treated gastric cancer patients in 2009. MATERIALS AND METHODS: A standardized electrical case report was sent to every member institution of the KGCA via E-mail with detailed instructions regarding the survey data. Completed data forms were retrieved from each institution and analyzed by the KGCA information committee. RESULTS: Data on 14,658 patients was collected from 59 institutions. The mean patient age was 59.2+/-11.9 years with a male to female ratio of 2.05 : 1. Lower third cancer (56.0%) was the most common among all gastric cancers. The histological type revealed poorly differentiated adenocarcinoma (34.1%) to be the most common, and the Lauren classification revealed the intestinal type (50.0%) to be the most prevalent. Curative surgery was performed in 92.4% of patients with laparoscopic surgery in 25.8% of patients. A Billroth I reconstruction was performed most frequently after a distal gastrectomy (63.4% of distal gastrectomy). T1 cancers accounted for 57.6% of all cases, and 62.6% of patients showed no lymph node metastasis. Compared to previous reports, it was found that patients are becoming older, laparoscopic surgery is being performed increasingly, and the proportion of T1 cancer is increasing with time. CONCLUSIONS: This survey presented the clinicopathological characteristics and current status of the surgical treatment of gastric cancer in Korea. This survey is expected aid research studies as well as planning and evaluation programs targeting cancer control. PMID- 22076207 TI - Evaluation of the 7th UICC TNM Staging System of Gastric Cancer. AB - Since January of 2010, the seventh edition of UICC tumor node metastasis (TNM) Classification, which has recently been revised, has been applied to almost all cases of malignant tumors. Compared to previous editions, the merits and demerits of the current revisions were analyzed. Many revisions have been made for criteria for the classification of lymph nodes. In particular, all the cases in whom the number of lymph nodes is more than 7 were classified as N3 without being differentiated. Therefore, the coverage of the N3 was broad. Owing to this, there was no consistency in predicting the prognosis of the N3 group. By determining the positive cases to a distant metastasis as TNM stage IV, the discrepancy in the TNM stage IV compared to the sixth edition was resolved. In regard to the classification system for an esophagogastric (EG) junction carcinoma, it was declared that cases of an invasion to the EG junction should follow the classification system for esophageal cancer. A review of clinical cases reported from Asian patients suggests that it would be more appropriate to follow the previous editions of the classification system for gastric cancer. In addition, in the classification of the TNM stages in the overall cases, the discrepancy in the prognosis between the different stages and the consistency in the prognosis between the same TNM stages were achieved to a lesser extent as compared to that previously. Accordingly, further revisions are needed to develop a purposive classification method where the prognosis can be predicted specifically to each variable and the mode of the overall classification can be simplified. PMID- 22076208 TI - Clinical significance of the pattern of lymph node metastasis depending on the location of gastric cancer. AB - PURPOSE: When performing a laparoscopic assisted gastrectomy, a function preserving gastrectomy is performed depending on the location of the primary gastric cancer. This study examined the incidence of lymph node metastasis by the lymph node station number by tumor location to determine the optimal extent of the lymph node dissection. MATERIALS AND METHODS: The subjects consisted of 1,510 patients diagnosed with gastric cancer who underwent a gastrectomy between 1996 and 2005. The patients were divided into three groups: upper, middle and lower third, depending on the location of the primary tumor. The lymph node metastasis patterns were analyzed in the total and early gastric cancer patients. RESULTS: In all patients, lymph node station numbers 1, 2, 3, 7, 10 and 11 metastases were dominant in the cancer originating in the upper third, whereas station numbers 4, 5, 6 and 8 were dominant in the lower third. In early gastric cancer patients, the station number of lymph nodes with a metastasis did not show a significant difference in stage pT1a disease. On the other hand, a metastasis in lymph node station number 6 was dominant in stage pT1b disease that originated in the lower third of the stomach. CONCLUSIONS: When performing a laparoscopic-assisted gastrectomy for early gastric cancer, a limited lymphadenectomy is considered adequate during a function-preserving gastrectomy in mucosal (T1a) cancer. On the other hand, for submucosal (T1b) cancer, a number 6 node dissection should be performed when performing a pylorus preserving gastrectomy. PMID- 22076209 TI - Evaluation of the 7th AJCC TNM Staging System in Point of Lymph Node Classification. AB - PURPOSE: The 7th AJCC tumor node metastasis (TNM) staging system modified the classification of the lymph node metastasis widely compared to the 6th edition. To evaluate the prognostic predictability of the new TNM staging system, we analyzed the survival rate of the gastric cancer patients assessed by the 7th staging system. MATERIALS AND METHODS: Among 2,083 patients who underwent resection for gastric cancer at the department of surgery, Hanyang Medical Center from July 1992 to December 2009, This study retrospectively reviewed 5-year survival rate (5YSR) of 624 patients (TanyN3M0: 464 patients, TanyNanyM1: 160 patients) focusing on the number of metastatic lymph node and distant metastasis. We evaluated the applicability of the new staging system. RESULTS: There were no significant differences in 5YSR between stage IIIC with more than 29 metastatic lymph nodes and stage IV (P=0.053). No significant differences were observed between stage IIIB with more than 28 metastatic lymph nodes and stage IV (P=0.093). Distinct survival differences were present between patients who were categorized as TanyN3M0 with 7 to 32 metastatic lymph nodes and stage IV. But patients with more than 33 metastatic lymph nodes did not show any significant differences compared to stage IV (P=0.055). Among patients with TanyN3M0, statistical significances were seen between patients with 7 to 30 metastatic lymph nodes and those with more than 31 metastatic lymph nodes. CONCLUSIONS: In the new staging system, modifications of N classification is mandatory to improve prognostic prediction. Further study involving a greater number of cases is required to demonstrate the most appropriate cutoffs for N classification. PMID- 22076210 TI - Feasibility study of early oral intake after gastrectomy for gastric carcinoma. AB - PURPOSE: Despite the compelling scientific and clinical data supporting the use of early oral nutrition after major gastrointestinal surgery, traditional bowel rest and intravenous nutrition for several postoperative days is still being used widely after gastric cancer surgery. MATERIALS AND METHODS: A phase II study was carried out to evaluate the feasibility and safety of postoperative early oral intake (water intake on postoperative days (POD) 1-2, and soft diet on POD 3) after a gastrectomy. The primary outcome was morbidity within 30 postoperative days, which was targeted at <25% based on pilot study data. RESULTS: The study subjects were 90 males and 42 females with a mean age 61.5 years. One hundred and four (79%) and 28 (21%) patients underwent a distal and total gastrectomy, respectively. The postoperative morbidity rate was within the targeted range (15.2%, 95% CI, 10.0~22.3%), and there was no hospital mortality. Of the 132 patients, 117 (89%) successfully completed a postoperative early oral intake regimen without deviation; deviation in 10 (8%) due to gastrointestinal symptoms and in five (4%) due to the management of postoperative complications. The mean times to water intake and a soft diet were 1.0+/-0.2 and 3.2+/-0.7 days, respectively, and the mean hospital stay was 10.0+/-6.1 days. CONCLUSIONS: Postoperative early oral intake after a gastrectomy is feasible and safe, and can be adopted as a standard perioperative care after a gastrectomy. Nevertheless, further clinical trials will be needed to evaluate the benefits of early oral nutrition after upper gastrointestinal surgery. PMID- 22076211 TI - Efficacy of endoscopic ultrasonography for prediction of tumor depth in gastric cancer. AB - PURPOSE: As the proportion of early gastric cancer (EGC) has recently been increased, minimally invasive treatment is currently accepted as main therapy for EGC. Accurate preoperative staging is very important in determining treatment options. To know the accuracy of endoscopic ultrasonography (EUS), we compared the depth of invasion of the tumor with preoperative EUS and postoperative pathologic findings. MATERIALS AND METHODS: We retrospectively analyzed 152 patients who underwent EUS before laparoscopic gastrectomy. The preoperative EUS results were compared with the pathological findings. RESULTS: The overall proportion of coincidence for depth of invasion between EUS and pathologic results was 41.4%. Univariate analysis showed that the rate of corrected prediction of EUS for tumor depth significantly decreased for the lesions more than 3cm in diameter (P=0.033), and those with a depressed morphology (P=0.035). In multivariate analysis, the depressed type (P=0.029, OR=2.873) and upper lesion (P=0.035, OR=2.151) was the significantly independent factors influencing the inaccurate prediction of EUS for tumor depth. CONCLUSIONS: When we decide the treatment modality considering the clinical depth of invasion by EUS, the possibility of discordance with pathologic results should be considered for the lesions located in the upper third of the stomach and with a depressed morphology. PMID- 22076213 TI - Mixed exocrine and endocrine carcinoma in the stomach: a case report. AB - We report a rare case of the coexistence of a gastric small cell neuroendocrine carcinoma with a gastric adenocarcinoma. A 62-year-old man presented with epigastric soreness for 1 month. Esophagogastroduodenoscopy revealed a Borrmann type I tumor at the lesser curvature of the lower body of the stomach. The patient underwent a distal gastrectomy with D2 lymph node dissection and the resected specimen exhibited a 3.5*3.5 cm sized, fungating lesion. Two separated, not intermingling, lesions with non-adenocarcinoma components encircled by well differentiated adenocarcinoma components were identified microscopically. The non adenocarcinoma component showed neuroendocrine features, such as a solid and trabecular pattern, and the tumor cells showed a high nuclear grade with minimal cytoplasm, indistinct nucleoli, and positive response for synaptophysin, CD56. The final pathological diagnosis was a gastric mixed exocrine-endocrine carcinoma (MEEC) composed of an adenocarcinoma and small cell neuroendocrine carcinoma of the collision type. PMID- 22076212 TI - Operative risk factors in gastric cancer surgery for elderly patients. AB - PURPOSE: Gastric cancer surgery is a common operation in East Asia, such as Korea and Japan, and there has been a significant increase in the need for this procedure due to the aging population. As a result, surgery for the treatment of gastric cancer for elderly patients is expected to increase. This study examined the effect of old age on gastric cancer surgery, and analyzed the operative risk factors for elderly patients. MATERIALS AND METHODS: From November 2008 to August 2010, 590 patients, who underwent a curative resection for gastric cancers, were enrolled. Patients who underwent palliative or emergency surgery were excluded. A retrospective analysis of the correlation between surgical outcomes and age was performed. The elderly were defined as patients who were over the age of 65 years. RESULTS: The mean age of all patients was 58.3 years, and complications occurred in 87 cases (14.7%). The most common complication was wound infection and severe complications requiring surgical, endoscopic, or radiologic intervention developed in 52 cases (8.8%). The rate of complications increased with increasing age of the patients. Univariate analysis revealed age, comorbidity, extent of resection, operation time, and combined resection to be associated with surgical complications. In particular, age over 75 years old, operation time, and comorbidity were predictive factors in multivariate analysis. In the elderly, only comorbidity was associated with surgical complications. CONCLUSIONS: The patients' age is the most important factor for predicting surgical complications. Surgeons should pay an attention to the performance of gastric cancer surgery on elderly patients. In particular, it must be performed carefully for elderly patients with a comorbidity. PMID- 22076214 TI - Composite neuroendocrine carcinoma with adenocarcinoma of the stomach misdiagnosed as a giant submucosal tumor. AB - A composite glandular/exocrine-endocrine carcinoma of the gastrointestinal tract is characterized by the co-existence of two adjacent, but histologically-distinct tumors in an organ. Composite glandular/exocrine-endocrine carcinomas are a special type of tumor comprised of common adenocarcinomas and neuroendocrine components that account for at least one-third of the entire tumor area. Composite tumors have been reported in a range of organs, but are relatively rare in the stomach. We report a case of a composite neuroendocrine carcinoma with an adenocarcinoma of the stomach (mixed exocrine-endocrine carcinoma), which was misdiagnosed as a giant submucosal tumor preoperatively based on esophagogastroduodenoscopy and a contrast-enhanced axial computed tomographic scan. PMID- 22076215 TI - Laparoscopic gastric wedge resection and prophylactic antireflux surgery for a submucosal tumor of gastroesophageal junction. AB - A laparoscopic wedge resection for a submucosal tumor, which is close to the gastroesophageal junction, is technically challenging. This can be a dilemma to both patients and surgeons when the tumor margin involves the gastroesophageal junction because a wedge resection in this situation might result in a deformity of the gastroesophageal junction or an injury to the lower esophageal sphincter, which ultimately results in lifelong gastroesophageal reflux disease. The patient was a 42 year-old male, whose preoperative endoscopic ultrasonographic finding did not rule out a gastrointestinal stromal tumor. He underwent a laparoscopic gastric wedge resection and prophylactic anterior partial fundoplication (Dor) and was discharged from hospital on the fifth postoperative day without any complications. There were no symptoms of reflux 5 months after surgery. A laparoscopic wedge resection and prophylactic anti-reflux surgery might be a good surgical option for a submucosal tumor at the gastroesophageal junction. PMID- 22076216 TI - Prospective evaluation of supportive care with or without CVD chemotherapy as a second-line treatment in advanced melanoma by patient's choice: a multicentre Dermatologic Cooperative Oncology Group trial. AB - This prospective, nonrandomized multicentre, phase III study compared best supportive care (BSC) alone with cisplatin, vindesine and dacabazine-based (CVD) chemotherapy and BSC in patients with advanced melanoma. A total of 117 pretreated patients with metastatic melanoma were evaluated, 34 patients in arm A (BSC) and 83 in arm B (BSC and CVD). Primary endpoint was overall survival and secondary endpoints were disease control rate and quality of life (European Organisation for Research and Treatment of Cancer QLQ-C30). Owing to sparse recruitment of patients for randomization, the protocol has been changed based on patients' choice. Baseline characteristics were imbalanced with respect to the Karnofsky Performance Index (P=0.001), the existence of brain metastases (P=0.035) and earlier application of chemoimmunotherapy (P=0.038). Disease control was observed in 8.8% of patients in arm A and in 28.9% of patients in arm B (P=0.028). Median overall survival time was 137 days in arm A and 229 days in arm B (P=0.014). Multivariate analyses could not ascribe this prognostic benefit to CVD treatment. No significant difference in the quality of life could be found. This study could not detect clear survival benefits for polychemotherapy with CVD compared with BSC alone in patients with advanced metastatic melanoma. Interestingly, having the choice of chemotherapy or BSC alone in a second-line situation, more than 70% of patients chose polychemotherapy. PMID- 22076217 TI - Gastric cancer epidemiology in Korea. AB - Gastric cancer has been the most commonly diagnosed cancer in Korea although the age-standardized mortality and incidence has decreased gradually during last two decades. Helicobacter pylori infection and cigarette smoking are well-established risk factors, and the role of dietary factors, such as salted foods, fresh vegetables and fruits, soy foods, and processed or grilled meats on gastric carcinogenesis has been suggested. In this review, we review national and international gastric cancer statistics, studies on environmental risk factors conducted in the Korean population, and gastric cancer screening activities. PMID- 22076218 TI - Interobserver Variation in the Diagnosis of Gastric Epithelial Dysplasia and Carcinoma between Two Pathologists in Japan and Korea. AB - Although the biological potential of gastric epithelial dysplasia (GED) as a precursor of gastric cancer has never been in doubt, the classification of these lesions has been controversial and fraught with marked variations in approach to diagnosis across the world. The complexity of cyto-architectural features has been considered to be of paramount importance for the diagnosis of carcinoma in Japan, while breach of the basement membrane and invasion into the lamina propria has been considered the sine qua non of malignancy and hence a pre-requisite for the diagnosis of cancer in the West. In Korea, although the incidence of gastric cancer is similar to Japan, the diagnostic approach to GED or cancer seems to lie midway between Western and Japanese criteria. In this review, we will discuss the difference in the diagnosis of GED and cancer between two pathologists working in the comprehensive cancer center located in Japan and Korea, one of the most prevalent areas in the world for gastric cancer. PMID- 22076219 TI - Endoscopic treatment for early gastric cancer. AB - Endoscopic resection has been accepted as a curative modality for early gastric cancer (EGC). Since conventional endoscopic mucosal resection (EMR) has been introduced, many improvements in endoscopic accessories and techniques have been achieved. Recently, endoscopic submucosal dissection (ESD) using various electrosurgical knives has been performed for complete resection of EGC and enables complete resection of EGC, which is difficult to completely resect in the era of conventional EMR. Currently, ESD is accepted as the standard method for endoscopic resection of EGC in indicated cases. In this review, the history of endoscopic treatment for EGC, overall ESD procedures, and indications and clinical results of endoscopic treatment will be presented. PMID- 22076220 TI - Frozen Section Biopsy to Evaluation of Obscure Lateral Resection Margins during Gastric Endoscopic Submucosal Dissection for Early Gastric Cancer. AB - PURPOSE: To determine the diagnostic utility of a frozen section biopsy in patients undergoing endoscopic submucosal dissection (ESD) for early gastric neoplasms with obscure margins even with chromoendoscopy using acetic acid and indigo carmine (AI chromoendoscopy). MATERIALS AND METHODS: The lateral spread of early gastric neoplasms was unclear even following AI chromoendoscopy in 38 patients who underwent ESD between June 2007 and May 2011. Frozen section biopsies were obtained by agreement of the degree of lateral spread between two endoscopists. Thus, frozen section biopsies were obtained from 23 patients (FBx group) and not in the other 15 patients (AI group). RESULTS: No significant differences were observed for size, histology, invasive depth, and location of lesions between the AI and FBx groups. No false positive or false negative results were observed in the frozen section diagnoses. Adenocarcinoma was revealed in three patients and tubular adenoma in one, thereby changing the delineation of lesion extent and achieving free lateral margins. The rates of free lateral resection margins and curative resection were significantly higher in the FBx group than those in the AI group. CONCLUSIONS: Frozen section biopsy can help endoscopists perform more safe and accurate ESD in patients with early gastric neoplasm. PMID- 22076221 TI - Clinical Outcomes of Gastrectomy after Incomplete EMR/ESD. AB - PURPOSE: Endoscopic resection is widely accepted as standard treatment for early gastric cancer (EGC) without lymph node metastasis. The procedure is minimally invasive, safe, and convenient. However, surgery is sometimes needed after endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) due to perforation, bleeding, or incomplete resection [corrected]. We evaluated the role of surgery after incomplete resection. MATERIALS AND METHODS: We retrospectively studied 29 patients with gastric cancer who underwent a gastrectomy after incomplete EMR/ESD from 2006 to 2010 at Korea University Hospital. RESULTS: There were 13 incomplete resection cases, seven bleeding cases, three metachronous lesion cases, three recurrence cases, two perforation cases, and one lymphatic invasion case. Among the incomplete resection cases, a positive vertical margin was found in 10, a positive lateral margin in two, and a positive vertical and lateral margin in one case. Most cases (9/13) were diagnosed as mucosal tumors by endoscopic ultrasonography, but only three cases were confirmed as mucosal tumors on final pathology. The positive residual tumor rate was two of 13. The lymph node metastasis rate was three of 13. All lymph node metastasis cases were submucosal tumors with positive lymphatic invasion and no residual tumor in the gastrectomy specimen. No cases of recurrence were observed after curative resection. CONCLUSIONS: A gastrectomy is required for patients with incomplete resection following EMR/ESD due to the risk of residual tumor and lymph node metastasis. PMID- 22076222 TI - Clinical outcomes according to primary treatment in gastric cancer patients with peritoneal seeding. AB - PURPOSE: Peritoneal seeding of gastric cancer is known to have a poor prognosis. With the diagnosis of peritoneal seeding, there is no effective treatment modality. Gastrectomy with chemotherapy or primary chemotherapy is basically one of major options for this condition. This study was conducted to compare the clinical outcomes of these treatments and to identify the better way to improve the prognosis of patients with peritoneal seeding. MATERIALS AND METHODS: Between 2001 and 2007, gastric cancer patients with peritoneal seeding by preoperative or intraoperative diagnosis were reviewed retrospectively. The enrolled patients were divided as primary gastrectomy and primary chemotherapy group. Clinicopathologic characteristics and clinical outcomes of groups were analyzed and compared. RESULTS: Fifty-four patients were enrolled. 21 patients belonged to the group of primary gastrectomy and 33 patients were to the primary chemotherapy group. Among 33 patients of the primary chemotherapy group, 17 patients were received only chemotherapy and 16 patients were received gastrectomy due to the good responses of primary chemotherapy. The 3 years survival rates were 14% in primary gastrectomy group, 55% in patients who received gastrectomy after primary chemotherapy, and 0% in patients with primary chemotherapy only. CONCLUSIONS: Although this study had many limitations, some valuable information was produced. In terms of survival benefits for the gastric cancer patients with peritoneal seeding, primary gastrectomy and additional gastrectomy after primary chemotherapy revealed the better clinical outcomes. But, prospective randomized clinical study and multi-center study should be performed to decide proper treatment for gastric cancer patients with peritoneal seeding [corrected]. PMID- 22076223 TI - Role of F-fluoro-2-deoxyglucose Positron Emission Tomography in Gastric GIST: Predicting Malignant Potential Pre-operatively. AB - PURPOSE: It is difficult to obtain biopsies from gastrointestinal stromal tumors (GISTs) prior to surgery because GISTs are submucoal tumors, despite being the most common nonepithelial neoplasms of the gastrointestinal tract. Unlike anatomic imaging techniques, PET-CT, which is a molecular imaging tool, can be a useful technique for assessing tumor activity and predicting the malignant potential of certain tumors. Thus, we aimed to evaluate the usefulness of PET-CT as a pre-operative prognostic factor for GISTs by analyzing the correlation between the existing post-operative prognostic factors and the maximum SUV uptake (SUVmax) of pre-operative 18F-fluoro-2-deoxyglucose (FDG) PET-CT. MATERIALS AND METHODS: The study was conducted on 26 patients who were diagnosed with gastric GISTs and underwent surgery after being examined with pre-operative FDG PET-CT. An analysis of the correlation bewteen (i) NIH risk classfication and the Ki-67 proliferation index, which are post-operative prognostic factors, and (ii) the SUVmax of PET-CT, which is a pre-operative prognostic factor, was performed. RESULTS: There were significant correlations between (i) SUVmax and (ii) Ki-67 index, tumor size, mitotic count, and NIH risk group (r=0.854, 0.888, 0.791, and 0.756, respectively). The optimal cut-off value for SUVmax was 3.94 between "low risk malignancy" and "high-risk malignancy" groups. The sensitivity and specificity of SUVmax for predicting the risk of malignancy were 85.7% and 94.7%, respectively. CONCLUSIONS: The SUVmax of PET-CT is associated with Ki-67 index, tumor size, mitotic count, and NIH classification. Therefore, it is believed that PET-CT is a relatively safe, non-invasive diagnostic tool for assessing malignant potential pre-operatively. PMID- 22076224 TI - An effect of letrozole on gastric cancer? AB - Letrozole is a drug used in the treatment of postmenopausal women with breast and ovarian tumours. There is no evidence in the literature indicating its use in treating gastric cancer. We present a 68 year old lady admitted from the emergency department with weight loss, malaise and anaemia. Investigations confirmed the presence of two different primary tumours in the left breast and the stomach. Following that this patient with oestrogen receptor positive breast cancer and oestrogen receptor negative gastric cancer was treated with letrozole for her breast cancer followed by a gastric resection. Independent histology by two pathologists pre-operatively diagnosed gastric adenocarcinoma. Post operatively, independent analysis of the resected stomach, omentum and lymph nodes revealed no evidence of gastric cancer. Therefore we conclude that there is a possibility of letrozole having an effect on gastric cancer. Further studies are needed. PMID- 22076225 TI - Acute gastric necrosis due to gastric outlet obstruction accompanied with gastric cancer and trichophytobezoar. AB - Gastric necrosis due to gastric outlet obstruction is a very rare condition, but it might be fatal if missed or if diagnosis is delayed. Our patient was a 73-year old male complaining of abdominal pain, distension and dyspnea for 1 day. In plain radiography and computed tomography, a markedly distended stomach and decreased enhancement at the gastric wall were noted. He underwent explo laparotomy, and near-total gastric mucosal necrosis accompanied by sludge from the soaked laver was noted. A total gastrectomy with esophagojejunostomy was performed, and he recovered without sequelae. Final pathologic examination revealed advanced gastric cancer at the antrum with near-total gastric mucosal necrosis. PMID- 22076226 TI - Early gastric cancer with signet ring cell histology remained unresected for 53 months. AB - The natural course of untreated patients with signet ring cell carcinoma of the stomach remains poorly understood while assumptions have been made to distinguish it from other types of gastric cancer. A 74-year-old Korean woman was diagnosed with early gastric cancer with signet ring cell histology and refused surgery. A satellite lesion was identified 46 months after the initial diagnosis. The patient finally agreed to undergo distal subtotal gastrectomy 53 months following the initial diagnosis. Postoperative histological examination of both lesions confirmed signet ring cell carcinoma associated with submucosal invasion. There was no evidence of lymph node metastasis. PMID- 22076227 TI - Glucose-regulated protein 78 positivity as a predictor of poor survival in patients with renal cell carcinoma. AB - INTRODUCTION: Glucose-regulated protein 78 (GRP78), a chaperone for newly formed proteins during folding and glycosylation, is associated with resistance to apoptosis in some forms of cancer. We assessed GRP78 expression and its correlation with clinicopathological parameters and survival. PATIENTS AND METHODS: Immunohistochemistry was performed using formalin-fixed, paraffin embedded specimens: 128 primary renal cell carcinoma (RCC) specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. GRP78 positivity was determined based on intensity of staining and percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters including patients' survival was evaluated. RESULTS: A statistically significant association was found between GRP78 positivity and higher tumor grade (G3; p <0.0001), advanced T stage (>=pT3; p = 0.0002), lymphovascular invasion (positive; p <0.0001), regional nodal involvement (>=N1; p = 0.0086), and distant metastases at presentation (M1; p = 0.001). Positivity of GRP78 expression was significantly associated with shorter disease-specific survival and shorter progression-free survival. Cox proportional hazard model showed that strong GRP78 positivity was an independent predictor of shortened progression-free survival in N0M0 RCC patients. CONCLUSIONS: There was a significant relationship between GRP78 expression levels and aggressiveness of RCC. Increased expression of GRP78 might be a useful parameter to predict shortened survival in patients with RCC. PMID- 22076229 TI - Prevalence and related risk behaviors of HIV, syphilis, and anal HPV infection among men who have sex with men from Beijing, China. AB - Specific risk behaviors related to different sexually transmitted infections have not been widely evaluated among men who have sex with men in China. In the present study, a total of 302 MSM were recruited from Beijing with a prevalence of HIV, syphilis, and anal HPV infection as 9.9, 19.2 and 71.4%, respectively. Lower education level was observed to be related to higher infection rate of HIV and syphilis. "Ever found sexual partners in gay venues" was significantly associated with HIV infection as well. "Taking anilinction as regular sexual behavior" was observed to be a significant predictor for anal HPV infection. PMID- 22076230 TI - Take the wind out of asthma. AB - A common cause of emergency department visits, asthma is on the rise. Find out how to keep patients breathing easy. PMID- 22076233 TI - Propofol. PMID- 22076234 TI - A multidisciplinary care approach to Guillain-Barre syndrome. AB - Guillain-Barre syndrome (GBS) is a complicated degenerative disorder. Its etiology is unclear, although it has been associated with both cell and humoral mediated autoimmune mechanisms. The disease causes ascending paralysis and loss of cranial nerve function. Manifestations may be acute or chronic, and temporary or permanent, depending on the degree of neuronal destruction. Because of GBS's pervasive nature, health care is a challenge. Patient care focuses on risks related to ineffective airway clearance and impaired mobility. Psychosocial care and patient education are also integral components of care. PMID- 22076236 TI - The role of beta-blockers in the management of patients with heart failure. AB - More than 400,000 new cases of heart failure are diagnosed each year, making it one of the largest problems in health care today, particularly among the elderly. Primary care providers must be aware of the benefits of early recognition and treatment of heart failure and asymptomatic left ventricular systolic dysfunction. Standard therapy has included ACE inhibitors, digoxin, and diuretics for volume overload. More recently, large clinical trials have prompted the recommendation to add beta-blockers to this regimen. This article reviews heart failure pathophysiology, management, and the consensus recommendations for adding beta-blockers to heart failure therapy. PMID- 22076237 TI - Need critical care nurses? Inquire within. AB - A serious shortage of critical care nurses encouraged a nurse-manager to develop intensive care unit nurses through an innovative preceptor program. PMID- 22076238 TI - Nurses and informed consent, part 1. PMID- 22076239 TI - Family advocates: caring for families in crisis. AB - Families of patients unexpectedly brought to the emergency department or transferred to the intensive care unit are families in crisis. In the greater scheme of things, they may not be a priority. This article discusses a program in which family advocates care for families just as nurses and physicians care for the critically ill patient. PMID- 22076241 TI - Should continuous lateral rotation therapy replace manual turning? AB - Continuous lateral rotation therapy (CLRT) has been proposed as a replacement for standard manual turning to decrease pulmonary complications in critically ill patients. Findings on the effectiveness of CLRT in decreasing pulmonary complications are promising, but some serious gaps exist, such as when to start and end therapy. This article reviews and analyzes the research on CLRT and proposes directions for future research. PMID- 22076242 TI - Dealing with medical futility. PMID- 22076243 TI - Preparation of a composite fibrous membrane loaded with mesalazine and metronidazole by interlaced electrospinning. AB - Novel composite fibrous membranes loaded with mesalazine and metronidazole were fabricated via interlaced electrospinning. The fibers were characterized by scanning electron microscopy and FTIR transmission spectra techniques. These characterizations were performed in the aim of optimizing the experimental conditions which allowed us to obtain good morphology of fibrous membrane loaded drugs. The in vitro release experiments revealed that mesalazine and metronidazole were released continuously from the loaded drug fibrous membrane. The fibrous membrane-loaded drugs also showed excellent stability. Compared to those of other drug delivery systems, the main advantage of these two fibrous membrane-loaded drugs is that they can be directly implanted as a lesion after surgery to inhibit recurrence in Crohn's disease. PMID- 22076244 TI - Selective cell cycle arrest and induction of apoptosis in human prostate cancer cells by a polyphenol-rich extract of Solanum nigrum. AB - Progression of prostate cancer is associated with escape of tumor cells from cell cycle arrest and apoptosis. Agents capable of selectively eliminating cancer cells by cell cycle arrest and/or induction of apoptosis offer a highly desirable approach. Here we demonstrate that a polyphenolic extract derived from ripe berries of Solanum nigrum (SN) differentially causes cell cycle arrest and apoptosis in various human prostate cancer cells without affecting normal prostate epithelial cells. Virally transformed normal human prostate epithelial PZ-HPV-7 cells and their cancer counterpart CA-HPV-10 cells, were used to evaluate the growth-inhibitory effects of the SN extract. SN treatment (5-20 ug/ml) of PZ-HPV-7 cells resulted in growth inhibitory responses of low magnitude. In sharp contrast, SN treatment of CA-HPV-10 cells increased cytotoxicity, decreased cell viability and induced apoptosis. Similar results were noted in the human prostate cancer LNCaP, 22Rv1, DU145 and PC-3 cell lines, where significant reductions in cell viability and induction of apoptosis was observed in all these cells, an effect independent of disease stage and androgen association. Cell cycle analysis revealed that SN treatment (5-20 ug/ml) resulted in a dose-dependent G2/M phase arrest and subG1 accumulation in the CA-HPV-10 but not in the PZ-HPV-7 cell line. Our results, for the first time, demonstrate that the SN extract is capable of selectively inhibiting cellular proliferation and accelerating apoptotic events in prostate cancer cells. SN may be developed as a promising therapeutic and/or preventive agent against prostate cancer. PMID- 22076245 TI - Effects of alcohol (BAC 0.50/00) and ecstasy (MDMA 100 mg) on simulated driving performance and traffic safety. AB - RATIONAL: An increasing number of fatal road-accidents have been reported in which ecstasy was found in the blood of drivers. Although, ecstasy is frequently found to have been used in combination with alcohol, studies on the acute effects of ecstasy co-administered with alcohol on driving performance are relatively rare. OBJECTIVE: The present study was designed to establish the extent of driver impairment as a consequence of ecstasy or combined ecstasy and alcohol use as compared to driving under the influence of 0.30/00, 0.50/00 and 0.80/00 alcohol. Furthermore, subjective performance was also assessed. RESULTS: Alcohol and ecstasy mainly influenced automated driving performance such as lateral and speed control. However, small to no effects of the substances were found on more complex driving behaviour. Overall, variance within the different driving measures was high especially when participants were treated with 3.4 methylenedioxy-methamphetamine (MDMA) and alcohol. Furthermore, equivalence testing showed that combined use may lead to impaired driving for some, but not all, drivers. Participants rated their own performance to be slightly worse than normal in both studies. Since driving was actually seriously deteriorated, this was a falsely positive assessment of their condition. CONCLUSIONS: The dissociation between subjective perceptions and objective performance decrements are important notions for traffic safety since this may affect a driver's judgement of whether or not it is safe to drive. For example, an intoxicated individual might decide to drive because the feelings of alertness caused by MDMA cloud the impairing effects of other drugs such as alcohol, thereby creating a potentially serious risk for traffic safety. PMID- 22076246 TI - Effects of dexamphetamine with and without alcohol on simulated driving. AB - RATIONALE: In party circuits dexamphetamine is frequently used in combination with alcohol. It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol, but may potentiate risk taking behaviour. OBJECTIVES: The study was aimed at assessing the effects of alcohol, dexamphetamine and the combination of both on simulated driving and cognitive performance. METHOD: Eighteen subjects participated in a randomized, crossover, placebo-controlled study employing four conditions: 10 mg dexamphetamine, 0.8 g/kg alcohol, 10 mg dexamphetamine + 0.8 g/kg alcohol, and placebo. Fundamental driving skills and risk-taking behaviour were assessed in a driving simulator. Subjects also completed vigilance and divided attention tasks, and subjective ratings. RESULTS: Mean BAC levels during simulated driving were between 0.910/00 and 0.640/00. Subjects using alcohol showed a significantly larger mean standard deviation of lateral position and shorter accepted gap time and distance. Use of alcohol or dexamphetamine + alcohol was associated with a higher frequency of red light running and collisions than the dexamphetamine or placebo conditions. Performance of vigilance and divided attention tasks was significantly impaired in the alcohol condition and, to a lesser degree, in the dexamphetamine + alcohol condition. CONCLUSION: Single doses of 0.8 g/kg alcohol increased risk-taking behaviours and impaired tracking, attention and reaction time during a 3-h period after drinking when BACs declined from 0.9 to 0.2 mg/ml. The stimulatory effects of co-administration of dexamphetamine 10 mg were not sufficient to overcome the impairing effects of alcohol on skills related to driving. PMID- 22076247 TI - Adsorptive loss of secreted recombinant proteins in transgenic rice cell suspension cultures. AB - Adsorptive loss of human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) in transgenic rice cell suspension cultures was investigated using glass flasks, plastic flasks, disposable vessels, and stainless steel vessels. When hCTLA4Ig was added to the glass flasks containing sterile AA medium, a rapid decrease in the concentration of hCTLA4Ig, independent on pH, was observed resulting in more than 90% of the protein loss within 1 h due to the surface adsorption. When the same experiments were performed on four different types of culture equipments mentioned above, the lowest adsorption level was observed in the plastic flasks and the highest level was observed in the glass flasks. The use of the plastic flasks retarded the adsorptive loss of hCTLA4Ig at the early stage of the protein production. There was a significant increase in the production of hCTLA4Ig when the flasks were coated with bovine serum albumin. However, the spike test of purified hCTLA4Ig at two different concentrations of 15 and 100 mg L(-1) in 500-mL spinner flasks confirmed that the amount of hCTLA4Ig adsorbed was dependent on the surface area of the flasks but not on the concentrations. In conclusion, although the protein adsorption affected the total amount of the protein yielded to some extent, it could be regarded as a minor factor in transgenic plant cell cultures with higher titer. PMID- 22076248 TI - Expansins are involved in cell growth mediated by abscisic acid and indole-3 acetic acid under drought stress in wheat. AB - Expansin protein is a component of the cell wall generally accepted to be the key regulator of cell wall extension during plant growth. Plant hormones regulate expansin gene expression as well as plant growth during drought stress. However, the relationship between expansin and plant hormone is far from clear. Here, we studied the involvement of expansin in plant cell growth mediated by the hormones indole-3-acetic acid (IAA) and abscisic acid (ABA) under osmotic stress which was induced by polyethylene glycol (PEG)-6000. Wheat coleoptiles from a drought resistant cultivar HF9703 and a drought-sensitive cultivar 921842 were used to evaluate cell growth and expansin activity. Osmotic stress induced the accumulation of ABA. ABA induced expansin activity mainly by enhancing expansin expression, since ABA induced cell wall basification via decreasing plasma membrane H(+)-ATPase activity, which was unfavorable for expansin activity. Although ABA induced expansin activity and cell wall extension, treatment with exogenous ABA and/or fluridone (FLU, an ABA inhibitor) suggested that ABA was involved in the coleoptile growth inhibition during osmotic stress. IAA application to detached coleoptiles also enhanced coleoptile growth and increased expansin activity, but unlike ABA, IAA-induced expansin activity was mainly due to the decrease of cell wall pH by increasing plasma membrane H(+)-ATPase activity. Compared with drought-sensitive cultivar, the drought-resistant cultivar could maintain greater expansin activity and cell wall extension, which was contributive to its resultant faster growth under water stress. PMID- 22076249 TI - Adrenergic stress reveals septal hypertrophy and proteasome impairment in heterozygous Mybpc3-targeted knock-in mice. AB - Hypertrophic cardiomyopathy (HCM) is characterized by asymmetric septal hypertrophy and is often caused by mutations in MYBPC3 gene encoding cardiac myosin-binding protein C. In contrast to humans, who are already affected at the heterozygous state, mouse models develop the phenotype mainly at the homozygous state. Evidence from cell culture work suggested that altered proteasome function contributes to the pathogenesis of HCM. Here we tested in two heterozygous Mybpc3 targeted mouse models whether adrenergic stress unmasks a specific cardiac phenotype and proteasome dysfunction. The first model carries a human Mybpc3 mutation (Het-KI), the second is a heterozygous Mybpc3 knock-out (Het-KO). Both models were compared to wild-type (WT) mice. Mice were treated with a combination of isoprenaline and phenylephrine (ISO/PE) or NaCl for 1 week. Whereas ISO/PE induced left ventricular hypertrophy (LVH) with increased posterior wall thickness to a similar extent in all groups, it increased septum thickness only in Het-KI and Het-KO. ISO/PE did not affect the proteasomal chymotrypsin-like activity or beta5-subunit protein level in Het-KO or wild-type mice (WT). In contrast, both parameters were markedly lower in Het-KI and negatively correlated with the degree of LVH in Het-KI only. In conclusion, adrenergic stress revealed septal hypertrophy in both heterozygous mouse models of HCM, but proteasome dysfunction only in Het-KI mice, which carry a mutant allele and closely mimic human HCM. This supports the hypothesis that proteasome impairment contributes to the pathophysiology of HCM. PMID- 22076250 TI - Transient diplopia with ipsilateral abducent nerve palsy and ptosis following a maxillary local anesthetic injection: a case report and review of literature. AB - BACKGROUND: The posterior superior alveolar (PSA) nerve block is commonly used in dentistry for treatment of the maxillary molars. Although this procedure is associated with many complications, ocular complications have been rarely reported. CASE REPORT: This report details an iatrogenic paresis of the abducent nerve and partial palsy of the oculomotor nerve leading to diplopia, strabismus and ptosis following a PSA nerve block and extraction of maxillary right second molar. The patient was treated symptomatically, and the recovery was uneventful. Relevant anatomical pathways with review of literature are discussed. DISCUSSION: Although rare, the dentist should be aware of these complications to avoid being perplexed by this unexpected circumstance, thus adversely affecting the doctor patient trust. PMID- 22076251 TI - The human sex odds at birth after the atmospheric atomic bomb tests, after Chernobyl, and in the vicinity of nuclear facilities: comment. AB - The recent claim made in this journal that nuclear bomb tests and the Chernobyl disaster caused distortions in the secondary sex ratio is shown to be a likely artifact of data mining, misused statistics, and misreading of the evidence. In particular, the concept of statistical "significance" and its limitations do not seem to be fully understood, and important confounding factors have not been accounted for. PMID- 22076252 TI - Quantitative structure-retention relationship for retention behavior of organic pollutants in textile wastewaters and landfill leachate in LC-APCI-MS. AB - INTRODUCTION: A quantitative structure-retention relation (QSRR) study was conducted on the retention times of organic pollutants in textile wastewaters and landfill leachate which was obtained by liquid chromatography-reversed phase atmospheric pressure chemical ionization-mass spectrometry. METHODS: The genetic algorithm was used as descriptor selection and model development method. Modeling of the relationship between selected molecular descriptors and retention time was achieved by linear (partial least square) and nonlinear (Levenberg-Marquardt artificial neural network, L-M ANN) methods. Linear and nonlinear models provide good results whereas more accurate results were obtained by the L-M ANN model. CONCLUSION: This is the first research on the QSRR of the organic pollutants in textile wastewaters and landfill leachate against the retention time. PMID- 22076254 TI - Exchange bias in iron oxide nanoclusters. AB - Iron oxide nanoclusters have been prepared by the gas-phase aggregation technique to form thin film structures with very high exchange bias values (up to 3000 Oe at low temperatures). Composition has been analysed by x-ray absorption and Mossbauer spectroscopies in order to elucidate the actual origin of the observed magnetic behaviour. The formation of a metal-oxide core-shell arrangement to explain the observed exchange bias has to be discarded since results show no metallic iron content and the main presence of alpha-Fe(2)O(3). The observed weak ferromagnetism and exchange bias are in agreement with the obtained size of alpha Fe(2)O(3) nanoparticles: weak ferromagnetism because of the well-known spin canting in this antiferromagnetic structure and exchange bias because of the interaction between different spin sublattice configurations promoted by the modification of iron coordination in alpha-Fe(2)O(3) nanoparticles. Moreover, the preparation method is proposed for tuning both magnetization and exchange bias values by modification of the preparation conditions of alpha-Fe(2)O(3) nanoparticles, which open new possibilities in the design of new materials with required properties. PMID- 22076253 TI - Uptake of a randomized breast cancer prevention trial comparing letrozole to placebo in BRCA1/2 mutations carriers: the LIBER trial. AB - Women with germline BRCA1 or BRCA2 (BRCA1/2) mutations are considered as an extreme risk population for developing breast cancer. Prophylactic mastectomy provides a valid option to reduce such risk, impacting however, the quality of life. Medical prevention by aromatase inhibitor that has also recently shown to have preventive effect may thus be considered as an alternative. LIBER is an ongoing double-blind, randomized phase III trial to evaluate the efficacy of 5 year letrozole versus placebo to decrease breast cancer incidence in post menopausal BRCA1/2 mutation carriers (NCT00673335). We present data on the uptake of this trial. We compared characteristics of women in the LIBER trial (n = 113) to those of women enrolled in the prospective ongoing national GENEPSO cohort (n = 1,505). Uptake was evaluated through a survey sent to all active centres, with responses obtained from 17 to the 20 (85%) centres. According to the characteristics of the women enrolled in the GENEPSO cohort and the survey, approximately one-third of BRCA1/2 mutation carriers were eligible for the trial. Five hundred and thirty-four women eligible from chart review have been informed by mail about the prevention trial and were invited to an oral information by participating centres. Forty-four percentage of them came to the dedicated medical visit. Uptake of drug prevention trial was 32% among women informed orally and 15% of all the eligible women. The main reasons of refusal were: potential side effects, probability to receive the placebo and lack of support from their physicians. Additionally, we noticed that prior prophylactic oophorectomy and previous unilateral breast cancer were more frequent in women enrolled in the LIBER trial than in the French cohort (93% vs. 60% and 50% vs. 39%, respectively). Based on an overall 15% uptake among all eligible subjects, greater and wider information of the trial should be offered to women with BRCA1/2 mutation to improve recruitment. Women with previous unilateral breast cancer or prior prophylactic oophorectomy are more likely to enter a medical prevention trial. PMID- 22076256 TI - Method of targeted delivery of laser beam to isolated retinal rods by fiber optics. AB - A method of controllable light delivery to retinal rod cells using an optical fiber is described. Photo-induced current of the living rod cells was measured with the suction electrode technique. The approach was tested with measurements relating the spatial distribution of the light intensity to photo-induced current. In addition, the ion current responses of rod cells to polarized light at two different orientation geometries of the cells were studied. PMID- 22076255 TI - CSF levels of oligomeric alpha-synuclein and beta-amyloid as biomarkers for neurodegenerative disease. AB - Protein misfolding and aggregation is a critically important feature in many devastating neurodegenerative diseases, therefore characterization of the CSF concentration profiles of selected key forms and morphologies of proteins involved in these diseases, including beta-amyloid (Abeta) and alpha-synuclein (a syn), can be an effective diagnostic assay for these diseases. CSF levels of tau and Abeta have been shown to have great promise as biomarkers for Alzheimer's disease. However since the onset and progression of many neurodegenerative diseases have been strongly correlated with the presence of soluble oligomeric aggregates of proteins including various Abeta and a-syn aggregate species, specific detection and quantification of levels of each of these different toxic protein species in CSF may provide a simple and accurate means to presymptomatically diagnose and distinguish between these diseases. Here we show that the presence of different protein morphologies in human CSF samples can be readily detected using highly selective morphology specific reagents in conjunction with a sensitive electronic biosensor. We further show that these morphology specific reagents can readily distinguish between post-mortem CSF samples from AD, PD and cognitively normal sources. These studies suggest that detection of specific oligomeric aggregate species holds great promise as sensitive biomarkers for neurodegenerative disease. PMID- 22076257 TI - Model of bleaching and acquisition for superresolution microscopy controlled by a single wavelength. AB - We consider acquisition schemes that maximize the fraction of images that contain only a single activated molecule (as opposed to multiple activated molecules) in superresolution localization microscopy of fluorescent probes. During a superresolution localization microscopy experiment, irreversible photobleaching destroys fluorescent molecules, limiting the ability to monitor the dynamics of long-lived processes. Here we consider experiments controlled by a single wavelength, so that the bleaching and activation rates are coupled variables. We use variational techniques and kinetic models to demonstrate that this coupling of bleaching and activation leads to very different optimal control schemes, depending on the detailed kinetics of fluorophore activation and bleaching. Likewise, we show that the robustness of the acquisition scheme is strongly dependent on the detailed kinetics of activation and bleaching. PMID- 22076258 TI - Femtosecond infrared intrastromal ablation and backscattering-mode adaptive optics multiphoton microscopy in chicken corneas. AB - The performance of femtosecond (fs) laser intrastromal ablation was evaluated with backscattering-mode adaptive-optics multiphoton microscopy in ex vivo chicken corneas. The pulse energy of the fs source used for ablation was set to generate two different ablation patterns within the corneal stroma at a certain depth. Intrastromal patterns were imaged with a custom adaptive-optics multiphoton microscope to determine the accuracy of the procedure and verify the outcomes. This study demonstrates the potential of using fs pulses as surgical and monitoring techniques to systematically investigate intratissue ablation. Further refinement of the experimental system by combining both functions into a single fs laser system would be the basis to establish new techniques capable of monitoring corneal surgery without labeling in real-time. Since the backscattering configuration has also been optimized, future in vivo implementations would also be of interest in clinical environments involving corneal ablation procedures. PMID- 22076259 TI - Double-clad fiber with a tapered end for confocal endomicroscopy. AB - We present a double-clad fiber coupler (DCFC) for use in confocal endomicroscopy to reduce speckle contrast, increase signal collection while preserving optical sectioning. The DCFC is made by incorporating a double-clad tapered fiber (DCTF) to a fused-tapered DCFC for achromatic transmission (from 1265 nm to 1325 nm) of > 95% illumination light trough the single mode (SM) core and collection of > 40% diffuse light through inner cladding modes. Its potential for confocal endomicroscopy is demonstrated in a spectrally-encoded imaging setup which shows a 3 times reduction in speckle contrast as well as 5.5 * increase in signal collection compared to imaging with a SM fiber. PMID- 22076260 TI - Photoacoustic section imaging with an integrating cylindrical detector. AB - A piezoelectric detector with a cylindrical shape is investigated for photoacoustic section imaging. Images are acquired by rotating a sample in front of the cylindrical detector. With its length exceeding the size of the imaging object, it works as an integrating sensor and therefore allows reconstructing section images with the inverse Radon transform. Prior to the reconstruction the Abel transform is applied to the measured signals to improve the accuracy of the image. A resolution of about 100 um within a section and of 500 um between sections is obtained. Additionally, a series of images of a zebra fish is shown. PMID- 22076261 TI - 3D imaging of biofilms on implants by detection of scattered light with a scanning laser optical tomograph. AB - Biofilms - communities of microorganisms attached to surfaces - are a constant threat for long-term success in modern implantology. The application of laser scanning microscopy (LSM) has increased the knowledge about microscopic properties of biofilms, whereas a 3D imaging technique for the large scale visualization of bacterial growth and migration on curved and non-transparent surfaces is not realized so far.Towards this goal, we built a scanning laser optical tomography (SLOT) setup detecting scattered laser light to image biofilm on dental implant surfaces. SLOT enables the visualization of living biofilms in 3D by detecting the wavelength-dependent absorption of non-fluorescent stains like e.g. reduced triphenyltetrazolium chloride (TTC) accumulated within metabolically active bacterial cells. Thus, the presented system allows the large scale investigation of vital biofilm structure and in vitro development on cylindrical and non-transparent objects without the need for fluorescent vital staining. We suggest SLOT to be a valuable tool for the structural and volumetric investigation of biofilm formation on implants with sizes up to several millimeters. PMID- 22076262 TI - Spectroscopic-speckle variance OCT for microvasculature detection and analysis. AB - We propose and studied optical coherence tomography (OCT) combining spectroscopic (SOCT) and speckle variance (svOCT) functions to effectively detect locations of microvasculatures and assess blood oxygen saturation level. Chorioallantoic membrane of a chick embryo was imaged in vivo to perform the analysis of the system. We also studied the effect of speckle in spectral domain using experimental data and performed time-averaging to reduce speckle noise locally. We combined SOCT and svOCT images using hue, saturation and value (HSV) color map to show the localized spectroscopic property of blood. Results show distinct spectroscopic properties between arterial blood and capillary blood. PMID- 22076263 TI - Photon efficient double-helix PSF microscopy with application to 3D photo activation localization imaging. AB - We present a double-helix point spread function (DH-PSF) based three-dimensional (3D) microscope with efficient photon collection using a phase mask fabricated by gray-level lithography. The system using the phase mask more than doubles the efficiency of current liquid crystal spatial light modulator implementations. We demonstrate the phase mask DH-PSF microscope for 3D photo-activation localization microscopy (PM-DH-PALM) over an extended axial range. PMID- 22076264 TI - Imaging workflow and calibration for CT-guided time-domain fluorescence tomography. AB - In this study, several key optimization steps are outlined for a non-contact, time-correlated single photon counting small animal optical tomography system, using simultaneous collection of both fluorescence and transmittance data. The system is presented for time-domain image reconstruction in vivo, illustrating the sensitivity from single photon counting and the calibration steps needed to accurately process the data. In particular, laser time- and amplitude referencing, detector and filter calibrations, and collection of a suitable instrument response function are all presented in the context of time-domain fluorescence tomography and a fully automated workflow is described. Preliminary phantom time-domain reconstructed images demonstrate the fidelity of the workflow for fluorescence tomography based on signal from multiple time gates. PMID- 22076265 TI - Micrometer axial resolution OCT for corneal imaging. AB - An optical coherence tomography (OCT) for high axial resolution corneal imaging is presented. The system uses 375 nm bandwidth (625 to 1000 nm) from a broadband supercontinuum light source. The system was developed in free space to minimize image quality degradation due to dispersion. A custom-designed spectrometer based on a Czerny Turner configuration was implemented to achieve an imaging depth of 1 mm. Experimentally measured axial resolution was 1.1 MUm in corneal tissue and had a good agreement with the theoretically calculated resolution from the envelope of the spectral interference fringes. In vivo imaging was carried out and thin corneal layers such as the tear film and the Bowman's layer were quantified in normal, keratoconus, and contact lens wearing eyes, indicating the system's suitability for several ophthalmic applications. PMID- 22076266 TI - Tissue oximetry: a comparison of mean values of regional tissue saturation, reproducibility and dynamic range of four NIRS-instruments on the human forearm. AB - We compared absolute values of regional tissue hemoglobin saturation (StO(2)), reproducibility, and dynamic range of four different instruments on the forearm of adults. The sensors were repositioned 10 times on each subject. Dynamic range was estimated by exercise with subsequent arterial occlusion. Mean StO(2) was 70.1% +/- 6.7 with INVOS 5100, 69.4% +/- 5.0 with NIRO 200 NX, 63.4% +/- 4.5 with NIRO 300, and 60.8% +/- 3.6 with OxyPrem. The corresponding reproducibility S(w) was 5.4% (CI 4.4-6.9), 4.4% (CI 3.5-5.2), 4.1% (CI 3.3-4.9), and 2.7% (CI 2.2 3.2), respectively. The dynamic ranges DeltaStO(2) were 45.0%, 46.8%, 44.8%, and 27.8%, respectively. In conclusion, the three commercial NIRS instruments showed different absolute values, whereas reproducibility and dynamic range were quite similar. PMID- 22076267 TI - Effects of probe geometry on transscleral diffuse optical spectroscopy. AB - The purpose of this study was to investigate how the geometry of a fiber optic probe affects the transmission and reflection of light through the scleral eye wall. Two geometrical parameters of the fiber probe were investigated: the source detector distance and the fiber protrusion, i.e. the length of the fiber extending from the flat surface of the fiber probe. For optimization of the fiber optic probe geometry, fluorescence stained choroidal tumor phantoms in ex vivo porcine eyes were measured with both diffuse reflectance- and laser-induced fluorescence spectroscopy. The strength of the fluorescence signal compared to the excitation signal was used as a measure for optimization. Intraocular pressure (IOP) and temperature were monitored to assess the impact of the probe on the eye. For visualizing any possible damage caused by the probe, the scleral surface was imaged with scanning electron microscopy after completion of the spectroscopic measurements. A source-detector distance of 5 mm with zero fiber protrusion was considered optimal in terms of spectroscopic contrast, however, a slight fiber protrusion of 0.5 mm is argued to be advantageous for clinical measurements. The study further indicates that transscleral spectroscopy can be safely performed in human eyes under in vivo conditions, without leading to an unacceptable IOP elevation, a significant rise in tissue temperature, or any visible damage to the scleral surface. PMID- 22076268 TI - Thermal intravascular photoacoustic imaging. AB - Intravascular photoacoustics (IVPA)-a minimally invasive imaging technique with contrast related to optical absorption properties of tissue, can be used to visualize atherosclerotic plaques. However, the amplitude of photoacoustic signals is also related to a temperature dependent, tissue specific parameter-the Gruneisen parameter. Therefore, photoacoustic signals measured at different temperatures may reveal information about tissue composition. In this study, thermal IVPA (tIVPA) imaging was introduced. The imaging studies were performed using an ex vivo atherosclerotic rabbit aorta. Temperature dependent photoacoustic responses from lipid in plaques and lipid in periadventitial tissue were different, thus allowing tIVPA images to delineate the location of lipid rich plaques. The results indicate that tIVPA imaging has a potential to characterize tissue composition in atherosclerotic vessels. PMID- 22076269 TI - Measurement of cerebral microvascular compliance in a model of atherosclerosis with optical coherence tomography. AB - Optical coherence tomography (OCT) has recently been used to produce 3D angiography of microvasculature and blood flow maps of large vessels in the rodent brain in-vivo. However, use of this optical method for the study of cerebrovascular disease has not been fully explored. Recent developments in neurodegenerative diseases has linked common cardiovascular risk factors to neurodegenerative risk factors hinting at a vascular hypothesis for the development of the latter. Tools for studying cerebral blood flow and the myogenic tone of cerebral vasculature have thus far been either highly invasive or required ex-vivo preparations therefore not preserving the delicate in-vivo conditions. We propose a novel technique for reconstructing the flow profile over a single cardiac cycle in order to evaluate flow pulsatility and vessel compliance. A vascular model is used to simulate changes in vascular compliance and interpret OCT results. Comparison between atherosclerotic and wild type mice show a trend towards increased compliance in the smaller arterioles of the brain (diameter < 80MUm) in the disease model. These results are consistent with previously published ex-vivo work confirming the ability of OCT to investigate vascular dysfunction. PMID- 22076270 TI - Novel non-contact retina camera for the rat and its application to dynamic retinal vessel analysis. AB - We present a novel non-invasive and non-contact system for reflex-free retinal imaging and dynamic retinal vessel analysis in the rat. Theoretical analysis was performed prior to development of the new optical design, taking into account the optical properties of the rat eye and its specific illumination and imaging requirements. A novel optical model of the rat eye was developed for use with standard optical design software, facilitating both sequential and non-sequential modes. A retinal camera for the rat was constructed using standard optical and mechanical components. The addition of a customized illumination unit and existing standard software enabled dynamic vessel analysis. Seven-minute in-vivo vessel diameter recordings performed on 9 Brown-Norway rats showed stable readings. On average, the coefficient of variation was (1.1 +/- 0.19) % for the arteries and (0.6 +/- 0.08) % for the veins. The slope of the linear regression analysis was (0.56 +/- 0.26) % for the arteries and (0.15 +/- 0.27) % for the veins. In conclusion, the device can be used in basic studies of retinal vessel behavior. PMID- 22076271 TI - In vivo microstructural and microvascular imaging of the human corneo-scleral limbus using optical coherence tomography. AB - The corneo-scleral limbus contains several biological components, which are important constituents for understanding, diagnosing and managing several ocular pathologies, such as glaucoma and corneal abnormalities. An anterior segment optical coherence tomography (AS-OCT) system integrated with optical microangiography (OMAG) is used in this study to non-invasively visualize the three-dimensional microstructural and microvascular properties of the limbal region. Advantages include first the ability to correct optical distortion of microstructural images enabling quantification of relationships in the anterior chamber angle. Second, microvascular images enable the visualization of the microcirculation in the limbal area without the use of exogenous contrast agents. Third, by combining the microstructural and microvascular information, the aqueous outflow pathway can be identified. The proposed AS-OCT can serve as a useful tool for ophthalmological research to determine normal and pathologic changes in the outflow system. As a clinical tool it has the potential to detect early aqueous outflow system abnormalities that lead to the pressure elevation in glaucoma. Recent surgical innovations and their implementations also rely on an assessment of outflow system structure and function, which can be revealed by AS OCT. PMID- 22076272 TI - Spectrally encoded fiber-based structured lighting probe for intraoperative 3D imaging. AB - Three dimensional quantification of organ shape and structure during minimally invasive surgery (MIS) could enhance precision by allowing the registration of multi-modal or pre-operative image data (US/MRI/CT) with the live optical image. Structured illumination is one technique to obtain 3D information through the projection of a known pattern onto the tissue, although currently these systems tend to be used only for macroscopic imaging or open procedures rather than in endoscopy. To account for occlusions, where a projected feature may be hidden from view and/or confused with a neighboring point, a flexible multispectral structured illumination probe has been developed that labels each projected point with a specific wavelength using a supercontinuum laser. When imaged by a standard endoscope camera they can then be segmented using their RGB values, and their 3D coordinates calculated after camera calibration. The probe itself is sufficiently small (1.7 mm diameter) to allow it to be used in the biopsy channel of commonly used medical endoscopes. Surgical robots could therefore also employ this technology to solve navigation and visualization problems in MIS, and help to develop advanced surgical procedures such as natural orifice translumenal endoscopic surgery. PMID- 22076273 TI - Swept source optical coherence tomography as a tool for real time visualization and localization of electrodes used in electrophysiological studies of brain in vivo. AB - In studies of in vivo extracellular recording, we usually penetrate electrodes almost blindly into the neural tissue, in order to detect the neural activity from an expected target location at a certain depth. After the recording, it is necessary for us to determine the position of the electrodes precisely. Generally, to identify the position of the electrode, one method is to examine the postmortem tissue sample at micron resolution. The other method is using MRI and it does not have enough resolution to resolve the neural structures. To solve such problems, we propose swept source optical coherence tomography (SS-OCT) as a tool to visualize the cross-sectional image of the neural target structure along with the penetrating electrode. We focused on a rodent olfactory bulb (OB) as the target. We succeeded in imaging both the OB layer structure and the penetrating electrode, simultaneously. The method has the advantage of detecting the electrode shape and the position in real time, in vivo. These results indicate the possibility of using SS-OCT as a powerful tool for guiding the electrode into the target tissue precisely in real time and localizing the electrode tip during electrophysiological recordings. PMID- 22076274 TI - Measurement and correction of in vivo sample aberrations employing a nonlinear guide-star in two-photon excited fluorescence microscopy. AB - We demonstrate that sample induced aberrations can be measured in a nonlinear microscope. This uses the fact that two-photon excited fluorescence naturally produces a localized point source inside the sample: the nonlinear guide-star (NL GS). The wavefront emitted from the NL-GS can then be recorded using a Shack Hartmann sensor. Compensation of the recorded sample aberrations is performed by the deformable mirror in a single-step. This technique is applied to fixed and in vivo biological samples, showing, in some cases, more than one order of magnitude improvement in the total collected signal intensity. PMID- 22076275 TI - Measurement of tissue scattering properties using multi-diameter single fiber reflectance spectroscopy: in silico sensitivity analysis. AB - Multiple diameter single fiber reflectance (MDSFR) measurements of turbid media can be used to determine the reduced scattering coefficient (MU'(s)) and a parameter that characterizes the phase function (gamma). The MDSFR method utilizes a semi-empirical model that expresses the collected single fiber reflectance intensity as a function of fiber diameter (d(fiber)), MU'(s), and gamma. This study investigated the sensitivity of the MDSFR estimates of MU'(s) and gamma to the choice of fiber diameters and spectral information incorporated into the fitting procedure. The fit algorithm was tested using Monte Carlo simulations of single fiber reflectance intensities that investigated biologically relevant ranges of scattering properties (MU'(s) ? [0.4 - 4]mm(-1)) and phase functions (gamma ? [1.4 - 1.9]) and for multiple fiber diameters (d(fiber) ? [0.2 - 1.5] mm). MDSFR analysis yielded accurate estimates of MU'(s) and gamma over the wide range of scattering combinations; parameter accuracy was shown to be sensitive to the range of fiber diameters included in the analysis, but not to the number of intermediate fibers. Moreover, accurate parameter estimates were obtained without a priori knowledge about the spectral shape of gamma. Observations were used to develop heuristic guidelines for the design of clinically applicable MDSFR probes. PMID- 22076276 TI - Fabrication of microscale medical devices by two-photon polymerization with multiple foci via a spatial light modulator. AB - Two-photon polymerization is an appealing technique for producing microscale devices due to its flexibility in producing structures with a wide range of geometries as well as its compatibility with materials suitable for biomedical applications. The greatest limiting factor in widespread use of two-photon polymerization is the slow fabrication times associated with line-by-line, high resolution structuring. In this study, a recently developed technology was used to produce microstructures by two-photon polymerization with multiple foci, which significantly reduces the production time. Computer generated hologram pattern technology was used to generate multiple laser beams in controlled positions from a single laser. These multiple beams were then used to simultaneously produce multiple microstructures by two-photon polymerization. Arrays of micro-Venus structures, tissue engineering scaffolds, and microneedle arrays were produced by multifocus two-photon polymerization. To our knowledge, this work is the first demonstration of multifocus two-photon polymerization technology for production of a functional medical device. Multibeam fabrication has the potential to greatly improve the efficiency of two-photon polymerization production of microscale devices such as tissue engineering scaffolds and microneedle arrays. PMID- 22076277 TI - Bioluminescence tomography using eigenvectors expansion and iterative solution for the optimized permissible source region. AB - A reconstruction algorithm for bioluminescence tomography (BLT) has been developed. The algorithm numerically calculates the Green's function at different wavelengths using the diffusion equation and finite element method. The optical properties used in calculating the Green's function are reconstructed using diffuse optical tomography (DOT) and assuming anatomical information is provided by x-ray computed tomography or other methods. A symmetric system of equations is formed using the Green's function and the measured light fluence rate and the resulting eigenvalue problem is solved to get the eigenvectors of this symmetric system of equations. A space can be formed from the eigenvectors obtained and the reconstructed source is written as an expansion of the eigenvectors corresponding to non-zero eigenvalues. The coefficients of the expansion are found to obtain the reconstructed BL source distribution. The problem is solved iteratively by using a permissible source region that is shrunk by removing nodes with low probability to contribute to the source. Throughout this process the permissible region shrinks from the entire object to just a few nodes. The best estimate of the reconstructed source is chosen that which minimizes the difference between the calculated and measured light fluence rates. 3D simulations presented here show that the reconstructed source is in good agreement with the actual source in terms of locations, magnitudes, sizes, and total powers for both localized multiple sources and large inhomogeneous source distributions. PMID- 22076278 TI - Tissue-mimicking phantoms for photoacoustic and ultrasonic imaging. AB - In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid((r)) 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies. PMID- 22076279 TI - High-performance image reconstruction in fluorescence tomography on desktop computers and graphics hardware. AB - Image reconstruction in fluorescence optical tomography is a three-dimensional nonlinear ill-posed problem governed by a system of partial differential equations. In this paper we demonstrate that a combination of state of the art numerical algorithms and a careful hardware optimized implementation allows to solve this large-scale inverse problem in a few seconds on standard desktop PCs with modern graphics hardware. In particular, we present methods to solve not only the forward but also the non-linear inverse problem by massively parallel programming on graphics processors. A comparison of optimized CPU and GPU implementations shows that the reconstruction can be accelerated by factors of about 15 through the use of the graphics hardware without compromising the accuracy in the reconstructed images. PMID- 22076280 TI - Light assisted antibody immobilization for bio-sensing. AB - Ultrashort UV pulses at 258 nm with repetition rate of 10 kHz have been used to irradiate buffer solution of antibody. The tryptophan residues strongly absorb this radiation thus becoming capable to disrupt the disulfide bridges located next to them. Due to their high reactivity the opened bridges can anchor a gold plate more efficiently than other sites of the macromolecule giving rise to preferential orientations of the variable part of the antibody. UV irradiation has been applied to anchor antiIgG antibody to the electrode of a Quartz Crystal Microbalance (QCM) that lends itself as a sensor, the antibody acting as the bio receptor. An increase of the QCM sensitivity and of the linear range has been measured when the antibody is irradiated with UV laser pulses. The photo-induced reactions leading to disulfide bridge breakage have been analyzed by means of a chemical assay that confirms our explanation. The control of disulfide bridges by UV light paves the way to important applications for sensing purpose since cysteine in combination with tryptophan can act as a hook to link refractory bio receptors to surfaces. PMID- 22076283 TI - Partial sensitization of human bladder cancer cells to a gene-therapeutic adenovirus carrying REIC/Dkk-3 by downregulation of BRPK/PINK1. AB - REIC/Dkk-3 is a tumor suppressor gene that was first identified as a gene downregulated in association with immortalization of normal human fibroblasts. We have demonstrated that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) showed a tumor specific killing effect on a wide range of cancers. However, some human cancers, bladder cancers in particular, are resistant to Ad-REIC. In this study, we investigated the combination effect of downregulation of BRPK/PINK1 (PINK1) and Ad-REIC on bladder cancer cells. Five bladder cancer cell lines among six cell lines examined were resistant to Ad-REIC. Among the cell lines, the resistance of two cell lines was probably due to low infection efficiency of the adenovirus. PINK1-specific siRNA remarkably downregulated Bcl-xL and TRAP1 proteins and upregulated BAX protein expression. Finally, downregulation of PINK1 partially sensitized the other three cell lines that were resistant to Ad-REIC. This sensitization was associated with increasing production of reactive oxygen species (ROS). These results indicate that PINK1 is one of the key molecules for the mitochondrial protection system and that PINK1 can be a new target molecule to sensitize bladder cancer cells that are resistant to Ad-REIC. PMID- 22076284 TI - Rapid synthesis of highly functionalised alpha-amino amides and medium ring lactones using multicomponent reactions of amino alcohols and isocyanides. AB - Four-component reactions between amino alcohols, aldehydes, isocyanides and thiols proceed rapidly under microwave or conventional heating at 60 degrees C in methanol. The reaction is successful with a wide range of components and gives access to potentially drug-like products containing amine, amide and thioether functionality in moderate to excellent yield. The reaction conditions are also applicable to the synthesis of a range of 8-10 membered medium ring lactones via three-component reactions of amino alcohols, isocyanides and acid-aldehydes. Incorporation of L-prolinol as the amino alcohol component in each case gives access to multicomponent products with moderate to high diastereoselectivity. PMID- 22076285 TI - Fecal occult blood testing when colonoscopy capacity is limited. AB - BACKGROUND: Fecal occult blood testing (FOBT) can be adapted to a limited colonoscopy capacity by narrowing the age range or extending the screening interval, by using a more specific test or hemoglobin cutoff level for referral to colonoscopy, and by restricting surveillance colonoscopy. Which of these options is most clinically effective and cost-effective has yet to be established. METHODS: We used the validated MISCAN-Colon microsimulation model to estimate the number of colonoscopies, costs, and health effects of different screening strategies using guaiac FOBT or fecal immunochemical test (FIT) at various hemoglobin cutoff levels between 50 and 200 ng hemoglobin per mL, different surveillance strategies, and various age ranges. We optimized the allocation of a limited number of colonoscopies on the basis of incremental cost effectiveness. RESULTS: When colonoscopy capacity was unlimited, the optimal screening strategy was to administer an annual FIT with a 50 ng/mL hemoglobin cutoff level in individuals aged 45-80 years and to offer colonoscopy surveillance to all individuals with adenomas. When colonoscopy capacity was decreasing, the optimal screening adaptation was to first increase the FIT hemoglobin cutoff value to 200 ng hemoglobin per mL and narrow the age range to 50-75 years, to restrict colonoscopy surveillance, and finally to further decrease the number of screening rounds. FIT screening was always more cost effective compared with guaiac FOBT. Doubling colonoscopy capacity increased the benefits of FIT screening up to 100%. CONCLUSIONS: FIT should be used at higher hemoglobin cutoff levels when colonoscopy capacity is limited compared with unlimited and is more effective in terms of health outcomes and cost compared with guaiac FOBT at all colonoscopy capacity levels. Increasing the colonoscopy capacity substantially increases the health benefits of FIT screening. PMID- 22076286 TI - Less is more: not "going the distance" and why. PMID- 22076288 TI - Near-infrared autofluorescence and indocyanine green angiography in central serous chorioretinopathy. AB - PURPOSE: To evaluate the diagnostic potential of near-infrared (NIR) autofluorescence (AF) in central serous chorioretinopathy (CSC) and to present a method to analyze NIR-AF findings quantitatively. PROCEDURES: NIR-AF images, indocyanine green (ICG) angiograms, blue-light autofluorescence (BL-AF) images and fluorescein angiograms were recorded with the use of a confocal scanning laser ophthalmoscope in 19 eyes of 17 patients with CSC. Gray-value ratios were calculated to compare the methods. RESULTS: Using NIR-AF, hypofluorescent spots were observed at the leakage site in 18 of 19 eyes (94.7%). The mean gray-value ratio (+/-SD) was 0.55 +/- 0.22 for the site of the leakage point with NIR-AF and 0.65 +/- 0.35 with BL-AF. ICG angiography showed a gray-value ratio of 2.37 +/- 2.07. Fluorescein angiography had the best contrast, with a gray-value ratio of 13.44 +/- 15.02. CONCLUSION: NIR-AF demonstrated CSC in 94.7% of the cases. NIR AF may be a noninvasive alternative to detect CSC. PMID- 22076289 TI - Beta-blocker therapy for hypertension. AB - Hypertension has been linked to many diseases, including coronary heart disease, myocardial infarction, renal failure, and stroke. Treatment involves lowering blood pressure (BP) and altering the sequelae. Medications such as beta-blockers reduce BP and prevent complications such as ventricular remodeling, endothelial impairment, and renal insufficiency. This article describes the pathophysiology of hypertension, complications, and theories of primary hypertension. Critical care nurses will learn about the pharmacodynamics and latest research on beta blocker therapy and critical decision making for patients taking these medications. PMID- 22076292 TI - Celecoxib. PMID- 22076293 TI - Acute ischemic stroke. AB - Acute ischemic stroke, also known as brain attack, is the third-leading cause of death and the leading cause of adult disability in the United States. However, early management of this emergency can improve patient outcomes. This article reviews the types of stroke, prevention, signs and symptoms, and management. Guidelines for assessment and emergency care for patients with acute ischemic stroke also are provided. PMID- 22076294 TI - How to respond to shock. AB - This article describes three common types of shock-hypovolemic, septic, and cardiogenic-and how to recognize and respond appropriately. Shock has many causes, but the underlying disease process is the same, and prompt, aggressive intervention is the key to improved patient outcomes. PMID- 22076295 TI - Nurses and informed consent, part 2. PMID- 22076296 TI - Six critical thinking skills for at-the-bedside success. PMID- 22076297 TI - Using variance tracking to improve outcomes and reduce costs. AB - Clinical pathways outline patient-care delivery over time for specific patient populations, but their true utility is derived from information obtained through variance tracking-documenting when and why a patient's care varies from the clinical pathway. This article describes one health care facility's variance tracking for pulmonary, medical oncology, and nephrology patients and their associated measured outcomes. Avoidable hospital days were tracked and a performance improvement initiative, focused on the pathways most often used on the medical unit, was undertaken, resulting in decreased length of patient stay and cost savings of more than $160,000. PMID- 22076299 TI - Comparing tympanic membrane and pulmonary artery catheter temperatures. AB - Studies comparing tympanic membrane thermometry with other thermometry methods have had conflicting results. Our hospital's nursing practice council sponsored this tympanic thermometry study in our cardiac surgical intensive care unit to assess the feasibility of increasing tympanic thermometer use in our hospital. Our results suggest clinically significant discrepancies between tympanic membrane and pulmonary artery catheter temperatures. These discrepancies preclude expanding tympanic thermometer use in our hospital. PMID- 22076300 TI - Finding a common ground. PMID- 22076302 TI - Characterizing the phylogenetic tree-search problem. AB - Phylogenetic trees are important in many areas of biological research, ranging from systematic studies to the methods used for genome annotation. Finding the best scoring tree under any optimality criterion is an NP-hard problem, which necessitates the use of heuristics for tree-search. Although tree-search plays a major role in obtaining a tree estimate, there remains a limited understanding of its characteristics and how the elements of the statistical inferential procedure interact with the algorithms used. This study begins to answer some of these questions through a detailed examination of maximum likelihood tree-search on a wide range of real genome-scale data sets. We examine all 10,395 trees for each of the 106 genes of an eight-taxa yeast phylogenomic data set, then apply different tree-search algorithms to investigate their performance. We extend our findings by examining two larger genome-scale data sets and a large disparate data set that has been previously used to benchmark the performance of tree search programs. We identify several broad trends occurring during tree-search that provide an insight into the performance of heuristics and may, in the future, aid their development. These trends include a tendency for the true maximum likelihood (best) tree to also be the shortest tree in terms of branch lengths, a weak tendency for tree-search to recover the best tree, and a tendency for tree-search to encounter fewer local optima in genes that have a high information content. When examining current heuristics for tree-search, we find that nearest-neighbor-interchange performs poorly, and frequently finds trees that are significantly different from the best tree. In contrast, subtree-pruning and-regrafting tends to perform well, nearly always finding trees that are not significantly different to the best tree. Finally, we demonstrate that the precise implementation of a tree-search strategy, including when and where parameters are optimized, can change the character of tree-search, and that good strategies for tree-search may combine existing tree-search programs. PMID- 22076303 TI - Ginsenoside-Rd potentiates apoptosis induced by hydrogen peroxide in basilar artery smooth muscle cells through the mitochondrial pathway. AB - Our previous studies showed that ginsenoside-Rd, a purified component from Panax notoginseng, inhibited cell proliferation and reversed basilar artery remodeling. The aim of this study was to investigate whether ginsenoside- Rd influences H(2)O(2)-induced apoptosis in basilar artery smooth muscle cells (BASMCs). The results showed that ginsenoside-Rd significantly potentiated H(2)O(2)-induced cell death and cell apoptosis. This resulted in a concentration-dependent reduction of the cell viability. Ginsenoside-Rd further increased cytochrome C release and caspase-9/caspase-3 activations, and reduced the stability of mitochondrial membrane potential (MMP) and the ratio of Bcl-2/Bax. Cyclosporine A, an inhibitor of mitochondrial-permeability transition, inhibited alteration of mitochondrial permeability induced by H(2)O(2) and reversed the effect of ginsenoside-Rd on MMP. Our data strongly suggest that ginsenoside-Rd potentiated H(2)O(2)-induced apoptosis of BASMCs through the mitochondria-dependent pathway. PMID- 22076304 TI - Pleomorphic adenoma gene-like 2 regulates expression of the p53 family member, p73, and induces cell cycle block and apoptosis in human promonocytic U937 cells. AB - The proto-oncogene, pleomorphic adenoma gene-like 2 (PLAGL2), is implicated in a variety of cancers including acute myeloid leukemia (AML), malignant glioma, colon cancer, and lung adenocarcinoma. There is additional evidence that PLAGL2 can function as a tumor suppressor by initiating cell cycle arrest and apoptosis. Interestingly, PLAGL2 has also been implicated in human myelodysplastic syndrome, a disease that is characterized by ineffective hematopoiesis and can lead to fatal cytopenias (low blood counts) as a result of increased apoptosis in the marrow, or, in about one-third of cases, can progress to AML. To gain a better understanding of the actions of PLAGL2 in human myeloid cells, we generated a stable PLAGL2-inducible cell line, using human promonocytic U937 cells. PLAGL2 expression inhibited cell proliferation which correlated with an accumulation of cells in G1, apoptotic DNA-laddering, an increase in caspase 3, 8, and 9 activity, and a loss of mitochondrial transmembrane potential. There was significant increase in the p53 homologue, p73, with PLAGL2 expression, and consistent with mechanisms of p73-regulated cell cycle control and apoptosis, there was increased expression of known p73 target genes p21, DR5, TRAIL, and Bax. PLAGL2-induced cell cycle block was abolished in the presence of p73 siRNA. Together, these data support a role for PLAGL2 in cell cycle regulation and apoptosis via activation of p73. PMID- 22076301 TI - Accuracy and precision of species trees: effects of locus, individual, and base pair sampling on inference of species trees in lizards of the Liolaemus darwinii group (Squamata, Liolaemidae). AB - Molecular phylogenetics has entered a new era in which species trees are estimated from a collection of gene trees using methods that accommodate their heterogeneity and discordance with the species tree. Empirical evaluation of species trees is necessary to assess the performance (i.e., accuracy and precision) of these methods with real data, which consists of gene genealogies likely shaped by different historical and demographic processes. We analyzed 20 loci for 16 species of the South American lizards of the Liolaemus darwinii species group and reconstructed a species tree with *BEAST, then compared the performance of this method under different sampling strategies of loci, individuals, and sequence lengths. We found an increase in the accuracy and precision of species trees with the number of loci, but for any number of loci, accuracy substantially decreased only when using only one individual per species or 25% of the full sequence length (~ 147 bp). In addition, locus "informativeness" was an important factor in the accuracy/precision of species trees when using a few loci, but it became increasingly irrelevant with additional loci. Our empirical results combined with the previous simulation studies suggest that there is an optimal range of sampling effort of loci, individuals, and sequence lengths for a given speciation history and information content of the data. Future studies should be directed toward further assessment of other factors that can impact performance of species trees, including gene flow, locus "informativeness," tree shape, missing data, and errors in species delimitation. PMID- 22076305 TI - Connectivity gradients between the default mode and attention control networks. AB - Functional imaging studies have shown reduced activity within the default mode network during attention-demanding tasks. The network circuitry underlying this suppression remains unclear. Proposed hypotheses include an attentional switch in the right anterior insula and reciprocal inhibition between the default mode and attention control networks. We analyzed resting state blood oxygen level dependent (BOLD) data from 1278 subjects from 26 sites and constructed whole brain maps of functional connectivity between 7266 regions of interest (ROIs) covering the gray matter at ~5 mm resolution. ROIs belonging to the default mode network and attention control network were identified based on correlation to six published seed locations. Spatial heterogeneity of correlation between the default mode and attention control networks was observed, with smoothly varying gradients in every hub of both networks that ranged smoothly from weakly but significantly anticorrelated to positively correlated. Such gradients were reproduced in 3 separate groups of subjects. Anticorrelated subregions were identified in major hubs of both networks. Between-network connectivity gradients strengthen with age during late adolescence and early adulthood, with associated sharpening of the boundaries of the default mode network, integration of the insula and cingulate with frontoparietal attentional regions, and decreasing correlation between the default mode and attention control networks with age. PMID- 22076306 TI - Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review). AB - In some inflammasomes tumor cells are generated. The internal environment of the inflammasome is conducive to the induction of malignant transformation. Epigenetic changes initiate this process. The subverted stromal connective tissue cells act to promote and sustain the process of malignant trans-formation. In its early stages, the premalignant cells depend on paracrine circuitries for the reception of growth factors. The ligands are derived from the connective tissue, and the receptors are expressed on the recipient premalignant cells. The initial events are not a direct attack on the proto-oncogenes, and thus it may be entirely reversible. Epigenetic processes of hypermethylation of the genes at the promoters of tumor suppressor genes (to silence them), and deacetylation of the histones aimed at the promoters of proto-oncogenes (to activate them) are on going. A large number of short RNA sequences (interfering, micro-, short hairpin, non-coding RNAs) silence tumor suppressor genes, by neutralizing their mRNAs. In a serial sequence oncogenes undergo amplifications, point-mutations, translocations and fusions. In its earliest stage, the process is reversible by demethylation of the silenced suppressor gene promoters (to reactivate them), or re-acetylation of the histones of the oncogene promoters, thus de-activating them. The external administration of histone deacetylase inhibitors usually leads to the restoration of histone acetylation. In time, the uncorrected processes solidify into constitutive and irreversible gene mutations. Some of the pathogens inducing inflammations with consquential malignant transformation contain oncogenic gene sequences (papilloma viruses, Epstein-Barr virus, Kaposi's sarcoma associated herpesvirus, hepatitis B and C viruses, Merkel cell polyoma virus, Helicobacter pylori, enterotoxigenic Bacteroides fragilis). These induced malignancies may be multifocal. Other pathogens are devoid of any known oncogenic genomic sequences (mycoplasma vav-carcinogenesis, chlamydia MALT-lymphoma genesis). In these cases the host's inflammatory reactions induce the malignant transformation in serial sequences of gene alterations initiated by hypoxia and reactive oxygen and nitrogen species generation. Carcinogenic intrinsic inflammatory processes endogenously initiated without a pathogen are recognized. Chronic inflammatory processes signal the RNA/DNA complex. In response, the DNA may revert into its ancient primordial 'immortal' format, which the clinics recognize as 'oncogenesis'. The DNA remains the ultimate master of bioengineering in order to sustain life. A discussion on the most versatile and resistant primordial RNA/DNA complex and the pre-, proto-, and unicellular world in which they co-existed is included. PMID- 22076307 TI - Characteristics of premenopausal and postmenopausal women with acquired, generalized hypoactive sexual desire disorder: the Hypoactive Sexual Desire Disorder Registry for women. AB - OBJECTIVE: Little is known about the natural history of hypoactive sexual desire disorder (HSDD). We examined the sociodemographic, relationship, help seeking, sexual function, and medical characteristics of women with a clinical diagnosis of generalized, acquired HSDD by menopause status. METHODS: This study was a cross-sectional baseline data analysis from the HSDD Registry for Women (N = 1,574, from 33 US clinical sites). HSDD was clinically diagnosed and confirmed. Validated measures of sexual function, relationship factors, and health, as well as newly developed questions on help seeking were assessed using the questionnaire. RESULTS: Participants were predominantly married or living with a partner (81.7%) and represented a range of race/ethnic backgrounds and ages (mean +/- SD, 42.9 +/- 11.9 y). Most (56.8%) described their HSDD severity as "moderate to severe," with 26.5% rating the problem severe. Nonetheless, most women (69.8%) reported being happy in their relationship, and 61.8% were satisfied with their partner communication. Postmenopausal women had lower Female Sexual Function Index total scores, indicating worse sexual function (14.0 +/- 7.5) than premenopausal women (16.7 +/- 6.8, P < 0.001), although both groups had similarly low scores on the sexual desire domain (3.4 +/- 1.3 vs 3.3 +/- 1.4). Less than half of the overall sample had sought professional help, among whom hormonal treatments had been used by 23.7% of postmenopausal women and by 7.6% of premenopausal women. CONCLUSIONS: Most women with HSDD were in long-term partner relationships with high levels of overall relationship satisfaction. Postmenopausal women were more likely to seek help for their disorder, despite similarly high levels of distress associated with HSDD. Further research is needed to examine treatment outcomes. PMID- 22076308 TI - Association of leisure physical activity and sleep with cardiovascular risk factors in postmenopausal women. AB - OBJECTIVE: The aim of this study was to examine the individual and combined associations of leisure-time physical activity and sleep with cardiovascular risk factors in postmenopausal women. METHODS: We analyzed 48-month cross-sectional follow-up data from 393 participants of the Women on the Move Through Activity and Nutrition Study, a behavioral weight loss trial. Leisure-time physical activity data were collected with the past-year Modifiable Activity Questionnaire, whereas sleep data were collected with the Pittsburgh Sleep Quality Index. We compared physical activity and sleep categories using analysis of variance, post hoc Scheffe tests, and multivariate analyses based on groups above/below the median leisure-time physical activity level, above/below the sleep quality value of 5, and above/below the sleep duration of 7 hours/day. RESULTS: The average sleep quality and sleep duration did not significantly differ between women with high and women with low physical activity levels. When women with good sleep quality were compared, higher physical activity levels were associated with lower body mass index (2.0 kg/m; 25, 75 quartiles, 0.3, 3.6), waist circumference (6.3 cm; 1.7, 10.9), and total body fat (2.1%; 0.3, 4.0; P < 0.05). When participants with poor sleep quality were compared, highly active women had lower trunk fat, total body fat, and insulin levels than less active women did (P < 0.05). In multivariate analysis, physical activity was significantly associated with high-density lipoprotein level, trunk fat, and total body fat after controlling for sleep quality, sleep duration, age, hormone therapy and smoking status, and body mass index. CONCLUSIONS: The combined associations of leisure-time physical activity and sleep suggest that cardiovascular risk factors are more favorable in highly active women relative to less active women regardless of sleep. PMID- 22076309 TI - Neuroprotection of desferrioxamine in lipopolysaccharide-induced nigrostriatal dopamine neuron degeneration. AB - Inflammation and iron accumulation in the substantia nigra (SN) are implicated in the pathogenesis of Parkinson's disease (PD). However, the relationship between neuroinflammation and iron mismanagement remain largely unknown. In the present study, an animal model induced by lipopolysaccharide (LPS) was used to evaluate iron concentration in the ventral midbrain with or without neuroinflammation. Furthermore, the iron chelator desferrioxamine (DFO) was used to explore its neuroprotective property against LPS-induced nigrostriatal degeneration. Adult C57BL/6 mice were treated with DFO (2.5 ug) commenced 3 days prior to or following microinjection of LPS into the striatum. Animal behavioral tests, as well as pathological and biochemical assays were performed to evaluate the nigrostriatal dopamine neuron degeneration and neuroprotective effects of DFO. Here, we report that the iron concentration in the ventral midbrain significantly increased following intrastriatal injection of LPS, and administration of DFO improved behavior deficits, attenuated dopamine (DA) neuron loss and striatal DA reduction, and alleviated microglial activation in the SN. These results suggest that DFO may possess neuroprotective effect against LPS-induced nigrostriatal dopamine neuron degeneration. PMID- 22076310 TI - The autotrophic contribution to soil respiration in a northern temperate deciduous forest and its response to stand disturbance. AB - The goal of this study was to evaluate the contribution of oak trees (Quercus spp.) and their associated mycorrhizal fungi to total community soil respiration in a deciduous forest (Black Rock Forest) and to explore the partitioning of autotrophic and heterotrophic respiration. Trees on twelve 75 * 75-m plots were girdled according to four treatments: girdling all the oaks on the plot (OG), girdling half of the oak trees on a plot (O50), girdling all non-oaks on a plot (NO), and a control (C). In addition, one circular plot (diameter 50 m) was created where all trees were girdled (ALL). Soil respiration was measured before and after tree girdling. A conservative estimate of the total autotrophic contribution is approximately 50%, as indicated by results on the ALL and OG plots. Rapid declines in carbon dioxide (CO(2)) flux from both the ALL and OG plots, 37 and 33%, respectively, were observed within 2 weeks following the treatment, demonstrating a fast turnover of recently fixed carbon. Responses from the NO and O50 treatments were statistically similar to the control. A non proportional decline in respiration rates along the gradient of change in live aboveground biomass complicated partitioning of the overall rate of soil respiration and indicates that belowground carbon flux is not linearly related to aboveground disturbance. Our findings suggest that in this system there is a threshold disturbance level between 35 and 74% of live aboveground biomass loss, beyond which belowground dynamics change dramatically. PMID- 22076311 TI - Wasting disease regulates long-term population dynamics in a threatened seagrass. AB - The role of disease in the long-term dynamics of threatened species is poorly quantified, as well as being under-represented in ecology and conservation management. To understand persistent host-pathogen interaction operating in a vulnerable habitat, we quantified dynamics driving patterns of seagrass density using a longitudinal study in a relatively pristine site (Isles of Scilly, UK). Replicated samples of eelgrass (Zostera marina) density and wasting disease prevalence, presumably caused by Labyrinthula zosterae, were taken from five meadows at the height of the growing season, over the years 1997-2010. Data were used to parameterise a population dynamic model, incorporating density-dependent factors and sea temperature records. We found that direct density and disease mediated feedback operate within a network of local populations. Furthermore, our results indicate that the strength of limitation to seagrass growth by disease was increased at higher temperatures. This modification of the coupled host pathogen dynamics forms a novel hypothesis to account for dramatic die-backs of Z. marina widely reported elsewhere. Our findings highlight the importance of disease in structuring distributions of vulnerable species, as well as the application of population modelling in order to reveal ecological processes and prioritize future mechanistic investigation. PMID- 22076312 TI - Development of a bar adsorptive micro-extraction-large-volume injection-gas chromatography-mass spectrometric method for pharmaceuticals and personal care products in environmental water matrices. AB - The combination of bar adsorptive micro-extraction using activated carbon (AC) and polystyrene-divinylbenzene copolymer (PS-DVB) sorbent phases, followed by liquid desorption and large-volume injection gas chromatography coupled to mass spectrometry, under selected ion monitoring mode acquisition, was developed for the first time to monitor pharmaceutical and personal care products (PPCPs) in environmental water matrices. Assays performed on 25 mL water samples spiked (100 ng L(-1)) with caffeine, gemfibrozil, triclosan, propranolol, carbamazepine and diazepam, selected as model compounds, yielded recoveries ranging from 74% to 99% under optimised experimental conditions (equilibrium time, 16 h (1,000 rpm); matrix characteristics: pH 5, 5% NaCl for AC phase; LD: methanol/acetonitrile (1:1), 45 min). The analytical performance showed good precision (RSD < 18%), convenient detection limits (5-20 ng L(-1)) and excellent linear dynamic range (20-800 ng L(-1)) with remarkable determination coefficients (r(2) > 0.99), where the PS-DVB sorbent phase showed a much better efficiency. By using the standard addition methodology, the application of the present analytical approach on tap, ground, sea, estuary and wastewater samples allowed very good performance at the trace level. The proposed method proved to be a suitable sorption-based micro extraction alternative for the analysis of priority pollutants with medium-polar to polar characteristics, showing to be easy to implement, reliable, sensitive and requiring a low sample volume to monitor PPCPs in water matrices. PMID- 22076313 TI - Catecholamine analysis with strong cation exchange column liquid chromatography peroxyoxalate chemiluminescence reaction detection. AB - A liquid chromatography-chemiluminescence detection method was developed and validated for the determination of catecholamines (norepinephrine, epinephrine, and dopamine) in mouse brains. Chromatography was performed on a strong cation exchange column (150 * 2.0-mm id) using an isocratic mobile phase of 65 mM potassium acetate/75 mM potassium phosphate (95:5, pH 3.5) at a flow rate of 0.2 mL/min following post-column fluorescence derivatization of catecholamines with ethylenediamine and peroxyoxalate chemiluminescence reaction detection. The recovery of catecholamines added to mouse brain samples was more than 95.0%, while intra- and inter-day precision of the assay were <4.8%. The validated method was used to determine norepinephrine and dopamine concentrations in mouse brains without prior sample purification. PMID- 22076314 TI - Racial and ethnic disparities in the continuation of community-based children's mental health services. AB - This paper examines racial and ethnic disparities in continuation of mental health services for children and youth in California and how English language proficiency moderates the effect of race/ethnicity on the continuation of service. While previous research indicated racial/ethnic or geographic disparities in accessing mental health services among children and youth, few studies specifically focused on the continuation of mental health care. The authors used administrative data from California county mental health services users under age 25. Applying logistic regression, English language proficiency was found to be the major determinant of continuation of mental health services in this age group. With the exception of children of Asian descent, non-English speaking children and youth of diverse racial/ethnic background were significantly less likely to continue receiving mental health services compared with White English-speaking peers, even after controlling for sociodemographic, clinical and county characteristics. PMID- 22076315 TI - Discrepancy in diagnosis and treatment of post-traumatic stress disorder (PTSD): treatment for the wrong reason. AB - In primary care (PC), patients with post-traumatic stress disorder (PTSD) are often undiagnosed. To determine variables associated with treatment, this cross sectional study assessed 592 adult patients for PTSD. Electronic medical record (EMR) review of the prior 12 months assessed mental health (MH) diagnoses and MH treatments [selective serotonin reuptake inhibitor (SSRI) and/or >=1 visit with MH professional]. Of 133 adults with PTSD, half (49%; 66/133) received an SSRI (18%), a visit with MH professional (14%), or both (17%). Of those treated, 88% (58/66) had an EMR MH diagnosis, the majority (71%; 47/66) depression and (18%; 12/66) PTSD. The odds of receiving MH treatment were increased 8.2 times (95% CI 3.1-21.5) for patients with an EMR MH diagnosis. Nearly 50% of patients with PTSD received MH treatment, yet few had this diagnosis documented. Treatment was likely due to overlap in the management of PTSD and other mental illnesses. PMID- 22076316 TI - Adult cerebellar glioblastoma cases have different characteristics from supratentorial glioblastoma. AB - This study is a histological and clinical investigation of four cases of cerebellar glioblastoma, a rare tumor. The cases included three males and one female, from 33 to 67 years in age (mean 49 years). Tumor resection, postoperative irradiation and chemotherapy were performed in all cases. Two patients died of local tumor recurrence after 14 and 27 months. Another patient relapsed after 10 months; however, after additional tumor resection and second line chemotherapy, she remains disease-free 41 months after the initial treatment. The fourth patient has not relapsed in the 6 months since initial treatment. The histopathology of all cases was glioblastoma with pseudopalisading necrosis. However, low-grade glioma histopathology was found in three patients. All glioblastomas were immunopositive for p53 and immunonegative for epidermal growth factor receptor (EGFR) and isocitrate dehydrogenase 1 (IDH1). These adult cerebellar glioblastoma cases had similar clinical and pathological characteristics, and had different characteristics compared with supratentorial glioblastomas. PMID- 22076318 TI - Expression of ERalpha, its ERalphaDelta3 Splice Variant and gamma-SYNUCLEIN in Ovarian Cancer: A Pilot Study. AB - AIMS: Ovarian cancer has the highest mortality of any gynaecological malignancy; this is due to rapid peritoneal spread of tumour cells and neovascularization. Understanding the mechanisms underlying this is critical to developing early diagnostic or treatment strategies. We devised a pilot study to examine the role of gamma-SYNUCLEIN (gamma-SYN), oestrogen receptor (ER)alpha, and the splice variant ERalphaDelta3. METHODOLOGY: With ethical approval, ovarian tissue was collected from patients (n=24) undergoing oopherectomy for non-ovarian pathology or primary surgery for suspected ovarian cancer. Quantitative gene expression analysis was employed for gamma-SYN, ERalpha, and ERalphaDelta3. To identify the in situ localization, immunofluorescence for gamma-syn was carried out. RESULTS: Ovarian tumour tissue exhibited an elevated expression of gamma-SYN and high grade tumours had an elevated ERalphaDelta3:ERalpha ratio compared with benign tissue. The majority of previous studies point to the gamma-syn protein being present in epithelial cells of high-grade disease. Our study supports this, but additionally we conclusively identify its presence in the endothelial cells of vasculature surrounding low-grade disease; immunofluorescence was strongest in the apical cells surrounding the lumen. CONCLUSION: Our results demonstrate for the first time that there are readily-expressed levels of gamma-SYN and ERalphaDelta3 in normal ovarian tissue and ovarian tumours. In high-grade disease, gamma-syn and an elevated ERalphaDelta3:ERalpha ratio might confer metastatic potential to the tumourigenic cells and promote neoangiogenesis. Future in vitro studies might be necessary to delineate such a mechanism, which could potentially be the basis of early intervention. PMID- 22076317 TI - The added value of quantitative multi-voxel MR spectroscopy in breast magnetic resonance imaging. AB - OBJECTIVE: To determine whether quantitative multivoxel MRS improves the accuracy of MRI in the assessment of breast lesions. METHODS: Twenty-five consecutive patients with 26 breast lesions >= 1 cm assessed as BI-RADS 3 or 4 with mammography underwent quantitative multivoxel MRS and contrast-enhanced MRI. The choline (Cho) concentration was calculated using the unsuppressed water signal as a concentration reference. ROC analysis established the diagnostic accuracy of MRI and MRS in the assessment of breast lesions. RESULTS: Respective Cho concentrations in 26 breast lesions re-classified by MRI as BI-RADS 2 (n = 5), 3 (n = 8), 4 (n = 5) and 5 (n = 8) were 1.16 +/- 0.43 (mean +/- SD), 1.43 +/- 0.47, 2.98 +/- 2.15 and 4.94 +/- 3.10 mM. Two BI-RADS 3 lesions and all BI-RADS 4 and 5 lesions were malignant on histopathology and had Cho concentrations between 1.7 and 11.8 mM (4.03 +/- 2.72 SD), which were significantly higher (P = 0.01) than that in the 11 benign lesions (0.4-1.5 mM; 1.19 +/- 0.33 SD). Furthermore, Cho concentrations in the benign and malignant breast lesions in BI-RADS 3 category differed (P = 0.01). The accuracy of combined multivoxel MRS/breast MRI BI-RADS re-classification (AUC = 1.00) exceeded that of MRI alone (AUC = 0.96 +/- 0.03). CONCLUSIONS: These preliminary data indicate that multivoxel MRS improves the accuracy of MRI when using a Cho concentration cut-off <= 1.5 mM for benign lesions. KEY POINTS: Quantitative multivoxel MR spectroscopy can improve the accuracy of contrast-enhanced breast MRI. Multivoxel-MRS can differentiate breast lesions by using the highest Cho-concentration. Multivoxel-MRS can exclude patients with benign breast lesions from further invasive diagnostic procedures. PMID- 22076319 TI - Beyond the drive to satisfy needs: in the context of health care. AB - In the context of health care the aim of the article is to bring another meaning to the concept "need" that goes beyond the human activity; the drive to satisfy needs. Another meaning incorporates an ethical and existential nature of life phenomena. An example from empirical research on living with a chronic disease as seen from the patient's point of view provides the basis for arguing another meaning of the concept "need". The meanings and nuances in the life phenomena of hope, doubt and life courage are exemplified in qualitative interviews with chronic sufferers. A combination of empirical research and Danish life philosophy. Research has shown that the interaction between the professional health care provider and the patient and family may lead to a more or less unconscious and inappropriate administration of power. Research also indicates that by overlooking or ignoring the existential qualities in human life and suffering, the professional health care provider may deprive the patient and family of their room for action. To add a deeper understanding of the existential meaning of being a person with an illness, the article shows the different human dimensions concerning life phenomena and needs. Developing sensitive, situation specific attention offers a response to the challenge faced by health care providers in collaboration with the patient: How can we open our eyes to the most significant features of the situation which arise on the onset of illness. PMID- 22076320 TI - Pathophysiology of rosacea: introduction. PMID- 22076322 TI - Rosacea as a disease of cathelicidins and skin innate immunity. AB - Rosacea is a common and chronic inflammatory skin disease most frequently seen in groups of genetically related individuals. Although the symptoms of rosacea are heterogeneous, they are all related by the presence of characteristic facial or ocular inflammation involving both the vascular and tissue stroma. Until recently, the pathophysiology of this disease was limited to descriptions of a wide variety of factors that exacerbate or improve disease. Recent molecular studies show a common link between the triggers of rosacea and the cellular response, and these observations suggest that an altered innate immune response is involved in disease pathogenesis. Understanding rosacea as a disorder of innate immunity explains the benefits of current treatments and suggests new therapeutic strategies for alleviating this disease. PMID- 22076321 TI - Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. AB - Rosacea is a chronic inflammatory skin disease of unknown etiology. Although described centuries ago, the pathophysiology of this disease is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been identified yet. Four subtypes and several variants of rosacea have been described. It is still unclear whether these subtypes represent a "developmental march" of different stages or are merely part of a syndrome that develops independently but overlaps clinically. Clinical and histopathological characteristics of rosacea make it a fascinating "human disease model" for learning about the connection between the cutaneous vascular, nervous, and immune systems. Innate immune mechanisms and dysregulation of the neurovascular system are involved in rosacea initiation and perpetuation, although the complex network of primary induction and secondary reaction of neuroimmune communication is still unclear. Later, rosacea may result in fibrotic facial changes, suggesting a strong connection between chronic inflammatory processes and skin fibrosis development. This review highlights recent molecular (gene array) and cellular findings and aims to integrate the different body defense mechanisms into a modern concept of rosacea pathophysiology. PMID- 22076323 TI - Epidermal proteases in the pathogenesis of rosacea. AB - A number of different proteases and their inhibitors have a role in skin physiology and in the pathophysiology of inflammatory skin diseases. Proteases are important in the desquamation process and orderly regulation of the skin's barrier function. On the basis of the catalytic domain, proteases are classified into aspartate-, cysteine-, glutamate-, metallo-, serine-, and threonine proteases. Particularly, serine proteases (SPs) contribute to epidermal permeability barrier homeostasis, as acute barrier disruption increases SP activity in skin and inhibition by topical SP inhibitors accelerated recovery of barrier function after acute abrogation. In rosacea, increased levels of the vasoactive and inflammatory host-defense peptide cathelicidin LL-37 and its proteolytic peptide fragments were found, which were explained by an abnormal production of tryptic activity originating from kallikrein-related peptidase (KLK) 5. It is therefore possible that also other proteases, even from microbial or parasite origin, have a role in rosacea by forming alternate angiogenic and proinflammatory cathelicidin peptides. Further, the regulation of protease activity, in particular KLK-5 activity, might have a role in rosacea. This review briefly summarizes our current knowledge about keratinocyte-derived proteases and protease inhibitors, which might have a role in the pathophysiology of rosacea. PMID- 22076324 TI - The cutaneous vascular system in chronic skin inflammation. AB - The blood and lymphatic vasculature have an important role in skin homeostasis. Angiogenesis and lymphangiogenesis-the growth of new vessels from existing ones have received tremendous interest because of their role in promoting cancer spread. However, there is increasing evidence that both vessel types also have a major role in acute and chronic inflammatory disorders. Vessels change their phenotype during inflammation (vascular remodeling). In inflamed skin, vascular remodeling consists of a hyperpermeable, enlarged network of vessels with increased blood flow, and influx of inflammatory cells. During chronic inflammation, the activated endothelium expresses adhesion molecules, cytokines, and other molecules that lead to leukocyte rolling, attachment, and migration into the skin. Recent studies reveal that inhibition of blood vessel activation exerts potent anti-inflammatory properties. Thus, anti-angiogenic drugs might be used to treat inflammatory conditions. In particular, topical application of anti angiogenic drugs might be ideally suited to circumvent the adverse effects of systemic therapy with angiogenesis inhibitors. Our recent results indicate that stimulation of lymphatic vessel growth and function unexpectedly represents a new approach for treating chronic inflammatory disorders. PMID- 22076325 TI - Neurovascular aspects of skin neurogenic inflammation. AB - Neurogenic inflammation is involved in skin inflammation. It is hypothesized that it is involved in the pathogenesis of the common chronic cutaneous vascular disorder rosacea, but the exact mechanism of action is currently unknown. Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) are widely expressed on primary sensory neuron endings and non-neuronal cells such as keratinocytes. Here we describe the potential for TRPV1 and TRPA1 receptors to be involved in the pathophysiology of rosacea due to their polymodal activation, including cold and hot temperature, pungent products from vegetable and spices, reactive oxygen species, and mechanical stimuli. We discuss the role of both receptors and the sensory neuropeptides that they release in inflammation and pain sensation and evidence suggesting that both TRPV1 and TRPA1 receptors may be promising therapeutic targets for the treatment of the inflammatory symptoms of rosacea. PMID- 22076327 TI - The role of chronic inflammation in cutaneous fibrosis: fibroblast growth factor receptor deficiency in keratinocytes as an example. AB - Fibrosis is associated with a variety of skin diseases and causes severe aesthetic and functional impairments. Functional studies in rodents, together with clinical observations, strongly suggest a crucial role of chronic injury and inflammation in the pathogenesis of fibrotic diseases. The phenotype of mice lacking fibroblast growth factor (FGF) receptors 1 and 2 in keratinocytes supports this concept. In these mice, a defect in keratinocytes alone initiated an inflammatory response, which in turn caused keratinocyte hyperproliferation and dermal fibrosis. As the mechanism underlying this phenotype, we identified a loss of FGF-induced expression of claudins and occludin, which caused abnormalities in tight junctions with concomitant deficits in epidermal barrier function. This resulted in severe transepidermal water loss and skin dryness. In turn, activation of keratinocytes and epidermal gammadelta T cells occurred, which produced IL-1 family member 8 and S100A8 and S100A9. These cytokines attracted immune cells and activated fibroblasts, resulting in a double paracrine loop through production of keratinocyte mitogens by dermal cells. In addition, a profibrotic response was induced in fibroblasts. Our results highlight the importance of an intact epidermal barrier for the prevention of inflammation and fibrosis and the role of chronic inflammation in the pathogenesis of fibrotic diseases. PMID- 22076326 TI - Rosacea: The cytokine and chemokine network. AB - Rosacea is one of the most common dermatoses of adults. Recent studies have improved our understanding of the pathophysiology of rosacea. Current concepts suggest that known clinical trigger factors of rosacea such as UV radiation, heat, cold, stress, spicy food, and microbes modulate Toll-like receptor signaling, induce reactive oxygen species, as well as enhance antimicrobial peptide and neuropeptide production. Downstream of these events cytokines and chemokines orchestrate an inflammatory response that leads to the recruitment and activation of distinct leukocyte subsets and induces the characteristic histopathological features of rosacea. Here we summarize the current knowledge of the cytokine and chemokine network in rosacea and propose pathways that may be of therapeutic interest. PMID- 22076328 TI - Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. AB - Rosacea is a common skin disease with a high impact on quality of life. Characterized by erythema, edema, burning pain, immune infiltration, and facial skin fibrosis, rosacea has all the characteristics of neurogenic inflammation, a condition induced by sensory nerves via antidromically released neuromediators. To investigate the hypothesis of a central role of neural interactions in the pathophysiology, we analyzed molecular and morphological characteristics in the different subtypes of rosacea by immunohistochemistry, double immunofluorescence, morphometry, real-time PCR, and gene array analysis, and compared the findings with those for lupus erythematosus or healthy skin. Our results showed significantly dilated blood and lymphatic vessels. Signs of angiogenesis were only evident in phymatous rosacea. The number of mast cells and fibroblasts was increased in rosacea, already in subtypes in which fibrosis is not clinically apparent, indicating early activation. Sensory nerves were closely associated with blood vessels and mast cells, and were increased in erythematous rosacea. Gene array studies and qRT-PCR confirmed upregulation of genes involved in vasoregulation and neurogenic inflammation. Thus, dysregulation of mediators and receptors implicated in neurovascular and neuroimmune communication may be crucial at early stages of rosacea. Drugs that function on neurovascular and/or neuroimmune communication may be beneficial for the treatment of rosacea. PMID- 22076329 TI - Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates. AB - The controlled assembly and organization of multi-cellular systems to mimic complex tissue structures is critical to the engineering of tissues for therapeutic and diagnostic applications. Recent advances in micro-scale technologies to control multi-cellular aggregate formation typically require chemical modification of the interface between cells and materials and lack multi scale flexibility. Here we demonstrate that simple physical entrapment of magnetic microparticles within the extracellular space of stem cells spheroids during initial formation enables scaffold-free immobilization, translocation and directed assembly of multi-cellular aggregates across multiple length and time scales, even under dynamic suspension culture conditions. The response of aggregates to externally applied magnetic fields was a direct function of microparticle incorporation, allowing for rapid and transient control of the extracellular environment as well as separation of heterogeneous populations. In addition, spatial patterning of heterogeneous spheroid populations as well as individual multi-cellular aggregates was readily achieved by imposing temporary magnetic fields. Overall, this approach provides novel routes to examine stem cell differentiation and tissue morphogenesis with applications that encompass the creation of new model systems for developmental biology, scaffold-free tissue engineering strategies and scalable bioprocessing technologies. PMID- 22076330 TI - Enhanced mitophagy in Sertoli cells of ethanol-treated rats: morphological evidence and clinical relevance. AB - Although chronic ethanol consumption results in Sertoli cell vacuolization and augmented testicular germ cell apoptosis via death receptor and mitochondrial pathways, Sertoli cells are resistant to apoptosis. The aim of this study was to examine whether the activation of autophagy in the Sertoli cells of ethanol treated rats (ETR) may have a role in their survival. Adult Wistar rats were fed either 5% ethanol in Lieber-DeCarli liquid diet or an isocaloric control diet for 12 weeks. The TUNEL method demonstrated that Sertoli cells were always TUNEL negative despite the presence of many apoptotic germ cells in ETR, supporting our previous studies. Electron microscopy revealed the presence of large numbers of autophagic vacuoles (AVs) in Sertoli cells of ETR compared to few AVs in control testes. Most of the AVs in Sertoli cells of ETR enveloped and sequestered damaged and abnormally shaped mitochondria, without cytoplasm, indicating mitochondrial autophagy (mitophagy). Immuno-electron microscopy showed the localization of LC3, a specific marker of early AVs (autophagosomes), around AVs sequestering mitochondria in Sertoli cells of ETR. Immunohistochemical staining of LC3 demonstrated a punctate pattern in Sertoli cells of ETR, confirming the formation of autophagosomes, while LC3 puncta were almost absent in control testes. Moreover, increased immunoreactivity of LAMP-2, a lysosomal membrane protein and marker of late AVs (autolysosomes), was mainly observed in Sertoli cells of ETR, with weaker expression in control testes. Via the deletion of pro-apoptotic damaged mitochondria, enhanced Sertoli cell mitophagy in ETR may be an anti apoptotic mechanism that is essential for spermatogenesis. PMID- 22076331 TI - Sensitive electrochemical detection of the hydroxyl radical using enzyme catalyzed redox cycling. AB - Enzyme-catalyzed signal amplification was introduced to the electrochemical detection of the OH radical. In the presence of phenol as a trapping agent, glucose as a substrate, and pyrroloquinoline quinone-containing glucose dehydrogenase (PQQ-GDH) as a catalyst, the current signal for the trapping adducts (catechol and hydroquinone) produced by the hydroxylation of phenol could be amplified and detected sensitively. The limit of detection (S/N = 3) for catechol was 8 nM. The trapping efficiency of phenol was also estimated. PMID- 22076332 TI - Sequential injection immunoassay for environmental measurements. AB - Sequential injection immunoassay systems for environmental measurements based on the selective immunoreaction between antigen and antibody were described. A sequential injection analysis (SIA) technique is suitable to be applied for the procedure of enzyme-linked immunosorbent assay (ELISA), because the washing and the addition of reagent solutions can be automated by using a computer-controlled syringe pump and switching valve. We selected vitellogenin (Vg), which is a biomarker for evaluating environmental risk caused by endocrine-disrupting chemicals in the hydrosphere, and linear alkylbenzene sulfonates (LAS) and alkylphenol polyethoxylates (APEO), which are versatile surfactants, as target analytes in the flow immunoassay systems. For Vg monitoring, SIA systems based on spectrophotometric, chemiluminescence, and electrochemical determinations were constructed. On the other hand, chemiluminescence determination was applied to the detection of LAS and APEO. For APEO, an SIA system combined with surface plasmon resonance (SPR) sensor was also developed. These new sequential injection immunoassay systems are expected to be useful systems for environmental analysis. PMID- 22076333 TI - UV Raman markers for structural analysis of aromatic side chains in proteins. AB - UV Raman spectroscopy is a powerful tool for investigating the structures and interactions of the aromatic side chains of Phe, Tyr, Trp, and His in proteins. This is because Raman bands of aromatic ring vibrations are selectively enhanced with UV excitation, and intensities and wavenumbers of Raman bands sensitively reflect structures and interactions. Interpretation of protein Raman spectra is greatly assisted by using empirical correlations between spectra and structure. Many Raman bands of aromatic side chains have been proposed to be useful as markers of structures and interactions on the basis of empirical correlations. This article reviews the usefulness and limitations of the Raman markers for protonation/deprotonation, conformation, metal coordination, environmental polarity, hydrogen bonding, hydrophobic interaction, and cation-pi interaction of the aromatic side chains. The utility of Raman markers is demonstrated through an application to the structural analysis of a membrane-bound proton channel protein. PMID- 22076334 TI - Development of a simple vent-free interface for capillary gas chromatography-mass spectrometry. AB - A novel and simple interface for capillary gas chromatography-mass spectrometry (GC-MS) was developed using a piece of deactivated stainless-steel tubing. This interface eliminated the need to vent the MS ion source when changing columns. Various chromatographic performance indicators, such as inertness, and thermal and chemical stability, were confirmed to be unaffected by using this interface at an elevated temperature of around 300 degrees C. The new interface should facilitate the characterization of polymeric materials using analytical pyrolysis techniques in which frequent switching is required in the measuring mode, such as evolved gas analysis-MS and flash pyrolysis-GC-MS. PMID- 22076335 TI - Analysis of bromate in drinking water using liquid chromatography-tandem mass spectrometry without sample pretreatment. AB - An analytical method for determining bromate in drinking water was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The (18)O enriched bromate was used as an internal standard. The limit of quantification (LOQ) of bromate was 0.2 ug/L. The peak of bromate was separated from those of coexisting ions (i.e., chloride, nitrate and sulfate). The relative and absolute recoveries of bromate in two drinking water samples and in a synthesized ion solution (100 mg/L chloride, 10 mg N/L nitrate, and 100 mg/L sulfate) were 99-105 and 94-105%, respectively. Bromate concentrations in 11 drinking water samples determined by LC-MS/MS were <0.2-2.3 ug/L. The results of the present study indicated that the proposed method was suitable for determining bromate concentrations in drinking water without sample pretreatment. PMID- 22076336 TI - Moment analysis of chromatographic behavior of superficially porous particles. AB - Peak parking experiments were conducted to study the chromatographic behavior in a RPLC system consisting of a column packed with superficially porous C(18) particles and a mixture of methanol and water (70/30, v/v). The values of the surface diffusion coefficient and the retention equilibrium constant of a column packed with superficially porous C(18)-particles were comparable to those of columns packed with a C(18)-silica monolith and full-porous C(18)-silica gel particles. The flow-rate dependence of HETP was hypothetically calculated by using moment equations to clarify the influence of the structural characteristics on the chromatographic behavior. The column efficiency of a column packed with the superficially porous particles is higher in the high flow-rate range than that with full-porous spherical particles. This is attributed to the smaller contribution of the intraparticulate mass transfer in the superficially porous particles to band broadening. The moment equations are effective for the quantitative analysis of chromatographic behavior of superficially porous particles. PMID- 22076337 TI - Sol-gel titania-coated needles for solid phase dynamic extraction-GC/MS analysis of desomorphine and desocodeine. AB - Novel sol-gel titania film coated needles for solid-phase dynamic extraction (SPDE)-GC/MS analysis of desomorphine and desocodeine are described. The high thermal stability of titania film permits efficient extraction and analysis of poorly volatile opiate drugs. The influences of sol-gel reaction time, coating layer, extraction and desorption time and temperature on the SPDE needle performance were investigated. The deuterium labeled internal standard was introduced either during the extraction of analyte or directly injected to GC after the extraction process. The latter method was shown to be more sensitive for the analysis of water and urine samples containing opiate drugs. The proposed conditions provided a wide linear range (from 5-5000 ppb), and satisfactory linearity, with R(2) values from 0.9958 to 0.9999, and prominent sensitivity, LOQs (1.0-5.0 ng/g). The sol-gel titania film coated needle with SPDE-GC/MS will be a promising technique for desomorphine and desocodeine analysis in urine. PMID- 22076338 TI - Determination of isoliquiritigenin and its distribution in mice by synchronous fluorescence spectrometry. AB - The aim of the present work was to develop a new method using synchronous fluorescence spectrometry (SFS) to determine the concentration of isoliquiritigenin (ISL) in mouse blood and tissues, and to investigate ISL's distribution among organs after an intraperitoneal (IP) dose of ISL. The synchronous fluorescence method was optimized with the sample pH, stability, metal ions, concentration of Al(3+), and surfactants. The proposed method was used to determine the ISL concentration in mouse blood, brain, heart, kidney, liver, spleen and lung after an IP injection of ISL. The optimal conditions for the determination of ISL using SFS were found to be: excitation and emission wavelengths of 469 and 557 nm, respectively; the use of 3% AlCl(3) as a fluorescence intensity enhancer; measuring samples within 1 h of collection, sample pH 7-8, isolation of samples from surfactants; and wavelength interval (Deltalambda) = 70 nm. After IP injection, the distribution of ISL in mouse organs was: liver > kidney > spleen > blood > lung > brain > heart. The blood concentration of ISL peaked at 60 min; concentrations of ISL in liver, kidney and spleen achieved maxima at 120 min. SFS provides a simple, but effective analytical method that will benefit the study of in vivo biological effects of ISL, including absorption, distribution, metabolism, and excretion. PMID- 22076339 TI - Determination of dissolved oxygen in water based on its quenching effect on the fluorescent intensity of bis(2,2'-bipyridine)-5-amino-1,10-phenanthroline ruthenium complex. AB - A water-soluble fluorescence dye, bis(2,2'-bipyridine)-5-amino-1,10 phenanthroline ruthenium complex (Ru(bpy)(2)(5-NH(2)-1,10-phen)), was synthesized and used as a fluorescence probe for detecting dissolved oxygen in water. The fluorescence intensity of the probe in different dissolved-oxygen concentrations was investigated. The sensitivity of the probe was evaluated in terms of the ratio I(N(2))/I(O(2)), where I(N(2)) and I(O(2)) correspond to the detected fluorescence intensity of nitrogen and oxygen-saturated solutions, respectively. The experimental results showed that the probe yielded a linear Stern-Volmer plot, and had a I(N(2))/I(O(2)) ratio of about 5.2. The detection limit, defined as three-times the standard deviation, was 8.6 * 10(-7) mol L(-1) after eleven determinations of nitrogen-saturated blank solutions. Additionally, the probe was pH-insensitive and ionic strength-independent with good characteristics of practicality and selectivity. PMID- 22076340 TI - Quantitation of surface-bound proteins on biochips using MALDI-TOF MS. AB - We report on a novel method for the quantitation of proteins specifically bound on a ligand-presenting biochip by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). The bound protein was digested by trypsin, and the resulting peptide fragments were analyzed by MALDI TOF MS in the presence of an isotope-labeled internal standard (IS). The IS has the same sequence as a reference peptide (RP) of the target protein digest, but a different molecular weight. The absolute amount of the specifically bound protein on a biochip is then quantitated by comparison of mass intensities between the RP and the IS. Because they have the same molecular milieu, the mass intensities of these two analytes represent the real amounts of analytes on the chip. As a model system, we tested glutathione s-transferase (GST) and a GST fusion protein, which were captured on glutathione-presenting biochips. We observed that the glutathione densities on biochips showed a good correlation with the absolute quantity of the proteins. We believe that our method will provide an alternative to currently existing tools for the absolute quantitation of surface-bound proteins. PMID- 22076341 TI - Sorption characteristics of caffeine onto untreated polyurethane foam: application to its determination in human plasma. AB - In the present paper, the sorption properties of caffeine (CAF) onto polyether type polyurethane foam (PUF) as solid phase sorbent were investigated with UV determination at 274.3 nm. Batch and column methods were used to optimize chemical, flow, kinetic and isothermal conditions for preconcentration of CAF. Results indicated quantitative sorption of CAF at pH 8 and 30 min shaking time. The maximum sorption capacity was found to be 4.1 mg g(-1). Column preconcentration was recommended at a flow rate of 1.5 mL min(-1) and desorption with 4 mL from 0.15 mol L(-1) hydrochloric acid. The procedure provided a linear analytical range of 0.05-30 mg L(-1). The detection and quantification limits are 0.016 and 0.047 mg L(-1), respectively. The procedure was applied to determination of CAF in spiked human plasma. The obtained recoveries were 98-101% and RSD values were from 0.05 to 9.5%. PMID- 22076342 TI - Pressure-induced structural and hydration changes of proteins in aqueous solutions. AB - The effects of elevated hydrostatic pressure on four representative proteins, lysozyme, human serum albumin, ubiquitin and RNase A, were investigated by using Fourier transform infrared (FTIR) spectroscopy, by principal component analysis (PCA) and by moving-window two-dimensional (MW2D) correlation analysis. In addition, we revealed the pressure-induced changes of secondary structure elements using curve fitting. With pressure increase, the amide I band shifted to lower wavenumbers, with a transition at 200 MPa, which was indicative of hydration enhancement. Moreover, the pressure-induced behavior of pure water was studied, similar transition pressure was observed with protein in aqueous solution, suggesting that structure change of water around 200 MPa caused a hydration enhancement of protein. Under pressure higher than 200 MPa, the structural changes of the four proteins were obviously different except for the common features shifting to lower wavenumbers with pressure, basically due to the distinct structural differences among them. PMID- 22076343 TI - Sensitivity variation for H, B, Si, Cl, Ca and Cd in solid materials by prompt gamma-ray analysis with a special emphasis on the presence of hydrogen. AB - The effects of neutron scattering by matrix hydrogen in geological samples were examined in order to accurately determine their chemical compositions by neutron induced prompt gamma-ray analysis (PGA). Three different matrix materials including basaltic reference rock sample (JB-2) mixed with chemical reagents including H-containing ones were analyzed by using thermal and/or cold neutron guided beams of JRR-3 at Japan Atomic Energy Agency. The sensitivity change of elements with the variation of the H concentrations was evaluated for disk and spherical target geometries. The results show that the analytical sensitivities of B, Cl and Cd in disk samples seem to increase with increasing the matrix H concentrations by the irradiation of both thermal and cold-neutron beams. The sensitivity enhancement of B for disk-shaped JB-2 mixed with up to 2% mass H is within the analytical uncertainty associated with PGA with a thermal-neutron beam. PMID- 22076344 TI - Development of a certified reference material (NMIJ CRM 7505-a) for the determination of trace elements in tea leaves. AB - A certified reference material (CRM) for trace elements in tea leaves has been developed in National Metrology Institute of Japan (NMIJ). The CRM was provided as a dry powder (<90 um) after frozen pulverization of washed and dried fresh tea leaves from a tea plant farm in Shizuoka Prefecture, Japan. Characterization of the property value for each element was carried out exclusively by NMIJ with at least two independent analytical methods, including inductively coupled plasma mass spectrometry (ICP-MS), high-resolution (HR-) ICP-MS, isotope-dilution (ID-) ICP-MS, inductively coupled plasma optical emission spectrometry (ICP-OES), graphite-furnace atomic-absorption spectrometry (GF-AAS) and flame atomic absorption spectrometry (FAAS). Property values were provided for 19 elements (Ca, K, Mg, P, Al, B, Ba, Cd, Cu, Fe, Li, Mn, Na, Ni, Pb, Rb, Sr, Zn and Co) and informative values for 18 elements (Ti, V, Cr, Y, and all of the lanthanides, except for Pm whose isotopes are exclusively radioactive). The concentration ranges of property values and informative values were from 1.59% (mass) of K to 0.0139 mg kg(-1) of Cd and from 0.6 mg kg(-1) of Ti to 0.0014 mg kg(-1) of Lu, respectively. Combined relatively standard uncertainties of the property values were estimated by considering the uncertainties of the homogeneity, analytical methods, characterization, calibration standard, and dry-mass correction factor. The range of the relative combined standard uncertainties was from 1.5% of Mg and K to 4.1% of Cd. PMID- 22076345 TI - Voltammetric evaluation on poly alpha-aspartic acid-zinc ion complex in the helix coil transition pH region. AB - Helix-coil transitions of poly alpha-aspartic acid (PASP) were studied by dc polarography in the presence of Zn(2+) as a marker attached to the polymer. The diffusion current (i(d)) of Zn(2+) declined markedly in the pH range of 3.5-7.4 due to a formation of metal ion-PASP macromolecular complexes. The complex formation also reflects on an increase of the magnitude at ca. 222 nm of CD spectrum, suggesting that PASP forms the helix structure by coordination of Zn(2+) in the corresponding pH region. Helix content, determined by the decrease in i(d) of Zn(2+), corresponds favorably to that by CD measurements. In the lower acidic pH region, the coordination mode of Zn(2+) to PASP is different from that at neutral pH region. The decrease in i(d) of Zn(2+) is independent of the further formation of helix structure. Zn(2+) coordinates with sparsely dissociated carboxylate groups of the helical part of PASP, which bring about an aggregation of polypeptide strands. The diffusion current of the ion attached to the polymer, therefore, is a parameter sensitive to conformational changes of PASP from acidic through neutral pH region. PMID- 22076346 TI - Rethinking the science system. PMID- 22076351 TI - Environmental science. China to spend billions cleaning up groundwater. PMID- 22076353 TI - Atmospheric science. NSF to turn tank killer into storm chaser. PMID- 22076352 TI - Sustainability. Seafood eco-label grapples with challenge of proving its impact. PMID- 22076354 TI - Newsmaker interview: Henry Markram. Blue Brain founder responds to critics, clarifies his goals. Interview by Greg Miller. PMID- 22076355 TI - U.S. science and austerity. Fewer dollars, forced choices. PMID- 22076356 TI - U.S. science and austerity. Setting priorities has never been fun. PMID- 22076357 TI - U.S. science and austerity. Darwinism vs. social engineering at NIH. PMID- 22076358 TI - U.S. science and austerity. Commitments, ideology clash over DOE research spending. PMID- 22076359 TI - U.S. science and austerity. NSF goes back to basics to preserve basic research. PMID- 22076360 TI - U.S. science and austerity. A difficult view from space for NOAA. PMID- 22076361 TI - U.S. science and austerity. Will tight budgets sink NASA flagships? PMID- 22076362 TI - Competencies: a cure for pre-med curriculum. PMID- 22076363 TI - Drawing attention to diagram use. PMID- 22076365 TI - Climate change. Is weather event attribution necessary for adaptation funding? PMID- 22076366 TI - Evolution. Living fossil younger than thought. PMID- 22076367 TI - Materials science. Toward high-throughput zeolite membranes. PMID- 22076368 TI - Cell biology. Anatomy of prostaglandin signals. PMID- 22076369 TI - Cell biology. Pyro-technic control of metabolism. PMID- 22076370 TI - Ecology. Mosquito trials. PMID- 22076371 TI - Direct observation of molecular preorganization for chirality transfer on a catalyst surface. AB - The chemisorption of specific optically active compounds on metal surfaces can create catalytically active chirality transfer sites. However, the mechanism through which these sites bias the stereoselectivity of reactions (typically hydrogenations) is generally assumed to be so complex that continued progress in the area is uncertain. We show that the investigation of heterogeneous asymmetric induction with single-site resolution sufficient to distinguish stereochemical conformations at the submolecular level is finally accessible. A combination of scanning tunneling microscopy and density functional theory calculations reveals the stereodirecting forces governing preorganization into precise chiral modifier substrate bimolecular surface complexes. The study shows that the chiral modifier induces prochiral switching on the surface and that different prochiral ratios prevail at different submolecular binding sites on the modifier at the reaction temperature. PMID- 22076373 TI - Forecasting fire season severity in South America using sea surface temperature anomalies. AB - Fires in South America cause forest degradation and contribute to carbon emissions associated with land use change. We investigated the relationship between year-to-year changes in fire activity in South America and sea surface temperatures. We found that the Oceanic Nino Index was correlated with interannual fire activity in the eastern Amazon, whereas the Atlantic Multidecadal Oscillation index was more closely linked with fires in the southern and southwestern Amazon. Combining these two climate indices, we developed an empirical model to forecast regional fire season severity with lead times of 3 to 5 months. Our approach may contribute to the development of an early warning system for anticipating the vulnerability of Amazon forests to fires, thus enabling more effective management with benefits for climate and air quality. PMID- 22076372 TI - N2reduction and hydrogenation to ammonia by a molecular iron-potassium complex. AB - The most common catalyst in the Haber-Bosch process for the hydrogenation of dinitrogen (N(2)) to ammonia (NH(3)) is an iron surface promoted with potassium cations (K(+)), but soluble iron complexes have neither reduced the N-N bond of N(2) to nitride (N(3-)) nor produced large amounts of NH(3) from N(2). We report a molecular iron complex that reacts with N(2) and a potassium reductant to give a complex with two nitrides, which are bound to iron and potassium cations. The product has a Fe(3)N(2) core, implying that three iron atoms cooperate to break the N-N triple bond through a six-electron reduction. The nitride complex reacts with acid and with H(2) to give substantial yields of N(2)-derived ammonia. These reactions, although not yet catalytic, give structural and spectroscopic insight into N(2) cleavage and N-H bond-forming reactions of iron. PMID- 22076374 TI - Phase transition of FeO and stratification in Earth's outer core. AB - Light elements such as oxygen in Earth's core influence the physical properties of the iron alloys that exist in this region. Describing the high-pressure behavior of these materials at core conditions constrains models of core structure and dynamics. From x-ray diffraction measurements of iron monoxide (FeO) at high pressure and temperature, we show that sodium chloride (NaCl)-type (B1) FeO transforms to a cesium chloride (CsCl)-type (B2) phase above 240 gigapascals at 4000 kelvin with 2% density increase. The oxygen-bearing liquid in the middle of the outer core therefore has a modified Fe-O bonding environment that, according to our numerical simulations, suppresses convection. The phase induced stratification is seismologically invisible but strongly affects the geodynamo. PMID- 22076375 TI - Aerosol indirect effect on biogeochemical cycles and climate. AB - The net effect of anthropogenic aerosols on climate is usually considered the sum of the direct radiative effect of anthropogenic aerosols, plus the indirect effect of these aerosols through aerosol-cloud interactions. However, an additional impact of aerosols on a longer time scale is their indirect effect on climate through biogeochemical feedbacks, largely due to changes in the atmospheric concentration of CO(2). Aerosols can affect land and ocean biogeochemical cycles by physical forcing or by adding nutrients and pollutants to ecosystems. The net biogeochemical effect of aerosols is estimated to be equivalent to a radiative forcing of -0.5 +/- 0.4 watts per square meter, which suggests that reaching lower carbon targets will be even costlier than previously estimated. PMID- 22076376 TI - Global DNA demethylation during mouse erythropoiesis in vivo. AB - In the mammalian genome, 5'-CpG-3' dinucleotides are frequently methylated, correlating with transcriptional silencing. Genome-wide demethylation is thought to occur only twice during development, in primordial germ cells and in the pre implantation embryo. These demethylation events are followed by de novo methylation, setting up a pattern inherited throughout development and modified only at tissue-specific loci. We studied DNA methylation in differentiating mouse erythroblasts in vivo by using genomic-scale reduced representation bisulfite sequencing (RRBS). Demethylation at the erythroid-specific beta-globin locus was coincident with global DNA demethylation at most genomic elements. Global demethylation was continuous throughout differentiation and required rapid DNA replication. Hence, DNA demethylation can occur globally during somatic cell differentiation, providing an experimental model for its study in development and disease. PMID- 22076377 TI - Influence of inositol pyrophosphates on cellular energy dynamics. AB - With its high-energy phosphate bonds, adenosine triphosphate (ATP) is the main intracellular energy carrier. It also functions in most signaling pathways, as a phosphate donor or a precursor for cyclic adenosine monophosphate. We show here that inositol pyrophosphates participate in the control of intracellular ATP concentration. Yeasts devoid of inositol pyrophosphates have dysfunctional mitochondria but, paradoxically, contain four times as much ATP because of increased glycolysis. We demonstrate that inositol pyrophosphates control the activity of the major glycolytic transcription factor GCR1. Thus, inositol pyrophosphates regulate ATP concentration by altering the glycolytic/mitochondrial metabolic ratio. Metabolic reprogramming through inositol pyrophosphates is an evolutionary conserved mechanism that is also preserved in mammalian systems. PMID- 22076378 TI - Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. AB - Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg(105)) and tyrosine residue (Tyr(102)) in the acyl pocket of Sirt5. Several mammalian proteins were identified with mass spectrometry to have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice appeared to increase the level of succinylation on carbamoyl phosphate synthase 1, which is a known target of Sirt5. Thus, protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo. PMID- 22076379 TI - tRNAs marked with CCACCA are targeted for degradation. AB - The CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase] adds CCA to the 3' ends of transfer RNAs (tRNAs), a critical step in tRNA biogenesis that generates the amino acid attachment site. We found that the CCA-adding enzyme plays a key role in tRNA quality control by selectively marking structurally unstable tRNAs and tRNA-like small RNAs for degradation. Instead of adding CCA to the 3' ends of these transcripts, CCA-adding enzymes from all three kingdoms of life add CCACCA. In addition, hypomodified mature tRNAs are subjected to CCACCA addition as part of a rapid tRNA decay pathway in vivo. We conjecture that CCACCA addition is a universal mechanism for controlling tRNA levels and preventing errors in translation. PMID- 22076381 TI - Attention but not awareness modulates the BOLD signal in the human V1 during binocular suppression. AB - Although recent psychophysical studies indicate that visual awareness and top down attention are two distinct processes, it is not clear how they are neurally dissociated in the visual system. Using a two-by-two factorial functional magnetic resonance imaging design with binocular suppression, we found that the visibility or invisibility of a visual target led to only nonsignificant blood oxygenation level-dependent (BOLD) effects in the human primary visual cortex (V1). Directing attention toward and away from the target had much larger and robust effects across all study participants. The difference in the lower-level limit of BOLD activation between attention and awareness illustrates dissociated neural correlates of the two processes. Our results agree with previously reported V1 BOLD effects on attention, while they invite a reconsideration of the functional role of V1 in visual awareness. PMID- 22076380 TI - A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A. AB - The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1. PMID- 22076382 TI - Survivin deficiency induces apoptosis and cell cycle arrest in HepG2 hepatocellular carcinoma cells. AB - The postulated dual roles of survivin as an anti-apoptotic factor and a mitotic inducer have placed this factor in the spotlight of cancer research. The purpose of this study was to investigate whether survivin might connect the cell cycle with apoptosis. Here, by simultaneously monitoring survivin deficiency-induced morphological changes of HepG2 cells using time-lapse imaging as well as determining apoptosis progression, we observed synchronized defective mitosis characterized by multinucleated and polyploid cells and cell cycle arrest at S phase or G2/M phase followed by apoptosis, the processes of which depended on the simultaneous destruction of specialized subcellular compartments of survivin and activation of caspase-3-like protease. These findings showed that the survivin protein acted as mitotic regulator and apoptosis inhibitor, but may also possess the role of a bridge in integrating apoptosis and cell division. An essential prerequisite of this pathway was the specialized subcellular localization of survivin. The overexpression of survivin was required to maintain cell viability and proper cell cycle transitions, and to preserve genetic fidelity during cell division in HepG2 cells. PMID- 22076383 TI - Surface acoustic wave induced particle manipulation in a PDMS channel--principle concepts for continuous flow applications. AB - A device for acoustic particle manipulation in the 40 MHz range for continuous flow operation in a 50 MUm wide PDMS channel has been evaluated. Unidirectional interdigital transducers on a Y-cut Z-propagation lithium nixobate wafer were used to excite a surface acoustic wave that generated an acoustic standing wave inside the microfluidic channel. It was shown that particle alignment nodes with different inter-node spacing could be obtained, depending on device design and driving frequency. The observed inter-node spacing differed from the standard half-wavelength inter-node spacing generally employed in bulk acoustic transducer excited resonant systems. This effect and the related issue of acoustic node positions relative the channel walls, which is fundamental for most continuous flow particle manipulation operations in channels, was evaluated in measurements and simulations. Specific applications of particle separation and alignment where these systems can offer benefits relative state-of the art designs were identified. PMID- 22076385 TI - Uric acid level and its association with carotid intima-media thickness in patients with cardiac syndrome X. AB - OBJECTIVE: The aim of our study was to evaluate serum uric acid level and its relationship with carotid intima-media thickness (CIMT) in patients with cardiac syndrome X (CSX). SUBJECTS AND METHODS: A total of 50 patients with CSX (28 females/22 males, 51.0 +/- 10.9 years) and 40 controls (27 females/13 males, 53.0 +/- 10.2 years) were included in the study. All subjects underwent a noninvasive stress test and conventional coronary angiography. Serum uric acid levels were measured and B mode ultrasonography was performed to assess CIMT in all subjects. RESULTS: Serum uric acid levels were higher in patients with CSX than in the control subjects (5.1 +/- 1.8 vs. 3.9 +/- 1.3 mg/dl; p = 0.002). The CIMT was higher in patients with CSX than in the control subjects (0.75 +/- 0.18 vs. 0.63 +/- 0.09 mm; p < 0.001). A significant correlation was found between serum uric acid values and CIMT measurements in patients with CSX (r = 0.666, p < 0.001). CONCLUSIONS: Serum uric acid levels were higher in patients with CSX and elevated serum uric acid levels were associated with carotid atherosclerosis, thereby indicating that elevated serum uric acid levels might contribute to the development of subclinical atherosclerosis in CSX patients. PMID- 22076386 TI - Angelica sinensis suppresses human lung adenocarcinoma A549 cell metastasis by regulating MMPs/TIMPs and TGF-beta1. AB - In this study we investigated the potential effects of Angelica sinensis on the growth and metastasis in human lung adenocarcinoma A549 cells. In vitro the Cck-8 assays showed that Angelica sinensis had weak antiproliferative effect on A549 cells only at high concentration. The cell adhesion assay showed that Angelica sinensis decreased the adhesive ability of A549 cells in a dose- and time dependent manner. Transwell invasion and migration assay showed that Angelica sinensis reduced the invasive and migratory abilities of A549 cells in a dose dependent manner. In vivo the animal experiments showed that Angelica sinensis suppressed lung metastasis of nude mice at high concentration. Then, we attempted to clarify the mechanisms of anti-metastatic activities of Angelica sinensis. The results showed Angelica sinensis inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), it involved the down-regulation of the expressions of MMP-2 and MMP-9 at both the protein and mRNA levels, which may be associated with Angelica sinensis suppressing the expression of TGF-beta1. It also involved the increase of the tissue inhibitors of metalloproteinases TIMP-2, but TIMP-1 decreased upon incubation of A549 cells with Angelica sinensis. The results suggest that Angelica sinensis might exert anti-growth and anti-metastasis activity against lung cancer cells through the decrease of MMP-2, MMP-9, TGF-beta1 and TIMP-1 and increase of TIMP-2. PMID- 22076387 TI - The role of the tumor suppressor RUNX3 in giant cell tumor of the bone. AB - RUNX3 is a tumor suppressor gene localized in 1p36. In various human tumors, the region is frequently inactivated through hypermethylation, histone modulation and other processes. Recent studies have suggested that loss of RUNX3 expression is involved in stomach, colon and breast cancer. However, the relationship between RUNX3 expression and giant cell tumor of the bone (GCTB) remains elusive. The aim of our study was to elucidate the roles of RUNX3 expression in carcinogenesis and progression of giant cell tumor of the bone. The levels of RUNX3 mRNA and protein were evaluated in human GCTB specimens and cell lines. To assess RUNX3 methylation we employed methylation-specific polymerase chain reaction using GCTB specimens and cell lines. In addition, to examine the roles of RUNX3 in giant cell tumor of the bone, GCTB cells were transfected with pcDNA3.1-RUNX3 (RUNX3 was cloned into the pcDNA3.1 plasmid). Flow cytometry (FCM) was used to analyze the apoptosis and cell cycle. The mobility of cells was tested by transwell migration assay. The expression rates of RUNX3 in patients with GCTB were significanly lower than normal bone tissues. Thirty of 47 human cancer specimens exhibited suppression (P<0.05). Down-regulation of RUNX3 mRNA in the same GCTB cell lines was associated with RUNX3 DNA methylation. In in vitro experiments, exogenous expression of RUNX3 strongly inhibited cell growth in GCTB by MTT (P<0.05), induced apoptosis as evidenced by Annexin V-FITC and increased G1 phase ratio by PI (P<0.05). Transwell migration assay showed that less RUNX3 positive cells migrated to the lower side of the membrane than negative ones (P<0.05). These results show that RUNX3 is a tumor suppressor in GCTB. RUNX3 DNA methylation may be the molecular basis for its lower expression. These data may be applied in GCTB for diagnostics and therapeutics. PMID- 22076389 TI - Anemias: road signs to the real problems. AB - Anemia comes in many forms, always indicating an underlying problem. Expand your ability to recognize and cope with this condition by learning the main types of anemia along with their causes, distinguishing traits, and treatments. PMID- 22076392 TI - Fosphenytoin. PMID- 22076388 TI - Pulmonary toxicities from targeted therapies: a review. AB - Pulmonary toxicity is rarely seen with most commonly used targeted therapies. The endothelial growth factor receptor (EGFR) small-molecule tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib can cause interstitial lung disease (ILD). BCR-ABL tyrosine kinase inhibitors imatinib and dasatinib can cause pleural effusions. Infusion-related bronchospasm is common with the monoclonal antibodies to EGFR cetuximab and panitumumab, and case reports of bronchiolitis and pulmonary fibrosis have been described. Up to one-sixth of patients taking mammalian target of rapamycin (mTOR) inhibitors get a reversible interstitial pneumonitis. Bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), has been associated with hemoptysis and pulmonary embolism particularly in patients with squamous cell lung cancer. Infusion-related bronchospasms, acute respiratory distress syndrome (ARDS), and interstitial pneumonitis can be seen with the anti-lymphocyte monoclonal antibodies rituximab, ofatumumab, and alemtuzumab. While most pulmonary toxicities from these therapies are mild and resolve promptly with dose reduction or discontinuation, it is important for the clinician to recognize these potential toxicities when faced with treatment-related complications. Discerning these pulmonary adverse effects may help in making decisions on diagnostic testing and therapy, particularly for those with pulmonary and cardiovascular co-morbidities. PMID- 22076393 TI - Assessing and managing the patient with headaches. AB - Headaches are considered the most common type of pain; more than 40 million Americans seek treatment each year. A clear understanding of the types and possible causes of headache pain is essential to adequately assess and manage the patient with headaches. Headaches can be categorized as either primary or secondary to an underlying and usually treatable cause. Most headaches are primary; this includes migraine and variants, and cluster and tension-type headaches. Before assuming a primary diagnosis, however, the clinician must rule out headaches secondary to an underlying cause so that further investigation, treatment, or referral may be initiated. PMID- 22076394 TI - Recognizing the various presentations of appendicitis. AB - Appendicitis must be considered in the differential diagnosis of any patient presenting with abdominal pain. But inconsistencies in presentation, especially among the young and the elderly, can lead to errors in diagnosis. This article describes the pathophysiology, diagnosis, and treatment of appendicitis. PMID- 22076395 TI - The loyal treatment: how dedicated employees benefit managers and organizations. AB - Despite employees' diminished loyalty to health care organizations, nurse managers can earn employees' devotion and transfer the benefits to the organization. PMID- 22076396 TI - Plunging into preload and afterload. AB - Tools for teaching new nurses surround you in the intensive care unit. This article presents a simple exercise using readily available supplies to help nurses gain a solid understanding of preload and afterload. PMID- 22076397 TI - Resources for managing migraines. PMID- 22076399 TI - Tips for succeeding at Internet courses. AB - Ready to go to "cyberschool"? Here's practical advice on making it work for you. PMID- 22076400 TI - Head of bed elevation, early walking, and patient comfort after percutaneous transluminal coronary angioplasty. AB - Several studies have investigated head elevation, early walking, and patient comfort after percutaneous transluminal coronary angioplasty. This research analysis reviews this procedure's current practices and related complications. The authors analyzed the studies' methodologies, grouped the findings according to similar objectives, and highlighted implications for nursing practice and patient care. PMID- 22076401 TI - Antibiotic resistance: time to fight back. PMID- 22076402 TI - Fault diagnosis of a benchmark fermentation process: a comparative study of feature extraction and classification techniques. AB - This paper investigates fault diagnosis in batch processes and presents a comparative study of feature extraction and classification techniques applied to a specific biotechnological case study: the fermentation process model by Birol et al. (Comput Chem Eng 26:1553-1565, 2002), which is a benchmark for advanced batch processes monitoring, diagnosis and control. Fault diagnosis is achieved using four approaches on four different process scenarios based on the different levels of noise so as to evaluate their effects on the performance. Each approach combines a feature extraction method, either multi-way principal component analysis (MPCA) or multi-way independent component analysis (MICA), with a classification method, either artificial neural network (ANN) or support vector machines (SVM). The performance obtained by the different approaches is assessed and discussed for a set of simulated faults under different scenarios. One of the faults (a loss in mixing power) could not be detected due to the minimal effect of mixing on the simulated data. The remaining faults could be easily diagnosed and the subsequent discussion provides practical insight into the selection and use of the available techniques to specific applications. Irrespective of the classification algorithm, MPCA renders better results than MICA, hence the diagnosis performance proves to be more sensitive to the selection of the feature extraction technique. PMID- 22076403 TI - Functional consequences of the lack of amyloid precursor protein in the mouse dentate gyrus in vivo. AB - The amyloid precursor protein (APP) plays a crucial role in the pathogenesis of Alzheimer's disease. Here, we studied whether the lack of APP affects the synaptic properties in the dentate gyrus by measuring granule cell field potentials evoked by perforant path stimulation in anesthetized 9-11-month-old APP-deficient mice in vivo. We found decreased paired-pulse facilitation, indicating altered presynaptic short-term plasticity in the APP-deficient dentate gyrus. In contrast, excitatory synaptic strength and granule cell firing were unchanged in APP knockout mice. Likewise, long-term potentiation (LTP) induced by a theta-burst stimulation protocol was not impaired in the absence of APP. These findings suggest that the deletion of APP may affect presynaptic plasticity of synaptic transmission at the perforant path-granule cell synapse but leaves synaptic efficacy intact and LTP preserved, possibly due to functional redundancy within the APP gene family. PMID- 22076404 TI - Tuning of the excitability of transcortical cutaneous reflex pathways during mirror-like activity. AB - Voluntary contraction of a muscle generates electromyographic (EMG) activity in the homologous muscle on the opposite side (mirror-like activity), not only in pathological states and in infants but also in healthy adults. Few studies have examined whether the cutaneous reflexes during the preparatory period of a reaction time task are affected by mirror-like activity. In the present study, we investigated the modulation of the cutaneous reflexes in the left first interosseous (FDI) muscle in 9 healthy subjects while they performed a quick abduction of the right index finger during a reaction time task. Cutaneous reflexes were elicited by applying non-noxious electrical stimulation to the left index finger. We found that mirror-like activity occurred in the left FDI at approximately the onset of EMG activity in the right FDI. The excitatory E2 component was selectively increased at ~75 ms after the "Go" signal, which corresponded to the onset of mirror-like activity. The inhibitory I2 (~90 ms) component was tuned consistently into excitation after the "Go" signal. These findings suggest that long latency reflexes, possibly transcortical cutaneous reflexes, are finely tuned in relation to mirror-like activity. PMID- 22076405 TI - Event-related potentials in adolescents with different cognitive styles: field dependence and field independence. AB - Field dependence/independence (FD/FI) is an important dimension of personality and cognitive styles. Different ability in mobilizing and/or allocating mental attentional capacity was considered to be the most possible explanation for the FDI cognitive style. Many studies on characterizing the functional neuroanatomy of attentional control indicated the existence of a dissociable sub-process of conflict-monitoring and "cognitive control" system. However, little was known about it. We might dissociate "cognitive control" system from conflict processing by taking advantage of the variable of the FDI cognitive style. In addition, essentially cognitive styles (FDI) are often widely studied in psychological and educational fields, but hardly in neuroscience. We speculated that ERP components could help to explain the difference between how FD and FI individuals process information. The purpose of the reported study was to explore the possible relation between the "cognitive control" system and the conflict processing system during stimulus-matching task. We first characterized the standard FD/FI of senior-high-school Han students in grade two in Beijing, China, based on 160 students with similar age, education, living and cultural background. Twenty-six adolescents were selected and divided into two groups (extreme FD group and extreme FI group) according to their Group Embedded Figures Test (GEFT) results (FD: 5-8; FI: 17-19). They were tested on both Wechsler Adult Intelligence Scale (WAIS) and stimulus-matching task. ERP was measured while the subjects performed the stimulus-matching tasks by categorizing two figures that were presented sequentially either as a match (same shape) or as a conflict (different shape) conditions. The results showed that the mean amplitude of N270 in FI group was higher relative to that in FD group at nearly all centrofrontal areas in the conflict condition. We conclude that the FDI cognitive styles could influence the conflict processing by the "cognitive control" system due to the different abilities of FD and FI subjects in mobilizing and/or allocating attentional resources, which can be indexed by N270. PMID- 22076406 TI - Interlimb differences of directional biases for stroke production. AB - Directional preferences during center-out horizontal shoulder-elbow movements were previously characterized for the dominant arm. These preferences were attributed to a tendency to actively accelerate one joint, while exploiting largely passive motion at the other joint. Since the non-dominant arm is known for inefficient coordination of inter-segmental dynamics, here we hypothesized that directional preferences would differ between the arms. A center-out free stroke drawing task was used that allowed freedom in the selection of movement directions. The task was performed both with and without a secondary cognitive task that has been shown to increase directional biases of the dominant arm. Mirror-symmetrical directional preferences were observed in both arms, with similar bias strength and secondary task effects. The preferred directions were characterized by maximal exploitation of interaction torques for movement production, but only in the dominant arm. The non-dominant arm failed to benefit from interaction torques. The results point to a hierarchical architecture of control. At the higher level, a movement capable to perform the task while satisfying preferences in joint control is specified through forward dynamic transformations. This process is mediated for both arms from a common neural network adapted to the dominant arm and, specifically, to its ability to exploit interaction torques. Dynamic transformations that determine actual control commands are specified at the lower level of control. An alternative interpretation that strokes might be planned evenly across directions, and biases emerge during movement execution due to anisotropic resistance of intrinsic factors that do not depend on arm dominance is also discussed. PMID- 22076407 TI - Effects of Galvanic vestibular stimulation on cognitive function. AB - Although imaging studies suggest activation of cortical areas by vestibular input, there is little evidence of an adverse effect of non-veridical vestibular input on cognitive function. To test the hypothesis that degraded vestibular afferent input adversely affects cognition, we compared performance on a cognitive test battery in a group undergoing suprathreshold bilateral bipolar Galvanic vestibular stimulation (GVS) with a control group receiving no GVS or subthreshold stimulation. The battery consisted of six cognitive tests as follows: reaction time, dual tasking, Stroop, mental rotation, perspective-taking and matching-to-sample, as well as a simple visuomotor (manual tracking) task. Subjects performed the test battery before, during and after suprathreshold GVS exposure or subthreshold stimulation. Suprathreshold GVS significantly increased error rate for the match-to-sample and perspective-taking tasks relative to the subthreshold group, demonstrating a negative effect of non-veridical vestibular input in these specific cognitive tasks. Reaction time, dual tasking, mental rotation and manual tracking were unaffected by GVS exposure. The adverse effect of suprathreshold GVS on perspective taking but not mental rotation is consistent with imaging studies, which have demonstrated that egocentric mental transformations (perspective taking) occur primarily in cortical areas that receive vestibular input (the parietal-temporal junction and superior parietal lobule), whereas object-based transformations (mental rotation) occur in the frontoparietal region. The increased error rate during the match-to-sample task is likely due to interference with hippocampal processing related to spatial memory, as suggested by imaging studies on vestibular patients. PMID- 22076409 TI - Cognitive and neurological outcome at the age of 5-8 years of preterm infants with post-hemorrhagic ventricular dilatation requiring neurosurgical intervention. AB - BACKGROUND: Preterm infants with progressive post-hemorrhagic ventricular dilatation (PHVD) in the absence of associated parenchymal lesions may have a normal neurodevelopmental outcome. OBJECTIVES: To evaluate neurodevelopmental and cognitive outcomes among preterm infants with severe intraventricular hemorrhage (IVH) and PHVD requiring neurosurgical intervention. METHODS: 32 preterm infants were admitted to a neonatal intensive care unit with PHVD requiring neurosurgical intervention, and were seen in the follow-up clinic for standardized cognitive, behavioral and neurological assessments between 5 and 8 years of age. Only preterm infants with a gestational age (GA) of <30 weeks, as well as preterm and full-term infants with PHVD and full-term infants with perinatal asphyxia are seen in our follow-up clinic at this age. There were 23 infants with a GA of <30 weeks in this study population. For these 23, matched controls were available and compared with the IVH group. RESULTS: The majority (59.4%) had no impairments. None of the children with grade III and 8 of the 15 children (53%) with grade IV hemorrhage developed cerebral palsy. More subtle motor problems assessed with the Movement-ABC score were seen in 39% (n = 9); the mean IQ of all children was 93.4, and 29% of the children had an IQ of <85 (-1 SD). Timing of intervention did not have a beneficial effect on outcome. With respect to cognition, no significant differences were found between the IVH and the control group. CONCLUSION: The majority of the children in our population had no impairments. Cerebral palsy was not seen in any of the infants with a grade III hemorrhage. PMID- 22076410 TI - Pseudomonas aeruginosa inhibits the growth of Cryptococcus species. AB - Pseudomonas aeruginosa is a ubiquitous and opportunistic bacterium that inhibits the growth of different microorganisms, including Gram-positive bacteria and fungi such as Candida spp. and Aspergillus fumigatus. In this study, we investigated the interaction between P. aeruginosa and Cryptococcus spp. We found that P. aeruginosa PA14 and, to a lesser extent, PAO1 significantly inhibited the growth of Cryptococcus spp. The inhibition of growth was observed on solid medium by the visualization of a zone of inhibition of yeast growth and in liquid culture by viable cell counting. Interestingly, such inhibition was only observed when P. aeruginosa and Cryptococcus were co-cultured. Minimal inhibition was observed when cell-cell contact was prevented using a separation membrane, suggesting that cell contact is required for inhibition. Using mutant strains of Pseudomonas quinoline signaling, we showed that P. aeruginosa inhibited the growth of Cryptococcus spp. by producing antifungal molecules pyocyanin, a redox active phenazine, and 2-heptyl-3,4-dihydroxyquinoline (PQS), an extracellular quorum-sensing signal. Because both P. aeruginosa and Cryptococcus neoformans are commonly found in lung infections of immunocompromised patients, this study may have important implication for the interaction of these microbes in both an ecological and a clinical point of view. PMID- 22076411 TI - Neonatal intensive care unit candidemia: epidemiology, risk factors, outcome, and critical review of published case series. AB - Evaluation of epidemiological trends, risk factors, and clinical outcome associated with candidemia at a neonatal intensive care unit is reported. From January 2005 to December 2009, forty candidemia cases were identified. C. albicans and C. parapsilosis were the most common species recovered (69 and 24%, respectively). All C. parapsilosis strains were susceptible to antifungals, whereas, C. albicans exhibited higher resistance rates to azoles. Low birth weight, low gestational age, presence of central lines, endotracheal intubation, total parenteral nutrition, previous use of antibiotics, steroids, previous episode(s) of bacteremia and prolonged stay in intensive care unit were common features associated with candidemia. C. albicans was most often isolated from extremely low birth weight neonates as compared to non-albicans Candida (P < 0.01). Mortality rate was 35.7% and was associated with low gestational age (P < 0.01), low birth weight (P < 0.01), and presence of renal failure (P < 0.05). Furthermore, a critical review of recent published case series is presented. PMID- 22076412 TI - Color vision in an elderly patient with protanopic genotype and successfully treated unilateral age-related macular degeneration. AB - We investigated differences in color discrimination between the fellow eye and the affected eye successfully treated for unilateral age-related macular degeneration (AMD) in a 69-year-old male patient with protanopia. His best corrected visual acuity (BCVA) was 1.2 in the right eye (RE) and 0.2 in the left eye (LE). Fundus and angiographic findings showed classic choroidal neovascularization (CNV) secondary to AMD in the LE. BCVA of the LE improved to 0.4, and CNV resolved by 15 months after initiating combined anti-vascular endothelial growth factor and photodynamic therapies. After CNV closure, the Farnsworth dichotomous was performed, showing confusion patterns of the protan axis in either eye. The Farnsworth-Munsell 100-hue test showed a total error score of 520 in the LE, much higher than the score of 348 in the RE. Complete genotypes of the long-wavelength-sensitive (L-) cone and middle-wavelength sensitive (M-) cone opsin genes were determined by polymerase chain reaction, revealing that the patient had a single 5' L-M 3' hybrid gene (encoding an M-cone opsin), with this genotype responsible for protanopia (the L-cone opsin gene was non-functional), instead of the L-cone and M-cone opsin gene arrays. Poorer color vision discrimination in the LE than the RE remained present despite closure of CNV. The presence and type of congenital color vision defect can be confirmed using molecular genetic testing even if complications of acquired retinal diseases such as AMD are identified. PMID- 22076414 TI - Risk factors for persistent candidemia infection in a neonatal intensive care unit and its effect on mortality and length of hospitalization. AB - OBJECTIVE: Candida infections cause substantial morbidity and mortality in neonates. Persistent candidemia has not been associated with increased risk of mortality compared with candidemia of shorter duration. This study sought to determine whether persistent candidemia was associated with increased length of hospitalization or mortality in neonates. STUDY DESIGN: A chart review was conducted of neonates with Candida bloodstream infections (n=37). Demographic, laboratory, pharmacy, nutrition and discharge data were abstracted. Contingency table analysis and logistic regression were used to analyze variables associated with persistent candidemia and mortality. The relationship between length of hospitalization and persistent candidemia was assessed with k-sample equality of medians test. RESULT: Nine patients (24%) had persistent candidemia. Increased time between blood culture draw and initial antifungal therapy was associated with increased incidence of persistent candidemia (P=0.03). Five patients (14%) died before hospital discharge; however, no deaths were attributed to persistent candidemia. Length of hospitalization was not increased with persistent candidemia. A decrease in the ratio of enteral feeding days to hyperalimentation days before collection of the first positive blood culture was significantly associated with an increase in all-cause mortality (P=0.03) and death attributed to candidemia (P=0.04). The risk of all-cause mortality decreased with a history of receiving any enteral feedings before the first positive blood culture (P=0.04), as did death attributed to candidemia (P=0.02). CONCLUSION: A duration of >1 day between the time of blood culture and the initial dose of systemic antifungal treatment places neonates at increased risk for developing persistent candidemia; however, this is not associated with increased mortality. PMID- 22076413 TI - Causes of community stillbirths and early neonatal deaths in low-income countries using verbal autopsy: an International, Multicenter Study. AB - OBJECTIVE: Six million stillbirths (SB) and early neonatal deaths (END) occur annually worldwide, mostly in rural settings distant from health facilities. We used verbal autopsy (VA), to understand causes of non-hospital, community-based SB and END from four low-income countries. STUDY DESIGN: This prospective observational study utilized the train-the-trainer method. VA interviewers conducted standardized interviews; in each country data were reviewed by two local physicians who assigned an underlying causes of deaths (COD). RESULT: There were 252 perinatal deaths (118 END; 134 SB) studied from pooled data. Almost half (45%) the END occurred on postnatal day 1, 19% on the second day and 16% the third day. Major early neonatal COD were infections (49%), birth asphyxia (26%), prematurity (17%) and congenital malformations (3%). Major causes of SB were infection (37%), prolonged labor (11%), antepartum hemorrhage (10%), preterm delivery (7%), cord complications (6%) and accidents (5%). CONCLUSION: Many of these SB and END were from easily preventable causes. Over 80% of END occurred during the first 3 days of postnatal life, and >90% were due to infection, birth asphyxia and prematurity. The causes of SB were more varied, and maternal infections were the most common cause. Increased attention should be targeting at interventions that reduce maternal and neonatal infections and prevent END, particularly during the first 3 days of life. PMID- 22076415 TI - A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. AB - OBJECTIVE: To assess the efficacy and safety of bosentan as an adjuvant therapy of persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: Forty seven neonates with PPHN were randomly assigned to receive either bosentan (n=24) or placebo (n=23). Efficacy was evaluated with a favorable outcome defined as fulfilling all the following criteria (for example, oxygenation index <15, normal pulmonary artery pressure (<20 mm Hg) and no premature discontinuation of the drug because of drug-related toxicity or lack of efficacy). Evaluation of safety was done by monitoring drug-related adverse events. RESULT: Bosentan treatment was superior to placebo with a favorable response in 87.5% of patients treated with bosentan as compared with 20% of those who received placebo (P<0.0001). None of patients in the bosentan group had drug-related clinical or laboratory adverse events. CONCLUSION: Bosentan may be a useful adjuvant therapy of PPHN. PMID- 22076416 TI - The impact of maternal characteristics on the moderately premature infant: an antenatal maternal transport clinical prediction rule. AB - OBJECTIVE: Moderately premature infants, defined here as those born between 300/7 and 346/7 weeks gestation, comprise 3.9% of all births in the United States and 32% of all preterm births. Although long-term outcomes for these infants are better than for less mature infants, morbidity and mortality are still substantially increased in comparison with infants born at term. There is an added survival benefit resulting from birth at a tertiary neonatal care center, and although many of these infants require tertiary level care, delivery at lower level hospitals and subsequent neonatal transfer are still common. Our primary aim was to determine the impact of maternal characteristics and antenatal medical management on the early neonatal course of the moderately premature infant. The secondary aim was to create a clinical prediction rule to determine which infants require intubation and mechanical ventilation in the first 24 h of life. Such a prediction rule could inform the decision to transfer maternal-fetal patients before delivery to a facility with a Level III neonatal intensive care unit (NICU), where optimal care could be provided without the requirement for a neonatal transfer. STUDY DESIGN: Data for this analysis came from the cohort of infants in the Moderately Premature Infant Project (MPIP) database, a multicenter cohort study of 850 infants born at gestational age 300/7 and 346/7 weeks, with birth weight between 591 to 3540 g. [corrected], who were discharged to home alive. We built a logistic regression model to identify maternal characteristics associated with need for tertiary care, as measured by administration of surfactant. Using statistically significant covariates from this model, we then created a numerical decision rule to predict need for tertiary care. RESULT: In multivariate modeling, four factors were associated with reduction in the need for tertiary care, including non-White race (odds ratio (OR)=0.5, (0.3, 0.7)), older gestational age, female gender (OR=0.6 (0.4, 0.8)) and use of antenatal corticosteroids (OR=0.5, (0.3, 0.8)). The clinical prediction rule to discriminate between infants who received surfactant, versus those who did not, had an area under the curve of 0.77 (0.73, 0.8). CONCLUSION: Four antenatal risk factors are associated with a requirement for Level III NICU care as defined by the need for surfactant administration. Future analyses will examine a broader spectrum of antenatal characteristics and revalidate the prediction rule in an independent cohort. PMID- 22076417 TI - Neonates presenting with bloody stools and eosinophilia can progress to two different types of necrotizing enterocolitis. AB - OBJECTIVE: We hypothesized that neonates with bloody stools and concomitant eosinophilia are likely to have atopic enteropathy rather than necrotizing enterocolitis (NEC). STUDY DESIGN: This was a retrospective cross-sectional study using electronic medical records and paper charts. Records of neonates admitted to any Intermountain Healthcare NICU between 1 January 2005 and 30 June 2010 were eligible if 'bloody stools' were listed in any archive. Qualifying records were divided into two groups depending on whether or not within 72 h of passing bloody stool eosinophil counts were above the 95th percentile reference range limit for age. RESULT: Bloody stools were identified in 275 predominantly Caucasian neonates. Fifty-four of these had eosinophilia and 221 had normal eosinophil counts. Those with eosinophilia were born at a slightly younger gestational age (31.3 +/- 4.6 vs 32.6 +/- 4.0 weeks, mean +/- s.d., P=0.032). Contrary to our hypothesis, those with eosinophilia did not have a lower rate of pneumatosis or bowel resection, or death ascribed to NEC. Eosinophilia was more common among those who had a red blood cell (RBC) transfusion within 48 h before passing bloody stools (P<0.001). Those with a recent RBC transfusion were the only neonates to have NEC surgery or to die from NEC. Preceding the bloody stools, those with no antecedent transfusion had been fed a larger volume (P=0.014), and had trends toward receiving calorically enriched feedings (P=0.055) and recent addition of human milk fortifier (P=0.060). Eosinophil counts following RBC transfusion tended to increase for 3-6 days, but when bloody stools were not preceded by transfusion the eosinophil counts were more static over that period. CONCLUSION: In this predominantly Caucasian group of neonates with bloody stools, the presence of eosinophilia did not identify a benign condition distinct from NEC. A total of 44% of these neonates had transfusion-associated NEC. Eosinophils could have a previously unrecognized role in the pathogenesis of this NEC subtype. PMID- 22076418 TI - Meniscus induced self organization of multiple deep concave wells in a microchannel for embryoid bodies generation. AB - Embryonic stem cells (ESCs) have attracted great interest in the fields of tissue engineering, regenerative medicine, and organogenesis for their pluripotency and ability to self-renew. ESC aggregation, which produces an embryoid body (EB), has been widely utilized as a trigger of in vitro directed differentiation. In this paper, we propose a novel method for constructing large numbers of deep concave wells in PDMS microfluidic chips using the meniscus induced by the surface tension of a liquid PDMS prepolymer, and applied this chip for the mass production of uniform sized EBs. To investigate if the microenvironment in the deep concave well is suitable for ES cells, the oxygen diffusion to the deep concave well was analyzed by CFD simulation. Murine EBs were successfully formed in the deep concave wells without loss of cells and laborious careful intervention to refresh culture media. The size of the EBs was uniform, and retrieving of EBs was done just by flipping over the chip. All the processes including EB formation and harvest are easy and safe to cells, and their viability after completion of all processes was over 95%. The basic properties of the EBs were generated and their capacity to differentiate into 3 germ layers was investigated by analyzing the gene expression profile. The harvested EBs were found to differentiate into cardiac cells and neurons, and neurofilaments formed branches of elongated extensions more than 1.0 mm in length. PMID- 22076419 TI - A novel model and molecular therapy for Z alpha-1 antitrypsin deficiency. AB - Animal models that closely resemble human disease can present a challenge. Particularly so in alpha-1 antitrypsin deficiency (alpha(1)ATD), as the mouse alpha-1 antitrypsin (alpha(1)AT) cluster encodes five highly related genes compared with the one in humans. The mouse PI2 homologue is closest to the alpha(1)AT human gene. We have changed the equivalent mouse site that results in the Z variant in man (Glu342Lys) and made both the "M" and "Z" mouse PI2 alpha(1)AT proteins. We have tested the ability of a small-molecular-weight compound CG to alleviate polymerisation of these mouse alpha(1)AT proteins as it has been shown to reduce aggregates of Z alpha(1)AT in man. We found that (1) CG specifically reduces the formation of polymers of recombinant mouse "Z" protein but not "M" protein; (2) whereas there is significantly more alpha(1)AT secreted from Chinese Hamster Ovary cells transfected with the mouse "M" alpha(1)AT gene than with the "Z" (20.8 +/- 3.9 and 6.7 +/- 3.6, respectively; P < 0.005), CG increased the alpha(1)AT levels secreted from "Z" cells (21.2 +/- 0.01) to that of "M" (20.2 +/- 0.02). The data support the concept that the murine "Z" gene is a potential model for the study of alpha(1)ATD and that mice expressing this gene would be relevant for testing treatments in vivo. PMID- 22076420 TI - Annotation of the domestic dog genome sequence: finding the missing genes. AB - There are over 350 genetically distinct breeds of domestic dog that present considerable variation in morphology, physiology, and disease susceptibility. The genome sequence of the domestic dog was assembled and released in 2005, providing an estimated 20,000 protein-coding genes that are a great asset to the scientific community that uses the dog system as a genetic biomedical model and for comparative and evolutionary studies. Although the canine gene set had been predicted using a combination of ab initio methods, homology studies, motif analysis, and similarity-based programs, it still requires a deep annotation of noncoding genes, alternative splicing, pseudogenes, regulatory regions, and gain and loss events. Such analyses could benefit from new sequencing technologies (RNA-Seq) to better exploit the advantages of the canine genetic system in tracking disease genes. Here, we review the catalog of canine protein-coding genes and the search for missing genes, and we propose rationales for an accurate identification of noncoding genes though next-generation sequencing. PMID- 22076421 TI - Hemodynamic influence of tilting disc valve type on pump performance with the NIPRO-ventricular assist device. AB - The NIPRO-ventricular assist device (NIPRO-VAD) is an external pulsatile flow pump. Formerly, Sorin Carbocast, a monoleaflet tilting disc valve (SC valve), was used at the inlet/outlet parts of the pump, but Medtronic Hall (MH valve) is now used. We studied the differences in performance among pumps with different artificial valves. Six NIPRO pumps with SC valves and six with MH valves were examined using mock circuits. The systolic flow of the pump was measured with the ultrasonic flowmeter by changing the systolic fraction. Six patients wearing the NIPRO-VAD underwent periodic pump exchange from a pump with an SC valve to the one with an MH valve. The pump blood flow was measured at pre- and post-pump exchanges using an ultrasonic flowmeter. Blood pressure, serum LDH and AST levels were also compared before and after the pump exchange. Blood flow was significantly increased by using the NIPRO-VAD with the MH valve as compared to the SC valve in vitro. Under the same drive conditions pump flow tended to increase in six patients. No difference was found in patients' blood pressure, serum LDH or AST levels when using the SC or MH valve. From these results, the hemodynamic influence on patients due to replacement of the SC valve with the MH valve in the NIPRO-VAD is considered to be insignificant. PMID- 22076422 TI - Virtual histology evaluation of atherosclerosis regression during atorvastatin and ezetimibe administration: HEAVEN study. AB - BACKGROUND: There is no study focusing on changes in coronary atherosclerosis during dual lipid-lowering therapy with statin and ezetimibe. METHODS AND RESULTS: Eighty-nine patients with stable angina randomized in a 1:1 ratio to Group A (aggressive therapy: atorvastatin 80mg, ezetimibe 10mg) and Group S (standard therapy) were analyzed. Treatment period was 12 months. Coronary arteries were examined by intravascular ultrasound and virtual histology. We found a decrease in the percent atheroma volume (PAV) (-0.4%) in Group A compared with an increase (+1.4%) in Group S (P=0.014) and this was accompanied by an increased frequency of combined atherosclerosis regression (increased lumen volume+decreased PAV) in group A (40.5%) compared with group S (14.9%) (P=0.007). The target low-density lipoprotein cholesterol level <2mmol/L, presence of at least 4 of 5 atherosclerotic risk factors, and decreased level of vascular cellular adhesive molecule were independent predictors of plaque regression. There were no significant differences in plaque composition between the 2 groups over the study duration. However, during analysis of the 2 groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. CONCLUSIONS: Dual lipid-lowering therapy starts atherosclerosis regression, but does not lead to significant changes in plaque composition. The continuous shift in plaque from fibro and fibro-fatty to necrotic with calcification was present in both groups. PMID- 22076423 TI - Current status and trends in the treatment of acute pulmonary thromboembolism. AB - Untreated acute pulmonary thromboembolism (APTE) is associated with high mortality, which is reduced by prompt treatment. Anticoagulation is fundamental in the treatment of APTE and should be initiated from suspicion. The efficacy and safety of novel anticoagulant drugs, such as oral anti-Xa and anti-IIa inhibitors, are topics in the treatment of APTE and are now under investigation. Thrombolytic therapy is a widely accepted treatment strategy for massive APTE, but its use for submassive APTE is controversial. Catheter intervention, percutaneous cardiopulmonary support and surgical embolectomy are also necessary and effective for some patients with APTE. A retrievable inferior vena cava filter is preferred for transient protection against APTE. Some studies have demonstrated the feasibility of outpatient treatment in patients with APTE after risk stratification. PMID- 22076425 TI - Epigenetic alterations in sperm DNA associated with testicular cancer treatment. AB - DNA methylation, a key component of the epigenome involved in regulating gene expression, is initially acquired in the germ line at millions of sites across the genome. Altered sperm methylation patterns are associated with infertility and transgenerational effects in humans and rodents. Testicular cancer is the most common form of cancer among men of reproductive age and has a high cure rate associated with chemotherapy treatment with bleomycin, etoposide, and cis platinum (BEP). Although these drugs result in improved survival, they also affect the number and quality of germ cells. Our goal was to assess germ cell methylation patterns in a rodent model emulating the BEP treatment regimens used in human testicular cancer treatment. Animals were treated with control, or 0.3* (low) or 0.6* (high) dose of BEP, where a 1* dose is equivalent to human treatment regimens. Both dose-dependent and germ cell-dependent DNA methylation alterations were found at numerous loci throughout the genome. Of about 3000 loci tested, 42 loci were affected by BEP at the round spermatid stage of germ cell development, whereas 101 loci were affected in spermatozoa; 15 loci were consistently altered in spermatozoa of all high dose-treated rats. Both hyper- and hypomethylation were detected, suggesting either an interference with normal methylation patterning or abnormal repair of damaged patterns during spermatogenesis. The results indicate that a combination chemotherapy regimen used for testicular cancer treatment can result in altered DNA methylation patterns in spermatozoa and that some loci are more susceptible to damage than others. PMID- 22076426 TI - Bone development in children and adolescents with PKU. AB - INTRODUCTION: Individuals with phenylketonuria (PKU, OMIM 261600) have shown bone disease from childhood. Factors such as non-adherence to treatment, nutritional inadequacy, and high phenylalanine levels are associated with bone disease in several studies. This research aimed to describe the impact of dietary factors (consumption of energy, protein, calcium, phosphorus, and phenylalanine), and the control of plasma phenylalanine levels on bone age (BA) and bone mineral density (BMD). METHODOLOGY: Thirteen patients of both genders, from 8 to 16 years old participated in this study. Control data were collected of phenylalanine levels, food frequency and record, hand and fist X-rays, and spinal bone densitometry. RESULTS: In children group (CG), individuals non-adherent to diet (NAD) consumed lower amounts of calcium (472 +/- 100 mg/day) and energy (1743 +/- 486 Kcal); they had higher rates of phenylalanine (564 +/- 94 MUmol/L) in blood, intake phenylalanine (701 +/- 334 mg/g), and higher protein intake from free foods (14 +/- 6.67 g/day); bone age (BA) values higher than the chronological age (CA) and less BMD values (-0.7 +/- 1.6 SD) also were verified. In adolescent group (AG, N = 8) of NAD, values were lower for energy intake (1379 +/- 258 Kcal), calcium (801 +/- 152 mg/day), phosphorus (657 +/- 102 mg/day), food protein (25 +/- 7.6 g/day), and intake phenylalanine (1067 +/- 382 mg/day) than recommended. Higher levels of plasma phenylalanine (851 +/- 244 MUmol/L), bone age greater than chronological age and lower BMD values (-2.4 +/- -2.5 SD) were observed. CONCLUSION: The results suggest effects on BA and on BMD, in both children and adolescent groups. The bone development is expressed differently in children and adolescents. The non-adherence to the diet verified in both groups and the consequent imbalance in the nutrients intake involved in bone metabolism suggest that these factors influence the failure to thrive in children and reduced bone mineralization in adolescents. PMID- 22076424 TI - Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. AB - Emerging evidence is revealing the different roles of steady laminar flow (s flow) and disturbed flow (d-flow) in the regulation of the vascular endothelium. s-flow is atheroprotective while d-flow creates an atheroprone environment. Most recently, we found unique atheroprone signals, which involve protein kinase C (PKC)zeta activation, elicited by d-flow. We and others have defined a novel role for PKCzeta as a shared mediator for tumor necrosis factor alpha (TNF alpha) and d-flow, which cause pro-inflammatory and pro-apoptotic events in endothelial cells (ECs) in the atheroprone environment. Under such conditions, ONOO(-) formation is increased in a d-flow-mediated PKCzeta-dependent manner. Here, we propose a new signaling pathway involving d-flow-induced EC inflammation via PKCzeta-ERK5 interaction-mediated downregulation of KLF2/eNOS stability, which leads to PKCzeta-mediated p53-SUMOylation and EC apoptosis. In addition, we highlight several mechanisms contributing to endothelial dysfunction, focusing on the relations between flow patterns and activation of reactive oxygen species generating enzymes. PMID- 22076427 TI - Bronchoepithelial expression of CXCR1 and CXCR2 does not facilitate transepithelial migration of neutrophils. AB - BACKGROUND: Neutrophilic airway inflammation is one of the key features of chronic obstructive pulmonary disease (COPD). The chemokine receptors 1 (CXCR1) and 2 (CXCR2) are expressed in the bronchial mucosa during chronic inflammation and might be of importance for transepithelial migration of neutrophils. OBJECTIVES: This study addressed the role of bronchoepithelial CXCR1 and CXCR2 expression with respect to transepithelial migration of neutrophils. METHODS: Primary bronchial epithelial cells (PBECs) derived from COPD patients and healthy controls as well as transiently CXCR1- and CXCR2-transfected Calu-6 cells were used for transepithelial migration assays of neutrophils under various conditions. Epithelial CXCR1 and CXCR2 expression was verified by means of flow cytometry. RESULTS: Transepithelial migration of neutrophils was significantly increased following lipopolysaccharide pretreatment of epithelial cells. Transient transfection of CXCR1 and CXCR2 neither augmented the transepithelial migration of neutrophils, nor did the selective blockade of CXCR1 and CXCR2 have any significant effect on neutrophilic transepithelial migration. In addition, no differences were found in PBECs and neutrophils derived from healthy controls and COPD patients. CONCLUSIONS: The data of the present study do not support the hypothesis that bronchoepithelial expression of CXCR1 and/or CXCR2 facilitate transepithelial migration of neutrophils. PMID- 22076428 TI - Extracellular fluid volume and glomerular filtration rate in 1878 healthy potential renal transplant donors: effects of age, gender, obesity and scaling. AB - Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects. METHODS: This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV. RESULTS: ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (<30 years) had higher GFR than young men but the reverse was recorded in the elderly (>65 years). There was no difference in GFR between obese (BMI>30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable. CONCLUSION: There are several significant differences in GFR and ECV between healthy men and women. PMID- 22076429 TI - What about the renal function during childhood of children born from dialysed mothers? AB - INTRODUCTION: Pregnancy during dialysis is a high-risk condition which is becoming more and more common. The renal outcome of children born from such pregnancies needs to be investigated since renal development may be affected (i.e. exposure to uraemic toxins, therapies, intermittent haemodynamic changes during sessions, prematurity, growth retardation). METHODS: We performed a single centre prospective global and renal evaluation (inulin clearance or 2009 Schwartz formula in children <4 years) in 10 children from 7 mothers who underwent haemodialysis during pregnancy. RESULTS: The median (range) age of mothers at the beginning of pregnancy was 30 (22-33) years, with maximal weekly haemodialysis duration of 18 (12-30) h. Systemic arterial hypertension was reported in 4 of 10 pregnancies, polyhydramnios in 3 and oligohydramnios in 1. The median (range) gestational age was 32 (29-39) weeks of gestation (WG). Seven children were born before 36 WG. The median (range) birth weight (BW) was 1735 (930-3430)g, and eight children had a BW <2500 g. One child had a PAX2 mutation requiring early renal transplantation and was thus excluded from further analysis. Even though glomerular filtration rate and blood pressure were normal in all other children, a significant urine albumin-to-creatinine ratio was found in three children and an increased urine beta-2-microglobulin concentration in an additional one, questioning the presence of an underlying silent reduction in nephron number. CONCLUSIONS: Despite the small number of patients, this pilot study highlights the potential risk of renal impairment in children born from dialysed mothers. Further studies are required but until then, careful monitoring of these children is important. PMID- 22076430 TI - Amiloride off-target effect inhibits podocyte urokinase receptor expression and reduces proteinuria. AB - The urokinase receptor (uPAR) and its soluble form play a key role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). The modification of uPAR pathological actions on podocytes will become an important task for the development of improved nephroprotective therapeutics. Here we show that podocyte uPAR expression can be reduced using amiloride. Amiloride has a significant role in the reduction of podocyte cell motility in vitro and proteinuria in mice. Amiloride inhibited the induction of uPAR protein and PLAUR messenger RNA (encoding uPAR) and with that it reduced uPAR-mediated beta3 integrin activation in lipopolysaccharide (LPS)-treated podocytes. Transwell migration assay and wound healing assay showed that directed and random podocyte motility of LPS treated podocytes were increased and substantially reduced by amiloride. The off target effect of amiloride was independent of its function as epithelial sodium channel blocker and different from triamterene. Amiloride was also effective in the LPS mouse model of transient proteinuria (LPS mice) and in the 5/6 nephrectomy rat FSGS model (NTX) by significantly inhibiting podocyte uPAR induction, reducing proteinuria. In addition, amiloride attenuated glomerulosclerosis, as determined by glomerulosclerotic index. Thus, our observations show that amiloride inhibits podocyte uPAR induction and reduces proteinuria in NTX rats and LPS mice. Given the pathological relevance of the uPAR-beta3 integrin signaling axis in FSGS, amiloride may be utilized in patients with FSGS. PMID- 22076431 TI - Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. AB - BACKGROUND: In patients with refractory steroid-sensitive nephrotic syndrome (SSNS), treatment with rituximab has shown encouraging results; however, long term follow-up data are not available. METHODS: We performed a retrospective analysis of 37 patients (25 boys) with steroid-dependent nephrotic syndrome who were treated with rituximab (375 mg/m(2) given weekly for one to four courses). Long-term follow-up data (>2 years, median 36, range 24-92.8 months) are available for 29 patients (12 boys). RESULTS: Twenty-six of 37 (70.3%) patients remained in remission after 12 months. Relapses occurred in 24 (64.8%) patients after a median of 9.6 (range 5.2-64.1) months. Time to first relapse was significantly shorter in patients receiving one or two compared to three or four initial infusions. In the 29 patients with long-term follow-up for >2 years, 12 (41%) patients remained in remission after the initial rituximab course for >24 months, 7 (24.1%) patients without further maintenance immunosuppression. Nineteen children received two to four repeated courses of rituximab increasing the total number of patients with long-term remission to 20 (69%), remission including 14 (48%) patients off immunosuppression. The proportion of patients with long-term remission was not related to the number of initial rituximab applications. No serious side effects were noted. CONCLUSION: Rituximab is an effective treatment option in the short- and long-term control of treatment refractory SSNS. Further controlled studies are needed to address optimal patient selection, dose and safety of rituximab infusions. PMID- 22076432 TI - Kidney and liver transplantation in patients with autosomal recessive polycystic kidney disease: a multicentric study. AB - BACKGROUND AND OBJECTIVES: In contrast to the improvement in our understanding of the pathogenesis and presentation of autosomal recessive polycystic kidney disease (ARPKD), data regarding the issue of kidney and liver transplantation in patients with ARPKD remain particularly scarce. Here, we report the results and outcome of renal and/or liver transplantation in a series of patients with ARPKD. METHODS: Fourteen ARPKD patients (age: 3-25 years) who underwent renal transplantation with or without liver transplantation were retrospectively identified in five French nephrology departments. The patients' medical charts were reviewed and relevant data were collected. RESULTS: The clinical and radiological presentation of the 14 patients was highly variable illustrating the heterogeneity of ARPKD. Six patients underwent kidney and/or liver transplantation in adulthood. First renal graft survival was 92, 78 and 14% at 1, 5 and 10 years after renal transplantation, respectively. Mortality rate was relatively high (3/14; 21%) in these young patients and was directly related to infectious complications (recurrent angiocholitis) of severe Caroli's disease (dilatation of intra- and/or extra-hepatic bile ducts), a typical feature of ARPKD. CONCLUSIONS: Our data suggest that ARPKD patients evaluated for renal transplantation should be carefully screened for severe Caroli's disease. Even though the limited number of patients included in our study precludes any definite recommendation, pre-emptive liver transplantation may be a therapeutic option in ARPKD patients with severe Caroli's disease evaluated for renal transplantation. PMID- 22076433 TI - Inhibition of the p38 MAPK pathway ameliorates renal fibrosis in an NPHP2 mouse model. AB - BACKGROUND: Nephronophthisis (NPHP), the most frequent genetic cause of end-stage kidney disease in children and young adults, is characterized by a variable number of renal cysts associated with cortical tubular atrophy and interstitial fibrosis. The p38 mitogen-activated protein kinase (MAPK) pathway is an important intracellular signaling pathway involved in the production of profibrotic mediators. The relationship between p38 MAPK and renal fibrosis in NPHP2 is unknown. METHODS: We administered a selective p38 MAPK inhibitor, FR167653, in a NPHP2 mouse model (inv/inv, invDeltaC mice) from 3 to 6 weeks old, and the kidneys were examined at 6 weeks of age. Phosphorylation of p38 MAPK (p-p38 MAPK) protein levels, the degree of renal fibrosis, messenger RNA (mRNA) levels for extracellular matrix genes and mRNA levels for transforming growth factor in the kidneys were studied. Effect of an extracellular signal-regulated protein kinase (ERK) kinase (MEK) inhibitor on renal fibrosis was also evaluated. RESULTS: Expression of extracellular matrix genes and p-p38 MAPK were increased in the NPHP2 mouse model kidney. FR167653 successfully decreased p-p38 MAPK levels, the degree of fibrosis and extracellular matrix gene expressions. However, the FR167653 did not prevent cyst expansion, abnormal cell proliferation and acceleration of apoptosis and did not influence ERK activation. In contrast, MEK inhibition reduced both cyst expansion and fibrosis without affecting p38 MAPK activation. CONCLUSIONS: These results suggest that inhibition of p38 MAPK reduced renal fibrosis but not cyst expansion, cell proliferation and apoptosis in NPHP2 model mice. Our results suggest that p38 MAPK and ERK signaling pathways independently affect renal fibrosis in inv mutant mice. PMID- 22076434 TI - High-fat diet-induced renal cell apoptosis and oxidative stress in spontaneously hypertensive rat are ameliorated by fenofibrate through the PPARalpha-FoxO3a-PGC 1alpha pathway. AB - BACKGROUND: The peroxisome proliferator-activated receptor-alpha (PPARalpha) is a lipid-sensing transcriptional factor that has a role in gluco-oxidative stress and lipotoxicity. Forkhead box O (FoxO)s and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha are also known to regulate cell metabolism, cell cycle arrest, apoptosis and oxidative stress during stressful conditions. We evaluated whether PPARalpha-FoxOs-PGC-1alpha signaling in overfed spontaneously hypertensive rats (SHR) has a protective role in the kidney. METHODS: Male SHR and Wistar-Kyoto rats (WKY) fed a high-fat diet (HFD) received treatment with fenofibrate, PPARalpha agonist or tempol, antioxidants for 12 weeks and were evaluated about the PPARalpha-FoxOs-PGC-1alpha pathway. RESULTS: The SHRs with an HFD had an elevated systolic pressure, plasma insulin, free fatty acid (FFA) and triglyceride (TGs) levels, and they had induced glucose intolerance as well as albuminuria, glomerular expansion and renal inflammation. An HFD caused the accumulation of intra-renal FFA and TGs and this was related to a decrease in the PPARalpha expression, the activation of phosphatidylinositol 3 kinase (PI3K)-Akt, phosphorylation of FoxO3a and decreases in the PGC-1alpha and estrogen-related receptor (ERR)-1alpha expressions, which suppressed the superoxide dismutase (SOD2) and Bcl-2 expressions and led to increases in oxidative stress and the number of apoptotic renal cells. Interestingly, administering fenofibrate or tempol to the HFD-induced SHRs reversed all of the renal phenotypes by increasing the PPARalpha expression with concomitant inactivation of the PI3K-Akt pathway, dephosphorylation of FoxO3a and activation of PGC-1alpha-ERR-1alpha signaling, and this all resulted in ameliorating the oxidative stress and apoptotic cell death. CONCLUSION: Our results demonstrated that PPARalpha agonists or antioxidants are associated with improvement of the circulating FFA and TGs levels and this prevents HFD-induced renal lipotoxicity and hypertension by the activation of PPARalpha and its downstream signals of both FoxO3a and PGC-1alpha. PMID- 22076435 TI - Proteomic analysis reveals overexpression of moesin and cytokeratin 17 proteins in colorectal carcinoma. AB - The study of tumor biomarkers was gradually facilitated by the adoption of proteomic strategies due to less invasiveness and higher sensitivity. Colorectal cancer is one of the most commonly occurring cancers worldwide and its incidence has markedly increased in Korea. While the adoption of proteomic strategies facilitated the study of tumor biomarkers, to date, no common agreement has been derived from proteomic investigations regarding tumor markers of colorectal cancer. This study was designed to find molecules differentially expressed in colorectal cancer compared to non-tumor mucosa. Four colorectal adenocarcinoma and corresponding non-tumor tissue samples were analyzed to find previously unknown proteins via two-dimensional electrophoresis and MALDI-TOF/MS spectrometry. Western blot assays and tissue microarray (TMA) immunohistochemistry were performed to validate the identified proteins. Among the twelve up-regulated and one down-regulated proteins identified, moesin, cytokeratin (KRT) 17 and carbonic anhydrase I were validated by western blot analysis and/or immunohistochemistry. On immunohistochemistry, both moesin and KRT17 demonstrated a tendency of increased expression as pT stage advanced. Both moesin and KRT17 were not expressed in normal colorectal epithelium. These two proteins may play a role in cancer invasion and/or metastasis in colorectal carcinoma, and could be candidate biomarkers for the diagnosis and prognosis of colorectal cancer. PMID- 22076436 TI - CCL21 modulates the migration of NSCL cancer by changing the concentration of intracellular Ca2+. AB - Recurrence and metastasis are the major factors associated with the poor prognosis of non-small cell lung cancer (NSCLC). It has been shown that multiple chemokines and their receptors are related to the progression and metastasis of NSCLC. The aim of this study was to conduct an investigation into whether CCL21 and its receptor, CCR7, play a role in NSCLC invasion and metastasis. We used Western blotting, immunocytochemistry and flow cytometry to detect CCR7 protein expression in four NSCLC cell lines EKVX, HOP-62, NCI-H23 and Slu-01; and we conducted a cell migration experiment to observe the pseudopodia formation and mobility of the lung cancer cells. The concentration of intracellular calcium was measured by fluorescence microscopy. CCR7 protein was positively expressed in the four NSCLC cell lines EKVX, HOP-62, NCI-H23 and Slu-01. Following CCL21 stimulation, obvious pseudopodia formation of lung cancer cells was observed. The cell migration experiment showed that following incubation with CCL21, the number of EKVX cells which passed through the polycarbonate micro-porous filter membranes also increased to an obvious extent. After CCL21 incubation, the intracellular Ca2+ level of the EKVX cells increased to an obvious extent. Chemokine CCL21 facilitates the migration of lung cancer by changing the concentration of intracellular Ca2+. The CCL21-CCR7 axis may play an important role in NSCLC invasion and metastasis. It may also be a potential target for NSCLC therapy or for prevention of the recurrence and metastasis of NSCLC. PMID- 22076437 TI - Methods to limit attrition in longitudinal comparative effectiveness trials: lessons from the Lithium Treatment - Moderate dose Use Study (LiTMUS) for bipolar disorder. AB - BACKGROUND: High attrition rates, which occur frequently in longitudinal clinical trials of interventions for bipolar disorder, limit the interpretation of results. PURPOSE: The aim of this article is to present design approaches that limited attrition in the Lithium Treatment - Moderate dose Use Study (LiTMUS) for bipolar disorder. METHODS: LiTMUS was a 6-month randomized, longitudinal multisite comparative effectiveness trial that enrolled bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium; other treatments needed for mood stabilization were administered in a guideline-informed, empirically supported, and personalized fashion to participants in both treatment arms. RESULTS: Components of the study design that may have contributed to low attrition (16%) among 283 participants randomized included the use of (1) an intent-to-treat design, (2) a randomized adjunctive single-blind design, (3) participant reimbursement, (4) assessment of intent to attend the next study visit (included a discussion of attendance obstacles when intention was low), (5) quality care with limited participant burden, and (6) target windows for study visits. LIMITATIONS: The relationships between attrition and effectiveness and tolerability of treatment have not been analyzed yet. CONCLUSIONS: These components of the LiTMUS design may have limited attrition and may inform the design of future randomized comparative effectiveness trials among similar patients and those from other difficult-to-follow populations. PMID- 22076439 TI - ErbB4 modulates tubular cell polarity and lumen diameter during kidney development. AB - ErbB4 receptor tyrosine kinase contributes to the development of the heart, the central nervous system, and the lactating mammary gland, but whether it has a role in the development of the kidney epithelium is unknown. Here, we found that expression of Erbb4 isoforms JM-a CYT-1 and JM-a CYT-2 was first detectable around embryonic day 13 in the mouse, mainly in the collecting ducts and both the proximal and distal tubules. In vitro, overexpression of a relevant ErbB4 isoform promoted proliferation and disturbed polarization of kidney epithelial cells when cultured as three-dimensional structures. We examined ErbB4 function in developing kidney tubules in vivo with Pax8-Cre-mediated conditional overexpression of Rosa26 locus-targeted ERBB4 and with conditional Erbb4 knock out mice. The Pax8-Cre-driven ERBB4 overexpression enhanced proliferation in the collecting ducts, reduced the size of epithelial duct lumens, and promoted formation of cortical tubular cysts. These defects were associated with changes in the subcellular distribution of markers of epithelial cell polarity. Similarly, the Pax8-Cre-mediated Erbb4 knock-out mice manifested dysfunctional kidneys with larger duct lumens and epithelial cell mispolarization. Taken together, these data suggest that ErbB4 signaling modulates proliferation and polarization, cellular functions critical for the development of epithelial ducts in the kidney. PMID- 22076440 TI - Selective neuroprotective effects of the S18Y polymorphic variant of UCH-L1 in the dopaminergic system. AB - Genetic studies have implicated the neuronal ubiquitin C-terminal hydrolase (UCH) protein UCH-L1 in Parkinson's disease (PD) pathogenesis. Moreover, the function of UCH-L1 may be lost in the brains of PD and Alzheimer's disease patients. We have previously reported that the UCH-L1 polymorphic variant S18Y, potentially protective against PD in population studies, demonstrates specific antioxidant functions in cell culture. Albeit genetic, biochemical and neuropathological data support an association between UCH-L1, PD, synaptic degeneration and oxidative stress, the relationship between the dopaminergic system and UCH-L1 status remains obscure. In the current study, we have examined the dopaminergic system of mice lacking endogenous UCH-L1 protein (gracile axonal dystrophy mice). Our findings show that the lack of wild-type (WT) UCH-L1 does not influence to any significant degree the dopaminergic system at baseline or following injections of the neurotoxin methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, using a novel intrastriatal adenoviral injection protocol, we have found that mouse nigral neurons retrogradely transduced with S18Y UCH-L1, but not the WT protein, are significantly protected against MPTP toxicity. Overall, these data provide evidence for an antioxidant and neuroprotective effect of the S18Y variant of UCH-L1, but not of the WT protein, in the dopaminergic system, and may have implications for the pathogenesis of PD or related neurodegenerative conditions, in which oxidative stress might play a role. PMID- 22076441 TI - A glial origin for periventricular nodular heterotopia caused by impaired expression of Filamin-A. AB - Periventricular nodular heterotopia (PH) is a human brain malformation caused by defective neuronal migration that results in ectopic neuronal nodules lining the lateral ventricles beneath a normal appearing cortex. Most affected patients have seizures and their cognitive level varies from normal to severely impaired. Mutations in the Filamin-A (or FLNA) gene are the main cause of PH, but the underlying pathological mechanism remains unknown. Although two FlnA knockout mouse strains have been generated, none of them showed the presence of ectopic nodules. To recapitulate the loss of FlnA function in the developing rat brain, we used an in utero RNA interference-mediated knockdown approach and successfully reproduced a PH phenotype in rats comparable with that observed in human patients. In FlnA-knockdown rats, we report that PH results from a disruption of the polarized radial glial scaffold in the ventricular zone altering progression of neural progenitors through the cell cycle and impairing migration of neurons into the cortical plate. Similar alterations of radial glia are observed in human PH brains of a 35-week fetus and a 3-month-old child, harboring distinct FLNA mutations not previously reported. Finally, juvenile FlnA-knockdown rats are highly susceptible to seizures, confirming the reliability of this novel animal model of PH. Our findings suggest that the disorganization of radial glia is the leading cause of PH pathogenesis associated with FLNA mutations. Rattus norvegicus FlnA mRNA (GenBank accession number FJ416060). PMID- 22076443 TI - Refinement of the associations between risk of colorectal cancer and polymorphisms on chromosomes 1q41 and 12q13.13. AB - In genome-wide association studies (GWASs) of colorectal cancer, we have identified two genomic regions in which pairs of tagging-single nucleotide polymorphisms (tagSNPs) are associated with disease; these comprise chromosomes 1q41 (rs6691170, rs6687758) and 12q13.13 (rs7163702, rs11169552). We investigated these regions further, aiming to determine whether they contain more than one independent association signal and/or to identify the SNPs most strongly associated with disease. Genotyping of additional sample sets at the original tagSNPs showed that, for both regions, the two tagSNPs were unlikely to identify a single haplotype on which the functional variation lay. Conversely, one of the pair of SNPs did not fully capture the association signal in each region. We therefore undertook more detailed analyses, using imputation, logistic regression, genealogical analysis using the GENECLUSTER program and haplotype analysis. In the 1q41 region, the SNP rs11118883 emerged as a strong candidate based on all these analyses, sufficient to account for the signals at both rs6691170 and rs6687758. rs11118883 lies within a region with strong evidence of transcriptional regulatory activity and has been associated with expression of PDGFRB mRNA. For 12q13.13, a complex situation was found: SNP rs7972465 showed stronger association than either rs11169552 or rs7136702, and GENECLUSTER found no good evidence for a two-SNP model. However, logistic regression and haplotype analyses supported a two-SNP model, in which a signal at the SNP rs706793 was added to that at rs11169552. Post-GWAS fine-mapping studies are challenging, but the use of multiple tools can assist in identifying candidate functional variants in at least some cases. PMID- 22076444 TI - Brain activation during oral exercises used for dysphagia rehabilitation in healthy human subjects: a functional magnetic resonance imaging study. AB - Oral exercises, including tongue, lip, and jaw movements, are commonly used in clinical practice as training to improve oral and pharyngeal swallowing in dysphagia patients. These rehabilitation exercises are believed to affect the peripheral and central nervous system at various levels. However, few studies have examined healthy subjects' brain activity while performing oral exercises used in dysphagia rehabilitation. The current study sought to measure brain activation during oral exercises in healthy subjects using functional magnetic resonance imaging (fMRI). Lip-pursing and lip-stretching, tongue protrusion, lateral tongue movement, and oral ball-rolling were selected as tongue and lip exercise tasks. The tasks were performed by eight healthy subjects, and the fMRI data were submitted to conjunction analyses. The results confirmed that head movements during all tasks exhibited translation of <1.0 mm and rotation of <1.0 degrees in x, y, and z coordinates. We found several clear regions of increased brain activity during all four oral exercises. Commonly activated regions during tongue and lip exercises included the precentral gyrus and cerebellum. Brain activation during ball-rolling was more extensive and stronger compared to the other three oral exercises. PMID- 22076445 TI - Cell phone use among homeless youth: potential for new health interventions and research. AB - Cell phone use has become nearly ubiquitous among adolescents in the United States. Despite the potential for cell phones to facilitate intervention, research, and care for homeless youth, no data exists to date on cell phone use among this population. In 2009, a survey of cell phone use was conducted among a non-probability sample of 169 homeless youth in Los Angeles, CA. Levels of ownership and use, instrumental uses (connecting to case workers, employers) and patterns of connecting to various network types were assessed (family, home-based peers, street-based peers). Differences in socio-demographic characteristics and cell phone ownership were assessed via t test and chi-square statistics. Sixty two percent of homeless youth own a cell phone; 40% have a working phone. Seventeen percent used their phone to call a case manager, 36% to call either a potential or current employer. Fifty-one percent of youth connected with home based peers on the phone and 41% connected to parents. Cell phones present new opportunities for intervention research, connecting homeless youth to family and home-based peers who can be sources of social support in times of need. Moreover, cell phones provide researchers and providers with new avenues to maintain connections with these highly transient youth. PMID- 22076442 TI - A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations. AB - A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P(MH)= 1.92 * 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P(MH)= 4.84 * 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P(chi2) = 2.82 * 10(-4) OR = 1.34). After performing overall pooled analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P(MH)= 2.82 * 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis. PMID- 22076446 TI - Identification of a methylation hotspot in the death receptor Fas/CD95 in bladder cancer. AB - We characterized Fas immunoreactivity, functionality and its role in the response to mitomycin-C (MMC) chemotherapy in vitro in cell lines and in vivo in bladder washings from 23 transitional cell carcinoma of the bladder (TCCB) patients, harvested prior to and during MMC intravesical treatment. Having established the importance of functional Fas, we investigated the methylation and exon 9 mutation as mechanisms of Fas silencing in TCCB. For the first time, we report p53 up regulation in 9/14 and Fas up-regulation in 7/9 TCCB patients during intravesical MMC treatment. Fas immunoreactivity was strong in the TCCB cell line T24 and in 17/20 (85%) tumor samples from patients with advanced TCCB. T24 and HT1376 cells were resistant to MMC and recombinant Fas ligand, whilst RT4 cells were responsive to Fas ligand and MMC. Using RT4 cells as a model, siRNA targeting p53 significantly reduced MMC-induced p53 and Fas up-regulation and stable DN-FADD transfection decreased MMC-induced apoptosis, suggesting that functional Fas enhances chemotherapy responses in a p53-dependent manner. In HT1376 cells, 5-aza 2-deoxycytidine (12 uM) induced Fas immunoreactivity and reversed methylation at CpG site -548 within the Fas promoter. This site was methylated in 13/24 (54%) TCCB patient samples assessed using Methylation-Specific Polymerase Chain Reaction. There was no methylation at either the p53 enhancer region within the first intron or at the SP-1 binding region in the promoter and no mutation within exon 9 in tumor DNA extracted from 38 patients. Methylation at CpG site -548 is a potential target for demethylating drugs. PMID- 22076447 TI - The pharmacokinetic-pharmacodynamic assessment of the hypotensive effect after coadministration of losartan and hydrochlorothiazide in spontaneously hypertensive rats. AB - The interactive hypotensive effect of the combination treatment of losartan (LOS) and hydrochlorothiazide (HCTZ) was assessed using a pharmacokinetic pharmacodynamic (PK-PD) model in spontaneously hypertensive rats. Intravenous coadministration of these drugs showed a prolonged and enhanced time-course of the hypotensive effect. A population PK analysis revealed the delayed elimination of LOS after coadministration. The time-course of the plasma renin activity (PRA) was measured, and showed a more continuative time profile after coadministration compared with the administration of LOS alone. An indirect response model was applied to describe the relationship between the PK of LOS and the PRA profile, and the E(max) value for the increase of the PRA by LOS was increased with the dose of HCTZ. Blood pressure was linked to the PRA through an effect compartment. The model successfully described the relationship between the doses of LOS and HCTZ and their interactive hypotensive effect. These results indicate that the interaction for blood pressure in the combination treatment of LOS and HCTZ can be estimated using the doses of the drugs and the PRA-mediated PK-PD model. PMID- 22076448 TI - Polycyclic aromatic hydrocarbons activate CYP3A4 gene transcription through human pregnane X receptor. AB - Aryl hydrocarbon receptor (AhR) activators have been shown to induce members of the cytochrome P450 (P450) 1 family. Here we demonstrate that the AhR activators induce CYP3A4 through human pregnane X receptor (PXR). AhR activators, polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased CYP3A4 reporter activity and CYP3A4 mRNA expression in HepG2 cells. The CYP3A4 reporter activity was also increased by treatment with cigarette tar. The increased CYP3A4 reporter activity was clearly knocked down by the introduction of human PXR-small interfering RNA, but not by that of human AhR-small interfering RNA. The CYP3A4 reporter activity enhanced by overexpression of human PXR was further increased by treatment with PAHs and TCDD as well as by treatment with rifampicin. These results suggest that PAHs contained in cigarette smoke induce CYP3A4 in human liver. PMID- 22076449 TI - Relation between bevacizumab dose intensity and high-grade glioma survival: a retrospective study in two large cohorts. AB - Bevacizumab is one of the rare drugs that could improve high-grade glioma outcome after failure of chemoradiotherapy. However, to date, there is no biomarker predictive for efficacy of bevacizumab therapy in terms of survival improvement for patients with high-grade glioma. We performed a retrospective analysis of clinical factors associated with patient survival using a training cohort of 110 consecutive patients treated with bevacizumab for recurrent high-grade glioma and an independent validation cohort of 109 patients. In the training cohort, 110 consecutive patients received bevacizumab-based therapy. The number of chemotherapy cycles delivered was 1,411. Median follow-up was 12 months. Thirty four patients (31%) had objective partial response and 24% had stable disease on magnetic resonance imaging evaluation. Median progression-free survival (PFS) and overall survival (OS) were 4.3 and 9.2 months, respectively. On univariate analysis, among classical prognosis factors, only Karnofsky status >=70% was associated with improved outcome. Surprisingly, patients with low bevacizumab dose intensity (<5 mg/kg/week) had better PFS (12 vs. 2 months, P < 0.0001) and OS (16 vs. 6 months, P = 0.0002). On multivariate analysis, low bevacizumab dose intensity was the most significant independent prognostic factor of survival. Analysis of the validation cohort yielded similar results, externally validating this observation. This large retrospective study using two independent cohorts of high-grade glioma suggests that the currently recommended dosage of bevacizumab (5 mg/kg/week) is not optimal. Further prospective randomized trials using lower dosages are warranted. PMID- 22076450 TI - Sporadic CNS hemangioblastomatosis, response to sunitinib and secondary polycythemia. PMID- 22076451 TI - Managing burn emergencies. AB - Nursing interventions in the first crucial hours after a burn injury can improve the patient's chances of survival and a good recovery. This article describes how to rapidly assess and intervene, in the field and in the hospital. PMID- 22076454 TI - The etiology of thrombocytopenia. AB - Hemostasis depends on an adequate number of well-functioning platelets in the circulating blood; decreasing platelet levels raise the risk for bleeding. Thrombocytopenia is a laboratory finding, not a diagnosis, and once identified, a detailed history, physical examination, and further laboratory tests are used to establish an etiology. This article reviews the assessment, diagnosis, and treatment of thrombocytopenia. PMID- 22076455 TI - Caring for the woman with migraine headaches. AB - About 16% of American women experience migraine headaches. These debilitating headaches cause lost time from family, social activities, and work. Although migraines are thought to be a result of shifting menstrual and perimenopausal hormones, a physiologic connection has not been well established. This article approaches premenstrual and perimenopausal migraine headaches from a chronic disease perspective, focusing on self-care and the use of prescription and nonprescription therapies. Implications for practice and future research also are discussed. PMID- 22076456 TI - Ground zero: building a cardiac surgery program. AB - More and more community hospitals are opening cardiovascular surgery programs to provide a broader spectrum of services closer to home. This article leads the reader through one hospital's experience in opening a new heart center and highlights the philosophy, triaging of issues, and staff preparation needed to achieve successful patient outcomes. Our case study can serve as a guide for other hospitals as they take on the challenge of opening new programs. PMID- 22076457 TI - How a work group facilitator can help units reach goals. AB - Nurse managers have many demands on their time, and many unit and organizational goals to meet. This article describes skills for facilitating work groups and reaching goals by focusing others' talents. PMID- 22076459 TI - Critical care nursing orientation in the rural community hospital. AB - Hospitals of all sizes should provide an orientation for their newly hired critical care nurses-but when the hospital is a rural community facility, resources for such programs may be in especially short supply. In this article, we describe how our hospital overcame staffing and funding shortages to create a successful, collaborative orientation program for its critical care nurses. PMID- 22076460 TI - Bed rest after percutaneous transluminal coronary angioplasty: how much is enough? AB - This literature review explores current research on the amount of bed rest necessary after PTCA. Because of the wide variation in postprocedure bed rest requirements, more research is needed in this area to help advanced practice nurses better care for post-PTCA patients by adapting nursing protocols to reflect evidence-based practice. PMID- 22076461 TI - Education: the key to retention. PMID- 22076462 TI - Neural control of olfaction and tentacle movements by serotonin and dopamine in terrestrial snail. AB - We investigated the role of serotonin (5HT) and dopamine (DA) in the regulation of olfactory system function and odor-evoked tentacle movements in the snail Helix. Preparations of the posterior tentacle (including sensory pad, tentacular ganglion and olfactory nerve) or central ganglia with attached posterior tentacles were exposed to cineole odorant and the evoked responses were affected by prior application of 5HT or DA or their precursors 5-hydroxytryptophan (5HTP) and L: -DOPA, respectively. 5HT applications decreased cineole-evoked responses recorded in the olfactory nerve and hyperpolarized the identified tentacle retractor muscle motoneuron MtC3, while DA applications led to the opposite changes. 5HTP and L: -DOPA modified MtC3 activity comparable to 5HT and DA action. DA was also found to decrease the amplitude of spontaneous local field potential oscillations in the procerebrum, a central olfactory structure. In vivo studies demonstrated that injection of 5HTP in freely moving snails reduced the tentacle withdrawal response to aversive ethyl acetate odorant, whereas the injection of L: -DOPA increased responses to "neutral" cineole and aversive ethyl acetate odorants. Our data suggest that 5HT and DA affect the peripheral (sensory epithelium and tentacular ganglion), the central (procerebrum), and the single motor neuron (withdrawal motoneuron MtC3) level of the snail's nervous system. PMID- 22076463 TI - Venous thromboembolism in patients with essential thrombocythemia and polycythemia vera. AB - Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPNs), which generally follow a benign and indolent clinical course. However, venous thromboses are common and constitute the main cause of morbidity and mortality. The discovery of the JAK2V617F mutation and other biomarkers has advanced our understanding of these diseases. There is a strong association between the presence of the JAK2V617F mutation and the development of thrombosis in ET. If venous thrombosis presents with unusual manifestations, the diagnosis of a MPN, such as PV or ET, should be part of the differentials. Treatment of venous thrombosis in MPN follows the same principle as in other patients with venous thrombosis, but careful attention to primary and secondary prophylaxis in addition to heparin-induced thrombocytopenia should be given. Cytoreductive therapy is indicated in high-risk subgroups of PV and ET patients, and alternative therapeutic agents have different effects on risk of venous thrombosis. New therapeutic approaches are emerging, and JAK2 inhibitors, histone deacetylase inhibitors and next-generation anticoagulants are in various stages of clinical development for the treatment of MPN, but their exact role in thrombosis prevention and treatment remains unclear. PMID- 22076464 TI - Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia. AB - Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells. The etiology of ALL is believed to be multifactorial and likely to involve an interplay of environmental and genetic variables. We performed a genome-wide association study of 355 750 single-nucleotide polymorphisms (SNPs) in 474 controls and 419 childhood ALL cases characterized by a t(12;21)(p13;q22) - the most common chromosomal translocation observed in childhood ALL - which leads to an ETV6-RUNX1 gene fusion. The eight most strongly associated SNPs were followed up in 951 ETV6-RUNX1-positive cases and 3061 controls from Germany/Austria and Italy, respectively. We identified a novel, genome-wide significant risk locus at 3q28 (TP63, rs17505102, P(CMH)=8.94 * 10(-9), OR=0.65). The separate analysis of the combined German/Austrian sample only, revealed additional genome-wide significant associations at 11q11 (OR8U8, rs1945213, P=9.14 * 10(-11), OR=0.69) and 8p21.3 (near INTS10, rs920590, P=6.12 * 10(-9), OR=1.36). These associations and another association at 11p11.2 (PTPRJ, rs3942852, P=4.95 * 10(-7), OR=0.72) remained significant in the German/Austrian replication panel after correction for multiple testing. Our findings demonstrate that germline genetic variation can specifically contribute to the risk of ETV6-RUNX1-positive childhood ALL. The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis. PMID- 22076465 TI - Glycolysis inhibition targets Mcl-1 to restore sensitivity of lymphoma cells to ABT-737-induced apoptosis. PMID- 22076466 TI - Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. AB - Nilotinib (Tasigna) is a potent and selective BCR-ABL inhibitor approved for use in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CML-CP) and in patients with CML-CP and accelerated phase (CML-AP) who are resistant to or intolerant of imatinib. Patients with CML-AP (N = 137) with at least 24 months of follow-up or who discontinued early were evaluated to determine the efficacy and tolerability of nilotinib. The majority (55%) of patients achieved a confirmed hematologic response, and 31% attained a confirmed complete hematologic response on nilotinib treatment. Overall, 32% of patients achieved major cytogenetic responses (MCyR), with most being complete cytogenetic responses. Responses were durable, with 66% of patients maintaining MCyR at 24 months. The estimated overall and progression-free survival rates at 24 months were 70% and 33%, respectively. Grade 3/4 neutropenia and thrombocytopenia were each observed in 42% of patients. Non-hematologic adverse events were mostly mild to moderate; the safety profile of nilotinib has not changed with longer follow up. In all, 20 (15%) patients remained on study at data cutoff. In summary, nilotinib has a manageable safety profile, and can provide favorable long-term outcomes in the pretreated CML-AP patient population for whom treatment options are limited. PMID- 22076467 TI - Human skeletal muscle stem cell antiinflammatory activity ameliorates clinical outcome in amyotrophic lateral sclerosis models. AB - Mesenchymal stem cell (MSC) therapy is considered one of the most promising approaches for treating different neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). We previously characterized a subpopulation of human skeletal muscle-derived stem cells (SkmSCs) with MSC-like characteristics that differentiate into the neurogenic lineage in vitro. In the present study, we evaluated the SkmSC therapeutic effects in the most characterized model of spontaneous motor neuron degeneration, the Wobbler (Wr) mouse. Before evaluating the therapeutic efficacy in the Wr mouse, we followed the route of Skm-SCs at different times after intracerebroventricular injection. Two exogenous tracers, superparamagnetic iron oxide (SPIO) nanoparticles and Hoechst 33258, were used for the in vivo and ex vivo tracking of SkmSCs. We found that the loading of both Hoechst and SPIO was not toxic and efficiently labeled SkmSCs. The magnetic resonance imaging (MRI) system 7 Tesla allowed us to localize transplanted SkmSCs along the whole ventricular system up to 18 wks after injection. The ex vivo Hoechst 33258 visualization confirmed the in vivo results obtained by MRI analyses. Behavioral observations revealed a fast and sustained improvement of motor efficacy in SkmSC-treated Wr mice associated with a relevant protection of functional neuromuscular junctions. Moreover, we found that in SkmSC-treated Wr mice, a significant increase of important human antiinflammatory cytokines occurred. This evidence is in accordance with previous findings showing the bystander effect of stem cell transplantation in neurodegenerative disorders and further strengthens the hypothesis of the possible link between inflammation, cytotoxicity and ALS. PMID- 22076468 TI - High mobility group box protein 1 (HMGB1)-partner molecule complexes enhance cytokine production by signaling through the partner molecule receptor. AB - The nuclear protein high mobility group box protein 1 (HMGB1) promotes inflammation upon extracellular release. HMGB1 induces proinflammatory cytokine production in macrophages via Toll-like receptor (TLR)-4 signaling in a redox dependent fashion. Independent of its redox state and endogenous cytokine inducing ability, HMGB1 can form highly immunostimulatory complexes by interaction with certain proinflammatory mediators. Such complexes have the ability to enhance the induced immune response up to 100-fold, compared with induction by the ligand alone. To clarify the mechanisms for these strong synergistic effects, we studied receptor requirements. Interleukin (IL)-6 production was assessed in supernatants from cultured peritoneal macrophages from mice each deficient in one of the HMGB1 receptors (receptor for advanced glycation end products [RAGE], TLR2 or TLR4) or from wild-type controls. The cultures were stimulated with the TLR4 ligand lipopolysaccaride (LPS), the TLR2 ligand Pam3CysSerLys4 (Pam3CSK4), noninflammatory HMGB1 or each TLR ligand in complex with noninflammatory HMGB1. The activity of the HMGB1-TLR ligand complexes relied on engagement of the same receptor as for the noncomplexed TLR ligand, since HMGB1-LPS complexes used TLR4 and HMGB1-Pam3CSK4 complexes used TLR2. Deletion of any of the intracellular adaptor molecules used by TLR2 (myeloid differentiation factor-88 [MyD88], TIR domain-containing adaptor protein [TIRAP]) or TLR4 (MyD88, TIRAP, TIR domain-containing adaptor-inducing interferon beta [TRIF], TRIF-related adaptor molecule [TRAM]) had similar effects on HMGB1 complex activation compared with noncomplexed LPS or Pam3CSK4. This result implies that the enhancing effects of HMGB1-partner molecule complexes are not regulated by the induction of additional signaling cascades. Elucidating HMGB1 receptor usage in processes where HMGB1 acts alone or in complex with other molecules is essential for the understanding of basic HMGB1 biology and for designing HMGB1-targeted therapies. PMID- 22076469 TI - Postnatal rosiglitazone administration to neonatal rat pups does not alter the young adult metabolic phenotype. AB - BACKGROUND: Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, significantly enhances lung maturation without affecting blood biochemical and metabolic profiles in the newborn period. However, whether this exposure to RGZ in neonatal life alters the adult metabolic phenotype is not known. OBJECTIVE: To determine the effects of early postnatal administration of RGZ on the young adult metabolic phenotype. METHODS: Newborn rat pups were administered either saline or RGZ for the first 7 days of life. At 11-14 weeks, glucose and insulin tolerance tests and deuterium labeling were performed. Blood and tissues were analyzed for various metabolic parameters. RESULTS: Overall, there was no effect of early postnatal RGZ administration on young adult body weight, glucose and insulin tolerance, plasma cholesterol and triglyceride profiles, insulin, glucagon, cardiac troponin, fatty acid synthesis, or tissue adipogenic differentiation. CONCLUSIONS: Treatment with RGZ in early neonatal life does not alter later developmental metabolic programming or lead to an altered metabolic phenotype in the young adult, further re-enforcing the safety of PPARgamma agonists as a novel lung-protective strategy. PMID- 22076470 TI - Improving molecular docking through eHiTS' tunable scoring function. AB - We present three complementary approaches for score-tuning that improve docking performance in pose prediction, virtual screening and binding affinity assessment. The methodology utilizes experimental data to customize the scoring function for the system of interest considering the specific docking scenario. The tuning approach, which has been implemented as an automated utility in eHiTS, is introduced as a solution to one of the conundrums of the molecular docking paradigm, namely, the lack of a universally well performing scoring function. The accuracy of scoring functions has been shown to be generally system-dependent, and particularly lacking for binding energy and bio-activity predictions. In the proposed approach, pose and energy predictions are enhanced by adjusting the relative weights of the eHiTS energy terms to improve score-RMSD or score affinity correlations. In a virtual screening context ligand-based similarity is used to rescale the docking score such that better enrichment factors are achieved. We discuss the algorithmic details of the methods, and demonstrate the effects of score tuning on a variety of targets, including CDK2, BACE1 and neuraminidase, as well as on the popular benchmarks--the Directory of Useful Decoys and the PDBBind database. PMID- 22076471 TI - Molecular dynamics of Mycobacterium tuberculosis KasA: implications for inhibitor and substrate binding and consequences for drug design. AB - Inhibition of the production of fatty acids as essential components of the mycobacterial cell wall has been an established way of fighting tuberculosis for decades. However, increasing resistances and an outdated medical treatment call for the validation of new targets involved in this crucial pathway. In this regard, the beta-ketoacyl ACP synthase KasA is a promising enzyme. In this study, three molecular dynamics simulations based on the wildtype crystal structures of inhibitor bound and unbound KasA were performed in order to investigate the flexibility and conformational space of this target. We present an exhaustive analysis of the binding-site flexibility and representative pocket conformations that may serve as new starting points for structure-based drug design. We also revealed a mechanism which may account for the comparatively low binding affinity of thiolactomycin. Furthermore, we examined the behavior of water molecules within the binding pocket and provide recommendations how to handle them in the drug design process. Finally, we analyzed the dynamics of a channel that accommodates the long-chain fatty acid substrates and, thereby, propose a mechanism of substrate access to this channel and how products are most likely released. PMID- 22076472 TI - Robotic extravesical anti-reflux operations in complex cases: technical considerations and preliminary results. AB - OBJECTIVES: To evaluate technical aspects and outcome of robotic laparoscopic extravesical anti-reflux surgery in the treatment of high-grade vesicoureteral reflux (VUR) with associated complicating conditions. MATERIALS AND METHODS: Retrospective database and chart reviews were performed to identify a subgroup of patients with high-grade VUR who underwent robot-assisted anti-reflux surgery using the extravesical Lich-Gregoir repair and who additionally had preoperatively known complicating factors. Five such patients were operated on from 2005 to 2009. All had bilateral VUR, bladder dysfunction, breakthrough infections, renal scarring or at least one of the following complicating factors: posterior urethral valve bladders, duplex systems or para-ostial diverticula. Outcome and surgical aspects were assessed. RESULTS: At follow-up 9 of 10 ureters were free of reflux and diverticulae had disappeared completely. No lasting urinary retentions occurred but two boys needed reinsertion of a catheter for 24 h after surgery. No further complications were noted. There were no signs of obstruction, infections did not persist and there was no negative effect on bladder function. Dissection of para-ostial diverticula seemed the only additional technical challenge. CONCLUSIONS: Robot-assisted extravesical anti reflux surgery seems a promising technique in the operative management of this unfavorable subset of patients. Reflux cure rate is higher than expected using injection therapy and at the same time morbidity seems lower than with open surgery. Further experience is needed to confirm these first impressions. PMID- 22076473 TI - PI-PLCbeta1 gene copy number alterations in breast cancer. AB - Deregulation of signal transduction pathways frequently confers selective biological advantages to tumors. Phosphoinositides play an essential role in numerous cellular functions and, among the enzymes implicated in these processes, phosphoinositide-specific phospholipase C beta1 (PI-PLCbeta1) is one of the key regulators. In the present study, a fluorescence in situ hybridization (FISH) approach was used to investigate PI-PLCbeta1 gene copy number alterations in various types of breast cancer differing in their invasiveness and proliferative activity, according to their mitotic index. At the molecular level, we also performed both real-time PCR and immunohistochemical analyses on PI-PLCbeta1 to further investigate its expression in primary breast cancers. Finally, we analyzed the correlation between PI-PLCbeta1 gene copy number and clinicopathological parameters. Our results show that most of our cases had aneusomies on the PI-PLCbeta1 locus (20p12) and amplification of this specific region was the most frequent alteration observed. Our findings also indicate that the amplification of the region containing the PI-PLCbeta1 gene was mostly related to the mitotic index, rather than to the invasion status. Finally, even though our case series is limited, PI-PLCbeta1 gene amplification seems to be correlated to clinicopathological parameters. PMID- 22076474 TI - Role of p21 as a determinant of 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl] diamantane response in human HCT-116 colon carcinoma cells. AB - 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD) induces growth inhibition in human cancer cells. In our previous study, we discovered that DPD irreversibly inhibits the growth of Colo 205 colon cancer cells at the G0/G1 phase and induces cell differentiation. However, the detailed mechanism is still unknown. In this study, we examined the functional importance of p21 and p53 in DPD-induced anticancer effects. We used three isogenic cell lines, HCT-116, HCT 116 p53-/- and HCT-116 p21-/-, to evaluate the roles of p21 and p53 in the in vitro anticancer effects of DPD. The in vivo anti-proliferative effect of DPD was demonstrated by HCT-116 and HCT-116 p21-/- xenograft models. DPD significantly inhibited the growth as well as increased the number of HCT-116 cells in the G0/G1 phase, but not in HCT-116 p53-/- and HCT-116 p21-/- cells examined by flow cytometry. Additionally, western blot analysis showed that DPD treatment induced p21, but not p53 protein expression in HCT-116 cells. The p21-associated cell cycle regulated proteins, such as cyclin D, CDK4 and pRb were decreased after DPD treatment in HCT-116 cells. The DPD-increased G0/G1 phase and induced cell cycle regulated protein expression were not observed in HCT-116 p21-/- and HCT-116 p53 /- cells. DPD decreased cell migration in HCT-116 and HCT-116 p53-/- but not in HCT-116 p21-/- cells. p21 was required for the DPD-induced in vitro anti-colon cancer effect. The in vivo study also showed that DPD significantly inhibited tumor growth through p21 signaling. Our results clearly demonstrate that DPD induced in vitro and in vivo anticancer effects through the activation of p21 in HCT-116 cells. PMID- 22076475 TI - An electrochemical gas sensor based on paper supported room temperature ionic liquids. AB - A sensitive and fast-responding membrane-free amperometric gas sensor is described, consisting of a small filter paper foil soaked with a room temperature ionic liquid (RTIL), upon which three electrodes are screen printed with carbon ink, using a suitable mask. It takes advantage of the high electrical conductivity and negligible vapour pressure of RTILs as well as their easy immobilization into a porous and inexpensive supporting material such as paper. Moreover, thanks to a careful control of the preparation procedure, a very close contact between the RTIL and electrode material can be achieved so as to allow gaseous analytes to undergo charge transfer just as soon as they reach the three phase sites where the electrode material, paper supported RTIL and gas phase meet. Thus, the adverse effect on recorded currents of slow steps such as analyte diffusion and dissolution in a solvent is avoided. To evaluate the performance of this device, it was used as a wall-jet amperometric detector for flow injection analysis of 1-butanethiol vapours, adopted as the model gaseous analyte, present in headspace samples in equilibrium with aqueous solutions at controlled concentrations. With this purpose, the RTIL soaked paper electrochemical detector (RTIL-PED) was assembled by using 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide as the wicking RTIL and printing the working electrode with carbon ink doped with cobalt(II) phthalocyanine, to profit from its ability to electrocatalyze thiol oxidation. The results obtained were quite satisfactory (detection limit: 0.5 MUM; dynamic range: 2-200 MUM, both referring to solution concentrations; correlation coefficient: 0.998; repeatability: +/-7% RSD; long-term stability: 9%), thus suggesting the possible use of this device for manifold applications. PMID- 22076477 TI - Risk prediction models of breast cancer: a systematic review of model performances. AB - The number of risk prediction models has been increasingly developed, for estimating about breast cancer in individual women. However, those model performances are questionable. We therefore have conducted a study with the aim to systematically review previous risk prediction models. The results from this review help to identify the most reliable model and indicate the strengths and weaknesses of each model for guiding future model development. We searched MEDLINE (PubMed) from 1949 and EMBASE (Ovid) from 1974 until October 2010. Observational studies which constructed models using regression methods were selected. Information about model development and performance were extracted. Twenty-five out of 453 studies were eligible. Of these, 18 developed prediction models and 7 validated existing prediction models. Up to 13 variables were included in the models and sample sizes for each study ranged from 550 to 2,404,636. Internal validation was performed in four models, while five models had external validation. Gail and Rosner and Colditz models were the significant models which were subsequently modified by other scholars. Calibration performance of most models was fair to good (expected/observe ratio: 0.87-1.12), but discriminatory accuracy was poor to fair both in internal validation (concordance statistics: 0.53-0.66) and in external validation (concordance statistics: 0.56-0.63). Most models yielded relatively poor discrimination in both internal and external validation. This poor discriminatory accuracy of existing models might be because of a lack of knowledge about risk factors, heterogeneous subtypes of breast cancer, and different distributions of risk factors across populations. In addition the concordance statistic itself is insensitive to measure the improvement of discrimination. Therefore, the new method such as net reclassification index should be considered to evaluate the improvement of the performance of a new develop model. PMID- 22076476 TI - The CIRAS study: a case control study to define the clinical, immunologic, and radiographic features of aromatase inhibitor-induced musculoskeletal symptoms. AB - Aromatase inhibitors (AIs) are widely prescribed for post-menopausal hormone receptor-positive breast cancer; however, musculoskeletal symptoms limit their tolerability. The purpose of this study was to determine whether joint pain in women receiving AIs is associated with inflammatory arthritis as measured by the disease activity score-28 (DAS-28), and to evaluate association with tenosynovitis on ultrasound. A total of 48 postmenopausal women with stage I-III breast cancer and hand pain were recruited from the Lombardi Comprehensive Cancer Center. Those receiving AIs were cases (n = 25), and those not receiving AIs were controls (n = 23). During a single study visit, subjects underwent blinded rheumatologic evaluation, DAS-28, health assessment questionnaires, autoantibodies, inflammatory markers, hand X-ray, and hand Duplex ultrasound. There were no significant differences between cases and controls in DAS-28, or inflammatory markers. A positive ANA (titer > 1:160) was found in ten patients, four of whom met criteria for autoimmune disease (two with rheumatoid arthritis and two with Sjogren's syndrome, equally distributed among cases and controls). This highlights the importance of considering underlying autoimmune disease in subjects with musculoskeletal complaints. Morning stiffness was more prolonged in women receiving AIs, but this did not reach statistical significance (P = 0.07). Ultrasound evidence of flexor tenosynovitis was common in both groups. Although tenosynovitis was not correlated with AI use (P = 0.26), there was a trend toward an association between tenosynovitis and morning stiffness (P = 0.089). While aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) were more common in subjects receiving AIs, they were not unique to AI users. There was no association between presence of AIMSS features and other chemotherapy or medication exposures. Although the majority of subjects had been using AIs for more than 6 months, this study did not find evidence for inflammatory arthritis in women with hand pain receiving AIs. Further studies are needed to develop a case definition of AIMSS, and to confirm whether these symptoms are attributable to AI use. PMID- 22076479 TI - Correlation of white female breast cancer incidence trends with nitrogen dioxide emission levels and motor vehicle density patterns. AB - The long-term trend of female breast cancer incidence rates in the United States and some European countries demonstrates a similar pattern: an increasing trend in the last century followed by a declining trend in this century. The well-known risk factors cannot explain this trend. We compared the breast cancer incidence trends obtained from SEER data with the trend of nitrogen dioxides (NOx) emission and monitoring data as well as motor vehicle density data. The upward followed by downward trend of NOx is similar to the breast cancer incidence trend but with an offset of 20 years earlier. Motor vehicles are the major source of NOx emissions. The geographic distribution of motor vehicles density in 1970 in the observed US counties is positively correlated with breast cancer incidence rates (R(2) 0.8418, the correlation coefficient = 0.9175) in 1980-1995. Because both the time trend and geographic pattern are associated with breast cancer incidence rates, further studies on the relationship between breast cancer and air pollution are needed. PMID- 22076480 TI - Paclitaxel sensitivity of breast cancer cells requires efficient mitotic arrest and disruption of Bcl-xL/Bak interaction. AB - Taxanes are being used for the treatment of breast cancer. However, cancer cells frequently develop resistance to these drugs with the subsequent recurrence of the tumor. MDA-MB-231 and T-47D breast cancer cell lines were used to assess the effect of paclitaxel treatment on apoptosis and cell cycle, the possible mechanisms of paclitaxel resistance as well as the enhancement of paclitaxel induced apoptosis based on its combination with phenylethyl isothiocyanate (PEITC). T-47D cells undergo apoptosis in response to paclitaxel treatment. The induction of apoptosis was associated with a robust mitotic arrest and the disruption of Bcl-xL/Bak interaction. By contrary, MDA-MB-231 cells were insensitive to paclitaxel-induced apoptosis and this was associated with a high percentage of cells that slip out of paclitaxel-imposed mitotic arrest and also with the maintenance of Bcl-xL/Bak interaction. The sequential treatment of MDA MB-231 cells with PEITC followed by paclitaxel inhibited the slippage induced by paclitaxel and increased the apoptosis induction achieved with any of the drugs alone. In breast cancer tissues, high Bcl-xL expression was correlated with a shorter time of disease-free survival in patients treated with a chemotherapeutic regimen that contains paclitaxel, in a statistically significant way. Thus, resistance to paclitaxel in MDA-MB-231 cells is related to the inability to disrupt the Bcl-xL/Bak interaction and increased slippage. In this context, the combination of a drug that induces a strong mitotic arrest, such as paclitaxel, with another that inhibits slippage, such as PEITC, translates into increased apoptotic induction. PMID- 22076478 TI - A short-term biomarker modulation study of simvastatin in women at increased risk of a new breast cancer. AB - Observational studies have demonstrated a decreased incidence of cancers among users of HMG CoA reductase inhibitors (statins) and a reduced risk of recurrence among statin users diagnosed with early stage breast cancer. We initiated a prospective study to identify potential biomarkers of simvastatin chemopreventive activity that can be validated in future trials. The contralateral breast of women with a previous history of breast cancer was used as a high-risk model. Eligible women who had completed all planned treatment of a prior stage 0-III breast cancer received simvastatin 40 mg orally daily for 24-28 weeks. At baseline and end-of-study, we measured circulating concentrations of high sensitivity C-reactive protein (hsCRP), estrogens, and fasting lipids; breast density on contralateral breast mammogram; and quality of life by Rand Short Form 36-Item health survey. Fifty women were enrolled with a median age of 53 years. Total cholesterol, LDL cholesterol, triglyceride, and hsCRP fell significantly during the study (P values < 0.001, <0.001, 0.003, and 0.05, respectively). Estrone sulfate concentrations decreased with simvastatin treatment (P = 0.01 overall), particularly among post-menopausal participants (P = 0.006). We did not observe a significant change in circulating estradiol or estrone concentrations, contralateral mammographic breast density, or reported physical functioning or pain scores. This study demonstrates the feasibility of short-term biomarker modulation studies using the contralateral breast of high-risk women. Simvastatin appears to modulate estrone sulfate concentrations and its potential chemopreventive activity in breast cancer warrants further investigation. PMID- 22076481 TI - Expression of SPRR3 is associated with tumor cell proliferation in less advanced stages of breast cancer. AB - Small proline rich repeat protein 3 (SPRR3), a member of the SPRR family of cornified envelope precursor proteins, is a marker for terminal squamous cell differentiation. Previously, this laboratory showed that SPRR3 is strongly upregulated in colorectal tumors, and is involved in the tumorigenesis. The current study was performed to investigate the expression status and effect of SPRR3 in breast cancers (BCs). SPRR3 expression was examined by immunohistochemistry in 241 tumor samples from BC patients. SPRR3 was overexpressed in more than half of all BC samples. SPRR3 overexpression was significantly associated with less advanced stage (0-1 vs. II-III) and the absence of lymph node metastasis (P = 0.004 and 0.013, respectively). HER2/neu overexpression was closely correlated with SPRR3 overexpression in a multivariate analysis (OR, 3.23, P = 0.017). To assess the influence of SPRR3 on cell proliferation and related signaling pathways, SPRR3-transfected clones from the SPRR3-negative T-47D human BC cell line were generated. Among the total of six SPRR3-overexpressing clones, five showed marked proliferation compared with SPRR3 nonexpressing control cells from day 3 of culture (P < 0.001). The SPRR3 overexpressing BC clones showed increased phosphorylation of AKT and MDM2, p21 overexpression, and p53 downregulation. Furthermore, phosphorylation of MEK and MAPK was markedly increased. This study demonstrates that SPRR3 promotes BC cell proliferation by enhancing p53 degradation via the AKT and MAPK pathways and is, therefore, a potential novel therapeutic target for less advanced stages of BC. PMID- 22076482 TI - The assessment of colour perception, naming and knowledge: a new test device with a case study. AB - Besides ocular diseases, also cerebral damage may cause colour vision deficits; cerebral lesions may be associated with a variety of clinical conditions that impair colour processing. This study presents procedures and normative data for a rapid, comprehensive seven-test battery aimed at assessing colour perception, colour naming and object colour knowledge. The norms, obtained from 96 healthy Italian participants, allow normality/pathology judgements on the basis of one sided tolerance limits, after adjusting the score of each test for the demographic variables of the proband subjects. We also report, as an example, use of the battery in a stroke patient; this patient was chosen because her lesion affected the left temporal-occipital cortex, an area sometimes associated with a deficit of colour processing. The patient resulted normal on colour perception and colour name retrieval, but defective on object colour knowledge probed using the stimulus name. For the sound definition of the functional locus of cognitive impairment at the single case level, a multi-faceted set of tasks is necessary. PMID- 22076485 TI - Oil-water interfacial self-assembly: a novel strategy for nanofilm and nanodevice fabrication. AB - How to integrate individual nanostructures into macroscopic thin films has become one of the most intriguing fields in nanoscience and nanotechnology due to the unique properties and important applications of these functional films. Since being discovered in 2004, oil-water interfacial self-assembly of nanostructures has become a novel strategy for fabrication of nanofilms. It is a powerful bottom up approach for film fabrication due to the low cost and high efficiency, and is simple and universal for almost all low-dimensional nanostructures. In this article, we provide a critical review of the state-of-the-art research activities in this burgeoning self-assembly strategy. We first discuss the thermodynamic mechanism of the oil-water interfacial self-assembly, then the self-assembly of various low-dimensional nanostructures including nanoparticles, one-dimensional (1D) nanostructures, two-dimensional (2D) nanostructures at an oil-water interface developed so far to fabricate high-quality nanofilms. Finally, we present some progress on the construction of functional nanofilm-based nanodevices from this novel strategy based on our research. We conclude this review with critical comments on advantages and the experimental challenges, and further propose the future research and development of this self-assembly strategy for nanodevice construction (105 references). PMID- 22076483 TI - Immersion autometallographic demonstration of pathological zinc accumulation in human acute neural diseases. AB - Zinc is the second most prevalent trace element in the body and is present in particularly large concentrations in the mammalian brain. In animal experiments, several lines of studies show that zinc is involved in the pathological process of ischemia, epilepsy, and mechanical head trauma. However, little is known about the change of zinc in the human neural diseases. In the present study, using immersion autometallography, we found that pathological zinc accumulation was extensively present in the human neurons following ischemia, epilepsy, and mechanical head trauma. Under H&E, apparently damaged neurons were observed in all of the brain regions that showed zinc ions labeled neuronal somata. In conclusion, the data provide the evidence of an active involvement of zinc in neuronal damage. PMID- 22076484 TI - Induction of oxidative stress and inhibition of superoxide dismutase expression in rat cerebral cortex and cerebellum by PTU-induced hypothyroidism and its reversal by curcumin. AB - The present study was carried out to elucidate the effectiveness of curcumin in ameliorating the expression of superoxide dismutase (SOD) in cerebral cortex and cerebellum of rat brain under 6-propyl-2-thiouracil (PTU)-induced hypothyroidism. Induction of hypothyroidism in adult rats by PTU resulted in augmentation of lipid peroxidation (LPx), an index of oxidative stress in cerebellum but not in cerebral cortex. Curcumin-supplementation to PTU-treated (hypothyroid) rats showed significant reduction in the level of LPx in both the regions of brain. The decreased translated products (SOD1 and SOD2) and the unchanged activity of SOD in cerebral cortex of PTU-treated rats were increased on supplementation of curcumin to the hypothyroid rats. Declined translated products of SOD1 and SOD2 in cerebellum of PTU-treated rats were alleviated on administration of curcumin to hypothyroid rats. On the other hand, the decreased activity of SOD in cerebellum of PTU-treated rats was further declined on administration of curcumin to the hypothyroid rats. Results of the present investigation indicate that curcumin differentially modulates the expression of superoxide dismutase in rat brain cortex and cerebellum under PTU-induced hypothyroidism. PMID- 22076486 TI - The role of magnocellular signals in oculomotor attentional capture. AB - While it is known that salient distractors often capture covert and overt attention, it is unclear whether salience signals that stem from magnocellular visual input have a more dominant role in oculomotor capture than those that result from parvocellular input. Because of the direct anatomical connections between the magnocellular pathway and the superior colliculus, salience signals generated from the magnocellular pathway may produce greater oculomotor capture than those from the parvocellular pathway, which could be potentially harder to overcome with "top-down," goal-directed guidance. Although previous research has addressed this with regard to magnocellular transients, in the current research, we investigated whether a static singleton distractor defined along a dimension visible to the magnocellular pathway would also produce enhanced oculomotor capture. In two experiments, we addressed this possibility by comparing a parvo biased singleton condition, in which the distractor was defined by isoluminant chromatic color contrast, with a magno + parvo singleton condition, in which the distractor also differed in luminance from the surrounding objects. In both experiments, magno + parvo singletons elicited faster eye movements than parvo only singletons, presumably reflecting faster information transmission in the magnocellular pathway, but magno + parvo singletons were not significantly more likely to produce oculomotor capture. Thus, although magnocellular salience signals are available more rapidly, they have no sizable advantage over parvocellular salience signals in controlling oculomotor orienting when all stimuli have a common onset. PMID- 22076487 TI - EventRiver: visually exploring text collections with temporal references. AB - Many text collections with temporal references, such as news corpora and weblogs, are generated to report and discuss real life events. Thus, event-related tasks, such as detecting real life events that drive the generation of the text documents, tracking event evolutions, and investigating reports and commentaries about events of interest, are important when exploring such text collections. To incorporate and leverage human efforts in conducting such tasks, we propose a novel visual analytics approach named EventRiver. EventRiver integrates event based automated text analysis and visualization to reveal the events motivating the text generation and the long term stories they construct. On the visualization, users can interactively conduct tasks such as event browsing, tracking, association, and investigation. A working prototype of EventRiver has been implemented for exploring news corpora. A set of case studies, experiments, and a preliminary user test have been conducted to evaluate its effectiveness and efficiency. PMID- 22076488 TI - Visual reasoning about social networks using centrality sensitivity. AB - In this paper, we study the sensitivity of centrality metrics as a key metric of social networks to support visual reasoning. As centrality represents the prestige or importance of a node in a network, its sensitivity represents the importance of the relationship between this and all other nodes in the network. We have derived an analytical solution that extracts the sensitivity as the derivative of centrality with respect to degree for two centrality metrics based on feedback and random walks. We show that these sensitivities are good indicators of the distribution of centrality in the network, and how changes are expected to be propagated if we introduce changes to the network. These metrics also help us simplify a complex network in a way that retains the main structural properties and that results in trustworthy, readable diagrams. Sensitivity is also a key concept for uncertainty analysis of social networks, and we show how our approach may help analysts gain insight on the robustness of key network metrics. Through a number of examples, we illustrate the need for measuring sensitivity, and the impact it has on the visualization of and interaction with social and other scale-free networks. PMID- 22076489 TI - Boceprevir. AB - Boceprevir is a hepatitis C virus (HCV) serine protease NS3 inhibitor that has recently been approved by the U.S. Food and Drug Administration, the European Medicines Agency and Health Canada for the treatment of chronic genotype 1 HCV infection. It has potent in vitro antiviral activity against HCV genotypes 1a and 1b and is primarily metabolized via the aldoketoreductase pathway with minor cytochrome P450 3A4 metabolism. Boceprevir is well tolerated with few drug-drug interactions which are easy to manage; no dose adjustment is required in patients with hepatic or renal impairment. Phase I trials of boceprevir demonstrated favorable pharmacokinetic, metabolic and safety profiles. Phase II and III trials of boceprevir confirmed the antiviral activity of the drug and its use at a dose of 800 mg three times daily. Clinical trials in treatment-naive and previously treated HCV-infected patients demonstrated a 26% and 45% (respectively) improvement in sustained viral response when boceprevir was added to standard pegylated interferon and ribavirin anti-HCV therapy. Boceprevir is the first-in class of an exciting new phase of HCV treatment. PMID- 22076490 TI - Edoxaban for the prevention of thromboembolic events after surgery. AB - Without thromboprophylaxis, hospital-acquired deep vein thrombosis following major orthopedic surgery occurs with an incidence of approximately 40-60%, which is why thromboprophylaxis has been standard of care in these cases for more than 20 years. Edoxaban (DU-176b; Lixiana) is a novel, once-daily, orally active antithrombotic agent that directly inhibits factor Xa activity in a potent and selective way. It was recently approved in Japan for the prevention of venous thromboembolism after total knee replacement, total hip replacement and hip fracture surgery. In phase III trials performed in patients eligible for total knee replacement or total hip replacement, edoxaban 30 mg demonstrated a statistically significant reduction in venous thromboembolic events compared with enoxaparin, with no difference between both treatments in the incidence of major bleeding events. Edoxaban is safe and well tolerated, with predictable pharmacokinetics (low intersubject variability and low protein binding), suggesting that coagulation monitoring may not be required. PMID- 22076491 TI - Tramadol hydrochloride/acetaminophen combination for the relief of acute pain. AB - Tramadol hydrochloride/acetaminophen is a combination drug containing tramadol hydrochloride 37.5 mg and acetaminophen 325 mg. The use of 25% less tramadol in the combination product reduces the incidence of tramadol-related adverse events, while the addition of acetaminophen reduces the onset time of analgesia and improves the degree of analgesia. However, there was no clinically significant difference in the pharmacokinetic parameters of tramadol or acetaminophen when the fixed-dose combination was compared with the individual agents after multiple dose administration. The onset time of tramadol hydrochloride/acetaminophen was the fastest at only 17 minutes compared 51 minutes for tramadol and 18 minutes for acetaminophen. This combination has been found to be effective in the management of postoperative pain. It improves pain relief and provides a faster onset and longer duration of action with fewer adverse events than either component separately. It also reduces the severity of pain, photophobia and phonophobia associated with migraine headache. Tramadol hydrochloride/acetaminophen has been shown to be most effective in patients with mild to moderate pain and has a lower risk of serious adverse events. PMID- 22076492 TI - Current treatment options for neuroendocrine tumors. AB - Neuroendocrine tumors are heterogeneous in their clinical behavior and require therapies specially tailored according to staging and grading, origin and expression of peptide receptors. Somatostatin analogues act as antisecretory and antiproliferative agents. Chemotherapy is mandatory for poorly differentiated neuroendocrine carcinomas and is also effective in neuroendocrine tumors of the pancreas and of the bronchial system. For localized neuroendocrine tumors, surgery should be performed with curative intent and is also an option in advanced or metastasized neuroendocrine tumors with the goal to debulk tumor masses. Local ablative therapies may be applied to decrease tumor load in the liver; however, results are often of short duration. Peptide receptor radiotherapy is a new treatment method applying radionuclide-targeted somatostatin receptor agonists for internal cytotoxic radiotherapy in somatostatin receptor-expressing neuroendocrine tumors. Retrospective and prospective clinical studies indicate prolonged progression-free survival and overall survival of patients responding by stable disease or any kind of remission with this innovative treatment, which is, however, available only in a few specialized centers. Finally, small-molecule inhibitors of vascular endothelial growth factor and serine/threonine-protein kinase mTOR pathways have been shown to delay progression in patients with neuroendocrine tumors. In summary, treatment options for neuroendocrine tumors have expanded considerably in the last years leading to prolonged overall survival. PMID- 22076493 TI - A report from the European Society of Cardiology Congress 2011 (August 27-31, 2011 -- Paris, France). AB - Paris, known as the city of light or the illuminated city, is, thus, an appropriate site for a major international conference in which advances in research and new findings and observations are reported and discussed, as was the case during this year's European Society of Cardiology meeting. Indeed, not only were new results from major clinical trials presented, but initial clinical and preclinical research results were also reported during the meeting oral and poster sessions which, in many cases, represent major steps towards improved cardiovascular pharmacotherapy for many common diseases shortening the lives of people around the world. For those who could not attend the meeting, Drugs of Today has wrapped up the major take-home messages from the meeting in the following report. PMID- 22076494 TI - Mechanistic links between oxidative/nitrosative stress and tumor necrosis factor alpha in letrozole-induced murine polycystic ovary: biochemical and pathological evidences for beneficial effect of pioglitazone. AB - This study aimed to investigate the possible relationship between ovarian functionality and the oxidative response during cystogenesis induced by hyperandrogenization with letrozole and examine protective effect of the peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, pioglitazone (PIO), in polycystic ovary (PCO). Ovarian cysts were induced by oral administration of letrozol (1 mg/kg/day) for 21 consecutive days in the female rats. Effective dose of PIO (20 mg/kg/day) was administrated orally for 21 days. Serum estradiol (E), progesterone (P), testosterone (T), and the ovarian immunomodulator prostaglandin E (PGE) were analyzed as biomarkers of ovarian function. To determine the role of oxidative stress in PCO, the level of cellular lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and peroxynitrite (ONOO), and tumor necrosis factor alpha (TNF alpha) as a marker of inflammation and apoptosis were measured in serum and the ovaries. Letrozole-induced PCO in rats exhibited a significant increase in LPO and ONOO in serum and ovary while significantly decreased serum and ovarian SOD, CAT, and GPx. Serum T and TNF-alpha, and ovarian PGE were increased in animals with cysts compared with healthy controls, while E and P diminished. When compared to control group, letrozole-treated group showed irregular sexual cycles, polycystic ovaries characterized by high incidence of sub-capsular ovarian cyst with diminished or scant granulosa cell layer, increased number of atretic pre-antral and antral follicles and absence of corpus luteum. There were almost no primary, secondary, and tertiary follicles observed in PCO rats. All measured parameters were improved by PIO and reached close to normal levels. The present study further supports the role of oxidative/nitrosative stress and infiammatory responses in the pathogenesis of letrozole-induced hyperandrogenic PCO rats. Results indicate that PIO is able to exert direct antioxidative and anti-inflammatory effects on the endocrine, biochemical, and pathological alterations independent of its possible effects mediated via increased insulin sensitivity in hyperandrogenized PCO. PMID- 22076495 TI - Peripheral blood dendritic cells in alcoholic and autoimmune liver disorders. AB - Little is known about effects of alcohol consumption on dendritic cell (DC) function and resultant immune response. However, quantitative and qualitative disturbances of DCs are speculated to be involved in alcohol-related as well as in other liver pathology. The present study aimed to evaluate changes in circulating DC subsets in alcoholic liver disease (N = 43), autoimmune hepatitis (N = 26) and primary biliary cirrhosis (N = 20). DCs isolated from the peripheral blood of recruited participants were stained with monoclonal antibodies against blood dendritic cell antigens (BDCAs) and estimated using the flow cytometry. Myeloid DCs were defined as BDCA-1(+)/CD19(-) cells, and lymphoid DCs as BDCA 2(+)/CD123(+) cells. Total numbers of circulating DCs in subjects with some liver diseases were markedly lower than in the healthy participants (p = 0.03). There was a significantly lower percentage of circulating BDCA-2(+)/CD123(+) (p = 0.02), and a tendency for the percentage of circulating BDCA-1(+)/CD19(-) cells to decrease in patients with liver diseases compared to the controls (p = 0.09). These results may suggest that decreased numbers of DCs may be responsible for reduced adaptive immune responses and increased susceptibility to infections and cancer development observed in patients exposed to alcohol. Moreover, numerical abnormalities of DCs may contribute to the breakdown of self-tolerance, a feature of autoimmune diseases. PMID- 22076497 TI - Sesamol attenuates oxidative stress-mediated experimental acute pancreatitis in rats. AB - Acute pancreatitis is a potentially fatal disease with no known cure. The initial events in acute pancreatitis may occur within the acinar cells. We examined the effect of sesamol on (i) a cerulein-induced pancreatic acinar cancer cell line, AR42J, and (ii) cerulein-induced experimental acute pancreatitis in rats. Sesamol inhibited amylase activity and increased cell survival. It also inhibited medium lipid peroxidation and 8-hydroxydeoxyguanosine in AR42J cells compared with the cerulein-alone groups. In addition, in cerulein-treated rats, sesamol inhibited serum amylase and lipase levels, pancreatic edema, and lipid peroxidation, but it increased pancreatic glutathione and nitric oxide levels. Thus, we hypothesize that sesamol attenuates cerulein-induced experimental acute pancreatitis by inhibiting the pancreatic acinar cell death associated with oxidative stress in rats. PMID- 22076496 TI - Long-term exposure to nonylphenol affects insulin signaling in the liver of adult male rats. AB - In the present study, we sought to investigate the long-term effects of nonylphenol (NP) on insulin signaling and glucose metabolism in liver. Furthermore, reactive oxygen species (ROS) in liver was evaluated as it is known to induce insulin resistance. Rats were administered NP by oral gavage at the doses of 15, 150 and 1500 MUg/ kg body weight per day for 45 days. Hydrogen peroxide (H(2)O(2)) generation and lipid peroxidation were increased, and the activities of antioxidant enzymes were decreased in the liver of NP-treated rats. NP increased the plasma glucose and insulin levels and altered the enzymes of carbohydrate metabolism. Decrease in the protein levels of insulin signaling molecules insulin receptor (IR), IR substrate (IRS)-1, IRS-2 and phosphatidylinositol-3-kinase were observed with parallel increase in H(2)O(2) levels in the liver of NP-treated rats. These results suggest that NP downregulates insulin signaling in liver, which could be due to ROS production and oxidative damage. PMID- 22076498 TI - Reassortment Networks and the evolution of pandemic H1N1 swine-origin influenza. AB - Prior research developed Reassortment Networks to reconstruct the evolution of segmented viruses under both reassortment and mutation. We report their application to the swine-origin pandemic H1N1 virus (S-OIV). A database of all influenza A viruses, for which complete genome sequences were available in Genbank by October 2009, was created and dynamic programming was used to compute distances between all corresponding segments. A reassortment network was created to obtain the minimum cost evolutionary paths from all viruses to the exemplar S OIV A/California/04/2009. This analysis took 35 hours on the Cray Extreme Multithreading (XMT) supercomputer, which has special hardware to permit efficient parallelization. Six specific H1N1/H1N2 bottleneck viruses were identified that almost always lie on minimum cost paths to S-OIV. We conjecture that these viruses are crucial to S-OIV evolution and worthy of careful study from a molecular biology viewpoint. In phylogenetics, ancestors are typically medians that have no functional constraints. In our method, ancestors are not inferred, but rather chosen from previously observed viruses along a path of mutation and reassortment leading to the target virus. This specificity and functional constraint render our results actionable for further experiments in vitro and in vivo. PMID- 22076499 TI - Repulsive guidance molecules, novel bone morphogenetic protein co-receptors, are key regulators of the growth and aggressiveness of prostate cancer cells. AB - Repulsive guidance molecule (RGM) family members RGMA, RGMB and RGMC are GPI linked membrane proteins recently identified as co-receptor of bone morphogenetic proteins (BMPs). BMPs are a group of proteins enriched in bone and play important roles in prostate cancer. The current study aimed to investigate roles played by RGMs in prostate cancer. Expression of RGMs was examined in prostate cancer cell lines and prostate cancer tissues using RT-PCR and immunohistochemical staining. Knockdown of each RGM in prostate cancer cells was performed using the respective anti-RGMA, RGMB and RGMC transgenes. A variety of in vitro function tests were employed to analyze the influence on cancer cell functions by RGM knockdown. The implications of RGM knockdown in BMP signalling were also examined using both Western blot and real-time quantitative PCR. Knockdown of RGMA had no effect on cell growth, migration and invasion, but promoted cell-matrix adhesion. Knockdown of RGMB and RGMC increased growth and adhesion, but only RGMB knockdown increased capacities of migration and invasion in PC-3 cells. Further investigations showed an increase in Smad-3 activation and reduced levels of Smad-1 in PC-3 cells by RGMB and RGMC knockdown, and also an up-regulation of ID1, a BMP target gene particularly in exposure to BMP7. RGMs play inhibitory roles in prostate cancer by suppressing cell growth, adhesion, migration and invasion. RGMs can coordinate Smad-dependent signalling of BMPs in prostate cancer cells. PMID- 22076500 TI - Intermittent hypobaric hypoxia preconditioning induced brain ischemic tolerance by up-regulating glial glutamate transporter-1 in rats. AB - Several studies showed that the up-regulation of glial glutamate transporter-1 (GLT-1) participates in the acquisition of brain ischemic tolerance induced by cerebral ischemic preconditioning or ceftriaxone pretreatment in rats. To explore whether GLT-1 plays a role in the acquisition of brain ischemic tolerance induced by intermittent hypobaric hypoxia (IH) preconditioning (mimicking 5,000 m high altitude, 6 h per day, once daily for 28 days), immunohistochemistry and western blot were used to observe the changes in the expression of GLT-1 protein in hippocampal CA1 subfield during the induction of brain ischemic tolerance by IH preconditioning, and the effect of dihydrokainate (DHK), an inhibitor of GLT-1, on the acquisition of brain ischemic tolerance in rats. The basal expression of GLT-1 protein in hippocampal CA1 subfield was significantly up-regulated by IH preconditioning, and at the same time astrocytes were activated by IH preconditioning, which appeared normal soma and aplenty slender processes. The GLT-1 expression was decreased at 7 days after 8-min global brain ischemia. When the rats were pretreated with the IH preconditioning before the global brain ischemia, the down-regulation of GLT-1 protein was prevented clearly. Neuropathological evaluation by thionin staining showed that 200 nmol DHK blocked the protective role of IH preconditioning against delayed neuronal death induced normally by 8-min global brain ischemia. Taken together, the up-regulation of GLT 1 protein participates in the acquisition of brain ischemic tolerance induced by IH preconditioning in rats. PMID- 22076501 TI - Epicatechin inhibits human plasma lipid peroxidation caused by haloperidol in vitro. AB - Epicatechin belongs to flavonoids protecting cells against oxidative/nitrative stress. Oxidative/nitrative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics. The aim of our study was to establish the effects of epicatechin and antipsychotics action (the first generation antipsychotic (FGA)--haloperidol and the second generation antipsychotic (SGA)--amisulpride) on peroxidation of plasma lipids in vitro. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The properties of epicatechin were also compared with the action of a well characterized antioxidative commercial polyphenol resveratrol (3,4',5-trihydroxystilbene) and quercetin (3,5,7,3',4' pentahydroxyflavone). Amisulpride, contrary to haloperidol (after 1 and 24 h) does not significantly influence the increase of plasma TBARS level in comparison with control samples (P > 0.05). After incubation (1 and 24 h) of plasma with haloperidol in the presence of epicatechin we observed a significantly decreases the level of TBARS (P < 0.001, P < 0.001, respectively). In our other experiments, we found that epicatechin also decreased the amount of TBARS in human plasma treated with amisulpride. In conclusion, the presented results indicate that epicatechin-the major polyphenolic component of green tea reduced significantly human plasma lipid peroxidation caused by haloperidol. Moreover, epicatechin was found to be a more effective antioxidant, than the solution of pure resveratrol or quercetin. PMID- 22076502 TI - FoxO3a changes in pyramidal neurons and expresses in non-pyramidal neurons and astrocytes in the gerbil hippocampal CA1 region after transient cerebral ischemia. AB - The forkhead box O (FoxO) proteins regulate processes ranging from cell longevity to cell apoptosis and function as transcription factors. FoxO3a is expressed throughout the brain including the hippocampus. In the present study, we investigated the changes in FoxO3a immunoreactivity and its protein levels in the gerbil hippocampal CA1 region after 5 min of transient global cerebral ischemia. FoxO3a immunoreactivity and protein levels in the ischemic CA1 region, which is very vulnerable to ischemic damage, were slightly decreased from 3 h after ischemia-reperfusion (I-R) and maintained until 12 h after I-R. One and 2 days after I-R, FoxO3a immunoreactivity and protein levels were similar to those in the sham-operated group. At 3 days after I-R, FoxO3a immunoreactivity and protein levels were markedly increased in the CA1 region. FoxO3a immunoreactivity was hardly detected in pyramidal neurons from 5 days after I-R; however, at 5 days after I-R, FoxO3a immunoreactivity was detected in astrocytes and GABAergic interneurons of the ischemic CA1 region. These results indicate that both FoxO3a immunoreactivity and protein levels are distinctively altered in the ischemic CA1 region after transient cerebral ischemia, and that the changes in FoxO3a expression may be related to the ischemia-induced delayed neuronal death. PMID- 22076503 TI - Blunting half of the double-edged sword: potential use of interleukin-10 to protect bone marrow-derived cells after myocardial infarction. PMID- 22076504 TI - Opening the field of integrin biology to "biased agonism". PMID- 22076505 TI - Widespread promiscuous genetic information transfer from DNA to RNA. PMID- 22076506 TI - Meeting report for Basic Cardiovascular Sciences 2011 Scientific Sessions: from concept to clinic: leading cardiovascular translational science. PMID- 22076507 TI - Grown up mice from gene-corrected iPS cells. PMID- 22076508 TI - Methylation profiles of the BRCA1 promoter in hereditary and sporadic breast cancer among Han Chinese. AB - The development of breast cancer is a multistep process associated with complex changes in host gene expression patterns including inactivation of tumor suppressor genes and activation of oncogenes. Critically, hereditary predisposition plays a significant role in cancer susceptibility. However, mutation of the BRCA1 gene is found only in the minority of hereditary breast cancer, which indicates that there might be alternative, novel mechanisms contributing to inactivation of the BRCA1 gene. Studies have shown that aberrant methylation of genomic DNA plays an important role in carcinogenesis. The aim of this study was to investigate whether DNA methylation may be an alternative mechanism for the inactivation of BRCA1 as an epigenetic modification of the genome and whether hereditary breast cancer has a different BRCA1 methylation phenotype pattern than sporadic breast cancer. The pattern of CpG island methylation within the promoter region of BRCA1 was assessed by bisulfite sequencing DNA from peripheral blood cells of 72 patients with hereditary predisposition but without BRCA1 mutations and 30 sporadic breast cancer controls. The overall methylation level in patients with hereditary predisposition was significantly lower than that in the sporadic control group. However, patients with hereditary predisposition showed a significantly higher methylation susceptibility for the sites -518 when compared to controls. These results suggest that there might be different BRCA1 promoter methylation levels and patterns in sporadic and hereditary breast cancer in peripheral blood DNA. These findings may facilitate the early diagnosis of hereditary breast cancer. PMID- 22076510 TI - EU bans embryonic stem cell patents but decision may have limited implications. PMID- 22076511 TI - Managing febrile seizures in children. AB - A febrile seizure is a benign convulsion that occurs in infants or small children and is brought on by fever without evidence of meningitis or encephalitis. Little is known about the etiology, but pharmacologic treatment should be easy to administer, have virtually no adverse effects, and be efficacious. Supporting the family is also crucial during this stressful event. PMID- 22076514 TI - Carvedilol: a countermeasure to heart failure. AB - Initially used primarily as an antihypertensive, the beta-blocker carvedilol is now being used to alleviate heart failure, significantly reducing hospitalizations and mortality. In this article, we discuss the pathophysiology of heart failure; carvedilol's action, long-term benefits, and administration; and potential short-term adverse effects. PMID- 22076509 TI - Induced pluripotent stem cells--opportunities for disease modelling and drug discovery. AB - The ability to generate induced pluripotent stem cells (iPSCs) from patients, and an increasingly refined capacity to differentiate these iPSCs into disease relevant cell types, promises a new paradigm in drug development - one that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSCs that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSCs can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling a 'disease in a dish' and for testing compounds against human disease phenotypes in vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets and enhance the probability of clinical success of new drugs. PMID- 22076515 TI - What nursing has learned from famous traumas. AB - The deaths of three celebrities shed light on where trauma care needs to improve and remind us how far we have already come. PMID- 22076516 TI - The effects of an advanced practice nurse-directed heart failure program. AB - This study sought to determine if an inpatient heart failure program directed by an advanced practice nurse could affect length of hospital stay, mortality, readmission rates, and adherence to the recommended clinical regimen. PMID- 22076517 TI - Fomepizole. PMID- 22076518 TI - Evaluating a nurse practitioner service. AB - Increasingly, nurse practitioners are filling resident and house staff shortages by moving into acute care settings. This article compares a nurse practitioner/attending collaborative service with a traditional physician-based service in terms of patient outcomes and patient, physician, and staff satisfaction. PMID- 22076519 TI - On hold in the ED. PMID- 22076520 TI - Professional boundaries: Staying in the lines. AB - Nurses must set professional boundaries for their relationships with patients. Managers can teach nurses the meaning of boundary crossings, boundary violations, and staying in the lines. PMID- 22076522 TI - The bloodborne pathogens standard, 2001: what's changed? AB - Learn how to facilitate implementation of OSHA's strengthened sharps safety requirements. PMID- 22076523 TI - A transitional feeding protocol for critically ill patients. AB - Critically ill patients often are malnourished and in protein catabolism, impairing their ability to heal. A transitional feeding protocol, aimed at keeping patients adequately nourished while they move from parenteral or enteral nutrition to an oral diet, can improve outcomes for surgical and medical intensive care unit patients. PMID- 22076524 TI - A ladder or a tree? PMID- 22076525 TI - The risk of a second hip fracture in patients after their first hip fracture. AB - We investigated the incidence of additional fractures and the rate of prescription of osteoporotic pharmacotherapy after an initial hip fracture. We surveyed female patients aged 65 and over who sustained their first hip fracture between January 1, 2006, and December 31, 2007, treated at 25 hospitals in five geographic areas in Japan. Data for 1 year after the first hip fracture were collected from medical records, and questionnaires were mailed to all patients. In total, 2,663 patients were enrolled, and 335 patients were excluded based on exclusion criteria. The analysis was performed on 2,328 patients. During the 1 year follow-up period 160 fractures occurred in 153 patients and 77 subsequent hip fractures occurred in 77 patients. The incidence of all additional fractures among patients who sustained their first hip fracture was 70 (per 1,000 person year) and that for second hip fracture was 34. In comparison to the general population, women >=65 years of age who sustained an initial hip fracture were four times as likely to sustain an additional hip fracture. Antiosteoporosis pharmacotherapy was prescribed for 436 patients (18.7%), while 1,240 patients (53.3%) did not receive any treatment during the 1-year period. Patients who have sustained one hip fracture have a higher risk of a second hip fracture compared to the general population, and most of these women receive no pharmaceutical treatment for osteoporosis. PMID- 22076526 TI - Association study of polymorphisms in the SOST gene region and parameters of bone strength and body composition in both young and elderly men: data from the Odense Androgen Study. AB - By means of different genetic association studies the SOST gene, encoding sclerostin, has repeatedly been suggested to regulate bone mineral density (BMD) and osteoporosis susceptibility. This study aimed at a further understanding of the importance of two previously studied single-nucleotide polymorphisms in the SOST gene, rs10534024 (SRP3) and rs9902563 (SRP9), in the Odense Androgen Study (OAS) cohort. This cohort includes a total of 1,383 Danish men from two different age groups, 20-29 years (n = 783) and 60-74 years (n = 600), and is well characterized. Subjects were phenotyped for BMD at several sites and additionally for body composition and hip geometric parameters. In a combined analysis of the young and the elderly OAS, no associations were found for SRP3 either with BMD or with hip geometry. Instead, we found that this polymorphism had a relatively large effect on weight (-1.149 kg) and body mass index (-0.389 kg/m(2)) (P = 0.021 and 0.006 under a codominant model). For SRP9, a significant association was found for femoral neck BMD (+0.020 g/cm(2), P = 0.020) and a trend toward significance for hip geometry (buckling ratio of the narrow neck) but only when considering a recessive effect of the minor allele (C). No age-specific effects were found for either of the two SNPs. In summary, we are the first to find interesting associations between SRP3 and body composition. For SRP9, we replicated a site-specific association with femoral neck BMD. In addition, we report a novel association for this polymorphism with hip geometry. PMID- 22076527 TI - Optimization of macroporous 3-D silk fibroin scaffolds by salt-leaching procedure in organic solvent-free conditions. AB - A novel all-aqueous process is described to form three-dimensional porous silk fibroin (SF) scaffolds, which not only avoided the use of organic solvents or harsh chemicals, but also can form scaffolds with various sizes and in large quantities. The scaffolds show a rough surface on the pores and the pores are highly interconnected. The porosity of the scaffolds, which varied between a large range (67.6~99.3%), can be controlled by the SF concentrations and the salt/fibroin ratio. The results of measurements indicated that this novel process can improve and enforce the transformation in SF structure from a random coil to a beta-sheet. Swelling studies showed that the scaffold has excellent properties of hydrophilicity. The cell culture experiments demonstrated that the scaffolds facilitated the human osteosarcoma cells attachment and proliferation in vitro. PMID- 22076528 TI - Mullins effect behaviour under compression in micelle-templated silica and micelle-templated silica/agarose systems. AB - The mechanical properties of bioceramic conformed pieces based on micelle templated silica (MTS) such as SBA15, MCM41 and MCM48 as well as MTS/agarose systems have been evaluated under static and cyclic compressive tests. The MTS pieces exhibited a brittle behaviour. Agarose, a biocompatible and biodegradable hydrogel, has been used to shape ceramic-agarose pieces following a low temperature shaping method. Agarose conferred toughness, ductility and a rubbery consistency up to a 60% strain in ceramic MTS/agarose systems leading to a maximum strength of 10-50 MPa, without losing their initial cylindrical structure. This combination of ceramic and organic matrix contributes to avoiding the inherent brittleness of the bioceramic and enhances the compression resistance of hydrogel. The presence of mechanical hysteresis, permanent deformation after the first cycle and recovery of the master monotonous curve of MTS/agarose systems indicate a Mullins-like effect similar to that found in carbon-filled rubber systems. We report this type of mechanical behaviour, the Mullins effect, for the first time in MTS bioceramics and MTS bioceramic/agarose systems. PMID- 22076529 TI - PAN hollow fiber membranes elicit functional hippocampal neuronal network. AB - This study focuses on the development of an advanced in vitro biohybrid culture model system based on the use of hollow fibre membranes (HFMs) and hippocampal neurons in order to promote the formation of a high density neuronal network. Polyacrylonitrile (PAN) and modified polyetheretherketone (PEEK-WC) membranes were prepared in hollow fibre configuration. The morphological and metabolic behaviour of hippocampal neurons cultured on PAN HF membranes were compared with those cultured on PEEK-WC HF. The differences of cell behaviour between HFMs were evidenced by the morphometric analysis in terms of axon length and also by the investigation of metabolic activity in terms of neurotrophin secretion. These findings suggested that PAN HFMs induced the in vitro reconstruction of very highly functional and complex neuronal networks. Thus, these biomaterials could potentially be used for the in vitro realization of a functional hippocampal tissue analogue for the study of neurobiological functions and/or neurodegenerative diseases. PMID- 22076530 TI - Symptomatic low-grade carotid stenosis with intraplaque hemorrhage and expansive arterial remodeling is associated with a high relapse rate refractory to medical treatment. AB - BACKGROUND: Carotid plaque characteristics influence future risk of stroke considerably. However, the severity of stenosis does not accurately reflect plaque burden in patients with expansive arterial remodeling. OBJECTIVE: To determine the therapeutic outcome of symptomatic carotid low-grade stenosis with vulnerable plaque based on magnetic resonance imaging (MRI) characterization. METHODS: We studied 25 (male, n = 23; age, 74.2 +/- 5.6 years) of 29 consecutive patients with symptomatic carotid low-grade stenosis (<50%) and both high-signal plaque and expansive remodeling on T1-weighted MRIs. The remaining 4 were excluded because of impending stroke. A single antithrombotic and statin were administered, and recurrent ischemic stroke was treated with dual antithrombotics. We considered carotid endarterectomy when recurrence was refractory to aggressive medical treatment. RESULTS: During a 31.3 +/- 16.4-month follow-up, 11 of the 25 patients developed a total of 30 recurrent ischemic events (46.0% per patient-year). The patients' characteristics did not differ significantly between the groups with and without recurrence (n = 11 and n = 14, respectively). Seven of 11 patients in the recurrence group treated with carotid endarterectomy remained free of ischemic events during a postoperative follow-up of 19.1 +/- 14.6 months. CONCLUSION: Symptomatic low-grade carotid stenosis with vulnerable plaque confirmed by MRI was associated with a high rate of stroke recurrence that was refractory to aggressive medical treatment. However, carotid endarterectomy was safe and effective for such patients. Plaque characterization by MRI has the potential for more accurate stroke risk stratification in the management of carotid low-grade stenosis. PMID- 22076531 TI - Are initial radiographic and clinical scales associated with subsequent intracranial pressure and brain oxygen levels after severe traumatic brain injury? AB - BACKGROUND: Prediction of clinical course and outcome after severe traumatic brain injury (TBI) is important. OBJECTIVE: To examine whether clinical scales (Glasgow Coma Scale [GCS], Injury Severity Score [ISS], and Acute Physiology and Chronic Health Evaluation II [APACHE II]) or radiographic scales based on admission computed tomography (Marshall and Rotterdam) were associated with intensive care unit (ICU) physiology (intracranial pressure [ICP], brain tissue oxygen tension [PbtO2]), and clinical outcome after severe TBI. METHODS: One hundred one patients (median age, 41.0 years; interquartile range [26-55]) with severe TBI who had ICP and PbtO2 monitoring were identified. The relationship between admission GCS, ISS, APACHE II, Marshall and Rotterdam scores and ICP, PbtO2, and outcome was examined by using mixed-effects models and logistic regression. RESULTS: Median (25%-75% interquartile range) admission GCS and APACHE II without GCS scores were 3.0 (3-7) and 11.0 (8-13), respectively. Marshall and Rotterdam scores were 3.0 (3-5) and 4.0 (4-5). Mean ICP and PbtO2 during the patients' ICU course were 15.5 +/- 10.7 mm Hg and 29.9 +/- 10.8 mm Hg, respectively. Three-month mortality was 37.6%. Admission GCS was not associated with mortality. APACHE II (P = .003), APACHE-non-GCS (P = .004), Marshall (P < .001), and Rotterdam scores (P < .001) were associated with mortality. No relationship between GCS, ISS, Marshall, or Rotterdam scores and subsequent ICP or PbtO2 was observed. The APACHE II score was inversely associated with median PbtO2 (P = .03) and minimum PbtO2 (P = .008) and had a stronger correlation with amount of time of reduced PbtO2. CONCLUSION: Following severe TBI, factors associated with outcome may not always predict a patient's ICU course and, in particular, intracranial physiology. PMID- 22076532 TI - Diurnal and nocturnal intraocular pressure fluctuations after trabeculectomy. AB - PURPOSE: The aim of this study was to compare diurnal and nocturnal intraocular pressure (IOP) fluctuations before and after trabeculectomy, and to evaluate the potential of trabeculectomy to even out IOP peaks. MATERIALS AND METHODS: Retrospectively, 35 diurnal and nocturnal IOP curves of patients (35 eyes) who underwent trabeculectomy were analyzed. Diurnal and nocturnal IOP profiles were recorded from 06:00 to 23:59 and 00:00 to 06:00, respectively. Follow-up was at least 300 days. Two criteria for success were defined: (1) IOP <=21 mm Hg and at least a 20% IOP reduction from baseline; (2) <18 mm Hg without medication. RESULTS: The preoperative maximum diurnal and nocturnal IOP (IOP(max)) were 26.5 +/- 5.9 and 23.4 +/- 5.2 mm Hg, respectively. The postoperative diurnal and nocturnal IOP(max) were 16 +/- 4.4 and 16 +/- 5.4 mm Hg, respectively. Pre- to postoperative IOP reductions were statistically different (day 40% and night 32%; p < 0.001). Diurnal fluctuation was reduced significantly from 12.1 +/- 4.2 mm Hg preoperatively to 5.6 +/- 2.2 mm Hg postoperatively (reduction of 54%), and nocturnal fluctuation from 7.1 +/- 4.5 to 3.9 +/- 4.1 mm Hg (reduction of 46%, statistically insignificant due to large SD), respectively. Success criteria 1 and 2 were achieved in 71 and 54% of patients at daytime and in 63 and 57% at nighttime (no statistically significant difference detectable). Follow-up was 2.1 +/- 1.7 years. CONCLUSIONS: Trabeculectomy achieves a leveling of IOP(max) in the diurnal-nocturnal comparison. The preoperative fluctuations could be nearly bisected. Relating to the success criteria, the statistical analysis did not reveal a difference in the diurnal-nocturnal comparison. PMID- 22076533 TI - Stress-induced rise in body temperature is repeatable in free-ranging Eastern chipmunks (Tamias striatus). AB - In response to handling or other acute stressors, most mammals, including humans, experience a temporary rise in body temperature (T(b)). Although this stress induced rise in T(b) has been extensively studied on model organisms under controlled environments, individual variation in this interesting phenomenon has not been examined in the field. We investigated the stress-induced rise in T(b) in free-ranging eastern chipmunks (Tamias striatus) to determine first if it is repeatable. We predicted that the stress-induced rise in T(b) should be positively correlated to factors affecting heat production and heat dissipation, including ambient temperature (T(a)), body mass (M(b)), and field metabolic rate (FMR). Over two summers, we recorded both T(b) within the first minute of handling time (T(b1)) and after 5 min of handling time (T(b5)) 294 times on 140 individuals. The mean ?T(b) (T(b5) - T(b1)) during this short interval was 0.30 +/- 0.02 degrees C, confirming that the stress-induced rise in T(b) occurs in chipmunks. Consistent differences among individuals accounted for 40% of the total variation in ?T(b) (i.e. the stress-induced rise in T(b) is significantly repeatable). We also found that the stress-induced rise in T(b) was positively correlated to T(a), M(b), and mass-adjusted FMR. These results confirm that individuals consistently differ in their expression of the stress-induced rise in T(b) and that the extent of its expression is affected by factors related to heat production and dissipation. We highlight some research constraints and opportunities related to the integration of this laboratory paradigm into physiological and evolutionary ecology. PMID- 22076534 TI - An enzymatic bridge between carbohydrate and amino acid metabolism: regulation of glutamate dehydrogenase by reversible phosphorylation in a severe hypoxia tolerant crayfish. AB - Glutamate dehydrogenase (GDH) (EC 1.4.1.3) is a crucial enzyme involved in bridging two metabolic pathways, gating the use of glutamate for either amino acid metabolism, or carbohydrate metabolism. The present study investigated GDH from tail muscle of the freshwater crayfish Orconectes virilis exploring changes to kinetic properties, phosphorylation levels and structural stability between two forms of the enzyme (aerobic control and 20-h severe hypoxic). Evidence indicated that GDH was converted to a high phosphate form under oxygen limitation. ProQ Diamond phosphoprotein staining showed a 42% higher bound phosphate content on GDH from muscle of severely hypoxic crayfish compared with the aerobic form, and treatment of this GDH with commercial phosphatase (alkaline phosphatase), and treatments that stimulated the activities of different endogenous protein phosphatases (stimulating PP1 + PP2A, PP2B, and PP2C) yielded significant increases in the fold activation by ADP of GDH from both control and severe hypoxic conditions. By contrast, stimulation of the activities of endogenous protein kinases (AMPK, PKA or CaMK) significantly reduced the ADP fold activation from control animals. The physiological consequence of severe hypoxia induced GDH phosphorylation may be to suppress GDH activity under low oxygen, shutting off this critical bridge point between two metabolic pathways. PMID- 22076535 TI - MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer. AB - MicroRNAs (miRNAs) are emerging as a class of small regulatory RNAs whose alterations are implicated in the initiation and progression of human cancers. Our study showed that miR-25 was highly expressed both in clinical ovarian cancer samples and cell lines. Down-regulation of miR-25 in ovarian cancer cells induced apoptosis whereas overexpression of miR-25 enhanced cell proliferation. The effects of miR-25 abrogation were partly mediated by the intrinsic apoptosis pathway. Many pro-apoptotic proteins such as Bim, Bax and caspase-3 were up regulated after transfection. Furthermore, luciferase assays demonstrated that Bim was the direct target of miR-25. Introducing Bim cDNA without 3'UTR abrogated miR-25-induced cell survival. Finally, there was an inverse relationship between Bim and miR-25 expression in ovarian cancer tissues. Taken together, these data indicate that miR-25 directly regulates apoptosis by targeting Bim in ovarian cancer and that miR-25 could be a potential therapeutic target for ovarian cancer intervention. PMID- 22076536 TI - Ferrofluid mediated nanocytometry. AB - We present a low-cost, flow-through nanocytometer that utilizes a colloidal suspension of non-functionalized magnetic nanoparticles for label-free manipulation and separation of microparticles. Our size-based separation is mediated by angular momentum transfer from magnetically excited ferrofluid particles to microparticles. The nanocytometer is capable of rapidly sorting and focusing two or more species, with up to 99% separation efficiency and a throughput of 3 * 10(4) particles/s per mm(2) of channel cross-section. The device is readily scalable and applicable to live cell sorting with biocompatible ferrofluids, offering competitive cytometer performance in a simple and inexpensive package. PMID- 22076537 TI - The global histone modification pattern correlates with overall survival in metachronous liver metastasis of colorectal cancer. AB - Post-translational histone modifications are known to be altered in cancer tissues, and differences in the histone modification levels have recently been used to predict the clinical outcome in patients with certain types of cancer. In this study, we evaluated the immunohistochemical staining patterns of histone H3 dimethylation and acetylation in metachronous liver metastasis of colorectal carcinomas and examined its correlation with patient prognosis. Double 2 mm core tissue microarrays were made from 54 paraffin-embedded samples of liver metastasis from colorectal adenocarcinoma, and were examined by an immunohistochemical analysis of histone H3 lysine 4 (H3K4) dimethylation, histone, H3 lysine 9 (H3K9) dimethylation and histone H3 lysine 9 (H3K9) acetylation. Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were then examined for correlations with the clinicopathological parameters and clinical outcome. Dimethylation of H3K4 correlated with the tumor histological type (P=0.043), and acetylation of H3K9 correlated with the tumor histological type (P=0.016). In addition, lower levels of H3K4 dimethylation correlated with a poor survival rate (P=0.035). The multivariate survival analysis showed that the H3K4 dimethylation status is an independent prognostic factor for colorectal cancer patients (P=0.011). We suggest that the pattern of histone modification as detected by immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas. PMID- 22076538 TI - Is octreotide treatment useful in patients with congenital chylothorax? AB - BACKGROUND: Congenital chylothorax (CC) is a severe congenital disorder characterized by the collection of chyle in the pleural space. Recent case reports suggest that the use of octreotide in the treatment of CC may be useful. OBJECTIVE: To evaluate the effect of octreotide on pleural effusions in CC. METHODS: Hospital records of 7 patients with a CC, who were admitted to the Neonatal Intensive Care Unit of the Radboud University Nijmegen Medical Centre between 2006 and 2010 and were treated with octreotide, were retrospectively evaluated. RESULTS: There was no clear and consistent effect of octreotide treatment on pleural effusions. Pleural effusions eventually decreased in all patients after reaching a dose of 5-6 MUg/kg/min, but this could also reflect the natural history of CC. Out of 7 patients, 4 were diagnosed with persistent pulmonary hypertension of the newborn. No other known side effects of octreotide were found. There was a mortality rate of 30%. CONCLUSIONS: No clear and consistent effect of octreotide was identified. Pulmonary hypertension was a common problem in this patient group. It is not clear whether or not this was caused or maintained by octreotide treatment. A randomized controlled trial is needed to investigate the safety and usefulness of octreotide. Until then, clinicians should be careful in using octreotide, especially when persistent pulmonary hypertension is present. PMID- 22076539 TI - Ischemic changes on rubidium-82 positron emission tomography imaging are associated with left ventricular functional and volumetric change independent of metabolic properties and echocardiographic functional variables in ischemic cardiomyopathy. AB - Positron emission tomography (PET) imaging allows identification of stress induced ischemia and myocardial viability in patients with ischemic cardiomyopathy. We assessed the left ventricular (LV) functional response to vasodilator stress in patients with advanced ischemic cardiomyopathy undergoing pharmacologic stress (PET) perfusion and metabolic imaging. Additionally, we aimed to determine if mitral regurgitation (MR), right ventricular (RV) dysfunction and diastolic function influenced the observed LV responses to pharmacologic stress. In 161 patients (81% men; 65 +/- 13 years), PET and echocardiography were performed within a week for noninvasive evaluation of myocardial ischemia and viability (scored using 17-segment model), as well as ventricular and valvular function. Patients were stratified based on ischemic defects in any segments versus hibernation/scar defects only. The LV volumes, EF by gating and transient ischemic dilatation (TID) index were generated automatically. Wall thickening (WT) scores were determined visually. The subgroup with reversible/ischemic segments on PET imaging (N = 55) exhibited greater end systolic (ESV) and end-diastolic volume (EDV) enlargement during stress (13 +/- 22 and 16 +/- 43 ml increase respectively, vs. 0 +/- 18 ml [P < 0.0001] and 2 +/- 24 ml [P = 0.01]), a decrease in LVEF during stress (mean -3% vs. +2%), and greater TID indices (mean 1.13 +/- 0.18 vs. 1.02 +/- 0.12) compared to hibernation/scar only (N = 92). In addition, mean WT scores during stress declined significantly only in the ischemic subgroup (P < 0.0001 for regional LAD, non-LAD and global wall thickening scores). The prevalence and the severity of MR and RV dysfunction did not differ between groups. By univariate analysis, global and LAD territory segmental ischemia, global sum stress score (SSS), TID index, resting EF, ESV enlargement during stress, as well as global WT changes correlated with post-stress LVEF decline. Multivariate predictors included SSS, resting LVEF, and ESV change. Ischemic changes on vasodilator PET imaging are associated with global LV functional decline and volumetric dilatation, presumably due to stunning effect. Severity of RV dysfunction and MR had limited impact on the above changes. PMID- 22076540 TI - Management and outcome of CSF-JC virus PCR-negative PML in a natalizumab-treated patient with MS. AB - OBJECTIVE: To describe the diagnosis and management of a 49-year-old woman with multiple sclerosis (MS) developing a progressive hemiparesis and expanding MRI lesion suspicious of progressive multifocal leukoencephalopathy (PML) 19 months after starting natalizumab. RESULTS: Polyomavirus JC (JCV)-specific qPCR in CSF was repeatedly negative, but JCV-specific antibodies indicated intrathecal production. Brain biopsy tissue taken 17 weeks after natalizumab discontinuation and plasmapheresis was positive for JCV DNA with characteristic rearrangements of the noncoding control region, but histology and immunohistochemistry were not informative except for pathologic features compatible with immune reconstitution inflammatory syndrome. A total of 22 months later, the clinical status had returned close to baseline level paralleled by marked improvement of neuroradiologic abnormalities. CONCLUSIONS: This case illustrates diagnostic challenges in the context of incomplete suppression of immune surveillance and the potential of recovery of PML associated with efficient immune function restitution. PMID- 22076541 TI - Cortical lesions in radiologically isolated syndrome. AB - OBJECTIVE: To assess the presence of cortical lesions (CLs) as detected by MRI in subjects with radiologically isolated syndrome (RIS). METHODS: Fifteen subjects with RIS underwent an MRI examination, including a double inversion recovery sequence for CL assessment. T2-hyperintense white matter (WM) lesion volume (LV) and normalized volumes of brain and cortex were also obtained. RESULTS: Thirty four CLs were identified in 6 of 15 (40%) subjects with RIS and predominantly distributed in frontotemporal lobes. CLs were frequent in subjects with RIS with immunoglobulin G oligoclonal bands on CSF, cervical cord lesions, and dissemination in time on brain MRI. WM LV was higher in subjects with CLs than in those without CLs (11.5 +/- 10.1 vs 3.9 +/- 2.8 cm(3), p = 0.04). Indeed, CL number and volume correlated with WM LV (r = 0.57, p = 0.03 and r = 0.61, p = 0.01). All subjects with CLs were classified in a previous study as having a very high probability of having relapsing-remitting multiple sclerosis (MS) on a logistic regression analysis of quantitative MRI indices. CONCLUSIONS: We found CLs in subjects with RIS, a condition characterized by the unanticipated MRI finding of WM lesions highly suggestive of MS in the absence of a clinical scenario. CLs were mainly localized to the frontotemporal lobes and were associated with important markers of evolution to MS. PMID- 22076542 TI - Increased risk of leg motor restlessness but not RLS in early Parkinson disease. AB - OBJECTIVE: This study explores the risk and correlates of leg restlessness in drug-naive patients with Parkinson disease (PD) as compared to control subjects matched for age and gender. METHODS: A total of 200 drug-naive patients with early, unmedicated PD derived from a population-based incident cohort and 173 age and gender-matched control subjects were assessed for leg restlessness by structured interviews, clinical examination, and blood samples. All subjects were Caucasian. Restless legs syndrome (RLS) was diagnosed according to the essential diagnostic criteria. RESULTS: More patients (81 of 200, 40.5%) than controls (31 of 173, 17.9%) reported leg restlessness (p < 0.001). Thirty-one (15.5%) of these patients with PD and 16 (9.2%) control subjects met RLS criteria (p = 0.07). A total of 21 (12.5%) patients and 12 (6.9%) controls with RLS remained after the exclusion of potential RLS mimics and 26 patients vs 10 control subjects with leg motor restlessness (LMR), leading to a relative risk for RLS of 1.76 (95% confidence interval [CI] 0.90-3.43, p = 0.089) and 2.84 for LMR (95% CI 1.43 5.61, p = 0.001) in PD. Except for increased sleep disturbances in patients with RLS and increased Montgomery and Asberg Depression Rating Scale scores for patients with RLS or LMR there were no other major differences in relevant blood tests, motor or cognitive function between PD with and without RLS or LMR. CONCLUSION: LMR and not RLS occurs with a near 3-fold higher risk as compared to controls in early PD. The findings underline a need for more accurate assessments of RLS in PD and support the notion that RLS and PD are different entities. PMID- 22076544 TI - Incidence of dementia in oldest-old with amnestic MCI and other cognitive impairments. AB - OBJECTIVE: To examine the incidence of dementia among the oldest-old people with normal cognition and different types of cognitive impairment. METHODS: This study included 395 participants without dementia (mean age 93.3 years) from The 90+ Study, a prospective, population-based study of aging and dementia in people aged 90 years and older. The participants had evaluations for dementia every 6 months, and their average follow-up was 2.5 years. We examined the incidence of all-cause dementia in participants stratified into 4 cognitive groups: normal, amnestic mild cognitive impairment (aMCI), nonamnestic mild cognitive impairment (naMCI), and other cognitive impairment (OCI). RESULTS: Dementia incidence was highest for participants with aMCI (31.4% per year) and OCI (39.9% per year). Participants with naMCI had an incidence of 14.1% per year, and participants with normal cognition had an incidence of 8.4% per year. Dementia incidence was associated with increasing age in both normal and cognitively impaired participants; however, an APOE4 allele was associated with a higher dementia incidence only in participants with baseline cognitive impairment. CONCLUSIONS: The risk of developing dementia in the oldest-old is high and increases to higher rates when cognitive impairment is present. Similar to results of studies in younger elderly individuals, cognitive impairment and increasing age were related to increased dementia incidence. High dementia incidence rates in the oldest-old individuals, particularly when cognitively impaired, emphasize the need to further study cognitive impairment and dementia in this rapidly expanding age group. PMID- 22076545 TI - Not all that goes "bump in the night" is RLS: leg motor restlessness in PD. PMID- 22076543 TI - Acute myeloid leukemia in Italian patients with multiple sclerosis treated with mitoxantrone. AB - OBJECTIVES: To evaluate the incidence and dose-dependency of mitoxantrone (MTX) associated acute myelocytic leukemia (AML) in the network of Italian multiple sclerosis (MS) clinics. METHODS: We performed a multicenter retrospective cohort study of patients treated with MTX in MS centers under the Italian national health care system between 1998 and 2008. Demographic, disease, treatment, and follow-up information were collected using hospital records. RESULTS: Data were available for 3,220 patients (63% women) from 40 Italian centers. Follow-up (mean +/- SD) was 49 +/- 29 months (range 12-140 months). We observed 30 cases of AML (incidence 0.93% [95% confidence interval 0.60%-1.26%]). The mean cumulative dose was higher in patients with AML (78 vs 65 mg/m(2), p = 0.028). The median interval from the start of therapy to AML diagnosis was longer than expected at 33 months (range 13-84 months); 8 patients (27%) developed AML 4 years or more after the first MTX infusion. The rate of mortality associated with AML was 37%. CONCLUSIONS: This higher than expected risk of AML and related mortality requires that treatment decisions must be made jointly between clinicians and patients who understand their prognosis, treatment options, and treatment-related risks. The now large exposed MS population must be monitored for hematologic abnormalities for at least 6 years from the end of therapy, to ensure the rapid actions needed for early diagnosis and treatment of AML. PMID- 22076546 TI - Intrathecal effects of daclizumab treatment of multiple sclerosis. AB - OBJECTIVES: We previously reported that daclizumab, a humanized monoclonal antibody against CD25, reduced contrast-enhancing lesions (CEL) in patients with multiple sclerosis (MS) who were suboptimal responders to interferon-beta and that this response correlated with expansion of CD56(bright) NK cells. These data have been reproduced in a placebo-controlled multicenter trial (CHOICE study). The current study investigates whether daclizumab monotherapy reduces CEL in untreated patients with relapsing-remitting MS (RRMS) and the effects of daclizumab on the intrathecal immune system. METHODS: Sixteen patients with RRMS with high inflammatory activity were enrolled in an open-label, baseline-vs treatment, phase II trial of daclizumab monotherapy for 54 weeks and followed by serial clinical and MRI examinations and immunologic biomarkers measured in the whole blood and CSF. RESULTS: The trial achieved predefined outcomes. There was an 87.7% reduction in brain CEL (primary) and improvements in Multiple Sclerosis Functional Composite (secondary), Scripps Neurologic Rating Scale, and Expanded Disability Status Scale (tertiary) outcomes. There was significant expansion of CD56(bright) NK cells in peripheral blood and CSF, with resultant decrease in T cells/NK cells and B cells/NK cells ratios and IL-12p40 in the CSF. Surprisingly, CD25 Tac epitope was equally blocked on the immune cells in the CSF and in peripheral blood. CONCLUSIONS: Daclizumab monotherapy inhibits formation of MS plaques in patients with RRMS and immunoregulatory NK cells may suppress activation of pathogenic immune responses directly in the CNS compartment. CLASSIFICATION OF EVIDENCE: The study provides Class III evidence that daclizumab reduces the number of contrast-enhancing lesions in treatment-naive patients with RRMS over a 54-week period. PMID- 22076547 TI - The manifold faces of PML and the challenge of diagnosis. PMID- 22076548 TI - Spinal subtraction MRI for diagnosis of epidural leakage in SIH. AB - OBJECTIVE: To explore the efficacy of spinal MRI study with subtraction analysis as a rapid, reliable, and noninvasive procedure to detect epidural CSF collection in spontaneous intracranial hypotension (SIH) syndrome. METHODS: Seventeen patients (mean age 42 years, age range 17-65 years; 11 female) with SIH diagnosed using the International Classification of Headache Disorders criteria and 13 age matched control subjects underwent standard sagittal spinal MRI. Postprocessing image analysis with subtraction of T1-weighted from T2-weighted MRI scans was performed and tested for the detection of the CSF leak. RESULTS: The CSF epidural collection was visible in all patients with SIH and was detected at the dorsal (16 of 17), cervical (13 of 17), lumbar (13 of 17), and sacral (12 of 17) levels. None of the control subjects showed a CSF leak. Diverticula were present in 23% of patients, whereas the actual site of the CSF leak was recognized in only one patient. Eight patients were treated conservatively, whereas 9 patients required an epidural blood patch, performed at a fixed L2-L3 or L3-L4 spinal level, with complete recovery. CONCLUSIONS: Spinal MRI with dedicated subtraction analysis could represent the first-line diagnostic tool in the management of patients with SIH, thus leaving invasive investigation for selected patients, such those requiring dural surgery. PMID- 22076549 TI - Clinical characteristics of pediatric-onset neuro-Behcet disease. AB - OBJECTIVES: Neurologic involvement in the pediatric population with Behcet disease (BD) is limited to case reports. The aim of this study is to examine the frequency and type of neurologic involvement in pediatric patients with BD. METHODS: Medical records of 728 patients with a diagnosis of neuro-BD (NBD) of 2 large BD cohorts followed in Istanbul University were included in the study. Patients with an onset of both systemic and neurologic symptoms at or before age 16 (pediatric neuro-BD) were identified. Demographic and clinical characteristics of pediatric patients with NBD were compared with adult patients with NBD. RESULTS: There were 26 cases with pediatric BD (3.6%) and 702 (96.4%) adult-onset patients. Gender ratio was equal in the general pediatric BD cohort, whereas male/female ratio was 5.5/1 in pediatric NBD cases. Mean age at BD onset and neurologic involvement onset were 13.0 +/- 3.0 and 13.5 +/- 2.4, respectively, and in the adult population mean age at onset of BD was 26.7 +/- 8.0 and neurologic involvement occurred a mean of 5.3 +/- 4.5 years later. Clinical and MRI evaluation revealed that 3 children had CNS parenchymal involvement and 23 had dural venous sinus thrombosis (88.5%). We observed parenchymal involvement in 74.8% of the adults, contrary to the low 17.2% of cases with venous sinus thrombosis. CONCLUSIONS: Pediatric NBD comprises 3.6% of our whole NBD cohort, with a male predominance, mainly in the form of dural venous sinus thrombosis, whereas in the adult NBD population the dominant form of neurologic involvement is parenchymal, suggesting that the pathogenesis of NBD may be different according to the age at disease onset. PMID- 22076550 TI - Evaluation of various cytokines elicited during antigen-specific recall as potential risk indicators for the differential development of leprosy. AB - Leprosy is a dermato-neurological disease caused by Mycobacterium leprae infection that manifests across a wide range of clinical and immunological outcomes. Diagnosis is still currently based on clinical manifestations and simple tests are needed. This study investigated whether biomarkers induced by defined M. leprae proteins in 24-h whole blood assays (WBA) could discriminate active leprosy patients from at-risk contacts. Newly diagnosed, untreated paucibacillary (PB; tuberculoid leprosy/borderline tuberculoid [TT/BT]) and multibacillary (MB; borderline lepromatous/lepromatous leprosy [BL/LL]) leprosy patients, as well as healthy household contacts (HHC) of MB patients, were recruited in central western Brazil (Goiania/Goias). Cell-based responses to the ML0276, ML1623, ML0405, ML1632, 92f, and ML1011 antigens were measured by Luminex 14-plex assays detecting eotaxin, IFNgamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL 12p70, IL-15, IL-17A, IL-23, IL-31, IP-10, and TNFalpha. Our data reinforce that IFNgamma is currently the best indicator of the antigen-specific cellular immune response of TT/BT leprosy and demonstrate that the same antigens promote the secretion of IL-4 in blood from BL/LL leprosy patients. While none of the biomarkers tested could discriminate leprosy patients from HHC, our data indicate that, although most HHC antigen-specific responses are qualitatively similar to TT/BT patients, some HHC can respond similarly to BL/LL patients. PMID- 22076551 TI - Are enterococci playing a role in postoperative peritonitis in critically ill patients? AB - This prospective non-interventional study is aimed at evaluating the role of enterococci in the postoperative course of postoperative peritonitis (POP) and the predictive factors for isolating Enterococcus spp. All adult patients, hospitalized in intensive care, who had POP between September 2006 and February 2010 were analysed. The patients' baseline clinical characteristics and microbiological and surgical characteristics of the first episode of POP were recorded. The rates of surgical and non-surgical complications and mortality were studied. A total of 139 patients were analysed and Enterococcus spp. were recovered in 61 patients (43%). The presence of enterococci was associated with significantly more intra-abdominal abscesses (26% vs 12%, p=0.025), but did not affect the rate of reoperation or mortality. Antibiotic use before reoperation was the only independent predictive factor for isolating enterococci (OR=2.19, CI95%: 1.02-4.70, p<0.043). Although mortality was not affected by the presence of Enterococcus spp., a higher rate of intra-abdominal abscess was found, suggesting that enterococci play a significant role in postoperative peritonitis, but the need to treat them remains to be determined. Previous antibiotic use before reoperation was a key factor in predicting the subsequent recovery of enterococci. PMID- 22076552 TI - Alternative energy input: mechanochemical, microwave and ultrasound-assisted organic synthesis. AB - Microwave, ultrasound, sunlight and mechanochemical mixing can be used to augment conventional laboratory techniques. By applying these alternative means of activation, a number of chemical transformations have been achieved thereby improving many existing protocols with superior results when compared to reactions performed under traditional conditions. The purpose of this critical review is to highlight the advances in this general area by presenting such newer applications in organic synthesis (175 references). PMID- 22076553 TI - Involvement of concentrative nucleoside transporter 1 in intestinal absorption of trifluorothymidine, a novel antitumor nucleoside, in rats. AB - alphaalphaalpha-Trifluorothymidine (TFT), an anticancer nucleoside analog, is a potent thymidylate synthase inhibitor. TFT exerts its antitumor activity primarily by inducing DNA fragmentation after incorporation of the triphosphate form of TFT into the DNA. Although an oral combination of TFT and a thymidine phosphorylase inhibitor has been clinically developed, there is little information regarding TFT absorption. Therefore, we investigated TFT absorption in the rat small intestine. After oral administration of TFT in rats, more than 75% of the TFT was absorbed. To identify the uptake transport system, uptake studies were conducted by using everted sacs prepared from rat small intestines. TFT uptake was saturable, significantly reduced under Na(+)-free conditions, and strongly inhibited by the addition of an endogenous pyrimidine nucleoside. From these results, we suggested the involvement of concentrative nucleoside transporters (CNTs) in TFT absorption into rat small intestine. In rat small intestines, the mRNAs coding for rat CNT1 (rCNT1) and rCNT2, but not for rCNT3, were predominantly expressed. To investigate the roles of rCNT1 and rCNT2 in TFT uptake, we conducted uptake assays by using Xenopus laevis oocytes injected with rCNT1 complementary RNA (cRNA) and rCNT2 cRNA. TFT uptake by X. laevis oocytes injected with rCNT1 cRNA, and not rCNT2 cRNA, was significantly greater than that by water-injected oocytes. In addition, in situ single-pass perfusion experiments performed using rat jejunum regions showed that thymidine, a substrate for CNT1, strongly inhibited TFT uptake. In conclusion, TFT is absorbed via rCNT1 in the intestinal lumen in rats. PMID- 22076554 TI - Change in self-efficacy, autonomous and controlled motivation predicting smoking. AB - Although motivational interviewing (MI) has been shown to be effective in changing health behaviors, its effects on smoking cessation have been mixed. The purpose of the present study is to assess factors of motivation and self-efficacy as they mediate the relationship between MI and smoking cessation. This is a secondary analysis of an MI based smoking cessation randomized trial. MI counseling was associated with change in smoking behaviors during a 12 months intervention but was not related to autonomous motivation, controlled motivation, or self-efficacy at baseline and 6 months, the hypothesized mediators. This study confirmed the pathway to quit smoking through increase in self-efficacy. PMID- 22076555 TI - Cationic nanomicelles for delivery of plasmids encoding interleukin-4 and interleukin-10 for prevention of autoimmune diabetes in mice. AB - PURPOSE: To evaluate the in vivo transfection efficiency of N-acyl derivatives of low-molecular weight chitosan (LMWC) to deliver pVIVO2-mIL4-mIL10 plasmid encoding interleukin-4 (IL-4) and interleukin-10 (IL-10) in multiple, low-dose streptozotocin induced diabetic mouse model. METHODS: N-acyl LMWC nanomicelles were characterized for size and charge. The pVIVO2-mIL4-mIL10/N-acyl LMWC polyplexes were injected intramuscularly in mice and compared for transfection efficiency with naked DNA and FuGENE(r) HD. Bicistronic pVIVO2-mIL4-mIL10 plasmid was compared with individual plasmids encoding IL-4 and IL-10 for efficacy. The levels of blood glucose and serum IL-4, IL-10, TNF-alpha and IFN-gamma were monitored. The ability of plasmid administration to protect from insulitis and biocompatibility of N-acyl LMWC were studied. RESULTS: The N-acyl LMWC led to significantly higher (p < 0.05) expression of IL-4 and IL-10 and reduced the levels of blood glucose, TNF-alpha and IFN-gamma, especially in animals treated with pVIVO2-mIL4-mIL10 plasmid. The pancreas of pDNA/N-acyl LMWC polyplex treated animals exhibited protection from insulitis and the delivery systems were found to be biocompatible. CONCLUSIONS: N-acyl derivatives of LMWC are efficient and biocompatible gene delivery vectors, and the administration of bicistronic pVIVO2 mIL4-mIL10 plasmid polyplexes can protect the pancreatic islets from insulitis, possibly due to the synergistic effect of IL-4 and IL-10 encoding plasmids. PMID- 22076557 TI - Mucosal immunology: the 'AHR diet' for mucosal homeostasis. PMID- 22076556 TI - Towards a systems understanding of MHC class I and MHC class II antigen presentation. AB - The molecular details of antigen processing and presentation by MHC class I and class II molecules have been studied extensively for almost three decades. Although the basic principles of these processes were laid out approximately 10 years ago, the recent years have revealed many details and provided new insights into their control and specificity. MHC molecules use various biochemical reactions to achieve successful presentation of antigenic fragments to the immune system. Here we present a timely evaluation of the biology of antigen presentation and a survey of issues that are considered unresolved. The continuing flow of new details into our understanding of the biology of MHC class I and class II antigen presentation builds a system involving several cell biological processes, which is discussed in this Review. PMID- 22076559 TI - Autoimmunity: Linking commensals with autoimmunity. PMID- 22076558 TI - Peptidoglycan recognition proteins: modulators of the microbiome and inflammation. AB - All animals, including humans, live in symbiotic association with microorganisms. The immune system accommodates host colonization by the microbiota, maintains microbiota-host homeostasis and defends against pathogens. This Review analyses how one family of antibacterial pattern recognition molecules - the peptidoglycan recognition proteins - has evolved a fascinating variety of mechanisms to control host interactions with mutualistic, commensal and parasitic microorganisms to benefit both invertebrate and vertebrate hosts. PMID- 22076560 TI - Novel role of c-jun N-terminal kinase in regulating the initiation of cap dependent translation. AB - Initiation of protein translation by the 5' mRNA cap is a tightly regulated step in cell growth and proliferation. Aberrant activation of cap-dependent translation is a hallmark of many cancers including non-small cell lung cancer. The canonical signaling mechanisms leading to translation initiation include activation of the Akt/mTOR pathway in response to the presence of nutrients and growth factors. We have previously observed that inhibition of c-jun N-terminal kinase (JNK) leads to inactivation of cap-dependent translation in mesothelioma cells. Since JNK is involved in the genesis of non-small cell lung cancer (NSCLC), we hypothesized that JNK could also be involved in activating cap dependent translation in NSCLC cells and could represent an alternative pathway regulating translation. In a series of NSCLC cell lines, inhibition of JNK using SP600125 resulted in inhibition of 4E-BP1 phosphorylation and a decrease in formation of the cap-dependent translation complex, eIF4F. Furthermore, we show that JNK-mediated inhibition of translation is independent of mTOR. Our data provide evidence that JNK is involved in the regulation of translation and has potential as a therapeutic target in NSCLC. PMID- 22076561 TI - Clinical trials during pregnancy: what has been done. AB - OBJECTIVE: We describe clinical trials conducted in pregnant women. METHODS: We searched PubMed database for articles related to clinical trials between 01/01/2000 and 31/12/2009 involving pregnant women by using the preferred terms "pregnancy", "human", and "clinical trials". RESULTS: Of 1,264 retrieved publications, 762 (60%) were excluded, leaving 502 for analysis: 53% were preventive studies in maternal or fetal conditions; 47% were therapeutic trials, mostly focused on acute obstetric diseases; 66% were assigned a pharmacological intervention. The studied drugs were 16% for labour induction and 15% for abortive procedures, followed by multivitamins and micronutrients, labour analgesia and anesthesia, antibiotics, tocolytics, and antimalarial drugs. The main objectives of the studies were focused on efficacy (54%) and efficacy and safety (26%); 81% of the studies were controlled, randomized and parallel-design trials; 19% were blinded. CONCLUSION: Clinical trials in pregnant women are mainly conducted with an efficacy objective regarding maternal-fetal prevention and in obstetric diseases to study labor induction and abortive measures. This is in line with the type of intervention and drugs involved. PMID- 22076562 TI - Evaluation of lansoprazole as a probe for assessing cytochrome P450 2C19 activity and genotype-phenotype correlation in childhood. AB - PURPOSE: Lansoprazole, a cytochrome P450 2C19 (CYP2C19) substrate, has been widely used in children to manage acid-related diseases. CYP2C19 exhibits marked genetic polymorphisms, and distribution of these polymorphisms varies among different ethnic groups. There is limited data regarding the use of probe drugs for determining CYP2C19 activity in children. The aim of this study was to evaluate lansoprazole as an in vivo phenotyping probe for assessing CYP2C19 activity in children. METHODS: The CYP2C19*2, *3, and *17 variants were determined in 244 children. Three hours after a single oral dose of lansoprazole (n = 94) or omeprazole (n = 19), plasma lansoprazole and 5-hydroxy lansoprazole or omeprazole and 5-hydroxy omeprazole concentrations were analyzed by high performance liquid chromatography. RESULTS: The CYP2C19*17 was the most frequent variant allele (24.4%). The group of patients with CYP2C19*17*17 genotype had a 70% lower (p < 0.05) mean lansoprazole plasma concentration compared with the CYP2C19*1*1 genotype group, whereas the CYP2C19*2*2 group had 6.9-fold higher (p < 0.01) mean lansoprazole plasma concentration. Lansoprazole metabolic ratios (lansoprazole/5-hydroxy-lansoprazole) were found to be significantly lower in the *17*17 [mean +/- standard deviation (SD); 2.8 +/- 2.1] group and higher in the *2*2 group (63.5 +/- 12.2) compared with that of the *1*1 genotype group (6.1 +/- 4.5). CONCLUSION: According to our results from a Turkish pediatric population, lansoprazole is a suitable probe drug for phenotyping CYP2C19. The CYP2C19*2 and *17 variants should be taken into consideration in predicting the clinical outcome of therapy with lansoprazole in the pediatric population. PMID- 22076563 TI - Synergistic effects of octylphenol and isobutyl paraben on the expression of calbindin-D9k in GH3 rat pituitary cells. AB - Endocrine disruptors (EDs) have estrogenic activity and can cause physiological estrogenic responses. Octylphenol (OP) is one of the alkylphenolic compounds known as environmental xenoestrogens because they strongly compete with endogenous estrogens to bind to estrogen receptors (ERs). Isobutyl paraben (IBP), a widely used preservative, also exhibits estrogenic activity. Calbindin-D9k (CaBP-9k) is a novel biomarker for the detection of EDs used in our previous studies. In this study, the CaBP-9k gene was utilized as a marker for the estrogenic activity of combined OP and IBP to investigate possible additive, synergistic or antagonistic effects of these compounds in GH3 rat pituitary cells. GH3 cells were treated with different individual or combined doses of OP and IBP. In addition, the antiestrogen ICI 182,780 was used to examine the potential involvement of ERs in the induction of CaBP-9k expression by EDs. It was found that CaBP-9k expression was significantly increased at a high-dose of OP (1 uM) combined with each dose of IBP (0.1, 1 or 10 uM) compared to all single doses of IBP and OP. A synergistic increase in luciferase activity and CaBP-9k expression was observed following combination treatment with OP and IBP. Expression of the progesterone receptor (PR) gene was similarly induced by combined treatment with OP and IBP. In addition, pre-treatment with ICI 182,780, an estrogen antagonist, significantly blunted ED-induced CaBP-9k and PR expression. In summary, the expression of CaBP-9k and PR was induced more potently by combined OP and IBP than by treatment with either ED alone. ICI 182,780 treatment reversed ED-induced CaBP-9k and PR expression in these cells. Taken together, these results indicate that combined exposure to OP and IBP has a synergistic effect on the induction of CaBP-9k and PR gene expression via an ER dependent pathway in GH3 cells. PMID- 22076564 TI - Recurrences after surgical resection of intraductal papillary mucinous neoplasm of the pancreas: a single-center study of recurrence predictive factors. AB - OBJECTIVE: The detection of intraductal papillary mucinous neoplasms (IPMN) has increased over the last decade, but still, management remains controversial. The main problems are their potential for malignancy and risk of recurrence. The purpose of this study was to determine the predictive factors of recurrence after surgical resection. METHODS: All patients with IPMN who underwent pancreatectomy with curative intent were considered. Data were collected from a prospective base. RESULTS: From 1994 to 2009, 104 patients underwent pancreatectomy. Twenty one (20%) had recurrence, 15 on remnant pancreas (none on pancreatic cut surface) and 6 with distant metastases. Twelve patients had total pancreatectomy (1 awaiting surgery). Thirteen (38.2%) of 34 patients with invasive IPMN and 20 (25.9%) of 77 with main duct involvement (including combined type) had recurrence. In univariate analysis, American Society of Anesthesiologist score and histological and duct type had a significant impact on recurrence rate. In multivariate analysis, histological type (invasiveness) was the only significant predictive factor for recurrence. CONCLUSION: The risk of recurrence of IPMN after resection depends on the histological type. According to surgical margin, invasiveness, and the type of duct involved, we identified a high-risk group with invasive main duct lesion and a low-risk group with noninvasive branch duct lesion. PMID- 22076565 TI - The neurotransmitter ATP triggers Ca2+ responses promoting coordination of pancreatic islet oscillations. AB - OBJECTIVES: Pulsatile insulin release into the portal vein is critically dependent on entrainment of the islets in the pancreas into a common oscillatory phase. Because the pulses reflect periodic variations of the cytoplasmic Ca concentration ([Ca]i), we studied whether the neurotransmitters adenosine triphosphate (ATP) and acetylcholine promote synchronization of [Ca]i oscillations between islets lacking contact. METHODS: Medium-sized and small mouse islets and cell aggregates were used for measuring [Ca]i with the indicator fura-2. RESULTS: Exposure to acetylcholine resulted in an initial [Ca]i peak followed by disappearance of the [Ca]i oscillations induced by 11-mmol/L glucose. The effect of ATP was often restricted to an elusive [Ca]i peak. The incidence of distinct [Ca]i responses to ATP increased under conditions (accelerated superfusion, small islets, or cell aggregates) intended to counteract purinoceptor desensitization owing to intercellular accumulation of ATP. Attempts to imitate neural activity by brief (15 seconds) exposure to ATP or acetylcholine resulted in temporary synchronization of the glucose-induced [Ca]i oscillations between islets lacking contact. CONCLUSIONS: The data support the idea that purinergic signaling has a key role for coordinating the oscillatory activity of the islets in the pancreas, reinforcing previous arguments for the involvement of nonadrenergic, noncholinergic neurons. PMID- 22076566 TI - Mitomycin C treatment significantly reduces central damage of islets in culture. AB - OBJECTIVES: We recently reported that mitomycin C (MMC) treatment and subsequent culture of islets significantly prolongs graft survival in allotransplantation and xenotransplantation models. The present study was performed to determine the changes in morphology and signal transduction in pancreatic islets after MMC treatment. METHODS: Freshly isolated rat islets were treated with 10 MUg/mL MMC for 30 minutes and then cultured for up to 3 days. The samples were processed for immunohistologic studies and electron microscopic examination at various times after treatment. A DNA fragmentation assay was performed to detect apoptotic cell death. Western blotting was performed to determine the effects of MMC on signal transduction. RESULTS: As early as 4 hours after culture, the islets showed central damage; most cells were necrotic and stained with anti-high mobility group box 1 antibody, and a few were apoptotic. The ratio of the damaged area to the whole area was significantly decreased after MMC treatment. Western blotting showed that MMC treatment increased the levels of activated forms of p53 and p21, whereas levels of the activated forms of Akt and caspase-3 were unchanged. CONCLUSIONS: Mitomycin C treatment protects islets from the progression of central damage during culture. The p53-p21 pathway might be involved in these effects. ABBREVIATIONS: MMC - mitomycin C, HMGB1 - high mobility group box 1. PMID- 22076567 TI - Proteomic assessment of markers for malignancy in the mucus of intraductal papillary mucinous neoplasms of the pancreas. AB - OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas evolve from dysplasia to invasive adenocarcinoma. The aims of this study were to look for candidate protein profiles in IPMN mucus according to histological grade, using a differential proteomic technique, and to highlight protein peaks associated with malignant transformation. METHODS: Forty-three mucus samples obtained from surgically resected IPMN and categorized as benign (low/moderate dysplasia) or malignant (severe dysplasia/invasive adenocarcinoma) in 21 and 22 patients, respectively. A surface-enhanced laser desorption ionization time-of flight mass spectrometry was used to determine candidate protein expression profiles. Protein peaks that significantly differed between benign/malignant IPMN (area under curve > 0.88; P < 10; high intensity) were identified using adapted software. RESULTS: Among 952 protein peaks, 31 were differentially expressed in benign/malignant IPMN (P < 0.001). Among them, 5 candidate proteins of interest (mass-to-charge ratio [m/z]: 5217, 6326, 6719, 10,453, and 10,849 d) were selected by their high diagnostic accuracy and ability to distinguish between malignant and benign tumors. No correlation was found between peak profiles and duct involvement. CONCLUSIONS: Carcinogenic process in IPMN is associated with changes in mucus proteome with characteristic peaks that could be potential candidate biomarkers of malignancy. ABBREVIATIONS: IPMN - intraductal papillary mucinous neoplasm, EPC - extrapancreatic cancer, MRI - magnetic resonance imaging, ERCP - endoscopic retrograde cholangiopancreatography. PMID- 22076568 TI - Combination of hedgehog signaling blockage and chemotherapy leads to tumor reduction in pancreatic adenocarcinomas. AB - OBJECTIVES: Activation of the hedgehog signal transduction pathway, triggered by hedgehog binding to the transmembrane receptor patched 1 (PTCH1) or by mutations in the PTCH1 gene, plays an important role in the development of various tumors. METHODS: To investigate whether the Hedgehog signaling pathway is also active in human pancreatic adenocarcinomas, we determined the expression levels of the known Hedgehog target genes PTCH1 and GLI-1 in pancreatic tumors. To determine whether alterations in the PTCH1 gene are responsible for this pathway activation, we screened pancreatic carcinomas for mutations in PTCH. To investigate the contribution of hedgehog signaling to the tumorigenicity of pancreatic tumor cells, we blocked the Hedgehog pathway in cultured tumor cells and xenografts using the steroidal alkaloid cyclopamine and the small-molecule Hedgehog inhibitor Hh-Antag. RESULTS: We identified single nucleotide polymorphisms (SNPs) within the PTCH1 gene but no somatic PTCH1 mutations. Pathway-blockage resulted in a significant dose-dependent reduction of tumor cell growth in vitro and in vivo. Moreover, combined treatment with cyclopamine and the conventional antimetabolite gemcitabine revealed a synergistic effect on the reduction of tumor growth in pancreatic adenocarcinoma xenografts. CONCLUSIONS: Inhibition of Hedgehog signaling could be a promising approach for the treatment of pancreatic adenocarcinomas. PMID- 22076570 TI - Amide temperature coefficients in the protein G B1 domain. AB - Temperature coefficients have been measured for backbone amide (1)H and (15)N nuclei in the B1 domain of protein G (GB1), using temperatures in the range 283 313 K, and pH values from 2.0 to 9.0. Many nuclei display pH-dependent coefficients, which were fitted to one or two pK(a) values. (1)H coefficients showed the expected behaviour, in that hydrogen-bonded amides have less negative values, but for those amides involved in strong hydrogen bonds in regular secondary structure there is a negative correlation between strength of hydrogen bond and size of temperature coefficient. The best correlation to temperature coefficient is with secondary shift, indicative of a very approximately uniform thermal expansion. The largest pH-dependent changes in coefficient are for amides in loops adjacent to sidechain hydrogen bonds rather than the amides involved directly in hydrogen bonds, indicating that the biggest determinant of the temperature coefficient is temperature-dependent loss of structure, not hydrogen bonding. Amide (15)N coefficients have no clear relationship with structure. PMID- 22076569 TI - Activation of the BMP4 pathway and early expression of CDX2 characterize non specialized columnar metaplasia in a human model of Barrett's esophagus. AB - BACKGROUND: A human model of gastroesophageal reflux disease was used to examine the contribution of a non-specialized columnar type of metaplasia (NSCM) and key molecular events (BMP4 and CDX2) in the development of Barrett's esophagus. METHODS: Biopsies of the remnant esophagus from 18 patients undergoing esophagectomy with gastric preservation were taken at 6-36-month intervals postoperatively and examined for activation of the BMP pathway (BMP4/P-Smad 1/5/8) and CDX2 and CDX1 expression by imunohistochemistry, quantitative real time PCR, Western blot, and in situ hybridization. RESULTS: A short segment (mean 15.6 mm) of NSCM was detected in 10 (56%) patients, with an increasing prevalence from 17% at 6 months to 62% at 36 months. Nuclear expression of P-Smad 1/5/8 in the squamous epithelium close to the anastomosis with strong expression in all epithelial cells of NSCM areas was found. Forty-eight (63%) biopsies with NSCM showed scattered nuclear expression of CDX2. Two cases showed isolated glands at 18, 24, and 36 months that fully expressed CDX2 and co-expressed CDX1. BMP4 mRNA and CDX2 mRNA levels were significantly greater in NSCM than in squamous epithelium. CONCLUSIONS: BMP4 activation in NSCM and early expression of CDX2 are involved in the columnar epithelial differentiation of Barrett's esophagus. PMID- 22076571 TI - A vector design that allows fast and convenient production of differently tagged proteins. AB - Recombinant-tagged proteins have a widespread use in experimental research as well as in clinical diagnostic and therapeutic approaches. Well-stocked sets of differently tagged variants of a same protein would be of great help. However, the construction of differently tagging vectors is a demanding task since cloning procedures need several tailored DNA inserts. In this study, we describe a novel vector system that allows a cost- and time-effective production of differently tagged variants of a same protein by using the same DNA fragment and a set of vectors each carrying a different tag. The design of these expression vectors is based on an intronic region that becomes functional upon cloning the insert sequence, splicing of which attaches a certain tag to the protein termini. This strategy allows for the cloning of the fragment that codes for the protein of interest, without any further modification, into different vectors, previously built and ready-to-use, each carrying a tag that will be joined to the protein. Proof of principle for our expression system, presented here, is shown through the production of a functional anti-GD2 Fab fragment tagged with biotin or polyhistidine, or a combination of both, followed by the demonstration of the functional competencies of both the protein and the tags. PMID- 22076572 TI - Scleral buckling with a non-contact wide-angle viewing system. AB - PURPOSE: To assess the outcome of scleral buckling surgery using a non-contact wide-angle viewing system for fundus visualization in patients with rhegmatogenous retinal detachment without proliferative vitreoretinopathy. PATIENTS AND METHODS: Sixteen eyes of 16 patients underwent scleral buckling using a non-contact wide-angle viewing system combined with a 25-gauge illumination fibre inserted into the sclera at the pars plana. RESULTS: The mean age of the patients was 53.6 +/- 13.7 years and the mean follow-up time was 13.4 +/- 2.8 months. Retinal reattachment was achieved in 13 of the 16 eyes (81%). Three eyes underwent vitrectomy with silicone oil injection because of development of proliferative vitreoretinopathy in 2 eyes and scleral perforation due to excessive indentation during cryoretinopexy in 1 eye. Two eyes developed limited subretinal haemorrhage during subretinal fluid drainage. CONCLUSION: Simultaneous use of a non-contact wide-angle viewing system combined with a 25 gauge light fibre illumination for fundus visualization brings the advantages of microsurgery and indirect ophthalmoscopy into scleral buckling surgery. PMID- 22076573 TI - Clinicopathologic outcomes of curative resection for sarcomatoid carcinoma of the lung. AB - OBJECTIVES: Sarcomatoid carcinoma of the lung is a very rare and aggressive subtype of non-small cell lung cancer. We explored the clinicopathologic characteristics and surgical outcome of this tumor. METHODS: Among 4,212 patients who underwent curative resection for non-small cell lung cancer from September 1994 to December 2009, 99 patients had sarcomatoid carcinoma. Medical records of patients were reviewed retrospectively. RESULTS: The mean follow-up period was 16.07 months. Thirty-six patients had pathologic stage I disease, and 63 had more advanced disease. Surgery included 2 wedge resections, 67 lobectomies, 17 bilobectomies, and 13 pneumonectomies. There were 90 pleomorphic carcinomas, 6 spindle cell carcinomas, 1 giant cell carcinoma, 1 carcinosarcoma, and 1 pulmonary blastoma. Overall 5-year survival was 54.3%. Forty-three patients experienced recurrence and 42 of these died of the cancer. Pathologic T stage as defined by the 7th TNM staging system was significantly associated with survival and recurrence (p = 0.004 and 0.002, respectively). Mean positron emission tomography uptake was significantly higher than in other types of lung cancer (p < 0.0001). CONCLUSIONS: Our results implied that surgery for sarcomatoid carcinoma must be carefully planned after extensive preoperative evaluation. Efforts should be made for accurate preoperative histological diagnosis of large peripheral tumor with exceedingly high positron emission tomography uptake. PMID- 22076574 TI - A case of severe aortic stenosis with severe coronary artery disease that was successfully treated by balloon aortic valvuloplasty and percutaneous coronary intervention. AB - We describe an 85-year-old woman with severe aortic stenosis, who also had severe coronary artery disease. She suffered from dyspnea on exertion and frequent syncope. Echocardiography revealed an immobile and heavily calcified aortic valve, and coronary angiography revealed two-vessel disease including chronic total occlusion. Open-heart surgery was refused and she was referred to our department. She underwent percutaneous coronary intervention (PCI) for the right coronary artery and left anterior descending artery. Following PCI, percutaneous balloon aortic valvuloplasty (BAV) was performed on the same day. We chose balloons of 15 * 60 mm, 18 * 60 mm, and 20 * 60 mm, respectively. Improvement in the mean aortic valve pressure gradient (PG) and calculated aortic valve area (mean PG 48-23 mmHg, 0.8-1.2 cm(2), respectively) was observed after the final balloon dilatation. No significant complications occurred. The combination of BAV with PCI may be a useful treatment for relief of the associated symptoms of severe aortic stenosis and coronary artery disease, though it does not improve the long-term prognosis. PMID- 22076576 TI - Current therapies in the management of systolic and diastolic dysfunction. AB - Heart failure, especially caused by systolic dysfunction, is the most common cause of hospitalization in the elderly population and the annual expenditure required for its management is at least $10 billion. The critical care nurse can play an active role in recognizing the differences between systolic and diastolic dysfunction, and teaching the patient and family that improper management or underuse of therapies can lead to disease progression. PMID- 22076575 TI - EGCG ameliorates the suppression of long-term potentiation induced by ischemia at the Schaffer collateral-CA1 synapse in the rat. AB - The function of Epigallocatechin gallate (EGCG), a main component of green tea, has been widely investigated, amelioration of synaptic transmission and neuroprotective effects against ischemia-induced brain damage among others. However, the mechanism underlying is still unveiled. We investigated the effects of EGCG on high frequency stimulation-induced long-term potentiation (LTP) in the Schaffer collateral-CA1 synapse with or without cerebral ischemia injury induced by middle cerebral artery occlusion (MCAO) in vivo to examine the possible relations between EGCG and synaptic transmission. Application of EGCG modulated synaptic transmission and produced a dose-dependent improvement of the induction of LTP. However, relative high-dose EGCG can block the induction of LTP at the Schaffer collateral-CA1 synapse in normal rat in vivo. In addition, the effects of EGCG were observed on the infarct volume and neurological deficit in rats subjected to MCAO; furthermore, the cell viability of primary cultured rat hippocampal and cortical neurons suffered from oxygen-glucose deprivation were evaluated with MTT and LDH assay, which showed significant neuroprotective properties in vitro. Surprisingly, the contents of the glutamate (Glu), glycine (Gly), and gamma-aminobutyric acid amino acids were totally disequilibrated before and after cerebral ischemia injury and could be rebalanced to original level by application of EGCG. Our results suggest that EGCG is able to improve the efficiency of synaptic transmission in cerebral ischemia injury with attenuated effect related to the neuroprotection of EGCG through regulating excitatory and inhibitory amino acid balance. PMID- 22076579 TI - Dealing with coagulopathies of pregnancy-induced hypertension. AB - A woman with pregnancy-induced hypertension may experience a potentially fatal bleeding disorder. This article describes how to recognize trouble and intervene appropriately. PMID- 22076580 TI - Tenecteplase: a promising new fibrinolytic agent. AB - Acute coronary syndrome can mean anything from unstable angina to acute myocardial infarction (MI) with ST-segment elevation. Tenecteplase, a new fibrinolytic agent used to treat ST-segment elevation acute MI, has some advantages over other fibrinolytic agents. This article describes tenecteplase's actions, indications, contraindications, and use. PMID- 22076581 TI - Communicating to get results: an interview with Jacob Weisberg. AB - An expert describes ways to improve communication skills and save time, solve problems, and motivate employees. PMID- 22076582 TI - Malnutrition in the elderly: what nurses need to know. AB - Identifying nutritional deficit vulnerability and early and advanced malnutrition states in the elderly can be challenging. This article provides a clinical evaluation guide for identifying risks and diagnosing incipient and advanced malnutrition. Diagnosis and intervention can prevent loss of function and independence and decrease morbidity and mortality in the elderly. PMID- 22076583 TI - Braced for disaster. AB - Organized disaster or mass casualty incident planning is typically limited to prehospital, emergency department, operating room, and intensive care unit personnel. Such planning can be transferred to acute care situations as well. PMID- 22076584 TI - Measuring "hang time": contamination of intra-arterial flush solutions over time. AB - This study reports on improved patient care through procedures that reduce the likelihood of hospital-acquired infections. This investigation found that longer "hang times" for nurse-prepared intra-arterial flush solutions did not significantly increase the patient's risk of infection. In addition, the article details cost savings and procedures to better manage nurses' time. PMID- 22076585 TI - Bioterrorism: the new threat. PMID- 22076586 TI - Enhancement of cytotoxic and pro-apoptotic effects of 2-aminophenoxazine-3-one on the rat hepatocellular carcinoma cell line dRLh-84, the human hepatocellular carcinoma cell line HepG2, and the rat normal hepatocellular cell line RLN-10 in combination with 2-deoxy-D-glucose. AB - The cytotoxic and pro-apoptotic effects of a single dose of 2-aminophenoxazine-3 one (Phx-3) or 2-deoxyglucose (2-DG) or of a combined dose of Phx-3 and 2-DG were studied in the rat hepatocellular carcinoma cell line dRLh-84, the human hepatocellular carcinoma cell line HepG2 and the rat normal hepatocellular cell line RLN-10. The number of viable cells decreased in a dose-dependent manner, when dRLh-84, HepG2 or RLN-10 cells were treated with 2-DG (0.5-20 mM) or Phx-3 (1-50 uM) alone at 37C for 48 h. When these cells were treated with 10 mM 2-DG and different concentrations of Phx-3, the number of viable cells decreased dose dependently and in an additive manner for these agents. A single dose of 2 or 10 uM Phx-3 induced apoptotic morphology characterized by nuclear condensation and cell shrinkage in dRLh-84, HepG2 and RLN-10 cells, while a single dose of 10 mM 2 DG did not. When Phx-3 (2 or 10 uM) treatment was combined with 2-DG (10 mM) treatment in these three cell lines, the cells with apoptotic morphology increased extensively, which was confirmed by flow cytometric analysis. In addition, autophagic morphology characterized by cytosolic vacuole formation was significantly increased in the hepatocellular carcinoma cell lines dRLh-84 and HepG2 but not in the normal hepatocellular cell line RLN-10 after a single dose of Phx-3 or 2-DG or a combined dose of Phx-3 and 2-DG. Furthermore, when dRLh-84 and HepG2 cells were treated with Phx-3 alone or a combined dose of Phx-3 and 2 DG, depolarization of the mitochondria was extensive, but that of the normal cell line RLN-10 was not. These results may imply that the mechanism for the apoptosis of hepatocellular carcinoma cells caused by Phx-3 alone or a combined dose of Phx 3 and 2-DG differs from that of the normal cell line RLN-10. The present results demonstrate that Phx-3 alone may be beneficial for targeting liver cancer and that its anticancer activity may be enhanced by 2-DG. However, a combined dose of Phx-3 and 2-DG may exert adverse effects on normal liver cells, as evidenced by the cytotoxic and pro-apoptotic effects of the combined treatment in the rat normal hepatocellular cell line RLN-10. PMID- 22076587 TI - Resonant Mie scattering (RMieS) correction applied to FTIR images of biological tissue samples. AB - Recently a resonant Mie scattering (RMieS) correction approach has been developed and demonstrated to be effective for removing the baseline distortions that compromise the raw data in individual spectra. In this paper RMieS correction is extended to FTIR images of a tissue section from biopsy of the human cervical transformation zone and a coronal tissue section of a Wistar rat brain and compared to the uncorrected images. It is shown that applying RMieS correction to FTIR images a) removes baseline distortions from the image spectra and thus reveals previously hidden information on spatial variation of chemical contents within the tissue and b) can lead to improved automatic tissue feature classification through multivariate cluster analysis. PMID- 22076589 TI - Comparison of shear bond strengths of ceramic brackets after different time lags between lasing and debonding. AB - Laser use is effective in the debonding of ceramic brackets. However, a standardization of the laser debonding techniques used has not yet been implemented. The purpose of this study was to evaluate the effect of the time lag elapsed between lasing and shearing on debonding of ceramic brackets. One hundred polycrystalline ceramic brackets were placed on human premolar teeth, which were randomly divided into five groups of 20. One group was assigned as the control. The Er-YAG laser was applied on each bracket in four experimental groups at 5 W for 6 s with the scanning method. Debonding was performed 1 s, 18 s, 30 s, or 60 s after laser exposure. Shear bond strengths and adhesive remnant index scores were measured. Statistically significant difference was observed between the control and experimental groups when the data for the shear bond strengths was considered (p < 0.05). Adhesive remnant index scores of the groups were not statistically different (p > 0.05). Debonding ceramic brackets after 18 s when lased 6 s using an Er-YAG laser with the scanning method is safe and also suitable for clinical use since three brackets can be debonded at a time in succession. PMID- 22076590 TI - Expression of seed dormancy in grain sorghum lines with contrasting pre-harvest sprouting behavior involves differential regulation of gibberellin metabolism genes. AB - Grain sorghum [Sorghum bicolor (L) moench] exhibits intraspecific variability for the rate of dormancy release and pre-harvest sprouting behavior. Two inbred lines with contrasting sprouting response were compared: IS9530 (resistant) and RedlandB2 (susceptible). Precocious dormancy release in RedlandB2 is related to an early loss of embryo sensitivity to ABA and higher levels of gibberellins in imbibed grains as compared with IS9530. With the aim of identifying potential regulatory sites for gibberellin metabolism involved in the expression of dormancy in immature grains of both lines, we carried out a time course analysis of transcript levels of putative gibberellin metabolism genes and hormone content (GA(1), GA(4), GA(8) and GA(34)). A lower embryonic GA(4) level in dormant IS9530 was related to a sharp and transient induction of two SbGA2-oxidase (inactivation) genes. In contrast, these genes were not induced in less dormant RedlandB2, while expression of two SbGA20-oxidase (synthesis) genes increased together with active GA(4) levels before radicle protrusion. Embryonic levels of GA(4) and its catabolite GA(34) correlated negatively. Thus, in addition to the process of gibberellin synthesis, inactivation is also important in regulating GA(4) levels in immature grains. A negative regulation by gibberellins was observed for SbGA20ox2, SbGA2ox1 and SbGA2ox3 and also for SbGID1 encoding a gibberellin receptor. We propose that the coordinated regulation at the transcriptional level of several gibberellin metabolism genes identified in this work affects the balance between gibberellin synthesis and inactivation processes, controlling active GA(4) levels during the expression of dormancy in maturing sorghum grains. PMID- 22076588 TI - Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature. AB - Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6 methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m2 for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered. PMID- 22076591 TI - Urinary exosomal WT1 in childhood nephrotic syndrome. AB - BACKGROUND: Recently, urinary exosomal WT1 has been proposed as a novel biomarker for simple podocyte injury. We investigated urinary exosomal WT1 to confirm its role as a non-invasive biomarker for predicting steroid responsiveness or renal pathological conditions in patients with idiopathic nephrotic syndrome (NS). CASE DIAGNOSIS: Forty children with active NS were recruited. Twenty-eight (70%) were steroid-sensitive, including 3 with minimal change NS (MCNS) and 1 with focal segmental glomerulosclerosis (FSGS). The remaining 12 (30%) were steroid resistant, including 8 with FSGS and 4 with MCNS. Urinary exosomes were isolated by a differential centrifugation method, and WT1 was measured by Western blot analysis. RESULTS: WT1 was detected in 25 patients (62.5%). There was no significant difference in the proportion of the patients with a detectable amount of WT1 according to steroid responsiveness or renal pathological condition, the amount of WT1 showed no significant difference according to steroid responsiveness or renal pathological condition, and there was no significant difference in the amount of proteinuria between patients with or without detectable WT1. CONCLUSIONS: Urinary exosomal WT1 was detected in some patients with NS. However, its role as an appropriate biomarker in childhood NS was not verified in this study. PMID- 22076592 TI - Outcome of children with heavy non-nephrotic proteinuria in Henoch-Schonlein nephritis. PMID- 22076593 TI - Evaluating the "greenness" of chemical processes and products in the pharmaceutical industry--a green metrics primer. AB - This tutorial review presents an overview of the main metrics that have been used to test and compare the 'greenness' of processes and products, primarily in the pharmaceutical industry. The green metrics cover areas of resources, materials, processing, cleaning, life cycle assessment, renewability, amongst others. Application examples of these metrics are also presented to illustrate key points and concepts. PMID- 22076594 TI - Relapse to smoking and postpartum weight retention among women who quit smoking during pregnancy. AB - Postpartum weight retention contributes to obesity risk in women. Given that most women who quit smoking as a result of pregnancy will resume smoking within 6 months postpartum and that there is a robust association between smoking and weight, we sought to evaluate postpartum weight retention as a function of postpartum smoking status among women who had quit smoking during pregnancy. Women (N = 183) with biochemically confirmed cigarette abstinence at the end of pregnancy were recruited between February 2003 and November 2006. Women self reported demographic information and weight before pregnancy. Smoking status and weight were documented at the end of pregnancy and at 6, 12, and 24 weeks postpartum. Breastfeeding was reported at 6 weeks postpartum. Differences in weight retention by relapse status at each assessment were evaluated. To examine weight retention in the presence of conceptually relevant covariates, mixed models with log-transformed weight data were used. At 24 weeks postpartum, 34.6% of women remained abstinent. Women who remained abstinent throughout the 24-week period retained 4.7 +/- 2.1 kg more than did women who had relapsed by 6 weeks postpartum, P = 0.03. This difference in postpartum weight retention was significant after controlling for relevant covariates (age, race, breastfeeding, and pregravid BMI). Resumption of smoking within the first 6 weeks following childbirth is associated with decreased postpartum weight retention, even after controlling for breastfeeding and pregravid weight. Interventions to sustain smoking abstinence postpartum might be enhanced by components designed to minimize weight retention. PMID- 22076595 TI - Randomized controlled trial of chewing gum for weight loss. AB - The possible effects on body weight of chewing gum on a regular schedule have not been tested in a randomized controlled trial (RCT). We conducted an 8-week RCT in 201 overweight and obese adults to test the hypothesis that receiving printed material on good nutrition and chewing gum for a minimum of 90 min/day (n = 102) would lead to greater weight loss than receiving printed nutrition information only (n = 99). Changes in BMI, waist circumference, and blood pressure were secondary outcomes. Adherence to the gum-chewing protocol in the intervention group was >95%. In the intention-to-treat analysis, there were virtually no changes in weight or BMI in either group between baseline and the end of the intervention at 8 weeks. Waist circumference decreased significantly in the intervention group between baseline and 8 weeks (mean +/- SD change = -1.4 +/- 5.3 cm; P = 0.0128); however, there was no significant difference in change in waist circumference comparing the groups. Similarly, systolic and diastolic blood pressure decreased significantly in the intervention group between baseline and 8 weeks (-3.0 +/- 9.9 mm Hg; P = 0.0032 and -3.2 +/- 7.3 mm Hg; P = 0.0001, respectively); however, there were no significant differences in the changes in systolic or diastolic blood pressure between the groups. Analyses including completers only produced essentially the same results. We conclude that chewing gum on a regular schedule for 8 weeks did not facilitate weight loss in these overweight and obese adults. PMID- 22076596 TI - Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study. AB - The objective of this pilot study was to evaluate the effects of exenatide on BMI (primary endpoint) and cardiometabolic risk factors in nondiabetic youth with extreme obesity. Twelve children and adolescents (age 9-16 years old) with extreme obesity (BMI >=1.2 times the 95th percentile or BMI >=35 kg/m(2)) were enrolled in a 6-month, randomized, open-label, crossover, clinical trial consisting of two, 3-month phases: (i) a control phase of lifestyle modification and (ii) a drug phase of lifestyle modification plus exenatide. Participants were equally randomized to phase-order (i.e., starting with control or drug therapy) then crossed-over to the other treatment. BMI, body fat percentage, blood pressure, lipids, oral glucose tolerance tests (OGTT), adipokines, plasma biomarkers of endothelial activation, and endothelial function were assessed at baseline, 3-, and 6-months. The mean change over each 3-month phase was compared between treatments. Compared to control, exenatide significantly reduced BMI ( 1.7 kg/m(2), 95% confidence interval (CI) (-3.0, -0.4), P = 0.01), body weight ( 3.9 kg, 95% CI (-7.11, -0.69), P = 0.02), and fasting insulin (-7.5 mU/l, 95% CI (-13.71, -1.37), P = 0.02). Significant improvements were observed for OGTT derived insulin sensitivity (P = 0.02) and beta-cell function (P = 0.03). Compliance with the injection regimen was excellent (>=94%) and exenatide was generally well-tolerated (the most common adverse event was mild nausea in 36%). These preliminary data suggest that exenatide should be evaluated in larger, well controlled trials for its ability to reduce BMI and improve cardiometabolic risk factors in youth with extreme obesity. PMID- 22076598 TI - Enhancement of static incubation time in microfluidic cell culture platforms exploiting extended air-liquid interface. AB - Microfluidics based cell culture applications have facilitated the study of cellular dynamics at the single entity level. Yet, long term versions of such applications in a static framework suffer from the fast exhaustion of available oxygen, dissolved in the limited media volume available per cell, within the microconfined environment. In order to circumvent such drawbacks, we have improvised a microfluidic cell culture platform for prolonged sustenance of adherent mammalian cells by formation of an air-liquid interface through functionalizing inner surfaces of a polydimethylsiloxane (PDMS) based microdevice. We have demonstrated an augmented static incubation time for different cell lines using this approach. PMID- 22076597 TI - Immunological characteristics and two novel mutations in TACI in a cohort of 28 pediatric patients with common variable immunodeficiency. AB - Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production. Mutations in the gene encoding TACI (TNFRSF13B) were previously found to be associated with CVID. Previous studies have identified a variety of sequence variants in TACI where A181E and C104R were the most common, with variable frequencies in different ethnic populations. So far, no mutations were identified in the recently reported "TACI highly conserved" (THC) cytoplasmic domain, important for the induction of class switch recombination. Our study evaluated immunological and clinical data on a cohort of 28 Argentinean pediatric CVID patients and allowed the identification of two novel mutations in TNFRSF13B, including one, S231R, affecting the highly conserved THC domain. In contrast, none of the patients presented with A181E and C104R mutations. PMID- 22076599 TI - The metabolic syndrome of fructose-fed rats: effects of long-chain polyunsaturated omega3 and omega6 fatty acids. IV. D-glucose metabolism by isolated pancreatic islets. AB - The major aim of the present study was to search for changes of D-glucose metabolism in isolated pancreatic islets possibly involved in the alteration of their secretory response to the hexose, as observed when comparing rats exposed for 8 weeks to diets containing either starch and sunflower oil or fructose and sunflower oil, as well as rats exposed to diets containing fructose, sunflower oil and either salmon oil or safflower oil. The substitution of starch by fructose in the diet affected unfavourably D-glucose phosphorylation by the isolated islets. In the fructose-fed rats, there was a close parallelism between D-[5-3H]glucose utilization and the dietary omega3/omega6 fatty acid ratio. There was little to distinguish, however, between the four groups of rats in terms of D [U-14C]glucose oxidation. The paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization, which always increased as the concentration of the hexose was raised from 2.8 to 8.3 and 16.7 mM, was tightly related, in the fructose-fed rats, to the HOMA index for insulin resistance. PMID- 22076600 TI - Giving the wrong impression: food and beverage brand impressions delivered to youth through popular movies. AB - BACKGROUND: Marketing on television showcases less-healthful options, with emerging research suggesting movies promote similar products. Given the obesity epidemic, understanding advertising to youth should be a public health imperative. The objective of this study was to estimate youth impressions to food and beverages delivered through movies. METHODS: Impressions were calculated by dividing US receipts annually into average movie ticket prices, then multiplying this by the number of brand appearances. Examination by ratings, product types and ages were conducted by Spearman rank correlation coefficient tests. RESULTS: Youth in the USA saw over 3 billion food, beverage or food-retail establishment (FRE) impressions on average, annually from 1996 to 2005. Those aged 12-18 viewed over half of all impressions, with PG-13-rated movies containing 61.5% of impressions. There were no significant trends in brand appearances by food, beverage or FRE impressions over the decade, although there was a decreasing trend in R-rated impressions for both foods (P< 0.01) and beverages (P< 0.01), but not FREs (P= 0.08). CONCLUSIONS: Movies promote billions of food and beverage impressions annually to youth. Given the public health crisis of obesity, future research should further investigate these trends, as well as the potential association of these unhealthy exposures in youth. PMID- 22076601 TI - Lipid, lipoproteins, total antioxidant status and organ changes in rats administered high doses of cadmium chloride. AB - OBJECTIVE: To determine the possible association between cadmium (Cd) exposure and alterations in plasma lipid and lipoprotein levels and total antioxidant status (TAS) in rats. MATERIALS AND METHOD: Twenty male albino rats assigned to 2 groups of 10 rats each (test and control) were used for the study. Each test animal model was given 1.0 mg CdCl(2)/kg body weight, administered intraperitoneally for 4 weeks. Blood samples obtained from both groups at the beginning (baseline) and after 4 weeks of Cd exposure were analysed for triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), TAS and Cd. Kidney and liver sections from the rats were examined. RESULTS: The plasma TG, TC and LDLC levels were significantly higher in exposed rats than controls (p < 0.0001, p < 0.0001 and p < 0.001, respectively). Plasma HDLC was reduced in the exposed rats compared to controls (0.41 +/- 0.22 and 0.68 +/- 0.14 mmol/l, respectively). CONCLUSION: The observed dyslipidaemia and decrease in TAS could be due to increased free radical production causing oxidative stress. Damage to liver and kidney sections in the exposed group suggests that Cd toxicity results in detrimental histological changes and may be implicated in the aetiology of cerebrovascular diseases. PMID- 22076602 TI - Is there still any role for minilaparoscopic-cholecystectomy? A general surgeons' last five years experience over 932 cases. AB - Laparoscopy has rapidly emerged as the preferred surgical approach in a number of different diseases because it ensures correct diagnoses and appropriate treatment. The use of mini-instruments (5 mm or less in diameter) and, when possible, the reduction of the number of trocars used might be its natural evolution. Laparoscopic cholecystectomy is a gold standard technique. The aim of the present work is to illustrate the results of the prospective experience of minilaparoscopic cholecystectomy (5 mm MLC) performed at our institution. Between August 2005 and July 2010 a total of 932 patients (mean age 45 years) underwent a laparoscopic cholecystectomy. Amongst them, 887 (95.1%) were operated on with a 5 mm-three trocar approach and in the remaining 45 cases (4.8%) a 3 mm trocar was used. The primary endpoint was the feasibility rate of the techniques. Secondary endpoints were safety and the impact of the techniques on duration of laparoscopy. In two cases conversion to laparotomy was necessary. We needed to add a fourth-5 mm trocar in the 10.7% of the cases (95 patients) in the 5 mm MLC. There were two cases of redo-laparoscopy in this group due to bile leakage from the cystic duct in one case, and to bleeding from the gallbladder bed in the other. Minor occurrence ranged as high as 2.1% in the 5 mm-MLC group, while it was nil in the 3 mm-MLC patients. The present experience shows that the 5 mm three trocars MLC is a safe, easy, effective and reproducible approach to gallbladder diseases. Such features make the technique a challenging alternative to conventional laparoscopy both in the acute and the scheduled setting. We consider the 3 mm-MLC approach suitable only in selected cases, young and thin patients, due to the fragility of the smaller instruments. PMID- 22076604 TI - Evidence for a general factor model of ADHD in adults. AB - OBJECTIVE: To examine factor structures of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) symptoms of ADHD in adults. METHOD: Two sets of models were tested: (a) models with inattention and hyperactivity/impulsivity as separate but correlated latent constructs and (b) hierarchical general factor models with a general factor for all symptoms and separate specific factors for inattention and hyperactivity/impulsivity. Participants were 751 adults with ADHD. Two models with correlated factors and two general factor models of ADHD symptoms were tested. RESULTS: The general factor model provided a better fit of the data than the correlated models. The general factor model with one general and three (inattention, motoric, and verbal hyperactivity/impulsivity) specific factors best accounted for the adults' symptoms. CONCLUSION: These results suggest a unitary component to ADHD symptoms as well as dimensional specific factors. The replication of a general factor in adults suggests continuity of symptom presentation from childhood into adulthood. Clinical implications are discussed. PMID- 22076605 TI - Methylation profiling in non-small cell lung cancer: clinical implications. AB - The aim of this study was to identify a panel of methylation markers that distinguish non-small cell lung cancers (NSCLCs) from normal lung tissues. We also studied the relation of the methylation profile to clinicopathological factors in NSCLC. We collected a series of 46 NSCLC samples and their corresponding control tissues and analyzed them to determine gene methylation status using the Illumina GoldenGate Methylation bead array, which screens up to 1505 CpG sites from 803 different genes. We found that 120 CpG sites, corresponding to 88 genes were hypermethylated in tumor samples and only 17 CpG sites (16 genes) were hypomethylated when compared with controls. Clustering analysis of these 104 genes discriminates almost perfectly between tumors and normal samples. Global hypermethylation was significantly associated with a worse prognosis in stage IIIA NSCLC patients (P=0.012). Moreover, hypermethylation of the CALCA and MMP-2 genes were statistically associated to a poor clinical evolution of patients, independently of TNM tumor stage (P=0.06, RR=2.64; P=0.04, RR=2.96, respectively). However, hypermethylation of RASSF1 turned out to be a protective variable (P=0.02; RR=0.53). In conclusion, our results could be useful for establishing a gene methylation pattern for the detection and prognosis of NSCLC. PMID- 22076607 TI - shRNA against CD44 inhibits cell proliferation, invasion and migration, and promotes apoptosis of colon carcinoma cells. AB - CD44 is a causal factor for tumor invasion, metastasis and acquisition of resistance to apoptosis. CD44 knockdown using inducible short hairpin RNA (shRNA) significantly reduces cell growth and invasion. Short hairpin RNA against CD44 and pGFP-V-RS-vector was used for knockdown of CD44 expression in SW620 colon cancer cells. Cell growth, invasion and migration assay, immunofluorescence for beta-catenin expression and western blotting for Wnt signaling molecules were analyzed. Cell cycle analysis and western blot analysis for apoptotic molecules were evaluated. Short hairpin RNA against CD44 reduced the expression of CD44. Cell proliferation, migration and invasion were markedly inhibited and apoptosis was increased in shRNA CD44-transfected cells. Knockdown of CD44 decreased the phosphorylation of PDK1, Akt and GSK3beta, and beta-catenin levels. Decreased phosphorylated Akt led to an increase in phosphorylated FoxO1 and induced cell cycle arrest in the G0-G1 phase and a decrease in the S phase. The levels of Bcl 2 and Bcl-xL expression were down-regulated, while the levels of BAX expression and cleaved caspase-3, -8 and -9 were increased. CD44 knockdown by way of shRNA inhibited cell proliferation and induced cell apoptosis. This can be used as a therapeutic intervention with the anti-survival/pro-apoptotic machinery in human colon cancer. PMID- 22076608 TI - DNA methylation patterns of Brachypodium distachyon chromosomes and their alteration by 5-azacytidine treatment. AB - Sequential immunolocalisation of 5-methylcytosine (5-MeC) and fluorescence in situ hybridisation with chromosome-specific BAC clones were performed on Brachypodium distachyon mitotic metaphase chromosomes to determine specific DNA methylation patterns of each chromosome in the complement. In the majority of cells examined, chromosomes Bd4 and Bd5, which bear the loci of 5S and 35S ribosomal DNA, respectively, had characteristic 5-MeC patterns. In contrast, the distribution of 5-MeC along the metacentric chromosome pairs Bd1, Bd2 and Bd3 was more variable. There were numerous differences in distribution of methylated sites between homologous chromosomes as well as between chromosome arms. Some chromosome sites, such as pericentromeric regions, were highly methylated in all chromosomes. Additionally, the influence of a hypomethylating agent, 5 azacytidine, on B. distachyon chromosome methylation patterns was confirmed. It was found that some chromosome pairs underwent demethylation more easily than others, but there was no apparent regularity in demethylation of particular chromosome segments. PMID- 22076609 TI - Feasibility of enhanced recovery programme in various patient groups. AB - INTRODUCTION: An accelerated multi-modal rehabilitation programme may improve the recuperation and reduce the complication rate in patients undergoing colorectal surgery. The aim of this study was to see whether fast-track recovery is feasible in various patient groups. PATIENTS AND METHODS: Data on all patients operated for intestinal pathology from July 2006-April 2008 were prospectively collected for this prospective study. All included patients entered a multi-modal rehabilitation programme. Peri- and postoperative complications and readmissions, pathology reports and operation characteristics were recorded prospectively. RESULTS: Three hundred and forty-eight patients underwent colorectal surgery. No difference in readmission rate was found between various patient groups. The only significant differences after multivariate regression analysis were in re operation rate and length of stay in favour of the elective surgery group. CONCLUSIONS: Fast-track modalities can be introduced with a low complication rate in all patient groups. Length of stay in elderly patients averages 10 days, implying that this group cannot be considered as "fast track", although the same protocol can also be applied in this group. Better organization of the aftercare might however considerably change the length of stay of elderly patients, since postoperative complications do not differ between old and young patients. PMID- 22076606 TI - Serotonin and prefrontal cortex function: neurons, networks, and circuits. AB - Higher-order executive tasks such as learning, working memory, and behavioral flexibility depend on the prefrontal cortex (PFC), the brain region most elaborated in primates. The prominent innervation by serotonin neurons and the dense expression of serotonergic receptors in the PFC suggest that serotonin is a major modulator of its function. The most abundant serotonin receptors in the PFC, 5-HT1A, 5-HT2A and 5-HT3A receptors, are selectively expressed in distinct populations of pyramidal neurons and inhibitory interneurons, and play a critical role in modulating cortical activity and neural oscillations (brain waves). Serotonergic signaling is altered in many psychiatric disorders such as schizophrenia and depression, where parallel changes in receptor expression and brain waves have been observed. Furthermore, many psychiatric drug treatments target serotonergic receptors in the PFC. Thus, understanding the role of serotonergic neurotransmission in PFC function is of major clinical importance. Here, we review recent findings concerning the powerful influences of serotonin on single neurons, neural networks, and cortical circuits in the PFC of the rat, where the effects of serotonin have been most thoroughly studied. PMID- 22076610 TI - Clinicopathologic features and prognostic analysis of MSI-high colon cancer. AB - PURPOSE: The objectives of the study were to estimate the incidence and clarify the clinicopathologic feature of sporadic microsatellite instability (MSI)-high (MSI-H) colon cancer. Furthermore, the role of MSI in colon cancer prognosis was also investigated. METHODS: Microsatellite status was identified by genotyping. The clinicopathologic differences between two groups (MSI-H vs. MSI-L/S) and the prognostic value of MSI were analyzed. RESULTS: From 1993 to 2006, 709 sporadic colon cancer patients were enrolled. MSI-H colon cancers showed significant association with poorly differentiated (28.3% vs. 7.2%, p = 0.001), proximally located (76.7% vs. 34.5%, p = 0.001), more high mucin-containing tumor (10.0% vs. 5.1%, p = 0.001) and female predominance (56.7% vs. 30.2%, p = 0.001). In multivariate analysis, MSI-H is an independent factor for better overall survival (HR, 0.459; 95% CI, 0.241-0.872, p = 0.017). CONCLUSIONS: Based on the hospital based study, MSI-H colon cancers demonstrated distinguished clinicopathologic features from MSI-L/S colon cancers. MSI-H is an independent favorable prognostic factor for overall survival in colon cancer. PMID- 22076611 TI - DNA topoisomerase II alpha: a favorable prognostic factor in colorectal caner. AB - PURPOSE: There is a lack of study concerning expression of Topoisomerase IIalpha (Topo IIalpha) and long-term results in colorectal cancer patients. We aimed to investigate the relationship between expression of Topo IIalpha and clinicopathological parameters including overall survival in colorectal cancer. METHODS: Paraffin-fixed specimens from a large prospective cohort of colorectal cancer patients who had been followed up for 4 years were assayed immunohistochemically. RESULTS: Of 490 colorectal cancer patients accessible for Topo IIalpha expression, expression of Topo IIalpha was scored as (-) in 4 (0.8%) patients, (+) in 41 (8.4%) patients, (++) in 396 (80.8%) patients, and (+++) in 49 (10.0%) patients. Overexpression of Topo IIalpha was found to be related with lower T stage (p = 0.042), lower N stage (p = 0.038), and a lower incidence of recurrence with nearly significance (p = 0.053). Kaplan-Meier analyses showed that overexpression of Topo IIalpha was related with prolonged overall survival (p = 0.022) and disease-free survival (p = 0.036). Multivariate analyses showed that elevated serum CEA (p < 0.001), elevated serum CA199 (p = 0.002), poor differentiation (p = 0.001), advanced Dukes stage (p < 0.001), and lower expression of Topo IIalpha (p = 0.017) were independent predictive factors for poor prognosis. CONCLUSIONS: Topo IIalpha expression is a valuable prognostic indicator for colorectal cancer and would be useful in treatment selection for early colorectal cancer and malignant colorectal polyps resected under endoscopy, especially when it is used in combination with serum CEA, CA199, and differentiation. PMID- 22076612 TI - Meta-analysis of the association between progression-free survival and overall survival in metastatic colorectal cancer. AB - PURPOSE: The validity of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic colorectal cancer (mCRC) trials has been studied, primarily in first-line treatment. The relationship between PFS and OS has not been well studied in later lines of treatment. METHODS: We conducted a systematic literature review of mCRC phase 2 and 3 clinical trials that reported OS and PFS (or time-to-progression [TTP]) data. Correlation between endpoints (either PFS alone or PFS aggregated with TTP [PFS_TTP]) was estimated within treatment arms. Treatment effect was the ratio of the median time to OS, PFS, or PFS_TTP in the "control" versus "experimental" arm. We conducted meta-regression analyses and performed receiver-operating characteristic (ROC) analysis. RESULTS: We analyzed data from 62 articles (23,527 patients). A high positive correlation was found between median PFS_TTP and median OS within treatment arms (r = 0.87; 95% confidence interval [CI], 0.82-0.91) and also between the median OS and median PFS (r = 0.89, 95% CI, 0.83-0.93)]. R(2) was 0.48 for PFS_TTP and 0.59 for PFS; R (2) for PFS_TTP was higher for first-line (R(2) = 0.54) than second-line studies (R(2) = 0.38). The ROC analysis is presented as a conceptual tool for evaluating the performance of PFS as a surrogate for OS at various thresholds. CONCLUSIONS: The correlation of PFS, alone or aggregated with TTP, with OS in clinical trials of patients with mCRC is robust across lines of therapy and provides a useful means of predicting improvements in OS using PFS data. PMID- 22076613 TI - Tissue factor/activated factor VIIa induces matrix metalloproteinase-7 expression through activation of c-Fos via ERK1/2 and p38 MAPK signaling pathways in human colon cancer cell. AB - PURPOSE: Increased expression of tissue factor (TF) is associated with tumor invasion and metastasis in human colorectal cancer. We have previously observed that TF/FVIIa upregulates matrix metalloproteinase-7 (MMP-7) expression at the transcriptional level in colon cancer cells. MMP-7 overexpression is believed to play an important role in tumor invasion and metastasis. The aim of this study is to elucidate the molecular mechanisms by which TF/FVIIa induced MMP-7 expression and cell invasion in vitro. METHODS: Reverse transcription polymerase chain reaction, Western blot, luciferase assay, and chromatin immunoprecipitation (ChIP) were used to determine the potential mechanism and signaling pathways by which TF/FVIIa induced MMP-7 expression and cell invasion in LoVo cells. Small interfering RNA (siRNA) and cell invasion assay was used to examine whether blocking c-Fos expression could abolish FVIIa-mediated upregulation of MMP-7 and cell invasion in vitro. RESULTS: The results showed that FVIIa induced the upregulation of MMP-7 both at the mRNA and protein levels in a time- and dose dependent manner and increased the invasive behavior of LoVo cells. FVIIa enhanced the promoter activity of MMP-7, and the activator protein-1 (AP-1) binding site was responsible for the activation. Site mutation of the AP-1 binding site in the promoter almost completely abolished FVIIa-mediated response. Furthermore, ChIP assay confirmed that FVIIa promoted the direct binding of c-Fos with the MMP-7 promoter in vivo. FVIIa also induced the expression and nuclear accumulation of the AP-1 subunit c-Fos. siRNA-mediated knockdown of c-Fos eliminated FVIIa-stimulated MMP-7 expression and cell migration in vitro. In addition, selective mitogen-activated protein kinase (MAPK) kinase (MEK1/2) inhibitor (PD98059) and p38 MAPK inhibitor SB203580 suppressed MMP-7 upregulation induced by FVIIa. CONCLUSIONS: Our data suggest that a novel TF/FVIIa/MAPK/c Fos/MMP-7 axis plays an important role in modulating the invasion of colon cancer cells and blockage of this pathway holds promise to treat colon cancer metastasis. PMID- 22076614 TI - Developing luminescent silver nanodots for biological applications. AB - Though creation and characterization of water soluble luminescent silver nanodots were achieved only in the past decade, a large variety of emitters in diverse scaffolds have been reported. Photophysical properties approach those of semiconductor quantum dots, but relatively small sizes are retained. Because of these properties, silver nanodots are finding ever-expanding roles as probes and biolabels. In this critical review we revisit the studies on silver nanodots in inert environments and in aqueous solutions. The recent advances detailing their chemical and physical properties of silver nanodots are highlighted with an effort to decipher the relations between their chemical/photophysical properties and their structures. The primary results about their biological applications are discussed here as well, especially relating to their chemical and photophysical behaviours in biological environments (216 references). PMID- 22076616 TI - Using the inflating syringe as a safety valve to limit laryngeal mask airway cuff pressure. AB - OBJECTIVE: Hyperinflation of the laryngeal mask airway (LMA) cuff is thought to be the etiology underlying many of the complications associated with the use of this device. Until now, there has not been a clinically acceptable method (besides direct measurement) to assure that the cuff pressure is maintained less than the recommended maximum value of 44 mm Hg (60 cm H(2)O). METHODS: We inflated sizes #2 and #5 LMAs with air to 40, 60, or 120 mm Hg starting pressures, using 30- and 60-ml BDTM and B BraunTM syringes; we then allowed the syringe plungers to recoil to equilibrium before removing the syringe from the LMA inflation port. Residual LMA cuff pressures following complete passive recoil were measured and recorded. RESULTS: A number of combinations of syringes (30 and 60 ml) and starting pressures (40, 60, 120 mm Hg) resulted in safe residual (#2 and #5 LMA) cuff pressures of <44 mm Hg. CONCLUSION: When using specific combinations of syringes, LMA sizes and inflation pressures, these data demonstrate an efficient, practical and easy method to achieve an initial equilibrium recoil LMA cuff pressure that is less than, or very near to, the recommended upper safe limit of 44 mm Hg. PMID- 22076615 TI - Comparison of SNAPTM II and BIS Vista indices during normothermic cardiopulmonary bypass under isoflurane anesthesia. AB - OBJECTIVE: Processed EEG monitoring during cardiopulmonary bypass (CPB) may help determine loss of consciousness and depth of anesthesia. This study compared the SNAP(TM) II and BIS Vista monitors in patients undergoing isoflurane anesthesia with normothermic CPB. METHODS: 40 subjects undergoing CPB with isoflurane anesthesia were enrolled. Subjects were premedicated with 1-2 mg midazolam approximately 5 min prior to acquisition of baseline index values and anesthesia induced with midazolam and fentanyl. Anesthesia was maintained with isoflurane, midazolam, and fentanyl and a cis-atracurium infusion. SNAP(TM) II (version 1.2.9 algorithm 1.88) and BIS Vista (application version 3.00 platform version 2.03) indices were recorded at baseline, pre-induction, post-intubation, incision, start of CPB, every 15 min during CPB, end of CPB, and end of case. Agreement between methods was determined using Pearson correlation and the Bland-Altman method with repeated observa- tions. RESULTS: Twenty-four male and 12 female subjects completed the analysis. The correlation between SNAP(TM) II and BIS Vista index values was 0.61 (P < 0.005). A linear relationship between the difference in the indices and the average index values was observed following the induction of anesthesia. In awake subjects, the bias between the SNAP(TM) II and BIS Vista was 5 (95% CI 3-7). The limits of agreement were 23 (95% CI 19-26) and 13 (95% CI -9--16). During anesthesia, the mean difference on a log scale was 0.11 (95% CI 0.09-0.12). The limits of agreement were 0.43 (95% CI 0.40-0.45) and -0.21 (95% CI -0.18--0.24). The antilog of the mean difference demonstrated that the SNAP(TM) II value was 28% (95% CI 24-33%) higher than the BIS Vista value following induction of anesthesia. CONCLUSIONS: The SNAP(TM) II monitor demonstrates a consistently positive bias during cardiopulmonary bypass under isoflurane anesthesia compared with the BIS Vista. PMID- 22076617 TI - Optimality and thermodynamics determine the evolution of transcriptional regulatory networks. AB - Transcriptional motifs are small regulatory interaction patterns that regulate biological functions in highly-interacting cellular networks. Recently, attempts have been made to explain the significance of transcriptional motifs through dynamic function. However, fundamental questions remain unanswered. Why are certain transcriptional motifs with similar dynamic function abundant while others occur rarely? What are the criteria for topological generalization of these motifs into complex networks? Here, we present a novel paradigm that combines non-equilibrium thermodynamics with multiobjective-optimality for network analysis. We found that energetic cost, defined herein as specific dissipation energy, is minimal at the optimal environmental conditions and it correlates inversely with the abundance of the network motifs obtained experimentally for E. coli and S. cerevisiae. This yields evidence that dissipative energetics is the underlying criteria used during evolution for motif selection and that biological systems during transcription tend towards evolutionary selection of subgraphs which produces minimum specific heat dissipation under optimal conditions, thereby explaining the abundance/rare occurrence of some motifs. We show that although certain motifs had similar dynamical functionality, they had significantly different energetic cost, thus explaining the abundance/rare occurrence of these motifs. The presented insights may establish global thermodynamic analysis as a backbone in designing and understanding complex networks systems, such as metabolic and protein interaction networks. PMID- 22076618 TI - Clobetasol down-regulates SLPI expression in U937 monocytoid cells. AB - In order to investigate how glucocorticoids affect the expression of secretory leukocyte peptidase inhibitor (SLPI), which is overexpressed in a variety of cancers, clobetasol was added to cell culture medium of U937 cells and the SLPI mRNA levels were examined. The in vitro effect of the treatment on SLPI expression was detected by reverse transcriptase-polymerase chain reaction. Clobetasol treatment of U937 cells induced an up- and down-regulation of SLPI expression in a dose-dependent manner. Western blotting confirmed the down regulation of SLPI protein expression. We hypothesized a loop formation in the SLPI genome domain, in which the glucocorticoid receptor regulates bi-directional transcriptional activity. PMID- 22076619 TI - In response to "Clinical features and management of carboplatin-related hypersensitivity reactions in pediatric low grade glioma". PMID- 22076620 TI - Cancer as biographical disruption: constructions of living with cancer. AB - PURPOSE: From a cancer survivor perspective, the purpose of this paper is to explore what has changed in their lives that they attribute to the disease. The rationale for the study is that evidence of the extent to which cancer disrupts people's lives in the longer term is contradictory. METHODS: Written accounts from 40 cancer survivors were analysed using interpretative methods. The researchers drew on the concept of biographical disruption as a framework for analysis. RESULTS: Cancer survivors construct cancer as a biographically disruptive event with ongoing physical and psychosocial impacts. Cancer is constructed as a permanent threat to life which is responsible for increasing their awareness of their own mortality and invoking positive changes to self. These formulations of living with cancer were found across a range of participants, including those who defined themselves as currently free of cancer, those who had recurrence, those who had been diagnosed 5 years ago and those who had been free of cancer for a long time. CONCLUSIONS: This study adds to the body of literature exploring how to enhance supportive care for cancer survivors by reflecting on biographical disruption and continuity, and the complexities within individual constructions of changes in life that they attribute to cancer. Cancer survivors should be given opportunities to articulate the impact of cancer, thus giving legitimate space to talk about cancer's ongoing resonance on life so that problems and difficulties are not dismissed or trivialised. PMID- 22076621 TI - Bridging the distance: a prospective tele-oncology study in Northern Norway. AB - PURPOSE: The University Hospital of North Norway (UNN) is a tertiary-level hospital and has the main responsibility of providing specialized cancer health care in the remote area of Northern Norway. Weekly videoconferences (VCs) have been established to enable clinicians at a local hospital and primary cancer health care providers in five different communities to discuss cases with specialist cancer care services at UNN. In this study, we aimed to evaluate the feasibility of these VCs. METHODS: This is a prospective registration study. Descriptive data were collected at UNN, and for each patient discussed at the VC, a survey was completed by the local health care provider responsible for the patient. RESULTS: During an 18-month period, 167 cases were discussed (101 patients). A median of 7 health care providers participated in each VC. According to the local physicians and nurses, the VCs contributed in 96% of cases to give "quite a bit" or "very much" confidence in adequate patient care. They reported that patient care in 85% of cases would be improved "quite a bit" or "very much" due to the VC. The mean number of days waiting for VC were 2.0 days (range, 0-7; SD, 2.0) and was significantly shorter (P < 0.001) than the estimated time waiting if alternative consultations were to be used (mean, 10.2 days (range, 0 30; SD, 5.8)). CONCLUSION: VC may be a useful supplemental tool to support primary health care providers at local hospitals and remote communities in their effort to offer efficient and high-quality cancer care. PMID- 22076622 TI - Identification and phylogenetic characterization of a new subfamily of alpha amylase enzymes from marine microorganisms. AB - A gene encoding a starch-hydrolyzing enzyme was isolated from a marine metagenomic library and overexpressed in Escherichia coli. The enzyme, designated AmyP, shows very low similarity to full-length sequences of known alpha-amylases, although a catalytic domain correlated with the alpha-amylase superfamily was identified. Based on the range of substrate hydrolysis and the product profile, the protein was clearly defined as a saccharifying-type alpha-amylase. Sequence comparison indicated that AmyP was related to four putative glycosidases previously identified only in bacterial genome sequences. They were all from marine bacteria and formed a new subfamily of glycoside hydrolase GH13. Moreover, this subfamily was closely related to the probable genuine bacterial alpha amylases (GH13_19). The results suggested that the subfamily may be an independent clade of ancestral marine bacterial alpha-amylases. PMID- 22076623 TI - [Anniversaries: Assistenza Infermieristica e Ricerca, but not only]. AB - The 30th anniversary of Assistenza Infermieristica e Ricerca is the occasion for a reflection on the past and future of a journal whose aim is to publish but, above all, to promote research in/on nursing care, stimulating confrontations, trying to describe and to find answers to unmet needs. PMID- 22076624 TI - [A prospective study on the effectiveness of a project for early discharge of elderly and frail patients from the emergency department]. AB - OBJECTIVE: Frail patients have increased chances of access to Emergency Department (ED) and hospital admission. ED discharge of frail patients (FP) implies high risk of poor outcome. A program of early ED discharge of FPs managed by community nurses (CN) for patients whose hospitalization is not indicated, but cannot be discharged is described. METHODS: Prospective observational study. A CN, in cooperation with other professionals, assessed the feasibility of discharge and activated the appropriate facilities for a safe patient return to the community. Patients' length of stay in ED, mortality and readmission rate to ED 3 months after discharge were measured. RESULTS: The mean age of the 210 enrolled patients was 82.9 years. The reasons for ED access were either acute or worsened chronic diseases, mainly related to orthopedic/traumatic events and pain. Ninety-two persons were sent back home and 118 to residential facilities. In the following 3 months, mortality was 15.7%; almost 36% of discharged patients had at least one access to hospital and the overall readmission rate was 55.7%, higher in sent home group. DISCUSSION: CNs, when integrated with other ED staff, can successfully manage early discharges of 'at risk' patients. The high readmission rate may reflect some enduring difficulties to manage in the community, problems traditionally treated in hospital. PMID- 22076625 TI - [Intention to leave the hospital among nurses with <= 3 years of work experience: an exploratory study]. AB - INTRODUCTION: The retention of nursing workforce is one of the challenges of nursing managers. Since the turnover intention is associated to the real turnover, a deeper understanding of reasons why young nurses would leave the hospital could give some hints to help to retain them. AIM: To explore the factors that affect the turnover intention in nurses with a work experience <3 years. METHODS: Nurses with <3 years of experience, working in 3 large Italian hospitals completed a questionnaire aimed at exploring the turnover intention, job satisfaction, perception of self-competence, organizational commitment, perception of organizational support and of the quality of delivered care, asking to express their agreement on a likert scale from 1 to 5. RESULTS: The results showed that 34.4% of the nurses intended to leave the hospital within 1 year, 43.8% of them had already asked to be transferred a to another hospital. The majority of nurses who intended to leave were male, with a full time employment and living farther than 30 kilometers from the hospital. Moreover they were less satisfied with their current job, for the relationship with the colleagues, the Nurse Manager and the physicians, perceived themselves less competent, less committed to their unit and less supported by the organization compared with than nurses who intended to stay. CONCLUSIONS: This study supports the importance of increasing job satisfaction and organizational commitment for nurses'retention. PMID- 22076626 TI - [The validation of C-POT (Critical-Care Pain Observation Tool) scale: a tool for assessing pain in intensive care patients]. AB - Pain in intensive care units is a frequent and often undermanaged problem, mainly because appropriate pain assessment tools for non communicative patients are still missing. The Critical-Care Pain Observation Tool (C-POT) is currently considered one of the best scales, both for psychometric properties and clinical feasibility. AIM: To preliminarily analyze the reliability and validity of the C POT in a hospital setting, and its clinical feasibility. METHODS: 50 nursing staff members from three different critical care settings of Vicenza Hospital administered the C-POT to 121 in patients, at rest and after usual nursing care activities. In addition, NOPPAIN forms were completed during care activities and communicative patients were asked to rate their pain using numerical rating scale 0-10. Reliability, with Cronbach's alfa and inter-rater agreement (Spearman's non parametric rank correlation), as well as criterion, concurrent and discriminant validity were determined. RESULTS: A good internal consistency and good levels of agreement between independent raters were observed (rhoSpearman 0.55 at rest and 0.66 during activity). Moderate correlations between C-POT and numerical rating scale 0-10, and between C-POT and NOPPAIN were found. Moreover, C-POT scores varied from rest to activities, and from non painful to painful procedures. DISCUSSION: C-POT showed good psychometric properties in terms of reliability and validity; these results, added to positive nurses evaluations, support its utility and use in the clinical setting. PMID- 22076628 TI - [For a responsible, and detached, professional work in times of crisis. A very technical update: remembering "Essay on lucidity and blindness of J. Saramago]. AB - The leading question of this paper is whether it makes any sense, is credible or feasible to adopt aims of sensibleness and rationalization in the health care system (so strictly connected to the social and economical sector) while the criteria used by the social, economical and cultural contexts (nationally and internationally) are based on the denial of evidences, on misinterpretation of data. Some arbitrary and difficult to justify decisions are glossed over with labels of rigour and planning. Four scenarios (the role of the evidences; the global health, the mental health and the role of citizens-leading or passive role) allow to propose some provocative reflections, backed up by the most recent articles published on the most important international medical journals. PMID- 22076627 TI - [The management of insulin administration: systematic review and recommendations]. AB - AIMS: In spite of the large prevalence and increasing incidence of diabetes, recommendations on how to correctly administer the insulin are lacking. METHODS; A systematic literature review was performed starting from a list of clinical questions collected from patients, clinical experts (doctors and nurses) and others involved in diabetic patients care. The main databases were searched with the following key-words: Insulin/administration and dosage[Mesh]; "Injections, Subcutaneous/instrumentation"[Mesh]; "Injections, Subcutaneous/methods"[Mesh]; insulin administration modalities [All Fields]; insulin administration technique [All Fields]; insulin adsorption[All Fields]; Patient education as a topic/methods [Mesh]. The articles were independently analyzed by three authors and discrepancies discussed. A list of recommendations was produced weighting the evidences according to the Italian National Program for Guidelines method. RESULTS: Over 94 eligible articles, 71 were included. Recommendations for the following areas were produced: self management and education; tools and methods for insulin administration; injection sites; injection techniques; prevention and management of complications; insulin storage; management of IV infusions. Most recommendations are of level II (a single RCT with adequate design) or III (cohort non randomized studies with concurrent or historical controls). CONCLUSIONS: Although several recommendations were identified (e.g., the importance of rotation of injection sites, the criteria for choosing the right needle and injection site according to the type of insulin and speed of absorbtion), several questions are still unanswered and would warrant further and more specific studies. PMID- 22076629 TI - [1982-2012: Thirty years of Nursing and Research]. PMID- 22076630 TI - AINTEGUMENTA-LIKE6 regulates cellular differentiation in flowers. AB - During flower development, pluripotent stem cells within the floral meristem give rise to proliferative precursor cells whose progeny eventually acquire specialized functions within each floral organ. The regulatory mechanisms by which plant cells transition from a proliferating state to a differentiated state are not well characterized. Several members of the AINTEGUMENTA-LIKE/PLETHORA (AIL/PLT) transcription factor family, including AINTEGUMENTA (ANT) and AIL6/PLT3, are important regulators of cell proliferation in flowers. To further investigate the role of AIL6 during flower development, we have characterized transgenic plants in which the coding region of AIL6 was expressed under the control of the constitutive 35S promoter (35S:cAIL6). These plants display changes in floral organ size and morphology that are associated with alterations in the pattern and duration of cell divisions within developing organs. In addition, we find that very high levels of AIL6 expression inhibit cellular differentiation. In contrast, ant ail6 double mutants display premature differentiation of floral meristem cells. These results indicate that these two transcription factors regulate both proliferation and differentiation in flowers. PMID- 22076631 TI - The invention of WUS-like stem cell-promoting functions in plants predates leptosporangiate ferns. AB - The growth of land plants depends on stem cell-containing meristems which show major differences in their architecture from basal to higher plant species. In Arabidopsis, the stem cell niches in the shoot and root meristems are promoted by WUSCHEL (WUS) and WOX5, respectively. Both genes are members of a non-ancestral clade of the WUS-related homeobox (WOX) gene family, which is absent in extant bryophytes and lycophytes. Our analyses of five fern species suggest that a single WUS orthologue was present in the last common ancestor (LCA) of leptosporangiate ferns and seed plants. In the extant fern Ceratopteris richardii, the WUS pro-orthologue marks the pluripotent cell fate of immediate descendants of the root apical initial, so-called merophytes, which undergo a series of stereotypic cell divisions and give rise to all cell types of the root except the root cap. The invention of a WUS-like function within the WOX gene family in an ancestor of leptosporangiate ferns and seed plants and its amplification and sub-functionalisation to different stem cell niches might relate to the success of seed plants, especially angiosperms. PMID- 22076632 TI - Reflections on charge state distributions, protein structure, and the mystical mechanism of electrospray ionization. AB - The connection between charge state distributions, protein structure, and mechanistic details of electrospray are discussed in relation to the emerging field of gas phase structural biology. Comparisons are drawn with the established area of enzymatic catalysis in organic solvents, which shares many similar challenges. Charge solvation emerges as a dominant force in both systems that must be dealt with to enable kinetic trapping of native structures in foreign environments. Potential methods for mediating unfavorable charge solvation effects are discussed and, ironically, do not include partial solvation by water. The importance of timescale in relation to the evolution of protein structure during the process of electrospray ionization is discussed. Finally several prospects for future endeavors are highlighted. PMID- 22076633 TI - Identification of two new arthritis severity loci that regulate levels of autoantibodies, interleukin-1beta, and joint damage in pristane- and collagen induced arthritis. AB - OBJECTIVE: Cia3 is a locus on rat chromosome 4 that regulates severity and joint damage in collagen- and pristane-induced arthritis (CIA and PIA). This study was undertaken to refine the Cia3 gene-containing interval toward gene identification and obtain insights into its mode of action. METHODS: Five DA.F344(Cia3) subcongenic rat strains were generated and studied using the PIA and CIA models. Levels of antibodies against type II collagen (both allo- and autoantibodies) were measured. Joints and synovial tissue were collected 32 days after the induction of PIA (chronic stage) for histologic and quantitative polymerase chain reaction analysis of interleukin-1beta (IL-1beta) and matrix metalloproteinase (MMP) levels. RESULTS: Three subcongenic strains sharing the centromeric Cia3d interval were protected and 2 subcongenic strains sharing the telomeric Cia3g interval, which did not overlap with Cia3d, were also protected, developing significantly less severe CIA and PIA. Normal joint architecture was preserved in DA.F344(Cia3) and DA.F344(Cia3d) congenic rats with PIA, while DA rats had pronounced synovial hyperplasia, angiogenesis, inflammatory infiltration, and bone or cartilage erosions. The DA.F344(Cia3d) and DA.F344(Cia3g) strains had significantly lower synovial levels of IL-1beta (5-fold and nearly 2-fold, respectively [the latter not reaching statistical significance]), MMP-1 (expressed predominantly in DA rats), MMP-3 (79-fold and 8-fold, respectively), and MMP-14 (21-fold and 1.4-fold, respectively) and reduced levels of pathogenic autoantibodies against type II collagen, compared with DA rats. CONCLUSION: We have identified 2 new arthritis severity and articular damage loci within Cia3. These loci regulate pathogenic processes in 2 different models of rheumatoid arthritis, and the identification of these genes has the potential to generate new targets for therapies aimed at reducing disease severity and articular damage, and may additionally have prognostic value. PMID- 22076634 TI - Adrenergic signaling controls RGK-dependent trafficking of cardiac voltage-gated L-type Ca2+ channels through PKD1. AB - RATIONALE: The Rad-Gem/Kir-related family (RGKs) consists of small GTP-binding proteins that strongly inhibit the activity of voltage-gated calcium channels. Among RGKs, Rem1 is strongly and specifically expressed in cardiac tissue. However, the physiological role and regulation of RGKs, and Rem1 in particular, are largely unknown. OBJECTIVE: To determine if Rem1 function is physiologically regulated by adrenergic signaling and thus impacts voltage-gated L-type calcium channel (VLCC) activity in the heart. METHODS AND RESULTS: We found that activation of protein kinase D1, a protein kinase downstream of alpha(1) adrenergic signaling, leads to direct phosphorylation of Rem1 at Ser18. This results in an increase of the channel activity and plasma membrane expression observed by using a combination of electrophysiology, live cell confocal microscopy, and immunohistochemistry in heterologous expression system and neonatal cardiomyocytes. In addition, we show that stimulation of alpha(1) adrenergic receptor-protein kinase D1-Rem1 signaling increases transverse-tubule VLCC expression that results in increased L-type Ca(2+) current density in adult ventricular myocytes. CONCLUSION: The alpha(1)-adrenergic stimulation releases Rem1 inhibition of VLCCs through direct phosphorylation of Rem1 at Ser18 by protein kinase D1, resulting in an increase of the channel activity and transverse-tubule expression. Our results uncover a novel molecular regulatory mechanism of VLCC trafficking and function in the heart and provide the first demonstration of physiological regulation of RGK function. PMID- 22076635 TI - Frizzled 4 regulates arterial network organization through noncanonical Wnt/planar cell polarity signaling. AB - RATIONALE: A growing body of evidence supports the hypothesis that the Wnt/planar cell polarity (PCP) pathway regulates endothelial cell proliferation and angiogenesis, but the components that mediate this regulation remain elusive. OBJECTIVE: We investigated the involvement of one of the receptors, Frizzled4 (Fzd4), in this process because its role has been implicated in retinal vascular development. METHODS AND RESULTS: We found that loss of fzd4 function in mice results in a striking reduction and impairment of the distal small artery network in the heart and kidney. We report that loss of fzd4 decreases vascular cell proliferation and migration and decreases the ability of the endothelial cells to form tubes. We show that fzd4 deletion induces defects in the expression level of stable acetylated tubulin and in Golgi organization during migration. Deletion of fzd4 favors Wnt noncanonical AP1-dependent signaling, indicating that Fzd4 plays a pivotal role favoring PCP signaling. Our data further demonstrate that Fzd4 is predominantly localized on the top of the plasma membrane, where it preferentially induces Dvl3 relocalization to promote its activation and alpha tubulin recruitment during migration. In a pathological mouse angiogenic model, deletion of fzd4 impairs the angiogenic response and leads to the formation of a disorganized arterial network. CONCLUSIONS: These results suggest that Fzd4 is a major receptor involved in arterial formation and organization through a Wnt/PCP pathway. PMID- 22076638 TI - Complications and legal outcomes of tonsillectomy malpractice claims. AB - OBJECTIVES/HYPOTHESIS: To review malpractice cases involving complications following tonsillectomy. STUDY DESIGN: Retrospective analysis at a tertiary medical center of jury verdict reports within the LexisNexis (Dayton, OH) database submitted after tonsillectomy malpractice cases. METHODS: The LexisNexis MEGA Jury Verdicts and Settlements database was reviewed from 1984 through 2010 for complications resulting from tonsillectomy. Data including year of case, surgical complication, injury, case result, and judgment awarded were collected and analyzed. RESULTS: One hundred seventy-eight reports met inclusion criteria and were reviewed. Postoperative bleeding was the most common complication (33.7%), followed by anoxic events (16.9%), and impaired function (15.7%). Patient death occurred in 40.4% of reports and was most frequently associated with postoperative bleeding (54.2%), followed by anoxic events (18.1%), and postoperative medication issues (16.7%). Monetary awards were available in 24.7% of reports. Anoxic event was noted to have the highest median award at $3,051,296, followed by postoperative medication at $950,000. CONCLUSIONS: Tonsillectomy carries a large amount of risk from a malpractice standpoint. Postoperative bleeding is the complication most commonly associated with malpractice claims, but may not carry the greatest overall risk from a patient care or monetary standpoint. Hypoxic and anoxic events, although less common, appear to carry more morbidity for the patient and are associated with greater settlements and judgments in malpractice claims. Tonsillectomy continues to carry a significant mortality risk, albeit infrequent, and a high level of vigilance should be employed to help reduce these risks. PMID- 22076637 TI - The perlecan fragment LG3 is a novel regulator of obliterative remodeling associated with allograft vascular rejection. AB - RATIONALE: Endothelial apoptosis is increased in association with acute and chronic vascular rejection (VR) of solid allografts. Apoptotic endothelial cells (EC) release LG3, a C-terminal fragment of perlecan of potential importance in vascular remodeling and neointima formation. OBJECTIVE: Our 2 goals were to determine whether circulating levels of LG3 are increased in association with acute VR of renal allografts and to evaluate the impact of LG3 on vascular remodeling. METHODS AND RESULTS: We conducted a case-control study to compare serum LG3 levels in human renal transplant patients with acute VR, tubulo interstitial rejection (ATIR) and normal graft function. Aorta transplantation between fully MHC-mismatched mice in association with intravenous LG3 injection was used to characterize the impact of LG3 on vascular remodeling. Scratch assays evaluated the promigratory activity of LG3 on vascular smooth muscle cells (VSMC) in vitro. Serum LG3 levels were significantly elevated in human renal transplant patients with acute VR (n = 16) compared to ATIR (n = 16) and normal graft function (n = 32, P = 0.004). In patients with acute VR, graft loss was associated with elevated LG3 levels. Increasing LG3 serum levels in aortic allograft recipients significantly increased neointima formation. LG3 injection fostered accumulation of alpha-smooth muscle actin-positive cells and decreased the number of CD31 positive EC. LG3 increased the migration of VSMC through extracellular signal-regulated kinases 1/2-dependent pathways. CONCLUSION: These results indicate that LG3 is a novel regulator of obliterative vascular remodeling during rejection. PMID- 22076639 TI - An O2 smart plastic film for packaging. AB - The preparation and characterisation of a novel, water-proof, irreversible, reusable, UV-activated, O(2) sensitive, smart plastic film is described. A pigment, consisting of a redox dye, methylene blue (MB), and a sacrificial electron donor, DL-threitol, coated onto an inorganic support with semiconductor functionality, TiO(2), has been extruded in low-density polyethylene (LDPE). The blue-coloured indicator is readily photobleached in <90 s using UVA light (4 mW cm(-2)), whereby MB is converted to its colourless, leuco form, leuco-methylene blue (LMB). This form persists in the absence of oxygen, but is re-oxidised to MB in ~2.5 days in air under ambient conditions (~21 degrees C, ~65% RH) within the O(2) smart plastic film. The rate of recovery is linearly dependent upon the ambient level of O(2). At the lower temperature of 5 degrees C, the kinetics of the photobleaching activation step is largely unchanged, whereas that of recovery is markedly reduced to t(1/2) = 36 h at 5 degrees C (cf. 9 h at 21 degrees C); the activation energy for the recovery step was calculated as 28 kJ mol(-1). The O(2)-sensitive recovery step was found to be moderately dependent upon humidity at 21 degrees C, but not significantly dependent upon humidity at 5 degrees C. The possible application of this type of indicator in food packaging is illustrated and discussed briefly. PMID- 22076636 TI - Integration of repulsive guidance cues generates avascular zones that shape mammalian blood vessels. AB - RATIONALE: Positive signals, such as vascular endothelial growth factor, direct endothelial cells (ECs) to specific locations during blood vessel formation. Less is known about repulsive signal contribution to shaping vessels. Recently, "neuronal guidance cues" have been shown to influence EC behavior, particularly in directing sprouting angiogenesis by repelling ECs. However, their role during de novo blood vessel formation remains unexplored. OBJECTIVE: To identify signals that guide and pattern the first mammalian blood vessels. METHODS AND RESULTS: Using genetic mouse models, we show that blood vessels are sculpted through the generation of stereotyped avascular zones by EC-repulsive cues. We demonstrate that Semaphorin3E (Sema3E) is a key factor that shapes the paired dorsal aortae in mouse, as sema3E(-/-) embryos develop an abnormally branched aortic plexus with a markedly narrowed avascular midline. In vitro cultures and avian grafting experiments show strong repulsion of ECs by Sema3E-expressing cells. We further identify the mouse notochord as a rich source of multiple redundant neuronal guidance cues. Mouse embryos that lack notochords fail to form cohesive aortic vessels because of loss of the avascular midline, yet maintain lateral avascular zones. We demonstrate that lateral avascular zones are directly generated by the lateral plate mesoderm, a critical source of Sema3E. CONCLUSIONS: These findings demonstrate that Sema3E-generated avascular zones are critical regulators of mammalian cardiovascular patterning and are the first to identify a repulsive role for the lateral plate mesoderm. Integration of multiple, and in some cases redundant, repulsive cues from various tissues is critical to patterning the first embryonic blood vessels. PMID- 22076640 TI - Preparation of diastereomerically pure dilignol model compounds. AB - A gram-scale synthetic access to diastereomerically pure dilignol beta-O-4 type model compounds, which represent valuable candidates for studies of lignin cleavage and valorization, is described. Following a straightforward procedure both diastereoisomers of 1,3-dilignols can be prepared. In the key-step, tert butyl aryloxy esters are used as enolate precursors for additions on aldehydes. After separation, the resulting erythro and threo beta-hydroxy esters are independently reduced to afford the target compounds in high yields. PMID- 22076641 TI - Design and synthesis of new 1,3-benzdiazinan-4-one derivatives as selective cyclooxygenase (COX-2) inhibitors. AB - A new group of regioisomeric 2,3-diaryl-1,3-benzdiazinan-4-ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were tested for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1/COX 2 inhibition studies identified 3-(p-fluorophenyl)-2-(4-methylsulfonylphenyl)-1,3 benzdiazinane-4-one (2b) as a potent and highly selective (IC(50) = 0.07 uM; selectivity index = 572.8) COX-2 inhibitor. PMID- 22076643 TI - Evidence-based recommendations for spine surgery. PMID- 22076644 TI - Surgery for failed cervical spine reconstruction. AB - STUDY DESIGN: Review article. OBJECTIVE: To review the indications, operative strategy, and complications of revision cervical spine reconstruction. SUMMARY OF BACKGROUND DATA: With many surgeons expanding their indications for cervical spine surgery, the number of patients being treated operatively has increased. Unfortunately, the number of patients requiring revision procedures is also increasing, but very little literature exists reviewing changes in the indications or operative planning for revision reconstruction. METHODS: Narrative and review of the literature. RESULTS: In addition to the well-accepted indications for primary cervical spine surgery (radiculopathy, myelopathy, instability, and tumor), we have used the following indications for revision surgery: pseudarthrosis, adjacent segment degeneration, inadequate decompression, iatrogenic instability, and deformity. Our surgical goal for pseudarthrosis is obviously to obtain a fusion, which can usually be performed with an approach not done previously. Our surgical goals for instability and deformity are more complex, with a focus on decompression of any neurologic compression, correction of deformity, and stability. CONCLUSION: Revision cervical spine reconstruction is safe and effective if performed for the appropriate indications and with proper planning. PMID- 22076645 TI - Transmission of force in the lumbosacral spine during backward falls. AB - STUDY DESIGN: Mathematical model, combined with and verified using human subject data. OBJECTIVE: (1) To develop and verify a lumped-parameter mathematical model for prediction of spine forces during backward falls; (2) to use this model to evaluate the effect of floor stiffness on spine forces during falls; and (3) to compare predicted impact forces with forces previously measured to fracture the spine. SUMMARY OF BACKGROUND DATA: Vertebral fractures are the most common osteoporotic fractures and commonly result from falls from standing height. Compliant flooring reduces the force at the ground during a backward fall from standing; however, the effect on spine forces is unknown. METHODS: A 6-df model of the body was developed and verified using data from 10 human subjects falling from standing onto 3 types of compliant floors (soft: 59 kN/m, medium: 67 kN/m, and firm: 95 kN/m). The simulated ground forces were compared with those measured experimentally. The model was also used to assess the effect of floor stiffness on spine forces at various intervertebral levels. RESULTS: There was less than 14% difference between model predictions and experimentally measured peak ground reaction forces, when averaged over all floor conditions. When compared with the rigid floor, average peak spine force attenuations of 46%, 43%, and 41% were achieved with the soft, medium, and firm floors, respectively (3.7, 3.9, 4.1 kN vs. 6.9 kN at L4/L5). Spine forces were lower than those at the ground and decreased cranially (4.9, 3.9, 3.7, 3.5 kN at the ground, L5/S1, L4/L5, and L3/L4, respectively, for the soft floor). CONCLUSION: Lowering the floor stiffness (from 400 to 59 kN/m) can attenuate peak lumbosacral spine forces in a backward fall onto the buttocks from standing by 46% (average peak from 6.9 to 3.7 kN at L4/L5) to values closer to the average tolerance of the spine to fracture (3.4 kN). PMID- 22076646 TI - Regression of giant cell tumor of the cervical spine with bisphosphonate as single therapy. AB - STUDY DESIGN: A case report. OBJECTIVE: To describe a case of regression of a giant cell tumor (GCT) of the cervical spine, which was treated with zoledronic acid as single therapy. SUMMARY OF BACKGROUND DATA: Bisphosphonates are antiresorptive drugs used in patients with myeloma and bone metastases to treat pain and skeletal events. Despite the emerging evidence of antitumoral effects in adjuvant therapy for GCT of bone, the use of bisphosphonates as a single agent has not been described. METHODS: Case study with follow-up examination and radiological control 36 months after the beginning of therapy. A review of the literature is also provided. RESULTS: The imaging data at admission evidenced an extensive osteolytic lesion on C5 and C6 vertebral bodies. An open biopsy confirmed the diagnosis of GCT. It was decided to immobilize the cervical spine with rigid collar and to start monthly intravenous zoledronic acid. The subsequent clinical and radiological follow-up during 3 years revealed a marked regression of the lesion. CONCLUSION: The use of a bisphosphonate agent for GCT of the cervical spine showed potential therapeutic benefits as previously described for other osteolytic disorders. This finding could lead to further investigation on the role and true value of these drugs as possible adjuvants in the management of GCT of bone. PMID- 22076647 TI - Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions. AB - STUDY DESIGN: Prospective multicenter randomized clinical trail. OBJECTIVE: The goal of our 2-year prospective study was to perform a randomized clinical trial comparing the outcomes of Grafton demineralized bone matrix (DBM) Matrix with local bone with that of iliac crest bone graft (ICBG) in a single-level instrumented posterior lumbar fusion. SUMMARY OF BACKGROUND DATA: There has been extensive research and development in identifying a suitable substitute to replace autologous ICBG that is associated with known morbidities. DBMs are a class of commercially available grafting agents that are prepared from allograft bone. Many such products have been commercially available for clinical use; however, their efficacy for spine fusion has been mostly based on anecdotal evidence rather than randomized controlled clinical trials. METHODS: Forty-six patients were randomly assigned (2:1) to receive Grafton DBM Matrix with local bone (30 patients) or autologous ICBG (16 patients). The mean age was 64 (females [F] = 21, males [M] = 9) in the DBM group and 65 (F = 9, M = 5) in the ICBG group. An independent radiologist evaluated plain radiographs and computed tomographic scans at 6-month, 1-year, and 2-year time points. Clinical outcomes were measured using Oswestry Disability Index (ODI) and Medical Outcomes Study 36 Item Short Form Health Survey. RESULTS: Forty-one patients (DBM = 28 and ICBG = 13) completed the 2-year follow-up. Final fusion rates were 86% (Grafton Matrix) versus 92% (ICBG) (P = 1.0 not significant). The Grafton group showed slightly better improvement in ODI score than the ICBG group at the final 2-year follow-up (Grafton [16.2] and ICBG [22.7]); however, the difference was not statistically significant (P = 0.2346 at 24 mo). Grafton showed consistently higher physical function scores at 24 months; however, differences were not statistically significant (P = 0.0823). Similar improvements in the physical component summary scores were seen in both the Grafton and ICBG groups. There was a statistically significant greater mean intraoperative blood loss in the ICBG group than in the Grafton group (P < 0.0031). CONCLUSION: At 2-year follow-up, subjects who were randomized to Grafton Matrix and local bone achieved an 86% overall fusion rate and improvements in clinical outcomes that were comparable with those in the ICBG group. PMID- 22076648 TI - Culture and ethnicity influence outcomes of the Scoliosis Research Society Instrument in adolescent idiopathic scoliosis. AB - STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To report preoperative differences in the Scoliosis Research Society Outcomes Instrument (SRS-30) between multiple US ethnicities and native Japanese and Korean children with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The SRS-24 was developed in a US cohort with AIS. Comparative studies using the SRS-24 between US and Japanese patients showed differences, suggesting that culture might affect functional outcome. METHODS: Preoperative SRS-30 outcomes were collected from 1853 children with AIS from 6 different ethnic groups: US white (1234), black (213), Hispanic (78), and Asian (29), as well as native Japanese (192) and Koreans (107). Analysis of covariance of 4 SRS-30 domains (pain, appearance, activity, and mental) was compared between groups adjusting for differences in age, sex, major curve magnitude, and body mass index. Pairwise comparisons of the 4 SRS-30 domains were adjusted for multiple comparisons, using Bonferroni correction. A P value of less than 0.05 was considered significant. RESULTS: Significant differences between ethnicities were found in all domains (P < 0.001). Whites reported more pain than Japanese or Koreans (Japanese = 4.52, Korean = 4.47, white = 4.04). Korean and Japanese patients had the lowest appearance scores (Japanese = 2.89, Korean = 2.73, US Asian = 3.55, Hispanic = 3.11, black = 3.47, white = 3.29). Koreans also had the lowest activity (Korean = 3.64, Japanese = 4.24, US Asian = 4.07, Hispanic = 4.02, black = 4.06, white = 4.16), mental (Korean = 3.70, Japanese = 4.23, US Asian = 4.05, Hispanic = 3.75, black = 4.03, white = 3.94), and total scores (Korean = 3.63, Japanese = 3.92, US Asian = 4.02, Hispanic = 3.75, black = 3.92, and white = 3.84). CONCLUSION: Culture and ethnicity influence SRS-30 outcomes in AIS. Whites reported more pain than Japanese and Koreans. Japanese and Koreans had the lowest appearance scores. Koreans additionally were distinguished by the lowest activity, mental, and total scores. These cultural and ethnic differences must be taken into account when counseling patients with AIS and studying functional outcomes. PMID- 22076649 TI - Intrinsic gemcitabine resistance in a novel pancreatic cancer cell line is associated with cancer stem cell-like phenotype. AB - Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal malignancies in the world, often diagnosed at an advanced stage, resistant to conventional chemotherapy and having high invasive and metastatic potential. The mechanism of drug resistance of PDA is still not clear. In the present study, we established two novel pancreatic cancer cell lines PAXC-002 and PAXC-003 from human primary xenograft models. The cell lines were characterized by morphology, karyotype, pancreatic cancer marker and short tandem repeat (STR) analysis, and growth kinetics and tumorigenicity. The in vitro anti-proliferation test revealed that PAXC-002 cell was intrinsically resistant to the standard of care chemotherapy-gemcitabine, compared with that of PAXC-003 and other widely used pancreatic cancer cell lines. Interestingly, the gemcitabine resistant PAXC-002 cell line was more potent in forming colonies in 3-Dimensional matrigel culture conditions and had a higher percentage of CD133 positive cells, which is recognized as a cancer stem cell marker, compared to the gemcitabine-sensitive PAXC-003 cell line. In this study, we present two novel pancreatic cancer cell lines which could be used for gemcitabine resistance investigation, mechanism identification of pancreatic cancer and anticancer drug screening. The preliminary data indicate that the drug resistance of pancreatic carcinoma cells is associated with a cancer stem cell-like phenotype. PMID- 22076651 TI - Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model. AB - Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP-grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells' activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications. PMID- 22076650 TI - Macrophage-tumor crosstalk: role of TAMR tyrosine kinase receptors and of their ligands. AB - Ample clinical and preclinical evidence indicates that macrophages interact with tumor cells as well as with virtually all populations of host cells present in the tumor microenvironment. This crosstalk can strongly promote malignancy, but also has in principle the potential to inhibit tumor growth. Thus, it is of the utmost importance to improve our understanding of the mechanisms driving the pro- and antimalignant behavior of tumor-associated macrophages (TAMs) in order to develop better anticancer therapies. In this review, we discuss the biological consequences of reciprocal interactions between TAMs, cancer cells, endothelial cells, fibroblasts and other leukocyte subfractions within tumors. It was recently elucidated that tumors specifically educate macrophages to secrete growth arrest-specific gene 6 (Gas6), the common ligand of the Tyro3, Axl, Mer receptor (TAMR) family. In turn, Gas6 fosters tumor growth by promoting cancer cell proliferation. Therefore, the Gas6-TAMR axis might represent a novel target for disrupting tumor-macrophage crosstalk. We summarize here what is known about TAMR and their ligands in (human) cancer biology. In order to shed more light on the role of macrophages in human cancer, we additionally provide an overview of what is currently known about the prognostic impact of TAMs in human cancer. PMID- 22076652 TI - Genetic alterations of PTEN in human melanoma. AB - The PTEN gene is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Inactivating mutations and deletions of the PTEN gene are found in many types of cancers, including melanoma. However, the exact frequency of PTEN alteration in melanoma is unknown. In this study, we comprehensively reviewed 16 studies on PTEN genetic changes in melanoma cell lines and tumor biopsies. To date, 76 PTEN alterations have been reported in melanoma cell lines and 38 PTEN alterations in melanoma biopsies. The rate of PTEN alterations in melanoma cell lines, primary melanoma, and metastatic melanoma is 27.6, 7.3, and 15.2%, respectively. Three mutations were found in both melanoma cell lines and biopsies. These mutations are scattered throughout the gene, with the exception of exon 9. A mutational hot spot is found in exon 5, which encodes the phosphatase activity domain. Evidence is also presented to suggest that numerous homozygous deletions and missense variants exist in the PTEN transcript. Studying PTEN functions and implications of its mutations and other genes could provide insights into the precise nature of PTEN function in melanoma and additional targets for new therapeutic approaches. PMID- 22076653 TI - Functional mechanisms of the cellular prion protein (PrP(C)) associated anti-HIV 1 properties. AB - The cellular prion protein PrP(C)/CD230 is a GPI-anchor protein highly expressed in cells from the nervous and immune systems and well conserved among vertebrates. In the last decade, several studies suggested that PrP(C) displays antiviral properties by restricting the replication of different viruses, and in particular retroviruses such as murine leukemia virus (MuLV) and the human immunodeficiency virus type 1 (HIV-1). In this context, we previously showed that PrP(C) displays important similarities with the HIV-1 nucleocapsid protein and found that PrP(C) expression in a human cell line strongly reduced HIV-1 expression and virus production. Using different PrP(C) mutants, we report here that the anti-HIV-1 properties are mostly associated with the amino-terminal 24 KRPKP-28 basic domain. In agreement with its reported RNA chaperone activity, we found that PrP(C) binds to the viral genomic RNA of HIV-1 and negatively affects its translation. Using a combination of biochemical and cell imaging strategies, we found that PrP(C) colocalizes with the virus assembly machinery at the plasma membrane and at the virological synapse in infected T cells. Depletion of PrP(C) in infected T cells and microglial cells favors HIV-1 replication, confirming its negative impact on the HIV-1 life cycle. PMID- 22076654 TI - Unassigned codons, nonsense suppression, and anticodon modifications in the evolution of the genetic code. AB - The origin of the genetic code is a central open problem regarding the early evolution of life. Here, we consider two undeveloped but important aspects of possible scenarios for the evolutionary pathway of the translation machinery: the role of unassigned codons in early stages of the code and the incorporation of tRNA anticodon modifications. As the first codons started to encode amino acids, the translation machinery likely was faced with a large number of unassigned codons. Current molecular scenarios for the evolution of the code usually assume the very rapid assignment of all codons before all 20 amino acids became encoded. We show that the phenomenon of nonsense suppression as observed in current organisms allows for a scenario in which many unassigned codons persisted throughout most of the evolutionary development of the code. In addition, we demonstrate that incorporation of anticodon modifications at a late stage is feasible. The wobble rules allow a set of 20 tRNAs fully lacking anticodon modifications to encode all 20 canonical amino acids. These observations have implications for the biochemical plausibility of early stages in the evolution of the genetic code predating tRNA anticodon modifications and allow for effective translation by a relatively small and simple early tRNA set. PMID- 22076655 TI - Participation and attrition in a coping skills intervention for adolescent girls with inflammatory bowel disease. AB - The current study examined factors associated with adolescent and parent participation in a coping skills intervention for adolescent girls with inflammatory bowel disease (IBD) and examined factors associated with attrition related to intermittent missing data. Thirty-one adolescent girls with IBD and their parents enrolled in the intervention. Psychosocial and disease factors related to participation in the 6-week web component of the coping skills intervention were examined as were baseline group differences between those who provided post-treatment data and those who did not. Adolescents experiencing more difficulties related to their disease and psychosocial functioning participated less in the web component of the treatment intervention. Families who attrited had higher baseline levels of parental catastrophic thoughts, parenting stress, and adolescent depression. Families experiencing greater levels of psychological and disease-related difficulties may be at risk for low participation and eventual dropout from pediatric IBD psychological treatment interventions. PMID- 22076657 TI - G-protein-coupled receptor-mediated MAPK and PI3-kinase signaling is maintained in Chinese hamster ovary cells after gamma-irradiation. AB - To expedite G-protein-coupled receptor (GPCR) drug screening studies, cell lines amenable to transfection (e.g. CHO cells) have been widely used as cellular models. These cells can be frozen in a ready-to-use format, allowing screening of a single batch of cells and validation of the cellular material prior to the screening run. A common method used to deliver frozen cells to screening programs is to gamma-irradiate the cells, abrogating cell division after thawing and ensuring consistency in the number of cells analyzed per well. With the recognition that signaling proteins such as ERK and Akt are important markers of GPCR activation, along with the availability of suitable assays for their measurement, these outputs have become important for GPCR screening programs. Here we show that several gamma-irradiated and frozen CHO-K1 cell lines expressing transfected GPCRs, initially optimized for performing cAMP or AequoScreen calcium flux assays, can be used for the measurement of GPCR-mediated ERK and Akt phosphorylation. Furthermore, CHO-K1 cells transfected with NOP or GAL(1) receptors show pharmacology for a number of agonists and antagonists that is consistent with non-irradiated cultured lines. These data indicate that gamma irradiated CHO-K1 cells can be reliably used for the measurement of GPCR-mediated kinase signaling outputs. PMID- 22076658 TI - Original report of bilateral carotid body tumors with 2 rare concomitant anatomic findings, an ectopic parathyroid gland and cervical thymus, with literature review. AB - BACKGROUND: Carotid body tumors are uncommon neoplasms with unique epidemiology and management demands. Cervical embryology is complex. Developmental abnormalities can result in ectopic displacement of native tissues. METHODS: We present the case of a 21-year-old female with bilateral carotid body paragangliomas who presented to our clinic seeking excision of the symptomatic right-sided tumor. RESULTS: The patient was successfully treated with surgical excision. Two rare anatomic variants were identified in her surgical specimen: a carotid sheath parathyroid gland and ectopic thymus tissue. CONCLUSIONS: This patient represents an unreported combination of pathologic and anatomic phenomena. The paraganglioma resulted from a familial genetic mutation that is well studied in this patient's ethnic population (Dutch), and the literature on this topic is reviewed herein. The 2 anatomic variants likely represent a single, embryologic glitch that will carry no physiologic sequelae. The clinical application of this ectopic anatomy and the common embryologic origins are discussed. PMID- 22076656 TI - Perfectionism dimensions and dependency in relation to personality vulnerability and psychosocial adjustment in patients with coronary artery disease. AB - The present study sought to illuminate self-criticism and personal standards dimensions of perfectionism and dependency as specific cognitive-personality vulnerability factors that might contribute to a better understanding of numerous psychosocial problem areas that are relevant to coronary artery disease (CAD). One hundred and twenty-three patients diagnosed with clinically significant CAD completed self-report questionnaires. Zero-order correlations and factor analysis results revealed that self-criticism was primarily related to personality vulnerability (aggression/anger/hostility, Type D negative affectivity) and psychosocial maladjustment (depressive symptoms, worry, avoidant coping, support dissatisfaction), whereas personal standards was primarily related to adaptive coping (problem-focused coping, positive reinterpretation) and dependency was primarily related to worry. Hierarchical regression results demonstrated the incremental utility of self-criticism, personal standards, and dependency in relation to (mal)adjustment over and above aggression/anger/hostility, negative affectivity, and social inhibition. Continued efforts to understand the role of perfectionism dimensions and dependency in CAD appear warranted. PMID- 22076659 TI - Protein disorder in the centrosome correlates with complexity in cell types number. AB - Here we study the properties and the evolution of proteins that constitute the Centrosome, the complex molecular assembly that regulates the division and differentiation of animal cells. We found that centrosomal proteins are predicted to be significantly enriched in disordered and coiled-coil regions, more phosphorylated and longer than control proteins of the same organism. Interestingly, the ratio of these properties in centrosomal and control proteins tends to increase with the number of cell-types. We reconstructed indels evolution, finding that indels significantly increase disorder in both centrosomal and control proteins, at a rate that is typically larger along branches associated with a large growth in cell-types number, and larger for centrosomal than for control proteins. Substitutions show a similar trend for coiled-coil, but they contribute less to the evolution of disorder. Our results suggest that the increase in cell-types number in animal evolution is correlated with the gain of disordered and coiled-coil regions in centrosomal proteins, establishing a connection between organism and molecular complexity. We argue that the structural plasticity conferred to the Centrosome by disordered regions and phosphorylation plays an important role in its mechanical properties and its regulation in space and time. PMID- 22076660 TI - Palladium-catalyzed oxidative arylalkylation of activated alkenes: dual C-H bond cleavage of an arene and acetonitrile. AB - Not one but two: The title reaction proceeds through the dual C-H bond cleavage of both aniline and acetonitrile. The reaction affords a variety of cyano-bearing indolinones in excellent yield. Mechanistic studies demonstrate that this reaction involves a fast arylation of the olefin and a rate-determining C-H activation of the acetonitrile. PMID- 22076661 TI - Psychiatric adverse drug reactions reported during a 10-year period in the Swedish pediatric population. AB - PURPOSE: Psychiatric Adverse Drug Reactions (ADRs) are frequent in the pediatric population. The aim of the present study was to analyze spontaneously reported psychiatric ADRs in children during a 10-year period. METHODS: All spontaneously reported Individual Case Safety Reports (ICSRs) concerning children (<18 years old) and psychiatric adverse reactions assessed as at least possible, registered in the Swedish Drug Information System (SWEDIS) during the period 2001-2010, were extracted and characterized. Age and sex distribution and labeling/registration status were studied. RESULTS: A total of 600 ICSRs concerning 744 psychiatric adverse reactions were identified and included in the analysis. Boys were overrepresented among included ICSRs (60.3% vs. 39.7%; p < .001). After exclusion of vaccines, the three most frequently suspected drugs were montelukast, centrally working sympathomimetic drugs, and inhaled glucocorticoids. Serious adverse reactions were reported more frequently for drugs used off-label than for drugs used according to the Swedish Physician's Desk Reference. Aggressiveness was reported more frequently for boys than for girls as were suicidal conditions. CONCLUSIONS: Psychiatric ADRs in the pediatric population have been reported for a wide range of reactions and drugs and display age and sex differences including a higher number of suicidal reactions in boys. An association was seen between serious reactions and off-label drug use. Further studies are needed to elucidate safety aspects of unlicensed drugs and drugs used off-label and whether there are differences in children's susceptibility to develop ADRs. PMID- 22076662 TI - The moderating role of father's care on the onset of binge eating symptoms among female late adolescents with insecure attachment. AB - The present study examined the association between quality of attachment, perception of the father's bond, and binge eating symptoms in a sample of female late adolescents. In total, 233 female students aged between 18 and 20 years completed measures on binge eating, quality of attachment and parent-child relationship. Data showed that respondents with binge symptoms reported lower scores on secure attachment and father's care, and higher scores on preoccupied and fearful attachment. Binge eating symptoms were associated with father's care, but not with father's overprotection. Also, binge symptoms were negatively associated with secure attachment styles, and positively with preoccupied and fearful attachment. The data, finally, provided evidence that at higher levels of preoccupied attachment, the impact of binge symptoms tended to be lower when father's care was high. PMID- 22076663 TI - Fattening performance of purebred and crossbred lambs from fat-tailed Kurdi ewes mated to four Iranian native ram breeds. AB - A crossbreeding experiment was carried out to determine the sire breed effects on fattening performance of fat-tailed lambs. Rams from four Iranian fat-tailed sheep breeds, namely Kurdi (K), Afshari (A), Chaal (C) and Sanjabi (S) were mated to Kurdi ewes producing 454 progeny of four genotype groups (KK, AK, CK and SK). A total of 80 lambs comprising ten female and ten male lambs from each genotype group were used in a fattening experiment during a period of 88 days. Genotype of the lamb had significant effect on average dry matter intake (ADMI) (P < 0.05). SK lambs had the lowest ADMI. Average daily gain (ADG) and food conversion ratio (FCR) were not influenced by genotype of the lamb. Sex of the lamb had significant effect on both ADG and FCR (P < 0.01). Slaughter weight (SLW), hot carcass weight (HCW), cold carcass weight (CCW) and daily carcass gain (DCG) were not affected by lamb's genotype. However, genotype had significant effect on dressing percentage, carcass loss percentage (P < 0.01), carcass length (CL), leg circumference (LC), carcass compactness (CC) (P < 0.01) and carcass density (CD) (P < 0.05). Carcass width (CW) and leg length (LL) were not affected by lamb's genotype. Sex of the lamb had significant effects on CL, CW, LC, CC, CD (P < 0.01) and LL (P < 0.05). The results indicated the existence of sire breed difference for daily dry matter intake and carcass conformation in the fat-tailed sheep. PMID- 22076664 TI - Luis Manuel Justino Schwalbach (1966-2011). PMID- 22076665 TI - Synthesis and herbicidal activities of novel 3-(substituted benzyloxy or phenoxy) 6-methyl-4-(3-trifluoromethylphenyl)pyridazine derivatives. AB - BACKGROUND: 4-(3-Trifluoromethylphenyl)pyridazine represents a new series of compounds with bleaching and herbicidal activities. RESULTS: A total of 43 novel 3-(substituted benzyloxy or phenoxy)-6-methyl-4-(3 trifluoromethylphenyl)pyridazine derivatives were synthesised, and their bleaching and herbicidal activities were evaluated through Spirodela polyrrhiza and greenhouse tests. Some compounds exhibited excellent herbicidal activities, even at a dose of 7.5 g ha(-1). CONCLUSION: The results showed that a substituted phenoxy group at the 3-position of the pyridazine ring and the electron withdrawing group at the para-position on the benzene ring were essential for high herbicidal activity. PMID- 22076666 TI - Portal vein resection in pancreaticoduodenectomy (with video). AB - Superior mesenteric vein (SMV) resection during pancreaticoduodenectomy (PD) for pancreatic cancer was first reported by Moore in 1951. In Japan, utilization of portal vein resection (PVR) became popular beginning in the late 1970s and has resulted in an improved resection rate for pancreatic cancer. Outcomes of PVR differ according to the reported year and institution. In a recent report of meta analysis, there was no difference in outcomes after PVR if R0 (negative surgical margins) resection was possible. Pancreatic surgery including vascular resection must be re-evaluated in light of recent advances in diagnostic imaging and surgical techniques, lower mortality and morbidity after PVR, and improvements in adjuvant and neo-adjuvant therapy. Isolated portal vein involvement should not be a contraindication to resection. Portal vein resection should be considered after appropriate patient selection based on an accurate diagnosis, provided that safe R0 resection is possible. We describe technical details and considerations for PVR during PD in this paper. PMID- 22076667 TI - Distal pancreatectomy (with video). AB - Distal pancreatectomy is indicated for lesions in the pancreatic body and tail. Understanding of the anatomical structure of the pancreas and its surroundings is required in various situations in left upper abdominal surgery including the laparoscopic approach. Spleen-preserving distal pancreatectomy is indicated for lesions confined to the pancreas. Two major spleen-preserving procedures reported are the Warshaw procedure that conserves the spleen by blood flow from the short gastric vessels and the Kimura procedure that preserves the spleen with splenic vessels. Considering the laparoscopic approach, the surgeon may preserve splenic vessels from the median toward the splenic hilum without mobilization of the spleen. A standard distal pancreatectomy using the medial approach is presented on video. The intraoperative complications of distal pancreatectomy can be minimized by avoiding splenic capsule injury, by careful differentiation of the splenic artery from the common hepatic artery, and by secure closure of the splenic vein stump. The incidence of postoperative pancreatic fistula following distal pancreatectomy is reported to be 13% in a nationwide pancreatic cancer registry. Based on the results of an international randomized trial of hand-sewn and staple closure of the pancreatic stump, the closure method of the pancreatic stump can be the surgeon's choice. PMID- 22076668 TI - Stented pancreaticojejunostomy (with video). AB - BACKGROUND/PURPOSE: Using a standardized technique for pancreaticojejunostomy that we term "pair-watch suturing technique", we prospectively analyzed the effects of a pancreatic stent tube for preventing pancreatic fistula and furthermore evaluated which perioperative factors had an influence on the development of pancreatic fistula. OPERATIVE PROCEDURE: Before anastomosis, we imagine the faces of a pair of wristwatches on the jejunal hole and pancreatic duct. The first stitch was put between 9 o'clock on the pancreatic side and 3 o'clock on the jejunal side, and a total of 7 stitches were put in the posterior wall, followed by 5 stitches in the anterior wall. Using this technique, twelve stitches can be sutured in the first layer anastomosis regardless of the caliber of the pancreatic duct. PATIENTS AND METHODS: From March 2007 to April 2009, 55 consecutive patients who underwent the pair-watch suturing technique were divided into two groups: stent (n = 28) and no-stent (n = 27). The incidence rate of pancreatic fistula was statistically analyzed. From March 2007 to March 2011, 102 consecutive patients were retrospectively divided into two groups according to the International Study Group on Pancreatic Fistula criteria: postoperative pancreatic fistula (POPF) and non-POPF. RESULTS: Perioperative factors were almost the same between the stent and no-stent groups, and the incidence of pancreatic fistula was very similar: 10.7% in the stent group and 14.8% in the no stent group. Additionally, all patients who developed pancreatic fistula belonged to grade A. Among 102 patients, 15 (14.7%) were identified as having pancreatic fistula: 9 (8.8%) in grade A, 5 (4.9%) in grade B, and 1 (0.9%) in grade C. Comparing the POPF and non-POPF groups, we could not detect any significant risk factors for the development of pancreatic fistula. CONCLUSION: We consider that the pair-watch suturing technique is less susceptible to any factors, providing reliable anastomosis for any size of pancreatic duct and any texture of remnant pancreas. PMID- 22076669 TI - Important technical remarks on distal pancreatectomy with en-bloc celiac axis resection for locally advanced pancreatic body cancer (with video). AB - BACKGROUND: We have already reported the feasibility, safety, and excellent long term results of distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) for locally advanced pancreatic body cancer. An international standard for the surgical technique of DP-CAR has yet to be established. METHODS: DP-CAR was carefully performed in 42 patients in Hokkaido University Hospital from 1998 to July 2007. Arterial blood flow alteration and collateral flow development toward the liver and stomach was obtained following preoperative routine transcatheter arterial embolization of the common hepatic artery. The right-sided approach to the superior mesenteric artery and celiac artery, and the preservation of the inferior pancreatoduodenal artery during the dissection of the plexus around the pancreatic head, are the key techniques in DP-CAR. RESULTS: The operative morbidity and mortality were 43 and 4.8%, respectively. R0 resection could be done in 39 (93%) patients. Median operation time and intraoperative blood loss were 478 min and 1030 ml, respectively. Ischemic gastropathy was complicated in 5 (12%) patients, but liver abscess was found in only one patient and no liver failure was encountered. CONCLUSIONS: We emphasize again the feasibility and safety of DP-CAR; it should be a treatment of choice for locally advanced pancreatic body cancer. PMID- 22076670 TI - Left hepatectomy or left trisectionectomy with resection of the caudate lobe and extrahepatic bile duct for hilar cholangiocarcinoma (with video). AB - PURPOSE: Although left-sided hepatectomy, such as a left hepatectomy or left trisectionectomy with resection of the caudate lobe and extrahepatic bile duct, is used to treat hilar cholangiocarcinoma predominantly involving the left side of the hepatic hilum, it is associated with several difficult technical points. The important points during left-sided hepatectomy are described here. TECHNIQUES: There are anatomical variations of the sectional artery and bile duct. It is essential to understand the individual intrahepatic and hilar anatomy preoperatively. Surgical procedures consist of lymph node clearance, dissection of the distal bile duct, skeletonization resection of the hepatoduodenal ligament, mobilization of the liver and liver resection, dissection of the intrahepatic bile ducts, and biliary reconstruction. During lymph node dissection and skeletonization resection of the hepatoduodenal ligament, the nerve plexus around the hepatic artery is dissected, and its adventitia is exposed with great care to avoid injuring the hepatic artery. Mobilization of the caudate lobe is performed only from the left side. There is no clear landmark between the caudate lobe and the right posterior section during liver resection. In the final step of liver resection, it progresses toward the right edge of the inferior vena cava. When dividing intrahepatic bile ducts, extreme care should be used to avoid injury to the corresponding hepatic arteries, especially the anomalous supraportal posterior sectional artery. CONCLUSIONS: Left-sided hepatectomy for hilar cholangiocarcinoma should be considered a more complicated and technically demanding procedure than right-sided hepatectomy. Surgeons need to pay close attention to anatomical variations in order to perform a left-sided hepatectomy safely and successfully. PMID- 22076671 TI - Pancreatic dissection in the procedure of pancreaticoduodenectomy (with videos). AB - The procedure of pancreaticoduodenectomy consists of three parts: resection, lymph node dissection, and reconstruction. A transection of the pancreas is commonly performed after a maneuver of the pancreatic head, exposing of the portal vein or lymph node dissection, and it should be confirmed as a safe method for pancreatic transection for decreasing the incidence of pancreatic fistula. However, there are only a few clinical trials with high levels of evidence for pancreatic surgery. In this report, we discuss the following issues: dissection of peripancreatic tissue, exposing the portal vein, pancreatic transection, dissection of the right hemicircle of the peri-superior mesenteric artery including plexus and lymph nodes, and dissection of the pancreatic parenchyma. PMID- 22076672 TI - Cortical excitability in chronic migraine. AB - A proportion of episodic migraine patients experiences a progressive increase in attack frequency leading to chronic migraine (CM). The most frequent external factor that leads to headache chronification is medication overuse. The neurobiological bases of headache chronification and of the vicious circle of medication overconsumption are not completely elucidated. More recently, the same neurophysiological methods used to study episodic migraine were applied to CM and medication-overuse headache (MOH). Studies of cortical responsivity tend overall to indicate an increase in excitability, in particular of somatosensory and visual cortices, reflected by increased amplitude of evoked responses, decreased activity of inhibitory cortical interneurons reflected in the smaller magnetic suppression of perceptual accuracy, and, at least for visual responses, an increase in habituation. In MOH, overconsumption of triptans or NSAIDs influences cortical excitability differently. Generalized central sensitization is suggested to play an important role in the pathophysiology of headache chronification. PMID- 22076673 TI - Obesity and chronic daily headache. AB - Obesity may be the greatest epidemic of modern times. It leads to diabetes and heart disease and shortens lifespan. Although not a risk factor for migraine, it is associated with an increased frequency and intensity of migraine. Obesity is also comorbid with chronic daily headache and is a major risk factor for chronification of episodic migraine in adults and children. Although obesity is not a factor in the effectiveness of migraine treatment, it does increase the peripheral and central events in migraine, ultimately increasing the neurologic potential for migraine. Although evidence suggests that obesity is a modifiable risk factor for migraine progression, it is unknown if weight loss is related to decrease in headache frequency. Recent surgical results suggest that this is true. We suggest all possible effective techniques aimed at weight loss be undertaken for migraineurs, especially obese migraineurs, and that carefully monitoring weight changes should be routinely done as part of their migraine care. PMID- 22076674 TI - Pathophysiology of medication-overuse headache: implications from animal studies. AB - Recent animal experiments have shown that chronic medication exposure profoundly affects the function of several areas in the nervous system related to headache pathogenesis. These changes include upregulation of calcitonin gene-related peptide, substance P, and nitric oxide synthase in trigeminal ganglia; expansion of receptive field and decreased nociceptive threshold of central trigeminal neurons; decrease in diffuse noxious inhibitory control; and increased susceptibility to develop cortical spreading depression (CSD). These changes indicate an increase in excitability of cortical and trigeminal neurons. The neuronal hyperexcitability may be the result of derangement of a central, possibly serotonin (5-HT)-dependent, modulating control system. Experiments with animals with low 5-HT showed that the processes of CSD and trigeminal nociception are enhanced in this condition. Derangement in the central 5-HT-dependent modulating system as a result of chronic medication use may underlie the chronification of headache as observed in patients with medication-overuse headache. PMID- 22076675 TI - Zinc and its role in age-related inflammation and immune dysfunction. AB - Zinc is an essential micronutrient required for many cellular processes, especially for the normal development and function of the immune system. Zinc homeostasis and signaling are critical in immune activation, and an imbalance in zinc homeostasis is associated with the development of chronic diseases. Zinc deficiency causes significant impairment in both adaptive and innate immune responses, and promotes systemic inflammation. The elderly are a population particularly susceptible to zinc deficiency. National surveys indicate that a significant portion of the aged population has inadequate zinc intake, and a decline in zinc status is observed with age. There are remarkable similarities between the hallmarks of zinc deficiency and immunological dysfunction in aged individuals. Both zinc deficiency and the aging process are characterized by impaired immune responses and systemic low grade chronic inflammation. It has been hypothesized that age-related zinc deficiency may be an important factor contributing to immune dysfunction and chronic inflammation during the aging process. In this review, we discuss the effects of zinc status on aging, potential molecular and epigenetic mechanisms contributing to age-related decline in zinc status, and the role of zinc in age-related immune dysfunction and chronic inflammation. PMID- 22076677 TI - Clinical results of posterior stabilization without decompression for thoracolumbar burst fractures: is decompression necessary? AB - The purpose of this study is to investigate the clinical outcome of posterior stabilization without decompression for thoracolumbar burst fractures. Thirty-one consecutive cases of thoracolumbar fractures involving T11-L2 stabilized by a pedicle screw system were reviewed. Neither reduction of the height of a fractured body nor any decompression procedure was added during surgery. Twenty two patients had incomplete paraplegia; one patient had complete paraplegia. Neurological recovery and remodeling of the spinal canal were evaluated. Neurological status was evaluated at the time of injury, just before and after surgery, and at final follow-up. The degree of spinal canal compromise was assessed using axial CT scan images. The duration of follow-up averaged 39.6 months. The mean spinal canal compromise at the time of injury was 41.6%, and no significant correlation was observed between the degree of canal compromise and the severity of the neurological deficit. Within 2-3 weeks, spinal canal remodeling had started in all patients whose spinal canal compromise was more than 30%, and canal compromise had decreased significantly 3-4 weeks after injury. Seventeen of 22 patients with incomplete paraplegia had already shown partial neurological recovery even before surgery. At the final follow-up, all patients with incomplete paraplegia had improved by at least one modified Frankel grade. This study suggests that the effect of decompressing thoracolumbar fractures with neurological deficits remains unclear and questions the need to operate simply to remove retropulsed bone fragments. Posterior stabilization without decompression should constitute appropriate surgical treatment for these fractures. PMID- 22076676 TI - Metabolic remodeling precedes mitochondrial outer membrane permeabilization in human glioma xenograft cells. AB - Glioma cancer cells adapt to changing microenvironment and shift from mitochondrial oxidative phosphorylation to aerobic glycolysis for their metabolic needs irrespective of oxygen availability. In the present study, we show that silencing MMP-9 in combination with uPAR/cathepsin B switch the glycolytic metabolism of glioma cells to oxidative phosphorylation (OXPHOS) and generate reactive oxygen species (ROS) to predispose glioma cells to mitochondrial outer membrane permeabilization. shRNA for MMP-9 and uPAR (pMU) as well as shRNA for MMP-9 and cathepsin B (pMC) activated complexes of mitochondria involved in OXPHOS and inhibited glycolytic hexokinase expression. The decreased interaction of hexokinase 2 with mitochondria in the treated cells indicated the inhibition of glycolysis activation. Overexpression of Akt reversed the pMU- and pMC mediated OXPHOS to glycolysis switch. The OXPHOS un-coupler oligomycin A altered the expression levels of the Bcl-2 family of proteins; treatment with pMU or pMC reversed this effect and induced mitochondrial outer membrane permeabilization. In addition, our results show changes in mitochondrial pore transition to release cytochrome c due to changes in the VDAC-Bcl-XL and BAX-BAK interaction with pMU and pMC treatments. Taken together, our results suggest that pMU and pMC treatments switch glioma cells from the glycolytic to the OXPHOS pathway through an inhibitory effect on Akt, ROS induction and an increase of cytosolic cytochrome c accumulation. These results demonstrate the potential of pMU and pMC as therapeutic candidates for the treatment of glioma. PMID- 22076678 TI - Intra-operative high frequency ultrasound improves surgery of intramedullary cavernous malformations. AB - Intra-operative ultrasound (ioUS) is a very useful tool in surgery of spinal lesions. Here we focus on modern ioUS to analyze its use for localisation, visualisation and resection control in intramedullary cavernous malformations (IMCM). A series of 35 consecutive intradural lesions were operated in our hospital in a time period of 24 months using modern ioUS with a high frequency 7 15 MHz transducer and a true real time 3D transducer (both Phillips iU 22 ultrasound system). Six of those cases were treated with the admitting diagnosis of a deep IMCM (two cervical, four thoracic lesions). IoUS images were performed before and after the IMCM resection. Pre-operative and early postoperative MRI images were performed in all patients. In all six IMCM cases a complete removal of the lesion was achieved microsurgically resulting in an improved neurological status of all patients. High frequency ioUS emerged to be a very useful tool during surgery for localization and visualization. Excellent resection control by ultrasound was possible in three cases. Minor resolution of true real time 3D ioUS decreases the actual advantage of simultaneous reconstruction in two planes. High frequency ioUS is the best choice for intra-operative imaging in deep IMCM to localize and to visualize the lesion and to plan the perfect surgical approach. Additionally, high frequency ioUS is suitable for intra-operative resection control of the lesion in selected IMCM cases. PMID- 22076679 TI - Catalytic hydroboration by an imido-hydrido complex of Mo(IV). AB - The imido-hydrido complex (ArN)Mo(H)(Cl)(PMe(3))(3) catalyses a variety of hydroboration reactions, including the first example of catalytic addition of HBCat to nitriles to form the bis(borylated) amines RCH(2)N(BCat)(2). The latter species easily undergoes chemoselective coupling with aldehydes R'C(O)H to yield imines RCH(2)N=C(H)R'. PMID- 22076680 TI - Spatial and visuospatial working memory tests predict performance in classic multiple-object tracking in young adults, but nonspatial measures of the executive do not. AB - An individual-differences approach was used to investigate the roles of visuospatial working memory and the executive in multiple-object tracking. The Corsi Blocks and Visual Patterns Tests were used to assess visuospatial working memory. Two relatively nonspatial measures of the executive were used: operation span (OSPAN) and reading span (RSPAN). For purposes of comparison, the digit span test was also included (a measure not expected to correlate with tracking). The tests predicted substantial amounts of variance (R (2) = .33), and the visuospatial measures accounted for the majority (R (2) = .30), with each making a significant contribution. Although the executive measures correlated with each other, the RSPAN did not correlate with tracking. The correlation between OSPAN and tracking was similar in magnitude to that between digit span and tracking (p < .05 for both), and when regression was used to partial out shared variance between the two tests, the remaining variance predicted by the OSPAN was minimal (sr ( 2 ) = .029). When measures of spatial memory were included in the regression, the unique variance predicted by the OSPAN became negligible (sr ( 2 ) = .000004). This suggests that the executive, as measured by tests such as the OSPAN, plays little role in explaining individual differences in multiple-object tracking. PMID- 22076681 TI - Effects of temporal shapes of sound markers on the perception of interonset time intervals. AB - This study investigated how the temporal characteristics, particularly durations, of sounds affect the perceived duration of very short interonset time intervals (120-360 ms), which is important for rhythm perception in speech and music. In four experiments, the subjective duration of single time intervals marked by two sounds was measured utilizing the method of adjustment, while the markers' durations, amplitude difference (which accompanied the duration change), and sound energy distribution in time were varied. Lengthening the duration of the second marker in the range of 20-100 ms increased the subjective duration of the time interval in a stable manner. Lengthening the first marker tended to increase the subjective duration, but unstably; an opposite effect sometimes appeared for the shortest time interval of 120 ms. The effects of varying the amplitude and the sound energy distribution in time of either marker were very small in the present experimental conditions, thus proving the effects of marker durations per se. PMID- 22076682 TI - Effects of dietary copper on life-history traits of a tropical freshwater cladoceran. AB - Life-history parameters of Ceriodaphnia cornuta (Cladocera: Daphniidae) fed on Pseudokirchneriella subcapitata (Chlorophyceae) exposed to different copper concentrations were investigated. C. cornuta individuals were reared in four treatments: (a) reconstituted water and non-contaminated algae (RW); (b) reconstituted water and copper-contaminated algae with either 1.28 * 10(-13) (10( 7)Cu) or (c) 1.93 * 10(-13) g Cu cell(-1) (10(-6)Cu); and (d) natural water from a local reservoir and non-contaminated algae (NW). Copper content in C. cornuta individuals increased as diet-borne exposure increased (RW < 10(-7)Cu < NW < 10( 6)Cu), except for NW individuals, which exhibited higher copper body burden than RW and 10(-7)Cu individuals, suggesting that some copper was available in the natural water. The results suggest that subacute levels of dietary copper stimulated C. cornuta's growth and reproduction, whereas organisms reared on reconstituted water showed nutritional deficiency. Depending on copper exposure concentration, either growth (lower Cu concentration) or reproduction (higher Cu concentration) was further stimulated, suggesting that an alteration of resource allocation is involved in diet-borne copper exposure. Because differences among treatments were only significantly different after day 12 of the experiment, our results reinforce that full life-cycle tests are more appropriate than the standard 7 day or three-brood chronic bioassays used to evaluate dietary copper effects at low, chronic copper inputs and that the use of standard test-organisms may not address site-specific situations for tropical environments. PMID- 22076683 TI - Geraniol, E-3,7-dimethyl-2,6-octadien-1-ol, as the alarm pheromone of the sycamore lace bug Corythucha ciliata (Say). AB - Although adult sycamore lace bugs Corythucha ciliata (Say) show no sign of aggregation, nymphs at all developing stages are gregarious. When an individual nymph in the center of a colony was squashed with a needlepoint, proximate nymphs showed evasive behavior. The same evasive reaction was produced by exposing aggregated nymphs to nymph hexane extract. The active component, E-3,7-dimethyl 2,6-octadien-1-ol, geraniol, was responsible for the evasive behavior, and identified as the alarm pheromone. One nanogram of the alarm pheromone elicited activity similar to that in a third instar nymph. Presence of 2-acylcyclohexane 1,3-diones and their 4-hydroxy analogues are reconfirmed as nymph-specific components, though their biological significance remains unknown. PMID- 22076684 TI - A rapid, sensitive, and selective method for quantitation of lamprey migratory pheromones in river water. AB - The methodology of using fish pheromones, or chemical signatures, as a tool to monitor or manage species of fish is rapidly gaining popularity. Unequivocal detection and accurate quantitation of extremely low concentrations of these chemicals in natural waters is paramount to using this technique as a management tool. Various species of lamprey are known to produce a mixture of three important migratory pheromones; petromyzonol sulfate (PS), petromyzonamine disulfate (PADS), and petromyzosterol disulfate (PSDS), but presently there are no established robust methods for quantitation of all three pheromones. In this study, we report a new, highly sensitive and selective method for the rapid identification and quantitation of these pheromones in river water samples. The procedure is based on pre-concentration, followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. The method is fast, with unambiguous pheromone determination. Practical quantitation limits of 0.25 ng/l were achieved for PS and PADS and 2.5 ng/l for PSDS in river water, using a 200-fold pre concentration, However, lower quantitation limits can be achieved with greater pre-concentration. The methodology can be modified easily to include other chemicals of interest. Furthermore, the pre-concentration step can be applied easily in the field, circumventing potential stability issues of these chemicals. PMID- 22076685 TI - Fire injury reduces inducible defenses of lodgepole pine against Mountain pine beetle. AB - We examined the effect of wildfire injury on lodgepole pine chemical defenses against mountain pine beetle. We compared the constitutive phloem chemistry among uninjured, lightly-, moderately-, and severely-injured trees, and the induced chemistry elicited by simulated beetle attack, among these same categories. We also compared the entry rates of caged female beetles into trees of these categories. The volatiles we studied included thirteen monoterpene hydrocarbons, four allylic monoterpene alcohols, one ester, and one phenyl propanoid, of which the monoterpene hydrocarbons always comprised 96% or more of the total. Fire injury reduced the total concentration of these compounds in the induced but not constitutive phloem tissue of lodgepole pines. Fire injury also affected the relative composition of some volatiles in both induced and constitutive phloem. For example, increased fire injury reduced 4-allylanisole, a host compound that inhibits mountain pine beetle aggregation. Increased fire injury also increased ( ) alpha-pinene, which can serve as precursor of pheromone communication. However, it also reduced myrcene and terpinolene, which can serve as stimulants and synergists of pheromone communication. Beetle entry did not show statistical differences among fire injury categories, although there was a trend to increased entry with fire injury. These results suggest that the reduced ability of trees to mobilize induced chemical defenses is an important mechanism behind the higher incidence of attack on fire-injured trees in the field. Future studies should concentrate on whether beetles that enter fire-injured trees are more likely to elicit aggregation, based on the differences we observed in volatile composition. PMID- 22076686 TI - The RABL5 homolog IFT22 regulates the cellular pool size and the amount of IFT particles partitioned to the flagellar compartment in Chlamydomonas reinhardtii. AB - Cilia and flagella, sensory and motile structures protruding from the cell body, rely on the continuous bidirectional traffic of intraflagellar transport (IFT) particles to ferry flagellar precursors into flagella for assembly. Cells synthesize a large pool of IFT particle proteins in the cell body, but only a small portion engages in active transport within the flagella at any given time. The atypical small G protein Rab-like 5 (RABL5) has been shown to move in an IFT like manner in the flagella, but its function in ciliogenesis is controversial. In this report, we demonstrate that IFT22, the Chlamydomonas reinhardtii homolog of RABL5, is a bona fide IFT particle complex B subunit. Although the amount of IFT22 remains unaffected by depletion of either complex A or B, depletion of IFT22 leads to a smaller pool of both complex A and B. Strikingly, the smaller cellular pool of IFT particles does not lead to a reduced distribution of IFT particles to flagella. Instead, the amount of IFT particle proteins, including IFT22 itself, increase in the flagella. Moreover, cells over-expressing IFT22 also accumulate IFT particles in their flagella. Taken together, these data indicate that, in C. reinhardtii, IFT22 controls the cellular levels of both complex A and B, thus plays a critical role in determining the cellular availability of IFT particles. In addition, although IFT22 may not directly carry any precursors for flagellar assembly, it controls how many IFT particles participate in ferrying precursors into flagella. PMID- 22076688 TI - The caudal space in fetuses: an anatomical study. AB - PURPOSE: The caudal epidural space is a popular site for analgesia in pediatrics. High variation in blind needle placement is common during caudal epidurals, increasing the risk of intravascular and intrathecal spread. Knowledge of safe distances and angles for accessing the caudal epidural space in premature infants can improve the safety of caudal epidural blocks. METHODS: Thirty-nine fetuses with crown-heel length between 33 and 50 cm, corresponding to gestational age of 7-9 months, were included. The dorsal surface of the sacrum from the fourth lumbar vertebra to the tip of the coccyx was dissected, following which measurements were taken on dorsal surface and midsagittal sections. The angle of depression of the needle was measured using a goniometer following the two-step method of needle insertion. RESULTS: Right and left sacral cornua were palpable in 23 of 39 fetuses (58.97%). Termination of dural sac was at S2 in most of the fetuses (53.84%), whereas the apex of the sacral hiatus was at S3 in most (58.97%). The distance from the apex of the hiatus to the termination of dura ranged from 3 to 13 mm; the anteroposterior distance of the canal at the apex of the hiatus ranged from 1.72 to 4.38 mm. All sacral parameters correlated with crown-heel length except inter-cornual distance, depth of canal at hiatus, and height of sacral hiatus. CONCLUSION: Distances and angles for accessing the caudal epidural space in fetuses do not provide all parameters for safe performance of caudal epidural blocks in premature and low birth weight infants because the apex of the sacral hiatus and the termination of the dura show wide variation in location. PMID- 22076689 TI - Is there a high-risk subtype of depression in patients with coronary heart disease? AB - Depression is a risk factor for cardiac morbidity and mortality in patients with coronary heart disease, especially in those with a recent history of acute coronary syndrome. To improve risk stratification and treatment planning, it would be useful to identify the characteristics or subtypes of depression that are associated with the highest risk of cardiac events. This paper reviews the evidence concerning several putative depression subtypes and symptom patterns that may be associated with a high risk of morbidity and mortality in cardiac patients, including single-episode major depressive disorder, depression that emerges after a cardiac event, somatic symptoms of depression, and treatment resistant depression. PMID- 22076690 TI - Ligation of the intersphincteric fistula tract (LIFT) to treat anal fistula: early results from a prospective observational study. AB - BACKGROUND: Ligation of the intersphincteric tract (LIFT), a novel sphincter saving technique, has been recently described with promising results. Literature data are still scant. In this prospective observational study, we present our experience with this technique. METHODS: Between October 2010 and April 2011, 18 patients with 'complex' fistulas underwent LIFT. All patients were enrolled in the study after a physical examination including digital examination and proctoscopy. For the purpose of this pilot study, fistulas were classified as complex if any of the following conditions were present: tract crossing more than 30% of the external sphincter, anterior fistula in a woman, recurrent fistula or pre-existing incontinence. Endpoints were healing time, presence of recurrence, faecal incontinence and surgical complications. RESULTS: Ten patients were men and 8 were women; mean age was 39 years; minimum follow-up was 4 months. Three patients required drainage seton insertion and delayed LIFT. After LIFT, 1 patient experienced haemorrhoidal thrombosis. At the end of the follow-up, 15 patients (83%) healed with no recurrence. Three patients had persistent symptoms and required further surgical treatment. We did not observe postoperative worsening of continence. CONCLUSIONS: Results from our pilot study indicate that this novel sphincter-saving approach is effective and safe for treating complex anal fistula. PMID- 22076691 TI - Diastereoselective methylation of bis(N-confused porphyrinatonickel(II)): access to configurationally stable chiral bis(porphyrinoid) and non-symmetric dimers. AB - Bis- and tris(methylated) derivatives of 3,3'-bis(N-confused porphyrin) were obtained. Methylation of C21 stabilizes the geometry of the axially chiral system allowing separation of enantiomers and assignment of an absolute configuration by X-ray methods. PMID- 22076692 TI - Serological diagnosis of echinococcosis: the diagnostic potential of native antigens. AB - PURPOSE: Human alveolar (AE) and cystic echinococcosis (CE) caused by the metacestode stages of Echinococcus multilocularis and E. granulosus, respectively, lack pathognomonic clinical signs. Diagnosis therefore relies on the results of imaging and serological studies. The primary goal of this study was to evaluate the efficacy of several easy-to-produce crude or partially purified E. granulosus and E. multilocularis metacestode-derived antigens as tools for the serological diagnosis and differential diagnosis of patients suspicious for AE or CE. METHODS: The sera of 51 treatment-naive AE and 32 CE patients, 98 Swiss blood donors and 38 patients who were initially suspicious for echinococcosis but suffering from various other liver diseases (e.g., liver neoplasia, etc.) were analysed. RESULTS: According to the results of enzyme linked immunosorbent assays (ELISA), metacestode-derived antigens of E. granulosus had sensitivities varying from 81 to 97% and >99.9% for the diagnosis of CE and AE, respectively. Antigens derived from E. multilocularis metacestodes had sensitivities ranging from 84 to 91% and >99.9% for the diagnosis of CE and AE, respectively. Specificities ranged from 92 to >99.9%. Post-test probabilities for the differential diagnosis of AE from liver neoplasias, CE from cystic liver lesions, and screening for AE in Switzerland were around 95, 86 and 2.2%, respectively. Cross-reactions with antibodies in sera of patients with other parasitic affections (fasciolosis, schistosomosis, amebosis, cysticercosis, and filarioses) did occur at variable frequencies, but could be eliminated through the use of confirmatory testing. CONCLUSIONS: Different metacestode-derived antigens of E. granulosus and E. multilocularis are valuable, widely accessible, and cost-efficient tools for the serological diagnosis of echinococcosis. However, confirmatory testing is necessary, due to the lack of species specificity and the occurrence of cross-reactions to other helminthic diseases. PMID- 22076693 TI - Eclecticism as the foundation of meta-theoretical, mixed methods and interdisciplinary research in social sciences. AB - This article examines the value of "eclecticism" as the foundation of meta theoretical, mixed methods and interdisciplinary research in social sciences. On the basis of the analysis of the historical background of the concept, it is first suggested that eclecticism-based theoretical scholarship in social sciences could benefit from the more systematic research method that has been developed for synthesizing theoretical works under the name metatheorizing. Second, it is suggested that the mixed methods community could base its research approach on philosophical eclecticism instead of pragmatism because the basic idea of eclecticism is much more in sync with the nature of the combined research tradition. Finally, the Kuhnian frame is used to support the argument for interdisciplinary research and, hence, eclecticism in social sciences (rather than making an argument against multiple paradigms). More particularly, it is suggested that integrating the different (inter)disciplinary traditions and schools into one is not necessarily desirable at all in social sciences because of the complexity and openness of the research field. If it is nevertheless attempted, experience in economics suggests that paradigmatic unification comes at a high price. PMID- 22076694 TI - Effects of water stress, organic amendment and mycorrhizal inoculation on soil microbial community structure and activity during the establishment of two heavy metal-tolerant native plant species. AB - Our aim was to examine the effect of water stress on plant growth and development of two native plant species (Tetraclinis articulata and Crithmum maritimum) and on microbial community composition and activity in the rhizosphere soil, following the addition of an organic amendment, namely sugar beet residue (SBR), and/or the inoculation with an arbuscular mycorrhizal (AM) fungus, namely Glomus mosseae, in a non-sterile heavy metal-polluted soil. The AM inoculation did not have any significant effect on plant growth of both species. In T. articulata, SBR increased shoot growth, foliar P, total phospholipid fatty acids (PLFA), fungi-related PLFA, AM fungi-related neutral lipid fatty acid, bacterial gram positive/gram-negative PLFA ratio and the beta-glucosidase and dehydrogenase activities. SBR and AM inoculation increased phosphatase activity in T. articulata plants grown under drought conditions. In both plants, there was a synergistic effect between AM inoculation and SBR on mycorrhizal colonisation under drought conditions. In C. maritimum, the increase produced by the SBR on total amounts of PLFA, bacterial gram-positive-related PLFA and bacterial gram negative-related PLFA was considerably higher under drought conditions. Our results suggest that the effectiveness of the amendment with regard to stimulating microbial communities and plant growth was largely limited by drought, particularly for plant species with a low degree of mycorrhizal colonisation. PMID- 22076695 TI - Update on thermal ablation of renal cell carcinoma: oncologic control, technique comparison, renal function preservation, and new modalities. AB - Recent studies report mid- and long-term oncologic control with thermal ablation for small renal tumors to be equivalent to surgery. Comparisons of cryoablation, radiofrequency ablation (RFA), and laparoscopic approaches to percutaneous approaches report equivalent results. Studies report little or no decrease in renal function after ablation of renal tumors. These studies support the use of percutaneous thermal ablation for treatment of small renal malignancies. Studies also report that percutaneous ablation is a safe and durable treatment of the primary tumor in stage IV patients, ultrasound guidance for percutaneous ablation can be effective, and chyluria is relatively common after RFA. Results were disappointing for newer ablation techniques, including microwave, irreversible electroporation, and high-intensity focused ultrasound. These techniques require improvements before their use in place of RFA and cryoablation. The rates of diagnostic and subtype-specific renal tumor biopsies can be improved by using both aspirate and core techniques. PMID- 22076696 TI - Behavioral medicine and the health of our nation: accelerating our impact. AB - PURPOSE: A key goal of this paper is to illustrate the impact of behavioral medicine on the factors that influence population health. A second goal is to consider the delicate balance between relevance and excellence as we bring our science to bear on important social and public health problems. If we are to increase the translation of our evidence and accelerate our impact, we must increase our relevance while maintaining excellence in our scientific methods. METHODS: What are the pressing questions facing those that we would like to use our work, and how we can increase our relevance to theirs? We must work on the marriage of relevance and excellence-use rigorous methodologies, but be flexible in our approach, using study designs and methods that will get rapid yet rigorous answers to the questions that are facing practice and policy settings. CONCLUSION: We have the tools and the knowledge to impact the health of our nation. PMID- 22076698 TI - Magnetic resonance spectroscopic methods for the assessment of metabolic functions in the diseased brain. AB - Magnetic resonance spectroscopy (MRS) is a non-invasive technique that can be used to detect and quantify multiple metabolites. This chapter will review some of the applications of MRS to the study of brain functions. Typically, (1)H-MRS can detect metabolites reflecting neuronal density and integrity, markers of energy metabolism or inflammation, as well as neurotransmitters. The complexity of the proton spectrum has however led to the development of other nuclei-based methods, such as (31)P- and (13)C-MRS, which offer a broader chemical shift range and therefore can provide more detailed information at the level of single metabolites. The versatility of MRS allows for a wide range of clinical applications, of which neurodegeneration is an interesting target for spectroscopy-based studies. In particular, MRS can identify patterns of altered brain chemistry in Alzheimer's patients and can help establish differential diagnosis in Alzheimer's and Parkinson's diseases. Using MRS to follow less abundant neurotransmitters is currently out of reach and will most likely depend on the development of methods such as hyperpolarization that can increase the sensitivity of detection. In particular, dynamic nuclear polarization has opened up a new and exciting area of medical research, with developments that could greatly impact on the real-time monitoring of in vivo metabolic processes in the brain. PMID- 22076697 TI - Benefits of adherence to psychotropic medications on depressive symptoms and antiretroviral medication adherence among men and women living with HIV/AIDS. AB - BACKGROUND: Psychotropic medications are commonly used for depressive symptoms among people living with HIV/AIDS. PURPOSE: We examined the relationships between adherence to psychotropic medications, depressive symptoms, and antiretroviral adherence. METHODS: We assessed depressive symptoms among 324 people living with HIV/AIDS across a 3-month period (70% men; mean age 45 years; 90% African American). Psychotropic and antiretroviral adherence was assessed using monthly, unannounced telephone pill counts. Multiple-regression and mediation analyses were utilized to examine associations under investigation. RESULTS: Greater depressive symptoms were associated with lower antiretroviral and psychotropic medication adherence. Greater adherence to psychotropic medications regardless of medication class was positively related to higher antiretroviral adherence. Greater adherence to psychotropic medications also significantly mediated the association between depressive symptoms and antiretroviral adherence. CONCLUSIONS: This study demonstrates the benefits of adherence to psychotropic medications on both depressive symptoms and antiretroviral adherence. Future work examining psychotropic medication adherence on disease outcomes in people living with HIV/AIDS is warranted. PMID- 22076699 TI - Porous SnO2/layered titanate nanohybrid with enhanced electrochemical performance for reversible lithium storage. AB - A porous hybrid of titanate nanosheets with SnO(2) nanoparticles has been realized by an exfoliation and reassembling route. The present nanohybrid shows a large reversible capacity of 860 mA h g(-1) with a good capacity retention (about 60% retention of the initial capacity after 50 cycles). PMID- 22076700 TI - Clinical images: peripheral retinal neovascularization in the antiphospholipid antibody syndrome. PMID- 22076701 TI - Retraction. PMID- 22076703 TI - Sialadenoma papilliferum of the parotid gland: case report and review of literature. AB - Sialadenoma papilliferum is a rare benign salivary gland tumor. We present an unusual case of sialadenoma papilliferum of the parotid gland, discuss clinical presentation, diagnostic challenges, and review of the literature. A 65-year-old male smoker presented with a large, exophytic, fungating, painless mass in the tail parotid for 8 years. The tumor developed an exophytic component 2 years before presentation. The patient subsequently underwent superficial parotidectomy with facial nerve preservation. Initial pathological analysis suggested a variant of Warthin's tumor. The pathology underwent extensive internal and external review. Final diagnosis was consistent with sialadenoma papilliferum. We present the fourth reported case of sialadenoma papilliferum within the parotid gland and only the second that has presented with breach of the overlying skin. The clinical presentation may mimic an advanced parotid malignancy. However, facial nerve preservation and good surgical outcomes can be obtained. PMID- 22076704 TI - Prognostic implication of earthquake-related loss and depressive symptoms in patients with heart failure following the 2008 earthquake in Sichuan. AB - BACKGROUND: Earthquake exposure is associated with adverse consequences for cardiovascular disease. However, in the context of depressive symptoms, the prognostic significance of heart failure (HF) related to earthquake-related loss has not been characterized before. HYPOTHESIS: To determine the prognostic impact of earthquake-related loss on event-free survival in patients with HF, with depression as a modifying factor. METHODS: Depressive symptoms were assessed by using the Zung Self-Rating Depression Scale in 404 HF patients who were followed up for 2 years after the earthquake to collect data on mortality and readmission. The Kaplan-Meier method was used to compare event-free survival between patients with and without earthquake-related loss. Cox proportional hazard regression modeling was used to examine the predicted outcomes for baseline variables. RESULTS: The proportion of patients with moderate/severe depressive symptoms among the HF patients with earthquake-related loss is much higher than their counterparts (27.038% vs 17.84%, P = 0.039). Heart failure patients without loss experienced longer event-free survival than patients with loss (P = 0.002), especially among patients without depressive symptoms (P = 0.003). Meanwhile, in a Cox proportional hazard regression model, the event-free survival was associated with earthquake-related loss, left ventricular ejection fraction, depressive symptoms, and chronic obstructive pulmonary disease or asthma. CONCLUSIONS: Heart failure patients without earthquake-related loss experienced longer event-free survival than did HF patients with severe loss. Earthquake related loss was a predictor of poor outcomes in HF patients, particularly in patients without depression. PMID- 22076705 TI - Design, synthesis and cytotoxicity of novel chalcone analogs derived from 1 cyclohexylpyrrolidin-2-one and 2,3-dihydrobenzo[f]chromen-1-one. AB - Two divergent series of novel chalcone analogs, one derived from 1 cyclohexylpyrrolidin-2-one and the other derived from 1-benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1-benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC(50) values between the range of 5 and 6 uM. With an IC(50) value of 3.4 uM, compound 4g was also active against human MDA-MB-435 melanoma cells. X-ray structures of the beta hydroxy ketone product (4a) and the alpha,beta-unsaturated ketone (4h) were collected, and confirm the syn-configuration between the carbonyl moiety and the beta-vinylic proton in 4h. X-ray structures of two 1-cyclohexylpyrrolidin-2-one derivatives were also obtained, and both showed an E-configuration for the double bond. PMID- 22076706 TI - Physionomics and metabolomics-two key approaches in herbicidal mode of action discovery. AB - BACKGROUND: For novel herbicides identified in greenhouse screens, efficient research is important to discover and chemically optimise new leads with new modes of action (MoAs). RESULTS: The metabolic and physiological response pattern to a herbicide can be viewed as the result of changes elicited in the molecular and biochemical process chain. These response patterns are diagnostic of a herbicide's MoA. At the starting point of MoA characterisation, an array of bioassays is used for comprehensive physiological profiling of herbicide effects. This physionomics approach enables discrimination between known, novel or multiple MoAs of a compound and provides a first clue to a new MoA. Metabolic profiling is performed with the use of treated Lemna paucicostata plants. After plant extraction and chromatography and mass spectrometry, changes in levels of approximately 200 identified and 300 unknown analytes are quantified. Check for known MoA assignment is performed by multivariate statistical data analyses. Distinct metabolite changes, which can direct to an affected enzymatic step, are visualised in a biochemical pathway view. Subsequent target identification includes metabolite feeding and molecular, biochemical and microscopic methods. CONCLUSION: The value of this cascade strategy is exemplified by new herbicides with MoAs in plastoquinone, auxin or very-long-chain fatty acid synthesis. PMID- 22076707 TI - Lanthanide polyoxocationic complexes: experimental and theoretical stability studies and Lewis acid catalysis. AB - The [epsilon-PMo(V)(8)Mo(VI)(4)O(36)(OH)(4){Ln(III)(H(2)O)}(4)](5+) (Ln=La, Ce, Nd, Sm) polyoxocations, called epsilonLn(4), have been synthesized at room temperature as chloride salts soluble in water, MeOH, EtOH, and DMF. Rare-earth metals can be exchanged, and (31)P NMR spectroscopic studies have allowed a comparison of the affinity of the reduced {epsilon-PMo(12)} core, thus showing that the La(III) ions have the highest affinity and that rare earths heavier than Eu(III) do not react with the epsilon-Keggin polyoxometalate. DFT calculations provide a deeper insight into the geometries of the systems studied, thereby giving more accurate information on those compounds that suffer from disorder in crystalline form. It has also been confirmed by the hypothetical La->Gd substitution reaction energy that Ln ions beyond Eu cannot compete with La in coordinating the surface of the epsilon-Keggin molybdate. Two of these clusters (Ln=La, Ce) have been tested to evidence that such systems are representative of a new efficient Lewis acid catalyst family. This is the first time that the catalytic activity of polyoxocations has been evaluated. PMID- 22076708 TI - Validation of genetic sequence variants as prognostic factors in early-stage head and neck squamous cell cancer survival. AB - PURPOSE: From the published literature, we identified 23 germ line sequence variants in 17 genes from hypothesis-generating studies that were associated with prognosis of head and neck cancer, including sequence variants of DNA repair (ERCC1, ERCC4, ERCC5, MSH2, XPA, ERCC2, XRCC1, XRCC3), DNA methylation (DNMT3B), cell cycle and proliferation (CCND1, TP53), xenobiotic metabolism (GSTM1, GSTT1, CYP2D6), metastatic -potential (MMP3), immunologic (CTLA4), and growth factor pathways (FGFR4). The purpose of this study was to validate the role of these 23 sequence variants for overall (OS) and disease-free survival (DFS) in a large, comprehensive, well-annotated data set of patients with head and neck cancer. EXPERIMENTAL DESIGN: We genotyped these sequence variants in 531 patients with stage I and II radiation-treated head and neck cancer (originally recruited for an alpha-tocopherol/beta-carotene placebo-controlled secondary prevention study), and analyzed using Cox proportional hazards models, stratified by treatment arm, adjusting for clinical prognostic factors. RESULTS: Two OS associations were statistically significant for each variant allele when compared with the wild type: CTLA4: A49G [rs231775; adjusted HR (aHR), 1.32 (1.1-1.6); P = 0.01] and XRCC1: Arg339Gln [rs25487; aHR, 1.28 (1.05-1.57); P = 0.02]. Both of these sequence variants had significant results in the opposite direction as prior published literature. Two DFS associations were of borderline significance in the same direction as prior literature: ERCC2: Lys751Gln [rs13181; aHR, 0.80 (0.6 1.0); P = 0.05] and TP53: Arg72Pro [rs1042522; aHR, 1.28 (1.0-1.6); P = 0.03], comparing number of variant alleles with reference of zero variants. CONCLUSIONS: None of the prognostic sequence variants previously published was validated for OS in our patients with early-stage radiation-treated head and neck cancer, though rs1381and rs1042522 had borderline significant association with DFS. PMID- 22076709 TI - Solution-processed reduced graphene oxide films as electronic contacts for molecular monolayer junctions. PMID- 22076710 TI - Innovation and creativity in education curricula for the medical home. PMID- 22076711 TI - Medical student awareness of the Patient-centered Medical Home. AB - BACKGROUND AND OBJECTIVES: The Patient-centered Medical Home (PCMH) has come to the forefront of primary care practice redesign and can potentially improve health care outcomes and reduce costs. There are several initiatives in medical schools to teach concepts of the PCMH to students, but it is unknown what knowledge and attitudes medical students currently possess. We report students' awareness and opinions at two medical schools without comprehensive PCMH curricula. METHODS: A total of 1,408 first- through fourth-year students at both schools were invited to participate. We distributed an electronic survey to all students via institutional e-mail listserves. Descriptive statistics were used. RESULTS: A total of 359 students participated, for a response rate of 25.5%. Despite no comprehensive curricula, 40.9% students had still encountered the topic of the PCMH. Family medicine and primary care clerkships serve as the most frequent point of exposure for students. Although many students reported not understanding the overall PCMH concept, most cited "some" understanding when presented with individually defined PCMH principles with the one exception: Value based Payment. A significant portion of first-, second-, and third-year students rated learning about the PCMH by graduation as "important," while most fourth year students rated this as "somewhat important." Students performed well on one knowledge question about PCMH principles; however, 29.6% of respondents believed that primary care physicians function as gatekeepers in the PCMH model. CONCLUSIONS: Medical students appear to have limited exposure and knowledge of the PCMH concept, suggesting the need to develop curricula about the PCMH in medical schools. PMID- 22076712 TI - An evaluation of family medicine residents' attitudes before and after a PCMH innovation for patients with chronic pain. AB - BACKGROUND AND OBJECTIVES: Prior research indicates that primary care physicians have predominantly negative attitudes toward chronic pain patients, and chronic pain patients have predominantly low satisfaction with the care and treatment they receive in primary care. This current state of affairs highlights the need for Patient-centered Medical Home (PCMH) innovations for the treatment of chronic pain in primary care. The purpose of this study was to determine if a PCMH innovation for the treatment of chronic pain in a family medicine residency program can improve resident attitudes toward chronic pain patients. METHODS: From January 2010 to December 2010, 30 family medicine residents (two--three per month) participated in twice-a-month PCMH innovation for the treatment of chronic pain in primary care ("pain clinic"). De-identified data from a Likert-type measure of negative attitudes toward chronic pain patients were extracted from pain clinic evaluation information that was collected shortly before (pretest) and shortly after (posttest) the residents' pain clinic participation. Using these data, we conducted a paired-samples t test to determine if residents' negative attitudes toward chronic pain patients had improved. RESULTS: The difference between residents' pretest scores (M=51.2, SD=10.9) and posttest scores (M=45.2, SD=9.2) was significant, suggesting that residents' negative attitudes toward chronic pain patients improved after participating in pain clinic. CONCLUSIONS: A PCMH innovation for the treatment of chronic pain in primary care can improve family medicine residents' attitudes toward chronic pain patients. PMID- 22076713 TI - Evaluation of a group prenatal care-based curriculum in a family medicine residency. AB - BACKGROUND: There is a growing trend within family medicine residency training programs to implement group prenatal care programs. While the clinical benefits of group prenatal care have been well documented, there have been no published studies to date evaluating the educational impact of using group prenatal care in residency training programs. METHODS: A retrospective cohort study of both patient care performance and outcome measures over a 4-year time span in a pre- and post-intervention design in a single family medicine training program was used. RESULTS: A total of 184 women were cared for by residents educated under the old curriculum, and 195 women were cared for under the new curriculum. Patients cared for by residents under the new curriculum had significantly fewer cesarean sections compared to patients cared for under the old curriculum (17.53% versus 26.92%) and also trended toward having a lower rate of preterm births (4.15% versus 8.33%) that reached significance when controlled for parity and insurance status. CONCLUSIONS: The ultimate measure of how well we train our residents is how well they care for their patients. Our evaluation of teaching residents maternity care through group prenatal visits and the IMPLICIT quality improvement initiative found that we improved not only several processes of care outcomes but most importantly the key maternity care outcomes of cesarean section and preterm birth rates. PMID- 22076714 TI - The Patient-centered Medical Home: a new perspective for the family medicine clerkship. AB - BACKGROUND AND OBJECTIVES: The Patient-centered Medical Home (PCMH) concept, essential functions of primary care, and an appropriate primary care workforce have been shown to improve health outcomes and reduce health care costs. This paper describes a curriculum that uses the PCMH and related health policy concepts as the foundation for didactic, clinical, and self-directed elements. The PCMH-focused curriculum improved overall student clerkship ratings and maintained student performance on the National Board of Medical Education subject exam. PMID- 22076715 TI - Shared decision making: skill acquisition for year III medical students. AB - BACKGROUND: A foundation of care within a Patient-centered Medical Home (PCMH) is respect for patients' values and preferences. Shared decision making (SDM) involves a set of principles and approaches to working with patients that integrates medical information and data with the preferences, values, and support systems of individual patients facing medical decisions. The value of SDM is increasingly evidenced by the incorporation of principles of SDM into the definitions of patient-centered care and PCMHs, accountable care organizations, and the language of the Health Reform Act of 2010. METHODS: We developed and integrated a curriculum on SDM in the third-year Family Medicine Clerkship at Dartmouth Medical School. The curriculum consisted of a mix of experiential, classroom, and online experiences designed to provide students with opportunities to learn content, practice skills, and share observations from their preceptorships. RESULTS: Student feedback was an important component of evaluating the SDM curriculum. Themes identified from students' reflections on their own behavior in a Simulated Patient Encounter included an increase in confidence and competence in their ability to use SDM, while noting the disconnect that may exist between what is taught in the clerkship and what they experience in their preceptorships. CONCLUSIONS: As this curriculum has developed, we have acquired a deep appreciation of the benefits and challenges of attempting to teach sophisticated communication and decision-making precepts to medical students who are working to master fundamentals of clinical work and who may or may not see such precepts reinforced in practice. PMID- 22076716 TI - Applying health information technology and team-based care to residency education. AB - BACKGROUND AND OBJECTIVES: Training physicians capable of practicing within the Patient-centered Medical Home (PCMH) is an emerging area of scholarly inquiry within residency education. This study describes an effort to integrate PCMH principles into teaching practices within a university-based residency setting and evaluates the effect on clinical performance. METHODS: Using participant feedback and clinical data extracted from an electronic clinical quality management system, we retrospectively examined performance outcomes at two family medicine residency clinics over a 7-year period. Instructional approaches were identified and clinical performance patterns analyzed. RESULTS: Alumni ratings of the practice-based curriculum increased following institution of the PCMH model. Clinical performance outcomes indicated improvements in the delivery of clinical care to patients. Implementation of instructional methodologies posed some challenges to residency faculty, particularly in development of consistent scheduling of individualized feedback sessions. Residents required the greatest support and guidance in managing point-of-care clinical reminders during patient encounters. CONCLUSIONS: Teaching practices that take into consideration the integration of team-based care and use of electronic health technologies can successfully be used to deliver residency education in the context of the PCMH model. Ongoing assessment provides important information to residency directors and faculty in support of improving the quality of clinical instruction. PMID- 22076717 TI - Assessing teamwork: a reliable five-question survey. AB - BACKGROUND AND OBJECTIVES: Currently available tools to measure teamwork, an essential component of primary care, are generally very resource intensive and thus cannot be administered frequently. To explore the possibility of developing a brief teamwork-assessment instrument, we first administered 29 questions about teamwork from the Practice Environment Checklist (PEC) to all members of six clinical teams in a residency outpatient practice (n=56). We found that the scale assessed a single dimension of teamwork and that a five item survey has acceptable reliability (Cronbach alpha=0.89). In a subsequent validation study among an expanded sample of clinic staff (n=89), we found that the five-item questionnaire could be completed in less than 3 minutes. It continued to have an acceptable internal consistency (Cronbach alpha=0.82) and that all five items had sizeable item-total correlations. The resulting short form of the PEC may be useful for frequent assessment of team function. PMID- 22076718 TI - Performance enhancement using a balanced scorecard in a Patient-centered Medical Home. AB - BACKGROUND AND OBJECTIVES: Oregon Health & Science University Family Medicine implemented a balanced scorecard within our clinics that embraces the inherent tensions between care quality, financial productivity, and operational efficiency. This data-driven performance improvement process involved: (1) consensus-building around specific indicators to be measured, (2) developing and refining the balanced scorecard, and (3) using the balanced scorecard in the quality improvement process. Developing and implementing the balanced scorecard stimulated an important culture shift among clinics; practice members now actively use data to recognize successes, understand emerging problems, and make changes in response to these problems. Our experience shows how Patient-centered Medical Homes can be enhanced through use of information technology and evidence based tools that support improved decision making and performance and help practices develop into learning organizations. PMID- 22076719 TI - Make room for teaching in the Patient-centered Medical Home. PMID- 22076720 TI - Meeting women's needs in the PCMH: stories from practice. PMID- 22076721 TI - How to integrate the PCMH concept. PMID- 22076722 TI - New ACGME resident duty hour impacts neurology and family medicine residents alike. PMID- 22076724 TI - Controlled synthesis of novel cyanopropyl polysilsesquioxane hollow spheres loaded with highly dispersed Au nanoparticles for catalytic applications. AB - The design and synthesis of novel cyanopropyl polysilsesquioxane hollow spheres lead to production of a highly active and stable catalyst in the reduction of 4 nitrophenol catalyzed by Au nanoparticles. PMID- 22076723 TI - Visualization and functional analysis of the oligomeric states of Escherichia coli heat shock protein 70 (Hsp70/DnaK). AB - The molecular chaperone DnaK binds to exposed hydrophobic segments in proteins, protecting them from aggregation. DnaK interacts with protein substrates via its substrate-binding domain, and the affinity of this interaction is allosterically regulated by its nucleotide-binding domain. In addition to regulating interdomain allostery, the nucleotide state has been found to influence homo-oligomerization of DnaK. However, the architecture of oligomeric DnaK and its potential functional relevance in the chaperone cycle remain undefined. Towards that goal, we examined the structures of DnaK by negative stain electron microscopy. We found that DnaK samples contain an ensemble of monomers, dimers, and other small, defined multimers. To better understand the function of these oligomers, we stabilized them by cross-linking and found that they retained ATPase activity and protected a model substrate from denaturation. However, these oligomers had a greatly reduced ability to refold substrate and did not respond to stimulation by DnaJ. Finally, we observed oligomeric DnaK in Escherichia coli cellular lysates by native gel electrophoresis and found that these structures became noticeably more prevalent in cells exposed to heat shock. Together, these studies suggest that DnaK oligomers are composed of ordered multimers that are functionally distinct from monomeric DnaK. Thus, oligomerization of DnaK might be an important step in chaperone cycling. PMID- 22076727 TI - Perception of social participation in borderline personality disorder. AB - Interpersonal dysfunction is a key feature of borderline personality disorder (BPD). Distorted perception of participation in social situations and altered emotional responses could contribute to these typical interpersonal problems in BPD. Thirty patients with BPD were compared with a healthy control group (n = 30) in their perceptions and subjective emotional reactions to situations of social inclusion and exclusion. Participants played Cyberball, a virtual ball-tossing paradigm, in which social inclusion and exclusion are experimentally induced. Control participants reacted with an increase in sadness, anger and overall negative affect when excluded. In BPD patients, social exclusion also induced anger, while general participating in the game seemed to reduce levels of sadness. Compared with healthy controls, BPD patients felt more readily excluded independent of the condition of inclusion or exclusion. In conclusion, patients with BPD displayed a negative bias toward perceived participation in social situations. Key PRACTITIONER MESSAGE: Patients with BPD have a biased perception for exclusion. Virtual ball-tossing games can be used to induce anger in patients with BPD. Participating in a virtual ball-tossing game may reduce levels of sadness in BPD in the short term. PMID- 22076726 TI - Rituximab therapy for systemic vasculitis associated with rheumatoid arthritis: Results from the AutoImmunity and Rituximab Registry. AB - OBJECTIVE: Rituximab improves articular symptoms in rheumatoid arthritis (RA) and it recently has been shown to be an effective induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis. We assessed the efficacy and safety of rituximab in a real-life clinical setting among patients with systemic rheumatoid vasculitis (SRV). METHODS: We analyzed data from the AutoImmunity and Rituximab registry, which includes patients with autoimmune diseases treated with rituximab. RESULTS: Of the 1,994 patients with RA enrolled in the registry, 17 were treated with rituximab for active SRV. At baseline, the mean Birmingham Vasculitis Activity Score for RA (BVAS/RA) was 9.6, with a mean prednisone dosage of 19.2 mg/day. After 6 months of rituximab therapy, 12 patients (71%) achieved complete remission of their vasculitis, 4 had a partial response, and 1 died with uncontrolled vasculitis. Mean BVAS/RA was reduced to 0.6 and mean prednisone dosage to 9.7 mg/day. At 12 months, 14 patients (82%) were in sustained complete remission. Severe infection occurred in 3 patients, corresponding to a 6.4 per 100 patient-years rate. In the 6 patients who received further rituximab as maintenance therapy between months 6 and 12, no relapse of vasculitis was observed. However, among the 9 patients who did not, a relapse was observed in 3 patients who were treated with methotrexate alone. Remission was reestablished by reintroducing rituximab in 2 cases. CONCLUSION: Complete remission of SRV was achieved in nearly three-fourths of patients receiving rituximab in daily practice, with a significant decrease in daily prednisone dosage and an acceptable toxicity profile. Rituximab represents a suitable therapeutic option to induce remission in SRV, but maintenance therapy seems to be necessary. PMID- 22076728 TI - Intraosseous capillary haemangioma of a metacarpal bone. PMID- 22076729 TI - First interosseous-plasty: a technique to reconstruct the radial collateral ligament of the MCP-joint of the index finger. PMID- 22076730 TI - Finger replantations after ring avulsion amputations. AB - The aim of this retrospective cross-sectional study was to assess vascular repair modalities and function in type IV ring finger replantations. Thirty-seven of 43 patients with complete ring avulsion amputations were replanted. After resection of the damaged arterial segments under microscopic magnification the arterial flow pattern was evaluated. The type of repair was chosen according to the adequacy of arterial flow and the defect between the vessels. The methods of bridging the arterial defect consisted of digital artery transfer from adjacent digit in 21 fingers, vein graft interposition in six fingers and end to end anastomosis in ten fingers. Thirty-one of the 37 fingers survived. The failures were due to four arterial and two venous insufficiencies. In our opinion, radical resection of damaged zones of vessels is important to evaluate the proximal flow pattern and decide which treatment modality is necessary for healthy vascular anastomosis. PMID- 22076731 TI - The effects of humidity and serum on the surface microhardness and morphology of five retrograde filling materials. AB - The purpose of this study was to compare the surface morphology and surface hardness of five materials 24 h after filling, in conditions of 100% humidity, and fetal bovine serum. The five materials were ProRoot Mineral Trioxide Aggregate (MTA), Super-EBA, Intermediate Restorative Materials (IRM), Zinc Oxide Eugenol (ZOE), and Amalgam. The microhardness of these materials was evaluated by Vickers microhardness test, and their morphologies were compared by using scanning electron microscopy (SEM). To evaluate the microhardness, the mixed five materials were measured with Vickers microhardness test. Differences between the experimental groups were analyzed by two-way ANOVA and Duncan's multiple comparison tests. All analyses were performed using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL). For the microstructural morphological evaluation, the cross cut and root-end cavity prepared surfaces followed by retrograde filling with five different materials were observed under a Scanning Electron Microscope (Steroscan 440; Leica, Cambridge, England) at *500. To summarize, Super EBA was less influenced by storage medium than the other materials, especially MTA. However, further long-term studies considering other factors, such as biocompatibility (i.e. cellular toxicity) and retention, are needed to be collaborated with these findings in the clinical context. PMID- 22076732 TI - Metal element excretion in 24-h urine in patients with Wilson disease under treatment of D-penicillamine. AB - Wilson disease is an inherited autosomal recessive disorder causing copper accumulation and consequent toxicity. D-Penicillamine, a potent metal chelator, is an important therapy for Wilson disease. To investigate the changes of metal elements under the treatment of D-penicillamine, we determined the levels of Cu, Zn, Mg, Ca, Fe, Se, Mn, Pb, Hg, Cd, As, Tl, and Al by ICP-MS in 24-h urine of 115 Wilson disease patients who had received treatment with D: -penicillamine for 1 month to 22 years at maintenance doses, as well as 115 age-matched, healthy controls. The levels of Cu, Mg, Ca, Zn, Hg, Pb, Tl, Cd, and Mn in the 24-h urine of the cases were significantly higher than those of the controls (P < 0.05), and the observed increases in the levels of Mg, Ca, and Zn were directly correlated with the treatment duration with Pearson Correlation Coefficient (R) of 0.356 (Mg), 0.329 (Ca), and 0.313 (Zn), respectively (P < 0.05). On the other hand, the levels of Al and As in the 24-h urine were lower than those of the controls (P < 0.05) and were negatively correlated with the treatment time with R of -0.337 (Al) and -0.398 (As), respectively, (P < 0.05). Thus, this study indicates that the levels of metal elements may be altered in patients with Wilson disease under the treatment of D-penicillamine. PMID- 22076733 TI - Effects of added CeCl3 on resistance of fifth-instar larvae of silkworm to Bombyx mori nucleopolyhedrovirus infection. AB - One of the most important agents causing lethal disease in the silkworm is the Bombyx mori nucleopolyhedrovirus (BmNPV), while low-dose rare earths are demonstrated to increase immune capacity in animals. However, very little is known about the effects of added CeCl(3) on decreasing BmNPV infection of silkworm. The present study investigated the effects of added CeCl(3) to an artificial diet on resistance of fifth-instar larvae of silkworm to BmNPV infection. Our findings indicated that added CeCl(3) significantly decreased inhibition of growth and mortality of fifth-instar larvae caused by BmNPV infection. Furthermore, the added CeCl(3) obviously decreased lipid peroxidation level and accumulation of reactive oxygen species such as O(2)(-), H(2)O(2), (.)OH, and NO and increased activities of the antioxidant enzymes including superoxide dismutase, catalase, ascorbate peroxidase, glutathione peroxidase, ascorbate, and glutathione contents in the BmNPV-infected fifth-instar larvae. In addition, the added CeCl(3) could significantly promote acetylcholine esterase activity and attenuate the activity of inducible nitric oxide synthase in the BmNPV-infected fifth-instar larvae. These findings suggested that added CeCl(3) may relieve oxidative damage and neurotoxicity of silkworm caused by BmNPV infection via increasing antioxidant capacity and acetylcholine esterase activity. PMID- 22076734 TI - Cadmium stimulates the osteoclastic differentiation of RAW264.7 cells in presence of osteoblasts. AB - Low level of cadmium exposure may have direct effects on bone. But the probable mechanism is far from clarified. Using a co-culture system, the present study investigated the effects of low level of cadmium exposure on osteoclast differentiation in the presence of osteoblasts. Primary osteoblasts were isolated from calvarial bone of newborn Sprague Dawley rats. Primary osteoblasts and RAW264.7 cells were exposed to cadmium (0-60 nmol/l) in a co-culture system. Then, osteoblast viability was observed by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Osteoclast formation and tartrate-resistant acid phosphatase 5b levels were determined by tartrate-resistant acid phosphatase staining and enzyme-linked immunosorbent assay. Osteoprotegerin and receptor activator of NF-kB ligand mRNA expression in osteoblasts were studied via reverse transcription polymerase chain reaction. Viability of osteoblast was obviously decreased by Cd exposure (P < 0.05). Cadmium significantly stimulated the formation of osteoclasts in co-culture system (7.5-60 nmol/l) compared with the control. The levels of tartrate-resistant acid phosphatase 5b in RAW264.7 cells co-cultured with osteoblasts were significantly enhanced by cadmium exposure compared with that without cadmium. The mRNA expression of receptor activator of NF-kB ligand was upregulated by cadmium at 15 and 60 nmol/l. But cadmium had no obvious influence on osteoprotegerin mRNA expression. This data suggested that osteoblasts might be involved in the progress of cadmium effects on osteoclasts. PMID- 22076735 TI - Robotic thyroid surgery: our experience with the infraclavicular approach. AB - BACKGROUND: Robot-assisted endoscopic transaxillary thyroidectomy is an emerging surgical technique. Despite promising results it presents some limitations and remains controversial in terms of usefulness and validity. We developed an alternative robotic technique using a gasless infraclavicular approach. METHODS: We tested this approach using cadaveric dissection, then we performed the technique on a series of 21 patients from October 2009 to July 2010. RESULTS: Sixteen patients underwent total thyroidectomy and 5 patients underwent lobectomies. Mean total operative time was 197 minutes. We observed postoperative complications in 4 patients. Pathologic diagnoses included: benign follicular adenoma (19 patients) and single papillary carcinoma <1 cm in diameter pT1a (2 patients). CONCLUSIONS: The infraclavicular approach for robotic thyroidectomy is feasible, but is not safe enough to be recommended, based on our experience and on the technical difficulties encountered. The use of 2 robotic arms instead of 3 is a major limitation for this technique. PMID- 22076736 TI - Molecular characterization of boscalid- and penthiopyrad-resistant isolates of Didymella bryoniae and assessment of their sensitivity to fluopyram. AB - BACKGROUND: Didymella bryoniae has a history of developing resistance to single site fungicides. A recent example is with the succinate-dehydrogenase-inhibiting fungicide (SDHI) boscalid. In laboratory assays, out of 103 isolates of this fungus, 82 and seven were found to be very highly resistant (B(VHR) ) and highly resistant (B(HR) ) to boscalid respectively. Cross-resistance studies with the new SDHI penthiopyrad showed that the B(VHR) isolates were only highly resistant to penthiopyrad (B(VHR) -P(HR) ), while the B(HR) isolates appeared sensitive to penthiopyrad (B(HR) -P(S) ). In this study, the molecular mechanism of resistance in these two phenotypes (B(VHR) -P(HR) and B(HR) -P(S) ) was elucidated, and their sensitivity to the new SDHI fluopyram was assessed. RESULTS: A 456 bp cDNA amplified fragment of the succinate dehydrogenase iron sulfur gene (DbSDHB) was initially cloned and sequenced from two sensitive (B(S) -P(S) ), two B(VHR) P(HR) and one B(HR) -P(S) isolate of D. bryoniae. Comparative analysis of the DbSDHB protein revealed that a highly conserved histidine residue involved in the binding of SDHIs and present in wild-type isolates was replaced by tyrosine (H277Y) or arginine (H277R) in the B(VHR) -P(HR) and B(HR) -P(S) variants respectively. Further examination of the role and extent of these alterations showed that the H/Y and H/R substitutions were present in the remaining B(VHR) P(HR) and B(HR) -P(S) variants respectively. Analysis of the sensitivity to fluopyram of representative isolates showed that both SDHB mutants were sensitive to this fungicide as the wild-type isolates. CONCLUSION: The genotype-specific cross-resistance relationships between the SDHIs boscalid and penthiopyrad and the lack of cross-resistance between these fungicides and fluopyram should be taken into account when selecting SDHIs for gummy stem blight management. PMID- 22076737 TI - Group 4 dimethylsilylenebisamido complexes bearing the 6-[2 (diethylboryl)phenyl]pyrid-2-yl motif: synthesis and use in tandem ring-opening metathesis/vinyl-insertion copolymerization of cyclic olefins with ethylene. AB - Two novel Zr(IV)- and Hf(IV)-based bisamido complexes bearing the 6-[2 (diethylboryl)phenyl]pyrid-2-yl motif, that is, [ZrCl(2){Me(2)Si(DbppN)(2)}(thf)] (9) and [HfCl(2){Me(2)Si(DbppN)(2)}(thf)(2)] (10) (DbppN=6-[2 (diethylboryl)phenyl]pyridine-2-amido) have been prepared. Their reactivities have been compared with that of a model precatalyst that does not bear the aminoborane motif. Upon activation with methylalumoxane, precatalysts 9 and 10 are active in the homopolymerization of ethylene (E) yielding high-density polyethylene (HDPE). In the copolymerization of E with cyclopentene (CPE), for example by the action of 9, the presence of CPE resulted in a dramatic increase in the polymerization activity of E, while CPE incorporation remained close to or at zero. In the vinyl-insertion copolymerization of norborn-2-ene (NBE) with E by the action of 9, statistical cyclic olefin copolymers of these two monomers were obtained. At higher NBE concentrations, however, 9 gave rise to reversible ring opening metathesis (ROMP)/vinyl-insertion polymerization (VIP) of NBE with E, resulting in the formation of multi-block copolymers of the general formula poly(NBE)(ROMP)-co-poly(NBE)(VIP)-co-poly(E). This particular feature of precatalyst 9, that is, the ability to induce a reversible alpha-H elimination/alpha-H addition reaction, is attributed to the unique role of the 6 [2-(diethylboryl)phenyl]pyrid-2-yl ligand. Accordingly, a model precatalyst lacking this ligand does not have the ability to induce alpha-H elimination/alpha H addition reactions. The different (11)B NMR shifts of various diethylborylphenylpyrid-2-ylamines and -amides permit a ranking of the strengths of the B-N bonds in these compounds. This strength of the B-N bond is correlated with the propensity of 9/MAO to produce poly(NBE)(ROMP)-co-poly(NBE)(VIP)-co poly(E) at different temperatures. PMID- 22076738 TI - Gold-catalyzed intermolecular [4+2] and [2+2+2] cycloadditions of ynamides with alkenes. PMID- 22076739 TI - A multifunctional nanocarrier based on nanogated mesoporous silica for enhanced tumor-specific uptake and intracellular delivery. AB - A multifunctional drug delivery system based on MCM-41-type mesoporous silica nanoparticles is described that behaves as if nanogates were covalently attached to the outlets of the mesopores through a highly acid-sensitive benzoic-imine linker. Tumor-specific uptake and intracellular delivery results from the pH dependent progressive hydrolysis of the benzoic-imine linkage that starts at tumor extracellular pH = 6.8 and increases with decreasing pH. The cleavage of the benzoic-imine bond leads to the removal of the polypseudorotaxane caps and subsequent release of the payload drugs at tumor sites. At the same time, the carrier surface becomes positively charged, which further facilitates cellular uptake of the nanocarriers, thus offering a tremendous potential for targeted tumor therapy. PMID- 22076741 TI - Mercury and carbon dioxide emissions: uncoupling a toxic relationship. PMID- 22076742 TI - Target recycling amplification for sensitive and label-free impedimetric genosensing based on hairpin DNA and graphene/Au nanocomposites. AB - The presence of exonuclease III leads to direct recycling and reuse of the target DNA, which in turn results in substantial signal amplification for highly sensitive, label-free impedimetric detection of specific DNA sequences. PMID- 22076743 TI - [Phacolysis after blunt trauma]. PMID- 22076744 TI - Stable fluorophosphines: predicted and realized ligands for catalysis. PMID- 22076745 TI - Economical challenges to microbial producers of butanol: feedstock, butanol ratio and titer. AB - Butanol is an important solvent and transport fuel additive, and can be produced by microbial fermentation. Attempts to generate a superior microbial producer of butanol have been made through different metabolic engineering strategies. However, to date, butanol bio-production is still not economically competitive compared to petrochemical-derived production because of its major drawbacks, such as, high cost of the feedstocks, low butanol concentration in the fermentation broth and the co-production of low-value by-products acetone and ethanol. Here we analyze the main bottlenecks in microbial butanol production and summarize relevant advances from recently reported studies. Further needs and directions for developing real industrially applicable strains in butanol production are also discussed. PMID- 22076747 TI - Experimental comparison of aerial larvicides and habitat modification for controlling disease-carrying Aedes vigilax mosquitoes. AB - BACKGROUND: Microbial and insect-growth-regulator larvicides dominate current vector control programmes because they reduce larval abundance and are relatively environmentally benign. However, their short persistence makes them expensive, and environmental manipulation of larval habitat might be an alternative control measure. Aedes vigilax is a major vector species in northern Australia. A field experiment was implemented in Darwin, Australia, to test the hypotheses that (1) aerial microbial larvicide application effectively decreases Ae. vigilax larval presence, and therefore adult emergence, and (2) environmental manipulation is an effective alternative control measure. Generalised linear and mixed-effects modelling and information-theoretic comparisons were used to test these hypotheses. RESULTS: It is shown that the current aerial larvicide application campaign is effective at suppressing the emergence of Ae. vigilax, whereas vegetation removal is not as effective in this context. In addition, the results indicate that current larval sampling procedures are inadequate for quantifying larval abundance or adult emergence. CONCLUSIONS: This field-based comparison has shown that the existing larviciding campaign is more effective than a simple environmental management strategy for mosquito control. It has also identified an important knowledge gap in the use of larval sampling to evaluate the effectiveness of vector control strategies. PMID- 22076748 TI - Joint loading decreased by inexpensive and minimalist footwear in elderly women with knee osteoarthritis during stair descent. AB - OBJECTIVE: Previous studies indicate that flexible footwear, which mimics the biomechanics of walking barefoot, results in decreased knee loads in patients with knee osteoarthritis (OA) during walking. However, the effect of flexible footwear on other activities of daily living, such as descending stairs, remains unclear. Our objective was to evaluate the influence of inexpensive and minimalist footwear (Moleca) on knee adduction moment (KAM) during stair descent of elderly women with and without knee OA. METHODS: Thirty-four elderly women were equally divided into an OA group and a control group (CG). Stair descent was evaluated in barefoot condition, while wearing the Moleca, and while wearing heeled shoes. Kinematics and ground reaction forces were measured to calculate KAM by using inverse dynamics. RESULTS: The OA group experienced a higher KAM during midstance under the barefoot condition (233.3%; P = 0.028), the Moleca (379.2%; P = 0.004), and heeled shoes (217.6%; P = 0.007). The OA group had a similar knee load during early, mid, and late stance with the Moleca compared with the barefoot condition. Heeled shoes increased the knee loads during the early-stance (versus barefoot [16.7%; P < 0.001] and versus the Moleca [15.5%; P < 0.001]), midstance (versus barefoot [8.6%; P = 0.014] and versus the Moleca [9.5%; P = 0.010]), and late-stance phase (versus barefoot [10.6%; P = 0.003] and versus the Moleca [9.2%; P < 0.001]). In the CG, the Moleca produced a knee load similar to the barefoot condition only during the early-stance phase. CONCLUSION: Besides the general foot protection, the inexpensive and minimalist footwear contributes to decreasing knee loads in elderly women with OA during stair descent. The loads are similar to the barefoot condition and effectively decreased when compared with heeled shoes. PMID- 22076749 TI - Recurrent laryngeal nerve landmarks revisited. AB - BACKGROUND: The aim of this work was to evaluate, to prove their reliability, the different surgical landmarks previously proposed as a mean to locate the recurrent laryngeal nerve (RLN). METHODS: The necks of 143 (68 male and 76 female) human adult embalmed cadavers were examined. RLN origin and length and its relationship to different landmarks were recorded and results compared with those previously reported. Statistical comparisons were performed using the chi square test (significance, p <= .05). RESULTS: Mostly, RLN is located anterior to the tracheoesophageal sulcus (41.6%), posterior to the inferior thyroid artery (35.8%), lateral to Berry's ligament (88.1%), below the inferior rim of the inferior constrictor muscle (90.4%), and entering the larynx before its terminal division (54.6%). CONCLUSIONS: The position of the RLN in relation to those structures classically considered as landmarks is highly variable. The most reliable relationships are those with Berry's ligament or the inferior constrictor muscle. PMID- 22076750 TI - Detection of erythrocytes in patient with iron deficiency anemia using atomic force microscopy. AB - PURPOSE: Iron deficiency anemia (IDA) disturbs the morphology and function of erythrocytes at molecular level. The purpose of this study was to show that pathophysiological changes to erythrocytes could be detected at the nanometer scale, which is important for the early diagnosis and effective therapies of the anemia. METHODS: Blood samples were taken from six healthy volunteers and six patients with IDA before and after therapy. Changes in the morphological and biomechanical properties of erythrocytes were studied at the nanometer level using atomic force microscopy (AFM). RESULTS: There were dramatic overall shape and surface membrane deformations of the erythrocytes associated with pre- and post-therapeutic IDA compared with healthy erythrocytes. Healthy and pathological erythrocytes of IDA could be distinguished by the morphologic parameters of width, length, the ratio of length to width, valley, peak, valley-to-peak, standard deviations, and surface fluctuation. Treatment effectiveness also could be evaluated by these parameters. CONCLUSIONS: AFM is a good tool for IDA study. Erythrocyte morphology is an important determinant for diagnosing and evaluating therapeutic effect of IDA disease. PMID- 22076751 TI - Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: a randomized, controlled trial. AB - OBJECTIVES: We investigated the effects of short-term use of atorvastatin on CD34+/VEGF-R2+/CD133+/CD45- endothelial progenitor cell (EPC) count after on-pump coronary artery bypass surgery (CABG). METHODS: Between Feb-2010 and May-2010, we randomly assigned, in a placebo-controlled, double-blind study, 60 consecutive patients who underwent isolated, first-time CABG to receive either 14-day atorvastatin (40 mg/day) or placebo preoperatively. Urgent CABG and recent myocardial infarction were excluded. EPCs were quantified (cells/MUl) by flow cytometric phenotyping obtained from venous blood samples collected preoperatively (T(1)), 6-hours (T(2)), and on the 5th day postoperatively (T(3)). Levels of markers of inflammation and serum cardiac troponin I were also measured preoperatively and daily until day-5 after surgery. RESULTS: There were no differences in baseline risk factors including cholesterol profiles, and EuroSCORES between the groups. The composite primary end-point, favored statin group with higher amount of circulating, early EPC count (cells/MUl) at all time points compared with placebo (T(1), 2.30+/-0.02 versus 1.58+/-0.03, p<0.001; T(2), 5.00+/-0.06 versus 2.19+/-0.06, p<0.001; T(3), 3.03+/-0.08 versus 1.78+/ 0.02, p<0.001). Postoperative hsCRP rise were inversely correlated with EPC count, and were significantly lower in the statin group (T(1), 0.8 +/- 0.1 versus 2.2+/-1.5, p<0.001; T(2), 72.9+/-3.2 versus 96.0+/-3.6, p<0.001; T(3), 4.3+/-1.2 versus 11.4+/-4.1, p<0.001). Furthermore, the incidence of postoperative atrial fibrillation was significantly lower in the statin group compared to placebo (3.3% versus 23%, p=0.02). CONCLUSIONS: Short-term atorvastatin use increases circulating early EPCs both pre- and post-operatively and is associated with better preservation of sinus rhythm and reduced hsCRP levels. (ClinicalTrials.gov number, NCT01096875). PMID- 22076753 TI - Peering from the shadows: stem cell research and the quest for regulation in Argentina. PMID- 22076752 TI - Differentiation and transplantation of human induced pluripotent stem cell derived hepatocyte-like cells. AB - The generation of human induced pluripotent stem cells (hiPSCs) with a high differentiation potential provided a new source for hepatocyte generation not only for drug discovery and in vitro disease models, but also for cell replacement therapy. However, the reported hiPSC-derived hepatocyte-like cells (HLCs) were not well characterized and their transplantation, as the most promising clue of cell function was not reported. Here, we performed a growth factor-mediated differentiation of functional HLCs from hiPSCs and evaluated their potential for recovery of a carbon tetrachloride (CCl4)-injured mouse liver following transplantation. The hiPSC-derived hepatic lineage cells expressed hepatocyte-specific markers, showed glycogen and lipid storage activity, secretion of albumin (ALB), alpha-fetoprotein (AFP), urea, and CYP450 metabolic activity in addition to low-density lipoprotein (LDL) and indocyanin green (ICG) uptake. Similar results were observed with human embryonic stem cell (hESC) derived HLCs. The transplantation of hiPSC-HLCs into a CCl4-injured liver showed incorporation of the hiPSC-HLCs into the mouse liver which resulted in a significant enhancement in total serum ALB after 1 week. A reduction of total serum LDH and bilirubin was seen when compared with the control and sham groups 1 and 5 weeks post-transplantation. Additionally, we detected human serum ALB and ALB-positive transplanted cells in both the host serum and livers, respectively, which showed functional integration of transplanted cells within the mouse livers. Therefore, our results have opened up a proof of concept that functional HLCs can be generated from hiPSCs, thus improving the general condition of a CCl4 injured mouse liver after their transplantation. These results may bring new insights in the clinical applications of hiPSCs once safety issues are overcome. PMID- 22076754 TI - Different rearrangement behaviour of the cation or anion derived from the Diels Alder adduct of 9-ferrocenylanthracene and 1,4-benzoquinone: ring-opening or paddlewheel formation. AB - Prototropic rearrangement of the Diels-Alder adduct (3a) of 9 ferrocenylanthracene and 1,4-benzoquinone potentially furnishes 9-ferrocenyl-1,4 dihydroxytriptycene (3b) incorporating a C(2v) symmetrical paddlewheel moiety. However, reaction of 3a with HBF(4) unexpectedly yields instead 9-ferrocenyl-10 (2,5-dihydroxyphenyl)anthracene (4) via cleavage of the C9-C12 bond to generate initially a ferrocenyl-stabilized cation. Treatment of 3a with sodium hydride and iodomethane yields 1,4-dimethoxy-9-ferrocenyltriptycene (3c) in high yield but, surprisingly, also leads to fission of the C9-C12 bond resulting, after methylation, in the formation of 9-hydroxy-9-ferrocenyl-10-(2-hydroxy-5 methoxyphenyl)dihydroanthracene (12), which readily dehydrates on silica to form 9-ferrocenyl-10-(2-hydroxy-5-methoxyphenyl)anthracene (8). The X-ray crystal structures of 3a, 3c and 4 are reported. PMID- 22076755 TI - Enriching modern pharmacotherapy through synergy assessment for the combination of natural products and synthetic drugs. AB - 5-O-methylglovanon (5-O-MG) is a bioactive compound first isolated and characterized from Glycosmis plants. In this issue, Zhou et al. evaluated the anti-staphylococcal effects of 5-O-MG against ampicillin-resistant isolates of Staphylococcus aureus and S. epidermidis. The authors showed that the combination of 5-O-MG and ampicillin significantly increased the susceptibility of Staphylococcus strains to the drugs by decreasing MICs with a comparable anti staphylococcal effect to that of beta-lactamase inhibitors, suggesting that herbal compounds such as 5-O-MG may be potential candidates for the inhibitor of beta-lactamases. This study is another example of synergy assessment of natural products in drug development to likely enrich modern pharmacotherapy. PMID- 22076756 TI - A novel approach to cancer therapy using PX-478 as a HIF-1alpha inhibitor. AB - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor produced by tumor cells under hypoxic conditions, and a key regulator of a number of genes important in cancer biology. Over-expression of HIF-1alpha in human tumors is associated with poor prognosis and poor therapeutic outcomes and HIF-1alpha has been suggested as a novel target for cancer therapy. This article provides a review of PX-478 as the first novel HIF-1alpha inhibitor in clinical stage for the treatment of solid tumors. PMID- 22076757 TI - A new furostanol saponin from Asparagus cochinchinensis. AB - A new furostanol saponin, (25S)-26-O-beta-D-glucopyranosyl-5beta-furost-20(22)-en 3beta, 15beta,26-triol-3-O-[alpha-L-rhamnopyranosyl-(1-4)]-beta-D: glucopyranoside, namely, aspacochioside D (1) were isolated from Asparagus cochinchinensis (Lour.) Merr, along with three known saponins, aspacochioside C (2), (25S)-5beta-spirostan-3beta-yl-O-[O-alpha-L-rhamnopyranosyl-(1-4)]-beta-D glucopyranoside (3), and pseudoprotoneodioscin (4). The structure of 1 was elucidated on the basis of chemical reactions and spectral analysis (IR, GC, ESI MS, (1)H-NMR, (13)C-NMR, DEPT, HMBC, HMQC and NOESY). The antiproliferative effects of 1-4 were evaluated in a cytotoxicity assay against the human tumor cell line, A549. Compound 2 (Aspacochioside C) exhibited moderate cytotoxicity against A-549, with an IC(50) value of 3.87 MUg/mL. PMID- 22076758 TI - Anti-inflammatory activity on LPS-stimulated dendritic cells of lupanetype triterpenoids from the leaves of Acanthopanax koreanum. AB - Acanthopanax koreanum is well known herb in traditional Korean, Chinese, and Japanese anti-inflammatory action without any adverse effects. In the current study, we investigated the inhibitory effects of isolated compounds 1-13 from the leaves of A. koreanum on the lipopolysaccharide-stimulated production of pro inflammatory cytokines in bone marrow-derived dendritic cells. Of these lupane type triterpenoids, 1 exhibited particularly high inhibitory effect on lipopolysaccharide-stimulated TNF-alpha, IL-6, and IL-12 production with the values ranging from 45.0 to 84.5% at a concentration of 50 MUM. These results warrant further studies concerning the potential anti-inflammatory benefits of medicinal foods containing the leaves of A. koreanum. PMID- 22076759 TI - Isolation of phytosterols and antihyperlipidemic activity of Lagenaria siceraria. AB - Lagenaria siceraria (Molina) Standl in the Cucurbitaceae family is a large, pubescent, climbing, or trailing herb cultivated throughout India and the tropical regions of the world. Phytochemical investigation of the methanol extract obtained from the fruits of the plant L. siceraria showed a positive Liebermann-Burchard test for sterols. The white sterol crystals or phytosterols from the methanol extract were isolated for the first time and identified as a mixture of four sterols, including fucosterol (1), racemosol (2), stigmasterol (3), and stigmasta-7,22-dien-3beta,4beta-diol (4). These compounds were identified by spectroscopic evidence including FTIR, (1)H-NMR, MS, and GC. The white sterol crystals, which are the mixture of four sterols, were evaluated for antihyperlipidemic activity in Wistar rats. The blood samples were collected from the retro-orbital plexus and serum was separated and analyzed for lipid profiles. These sterol crystals (30 mg/kg) showed significant reductions in lipid profiles which included cholesterol, triglycerides, LDL and VLDL. In addition, a significant increase in HDL cholesterol observed, which is a good cholesterol that protects hearts from coronary artery diseases. These sterol crystals or phytosterols can be used as an antihyperlipidemic agent to treat the hyperlipidemic. PMID- 22076760 TI - Synthesis of novel quinoxalinone derivatives by conventional and microwave methods and assessing their biological activity. AB - In this study, twenty-one arylaminoquinoxalinone derivatives were synthesized and their antibacterial activities against Staphylococci aureus, Pseudomonas aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, and Shigella pneumoniae were evaluated relative to known antibiotics; augmentin, ampicillin, and chloramphenicol. The insecticidal activities of the prepared compounds were also investigated against Tribolium castaneum using permethrin as a standard insecticide. The derivatives were synthesized using both conventional and microwave techniques. Their structures were confirmed using spectral techniques and elemental analysis. PMID- 22076761 TI - Synthesis of novel isatin-thiazoline and isatin-benzimidazole conjugates as anti breast cancer agents. AB - A series of new isatin-thiazoline 3a-h and isatin-benzimidazole 4a-h derivatives were synthesized via condensation of isatin Mannich bases 2a-h with either 2 aminothiazoline or 2-aminobenzimidazole. The structures of the newly synthesized compounds were characterized by spectral data. The anti-breast cancer activity of some of the synthesized compounds was assessed in the MCF-7 human breast cancer cell line. The results showed that compounds 4b, 4d and 4g possess significant antiproliferative activity against MCF-7 cells. PMID- 22076762 TI - DNA binding, antiviral activities and cytotoxicity of new furochromone and benzofuran derivatives. AB - Bromination of visnagin (1) afforded 9-bromovisnagin (2) which on its alkaline hydrolysis afforded the 3-acetyl benzofuran derivative (3). The condensation of (3) with hydrazine hydrate, phenylhydrazine and/or hydroxylamine hydrochloride afforded the corresponding pyrazole derivatives (4a, b) and isoxazole derivative (4c). On the other hand, when compound 3 was condensed with some aromatic aldehydes, this yielded corresponding alpha, beta-unsaturated keto derivatives (5a-e). Furthermore, when 1 was subjected to chlorosulfonation, the visnaginsulfonylchloride derivative 6 was afforded, which on amidation using morpholine, a sulonamido derivative (7) was obtained. Alkaline hydrolysis of the latter compound yielded 7-N-morpholinosulsamidobenzofuran (8) which was condensed with some aromatic aldehydes to yield the corresponding chalcone compounds (9a e). Demethylation of visnagin afforded norvisnagin (10). The reaction of 10 with ethylbromoacetate in dry acetone yielded the ester benzopyran derivative (11) which reacted with hydrazine hydrate to afford the corresponding hydrazide derivative (12) and this was condensed with 3,4,5-trimethoxybenzaldehyde to give the corresponding hydrazone (13). A thaizolidinone derivative (14) was obtained by condensation of (13) with thioglycolic acid. Chloromethylation of norvisnagin afforded a 4-chloromethyl derivative (15) which reacted with different primary and secondary amines to yield the corresponding ethylamino derivative (16a, b). Moreover, mannich bases (16a, b) and (17a-c) were obtained by reacting norvisnagin with different primary and secondary amines in the presence of formalin but benzoylation of (16a, b) and (17a-c) afforded 4-oxybenzoyl derivative (18a-e). The prepared compounds were tested for their interaction with DNA; bromovisnagin 2 showed the highest affinity and compounds 6, 15, 8a, > 14, > 16b, 17a, and 16a showed moderate activity in decreasing potency. Moreover, compound 2 also was the most active as antiviral agent toward HS-I virus and compounds 6, 7, 15, 14, 16a, and 18a were found to be moderately active. CD(50) of the active compounds were also measured. PMID- 22076763 TI - A beta-resorcylic macrolide from the seagrass-derived fungus Fusarium sp. PSU ES73. AB - A new beta-resorcylic macrolide, 5'-hydroxyzearalenone (1), and six known beta resorcylic macrolides were isolated from the seagrass-derived fungus Fusarium sp. PSU-ES73. Their structures were established by analysis of spectral data. All of the isolated compounds were evaluated for their antibacterial activity against Staphylococcus aureus, both standard and methicillin-resistant strains, as well as their antifungal activity against Cryptococcus neoformans. Only the known compound zearalenone (2) displayed weak antibacterial and antifungal activities. PMID- 22076764 TI - Synthesis of novel 4-(1H-benzimidazol-2-yl)benzene-1,3-diols and their cytotoxic activity against human cancer cell lines. AB - One-pot synthesis of new biologically active 4-(1H-benzimidazol-2-yl)benzene-l,3 diols has been developed. The compounds were prepared by the reaction of aryl modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]s with benzene-l,2 diamines. Their structures were identified using elemental, IR, (1)H-NMR, and mass spectra analyses. The developed method offers short reaction times, relatively large-scale synthesis, easy and quick isolation of the products, and good yields. The cytotoxicity in vitro against the 4 human cancer cell lines: SW707 (rectal), HCV29T (bladder), A549 (lung), and T47D (breast) was determined. The antiproliferative properties of some compounds studies were stronger than those of cisplatin, which was used as a comparator drug. PMID- 22076765 TI - Synthesis and antifungal activity of novel triazole derivatives. AB - A series of novel azoles (a-v), which are analogues of fluconazole, have been designed and synthesized as potential antifungal agents by the click reaction. The click reaction approach toward the synthesis of novel 1,2,3-triazolyl linked triazole antifungal derivatives a-v was achieved by Cu(I)-catalyzed 1,3-dipolar cycloaddition of propargylated intermediate 5 with substituted azidomethyl benzene. In addition, the target compounds tested can increase antifungal activity. PMID- 22076766 TI - Effects of vegetative and flowering stages on the biosynthesis of artemisinin in Artemisia species. AB - Artemisinin is an endoperoxide sesquiterpene lactone, and has been proven to be very effective in treating drug resistant cases of malaria, cancer, etc. The compound is obtained from Artemisia species. In the current study, the effects of vegetative and flowering stages on artemisinin production were studied, to determine the proper harvesting time of naturally growing Artemisia species with the highest levels of artemisinin. Eight Artemisia species along with two varieties were selected for this analytical work. The results showed that artemisinin content was high in the leaves of Artemisia indica, A. sieversiana, A. roxburghiana var. roxburghiana, A. roxburghiana var. gratae, and A. parviflora at the flowering stage. The highest artemisinin content was measured in the leaves of A. dracunculus var. dracunculus. Upon comparisons of artemisinin content among the individual plant species, the highest amount of artemisinin was again in A. dracunculus var. dracunculus followed by A. sieversiana when harvested at the flowering stage. In overall comparisons, the plants at the flowering stage showed high levels of artemisinin, which is deemed the optimum harvesting time of Artemisia species in Pakistan for maximum artemisinin content. PMID- 22076767 TI - Moxifloxacin-Gelrite in situ ophthalmic gelling system against photodynamic therapy for treatment of bacterial corneal inflammation. AB - In this study, six in situ gelling formulations based on Gelrite were prepared and evaluated for the retained ophthalmic delivery of Moxifloxacin (Mox). The effectiveness of the best developed formula G5 was compared with photodynamic therapy (PDT), the recent expanding approach for the treatment of ophthalmologic disorders after the assessment of optimum photodynamic inactivation parameters that permit efficient pathogens eradication. It was found that, Staphylococcus aureus (S. aureus) (Gram-positive) was more susceptible to effective lethal photosensitization that reaches 93.5% reduction in viable count than Escherichia coli (E. coli) (Gramnegative) of 76.1% using 3 mg/mL Hematoporphyrin (HP), illuminated by 630 nm Light Emitting Diode (LED) at 9 J/cm(2) and incubated for 15 min. Following topical instillation of G5 to rabbits corneas, higher amount of Mox was retained in the aqueous humor up to 24 h with significant 6-fold increase in the C(max) and AUC((0-infinity)) compared to vigamox commercial eye drops. After post corneal infection with S. aureus, both approaches were effectively treating the infection without causing ocular irritation or collateral damage to corneal tissue where G5 showed remarkable improvement after four days compared to seven days of PDT treatment. PMID- 22076768 TI - Anti-P-glycoprotein conjugated nanoparticles for targeting drug delivery in cancer treatment. AB - Targeting therapeutics to specific sites can enhance the efficacy of drugs, reduce required doses as well as unwanted side effects. In this work, using the advantages of the specific affinity of an immobilized antibody to membrane P-gp in two different nanoparticle formulations were thus developed for targeted drug delivery to multi-drug resistant cervical carcinoma (KB-V1) cells. Further, this was compared to the human drug sensitive cervical carcinoma cell line (KB-3-1) cells. The two nanoparticle preparations were: NP1, anti-P-gp conjugated with poly (DL-lactic-coglycolic acid) (PLGA) nanoparticle and polyethylene glycol (PEG); NP2, anti-P-gp conjugated to a modified poloxamer on PLGA nanoparticles. The cellular uptake capacity of nanoparticles was confirmed by fluorescent microscopy. Comparing with each counterpart core particles, there was a higher fluorescence intensity of the targeted nanoparticles in KBV1 cells compared to KB 3-1 cells suggesting that the targeted nanoparticles were internalized into KB-V1 cells to a greater extent than KB-3-1 cell. The results had confirmed the specificity and the potential of the developed targeted delivery system for overcoming multi-drug resistance induced by overexpression of P-gp on the cell membrane. PMID- 22076769 TI - Formulation, development, and performance evaluation of metoclopramide HCl oro dispersible sustained release tablet. AB - The present study was undertaken to develop and evaluate an oro-dispersible, sustained release tablet of metoclopramide HCl. The technology was comprised of developing sustained release microparticles, and compression of resultant microspheres into a fast dispersible tablet by direct compression. The microspheres of metoclopramide HCl were prepared by an emulsification-solvent evaporation method using ethylcellulose as the matrix polymer. The prepared microspheres were evaluated for morphology, particle size, entrapment efficiency, and in vitro drug release characteristics. Scanning electron microscopy demonstrated spherical particles with a mean diameter of 81.27 +/- 5.87 MUm and the drug encapsulation efficiency was found to be 70.15 +/- 3.06%. The process and formulation variables such as rotation speed, polymer concentration, and drug concentration influenced the drug encapsulation efficiency and in vitro drug release. Optimized microspheres were compressed into tablets which were comprised of metoclopramide HCl microspheres, 53% (w/v) of D-mannitol granules, 7% (w/w) of Polyplasdone XL 10, and 0.5% (w/w) of calcium stearate. The tablets demonstrated a hardness of 59 +/- 3 N, friability of 0.21% and disintegration time of 27 +/- 3 sec. The formulations were subjected to stability studies as per ICH guidelines and were found to be stable after a 6 month study. In vivo experiments conducted in rats demonstrated that a constant level of metoclopramide HCl in plasma could be maintained for up to 20 h at a suitable concentration for antiemetic activity. An appropriate combination of excipients made it possible to obtain orally disintegrating sustained release tablets of metoclopramide HCl using simple and conventional techniques. PMID- 22076770 TI - Transmucosal delivery of domperidone from bilayered buccal patches: in vitro, ex vivo and in vivo characterization. AB - Bilayered mucoadhesive buccal patches for systemic administration of domperidone (DOM), a dopamine-receptor (D(2)) antagonist, were developed using hydroxy propyl methyl cellulose and PVPK30 as a primary layer and Eudragit RLPO and PEO as a secondary layer. Ex vivo drug permeation through porcine buccal membrane was performed. Bilayered buccal patches were developed by solvent casting technique and evaluated for in vitro drug release, moisture absorption, mechanical properties, surface pH, in vitro bioadhesion, in vivo residence time and ex vivo permeation of DOM through porcine buccal membrane from a bilayered buccal patch. Formulation DB4 was associated with 99.5% drug release with a higuchi model release profile and 53.9% of the drug had permeated in 6 h, with a flux of 0.492 mg/h/cm(2) through porcine buccal membrane. DB4 showed 5.58 N and 3.28 mJ peak detachment force and work of adhesion, respectively. The physicochemical interactions between DOM and the polymer were investigated by differential scanning calorimetry (DSC) and fourier transform infrared (FTIR) Spectroscopy. DSC and FTIR studies revealed no interaction between drug and polymer. Stability studies for optimized patch DB4 was carried out at 40 degrees C/75% relative humidity. The formulations were found to be stable over a period of 3 months with respect to drug content, in vitro release and ex vivo permeation through porcine buccal membrane. The results indicate that suitable bilayered mucoadhesive buccal patches with desired permeability could be prepared. PMID- 22076771 TI - Development of coated nifedipine dry elixir as a long acting oral delivery with bioavailability enhancement. AB - To develop the long acting nifedipine oral delivery with bioavailability enhancement, a nifedipine dry elixir (NDE) containing nifedipine ethanol solution in dextrin shell was prepared using a spray-dryer, and then coated nifedipine dry elixir (CNDE) was prepared by coating NDE with Eudragit acrylic resin. The physical characteristics and bioavailability of NDE and CNDE were evaluated, and then compared to those of nifedipine powder. NDE and CNDE, which were spherical in shape, had about 6.64 and 8.68-8.75 MUm of geometric mean diameters, respectively. The amount of nifedipine dissolved from NDE for 60 min increased about 7- and 40-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, respectively. Nifedipine released from CNDE was retarded in both dissolution media compared with that from NDE. After oral administration of NDE, the C(max) and AUC(0->8h) of nifedipine in rat increased about 13- and 7-fold, respectively, and the Tmax of nifedipine was reduced significantly compared with those after oral administration of nifedipine powder alone. The AUC(0->8h) and T(max) of nifedipine in CNDE increased markedly and the C(max) of nifedipine in CNDE was significantly reduced compared to those in NDE. It is concluded that CNDE, which could lower the initial burst-out plasma concentration and maintain the plasma level of nifedipine over a longer period with bioavailability enhancement, might be one of potential alternatives to the marketed long acting oral delivery system for nifedipine. PMID- 22076772 TI - Effect of pluronic P123 and F127 block copolymer on P-glycoprotein transport and CYP3A metabolism. AB - The aim of the present study was to evaluate the effect of pluronic P123 (P123) and pluronic F127 (F127) on intestinal P-glycoprotein (P-gp) and cytochrome P450 3A using the specific substrates rhodamine-123 (R-123) and midazolam, respectively. Caco-2 cells and everted gut sacs were used as models of intestinal mucosa to assess intestinal absorption of R-123, while rat intestinal microsomes were utilized to examine the effect of P123 and F127 on in vitro midazolam metabolism. P123 and F127 were observed to increase the intracellular accumulation of R-123 in Caco-2 cells in a dose-dependent manner. P123 significantly lowered the efflux ratio of R-123 at two concentrations in Caco-2 monolayers, whereas F127 lowered the efflux ratio only at 1%. Moreover, both pluronics markedly enhanced mucosal to serosal absorption of R-123 in excised ileum of rats. However, no significant difference in relative enzyme activity were observed between P123- or F127-treated and control groups, regardless of the concentrations of P123 and F127 studied. Collectively, these results obtained from the present study demonstrated that P123 and F127 were capable of inhibiting the intestinal P-gp activity, but had little or no effect on intestinal cytochrome P450 3A activity, indicating that P123 and F127 can potentially be used as pharmaceutical ingredients to improve the oral bioavailability of coadministered P-gp substrates via P-gp efflux pump inhibition. PMID- 22076773 TI - Effects of morin on the pharmacokinetics of docetaxel in rats with 7,12 dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. AB - Docetaxel is a P-glycoprotein (P-gp) substrate and metabolized via cytochrome P450 (CYP) 3A subfamily in rats. Morin is an inhibitor of both CYPs and P-gp. Hence, the effects of morin on the intravenous and oral pharmacokinetics of docetaxel were investigated using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor rats (DMBA rats) as an animal model of human breast cancer. Docetaxel was administered intravenously (4 mg/kg) and orally (20 mg/kg) without and with morin (15 mg/kg) in DMBA rats. After the intravenous administration of docetaxel in control and DMBA rats with and without morin, the values of non renal clearance and area under the plasma concentration-time (AUC) for docetaxel were comparable. Morin did not increase AUC or the absolute oral bioavailability (F) for docetaxel after the oral administration of docetaxel in control and DMBA rats with and without morin. The inhibition of hepatic and intestinal metabolism of docetaxel by morin and/or DMBA and the effect of intestinal P-gp inhibition by morin on the pharmacokinetics of docetaxel did not seem to be considerable in DMBA-induced mammary tumor rats. PMID- 22076774 TI - Gene network analysis on the effect of Viscum album var. coloratum in T cells stimulated with anti-CD3/CD28 antibodies. AB - A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. var. coloratum agglutinin, VCA), which is known for its anticancer activity, was isolated from Korean mistletoe. This study reports a microarray analysis of the effects of VCA on an activated human T cells under various times and concentrations. A total of over 3000 genes were identified whose expression levels were significantly altered against controls after treatment with VCA and anti-CD3/CD28 antibody stimulation on human T-cells over an 8 h period. An analysis of the gene expression profile induced by VCA following incubation in human T cells revealed the activation and inhibition of genes involved in a wide range of immune functions in line with the broad mechanisms of action of VCA. These functions include cytokine gene expression, cell adhesion, cell motility, cell growth and maintenance, cell death, and the response to stress and to external stimulus. This report is aimed at providing the mistletoe research community with a robust database on which further studies could be built. PMID- 22076775 TI - In vitro synergistic interaction of 5-O-methylglovanon and ampicillin against ampicillin resistant Staphylococcus aureus and Staphylococcus epidermidis isolates. AB - 5-O-methylglovanon (5-O-MG) is a bioactive compound that was first isolated and characterized from Glycosmis plants. In this study, we found that chemically synthesized 5-O-MG has antimicrobial ability against eleven clinical ampicillin resistant Staphylococcus aureus and S. epidermidis isolates. The MICs of 5-O-MG against the S. aureus and S. epidermidis isolates were 12.5-50 MUg/mL and 25-50 MUg/mL, respectively. In combination with ampicillin, a synergistic interaction between 5-O-MG and ampicillin against the eleven resistant Staphylococcus isolates was observed, with fractional inhibitory concentration indices of 0.03 0125. Moreover, the anti-staphylococcal activity of 5-O-MG in combination with ampicillin was comparable with that of clavulanic acid in combination with ampicillin. The drug combination had no antagonistic effects when tested against any of the strains. Time-killing assays confirmed the synergy between 5-O-MG and ampicillin (p < 0.01). The combination of these two agents yielded greater than a 2 log(10) cfu/mL decrease in comparison with 5-O-MG or ampicillin alone. These findings suggest that 5-O-MG is a promising compound with the potential for future anti-staphylococcal drug development. PMID- 22076776 TI - The mechanism of MAP kinase activation under acidic condition in feline esophageal smooth muscle cells. AB - Reflux esophagitis results from repeated exposure of the esophagus to acidic gastric juice or bile-containing duodenal contents. In Barrett's adenocarcinoma, acid increases proliferation via ERK and p38 MAPK activation. This study was focused on determination of the mechanism(s) underlying MAPKs (ERK 1/2, p38 MAPK, and JNK) activation induced by acidic medium at pH 4 in normal feline primary cultured esophageal smooth muscle cells (FESMCs). We detected ERK 1/2 and p38 MAPK phosphorylation after exposure to pH 4 or neutral media in the presence or absence of several inhibitors and quantified the MAPK levels using western blotting analysis and densitometry. Acidic medium markedly increased the phosphorylation of ERK 1/2 and p38 MAPK within 10 min. Acid-induced ERK 1/2 and p38 MAPK activation was inhibited by pertussis toxin (PTX-sensitive G(i/o) protein inhibitor), DEDA (phospholipase (PL) A(2) inhibitor), rhoCMB (PLD inhibitor), GF109203X (protein kinase C (PKC) inhibitor) and D609 (phosphatidylcholine-specific PLC inhibitor). But, genistein (tyrosine kinase inhibitor), forskolin (adenylate cyclase activator) and U73122 (phosphatidylinositol-specific PLC inhibitor) had no effect on acid-induced ERK1/2 and p38 MAPK activation. These findings indicate that the activation of ERK 1/2 and p38 MAPK pathways by acidic conditions, at least in part, may be mediated by activation of the G(i/o) protein coupled receptors, PC-PLC, PLD, PLA(2), and PKC in FESMCs. PMID- 22076778 TI - Influence of ramiprilat and losartan on ischemia reperfusion injury in rat hearts. AB - HYPOTHESIS/INTRODUCTION: Our aim was to investigate whether a non-hypotensive dose of ramiprilat and losartan has myocardial protective effects during myocardial ischemia/reperfusion in vivo. MATERIALS AND METHODS: Three groups of rats were given 10 mg/kg per day of losartan for one (L-1W), four (L-4W) or 10 (L 10W) weeks. Another three groups were given 50 ug/kg per day of ramiprilat for one (R-1W), four (R-4W) or 10 (R-10W) weeks. The animals underwent 30 min of left anterior descending artery occlusion and subsequent reperfusion for 120 min. RESULTS: Myocardial infarct size (IS) was reduced in R-1W (28.4 +/- 6.3%, p < 0.001), R-4W (27.8 +/- 7.4, p < 0.001), L-4W (31.8 +/- 6%, p < 0.05) and L-10W (25.3 +/- 5.7, p < 0.001) groups compared with a saline group (48.3 +/- 7.8%). A significant reduction in the number of ventricular ectopic beats (VEBs) was noted in groups R-1W (209 +/- 41, p < 0.01), R-4W (176 +/- 39, p < 0.01), L-4W (215 +/- 52, p < 0.05) and L-10W (191 +/- 61, p < 0.01 vs. saline 329 +/- 48). The incidence of irreversible ventricular fibrillation (VF) and mortality were decreased significantly only in L-10W group. There were no significant decreases in episodes of VT, the incidence of irreversible VF and mortality in all of the groups treated with ramiprilat. CONCLUSION: These data indicate that losartan and ramiprilat protect the heart against ischemia/reperfusion injury independently of their hemodynamic effects but in a time-dependent manner. PMID- 22076779 TI - Highly active Pt@Au nanoparticles encapsulated in perfluorosulfonic acid for the reduction of oxygen. AB - The Pt@Au catalysts demonstrate remarkably high oxygen reduction reaction (ORR) activity compared with Pt/C catalysts. The ORR of Pt(2)@Au(1)/C and Pt(1)@Au(2)/C is 9.5 and 6.6 times that of Pt/C, respectively. This improvement is attributed to the electronic structure effect of the Au core on the Pt shell and introduction of PFSA. PMID- 22076780 TI - [Influence of nosocomial infections on resection of tracheal stenosis after tracheotomy]. AB - BACKGROUND: Complications located at the tracheostoma often occur in combination with nosocomial infections. We posed the question: how is the surgical result in tracheal resections influenced by bacterial contamination with multiresistant germs? PATIENTS AND METHODS: Between 2005 and 2009 we performed a primary end-to end-resection of the trachea after tracheotomy in 30 patients. The demographic basic data, the diagnostic data on tracheal stenosis after decanullation and type of tracheotomy were documented. Preoperatively all patients underwent a flexible bronchoscopy with bronchial lavage. All patients received an antibiotic inhalation therapy postoperatively. RESULTS: 16 patients presented a status post permanent tracheotomy (PT), in 14 cases after percutaneous dilatative tracheotomy (PDT). In 64 % of all cases the preoperative bronchial lavage was positive for bacterial contamination. The major pathogen was with 23 % a multiresistant Pseudomonas aeruginosa (MR). In three cases long-term-complications occurred, all of which were bacterially contaminated. CONCLUSION: After long-term intubation a bacterial contamination is very common and presents a negative predictor for the outcome of primary tracheal end-to-end resections. A prophylactic postoperative antibiotic therapy can improve the short- and long-term results. PMID- 22076781 TI - [Implementing in-patient smoking cessation interventions. Basic characteristics of smoking patients in a lung health department]. AB - BACKGROUND: Hospitals have a unique key role in promoting smoking cessation. However, cessation interventions are uncommon in clinical routine despite their proven effectiveness. For planning a tailored intervention for hospitalised patients we examined the characteristics of smokers in our department for lung diseases. METHODS AND PATIENTS: From July to September 2009 we evaluated the smoking status of all admitted patients. The smoking status was validated by measuring the CO-Hb. Smokers admitted for the first time on one of our regular wards received a comprehensive questionnaire. Patients with a duration of stay of 2 days or less and patients with substantial cognitive or linguistic limitations were excluded. Clinical data was collected from the participating smokers. RESULTS: 25% of all admitted patients were smokers. The participation rate was almost 90% of the eligible smokers. Our questionnaire was very well accepted und provided multitude helpful information for a following cessation counselling. Up to 3 or 4 smokers per day should be anticipated for a cessation intervention at an 80-bed-hospital. At least one counselling contact could be enabled. Although 75% of participants had experienced at least one unsuccessful quit attempt, only a minority used any support or help for cessation so far. CONCLUSIONS: Specific questionnaires to evaluate the smoking history of patients in hospitals are very suitable and facilitate a subsequent bedside-counseling. To come up with their key role in promoting smoking cessation more hospitals as yet should implement cessation interventions. PMID- 22076782 TI - [Endoscopy of peripheral lung nodule]. AB - Pulmonary nodules of unknown dignity, often incidental findings, still present a diagnostic challenge. Next to operative resection, we find minimal invasive therapies such as transthoracal punctions and bronchoscopy with transbronchial as further options. By using modern navigation techniques, the validity of bronchoscopy in diagnosing pulmonary nodules, compared to x-ray fluoroscopy, has already been improved. Thus, the use of endobronchial ultrasound, electromagnetic navigation and virtual bronchoscopy--even without x-ray fluoroscopy--is possible and the combination augments sensitivity. These techniques already rate high in patients with unclear peripheral pulmonary nodules and high risk profiles to surgical operations, thus not to be operated, but still in need of further diagnostic procedures in order to plan therapy options. A future use of endoscopic therapies may possibly be a first approach. PMID- 22076783 TI - Multifunctional mesoporous composite nanocapsules for highly efficient MRI-guided high-intensity focused ultrasound cancer surgery. AB - Bloodless surgical knife: Nano-biotechnology has been introduced into imaging guided high-intensity focused ultrasound (HIFU) cancer surgery by adopting engineered multifunctional manganese-based mesoporous composite nanocapsules as the contrast agents for T(1)-weighted magnetic resonance imaging (MRI) and simultaneously as synergistic agents for MRI-guided HIFU cancer surgery. PMID- 22076784 TI - Increased frequency of complement C4B deficiency in rheumatoid arthritis. AB - OBJECTIVE: To assess the copy number variation of complement C4A and C4B genes in patients with rheumatoid arthritis (RA). METHODS: DNA samples were obtained from 299 patients and controls and analyzed for copy number variation of total complement C4, C4A, and C4B genes. The results were compared by chi-square analysis, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Chi-square analysis revealed similar distribution patterns of total C4 alleles in RA patients (n = 160), non-RA patients (n = 88), and healthy controls (n = 51). There was no trend toward C4A deficiency as in lupus. Significant differences in C4B distribution were observed in RA patients, in whom an ~2-fold increase in the frequency of homozygous and/or heterozygous C4B deficiency (0 or 1 allele) (40%) was present relative to non-RA patients or healthy controls (both 21.6%). C4B deficiency was more frequent in seropositive RA patients than in seronegative RA patients (44% versus 31%). The odds of C4B deficiency were 2.99 (95% CI 1.58-5.65) (P = 0.0006) in seropositive RA patients relative to non-RA controls. These findings were confirmed in a larger healthy control cohort, yielding an OR of 1.83 (95% CI 1.21-2.76) (P = 0.0056). The association of the shared epitope with C4B deficiency was significantly greater in seropositive RA patients than in non-seropositive RA controls (96% versus 54.5%) (P < 0.0001), suggesting that C4B deficiency interacts with the shared epitope in the development of seropositive RA. CONCLUSION: Our findings indicate a relationship between C4B copy number variation and RA that approximates that seen between C4A copy number variation and lupus. The concurrence of C4B deficiency and the shared epitope in seropositive RA may have broad implications for our understanding of RA pathogenesis. PMID- 22076785 TI - Phase II trial of capecitabine plus cisplatin as first-line therapy in patients with metastatic nasopharyngeal cancer. AB - BACKGROUND: Capecitabine is an oral fluoropyrimidine with single-agent activity in metastatic nasopharyngeal carcinoma (NPC). This multicenter phase II study was conducted to investigate the efficacy and safety of capecitabine plus cisplatin as a first-line treatment for metastatic NPC. METHODS: Patients with metastatic NPC received cisplatin 100 mg/m(2) day 1 plus capecitabine 1000 mg/m(2) twice daily on days 1 to 14 every 3 weeks for 6-8 cycles. The primary endpoint was overall response rate. RESULTS: Forty-four patients were enrolled; 39 patients were evaluable for efficacy. The overall response rate was 53.8% (95% confidence interval [CI], 37%-70%), including 1 complete response. Median time to tumor progression was 7.3 months (95% CI, 5.6-9.9 months) and median overall survival was 28.0 months (95% CI, 14.5 months-not reached). Common grade 3/4 adverse events were neutropenia (50%), vomiting (11%), thrombocytopenia (9%), and nausea (7%). CONCLUSIONS: Capecitabine plus cisplatin is an active first-line combination in metastatic NPC that requires a short hospital stay. PMID- 22076786 TI - Is the Nail Psoriasis Severity Index reliable in the assessment of nail psoriasis by rheumatologists? AB - OBJECTIVE: To determine the agreement and reliability of the Nail Psoriasis Severity Index (NAPSI) in the assessment of nail involvement in patients with psoriatic arthritis (PsA) when performed by rheumatologists with no experience in using this instrument. METHODS: In total, 3 women with PsA, satisfying the Classification of Psoriatic Arthritis Study Group criteria, with nail involvement were selected from an outpatient clinic devoted to PsA. The assessors consisted of 2 groups: 8 expert rheumatologists in the field of PsA who were members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and had extensive experience of >10 years, and 69 rheumatologists who had never previously used the NAPSI. A video showing the nail of each selected patient (patient A, patient B, and patient C) with the most nail PsA dystrophy was shown to these 2 groups. The 8 assessors of the first group, previously trained in using the NAPSI, evaluated the 3 videos independently by using the NAPSI score. The second group scored the NAPSI after an educational session. This evaluation was repeated after 6 hours with a different sequence of videos (unpaired fashion). Interreader and intrareader reliability were estimated by calculating intraclass correlation coefficients (ICCs) and associated 95% confidence intervals (95% CIs). RESULTS: The interreader reliability showed ICC 0.934 (95% CI 0.7504-0.9983). Intrareader reliability showed ICC 0.463 (95% CI 0.134-0.668), ICC 0.148 (95% CI 0.3767-0.4722), and ICC 0.354 (95% CI 0.0425-0.600) for patient A, patient B, and patient C, respectively. CONCLUSION: These results show that the NAPSI may be an unreliable instrument to assess nail involvement when used by untrained rheumatologists in clinical practice. PMID- 22076787 TI - Application of a classification system focusing on potential asphyxia for cases of sudden unexpected infant death. AB - Current classification schemes for sudden unexpected infant death (SUID) may not be optimal for capturing scene events that potentially predispose to asphyxia. (1) To compare causes of death in a group of SUID cases assigned by multiple reviewers using our recently published classification scheme for SUID that is based on asphyxial risk at the death scene, and (2) To compare these newly assigned causes of death to that originally assigned by the medical examiners of record who performed the autopsies. Five reviewers independently assigned causes of death for 117 cases of SUID, including 83 originally diagnosed as sudden infant death syndrome (SIDS), accessioned into the San Diego SIDS/SUDC Research Project from the San Diego County Medical Examiner's Office. The diagnostic categories are: A: SIDS; B: Unexplained-Potentially Asphyxia; C: Unexplained Other Potential Causes of Death; D: Unclassified-Other; E: Unclassified; and F: Known Cause of Death. The reviewers collectively opined that conditions at the death scene contributed to or caused death in 32-50% of all of the 117 cases as well as in 40-59% of the 83 originally diagnosed SIDS cases. Another cause of death was considered plausible in 2-12% of the SIDS cases. Application of this new classification system resulted in 55-69% decrease in SIDS diagnoses. Asphyxia as a potential contributor to, or as the specific cause of death, appears to exist in a large percentage of cases designated as SIDS using other classification schemes. When certifiers use a classification system that focuses upon potential asphyxia in determining the cause of death the incidence of SIDS dramatically declines. PMID- 22076788 TI - Sudden unexpected death in infancy (SUDI): suggested classification and applications to facilitate research activity. PMID- 22076790 TI - On the mode of action of the herbicides cinmethylin and 5-benzyloxymethyl-1, 2 isoxazolines: putative inhibitors of plant tyrosine aminotransferase. AB - BACKGROUND: The mode of action of the grass herbicides cinmethylin and 5 benzyloxymethyl-1,2-isoxazolines substituted with methylthiophene (methiozolin) or pyridine (ISO1, ISO2) was investigated. RESULTS: Physiological profiling using a series of biotests and metabolic profiling in treated duckweed (Lemna paucicostata L.) suggested a common mode of action for the herbicides. Symptoms of growth inhibition and photobleaching of new fronds in Lemna were accompanied with metabolite changes indicating an upregulation of shikimate and tyrosine metabolism, paralleled by decreased plastoquinone and carotenoid synthesis. Supplying Lemna with 10 uM of 4-hydroxyphenylpyruvate (4-HPP) reversed phytotoxic effects of cinmethylin and isoxazolines to a great extent, whereas the addition of L-tyrosine was ineffective. It was hypothesised that the herbicides block the conversion of tyrosine to 4-HPP, catalysed by tyrosine aminotransferase (TAT), in the prenylquinone pathway which provides plastoquinone, a cofactor of phytoene desaturase in carotenoid synthesis. Accordingly, enhanced resistance to ISO1 treatment was observed in Arabidopsis thaliana L. mutants, which overexpress the yeast prephenate dehydrogenase in plastids as a TAT bypass. In addition, the herbicides were able to inhibit TAT7 activity in vitro for the recombinant enzyme of A. thaliana. CONCLUSION: The results suggest that TAT7 or another TAT isoenzyme is the putative target of the herbicides. PMID- 22076791 TI - Blood exchange and malaria. PMID- 22076793 TI - FIB preparation and SEM investigations for three-dimensional analysis of cell cultures on microneedle arrays. AB - We report the investigation of the interfaces between microneedle arrays and cell cultures in patch-on-chip systems by using Focused Ion Beam (FIB) preparation and Scanning Electron Microscopy (SEM). First, FIB preparations of micro chips are made to determine the size and shape of the designed microneedles. In this essay, we investigate the cell-substrate interaction, especially the cell adhesion, and the microneedle's potential cell penetration. For this purpose, cross-sectional preparation of these hard/soft hybrid structures is performed by the FIB technology. By applying the FIB technology followed by high-resolution imaging with SEM, new insights into the cell-substrate interface can be received. One can clearly distinguish between cells that are only in contact with microneedles and cells that are penetrated by microneedles. A stack of slice images is collected by the application of the slice-and-view setup during FIB preparation and is used for three-dimensional reconstruction of cells and micro-needles. PMID- 22076792 TI - Multimodal magnetic resonance imaging: The coordinated use of multiple, mutually informative probes to understand brain structure and function. AB - Differing imaging modalities provide unique channels of information to probe differing aspects of the brain's structural or functional organization. In combination, differing modalities provide complementary and mutually informative data about tissue organization that is more than their sum. We acquired and spatially coregistered data in four MRI modalities--anatomical MRI, functional MRI, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS)- from 20 healthy adults to understand how interindividual variability in measures from one modality account for variability in measures from other modalities at each voxel of the brain. We detected significant correlations of local volumes with the magnitude of functional activation, suggesting that underlying variation in local volumes contributes to individual variability in functional activation. We also detected significant inverse correlations of NAA (a putative measure of neuronal density and viability) with volumes of white matter in the frontal cortex, with DTI-based measures of tissue organization within the superior longitudinal fasciculus, and with the magnitude of functional activation and default-mode activity during simple visual and motor tasks, indicating that substantial variance in local volumes, white matter organization, and functional activation derives from an underlying variability in the number or density of neurons in those regions. Many of these imaging measures correlated with measures of intellectual ability within differing brain tissues and differing neural systems, demonstrating that the neural determinants of intellectual capacity involve numerous and disparate features of brain tissue organization, a conclusion that could be made with confidence only when imaging the same individuals with multiple MRI modalities. PMID- 22076794 TI - Biophysical and cellular-uptake properties of mixed-sequence pyrrolidine-amide oligonucleotide mimics. AB - Previously we introduced the positively charged pyrrolidine-amide oligonucleotide mimics (POM), which possess a pyrrolidine ring and amide linkage in place of the sugar-phosphodiester backbone of natural nucleic acids. Short POM homo-oligomers have shown promising DNA and RNA recognition properties. However, to better understand the properties of POM and to assess their potential for use as modulators of gene expression and bioanalytical or diagnostic tools, more biologically relevant, longer, mixed-sequence oligomers need to be studied. In light of this, several mixed-sequence POM oligomers were synthesised, along with fluorescently labelled POM oligomers and a POM-peptide conjugate. UV thermal denaturation showed that mixed-sequence POMs hybridise to DNA and RNA with high affinity but slow rates of association and dissociation. The sequence specificity, influence of terminal amino acids, and the effect of pH and ionic strength on the DNA and RNA hybridisation properties of POM were extensively investigated. In addition, isothermal titration calorimetry (ITC) was used to investigate the thermodynamic parameters of the binding of a POM-peptide conjugate to DNA. Cellular uptake experiments have also shown that a fluorescently labelled POM oligomer is taken up into HeLa cells. These findings demonstrate that POM has the potential for use in a variety of applications, alongside other modified nucleic acids developed to date, such as peptide nucleic acids (PNA) and phosphoramidate morpholino oligomers (PMO). PMID- 22076795 TI - Pseudorotaxane structure of a fullerene derivative--cyclodextrin 1:2 complex. AB - X-Ray crystallography revealed that the C(60) derivative.gamma-cyclodextrin (gamma-CDx) complex has a pseudorotaxane structure and the structure of the crystal clarified the importance of multi-point hydrogen bonds between two gamma CDxs for stabilising the 3.gamma-CDx complex. PMID- 22076796 TI - [Investigation on the 3 D geometric accuracy and on the image quality (MTF, SNR and NPS) of volume tomography units (CT, CBCT and DVT)]. AB - PURPOSE: The study aims at investigating how far image quality (MTF and NPS) differs in between CT, CBCT and DVT units and how far the geometrical 3 D accuracy and the HU calibration differ in respect to surgical or radio therapeutic planning. MATERIALS AND METHODS: X ray image stacks have been made using a new designed test device which contains structures for measuring MTF, NPS, the 3 D accuracy and the Hounsfield calibration (jaw or skull program). The image stacks of the transversal images were analyzed with a dedicated computer program. RESULTS: The MTF values are correlated with the physical resolution (CT and DVT) and are influenced by the used Kernel (CT). The NPS values are limited to an intra system comparison due to the insufficient HU accuracy. The 3 D accuracy is comparable in between the system types. CONCLUSIONS: The values of image quality are not yet correlated with dose values: NPS. Investigations to an appropriate dosimetry are ongoing to establish the ratio between dose and image quality (ALARA principle). No fundamental difference between the systems can be stated in respect radio therapeutic planning: improper HU calibration accuracy in CBCT and DVT units. The geometric 3 D accuracy of high performance DVT systems is greater than that of CT Systems. PMID- 22076797 TI - [Carotid artery agenesis: anatomic normal variant or a risk for the patient?]. PMID- 22076798 TI - Synthesis of 5-alkyl[3,4-c]thienopyrrole-4,6-dione-based polymers by direct heteroarylation. PMID- 22076799 TI - Improvement in survival during the past 4 decades among patients with anterior skull base cancer. AB - BACKGROUND: The aims of this study were to determine the trends in survival of patients with anterior skull base cancer over several decades and to identify time-related changes in the demographic and clinical characteristics of this population. METHODS: In all, 282 patients who underwent craniofacial resection at Memorial Sloan-Kettering Cancer Center and Tel Aviv Medical Center were studied. Patients were categorized in accord with the period of surgery: early (1973-1984, n = 34), intermediate (1985-1996, n = 72), and later (1997-2008, n = 176). RESULTS: Patients operated after 1996 had higher rates of comorbidity, dural and pterygopalatine invasion, and multicompartmental involvement than those operated before 1996 (p <= .001). There was a significant improvement in 5-year overall and disease-specific survival, from 55% and 57%, respectively, for patients operated before 1996, to 66% and 70%, respectively, for those operated after 1996 (p = .02 and p = .006, respectively). On multivariate analysis, surgery after 1996 was an independent predictor of outcome (HR, 0.39, p < .001). CONCLUSIONS: The survival of patients with anterior skull base cancer is improving. Surgery after 1996 is an independent prognostic factor for an improved outcome. PMID- 22076801 TI - Glycotranscriptome study reveals an enzymatic switch modulating glycosaminoglycan synthesis during B-cell development and activation. AB - B-cell fate and responses are modulated by soluble mediators and direct cellular interactions. Migration properties also vary during differentiation, commitment and activation. In many cells, modulation of responses to stimuli involves cell surface glycans, whose architecture depends on the simultaneous expression of multiple enzymes. By looking at the glycosylation-related gene expression patterns among B-cell populations, we determined in this study that the strongest variations were observed for CSGalNAcT-1 and EXTL1. These are enzymes involved in the biosynthesis of alternative forms of glycosaminoglycans (GAGs), namely chondroitin sulfate and heparan sulfate, respectively. These two enzymes showed inverse fluctuations in progenitors, resting B cells and activated B cells, suggesting a developmentally regulated switch between chondroitin and heparan sulfate synthesis. To explore whether these variations contributed to optimal B cell differentiation, we overexpressed EXTL1 in the B-cell lineage of transgenic mice, yielding a partial differentiation blockade at the pro-B to pre-B transition. In the periphery, this defect was almost fully compensated for in vivo, with normal-size B-cell compartments and normal serum immunoglobulin levels in the transgenic EXTL1 mice. The peripheral B cells from EXTL1 transgenics were only affected with regard to their in vitro responses to polyclonal activation, showing reduced proliferation. Together the data suggest that despite their low amounts in lymphocytes, the heparan sulfate chains decorating the endogenous GAGs appear to be regulators of B-cell physiology. PMID- 22076800 TI - Suppression of calbindin-D28k expression exacerbates SCA1 phenotype in a disease mouse model. AB - Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder caused by the expansion of a polyglutamine tract in the mutant protein ataxin-1. The cerebellar Purkinje cells (PCs) are the major targets of mutant ataxin-1. The mechanism of PC death in SCA1 is not known; however, previous work indicates that downregulation of specific proteins involved in calcium homeostasis and signaling by mutant ataxin-1 is the probable cause of PC degeneration in SCA1. In this study, we explored if targeted deprivation of PC specific calcium-binding protein calbindin-D28k (CaB) exacerbates ataxin-1 mediated toxicity in SCA1 transgenic (Tg) mice. Using behavioral tests, we found that though both SCA1/+ and SCA1/+: CaB null (-/+) double mutants exhibited progressive impaired performance on the rotating rod, a simultaneous enhancement of exploratory activity, and absence of deficits in coordination, the double mutants were more severely impaired than SCA1/+ mice. With increasing age, SCA1/+ mice showed a progressive loss in the expression and localization of CaB and other PC specific calcium-binding and signaling proteins. In double mutants, these changes were more pronounced and had an earlier onset. Gene expression profiling of young mice exhibiting no behavior or biochemical deficits revealed a differential expression of many genes common to SCA1/+ and CaB-/+ lines, and unique to SCA1/+: CaB-/+ phenotype. Our study provides further evidence for a critical role of CaB in SCA1 pathogenesis, which may help identify new therapeutic targets to treat SCA1 or other cerebellar ataxias. PMID- 22076802 TI - Microfluidic synthesis of tunable poly-(N-isopropylacrylamide) microparticles via PEG adjustment. AB - We present a microfluidic droplet method to synthesize a series of tunable poly(N isopropylacrylamide) (PNIPAM) microparticles by the addition of polyethylene glycols (PEGs). The PEGs are used as porogens and could be removed simply by washing step. By varying molecular weights and concentrations of the PEGs, morphologies and temperature-sensitive properties of the formed PNIPAM microparticles are flexibly tuned. It is found that PEG of lower molecular weight induces smaller micropore sizes, and results in faster response rate. The volume changes prior to and after shrinkage can also be regulated by the addition of PEGs due to tuned homogeneities of micropores. The microparticles tuned by PEG1000 with ratio of added PEGs to NIPAM of 2:1 respond the fastest (120 s), whereas with ratio of added PEGs to NIPAM of 1:1 display largest volume change (1/gamma=12.12). This simplicity and controllability of tunable microparticles synthesis are appealing for various applications ranging from chemical delivery, drug release control, to optical applications. PMID- 22076803 TI - Host-guest geometry in pores of zeolite ZSM-5 spatially resolved with multiplex CARS spectromicroscopy. PMID- 22076804 TI - [Right coronary artery arising from the left coronary sinus with interarterial course in an asymptomatic newborn]. PMID- 22076805 TI - A search for SNCA 3' UTR variants identified SNP rs356165 as a determinant of disease risk and onset age in Parkinson's disease. AB - Alpha-synuclein gene (SNCA) polymorphisms have been associated with the common sporadic form of Parkinson's disease (PD). We searched for DNA variants at the SNCA 3' UTR through single strand conformation analysis and direct sequencing in a cohort of Spanish PD patients and controls. We have genotyped the rs356165 SNCA 3' UTR polymorphism in a total of 1,135 PD patients and 772 healthy controls from two Spanish cohorts (Asturias and Navarre). We identified six SNCA 3' UTR variants. Single nucleotide polymorphism (SNP) rs356165 was significantly associated with PD risk in the Spanish cohort (p = 0.0001; odd ratio = 1.37, 95%CI = 1.19-1.58). This SNP was also significantly associated with early age at onset of PD. Our work highlights rs356165 as an important determinant of the risk of developing PD and early age at onset and encourages future research to identify a functional effect on SNCA expression. PMID- 22076807 TI - Well-dispersed bi-component-active CoO/CoFe2O4 nanocomposites with tunable performances as anode materials for lithium-ion batteries. AB - CoO/CoFe(2)O(4) nanocomposites, derived from scalably prepared CoFe-layered double hydroxide (CoFe-LDH) single-resource precursors, exhibit tunable cycle performances and rate capabilities, which are supported by the homogenous dispersion of bi-component active CoO and CoFe(2)O(4) phases. PMID- 22076806 TI - Independent association of serum retinol and beta-carotene levels with hyperuricemia: A national population study. AB - OBJECTIVE: Uses of synthetic vitamin A derivatives (e.g., isotretinoin used for severe acne) and high doses of preformed vitamin A have been implicated in the pathogenesis of hyperuricemia and gout, whereas a trial reported that beta carotene may lower serum uric acid (UA) levels. We evaluated the potential population impact of these factors on serum UA in a nationally representative sample of US adults. METHODS: Using data from 14,349 participants ages >=20 years in the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between serum retinol, beta-carotene, and UA levels using weighted linear regression. Additionally, we examined the relationship with hyperuricemia using weighted logistic regression. RESULTS: Serum UA levels increased linearly with increasing serum retinol levels, whereas serum UA levels decreased with increasing serum beta-carotene levels. After adjusting for age, sex, dietary factors, and other potential confounders, the serum UA level differences from the bottom (referent) to the top quintiles of serum retinol levels were 0, 0.16, 0.32, 0.43, and 0.71 mg/dl (P for trend <0.001), and for beta-carotene were 0, -0.15, -0.29, -0.27, and -0.40 mg/dl (P for trend <0.001), respectively. Similarly, the multivariate odds ratios of hyperuricemia from the bottom (referent) to top quintiles of serum retinol levels were 1.00, 1.30, 1.83, 2.09, and 3.22 (P for trend <0.001) and for beta-carotene were 1.00, 0.85, 0.68, 0.73, and 0.54 (P for trend <0.001), respectively. The graded associations persisted across subgroups according to cross-classification by both serum retinol and beta-carotene levels. CONCLUSION: These nationally representative data raise concerns that vitamin A supplementation and food fortification may contribute to the high frequency of hyperuricemia in the US population, whereas beta-carotene intake may be beneficial against hyperuricemia. The use of beta carotene as a novel preventive treatment for gout deserves further investigation. PMID- 22076808 TI - Impairment of executive performance after transcranial magnetic modulation of the left dorsal frontal-striatal circuit. AB - The dorsal frontal-striatal circuit is implicated in executive functions, such as planning. The Tower of London task, a planning task, in combination with off-line low-frequency repetitive transcranial magnetic stimulation (rTMS), was used to investigate whether interfering with dorsolateral prefrontal function would modulate executive performance, mimicking dorsal frontal-striatal dysfunction as found in neuropsychiatric disorders. Eleven healthy controls (seven females; mean age 25.5 years) were entered in a cross-over design: two single-session treatments of low-frequency (1 Hz) rTMS (vs. sham rTMS) for 20 min on the left dorsolateral prefrontal cortex (DLPFC). Directly following the off-line rTMS treatment, the Tower of London task was performed during MRI measurements. The low-frequency rTMS treatment impaired performance, but only when the subjects had not performed the task before: we found a TMS condition-by-order effect, such that real TMS treatment in the first session led to significantly more errors (P = 0.032), whereas this TMS effect was not present in subjects who received real TMS in the second session. At the neural level, rTMS resulted in decreased activation during the rTMS versus sham condition in prefrontal brain regions (i.e., premotor, dorsolateral prefrontal and anterior prefrontal cortices) and visuospatial brain regions (i.e., precuneus/cuneus and inferior parietal cortex). The results show that low-frequency off-line rTMS on the DLPFC resulted in decreased task-related activations in the frontal and visuospatial regions during the performance of the Tower of London task, with a behavioral effect only when task experience is limited. PMID- 22076809 TI - Unexpected influence of stereochemistry on the cytotoxicity of highly efficient Ti(IV) salan complexes: new mechanistic insights. AB - The effect of stereochemistry on the cytotoxicity of highly active and hydrolytically stable N-methylated Ti(IV) salan complexes is reported. Four bis(isopropoxo) complexes incorporating N-methylated salan ligands with different aromatic substitution patterns have been prepared in racemic and optically active forms for the first time by ligand-to-metal chiral induction from trans diaminocyclohexyl-based chiral ligands. The configuration of the metal center that derives from that of the ligand has an enormous influence on cytotoxicity, with the racemic mixture mostly being more active than the single enantiomers that are of either similar or different activity. This implies that the active species is a salan-bound heterochiral polynuclear compound, interacting with a chiral target. Four additional complexes of achiral salan and chiral labile sec butoxo ligands, analyzed as racemic and as homochiral, revealed no influence of stereochemistry, supporting early dissociation of the labile ligands to give the polynuclear products. PMID- 22076810 TI - Comparative impact of an anthranilic diamide and other insecticidal chemistries on beneficial invertebrates and ecosystem services in turfgrass. AB - BACKGROUND: Chlorantraniliprole, the first anthranilic diamide insecticide labeled for turf, combines strong selective activity against key pests with low vertebrate toxicity. The hypothesis that it is less disruptive to beneficial invertebrates and their ecosystem services than are other prevailing insecticide classes was tested. Plots in golf course settings were treated with chlorantraniliprole, or with a representative nicotinoid (clothianidin), pyethroid (bifenthrin) or a combination (clothianidin-bifenthrin) formulation. Non-target effects were assessed via pitfall traps (epigeal predators), Tullgren funnel extraction (soil microarthropods), hand sorting (earthworms), counting ant mounds and earthworm casts on tees and putting greens, assessing predation on sentinel pest eggs and comparing grass clipping decomposition in treated versus untreated turf. RESULTS: Chlorantraniliprole had little or, in most cases, no impact on predatory or soil invertebrates, predation or decomposition. Each of the other insecticides temporarily reduced abundance and activity of one or more predator groups. Clothianidin and the clothianidin-bifenthrin combination retarded grass clipping decomposition, and the combination suppressed earthworms and casts more than did carbaryl, a toxic standard. CONCLUSION: Chlorantraniliprole is compatible with conservation biocontrol and a good fit for industry initiatives to use relatively less toxic pesticides. One caveat is that its use on golf courses may require targeted management of ant mounds and earthworm casts that are suppressed as a side effect by some less selective insecticides. PMID- 22076811 TI - Dosimetric comparison of three different external beam whole breast irradiation techniques. AB - INTRODUCTION: The purpose of this study was to compare the dosimetries of three different external beam whole breast radiotherapy techniques: two-dimensional RT (2D-RT), three-dimensional conformal RT (3D-CRT), and field-in-field intensity modulated RT (FiF-IMRT). In addition, we aimed to evaluate the patients who needed more or less complex treatment modalities. METHODS: Thirty patients were included in the study. All the patients had early-stage breast cancer and conserving surgery had been performed. Plans that employed the three techniques were generated for each patient. Dosimetric comparisons were conducted, and correlations with patient characteristics and dosimetric outcomes were analyzed. RESULTS: The 2D-RT technique was found to be suboptimal for treating the intact breast. Its dose homogeneity index (DHI) was 20.68. The authors were unable to define a patient characteristic in which 2D-RT dosimetry would perform better. FiF-IMRT was found to be the superior technique with a better homogeneity in the breast (DHI=9.35 and P=0.000002 when compared to 3D-CRT). When compared according to patient characteristics, again the FiF-IMRT planning is the best for all subgroups, but the DHI gets worse by increased breast volume and separation. While FiF-IMRT achieves better DHI in the breast, it has little effect on heart and lung doses. But the normal tissues' volume (cc) that gets the 100% of the prescribed dose (V100) was lowered because of the treatment without wedges and scatter and with less monitor unit. CONCLUSIONS: 2D-RT could not be performed safely on the intact breast in any of the subgroups. FiF-IMRT is a superior technique for breast dosimetry, and normal tissue. For patients with large breast size or separation, further intensive techniques must be investigated. PMID- 22076812 TI - Stereotactic body radiation therapy for locally recurrent, previously irradiated nonsquamous cell cancers of the head and neck. AB - BACKGROUND: Stereotactic body radiotherapy (SBRT) has emerged as a promising salvage strategy for patients with recurrent, previously irradiated head and neck cancer; however, data are limited predominantly to squamous cell carcinomas. Herein, we report the efficacy of SBRT in recurrent, nonsquamous cell cancers of the head and neck (NSCHNs). METHODS: In all, 34 patients with pathologically proven NSCHN were re-irradiated with SBRT to a median dose of 40 Gy in 5 fractions (interquartile range, 30-44 Gy). Toxicity and quality of life were followed prospectively. RESULTS: Median follow-up was 10 months (absolute range, 0-55 months). The 6-month/1-year local control rate was 77/59%, with a 6-month/1 year overall survival of 76/59%. Local control was significantly improved for tumors <25 mL (p = .030). Acute/late grade 3 toxicity was 15/6%, with no grade 4 5 toxicity. CONCLUSIONS: SBRT for previously irradiated, locally recurrent NSCHN provides promising local control, especially for tumors <25 mL, with minimal toxicity. The optimal dose for larger tumors remains to be defined. PMID- 22076813 TI - Microfabricated particulate drug-delivery systems. AB - Micro- and nanoparticulate drug-delivery systems (DDSs) play a significant role in formulation sciences. Most particulate DDSs are scaffold-free, although some particles are encapsulated inside other biomaterials for controlled release. Despite rapid progress in recent years, challenges still remain in controlling the homogenicity of micro-/nanoparticles, especially for two crucial factors in particulate DDSs: the size and shape of the particles. Recent approaches make use of microfabrication techniques to generate micro-/nanoparticles with highly controllable architectures free of scaffolds. This review presents an overview of a burgeoning field of DDSs, which can potentially overcome some drawbacks of conventional techniques for particle fabrication and offer better control of particulate DDSs. PMID- 22076815 TI - New functionalities in the GROMOS biomolecular simulation software. AB - Since the most recent description of the functionalities of the GROMOS software for biomolecular simulation in 2005 many new functions have been implemented. In this article, the new functionalities that involve modified forces in a molecular dynamics (MD) simulation are described: the treatment of electronic polarizability, an implicit surface area and internal volume solvation term to calculate interatomic forces, functions for the GROMOS coarse-grained supramolecular force field, a multiplicative switching function for nonbonded interactions, adiabatic decoupling of a number of degrees of freedom with temperature or force scaling to enhance sampling, and nonequilibrium MD to calculate the dielectric permittivity or viscosity. Examples that illustrate the use of these functionalities are given. PMID- 22076814 TI - CCL2: a potential prognostic marker and target of anti-inflammatory strategy in HIV/AIDS pathogenesis. AB - Chemokines are critical components of the immune system that participate in immune homeostasis and alterations in chemokine balance can result in severe inflammatory and autoimmune diseases. The role of chemokines and their receptors in viral infections including HIV-1 was predicted from the early studies of HIV-1 co-receptor CCR5 and its ligands and a divergent role of C-C chemokines in HIV-1 pathogenesis has been established. For example, CCL3 (MIP-1alpha), CCL4 (MIP 1beta) and CCL5 (RANTES) have been shown to possess antiviral effects by binding to the HIV-1 co-receptor CCR5, whereas CCL2, a pro-inflammatory chemokine, supports HIV-1 replication despite being a member of same chemokine family. Furthermore, the well-established role of CCL2 in driving the Th2 immune response supports its potential role in HIV-1/AIDS. Recent reports suggest multiple pathways of CCL2 affect HIV-1 infection. In this review, we provide a comprehensive overview of the role and potential mechanisms of the HIV-1-CCL2 interplay in driving virus-induced immuno-pathology, suggesting that CCL2 could be an anti-inflammatory target in the treatment of HIV-1 infection. PMID- 22076816 TI - A new fluorescent PET probe for hydrogen peroxide and its use in enzymatic assays for L-lactate and D-glucose. AB - We present a new probe for the determination of hydrogen peroxide (HP). It is based on the yellow fluorophore 4-amino-1,8-napththalimide, coupled to p anisidine (as a redox-active group) to form a probe that is based on photoinduced electron transfer (PET). The preparation of the probe (which we refer to as "HP Green") was accomplished in four steps with good yield. Its fluorescence is independent of pH in the physiological range and quenched by a PET process that occurs between the p-anisidine redox moiety and the naphthalimide luminophore. If the p-anisidine group is oxidized by HP, PET is suppressed and fluorescence intensity is strongly increased. Addition of horseradish peroxidase (HRP) enhances the oxidation of HP Green and further improves the detection limit of HP. The use of HRP and HP Green enables the determination of HP concentration in a range of 0.1 to 5 MUM, with a limit of detection (LOD) as low as 64 nM (16 pmol per well in microtiter plates). HP Green and HRP also enable sensitive enzymatic assays of oxidase substrates in a kinetic format, as shown for L-lactate and D glucose. L-Lactate concentration can be rapidly determined between 0.5 and 10 MUM after 6 minutes of incubation at 30 degrees C, with an LOD of 164 nm (41 pmol per well). This LOD is more than sixfold lower than that of the best commercial assays for lactate. The detection range for D-glucose is 2 to 30 MUm, and the LOD is 644 nM (161 pmol per well). These are among the lowest concentrations detectable for oxidase-based assays. The hexanoic acid moiety in HP Green may be further used to immobilize the probe in order to obtain sensor layers for continuous assays. PMID- 22076818 TI - Surface acoustic wave sensing of linear alcohols using para-acylcalix[n]arenes. AB - para-Hexanoylcalix[4, 6 or 8]arenes have been used as surface acoustic wave sensor capture layers showing a high efficiency for the detection of linear alcohols, with high reproducibility and rapid response times. PMID- 22076819 TI - Practical approach to screening for scleroderma-associated pulmonary arterial hypertension. PMID- 22076820 TI - Toxicity and horizontal transfer of chlorantraniliprole against the Asian subterranean termite Coptotermes gestroi (Wasmann): effects of donor:recipient ratio, exposure duration and soil type. AB - BACKGROUND: The effectiveness of chlorantraniliprole and other insecticides (bifenthrin, fipronil, indoxacarb, imidacloprid and chlorfenapyr) were tested against Coptotermes gestroi (Wasmann). Four experiments were conducted: a topical bioassay, a horizontal transfer study, an insecticide bioavailability test and a feeding bioassay. RESULTS: The topical bioassay showed that chlorantraniliprole was significantly less active to C. gestroi at 24 h post-treatment compared with the other insecticides tested. Nevertheless, it is likely that a lesser amount of chlorantraniliprole was required to cause 50% mortality of C. gestroi at 7 and 14 days post-treatment. The exposure duration and donor:recipient ratio affect the mortality of recipient termites. Mortality after exposure to chlorantraniliprole in sandy clay was significantly lower than in sand; however, by 14 days, > 90% of donor and recipient termites died in both substrates, irrespective of concentration. Fipronil and imidacloprid showed faster action, and high to moderate toxicity to C. gestroi. Termite workers also ceased to feed after exposure for 1 h to 50 mg kg(-1) chlorantraniliprole-treated sandy clay. CONCLUSION: Chlorantraniliprole demonstrated delayed toxicity at the lowest label rate (50 mg kg(-1) ) in sandy clay. Its slow action will enable greater transfer of toxicant between nestmates, while feeding cessation will promote greater social interaction between healthy and exposed termites. PMID- 22076821 TI - Catalytic 1,3-difunctionalisation of organic backbones through a highly stereoselective, one-pot, boron conjugate-addition/reduction/oxidation process. AB - A simple one-pot, three-step synthetic route to chiral 1,3-amino alcohols and 1,3 diols has been established. Considering the overall stereocontrol of the synthetic protocol, the first and key step is an enantioselective beta-boration of alpha,beta-unsaturated imines and ketones, respectively. The enantioselectivity provided by the Cu(I) catalyst modified with Josiphos- and Mandyphos-type ligands has been examined. The oxidative substitution of the boryl unit with a hydroxyl group proceeds with complete retention of configuration at the C(beta)-atom. In parallel, the stoichiometric reduction of the imino or carbonyl group provides a second stereogenic centre. Depending on the nature of the reducing reagent, exceptionally high diastereoselectivity is achieved, especially for syn-1,3-amino alcohols and 1,3-diols. PMID- 22076822 TI - An endoscopic endonsal transethmoidal approach to olfactory groove meningioma. PMID- 22076823 TI - Functional brain connectivity at rest changes after working memory training. AB - Networks of functional connectivity are highly consistent across participants, suggesting that functional connectivity is for a large part predetermined. However, several studies have shown that functional connectivity may change depending on instructions or previous experience. In the present study, we investigated whether 6 weeks of practice with a working memory task changes functional connectivity during a resting period preceding the task. We focused on two task-relevant networks, the frontoparietal network and the default network, using seed regions in the right middle frontal gyrus (MFG) and the medial prefrontal cortex (PFC), respectively. After practice, young adults showed increased functional connectivity between the right MFG and other regions of the frontoparietal network, including bilateral superior frontal gyrus, paracingulate gyrus, and anterior cingulate cortex. In addition, they showed reduced functional connectivity between the medial PFC and right posterior middle temporal gyrus. Moreover, a regression with performance changes revealed a positive relation between performance increases and changes of frontoparietal connectivity, and a negative relation between performance increases and changes of default network connectivity. Next, to study whether experience-dependent effects would be different during development, we also examined practice effects in a pilot sample of 12-year-old children. No practice effects were found in this group, suggesting that practice-related changes of functional connectivity are age-dependent. Nevertheless, future studies with larger samples are necessary to confirm this hypothesis. PMID- 22076824 TI - Resolution adapted finite element modeling of radio frequency interactions on conductive resonant structures in MRI. AB - Prediction of interactions between the radiofrequency electromagnetic field in magnetic resonance scanners and electrically conductive material surrounded by tissue plays an increasing role for magnetic resonance safety. Testing of conductive implants or instruments is usually performed by standardized experimental setups and temperature measurements at distinct geometrical points, which cannot always reflect worst-case situations. A finite element method based on Matlab (The Mathworks, Natick, MA) and the finite element method program Comsol Multiphysics (Stockholm, Sweden) with a spatially highly variable mesh size solving Maxwell's full-wave equations was applied for a comprehensive simulation of the complete geometrical arrangement of typical birdcage radiofrequency coils loaded with small conductive structures in a homogenous medium. Conductive implants like rods of variable length and closed and open ring structures, partly exhibiting electromagnetic resonance behavior, were modeled and evaluated regarding the distribution of the B(1)- and E-field, induced currents and specific absorption rates. Numerical simulations corresponded well with experiments using a spin-echo sequence for visualization of marked B(1) field inhomogeneities. Even resonance effects in conductive rods and open rings with suitable geometry were depicted accurately. The proposed method has high potential for complementation or even replacement of common experimental magnetic resonance compatibility measurements. PMID- 22076826 TI - Quantitative relationship between coronary artery calcium score and hyperemic myocardial blood flow as assessed by hybrid 15O-water PET/CT imaging in patients evaluated for coronary artery disease. AB - BACKGROUND: The incremental value of CAC over traditional risk factors to predict coronary vasodilator dysfunction and inherent myocardial blood flow (MBF) impairment is only scarcely documented (MBF). The aim of this study was therefore to evaluate the relationship between CAC content, hyperemic MBF, and coronary flow reserve (CFR) in patients undergoing hybrid (15)O-water PET/CT imaging. METHODS: We evaluated 173 (mean age 56 +/- 10, 78 men) patients with a low to intermediate likelihood for coronary artery disease (CAD), without a documented history of CAD, undergoing vasodilator stress (15)O-water PET/CT and CAC scoring. Obstructive coronary artery disease was excluded by means of invasive (n = 44) or CT-based coronary angiography (n = 129). RESULTS: 91 of 173 patients (52%) had a CAC score of zero. Of those with CAC, the CAC score was 0.1-99.9, 100-399.9, and >=400 in 31%, 12%, and 5% of patients, respectively. Global CAC score showed significant inverse correlation with hyperemic MBF (r = -0.32, P < .001). With increasing CAC score, there was a decline in hyperemic MBF on a per-patient basis [3.70, 3.30, 2.68, and 2.53 mL . min(-1) . g(-1), with total CAC score of 0, 0.1 99.9, 100-399.9, and >=400, respectively (P < .001)]. CFR showed a stepwise decline with increasing levels of CAC (3.70, 3.32, 2.94, and 2.93, P < .05). Multivariate analysis, including age, BMI, and CAD risk factors, revealed that only age, male gender, BMI, and hypercholesterolemia were associated with reduced stress perfusion. Furthermore, only diabetes and age were independently associated with CFR. CONCLUSION: In patients without significant obstructive CAD, a greater CAC burden is associated with a decreased hyperemic MBF and CFR. However, this association disappeared after adjustment for traditional CAD risk factors. These results suggest that CAC does not add incremental value regarding hyperemic MBF and CFR over established CAD risk factors in patients without obstructive CAD. PMID- 22076827 TI - Relationship between paraglottic space invasion and cervical lymph node metastasis in patients undergoing supracricoid partial laryngectomy. AB - BACKGROUND: To investigate the relationship between paraglottic space (PGS) invasion and lymph node metastasis in patients undergoing supracricoid partial laryngectomy. METHODS: The study included 98 subjects with squamous cell carcinoma of the glottis. RESULTS: The PGS invasion rate was 60.2% (59/98), and a significant correlation was found between PGS invasion and cervical lymph node metastasis (p = .022). Fifteen of the 59 patients (25.4%) with PGS invasion, only 3 of the 39 patients (7.7%) without any evidence of PGS invasion had lymph node metastasis. Furthermore, a significant correlation was also found between PGS invasion and T classification (p < .001), vocal cord mobility (p < .001), and subglottic extension (p = .014), and patients with no evidence of PGS invasion possibly had a survival benefit (5-year disease-specific survival rate, 84% vs 64%; p = .118). CONCLUSION: This study shows that PGS invasion is significantly related to cervical lymph node metastasis in patients undergoing supracricoid partial laryngectomy. PMID- 22076828 TI - The ribosomal exit tunnel as a target for optimizing protein expression in Escherichia coli. AB - The folding of many cellular proteins occurs co-translationally immediately outside the ribosome exit tunnel, where ribosomal proteins and other associated factors coordinate the synthesis and folding of newly translated polypeptides. Here, we show that the large subunit protein L29, which forms part of the exit tunnel in Escherichia coli, is required for the productive synthesis of an array of structurally diverse recombinant proteins including the green fluorescent protein (GFP) and an intracellular single-chain Fv antibody. Surprisingly, the corresponding mRNA transcript level of these proteins was markedly less abundant in cells lacking L29, suggesting an unexpected regulatory mechanism that links defects in the exit tunnel to the expression of genetic information. To further highlight the importance of L29 in maintaining protein expression, we used mutagenesis and selection to obtain L29 variants that enhanced GFP expression. Overall, our results suggest that the ribosomal exit tunnel proteins may be key targets for optimizing the overproduction of active, structurally complex recombinant proteins in bacterial cells. PMID- 22076829 TI - Synthetic virus-like particles and conformationally constrained peptidomimetics in vaccine design. AB - Conformationally constrained peptidomimetics could be of great value in the design of vaccines targeting protective epitopes on viral and bacterial pathogens. But the poor immunogenicity of small synthetic molecules represents a serious obstacle for their use in vaccine development. Here, we show how a constrained epitope mimetic can be rendered highly immunogenic through multivalent display on the surface of synthetic virus-like nanoparticles. The target epitope is the V3 loop from the gp120 glycoprotein of HIV-1 bound to the neutralizing antibody F425-B4e8. The antibody-bound V3 loop adopts a beta-hairpin conformation, which is effectively stabilized by transplantation onto a D-Pro-L Pro template. The resulting mimetic after coupling to synthetic virus-like particles elicited antibodies in rabbits that recognized recombinant gp120. The elicited antibodies also blocked infection by the neutralization sensitive tier-1 strain MN of HIV-1, as well as engineered viruses with the V1V2 loop deleted; this result is consistent with screening of V3 by the V1V2 loop in intact trimeric viral gp120 spikes. The results provide new insights into HIV-1 vaccine design based on the V3 loop, and illustrate how knowledge from structural biology can be exploited for the design of constrained epitope mimetics, which can be delivered to the immune system by using a highly immunogenic synthetic nanoparticle delivery system. PMID- 22076830 TI - Efficient synthesis of biazoles by aerobic oxidative homocoupling of azoles catalyzed by a copper(I)/2-pyridonate catalytic system. AB - A highly efficient and convenient CuCl/2-pyridonate catalytic system for oxidative homocoupling of azoles affording a biazole product has been developed. With this system, a variety of biazoles have been effectively synthesized in good to excellent yields in the presence of a very small amount of copper catalyst (1.0 mol%). It was feasible to employ air as a green oxidant. PMID- 22076831 TI - Th1/Th2 cytokine profiles in G+/G- bacteremia in pediatric hematology/oncology patients. AB - BACKGROUND: Early diagnosis of infection and appropriate choice of antibiotics are essential not only to improve the prognosis of the patients but also to prevent from the abuse of the antibiotics in hematology/oncology children at the time of neutropenia after intensive chemotherapy. PROCEDURE: We evaluated the quantification of Th1/Th2 cytokines with flow cytometry bead assay (CBA) in 145 hospitalized febrile hematology/oncology children with positive blood culture to seek for a rapid diagnostic method to determine the type of infection. RESULTS: IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma levels from both G- and G+ bacteremia groups were significantly higher than those of controls (P < 0.001). The median levels of IL-6, IL-10, TNF-alpha of Group G- were 525.4, 96.0, and 6.9 pg/ml, respectively, significantly higher than those of Group G+ (150.0, 22.6, and 4.5 pg/ml, respectively, P < 0.001). According to the different degrees of increased IL-6 and IL-10 levels, we named the G- bacterial infection related cytokine profile G- BIRCP and the G+ BIRCP. The specificity and sensitivity of BIRCP prediction for G- and G+ bacteria cultures were 60.2% and 75.4%, 66.8% and 70.1%, respectively. Similar therapeutic efficacy was achieved between BIRCP-based and broad-spectrum antibiotics groups (86.1% vs. 89.3%, P > 0.05), which was significantly increased as compared with that (65.5%, P < 0.05) of empirical group. CONCLUSIONS: These results showed the promising use of the IL-6/IL-10/TNF alpha determination with CBA technology for the early and rapid diagnosis, evaluation of G+/G- bacteremia in pediatric hematology/oncology patients. PMID- 22076832 TI - Therapeutic complications in a patient with high-risk acute lymphoblastic leukemia and undiagnosed hereditary hemochromatosis. AB - Hereditary hemochromatosis (HH) is an autosomal-recessive disorder of iron metabolism that most commonly manifests in the fourth or fifth decade of life. Here, we describe a 14-year-old male who presented with high-risk acute lymphoblastic leukemia and previously undiagnosed HH. His treatment course was remarkable for significant therapeutic complications, including iron overload, hepatic failure, cardiac dysfunction, and death. Postmortem testing revealed homozygosity for the C282Y mutation, confirming the diagnosis of HH. Since HH mutations occur commonly in select populations, screening patients with leukemia for HH may better inform treatment decisions regarding chemotherapy, transfusions, and/or iron chelation therapy. PMID- 22076833 TI - Oral low-dose chemotherapy: successful treatment of an alveolar rhabdomyosarcoma during pregnancy. AB - We report for the first time the impact of neoadjuvant oral low-dose chemotherapy consisting of oral trofosfamide, idarubicin, and etoposide (O-TIE) in the case of alveolar rhabdomyosarcoma (RMS) in the lower jaw of an 18-year-old woman at 27 weeks of gestation, without fetal complications and a highly efficient anti-tumor response. Our study suggests the possible application of O-TIE treatment in a neoadjuvant setting during pregnancy and recommends a schedule that can be considered for the treatment of patients with high-risk sarcomas who cannot be treated with intensive chemotherapy for various reasons. PMID- 22076834 TI - Health consequences of obesity. AB - Epidemiologic studies have established that cardiovascular (CV) risk factors including obesity are identifiable in childhood. Childhood risk factors are predictive of adult cardiac risk and even premature death [Franks et al. (2010) N Engl J Med 362:485-493]. In the United States, CV diseases remains the leading causes of death. In fact, heart disease has become the major cause of death worldwide, surpassing undernutrition and infectious diseases, largely related to obesity in childhood [Wang and Lobstein (2006) Int J Pediatr Obes 1:11-25]. The concept that adult heart diseases begin in childhood is an outgrowth of extensive long-term epidemiologic studies in youth, that is, the Bogalusa Heart Study [Berenson et al. (1986) Causation of cardiovascular risk factors in children: Perspectives on cardiovascular risk in early life, Raven Press Books Ltd]. PMID- 22076836 TI - Influence of discipline of provider and model of care on an arthritis educational intervention in primary care. AB - OBJECTIVE: To identify both provider and organizational characteristics that predicted outcomes following an educational intervention (9-hour workshop and followup reinforcement activities) developed to improve the management of arthritis in primary care. METHODS: Providers completed a survey at baseline and at 6 months postworkshop, including a case scenario for early rheumatoid arthritis. Providers were asked how they would manage the case and their responses were coded to calculate a best practice score, ranging from 0-7. Two level hierarchical linear modeling was used to determine which of the measured provider and organizational factors predicted best practice scores at followup. RESULTS: A total of 275 multidisciplinary providers from 131 organizations completed both baseline and followup surveys. Best practice scores increased by 17% (P < 0.01); however, the mean score at 6-month followup remained relatively low (2.68). Significant predictors of best practice scores at followup were discipline of provider and model of primary care in which they worked (P < 0.05), adjusting for baseline practice scores and clustering of providers within organizations. Physicians, nurse practitioners, and rehabilitation therapists scored higher than nurses, students, and other health care providers (P < 0.01). Physician networks scored significantly lower than providers from multidisciplinary-oriented models of care (P = 0.02). CONCLUSION: These results have implications for the education of health professionals and the design of models of care to enhance arthritis care delivery. PMID- 22076835 TI - The endocannabinoid system: role in energy regulation. AB - Cannabis sativa has been used since antiquity to treat many ailments, including eating disorders. The primary psychoactive constituent of this plant, Delta(9) tetrahydrocannabinol (THC) is an FDA approved medication to treat nausea and emesis caused by cancer chemotherapeutic agents as well as to stimulate appetite in AIDS patients suffering from cachexia. The effects of THC are mediated through the endocannabinoid system (ECS), which promotes a positive energy balance through stimulation of appetite as well as shifting homeostatic mechanisms toward energy storage. Here we discuss the physiological function of the ECS in energy balance and the therapeutic potential of targeting this system. PMID- 22076837 TI - A unified strategy for the asymmetric total syntheses of diversonol and lachnone C. AB - A unified synthetic strategy for the asymmetric syntheses of the natural products diversonol and lachnone C was developed by using the domino vinylogous aldol-oxa Michael reaction as the enantioselective key step. Further transformations include dihydroxylation, lactol-opening by a Wittig-reaction, and lactonization. The obtained chromone lactones, a class of mycotoxins, can further be converted to tetrahydroxanthones by a Dieckmann condensation. This general method allows for the first time the enantioselective access to these classes of natural products and should be applicable to other members of the tetrahydroxanthone and chromone lactone families. PMID- 22076838 TI - NMR study on iridium(III) complexes for identifying disulfonate substituted bathophenanthroline regio-isomers. AB - A series of novel biscyclometalated iridium (III) complexes with an ancillary disulfonated bathophenanthroline (DSBP(2-)) ligand, Ir(L)(2)DSBPNa, L = 2 phenylpyridine (ppy), 2,4-difluorophenylpyridine (fppy), and 1-phenylisoquinoline (piq) were found to have two isomeric forms. The chemical structures of the isomers were determined by the one- and two-dimensional (1)H and (13)C NMR studies. The isomeric state was proved to have originated from the disulfonate related regio-isomer of the DSBP(2-) ligand. PMID- 22076839 TI - Epidermoid tumor of the cerebellopontine angle presenting with selective sudden hearing loss. Intraoperative evidence of a pearl tumor infiltrating and compressing the cochlear nerve. AB - Epidermoid tumors of the cerebellopontine angle are associated with a variety of symptoms, usually attributed to compression and displacement of involved cranial nerves. The authors present a case of a large epidermoid tumor in the left cerebellopontine angle with sudden hearing loss and tinnitus. The intraoperative finding of migration of two tumor pearls into the cochlear nerve was the origin of the clinical sign. The patient improved remarkably after removal of the tumor. This case demonstrates the mechanism for selective hearing loss associated with the large cerebellopontine angle. PMID- 22076840 TI - Common structural correlates of trait impulsiveness and perceptual reasoning in adolescence. AB - BACKGROUND: Trait impulsiveness is a potential factor that predicts both substance use and certain psychiatric disorders. This study investigates whether there are common structural cerebral correlates of trait impulsiveness and cognitive functioning in a large sample of healthy adolescents from the IMAGEN project. METHODS: Clusters of gray matter (GM) volume associated with trait impulsiveness, Cloningers' revised temperament, and character inventory impulsiveness (TCI-R-I) were identified in a whole brain analysis using optimized voxel-based morphometry in 115 healthy 14-year-olds. The clusters were tested for correlations with performance on the nonverbal tests (Block Design, BD; Matrix Reasoning, MT) of the Wechsler Scale of Intelligence for Children IV reflecting perceptual reasoning. RESULTS: Cloningers' impulsiveness (TCI-R-I) score was significantly inversely associated with GM volume in left orbitofrontal cortex (OFC). Frontal clusters found were positively correlated with performance in perceptual reasoning tasks (Bonferroni corrected). No significant correlations between TCI-R-I and perceptual reasoning were observed. CONCLUSIONS: The neural correlate of trait impulsiveness in the OFC matches an area where brain function has previously been related to inhibitory control. Additionally, orbitofrontal GM volume was associated with scores for perceptual reasoning. The data show for the first time structural correlates of both cognitive functioning and impulsiveness in healthy adolescent subjects. PMID- 22076842 TI - Unpureeing the tomato: layers of information revealed by microdissection and high throughput transcriptome sequencing. PMID- 22076841 TI - Comparison of the effects of continuous and pulsatile left ventricular-assist devices on ventricular unloading using a cardiac electromechanics model. AB - Left ventricular-assist devices (LVADs) are used to supply blood to the body of patients with heart failure. Pressure unloading is greater for counter-pulsating LVADs than for continuous LVADs. However, several clinical trials have demonstrated that myocardial recovery is similar for both types of LVAD. This study examined the contractile energy consumption of the myocardium with continuous and counter-pulsating LVAD support to ascertain the effect of the different LVADs on myocardial recovery. We used a three-dimensional electromechanical model of canine ventricles, with models of the circulatory system and an LVAD. We compared the left ventricular peak pressure (LVPP) and contractile ATP consumption between pulsatile and continuous LVADs. With the continuous and counter-pulsating LVAD, the LVPP decreased to 46 and 10%, respectively, and contractile ATP consumption decreased to 60 and 50%. The small difference between the contractile ATP consumption of these two types of LVAD may explain the comparable effects of the two types on myocardial recovery. PMID- 22076843 TI - Free tissue transfer for head and neck reconstruction in solid organ transplant patients. AB - BACKGROUND: Patients with head and neck malignancies who have had solid organ transplant and require free tissue transfer are a unique population. This study was performed to evaluate the effect of immunosuppression on the rate of perioperative complications and the success of free tissue transfer in the head and neck. METHODS: Complications in solid organ transplant patients undergoing free tissue transfer for reconstruction of head and neck malignancies from 1998 to 2010 were evaluated. RESULTS: A total of 22 flaps in 17 patients were performed. Eight patients (11 of 22 flaps) had complications. The median hospital stay was 6 days (range, 4-26 days). The median length of follow-up was 13.5 months (range, 3.5-49.9 months). CONCLUSIONS: Solid organ transplant patients are at an increased risk of de novo malignancies due to chronic immunosuppression. This study demonstrates that free tissue transfer is a viable option in transplant patients with morbidity similar to nontransplant patients. PMID- 22076844 TI - Screening of cell-penetrating peptides using mRNA display. AB - Cell-penetrating peptides (CPPs) are attractive vectors for in vivo and in vitro cellular uptake. Their use is, however, limited by insufficient understanding of their preference for a target cell. Here, a new CPP screening method is presented that uses mRNA display. After incubating the target cell lines, such as human embryonic kidney 293 (HEK 293) and HeLa cells, with an mRNA display library for 3 h at 37 degrees C, the CPP-mRNA nucleotide conjugates were harvested. These were amplified with PCR and subsequently sequenced. The screened CPPs for each cell line were identified after four rounds of selection. Among them, two peptides, MAMPGEPRRANVMAHKLEPASLQLR NSCA (CPPK) and MAPQRDTVGGRTTPPSWGPAKAQLRNSCA (CPPL) were selected, and the FITC-labeled peptides were evaluated for their ability to penetrate cells. The screened CPPs were superior to polyarginine (R(11) ), which is widely used as a standard peptide and shows good cell penetration efficiency. Our method can be applied to other target cells for which CPPs have not yet been elucidated. PMID- 22076845 TI - A late-stage intermediate in salinomycin biosynthesis is revealed by specific mutation in the biosynthetic gene cluster. PMID- 22076846 TI - Dihydronaphthyl-based [60]fullerene bisadducts for efficient and stable polymer solar cells. AB - Dihydronaphthyl-based [60]fullerene bisadduct derivative, NC(60)BA, was synthesized at mild temperature in high yield. NC(60)BA not only possesses a LUMO energy level 0.16 eV higher than PC(61)BM but also has amorphous nature that can overcome thermal-driven crystallization. The fabricated P3HT:NC(60)BA-based polymer solar cells exhibit superior photovoltaic performance and thermal stability compared to PC(61)BM-based devices under the same conditions. PMID- 22076847 TI - Consensus treatments for moderate juvenile dermatomyositis: beyond the first two months. Results of the second Childhood Arthritis and Rheumatology Research Alliance consensus conference. AB - OBJECTIVE: To use consensus methods and the considerable expertise contained within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) organization to extend the 3 previously developed treatment plans for moderate juvenile dermatomyositis (DM) to span the full course of treatment. METHODS: A consensus meeting was held in Chicago on April 23-24, 2010, involving 30 pediatric rheumatologists and 4 lay participants. Nominal group technique was used to achieve consensus on treatment plans that represented typical management of moderate juvenile DM. A preconference survey of CARRA, completed by 151 (56%) of 272 members, was used to provide additional guidance to the discussion. RESULTS: Consensus was reached on timing and rate of steroid tapering, duration of steroid therapy, and actions to be taken if patients were unchanged, worsening, or experiencing medication side effects or disease complications. Of particular importance, a single consensus steroid taper was developed. CONCLUSION: We were able to develop consensus treatment plans that describe therapy for moderate juvenile DM throughout the treatment course. These treatment plans can now be used clinically, and data collected prospectively regarding treatment effectiveness and toxicity. This will allow comparison of these treatment plans and facilitate the development of evidence-based treatment recommendations for moderate juvenile DM. PMID- 22076848 TI - Polymer coatings that display specific biological signals while preventing nonspecific interactions. AB - Control over cell-material surface interactions is the key to many new and improved biomedical devices. It can only be achieved if interactions that are mediated by nonspecifically adsorbed serum proteins are minimized and if cells instead respond to specific ligand molecules presented on the surface. Here, we present a simple yet effective surface modification method that allows for the covalent coupling and presentation of specific biological signals on coatings which have significantly reduced nonspecific biointerfacial interactions. To achieve this we synthesized bottle brush type copolymers consisting of poly(ethylene glycol) methyl ether methacrylate and (meth)acrylates providing activated NHS ester groups as well as different spacer lengths between the NHS groups and the polymer backbone. Copolymers containing different molar ratios of these monomers were grafted to amine functionalized polystyrene cell culture substrates, followed by the covalent immobilization of the cyclic peptides cRGDfK and cRADfK using residual NHS groups. Polymers were characterized by GPC and NMR and surface modification steps were analyzed using XPS. The cellular response was evaluated using HeLa cell attachment experiments. The results showed strong correlations between the effectiveness of the control over biointerfacial interactions and the polymer architecture. They also demonstrate that optimized fully synthetic copolymer coatings, which can be applied to a wide range of substrate materials, provide excellent control over biointerfacial interactions. PMID- 22076849 TI - Conjugated polymer-grafted reduced graphene oxide for nonvolatile rewritable memory. PMID- 22076851 TI - [Psychiatry, an attractive career choice?]. PMID- 22076850 TI - Annual change in Friedreich's ataxia evaluated by the Scale for the Assessment and Rating of Ataxia (SARA) is independent of disease severity. AB - BACKGROUND: The objective of the study was to evaluate the sensitivity to change of the Scale for the Assessment and Rating of Ataxia (score, 0-40) in Friedreich's ataxia. METHODS: This was a follow-up study in adult patients with genetically confirmed Friedreich's ataxia evaluated at least twice (minimum interval, 6 months). Participants were outpatients at the Center for Neurogenetics of the Pitie-Salpetriere Hospital in Paris. RESULTS: We included 84 patients; 60% had 3 or more evaluations. The mean score on first assessment was 22.7 +/- 9, and the mean follow-up was 1.84 +/- 1.10 years. The mean increase was 1.36 +/- 2.3 points/year; this variation was not significantly linked to factors known to influence disease severity such as age at onset, disease duration, GAA expansion length, and wheelchair use. CONCLUSIONS: In adult Friedreich's ataxia patients the Scale for the Assessment and Rating of Ataxia can detect annual changes independently of disease severity. In future therapeutic trials no patient stratification is globally required. PMID- 22076852 TI - [Ethnic differences between pre-trial suspected offenders]. AB - BACKGROUND: Black and minority ethnic (BME) patients with a severe psychiatric disorder are compulsory admitted to psychiatric hospitals more often than Dutch native patients. AIM: To describe ethnic differences with regard to (1) the prevalence of psychiatric disorders, (2) the degree to which 'suspects' are considered to be accountable for their actions and (3) recommended treatment for reported pre-trial suspects. METHOD: 14,540 pre-trial reports in the Netherlands between 2000 and 2006 with a known ethnicity were assessed. Dutch native, Western, Turkish, Moroccan, Surinamese, Antillean, and other non-Western defendants were compared with chi-square tests and logistic regression models. RESULTS: Psychotic and behavioural disorders were more prevalent among bme suspects, whereas all other psychiatric disorders occurred less frequently in the BME group. Compared to Dutch native suspects, BME suspects were more often deemed to be fully accountable for their actions. Antillean, Moroccan, Surinamese, and other non-Western suspects were more often recommended for compulsory admission to a psychiatric hospital or received no treatment and much less out-patient treatment. There were no ethnic differences with regard to the frequency with which suspects were recommended for compulsory admission to a penitentiary hospital or with regard to medication. CONCLUSION: Compared to Dutch native suspects, BME suspects are, on one hand, more often deemed accountable for their actions but, on the other hand, are more often recommended for compulsory admission to a psychiatric hospital. PMID- 22076853 TI - [Mania in late life: bipolar disorder as diagnosis by exclusion]. AB - BACKGROUND: The underlying cause of mania in later life can be an early- or late onset bipolar disorder or it can be a mood disorder arising from a physical illness, also known as 'a secondary mania'. Thorough diagnostic tests are needed to differentiate between the two types of mania. AIM: To discuss the epidemiology, presentation, diagnostic considerations and treatment options when a mania develops in later life. METHOD: The literature was studied systematically with the help of PubMed, the Cochrane Library, specialist manuals, Dutch guidelines and references. RESULTS: So far, research into the incidence and prevalence of a mania in later life has been very limited. In making a differential diagnosis of this kind of mania the clinician has to consider not only the possibility of a bipolar disorder, severe depression or psychosis but also the possibility of delirium, dementia or secondary mania. According to some researchers, a mania can be caused by various neurological, systemic and pharmacological factors. Patients should be given somatic screening, including brain imaging. Lithium and antipsychotics are the agents of choice for treating a mania occurring as part of a bipolar disorder as well as for treating a secondary mania. CONCLUSION: Epidemiologic research into late-onset mania is limited. In older patients it is important to identify -or rule out- somatic causes (secondary mania, dementia, delirium). Symptomatic treatment is more or less on the same lines as the treatment for mania in young adults. In cases of secondary mania maintenance treatment is not always necessary, but must be considered if risk factors for bipolar disorder are present. PMID- 22076854 TI - [The Netherlands Association for Psychiatry: 140 years of lurching between differentiation and integration]. AB - BACKGROUND: Over the last 20 years the Netherlands Association for Psychiatry (Nederlandse Vereniging voor Psychiatrie) has undergone fundamental changes, both in its internal functioning and in its relationship to society. The 140th birthday of the Association is a fitting occasion on which to look back on its history. AIM: o give an overview of the Association's importance for psychiatry, psychiatrists and psychiatric care and to summarise the aspects that have continued those that have changed. METHOD: Primary sources (the Association's archives) and additional literature were studied. results: In view of the scholarly and professional heterogeneity of the Association it is amazing that the members have never really split up into factions, the only exception being the neurologists. CONCLUSION: Through out its history the medical identity of the Association has been the most important binding factor. Biopsychosocial generalism was undoubtedly a premise, although, in fact, major changes in emphasis did occur. PMID- 22076855 TI - [Conditional shared confidentiality with regard to the exchange of information between members of a team or network; ethical advice needs to be updated]. AB - BACKGROUND: Care-givers not only work as a team, but increasingly they also participate in networks. This development represents an ethical challenge to the exchange of information and to confidentiality. OBJECTIVE: To revise and update earlier advice formulated by the Ethics Committee for Mental Health Care of the Brothers of Charity in Flanders, in particular concerning the question of whether shared confidentiality can be extended from a team to a network. METHOD: The Ethics Committee applied an appropriate method which combined ethical discussion and literature research. RESULTS: The earlier advice is no longer adequate because of certain practical and theoretical grounds. The Ethics Committee chooses to take a positive view of the developing cooperation between care-givers and networks. Consequently, the committee proposes shared confidentiality, but links this to five conditions: (1) the care-givers should participate in a clearly defined and identifiable team or network, (2) they should have a caring task in common, (3) they should be pledged to confidentiality, (4) they should consult with the patient and obtain his/her informed consent, (5) they should apply 'the filter of relevance'. CONCLUSION: Care-givers can exchange information with members of a team or network, but this should be done on the basis of conditional shared confidentiality. PMID- 22076856 TI - [Parents with severe mental illness. Epidemiological data]. AB - BACKGROUND: It is becoming increasingly clear that people with severe mental illness (SMI) are in need of support with parenting. So far, however, little is known about how many persons fall into this category. AIM: To estimate how many SMI patients aged 18 to 65 are parents with children and how many need help with parenting. METHOD: We based our estimate on epidemiological studies and on official records and data relating to SMI patients for the year 2009. RESULTS: We estimated that 48% of patients with smi had children. The total number of such patients for the year 2009 was 68,000; this figure represents 0.9% of the Dutch population in the 18-64 age-group. CONCLUSION: Health professionals and carers need to be alerted to the fact that almost 50%of the patients with SMI require possibly help in fulfilling their parental role. Potential problems in the parent child relationship need to be registered in greater details so that more adequate care can be provided both at individual level and national level. PMID- 22076857 TI - [Contact with the child and adolescent psychiatric services is determined by cultural and socio-economic differences]. AB - BACKGROUND: In the Netherlands access to mental healthcare is not evenly distributed over ethnic groups. Young persons of non-Dutch origin make only limited use of Dutch child and adolescent psychiatric services. AIM: To investigate to what extent differences in the use of child and adolescent psychiatric services are related to ethnic cultural factors or socio-economic position. METHOD: On the basis of data from the Rotterdam psychiatric case register we calculated the incidence-related risks for different ethnic groups and according to income level. Poisson regression analysis enabled us to take into account differences in the composition of the groups according to age and gender. RESULTS: All ethnic groups have less contact than the native population with the psychiatric services, but there is also an effect of income level, irrespective of ethnicity. In the native population the number of persons seeking assistance from the psychiatric services was found to be higher in lower income categories. CONCLUSION: Access to the child and adolescent psychiatric services is influenced by both ethnic and socio-cultural differences. PMID- 22076858 TI - [Narcolepsy in children with a psychiatric disorder]. AB - Children with a psychiatric disorder often have sleep problems. To interpret these problems correctly one needs to conduct a multimodal investigation at three levels: internal, psychiatric and neurological. On the basis of a case study we discuss the differential diagnostic considerations for narcolepsy and a diagnostic protocol for children. PMID- 22076859 TI - [Reaction on: vitamin D deficiency and psychiatric patients]. PMID- 22076860 TI - Evidence of frontotemporal structural hypoconnectivity in social anxiety disorder: A quantitative fiber tractography study. AB - Investigation of the brain's white matter fiber tracts in social anxiety disorder (SAD) may provide insight into the underlying pathophysiology. Because models of pathological anxiety posit altered frontolimbic interactions, the uncinate fasciculus (UF) connecting (orbito-) frontal and temporal areas including the amygdala is of particular interest. Microstructural alterations in parts of the UF have been reported previously, whereas examination of the UF as discrete fiber tract with regard to more large-scale properties is still lacking. Diffusion tensor imaging was applied in 25 patients with generalized SAD and 25 healthy control subjects matched by age and gender. By means of fiber tractography, the UF was reconstructed for each participant. The inferior fronto-occipital fasciculus (IFOF), originating from the frontal cortex similarly to the UF, was additionally included as control tract. Volume and fractional anisotropy (FA) were compared between the groups for both tracts. Volume of left and right UF was reduced in patients with SAD, reaching statistical significance for the left UF. Bilateral IFOF volume was not different between groups. A similar pattern was observed for FA. Reduced volume of the left UF in SAD fits well into pathophysiological models of anxiety, as it suggests deficient structural connectivity between higher-level control areas in the orbitofrontal cortex and more basal limbic areas like the amygdala. The results point to a specific role of the left UF with regard to altered white matter volume in SAD. However, results should be replicated and functional correlates of altered UF volume be determined in future studies. PMID- 22076861 TI - Evaluating the suitability of planted forests for African forest monkeys: a case study from Kakamega forest, Kenya. AB - As natural forest cover declines, planted forests have come to occupy an increasing percentage of the earth's surface, yet we know little about their suitability as alternative habitat for wildlife. Although some primate species use planted forests, few studies have compared primate populations in natural and nearby planted forests. From March 2006 to July 2010, we conducted line transect surveys and assessed group sizes and compositions in natural and nearby 60-70 year old mixed indigenous planted forest to determine the densities of diurnal primate species (Colobus guereza, Cercopithecus mitis, C. ascanius) in these two forest types at Isecheno, Kakamega Forest, Kenya. Line transect data were analyzed using the Encounter Rate, Whitesides, and Distance sampling methods, which all provided broadly consistent results. We found that all three diurnal primate species occupy both natural and planted forest at Isecheno. However, group densities of the two Cercopithecus species were 42-46% lower in planted than in natural forest. Colobus guereza achieved comparable group densities in the two forest types, although the species is found in smaller groups, and thus at lower (35%) individual density, in planted than in natural forest. Following a logging episode in the planted forest mid-way through our study, Cercopithecus ascanius group densities fell by 60% while C. mitis and Colobus guereza group densities remained stable over the next two years. Overall, our results suggest that while primate species vary in their response to habitat disturbance, planted forest has the potential to contribute to the conservation of some African monkey species. Even for the relatively flexible taxa in our study, however, 60-70 year old mixed indigenous planted forest failed to support densities comparable to those in nearby natural forest. From the perspective of Kakamega's primates, planted forests may supplement natural forest, but are not an adequate replacement for it. PMID- 22076862 TI - Tracheal intubation in an unanticipated difficult airway by advancing a bronchoscope and a tracheal tube introducer through a LMA SupremeTM. PMID- 22076863 TI - Histidine affinity tags affect MSP1(42) structural stability and immunodominance in mice. AB - Inclusion of affinity tags has greatly facilitated process development for protein antigens, primarily for their recovery from complex mixtures. Although generally viewed as supportive of product development, affinity tags may have unintended consequences on protein solubility, susceptibility to aggregation, and immunogenicity. Merozoite surface protein 1 (MSP1), an erythrocytic stage protein of Plasmodium falciparum and a candidate malaria vaccine, was used to evaluate the impact of a metal ion affinity-tag on both protein structure and the induction of immunity. To this end, codon harmonized gene sequences from the P. falciparum MSP1(42) of FVO and 3D7 parasites were cloned and purified with and without a histidine (His) tag. We report on the influence of His-affinity tags on protein expression levels, solubility, secondary structure, thermal denaturation, aggregation and the impact on humoral and cellular immune responses in mice. While the overall immunogenicity induced by His-tagged MSP1(42) proteins is greater, the fine specificity of the humoral and cellular immune responses is altered relative to anti-parasitic antibody activity and the breadth of T-cell responses. Thus, the usefulness of protein tags may be outweighed by their potential impact on structure and function, stressing the need for caution in their use. See accompanying commentary by Randolph DOI: 10.1002/biot.201100459. PMID- 22076864 TI - Robotic stereotactic body radiotherapy in the treatment of sinonasal mucosal melanoma: report of four cases. AB - BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a rare entity originating from melanocytes of the sinonasal mucosa. Postoperative radiotherapy is recommended in all cases to increase local control. However, external radiotherapy is rarely used as a definitive treatment modality. In this report, we present 4 cases of SNMM treated with CyberKnife (Accuray, Sunnyvale, CA). METHODS: All patients were immobilized with a thermoplastic mask. A planning CT scan with 1-mm thickness was obtained, and these images were fused with MRI for the contouring procedure. Multiplan (Accuray) inverse planning software was used for treatment planning. Robotic stereotactic body radiotherapy (SBRT) was delivered with CyberKnife. RESULTS: Median follow-up was 26 months. Three patients had complete response to CyberKnife, and 1 patient had partial response. CONCLUSION: Robotic SBRT seems to be an appealing treatment option for local control. Effective systemic treatment is required to prevent distant metastases. PMID- 22076865 TI - A two-color, self-controlled molecular beacon. AB - Control yourself! A two-color molecular beacon with non-nucleosidic chromophores in a triplex stem is presented. Pyrene and PDI fluorophores act as mutual quenchers by formation of a donor-acceptor complex in the closed form. Hybridization with the target results in two independent fluorescence signals. The two-color read-out provides a "self-control" feature, which helps to eliminate false positive signals in imaging and screening applications. PMID- 22076866 TI - Quantification of protein interaction in living cells by two-photon spectral imaging with fluorescent protein fluorescence resonance energy transfer pair devoid of acceptor bleed-through. AB - Fluorescence resonance energy transfer (FRET) between fluorescent proteins (FPs) is a powerful method to visualize and quantify protein-protein interaction in living cells. Unfortunately, the emission bleed-through of FPs limits the usage of this complex technique. To circumvent undesirable excitation of the acceptor fluorophore, using two-photon excitation, we searched for FRET pairs that show selective excitation of the donor but not of the acceptor fluorescent molecule. We found this property in the fluorescent cyan fluorescent protein (CFP)/yellow fluorescent protein (YFP) and YFP/mCherry FRET pairs and performed two-photon excited FRET spectral imaging to quantify protein interactions on the later pair that shows better spectral discrimination. Applying non-negative matrix factorization to unmix two-photon excited spectral imaging data, we were able to eliminate the donor bleed-through as well as the autofluorescence. As a result, we achieved FRET quantification by means of a single spectral acquisition, making the FRET approach not only easy and straightforward but also less prone to calculation artifacts. As an application of our approach, the intermolecular interaction of amyloid precursor protein and the adaptor protein Fe65 associated with Alzheimer's disease was quantified. We believe that the FRET approach using two-photon and fluorescent YFP/mCherry pair is a promising method to monitor protein interaction in living cells. PMID- 22076867 TI - Following aptamer-ricin specific binding by single molecule recognition and force spectroscopy measurements. AB - Single molecule recognition imaging and dynamic force spectroscopy (DFS) analysis showed strong binding affinity between an aptamer and ricin, which was comparable with antibody-ricin interaction. Molecular simulation showed a ricin binding conformation with aptamers and gave different ricin conformations immobilizing on substrates that were consistent with AFM images. PMID- 22076868 TI - Rates and correlates of sexual activity and impairment among women with systemic sclerosis. AB - OBJECTIVE: To assess 1) the rates of sexual activity and impairment, 2) clinical correlates of sexual activity/impairment, and 3) common sources of pain during and after sex in a large sample of female patients with systemic sclerosis (SSc; scleroderma). METHODS: We performed a cross-sectional multicenter study of female SSc patients from the Canadian Scleroderma Research Group Registry. Patients underwent medical examinations and clinical histories and were asked whether they had engaged in sexual activities with their partner in the past 4 weeks. Sexually active patients completed a 9-item version of the Female Sexual Function Index (FSFI) and items related to problems that may be linked to sexual dysfunction in SSc. Multivariate logistic regressions assessed independent predictors of activity/inactivity and sexual dysfunction. RESULTS: A total of 226 (41%) of 547 patients, including 215 (54%) of the 401 patients currently in relationships, reported having engaged in sexual activities with a partner in the past 4 weeks. Among 165 sexually active patients with complete data for all variables, 102 (62%) had FSFI total scores <=22.5, indicating impaired function. Seventeen percent of the patients were sexually active and not impaired. Independent predictors (P < 0.05) of sexual activity were younger age, fewer gastrointestinal symptoms, and less severe Raynaud's phenomenon symptoms. Sexual impairment was independently associated with older age, higher skin scores, and more severe breathing problems. Vaginal pain was 8 times more likely among women with impairment. CONCLUSION: Research is needed to compare the extent of activity and impairment in SSc compared to women without SSc and to develop interventions to address impaired sexual function in women with SSc. PMID- 22076869 TI - Myrosinase hydrolysates of Brassica oleraceae L. var. italica reduce the risk of colon cancer. AB - By means of liquid chromatography-electrospray ionization (LC-ESI) mass spectrometry two glucosinolates, glucoiberin and 3-hydroxy,4(alpha-L rhamnopyranosyloxy) benzyl glucosinolate, were identified in the aqueous extract of Brassica oleraceae L var. italica. Further, two compounds were isolated after enzymatic hydrolysis of the aqueous extract by myrosinase, one of them was identified as 4-vinyl-3-pyrazolidinone. The second compound (sulphoraphane) 1 isothiocyanate-4-methyl-sulphinyl butane, converted to the most stable form of thiourea (sulphoraphane thiourea). The crude extract (80% alcohol extract) of broccoli florets was examined for cytotoxic activity against different human cancer cell lines, it showed good inhibition of colon cancer (IC(50) 3.88 ug/mL). On the other hand each of the successive extracts (petroleum ether, chloroform, ethyl acetate and ethanol) showed no significant cytotoxic activity. When myrosinase hydrolysate was tested for cytotoxic activity on the colon cancer cell line it showed very high activity - 95% lethality up to 0.78 ug/mL. PMID- 22076870 TI - Prefrontal alterations in Parkinson's disease with levodopa-induced dyskinesia during fMRI motor task. AB - Levodopa-induced dyskinesia represents disabling complication of long-term therapy with dopaminergic drugs in treating Parkinson's disease (PD). Recently, our group demonstrated that PD patients with levodopa-induced dyskinesia were characterized by abnormal volumetric changes in the inferior prefrontal gyrus. In this study, the functional relevance of this structural abnormality was explored using functional magnetic resonance imaging. Ten dyskinetic PD patients and 10 nondyskinetic PD patients were studied in the OFF phase with functional magnetic resonance imaging while performing externally and internally triggered visuomotor tasks. Although neither group demonstrated behavioral differences during execution of motor tasks, magnetic resonance imaging analysis detected significant changes in target cortical regions. In particular, PD patients with levodopa-induced dyskinesia showed significant overactivity in the supplementary motor area and underactivity in the right inferior prefrontal gyrus during execution of both tasks when compared with PD patients without levodopa-induced dyskinesia. Moreover, these prefrontal functional alterations were significantly correlated with Abnormal Involuntary Movement Scale scores. This functional magnetic resonance imaging study together with our previous volumetric findings highlights the role of the prefrontal cortex in the neuronal mechanisms of dyskinesia. PMID- 22076871 TI - Does sleep restore the topology of functional brain networks? AB - Previous studies have shown that healthy anatomical as well as functional brain networks have small-world properties and become less optimal with brain disease. During sleep, the functional brain network becomes more small-world-like. Here we test the hypothesis that the functional brain network during wakefulness becomes less optimal after sleep deprivation (SD). Electroencephalography (EEG) was recorded five times a day after a night of SD and after a night of normal sleep in eight young healthy subjects, both during eyes-closed and eyes-open resting state. Overall synchronization was determined with the synchronization likelihood (SL) and the phase lag index (PLI). From these coupling strength matrices the normalized clustering coefficient C (a measurement of local clustering) and path length L (a measurement of global integration) were computed. Both measures were normalized by dividing them by their corresponding C-s and L-s values of random control networks. SD reduced alpha band C/C-s and L/L-s and theta band C/C-s during eyes-closed resting state. In contrast, SD increased gamma-band C/C-s and L/L-s during eyes-open resting state. Functional relevance of these changes in network properties was suggested by their association with sleep deprivation induced performance deficits on a sustained attention simple reaction time task. The findings indicate that SD results in a more random network of alpha-coupling and a more ordered network of gamma-coupling. The present study shows that SD induces frequency-specific changes in the functional network topology of the brain, supporting the idea that sleep plays a role in the maintenance of an optimal functional network. PMID- 22076872 TI - The influence of induction therapy for kidney transplantation after a non-renal transplant. AB - BACKGROUND AND OBJECTIVES: Non-renal transplant recipients who subsequently develop ESRD and undergo kidney transplantation are medically and immunologically complex due to comorbidities, high cumulative exposure to immunosuppressants, and sensitization to alloantigen from the prior transplant. Although prior non-renal transplant recipients are one of the fastest growing segments of the kidney wait list, minimal data exist to guide the use of antibody induction therapy (IT+) at the time of kidney after lung (KALu), heart (KAH), and liver (KALi) transplant. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study used national registry data to examine IT use and survival after kidney transplantation. Separate multivariate Cox regression models were constructed to assess patient survival for IT+ and IT- KALu (n=232), KAH (n=588), and KALi (n=736) recipients. RESULTS: Use of IT increased during the study period. The percentage of patients considered highly sensitized (panel reactive antibody >=20%) was not statistically significant between IT+ and IT- groups. IT+ was not associated with improvement in 1- and 10-year patient survival for KALu (P=0.20 and P=0.22, respectively) or for KAH (P=0.90 and P=0.14, respectively). However, IT+ among KALi was associated with inferior patient survival at 1 and 10 years (P=0.04 and P=0.02, respectively). CONCLUSIONS: Use of IT for kidney transplantation among prior non-renal transplant recipients may not offer a survival advantage in KALu or KAH. However, due to limited power, these findings should be interpreted cautiously. IT+ was associated with inferior outcomes for KALi. Use of IT should be judicially reconsidered in this complex group of recipients. PMID- 22076873 TI - Venous thromboembolism in patients with membranous nephropathy. AB - BACKGROUND AND OBJECTIVES: The aims of this study were to determine the frequency of venous thromboembolic events in a large cohort of patients with idiopathic membranous nephropathy and to identify predisposing risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied patients with biopsy-proven membranous nephropathy from the Glomerular Disease Collaborative Network (n=412) and the Toronto Glomerulonephritis Registry (n=486) inception cohorts. The cohorts were pooled after establishing similar baseline characteristics (total n=898). Clinically apparent and radiologically confirmed venous thromboembolic events were identified. Potential risk factors were evaluated using multivariable logistic regression models. RESULTS: Sixty-five (7.2%) subjects had at least one venous thromboembolic event, and this rate did not differ significantly between registries. Most venous thromboembolic events occurred within 2 years of first clinical assessment (median time to VTE = 3.8 months). After adjusting for age, sex, proteinuria, and immunosuppressive therapy, hypoalbuminemia at diagnosis was the only independent predictor of a venous thromboembolic event. Each 1.0 g/dl reduction in serum albumin was associated with a 2.13-fold increased risk of VTE. An albumin level <2.8 g/dl was the threshold below which risk for a venous thromboembolic event was greatest. CONCLUSIONS: We conclude that clinically apparent venous thromboembolic events occur in about 7% of patients with membranous nephropathy. Hypoalbuminemia, particularly <2.8 g/dl, is the most significant independent predictor of venous thrombotic risk. PMID- 22076874 TI - Early renal function decline in type 2 diabetes. AB - BACKGROUND AND OBJECTIVES: Early decline in GFR may reflect progressive kidney disease in type 1 diabetes, but its predictive value in type 2 diabetes is uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this longitudinal study, GFR was measured serially over approximately 4.0 years in 195 Pima Indians with type 2 diabetes. Renal function decline (RFD) was defined during this initial period by an average GFR loss >=3.3%/yr, as defined previously in type 1 diabetes. Subsequently, participants were followed for up to 17.8 years to ESRD onset, death, or December 31, 2010, whichever came first. RESULTS: RFD prevalence during the initial period was 32% in 68 participants with normal baseline albuminuria (albumin/creatinine ratio [ACR] < 30 mg/g), 42% in 88 with microalbuminuria (ACR 30 to <300 mg/g), and 74% in 39 with macroalbuminuria (ACR >=300 mg/g; P<0.001). The cumulative incidence of ESRD 10 years after the initial period was 41% in those with RFD and 15% in those without (P<0.001); 41 of the 49 ESRD cases (83.7%) occurred in participants who had or developed macroalbuminuria during the initial period. When adjusted for age, sex, diabetes duration, and hemoglobin A1c, the ESRD hazard rate was 4.78 times (95% confidence interval, 2.39-9.58) as high in those with RFD as in those without; further adjustment for albuminuria attenuated this association (hazard ratio, 1.79; 95% confidence interval, 0.82-3.91). CONCLUSIONS: In type 2 diabetes, loss of GFR often occurs before the onset of macroalbuminuria, but a decline predictive of ESRD is strongly dependent on progression to macroalbuminuria. PMID- 22076876 TI - Adding specialized clinics for remote-dwellers with chronic kidney disease: a cost-utility analysis. AB - BACKGROUND AND OBJECTIVES: This study aimed to determine whether opening a new clinic in a remote region would be a cost-effective means of improving care for remote-dwellers with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study is a cost-utility analysis from a public payer's perspective over a lifetime horizon, using administrative data from a large cohort of adults with stage 3b-4 CKD in Alberta, Canada. The association between the distance from each simulated patient's residence and the practice location of the closest nephrologist and clinical outcomes (quality of care, hospitalization, dialysis, and death) were examined. A Markov 6-month cycle economic decision model was analyzed; estimates of the effect of a new clinic were based on the association between residence location, resource use, and outcomes. Costs are reported in 2009 Canadian dollars. RESULTS: The costs for equipping and operating a clinic for 321 remote-dwelling patients were estimated at $25,000 and $250,000/yr, respectively. The incremental cost-utility ratios (ICURs) ranged from $4000 to $8000/quality-adjusted life-year under most scenarios. However, if reducing distance to nephrologist care does not alter mortality or hospitalization among remote-dwellers, the cost-effectiveness becomes less attractive. All other one way sensitivity analyses had negligible effects on the ICUR. CONCLUSIONS: Given the low costs of equipping and operating new clinics, and the very attractive ICUR relative to other currently funded interventions, establishing new clinics for remote-dwellers could play an important role in efficiently improving outcomes for patients with CKD. High-quality controlled studies are required to confirm this hypothesis. PMID- 22076875 TI - Serum fibroblast growth factor-23 and risk of incident chronic kidney disease in older community-dwelling women. AB - BACKGROUND AND OBJECTIVES: Elevated circulating fibroblast growth factor 23 (FGF23) predicts progression of CKD, but it is unknown whether circulating FGF23 independently predicts incident CKD. This study aimed to determine whether circulating FGF23 predicts incident CKD in community-dwelling women. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examined the relationship of intact serum FGF23, 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D), 25-hydroxyvitamin D (25[OH]D), parathyroid hormone, calcium, and phosphate with prevalent and incident CKD in 701 disabled women, >=65 years of age, from the Women's Health and Aging Study I in Baltimore, Maryland, from 1993 to 1997. Incident CKD was defined as a low estimated GFR (eGFR) <60 ml/min per 1.73 m(2) only, low eGFR <60 ml/min per 1.73 m(2) and a >=25% decline in eGFR from baseline, and an increase in serum creatinine (>=0.4 mg/dl) at follow-up. RESULTS: At baseline, 381 women (54.3%) had stage 3 CKD. Of 307 women without CKD at baseline, 63 (20.5%) developed stage 3 CKD over 24 months of follow-up. After excluding prevalent cases of CKD, FGF23 (per 1 SD increase) was associated with incident stage 3 CKD (hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.06, 2.16; P=0.02), low and declining eGFR (HR, 3.69; 95% CI, 1.68, 8.11; P=0.001), and increase in serum creatinine (HR, 5.35; 95% CI, 1.27, 22.54; P=0.02) in respective multivariable Cox proportional hazards models adjusting for baseline eGFR, age, race, phosphate, 1,25-dihydroxyvitamin D(3), parathyroid hormone, and other potential confounders. CONCLUSIONS: Elevated FGF23 is an independent risk factor for incident CKD in older, disabled, community-dwelling women. PMID- 22076878 TI - Improving ascertainment of sudden cardiac death in patients with end stage renal disease. AB - BACKGROUND AND OBJECTIVES: Data collected by the US Renal Data System (USRDS) identify sudden cardiac death (SCD) as the leading cause of death among hemodialysis patients. However, evidence suggests that clinical events captured on the USRDS death notification form may be inaccurate. A new method for classifying SCD was recently developed to enhance the accuracy of SCD classification. This study examined the performance characteristics of this refined definition using a cohort of hemodialysis patients who experienced a witnessed SCD as the reference standard. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective cohort study of 363 patients who experienced a witnessed SCD in US Gambro (DaVita) outpatient dialysis clinics. Sensitivity of SCD defined by death notification forms and SCD defined using additional administrative sources was compared. Clinical data recorded near time of death were also examined. RESULTS: Existing USRDS death notification forms reported 70.8% of witnessed SCD as "cardiac arrest/cause unknown" or "arrhythmia." The refined definition significantly improved identification to 83.8% of witnessed SCD events (P<0.001). Verified SCD cases that were not identified by either definition were more likely to be reported on the death notification form as death due to myocardial infarction, hyperkalemia, sepsis, malignancy, or unknown cause. CONCLUSIONS: Compared with the death notification form alone, the refined SCD definition significantly improves the sensitivity of reporting of witnessed SCD occurring within outpatient hemodialysis clinics. More accurate reporting of cardiac events by clinicians and refinements to existing death notification forms may further improve recognition and understanding of SCD. PMID- 22076879 TI - Racial differences in the incidence of chronic kidney disease. AB - BACKGROUND AND OBJECTIVES: The incidence of ESRD is higher in African Americans than in whites, despite reports of a similar or lower prevalence of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study compared the incidence of CKD among young African-American and white adults over 20 years of follow-up in the community-based Coronary Artery Risk Development in Young Adults study. Participants included 4119 adults, 18-30 years of age, with an estimated GFR (eGFR) >=60 ml/min per 1.73 m(2) at baseline. Incident CKD was defined as an eGFR <60 ml/min per 1.73 m(2) and a >=25% decline in eGFR at study visits conducted 10, 15, and 20 years after baseline. RESULTS: At baseline, the mean age of African Americans and whites was 24 and 26 years, respectively (P<0.001), and 56% and 53% of participants, respectively, were women (P=0.06). There were 43 incident cases of CKD during follow-up, 29 (1.4%) among African Americans and 14 (0.7%) among whites (P=0.02). The age- and sex-adjusted hazard ratio (HR) for incident CKD comparing African Americans to whites was 2.56 (95% confidence interval [95% CI], 1.35-5.05). After further adjustment for body mass index, systolic BP, fasting plasma glucose, and HDL cholesterol, the HR was 2.51 (95% CI, 1.25-5.05). After multivariable adjustment including albuminuria at year 10, the HR for CKD at year 15 or 20 was 1.12 (95% CI, 0.52-2.41). CONCLUSIONS: In this study, the 20-year CKD incidence was higher among African Americans than whites, a difference that is explained in part by albuminuria. PMID- 22076877 TI - Vascular access sites for acute renal replacement in intensive care units. AB - BACKGROUND AND OBJECTIVES: Several temporary venous catheterizations are sometimes required for acute renal replacement therapy (RRT) in the intensive care unit (ICU). This study compares first and second catheterizations in the femoral and jugular veins in terms of patient safety. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A crossover study from the catheter-dialysis randomized study (Cathedia), which was conducted among 736 critically ill adults requiring RRT, was performed. Catheter insertion complications, catheter-tip colonization, catheter dysfunction and urea reduction ratio (URR) were analyzed considering the crossover and longitudinal designs. RESULTS: This study analyzed 134 patients who underwent two different sites of catheterization, 57 and 77 of whom were initially randomized in the femoral and jugular site, respectively. Using anatomic landmarks, time to insert a femoral catheter was shorter (P=0.01) and more successful (P=0.003) compared with catheterization in the jugular site. Time to catheter-tip colonization at removal was not significantly different between the two sites of insertion (median, 14 days in both groups; hazard ratio, 0.99; 95% confidence interval, 0.61-1.59; P=0.96), as well as time to dysfunction. URRs were analyzed from 395 dialysis sessions (n=48 patients). No significant difference (P=0.49) in mean URR was detected between sessions performed through femoral (n=213; 50.9%) and jugular (n=182; 49.5%) dialysis catheters. CONCLUSIONS: These results validate prior results of this study group and extend external validity to the second catheter used for RRT in the ICU. Femoral and internal jugular acute vascular access sites are both acceptable for RRT therapy in the ICU. PMID- 22076880 TI - Predictors of sudden cardiac death: a competing risk approach in the hemodialysis study. AB - BACKGROUND AND OBJECTIVES: There are few data on risk factors for sudden cardiac death (SCD) in patients undergoing hemodialysis (HD). The study objective was to identify predictors associated with various causes of death in the Hemodialysis (HEMO) Study and to develop a prediction model for SCD using a competing risk approach. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this analysis of 1745 HEMO participants, all-cause mortality was classified as SCD, non-SCD, and noncardiac death. Predictors for each cause of death were evaluated using cause specific Cox proportional hazards models, and a competing risk approach was used to calculate absolute risk predictions for SCD. RESULTS: During a median follow up of 2.5 years, 808 patients died. Rates of SCD, non-SCD, and noncardiac death were 22%, 17%, and 61%, respectively. Predictors of various causes of death differ somewhat in HD patients. Age, diabetes, peripheral vascular disease, ischemic heart disease, serum creatinine, and alkaline phosphatase were independent predictors of SCD. The 3-year C-statistic for SCD was 0.75 (95% confidence interval, 0.70-0.79), and calibration was good (chi(2)=1.1; P=0.89). At years 3 and 5 of follow-up, the standard Cox model overestimated the risk for SCD as compared with the competing risk approach on the relative scale by 25% and 46%, respectively, and on the absolute scale by 2% and 6%, respectively. CONCLUSIONS: Predictors of various causes of death differ in HD patients. The proposed prediction model for SCD accounts for competing causes of death. External validation of this model is required. PMID- 22076882 TI - Modeling depression in adult female cynomolgus monkeys (Macaca fascicularis). AB - Depressive disorders are prevalent, costly, and poorly understood. Male rodents in stress paradigms are most commonly used as animal models, despite the two-fold increased prevalence of depression in women and sex differences in response to stress. Although these models have provided valuable insights, new models are needed to move the field forward. Social stress-associated behavioral depression in adult female cynomolgus macaques closely resembles human depression in physiological, neurobiological, and behavioral characteristics, including reduced body mass, hypothalamic-pituitary-adrenal axis perturbations, autonomic dysfunction, increased cardiovascular disease risk, reduced hippocampal volume, altered serotonergic function, decreased activity levels, and increased mortality. In addition, behaviorally depressed monkeys also have low ovarian steroid concentrations, even though they continue to have menstrual cycles. Although this type of ovarian dysfunction has not been reported in depressed women and is difficult to identify, it may be the key to understanding the high prevalence of depression in women. Depressive behavior in female cynomolgus monkeys is naturally occurring and not induced by experimental manipulation. Different social environmental challenges, including isolation vs. subordination, may elicit the depression-like response in some animals and not others. Similarly, social subordination is stressful and depressive behavior is more common in socially subordinate monkeys. Yet, not all subordinates exhibit behavioral depression, suggesting individual differences in sensitivity to specific environmental stressors and enhanced risk of behavioral depression in some individuals. The behavior and neurobiology of subordinates is distinctly different than that of behaviorally depressed monkeys, which affords the opportunity to differentiate between stressed and depressed states. Thus, behaviorally depressed monkeys exhibit numerous physiological, neurobiological, and behavioral characteristics same as those of depressed human beings. The nonhuman primate model represents a new animal model of depression with great promise for furthering our understanding of this prevalent and debilitating disease and identifying novel therapeutic targets. PMID- 22076881 TI - FDG PET in the management of patients with adrenal masses and adrenocortical carcinoma. AB - Adrenocortical carcinoma (ACC) is a rare tumor with aggressive behavior, high recurrence rate, and rapid evolution. Surgery is the only curative modality, while systemic treatments such as mitotane and chemotherapy associated to locoregional therapeutic tools remain as palliative options. Imaging has an important role in the management of patients with ACC both at diagnosis and during follow-up. First, it is necessary to characterize undetermined adrenal masses, selecting patients for surgery. Then, in case of malignancy, it is mandatory to assess disease extension, to detect early relapse during follow-up, and to evaluate treatment response. Computed tomography scan and magnetic resonance imaging are actually the most used techniques for these intents as they are widely available in clinical practice. (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) is routinely used for other malignancies and, on the basis of published data, is also becoming a promising tool in the management of ACC. Not only is it a diagnostic tool complementary to morphological imaging in the characterization of adrenal masses and in tumoral lesions detection, but it can be also useful to evaluate tumor response to treatment. New tracers and indications for the clinical use of FDG PET in this specific disease still have to be evaluated to assess its role in clinical practice. PMID- 22076883 TI - High-affinity, selective sigma ligands of the 1,2,3,4-tetrahydro-1,4' silaspiro[naphthalene-1,4'-piperidine] type: syntheses, structures, and pharmacological properties. AB - The 1'-organyl-1,2,3,4-tetrahydrospiro[naphthalene-1,4'-piperidine] derivatives 1 a-4 a [for which organyl=benzyl (1 a), 4-methoxybenzyl (2 a), 2-phenylethyl (3 a), or 3-methylbut-2-enyl (4 a)] are high-affinity, selective sigma1 ligands. The corresponding sila-analogues 1 b-4 b (replacement of the carbon spirocenter with a silicon atom) were synthesized in multistep syntheses, starting from dichlorodivinylsilane, and were isolated as the hydrochlorides 1 b?HCl-4 b?HCl. Compounds 1 a?HCl-4 a?HCl and 1 b?HCl-4 b?HCl were structurally characterized by NMR spectroscopy (1H, 13C, 29Si) in solution, and the C/Si analogues 3 a?HCl and 3 b?HCl were studied by single-crystal X-ray diffraction. These structural investigations were complemented by computational studies. The sigma1 and sigma2 receptor affinities of the C/Si pairs 1 a/1 b-4 a/4 b were studied with radioligand binding assays. The sigma1 receptor affinity of the silicon compounds 1 b-4 b is slightly higher than that of the corresponding carbon analogues 1 a-4 a. Because affinity for the sigma2 receptor is decreased by the C/Si exchange, the sigma1/sigma2 selectivity of the silicon compounds is considerably improved, indicating that the C->Si switch strategy is a powerful tool for modulating both pharmacological potency and selectivity. PMID- 22076884 TI - Ischemic pancolitis: recognizing a rare form of acute ischemic colitis. PMID- 22076885 TI - Duplication of gallbladder. PMID- 22076886 TI - Bullous dermatosis of hemodialysis: pseudoporphyria. PMID- 22076887 TI - Primary splenic lymphoma. PMID- 22076888 TI - [Fever and bilateral cavitation: pulmonary infarction]. PMID- 22076889 TI - [Primary colonic clear cell adenocarcinoma]. PMID- 22076890 TI - Annular pancreas in adults. PMID- 22076891 TI - [Endometrial adenocarcinoma in young woman]. PMID- 22076892 TI - [Evolution of a refractory cytopenia with multilineage dysplasia and ring sideroblasts to chronic myelomonocytic leukemia]. PMID- 22076893 TI - [Clinical characteristics of Rett Syndrome]. AB - BACKGROUND: Rett Syndrome is a neurodevelopmental disorder, one of the least commonly occurring autism spectrum disorders (ASD),affecting mainly females. AIM: To describe features and molecular specificities of Rett syndrome. METHODS: To identify articles for this review, a Pubmed search was conducted using the following keywords: Rett syndrome, regression,mutation, stereotypes. RESULTS: This syndrome is characterized by cognitive impairment,communication dysfunction, stereotypic movement disorder, and growth failure. It is generally caused by mutations in the MECP2 gene. Rett Syndrome has a prevalence ranging from 10-20 000 females. Specific treatment is not available, but patients need a careful planning for long-term care, with multidisciplinary approaches. PMID- 22076894 TI - [N-acetylcysteine in septic shock]. AB - AIM: To focus on the various studies evaluating the effects of Nacetylcysteine in septic shock METHODS: Main references obtained from the medical database Medline using the keywords: N-acetylcysteine; septic shock, free radicals. RESULTS: Septic shock remains the leading cause of mortality in intensive care units. The progressive knowledge of the pathophysiology of septic shock, underline the production of free radicals and their cellular and microcirculatory effects. The Nacetylcysteine used mainly in paracetamol poisoning, has properties to control free radicals. The explosion of free radicals in septic shock has led to multiple studies assessing the role of N-acetylcysteine as an anti radical, and for its anti inflammatory action. CONCLUSION: NAC seems to play an important role in septic shock to control free radicals and the inflammatory response. But these results remain contradictory. Some larger and more standardized studies should allow to evaluate the actual effects of NAC in septic shock. PMID- 22076895 TI - [The causes of death of the women of childbearing age at the hospitals of Sfax]. AB - AIM: To study the principal causes of death of the women dead at an age ranging between 15 and 49 years old and having been hospitalized in a public medical structures of the gouvernorat of Sfax. METHODS: Retrospective study concerning all the included deaths between 1999 and 2007. RESULTS: The study was related to 728 deaths, which correspond to an average of 80.88 deaths FAR per year. Public highway accidents were the major cause of death (83 cases, 11.4 % of the causes of death) followed by the burns (37 cases, 5%) and the cerebral vascular accidents (31 cases, 4.25%). The classification of the causes of death according to groups of pathologies showed the prevalence of the cardio- vascular diseases (18.7%), the external causes of death (18.2%), cancers (11.6%) and the causes related to the pregnancy and the childbirth (8.5%). The maternal death rate was of 56.91 per 100000. The cause of maternal death was directly related to the pregnancy in 67.74 % of the cases. The immediate causes were prevailed by the hemorrhagic causes (27.5%). The death was avoidable in 48.83 % of the cases and the failures were related to the woman in 60% of the cases. CONCLUSION: The prevention of new practices of life (female nicotinism, obesity, bad food habits, lack of vigilance in traffic) and a better practice of the primary and secondary prevention in medicine could decrease the premature death rates in Tunisia. PMID- 22076896 TI - [Survival in patients with gastric lymphoma]. AB - BACKGROUND: Mucosa-associated lymphoid tissue lymphoma is a histological type of marginal zone non-Hodgkin's lymphoma. Its clinical features and prognosis have seldom been reported because of its indolent clinical course. AIM: To establish prognostic factors that should be considered for the staging and management of this disease. METHODS: Clinical data of 40 pathologically confirmed gastric lymphoma patients, treated during a period of 13 years, were analyzed. RESULTS: Of the 40 patients, 65% had stage IE - II1E disease and 35% had stage II2E - IV disease. A total of 18 patients received surgeries.Eighteen patients had chemotherapy and 10 patients had Helicobacter Pylori eradication therapy. The complete remission rate after treatment was 50%. The patients were followed up for a median of 26.75 months. The 5-year overall survival rate was 70%. Early stage at presentation, surgery, normal lactic dehydrogenase (LDH) levels and Helicobacter Pylori infection were associated with longer survival in univariate analysis. CONCLUSION: This study suggested that surgery might be an important factor predicting the long-term survival of patients with primary gastric lymphoma. Patients with poor prognostic factors should be treated more aggressively. PMID- 22076897 TI - Community-acquired methicillin-resistant Staphylococcus aureus infections requiring admission to a Tunisian pediatric intensive care unit. AB - BACKGROUND: There is limited literature describing severe community acquired methicillin-resistant S aureus (CA-MRSA) in children admitted to an intensive care unit. AIM: To review clinical features and outcome of children admitted in a Tunisian pediatric intensive care with CA-MRSA. METHODS: Retrospective chart review of patients coded for CAMRSA over 10 years. RESULTS: There were 14 (0.32% of all admissions) patients identified with severe CA-MRSA. The median age was 3 months (range,0.5-156 months). All patients had pulmonary involvement. Six children (42.8%) developed septic shock. Two (14.3%) patients had multifocal infection with deep venous thrombosis. Two (14.3%) patients died. CONCLUSION: Severe CA-MRSA pneumonia dominated presentation. The mortality of CA-MRSA infection in our series is lower than reported in the literature. PMID- 22076898 TI - [Obstetrical prognosis following ligation of hypogastric arteries]. AB - BACKGROUND: Ligation of hypogastric arteries is a conservative surgical treatment in cases of postpartum hemorrhage. AIM: To study the fertility and pregnancies outcome in women who required hypogastric artery ligation for severe post-partum haemorrhage in our hospital. METHODS: The fertility and pregnancy outcome parameters were retrieved from medical files and telephone interviews RESULTS: 34 patients required hypogastric ligation on this period. 39 pregnancies were observed with 30 term deliveries, 1 ectopic pregnancies and 8 miscarriages. Two patients had infertility and pregnancy was obtained in less than 10 months most once desired.Pregnancy outcome was normal. 73,3% of deliveries were by caesarean. CONCLUSION: Hypogastric artery ligation for post-partum haemorrhage is not responsible for secondary infertility. Following pregnancies do not suffer complications from the ligation. PMID- 22076899 TI - [Epidemiology of domestic accidents of young children in Tunisia: impact of the training of health professionals on data collection quality]. AB - BACKGROUND: In Tunisia, several studies on domestic injuries have been carried out on children attending care facilities. Nevertheless,there is a lack of data on incidence and kinds of child domestic injuries amongst general population because of absence of a reliable data collect system. AIM: To estimate the incidence and kinds of domestic injuries through a prospective survey "here there" within two cohorts of young children attending two mother and child protection centers (MCPC) in Tunis during the three first years of their life and to analyze the importance of health professional training in improving data collect. METHODS: A prospective study "here-there" was carried out on two cohorts of children in two mother and child protection centers (MCPC) between January 2007 and December 2009. Only children aged less than 3 months at their first contact with the centers were included and followed up until age of 3 years. In the MCPC2 (cohort2), health personnel have been trained on data collection importance related to child domestic accident and asked to monitor accidents by calling parents while a phone line got available for this aim. In the MCPC1, health personnel was asked to work as they used to do and to collect data on child domestic injuries when children attend the center. RESULTS: 192/435 domestic accidents were recorded within cohort 2 vs only 1/686 within cohort 1. Annual incidence rate was 14.7% for the cohort 2. The kinds of accidents were: falls 78.2% (falls from high plans 84.6%), injuries15.1% (injury by cutting things 58.6%),burns 5.7% (burns by hot liquid 54.5%), intoxications 1%. In terms of damages, we recorded 4 cases of broken bones (thighbone, elbow,handwrist), stitches in 11 cases, broken teeth in 3 cases and nail pulled out in one case. No death was recorded. Training impact on accident prevention was not studied. CONCLUSION: Child domestic accidents are relatively frequent. Health personnel training allows to improve data. The kinds of recorded accidents indicate the need to educate parents on best practices towards strengthening prevention. PMID- 22076900 TI - [Handling the cases of school failure in an educational institute in Zaghouan]. AB - AIM: To assess the main reasons for the school failure in a school in Zaghouan, how to handle these issues, to evaluate the work of the school social office. METHODS: A retrospective study included 86 failure cases in a school in Zaghouan, handled by the school social office for three years (2004 - 2007). He have detected the principals causes of school failure, detected by the educational staff or by the listening office. RESULTS: The causes of failure are mainly social (46%) as family problems and low income. These families received financial aids and free treatment cards. Discussions have been made with the parents in order to make them more conscious. The pedagogical reasons (28%) however are usually relationship' problems between the student and his teacher or the student and the administration, the three subjects were informed so that attitudes could be changed in the purpose of helping the student. Twelve students (14%) have a psychological case, depression and over worrying, led in some cases to addiction.These cases were diagnosed and transferred to specialized clinics.Sense and chronic diseases (12%), are considered as health reasons for school failure and caused several absences in the school. The school physicist took care of these cases by handling them medical guidance cards while observing the diagnose progress. As school results, 56 cases turned satisfaisant which is 65 % of all cases. CONCLUSION: The school failure became a priority of the "School Health" institute. That puss to create the school social program, his aim is protecting the students from all dangers, early school leaving and social disintegration, and delinquency. Thus, all parts must be responsible for the school failure, teachers, parents, students,psychiatrists and physicists, as well as introducing the social school work and listening offices and missions to the parents, students and teachers in order to guarantee the success of the operations. PMID- 22076901 TI - [Effectiveness of acupuncture in treating schizophrenia: a clinical randomized trial of 31 patients]. AB - BACKGROUND: Acupuncture is one of the most popular types of complementary/alternative medicine in the world. It is sometimes used as a treatment for schizophrenia mainly in China. AIM: To assess the contribution of acupuncture in the treatment of patients treated for schizophrenia in Tunisian population. METHODS: Our study is a clinical randomized trial about 31 hospitalized patients with schizophrenia or schizo-affectif disorder (DSM IV). They were evaluated by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) the first and 23nd day of the study. Manual acupuncture was used for 10 sessions at the rate of three sessions per week. All patients were under drug therapy. Among them, 15 were treated by acupuncture and 16 by sham acupuncture. RESULTS: Scores of the PANSS, SAPS and SANS were similar in the two groups at the end of the study. CONCLUSION: Our study did not provide any evidence for the effectiveness of acupuncture in treating schizophrenic symptoms. PMID- 22076902 TI - NY-ESO-1 expression and immunogenicity in prostate cancer patients. AB - BACKGROUND: Prostate cancer is the second leading cause of men cancer-related death. Cancer immunotherapy has been investigated as a treatment which might be instituted at the point of detection of androgen-independent metastatic disease. AIM: to investigate the expression and humoral response against NYESO-1 in patients with prostate cancer (PC) and to analyze the relationship between expression of NY-ESO-1 and clinicopathological features. METHODS: NY-ESO-1 mRNA in surgically resected PC and benign prostatic hyperplasia (BPH) were examined by reverse transcriptionpolymerase chain reaction. The antibody response to NY-ESO-1 was examined by enzyme-linked Elisa assay using recombinant NYESO-1 protein. RESULTS: NY-ESO-1 mRNA was detected in 9 of 23 (39%) PC patients. Antibodies against NY-ESO-1 protein were detected in 12 of 23 (52%) sera of PC patients and in 5 of 9 (55%) of NY-ESO-1 expressing tumors. However, no mRNA copy or NY-ESO-1 antibodies were detected in all BPH patients tested. CONCLUSION: The present study has demonstrated the expression of NY-ESO-1mRNA in prostate Cancer patients and NY-ESO-1 antibody production. Our data suggest that NY-ESO-1 could be used as a tumor marker and constitute a good candidate for vaccine-based immunotherapy for hormonal resistant prostate cancer patients. PMID- 22076903 TI - Venous thromboembolism risk and prophylaxis in the acute hospital care setting results of the Endorse study in Tunisia. AB - BACKGROUND: There are not information about the risk of venous thromboembolism (VTE) and its prophylaxis in Tunisia. AIM: To report the Tunisian results of a multinational crosssectional study, designed to assess the prevalence of VTE risk in the acute hospital care setting and to determine the proportion of at risk patients who receive effective prophylaxis. METHODS: All hospital inpatients aged 40 years or over admitted to a medical ward or these aged 18 years or over admitted to surgical ward, in 5 Tunisian hospitals were assessed for risk of VTE on the basis of hospital chart review. The 2004 American College of chest physicians (ACCP) evidence based consensus guidelines were used to assess VTE risk and to determine whether patients were received recommended prophylaxis. RESULTS: 885 were enrolled, 212 (24%) were surgical and 673 (76%) were medical. 408 (44, 9%) judged to be at risk, 95 (44, 8%) are surgical and 313 (46, 5%) are medical. LWMH are the most used. Mechanical prophylaxis was never used. CONCLUSION: The percentage of at risk patient in Tunisia is comparable to these of other countries. The majority of at risk patient are medical. The prophylaxis was under used. Hospital strategies to assess patient VTE risk and implementation of prophylaxis protocols are needed. PMID- 22076904 TI - Sister Mary Joseph's nodule showing adenocarcinoma of pancreas. PMID- 22076905 TI - [Bellini renal cell carcinoma : diagnosis and treatment. A report of 7 cases]. AB - BACKGROUND: The Bellini collecting duct carcinoma (CDC) is a very rare form of renal cell carcinoma (1%) associated with an extremely poor prognosis. AIM: To study clinical and radiological characteristics of CDC. METHODS: From 1993 to 2002, 7 patients with CDC were treated at our institution. The diagnosis of CDC was made by a nephrectomy specimen in all cases. Demographic, clinical, pathological and survival data were gathered. RESULTS: They were five men and two women with an average age of 63 years. Lumbar pain and hematuria were the main symptoms. At presentation 2 T1N0M0, 1 T2N0M0, 1 T3N0M0, 1 T3N+M0 and 2 T4N+M+ tumors were seen. All patients underwent a radical nephrectomy. The two patients who had TNM stage I disease survived without evidence of disease at 5 years and 11 years respectively. Patients with a T4N+M+ tumor experienced rapid progression and died respectively at 3 and 5 months after nephretomy. The 3 other patients with T3N+M0, T3N0M0 and T2N0M0 disease; respectively; progressed rapidly and were lost to follow-up after one year. CONCLUSION: CDC is an aggressive variety of kidney neoplasm that is often associated with nodal and visceral metastases at presentation.It is associated with poor prognosis. For the majority of patients surgical treatment will not result in a cure. Early detection may be the best method for prolonging patient survival. PMID- 22076906 TI - Aberrant expression of CD133 and musashi-1 in preneoplastic and neoplastic human oral squamous epithelium and their correlation with clinicopathological factors. AB - BACKGROUND: The present study focuses on the expression pattern of the stem cell markers CD133 and Musashi-1 in precancerous and cancerous tissues of oral epithelium. The study also aims to investigate the correlation of CD133 and Musashi-1 expression with clinicopathological factors. METHODS: Immunohistochemical analysis was done to investigate the expression pattern of CD133 and Musashi-1, whereas, the coexpression of CD133 and Musashi-1 was studied using immunofluorescence analysis. RESULTS: A gradual increase in the expression of CD133 and Musashi-1 was observed from normal to dysplasia to carcinoma. In addition, the expression of CD133 and Musashi-1 shows significant difference between the stages and histological types of oral carcinoma. Interestingly, coexpression of CD133 and Musashi-1 was observed in oral carcinoma and CAL27 cells. CONCLUSIONS: A gradual increase in the expression of CD133 and Musashi-1 from normal to dysplasia to carcinoma suggests the possible involvement of these 2 proteins in oral carcinogenesis. The overexpression of CD133 and Musashi-1 in advanced stages and also in poorly differentiated tumors reveals their relationship with invasion and differentiation status of oral carcinoma cells. Moreover, the significant positive correlation between CD133 and Musashi-1 expression suggests that they might have a functional relationship in oral carcinoma cells, which needs further investigation. PMID- 22076907 TI - Triazole, benzotriazole, and naphthotriazole as copper corrosion inhibitors: I. Molecular electronic and adsorption properties. AB - The gas-phase adsorption of 1,2,3-triazole, benzotriazole, and naphthotriazole considered as corrosion inhibitors-on copper surfaces was studied and characterized using density functional theory (DFT) calculations. We find that the molecule-surface bond strength increases with increasing molecular size, thus following the sequence: triazole 0.05). PMID- 22076912 TI - Do levodopa treatments modify the morphology of the parkinsonian brain? PMID- 22076913 TI - Acute kidney injury during leukocyte engraftment after autologous stem cell transplantation in patients with light-chain amyloidosis. AB - Engraftment syndrome (ES) is a complication of hematopoietic stem cell transplantation characterized by fever, rash, and non-cardiogenic pulmonary edema. Acute kidney injury (AKI) has been recognized but is considered a minor criterion in one and excluded another definition of ES. We have noted a high incidence of AKI in patients with immunoglobulin light-chain amyloidosis (AL) undergoing autologous stem cell transplant (ASCT) around the time of leukocyte engraftment. This study was conducted to further investigate the relationship between AKI and ES. Data were collected from 377 AL patients who underwent ASCT from 7/1997 to 10/2009. Patients who experienced an elevation of serum creatinine >0.5 mg/dL within 4 days of leukocyte engraftment and anyone who presented with signs associated with ES regardless of renal manifestations were included. Forty one patients met criteria. Twelve were excluded for positive cultures (10), acute interstitial nephritis (1), and acute cellular rejection (1). In addition to AKI (93.1%), patients also exhibit fever (82.7%), hypotension (51.7%), rash (48.2%), edema (93.1%), diarrhea (69.0%), conjunctival hemorrhage (31.0%), pulmonary edema (31.0%), pulmonary hemorrhage (13.8%), and transient encephalopathy (17.2%). Patient with pulmonary involvement were more likely to require dialysis but was not statistically significant. AKI was very common during leukocyte engraftment in AL patients. While infectious etiology accounted for some of the AKI, most appeared to be associated with ES. After infection is ruled out, ES should be considered in the differential diagnosis when evaluating AKI in this population. PMID- 22076914 TI - Laser tissue welding analyzed using fluorescence, Stokes shift spectroscopy, and Huang-Rhys parameter. AB - Near infrared (NIR) continuous wave laser radiation at the 1,450 nm wavelength was used to weld porcine aorta and skin samples via the absorption of combitional vibrational modes of native water in the tissues. The fluorescence spectra were measured from the key native molecules of welded and non-welded tissues at specific excitation and emission wavelengths from collagen, elastin, and tryptophan. The changes in the fluorescence intensities and differences in Stokes shift (Deltanu(ss) ) of key native fluorophores were measured to differentiate the Huang-Rhys parameter values (S) of the chromophores. The strength of coupling depends on the local electron-vibration intra-tissue molecular environment and the amount of polar solvent water surrounding the net charges on collagen, elastin, and tryptophan. The S values for both non-welded and welded tissues were almost the same and less than 3, suggesting minimal changes in the local molecular environment as a result of welding. PMID- 22076915 TI - In vitro models. AB - The current resurgence of interest in the cancer stem cell (CSC) hypothesis as possibly providing a unifying theory of cancer biology is fueled by the growing body of work on normal adult tissue stem cells and the promise that CSC may hold the key to one of the central problems of clinical oncology: tumor recurrence. Many studies suggest that the microenvironment plays a role, perhaps a seminal one, in cancer development and progression. In addition, the possibility that the stem cell-like component of tumors is capable of rapid and reversible changes of phenotype raises questions concerning studies with these populations and the application of what we learn to the clinical situation. These types of questions are extremely difficult to study using in vivo models or freshly isolated cells. Established cell lines grown in defined conditions provide important model systems for these studies. There are three types of in vitro models for CSCs: (a) selected subpopulations of existing tumor lines (derived from serum-containing medium; (b) creation of lines from tumor or normal cells by genetic manipulation; or (c) direct in vitro selection of CSC from tumors or sorted tumor cells using defined serum-free conditions. We review the problems associated with creating and maintaining in vitro cultures of CSCs and the progress to date on the establishment of these important models. PMID- 22076916 TI - Functionalized boranes for hydrogen storage. AB - Using density functional theory, the generalized gradient approximation for the exchange-correlation potential and Moller-Plesset perturbation theory we study the hydrogen uptake of Li- and Mg-doped boranes. Specifically, we calculate the structures and binding energies of hydrogen molecules sequentially attached to LiB(6)H(7), LiB(12)H(13), Li(2)B(6)H(6), Li(2)B(12)H(12), MgB(6)H(6), and MgB(12)H(12). Up to three H(2) molecules can be bound quasi-molecularly to each of the metal cations with binding energies per H(2) molecule ranging between 0.07 eV and 0.27 eV. The corresponding gravimetric densities lie in the range of 3.49 to 12 wt %, not counting the H atoms bound chemically to the B atoms. PMID- 22076917 TI - Impact of comorbidity on therapeutic decision-making in head and neck cancer: audit from a comprehensive cancer center in India. AB - BACKGROUND: Head and neck cancer has increased incidence of comorbidity due to tobacco and alcohol use. METHODS: Two hundred consecutive patients were included in this cross-sectional study. Data on clinico-demographic characteristics and comorbidity was extracted from case records. Comorbidity was assessed with Adult Comorbidity Evaluation 27 (ACE-27) and Charlson Comorbidity Index (CCI). Change in therapeutic decision-making from institutional evidence-based guidelines was classified as low, medium, or high-impact. RESULTS: Of 200 patients, 68(34%) had comorbidity while 15 had multimorbidity. No change in therapeutic decision-making was seen in 139 patients (69.5%), 61patients (30.5%) had change from institutional evidence-based guidelines. There was strong positive correlation (Spearman's correlation coefficient = 0.80; p < .001) between ACE-27 and change in therapeutic decision-making. For CCI, there was moderate positive correlation (Spearman's correlation coefficient = 0.50; p < .001). CONCLUSION: Comorbidity in patients with head and neck cancer can influence therapeutic decision-making. Prospective longitudinal rigorous collection of comorbidity data is warranted for correlation with outcomes. ACE-27 may be a clinically more meaningful tool for comorbidity assessment. PMID- 22076918 TI - Lectin-like oxidized low-density lipoprotein receptor 1 signal is a potent biomarker and therapeutic target for human rheumatoid arthritis. AB - OBJECTIVE: To determine whether lectin-like oxidized low-density lipoprotein (ox LDL) receptor 1 (LOX-1) and the soluble form of LOX-1 (sLOX-1) are novel target molecules for the diagnosis and treatment of rheumatoid arthritis (RA). METHODS: Expression of ox-LDL and LOX-1 proteins in human RA synovium was evaluated by immunohistochemistry. Human RA fibroblast-like synoviocytes (FLS) were assessed for ox-LDL-induced expression of LOX-1 and ox-LDL-induced production of matrix metalloproteinase 1 (MMP-1) and MMP-3. Levels of sLOX-1 in the plasma and synovial fluid of patients with RA, compared with patients with osteoarthritis (OA), were determined by a specific chemiluminescence enzyme-linked immunoassay. In animal experiments, ox-LDL was injected into the knee joints of mice, with or without an anti-LOX-1 neutralizing antibody or sLOX-1, and the severity of arthritis was analyzed by histology and immunohistochemistry. RESULTS: Oxidized LDL and LOX-1 proteins were detected in the RA synovial tissue. Levels of MMP-1 and MMP-3 were enhanced by stimulation of RA FLS with ox-LDL, and the production of both MMPs was inhibited by blockade of the ox-LDL-LOX-1 interaction with the anti-LOX-1 neutralizing antibody or sLOX-1. Levels of sLOX-1 in the plasma and synovial fluid of RA patients were significantly higher than those in OA patients and healthy controls and were positively correlated with inflammation markers and the extent of RA disease activity. In the knees of mice, blockade of the ox-LDL LOX-1 interaction suppressed arthritic changes and reduced the expression of MMP 3 induced by ox-LDL. CONCLUSION: These findings strongly indicate that sLOX-1 is a novel biomarker that may be useful for the diagnosis of RA and for the evaluation of disease activity in RA. Furthermore, the results suggest that LOX-1 may be a potent therapeutic target for RA. PMID- 22076919 TI - A novel flow cytometric protocol for assessment of yeast cell adhesion. AB - Microbial adhesion is a field of recognized relevance and, as such, an impressive array of tools has been developed to understand its molecular mechanisms and ultimately for its quantification. Some of the major limitations found within these methodologies concern the incubation time, the small number of cells analyzed, and the operator's subjectivity. To overcome these aspects, we have developed a quantitative method to measure yeast cells' adhesion through flow cytometry. In this methodology, a suspension of yeast cells is mixed with green fluorescent polystyrene microspheres (uncoated or coated with host proteins). Within 2 h, an adhesion profile is obtained based on two parameters: percentage and cells-microsphere population's distribution pattern. This flow cytometry protocol represents a useful tool to quantify yeast adhesion to different substrata in a large scale, providing manifold data in a speedy and informative manner. PMID- 22076920 TI - MK615, a Prunus mume Steb. Et Zucc ('Ume') extract, attenuates the growth of A375 melanoma cells by inhibiting the ERK1/2-Id-1 pathway. AB - The Japanese apricot, a commonly consumed food called 'Ume' in Japan, has been used for a traditional Japanese medicine for centuries. MK615, an extract of compounds from 'Ume', has strong antitumorigenic and antiinflammatory effects including the induction of apoptosis and autophagy, and inhibition of cytokine production mediated via the inhibition of MAPKs signaling including ERK-1/2, JNK and p38MAPK. The inhibitor of DNA binding 1 (Id-1), a basic helix-loop-helix (bHLH) transcription factor family, is essential for DNA binding and the transcriptional regulation of various proteins that play important roles in the development, progression and invasion of tumors. In melanoma, Id-1 is constitutively expressed in the late and early stages, suggesting it as a therapeutic target in patients with melanoma. This study reports that MK615 profoundly reduced both the mRNA- and protein expression levels of Id-1 and inhibited cell growth in A375 melanoma cells. MK615 markedly inhibited the phosphorylation of ERK1/2, which is associated with Id-1 protein expression in A375 cells. Id-1-specific RNAi induced the death of A375 cells. Moreover, the expression of Bcl-2 was decreased by both MK615 and Id-1-specific RNAi in A375 cells. The results suggest that MK615 is a potential therapeutic agent for treating malignant melanoma. PMID- 22076921 TI - Secondary-structure analysis of alcohol-denatured proteins by vacuum-ultraviolet circular dichroism spectroscopy. AB - To elucidate the structural characteristics of alcohol-denatured proteins, we measured the vacuum-ultraviolet circular dichroism (VUVCD) spectra of six proteins-myoglobin, human serum albumin, alpha-lactalbumin, thioredoxin, beta lactoglobulin, and alpha-chymotrypsinogen A-down to 170 nm in trifluoroethanol solutions (TFE: 0-50%) and down to 175 nm in methanol solutions (MeOH: 0-70%) at pH 2.0 and 25 degrees C, using a synchrotron-radiation VUVCD spectrophotometer. The contents of alpha-helices, beta-strands, turns, poly-L-proline type II helices (PPIIs), and unordered structures of these proteins were estimated using the SELCON3 program, including the numbers of alpha-helix and beta-strand segments. Furthermore, the positions of alpha-helices and beta-strands on amino acid sequences were predicted by combining these secondary-structure data with a neural-network method. All alcohol-denatured proteins showed higher alpha-helix contents (up to ~ 90%) compared with the native states, and they consisted of several long helical segments. The helix-forming ability was higher in TFE than in MeOH, whereas small amounts of beta-strands without sheets were formed in the MeOH solution. The produced alpha-helices were transformed dominantly from the beta-strands and unordered structures, and slightly from the turns. The content and mean length of alpha-helix segments decreased as the number of disulfide bonds in the proteins increased, suggesting that disulfide bonds suppress helix formation by alcohols. These results demonstrate that alcohol-denatured proteins constitute an ensemble of many long alpha-helices, a few beta-strands and PPIIs, turns, and unordered structures, depending on the types of proteins and alcohols involved. PMID- 22076922 TI - Identification of CD146 expression, angiogenesis, and lymphangiogenesis as progression, metastasis, and poor-prognosis related markers for gallbladder adenocarcinoma. AB - Gallbladder cancers (GBC) are associated with high disease-specific mortality rates because of no means of early detection and effective therapies. In this study, we investigated CD146 expression, microvessel densities, and lymph vessel densities in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using immunohistochemistry. We demonstrated that positive CD146 expression, and average microvessel and lymph vessel counts in gallbladder adenocarcinomas were significantly higher than those in peritumoral tissues, polyps, and chronic cholecystitis (ps < 0.01). Positive CD146 expression, and average microvessel and lymph vessel counts were also significantly lower in cases with well-differentiated adenocarcinoma, maximal tumor diameter <2 cm, no metastasis of lymph node, and no invasion of regional tissues than in cases with poorly differentiated adenocarcinoma, maximal tumor diameter >= 2 cm, metastasis in lymph nodes, and invasion of regional tissues (p < 0.05 or p < 0.01). Univariate Kaplan-Meier analysis showed that increased expression of CD146 (p = 0.056), higher average microvessel counts (p < 0.05), and lymph vessel counts (p < 0.05) were associated with decreased overall survival. Multivariate Cox regression analysis showed that average microvessel and lymph vessel counts (ps < 0.05) were independent prognostic predictors in gallbladder adenocarcinoma. Our study suggested that the elevated expression of CD146, angiogenesis, and lymphangiogenesis might be closely related to progression, invasion, metastasis, and prognosis of gallbladder adenocarcinoma. PMID- 22076924 TI - Acquired facial atrophy: a neglected clinical sign of POEMS syndrome. PMID- 22076923 TI - PEBP4 gene expression and its significance in invasion and metastasis of non small cell lung cancer. AB - The goal of this study was to investigate the function of phosphatidylethanolamine-binding protein 4 (PEBP4) in invasion and metastasis of non-small cell lung cancer (NSCLC). PEBP4 mRNA and protein expression in 56 cases of NSCLC tissues were detected using RT-PCR and Western blot, and the relationship between PEBP4 expression and invasion and metastasis of NSCLC was analyzed. The change in the invasive ability of human NSCLC cell line HCC827 was observed after knocking down PEBP4 expression using RNA interference. PEBP4 mRNA and protein expression in cancer tissues of patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis (p < 0.05). PEBP4 expression significantly decreased in HCC827 cells after transfection with PEBP4 siRNA (p < 0.01), and the number of HCC827 cells that migrated through Transwell chambers was significantly lower than that of non transfected control and transfected control cells (p < 0.01). PEBP4 over expression may promote the invasion and metastasis of NSCLC. PMID- 22076925 TI - Novel thermal effect at nanoshell heating by pulsed laser irradiation: hoop shaped hot zone formation. AB - Photonic nanotechnologies have good perspectives to be widely used in biophotonics. In this study we have developed an approach for calculation of nanoparticle temperature field accounting for absorbed local intensity at pulse laser radiation of composite spherical nanoparticles (nanoshells). This approach allowed us to analyze spatial inhomogeneities of light field diffracted into a nanoshell and corresponding distribution of the absorption energy and to provide numerical solution of time-dependent heat conduction equation accounting for corresponding spatially inhomogeneous distribution of heating sources. We were able to predict the appearance of a novel thermal effect - hoop-shaped hot zone on the nanoshell surface. The observed effect has potential applications in cell biology and medicine for controlled cell optoporation and nanosurgery, as well as cancer cell killing. PMID- 22076926 TI - Reproductive tissues maintain insulin sensitivity in diet-induced obesity. AB - Reproductive dysfunction is associated with obesity. We previously showed that female mice with diet-induced obesity (DIO) exhibit infertility and thus serve as a model of human polycystic ovary syndrome (PCOS). We postulated that differential insulin signaling of tissues leads to reproductive dysfunction; therefore, a comparison of insulin signaling in reproductive tissues and energy storage tissues was performed. Pituitary-specific insulin receptor knockout mice were used as controls. High-fat diet-induced stress, which leads to insulin resistance, was also investigated by assaying macrophage infiltration and phosphorylated Jun NH(2)-terminal kinase (pJNK) signaling. In lean mice, reproductive tissues exhibited reduced sensitivity to insulin compared with peripheral metabolic tissues. However, in obese mice, where metabolic tissues exhibited insulin resistance, the pituitary and ovary maintained insulin sensitivity. Pituitaries responded to insulin through insulin receptor substrate (IRS)2 but not IRS1, whereas in the ovary, both IRS1 and IRS2 were activated by insulin. Macrophage infiltration and pJNK signaling were not increased in the pituitary or ovary of lean mice relative to DIO mice. The lack of inflammation and cytokine signaling in the pituitary and ovary in DIO mice compared with lean mice may be one of the reasons that these tissues remained insulin sensitive. Retained sensitivity of the pituitary and ovary to insulin may contribute to the pathophysiology of PCOS. PMID- 22076928 TI - Myofibroblast persistence and collagen type I accumulation in the human stenotic trachea. AB - BACKGROUND: Postintubation tracheal stenosis (PITS) is associated with an increased use of assisted ventilation in intensive care units. We investigated both collagen type I accumulation and myofibroblast localization in human PITS lesions excised for surgical therapeutic procedures, compared with normal tracheas. METHODS: We analyzed 2 segments of normal tracheas and 10 segments of PITS that were stained by hematoxylin-eosin and picrosirius red techniques and processed for immunohistochemistry using antibodies against both alpha-smooth muscle actin (alpha-sma) for myofibroblast detection, and collagen type I. RESULTS: We showed a significant increase in collagen deposition in PITS specimens compared with normal tracheas. We found spindle-shaped alpha-sma positive cells (myofibroblasts) in the subepithelial layer of all pathologic tracheas, and the persistence of an intense myofibroblast network at PITS sites. CONCLUSIONS: Tracheal wall thickening in PITS is due to a deranged collagen remodeling that is related to myofibroblast activation. PMID- 22076927 TI - Inotuzumab ozogamicin murine analog-mediated B-cell depletion reduces anti-islet allo- and autoimmune responses. AB - B cells participate in the priming of the allo- and autoimmune responses, and their depletion can thus be advantageous for islet transplantation. Herein, we provide an extensive study of the effect of B-cell depletion in murine models of islet transplantation. Islet transplantation was performed in hyperglycemic B cell-deficient(MUMT) mice, in a purely alloimmune setting (BALB/c into hyperglycemic C57BL/6), in a purely autoimmune setting (NOD.SCID into hyperglycemic NOD), and in a mixed allo-/autoimmune setting (BALB/c into hyperglycemic NOD). Inotuzumab ozogamicin murine analog (anti-CD22 monoclonal antibody conjugated with calicheamicin [anti-CD22/cal]) efficiently depleted B cells in all three models of islet transplantation examined. Islet graft survival was significantly prolonged in B-cell-depleted mice compared with control groups in transplants of islets from BALB/c into C57BL/6 (mean survival time [MST]: 16.5 vs. 12.0 days; P = 0.004), from NOD.SCID into NOD (MST: 23.5 vs. 14.0 days; P = 0.03), and from BALB/c into NOD (MST: 12.0 vs. 5.5 days; P = 0.003). In the BALB/c into B-cell-deficient mice model, islet survival was prolonged as well (MST: MUMT = 32.5 vs. WT = 14 days; P = 0.002). Pathology revealed reduced CD3(+) cell islet infiltration and confirmed the absence of B cells in treated mice. Mechanistically, effector T cells were reduced in number, concomitant with a peripheral Th2 profile skewing and ex vivo recipient hyporesponsiveness toward donor-derived antigen as well as islet autoantigens. Finally, an anti-CD22/cal and CTLA4-Ig-based combination therapy displayed remarkable prolongation of graft survival in the stringent model of islet transplantation (BALB/c into NOD). Anti CD22/cal-mediated B-cell depletion promotes the reduction of the anti-islet immune response in various models of islet transplantation. PMID- 22076930 TI - Relativistic Hamiltonians for chemistry: a primer. PMID- 22076929 TI - Barx2 is expressed in satellite cells and is required for normal muscle growth and regeneration. AB - Muscle growth and regeneration are regulated through a series of spatiotemporally dependent signaling and transcriptional cascades. Although the transcriptional program controlling myogenesis has been extensively investigated, the full repertoire of transcriptional regulators involved in this process is far from defined. Various homeodomain transcription factors have been shown to play important roles in both muscle development and muscle satellite cell-dependent repair. Here, we show that the homeodomain factor Barx2 is a new marker for embryonic and adult myoblasts and is required for normal postnatal muscle growth and repair. Barx2 is coexpressed with Pax7, which is the canonical marker of satellite cells, and is upregulated in satellite cells after muscle injury. Mice lacking the Barx2 gene show reduced postnatal muscle growth, muscle atrophy, and defective muscle repair. Moreover, loss of Barx2 delays the expression of genes that control proliferation and differentiation in regenerating muscle. Consistent with the in vivo observations, satellite cell-derived myoblasts cultured from Barx2(-/-) mice show decreased proliferation and ability to differentiate relative to those from wild-type or Barx2(+/-) mice. Barx2(-/-) myoblasts show reduced expression of the differentiation-associated factor myogenin as well as cell adhesion and matrix molecules. Finally, we find that mice lacking both Barx2 and dystrophin gene expression have severe early onset myopathy. Together, these data indicate that Barx2 is an important regulator of muscle growth and repair that acts via the control of satellite cell proliferation and differentiation. PMID- 22076931 TI - Flow cytometry counting of bronchoalveolar lavage leukocytes with a new profile of monoclonal antibodies combination. AB - BACKGROUND: Differential cell count in bronchoalveolar lavage (BAL) has an important role in the diagnosis of pulmonary diseases. Optical microscopy method is usually chosen to identify BAL leukocyte populations despite its technical limitations. As there are no guidelines to make this analysis by flow cytometry (FCM), we propose a new monoclonal antibodies combination for this analysis. METHODS: Thirty-four BAL samples were stained with the monoclonal antibodies combination CD15/CD16/CD45/HLA-DR and analyzed in a 2-laser cytometer (FACSCalibur). The results were compared with those obtained by optical microscopy. RESULTS: Both methods showed a good correlation, but FCM overestimates lymphocyte population and conversely underestimates alveolar macrophage population. CONCLUSIONS: The proposed monoclonal antibodies combination is effective and reliable to identify leukocyte populations in BAL. PMID- 22076932 TI - Ten years' experience with needle biopsy in the early diagnosis of sacroiliitis. AB - OBJECTIVE: To evaluate the usefulness of needle biopsy in the diagnosis of early sacroiliitis to improve the diagnostic level and outcome of ankylosing spondylitis (AS). METHODS: One hundred nine patients in whom early AS was highly suspected, but in whom only sacroiliitis of grade I or lower on radiography/computed tomography (CT) was seen, were recruited for study. CT guided needle biopsy of the sacroiliac joints was performed, and the patients were followed up for 5-10 years. RESULTS: Of the 109 patients, magnetic resonance imaging (MRI) was used to confirm the presence or absence of sacroiliitis in 77 patients. Of these, 23 patients were determined to have sacroiliitis on MRI, and 54 had no sacroiliitis on MRI. Needle biopsy was performed on all 109 patients. Features of inflammation were found in 85 patients, which included all 23 patients with MRI evidence of sacroiliitis and 38 of the 54 patients without MRI evidence of sacroiliitis. No features of inflammation were found on needle biopsy in 24 of the patients, including the remaining 16 patients who did not have sacroiliitis on MRI. The sensitivity and specificity of MRI for the early diagnosis of sacroiliitis in these patients were 37.7% and 100%, respectively. Thirty-four patients with pathologic evidence of sacroiliitis were followed up for 5-10 years. At the study end point, 16 of these 34 patients continued to show grade I or lower changes on CT, and 18 had changes of grade II or higher. These 18 patients included 7 of the 8 patients with evidence of sacroiliitis on MRI and 6 of the 20 patients confirmed not to have MRI evidence of sacroiliitis at baseline. CONCLUSION: MRI, though of low sensitivity, is specific for the diagnosis of early sacroiliitis. Sacroiliitis can be detected earlier by needle biopsy than by MRI. PMID- 22076934 TI - Glial cells in adult neurogenesis. AB - Adult neurogenesis is an exceptional feature of the adult brain and in an intriguing way bridges between neuronal and glial neurobiology. Essentially, all classes of glial cells are directly or indirectly linked to this process. Cells with astrocytic features, for example, serve as radial glia-like stem cells in the two neurogenic regions of the adult brain, the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles, producing new neurons, create a microenvironment permissive for neurogenesis, and are themselves generated alongside the new neurons in an associated but independently regulated process. Oligodendrocytes are generated from precursor cells intermingled with those generating neurons in an independent lineage. NG2 cells have certain precursor cell properties and are found throughout the brain parenchyma. They respond to extrinsic stimuli and injury but do not generate neurons even though they can express some preneuronal markers. Microglia have positive and negative regulatory effects as constituents of the "neurogenic niche". Ependymal cells play incompletely understood roles in adult neurogenesis, but under certain conditions might exert (back-up) precursor cell functions. Glial contributions to adult neurogenesis can be direct or indirect and are mediated by mechanisms ranging from gap-junctional to paracrine and endocrine. As the two neurogenic regions differ between each other and both from the non-neurogenic rest of the brain, the question arises in how far regionalization of both the glia-like precursor cells as well as of the glial cells determines site-specific "neurogenic permissiveness." In any case, however, "neurogenesis" appears to be an essentially glial achievement. PMID- 22076933 TI - Protective effect of Calamintha officinalis Moench leaves against alcohol-induced gastric mucosa injury in rats. Macroscopic, histologic and phytochemical analysis. AB - Calamintha officinalis Moench (Lamiaceae) is an aromatic plant used since ancient times for its preservative and medicinal properties. The plant, known as 'Mentuccia' in Central Italy, is used in cooking as an aromatizant and to impart aroma and flavour to food. The methanol extract of the leaves was subjected to phytochemical and biological investigations. The extract contains polyphenols, catechic tannins and terpenes and shows radical scavenger activity. By means of HPLC analysis, eriocitrin, eriodyctiol, acacetin, linarin, benzoic acid and some phenolic acids, such as caffeic, chlorogenic, p-coumaric, were determined. The gastroprotective activity of the extract was investigated using ethanol-induced ulcer in rats, with sucralfate as a reference drug. Samples of gastric mucosa, stained by PAS and haematoxylin/eosin, were observed by light microscopy. The efficacy of the extract was comparable to that of the reference drug. Probably the gastroprotective effect depends on a synergistic action of all the compounds occurring in C. officinalis leaves, even if the antioxidant potential of the leaves plays an important role by removing damaging agents from the gastric mucosa. PMID- 22076935 TI - Resonance Raman quantification of the redox state of cytochromes b and c in-vivo and in-vitro. AB - We observe the redox state changes with respiration of cytochromes b and c in mitochondria in a living Saccharomyces cerevisiae cell as well as in isolated mitochondria with the very use of Raman microspectroscopy. The possibility of monitoring the respiration activity of mitochondria in vivo and in vitro by Raman microspectroscopic quantification of the cytochrome redox states is suggested. It will lead to a new means to assess mitochondrial respiration activity in vivo and in vitro without using any labelling or genetic manipulation. PMID- 22076936 TI - Prospective trial of chemotherapy-enhanced accelerated radiotherapy for larynx preservation in patients with intermediate-volume hypopharyngeal cancer. AB - BACKGROUND: Altered fractionation radiotherapy (RT) improves locoregional control in head and neck cancer without aggravation of late adverse events. To improve successful larynx-preservation rates in patients with resectable, intermediate volume hypopharyngeal cancer, a prospective trial of chemotherapy-enhanced accelerated RT was conducted. METHODS: Patients with T2 to T4 hypopharyngeal cancer received 40 Gray (Gy)/4 weeks to the entire neck followed by boost RT administering 30 Gy/2 weeks (1.5 Gy twice-daily fractionation). Cisplatin and 5 fluorouracil were administered concomitantly only during boost RT. RESULTS: Thirty-five patients were enrolled in this study. All patients completed this protocol as planned. After a median follow-up period for surviving patients of 59 months (24-90 months), overall survival and local control rates at 3 years were 91% (95% confidence interval, 81% to 100%), and 88% (79% to 99%), respectively. All surviving patients maintained normalcy of diets. CONCLUSION: This regimen was feasible with encouraging oncological and functional outcomes. PMID- 22076937 TI - Substituents destabilize the molecule by increasing biradicaloid character and stabilize by intramolecular charge transfer in the derivatives of benzobis(thiadiazole) and thiadiazolothienopyrazine: a computational study. AB - Keeping in view the possible applications of singlet open-shell molecules as semiconductors, non-classical derivatives of the heterocyclic rings benzobis(thiadiazole) (BBT) and its positional isomer thiadiazolothienopyrazine (TTP) are characterized using DFT methodologies. M06-2X, B3LYP and BHandHLYP functionals were used to optimize the geometries and estimate the vertical transition energies. It is observed that unlike the BHandHLYP functional (50% exchange), which gives rise to spin-contaminated solutions for all molecules in the series, M06-2X (54% exchange) affords a wavefunction either with no instability or negligible instability for most of the molecules. The results are compared with the earlier reported experimental data and those obtained herein using the spin-flip (SF)-5050 method. It is found that B3LYP does not fare well while on the other hand the M06-2X and SF-50-50 are in good agreement with the experimental results. It is seen that M06-2X TD-DFT for the molecules can be carried out without major spin contamination and also that the more time consuming CI can be avoided for the calculation of transition energies. The biradical nature of the molecules is estimated by the singlet-triplet gap. Intramolecular charge transfer is calculated. It is found that the ring substituents donate charge in the ground state, creating a zwitterionic structure. Thus the substituents play an interesting dual role, decreasing the stability of the molecule by increasing the biradical character (small HOMO-LUMO gap), and stabilization of this ground state by intramolecular charge transfer. PMID- 22076938 TI - 5-Aminoimidazole-4-carboxyamide ribonucleoside induces G(1)/S arrest and Nanog downregulation via p53 and enhances erythroid differentiation. AB - Molecular mechanisms of how energy metabolism affects embryonic stem cell (ESC) pluripotency remain unclear. AMP-activated protein kinase (AMPK), a key regulator for controlling energy metabolism, is activated in response to ATP-exhausting stress. We investigated whether cellular energy homeostasis is associated with maintenance of self-renewal and pluripotency in mouse ESCs (mESCs) by using 5 aminoimidazole-4-carboxyamide ribonucleoside (AICAR) as an activator of AMPK. We demonstrate that AICAR treatment activates the p53/p21 pathway and markedly inhibits proliferation of R1 mESCs by inducing G(1) /S-phase cell cycle arrest, without influencing apoptosis. Treatment with AICAR also significantly reduces pluripotent stem cell markers, Nanog and stage-specific embryonic antigen-1, in the presence of leukemia inhibitory factor, without affecting expression of Oct4. H9 human ESCs also responded to AICAR with induction of p53 activation and repression of Nanog expression. AICAR reduced Nanog mRNA levels in mESCs transiently, an effect not due to expression of miR-134 which can suppress Nanog expression. AICAR induced Nanog degradation, an effect inhibited by MG132, a proteasome inhibitor. Although AICAR reduced embryoid body formation from mESCs, it increased expression levels of erythroid cell lineage markers (Ter119, GATA1, Klf1, Hbb-b, and Hbb-bh1). Although erythroid differentiation was enhanced by AICAR, endothelial lineage populations were remarkably reduced in AICAR-treated cells. Our results suggest that energy metabolism regulated by AMPK activity may control the balance of self-renewal and differentiation of ESCs. PMID- 22076939 TI - Role of interferon regulatory factor 7 in serum-transfer arthritis: regulation of interferon-beta production. AB - OBJECTIVE: Innate immune responses activate synoviocytes and recruit inflammatory cells into the rheumatoid joint. Type I interferons (IFNs) play a role in autoimmunity, and IFN gene transcription is activated by IFN-regulatory factors (IRFs) in response to innate sensor recognition. The purpose of this study was to examine the effect of genetic deficiency of IRF-7 in a passive K/BxN serum transfer model of arthritis. METHODS: Passive-transfer arthritis was induced in IRF-7(-/-) mice, and additional groups were treated with IFNbeta or poly(I-C). Clinical arthritis scoring, histologic assessment, micro-computed tomography, and synovial tissue quantitative polymerase chain reaction analysis were performed. Mouse serum was analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the passive K/BxN serum-transfer model, arthritis severity was significantly increased in IRF-7(-/-) mice compared with wild-type (WT) mice. In addition, expression of IFNbeta in synovium and serum was decreased, potentially contributing to increased arthritis. IRF-7(-/-) mice injected with replacement IFNbeta had a decrease in arthritis. Poly(I-C) treatment diminished arthritis in IRF-7(-/-) mice, restored synovial IFNbeta gene expression, and increased serum levels of IFNbeta. In vitro studies demonstrated that poly(I-C) stimulation of fibroblast-like synoviocytes (FLS) from IRF-7(-/-) mice resulted in increased induction of proinflammatory gene expression as compared with FLS from WT mice; however, IFNbeta expression was not significantly different. In contrast, peritoneal macrophages from IRF-7(-/-) mice showed significantly less induction of IFNbeta in response to poly(I-C) stimulation. CONCLUSION: IRF-7 deficiency exacerbates arthritis and replacement treatment with IFNbeta or poly(I-C) decreases arthritis severity. Both macrophage- and synoviocyte-specific roles of IRF-7 likely contribute to the increased arthritis. IRF-7 might play an antiinflammatory role in passive-transfer arthritis through regulation of macrophage IFNbeta production. PMID- 22076940 TI - CD80 (B7.1) is expressed on both malignant B cells and nonmalignant stromal cells in non-Hodgkin lymphoma. AB - BACKGROUND: CD80 is a member of the B7 family of immune coregulatory proteins that mediate both immune activation and suppression. CD80 in particular has recently been shown to play an important role in supporting immune suppression through interactions with B7-H1. CD80 has been identified as a therapeutic target in non-Hodgkin lymphoma (NHL) based on limited immunohistochemical studies of CD80 expression. Clinical studies have shown that the anti-CD80 antibody galiximab is safe and clinically efficacious in follicular NHL. However, the mechanisms through which targeting CD80 inhibits tumor progression remain poorly understood. METHODS: To further define the potential of CD80 as a therapeutic target in NHL, CD80 expression was evaluated by multicolor flow cytometric analysis of primary lymphoma cell suspensions generated from 241 diagnostic biopsies of patients with NHL. RESULTS: CD80 was expressed on malignant B cells in essentially all cases of follicular lymphoma (97%; n = 115), the majority of cases of diffuse large B-cell lymphoma (90%; n = 69), marginal zone lymphoma (91%; n = 22), mantle cell lymphoma (75%; n = 12), and in about half of small lymphocytic lymphoma cases (43%; n = 23). CD80 was also present on tumor infiltrating T lymphocytes in nearly all cases. Additionally, CD80 was expressed by non-B, non-T cells in 68 and 44% of cases of follicular and diffuse large B cell NHL, respectively. CONCLUSIONS: CD80 is expressed on both malignant cells and the nonmalignant cells in NHL. Therapeutic targeting of CD80 will therefore modulate the complex intercellular interactions that define the tumor microenvironment in NHL. PMID- 22076941 TI - The beetroot component betanin modulates ROS production, DNA damage and apoptosis in human polymorphonuclear neutrophils. AB - The aim of this study was to evaluate the effect of betanin, one of the beetroot major components, on ROS production, DNA damage and apoptosis in human resting and stimulated with phorbol 12-myristate13-acetate polymorphonuclear neutrophils, one of the key elements of the inflammatory response. Incubation of neutrophils with betanin in the concentration range 2-500 uM resulted in significant inhibition of ROS production (by 15-46%, depending on the ROS detection assay). The antioxidant capacity of betanin was most prominently expressed in the chemiluminescence measurements. This compound decreased also the percentage of DNA in comet tails in stimulated neutrophils, but only at the 24 h time point. In resting neutrophils an increased level of DNA in comet tails was observed. Betanin did not affect the activity of caspase-3, in resting neutrophils, but significantly enhanced the enzyme activity in stimulated neutrophils. The western blot analysis showed, however, an increased level of caspase-3 cleavage products as a result of betanin treatment both in resting and stimulated neutrophils. The results indicate that betanin may be responsible for the effect of beetroot products on neutrophil oxidative metabolism and its consequences, DNA damage and apoptosis. The dose and time dependent effects on these processes require further studies. PMID- 22076942 TI - A tale of two polymorphic pharmaceuticals: pyrithyldione and propyphenazone and their 1937 co-crystal patent. AB - A co-crystal of two polymorphic active pharmaceutical ingredients (APIs), first reported and patented in 1937, has been prepared and thoroughly characterised, including crystal structure analysis. The existence of four crystal forms of one of the APIs, the sedative and hypnotic active pharmaceutical ingredient 3,3 diethyl-2,4(1H,3H)-pyridinedione, pyrithyldione (PYR), and of three crystal forms of the co-crystal-forming second API, the non-steroidal anti-inflammatory drug 1,2-dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenyl-3H-pyrazol-3-one, propyphenazone (PROP), has been reported previously, but they have only been partly characterised. For both compounds, none of the metastable forms exist at room temperature. DSC, hot-stage microscopy, X-ray diffraction and powder synchrotron X-ray diffraction were employed to characterise the polymorphic forms and to determine the crystal structures of forms I-III of PYR and forms I and II of PROP. PMID- 22076943 TI - Environmental, lifestyle, and familial/ethnic factors associated with myeloproliferative neoplasms. AB - Myeloproliferative neoplasms (MPNs) are characterized by overproduction of mature functional blood cells and are often associated with an acquired genetic mutation of Janus Kinase 2(V617F). The etiology of MPNs remains unknown. The aim of this article was to review and collate all known published data investigating environmental and lifestyle factors associated with MPNs. Medline, Embase, PubMed, Cochrane, and Web of Science were systematically searched using terms for MPNs and observational study designs to identify studies investigating the risk factors for MPNs published before March 2010. Of 9,156 articles identified, 19 met the selection criteria. Although the studies exhibited heterogeneity, in case definitions, study design, and risk factors investigated, several themes emerged. A strong association was found with Jewish descent, and with a family history of MPNs. Autoimmune conditions, specifically Crohn's disease, were more common in patients with MPNs. Certain occupational groups were significantly associated with MPNs including occupations with potential exposure to benzene and/or petroleum. Blood donation was associated with an increased risk of polycythemia vera specifically. The vast heterogeneity in studies identified as part of this review suggests that large scale systematic assessment of etiological factors associated with MPNs is warranted. PMID- 22076944 TI - Which dimensions of fatigue should be measured in patients with rheumatoid arthritis? A Delphi study. AB - OBJECTIVE: Rheumatoid arthritis (RA) patients experience fatigue as a multidimensional symptom. The aim of the present study was to use health professionals and patients alike to identify which dimensions of fatigue should be measured in RA. METHODS: Twelve fatigue dimensions were constructed, based on items from traditional questionnaires and items generated from interviews. Health professionals and patients evaluated these dimensions, related to an initial pool of 294 items, in a Delphi procedure. Dimensions were selected if rated important by at least 80% of the participants. RESULTS: Ten rheumatologists, 20 nurses and 15 patients participated. All fatigue dimensions were selected directly (severity, frequency, duration, changes in fatigue, perceived causes of fatigue, energy, sleep/rest, body feeling, cognition/concentration, coping, negative emotions/mood and consequences). No additional dimensions emerged from participants' comments and suggestions. CONCLUSIONS: This study revealed 12 fatigue dimensions. This underlines the multidimensionality of fatigue in RA and the need for comprehensive measurement. PMID- 22076945 TI - Acute-phase serum amyloid A regulates tumor necrosis factor alpha and matrix turnover and predicts disease progression in patients with inflammatory arthritis before and after biologic therapy. AB - OBJECTIVE: To investigate the relationship between acute-phase serum amyloid A (A SAA) and joint destruction in inflammatory arthritis. METHODS: Serum A-SAA and C reactive protein (CRP) levels, the erythrocyte sedimentation rate (ESR), and levels of matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-9, MMP-13, tissue inhibitor of metalloproteinases 1 (TIMP-1), vascular endothelial growth factor (VEGF), and type I and type II collagen-generated biomarkers C2C and C1,2C were measured at 0-3 months in patients with inflammatory arthritis commencing anti tumor necrosis factor alpha (anti-TNFalpha) therapy and were correlated with 1 year radiographic progression. The effects of A-SAA on MMP/TIMP expression on RA fibroblast-like synoviocytes (FLS), primary human chondrocytes, and RA/psoriatic arthritis synovial explant cultures were assessed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, antibody protein arrays, and gelatin zymography. RESULTS: Serum A-SAA levels were significantly (P < 0.05) correlated with MMP-3, the MMP-3:TIMP-1 ratio, C1,2C, C2C, and VEGF. The baseline A-SAA level but not the ESR or the CRP level correlated with the 28-joint swollen joint count and was independently associated with 1-year radiographic progression (P = 0.038). A-SAA increased MMP-1, MMP-3, MMP-13, and MMP/TIMP expression in RA FLS and synovial explants (P < 0.05). In chondrocytes, A-SAA induced MMP-1, MMP 3, and MMP-13 messenger RNA and protein expression (all P < 0.01), resulting in a significant shift in MMP:TIMP ratios (P < 0.05). Gelatin zymography revealed that A-SAA induced MMP-2 and MMP-9 activity. Blockade of the A-SAA receptor SR-B1 (A SAA receptor scavenger receptor-class B type 1) inhibited MMP-3, MMP-2, and MMP-9 expression in synovial explant cultures ex vivo. Importantly, we demonstrated that A-SAA has the ability to induce TNFalpha expression in RA synovial explant cultures (P < 0.05). CONCLUSION: A-SAA may be involved in joint destruction though MMP induction and collagen cleavage in vivo. The ability of A-SAA to regulate TNFalpha suggests that A-SAA signaling pathways may provide new therapeutic strategies for the treatment of inflammatory arthritis. PMID- 22076947 TI - Freezing tolerance and low molecular weight cryoprotectants in an invasive parasitic fly, the deer ked (Lipoptena cervi). AB - Insect cold hardiness is often mediated by low molecular weight cryoprotectants, such as sugars, polyols, and amino acids (AA). While many free-living northern insects must cope with extended periods of freezing ambient temperatures (Ta), the ectoparasitic deer ked Lipoptena cervi imago can encounter subfreezing Ta only during a short autumnal period between hatching and host location. Subsequently, it benefits from the body temperature of the cervid host for survival in winter. This study investigated the cold tolerance of the species by determining its lower lethal temperature (100% mortality, LLT100) during faster and slower cold acclimation, by determining the supercooling point (SCP) and by measuring the concentrations of potential low molecular weight cryoprotectants. The LLT100 of the deer ked was approximately -16 degrees C, which would enable it to survive freezing nighttime Ta not only in its current area of distribution but also further north. The SCP was -7.8 degrees C, clearly higher than the LLT100 , indicating that the deer ked displays freezing tolerance. The concentrations of free AA, especially nonessential AA, were higher in the cold acclimated deer keds similar to several other insects. The concentrations of proline increased together with gamma-aminobutyrate, arginine, asparagine, cystine, glutamate, glutamine, hydroxylysine, sarcosine, serine, and taurine. AA could be hypothesized to act as cryoprotectants by, e.g., protecting enzymes and lipid membranes from damage caused by cold. PMID- 22076946 TI - Guided migration of neural stem cells derived from human embryonic stem cells by an electric field. AB - Small direct current (DC) electric fields (EFs) guide neurite growth and migration of rodent neural stem cells (NSCs). However, this could be species dependent. Therefore, it is critical to investigate how human NSCs (hNSCs) respond to EF before any possible clinical attempt. Aiming to characterize the EF stimulated and guided migration of hNSCs, we derived hNSCs from a well established human embryonic stem cell line H9. Small applied DC EFs, as low as 16 mV/mm, induced significant directional migration toward the cathode. Reversal of the field polarity reversed migration of hNSCs. The galvanotactic/electrotactic response was both time and voltage dependent. The migration directedness and distance to the cathode increased with the increase of field strength. (Rho kinase) inhibitor Y27632 is used to enhance viability of stem cells and has previously been reported to inhibit EF-guided directional migration in induced pluripotent stem cells and neurons. However, its presence did not significantly affect the directionality of hNSC migration in an EF. Cytokine receptor [C-X-C chemokine receptor type 4 (CXCR4)] is important for chemotaxis of NSCs in the brain. The blockage of CXCR4 did not affect the electrotaxis of hNSCs. We conclude that hNSCs respond to a small EF by directional migration. Applied EFs could potentially be further exploited to guide hNSCs to injured sites in the central nervous system to improve the outcome of various diseases. PMID- 22076949 TI - Detection of circulating tumor cells in advanced head and neck cancer using the CellSearch system. AB - BACKGROUND: Early detection of circulating tumor cells (CTCs) offers the possibility of improved outcome for patients with head and neck squamous cell cancer (HNSCC). METHODS: Patients with advanced-stage HNSCC (stage III/IV) were tested for CTCs using the CellSearch system (a registered trade name), which has been approved by the U.S. Food and Drug Administration (FDA) for monitoring CTCs in other cancers. RESULTS: CTCs were detected in 6 of 15 patients with advanced stage HNSCC (range, 1-2 cells/7.5 mL of blood). CTCs were significantly associated with patients with lung nodules >1 cm (p = .04). There was also a suggestion of improved survival in the CTC-negative versus the CTC-positive patients (p = .11). CONCLUSIONS: CTCs can be successfully isolated in patients with advanced-stage HNSCC using the CellSearch system. CTC detection may be important for prognosis, evaluating treatment outcome, and for determining efficacy of adjuvant treatments. PMID- 22076948 TI - Artificial neural network in diagnosis of metastatic carcinoma in effusion cytology. AB - AIMS AND OBJECTIVES: To build an artificial neural network (ANN) model for the detection of carcinoma in effusion cytology. MATERIALS AND METHODS: We selected a total of 114 effusion cytology cases consisting of 57 each benign and malignant case. In all these cases, detailed cytological features, image morphometric data, densitometric data, and chromatin textural data were collected. Based on these data, we made a back propagation ANN model for diagnosing malignancy in effusion cytology. This network was designed as 25-2-1 (input nodes-hidden nodes-output node). Online back propagation method was applied for training the network. The training of the network was continued until the network error was reduced to 0.000654. Simultaneously, we also performed logistic regression (LR) analysis test to compare with ANN model performance. RESULT: ANN model worked excellent after adequate training. With the help of this model, it was possible to identify correctly all the malignant cases in validation and test set. The result of the multivariate LR analysis was also similar as that of ANN model and all the cases were also classified correctly. CONCLUSIONS: In this study, we successfully constructed an ANN model to diagnose metastatic carcinoma in effusion cytology. ANN is very promising in the diagnosis of metastatic carcinoma in effusion cytology. In future, ANN model may help the cytopathologist to diagnose the difficult cases in effusion fluid. PMID- 22076950 TI - Gingko biloba extract inhibits oxidative stress and ameliorates impaired glial fibrillary acidic protein expression, but can not improve spatial learning in offspring from hyperhomocysteinemic rat dams. AB - We aimed to study the effects of gingko biloba extract (EGb) on oxidative stress, astrocyte maturation and cognitive disfunction in offspring of hyperhomocysteinemic rats. Hyperhomocysteinemia was induced in the pregnant rats by administration of methionine (1 gr/kg body weight) dissolved in drinking water throughout pregnancy. One group of animals has received same amount of methionine plus 100 mg/kg/day EGb during pregnancy. On the postnatal day 1, half of the pups from all groups were sacrificed to study the lipid peroxidation (LPO) in different subfractions of brain. Other half of pups were tested in Morris water maze to assess differences in learning and memory performance at the 75 days of age. Maternal hyperhomocysteinemia significantly increased LPO levels especially in mitochondrial subfraction of fetal pup brains. EGb significantly prevented this LPO inrease. Methionine administration to animals reduced glial fibrillary acidic protein (GFAP) expression in pup brains significantly. EGb administration improved GFAP expression significantly. Offspring of hyperhomocysteinemic animals had poor long term spatial memory performance on Morris water maze and EGb administration had no effect on impaired spatial memory. In conclusion, maternally induced hyperhomocysteinemia significantly increased oxidative stress, decreased expression of GFAP and impaired learning performance. PMID- 22076951 TI - Ultrathin platinum nanowire catalysts for direct C-N coupling of carbonyls with aromatic nitro compounds under 1 bar of hydrogen. AB - Traditionally important in the pharmaceutical, agrochemical, and synthetic dye industries, C-N coupling has proved useful for the preparation of a number of valuable organic compounds. Here, a new method for the direct one-pot reductive C N coupling from carbonyl and aromatic nitro compounds is described. Employing ultrathin platinum nanowires as the catalyst and hydrogen as the reducing agent, N-alkylamines were achieved in high yields. Debenzylation products were not detected after prolonged reaction times. Time-dependent analysis, ReactIR spectroscopy and DFT calculations revealed that the C-N coupling proceeded through a different mechanism than traditional "reductive amination." N Alkylamines were directly obtained by intermolecular dehydration over platinum nanowires under a hydrogen atmosphere, instead of intramolecular water elimination and imine hydrogenation. PMID- 22076952 TI - The potential role of pre-transplant HBcIgG seroposivity as predictor of clinically relevant cytomegalovirus infection in patients with lymphoma undergoing autologous hematopoietic stem cell transplantation: a study from the Rome Transplant Network. AB - Despite the increased use of intensive immunosuppressive chemo-immunotherapies in patients with lymphoma observed in the last decade, current data on cytomegalovirus (CMV) infection following autologous stem cell transplantation (Auto-SCT) are very limited. To address this peculiar aspect, a retrospective study on a cohort of 128 adult patients consecutively transplanted for lymphoma in three Hematology Institutions was performed with the aim to determine the incidence of and the risk factors for CMV symptomatic infection and/or end-organ disease. Sixteen patients (12.5%) required specific antiviral therapy and 4/16 died (25%); transplant-related mortality (TRM) was significantly influenced by CMV infection (P = 0.005). In univariate analysis, a pre-transplant HBcIgG seropositivity, HBV infection according to clinical-virological definitions, a pre-transplant Rituximab treatment, a diagnosis of B-cell non-Hodgkin lymphoma, and age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection. In multivariate analysis, only a pre transplant HBcIgG seropositivity (P = 0.008) proved to be an independent predictor of a clinically relevant CMV infection. These results suggest that a pre-transplant HBcIgG seropositivity could be considered as an independent predictor factor of clinically relevant CMV infection after Auto-SCT. PMID- 22076953 TI - The association of illness perceptions with physical and mental health in systemic sclerosis patients: an exploratory study. AB - OBJECTIVE: The aim of the present study was to evaluate the association between illness perceptions and the ability to cope with physical and mental health problems in a large cohort of systemic sclerosis (SSc) patients. METHODS: This was a cross-sectional study in 217 systemic sclerosis patients from the Belgian Systemic Sclerosis Cohort. Illness perception and coping were measured by the Revised Illness Perception Questionnaire and a coping questionnaire--the Coping Orientation of Problem Experience inventory (COPE). Physical and mental health related quality of life was measured by the 36-item short-form health survey (SF 36), as were disease activity and several severity parameters. The relationship between illness perceptions and the ability to cope with physical/mental health problems was examined using multiple linear regression analysis. RESULTS: According to LeRoy's classification, 49 patients had limited SSc (lSSc), 129 had limited cutaneous SSc (lcSSc) and 39 had diffuse cutaneous SSc (dcSSc). Median disease duration was five years and the modified Rodnan skin score was 4. Good physical health was significantly associated with the lcSSc subtype and low disease activity (p < 0.01 and p < 0.05, respectively). The perception of 'serious consequences' and strong 'illness identity' correlated with poor physical health (p < 0.001). Good mental health was associated with low illness identity scores and low 'emotional response' scores (p < 0.001). Coping variables were less significantly correlated with physical and mental health compared with the illness perception items. CONCLUSION: Illness representations contribute more than classical disease characteristics to physical and mental health. PMID- 22076954 TI - New pemetrexed-peptide conjugates: synthesis, characterization and in vitro cytostatic effect on non-small cell lung carcinoma (NCI-H358) and human leukemia (HL-60) cells. AB - Pemetrexed (Pem) is a novel antimetabolite type of anticancer drug that demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung carcinoma and malignant pleural mesothelioma. It inhibits enzymes involved in the folate pathway, for which the presence of its free carboxylic groups is necessary. The heteroaromatic ring system of Pem has a modifiable amino group, which opens a possibility to apply a new strategy to conjugate Pem to carrier molecules. Considering this as well as the necessity of untouched carboxylic groups of Pem in the new conjugates, we developed a new synthesis strategy. Here, we describe the synthesis and the characterization of new Pem-peptide conjugates in which cell-penetrating octaarginine or/and lung targeting H-Ile-Glu-Leu-Leu-Gln-Ala-Arg-NH(2) peptide is attached to the drug by thioether bond. The conjugates characterized by RP-HPLC and MS exhibited cytostatic effect in vitro on non-small cell lung carcinoma as well as on human leukemia cell lines. The IC(50) values of the conjugates were similar, but the conjugates with H-Ile-Glu-Leu-Leu-Gln-Ala-Arg-NH(2) sequence were slightly more effective. Our data show that the in vitro cytostatic effect of the free Pem was essentially maintained after conjugation with cell-penetrating or cell-targeting peptides. Thus, the conjugation strategy reported could lead to the development of a new generation of active Pem conjugates. PMID- 22076955 TI - Pathways for plasmalemmal repair mediated by PKA, Epac, and cytosolic oxidation in rat B104 cells in vitro and rat sciatic axons ex vivo. AB - Plasmalemmal repair (sealing) is necessary for survival of damaged eukaryotic cells. Ca(2+) influx through plasmalemmal disruptions activates pathways that initiate sealing, which is commonly assessed by exclusion of extracellular dye. These sealing pathways include PKA, Epac, and cytosolic oxidation. In this article, we investigate whether PKA, Epac, and/or cytosolic oxidation, activate specific proteins required to produce a plasmalemmal seal. We report that toxin cleavage of proteins required for neurotransmitter release (SNAP-25), inhibition of Golgi trafficking (with Brefeldin A: Bref A) or inhibition of N-ethylmaleimide sensitive factor (NSF) all decrease sealing of rat B104 hippocampal cells with transected neuritis in vitro. Epac, but not PKA or cytosolic oxidation, partly overcomes the decrease in sealing produced by cleavage of SNAP-25. PKA and increased cytosolic oxidation, but not Epac, can partly overcome the decrease in sealing due to Bref A. PKA, Epac, and/or cytosolic oxidation cannot overcome NSF inhibition. Substances that affect plasmalemmal sealing of B104 neurites in vitro have similar effects on plasmalemmal sealing in rat sciatic axons ex vivo. From these and other data, we propose a model of plasmalemmal sealing having three redundant, evolutionarily conserved, parallel pathways that all converge on NSF. PMID- 22076956 TI - A grumpy old man. PMID- 22076957 TI - Exploring the effect of metal ions and counteranions on the structure and magnetic properties of five dodecanuclear Co(II) and Ni(II) clusters. AB - We present the synthesis, characterization of the structures, and magnetic properties of five isostructural dodecanuclear coordination clusters of Ni(II) and Co(II): [Co(12)(bm)(12)(NO(3))(O(2)CMe)(6)(EtOH)(6)](NO(3))(5) (1), [Ni(12)(bm)(12)(NO(3))(O(2)CMe)(6)(H(2)O)(3)(EtOH)(3)](NO(3))(5).2H(2)O (2), mixed-metal composition (Ni/Co 1:1) [Co(6)Ni(6)(bm)(12)(NO(3))(O(2)CMe)(6)(NO(3))(5) (3), and [M(12)(bm)(12)(NO(3))(O(2)CMe)(6)(EtOH)(6)](ClO(4))(5) (M=Co (4), Ni (5)), in which Hbm=(1H-benzimidazol-2-yl)methanol. They consist of analogous structural cores that are constructed by three cubanes (M(4)O(4)) that surround the templating nitrate and bridging auxiliary acetate and the directing ligands bm. They have different magnetic behaviors. Whereas there is the absence of the out of-phase ac susceptibility (chi'') for the Ni(II)-based compounds 2 and 5, the Co(II)-containing compounds 1, 3, and 4 have prominent chi'' signals that exhibit frequency dependence, which indicates slow magnetic relaxation behavior above 1.8 K. In particular, the larger perchlorate counterions in 4 further change the overall correlation interaction between clusters, thus leading to an enhanced blocking temperature for the less-symmetrical 4 (pseudo-C(3)) relative to 1 and 3 (true C(3)). Interestingly, electrospray ionization mass spectrometry (ESI-MS) indicates that the three dodecanuclear clusters of 1-3 retain their compositions in solution. The mixed-metal cluster cores of 3 are formed based on the nature of the interchangeability between metal centers in solution. PMID- 22076958 TI - CD133 and CD44 are universally overexpressed in GIST and do not represent cancer stem cell markers. AB - Although imatinib mesylate has been a major breakthrough in the treatment of advanced gastrointestinal stromal tumors (GIST), complete responses are rare and most patients eventually develop resistance to the drug. Thus, the possibility of an imatinib-insensitive cell subpopulation within GIST tumors, harboring stem cell characteristics, may be responsible for the clinical failures. However, the existence of a cancer stem cell component in GIST has not been yet established. This study was aimed to determine whether expression of commonly used stem cell markers in other malignancies, that is, CD133 and CD44, might identify cells with characteristics of cancer stem/progenitor cells in human GIST. CD133 and CD44 expression in GIST explants was analyzed by flow cytometry, immunofluorescence, and gene expression. Their transcription levels were correlated with clinical and molecular factors in a large, well-annotated cohort of GIST patients. FACS sorted GIST cells based on CD133 and CD44 expression were isolated and used to assess phenotypic characteristics, ability to maintain their surface expression, sensitivity to imatinib, and expression signature. The enrichment in CD133/CD44 cells in the side population (SP) assay was also investigated. CD133 expression was consistently found in GIST. CD133(-) cells formed more colonies, were more invasive in a matrigel assay, and showed enrichment in the SP cells, compared to CD133(+) cells. CD133 expression was also detected in the two imatinib-sensitive GIST cell lines, while was absent in the imatinib-resistant lines. Our results show that CD133 and CD44 are universally expressed in GIST, and may represent a lineage rather than a cancer stem cell marker. PMID- 22076960 TI - Frameless stereotactic targeting devices: technical features, targeting errors and clinical results. AB - BACKGROUND: Brain biopsies (BB) and depth electrode placements (DEP) are increasingly performed using frameless stereotactic targeting devices. This paper is intended to provide a comprehensive review of the technical features, targeting errors and clinical results. METHODS: A PubMed literature search from 1995-2010 was performed. RESULTS: (A) Modified stereotactic arcs, (B) arm-based devices with and without aiming facilities, and (C) skull affixed devices were found. Guidance technologies were navigation systems (all groups), prospective stereotaxy and custom designed platforms (group C). Mean total errors ranged between 4.4 and 5.4 mm for BB and 2.0 and 3.2 mm for DEP. Diagnostic yield of BB was 89-100%. The clinical success rate for DEP was 96-100%. CONCLUSIONS: Frameless stereotactic targeting devices may reach targeting errors and clinical results comparable with standard frame-based stereotaxy. Advantages and disadvantages of different devices should be acknowledged to ensure optimal technical performance. PMID- 22076959 TI - Sexual dimorphism and bilateral asymmetry of syrinx and vocal tract in the European starling (Sturnus vulgaris). AB - Sexually dimorphic vocal behavior in zebra finches (Taeniopygia guttata) is associated with a 100% larger syrinx in males and other morphological adaptations of the sound source. The songbird syrinx consists of two independent sound sources, whose specialization for different spectral ranges may be reflected in morphological properties, but the morphology of labia and syringeal skeleton have not been investigated for lateralized specializations. Similarly, little is known whether the morphology of the songbird vocal tract reflects differences in vocal behavior. Here, we tested the hypothesis that different vocal behavior and specialization is reflected in the morphology. We investigated syringeal and upper vocal tract morphology of male and female European starlings (Sturnus vulgaris). Female starlings exhibit smaller vocal repertoires and sing at lower rates than males. In males, the left syrinx produces mostly low frequencies, while the right one is used for higher notes. Macroscopic and histological techniques were used to record nineteen measurements from the syrinx and the vocal tract which were tested for sexual differences in syrinx and vocal tract and for lateral asymmetry within the syrinx. Sexually dimorphic vocal behavior is reflected in the morphology of the starling syrinx. Males have a larger syrinx with the size difference attributable to increased muscle mass and three enlarged elements of the syringeal skeleton. The upper vocal tract, however, does not differ between males and females. Distinct lateralization was found in two elements of the syringeal skeleton of females, and the labia in the left syrinx are larger than those on the right in both sexes. The sexual dimorphism of the syringeal size is smaller in starlings (35%) than in zebra finches (100%), which is consistent with the different vocal behavior of females in both species. The morphological differences between the two sound sources are discussed in relation to their vocal performance. PMID- 22076961 TI - Synthesis and NMR elucidation of novel tetrapeptides. AB - The synthesis and NMR elucidation of Ala-Val-Pro-Ile and five novel peptide-based derivatives are reported. These peptides mimic the natural second mitochondria derived activator of caspase (Smac) protein. Purification was achieved using preparative HPLC and the NMR elucidation of all compounds is reported for the first time. A series of overlapping signals were observed in the 1D NMR spectra thus making assignment a difficult task to undertake. The use of 2D NMR techniques with the inclusion of efficient adiabatic symmetrized ROESY proved to be an effective tool in overcoming these difficulties. PMID- 22076962 TI - Vancomycin-resistant Enterococcus bacteremia: an evaluation of treatment with linezolid or daptomycin. AB - BACKGROUND: Due to high rates of resistance and a limited number of efficacious antimicrobials for vancomycin-resistant Enterococcus (VRE), appropriate antibiotic selection is vital to treatment success. The purpose of this study was to assess clinical and microbiologic outcomes associated with the use of linezolid or daptomycin in the treatment of VRE bacteremia. METHODS: A retrospective analysis of adult patients with VRE bacteremia between January 2004 and July 2009 was conducted at a tertiary care hospital in the United States. Clinical and microbiologic outcomes for both therapies were evaluated using multiple criteria. RESULTS: Of the 361 patients with VRE bacteremia identified, 201 were included in the study (linezolid group, n = 138; daptomycin group, n = 63). More patients in the daptomycin group had hematologic malignancies (33% vs 14%) or received liver transplants (13% vs 4%). There was no difference in clinical or microbiologic cure between the linezolid and daptomycin groups (74% vs 75% and 94% vs 94%, respectively). Recurrence was documented in 3% of linezolid patients vs 12% of daptomycin patients (P = 0.0321). Reinfection was noted in 1% of patients in the linezolid group vs 6% of patients in the daptomycin group (P not significant). The average length of stay (LOS) was 37 days for the linezolid group vs 40 days for the daptomycin group (P not significant). Overall mortality was 20%, occurring in 25/138 linezolid patients vs 15/63 daptomycin patients (P not significant). CONCLUSIONS: No differences in clinical or microbiologic cure rates, LOS, or mortality were identified between the groups. Various factors may have contributed to the significantly higher recurrence of VRE bacteremia in daptomycin patients. This study suggests that linezolid and daptomycin appear equally efficacious in the treatment of VRE bacteremia. PMID- 22076964 TI - Hippocampal activity during recognition memory co-varies with the accuracy and confidence of source memory judgments. AB - It has been proposed that the hippocampus selectively supports retrieval of contextual associations, but an alternative view holds that the hippocampus supports strong memories regardless of whether they contain contextual information. We employed a memory test that combined the 'Remember/Know' and source memory procedures, which allowed test items to be segregated both by memory strength (recognition accuracy) and, separately, by the quality of the contextual information that could be retrieved (indexed by the accuracy/confidence of a source memory judgment). As measured by fMRI, retrieval related hippocampal activity tracked the quality of retrieved contextual information and not memory strength. These findings are consistent with the proposal that the hippocampus supports contextual recollection rather than recognition memory more generally. PMID- 22076965 TI - The multiple roles of the cyclin-dependent kinase inhibitory protein p57(KIP2) in cerebral cortical neurogenesis. AB - The members of the CIP/KIP family of cyclin-dependent kinase (CDK) inhibitory proteins (CKIs), including p57(KIP2), p27(KIP1), and p21(CIP1), block the progression of the cell cycle by binding and inhibiting cyclin/CDK complexes of the G1 phase. In addition to this well-characterized function, p57(KIP2) and p27(KIP1) have been shown to participate in an increasing number of other important cellular processes including cell fate and differentiation, cell motility and migration, and cell death/survival, both in peripheral and central nervous systems. Increasing evidence over the past few years has characterized the functions of the newest CIP/KIP member p57(KIP2) in orchestrating cell proliferation, differentiation, and migration during neurogenesis. Here, we focus our discussion on the multiple roles played by p57(KIP2) during cortical development, making comparisons to p27(KIP1) as well as the INK4 family of CKIs. PMID- 22076966 TI - Microwave-induced formation of platinum nanostructured networks with superior electrochemical activity and stability. AB - Platinum nanostructured networks (PNNs) can be synthesized through the chemical reduction of H(2)PtCl(6) by benzyl alcohol under microwave irradiation without the introduction of any surfactants, templates, or seeds. The synthesis route utilizes benzyl alcohol as both the reductant and the structure-directing agent, and thus, the process is particularly simple and highly repeatable. The formation of the PNN structure was ascribed to the collision-induced fusion of Pt nanocrystals owing to the cooperative functions of microwave irradiation and benzyl alcohol. Compared with a commercial Pt/C catalyst, the as-prepared PNNs possessed superior electrochemical activity and stability on the oxidation of methanol because of the unique 3D nanostructured networks and abundant defects formed during the assembly process. This study may provide a facile microwave induced approach for the synthesis of other 3D nanostructured noble metals or their alloys. PMID- 22076967 TI - Microwave-assisted synthesis, hypolipidemic and hypoglycemic activity of some novel 2-(4-(2-Amino-6-(4-substituted phenyl)-pyrimidin-4-yl)-phenoxy)-2-methyl propanoic acid derivatives. AB - A novel series of aminopyrimidines containing the phenoxy isobutyric acid group as a pharmacophore was synthesized using conventional and microwave assisted methods of synthesis. The compounds were synthesized in good yields (70-89%) by the microwave-assisted one-pot protocol in much shorter reaction times. The synthesized compounds were evaluated for their hypolipidemic and hypoglycemic activity by high-fat diet-induced hyperlipidemia and hyperglycemia in male Sprague-Dawley rats. The present investigation showed significant antihyperlipidemic and antihyperglycemic activity for all compounds of the series when compared with the standard drug. Structure-activity relationship (SAR) for the series were developed by comparing total lipid profile data of synthesized compounds with fenofibrate as standard drug. PMID- 22076969 TI - Anxiety disorders and risk for suicide: why such controversy? PMID- 22076970 TI - Cognitive-behavioral group therapy versus group psychotherapy for social anxiety disorder among college students: a randomized controlled trial. AB - OBJECTIVE: In this randomized controlled trial, cognitive-behavioral group therapy (CBGT) for social anxiety disorder (SAD) was compared to group psychotherapy (GPT), a credible, structurally equivalent control condition that included only nonspecific factors of group treatment (such as group dynamics). METHODS: Participants were 45 college students at the University of Colorado with a primary diagnosis of SAD. Each treatment condition comprised eight group sessions lasting 2 hr each. Independent assessors (blind to treatment assignment) assessed participants at baseline and posttreatment with the Clinical Global Impression Scale (CGI) and the Liebowitz Social Anxiety Scale (LSAS). RESULTS: Both treatments were found to be equally credible. There were five noncompleters in the CBGT condition (21.7%) and only one in the GPT condition (4.3%). There were no statistically significant differences posttreatment (controlling for pretreatment scores) between the two treatment conditions, and both treatments were found to be efficacious. Effect sizes for CBGT were similar to earlier studies, and adherence ratings revealed excellent adherence. CONCLUSIONS: Treatment of SAD appears to be moving toward individual CBT, partly because of high attrition rates and underutilization of group dynamics in group CBT. However, group therapy has unique therapeutic ingredients, and it may be too early to give up on group treatment altogether. Discussion of these findings included future directions with this treatment modality, especially whether these two types of group treatment could be combined and whether such combination might serve to decrease attrition, enhance efficacy, and facilitate dissemination. PMID- 22076971 TI - Fear conditioning is disrupted by damage to the postsubiculum. AB - The hippocampus plays a central role in spatial and contextual learning and memory, however relatively little is known about the specific contributions of parahippocampal structures that interface with the hippocampus. The postsubiculum (PoSub) is reciprocally connected with a number of hippocampal, parahippocampal and subcortical structures that are involved in spatial learning and memory. In addition, behavioral data suggest that PoSub is needed for optimal performance during tests of spatial memory. Together, these data suggest that PoSub plays a prominent role in spatial navigation. Currently it is unknown whether the PoSub is needed for other forms of learning and memory that also require the formation of associations among multiple environmental stimuli. To address this gap in the literature we investigated the role of PoSub in Pavlovian fear conditioning. In Experiment 1 male rats received either lesions of PoSub or Sham surgery prior to training in a classical fear conditioning procedure. On the training day a tone was paired with foot shock three times. Conditioned fear to the training context was evaluated 24 hr later by placing rats back into theconditioning chamber without presenting any tones or shocks. Auditory fear was assessed on the third day by presenting the auditory stimulus in a novel environment (no shock). PoSub lesioned rats exhibited impaired acquisition of the conditioned fear response as well as impaired expression of contextual and auditory fear conditioning. In Experiment 2, PoSub lesions were made 1 day after training to specifically assess the role of PoSub in fear memory. No deficits in the expression of contextual fear were observed, but freezing to the tone was significantly reduced in PoSub lesioned rats compared to shams. Together, these results indicate that PoSub is necessary for normal acquisition of conditioned fear, and that PoSub contributes to the expression of auditory but not contextual fear memory. PMID- 22076973 TI - DNA-binding small-ligand-immobilized surface plasmon resonance biosensor for detecting thymine-related single-nucleotide polymorphisms. AB - A surface plasmon resonance (SPR) biosensor that carries DNA-binding small ligands has been developed for the detection of single-nucleotide polymorphisms (SNPs). 3,5-Diaminopyrazine derivatives, with a hydrogen-bonding profile fully complementary to the thymine base, were utilized as recognition elements on the sensor surface, and a target single-stranded DNA sequence was hybridized with a DNA probe containing an abasic site to place this site opposite a nucleobase to be detected. In a continuous flow of sample solutions buffered to pH 6.4 (0.25 M NaCl), the 3,5-diaminopyrazine-based SPR sensor can detect an orphan nucleobase in the duplex with a clear selectivity for thymine over cytosine, guanine, and adenine (5'-GTT GGA GCT GXG GGC GTA GGC-3'/3'-CAA CCT CGA CNC CCG CAT CCG-5'; X=abasic site, N=target nucleobase G, C, A, or T). The SPR response was linear in the concentration range 10-100 nM. Allele discrimination is possible based on the combination of different binding surfaces in a flow cell of the SPR system, which is demonstrated for the analysis of the thymine/cytosine mutation present in 63 meric polymerase chain reaction (PCR) amplification products (Ha-ras gene, codon 12, antisense strand). Comparison with a bulk assay based on 3,5 diaminopyrazine/DNA binding shows that the immobilization of 3,5-diaminopyrazine derivatives on the SPR sensor allows more sensitive detection of the target DNA sequence, and binding selectivity can be tuned by controlling the salt concentration of sample solutions. These features of the DNA-binding small molecule-immobilized SPR sensor are discussed as a basis for the design of SPR biosensors for SNP genotyping. PMID- 22076974 TI - Glutamate carboxypeptidase II and folate deficiencies result in reciprocal protection against cognitive and social deficits in mice: implications for neurodevelopmental disorders. AB - Interactions between genetic and environmental risk factors underlie a number of neuropsychiatric disorders, including schizophrenia (SZ) and autism (AD). Due to the complexity and multitude of the genetic and environmental factors attributed to these disorders, recent research strategies focus on elucidating the common molecular pathways through which these multiple risk factors may function. In this study, we examine the combined effects of a haplo-insufficiency of glutamate carboxypeptidase II (GCPII) and dietary folic acid deficiency. In addition to serving as a neuropeptidase, GCPII catalyzes the absorption of folate. GCPII and folate depletion interact within the one-carbon metabolic pathway and/or of modulate the glutamatergic system. Four groups of mice were tested: wild-type, GCPII hypomorphs, and wild-types and GCPII hypomorphs both fed a folate deficient diet. Due to sex differences in the prevalence of SZ and AD, both male and female mice were assessed on a number of behavioral tasks including locomotor activity, rotorod, social interaction, prepulse inhibition, and spatial memory. Wild-type mice of both sexes fed a folic acid deficient diet showed motor coordination impairments and cognitive deficits, while social interactions were decreased only in males. GCPII mutant mice of both sexes also exhibited reduced social propensities. In contrast, all folate-depleted GCPII hypomorphs performed similarly to untreated wild-type mice, suggesting that reduced GCPII expression and folate deficiency are mutually protective. Analyses of folate and neurometabolite levels associated with glutamatergic function suggest several potential mechanisms through which GCPII and folate may be interacting to create this protective effect. PMID- 22076975 TI - Does one keto group matter? Structure-activity relationships of glycyrrhetinic acid derivatives modified at position C-11. AB - Several triterpenoic acids display a remarkable cytotoxicity on tumor cells. Glycyrrhetinic acid - the main content of the licorice root - possesses an apoptotic effect on tumor cells. Previous studies pointed out the presence of a keto group at position C-11 in glycyrrhetinic acid derivatives as the main reason for its apoptotic activity. Several pairs of derivatives were synthesized differing only at position C-11. These compounds were tested in a sulforhodamine B colorimetric assay for cytotoxicity screening on 12 tumor cell lines and mouse embryonic fibroblasts (NIH3T3). Our results show that there is no direct relation between the existence of the C-11 keto group and the apoptotic activity of the compounds. PMID- 22076976 TI - Results of a prospective study of positron emission tomography-directed management of residual nodal abnormalities in node-positive head and neck cancer after definitive radiotherapy with or without systemic therapy. AB - BACKGROUND: The purpose of this study was to present our prospectively evaluated positron emission tomography (PET)-directed policy for managing the neck in node positive head and neck squamous cell carcinoma (N+HNSCC) after definitive radiotherapy (RT) with or without concurrent systemic therapy. METHODS: One hundred twelve consecutive patients who achieved a complete response at the primary site underwent a 12-week posttherapy nodal response assessment with PET and diagnostic CT. Patients with an equivocal PET underwent a repeat PET 4 to 6 weeks later. Patients with residual CT nodal abnormalities deemed PET-negative were uniformly observed regardless of residual nodal size. RESULTS: Median follow up from commencement of RT was 28 months (range, 13-64 months). Residual CT nodal abnormalities were present in 50 patients (45%): 41 PET-negative and 9 PET positive. All PET-negative residual CT nodal abnormalities were observed without subsequent isolated nodal failure. CONCLUSION: PET-directed management of the neck after definitive RT in node-positive HNSCC appropriately spares neck dissections in patients with PET-negative residual CT nodal abnormalities. PMID- 22076977 TI - Preoperative ultrasonographic tumor characteristics as a predictive factor of tumor stage in papillary thyroid carcinoma. AB - BACKGROUND: The purpose of this study was to evaluate the usefulness of tumor characteristics on ultrasonography for predicting the pathologic stage of papillary thyroid carcinoma. METHODS: We evaluated 354 patients who underwent surgery for papillary thyroid carcinoma (<=2 cm). We analyzed the preoperative ultrasonography findings such as tumor size, shape, margin, echogenicity, calcification, vascularity, and contact with the capsule. RESULTS: Tumor size, echogenicity, and contact with the capsule were predictive for the presence of extrathyroid extension. Size and echogenicity were significantly associated with central lymph node metastasis in the multivariate analysis. Some ultrasonography characteristics such as round shape, well-defined margin, and isoechoic echogenicity were negative predictive factors for extrathyroid extension and central lymph node metastasis. CONCLUSION: Preoperative tumor characteristics on ultrasonography correlated with several prognostic factors for papillary thyroid carcinoma and may serve as preoperative supplementary markers for determining the optimal extent of surgery. PMID- 22076978 TI - (99m)TC-octreotide scintigraphy and somatostatin receptor subtype expression in juvenile nasopharyngeal angiofibromas. AB - BACKGROUND: The main goal of the study was the analysis of somatostatin receptor (SSTR) expression on juvenile nasopharyngeal angiofibroma (JNA) cells and a subsequent analysis of the utility of SST analog-based scintigraphy in JNA diagnostics. METHODS: Nine JNA cases were analyzed. All tissue samples were analyzed for the expression of SSTRs. In 2 cases, scintigraphy was performed after the intravenous (IV) administration of an SST analog. MRI of the craniofacial region was subsequently performed. RESULTS: The SST analogues were accumulated in areas matching pathologic tissue in the nasopharynx. Immunohistochemical evaluation of the tissue samples proved the overexpression of SSTRs. CONCLUSIONS: SSTRs are overexpressed on JNA cells. The SST analog (99m)TC octreotide is effectively bound to JNA cells. SST analogues might be used in the diagnostics and treatment of primary, recurrent, or residual JNA. PMID- 22076979 TI - Adjuvant therapy with flutamide for presurgical volume reduction in juvenile nasopharyngeal angiofibroma. AB - BACKGROUND: Although 2 studies totaling 11 cases have indicated some benefit of anti-androgen treatment with flutamide on juvenile nasopharyngeal angiofibroma (JNA), it is not part of contemporary practice. METHODS: Our approach was through a prospective, single-arm, before-and-after study, in which 20 patients with advanced JNA (Radkowski stage IIB-IIIB) were administered flutamide (per oral: 10 mg kg(-1) day(-1) * 6 weeks) prior to surgical excision. Pretherapy and posttherapy tumor volume measurements were established by MRI. Periodic assessments were recorded of liver, kidney functions, testosterone levels, and secondary sexual characteristics. RESULTS: Prepubertal and postpubertal cases responded differently (p < .05). Prepubertal cases had inconsistent and minimal responses; 13/15 postpubertal cases demonstrated measurable volume reduction (mean, 16.5%; maximum, 40%). Two cases with optic nerve compression had visual improvement. Volume reduction correlated with serum testosterone level (r = .53; p < .05). No significant toxicity was noted, with the exception of transient breast tenderness. CONCLUSIONS: Prepubertal and postpubertal patients differ in their response to flutamide. In postpubertal patients, 6 weeks preoperative use is safe and leads to partial tumor regression. Tumor regression from adjacent vital structures may facilitate surgical excision and limit morbidity. PMID- 22076980 TI - Role of parathyroid hormone monitoring during parathyroidectomy. AB - BACKGROUND: The value of intraoperative parathyroid hormone (IOPTH) monitoring in parathyroidectomy has been previously debated. METHODS: This retrospective analysis was of 240 patients, operated on for primary hyperparathyroidism (PHPT) between January 2002 and January 2006 and categorized into 3 groups by preoperative and intraoperative modalities: group 1 (n = 109), technetium 99m sestamibi (MIBI), ultrasonography, and IOPTH; group 2 (n = 102), ultrasonography and MIBI; and group 3 (n = 29), ultrasonography and IOPTH. Sensitivity and specificity were calculated. RESULTS: In group 1, IOPTH increased the success rate from 97% to 99%. In group 2, ultrasonography and MIBI were concordant in 95% of cases. In group 3, IOPTH increased the sensitivity from 89% to 96%. The duration of surgery was longer (p < .0001) when IOPTH was applied. CONCLUSIONS: When ultrasonography and MIBI are used, the additional benefit of IOPTH is marginal, especially given the longer duration of surgery. Ultrasonography and additional IOPTH yield good success rates when MIBI is not available. PMID- 22076981 TI - Lymph node metastasis in nasal vestibule cancer: a review. AB - BACKGROUND: Squamous cell carcinoma of the nasal vestibule (SCCNV) is an uncommon malignancy. Our purpose is to define the incidence of simultaneous and delayed regional metastasis in SCCNV according to the available literature. METHODS: Articles discussing SCCNV and addressing the issue of regional lymph node metastases were reviewed. CONCLUSION: SCCNV is an uncommon form of cancer, possibly originating in the mucocutaneous junction. The incidence of lymph node metastasis is variably reported. The data in the literature do not provide a solid basis for recommendations on elective treatment of the neck. Thorough examination of the neck is recommended, preferably with modern imaging techniques. PMID- 22076982 TI - Cutaneous squamous cell carcinoma of the head and neck metastasizing to the parotid gland--a review of current recommendations. AB - Cutaneous squamous cell carcinoma (SCC) of the head and neck may metastasize in up to 5% of patients, with the parotid lymph nodes the most frequent site for spread. Metastases frequently show delayed presentation after the primary cancer had been treated. The optimum treatment should be surgery followed by adjuvant radiotherapy, with an appropriate parotidectomy, and preservation of the facial nerve if not involved by tumor and treatment to the neck. In a clinically N0 neck, levels I to III should be cleared for facial primaries, levels II to III for anterior scalp and external ear primaries, and levels II to V for posterior scalp primaries. Approximate 5-year disease-specific survival (DSS) after treatment was 70% to 75%. Patients with immunosuppression, in particular transplant recipients, are at high risk of developing aggressive metastatic cutaneous SCC. Modifications of the staging systems have demonstrated the prognostic benefits of accurately staging parotid and/or neck nodal disease. PMID- 22076983 TI - Characterization of the reaction path and transition states for RNA transphosphorylation models from theory and experiment. PMID- 22076984 TI - Fluid and mass transport modelling to drive the design of cell-packed hollow fibre bioreactors for tissue engineering applications. AB - A model for fluid and mass transport in a single module of a tissue engineering hollow fibre bioreactor (HFB) is developed. Cells are seeded in alginate throughout the extra-capillary space (ECS), and fluid is pumped through a central lumen to feed the cells and remove waste products. Fluid transport is described using Navier-Stokes or Darcy equations as appropriate; this is overlaid with models of mass transport in the form of advection-diffusion-reaction equations that describe the distribution and uptake/production of nutrients/waste products. The small aspect ratio of a module is exploited and the option of opening an ECS port is explored. By proceeding analytically, operating equations are determined that enable a tissue engineer to prescribe the geometry and operation of the HFB by ensuring the nutrient and waste product concentrations are consistent with a functional cell population. Finally, results for chondrocyte and cardiomyocyte cell populations are presented, typifying two extremes of oxygen uptake rates. PMID- 22076985 TI - Transition zones between healthy and diseased retina in choroideremia (CHM) and Stargardt disease (STGD) as compared to retinitis pigmentosa (RP). AB - PURPOSE: To describe the structural changes across the transition zone (TZ) in choroideremia (CHM) and Stargardt disease (STGD) and to compare these to the TZ in retinitis pigmentosa (RP). METHODS: Frequency-domain (Fd)OCT line scans were obtained from seven patients with CHM, 20 with STGD, and 12 with RP and compared with those of 30 previously studied controls. A computer-aided manual segmentation procedure was used to determine the thicknesses of the outer segment (OS) layer, the outer nuclear layer plus outer plexiform layer (ONL+), the retinal pigment epithelium plus Bruch's membrane (RPE+BM), and the outer retina (OR). RESULTS: The TZ, while consistent within patient groups, showed differences across disease groups. In particular, (1) OS loss occurred before ONL+ loss in CHM and RP, whereas ONL+ loss occurred before OS loss in STGD; (2) ONL+ was preserved over a wider region of the retina in CHM than in RP; (3) RPE+BM remained normal across the RP TZ, but was typically thinned in CHM. In some CHM patients, it was abnormally thin in regions with normal OS and ONL+ thickness. In STGD, RPE+BM was thinned by the end of the TZ; and (4) the disappearances of the IS/OS and OLM were more abrupt in CHM and STGD than in RP. CONCLUSIONS: On fdOCT scans, patients with RP, CHM, and STGD all have a TZ between relatively healthy and severely affected retina. The patterns of changes in the receptor layers are similar within a disease category, but different across categories. The findings suggest that the pattern of progression of each disease is distinct and may offer clues for strategies in the development of future therapies. PMID- 22076986 TI - Differences in baseline dark and the dark-to-light changes in anterior chamber angle parameters in whites and ethnic Chinese. AB - PURPOSE: To assess the anterior chamber drainage angle width in the dark and the dark-to-light change (Delta) between Caucasians and Chinese aged 40 years and older. METHODS: The study groups comprised four age- and sex-matched cohorts: American Caucasians, American Chinese, southern mainland Chinese, and northern mainland Chinese. Anterior segment optical coherence tomography (ASOCT) images of the anterior chamber angles were obtained under both light and dark conditions. The parameters analyzed included angle opening distance (AOD), angle recess area (ARA), and trabecular-iris space area (TISA). RESULTS: Data were obtained from 121, 124, 121, and 120 participants who were American Caucasians, American Chinese, and southern and northern mainland Chinese, respectively. In a multiple linear regression analysis, adjusted for age, sex, refractive status, pupil size, lens location, and anterior chamber depth (ACD) and width (ACW), the ethnic Chinese had significantly smaller ARAs (regression coefficient, beta = -0.06, P < 0.001) and TISAs (beta = -0.01, P = 0.039), as well as greater DeltaAODs (beta = 0.03, P = 0.009) and DeltaTISAs (beta = 0.02, P = 0.029) than did the Caucasians. For the dark-to-light change analysis, the independent associations between angle width and iris thickness (IT) and iris curvature (ICurv) were identified only in the Chinese. CONCLUSIONS: Compared with the Caucasians, the ethnic Chinese had smaller ARA and TISA, but greater dark-to-light changes in AOD and TISA, independent of refractive status and overall ocular anterior segment dimensions. PMID- 22076987 TI - Imaging retrobulbar subarachnoid space around optic nerve by swept-source optical coherence tomography in eyes with pathologic myopia. AB - PURPOSE: To examine the subarachnoid space (SAS) of eyes with pathologic myopia and analyze the characteristics of the SAS and the surrounding tissues by swept source optical coherence tomography (OCT). METHODS: One hundred thirty-three eyes of 76 patients with pathologic myopia (spherical equivalent refractive error of > 8.00 diopters (D) or an axial length >26.5 mm) and 32 eyes of 32 subjects with emmetropia were enrolled. The eyes in both groups were not tested to determine whether glaucoma was present. The papillary and peripapillary areas were examined with a swept-source OCT prototype system that uses a wavelength sweeping laser operated at 100,000 Hz A-scan repetition rate in 1-MUm wavelength. RESULTS: In the B-scan images, the arachnoid trabeculae inside the SAS were clearly observed as a pattern of reticular lines and dots interspersed with hyporeflective zones consistent with fluid, whereas orbital fat had more uniform features with gray intervening spaces. The SAS was triangular, with the base toward the eye surrounding the optic nerve in the region of the scleral flange. An SAS was found in 124 highly myopic eyes (93.2%) but not in the emmetropic eyes. The shortest distance between the inner surface of lamina cribrosa and SAS was 252.4 +/- 110.9 MUm, and the thinnest region of peripapillary sclera above SAS (scleral flange thickness) was 190.6 +/- 51.2 MUm. In one myopic patient, there appeared to be direct communication between the intraocular cavity and SAS through pitlike pores. CONCLUSIONS: Optic SAS is seen in 93% of highly myopic eyes, and the SAS appears to be dilated in highly myopic eyes. The expanded area of exposure to CSF pressure along with thinning of the posterior eye wall may influence staphyloma formation and the way in which certain diseases, such as glaucoma, are manifested. PMID- 22076988 TI - Quantitative mapping of scleral fiber orientation in normal rat eyes. AB - PURPOSE: Previous work has suggested a major role of scleral biomechanics in the pathogenesis of glaucoma. Since fiber orientation in connective tissues is a key determinant of tissue biomechanics, experimental characterization of scleral fiber orientation is needed to fully understand scleral biomechanics. This is a report of baseline experimental measurements of fiber orientation in whole normal rat scleras. METHODS: Twenty ostensibly normal Norway brown rat eyes were fixed in 4% paraformaldehyde. The scleras were cleaned of intra- and extraorbital tissues and dissected into five patches, and each patch was glycerol treated to maximize its transparency. Fiber orientation was measured using small-angle light scattering (SALS). Scattering patterns were analyzed to extract two microstructural parameters at each measurement location-the preferred fiber orientation and the degree of alignment-yielding a fiber orientation map for each sclera. RESULTS: Rat sclera is structurally anisotropic with several consistent features. At the limbus, fibers were highly aligned and organized primarily into a distinct ring surrounding the cornea. In the equatorial region, the fibers were primarily meridionally aligned. In the posterior and peripapillary region, the scleral fibers were mostly circumferential but less aligned than those in the anterior and equatorial regions. CONCLUSIONS: Circumferential scleral fibers may act as reinforcing rings to limit corneal and optic nerve head deformations, whereas equatorial meridional fibers may either provide resistance against extraocular muscle forces or limit globe axial elongation. PMID- 22076989 TI - Prominin-1 localizes to the open rims of outer segment lamellae in Xenopus laevis rod and cone photoreceptors. AB - PURPOSE: Prominin-1 expresses in rod and cone photoreceptors. Mutations in the prominin-1 gene cause retinal degeneration in humans. In this study, the authors investigated the expression and subcellular localization of xlProminin-1 protein, the Xenopus laevis ortholog of prominin-1, in rod and cone photoreceptors of this frog. METHODS: Antibodies specific for xlProminin-1 were generated. Immunoblotting was used to study the expression and posttranslational processing of xlProminin-1 protein. Immunocytochemical light and electron microscopy and transgenesis were used to study the subcellular distribution of xlProminin-1. RESULTS: xlProminin-1 is expressed and is subject to posttranslational proteolytic processing in the retina, brain, and kidney. xlProminin-1 is differently expressed and localized in outer segments of rod and cone photoreceptors of X. laevis. Antibodies specific for the N or C termini of xlProminin-1 labeled the open rims of lamellae of cone outer segments (COS) and the open lamellae at the base of rod outer segments (ROS). By contrast, anti peripherin-2/rds antibody, Xper5A11, labeled the closed rims of cone lamellae adjacent to the ciliary axoneme and the rims of the closed ROS disks. The extent of labeling of the basal ROS by anti-xlProminin-1 antibodies varied with the light cycle in this frog. The entire ROS was also faintly labeled by both antibodies, a result that contrasts with the current notion that prominin-1 localizes only to the basal ROS. CONCLUSIONS: These findings suggest that xlProminin-1 may serve as an anti-fusogenic factor in the regulation of disk morphogenesis and may help to maintain the open lamellar structure of basal ROS and COS disks in X. laevis photoreceptors. PMID- 22076990 TI - Inhibition of hepatitis C virus replication by Monascus pigment derivatives that interfere with viral RNA polymerase activity and the mevalonate biosynthesis pathway. AB - OBJECTIVES: Hepatitis C virus (HCV) infection causes chronic liver disease and is a major public health problem worldwide. The aim of this study was to evaluate the potential of Monascus pigment derivatives, which were derived from a microbial secondary metabolite synthesized from polyketides by Monascus spp., as HCV antiviral agents. METHODS: We performed an in vitro RNA-dependent RNA polymerase (RdRp) assay to screen for HCV RdRp inhibitors. The anti-HCV activity of RdRp inhibitors in HCV-replicating cells was evaluated by quantification of the RNA viral genome. Molecular docking analysis was performed to predict the binding sites of the selected RdRp inhibitors. RESULTS: We have identified a Monascus pigment and its derivatives as inhibitors of the HCV NS5B RdRp. A group of Monascus orange pigment (MOP) amino acid derivatives, in which the reactive oxygen moiety was changed to amino acids, significantly inhibited HCV replication. Further, combination of the MOP derivatives (Phe, Val or Leu conjugates) with interferon (IFN)-alpha inhibited HCV replication more than IFN alpha treatment alone. Lastly, molecular docking studies indicate the inhibitors may bind to a thumb subdomain allosteric site of NS5B. The antiviral activity of the MOP derivatives was related to a modulation of the mevalonate pathway, since the mevalonate-induced increase in HCV replication was suppressed by the MOP compounds. CONCLUSIONS: Our results identify amino acid derivatives of MOP as potential anti-HCV agents and suggest that their combination with IFN-alpha might offer an alternative strategy for the control of HCV replication. PMID- 22076991 TI - A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance--Part 27. PMID- 22077059 TI - Blocking IL-21 signaling ameliorates xenogeneic GVHD induced by human lymphocytes. AB - In rodent graft-versus-host disease (GVHD) models, anti-IL-21 neutralizing mAb treatment ameliorates lethality and is associated with decreases in Th1 cytokine production and gastrointestinal tract injury. GVHD prevention was dependent on the in vivo generation of donor-inducible regulatory T cells (Tregs). To determine whether the IL-21 pathway might be targeted for GVHD prevention, skin and colon samples obtained from patients with no GVHD or grade 2 to 4 GVHD were analyzed for IL-21 protein expression. By immunohistochemistry staining, IL-21 protein-producing cells were present in all gastrointestinal tract samples and 54% of skin samples obtained from GVHD patients but not GVHD-free controls. In a human xenogeneic GVHD model, human IL-21-secreting cells were present in the colon of GVHD recipients and were associated with elevated serum IL-21 levels. A neutralizing anti-human IL-21 mAb given prophylactically significantly reduced GVHD-associated weight loss and mortality, resulting in a concomitant increase in Tregs and a decrease in T cells secreting IFN-gamma or granzyme B. Based on these findings, anti-IL-21 mAb could be considered for GVHD prevention in the clinic. PMID- 22077060 TI - MicroRNA regulation of STAT4 protein expression: rapid and sensitive modulation of IL-12 signaling in human natural killer cells. AB - IL-12 exerts several regulatory effects on natural killer (NK) cells by activating IL-12 signaling. IL-12 signaling is tightly auto-regulated to control its onset and termination, with prolonged IL-12 treatment resulting in IL-12 hyporesponsiveness. However, the mechanisms underlying IL-12 auto-regulation are still unclear. In this study we report that prolonged IL-12 treatment significantly up-regulates microRNAs (miRNAs), including miR-132, -212, and -200a in primary human NK cells. This up-regulation correlates temporally with gradually decreasing STAT4 levels and decreasing IFN-gamma expression, after an initial increase within the first 16 hours of IL-12 treatment. The IL-12 hyporesponsiveness is dependent on IL-12 concentration, and associated up regulation of miR-132, -212, and -200a. Furthermore, IL-12-hyporesponsive cells regain responsiveness of IFN-gamma production 24 hours after IL-12 removal, which correlates with decreases in miR-132, -212, and -200a levels. Overexpression of miR-132, -212, and -200a by transfection into NK cells mimics IL-12 priming, inducing IL-12 hyporesponsiveness, whereas transfection of miR-132, -212, and 200a inhibitors largely abolishes IL-12 induction of IL-12 hyporesponsiveness. These data suggest that miR-132, -212, and -200a up-regulation during prolonged IL-12 treatment, negatively regulates the IL-12 signaling pathway by reducing STAT4 expression in primary human NK cells. PMID- 22077061 TI - DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. AB - DNMT3A mutations are associated with poor prognosis in acute myeloid leukemia (AML), but the stability of this mutation during the clinical course remains unclear. In the present study of 500 patients with de novo AML, DNMT3A mutations were identified in 14% of total patients and in 22.9% of AML patients with normal karyotype. DNMT3A mutations were positively associated with older age, higher WBC and platelet counts, intermediate-risk and normal cytogenetics, FLT3 internal tandem duplication, and NPM1, PTPN11, and IDH2 mutations, but were negatively associated with CEBPA mutations. Multivariate analysis demonstrated that the DNMT3A mutation was an independent poor prognostic factor for overall survival and relapse-free survival in total patients and also in normokaryotype group. A scoring system incorporating the DNMT3A mutation and 8 other prognostic factors, including age, WBC count, cytogenetics, and gene mutations, into survival analysis was very useful in stratifying AML patients into different prognostic groups (P < .001). Sequential study of 138 patients during the clinical course showed that DNMT3A mutations were stable during AML evolution. In conclusion, DNMT3A mutations are associated with distinct clinical and biologic features and poor prognosis in de novo AML patients. Furthermore, the DNMT3A mutation may be a potential biomarker for monitoring of minimal residual disease. PMID- 22077062 TI - Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down regulating Th1 and Th17. AB - Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-gamma deficient and IL-17-deficient mice as donors. Infusion of IFN-gamma(-/-) or IL 17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-beta expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD. PMID- 22077064 TI - Transfusion in the absence of inflammation induces antigen-specific tolerance to murine RBCs. AB - Most human transfusion recipients fail to make detectable alloantibodies to foreign RBC antigens ("nonresponders"). Herein, we use a murine model to test the hypothesis that nonresponders may be immunologically tolerant. FVB mice transfused with RBCs expressing transgenic human glycophorin A (hGPA) antigen in the absence of inflammation produced undetectable levels of anti-hGPA immunoglobulins, unlike those transfused in the presence of polyinosinic:polycytidylic acid-induced inflammation. Mice in the nonresponder group failed to produce anti-hGPA after subsequent transfusions in the presence of polyinosinic:polycytidylic acid, whereas anti-hGPA levels increased in the responder group. This tolerance was antigen specific, because nonresponders to hGPA produced alloantibodies to RBCs that expressed a different transgenic antigen. This tolerance was not an idiosyncrasy of the hGPA antigen nor of the recipient strain, because B10.BR mice transfused with membrane-bound hen egg lysozyme antigen-transgenic RBCs also demonstrated induced nonresponsiveness. These data demonstrate that RBCs transfused in the absence of inflammation can induce tolerance. PMID- 22077065 TI - The health status of the Negro today and in the future. 1967. PMID- 22077063 TI - Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. AB - Analysis of the chronic lymphocytic leukemia (CLL) coding genome has recently disclosed that the NOTCH1 proto-oncogene is recurrently mutated at CLL presentation. Here, we assessed the prognostic role of NOTCH1 mutations in CLL. Two series of newly diagnosed CLL were used as training (n = 309) and validation (n = 230) cohorts. NOTCH1 mutations occurred in 11.0% and 11.3% CLL of the training and validation series, respectively. In the training series, NOTCH1 mutations led to a 3.77-fold increase in the hazard of death and to shorter overall survival (OS; P < .001). Multivariate analysis selected NOTCH1 mutations as an independent predictor of OS after controlling for confounding clinical and biologic variables. The independent prognostic value of NOTCH1 mutations was externally confirmed in the validation series. The poor prognosis conferred by NOTCH1 mutations was attributable, at least in part, to shorter treatment-free survival and higher risk of Richter transformation. Although NOTCH1 mutated patients were devoid of TP53 disruption in more than 90% cases in both training and validation series, the OS predicted by NOTCH1 mutations was similar to that of TP53 mutated/deleted CLL. NOTCH1 mutations are an independent predictor of CLL OS, tend to be mutually exclusive with TP53 abnormalities, and identify cases with a dismal prognosis. PMID- 22077066 TI - Bronchial thermoplasty for severe asthma. AB - Bronchial thermoplasty (BT) is a novel treatment of patients with severe asthma who continue to be symptomatic despite maximal medical treatment. It aims to reduce the smooth muscle mass in the airways by delivering controlled thermal energy to the airway walls during a series of three bronchoscopies. Randomized controlled clinical trials of BT in severe asthma have not been able to show a reduction in airway hyperresponsiveness or change in FEV(1) but have suggested an improvement in quality of life, as well as a reduction in the rate of severe exacerbations, emergency department visits, and days lost from school or work. Strict inclusion and exclusion criteria of these trials resulted in the elimination of patients with severe asthma who experienced more than three exacerbations per year. Therefore, the generalizability of this treatment to the broader severe asthma population still needs to be determined. The short-term adverse events consist primarily of airway inflammation and occasionally more severe events requiring hospitalization. Long-term safety data are evolving and have shown thus far clinical and functional stability up to 5 years after BT treatment. Additional studies on BT are needed to establish accurate phenotyping of positive responders, durability of effect, and long-term safety. PMID- 22077067 TI - DNA methylation in inflammatory genes among children with obstructive sleep apnea. AB - BACKGROUND: Pediatric obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Because not all children with OSA exhibit increased systemic inflammation, genetic and environmental factors may be affecting patterns of DNA methylation in genes subserving inflammatory functions. METHODS: DNA from matched children with OSA with and without high levels of high-sensitivity C-reactive protein (hsCRP) were assessed for DNA methylation levels of 24 inflammatory related genes. Primer-based polymerase chain reaction assays in a case-control setting involving 47 OSA cases and 31 control subjects were conducted to confirm the findings; hsCRP and myeloid-related protein (MRP) 8/14 levels were also assayed. MEASUREMENTS AND MAIN RESULTS: Forkhead box P3 (FOXP3) and interferon regulatory factor 1 (IRF1) showed higher methylation in six children with OSA and high hsCRP levels compared with matched children with OSA and low hsCRP levels (P < 0.05). In the case-control cohort, children with OSA and high CRP levels had higher log FOXP3 DNA methylation levels compared with children with OSA and low CRP levels and control subjects. IRF1 did not exhibit significant differences. FOXP3 DNA methylation levels correlated with hsCRP and MRP 8/14 levels and with apnea-hypopnea index (AHI), BMI z score, and apolipoprotein B levels. A stepwise multiple regression model showed that AHI was independently associated with FOXP3 DNA methylation levels (P < 0.03). CONCLUSIONS: The FOXP3 gene, which regulates expression of T regulatory lymphocytes, is more likely to display increased methylation among children with OSA who exhibit increased systemic inflammatory responses. Thus, epigenetic modifications may constitute an important determinant of inflammatory phenotype in OSA, and FOXP3 DNA methylation levels may provide a potential biomarker for end-organ vulnerability. PMID- 22077068 TI - Neonatal cytokine profile in the airway mucosal lining fluid is skewed by maternal atopy. AB - RATIONALE: Heredity from mother or father may impact differently in complex diseases, such as atopy. Maternal atopy is a stronger risk factor than paternal atopy for the development of atopy in the offspring. We hypothesized that mother's and father's atopy would have a differential imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. OBJECTIVES: To study parental atopic imprinting on the cytokines and chemokines in the upper airway mucosal lining fluid of healthy neonates. METHODS: Eighteen cytokines and chemokines were quantified in nasal mucosal lining fluid in 309 neonates from the novel unselected Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohort. MEASUREMENTS AND MAIN RESULTS: Maternal, but not paternal, atopic status (asthma, hay fever, or eczema with or without sensitization) was associated with general down-regulation of all 18 mediators assessed by principal component analysis (overall P = 0.015). CONCLUSIONS: Maternal atopy, but not paternal atopy, showed a strong linkage with a suppressed mucosal cytokine and chemokine signature in asymptomatic neonates, suggesting imprinting by the maternal milieu in utero or perinatal life. PMID- 22077069 TI - Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension. AB - This perspective highlights advances in the understanding of the role of cellular metabolism in the pathogenesis of pulmonary hypertension. Insights gained in the past 20 years have revealed several similarities between the cellular processes underlying the pulmonary vascular remodeling in pulmonary hypertension and those seen in cancer processes. In line with these insights, there is increasing recognition that abnormal cellular metabolism, notably of aerobic glycolysis (the "Warburg effect"), the potential involvement of hypoxia-inducible factor in this process, and alterations in mitochondrial function, are key elements in the pathogenesis of this disease. The glycolytic shift may underlie the resistance to apoptosis and increased vascular cell proliferation, which are hallmarks of pulmonary hypertension. These investigations have led to novel approaches in the diagnosis and therapy of pulmonary hypertension. PMID- 22077071 TI - Structural mix-n-match reveals molecular secrets of platelets. PMID- 22077070 TI - Vitamin D levels and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study. AB - RATIONALE: Low blood levels of 25-hydroxyvitamin D (25[OH]D) have been associated with a higher risk of respiratory infections in general populations and higher risk of exacerbations of lung disease in people with asthma. We hypothesized that low blood levels of 25(OH)D in patients with chronic obstructive pulmonary disease (COPD) would be associated with an increased risk of acute exacerbations of COPD (AECOPD). OBJECTIVES: To determine if baseline 25(OH)D levels relate to subsequent AECOPD in a cohort of patients at high risk for AECOPD. METHODS: Plasma 25(OH)D was measured at baseline in 973 participants on entry to a 1-year study designed to determine if daily azithromycin decreased the incidence of AECOPD. Relationships between baseline 25(OH)D and AECOPD over 1 year were analyzed with time to first AECOPD as the primary outcome and exacerbation rate as the secondary outcome. MEASUREMENTS AND MAIN RESULTS: In this largely white (85%) sample of North American patients with severe COPD (mean FEV(1) 1.12L; 40% of predicted), mean 25(OH)D was 25.7 +/- 12.8 ng/ml. A total of 33.1% of participants were vitamin D insufficient (>=20 ng/ml but <30 ng/ml); 32% were vitamin D deficient (<20 ng/ml); and 8.4% had severe vitamin D deficiency (<10 ng/ml). Baseline 25(OH)D levels had no relationship to time to first AECOPD or AECOPD rates. CONCLUSIONS: In patients with severe COPD, baseline 25(OH)D levels are not predictive of subsequent AECOPD. Clinical trial registered with www.clinicaltrials.gov (NCT00119860). PMID- 22077072 TI - Anti-CD20: tales of identical twins? PMID- 22077073 TI - SHEARiO, fast lane to oxidized VWF. PMID- 22077074 TI - Brewing blood. PMID- 22077075 TI - Training clinicians to lead. PMID- 22077076 TI - Prescribing bevacizumab off-label contravenes GMC advice. PMID- 22077078 TI - Doctors choosing not to be vaccinated is choosing to do harm. PMID- 22077077 TI - Risk of diabetes from statins may be higher in women. PMID- 22077079 TI - Doctors accepting flu vaccination is the sensible and responsible choice. PMID- 22077080 TI - Flu vaccination prevents nosocomial outbreaks. PMID- 22077081 TI - GPs need support to take on leadership roles. PMID- 22077082 TI - Food allergy information and deriving action levels for use. PMID- 22077083 TI - Clarity is necessary and only three labels may be needed. PMID- 22077084 TI - Deadly legacy of GMC's Southall hearings fiasco. PMID- 22077085 TI - GMC has repeatedly breached its duty of care to Professor Southall. PMID- 22077086 TI - Yes to careful introduction of robot assisted surgery. PMID- 22077087 TI - Trainee doctors may miss out on the robotic revolution. PMID- 22077088 TI - Consultation over children's heart surgery was unfair to Royal Brompton, judge rules. PMID- 22077089 TI - European drug regulator is being investigated by fraud agency. PMID- 22077090 TI - Pathology reports solve "new bowel disease" riddle. PMID- 22077091 TI - Commentary: We came to an overwhelming and uniform opinion that these reports do not show colitis. PMID- 22077092 TI - Commentary: I see no convincing evidence of "enterocolitis," "colitis," or a "unique disease process". PMID- 22077093 TI - Institutional research misconduct. PMID- 22077094 TI - Inkjet printed, high mobility inorganic-oxide field effect transistors processed at room temperature. AB - Printed electronics (PE) represents any electronic devices, components or circuits that can be processed using modern-day printing techniques. Field-effect transistors (FETs) and logics are being printed with intended applications requiring simple circuitry on large, flexible (e.g., polymer) substrates for low cost and disposable electronics. Although organic materials have commonly been chosen for their easy printability and low temperature processability, high quality inorganic oxide-semiconductors are also being considered recently. The intrinsic mobility of the inorganic semiconductors are always by far superior than the organic ones; however, the commonly expressed reservations against the inorganic-based printed electronics are due to major issues, such as high processing temperatures and their incompatibility with solution-processing. Here we show a possibility to circumvent these difficulties and demonstrate a room temperature processed and inkjet printed inorganic-oxide FET where the transistor channel is composed of an interconnected nanoparticle network and a solid polymer electrolyte serves as the dielectric. Even an extremely conservative estimation of the field-effect mobility of such a device yields a value of 0.8 cm(2)/(V s), which is still exceptionally large for a room temperature processed and printed transistor from inorganic materials. PMID- 22077095 TI - Electronic laboratory notebook: the academic point of view. AB - Based on a requirement analysis and alternative design considerations, a platform independent electronic laboratory notebook (ELN) has been developed that specifically targets academic users. Its intuitive design and numerous productivity features motivate chemical researchers and students to record their data electronically. The data are stored in a highly structured form that offers substantial benefits over laboratory notebooks written on paper with regard to data retrieval, data mining, and exchange of results. PMID- 22077096 TI - Frameworks for comparing emissions associated with production, consumption, and international trade. AB - While the problem of climate change is being perceived as increasingly urgent, decision-makers struggle to agree on the distribution of responsibility across countries. In particular, representatives from countries hosting emissions intensive exporting industries have argued that the importers of emissions intensive goods should bear the responsibility, and ensuing penalties. Indeed, international trade and carbon leakage appear to play an increasingly important role in the carbon emissions debate. However, definitions of quantities describing the embodiment of carbon emissions in internationally traded products, and their measurement, have to be sufficiently robust before being able to underpin global policy. In this paper we critically examine a number of emissions accounting concepts, examine whether the ensuing carbon balances are compatible with monetary trade balances, discuss their different interpretations, and highlight implications for policy. In particular, we compare the emissions embodied in bilateral trade (EEBT) method which considers total trade flows with domestic emission intensities, with the multi-regional input-output (MRIO) method which considers trade only into final consumption with global emission intensities. If consumption-based emissions of different countries were to be compared, we would suggest an MRIO approach because of the global emissions coverage inherent in this method. If trade-adjusted emission inventories were to be compared, we would suggest an EEBT approach due to the consistency with a monetary trade balance. PMID- 22077097 TI - Copper-mediated chelation-assisted ortho nitration of (hetero)arenes. AB - A novel copper-mediated chelation-assisted ortho C-H nitration of (hetero)arenes has been developed for the first time, which used dioxygen as terminal oxidant and 1,2,3-TCP as solvent, leading to the synthesis of nitroaromatics with excellent regioselectivity and in good yields. Mechanistic investigations indicate a mechanism involving a four-centered transition state, with simultaneous cleavage of an ortho C-H bond and a N-O bond of the nitrate anion on the 2-arylpyridine-coordinated copper(II) complex. PMID- 22077098 TI - Recurrent refractory Clostridium difficile colitis treated successfully with rifaximin and tigecycline: a case report and review of the literature. AB - Clostridium difficile colitis infection is on the rise and is considerably increasing the duration of hospital stay, as well as healthcare costs. The management of C. difficile colitis has become more challenging with the increasing failure of therapeutic response to metronidazole and oral vancomycin. Tigecycline is a new glycylcycline that has shown in vitro activity against C. difficile. We report herein a case of C. difficile colitis that failed to improve on a combination of metronidazole and oral vancomycin. The patient subsequently developed a surgical abdomen secondary to refractory C. difficile colitis, but was successfully treated with a combination of rifaximin and tigecycline after she refused to undergo surgical treatment. PMID- 22077099 TI - Pbx-dependent regulation of lbx gene expression in developing zebrafish embryos. AB - Ladybird (Lbx) homeodomain transcription factors function in neural and muscle development--roles conserved from Drosophila to vertebrates. Lbx expression in mice specifies neural cell types, including dorsally located interneurons and association neurons, within the neural tube. Little, however, is known about the regulation of vertebrate lbx family genes. Here we describe the expression pattern of three zebrafish ladybird genes via mRNA in situ hybridization. Zebrafish lbx genes are expressed in distinct but overlapping regions within the developing neural tube, with strong expression within the hindbrain and spinal cord. The Hox family of transcription factors, in cooperation with cofactors such as Pbx and Meis, regulate hindbrain segmentation during embryogenesis. We have identified a novel regulatory interaction in which lbx1 genes are strongly downregulated in Pbx-depleted embryos. Further, we have produced a transgenic zebrafish line expressing dTomato and EGFP under the control of an lbx1b enhancer -a useful tool to acertain neuron location, migration, and morphology. Using this transgenic strain, we have identified a minimal neural lbx1b enhancer that contains key regulatory elements for expression of this transcription factor. PMID- 22077100 TI - Structure of the borosilicate zeolite catalyst SSZ-82 solved using 2D-XPD charge flipping. AB - The structure of the calcined borosilicate zeolite catalyst SSZ-82 ([Si(61.3)B(4.7)O(132)], Pmmn, a = 24.2783(4), b = 11.4665(2), and c = 14.1127(3) A) has been solved from X-ray powder diffraction (XPD) data using the recently developed 2D-XPD charge flipping approach. The electron density maps generated with the more conventional powder charge flipping (pCF) algorithm could not be interpreted easily, so this new method, which begins by phasing low-resolution, 2D subsets of the data, was applied. Crystallographic phases were derived for the three main projections ([100], [010], and [001]) by using just the corresponding subsets of reflections (0kl, h0l, and hk0, respectively) from the full set of 3039 extracted intensities. These phases were then imposed on the (otherwise random) starting phases in the application of the pCF algorithm to the full data set. The framework structure, with 11 Si/B atoms in the asymmetric unit and a novel 12-/10-ring 2D channel system, could be seen clearly in the resulting electron density map. This is the first application of the 2D-XPD method to data collected on a material of unknown structure. Rietveld refinement of the structure revealed the positions of the B atoms in the framework and indicated that some water had been readsorbed in the pores. PMID- 22077101 TI - The evolution of the OATP hepatic uptake transport protein family in DMPK sciences: from obscure liver transporters to key determinants of hepatobiliary clearance. AB - Over the last two decades the impact on drug pharmacokinetics of the organic anion transporting polypeptides (OATPs: OATP-1B1, 1B3 and 2B1), expressed on the sinusoidal membrane of the hepatocyte, has been increasingly recognized. OATP mediated uptake into the hepatocyte coupled with subsequent excretion into bile via efflux proteins, such as MRP2, is often referred to as hepatobiliary excretion. OATP transporter proteins can impact some drugs in several ways including pharmacokinetic variability, pharmacodynamic response and drug-drug interactions (DDIs). The impact of transporter mediated hepatic clearance is illustrated with case examples, from the literature and also from the Pfizer portfolio. The currently available in vitro techniques to study the hepatic transporter proteins involved in the hepatobiliary clearance of drugs are reviewed herein along with recent advances in using these in vitro data to predict the human clearance of compounds recognized by hepatic uptake transporters. PMID- 22077103 TI - Effects of the SLCO1B1*15 allele on the pharmacokinetics of pitavastatin. AB - The hepatic uptake of pitavastatin is mediated by carriers, especially OATP1B1, which is encoded by the SLCO1B1 gene. Because the liver is a target organ of pitavastatin, OATP1B1 is responsible for both the pharmacological effects and clearance of pitavastatin. The effects of the SLCO1B1*15 allele on the pharmacokinetics (PK) of pitavastatin were studied. Pitavastatin 2 mg was orally administered to 38 subjects with SLCO1B1*1a/*1b (n = 20), *1b/*15 (n = 13), or *15/*15 (n = 5). After pitavastatin administration, the plasma concentrations of pitavastatin and pitavastatin lactone were assayed for up to 48 h using liquid chromatography-tandem mass spectrometry. In comparison to the SLCO1B1*1a/*1b subjects, only a C(max) was slightly higher in the SLCO1B1*1b/*15 subjects. However, the SLCO1B1*15/*15 subjects had a 1.74-fold higher AUC(inf) (285.5 +/- 14.5 vs. 164.6 +/- 41.3 ng.h/mL; p < 0.001), a 2.21-fold higher C(max) (106.7 +/- 15.1 vs. 48.3 +/- 13.4 ng/mL; p < 0.001), and a 47.3% lower apparent oral clearance (13.1 +/- 3.9 vs. 6.9 +/- 0.4 L/h; p < 0.001) of pitavastatin. For pitavastatin lactone, there were no significant differences in AUC(inf), C(max), t(1/2), and t(max) among the three genotypes. Unlike previous studies, the disposition of pitavastatin exposure was not altered in subjects with the SLCO1B1*1b/*15 genotype, except C(max). However, pitavastatin exposure was significantly increased in subjects with the SLCO1B1*15/*15 genotype due to reduced hepatic absorption. PMID- 22077102 TI - A new methodology for predicting human pharmacokinetics for inhaled drugs from oratracheal pharmacokinetic data in rats. AB - Prediction of pharmacokinetic (PK) profile for inhaled drugs in humans provides valuable information to aid toxicology safety assessment, evaluate the potential for systemic accumulation on multiple dosing and enable an estimate for the clinical plasma assay requirements. The accuracy in prediction of inhaled human PK profiles for seven inhaled drugs or drug candidates (salmeterol, salbutamol, formoterol, fluticasone propionate, budesonide, CP-325366 and UK-432097) was assessed using rat oratracheal solution and dry powder PK data. The prediction methodology incorporates allometric scaling and mean residence time (MRT) principles with a two compartmental PK approach. Across the range of compounds tested, the prediction of human inhaled maximum concentration (C(max)) and MRT was within 2-fold for 5 of the 7 compounds, providing an accuracy of prediction similar to the current methodologies used to predict human oral C(max) from preclinical data ( De Buck et al. 2007 ). Administering as a dry powder formulation slowed the rat lung absorption rate of the least soluble compound (fluticasone propionate), impacting the prediction of C(max) and MRT. This flags the potential for preclinical studies with dry powder formulations to positively influence predictive accuracy, although further studies with low solubility inhaled drugs are required to confirm this. This study illustrates the value of preclinical assessment of PKs following administration to the lung, and provides a viable means of predicting the human PK profile for inhaled drugs. PMID- 22077104 TI - Nephroprotective activity of Macrothelypteris oligophlebia rhizomes ethanol extract. AB - CONTEXT: Macrothelypteris oligophlebia (Bak.) Ching (Thelypteridaceae) is a Chinese herbal medicine used traditionally for the treatment of diseases such as edema, boils, burns, and roundworms. However, research about the nephroprotective potential of this plant is not available. OBJECTIVE: Present study was designed to evaluate the protective effect of ethanol extract of M. oligophlebia rhizomes (EMO) on gentamicin (GM)-induced nephrotoxicity. MATERIALS AND METHODS: Rats were intraperitoneal (i.p.) injected with GM (100 mg/kg) to induce nephrotoxicity and simultaneously EMO (250 and 500 mg/kg) was orally given to GM-treated rats for 8 days. Blood urea nitrogen (BUN), serum creatinine (Cr), malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were evaluated in renal tissues. Histopathological analysis was used for evaluation of the renal damage. RESULTS: Administration with GM induced renal dysfunction in rats. Pre-treatment with EMO (500 mg/kg) significantly decreased the levels of BUN, Cr, MDA and NO (decreased BUN from 12.71 +/- 1.28 to 7.19 +/- 0.23 mmol/l, Cr from 39.77 +/- 5.34 to 19.17 +/- 0.90 MUmol/l, MDA from 5.60 +/- 0.37 to 2.63 +/- 0.24 nmol/ml, and NO from 868.17 +/- 22.67 to 589.51 +/- 8.83 MUmol/ml), and also restored the activities of renal antioxidant enzymes (SOD, CAT, and GSH-Px) (restored SOD from 1.59 +/- 0.17 to 2.94 +/- 0.13 U/mg protein, CAT from 3.22 +/- 0.34 to 10.57 +/- 0.27 U/mg protein, and GSH-Px from 9.11 +/- 1.29 to 20.72 +/- 1.83 U/mg protein). DISCUSSION AND CONCLUSION: Our results suggest that the rhizomes of M. oligophlebia potentially have a protective role in renal tissue against oxidative stress in acute renal failure. PMID- 22077105 TI - Porphyrins fused with unactivated polycyclic aromatic hydrocarbons. AB - A systematic study of the preparation of porphyrins with extended conjugation by meso,beta-fusion with polycyclic aromatic hydrocarbons (PAHs) is reported. The meso-positions of 5,15-unsubstituted porphyrins were readily functionalized with PAHs. Ring fusion using standard Scholl reaction conditions (FeCl(3), dichloromethane) occurs for perylene-substituted porphyrins to give a porphyrin beta,meso annulated with perylene rings (0.7:1 ratio of syn and anti isomers). The naphthalene, pyrene, and coronene derivatives do not react under Scholl conditions but are fused using thermal cyclodehydrogenation at high temperatures, giving mixtures of syn and anti isomers of the meso,beta-fused porphyrins. For pyrenyl-substituted porphyrins, a thermal method gives synthetically acceptable yields (>30%). Absorption spectra of the fused porphyrins undergo a progressive bathochromic shift in a series of naphthyl (lambda(max) = 730 nm), coronenyl (lambda(max) = 780 nm), pyrenyl (lambda(max) = 815 nm), and perylenyl (lambda(max) = 900 nm) annulated porphyrins. Despite being conjugated with unsubstituted fused PAHs, the beta,meso-fused porphyrins are more soluble and processable than the parent nonfused precursors. Pyrenyl-fused porphyrins exhibit strong fluorescence in the near-infrared (NIR) spectral region, with a progressive improvement in luminescent efficiency (up to 13% with lambda(max) = 829 nm) with increasing degree of fusion. Fused pyrenyl-porphyrins have been used as broadband absorption donor materials in photovoltaic cells, leading to devices that show comparatively high photovoltaic efficiencies. PMID- 22077107 TI - Clinical effectiveness of inhaled corticosteroids versus montelukast in children with asthma: prescription patterns and patient adherence as key factors. AB - OBJECTIVES: To examine the real-life effectiveness of inhaled corticosteroids (ICS) versus leukotriene receptor antagonists (LTRA) monotherapy in children with mild or moderate asthma. METHODS: Using medical and drug records, we accrued a cohort of 227 children aged 2-17 years, prescribed daily LTRA or ICS monotherapy. LTRA-treated children were matched on age, gender, and previous acute-care visits in a 1:3 ratio to ICS-treated children. Outcomes included rescue oral corticosteroids, prescription duration and dispensing, acute-care visits, hospital admissions, and beta(2)-agonist use. RESULTS: More ICS- than montelukast treated children had persistent asthma (73 vs. 50%) and fewer had good asthma control (35 vs. 61%) at baseline, suggesting residual confounding by indication. Physician prescriptions covered 62% of the follow-up period for ICS compared to 97% for montelukast (mean group difference [MGD]: -17%, 95% CI: -28%, -7%). In pharmacies, patients claimed 51 vs. 74% of prescribed ICS and montelukast, respectively (MGD = -12% [-20%, -4%]). Consequently, dispensed ICS and montelukast covered 24% and 38% of follow-up period, respectively (MGD = -14% [ 22%, -6%]). No group differences in oral corticosteroids (RR = 1.10 [0.66, 1.84]) and acute-care visits (RR = 1.79 [0.96, 3.34]) were observed. ICS-treated children experienced more hospital admissions (RR = 3.63 [1.20, 11.03]) and needed more frequently rescue beta(2)-agonist use of >=4 doses per week (RR = 2.54 [1.23, 5.23]). CONCLUSIONS: When compared to LTRA, the prescription of ICS monotherapy did not significantly reduce rescue oral corticosteroids or acute care visits and was associated with a higher rate of hospital admission for asthma and rescue beta(2)-agonist use. The findings may be due to paradoxical shorter ICS prescription duration and lower patient adherence, despite more persistent asthma and poorer control than in LTRA-treated children. PMID- 22077108 TI - Wildlife diseases in the Netherlands. PMID- 22077109 TI - Emerging diseases with a and the worldwide impact consequences for veterinary curricula. AB - Summary Emerging infections are being recognized at an alarming rate. In the case of emerging viral infections involving free-ranging wildlife, the intrusion of urban and agricultural enterprises into wildlife habitats appears to be playing a major role in the exchange of infectious agents of domestic to wildlife species and vice-versa. It is important that the veterinary profession prepares itself to respond to the threatening challenges. Creation of a course which addressed the principles of infectious diseases, diagnostic medicine, epidemiology, public health, population medicine and control are all imperative. This paper attempts to address some of the principle subjects matter areas which should be included in the course offering. PMID- 22077106 TI - Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo in the treatment of perennial allergic rhinitis. AB - OBJECTIVE: Bilastine is a non-sedating second-generation H(1) antihistamine with proven efficacy and safety in the treatment of patients with seasonal allergic rhinitis and urticaria. The objective of this study was to demonstrate the efficacy and safety of bilastine in patients with perennial allergic rhinitis (PAR). METHODS: In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, patients with symptomatic PAR (n = 650) from Argentina, Europe, and South Africa received bilastine 20 mg, cetirizine 10 mg, or placebo once daily for 4 weeks. The primary efficacy outcome was the mean area under the curve (AUC) of reflective total 6-symptom scores (rT6SS) from baseline visit to day 28 (D28). Secondary outcome measures included mean AUC of instantaneous total 6-symptom scores (iT6SS), and mean AUCs of reflective and instantaneous total 4 nasal symptom scores (T4NSS) and total 2-ocular symptom scores (T2OSS) from baseline to D28. An open-label extension phase evaluated the safety of bilastine 20 mg administered to patients (n = 513) for one year. RESULTS: In the overall population no significant differences in efficacy outcomes were found between active treatments and placebo. On account of the high placebo response in South Africa, a post-hoc analysis was conducted. This analysis demonstrated that statistically significant differences existed between active treatments and placebo in the mean AUC of rT6SS (p < 0.05) and T4NSS (p < 0.02), respectively, from baseline to D28 visit for the intent-to-treat population in patients from Europe and Argentina, whereas the difference was not statistically significant in South Africa. Whether this is related to differences in the demographic or clinical characteristics of South African patients (they had PAR for longer and reported more severe symptoms) and/or the disease management process compared with their European and Argentinean counterparts warrants further investigation. CONCLUSIONS: A post-hoc analysis indicated that bilastine and cetirizine were similarly effective and more effective than placebo during a 4-week treatment period in patients with PAR. In addition, bilastine was shown to be safe and well tolerated over a 1-year treatment period. CLINICAL TRIAL REGISTRY NUMBER: NCT01127620. PMID- 22077110 TI - Effects of environmental contaminants in wildlife species. PMID- 22077111 TI - Fish diseases and environmental quality. PMID- 22077112 TI - The effect of parasites on wildlife. AB - Summary Populations of animals which live in the wild are regulated by many biotic and abiotic factors. Parasites are one of the biotic factors. Parasites may influence their hosts in different ways. They may cause the death of the host due to a direct lethal effect or an indirect effect. Direct lethal effects may occur if killing is a part of the life cycle of the parasite or if hosts and parasites have not developed an equilibrium. The introduction of hosts or parasites into a new environment with suitable hosts or parasites is an example. Death by parasitism may also be caused by a combination of the emaciating effects of parasites combined with factors such as bad weather conditions, environmental pollution or human handling. Parasites may also influence the behaviour of their hosts. If the hosts are intermediate hosts in the life cycle of the parasites, the alterations in behaviour may make them an easier prey for their predators, the final hosts. Parasites may also influence the reproductive success of the hosts. In this respect the relationship between the red grouse (Lagopus lagopus scoticus) and the caecal nematode Trichostrongylus tenuis has been well worked out. PMID- 22077113 TI - Diseases in wild animals in relation to nature management. PMID- 22077114 TI - Survey of tick related problems in roe deer (capreolus capreolus) in the Netherlands. PMID- 22077115 TI - Leptospirosis in wild animals. PMID- 22077116 TI - Botulism in waterfowl. PMID- 22077117 TI - Veterinary science and nature management. PMID- 22077119 TI - Surgical management of urethral prolapse in girls: 13 years' experience. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Urethral prolapse (UP) is a rare condition, with a suggested incidence of one in 3000. It occurs most often in prepubertal, primarily Black, girls. The underlying cause of this condition remains uncertain, although a lack of oestrogen is thought to have a role, owing to the preponderance of the condition in the prepubertal and postmenopausal age groups. A popular theory is that the problem arises as a consequence of poor attachments between the two layers of smooth muscle surrounding the urethra, combined with episodic increases in intraabdominal pressure. The most common presentation of UP is genital bleeding or a mass. The classical appearance of UP (i.e. the 'doughnut' sign) enables diagnosis to be made easily on clinical grounds alone. Optimum management of UP is less certain, with opinion divided on the merits of conservative therapy vs surgical excision. Conservative therapy aims to reduce mucosal oedema, improve local hygiene and counteract lack of oestrogen by using a combination of any or all of the following: Sitz baths, topical oestrogen cream, antibacterial wash/soap and topical antibiotics. Surgical management of UP involves excision of the prolapsed mucosa circumferentially. Several authors have reported success with surgical excision, but it carries a risk of developing stenosis of the urethral opening. The present study supports previously reported findings by other authors in terms of demographics and clinical presentation. Patient ages ranged from 2 to 15 years and all girls were of Black race. They most commonly presented with a mass (8/21 patients) or bleeding (6/21 patients) and diagnosis was confirmed on clinical examination, although one required a general anaesthetic (GA) to complete the examination. The present study shows that, in mild cases (usually where there is a mass without symptoms), UP can be successfully managed using conservative measures. In our practice, this involves the use of Sitz baths. More importantly, the study shows that in cases with more symptomatic prolapse or with evidence of vascular compromise, there is an alternative to a surgical procedure and its potential complications. We have found reducing the prolapse under a GA to be beneficial. Complete reduction was achieved in 3/7 patients, with no recurrence. The remaining four patients with partial reduction had improvement in symptoms, allowing conservative therapy to continue and resulting in complete or almost complete resolution of prolapse at follow-up. This approach has not been described previously in published literature on UP. OBJECTIVE: To review our experience of managing urethral prolapse (UP) in girls. PATIENTS AND METHODS: A total of 21 girls, all of whom were Black and whose age range was 2-15 years, were diagnosed with UP between 1995 and 2008. Case notes were reviewed for age, symptoms, clinical findings, predisposing factors, management and outcomes. RESULTS: Presenting symptoms were: mass (n= 8), bleeding (n= 6), dysuria/straining at micturition (n= 6), discharge (n= 1) and constipation (n= 1). In all, 13 patients were managed conservatively because their symptoms were mild. Seven patients underwent prolapse reduction under general anaesthetic (GA). In one patient, an examination under anesthesia was done to confirm the diagnosis as bedside examination was not possible. Prolapse reduction was complete in only three patients. Two patients had partial reduction, which resolved over the next 3 months. Two patients continue to have minimal residual prolapse. A causative/precipitating factor was found in only one patient (severe chronic constipation). She had a recurrence 2 years after reduction. There were no other recurrences. CONCLUSIONS: UP in girls can be diagnosed clinically in most cases. Girls with mild symptoms can be managed conservatively. For girls with more significant symptoms, we recommend a simple reduction under GA. This may be curative, or may reduce the prolapse significantly. Surgical excision is almost never required. PMID- 22077120 TI - Estimating updraft velocity components over large spatial scales: contrasting migration strategies of golden eagles and turkey vultures. AB - Soaring birds migrate in massive numbers worldwide. These migrations are complex and dynamic phenomena, strongly influenced by meteorological conditions that produce thermal and orographic uplift as the birds traverse the landscape. Herein we report on how methods were developed to estimate the strength of thermal and orographic uplift using publicly available digital weather and topography datasets at continental scale. We apply these methods to contrast flight strategies of two morphologically similar but behaviourally different species: golden eagle, Aquila chrysaetos, and turkey vulture, Cathartes aura, during autumn migration across eastern North America tracked using GPS tags. We show that turkey vultures nearly exclusively used thermal lift, whereas golden eagles primarily use orographic lift during migration. It has not been shown previously that migration tracks are affected by species-specific specialisation to a particular uplift mode. The methods introduced herein to estimate uplift components and test for differences in weather use can be applied to study movement of any soaring species. PMID- 22077121 TI - Aiming at a moving target: Period fertility and changing reproductive goals. AB - Summary Common sense suggests that changes over time in aggregate period fertility rates should be closely, related to changes in desired completed fertility after controlling for contraceptive failure, and desired spacing and timing; the nature of the relationship is, however, far from clear. This paper shows that when desired completed fertility undergoes swings, like those in the United States in recent decades, the turning points in period fertility will precede those in desired completed fertility by as much as five years and the amplitude of the swings in period fertility will be more than twice as great. Cumulated fertility, on the other hand, will lag behind reproductive goals. Period fertility rates will exceed desired completed fertility when desires are increasing and fall below it when desires are decreasing. These theoretical results help to explain some salient features of the American baby boom and bust. It is also shown that during a demographic transition, period fertility will fall more rapidly than desired completed fertility, and that towards the end of the transition, period fertility will increase. PMID- 22077122 TI - On allocating resources for fertility reduction in developing countries. AB - Summary Substantial resources are currently being devoted in attempts to reduce fertility in developing countries. Can their allocation be made more efficient, i.e. more effective per unit of investment? This is an exploratory attempt to apply benefit-cost analysis to various realistic interventions, as judged by knowledgeable experts in the absence of sound empirical information on such impacts. (Such judgements appear to represent essentially the same sort of judgements as are made by policy-makers in the field). The paper concentrates on the methods by which several such analyses are made and illustrates the difficulties and problems encountered, but it also presents certain findings and conclusions of substance that show what results can be derived. PMID- 22077123 TI - Further evidence on the decline in infant mortality in pre-industrial England: North Shropshire, 1561-1810. AB - Summary There is growing evidence of a substantial decline in infant mortality in England from the late seventeenth century onwards. This trend is examined in detail using data from the parish registers of a group of rural parishes in North Shropshire. A major change in the whole pattern of first-year mortality during the period 1661-1810 is indicated, its main features being an increase in mortality between the ages of six and eleven months, and a marked fall in mortality during the first three months of life. Examination of the seasonal pattern of infant mortality shows very heavy mortality among young infants in the winter, presumably from respiratory causes, during the period before 1700. It is suggested that a fall in the number of deaths from these causes was the main reason for the decline in infant mortality since the late seventeenth century. PMID- 22077124 TI - The hospitals and population growth: The voluntary general hospitals, mortality and local populations in the English provinces in the eighteenth and nineteenth centuries part 2. AB - Summary In the second part of this article the number and nature of hospital cases treated in the light of physical, medical and surgical limitations are examined. Each hospital's records of treatment are summarised and discussed. Whether or not the hospitals were able to tackle successfully some of the major diseases and causes of death and thereby exert a positive influence in reducing mortality rates is then considered. Two main conclusions are drawn. First, that the hospitals had a positive role to play within their patient catchment areas, but that this was insufficient to affect national mortality trends decisively. Secondly, the hospitals' influence was of greater importance before the mid nineteenth century. Despite advances in medical knowledge and techniques, population pressure, overcrowding and the growing incidence of serious cases in hospitals coupled with outbreaks of 'hospital diseases' meant that the results of hospital treatment may have become less impressive. But even then, mortality levels in the hospitals were low and the hospitals did not merit their reputation of being 'gateways to death' or as institutions 'which positively did harm'. PMID- 22077125 TI - Forecasting births in Greater London: An application of the easterlin hypothesis. AB - Summary A model for forecasting fertility is proposed in which an attempt is made to represent the cyclical fluctuations in fertility typical of developed societies. R. A. Easterlin has put forward the hypothesis that relative affluence, i.e. tension between material aspirations and resources, is an important determinant of fertility behaviour. Relative cohort size in turn affects relative affluence, because the size of a cohort influences its competitive position in the labour market. However, predictions based on relative cohort size alone neglect other sources of periodic fluctuations in fertility, such as those arising from generational cycles. A periodic component which expresses fertility variations as a direct function of time is, therefore, included in this model. A time series of age-specific fertility rates and population estimates for England and Wales and for Greater London is used to assess the relationship between fertility, relative cohort size, and the periodic time function. There is evidence of significant cyclic effects and some support for the Easterlin hypothesis in that the fertility of younger age groups is inversely related to the relative size of older cohorts. Projections are made of the future trend in total fertility assuming a continuation of the observed relationship. Use of different assumed periodicities permits the generation of variant projections of fertility. PMID- 22077126 TI - Trends in marriage and divorce in Peninsular Malaysia. AB - Summary Median age at marriage for women has risen sharply for each of the three major ethnic groups - Malays, Chinese and Indians, in Peninsular Malaysia since 1957. The sharpest rise has been recorded for Malays and Indians, whose median age at marriage was barely over 17 in 1957. A shortage of potential husbands in the traditionally sanctioned ages contributed to the rise for Malays and Indians, but was probably not the paramount reason; average age differences between the spouses narrowed, but median age at marriage for men actually rose. During the same period, the previously extremely high divorce rates amongst Malays have fallen sharply, though wide inter-state differences remain. The sharp changes in marriage patterns reflect, and in turn are partly responsible for, far reaching social and economic changes. They have profoundly affected fertility levels and patterns, as well as intra-familial relationships. PMID- 22077127 TI - Social status and fertility: A study of a town and three villages in Northwestern Iran. AB - Summary Studies of the relationship between social status and fertility in developing societies have shown diverse results. This study suggests that such findings result in part from problems in the conceptualization of social stratification and social status. In developing societies such as Iran the differentiation of modern and traditional cultural (and occupational) groups within social classes has resulted in the emergence of a dual hierarchy. Measures of social status must therefore reflect these conceptually distinct hierarchies, rather than be limited to linear scales. Figures from a study in a town and three villages in northwest Iran undertaken in 1973 are analyzed. Findings indicate that for women in towns, as social status increases within both traditional and modern occupational hierarchies (husband's occupation) and as measured by income, education and index of modern items, there is a general and almost monotonic decrease in the number of living children, children ever-born, and ideal number of children, with an increase in age at marriage and contraceptive use. The social and cultural homogeneity of the village sample is reflected in the relatively small variations in fertility-related behaviour and attitudes; however, fertility differences between landed and landless villages appear similar to the pattern found in the urban samples. The differences in the fertility behaviour of village and urban women of similar income and educational status indicate that fertility behaviour is related partially to class and partially to status distinctions between urban and rural communities. PMID- 22077128 TI - Neo-natal mortality in South Asia: The special role of tetanus. AB - Summary First-year mortality in rural Uttar Pradesh is characterized by a predominance (60 per cent) of deaths during the first month of life, of which 66 per cent are reported to be due to tetanus. This pattern is not typical of the historical experience of many developed countries and the current experience of some less developed countries where post-neo-natal mortality predominates. To examine this phenomenon, two causal models of neo-natal mortality (one for tetanus and one for all other diseases) are developed and tested using retrospective survey data from 2000 couples living in rural Uttar Pradesh. Neo natal tetanus mortality is found to be primarily a function of opportunities for exposure to the disease (e.g. lack of antiseptic birth practices, ownership of large animals) rather than of socio-economic status or demographic variables. The importance of examining neo-natal mortality by cause, and the shortcomings inherent in making inferences from the historical experiences of Western nations are emphasized. PMID- 22077129 TI - Lactation and fertility in Rural Bangladesh. AB - Summary Analysis of data from various phases of a study of post-partum amenorrhoea in Bangladesh illustrated good aggregate consistency of response on menstrual status, but less individual consistency on duration of post-partum amenorrhoea. Using life table techniques, the median duration of amenorrhoea was calculated as 19.9 months for women with births between February and September 1974. There were substantial seasonal variations in duration, with the median decreasing from 21.5 months for women with February births to 16.9 months for those with September births. By contrast, the median duration of post-partum amenorrhoea varies by only two months for women in the lowest and highest quartiles of weight and weight for height. The seasonal pattern was similar for all weight groups. PMID- 22077130 TI - Estimating the completeness of death registration. AB - Summary Death registration statistics, even when incomplete, can provide valuable information about mortality. In particular, the age structure of deaths can be used to estimate the completeness of registration, provided that this completeness does not vary substantially with age. Two methods of estimating the completeness of death registration from the distribution of deaths by age are described. The first is derived from stable population theory and requires an estimate of the rate of natural increase of the population, as well as assuming stability. However, the technique can also be used to generate simultaneously estimates of the rate of natural increase and of death registration completeness. The second method which requires two census age distributions and intercensal deaths by age, estimates the relative enumeration completeness of the two censuses as well as the completeness of death registration and requires only that the population be closed. Results are sensitive to overstatement of age. The methods are illustrated by being applied to figures from Thailand for the period 1960-70 and are found to work satisfactorily. PMID- 22077131 TI - Changes in acceptors' and users' ages: A test of an explanatory mechanism. AB - Summary Acceptors in national family planning programmes are becoming steadily younger, with fewer children. In the present analysis, which makes use of the computerized component projection scheme CONVERSE, it is shown that saturation of the older groups with users has a relatively minor role to play in reducing the mean age of new acceptors. Even where acceptance and continuation rates are high and follow the usual pattern of higher levels for the older women, the build-up of users in the upper age groups is not enough to produce major changes in the age of acceptors. Yet acceptor ages have fallen consistently and sharply in most national programmes, regardless of the general strength, duration, or method mix. The finding that the mechanical effects investigated here play rather a small part in the large empirical declines in acceptor ages suggests the need to investigate other explanations. For this, a critical need is more data than are at present available on trends in age-specific rates of acceptance in national programmes. PMID- 22077132 TI - A modification for use in destabilized populations of brass's technique for estimating completeness of death registration. AB - Summary Brass has developed a method of estimating completeness of death registration using only data on deaths and population by age and sex. In this paper, his method is briefly outlined and the assumptions upon which it is based are discussed. In particular, the implications of the failure of the assumption of stability of the population are investigated. It is found that in populations where mortality has been declining, use of the technique leads to underestimation of completeness. A modification of the technique based on knowledge of the duration and rate of mortality change is proposed for use in such populations. Using simulated destabilized populations, the modification is tested and found to yield more accurate estimates of completeness of death registration than the unmodified technique. The usefulness of the modified technique is further illustrated by applying it to data for Costa Rican females in 1963. PMID- 22077133 TI - Fecundability, coital frequency and the viability of Ova. AB - Summary An extension of Barrett and Marshall's model expressing fecundability as a function of coital pattern is proposed. In particular, this extension includes the probability that the ovum remains alive. The extended model has been applied to Barrett and Marshall's data, a series of cycles for which basal body temperature curves and the date of coitus have been recorded. It was thus possible to estimate the daily probabilities of fertilization and, under certain assumptions, the proportion of lost ova. This proportion was estimated to be above 50 per cent, and increases with age. The increase of fecundability with frequency of intercourse is more moderate than that predicted by Barrett and Marshall's model. PMID- 22077136 TI - The association between social phobia, social anxiety cognitions and paranoid symptoms. AB - OBJECTIVE: Previous research suggests high levels of comorbidity between social phobia and paranoid symptoms, although the nature of this association remains unclear. METHOD: Data were derived from the Early Developmental Stages of Psychopathology study, a 10-year longitudinal study in a representative German community sample of 3021 participants aged 14-24 years at baseline. The Munich Composite International Diagnostic Interview was used to assess social phobia and paranoid symptoms, along with data on social phobia features. Cross-sectional and longitudinal analyses were conducted. Differential associations with environmental risk factors and temperamental traits were investigated. RESULTS: Lifetime social phobia and paranoid symptoms were associated with each other cross-sectionally (OR = 1.80, 95% CI = 1.31-2.47). Lifetime paranoid symptoms were associated specifically with social anxiety cognitions. Lifetime cognitions of negative evaluation predicted later onset of paranoid symptoms, whereas onset of social phobia was predicted by cognitions of loss of control and fear/avoidance of social situations. Lifetime social phobia and paranoid symptoms shared temperamental traits of behavioural inhibition, but differed in environmental risks. CONCLUSIONS: The present study showed that paranoid symptoms and social phobia share similarities in cognitive profile and inhibited temperament. Avoidance appears to be important in the development of social phobia, whereas cannabis use and traumatic experiences may drive paranoid thinking in vulnerable individuals. PMID- 22077137 TI - Defective barrier function in melasma skin. AB - BACKGROUND: Melasma is characterized by increased pigmentation and photodamaged features, which include solar elastosis. Recently, we detected the downregulation of the genes most associated with lipid metabolism using microarray analysis in melasma. These findings suggested that lesional skin may have different biophysical characteristics, and, in particular, an altered skin barrier function. OBJECTIVE: To determine the cutaneous biophysical characteristics of melasma. METHODS: The melanin index, erythema index, stratum corneum hydration, sebum content and transepidermal water loss (TEWL) were measured for lesional and perilesional normal skin of 16 melasma patients and then compared. In addition, a skin biopsy was performed on 11 of the 16 study subjects to measure stratum corneum thickness and to study the protein expressions of PPAR-alpha and ALOX15B. RESULTS: Melanin index, erythema index and stratum corneum hydration were significantly higher in lesional skin than in perilesional normal skin. No significant difference was found between lesional and normal skin in terms of basal TEWL level or sebum content. However, the rate of TEWL after barrier perturbation was significantly higher for lesional skin, and the barrier recovery rate was significantly delayed. Furthermore, a trend towards thinned stratum corneum was observed for lesional skin, and this was correlated with barrier recovery rate. The expressions of PPAR-alpha and ALOX15B were variable in the samples. CONCLUSIONS: Melasma skin is characterized by impaired stratum corneum integrity and a delayed barrier recovery rate. PMID- 22077138 TI - Is a new high-voltage lead necessary? 6.6-French ICD lead failure: a UK tertiary center experience. PMID- 22077140 TI - Transcriptional control of HIV replication by multiple modulators and their implication for a novel antiviral therapy. AB - Transcriptional regulation is critical for the human immunodeficiency virus 1 (HIV-1) life cycle and is the only step at which the virus amplifies the content of its genetic information. Numerous known and still unknown transcriptional factors, both host and viral, regulate HIV-1 gene expression and latency. This article is a comprehensive review of transcription factors involved in HIV-1 gene expression and presents the significant implications of nuclear factor kappa B (NF-kappaB) and the HIV-1 transactivator of transcription (Tat) protein. We include recent findings on chromatin remodeling toward HIV transcription and its therapeutic implication is also discussed. The current status of small-molecular weight compounds that affect HIV transcription is also described. PMID- 22077141 TI - Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. AB - OBJECTIVE: To present results from the United States (US) Cluster Headache Survey including data on cluster headache demographics, clinical characteristics, suicidality, diagnostic delay, triggers, and personal burden. BACKGROUND: There are few large-scale studies looking at cluster headache patients and none from the USA. This manuscript will present data from The US Cluster Headache Survey, the largest survey ever completed of cluster headache patients living in the USA. METHODS: The total survey was composed of 187 multiple-choice questions that dealt with issues related to cluster headache including demographics, clinical characteristics, comorbid medical conditions, family history, triggers, smoking history, and personal burden. The survey was placed on a Web site from October through December 2008. RESULTS: A total of 1134 individuals completed the survey (816 male, 318 female). Some key highlights from the survey include the following: (1) diagnostic delay: there remains a significant diagnostic delay for cluster headache patients on average 5+ years with only 21% receiving a correct diagnosis at time of initial presentation. (2) Suicidality: suicidal ideations are substantial, occurring in 55%. (3) Eye color: the predominant eye color in cluster headache patients is brown and blue, not hazel as suggested in previous descriptions. (4) Laterality: cluster headache has a right-sided predominance. (5) Attack profile: in US cluster headache sufferers, most attacks occur between early evening and early morning hours with peak time of headache onset between midnight and 3 am; the circadian periodicity for cluster headache is present but is not as predominant in the population as previously thought. (6) Triggers: beer is the most common type of alcohol trigger in US cluster headache patients; noted migraine triggers such as weather changes and smells are also very common cluster headache triggers. (7) Medical comorbidities: peptic ulcer disease does not have a high prevalence in US cluster headache patients as suggested by previous literature; cluster headache is associated with a low prevalence of cardiac disease as well as cerebrovascular disease even though the majority of patients are chronic heavy smokers. In US cluster headache sufferers, there appears to be comorbidity with restless leg syndrome, and this has not been demonstrated in non US cluster headache populations. (8) Personal burden: cluster headache is disabling to the individual as almost 20% of cluster headache patients have lost a job secondary to cluster headache, while another 8% are out of work or on disability secondary to their headaches. CONCLUSION: Some findings from the US Cluster Headache Survey expound on what is currently known about cluster headache, while some of the results contradict what has been previously written, while other information is completely new about this fascinating headache disorder. PMID- 22077142 TI - Social capital and knowledge sharing: effects on patient safety. AB - AIMS: This article is a report on a study that empirically examines the influence of social capital on knowledge sharing and the impact of knowledge sharing on patient safety. BACKGROUND: Knowledge sharing is linked to many desirable managerial outcomes, including learning and problem-solving, which are essential for patient safety. Rather than studying the tangible effects of rewards, this study examines whether social capital (including social interaction, trust and shared vision) directly supports individual knowledge sharing in an organization. METHODS: This cross-sectional study analysed data collected through a questionnaire survey of nurses from a major medical centre in northern Taiwan. The data were collected over a 9-month period from 2008 to 2009. The data analysis was conducted using the Partial Least Squares Graph v3.0 program to evaluate the measurement properties and the structural relationships specified in the research model. FINDINGS: Based on a large-scale survey, empirical results indicate that Registered Nurses' perceptions of trust and shared vision have statistically significant and direct effects on knowledge sharing. In addition, knowledge sharing is significantly and positively associated with patient safety. CONCLUSION: The findings suggest that hospital administrators should foster group trust and initiate a common vision among Registered Nurses. In addition, administrators and chief knowledge officers of hospitals should encourage positive intentions towards knowledge sharing. PMID- 22077143 TI - An analysis examining socio-economic variations in the provision of NHS general dental practitioner care under a fee for service contract among adolescents: Northern Ireland Longitudinal Study. AB - OBJECTIVES: To examine socio-economic variations in the use of publicly funded general dental practitioner care by adolescents under a fee for service arrangement. METHOD: Publicly funded general practitioner reimbursement data were linked to census and vital statistics data within the Northern Ireland Longitudinal Study. Data relate to 12,846 adolescents aged 11 or 12 in April 2003 included within the Northern Ireland Longitudinal Study (28% of the population). The main outcome measure was consumption of dental care between 2003/2004 and 2007/2008 by socio-economic status (as measured by National Statistics Socio economic Classification of occupation and highest educational attainment of household reference person). RESULTS: In multivariate analysis, socio-economic status was a significant determinant of dental care consumed. Those of the lowest socio-economic status, according to both occupation and highest educational attainment of household reference person, were less likely to have consumed orthodontics OR 0.76 (0.62, 0.95) and OR 0.79 (0.69, 0.91), respectively. Those of lower socio-economic status were, however, more likely to have undergone an extraction and restorative treatment and also consumed on average more treatment than those of higher socio-economic status. CONCLUSION: A demand-led service, in which practitioners are reimbursed in part on a fee for service basis, may create incentives that contribute to different patterns of utilization between social groups. Such a system may not be providing equal access for equal need and may widen existing socio-economic disparities in oral health among adolescents. PMID- 22077139 TI - Climate-induced changes to the ancestral population size of two Patagonian galaxiids: the influence of glacial cycling. AB - Patagonia is one of the few areas in the Southern Hemisphere to have been directly influenced by Quaternary glaciers. In this study, we evaluate the influence that Quaternary glacial ice had on the genetic diversity of two congeneric fish species, the diadromous Galaxias maculatus and the nondiadromous Galaxias platei, using multilocus estimates of effective population size through time. Mid-Quaternary glaciations had far-reaching consequences for both species. Galaxias maculatus and G. platei each experienced severe genetic bottlenecks during the period when Patagonia ice sheet advance reached its maximum positions c. 1.1-0.6 Ma. Concordant drops in effective size during this time suggest that range sizes were under similar constraints. It is therefore unlikely that coastal (brackish/marine) environments served as a significant refuge for G. maculatus during glacial periods. An earlier onset of population declines for G. platei suggests that this species was vulnerable to modest glacial advances. Declines in effective sizes were continuous for both species and lasted into the late Pleistocene. However, G. maculatus exhibited a strong population recovery during the late-Quaternary (c. 400,000 bp). Unusually long and warm interglacials associated with the late-Quaternary may have helped to facilitate a strong population rebound in this primarily coastal species. PMID- 22077145 TI - Two series of multicomponent rare earth (Eu3+, Tb3+, Sm3+) polymeric hybrids: chemically bonded assembly and photophysical properties. AB - In the present work, two new chemical linkages (BPDA-PAM, BPDA-DG) are synthesized through the reaction between 4,4'-biphthalic anhydride (BPDA) and acrylamide (AM), diethylene glycol (DG), respectively. Then two novel series of multicomponent rare earth (Eu(3+), Tb(3+), Sm(3+)) polymeric hybrids have been assembled through the coordination bonding: one is from the linkage BPDA-PAM to form the hybrids BPDA-PAM-RE-phen(bipy) (2,2'-bipyridine (bipy) and 1,10 penanthroline (phen)), the other is from the linkage BPDA-DG to compose the hybrids BPDA-DG-RE-PVP and PVP (PVP = poly vinylpyridine). These hybrids are characterized and especially the photophysical properties (luminescence spectra, lifetimes and quantum efficiencies) are discussed in detail. PMID- 22077146 TI - Pediatric regional anesthesia: abdominal wall blocks. AB - Abdominal wall blocks are an effective regional anesthetic technique to provide sufficient analgesia in abdominal surgery. This article reviews the use of abdominal wall blocks in pediatric regional anesthesia. PMID- 22077147 TI - Restricted joint range of motion in patients with MPS II: correlation with height, age and functional status. AB - AIM: The aims of the study were to assess shoulder range of motion (ROM) in patients with mucopolysaccharidosis type II (MPS II) and to correlate joint mobility with patients' height, age and functional status. METHODS: Passive ROM and Z-score of height were followed in 29 patients with MPS II (mean age 11.5 years, range 2-29 years) between the years 2005 and 2010. Passive ROM was measured by a goniometer, and height, by a stadiometer. Functional status was assessed by an age-appropriate health assessment questionnaire (HAQ). RESULTS: (i) A strong correlation was observed between patients' age and Z-score of patients' height (R = 0.78, p < 0.001). (ii) A medium correlation was observed between Z-score of patients' height and passive shoulder flexion and abduction (R = 0.697, p < 0.001 and R = 0.63, p < 0.001, respectively). The progression of restriction was slower in attenuated patients. (iii) Restrictions in shoulder flexion and abduction were already observed before the second year of life. (iv) ROM limitations intensified and became more severe with age. (v) Activities of daily living depended on cognitive impairment of patients with MPS II. CONCLUSION: Range of motion limitations in patients with MPS II correlate with patients' height, increase with patients' age and are more pronounced in a severe form of MPS II. PMID- 22077148 TI - Lack of association of outcomes with treatment duration and microbiologic susceptibility data in Clostridium difficile infections in a non-NAP1/BI/027 setting. AB - BACKGROUND: Concerns regarding the poor response of severe Clostridium difficile infection (CDI) treated with metronidazole have arisen over the last 5 y. METHODS: We conducted a prospective, non-interventional study of CDI cases at our institution to evaluate the role of drug resistance, co-morbidities, and the emergence of hypervirulent strains on patient outcomes. A total of 118 adult inpatients with diarrhea and a positive stool for C. difficile toxin immunoassay had positive stool cultures and were included in the study. All 118 isolates had vancomycin and metronidazole susceptibility testing via the E-test method; rep PCR was performed on 47 isolates. Of the 118 study patients, 107 were treated with either metronidazole or vancomycin. RESULTS: Initial therapy was metronidazole in 98.1% (n = 105) and vancomycin in 1.9% (n = 2) patients. Evaluable clinical response within 5 days of treatment was noted in 52.5% (52/99) of cases. The mean duration of treatment was 11.7 +/- 7.2 days. The 30-day all cause mortality rate was 24.6% (29/118). Recurrence occurred in 23.6% (21/89). A recent stay in the intensive care unit was associated with increased 30-day mortality (odds ratio 3.58, p = 0.012). There were no isolates resistant to metronidazole or vancomycin. Only 1 isolate was possibly related to the NAP1/BI/027 reference strain. No strain-related differences in deaths or recurrence were noted. CONCLUSIONS: Deaths related to CDI in our study appear to be related to multiple factors and did not appear to be independently related to antibiotic susceptibility, strain type, or treatment duration. PMID- 22077149 TI - Intensity-dependent exciton dynamics of (6,5) single-walled carbon nanotubes: momentum selection rules, diffusion, and nonlinear interactions. AB - The exciton dynamics for an ensemble of individual, suspended (6,5), single walled carbon nanotubes revealed by single color E(22) resonant pump-probe spectroscopy for a wide range of pump fluences are reported. The optically excited initial exciton population ranges from approximately 5 to 120 excitons per ~725 nm nanotube. At the higher fluences of this range, the pump-probe signals are no longer linearly dependent on the pump intensity. A single, predictive model is described that fits all data for two decades of pump fluences and three decades of delay times. The model introduces population loss from the optically active zero momentum E(22) state to the rest of the E(22) subband, which is dark due to momentum selection rules. In the single exciton limit, the E(11) dynamics are well described by a stretched exponential, which is a direct consequence of diffusion quenching from an ensemble of nanotubes of different lengths. The observed change in population relaxation dynamics as a function of increasing pump intensity is attributed to exciton-exciton Auger de-excitation in the E(11) subband and, to a lesser extent, in the E(22) subband. From the fit to the model, an average defect density 1/rho = 150 nm and diffusion constants D(11) = 4 cm(2)/s and D(22) = 0.2 cm(2)/s are determined. PMID- 22077151 TI - Signaling pathways in pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy characterized by a plethora of molecular alterations that include major and minor driving mutations, the presence of intense desmoplasia exhibiting numerous proliferating pancreatic stellate cells (PSC) and cancer-associated fibroblasts that produce fibronectin and collagens, and foci of inflammatory cells that produce mitogenic cytokines. This review will focus on signaling by tyrosine kinase receptors, and the role of transforming growth factor beta in this malignancy is described briefly. Potential for therapeutic interventions will be discussed in relation to specific pathways. PMID- 22077144 TI - Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. AB - BACKGROUND: The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. METHODS: In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated. RESULTS: A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome- 2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P=0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P=0.04). CONCLUSIONS: In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.). PMID- 22077150 TI - Hdac-mediated control of endochondral and intramembranous ossification. AB - Histone deacetylases (Hdacs) remove acetyl groups (CH3CO-) from epsilon-amino groups in lysine residues within histones and other proteins. This posttranslational (de) modification alters protein stability, protein-protein interactions, and chromatin structure. Hdac activity plays important roles in the development of all organs and tissues, including the mineralized skeleton. Bone is a dynamic tissue that forms and regenerates by two processes: endochondral and intramembranous ossification. Chondrocytes and osteoblasts are responsible for producing the extracellular matrices of skeletal tissues. Several Hdacs contribute to the molecular pathways and chromatin changes that regulate tissue specific gene expression during chondrocyte and osteoblast specification, maturation, and terminal differentiation. In this review, we summarize the roles of class I and class II Hdacs in chondrocytes and osteoblasts. The effects of small molecule Hdac inhibitors on the skeleton are also discussed. PMID- 22077152 TI - Inflammatory mediators: tracing links between obesity and osteoarthritis. AB - Osteoarthritis (OA), the most common form of arthritis, is associated with joint malfunction and chronic disability in the aged population. It is a multifactorial disorder to which several factors-such as age, sex, trauma, and obesity contribute significantly. Obesity is one of the most influential but modifiable risk factors because it exerts an increased mechanical stress on the tibiofemoral cartilage. However, the high prevalence of OA in obese individuals in non weightbearing areas, like finger joints, suggests that the link between being overweight and OA lies with factors other than simple biomechanics. An important correlation has been made between obesity and inflammation. Adipose tissues (and the infrapatellar fat pad) play an important role in this context because they are the major source of cytokines, chemokines, and metabolically active mediators called adipokines (or adipocytokines). These metabolic factors are known to possess catabolic and proinflammatory properties and to orchestrate the pathophysiological processes in OA. This review provides information on the relationship between obesity and OA through biomechanical and biochemical factors and highlights the functions of important obesity-related inflammatory products in the initiation and progression of OA. This information will broaden our thinking in identifying the targets for both prevention and intervention for OA. PMID- 22077153 TI - Molecular parameters of head and neck cancer metastasis. AB - Metastasis remains a major cause of mortality in patients with head and neck squamous cell carcinoma (HNSCC). HNSCC patients with metastatic disease have extremely poor prognoses, with an average survival rate of less than a year. Metastasis is an intricate sequential process that requires a discrete population of tumor cells to possess the capacity to intravasate from the primary tumor into systemic circulation, survive in circulation, extravasate at a distant site, and proliferate in a foreign, hostile environment. Literature has accumulated to provide mechanistic insight into several signal transduction pathways, receptor tyrosine kinases (RTKs), signal transducer and activator of transcription 3 (Stat3), Rho GTPases, protein kinase Cepsilon (PKCsepsilon), and nuclear factor kappaB (NF-kappaB), that are involved in mediating a metastatic tumor cell phenotype in HN-SCC. Herein we highlight accrued information regarding the key molecular parameters of HNSCC metastasis. PMID- 22077155 TI - The role of BMP2 signaling in the skeleton. AB - While new roles for the adult skeleton as an endocrine organ continue to emerge, our understanding of how bone homeostasis is maintained is also changing. Here we focus on BMP2, a molecule identified by its ability to induce bone formation at extraskeletal sites. We detail specific roles for BMP2 in the adult skeleton, where it acts to regulate the differentiation of periosteal skeletal progenitors during fracture healing and also mediates osteoblast formation in the bone marrow microenvironment. We highlight two areas of BMP2 biology that deserve further study: the specific signaling pathways used by BMP2 to affect bone formation, and the factors that regulate BMP2 production in the adult skeleton. These activities serve to distinguish BMP2 from other members of the TGF-b/BMP/Activin gene superfamily. PMID- 22077154 TI - The synthesis of C8-aryl purines, nucleosides and phosphoramidites. AB - C8-Aryl purines, their nucleosides, and phosphoramidites has been synthetic targets for more than 60 years. Interest in these compounds stems from their utility as fluorescent markers, they have therapeutic uses, are biomarkers, biomolecular probes, supramolecular building blocks, and for conformational studies. Until recently, the selective arylation of the C8-position of purines has been a challenging task. Several approaches have been explored including building them up from a pyrimidine or selective C8-modification of an unsubstituted purine. Neither of these approaches has proven to have broad scope. The discovery that C8-aryl purine nucleosides can be made via the Suzuki cross coupling reaction has allowed a diverse array of analogues to be prepared and, in turn, the corresponding phosphoramidites. The latter is particularly significant as C8-aryl purine adducts are a major mutation observed from aromatic carcinogens and ready access to C8-aryl phosphoramidites will facilitate the synthesis and study of C8-aryl purine biomarkers and modified oligonucleotides. PMID- 22077156 TI - Understanding the skeletal pathology of type 1 and 2 diabetes mellitus. AB - Diabetes affects over 25 million people and is characterized by hyperglycemia resulting from a lack of insulin or reduced insulin sensitivity. A serious complication of diabetes is the increase in fracture risk observed in both type 1 and type 2 diabetic patients. This review focuses on some of the cellular and mechanistic causes of diabetes-induced fracture risk. Type 1 and type 2 diabetes most likely have unique and overlapping mechanisms of bone loss. While type 1 diabetes is associated with reduced bone mineral density, this is not usually seen in type 2 diabetes. Hyperglycemia, present in both type 1 and 2 diabetes, alters bone matrix proteins such as collagen I through nonenzymatic glycation, which can decrease bone toughness and increase fracture risk even in the absence of bone loss. Diabetes is also associated with increased inflammation and altered adipokine and calcitrophic hormone levels, which further contribute to bone pathophysiology. As medical advances significantly lengthen patient lifespan, exposure to diabetic conditions increases and correspondingly so do disease complications. Further research to identify molecular pathways in diabetes associated bone pathology will provide the basis for therapeutic targets/directions to increase treatment options and improve patient health and well-being. PMID- 22077157 TI - Antioxidant potential and radical-scavenging effects of flavonoids from the leaves of Psidium cattleianum grown in French Polynesia. AB - Psidium cattleianum J. Sabine (Myrtaceae) is a traditional medicinal plant in French Polynesia. The leaves and roots possess many medicinal properties. These effects may be correlated with the presence of antioxidant compounds. Seven flavonoids along with a benzoic acid were isolated from the leaves of P. cattleianum. The compounds indicated strong antioxidant and radical-scavenging activities in ALP, DPPH(.), ABTS(.-) and ORAC assays. This study demonstrates that the leaves of P. cattleianum possess main compounds with interesting antioxidant and radical-scavenging activities, as clarified by four biological assays. Our findings may justify the use of these leaves in the traditional medicine of French Polynesia. Among the total eight known compounds, reynoutrin and luteolin were isolated for the first time from the genus Psidium. PMID- 22077158 TI - Refractory hypotension due to Rogaine(r) (minoxidil) ingestion managed with midodrine. AB - BACKGROUND: Minoxidil (Rogaine(r)) is a direct vasodilator that can cause significant toxicity when ingested. We report a case of ingestion of topical minoxidil [Rogaine(r) (Johnson & Johnson Healthcare Products, Division of McNeil PPC, Inc)] resulting in refractory hypotension that was successfully managed with the oral alpha (1) agonist midodrine. CASE REPORT: A 48-year-old male who ingested an eight ounce bottle of Rogaine(r) presented to the emergency department. The patient presented with a blood pressure of 57/45 mmHg and a pulse of 84 beats per minute. The patient received IV fluids and multiple vasopressors to maintain an adequate mean arterial pressure. Midodrine, an oral alpha (1) vasopressor, was added 10 hours post ingestion and was able to maintain an adequate mean arterial pressure. Over the next two days, midodrine was titrated down as his blood pressure returned to baseline. CONCLUSION: Midodrine may serve as an additional option to treat toxicant induced hypotension. PMID- 22077159 TI - Examining the interrelationship of migraine onset, duration, and time to treatment. AB - OBJECTIVE: The objective of this study is to investigate migraines, both longitudinally and cross-sectionally, to understand the impact that time of treatment has on migraine duration and the patients' return to daily functioning. BACKGROUND: Several studies have explored the relationship between migraine treatment and its impact on migraine duration; however, the interrelationship of migraine onset and impact of treatment timing on migraine resolution is not completely understood. DESIGN/METHODS: Five hundred and nine migraineurs completed 1 online baseline survey and a diary survey after each of their next 3 migraines. All subjects were 18 or older and were employed full time. RESULTS: Migraine episodes treated within 1 hour were significantly shorter on average than those treated after 1 hour (9.1 hours vs 12.3 hours) (P < .05). Over-the counter medication was the most frequently reported first-line treatment (44%) followed by an oral triptan (30%), another prescription medication (14%), and combination therapy (4%). Rescue treatment was reported in 57% of attacks. The majority of over-the-counter (69%) and another prescription (55%) treated attacks required rescue whereas only 39% of first-line triptan attacks required rescue. CONCLUSIONS: Treating migraines early with an oral triptan-containing therapy appears to be a very effective method for reducing migraine duration and preventing the need for additional medication. Our findings also suggest that physicians should spend more time educating patients how to identify migraines early. Understanding the relationship between these key factors will provide insight into appropriate treatment and management of migraines, and more importantly, equip patients with the tools necessary to improve their outcomes and overall impact on functioning. PMID- 22077161 TI - [2]Pseudorotaxanes based on the recognition of cryptands to vinylogous viologens. AB - Host-guest complexation between two crown ether-based cryptands and two vinylogous viologens has been studied. Formation of [2]pseudorotaxanes from a dibenzo-24-crown-8-based cryptand and these vinylogous viologens can be reversibly controlled by adding and removing potassium cation in acetone. Furthermore, the complexation between a bis(m-phenylene)-32-crown-10-based cryptand and a vinylogous viologen exhibits a high association constant, 1.18 * 10(6) M(-1) in acetone, and leads to the formation of a supramolecular poly[2]pseudorotaxane in the solid state. PMID- 22077160 TI - Pinellia ternata agglutinin expression in chloroplasts confers broad spectrum resistance against aphid, whitefly, Lepidopteran insects, bacterial and viral pathogens. AB - Broad spectrum protection against different insects and pathogens requires multigene engineering. However, such broad spectrum protection against biotic stress is provided by a single protein in some medicinal plants. Therefore, tobacco chloroplasts were transformed with the agglutinin gene from Pinellia ternata (pta), a widely cultivated Chinese medicinal herb. Pinellia ternata agglutinin (PTA) was expressed up to 9.2% of total soluble protein in mature leaves. Purified PTA showed similar hemagglutination activity as snowdrop lectin. Artificial diet with purified PTA from transplastomic plants showed marked and broad insecticidal activity. In planta bioassays conducted with T0 or T1 generation PTA lines showed that the growth of aphid Myzus persicae (Sulzer) was reduced by 89%-92% when compared with untransformed (UT) plants. Similarly, the larval survival and total population of whitefly (Bemisia tabaci) on transplastomic lines were reduced by 91%-93% when compared with UT plants. This is indeed the first report of lectin controlling whitefly infestation. When transplastomic PTA leaves were fed to corn earworm (Helicoverpa zea), tobacco budworm (Heliothis virescens) or the beet armyworm (spodoptera exigua), 100% mortality was observed against all these three insects. In planta bioassays revealed Erwinia population to be 10,000-fold higher in control than in PTA lines. Similar results were observed with tobacco mosaic virus (TMV) challenge. Therefore, broad spectrum resistance to homopteran (sap-sucking), Lepidopteran insects as well as anti-bacterial or anti-viral activity observed in PTA lines provides a new option to engineer protection against biotic stress by hyper expression of an unique protein that is naturally present in a medicinal plant. PMID- 22077163 TI - Antidepressant-like effect of extract from Polygala paniculata: involvement of the monoaminergic systems. AB - CONTEXT: Polygala paniculata Linnaeus (Polygalaceae) has shown neuroprotective effects, but there is no report about its antidepressant potential. OBJECTIVE: The antidepressant-like effect of the hydroalcoholic extract from P. paniculata and some of the possible mechanisms involved in this effect were investigated in forced swimming test (FST). MATERIALS AND METHODS: Mice received extract by oral route and were submitted to FST and open-field test. Animals were forced to swim and the total immobility time was registered (6-min period). A reduction in the immobility time is considered an antidepressant-like effect. In order to investigate the involvement of the monoaminergic systems, mice were treated with pharmacological antagonists before administration of the extract. RESULTS: The acute administration of the hydroalcoholic extract from P. paniculata produced an antidepressant-like effect, since it significantly reduced the immobility time in FST (0.01-30 mg/kg) as compared to control group, without changing locomotor activity. Pretreatment of mice with yohimbine (1 mg/kg, i.p., alpha2-adrenoceptor antagonist), propranolol (1 mg/kg, i.p., beta-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., dopamine D1 receptor antagonist) or sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist) prevented the antidepressant-like effect of the extract in FST (30 mg/kg). Moreover, ketanserin (5 mg/kg, i.p., preferential 5 HT(2A) receptor antagonist) enhanced the effect of the extract in FST. DISCUSSION AND CONCLUSION: The results of the present study indicate that the extract from P. paniculata has an antidepressant-like action that is likely mediated by an interaction with the serotonergic (5-HT2A receptors), noradrenergic (alpha2 and beta-receptor) and dopaminergic (D1 and D2 receptors) systems. PMID- 22077164 TI - Ethnobotanical study of medicinal plants used in the management of diabetes mellitus and hypertension in the Central Region of Togo. AB - CONTEXT: The Tem tribe in the Central Region of Togo is a population with an extensive knowledge of medicinal plants. However, little is known about their medical practices, principally the use of plants in the management of diabetes mellitus (DM) and hypertension (HTN). OBJECTIVE: The present study documented the indigenous medicinal plant utilization for the management of DM and HTN in the Togo Central Region. METHODOLOGY: From March to October 2010, 55 traditional healers were interviewed about their knowledge on the use of plants for DM and HTN treatment. RESULTS: The results revealed that 35/55 (63.64%) healers had treated at least one case of DM and/or HTN. They highlighted the use of 64 species belonging to 31 families in the treatment of DM and/or HTN. The most used plants against diabetes were Psidium guajava L. (Myrtaceae), Khaya senegalensis A. Juss. (Meliaceae), Sarcocephalus latifolius (Sm.) E.A. Bruce (Rubiaceae), Annona muricata L. (Annonaceae), Bridelia ferruginea Benth. (Phyllanthaceae), and Securidaca longepedunculata Fresen. (Polygalacae), while Allium sativum L. (Liliaceae) and Parkia biglobosa Benth. (Fabaceae), followed by Khaya senegalensis A. Juss. (Meliaceae), Gardenia ternifolia Schumach. (Rubiaceae), and Persea americana Mill. (Lauraceae) were the most commonly cited as antihypertensive. CONCLUSION: The issue revealed that traditional healers of the above mentioned region have basic knowledge regarding herbal medicine for DM and HTN in comparison with previous published reports. Further pharmacological screening of the identified plants should be conducted to ascertain the effectiveness of these plants. PMID- 22077165 TI - A comparison study between different molecular weight polysaccharides derived from Lentinus edodes and their antioxidant activities in vivo. AB - CONTEXT: Polysaccharide purified Lentinus edodes (Berk.) Sing (Tricholomataceae) has been reported to attenuate oxidative stress in vitro. OBJECTIVE: This study investigated whether polysaccharides from L. edodes with different molecular weight have protective effects against oxidative stress induced by D-galactose (D gal) in vivo, and determined the specific relationship between molecular weight and antioxidant activity. MATERIALS AND METHODS: In the present study, we successfully obtained three purified polysaccharides, coded as LT1, LT2, and LT3, and their molecular weights were 25.5, 306.2, and 605.4 kDa, respectively. The D gal-treated mice received three polysaccharides once daily for 60 days. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the content of malondialdehyde (MDA), and erythrocyte membrane fluidity were measured to evaluate the changes of the antioxidant ability. RESULTS: It was demonstrated that the administration of LT1, LT2, and LT3 could improve the antioxidant status to different levels. Furthermore, LT2 exhibited the highest antioxidant ability among these samples in vivo. Indeed, LT2 significantly decreased the content of MDA in liver (15.91 +/- 0.31 versus 23.79 +/- 1.18 nmol/mg protein for the model group, p < 0.05), enhanced the fluidity of erythrocyte membrane (2.458 +/- 0.023 versus 2.167 +/- 0.024 for the model group, p < 0.05), and increased the activities of SOD (147.19 +/- 4.90 versus 82.26 +/- 5.55 units/mg protein for the model group, p < 0.05) and GSH-Px (310.91 +/- 6.24 versus 243.64 +/- 6.77 units/mg protein for the model group, p < 0.05) in liver. DISCUSSION AND CONCLUSION: The LT2 had a potential to be used as a novel natural antioxidant. PMID- 22077166 TI - Effect of ether- and water-soluble fractions of Carica papaya ethanol extract in experimentally induced hyperlipidemia in rats. AB - CONTEXT: The papaya is the fruit of the plant Carica papaya L. (Caricaceae) used in India. Fruit and latex are both rich in an enzyme called papain. It is used as a folk remedy for contraception and abortion. OBJECTIVE: The present study explored the anti-hyperlipidemic effect of the ether- and water-soluble fractions of C. papaya ethanol extract in olive oil-induced hyperlipidemic rats. The study also involved chromatographic studies of extract and fractions. MATERIALS AND METHODS: Flash chromatography was done for the most active fraction. The extract and fractions were administered orally at doses of 200 and 400 mg/kg body weight in rats. Olive oil (5 mL/kg oral dose) was administered 30 min after treatment. Blood was collected and centrifuged at 3000 rpm for 15-20 min and subjected to biochemical analysis. RESULT: The study dose-dependently inhibited the total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL) level, and significantly increased high-density lipoprotein (HDL) level. Phytochemical screening revealed the presence of fats in the ether fraction, whereas the water fraction revealed the presence of tannins, alkaloids, glycosides. UV lambda(max) was found to be 217 nm with a melting point of 41 degrees C for the isolated component. DISCUSSION AND CONCLUSION: The anti-hyperlipidemic effect was evaluated in olive oil-loaded rats. Acute treatment caused stimulatory effect on HDL level and inhibition in TC and TG elevation induced by olive oil. The extract and water fraction showed protective action by increasing the HDL cholesterol level. PMID- 22077167 TI - Identification, quantification of bioactive constituents, evaluation of antioxidant and in vivo acute toxicity property from the methanol extract of Vernonia cinerea leaf extract. AB - CONTEXT: Vernonia cinerea (L.) Less [Compositae (Asteraceae)] is used traditionally for several medical purposes such as inflammation, pain, fever, and cancer. OBJECTIVES: The present study identified the bioactive constituents in the methanol extract of Vernonia cinerea leaf and evaluated its antioxidant activity and acute toxicity. METHODS: The identification of phytochemicals was accomplished by GC-MS and the major antioxidant phenolic compounds in the extract were quantified by HPTLC analysis. To quantify the essential elements, atomic absorption spectrophotometeric analysis was carried out. Total phenol and flavonoid content was measured by Folin-Ciocalteau reagent and 2% aluminium chloride, respectively. RESULTS: GC-MS analysis identified the presence of 27 phytoconstituents. The predominant phenolic compound in the extract as quantified by HPTLC was gallic acid (1.92 mg/g) followed by rutin (0.705 mg/g), quercetin (0.173 mg/g), caffeic acid (0.082 mg/g) and ferulic acid (0.033 mg/g). The following elements were quantified: Fe (0.050 ppm), Mn (0.022 ppm), Co (0.0180 ppm), Pb (0.029 ppm), Hg (3.885 ppm) and Se (4.5240 ppm). The antioxidant activity of the extract increased with increasing concentration and the correlation (r2) for all in vitro assays were satisfactory. CONCLUSIONS: V. cinerea extract has significant (p < 0.05) antiradical activity. Hence, V. cinerea may have potential medicinal value and can be used in the formulation of pharmacological products for degenerative diseases. PMID- 22077168 TI - Self-assembled aggregates originated from the balance of hydrogen-bonding, electrostatic, and hydrophobic interactions. AB - Rich phase behavior was observed in salt-free cationic and anionic (catanionic) mixtures of a double-tailed surfactant, di(2-ethylhexyl)phosphoric acid (abbreviated as DEHPA), and tetradecyldimethylamine oxide (C(14)DMAO) in water. At a fixed C(14)DMAO concentration, phase transition from L(1) phase to L(alpha) phase occurs with increasing amounts of DEHPA. Moreover, in the L(alpha) phase, with the increase in DEHPA concentration, a gradual transition process from vesicle phase (L(alphav)) to stacked lamellar phase (L(alphal)) was determined by cryo- and FF-TEM observations combining with (2)H NMR measurements. The rheological data show that the viscosity increases with DEHPA amounts for L(alphav) phase samples because of the increase in vesicle density. At a certain molar ratio of DEHPA to C(14)DMAO, i.e., 80:250, the samples are with the highest viscoelasticity, indicating the existence of densely packed vesicles. While for L(alphal) phase samples, with increasing DEHPA amount, a decrease of bilayer curvature was induced, leading to a decrease of viscosity obviously. Compared with general catanionic surfactant mxitures, in addition to the electrostatic interaction of ion pairs, the transition of the microstructures is also ascribed to the formation of the hydrogen bonding (-N(+)-O-H...O-N-) between C(14)DMAO molecules and protonated C(14)DMAOH(+), which induces the growth of aggregates and the decrease of aggregate curvatures. PMID- 22077169 TI - There is no low-level fertility and development trap. AB - Summary The theory of the low-level equilibrium trap asserts that an increase in income stimulates population growth sufficiently so that the additional people 'eat up' the 'surplus' over subsistence, and hence drive the level of income back to subsistence. Originally the theory referred primarily to mortality, but nowadays its application is to fertility. In the long-run equilibrium context in which the theory is ordinarily presented, the fact that the long-run elasticity of fertility with respect to income is negative in less developed countries fatally contradicts the accepted version of the trap. But to give every chance for trap theory to be meaningful, the paper presents a period-by-period analysis, embodying larger-than-observed positive elasticities during the early years and the logically necessary counterbalancing negative elasticities during the later years. These elasticities are combined with consumption and production figures for various age groups to estimate the effect in each year after the windfall, and altogether. The results show that even under assumptions not charitable to the conclusion of this paper, additional children do not even come close to 'eating up' the increase in income which induced their births, so that the trap theory is falsified. PMID- 22077170 TI - Old age security and the utility of children in Rural India. AB - Summary This study investigates old age security as a possible motivation for high fertility, using information gathered by means of questionnaires and participant observation in an Indian village during 1975-76. Results indicated that such motivation may be quite weak, and hence that population policies aimed at lowering the economic value of children through public social security programmes would achieve little. A variety of evidence pointed to the importance of economic assets, mainly land, in assuring security in old age rather than an abundance of sons. Moreover, given a low expectation of life the necessity to provide support to the aged was infrequent, a fact which seemed to be appreciated by the surveyed villagers. PMID- 22077171 TI - Returns to scale to family size - who gains from high fertility? AB - Summary In this paper the hypothesis put forward by J. C. Caldwell in a number of recent articles, including one in this journal is tested, that there are social and economic increasing returns to scale to family size. Using two village samples of household data collected in Bangladesh in 1977, it is shown that there is a statistically significant inverse correlation between adjusted consumption of rice per head and family size. This result holds true when age and size of landholding are taken into account. From this, it is concluded that the hypothesis is not empirically supported by the data from Bangladesh. This result is partially explained by the extreme poverty of the region and the fact that women are exploited in Bangladesh society. PMID- 22077172 TI - Social, cultural, and economic determinants of age at birth of first child in Peninsular Malaysia. AB - Summary In order to unravel the complex set of the determinants of fertility, we suggest that the child-bearing process be separated into a sequence of events and intervals. As the first step in the child-bearing process, age at first birth is a critical variable. Using data from the 1966-67 West Malaysia Family Survey, we formulate and test a model of the cultural, social and economic determinants of the timing of first birth among a sample of mothers, aged 30-44. Social origins, measured by the woman's father's occupation and the woman's birthplace are not important determinants, but education, early work experience, and ethnicity exercise very strong effects on the age at first birth. Age at first marriage mediates much of the effect of background variables, which suggest that there is little use of contraception to plan the first birth interval. The strong effect of ethnicity is consistent with a cultural interpretation, but important qualifications are noted. PMID- 22077173 TI - Fertility and socio-economic status in Rural Bangladesh: Differentials and linkages. AB - Summary Socio-economic differentials in fertility are examined by using data collected from a daily registration system covering over 100,000 persons in rural Bangladesh during the period 1968 to 1970. The findings indicate that fertility was generally higher among women in the higher than in the lower socio-economic groups. Several factors associated with high socio-economic status and their relation with the intermediate variables are discussed as providing the linkages with high fertility. These include, health status, breastfeeding, the enforcement of 'purdah' and migration. PMID- 22077174 TI - On the relationship between household composition and population age distribution. AB - Summary Composition of households by age of head and by age of other household members has recently been presented in a convenient algebraic expression, the household composition matrix. It has been shown that this matrix operates as a linear transformation from the vector of household distribution by age of head to the vector of population age distribution. A further analysis will show that the first row of the matrix may be interpreted as representing a vector of average household fertility rates. If the linear relationship between household and population distributions is fully implemented, then a relationship between household fertility and the size of the youngest age group can be derived. If w is the population age distribution and w (1) is the number of persons in the youngest age group, then: where alpha is the first row of the household composition matrix with its first element eliminated, C is the household composition matrix with its first row and first column eliminated, and Psi is the vector w with its first element, w (1) eliminated. Extension of this result will enable simultaneous projection of population and households, suitable for computer application to conventional five-year age groups. PMID- 22077175 TI - Can fertility be estimated from current pregnancy data? AB - Summary This paper explores the feasibility of estimating fertility from reports on current pregnancies collected in single-round sample surveys. Data from 15 countries in the World Fertility Survey are used to evaluate the possibilities. The results indicate that neither the age pattern of fertility nor the total fertility ratio can be reliably estimated from current pregnancy data. For almost all countries, the total fertility ratio based on recent births is higher than that based on current pregnancies, even when the latter estimate is restricted to higher durations of pregnancy. PMID- 22077176 TI - Fertility and mortality estimation from the Panama Retrospective Demographic Survey, 1976. AB - Summary Data from the Retrospective Demographic Survey of Panama offer a unique opportunity to test a wide range of methods for estimating indirectly basic demographic parameters from inaccurate and incomplete data. Our primary emphasis is to evaluate methods for estimating adult mortality from information on widowhood and orphanhood, though estimates of childhood mortality obtained from information on sibling and child survivorship are assessed as well. The results for most of the estimating procedures are consistent; this finding is encouraging because it lends support to the hypothesis that the techniques can provide good estimates of mortality. Methods which produce results which are inconsistent provide valuable lessons. In particular, methods for providing unconditional estimates of values ofl (x) for adults by combining directly information on childhood mortality and adult mortality are shown to produce estimates which predominantly reflect the level of childhood mortality employed. Furthermore, within-method consistency of estimates appears to be a very poor indicator of reliable performance of the estimating technique or quality of data, since most methods yielded estimates which were internally consistent, though estimates made by different methods could differ considerably. In summary, the analysis indicates a birth rate of around 35 per thousand, a death rate of around 7.5 per thousand, a total fertility ratio of about 4.8, and expectations of life at birth of approximately 59 and 64 years for men and women respectively. PMID- 22077177 TI - Some remarks on the paper by Julia Ericksen et al., 'Fertility patterns and trends among the Old Order Amish'. AB - Abstract At the present time there are very few populations, whose members do not practise contraception at all, or only to a very limited extent, and for whom accurate data on nuptiality and fertility exist. Among populations of European residence or origin, there are only a few groups who reject any limitation of families for religious reasons. One of these, the Hutterites, has already been studied; the other, the Old Order Amish, is studied in Ericksen's papers, and my preceding remarks point to the importance of this study. PMID- 22077178 TI - Response to louis Henry. AB - Abstract We have responded to Monsieur Henry's comments in the order in which he presents them. PMID- 22077182 TI - Errata. PMID- 22077179 TI - On Das Gupta's 'Birth function in a two-sex model'. AB - Abstract I have read with great interest Das Gupta's(1) critique of my approach(2) towards the development of a two sex-model. To set the records straight, I must state that his criticisms are not well founded due to the following reasons: PMID- 22077183 TI - Testing tubewell platform color as a rapid screening tool for arsenic and manganese in drinking water wells. AB - A low-cost rapid screening tool for arsenic (As) and manganese (Mn) in groundwater is urgently needed to formulate mitigation policies for sustainable drinking water supply. This study attempts to make statistical comparison between tubewell (TW) platform color and the level of As and Mn concentration in groundwater extracted from the respective TW (n = 423), to validate platform color as a screening tool for As and Mn in groundwater. The result shows that a black colored platform with 73% certainty indicates that well water is safe from As, while with 84% certainty a red colored platform indicates that well water is enriched with As, compared to WHO drinking water guideline of 10 MUg/L. With this guideline the efficiency, sensitivity, and specificity of the tool are 79%, 77%, and 81%, respectively. However, the certainty values become 93% and 38%, respectively, for black and red colored platforms at 50 MUg/L, the drinking water standards for India and Bangladesh. The respective efficiency, sensitivity, and specificity are 65%, 85%, and 59%. Similarly for Mn, black and red colored platform with 78% and 64% certainty, respectively, indicates that well water is either enriched or free from Mn at the Indian national drinking water standard of 300 MUg/L. With this guideline the efficiency, sensitivity, and specificity of the tool are 71%, 67%, and 76%, respectively. Thus, this study demonstrates that TW platform color can be potentially used as an initial screening tool for identifying TWs with elevated dissolved As and Mn, to make further rigorous groundwater testing more intensive and implement mitigation options for safe drinking water supplies. PMID- 22077185 TI - European veterinary dissertations. PMID- 22077184 TI - Examining the effect of the dipole moment on charge separation in donor-acceptor polymers for organic photovoltaic applications. AB - A new low band gap copolymer PBB3 containing [6,6']bi[thieno[3,4-b]thiophenyl] 2,2'-dicarboxylic acid bis-(2-butyloctyl) ester (BTT) and 4,8-bis(2 butyloctyl)benzo[1,2-b:4,5-b']dithiophene (BDT) units was synthesized and tested for solar cell efficiency. PBB3 showed a broad absorbance in the near-IR region with a substantially red-shifted (by more than 100 nm) lambda(max) at 790 nm as compared to the PTB series of polymers, which have been previously reported. The PBB3 polymer also showed both a favorable energy level match with PCBM (with a LUMO energy level of -3.29 eV) and a favorable film domain morphology as evidenced by TEM images. Despite these seemingly optimal parameters, a bulk heterojunction (BHJ) photovoltaic device fabricated from a blend of PBB3 and PC(71)BM showed an overall power conversion efficiency (PCE) of only 2.04% under AM 1.5G/100 mW cm(-2). The transient absorption spectra of PBB3 showed the absence of cationic and pseudo charge transfer states that were observed previously in the PTB series polymers, which were also composed of alternating thienothiophene (TT) and BDT units. We compared the spectral features and electronic density distribution of PBB3 with those of PTB2, PTB7, and PTBF2. While PTB2 and PTB7 have substantial charge transfer characteristics and also relatively large local internal dipoles through BDT to TT moieties, PTBF2 and PBB3 have minimized internal dipole moments due to the presence of two adjacent TT units (or two opposing fluorine atoms in PTBF2) with opposite orientations or internal dipoles. PBB3 showed a long-lived excitonic state and the slowest electron transfer dynamics of the series of polymers, as well as the fastest recombination rate of the charge-separated (CS) species, indicating that electrons and holes are more tightly bound in these species. Consequently, substantially lower degrees of charge separation were observed in both PBB3 and PTBF2. These results show that not only the energetics but also the internal dipole moment along the polymer chain may be critical in maintaining the pseudocharge transfer characteristics of these systems, which were shown to be partially responsible for the high PCE device made from the PTB series of low band gap copolymers. PMID- 22077186 TI - Serum soluble CD26 levels: diagnostic efficiency for atopic dermatitis, cutaneous T-cell lymphoma and psoriasis in combination with serum thymus and activation regulated chemokine levels. AB - BACKGROUND: CD26 is a multifunctional type II transmembrane glycoprotein, which also exists as a secreted isoform, soluble CD26 (sCD26). The CD26 expression on circulating T cells is decreased in some skin diseases such as cutaneous T-cell lymphoma (CTCL) and psoriasis. It remains to be determined whether sCD26 can be used as a marker of skin diseases or not. OBJECTIVE: To investigate utility of sCD26 as a diagnostic marker of skin diseases in combination with thymus and activation-regulated chemokine (TARC). METHODS: Serum sCD26 levels were measured using enzyme-linked immunosorbent assay in 130 participants including 32 patients with atopic dermatitis (AD); 45 patients with CTCL; 26 patients with psoriasis; and 27 healthy controls. RESULTS: Serum sCD26 levels in patients with CTCL and psoriasis (162.1 +/- 80.2 ng/mL and 125.4 +/- 82.1 ng/mL respectively) were significantly lower than those of healthy controls (392.6 +/- 198.7 ng/mL; P < 0.01 and 0.01 respectively). In patients with CTCL, serum sCD26 levels of patients with advanced stage were 135.0 +/- 51.5 ng/mL and they were significantly lower than those with early stage (193.1 +/- 96.0 ng/mL; P < 0.05). When we used serum sCD26 and TARC levels for diagnostic criteria, sensitivity, specificity, positive predictive value and negative predictive value for AD, CTCL and psoriasis were 65.2-73.7%, 81.4-97.6%, 65.2-94.4%, and 81.4-88.9% respectively. CONCLUSION: Serum sCD26 levels, combined with serum TARC levels, are helpful in diagnosis of AD, CTCL and psoriasis. PMID- 22077187 TI - Sex differences in newborn interaction with mother or father during skin-to-skin contact after Caesarean section. AB - AIM: To investigate differences between the breast-seeking and crying behaviour of girls and boys in skin-to-skin contact (SSC) with their mother or their father after Caesarean section as well as the point-in-time for the first breastfeeding and to compare mothers' and fathers' interactive behaviour with their newborn girl or boy. METHODS: Twenty girls and 17 boys were randomized to 25 min of SSC with one or the other parent immediately after birth. The interaction was videotaped. RESULTS: Girls started rooting movements earlier than boys in SSC with either parent (p = 0.027). Infants started to breastfeed significantly earlier if having been in SSC with mothers compared with SSC with fathers during the first 5-30 min (p = 0.018). Girls cried more than boys in SSC with either parent (p = 0.02). Mothers used more touching behaviour towards their newborn infant than fathers (p = 0.001). Mothers touched girls less than boys (p = 0.038). Fathers directed less speech towards girls compared with boys (p = 0.042). CONCLUSION: Early mother-infant SSC immediately after Caesarean section should be promoted until the occurrence of the first breastfeed. If the mother is unable to provide SSC immediately after birth, the father-infant SSC is a valuable alternative because it enhances paternal interaction. PMID- 22077188 TI - Influence of initial strain on the force decay of currently available elastic chains over time. AB - OBJECTIVE: To investigate the dependence of force decay on the initial strain applied to currently available elastic chains. MATERIALS AND METHODS: Eight different elastic chains from eight major companies were tested for force decay over a period of 3 weeks at 50% and 100% strain. They were stored in water and thermocycled between 5 degrees C and 55 degrees C. An Instron 3344 was used for the force measurements. RESULTS: Absolute force values at 50% strain varied between 2.3 N and 4.1 N initially, and between 0.9 N and 1.6 N after 21 days. Thus, the force decay of the elastic chains varied from 37% to 75%. At 100% strain, the force values varied between 2.9 N and 4.7 N initially, and between 1.3 N and 2.1 N after 21 days of continuous strain. The force decay varied between 39% and 67%. Most force decays between 24 hours and 21 days were not significant. This information should be taken into consideration when the appropriate elastic chain is selected for clinical use. CONCLUSION: A wide array of elastic chains with various force levels is available. However, differences between products of greater than 100% were measured for force decay over time. PMID- 22077189 TI - Effect of 10% papain gel on enamel deproteinization before bonding procedure. AB - OBJECTIVE: To test the null hypothesis that enamel deproteinization with 10% papain gel does not increase the shear bond strength of orthodontic brackets bonded with resin-modified glass ionomer cement (RMGIC). MATERIALS AND METHODS: One hundred and twenty bovine incisors were used and divided into eight groups: 1) Transbond XT according to the manufacturer's recommendations, 2) Transbond XT deproteinized with 10% papain gel, 3) RMGIC without enamel deproteinization and without etching, 4) RMGIC without enamel etching and with deproteinization with 10% papain gel, 5) RMGIC deproteinized with 10% papain gel and etched with polyacrylic acid, 6) RMGIC deproteinized with 10% papain gel and etched with phosphoric acid, 7) RMGIC deproteinized with 2.5% sodium hypochlorite, and 8) RMGIC etched with polyacrylic acid. After bonding, the mechanical tests were performed in a Universal mechanical test machine. The values obtained were submitted to an analysis of variance and afterward to the Tukey test (P < .05). RESULTS: It was demonstrated that group 2 presented the highest shear bond strength value, and this differed statistically from the others; group 3 presented the lowest value and showed no differences from groups 4, 5, 7, and 8. Regarding the Adhesive Remnant Index, groups 2 and 6 presented the best results and groups 3 and 8 the worst. It could be concluded that enamel deproteinization with 10% papain gel increases the shear bond strength, irrespective of the etching agent. CONCLUSIONS: The hypothesis is rejected. Papain gel was shown to be a new ally in the orthodontic clinic. PMID- 22077190 TI - Evaluation of palatal bone density in adults and adolescents for application of skeletal anchorage devices. AB - OBJECTIVES: To measure the cortical and cancellous bone densities of the palatal area in adolescents and adults and to compare bone quality among placement sites of temporary anchorage devices. MATERIALS AND METHODS: One hundred twenty cone beam computerized tomography scans were obtained from 60 adolescents (mean age, 12.2 +/- 1.9 years) and 60 adults (24.7 +/- 4.9 years). The measurements of palatal bone density were made in Hounsfield units (HU) at 72 sites at the intersections of eight mediolateral and nine anterioposterior reference lines using InVivoDental software. Repeated-measures analysis of variance was used to analyze intragroup and intergroup differences. RESULTS: The cortical and cancellous bone densities in the adults (816 and 154 HU, respectively) were significantly higher than those in the adolescents (606 and 135 HU; P < .001 and P = .032, respectively). However, the anterior portion of the cortical bone in adolescents had similar density values to the posterior portion of the cortical bone in adults. Gender comparison revealed that females had greater cortical bone densities (769 HU) than their male counterparts did (654 HU; P < .001). CONCLUSIONS: Palatal bone densities were significantly higher in adults than in adolescents, and the anterior palatal areas of adolescents were of similar values to those at the posterior palate of adults. PMID- 22077191 TI - Kin encounter rate and inbreeding avoidance in canids. AB - Mating with close kin can lead to inbreeding depression through the expression of recessive deleterious alleles and loss of heterozygosity. Mate selection may be affected by kin encounter rate, and inbreeding avoidance may not be uniform but associated with age and social system. Specifically, selection for kin recognition and inbreeding avoidance may be more developed in species that live in family groups or breed cooperatively. To test this hypothesis, we compared kin encounter rate and the proportion of related breeding pairs in noninbred and highly inbred canid populations. The chance of randomly encountering a full sib ranged between 1-8% and 20-22% in noninbred and inbred canid populations, respectively. We show that regardless of encounter rate, outside natal groups mates were selected independent of relatedness. Within natal groups, there was a significant avoidance of mating with a relative. Lack of discrimination against mating with close relatives outside packs suggests that the rate of inbreeding in canids is related to the proximity of close relatives, which could explain the high degree of inbreeding depression observed in some populations. The idea that kin encounter rate and social organization can explain the lack of inbreeding avoidance in some species is intriguing and may have implications for the management of populations at risk. PMID- 22077193 TI - Influence of application amount on sunscreen photodegradation in in vitro sun protection factor evaluation: proposal of a skin-mimicking substrate. AB - Widely used polymethylmethacrylate substrates for in vitro sun protection factor (SPF) testing of sunscreens do not mimic the rough surface structure of skin, and in addition, sample loading is less than that used in in vivo SPF testing (2.00 mg cm(-2)). We have developed a skin-mimicking substrate (SMS), which has furrows and ridges on its surface, like human skin. A comparison of the photodegradation profiles of sunscreens on commercially available substrates (including SMS) at the recommended application amounts, and on SMS at various application amounts showed that the photodegradation rate of photounstable sunscreen was dependent on the application amount being higher at lower application amounts. SMS at the recommended application amount of 2.00 mg cm(-2) provided in vitro SPF values that were comparable with in vivo SPF values. Our results confirm that, in order to develop a reliable in vitro SPF method, which is consistent with in vivo SPF determination, it is important to use the same application amount of sample as in the in vivo method, in order to take proper account of sunscreen photostability. PMID- 22077194 TI - Cardiovascular implantable electronic device replacement infections and prevention: results from the REPLACE Registry. AB - BACKGROUND: Infection following cardiovascular implantable electronic device (CIED) replacement is a serious complication, and rates of infection have increased. Analysis of procedural and clinical data from device replacement procedures collected by the REPLACE Registry may provide insights into infection prevention strategies and outcomes. METHODS: We prospectively evaluated procedural complications in patients undergoing CIED replacement over 6 months from 72 U.S. sites. Major and minor infections were predefined and adjudicated by an independent blinded clinical events committee. Data regarding infection prevention strategies and infectious outcomes were analyzed for their potential relationships. RESULTS: A total of 1,744 patients were included in REPLACE. All patients received preoperative intravenous antibiotics and 68.7% received postoperative systemic antibiotic therapy. CIED infection developed in 22 patients (1.3%), of which 14 cases were major (0.8%, 95% confidence interval [CI] 0.4%-1.3%) and eight were minor (0.5%, 95% CI 0.2%-0.9%). Patients with infections were more likely to have had postoperative hematomas (five of 22 [22.7%] vs 17 of 1,722 [0.98%], P = 0.002). Participating sites experiencing infection rates >5% were more likely to use povidone-iodine for topical antisepsis, had lower implantation volume, and had patients with higher Charlson Comorbidity Index (2.79 vs 2.32, 95% CI for difference 0.08-0.86, P = 0.019). CONCLUSIONS: In this multicenter prospective study with 6 months of follow-up, infections associated with CIED replacements were surprisingly infrequent, possibly due to the use of preoperative antibiotics. Patients with infections were more likely to have had a postoperative hematoma, and sites with higher infection rates had sicker patients and lower overall procedural volume. PMID- 22077196 TI - The conformations of cyclooctene: consequences for epoxidation chemistry. AB - The conformational space of cyclooctene has been explored computationally in order to rationalize its high epoxidation selectivity. Four different conformations were identified. Each conformation is chiral and has two enantiomeric forms. The degeneracy is further increased by a ring-inversion process, yielding a total of 16 conformers. The potential energy surface for the interconversion of these conformers was characterized via intrinsic reaction coordinate analyses. Furthermore, an evaluation of the microcanonical partition functions allowed for a quantification of the entropy contributions and hence the calculation of the equilibrium composition at different temperatures. The results strongly suggest that the high epoxidation selectivity, typically observed for cyclooctene, is related to a poor sigma(C-alphaH)-pi(C?C) orbital overlap in the predominant conformation, disfavoring alphaH-abstraction by radical species and thus allylic byproduct formation via undesired homolytic side-reactions. PMID- 22077195 TI - Clinical efficacy of macrolide antibiotics against genetically determined macrolide-resistant Mycoplasma pneumoniae pneumonia in paediatric patients. AB - BACKGROUND AND OBJECTIVE: Since 2000, the prevalence of macrolide-resistant (MR) Mycoplasma pneumoniae has increased among paediatric patients in Japan. To determine the efficacy of macrolides against MR M. pneumoniae pneumonia, microbiological and clinical efficacies were compared during the antibiotic treatment. METHODS: Samples from a total of 30 children with M. pneumoniae pneumonia, as confirmed by PCR and serology, were analyzed. Primers for domain V of 23S rRNA were used, and DNA sequences of the PCR products were compared with the sequence of an M. pneumoniae reference strain. RESULTS: Isolates from 21 patients demonstrated point mutations, and these patients were defined as MR. The remaining nine patients, whose isolates showed no point mutations, were categorized as control (macrolide-sensitive) patients. The number of M. pneumoniae in nasopharyngeal samples from the control group decreased rapidly 48 h after initiation of macrolide treatment and showed a close relationship with clinical outcome. In contrast, the number of M. pneumoniae 48 h after initiation of macrolide treatment were significantly higher in samples from MR patients than in samples from macrolide-sensitive patients. In 15 of 21 MR patients, fever persisted for more than 48 h after the initiation of macrolide treatment. When treatment was changed to minocycline, fever disappeared within 48 h in all these MR patients. There were no differences between MR patients who demonstrated a reduction in fever and those in whom fever persisted after 48 h of macrolide treatment. CONCLUSIONS: The microbiological and clinical efficacies of macrolides for treating patients with MR M. pneumoniae pneumonia were low. These results show that macrolides are clearly less effective in patients with MR M. pneumoniae pneumonia. PMID- 22077197 TI - Evaluation of the clinical safety and efficacy of a newly developed 308-nm excimer lamp for vitiligo vulgaris. PMID- 22077198 TI - In vivo sustained release of siRNA from solid lipid nanoparticles. AB - Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with a challenge of being delivered in a sustained manner. Nanoparticle drug delivery systems allow for incorporating and controlled release of therapeutic payloads. We demonstrate that solid lipid nanoparticles can incorporate and provide sustained release of siRNA. Tristearin solid lipid nanoparticles, made by nanoprecipitation, were loaded with siRNA (4.4-5.5 wt % loading ratio) using a hydrophobic ion pairing approach that employs the cationic lipid DOTAP. Intradermal injection of these nanocarriers in mouse footpads resulted in prolonged siRNA release over a period of 10-13 days. In vitro cell studies showed that the released siRNA retained its activity. Nanoparticles developed in this study offer an alternative approach to polymeric nanoparticles for encapsulation and sustained delivery of siRNA with the advantage of being prepared from physiologically well-tolerated materials. PMID- 22077199 TI - Interictal type 1 cannabinoid receptor binding is increased in female migraine patients. AB - OBJECTIVE: To compare binding of the type 1 cannabinoid receptor (CB1R) between migraine patients and healthy volunteers. BACKGROUND: It has been suggested that endocannabinoid deficiency may play a role in the pathophysiology of migraine. Nonetheless, biochemical studies substantiating this idea remain scarce and are faced with methodological shortcomings partly because of the difficulty to perform measurements of endocannabinoids within the central nervous system itself. METHODS: An observational cross-sectional study was conducted in 20 female migraine patients and 18 healthy women matched for age and body mass index. Positron emission tomography acquisition was performed 90 minutes after intravenous injection of the radioligand [(18)F]MK-9470 to assess binding of [(18)F]MK-9470 to CB1R. RESULTS: Binding of CB1 R was globally increased in migraine patients vs healthy controls (average gray matter difference +16%; P = .009, 2-sample 2-sided Student's t-test). There were no correlations between CB1R binding and any predefined migraine characteristics. Increases in CB1R binding were most pronounced in the anterior cingulate, mesial temporal, prefrontal, and superior frontal cortices. CONCLUSION: The increased interictal CB1R binding, especially in brain regions that exert top-down influences to modulate pain, supports the idea that endocannibinoid deficiency is present in female patients suffering from episodic migraine. PMID- 22077200 TI - Bacteria and pH-sensitive polysaccharide-polymer films for colon targeted delivery. AB - The colon provides drug delivery opportunities for colon-specific and systemic delivery of various therapeutic agents. Different strategies have been utilized in targeting drugs to the colon. Recently, integrated systems which incorporate dual mechanisms in colon targeted delivery have received a lot of attention. Of particular interest is bacteria-aided biomaterials and pH-sensitive polymeric film (BPSF) coating for colon targeted drug delivery. The major constituents of these films are polysaccharides and pH-sensitive polymers. The pH-sensitive polymer retards drug release in the stomach and small intestine, while the polysaccharide is digested by colonic enzymes. Digestion of the polysaccharides by bacterial glycosidic enzymes increases the pore density in the film to facilitate drug release. Generally, bacteria-aided biomaterials and pH-sensitive films can be applied to the delivery of most small organic molecules to the colon. The review encompasses the pharmaceutical design parameters such as film digestibility, swelling index and dry mass loss (that provide molecular mechanistic analysis of film permeability) as well as tensile strength, elastic modulus, and elongation at break (that describe the desirable mechanical properties of the films). A critical analysis of formulation, techniques for characterization of film properties and drug-release kinetics from these systems are emphasized. PMID- 22077201 TI - Nanosuspensions in drug delivery: recent advances, patent scenarios, and commercialization aspects. AB - The interest in the preparation and application of nanometer-sized materials is increasing due to their tremendous potential as a drug delivery system with wide range of applications. Recently, nanoscale systems have received much interest as a way to resolve solubility issues because of their cost-effectiveness and technical simplicity compared to liposomes and other colloidal drug carriers. Nanosuspensions have proven to be a better alternative over other approaches currently available for improving bioavailability of number of drugs with low solubility. Nanosuspensions have been extensively developed for a wide range of drugs and have been evaluated for in vitro and in vivo applications by various routes: parenteral, oral, pulmonary, topical. They have also been used for drug targeting. Different preparation methods for nanosuspensions and their application are being reported and patented. In fact, the number of products based on nanosuspension in the market and under clinical study is higher than that of other nanotechnology-based applications. This article reviews the research and recent advances in formulation, characterization, application of nanosuspensions as well as patents on nanosuspension methods. PMID- 22077202 TI - Surfactant volume is an essential element in human toxicity in acute glyphosate herbicide intoxication. AB - BACKGROUND: Glyphosate, one of the most commonly used herbicides worldwide, has been considered as minimally toxic to humans. However, clinical toxicologists occasionally encounter cases of severe systemic toxicity. The purpose of this study was to determine the effect of glyphosate-surfactants ("glyphosate surfactant toxicity") in patients with acute glyphosate intoxication. METHODS: In all, 107 patients (69 men and 38 women, aged 52.3 +/- 15.5 years) with acute glyphosate intoxication were enrolled in this study. From their medical records, we identified the formulation of ingested glyphosate products and derived clinical parameters, which focused on clinical outcome, admission days, duration in the intensive care unit, development of respiratory failure, cardiovascular deterioration, renal failure, altered mental status, and convulsions. The effect of surfactants on clinical complications was also assessed. RESULTS: For surfactant ingestion volumes of 8 mL, the incidence of clinical complications was (in rank order) as follows: hypotension, 47.1%; mental deterioration, 38.6%; respiratory failure, 30.0%; acute kidney injury, 17.1%; and arrhythmia, 10.0%. These complications were influenced by the volume of surfactant and not the type of surfactant-ingredient in the herbicide product. Two patients died of refractory shock, metabolic acidosis, and respiratory failure. However, the final clinical outcomes of the surviving patients were benign, and cardiovascular, respiratory, kidney, and mental functions were fully restored to normal levels. CONCLUSIONS: Our results indicate that treatment of patients with acute glyphosate herbicide intoxication should take into account the volume and not the type of surfactants in herbicide formulations. PMID- 22077203 TI - Benzophenones and flavonoids from Hypericum maculatum and their antioxidant activities. AB - The occurrence of three known benzophenones, namely annulatophenonoside, acetylannulatophenonoside and annulatophenone as well as a flavonol O-glycoside guajaverin in the aerial parts of Hypericum maculatum Crantz was established. In addition, hyperoside, isoquercitrin and miquelianin were isolated from this plant, as well. Radical scavenging and antioxidant activities of the isolated compounds were examined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) free radicals, ferric reducing antioxidant power (FRAP) assay and inhibition of lipid peroxidation in linoleic acid system by the ferric thiocyanate method. Isoquercitrin demonstrates the highest DPPH radical scavenging (96.6 +/- 0.3%), FRAP (23.8 +/- 0.2 Trolox equivalent, TE mol-1) and antioxidant activity in linoleic acid system. Guajaverin and acetylannulatophenonoside show significantly strong ABTS radical scavenging activity (93.9 +/- 0.4% and 93.4 +/- 0.6%, respectively), which is comparable to that of ascorbic acid (96.2 +/- 0.4%). PMID- 22077204 TI - Emigration from the british isles to the u.s.a. In 1831. AB - Abstract This is a first attempt to use the original passenger manifests from immigrant ships entering U.S. ports to see what can be learned about emigration from the British Isles during the period of most rapid industrialization and urbanization between the Napoleonic Wars and the beginning of mass emigration in the late 1840s. Based on lists compiled during the years 1827 to 1831, the article demonstrates that these original lists contain more social and demographic information about migrants than was ever published by the U.S. government and also that the official statistics that were published were incomplete and exaggerated the fish share in the immigration through U.S ports. The English immigration is shown to have been predominantly a family movement in 1831, but most migrants chose to emigrate at favourable moments in the life cycle. Occupations and countries with low incomes were not well represented among English migrants through U.S. ports. As early as 1831, the majority of men among the English immigrants were industrial workers, though farmers (as distinct from farm labourers) were over-represented. PMID- 22077205 TI - Regional patterns of nuptiality in Europe, 1870-1960. AB - Abstract This paper is a study of changes in nuptiality by province in Europe between 1870 and 1960: nuptiality is measured by I(m) a summary measure of the proportions married among women of childbearing age. In each of the approximately 500 provinces of Europe the level of nuptiality increased between 1870 and 1960. In addition, in most countries the differences among provinces diminished over the period, so that the countries were more homogeneous with respect to provincial nuptiality in 1960 than they had been in 1870. Despite this tendency to convergence, traditional regional differences, linked to a common regional history, were often maintained, though within a narrower range. PMID- 22077206 TI - Estimating fertility trends from retrospective birth histories: Sensitivity to imputation of missing dates. AB - Abstract In the birth history section of the Core Questionnaire adopted by the countries participating in the World Fertility Survey a question on the date of birth of each child born to the respondent is asked. When the woman cannot provide a date, as is often the case in many developing countries, she is asked how many 'years ago' the birth occurred. If the default is used, the month and year of the birth is imputed by a computer program: However, there can be two plausible interpretations of the 'years ago' response: as completed years, the demographer's usual definition of age, or as rounded years. In this paper, data from the WFS Survey in Bangladesh are used to determine the sensitivity of recent fertility estimates to the interpretation of 'years ago'. It is found that if the woman meant rounded years, but completed years were assumed for imputation, the resulting evidence of a recent decline could be either exaggerated or false. The results have implications for other surveys in which the 'years ago' response is not an explicit option. PMID- 22077207 TI - A note on synthethic cohort estimates of average desired family size. AB - Abstract This note considers the problem of estimating average desired family size from parity-specific data on proportions wanting another child. Three procedures proposed in the literature are reviewed and shown to give seriously biased estimates, when women implement their fertility preferences. An alternative procedure is proposed which overcomes most of the deficiencies of previous methods. An example from Sri Lanka illustrates the fact that the differences among the methods may be quite substantial. PMID- 22077210 TI - Barotrauma-associated posterior tension pneumomediastinum, a rare cause of cardiac tamponade in a ventilated neonate: a case report and review of the literature. AB - Ventilation-associated neonatal barotrauma comprises a spectrum of conditions including pneumothorax, pulmonary interstitial emphysema, pneumopericardium and pneumomediastinum. Whilst pneumothorax is common, mediastinal and particularly posterior mediastinal air collections are rare. We report the case of a neonate, presenting with life threatening pericardial tamponade secondary to posterior tension pneumomediastinum. The infant was successfully resuscitated with an emergency left lateral thoracotomy and chest drain insertion. We believe this to be the first such case reported in the literature. We discuss aspects of pathophysiology, diagnosis and management relating to posterior pneumomediastinum. CONCLUSION: Posterior pneumomediastinum is rare, but can potentially cause fatal tamponade. Such cases must be managed in a tertiary centre where cardiology and surgical expertize are available. PMID- 22077212 TI - Triazole-modified triphenylene derivative: self-assembly and sensing applications. AB - Triphenylene-based discotic liquid crystal 3 bearing 1,2,3-triazole groups has been synthesized using "click" chemistry. Discotic mesogen 3 has good thermal stability, and incorporation of triazole groups results in stabilization of columnar mesophases down to room temperature and formation of organogels in cyclohexane and mixed solvents such as hexane and dichloromethane (4:1 v/v). Characterization of the organogel of 3 in cyclohexane revealed a porous network. However, presence of Cd(2+) ions in solution obstructed the self-assembly of this derivative due to preferred interactions between Cd(2+) ions and triphenylene units over pi-pi interactions among triphenylene groups. Further, strong emission of derivative 3 in its nonaggregated form makes it a promising fluorescence sensory material for nitroaromatic compounds. PMID- 22077211 TI - Outcomes on the pharmacopsychometric triangle in bupropion-SR vs. buspirone augmentation of citalopram in the STAR*D trial. AB - OBJECTIVE: To compare within the framework of a novel pharmacopsychometric triangle, augmentation treatment with bupropion vs. buspirone in the acute therapy of major depression in the STAR*D study. The triangle provides a composite view in three domains of antidepressive activity, side effects, and quality of life. METHOD: Within the pharmacopsychometric triangle, the short six item subscales of the Hamilton Depression Scale (HAM-D(17)) and of the Inventory of Depressive Symptomatology (IDS-C(30)), referred to as HAM-D(6) and IDS-C(6), were focussed on pure antidepressive effect. Side-effects (tolerable vs. intolerable) and quality of life were measured using patient-administered questionnaires. A modified intention to treat sample was used. RESULTS: Within the pharmacopsychometric triangle, bupropion-SR (sustained release) was superior to buspirone when augmented to the current citalopram treatment. Thus, in the domain of pure antidepressive effect, bupropion-SR was superior (P = 0.05) on the HAM-D(6), IDS-C(6), and IDS-C(30), but not on the HAM-D(17). In the domain of side effects, the total scores on the Patient Rated Inventory of Side Effects (PRISE) were reduced significantly more by bupropion-SR than by buspirone (P = 0.03). In the domain of quality of life, the total scores on the Quality of Life Enjoyment and Satisfaction Questionnaire (QLES-Q) showed a trend (P = 0.10) from baseline to endpoint of a superiority for bupropion-SR compared with buspirone. CONCLUSION: In all domains of the pharmacopsychometric triangle, bupropion-SR was superior to buspirone as augmentation therapy in depressed outpatients not responding to citalopram. PMID- 22077213 TI - Interaction mechanism of anabolic steroid hormones with structural components of erythrocyte membranes. AB - The interaction of testosterone, androsterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) with erythrocyte membranes was studied. It was shown that testosterone and androsterone have a high constant of binding to the membranes (K(b) ~ 10(6) M(-1)), whereas K(b)'s for DHEA and DHEAS are 2 orders of magnitude lower. Hydrogen bonds and hydrophobic interactions play an important role in binding of anabolic steroids. Hydrogen bonds form with CO and NH groups both of membrane proteins and phospholipids. This results in the formation of complex domains rising above the surface of membranes. Strengthening of hydrophobic interactions in the domains promotes the displacement of water dipoles to adjacent regions, thus loosening the phospholipid bilayer. Overall, microviscosity of erythrocyte membranes strongly increases, which decreases the plasticity of erythrocytes and hampers their motion in blood capillaries. This mechanism may underlie the development of diffusion myocardial hypoxia and hypoxic cardiac arrest. PMID- 22077192 TI - Rivaroxaban in patients with a recent acute coronary syndrome. AB - BACKGROUND: Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke. RESULTS: Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04). CONCLUSIONS: In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.). PMID- 22077214 TI - Biology without walls: the novel endocrinology of bone. AB - Classical studies of vertebrate physiology have usually been confined to a given organ or cell type. The use of mouse genetics has changed this approach and has rejuvenated the concept of a whole-body study of physiology. One physiological system that has been profoundly influenced by mouse genetics is skeletal physiology. Indeed, genetic approaches have identified several unexpected organs that affect bone physiology. These new links have begun to provide a plausible explanation for the evolutionary involvement of hormones such as leptin with bone physiology. These genetic approaches have also revealed bone as a true endocrine organ capable of regulating energy metabolism and reproduction. Collectively, the body of work discussed below illustrates a new and unconventional role for bone in mammalian physiology. PMID- 22077217 TI - The interplay between lipoprotein phenotypes, adiponectin, and alcohol consumption. AB - CONTEXT AND OBJECTIVE: Lipoproteins are involved in the pathophysiology of several metabolic diseases. Here we focus on the interplay between lipoprotein metabolism and adiponectin with the extension of alcohol intake. DESIGN AND SUBJECTS: Eighty-three low-to-moderate and 80 heavy alcohol drinkers were studied. Plasma adiponectin, other biochemical and extensive lipoprotein data were measured. Self-organizing maps were applied to characterize lipoprotein phenotypes and their interrelationships with biochemical measures and alcohol consumption. RESULTS: Alcohol consumption and plasma adiponectin had a strong positive association. Heavy alcohol consumption was associated with decreased low density lipoprotein cholesterol (LDL-C). Nevertheless, two distinct lipoprotein phenotypes were identified, one with elevated high-density lipoprotein cholesterol (HDL-C) and decreased very-low-density lipoprotein triglycerides (VLDL-TG) together with low prevalence of metabolic syndrome, and the other vice versa. The HDL particles were enlarged in both phenotypes related to the heavy drinkers. The low-to-moderate alcohol drinkers were characterized with high LDL-C and C-enriched LDL particles. CONCLUSIONS: The analyses per se illustrated the multi-faceted and non-linear nature of lipoprotein metabolism. The heavy alcohol drinkers were characterized either by an anti-atherogenic lipoprotein phenotype (with also the highest adiponectin concentrations) or by a phenotype with pro atherogenic and metabolic syndrome-like features. Clinically this underlines the need to distinguish the differing individual risk for lipid-related metabolic disturbances also in heavy alcohol drinkers. PMID- 22077215 TI - Stop the flow: a paradigm for cell signaling mediated by reactive oxygen species in the pulmonary endothelium. AB - The lung endothelium is exposed to mechanical stimuli through shear stress arising from blood flow and responds to altered shear by activation of NADPH (NOX2) to generate reactive oxygen species (ROS). This review describes the pathway for NOX2 activation and the downstream ROS-mediated signaling events on the basis of studies of isolated lungs and flow-adapted endothelial cells in vitro that are subjected to acute flow cessation (ischemia). Altered mechanical stress is detected by a cell-associated complex involving caveolae and other membrane proteins that results in endothelial cell membrane depolarization and then the activation of specific kinases that lead to the assembly of NOX2 components. ROS generated by this enzyme amplify the mechanosignal within the endothelial cell to regulate activation and/or synthesis of proteins that participate in cell growth, proliferation, differentiation, apoptosis, and vascular remodeling. These responses indicate an important role for NOX2-derived ROS associated with mechanotransduction in promoting vascular homeostasis. PMID- 22077218 TI - Alternative therapies for Helicobacter pylori: probiotics and phytomedicine. AB - Helicobacter pylori is a common human pathogen infecting about 30% of children and 60% of adults worldwide and is responsible for diseases such as gastritis, peptic ulcer and gastric cancer. Treatment against H. pylori is based on the use of antibiotics, but therapy failure can be higher than 20% and is essentially due to an increase in the prevalence of antibiotic-resistant bacteria, which has led to the search for alternative therapies. In this review, we discuss alternative therapies for H. pylori, mainly phytotherapy and probiotics. Probiotics are live organisms or produced substances that are orally administrated, usually in addition to conventional antibiotic therapy. They may modulate the human microbiota and promote health, prevent antibiotic side effects, stimulate the immune response and directly compete with pathogenic bacteria. Phytomedicine consists of the use of plant extracts as medicines or health-promoting agents, but in most cases the molecular mode of action of the active ingredients of these herbal extracts is unknown. Possible mechanisms include inhibition of H. pylori urease enzyme, disruption of bacterial cell membrane, and modulation of the host immune system. Other alternative therapies are also reviewed. PMID- 22077216 TI - Comparison of two yeast MnSODs: mitochondrial Saccharomyces cerevisiae versus cytosolic Candida albicans. AB - Human MnSOD is significantly more product-inhibited than bacterial MnSODs at high concentrations of superoxide (O(2)(-)). This behavior limits the amount of H(2)O(2) produced at high [O(2)(-)]; its desirability can be explained by the multiple roles of H(2)O(2) in mammalian cells, particularly its role in signaling. To investigate the mechanism of product inhibition in MnSOD, two yeast MnSODs, one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), were isolated and characterized. ScMnSOD and CaMnSODc are similar in catalytic kinetics, spectroscopy, and redox chemistry, and they both rest predominantly in the reduced state (unlike most other MnSODs). At high [O(2)(-)], the dismutation efficiencies of the yeast MnSODs surpass those of human and bacterial MnSODs, due to very low level of product inhibition. Optical and parallel-mode electron paramagnetic resonance (EPR) spectra suggest the presence of two Mn(3+) species in yeast Mn(3+)SODs, including the well-characterized 5-coordinate Mn(3+) species and a 6-coordinate L Mn(3+) species with hydroxide as the putative sixth ligand (L). The first and second coordination spheres of ScMnSOD are more similar to bacterial than to human MnSOD. Gln154, an H-bond donor to the Mn-coordinated solvent molecule, is slightly further away from Mn in yeast MnSODs, which may result in their unusual resting state. Mechanistically, the high efficiency of yeast MnSODs could be ascribed to putative translocation of an outer-sphere solvent molecule, which could destabilize the inhibited complex and enhance proton transfer from protein to peroxide. Our studies on yeast MnSODs indicate the unique nature of human MnSOD in that it predominantly undergoes the inhibited pathway at high [O(2)(-)]. PMID- 22077219 TI - Interferon gamma release assay in diagnosis of pediatric tuberculosis: a meta analysis. AB - Although interferon gamma release assays (IGRAs) have been widely used for the diagnosis of latent and active tuberculosis in adults, a relative lack of validation studies in children has led to caution in their clinical interpretation. This meta-analysis systematically evaluated two IGRAs (ELISA and ELISPOT) and the tuberculin skin test (TST). We searched databases (PubMed, MEDLINE, Ovid) between January 2000 and January 2011 using search terms of latent tuberculosis infection or tuberculosis and interferon gamma release assay, or T SPOT.TB test, or QuantiFERON-TB Gold, or ESAT-6, or CFP-10, and child, or childhood, or pediatrics. We also collected data by performing a manual search of references from relevant articles and communicating with selected authors. The meta-analysis was conducted with random effects models to account for heterogeneity between selected studies. The sensitivities of all three tests in active tuberculosis were similar. The pooled sensitivity was 70% for ELISA studies, 62% for ELISPOT studies and 71% for TST. Calculated sensitivities for IGRAs and the TST differ in culture-confirmed tuberculosis [ELISA (85%) vs. ELISPOT (76%) vs. TST (85%)] and clinical diagnosed cases [ELISA (64%) vs. ELISPOT (58%) vs. TST (66%)]. The pooled specificity was 100% for ELISA and 90% for ELISPOT, but was much lower for TST [56% in all included studies and 49% in children with bacillus Calmette-Guerin (BCG) vaccination]. The agreement between the TST and IGRAs in non-BCG-vaccinated children is higher than that in BCG vaccinated children. In the diagnosis of active tuberculosis in children, the TST and IGRAs have similar sensitivity. By contrast, the specificity of IGRAs is far greater than the TST, particularly in children with previous BCG vaccination. PMID- 22077220 TI - Proteomic analysis of Proteus mirabilis outer membrane proteins reveals differential expression in vivo vs. in vitro conditions. AB - Proteus mirabilis is an opportunistic pathogen that frequently causes complicated urinary tract infections. Among a wide spectrum of potential virulence factors, outer membrane proteins (OMPs) are critical for bacterial interactions and survival in different environments. In this work, we used a proteomic approach to assess P. mirabilis in vivo OMPs expression compared to in vitro, including iron replete and iron-restricted conditions. Three putative iron receptors, IreA, PMI0842, and PMI2596, were detected both in bacterium grown in vivo and in vitro under iron-restricted conditions. A prophage gene product, PMI1721, was detected only on in vivo growing bacterium, suggesting a potential role yet to be disclosed on the surface of P. mirabilis. Plasminogen, a host protein, was co purified with OMPs of in vivo grown bacteria, which is in accordance with previous observations and suggests that plasminogen bound to P. mirabilis surface may be associated to virulence as seen in other bacterial pathogens. Western blots using sera of experimentally challenged mice showed that iron-regulated proteins are expressed and highly immunogenic during infection. This work confirms observations made by others for P. mirabilis and reveals details not yet described, suggesting new aspects of the bacterium pathogenesis that remain unknown. PMID- 22077221 TI - Vgamma4+ T cells regulate host immune response to West Nile virus infection. AB - The Vgamma4(+) cells, a subpopulation of peripheral gammadelta T cells, are involved in West Nile virus (WNV) pathogenesis, but the underlying mechanism remains unclear. In this study, we found that WNV-infected Vgamma4(+) cell depleted mice had lower viremia and a reduced inflammatory response in the brain. The Vgamma4(+) cells produced IL-17 during WNV infection, but blocking IL-17 signaling did not affect host susceptibility to WNV encephalitis. We also noted that there was an enhanced magnitude of protective splenic Vgamma1(+) cell expansion in Vgamma4(+) cell-depleted mice compared to that in controls during WNV infection. In addition, Vgamma4(+) cells of WNV-infected mice had a higher potential for producing TGF-beta. The gammadelta T cells of WNV-infected Vgamma4(+) cell-depleted mice had a higher proliferation rate than those of WNV infected controls upon ex vivo stimulation with anti-CD3, and this difference was diminished in the presence of TGF-beta inhibitor. Finally, Vgamma4(+) cells of infected mice contributed directly and indirectly to the higher level of IL-10, which is known to play a negative role in immunity against WNV infection. In summary, Vgamma4(+) cells suppress Vgamma1(+) cell expansion via TGF-beta and increase IL-10 level during WNV infection, which together may lead to higher viremia and enhanced brain inflammation. PMID- 22077222 TI - Minimal concentration of human IgM and IgG antibodies necessary to protect mice from challenges with live O6 Escherichia coli. AB - This work evaluated the ability of human anti-lipopolysaccharide O6 IgM and IgG antibodies to protect mice challenged with Escherichia coli serotype O6 : K2ac. Purified IgM-effluent, purified IgG, pools of normal human serum (NHS), or control group were injected into mice 18 h before challenges with O6 E. coli. Interleukin 6 and tumor necrosis factor alpha were quantified in the sera of test and control groups. All mice receiving purified IgM-effluent (66.6 mg L(-1) of anti-lipopolysaccharide O6 IgM antibodies) and NHS survived. Purified IgG (1.1 mg L(-1) of anti-lipopolysaccharide O6 IgG antibodies) protected 87.5% of the animals. The control group showed no protective ability. The minimal concentration of anti-lipopolysaccharide O6 IgM antibodies, able to protect 50% of the animals was 33.3 mg L(-1) of purified IgM-effluent, whereas purified IgG was able to protect 50% of the animals with only 1.1 mg L(-1) of anti lipopolysaccharide O6 IgG antibodies. Serum from animals pretreated with purified IgM-effluent and purified IgG before challenges with lipopolysaccharide O6 did not have detectable pro-inflammatory cytokines. Hepatocytes of the control group were completely invaded by bacteria, whereas none was found in animals pretreated with purified IgM-effluent and purified IgG. Higher concentrations of anti lipopolysaccharide O6 IgM antibodies as compared to anti-lipopolysaccharide O6 IgG antibodies were needed to protect mice from challenges with E. coli O6 serotype. PMID- 22077223 TI - Bacillus cereus from blood cultures: virulence genes, antimicrobial susceptibility and risk factors for blood stream infection. AB - We characterized the profiles of virulence genes and antimicrobial susceptibility of Bacillus cereus isolates from blood cultures as well as the risk factors for blood stream infections (BSIs). The diversity of virulence gene patterns was found to be wide among 15 B. cereus isolates from BSIs and also among 11 isolates from contaminated blood cultures. The MicroScan broth microdilution method yielded results corresponding with those of the agar dilution (reference) method for levofloxacin, linezolid, and vancomycin, while the Etest results were consistent with the reference results for clindamycin, gentamicin, imipenem, levofloxacin, and linezolid. Compared with the reference values, however, some isolates showed marked differences of the minimum inhibitory concentrations (MICs) for ampicillin and clindamycin when determined using the MicroScan method, or the MICs for ampicillin, meropenem, and vancomycin when determined using the Etest method. Significantly more patients were treated with antimicrobials for more than 3 days during the 3-month period before isolation in the BSI group. Prior antimicrobial therapy may be a risk factor for BSIs due to B. cereus. PMID- 22077224 TI - Genotyping of Chlamydia trachomatis directly from urogenital and conjunctiva samples using an ompA gene pyrosequencing-based assay. AB - The aim of the present study was to develop and validate a multitarget pyrosequencing-based protocol for basic Chlamydia trachomatis genotyping directly from clinical samples and to characterize the distribution of genotypes among Slovenian sexually active population. The newly developed combination of assays that targets the variable domains VD-I and VD-IV of the C. trachomatis ompA gene, was optimized and validated with 11 reference C. trachomatis strains and by comparison to complete ompA conventional sequencing. In addition, 183 clinical specimens which were previously diagnosed as C. trachomatis positive were evaluated by pyrosequencing. The pyrosequencing products showed a 100% match to corresponding sections of the respective conventional ompA sequences. Based on our results the most frequent genotype in urogenital samples was E (51.1%) followed by F (21.4%), G and K (6.9%), D (6.1%), H (3.8%), J (2.3%) and Ia and Ja (0.8%). In conjunctiva samples the genotype distribution was E (63.3%), D and F (13.3%), K (6.7%) and G (3.3%). Pyrosequencing thus proved itself to be a rapid method for C. trachomatis typing, which is important for better understanding the pathogenesis and epidemiology of this pathogen. PMID- 22077225 TI - Effects of the microbial secondary metabolites pyrrolnitrin, phenazine and patulin on INS-1 rat pancreatic beta-cells. AB - The effects on pancreatic beta-cell viability and function of three microbial secondary metabolites pyrrolnitrin, phenazine and patulin were investigated, using the rat clonal pancreatic beta-cell line, INS-1. Cells were exposed to 10 fold serial dilutions (range 0-10 MUg mL(-1)) of the purified compounds for 2, 24 and 72 h. After 2 h exposure, only patulin (10 MUg mL(-1)) was cytotoxic. All compounds showed significant cytotoxicity after 24 h. None of the compounds altered insulin secretion with 2 and 20 mM glucose after 2 h. However, after 24 h treatment, phenazine and pyrrolnitrin (10 and 100 ng mL(-1)) potentiated insulin production and glucose-stimulated insulin secretion, whereas patulin had no effect. Exposure (24 h) to either phenazine (100 ng mL(-1)) or pyrrolnitrin (10 ng mL(-1)) caused similar increases in the Ca(2+) content of INS-1 cells. The outward membrane current was inhibited after 24 h exposure to either phenazine (100 ng mL(-1)) or pyrrolnitrin (10 or 100 ng mL(-1)). This study presents novel data suggesting that high concentrations of pyrrolnitrin and phenazine are cytotoxic to pancreatic beta-cells and thus possibly diabetogenic, whereas at lower concentrations these agents are nontoxic and may be insulinotropic. The possible role of such agents in the development of cystic fibrosis-related diabetes is discussed. PMID- 22077226 TI - Astragalus polysaccharides enhance the humoral and cellular immune responses of hepatitis B surface antigen vaccination through inhibiting the expression of transforming growth factor beta and the frequency of regulatory T cells. AB - Astragalus polysaccharides (APS), extracted from the root of Astragalus membranaceus, a traditional Chinese medicinal herb, have extensive pharmacological and strong immunomodulatory effects. In this study, the potential adjuvant effect of APS on humoral and cellular immune responses to hepatitis B subunit vaccine was investigated. Coadministration of APS with recombinant hepatitis B surface antigen significantly increased antigen-specific antibody production, T-cell proliferation and CTL (cytotoxic T lymphocyte) activity. Production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and IL-4 in CD4(+) T cells and of IFN-gamma in CD8(+) T cells were dramatically increased. Furthermore, expression of the genes PFP, GraB, Fas L and Fas were up-regulated; interestingly, expression of transforming growth factor beta (TGF-beta) and the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells) were down regulated. Expression of Toll-like receptor 4 (TLR4) was significantly increased by administration of APS. Together, these results suggest that APS is a potent adjuvant for the hepatitis B subunit vaccine and can enhance both humoral and cellular immune responses via activating the TLR4 signaling pathway and inhibit the expression of TGF-beta and frequency of Treg cells. PMID- 22077227 TI - Vancomycin promotes the bacterial autolysis, release of extracellular DNA, and biofilm formation in vancomycin-non-susceptible Staphylococcus aureus. AB - Staphylococcus aureus, an important human pathogen, is particularly adept at producing biofilms on implanted medical devices. Although antibiotic treatment of nonsusceptible bacteria will not kill these strains, the consequences should be studied. The present study focuses on investigating the effect of vancomycin on biofilm formation by vancomycin-non-susceptible S. aureus. Biofilm adherence assays and scanning electron microscopy demonstrated that biofilm formation was significantly enhanced following vancomycin treatment. Bacterial autolysis of some subpopulations was observed and was confirmed by the live/dead staining and confocal laser scanning microscopy. A significant increase in polysaccharide intercellular adhesin (PIA) production was observed by measuring icaA transcript levels and in a semi-quantitative PIA assay in one resistant strain. We show that the release of extracellular DNA (eDNA) via cidA-mediated autolysis is a major contributor to vancomycin-enhanced biofilm formation. The addition of xenogeneic DNA could also significantly enhance biofilm formation by a PIA-overproducing S. aureus strain. The magnitude of the development of the biofilm depends on a balance between the amounts of eDNA and PIA. In conclusion, sublethal doses of cell wall-active antibiotics like vancomycin induce biofilm formation through an autolysis-dependent mechanism in vancomycin-non-susceptible S. aureus. PMID- 22077228 TI - Emerging dynamics of human campylobacteriosis in Southern Ireland. AB - Infections with Campylobacter spp. pose a significant health burden worldwide. The significance of Campylobacter jejuni/Campylobacter coli infection is well appreciated but the contribution of non-C. jejuni/C. coli spp. to human gastroenteritis is largely unknown. In this study, we employed a two-tiered molecular study on 7194 patient faecal samples received by the Microbiology Department in Cork University Hospital during 2009. The first step, using EntericBio((r)) (Serosep), a multiplex PCR system, detected Campylobacter to the genus level. The second step, utilizing Campylobacter species-specific PCR identified to the species level. A total of 340 samples were confirmed as Campylobacter genus positive, 329 of which were identified to species level with 33 samples containing mixed Campylobacter infections. Campylobacter jejuni, present in 72.4% of samples, was the most common species detected, however, 27.4% of patient samples contained non-C. jejuni/C. coli spp.; Campylobacter fetus (2.4%), Campylobacter upsaliensis (1.2%), Campylobacter hyointestinalis (1.5%), Campylobacter lari (0.6%) and an emerging species, Campylobacter ureolyticus (24.4%). We report a prominent seasonal distribution for campylobacteriosis (Spring), with C. ureolyticus (March) preceeding slightly C. jejuni/C. coli (April/May). PMID- 22077229 TI - Extensive viral mimicry of 22 AIDS-related autoantigens by HIV-1 proteins and pathway analysis of 561 viral/human homologues suggest an initial treatable autoimmune component of AIDS. AB - HIV-1 viral proteins, particularly the env protein, are homologous to 22 AIDS autoantigens, suggesting their creation by antiviral antibodies subsequently targeting human homologues. They include antibodies to T-cell receptors, CD4 and CD95, complement components, IgG, TNF and other immune-related proteins. Autoantibodies may compromise the immune system via knockdown of these key proteins, and autoimmune attack on the immune system itself, as supported by immune activation in early stages of infection and during the transition to AIDS. Over 500 human proteins contain pentapeptides or longer consensi, identical to viral peptides. Such homology explains the extensive viral/human interactome, likely related to the ability of viral homologues to compete with human counterparts as binding partners. Pathway analysis of these homologous proteins revealed their involvement in immune-related networks (e.g. natural killer cell toxicity/toll, T-cell/B-cell receptor signalling/antigen processing) and viral and bacterial entry and defence pathways (phagosome/lysosome pathways, DNA sensing/NOD/RIG-1 pathways) relevant to AIDS pathogenesis. At its inception, AIDS may have an autoimmune component selectively targeting the immune system. Immunosuppressive therapy or antibody removal, which has already achieved some success, might be therapeutically beneficial, particularly if targeted at removal of the culpable antibodies, via affinity dialysis. PMID- 22077230 TI - Staphylococcus epidermidis polysaccharide intercellular adhesin activates complement. AB - Staphylococcus epidermidis is a frequent cause of nosocomial infections. The central virulence factor of S. epidermidis is biofilm formation. Polysaccharide intercellular adhesin (PIA) constitutes the major biofilm matrix-component. PIA and biofilm have been implicated in S. epidermidis evasion of host immune defence. We examined the effects of S. epidermidis PIA on the inflammatory response with focus on complement activation. We used a human whole-blood ex vivo model of infection and compared the effects of a PIA-positive S. epidermidis strain (SE1457) and its PIA-negative isogenic mutant (M10). The independent effect of purified PIA on complement activation was investigated. In glucose-rich media, the mutant formed a proteinacious DNA-rich biofilm, whereas SE1457 formed a thick PIA-biofilm. In biofilm growth, SE1457 induced a stronger activation of the complement system compared with M10. We verified that purified PIA was independently responsible for a strong activation of the complement system. In contrast, M10 induced higher granulocyte activation by expression of CD11b and higher secretion of cytokines. We conclude that PIA has potent pro-inflammatory properties by activating the complement system. However, in a complex balance of the immune response, the decreased activation of granulocytes and cytokines by a PIA biofilm may limit host eradication of S. epidermidis. PMID- 22077231 TI - Immunolocalization of IFN-gamma in the lesions of resistant and susceptible mice to Paracoccidioides brasiliensis infection. AB - The important role of interferon-gamma (IFN-gamma) in protective immunity in mycosis is well established, except for its participation in fungal granulomas. Herein, we employ immunohistochemical reactions to describe the in situ localization of IFN-gamma in granulomas of susceptible (B10.A) and resistant (A/J) mice to infection with Paracoccidioides brasiliensis (Pb). After infection with the highly virulent Pb18, IFN-gamma-positive lymphomononuclear cells were localized mainly at the periphery of granulomas in both mouse strains. The numbers of positive cells found in compact granulomas of A/J mice increased significantly from 15 to 120 days postinfection. At this time, significantly more positive cells were detected in the compact granulomas of resistant mice than in the loose, multifocal lesions of the susceptible ones. In infection with the slightly virulent Pb265, the same pattern of IFN-gamma localization was found as in Pb18 infection, but there was decreased staining at 120 days due to the presence of only residual lesions in both mouse strains. The marked IFN-gamma staining observed in the granulomas of resistant mice at the later stage of Pb infection confirms its importance in fungal dissemination control, and suggests a contribution to the development of paracoccidioidal granuloma. PMID- 22077232 TI - Immune responses of chickens inoculated with a recombinant fowlpox vaccine coexpressing glycoprotein B of infectious laryngotracheitis virus and chicken IL 18. AB - Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that causes severe and economically significant respiratory disease in poultry worldwide. Herein, the immunogenicity of two recombinant fowlpox viruses (rFPV-gB and rFPV gB/IL18) containing ILTV glycoprotein B (gB) and chicken interleukin-18 (IL-18) were investigated in a challenge model. One-day-old specific-pathogen-free chickens were vaccinated by wing-web puncture with the two rFPVs and challenged with the virulent ILTV CG strain. There were differences in antibody levels elicited by either rFPV-gB/IL18 or rFPV-gB as determined using ELISA. The ratios of CD4(+) to CD8(+) in chickens immunized with rFPV-gB/IL18 were higher (P < 0.05) than in those immunized with rFPV-gB, and the level of proliferative response of the T cells in the rFPV-gB/IL18-vaccinated group was higher (P < 0.05) than that in the rFPV-gB group. All chickens immunized with rFPV-gB/IL18 were protected (10/10), whereas only eight of 10 of the chickens immunized with the rFPV-gB were protected. The results showed that the protective efficacy of the rFPV-gB vaccine could be enhanced by simultaneous expression of chicken IL 18. PMID- 22077234 TI - European veterinary dissertations. PMID- 22077233 TI - Multiple forms of DNA damage caused by UVA photoactivation of DNA 6-thioguanine. AB - Thiopurines are prescribed frequently as medication for cancer and for inflammatory disorders. One of them, azathioprine, has been the immunosuppressant of choice for organ transplant recipients for many years. Thiopurine use is associated with elevated sun sensitivity and skin cancer risk. Skin sensitization is selective for UVA. 6-TG integrates into DNA and unlike the canonical DNA bases, it is a strong UVA chromophore with an absorbance maximum at 342 nm. DNA 6 TG is a photosensitizer and a source of reactive oxygen species. Reactive oxygen that is generated from the photochemical activation of DNA 6-TG causes extensive damage to DNA and proteins. This damage is mutagenic and extremely toxic to cultured human cells. Here we describe some of the lesions that are known to be generated from UVA irradiation of DNA 6-TG. We discuss how this photochemical damage might contribute to the toxic effect of thiopurine/UVA treatment on cultured cells and to the high risk of skin cancer in thiopurine-treated patients. PMID- 22077235 TI - Case of rippled-pattern sebaceoma with clinically yellowish surface and histopathological paucity of lipid-containing neoplastic cells. PMID- 22077237 TI - Is contrast-enhanced 3D spoiled gradient echo MRI a superior way to image pachymeningeal enhancement in intracranial hypotension? PMID- 22077238 TI - Aclarubicin enhances tumor necrosis factor-related apoptosis-inducing ligand induced apoptosis through death receptor 5 upregulation. AB - Anthracycline drugs are potent anti-tumor agents. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand with promising anti-cancer effects. However, some tumor types develop resistance to TRAIL. We examined the effect of aclarubicin (ACR), an anthracycline, in combination with TRAIL. The combination of TRAIL and ACR synergistically induced apoptosis in human acute lymphoblastic leukemia Jurkat cells and human lung cancer A549 cells. In contrast, another anthracycline, doxorubicin (DOX), only slightly sensitized Jurkat cells and A549 cells to TRAIL-induced apoptosis, with weaker enhancement of death receptor 5 (DR5) expression than ACR. The RNase protection assay, real time RT-PCR and western blot demonstrated that ACR upregulated the expression of a TRAIL receptor, DR5. Caspase inhibitors and dominant negative DR5 efficiently reduced the apoptotic response to the treatment with ACR and TRAIL, indicating that the combined effect depends on caspase activities and the interaction between TRAIL and its receptor. ACR but not DOX increased the activity of the DR5 gene promoter in Jurkat cells carrying a mutation in the p53 gene, suggesting that ACR upregulates DR5 expression through p53-independent transcription. These results suggest the combination of TRAIL and ACR to be a promising treatment for malignant tumors. PMID- 22077239 TI - Dihydroxylation-based approach for the asymmetric syntheses of hydroxy-gamma butyrolactones. AB - A method of preparing enantiopure hydroxy-gamma-butyrolactones containing multiple contiguous stereocenters in high yield with good diastereoselectivity has been developed. Osmium tetroxide mediated dihydroxylation of a range of beta alkenyl-beta-hydroxy-N-acyloxazolidin-2-ones results in formation of triols that undergo spontaneous intramolecular 5-exo-trig cyclization reactions to provide hydroxy-gamma-butyrolactones. The stereochemistry of these hydroxy-gamma butyrolactones has been established using NOE spectroscopy, which revealed that 1 substituted, 1,1-disubstituted, (E)-1,2-disubstituted, (Z)-1,2-disubstituted, and 1,1,2-trisubstituted alkenes undergo dihydroxylation with anti diastereoselectivity, while 1,2,2-trisubstituted systems afford syn diastereoisomers. The synthetic utility of this methodology has been demonstrated for the asymmetric synthesis of the natural product 2-deoxy-D-ribonolactone. PMID- 22077240 TI - Embryonic exposure to dimethoate and/or deltamethrin impairs sexual development and programs reproductive success in adult male offspring mice. AB - Pesticides can be toxic to desirable plants and animals, including humans. The aim of this study was to investigate the reproductive effects of low doses of pesticides on male offspring of exposed pregnant mice. Three groups of five female mice were treated daily by oral gavage with dimethoate (5 mg kg(-1) per day), deltamethrin (5 mg kg(-1) per day) and their mixture at 5 mg kg(-1) per day from day 3 to day 21 of pregnancy. Fertility, sexual behaviour and a number of reproductive endpoints, such as organ weights, sperm evaluations and testicular histology, were examined on four adult male offspring of exposed pregnant mice. When compared with control, a dose of deltamethrin 5 mg kg j(-1) causes a decrease in the absolute and relative weight of the testes of exposed mice and it affects their fertility by reducing the density, mobility and vitality of sperm and increasing the number of abnormal forms of these cells (P <= 0.01). The same results were obtained in mice exposed to a dose of 5 mg kg j(-1) combination of dimethoate and deltamethrin. This study demonstrated that deltamethrin and combination of dimethoate and deltamethrin caused a decrease in the absolute and relative weight of the testes, which affected the sperm parameters of male offspring of exposed mice to a low dose of these pesticides during pregnancy. PMID- 22077241 TI - Hollow fiber membrane decorated with Ag/MWNTs: toward effective water disinfection and biofouling control. AB - The currently applied disinfection methods during water treatment provide effective solutions to kill pathogens, but also generate harmful byproducts, which are required to be treated with additional efforts. In this work, an alternative and safer water disinfection system consisting of silver nanoparticle/multiwalled carbon nanotubes (Ag/MWNTs) coated on a polyacrylonitrile (PAN) hollow fiber membrane, Ag/MWNTs/PAN, has been developed. Silver nanoparticles of controlled sizes were coated on polyethylene glycol grafted MWNTs. Ag/MWNTs were then covalently coated on the external surface of a chemically modified PAN hollow fiber membrane to act as a disinfection barrier. A continuous filtration test using E. coli containing feedwater was conducted for the pristine PAN and Ag/MWNTs/PAN composite membranes. The Ag/MWNT coating significantly enhanced the antimicrobial activities and antifouling properties of the membrane against E. coli. Under the continuous filtration mode using E. coli feedwater, the relative flux drop over Ag/MWNTs/PAN was 6%, which was significantly lower than that over the pristine PAN (55%) at 20 h of filtration. The presence of the Ag/MWNT disinfection layer effectively inhibited the growth of bacteria in the filtration module and prevented the formation of biofilm on the surface of the membrane. Such distinctive antimicrobial properties of the composite membrane is attributed to the proper dispersion of silver nanoparticles on the external surface of the membrane, leading to direct contact with bacterium cells. PMID- 22077242 TI - Dialkyl phosphates as biomarkers of organophosphates: the current divide between epidemiology and clinical toxicology. AB - CONTEXT: Organophosphate insecticides are widely utilized throughout the world. The cholinergic toxidrome, resulting from cholinesterase inhibition, is the clinically relevant endpoint in organophosphate poisoning. In recent years, urinary dialkyl phosphates (DAPs) have emerged as a common method of assessing exposure to organophosphates in epidemiological investigations. Using dialkyl phosphates as biomarkers of exposure to organophosphates, several recent epidemiological studies have reported associations with adverse health outcomes. The purpose of this article is to review the application and limitations of urinary DAPs as biomarkers of exposure to organophosphate insecticides. METHODS: A literature search was conducted of the PubMed database, using keywords "dialkylphosphate" and "dialkyl phosphate." The scientific literature was reviewed to identify sources of dialkyl phosphate metabolites from in vivo metabolism of organophosphates, and as environmental degradation products. Epidemiological investigations were reviewed to summarize the use of use of DAPs as biomarkers in cross-sectional studies, occupational exposures, acute poisonings, and in health outcome studies. Emphasis was placed on the assessment of DAPs in the context of existing biomarker frameworks, as defined by the National Research Council. Studies were assessed for concurrent use of cholinesterase activity as a biomarker of effect, and whether a dose-response relationship could be determined between DAPs and cholinesterase depression or cholinergic effects. RESULTS: Over 184 publications were identified, describing dialkyl phosphates and their use as biomarkers of exposure. The in vivo metabolism of organophosphates yields different DAPs, depending upon whether they undergo bioactivation or detoxification. The detection of urinary DAPs does not provide specificity with respect to the organophosphate from which they were derived, or their toxicological potency. Several recent studies documented the common presence of DAPs in residential environments and foods. Experimental studies support that DAPs have significant oral bioavailability, and undergo little to no metabolism prior to urinary excretion. Cross-sectional studies in multiple countries confirm that urinary DAPs are commonly detectable in the general population. No occupational studies were identified supporting a dose response relationship between DAPs and significant cholinesterase inhibition. No occupational studies were identified supporting evidence of a threshold level of DAPs excretion at which clinical cholinergic signs or symptoms have been observed. Recent prospective epidemiological studies using DAPs as biomarkers have not concurrently assessed effects on cholinesterase activity, or conducted analyses that distinguish different DAPs that reflect bioactivation versus detoxification pathways. DISCUSSION: There are numerous limitations to the use of DAPs as biomarkers of exposure. These include a lack of specificity with respect to the organophosphate from which they were derived, and a growing body of evidence that toxicologically irrelevant DAPs are commonly encountered in food and the environment. Substantial intra- and inter-day variability has been reported for dialkyl phosphate excretion in humans, which is problematic for studies that rely on single measurements to assess exposure. The toxicological distinction between different DAPs reflecting biomarkers of activation and detoxification processes has not been considered in some prospective epidemiological studies. A relationship between DAPs as biomarkers of exposure and the critical biomarker of effect, cholinesterase activity, has not been established. CONCLUSIONS: The science of exposure assessment using DAPs as biomarkers is not advancing, and this complicates the interpretation of epidemiological studies. At the current time, DAPs have very limited utility in clinical toxicology or in the risk assessment process for organophosphates. Until these limitations are addressed, the appropriate role of DAPs in the assessment of human health risks from organophosphates is unclear. PMID- 22077243 TI - Use of the molecular adsorbent recirculating system (MARSTM) for the management of acute poisoning with or without liver failure. AB - INTRODUCTION: There is an increasing interest in recent developments in bioartificial and non-bioartificial devices, so called extracorporeal liver assist devices, which are now used widely not only to increase drug elimination, but also to enhance the removal of endogenous substances in acute liver failure. Most of the non-bioartificial techniques are based on the principle of albumin dialysis. The objective is to remove albumin-bound substances that could play a role in the pathophysiology of acute liver failure by dialysing blood against an albumin-containing solution across a high flux permeable membrane. The most widely used device is the Molecular Adsorbent Recirculating System (MARSTM). METHODS: The relevant English and French literature was identified through Medline using the terms, 'molecular adsorbent recirculating system', 'MARS', 'acute liver failure', 'acute poisoning', 'intoxication'. This search identified 139 papers of which 48 reported on a toxic cause for the use of MARSTM. Of these 48 papers, 39 specified the substance (eighteen different substances were identified); two papers reported on the same group of patients. BIOARTIFICIAL AND NON-BIOARTIFICIAL SYSTEMS: Bioartificial systems based on porcine hepatocytes incorporated in the extracorporeal circuit are no longer in use due to the possibility of porcine retroviral transmission to humans. Historically, experience with such devices was limited to a few cases of paracetamol poisoning. In contrast, an abundant literature exists for the non-bioartificial systems based on albumin dialysis. The MARSTM has been used more widely than other techniques, such as the one using fractionated plasma separation and adsorption (PrometheusTM). All the extracorporeal liver assist devices are able to some extent to remove biological substances (ammonia, urea, creatinine, bilirubin, bile acids, amino acids, cytokines, vasoactive agents) but the real impact on the patient's clinical course has still to be determined. Improvement in cardiovascular or neurological dysfunction has been shown both in acute liver failure and acute-on-chronic liver failure but no impact on mortality has been reported. ACUTE POISONING WITH LIVER FAILURE: Randomized controlled trials are very limited in number and patients poisoned by paracetamol or Amanita phalloides are usually included for outcome analysis in larger groups of acute liver failure patients. Initial results look promising but should be confirmed. Beyond its effect in liver failure, MARSTM could also enhance the elimination of the drug or toxin responsible for the failure, as is described with paracetamol. ACUTE POISONING WITHOUT LIVER FAILURE: Extracorporeal liver assist devices have also been used to promote elimination of drugs that are highly protein bound. Data in various case reports confirm a high elimination of phenytoin, theophylline and diltiazem. However, definite conclusions on the toxicokinetic or clinical efficacy cannot be drawn. CONCLUSIONS: Despite the lack of large multicentre randomized trials on the use of MARSTM in patients with acute liver failure, the literature shows clinical and biological benefit from this technique. In drug or toxin-induced acute liver failure, such as paracetamol or mushroom poisoning, MARSTM has been used extensively, confirming in a non-randomized fashion, the positive effect observed in the larger population of acute liver failure patients. Furthermore, as MARSTM has been shown in experimental studies to remove protein-bound substances, it is potentially a promising treatment for patients with acute poisoning from drugs that have high protein-binding capacity and are metabolized by the liver, especially, if they develop liver failure concomitantly. PMID- 22077244 TI - Implications of the new EU legislation on chemicals for Poisons Centres. PMID- 22077245 TI - Interactive voice response systems for medication identification requests: poison or cure? AB - Interactive voice response systems (IVR) have traditionally been used by banking and credit card industries to rapidly process information requests for their customers. Today IVR technology is being used in clinical medicine to randomize patients in clinical studies, to collect patient data, and to follow-up on recently discharged patients. Use of IVR systems by poison centers is relatively new. This commentary explores the advantages and disadvantages of applying IVR technology to the medication identification requests in poison centers. PMID- 22077246 TI - Assessment of the severity of organophosphate (fenitrothion) poisoning based on its serum concentration and clinical parameters. AB - BACKGROUND: Fenitrothion (MEP) is the most frequent cause of organophosphate pesticides (OP) poisoning in Japan, but clinical parameters to predict its severity remain uncertain. METHOD: We evaluated 26 cases (12 males and 14 females) of MEP poisoning brought to our critical care center. Regarding acute lung injury (ALI) as a hallmark complication leading to poor recovery, we divided patients into two groups: cases without ALI (Grp1, n = 14), and cases who developed ALI (Grp2, n = 12) at various points after the poisoning. Serial changes in clinical parameters and laboratory test results were compared between them. RESULTS: The median MEP concentrations on arrival (min~max) for Grp1 and Grp2 were 2.3 (0.5-5.1) and 4.6 (1.1-14.0) MUg/ml, respectively. Serum pseudo cholinesterase (PChE) levels on arrival were 21(< 10-59) U/L in Grp1 and < 10 in Grp2. Based on individual patient kinetics, we estimated MEP concentration at 2 and 24 hours after ingestion, and determined cutoff values for differentiating the two groups for each time point as 4.0 MUg/ml and 0.5 MUg/ml, respectively. By logistic regression analysis, two groups were distinguished with accuracy of 92.3% based on their time of arrival after ingestion and initial MEP concentration. Clinical parameters associated with ALI were days with miosis, days with PChE below 100 U/L, and days requiring administration of atropine. CONCLUSION: The severity of MEP poisoning is closely associated with both time to presentation after ingestion and initial MEP concentration. Serial monitoring of MEP concentrations in the first 24 hours is also useful in predicting the clinical course. PMID- 22077247 TI - Prediction of prognosis in acute paraquat poisoning using severity scoring system in emergency department. AB - OBJECTIVE: The aim of this study was to validate and compare the performance of serum paraquat level, severity index of paraquat poisoning (SIPP), Acute Physiology And Chronic Health Evaluation II (APACHE II), modified Simplified Acute Physiology Score II (MSAPS II), and modified Expanded Simplified Acute Physiology Score II (MSAPS IIe) calculated immediately after arrival on emergency department (ED) for assessing the mortality of acute paraquat poisoning. METHODS: A retrospective study design was employed with the main outcome measure being mortality from year 2001 to 2010. MSAPS II and MSAPS IIe were employed in that assessment of the 24-hour urine output were not included. The performance of APACHE II, MSAPS II, MSAPS IIe, serum paraquat level and SIPP for prediction of mortality in acute paraquat poisoning were compared. RESULTS: A total of 102 patients were enrolled in the study. The area under the ROC curve for APACHE II (0.800) was statistically lower than those for MSAPS II, MSAPS IIe, SIPP and serum paraquat (0.879, 0.893, 0.924,and 0.951, respectively). The Hosmer-Lemeshow goodness-of-fit test C statistic revealed that APACHE II, MSAPS II, MSAPS IIe and serum paraquat level showed good calibrations (chi-square 8.477 and p = 0.388, chi-square 4.614 and p = 0.798, chi-squared 5.301 and p = 0.725, chi-squared 1.009 and p = 0.985 respectively), but poor calibration for SIPP (chi-square 21.293 and p = 0.006). CONCLUSION: Serum paraquat level is still the most reliable prognosis factor in acute paraquat poisoning. But MSAPS II or MSAPS IIe calculated immediately after arrival on ED may be helpful to predict mortality in acute paraquat poisoning especially when hospital has no facility to measure serum paraquat level. PMID- 22077236 TI - Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. AB - BACKGROUND: An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population. METHODS: In the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m(2) of body-surface area at two consecutive study visits. RESULTS: Over a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m(2) during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m(2) (P<0.001 for both comparisons). The beneficial effect of intensive therapy on the risk of an impaired GFR was fully attenuated after adjustment for glycated hemoglobin levels or albumin excretion rates. CONCLUSIONS: The long-term risk of an impaired GFR was significantly lower among persons treated early in the course of type 1 diabetes with intensive diabetes therapy than among those treated with conventional diabetes therapy. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360815 and NCT00360893.). PMID- 22077249 TI - A regional poison information center IVR medication identification system: does it accomplish its goal? AB - BACKGROUND: The 2009 AAPCC NPDS report identified 1,057,632 medication identification requests to poison information centers. This represents 24.7% of all calls to US poison information centers. To reduce the impact of medication identification requests on a poison information center, a regional poison information center developed and implemented an automated medication identification system that utilized an interactive voice response (IVR) system. The objective of this project was to describe how the IVR affected the regional poison information center medication identification request call volume and workload of the staff. METHODS: All documented medication identification request inquiries from January 1, 2007 through June 30, 2011 were extracted from the RPIC Visual Dotlab electronic medical record system. Descriptive statistics, presented as means, were used to characterize the monthly call volume inquiries. RESULTS: Over the 18 months (January, 2007 to June, 2008) preceding the implementation of the IVR medication identification request system, a mean of 4,389.6 medication identification requests per month required manual electronic documentation by SPI. In the immediate 12 months (August, 2008 to July, 2009) following the IVR medication identification request system implementation, a mean of 2132.6 inquiries per month (54% reduction) were managed by the IVR. During the 12 month period of July, 2010 through June, 2011, the combined monthly mean of medication identification requests documented by SPI and the IVR decreased to a total of 686.7 compared to the mean pre-implementation monthly total of 4,389.6. CONCLUSIONS: The IVR medication identification request system was successful in reducing the number of medication identification requests that required manual electronic documentation by SPI and freed up a substantial amount of time for SPI to perform other critical patient care-related responsibilities. The enhanced technology that was implemented to improve efficiency came with the unintended consequence of discouraging the public from using the RPIC medication identification service as extensively. PMID- 22077248 TI - Clinical and analytical features of severe suicidal quetiapine overdoses--a retrospective cohort study. AB - CONTEXT: Detailed data on severe overdoses with quetiapine are relatively sparsely reported in the literature. OBJECTIVE: To describe a cohort of 20 acute quetiapine overdoses and provide additional data on the pharmacokinetics and clinical features of intoxication with this drug. MATERIAL AND METHODS: A retrospective study was conducted on patients with quetiapine poisoning admitted to our institution. We included moderate to severe overdoses between 2005-2011 who required admission to ICU. RESULTS: Predominantly female patients (n = 17) ingested a median dose of 9.8 g quetiapine. Poison Severity Score was moderate in 9 patients, severe in 10 patients and in one case fatal. Quetiapine was analytically confirmed in all cases. Clinical manifestations included drowsiness or coma (all patients), tachycardia (12 patients) and hypotension (10 patients). Seizures and arrhythmia occurred in 4 patients, each. Intubation and mechanical ventilation was required in 14 patients due to seizures, respiratory depression or loss of airway protection and 15 patients developed pneumonia. Hypokalaemia and hyperglycaemia were present at admission in 10 and 5 patients, respectively. Despite frequent prolongation of the QT(c) in 13 patients, QT interval was normal in most cases and QRS-interval was prolonged in only one patient. Presumably anticholinergic delirium was recognised in 8 patients and 6 patients received physostigmine with good clinical response. In 13 cases quetiapine was analysed quantitatively in serum with a relevantly prolonged half-life (16 +/- 12 h) and a median peak serum concentration of 3074 ng/mL. In 4 of these 13 patients we observed an increase of quetiapine serum concentration in the further course. CONCLUSION: In this study, quetiapine overdoses were associated with significant toxicity and a fairly high number of complications. A careful and often prolonged clinical observation in the more severe cases of overdose seems mandatory. PMID- 22077250 TI - Cannabis body packing: two case reports. AB - INTRODUCTION: Body packing is a well-known means of narcotic carriage across international borders. The most common drugs carried are cocaine and heroin. CASE DESCRIPTIONS: We describe 2 cases of cannabis body packing which occurred the same year in the South of France, one with complications: a 45-year-old male went to emergency for abdominal pain. A plain abdominal x-ray revealed multiple foreign bodies in the gastrointestinal tract. It was confirmed by abdominal CT. The laparatomy confirmed peritonitis secondary to colonic perforation, and 34 filled condoms packages were extracted. After calling poison centre, toxicological analysis was performed on one package. The resin wrapped in cellophane contained 15% tetrahydrocannabinol (THC). The patient was discharged on day 12. DISCUSSION/CONCLUSION: Cannabis body packing is rarely reported, and the only known complications have a mechanic etiology. Plain abdominal x-ray is the best method for detection and it can be confirmed by abdominal CT and toxicological analysis. Cannabis is the most important illicit drug used in the word. Also cannabis body packing is probably underestimated. Health care practitioners should be aware of the possibility of body packing when someone coming back from abroad complains of abdominal pain. PMID- 22077251 TI - Severe acute cardiomyopathy associated with venlafaxine overdose and possible role of CYP2D6 and CYP2C19 polymorphisms. AB - INTRODUCTION: Venlafaxine (VEN) is a serotonin-norepinephrine-dopamine reuptake inhibitor that causes usually a mild cardiotoxicity when ingested in overdose. We report a patient who developed acute heart failure following overdose. As the toxicokinetic data suggested a prolonged metabolism, genetic polymorphisms for cytochrome P450 isoenzymes CYP2D6 and CYP2C19 were also investigated. CASE REPORT: A 34-year-old woman was admitted to the hospital 10 hours after the ingestion of an 11.25 g overdose of VEN. She was comatose and suffered two self limited seizures. The electrocardiogram showed diffuse ST segment depression, but normal QRS and QTc duration. The plasma levels on admission were 18,015 and 3,846 ng/ml for VEN and the metabolite O-desmethylvenlafaxine (ODV), respectively. The patient developed severe cardiodepression. The left ventricular shortening fraction was only 9% on echocardiography. The patient was oliguric and required continuous venovenous hemofiltration. The administration of milrinone was required for 12 days, and norepinephrine for 10 days. Left ventricular function recovered. The calculated elimination half-life was 30.8 and 72.2 hours for VEN and ODV, respectively. The patient genotype was CYP2D6*1/*5, the *5 allele corresponding to a complete deletion of CYP2D6 gene. CONCLUSIONS: Severe and sustained cardiotoxicity following VEN overdose may be related to the amount ingested, as well as to the genetic polymorphism for CYP2D6 leading to a delayed elimination of active metabolite. PMID- 22077252 TI - A fatal case of flufenoxuron-containing insecticide poisoning complicated by lactic acidosis, shock, abdominal compartment syndrome. PMID- 22077253 TI - Further case details regarding IV N-acetylcysteine overdoses. PMID- 22077255 TI - Transvaginal removal of ectopic pregnancy tissue and repair of uterine defect for caesarean scar pregnancy. PMID- 22077257 TI - Comparison of perinatal outcomes of shoulder dystocia alleviated by different type and sequence of manoeuvres: a retrospective review. PMID- 22077260 TI - Complications after surgery for deeply infiltrating pelvic endometriosis. PMID- 22077261 TI - Prostaglandin E2 vaginal gel or tablets for the induction of labour at term: a randomised controlled trial. PMID- 22077262 TI - Prostaglandin E2 vaginal gel or tablets for the induction of labour at term: a randomised controlled trial. PMID- 22077266 TI - Editors' choice. PMID- 22077267 TI - Evaluation of cost savings with ferric carboxymaltose in anemia treatment through its impact on erythropoiesis-stimulating agents and blood transfusion: French healthcare payer perspective. AB - OBJECTIVE: To evaluate the economic impact of intravenous iron (in the form of intravenous iron preparation of ferric carboxymaltose) in three different clinical settings of iron deficiency anemia: chemotherapy-induced anemia in breast cancer, chemotherapy-induced anemia in digestive cancer, and perioperative anemia in knee and hip surgery. METHODS: The economic model compared the usual therapeutic strategies of anemia without intravenous iron and strategies including intravenous iron, in each of the three clinical settings selected. Costs related to anemia treatment by erythropoiesis-stimulating agents (ESA), blood transfusion, and intravenous iron were estimated and compared inside each setting. Cost savings were calculated from the French healthcare payer perspective. Data included in the economic model were obtained from scientific literature, public health agencies, and medical experts. RESULTS: The most prominent annual cost savings were observed in chemotherapy-induced anemia in breast cancer (?997 and ?360 per patient for metastatic and non-metastatic breast cancers, respectively; global cost saving, ?33.6 million). This large impact of intravenous iron on costs was mainly explained by both a lower number of women treated and lower ESA dosing. Mean annual cost saving in digestive cancers and knee and hip surgery were estimated to ?168 and ?216 per patient and global cost savings of ?7.5 and ?12.1 million, respectively. Overall, annual cost savings in these three settings were estimated to ?53 million including ?39 million for ESA cost savings. Sensitivity analysis showed that strategies including intravenous iron remained cost-effective even with wide variations in the assumptions, particularly for cost savings on ESA. LIMITATIONS: Economic model based on literature data and expert opinions. CONCLUSIONS: The present economic model suggests that use of intravenous iron, according to recommendations of international guidelines, is cost saving, particularly in chemotherapy-induced anemia in breast cancers. PMID- 22077268 TI - Synthesis and anti-tumour activities of sulphated polysaccharide obtained from Momordica charantia. AB - A native polysaccharide (MCP2) was extracted and isolated from Momordica charantia. Four sulphated derivatives of MCP2 were prepared by chlorosulphonic acid method. The structures of the sulphated derivatives were characterised by FT IR spectra. Depending on the reaction conditions, the sulphated derivatives showed different degree of substitution (DS) ranging from 0.56 to 1.10, and different weight-average molecular mass (Mw) ranging from 7.2 to 9.3 KDa. It implied the efficient substitution of hydroxyl groups in the polysaccharides by sulphated groups with degradation. The effects of the sulphated derivatives on inhibiting the growth of HepG2 cells and Hela cells in vitro were compared with taking non-modified MCP2 as control. The sulphated derivatives inhibited the growth of HepG2 cells and Hela cells in vitro significantly, which indicated that sulphated modification could enhance the anti-tumour activity of MCP2. PMID- 22077269 TI - Acute kidney injury in a paediatric intensive care unit: comparison of the pRIFLE and AKIN criteria. AB - AIM: The purpose of our study was to evaluate and analyse the prevalence and association of acute kidney injury (AKI) as defined by paediatric Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (pRIFLE) and Acute Kidney Injury Network (AKIN) classifications in a paediatric intensive care unit (PICU). METHODS: A prospective analysis of all patients that were admitted to our PICU between June 2009 and December 2010 was performed. Patients were classified according to AKIN and pRIFLE criteria. RESULTS: One hundred and eighty-nine patients (mean age 45.9 +/- 54.7 months; 110 male, 79 female) were enrolled. Sixty-three (33.3%) patients developed AKI by AKIN criteria and 68 (35.9%) patients developed AKI by pRIFLE criteria. All patients that had AKI according to AKIN criteria also had this diagnosis with pRIFLE criteria. Five patients had developed AKI only according to pRIFLE classification, four of them owing to reduction in their estimated creatinine clearance and one of them owing to changes over 1-week period. The mean length of PICU stay was longer, need for mechanical ventilation and mortality rates were higher in patients with AKI when compared to patients without AKI. CONCLUSION: Although both pRIFLE and AKIN criteria were very helpful in the detection of patients with AKI even in the early stages of it, pRIFLE seems to be more sensitive in paediatric patients. PMID- 22077270 TI - Perspectives on family and fertility in developing countries. AB - Abstract Two aspects of the family in relation to fertility in developing countries are discussed: set stratification within the family and extended family networks. As both these are central to J. C. Caldwell's theory of fertility transition, the paper is structured as a critique of his position. Drawing on examples and data from Asia, it is argued that the causal significance of sex stratification for fertility lies in the economic risks it imposes on women, deriving from their dependence on men, rather than, as Caldwell suggests, in the disproportionate gain that men derive from their dominant position within families. While Caldwell and others associate strong extended family networks of mutual obligation and support with persistent high fertility, it is argued here that such systems should, instead, facilitate fertility decline. Close-knit and strong kin networks can be viewed as alternatives to children as sources of insurance, and may facilitate fertility decline by preventing children from becoming the focal point of parental concerns for security. PMID- 22077271 TI - Child mortality and reproductive behaviour in German village populations in the past: A micro-level analysis of the replacement effect. AB - Abstract Reproductive histories of couples married during the eighteenth and nineteenth centuries in a sample of 14 German villages are analysed in order to answer several questions regarding the relationship between child mortality and reproductive behaviour. An effort is made through selection of cases and use of multiple classification analysis to eliminate or control non-volitional or otherwise confounding influences on the relationship between a couple's experience with child mortality and their fertility. The results do not provide a decisive answer to the question of whether, under a regime of otherwise presumed natural fertility, previous experience of child mortality affected subsequent reproductive behaviour. The evidence was much clearer in indicating that behaviour consistent with replacement efforts emerged or strengthened as family limitation spread. Finally, the results indicated that though it was not necessary for overall child mortality to decline before family limitation practices were adopted, couples with the most favourable child mortality experience were most likely to practise family limitation and to reduce their fertility. Child mortality appeared at least to impede, if not totally prevent, efforts to reduce the number of children ever born or to cease childbearing at an earlier age or at a given parity. PMID- 22077272 TI - Fertility, union status and partners in the WFS Guyana and Jamaica Surveys, 1975 1976. AB - Abstract In this paper differences in the level of fertility are examined according to women's union status and their number mf partners. A number of approaches are used to analyse these relationships: differentials by current union status, the pattern of union history, and a measure of the sum synthetic composed of periods spent in each type of union, are discussed. The trend in these differentials is also analysed; using earlier surveys and census data forcomparison, we find that union status differentials have changed noticeably since the 1950s. Fertility differentials by number of partners (or the second measure proposed - number of dissolutioom) are also analysed. The data suggest that the long-existing interrelationship between union history and number of partners has now resulted in changing union status differentials within the new context of increasing use of contraception. PMID- 22077273 TI - Abortion and contraception in the Korean fertility transition. AB - Abstract In this paper the relationship between the use of abortion and contraception among married women in a society experiencing uronid decline in fertility is analysed using data from the Korean National Fertility Survey of 1974. The level and pattern of abortion before and after modern contraceptives became widely available are described, and the implications of the changing patterns of abortion and contraception are discussed. PMID- 22077274 TI - Mortality in Ghana: Evidence from the cape coast project data. AB - Abstract This paper deals with the estimation of mortality for a rural community of about 20,000 persons in the rain-forest area of south-west Ghana. Specifically, infant, child and adult mortality estimates have been obtained by the application of a wide range of direct and indirect methods of measuring mortality from the different statistics collected by a longitudinal mortality and fertility project conducted during 1974-7. It was noted that infant and childhood mortality rates obtained from death registrations were consistent with those rates yielded by pregnancy histories and child survival statistics. However, the adult mortality estimates derived from orphanhood statistics tended to be lower than those suggested by death registrations. The analysis revealed an infant mortality rate of 100 for boys and 84 for girls, equal childhood mortality rates for boys and girls (85-6), a lower expectation of life at birth for men (45.8 years) than for women (52.8), and a much more severe incidence of mortality among men aged over 40 than for women at the corresponding ages. PMID- 22077275 TI - Advances in the P/F ratio method for the analysis of birth histories. AB - Abstract One of the most frequently used indirect techniques for deriving estimates of recent fertility from simple questions in censuses and surveys is the 'P/F ratio' method. Availability of detailed birth-history data, as in the World Fertility Survey, and applications of the P/F procedure as a diagnostic tool in the evaluation of the quality of data have led to simplifications and extensions of the original method. This analysis illustrates that when complete maternity histories are available, the P/F procedure can be simplified and made more powerful by (1) calculation of P/F values from cohort-period fertility rates and (2) use of two further indexing variables, namely duration since first marriage and duration since first birth, in addition to age. More generally, the paper indicates that a set of P/F values is only one of a battery of measures which aid in the analysis of trends and errors in data from maternity histories. Illustrative examples are given from various analyses of world Fertility Survey data. Howard Goldberg has been independently pursuing an investigation of the P/F procedure by marriage duration at the Office of Population Research (Princeton University), and we have profited from recent discussions with him. We would also like to acknowledge useful comments and criticisms on earlier drafts from James Trussell and Kenneth Hill. PMID- 22077276 TI - A simple equation for estimating the expectation of life at old ages. AB - Abstract There is much direct and indirect evidence that in a number of populations the ages of older persons tend to be exaggerated, both when reported in censuses and in records of deaths. This results in overestimated expectations of life at old ages. The bias may be corrected by estimating the expectation of life at age a, e(a), from the mortality rate and growth rate at age a and above, M(a+) and r(a+), using the equation developed in this paper: 1/e(a) = M(a+) exp (beta . r(a+). M(a+)(-alpha)). For a ?, 65, alpha = 1.4 and beta = 0.0951 have been chosen. The value of the equation rests on the following: since ages of older persons tend to be exaggerated, there may be an age a such that most age transfer occurs above that age, and age transfer across the age is small or cancels, so that reasonably accurate values of M(a+) and r(a +) can be obtained, even though ages are badly reported above a. The analysis of artificial data on Gompertzian stable popultions aged over 50 and actual statistics for some selected populations has suggested that the equation provides quite accurate estimates of e(a). The equation also seems useful in closing life tables, since it provides a value of e(a) for the highest age group. PMID- 22077279 TI - Accelerated hematopoietic toxicity by high energy (56)Fe radiation. AB - PURPOSE: There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to gamma or X-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater. METHODS: C57BL/6J mice were irradiated with (56)Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of gamma rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of (56)Fe ions were compared to gamma rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival. RESULTS: Although onset was more rapid, (56)Fe ions were only slightly more toxic than gamma rays or protons with lethal dose (LD)(50/30) (a radiation dose at which 50% lethality occurs at 30 day) values of 5.8, 7.25, and 6.8 Gy, respectively, with relative biologic effectiveness for (56)Fe ions of 1.25 and 1.06 for protons. CONCLUSIONS: (56)Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to gamma rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity. PMID- 22077280 TI - An efficient route to tetrahydroindeno[2,1-b]pyrroles via a base-promoted reaction of (E)-2-alkynylphenylchalcone with 2-isocyanoacetate. AB - A base-promoted cascade reaction of (E)-2-alkynylphenylchalcone with 2 isocyanoacetate provides a novel and efficient route for the synthesis of tetrahydroindeno[2,1-b]pyrroles. The reaction proceeds smoothly in air under mild conditions with high efficiency. PMID- 22077281 TI - DNA concentration modulation on supported lipid bilayers switched by surface acoustic waves. AB - Spatially addressable arrays of molecules embedded in or anchored to supported lipid bilayers are important for on-chip screening and binding assays; however, methods to sort or accumulate components in a fluid membrane on demand are still limited. Here we apply in-plane surface acoustic shear waves (SAWs) to laterally accumulate double-stranded DNA segments electrostatically bound to a cationic supported lipid bilayer. The fluorescently labeled DNA segments are found to segregate into stripe patterns with a spatial frequency corresponding to the periodicity of the standing SAW wave (~10 MUm). The DNA molecules are accumulated 10-fold in the regions of SAW antinodes. The superposition of two orthogonal sets of SAW sources creates checkerboard like arrays of DNA demonstrating the potential to generate arrayed fields dynamically. The pattern relaxation time of 0.58 s, which is independent of the segment length, indicates a sorting and relaxation mechanism dominated by lipid diffusion rather than DNA self-diffusion. PMID- 22077282 TI - Cosolute paramagnetic relaxation enhancements detect transient conformations of human uracil DNA glycosylase (hUNG). AB - The human DNA repair enzyme uracil DNA glycosylase (hUNG) locates and excises rare uracil bases that arise in DNA from cytosine deamination or through dUTP incorporation by DNA polymerases. Previous NMR studies of hUNG have revealed millisecond time scale dynamic transitions in the enzyme-nonspecific DNA complex, but not the free enzyme, that were ascribed to a reversible clamping motion of the enzyme as it scans along short regions of duplex DNA in its search for uracil. Here we further probe the properties of the nonspecific DNA binding surface of {(2)H(12)C}{(15)N}-labeled hUNG using a neutral chelate of a paramagnetic Gd(3+) cosolute (Gd(HP-DO3A)). Overall, the measured paramagnetic relaxation enhancements (PREs) on R(2) of the backbone amide protons for free hUNG and its DNA complex were in good agreement with those calculated based on their relative exposure observed in the crystal structures of both enzyme forms. However, the calculated PREs systematically underestimated the experimental PREs by large amounts in discrete regions implicated in DNA recognition and catalysis: active site loops involved in DNA recognition (268-274, 246-250), the uracil binding pocket (143-148, 169-170), a transient extrahelical base binding site (214-216), and a remote hinge region (129-132) implicated in dynamic clamping. These reactive hot spots were not correlated with structural, hydrophobic, or solvent exchange properties that might be common to these regions, leaving the possibility that the effects arise from dynamic sampling of exposed conformations that are distinct from the static structures. Consistent with this suggestion, the above regions have been previously shown to be flexible based on relaxation dispersion measurements and course-grained normal-mode analysis. A model is suggested where the intrinsic dynamic properties of these regions allows sampling of transient conformations where the backbone amide groups have greater average exposure to the cosolute as compared to the static structures. We conclude that PREs derived from the paramagnetic cosolute reveal dynamic hot spots in hUNG and that these regions are highly correlated with substrate binding and recognition. PMID- 22077283 TI - Synchronous fluorescence as a rapid method for the simultaneous determination of folic acid and riboflavin in nutritional beverages. AB - A rapid synchronous spectrofluorimetric method was first developed for the simultaneous determination of folic acid and riboflavin in nutrimental beverages. Folic acid could be detected by using H(2)O(2) plus Cu(II) as oxidation system to produce pterine-6-carboxylic acid, which had strong fluorescence in aqueous solution, and riboflavin itself was obviously fluorescent. Various operational parameters were thoroughly discussed in terms of their effects on the fluorescence signals, including instrumental parameters, concentration of the oxidation system, and pH. Under optimum conditions, the calibration curves were linear in the ranges of 100-250 MUg/L for folic acid and 1-250 MUg/L for riboflavin, and the detection limits were 2.0 and 0.014 MUg/L, respectively. In addition, this method was applied to the determination of folic acid and riboflavin in nutrimental beverages with satisfactory results. PMID- 22077284 TI - Modeling and verification of melanin concentration on human skin type. AB - Lasers are used in the minimalistic or noninvasive diagnosis and treatment of skin disorders. Less laser light reaches the deeper skin layers in dark skin types, due to its higher epidermal melanin concentration compared with lighter skin. Laser-tissue interaction modeling software can correct for this by adapting the dose applied to the skin. This necessitates an easy and reliable method to determine the skin's type. Noninvasive measurement of the skin's melanin content is the best method. However, access to samples of all skin types is often limited and skin-like phantoms are used instead. This study's objective is to compare experimentally measured absorption features of liquid skin-like phantoms representing Skin Types I-VI with a realistic skin computational model component of ASAP((r)). Sample UV-VIS transmittance spectra were measured from 370 to 900 nm and compared with simulated results from ASAP((r)) using the same optical parameters. Results indicated nonmonotonic absorption features towards shorter wavelengths, which may allow for more accurate ways of determining melanin concentration and expected absorption through the epidermal layer. This suggests possible use in representing optical characteristics of real skin. However, a more comprehensive model and phantoms are necessary to account for the effects of sun exposure. PMID- 22077285 TI - Relation of high-pass filtered unipolar electrograms to bipolar electrograms during ventricular mapping. AB - BACKGROUND: A filtered bipolar electrogram (EG) amplitude <1.5 mV is a robust indicator of relatively dense scar, but is influenced by the wavefront direction. Unipolar recordings are not subject to directional influence. We hypothesized that high-pass filtered unipolar EGs would provide similar information to bipolar EGs, without potential errors related to wavefront direction. METHODS: Simultaneous bipolar filtered at 30-500 Hz and unipolar (high-pass filtered at 30 Hz) signals were recorded during ventricular voltage maps in 24 patients (group A). In five subsequent patients, low voltage surface areas were compared in electroanatomic maps (group B). RESULTS: Of 2,789 mapping points in group A, filtered unipolar EG amplitude correlated well with bipolar EG amplitude. Agreement of filtered unipolar recordings in classifying sites as >1.5 mV or <1.5 mV with bipolar EG amplitude was 83%. Discordance was due to unipolar > bipolar amplitude at 83% of the discordant sites, consistent with possible reduction of bipolar amplitude due to direction dependence. Discordance was more frequent during epicardial than endocardial mapping. Double potentials were more frequently observed in bipolar than in unipolar recordings (3.2% vs 1.8%, P < 0.0001). In group B, the mean low-voltage surface area (<1.5 mV) was 70.1 +/- 48.9 cm(2) for bipolar and 61.3 +/- 52.2 cm(2) for filtered unipolar EG maps. CONCLUSION: Direction dependent effects on bipolar EG amplitude may influence the identification of substrate for arrhythmias. High-pass filtered unipolar EGs might be a reasonable alternative to bipolar recordings for creation of voltage maps. PMID- 22077286 TI - Color tuning in binding pocket models of the chlamydomonas-type channelrhodopsins. AB - We examined the shift of absorption maxima between the chlamydomonas-type channelrhodopsins (ChRs) and bacteriorhodopsin (BR). Starting from the BR X-ray structure, we modeled the color tuning in the binding pockets of the ChRs by mutating up to 28 amino acids in the vicinity of the chromophore. By applying the efficient self-consistent charge density functional tight binding (SCC-DFTB) method in a quantum mechanical/molecular mechanical (QM/MM) framework, including explicit polarization and calculating excitation energies with the semiempirical OM2/MRCI method and the ab initio SORCI method, we have shown that multiple mutations in the binding pocket of BR causes large hypsochromic shifts that are of the same order as the experimentally observed shifts of the absorption maxima between BR and the ChRs. This study further demonstrates that mutations in the proximity of the Schiff base and complex counterion lead to a stronger but more flexible interaction with the retinal, which could serve as a possible explanation for the spectral patterns found in the ChRs. PMID- 22077287 TI - Incorporation of amphiphilic ruthenium(II) ammine complexes into Langmuir Blodgett thin films with switchable quadratic nonlinear optical behavior. AB - Nine nonlinear optical (NLO) chromophores with pyridinium electron acceptors have been synthesized by complexing new proligands with {Ru(II)(NH(3))(5)}(2+) electron-donor centers. The presence of long alkyl/fluoroalkyl chain substituents imparts amphiphilic properties, and these cationic complexes have been characterized as their PF(6)(-) salts by using various techniques including electronic absorption spectroscopy and cyclic voltammetry. Each complex shows three reversible/quasireversible redox processes; a Ru(III/II) oxidation and two ligand-based reductions. The energies of the intense visible d -> pi* metal-to ligand charge-transfer (MLCT) absorptions correlate to some extent with the ligand reduction potentials. (1)H NMR spectroscopy also provides insights into the relative electron-withdrawing strengths of the new ligands. Single crystal X ray structures have been determined for two of the proligand salts and one complex salt, [Ru(II)(NH(3))(5)(4-C(16)H(33)PhQ(+))]Cl(3).3.25H(2)O (PhQ(+) = N phenyl-4,4'-bipyridinium), showing centrosymmetric packing structures in each case. The PF(6)(-) analogue of the latter complex has been used to deposit reproducibly high-quality, multilayered Langmuir-Blodgett (LB) thin films. These films show a strong second harmonic generation (SHG) response from a 1064 nm laser; their MLCT absorbance increases linearly with the number of layers (N) and I(2omega)/I(omega)(2) (I(2omega) = intensity at 532 nm; I(omega) = intensity at 1064 nm) scales quadratically with N, consistent with homogeneous deposition. LB films on indium tin oxide (ITO)-coated glass show electrochemically induced switching of the SHG response, with a decrease in activity of about 50% on Ru(II) -> Ru(III) oxidation. This effect is reversible, but reproducible over only a few cycles before the signal from the Ru(II) species diminishes. This work extrapolates our original solution studies (Coe, B. J. et al. Angew. Chem., Int. Ed.1999, 38, 366) to the first demonstration of redox-switching of NLO activity in a molecular material. PMID- 22077288 TI - Differentiating infection from vaccination in foot-and-mouth disease. PMID- 22077289 TI - Differentiating foot-and-mouth disease virus-infected from vaccinated animals with baculovirus-expressed specific proteins. AB - Abstract We had shown in preliminary studies with a small number of animals that antibodies against 2C could be detected in cattle and pigs which had been infected with FMDV but not in animals which had been vaccinated against the disease. To determine whether this test was generally applicable, seta from several hundred animals which had been vaccinated with different products in many countries have been tested in an ELISA using baculovirus expressed 2C. Our results show that only 1-2% of the sera gave a positive reaction by this method. In contrast, 100% of sera from convalescent animals gave a positive reaction. To be useful in differentiating between convalescent and vaccinated animals it is necessary to know how long these antibodies can be detected by our ELISA. We have determined the levels of antibodies against 2C and also other virus-specific proteins which are present in cattle and pigs following infection with FMDV. Our results show that levels of anti-3ABC antibodies could be detected by ELISA with baculovirus-expressed protein up to one year after infection. In contrast, the levels of anti-2C antibodies fell more rapidly than those against 3ABC indicating that the latter protein may be preferable for detecting convalescent animals. Nevertheless, we envisage that the final test format should include several virus specific proteins to determine accurately the immune status of an animal. PMID- 22077290 TI - Cattle response to foot-and-mouth disease virus nonstructural proteins as antigens within vaccines produced using different concentrations. AB - Abstract Four groups of ten nine-month-old Nelore heifers were used for this study. Each group received one of four foot-and-mouth disease (FMD) trivalent vaccines for the duration of the experiment. The four vaccine formulations (Normal, 2X, 4X and 8X) differed in 140S content to determine the serological reactivities to FMD virus (FMDV) nonstructural proteins 2C, 3ABC and 3D. Vaccination was by the intramuscular administration of vaccine on day 0, 180 and 360. Bleedings were done at 30 days post vaccination (dpv), 90 dpv, 30 days post revaccination (dpr), 90 dpr, and 30 days post third administration (dprr). There was a general tendency to have higher mean 3D responses with increased vaccine application but not with increased concentration of antigen. With 2C and 3ABC this tendency was not seen, neither with repeated application of vaccine nor with increased antigen concentration. All individual animal observations to 2C and 3ABC remained within three standard deviations of the average observed for naive bovids. Percent of positive (PP) reactions was determined using an ELISA for nonstructural proteins 2C, 3ABC and 3D expressed in baculovirus as previously described. A value of >25 PP to 2C or 3ABC could be considered as an indication of previous infection or of the presence of viral activity. PP results between 18 and 25 PP suggest viral activity and animals should be retested. Those responses below 15 PP are suggestive of vaccination or naive status. As diagnosis in the laboratory is not divorced from the field epidemiological scene, the intermediate zone between 10 and 20 PP should be considered and acted upon according to the overall zoosanitary situation of that country or region and the purposes of the ongoing FMD control efforts. PMID- 22077291 TI - Blocking ELISAs using the FMDV non-structural proteins 3D, 3AB, and 3ABC produced in the baculovirus expression system. PMID- 22077292 TI - Diagnostic potential of Mab-based ELISAs for antibodies to non-structural proteins of foot-and-mouth disease virus to differentiate infection from vaccination. AB - Abstract This paper summarises the development of monoclonal antibody (Mab) based immunoassays measuring antibodies to non-structural proteins of FMDV to differentiate infection from vaccination. Of the three non-structural proteins 2C, 3C and 3ABC evaluated in this study, the polypeptide 3ABC was the most immunogenic. Three ELISAs for the detection of antibodies to 3ABC were developed. Two assays rely on the competition of test sera against either a anti-3A Mab or against antisera to 3ABC raised in rabbits and guinea-pigs. The third, 3ABC Mat ELISA, based on the direct binding of antibodies to the 3ABC trapped by a specific Mab, provided the best combination of specificity and sensitivity. The 3ABC Mat-ELISA was extensively validated for cattle, either in experimental and in field conditions, showing specificity of 99% in vaccinated and in naive cattle and the capacity to detect silent infections in FMD-vaccinated populations. The test showed similar specificity and sensitivity in experimentally vaccinated and infected sheep. PMID- 22077293 TI - The possible use of native foot-and-mouth disease nonstructural protein 3A in a serological screening test. AB - Abstract ELISA's for antibodies to non-structural proteins of foot-and-mouth disease developed to date use recombinant proteins as antigens. To compare the antibody response to recombinant antigen and native antigen we developed an antigen capture ELISA for foot-and-mouth protein 3A. The concentration of 3A protein in virus cultures was significantly higher in the cell debris than in the supernatant, which made it possible to use proteins directly eluted from cells separated from a virus culture using Filteraid. The antigen was trapped between one monoclonal antibody coated to the plate, and a second monoclonal antibody conjugated with horseradish peroxidase. The reaction of the second (conjugated) monoclonal antibody could be blocked by several post-infection sera. Further research has to be performed to determine whether or not this method can result in a reproducible serological test. PMID- 22077294 TI - Application of RT-PCR and nucleotide sequencing in foot-and-mouth disease diagnosis. PMID- 22077296 TI - Detection of foot-and-mouth disease by reverse transcription polymerase chain reaction and virus isolation in contact sheep without clinical signs of foot-and mouth disease. AB - Summary Two non-vaccinated sheep were experimentally, infected with FMDV and one day later 4 other sheep were brought in contact. Although the contact sheep showed no clinical signs, serology indicated that all sheep became infected. Various secretion samples, taken over a period of at least one month, and various tissue samples were examined for the presence of FMDV by RT-PCR and by virus isolation. FMDV was most often found in saliva (mouth swabs), followed by nasal secretion and sera. Faecal material, wool and milk were less suitable. The period of detection with the highest frequency of positive isolations was between 2 to 4 days pi for the infected sheep and between 5 to 10 days pc for the contact animals. It was established that in subclinically infected sheep, with a very low amount of virus present, FMD viral RNA could be detected by a sensitive RT-PCR ELISA although virus isolation and standard RT-PCR remained negative. Moreover there was some evidence of active spreading of FMDV from the contact sheep to two sentinel pigs. This indicates that serologically positive contact sheep without clinical signs may be considered as a danger for the transmission of FMDV. PMID- 22077295 TI - RT-PCR in foot-and-mouth. AB - Summary A RT-PCR assay for the specific detection of RNA sequences from foot and-mouth disease virus (FMDV) has been developed. The procedure permits also the detection of sequences that correlate with established FMDV serotypes. A computer program that allows selection of genotype-specific primers for RT-PCR amplification was used for the identification of FMDV specific sequences for PCR amplification on RNA replicase (3D) gene regions. Specific, rapid and highly sensitive detection was achieved for a wide collection of RNA samples from FMDV types C, A and O, either purified from tissue culture or extracted from lesions of infected animals. Similarly, serotype-specific primers were designed to amplify the carboxy-terminal end of the VP1 gene of FMDV types either C, A or O. The results of PCR amplification of diffefent FMDV RNAs using type-specific primers are in agreement with the serological typing of the corresponding viruses. A combination of this approach with a simplified sample processing, carried out following direct adsorption of viral suspensions to microtiter plates, provides a rapid, reliable method of viral diagnosis. PMID- 22077298 TI - A mad mayor of Fremantle: the mysterious illness of Edward Davies. AB - OBJECTIVE: The aim of this paper is to illustrate how a person's standing in a small, close-knit community can distort local medical and legal attitudes to their diagnosis. We examined various historical texts describing Edward Davies (1855?1904), Mayor of Fremantle, and the medical, legal and family responses to his illness. CONCLUSIONS: When Davies developed an apparently serious mental illness, his family was able to keep this behaviour hidden for some time. However, when evidence of his illness finally erupted into the public eye, it led to a ground-breaking 1903 case in the WA Supreme Court in Lunacy. It is clear that Davies? defenders wanted him to be diagnosed and treated as an alcoholic, when in fact he may have had late onset psychosis, complicated by alcohol abuse. With the increasing amount of historical material available through Australian digitized newspaper collections, new scope is opening up for retrospective diagnosis. PMID- 22077299 TI - Revisiting the hypothesis-driven interview in a contemporary context. AB - OBJECTIVE: The "hypothesis-driven interview" was articulated by George Engel as a method of raising and testing hypotheses in the process of building a biopsychosocial formulation and determining the most likely diagnosis. This interview was a forerunner of the modern medical interview as well as the contemporary psychiatric assessment. The objective of this article is to describe the hypothesis-driven interview and to explore its relationship with the contemporary medical interview. METHOD: The literature on the medical and hypothesis-driven interview was reviewed. Key features of each were identified. RESULTS: The hypothesis-driven interview shares much with the contemporary medical interview. In addition, it enhances the application of communication skills and allows the interviewer to develop a formulation during the course of the assessment. CONCLUSION: The hypothesis-driven interview is well suited to the aims of a contemporary psychiatric assessment. PMID- 22077300 TI - Consumer participation in service evaluation and quality improvement: key ingredients for a system to deliver national indicators. AB - OBJECTIVES: The aim of this paper is to describe the fundamental components of a system to ensure consumer participation in mental health service evaluation and quality improvement. CONCLUSIONS: The seven fundamental components identified provide the basis for a system to deliver national indicators for consumer participation in quality improvement under the National Health Performance domain of "responsiveness to consumers". The MH-CoPES Framework satisfies these criteria and may be drawn upon as the basis for developing local systems for consumer participation in quality improvement within mental health services. PMID- 22077301 TI - Hospital admissions for obsessive-compulsive disorder in NSW, 1997 to 2010. AB - OBJECTIVES: To assess the characteristics of admissions to NSW hospitals with a diagnosis of obsessive-compulsive disorder (OCD). METHOD: Assessment of administrative data from all NSW hospital admissions from 1997 to 2010. RESULTS: The average admission rate for a primary diagnosis of OCD was 1.5 per 100,000 population. This rate increased over the period assessed. OCD was much more common as a secondary diagnosis (6.1 per 100,000 population), often occurring with affective disorders in adults and other anxiety disorders in children. Adults admitted with OCD had an average length of stay of 24 days. CONCLUSIONS: Although hospital admissions of patients with OCD are uncommon, the high rates of comorbidity and increasing rates of admission alert us to the significance of screening patients for OCD and being able to offer outpatient treatment. PMID- 22077302 TI - The validity and utility of risk assessment for inpatient suicide. AB - OBJECTIVE: It is widely assumed that identifying clinical risk factors can allow us to determine which patients are at high risk of suicide while in hospital, and that identifying those patients can help prevent inpatient suicide. We aimed to examine the validity and utility of categorizing psychiatric patients to be at either high or low risk of committing suicide while in hospital. METHOD: The assumption that high-risk categorizations are valid was examined by comparing factors included in high-risk models derived from individual studies of inpatient suicide with the results of a meta-analysis of factors associated with inpatient suicide. A valid high-risk model was then applied to a hypothetical clinical setting in order to test the assumption that high-risk categorizations are useful. RESULTS: The existing models for assessing whether inpatients are at high risk of suicide all include one or more factors that were not found to be associated with inpatient suicide by meta-analysis and were probably chance associations. Depressed mood and a prior history of self-harm are the only well established independent risk factors for inpatient suicide. Using these risk factors to classify patients as being at high or low risk would prevent few, if any, suicides, and would come at a considerable cost in terms of more restrictive care of many patients and the reduced level of care available to the remaining patients. CONCLUSIONS: Risk categorization of individual patients has no role to play in preventing the suicide of psychiatric inpatients. PMID- 22077303 TI - Comment: To collude or not to collude with crimes against humanity - the question of Adam Czerniakow's suicide. PMID- 22077304 TI - Early onset eating disorders in male adolescents: a series of 10 inpatients. AB - OBJECTIVE: This case series aims to describe the demographic and clinical features of male inpatients with early onset eating disorders. METHOD: Retrospective review was made of medical files of male patients treated for eating disorders at two children's hospitals over a 2 year period, with an onset of eating disorder before age 14 years, presenting for index admission. Demographic characteristics, DSM-IV diagnosis, clinical characteristics and treatment received were reviewed. RESULTS: Ten male patients with a median age of 12.8 years (range 10.2 to 13.5) were identified; three met the full criteria for anorexia nervosa (AN) and four met all except the weight criterion. There was high psychiatric comorbidity: four with a major depressive episode, seven an anxiety disorder, three with obsessive-compulsive disorder (OCD) symptoms. Seven engaged in over-exercise. Seven were treated with an antidepressant, and five with an atypical antipsychotic; six required nasogastric tube (NGT) feeding. CONCLUSION: A minority of patients met full diagnostic criteria for AN, with many not meeting weight criteria despite medical instability. The main clinical features were food restriction, over-exercise and psychiatric comorbidity. Treatment with antidepressants, antipsychotics and NGT feeding was frequent. Future prospective studies could help identify gender-specific features as well as benefits and potential side effects of pharmacotherapy in this age group. PMID- 22077306 TI - Consultation-liaison psychiatry and prevention of severe neuroleptic sensitivity reactions in dementia with Lewy bodies. PMID- 22077307 TI - Health and wellbeing of the invisible: homeless women with young children. PMID- 22077308 TI - Inadequate psychological assessment for female to male gender reassignment. PMID- 22077309 TI - Yoga and mental health. PMID- 22077314 TI - Correlation of L-type amino acid transporter 1 and CD98 expression with triple negative breast cancer prognosis. AB - Triple negative breast cancer (TNBC) is a heterogeneous, aggressive cancer for which there is no effective chemotherapy or targeted therapy. We aimed to evaluate L-type amino acid transporter (LAT) 1 and CD98 expression immunohistochemically in patients with breast cancer, especially TNBC. Out of 129 patients, LAT1 was positive in 56 patients (43.4%), and CD98 was positive in 41 patients (31.8%). The positive ratio of LAT1 expression in luminal A cases was 7.9%, 30.0% in luminal B cases, 71.4% in HER2 cases and 64.0% in TN cases. HER2 and TN subtypes expressed LAT1 and CD98 at higher levels than luminal A and B subtypes (both P < 0.001). LAT1 and CD98 expression correlated with tumor size (LAT1, P = 0.010; CD98, P = 0.007), nuclear grade (LAT1, P < 0.001; CD98, P < 0.001) and Ki67 labeling index (LAT1, P < 0.001; CD98, P = 0.001). LAT1 and CD98 expression was negatively associated with ER and PgR (both P < 0.001). In TNBC, the 5-year disease-free rate of CD98+ (63.6%) or LAT1+/CD98+ (61.9%) patients was significantly worse than that of CD98- (89.3%) patients or those with no co expression of LAT1 and CD98 (89.7%), respectively (P = 0.014, P = 0.009). The 5 year survival rates of CD98 positive/negative patients were 77.3% and 100% (P = 0.050), respectively, whereas that of patients with LAT1+/CD98+ (76.2%) was significantly worse (100%) (P = 0.040). Multivariate analysis confirmed that CD98+ or LAT1+/CD98+ expression were risk factors for relapse in TNBC (P = 0.023, P = 0.019). Thus, in the present study we show that LAT1 and CD98 expression are prognostic factors. Inhibition of these proteins might provide a new therapeutic strategy in TNBC. PMID- 22077315 TI - A headache which leaves you feeling bruised. PMID- 22077316 TI - Phenotyping sleep. PMID- 22077317 TI - Histopathological and behavioral effects of immediate and delayed hemorrhagic shock after mild traumatic brain injury in rats. AB - The purpose of this study was to investigate the increased susceptibility of the brain, after a controlled mild cortical impact injury, to a secondary ischemic insult. The effects of the duration and the timing of the secondary insult after the initial cortical injury were studied. Rats anesthetized with isoflurane underwent a 3 m/sec, 2.5-mm deformation cortical impact injury followed by hypotension to 40 mm Hg induced by withdrawing blood from a femoral vein. The duration of hypotension was varied from 40 to 60 min. The timing of 60 min of hypotension was varied from immediately post-injury to 7 days after the injury. Outcome was assessed by behavioral tasks and histological examination at 2 weeks post-injury. A separate group of animals underwent measurement of the acute physiology including mean blood pressure (MAP), intracranial pressure (ICP), and cerebral blood flow (CBF) using a laser Doppler technique. Increasing durations of hypotension resulted in marked expansion of the contusion, from 6.5+/-1.8 mm3 with sham hypotension to 27.1+/-3.9 mm3 with 60 min of hypotension. This worsening of the contusion was found only when then hypotension occurred immediately after injury or at 1 h after injury. CA3 neuron loss followed a similar pattern, but the injury group differences were not significant. Motor tasks, including beam balance and beam walking, were significantly worse following 50 and 60 min of hypotension. Performance on the Morris water maze task was also significantly related to the injury group. Studies of the acute cerebral hemodynamics demonstrated that CBF was significantly more impaired during hypotension in the animals that underwent the mild TBI compared to those that underwent sham TBI. The perfusion deficit was worst at the impact site, but also significant in the pericontusional brain. With 50 and 60 min of hypotension, CBF did not recover following resuscitation at the impact site, and recovered only transiently in the pericontusional brain. These results demonstrate that mild TBI, like more severe levels of TBI, can impair the brain's ability to maintain CBF during a period of hypotension, and result in a worse outcome. PMID- 22077318 TI - Influences of incorporating detoxified Jatropha curcas kernel meal in common carp (Cyprinus carpio L.) diet on the expression of growth hormone- and insulin-like growth factor-1-encoding genes. AB - Jatropha curcas is a drought-resistant shrub or small tree widespread all over the tropics and subtropics. The use of J. curcas (L) kernel meal in fish feed is limited owing to the presence of toxic and antinutritional constituents. In this study, it was detoxified using heat treatment and organic solvent extraction method. The detoxification process was carried out for 60 min to obtain the detoxified meal. Cyprinus carpio L. fingerlings (n = 180; avg. wt. 3.2 +/- 0.07 g) were randomly distributed in five treatment groups with four replicates and fed isonitrogenous diets (crude protein 38%) for 8 weeks. The inclusion levels of the detoxified Jatropha kernel meal (DJKM) and soybean meal (SBM) were as follows: control diet was prepared with fish meal (FM) and wheat meal, without any DJKM and SBM; diets S(50) and J(50) : 50% of FM protein replaced by SBM and DJKM respectively; diets S(75) and J(75) : 75% of FM protein replaced by SBM and DJKM respectively. Highest body mass gain and insulin-like growth factor-1 (IGF 1) gene expression in brain, liver and muscle were observed for the control group, which were statistically similar to those for J(50) group and significantly (p < 0.05) higher than for all other groups, whereas growth hormone gene expression in brain, liver and muscle exhibited opposite trend. Insulin-like growth factor-1 concentration in plasma did not differ significantly among the five groups. Conclusively, growth performance was in parallel with IGF-1 gene expression and exhibited negative trend with GH gene expression. PMID- 22077319 TI - Augmentation of clozapine with a second antipsychotic - a meta-analysis. AB - OBJECTIVE: To examine using meta-analysis the effect of adding a second antipsychotic to established clozapine monotherapy. METHOD: A literature search was conducted in April 2011, and randomised placebo-controlled double-blind studies were identified. We performed a meta-analysis of efficacy (as standardised mean difference) and tolerability (withdrawals from trials) and a regression analysis of duration of study versus effect size. We also examined publication bias using funnel-plot analysis. RESULTS: Overall, 14 studies were included (734 subjects). Individual study numbers ranged from 10 to 207 (mean 52.6, median 40). Augmentation of clozapine with a second antipsychotic conferred a small benefit over placebo (effect size -0.239 (95% CI: -0.452, -0.026); P = 0.028). Meta-regression of the effect of length of treatment on effect size showed no relationship (P = 0.254). The risk of discontinuing antipsychotic augmentation was no greater than the risk of discontinuing placebo (RR = 1.20, 95% CI 0.80-1.82). There was no evidence of publication bias. CONCLUSION: Augmentation with a second antipsychotic is modestly beneficial in patients not responding fully to clozapine. Tolerability seems not to be adversely affected, at least in the short term. Longer studies do not appear to increase the probability of showing positive effects for augmentation. PMID- 22077320 TI - Molecular responses of human lung epithelial cells to the toxicity of copper oxide nanoparticles inferred from whole genome expression analysis. AB - This study proposes a molecular mechanism for lung epithelial A549 cell response to copper oxide nanoparticles (CuO-NPs) related to Cu ions released from CuO-NPs. Cells that survived exposure to CuO-NPs arrested the cell cycle as a result of the downregulation of proliferating cell nuclear antigen (PCNA), cell division control 2 (CDC2), cyclin B1 (CCNB1), target protein for Xklp2 (TPX2), and aurora kinase A (AURKA) and B (AURKB). Furthermore, cell death was avoided through the induced expression of nuclear receptors NR4A1 and NR4A3 and growth arrest and DNA damage-inducible 45 beta and gamma (GADD45B and GADD45G, respectively). The downregulation of CDC2, CCNB1, TPX2, AURKA, and AURKB, the expressions of which are involved in cell cycle arrest, was attributed to Cu ions released from CuO NPs into medium. NR4A1 and NR4A3 expression was also induced by Cu ions released into the medium. The expression of GADD45B and GADD45G activated the p38 pathway that was involved in escape from cell death. The upregulation of GADD45B and GADD45G was not observed with Cu ions released into medium but was observed in cells exposed to CuO-NPs. However, because the expression of the genes was also induced by Cu ion concentrations higher than that released from CuO-NPs into the medium, the expression appeared to be triggered by Cu ions released from CuO-NPs taken up into cells. We infer that, for cells exposed to CuO-NPs, those able to make such a molecular response survived and those unable to do so eventually died. PMID- 22077321 TI - Comparison of intracytoplasmic sperm injection outcomes between spermatozoa retrieved from testicular biopsy and from ejaculation in cryptozoospermic men. AB - The infrequent presence of spermatozoa in cryptozoospermic men ejaculate is a limiting factor in the treatment of them. Sometimes, this consideration impels us to apply meticulous microscopic search in ejaculate or testicular sperm extraction (TESE) method. The aim of this study was to assess putative effectiveness of sperm origin, ejaculated or testicular, in cryptozoospermia treatment. In this context, were evaluated intracytoplasmic sperm injection (ICSI) outcomes in two parameters including fertilisation rate (2PN) and embryo quality, independently. We compared the outcome in two groups: patients who underwent ejaculate/ICSI and ones who underwent TESE/ICSI process. Nineteen ICSI cycles performed with testicular spermatozoa and the rest of cycles (n = 208) carried out with ejaculated spermatozoa. Result analysis showed similar fertilisation rate between testicular and ejaculated spermatozoa (respectively, 60% versus 68%, P >= 0.05). Also, on the other hand, embryo quality did not show significant differences between two groups, except grade A with low significance. With regard to almost equal performance of both methods in results and being invasive of TESE as surgical sperm retrieval method, the use of ejaculated sperm more than testicular sperm should be recommended in patients with cryptozoospermia whenever possible. PMID- 22077322 TI - Microbialites and global environmental change across the Permian-Triassic boundary: a synthesis. AB - Permian-Triassic boundary microbialites (PTBMs) are thin (0.05-15 m) carbonates formed after the end-Permian mass extinction. They comprise Renalcis-group calcimicrobes, microbially mediated micrite, presumed inorganic micrite, calcite cement (some may be microbially influenced) and shelly faunas. PTBMs are abundant in low-latitude shallow-marine carbonate shelves in central Tethyan continents but are rare in higher latitudes, likely inhibited by clastic supply on Pangaea margins. PTBMs occupied broadly similar environments to Late Permian reefs in Tethys, but extended into deeper waters. Late Permian reefs are also rich in microbes (and cements), so post-extinction seawater carbonate saturation was likely similar to the Late Permian. However, PTBMs lack widespread abundant inorganic carbonate cement fans, so a previous interpretation that anoxic bicarbonate-rich water upwelled to rapidly increase carbonate saturation of shallow seawater, post-extinction, is problematic. Preliminary pyrite framboid evidence shows anoxia in PTBM facies, but interbedded shelly faunas indicate oxygenated water, perhaps there was short-term pulsing of normally saturated anoxic water from the oxygen-minimum zone to surface waters. In Tethys, PTBMs show geographic variations: (i) in south China, PTBMs are mostly thrombolites in open shelf settings, largely recrystallised, with remnant structure of Renalcis group calcimicrobes; (ii) in south Turkey, in shallow waters, stromatolites and thrombolites, lacking calcimicrobes, are interbedded, likely depth-controlled; and (iii) in the Middle East, especially Iran, stromatolites and thrombolites (calcimicrobes uncommon) occur in different sites on open shelves, where controls are unclear. Thus, PTBMs were under more complex control than previously portrayed, with local facies control playing a significant role in their structure and composition. PMID- 22077323 TI - Enhanced transdermal delivery of 18beta-glycyrrhetic acid via elastic vesicles: in vitro and in vivo evaluation. AB - OBJECTIVE: The aim of this work was to develop an elastic vesicular formulation to enhance the skin permeation of a poorly water-soluble 18beta-glycyrrhetic acid (GA) and treat dermatitis. METHODS: Elastic vesicles of GA were prepared by the film method with high pressure homogenizer and characterized by storage stability. In vitro permeation studies were carried on rat skin using Franz diffusion cell. In vivo skin deposition of GA was studied using HPLC assay. Chronic allergic contact dermatitis model was built to evaluate pharmacodynamic of GA elastic vesicles. RESULTS: The GA elastic vesicles developed have high flexibility and the storage stability was at least for 6 months at 4 degrees C and for 4 months at 25 degrees C. In vitro cumulative penetration of GA from elastic vesicles within 8 hours was 5.3-fold and 23.2-fold higher than that of conventional liposomes and saturated solution, respectively. After non-occlusive application to mice ears in vivo, skin deposition of GA increased immediately and reached the C(max) at 3 h (1.95 +/- 0.32 ug/cm2) and still detected, even after 16 hours GA removed. In vivo anti-inflammatory activity study, GA elastic vesicles showed significant reduction in ear thickness and mass (25.52% and 49.23%) (P < 0.05). The suppressive activity was comparable to that of positive control group (Triamcinolone Acetonide and Econazole Nitrate cream in market), while few side effects were observed in present model. CONCLUSION: The results suggested that of GA elastic vesicular was safe and effective in treatment of contact dermatitis by transdermal administration. PMID- 22077324 TI - Transient changes of intraocular pressure and anterior segment configuration after diagnostic mydriasis with 1% tropicamide in children. AB - BACKGROUND: This study investigated the association of transient changes in intraocular pressure (IOP) with changes in the anterior chamber configuration in children after diagnostic mydriasis with 1% tropicamide. METHODS: In this prospective case-control study, 163 hospital clinic-based samples of unrelated children with or without myopia were enrolled. Complete ophthalmological examinations, including visual acuities, cycloplegic refraction, slitlamp examination, fundus examination, IOP, axial length measurement and Pentacam examination were performed. RESULTS: Lens thickness in emmetropic children was significantly greater than in myopic children of both genders, both before and after mydriasis. In a comparison of the biometric differences before and after mydriasis, IOP was not different, but the lens thickness after mydriasis was significantly less in myopic and emmetropic children of both genders. The mean anterior chamber angle, anterior chamber depth and anterior chamber volume significantly increased after mydriasis in myopic and emmetropic children of both genders. These parameters were not related to the changes of IOP under multiple regression analysis. There were no statistically significant differences between groups in either biometric parameters or anterior chamber configurations. CONCLUSION: While the present findings do not show a significant change in IOP following mydriasis, there was wide inter-individual variation, with some children showing an increase in IOP of up to 8.0 mmHg and some showing a decrease of a similar amount. This variation suggests that IOP should be monitored when mydriatics or cycloplegics are used in children. PMID- 22077325 TI - The sources of error in Brass's method for estimating child survival: the case of Bangladesh. AB - Abstract Brass's method for estimating child mortality is based on an ingeniously simplified model. However, it frequently leads to values of q(x) that are not consistent with each other. This is most obvious for estimates of q(1). This paper examines the extent to which such inconsistencies are caused by simplifications in the model. Three assumptions are relaxed by adjusting for differences in infant mortality by birth order, taking account of annual fluctuations in mortality, and using a different age pattern of fertility for each cohort. These adjustments are applied to data from the 1974 Bangladesh Retrospective Survey of Fertility and Mortality and the 1975 Bangladesh Fertility Survey in which additional data from the Cholera Research Laboratory are used. The resulting estimates are more consistent both internally and with estimates from other surveys and by other procedures. PMID- 22077326 TI - Some remarks on the paper by A. Okore, 'Rural-urban fertility differentials in Southern Nigeria: An assessment of some available evidence'. AB - Abstract In his paper Okore(1) critically examines the view of Olusanya and Ekanem that, partly because of shorter periods of breastfeeding and abstinence associated with 'modernization', urban fertility exceeds rural. Unfortunately, the proponents of this view have produced very few hard data on durations of breast-feeding and abstinence.(2). PMID- 22077327 TI - A rejoinder to David Lucas. AB - Abstract In order to clarify the main points at issue, I shall pinpoint some of the major differences between my approach to the study of fertility differentials in Southern Nigeria and that of Lucas. PMID- 22077330 TI - Interconnected MoO2 nanocrystals with carbon nanocoating as high-capacity anode materials for lithium-ion batteries. AB - A facile one-pot hydrothermal method has been developed for the preparation of carbon-coated MoO(2) nanocrystals. The annealed MoO(2)-C nanocomposite consists of interconnected MoO(2)@C nanocrystals. When evaluated for lithium storage capabilities, these MoO(2)@C nanocrystals exhibit high specific capacities (~640 mA h g(-1) at 200 mA g(-1) and ~575 mA h g(-1) at 400 mA g(-1)) and excellent cycling stability. In view of the excellent lithium storage properties and the ease in large-scale preparation, the as-synthesized MoO(2)-C nanocomposite might be used as promising anode materials for high-performance lithium-ion batteries. PMID- 22077331 TI - Chemical composition and antimicrobial activity of the inflorescence essential oil of Capillipedium parviflorum (R. Br.) Stapf. from India. AB - Essential oil isolated from the inflorescences of Capillipedium parviflorum (R. Br.) Stapf., collected from Kumaon region of Western Himalaya, India, was investigated by GC and GC-MS. A total of 45 constituents representing 99.0% of the essential oil were identified. The major components of this oil were 4 undecanone (33.2%), 4-undecanol (29.7%), 4-nonanol (13.9%), alpha-muurolol (5.3%), 4-tridecanone (3.6%), methyl-2-oxo-nonanoate (3.1%), trans-2-hexenyl butanoate (1.1%) and 1-tetradecanol (1.0%). The antimicrobial activity of the essential oil was determined against eight Gram-positive and Gram-negative bacterial strains, as well as two fungal strains. The bioassay showed that the essential oil possessed good antibacterial activity. PMID- 22077332 TI - Molecular dynamics simulations of low-ordered alzheimer beta-amyloid oligomers from dimer to hexamer on self-assembled monolayers. AB - Accumulation of small soluble oligomers of amyloid-beta (Abeta) in the human brain is thought to play an important pathological role in Alzheimer's disease. The interaction of these Abeta oligomers with cell membrane and other artificial surfaces is important for the understanding of Abeta aggregation and toxicity mechanisms. Here, we present a series of exploratory molecular dynamics (MD) simulations to study the early adsorption and conformational change of Abeta oligomers from dimer to hexamer on three different self-assembled monolayers (SAMs) terminated with CH(3), OH, and COOH groups. Within the time scale of MD simulations, the conformation, orientation, and adsorption of Abeta oligomers on the SAMs is determined by complex interplay among the size of Abeta oligomers, the surface chemistry of the SAMs, and the structure and dynamics of interfacial waters. Energetic analysis of Abeta adsorption on the SAMs reveals that Abeta adsorption on the SAMs is a net outcome of different competitions between dominant hydrophobic Abeta-CH(3)-SAM interactions and weak CH(3)-SAM-water interactions, between dominant electrostatic Abeta-COOH-SAM interactions and strong COOH-SAM-water interactions, and between comparable hydrophobic and electrostatic Abeta-OH-SAM interactions and strong OH-SAM-water interactions. Atomic force microscopy images also confirm that all of three SAMs can induce the adsorption and polymerization of Abeta oligomers. Structural analysis of Abeta oligomers on the SAMs shows a dramatic increase in structural stability and beta sheet content from dimer to trimer, suggesting that Abeta trimer could act as seeds for Abeta polymerization on the SAMs. This work provides atomic-level understanding of Abeta peptides at interface. PMID- 22077333 TI - A concise total synthesis of (+/-)-minfiensine. AB - A concise total synthesis of (+/-)-minfiensine using all conventional methods and starting from commercial materials has been completed. The synthesis features a Fischer indole synthesis, a Heck alkylation of an intermediate ketone enolate, conversion of a ketone carbonyl into an epoxide, and transformation of the latter into an allylic alcohol. PMID- 22077334 TI - Mitophagy: a complex mechanism of mitochondrial removal. AB - SIGNIFICANCE: Mitochondrial dynamics and turnover are crucial for cellular homeostasis and differentiation. The removal of damaged mitochondria that could contribute to cellular dysfunction or death is achieved through the process of mitochondrial autophagy, i.e., mitophagy. Moreover, mitophagy is responsible for removal of mitochondria during terminal differentiation of red blood cells and T cells. RECENT ADVANCES: Recent work is elucidating how mitochondria are recognized for selective mitophagy either by PINK1 and Parkin or mitophagic receptors Nix and Bnip3 and their accompanying modulators. PINK1/Parkin-mediated mitophagy reveals their role of cargo recognition through polyubiquitination of mitochondrial proteins, while Nix functions as a regulated mitophagy receptor. These recognized modes of capture by the autophagy machinery operate at different efficiencies, from partial to complete elimination of mitochondria. CRITICAL ISSUES: It is critical to understand that the distinct regulatory mechanisms involve not only autophagy machinery, but also proteins associated with mitochondrial fusion and fission and therefore, regulation of mitochondrial morphology. The end result is either finely tuned quality control of damaged mitochondria, or mitochondrial clearance during development- induced mitophagy. FUTURE DIRECTIONS: In this article, known mechanisms and future directions for deciphering the challenge of mitophagy regulation will be discussed. PMID- 22077335 TI - Comparative in vitro microdosimetric study of murine- and human-derived cancer cells exposed to alpha particles. AB - Diffusing alpha-emitter radiation therapy (DaRT) is a proposed new form of brachytherapy using alpha particles to treat solid tumors. The method relies on implantable 224Ra-loaded sources that continually release short-lived alpha particle-emitting atoms that spread inside the tumor over a few millimeters. This treatment was demonstrated to have a significant effect on tumor growth in murine and human-derived models, but the degree of tumor response varied across cell lines. Tumor response was found to correlate with the degree of radionuclide spread inside the tumor. In this work we examined the radiosensitivity of individual cells to determine its relationship to tumor response. Cells were irradiated in vitro by alpha particles using a 228Th irradiator, with the mean lethal dose, D0, estimated from survival curves generated by standard methods. The results were further analyzed by microdosimetric tools to calculate z0, the specific energy resulting in a survival probability of 1/e for a single cell, which is considered to better represent the intrinsic radiosensitivity of individual cells. The results of the study demonstrate that, as a rule, tumors that respond more favorably to the DaRT treatment are also characterized by higher intrinsic cellular radiosensitivities, with D0 ranging from 0.7 Gy to 1.5 Gy for the extreme cases and z0 following the same trend. PMID- 22077337 TI - Overexpression of SKP2 promotes the radiation resistance of esophageal squamous cell carcinoma. AB - SKP2 is the substrate recognition subunit of the SCF(SKP2) ubiquitin ligase complex. It is implicated in ubiquitin-mediated degradation of the cyclin dependent kinase (CDK) inhibitor p27(KIP1) and positively regulates the G(1)/S transition. Overexpression of SKP2 has been found in many kinds of tumors. In the present study, we found that SKP2 expression levels increased in esophageal squamous cell carcinoma tissues. Elevated expression of SKP2 correlated significantly with tumor stage and positive lymph node metastasis (P < 0.05). Moreover, a significantly negative correlation was found between SKP2 expression and the survival of patients who received radiotherapy (P < 0.05). At the molecular level, induced expression of SKP2 promoted the radioresistance of EC9706 cells. Knockdown of SKP2 expression sensitized cancer cells to radiation, and a wobble mutant of SKP2 that was resistant to SKP2 siRNA was able to rescue this effect. Increased or decreased expression levels of SKP2 had effects on Rad51 expression after irradiation. These results demonstrate for the first time that overexpression of SKP2 was correlated with the increased radioresistance of esophageal squamous cell carcinoma. Elevated expression of SKP2 promoted the radioresistance of cancer cells, and this effect was mediated at least in part by the Rad51 pathway. PMID- 22077336 TI - Intrachromosomal changes and genomic instability in site-specific microbeam irradiated and bystander human-hamster hybrid cells. AB - Exposure to ionizing radiation may induce a heritable genomic instability phenotype that results in a persisting and enhanced genetic and functional change among the progeny of irradiated cells. Since radiation-induced bystander effects have been demonstrated with a variety of biological end points under both in vitro and in vivo conditions, this raises the question whether cytoplasmic irradiation or the radiation-induced bystander effect can also lead to delayed genomic instability. In the present study, we used the Radiological Research Accelerator Facility charged-particle microbeam for precise nuclear or cytoplasmic irradiation. The progeny of irradiated and the bystander human hamster hybrid (A(L)) cells were analyzed using multicolor banding (mBAND) to examine persistent chromosomal changes. Our results showed that the numbers of metaphase cells involving changes of human chromosome 11 (including rearrangement, deletion and duplication) were significantly higher than that of the control in the progeny of both nuclear and cytoplasmic targeted cells. These chromosomal changes could also be detected among the progeny of bystander cells. mBAND analyses of clonal isolates from nuclear and cytoplasm irradiations as well as the bystander cell group showed that chromosomal unstable clones were generated. Analyses of clonal stability after long-term culture indicated no significant change in the number of unstable clones for the duration of culture in each irradiated group. These results suggest that genomic instability that is manifested after ionizing radiation exposure is not dependent on direct damage to the cell nucleus. PMID- 22077338 TI - Low (20 cGy) doses of 1 GeV/u (56)Fe--particle radiation lead to a persistent reduction in the spatial learning ability of rats. AB - Exposure to galactic cosmic radiation (GCR) is considered to be a potential health risk in long-term space travel, and it represents a significant risk to the central nervous system (CNS). The most harmful component of GCR is the HZE [high-mass, highly charged (Z), high-energy] particles, e.g. (56)Fe. In previous ground-based experiments, exposure to high doses of HZE-particle radiation induced pronounced deficits in hippocampus-dependent learning and memory in rodents. Recent data suggest that glutamatergic transmission in hippocampal synaptosomes is impaired after low (60 cGy) doses of 1 GeV/u (56)Fe particles, which could lead to impairment of hippocampus-dependent spatial memory. To assess the effects of mission-relevant (20-60 cGy) doses of 1 GeV/u (56)Fe particles on hippocampus-dependent spatial memory, male Wistar rats either received sham treatment or were irradiated and tested 3 months later in the Barnes maze test. Compared to the controls, rats that received 20, 40 and 60 cGy 1 GeV/u (56)Fe particles showed significant impairments in their ability to locate the escape box in the Barnes maze, which was manifested by progressively increasing escape latency times over the 3 days of testing. However, this increase was not due to a lack of motivation of the rats to escape, because the total number of head pokes (and especially incorrect head pokes) remained constant over the test period. Given that rats exposed to X rays did not exhibit spatial memory impairments until >10 Gy was delivered, the RBE for 1 GeV/u (56)Fe-particle-induced hippocampal spatial memory impairment is ~50. These data demonstrate that mission relevant doses of 1 GeV/u (56)Fe particles can result in severe deficits in hippocampus-dependent neurocognitive tasks, and the extreme sensitivity of these processes to 1 GeV/u (56)Fe particles must arise due to the perturbation of multiple processes in addition to killing neuronal cells. PMID- 22077339 TI - Ionizing radiation enhances esophageal epithelial cell migration and invasion through a paracrine mechanism involving stromal-derived hepatocyte growth factor. AB - Esophageal cancer is the sixth leading cause of cancer death worldwide and the seventh leading cause of cancer death in the U.S. male population. Ionizing radiation exposure is a risk factor for development of esophageal squamous cell carcinoma, a histological subtype of esophageal cancer that is highly aggressive and is associated with poor patient prognosis. This study investigated the effects of ionizing radiation on the microenvironment and intercellular communication as it relates to esophageal carcinogenesis. We demonstrate that normal esophageal epithelial cells exhibited increased migration and invasion when cultured in the presence of irradiated stromal fibroblasts or with conditioned medium derived from irradiated stromal fibroblasts. Cytokine antibody arrays and ELISAs were used to identify hepatocyte growth factor (HGF) as an abundant protein that is secreted by esophageal fibroblasts at twofold increased levels in culture medium after gamma irradiation. Reverse transcription qPCR analysis confirmed an approximately 50% increase in mRNA levels for HGF at 1 h in irradiated fibroblasts compared to unirradiated controls. Recombinant HGF stimulated increased wound healing, migration and invasion of esophageal epithelial cells, while blocking antibodies against HGF significantly decreased migration and invasion of epithelial cells in coculture with irradiated fibroblasts. Since HGF is known to direct cell migration, invasion and metastasis in a variety of tissues, including the esophagus, its modulation by ionizing radiation may have important implications for nontargeted pathways that influence radiation carcinogenesis in the esophagus. PMID- 22077340 TI - Management of osteonecrosis in children and young adults with acute lymphoblastic leukaemia. AB - Osteonecrosis is a disabling complication in children and young adults with acute lymphoblastic leukaemia. It can affect any or multiple joints but the hip and knee are most frequently involved and a cause of long-term disability. The problem is almost exclusively that of older children and young adults of whom over 70% have asymptomatic changes on screening magnetic resonance imaging and 15 20% have resulting symptoms. Dexamethasone is associated with a higher risk than prednisolone in US but not European or UK trials and alternate week scheduling of dexamethasone in the intensification course is associated with a lower risk than a continuous 3-week schedule in US trials. Genetic factors and obesity contribute to the risk, as do metabolic abnormalities caused by drugs, such as asparaginase, which increase tissue exposure to steroids. Management is primarily supportive but a minority of patients require surgical intervention including replacement of the affected joint. A variety of surgical techniques and, latterly, bisphophonates, have been tried to prevent progression but their efficacy remains uncertain. Whether patients should continue to receive steroids after diagnosis of osteonecrosis is uncertain but most trial investigators recommend stopping them after completion of the intensification phase of treatment. PMID- 22077342 TI - Effect of 10% Sodium Ascorbate and 10% ?-tocopherol in Different Formulations on the Shear Bond Strength of Enamel and Dentin Submitted to a Home-use Bleaching Treatment. AB - Clinical Relevance A significant reduction in bond strength of restorative materials to dentin and enamel after home-use bleaching treatment has been reported. Antioxidizing agents may be a procedure to increase bond strength values. Although no reversal of bond strength values was found for sodium ascorbate, alpha-tocopherol formulated in solution resulted in a significant increase in bond strength of bleached enamel. PMID- 22077341 TI - A patient with cluster headache--due to a brainstem lesion. PMID- 22077343 TI - Sex differences in nicotine dependence among addictions clients accessing a smoking cessation programme in Vancouver, British Columbia, Canada. AB - Most individuals in drug treatment programmes use tobacco and are dependent on nicotine. For 323 participants (65% men, mean age = 49.3 years) with a history of substance use disorder (SUD) and/or psychiatric disorders (PD) enrolled in a tobacco dependence clinic programme, we compared baseline characteristics among women and men and examined factors associated with nicotine dependence (ND). Individuals with mood, anxiety and psychotic disorders were more likely to be female, whereas men were more likely to be characterized by alcohol, cocaine and marijuana use, older age, older age at smoking initiation and higher confidence in quitting smoking scores. In stratified multivariate analyses, among women, history of an anxiety disorder and a greater number of cigarettes smoked per day were associated with higher ND scores; among men, a greater number of cigarettes smoked per day and higher confidence in quitting scores were associated with higher ND scores. Given the differences in smoking, SUD and PD histories between women and men accessing addiction treatment, and differential associations with ND, it is important to further explore factors that may enhance tailored treatments and inform future studies examining biological and psychosocial factors for tobacco use in SUD and PD treatment populations. PMID- 22077344 TI - Systematic review: the treatment of noncardiac chest pain. AB - BACKGROUND: Treatment of noncardiac chest pain (NCCP) remains a challenge. This is in part due to the heterogeneous nature of this disorder. Several conditions are associated with NCCP including gastro-oesophageal reflux disease (GERD), oesophageal dysmotility, oesophageal hypersensitivity as well as others. AIM: To determine the currently available therapeutic modalities for NCCP. METHODS: We performed a systematic review of the literature that was published between January, 1980 and March, 2011. We identified 734 studies; 68 of them met entry criteria. RESULTS: Patients with GERD-related NCCP should receive proton pump inhibitors (PPI) twice daily for at least 8 weeks. Smooth muscle relaxants are only recommended for temporary relief of NCCP with motility disorders. Botulinum toxin injection of the distal oesophagus may be effective in the treatment of NCCP and spastic oesophageal motility disorders. Studies assessing the value of tricyclic antidepressants, trazodone and selective serotonin reuptake inhibitors in NCCP are relatively small, but suggest an oesophageal analgesic effect in NCCP patients that is limited by their side effects profile. The usage of theophylline to treat patients with non-GERD-related NCCP should be weighed against its potential toxicity. Use of complementary medicine has been scarcely studied in NCCP. Patients with coexisting psychological morbidity or those not responding to any medical therapy should be considered for psychological intervention. Cognitive behavioural therapy and hypnotherapy may be useful in the treatment of NCCP. CONCLUSIONS: Patients with GERD-related noncardiac chest pain should be treated with at least double dose PPI. The primary treatment for non-GERD-related noncardiac chest pain, regardless if oesophageal dysmotility is present, is pain modulators. PMID- 22077346 TI - Paradoxes of thermodynamics of swelling equilibria of polymers in liquids and vapors. AB - An automatic registration of the changing size of a single spherical microbead of a cross-linked polymer was applied for studying the swelling process of the bead by the sorption of vapors and/or liquids. Many representatives of all three basic types of polymeric networks, gel-type, hypercrosslinked, and macroporous, were examined. Only the first two display large volume changes and prove suitable for following the kinetics and extent of swelling by the above dilatometric technique. The results unambiguously prove that swelling of all polymeric networks in liquids is always higher than in corresponding saturated vapors (Schroeder's paradox). The general nature of this phenomenon implies that the absolute activity of any sorbate in its liquid form is always larger than in the form of its saturated vapor. Surprisingly, gels with any solvent contents, which fall into the broad range between the vapor-equilibrated and liquid-equilibrated extreme contents, retain their volumes constant in the saturated vapor atmosphere. This paradox of a wide range of gels swollen to a different extent and, nevertheless, standing in equilibrium with saturated vapor is explained by the specificity of the network polymers, namely, that the energy of the solvent polymer interactions is easily compensated by the energy of remaining between chain interactions at any solvent content in the above range. Therefore, the strain-free swollen gels do not generate enhanced vapor pressure, but neither display the ability to take up more sorbate from its vapor. PMID- 22077345 TI - Understanding the relationship between attachment style, pain appraisal and illness behavior in women. AB - Insecure attachment has been hypothesized to be an important factor for understanding the experience of pain. Considering the Attachment-Diathesis Model of Chronic Pain developed by Meredith, Ownsworth, and Strong (2008), this cross sectional study examines the relationship between attachment style, pain appraisal, and illness behavior. Two hundred healthy women recruited from community contexts completed a battery of self-report measures including the Short-form McGill Pain Questionnaire, Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale-20, Pain Vigilance and Awareness Questionnaire, Illness Attitude Scales, Beck Anxiety Inventory, Beck Depression Inventory, and the Experiences in Close Relationships Questionnaire-Revised. The results showed that attachment anxiety was significantly correlated with pain catastrophizing, pain-related fear, depression, and illness behavior. However, attachment anxiety and avoidance were not associated with pain intensity. Attachment anxiety moderated the relationship between pain catastrophizing and illness behavior, and between pain hypervigilance and illness behavior. Pain catastrophizing and pain-related fear partially mediated the effect of attachment anxiety on illness behavior. The findings highlight potential contributions of attachment style and pain appraisal for explaining illness behavior. This study supports earlier reports and suggests the usefulness of assessing attachment style for early identification of people who might exhibit a high risk of dysfunctional responses to pain. Our findings also suggest that increasing people's insight about their attachment style and modifying some associated dysfunctional responses may be important in the treatment of chronic pain. PMID- 22077347 TI - Glycosyl coumarin carbonic anhydrase IX and XII inhibitors strongly attenuate the growth of primary breast tumors. AB - A series of 7-substituted coumarins incorporating various glycosyl moieties were synthesized and investigated for the inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). These coumarins were very weak or ineffective as inhibitors of the housekeeping, off target isoforms CA I and II, but some of them inhibited tumor-associated CA IX and XII in the low nanomolar range. They also significantly inhibited the growth of primary tumors by the highly aggressive 4T1 syngeneic mouse mammary tumor cells at 30 mg/kg, constituting interesting candidates for the development of conceptually novel anticancer drugs. Because CA IX is overexpressed in hypoxic tumors and exhibits very limited expression in normal tissues, such compounds may be useful for treating cancers not responsive to classic chemo- and radiotherapy. PMID- 22077348 TI - Weaning piglets as a model for studying pathophysiology of diarrhea. AB - Abstract During fifty years weaning age of piglets decreased from, in former days, ten to twelve weeks till, nowadays, three to five weeks. Early weaned piglets frequently have diarrhea. When piglets had diarrhea after weaning, enterotoxigenic E. coli (ETEC) or rotavirus were generally detected in the faeces; however, they were also detected in faeces of piglets without diarrhea. So, other causal factors must be involved in the occurrence of diarrhea after weaning. Mortality, due to diarrhea, was associated with severe villus shortening and crypt deepening. Furthermore, weaning piglets was also associated with villus shortening and crypt deepening and giving supplementary feed during the suckling period was effective in preventing villus shortening after weaning. Giving piglets sow's milk immediately after weaning is also effective in preventing villus atrophy. As shown with a small intestine segment perfusion test weaning was also associated with a loss of net absorption in both uninfected and ETEC infected small intestine. The loss of net absorption was less in piglets that were given supplementary feed during the suckling period. Net absorption in the small intestine increased significantly one day after a rotavirus infection and decreased significantly after subsequent infection with ETEC. Function of the large intestine also influences the severity of diarrhea in just weaned piglets. It may be concluded that weaning piglets at an age of three to five weeks changes the flora, the morphology, and the function of the intestine; these changes together result frequently in diarrhea. PMID- 22077349 TI - Correlation between electrophysiological phenomena and transport of macromolecules in intestinal epithelium. AB - Summary This review discuss some recent findings in the study of the regulation of the permeability of the intestinal epithelial layer. Comparison of electrical phenomena and transport of macromolecules suggests that secretory activity and increased transepithelial transport of macromolecules are related when secretion is mediated by the Ca(2+) and PKC dependend pathways. The transport of the macromolecules is via the transcellular and via the paracellular route. The barrier function of the intestinal epithelium may be diminished during nervous (acetylcholine)- and immuno-(histaminc) mediated secretion. It is hypothesised that some bacterial toxins may also induce Ca(2+) and PKC dependent secretion and thereby can reduce the epithelial barrier. The cAMP and cGMP mediated secretion, which can be recognised by their long-lasting transepithelial potential changes, are not coupled to increased transepithelial transport of macromolecules. Some forms of secretory diarrhea may therefore be related to the development of food allergy or inflammation. PMID- 22077350 TI - Food allergy, coeliac disease and chronic inflammatory bowel disease in man. AB - Abstract It is often stated that the gastrointestinal tract has a limited number of responses to pathogens. Entirely different agents can produce a similar histopathological reaction. However, the expression of the disease in man is very heterogeneous, it varies with the age of the subject and is to a certain extent genetically determined. For example, food allergy is frequent in childhood and not common in adulthood. The intestinal mucosa in the child with cows milk allergy shows a 'flat' mucosa, which may be indistinguishable of that observed in gluten sensitive entero-pathy or coeliac disease. Subjects with other forms of food allergy may have a morphologically normal small intestinal mucosa, occasionally with increased IgE plasma cells and often only characterised by an increased intestinal permeability. An abnormal intestinal permeability is one of the hallmarks of an inflamed gut, however, subjects with a latent form of coeliac disease have an abnormal permeability only without overt signs of inflammation. Recently, it has become clear that what determines the characteristics of the intestinal inflammatory response is dependent on the cytokines involved during the response and this seems to be the same in the stomach, the small intestine and the colon. A so-called Th1 response, with an increased production of IFN gamma, TNF-alpha and other pro-inflammatory cytokines, occurs in the stomach when infected by Helicobacter pylori, in the small intestine when the subject with coeliac disease consumes normal bread and during the active phases of Crohn's disease. A Th2 response is characteristic of the allergic subject and there is some evidence that it is the predominant response in subjects with ulcerative colitis. We still do not know the fine-tuning of the cytokine response but IL-12 appears to be a key cytokine in polarising the response to a Thl type. More recently it has become clear that the intestinal mucosa has a unique subset of CD4(+) T cells that secrete TGF-beta (Th3 cells) that provide help for IgA. These cells have downregulatory properties for Th1 cells and therefore play an important role in the active suppression of oral tolerance and IgE response. What determines that an individual develops one of these diseases? It is now clear that these different pathological entities are multifactorial. Different environmental factors and a complex genetic predisposition where more that one gene and more than one chromosome are involved. The extent and severity of the inflammatory response depends on the genetic diversity of the bacteria or the amount of the antigen on the one hand and on the genetic constitution of the host on the other. The abnormal immune response in the human gut is predominantly a Th1-like inflammatory response. This can be elicited by bacteria, peptides, possibly the bacterial flora and some viruses. The recent findings in the pathogenesis of the intestinal inflammatory response will probably alter the therapy of the future. PMID- 22077351 TI - Role of short-chain fatty acids in the hind gut. AB - Abstract Short-chain fatty acids (SCFA) are produced by microbial fermentation in the hindgut in considerable amounts. Most of the anions in hindgut contents are SCFA, mainly acetate, propionate and butyrate. SCFA are rapidly absorbed. Mechanisms involved in the transepithelial transport are discussed. Besides the contribution to the overall energy metabolism of animals or men, SCFA have a number of further important effects on the colonic mucosa. Factors affecting the pH of compartments in the mucosa, cell swelling, stimulation of mucin release and of mucosal blood flow are mentioned. Controversial reports are known on the role of SCFA in the metabolism of colonocytes. In spite of the conflicting opinions on the interaction between SCFA metabolism and the development of colitis ulcerosa, diverticulosis and colorectal cancer seems to exist. The obscure differences between the effects of SCFA on cell proliferation, differentiation and apoptosis of colonocytes in vivo and in vitro indicate that besides direct effects of SCFA systemic effects such as neural and humoral factors are of crucial importance. The opposing effects of SCFA on proliferation and apoptosis in normal colonocytes and in colonic cancer cells may open possibilities for prevention and/or therapy of patients with colonic diseases. PMID- 22077352 TI - Non-starch polysaccharides in pig feeding. AB - Abstract In pigs and humans, the nutrients starch, protein, fat and some minerals need to be digested prior to the terminal ileum for optimal use of these nutrients. In contrast, the non-starch polysaccharides (NSP) are mainly fermented by microbes in the hindgut. Results of experiments in pigs showed that NSP negatively affected apparent digestion of protein, fat and some minerals. In addition, large amounts of fermented NSP increased the empty weight of the hindgut. Because tissue of organs like the intestinal tract are metabolically very active, it may have required more energy for maintenance, hence leaving less energy for growth. Despite all the negative effects as mentioned above, including NSP-rich ingredients in pig diets also has quite a lot of advantages. Their energy supply can cover the energy requirements for maintenance. In addition, positive effects on the well-being and health of pigs, and on the excretion of ammonia are claimed. In conclusion, in future pig diet formulation not only the nutritional aspects of NSP-rich ingredients should be taken into account, but also their non-nutritional aspects. This might be realized by developing nutrient based feed evaluation systems, rather than the energy based systems which are presently used. PMID- 22077353 TI - Weaning piglets, microbial fermentation, short chain fatty acids and diarrhoea. AB - Abstract The effect of weaning on the absorptive capacity of the large intestine (LI) of weaned and unweaned pigs for short chain fatty acids (SCFA), sodium, potassium, and water has been determined by perfusion studies. Ligated loops were formed at four sites in the LI. In both groups the rate of absorption of SCFA, sodium and potassium was increased from the proximal to the distal sites, but this increase was not followed by an increase in the absorption of water. It is concluded that unweaned and weaned pigs can absorb SCFA and electrolytes immediately after weaning, but that a period of adaptation is required for the optimal absorption of water. This lower capacity for the absorption of water in the first two weeks after weaning makes the recently weaned pig vulnerable to a loss of fluid from the intestines. PMID- 22077354 TI - Enteric bacterial pathogens, villus atrophy and microbial growth. AB - Abstract The effects of three bacterial pathogens on the villus architecture of small intestines and the role that bacterial virulence factors play in pathogenesis are described. Bacterial pathogens cause a spectrum of effects ranging from severe tissue damage to a lack of perceptible damage. Enterotoxigenic Escherichia coli, which cause acute and severe diarrhea, does so by producing potent toxins, but these toxins act by altering the biological activity in epithelial cells. However, the cells are not damaged. Enteropathogenic E. coli and Salmonella, on the other hand cause various degrees of tissue damage. As part of their pathogenesis, they employ a type III protein secretion system to orchestrate internal changes in target cells. The expression of many virulence related genes is tightly regulated and appears to be turned on in response to cues found in the intestinal tract. The consequences of this level of regulation also is discussed. PMID- 22077355 TI - Probiotics and E.coli infections in man. AB - Abstract After oral administration of live oral vaccines COLIN-FANT and MUTAFLOR prepared from non-entero-pathogenic E.coli strains, both strains colonized effectively the intestine in full-term and preterm infants and remained for many weeks showing, that they were capable to establish themself as a resident strain in the infant's gut. The presence of E.coli stimulated significantly antibody production in gut, saliva and serum of colonized infants. An early induction of secretory IgA production is important particularly in formula-fed infants, where it partly replaces the lacking immunoglobulin supplied with mother milk. In full-term and premature infants the early presence of non pathogenic E.coli strains in the intestine decreased significantly the presence of pathogenic bacterial strains in the intestine but also other mucosal surfaces of the body. The COLINFANT strain decreased the number of nosocomial infections, mortality rate in connection with infection, and the need for antibiotics. Both strains replaced successfully pathogenic strains in carriers after treatment with antibiotics. PMID- 22077356 TI - Passive and active protection against disorders of the gut. AB - Abstract The large surface area of mucosal surfaces, particularly of the gastrointestinal tract, is protected against microorganisms and environmental antigens by various innate factors (e.g., mucins, lactoferrin, and others) and specific antibodies which are of IgA, or in some species, IgG Isotypes. Passive protection provided by effective prenatal transplacental transport of maternal antibodies and/or post-natal consumption of milk antibodies in breastfed newborns, is essential for the survival of neonates. Passive protection of mucosal surfaces by pre-formed antibodies in non-breast juveniles or adults is currently used only on an experimental basis: IgA-enriched preparations of gamma globulin have been successfully given to children, and antibodies specific for several gastrointestinal pathogens have been isolated from immunized cows' milk, hens' eggs, or transgenic plants. Systemic administration of pre-formed antibodies is effective for protection against intestinal pathogens in species (e.g., mice, rats) endowed with efficient hepato-biliary transport of IgA into the gut lumen. However, this route of antibody administration is of limited efficiency in other species, including humans, in which almost all intestinal antibodies are produced locally by plasma cells in the gut mucosa and are not derived to a significant degree from the circulation. Active immunization is preferable for long-lasting protection. The site of immunization and presence of lymphoid tissues with inductive potential play an essential role in generating humoral immune responses in mucosal secretions. The relative efficiency of immunization routes (e.g., oral, nasal, rectal or genital) in the induction of preferential antibody responses in the intestinal secretion has not been studied extensively. Furthermore, suitable antigen delivery systems for achieving this goal must also be considered. PMID- 22077357 TI - Prevention of diarrhoea using pathogen specific monoclonal antibodies in an experimental enterotoxigenic E. coli infection in germfree piglets. AB - Abstract In the present study we describe the effect of oral application of mAB specific for ETEC F4(ac) fimbriae in an experimental ETEC challenge model in neonatal germfree piglets. The results show that mAB, specific for different F4(ac) epitopes protect animals against ETEC specific pathology. Moreover, the results show that protection is independent of F4(ac) epitope specificity. PMID- 22077359 TI - Carcinogenesis of colorectal cancer. PMID- 22077358 TI - Edible vaccines. AB - Summary The ultimate vaccine is an oral vaccine which given once protects against a multitude of diseases. Furthermore this ultimate vaccine needs to be very stable and inexpensive to produce. Probably this latter condition can be met only if the vaccines are produced in plants. Such vaccines are called 'edible vaccines'. Edible vaccines can be produced in plants in many ways. Using recombinant plant-virus, CPMV, it was shown that plants can produce massive amounts of chimaeric virus particles which protect after a single injection the target animal against disease. The final step, oral adminstration, is being adressed at present. Preliminary experiments by others suggest that this step may be solved sooner than expected. PMID- 22077361 TI - Noncovalent interactions between a trinuclear monofunctional platinum complex and human serum albumin. AB - Interactions between platinum complexes and human serum albumin (HSA) play crucial roles in the metabolism, distribution, and efficacy of platinum-based anticancer drugs. Polynuclear monofunctional platinum(II) complexes represent a new class of anticancer agents that display distinct molecular characters of pharmacological action from those of cisplatin. In this study, the interaction between a trinuclear monofunctional platinum(II) complex, [Pt(3)LCl(3)](ClO(4))(3) (L = N,N,N',N',N",N"-hexakis(2-pyridylmethyl)-1,3,5 tris(aminomethyl)benzene) (1), and HSA was investigated using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, circular dichroism spectroscopy, fluorescence spectroscopy, molecular docking, and inductively coupled plasma mass spectrometry. The spectroscopic and thermodynamic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being 14.6 kJ mol(-1) and 145.5 J mol(-1) K(-1), respectively. The reactive sites of HSA to complex 1 mainly locate within its hydrophobic cavity in domain II. Noncovalent actions such as pi-pi stacking and hydrophobic bonding are the primary contributors to the interaction between HSA and complex 1, which is different from the scenario for cisplatin in similar conditions. The results suggest that the connection between complex 1 and HSA is reversible, and therefore the cytotoxic activity of the complex could be preserved during blood circulation. PMID- 22077362 TI - Sebaceous hyperplasia within epidermis after scald. AB - A 16-year-old girl with polycystic ovarian syndrome presented with numerous rufous papules arising within a large depigmented macule that developed following a severe scald injury on the back. Histopathology revealed that many mature sebaceous glands were growing in the middle and bottom of the epidermis with slight acanthosis. On the basis of patient history, clinical manifestation and histopathology, we suggested that this patient's skin lesion be diagnosed as 'sebaceous hyperplasia within epidermis after scald'. PMID- 22077363 TI - Molecular mechanisms underlying effects of neural stem cells against traumatic axonal injury. AB - Transplantation of neural stem cells (NSCs) improves functional outcomes following traumatic brain injury (TBI). Previously we demonstrated that human NSCs (hNSCs) via releasing glial cell line-derived neurotrophic factor (GDNF), preserved cognitive function in rats following parasagittal fluid percussion. However, the underlying mechanisms remain elusive. In this study, we report that NSC grafts significantly reduce TBI-induced axonal injury in the fimbria and other brain regions by blocking abnormal accumulation of amyloid precursor protein (APP). A preliminary mass spectrometry proteomics study revealed the opposite effects of TBI and NSCs on many of the cytoskeletal proteins in the CA3 region of the hippocampus, including alpha-smooth muscle actin (alpha-SMA), the main stress fiber component. Further, Western blot and immunostaining studies confirmed that TBI significantly increased the expression of alpha-SMA in hippocampal neurons, whereas NSC grafts counteracted the effect of TBI. In an in vitro model, rapid stretch injury significantly shortened lengths of axons and dendrites, increased the expression of both APP and alpha-SMA, and induced actin aggregation, effects offset by GDNF treatment. These GDNF protective effects were reversed by a GDNF-neutralizing antibody or a specific calcineurin inhibitor, and were mimicked by a specific Rho inhibitor. In summary, we demonstrate for the first time that hNSC grafts and treatment with GDNF acutely reduce traumatic axonal injury and promote neurite outgrowth. Possible mechanisms underlying GDNF mediated neurite protection include balancing the activity of calcineurin, whereas GDNF-induced neurite outgrowth may result from the reduction of the abnormal alpha-SMA expression and actin aggregation via blocking Rho signals. Our study also suggests the necessity of further exploring the roles of alpha-SMA in the central nervous system (CNS), which may lead to a new avenue to facilitate recovery after TBI and other injuries. PMID- 22077364 TI - The effect of normothermic recirculation before cold preservation on post transplant injury of ischemically damaged donor kidneys. AB - Kidneys recovered from donation after cardiac death (DCD) are increasingly used to enlarge the deceased donor pool. Such renal grafts, especially those derived from uncontrolled DCD, have inevitably sustained profound warm ischemic injury, which compromises post-transplant function. Normothermic recirculation (NR) of the deceased donor's body before organ cooling could be an interesting approach to mitigate the detrimental effect of warm ischemia. To date, however, there is no evidence coming from preclinical studies to support the principle of NR in kidney transplantation. In this study, we subjected 48 Lewis rat kidneys to 15 or 30 min of warm ischemia, and subsequently 0, 1, or 2 h of NR. After 24 h cold storage, kidneys were transplanted into a recipient animal and 24 h later we measured the percentage of cortical necrosis, and determined gene expression of heme oxigenase-1, heat shock protein-70, transforming growth factor-beta, kidney injury molecule-1, interleukin-6, hypoxia inducible factor-1alpha, monocyte chemoattractant protein-1, and alpha-smooth muscle actin in kidney tissue. We found that NR had no significant influence on any of these markers. Therefore, we conclude that this animal study by no means supports the presumed beneficial effect of NR on kidneys that have been severely damaged by warm ischemia. PMID- 22077365 TI - Drug eruption with eosinophilia and systemic syndrome associated with reactivation of human herpesvirus 7, not human herpesvirus 6. PMID- 22077366 TI - The present value of population growth in the western world. AB - Abstract In conventional steady-state growth theory with technical progress exogenous, faster population growth causes lower consumption. This conclusion has influenced national policies. With technical progress endogenous, however, higher population growth causes higher consumption. Steady-state equilibrium analysis is not appropriate for policy decisions, though. Rather, appropriate analysis compares two or more growth rates beginning from equal initial positions, with comparison of the present value of consumption streams per person. In the paper the supply of and demand for knowledge is first analysed and the most plausible technical progress functions are derived. Various population growth rates are then simulated with different specifications and parameters. With virtually every variant, faster population growth shows better consumption with discount rates up to between five and ten per cent above the long-run adjusted riskless rate. With pensions included in the analysis, faster population growth would seem even more beneficial. Even at very high discount rates, lower population growth rates imply present values only a little higher than those for higher population growth rates. The advantage is overwhelmingly with higher population growth in this growth-theoretic analysis. PMID- 22077367 TI - Population dynamics based on birth intervals and parity progression. AB - Abstract The Chinese population policy of 'later-longer-fewer' suggests a formulation of population dynamics in terms of birth intervals and parity progression. This leads to population projections based on birth interval distributions and parity progression ratios and to an alternative to Lotka's stable population theory in which age is replaced by parity and interval since last birth. A numerical comparison with Lotka's model indicates similarities and differences between the two approaches: The formulation suggests an approach to the analysis of birth interval and parity progression statistics that effectively solves censoring and selection problems. PMID- 22077368 TI - A census-based method for estimating adult mortality. AB - Abstract A simple method is presented for converting an age distribution in any closed population into the stationary population corresponding to its current mortality conditions. The conversion only requires a set of age-specific growth rates, which will normally be available from successive censuses. From the stationary population, any life table mortality measure of interest can be computed. The index most robust to normal data errors in developing countries is life expectancy, and the paper focuses on its calculation. The sensitivity of results to various forms of data error is considered, and procedures are proposed for removing errors resulting from differential census coverage completeness and from age misstatement at older ages. Applications of the procedures are made to data from Sweden, India and South Korea. Because of the absence of a radix, estimation of life expectancy usually will begin at the fifth birthday. PMID- 22077369 TI - A reducible four-parameter system of model life tables. AB - Abstract In this paper a four-parameter extension of Brass's relational system of model life tables is suggested that (1) matches a wide range of empirical age patterns of mortality, (2) is easy to apply, especially to partial life tables, and (3) contains demographically meaningful parameters. A test of the model on a set of 62 empirical life tables indicates that four parameters are necessary and sufficient for fitting a wide range of mortality patterns. A further test on an historical series of Swedish life tables reveals a consistent pattern of mortality change. Examination of the parameters for a set of geographicallyrelated life tables suggests a way to define families of life tables. Identification of such temporal and spatial relationships allows the model to be reduced to a form with twoor three-parameters for application to incomplete or inaccurate data. PMID- 22077370 TI - The use of traditional and modern methods of fertility control in Kinshasa, Zaire. AB - Abstract The practice of post-partum abstinence has been a long-standing tradition in many societies of tropical Africa, yet recent research suggests an erosion of the taboo on post-partum sexual relations as a means of fertility control. The current study among women in the lower income groups in Kinshasa, Zaire, provides evidence of this. There is strong motivation toward child spacing, as shown by 80 per cent of the women who reported to be currently practising some means of fertility control: 73 per cent with traditional methods, only 7 per cent with modern contraceptives. There appears to be some carry-over of traditional practice, in that abstinence is related to the age and nursing status of the last born child. However, the most widely practised method is withdrawal. This suggests a desire on the part of this population for alternatives to abstinence, an issue with important implications for future family planning programs in Zaire. PMID- 22077373 TI - Comparison of simple Eudragit microparticles loaded with prednisolone and Eudragit-coated chitosan-succinyl-prednisolone conjugate microparticles: Part I. Particle characteristics and in vitro evaluation as a colonic delivery system. AB - OBJECTIVE: Simple Eudragit microparticles loaded with prednisolone and chitosan succinyl-prednisolone conjugate microparticles coated with Eudragit were prepared and characterized in vitro in order to obtain their basic features as a colonic delivery system. MATERIALS AND METHODS: Both types of microparticles were prepared by the emulsification-solvent evaporation modified somewhat from the previous one. Their particle size, shape and their drug content were investigated, and in vitro release profiles were examined using JP-15 1st fluid (pH 1.2), JP-15 2nd fluid (pH 6.8) and PBS (pH 7.4) as release media. Furthermore, the regeneration of conjugate microparticles from Eudragit-coated microparticles was investigated under the same incubation conditions. RESULTS: Simple Eudragit S100 (EuS) microparticles (ES-M) were almost spherical, ca. 1.2 MUm diameter, and PD content ca. 3.7% (w/w). Conjugate microparticles (CS-M1) and EuS-coated conjugate microparticles (CS-M1/S) had particle sizes of ca. 2.8 and 15.3 MUm, respectively, and PD contents of 5.4 and 2.1% (w/w), respectively. ES-M exhibited suppressed release at pH 1.2, gradual release at pH 6.8 and rapid release at pH 7.4. CS-M1 showed no release at pH 1.2, and very slow release at pH 6.8 and 7.4. CS-M1 regenerated poorly from CS-M1/S at pH 6.8. CONCLUSIONS: Simple Eudragit micrparticles and Eudragit-caoted conjugate microparticles, prepared by the present methods, were found in vitro to be possibly useful as the delivery systems of PD to the lower intestine, although there were differences in their release rate and morphological features. PMID- 22077374 TI - Healthcare burden associated with the post-thrombotic syndrome and potential impact of the new oral anticoagulants. AB - Deep-vein thrombosis (DVT) can have a significant impact on a patient's life. In particular, the development of post-thrombotic syndrome as a long-term complication of DVT can have devastating consequences for the individual and impose a substantial economic burden on healthcare systems. Anticoagulants are the mainstay of DVT treatment; however, the current standard of care, a parenteral anticoagulant followed by a vitamin K antagonist, is associated with complex patient management, often resulting in suboptimal therapy. New, oral anticoagulants have been developed, and a direct thrombin inhibitor--dabigatran etexilate--and two direct Factor Xa inhibitors--rivaroxaban and apixaban--have completed and/or have ongoing phase III trials in the treatment of venous thromboembolism. These agents do not have the drawbacks of the vitamin K antagonists and hold promise for more effective treatment of DVT, possibly resulting in a reduction in the incidence of post-thrombotic syndrome. PMID- 22077375 TI - Properties of an Earth-like planet orbiting a Sun-like star: Earth observed by the EPOXI mission. AB - NASA's EPOXI mission observed the disc-integrated Earth and Moon to test techniques for reconnoitering extrasolar terrestrial planets, using the Deep Impact flyby spacecraft to observe Earth at the beginning and end of Northern Hemisphere spring, 2008, from a range of ~1/6 to 1/3 AU. These observations furnish high-precision and high-cadence empirical photometry and spectroscopy of Earth, suitable as "ground truth" for numerically simulating realistic observational scenarios for an Earth-like exoplanet with finite signal-to-noise ratio. Earth was observed at near-equatorial sub-spacecraft latitude on 18-19 March, 28-29 May, and 4-5 June (UT), in the range of 372-4540 nm wavelength with low visible resolving power (lambda/Deltalambda=5-13) and moderate IR resolving power (lambda/Deltalambda=215-730). Spectrophotometry in seven filters yields light curves at ~372-948 nm filter-averaged wavelength, modulated by Earth's rotation with peak-to-peak amplitude of <=20%. The spatially resolved Sun glint is a minor contributor to disc-integrated reflectance. Spectroscopy at 1100-4540 nm reveals gaseous water and carbon dioxide, with minor features of molecular oxygen, methane, and nitrous oxide. One-day changes in global cloud cover resulted in differences between the light curve beginning and end of <=5%. The light curve of a lunar transit of Earth on 29 May is color-dependent due to the Moon's red spectrum partially occulting Earth's relatively blue spectrum. The "vegetation red edge" spectral contrast observed between two long-wavelength visible/near-IR bands is ambiguous, not clearly distinguishing between the verdant Earth diluted by cloud cover versus the desolate mineral regolith of the Moon. Spectrophotometry in at least one other comparison band at short wavelength is required to distinguish between Earth-like and Moon-like surfaces in reconnaissance observations. However, measurements at 850 nm alone, the high reflectance side of the red edge, could be sufficient to establish periodicity in the light curve and deduce Earth's diurnal period and the existence of fixed surface units. PMID- 22077376 TI - Pregnancy in type 2B VWD: a case series. AB - Type 2B von Willebrand disease (VWD) is a rare, inherited bleeding disorder resulting from a qualitative defect in von Willebrand factor (VWF). There is very little published information on how to quantify bleeding risk and manage haemostasis in type 2B VWD patients during pregnancy. This article presents the changes in VWF parameters and details of patient management and delivery outcomes for four pregnancies in three women with two different mutations causing type 2B VWD. We report an unexpected rise in the VWF:Ag at 37 weeks gestation in two sisters with R1306W associated with significant thrombocytopenia. These patients were supported with platelet transfusions as well as intermediate purity VWF FVIII plasma concentrates during the peri- and postpartum periods. No thrombocytopenia was observed in our third case with a mutation encoding an R1308C substitution; haemostatic support was with intermediate purity VWF-FVIII plasma concentrates alone. No adverse bleeding events occurred and in all cases a live healthy infant was delivered. One patient was readmitted post partum with bleeding symptoms due to retained placenta; no further haemostatic support was given at this time. This case series is the first to detail the progression of laboratory parameters, management and outcomes of pregnancy in patients with type 2B VWD. The cases illustrate some of the challenges posed by the increased production of a VWF variant with a gain-of-function effect. The rapid coagulation changes observed in this series illustrate the need for continual monitoring of VWF parameters and platelet count throughout pregnancy in women with type 2B VWD. PMID- 22077377 TI - Charge, stereochemistry, or epitaxy? Toward controlled biomimetic nucleation at mixed monolayer templates. AB - Floating monolayer mixtures of cationic dioctadecyldimethyldiammonium bromide and anionic lipids were used as variable templates for the biomimetic nucleation of calcium carbonate and studied using grazing incidence X-ray diffraction. Varying the ratio of constituents changes the monolayer charge, structure, and molecular tilt. The nucleating surface of calcite also changes as the mixture is varied, and at an 80:20 ratio the (012) face is seen under a floating monolayer template for the first time. Our results indicate that the average template lattice is the major controlling factor in the oriented nucleation of CaCO(3). This is in contrast to the current view that the orientation is controlled by the stereochemical matching of the terminal functional group and molecular tilt with respect to the carbonate groups in the crystal. PMID- 22077378 TI - A polydimethylsiloxane (PDMS) sponge for the selective absorption of oil from water. AB - We present a sugar-templated polydimethylsiloxane (PDMS) sponge for the selective absorption of oil from water. The process for fabricating the PDMS sponge does not require any intricate synthesis processes or equipment and it is not environmentally hazardous, thus promoting potential in environmental applications. The proposed PDMS sponge can be elastically deformed into any shape, and it can be compressed repeatedly in air or liquids without collapsing. Therefore, absorbed oils and organic solvents can be readily removed and reused by simply squeezing the PDMS sponge, enabling excellent recyclability. Furthermore, through appropriately combining various sugar particles, the absorption capacity of the PDMS sponge is favorably optimized. PMID- 22077379 TI - Ruthenium-catalyzed C-H/N-O bond functionalization: green isoquinolone syntheses in water. AB - Ruthenium-catalyzed isoquinolone syntheses with ample scope were accomplished through carboxylate assistance in environmentally benign water as a reaction medium. The high chemoselectivity of the ruthenium(II) carboxylate complex also set the stage for the direct use of free hydroxamic acids for annulations of alkynes. PMID- 22077381 TI - (18)F-FDG PET/CT may be useful when evaluating a patient for giant cell arteritis. PMID- 22077382 TI - A new phenylalkanoid from the rhizomes of Zingiber officinale. AB - A new phenylalkanoid, (E)-3-hydroxy-1-(4'-dihydroxy-3',5'-dimethoxy-phenyl) dodecan-6-en-5-one (1) was isolated from the rhizomes of Chinese ginger (Zingiber officinale Roscoe (Zingiberaceae)). The structure of this new phenylalkanoid was elucidated by chemical and physical evidences. PMID- 22077380 TI - CCR5 blockade is well tolerated and induces changes in the tissue distribution of CCR5+ and CD25+ T cells in healthy, SIV-uninfected rhesus macaques. AB - BACKGROUND: CCR5 is a main co-receptor for HIV, but also homes lymphocytes to sites of inflammation. We hypothesized that inhibition of CCR5 signaling would reduce HIV-associated chronic immune activation. METHODS: To test this hypothesis, we administered an antagonistic anti-CCR5 monoclonal antibody (HGS101) to five uninfected rhesus macaques (RMs) and monitored lymphocyte dynamics in blood and tissue. RESULTS: CCR5 blockade resulted in decreased levels of CCR5+ T cells in blood and, at later timepoints, in lymph nodes. Additionally, the levels of CD25+ T cells increased in lymph nodes, but decreased in blood, bone marrow, and rectal mucosa. Finally, a profile of gene expression from HGS101 treated RMs revealed a subtle, but consistent, in vivo signature of CCR5 blockade that suggests a mild immune-modulatory effect. CONCLUSIONS: Treatment with anti CCR5 antibody induces changes in the tissue distribution of CCR5+ and CD25+ T cells that may impact on the overall levels of immune activation during HIV and SIV infection. PMID- 22077383 TI - Development of a measurement and feedback training tool for the arm strokes of high-performance luge athletes. AB - Previous studies have shown that the start plays a critical role in sliding events and explains more than 55% of the variance of the final time in luge. Experts evaluate the contribution of the arm strokes to be 23% of the total starting performance. The aim of the present study was to develop a measurement and feedback training tool (Speedpaddler) for the arm strokes of high-performance luge athletes. The construction is an aluminium alloy framework with a customary belt conveyor system, which is driven by two synchronized servo motors. Training is possible with constant speeds up to 12 m . s(-1) or several speed curves, which simulate the acceleration of different luge tracks. The construction facilitates variations in the inclination and speed of the conveyor belts and thereby the resistance and movement speed. If the athlete accelerates the conveyor belts during arm-paddling, the torque of the motors decreases. Torque measurements and high-speed video offer valuable insights into the several technique criteria. Comparisons of arm-paddle cycle durations on ice and on the Speedpaddler with 18 luge athletes (national team and juniors) showed no statistical differences. The Speedpaddler might be a useful tool to improve starting performance all year round. PMID- 22077384 TI - How hydrogen bonds influence the mobility of imidazolium-based ionic liquids. A combined theoretical and experimental study of 1-n-butyl-3-methylimidazolium bromide. AB - The virtual laboratory allows for computer experiments that are not accessible via real experiments. In this work, three previously obtained charge sets were employed to study the influence of hydrogen bonding on imidazolium-based ionic liquids in molecular dynamics simulations. One set provides diffusion coefficients in agreement with the experiment and is therefore a good model for real-world systems. Comparison with the other sets indicates hydrogen bonding to influence structure and dynamics differently. Furthermore, in one case the total charge was increased and in another decreased by 0.1 e. Both the most acidic proton as well as the corresponding carbon atom were artificially set to zero, sequentially and simultaneously. In the final setup a negative charge was placed on the proton in order to introduce a barrier for the anion to contact the cation via this most acidic hydrogen atom. The following observations were made: changing the hydrogen bonding ability strongly influences the structure while the dynamic properties, such as diffusion and viscosity, are only weakly changed. However, the introduction of larger alterations (stronger hydrogen bonding and antihydrogen bonding) also strongly influences the diffusion coefficients. The dynamics of the hydrogen bond, ion pairing, and the ion cage are all affected by the level of hydrogen bonding. A change in total charges predominantly influences transport properties rather than structure. For ion cage dynamics with respect to transport porperties, we find a good correlation and a weak or no correlation for the ion pair or the hydrogen bond dynamics, respectively. Nevertheless, the hydrogen bond does influence ion cage dynamics. Therefore, we confirm that ionic liquids rather consist of loosely interacting counterions than of discrete ion pairs. Hydrogen bonding affects the properties only in a secondary or indirect manner. PMID- 22077386 TI - Conical intersection of the ground and first excited states of water: energies and reduced density matrices from the anti-Hermitian contracted Schrodinger equation. AB - A conical intersection between the ground and first-excited states of water is computed through the direct calculation of two-electron reduced density matrices (2-RDMs) from solutions of the anti-Hermitian contracted Schrodinger equation (ACSE). This study is an extension of a previous study in which the ACSE was used to compute the energies around a conical intersection in the triplet excited states of methylene [Snyder, J. W., Jr.; Rothman, A. E.; Foley, J. J.; Mazziotti, D. A. J. Chem. Phys. 2010, 132, 154109]. We compute absolute energies of the 1(1)A' and 2(1)A' states of water (H(2)O) and the location of the conical intersection. The ACSE energies are compared to those from ab initio wave function methods. To treat multireference correlation, we seed the ACSE with an initial 2-RDM from a multiconfiguration self-consistent field (MCSCF) calculation. Unlike the situation for methylene, the two states in the vicinity of the conical intersection of water both have the same spatial symmetry. Hence, the study demonstrates the ability of the ACSE to resolve states of the same spatial symmetry that are nearly degenerate in energy. The 2-RDMs from the ACSE nearly satisfy necessary N-representability conditions. Comparison of the results from double-zeta and augmented double-zeta basis sets demonstrates the importance of augmented (or diffuse) functions for determining the location of the conical intersection. PMID- 22077385 TI - Hybrid schwannoma/perineurioma: a report of two cases including a possible radiation-induced case. AB - Hybrid schwannoma/perineurioma represents a recently characterized dermal or subdermal tumor showing schwannian cytomorphology and a perineurioma-like architecture composed of an admixture of both cell types. We report two additional cases of hybrid schwannoma/ perineurioma, one of which occurred after irradiation. Patient 1 was that of a 33-year-old man presented with a 2.8-cm dermal tumor on his left lower leg. Patient 2 was that of an 89-year-old woman with a history of uterine carcinoma treated by surgery and radiation therapy at the age of 35. She presented with a 1.2 * 1.0 cm dermal tumor on her left mons pubis with multiple coincidental basal-cell carcinomas around it. Both tumors were microscopically well circumscribed but unencapsulated and situated in the dermis and adipose tissue and showed a vague storiform and lamellar pattern. Cytologically, both tumors contained two-cell populations, i.e. spindled cells with plump nuclei, which were positive for S-100 protein and negative for epithelial membrane antigen (EMA), claudin-1 and CD34, as well as cells with very slender nuclei and elongated cytoplasmic processes, which were negative for S-100 protein yet expressed EMA, claudin-1 and CD34. Claudin-1 was a better marker to highlight cells with very slender nuclei than EMA. Both tumors lacked expression of neurofilament. PMID- 22077387 TI - Galactose-decorated pH-responsive nanogels for hepatoma-targeted delivery of oridonin. AB - Nanogels based on the polymers of galactosylated chitosan-graft-poly (N isopropylacrylamide) (Gal-CS-g-PNIPAm) were used as carriers of oridonin (ORI) for tumor targeting. Three ORI-loaded nanogels with various degrees of galactose substitution were prepared, and their characteristics were evaluated. The release behavior of ORI from these nanogels was pH-dependent, and the release could be accelerated under mildly acidic conditions. The cytotoxicity of ORI-loaded nanogels was pH-sensitive. ORI-loaded nanogels exhibited a higher antitumor activity than drug-loaded nanogels without galactosylation, and the anticancer activity increased in relation to increases in the number of galactose moieties of the nanogels in HepG2 cells. In contrast, the cytotoxicity of ORI-loaded nanogels against MCF-7 cells decreased compared with that of drug-loaded nanogels without galactosylation. Results demonstrated that these nanogels could enhance the uptake of ORI into HepG2 cells via asialoglycoprotein receptor-mediated endocytosis. These galactose-decorated pH-responsive nanogels were well-suited for targeted drug delivery to liver cancer cells. PMID- 22077388 TI - Interactions between killer immunoglobulin-like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm. AB - In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin-like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft-versus-host disease (GvHD) [hazard risk (HR) 4.2, 95% confidence interval (CI) 1.7-10.1, P = 0.002] and transplantation-related mortality (HR 4.7, 95% CI 1.6-14.2, P = 0.01). The risk of GvHD furthermore increased when recipients heterozygous for HLA-C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6.1, 95% CI 1.9-19.2, P = 0.002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA-KIR ligand group and the donor carried two or more activating KIRs (HR 6.8, 95% CI 1.9-24.4, P = 0.005). By interpolating the number of donor activating KIRs with recipient HLA-C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision-making. PMID- 22077389 TI - Privileged scaffolds or promiscuous binders: a comparative study on rhodanines and related heterocycles in medicinal chemistry. AB - Rhodanines and related five-membered heterocycles with multiple heteroatoms have recently gained a reputation of being unselective compounds that appear as "frequent hitters" in screening campaigns and therefore have little value in drug discovery. However, this judgment appears to be based mostly on anecdotal evidence. Having identified various rhodanines and related compounds in screening campaigns, we decided to perform a systematic study on their promiscuity. An amount of 163 rhodanines, hydantoins, thiohydantoins, and thiazolidinediones were synthesized and tested against several targets. The compounds were also characterized with respect to aggregation and electrophilic reactivity, and the binding modes of rhodanines and related compounds in published X-ray cocrystal structures were analyzed. The results indicate that the exocyclic, double bonded sulfur atom in rhodanines and thiohydantoins, in addition to other structural features, offers a particularly high density of interaction sites for polar interactions and hydrogen bonds. This causes a promiscuous behavior at concentrations in the "screening range" but should not be regarded as a general knockout criterion that excludes such screening hits from further development. It is suggested that special criteria for target affinity and selectivity are applied to these classes of compounds and that their exceptional and potentially valuable biomolecular binding properties are consequently exploited in a useful way. PMID- 22077391 TI - Communication. PMID- 22077390 TI - Low prevalence of inhibitor antibodies in the Canadian haemophilia population. AB - Annual reporting of inhibitors to factors (FVIII) and IX (FIX) to the Canadian Haemophilia Registry has suggested a lower prevalence than that published in the literature. We performed a prospective study to determine the prevalence of patients with inhibitors directed against either FVIII or FIX. Patients with inhibitors were classified as: (i) inhibitor test positive; (ii) inhibitor test negative but on immune tolerance induction (ITI); (iii) inhibitor test negative but bypass treatment recommended; or (iv) inhibitor resolved. One year later, the cohort was re-classified. The prevalence of inhibitors on 1 May, 2007 was 3.3% for haemophilia A, 0.6% for haemophilia B and 8.9% and 2.1% for severe haemophilia A and B. One year later 17 individuals gained and 11 individuals lost inhibitor status (10 of these with ITI). This study suggests that the prevalence of inhibitors in our population is lower than that was previously published. We hypothesize that this is primarily due to the increased use of ITI, but other factors may be the unselected nature of the cohort and the restriction of the study to one date thereby conforming as close as practical to the definition of prevalence rather than incidence. The classification system used in this study was easy for clinics to apply and was important in defining the population with inhibitors. PMID- 22077392 TI - Structure characterisation of a alpha beta-glucan polysaccharide from Auricularia polytricha. AB - A water-soluble alpha beta-glucan with a molecular weight of 1.62 * 10(5) Da, AAPS -1, was obtained from the fruiting bodies of the edible mushroom Auricularia polytricha by a combined separation of high-speed countercurrent chromatography (HSCCC)-Sephacryl S-300 HR column chromatography. The structure of AAPS-1 was elucidated that the polysaccharide possesses a backbone composed of (1 -> 6) linked-alpha-D-glucopyranosyl and (1 -> 6)-linked-beta-D-glucopyranosyl residues, partially substituted at O-3 of beta-D-glucopyranosyl residue by side chain (1 -> 4)-alpha-D-Glcp and terminated with non-reducing end alpha-D-Glcp-(1 -> on the basis of the analyses of partial hydrolysis, periodate oxidation, acetylation, methylation and NMR spectroscopy ((1)H, (13)C). PMID- 22077393 TI - Crystal structure and magnetic properties of two new antiferromagnetic spin dimer compounds; FeTe3O7X (X = Cl, Br). AB - Two new isostructural layered oxohalides FeTe(3)O(7)X (X = Cl, Br) were synthesized by chemical vapor transport reactions, and their crystal structures and magnetic properties were characterized by single-crystal X-ray diffraction, Raman spectroscopy, magnetic susceptibility and magnetization measurements, and also by density functional theory (DFT) calculations of the electronic structure and the spin exchange parameters. FeTe(3)O(7)X crystallizes in the monoclinic space group P2(1)/c with the unit cell parameters a = 10.7938(5), b = 7.3586(4), c = 10.8714(6) A, beta = 111.041(5) degrees , Z = 4 for FeTe(3)O(7)Cl, and a = 11.0339(10), b = 7.3643(10), c = 10.8892(10) A, beta = 109.598(10) degrees , Z = 4 for FeTe(3)O(7)Br. Each compound has one unique Fe(3+) ion coordinating a distorted [FeO(5)] trigonal bipyramid. Two such groups share edges to form [Fe(2)O(8)] dimers that are isolated from each other by Te(4+) ions. The high temperature magnetic properties of the compounds as well as spectroscopic investigations are consistent with an isolated antiferromagnetic spin dimer model with almost similar spin gaps of ~35 K for X = Cl and Br, respectively. However, deviations at low temperatures in the magnetic susceptibility and the magnetization data indicate that the dimers couple via an interdimer coupling. This interpretation is also supported by DFT calculations which indicate an interdimer exchange which amounts to 25% and 10% of the intradimer exchange for X = Cl and Br, respectively. The magnetic properties support the counterion character and a weak integration of halide ions into the covalent network similar to that in many other oxohalides. PMID- 22077395 TI - Prurigo pigmentosa treated with Jessner's peel and irradiation with an 830-nm light-emitting diode. PMID- 22077394 TI - Short-duration treatment with the calpain inhibitor MDL-28170 does not protect axonal transport in an in vivo model of traumatic axonal injury. AB - Traumatic axonal injury is characterized by early cytoskeletal proteolysis and disruption of axonal transport. Calpain inhibition has been shown to protect axons in rodent models of traumatic brain injury. However, in these models, both white and gray matter are injured, making it difficult to determine if calpain inhibitors are directly protecting injured axons. To address this issue, we used our rat optic nerve stretch model to test the hypothesis that early calpain inhibition directly protects central nervous system (CNS) axons following stretch injury. Rats were given an intravenous bolus of the calpain inhibitor MDL-28170 (30 mg/kg) 30 min prior to unilateral optic nerve stretch, followed by a 15 mg/kg/h intravenous infusion over the next 2.5 h. Immunohistochemical analysis of optic nerves 30 min after stretch injury revealed variable increases of calpain cleaved alpha-spectrin that appeared less evident in stretched nerves from drug treated rats, although this difference was not statistically significant. Retrograde axonal transport measured by Fluorogold(r) labeling of retinal ganglion cells was significantly impaired after stretch injury. However, there was no difference in the number of Fluorogold-labeled cells in the vehicle vs. drug treatment groups. These results suggest that early short-duration calpain inhibitor therapy with MDL-28170 is not an effective strategy to prevent disruption of axonal transport following isolated axonal stretch injury in the CNS. PMID- 22077396 TI - Altered redox homeostasis in human diabetes saliva. AB - BACKGROUND: Oxidative stress has been implicated in the pathogenesis of diabetes mellitus (DM). Levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi prostaglandin-F(2alpha) (8-epi-PGF2alpha), and total protein carbonyls were measured to assess whether DM is associated with altered salivary redox homeostasis. METHODS: A total of 215 patients with diabetes and 481 healthy controls were recruited from the Department of Endocrinology at the Jewish General Hospital in Montreal. Levels of oxidative biomarkers were assayed using enzyme-linked immunosorbent assay (ELISA) in whole unstimulated saliva. Associations of the redox data with exposure to insulin, metformin and dietary control were assessed by logistic regression analyses. RESULTS: We observed (i) significantly higher mean levels of 8-OHdG and protein carbonyls in whole unstimulated saliva of patients with diabetes compared to controls, (ii) higher mean levels of protein carbonyls in type 1 diabetes as well as higher mean levels of 8-OHdG and protein carbonyls in type 2 diabetes compared to controls, (iii) elevated levels of protein carbonyls in diet-controlled patients and in patients with diabetes on insulin and metformin, (iv) elevated levels of 8-OHdG in patients on metformin, and (v) significant associations between subjects with DM and salivary 8-OHdG and protein carbonyls. CONCLUSION: DM is associated with increased oxidative modification of salivary DNA and proteins. Salivary redox homeostasis is perturbed in DM and may inform on the presence of the disease and efficacy of therapeutic interventions. PMID- 22077397 TI - Induction of caspase-2 activation by a DNA enzyme evokes tumor cell apoptosis. AB - Caspase-2 is an enigmatic caspase that is now increasingly being associated with certain types of cell death in cells exposed to cytotoxic agents. It is now known that in some cases of cell stress, such as DNA damage, activation of this caspase is triggered, sometimes in the absence of activation of both the intrinsic and extrinsic pathways of apoptosis. Part of the reason for this enigma has been lack of a suitable stimulus for this caspase, and with the discovery of DNAzyme 13 (Dz13), a potent oligonucleotide-based caspase-2 activator, much more can now be elucidated. For instance, one thing that could be unraveled is whether caspase-8 and Fas (CD95)-associated protein with death domain are indeed involved in caspase-2 activation as part of the death-inducing signaling complex. It is also becoming apparent that this enigmatic caspase may be important in the mechanisms behind which chemotherapeutic agents inhibit tumor cell growth. A better understanding of the true biological effects of this enzyme may indeed lead to more effective ways of managing tumors clinically. This review article briefly examines the different compounds capable of inducing activation of caspase-2 and proposes Dz13 as one that will be valuable for evaluation of the biological functions of caspase-2. PMID- 22077398 TI - Female metasternal gland odours mediate male aggregation in Rhodnius prolixus, a triatomid bug. AB - We investigated whether metasternal gland (MG) products mediate male aggregation during mating in Rhodnius prolixus (Heteroptera: Reduviidae) Stal, 1859, through selective occlusion of female MGs. Pairs of insects presenting intact MGs mated and other males aggregated around them confirming conclusions from previous studies. However, when female MGs were occluded, males did not aggregate. Conversely, the occlusion of male MGs did not affect aggregation of males. The present experiments demonstrated that the products emitted by the MGs of a mating R. prolixus female induce other males to aggregate around the mating pair. Aggregation behaviour of males probably results from the eventual release of volatiles from the female's MGs. We reinforce the hypothesis suggesting that the compounds produced by the MGs of R. prolixus act as sexual communication signals for this species. PMID- 22077401 TI - A bisferrocene-benzobisimidazole triad as a multichannel ditopic receptor for selective sensing of hydrogen sulfate and mercury ions. AB - The bisferrocene-benzobisimidazole triad behaves as a selective redox and fluorescent chemosensor for HSO(4)(-) and Hg(2+) ions, exhibiting an easily detectable signal change in both the redox potential of the ferrocene/ferrocinium redox couple and in the emission band which is red-shifted (Deltalambda = 10-13 nm) and enhanced in intensity (Chelation Enhanced Fluorescence, CHEF = 486-225) upon complexation with these ions, in EtOH solutions. PMID- 22077400 TI - Alteration of seed storage protein composition in soybean [Glycine max (L.) Merrill] mutant lines induced by gamma-irradiation mutagenesis. AB - This study investigated the alteration of seed storage proteins in soybean mutants induced by gamma-irradiation. Five soybean cultivars and four landraces were irradiated with 250 Gy of gamma rays to induce variability. The seed storage protein profiles of 414 genetic fixed mutants (M(12)-M(20)) having excellent agricultural traits were analyzed by SDS-PAGE. Among the 414 mutants, 58 were identifed as lacking lipoxygenase, 89 lacking the alpha' subunit, 113 lacking the alpha subunit, and 40 with an altered beta subunit. One hundred and forty-nine mutants lacked the A(3) subunit of glycinin. Fifty-four mutants showed higher trypsin inhibitor (TIA) activity, whereas 139 showed lower TIA activity compared to their original cultivars. The selected mutants with low amounts of antinutritional factors such as trypsin inhibitor, lipoxygenase, and alpha subunit will constitute genetic resources for improving soybean protein quality. PMID- 22077402 TI - Formation of polymeric toroidal-spiral particles. AB - Compared to spherical matrices, particles with well-defined internal structure provide large surface to volume ratio and predictable release kinetics for the encapsulated payloads. We describe self-assembly of polymeric particles, whereby competitive kinetics of viscous sedimentation, diffusion, and cross-linking yield a controllable toroidal-spiral (T-S) structure. Precursor polymeric droplets are splashed through the surface of a less dense, miscible solution, after which viscous forces entrain the surrounding bulk solution into the sedimenting polymer drop to form T-S channels. The intricate structure forms because low interfacial tension between the two miscible solutions is dominated by viscous forces. The biocompatible polymer, poly(ethylene glycol) diacrylate (PEG-DA), is used to demonstrate the solidification of the T-S shapes at various configurational stages by UV-triggered cross-linking. The dimensions of the channels are controlled by Weber number during impact on the surface, and Reynolds number and viscosity ratio during subsequent sedimentation. We anticipate applications of the T-S particle in drug delivery, wherein diffusion through these T-S channels and the polymer matrix would offer parallel release pathways for molecules of different sizes. Polyphosphate, as a model macromolecule, is entrained in T-S particles during their formation. The in vitro release kinetics of polyphosphate from the T-S particles with various channel length and width is reported. In addition, self-assembly of T-S particles occurs in a single step under benign conditions for delicate macromolecules, and appears conducive to scaleup. PMID- 22077403 TI - Foot loading characteristics during three fencing-specific movements. AB - Plantar pressure characteristics during fencing movements may provide more specific information about the influence of foot loading on overload injury patterns. Twenty-nine experienced fencers participated in the study. Three fencing-specific movements (lunge, advance, retreat) and normal running were performed with three different shoe models: Ballestra (Nike, USA), Adistar Fencing Lo (Adidas, Germany), and the fencers' own shoes. The Pedar system (Novel, Munich, Germany) was used to collect plantar pressures at 50 Hz. Peak pressures, force-time integrals and contact times for five foot regions were compared between four athletic tasks in the lunge leg and supporting leg. Plantar pressure analysis revealed characteristic pressure distribution patterns for the fencing movements. For the lunge leg, during the lunge and advance movements the heel is predominantly loaded; during retreat, it is the hallux. For the supporting leg, during the lunge and advance movements the forefoot is predominantly loaded; during retreat, it is the hallux. Fencing-specific movements load the plantar surface in a distinct way compared with running. An effective cushioning in the heel and hallux region would help to minimize foot loading during fencing-specific movements. PMID- 22077404 TI - Identification of genetic variation in 11 candidate genes of canine mammary tumour. AB - The incidence of canine mammary tumours (CMTs) differs significantly between breeds, strongly supporting an influence of genetic risk factors. We aimed at identifying germline genetic variations in mammary tumour-associated genes in dogs and survey whether these might alter the encoded proteins. We sequenced 11 genes (BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EGFR, ESR1, HER2, PTEN, STK11 and TP53) and screened for genetic variations. Sixty-four single nucleotide polymorphisms (SNPs) were identified. Nine of the coding SNPs were non-synonymous, of which four were located in gene regions conserved across four species. Three of the non synonymous SNPs might be damaging according to PolyPhen predictions. One of the indels identified has previously been associated with CMTs. Because of the founder effects, genetic drift and inbreeding in many dog breeds the allele frequencies of the genes studied are likely to vary significantly between breeds and contribute to the considerable difference in genetic risk associated with cancer. PMID- 22077405 TI - Detection of the tumour suppressor gene TP53 and expression of p53, Bcl-2 and p63 proteins in canine transmissible venereal tumour. AB - Canine transmissible venereal tumour (CTVT) is a neoplasm transmitted among healthy dogs by direct contact with injured skin and/or mucous tissue. This study aimed to identify the TP53 gene, messenger RNA (mRNA) as well as the expression of p53, Bcl-2 and p63 proteins in histological sections of 13 CTVT samples at different stages of evolution. The in situ hybridization (ISH) and in situ reverse transcriptase polymerase chain reaction (RT-PCR) assays were used, which showed the DNA homologous to TP53 and its respective mRNA in 92.3% of the samples. We detected p53, p63 and Bcl-2 proteins in most of the cell samples in different grades of intensity. In addition, 46% of the samples were in the progressive and 54% in the regression phase. This is the first description of these proteins and a detailed study of their role in CTVT cells needs to be addressed in or to verify how these cells undergo apoptosis. PMID- 22077406 TI - Single-agent gemcitabine chemotherapy in dogs with hepatocellular carcinomas. AB - The goal of this study was to determine the efficacy and tolerability of gemcitabine in dogs diagnosed with hepatocellular carcinoma (HCC). Eighteen dogs were examined retrospectively (4 massive HCC, 10 nodular HCC and 4 diffuse HCC). All dogs received gemcitabine at 350-400 mg m(-2) weekly for 5 weeks. Toxicity was graded using VCOG-CTCAE guidelines and response was monitored with serial abdominal ultrasounds. Fifteen dogs completed all five cycles. Toxicity was minimal and consisted of grade I/II vomiting, anorexia and diarrhoea and two episodes of grade III neutropenia. Median survival time for all dogs was 983 days. Median progression free interval was 971 days. Based on the results of this study, surgery remains the best treatment for HCC, despite incomplete resection. There was no improvement in the survival of those diagnosed with nonresectable HCC treated with gemcitabine chemotherapy. PMID- 22077407 TI - Cytogenetic studies in peripheral blood of bovines afflicted by papillomatosis. AB - Ten types of bovine papillomavirus (BPV) have been described and there are reports of viral transmission via blood. The presence of viral DNA in lymphocytes was described to be associated with chromosome instability in these cells. This study presents an evaluation of chromosome instability in short-term peripheral lymphocyte cultures from cows presenting skin papillomatosis, compared with asymptomatic infected animals and non-infected healthy bovines. In a total of 2203 cells, 918 (42%) showed at least one chromosome aberration: 42.7 (+/- 7.8) in animals with papillomatosis (BPV + W), 40.2 (+/- 11) in asymptomatic animals (BPV-W) and 4 (+/- 2) in control animals. Significant differences were found between the infected group (with or without symptoms) and the control group (P < 0.0001). The increased frequencies of chromosome aberrations suggest an interaction between the virus and host cell chromatin. PMID- 22077408 TI - Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma. AB - Polyamines are essential for cell proliferation. Their production is dysregulated in many cancers and polyamine depletion leads to tumour regression in mouse models of squamous cell carcinoma (SCC). The purpose of this study was to determine the maximally tolerated dose of the polyamine transport inhibitor, MQT 1426, when combined with the ornithine decarboxylase (ODC) inhibitor, DFMO, and to determine whether this therapy results in reduction in tumour polyamine levels. Thirteen cats with oral SCC received both drugs orally and serial tumour biopsies were obtained for polyamine measurement. Cats were monitored for response to therapy and toxicity. A maximum tolerated dose (MTD) of MQT 1426 when combined with DFMO was determined. Dose-limiting toxicity was vestibular in nature, but was fully reversible. Spermidine and total polyamine levels decreased significantly in tissues, two cats experienced objective tumour regression and six cats had stable disease. These results suggest that further study of polyamine depletion therapies is warranted. PMID- 22077409 TI - A randomized controlled study into the efficacy and toxicity of pegylated liposome encapsulated doxorubicin as an adjuvant therapy in dogs with splenic haemangiosarcoma. AB - Safety and efficacy of pegylated liposome encapsulated doxorubicin (PL-DOX) was compared with free doxorubicin as an adjuvant monotherapy in dogs with splenic haemangiosarcoma after splenectomy in a randomized prospective clinical trial. A total of 17 dogs in each group were treated. No significant difference in survival between the two treatments was found. The calculated median overall survival time for the 34 dogs was 166 days [95% confidence interval (CI) 148 184]. The 1/2 year and one-year survival was 41.2% (95% CI 24.8-56.9) and 22.7% (95% CI 9.9-37.4), respectively. In dogs treated with PL-DOX, a desquamating dermatitis like palmar-plantar erythrodysesthesia (PPES) was seen in two dogs, while three other dogs showed anaphylactic reactions. Cardiotoxicity was not seen in either treatment groups. PMID- 22077410 TI - Detection of tumour necrosis factor-alpha in dogs with lymphoma(*). AB - Tumour necrosis factor-alpha (TNF-alpha) production by malignant lymphoblasts has been identified in vitro and in vivo in mice and humans, respectively. The goals of this study were (1) to evaluate a novel single-sample TNF-alpha assay and (2) to determine whether TNF-alpha is increased in dogs with lymphoma prior to and following treatment. Canine TNF-alpha was analysed concurrently using the novel Siemens Immulite(r) single-sample automated ELISA and the previously validated Quantikine(r) standard ELISA. Serum from dogs with lymphoma and from breed-, age- and gender-matched control dogs was evaluated at two time points. Three of 25 (12%) dogs with lymphoma had detectable TNF-alpha at diagnosis, whereas none had detectable TNF-alpha following complete or partial remission. TNF-alpha was not detectable in control dogs. Despite 91% homology between human and canine TNF alpha, the Immulite(r) automated ELISA failed to detect canine TNF-alpha. Serum TNF-alpha appears to have limited value as a tumour marker in dogs with lymphoma. PMID- 22077411 TI - Prognostic value of regional lymph node status in canine mammary carcinomas. AB - In this study, we have determined the prognostic value of the presence of the micrometastases and metastases greater than 2 mm in the regional lymph nodes for bitches with mammary carcinomas. The study involved 51 dogs diagnosed with a single malignant epithelial tumour in the 4th or 5th mammary gland. All animals underwent regional mastectomy; the 4th and 5th mammary glands were removed together with the inguinal lymph node. The lymph nodes were examined immunohistochemically using the anti-cytokeratin antibody, clone AE1/AE3. The bitches were followed up every 6 months for 2 years after surgery to determine the disease-free survival (DFS) and overall survival (OS). The Kaplan-Meier analysis showed a statistically significant difference in DFS and OS only between the group of bitches without metastases and the group with lymph node metastases greater than 2 mm. No significant differences between these two groups versus bitches with lymph node micrometastases were found. PMID- 22077412 TI - Angiofibroma of the nasal cavity in 13 dogs. AB - This case series describes a rare entity, nasal angiofibroma, in 13 dogs that were presented to the University of Wisconsin, School of Veterinary Medicine from 1988 to 2000. All dogs in this case series presented with clinical signs and radiographic changes that were strongly suggestive of a locally invasive neoplasm. However, histopathology completed on transnostral core biopsy samples revealed benign appearing vascular proliferation with secondary lymphosuppurative inflammation was established despite cytologic criteria of malignancy present in five dogs. On the basis of the outcomes in this case series, nasal angiofibroma should be considered a differential for dogs presenting with clinical signs consistent with a malignant nasal tumour. PMID- 22077413 TI - Mast cells in canine mammary gland tumour: number, distribution and EPOR positivity. AB - Erythropoietin (EPO)-mediated mitogenic and anti-apoptotic effects involve all the cells expressing functional receptors for EPO (EPOR), as demonstrated by in vitro and in vivo studies. EPO shows pleiotropic effects and acts as an endogenous mediator of adaptive tissue response to metabolic stress protecting tissues from different injuries. Recently, the EPO/EPOR complex has been identified in several neoplastic cell lines and solid tumours. In this study, the authors investigated the mast cells (MCs) number, distribution and their immunoreactivity for EPOR in normal, dysplastic and neoplastic canine mammary gland. The results showed that MCs were more numerous in displastic glands compared with normal and neoplastic glands. As far as the EPOR immunoreactivity is concerned, we did not observe MCs reaction on cancer, in contrast with previously published data where epithelium of neoplastic gland showed an increase in EPOR expression along with the neoplastic progression. Overall, our results might be suggestive for MCs role in oncogenesis and offer new insight regarding to the expression of EPOR in mammary gland cancer in dog. PMID- 22077415 TI - Improving the energy and nutrient supply for common marmoset monkeys fed under long-term laboratory conditions. AB - BACKGROUND: Current knowledge about the optimal energy and nutrient supply for common marmoset monkeys (Callithrix jacchus) is scarce, and more information is needed for establishing the underlying nutritional concepts for facilitating longevity of this species as laboratory animals for biomedical research. METHODS: Two feeding experiments were conducted to yield fundamental data about feed acceptance, real feed intake, and feed preferences under laboratory conditions. Newly developed feeding concepts for marmoset monkeys were also examined in preliminary investigations to compare the outcomes with those of a commercial pelletized mixed feed. RESULTS: The first experiments showed preferences for main protein sources in the diets studied, specifically that plant proteins are more accepted than fish meal or egg protein as the main protein source. Several aroma supplements did not modify the acceptance and feed intake markedly. CONCLUSIONS: The newly developed feeding concept yielded promising preliminary data for long term studies of energy and nutrient supply under laboratory conditions. However, studies of the fundamental requirements are still needed. PMID- 22077414 TI - The promoting vibration in human heart lactate dehydrogenase is a preferred vibrational channel. AB - We examine whether the rate-promoting vibration of lactate dehydrogenase is a preferred axis of thermal energy transfer. While it seems plausible that such a mechanistically important motion is also a favored direction of energy transfer, none of the previous studies of rate-promoting vibrations in enzymatic catalysis have addressed this question. It is equally likely that the promoting vibration, though catalytically important, has no different properties than any other axis in the protein. Resolution of this issue is important for two reasons: First, if energy is transferred along this axis in a preferred fashion, it shows that the protein is engineered in a way that transfers thermal energy into a motion that is coupled to the chemical step. Second, the discovery of a preferred direction of thermal transfer provides a potential route to experimental verification of the promoting vibration concept. Our computational experiments are specifically designed to mimic potential laser experiment with the deposition of thermal energy in an active-site chromophore with subsequent measurement of temperature at various points in the protein. Our results indicate that the promoting vibration is indeed a preferred channel of energy transfer. In addition, we study the vibrational structure of the protein via the dynamical structure factor to show preferred vibrational motion along the promoting vibration axis is an inherent property of the protein structure via thermal fluctuations. PMID- 22077416 TI - Hydroxylated analogues of ATP-sensitive potassium channel openers belonging to the group of 6- and/or 7-substituted 3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides: toward an improvement in sulfonylurea receptor 1 selectivity and metabolism stability. AB - Diversely substituted 3-isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides are known to be potent KATP channel openers, with several drugs being selective for the SUR1/Kir6.2 channel subtype. This work examined the biological activity, tissue selectivity, and in vitro metabolic stability of hydroxylated analogues of 3-isopropylaminobenzothiadiazine dioxides. Because of the presence of a chiral center, the R and S isomers were prepared separately and characterized. R isomers were systematically found to be more potent and more selective than S isomers on pancreatic tissue (compared to vascular smooth muscle tissue), leading to compounds with an improved sulfonylurea receptor 1 (SUR1) selectivity. An in vitro metabolic study revealed that 7-chloro-3-isopropylamino-4H-1,2,4 benzothiadiazine 1,1-dioxide (1a) was rapidly biotransformed and led in part to a mixture of the corresponding (R)- and (S)-3-(1-hydroxy-2-propyl)amino-substituted derivatives. Radioisotopic experiments characterized one of the most potent and SUR1-selective enantiomers, (R)-7-chloro-3-(1-hydroxy-2-propyl)amino-4H-1,2,4 benzothiadiazine 1,1-dioxide 13a, as being a KATP channel opener. Moreover, 13a exhibited an enhanced metabolic stability. Such a compound can be considered as a new lead candidate displaying improved physicochemical (hydrosolubility) and pharmacological (tissue selectivity) properties as well as improved metabolic stability compared to its nonhydroxylated counterpart, 1a. PMID- 22077417 TI - Current strategies in the diagnosis of diffuse large B-cell lymphoma of the central nervous system. AB - Lymphomas can arise within the central nervous system (CNS) as primary CNS lymphoma (PCNSL) typically involving the brain and less often the leptomeninges, eyes, and spinal cord. In contrast to PCNSL, secondary CNS lymphoma (SCNSL) is considered to originate as quasi metastasis from systemic lymphoma spreading to the CNS. Both types of CNS lymphomas are predominantly tumours of the diffuse large B-cell type and represent aggressive diseases necessitating a rapid diagnosis. Following neuroimaging based on magnetic resonance imaging, stereotaxy and histopathological diagnosis of CNS lymphoma currently remain obligatory to plan treatment. However, progress in cytopathological, immunophenotypic, and molecular genetic analyses of the cerebrospinal fluid (CSF) has been achieved recently and potentially will facilitate lymphoma diagnosis in the future. This review describes the diagnostic procedures in patients with suspected CNS lymphomas, primarily PCNSL. In addition to a summary of the standard diagnostic work-up, an overview and discussion of current data on different techniques for evaluation of the CSF in CNS lymphoma are given. PMID- 22077418 TI - The estimation of body height from ulna length in healthy adults from different ethnic groups. AB - BACKGROUND: Assessments of nutritional status frequently incorporate a measure of height to evaluate a person's relative thinness or fatness. Because height is often difficult to quantify, it may be predicted from alternative anthropometric measurements, including ulna length. Little information is available about the accuracy of these predictions in an ethnically diverse population. The present study aimed to evaluate published equations for predicting height from ulna length in adults from different ethnic groups. METHODS: Ulna length and standing height were measured in a gender-stratified sample of 60 Asian, 69 Black and 65 White healthy volunteers, aged 21-65 years. Height was predicted from ulna length using the Malnutrition Universal Screening Tool (MUST) equations and compared against the measured values. Linear regression analysis was used to develop equations to estimate height from ulna length and to explore the relationship between height and ulna length in subgroups. RESULTS: The mean (SD) age for Asian, Black and White in men was 31.7 (11.0), 32.0 (10.3) and 38.6 (12.5) years and in women was 26.2 (5.4), 32.6 (8.9) and 35.7 (11.7); the mean (SD) height in men was 170.9 (5.2), 178.1 (7.3) and 176.3 (7.7) cm and in women was 157.7 (4.7), 164.0 (5.9) and 163.7 (6.2) cm. Ulna length and measured height were significantly correlated among all subgroups, except Asian women (r=0.11, P=0.57). The mean (SD) difference between predicted and measured height showed significant overestimates for Asian and Black men [4.0 (4.8) and 6.7 (5.3) cm] and Asian and Black women [6.4 (4.9) and 4.4 (4.9) cm] but not for White men and women. CONCLUSIONS: The MUST equations for predicting height from ulna length in healthy adults should be used with some caution among ethnically diverse populations, particularly in Asian women. PMID- 22077419 TI - Prophylactic administration of melatonin to the mother throughout pregnancy can protect against oxidative cerebral damage in neonatal rats. AB - OBJECTIVE: The purpose of this study was to investigate whether prophylactic administration of melatonin to the mother throughout pregnancy could protect against ischemia/reperfusion (I/R)-induced oxidative brain damage in neonatal rats. METHODS: The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. A sham operation was performed in control rats. Melatonin solution or vehicle alone was administrated orally throughout pregnancy. We collected brain mitochondria from neonatal rats, evaluated mitochondrial structure by electron microscopy, and measured the respiratory control index (RCI) as an indicator of mitochondrial respiratory activity as well as the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress. Histological analysis was performed at the Cornu Ammonis 1 (CA1) and Cornu Ammonis 3 (CA3) regions of the hippocampus. RESULTS: I/R significantly reduced the RCI and significantly elevated the concentration of TBARS. Melatonin treatment reversed these effects, resulting in values similar to that in untreated, sham-ischemic animals. Electron microscopic evaluation showed that the number of intact mitochondria decreased in the I/R group, while melatonin treatment preserved them. Histological analysis revealed a decrease in the ratio of normal to whole pyramidal cell number in the CA1 and CA3 regions in the I/R group. While melatonin administration protected against degeneration. CONCLUSIONS: These results indicate that prophylactic administration of melatonin to the mother throughout pregnancy may prevent I/R induced oxidative brain damage in neonatal rats. PMID- 22077420 TI - The antimicrobial effect of Iseganan HCl oral solution in patients receiving stomatotoxic chemotherapy: analysis from a multicenter, double-blind, placebo controlled, randomized, phase III clinical trial. AB - BACKGROUND: Cytotoxic chemotherapy induces changes in the oral microflora that may cause oral and systemic infections in myelosuppressed cancer patients. These complications prompted us to assess the antimicrobial activity of a topical Iseganan HCl mouthwash vs. placebo on the aerobic and facultatively anaerobic oral flora in these patients. METHODS: Two hundred and twenty-five chemotherapy patients were recruited into a randomized, double-blind, placebo-controlled trial, conducted at multiple centers. The study compared the antimicrobial efficacy of Iseganan HCl vs. placebo (95% of the Iseganan and 97% of the control group received myeloablative chemotherapy). Iseganan HCl 9 mg/3 ml was administered as a swish and swallow solution, six times daily for 21-28 days. Microbial cultures were made before and after the daily Iseganan mouth rinse on the first and final days of chemotherapy. RESULTS: The reduction in total microbial load after the first day of treatment was statistically significant (1.59 vs. 0.18 log10 CFU for the Iseganan HCl and placebo groups, respectively, P < 0.0001). Iseganan HCl rinse had a cumulative effect demonstrated by the significant difference between the two groups on the last day of the study (i.e. completion of Iseganan daily treatment) (P < 0.05). The reduction was mainly due to decreased densities of viridans streptococci, non-hemolytic streptococci, and yeasts. The minimal inhibitory concentration (MIC) of Iseganan HCl remained the same throughout the course of treatment. CONCLUSIONS: Topical Iseganan HCl significantly reduces the total oral aerobic bacterial, streptococcal, and yeast load. Its potential as an oral antimicrobial agent in preventing these types of infections is clear. PMID- 22077421 TI - Surface modification with poly(sulfobetaine methacrylate-co-acrylic acid) to reduce fibrinogen adsorption, platelet adhesion, and plasma coagulation. AB - Zwitterionic sulfobetaine methacrylate (SBMA) polymers were known to possess excellent antifouling properties due to high hydration capacity and neutral charge surface. In this study, copolymers of SBMA and acrylic acid (AA) with a variety of compositions were synthesized and were immobilized onto polymeric substrates with layer-by-layer polyelectrolyte films via electrostatic interaction. The amounts of platelet adhesion and fibrinogen adsorption were determined to evaluate hemocompatibility of poly(SBMA-co-AA)-modified substrates. Among various deposition conditions by modulating SBMA ratio in the copolymers and pH of the deposition solution, poly(SBMA(56)-co-AA(44)) deposited at pH 3.0 possessed the best hemocompatibility. This work demonstrated that poly(SBMA-co AA) copolymers adsorbed on polyelectrolyte-base films via electrostatic interaction improve hemocompatibility effectively and are applicable for various substrates including TCPS, PU, and PDMS. Furthermore, poly(SBMA-co-AA)-coated substrate possesses great durability under rigorous conditions. The preliminary hemocompatibility tests regarding platelet adhesion, fibrinogen adsorption, and plasma coagulation suggest the potential of this technique for the application to blood-contacting biomedical devices. PMID- 22077422 TI - Analysis of the volatile compounds of Teucrium flavum L. subsp. flavum (Lamiaceae) by headspace solid-phase microextraction coupled to gas chromatography with flame ionisation and mass spectrometric detection. AB - In this study, a headspace solid-phase microextraction (HS-SPME) method, in combination with gas chromatography flame ionisation detector and gas chromatography-mass spectrometry, has been developed for use in the analysis of the volatile compounds of Teucrium flavum L. subsp. flavum, a plant whose particular fragrance is used in the preparation of flavoured wines, bitters and liqueurs, or as a substitute for hops in the flavouring of beer. The tested fibres were 100 um poly(dimethylsiloxane) (PDMS), the 65 um PDMS/divinylbenzene (DVB) and 50/30 um DVB-carboxen-PDMS. The best fibre was found to be PDMS when working in the following conditions: 60 degrees C temperature, 30 min extraction time, 30 mg sample amount, 1 mm sample particle size. The HS-SPME method permitted the identification (95.8-97.8%) of 76 (dry) and 66 (fresh) different volatiles. In addition, we discovered that the presence of water in the sample can enhance the absolute quantity of alcoholic compounds such as 1-octen-3-ol and reduce the presence of esters such as methyl geranate. PMID- 22077423 TI - Altered microRNA expression profile with miR-27b down-regulation correlated with disease activity of oral lichen planus. AB - BACKGROUND: Increasing evidence indicates that microRNAs (miRNAs) play a vital role in the pathogenesis of inflammatory and autoimmune diseases. The objective of this study was to investigate the altered miRNA expression profile in patients with oral lichen planus (OLP) and determine the miR-27b expression. METHODS: We compared miRNA expression patterns in oral biopsy specimens from patients with OLP (n=3) with those from normal controls (n=3) using microarray technology. We further assessed the miR-27b expression in specimens from patients with OLP (n=53) against controls (n=34) using real-time quantitative PCR (RT-QPCR), and miR-27b expression in specimens from patients with OLP (n=15) against controls (n=12) using in situ hybridization (ISH). RESULTS: Using microarray analysis, a total of 46 differentially expressed miRNAs with more than 2-fold change were identified, including 8 up-regulated and 38 down-regulated miRNAs. Both RT-QPCR and ISH analyses revealed that miR-27b was significantly down-regulated in OLP tissue, and miR-27b expression was even more suppressed in atrophic-erosive OLP than in reticular OLP. In addition, miR-27b was found to be expressed in the epithelial keratinocyte layer of both normal and OLP tissues. CONCLUSION: These data indicate that miRNAs may be the novel candidate biomarkers for the implication of miRNAs in the pathogenesis of OLP. PMID- 22077424 TI - Primary cutaneous follicle centre lymphoma with atypical morphological features on hematoxylin-eosin stained images. PMID- 22077425 TI - Schizosaccharomyces pombe, unlike Saccharomyces cerevisiae, may not directly regulate nuclear-cytoplasmic transport of spliced tRNAs in response to nutrient availability. AB - Eukaryotic cells adapt to changes in nutrient levels by regulating key processes, such as gene transcription, ribosome biogenesis, and protein translation. Several studies have shown that nuclear export of tRNAs is also regulated in Saccharomyces cerevisiae and rat hepatoma H4IIE cells during nutrient stress. However, recent studies suggest that nutrient stress does not affect nuclear tRNA export in several mammalian cell lines, including rat hepatoma H4IIE. Furthermore, in contrast to previous studies, data reported more recently established that nuclear export of mature tRNAs derived from intron-containing pre-tRNAs, but not mature tRNAs made from intronless precursors, is affected by nutrient stress in several species of Saccharomyces, but not in the yeast Kluyveromyces lactis . Here, we provide evidence suggesting that Schizosaccharomyces pombe, like mammalian cells and K. lactis, but unlike Saccharomyces, do not directly regulate nuclear export of mature tRNAs made from intron-containing pre-tRNAs in response to nutrient stress. These studies collectively suggest that regulation of nuclear export of spliced tRNAs to the cytoplasm in response to nutrient availability may be limited to the genus Saccharomyces, which unlike other yeasts and higher eukaryotes produce energy for fermentative growth using respiration-independent pathways by downregulating the citric acid cycle and the electron transport chain. PMID- 22077426 TI - The potential benefits of applying a narrative analytic approach for understanding the experience of fibromyalgia: a review. AB - PURPOSE: People with fibromyalgia (FM), a medically unexplained illness, habitually experience widespread pain and fatigue. While some qualitative research has aimed to understand the experiences of people with FM, studies from a specific narrative perspective are particularly lacking. This review argues that future research could be significantly enhanced by studies which analyse the narratives of people with FM. METHOD: This argument is made through reference to an examination of the extant qualitative literature on the experience of FM and theories and narrative studies on chronic illnesses and identity. RESULTS: The empirical literature is reviewed from a narrative perspective; this assumes that the stories people tell reveal much about their identities and social worlds. As such, it is proposed that narrative analysis is particularly well suited for exploring issues of self and culture and for appreciating how meanings evolve over time. Further, it is also argued that consideration of these issues is particularly relevant for understanding the experience of FM given the enigmatic nature of the syndrome and its chronic course. CONCLUSIONS: The review concludes by emphasizing that narrative analysis is a valuable method which offers the potential for uncovering novel insights about the illness experience for these individuals. PMID- 22077427 TI - Intra-operative vs pre-operative endoscopic sphincterotomy in patients with gallbladder and common bile duct stones: cost-utility and value-of-information analysis. AB - BACKGROUND: Patients with gallbladder and common bile duct stones are generally treated by pre-operative endoscopic sphincterotomy (ES) followed by laparoscopic cholecystectomy (POES). Recently, a meta-analysis has shown that intra-operative ES during laparoscopic cholecystectomy (IOES) results in fewer complications than POES, with similar efficacy. The cost effectiveness of IOES versus POES is unknown. OBJECTIVE: The objective of this study was to compare the cost effectiveness of IOES versus POES from the UK NHS perspective. METHODS: A decision-tree model estimating and comparing costs to the UK NHS and QALYs gained following a policy of either IOES or POES was developed with a time horizon of 3 years. Uncertainty was investigated with probabilistic sensitivity analysis, and the expected value of perfect information (EVPI) and partial information (EVPPI) were also calculated. RESULTS: IOES was less costly than POES (approximately L623 per patient [year 2008 values]) and resulted in similar quality of life (+0.008 QALYs per patient) as POES. Given a willingness-to-pay threshold of L20 000 per QALY gained, there was a 92.9% probability that IOES is cost effective compared with POES. Full implementation of IOES could save the NHS L2.8 million per annum. At a willingness to pay of L20 000 per QALY gained, the 10-year population EVPI was estimated at L0.6 million. CONCLUSIONS: IOES appears to be cost effective compared with POES. PMID- 22077428 TI - The power of reviews and marker vaccines. PMID- 22077429 TI - Investigating the adhesion of water droplets at low temperatures. AB - Adhesion of droplets to solid surfaces at low temperatures is crucial for antifogging and antifreezing, etc. So far, most reports on adhesion measurements have been carried out in air-liquid-solid systems, but it remains difficult to precisely investigate the adhesion at low temperatures due to the uncontrollable condensation. On the basis of the liquid-liquid-solid system, a new method to measure the adhesion of water droplets at low temperatures was developed and employed. Moreover, the reported method could be viable in other liquid-liquid solid systems with wider temperature window; thus, it will find applications in broad fields such as crude oil recovery, ore-dressing, and transfer printing. PMID- 22077431 TI - A brief history of this journal. PMID- 22077430 TI - Mechanisms and clinical implications of thrombosis in paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease characterized by a clone of blood cells lacking glycosyl phosphatidylinositol (GPI)-anchored proteins at the cell membrane. Deficiency of the GPI-anchored complement inhibitors CD55 and CD59 on erythrocytes leads to intravascular hemolysis upon complement activation. Apart from hemolysis, another prominent feature is a highly increased risk of thrombosis. Thrombosis in PNH results in high morbidity and mortality. Often, thrombosis occurs at unusual locations, with the Budd-Chiari syndrome being the most frequent manifestation. Primary prophylaxis with vitamin K antagonists reduces the risk but does not completely prevent thrombosis. Eculizumab, a mAb against complement factor C5, effectively reduces intravascular hemolysis and also thrombotic risk. Therefore, eculizumab treatment has dramatically improved the prognosis of PNH. The mechanism of thrombosis in PNH is still unknown, but the highly beneficial effect of eculizumab on thrombotic risk suggests a major role for complement activation. Additionally, a deficiency of GPI-anchored proteins involved in hemostasis may be implicated. PMID- 22077432 TI - Myocardial remodelling in left ventricular atrophy induced by caloric restriction. AB - Changes in body weight due to changes in food intake are reflected by corresponding changes in the cardiac phenotype. Despite a growing body of literature on cardiac hypertrophy associated with obesity, little is known on the atrophic remodelling of the heart associated with calorie restriction. We hypothesized that, besides the cardiomyocyte compartment, capillaries and nerve fibres are involved in the atrophic process. C57Bl6 mice were kept on normal diet (control group) or at a calorie-restricted diet for 3 or 7 days (n = 5 each). At the end of the protocol, mice were killed and the hearts were processed for light and electron microscopic stereological analysis of cardiomyocytes, capillaries and nerve fibres. Body, heart and left ventricular weight were significantly reduced in the calorie-restricted animals at 7 days. Most morphological parameters were not significantly different at 3 days compared with the control group, but at 7 days most of them were significantly reduced. Specifically, the total length of capillaries, the volume of cardiomyocytes as well as their subcellular compartments and the interstitium were proportionally reduced during caloric restriction. No differences were observed in the total length or the mean diameter of axons between the cardiomyocytes. Our data indicate that diet-induced left ventricular atrophy leads to a proportional atrophic process of cardiomyocytes and capillaries. The innervation is not involved in the atrophic process. PMID- 22077433 TI - Trend of contact allergy to cosmetic ingredients in Thais over a period of 10 years. AB - BACKGROUND: Contact allergy to cosmetic ingredients is common. However, there are no recent comprehensive studies on contact allergy to cosmetic ingredients in Asia. OBJECTIVES: To identify positive patch test reactions in patients tested at Siriraj Hospital, Bangkok, Thailand to allergens present in cosmetics. METHODS: A retrospective review of medical records from the outpatient contact dermatitis clinic was conducted from January 1999 to December 2008. Patients with at least one positive patch test reaction to allergens associated with cosmetic ingredients were studied. The results were evaluated using Pearson's chi(2) -test with Yates' continuity correction or Fisher's exact test where appropriate,and a p-value <0.002 was considered to be statistically significant by Bonferroni correction. RESULTS: There were 1247 cases (239 males and 1008 females; mean age 38.5 years). Fragrance chemicals and preservatives were the most commonly recognized cosmetic allergens. Ammoniated mercury was the only allergen that showed a significantly increased frequency over the 10-year period (p = 0.0008). CONCLUSIONS: Our study showed that ammoniated mercury is an emerging cosmetic allergen, showing an increased prevalence in recent years in Thailand. A focus is required on emerging cosmetic allergens and what may account for the upward trend of cosmetic contact dermatitis. PMID- 22077434 TI - The 'overall yield' with the baseline series - a useful addition to the array of MOAHLFA factors describing departmental characteristics of patch tested patients. AB - BACKGROUND: The proportion of patients with a positive patch test reaction to at least one allergen from the baseline series differs between departments. OBJECTIVES: To further define the above mentioned proportion, termed the 'P' measure, to examine factors associated with this measure, to describe its variation over time and between centres, and to discuss possible uses. PATIENTS AND METHODS: Eighteen departments have been 'long-term' participants in the Information Network of Departments of Dermatology (IVDK; www.ivdk.org), that is, since 1995 (1997 in two cases). In these departments, 80 919 consultations for patch testing with the baseline series, in the composition of the series valid at that time, were documented until December 2009. Bivariate and multifactorial analyses addressed factors associated with being patch test-positive to at least one baseline series allergen. RESULTS: Of the study population, 46.5% had at least one positive test reaction, with considerable variation being seen between centres and a general decline during the study period. Among other factors, female sex, occupational causation and a high suspicion of allergic contact dermatitis were significantly associated with having at least one positive patch test reaction to the baseline series. CONCLUSIONS: The 'P' measure should prove useful as another perspective on departmental characteristics, and should be reported along with established variables (MOAHLFA index). PMID- 22077435 TI - Excessive nickel release from mobile phones--a persistent cause of nickel allergy and dermatitis. AB - BACKGROUND: Despite the political intention to limit nickel allergy and dermatitis in Europeans, nickel allergy remains frequent. There are several explanations for the persistence of nickel allergy and dermatitis, including the increasing use of mobile phones. Before regulation of nickel release from mobile phones, we showed that eight (19.5%) of 41 mobile phones marketed in Denmark between 2003 and 2007 released nickel in concentrations that may result in nickel allergy and dermatitis. In 2009, the EU Nickel Directive was revised to include nickel-releasing mobile phones. OBJECTIVES: To investigate the proportion of mobile phones sold in Denmark that release nickel after regulation. METHODS: Metallic parts from 50 randomly selected mobile phones currently for sale in Denmark were tested for nickel release by use of the dimethylglyoxime (DMG) nickel spot test. RESULTS: Nine (18%) phones showed at least one positive DMG test reaction and two phones had more than one DMG test-positive spot. CONCLUSIONS: Apparently, the proportion of mobile phones with significant nickel release remains unchanged, despite the 2009 revision of the EU Nickel Directive. We encourage manufacturers to measure nickel release from metallic components used in the assembly of mobile phones to ensure safe products. PMID- 22077436 TI - Allergic contact dermatitis caused by sodium dehydroacetate, not hyaluronic acid, in Ialuset(r) cream. PMID- 22077437 TI - Widespread contact dermatitis caused by urushiol in kintsugi. PMID- 22077438 TI - Contact urticaria caused by carvone in toothpaste. PMID- 22077439 TI - Can reliable information sources be trusted? PMID- 22077440 TI - Fragrances in topical over-the-counter medicaments - a loophole in EU legislation should be closed. PMID- 22077441 TI - Allergic contact dermatitis caused by bis-diglycerylpolyacyladipate-2 (Softisan(r) 649) owing to its 12-hydroxystearic acid content. PMID- 22077442 TI - Cutaneous myoepithelioma arising within hidradenoma of the scalp. AB - A 62-year-old man presented with a 2-year history of a 2-cm cystic mass involving his occiput. There had been recent enlargement, and the clinical impression was that of a pilar cyst. Histopathological sections showed a partially dermal solid and cystic proliferation. The tumor contained areas of glandular differentiation with cuboidal to columnar cells lining luminal and cystic spaces. A concurrent spindle cell proliferation was seen interspersed between glands and also formed broad, cellular sheets of cells. The stroma was sclerotic and without chondroid or myxoid elements. Immunohistochemistry showed that the spindled cells expressed S100 protein, cytokeratin and smooth muscle myosin. The immunohistochemical profile and the relationship with ductal elements supported myoepithelial differentiation. The proliferation warranted the diagnosis of myoepithelioma arising from a hidradenoma, which to our knowledge has not been previously described. In addition to discussing this case, we provide a brief review of epithelial-myoepithelial neoplasms encountered in the skin. PMID- 22077443 TI - Identification of 4-hydroxy-2-nonenal-histidine adducts that serve as ligands for human lectin-like oxidized LDL receptor-1. AB - LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) is an endothelial scavenger receptor that is important for the uptake of OxLDL (oxidized low density lipoprotein) and contributes to the pathogenesis of atherosclerosis. However, the precise structural motifs of OxLDL that are recognized by LOX-1 are unknown. In the present study, we have identified products of lipid peroxidation of OxLDL that serve as ligands for LOX-1. We used CHO (Chinese-hamster ovary) cells that stably express LOX-1 to evaluate the ability of BSA modified by lipid peroxidation to compete with AcLDL (acetylated low-density lipoprotein). We found that HNE (4-hydroxy-2-nonenal)-modified proteins most potently inhibited the uptake of AcLDL. On the basis of the findings that HNE-modified BSA and oxidation of LDL resulted in the formation of HNE-histidine Michael adducts, we examined whether the HNE-histidine adducts could serve as ligands for LOX-1. The authentic HNE-histidine adduct inhibited the uptake of AcLDL in a dose-dependent manner. Furthermore, we found the interaction of LOX-1 with the HNE-histidine adduct to have a dissociation constant of 1.22*10(-8) M using a surface plasmon resonance assay. Finally, we showed that the HNE-histidine adduct stimulated the formation of reactive oxygen species and activated extracellular-signal-regulated kinase 1/2 and NF-kappaB (nuclear factor kappaB) in HAECs (human aortic endothelial cells); these signals initiate endothelial dysfunction and lead to atherosclerosis. The present study provides intriguing insights into the molecular details of LOX-1 recognition of OxLDL. PMID- 22077444 TI - On stability, chirality measures, and theoretical VCD spectra of the chiral C58X2 fullerenes (X = N, B). AB - The stability of all 23 C(58)N(2) and C(58)B(2) heterofullerenes in the singlet and triplet states was determined at the B3LYP/6-31G** level. In equilibrium mixture the achiral (1,4) C(58)N(2) isomer would be populated in ca. 95.8%, the chiral (1,16) one in ca. 3.3%, and the achiral (1,4) C(58)B(2) in 100%, whereas all triplet state isomers are less stable. Fourteen out of 23 C(58)X(2) are chiral. Four different chirality measures were calculated by our own CHIMEA program: pure geometrical, labeled, mass, and charge. Intercorrelations between the measures for all chiral compounds indicate that the pure geometrical chirality measure is unstable and should not be used in QSAR predictions of the other molecular properties, while the labeled and mass-weighted ones are promising QSAR descriptors. For each chiral C(58)N(2) molecule, some very strong VCD bands, of intensity comparable with that in the IR spectra, can serve in identification and characterization of the isomers. PMID- 22077445 TI - Stereotactic radiosurgery for arteriovenous malformations, Part 3: outcome predictors and risks after repeat radiosurgery. AB - OBJECT: The object of this study was to evaluate the outcomes and risks of repeat stereotactic radiosurgery (SRS) for incompletely obliterated cerebral arteriovenous malformations (AVMs). METHODS: Between 1987 and 2006, Gamma Knife surgery was performed in 996 patients with AVMs. During this period, repeat SRS was performed in 105 patients who had incompletely obliterated AVMs at a median of 40.9 months after initial SRS (range 27.5-139 months). The median AVM target volume was 6.4 cm(3) (range 0.2-26.3 cm(3)) at initial SRS but was reduced to 2.3 cm(3) (range 0.1-18.2 cm(3)) at the time of the second procedure. The median margin dose at both initial SRS and repeat SRS was 18 Gy. RESULTS: The actuarial rate of total obliteration by angiography or MR imaging after repeat SRS was 35%, 68%, 77%, and 80% at 3, 4, 5, and 10 years, respectively. The median time to complete angiographic or MR imaging obliteration after repeat SRS was 39 months. Factors associated with a higher rate of AVM obliteration were smaller residual AVM target volume (p = 0.038) and a volume reduction of 50% or more after the initial procedure (p = 0.014). Seven patients (7%) had a hemorrhage in the interval between initial SRS and repeat SRS. Seventeen patients (16%) had hemorrhage after repeat SRS and 6 patients died. The cumulative actuarial rates of new AVM hemorrhage after repeat SRS were 1.9%, 8.1%, 10.1%, 10.1%, and 22.4% at 1, 2, 3, 5, and 10 years, respectively, which translate to annual hemorrhage rates of 4.05% and 1.79% of patients developing new post-repeat-SRS hemorrhages per year for Years 0-2 and 2-10 following repeat SRS. Factors associated with a higher risk of hemorrhage after repeat SRS were a greater number of prior hemorrhages (p = 0.008), larger AVM target volume at initial SRS (p = 0.010), larger target volume at repeat SRS (p = 0.002), initial AVM volume reduction less than 50% (p = 0.019), and a higher Pollock-Flickinger score (p = 0.010). Symptomatic adverse radiation effects developed in 5 patients (4.8%) after initial SRS and in 10 patients (9.5%) after repeat SRS. Prior embolization (p = 0.022) and a higher Spetzler-Martin grade (p = 0.004) were significantly associated with higher rates of adverse radiation effects after repeat SRS. Delayed cyst formation occurred in 5 patients (4.8%) at a median of 108 months after repeat SRS (range 47-184 months). CONCLUSIONS: Repeat SRS for incompletely obliterated AVMs increases the eventual obliteration rate. Hemorrhage after obliteration did not occur in this series. The best results for patients with incompletely obliterated AVMs were seen in patients with a smaller residual nidus volume and no prior hemorrhages. PMID- 22077446 TI - Using imaging to identify psychogenic parkinsonism before deep brain stimulation surgery. Report of 2 cases. AB - The frequency with which patients with atypical parkinsonism and advanced motor symptoms undergo deep brain stimulation (DBS) procedures is unknown. However, the potential exposure of these patients to unnecessary surgical risks makes their identification critical. As many as 15% of patients enrolled in recent early Parkinson disease (PD) trials have been found to lack evidence of a dopaminergic deficit following PET or SPECT imaging. This suggests that a number of patients with parkinsonism who are referred for DBS may not have idiopathic PD. The authors report on 2 patients with probable psychogenic parkinsonism who presented for DBS surgery. They found that both patients had normal caudate and putamen [(18)F]-fluorodopa uptake on PET imaging, along with normal expression of specific disease-related metabolic networks for PD and multiple system atrophy, a common form of atypical neurodegenerative parkinsonism. The clinical and PET findings in these patients highlight the role of functional imaging in assisting clinical decision making when the diagnosis is uncertain. PMID- 22077447 TI - Stereotactic radiosurgery for arteriovenous malformations, Part 6: multistaged volumetric management of large arteriovenous malformations. AB - OBJECT: The object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery. METHODS: In 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm(3). Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8-13.8 months). The median target volume was 11.5 cm(3) (range 4.0-26 cm(3)) in the first-stage SRS and 9.5 cm(3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both stages. RESULTS: In 17 patients, AVM obliteration was confirmed after 2-4 SRS procedures at a median follow-up of 87 months (range 0.4 209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33-113 months) after the initial 2 stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0-1, 1 5, and 5-10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS. CONCLUSIONS: Prospective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volume-staged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS. PMID- 22077448 TI - Role of radiosurgery for arteriovenous malformations. PMID- 22077449 TI - Radiosurgery. PMID- 22077450 TI - Stereotactic radiosurgery for arteriovenous malformations, Part 5: management of brainstem arteriovenous malformations. AB - OBJECT: In this paper, the authors' goal was to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the medulla, pons, and midbrain. METHODS: Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 67 patients had AVMs in the brainstem. In this series, 51 patients (76%) had a prior hemorrhage. The median target volume was 1.4 cm(3) (range 0.1-13.4 cm(3)). The median margin dose was 20 Gy (range 14-25.6 Gy). RESULTS: Obliteration of the AVMs was eventually documented in 35 patients at a median follow-up of 73 months (range 6 269 months). The actuarial rates of documentation of total obliteration were 41%, 70%, 70%, and 76% at 3, 4, 5, and 10 years, respectively. Higher rates of AVM obliteration were associated only with a higher margin dose. Four patients (6%) suffered a hemorrhage during the latency period, and 2 patients died. The rate of AVM hemorrhage after SRS was 3.0%, 3.0%, and 5.8% at 1, 5, and 10 years, respectively. The overall annual hemorrhage rate was 1.9%. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 7 patients (10%) after SRS, and a delayed cyst developed in 2 patients (3%). One patient died at an outside institution with symptoms of AREs and unrecognized hydrocephalus. Higher 12-Gy volumes and higher Spetzler-Martin grades were associated with a higher risk of symptomatic AREs. Ten of 22 patients who had ocular dysfunction before SRS had improvement, 9 were unchanged, and 3 were worse due to AREs. Eight of 14 patients who had hemiparesis before SRS improved, 5 were unchanged, and 1 was worse. CONCLUSIONS: Although hemorrhage after obliteration did not occur in this series, patients remained at risk during the latency interval until obliteration occurred. Thirty-eight percent of the patients who had neurological deficits due to prior hemorrhage improved. Higher dose delivery in association with conformal and highly selective SRS is required for safe and effective radiosurgery. PMID- 22077451 TI - Stereotactic radiosurgery for arteriovenous malformations, Part 4: management of basal ganglia and thalamus arteriovenous malformations. AB - OBJECT: The authors conducted a study to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the basal ganglia and thalamus. METHODS: Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 56 patients had AVMs of the basal ganglia and 77 had AVMs of the thalamus. In this series, 113 (85%) of 133 patients had a prior hemorrhage. The median target volume was 2.7 cm(3) (range 0.1-20.7 cm(3)) and the median margin dose was 20 Gy (range 15-25 Gy). RESULTS: Obliteration of the AVM eventually was documented on MR imaging in 78 patients and on angiography in 63 patients in a median follow-up period of 61 months (range 2-265 months). The actuarial rates documenting total obliteration after radiosurgery were 57%, 70%, 72%, and 72% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration included AVMs located in the basal ganglia, a smaller target volume, a smaller maximum diameter, and a higher margin dose. Fifteen (11%) of 133 patients suffered a hemorrhage during the latency period and 7 patients died. The rate of post-SRS AVM hemorrhage was 4.5%, 6.2%, 9.0%, 11.2%, and 15.4% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 4.7%. When 5 patients with 7 hemorrhages occurring earlier than 6 months after SRS were removed from this analysis, the annual hemorrhage rate decreased to 2.7%. Larger volume AVMs had a higher risk of hemorrhage after SRS. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 6 patients (4.5%), and in 1 patient a delayed cyst developed 56 months after SRS. No patient died of AREs. Factors associated with a higher risk of symptomatic AREs were larger target volume, larger maximum diameter, lower margin dose, and a higher Pollock-Flickinger score. CONCLUSIONS: Stereotactic radiosurgery is a gradually effective and relatively safe management option for deep-seated AVMs in the basal ganglia and thalamus. Although hemorrhage after obliteration did not occur in the present series, patients remain at risk during the latency interval between SRS and obliteration. The best candidates for SRS are patients with smaller volume AVMs located in the basal ganglia. PMID- 22077452 TI - Stereotactic radiosurgery for arteriovenous malformations, Part 1: management of Spetzler-Martin Grade I and II arteriovenous malformations. AB - OBJECT: The aim of this paper was to define the outcomes and risks of stereotactic radiosurgery (SRS) for Spetzler-Martin Grade I and II arteriovenous malformations (AVMs). METHODS: Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs, including 217 patients with AVMs classified as Spetzler-Martin Grade I or II. The median maximum diameter and target volumes were 1.9 cm (range 0.5-3.8 cm) and 2.3 cm(3) (range 0.1-14.1 cm(3)), respectively. The median margin dose was 22 Gy (range 15-27 Gy). RESULTS: Arteriovenous malformation obliteration was confirmed by MR imaging in 148 patients and by angiography in 100 patients with a median follow-up of 64 months (range 6-247 months). The actuarial rates of total obliteration determined by angiography or MR imaging after 1 SRS procedure were 58%, 87%, 90%, and 93% at 3, 4, 5, and 10 years, respectively. The median time to complete MR imaging determined obliteration was 30 months. Factors associated with higher AVM obliteration rates were smaller AVM target volume, smaller maximum diameter, and greater marginal dose. Thirteen patients (6%) suffered hemorrhages during the latency period, and 6 patients died. Cumulative rates of AVM hemorrhage 1, 2, 3, 5, and 10 years after SRS were 3.7%, 4.2%, 4.2%, 5.0%, and 6.1%, respectively. This corresponded to rates of annual bleeding risk of 3.7%, 0.3%, and 0.2% for Years 0-1, 1-5, and 5-10, respectively, after SRS. The presence of a coexisting aneurysm proximal to the AVM correlated with a significantly higher hemorrhage risk. Temporary symptomatic adverse radiation effects developed in 5 patients (2.3%) after SRS, and 2 patients (1%) developed delayed cysts. CONCLUSIONS: Stereotactic radiosurgery is a gradually effective and relatively safe option for patients with smaller volume Spetzler-Martin Grade I or II AVMs who decline initial resection. Hemorrhage after obliteration did not occur in this series. Patients remain at risk for a bleeding event during the latency interval until obliteration occurs. Patients with aneurysms and an AVM warrant more aggressive surgical or endovascular treatment to reduce the risk of a hemorrhage in the latency period after SRS. PMID- 22077454 TI - Association fibers connecting the Broca center and the lateral superior frontal gyrus: a microsurgical and tractographic anatomy. AB - OBJECT: Recently, intraoperative mapping has disclosed that, in addition to the classic language centers (that is, the Broca and Wernicke centers), other cortical regions may also play an important role in language organization. In the prefrontal cortex, although the lateral superior frontal gyrus (LSFG) could have language-related functions, there are no detailed reports that demonstrate the anatomical connection between the LSFG and other well-known language cortices, such as the Broca center. To show the existence of the structural connection, white matter association fibers between the inferior frontal gyrus (IFG) and the LSFG were examined using fiber dissection (FD) and diffusion tensor (DT) imaging based tractography. METHODS: Eight cadaveric cerebral hemispheres were dissected to reveal the association fibers between the IFG and LSFG. The DT imaging-based tractography studies targeting the prefrontal cortex were obtained in 53 right handed patients who had no organic cerebral lesions. RESULTS: The association fiber tract between Brodmann area 44/45 (the Broca center in the dominant hemisphere) and LSFG were detected in all specimens by FD. In the DT imaging based tractography studies, the tract was identified in all patients bilaterally, except for the 4 in whom the tract was detected only in the left hemisphere. This tract was spread significantly wider in the left than in the right hemisphere, and left lateralization was evident in male patients. CONCLUSIONS: Based on its character, this tract was named the Broca-LSFG pathway. These findings suggest a close relationship between this pathway and language organization. The structural anatomy of the Broca-LSFG pathway may explain speech disturbances induced by LSFG stimulation that are sometimes observed during intraoperative language mapping. PMID- 22077455 TI - Stereotactic radiosurgery for arteriovenous malformations. PMID- 22077456 TI - Severe neonatal jaundice: is it a rare event in Australia? AB - Hyperbilirubinaemia is common in the newborn period, and while the vast majority of babies are unaffected, significant neurological impairment remains a risk associated with extremely high levels of bilirubin. There is concern internationally that the number of babies affected by severe neonatal hyperbilirubinaemia may be increasing. This review describes the most current published data pertaining to the incidence and causes of severe neonatal hyperbilirubinaemia in order to determine whether concern regarding the possible re-emergence of kernicterus in Australia is warranted. Seven incidence studies conducted internationally between 1988 and 2005 identify an estimated incidence of severe neonatal jaundice of between 7.1 and 45 per 100,000 births and of kernicterus at 0.4-2.7. Major pathophysiological causes or associations include ABO and other blood group incompatibility, glucose-6-phoshate-dehydrogenase deficiency, infection and haemolysis of other causes including spherocytosis. Other factors associated with poor outcomes include prematurity, male gender, ethnicity, breastfeeding and early hospital discharge. The management of severe neonatal jaundice requires multifaceted risk quantification in addition to the availability of adequate surveillance, particularly in the context of early hospital discharge. It is of concern that currently there is a paucity of incidence data in Australia relating to this potentially devastating yet generally preventable condition. Therefore, a surveillance study has been initiated through the Australian Paediatric Surveillance Unit. It is anticipated that these data will accurately define the incidence in Australia and hopefully guide strategies to prevent a condition that we may have prematurely considered to be of historical interest only. PMID- 22077457 TI - Cytotoxic and antimicrobial aporphine alkaloids from Fissistigma poilanei (Annonaceae) collected in Vietnam. AB - Two new aporphine alkaloids: 8-hydroxy-9-methoxy-1,2-methylenedioxyaporphine (1) and 8-hydroxy-3,9-dimethoxy-1,2-methylenedioxyaporphine (2) were isolated from the ethyl acetate extract of Fissistigma poilanei along with five known compounds: oxocrebanine (3), kuafumine (4), (2R,3R)-3',4',5,7 tetrahydroxydihydroflavonol-3-O-alpha-L-rhamnopyranoside (5), (+)-catechin 3-O alpha-L-rhamnopyranoside (6) and quercetine 3,7-dimethoxy-3'-O-alpha-L rhamnopyranosyl-(1 -> 2)-beta-D-glucopyranoside (7). These two new aporphine alkaloids exhibited a moderate cytotoxic activity against four human cancer cell lines (KB, Hep-G2, MCF-7, LU) as well as antimicrobial activity against Lactobacillus fermentum, Enterococcus faecium, Staphylococcus aureus and Bacillus subtillis. PMID- 22077458 TI - Modulating antibacterial properties using nanotechnology. PMID- 22077460 TI - Sensitizing of gemcitabine-resistant human leukemia cells by stearoyl gemcitabine nanoparticles . PMID- 22077461 TI - Interview: Nanomedicine in oncology: miniaturized means to an enormous end. Interviewed by Cara Sutton. PMID- 22077462 TI - In vivo real-time fluorescence visualization and brain-targeting mechanisms of lipid nanocarriers with different fatty ester:oil ratios. AB - AIMS: The objective of the present work was to investigate the influence of the inner cores of lipid nanocarriers on the efficiency of brain targeting. Cetyl palmitate and squalene were respectively chosen as the solid lipid and liquid oil in the inner phase of the nanocarriers. MATERIALS & METHODS: Nanoparticulate systems with different cetyl palmitate/squalene ratios were compared by evaluating the size, zeta potential, molecular environment, and mobility of lipids in the systems. RESULTS: The particulate diameter ranged from 190 to 210 nm, with systems containing 100% cetyl palmitate in the matrix (solid lipid nanoparticles [SLN]) showing the smallest size, followed by systems with both cetyl palmitate and squalene (nanostructured lipid carriers [NLC]) and with 100% squalene (lipid emulsions [LE]). A cationic surfactant, Forestall, was used to produce a positive surface charge of 40-55 mW. The in vitro release was evaluated using various dyes located in different phases of the nanocarriers. The release of sulforhodamine B occurred in a sustained manner from the shell of the nanocarriers. The in vivo brain distribution of lipid nanosystems after an intravenous injection into rats was monitored by a real-time fluorescence imaging system. LE showed higher brain accumulation than SLN and NLC. NLC only exhibited a slightly higher brain accumulation compared with the aqueous control. Incorporation of sulforhodamine B into LE could prolong its retention in the brain from 20 to 50 min. The results were further confirmed by imaging the entire brain and brain slices. The specific association of lipid nanocarriers with rat brain endothelial cells (bEnd3) was demonstrated using fluorescence microscopy. The cellular uptake of LE and SLN was higher compared with NLC and the aqueous control. LE were observed to be internalized by cells through caveola-mediated and macropinocytotic energy-dependent endocytosis. CONCLUSION: The experimental profiles indicated that LE with moderate additives are a promising brain targeting nanocarrier. The composition of the lipid matrix played a significant role in delivering compounds to the brain. PMID- 22077463 TI - Magnetic targeting strategies in gene delivery. AB - Gene delivery is a process of the insertion of transgenes into cells with the purpose to obtain the expression of encoded protein. The therapeutic application of this process is termed gene therapy, which is becoming a promising instrument to treat genetic and acquired diseases. Although numerous methods of gene transfer have already been developed, including biological, physical and chemical approaches, the optimal strategy has to be discovered. Importantly, it should be effective, selective and safe to be translated to the clinic. Magnetic targeting has been demonstrated as an effective strategy to decrease side effects of gene transfer, while increasing the selectivity and efficiency of the applied vector. This article will focus on the latest progress in the development of different magnetic vectors, based on both viral and nonviral gene delivery agents. It will also include a description of magnetic targeting applications in stem cells and in vivo, which has gained interest in recent years due to the rapid development of technology. PMID- 22077465 TI - Design of self-assembling peptides and their biomedical applications. AB - Combining physics, engineering, chemistry and biology, we can now design, synthesize and fabricate biological nanomaterials at the molecular scale using self-assembling peptide systems. These peptides have been used for fabrication of nanomaterials, including nanofibers, nanotubes and vesicles, nanometer-thick surface coating and nanowires. Some of these peptides are used for stabilizing membrane proteins and drug delivery, and others provide a more permissive environment for 3D cell culture, tissue engineering and repair of tissues in regenerative medicine. Self-assembling peptides are also useful for fabricating a wide spectrum of exquisitely fine architectures, nanomaterials and nanodevices for nanomedicine and nanobiotechnology. These peptide systems lie at the interface between molecular biology, chemistry, materials science and engineering. The studies of designed self-assembling peptides and their applications will help us to understand nature?s enormous power and how to apply it to benefit other disciplines and society. PMID- 22077464 TI - Improving delivery and efficacy of nanomedicines in solid tumors: role of tumor priming. AB - Effectiveness of nanomedicines in cancer therapy is limited in part by inadequate delivery and transport in tumor interstitium. This article reviews the experimental approaches to improve nanomedicine delivery and transport in solid tumors. These approaches include tumor vasculature normalization, interstitial fluid pressure modulation, enzymatic extracellular matrix degradation, and apoptosis-inducing tumor priming technology. We advocate the latter approach due to its ease and practicality (accomplished with standard-of-care chemotherapy, such as paclitaxel) and tumor selectivity. Examples of applying tumor priming to deliver nanomedicines and to design drug/RNAi-loaded carriers are discussed. PMID- 22077466 TI - Lipid-based nanoformulation of irinotecan: dual mechanism of action allows for combination chemo/angiogenic therapy. AB - A number of studies have outlined the antiangiogenic effects of cytotoxic agents when administered frequently at low doses. These studies suggest that the effect of the cytotoxic agent is on the vasculature within the tumor and it is assumed that there is little or negligible cytotoxicity. Liposomal drug delivery systems have the ability to provide a dual mechanism of activity where tumor accumulation can deliver high local concentrations of the drug at the site of action with concomitant slow release of the drug from carriers in the blood compartment that results in antivascular effects, similar to that achieved when dosing frequently at low levels. Although this dual mechanism of activity may be linked to other lipid nanoparticle formulations of anticancer drugs, this article summarizes the evidence supporting direct (cytotoxic) and indirect (antivascular) actions of a liposomal formulation of irinotecan. PMID- 22077468 TI - New variant of unclassified congenital dyserythropoietic anaemia: the concept of the erythroid regulator? PMID- 22077469 TI - Neuromonitoring. PMID- 22077470 TI - Laminectomy, durotomy, and piotomy effects on spinal cord intramedullary pressure in severe cervical and thoracic kyphotic deformity: a cadaveric study. AB - OBJECT: Previous studies have shown that cervical and thoracic kyphotic deformity increases spinal cord intramedullary pressure (IMP). Using a cadaveric model, the authors investigated whether posterior decompression can adequately decrease elevated IMP in severe cervical and thoracic kyphotic deformities. METHODS: Using an established cadaveric model, a kyphotic deformity was created in 16 fresh human cadavers (8 cervical and 8 thoracic). A single-level rostral laminotomy and durotomy were performed to place intraparenchymal pressure monitors in the spinal cord at C-2, C4-5, and C-7 in the cervical study group and at T4-5, T7-8, and T11 12 in the thoracic study group. Intramedullary pressure was recorded at maximal kyphosis. Posterior laminar, dural, and pial decompressions were performed while IMP was monitored. In 2 additional cadavers (1 cervical and 1 thoracic), a kyphotic deformity was created and then corrected. RESULTS: The creation of the cervical and thoracic kyphotic deformities resulted in significant increases in IMP. The mean increase in cervical and thoracic IMP (change in IMP [DeltaIMP]) for all monitored levels was 37.8 +/- 7.9 and 46.4 +/- 6.4 mm Hg, respectively. After laminectomies were performed, the mean cervical and thoracic IMP was reduced by 22.5% and 18.5%, respectively. After midsagittal durotomies were performed, the mean cervical and thoracic IMP was reduced by 62.8% and 69.9%, respectively. After midsagittal piotomies were performed, the mean cervical and thoracic IMP was reduced by 91.3% and 105.9%, respectively. In 2 cadavers in which a kyphotic deformity was created and then corrected, the DeltaIMP increased with the creation of the deformity and returned to zero at all levels when the deformity was corrected. CONCLUSIONS: In this cadaveric study, laminar decompression reduced DeltaIMP by approximately 15%-25%, while correction of the kyphotic deformity returned DeltaIMP to zero. This study helps explain the pathophysiology of myelopathy in kyphotic deformity and the failure of laminectomy alone for cervical and thoracic kyphotic deformities with myelopathy. In addition, the study emphasizes the need for correction of deformity during operative treatment of kyphotic deformity, the need for maintaining adequate intraoperative blood pressure during operative treatment, and the higher risk of spinal cord injury associated with operative treatment of kyphotic deformity. PMID- 22077471 TI - Percutaneous vertebroplasty. PMID- 22077472 TI - Cervical decompression and reconstruction without intraoperative neurophysiological monitoring. AB - OBJECT: The primary goal of this study was to review the immediate postoperative neurological function in patients surgically treated for symptomatic cervical spine disease without intraoperative neurophysiological monitoring. The secondary goal was to assess the economic impact of intraoperative monitoring (IOM) in this patient population. METHODS: This study is a retrospective review of 720 consecutively treated patients who underwent cervical spine procedures. The patients were identified and the data were collected by individuals who were not involved in their care. RESULTS: A total of 1534 cervical spine levels were treated in 720 patients using anterior, posterior, and combined (360 degrees ) approaches. Myelopathy was present preoperatively in 308 patients. There were 185 patients with increased signal intensity within the spinal cord on preoperative T2-weighted MR images, of whom 43 patients had no clinical evidence of myelopathy. Three patients (0.4%) exhibited a new neurological deficit postoperatively. Of these patients, 1 had a preoperative diagnosis of radiculopathy, while the other 2 were treated for myelopathy. The new postoperative deficits completely resolved in all 3 patients and did not require additional treatment. The Current Procedural Terminology (CPT) codes for IOM during cervical decompression include 95925 and 95926 for somatosensory evoked potential monitoring of the upper and lower extremities, respectively, as well as 95928 and 95929 for motor evoked potential monitoring of the upper and lower extremities. In addition to the charge for the baseline [monitoring] study, patients are charged hourly for ongoing electrophysiology testing and monitoring using the CPT code 95920. Based on these codes and assuming an average of 4 hours of monitoring time per surgical case, the savings realized in this group of patients was estimated to be $1,024,754. CONCLUSIONS: With the continuing increase in health care costs, it is our responsibility as providers to minimize expenses when possible. This should be accomplished without compromising the quality of care to patients. This study demonstrates that decompression and reconstruction for symptomatic cervical spine disease without IOM may reduce the cost of treatment without adversely impacting patient safety. PMID- 22077473 TI - Examination of the influence of ossification of the anterior longitudinal ligament on symptom progression and surgical outcome of ossification of the thoracic ligamentum flavum: a multicenter study. AB - OBJECT: The purpose of this study was to provide the first evidence for the influence of an ossified anterior longitudinal ligament (OALL) on the clinical features and surgical outcomes in an ossified ligamentum flavum (OLF) in the thoracic region. METHODS: Sixty-three patients who underwent surgery for a 1 level thoracic OLF were identified, and preoperative symptoms, severity of symptoms and myelopathy, disease duration, MR imaging and CT findings, surgical procedure, intraoperative findings, complications, and postoperative recovery were investigated in these patients. Entities of OALLs were found on sagittal CT images to be adjacent to or at the same vertebral level as the OLF were classified into 4 types: no discernible type (Type N), one-sided (Type O), discontinuous (Type D), and continuous (Type C). RESULTS: The duration of symptoms was especially long for Types D and C OALLs. Patients with Type D OALLs had a significantly worse percentage of recovery, as well as worse preoperative JOA scores. CONCLUSIONS: The authors' results showed that a Type D OALL had strong associations with preoperative severity of symptoms and surgical outcomes. These findings may allow surgeons to determine the severity of preoperative symptoms and the probable surgical outcomes from the OALL classifications. Moreover, surgery with instrumentation for Type D OALLs may produce better surgical outcomes. PMID- 22077474 TI - Briakinumab for the treatment of plaque psoriasis. AB - Psoriasis is a chronic inflammatory skin disorder affecting approximately 2% of individuals worldwide. An improved understanding of the pathogenesis of psoriasis has led to the development of targeted biologic therapies. Briakinumab (ABT-874) is a recombinant human antibody that blocks the biological activity of the cytokines interleukin (IL)-12 and IL-23 through their shared subunit p40. IL-12 and IL-23 are key mediators in T-cell differentiation and have been shown to play a significant role in maintaining inflammation and abnormal keratinocyte function in psoriasis patients through development and stimulation of Th1 and Th17 subsets, respectively. In one phase II and four phase III studies (including two 52-week trials), the Psoriasis Area and Severity Index (PASI)-75 score at weeks 12 and 52 was achieved by at least 80.6% and 66.2% (p < 0.001) of patients receiving more than one dose of briakinumab every 4 weeks, respectively, with high proportions of patients achieving PASI-90 and PASI-100 scores (at least 55.4% and 28.8%, respectively; p < 0.001). These studies indicate safety and tolerance of briakinumab therapy for patients with moderate-to-severe chronic plaque psoriasis. In one clinical trial, therapy was associated with increased incidence of major cardiac events. Available results from two briakinumab trials show its positive impact on health-related quality of life. However, the manufacturer has now withdrawn the application in the EU and US. PMID- 22077476 TI - The veterinary quarterly: Changing to a review journal on animal diseases. PMID- 22077475 TI - Effect of stressful life events on the onset and duration of recurrent aphthous stomatitis. AB - BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common and painful oral mucosal disease. Possible etiologies include genetics, vitamin deficiencies, trauma, immune dysfunction, and stress. The goal of this study was to examine the relationship between the occurrence, type, and magnitude of stressful events and the onset and duration of RAS episodes. METHODS: One hundred and sixty subjects with a history of RAS completed a weekly phone survey for up to 1 year, providing data on the occurrence of RAS episodes and details of any stressful events they experienced during the previous week. During RAS episodes, subjects also completed daily paper diaries that recorded incidence and duration of the RAS episode. Stressful events were quantified using the validated Recent Life Changes Questionnaire (RLCQ) and were classified as mental or physical stressors. RESULTS: Stressful life events were significantly associated with the onset of RAS episodes (P < 0.001), however, not with the duration of the RAS episodes. Experiencing a stressful life event increased the odds of an RAS episode by almost three times (OR = 2.72; 95% CI = 2.04-3.62). When controlled for each other, mental stressors had a larger effect (OR = 3.46, 95% CI = 2.54-4.72) than physical stressors (OR = 1.44; 95% CI = 1.04-1.99) on the occurrence of RAS episodes. RAS episodes did not occur more frequently or last longer with increasing stress severity. CONCLUSIONS: In patients with a history of RAS, stressful events may mediate changes involved in the initiation of new RAS episodes. Mental stressors are more strongly associated with RAS episodes than physical stressors. PMID- 22077478 TI - Case of recurrent Sweet's syndrome in a patient with relapsing polychondritis and myelodysplastic syndrome. PMID- 22077479 TI - Retinoids and retinoid-metabolic gene expression in mouse adipose tissues. AB - Vitamin A and its analogs (retinoids) regulate adipocyte differentiation. Recent investigations have demonstrated a relationship among retinoids, retinoid-binding protein 4 (RBP4) synthesized in adipose tissues, and insulin-resistance status. In this study, we measured retinoid levels and analyzed the expression of retinoid homeostatic genes associated with retinol uptake, esterification, oxidation, and catabolism in subcutaneous (Sc) and visceral (Vis) mouse fat tissues. Both Sc and Vis depots were found to contain similar levels of all-trans retinol. A metabolite of retinol with characteristic ultraviolet absorption maxima for 9-cis retinol was observed in these 2 adipose depots, and its level was 2-fold higher in Sc than in Vis tissues. Vis adipose tissue expressed significantly higher levels of RBP4, CRBP1 (intracellular retinol-binding protein 1), RDH10 (retinol dehydrogenase), as well as CYP26A1 and B1 (retinoic acid (RA) hydroxylases). No differences in STRA6 (RBP4 receptor), LRAT (retinol esterification), CRABP1 and 2 (intracellular RA-binding proteins), and RALDH1 (retinal dehydrogenase) mRNA expressions were discerned in both fat depots. RALDH1 was identified as the only RALDH expressed in both Sc and Vis adipose tissues. These results indicate that Vis is more actively involved in retinoid metabolism than Sc adipose tissue. PMID- 22077480 TI - Gemcitabine-loaded innovative nanocarriers vs GEMZAR: biodistribution, pharmacokinetic features and in vivo antitumor activity. AB - INTRODUCTION: Gemcitabine, an anticancer drug, is a nucleoside analog deoxycytidine antimetabolite, which acts against a wide range of solid tumors. The limitation of gemcitabine is its rapid inactivation by the deoxycytidine deaminase enzyme following its in vivo administration. AREAS COVERED: One of the most promising new approaches for improving the biopharmaceutical properties of gemcitabine is the use of innovative drug delivery devices. This review explains the current status of gemcitabine drug delivery, which has been under development over the past 5 years, with particular emphasis on liposomal delivery. In addition, the use of novel supramolecular vesicular aggregates (SVAs), polymeric nanoparticles and squalenoylation were treated as interesting innovative approaches for the administration of the nucleoside analog. EXPERT OPINION: Different colloidal systems containing gemcitabine have been realized, with the aim of providing important potential advancements through traditional ways of therapy. A possible future commercialization of modified gemcitabine is desirable, as was true in the case of liposomal doxorubicin (Doxil((r)), Caely((r))). PMID- 22077481 TI - Template-assisted assembly: scanning tunneling microscopy study of solvent dependent adlattices of alkyl-derivatized tetrathiafulvalene. AB - The self-assembly of an adsorbate as a function of the strength of solvent substrate adsorption is an important yet relatively unexplored subject. In this study, how the strength of solvent-substrate adsorption and solvent-solvent attraction affects the assembly of tetrakis(octadecylthio)tetrathiafulvalene (1) is scrutinized by scanning tunneling microscopy (STM). For solvents with strong intermolecular interactions and adsorption onto graphite, such as long n-alkanes (C(n)H(2n+2), n >= 13), STM reveals that the solvent molecules form lamellae which become a template to direct the assembly of 1 into one-dimensional arrays. The lengths of one of the unit cell vectors for the assemblies are increased and well correlated with the solvent sizes. In situ STM monitoring of 1 introduced onto graphite with preadsorbed n-tetradecane adlattices shows that the developed assemblies of 1 have striped features aligned parallel to the underlying template. In contrast, for solvents with weak adsorption, such as short n-alkanes (C(n)H(2n+2), n <= 12), toluene, and 1,2,4-trichlorobenzene, the adlattice structures of 1 are solvent-independent. PMID- 22077483 TI - Medical and interventional management of patients with severe thrombocytopenia undergoing percutaneous coronary intervention. PMID- 22077482 TI - Effect of oral phytoestrogen on androgenicity and insulin sensitivity in postmenopausal women. AB - AIM: The aim of this study was to determine and compare the effect of treatment with transdermal oestrogen and phytoestrogen on insulin sensitivity and sex hormone-binding globulin (SHBG) levels in healthy postmenopausal women. METHODS: Forty-three healthy postmenopausal women aged 68 +/- 7 (mean +/- SD) years who were not receiving hormonal replacement therapy completed a 3 month randomized drug therapy study. The participants were randomized to one of four groups: 0.05 mg or 0.1 mg transdermal oestrogen/day, or 40 or 80 mg oral phytoestrogen (Promensil)/day insulin sensitivity was indirectly measured using the quantitative insulin sensitivity check index (QUICKI). SHBG, total testosterone, oestradiol, and fasting glucose and insulin levels for calculation of insulin sensitivity were obtained at baseline and at monthly intervals during the 3 months of therapy. RESULTS: In healthy nondiabetic postmenopausal women, the rate of change in QUICKI was significantly different between the red clover based phytoestrogen and transdermal oestrogen groups, so that after three months of therapy, QUICKI with red clover based phytoestrogen therapy was lower than that in the transdermal oestrogen group, p = 0.01. Red clover based phytoestrogen therapy was not associated with any changes in SHBG levels whereas transdermal estrogen therapy significantly increased SHBG levels, p = 0.05. CONCLUSIONS: In contrast to transdermal oestrogen therapy, oral phytoestrogen therapy does not decrease androgenicity and is associated with a decrease in insulin sensitivity. These effects are similar to those of raloxifene and consistent with phytoestrogen's selective oestrogen receptor modulator properties. PMID- 22077484 TI - Predicting the potential demographic impact of predators on their prey: a comparative analysis of two carnivore-ungulate systems in Scandinavia. AB - 1. Understanding the role of predation in shaping the dynamics of animal communities is a fundamental issue in ecological research. Nevertheless, the complex nature of predator-prey interactions often prevents researchers from modelling them explicitly. 2. By using periodic Leslie-Usher matrices and a simulation approach together with parameters obtained from long-term field projects, we reconstructed the underlying mechanisms of predator-prey demographic interactions and compared the dynamics of the roe deer-red fox-Eurasian lynx human harvest system with those of the moose-brown bear-gray wolf-human harvest system in the boreal forest ecosystem of the southern Scandinavian Peninsula. 3. The functional relationship of both roe deer and moose lambda to changes in predation rates from the four predators was remarkably different. Lynx had the strongest impact among the four predators, whereas predation rates by wolves, red foxes, or brown bears generated minor variations in prey population lambda. Elasticity values of lynx, wolf, fox and bear predation rates were -0.157, 0.056, -0.031 and -0.006, respectively, but varied with both predator and prey densities. 4. Differences in predation impact were only partially related to differences in kill or predation rates, but were rather a result of different distribution of predation events among prey age classes. Therefore, the age composition of killed individuals emerged as the main underlying factor determining the overall per capita impact of predation. 5. Our results confirm the complex nature of predator-prey interactions in large terrestrial mammals, by showing that different carnivores preying on the same prey species can exert a dramatically different demographic impact, even in the same ecological context, as a direct consequence of their predation patterns. Similar applications of this analytical framework in other geographical and ecological contexts are needed, but a more general evaluation of the subject is also required, aimed to assess, on a broader systematic and ecological range, what specific traits of a carnivore are most related to its potential impact on prey species. PMID- 22077485 TI - Recovery rates of bluetongue virus serotypes 1, 2, 4 and 8 Spanish strains from orally infected Culicoides imicola in South Africa. AB - Bluetongue (BT) is an infectious disease of ruminants that has spread northwards in Europe during the last decade. The aetiological agent of the disease is an arbovirus [bluetongue virus (BTV)] that belongs to the genus Orbivirus (family Reoviridae). The virus is transmitted by certain species of biting midge within the genus Culicoides (Diptera: Ceratopogonidae). Information on the vector status of the Culicoides species in a specific area will be essential to predict the risk for BTV incursion. Field-collected Culicoides (Avaritia) imicola Kieffer from South Africa were fed on blood containing several Spanish isolates of BTV. Despite the high virus concentrations in the bloodmeal (5.1-6.4 log(10) TCID(50) /mL of blood), virus was recovered from <1% of midges assayed after incubation. Virus concentrations >2.5 log(10) TCID(50) /midge in individual infected C. imicola suggest virus replication with possible risk for transmission to susceptible vertebrate hosts in the field for at least two of the serotypes assayed (BTV-1 and BTV-2). A third serotype (BTV-4) was very close to the estimated threshold for transmission. The relatively low to near refractory status of C. imicola compared with other vector species such as Culicoides bolitinos supports previous results, indicating that Culicoides species other than C. imicola may play a more important role in the epidemiology of BTV. PMID- 22077486 TI - Spiradenocarcinoma with low-grade basal cell adenocarcinoma pattern: report of a case with varied morphology and wild type TP53. AB - We present a patient with a 2-cm spiradenocarcinoma of the left arm resembling low-grade salivary gland basal cell adenocarcinoma. In addition to showing attributes of conventional spiradenoma, the benign component showed prominent areas of cystic change with focal apocrine differentiation, glands with and without mucinous differentiation, clear cell change and focal adenoid cystic carcinoma-like areas. The malignant component was composed of nodules of basaloid cells arranged in sheets with variable tendency to luminal differentiation. The nuclear atypia was low-grade, and the mitotic index was high in the malignant component (to 8/10 high power fields). Immunohistochemically, there was diffuse but variable positivity for cytokeratin 7 in both the benign and malignant components. Epithelial membrane antigen was focally positive, highlighting cells with ductal (luminal) differentiation. Expression of p63 was observed in 50 and 80% of the cells in the benign and malignant components, respectively. Calponin was negative. The proliferative index (MIB-1/Ki-67) was <3% in the benign component and up to 10% in the malignant component. Although the malignant component displayed patchy areas with nuclear p53 immunoreactivity with variable intensity, no mutation in the TP53 gene was identified. PMID- 22077487 TI - T-cell activation genes differentially expressed at birth in CD4+ T-cells from children who develop IgE food allergy. AB - BACKGROUND: Presymptomatic immaturity in neonatal T-cell function is a consistent antecedent of allergic disease, including reduced responsiveness to polyclonal activation. METHODS: To elucidate the underlying mechanisms, we examined for differences in T-cell gene expression in longitudinal samples collected at birth and at 1 year of age in children with (n = 30) and without IgE-mediated food allergy (n = 30). We employed a low-level soluble anti-CD3 stimulus to activate the T-cell receptor (TCR) and surveyed gene expression by DNA microarray in purified CD4(+) T-cells. Allergen-specific responses were assessed in parallel functional studies. RESULTS: At birth, the allergic group showed a reduced number of genes up regulated in response to anti-CD3 treatment on the microarray and a reduced lympho proliferative capacity, suggesting clear differences in T-cell signalling pathways. Polymerase chain reaction (PCR) validation of candidate genes confirmed significantly lower expression of a number of genes in the allergic group including RELB, NFKB2, LIF and FAS. By 12 months of age, there were marked changes in the anti-CD3 response in all infants, culminating in upregulation of cytokine genes (IL-5, IL-13, IL-17 and IL-22). Neonatal differences were no longer apparent. Instead, the allergic group, all symptomatic by this age, showed differential expression of T-cell lineage pathways including GATA-3, MAL and FcER1 in unstimulated T-cells. Allergen stimulation induced significantly higher cytokines production (IL-5, IL-13 and IFNgamma) in the allergic group. CONCLUSION: Although transient, suboptimal neonatal T-cell activation pathways that signal through the NF-kappaB complex may affect the developmental transition of T-cell phenotypes in the periphery shortly after birth and may increase the risk of food allergy. PMID- 22077488 TI - Prophylactic effect of topical fluoroquinolones in a rabbit model of Staphylococcus aureus endophthalmitis. AB - PURPOSE: To evaluate the prophylactic effects of topical gemifloxacin, pazufloxacin, moxifloxacin, and levofloxacin for experimental Staphylococcus aureus endophthalmitis in a rabbit model. METHODS: Rabbits were randomly divided into 5 groups with 14 rabbits each. The control group received balanced salt solution (BSS); the other 4 groups received 1 drop of gemifloxacin, pazufloxacin, moxifloxacin, or levofloxacin ophthalmic solution, respectively, in the left eye at each of the following time points: 60, 45, 30, and 15 min before infection, immediately after infection, and then 6, 12, 18, and 24 h postinfection. S. aureus ATCC25923 [5*10(5) colony-forming units (CFUs) in 50 MUL] was injected into the aqueous humor of each eye, and the clinical severity of the eyes was assessed 24 h postinfection. Two random eyeballs from each group were collected for histopathologic observation. Aqueous and vitreous samples of 12 other eyes were collected, diluted, and plated to determine the number of recovered CFUs. RESULTS: Fluoroquinolone-treated eyes had significantly lower clinical scores and lower numbers of bacteria recovered from the aqueous humor than the BSS control group eyes. There was no difference, however, among the 4 fluoroquinolone-treated groups. In contrast, none of the fluoroquinolones reduced the number of bacteria recovered (CFUs) from the vitreous humor. In terms of the histopathologic results, less severe inflammation and relatively well-preserved ocular architecture were observed in fluoroquinolone-treated eyes, when compared with the control group. CONCLUSIONS: Gemifloxacin and pazufloxacin may be as effective as moxifloxacin and levofloxacin for topical prophylaxis and for the treatment of S. aureus-induced endophthalmitis in the rabbit model. PMID- 22077490 TI - Resonance Raman intensity analysis of the A band short-time photochemical dynamics of 4,5-ethylenedithio-1,3-dithiole-2-thione. AB - Resonance Raman spectra (RRs) for 4,5-ethylenedithio-1,3-dithiole-2-thione (EDDT) were obtained with 397.9 and 416 nm excitation wavelengths, and density functional calculations were performed to elucidate the electronic transitions and the RRs of EDDT in chloroform solvent. The RRs indicate that the Franck Condon region photodynamics have multidimensional character with nuclear motion predominantly along the C(4)?C(5) stretch and the C(4)?C(5) twist out-of-plane. Resonance Raman cross-sections of A-band absorption have been obtained for the vibrational modes of EDDT with its excitation frequencies spanning the 408 nm. Resonance Raman intensity analysis of the resulting RRs excitation profiles and absorption spectrum using a time-dependent wave packet formalism yields mode specific nuclear displacement and vibrational reorganizational energies. The intensity analysis results for EDDT were compared to previously reported results for dimethyl 1,3-dithiole-2-thione-4,5-dicarboxylate (DDTD), which shows that the additional six-member heterocycle of EDDT strongly affects the reorganizational energy and energy participation. The authors briefly discuss the differences and similarities of the spectra in terms of molecular symmetry and electron density. PMID- 22077489 TI - Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. AB - Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (*OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of *OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing *OH in irradiated tissue with no side effects. PMID- 22077491 TI - Orthogonal test design for optimisation of extraction of trans-resveratrol from Pinot Noir-grape pomace. AB - Yield of trans-resveratrol from Pinot Noir-grape pomace obtained by microwave assisted extraction (MAE) through an orthogonal experiment (16 (4(4))) was investigated to get the best extraction conditions. In this method, the highest yield was obtained when the extraction solvent used ethanol; the ratio of raw material to solvent, the extraction time, the extraction temperature and microwave irradiation power were 1:20 (g mL(-1)), 30 min, 55 degrees C and 1.0 kW, respectively. The average yield of trans-resveratrol was 90.87%, and the recovery was in the range of 85.49-89.04% with relative standard deviation lower than 1.39%. Then, the extract of MAE was separated by NKA-9 macroporous resin and re-crystallisation. Finally, the purity of trans-resveratrol was 97.47%. PMID- 22077492 TI - Attitudinal and demographic determinants of diet quality and implications for policy targeting. AB - BACKGROUND: Poor diet quality is a major public health concern that has prompted governments to introduce a range of measures to promote healthy eating. For these measures to be effective, they should target segments of the population with messages relevant to their needs, aspirations and circumstances. The present study investigates the extent to which attitudes and constraints influence healthy eating, as well as how these vary by demographic characteristics of the UK population. It further considers how such information may be used in segmented diet and health policy messages. METHODS: A survey of 250 UK adults elicited information on conformity to dietary guidelines, attitudes towards healthy eating, constraints to healthy eating and demographic characteristics. Ordered logit regressions were estimated to determine the importance of attitudes and constraints in determining how closely respondents follow healthy eating guidelines. Further regressions explored the demographic characteristics associated with the attitudinal and constraint variables. RESULTS: People who attach high importance to their own health and appearance eat more healthily than those who do not. Risk-averse people and those able to resist temptation also eat more healthily. Shortage of time is considered an important barrier to healthy eating, although the cost of a healthy diet is not. These variables are associated with a number of demographic characteristics of the population; for example, young adults are more motivated to eat healthily by concerns over their appearance than their health. CONCLUSIONS: The approach employed in the present study could be used to inform future healthy eating campaigns. For example, messages to encourage the young to eat more healthily could focus on the impact of diets on their appearance rather than health. PMID- 22077493 TI - Appearance of anatomical structures of mandible on panoramic radiographs in Iranian population. AB - PURPOSE: Currently panoramic radiography is used for diagnosis of dental and bone lesions, but anatomical structures also can be seen and may be useful in dental managements. This study aimed to investigate the visibility of some important mandibular features relating to neurovascular structures in Iranian population. MATERIALS AND METHODS: Panoramic radiographs were taken by Planmeca machine from 412 patients using standard exposure. The position of patient was in compliance with standard protocol. Then mandibular incisive canal was evaluated and data were analyzed statistically. RESULTS: Mental foramen, anterior loop of mental nerve and incisive canal could be observed in 84.2, 66 and 51.7% of the cases. Respectively, lingual foramen was observed in only 6.1% of the radiographs. Gender doesn't affect on the visibility of these structures. There was a relationship between mandibular foramen and canal with age. CONCLUSION: Mandibular incisive canal was considered in 51.7% of cases, it was observed that the result obtained was more than those of other researches. PMID- 22077495 TI - Reviews on animal diseases recently published in other journals. PMID- 22077494 TI - Factors associated with a drive for muscularity among gay and bisexual men. AB - Among gay and bisexual men, body dissatisfaction can manifest itself in the form of a desire for increased muscularity. Possibly in response to homophobia, the socio-sexual culture of gay and bisexual men privileges muscularity and may help to perpetuate a sense of body dissatisfaction. Little is known about factors associated with a drive for muscularity among gay and bisexual men. This study recruited participants (n = 400) at Toronto's 2008 lesbian, gay, bisexual and transgender festival to provide data used to examine the relationship between a drive for muscularity and demographics (age, race, education, HIV status), psychological factors (depression, disordered eating, internalised homophobia, substance use), body mass, a history of childhood sexual abuse and sexual risk. Multivariate analyses revealed that a drive for muscularity was associated with age, disordered eating, depression, sexual risk and internalised homonegativity. These findings can be used to advance the health and wellbeing of gay and bisexual men, particularly interventions designed to mitigate the effects of internalised homonegativity and policies aimed at reducing homophobia. PMID- 22077497 TI - Fundamental approaches to nonadiabaticity: toward a chemical theory beyond the Born-Oppenheimer paradigm. PMID- 22077498 TI - Increased natural killer cells and decreased CD3(+)CD8(+)CD62L(+) T cells in CML patients who sustained complete molecular remission after discontinuation of imatinib. PMID- 22077499 TI - Primary cutaneous nocardiosis caused by Nocardia beijingensis in an immunocompromised patient with chemotherapy for advanced prostate cancer. PMID- 22077501 TI - Patient follow-up and monitoring medicines. PMID- 22077503 TI - Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study. AB - BACKGROUND: Data on the frequency and relative risk (RR) of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours receiving chemotherapy in clinical practice are limited. OBJECTIVE: The aim of the study was to estimate the frequency and RR of thrombocytopenia in adult patients with solid tumours receiving chemotherapy treatment. METHODS: For this retrospective, hospital-based study, adult patients with solid tumours who received chemotherapy at the University Medical Center Utrecht in the period 2004-6 were identified from the Utrecht Patient Oriented Database. We examined the frequency of (i) overall thrombocytopenia (defined as platelet count <100 * 109/L) with or without other cytopenias; (ii) isolated thrombocytopenia (i.e. without other cytopenias); and (iii) the frequency and RR of overall thrombocytopenia and isolated thrombocytopenia associated with different cytotoxic agents. RESULTS: A total of 614 patients receiving one of 37 different chemotherapy regimens was included. Overall thrombocytopenia frequency was 21.8% and isolated thrombocytopenia frequency was 6.2%. The highest frequencies of thrombocytopenia were observed in patients receiving carboplatin monotherapy (81.8%) and combination therapies that included carboplatin (58.2%), gemcitabine (64.4%) or paclitaxel (59.3%). The highest RRs of thrombocytopenia, compared with cisplatin-based therapy, were observed for combination therapies of carboplatin/gemcitabine (RR 10.1; 95% CI 5.5, 18.5) and carboplatin/paclitaxel/etoposide (RR 11.8; 95% CI 6.7, 20.8). In 54% of cases, the thrombocytopenia was of grade 2-4, which are considered to be the most clinically relevant grades. The highest frequencies of isolated thrombocytopenia were found with combination therapies that included oxaliplatin (28.6%) or gemcitabine (28.9%). CONCLUSIONS: The results suggest that CIT is a relevant problem in clinical practice. Further research is necessary to investigate the clinical consequences of thrombocytopenia. The observed frequencies of thrombocytopenia were lower than those observed in older studies, but comparable with that observed in a recent US-based study. The observed increased risks for possible immune-mediated thrombocytopenia associated with exposure to oxaliplatin and gemcitabine contribute to the suspicion that these drugs can cause immune-mediated thrombocytopenia, and warrant further investigation. For clinicians, the mechanism has important consequences because in immune-mediated thrombocytopenia the drug must be avoided, while in dose dependent thrombocytopenia a dose reduction may be sufficient. PMID- 22077502 TI - Putting the cardiovascular safety of aromatase inhibitors in patients with early breast cancer into perspective: a systematic review of the literature. AB - In the adjuvant setting, the third-generation aromatase inhibitors (AIs) anastrozole, letrozole and exemestane are recommended at some point during treatment, either in the upfront, switch after tamoxifen or extended treatment setting after tamoxifen in postmenopausal patients with hormone receptor-positive early breast cancer. AIs have demonstrated superior disease-free survival and overall benefit-to-risk profiles compared with tamoxifen. Potential adverse events, including cardiovascular (CV) side effects, should be considered in the long-term management of patients undergoing treatment with AIs. AIs reduce estrogen levels by inhibiting the aromatase enzyme, thus reducing the levels of circulating estrogen. This further reduction in estrogen levels may potentially increase the risk of developing CV disease. This systematic review evaluated published clinical data for changes in plasma lipoproteins and ischaemic CV events during adjuvant therapy with AIs in patients with hormone receptor positive early breast cancer. The electronic databases MEDLINE, EMBASE, Derwent Drug File and BIOSIS were searched to identify English-language articles published from January 1998 to 15 April 2011 that reported data on AIs and plasma lipoproteins and/or ischaemic CV events. Overall, available data did not show any definitive patterns or suggest an unfavourable effect of AIs on plasma lipoproteins from baseline to follow-up assessment in patients with hormone receptor-positive early breast cancer. Changes that occurred in plasma lipoproteins were observed soon after initiation of AI therapy and generally remained stable throughout the studies. Available data do not support a substantial risk of ischaemic CV events associated with adjuvant AI therapy; however, studies with longer follow-up are required to better characterize the CV profile of AIs. PMID- 22077504 TI - Serotonin reuptake inhibitors and hyperprolactinaemia: a case/non-case study in the French pharmacovigilance database. AB - BACKGROUND: Hyperprolactinaemia is a common endocrinological disorder that can be caused by a variety of physiological and pathological conditions, although in a large proportion of cases hyperprolactinaemia is drug-induced. Serotonin reuptake inhibitors (SRIs) are reportedly associated with hyperprolactinaemia; however, the number of published cases in the literature is limited. OBJECTIVE: The aim of the study was to investigate the association between exposure to SRIs and the risk of reporting of hyperprolactinaemia in a spontaneous reporting database. METHODS: All cases of adverse drug reactions (ADRs) involving hyperprolactinaemia spontaneously reported to the French Pharmacovigilance Database from 1985 to December 2009 were reviewed. Cases of hyperprolactinaemia in SRI users were described. In a case/non-case analysis, the association between reported cases of hyperprolactinaemia and the use of SRIs was assessed by calculating reporting odds ratios (ROR) with their 95% confidence intervals (CIs). RESULTS: A total of 11 863 reports with SRIs were collected, of which 187 reported hyperprolactinaemia ADRs. Subjects were 39.7 +/- 13.5 years of age on average and mainly female (71%). We observed an increased risk of reporting of hyperprolactinaemia with the use of SRIs as antidepressants (overall ROR 3.3; 95% CI 2.8, 3.8), particularly with fluvoxamine (ROR 4.5; 95% CI 2.8, 7.2), citalopram (ROR 3.9; 95% CI 2.6, 5.8), fluoxetine (ROR 3.6; 95% CI 2.8, 4.7) and paroxetine (ROR 3.1; 95% CI 2.3, 4.2). Duloxetine, milnacipran and sertraline were not associated with an increased risk of reporting of hyperprolactinaemia. CONCLUSIONS: Treatment with SRIs is associated with an increased risk of reported hyperprolactinaemia. When investigating the aetiology of diagnosed hyperprolactinaemia, physicians should systematically enquire about treatment with SRIs. The risk of hyperprolactinaemia should be mentioned in the labelling of all SRI compounds. PMID- 22077505 TI - Pharmacogenetic risk for adverse reactions to irinotecan in the major ethnic populations of Singapore: regulatory evaluation by the health sciences authority. AB - BACKGROUND: For genetic polymorphisms known to alter drug effect or safety, regulatory authorities can tap into population genomic databases and other sources of allele and genotype distribution data to make a more informed decision about the anticipated impact of such variants on the main ethnic groups in a country's population. OBJECTIVE: The aim of this short communication is to describe how the Singapore Health Sciences Authority (HSA) made use of allele and genotype distributions in the main ethnic groups in Singapore (Chinese, Malay, Indian) and population genetic tools to compare with North American Caucasians and Japanese. METHODS: Published papers and publicly accessible genomic databases were searched up to August 2009 to obtain allele and genotype frequencies for UGT1A1*6 and *28, two common variants of UGT1A1, a gene that encodes for a key enzyme in the pathway of irinotecan metabolism. These variants are associated with greater risk of serious toxicity. RESULTS: In Singapore, the combined prevalence of three high-risk genotypes, UGT1A1*6/*6, *6/*28 and *28/*28, is 9.7% in Chinese, 5.0% in Malays and 18.7% in Indians, compared with 11.5% in North American Caucasians and 8.1% in Japanese. Indians are at an elevated risk of irinotecan-induced neutropenia associated with UGT1A1*28 compared with Chinese and Japanese, and at an even higher risk compared with North American Caucasians. On the other hand, Chinese and Japanese are at an elevated risk of irinotecan induced neutropenia associated with UGT1A1*6 relative to Indians in Singapore or North American Caucasians. Population genotype data were the basis for the HSA to request revision of the package insert from manufacturers of irinotecan products. Moreover, the data provided the impetus for the HSA to publicize the availability of UGT1A1 genetic testing at the National Cancer Centre. CONCLUSION: With the growing volume of genomic data and pharmacogenomic associations, a regulatory authority is now able to more readily utilize population genetic information and tools to supplement evaluations of drug products pertinent to the country's ethnic demography. PMID- 22077506 TI - Examining the utilization and tolerability of the non-sedating antihistamine levocetirizine in England using prescription-event monitoring data. AB - BACKGROUND: Levocetirizine was launched onto the UK market in September 2001. It is indicated for symptomatic treatment of allergic rhinitis (AR), including persistent AR and chronic idiopathic urticaria. OBJECTIVE: The aim of the study was to monitor the safety of levocetirizine prescribed in the primary care setting in England, in the immediate postmarketing period. METHODS: Exposure data were derived from dispensed prescriptions written by primary care physicians (general practitioners [GPs]) for levocetirizine (November 2001-November 2002): patient demographic, indication, pattern of use and outcome (event) data from enhanced prescription-event monitoring (PEM) questionnaires (with additional questions to gather further relevant information) returned by GPs. Incidence density observation rates (IDobs) [number of first reports/1000 patient-months] between months 1 and 2 (IDobs(m1/m2)) were compared for the whole cohort and by groups defined by indication and pattern of use. RESULTS: The cohort comprised 12 367 patients (median age 37 years [interquartile range 22-55]; 58% female). The most frequent indication was AR (67%; n = 8275). After 2 months, 35.7% (n = 2414) of patients were still taking levocetirizine. 'Condition improved' was the most common event and reason for stopping treatment. Headache/migraine was uncommon but associated with starting treatment (IDobs(m1/m2) 2.4 [95% CI 1.1, 6.0]), as was drowsiness/sedation (IDobs(m1/m2) 11.5 [95% CI 4.2, 43.9]). Cardiovascular events occurred rarely or very rarely, as did most central and peripheral nervous system events. No serious adverse drug reactions (ADRs) were reported. Events related to effectiveness were more frequent in month 1 than month 2 for all patient subgroups. CONCLUSIONS: This postmarketing surveillance study shows that levocetirizine is well tolerated when used in general practice in England. No previously unrecognized ADRs were detected. This study highlights how modifications to PEM, such as additional questions, are contributing to the evaluation of drug utilization factors in relation to risks. PMID- 22077507 TI - Comparing adverse event rates of oral blood glucose-lowering drugs reported by patients and healthcare providers: a post-hoc analysis of observational studies published between 1999 and 2011. AB - BACKGROUND: Non-serious symptomatic adverse drug events (ADEs) affect the real benefit-risk ratio of a drug. Currently, such ADEs are quantified in different ways, often using reports from a healthcare provider or patients, resulting in large variations in estimated rates. Several studies showed that patients report bothersome or symptomatic ADEs more frequently than providers, but no comparisons to an external reference or gold standard have been made. OBJECTIVE: We conducted a literature review to assess the agreement and concurrent validity of healthcare provider- and patient-oriented methods for quantifying symptomatic ADEs of oral blood glucose-lowering drugs in patients with type 2 diabetes mellitus. METHODS: We systematically searched MEDLINE and EMBASE databases for observational studies reporting on rates of ADEs in patients treated for type 2 diabetes that were published between 1999 and 2011. We included nine observational studies reporting absolute rates of symptomatic ADEs in patients receiving monotherapy. We calculated 95% confidence intervals and assessed agreement between rates observed with different methods. We assessed concurrent validity using the range noted in the Summary of Product Characteristics (SPC) as the gold standard. RESULTS: A comparison of rates reported by patients and providers was only possible using three studies of metformin that assessed mainly gastrointestinal (GI) ADEs. Provider-oriented methods by means of medical record review gave lower rates for abdominal pain (0.6-3.7%), dyspepsia (1.3-2.8%) and constipation (0.6-1.0%) than a patient questionnaire method (8.5%, 11.9% and 20.7%, respectively). For diarrhoea, the patient-reported rate (5.2%) was in agreement with the provider based rates (1.6-7.6%). The majority of the rates reported by providers and patients were not corresponding with the ranges in the SPC. For GI ADEs the rates were all lower, whereas for lactic acidosis and hypoglycaemia the rates were higher. CONCLUSION: Although it has repeatedly been proposed that patients' reports on safety should be incorporated with providers' reports, especially for symptomatic ADEs, the number of observational studies using patient-oriented methods for assessing ADEs other than hypoglycaemia are limited. Provider-based measurement tended to underestimate symptomatic ADEs. Patient-oriented methods seemed to give ADE rates that were closer to the rates reported in the SPC. PMID- 22077508 TI - Modified prescription-event monitoring studies: a tool for pharmacovigilance and risk management. AB - Prescription-Event Monitoring (PEM) is a well established postmarketing surveillance technique designed to monitor the overall safety of newly marketed medicines as used in real-life clinical practice, usually in cohorts of at least 10 000 patients. At the Drug Safety Research Unit in the UK we are now moving towards a more targeted safety surveillance known as Modified PEM (M-PEM). These studies combine the advantages of conventional PEM studies (in monitoring general safety and identification of unexpected risks of a medicine) with that of a more targeted safety study that addresses specific questions (to better understand known or partially known risks with a medicine). Through the use of enhanced data collection questionnaires, M-PEM expands the range of applications of conventional PEM, which include more detailed characterization of real-life drug use, adherence to prescribing recommendations and targeted analysis of events requiring special monitoring by regulatory authorities. A particularly useful application is the evaluation of the safety of a medicine in special populations or subgroups (e.g. patients switching from another therapy or patients with a particular risk factor) or following important changes in the product's lifecycle (e.g. a licensing or formulation change). M-PEM studies therefore have an important contribution to make to pharmacovigilance and the risk management of medicines by providing valuable information on the use of new medications under real-life situations. PMID- 22077509 TI - Family planning programmes and action in Western Europe. AB - Abstract Neo-Malthusian organisations for spreading birth control propaganda were created in many West European countries in the 1870s and '80s. But the birth control movement proper, with its provision of clinics and other means of supplying advice on contraception, began much later-generally after World War I and largely on a welfare basis, divorced from Malthusianism. Legal and other difficulties impeded progress and conditioned the nature of the movement. Since World War II, however, the relevance of birth control has come increasingly to be recognized and the movement has expanded markedly. In some countries - especially in France, West Germany and Italy - there are still legal obstacles, though ways have been found of avoiding them. But even in other countries the direct impact of birth control clinics is far smaller than might have been expected and married couples still obtain their information on contraception from other sources. In recent years the various national movements have shown a greater interest in the evaluation of their activities. As a result, the near future may see substantial changes in their structure and in the approach to their potential clientele. PMID- 22077510 TI - A study of internal migration in England and Wales : Part I. AB - Abstract Statistics ofpersons classified jointly by county of birth and county ofresidence have been published in the England and Wales census volumes since 1851 and the present study draws mainly on these data. A group of persons recorded in a census as natives of county A and residents of county Bare sometimes referred to as lifetime migrants from county A to county B. Statistics of lifetime migrants have often been used in studies of internal migration but these have one great disadvantage. The number of lifetime migrants from A to B does not relate to a specific period of time. It is impossible, for example, in such studies to consider the association between specific migration streams and differential economic activity. An attempt is made in this study to transform lifetime migration data into intercensal migration streams. Some of the results are presented and the most significant migration patterns during the period 1851 1951 are described. PMID- 22077511 TI - Finite approximations in demography. AB - Abstract Conventions exist for carrying out the arithmetic of population projection, finding the intrinsic rate of natural increase, and other demographic calculations. These are good approximations only for populations which are stationary or increasing very slowly. For rapidly increasing populations, which are presently the subject of much study, they can be readily improved. The improved formulae take account of the way in which the increase shifts the distribution of population within the five-year age group. A number of examples are given of the derivation of corrections to existing formulae. While the corrections are smaller than the error of the data available for most countries, such formulae are worth introducing in anticipation of better data. They in no way depend on machine computation, but the computer makes them especially easy to apply. PMID- 22077512 TI - An analytic simulation model of human reproduction with demographic and biological components. AB - Abstract This Monte Carlo model for simulating the reproductive history of a cohort of women is described in detail. The model provides for patterns of survival, sterility, formation and dissolution of sexual unions, fecundability, lactation, foetal wastage, family planning practices etc. Natality indices specific for marital status, for duration of marriage and for age, as well as analyses of birth spacing patterns are among the results that may be obtained. In the model, the experimental unit is an individual woman. The complete life history of a woman is generated and recorded before the history of the next woman is generated. The data for the whole cohort are analyzed at the end of the programme. The model includes two kinds of states into which a woman may pass, namely: (1) permanent changes of status such as death, sterility, or becoming a family planner, and (2) temporary states, each with a probability distribution of length of stay. The probabilities of the various events or changes of state may vary from age, parity, and other features of a woman's status or history. Natural fecundability at any age may also vary from woman to woman. In this programme natality patterns and specific indices such as age-specific fertility rates are produced, in a quasi-realistic fashion, by the interplay of the demographic and biological parameters postulated for any cohort. Consequently, the effect of changes in anyone factor can be studied, as well as the interaction resulting from changes in several factors. The purposes and potentials of the model are both substantive and methodological. As an illustration, a series of computer runs attempting to simulate the reproductive patterns of Indian women is presented. These results, as well as some additional ones, indicate some effects of changes in marital patterns, levels of fecundability, duration of post-partum non-susceptibility, age incidence of sterility and foetal wastage. In the final section of the paper, the advantages and possible applications of the model are discussed together with the limitations encountered to date in the efforts to apply the model. PMID- 22077513 TI - A problem of estimating a contingency table arising in demographic analysis. AB - Abstract This note deals with a special problem of estimating a contingency table arising in demographic analysis. What we require are the estimates of the numbers of births and deaths in Malaya crossclassified by state and race for the years of the Japanese occcupation, 1942-45. For many reasons this period had an adverse effect on the Chinese and Indian Communities, and hence the two-fold result of a greater reduction in the number of births and a larger increase in the number of deaths in states with a smaller proportion of Malay population. The estimates are worked out by means of a technique which takes into consideration this actual demographic situation. PMID- 22077514 TI - Changing population characteristics in Tibet, 1959 to 1965. AB - Abstract This research note records the most recent Chinese figures for the population of Tibet, together with the official explanation for a decline in 1959, compared with the totals announced for 1953 and 1957, followed by a steady increase since 1960. Brief reference is made to political and economic changes which are affecting the composition of population. PMID- 22077515 TI - A note on nursing practices in an American isolate with a high birth rate. AB - Abstract An unusually short interval between successive births in a non contracepting and breast-feeding population has been reported by Dr. Mindel C. Sheps (Pop. Studies, 19, 1). Nursing practices that might affect the interval between birth and pregnancy are reported here from systematic observations made in the field. Probable factors are: (1) a maternal diet high in calories and in protein; (2) although infants are nursed for many months, each nursing period is short in a busy and highly patterned community schedule; and (3) supplementary feeding is introduced at an early age. PMID- 22077519 TI - Unraveling the multiple myeloma genome in the next-generation sequencing era: challenges to translating knowledge into the clinic. PMID- 22077518 TI - Demetalation of Fe, Mn, and Cu chelates and complexes: application to the NMR analysis of micronutrient fertilizers. AB - The application of nuclear magnetic resonance (NMR) for the quality control of fertilizers based on Fe(3+), Mn(2+), and Cu(2+) chelates and complexes is precluded by the strong paramagnetism of metals. Recently, a method based on the use of ferrocyanide has been described to remove iron from commercial iron chelates based on the o,o-EDDHA [ethylenediamine-N,N'bis(2 hydroxyphenylacetic)acid] chelating agent for their analysis and quantification by NMR. The present work extended that procedure to other paramagnetic ions, manganese and copper, and other chelating, EDTA (ethylenediaminetetraacetic acid), IDHA [N-(1,2-dicarboxyethyl)-d,l-aspartic acid], and complexing agents, gluconate and heptagluconate. Results showed that the removal of the paramagnetic ions was complete, allowing us to obtain (1)H NMR spectra characterized by narrow peaks. The quantification of the ligands by NMR and high-performance liquid chromatography showed that their complete recovery was granted. The NMR analysis enabled detection and quantification of unknown impurities without the need of pure compounds as internal standards. PMID- 22077521 TI - Recent advances in hematology: an update from the 16th Congress of the EHA. AB - The burden of hematological disorders on healthcare providers is reaching a new peak as the population continues to age, making current research and debate in hematology arguably of greater importance than ever before. At the 16th Congress of the European Hematology Association in London, UK, the latest advances in research, and their associated clinical implications, were highlighted. This article provides a brief overview of a selection of presentations taken from the extensive program. PMID- 22077522 TI - Stem cells and beyond: report on the 40th Annual Scientific Meeting of the International Society of Experimental Hematology. AB - The 40th Annual Scientific Meeting of the International Society of Experimental Hematology and Stem Cells was held in beautiful Vancouver, Canada, and was chaired by David Scadden, Gerald de Haan and Peter Lansdorp. Topics such as hematopoietic stem cell biology, development, aging, microenvironment, signaling, genomics and transcriptional control in the context of normal and malignant hematopoiesis were addressed by key speakers in the field. PMID- 22077523 TI - Prevalence, risk factors and mortality of pulmonary hypertension defined by right heart catheterization in patients with sickle cell disease. PMID- 22077525 TI - Classification and therapeutic approaches in autoimmune hemolytic anemia: an update. AB - Autoimmune hemolytic anemia (AIHA) is an uncommon autoantibody-mediated immune disorder that affects both children and adults. The diagnosis of AIHA relies mainly on the direct antiglobulin test, which is a highly sensitive and relatively specific test. The classification of AIHA is based on the pattern of the direct antiglobulin test and on the immunochemical properties of the autoantibody (warm or cold type), but also on the presence or absence of an underlying condition or disease (secondary vs primary AIHAs) that may have an impact on treatment and outcome. The distinction between AIHAs due to warm antibody (wAIHA) and AIHAs due to cold antibody is a crucial step of the diagnostic procedure as it influences the therapeutic strategy. Whereas corticosteroids are the cornerstone of treatment in wAIHA, they have no or little efficacy in cold AIHA. In wAIHA that is refractory or dependent to corticosteroids, splenectomy and rituximab are both good alternatives and the benefit?risk ratio of each option must be discussed on an individual basis. In chronic agglutinin disease, the most common variety of cold AIHA in adults, beyond supportive measures, rituximab given either alone or in combination with chemotherapy may be helpful. In this article, the classification of AIHA and the recent progress in therapeutics are discussed. PMID- 22077524 TI - The epidemiology, evaluation and treatment of stroke in adults with sickle cell disease. AB - Stroke is a frequent and severe complication in adults with sickle cell disease. Ischemic stroke often causes physical and cognitive disability, while hemorrhagic stroke has a high mortality rate. As more children survive, the number of strokes in adults is increasing, yet stroke remains poorly understood. We review the epidemiology of ischemic and hemorrhagic stroke in adults with sickle cell disease and outline a practical approach to the evaluation of stroke including both sickle cell disease specific and general risk factors. We discuss the acute treatment and secondary prevention of stroke in this population based on the evidence in children with sickle cell disease and the general population, in addition to the limited studies in adults with sickle cell disease. PMID- 22077526 TI - Late-onset neutropenia following rituximab therapy: incidence, clinical features and possible mechanisms. AB - Late-onset neutropenia (LON) is emerging as a common adverse effect to rituximab therapy owing to widespread use of this drug in the treatment of B-cell lymphomas and autoimmune diseases. However, the true incidence and mechanisms are not fully understood. LON has been reported in 5?27% of rituximab-treated lymphoma patients. Similar figures apply for autoimmune patients but they appear to have more infections during the neutropenic period. Recent reports imply that host factors may play an intriguing role for development of LON, for example, polymorphisms in FCGR3. Pronounced B-lymphocyte depletion and lower serum IgM, as reported in LON patients during the period of neutropenia compared with matched controls, may play a role for understanding the mechanisms and risk stratification for emergence of LON. PMID- 22077527 TI - Splenectomy for hereditary spherocytosis: complete, partial or not at all? AB - Hereditary spherocytosis (HS) is an hematologic disorder, common in the Northern European population, which is characterized by hemolytic anemia and splenomegaly. The pathophysiological bedrock of HS consists of the retention and damage of abnormal red cells, caused by an intrinsic erythrocyte membrane defect. Hemolysis within the spleen is the main detrminant of erythrocyte destruction in patients with HS. Splenectomy removes the primary ?graveyard? for spherocytes and, thus, eliminates anemia and hyperbilirubinemia and lowers the high reticulocyte number to nearly normal levels. Spleen removal is an effective therapeutic option but it is not without risks. The incidence and public health impact of spleen surgery in children with HS is substantial. Unfortunately, splenectomy is sometimes recommended erroneously for young children who have a mild clinical phenotype or is performed without relying on careful assessment of the risks and benefits. This article aims to present criticism and address controversy about HS management. Unclear and still controversial issues are tackled according to the author?s personal viewpoint, because strong evidence in different aspects of HS management is lacking. PMID- 22077528 TI - A new era for IFN-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. AB - In recent years, several studies have shown that IFN-?2 is able to induce molecular remissions with undetectable JAK2V617F in a subset of patients with essential thrombocythemia (ET) and polycythemia vera (PV), even with normalization of the bone marrow and sustained molecular remissions after discontinuation of IFN-?2. Accordingly, interest in using IFN-?2 in the treatment of patients with PV and related neoplasms has been revived. This article highlights the current status of IFN-?2 in the treatment of patients with ET, PV, primary myelofibrosis and myelofibrosis following ET and PV. In the context of being able to induce ?minimal residual disease? in a subset of patients after long-term treatment with IFN-?2, the current risk-stratification systems used for treatment decisions are being challenged. It is argued that in 2011, the bulk of evidence for the efficacy and safety of pegylated interferons in treating patients with these neoplasms favors the upfront use of pegylated interferons, the goal being to influence the development of the disease at the molecular level and revert patients to a stage of ?minimal residual disease/operational cure? instead of progressive clonal evolution, genomic instability and leukemic or myelofibrotic transformation during long-term treatment with hydroxyurea. PMID- 22077529 TI - Treatment of warfarin-associated coagulopathy with vitamin K. AB - Warfarin is the most common form of oral anticoagulant therapy. Although it has indisputable benefit in the management of thromboembolic disease, warfarin associated coagulopathy (WAC) is a well-documented complication of its use. As warfarin exerts its effect by impairing formation of the vitamin K-dependent clotting factors, a cornerstone of WAC management is vitamin K replacement. Daily vitamin K supplementation is an emerging approach to regulate international normalized ratios in difficult-to-control patients. Mild WAC without bleeding can often be managed with warfarin withdrawal alone. For excessive international normalized ratio elevation in the absence of bleeding, low-dose oral vitamin K (1?2.5 mg) is sufficient and achieves the same degree of international normalized ratio correction by 24 h as intravenous therapy. The stable patient with WAC and minor bleeding can also be given oral vitamin K, with correction of the underlying defect. Major bleeding should first be managed with factor replacement for immediate correction of the coagulopathy, using either a prothrombin complex concentrate or fresh-frozen plasma. High-dose vitamin K (10 mg) should be given concurrently via intravenous infusion to confer lasting correction. Warfarin resistance and vitamin K-associated anaphylaxis are rare. Despite development of new oral anticoagulant therapy compounds, warfarin will probably retain a prominent role in thromboembolism management for several years to come. PMID- 22077530 TI - Optimizing management of myelodysplastic syndromes post-allogeneic transplantation. AB - Allogeneic hematopoietic stem cell transplantation is still the only potentially curative treatment for patients with myelodysplastic syndromes. Improvements in donor selection, supportive care and the introduction of reduced-intensity conditioning have led to a decrease in early transplant mortality. However, relapse rates have not changed significantly in recent years. Furthermore, treatment options for patients relapsing after hematopoietic stem cell transplantation are limited and often short-lived. Thus, optimizing the post transplant outcome by maintenance approaches or minimal residual disease-directed preemptive therapy is an important goal of current clinical research. Further strategies aiming at an improved prevention of graft-versus-host disease are currently under investigation. PMID- 22077532 TI - Use of data linkage to investigate the aetiology of acute lower respiratory infection hospitalisations in children. AB - AIM: To document the aetiology of acute lower respiratory infection (ALRI) hospitalisations in Western Australian children by linking population-based laboratory data with hospital morbidity data. METHODS: Data from all ALRI hospitalisations and laboratory records related to respiratory pathogens between 2000 and 2005 were extracted and linked through a population-based record linkage system. The proportion of specimens that were positive for each respiratory viral or bacterial pathogen was documented. RESULTS: Eight thousand nine hundred and eighty (45.2%) ALRI hospitalisations were linked to a laboratory record. Admissions to a private hospital and admissions from non-metropolitan areas were less likely to have a linked laboratory record. In 57.9% of linked hospitalisations, a respiratory virus and/or a bacterial pathogen was identified. Frequently identified viral pathogens included respiratory syncytial virus (RSV; n= 3226; 39.5% of those tested), influenza viruses (n= 664; 8.5%), parainfluenza virus type 3 (n= 348; 4.6%), picornaviruses (n= 292; 22.3%) and adenoviruses (n= 211; 2.7%). RSV was identified in 63.7% of bronchiolitis admissions in those aged under 6 months and 33.1% of pneumonia admissions in those aged under 12 months. Influenza viruses were identified in 81.6% of influenza-coded admissions. When a test was requested, Bordetella pertussis was identified in 21.2% of ALRI hospitalisations (n= 354), including 86.8% of whooping cough-coded admissions. CONCLUSIONS: This is the first report of population-based data linkage between statewide laboratory data and hospitalisation records and demonstrates proof of principle. RSV continues to be an important pathogen in ALRI. As pathogens were identified across all diagnoses, relying on hospital diagnosis coding alone may not accurately estimate the burden of different categories of ALRI. PMID- 22077533 TI - Review of longitudinal studies of MRI brain volumetry in patients with traumatic brain injury. AB - INTRODUCTION: Structural brain imaging in patients with traumatic brain injury (TBI) has progressed remarkably over the years with respect to technology and study design. METHODS: Published studies of patients with TBI which used magnetic resonance imaging (MRI), volumetric measures and a longitudinal design--that is, one in which data were collected at more than one point in time--were reviewed. Some of these studies also included analyses using a cross-sectional (one point in time) approach. RESULTS: Ten studies met the review criteria. Although methods varied, these studies showed a consistent pattern of brain atrophy which progressed over the months after injury. Effect sizes (brain size differences) between patients and normal control subjects generally were much larger for comparisons using the longitudinal approach than for those using a cross sectional approach. Furthermore, atrophy correlated significantly with important clinical variables. CONCLUSION: In comparison with the cross-sectional design, the longitudinal design may be preferable for understanding the progression of brain atrophy after injury and understanding its association with important clinical variables. PMID- 22077534 TI - The role of anxiety sensitivity in symptom perception after minor head injury: an exploratory study. AB - PRIMARY OBJECTIVE: This exploratory study examined the role of anxiety sensitivity (AS) as a factor contributing to outcome following minor head injury (MHI). Recent research has implicated AS in perception of pain intensity after orthopaedic trauma. AS, therefore, has the potential to mediate perception of and reaction to post-concussion symptoms at an early stage of recovery, increasing the risk of a protracted and incomplete recovery. RESEARCH DESIGN: A case series analysis. METHODS AND PROCEDURES: Sixty-three head trauma patients referred from an accident and emergency unit to an acute minor head injury service were compared to 58 patients who had suffered recent orthopaedic injury. Participants completed the Rivermead Post-Concussion Questionnaire (RPQ), to determine the number and severity of head injury-related symptoms, and the Anxiety Sensitivity Index (ASI), to measure their emotional reaction to symptoms. MAIN OUTCOMES AND RESULTS: Significant between-group differences were found for both RPQ and ASI measures. The MHI group reported more serious symptoms. Both groups also recorded significant positive correlations between the RPQ and ASI measures, with a stronger relationship recorded for the MHI group. CONCLUSIONS: The results support the impression that anxiety sensitivity may be an important factor mediating perception of symptoms after injury, potentially influencing speed and quality of recovery. PMID- 22077535 TI - Assessment of symptoms in a concussion management programme: method influences outcome. AB - CONTEXT: Monitoring of subjective symptoms is the foundation of all sport concussion management programmes. The purpose of this study is to examine methodological variables that impact symptom reporting during baseline testing. OBJECTIVE: To investigate how the administration method of a concussion assessment tool (self-report vs interview) affects the report of symptoms. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, semi-randomized study of 117 athletes. MAIN OUTCOME MEASUREMENTS: Subjects completed the Post Concussion Scale during pre-season evaluations. RESULTS: A two-factor ANOVA revealed a significant difference in total symptom scores (p = 0.02) and number of endorsed symptoms (p = 0.02) across administration modes. Athletes had a greater total symptom score and reported a greater number of symptoms in the self administration condition than in the interview condition. Furthermore, there was a significant difference in symptom reporting across interviewer gender. Athletes endorsed more symptoms when the interviewer was a woman. CONCLUSIONS: Because the method of collecting symptoms, as well as interviewer gender, can impact test results, self-report measures may be a better way of obtaining consistent results. Clinicians and researchers should be aware that both the nature and extent of symptom reporting is greater when using questionnaires than when athletes are interviewed. PMID- 22077536 TI - Independence in managing one's finances after traumatic brain injury. AB - PRIMARY OBJECTIVE: To establish whether the budgeting task of the Instrumental Activities of Daily Living (IADL) Profile discriminates individuals with a traumatic brain injury (TBI) from healthy controls and to identify the nature of the observed difficulties. METHOD: This study tested 27 adults with moderate or severe TBI and 27 controls matched for age, sex and education on the budgeting task of the IADL Profile. The budgeting task is a complex real-world problem involving the preparation of a yearly budget for an individual living on a fixed income with the goal of saving money to purchase a car. MAIN RESULTS: The results showed that TBI subjects, the majority of whom had documented frontal lesions and/or diffuse axonal injury based on CT scan reports, were more likely than control subjects to experience difficulties on all task-related operations (planning, carrying out and verifying attainment of goal), with planning being particularly affected. These deficits were shown to impact on financial abilities, an issue of particular concern for TBI individuals reporting full responsibility of their finances. CONCLUSIONS: The budgeting task of the IADL Profile discriminates TBI subjects from controls. Planning was shown to be the most significant difficulty underlying reduced independence in the task. PMID- 22077537 TI - To exclude or not to exclude: white matter hyperintensities in diffusion tensor imaging research. AB - OBJECTIVE: A practical methodological issue for diffusion tensor imaging (DTI) researchers is determining what to do about incidental findings, such as white matter hyperintensities (WMHI). The purpose of this study was to compare healthy control subjects with or without WMHIs on whole brain DTI. METHOD: Participants were 30 subjects (age = 37.7, SD = 11.3, Range = 18-60; 70% female) who had no known developmental, general medical, neurological or psychiatric condition that could have had an adverse affect on brain morphology. RESULTS: MRI (3 Tesla) revealed, at minimum, a WMHI in eight subjects (26.7%). Fractional anisotropy (FA) was calculated for 19 regions of interest (ROI). Frequency distributions of FA scores for the 19 ROIs were calculated. The 10th percentile for each ROI was selected as a cut-off score. Having four or more low FA scores occurred in 16.7%. More subjects with incidental findings met criterion for low FA scores (37.5%), compared to 9.1% of subjects with no findings. When subjects with minor WMHIs were retained and only those with multiple incidental findings were excluded, 8.3% of the retained subjects met criterion for low FA scores compared to 50.0% of the excluded subjects. CONCLUSIONS: The decision to include or exclude subjects who have incidental findings can influence the results of a study. PMID- 22077540 TI - Everyday life for the spouses of patients with untreated OSA syndrome. AB - The aim of this study was to generate a theoretical model describing concerns for spouses of patients with untreated obstructive sleep apnoea syndrome (OSAS) and how they manage these concerns in their everyday life. Twelve spouses were interviewed about their experiences and how they manage everyday life. The interviews were analysed according to the Grounded Theory method as described by Strauss and Corbin. Two main categories emerged from the data: 'Social adjustment' and 'New feelings'. 'Social adjustment' reveals how the spouses made adjustments in their daily lives, both according to their partners' tiredness and owing to their own fatigue. 'New feelings' reveals emotional reactions related to the effects of their partner's illness and the impact it had on the spouse's everyday life. These two main categories could be seen in relation to four dimensions describing how the spouses manage their everyday life: 'Sacrificing', 'Controlling', 'Changing' and 'Understanding'. The results show how the spouses made adjustments in everyday life and how their feelings were affected by their partner's OSAS. Healthcare personnel could use information from this study to gain a deeper understanding and knowledge of what spouses of untreated patients with OSAS experience as their main concerns and how they manage their everyday life. This knowledge can be used to improve the support to the spouses, as well as in the educational situation concerning the illness, as well as the treatment. PMID- 22077541 TI - Assessment of hospice health professionals' knowledge, views, and experience with medical marijuana. AB - The medicinal and recreational use of cannabis has been controversial, especially in the United States. Marijuana for medicinal use is approved in 14 U.S. states and has recently been considered for legalization in several additional states. Given its demonstrated efficacy in symptom management, marijuana has a potential role in palliative care. This study utilized a 16-item questionnaire to assess the knowledge, experience, and views of hospice professionals regarding the use of marijuana in terminally ill patients. The study results revealed that, like the general public, hospice health care providers are generally in favor of legalization of marijuana and, if legalized, would support its use in symptom management for their terminally ill patients. PMID- 22077542 TI - "My baby is a person": parents' experiences with life-threatening fetal diagnosis. AB - Diagnosis of a lethal fetal diagnosis (LFD) early in pregnancy is devastating for parents. Those who choose to continue with the pregnancy report intense emotional reactions and inconsistent, often insensitive treatment by health care providers. This qualitative descriptive study sought to clarify the experiences and needs of families in order to design responsive perinatal palliative care services, and to establish the feasibility and acceptability of conducting intensive interviews of pregnant women and their partners during their pregnancy with a LFD. We interviewed 2 women and 3 couples during pregnancy or just after birth, using open ended questions. Audiotaped responses were analyzed by two investigators. Two dimensions and six themes emerged. In the dimension of Personal Pregnancy Experience, "Grieving Multiple Losses" elucidates that parents grieve the loss of their normal pregnancy, healthy baby and future parenting. "Arrested Parenting" describes their sudden interruption in the normal process of becoming a parent. The theme "My Baby is a Person" reflects parents' unanimous desire to honor and legitimize the humanity of their unborn baby. In the dimension of Interactions of Others, three themes were found. "Fragmented Health Care" describes parent's disjointed and distant encounters with multiple providers. "Disconnected Family and Friends" describes the lack of understanding of what the families were experiencing. "Utterly Alone," which crosses both dimensions, expresses how the parents' sense of social isolation adds to their personal sense of loss and loneliness. Recommendations are made for palliative care's role in respecting and validating the experience of parents living through a doomed pregnancy. PMID- 22077543 TI - Freezing in sealed capillaries for preparation of frozen hydratedsections. PMID- 22077544 TI - Association of interleukin-10 gene promoter polymorphisms with chronic and aggressive periodontitis. AB - OBJECTIVE: Interleukin-10 gene promoter polymorphisms have been associated with interleukin-10 decreased production, thereby playing a role in the pathogenesis of periodontitis. This study aimed to investigate whether interleukin-10 single nucleotide polymorphisms at positions -1087(G/A) and -597(C/A) are associated with generalised chronic periodontitis and localised aggressive periodontitis. METHODS: Genomic DNA samples were isolated from 276 unrelated Jordanian participants. Subjects were categorised into 86 periodontally healthy controls, 105 chronic periodontitis patients and 85 localised aggressive periodontitis patients. Genotype frequencies were calculated, and differences were determined using Pearson chi-squared test, and odds ratio and 95% confidence intervals were included. RESULTS: The frequencies of the -1087A and -597A alleles were significantly more common in chronic periodontitis patients than controls. The A positive allele genotypes (GA, AA) at position -1087 and A-positive allele genotypes (CA, AA) at position -597 appeared to increase the risk of having chronic periodontitis. No significant differences were observed in the genotype frequencies between localised aggressive periodontitis patients and controls. CONCLUSIONS: These findings indicate the possible use of interleukin-10 single nucleotide polymorphisms as genetic markers in chronic periodontitis patients and further emphasise the molecular differences between chronic periodontitis and aggressive periodontitis. PMID- 22077545 TI - Urological litigation. PMID- 22077547 TI - Laparoscopic extravesical ureteric re-implantation. PMID- 22077546 TI - Management of low (favourable)-risk prostate cancer. AB - What's known on the subject? and What does the study add? Most men who are diagnosed with favourable-risk prostate cancer undergo some form of active intervention, despite evidence that treatment will not improve health outcomes for many. The decision to undergo treatment after diagnosis is, in part, related to the inability to precisely determine the long-term risk of harm without treatment. Nevertheless, physicians should consider patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments, before recommending a management option. This is especially important for older men, given the high level of evidence that those with low-risk disease are unlikely to accrue any benefit from curative intervention. What is known on the subject: Over treatment of favourable-risk prostate cancer is common, especially among older men. What does the study add: A review of the natural history of favourable-risk prostate cancer in the context of choices for management of the disease. * The management of favourable-risk prostate cancer is controversial, and in the absence of controlled trials to inform best practice, choices are driven by personal beliefs with resultant wide variation in practice patterns. * Men with favourable-risk prostate cancer diagnosed today often undergo treatments that will not improve overall health outcomes. * A shared decision approach for selecting optimal management of favourable-risk disease should account for patient age, overall health, and preferences for living with cancer and the potential side effects of curative treatments. PMID- 22077548 TI - Vaginal extraction after laparoscopic nephrectomy. PMID- 22077549 TI - Will 2012 be a good year? PMID- 22077551 TI - Nepal Trek raises funds for prostate cancer research: 'There are no easy walks in the Himalayas'. PMID- 22077552 TI - Caveolin-1 and cancer metabolism in the tumor microenvironment: markers, models, and mechanisms. AB - Caveolins are a family of membrane-bound scaffolding proteins that compartmentalize and negatively regulate signal transduction. Recent studies have implicated a loss of caveolin-1 (Cav-1) expression in the pathogenesis of human cancers. Loss of Cav-1 expression in cancer-associated fibroblasts results in an activated tumor microenvironment, thereby driving early tumor recurrence, metastasis, and poor clinical outcome in breast and prostate cancers. We describe various paracrine signaling mechanism(s) by which the loss of stromal Cav-1 promotes tumor progression, including fibrosis, extracellular matrix remodeling, and the metabolic/catabolic reprogramming of cancer-associated fibroblast, to fuel the growth of adjacent tumor cells. It appears that oxidative stress is the root cause of initiation of the loss of stromal Cav-1 via autophagy, which provides further impetus for the use of antioxidants in anticancer therapy. Finally, we discuss the functional role of Cav-1 in epithelial cancer cells. PMID- 22077554 TI - Optical absorption and emission properties of fluoranthene, benzo[k]fluoranthene, and their derivatives. A DFT study. AB - Fluoranthene and benzo[k]fluoranthene-based oligoarenes are good candidates for organic light-emitting diodes (OLEDs). In this work, the electronic structure and optical properties of fluoranthene, benzo[k]fluoranthene, and their derivatives have been studied using quantum chemical methods. The ground-state structures were optimized using the density functional theory (DFT) methods. The lowest singlet excited state was optimized using time-dependent density functional theory (TD-B3LYP) and configuration interaction singles (CIS) methods. On the basis of ground- and excited-state geometries, the absorption and emission spectra have been calculated using the TD-DFT method with a variety of exchange correlation functionals. All the calculations were carried out in chloroform medium. The results show that the absorption and emission spectra calculated using the B3LYP functional is in good agreement with the available experimental results. Unlikely, the meta hybrid functionals such as M06HF and M062X underestimate the absorption and emission spectra of all the studied molecules. The calculated absorption and emission wavelength are more or less basis set independent. It has been observed that the substitution of an aromatic ring significantly alters the absorption and emission spectra. PMID- 22077553 TI - Pathogenesis of plexiform neurofibroma: tumor-stromal/hematopoietic interactions in tumor progression. AB - Neurofibromatosis type 1 (NF1) is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene. A second hit mutation precedes the predominant NF1 neoplasms, which include myeloid leukemia, optic glioma, and plexiform neurofibroma. Despite this requisite NF1 loss of heterozygosity in the tumor cell of origin, nontumorigenic cells contribute to both generalized and specific disease manifestations. In mouse models of plexiform neurofibroma formation, Nf1 haploinsufficient mast cells promote inflammation, accelerating tumor formation and growth. These recruited mast cells, hematopoietic effector cells long known to permeate neurofibroma tissue, mediate key mitogenic signals that contribute to vascular ingrowth, collagen deposition, and tumor growth. Thus, the plexiform neurofibroma microenvironment involves a tumor/stromal interaction with the hematopoietic system that depends, at the molecular level, on a stem cell factor/c-kit-mediated signaling axis. These observations parallel findings in other NF1 disease manifestations and are clearly relevant to medical management of these neurofibromas. PMID- 22077555 TI - Actinic granuloma occurring in an unusual association with cutaneous B-cell chronic lymphocytic leukemia. AB - Granulomatous cutaneous reactions are well described in association with T-cell non-Hodgkin lymphoma and Hodgkin lymphoma, but are rarely seen in association with B-cell non-Hodgkin lymphoma or leukemia. We report a case of a 65-year-old woman with B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who presented with multiple, tender, firm pink papules on the face, upper trunk and upper extremities 6 years after diagnosis of CLL. Biopsy revealed both palisading granulomatous dermatitis consistent with actinic granuloma and a dense perivascular lymphocytic infiltrate consistent with the patient's known history of leukemia. This is an unusual manifestation of cutaneous B-cell CLL that is rarely seen. PMID- 22077557 TI - Reviews on animal diseases recently published in other journals. PMID- 22077556 TI - Safety of quadrivalent human papillomavirus vaccine. PMID- 22077560 TI - Constrained density functional theory. PMID- 22077559 TI - Screening of antimicrobial activity of Cistus ladanifer and Arbutus unedo extracts. AB - In this work, the in vitro antimicrobial activity of different crude extracts obtained from Cistus ladanifer L. and Arbutus unedo L. was investigated. The ethanol, methanol and acetone/water extracts of Cistus ladanifer and Arbutus unedo were prepared using different extraction methods and their antimicrobial activities against reference strains, including three Gram-positive, five Gram negative and three yeasts, and against clinical isolates of Helicobacter pylori and methicillin-resistant Staphylococcus aureus, were investigated. All the extracts inhibited more than one microorganism; moreover all of them presented antimicrobial activity against the Gram-positive bacteria, Klebsiella pneumonia, Candida tropicalis and Helicobacter pylori. It is noteworthy that the most considerable in vitro effect was observed against Helicobacter pylori. These inhibitory effects can be considered relevant to the development of new agents for inclusion in the treatment or prevention of infections by the tested strains. PMID- 22077561 TI - Differential expression of canonical and non-canonical Wnt ligands in ameloblastoma. AB - BACKGROUND: Canonical and non-canonical Wnt signaling pathways modulate diverse cellular processes during embryogenesis and post-natally. Their deregulations have been implicated in cancer development and progression. Wnt signaling is essential for odontogenesis. The ameloblastoma is an odontogenic epithelial neoplasm of enamel organ origin. Altered expressions of Wnts-1, -2, -5a, and -10a are detected in this tumor. The activity of other Wnt members remains unclarified. MATERIALS AND METHODS: Canonical (Wnts-1, -2, -3, -8a, -8b, -10a, and -10b), non-canonical (Wnts-4, -5a, -5b, -6, 7a, -7b, and -11), and indeterminate groups (Wnts-2b and -9b) were examined immunohistochemically in 72 cases of ameloblastoma (19 unicystic [UA], 35 solid/multicystic [SMA], eight desmoplastic [DA], and 10 recurrent [RA]). RESULTS: Canonical Wnt proteins (except Wnt-10b) were heterogeneously expressed in ameloblastoma. Their distribution patterns were distinctive with some overlap. Protein localization was mainly membranous and/or cytoplasmic. Overexpression of Wnt-1 in most subsets (UA = 19/19; SMA = 35/35; DA = 5/8; RA = 7/10) (P < 0.05), Wnt-3 in granular cell variant (n = 3/3), and Wnt-8b in DA (n = 8/8) was key observations. Wnts-8a and 10a demonstrated enhanced expression in tumoral buddings and acanthomatous areas. Non-canonical and indeterminate Wnts were absent except for limited Wnt-7b immunoreactivity in UA (n = 1/19) and SMA (n = 1/35). Stromal components expressed variable Wnt positivity. CONCLUSION: Differential expression of Wnt ligands in different ameloblastoma subtypes suggests that the canonical and non canonical Wnt pathways are selectively activated or repressed depending on the tumor cell differentiation status. Canonical Wnt pathway is most likely the main transduction pathway while Wnt-1 might be the key signaling molecule involved in ameloblastoma tumorigenesis. PMID- 22077562 TI - Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. AB - BACKGROUND: Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response. METHODS: In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG associated inhibitory activity were evaluated. RESULTS: A time- and dose dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = 0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12). CONCLUSIONS: Functional assays of inhibitory IgG(4) and IgE-blocking factor may be more useful surrogates of clinical response than IgG(4). Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation. PMID- 22077563 TI - Are babies consumer durables? A Critique of the Economic Theory of Reproductive Motivation * The research discussed is supported by a grant from The Equitable Life Assurance Society to International Population and Urban Research, Institute of International Studies, University of California, Berkeley. The author wishes to thank Kingsley Davis for his advice and criticism, and Valerie Caires, Katherine Carter and Barbara Heyns for their assistance in processing the studies involved in this analysis. The report is also indebted to General Research Support Grant of the National Institutes of Health (1501-TR-544104) for assistance to Statistical Services, School of Public Health. AB - Abstract Never before have couples been able to control so effectively the number of children they will have. Although involuntary factors still affect family size, continuing advances in contraceptive techniques make deliberate choice an ever more important determinant of fertility. But what factors determine the size of family people will choose ? One type of answer advanced in recent years by Gary Becker views reproductive performance simply as economic behaviour. Couples, he believes, desire fewer children when poor, more when rich. PMID- 22077564 TI - Natality and ethnocentrism: Some relationships suggested by an analysis of catholic-protestant differentials. AB - Abstract At the time of writing, the Roman Catholic Church is engaged in a major re-evaluation of its position on contraception. Judging from newspaper interest, there exists a widespread assumption that Catholic teaching, together with the political and social influence of the Catholic clergy, is an important deterrent to the practice of contraception and, for that reason, to the reduction of human natality. PMID- 22077565 TI - A comparison of the size of families of roman catholics and non-catholics in Great Britain. AB - Abstract In a recent study of family size ideals in the D.S.A. it was found that in the 1960'S the mean ideal family size of Catholics was about half a child higher than the mean ideal size of non-Catholics. This note describes an analysis of similar data for married women in Great Britain, derived from an investigation undertaken in 1966 for the Population Investigation Committee. A difference in ideal family size, which was of the same order as the American difference, was found; and, in addition, the actual fertility of Catholics was compared with that of others. PMID- 22077566 TI - The verification of data in historical demography. AB - Abstract In all scientific studies care must be taken to work on data which are correct and hence to make sure of the quality of the observations. In the field of historical demography there is need for extra care. The data were collected a long time ago in circumstances which were sometimes good, sometimes bad, but often little known. Statisticians are, moreover, on a priori grounds, rather inclined to be more suspicious of observations made in the past than of those which are made currently. Results relating to past populations must therefore be more rigorously established than any others if they are to be accepted. The verification of the data thus forms an integral part of the work of the historical demographer. PMID- 22077567 TI - Fertility and nuptiality changes in Spain from the late 18th to the early 20th century. AB - Abstract 1.1. The course of Spanish population growth from the end of the 16th to the beginning of the 18th century was set by the effects of what demographers call 'catastrophic' mortality. As in most European populations, the occasional but recurrent ravages of epidemics, especially plague, wiped out the excess of births over deaths accumulated in 'normal' years. How accurate and close to reality this statement is cannot be discussed here; but we shall assume that, until the rSth century, short-term growth was offset by mortality above the normal levels caused by epidemics. PMID- 22077568 TI - Fertility trends in Europe since the second world war. AB - Abstract Before discussing the movements in fertility in Europe since World War II, it is necessary to consider, both as a background and a yardstick for measurement, the general situation around the mid-1930's. This period has been chosen for several reasons. First, it was at about this time that the crude birth rates and other period indices of fertility in most Western and North-Western countries of Europe reached their lowest points. The decline initiated in the 1870's and 1880's had proceeded without interruption except for the years immediately after World War I, and had gathered momentum in the 1920's. Only in France, in which the birth rate had been falling throughout the 19th century, did there appear to be some approach to stabilization. Secondly, pro-natalist policies began to expand in France, Belgium and Italy, and were initiated in Germany with the Nazi takeover. The very expansion of such policies reinforced the feeling of impending depopulation in other Western countries, a feeling made more intense by the increasingly frequent use of period net reproduction rates as indicators of national 'vitality' ('true' rates of natural increase were much less frequently cited: they required more elaborate computations and appeared to be less striking). Such rates were regarded as sophisticated and meaningful measures of replacement tendencies and they were given a semi-official status by inclusion in the League of Nations Statistical Yearbooks. The apparent implications of these rates were made even more sharply visible by the publication of population projections constructed on a component basis, and using essentially the same approach as that embodied in net reproduction rates - that is, with fertility measured in terms of age-specific fertility rates, and with no regard paid to nuptiality. Thirdly, the early thirties saw the great economic depression, with its correlate of mass unemployment, and offering a natural economic explanation for at least part of the apparent demographic depression. PMID- 22077569 TI - Fertility differentials in the Sudan (with reference to the nomadic and settled populations) * This paper is based on a chapter from a Ph.D. thesis completed at the London School of Economics, under the joint supervision of Professor D. V. Glass and Dr. J. G. C. Blacker, to whom I am deeply indebted for guidance, criticism and suggestions. I am also grateful to the Ford Foundation and the Population Council Inc. for the grants which made this work possible. AB - Abstract Statistically valid records of birth and death registration do not yet exist in the Sudan. The 1955/56 sample census gave some evidence - though not very conclusive 1 The evidence from the 1955/56 sample census is not quite conclusive, partly because the administrative divisions for which the census data are available do not always coincide with the ethnic or mode of life divisions. Further, the available indices are inadequate and unreliable, and throw no light on the possible causes of the differentials. For further details see my article on 'Population of the Sudan' in Essays on Sudan Economy, forthcoming. - that there were fertility differentials in the country. These differentials were of three main types. First, there were differentials between the inhabitants of the three Southern provinces where recorded fertility levels were exceptionally - indeed suspiciously - high; and the Northern provinces where recorded fertility levels were considerably lower. Second, within the Northern populations, there appeared to be fertility differentials between the settled agricultural populations on the one hand, and the pastoral nomads on the other, fertility among the latter being apparently unusually low. Third, there was some evidence of urban-rural differentials. PMID- 22077570 TI - Some comments on Ursula M. Cowgill's article, 'life and death in the sixteenth century in the city of York' (Population Studies, July 1967). AB - Abstract The initial purpose of Miss Cowgill's investigation was to study possible differences in mortality according to the season of birth, a study in which groups of people must be followed from birth to death. In the present case the groups were composed of people born in six parishes of the City of York between 1538 and 1601. PMID- 22077571 TI - A reply to M. Henry's comments on Cowgill's article (Population Studies, July 1967). AB - Abstract To settle the excellent question that M. Henry has raised will undoubtedly require more research. At present the 17th-eentury York situation is being investigated. The number of matched births and deaths will be considerably greater than that obtained from a study ofthe 16th-century records. PMID- 22077576 TI - QALYs and carers. AB - When going 'beyond the patient', to measure QALYs for unpaid carers, a number of additional methodological considerations and value judgements must be made. While there is no theoretical reason to restrict the measurement of QALYs to patients, decisions have to be made about which carers to consider, what instruments to use and how to aggregate and present QALYs for carers and patients. Current, albeit limited, practice in measuring QALY gains to carers in economic evaluation varies, suggesting that there may be inconsistency in judgements about whether interventions are deemed cost effective. While conventional health-related quality-of-life tools can, in theory, be used to estimate QALYs, there are both theoretical and empirical concerns over the suitability of their use with carers. Measures that take a broader view of health or well-being may be more appropriate. Incorporating QALYs of carers in economic evaluations may have important distributional consequences and, therefore, greater normative discussion over the appropriateness of incorporating these impacts is required. In the longer term, more flexible forms of cost-per-QALY analysis may be required to take account of the broader impacts on carers and the weight these impacts should receive in decision making. PMID- 22077577 TI - Modelling the cost effectiveness of treatments for Parkinson's disease: a methodological review. AB - The objective of this review was to assess models of cost effectiveness for Parkinson's disease (PD) published after July 2002 and to derive recommendations for future modelling. A systematic literature search was performed in the databases PubMed, Current Contents, EMBASE, EconLit, the Cochrane Database of Systematic Reviews, and DARE (Database of Abstracts of Reviews of Effectiveness), NHS EED (Economic Evaluation Database) and HTA (Health Technology Assessment) of the UK NHS Centre for Review and Dissemination (July 2002 to March 2010). Only fully published studies using decision trees, Markov models, individual simulation models or sets of mathematical equations were included. Most of the 11 studies identified used Markov models (n = 9) and two employed were based on decision trees. Based on the Hoehn & Yahr (HY) scale, authors evaluated the cost effectiveness of drug treatments (n = 6), surgical approaches such as deep brain stimulation (n = 1) or striatal cell grafting (n = 1), and diagnostic procedures such as single photon emission computed tomography (SPECT) testing (n = 3) over a time horizon of 1 year to lifetime. Costs were adapted to address a societal and/or healthcare provider/third-party payer perspective. All but one of the interventions investigated were considered cost effective or cost saving. Cost effectiveness modelling in PD between 2003 and 2010 showed only minor improvement when compared with our earlier review of models published from 1998 up to 2003. Cost-effectiveness modelling recommendations were complied with to only a limited extent, leaving room for quality improvement. More advanced modelling approaches may, so far, be under-represented, but may be used in the future, driven by the research question. Adverse events of treatment, co-morbidities or disease complications are not yet sufficiently included in the models to adequately represent clinical reality. PMID- 22077578 TI - Cost-effectiveness analysis of prophylactic lamivudine use in preventing vertical transmission of hepatitis B virus infection. AB - BACKGROUND: As neonates born to mothers with positive hepatitis B e antigen may not be completely protected by hepatitis B vaccination, prophylactic lamivudine use in mothers with high viraemia has been proposed. However, the overall effectiveness and the balance between cost and benefit for such a prophylactic strategy have rarely been addressed. OBJECTIVE: Using a review of recent literature, we aimed to assess the cost effectiveness, from the Taiwanese societal perspective, of administering prophylactic lamivudine to mothers to reduce vertical transmission of hepatitis B virus and its long-term sequelae in neonates. METHODS: A meta-analysis of three randomized controlled trials was conducted to evaluate the efficacy of lamivudine versus placebo. A Markov decision model was constructed in which in both treatment arms infants received active and passive immunoprophylaxis. An economic evaluation was performed to calculate costs, acute infections averted, and QALYs gained. Probabilistic sensitivity analyses were conducted and a cost-effectiveness acceptability curve drawn. All these analyses were from the societal perspective. Costs ($US) were valued in year 2008 prices. RESULT: Supplemental lamivudine use gained an additional 0.0024 QALYs and averted 0.23 acute infections per birth compared with the routine active-passive immunization without lamivudine. The cost effectiveness analysis suggested that the use of additional prophylactic lamivudine dominated the routine strategy. The acceptability curve suggested that the probability of being cost effective under the willingness-to-pay threshold of $US20,000 was 94%. CONCLUSION: This analysis suggests that supplemental use of lamivudine in mothers with high hepatitis B viraemia is effective in reducing vertical transmission and may be cost effective, from a Taiwanese societal perspective, compared with the routine active-passive immunization without lamivudine. PMID- 22077579 TI - Cost effectiveness of tenofovir disoproxil fumarate for the treatment of chronic hepatitis B from a Canadian public payer perspective. AB - INTRODUCTION: Previous research has demonstrated that tenofovir disoproxil fumarate (DF) is the most cost-effective nucleos(t)ide treatment for chronic hepatitis B (CHB) in the UK, Spain, Italy and France. However, to our knowledge, no published studies have yet evaluated the cost effectiveness of any treatments for CHB in a Canadian setting, where relative prices and management of CHB differ from those in Europe. AIM: Our objective was to determine the cost effectiveness of tenofovir DF compared with other nucleos(t)ide therapies licensed for CHB in Canada from the perspective of publicly funded healthcare payers. METHODS: A Markov model was used to calculate the costs and benefits of nucleos(t)ide therapy in three groups of patients with hepatitis B e antigen (HBeAg)-positive and -negative CHB: nucleos(t)ide-naive patients without cirrhosis; nucleos(t)ide naive patients with compensated cirrhosis; and lamivudine-resistant patients. Disease progression was modelled as annual transitions between 18 disease states. Transition probabilities, quality of life and costs were based on published studies. Health benefits were measured in QALYs. The reference year for costs was 2007 and costs and outcomes were discounted at 5% per annum. RESULTS: First-line tenofovir DF was the most effective nucleos(t)ide strategy for managing CHB, generating 6.85-9.39 QALYs per patient. First-line tenofovir DF was also the most cost-effective strategy in all patient subgroups investigated, costing between $Can43,758 and $Can48,015 per QALY gained compared with lamivudine then tenofovir. First-line tenofovir DF strongly dominated first-line entecavir. Giving tenofovir DF monotherapy immediately after lamivudine resistance developed was less costly and more effective than any other active treatment strategy investigated for lamivudine-resistant CHB, including second-line use of adefovir or adefovir + lamivudine. Probabilistic sensitivity analysis demonstrated 50% confidence that first-line tenofovir DF is the most cost-effective nucleos(t)ide strategy for treatment-naive patients with CHB, at a $Can50,000 per QALY threshold, and confirmed that first-line tenofovir DF has the highest expected net benefits. CONCLUSIONS: First-line tenofovir DF appears to be the most cost effective nucleos(t)ide treatment for both cirrhotic and non-cirrhotic CHB patients in Canada, providing that society is willing to pay at least $Can48,015 per QALY gained, although sensitivity analyses highlighted uncertainty around the results. PMID- 22077580 TI - Girls' schooling and the perceived threat of adolescent sexual activity in rural Malawi. AB - Despite its relative infrequency, pregnancy is perceived by parents in rural Malawi as a leading cause of school dropout among female students. This paper explores parents' beliefs about adolescent sexual activity and schoolgirl pregnancy and how these perceptions frame parents' aspirations and expectations about girls' schooling. In-depth interviews were collected in rural Malawi from 60 adults aged 25-50 who were the parent of at least one school-aged child. Four themes emerged from the data: how expectations about sexual activity frame parental expectations about schooling duration and dropout, the loss of parental control, the negative influence of classmates and schools as unsafe environments. These concerns frame how parents consider a daughter's schooling prospects and are active even for parents whose daughters are not sexually active or who are not yet old enough to have gone through puberty. Although all parents aspire for their children to attend secondary school, these perceptions of daughters' relative risk weaken parents' motivation to encourage daughters to remain in school. PMID- 22077581 TI - Novel clinical and molecular findings in Chinese families with dyschromatosis symmetrica hereditaria. PMID- 22077583 TI - In silico homology modeling to predict functional properties of cruciferin. AB - Cruciferin is the major storage protein in Brassicaceae family oilseeds. The predominant cruciferin isoforms in Arabidopsis thaliana were investigated using homology modeling (HM) for their molecular structures and functional properties. The structure of Brassica napus procruciferin was used as the template for HM to determine the molecular structures and hypervariable regions. Hydrophobicity and electrostatic surface potential distribution on the intradisulfide-containing face (IA) and the interdisulfide-containing face (IE) indicated favorable interfacial and solubility properties. More heat-induced structural changes were predicted for the CruC homotrimer than for the CruA or CruB homotrimers. Structural features that facilitate flavor binding and limit proteolytic digestion were more readily observed in CruA and CruB than in CruC. On the basis of these comparative models, structural differences among cruciferin isoforms and their relevance to potential technofunctionalities were identified. This approach of functional property prediction will link protein structure to utilities and will be valuable in designing proteins for targeted applications. PMID- 22077584 TI - Acute disc herniation in the elderly. AB - BACKGROUND: Acute disc prolapse in young adults has been studied extensively. However, little is known about acute disc prolapse in the elderly. OBJECTIVE: We aimed to define the features of acute disc prolapse in the elderly. DESIGN, SETTING AND PATIENTS: Elderly (>= 65 years) patients who had lumbar or thoracic discectomy for acute (< 3 months) disc prolapse in our unit between July 2004 and March 2010 were identified. For comparison, we used a 'young' (25-45 years) patient cohort with acute thoracic or lumbar disc prolapse. Data collected included age, symptom onset, preoperative signs and spinal level. RESULTS: During the study period, 390 patients had discectomy, of which 59.7% were 'young' and 7.4% 'elderly'. The young and elderly patients had significantly different distributions of prolapsed disc levels. In the young, 97% of all disc protrusions were at L4/5 or L5/S1, but < 50% were at these levels in the elderly. In the elderly, about 10% of disc protrusions were thoracic. CONCLUSIONS: Acute disc prolapse is rare in the elderly and primarily affects the upper lumbar and lower thoracic spine. PMID- 22077582 TI - Noninvasive detection of passively targeted poly(ethylene glycol) nanocarriers in tumors. AB - The present studies noninvasively investigate the passive tumor distribution potential of a series of poly(ethylene glycol) (PEG) nanocarriers using a SkinSkan spectrofluorometer and an In Vivo Imaging System (IVIS) 100. Fluorescein conjugated PEG nanocarriers of varying molecular weights (10, 20, 30, 40, and 60 kDa) were prepared and characterized. The nanocarriers were administered intravenously to female balb/c mice bearing subcutaneous 4T1 tumors. Passive distribution was measured in vivo (lambda(exc), 480 nm; lambda(em), 515-520 nm) from the tumor and a contralateral skin site (i.e., control site). The signal intensity from the tumor was always significantly higher than that from the contralateral site. Trends in results between the two methods were consistent with tumor distribution increasing in a molecular weight-dependent manner (10 < 20 < 30 ? 40 ? 60 kDa). The 10 kDa nanocarrier was not detected in tumors at 24 h, whereas 40-60 kDa nanocarriers were detected in tumors for up to 96 h. The 30, 40, and 60 kDa nanocarriers showed 2.1, 5.3, and 4.1 times higher passive distribution in tumors at 24 h, respectively, as compared to the 20 kDa nanocarrier. The 60 kDa nanocarrier exhibited 1.5 times higher tumor distribution than 40 kDa nanocarrier at 96 h. Thus, PEG nanocarriers (40 and 60 kDa) with molecular weights close to or above the renal exclusion limit, which for globular proteins is >=45 kDa, showed significantly higher tumor distribution than those below it. The hydrodynamic radii of PEG polymers, measured using dynamic light scattering (DLS), showed that nanocarriers obtained from polymers with hydrodynamic radii >=8 nm exhibited higher tumor distribution. Ex vivo mass balance studies revealed that nanocarrier tissue distribution followed the rank order tumor > lung > spleen > liver > kidney > muscle > heart, thus validating the in vivo studies. The results of the current studies suggest that noninvasive dermal imaging of tumors provides a reliable and rapid method for the initial screening of nanocarrier tumor distribution pharmacokinetics. PMID- 22077585 TI - Solitary fibrous tumour of the vagus nerve. AB - We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve root. This ninth case of immunohistologically confirmed cranial or spinal nerve SFT is the first of the vagus nerve. PMID- 22077587 TI - A case of craniocervical abscess with sinus thrombosis in Lemierre's syndrome. AB - A 74-year old gentleman with a cranio-cervical abscess failed to improve after incision and drainage and standard intravenous antibiotic therapy. Imaging demonstrated thrombosis of the internal jugular vein, sigmoid sinus and transverse sinus; and microbiological analysis isolated Fusobacterium nucleatum. The diagnosis of Lemierre's syndrome was confirmed, and he was effectively treated with appropriate antibiotics and anti-coagulation. PMID- 22077586 TI - Management of head trauma due to landmine explosions: from battle field to operation room. AB - BACKGROUND: Head injuries due to landmine explosions are not well studied and the management of such injuries is not documented, even though there is, unfortunately, a regrettably high incidence of such injuries in the military and in civilians. METHODS: The data of 119 patients who underwent surgery for the head injuries due to landmine explosions were reviewed retrospectively. All of these patients were military personnel, and the mean age was 23 years. RESULTS: A total 83 (69.7%) of the cases were injured by the anti-personnel devices and 36 (30.3%) by vehicle landmines. Fifty percent of the patients underwent surgery for depressed skull fracture, intraparenchymal foreign body, epidural haematoma or subdural haematoma. Six (0.05%) patients died in the emergency room. CONCLUSION: Landmine explosions can produce classic injury patterns from blunt and penetrating mechanisms to several organ systems, including the brain. They also produce unique injury patterns to the brain. Understanding this important difference is critical in management of these injuries. Early surgical treatment and appropriate management could save more lives. PMID- 22077588 TI - Intraoperative sealing of dura mater defects with a novel, synthetic, self adhesive patch: application experience in 25 patients. AB - BACKGROUND: The quest for an ideal sealant for dura mater defects persists. The clinical experience with a novel, synthetic self-adhesive patch (TissuePatchDural((r)), Tissuemed, Leeds, UK) and its ability to prevent postoperative cerebrospinal fluid (CSF) leakage is described in this article. METHODS: A recently developed, synthetic, self adhesive patch was implanted in 25 patients who underwent intradural neurosurgical procedures. The indication for use was to adjunctively seal dura mater defects. The device is a multi-laminate consisting of thin films of a commonly used structural polymer, poly(lactide-co glycolide) and a tissue reactive polymer providing fast and strong chemical bonding of the patch with the underlying biological surface. Intraoperative handling and efficacy, biocompatibility, and postoperative observations/follow-up were analysed. Infectious complications, surgical wound features, and postoperative MRI scans were especially reviewed. The mean follow up period was 4.4 months. RESULTS: The device provided fast and efficacious sealing of circumscribed dura mater defects within 1 minute in 23 patients (92%). Two of 25 patients developed a postoperative CSF leakage (8%), which may be secondary to particular factors predisposing these patients to CSF leaks. Surgical handling was straightforward. No infectious complications were recorded; furthermore, wound healing was unremarkable. No clinical evidence of foreign body reactions was observed. In 18 patients, postoperative MRI scans were available which did not show irregularities in any case. CONCLUSIONS: Safe and effective sealing can be accomplished with this bioabsorbable, purely synthetic and thin dural sealant, avoiding the application of foreign biologic material. The product has been shown to be effective in achieving watertight closure of the dura mater and has prevented CSF leakage in 92% of patients treated. PMID- 22077589 TI - Pattern of head injuries in Malta (EU): a small Mediterranean island. AB - We have reviewed all acute neurosurgical admissions between December 2007 and December 2009. Hundred and nine (46.6%) of our admissions were head injuries. A subdural haematoma(SDH) was found in 51.4%(56) of the head injuries. Of these, 50/56 presented with a Glasgow Coma Scale(GCS) of 14 to 15, 41.1% (23) of these SDH needed surgery. The commonest mode of injury was falls [67.9%(74) of head injuries]. Risk factors for falls are co-morbidities which are particular to an elderly population, these include osteoarthritis and audio/ visual impairment. Falls are more common in rural areas where elderly are more likely to feel comfortable to walk and sustain trivial falls resulting in chronic subdural heamatomas. PMID- 22077591 TI - Prenuptial dental extractions in Acadian women: first report of a cultural tradition. AB - BACKGROUND: Prenuptial tooth extractions, extractions of all teeth in at least one dental arch before marriage, are not identified in the dental literature. Driven by a professional encounter, the purpose of this study was to confirm the existence of this practice among Acadian women. METHODS: An 8-item survey instrument with space for comments was mailed to 182 dentists from traditionally Acadian regions of Canada. The survey was provided in English and French. RESULTS: Ninety dentists responded (50.3%); 8 of them (9%) had been asked to perform prenuptial extractions, and an additional 9 volunteered awareness of this practice. Awareness and requests were associated with dental practice in a county with a >=20% French-speaking population. CONCLUSIONS: Prenuptial extractions in this population have been confirmed by the current cohort of dentists. The potential public health, clinical, and systemic health research implications for women who are edentulous for most of their adult life merit further study. Additionally, it is important to determine if interventions are needed to curtail cultural expectations of such practices. PMID- 22077590 TI - The discoidin domain receptor 1 gene has a functional A2RE sequence. AB - Discoidin domain receptor 1 (DDR1) is expressed in myelin oligodendrocytes and co localizes with myelin basic protein (MBP). Alternative splicing of DDR1 generates five isoforms designated DDR1a-e. The MBP mRNA contains an hnRNP A2 response element (A2RE) sequence that is recognized by heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, which is responsible for transport of the MBP mRNA to oligodendrocyte processes. We hypothesized that DDR1 could have a functional A2RE sequence. By in silico analysis, we identified an A2RE-like sequence in the human DDR1 mRNA. We observed nuclear and dendrite cytoplasmic immunofluorescence, indicating that DDR1 and hnRNP A2/B1 co-localize in human oligodendrocytes and in differentiated HOG16 cells. The A2RE-like sequence of DDR1 contains the single nucleotide polymorphism rs2267641, and we found that in the human brain, the minor allele is associated with lower and higher levels DDR1b and DDR1c mRNA expression, respectively. Moreover, a positive correlation between DDR1c and the myelin genes myelin-associated glycoprotein and oligodendrocyte lineage transcription factor 2 was found. Differentiated HOG16 cells transfected with an hnRNP A2/B1 siRNA simultaneously show a decrease and an increase in the DDR1c and DDR1b mRNA expression levels, respectively, which was accompanied by a decrease in DDR1 protein levels at the cytoplasmic edges. These results suggest that the DDR1 A2RE sequence is functionally involved in the hnRNP A2/B1-mediated splicing and transport of the DDR1c mRNA. PMID- 22077592 TI - An essay about health professionals' attitudes to lesbian, gay, bisexual and transgender parents seeking healthcare for their children. AB - BACKGROUND: This paper is a polemic essay about an important but sometimes controversial subject. Lesbian, gay, bisexual and transgender (LGBT) clients can be reluctant to reveal their sexual orientation to health professionals from whom they may be seeking health care for their children. Family-centred care (FCC), where care is planned around the whole family not just the individual child, is widely used across the world, but unless all aspects of the families who present for care are respected, care delivery is compromised. This is particularly important for minority groups and potentially vulnerable families such as LGBT. AIM: This descriptive essay discusses the use of health services by LGBT parents, how seeking health care is influenced by perceived perceptions of LGBT people held by health professionals, and examines factors affecting such seeking of health care. DISCUSSION: We show that LGBT people may be unwilling to disclose sexual identity to health professionals when seeking health care for their children. Health professional's attitudes can be affected by factors such as gender, age, religious and political affiliations, education level and previous interactions with LGBT people. CONCLUSION: We conclude our argument with the assertion that all parents, including those from minority groups such as LGBT, who bring their children for health care need supportive family-centred care, and only by ensuring that the health professionals delivering care are well educated about all aspects of sexuality will care be family-centred. PMID- 22077593 TI - Transatlantic Consensus Group on active surveillance and focal therapy for prostate cancer. AB - What's known on the subject? and What does the study add? Active surveillance for prostate cancer is gaining increasing acceptance for low risk prostate cancer. Focal therapy is an emerging tissue preservation strategy that aims for treat only areas of cancer. Early phase trials have shown that side-effects can be significantly reduced using focal therapy. There is significant uncertainty in both active surveillance and focal therapy. This consensus group paper provides a road-map for clinical practice and research for both tissue-preserving strategies in the areas of patient population, tools for risk stratification and cancer localisation, treatment interventions as well as comparators and outcome measures in future comparative trials. OBJECTIVE: To reach consensus on key issues for clinical practice and future research in active surveillance and focal therapy in managing localized prostate cancer. PATIENTS AND METHODS: A group of expert urologists, oncologists, radiologists, pathologists and computer scientists from North America and Europe met to discuss issues in patient population, interventions, comparators and outcome measures to use in both tissue-preserving strategies of active surveillance and focal therapy. Break-out sessions were formed to provide agreement or highlight areas of disagreement on individual topics which were then collated by a writing group into statements that formed the basis of this report and agreed upon by the whole Transatlantic Consensus Group. RESULTS: The Transatlantic group propose that emerging diagnostic tools such as precision imaging and transperineal prostate mapping biopsy can improve prostate cancer care. These tools should be integrated into prostate cancer management and research so that better risk stratification and more effective treatment allocation can be applied. The group envisaged a process of care in which active surveillance, focal therapy, and radical treatments lie on a continuum of complementary therapies for men with a range of disease grades and burdens, rather than being applied in the mutually exclusive and competitive way they are now. CONCLUSION: The changing landscape of prostate cancer epidemiology requires the medical community to re-evaluate the entire prostate cancer diagnostic and treatment pathway in order to minimize harms resulting from over diagnosis and over-treatment. Precise risk stratification at every point in this pathway is required alongside paradigm shifts in our thinking about what constitutes cancer in the prostate. PMID- 22077594 TI - Association of 3BP2 with SHP-1 regulates SHP-1-mediated production of TNF-alpha in RBL-2H3 cells. AB - Adaptor protein 3BP2, a c-Abl Src homology 3 (SH3) domain-binding protein, is tyrosine phosphorylated and positively regulates mast cell signal transduction after the aggregation of the high affinity IgE receptor (FcepsilonRI). Overexpression of the Src homology 2 (SH2) domain of 3BP2 results in the dramatic suppression of antigen-induced degranulation in rat basophilic leukemia RBL-2H3 cells. Previously, a linker for activation of T cells (LAT) was identified as one of the 3BP2 SH2 domain-binding protein. In this report, to further understand the functions of 3BP2 in FcepsilonRI-mediated activation of mast cell, we explored the protein that associates with the SH2 domain of 3BP2 and found that SH2 domain containing phosphatase-1 (SHP-1) inducibly interacts with the SH2 domain of 3BP2 after the aggregation of FcepsilonRI. The phosphorylation of Tyr(564) in the carboxy (C)-terminal tail region of SHP-1 is required for the direct interaction of SHP-1 to the SH2 domain of 3BP2. The expression of the mutant form of SHP-1 which was unable to interact with 3BP2 resulted in the significant reduction in SHP-1-mediated tumor necrosis factor-alpha (TNF-alpha) production without any effects on the degranulation in antigen-stimulated RBL-2H3 cells. These findings suggest that 3BP2 directly interacts with Tyr(564) -phosphorylated form of SHP-1 and positively regulates the function of SHP-1 in FcepsilonRI-mediated signaling in mast cells. PMID- 22077595 TI - Spectroscopic structure-property relationships of a series of polyaromatic platinum acetylides. AB - To develop a structure-spectroscopic property relationship in platinum acetylides having poly(aromatic hydrocarbon) ligands, we synthesized a series of chromophores with systematic variation in the number of fused aromatic rings (nFAR) and ligand topology (polyacene (L), polyphenanthrene (Z), or compact(C)). We measured ground-state absorption, fluorescence, and phosphorescence spectra. We also performed nanosecond and femtosecond transient absorption experiments. To extend the range of compounds in the structure-property relationship, we did DFT calculations on an expanded series of chromophores. Both the DFT results and experiments show that the S(1) and T(1) state energies are a function of both nFAR and the ligand topology. In the L chromophores, the S(1) and T(1) state energies decrease linearly with nFAR. In contrast, the S(1) and T(1) state energies of the Z chromophores oscillate around a fixed value with increasing nFAR. The C chromophores have behavior intermediate between the L and Z chromophores. A parallel series of calculations on the ligands shows the same behavior. The S(1)-S(n) energy obtained from ultrafast time-resolved spectra has a linear variation in nFAR. The rate constant for nonradiative decay, k(nr), was calculated from the S(1) state lifetime and decreases with an increasing number of pi electrons in the aromatic ring. The result is consistent with the spin orbit coupling caused by the central platinum heavy atom decreasing with larger nFAR. The present work shows that the framework developed for the analysis of poly(aromatic hydrocarbon) properties is useful for the understanding of the corresponding platinum acetylide complexes. PMID- 22077596 TI - Kumada coupling of aryl, heteroaryl, and vinyl chlorides catalyzed by amido pincer nickel complexes. AB - A series of amido pincer complexes of nickel were examined for their catalysis in the Kumada cross-coupling reaction. The P,N,O-pincer nickel complexes tested are active catalysts for the cross-coupling of aryl, heteroaryl, and vinyl chlorides with aryl Grignard reagents. The reactions can proceed at room temperature and tolerate functional groups in aryl chlorides with the aid of LiCl and ZnCl(2) additives. PMID- 22077597 TI - Proteomic characterization of the greening process in rice seedlings using the MS spectral intensity-based label free method. AB - Illumination-induced greening in dark-grown plants is one of the most dramatic developmental processes known in plants. In our current study, we characterized the greening process of rice seedlings using comparative proteome analysis. We identified 886 different proteins in both whole cell lysates of illuminated and nonilluminated rice shoots and performed comparative proteome analysis based on the MS spectral intensities obtained for unique peptides from respective proteins. Furthermore, the changes in the levels of individual proteins were then compared with those of the corresponding mRNAs. The results revealed well coordinated increases in the enzymes involved in the Calvin cycle at both the protein and mRNA levels during greening, and that the changes at the mRNA level precede those at the protein level. Although a much lower effect of illumination was found on the enzymes associated with glycolysis and the TCA cycle, coordinated increases during greening were evident for the enzymes involved in photorespiration and nitrogen assimilation as well as the components of the chloroplastic translational machinery. These results thus define the differential regulation of distinct biological systems during greening in rice and demonstrate the usefulness of comprehensive and comparative proteome analysis for the characterization of biological processes in plant cells. PMID- 22077598 TI - Reviews on animal diseases recently published in other journals. PMID- 22077600 TI - Hemifacial preferences for the perception of emotion and attractiveness differ with the gender of the one beheld. AB - Though the left cheek appears more emotive, perceptions of attractiveness vary with gender. For the first time, this study assessed the relationship between perceptions of emotion (happiness) and attractiveness in naturalistic photographic portraits. One hundred ninety-two participants (63 male; 129 female) viewed pairs of left and right cheek poses, and made a forced-choice decision indicating which image appeared (a) more emotive and (b) more attractive (order counterbalanced). Half the images were mirror-reversed to control for perceptual biases. Results indicated a striking gender difference: for males, the left cheek appears both more emotive and more attractive; for females, preferences are subject to stronger perceptual influences, with the right cheek bias for emotion and attractiveness reversing to a left cheek bias when images are mirror reversed. These findings suggest that if you want to show the world your "best side", men should lead with the left but for women, the right cheek is right. PMID- 22077602 TI - Update 1 of: C2-symmetric chiral bis(oxazoline) ligands in asymmetric catalysis. PMID- 22077601 TI - Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases. AB - Primary cutaneous amyloidosis includes several forms of localized amyloidosis characterized by superficial amyloid deposits occurring at or near the dermal epidermal junction in the absence of systemic involvement. Primary cutaneous amyloidosis of the auricular concha and external ear represents a rarely described variant. There have been 27 cases reported in the English language literature, and herein we report 17 additional cases. This article demonstrates that the amyloid observed in this context is generally positive for Congo red, crystal violet and thioflavin T. It also expresses cytokeratin 34betaE12 via immunohistochemistry. Our immunohistochemical results and review of the literature suggest that the amyloid in amyloidosis of the external ear is the result of basal keratinocyte degeneration and does not signify deposition from a systemic or generalized process. PMID- 22077603 TI - Experiences of unmarried young abortion-seekers in Bihar and Jharkhand, India. AB - While several studies have documented the prevalence of unprotected pre-marital sex among young people in India, little work has explored one of its likely consequences, unintended pregnancy and abortion. This paper examines the experiences of 26 unmarried young abortion-seekers (aged 15-24) interviewed in depth as part of a larger study of unmarried abortion-seekers at clinics run by an NGO in Bihar and Jharkhand. Findings reveal that recognition of the unintended pregnancy was delayed for many and many who suspected so further delayed acknowledging it. Once recognised, most confided in the partner and, for the most part, partners were supportive; a significant minority, including those who had experienced forced sex, did not have partner support and delayed the abortion until the second trimester of pregnancy. Family support was absent in most cases; where provided, it was largely to protect the family reputation. Finally, unsuccessful attempts to terminate the pregnancy were made by several young women, often with the help of partners or family member. Findings call for programmes for young women and men, their potential partners, parents and families and the health system that will collectively enable unmarried young women to obtain safe abortions in a supportive environment. PMID- 22077604 TI - Pitfalls in benefit-cost analysis of birth prevention. AB - Abstract The paper summarizes the procedure usually employed by Enke, Meier and others to estimate the benefit-cost ratio of a prevented birth. Some possible deficiencies in the formulation, the possible lack of relevance of the resulting computations, are considered. For example, since the benefit-cost ratios are exceptionally high they would imply unusually high rates of investment for family planning. The results would also apply for the birth prevention of not only high parity births, but also for first and second children. Some arguments are presented which suggest the possibility that the income distribution might be worsened as a consequence of the application of a family planning programme based on these principles - especially those which employ subsidies to induce the practice of family limitation. In addition it is also argued that the average economic quality of the population may be lower than otherwise as a consequence of such programmes, and that the consequences of such events are not taken into account in the usual formulation. Also the usual estimates of costs of such programmes are questioned since the relation between acceptances and births prevented are unknown given the lack of knowledge about the substitution between the proposed methods of family limitation and other means of population control. Finally, we present a model based on reasonable but different assumptions than the formulation popularized by Enke and others, and show that on the basis of this model it is possible to obtain results which are the exact opposite of the Enke model. Also it is argued that the model presented is much more sensitive to actual data than the usual formulation. PMID- 22077605 TI - The patterns and causes of fertility differentials in the Sudan (with reference to nomadic and settled populations). AB - Abstract A demographic survey was undertaken in the Sudan for the purpose of studying fertility differentials between the nomadic and settled populations. In a previous publication the magnitude of these differentials was examined. The present paper examines the nature of the differentials and possible causes are then assessed. These causes are divided into two categories: those arising from the differential marriage patterns and those which are broadly termed 'medical and physiological'. Under the former heading it was found that larger proportions of nomadic women were still single, while those who had married had tended to do so at later ages, more had experienced broken marriages, and more were in polygamous marriages. Under the latter heading it was found that the nomadic women had experienced higher rates of pregnancy loss, appeared to show a high incidence of venereal disease and malaria, and tended to breast-feed their children for periods two to three times as long as the women in agricultural communities. Nutritional standards among the nomads were also substantially lower, and may well have affected fecundity. PMID- 22077606 TI - Size and structure of the household in England over three centuries. AB - Abstract Data giving sizes and structures of households have been rare for any country before the institution of the official census, and have to be gleaned from surviving documents containing listings of inhabitants. This article, the first of two, describes the collection of listings of inhabitants of English communities which is being assembled by the Cambridge Group for the History of Population and Social Structure and the methods by which the hundred most informative of them have been submitted to analysis. When ranged alongside the information on mean household size derived from the official British census since its inception in 1801, the results of this analysis suggest the following. 1. Mean household size in England and Wales as a whole was relatively constant at 4.75 or a little below for the whole period from the sixteenth century until 19II, and has only fallen since that date. The reduction of about one-third starting in 1921 may therefore be the first of considerable magnitude ever to occur: it seems to have been particularly rapid between 1911 and 1931. 2. Mean household size in England and Wales has been surprisingly resistant to demographic fluctuation on the one hand and to the structural influences of industrialization on the other, until the last fifty or sixty years. 3. The traditional household in England has never been extended on any definition, at least since the sixteenth century. Mean household size varied with social status, and a majority lived in households of six or more members. But this distribution was due to the very large numbers of servants living in and not to the presence of resident kin, who seem to have been rare. 4. The relationship between fertility, mortality and mean household size is different from what has been supposed. This article ends by registering the paradox that proportion of children in a pre-industrial English community apparently seems to be negatively, not positively, related to its mean household size, and this theme will be taken up in the second article. These four points are illustrated by a series of tables drawn from the analysis of the one hundred communities. PMID- 22077607 TI - Expectancy of life at birth in 36 nationalities of the Soviet Union: 1958-60. AB - Abstract In the 36 nationalities of the Soviet Union the estimated expectancy of life at birth ranged from 50.0 years for Chechens to 71.1 years for Latvians with a median of about 67.5 years for Russians. In essence, the life table function e(0) was generated from the child-woman ratios with the use of intricate equations based on empirical data obtained from official Soviet publications. A modified version of Bourgeois-Pichat's model was used to estimate life expectancies at birth among the 36 nationalities on the basis of their crude death rates and the percentage of population aged 65 years and over. The 1959 U.S.S.R. Census of Population provided information pertaining to the older age groups. The crude death rates were estimated separately with the aid of second degree polynomials fitted to the crude demographic measures for 109 administrative areas of the Soviet Union for 1960. Information about recent improvements in public health, as well as conjectural evaluations of economic advancement in recent years were examined and related to the past and present level of mortality among the Russian people and the remaining population of minorities. PMID- 22077608 TI - Inferences about abortion from foetal mortality data. AB - Abstract In a longitudinal fertility study in Detroit the evidence indicates that the foetal mortality rate in the prospective periods are better reported than in retrospective parts of the fertility histories. While the data do not specifically differentiate between induced abortions and other foetal deaths, the foetal death rates vary in relation to other social and demographic characteristics of the couples in such a way as make induced abortion a consistently plausible explanation of differentials. Foetal mortality rates tend to be high among sub-groups which have the incentive, information and the financial means for induced abortions. If these inferences are correct, it is likely that there is a considerable practice of induced abortion. PMID- 22077609 TI - Contraceptive acceptance and pregnancy: a matrix approach to the analysis of competing risks. AB - Abstract This paper represents an initial attempt to formalize the relationships among post-partum sterility, fecundability, and contraceptive acceptance in terms of absorbing Markov chains. Acceptance of contraception offered by family planning programmes is analyzed as a possible event in time for a cohort of recently delivered women as they pass through phases of temporary sterility and fecundability towards another possible pregnancy. The results of the study indicate that once a woman leaves the post-partum anovulatory stage, the probability of her becoming pregnant again is large compared to the competing rates of contraceptive acceptance currently in force. Unless highly fecund non contracepting women are approached by family planning programmes shortly after a pregnancy has been terminated (by childbirth or abortion), they will quickly become ineligible to accept either the pill or IUD because of once again being 'currently pregnant'. PMID- 22077610 TI - Desired family size and the efficacy of current family planning programmes. AB - Abstract This paper takes a look at the belief that the number of couples currently desiring to limit family size is sufficiently large (and the intensity of their desire sufficiently strong) that the provision of supplies, services and education - the standard family planning package - will be adequate to bring the birth rate down to acceptable levels within a reasonable time period. Evidence comes from other countries, from attitude surveys and behavioural studies in India, from a priori considerations about what is reasonable to expect, and from certain demographic considerations. The most reasonable conclusion to draw from this evidence is that the belief is not correct. If the birth rate is to be brought down to target levels, additional methods - perhaps monetary incentives - seem to be necessary. PMID- 22077611 TI - Malaria eradication and its effect on mortality levels: A comment. AB - Abstract In his article 'Malaria eradication and its effect on mortality levels' (Population Studies d21, 3, November 1967) Dr. S. A. Meegama criticised the approach followed by Professor Peter Newman in an earlier investigation of the effects of malaria eradication in Ceylon. In the present series of comments and rejoinders, Professor Newman and Dr. Meegama discuss in detail their interpretations of the data and the methods they have used in assessing the role of malaria eradication. PMID- 22077612 TI - The decline in maternal and infant mortality and its relation to malaria eradication. AB - Abstract In his article 'Malaria eradication and its effect on mortality levels' (Population Studies d21, 3, November 1967) Dr. S. A. Meegama criticised the approach followed by Professor Peter Newman in an earlier investigation of the effects of malaria eradication in Ceylon. In the present series of comments and rejoinders, Professor Newman and Dr. Meegama discuss in detail their interpretations of the data and the methods they have used in assessing the role of malaria eradication. PMID- 22077613 TI - Rejoinder. PMID- 22077614 TI - A reply. PMID- 22077617 TI - An optimized growth factor cocktail for ovine mesenchymal stem cells. AB - Growth factors that regulate proliferation, migration, and invasion of ovine mesenchymal stem cells (oMSCs) are not well defined. In this study, we have evaluated five growth factors for their ability to initiate and support in vitro proliferation, migration, and invasion of oMSCs. oMSCs were exposed to different doses and combinations of the growth factors: basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), insulin growth factor-I (IGF-I), connective tissue growth factor, and platelet-derived growth factor-AB (PDGF-AB). Cellular proliferation, motility, and invasiveness were assayed. The most proliferative stimulating growth factors are PDGF-AB+TGF-beta and PDGF-AB+IGF-I. Combinations EGF+bFGF and EGF+bFGF+PDGF AB demonstrated the greatest ability to stimulate migration. Moreover, the triple cocktail EGF+bFGF+TGF-beta has the most significant effect on invasion. Different growth factor cocktails are required to enhance proliferation, migration, and invasion. These results may be useful for the development of a tissue-engineered heart valve by stimulating cellular repopulation. PMID- 22077618 TI - Effects of sarpogrelate hydrochloride on skin ulcers and quality of life in patients with systemic sclerosis. AB - 5-Hydroxytryptamine 2A serotonin receptor (5-HT(2A) ) is associated with the contraction of vascular smooth muscle, platelet aggregation and thrombus formation and coronary artery spasms. Sarpogrelate hydrochloride (sarpogrelate) is a selective 5-HT(2A) antagonist and was supposed to be effective for Raynaud's phenomenon with collagen disease. Sarpogrelate has not been investigated regarding the effects, safety and quality of life (QOL) in patient with skin ulcers of collagen disease. Eleven patients with skin ulcers and systemic sclerosis (SSc) were administrated sarpogrelate p.o. three times a day for 3-6 months. The area (mean +/- standard error) of skin ulcer at the pretreatment, and after 3 and 6 months of sarpogrelate intake was 2.1 +/- 0.8, 0.2 +/- 0.1 and 0.1 +/- 0.1 mm(2), respectively. The reduction of skin ulcer area was significant after 3 months of sarpogrelate intake. In assessment of QOL, scores of symptoms and emotions but not of functioning were significantly improved after sarpogrelate intake. The global score (mean +/- SE) of Skindex-16 at pretreatment, and after 3 and 6 months of sarpogrelate intake was 31.8 +/- 8.7, 23.7 +/- 8.3 and 10.9 +/- 4.6, respectively. The score was significantly improved after 6 months of sarpogrelate intake. There were no obvious side-effects during this study. Sarpogrelate was considered to be a useful drug to improve skin ulcers and QOL in patients with SSc. PMID- 22077619 TI - Patient preferences for first-line oral treatment for mild-to-moderate ulcerative colitis: a discrete-choice experiment. AB - BACKGROUND: Patients with ulcerative colitis (UC) frequently require long-term therapy to prevent relapse. Treatments such as 5-aminosalicylic acid (5-ASA [mesalazine]) are efficacious and well tolerated, but adherence to treatment is often poor. OBJECTIVE: This discrete-choice experiment (DCE) was conducted to estimate differences in patient preferences for 5-ASA treatment in mild-to moderate UC based on levels of self-reported adherence. Inclusion of patients residing in the US, UK, Germany, and Canada allowed for assessment of possible cultural differences in patient preferences. METHODS: DCE attributes were determined through literature review, clinician consultation, and patient interviews. Six treatment attributes were identified: ease of swallowing, time of day, quantity, extent of flare resolution, likelihood of flare occurrence, and cost. A total of 400 patients in four countries completed the DCE and adherence (Modified Morisky Scale) surveys. Data were analyzed using generalized estimating equations to estimate patient preference and willingness to pay (WTP) by levels of self-reported adherence and country of residence. RESULTS: All attributes had expected polarity and were significant predictors of patient preference. Self reported 'good' versus 'poor' adherers significantly preferred symptom control (p = 0.0108) and mucosal healing (p = 0.0190) attributes. All patients stated preference for symptom control/mucosal healing and flare risk attributes; the latter attribute was significantly preferred across all countries. Country differences in patient preference for convenience versus clinical attributes were found. Overall, patients were willing to pay L29.24 ($US46.27) per month for symptom control and mucosal healing, and an additional L78.81 ($US124.70) per month for reduction in flare risk to 10% per year (WTP costs were equalized between each country using the published 2008 purchasing power parity). Those with flares in the past year significantly preferred avoiding future flares (p < 0.0001) versus other attributes, as well as lower risk of flares (10%, likelihood ratio: 0.64-0.70). CONCLUSIONS: Findings indicate that self-reported adherers to UC therapy have a stronger preference for clinical benefits over other treatment attributes, suggesting that positive patient assessment of effectiveness may influence adherence. Ongoing clinician assessment of patient preferences for treatment attributes, as well as education on the importance of adherence, may help improve treatment outcomes in UC. PMID- 22077620 TI - Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies. AB - BACKGROUND: Evidence of an association between job strain and obesity is inconsistent, mostly limited to small-scale studies, and does not distinguish between categories of underweight or obesity subclasses. OBJECTIVES: To examine the association between job strain and body mass index (BMI) in a large adult population. METHODS: We performed a pooled cross-sectional analysis based on individual-level data from 13 European studies resulting in a total of 161 746 participants (49% men, mean age, 43.7 years). Longitudinal analysis with a median follow-up of 4 years was possible for four cohort studies (n = 42 222). RESULTS: A total of 86 429 participants were of normal weight (BMI 18.5-24.9 kg m(-2) ), 2149 were underweight (BMI < 18.5 kg m(-2) ), 56 572 overweight (BMI 25.0-29.9 kg m(-2) ) and 13 523 class I (BMI 30-34.9 kg m(-2) ) and 3073 classes II/III (BMI >= 35 kg m(-2) ) obese. In addition, 27 010 (17%) participants reported job strain. In cross-sectional analyses, we found increased odds of job strain amongst underweight [odds ratio 1.12, 95% confidence interval (CI) 1.00-1.25], obese class I (odds ratio 1.07, 95% CI 1.02-1.12) and obese classes II/III participants (odds ratio 1.14, 95% CI 1.01-1.28) as compared with participants of normal weight. In longitudinal analysis, both weight gain and weight loss were related to the onset of job strain during follow-up. CONCLUSIONS: In an analysis of European data, we found both weight gain and weight loss to be associated with the onset of job strain, consistent with a 'U'-shaped cross-sectional association between job strain and BMI. These associations were relatively modest; therefore, it is unlikely that intervention to reduce job strain would be effective in combating obesity at a population level. PMID- 22077622 TI - Human neutrophil alloantigen genotype frequencies among blood donors with Turkish and German descent. AB - Antibodies against the human neutrophil antigens (HNA) are able to stimulate transfusion reactions, autoimmune and neonatal neutropenia. The aim of this study was to determine the HNA allele frequencies in the largest ethnic minority group in Germany in comparison with the German population for predicting the risk of alloimmunization and associated transfusion reactions, as well as the risk of developing neonatal neutropenia for the newborn of racial mixed couples. However, there exists no data about HNA genotype distribution in Turkish population. DNA was isolated from blood samples of 119 German and 118 Turkish blood donors and typed them for HNA-1, -3, -4, and -5 by using a commercial polymerase chain reaction kit with sequence-specific primers (SSP-PCR) and compared the HNA genotype distribution of both groups. In German blood donors, the gene frequencies for HNA-1a and HNA-1b were 0.391 and 0.601, for HNA-3a and -3b, 0.744 and 0.256, for HNA-4a and -4b, 0.908 and 0.092, and for HNA-5a and -5bw, 0.731 and 0.269. In Turkish blood donors, we observed 0.420/0.564, 0.737/0.263, 0.881/0.119, and 0.754/0.246 for HNA-1a/1b, -3a/3b, -4a/4b, and -5a/5bw. No statistic significant difference between genotypes in these populations was observed. This study is the first to report HNA gene frequencies in a Turkish population. It showed that there is no difference of HNA genotype in blood donors with Turkish descent in comparison with German blood donors. The alternating transfusion of blood and blood components is no increased risk for developing alloantibodies against HNA antigens. In pregnancy of mixed couples no special screening programs for HNA are necessary. PMID- 22077621 TI - Natural killer cell engineering for cellular therapy of cancer. AB - Natural killer (NK) cells can kill transformed cells and represent a promising tool for the treatment of cancer. Their function is governed by a balance of stimulatory and inhibitory signals triggered by surface receptors. Advances in NK cell therapy require the development of dependable methods for obtaining an adequate number of effector cells; additional activation or genetic modification may further increase their anticancer capacity. A method for NK cell expansion used in our laboratory relies on a genetically modified form of the K562 myeloid leukemia cell line, engineered to express a membrane-bound form of interleukin-15 and the ligand for the costimulatory molecule 4-1BB (CD137). Expanded NK cells can be transduced with genes encoding chimeric antigen receptors that stimulate tumor cell-specific cytotoxicity. These methods for NK cell expansion and genetic modification have been adapted to large-scale, clinical-grade, Current Good Manufacturing Practice conditions and support two active clinical trials. Summarized are current efforts for NK cell immunotherapy for cancer and future perspectives. PMID- 22077623 TI - Genome-wide analysis of extended pedigrees confirms IL2-IL21 linkage and shows additional regions of interest potentially influencing coeliac disease risk. AB - Coeliac disease is a chronic inflammatory condition of the small intestine, triggered by dietary exposure to gluten in genetically susceptible individuals. Risk alleles at HLA-DQA1 and HLA-DQB1 are necessary for disease development, but are alone not sufficient for disease onset. We aimed to identify novel loci underlying susceptibility to coeliac disease through the use of extended Finnish and Hungarian families with multiple affected individuals. An initial whole genome linkage approach yielded several loci that were followed up further using the Immunochip custom array. Loci with a parametric logarithm of odds (LOD) score of >1.3 were identified at 4q, 6p [human leukocyte antigen (HLA) region], 6q, 7p, 17p, 17q and at 22p. The 4q and 6q loci have been identified previously in coeliac disease risk, whereas follow-up analyses indicate that the 17p and 22p loci may be novel risk loci for coeliac disease. These loci harbour previously described risk variants for other autoimmune diseases, but their segregation patterns do not explain the linkage to coeliac disease. We followed up the linkage to the 4q region, containing the previously described interleukin (IL)2 and IL21 genes. The risk variants at 4q in the studied pedigrees are most likely distinct from previously described risk variants, indicating that the observed linkage may be due to rare high-risk variants of still unknown nature. The importance of this locus to coeliac disease risk was further shown by the finding that serum levels of IL21 were elevated in both untreated and treated coeliac patients compared to controls. PMID- 22077624 TI - A CD40 single-nucleotide polymorphism affects the lymphocyte profiles in the bronchoalveolar lavage of Japanese patients with sarcoidosis. AB - CD40 plays a critical role in adaptive immunity, and alveolar macrophages in patients with sarcoidosis express higher levels of CD40. This study investigated the association of rs1883832, a functional single-nucleotide polymorphism in the CD40 gene with susceptibility to sarcoidosis and phenotypes of sarcoidosis. Genotyping of rs1883832 in 175 Japanese patients with sarcoidosis and 150 age- and sex-matched controls revealed no significant difference between the genotypes of the patient and control groups (CC/CT/TT, 32.8/52.0/14.7% in the patients; 37.3/48.0/14.7% in the controls, P = 0.66; allele C, 59.1% in the patients, 61.3% in the controls, P = 0.57). T-cell and CD4+ cell counts in the bronchoalveolar lavage fluid were significantly higher in the TT genotype group than in the CC and CT genotype group. PMID- 22077625 TI - Evaluation of DLA promoters in Doberman hepatitis. AB - Doberman hepatitis (DH) is associated with homozygous DLA DRB1*00601/DQA1*00401/DQB1*01303 indicating a role for the immune system in the development of the disease. The dog leucocyte antigen (DLA) class II expression is controlled at the transcriptional level with proximal promoters. Differential expression of DLA class II molecules of antigen-presenting cells is reported to affect susceptibility to or protection from different immune-mediated diseases. The aim of this study was to evaluate, whether the variation in promoter areas of homozygous DLA-DRB1*00601/DQA1*00401/DQB1*01303 Dobermans could explain why some dogs become afflicted with DH and others do not. Our findings suggest that promoter variants are not associated as risk modifiers in homozygous DLA DRB1*00601/DQA1*00401/DQB1*01303 Dobermans, but additional factors are needed. Nevertheless, our study indicates that the whole DLA block is associated to the disease. PMID- 22077626 TI - Nomenclature for factors of the HLA system, update July 2011. PMID- 22077627 TI - Nomenclature for factors of the HLA system, update August 2011. PMID- 22077628 TI - Nomenclature for factors of the HLA system, update September 2011. PMID- 22077629 TI - Bony presentations of childhood haematological malignancy to the emergency room. AB - AIM: Bony complaints are well-recognised symptoms of childhood haematological malignancy. However, this elusive symptom complex of haematological malignancy is not easily recognised in the emergency room (ER) where musculoskeletal problems are frequent. This study reviews bony complaints of childhood haematological malignancy in the ER. METHODS: This was a retrospective study of 148 children diagnosed with haematological malignancy between March 2002 and February 2007. RESULTS: Twenty-one cases (14.2%) presented with bony complaints to the ER within 3 months prior diagnosis of malignancy. The median age was 5.1 years, and majority (90.5%) had acute lymphoblastic leukaemia. Fifteen cases were undiagnosed for malignancy at first visit; diagnoses included pulled elbow, lower limb sprain and septic arthritis, with 21 days median time to correct diagnosis. In this undiagnosed group, history of trauma, fever, multiple bony site involvement, normal radiography and blood counts were common. Undiagnosed cases were referred to orthopaedics, paediatrics, rheumatology or the general practitioner, hospitalised or discharged without follow-up. CONCLUSION: The diagnosis of childhood haematological malignancy with first bony presentation to the ER was challenging, with a high prevalence of 71.4% undiagnosed cases at first visit. We highlight the common misdiagnoses because failure to correctly diagnose could delay timely institution of treatment. Trauma or normal investigations do not exclude an underlying haematological malignancy. This rare diagnosis in the ER should always be considered when challenged with recurrent bony complaints. PMID- 22077630 TI - Reappraisal of KIT mutation in adenoid cystic carcinomas of the salivary gland. AB - BACKGROUND: While overexpression of KIT protein has been well documented in adenoid cystic carcinomas (ACCs), mutation of KIT gene has been a controversial issue. We wanted to evaluate clinical value of the KIT mutation and protein expression in ACC. METHODS: We analyzed 33 cases of ACC. Gene mutations in KIT exons 9, 11, 13, and 17 were analyzed using paraffin-embedded tissue, and two different sets of primers with direct sequencing after polymerase chain reaction (PCR) for exon 9, 11, 13, and 17, and cloning of PCR products for exon 11. KIT protein expression was assessed by immunohistochemistry. The correlation between clinicopathological findings and these biomarkers was analyzed. RESULTS: No KIT mutation was observed in all of the 33 cases. With one primer set, KIT mutation was found in nine of 33 cases (27.3%). However, these mutations were not reproducible in the experiment using another primer set. KIT protein overexpression was detected in 22 of 33 patients (66.7%). KIT protein expression was not statistically correlated with either clinicopathological factors or survival. Patients with metastasis showed a tendency of longer progression-free survival (P = 0.052) and overall survival (P = 0.080) when the tumor overexpressed KIT protein. CONCLUSION: This study supports that mutational study using paraffin-embedded tissue should be interpreted with great caution. KIT gene mutation is very rare in ACC, and gene mutation is not the cause of protein overexpression. KIT protein expression may have a potential value for better prognostic factor in patients with metastasis. PMID- 22077631 TI - Herbivore-induced volatiles from tea (Camellia sinensis) plants and their involvement in intraplant communication and changes in endogenous nonvolatile metabolites. AB - As a defense response to attacks by herbivores such as the smaller tea tortrix ( Adoxophyes honmai Yasuda), tea ( Camellia sinensis ) leaves emit numerous volatiles such as (Z)-3-hexen-1-ol, linalool, alpha-farnesene, benzyl nitrile, indole, nerolidol, and ocimenes in higher concentration. Attack of Kanzawa spider mites ( Tetranychus kanzawai Kishida), another major pest insect of tea crops, induced the emission of alpha-farnesene and ocimenes from tea leaves. The exogenous application of jasmonic acid to tea leaves induced a volatile blend that was similar, although not identical, to that induced by the smaller tea tortrix. Most of these herbivore-induced plant volatiles (HIPV) were not stored in the tea leaves but emitted after the herbivore attack. Both the adaxial and abaxial epidermal layers of tea leaves emitted blends of similar composition. Furthermore, HIPV such as alpha-farnesene were emitted mostly from damaged but not from undamaged leaf regions. A principal component analysis of metabolites (m/z 70-1000) in undamaged tea leaves exposed or not to HIPV suggests that external signaling via HIPV may lead to more drastic changes in the metabolite spectrum of tea leaves than internal signaling via vascular connections, although total catechin contents were slightly but not significantly increased in the external signaling via HIPV. PMID- 22077632 TI - Unraveling the intracellular efficacy of dextran-histidine polycation as an efficient nonviral gene delivery system. AB - In this study, we attempted to elucidate the capability of a natural polymer dextran, by modification with histidine, to be an efficient, safe and promising nucleic acid delivery system in gene therapy. Physicochemical characterizations were performed to get an insight into the derivative. The efficiency of the derivative as a gene delivery vehicle was also studied in depth using fluorescence microscopy. Extensive efforts were made to have a better understanding of the cellular dynamics involved. The derivative proved itself to be 6.7-fold more excelling than PEI in its transfecting capability. Mechanisms underlying cellular internalization, vector unpacking, intranuclear localization and transgene expression were also investigated. The possibility of recruiting intracellular histone to promote the entry of the gene into the nucleus seemed promising. Our findings also explored the links that mediate the correlation between the uptake of the derivative and various endocytic pathways. The results thus obtained reflect the success of the entire journey of the synthesized delivery vehicle. PMID- 22077633 TI - Prognostic value of insulin-like growth factor II mRNA binding protein 3 in patients treated with radical prostatectomy. AB - Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Insulin-like growth factor II mRNA binding protein 3 (IMP3) is associated with poor outcomes in a variety of malignancies. The role of IMP3 in protate cancer remains poorly understood. IMP3 expression was associated with features of aggressive biology and aggressive prostate cancer recurrence after surgery. Although IMP3 is differentially expressed in patients with features of biologically aggressive prostate cancer, it does not have independent prognostic value in patients treated with RP. OBJECTIVE: To evaluate the association of insulin-like growth factor II mRNA binding protein 3 (IMP3) with pathological features and outcomes in patients treated with radical prostatectomy (RP). PATIENTS AND METHODS: Immunohistochemical staining for IMP3 was performed on archival tissue microarray specimens from 232 consecutive patients treated with RP for clinically localized disease. None of the patients received neoadjuvant or adjuvant radiation or hormone therapy. IMP3 expression was histologically categorized as normal or abnormal. Disease recurrence was classified as aggressive if metastases were present, post-recurrence prostate specific antigen (PSA) doubling time was less than 10 months, or if the patients failed to respond to salvage local radiation therapy. RESULTS: The median follow up was 69.8 months (interquartile range [IQR]: 40.1-99.5). IMP3 expression was abnormal in 42 (18.1%) of 232 patients. IMP3 expression was associated with extracapsular extension (P= 0.020), seminal vesicle invasion (P= 0.024), lymphovascular invasion (P= 0.036) and a high pathological Gleason score (P= 0.009). The 5-year PSA recurrence-free survival for IMP3-negative patients was 83% (standard error [SE]= 3) vs 67% (SE = 8) in IMP3-positive patients (log-rank test, P= 0.015). In a multivariable analysis that adjusted for the effects of surgical margins, extracapsular extension and seminal vesicle invasion, PSA (hazard ratio [HR]: 1.04, P= 0.013), lymph node metastasis (HR: 16.7, P < 0.001) and a high pathological Gleason score (HR 4.3, P= 0.008) were significantly associated with PSA recurrence-free survival, whereas IMP3 expression was not (P= 0.11). Similarly, IMP3 expression was only associated with aggressive recurrence (HR 3.2, P= 0.006). CONCLUSION: IMP3 expression is abnormal in approximately one fifth of prostate cancers. Although IMP3 is differentially expressed in patients with features of biologically aggressive prostate cancer, it does not have an independent prognostic value in patients treated with RP. PMID- 22077635 TI - An appropriate SCORE to assess cardiovascular risk in hypertension? PMID- 22077634 TI - Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease. AB - Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) brain. Our prior studies demonstrated reduced mitochondrial number in susceptible hippocampal neurons in the brain from AD patients and in M17 cells over expressing familial AD-causing amyloid precursor protein (APP) mutant (APPswe). In the current study, we investigated whether alterations in mitochondrial biogenesis contribute to mitochondrial abnormalities in AD. Mitochondrial biogenesis is regulated by the peroxisome proliferator activator receptor gamma coactivator 1alpha (PGC-1alpha)-nuclear respiratory factor (NRF)-mitochondrial transcription factor A pathway. Expression levels of PGC-1alpha, NRF 1, NRF 2, and mitochondrial transcription factor A were significantly decreased in both AD hippocampal tissues and APPswe M17 cells, suggesting a reduced mitochondrial biogenesis. Indeed, APPswe M17 cells demonstrated decreased mitochondrial DNA/nuclear DNA ratio, correlated with reduced ATP content, and decreased cytochrome C oxidase activity. Importantly, over-expression of PGC-1alpha could completely rescue while knockdown of PGC-1alpha could exacerbate impaired mitochondrial biogenesis and mitochondrial deficits in APPswe M17 cells, suggesting reduced mitochondrial biogenesis is likely involved in APPswe-induced mitochondrial deficits. We further demonstrated that reduced expression of p-CREB and PGC-1alpha in APPswe M17 cells could be rescued by cAMP in a dose-dependent manner, which could be inhibited by PKA inhibitor H89, suggesting that the PKA/CREB pathway plays a critical role in the regulation of PGC-1alpha expression in APPswe M17 cells. Overall, this study demonstrated that impaired mitochondrial biogenesis likely contributes to mitochondrial dysfunction in AD. PMID- 22077636 TI - Hepatitis in dogs. An indexed bibliography of journal articles (1994-2004). PMID- 22077638 TI - Membrane-bound transporter controls the circadian transcription of clock genes in Drosophila. AB - Little is known about molecular mechanisms that control the Drosophila circadian clock beyond the transcriptional-translational feedback regulation of clock genes as an intracellular process. In this study, Early gene at 23 (E23) was identified as a novel clock gene that encodes the membrane-bound ABC transporter that is induced by the molting hormone ecdysone. E23 expresses in pacemaker neurons in fly head, and its knockdown flies lengthened circadian period with an increased expression of the clock gene vrille. E23 and vrille responded to both ecdysone and clock signals, whereas E23 protein specifically suppressed the ecdysone response and is necessary for rhythmicity. Thus, E23 forms its own feedback loop in the ecdysone response to control circadian oscillation through ecdysone mediated vrille expression. The ecdysone signaling pathway with E23 is essential not only in developmental stage but also for the circadian behavior in adult fly. PMID- 22077639 TI - Relative quantitation of proteins in expressed prostatic secretion with a stable isotope labeled secretome standard. AB - Expressed prostatic secretion (EPS) is a proximal fluid directly derived from the prostate and, in the case of prostate cancer (PCa), is hypothesized to contain a repertoire of cancer-relevant proteins. Quantitative analysis of the EPS proteome may enable identification of proteins with utility for PCa diagnosis and prognosis. The present investigation demonstrates selective quantitation of proteins in EPS samples from PCa patients using a stable isotope labeled proteome standard (SILAP) generated through the selective harvest of the "secretome" from the PC3 prostate cancer cell line grown in stable isotope labeled cell culture medium. This stable isotope labeled secretome was digested with trypsin and equivalently added to each EPS digest, after which the resultant mixtures were analyzed by liquid chromatography-tandem mass spectrometry for peptide identification and quantification. Relative quantification of endogenous EPS peptides was accomplished by comparison of reconstructed mass chromatograms to those of the chemically identical SILAP peptides. A total of 86 proteins were quantified from 263 peptides in all of the EPS samples, 38 of which were found to be relevant to PCa. This work demonstrates the feasibility of using a SILAP secretome standard to simultaneously quantify many PCa-relevant proteins in EPS samples. PMID- 22077640 TI - Brooke-Spiegler syndrome: report of two cases not associated with a mutation in the CYLD and PTCH tumor-suppressor genes. AB - Brooke-Spiegler syndrome represents an autosomal dominant disease characterized by the occurrence of multiple cylindromas, trichoepitheliomas and (sporadically) spiroadenomas. Patients with Brooke-Spiegler syndrome are also at risk of developing tumors of the major and minor salivary glands. Patients with Brooke Spiegler syndrome have various mutations in the CYLD gene, a tumor-suppressor gene located on chromosome 16q. To date, 68 unique CYLD mutations have been identified. We describe two families with Brooke-Spiegler syndrome, one with familial cylindromatosis and one with multiple familial trichoepithelioma, which showed wide inter-family phenotypic variability. Analysis of germline mutations of the CYLD and PTCH genes was performed using peripheral blood. In addition, formalin-fixed paraffin-embedded tumor samples were analyzed for PTCH somatic mutations and cylindroma cell cultures were obtained directly from patients for further growth and analysis. Clinically, the major features of Brooke-Spiegler syndrome include the presence of heterogeneous skin tumors and wide inter- and intra-familial phenotypic variability. Histopathologically, both cylindromas and trichoepitheliomas were found in affected individuals. Mutations or loss of heterozygosity was not found in CYLD and PTCH genes. In CYLD and PTCH mutation negative patients, other genes may be affected and further studies are needed to clarify whether these patients may be affected by de novo germline mutations. PMID- 22077641 TI - Buonocore Memorial Lecture. AB - Abstract For many years, operative dentistry has been using regenerative approaches to treat dental disease. The use of calcium hydroxide to stimulate reparative or reactionary dentin is clearly an example of such a therapeutic strategy. The advent of tissue engineering is allowing dentistry to move forward in the use of regeneration as an underlying principle for the treatment of dental disease. Tissue engineering is a multi-disciplinary science that brings together biology, engineering and clinical sciences with developing new tissues and organs. It is based on fundamental principles that involve the identification of appropriate cells, the development of conducive scaffolds and an understanding of the morphogenic signals required to induce cells to regenerate the tissues that were lost. This review is focused on the presentation and discussion of existing literature that covers the engineering of enamel, dentin and pulp, as well on the engineering of entire teeth. There are clearly major roadblocks to overcome before such strategies move to the clinic and are used regularly to treat patients. However, existing evidence strongly suggests that the engineering of new dental structures to replace tissues lost during the process of caries or trauma will have a place in the future of operative dentistry. PMID- 22077642 TI - Highly sensitive high-pressure liquid chromatography with ultraviolet light method detected the reduction of serum nitrite/nitrate levels after cold exposure in patients with Raynaud's phenomenon. PMID- 22077644 TI - Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study. AB - OBJECTIVES: To examine the associations between serum homocysteine (tHcy), holotranscobalamin (holoTC, the biologically active fraction of vitamin B12) and folate and cognitive functioning in a longitudinal population-based study of Finnish elderly subjects. SUBJECTS AND DESIGN: tHcy, holoTC and folate were measured at baseline in 274 dementia-free subjects aged 65-79years from the Cardiovascular Risk Factors, Aging and Dementia study. Subjects were re-examined 7years later, and global cognition, episodic memory, executive functioning, verbal expression and psychomotor speed were assessed. RESULTS: Higher baseline tHcy levels were associated with poorer performance in global cognition, relative difference: 0.90 [95% confidence interval (CI) 0.81-0.99]; episodic memory: 0.87 (95% CI 0.77-0.99); executive functions: 0.86 (95% CI 0.75-0.98); and verbal expression: 0.89 (95% CI 0.81-0.97) at follow-up. Increased holoTC levels were related to better performance on global cognition: 1.09 (95% CI 1.00-1.19); executive functions: 1.11 (95% CI 1.01-1.21); and psychomotor speed: 1.13 (95% CI 1.01-1.26). After excluding 20 cases of incident dementia, increased tHcy remained associated with poorer performance in episodic memory, execution functions and verbal expression. Higher holoTC levels tended to be related to better performance in executive functions and psychomotor speed, while elevated serum folate concentrations were significantly related to higher scores in global cognition and verbal expression tests. CONCLUSIONS: tHcy, holoTC and folate levels are related to cognitive performance 7years later even in nondemented elderly subjects. Randomized trials are needed to determine the impact of vitamin B12 and folate supplementation on preventing cognitive decline in the elderly. PMID- 22077643 TI - Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness. AB - Some evidence suggests that the cerebellum participates in the complex network processing emotional facial expression. To evaluate the role of the cerebellum in recognising facial expressions we delivered transcranial direct current stimulation (tDCS) over the cerebellum and prefrontal cortex. A facial emotion recognition task was administered to 21 healthy subjects before and after cerebellar tDCS; we also tested subjects with a visual attention task and a visual analogue scale (VAS) for mood. Anodal and cathodal cerebellar tDCS both significantly enhanced sensory processing in response to negative facial expressions (anodal tDCS, p=.0021; cathodal tDCS, p=.018), but left positive emotion and neutral facial expressions unchanged (p>.05). tDCS over the right prefrontal cortex left facial expressions of both negative and positive emotion unchanged. These findings suggest that the cerebellum is specifically involved in processing facial expressions of negative emotion. PMID- 22077645 TI - 'We never expected this to happen': narratives of ageing with HIV among gay men living in London, UK. AB - The proportion of HIV-positive people over the age of 50 is rapidly increasing in the UK. This reflects the use of antiretroviral therapies and the transformation of HIV from life-threatening disease to chronic treatable illness. In this study a biographical narrative approach was used to explore the lived experience of ageing in 10 HIV-positive gay men aged between 50 and 78. While some participants regarded ageing as an opportunity to continue progressing towards valued life goals, others were more ambivalent about their future prospects. The findings suggest that these differences were particularly influenced by an individual's biographic relationship to the history of the HIV epidemic rather than chronological age. Those with long histories of involvement with HIV were more likely to be disadvantaged by careers interrupted by illness, to be dependent on state benefits and to have social networks damaged by multiple AIDS-related bereavements. The research identifies a cohort of older gay men likely to require additional support in adapting to the challenge of growing older with HIV. The article also explores the construction of moral identities in relation to discourses of 'successful ageing' and the possibility of building supportive communities that are sensitive to the needs of older gay men. PMID- 22077646 TI - Large-scale screening of mitochondrial DNA mutations among Iranian patients with prelingual nonsyndromic hearing impairment. AB - Hereditary hearing impairment (HI) is a genetically heterogeneous disorder caused by mutations either in nuclear DNA (nDNA) or in mitochondrial DNA (mtDNA). The nDNA mutations account for the majority of prelingual nonsyndromic HI (NSHI). The present survey was conducted to screen for known pathogenic mtDNA mutations including A1555G, A3243G, C1494T, and A7445G to provide an accurate estimate of their prevalence in prelingual NSHI for the first time in the Iranian subpopulations. One thousand unrelated probands with NSHI (including both GJB2 negative and GJB2 heterozygote cases) and 1000 healthy matched controls were investigated using the PCR/RFLP method followed by DNA sequencing to confirm the observed mtDNA mutations. Two of the studied mutations, namely A3243G and A7445G, were each found in a single family (a frequency of 0.1% for each). Mutation screening for A3243G followed by DNA sequencing led to the identification of G3316A substitution, with no prior link to HI. Surprisingly, screening for A3243G in the studied population identified 6 cases (0.6%) in probands and 10 (1%) in normal subjects. A1555G, the most common mtDNA mutation associated with deafness in other populations, was not found in the studied samples. To conclude, our findings indicate G3316A as a nonpathogenic variant in the prelingual NSHI subpopulations of Iran and suggest that mtDNA mutations do not play a major role in the etiology of NSHI in Iran. PMID- 22077647 TI - How to start research in general practice? Research workshop in Slovakia. PMID- 22077648 TI - Cancer risk in people with epilepsy using valproate-sodium. AB - OBJECTIVES: Based on reports of antitumour properties of sodium-valproate, we hypothesised that valproate has a cancer-protective effect in people with epilepsy. We aimed to determine cancer risk in people with epilepsy using sodium valproate. MATERIALS AND METHODS: Continuous data for 2997 people with epilepsy who had been prescribed valproate for at least two years, and for 11,988 unexposed people were provided by the UK General Practice Research Database. Hazard ratios (HRs) for all cancers and individual cancers between the exposed and unexposed groups, with smoking and alcohol consumption and age as covariates, were calculated using the Cox proportional hazards method. RESULTS: Exposure to valproate had no influence on the incidence of the composite of all cancers [HR: 1.19, 95% CI: 0.97-1.47, P = 0.10]; there was, however, a significant excess of colon cancers [HR: 3.95, 95% CI: 1.97-7.92, P = 0.001] and a trend towards an excess of prostate neoplasms [HR: 2.15, 95% CI: 0.92-5.02, P = 0.08] and in addition, a trend towards reduced incidence of breast cancer [HR: 0.40, 95% CI: 0.14-1.30, P = 0.08] in the exposed group. CONCLUSIONS: The lack of an inverse association between valproate use and hazard ratios for all cancers and several individual cancer sites does not lend support for a cancer-protective role for valproate. PMID- 22077657 TI - Angiographic findings of primary versus salvage varicoceles treated with selective gonadal vein embolization: an explanation for surgical treatment failure. AB - BACKGROUND AND PURPOSE: Gonadal vein angioembolization is a successful means of primary and salvage treatment for symptomatic varicoceles. We aim to investigate angiographic findings during embolization of primary varicoceles vs those with failed surgical ligation. PATIENTS AND METHODS: Between 1992 and 2010, 106 cases referred to our interventional radiologists for primary or salvage varicocelectomy were reviewed. These patients underwent venography and gonadal vein embolization using a combination of embolization coils and vascular plugs. All images were reviewed by an interventional radiologist to determine the anatomic etiology of the varicocele. Primary and salvage embolization cohorts were compared using t test and chi-square analyses for continuous and categorical variables, respectively. Angiographic parameters were analyzed using univariate and multivariable regression models to determine significance in predicting primary vs salvage status. RESULTS: Of the 106 patients, 46 patients (57 testicles) underwent primary and 60 patients (62 testicles) underwent salvage embolization. The salvage cohort of patients was younger (P<0.001) and comprised more solely left-sided pathology (P=0.002). An equivalent number of gonadal vein divisions and proportion of patent gonadal veins was found. However, there was a significantly higher proportion (27.8% vs 6.7%) of inguinal collateral vessels and combined presence of inguinal and retroperitoneal collateral veins (8.5% vs 2.1%) identified in the cohort undergoing embolization after failed surgical varicocelectomy. Presence of inguinal collaterals (P=0.008) as well as presence of both inguinal and retroperitoneal collaterals (P=0.038) on multivariable regression analysis revealed both as independent prognosticators of salvage status. CONCLUSION: Recurrence after surgical varicocelectomy is associated with increased inguinal collaterals. The pitfall presented by this anatomic variant to surgical ligation may be successfully managed with selective gonadal vein embolization. PMID- 22077658 TI - Anxiety and depression in obese and normal-weight individuals with diabetes type 2: a gender perspective. AB - BACKGROUND: Obesity is a problem that is increasing worldwide, leading to an increased incidence of type 2 diabetes mellitus (T2DM). Depression is more common among individuals with diabetes, and they are more likely than non-diabetic individuals to experience emotional problems. People with both T2DM and obesity bear an additional emotional burden, which affects their quality of life. OBJECTIVES: To describe the prevalence of symptoms of anxiety and depression in groups of obese and normal-weight individuals with T2DM who are undergoing primary care and to investigate possible differences between the groups and between genders. METHOD: Three hundred and thirty-nine patients with T2DM from nine primary-care centres participated in a cross-sectional study (n = 180 + 159). The response rate was 67%. The Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory - second edition (BDI-II) were employed to estimate the patients' symptoms of depression and anxiety. RESULTS: An association between T2DM, obesity and depression was observed in both genders. More than one in three women and one in five men with T2DM and obesity exhibited symptoms of anxiety or depression. In the normal-weight group, the females presented more symptoms of anxiety than did their male counterparts. CONCLUSION: In primary healthcare, the fact that both obese men and women with T2DM are at increased risk of anxiety and depression is an important finding, which must be recognised and considered in the course of primary healthcare consultations. Meeting the unique needs of each individual requires an understanding of both laboratory data and the individual's emotional status. PMID- 22077660 TI - Transrectal ultrasonography-guided biopsy does not reliably identify dominant cancer location in men with low-risk prostate cancer. AB - Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The widespread use of serum PSA testing followed by TRUS-guided biopsy have resulted in profound prostate cancer stage migration with many patients presenting with focal rather than multifocal disease. There is increasing interest in the use of focal rather than whole-gland treatment. However, current biopsy schemes may still miss cancer or, even when cancer is identified, its extent or grade might not be accurately characterized. In order for focal therapy to be effective, the area of highest tumour volume and/or grade needs to localized accurately. The aim of this study was to assess how well biopsy, as currently performed, locates the focus of highest prostate cancer volume and/or grade. OBJECTIVE: To evaluate the ability of transrectal ultrasonography (TRUS)-guided extended core biopsy to identify the dominant tumour accurately in men with early stage prostate cancer. PATIENTS AND METHODS: Patients with early stage, low-risk prostate cancer who subsequently underwent radical prostatectomy (RP) and had complete surgical specimens were identified. Re-review was performed by a single uropathologist using ImageJ software to identify tumour location, dominant grade (DG) and dominant volume (DV). Pathology findings were then compared with biopsy results. RESULTS: A total of 51 men with early stage, low-risk prostate cancer, who had undergone RP, had complete specimens for review and a median of 15 biopsy cores taken for diagnosis and grading. Sixteen men had a single diagnostic biopsy, 21 had one repeat biopsy, and 14 had two or more repeat biopsies. Compared with surgical findings, biopsy correctly identified the sextant with the largest tumour volume in 55% (95% CI 0.5-0.6) of specimens and the highest grade in 37% (95 CI 0.3-0.5). No demographic or clinical factors were significantly associated with identification of DG. Interval between last biopsy and RP, total tissue length taken and total length of tumour identified were significantly associated with correct identification of DV. CONCLUSIONS: Our findings show that TRUS-guided biopsy detects and localizes DV better than it does DG. Even with an extended scheme, TRUS-guided biopsy does not reliably identify dominant cancer location in this low-risk cohort of men with early stage prostate cancer. TRUS-guided biopsy may perform better in similar men with low stage, but higher volume disease. PMID- 22077659 TI - Proteome turnover in the green alga Ostreococcus tauri by time course 15N metabolic labeling mass spectrometry. AB - Protein synthesis and degradation determine the cellular levels of proteins, and their control hence enables organisms to respond to environmental change. Experimentally, these are little known proteome parameters; however, recently, SILAC-based mass spectrometry studies have begun to quantify turnover in the proteomes of cell lines, yeast, and animals. Here, we present a proteome-scale method to quantify turnover and calculate synthesis and degradation rate constants of individual proteins in autotrophic organisms such as algae and plants. The workflow is based on the automated analysis of partial stable isotope incorporation with (15)N. We applied it in a study of the unicellular pico-alga Ostreococcus tauri and observed high relative turnover in chloroplast-encoded ATPases (0.42-0.58% h(-1)), core photosystem II proteins (0.34-0.51% h(-1)), and RbcL (0.47% h(-1)), while nuclear-encoded RbcS2 is more stable (0.23% h(-1)). Mitochondrial targeted ATPases (0.14-0.16% h(-1)), photosystem antennae (0.09 0.14% h(-1)), and histones (0.07-0.1% h(-1)) were comparatively stable. The calculation of degradation and synthesis rate constants k(deg) and k(syn) confirms RbcL as the bulk contributor to overall protein turnover. This study performed over 144 h of incorporation reveals dynamics of protein complex subunits as well as isoforms targeted to different organelles. PMID- 22077663 TI - BRCA2 is a mediator of RAD51- and DMC1-facilitated homologous recombination in Arabidopsis thaliana. AB - * Mutations in the breast cancer susceptibility gene 2 (BRCA2) are correlated with hereditary breast cancer in humans. Studies have revealed that mammalian BRCA2 plays crucial roles in DNA repair. Therefore, we wished to define the role of the BRCA2 homologs in Arabidopsis in detail. * As Arabidopsis contains two functional BRCA2 homologs, an Atbrca2 double mutant was generated and analyzed with respect to hypersensitivity to genotoxic agents and recombination frequencies. Cytological studies addressing male and female meiosis were also conducted, and immunolocalization was performed in male meiotic prophase I. * The Atbrca2 double mutant showed hypersensitivity to the cross-linking agent mitomycin C and displayed a dramatic reduction in somatic homologous recombination frequency, especially after double-strand break induction. The loss of AtBRCA2 also led to severe defects in male meiosis and development of the female gametophyte and impeded proper localization of the synaptonemal complex protein AtZYP1 and the recombinases AtRAD51 and AtDMC1. * The results demonstrate that AtBRCA2 is important for both somatic and meiotic homologous recombination. We further show that AtBRCA2 is required for proper meiotic synapsis and mediates the recruitment of AtRAD51 and AtDMC1. Our results suggest that BRCA2 controls single-strand invasion steps during homologous recombination in plants. PMID- 22077664 TI - NF-kappaB signaling pathway is inhibited by heat shock independently of active transcription factor HSF1 and increased levels of inducible heat shock proteins. AB - NF-kappaB transcription factor regulates numerous genes important for inflammation, immune responses and cell survival. HSF1 is the primary transcription factor activated under stress conditions that is responsible for induction of genes encoding heat shock proteins. Previous studies have shown that the NF-kappaB activation pathway is blocked by heat shock possibly involving heat shock proteins. Here, we investigate whether active HSF1 inhibited this pathway in the absence of stress conditions. Activation of the NF-kappaB pathway and expression of NF-kappaB-dependent genes were analyzed in TNFalpha-stimulated U-2 OS human osteosarcoma cells that were either heat-shocked or engineered to express a constitutively active form of HSF1 in the absence of heat shock. As expected, heat shock resulted in a general blockade in the degradation of the IkappaBalpha inhibitor, nuclear translocation of NF-kappaB and expression of NF kappaB-dependent target genes. In marked contrast, the presence of constitutively active HSF1 did not block TNFalpha-induced activation of the NF-kappaB pathway or expression of a set of the NF-kappaB-dependent genes. We conclude that in the absence of heat shock, the NF-kappaB activation pathway is inhibited by neither active HSF1 transcription factor nor by increased levels of HSF1-induced heat shock proteins. PMID- 22077665 TI - Evaluation of the key aroma compounds in beef and pork vegetable gravies a la chef by stable isotope dilution assays and aroma recombination experiments. AB - Although the aroma compounds of meat processed as such have been studied previously, data on complete homemade dishes containing beef and pork meat were scarcely studied. Recently, 38 odor-active compounds were characterized in beef and pork vegetable gravies using GC-olfactometry. In the present investigation, the most odor-active compounds were quantitated in a freshly prepared stewed beef vegetable gravy (BVG) as well as a stewed pork vegetable gravy (PVG) by means of stable isotope dilution assays. Calculation of odor activity values (OAVs; ratio of concentration to odor threshold) revealed 3-mercapto-2-methylpentan-1-ol, (E,E)-2,4-decadienal, (E,Z)-2,6-nonadienal, (E)-2-decenal, (E)-2-undecanal, and 3 hydroxy-4,5-dimethyl-2(5H)-furanone as the most potent odorants in both gravies. However, significantly different OAVs were found for 12-methyltridecanal, which was much higher in the BVG, whereas (E,Z)-2,4-decadienal showed a clearly higher OAV in the PVG. Aroma recombination experiments performed on the basis of the actual concentrations of the odorants in both gravies revealed a good similarity of the aromas of both model mixtures containing all odorants with OAVs > 1 with those of the original gravies. PMID- 22077666 TI - Herpes simplex virus-induced plasmacytic atypia. AB - The clinical and histopathological features of cutaneous herpes simplex virus (HSV) infection have been well described. Genital herpetic infections are largely induced by HSV type 2, but 30% of cases can be caused by HSV type 1. Immunocompromised patients are known to exhibit atypical patterns of clinical presentation with variable lesion morphology and anatomic location. A subset of patients may show morphology such as nodules or verrucous lesions. Analogously, some biopsy specimens may show unusual microscopical features, such as a lack of keratinocyte cytopathology, lymphocyte infiltration or vasculopathic changes that are expected irrespective of the patient's immune status. We present the case of a patient carrying a previous diagnosis of pemphigus vulgaris, status posttreatment with methotrexate and prednisone, who developed a perineal ulcer exhibiting significant numbers of plasma cells, many of which were cytologically atypical. This morphology was suggestive of a hematopoietic malignancy. Immunoperoxidase staining for HSV decorated a focal collection of keratinocytes that lacked appreciable viral changes expected of HSV infection. PMID- 22077667 TI - The half-size ABC transporters STR1 and STR2 are indispensable for mycorrhizal arbuscule formation in rice. AB - The central structure of the symbiotic association between plants and arbuscular mycorrhizal (AM) fungi is the fungal arbuscule that delivers minerals to the plant. Our earlier transcriptome analyses identified two half-size ABCG transporters that displayed enhanced mRNA levels in mycorrhizal roots. We now show specific transcript accumulation in arbusculated cells of both genes during symbiosis. Presently, arbuscule-relevant factors from monocotyledons have not been reported. Mutation of either of the Oryza sativa (rice) ABCG transporters blocked arbuscule growth of different AM fungi at a small and stunted stage, recapitulating the phenotype of Medicago truncatula stunted arbuscule 1 and 2 (str1 and str2) mutants that are deficient in homologous ABCG genes. This phenotypic resemblance and phylogenetic analysis suggest functional conservation of STR1 and STR2 across the angiosperms. Malnutrition of the fungus underlying limited arbuscular growth was excluded by the absence of complementation of the str1 phenotype by wild-type nurse plants. Furthermore, plant AM signaling was found to be intact, as arbuscule-induced marker transcript accumulation was not affected in str1 mutants. Strigolactones have previously been hypothesized to operate as intracellular hyphal branching signals and possible substrates of STR1 and STR2. However, full arbuscule development in the strigolactone biosynthesis mutants d10 and d17 suggested strigolactones to be unlikely substrates of STR1/STR2. Interestingly, rice STR1 is associated with a cis-natural antisense transcript (antiSTR1). Analogous to STR1 and STR2, at the root cortex level, the antiSTR1 transcript is specifically detected in arbusculated cells, suggesting unexpected modes of STR1 regulation in rice. PMID- 22077668 TI - 'It [HIV] is part of the relationship': exploring communication among HIV serodiscordant couples in South Africa and Tanzania. AB - In many sub-Saharan African countries, a high proportion of people living with HIV are in long-term serodiscordant relationships. This paper explores how HIV serodiscordance shapes communication among couples in long-term HIV serodiscordant relationships. A total of 36 couples were purposively recruited through healthcare providers and civil society organisations in South Africa (26) and Tanzania (10). We explored couples' portrayal of living in a serodiscordant relationship by conducting semi-structured interviews with each partner separately, followed by a joint interview with both partners. Using an adaptation of Persson's model on sero-silence and sero-sharing, we categorised coping style as 'sero-silent' if partners reported that they did not talk much with each other about issues related to their serodiscordant status or as 'sero-sharing' if they portrayed HIV as being an issue which they dealt with together. Some couples exhibited features of both coping styles and, at times, partners differed in their ways of coping. PMID- 22077669 TI - Excisional biopsy for management of lateral tongue leukoplakia. AB - BACKGROUND: Leukoplakia of the lateral tongue is frequently associated with the risk of malignancy. Although incisional biopsy is accepted as a standard technique for evaluation, the possibility of underdiagnosis, and therefore missed diagnosis of malignancy, remains at all times. The aim of this study was to determine the rate of underdiagnosis by incisional biopsy for leukoplakia of the lateral tongue and to elucidate the underlying cause of for underdiagnosis. METHODS: Twenty-two patients with leukoplakia in the lateral tongue who had undergone excisional biopsy for suspicion of malignancy were included in the study. Pathology was reviewed and classified into 'no dysplasia,''dysplasia,' and 'carcinoma'. Underdiagnosis was defined as a change of diagnosis to a graver classification following excisional biopsy. To analyze the factors contributing to underdiagnosis, incisional and excisional biopsy specimens were re-evaluated. RESULTS: Of the 22 patients with leukoplakia of the lateral tongue, 59.1% had coexistent malignancy, including nine squamous cell carcinomas and four verrucous carcinomas. Incisional biopsy resulted in underdiagnosis in 73.3% of the cases. Underdiagnosis was attributable to three common errors, which were mis-selection of sampling site within a large area of leukoplakia, error in pathology specimen preparation owing to small specimen size, and superficial biopsy frequently associated with punch biopsy. CONCLUSION: Leukoplakia of the lateral tongue is highly coexistent with malignancy, and incisional biopsy frequently leads to underdiagnosis. Therefore, complete excision with adequate margin is warranted for leukoplakia of the lateral tongue, preferably under general anesthesia, which could be performed with minimal morbidity and function preservation. PMID- 22077670 TI - Comparison of anion removal capacities of Octolig and Cuprilig. AB - Mixtures of sodium salts of phosphate, arsenate, and fluoride were used in chromatography and batch experiments to compare the capacity of two immobilized ligands (IMLIGs) to remove these anions: Octolig and its copper (II)-based metallolig, Cuprilig. The focus of this study was twofold. First, to find out which material, Octolig or Cuprilig, would remove these anions most effectively; and secondly to determine the optimal capacity for removal of representative anions. Removal capacity was evaluated by two methods: by chromatography and by a batch method. The methods gave identical results, but the batch method was more convenient. Cuprilig had a lower capacity for removal of phosphate than Octolig. The capability of Octolig for removing anions was: phosphate > arsenate > fluoride >>> chloride >>>> bromide. Replication of phosphate removal was good for a given batch of Octolig. Of three different samples of Octolig, two seemed to be alike based on the phosphate- removal capacity; the third was different on the basis of a Student's t-test. This distinction indicates the batch procedure could serve as a quality control/assurance technique. PMID- 22077671 TI - Enhanced screening of glutathione-trapped reactive metabolites by in-source collision-induced dissociation and extraction of product ion using UHPLC-high resolution mass spectrometry. AB - A selective and sensitive approach, called extraction of product ion (XoPI) method, was developed for the detection of l-glutathione (GSH)-trapped reactive metabolites employing an Orbitrap high resolution mass spectrometer. Fragmentation of GSH conjugates in the negative ion mode leads to a product ion, deprotonated gamma-glutamyl-dehydroalanyl-glycine (m/z 272.0888). As a means of utilizing this property, negative ion high resolution MS data were collected from in vitro incubations by monitoring ions from m/z 269.5 to 274.5 under in-source collision-induced dissociation. Extraction of product ions at m/z 272.0888 +/- 5 ppm from this data resulted in a chromatogram exhibiting deprotonated gamma glutamyl-dehydroalanyl-glycine as the major peaks with no or very few interferences. Therefore, peaks in this extracted product ion chromatogram potentially came from GSH-trapped reactive metabolites. The GSH conjugate parent ions were then confirmed in the corresponding full scan MS data, and their structures were identified from their MS(2) fragmentation patterns. The effectiveness of the approach was assessed with four model compounds, amodiaquine, clozapine, diclofenac, and fipexide, all well-known to form GSH trapped reactive metabolites, following incubation in human liver microsomes supplemented with beta-nicotinamide adenine dinucleotide 2'-phosphate reduced tetrasodium salt (NADPH) and GSH. The results from XoPI method were compared to two other commonly employed liquid chromatography-mass spectrometry (LC-MS) methods: precursor ion scan method and mass defect filter method. Overall, the XoPI method was more selective and sensitive in detecting the GSH conjugates. Many GSH conjugates previously not reported were detected and characterized in this study. PMID- 22077677 TI - Use of anti-tumor necrosis factor-alpha therapy in hepatitis B virus carriers with psoriasis or psoriatic arthritis: a case series in Taiwan. AB - The use of anti-tumor necrosis factor (TNF)-alpha therapy in patients with psoriasis who are hepatitis B virus (HBV) carriers is usually not recommended, and routine antiviral prophylaxis is suggested for those who need the treatment. We report our experience on the safety of anti-TNF-alpha therapy in patients with psoriasis who are HBV carriers in our clinic using HBV viral load as a guide for HBV treatment. Between 2007 and 2011, seven HBV carriers receiving TNF-alpha inhibitors for psoriasis in our clinic were collected retrospectively. The HBV viral load and aminotransferase levels were regularly monitored. Two of the seven patients were inactive HBV carriers, and the other five patients had chronic hepatitis B. Only one patient received antiviral agents before the anti-TNF-alpha treatment. The mean duration of the anti-TNF-alpha treatment was 26.6 months (range, 14-45 months). These patients were followed up from the start of the anti TNF-alpha therapy for a mean duration of 28.9 months (range, 14-45 months). HBV reactivation was observed in three patients, one of whom required antiviral treatment. No HBV reactivation-related hepatitis was observed. In conclusion, prevention of HBV reactivation by monitoring of HBV viral load is cost-effective and may decrease the risk of developing drug resistance from routine anti-HBV prophylaxis treatment. It can be considered as an alternative in psoriasis patients treated by TNF-alpha inhibitors, especially in areas with a high HBV burden and in hepatitis B e-antigen-negative patients who have a lower risk of viral reactivation. PMID- 22077678 TI - Affective facilitation and inhibition of cultural influences on reasoning. AB - Research in South Korea and the United States examined how affective states facilitate or inhibit culturally dominant styles of reasoning. According to the affect-as-information hypothesis, affective cues of mood influence judgements by serving as embodied information about the value of accessible inclinations and cognitions. Extending this line of research to culture, we hypothesised that positive affect should promote (and negative affect should inhibit) culturally normative reasoning. The results of two studies of causal reasoning supported this hypothesis. Positive and negative affect functioned like "go" and "stop" signals, respectively, for culturally typical reasoning styles. Thus, in happy (compared to sad) moods, Koreans engaged in more holistic reasoning, whereas Americans engaged in more analytic reasoning. PMID- 22077679 TI - An appraisal and comparison of three methods of selecting patients for orthodontic treatment. AB - AIM: The selection of patients for orthodontic treatment is necessary where third party payment occurs. Selection can be based on one of several systems and in this report three methods are compared. METHODS: The examination was performed on a population of 790 Polish children with a mean age of 12 years and 2 months. In this report three methods of assessment are used. The authors' specific method relates malocclusion to the estimated risk of problems arising as a result of the malocclusion itself. The IOTN score system assesses the severity of different aspects of malocclusion, thus dividing patients into 5 groups. The DAL index quantifies the aesthetic appearance of the mouth. RESULTS: The results show that using our specific method, approximately 23% of patients should undergo treatment. The figure is approximately the same using the IOTN, though there is a slight difference in the actual patients chosen. The DAI results in an entirely different orthodontic treatment need. CONCLUSION: Our specific method is highly recommended. PMID- 22077680 TI - Halogen lamp and LED activation of resin-modified glass ionomer restorative material. In vitro microhardness after long-term storage. AB - AIM: The purpose of this study was to evaluate the activation of resin-modified glass ionomer restorative material (RMGI, Vitremer-3M-ESPE, A3) by halogen lamp (QTH) or light-emitting diode (LED) by Knoop microhardness (KHN) in two storage conditions: 24 hrs and 6 months and in two depths (0 and 2 mm). MATERIALS AND METHODS: The specimens were randomly divided into 3 experimental groups (n = 10) according to activation form and evaluated in depth after 24 h and after 6 months of storage. Activation was performed with QTH for 40s (700 mW/cm) and for 40 or 20 s with LED (1,200 mW/cm2). After 24 hrs and 6 months of storage at 37 degrees C in relative humidity in light-proof container, the Knoop microhardness test was performed. Statistics Data were analysed by three-way ANOVA and Tukey post-tests (p < 0.05). RESULTS: All evaluated factors showed significant differences (p < 0.05). After 24 hrs there were no differences within the experimental groups. KHN at 0 mm was significantly higher than 2 mm. After 6 months, there was an increase of microhardness values for all groups, being the ones activated by LED higher than the ones activated by QTH. CONCLUSION: Light-activation with LED positively influenced the KHN for RMGI evaluated after 6 months. PMID- 22077681 TI - Association between developmental enamel defects in the primary and permanent dentitions. AB - AIM: To determine if the presence of developmental enamel defects (DED) in the primary dentition is a risk indicator for the presence of DED in the permanent dentition in children with mixed dentition, as well as others factors. MATERIALS AND METHODS: A cross-sectional study was undertaken in 1296 school children ages six to 72 years. The DED [FDI; 1982] in both dentitions were identified by means of an oral exam scoring enamel opacities [classified as demarcated or diffused], and enamel hypoplasia. Sociodemographic and socioeconomic variables were collected through a questionnaire. Socioeconomic status (SES) was determined based on the occupation and maximum level of education of parents. Statistical analysis included logistic regression. RESULTS: Mean age of participants was 8.40 +/- 1.68; 51.6% were boys. DED prevalence was 7.5% in the permanent dentition and 10.0% in the primary dentition. The logistic regression model, adjusting for sociodemographic and socioeconomic variables, showed that for each primary tooth with DED, the odds of observing DED in the permanent dentition increased 7.38 times [95% CI = 1.17-1.64; p < 0.001]. CONCLUSION: An association between DED presence in both permanent and primary dentitions was observed. Further studies are necessary to fully characterise such relationship. PMID- 22077682 TI - Retrospective study on the occurrence of primary incisor trauma in preschool children of a low-income area in Brazil. AB - AIM: The objective of this study was to investigate the occurrence of trauma in primary incisors in a sample of preschool Brazilian children living in a low income area of Rio de Janeiro, Brazil. METHODS: For the study 527 dental records of a Municipal Children's Hospital were evaluated, and the following related factors were recorded: gender age, tooth affected, type and cause of trauma. Data were tabulated and subjected to statistical analysis (chi-square test). RESULTS: There were no significant differences in the prevalence of injuries among boys and girls. Children 10 to 24 months-old were the most affected (p < 0.05). The maxillary central incisor was the most affected tooth (p < 0.05), with predominance of lateral luxation and concussions (p > 0.05). The most common cause of trauma was associated with child's own-height fall (p < 0.05). CONCLUSION: Based on the results, it was concluded that the high incidence of incisor trauma in deciduous teeth should be viewed with concern, requiring the implementation of health policies aimed primarily at the prevention of such accidents. PMID- 22077683 TI - External apical root resorption caused by orthodontic treatment: a review of the literature. AB - AIM: External apical root resorption is a common consequence of orthodontic treatment. A number of treatment-related factors have been implicated in the pathogenesis of root resorption in orthodontic patients; however recent evidence suggests that genetic factors also play a major role in the development of this condition. Herein, we review prevalence, diagnosis and aetiology of root resorption with a particular emphasis on the effect of genetic variation and orthodontic forces, as well as discuss effective prevention strategies. PMID- 22077684 TI - Dental health education programme for 6-year-olds: a cluster randomised controlled trial. AB - AIM: Oral health is a reflection of general health and significantly influences the quality of life. Dental caries is one of the most common chronic diseases of childhood which may adversely affect physical, mental and social growth of children. Oral hygiene methods can effectively prevent oral and dental diseases, and oral hygiene education plays an important role in this regard. The aim of the present study was then to assess the effect of oral hygiene education on the oral and dental health of 6-year-olds. MATERIALS AND METHODS: A hundred and sixty 6 year-old children from 4 pre-school centers were divided into two groups, case and control, in this cluster randomised controlled trail. The children in the case group received oral and dental education in one session. The parents of the case group were also instructed in one session. The children and parents of the control group did not receive any instructions. Plaque index (PI): Turesky Gilmore-Glickman; gingival index (GI): Loe & Silness; at a) baseline, b) 1.5 and c) 6 months after the first examination. Data were analysed by repeated measure ANOVA. RESULTS: PI: A significant difference was found between the baseline examination and the first follow-up (p < 0.01), and between the baseline examination and the second follow-up (p < 0.001). GI: Although values in the case group were lower, no statistically significant difference was found between the two groups and within each group (p > 0.05). Regarding the number of brushing times, a statistically significant difference was found between the first and the second follow-ups of the study groups (p > 0.05). The brushing type and the application of other hygienic measures did not show any difference (p > 0.05). CONCLUSION: Within the limitations of the present study it may be concluded that oral hygiene instruction to 6-year-old children and their parents improves their dental health. PMID- 22077685 TI - Influence of posture on swallowing. AB - AIM: This study investigates the relationship between posture disorders and swallowing, either of infantile type or affected by the presence of a short lingual frenulum. MATERIALS AND METHODS: The stabilometry examinations, taking into account the Romberg index and the LFS value, and when needed a frenectomy, showed positive variations in the recovery of a proper posture. The data were analysed by means of the Wilcoxon signed-rank test. RESULTS AND CONCLUSION: This study showed that swallowing is able to modulate postural control and it can be a determining factor in postural syndromes that, if not promptly intercepted, may evolve into full-blown and irreversible musculoskeletal disorders for which treatment often proves ineffective. PMID- 22077686 TI - Incidence and distribution of deciduous molar ankylosis, a longitudinal study. AB - AIM: To study incidence and distribution of deciduous molar ankylosis. MATERIALS AND METHODS: study design: longitudinal retrospective study. A total of 512 consecutive subjects (aged 5 to 15 years) were examined at the Orthodontics and Paediatric Dentistry Department of the Genoa University School of Dentistry; for each subject an ortopantomography x-ray was taken. RESULTS: Thirty-four children were affected by deciduous molars ankylosis (6.6%). A statistically significant difference was revealed between the distributions: the lower deciduous molars were ankylosed more frequently than the upper ones (P < 0.001); the second deciduous molars were ankylosed more frequently than the first molars (P < 0.001). No statistical significance was found between sex and number of infraoccluded teeth (P = 0.74). CONCLUSION: This study found an incidence of deciduous molar ankylosis of about 6.6%; the lower deciduous molars and second deciduous molars were ankylosed more frequently (P < 0.001). PMID- 22077687 TI - Morphological characteristics of primary enamel surfaces versus permanent enamel surfaces: SEM digital analysis. AB - AIM: The morphology of permanent and primary enamel surface merits further analysis. The objective of this study was to illustrate a method of SEM digital image processing able to quantify and discriminate between the morphological characteristics of primary and permanent tooth enamel. METHODS: Sixteen extracted teeth, 8 primary teeth and 8 permanent teeth, kept in saline solution, were analysed. The teeth were observed under SEM. The SEM images were analysed by means of digitally processed algorithms. The two algorithms used were: Local standard deviation to measure surface roughness with the roughness index (RI); Hough's theorem to identify linear structures with the linear structure index (LSI). RESULTS: The SEM images of primary teeth enamel show smooth enamel with little areas of irregularity. No linear structures are apparent. The SEM images of permanent enamel show a not perfectly smooth surface; there are furrows and irregularities of variable depth and width. CONCLUSION: In the clinical practice a number of different situations require the removal of a thin layer of enamel. Only a good morphological knowledge of both permanent and primary tooth enamel gives the opportunity to identify and exploit the effects of rotary tools on enamel, thus allowing for a correct finishing technique. PMID- 22077688 TI - The dental age in the child with coeliac disease. AB - AIM: The coeliac disease deprives affected individual of the main nutritive factors, which are essential to promote body development: coeliac children are often subject to weight loss and have a lower somatic growth rate compared to healthy children. In addition, it is proven that prolonged malnutrition can have irreversible effects on dental eruption: teeth development also suffers a delay or it is slowed down in coeliac children. The purpose of this study was to evaluate and quantify the persistence of a delay in the dental age in children with coeliac disease and the presence of a possible constant relationship between the estimated delay in skeletal development and that referred to the dental age. MATERIALS AND METHODS: Seventy children (24 males and 46 females) were selected, all affected by coeliac disease, aged between 5.3 and 13.8 years, with a mean age of 9 years +/- 22 months SD. Through teleradiography of the skull in latero lateral projection and orthopantomography of the dental arches, the estimate of the skeletal development and dental age was carried out for each patient, applying two specific methods extensively described in the literature. RESULTS AND CONCLUSION: The results obtained, in agreement with the literature, show how the dental age, which is delayed in children affected by coeliac disease, may be considered as a reliable indicator of somatic growth and also of biological age. Furthermore, a gluten-free diet has considerable beneficial effects on skeletal development in relation to the dental age, in agreement with the hypothesis that dental development is controlled by different regulatory mechanisms, totally independent from those that influence skeletal development and the somatic and sexual development of the individual, even if the delay of dental development decreases progressively from the time of diagnosis of coeliac disease to introduction of a gluten-free diet. PMID- 22077689 TI - Treatment outcomes of pulpotomy in primary molars using two endodontic biomaterials. A 2-year randomised clinical trial. AB - AIM: To compare the treatment outcomes of calcium-enriched mixture (CEM) cement and mineral trioxide aggregate (MTA) as pulp dressing biomaterials in vital pulpotomy of carious primary molars. STUDY DESIGN: split-mouth randomised clinical trial. MATERIALS AND METHODS: Forty children aged 4-8 years with 2 carious teeth requiring pulpotomy were selected and randomly assigned to MTA (n = 40) or CEM (n = 40) groups. After coronal pulp removal, the remaining radicular pulp was covered with an appropriate biomaterial; the teeth were then permanently restored. Clinical/radiographic success/failures were blindly evaluated at 6-, 12 and 24-month follow-ups. STATISTICS: the recorded data were analyzed with McNemar test and GEE. RESULTS: A total of 36, 33 and 35 patients were available for 6-, 12- and 24-month follow-ups, respectively. At the 12-month follow-up only one and three teeth in the CEM and MTA groups had pathologic external root resorption, respectively. The resorbed teeth were then missed due to extraction/exfoliation at the 24-month follow-up; all other treated teeth were sign/symptom-free. Overall, clinical and radiographic outcomes in both MTA/CEM groups were comparable at the three follow-ups without significant differences. Time had no significant effect on the success. CONCLUSION: MTA and CEM demonstrated favourable treatment outcomes for pulpotomy of carious primary molars; CEM may be an effective pulp dressing biomaterial. PMID- 22077690 TI - Premature loss of maxillary primary incisor and delayed eruption of its successor: report of a case. AB - BACKGROUND: Traumatic injuries to primary teeth represent one of the most common aetiologic factors of time-related eruption disturbances of permanent teeth. These include premature eruption, delayed eruption or impactions. CASE REPORT: A case of a 7.5-year-old male with delayed eruption of the maxillary permanent left incisor is presented. The case history revealed a trauma around the age of 3 involving its primary tooth predecessor and its extraction by a dentist about one year later due to frequent abscesses. The clinical examination showed an early mixed dentition and the single presence of tooth 11 in the dental arch, with an obvious aesthetic problem that affected the child's self image. The periapical x ray ruled out any dimorphism on the impacted tooth, and it showed a root developed by two thirds. About 2 months after the examination, a simple gingivectomy was carried out, and the tooth could erupt completely 3 months later without any need for orthodontic traction. One year after surgery, a complete root development could be observed, as well as the presence of the lateral incisors with a moderate crowding. PMID- 22077691 TI - Crohn's disease of the mouth: report of a case. AB - AIM: Crohn's disease is a chronic, inflammatory process, probably immunologically mediated, that may affect any segment of the gastrointestinal tract from mouth to anus, usually in a discontinuous fashion. Oral manifestations are important clinical findings in Crohn's disease. CASE REPORT: Description of a young male with oral manifestations of Crohn's disease is detailed and the current literature is briefly reviewed. Past medical history and oral clinical examination of the patient were analysed. He was treated with systemic prednisone. The case reports a significant reduction of lesion after six months of treatment. PMID- 22077692 TI - Pre-hospital delays and intravenous thrombolysis in urban and rural areas. AB - INTRODUCTION: It is crucial to understand the reasons behind pre- and in-hospital delays to improve nationwide access to effective treatment for acute stroke. AIMS: To evaluate the pre- and in-hospital delays and to compare the intravenous (IV) thrombolysis rates in the urban and rural areas of the Province of Pomerania, Poland. MATERIALS & METHODS: We evaluated the medical records of 2134 patients treated in the stroke units (SUs) and consecutively reported to the Pomeranian Stroke Register from June 2006-December 2007. RESULTS: The time of ischaemic stroke onset was known in 488 (59%) of the 834 urban patients and in 744 (70%) of the 1063 rural patients (P < 0.001). The proportion of patients who called the emergency medical services with a delay of >45 min was similar in both locations: urban, 314/488 (64.3%) vs rural, 490/744 (65.8%). Although the proportion of patients who reached the emergency room within 3 h was higher in the rural areas (29.0% vs 24.3%; P = 0.02), only 4.2% of these patients received IV thrombolysis compared with 23.1% in the urban areas (P < 0.001). The proportion of patients who did not seek any kind of professional medical help prior to admission was lower in the rural areas (29/744 (3.9%) vs urban 50/488 (10.2%)) (P < 0.001). CONCLUSIONS: Pre-hospital delays reduced the number of patients eligible for IV thrombolysis in both rural and urban areas. The low proportion of patients treated with IV thrombolysis in rural SUs may be attributed to ineffective in-hospital procedures. PMID- 22077693 TI - Surgical and oncologic outcomes of laparoscopic partial nephrectomy: a Japanese multi-institutional study of 1375 patients. AB - BACKGROUND AND PURPOSE: Despite clear trends toward minimally invasive surgery, information about laparoscopic partial nephrectomy (LPN) in Japan is sparse. We conducted a retrospective survey to clarify time trends for LPN and analyze surgical and oncologic outcomes. PATIENTS AND METHODS: A nationwide survey was performed. Between 1998 and 2008, 1375 patients underwent LPN at 54 institutions. Complications, patterns of tumor recurrence, and recurrence-free survival were analyzed. RESULTS: Renal pedicle clamping was used in 1031 (75%) cases, and renal cooling was performed in 64%. Median warm/cold ischemic time was 37/53 minutes. Median tumor size was 2.26 cm (interquartile range 1.6 to 2.7). Multivariate analysis identified total operative time, operative blood loss, and surgical margin status as independently associated with high grade (grade 3-5) urologic and nonurologic complications. Despite increases in central tumor, a trend was seen toward shorter warm/cold ischemic time in recent cases, and the overall complication rate did not change throughout the study period. With a median follow-up of 26 months for 1193 malignancies, recurrence occurred in 22 (1.7%) patients, including local recurrence in 7 (0.5%), lung in 8 (0.7%), lymph nodes in 2 (0.1%), and bone in 4 (0.3%). Of the 26 cases with positive surgical margins, local tumor recurrence occurred in only one. CONCLUSIONS: This is the first nationwide survey of LPN in Japan to be reported. LPN could be performed with acceptable positive margins and complication rates. Most tumor recurrences occur as metastases, and surgical margin status appears to have little impact on oncologic outcomes. PMID- 22077694 TI - Evaluation of GSTP1 and APC methylation as indicators for repeat biopsy in a high risk cohort of men with negative initial prostate biopsies. AB - Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Hypermethylation of genes such as glutathione-S-transferase P1 (GSTP1) and adenomatous polyposis coli (APC) occurs with high frequency in prostate tumour tissue but is much less common in the benign prostate; however, the potential value of gene methylation biomarkers as an adjunct to biopsy histopathology has had little study. When measured in histologically benign prostate biopsy tissue, APC gene hypermethylation was found to have high negative predictive value and high sensitivity. GSTP1 hypermethylation was found to have lower performance than APC. OBJECTIVE: To evaluate the performance of DNA methylation biomarkers in the setting of repeat biopsy in men with an initially negative prostate biopsy but a high index of suspicion for missed prostate cancer. PATIENTS AND METHODS: We prospectively evaluated 86 men with an initial histologically negative prostate biopsy and high risk features. All men underwent repeat 12-core ultrasonography-guided biopsy. DNA methylation of glutathione-S-transferase P1 (GSTP1) and adenomatous polyposis coli (APC) was determined using tissue from the initially negative biopsy and compared with histology of the repeat biopsy. The primary outcome was the relative negative predictive value (NPV) of APC compared with GSTP1, and its 95% confidence interval (CI). RESULTS: On repeat biopsy, 21/86 (24%) men had prostate cancer. APC and GSTP1 methylation ratios below the threshold (predicting no cancer) produced a NPV of 0.96 and 0.80, respectively. The relative NPV was 1.2 (95% CI: 1.06-1.36), indicating APC has significantly higher NPV. Methylation ratios above the threshold yielded a sensitivity of 0.95 for APC and 0.43 for GSTP1. Combining both methylation markers produced a performance similar to that of APC alone. APC methylation patterns were consistent with a possible field effect or occurrence early in carcinogenesis. CONCLUSIONS: APC methylation provided a very high NPV with a low percentage of false-negatives, in the first prospective study to evaluate performance of DNA methylation markers in a clinical cohort of men undergoing repeat biopsy. The potential of APC methylation to reduce unnecessary repeat biopsies warrants validation in a larger prospective cohort. PMID- 22077695 TI - Accuracy and precision of the Pediatric Evaluation of Disability Inventory computer-adaptive tests (PEDI-CAT). AB - AIM: The aims of the study were to: (1) build new item banks for a revised version of the Pediatric Evaluation of Disability Inventory (PEDI) with four content domains: daily activities, mobility, social/cognitive, and responsibility; and (2) use post-hoc simulations based on the combined normative and disability calibration samples to assess the accuracy and precision of the PEDI computer-adaptive tests (PEDI-CAT) compared with the administration of all items. METHOD: Parents of typically developing children (n = 2205) and parents of children and adolescents with disabilities (n = 703) between the ages of 0 and 21 years, stratified by age and sex, participated by responding to PEDI-CAT surveys through an existing Internet opt-in survey panel in the USA and by computer tablets in clinical sites. RESULTS: Confirmatory factor analyses supported four unidimensional content domains. Scores using the real data post hoc demonstrated excellent accuracy (intraclass correlation coefficients >= 0.95) with the full item banks. Simulations using item parameter estimates demonstrated relatively small bias in the 10-item and 15-item CAT versions; error was generally higher at the scale extremes. INTERPRETATION: These results suggest the PEDI-CAT can be an accurate and precise assessment of children's daily performance at all functional levels. PMID- 22077697 TI - Roles of cocaine- and amphetamine-regulated transcript in the central nervous system. AB - 1. Cocaine- and amphetamine-regulated transcript (CART), first isolated from the ovine hypothalamus, is a potential neurotransmitter widely distributed throughout the central and peripheral nervous systems, as well as in endocrine cells in the pituitary and adrenal glands, pancreatic islets and stomach. 2. Numerous studies have established the role of CART in food intake, maintenance of bodyweight, stress control, reward and pain transmission. Recently, it was demonstrated that CART, as a neurotrophic peptide, had a cerebroprotective against focal ischaemic stroke and inhibited the neurotoxicity of beta-amyloid protein, which focused attention on the role of CART in the central nervous system (CNS) and neurological diseases. 3. In fact, little is known about the way in which CART peptide interacts with its receptors, initiates downstream cascades and finally exerts its neuroprotective effect under normal or pathological conditions. The literature indicates that there are many factors, such as regulation of the immunological system and protection against energy failure, that may be involved in the cerebroprotection afforded by CART. 4. The present review provides a brief summary of the current literature on CART synthesis and active fragments, its distribution in the CNS and, in particular, the role of CART peptide (and its receptors and signalling) in neurological diseases. PMID- 22077696 TI - The formamidopyrimidines: purine lesions formed in competition with 8-oxopurines from oxidative stress. AB - DNA is constantly exposed to agents that induce structural damage, from sources both internal and external to an organism. Endogenous species, such as oxidizing chemicals, and exogenous agents, such as ultraviolet rays in sunlight, together produce more than 70 distinct chemical modifications of native nucleotides. Of these, about 15 of the lesions have been detected in cellular DNA. This kind of structural DNA damage can be cytotoxic, carcinogenic, or both and is being linked to an increasingly lengthy list of diseases. The formamidopyrimidine (Fapy) lesions are a family of DNA lesions that result after purines undergo oxidative stress. The Fapy lesions are produced in yields comparable to the 8-oxopurines, which, owing in part to a perception of mutagenicity in some quarters, have been subjected to intense research scrutiny. But despite the comparable abundance of the formamidopyrimidines and the 8-oxopurines, until recently very little was known about the effects of Fapy lesions on biochemical processes involving DNA or on the structure and stability of the genomic material. In this Account, we discuss the detection of Fapy lesions in DNA and the mechanism proposed for their formation. We also describe methods for the chemical synthesis of oligonucleotides containing Fapy.dA or Fapy.dG and the outcomes of chemical and biochemical studies utilizing these compounds. These experiments reveal that the formamidopyrimidines decrease the fidelity of polymerases and are substrates for DNA repair enzymes. The mutation frequency of Fapy.dG in mammals is even greater than that of 8-oxodGuo (8-oxo-7,8-dihydro-2'-deoxyguanosine, one of the 8 oxopurines), suggesting that this lesion could be a useful biomarker and biologically significant. Despite clear similarities, the formamidopyrimidines have lived in the shadow of the corresponding 8-oxopurine lesions. But the recent development of methods for synthesizing oligonucleotides containing Fapy.dA or Fapy.dG has accelerated research on these lesions, revealing that the formamidopyrimidines are repaired as efficiently and, in some cases, more rapidly than the 8-oxopurines. Fapy.dG appears to be a lesion of biochemical consequence, and further study of its mutagenicity, repair, and interactions with DNA structure will better define the cellular details involving this important product of DNA stress. PMID- 22077698 TI - Evaluation of online miRNA resources for biomedical applications. AB - MicroRNAs (miRNAs) are endogenous single-stranded, 22-nt (nucleotide) RNAs which complement mRNA to initiate post-transcriptional regulation. This review presents updates and evaluations of the public domain resources available for miRNA identification and target prediction toward their utilization in the biomedical research approach. This study discusses the basic principles of miRNA computational studies based on the nature and mechanism of action of miRNAs. Furthermore, we have explored fifty-nine current online miRNA tools that can be categorized into three classes in this paper: (i) miRNA identification; (ii) miRNA target prediction; and (iii) specialized miRNA tools. PMID- 22077699 TI - The school nursing profession in relation to Bourdieu's concepts of capital, habitus and field. AB - AIM: The aim was to define the work and professional role of school nurses, in terms of Bourdieu's key concepts of capital and habitus. METHOD: A qualitative study with a deductive approach, based on data from six focus-group interviews with 24 school nurses and 15 individual interviews with school nurses. Thus, a total of 39 school nurses participated in the study. The data were analysed using content analysis. RESULTS: The results explain, in terms of Bourdieu's key concepts of capital and habitus, how school nurses experience their work in the educational setting. A model including different aspects of school nurses' work is shown. CONCLUSION: The new Swedish Education Act focuses on promoting students' general health, so that they are able to reach their academic potential. In this task, the school nurse is to be one of a group of several professionals working together. The present study shows how school nurses experience their professional role and their work in relation to Bourdieu's concepts of capital, habitus and field. To strengthen the school nursing profession, school nurses need to show their competence in promoting students' health. PMID- 22077700 TI - Opportunities taken: the need for and effectiveness of secondary care opportunistic immunisation. AB - AIM: To evaluate the effectiveness of a formalised opportunistic immunisation (OI) system in a hospital setting. METHODS: Pre-post implementation audit of missed immunisation opportunities. RESULTS: Of 5583 children in the National Immunisation Register cohort seen in a hospital setting, 1641 (29.4%) were under immunised, compared with the concurrent regional cohort of 15%. Maori children were less likely to be age-appropriately immunised (36.9% under-immunised, P < 0.0005, chi(2) = 41.4). Of the 1641 under-immunised children, 337 (20.5%) were deemed to have current medical reasons not to be immunised acutely, and of the remaining 1304, 244 (18.7%) declined immunisations. This left 1060 for whom immunisation was possible, and we immunised 880 (83.0%) of these. All children were re-engaged with primary care services. CONCLUSIONS: Children in contact with secondary care services have low immunisation rates with ethnic disparity. Appropriately resourced formalised OI is effective, with potential for further improvement. The system we have implemented enhances primary care involvement. PMID- 22077701 TI - DNA fingerprinting and new tools for fine-scale discrimination of Arabidopsis thaliana accessions. AB - One of the main strengths of Arabidopsis thaliana as a model species is the impressive number of public resources available to the scientific community. Exploring species genetic diversity--and therefore adaptation--relies on collections of individuals from natural populations taken from diverse environments. Nevertheless, due to a few mislabeling events or genotype mixtures, some variants available in stock centers have been misidentified, causing inconsistencies and limiting the potential of genetic analyses. To improve the identification of natural accessions, we genotyped 1311 seed stocks from our Versailles Arabidopsis Stock Center and from other collections to determine their molecular profiles at 341 single nucleotide polymorphism markers. These profiles were used to compare genotypes at both the intra- and inter-accession levels. We confirmed previously described inconsistencies and revealed new ones, and suggest likely identities for accessions whose lineage had been lost. We also developed two new tools: a minimal fingerprint computation to quickly verify the identity of an accession, and an optimized marker set to assist in the identification of unknown or mixed accessions. These tools are available on a dedicated web interface called ANATool (https://www.versailles.inra.fr/ijpb/crb/anatool) that provides a simple and efficient means to verify or determine the identity of A. thaliana accessions in any laboratory, without the need for any specific or expensive technology. PMID- 22077703 TI - Use of potassium iodide (KI) in a nuclear emergency. PMID- 22077704 TI - Economic motives for family limitation. AB - Abstract Taiwan can boast one of the most rapid rates of economic development in the world over the past 20 years. Taiwan is also in the midst of the demographic transition. The nature of the connection between economic development and the onset and progress of the fertility decline is far from clear, however. Rather than explore the relation between income and fertility change, this paper will be concerned with some of the economic motivations which may be responsible for fertility decline during the demographic transition. Inquiries in this area have been handicapped by having to rely on aggregative or on household data which included only a very limited set of economic variables (other than income) along with demographic data. In order to re-examine the linkages between economic change and fertility change at the family level, a special survey was conducted in Taiwan in 1969. While recognizing that economic factors are not wholly, perhaps not even primarily, responsible for the lowering of the birth rate, the central interest of this paper is the complex of cost and benefit considerations which may contribute to a decline of the rate, using the new data for Taiwan. PMID- 22077705 TI - Fertility effects of the abolition of legal abortion in Romania. AB - Abstract There is much interest to-day in governmental actions and regulations designed to have an effect on fertility. Widespread concern with the implications of population growth has led to unprecedented attention to the design and implementation of governmental policies intended to affect fertility. Unfortunately, there is very little empirical evidence of the effect of governmental action, largely because of the difficulty of interpreting the causal relations between changes in laws or programmes on the one hand, and fertility trends on the other. For this reason, the drastic alteration of the fertility laws in Romania in 1966 is of special interest in that it provides something approaching an experimental context for examining the effect of a legal code on fertility. PMID- 22077706 TI - The influence of labour force participation and education on fertility in Thailand. AB - Abstract Increasingly, discussion of the appropriateness and effectiveness of methods to limit population growth have focussed both on measures which seek to provide new and efficient contraceptives to an ever larger target population and on those measures which go beyond family planning to emphasize the need for adoption of policies 'expressly related to family roles and opportunities for legitimate alternative satisfactions and activities'.(1) Proponents of the latter course of action argur that such policies offer greater promise of reduction in family size because they directly assault the motivational framework of reproduction. Among the means suggested for limiting reproductioe within marriage as well as postponing marriage is modification of the complementarity of the rolen of men and women.(2) Of particular interest in this regard is the nature of the relation betweens female labour force participation and education and fertility, and the implications these relations may have for future fertility reduction, particularly in the developing world. PMID- 22077707 TI - Implications of selective feedback in aspects of family planning research for policy-makers in India. AB - Abstract Research and evaluation on any programme of the size and complexity of India's family planning programme provide essential feedback of information for policy-makers. In India's case the volume of feedback is very large (a cumulative total of about 300 KAP studies from the early fifties is reported). The methodology, utility and comparability of such studies have already attracted criticism.(1) In this article I hope to show that, in spite of an 'information overload' from KAP, communication, and evaluation studies (the aspects of family planning research considered here), the feedback is overwhelmingly selective in many important respects, leading to an unbalanced and unduly optimistic basis for further direction of the programme. PMID- 22077708 TI - Recent fertility decline in Ceylon. AB - Abstract The crude birth rate for Ceylon has been falling steadily between 1960 and 1970, except for a slight interruption in 1968. The fall between 1953 and 1963 has been documented elsewhere and this paper will therefore deal with the period 1963-69. PMID- 22077709 TI - Social and economic factors in Hong Kong's fertility decline. AB - Abstract In both developed and underdeveloped areas, many attempts have been made to alter the course of fertility through family planning intervention. Doubtless the availability of such services facilitates birth control for those who already desire to use it. Whether or not such exogenous interventions have any independent effect upon the operation of endogenous forces in the economy and society is, however, more problematical. Where fertility declines have been observed, family planning services have often been made widely available only after the decline in fertility had already set in. Nonetheless, observers have often attempted to attribute some fraction of the continuing decline in fertility to the operation of family planning activities. One especially notable case is that of Hong Kong, which provides some of the more persuasive evidence about the independent effects of family planning intervention. PMID- 22077710 TI - The integrative potential of a fertility model: An analytical test. AB - Abstract In an earlier paper a working model of marital fertility was presented.(1) That model grew out of a close study of Becker's economic model for fertility analysis.(2) Becker's model was modified in several respects in order to meet a number of major objections levelled against it by Judith Blake, Deborah Freedman, and others.(3) The purpose of the present paper is to examine how far the model presented earlier can serve as a 'binder' for the interpretative schemes now available in the literature on fertility differentials. More specifically, the objective is to identify the underlying explanatory factors of a number of analytical hypotheses concerning fertility differentials, and to examine whether the factors thus identified can be located in the fertility model presented in the earlier paper.(4) Little attention will be paid to the causal directions, if any, recognized in the hypotheses studied, nor will we attempt to provide a systematic review of empirical findings. PMID- 22077711 TI - 'Continuation rate', 'use-effectiveness' and their assessment for the diaphragm and jelly method. AB - Abstract The application of the life-table technique in the calculation of use effectiveness of a contraceptive was proposed by Potter in 1963.(1) The technique was also found to be useful in assessing the duration for which the use of a contraceptive was continued. The keen interest that existed in the use of IUD in the mid-1960's was reflected in the terminology developed for assessment of the continuity of use. 'Retention rate' was a frequently used index.(2) Because of the development of the concept of segments whose end-period determined either termination of the use of a method or its continuance on a cut-off date, 'closure rate' and 'termination rate' have been used as measures of the discontinuance of the use of methods primarily of the IUD.(3) While discussing concepts relating to acceptance, use and effectiveness of family planning methods, more generally, an expert group suggested that 'continuation' should be used to denote that a client (or a couple) had begun to practise a method and that the method was still being practised.(4) Since this group defined 'an acceptor' as a person taking service and/or advice, i.e. having an IUD insertion or a sterilization operation or receiving supplies (or advice on methods such as 'rhythm' or coitus-interruptus with the intent of using the method), the base for the assessment of continuation rates, according to this group, would be only those acceptors who had begun using the method. The lifetable method has also been used for the study of the continuation rate for pill acceptors.(5) Balakrishnan, et al., made a study of continuation rates of oral contraceptives using the multiple decrement life-table technique.(6). PMID- 22077712 TI - Some problems in the use of open birth intervals as indicators of fertility change. AB - Abstract To measure changes in fertility brought about by specific family planning programmes has been one of the problems faced by demographers as well as policy-makers. This problem is particularly difficult in developing countries where the basic data are poor. Hence, there is a need to find indices of fertility that are easy to obtain, sensitive to changes in fertility and either not grossly affected by errors in data, or alternatively amenable to correction of data errors. Among many possible indices, the open live birth interval has attracted attention of many researchers and experts.(1). PMID- 22077713 TI - The time response in averted births. AB - Abstract A calculation of the timing of births that are averted may seem a curious exercise, when not only do the births in question not occur, but the corresponding conceptions may never have existed. However, such a calculation may have considerable use. In order to assess the likely direct impact of a contraceptive programme on birth rates it is useful to estimate the number of births that would, in the absence of the programme, have occurred among the couples who accept it. Moreover, some time would necessarily elapse before a new 'steady state' in fertility could be reached, even if the programme and the potentially fertile population did not change in any way; and it is worth while to seek to find the times (for a few years after the start of a programme) when the (averted) births would have occurred in its absence, and to examine any inherent oscillations produced in birth rates by it. This question is considered below only for groups of women aged 20 at marriage (a state which is taken to be the start of regular exposure to the risk of conception), but the same methods are applicable to other ages, (possibly allowing for mortality) and appropriate combinations of age groups and cohorts in the fertile range may be used to estimate changes in fertility and reproduction rates expected from a programme, subject to given conditions, for several years after its start. The methods can also be generalised, by means of convolution, to contraceptive programmes that change with time, but these are not considered further. PMID- 22077716 TI - Feelings of regret following uncommitted sexual encounters in Canadian university students. AB - In this study we explored the prevalence of regret following uncommitted sexual encounters (i.e., casual sex that occurs with someone once and only once or with someone known for less than 24 hours) among 138 female and 62 male Canadian university students, who were approximately 21 years of age. The majority of participants self-reported that they had experienced feelings of regret after an uncommitted sexual encounter. We found women reported feeling significantly more regret than men. However, men's regret was more closely tied to physical attributes than women's regrets. Regret was also influenced by the quality of the sex: high-quality sex rarely led to regret, while the reverse was true for poor quality sex. In keeping with past studies, intoxication by alcohol and/or drugs was often listed as a source of regret by both men and women. PMID- 22077717 TI - Qualitative and quantitative MALDI imaging of the positron emission tomography ligands raclopride (a D2 dopamine antagonist) and SCH 23390 (a D1 dopamine antagonist) in rat brain tissue sections using a solvent-free dry matrix application method. AB - The distributions of positron emission tomography (PET) ligands in rat brain tissue sections were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). The detection of the PET ligands was possible following the use of a solvent-free dry MALDI matrix application method employing finely ground dry alpha-cyano-4-hydroxycinnamic acid (CHCA). The D2 dopamine receptor antagonist 3,5-dichloro-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}-2 hydroxy-6-methoxybenzamide (raclopride) and the D1 dopamine receptor antagonist 7 chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol (SCH 23390) were both detected at decreasing abundance at increasing period postdosing. Confirmation of the compound identifications and distributions was achieved by a combination of mass-to-charge ratio accurate mass, isotope distribution, and MS/MS fragmentation imaging directly from tissue sections (performed using MALDI TOF/TOF, MALDI q-TOF, and 12T MALDI-FT-ICR mass spectrometers). Quantitative data was obtained by comparing signal abundances from tissues to those obtained from quantitation control spots of the target compound applied to adjacent vehicle control tissue sections (analyzed during the same experiment). Following a single intravenous dose of raclopride (7.5 mg/kg), an average tissue concentration of approximately 60 nM was detected compared to 15 nM when the drug was dosed at 2 mg/kg, indicating a linear response between dose and detected abundance. SCH 23390 was established to have an average tissue concentration of approximately 15 MUM following a single intravenous dose at 5 mg/kg. Both target compounds were also detected in kidney tissue sections when employing the same MSI methodology. This study illustrates that a MSI may well be readily applied to PET ligand research development when using a solvent-free dry matrix coating. PMID- 22077718 TI - Emerging concepts on the role of innate immunity in the prevention and control of HIV infection. AB - While neutralizing antibodies can provide sterilizing protection from HIV infection via their variable domains, the antibody constant domain provides a functional link between innate and adaptive immunity and offers a means to harness the potent antiviral properties of a wide spectrum of innate immune effector cells. There has been a growing appreciation of the role of these effector mechanisms across fields from cancer immunotherapy to autoimmunity and infectious disease, as well as speculation that this mechanism may be responsible for the protection observed in the RV144 HIV vaccine trial. This review summarizes these extraneutralizing humoral immune activities, progress in defining the importance of these effector mechanisms during progression in HIV infection, and the potential impact that such vaccine-induced immune responses may have on protection from infection. PMID- 22077721 TI - A collection of robust organic synthesis reactions for in silico molecule design. AB - A focused collection of organic synthesis reactions for computer-based molecule construction is presented. It is inspired by real-world chemistry and has been compiled in close collaboration with medicinal chemists to achieve high practical relevance. Virtual molecules assembled from existing starting material connected by these reactions are supposed to have an enhanced chance to be amenable to real chemical synthesis. About 50% of the reactions in the dataset are ring-forming reactions, which fosters the assembly of novel ring systems and innovative chemotypes. A comparison with a recent survey of the reactions used in early drug discovery revealed considerable overlaps with the collection presented here. The dataset is available encoded as computer-readable Reaction SMARTS expressions from the Supporting Information presented for this paper. PMID- 22077719 TI - Vaccines for malaria: how close are we? AB - Vaccines are the most powerful public health tools mankind has created, but malaria parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines. Despite decades of research toward a vaccine for malaria, this goal has remained elusive. Nevertheless, recent advances justify optimism that a licensed malaria vaccine is within reach. A subunit recombinant protein vaccine that affords in the neighborhood of 50% protective efficacy against clinical malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a highly efficacious malaria vaccine that would improve prospects for malaria eradication may lie with the use of attenuated whole parasites and powerful immune-boosting adjuvants. PMID- 22077722 TI - Localized granulation tissue-like nodules: an unusual cutaneous presentation of secondary syphilis. PMID- 22077723 TI - Test-retest reliability of an emotion maintenance task. AB - Research on working memory has suggested domain-specific components for visual, verbal, and spatial information, and more recently for emotion. Affective working memory has been proposed as the set of processes involved in the maintenance of emotions to guide behaviour. The current study examined the reliability of an emotion maintenance/affective working memory task over two experimental sessions separated by one week. Subjective accuracy based on individual ratings was found to correlate over time and was highest for negatively valenced pictures. Results suggest that this paradigm is a reliable measure of emotion maintenance, underscoring the utility of this measure as an assessment tool for normative and clinical populations. PMID- 22077724 TI - An assessment of transgenomics as a tool for identifying genes involved in the evolutionary differentiation of closely related plant species. AB - * Transgenomics is the process of introducing genomic clones from a donor species into a recipient species and then screening the resultant transgenic lines for phenotypes of interest. This method might allow us to find genes involved in the evolution of phenotypic differences between species as well as genes that have the potential to contribute to reproductive isolation: potential speciation genes. * More than 1100 20-kbp genomic clones from Leavenworthia alabamica were moved into Arabidopsis thaliana by transformation. After screening a single primary transformant for each line, clones associated with mutant phenotypes were tested for repeatability and co-segregation. * We found 84 clones with possible phenotypic effects, of which eight were repeatedly associated with the same phenotype. One clone, 11_11B, co-segregated with a short fruit phenotype. Further study showed that 11_11B affects seed development, with as much as one-third of the seeds aborted in some fruit. * Transgenomics is a viable strategy for discovering genes of evolutionary interest. We identify methods to reduce false positives and false negatives in the future. 11_11B can be viewed as a potential speciation gene, illustrating the value of transgenomics for studying the molecular basis of reproductive isolation. PMID- 22077725 TI - Effects of estrogen metabolite 2-methoxyestradiol on tumor suppressor protein p53 and proliferation of breast cancer cells. AB - An endogenous 17beta-estradiol (E(2)) metabolite, 2-methoxyestradiol (2-ME(2)), has been reported to exhibit estrogen receptor (ER)-independent anti-angiogenic and anti-tumor effects. Several mechanisms have been proposed for 2-ME(2) actions, but there is a lack of evidence for a common pathway for all of the cell types sensitive to this metabolite. We have examined potential alterations in p53 in response to 2-ME(2), E(2) and the microtubule disruptor taxol in T47D breast cancer cells. Cells were cultured for six days in medium depleted of endogenous steroids or effectors. Semi-confluent cells were treated with 2-ME(2) (1 nM - 10 uM), 10 nM E(2) and/or 1 uM taxol and subjected to SDS-PAGE and Western blot analysis, quantitative analysis, or laser-scanning confocal microscopy. Western blot analysis revealed a concentration-dependent biphasic trend in p53 levels. Addition of 10 nM - 1 uM 2-ME(2) induced significant up-regulation in p53, and this response gradually diminished to levels comparable to the control upon treatment with higher concentrations (2.5 - 10 uM). The observed upregulation of p53 induced by 2-ME(2) is inhibited by concurrent treatment with 1 uM taxol. Cell quantitation revealed a significant decrease (50 - 90%) in cell number upon treatment with 1 - 10 uM 2-ME(2) with minimal effect at lower concentrations. No additional effect on cell proliferation was observed when taxol was combined with 10 nM or 1 uM 2-ME(2). In a concentration dependent manner, treatment with 2 ME(2) for 24 h differentially influenced cellular localization of p53. These results may aid in further understanding the relationship between steroid receptors, tumor suppressor proteins, and effects of hormone metabolites on breast cancer cells. PMID- 22077726 TI - Autonomic dysfunction in ischemic stroke with carotid stenosis. AB - OBJECTIVES: Impaired autonomic function is common in acute ischemic stroke. Previous limited studies have suggested that atherosclerosis may affect the distensibility of the carotid sinus and then impair the cardiovascular autonomic function. This study sought to investigate cardiovascular autonomic function in patients with ischemic stroke with carotid stenosis. METHODS: Eighty-five patients with ischemic stroke (58 ones without carotid stenosis and 27 ones with carotid stenosis, average 6 months after stroke onset) and 37 elderly controls were recruited. All performed Ewing's battery autonomic function tests. RESULTS: From Ewing's battery of autonomic function tests, atypical, definite, or severe autonomic dysfunction was identified in 69.0% patients without carotid stenosis and 88.9% with carotid stenosis, with significant difference between the two groups, and the prevalence of autonomic dysfunction in both groups was higher than that in controls (21.6%). Patients with carotid stenosis showed impairment of all parasympathetic tests (all P < 0.05) and one of the sympathetic tests [Mean fall in systolic blood pressure (BP) on standing: P = 0.051], and those without carotid stenosis only showed impairment in two parasympathetic tests (Valsalva ratio: P = 0.014; heart rate response to deep breathing: P < 0.001) in comparison with controls. Patients with carotid stenosis had significantly more impairment than those without carotid stenosis in some autonomic parameters (Valsalva ratio: P < 0.05; mean fall in systolic BP on standing: P < 0.05). CONCLUSIONS: Cardiovascular autonomic function is impaired in patients with ischemic stroke, but patients with carotid stenosis show more severely impaired parasympathetic and sympathetic functions. PMID- 22077727 TI - Neuropsychological evaluation and follow-up of children with cerebellar cortical dysplasia. AB - AIM: To describe neuropsychological disturbances and the developmental course associated with cerebellar cortical dysplasia (CCD). METHOD: The neuroimaging findings from 10 children (five males, five females; aged 3-10 y) with CCD were reviewed and classified. These children all underwent clinical neurological examination and neuropsychological assessment (NPA) on admission, then were followed for an average of 6 years using the cognitive Wechsler Scale, Vineland Adaptive Behavior Scales, and Rey-Osterrieth Complex Figure/McCarthy Drawing subtests. RESULTS: Based on magnetic resonance imaging, CCD was categorized as minor (n = 4), moderate (n = 1), and severe (n = 5). The first NPA disclosed mental retardation* in six (profound, three; moderate, one; mild, two) and normal intelligence in four (low, two; average, one; high, one), but with verbal/performance dissociation in three cases. Socio-adaptive functions were altered in all children except one. Visuospatial abilities were delayed in eight children. In the follow-up, no progression was observed in the three cases with profound mental retardation, whereas the remainder showed homogeneous or disharmonic progression, including improvement or deterioration of verbal/performance function. Cognitive impairment and evolution was not associated with the degree of cerebellar involvement. INTERPRETATION: The neuropsychological profile and evolution associated with CCD do not appear to be predictable, and some features might improve over time. PMID- 22077728 TI - Dental erosion and salivary flow rate in cerebral palsy individuals with gastroesophageal reflux. AB - BACKGROUND: A high prevalence of gastroesophageal reflux (GERD) has been observed in individuals with cerebral palsy (CP). One of the main risks for dental erosion is GERD. This study aimed to evaluate the presence of GERD, variables related to dental erosion and associated with GERD (diet consumption, gastrointestinal symptoms, bruxism), and salivary flow rate, in a group of 46 non institutionalized CP individuals aged from 3 to 13 years. METHODS: Twenty CP individuals with gastroesophageal reflux (GERDG) and 26 without gastroesophageal reflux (CG) were examined according to dental erosion criteria, drinking habits, presence of bruxism, and salivary flow rate. A face-to-face detailed questionnaire with the consumption and frequency of acid drinks, gastrointestinal symptoms (regurgitation and heart burn), and the presence of bruxism were answered by the caregivers of both groups. Unstimulated whole saliva was collected under slight suction, and salivary flow rate (ml/min) was calculated. RESULTS: The GERDG presented higher percentages of younger quadriplegics individuals compared to CG. The presence of regurgitation, heart burn, and tooth erosion (Grade 1) was significantly more prevalent in GERDG. It was observed difference in the salivary flow rate between the studied groups. On logistic multivariate regression analysis, the unique variable independently associated with the presence of GERD was dental erosion (P = 0.012, OR 86.64). CONCLUSION: The presence of GERD contributes significantly to dental erosion in the most compromised individuals with quadriplegics cerebral palsy individuals, increasing the risk of oral disease in this population. PMID- 22077729 TI - General application of the National Institute for Health and Clinical Excellence (NICE) guidance for active surveillance for men with prostate cancer is not appropriate in unscreened populations. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance (AS) is a well recognised management strategy to minimise the morbidity associated with radical treatment of prostate cancer. The National Institute for Health and Clinical Excellence guidelines initially suggested that all men with low-risk prostate cancer should first be offered AS. The cohort of men with upstaging and upgrading of prostate cancer from diagnosis to final pathology has been described in North American and European populations. As the rate of PSA testing in Britain is lower than North America and parts of Europe, the risk of more advanced disease at diagnosis of prostate cancer is higher. The present study is one of the first to examine this cohort in a British population and found the rate of features of advanced disease (extracapsular extension, seminal vesicle involvement and Gleason 4 + 3, or 8-10) to be 37.2%. OBJECTIVE: To determine if the National Institute for Health and Clinical Excellence (NICE) guidelines for men with low risk prostate cancer were generally applicable in unscreened populations. PATIENTS AND METHODS: Retrospective analysis of prospectively collected case series from a single tertiary care centre in England. In all, 700 consecutive men treated for prostate cancer from 2005 by robot-assisted laparoscopic prostatectomy (RALP) were included. Patients satisfying NICE criteria for low risk disease (PSA level < 10 ng/mL and Gleason score <= 6 and cT1-2a) had their pathological samples analysed for advanced disease, defined as extracapsular extension (ECE: pT3), seminal vesicle involvement (SVI), Gleason sum 7, or 8-10 or node-positive disease. RESULTS: In all, 275 patients (39.2%) met the NICE low risk criteria, but pathologically advanced disease was found in 37.2% of this group. There was ECE in 71 patients (25.8%), 10 had SVI (3.6%), nine (3.3%) had Gleason score 7(4 + 3), and 12 had Gleason sum 8-10 (4.4%). CONCLUSIONS: The NICE guidance was developed largely on data from North America where populations are highly screened using PSA testing. In the UK, many men with low-risk disease features have high-risk disease and the general applicability of the NICE guidance is questionable in unscreened populations. We recommend that radical therapy is discussed as an alternative option to active surveillance. PMID- 22077730 TI - Knowledge about patients' rights among professionals in public health care in Finland. AB - BACKGROUND: The legal rights of patients include civil rights for patients and the duties of healthcare professionals. Knowledge of legislation and the ability to put juridical norms into practice are among the main aspects of professionals. AIM: The aim of the study was to describe the level of healthcare professionals' knowledge about patients' legal rights and to describe background variables associated with the knowledge. The legal rights are based on the Finnish Act on the Status and Rights of Patients. METHOD: The data were collected from healthcare professionals (nurses and physicians) in public health care in Finland (recruited N = 290, responded n = 191) with a questionnaire designed for the study. The response rate was 66%. The data were analysed statistically. RESULTS: Healthcare professionals were partially familiar with patients' legal rights. The right to good health care, treatment and access to care and right to self determination were the best-known areas. The respondents lacked knowledge on the right to information and the right to use the services of patient ombudsman. Based on self-evaluation, half of the respondents thought that they had weak knowledge of the legislation on patients' rights. However, they perceived knowledge about patients' rights as being important. There was no correlation between respondents' self-evaluated knowledge and actual scoring on the knowledge test. CONCLUSION: These results implicate a need for further education aimed at healthcare professionals and development of professional training about patients' legal rights. PMID- 22077731 TI - A primer for biomedical scientists on how to execute model II linear regression analysis. AB - 1. There are two very different ways of executing linear regression analysis. One is Model I, when the x-values are fixed by the experimenter. The other is Model II, in which the x-values are free to vary and are subject to error. 2. I have received numerous complaints from biomedical scientists that they have great difficulty in executing Model II linear regression analysis. This may explain the results of a Google Scholar search, which showed that the authors of articles in journals of physiology, pharmacology and biochemistry rarely use Model II regression analysis. 3. I repeat my previous arguments in favour of using least products linear regression analysis for Model II regressions. I review three methods for executing ordinary least products (OLP) and weighted least products (WLP) regression analysis: (i) scientific calculator and/or computer spreadsheet; (ii) specific purpose computer programs; and (iii) general purpose computer programs. 4. Using a scientific calculator and/or computer spreadsheet, it is easy to obtain correct values for OLP slope and intercept, but the corresponding 95% confidence intervals (CI) are inaccurate. 5. Using specific purpose computer programs, the freeware computer program smatr gives the correct OLP regression coefficients and obtains 95% CI by bootstrapping. In addition, smatr can be used to compare the slopes of OLP lines. 6. When using general purpose computer programs, I recommend the commercial programs systat and Statistica for those who regularly undertake linear regression analysis and I give step-by-step instructions in the Supplementary Information as to how to use loss functions. PMID- 22077732 TI - Population policies in socialist countries of Europe. AB - Abstract The emergence, in the mid-sixties, of policies aimed at counteracting rapid fertility decline in some socialist countries of Europe is discussed in the paper. Following a summary of recent population trends and policies in nine European socialist countries, and brief comments on ideological and theoretical considerations, factors relevant to policy decision are discussed. Population policies aiming at encouraging fertility exist in five countries, viz. German Demographic Republic, Romania, Bulgaria, Hungary and Czechoslovakia. Recent developments appear to include attempts to stimulate third births with measures aiming to improve economic conditions of large families, the status of women, education and restriction of induced abortion. PMID- 22077733 TI - Vital rates in India 1961-71 estimated from 1971 census data. AB - Abstract In the last decade the increase in the population of India, while, of course, very large, was smaller than predicted by official forecasts. With the use of recent census and sample registration data - in the absence of age specific rates and adequate vital statistics - this paper provides estimates of fertility and mortality through the reverse-survival and forward-projection methods. Birth rates are estimated as 40.5-42, death rates as 18-20, and life expectancy at birth as 45-46 years. Mortality decline had been smaller than forecast but more than during any comparable period in the past, even though current mortality levels, particularly infant mortality, are still high. Males continue to have a longer life expectation than females, with a difference that has widened in the past decade. The decline of between seven and ten per cent in the crude birth rate is largely due to changes in marital fertility and to some extent to changes in age and marital composition. Because of greater decline in death rates than birth rates, the 1961-71 decade shows a higher rate of population growth than previous periods. PMID- 22077734 TI - Regional trends in fertility and mortality in Brazil. AB - Abstract Questions asked in the 1970 Brazilian census allow the application of fertility and childhood mortality techniques developed by W. Brass. Using some propositions based on fertility estimates from the 1970 census data it was possible to extend the analysis to the 1940, 1950 and 1960 censuses. Estimates are also provided for ten Brazilian regions, for 1940, 1950 and 1970. These estimates show a slight decrease in the fertility level for the country as a whole, but two different trends at regional levels. Between 1940-50 and 1960-70 the poorer regions experienced constant or increasing fertility levels while developed regions experienced declining ones, with only one exception. The mortality estimates indicate a consistent decline in the mortality level of all regions, but also a divergent trend between poor and developed regions, in life expectancies at birth. This work is a summarized version of Chapters II, III and IV of my Ph.D. thesis written under the supervision of Professor D. V. Glass and Mr J. Hobcraft at the University of London. I am most grateful to my supervisors as well as to Professor W. Brass for valuable comments on several aspects of the thesis. While carrying out this study, the author was supported by grants from the Federal University of Minas Gerais, Brazil, and the Ford Foundation. PMID- 22077735 TI - Demographic aspects of fertility in Thailand. AB - Abstract Data from a national rural and urban sample survey are analysed in order to examine various demographic aspects of fertility in Thailand. Marital fertility rates found for Thailand are among the highest in Asia. Particularly noteworthy is the persistence of high fertility at older ages of childbearing for rural women. Cumulative fertility shows a pronounced relationship with age at marriage and current marital status. Women who marry at an older age or who experience disruption of their marriages are clearly more likely to have fewer children ever born. Differences in both current and cumulative fertility are strongly associated with residence. Rural women who constitute the vast majority of Thai women, experience the highest fertility, Bangkok-Thonburi women experience the lowest fertility and provincial urban women are characterized by an intermediate fertility level which is closer, however, to the experience of their counterparts in the capital than in the countryside. Rural-urban fertility differences are mitigated but by no means eliminated by differences in infant mortality. In both rural and urban areas a positive association between cumulative fertility and infant morality is evident. Breast-feeding, commonly practised for extended periods-among both rural and urban Thai women, undoubtedly serves to some extent as an intervening variable in this relationship. A comparison of current fertility with cumulative fertility strongly suggests that a decline in marital fertility has been under way recently among urban women, especially those residing in the capital, but not at all among rural women. Although it seems safe to assume that the urban fertility decline results in large part from an increasing use of contraception among urban women, those still in the reproductive ages who were using or had previously used birth control were characterized by higher cumulative fertility than women who had never practised contraception. Evidently couples resort to family planning only late in the family building process after they have already achieved or exceeded the number of children they wish to have. PMID- 22077736 TI - Fertility and number of partnerships in Barbados. AB - Abstract This paper examines the relationship between the number of partnerships ever engaged in and fertility, as measured by the average number of live births. It was found that the larger the number of partnerships in which a woman had been engaged the higher is her fertility. This relationship between partnerships and fertility remains even when such variables as present age, age at first partnership, age at first pregnancy, time lost between unions, time spent in partnerships, time since entry into the first partnership, type of sexual union at first pregnancy, present type of sexual union, and current use or non-use of contraceptives are controlled by cross tabulation. Correlation analysis also bears out the positive relationship between partnerships and fertility. The data for this study came from a sample survey of 4,199 women of lower, and lower middle, socio-economic status who were interviewed in 1971 on the island of Barbados. The authors have confidence in the reliability and validity of their data and hence in their findings and conclusions. The authors believe that their findings contradict the previously established positive relationship between patterns of stability of sexual unions and fertility in English-speaking Caribbean societies. They conclude that the relationship was either not rigorously examined in the past or else has undergone changes as these societies modernize economically and socially. PMID- 22077737 TI - The effect of an additional birth on low-income urban families. AB - Abstract The effects of the birth of an additional child to families living in poverty areas of New York City are studied in this paper. Surveys conducted by the National Opinion Research Center in 1965 and 1967 provided the data in a panel of parous or married women of childbearing age. Control ling for the number of children in the family in 1965, the non-occurrence of an additional birth in the following two years was found to have a significant effect on current income, savings, reliance on public assistance, general ability to plan and organize one's household, and wife's employment. No significant effects were found with respect to possession of consumer durables or attending a school or training course. While many claims have been made about the beneficial effects of family planning on family welfare, this study is among a very small number where such effects are empirically documented. PMID- 22077738 TI - Systematic and chance components in fertility measurement. AB - Abstract A Monte Carlo simulation model of fertility is developed to incorporate a decline in fecundability with age of women as well as a variation between women, and a family planning strategy in which couples prefer certain sizes of families and seek to lengthen the last planned birth interval. In the simulation of family planning and non-family planning populations, segmental parity tables are computed. These are tables in which the numbers of women in the columns representing the completed family sizes are sub-divided by rows representing the sizes of the families for shorter durations of marriage. The couples' success in their plans, under various conditions, and the rapidity with which family sizes stabilize, are among the results obtained from the simulation. The application of the tables to the estimation of family size preferences from observed family size distributions is also discussed. PMID- 22077739 TI - Risk, uncertainty and family formation: The social context of poverty groups. AB - Abstract Despite the assumptions of many demographers that the net returns from children for non-elite groups in underdeveloped areas are likely to be negative, high fertility persists in most of these societies. Both cultural and institutional explanations have been proposed to account for this. We attempt to provide some mediation between these competing models, by introducing the elements of risk and uncertainty as factors likely to induce poverty and lead works to opt for the 'high fertility, low quality' pattern of investment of time and money in family formation. Drawing upon the work of Wharton in subsistence agriculture practices, several alternative decision-making models are proposed to account for both the persistence of high fertility, and the declines that have been registered in selected areas, such as Taiwan and perhaps China. The empirical work of Mueller on Taiwanese expectations of returns on children and the concomitant variation in family-size preferences is consistent with the models proposed. Some implications for uncertainty and risk-reduction strategies in family planning and other social welfare programmes are drawn. PMID- 22077742 TI - Effect of communication style and physician-family relationships on satisfaction with pediatric chronic disease care. AB - Over 8% of children have a chronic disease and many are unable to adhere to treatment. Satisfaction with chronic disease care can impact adherence. We examine how visit satisfaction is associated with physician communication style and ongoing physician-family relationships. We collected surveys and visit videos for 75 children ages 9-16 years visiting for asthma, diabetes, or sickle cell disease management. Raters assessed physician communication style (friendliness, interest, responsiveness, and dominance) from visit videos. Quality of the ongoing relationship was measured with four survey items (parent-physician relationship, child-physician relationship, comfort asking questions, and trust in the physician), while a single item assessed satisfaction. Correlations and chi square were used to assess association of satisfaction with communication style or quality of the ongoing relationship. Satisfaction was positively associated with physician to parent (p < 0.05) friendliness. Satisfaction was also associated with the quality of the ongoing parent-physician (p < 0.001) and child-physician relationships (p < 0.05), comfort asking questions (p < 0.001), and trust (p < 0.01). This shows that both the communication style and the quality of the ongoing relationship contribute to pediatric chronic disease visit satisfaction. PMID- 22077743 TI - A genome-wide phylogenetic reconstruction of family 1 UDP-glycosyltransferases revealed the expansion of the family during the adaptation of plants to life on land. AB - For almost a decade, our knowledge on the organisation of the family 1 UDP glycosyltransferases (UGTs) has been limited to the model plant A. thaliana. The availability of other plant genomes represents an opportunity to obtain a broader view of the family in terms of evolution and organisation. Family 1 UGTs are known to glycosylate several classes of plant secondary metabolites. A phylogeny reconstruction study was performed to get an insight into the evolution of this multigene family during the adaptation of plants to life on land. The organisation of the UGTs in the different organisms was also investigated. More than 1500 putative UGTs were identified in 12 fully sequenced and assembled plant genomes based on the highly conserved PSPG motif. Analyses by maximum likelihood (ML) method were performed to reconstruct the phylogenetic relationships existing between the sequences. The results of this study clearly show that the UGT family expanded during the transition from algae to vascular plants and that in higher plants the clustering of UGTs into phylogenetic groups appears to be conserved, although gene loss and gene gain events seem to have occurred in certain lineages. Interestingly, two new phylogenetic groups, named O and P, that are not present in A. thaliana were discovered. PMID- 22077744 TI - Editorial: Preventing suicide by using consumer peer specialists. PMID- 22077745 TI - Managing risk: clinical decision-making in mental health services. AB - Risk assessment and management is a major component of contemporary mental health practice. Risk assessment in health care exists within contemporary perspectives of management and risk aversive practices in health care. This has led to much discussion about the best approach to assessing possible risks posed by people with mental health problems. In addition, researchers and commentators have expressed concern that clinical practice is being dominated by managerial models of risk management at the expense of meeting the patient's health and social care needs. The purpose of the present study is to investigate the risk assessment practices of a multidisciplinary mental health service. Findings indicate that mental health professionals draw on both managerial and therapeutic approaches to risk management, integrating these approaches into their clinical practice. Rather than being dominated by managerial concerns regarding risk, the participants demonstrate professional autonomy and concern for the needs of their clients. PMID- 22077746 TI - Obstetric and neonatology nurses' attitudes, beliefs, and practices related to the management of symptoms of maternal depression. AB - Although maternal depression is a common emotional disorder, assessment and intervention rates are low. Using a cross-sectional survey design, we examined attitudes, beliefs, and practices of obstetrical and neonatology nurses toward the management of symptoms of maternal depression (SMD). Nurses believed they were responsible to assess for SMD and intervene with women showing SMD. However, only 50% assessed for SMD at least once monthly. Identified barriers to care were: lack of time, training, language, and patient and family beliefs. NICU nurses reported lower confidence, knowledge, and skills, than other nurses who participated in this study. This study shows there is a need to enhance nurses? confidence in assessing and intervening with SMD, and to clarify the referral process. PMID- 22077747 TI - Becoming a psychiatric/mental health nurse in the UK: a qualitative study exploring processes of identity formation. AB - Identity studies are well established across the social science literature with mental health nursing beginning to offer evidenced insights into what may, or may not, constitute key identity performances. For mental health nursing these performances remain contested, both from within the profession and from international contexts that favour generic constructions of mental health. This paper offers findings from a qualitative study that focused upon the process of how mental health nursing identity development is influenced, rather than what that identity may or may not be. These findings highlight that mental health nurses (MHNs) not only form their identity around service user centred education and training, but that many also use the education as a means to leave the profession. Through highlighting the impact of informal education (i.e., through work), formal education, and training upon the formation of mental health nursing identity, nurses are potentially alerted to the importance of clinically focussed mental health being prominent within curricula, rewarding mental health nursing skills specialisation, and the importance of the role of the service user in mental health nurse education and, hence, identity formation. PMID- 22077749 TI - A psychometric analysis of the functional social support questionnaire in low income pregnant women. AB - The purpose of this study was to examine the psychometric properties of the Functional Social Support Questionnaire (FSSQ) in pregnant women. A secondary analysis of data from 186 low-income pregnant women in their third trimester was conducted to assess the internal consistency reliability, dimensionality, and concurrent validity of the FSSQ. Cronbach's alpha was .83. Factor analysis supported the unidimensionality of the FSSQ. Correlations with the Interpersonal Support Evaluation List (ISEL) and the Center for Epidemiologic Studies Depression Scale (CES-D) supported concurrent and construct validity. This secondary analysis provided evidence of the psychometric soundness of the FSSQ in this sample. PMID- 22077748 TI - Depressive symptoms in extended-care employees: children, social support, and work-family conditions. AB - To examine the relation between having a child aged 18 years and under in the home and employee depressive symptoms, we analyzed cross-sectional data from four extended care facilities in Boston, MA (n = 376 employees). Results show that having a child is associated with slightly higher depressive symptoms. The strength of this relationship in our models is attenuated with the inclusion of social support at home (beta = 1.08 and beta = 0.85, with and without support, respectively) and may differ by gender. We recommend that future research examine the role of parenting and social support in predicting employee mental health. PMID- 22077750 TI - Knowledge and attitudes of Jordanian nurses towards patients with HIV/AIDS: findings from a nationwide survey. AB - This study explored the knowledge and attitudes of Jordanian nurses toward patients with HIV/AIDS, particularly in regards to their sources of information and education. This survey utilized a cross-sectional design. A self-administered questionnaire developed by Eckstein was used in collecting the data. A total of 922 nurses completed the questionnaire. Overall, Jordanian nurses expressed negative attitudes toward patients with HIV/AIDS, and their level of HIV/AIDS knowledge was weak. Weak knowledge level was recorded among nurses in the following subsections: agent and immunology; course and manifestation; transmission and incidence; and precaution and prevention. Only in one subsection (risk group), did nurses show a good level of knowledge about HIV/AIDS. More than two-thirds of nurses (84%) refused to provide care to patients who tested positive for HIV/AIDS. Most of the nurse participants believed that currently provided HIV/AIDS information resources were inadequate (81.4 %). The majority of nurses were interested in support groups for staff nurses (96.5%). The major source of HIV/AIDS information obtained by Jordanian nurses was through Internet web sites (52.7%). The majority of nurses (96.2%) ranked their fear of getting AIDS from their nursing practice as overwhelming. The total attitude of participants towards patients with HIV/AIDS in all five subsections (i.e., fear of contagion, social stigma, fatal outcome of the disease, direct care, and education and counseling) was negative (84.3%). Accurate knowledge about HIV/AIDS along with an in-depth understanding of patients? needs can help alleviate much of the fear, anxiety, and stigma associated with caring for patients with HIV/AIDS. PMID- 22077751 TI - Examining the efficacy of no-suicide contracts in inpatient psychiatric settings: implications for psychiatric nursing. AB - Verbal and written no-suicide contracts are commonly practiced by psychiatric nurses in inpatient psychiatric facilities. However, evidence is sparse regarding whether no-suicide contracts are effective tools for maintaining patient safety. The purpose of this paper is to examine the use of the verbal and written no suicide contracts, discuss the resulting implications for psychiatric nurses on inpatient units, and suggest alternative clinical practices for inpatient psychiatric nurses to utilize to increase patient safety. PMID- 22077752 TI - Heartbreak and physical pain linked in brain. PMID- 22077756 TI - Cerebellar haemorrhage in the extremely preterm infant. AB - AIM: The aim of this study was to investigate the incidence, risk factors and developmental outcomes of cerebellar haemorrhage in the extremely preterm infant. METHODS: Over a 4-year period from January 2004, all patients with cerebellar haemorrhage born at 24-27 weeks gestation or with a birthweight < 1000 g were identified from database review. All patients had cranial ultrasound scans including views from the mastoid fontanelle. To verify the incidence, a review of all reports over the 4-year period and a review of all cranial imaging over a 2 year period were carried out. RESULTS: From the data analysed on 339 neonates, five cases of cerebellar haemorrhage were identified, four on ultrasound scan (1.2%) and one on magnetic resonance imaging (1.5% total). Two cases were associated with grade III peri-intraventricular haemorrhage. The cases had diverse maternal, antenatal and post-natal risk factors. The two with associated peri-intraventricular haemorrhage have developmental delay. The cases with isolated cerebellar haemorrhage had good neurodevelopmental outcomes. CONCLUSIONS: A low incidence of cerebellar haemorrhage identified from the mastoid fontanelle was demonstrated. The neurodevelopmental outcome was better than that described in previous reports. PMID- 22077757 TI - Surface plasmon-enhanced nanopillar photodetectors. AB - We demonstrate nanopillar-(NP) based plasmon-enhanced photodetectors (NP-PEPDs) operating in the near-infrared spectral regime. A novel fabrication technique produces subwavelength elongated nanoholes in a metal surface self-aligned to patterned NP arrays that acts as a 2D plasmonic crystal. Surface plasmon Polariton Bloch waves (SPP-BWs) are excited by the metal nanohole array resulting in electric field intensity "hot spots" in the NP. The NP periodicity determines the peak responsivity wavelength while the nanohole asymmetry produces polarization-dependent coupling of the SPP-BW modes. Resulting photodetectors have 0.28 A/W responsivity peaked at 1100 nm at a reverse bias of -5 V. Designs for further increasing the optical coupling efficiency into the nanopillar are explored. This technology has potential applications for plasmonically enhanced focal plane arrays and plasmonic photovoltaics. PMID- 22077759 TI - The effect of facial expression and gaze direction on memory for unfamiliar faces. AB - We report data from an experiment that investigated the influence of gaze direction and facial expression on face memory. Participants were shown a set of unfamiliar faces with either happy or angry facial expressions, which were either gazing straight ahead or had their gaze averted to one side. Memory for faces that were initially shown with angry expressions was found to be poorer when these faces had averted as opposed to direct gaze, whereas memory for individuals shown with happy faces was unaffected by gaze direction. We suggest that memory for another individual's face partly depends on an evaluation of the behavioural intention of that individual. PMID- 22077758 TI - Effect of saliva viscosity on the co-aggregation between oral streptococci and Actinomyces naeslundii. AB - BACKGROUND: The co-aggregation of oral bacteria leads to their clearance from the oral cavity. Poor oral hygiene and high saliva viscosity are common amongst the elderly; thus, they frequently suffer from pneumonia caused by the aspiration of oral microorganisms. OBJECTIVES: To examine the direct effect of saliva viscosity on the co-aggregation of oral streptococci with actinomyces. MATERIALS AND METHODS: Fifteen oral streptococcal and a single actinomyces strain were used. Co aggregation was assessed by a visual assay in phosphate buffer and a spectrophotometric assay in the same buffer containing 0-60% glycerol or whole saliva. RESULTS: Nine oral streptococci co-aggregated with Actinomyces naeslundii ATCC12104 in the visual assay and were subsequently used for the spectrophotometric analysis. All tested strains displayed a decrease in co aggregation with increasing amounts of glycerol in the buffer. The co-aggregation of Streptococcus oralis with A. naeslundii recovered to baseline level following the removal of glycerol. The per cent co-aggregation of S. oralis with A. naeslundii was significantly correlated with the viscosity in unstimulated and stimulated whole saliva samples (correlation coefficients: -0.52 and -0.48, respectively). CONCLUSION: This study suggests that saliva viscosity affects the co-aggregation of oral streptococci with actinomyces and that bacterial co aggregation decreases with increasing saliva viscosity. PMID- 22077760 TI - An overview of swine influenza. AB - Summary Swine influenza is a highly infectious viral disease of pigs, causing considerable economic impact. The causative agent is known as a type A orthomyxovirus with a segmented RNA genome. Influenza type A virus is a highly contagious pathogen among a limited number of birds and mammals. The objective of this review is to summarize the current knowledge in swine influenza infection in pigs with emphasizing on epidemiology, pathogenesis, diagnostic techniques and control measures. PMID- 22077761 TI - First chronic wasting disease (CWD) surveillance of roe deer (Capreolus capreolus) in the Northern part of Belgium. AB - Summary Cases of chronic wasting disease (CWD) in wild cervids have yet not been reported in Europe, Whereas the disease is considered enzootic in free ranging mule deer, Rocky mountain elk and White-tailed deer in the area of Colorado, Wyoming, and Nebraska. New foci of CWD continue to be detected in other parts of the United States. However, no large-scale active epidemiosurveillance of European wild cervids is yet installed in Europe. In accordance with the opinion of the European Scientific Steering Conunittee, a preliminary (active) surveillance scheme was installed, in order to Improve the knowledge of the CWD status of wild cervids (roe deer) in the Northern part of Belgium. Spleen samples (n = 206) and brain samples (n = 222) of roe deer collected in the Northern part of Belgium, were examined for CWD using the antigen-capture enzyme-linked immunoassay (EIA) of IDEXX. Afterwards, the EIA was systematically confirmed by immunohistochemistry using three antibodies, namely R524, 2G11 and 12F10. There were no indications on the occurrence of TSE in any of the samples. A Bayesian framework was used for the estimation of the true prevalence of CWD in the Northern part of Belgium that was estimated to have a median value of zero with a 95(th) percentile value of 0.0049 and 0.0045 for spleen and brain samples respectively. PMID- 22077762 TI - Borna Disease Virus (BDV) infection in cats a concise review based on current knowledge. AB - Summary Persistent viral infections of the central nervous system have been the subject of intense interest for decades. One of these viral agents has been identified as Borna disease virus (BDV) of the family Bornaviridae. There have been various reports that link BDV to staggering disease in cats, with symptoms that include ataxia and behavioural disorders, and the disease is often referred to as feline Borna disease. Serological and molecular detection of BDV has been reported at a higher prevalence in cats with neurological disorders in comparison to healthy cats. The transmission route(s) of BDV remain largely unknown, and the hypothesis that BDV is a zoonotic agent is yet to be proven. This review summarises the current knowledge on BDV infection in cats and discusses epidemiological aspects of infection. PMID- 22077763 TI - Reviews on animal diseases recently published in other journals. PMID- 22077765 TI - Protein-protein binding sites prediction by 3D structural similarities. AB - Identifying the location of binding sites on proteins is of fundamental importance for a wide range of applications including molecular docking, de novo drug design, structure identification, and comparison of functional sites. In this paper, we develop an efficient approach for finding binding sites between proteins. Our approach consists of four steps: local sequence alignment, protein surface detection, 3D structure comparison, and candidate binding site selection. A comparison of our method with the LSA algorithm shows that the binding sites predicted by our method are somewhat closer to the actual binding sites in the protein-protein complexes. The software package is available at http://sites.google.com/site/guofeics/pro-bs for noncommercial use. PMID- 22077766 TI - Resolution and quantification of complex mixtures of polycyclic aromatic hydrocarbons in heavy fuel oil sample by means of GC * GC-TOFMS combined to multivariate curve resolution. AB - Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC * GC-TOFMS) combined to multivariate curve resolution-alternating least squares (MCR-ALS) is proposed for the resolution and quantification of very complex mixtures of compounds such as polycyclic aromatic hydrocarbons (PAHs) in heavy fuel oil (HFO). Different GC * GC-TOFMS data slices acquired during the analysis of HFO samples and PAH standards were simultaneously analyzed using the MCR-ALS method to resolve the pure component elution profiles in the two chromatographic dimensions as well as their pure mass spectra. Outstandingly, retention time shifts within and between GC * GC runs were not affecting the results obtained using the proposed strategy and proper resolution of strongly coeluted compounds, baseline and background contributions was achieved. Calibration curves built up with standard samples of PAHs allowed the quantification of ten of them in HFO aromatic fractions. Relative errors in their estimated concentrations were in all cases below 6%. The obtained results were compared to those obtained by commercial software provided with GC * GC-TOFMS instruments and to Parallel Factor Analysis (PARAFAC). Inspection of these results showed improvement in terms of data fitting, elution process description, concentration relative errors and relative standard deviations. PMID- 22077767 TI - Cerebellar contribution to cognitive, emotional, and behavioural functions in children with cerebellar abnormalities. PMID- 22077768 TI - Gabapentin enacarbil for the treatment of restless legs syndrome (RLS). AB - INTRODUCTION: Gabapentin enacarbil is a new treatment for restless legs syndrome (RLS). It is a prodrug of the anticonvulsant gabapentin. However, unlike gabapentin, gabapentin enacarbil does not demonstrate saturable absorption. This allows for once-daily dosing and less variability in serum levels. AREAS COVERED: This review focuses on therapies used to treat RLS, both historical and recent. Data from available trials are summarized, with a particular focus on the efficacy and safety of gabapentin enacarbil. Potential advantages and disadvantages of this therapy in comparison with other RLS treatment modalities are discussed. EXPERT OPINION: Placebo-controlled trials of gabapentin enacarbil demonstrate considerable efficacy in the treatment of RLS. However, head-to-head trials comparing gabapentin enacarbil with other medications used in the treatment of RLS, including gabapentin, are lacking. Potential advantages with gabapentin enacarbil related to its pharmacokinetic profile are thus difficult to ascertain. Efficacy of gabapentin enacarbil appears comparable with that of the dopamine agonists, long considered the therapy of choice in patients with RLS. Given the lack of direct-comparison trials, and the significant cost differential of gabapentin enacarbil versus established therapies, the drug is likely to be used for patients who have failed other medication trials, or those who experience prolonged symptoms and prefer once-daily dosing. PMID- 22077769 TI - Pyrophthalones as blue wavelength absorbers in thermoplastic media. AB - We have explored the utility of pyrophthalones as violet-blue light filtering dyes in polymer matrices for wavelengths below 450 nm. Further, we have investigated the photodegradation of these molecules in thermoplastic media and the mechanisms behind their degradation. Finally, a range of additives have been explored to improve the photostability of these molecules to achieve the desired performance. PMID- 22077770 TI - Formal synthesis of berkelic acid: a lesson in alpha-alkylation chemistry. AB - The full details of our enantioselective formal synthesis of the biologically active natural product berkelic acid are described. The insertion of the C-18 methyl group proved challenging, with three different approaches investigated to install the correct stereochemistry. Our initial Horner-Wadsworth-Emmons/oxa Michael approach to the berkelic acid core proved unsuccessful upon translation to the natural product itself. However, addition of a silyl enol ether to an oxonium ion, followed by a one-pot debenzylation/spiroketalisation/thermodynamic equilibration procedure, afforded the tetracyclic structure of the berkelic acid core as a single diastereoisomer. PMID- 22077771 TI - Vagal nerve modulation: a promising new therapeutic approach for cardiovascular diseases. AB - The physiological activities of the mammalian heart are regulated by the autonomic nervous system. An imbalanced autonomic nervous system with increased sympathetic tone and reduced vagal tone has been implicated in cardiovascular diseases. Experimental and clinical reports have demonstrated that vagal nerve activation is able to improve outcomes for multiple cardiovascular diseases, such as ischaemic heart disease, heart failure, arrhythmia and hypertension. In this paper, we mainly focus on the potential cardioprotective mechanisms of vagal nerve activation. Based on the knowledge gained from our experiments and other published reports, vagal activation results in cardioprotection is not only associated with heart rate, anti-adrenergic effect but also related to anti inflammatory activity, regulation of cellular redox states and regulation of mitochondrial targets. In conclusion, vagal nerve activation may be a promising new therapeutic approach for the treatment of cardiovascular diseases. PMID- 22077772 TI - Risks with older adults in acute care settings: UK occupational therapists' and physiotherapists' perceptions of risks associated with discharge and professional practice. AB - Internationally, there is evidence that hospital discharge to home for older adults is a complex and challenging process that is dependent upon multidisciplinary team working. At the centre of the discharge process is the management of risk, which involves occupational therapists and other healthcare professionals managing perceived dangers and determining why some dangers are seen as presenting risks while others are not. This study did not aim to explore interprofessional differences but to ascertain a greater understanding of professionals' perceptions of risk in acute care settings. This qualitative study utilised 12 semi-structured interviews with seven occupational therapists and five physiotherapists in the United Kingdom (UK). During the interview, therapists were asked to read and answer questions on a validated vignette. The interview data were subjected to thematic content analysis and the vignettes to template analysis. Our research is one of the first studies to explore therapists' perceptions of risk with older adults in acute care settings. Our study has highlighted that perception of risk does have an impact on discharge decision-making and location. Therapists used negative terminology to refer to patients who wanted to take risks, which could be a reflection of the therapists' anxiety. Mental capacity, and patients' functioning and safety were key factors in risk decision-making with older adults. Our research has highlighted the potential value of multidisciplinary working to manage risk situations and the need for reflection and discussion regarding how persons who do not have capacity wishes are managed within acute care settings. There is a need to develop an interprofessional care pathway to guide clinicians through the risk decision making process which needs to ensure that the client's opinions and wishes are taken into account throughout. PMID- 22077773 TI - Recent fertility in Mexico: measurement and interpretation. AB - Summary Mexican fertility has remained at a high level (a crude birth rate of 42-46) in spite of rapid economic development and its concomitants: rising levels of urbanization, education, income, and female labour force participation, and falling levels of infant mortality and agricultural population, combined with rural-urban migration. Data on child-woman ratios and children-ever-born statistics, for Mexico and each state, suggest that the constant crude birth rate is not masking age or region-specific declines in fertility. Cross-section regressions are employed in an attempt to explain Mexico's paradoxical fertility behaviour. Using measures of income, education, urbanization, occupational status, industrial composition, labour force participation, and the sex ratio, in a weighted log-linear form, a large portion of the variation in state adjusted child-woman ratios is explained by the 'demographic transition' variables. The only two which might possibly explain the trend in Mexican fertility are the income variable and the sex ratio, which have positive influences on Mexican fertility in 1960 and 1970. PMID- 22077774 TI - The fertility of the asian community of East Africa. AB - Summary Fertility indices of one sort or another can be calculated for the Asian populations of Uganda and Kenya back to 1931. These indices suggest that fertility has fallen sharply during the 1950s and 1960s. Considerable problems are experienced in trying to determine the actual level of fertility, however, since all the techniques developed to deal with defective data are so affected by the falling fertility and migratory movements of the population, as to be virtually useless. An analysis of the causes of the fertility decline suggests that both changes in marriage patterns and changes in fertility within marriage have contributed to the fall, and that these changes have come about as a result of the better education and economic opportunities available to the Asian community. PMID- 22077775 TI - Children as by-products, investment goods and consumer goods: A Review of some micro-economic models of fertility. AB - Summary This paper is a review of a number of applications of traditional micro economics to the analysis of fertility. In this paper four general models of family size are developed and utilized for classifying previous work on the micro economic analysis of fertility. The general models describe four family decision-making situations. The outcome of these decisions determines fertility either directly or indirectly. In the first model, parents are forced to choose between sexual activity and a higher standard of living. Children are the by products of the amount of sexual activity chosen. In the second model, children are an investment good and family size is determined by the choice between current and future consumption. The third and fourth models depict situations in which children are considered to be desirable in themselves, that is, they are consumption goods. PMID- 22077777 TI - Some principles of cost-benefit analysis of family planning services in developing countries. AB - Summary A number of controversial issues are discussed, relating to the assessment of both costs and benefits of family planning services. All costs and benefits, whether accruing to society or the parents of the child whose birth is averted, and the child itself, should be included in the analysis, even if they cannot easily be measured or appear as externalities. Different rates of interest to be used in discounting to obtain present values apply to various items; these rates may vary between the commercial rates of interest and negative values. It is also shown that the costs of running a service include, in addition to current expenditure, not only basic investments, but also that the benefit accruing to society by averting births comprises a kind of investment, namely the amount spent on the subsistence of the child whose birth is averted before he would have started producing. Marginal values are to be preferred to average values for the calculation of costs and benefits. Thus, the costs of a family planning service should be expressed as the amount of money needed to avert one additional birth and the benefits as the amount saved by one additional averted birth. The latter cannot be measured by comparing the GNP per head when the birth is averted, with the situation when it is not. This can only be done by computing the excess of the child's life-time consumption over his life-time production. PMID- 22077776 TI - The influence of human fertility on the economic conditions of the rural population in poland. AB - Summary In 1970, Polish women in agricultural households reported larger numbers of children born alive than women in other occupations. When controlling for the influence of age at marriage and duration of marriage, the average number of children born per women among the farming population increased directly with the amount of privately owned agricultural land. Consistently, women whose principal source of livelihood was derived from non-agricultural sources even though they resided in villages, showed lower fertility than those in the agricultural sector, but significantly higher fertility than city women. This study is based on the five per cent sample of ever-married women between 15 and 70 years of age interviewed about their past reproductive histories in Poland during the 1970 Census of Population.The conclusions identify the high level of human fertility in rural populations as the main determinant of economic status among Polish peasants whose sources of support derive primarily from farming. Additional evidence supporting the hypothesis of dependence of the agricultural economy on the force of human reproduction is based on data for Slovakia and the Czech regions. PMID- 22077778 TI - Migration and fertility in Ticino. AB - Summary Migration in the Swiss canton of Ticino is one example of the wide variety of demographic systems that existed in pre-industrial Europe. The continuous movement of men was a consequence of economic, social and geographic conditions which restricted the demand for labour. Seasonal migration and overseas migration were both sex and age selective. They resulted in an imbalance of the sex ratio and a remarkably low female nuptiality. They also reduced fertility within marriage by separating husbands and wives during their childbearing years. The effect of long, medium and short-term migration on fertility can be isolated from census and vital registration sources. PMID- 22077779 TI - Population dynamics and drought: A village in Niger. AB - Summary The paper reports the results of demographic research in a rural village of about 1500 Hausaspeaking farmers in southern Niger, during the winter of 1973-74. The research site lies at the heart of the Sahel-sudanic zone just to the south of the Sahara, where drought, and in some areas, famine have exacted a heavy human, animal, and economic toll since 1968. The study was designed to measure and explain the change in the size and structure of the population during the years 1969-73. Social anthropological field techniques were used to ensure full and accurate reporting by community residents on all census topics. Data on rainfall and crop yields, on health and sanitary conditions, and on the political economy, social organization, and culture of the village were gathered in order to interpret the demographic situation The analysis of this data yields the following conclusions: 1. The population of the village appears younger (mean age: 15 years) and growing faster (mean doubling time: 23 years) than reported for Niger as a whole in 1972. 2. Contrary to what the researchers expected, the crude death rate, while relatively high to begin with, actually declined during the drought period (mean: 14.81); the crude birth rate remained very high (mean: 46.01), and the crude rate of increase rose from 1969 to 1973. 3. There was virtually no family out-migration from the target village during the drought, although the number of adult males participating in seasonal migrations to large West African towns rose from 35 per cent in 1969-70 to 75 per cent in 1973-74. 4. Problems of food production and distribution were acute, but thanks to the availability of donated foods, these were sufficiently short-lived during this drought cycle to make no discernible impact on population, although prolonged protein/calorie malnutrition among the very young may affect future fecundity. PMID- 22077780 TI - Child survival and intervals between pregnancies in Guayaquil, Ecuador. AB - Summary Intervals between births to 1934 women from poor areas of Guayaquil, Ecuador, were subjected to analysis to determine what effect on survival chances of their children, if any, was exerted by differences in these intervals. The analysis showed that risks of miscarriage and stillbirth were increased when the interval between last termination of pregnancy and conception was either very short or very long. Post-neo-natal mortality was strongly influenced by the length of the interval, reaching a minimum where the interval was around three years. The influence of interval length diminished as the level of mortality fell (with improving health standards over time). The possibility could not be discarded that for neo-natal mortality and mortality in the second year of life, extremely short intervals (under three months) carried significant additional risks. For both periods, intervals longer than three years increased the risk of infant mortality. Evidence was found that the survival chances of the first child of a pair were seriously impaired during the first year of life where a fresh conception supervened during that period (the earlier this happened the more serious the impairment). An analysis of'double intervals' (not presented here) showed that the effects of short intervals were exaggerated when two such intervals succeeded one another. The principle conclusions remained valid when competing sources of association between short intervals and mortality were excluded, thus lending plausibility to the view that the two are connected by a causal chain. While no great precision can be claimed, it seems likely that if effective measures were taken to prevent the occurrence of pregnancy intervals shorter than 27 months (corresponding to birth intervals of less than three years) spontaneous abortions might be reduced by one-third and infant mortality by one-half in populations similar to that studied here. These results justify a recommendation that the prescription of contraception for a limited period post partum in areas of moderate or high neo-natal mortality should become a routine of responsible obstetric or maternity and child welfare care. PMID- 22077781 TI - Comments on R. H. Gray's 'The decline in mortality in Ceylon and the demographic effects of malaria control'. AB - Abstract With his article 'The Decline in Mortality in Ceylon and the Demographic Effects of Malaria Control', R. H. Gray has added a new contribution to the long discussion of the effects of malaria eradication on the abrupt mortality decline experienced by Ceylon immediately after World War II. He has used new information and at the same time introduced slight modifications in the statistical procedures designed to evaluate the validity of the hypothesis. However, certain aspects of his article need to be clarified; they are related to the methodology employed and to the theoretical approach used. PMID- 22077782 TI - A reply to Mr Palloni's comments. AB - Abstract The protracted and inconclusive debate on the cause of the post-war mortality decline in Ceylon reflects our ignorance of this complex historical event and although I am reticent to prolong this already lengthy discussion, I feel that it is necessary to reply to certain points raised by Mr Palloni. The object of my paper 'The Decline of Mortality in Ceylon and the Demographic Effects of Malaria Control'(9) was to re-examine some of the past work on this subject in order to attempt a synthesis of previous theories, was not, however, intended to provide a definitive account of all the causal mechanisms underlying the decline of mortality as it is my view that the data are insufficient for such an undertaking. In the reappraisal I was mainly concerned with the validity of Newman's regression model and, as far as the data would permit, an assessment of Meegama's thesis that there were significant disturbing variables which confounded the simple regression of mortality decline and malaria prevalence. I will try first to respond to Mr Palloni's specific substantive points and then go on to consider the broader question of regression models. PMID- 22077785 TI - Bovine paratuberculosis: recent advances in vaccine development. AB - Bovine paratuberculosis is a highly prevalent chronic infection of the small intestine in cattle, caused by Mycobacterium avium subspecies paratuberculosis. Current control strategies based on test-and-cull and biosecurity measures do not suffice in lowering the prevalence of paratuberculosis in an adequate manner. Therefore, control programmes are in need of an effective vaccine, but at the moment no vaccine is registered for use in cattle in the European Union. This review provides a brief overview of the microbiology, epidemiology and immunology of bovine paratuberculosis, and focuses on recent advances in the development of vaccines against paratuberculosis. PMID- 22077786 TI - General application of the National Institute for Health and Clinical Excellence (NICE) guidance for active surveillance for men with prostate cancer is not appropriate in unscreened populations. PMID- 22077787 TI - Leucine-rich repeat kinase 2 (LRRK2) cellular biology: a review of recent advances in identifying physiological substrates and cellular functions. AB - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common forms of inheritable Parkinson's disease and likely play a role in sporadic disease as well. LRRK2 is a large multidomain protein containing two key groups, a Ras-like GTP binding domain and a serine, threonine kinase domain. Mutations in the LRRK2 gene that associate with Parkinson's disease reside primarily within the two functional domains of the protein, suggesting that LRRK2 function is critical to the pathogenesis of the disease. The most common LRRK2 mutation increases kinase activity, making LRRK2 kinase inhibition an attractive target for small molecule drug development. However, the physiological function of LRRK2 kinase as well as its endogenous protein substrates remains poorly understood and has hindered drug development efforts. Recent advances in LRRK2 biology have revealed several potential cellular roles, interacting proteins, and putative physiological substrates. Together, a picture emerges of a complex multifunctional protein that exists in multiple cellular compartments. Through unclear mechanisms, LRRK2 kinase regulates cytoskeleton architecture through control of protein translation, phosphorylation of cytoskeletal proteins, and response to cellular stressors. This article will briefly cover some interesting recent studies in LRRK2 cellular biology and highlight emerging cellular models of LRRK2 kinase function. PMID- 22077788 TI - Serial developmental assessments in infants with deformational plagiocephaly. AB - AIM: An association between positional plagiocephaly and developmental problems has previously been noted, but whether delays persist over time has not been established. This study aimed to determine developmental outcomes for children with deformational plagiocephaly over 1 year of follow up. METHODS: This was a longitudinal cohort study of 126 infants with deformational plagiocephaly recruited at an outpatient clinic. Development was assessed with the parent completed Ages and Stages Questionnaires at recruitment and repeated at follow-up assessments in the home 3, 6 and 12 months later. Questionnaires were scored according to cut-off scores from the Ages and Stages Questionnaires, Third Edition. RESULTS: Ninety-six percent of children were followed up for the full 12 months. The existence of one or more delays initially was 30%; this rose to 42% at the 3-month follow up then dropped back to 23% by the 12-month follow up. Delays were predominantly in the gross motor domain. Ten percent had > 4 delays in total over the four assessments. Mothers with tertiary education were more likely to have infants showing delays that persisted over time. CONCLUSIONS: Infants with deformational plagiocephaly exhibited marked delays especially in early infancy. These delays were largely gross motor in type but had reduced to approach the expected level by the time of the 12-month follow up, at a mean age of 17 months. PMID- 22077789 TI - A population-based breast cancer screening programme: conducting a comprehensive survey to explore adherence determinants. AB - This research examines several important individual and environmental variables that can predict breast cancer screening practices among Portuguese women aged 45 69 years old, under a population-based programme. A cross-sectional study was conducted to a convenience sample with 805 women in Aveiro municipality. Survey interviews were applied to adherents and non-adherents in two different settings (health centre, home places). A combination of bivariate (chi-squared test) and multivariate analysis [decision tree by the chi-squared automatic interaction detection (CHAID) algorithm] was performed to determine differences between the groups and predict the variables. Findings showed that there is a significant association between almost all 29 indicators with adherence and non-adherence. Younger women (<50 years) with 'concordant' Behaviour Profile to the guidelines are those who adhere more in comparison with the other age groups. On the other hand, those with non-adherent behaviour need to have a 'good' attendance of healthcare providers for becoming adherents to the screening programme. Multiple strategies that combine enhancing primary health care access, individual behaviour and knowledge must be addressed to uptake adherence. In this way, the health teams must act in accordance with the guidelines, targeting more effective health education practices to achieve the goals of the breast cancer screening. PMID- 22077790 TI - Second-generation platelet concentrate (PRF) as a pulpotomy medicament in a permanent molar with pulpitis: a case report. AB - AIM: To discuss the clinical and radiographic success of a pulpotomy with second-generation platelet concentrate (PRF), in a human mature permanent molar tooth. SUMMARY: A 19-year-old female patient reported to the Department of Conservative Dentistry and Endodontics with established pulpitis in tooth 36. The tooth had a carious pulp exposure, with a history of lingering pain. After isolation, caries removal and pulp exposure, pulpotomy with PRF was performed and a permanent restoration was placed immediately. At the first recall (+1 day), no postoperative pain was reported. At 6, 12, 18 and 22 months recall, the tooth responded positively to pulp sensibility tests, and radiographic examination revealed a normal periodontal ligament space. Positive results of this case imply the need for more studies with larger sample sizes and a longer recall period to justify the use of this novel material for the treatment of pulpitis in human permanent molar teeth. KEY LEARNING POINTS: Pulpotomy with PRF could be an alternate treatment to mineral trioxide aggregate or other materials in mature permanent teeth with pulpitis. PMID- 22077791 TI - Relationships between Geriatric Oral Health Assessment Index scores and general physical status in community-dwelling older adults. AB - OBJECTIVE: The aim of this study was to investigate the relationships between Geriatric Oral Health Assessment Index (GOHAI) and general physical status among community-dwelling older adults. BACKGROUND: Geriatric Oral Health Assessment Index is a patient-centred assessment of oral health for older adults. We hypothesised that GOHAI is a significant indicator of general physical status of older adults. METHODS: This study included 354 adults (age, >=65 years) living independently. Body mass index, handgrip strength and one-leg standing time with eyes open were used to evaluate the general physical status. Spearman's rank correlation coefficients were calculated to examine the relationships between the GOHAI scores, its three subdivided categories (physical function, psychological function and pain and discomfort) and each physical status measurement. A stepwise linear regression model was applied with each physical status measurement as the dependent variable and the GOHAI scores and its subdivisions as the principal independent variable. RESULTS: Positive correlations were found between the GOHAI scores, its three subdivided categories and handgrip strength. The physical function category positively correlated with one-leg standing time. The GOHAI and the pain and discomfort category scores were retained in the final models of stepwise regression for handgrip strength, and significant relationships persisted after adjustments for demographic, psychosocial, medical and dental status. CONCLUSION: The GOHAI scores and its pain and discomfort category score may be significant indicators of body muscle strength. PMID- 22077792 TI - Reviews on animal diseases recently published in other journals. PMID- 22077794 TI - Fotemustine for the treatment of melanoma. AB - INTRODUCTION: Melanoma is a rare but very aggressive form of cancer. Survival in melanoma varies widely depending on the stage of the tumor. In metastatic melanoma, prognosis is usually poor and the treatment is based on chemotherapy. So far, dacarbazine has been the drug of reference, with an average response rate of 15 - 20% when used as a monotherapy. As single drugs go, fotemustine is considered the second-best treatment, after dacarbazine. AREAS COVERED: This review of the scientific literature focuses on the use of fotemustine in patients with cutaneous melanoma and discusses its clinical efficacy and safety. EXPERT OPINION: Fotemustine is a nitrosurea that has proved its efficacy in metastatic melanoma and particularly on cerebral metastases, given its high lipophilicity, facilitating its active penetration in all tissues including the central nervous system. However, overall response rates are low, with only few complete remissions and short response durations. PMID- 22077795 TI - Design and synthesis of new antioxidants predicted by the model developed on a set of pulvinic acid derivatives. AB - Antioxidative activity expressed as protection of thymidine has been investigated for a set of 30 pulvinic acid derivatives. A combination of in vitro testing and in silico modeling was used for synthesis of new potential antioxidants. Experimental data obtained from a primary screening test based on oxidation under Fenton conditions and by an UV exposure followed by back-titration of the amount of thymidine remaining intact have been used to develop a computer model for prediction of antioxidant activity. Structural descriptors of 30 compounds tested for their thymidine protection activity were calculated in order to define the structure-property relationship and to construct predictive models. Due to the potential nonlinearity, the counter-propagation artificial neural networks were assessed for modeling of the antioxidant activity of these compounds. The optimized model was challenged with 80 new molecules not present in the initial training set. The compounds with the highest predicted antioxidant activity were considered for synthesis. Among the predicted structures, some coumarine derivatives appeared to be especially interesting. One of them was synthesized and tested on in vitro assays and showed some antioxidant and radioprotective activities, which turned out as a promising lead toward more potent antioxidants. PMID- 22077797 TI - Faradaurate nanomolecules: a superstable plasmonic 76.3 kDa cluster. AB - Information on the emergence of the characteristic plasmonic optical properties of nanoscale noble-metal particles has been limited, due in part to the problem of preparing homogeneous material for ensemble measurements. Here, we report the identification, isolation, and mass spectrometric and optical characterization of a 76.3 kDa thiolate-protected gold nanoparticle. This giant molecule is far larger than any metal-cluster compound, those with direct metal-to-metal bonding, previously known as homogeneous molecular substances, and is the first to exhibit clear plasmonic properties. The observed plasmon emergence phenomena in nanomolecules are of great interest, and the availability of absolutely homogeneous and characterized samples is thus critical to establishing their origin. PMID- 22077796 TI - A tool kit for measuring functioning in children with neurodisability: calibrating activities. PMID- 22077798 TI - Filamentous actin is a substrate for protealysin, a metalloprotease of invasive Serratia proteamaculans. AB - Homologous bacterial metalloproteases ECP32/grimelysin from Serratia grimesii and protealysin from Serratia proteamaculans are involved in the invasion of the nonpathogenic bacteria in eukaryotic cells and are suggested to translocate into the cytoplasm [Bozhokina ES et al. (2011) Cell Biol Int35, 111-118]. The proteases have been characterized as actin-hydrolyzing enzymes with a narrow specificity toward intact cell proteins. However, cleavage of filamentous actin (F-actin) (i.e. the main actin species in the cell) and the properties of the cleaved F-actin have not been investigated previously. In the present study, we revealed the presence of protealysin in the cytoplasm of 3T3-SV40 cells infected with S. proteamaculans or recombinant Escherichia coli expressing the protealysin gene. We also show for the first time that purified protealysin and the lysates of the recombinant E. coli producing protealysin cleave 20-40% of F-actin. Cleavage limited predominantly to the bond Gly42-Val43 efficiently increases the steady-state ATPase activity (dynamics) of F-actin. abolishes this effect and promotes the nucleation of protealysin-cleaved Mg-globular-actin even in the absence of 0.1 m KCl, most likely as a result of the stabilization of lateral intermonomer contacts of actin subunits. The results obtained in the present study suggest that F-actin can be a target for protealysin upon its translocation into the host cell. PMID- 22077799 TI - Poly(3-hexylthiophene)/TiO2 nanoparticle-functionalized electrodes for visible light and low potential photoelectrochemical sensing of organophosphorus pesticide chlopyrifos. AB - A dramatic visible light photoelectrochemical sensing platform for the detection of pesticide molecules at zero potential (versus saturated calomel electrode) was first constructed using poly(3-hexylthiophene)-functionalized TiO(2) nanoparticles. Poly(3-hexylthiophene) (P3HT) was synthesized via chemical oxidative polymerization with anhydrous FeCl(3) as the oxidant, 3-hexylthiophene as the monomer, and chloroform as the solvent, and the functional TiO(2) nanoparticles were facilely prepared by blending TiO(2) nanoparticles and P3HT in chloroform solution. The resulting photoelectrocatalysts were characterized by scanning electron microscopy, Raman spectroscopy, and X-ray diffractometry. Under visible light irradiation, P3HT generated the transition from the valence band to the conduction band, delivering the excited electrons into the conduction band of TiO(2) and then to the glassy carbon electrode. Simultaneously, a positive charged hole (h(+)) of TiO(2) may form and migrate to the valence band of P3HT, which can react with H(2)O to generate (*)OH, and then it converted chlopyrifos into chlopyrifos(*) that promoted the amplifying photocurrent response. On the basis of the proposed photoelectrochemical mechanism, a methodology for sensitive photoelectrochemical sensing for chlopyrifos at zero potential was thus developed. Under optimal conditions, the proposed photoelectrochemical method could detect chlopyrifos ranging from 0.2 to 16 MUmol L(-1) with a detection limit of 0.01 MUmol L(-1) at a signal-to-noise ratio of 3. The photoelectrochemical sensor had an excellent specificity against the other pesticides and could be successfully applied to the detection of reduced chlopyrifos in green vegetables, showing a promising application in photoelectrochemical sensing. PMID- 22077801 TI - The emotional cost of charitable donations. AB - Donations in support of a charitable cause can create a conflict between moral intuitions (e.g., fulfilling moral obligations and helping as many individuals in need as possible) and the cost entailed by following one's moral intuitions (e.g., spending money). The present paper investigates this conflict by putting people in a situation in which they must choose whether to help three women by giving more money or help one woman by giving less. In addition, the paper uses the attraction effect paradigm to counteract the single victim effect and reduce the conflict. Experiment 1 demonstrates that in a two-alternative context the majority of participants choose to help one woman by giving ?150 instead of helping three women by giving ?450. Experiment 2 replicates this finding and highlights the role of emotion regulation strategies in the management of the emotional conflict arising in the two-alternative condition. In both studies, the introduction of a third, dominated alternative reduces the conflict and makes it easier to choose the programme asking for a higher donation and helping three women. Implications for charitable donations and the role of the conflict between moral intuitions and economic costs are discussed. PMID- 22077800 TI - Fluorescent acridine-based receptors for H2PO4(-). AB - Two new pseudopeptidic molecules (one macrocyclic and one open chain) containing an acridine unit have been prepared. The fluorescence response of these receptors to a series of acids was measured in CHCl(3). Receptors are selective to H(2)PO(4)(-) versus HSO(4)(-), and an even higher selectivity is found over other anions such as Cl(-), Br(-), CH(3)COO(-), and CF(3)COO(-). We show that the macrocyclic receptor is more selective for H(2)PO(4)(-) than the related open chain receptor. The supramolecular interactions of triprotonated receptors with different anions have been modeled in silico and have been studied by different experimental techniques. Optimized geometries obtained by computational calculations agree well with experimental data, in particular fluorescence experiments, suggesting that the selective supramolecular interaction takes places through coordination of the anions to the triprotonated form of the receptor. PMID- 22077802 TI - Nuptiality patterns in an agrarian society. AB - Summary The paper deals with the non-European marital pattern and its determinants in an agrarian society before the onset of deliberate fertility decline. A wide range of patterns, from very early and almost universal to late marriage, existed among the populations of European Russia at the end of the nineteenth century. The analysis confirmed a close association, particularly between marital behaviour and socio-economic institutions. Scarcity of labour relative to land, the principle of landholding and land usage according to the amount of labour in the extensive type of family, and an equal-heir inheritance system were found to be conducive to early and common marriage. The spatial differentiation of marital patterns was found to be due to regional modifications in the above institutions, the degree of literacy, size of rural settlements, industrial and urban development, and the sex composition. PMID- 22077803 TI - Intermediate fertility variables and marital fertility rates. AB - Summary Using relatively simple mathematical techniques, an analysis is made of a comprehensive reproductive model that describes the relationships between a set of intermediate fertility variables and the marital fertility rate. Two types of intermediate fertility variables are distinguished: (1) biological parameters and (2) control variables. A homogeneous model is outlined first. Next, this version is extended to include heterogeneity with respect to fecundability and coital rates. Tests of the model with data from two historical populations (i.e. Crulai, 1674-1742, and Tourouvre au Perche, 1665-1765) demonstrate that the model is, indeed, consistent with observed reproductive behaviour in actual populations. PMID- 22077804 TI - An economist's non-linear model of self-generated fertility waves. AB - Summary Standard one-sex linear models of Lotka or Bernardelli always approach asymptotically an exponential growth mode with stable age distribution. Realistic non-linear models need not possess this property. The present analysis uncovers a possibly realistic ease where an existent mode of balanced growth is 'unstable', giving way when slightly perturbed to an asymptotic every-other generation limit cycle of determinable amplitude, and which is stable. The nonlinear model utilizes the hypothesis of R. A. Easterlin that age-specific fertility will tend to be lower for age classes that are relatively swollen in total number. By virtue of the law of diminishing returns, wages and feeling of security will tend to be low for such swollen groups. A possible rebound in fertility in the 1980s is implicit in the Easterlin hypothesis. PMID- 22077805 TI - The effect of child mortality experience on subsequent fertility: in Pakistan and Bangladesh. AB - Summary This paper presents an empirical analysis of the effects, behavioural and biological, of child mortality experience on subsequent fertility in two South Asian Islamic nations. Data for the investigation came from retrospective pregnancy histories of 2,910 currently married women interviewed in the Pakistan National Impact Survey (1968-69) and from longitudinal vital registration data (1966-2070) of 5,236 women residing in a rural area of Bangladesh collected by the Cholera Research Laboratory. The aim of this study was to assess the importance of the child-replacement motivational response to child death experience after biological effects have been controlled adequately. A common approach employed previously has been to examine cumulative fertility according to child death experience. In Pakistan and Bangladesh, a consistently positive relationship was demonstrated between the number of children ever born and the number of child deaths. This method, however, did not exclude the inverse relationship, the influence of fertility on mortality, nor did it dissect out behavioural from biological effects. Utilizing a measure of subsequent fertility, live-birth-to-live-birth intervals, the study further illustrated another common pitfall. Since the risk of infant death, which leads to shorter birth intervals, is associated with the mother's reproductive history, women with child mortality experience are more likely to experience shorter intervals because of the biological effect of subsequent infant death. Behavioural influences may, therefore, be observed by considering only those birth intervals in which the first-born child survives to the end of the interval. With these limitations controlled, very few, if any, behavioural influences were noted in the Pakistan and Bangladesh data. Median birth intervals in Pakistan varied between 35-43 and 41-42 months, increasing with parity. Within each parity group, no consistent difference was observed between women with and without previous child loss. In Bangladesh, the median birth interval for all women with a surviving infant was 37-2 months. This was shortened to 24-31 months by an infant death. When intervals with infant deaths were excluded, little or no behavioural influence was detected among women of the same parity, but with varying levels of previous child loss. Even without behavioural effects, elimination of infant mortality in Bangladesh would reduce fertility by prolonging the average period of post-partum sterility. In the Bangladesh setting, however, the size of the effect was only about four per cent. This modest effect, more-over, was counterbalanced by an overall increase of net reproduction by seven per cent due to better survivorship of infants. PMID- 22077806 TI - The child survival hypothesis. AB - Summary Because of current interest in the child survival hypothesis, we have reviewed available evidence bearing upon the relationships of infant and child mortality to fertility and contraceptive behaviour. The evidence is drawn from time series data for local and national vital events, from special in-depth studies of the infant mortality-fertility relationships in family formation, and from service statistics from health and family planning programmes. As a result of this review, we suggest five clarifications which should be made in redefining the child survival hypothesis and assessing its potential programme implications. The child survival hypothesis states that improved child survival will contribute to increased family planning motivation and consequent fertility decline. The evidence presented here suggests that the effect is not automatic and probably not a necessary pre-condition for fertility decline. There is certainly not a reflexive one-to-one replacement, but a partial effect may still be important. In the clearly demonstrated reduction in inter-pregnancy intervals after a child death, the major component is undoubtedly the removal of the biological protection of lactational amenorrhoea. A separate but somewhat smaller effect has been demonstrated in situations where lactation did not seem to have been the explanation. It is expected that increased child survival will contribute to fertility decline mainly in countries experiencing rapid mortality decline and population growth. The replacement of children who die is probably not so much 'volitional' as a result of alterations in sub-conscious expectations. It is apparent that in traditional agrarian populations, few direct and manipulable means of influencing motivation for fertility limitation are available, and, therefore, it must be stressed that integrated health and family planning programmes do provide opportunities for immediate programme development. By making parents aware of improved changes of survival through health services in which they develop confidence, the spontaneous linkages between mortality and fertility can presumably be reinforced. Family planning services must be provided as an essential initial step in programme development, but they can be made more effective, as well as politically more acceptable if appropriately integrated with maternal and child health and nutrition services. PMID- 22077807 TI - Infant mortality and birth intervals. AB - Summary In the course of a demographic inquiry which also offered medical advice to the respondent women, information was obtained on the reproductive life and child mortality of women in three regions of Upper Volta. Foetal mortality rates are inversely correlated with fertility rates, whereas the opposite holds true of the mortality of children aged up to four years. An explanation of this phenomenon is attempted, showing how large variations in mortality rates continue to exist in developing countries. The second section of the paper deals with spontaneous abortions which happen much more frequently than is believed in Black Africa and with the effect of pathological sterility on birth intervals. Account is taken of the taboo on sexual relations after children have been born, a taboo which continues to be kept in the region studied and which as an important effect on inter-birth intervals. PMID- 22077808 TI - Purposive concealment of death in household surveys in Misamis Oriental Province. AB - Summary The randomized response technique was used in a household survey of approximately 2,000 rural and 2,000 urban households in Misamis Oriental Province in the southern Philippines in order to determine the extent of purposive concealment of death. The estimated number of deaths deliberately not revealed to the interviewers was 50 per cent or higher. Adjusted crude death rates of 11.5 and 13.4 per 1,000 population were computed for urban and rural areas, respectively, by adding estimated concealed deaths to deaths reported to the interviewers. Application of stable population techniques and of model life tables suitable to the Philippine setting, while not permitting definite conclusions, provided reasons for believing that these adjusted death rates are close to the true mortality situation in the study areas. Randomized response data further indicate that approximately 75 per cent of urban deaths and 47 per cent of rural deaths of the population studied were not registered with municipal authorities. The authors postulate that failure to register deaths with municipal authorities, together with fear of legal involvement if this failure becomes known outside the immediate neighbourhood, is a major reason for the purposive concealment of death in household surveys. PMID- 22077809 TI - Facts and artifacts in the study of intra-uterine mortality: A reconsideration from pregnancy histories. AB - Summary The analysis of intra-uterine mortality is made difficult by the interaction of many factors, some of them being pure artifacts resulting from the way in which the data are collected, or from the under-reporting of induced abortions. This paper deals with some 'real factors' of variation in the risk of spontaneous abortion (mother's age, pregnancy order, number of previous abortions), and with some of these 'artifacts' (inclusion of induced abortion, memory effect, differential continuation rates). Special attention is paid to the effect of heterogeneity of the risk of abortion. After a discussion of problems of observation, data from two different samples are analysed, first in a classic way: variation with age and pregnancy order, comparison between the rates of abortion for current and previous abortion. Next, detailed data on successive pregnancies are used to derive estimates of the distribution of risk between women. It is concluded that this distribution could and should be taken into account, and that its effects are different from those of age. The possibility of differential continuation rates by outcome of pregnancy is discussed briefly, in connection with previous points. PMID- 22077810 TI - Population planning in Asia in the 1970s. AB - Summary To what extent is family planning integrated with broader population planning in the countries of East Asia and South Asia? To what degree do these countries combine population planning with economic and social planning in their development plans? An attempt to answer these questions suggests that, despite variability from country to country in development goals and policy implementation, family planning has been largely separated from economic planning, and birth control programmes have often been substituted for intermediate and long-range population planning. Demographic factors have been treated as exogenous variables rather than as integral parts of social-economic demographic plans. Such comprehensive planning is difficult for both technical and political reasons, but in any case is unlikely to be achieved so long as family planning and population planning continue to be confused. PMID- 22077813 TI - Erratum: Systematic and chance components in fertility measurement. PMID- 22077811 TI - Extrapolation of IUD continuation curves. AB - Summary Calculation of the number of contraceptive acceptors needed to register predesignated effects on birth or growth rates presupposes that it is known for how long couples practise each contraceptive method. Life table techniques may be used to estimate proportions continuing with a given method: but most follow-up studies yield data for durations no longer than from two to three years. To estimate continuation rates for the longer durations relevant to a five-or ten year target period, the curve of continuation must be extrapolated. Four functions, including the one most commonly used and three new ones, are compared on the basis of data from the Taichung IUD Follow-up Study that commands an effective observation period of eight years. This unusual length makes it possible to perform the experiment of pretending that observation length is only one, two, ... five years and then compare results based on these varyingly abbreviated spans with those based on the full observation period. No one of the four functions is found to be ideal under all circumstances. A strategy for choosing among the functions is suggested. PMID- 22077814 TI - Photocatalytic synthesis of urea from in situ generated ammonia and carbon dioxide. AB - TiO(2) and Fe-titanate (different wt%) supported on zeolite were prepared by sol gel and solid-state dispersion methods. The photocatalysts prepared were characterized by X-ray diffraction, scanning electron microscopy and ultraviolet (UV)-visible diffuse reflectance spectroscopy techniques. Photocatalytic reduction of nitrate in water and isopropanol/oxalic acid as hole scavengers are investigated in a batch reactor under UV illumination. The yield of urea increased notably when the catalysts were supported on zeolite. The Fe-titanate supported catalyst promotes the charge separation that contributes to an increase in selective formation of urea. The product formation is because of the high adsorption of in situ generated CO(2) and NH(3) over shape-selective property of the zeolite in the composite photocatalyst. The maximum yield of urea is found to be 18 ppm while 1% isopropanol containing solution over 10 wt% Fe-titanate/HZSM-5 photocatalyst was used. PMID- 22077815 TI - Operating theatre nurses' experience of patient-related, intraoperative nursing care. AB - The way patient-related, intraoperative nursing care is performed by operating theatre nurses' has not been elucidated in any great detail. The aim of this study therefore was to describe theatre nurses' experience of patient-related, intraoperative nursing care. The study draws on qualitative, interpretive description methodology. Sixteen specialists in operating theatre nursing care, working in rural or metropolitan hospitals in Sweden, were included in the study. Data were collected by means of interviews and analysed using an inductive, qualitative, descriptive analysis technique. The data analysis resulted in 15 overarching nursing care procedures and three motives for nursing care procedures in the field of intraoperative nursing care with the goal of achieving the best surgical outcome for the patient. The operating theatre nurses' experience of patient-related, intraoperative nursing care was described as procedures to create a continuous, confidence-based relationship and situation-related well being; procedures to guarantee patient safety and well-being by keeping a watchful eye; and procedures to create a secure environment that promotes wound healing, recovery and well-being. PMID- 22077817 TI - Long-term expression of human coagulation factor VIII in a tolerant mouse model using the phiC31 integrase system. AB - We generated a mouse model for hemophilia A that combines a homozygous knockout for murine factor VIII (FVIII) and a homozygous addition of a mutant human FVIII (hFVIII). The resulting mouse, having no detectable FVIII protein or activity and tolerant to hFVIII, is useful for evaluating FVIII gene-therapy protocols. This model was used to develop an effective gene-therapy strategy using the phiC31 integrase to mediate permanent genomic integration of an hFVIII cDNA deleted for the B-domain. Various plasmids encoding phiC31 integrase and hFVIII were delivered to the livers of these mice by using hydrodynamic tail-vein injection. Long-term expression of therapeutic levels of hFVIII was observed over a 6-month time course when an intron was included in the hFVIII expression cassette and wild-type phiC31 integrase was used. A second dose of the hFVIII and integrase plasmids resulted in higher long-term hFVIII levels, indicating that incremental doses were beneficial and that a second dose of phiC31 integrase was tolerated. We observed a significant decrease in the bleeding time after a tail-clip challenge in mice treated with plasmids expressing hFVIII and phiC31 integrase. Genomic integration of the hFVIII expression plasmid was demonstrated by junction PCR at a known hotspot for integration in mouse liver. The phiC31 integrase system provided a nonviral method to achieve long-term FVIII gene therapy in a relevant mouse model of hemophilia A. PMID- 22077819 TI - Screening urine analysis before bacille Calmette-Guerin instillation does not reduce the rate of infectious complications. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Infectious complication is a risk of bacille Calmette-Guerin instillation. Urine analysis in asymptomatic patients has been used as a measure to reduce infections. This study suggests that screening urine analysis prior to bacille Calmette-Guerin instillation did not affect the rate of urinary tract infections. OBJECTIVE: * To discover if the routine use of urine analysis decreases the rate of urinary tract infection (UTI) complications after bacille Calmette-Guerin (BCG) administration. METHODS: * A retrospective review of the outcomes of 202 patients undergoing BCG treatment for bladder cancer at two medical centres with different pre-BCG screening strategies was performed. * The medical records of 100 patients who received BCG by one urologist at Memorial Sloan-Kettering Cancer Center (MSKCC) were reviewed. No patient received a urine analysis immediately prior to BCG treatment. * Similarly, 102 patients who received BCG at Northwestern Memorial Hospital (NMH) were reviewed. Patients at NMH were screened by urine analysis for pyuria and bacteriuria before BCG treatment, and, if clinically indicated, BCG instillation was delayed for the results of the urine culture. * If the urine culture confirmed infection, then the patient was treated before restarting BCG instillation. RESULTS: * At MSKCC, 100 patients underwent 600 BCG treatments. * After BCG administration, symptomatic UTI occurred in three patients (3%), successfully treated with antibiotics. * No patients developed BCG sepsis or required hospitalization due to infection. * At NMH, 102 patients underwent 612 BCG treatments. * Pre-BCG urine analysis was positive for pyuria (defined as white blood cells >5 per high-power field) in 27.8%, and positive for bacteriuria (defined as any bacteria on microscopy) in 18.1%. * Based on the results of pre screening urine analysis, BCG instillation was delayed 15 times (2.5%). * Overall, three patients (3%) had culture-proven UTIs after BCG instillation. * No patients developed BCG sepsis or required hospitalization in either group and there were no significant differences in the frequency of UTIs. CONCLUSIONS: * Urine analysis can safely be omitted before administration of BCG in asymptomatic patients. * Omission of urine analysis could save time and expense during the office-based treatment of bladder cancer. PMID- 22077818 TI - Maternal pre-pregnant body mass index, maternal weight change and offspring birthweight. AB - OBJECTIVE: To estimate the association between maternal pre-pregnant body mass index (BMI) and maternal weight change during pregnancy and offspring birthweight using the BMI classification developed by World Health Organization (WHO) and adopted by the Institute of Medicine (IOM) in 2009. DESIGN: The Norwegian Mother and Child Cohort Study (MoBa) is a population-based pregnancy cohort study conducted by The Norwegian Institute of Public Health. SETTING: Women were recruited from all geographic areas of Norway. POPULATION: The study includes 58,383 pregnant women. METHODS: Women were enrolled in 2000-2007 by a postal invitation offered to women in Norway at 17-18 weeks of gestation. Linear regression analyses are based on exposure data from two questionnaires during pregnancy and on birthweight data. MAIN OUTCOME MEASURES: Birthweight. RESULTS: Mean pre-pregnancy BMI was 24kg/m(2) (SD 4.3), mean maternal weight change in the first 30 weeks of gestation was 9.3kg (SD 4.4), mean birthweight was 3675g (SD 487) and mean age 30.3 years. Of the women, 65.2% had a normal pre-pregnancy weight, 2.9% were underweight, 22.3% overweight, and 9.5% obese (Classes 1-3). Linear regression analyses adjusted for potential confounders showed that offspring birthweight increased with increasing maternal pre-pregnant BMI, and with increasing maternal weight gain during pregnancy in all six categories of pre-pregnancy BMI. Women with the highest level of education had the highest offspring birthweight. CONCLUSION: Offspring birthweight increased with both increasing maternal pre-pregnant BMI and maternal weight gain during pregnancy in all six categories of maternal pre-pregnancy BMI. PMID- 22077820 TI - High prevalence of childhood asthma in Northern Israel is linked to air pollution by particulate matter: evidence from GIS analysis and Bayesian Model Averaging. AB - The medical records of 3922 school children residing in the Greater Haifa Metropolitan Area in Northern Israel were analyzed. Individual exposure to ambient air pollution (SO(2) and PM(10)) for each child was estimated using Geographic Information Systems tools. Factors affecting childhood asthma risk were then investigated using logistic regression and the more recently developed Bayesian Model Averaging (BMA) tools. The analysis reveals that childhood asthma in the study area appears to be significantly associated with particulate matter of less than 10 MUm in aerodynamic diameter (PM(10)) (Odds Ratio (OR) = .11; P<0.001). However, no significant association with asthma prevalence was found for SO(2) (P >0.2), when PM(10) and SO(2) were introduced into the models simultaneously. When considering a change in PM(10) between the least and the most polluted parts of the study area (9.4 MUg/m(3)), the corresponding OR, calculated using the BMA analysis, is 2.58 (with 95% posterior probability limits of OR ranging from 1.52 to 4.41), controlled for gender, age, proximity to main roads, the town of a child's residence, and family's socio-economic status. Thus, it is concluded that exposure to airborne particular matter, even at relatively low concentrations (40-50 MUg/m(3)), generally below international air pollution standards (55-70 MUg/m(3)), appears to be a considerable risk factor for childhood asthma in urban areas. This should be a cause of concern for public health authorities and environmental decision-makers. PMID- 22077821 TI - Neoadjuvant and adjuvant chemotherapy for locally advanced bladder carcinoma: development of novel bladder preservation approach, Osaka Medical College regimen. AB - Cisplatin-based chemotherapy has been widely used in a neoadjuvant as well as adjuvant setting. Furthermore, trimodal approaches including complete transurethral resection of the bladder tumor followed by combined chemotherapy and radiation have generally been performed as bladder preservation therapy. However, none of the protocols have achieved a 5-year survival rate of more than 70%. Additionally, the toxicity of chemotherapy and/or a decreased quality of life due to urinary diversion cannot be ignored, as most patients with bladder cancer are elderly. We therefore newly developed the novel trimodal approach of "combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects ("Osaka Medical College regimen" referred to as the OMC regimen). We initially applied the OMC regimen as neoadjuvant chemotherapy for locally advanced bladder cancer. However, since more than 85% of patients with histologically-proven urothelial cancer achieved complete response with no evidence of recurrence after a mean follow-up of 170 (range 21-814) weeks, we have been applying the OMC-regimen as a new approach for bladder sparing therapy. We summarize the advantage and/or disadvantage of chemotherapy in neoadjuvant as well as adjuvant settings, and show the details of our newly developed bladder sparing approach OMC regimen in this review. PMID- 22077822 TI - Short communication: HIV type 1 escapes inactivation by saliva via rapid escape into oral epithelial cells. AB - Saliva contains anti-HIV-1 factors, which show unclear efficacy in thwarting mucosal infection. When incubated in fresh, unfractionated whole saliva, infectious HIV-1 IIIb and BaL (X4- and R5-tropic, respectively) persisted from 4 to at least 30 min in a saliva concentration-dependent manner. In salivary supernatant for up to 6 h, both infectious HIV-1 strains "escaped" into immortalized oral epithelial cells; infectious BaL showed selectively enhanced escape in the presence of saliva. Fluorescently labeled HIV-1 virus-like particles entered oral epithelial cells within minutes of exposure. Using a previously unrecognized mechanism, therefore, strains of HIV-1 escape inactivation by saliva via rapid uptake into oral epithelial cells. PMID- 22077824 TI - Erratum. PMID- 22077823 TI - Editorial. PMID- 22077825 TI - A negative cooperativity mechanism of human CYP2E1 inferred from molecular dynamics simulations and free energy calculations. AB - Human cytochrome P450 2E1 (CYP2E1) participates in the metabolism of over 2% of all the oral drugs. A hallmark peculiar feature of this enzyme is that it exhibits a pronounced negative cooperativity in substrate binding. However the mechanism by which the negative cooperativity occurs is unclear. Here, we performed molecular dynamics simulations and free energy calculations on human CYP2E1 to examine the structural differences between the substrate-free and the enzymes with one and two aniline molecules bound. Our results indicate that although the effector substrate does not bind in the active site cavity, it still can directly interact with the active site residues of human CYP2E1. The interaction of the effector substrate with the active site leads to a reorientation of active site residues, which thereby weakens the interactions of the active substrate with this site. We also identify a conserved residue T303 that plays a crucial role in the negative cooperative binding on the short-range effects. This residue is a key factor in the positioning of substrates and in proton delivery to the active site. Additionally, a long-range effect of the effector substrate is identified in which F478 is proposed to play a key role. As located in the interface between the active and effector sites, this residue structurally links the active and effector sites and is found to play a significant role in affecting substrate access and ligand positioning within the active site. In the negative cooperative binding, this residue can decrease the interactions of the active substrate with the active site by pi-pi stacking which then lowers the hydroxylation activity for the active substrate. These findings are in agreement with previous experimental observations and thus provide detailed atomistic insight into the poorly understood mechanism of the negative cooperativity in human CYP2E1. PMID- 22077826 TI - Preparation of shape-persistent macrocycles with a single pyridine unit by double cross-coupling reactions of aryl bromides and alkynes. AB - A double Sonogashira-type coupling reaction between aryl bromides and alkynes using a catalytic Pd/XPhos (2-dicyclohexylphosphino-2',4',6' triisopropylbiphenyl) system was introduced as an efficient method for the synthesis of shape-persistent macrocycles (SPMs). This approach is advantageous in the synthesis of SPMs with a single pyridine unit. PMID- 22077828 TI - Erratum. PMID- 22077827 TI - "First reports": Recent publications on (aspects) of animal diseases not reported before. PMID- 22077830 TI - Nitrogen-doped graphene: efficient growth, structure, and electronic properties. AB - A novel strategy for efficient growth of nitrogen-doped graphene (N-graphene) on a large scale from s-triazine molecules is presented. The growth process has been unveiled in situ using time-dependent photoemission. It has been established that a postannealing of N-graphene after gold intercalation causes a conversion of the N environment from pyridinic to graphitic, allowing to obtain more than 80% of all embedded nitrogen in graphitic form, which is essential for the electron doping in graphene. A band gap, a doping level of 300 meV, and a charge-carrier concentration of ~8*10(12) electrons per cm2, induced by 0.4 atom % of graphitic nitrogen, have been detected by angle-resolved photoemission spectroscopy, which offers great promise for implementation of this system in next generation electronic devices. PMID- 22077832 TI - Telmisartan: just an antihypertensive agent? A literature review. AB - INTRODUCTION: The modulation of the renin angiotensin aldosterone system (RAAS) is an important pathway in managing high blood pressure, and its overexpression plays a key role in target end-organ damage. Telmisartan is an angiotensin II receptor blocker (ARB) with unique pharmacologic properties, including the longest half-life among all ARBs; this leads to a significant and 24-h sustained reduction of blood pressure. Telmisartan has well-known antihypertensive properties, but there is also strong clinical evidence that it reduces left ventricular hypertrophy, arterial stiffness and the recurrence of atrial fibrillation, and confers renoprotection. AREAS COVERED: This paper reviews telmisartan's pharmacological properties in terms of efficacy for hypertension control and, importantly, focuses on its new therapeutic indications and their clinical implications. EXPERT OPINION: ONTARGET (ongoing telmisartan alone and in combination with ramipril global endpoint trial) demonstrated, that telmisartan confers cardiovascular protective effects similar to those of ramipril, but with a better tolerability. Moreover, recent investigations focused on the capability of telmisartan to modulate the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), an established target in the treatment of insulin resistance, diabetes and metabolic syndrome, whose activation is also correlated to anti inflammatory and, finally, anti-atherosclerotic properties. Telmisartan shows peculiar features that go beyond blood pressure control. It presents promising and unique protective properties against target end-organ damage, potentially able to open a scenario of new therapeutic approaches to cardiovascular disease. PMID- 22077833 TI - Telavancin for the treatment of serious gram-positive infections, including hospital acquired pneumonia. AB - INTRODUCTION: Hospital-acquired pneumonia is a common infection, associated with substantial mortality. Despite the increasing prevalence of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), approved treatment options for this pathogen are limited. AREAS COVERED: This article reviews the pharmacokinetics, dosing, preclinical studies and clinical efficacy, and safety of telavancin, with a particular focus on results from trials in nosocomial pneumonia. PubMed and Congress websites were searched for relevant articles published between 2003 and 2010. EXPERT OPINION: Telavancin is a lipoglycopeptide antibiotic with rapid, bactericidal activity against MRSA, and may provide another option for the treatment of nosocomial pneumonia, owing to Gram-positive pathogens. PMID- 22077831 TI - Blockade of cytotoxic T-lymphocyte antigen-4 as a new therapeutic approach for advanced melanoma. AB - INTRODUCTION: The incidence of melanoma continues to rise, and prognosis in patients with metastatic melanoma remains poor. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) serves as one of the primary immune check points and downregulates T-cell activation pathways. Enhancing T-cell activation by antibody blockade of CTLA-4 provides a new approach to overcome tumor-induced immune tolerance. Recently, anti-CTLA-4 therapy demonstrated significant clinical benefits in patients with metastatic melanoma, which led to the approval of ipilimumab by the FDA in early 2011. AREAS COVERED: The fundamental concepts underlying CTLA-4 blockade-potentiated immune activation are presented in this paper, along with the scientific rationale for and the preclinical evidence supporting CTLA-4-targeted cancer immunotherapy. It also provides an update on clinical trials with anti-CTLA-4 inhibitors and discusses the associated autoimmune toxicity. EXPERT OPINION: Given that overall survival is the only validated end point for anti-CTLA-4 therapy, the clinical implications of the antigen or tumor-specific immunity in patients remain to be clarified. Additional research is necessary to elucidate the prognostic significance of immune-related side effects and significantly optimize the treatment regimens. An improved understanding of the mechanisms of action of CTLA-4 antibodies may also culminate in wide-ranging clinical applications of this new therapy for other tumor types. PMID- 22077835 TI - Catalytically active filaments - pyruvate decarboxylase from Neurospora crassa. pH-controlled oligomer structure and catalytic function. AB - Pyruvate decarboxylase is a key enzyme in organisms whose energy metabolism is based on alcoholic fermentation. The enzyme catalyses the nonoxidative decarboxylation of 2-oxo acids in the presence of the cofactors thiamine diphosphate and magnesium ions. Pyruvate decarboxylase species from yeasts and plant seeds studied to date are allosterically activated by their substrate pyruvate. However, detailed kinetic studies on the enzyme from Neurospora crassa demonstrate for the first time the lack of substrate activation for a yeast pyruvate decarboxylase species. The quaternary structure of this enzyme species is also peculiar because it forms filamentous structures. The complex enzyme structure was analysed using a number of methods, including small-angle X-ray solution scattering, transmission electron microscopy, analytical ultracentrifugation and size-exclusion chromatography. These measurements were complemented by detailed kinetic studies in dependence on the pH. PMID- 22077836 TI - Depression and anxiety in episodic and chronic cluster headache: a pilot study. AB - BACKGROUND: In contrast to migraine and tension-type headache, the psychiatric comorbidities of cluster headache (CH) have not been well-studied. OBJECTIVE: We assessed the presence of depression and anxiety in groups of episodic CH (ECH) and chronic CH (CCH) patients and compared CH patients with and without depression and anxiety. METHODS: Sociodemographics, comorbidities, and selected headache features were ascertained from a clinic-based sample in a cross sectional fashion from January 2007 to July 2010. Active depression and anxiety were assessed using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 7-item (GAD-7) scales. RESULTS: Of 49 CH patients, ECH patients (n=32) had an earlier age of onset and consumed less caffeine than CCH patients (n=17). Rates of depression as defined by a PHQ-9 score >=10 were low in both ECH (6.3%) and in CCH (11.8%) with similar mean PHQ-9 scores (3.1 vs 3.7, P=.69). Rates of anxiety as defined by a GAD-7 score >=10 were also low in both ECH (15.6%) and CCH (11.8%) with similar mean GAD-7 scores (3.8 vs 3.4, P=.76). ECH patients in and out of active attack periods had similar levels of depression and anxiety. Depression and anxiety usually occurred together in ECH and CCH patients. CH patients who were depressed or anxious were more likely to present at a younger age and have attack-related nausea and prodromal symptoms. Depressed CH patients were also more likely to have another pain disorder and had undertaken twice as many prophylactic medication trials. CONCLUSION: In this clinic-based cross-sectional study, ECH and CCH patients had similarly low rates of depression and anxiety. Rates were lower than those reported for both episodic and chronic migraine. PMID- 22077837 TI - TSH-secreting pituitary carcinoma with intrathecal drop metastases. PMID- 22077838 TI - The role of marital sexual abstinence in determining fertility: A study of the Yoruba in Nigeria. AB - Summary Although sexual abstinence has probably been the single most important factor in restricting human fertility, Western researchers have tended to regard it as a phenomenon mostly found outside marriage. The research reported here was carried out amongst the Yoruba, a sub Saharan people, among whom it is more desirable in terms of social stability to practise female sexual abstinence mainly within marriage, rather than outside it. A similar situation is found widely in tropical Africa. Data are reported from five surveys carried out in 1973-75 in the Changing African Family and Nigerian Family Projects. Three types of marital abstinence are shown to have an effect in reducing fertility: post natal abstinence (often wrongly described as a 'taboo'), terminal abstinence, and abstinence at other times. Female sexual abstinence is not paralleled by an equal practice of male abstinence, and the main reason for abstinence is to preserve long birth intervals and periods of lactation in a society prone to high rates of infant malnutrition and mortality. It is shown that the Index of Proportions Married (I ( m )) is only one of a number of fertility-weighted indices which can be employed to sub-divide the female reproductive span, and that a complete series of indices adding to unity can be constructed. The duration of lactation and abstinence are found to be related but, because abstinence is traditionally of longer duration, lactation amenorrhoea is of little importance in containing fertility. Married women spend less than half their reproductive lives in periods when sexual relations are possible and marital abstinence is between three and four times more important than delayed marriage in restricting fertility. The period of abstinence is shown to be changing and it is probable that it has never been of an agreed length; the concept of 'natural fertility' is examined in this light. The partial substitution of contraception for the abstinence period is analysed, and the possible effect on fertility considered. PMID- 22077839 TI - Family limitation and the fertility transition: Evidence from the age patterns of fertility in Europe and Asia. AB - Summary The age patterns of marital fertility levels and decline in modern Asia and historical Europe are analysed in order to answer two questions: (1) How closely do the age patterns of marital fertility in both areas prior to a systematic fertility decline conform to the age pattern of natural fertility? (2) How similar are the age patterns of the fertility transition experienced in Europe in the past, and the age pattern of fertility decline now under way in a number of Asian populations? The answers have important implications for our understanding of the fertility transition. They suggest that modern family limitation (i.e. parity-specific fertility control) was largely absent prior to a secular decline in marital fertility in both Europe and Asia. Furthermore, the evidence indicates that once the practice of family limitation starts to spread among the broader strata of the population, it seems almost inevitably to increase until it becomes a common behavioural norm. In this respect, the modern fertility transition appears to result from the spread of innovative behaviour and cannot be viewed simply as an adjustment to new socio-economic circumstances based on previously established behavioural mechanisms. PMID- 22077840 TI - Family limitation among the Old Order Amish. AB - Summary This paper shows that the Indiana Amish, a high-fertility Anabaptist population, regulate their marital fertility according to their family finances. We linked demographic data from the Indiana Amish Directory with personal property tax records at 5, 15 and 25 years after marriage and found fertility differences by occupation and wealth. Correlations between family size and wealth at the beginning, middle and end of childbearing years were positive. Wealthier women exhibited higher marital fertility, had longer first birth intervals, were older at the birth of their last child, and had larger families than poorer women. Over the past 30 years, marital fertility has remained constant among older women; but birth rates among younger women have been rising rapidly. PMID- 22077841 TI - Further developments in indirect mortality estimation. AB - Summary A variety of indirect estimators of mortality; survival of children by marriage duration of mother, survival of first spouse by marriage duration and by age, maternal orphanhood, and survival of siblings, are investigated by the use of a wide range of model fertility and mortality situations. Survival probabilities are then related by regression analysis to the proportions with a particular characteristic, to yield an equation which can then be used to estimate the survival probability in a population. Maternal orphanhood and survival of first spouse by age have already shown themselves to be useful, and the new developments are only simplifications of the existing methodology. Survival of first spouse by duration of marriage, and survival of siblings are, however, new methods which have yet to be justified by field experience. In conclusion, the features common to all indirect mortality estimation procedures are outlined, and the direction future developments may take in response to gradually improving data quality is suggested. PMID- 22077842 TI - Problems in using birth-history analysis to estimate trends in fertility. AB - Summary The problem investigated is the adequacy of birth-history analysis as a method for estimating fertility change. The analysis demonstrates that inaccurate reporting of the dates of birth of live-born children can, under reasonable assumptions, significantly distort cohort fertility schedules in such a way that estimates of change in fertility will be biased in the direction of exaggerating declines in fertility. This kind of bias is shown to exist in fertility estimates obtained from survey data in El Salvador and Bangladesh. An important implication is that birth history questionnaires should begin with the most recent, rather than the earliest, event in a respondent's experience. PMID- 22077843 TI - Religious differentials in fertility: Lebanon, 1971. AB - Summary The principal objects of this study are the description and explanation of the effects of religious affiliation on fertility in the multi-religious society of Lebanon. The data are derived from the 1971 National Fertility and Family Planning Survey which is the first probability sample ever taken of Lebanese couples with wives aged 15-49 years. The present inquiry yields two major results. First, significant fertility differences do exist among Muslims and among Christians. To speak of Muslim-Christian fertility differences is, therefore, misleading. Secondly, religious fertility differentials, based on cumulative fertility, are dependent on the level of wife's education. At low levels of wife's education, differentials are great; at high levels, religious differentials in fertility are insignificant. These findings are believed to be of importance not only to researchers concerned with religious fertility differentials, but also to those concerned with framing population policies in countries where religious composition is a sensitive matter. PMID- 22077844 TI - Decomposing the re-marriage process. AB - Summary For those who experience marital disruption because of discord, the re marriage process consists of a series of steps including divorce and re-marriage. This paper analyses the overall differentials in re-marriage, decomposing them into two distinct parts: differentials in propensity to divorce following separation and re-marriage given that a divorce has occurred. The results indicate that differentials in re-marriage depend in important ways on both steps in the process. PMID- 22077847 TI - Toward a final common pathway of depression: an editorial comment to Jarnum H, Eskildsen SF, Steffensen EG et al. 'Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in depressed patients' (1). PMID- 22077848 TI - The heterogeneity of depression: an old debate renewed. PMID- 22077849 TI - A new era in secondary prevention after acute coronary syndrome. PMID- 22077850 TI - The development of children's regret and relief. AB - Previous research found that children first experience regret at 5 years and relief at 7. In two experiments, we explored three possibilities for this lag: (1) relief genuinely develops later than regret; (2) tests of relief have previously been artefactually difficult; or (3) evidence for regret resulted from false positives. In Experiment 1 (N=162 4- to 7-year-olds) children chose one of two cards that led to winning or losing tokens. Children rated their happiness then saw a better (regret) or worse (relief) alternative. Children re-rated their happiness. Regret after winning was first experienced at 4, regret after losing and relief after winning were experienced at 5 years and relief after losing at 7 years. Experiment 2 (N=297 5- to 8-year-olds) used a similar task but manipulated children's responsibility for the outcome. Greater responsibility for the outcome resulted in a greater likelihood of an experience of regret and relief. Results support that previous tests of relief were artefactually difficult and regret and relief are experienced earlier than previously thought. PMID- 22077851 TI - Wheat germ: not only a by-product. AB - The wheat germ (embryonic axis and scutellum) represents about 2.5-3.8% of total seed weight and is an important by-product of the flour milling industry. The germ contains about 10-15% lipids, 26-35% proteins, 17% sugars, 1.5-4.5% fibre and 4% minerals, as well as significant quantities of bioactive compounds such as tocopherols [300-740 mg/kg dry matter (DM)], phytosterols (24-50 mg/kg), policosanols (10 mg/kg), carotenoids (4-38 mg/kg), thiamin (15-23 mg/kg) and riboflavin (6-10 mg/kg). Oil recovery is achieved by mechanical pressing or solvent extraction, which retrieve about 50% or 90% lipids, respectively; innovative approaches, such as supercritical carbon dioxide extraction, are also proposed. The oil is rich in triglycerides (57% of total lipids), mainly linoleic (18:2), palmitic (16:0) and oleic (18:1) acids, but relevant amounts of sterols, mono- and diglycerides, phospho- and glycolipids are present. The lypophilic antioxidants tocopherols and carotenoids are also abundant. The main by-product of oil extraction is defatted germ meal, which has high protein content (30-32%), is rich in albumin (34.5% of total protein) and globulin (15.6%), and thus presents a well-balanced amino acid profile. Its principal mineral constituents are potassium, magnesium, calcium, zinc and manganese, in decreasing order. Total flavonoid content is about 0.35 g rutin equivalent/100 g DM. The wheat germ is therefore a unique source of concentrated nutrients, highly valued as food supplement. While the oil is widely appreciated for its pharmaceutical and nutritional value, the defatted germ meal is a promising source of high-quality vegetable proteins. Better nutrient separation from the kernel and improved fractioning techniques could also provide high-purity molecules with positive health benefits. PMID- 22077852 TI - Quality-of-care framework in urological cancers: where do we stand? AB - What's known on the subject? and What does the study add? Provision of high quality care necessitates the identification and measurement of relevant quality indicators. Urological surgery currently does not have a validated quality-of care framework to guide surgical quality improvement. This article aims to delineate quality of care processes, current status of quality indicators for major urological cancers as well as recommend a provisional framework for evaluation of quality for urological procedures. Growing demands for patient safety, lower cost and quality of care have resulted in several initiatives of quality measurement across urological surgery. Although candidate indicators have been proposed in various procedures, the field still lacks a valid quality framework. Better understanding of the interplay between patient selection, surgical expertise, preoperative-, intraoperative, postoperative processes and outcomes is needed. Consensus needs to be achieved in which validated structural, process and outcomes measures to employ, how this data should be collected, which agencies to share this data with and how to use this data to effect change in health policy. Compliance with quality framework needs to be continuously audited with its outcomes frequently benchmarked against international standards. Pursuit of quality improvement schemes require significant investment and need to be weighed against current budgetary constraints. PMID- 22077853 TI - Bacterial meningitis among children under the age of 2 years in a high human immunodeficiency virus prevalence area after Haemophilus influenzae type b vaccine introduction. AB - AIM: The aim of this study was to describe bacterial causes of meningitis among children < 2 years in a high human immunodeficiency virus (HIV) prevalence area after introduction of routine Haemophilus influenzae type b vaccination. METHODS: Data collected between April 2003 and December 2008 were extracted from a surveillance database and medical records of children < 2 years admitted in Mbarara Hospital, Uganda with suspected bacterial meningitis. HIV infection was confirmed using rapid tests and polymerase chain reaction and bacterial meningitis by using cerebrospinal fluid culture. RESULTS: Between April 2003 and December 2008, 1464 children under 5 years were admitted with suspected bacterial meningitis of which 1235 (84.4%) had cerebrospinal fluid collected; 894 (72.4%) of these samples were from children < 2 years. Of the 894 samples, 64 (7.2%) grew an organism including Streptococcus pneumoniae (26; 41%), Salmonella species (20; 31%), H. influenzae (6; 9%) and coliforms (7; 11%), and five (8%) grew contaminants that are all coagulase negative Staphylococcus. Of the 894 children, 468 (52.3%) were tested for HIV; 16.7% were positive. Fifty-one children had a pathogenic isolate and a treatment outcome, and 23 (45%) died; 13 (56.6%) deaths were due to S. pneumoniae, eight (34.8%) were due to Salmonella spp., one (4.3%) was due to H. influenzae and one (4.3%) was due to coliforms. HIV infection was associated with a threefold increase in mortality, increased likelihood of a bacterial isolate and decreased likelihood of malaria parasitaemia. CONCLUSION: Following H. influenzae type b vaccine introduction, S. pneumoniae and Salmonella spp. are the major causes of bacterial meningitis among children < 2 years in Uganda. Pneumococcal conjugate vaccines and reduction in mother to child transmission of HIV could reduce the observed mortality. PMID- 22077816 TI - Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. AB - BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.). PMID- 22077854 TI - Nerve supply of the proximal sesamoid bone in the horse. AB - Summary In chronical proximal sesamoid bone lameness it is difficult to localise the exact site of pain. A specific diagnostic analgesia is not available because of a deficiency of detailed information about the nerve supply to the proximal sesamoid bones and surrounding area. A macroscopic study of the nerve distribution to the proximal sesamoid bones of 10 foals and 5 adult horses revealed that these bones are innervated by two branches, in this study called the medial and lateral sesamoidean nerve, respectively, originating from the medial and lateral palmar nerve. Histology of the left forelimbs of two fetuses and one foal confirmed the macroscopic findings. Additionally, histology of ten proximal sesamoid bones of adult horses showed that myelinated nerve fibres are present in the nutrient foramina and in the trabecular bone, accompanying the larger arteries. This study provides possibilities for future diagnostics of proximal sesamoid bone lameness by specific local perineural analgesia. PMID- 22077855 TI - Clinical and force plate evaluation of the effect of a high plantar nerve block in lameness caused by induced mid-metatarsal tendinitis. AB - Summary To answer the question whether it is possible to differentiate, by means of a high plantar nerve block in the hind limb, flexor tendon lameness from a suspensory ligament lameness, mid-plantar tendinitis or desmitis was induced with collagenase in five Standardbred horses in two trials. Before the induction of lameness, and on the fourth (D4) and fourteenth day (D14) after the induction of lameness the horses were evaluated subjectively (clinical lameness score), objectively (ground reaction force (GRF) measurements), and ultrasonographically. Clinical evaluation and GRF measurements were also done on D4 and D14 after a high plantar nerve block. From the GRF measurements variables were selected and analysed and related to the clinical lameness score. The horses were significantly lame on D4; this lameness had decreased on D14. The clinical findings were supported by the GRF data. In the flexor tendon group, a high plantar nerve block resulted in soundness or lameness in the other hind limb, whereas in the suspensory ligament group the effect was less conclusive. The correlation between the subjective clinical lameness score and several objectively measured GRF variables proved to be moderate to high. The collagenase model proved to be useful to study the effect of a high plantar nerve block on lameness resulting from induced tendon/ligament lesion. However, a high plantar nerve block cannot be used to differentiate between flexor tendon and suspensory ligament lesions. PMID- 22077856 TI - Ultrasonographic evaluation and long term follow-up of flexor tendonitis/desmitis in the metacarpal/metatarsal region in Dutch warmblood horses and standardbred racehorses. AB - Summary Over a 2 year-period, the ultrasonographic localization and distribution of flexor tendinous and ligamentous injuries, the long-term follow up, and the outcome were studied in 101 Dutch Warmblood horses (DW) with a mean age of 8.7 years and in 71 Standardbred racehorses (ST) with a mean age of 5.2 years. The ratio between forelimb and hind limb flexor tendonitis/desmitis in the DW-group was 4:1 and in the ST-group 4:3. In the DW-group, tendonitis/desmitis of the suspensory ligament (32%), the superficial digital flexor tendon (29%), the distal carpal check ligament (17%) of the forelimb (SLf, SDFf, and CL, respectively) and the suspensory ligament (11%) of the hind limb (SLh) occurred the most often. In the ST-group, tendonitis of the SDFf (34%) and desmitis of the SLh (34%) and SLf (18%) were the most common injuries. Of the 60 Dutch Warmblood horses available for follow-up, 25% showed full-functional recovery. Of the 61 Standardbreds available for follow-up, 18% showed full functional recovery. Overall, local axial lesions seemed to have a worse prognosis than local abaxial or diffusive lesions. PMID- 22077857 TI - The effect of toe weights on linear and temporal stride characteristics of standardbred trotters. AB - Summary Toe weights are applied to influence the stride characteristics of trotters. The quantitative effect of 88-g toe weights on the stride characteristics of Standardbred trotters was evaluated in a kinematic study using a CODA-3 analysis system. Six trotters were studied at a speed of 11 m/s on a treadmill. Temporal gait variables, joint angles, and the trajectories of the forelimb hoof were calculated. The stride patterns of the individual trotters were assessed by a judge and compared to the CODA-output. Those trotters with poor flexion of the carpal joint during the swing phase or with insufficient knee action responded with better carpal flexion and more knee action when toe weights were attached. No effect of toe weights on the protraction of the forelimb could be demonstrated. Stride length, stride duration, and the relative duration of the stance and swing phase as a percentage of the stride did not respond to toe weights. It is concluded that toe weights can be useful in Standardbred trotters, but their effect depends on the individual gait pattern. PMID- 22077858 TI - Accessory carpal bone fractures in the horse. AB - Summary The clinical signs, the radiographic appearance, and the treatment of two cases of fracture of the accessory carpal bone are described. The fractures were in the vertical plane. Surgical intervention consisted out of fixation of the fracture with two lag screws. Follow-up information revealed that one horse became sound and returned to complete athletic activity whereas the other horse remained lame. A brief literature review is given and the surgical treatment and the complications are discussed. PMID- 22077859 TI - Cancellous bone grafting in the treatment of bovine septic physitis. AB - Summary Eleven young cattle (8-24 months of age) were treated for septic physitis of the metacarpal or metatarsal bones. Two new elements were added to the traditional treatment. Firstly, homologous cancellous bone grafts were used for their osteoinductive properties even in an infected surrounding. (Actinomyces pyogenes was recovered most commonly.) Secondly, a walking cast was applied for better immobilization of the lower limb with minimal discomfort to the animal. After surgery, the 11 bovine patients needed an average walking cast period of 4.5 weeks and 1 to 2 weeks' treatment with antibiotics. The new treatment regime expedites the healing process and shows a success rate of 100%. Follow-up after 6 months revealed that all animals were completely sound without recurrence of the physitis. PMID- 22077860 TI - A modified technique for implantation of polypropylene mesh for the repair of external abdominal hernias in horses: A review of 21 cases. AB - Summary During a 3-year period 21 horses were surgically treated because of large abdominal wall defects. In each case the defect was bridged with a polypropylene mesh, which was placed on the outside of the hernial ring. This was in contrast with the technique for mesh herniorrhaphy generally described in human and veterinary literature, in which the mesh is always implanted on the inside of the hernial ring. One horse was destroyed on the first postoperative day because of postanaesthetic myelomalacia. Surgical repair as described was successful in 18 patients. Recurrence of herniation occurred in two horses. On re herniorrhaphy a second and larger mesh was successfully implanted. PMID- 22077861 TI - Single intraoperative administration of antibiotic to cows with caecal torsion: Wound infection and postoperative performance. A retrospective and prospective study. AB - Summary Wound infection and postoperative performance after a single intra abdominal administration of 9 g sodium ampicillin in cows operated on for caecal dilatation or torsion (n=33) were evaluated. In the 25 animals that left the clinic in good health (76% short-term survival), no wound infection occurred. Postoperative performance was normal in 21 of these animals (84%). The figures for short-term survival and postoperative performance are comparable to those from a retrospective study of 169 animals operated on between 1985 and 1990. Single intra- abdominal administration of sodium ampicillin during surgery provides good protection against infection without negative effects on the postoperative performance. PMID- 22077862 TI - Oral bioavailability of pivampicillin in foals at different ages. AB - Summary The plasma disposition of ampicillin after intravenous administration at a dose rate of 15 mg/kg was studied in six healthy, 1-month-old foals. The oral bioavailability of pivampicillin was determined in the same foals at four ages, ranging from 11 days to 4 months. Pivampicillin was administered orally at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 12 hours after administration. After intravenous administration, the mean distribution and elimination half-lives of ampicillin were 0.121 and 0.624 h, respectively. The volume of distribution (Vss) appeared to be 0.334 1/kg. Orally administered pivampicillin was rapidly absorbed in all age groups, producing mean peak plasma concentrations of 3.83 to 5.69 MUg/ml 1 h after administration. The mean bioavailability of pivampicillin in the different age groups ranged from 39.4 to 52.9 %. There was no statistically significant difference in peak plasma concentration or bioavailability between the age groups. It is concluded that pivampicillin at a dose rate of 19.9 mg/kg orally gives satisfactory plasma concentrations in foals of all ages. PMID- 22077863 TI - Laboratory and clinical evaluation of a chromogenic endotoxin assay for horses with acute intestinal disorders. AB - Summary In this study the laboratory and clinical performance of a chromogenic endotoxin assay for equine plasma was evaluated. The assay was sensitive (detection limit 3 ng LPS/L plasma), reproducible (within and between-assay CV at 50 ng LPS/L E.coli 0111:B4 LPS standard addition was 5% and 7.5%, respectively), and not substantially affected by enhancement or inhibition phenomena (recovery of an in vitro spike was 75-125% in 80% of the samples). LPS added to whole blood was rapidly inactivated upon incubation at 37 degrees C but not at 0 degrees C. A recently developed blood collection tube for LPS testing was found suitable, i.e. LPS-free and providing non-contaminated samples. In 48 horses suffering from acute abdominal diseases requiring surgical treatment, LPS levels were significantly higher in platelet-rich plasma (PRP) than in platelet-poor plasma (PPP), and the proportional difference was related to the PRP platelet count (r=0.52, p<0.001, mean difference 48%, range 8-77%). LPS levels were also significantly higher in horses that died or were euthanized than in surviving horses (mean 16.5 and 7.1 ng/L PRP, respectively, p<0.05). We conclude that LPS can be measured in equine plasma with picogram sensitivity and recommend the use of PRP instead of PPP for clinical LPS testing. For clinical use a decision limit for endotoxaemia of 5 ng LPS/L PRP appeared to be inadequate. Analysis at a higher cut-off level for endotoxaemia and the evaluation of clinical, pathological, and laboratory parameters would be more meaningful. PMID- 22077864 TI - Intravenous anaesthesia in horses by guaiphenesinketamine-detomidine infusion: Some effects. AB - Summary The effects of total intravenous anaesthesia with an intravenous infusion of a combination of guaiphenesin, ketamine and detomidine were studied in 10 patients scheduled for elective surgery. Anaesthesia was maintained by the infusion of guaiphenesin (100 mg/ml), ketamine (2 mg/ml) and detomidine (0.02 mg/ml). The infusion rate was 1 ml/kg/hr. During anaesthesia, pulse rate and mean arterial blood pressure were continuously recorded. Arterial blood gases and pH were determined immediately after induction and at stated times during anaesthesia. Venous blood was sampled to determine plasma glucose, lactate, lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate aminotransferase (AST) concentrations. Values were compared with those determined in blood sampled before the premedication. All determined parameters with the exception of the plasma glucose concentration, the arterial oxygen tension and the AST concentration did not change significantly and remained within normal ranges. The plasma glucose concentration increased significantly after the induction of anaesthesia compared to the control value but decreased to normal values during anaesthesia. The arterial oxygen tension was on average 30% lower than normally wished. Compared to the control value the plasma concentration of AST was significantly decreased at the end of anaesthesia. Based upon the results of this study an infusion of guaiphenesin, ketamine and detomidine appears to be useful for the maintenance of total anaesthesia in horses. PMID- 22077866 TI - Increasing the exchange time-scale that can be probed by CPMG relaxation dispersion NMR. AB - Carr-Purcell-Meiboom-Gill relaxation dispersion NMR spectroscopy has emerged as a valuable tool to characterize conformational exchange between major and minor states in a large variety of biomolecules. The window of exchange that is amenable for study, corresponding to rates on the order of 2000 s(-1) or less, is limiting, however. Here we show that a combined analysis of both amide (15)N and (1)H(N) CPMG profiles and major state exchange induced (15)N chemical shift changes leads to significant increases in the exchange time scale for which accurate exchange parameters and chemical shift differences between the interconverting states can be obtained. The utility of the approach is illustrated with examples involving a pair of protein systems that are in the moderately fast exchange regime. In these cases the analysis of dispersion profiles alone is not sufficient to obtain robust measures of exchange parameters and chemical shift differences. Inclusion of major state exchange induced (15)N chemical shift changes measured in ((15)N-(1)H(N)) HMQC and HSQC data sets in addition to the (15)N and (1)H(N) dispersion profiles in the analysis "breaks" the correlation in parameters, allowing accurate values to be obtained. The approach is straightforward to implement and makes use of HMQC/HSQC data sets that are recorded as a matter of routine to obtain chemical shifts of the excited state. It promises to increase the range of exchanging systems involving low populated, transiently formed excited states that can be studied by relaxation dispersion NMR. PMID- 22077867 TI - Osteopontin--a fibrosis-related marker--in dilated cardiomyopathy in patients with Emery-Dreifuss muscular dystrophy. AB - BACKGROUND: As osteopontin (OPN) may be assumed to have diagnostic/prognostic value in heart diseases, it is worth assessing whether it is also involved in the pathogenesis and can be applied in the diagnosis of the dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD). METHODS: Serum levels of osteopontin were quantified by means of sandwich immunoassay in 25 EDMD patients (10 laminopathies AD-EDMD and 15 emerinopathies--X-EDMD), eight carriers of X EDMD, nine disease controls (patients with dystrophinopathy) and 20 age-matched healthy controls. RESULTS: The levels of circulating OPN were elevated in all AD EDMD and X-linked EDMD patients, as well as in X-EDMD carriers and patients suffering progressive muscular dystrophy. There was no correlation between the osteopontin level and different cardiac parameters, including left-ventricular end-diastolic diameter, left atrial diameter, the left ventricular ejection fraction and the CK-MB level. There was a slight negative correlation with the ages of the patients. CONCLUSIONS: The presented results indicate that assessments of circulating OPN levels may help to identify EDMD patients at risk of dilated cardiomyopathy and might be therefore included among the set of biomarkers referred to with a view to appropriate early cardiologic diagnosis and therapy being commenced with in time. PMID- 22077868 TI - Investigation of six selected bacterial species in endo-periodontal lesions. AB - AIM: To investigate and determine possible associations of six tested bacteria belonging to 'orange' and 'green' complexes, in endo-periodontal lesions: Parvimonas micra, Fusobacterium nucleatum, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens and Capnocytophaga sputigena. METHODOLOGY: Forty-six patients presenting with different types of endo-periodontal lesions were investigated. Clinical examinations, periapical radiographs and microbiological sampling from the canal system (endo) and periodontal pockets (perio) were performed. Qualitative and semiquantitative evaluation of bacteria was performed by polymerase chain reaction (PCR) and DNA-DNA hybridization (micro-IDent plus; Hain Lifescience, Germany). RESULTS: Extremely high bacterial loads in endodontic samples were recorded for P. micra, F. nucleatum and C. sputigena, while periodontal samples were often colonized by the same species, plus C. rectus. Significant association was recorded between F. nucleatum-endo and P. micra-endo (P = 0.03, Fisher's exact test). There was marginal evidence of associations between: (i) C. sputigena-endo and C. sputigena-perio (P = 0.06, Fisher's exact test); (ii) P. micra-endo and P. micra-perio (P = 0.05, Fisher's exact test). Sensitivity to percussion was associated with an increased chance of cases with P. micra-endo (P = 0.03, Pearson chi-square test). CONCLUSION: The findings suggest that F. nucleatum, P. micra and C. sputigena may play a role in the pathogenesis of endo-periodontal lesions. PMID- 22077869 TI - Effects of hydrocortisone on acute beta-adrenoceptor blocker and histamine induced bronchoconstriction. AB - AIMS: beta-adrenoceptor blockers are avoided in asthma due to concerns of bronchoconstriction. We investigated the safety of acute exposure to propranolol in asthmatics, sequentially challenged with histamine to mimic an asthma exacerbation and evaluated the role of intravenous hydrocortisone in potentiating salbutamol reversibility. METHODS: Persistent atopic asthmatics, requiring <= 1000 ug day(-1) budesonide, performed a randomized double-blind placebo controlled crossover study. Following 10 mg or 20 mg of oral propranolol, patients received 400 mg intravenous hydrocortisone or placebo, followed by histamine challenge with nebulized salbutamol 5 mg and ipratropium 500 ug recovery. RESULTS: Thirteen patients completed per protocol. Hydrocortisone did not potentiate salbutamol recovery post propranolol and histamine challenge vs. placebo (mean difference in FEV(1) 0.04 ml, 95% CI -0.07, 0.15, P= 0.417). beta adrenoceptor blocker induced bronchoconstriction was demonstrated by spirometry and impulse oscillometry. For the placebo visit, FEV(1) fell 4.7% 2 hours post propranolol (95% CI 1.8, 7.5, P= 0.008) whilst total airway resistance (R5%) increased 31.3% (95% CI 15.6, 47.0, P= 0.04). On both visits FEV(1) % and R5% returned to baseline after salbutamol post histamine. CONCLUSION: Nebulized salbutamol and ipratropium produced a full recovery after propranolol and histamine induced bronchoconstriction, independent of hydrocortisone use. Since the greatest risk of beta-adrenoceptor blockade is after first dose, our findings offer reassurance to those undertaking further evaluation of chronic beta adrenoceptor blockade as a potential treatment for mild-to-moderate asthma. PMID- 22077870 TI - Diversity of human hair pigmentation as studied by chemical analysis of eumelanin and pheomelanin. AB - Hair colour is one of the most conspicuous phenotypes in humans, ranging from black, brown, blond to red. This diversity arises mostly from the quantity and ratio of the black-dark brown eumelanin and the reddish-brown pheomelanin. To study the chemical basis underlying the diversity of hair colour, we have developed several chemical methods to quantify those two pigments. Alkaline H(2) O(2) oxidation affords pyrrole-2,3,5-tricarboxylic acid (PTCA) as a eumelanin marker and thiazole-2,4,5-tricarboxylic acid (TTCA) as a pheomelanin marker. Pheomelanin can also be analysed as 4-amino-3-hydroxyphenylalanine (4-AHP) after hydroiodic acid hydrolysis. Using those methods, we evaluated the contents of eumelanin and pheomelanin (the 'chemical' phenotype) in human hairs of black, dark brown, brown, light brown, blond and red colour (the 'visual' phenotype). Eumelanin contents decrease in that order, with a trace but constant level of pheomelanin, except for red hair which contains about equal levels of pheomelanin and eumelanin. Thus, the chemical phenotype correlates well with the visual phenotype. The genotype of melanocortin-1 receptor (MC1R), a gene regulating the red hair phenotype, is predictive of hair melanin expressed as the log value of eumelanin to pheomelanin ratio, with a dosage effect evident. Hair melanin contents were also analysed in patients with various hypopigmentary disorders including Hermansky-Pudlak syndrome, Menkes disease, proopiomelanocortin deficiency, cystinosis, malnutrition and trace metal deficiency. The chemical phenotype helped evaluate the precise effects of each disease on pigmentation. In studies of human hair, the chemical phenotype will find more and more application as an objective measure of pigmentation. PMID- 22077871 TI - Localized Wegener's granulomatosis. AB - BACKGROUND: Wegener's granulomatosis (WG) is a rare granulomatous necrotizing vasculitis of small and medium vessels which has predilection for upper airways, lungs and kidney. However, any other organ, including the skin and oral cavity, can be involved. Although mucocutaneous lesions are relatively common, they have only rarely been reported as localized manifestation of the disease. OBJECTIVES: Our aim was to evaluate the type and sites of skin and mucosal lesions, clinical course and response to treatment, histologic features and laboratory findings in localized WG. METHODS: The medical records of three patients (two women and one man) with localized WG followed up at our hospitals for a mean time of 10 years were studied. RESULTS: All patients presented with facial plaques infiltrating the nasal and palatal mucosae and cartilages and, in one case, perforating the palatal bone. Anti-neutrophil cytoplasmic antibodies, which are the marker for multisystem WG, were negative. The disease, refractory to various immunosuppressants, responded well, albeit incompletely, to prednisone plus cyclophosphamide. LIMITATIONS: The limited number of patients is counterbalanced by the rarity of the disease. CONCLUSIONS: Our cases may represent a rare distinctive subset of WG limited to the facial region and upper airway mucosa but showing a locally aggressive behaviour leading to cartilage and bony destruction. PMID- 22077872 TI - Usefulness of the script concordance test in dermatology. AB - BACKGROUND: The script concordance test (SCT) measures clinical data interpretation in the context of uncertainty. To our knowledge, its feasibility has not yet been demonstrated in dermatology. OBJECTIVES: This study describes the feasibility, reliability and validity of the SCT for use in dermatology teaching to family medicine residents. METHODS: We designed an SCT for dermatology teaching, adapted to the level of family medicine students. The family medicine residents attending a dermatology lecture course and a reference panel of dermatologists underwent the test. Software available on the SCT dedicated website was used to determine the scores. The Cronbach's alpha was calculated. The scores were described by means, standard deviation, and minimum and maximum scores. Mann-Whitney tests were used to compare resident and reference panel scores. RESULTS: The test contained 33 vignettes of four questions each. Cronbach's alpha was 0.80. Mean scores were 75.6 for the reference panel and 65.0 for the residents (P = 0.0009). CONCLUSIONS: This study confirmed the SCT's capacity to distinguish groups on the basis of experience. This study demonstrated the feasibility and reliability of the SCT in the field of dermatology. PMID- 22077874 TI - The role of cholesterol in UV light B-induced apoptosis. AB - Modification of major lipid raft components, such as cholesterol and ceramide, plays a role in regulation of programmed cell death under various stimuli. However, the relationship between cholesterol level modification and the activation of apoptotic signaling cascades upon UVB light has not been established. In this report, we demonstrate that upon UVB irradiation cholesterol levels in membrane rafts of skin cells increase, which leads to Fas-receptor (Fas) aggregation in the rafts. Utilizing a continuous velocity floatation technique, we show that Fas accumulated in the lipid rafts of human melanoma M624 cells after UVB irradiation. The subsequent events of death-inducing signaling complex formation were also detected in the lipid raft fractions. Depletion of cholesterol by methyl-beta-cyclodextrin reduces Fas aggregation, while overloading increases. Disruption of lipid rafts also prevents Fas death domain associated protein (Daxx) from dissociating from Fas in the lipid rafts, which is accompanied with a reduced apoptotic, but increased nonapoptotic death of UVB irradiated human keratinocytes, HaCaT cells. Results indicate that cholesterol located in the plasma membrane of skin cells is required for lipid raft domain formation and activation of UVB-induced apoptosis. PMID- 22077875 TI - Isolation and biological characterization of non-B HIV type 1 from Kenya. AB - The isolation and characterization of primary strains of human immunodeficiency virus (HIV) is a vital tool for assessing properties of viruses replicating in HIV-infected subjects. HIV-1 isolation was carried out from 30 HIV-1-infected patients from a Comprehensive Care Clinic (CCC) after informed consent. Virus was successfully isolated from 9 out of the 30 samples investigated. Seven of the isolates were from drug-naive patients while two were from patients on antiretroviral drugs. The isolates were biologically phenotyped through measurement of the syncytium-inducing capacity in MT2 cells. Six of the isolates exhibited syncytia induction (SI) associated with CXCR4 coreceptor usage while three of the isolates were non-syncytia-inducing (NSI) isolates associated with CCR5 coreceptor usage. In addition, the replication capacity of the isolates was further determined in established cell line CD4(+) C8166. Indirect immunofluorescence assay was used to check the antigen expression on the cells as a supplementary test. HIV-1 isolation success was 70% (7/10) and 20% (2/20) in naive and drug-experienced patients, respectively. The majority of the viral isolates obtained (6/9) were of the SI phenotype, though SI virus strains are rare among non-B subtypes. A significant correlation between virus isolation success and viral load was established. Coreceptor use data for heavily treatment experienced patients with limited treatment options are scanty and this is the group with perhaps the most urgent need of novel antiretroviral agents. PMID- 22077876 TI - Molecular docking and competitive binding study discovered different binding modes of microsomal prostaglandin E synthase-1 inhibitors. AB - Microsomal prostaglandin E synthase-1 (mPGES-1) is a newly recognized therapeutic target for the treatment of inflammation, pain, cancer, atherosclerosis, and stroke. Many mPGES-1 inhibitors have been discovered. However, as the structure of the binding site is not well-characterized, none of these inhibitors was designed based on the mPGES-1 structure, and their inhibition mechanism remains to be fully disclosed. Recently, we built a new structural model of mPGES-1 which was well supported by experimental data. Based on this model, molecular docking and competition experiments were used to investigate the binding modes of four representive mPGES-1 inhibitors. As the inhibitor binding sites predicted by docking overlapped with both the substrate and the cofactor binding sites, mPGES 1 inhibitors might act as dual-site inhibitors. This inhibitory mechanism was further verified by inhibitor-cofactor and inhibitor-substrate competition experiments. To investigate the potency-binding site relationships of mPGES-1 inhibitors, we also carried out molecular docking studies for another series of compounds. The docking results correlated well with the different inhibitory effects observed experimentally. Our data revealed that mPGES-1 inhibitors could bind to the substrate and the cofactor binding sites simultaneously, and this dual-site binding mode improved their potency. Future rational design and optimization of mPGES-1 inhibitors can be carried out based on this binding mechanism. PMID- 22077877 TI - Selective transition state stabilization via hyperconjugative and conjugative assistance: stereoelectronic concept for copper-free click chemistry. AB - Dissection of stereoelectronic effects in the transition states (TSs) for noncatalyzed azide-alkyne cycloadditions suggests two approaches to selective transition state stabilization in this reaction. First, the formation of both 1,4 and 1,5-isomers is facilitated via hyperconjugative assistance to alkyne bending and C...N bond formation provided by antiperiplanar sigma-acceptors at the propargylic carbons. In addition, the 1,5-TS can be stabilized via attractive C H...F interactions. Although the two effects cannot stabilize the same transition state for the cycloaddition to alpha,alpha-difluorocyclooctyne (DIFO), they can act in a complementary, rather than competing, fashion in acyclic alkynes where B3LYP calculations predict up to ~1 million-fold rate increase relative to 2 butyne. This analysis of stereoelectronic effects is complemented by the distortion analysis, which provides another clear evidence of selective TS stabilization. Changes in electrostatic potential along the reaction path revealed that azide polarization may create unfavorable electrostatic interactions (i.e., for the 1,5-regioisomer formation from 1-fluoro-2-butyne and methyl azide). This observation suggests that more reactive azides can be designed via manipulation of charge distribution in the azide moiety. Combination of these effects with the other activation strategies should lead to the rational design of robust acyclic and cyclic alkyne reagents for fast and tunable "click chemistry". Further computational and experimental studies confirmed the generality of the above accelerating effects and compared them with the conjugative TS stabilization by pi-acceptors. PMID- 22077879 TI - Comment on "do some NOx emissions have negative environmental damages? Evidence and implications for policy". PMID- 22077880 TI - The lived experiences of parents of children diagnosed with cancer in Iran. AB - Threatening nature of childhood cancer and the aggressiveness of prescribed treatments place enormous stress on the family of children suffering from cancer. This study was conducted to better understand the lived experiences of parents of children suffering from cancer and to document their account of such experiences. The aim of this research was to describe the lived experiences of parents of children diagnosed with cancer in Iran. This hermeneutic phenomenological study was conducted between June 2008 and May 2009. Data were generated from 15 parents using in-depth interviews to capture their experiences of having children with cancer. Analysis is based on the framework of Diekelmann enabled data interpretation and elaboration of shared themes. One constitutive pattern 'Feeling trapped in the cancer dead end' and four related themes, namely 'Contradiction in reconciliation with situation', 'Doomed to accept', 'Isolation from others' and 'Devastated life', were identified. The results of this study showed that parents feel as if they are trapped by their child's disease. They are affected by several mental, social and familial issues while trying to tolerate their child's illness and conform to the new order of life. PMID- 22077881 TI - Myocardial performance index derived from preejection period: a novel and feasible parameter in evaluation of cardiac performance in patients with permanent atrial fibrillation. AB - BACKGROUND: Using tissue Doppler echocardiography, we can measure preejection period (PEPa), defined as the interval measured from the onset of QRS to the onset of the systolic mitral annular velocity pattern, isovolumic relaxation time (IVRTa), defined as the interval measured from the end of systolic mitral annular velocity pattern to the onset of diastolic mitral annular velocity pattern, and ejection time (ETa), defined as the interval measured from the onset to the end of systolic mitral annular velocity pattern on the same cardiac cycle. The aim of this study is to test the applicability of PEPa-derived myocardial performance index (MPI), defined as the ratio of PEPa + IVRTa to ETa, as an indicator of combined left ventricular systolic and diastolic function in patients with permanent atrial fibrillation. METHODS: Echocardiographic examination was performed in 54 consecutive patients with permanent atrial fibrillation. Clinical and echocardiographic parameters were compared and analyzed. RESULTS: After a multivariate analysis, the average RR interval on the tissue Doppler image (beta= 0.328, P = 0.002), left ventricular ejection fraction (beta=-0.260, P = 0.024), and early diastolic mitral annular velocity (beta=-0.408, P < 0.001) were the major determinants of PEPa-derived MPI. CONCLUSIONS: PEPa-derived MPI had a significant correlation with echocardiographic left ventricular diastolic and systolic function. It may be a novel and feasible indicator in assessment of global left ventricular function in patients with permanent atrial fibrillation. PMID- 22077883 TI - Mitral valve regurgitation in patients supported on continuous flow pumps. PMID- 22077884 TI - The mixing mechanism during lithiation of Si negative electrode in Li-ion batteries: an ab initio molecular dynamics study. AB - In order to realize Si as a negative electrode material in commercial Li-ion batteries, it is important to understand the mixing mechanism of Li and Si, and stress evolution during lithiation in Si negative electrode of Li-ion batteries. Available experiments mainly provide the diffusivity of Li in Si as an averaged property, neglecting information regarding diffusivity of Si. However, if Si can diffuse as fast as Li, the stress generated during Li diffusion can be reduced. We, therefore, studied the diffusivity of Li as well as Si atoms in the Si-anode of Li-ion battery using an ab initio molecular dynamics-based methodology. The electrochemical insertion of Li into crystalline Si prompts a crystalline-to amorphous phase transition. We considered this situation and thus examined the diffusion kinetics of Li and Si atoms in both crystalline and amorphous Si. We find that Li diffuses faster in amorphous Si as compared to crystalline Si, while Si remains relatively immobile in both cases and generates stresses during lithiation. To further understand the mixing mechanism and to relate the structure with electrochemical mixing, we analyzed the evolution of the structure during lithiation and studied the mechanism of breaking of Si-Si network by Li. We find that Li atoms break the Si rings and chains and create ephemeral structures such as stars and boomerangs, which eventually transform to Si-Si dumbbells and isolated Si atoms in the LiSi phase. Our results are found to be in agreement with the available experimental data and provide insights into the mixing mechanism of Li and Si in Si negative electrode of Li-ion batteries. PMID- 22077885 TI - Cu(I)- and proton-binding properties of the first N-terminal soluble domain of Bacillus subtilis CopA. AB - CopA, a P-type ATPase transporter involved in copper detoxification in Bacillus subtilis, contains two soluble Atx1-like domains separated by a short linker at its N-terminus, an arrangement that occurs widely in copper transporters from both prokaryotes and eukaryotes. Both domains were previously found to bind Cu(I) with very high affinity. Above a level of 1 Cu(I) per CopAab, dimerization occurred, leading to a highly luminescent multinuclear Cu(I) species [Singleton C & Le Brun NE (2009) Dalton Trans, 688-696]. To try to understand the contributions of each domain to the complex Cu(I)-binding behaviour of this and related proteins, we purified a wild-type form of the first domain (CopAa). In isolation, the domain bound Cu(I) with very high affinity (K = ~ 1 * 10(18) m(-1) ) and underwent Cu(I)-mediated protein association, resulting in a mixture of dimer and tetramer species. Addition of further Cu(I) up to 1 Cu(I) per CopAa monomer led to a weakly luminescent species, whereas further additions [2 Cu(I) per CopAa monomer] resulted in protein unfolding. Analysis of the MTCAAC binding motif Cys residue acid-base properties revealed pK(a) values of 5.7 and 7.3, consistent with the pH dependence of Cu(I) binding, and with the proposal that low proton affinity is associated with high Cu(I) affinity. Finally, Cu(I) exchange between CopAa and the chelator bathocuproine sulfonate revealed rapid exchange in both directions, demonstrating an interaction between the protein and the chelator that catalyses metal ion transfer. Overall, CopAa exhibits similarities to CopAab in terms of affinity and complexity of Cu(I) binding, but the details of Cu(I) binding are distinct. PMID- 22077887 TI - Headache among patients with HIV disease: prevalence, characteristics, and associations. AB - BACKGROUND: Headache is one of the most common medical complaints reported by individuals suffering from human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), but limited and conflicting data exist regarding their prevalence, prototypical characteristics, and relationship to HIV disease variables in the current era of highly active antiretroviral therapy (HAART). OBJECTIVES: The aims of the present cross-sectional study were to characterize headache symptoms among patients with HIV/AIDS and to assess relations between headache and HIV/AIDS disease variables. METHODS: Two hundred HIV/AIDS patients (49% female; mean age = 43.22 +/- 12.30 years; 74% African American) from an internal medicine clinic and an AIDS outreach clinic were administered a structured headache diagnostic interview to assess headache characteristics and features consistent with International Classification of Headache Disorders (ICHD)-II diagnostic semiologies. They also completed 2 measures of headache related disability. Prescribed medications, most recent cluster of differentiation (CD4) cell count, date of HIV diagnosis, possible causes of secondary headache, and other relevant medical history were obtained via review of patient medical records. RESULTS: One hundred seven patients (53.5%) reported headache symptoms, the large majority of which were consistent with characteristics of primary headache disorders after excluding 4 cases attributable to secondary causes. Among those who met criteria for a primary headache disorder, 88 (85.44%) met criteria for migraine, most of which fulfilled ICHD-II appendix diagnostic criteria for chronic migraine. Fifteen patients (14.56%) met criteria for episodic or chronic tension-type headache. Severity of HIV (as indicated by CD4 cell counts), but not duration of HIV or number of prescribed antiretroviral medications, was strongly associated with headache severity, frequency, and disability and also distinguished migraine from TTH. CONCLUSIONS: Problematic headache is highly prevalent among patients with HIV/AIDS, most of which conform to the semiology of chronic migraine, although with some atypical features such as bilateral location and pressing/tightening quality. A low frequency of identifiable secondary causes is likely attributable to reduced frequency of opportunistic infections in the current era of HAART. Disease severity is strongly predictive of headache, highlighting the importance of physician attention to headache symptoms and of patient adherence to treatment. PMID- 22077889 TI - David victor glass (1911-1978). PMID- 22077888 TI - Association of prostate cancer risk alleles with unfavourable pathological characteristics in potential candidates for active surveillance. AB - OBJECTIVE: * To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance. PATIENTS AND METHODS: * We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate specific antigen <10 ng/mL, biopsy Gleason <=6, three or fewer positive cores, <=50% tumour involvement/core) but instead underwent early radical prostatectomy. * We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason >=7 and/or >= pT2b in their radical prostatectomy specimen. RESULTS: * In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have 'unfavourable' pathological characteristics. * The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. * Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. * Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). * Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen. CONCLUSION: * In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen. PMID- 22077890 TI - The Decline of marital fertility in Japan. AB - Summary Studies concerning the demographic history of Tokuwara and Meiji Japan suggest that fertility rose substantially before declining during the twentieth century. Were the motivations and circumstances which held down natality during the feudal period similar to those which account for the modern fertility decline and the low birth rate obtaining in the Japan of to-day? The thesis of this paper is that the pre-modern situation was fundamentally different from the modern one. During the Tokugawa era infanticide and abortion were used, independently of parity, to eliminate weak offspring whose chances of survival were deemed poor. Desired natality generally exceeded natural fertility. With the rise of income per head during the Meiji period the population's need for these desparate practices vanished. To-day parity-specific control characterizes fertility. Parityspecific control was diffused throughout Japan in response to declining desired fertility. Desired fertility fell significantly below natural fertility sometime during the late nineteenth or early twentieth century and the wish to reduce actual fertility to the desired level stimulated the adoption of parity specific control. The speed of decline in marital fertility was partially governed by official policies toward contraception and abortion, contraception and abortion. PMID- 22077891 TI - The Relevance of the 'Easterlin hypothesis' and the 'new home economics' to fertility movements in Great Britain. AB - Summary The hypothesis that a family's economic status relative to its aspirations (relative economic status) is an important determinant of its fertility behaviour has been developed and applied to the explanation of swings in American fertility by R. A. Easterlin. However, a recent application by Butz and Ward of a model derived from the 'new home economics' (pioneered by Becker and Mincer) strongly suggests that relative economic status is not the dominant factor in explaining fertility movements in the U.S.A. Rather, both current men's and women's wages operate independently in explaining the movement in fertility, and in particular the decline in fertility is attributed to rising women's wages. In this paper we explore the relevance of both the Easterlin hypothesis and the hypotheses derived from the 'new home economics' to the 1955-75 fertility swing in Great Britain. We find that we must reject the Easterlin hypothesis on the basis of the measures of relative economic status suggested by Easterlin and Wachter. A variant of the Easterlin hypothesis suggested by Oppenheimer does receive some support from the available evidence, and the evidence provides strong support for the model of fertility behaviour derived from the 'new home economics', which emphasizes the distinction between the effects of changes in men's and women's real wages on fertility decisions. The cause of the fertility decline is attributed to rising women's wages and employment opportunities through their direct effect on the opportunity cost of time and children among working wives and through their effect on the labour force participation of married women of childbearing age. The test of this model and the estimates of its parameters are not definitive, however, because of deficiencies in the data and problems of statistical estimation. We nevertheless conclude that both this model and the Oppenheimer variant of the Easterlin hypothesis, as well as other elements of a more comprehensive economic theory of fertility, point to a continuation of low fertility and the possibility of a secular decline with fertility approaching some lower asymptote. PMID- 22077892 TI - Models of contemporary Dutch family building. AB - Summary Recent data suggest that the level of use of oral contraceptives in the Netherlands is perhaps the highest in the world. Moreover, the greatest recent change in family building patterns is the tendency of newly weds to postpone their first birth. A micro-simulation model was developed to test the effect on fertility of such a change. An attempt was made to employ input data compatible with conditions obtaining in the Netherlands, and the distributions of family building patterns were based on recent survey evidence. The aim was not to duplicate Dutch fertility, but rather to estimate the range over which marital duration-specific fertility can be expected to vary with an increase in the proportion of couples who space their first birth. Such an increase was found to lower fertility dramatically after five years of marriage, although completed fertility was seen to vary very little. This result indicates the care that must be taken in ascribing a decline in the fertility of the early years of marriage to an overall fertility decline. PMID- 22077893 TI - The four-parameter logit life table system. AB - Summary Brass's model life table system, which is a two parameter system based on the logit transformation of survivorship values, has been widely and successfully used to describe age patterns of mortality in many populations. As more reliable information has become available for populations with mortality patterns which differ in important ways from the assumed standard pattern of mortality, a more flexible model system is needed. This paper shows how Brass's system can be expanded into a four-parameter model, and evaluates the performance of the new system by examining how well it can fit observed life table data. PMID- 22077894 TI - Fertility and mortality in Finland since 1750. AB - Summary In this paper the development of fertility and mortality in Finland, and their interrelations with each other and with economic factors is discussed. An analysis by individual years shows that rises and falls in mortality and fertility rates did not always coincide with poor and good harvests. Fertility in Finland decreased slightly at the turn of the eighteenth and nineteenth centuries, but fell sharply over the period 1876-1925. This fall corresponded closely to changes in the death rate, especially for infants, and appears to justify the conclusion that the changes were connected. These population shifts have been called the first and second demographic transitions, of which the latter was the more dramatic. Factors tending to reduce mortality among infants and in other age groups during the second demographic transition are obvious; those underlying the first demographic transition are less clear. In this connection, the importance of breast feeding and campaigns designed to favour the practice are stressed. These helped to reduce infant mortality and were one of the main reasons for the first demographic transition. Finnish material also suggests that some kind of family planning existed during the pre-industrial period; it is only by making this assumption that the various figures can be made compatible. PMID- 22077895 TI - Emigration from Canada in the 1960s. AB - Summary Emigration from Canada can be assessed only by indirect means. Here, survival ratios have been applied to the total population enumerated in the 1961 Census and to particular segments of it, so that a comparison of the calculated numbers in 1971 with the population actually enumerated indicates the volume of emigration during the decade, both in the whole population and in certain groups. Amounting to two-thirds of the number of immigrants during the same period, the estimate for the ten years is exactly double the volume of emigration reported to the Joint Parliamentary Committee on immigration policy of 1975. Since 1971, the level of emigration has probably fallen. Of the 960,000 emigrants during the decade, 42 per cent were Canadian-born. Their favourite destination was the United States; immigrants, on the other hand, tended to return home. Many immigrants now stay in Canada for only a few years. Fewer Canadians emigrate to the United States. These two factors have contributed to a new pattern of emigration, up-to-date details of which will not be ascertained before the Census of 1981. PMID- 22077896 TI - The population policy of China. AB - Summary China has a consistent and well-defined policy to regulate the growth of her population. Population policy is considered as an integral part of overall social and economic development policy. It promotes the reduction of the growth rate in densely populated areas but encourages the increase of population in sparsely populated areas and among national minorities. A series of planned internal migration policies has regulated the spatial distribution of population. Main factors affecting the implementation of China's population policy are the establishment of an effective organization and communication system, the participation of the masses in the work, the socialist transformation of the national economy, the changes in the structure and functions of the Chinese family, the changing status of Chinese women, the development of public health services and the campaign for late marriage and family planning. PMID- 22077897 TI - Cholera epidemics and their control in Ceylon. AB - Summary Although cholera was never endemic in Ceylon, the country was subject to frequent (and in many instances explosive) cholera epidemics, due to its many contacts with the Indian sub-continent, the source where the disease was endemic. The frequency of epidemics was caused by the heavy movement of Indian labour working on the plantations of Ceylon between the two countries. This study charts the course of cholera in Ceylon beginning in the nineteenth century and seeks to identify the causes which led to its decline. Although there has always been doubt regarding the efficacy of quarantine in controlling cholera, its history in Ceylon indicates that whatever the drawbacks, quarantine was one of the major factors leading to the decline of this disease in the country. In addition, one of the essential elements in the battle against cholera in Ceylon was the development of a public health department which had the capacity to restrict the spread of an epidemic. This was done by the timely enforcement of various public health measures when the disease escaped the quarantine net. This survey also indicates that in the case of Ceylon, medical treatment and hospitalization was of no significance in controlling the number of deaths among those who contracted cholera, since all the great cholera epidemics occurred before treatment by intravenous re-hydration was introduced. PMID- 22077898 TI - The differential attainment of family size goals by Race. AB - Summary The 1973 U.S. National Survey of Family Growth is used to examine the effects of removing number and timing failures from the reproductive histories of various cohorts of white and black married women. Blacks are more fertile than whites primarily because of their greater unwanted fertility. Removing number and timing failures from the past reproductive histories of American women would have reduced their fertility considerably. These reductions would have been greater for blacks than for whites and would be greater if some wanted pregnancies had continued to terminate in foetal loss. PMID- 22077899 TI - A method for deriving mortality estimates from incomplete vital Statistics. AB - Summary Although they are available in many developing countries vital registration records are very little used for mortality estimation which is still mainly based on census returns. However, defective death records may yield accurate estimations of mortality. This procedure requires few data only; a sex age distribution of the population (preferably at the middle of a period) and a sexage distribution of deaths, either derived from vital records or from census returns to questions relating to deaths during the preceding twelve months. This method is based on the observation that for a fixed age structure of the population, there is a one-one relation between the age structure of deaths (measured by the proportion of deaths at older ages) and the level of mortality (measured by the death rate above a certain minimum age). It is assumed that at ages above this minimum the rate of underregistration of deaths does not vary significantly with age. Therefore, the age distribution of registered deaths makes it possible to estimate the true proportion of deaths at older ages. This in its turn will permit the estimation of the true level of mortality, because of the relation which exists between age structure of deaths and level of mortality. The true level is then compared with the observed, to estimate the rate of underregistration, and observed age-specific death rates can be adjusted in the light of this knowledge. PMID- 22077900 TI - A study of the correlation bias of unrecorded events by two independent enumeration systems. AB - Summary In this paper the allegation that, when using the Chandrasekar-Deming technique with two independent enumeration systems to record the incidence of vital events and migrations, each individual system misses the same type of event is investigated. If this correlation bias were to occur frequently enough, it could result in a serious underestimation of a given type of event. Using vital events and migrations data derived from a longitudinal survey conducted in Liberia between 1969 and 1973, the estimated number of recorded events is tabulated into homogeneous groups that are demonstrated to affect omission rates. The proportion of missed eyents is computed separately for each enumeration system, and the presence or absence of a significant correlation mathematically determined. The results of this study suggest that no significant correlation could be demonstrated in the type of birth, death or infant death that was commonly missed by each individual enumeration system. This indicates that the omission of a birth, death or infant death was apparently a random occurrence as far as the individual casefinding systems were concerned. The authors conclude that any underestimation of vital events from this type of correlation bias may not be as serious as originally imagined. In contrast to this observation, the omission of particular types of migrations by each enumeration system was apparently not a random occurrence, but was associated with the direction of migration. This implies that selected migration rates in the liberian survey were probably understated and this could happen in other longitudinal surveys, unless specific precautions are taken to avoid it. PMID- 22077903 TI - Ustekinumab in clinical practice: response depends on dose and previous treatment. AB - OBJECTIVES: To evaluate the efficacy of ustekinumab in a series of patients with moderate to severe psoriasis treated according to the European Medicines Agency (EMA) label and to identify factors such as dose, baseline PASI or previous treatment potentially related to therapeutic outcome. METHODS: Retrospective review of the clinical records from 36 consecutive patients treated with ustekinumab during at least 36 weeks at a single referral center. Candidates for treatment had a PASI>=10 or a BSA>=10 and either failure to respond to, or a contraindication to, or intolerance to some systemic or another biologic treatment. The main outcome measures were PASI improvement with respect to baseline at weeks 12 and 24 (prior to the third injection of ustekinumab). RESULTS: Overall 75%, 69%, and 86% patients achieved PASI75 response rates at weeks 12, 24 and 36, respectively. Patients weighing<=100 kg and treated with 45 mg doses had better PASI 50, PASI75 and PASI90 response rates than heavier patients (treated with 90 mg) at every point in time, and the differences were statistically significant at week 24. PASI75 response rates at week 24 were significantly better in patients with no prior exposure to TNFalpha blocking agents (85% vs. 50%, P=0.0235). CONCLUSIONS: In clinical practice, ustekinumab is effective both in biologic-nayve patients and as salvage therapy when other biological treatments have failed. The response rates prior to the third injection in our series were better in patients weighing<=100 kg and in those without previous exposure to biologics. PMID- 22077905 TI - Increasing diversity of Human Immunodeficiency Virus type 1 subtypes circulating in Australia. AB - Characterization of HIV subtypes can provide a more comprehensive understanding of the epidemic within a distinct region, and when combined with notification data, may also be helpful in enhancing current HIV prevention strategies. In this study, we characterized 1056 HIV-positive individuals (948 males and 108 females) living in Victoria and whose infection was detected for the first time between 2005 and 2010 inclusive. HIV-1 strains were subtyped based on pol gene sequence. Phylogenetic analysis was performed on all non-B subtype sequences identified. Of the 1056 sequences analyzed, 825 were subtype B and 231 were non-B. Overall 6 HIV 1 subtypes, 6 circulating recombinant forms (CRFs), and 12 unique recombinant forms (URFs) were identified. Regardless of gender, the majority of individuals were infected with a subtype B virus (78%). Subtype B was dominant in males (n=806, 85%). In contrast, the majority of females were infected with non-B subtypes (n=89, 82%), in particular subtype C (n=48, 45%). Phylogenetic analysis of the non-B subtypes revealed that the majority of clustering, and thereby transmission, occurred with CRF01_AE strains. Despite the relatively high numbers identified in females there was very little clustering of subtype C viruses. Subtypes C and A1 both historically associated with heterosexual transmission, and CRF01_AE often associated with IVDU, were also associated with transmission within the MSM population, demonstrating the potential for non-B subtypes to expand into the MSM population. The observation of increasing numbers of females and heterosexual males infected with non-subtype B viruses, the majority imported through migration and travel to countries where there is a high prevalence of HIV, suggests a targeted public health message may be required to prevent further increases within these two groups. PMID- 22077904 TI - Miconazole induces fungistasis and increases killing of Candida albicans subjected to photodynamic therapy. AB - Cutaneous and mucocutaneous Candida infections are considered to be important targets for antimicrobial photodynamic therapy (PDT). Clinical application of antimicrobial PDT will require strategies that enhance microbial killing while minimizing damage to host tissue. Increasing the sensitivity of infectious agents to PDT will help achieve this goal. Our previous studies demonstrated that raising the level of oxidative stress in Candida by interfering with fungal respiration increased the efficiency of PDT. Therefore, we sought to identify compounds in clinical use that would augment the oxidative stress caused by PDT by contributing to reactive oxygen species (ROS) formation themselves. Based on the ability of the antifungal miconazole to induce ROS in Candida, we tested several azole antifungals for their ability to augment PDT in vitro. Although miconazole and ketoconazole both stimulated ROS production in Candida albicans, only miconazole enhanced the killing of C. albicans and induced prolonged fungistasis in organisms that survived PDT using the porphyrin TMP-1363 and the phenothiazine methylene blue as photosensitizers. The data suggest that miconazole could be used to increase the efficacy of PDT against C. albicans, and its mechanism of action is likely to be multifactorial. PMID- 22077906 TI - Early family context and development of adolescent ruminative style: moderation by temperament. AB - We know very little about the development of rumination, the tendency to passively brood about negative feelings. Because rumination is a risk factor for many forms of psychopathology, especially depression, such knowledge could prove important for preventing negative mental health outcomes in youth. This study examined developmental origins of rumination in a longitudinal sample (N=337; 51% girls) studied in preschool (ages 31/2 and 41/2 years) and early adolescence (ages 13 and 15 years). Results indicated that family context and child temperament, assessed during the preschool period, were risk factors for a ruminative style in adolescence. Specifically, early family contexts characterised by over-controlling parenting and a family style of negative submissive expressivity predicted higher levels of later rumination. These associations were moderated by children's temperamental characteristics of negative affect and effortful control. Further, the interaction of these temperament factors exerted an additional influence on later rumination. Implications for prevention and intervention efforts are discussed. PMID- 22077907 TI - A randomised controlled trial of the efficacy of supported employment. AB - OBJECTIVE: Although numerous randomised controlled trials indicated the superiority of supported employment (SE), we still have too little evidence that SE is more effective than traditional vocational rehabilitation programmes (TVR) in Western European countries with highly developed social security and welfare systems, sophisticated rehabilitation programmes and high thresholds to the open labour market. The aim of this study is to prove the efficacy of SE in Switzerland. METHOD: Following a 2-week intake assessment, 100 unemployed persons with stabilised severe mental illness (SMI) were randomly assigned to either the SE programme (n=46) or to the most viable locally available TVR (n=54). Follow-up lasted 24 months. RESULTS: After the first year, the rate of competitive employment reached a mean level of 48.2% in the SE group and of 18.5% in the TVR group. 58.7% of the SE group were ever competitively employed as opposed to 25.9% of the TVR group. In the second year, SE group participants were competitively employed for 24.5 weeks as compared with 10.2 in the TVR group. The groups showed no significant differences in the non-vocational outcome criteria. CONCLUSION: The SE programme in Switzerland also proved more effective than TVR and seems to be applicable to the socio-economic context of Western European countries. PMID- 22077908 TI - "Lighthouse in the dark": a qualitative study of the role of breast care nurse specialists in Israel. AB - This study gains insight into the role of the breast care nurse specialist through an analysis of thank you letters written by women with breast cancer in a tertiary hospital in Israel. Descriptive content analysis was used to analyze 125 thank you letters. The findings revealed three aspects of the role of the breast care nurse specialist: instrumental, cognitive, and emotional. The women described these aspects as "paving the way through bureaucracy" (instrumental), being a "traffic light at a crossroad in life" (cognitive), and treating each one of them "as if I am your only patient" (emotional). This analysis highlighted the significance of the breast care nurse specialist in a holistic and integrative role that fills a gap within the biomedical healthcare system. Transferability of the findings to other nurse specialist roles in different clinical settings should be investigated. PMID- 22077910 TI - Editorial. PMID- 22077909 TI - Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. AB - BACKGROUND: The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population. METHODS: Immediately before PCI, we randomly assigned, in a double blind manner, 1721 patients with acute non-ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days. RESULTS: The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval [CI], 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02). CONCLUSIONS: Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non-ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451.). PMID- 22077911 TI - Cross-cultural adaptation and psychometric properties of the Brazilian-Portuguese version of the Duke Anticoagulation Satisfaction Scale. AB - AIM: The aim of this study was to evaluate the internal reliability and validity of the Brazilian-Portuguese version of Duke Anticoagulation Satisfaction Scale (DASS) among cardiovascular patients. BACKGROUND: Oral anticoagulation is widely used to prevent and treat thromboembolic events in several conditions, especially in cardiovascular diseases; however, this therapy can induce dissatisfaction and reduce the quality of life. DESIGN: Methodological and cross-sectional research design. METHODS: The cultural adaptation of the DASS included the translation and back-translation, discussions with healthcare professionals and patients to ensure conceptual equivalence, semantic evaluation and instrument pretest. The Brazilian-Portuguese version of the DASS was tested among subjects followed in a university hospital anticoagulation outpatient clinic. The psychometric properties were assessed by construct validity (convergent, known groups and dimensionality) and internal consistency/reliability (Cronbach's alpha). RESULTS: A total of 180 subjects under oral anticoagulation formed the baseline validation population. DASS total score and SF-36 domain correlations were moderate for General health (r=-0.47, p<0.01), Vitality (r=-0.44, p<0.01) and Mental health (r=-0.42, p<0.01) (convergent). Age and length on oral anticoagulation therapy (in years) were weakly correlated with total DASS score and most of the subscales, except Limitation (r=-0.375, p<0.01) (Known groups). The Cronbach's alpha coefficient was 0.79 for the total scale, and it ranged from 0.76 (hassles and burdens)-0.46 (psychological impact) among the domains, confirming the internal consistency reliability. CONCLUSIONS: The Brazilian-Portuguese version of the DASS has shown levels of reliability and validity comparable with the original English version. RELEVANCE TO CLINICAL PRACTICE: Healthcare practitioners and researchers need internationally validated measurement tools to compare outcomes of interventions in clinical management and research tools in oral anticoagulation therapy. PMID- 22077913 TI - Could head circumference be used to screen for autism in young males with developmental delay? AB - AIM: Research has suggested an abnormal acceleration in head circumference growth in children with autism within the first 12 months of life. This study aimed to examine head circumference at birth and head circumference growth rates in young children with autism and developmental delay, and young children with developmental delay without autism. METHODS: This study assessed head circumference at birth and rate of change in head circumference in young children with autism (n=86) and children with developmental delay without autism (n=40). RESULTS: For both groups of children, head circumference at birth and head circumference growth were compared with Centers for Disease Control normative data. No differences were found between the group of children with autism and developmental delay compared with the group with developmental delay only. However, when the sample was compared with a range of selected Centers for Disease Control normative medians, the children with autism were found to have significantly smaller head circumferences at birth and significantly larger head circumference at 18.5 months of age. CONCLUSIONS: These results are discussed in relation to the potential of accelerated head circumference growth as an early marker for autism. This study failed to find a difference in the head circumferences of children with autism and developmental delay and children with developmental delay only, thus suggesting that head circumference measurement has limited value as an early marker for autism. PMID- 22077912 TI - The behavioral activation system and mania. AB - For over two decades, theorists have suggested that mania relates to heightened sensitivity of the behavioral activation system (BAS). In this article, we review a burgeoning empirical literature on this model, drawing on both cross-sectional and prospective studies. As evidence has emerged for this model, we argue that it is time to consider more specific aspects of BAS sensitivity in this disorder. We review evidence that bipolar disorder relates to an increased willingness to expend effort toward reward and to increases in energy and goal pursuit after an initial reward. We conclude by considering the strengths and weaknesses of this literature, with an eye toward future directions and implications for treatment. PMID- 22077914 TI - Low- vs. high-pressure suction drainage after total knee arthroplasty: a double blind randomized controlled trial. AB - AIM: The aim of this study was to assess the efficacy of continuous low-pressure suction drainage compared with closed high-pressure suction following total knee arthroplasty. BACKGROUND: Closed wound drainage systems are used in surgical interventions to reduce the incidence of haematomas, promote wound healing and reduce infections. However, evidence shows that using a closed wound drainage system can increase transfusion requirements. DATA SOURCES: A randomized, double blind and parallel controlled trial was performed. Adult knee replacement patients recruited between May 2006 and March 2007 were assigned to receive low pressure suction of 50 mmHg (experimental drainage) or high-pressure suction of 700 mmHg (comparator drainage). METHODS: The primary outcome was total blood loss after surgery. Secondary outcomes were incidence of transfusion, complications and mortality. Statistical analysis was based on an intention-to-treat approach. Linear regression was performed to account for factors that could influence blood loss. RESULTS: A total of 169 patients were included. Mean age was 73 (+/-6) years, 128 women and 41 men. A total of 84 patients were randomized to the experimental drainage and 85 to the comparator drainage. Analysis showed a total postoperative blood loss of 541.8 mL in the experimental group and 524.4 mL in the comparator group (P = 0.734). The only factor that showed an association with blood loss was the length of surgery. Linear regression did not show differences between the groups. CONCLUSION: Continuous low-pressure suction of 50 mmHg is not more effective than the higher aspiration pressure system to diminish the blood loss in total knee arthroplasty. The results do not support any change in current nursing practice relating to the use of this drain system. PMID- 22077915 TI - Effectiveness of calcium hydroxide-based intracanal medicaments against Enterococcus faecalis. AB - AIM: To evaluate the antimicrobial efficacy of calcium hydroxide-based intracanal medicaments against Enterococcus faecalis. METHODOLOGY: One hundred and six single-rooted human teeth were inoculated with E. faecalis (ATCC 29212) and incubated in an microaerophilic environment for 21 days. Teeth were divided according to the medicaments and period: G1 - Calen (7 days); G2 - Calen (14 days); G3 - Calen/camphorated paramonochlorophenol (CMCP) (7 days); G4 - Calen/CMCP (14 days); G5 - Calen/0.4% chlorhexidine (CHX) (7 days); G6 - Calen/0.4% CHX (14 days); G7 - Calen/1% CHX (7 days); G8 - Calen/1% CHX (14 days); G9 - chemo-mechanical preparation with no medication and G10 - no chemo mechanical preparation and no medication. Microbial samples were harvested immediately after removal of the intracanal dressing and 7 days later. Data were subjected to anova (P < 0.05). RESULTS: All medicaments were associated with a reduction in E. faecalis after removal of the dressing (post-medication harvest). However, all specimens were associated with an increase in CFU mL(-1) values after 7 days (final harvest). Calen/CMCP and Calen/CHX had the lowest CFU mL(-1) values (P < 0.05). CONCLUSION: In this laboratory study using extracted teeth all calcium hydroxide-based medicaments were able to significantly reduce the CFU mL( 1) values of E. faecalis in the root canal system. PMID- 22077916 TI - Discovery of alpha7-nicotinic receptor ligands by virtual screening of the chemical universe database GDB-13. AB - The chemical universe database GDB-13 enumerates 977 million organic molecules up to 13 atoms of C, N, O, Cl, and S that are virtually possible following simple rules for chemical stability and synthetic feasibility. Analogs of nicotine were identified in GDB-13 using the city-block distance in MQN-space (CBD(MQN)) as a similarity measure, combined with a restriction eliminating problematic structural elements. The search was carried out with a Web browser available at www.gdb.unibe.ch . This virtual screening procedure selected 31 504 analogs of nicotine from GDB-13, from which 48 were known nicotinic ligands reported in Chembl. An additional 60 virtual screening hits were purchased and tested for modulation of the acetylcholine signal at the human alpha7 nAChR expressed in Xenopus oocytes, which led to the identification of three previously unknown inhibitors. These experiments demonstrate for the first time the use of GDB-13 for ligand discovery. PMID- 22077917 TI - Coronary artery fistula: 64-slice computed tomographic delineation and correlation with multiplane transesophageal echocardiography and surgical findings. AB - A 49-year-old female who presented with 3 weeks of exertional chest pain had an abnormal mediastinal finding at chest x-ray imaging. Conventional, nongated computed tomography of the chest revealed a "mass" in proximity to the right atrium. 64-slice, cardiac gated computed tomographic coronary angiography, and transesophageal echocardiography delineated the "mass" as a coronary artery fistula structure. The fistula originated from the left main as a tubular vessel that continued into an aneurysmal sac-like cavity that emptied into the superior vena cava near the right atrium. Computed tomographic coronary angiography showed otherwise normal coronary arteries. Findings were ultimately confirmed at cardiac catheterization. Coronary steal was clinically diagnosed and she underwent surgical ligation and resection of the fistula and aneurysm. Her subsequent course was uncomplicated. PMID- 22077918 TI - Endocrine Society Congenital Adrenal Hyperplasia Guidelines: great content but how to deliver? PMID- 22077919 TI - Benzobisoxazole cruciforms: heterocyclic fluorophores with spatially separated frontier molecular orbitals. AB - We report the synthesis of nine conjugated cruciform-shaped molecules based on the central benzo[1,2-d:4,5-d']bisoxazole nucleus, at which two conjugated currents intersect at a ~90 degrees angle. Cruciforms' substituents were varied pairwise among the electron-neutral phenyl groups, electron-rich 4-(N,N dimethylamino)phenyl substituents, and electron-poor pyridines. Hybrid density functional theory calculations revealed that the highest occupied molecular orbitals (HOMOs) are localized (24-99%) in all cruciforms, in contrast to the lowest unoccupied molecular orbitals (LUMOs) which are strongly dependent on the substitution and less localized (6-64%). Localization of frontier molecular orbitals (FMOs) along different axes of these cruciforms makes them promising as sensing platforms, since analyte binding to the cruciform should mandate a change in the HOMO-LUMO gap and the resultant optical properties. This prediction was verified using UV/vis absorption and emission spectroscopy: cruciforms' protonation results in hypsochromic and bathochromic shifts consistent with the preferential stabilization of HOMO and LUMO, respectively. In donor-acceptor substituted systems, a two-step optical response to protonation was observed, wherein an initial bathochromic shift is followed by a hypsochromic one with continued acidification. X-ray diffraction studies of three selected cruciforms revealed the expected ~90 degrees angle between the cruciform's substituents, and crystal packing patterns dominated by [pi...pi] stacking and edge-to-face [C H...pi] contacts. PMID- 22077921 TI - Co-administration of haloperidol and drugs affecting the angiotensin pathway: effect on the extrapyramidal system. AB - The present study investigates the extrapyramidal effects of co-administration of enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin receptor blocker) with haloperidol in mice. Enalapril/losartan (as a suspension in 1% gum acacia) was administered by oral gavage and haloperidol was administered as an intraperitoneal injection to all the animals for seven days. Catalepsy was measured 30 min after the administration of haloperidol (1 mg/kg i.p.) on days 1 and 7. Observations on day 1 constituted the acute study (single dose administration) and observations on day 7, constituted the chronic study (repeated dose administration). Both acute and chronic administration of enalapril/losartan produced an increase in the duration of haloperidol induced catalepsy at the highest dose (20 mg/kg). Enalapril produced a more pronounced increase in the duration of catalepsy as compared to losartan on both acute and chronic administration. Results of our study suggest that co-administration of anti-psychotics and drugs affecting the angiotensin system can lead to an increase in motor side effects and therefore should be used with caution in patients with these co-morbid conditions. PMID- 22077920 TI - An immunoassay to evaluate human/environmental exposure to the antimicrobial triclocarban. AB - A sensitive, competitive indirect enzyme-linked immunosorbent assay (ELISA) for the detection of the antimicrobial triclocarban (TCC) was developed. The haptens were synthesized by derivatizing the para position of a phenyl moiety of TCC. The rabbit antisera were screened and the combination of antiserum 1648 and a heterologous competitive hapten containing a piperidine was further characterized. The IC(50) and detection range for TCC in buffer were 0.70 and 0.13-3.60 ng/mL, respectively. The assay was selective for TCC, providing only low cross-reactivity to TCC-related compounds and its major metabolites except for the closely related antimicrobial 3-trifluoromethyl-4,4'-dichlorocarbanilide. A liquid-liquid extraction for sample preparation of human body fluids resulted in an assay that measured low part per billion levels of TCC in small volumes of the samples. The limits of quantification of TCC were 5 ng/mL in blood/serum and 10 ng/mL in urine, respectively. TCC in human urine was largely the N- or N' glucuronide. TCC concentrations of biosolids measured by the ELISA were similar to those determined by LC-MS/MS. This immunoassay can be used as a rapid, inexpensive, and convenient tool to aid researchers monitoring human/environmental exposure to TCC to better understand the health effects. PMID- 22077922 TI - Outcome of HIV-1-associated cryptococcal meningitis, Denmark 1988-2008. AB - INTRODUCTION: The risk of HIV-1-associated Cryptococcus neoformans meningitis (CM) has decreased and the outcome has improved with the use of combination antiretroviral therapy (cART). Outcome has not been reported in Denmark in the cART era. METHODS: A review of all cases of HIV-1-associated CM treated at 2 hospitals in Denmark was carried out. Survival was compared by time-updated Cox proportional hazards analysis. RESULTS: A total of 45 cases were evaluated. Six individuals (13.3%) died within 30 days of being diagnosed with CM. cART was initiated a median of 15 days (range 3-53) after a diagnosis of CM for 12 individuals and did not affect 30-day outcome. Older age, however, was associated with an increased risk of death at 30 days (mortality rate ratio (MMR) 1.16 (95% confidence interval (95% CI) 1.05-1.30) per y increment). Twenty-four (55.8%) of 43 individuals (2 had emigrated) died within the 1(st) y. Initiation of cART significantly improved 1-y outcome (MMR 0.22, 95% CI 0.06-0.77). Mental status, CD4 T cell count, and antifungal did not affect short- or long-term outcome. CONCLUSIONS: We found that long-term survival after HIV-1-associated CM has improved significantly with the use of cART. Short-term mortality was not affected by initiation of cART and remained high. PMID- 22077923 TI - Src family kinases in the nervous system. AB - Src family kinases (SFKs) are key factors in the process of coupling signals from the cell surface to intracellular machinery and critically involved in the regulation of many neural functions mediated through growth factors, G-protein coupled receptors or ligand-gated ion channels. The three minireviews here focus on recent findings dealing with the regulation of N-methyl-d-aspartate (NMDA) receptors by SFKs. PMID- 22077924 TI - Short-lasting unilateral neuralgiform headache with autonomic symptoms syndrome as the initial manifestation of idiopathic hypertrophic cranial pachymeningitis. AB - This is the first report of 2 patients presenting with short-lasting unilateral neuralgiform headache with autonomic symptoms as the initial manifestation of idiopathic hypertrophic cranial pachymeningitis. They both had acute retro orbital pain ipsilateral to the dural thickening on magnetic resonance imaging of brain, and one had transient miosis as an additional parasympathetic feature. Short-lasting unilateral neuralgiform headache with autonomic symptoms syndrome may be associated with secondary central nervous system pathology, and neuroimaging should be considered in all patients with trigeminal autonomic cephalalgia. PMID- 22077925 TI - Carbendazim impends hepatic necrosis when combined with imazalil or cypermethrin. AB - Imazalil, cypermethrin and carbendazim are detected in plants for human nutrition. To explore whether their combinations, applied orally in low doses, would induce changes in metabolic patterns and hepatotoxicity, a subchronic in vivo experiment was conducted. Doses of 10mg/kg of imazalil (im) and cypermethrin (cy) and 20 mg/kg of carbendazim (car) and their combinations (im, 10 mg/kg+cy, 10mg/kg; im, 10mg/kg+car, 20mg/kg; car, 20 mg/kg + im, 10 mg/kg) were given to Swiss mice daily over 28 days. After 24 hr from the last dose, the relationships of cytotoxicity biomarkers were analysed: serum lactate dehydrogenase, aspartate transaminase, alanine transferase, amylase, alkaline phosphatase, creatine kinase, creatinine and total proteins. Individual pesticides showed different toxic potential (cy>im car) generally characterized by increase in enzyme activities. Histological analysis showed that cypermethrin, but not imazalil or carbendazim, alone can cause mild necrosis. Combinations generally caused decrease in the activity of enzymes, indicating liver damage. Low doses of carbendazim in combination with low doses of imazalil or cypermethrin caused very pronounced hepatic necrosis, more than any of the three individually applied pesticides or combination of imazalil and cypermethrin. In fruits and vegetables for human consumption, residues of these three pesticides and prolonged combined intake of low doses, which by themselves acutely would not cause any effect, may have similar hepatotoxic effects. PMID- 22077926 TI - Inter-doctor variations in the assessment of functional incapacities by insurance physicians. AB - BACKGROUND: The aim of this study was to determine the--largely unexplored- extent of systematic variation in the work disability assessment by Dutch insurance physicians (IPs) of employees on long-term sick leave, and to ascertain whether this variation was associated with the individual characteristics and opinions of IPs. METHODS: In March 2008 we conducted a survey among IPs on the basis of the 'Attitude--Social norm--self-Efficacy' (ASE) model. We used the ensuing data to form latent variables for the ASE constructs. We then linked the background variables and the measured constructs for IPs (n = 199) working at regional offices (n = 27) to the work disability assessments of clients (n = 83,755) and their characteristics. These assessments were carried out between July 2003 and April 2008. We performed multilevel regression analysis on three important assessment outcomes: No Sustainable Capacity or Restrictions for Working Hours (binominal), Functional Incapacity Score (scale 0-6) and Maximum Work Disability Class (binominal). We calculated Intra Class Correlations (ICCs) at IP level and office level and explained variances (R2) for the three outcomes. A higher ICC reflects stronger systematic variation. RESULTS: The ICCs at IP level were approximately 6% for No Sustainable Capacity or Restrictions for Working Hours and Maximum Work Disability Class and 12% for Functional Incapacity Score. Background IP variables and the measured ASE constructs for physicians contributed very little to the variation--at most 1%. The ICCs at office level ranged from 0% to around 1%. The R2 was 11% for No Sustainable Capacity or Restrictions for Working Hours, 19% for Functional Incapacity Score and 37% for Maximum Work Disability Class. CONCLUSION: Our study uncovered small to moderate systematic variations in the outcome of disability assessments in the Netherlands. However, the individual characteristics and opinions of insurance physicians have very little impact on these variations. Our findings provided no indications of other reasons for these variations. They may be related to different work routines or to different views on the workload of a 'normal' employee. If so, they could be reduced by well-developed and comprehensively implemented guidelines. Therefore, further research is needed. PMID- 22077928 TI - A pilot study to evaluate the effect of soy isolate protein on the serum lipid profile and other potential cardiovascular risk markers in moderately hypercholesterolemic Chinese adults. AB - This article examines the effect of soy isolate protein on the serum lipids and other potential cardiovascular risk markers in 90 moderately hypercholesterolemic Chinese adults (64 women and 26 men, aged 25 to 70 years). Fasting blood samples were taken before and after consuming 24 g of protein supplied by soy isolate protein supplement (including 18 g soy protein and 6 g milk protein) or milk protein supplement daily for 8 weeks. Dietary intake was assessed by a 3-day record collected at baseline, week 4, and week 8 of the study. The results indicate that the two kinds of protein can modestly improve serum lipids and markers associated with obesity and inflammation. PMID- 22077927 TI - Analysis of genome-wide association study data using the protein knowledge base. AB - BACKGROUND: Genome-wide association studies (GWAS) aim to identify causal variants and genes for complex disease by independently testing a large number of SNP markers for disease association. Although genes have been implicated in these studies, few utilise the multiple-hit model of complex disease to identify causal candidates. A major benefit of multi-locus comparison is that it compensates for some shortcomings of current statistical analyses that test the frequency of each SNP in isolation for the phenotype population versus control. RESULTS: Here we developed and benchmarked several protocols for GWAS data analysis using different in-silico gene prediction and prioritisation methodologies. We adopted a high sensitivity approach to the data, using less conservative statistical SNP associations. Multiple gene search spaces, either of fixed-widths or proximity based, were generated around each SNP marker. We used the candidate disease gene prediction system Gentrepid to identify candidates based on shared biomolecular pathways or domain-based protein homology. Predictions were made either with phenotype-specific known disease genes as input; or without a priori knowledge, by exhaustive comparison of genes in distinct loci. Because Gentrepid uses biomolecular data to find interactions and common features between genes in distinct loci of the search spaces, it takes advantage of the multi-locus aspect of the data. CONCLUSIONS: Results suggest testing multiple SNP-to-gene search spaces compensates for differences in phenotypes, populations and SNP platforms. Surprisingly, domain-based homology information was more informative when benchmarked against gene candidates reported by GWA studies compared to previously determined disease genes, possibly suggesting a larger contribution of gene homologs to complex diseases than Mendelian diseases. PMID- 22077929 TI - Psychosocial variables and obesity-risk-reduction behaviors in Chinese Americans. AB - The objective of this study was to utilize social-psychological theories to explain obesity-risk-reduction behaviors. A questionnaire based on the health belief model and theory of planned behavior was administered to a convenience sample of 300 Chinese Americans in the New York metropolitan area. Psychosocial variables accounted for 40.4% of the variance of obesity-risk-reduction behaviors. Self-efficacy, behavioral intention, and perceived benefits emerged as most influential variables. Forty-eight percent of the variance of behavioral intention was accounted with self-efficacy predominating. Health professionals targeting Chinese Americans need to address self-efficacy, behavioral intention, and perceived benefits of adopting obesity-risk-reduction behaviors. PMID- 22077930 TI - The gathering and consumption of wild edible plants in Nhema communal area, Midlands Province, Zimbabwe. AB - The study documented 67 wild edible plant species belonging to 45 genera and 30 families. Anacardiaceae and Moraceae were the dominant botanical families with 6 species each. Of the reported food plants, 67.7% were fruits, 14.9% vegetables, and the remainder were edible roots, inner bark, seed kernel, juice, and gum. Of edible plants, 79.1% had multiple uses, which included medicinal and construction timber. Only 20.9% of the species were used exclusively for food. Wild edible plants are a significant contributor to the socioeconomic well-being of the local people as they contribute a recognizable source of income especially for women. PMID- 22077931 TI - Nutritional value of 10 traditional dishes of the United Arab Emirates. AB - In the present study, 10 traditional dishes commonly consumed in the United Arab Emirates (U.A.E.) were chemically analyzed for proximate composition and mineral content. In addition, exchange lists for meal planning were developed for those dishes. Significant variations in nutritional value were found among the dishes. Protein content was lowest in chicken harese (3.33%) and highest in maleh (23.57%). The fat content ranged from 1.19% in ragag bread to15.47% in legemat (a sweet dish) while carbohydrate levels ranged from traces in maleh to 76.83% in ragag bread. Significant variations were also observed in major elements and trace elements among the dishes. Data from this study will be useful in calculating nutrient contributions from common traditional dishes in the U.A.E. as well as in planning normal and therapeutic diets. Further studies on the nutritional contributions of other traditional dishes in the U.A.E. are needed. PMID- 22077933 TI - Randomized controlled trial comparing treatment outcome of two compression bandaging systems and standard care without compression in patients with venous leg ulcers. AB - BACKGROUND: In Hong Kong, at the time of the study, compression treatment was not considered usual care for venous leg ulcer patients. AIM: This randomized controlled trial compared quality of life (QOL) aspects in venous leg ulcer patients of over 55-years of age, of short-stretch compression (SSB), four-layer compression bandaging (4LB) and usual care (UC) (moist wound healing dressing, no compression). METHOD: Study period was 24-weeks, the primary outcome was the patient functional status, disease-specific and generic health-related QOL measures and ulcer healing rates, comparing week 1 vs. week 24 (end) results. Assessments included photogrammetry, Brief Pain Inventory, SF-12 Health Survey, Charing Cross Venous Ulcer Questionnaire and Frenchay Activity Index. Data analysis was performed using, where appropriate; Kaplan Meier and log rank chi square and the repeated measures analysis of variance test. RESULTS: A total of 321 patients participated in the study, 45 (14%) withdrew for various reasons. Compression bandaging in both groups significantly reduced pain (P < 0.0001) and improved functional status and QOL. Healing rate at 24 weeks for both compression groups was significant (P < 0.001); for SSB this was 72.0% (77/107) vs. 67.3% in the 4LB group (72/107) and 29.0% (31/107) with usual care. The reduction in ulcer area from weeks 12 to 24 was significant only for SSB (P < 0.047). CONCLUSION: Compression was shown to be feasible for elderly community care patients in Hong Kong and is currently implemented as part of standard venous leg ulcer treatment. PMID- 22077935 TI - Far eastern patterns of Mortality. AB - Summary In this paper a mortality pattern is identified which has not previously been described by model mortality schedules and seems to have occurred only in populations in the Far East. Mortality schedules in Taiwan, Hong Kong, Singapore, and Korea during the past several decades have been characterized by excessively high death rates of men at the older ages. This excess mortality has progressively diminished and most recent death rates for men show only slight deviations from West model life tables. An examination of statistics on causes of death suggests that tuberculosis is at least partly responsible for the excess mortality of men. PMID- 22077934 TI - Cost-effectiveness of Prostate Health Index for prostate cancer detection. AB - OBJECTIVE: * To evaluate the cost-effectiveness of early prostate cancer detection with the Beckman Coulter Prostate Health Index (phi) (not currently available in the USA) adding to the serum prostate-specific antigen (PSA) test compared with the PSA test alone from the US societal perspective. PATIENTS AND METHODS: * Phi was developed as a combination of PSA, free PSA, and a PSA precursor form [-2]proPSA to calculate the probability of prostate cancer and was used as an aid in distinguishing prostate cancer from benign prostatic conditions for men with a borderline PSA test (e.g. PSA 2-10 ng/mL or 4-10 ng/mL) and non suspicious digital rectal examination. * We constructed a Markov model with probabilistic sensitivity analysis to estimate expected costs and utilities of prostate cancer detection and consequent treatment for the annual prostate cancer screening in the male population aged 50-75 years old. * The transition probabilities, health state utilities and prostate cancer treatment costs were derived from the published literature. The diagnostic performance of phi was obtained from a multi-centre study. Diagnostic related costs were obtained from the 2009 Medicare Fee Schedule. * Cost-effectiveness was compared between the strategies of PSA test alone and PSA plus phi under two PSA thresholds (>=2 ng/mL and >=4 ng/mL) to recommend a prostate biopsy. RESULTS: * Over 25 annual screening cycles, the strategy of PSA plus phi dominated the PSA-only strategy using both thresholds of PSA >=2 ng/mL and PSA >=4 ng/mL, and was estimated to save $1199 or $443, with an expected gain of 0.08 or 0.03 quality adjusted life years, respectively. * The probabilities of PSA plus phi being cost effective were approximately 77-70% or 78-71% at a range of $0-$200,000 willingness to pay using PSA thresholds >=2 ng/mL and >=4 ng/mL, respectively. CONCLUSION: * The strategy PSA plus phi may be an important strategy for prostate cancer detection at both thresholds of PSA >=2 ng/mL and PSA >=4 ng/mL to recommend a prostate biopsy compared with using PSA alone. PMID- 22077936 TI - Polygyny and the rate of population growth. AB - Summary The roots, motives and feasibility of practising polygyny in societies with a balanced sex structure and the effect of polygyny on the rate of population growth are considered. High demand for labour combined with limited supply over the last several centuries, had been conducive to the evolution of a polygynous nuptiality pattern. The unprecedentedly high rates of population growth during the last several decades combined with progressive economic development have led to a change in the role of the labour factor and consequently diminished its impact upon polygyny. Polygyny is feasible because of a sex-age differential at first marriage, which enables younger cohorts of women to enter the marriage market, and thus results in a very early age at first marriage and universal incidence of marriage among women. A very young pattern of nuptiality inevitably evolves under polygyny, which tends to raise the rate of population growth. No significant variation in fertility between polygynous and monogamous women was found but substantial gaps in standards of living, child mortality, and educational attainment were noted for polygynous households. The findings imply that during the transition from polygyny to monogamy family size will tend to diminish, although initially fertility may not decline concurrently with changing socio-economic status. The most important effects on the rate of population growth thus result from the increase in age at first marriage and declining proportions of ever married women. PMID- 22077937 TI - Estimating infant mortality trends from child survivorship data. AB - Summary Brass's procedure for estimating mortality from census or survey data on numbers of children born to women by age group and numbers of children surviving is generalized to allow the estimation of mortality trends. The new procedure is applied to data for Costa Rica and peninsular Malaysia. The resulting infant mortality rate estimates are compared with rates calculated from vital registration figures. The comparisons suggest, surprisingly, that the estimates derived from statistics for women aged 30-50 are not noticeably inferior to those derived from those for women aged 20-30. This suggests that the common practice of disregarding statistics for women aged over 30 or 35 years may be a mistake. Figures are presented which suggest that estimates based on women aged less than 20 are likely to be very seriously biased because of differential infant mortality by age of mother at birth. PMID- 22077938 TI - Estimating infant and childhood mortality under conditions of changing mortality. AB - Summary It is well known that estimates of infant mortality obtained using Brass's technique are very accurate. Biases are introduced, however, when one or more of the assumptions on which it relies are violated. Departures from the assumption of constant fertility may be handled by using a variant of the technique which depends on information on the age distribution of surviving children, rather than on indexes of the fertility function. Violations of the assumption of constant mortality - an increasingly common situation in most developing societies - produce upward biases in the estimates. The amount of bias is a function of the speed of mortality decline, the characteristics of the fertility pattern and, finally, of the age of the mother. This paper presents a simple technique which corrects these biases, and in addition, generates estimates of the parameters of the mortality trend. It differs from others in that it uses a cohort definition of mortality decline and relies on knowledge of the age structure of surviving children rather than on indexes of the fertility pattern. PMID- 22077939 TI - The post-partum non-susceptible period: Development and application of model schedules. AB - Summary The duration of the post-partum non-susceptible period is a major determinant of birth intervals in populations with relatively low levels of contraception. Since it depends largely on the length of breast-feeding, it may change rapidly with socio-economic development. Its study is, however, seriously hampered by the limited and defective nature of most data that can be obtained. In the absence of intensive, large-scale prospective studies, sizeable reporting errors and/or sampling fluctuations are almost inevitable. A system of model schedules that summarise the underlying regularities found in empirical schedules is proposed. With a logit transformation, observed schedules of breast-feeding can be related to a standard breast-feeding schedule by just two parameters. Similarly, observed schedules of post-partum amenorrhoea can be related to a standard amenorrhoea schedule. The two systems provide a means of obtaining relatively robust estimates of the duration of lactation or amenorrhoea from partial and flawed data. Several applications of the models for estimation problems, for simulation purposes and for the analysis of the relationships between breast-feeding, amenorrhoea and post-partum abstinence are discussed. PMID- 22077940 TI - Rural-Urban fertility differentials in Southern Nigeria: An assessment of some available evidence. AB - Summary The dearth of information on fertility in Nigeria has hitherto impeded efforts to arrive at a consistent pattern of rural-urban fertility differentials in Nigeria. Attempts were made from the mid-sixties onwards to analyse the pattern of rural-urban fertility differentials in some parts of Southern Nigeria from a few independent sources. One such attempt was made by Olusanya; in his study of Western Nigeria in 1966 and in 1969 he reported a higher urban than rural fertility for that region. This result was supported by Ekanem on the basis of data from his 1972 survey of parts of Eastern Nigeria. Given the relatively wider range of available data presently available for Southern Nigeria, this paper examines the Olusanya - Ekanem data together with recent statistics collected from Western, Mid-Western, and Eastern parts of Nigeria by other workers and points out certain inconsistencies and contradictions in the data and conclusions of Olusanya and Ekanem. It suggests that the bulk of available evidence to date suggests either that there is a trend towards the convergence of rural-urban fertility or a definite pattern of higher fertility in the countryside than in the towns. The conclusion also discusses some technical problems of comparing urban and rural fertility. PMID- 22077943 TI - Multidrug-resistant tuberculosis on Australia's northern border. PMID- 22077944 TI - Management of chronic kidney disease in the elderly. AB - Both chronic kidney disease (CKD) and end-stage renal disease are strongly age related. Although the morbidity and mortality of CKD have significantly improved in recent years because of a greater understanding of its pathophysiology and evidence-based approach to management, the application of this evidence to the elderly CKD patients is often fraught with difficulty. This is because, besides age, the clinical and biological variables that are widely prevalent in the elderly, such as multiple co-morbidities, functional impairments and polypharmacy, and quality of life and functional outcome measures, which are pertinent to this age group, have generally not been incorporated into the available evidence. This paper reviews the current evidence with a view to providing a framework for diagnosing and managing CKD in the elderly. Special references are made to age-related physiological changes in the renal system, assessment of renal function, and management of metabolic complications and end stage renal disease. PMID- 22077945 TI - Prosthetic valve endocarditis: what is the evidence for anticoagulant therapy? AB - The use of anticoagulant therapy in prosthetic valve endocarditis is a controversial management issue. Some authorities believe that anticoagulation increases the potential risk of cerebral haemorrhage after a thromboembolism whereas others, however, affirm that cessation of anticoagulation itself increases the risk of thromboembolism and subsequent morbidity and mortality. We reviewed the association of anticoagulant therapy and cerebral complications in patients with prosthetic valve endocarditis. Our results suggest that anticoagulant therapy reduces the risk of thromboembolism and is not associated with increased risk of intracranial haemorrhage. PMID- 22077946 TI - Right-sided pyriform sinus fistula. PMID- 22077947 TI - Delayed isolated gallbladder rupture after blunt abdominal trauma. PMID- 22077948 TI - Focal hyperperfusion on ictal cerebral perfusion computed tomography in partial seizures mimicking acute stroke. PMID- 22077949 TI - Sodium valproate - a rare cause of eosinophilic pleural effusion. PMID- 22077950 TI - Flow sensing of single cell by graphene transistor in a microfluidic channel. AB - The electronic properties of graphene are strongly influenced by electrostatic forces arising from long-range charge scatterers and by changes in the local dielectric environment. This makes graphene extremely sensitive to the surface charge density of cells interfacing with it. Here, we developed a graphene transistor array integrated with microfluidic flow cytometry for the "flow-catch release" sensing of malaria-infected red blood cells at the single-cell level. Malaria-infected red blood cells induce highly sensitive capacitively coupled changes in the conductivity of graphene. Together with the characteristic conductance dwell times, specific microscopic information about the disease state can be obtained. PMID- 22077951 TI - Integrins and their ligands in rheumatoid arthritis. AB - Integrins play an important role in cell adhesion to the extracellular matrix and other cells. Upon ligand binding, signaling is initiated and several intracellular pathways are activated. This leads to a wide variety of effects, depending on cell type. Integrin activation has been linked to proliferation, secretion of matrix-degrading enzymes, cytokine production, migration, and invasion. Dysregulated integrin expression is often found in malignant disease. Tumors use integrins to evade apoptosis or metastasize, indicating that integrin signaling has to be tightly controlled. During the course of rheumatoid arthritis, the synovial tissue is infiltrated by immune cells that secrete large amounts of cytokines. This pro-inflammatory milieu leads to an upregulation of integrin receptors and their ligands in the synovial tissue. As a consequence, integrin signaling is enhanced, leading to enhanced production of matrix degrading enzymes and cytokines. Furthermore, in analogy to invading tumors, synovial fibroblasts start invading and degrading cartilage, thereby generating extracellular matrix debris that can further activate integrins. PMID- 22077952 TI - In search of causality: a systematic review of the relationship between the built environment and physical activity among adults. AB - BACKGROUND: Empirical evidence suggests that an association between the built environment and physical activity exists. This evidence is mostly derived from cross-sectional studies that do not account for other causal explanations such as neighborhood self-selection. Experimental and quasi-experimental designs can be used to isolate the effect of the built environment on physical activity, but in their absence, statistical techniques that adjust for neighborhood self-selection can be used with cross-sectional data. Previous reviews examining the built environment-physical activity relationship have not differentiated among findings based on study design. To deal with self-selection, we synthesized evidence regarding the relationship between objective measures of the built environment and physical activity by including in our review: 1) cross-sectional studies that adjust for neighborhood self-selection and 2) quasi-experiments. METHOD: In September 2010, we searched for English-language studies on built environments and physical activity from all available years in health, leisure, transportation, social sciences, and geographical databases. Twenty cross sectional and 13 quasi-experimental studies published between 1996 and 2010 were included in the review. RESULTS: Most associations between the built environment and physical activity were in the expected direction or null. Land use mix, connectivity and population density and overall neighborhood design were however, important determinants of physical activity. The built environment was more likely to be associated with transportation walking compared with other types of physical activity including recreational walking. Three studies found an attenuation in associations between built environment characteristics and physical activity after accounting for neighborhood self-selection. CONCLUSION: More quasi-experiments that examine a broader range of environmental attributes in relation to context-specific physical activity and that measure changes in the built environment, neighborhood preferences and their effect on physical activity are needed. PMID- 22077953 TI - Visualization of multipolar longitudinal and transversal surface plasmon modes in nanowire dimers. AB - We study the transversal and longitudinal localized surface plasmon resonances in single nanowires and nanowire dimers excited by the fast traveling electron beam in a transmission electron microscope equipped with high-resolution electron energy-loss spectroscopy. Bright and dark longitudinal modes up to the fifth order are resolved on individual metallic nanowires. On nanowire dimers, mode splitting into bonding and antibonding is measured up to the third order for several dimers with various aspect ratio and controlled gap size. We observe that the electric field maxima of the bonding modes are shifted toward the gap, while the electric field maxima of the antibonding modes are shifted toward the dimer ends. Finally, we observe that the transversal mode is not detected in the region of the dimer gap and decays away from the rod more rapidly than the longitudinal modes. PMID- 22077954 TI - Exploring leadership in community nursing teams. AB - AIMS: This article is a report on a study investigating how leadership is perceived in community nursing teams and how these perceptions are translated into working practices of team leaders. BACKGROUND: The consensus in community nursing literature is that leadership is important, and especially so in a time of change. However, little empirical evidence exists on how leadership works in practice. METHOD: The study adopted an exploratory descriptive design, utilising individual semi-structured interviews and focus groups in four case-studies, with a total of 54 participants. Two case-studies focussed on district nursing teams and two involved public health nursing teams, located in two geographical areas. Participants debated their understanding of the concept of leadership, its associated practices and behaviours in teams, if they saw themselves as leaders, and what preparation was required. The study was undertaken in 2009. Framework analysis techniques were employed to analyse the data. FINDINGS: A 'quasi-family' model of leadership emerged, with significant emphasis on the importance of personal relationships and support. Nursing grade had a greater impact on perceptions of leadership than geographical context or professional and clinical focus. CONCLUSION: No clear fit with any existing theoretical framework was identified. However, nurses in the highest grade banding, in particular, demonstrated practices associated with transformational leadership. Nurses expressed the very clear need to be acknowledged, respected and valued, and that those who provided this support were regarded as good leaders. PMID- 22077955 TI - Regioselective stepwise bromination of boron dipyrromethene (BODIPY) dyes. AB - Halogenated BODIPYs are important synthetic precursors and potential sensitizers for photodynamic therapy (PDT). Electrophilic bromination of pyrrolic unsubstituted BODIPYs using bromine regioselectively generated mono- to heptabromoBODIPYs in a stepwise fashion in good to excellent yields. These resultant bromoBODIPYs were applied for regioselective substitution and Suzuki coupling reaction to generate BODIPYs 4, 5, 6, and 7 in good to excellent yields. According to NMR and X-ray analysis results, the stepwise bromination first takes place at 2,6-, then at 3,5-, and eventually at 1,7-positions, whereas the regioselective substitution occurs first at 3,5- then at 1,7-positions of the chromophore. The spectroscopic properties of these resultant BODIPYs were studied, which shows the potential application of these bromoBODIPYs as sensitizers for PDT. PMID- 22077957 TI - The use of high doses of OROS hydromorphone in an acute palliative care unit. AB - OBJECTIVES: To characterize patients who received high doses of OROS hydromorphone (OROD-HY), a retrospective study of patients admitted in an acute pain relief and palliative care unit for a period of two years (from June 2009 to June 2011) was performed. METHODS: Globally, 79 patients were prescribed OROS-HY during admission at mean maximum doses of 68 mg/day (+/-42). Twenty-two patients were switched from other opioids to OROS-HY and 16 patients were switched from OROS-HY to other opioids. Sixty-three patients were discharged home with a prescription of OROS-HY with doses of 53 mg/day (+/-44). Doses were significantly lower in older patients (p < 0.005). The mean admission time was 6.1 days (+/ 3.2). During admission 10 patients (12.6%) were prescribed doses of OROS-HY of more than 64 mg/day. RESULTS: The maximum mean doses of this group of patients reached during admission were 238 mg/day. Eight of them were successfully treated and discharged home with doses of 175 mg/day. Two patients did not achieve an adequate balance between analgesia and adverse effects and received alternative treatments. CONCLUSION: This study demonstrated that OROS-HY administered in larger doses was relatively safe and effective, showing versatility and flexibility similar to other opioids. PMID- 22077956 TI - Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr. AB - BACKGROUND: Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo cell death. Thus, cells have evolved an elegant system in response to ionizing radiation induced DNA damage, where p53, Hsp70 and/or EGFr may play an important role in the process. In the present study, we investigated whether the content of p53, Hsp70 and EGFr are associated to glioblastoma (GBM) cell radioresistance. METHODS: Spheroids from U-87MG and MO59J cell lines as well as spheroids derived from primary culture of tumor tissue of one GBM patient (UGBM1) were irradiated (5, 10 and 20 Gy), their relative radioresistance were established and the p53, Hsp70 and EGFr contents were immunohistochemically determined. Moreover, we investigated whether EGFr-phospho Akt and EGFr-MEK-ERK pathways can induce GBM radioresistance using inhibitors of activation of ERK (PD098059) and Akt (wortmannin). RESULTS: At 5 Gy irradiation UGBM1 and U-87MG spheroids showed growth inhibition whereas the MO59J spheroid was relatively radioresistant. Overall, no significant changes in p53 and Hsp70 expression were found following 5 Gy irradiation treatment in all spheroids studied. The only difference observed in Hsp70 content was the periphery distribution in MO59J spheroids. However, 5 Gy treatment induced a significant increase on the EGFr levels in MO59J spheroids. Furthermore, treatment with inhibitors of activation of ERK (PD098059) and Akt (wortmannin) leads to radiosensitization of MO59J spheroids. CONCLUSIONS: These results indicate that the PI3K-Akt and MEK-ERK pathways triggered by EGFr confer GBM radioresistance. PMID- 22077959 TI - Field-scale reduction of PCB bioavailability with activated carbon amendment to river sediments. AB - Remediation of contaminated sediments remains a technological challenge because traditional approaches do not always achieve risk reduction goals for human health and ecosystem protection and can even be destructive for natural resources. Recent work has shown that uptake of persistent organic pollutants such as polychlorinated biphenyls (PCBs) in the food web is strongly influenced by the nature of contaminant binding, especially to black carbon surfaces in sediments. We demonstrate for the first time in a contaminated river that application of activated carbon to sediments in the field reduces biouptake of PCBs in benthic organisms. After treatment with activated carbon applied at a dose similar to the native organic carbon of sediment, bioaccumulation in freshwater oligochaete worms was reduced compared to preamendment conditions by 69 to 99%, and concentrations of PCBs in water at equilibrium with the sediment were reduced by greater than 93% at all treatment sites for up to three years of monitoring. By comparing measured reductions in bioaccumulation of tetra- and penta-chlorinated PCB congeners resulting from field application of activated carbon to a laboratory study where PCBs were preloaded onto activated carbon, it is evident that equilibrium sorption had not been achieved in the field. Although other remedies may be appropriate for some highly contaminated sites, we show through this pilot study that PCB exposure from moderately contaminated river sediments may be managed effectively through activated carbon amendment in sediments. PMID- 22077958 TI - Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures. AB - AIM: To report several types of response of immature permanent teeth with infected necrotic pulp tissue and either apical periodontitis or abscess to revascularization procedures. METHODOLOGY: Twenty immature permanent teeth with infected necrotic pulp tissue and either apical periodontitis or abscesses from 20 patients were included. The teeth were isolated with rubber dam, and pulp chambers was accessed through the crowns. The canals were gently irrigated with 5.25% sodium hypochlorite with minimal mechanical debridement. Calcium hydroxide was used as an inter-appointment intracanal medicament and placed into the coronal half of the canal space. After resolution of clinical signs and symptoms, bleeding was induced into the canal space from the periapical tissues using K files. The coronal canal space was sealed with a mixture of mineral trioxide aggregate (MTA) and saline solution. The access cavity was filled with composite resin. These immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscesses were followed up from 6 to 26 months. RESULTS: Five types of responses of these immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures were observed: type 1, increased thickening of the canal walls and continued root maturation; type 2, no significant continuation of root development with the root apex becoming blunt and closed; type 3, continued root development with the apical foramen remaining open; type 4, severe calcification (obliteration) of the canal space; type 5, a hard tissue barrier formed in the canal between the coronal MTA plug and the root apex. CONCLUSIONS: Based on this case series, the outcome of continued root development was not as predictable as increased thickening of the canal walls in human immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess after revascularization procedures. Continued root development of revascularized immature permanent necrotic teeth depends on whether the Hertwig's epithelial root sheath survives in case of apical periodontitis/abscess. Severe pulp canal calcification (obliteration) by hard tissue formation might be a complication of internal replacement resorption or union between the intracanal hard tissue and the apical bone (ankylosis) in revascularized immature permanent necrotic teeth. PMID- 22077960 TI - Peripheral CD300a+CD8+ T lymphocytes with a distinct cytotoxic molecular signature increase in pregnant women with chronic chorioamnionitis. AB - PROBLEM: CD300a is an immunomodulatory molecule of the immunoglobulin receptor superfamily expressed in the leukocytes of myeloid and lymphoid lineages. However, its biological function on CD8+ T lymphocytes remains largely unknown. This study was conducted to assess the biological significance of CD300a expression in T lymphocytes and to determine whether its expression in peripheral T lymphocytes changes in pregnant women presenting with antifetal rejection. METHODS OF STUDY: Microarray analysis was performed using total RNA isolated from peripheral CD300a+ and CD300a- T lymphocytes. Flow cytometric analysis of the peripheral blood samples of pregnant women and pathologic examination of the placentas were conducted. RESULTS: A large number of genes (N = 1245) were differentially expressed between CD300a- and CD300a+ subsets of CD8+ T lymphocytes, which included CCR7, CD244, CX3CR1, GLNY, GZMB, GZMK, IL15, ITGB1, KLRG1, PRF1, and SLAMF7. Gene ontology analysis of differentially expressed genes demonstrated enrichment of biological processes such as immune response, cell death, and signal transduction. CD300a expression in CD8+ T lymphocytes was coupled to a more cytotoxic molecular signature. Of note, the proportion of CD300a+CD8+ T lymphocytes increased in pregnant women with chronic chorioamnionitis (antifetal rejection of the chorioamniotic membranes; P < 0.05). CONCLUSION: The findings of this study strongly suggest an increase in systemic T-lymphocyte-mediated cytotoxicity in pregnant women with chronic chorioamnionitis as a manifestation of maternal antifetal rejection. PMID- 22077961 TI - Higher free thyroxine levels are associated with frailty in older men: the Health In Men Study. AB - OBJECTIVE: Frailty is common in the elderly and predisposes to ill-health. Some symptoms of frailty overlap those of thyroid dysfunction, but it is unclear whether differences in thyroid status influence risk of frailty. We evaluated associations between thyroid status and frailty in older men. DESIGN: Cross sectional epidemiological study. PARTICIPANTS: Community-dwelling men aged 70-89 years. MEASUREMENTS: Circulating thyrotropin (TSH) and free thyroxine (FT(4) ) were assayed. Frailty was assessed as >=3 of the Fatigue, Resistance, Ambulation, Illnesses and Loss (FRAIL) scale's 5 domains: fatigue; resistance (difficulty climbing flight of stairs); ambulation (difficulty walking 100 m); illness (>5); or weight loss (>5%), blinded to hormone results. RESULTS: Of 3943 men, 27 had subclinical hyperthyroidism, 431 subclinical hypothyroidism and 608 were classified as being frail (15.4%). There was an inverse log-linear association of TSH with FT(4). There was no association between TSH and frailty. After adjusting for covariates, men with FT(4) in the highest two quartiles had increased odds of being frail (Q3:Q1, odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.01 1.73 and Q4:Q1, OR = 1.36, 95% CI = 1.04-1.79, P = 0.010 for trend). Higher FT(4) was associated with fatigue (P = 0.038) and weight loss (P < 0.001). The association between FT(4) and frailty remained significant when the analysis was restricted to euthyroid men. CONCLUSIONS: High-normal FT(4) level is an independent predictor of frailty among ageing men. This suggests that even within the euthyroid range, circulating thyroxine may contribute to reduced physical capability. Further studies are needed to clarify the utility of thyroid function testing and the feasibility of preventing or reversing frailty in older men. PMID- 22077962 TI - Efficacy and safety of topical WBI-1001 in patients with mild to moderate psoriasis: results from a randomized double-blind placebo-controlled, phase II trial. AB - BACKGROUND: There is a need for the development of novel non-steroidal topical drugs for the treatment of psoriasis. OBJECTIVE: To assess the efficacy and safety of topical 1.0% WBI-1001 in patients with mild to moderate plaque psoriasis. METHODS: A total of 61 patients with 1-10% body surface area (BSA) covered with plaque psoriasis and a physician's global assessment score (PGA) of 2-4 were randomized (2:1) to receive either 1% WBI-1001 in a cream formulation or placebo, applied twice daily for 12 weeks. Efficacy was evaluated using PGA, BSA and Psoriasis Area and Severity Index (PASI). The primary endpoint was the change from baseline (Day 0) in PGA at week 12. RESULTS: The improvement in PGA at week 12 was 62.8% for patients randomized to WBI-1001 when compared with 13.0% for patients randomized to placebo (P<0.0001). At week 12, the proportion of patients who achieved a PGA of clear or almost clear and the mean improvement in BSA were 67.5% and 79.1%, respectively, for patients randomized to WBI-1001, when compared with 4.8% (P<0.0001) and an increase of 9.4% (P<0.0001), respectively, for patients randomized to placebo. More application site adverse drug reactions were observed in patients randomized to WBI-1001 than in those randomized to placebo. These adverse drug reactions were all mild or moderate in intensity. CONCLUSION: Topical WBI-1001 induces rapid and significant improvement in patients with plaque psoriasis. PMID- 22077963 TI - Predictive factors for urinary retention following kidney transplantation in male patients. AB - OBJECTIVE: Urinary retention frequently occurs in patients after kidney transplantation. This study aimed to identify predictive factors for urinary retention requiring transurethral resection of the prostate (TURP) following kidney transplantation. MATERIAL AND METHODS: Seventy male patients (median age 56 years, range 37-73 years) who underwent kidney transplantation between 1995 and 2006, and experienced urinary retention and consecutively required TURP, were studied retrospectively. Residual diuresis before transplantation, duration of dialysis, patient age, prostate size, rejection reactions, transplant loss, combined kidney and pancreas transplantation, type 1 and 2 diabetes mellitus, and carcinoma of the prostate were evaluated as predictive factors. RESULTS: Duration of dialysis longer than 120 months (p = 0.0174), patient age over 60 years (p = 0.0045) and the absence of diabetes (n = 46, p = 0.0029) were associated with a significantly higher risk of urinary retention requiring TURP following kidney transplantation. Residual diuresis, prostate size, frequency of rejection reactions, transplant loss and detection of carcinoma, however, could not be identified as predictive factors. CONCLUSIONS: In male patients after kidney transplantation with a long history of dialysis, early TURP due to urinary retention must be anticipated. Surprisingly, the presence of type 1 or 2 diabetes seems to prevent the occurrence of retention, independently of age. PMID- 22077964 TI - Extensive polymorphism in the porcine Toll-like receptor 10 gene. AB - The great importance of the Toll-like receptors (TLRs) in innate immunity is well established, but one family member--TLR10--remains elusive. TLR10 is expressed in various tissues in several species, but its ligand is not known and its function is still poorly understood. The open reading frame of TLR10 was sequenced in 15 wild boars, representing three populations, and in 15 unrelated domestic pigs of Hampshire, Landrace and Large White origin. Amino acid positions corresponding to detected nonsynonymous single nucleotide polymorphisms (SNPs) were analysed in the crystal structures determined for the human TLR1-TLR2-lipopeptide complex and the human TLR10 Toll/Interleukin 1 receptor (TIR) dimer. SNP occurrence in wild boars and domestic pigs was compared, and haplotypes for the TLR10 gene and the TLR6-1-10 gene cluster were reconstructed. Despite the limited number of animals sequenced in the present study (N = 30), a larger number of SNPs were found in TLR10 than recently reported for TLR1, TLR6 and TLR2. Thirty-three SNPs were detected, of which 20 were nonsynonymous. The relative frequency of nonsynonymous (d(N) ) and synonymous (d(S) ) SNPs between wild boars and domestic pigs was higher in TLR10 than recently reported for TLR1, TLR6 and TLR2. However, the polymorphism reported in the present study seems to leave the function of the TLR10 molecule unaffected. Furthermore, no nonsynonymous SNPs were detected in the part of the gene corresponding to the hinge region of the receptor, probably reflecting rigorously acting functional constraint. The total number of SNPs and the number of nonsynonymous SNPs were significantly lower (P < 0.05) in the wild boars than in the domestic pigs, and fewer TLR10 haplotypes were present in the wild boars. The majority of the TLR6-1-10 haplotypes were specific for either wild boars or domestic pigs, probably reflecting differences in microbial environment and population history. PMID- 22077965 TI - Carry-over effect of host nutritional quality on performance of spruce budworm progeny. AB - The effect of host nutritional quality on spruce budworm (Choristoneura fumiferana (Clemens)) parental and offspring performance was studied using field and laboratory rearing experiments, and foliar chemical analyses. Foliage of balsam fir (Abies balsamea (L.) Mill.), white spruce (Picea glauca (Moench) Voss) and black spruce (P. mariana (Mill.) BSP) was used to rear the parental generation in the field, whereas an artificial diet was used to rear the progeny under laboratory conditions. Important differences in the food quality were provided by the three hosts. Black spruce foliage had higher concentrations of certain monoterpene deterrents and total phenolics, together with stronger seasonal declines in nutrients such as N, P and Mg, compared with the other hosts. We hypothesise that this trend may be related to poor performance and survival of the progeny. Laboratory rearing showed that progeny of parents that fed on black spruce exhibited longer developmental times and greater mortality, and had lower pupal mass than progeny of parents fed on the other hosts. Further, artificial food-fed progeny of insects reared on black spruce reached sixth instar later, with lower mass, and exhibited higher relative growth rate (RGR) than progeny of parents fed on the other hosts. These results suggest nutritionally-based parental effects. These results also confirmed that the quality of food consumed by the parents can influence the fitness of the next generation. PMID- 22077966 TI - Monofunctionalization of protein nanocages. AB - Surface monofunctionalization of protein nanostructures will enable precise topological control over the protein-templated assembly of nanoscale motifs, however, this remains a formidable challenge. Here we demonstrated a novel strategy for this purpose with a protein nanocage, virus-based nanoparticle (VNP) of simian virus 40 as a model system. By simultaneously incorporating a function modality (cysteine) and a purification modality (polyhistidine tag) into the building block (VP1) of VNPs through rational design and genetic engineering, the monofunctionalized cysteine-VNPs are readily obtained through a routine affinity chromatography in virtue of the purification modality of polyhistidine tag, after the coassembly of the functional VP1 and the nonfunctional VP1 at an optimal ratio. This strategy has proved to be highly efficient in constructing monofunctionalized protein nanostructures as highlighted by the monofunctionalized-VNP-guided Au/QD-VNP nanostructures. These nanostructures could be utilized in a wide range of disciplines, including basic biological research, novel nanostructures, and nanodevices fabrication, etc. PMID- 22077967 TI - Infrared spectroscopy of wafer-scale graphene. AB - We report spectroscopy results from the mid- to far-infrared on wafer-scale graphene, grown either epitaxially on silicon carbide or by chemical vapor deposition. The free carrier absorption (Drude peak) is simultaneously obtained with the universal optical conductivity (due to interband transitions) and the wavelength at which Pauli blocking occurs due to band filling. From these, the graphene layer number, doping level, sheet resistivity, carrier mobility, and scattering rate can be inferred. The mid-IR absorption of epitaxial two-layer graphene shows a less pronounced peak at 0.37 +/- 0.02 eV compared to that in exfoliated bilayer graphene. In heavily chemically doped single-layer graphene, a record high transmission reduction due to free carriers approaching 40% at 250 MUm (40 cm(-1)) is measured in this atomically thin material, supporting the great potential of graphene in far-infrared and terahertz optoelectronics. PMID- 22077968 TI - Analysis of medication errors of health care providers on the basis of data from the Czech Toxicological Information Centre over an 11-year period (2000-2010). AB - This study aimed to analyse medication errors committed by health care professionals leading to toxicological consultations at the Czech Toxicological Information Centre and to identify the categories of special concern for further interventions of health care quality experts. PMID- 22077969 TI - Characterization of the genome of bald cypress. AB - BACKGROUND: Bald cypress (Taxodium distichum var. distichum) is a coniferous tree of tremendous ecological and economic importance. It is a member of the family Cupressaceae which also includes cypresses, redwoods, sequoias, thujas, and junipers. While the bald cypress genome is more than three times the size of the human genome, its 1C DNA content is amongst the smallest of any conifer. To learn more about the genome of bald cypress and gain insight into the evolution of Cupressaceae genomes, we performed a Cot analysis and used Cot filtration to study Taxodium DNA. Additionally, we constructed a 6.7 genome-equivalent BAC library that we screened with known Taxodium genes and select repeats. RESULTS: The bald cypress genome is composed of 90% repetitive DNA with most sequences being found in low to mid copy numbers. The most abundant repeats are found in fewer than 25,000 copies per genome. Approximately 7.4% of the genome is single/low-copy DNA (i.e., sequences found in 1 to 5 copies). Sequencing of highly repetitive Cot clones indicates that most Taxodium repeats are highly diverged from previously characterized plant repeat sequences. The bald cypress BAC library consists of 606,336 clones (average insert size of 113 kb) and collectively provides 6.7-fold genome equivalent coverage of the bald cypress genome. Macroarray screening with known genes produced, on average, about 1.5 positive clones per probe per genome-equivalent. Library screening with Cot-1 DNA revealed that approximately 83% of BAC clones contain repetitive sequences iterated 103 to 104 times per genome. CONCLUSIONS: The BAC library for bald cypress is the first to be generated for a conifer species outside of the family Pinaceae. The Taxodium BAC library was shown to be useful in gene isolation and genome characterization and should be an important tool in gymnosperm comparative genomics, physical mapping, genome sequencing, and gene/polymorphism discovery. The single/low-copy (SL) component of bald cypress is 4.6 times the size of the Arabidopsis genome. As suggested for other gymnosperms, the large amount of SL DNA in Taxodium is likely the result of divergence among ancient repeat copies and gene/pseudogene duplication. PMID- 22077970 TI - Abundant pleiotropy in human complex diseases and traits. AB - We present a systematic review of pleiotropy among SNPs and genes reported to show genome-wide association with common complex diseases and traits. We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pleiotropic effects. SNP pleiotropic status was associated with gene location (p = 0.024; pleiotropic SNPs more often exonic [14.5% versus 4.9% for nonpleiotropic, trait-associated SNPs] and less often intergenic [15.8% versus 23.6%]), "predicted transcript consequence" (p = 0.001; pleiotropic SNPs more often predicted to be structurally deleterious [5% versus 0.4%] but not more often in regulatory sequences), and certain disease classes. We develop a method to calculate the likelihood that pleiotropic links between traits occurred more often than expected and demonstrate that this approach can identify etiological links that are already known (such as between fetal hemoglobin and malaria risk) and those that are not yet established (e.g., between plasma campesterol levels and gallstones risk; and between immunoglobulin A and juvenile idiopathic arthritis). Examples of pleiotropy will accumulate over time, but it is already clear that pleiotropy is a common property of genes and SNPs associated with disease traits, and this will have implications for identification of molecular targets for drug development, future genetic risk-profiling, and classification of diseases. PMID- 22077971 TI - A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe-S proteins. AB - We report on ten individuals with a fatal infantile encephalopathy and/or pulmonary hypertension, leading to death before the age of 15 months. Hyperglycinemia and lactic acidosis were common findings. Glycine cleavage system and pyruvate dehydrogenase complex (PDHC) activities were low. Homozygosity mapping revealed a perfectly overlapping homozygous region of 1.24 Mb corresponding to chromosome 2 and led to the identification of a homozygous missense mutation (c.622G > T) in NFU1, which encodes a conserved protein suggested to participate in Fe-S cluster biogenesis. Nine individuals were homozygous for this mutation, whereas one was compound heterozygous for this and a splice-site (c.545 + 5G > A) mutation. The biochemical phenotype suggested an impaired activity of the Fe-S enzyme lipoic acid synthase (LAS). Direct measurement of protein-bound lipoic acid in individual tissues indeed showed marked decreases. Upon depletion of NFU1 by RNA interference in human cell culture, LAS and, in turn, PDHC activities were largely diminished. In addition, the amount of succinate dehydrogenase, but no other Fe-S proteins, was decreased. In contrast, depletion of the general Fe-S scaffold protein ISCU severely affected assembly of all tested Fe-S proteins, suggesting that NFU1 performs a specific function in mitochondrial Fe-S cluster maturation. Similar biochemical effects were observed in Saccharomyces cerevisiae upon deletion of NFU1, resulting in lower lipoylation and SDH activity. Importantly, yeast Nfu1 protein carrying the individuals' missense mutation was functionally impaired. We conclude that NFU1 functions as a late-acting maturation factor for a subset of mitochondrial Fe-S proteins. PMID- 22077972 TI - Muscarinic Acetylcholine Receptor M3 Mutation Causes Urinary Bladder Disease and a Prune-Belly-like Syndrome. AB - Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice. PMID- 22077973 TI - Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome. AB - Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS or Ohdo syndrome) is a multiple anomaly syndrome characterized by severe intellectual disability, blepharophimosis, and a mask-like facial appearance. A number of individuals with SBBYSS also have thyroid abnormalities and cleft palate. The condition usually occurs sporadically and is therefore presumed to be due in most cases to new dominant mutations. In individuals with SBBYSS, a whole-exome sequencing approach was used to demonstrate de novo protein-truncating mutations in the highly conserved histone acetyltransferase gene KAT6B (MYST4/MORF)) in three out of four individuals sequenced. Sanger sequencing was used to confirm truncating mutations of KAT6B, clustering in the final exon of the gene in all four individuals and in a further nine persons with typical SBBYSS. Where parental samples were available, the mutations were shown to have occurred de novo. During mammalian development KAT6B is upregulated specifically in the developing central nervous system, facial structures, and limb buds. The phenotypic features seen in the Qkf mouse, a hypomorphic Kat6b mutant, include small eyes, ventrally placed ears and long first digits that mirror the human phenotype. This is a further example of how perturbation of a protein involved in chromatin modification might give rise to a multisystem developmental disorder. PMID- 22077974 TI - Accuracy of two-dimensional echocardiography in determining aortic valve structure in patients >50 years of age having aortic valve replacement for aortic stenosis. AB - We sought to measure the accuracy of 2-dimensional transthoracic echocardiography in determining aortic valve structure in patients with aortic stenosis (AS) undergoing aortic valve replacement (AVR). Few studies have compared aortic valve structure determined by echocardiogram to that determined by examination of the operatively excised stenotic aortic valve. Two-dimensional echocardiograms were reviewed and interpreted by an expert echocardiographer in blinded fashion in 100 patients >50 years of age (mean 70) who had undergone AVR for isolated AS +/- aortic regurgitation and the aortic valve structure (unicuspid, bicuspid, tricuspid) was compared to that from examination of the operatively excised stenotic valve. After excluding 14 cases in which echocardiograms were uninterpretable because of heavy calcium and/or poor image quality, congenitally malformed valves were present in 44 patients (51%) and tricuspid valves in 42 of the 86 patients (49%). Ten of the 14 patients (71%) with uninterpretable echocardiograms had congenitally malformed valves. Valve structure by echocardiogram was concordant with morphologic interpretation in 57 of 86 patients (66% accuracy, kappa = 0.33). Accuracy trended toward improvement as degree of AS decreased. In patients with valve areas similar to those enrolled in the recent transcatheter aortic valve implantation trial (PARTNER; 0.7 +/- 0.2 cm(2)), aortic valve structure was accurately determined by echocardiography in 21 of 35 patients (60%). In conclusion, aortic valve structure was interpretable by transthoracic echocardiogram in 86 of 100 patients and accurate in 57 of these 86 patients (66%). PMID- 22077975 TI - Aortic medial elastic fiber loss in acute ascending aortic dissection. AB - The cause of acute aortic dissection continues to be debated. One school of thought suggests that underlying aortic medial cystic necrosis is the common denominator. The purpose of the present study was to determine if there was loss and, if so, how much loss of medial elastic fibers in the ascending aorta in patients with acute aortic dissection with the entrance tear in the ascending aorta. We examined operatively excised ascending aortas in 69 patients having acute dissection with tears in the ascending aorta. Patients with previous aortotomy, healed dissection, and connective tissue disorders were excluded. The 69 patients' ages ranged from 31 to 88 years (mean 56); 49 were men and 20 were women. Loss of aortic medial elastic fibers was graded as 0 (no loss), 1+ (trace), 2+ (mild), 3+ (moderate), and 4+ (full thickness loss). Of these 69 patients, 56 (82%) had 0 or 1+ elastic fiber loss; 13 patients (18%), 2+ to 4+ loss including 4 with 2+, 6 with 3+, and 2 with 4+. Nearly all patients (97%) had a history of systemic hypertension and/or had received antihypertensive drug therapy. In conclusion, most patients (82% in this study) having acute aortic dissection with entrance tears in the ascending aorta have normal numbers or only trace loss of aortic medial elastic fibers. Thus, underlying abnormal ascending aortic structure uncommonly precedes acute dissection. PMID- 22077976 TI - Frequency and relevance of ischemic electrocardiographic findings in patients with chronic obstructive pulmonary disease. AB - Cardiovascular disease is common in patients with chronic obstructive pulmonary disease (COPD) but often remains unrecognized. Ischemic electrocardiographic (ECG) changes are associated with a higher risk of dying from coronary heart disease but have never been systematically evaluated in COPD. Also, their relation to clinical outcome has not been studied. We aimed to determine the frequency of ischemic ECG changes and its relevance in relation to clinical outcome and predictors of impaired survival in patients with COPD. Clinical characteristics, pulmonary function, and co-morbidities were assessed in 536 patients with COPD during baseline assessment of a comprehensive pulmonary rehabilitation program. Moreover, electrocardiograms at rest were obtained in all patients. All electrocardiograms were scored independently by 2 cardiologists using the Minnesota scoring system. Major or minor Q or QS pattern, ST junction and segment depression, T-wave items, or left bundle branch block were considered ischemic ECG changes. One hundred thirteen patients (21%) had ischemic ECG changes. Moreover, 42 of 293 patients (14%) without self-reported cardiovascular co-morbidities had ischemic ECG changes. In addition, patients with ischemic ECG changes had higher dyspnea grades (Modified Medical Research Council (mMRC) 2.9 +/- 1.1 vs 2.6 +/- 1.1, p = 0.032), worse exercise performance (6-minute walking distance 387 +/- 126 vs 425 +/- 126 m, p = 0.004), more systemic inflammation (high-sensitivity C-reactive protein 11.2 +/- 16.2 vs 7.9 +/- 10.7 mmol/l, p = 0.01), higher scores on the Charlson Co-morbidity Index (1.8 +/- 0.9 vs 1.5 +/- 0.8 points), and higher scores BODE (5.3 +/- 3.7 vs 4.5 +/- 3.4 points, p = 0.033) and on ADO indexes (5.2 +/- 1.7 vs 4.8 +/- 1.7 points, p = 0.029) compared to patients without ischemic ECG changes, whereas forced expiratory volume in the first second was similar (40.8 +/- 15.2% vs 42.6% +/- 15.9%, p = 0.30). In conclusion, ischemic ECG changes are common in patients with COPD and associated with poor clinical outcome irrespective of forced expiratory volume in the first second. These results suggest an important role for cardiovascular disease in impaired survival in these patients. PMID- 22077977 TI - Rotational mechanics of the left ventricle in amyloid light chain amyloidosis. PMID- 22077978 TI - Underuse of anticoagulants in atrial fibrillation. PMID- 22077979 TI - Flow limitation in coronary artery disease. PMID- 22077980 TI - Anticoagulation in non-valvular atrial fibrillation: underused or wrongly used? PMID- 22077981 TI - Anti-CTLA4 monoclonal antibodies: the past and the future in clinical application. AB - Recently, two studies using ipilimumab, an anti-CTLA-4 monoclonal antibody (mab) demonstrated improvements in overall survival in the treatment of advanced melanoma. These studies utilized two different schedules of treatment in different patient categories (first and second line of treatment). However, the results were quite similar despite of different dosage used and the combination with dacarbazine in the first line treatment. We reviewed the result of randomized phase II-III clinical studies testing anti-CTLA-4 antibodies (ipilimumab and tremelimumab) for the treatment of melanoma to focus on practical or scientific questions related to the broad utilization of these products in the clinics. These analyses raised some considerations about the future of these compounds, their potential application, dosage, the importance of the schedule (induction/manteinance compared to induction alone) and their role as adjuvants. Anti-CTLA-4 antibody therapy represents the start of a new era in the treatment of advanced melanoma but we are on the steep slope of the learning curve toward the optimization of their utilization either a single agents or in combination. PMID- 22077982 TI - Basal progenitor cells in the embryonic mouse thalamus - their molecular characterization and the role of neurogenins and Pax6. AB - BACKGROUND: The size and cell number of each brain region are influenced by the organization and behavior of neural progenitor cells during embryonic development. Recent studies on developing neocortex have revealed the presence of neural progenitor cells that divide away from the ventricular surface and undergo symmetric divisions to generate either two neurons or two progenitor cells. These 'basal' progenitor cells form the subventricular zone and are responsible for generating the majority of neocortical neurons. However, not much has been studied on similar types of progenitor cells in other brain regions. RESULTS: We have identified and characterized basal progenitor cells in the embryonic mouse thalamus. The progenitor domain that generates all of the cortex-projecting thalamic nuclei contained a remarkably high proportion of basally dividing cells. Fewer basal progenitor cells were found in other progenitor domains that generate non-cortex projecting nuclei. By using intracellular domain of Notch1 (NICD) as a marker for radial glial cells, we found that basally dividing cells extended outside the lateral limit of radial glial cells, indicating that, similar to the neocortex and ventral telencephalon, the thalamus has a distinct subventricular zone. Neocortical and thalamic basal progenitor cells shared expression of some molecular markers, including Insm1, Neurog1, Neurog2 and NeuroD1. Additionally, basal progenitor cells in each region also expressed exclusive markers, such as Tbr2 in the neocortex and Olig2 and Olig3 in the thalamus. In Neurog1/Neurog2 double mutant mice, the number of basally dividing progenitor cells in the thalamus was significantly reduced, which demonstrates the roles of neurogenins in the generation and/or maintenance of basal progenitor cells. In Pax6 mutant mice, the part of the thalamus that showed reduced Neurog1/2 expression also had reduced basal mitosis. CONCLUSIONS: Our current study establishes the existence of a unique and significant population of basal progenitor cells in the thalamus and their dependence on neurogenins and Pax6. These progenitor cells may have important roles in enhancing the generation of neurons within the thalamus and may also be critical for generating neuronal diversity in this complex brain region. PMID- 22077983 TI - Evidence of a role for Th17 cells in the breach of immune tolerance in arthritis. AB - Th17 cells are thought to play a pathogenic role in various autoimmune diseases. Cytokines secreted by Th17 cells like IL-17, IL-17F and IL-22 have the capacity to mediate a massive inflammatory response. These proinflammatroy cytokines are likely to mediate the pathogenic potential of Th17 cells. Recent evidence suggests a role for Th17 cells in the breach of immune tolerance. This might shed some new light on the pathogenic role of Th17 cells in autoimmunity. PMID- 22077984 TI - Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels. AB - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF-I, GH-binding protein (GHBP), IGF-binding proteins (IGFBPs) and acid-labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet. AIM OF THE STUDY: To explore whether GH secretion and/or levels of IGF-I, IGFBP 3, ALS and GHBP could be altered in obese patients in relation to the presence of liver steatosis. MATERIALS AND METHODS: A total of 115 obese patients (BMI > 30) were enrolled in the protocol (65 patients with liver steatosis and 50 age- and BMI-matched controls). In all patients, the following parameters were studied: serum levels of glucose, insulin, the HOMA index, IGF-I, GHBP, IGFBP-3, ALS and GH after GHRH and arginine stimulation test. RESULTS: As expected, patients with NAFLD had blood glucose, insulin, HOMA-R significantly higher than controls, indicating a more severe insulin-resistance state in NAFLD. Furthermore, patients with NAFLD had higher levels of GHBP and IGFBP-3 and lower GH peak and IGF-I levels as compared to controls. No difference was found in ALS levels between the groups. In a multivariate analysis, GHBP was positively associated with hepatic steatosis while IGF-1 was negatively associated with hepatic steatosis. CONCLUSIONS: This study demonstrates that in patients with NAFLD, the GHBP levels are increased, and that the GH/IGF-I axis is significantly altered probably leading to reduced IGF-I bioavailability at tissue level. PMID- 22077985 TI - Development of a brief multidisciplinary education programme for patients with osteoarthritis. AB - BACKGROUND: Osteoarthritis (OA) is a prevalent progressive musculoskeletal disorder, leading to pain and disability. Patient information and education are considered core elements in treatment guidelines for OA; however, there is to our knowledge no evidence-based recommendation on the best approach, content or length on educational programmes in OA. OBJECTIVE: to develop a brief, patient oriented disease specific multidisciplinary education programme (MEP) to enhance self-management in patients with OA. METHOD: Twelve persons (80% female mean age 59 years) diagnosed with hand, hip or knee OA participated in focus group interviews. In the first focus group, six participants were interviewed about their educational needs, attitudes and expectations for the MEP. The interviews were transcribed verbatim and thereafter condensed.Based on results from focus group interviews, current research evidence, clinical knowledge and patients' experience, a multidisciplinary OA team (dietist, nurse, occupational therapist, pharmacist, physical therapist and rheumatologist) and a patient representative developed a pilot-MEP after having attended a work-shop in health pedagogics. Finally, the pilot-MEP was evaluated by a second focus group consisting of four members from the first focus group and six other experienced patients, before final adjustments were made. RESULTS: The focus group interviews revealed four important themes: what is OA, treatment options, barriers and coping strategies in performing daily activities, and how to live with osteoarthritis. Identified gaps between patient expectations and experience with the pilot-programme were discussed and adapted into a final MEP. The final MEP was developed as a 3.5 hour educational programme provided in groups of 6-9 patients. All members from the multidisciplinary team are involved in the education programme, including a facilitator who during the provision of the programme ensures that the individual questions are addressed. As part of an ongoing process, a patient representative regularly attends the MEP and gives feedback concerning content and perceived value. CONCLUSION: A MEP has been developed to enhance self-management in patients with OA attending a multidisciplinary OA outpatient clinic. The effectiveness of the MEP followed by individual consultations with members of the multidisciplinary team is currently evaluated in a randomised controlled trial with respect to patient satisfaction and functioning. PMID- 22077986 TI - Effects of chemical, biological, and physical aging as well as soil addition on the sorption of pyrene to activated carbon and biochar. AB - In this study, the suitability of biochar and activated carbon (AC) for contaminated soil remediation is investigated by determining the sorption of pyrene to both materials in the presence and absence of soil and before as well as after aging. Biochar and AC were aged either alone or mixed with soil via exposure to (a) nutrients and microorganisms (biological), (b) 60 and 110 degrees C (chemical), and (c) freeze-thaw cycles (physical). Before and after aging, the pH, elemental composition, cation exchange capacity (CEC), microporous SA, and sorption isotherms of pyrene were quantified. Aging at 110 degrees C altered the physicochemical properties of all materials to the greatest extent (for example, pH increased by up to three units and CEC by up to 50% for biochar). Logarithmic K(Fr) values ranged from 7.80 to 8.21 (ng kg(-1))(ng L( 1))(-nF) for AC and 5.22 to 6.21 (ng kg(-1))(ng L(-1))(-nF) for biochar after the various aging regimes. Grinding biochar to a smaller particle size did not significantly affect the sorption of d(10) pyrene, implying that sorption processes operate on the subparticle scale. Chemical aging decreased the sorption of pyrene to the greatest extent (up to 1.8 log unit for the biochar+soil). The sorption to AC was affected more by the presence of soil than the sorption to biochar was. Our results suggest that AC and biochar have a high sorption capacity for pyrene that is maintained both in the presence of soil and during harsh aging. Both materials could therefore be considered in contaminated land remediation. PMID- 22077988 TI - The epidemiology of fractures of the proximal ulna. AB - INTRODUCTION: The aim of our study was to report the epidemiological characteristics of fractures of the proximal ulna. METHODS: From our prospective trauma database of 6872 fractures, we identified all acute fractures of the proximal ulna from a 1-year period between July 2007 and June 2008. Age, gender, mode of injury, fracture classifications, associated injuries and treatment were the factors documented and analysed. RESULTS: There were 78 fractures of the proximal ulna with a mean age of 57 years (15-97). Males (n=35) sustained their fracture at a significantly younger age than females (p=0.041), with no gender predominance seen (p=0.365). The overall fracture distribution was a unimodal older male and unimodal older female type-F curve. The most common mode of injury was a simple fall from standing height (n=52, 67%), with younger patients more likely to sustain their injuries following a high-energy mechanism such as sports or a motor vehicle collision (p<0.001). Seventeen (22%) patients sustained associated injuries to the ipsilateral limb, with an associated proximal radial fracture most frequent (n=13, 17%). Open fractures were seen in five (6.4%) patients. A total of 64 patients had a fracture of the olecranon, with the Mayo 2A most frequently seen (n=47, 60%). CONCLUSIONS: Fractures of the proximal ulna are fragility fractures that predominantly occur in elderly patients. Given the number of elderly patients sustaining these injuries, research is needed to determine the role of non-operative treatment for these fractures, particularly in patients with multiple co-morbidities and low functional demands. PMID- 22077989 TI - UK triage--an improved tool for an evolving threat. AB - INTRODUCTION: A key challenge at a major incident is to quickly identify those casualties most urgently needing treatment in order to survive - triage. The UK Triage Sieve (TS) advocated by the Major Incident Medical Management (MIMMS) Course categorises casualties by ability to walk, respiratory rate (RR) and heart rate (HR) or capillary refill time. The military version (MS) includes assessment of consciousness. We tested whether the MS better predicts need for life-saving intervention in a military trauma population. Ideal HR, RR and Glasgow Coma Score (GCS) thresholds were calculated. METHODS: A gold standard Priority 1 casualty was defined using resource-based criteria. Pre-hospital data from a military trauma database allowed calculation of triage category, which was compared with this standard, and presented as 2*2 tables. Sensitivity and specificity of each physiological parameter was calculated over a range of values to identify the ideal cut-offs. RESULTS: A gold standard could be ascribed in 1657 cases. In 1213 both the MS and TS could ascribe a category. MS was significantly more sensitive than TS (59% vs 53%, p<0.001) with similar specificity (89 vs 88%). Varying the limits for each parameter allowed some improvements in sensitivity (70-80%) but specificity dropped rapidly. DISCUSSION: Previous studies support the inclusion of GCS assessment for blunt as well as penetrating trauma. Optimising the physiological cut-offs increased sensitivity in this sample to only 71% - a Sieve based purely on physiological parameters may not be capable of an acceptable level of sensitivity. CONCLUSIONS: The MS is more sensitive than the TS. Major incident planners utilising the Sieve should consider adopting the military version as their first line triage tool. If validated, altering the HR and RR thresholds may further improve the tool. PMID- 22077987 TI - Global protein synthesis in human trophoblast is resistant to inhibition by hypoxia. AB - Placental growth and function depend on syncytial cell processes which require the continuing synthesis of cellular proteins. The substantial energy demands of protein synthesis are met primarily from oxidative metabolism. Although the responses of individual proteins produced by the syncytiotrophoblast to oxygen deprivation have been investigated previously, there is no information available on global protein synthesis in syncytiotrophoblast under conditions of hypoxia. These studies were designed to test the hypothesis that syncytial protein synthesis is decreased in a dose-dependent manner by hypoxia. Experiments were performed to measure amino acid incorporation into proteins in primary syncytiotrophoblast cells exposed to oxygen concentrations ranging from 0 to 10%. Compared to cells exposed to normoxia (10% O2), no changes were observed following exposure to 5% or 3% O2, but after exposure to 1% O2, protein synthesis after 24 and 48 h decreased by 24% and 23% and with exposure to 0% O2, by 65% and 50%. As a consequence of these results, we hypothesized that global protein synthesis in conditions of severe hypoxia was being supported by glucose metabolism. Additional experiments were performed therefore to examine the role of glucose in supporting protein synthesis. These demonstrated that at each oxygen concentration there was a significant, decreasing linear trend in protein synthesis as glucose concentration was reduced. Under conditions of near-anoxia and in the absence of glucose, protein synthesis was reduced by >85%. Even under normoxic conditions (defined as 10% O2) and in the presence of oxidative substrates, reductions in glucose were accompanied by decreases in protein synthesis. These experiments demonstrate that syncytiotrophoblast cells are resistant to reductions in protein synthesis at O2 concentrations greater than 1%. This could be explained by our finding that a significant fraction of protein synthesis in the syncytiotrophoblast is sustained by glycolytic metabolism. This suggests that with increasing degrees of chronic hypoxia there is a shift from oxidative to glycolytic pathways, allowing a substantial degree of protein synthesis to be maintained. PMID- 22077990 TI - Discharge destination following lower limb fracture: development of a prediction model to assist with decision making. AB - BACKGROUND: Accurate prediction of the likelihood of discharge to inpatient rehabilitation following lower limb fracture made on admission to hospital may assist patient discharge planning and decrease the burden on the hospital system caused by delays in decision making. AIMS: To develop a prognostic model for discharge to inpatient rehabilitation. METHOD: Isolated lower extremity fracture cases (excluding fractured neck of femur), captured by the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), were extracted for analysis. A training data set was created for model development and validation data set for evaluation. A multivariable logistic regression model was developed based on patient and injury characteristics. Models were assessed using measures of discrimination (C statistic) and calibration (Hosmer-Lemeshow (H-L) statistic). RESULTS: A total of 1429 patients met the inclusion criteria and were randomly split into training and test data sets. Increasing age, more proximal fracture type, compensation or private fund source for the admission, metropolitan location of residence, not working prior to injury and having a self-reported pre-injury disability were included in the final prediction model. The C-statistic for the model was 0.92 (95% confidence interval (CI) 0.88, 0.95) with an H-L statistic of chi(2)=11.62, p=0.17. For the test data set, the C-statistic was 0.86 (95% CI 0.83, 0.90) with an H-L statistic of chi(2)=37.98, p<0.001. CONCLUSION: A model to predict discharge to inpatient rehabilitation following lower limb fracture was developed with excellent discrimination although the calibration was reduced in the test data set. This model requires prospective testing but could form an integral part of decision making in regards to discharge disposition to facilitate timely and accurate referral to rehabilitation and optimise resource allocation. PMID- 22077991 TI - Stromal cell-derived factor-1 (SDF-1/CXCL12) gene polymorphisms in pulmonary tuberculosis patients of south India. AB - CXCL12 gene polymorphisms influence CXCL12 levels and may be associated with the outcome of host-pathogen interaction. Hence, the present study was carried out to find out whether CXCL12 gene polymorphisms are associated with susceptibility or resistance to pulmonary tuberculosis (PTB). Intron and 3' untranslated region (UTR) polymorphisms of CXCL12 gene were investigated among 184 patients with PTB and 187 healthy controls (HC) using polymerase chain reaction-based methods. The results revealed an increased frequency of G/A genotype of In2 +5887 [P = 0.034; odds ratio (OR) 1.66; 95% confidence intervals 1.04-2.66] and a decreased frequency of G/A genotype of 3'UTR +12197 polymorphisms (P = 0.051; OR 0.64; 95% CI 0.4-1.00) among patients than HCs. When the study subjects were categorized based on sex, significantly increased frequencies of G/A genotype (P = 0.013 P(c) = 0.039; OR 2.41) of In2 +5887 and G/G genotype (P = 0.005, P(c) = 0.015; OR 2.48) of 3'UTR +12197 polymorphisms were observed among female patients with PTB as compared to female HC. A significantly decreased frequency of the haplotype G C-A-T (P = 0.006, P(c) = 0.030; OR 0.48) was noticed among female patients with PTB as compared to female HC. The study suggests that G/A genotype of In2 +5887 and G/G genotype of 3'UTR +12197 polymorphisms may be associated with susceptibility to PTB among females, and the haplotype G-C-A-T of CXCL12 gene may be associated with protection in females. PMID- 22077992 TI - Lab-on-a-bubble: synthesis, characterization, and evaluation of buoyant gold nanoparticle-coated silica spheres. AB - This paper describes the development and preparation of a new class of materials for surface-enhanced Raman scattering (SERS) consisting of gold nanoparticles coated onto hollow, buoyant silica microspheres. These materials allow for a new type of molecular assay designated as a lab-on-a-bubble (LoB). LoB materials serve as a convenient platform for the detection of analytes in solution and offer several advantages over traditional colloidal gold and planar SERS substrates, such as the ability to localize and concentrate analytes for detection. An example assay is presented using the LoB method and cyanide detection. Cyanide binds to SERS-active, gold-coated LoBs and is detected directly from the corresponding SERS signal. The abilities of LoBs and a gold colloid to detect cyanide are compared, and in both cases, a detection limit of ~170 ppt was determined. Differences in measurement error using LoBs versus gold colloid are also described, as well as an assay for 5,5'-dithiobis(2-nitrobenzoic acid) that shows the benefit of using LoBs over SERS analyses in colloids, which are often plagued by particle aggregation. PMID- 22077993 TI - Biphasic peptide amphiphile nanomatrix embedded with hydroxyapatite nanoparticles for stimulated osteoinductive response. AB - Formation of the native bone extracellular matrix (ECM) provides an attractive template for bone tissue engineering. The structural support and biological complexity of bone ECM are provided within a composite microenvironment that consists of an organic fibrous network reinforced by inorganic hydroxyapatite (HA) nanoparticles. Recreating this biphasic assembly, a bone ECM analogous scaffold comprising self-assembling peptide amphiphile (PA) nanofibers and interspersed HA nanoparticles was investigated. PAs were endowed with biomolecular ligand signaling using a synthetically inscribed peptide sequence (i.e., RGDS) and integrated with HA nanoparticles to form a biphasic nanomatrix hydrogel. It was hypothesized the biphasic hydrogel would induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) and improve bone healing as mediated by RGDS ligand signaling within PA nanofibers and embedded HA mineralization source. Viscoelastic stability of the biphasic PA hydrogels was evaluated with different weight concentrations of HA for improved gelation. After demonstrating initial viability, long-term cellularity and osteoinduction of encapsulated hMSCs in different PA hydrogels were studied in vitro. Temporal progression of osteogenic maturation was assessed by gene expression of key markers. A preliminary animal study demonstrated bone healing capacity of the biphasic PA nanomatrix under physiological conditions using a critical size femoral defect rat model. The combination of RGDS ligand signaling and HA nanoparticles within the biphasic PA nanomatrix hydrogel demonstrated the most effective osteoinduction and comparative bone healing response. Therefore, the biphasic PA nanomatrix establishes a well-organized scaffold with increased similarity to natural bone ECM with the prospect for improved bone tissue regeneration. PMID- 22077995 TI - Effects of intramammary inoculation of Lactobacillus perolens CRL1724 in lactating cows' udders. AB - Bovine mastitis is the most important infectious disease on dairy farms. Conventional antibiotic therapy is often unsatisfactory and alternative treatments are continually under investigation. Lactobacillus (Lb.) perolens CRL 1724 and Lactobacillus plantarum CRL 1716 were previously isolated from milk of dairy cows and selected according to their potential probiotic properties. In the present work the in-vitro capacity of Lactobacillus strains to adhere to bovine teat canal epithelial cells (BTCEC) and to inhibit and co-aggregate 14 mastitis causing pathogens (MCPs) was investigated. The effect of Lb. perolens CRL 1724 after intramammary inoculation in lactating cows was evaluated through determination of clinical signs of mastitis, milk appearance, somatic cell counts and Lb. perolens CRL 1724 recovery from milk. Lb. perolens CRL 1724 was able to inhibit 12 of 14 MCPs (85.7%) in vitro, especially those considered to be major pathogens. In addition, Lb. perolens CRL 1724 co-aggregated with all of them. Lb. plantarum CRL 1716 was able to inhibit 7 of 14 MCPs (50%) in vitro and showed co aggregation ability similar to Lb. perolens CRL 1724. Lb. perolens CRL 1724 showed a higher efficacy of adhesion to BTCEC (values of percentage of adhesion and adhesion index of 75% and 14.4, respectively) than Lb. plantarum CRL 1716 (37% and 7.4, respectively). Lb. perolens CRL 1724 was recovered from all mammary quarters and no clinical signs or teat damage were observed after the inoculation of 106 cfu/ml. The udders presented a normal aspect and there were no changes in the appearance of the milk. The results obtained will serve as the basis for further trials to evaluate the potential of Lb. perolens CRL 1724 to be included in a non-antibiotic formulation for the prevention of bovine mastitis. PMID- 22077994 TI - Developing a community-based genetic nomenclature for anole lizards. AB - BACKGROUND: Comparative studies of amniotes have been hindered by a dearth of reptilian molecular sequences. With the genomic assembly of the green anole, Anolis carolinensis available, non-avian reptilian genes can now be compared to mammalian, avian, and amphibian homologs. Furthermore, with more than 350 extant species in the genus Anolis, anoles are an unparalleled example of tetrapod genetic diversity and divergence. As an important ecological, genetic and now genomic reference, it is imperative to develop a standardized Anolis gene nomenclature alongside associated vocabularies and other useful metrics. RESULTS: Here we report the formation of the Anolis Gene Nomenclature Committee (AGNC) and propose a standardized evolutionary characterization code that will help researchers to define gene orthology and paralogy with tetrapod homologs, provide a system for naming novel genes in Anolis and other reptiles, furnish abbreviations to facilitate comparative studies among the Anolis species and related iguanid squamates, and classify the geographical origins of Anolis subpopulations. CONCLUSIONS: This report has been generated in close consultation with members of the Anolis and genomic research communities, and using public database resources including NCBI and Ensembl. Updates will continue to be regularly posted to new research community websites such as lizardbase. We anticipate that this standardized gene nomenclature will facilitate the accessibility of reptilian sequences for comparative studies among tetrapods and will further serve as a template for other communities in their sequencing and annotation initiatives. PMID- 22077996 TI - The role of cardiovascular magnetic resonance in candidates for Fontan operation: proposal of a new algorithm. AB - BACKGROUND: To propose a new diagnostic algorithm for candidates for Fontan and identify those who can skip cardiac catheterization (CC). METHODS: Forty-four candidates for Fontan (median age 4.8 years, range: 2-29 years) were prospectively evaluated by trans-thoracic echocardiography (TTE), Cardiovascular magnetic resonance (CMR) and CC. Before CC, according to clinical, echo and CMR findings, patients were divided in two groups: Group I comprised 18 patients deemed suitable for Fontan without requiring CC; group II comprised 26 patients indicated for CC either in order to detect more details, or for interventional procedures. RESULTS: In Group I ("CC not required") no unexpected new information affecting surgical planning was provided by CC. Conversely, in Group II new information was provided by CC in three patients (0 vs 11.5%, p = 0.35) and in six an interventional procedure was performed. During CC, minor complications occurred in one patient from Group I and in three from Group II (6 vs 14%, p = 0.7). Radiation Dose-Area product was similar in the two groups (Median 20 Gycm(2), range: 5-40 vs 26.5 Gycm(2), range: 9-270 p = 0.37). All 18 Group I patients and 19 Group II patients underwent a total cavo-pulmonary anastomosis; in the remaining seven group II patients, four were excluded from Fontan; two are awaiting Fontan; one refused the intervention. CONCLUSION: In this paper we propose a new diagnostic algorithm in a pre-Fontan setting. An accurate non invasive evaluation comprising TTE and CMR could select patients who can skip CC. PMID- 22077997 TI - Effects of pelvic suspension of beef carcasses on quality and physical traits of five muscles from four gender-age groups. AB - Pelvic and Achilles suspension methods for beef carcasses were compared for four gender-age groups (24month bulls, 34month bulls, heifers, and cows) and five muscles [M. longissimus dorsi (LD), M. semimembranosus (SM), M. adductor (AD), M. psoas major (PM), and M. gluteus medius (GM)]. Pelvic suspension increased muscle and sarcomere lengths in the SM, LD, GM, and AD muscles. The following effects were significant (p<0.05). Peak force was reduced by pelvic suspension in the LD and GM of bulls-24 and bulls-34, but not heifers and cows. Furthermore, peak forces decreased for the SM after pelvic suspension in bulls-24, bulls-34, and heifers. For the AD, the only decrease in peak force was for bulls-34. Water holding capacity increased and purge in vacuum bags decreased for pelvic suspension of all muscles except the PM. Although the effects of pelvic suspension varied somewhat between gender-age groups and muscles, this method of hanging carcasses merits industrial consideration because it improves muscle yields, tenderness, and reduces variation within muscles. PMID- 22077998 TI - Exposure to a workday environment results in an increase in anterior tilting of the scapula in dental hygienists with greater employment experience. AB - BACKGROUND: Dental hygienists suffer a high incidence of shoulder pathology that seems to increase with job longevity. It has been hypothesized that occupational injuries could be due to local muscle fatigue caused by repetitive low level work and awkward and constrained working postures. In the laboratory, scapular kinematics can be temporarily altered using fatiguing protocols. It is unknown whether or not workday fatigue causes changes to scapular kinematics. The aim of this study was to examine if changes in scapular tilt and rotation occurs after a workday in dental hygienists. METHODS: The pre and post workday scapular kinematics were recorded from dental hygienists using an electromagnetic tracking system. All data were recorded within the place of employment of the dental hygienist. RESULTS: Following the workday, there was significantly more scapular anterior tilt in dental hygienists (P<0.05); however, no changes were found for upward or internal rotation. Greater kinematic differences were found for hygienists with greater job longevity. INTERPRETATION: The increase in scapular anterior tilting could be due to post workday fatigue. Anterior tilting of the scapula may have an influence on the development of subacromial impingement syndrome. Hygienists with greater duration of work experience may be at greater risk for developing shoulder injuries as they have more anterior tilting of the scapula post workday. PMID- 22078000 TI - Ancient founder mutation is responsible for Imerslund-Grasbeck Syndrome among diverse ethnicities. AB - BACKGROUND: Imerslund-Grasbeck syndrome (IGS) was described just over 50 years ago by Olga Imerslund and Ralph Grasbeck and colleagues. IGS is caused by specific malabsorption of cobalamin (Cbl) due to bi-allelic mutations in either the cubilin gene (CUBN) or the human amnionless homolog (AMN). Mutations in the two genes are commonly seen in founder populations or in societies with a high degree of consanguineous marriages. One particular mutation in AMN, c.208-2A>G, causing an out-of-frame loss of exon 4 in the mRNA, is responsible for some 15% of IGS cases globally. We present evidence that this founder mutation causes a substantial percentage of cases among diverse ethnicities and that the mutation is as old as human civilization. METHODS: Partial genotyping indicated a founder event but its presence in diverse peoples of Arabic, Turkish, Jewish, and Hispanic ancestry suggested that the mutation might be recurrent. We therefore studied the flanking sequence spanning 3.5 Mb to elucidate the origin of the haplotype and estimate the age of the mutation using a Bayesian inference method based on observed linkage disequilibrium. RESULTS: The mutation's distribution, the size of the shared haplotype, and estimates of growth rate and carrier frequency indicated that the mutation was a single prehistoric event. Dating back to the ancient Middle East around 11,600 BC, the mutation predates the advent of writing, farming, and the monotheistic religions of the region. CONCLUSIONS: This mutation causes over 50% of the IGS cases among Arabic, Turkish, and Sephardic Jewish families, making it a primary target for genetic screening among diverse IGS cases originating from the Middle East. Thus, rare founder mutations may cause a substantial number of cases, even among diverse ethnicities not usually thought to be related. PMID- 22077999 TI - Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen activated protein kinase pathways. AB - INTRODUCTION: Adiponectin is an adipokine that regulates energy metabolism and insulin sensitivity, but recent studies have pointed also to a role in inflammation and arthritis. The purpose of the present study was to investigate the association and effects of adiponectin on inflammation and cartilage destruction in osteoarthritis (OA). METHODS: Cartilage and blood samples were collected from 35 male OA patients undergoing total knee replacement surgery. Preoperative radiographs were evaluated using Ahlback classification criteria for knee OA. Circulating concentrations of adiponectin and biomarkers of OA, that is, cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase 3 (MMP 3), were measured. Cartilage samples obtained at the time of surgery were cultured ex vivo, and the levels of adiponectin, nitric oxide (NO), IL-6, MMP-1 and MMP-3 were determined in the culture media. In addition, the effects of adiponectin on the production of NO, IL-6, MMP-1 and MMP-3 were studied in cartilage and in primary chondrocyte cultures. RESULTS: Plasma adiponectin levels and adiponectin released from OA cartilage were higher in patients with the radiologically most severe OA (Ahlback grades 4 and 5) than in patients with less severe disease (Ahlback grades 1 to 3). Plasma adiponectin concentrations correlated positively with biomarkers of OA, that is, COMP (r = 0.55, P = 0.001) and MMP-3 (r = 0.34, P = 0.046). Adiponectin was released by OA cartilage ex vivo, and it correlated positively with production of NO (r = 0.43, P = 0.012), IL-6 (r = 0.42, P = 0.018) and MMP-3 (r = 0.34, P = 0.051). Furthermore, adiponectin enhanced production of NO, IL-6, MMP-1 and MMP-3 in OA cartilage and in primary chondrocytes in vitro in a mitogen-activated protein kinase (MAPK) dependent manner. CONCLUSIONS: The findings of this study show that adiponectin is associated with, and possibly mediates, cartilage destruction in OA. PMID- 22078001 TI - Evaluation of thyroid nodules--combined use of (99m)Tc-methylisobutylnitrile scintigraphy and aspiration cytology to assess risk of malignancy and stratify patients for surgical or nonsurgical therapy--a retrospective cohort study. AB - OBJECTIVE: Thyroid nodules are a common clinical problem, and differentiation between benign and malignant nodules is essential. The aim of this study was to evaluate an approach for cold thyroid nodules including (99m)Tc methylisobutylnitrile (MIBI) scintigraphy to assess risk of malignancy and stratify patients for therapy. DESIGN: Retrospective cohort study; 391 patients with at least one cold thyroid nodule were consecutively admitted (between 1 January 2004 and 31 December 2006) and recommended for surgical or nonsurgical therapy. MEASUREMENTS: Thyroid ultrasonography, (99m)Tc-pertechnetate scintigraphy, laboratory tests, fine needle aspiration cytology (FNAC) and MIBI scintigraphy. RESULTS: 57.3% (224/391) had one cold nodule, 17.9% (70/391) had several cold nodules, and 24.8% (97/391) had both cold and hot nodules. MIBI scintigraphy was classified into 'positive' (16.1%, 63/391), 'weakly positive' (19.2%, 75/391) or 'negative' (64.7%, 253/391). FNAC was classified into benign (87.9%, 247/281), nondiagnostic (6.8%, 19/281) or suspicious/malignant (5.3%, 15/281). 127 patients received surgery, revealing malignancy in 13.3% (17/127), predominantly papillary (64.7%, 11/17) and follicular carcinoma (23.5%, 4/17). MIBI scintigraphy was 'positive' (64.7%, 11/17) or 'weakly positive' (23.5%, 4/17) in most patients with malignant findings. FNAC was unavailable in 23.5% (4/17) with malignancy, positive in 38.5% (5/13) and negative in 61.5% (8/13). Among patients undergoing surgery, sensitivity, specificity, negative and positive predictive values for MIBI scintigraphy were 88.2%, 35.5%, 95.1% and 17.4%, for FNAC 38.5%, 90.6%, 90.6% and 38.5%, respectively, and for the combination (MIBI scan + FNAC) 92.3%, 30.6%, 96.3% and 16.9%. Benign MIBI positive nodules were predominantly follicular adenomas (68%, 33/48). CONCLUSION: Evaluation of cold thyroid nodules by MIBI scintigraphy aids therapeutic decisions: MIBI-negative findings support nonsurgical management in about two thirds of patients, while MIBI-positive findings have an increased risk of malignancy, supporting surgical therapy. However, the positive predictive value was low, which requires further research. PMID- 22078003 TI - The clinical results of arthroscopic transtendinous repair of grade III partial articular-sided supraspinatus tendon tears. AB - PURPOSE: The purpose of this study was to evaluate the clinical results of arthroscopic transtendinous repair of deep partial articular-sided rotator cuff tears. METHODS: We retrospectively evaluated the results of 53 patients who underwent arthroscopic transtendinous repair for Ellman grade III articular-sided rotator cuff tears (>50% of the thickness of the rotator cuff). The intact bursal side of the cuff was not detached, and all associated pathology was treated. Fifty patients available for follow-up were evaluated with the American Shoulder and Elbow Surgeons (ASES) questionnaire. RESULTS: American Shoulder and Elbow Surgeons scores improved from a mean of 48.0 to 89.4 (+41.4) (P < .0001). Pain scores on a visual analog scale improved from 5.7 to 1.0 (P < .0001). Ninety eight percent of patients were satisfied with the results of surgery. Results for the 50 patients available for follow-up were excellent in 32 (64%), good in 6 (12%), fair in 6 (12%), and poor in 6 (12%). Articular-sided rotator cuff tears rarely occurred in isolation but were typically found in association with coexisting pathology suggestive of the tears' etiology. Most common were impingement lesions, seen in 94% of patients, and instability lesions such as labral tears, seen in 30% of patients. Associated procedures included acromioplasty in 47, distal clavicle resection in 29, treatment of biceps pathology in 7, and instability repair in 15. One patient sustained a postoperative pulmonary embolism, which represented the only complication. Tears varied in size from 50% to 90% of the thickness of the cuff insertion. Significant differences were identified in the results of Workers' Compensation patients. Preoperative magnetic resonance imaging and magnetic resonance arthrography were accurate in identifying a partial-thickness rotator cuff tear in less than 40% of cases. CONCLUSIONS: Arthroscopic transtendinous repair of partial articular-sided rotator cuff tears is a safe and effective treatment that allows identification of commonly associated pathology and reliable improvement in pain and function. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 22078002 TI - The interest of gait markers in the identification of subgroups among fibromyalgia patients. AB - BACKGROUND: Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia. METHODS: A multicentre, observational open trial enrolled patients with primary FM (44.1 +/- 8.1 y), and matched controls (44.1 +/- 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments. RESULTS: SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ, poor coping and altered affective status. CONCLUSION: Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM. PMID- 22078004 TI - Correlation between anterior cruciate ligament graft obliquity and tibial rotation during dynamic pivoting activities in patients with anatomic anterior cruciate ligament reconstruction: an in vivo examination. AB - PURPOSE: To investigate the effect of coronal- and sagittal-plane anterior cruciate ligament (ACL) graft obliquity on tibial rotation (TR) range of motion (ROM) during dynamic pivoting activities after ACL reconstruction with bone patellar tendon-bone (BPTB) autograft. METHODS: We evaluated 19 ACL-reconstructed patients (mean age, 29 years; age range, 18 to 38 years; mean time interval postoperatively, 19.9 months) and 19 matched control subjects (mean age, 30.6 years; age range, 24 to 37 years) using motion analysis during (1) descending a stairway and pivoting and (2) landing from a jump and pivoting. Magnetic resonance imaging was used to measure the coronal and sagittal ACL graft angle. The dependent variables were TR ROM during pivoting and the side-to-side difference (SSD) in TR ROM between the reconstructed knee and the contralateral intact knee. RESULTS: TR ROM of the ACL-reconstructed knee was significantly increased compared with both the contralateral intact knee and the healthy control knee (P < .05). A significant positive correlation was observed between TR ROM and coronal ACL graft angle (r = 0.727, P = .0006 for descending and pivoting; r = 0.795, P = .0001 for landing and pivoting) as well as between SSD of TR ROM and coronal ACL graft angle (r = 0.789, P < .0001 for descending and pivoting; r = 0.799, P < .0001 for landing and pivoting). No correlation was found with the sagittal ACL graft angle. CONCLUSIONS: After ACL reconstruction with a BPTB graft, patients' knees showed higher TR values than their uninjured knees and the knees of uninjured control volunteers during dynamic pivoting activities. The findings of this study show that TR was better restored in ACL reconstructed patients with a more oblique graft in the coronal plane. A similar relation was not observed for graft orientation in the sagittal plane. Although these data do not imply a cause-and-effect relation between the 2 variables, they may indicate that a more oblique placement of a single BPTB ACL graft in the coronal plane is correlated with better control of TR. LEVEL OF EVIDENCE: Level IV, case series. PMID- 22078005 TI - Anti-angiogenic therapy: concept to clinic. AB - It has been 40 years since Folkman hypothesized the use of anti-angiogenic therapy as a strategy in the treatment of cancer. Since then, vascular endothelial growth factor (VEGF) has been identified as the most potent cytokine to induce angiogenesis and drugs targeting VEGF, principally the humanized monoclonal antibody bevacizumab and the tyrosine kinase inhibitors sunitinib and sorafenib, have proven therapeutic benefit. The initial high expectations of tumor vascular targeting agents, however, have yet to be fulfilled. In unselected patient populations, the benefits of these agents is often marginal, they cause harmful side effects, and drug resistance is quickly established. Biomarkers to identify patients suitable for anti-angiogenic therapy will be key to the future development of these drugs. PMID- 22078006 TI - Tissue-specific LCPUFA accretion in fetal humans. PMID- 22078007 TI - Synthesis and antitubercular activity of novel amino acid derivatives. AB - In this work, 17 new N-acylhydrazone derivatives of amino acids have been evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. The compounds 8b, 8e, 8f, 9a-d, and 10c exhibited an important minimum inhibitory concentration activity between 12.5 and 50 MUg/mL, which can be compared with that of the tuberculostatic drug d-cycloserine (20 MUg/mL). PMID- 22078008 TI - Sex-dimorphism in cardiac nutrigenomics: effect of trans fat and/or monosodium glutamate consumption. AB - BACKGROUND: A paucity of information on biological sex-specific differences in cardiac gene expression in response to diet has prompted this present nutrigenomics investigation. Sexual dimorphism exists in the physiological and transcriptional response to diet, particularly in response to high-fat feeding. Consumption of Trans-fatty acids (TFA) has been linked to substantially increased risk of heart disease, in which sexual dimorphism is apparent, with males suffering a higher disease rate. Impairment of the cardiovascular system has been noted in animals exposed to Monosodium Glutamate (MSG) during the neonatal period, and sexual dimorphism in the growth axis of MSG-treated animals has previously been noted. Processed foods may contain both TFA and MSG. METHODS: We examined physiological differences and changes in gene expression in response to TFA and/or MSG consumption compared to a control diet, in male and female C57BL/6J mice. RESULTS: Heart and % body weight increases were greater in TFA-fed mice, who also exhibited dyslipidemia (P < 0.05). Hearts from MSG-fed females weighed less than males (P < 0.05). 2-factor ANOVA indicated that the TFA diet induced over twice as many cardiac differentially expressed genes (DEGs) in males compared to females (P < 0.001); and 4 times as many male DEGs were downregulated including Gata4, Mef2d and Srebf2. Enrichment of functional Gene Ontology (GO) categories were related to transcription, phosphorylation and anatomic structure (P < 0.01). A number of genes were upregulated in males and downregulated in females, including pro-apoptotic histone deacetylase-2 (HDAC2). Sexual dimorphism was also observed in cardiac transcription from MSG-fed animals, with both sexes upregulating approximately 100 DEGs exhibiting sex-specific differences in GO categories. A comparison of cardiac gene expression between all diet combinations together identified a subset of 111 DEGs significant only in males, 64 DEGs significant in females only, and 74 transcripts identified as differentially expressed in response to dietary manipulation in both sexes. CONCLUSION: Our model identified major changes in the cardiac transcriptional profile of TFA and/or MSG-fed mice compared to controls, which was reflected by significant differences in the physiological profile within the 4 diet groups. Identification of sexual dimorphism in cardiac transcription may provide the basis for sex specific medicine in the future. PMID- 22078009 TI - Involvement of viral factors with head and neck cancers. AB - The incidence of head and neck cancer remains high and is associated with many deaths in both Western and Asian countries. Common risk factors in head and neck carcinoma are smoking and alcohol abuse, however, in an increasing proportion of cases, no significant smoking or drinking history has been reported. The infectious nature of oncogenic viruses sets them apart from other carcinogenic agents. As such, a thorough study of both the pathogenesis of viral infection and the host response is crucial to a full understanding of the resulting cancers. Such an understanding, in turn, has increased our knowledge of cellular pathways involved in growth and differentiation and neoplasia as a whole. Even though human oncogenic viruses belong to different virus families and utilize diverse strategies to contribute to cancer development, they share many common features. Viruses linked to cancers in humans are the human papilloma viruses, Epstein-Barr virus, hepatitis C virus and human herpesvirus-8. The potential role and involvement of these viruses in head and neck cancers along with brief description of vaccine development is provided. PMID- 22078010 TI - Oral oocyst-induced mouse model of toxoplasmosis: effect of infection with Toxoplasma gondii strains of different genotypes, dose, and mouse strains (transgenic, out-bred, in-bred) on pathogenesis and mortality. AB - Humans and other hosts acquire Toxoplasma gondii infection by ingesting tissue cysts in undercooked meat, or by food or drink contaminated with oocysts. Currently, there is no vaccine to prevent clinical disease due this parasite in humans, although, various T. gondii vaccine candidates are being developed. Mice are generally used to test the protective efficacy of vaccines because they are susceptible, reagents are available to measure immune parameters in mice, and they are easily managed in the laboratory. In the present study, pathogenesis of toxoplasmosis was studied in mice of different strains, including Human Leukocyte Antigen (HLA) transgenic mice infected with different doses of T. gondii strains of different genotypes derived from several countries. Based on many experiments, the decreasing order of infectivity and pathogenicity of oocysts was: C57BL/6 background interferon gamma gene knock out (KO), HLA-A*1101, HLA-A*0201, HLA B*0702, Swiss Webster, C57/black, and BALB/c. Mice fed as few as 1 oocyst of Type I and several atypical strains died of acute toxoplasmosis within 21 days p.i. Some Type II, and III strains were less virulent. The model developed herein should prove to be extremely useful for testing vaccines because it is possible to accurately quantitate a challenge inoculum, test the response to different strains of T. gondii using the same preparations of oocysts which are stable for up to a year, and to have highly reproducible responses to the infection. PMID- 22078011 TI - Minimal residual disease and circulating tumor cells in breast cancer. AB - Tumor cell dissemination in bone marrow or other organs is thought to represent an important step in the metastatic process. The detection of bone marrow disseminated tumor cells is associated with worse outcome in early breast cancer. Moreover, the detection of peripheral blood circulating tumor cells is an adverse prognostic factor in metastatic breast cancer, and emerging data suggest that this is also true for early disease. Beyond enumeration, the characterization of these cells has the potential to improve risk assessment, treatment selection and monitoring, and the development of novel therapeutic agents, and to advance our understanding of the biology of metastasis. PMID- 22078012 TI - A rare bladder cancer--small cell carcinoma: review and update. AB - Small cell carcinoma of the bladder (SCCB) is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC). Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease (< or = cT1-4aN0M0) should be managed with multimodal therapy associating chemotherapy, surgery and/or radiotherapy. Neoadjuvant chemotherapy using four chemotherapy cycles followed by radical cystectomy is the most effective therapeutic sequence. Patients with unresectable disease (> or = cT4bN+M+) should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients). The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB. PMID- 22078016 TI - Clinical practice guideline for abnormal uterine bleeding: hysterectomy versus alternative therapy. AB - STUDY OBJECTIVE: To develop recommendations in selecting treatments for abnormal uterine bleeding (AUB). DESIGN: Clinical practice guidelines. SETTING: Randomized clinical trials compared bleeding, quality of life, pain, sexual health, satisfaction, the need for subsequent surgery, and adverse events between hysterectomy and less-invasive treatment options. PATIENTS: Women with AUB, predominantly from ovulatory disorders and endometrial causes. INTERVENTIONS: On the basis of findings from a systematic review, clinical practice guidelines were developed. Rating the quality of evidence and the strength of recommendations followed the Grades for Recommendation Assessment, Development, and Evaluation system. MEASUREMENTS AND MAIN RESULTS: This paper identified few high-quality studies that directly compared uterus-preserving treatments (endometrial ablation, levonorgestrel intrauterine system and systemically administered medications) with hysterectomy. The evidence from these randomized clinical trials demonstrated that there are trade-offs between hysterectomy and uterus preserving treatments in terms of efficacy and adverse events. CONCLUSION: Selecting an appropriate treatment for AUB requires identifying a woman's most burdensome symptoms and incorporating her values and preferences when weighing the relative benefits and harms of hysterectomy versus other treatment options. PMID- 22078015 TI - A systematic review comparing hysterectomy with less-invasive treatments for abnormal uterine bleeding. AB - STUDY OBJECTIVE: To compare hysterectomy with less-invasive alternatives for abnormal uterine bleeding (AUB) in 7 clinically important domains. DESIGN: Systematic review. SETTING: Randomized clinical trials comparing bleeding, quality of life, pain, sexual health, satisfaction, need for subsequent surgery, and adverse events between hysterectomy and less-invasive treatment options. PATIENTS: Women with AUB, predominantly from ovulatory disorders and endometrial causes. INTERVENTIONS: Systematic review of the literature (from inception to January 2011) comparing hysterectomy with alternatives for AUB treatment. Eligible trials were extracted into standardized forms. Trials were graded with a predefined 3-level rating, and the strengths of evidence for each outcome were evaluated with the Grades for Recommendation, Assessment, Development and Evaluation system. MEASUREMENTS AND MAIN RESULTS: Nine randomized clinical trials (18 articles) were eligible. Endometrial ablation, levonorgestrel intrauterine system, and medications were associated with lower risk of adverse events but higher risk of additional treatments than hysterectomy. Compared to ablation, hysterectomy had superior long-term pain and bleeding control. Compared with the levonorgestrel intrauterine system, hysterectomy had superior control of bleeding. No other differences between treatments were found. CONCLUSION: Less invasive treatment options for AUB result in improvement in quality of life but carry significant risk of retreatment caused by unsatisfactory results. Although hysterectomy is the most effective treatment for AUB, it carries the highest risk for adverse events. PMID- 22078017 TI - Editorial: economies of scale: the future of ageing. PMID- 22078018 TI - Guest editorial: beyond knowledge translation, towards the 'public scholar'. PMID- 22078020 TI - Best practice in fall prevention: roles of informal caregivers, health care providers and the community. AB - Falls are an important public health problem for older adults, resulting in significant morbidity and mortality, as well as healthcare costs. Evidence supports the assessment of older adults' fall risks and implementation of interventions to reduce these risks. Older adults are the key stakeholder in preventing falls, but need the support of their informal caregivers, healthcare providers, and community groups. This article addresses the roles of these additional stakeholders in providing and supporting best practices in fall prevention. Together these stakeholders can assist older adults in self management of fall prevention, based on the preferences of the individual, local resources, and available programmes and healthcare services. PMID- 22078019 TI - Older people's perspectives on fall risk and fall prevention programs: a literature review. AB - Despite evidence supporting fall prevention methods, fall-related injury and death rates continue to rise. Understanding older people's views on fall risk and prevention will help nurses and other health professionals in the design of fall prevention strategies that will broaden their scope, reach and adoption. This literature review synthesised 19 qualitative and quantitative studies examining older people's perspectives about fall risk and prevention using a social ecological framework. Three themes emerged about fall risk; fearing vulnerability, maintaining autonomy and independence and interpreting risk. Four themes emerged about fall prevention programs: influence of participant and program characteristics, need for personal relevance and preference, maintaining autonomy and independence and increased support for and access to programs. Implications for practice include individual, interpersonal, organizational and community level considerations for improving fall prevention efforts. PMID- 22078021 TI - Falls prevention and support: translating research, integrating services and promoting the contribution of service users for quality and innovative programmes of care. AB - Falls are a significant threat to the safety, health and independence of older citizens. Despite the substantial evidence that is available around effective falls prevention programmes and interventions, their translation into falls reduction programmes and policies has yet to be fully realised. While hip fracture rates are decreasing, the number and incidence of fall-related hospital admissions among older people continue to rise. Given the demographic trends that highlight increasing numbers of older people in the UK, which is broadly reflected internationally, there is a financial and social imperative to minimise the rate of falls and associated injuries. Falling is closely aligned to growing older (Slips, Trips and Falls Update: From Acute and Community Hospitals and Mental Health Units in England and Wales, Department of Health, HMSO, London, 2010). According to the World Health Organization, around 30% of older people aged over 65 and 50% of those over 80 will fall each year (Falls Fact Sheet Number 344, WHO, Geneva, 2010). Falls happen as a result of many reasons and can have harmful consequences, including loss of mobility and independence, confidence and in many cases even death (Cochrane Database Syst Rev 15, 2009, 146; Slips, Trips and Falls Update: From Acute and Community Hospitals and Mental Health Units in England and Wales, Department of Health, HMSO, London, 2010; Falling Standards, Broken Promises: Report of the National Audit of Falls and Bone Health in Older People 2010, Health Care Quality Improvement Partnership, London, 2011). What is neither fair nor correct is the common belief by old and young alike that falls are just another inconvenience to put up with. The available evidence justifiably supports the view that well-organised services, based upon national standards and expert guidance, can prevent future falls among older people and reduce death and disability from fractures. This paper will draw from the UK, as an exemplar for policy and practice, to discuss the strategic direction of falls prevention programmes for older people and the partnerships that need to exist between researchers, service providers and users of services to translate evidence to the clinical setting. Second, it will propose some mechanisms for disseminating evidence to healthcare professionals and other stakeholders, to improve the quality and capacity of the clinical workforce. PMID- 22078022 TI - Nutritional supplementation for hip fracture aftercare in older people. PMID- 22078024 TI - Annealing of gold nanostructures sputtered on polytetrafluoroethylene. AB - Gold nanolayers sputtered on polytetrafluoroethylene (PTFE) surface and their changes induced by post-deposition annealing at 100 degrees C to 300 degrees C are studied. Changes in surface morphology and roughness are examined by atomic force microscopy, electrical sheet resistance by two point technique, zeta potential by electrokinetic analysis and chemical composition by X-ray photoelectron spectroscopy (XPS) in dependence on the gold layer thickness. Transition from discontinuous to continuous gold coverage takes place at the layer thicknesses 10 to 15 nm and this threshold remains practically unchanged after the annealing at the temperatures below 200 degrees C. The annealing at 300 degrees C, however, leads to significant rearrangement of the gold layer and the transition threshold increases to 70 nm. Significant carbon contamination and the presence of oxidized structures on gold-coated samples are observed in XPS spectra. Gold coating leads to a decrease in the sample surface roughness. Annealing at 300 degrees C of pristine PTFE and gold-coated PTFE results in significant increase of the sample surface roughness. PMID- 22078023 TI - Classic Kaposi's sarcoma in Morocco: clinico-epidemiological study at the National Institute of Oncology. AB - BACKGROUND: Classic Kaposi's sarcoma (CKS) is a rare disease likely associated with human herpes virus 8 (HHV-8) infection, and occurs predominantly in Jewish, Mediterranean and middle eastern men. There is a dearth of data in Moroccan patients with CKS regarding epidemiology, clinical characteristics and outcomes. This report examines a cohort of patients with CKS evaluated at the national institute of oncology over 11-year period. METHODS: A retrospective analysis of patients referred to the national institute of oncology with classical Kaposi sarcoma, between January 1998 and February 2008, was performed. Reviewed information included demographics, clinical and pathological staging, death or last follow-up. RESULTS: During the study period, 56 patients with a diagnosis of CKS have been referred to our hospital. There were 11 (19.7%) females and 45 (80.3%) males (male-to-female ratio: 4:1). Mean age at diagnosis was 61.7 +/- 15 (range: 15-86 years). Nodules and/or plaques were the most frequent type of lesion. The most common location was the lower limbs, particularly the distal lower extremity (90%). In addition to skin involvement, visceral spread was evident in 9 cases. The most common visceral involvement sites were lymph nodes (44%), lung (22%), and gastrointestinal tract (22%). Associated lymphoedema was seen in 24 (42%) of the patients. There were 18 stage I patients (32.14%), 8: stage II (14.28%), 21 stage III (37.5%) and 9 stage IV (16.07%). A second primary malignancy was diagnosed in 6 cases (10.7%), none of the reticuloendothelial system. With a median follow-up of 45 months, 38 (67.8) patients are alive, of whom 25 (65.78%) patients with stable disease, five with progressive disease currently under systemic chemotherapy and 8 (21.05%) are alive and free of disease, over a mean interval of 5 years. CONCLUSION: This is the largest reported series in our context. In Morocco, CKS exhibits some special characteristics including a disseminated skin disease at diagnosis especially in men, a more common visceral or lymph node involvement and a less frequent association with second malignancies. PMID- 22078025 TI - An assessment of the use of drug and non-drug interventions in the treatment of Ichthyophthirius multifiliis Fouquet, 1876, a protozoan parasite of freshwater fish. AB - Infection by the ciliate protozoan Ichthyophthirius multifiliis Fouquet, 1876 causes significant economic losses in freshwater aquaculture worldwide. Following the ban on the use of malachite green for treating food fish, there has been extensive research aimed at identifying suitable replacements. In this paper we critically assess drug and non-drug interventions, which have been tested for use or have been employed against this parasite and evaluate possibilities for their application in farm systems. Current treatments include the administration of formaldehyde, sodium chloride (salt), copper sulphate and potassium permanganate. However, purportedly more environmentally friendly drugs such as humic acid, potassium ferrate (VI), bronopol and the peracetic acid-based products have recently been tested and represent promising alternatives. Further investigation, is required to optimize the treatments and to establish precise protocols in order to minimize the quantity of drug employed whilst ensuring the most efficacious performance. At the same time, there needs to be a greater emphasis placed on the non-drug aspects of management strategies, including the use of non chemical interventions focusing on the removal of free-swimming stages and tomocysts of I. multifiliis from farm culture systems. Use of such strategies provides the hope of more environmentally friendly alternatives for the control of I. multifiliis infections. PMID- 22078026 TI - The microenvironment in breast cancer progression: biology and implications for treatment. AB - Breast cancer comprises a heterogeneous group of malignancies derived from the ductal epithelium. The microenvironment of these cancers is now recognized as a critical participant in tumor progression and therapeutic responses. Recent data demonstrate significant gene expression and epigenetic alterations in cells composing the microenvironment during disease progression, which can be explored as biomarkers and targets for therapy. Indeed, gene expression signatures derived from tumor stroma have been linked to clinical outcomes. There is increasing interest in translating our current understanding of the tumor microenvironment to the development of novel therapies. PMID- 22078028 TI - A multi-season national estimate of adult influenza vaccination by U.S. office based pediatricians, 2006-2011. AB - There is no national estimate of adult influenza vaccination by U.S. office-based pediatricians. De-identified patient-level data from an electronic healthcare claims database submitted to private and public insurers were analyzed for pediatric offices from the 2006-2007 through 2010-2011 seasons. An average of 321,000 (range: 225,000-434,000) influenza vaccinations per year were estimated to be administered to adults; 52%, 22%, and 26% were given to adults 19-49, 50 64, and >=65 years of age, respectively. Consistent with the 2010 changes to national guidelines, recommending influenza vaccination of all individuals 6 months of age and older, pediatricians appear to be providing an increasing proportion of adult vaccinations against influenza to adults 19-49 years of age (probably parents of their pediatric patients). PMID- 22078027 TI - Transcriptome analysis of orange-spotted grouper (Epinephelus coioides) spleen in response to Singapore grouper iridovirus. AB - BACKGROUND: Orange-spotted grouper (Epinephelus coioides) is an economically important marine fish cultured in China and Southeast Asian countries. The emergence of infectious viral diseases, including iridovirus and betanodavirus, have severely affected food products based on this species, causing heavy economic losses. Limited available information on the genomics of E. coioides has hampered the understanding of the molecular mechanisms that underlie host-virus interactions. In this study, we used a 454 pyrosequencing method to investigate differentially-expressed genes in the spleen of the E. coioides infected with Singapore grouper iridovirus (SGIV). RESULTS: Using 454 pyrosequencing, we obtained abundant high-quality ESTs from two spleen-complementary DNA libraries which were constructed from SGIV-infected (V) and PBS-injected fish (used as a control: C). A total of 407,027 and 421,141 ESTs were produced in control and SGIV infected libraries, respectively. Among the assembled ESTs, 9,616 (C) and 10,426 (V) ESTs were successfully matched against known genes in the NCBI non redundant (nr) database with a cut-off E-value above 10-5. Gene ontology (GO) analysis indicated that "cell part", "cellular process" and "binding" represented the largest category. Among the 25 clusters of orthologous group (COG) categories, the cluster for "translation, ribosomal structure and biogenesis" represented the largest group in the control (185 ESTs) and infected (172 ESTs) libraries. Further KEGG analysis revealed that pathways, including cellular metabolism and intracellular immune signaling, existed in the control and infected libraries. Comparative expression analysis indicated that certain genes associated with mitogen-activated protein kinase (MAPK), chemokine, toll-like receptor and RIG-I signaling pathway were alternated in response to SGIV infection. Moreover, changes in the pattern of gene expression were validated by qRT-PCR, including cytokines, cytokine receptors, and transcription factors, apoptosis-associated genes, and interferon related genes. CONCLUSION: This study provided abundant ESTs that could contribute greatly to disclosing novel genes in marine fish. Furthermore, the alterations of predicted gene expression patterns reflected possible responses of these fish to the virus infection. Taken together, our data not only provided new information for identification of novel genes from marine vertebrates, but also shed new light on the understanding of defense mechanisms of marine fish to viral pathogens. PMID- 22078029 TI - The logic layout of the TOL network of Pseudomonas putida pWW0 plasmid stems from a metabolic amplifier motif (MAM) that optimizes biodegradation of m-xylene. AB - BACKGROUND: The genetic network of the TOL plasmid pWW0 of the soil bacterium Pseudomonas putida mt-2 for catabolism of m-xylene is an archetypal model for environmental biodegradation of aromatic pollutants. Although nearly every metabolic and transcriptional component of this regulatory system is known to an extraordinary molecular detail, the complexity of its architecture is still perplexing. To gain an insight into the inner layout of this network a logic model of the TOL system was implemented, simulated and experimentally validated. This analysis made sense of the specific regulatory topology out on the basis of an unprecedented network motif around which the entire genetic circuit for m xylene catabolism gravitates. RESULTS: The most salient feature of the whole TOL regulatory network is the control exerted by two distinct but still intertwined regulators (XylR and XylS) on expression of two separated catabolic operons (upper and lower) for catabolism of m-xylene. Following model reduction, a minimal modular circuit composed by five basic variables appeared to suffice for fully describing the operation of the entire system. In silico simulation of the effect of various perturbations were compared with experimental data in which specific portions of the network were activated with selected inducers: m-xylene, o-xylene, 3-methylbenzylalcohol and 3-methylbenzoate. The results accredited the ability of the model to faithfully describe network dynamics. This analysis revealed that the entire regulatory structure of the TOL system enables the action an unprecedented metabolic amplifier motif (MAM). This motif synchronizes expression of the upper and lower portions of a very long metabolic system when cells face the head pathway substrate, m-xylene. CONCLUSION: Logic modeling of the TOL circuit accounted for the intricate regulatory topology of this otherwise simple metabolic device. The found MAM appears to ensure a simultaneous expression of the upper and lower segments of the m-xylene catabolic route that would be difficult to bring about with a standard substrate-responsive single promoter. Furthermore, it is plausible that the MAM helps to avoid biochemical conflicts between competing plasmid-encoded and chromosomally-encoded pathways in this bacterium. PMID- 22078031 TI - [Ethics and medical techniques: a transcultural approach]. PMID- 22078030 TI - Inhibitory effect of aqueous Dandelion extract on HIV-1 replication and reverse transcriptase activity. AB - BACKGROUND: Acquired immunodeficiency syndrome (AIDS), which is caused by the human immunodeficiency virus (HIV), is an immunosuppressive disease that results in life-threatening opportunistic infections. The general problems in current therapy include the constant emergence of drug-resistant HIV strains, adverse side effects and the unavailability of treatments in developing countries. Natural products from herbs with the abilities to inhibit HIV-1 life cycle at different stages, have served as excellent sources of new anti-HIV-1 drugs. In this study, we aimed to investigate the anti-HIV-1 activity of aqueous dandelion extract. METHODS: The pseudotyped HIV-1 virus has been utilized to explore the anti-HIV-1 activity of dandelion, the level of HIV-1 replication was assessed by the percentage of GFP-positive cells. The inhibitory effect of the dandelion extract on reverse transcriptase activity was assessed by the reverse transcriptase assay kit. RESULTS: Compared to control values obtained from cells infected without treatment, the level of HIV-1 replication and reverse transcriptase activity were decreased in a dose-dependent manner. The data suggest that dandelion extract has a potent inhibitory activity against HIV-1 replication and reverse transcriptase activity. The identification of HIV-1 antiviral compounds from Taraxacum officinale should be pursued. CONCLUSIONS: The dandelion extract showed strong activity against HIV-1 RT and inhibited both the HIV-1 vector and the hybrid-MoMuLV/MoMuSV retrovirus replication. These findings provide additional support for the potential therapeutic efficacy of Taraxacum officinale. Extracts from this plant may be regarded as another starting point for the development of an antiretroviral therapy with fewer side effects. PMID- 22078032 TI - [Iatrogenic Kaposi's disease in Morocco in a non-transplant context]. AB - BACKGROUND: Kaposi's disease (KD) is a multifocal disease affecting the skin and viscera. KD can occur in an endemic setting: it may be associated with human immunodeficiency virus (HIV) or it may occur as a complication of immunosuppression, particularly of iatrogenic origin in transplant patients. The purpose of this study is to describe the epidemiological, clinical and therapeutic profile and the course of iatrogenic KD in Morocco in a setting not involving organ transplantation. PATIENTS AND METHODS: A retrospective study conducted at the dermatology department of the Ibn Sina hospital centre in Rabat, Morocco, covering a 21-year period and including 14 patients presenting histologically confirmed iatrogenic KD. RESULTS: Eight men and six women were included with a mean age of 56 years. All patients received corticosteroids, in combination with cyclophosphamide in three cases and with azathioprine in one case. The mean time to onset of lesions after the start of treatment was 16.5 months. The presentation in all cases was cutaneous. Impaired mucosal membrane was seen in 35.7% of patients, with visceral involvement being seen in only one patient. HIV serology tests were negative in all patients but HHV8 serology tests were positive in 78.5% of patients. Treatment consisted primarily of reduction or withdrawal of the immunosuppressant. The outcome was favourable in the majority of cases. CONCLUSION: In Morocco, KD is a rare but not exceptional complication of immunosuppressant therapy, particularly corticosteroids. The disease presented as a skin disorder in all of our patients, thus emphasising the value of regular follow-up and routine dermatological examination of patients on immunosuppressant therapy, and suggesting the value of screening for HHV8 infection before initiating such therapy. PMID- 22078033 TI - [Multiple cutaneous osteomas of the face in a setting of chronic acne]. AB - BACKGROUND: Multiple cutaneous osteomas are a rare complication of chronic inflammatory acne that often goes unrecognized. We report a case concerning a 35 year-old woman. PATIENTS AND METHODS: A 35-year-old woman had been treated for acne since the age of 22 years, as part of which she received two courses of oral isotretinoin. We noted the secondary appearance of several microcysts on the face for which the excision was very difficult. Curiously, these small formations did not contain keratin but were very callous. Histological examination revealed foci of osseous metaplasia, probably of postinflammatory origin. Treatment consisted solely of excision of the lesions. DISCUSSION: Osteoma cutis comprises two distinct groups (primary and secondary). In our case, there were multiple cutaneous osteomas of the face resulting from chronic acne. The differential diagnosis was idiopathic miliary osteomatosis of the face, but this was ruled out by the young age of the patient, the improvement of the acneiform lesions under isotretinoin (confirming the initial diagnosis of acne) and the subsequent appearance of microcysts. Although there are as yet no codified treatments, excision appears to yield good results. PMID- 22078034 TI - [Anti-p200 pemphigoid: a spectacular response to dapsone]. AB - BACKGROUND: Types of subepidermal autoimmune bullous dermatosis (AIBD) are classified by anatomoclinical picture and target antigen. A new entity has recently been identified: anti-p200 pemphigoid. PATIENTS AND METHODS: An 82-year old man consulted for a profuse pruritic bullous eruption refractory to the standard treatments for bullous pemphigoid (BP). Direct immunofluorescence examination of a skin biopsy revealed linear deposits of IgG and of C3 at the dermal-epidermal junction, but Elisa screening for circulating anti-BP180 and anti-BP230 antibodies was negative. Indirect immunofluorescence (IIF) testing of cleaved skin revealed a deposit of IgG4 antibodies on the dermal side. Immunoblotting was negative for a dermal extract but showed an antibody directed against a 200-kD epidermal antigen. A diagnosis of anti-p200 pemphigoid was eventually made and the patient was successfully treated with dapsone. DISCUSSION: The diagnosis of anti-p200 pemphigoid was made in this case in spite of discrepancy between the IIF and immunoblotting results, and despite the fact that the target antigen in this disease is considered as being restricted to dermal sites. Anti-p200 pemphigoid usually begins in the second part of life and differs from standard bullous pemphigoid in terms of more frequent mucous membrane and cephalic involvement, as well as a greater degree of miliary scarring. This disease appears more prominent in males and is associated with psoriasis in around one third of cases. Autoantibodies recognize laminin gamma-1, an extra-desmosomal protein that contributes to dermal-epidermal adhesion. CONCLUSION: This recently described disease as probably under-diagnosed in France. It should be considered in atypical presentations of bullous disease. Diagnosis is confirmed by immunoblotting detection of autoantibodies directed against a 200-kD antigen normally present in the extract. Dapsone appears to be the most effective treatment. PMID- 22078035 TI - [Associated Langerhans cell histiocytosis and Erdheim-Chester disease]. AB - BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis with multiple organ involvement affecting middle-aged adults. A case of ECD associated with Langerhans cell histiocytosis (LCH) is reported herein. CASE REPORT: A 75-year-old woman presented maculopapular skin lesions on her trunk, associated with constrictive pericarditis and pleurisy present for 1 year. The skin biopsy militated in favour of LCH since it revealed a histiocytic infiltrate with a positive CD1a marker at immunohistochemistry (IHC). The association with ECD was diagnosed on the basis of pericarditis, periaortitis, pleurisy, pulmonary involvement and retroperitoneal fibrosis. The patient was treated with interferon-alpha2a with good initial results, but died from septic shock a year and a half later, a few months after discontinuing interferon due to poor tolerability. DISCUSSION: The clinical, radiographic and histological arguments in favour of ECD clearly differ from those for LCH. However, as already reported, the two illnesses may be associated, thus underlining the possible existence of a link between these two histiocytic proliferations emanating from the same medullary precursor. Two hypotheses have been advanced in an attempt to explain this association: the first involves a stimulus that might lead to independent proliferation of the two cell lines while the second suggests the existence of a transformation pathway from one form of proliferation to the other. CONCLUSION: Screening for associated ECD should be routinely performed in patients presenting LCH with signs evocative of ECD. PMID- 22078036 TI - [Unilateral purpura of a limb revealing a periprosthetic abscess in an HIV infected patient]. AB - BACKGROUND: Many diagnoses may be evoked in the presence of purpuric lesions of the lower limbs in HIV-positive patients. We report here on a Staphylococcus aureus abscess around a vascular prosthesis revealed by unilateral purpuric lesions. PATIENTS AND METHODS: A 43-year-old HIV-positive man was referred to us with febrile purpura of the left lower limb. His past medical history included a crossover iliofemoral arterial bypass. Clinical examination revealed fever and infiltrated purpuric lesions on the left ankle associated with cyanotic left toes. A skin biopsy showed leucocytoclastic vasculitis. A voluminous right iliac abscess was demonstrated by abdominal and pelvic CT scans. S. aureus was isolated from the skin biopsy, two blood cultures and the periprosthetic abscess. The abscess was drained without replacing the prosthesis and antibiotic therapy consisting of oxacillin was given for 6 months, resulting in complete healing. DISCUSSION: Vascular prosthetic infections are rare events that can occur early or late after surgery. S. aureus is usually the causative infectious agent. Clinical signs are non-specific and include purpuric lesions, which rarely reveal these infections. The organism may generally be isolated from prosthetic materials and blood cultures. CT scan is the recommended test to visualize prosthetic impairment. Treatment comprises prolonged antibiotic therapy adapted in accordance with the bacterial antibiogram, along with surgical debridement and, preferably, prosthetic replacement. CONCLUSION: This case report describes a unilateral purpura revealing a periprosthetic abscess. Dermatologists must be aware of this sign as a potential indicator of prosthetic infection. PMID- 22078037 TI - [Pityriasis rubra pilaris after vaccination]. AB - BACKGROUND: Pityriasis rubra pilaris (PRP) following vaccination is rarely described in the literature. We report a case of PRP occurring two weeks after measles-mumps-rubella (MMR) vaccination. CASE REPORT: A 17-month-old infant was referred for a rash appearing two weeks previously. The child was presenting diffuse erythematous scaly exanthema with follicular papules and orange palmoplantar keratoderma. The clinical features were highly evocative of PRP. The histology was non-specific, displaying epidermal acanthosis with a regular and thick parakeratosis, and without any impairment of the follicular infundibulum. An MMR vaccination had been given two weeks before onset of the rash. Treatment with topical corticosteroids and emollients proved effective. DISCUSSION: Post vaccinal PRP is rarely described in the literature. We report only the 3rd case. The first case concerned a 32-year-old woman presenting two episodes of PRP 10 days after diphtheria-tetanus-polio vaccination. The second case concerned a 47 year-old woman presenting PRP 18 days after anti-influenza vaccination and requiring treatment with acitretin. No cases have been described with MMR. These three vaccines (DTP, Tetragrip and ROR) have no shared pharmacological constituents, and the trigger mechanism could be immunological or parainfectious. CONCLUSION: Questioning about recent vaccination during history taking appears necessary to assess the importance of this trigger factor as well as the mechanism responsible for the onset of PRP. PMID- 22078038 TI - [Groove sign in cat-scratch disease]. PMID- 22078039 TI - [Aggressive universal calcinosis complicating dermatomyositis]. PMID- 22078040 TI - [Digital ulcers in systemic scleroderma]. PMID- 22078041 TI - [Cultural diversity: ethical issues for the dermatologist]. PMID- 22078042 TI - [Histopathology of leprosy]. PMID- 22078043 TI - [Histopathological diagnosis of inherited epidermolysis bullosa]. PMID- 22078044 TI - [Of genes and nails]. PMID- 22078045 TI - [Multiple self-healing squamous epithelioma, or Ferguson-Smith disease: demonstration of mutations in the TGFbeta-receptor]. PMID- 22078046 TI - [A case of bullous lupus in black skin]. PMID- 22078047 TI - [Molluscum contagiosum on the buttocks of neonates]. PMID- 22078048 TI - [Giant cutaneous xanthomas revealing homozygous familial hypercholesterolaemia]. PMID- 22078049 TI - [Linear porokeratosis]. PMID- 22078050 TI - [Ballroom dancing and consort allergic contact dermatitis]. PMID- 22078051 TI - [Careful: skins cancers and voriconazole]. PMID- 22078052 TI - Transient osteoporosis of the hip in pregnancy resulting in bilateral fracture of the neck of the femur. PMID- 22078053 TI - The effect of time of day on unscheduled cesarean delivery and perinatal outcome. PMID- 22078054 TI - Initiation of prenatal genetic diagnosis of chromosomal anomalies in Cameroon. PMID- 22078055 TI - Sociological approaches to the study of drug use and drug policy. PMID- 22078056 TI - A case of lymphomatoid gastropathy: An indolent CD56-positive atypical gastric lymphoid proliferation, mimicking aggressive NK/T cell lymphomas. AB - Lymphomatoid gastropathy (LyGa) is a new evolving pathological entity that has been introduced recently. It is designated to describe CD56-positive atypical gastric lymphoid proliferation, mimicking NK/T cell lymphomas, that shows an indolent clinical course with spontaneous regression. We here present our experience with one new case diagnosed and treated in our hospital. An annual upper endoscopic check-up of a 50-year-old male with an unremarkable past history revealed a small reddish lesion on the posterior wall of the gastric angle. Endoscopic biopsy showed atypical cells of NK-cell lineage expressing CD56, CD16, CD3, perforin, and TIA-1, but not CD4, CD5, and CD8. Epstein-Barr virus encoded RNA was negative. The lesion regressed spontaneously after one month without treatment, but recurred two years later in a different site of the stomach with spontaneous regression again one month later. The recurrence of lymphomatoid gastropathy is very rare and should be diagnosed carefully to distinguish it from the aggressive lymphoma. PMID- 22078057 TI - Spectrum of cardiac tumors excluding myxoma: Experience of a tertiary center with review of the literature. AB - The aim of this study was to determine the histological spectrum of operated cardiac tumors, excluding myxoma, at a tertiary center in India. Between 1995 and 2010, we encountered 188 cases of operated cardiac tumors that had been subjected to histopathological examination. Morphological characterization was done by light microscopy along with histochemical stains. Immunohistochemistry using a panel of antibodies, i.e., vimentin, desmin, myogenin, smooth muscle actin (SMA), epithelial membrane antigen (EMA), cytokeratins, factor VIII-related antigen, S100-protein, synaptophysin, chromogranin, Bcl2, MIB-1, leukocyte common antigen (LCA), CD 3, CD20, CD34, and CD 99 (MIC-2) was performed wherever applicable. Out of the 188 cases, 184 were primary cardiac tumors, including 170 cases of benign cardiac tumors. Among the benign tumors, myxomas were the most frequent ones (168 cases), followed by fibroma (2 cases). Primary malignancy was diagnosed in 14 cases, including undifferentiated sarcomas, primitive neuroectodermal tumor, rhabdomyosarcoma non-Hodgkin lymphoma, angiosarcoma, synovial sarcoma, and leiomyosarcoma. Metastatic (secondary) tumors were seen in four cases, including one each of adenocarcinoma, choriocarcinoma, renal cell carcinoma, and alveolar soft part sarcoma. Hence, out of the total of 188 cases, 20 were non-myxoma cardiac tumors (NMCTs), including 2 benign tumors, 14 malignant tumors, and 4 metastatic tumors. In our series, the majority of cardiac tumors were primary in nature. The malignant primary tumors outnumbered benign ones, excluding myxomas, and the most common malignant histology was undifferentiated sarcoma, as opposed to the literature. PMID- 22078058 TI - Association of family history of ESRD, prevalent albuminuria, and reduced GFR with incident ESRD. AB - BACKGROUND: The contribution of albuminuria to the increased risk of incident end stage renal disease (ESRD) in individuals with a family history of ESRD has not been well studied. STUDY DESIGN: Prospective cohort study. STUDY SETTING & PARTICIPANTS: We analyzed data for family history of ESRD collected from 19,409 participants of the Renal REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study. PREDICTOR: Family history of ESRD was ascertained by asking "Has anyone in your immediate family ever been told that he or she had kidney failure? This would be someone who is on or had been on dialysis or someone who had a kidney transplant." STUDY OUTCOMES: Incidence rate for ESRD. MEASUREMENTS: Morning urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Incident cases of ESRD were identified through the US Renal Data System. RESULTS: A family history of ESRD was reported by 11.1% of participants. Mean eGFRs for those with and without a family history of ESRD were 87.5 +/- 22.2 (SD) and 86.5 +/- 19.3 mL/min/1.73 m(2), respectively (P = 0.05) and the respective geometric mean ACRs were 12.2 and 9.7 mg/g (P < 0.001). ESRD incidence rates for those with and without a family history of ESRD were 244.3 and 106.1/100,000 person-years, respectively. After adjusting for age, sex, and race, the ESRD HR for those with versus those without a family history of ESRD was 2.13 (95% CI, 1.18-3.83). Adjustment for comorbid conditions and socioeconomic status attenuated this association (HR, 1.82; 95% CI, 1.00-3.28), and further adjustment for baseline eGFR and ACR completely attenuated the association between family history of ESRD and incident ESRD (HR, 1.12; 95% CI, 0.69-1.80). LIMITATIONS: The report of a family history of ESRD was not validated. CONCLUSION: Family history of ESRD is common in older Americans and the increased risk of ESRD associated with a family history reflects lower GFR, higher albuminuria, and comorbid conditions. PMID- 22078059 TI - Using experimental human influenza infections to validate a viral dynamic model and the implications for prediction. AB - The aim of this work was to use experimental infection data of human influenza to assess a simple viral dynamics model in epithelial cells and better understand the underlying complex factors governing the infection process. The developed study model expands on previous reports of a target cell-limited model with delayed virus production. Data from 10 published experimental infection studies of human influenza was used to validate the model. Our results elucidate, mechanistically, the associations between epithelial cells, human immune responses, and viral titres and were supported by the experimental infection data. We report that the maximum total number of free virions following infection is 10(3)-fold higher than the initial introduced titre. Our results indicated that the infection rates of unprotected epithelial cells probably play an important role in affecting viral dynamics. By simulating an advanced model of viral dynamics and applying it to experimental infection data of human influenza, we obtained important estimates of the infection rate. This work provides epidemiologically meaningful results, meriting further efforts to understand the causes and consequences of influenza A infection. PMID- 22078061 TI - [Prevention of drug administration errors: proposition of improved presentation using a double packing technique for high-risk drugs]. PMID- 22078060 TI - Epigenetics in breast cancer: what's new? AB - Epigenetic changes are critical for development and progression of cancers, including breast cancer. Significant progress has been made in the basic understanding of how various epigenetic changes such as DNA methylation, histone modification, miRNA expression, and higher order chromatin structure affect gene expression. The present review will focus on methylation and demethylation of histones. While the acetylation of histones has been at the forefront of well characterized post-translational modifications of histones, including the development of inhibitors targeting de-acetylating enzymes, the past few years have witnessed a dramatic increase in knowledge regarding the role of histone methylation/demethylation. This is an exciting and rapidly evolving area of research, with much promise for potential clinical intervention in several cancers including breast cancer. We also summarize efforts to identity DNA methylation signatures that could be prognostic and/or predictive markers in breast cancer, focusing on recent studies using genome-wide approaches. Finally, we briefly review the efforts made by both the National Institutes of Health Epigenome Project and The Cancer Genome Atlas, especially highlighting the study of breast cancer epigenetics, exciting technological advances, potential roadblocks, and future directions. PMID- 22078062 TI - Environmentally coordinated epigenetic silencing of FLC by protein and long noncoding RNA components. AB - In Arabidopsis, the role of the vernalization pathway is to repress expression of a potent floral repressor, FLOWERING LOCUS C (FLC), after a sufficient period of winter cold has been perceived. Following winter, the lack of FLC expression allows unimpeded operation of the photoperiod pathway and hence rapid flowering of vernalized plants in spring via the activation of floral integrator genes. Molecular studies revealed that regulation of the key floral repressor, FLC, is under the control of the interplay between Trithorax group (TrxG)-mediated activation and Polycomb group (PcG)-mediated repression. On-off switch of genes by TrxG and PcG is an evolutionarily conserved mechanism to coordinate cellular identity in eukaryotes. Regulation of FLC by external cues provides an excellent model system to study mechanisms in which cell identity is influenced by environment. In this review, we discuss coordinated contributions by protein and long noncoding RNA components to this environmentally induced epigenetic switch of a developmental program in plants. PMID- 22078063 TI - Secondary cell wall patterning during xylem differentiation. AB - Xylem cell differentiation involves temporal and spatial regulation of secondary cell wall deposition. The cortical microtubules are known to regulate the spatial pattern of the secondary cell wall by orientating cellulose deposition. However, it is largely unknown how the microtubule arrangement is regulated during secondary wall formation. Recent findings of novel plant microtubule-associated proteins in developing xylem vessels shed new light on the regulation mechanism of the microtubule arrangement leading to secondary wall patterning. In addition, in vitro culture systems allow the dynamics of microtubules and microtubule associated proteins during secondary cell wall formation to be followed. Therefore, this review focuses on novel aspects of microtubule dynamics leading to secondary cell wall patterning with a focus on microtubule-associated proteins. PMID- 22078064 TI - The epidemiology of chronic pain in children and adolescents revisited: a systematic review. AB - Chronic and recurrent pain not associated with a disease is very common in childhood and adolescence, but studies of pain prevalence have yielded inconsistent findings. This systematic review examined studies of chronic and recurrent pain prevalence to provide updated aggregated prevalence rates. The review also examined correlates of chronic and recurrent pain such as age, sex, and psychosocial functioning. Studies of pain prevalence rates in children and adolescents published in English or French between 1991 and 2009 were identified using EMBASE, Medline, CINAHL, and PsycINFO databases. Of 185 published papers yielded by the search, 58 met inclusion criteria and were reviewed, and 41 were included in the review. Two independent reviewers screened papers for inclusion, extracted data, and assessed the quality of studies. Prevalence rates ranged substantially, and were as follows: headache: 8-83%; abdominal pain: 4-53%; back pain: 14-24%; musculoskeletal pain: 4-40%; multiple pains: 4-49%; other pains: 5 88%. Pain prevalence rates were generally higher in girls and increased with age for most pain types. Lower socioeconomic status was associated with higher pain prevalence especially for headache. Most studies did not meet quality criteria. PMID- 22078065 TI - Advising people with back pain to take time off work: a survey examining the role of private musculoskeletal practitioners in the UK. AB - Research has demonstrated that health care practitioners' adherence to guidelines for managing low back pain (LBP) remain suboptimal in recommending work absence, but specific beliefs about their role in maintaining patients at work have not been adequately researched. We examined private musculoskeletal practitioners' (chiropractors, osteopaths, and physiotherapists) beliefs and reported clinical behaviours in reference to patients' work. A cross-sectional postal questionnaire of 900 musculoskeletal practitioners included the Attitudes to Back pain in musculoskeletal practitioners questionnaires, reported frequency of four work related behaviours, and a new measure of practitioners' work-related beliefs. Data from 337 respondents (37%) were analysed. Eighty percent of respondents reported recommending work absence to patients with LBP sometimes, and 14% recommended a work absence often or always. Seventy percent of practitioners never visit the patient's workplace. Most practitioners report that they prescribe exercises that can be carried out at work. Physiotherapists visited the workplace more frequently and gave less sick leave certification than either of the other groups. They also regarded work as more beneficial and less of a threat to exacerbate patients' LBP. There were small but significant correlations between work-related beliefs and reported behaviours. Our study confirms that, in contrast to current guidelines, many practitioners believe that LBP necessitates work absence. Overall, practitioners perceived their role in returning patients to work as limited, and believed that direct contact with employers was beyond their remit. In the UK, physiotherapists appear to be better placed to liaise with work in terms of both their beliefs and activities. PMID- 22078066 TI - Mobilization of lymphoblasts from bone marrow to peripheral blood in childhood acute lymphoblastic leukaemia: role of 9-O-acetylated sialoglycoproteins. AB - Childhood acute lymphoblastic leukaemia is characterized by aberrant proliferation and accumulation of malignant lymphoblasts in bone marrow (BM), followed by their migration into circulation. An enhanced cell-surface expression of ALL-associated 9-O-acetylated sialoglycoproteins (Neu5,9Ac(2)-GPs) was demonstrated. Present investigation reports a positive correlation between the increased density of Neu5,9Ac(2)-GPs on lymphoblasts and their mobilization from BM involving enhanced Neu5,9Ac(2) on CD45 demonstrating modulation of FAK and ERK molecules. In contrast, a small population of cells, identified as haematopoietic precursors, with comparatively lesser Neu5,9Ac(2)-GPs showed increased binding towards BM stroma. Thus, Neu5,9Ac(2)-GPs is a developmentally regulated oncofoetal antigen, whose up-regulation is imperative in the interaction between lymphoblasts and BM stroma, governing their mobilization into circulation. PMID- 22078067 TI - Blockade of leukocyte haptokinesis and haptotaxis by ketoprofen, diclofenac and SC-560. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) represent a one of the most widely used anti-inflammatory substances. Their anti-inflammatory effects are mainly based on inhibition of cyclooxygenase. The potential direct effect of NSAID on leukocyte migration was poorly investigated. Using time-lapse microscopy and 96-well fluorescence-based assay, we studied the effect of three different NSAID, ketoprofen, diclofenac and SC-560, on leukocyte haptokinesis and haptotaxis in vivo and in vitro. RESULTS: NSAID induced an immediate inhibiting effect on leukocyte migration both in vitro and in vivo. This effect was dose dependent and was not restricted to a specific type of leukocytes. The inhibition of leukocyte migration by NSAID was partially re-stored after removal of inhibiting agent. Only complete blockade of leukocyte migration was accompanied by a strong reduction of [Ca(2+)]i. CONCLUSIONS: NSAID strongly supress leukocyte migration. The results of the present study may have important clinical implications since blockade of leukocyte migration can be achieved after topical application of NSAID. PMID- 22078068 TI - Centromedian thalamic nuclei deep brain stimulation in refractory status epilepticus. AB - BACKGROUND: Refractory status epilepticus (RSE) is associated with high mortality. We report a potential treatment alternative. HYPOTHESIS: Deep brain stimulation (DBS) of the centromedian thalamic nuclei (CMN) can be effective in the treatment of RSE. METHODS: Report of the evolution of RSE after DBS of the CMN in a 27-year-old man. RESULTS: In the course of an encephalopathy of unknown origin, and after a cardiac arrest, the patient developed RSE with myoclonic jerks and generalized tonic-clonic seizures. The EEG showed continuous generalized periodic epileptiform discharges (GPEDS). Five weeks after RSE onset, bilateral DBS of the CMN was started. This treatment was immediately followed by disappearance of tonic-clonic seizures and GPEDS, suggesting a resolution of RSE. The patient continued having multifocal myoclonic jerks, probably subcortical in origin, which resolved after 4 weeks. The patient remained clinically stable for 2 months in a persistent vegetative state. CONCLUSIONS: The remission of RSE, the abolition of GPEDS, and the patient survival suggest that DBS of the CMN may be efficacious in the treatment of refractory, generalized status epilepticus. PMID- 22078069 TI - Atomistic aspects of ductile responses of cubic silicon carbide during nanometric cutting. AB - Cubic silicon carbide (SiC) is an extremely hard and brittle material having unique blend of material properties which makes it suitable candidate for microelectromechanical systems and nanoelectromechanical systems applications. Although, SiC can be machined in ductile regime at nanoscale through single-point diamond turning process, the root cause of the ductile response of SiC has not been understood yet which impedes significant exploitation of this ceramic material. In this paper, molecular dynamics simulation has been carried out to investigate the atomistic aspects of ductile response of SiC during nanometric cutting process. Simulation results show that cubic SiC undergoes sp3-sp2 order disorder transition resulting in the formation of SiC-graphene-like substance with a growth rate dependent on the cutting conditions. The disorder transition of SiC causes the ductile response during its nanometric cutting operations. It was further found out that the continuous abrasive action between the diamond tool and SiC causes simultaneous sp3-sp2 order-disorder transition of diamond tool which results in graphitization of diamond and consequent tool wear. PMID- 22078070 TI - Growth, seed development and genetic analysis in wild type and Def mutant of Pisum sativum L. AB - BACKGROUND: The def mutant pea (Pisum sativum L) showed non-abscission of seeds from the funicule. Here we present data on seed development and growth pattern and their relationship in predicting this particular trait in wild type and mutant lines as well as the inheritance pattern of the def allele in F2 and F3 populations. FINDINGS: Pod length and seed fresh weight increase with fruit maturity and this may affect the abscission event in pea seeds. However, the seed position in either the distal and proximal ends of the pod did not show any difference. The growth factors of seed fresh weight (FW), width of funicles (WFN), seed width (SW) and seed height (SH) were highly correlated and their relationships were determined in both wild type and def mutant peas. The coefficient of determination R2 values for the relationship between WFN and FW, SW and SH and their various interactions were higher for the def dwarf type. Stepwise multiple regression analysis showed that variation of WFN was associated with SH and SW. Pearson's chi square analysis revealed that the inheritance and segregation of the Def locus in 3:1 ratio was significant in two F2 populations. Structural analysis of the F3 population was used to confirm the inheritance status of the Def locus in F2 heterozygote plants. CONCLUSIONS: This study investigated the inheritance of the presence or absence of the Def allele, controlling the presence of an abscission zone (AZ) or an abscission-less zone (ALZ) forming in wild type and mutant lines respectively. The single major gene (Def) controlling this phenotype was monogenic and def mutants were characterized and controlled by the homozygous recessive def allele that showed no palisade layers in the hilum region of the seed coat. PMID- 22078071 TI - Quality of hospital care for sick newborns and severely malnourished children in Kenya: a two-year descriptive study in 8 hospitals. AB - BACKGROUND: Given the high mortality associated with neonatal illnesses and severe malnutrition and the development of packages of interventions that provide similar challenges for service delivery mechanisms we set out to explore how well such services are provided in Kenya. METHODS: As a sub-component of a larger study we evaluated care during surveys conducted in 8 rural district hospitals using convenience samples of case records. After baseline hospitals received either a full multifaceted intervention (intervention hospitals) or a partial intervention (control hospitals) aimed largely at improving inpatient paediatric care for malaria, pneumonia and diarrhea/dehydration. Additional data were collected to: i) examine the availability of routine information at baseline and their value for morbidity, mortality and quality of care reporting, and ii) compare the care received against national guidelines disseminated to all hospitals. RESULTS: Clinical documentation for neonatal and malnutrition admissions was often very poor at baseline with case records often entirely missing. Introducing a standard newborn admission record (NAR) form was associated with an increase in median assessment (IQR) score to 25/28 (22-27) from 2/28 (1-4) at baseline. Inadequate and incorrect prescribing of penicillin and gentamicin were common at baseline. For newborns considerable improvements in prescribing in the post baseline period were seen for penicillin but potentially serious errors persisted when prescribing gentamicin, particularly to low-birth weight newborns in the first week of life. Prescribing essential feeds appeared almost universally inadequate at baseline and showed limited improvement after guideline dissemination. CONCLUSION: Routine records are inadequate to assess newborn care and thus for monitoring newborn survival interventions. Quality of documented inpatient care for neonates and severely malnourished children is poor with limited improvement after the dissemination of clinical practice guidelines. Further research evaluating approaches to improving care for these vulnerable groups is urgently needed. We also suggest pre-service training curricula should be better aligned to help improve newborn survival particularly. PMID- 22078072 TI - Starting or switching to biphasic insulin aspart 30 (BIAsp 30) in type 2 diabetes: a multicenter, observational, primary care study conducted in Finland. AB - AIMS: Assess safety and glycaemic control in patients initiating insulin with, or switching from basal insulin to, biphasic insulin aspart 30/70 (BIAsp 30) in primary care in Finland. METHODS: A non-randomised, non-interventional, open label, 26-week study of type 2 diabetes (T2D) patients prescribed BIAsp 30 by their physician, who determined starting dose, titration and injection frequency. RESULTS: 496 patients provided safety data (insulin-naive n=197; prior insulin n=299 [84.9% received NPH insulin]). Three patients (0.6%) reported four SADRs (three hypoglycaemia, one hypoglycaemia with unconsciousness). HbA1c was significantly (p<0.0001) reduced after 26 weeks' BIAsp 30 therapy (final dose): insulin-naive -1.4% (44.4 IU); prior insulin -1.1% (77.4 IU). HbA1c<7.0% was achieved by 10% of insulin-naive patients at baseline and 51% at 26-week follow up. In the prior insulin group, 7% and 30% of patients had HbA1c<7.0% at baseline and 26 weeks, respectively. Minor hypoglycaemia increased significantly from baseline to study end: insulin-naive 0.66-6.45 events/patient/year (p<0.0001); prior insulin 5.11-8.58 events/patient/year (p<0.05). Weight increased by 1.0 kg (insulin-naive) and 1.3 kg (previous insulin). CONCLUSION: BIAsp 30, initiated and titrated in T2D patients in primary care in Finland, showed a good safety profile and significantly improved glycaemic control. PMID- 22078073 TI - Metabolic syndrome in adult cancer survivors: a meta-analysis. AB - BACKGROUND: Cross-sectional studies have reported inconsistent findings on whether the risk of metabolic syndrome is high among cancer survivors. We conducted a meta-analysis of cross-sectional studies. METHODS: We searched MEDLINE (PubMed) and EMBASE in April 2010. Two evaluators independently reviewed and selected articles, based on pre-determined selection criteria. RESULTS: Out of 257 articles meeting our initial criteria, 9 cross-sectional studies, which involved 6763 participants (1762 cases and 5001 controls) were included in the final analysis. Compared with the healthy control groups, the cancer survivors were at an increased risk of metabolic syndrome, in the random-effects meta analysis of all 9 cross-sectional studies (OR=1.84; 95% CI=1.14-2.97; I(2)=80.5). In the subgroup meta-analysis by cancer type, a significant positive association was observed for hematologic malignancies, including ALL (acute lymphoblastic leukemia), AML (acute myelogenous leukemia), NHL (non-Hodgkin's lymphoma), and CML (chronic myelogenous leukemia) (OR=1.94; 95% CI=1.06-3.55; I(2)=68.1%), whereas no significant association was found for non-hematologic malignancies, including testicular tumor, prostate cancer, sarcoma, and epithelial ovarian cancer. CONCLUSIONS: Our meta-analyses of cross-sectional studies found that adult cancer survivors with hematologic malignancies were at an increased risk of metabolic syndrome. PMID- 22078074 TI - Elevated micronuclei frequency in type 2 diabetes with high glycosylated hemoglobin. AB - AIM: The role of oxidative damage to DNA due to hyperglycemia is well known. In the current study we have evaluated the induction of micronuclei due to increased glycosylation in type 2 diabetes. METHODS: Forty-nine subjects divided into two groups of normoglycemic controls and type 2 diabetic cases were recruited in the study. Whole blood was cultured and micronuclei were scored in all the cases. This was correlated with age, sex, blood glucose levels and glycosylated hemoglobin. RESULTS: Age and sex matched diabetic patients had an increased micronuclei frequency in response to elevated glycosylation of hemoglobin (R(2)=0.229, p=0.037) compared to normoglycemic subjects. CONCLUSION: The increased glycosylation seems to induce oxidative damage in the DNA of the diabetic patients, which manifests as an increased micronuclei frequency. This has a potential to be used as a biomarker for subsequent diabetic complications. PMID- 22078075 TI - Detection of benzo(a)pyrene photodegradation products using DNA electrochemical sensors. AB - The reactivity of photodegradation products of benzo(a)pyrene vs. DNA has been assessed using both genomic and oligonucleotide based DNA electrochemical sensors. The kinetic of a photooxidation reaction of benzo(a)pyrene (BaP) carried out in controlled conditions using a 6 W UV lamp peaked at 365 nm has been studied using LC with fluorimetric detection. Degradation of benzo(a)pyrene by both UV and UV/H(2)O(2) exhibited pseudo-first-order reaction kinetics with half lives ranging from 3.0 to 9.8h depending on the pH and on the amount of H(2)O(2). The oxidation products of benzo(a)pyrene obtained in different conditions were tested on genomic ssDNA electrochemical sensors obtained via immobilisation of salmon testis ss-DNA on graphite screen-printed electrodes. Guanines oxidation signals obtained using chronopotentiometry were used to detect the interaction of the products with DNA. The dose-response curve obtained with benzo(a)pyrene incubated 24 h at pH 4.7 was different from that of the parent compound indicating a different type of interaction with DNA. A DNA hybridisation sensor was also assembled using a thiolated/biotynilated 24-mer oligonucleotide immobilised on a gold screen-printed electrode and avidin-alkaline phosphatase conjugate. A voltammetric detection of naphtol was used to detect the hybridisation reaction. A net inhibition of the hybridisation reaction was observed after incubation with benzo(a)pyrene oxidation products that was attributed to the formation of stable adducts with the guanines of the biotinylated strand. LC-MS-MS studies of the oxidation products confirmed the presence of chemical species potentially forming adducts with DNA. The data reported demonstrate that DNA electrochemical sensors have the potential to be used to monitor remediation processes and to assess the potential toxicity vs. DNA of chemicals forming stable DNA adducts. PMID- 22078076 TI - Staff outcomes from the caring for aged dementia care resident study (CADRES): a cluster randomised trial. AB - BACKGROUND: Dementia care mapping and person centred care are well-accepted as processes for improving care and well-being for persons with dementia living in the residential setting. However, the impact of dementia care mapping and person centred care on staff has not been well researched. OBJECTIVES: The impact of person centred care and dementia care mapping compared to each other and to usual dementia care on staff outcomes was examined in terms of staff burnout, general well-being, attitudes and reactions towards resident behavioural disturbances, perceived managerial support, and quality of care interactions. DESIGN: A cluster randomised, controlled trial. SETTINGS: The study was conducted between 2005 and 2007 in 15 residential aged care sites in the Sydney metropolitan area, Australia, with comparable management structures, staffing mix and ratios, and standards of care. PARTICIPANTS: 194 consenting managers, nurses, therapists and nurse assistants working in the participating sites. METHODS: Intervention care sites received training and support in either person centred care (n=5) or dementia care mapping (n=5); control sites continued with usual dementia care (n=5). Staff outcomes of those three groups were assessed before, directly after the four month intervention (post) and after a further four months (follow-up). The primary outcome measures were the Maslach Burnout Inventory-Human Services Survey and the 12-item General Health Questionnaire. Analysis involved repeated measures analyses of variance for each of the outcome measures and adjustment for potential confounders to limit bias. RESULTS: The Maslach Burnout Inventory-Human Services Survey results showed that change over time in emotional exhaustion scores differed between the three groups. Post-hoc analyses for each group separately revealed that the only significant time effect was in the dementia care mapping group (p=0.006), with emotional exhaustion scores declining over time. At baseline, more perceived support from management was associated with less emotional exhaustion (r(s)=0.26, p=0.004, n=122) and less depersonalisation (r(s)=0.21, p=0.023, n=122), but not for any of the other outcome measures. CONCLUSIONS: This study has shown that person centred approaches of care, in particular with dementia care mapping, may contribute to reducing staff job related burnout. The findings also highlight a potentially important role of managerial support and a whole of system approach. PMID- 22078077 TI - Optical properties of organic nonlinear optical crystal--a combined experimental and theoretical study. AB - The optical properties of the synthesized imidazole derivative, 1-(4 methoxyphenyl)-4,5-diphenyl-2-styryl-1H-imidazole, has been studied both experimentally and theoretically. Fluorescence enhancement have been found in the presence of transition metal ions and this may result from the suppression of radiationless transitions from the n-pi* state in the chemosensors. Quantum chemical calculations of heat of formation, optimized geometry, NLO, HOMO-LUMO, MEP and NBO analysis of 1-(4-methoxyphenyl)-4,5-diphenyl-2-styryl-1H-imidazole (mpdsi) have been carried out by using density functional theory (DFT/B3LYP) method with 6-31G(d,p) as basis set. This chromophore possess more appropriate ratio of off-diagonal versus diagonal beta tensorial component (r=beta(xyy)/beta(xxx)=-0.002) which reflects the inplane non-linearity anisotropy. Since they have largest MUbeta(0) value, the reported imidazole can be used as potential NLO material. The solvent effect on the absorption and fluorescence has been analyzed simultaneously. PMID- 22078078 TI - Reliability of dissociation constants and resolution capability of SQUAD(84) and SPECFIT/32 in the regression of multiwavelength spectrophotometric pH-titration data. AB - The resolving power of multicomponent spectral analysis and the computation reliability of the stability constants and molar absorptivities determined for five variously protonated anions of physostigmine salicylate by the SQUAD(84) and SPECFIT/32 programs has been examined with the use of simulated and experimental spectra containing overlapping spectral bands. The reliability of the dissociation constants of drug was proven with goodness-of-fit tests and by examining the influence of pre-selected noise level s(inst)(A) in synthetic spectra regarding the precision s(pK) and also accuracy of the estimated dissociation constants. Precision was examined as the linear regression model s(pK)=beta(0)+beta(1)s(inst)(A). In all cases the intercept beta(0) was statistically insignificant. When an instrumental error s(inst)(A) is small and less than 0.5 mAU, the parameters' estimates are nearly the same as the bias DeltapK=pK(a,calc)-pK(a,true) is quite negligible. In all four dissociation constants the bias seems to be quite small even though for pK(a4) it is a little bit higher, i.e., +0.05 for s(inst)(A) about 1.0 mAU. In the interval of s(inst)(A) from 0.1 to 1.0 mAU all four dissociation constants pK(i) are accurate enough. Of the various regression diagnostics considered, the goodness-of-fit is the most efficient criterion of whether the parameters found adequately represent the data. The magnitude of instrumental error s(inst)(A) only slightly affects the shape of a Cattel's scree graph s(k)(A)=f(k) to determine the true number of light-absorbing species in the equilibrium mixture. PMID- 22078079 TI - Synthesis, crystal structure, and properties of a double-helical zinc(II) coordination polymer with Ozagrel drug. AB - By the reaction of Zn(OAc)(2).2H(2)O with Ozagrel, (E)-3-(4-((1H-imidazol-1 yl)methyl)phenyl)acrylic acid (Himpaa), a novel coordination polymer [Zn(impaa)(2)](n)(1) was synthesized and was characterized by IR, elemental analysis, single-crystal X-ray diffraction analysis, photoluminescence spectroscopy, and thermogravimetric and differential thermal analysis. The four coordinate Zn(II) ions are linked into 1D double-helical chain by the deprotonated impaa(-), which is extended into a 3D supramolecular structure through intermolecular C-H...O hydrogen bonds. PMID- 22078080 TI - Vibrational spectra, structure and antioxidant activity of gossypol imine derivatives. AB - The structures and tautomeric equilibria of natural polyphenol gossypol and four its imine derivatives were studied by FT-IR-, NMR-spectroscopy and quantum chemistry methods. It was shown that gossypol Schiff bases exist in solution as enamine-enamine tautomer and hydrazones as imine-imine tautomer. Infrared absorption spectra of studied compounds were simulated using the PM3 method. The fundamental vibrational frequencies were evaluated using various scale factors which yield a good agreement between observed and calculated frequencies. Free radical scavenging activity of gossypol and its imine derivatives was evaluated using DPPH method. Antioxidant activity of studied compounds was characterized. Gossypol hydrazones were shown to be more efficient, while Schiff base to be less efficient as antioxidants in comparison with gossypol itself. PMID- 22078081 TI - Associations between child sexual abuse and negative sexual experiences and revictimization among women: does measuring severity matter? AB - Women with histories of child sexual abuse (CSA) are more likely than those without such experiences to report a variety of negative sexual outcomes. This study examines the explanatory power of a CSA summed composite versus dichotomous (presence/absence) measurement in predicting a comprehensive negative sexual behavior outcome. Study participants were obtained from a community based sample examining women's sexual decision-making. The continuous CSA measurement reflects cumulative histories of CSA through a composite score capturing abuse specific characteristics. Using a cross-validation approach, the sample (n=835) was randomly split and the explanatory power of each measure was examined through a series of multiple linear regressions comparing model fit indexes and performing a formal likelihood ratio test of one model against another. All CSA measures explained a similar percentage of variance but overall the CSA summed composite explained the data significantly better in terms predicting negative sexual experiences and revictimization than a binary measure as demonstrated with the likelihood ratio test. The results were replicated by cross-validating the predictive power of the CSA composite score between the split samples. Consistency of CSA regression estimates for the summed composite between training and validation samples were also confirmed. Given the superiority of the CSA summed composites over the binary variable, we recommend using this measure when examining associations between CSA histories and negative sexual experiences and revictimization. PMID- 22078082 TI - Mercury, chronic hepatitis and hepatoma. PMID- 22078083 TI - A comparison of the degree of retraction of full-thickness supraspinatus tears with the Goutallier grading system. AB - BACKGROUND: Tears of the supraspinatus are common and incompletely understood. The degree of fatty infiltration into the muscle is perceived to be a determining factor of successful surgical repair and postoperative function. It is the hypothesis of this study that the degree of central tendon retraction (CTR) as seen on magnetic resonance imaging corresponds to the amount of fatty infiltration classified according to the Goutallier grading system. MATERIALS AND METHODS: Magnetic resonance imaging scans of the supraspinatus were reviewed in 2 identifiable groups: 143 scans with no tear (NT) and 148 scans with a full thickness tear (FTT) and CTR. The degree of CTR and the corresponding Goutallier grade were measured. The difference in Goutallier grade between the NT and FTT groups was measured with the Mann-Whitney test. The relationship between Goutallier grade and increasing amount of CTR was described by use of Spearman rank correlation. Studying the difference between the Goutallier grades and CTR was achieved by use of Mann-Whitney tests. RESULTS: Of NT scans, 100% showed Goutallier grade 0 or 1. Among FTT scans, 2 showed grade 0, 21 showed grade 1, 35 showed grade 2, 14 showed grade 3, and 76 showed grade 4. The difference was statistically significant (P < .001) between the Goutallier grade 3 and 4 scans, and the degree of Goutallier grade increased with increasing CTR (P < .001). CONCLUSION: Fatty infiltration can be directly linked to CTR and, as such, may help to determine surgical intervention between groups. PMID- 22078084 TI - A challenging diagnosis of alpha-1-antitrypsin deficiency: identification of a patient with a novel F/Null phenotype. AB - Alpha-1-antitrypsin (A1AT) deficiency is a genetic disease characterized by low levels and/or function of A1AT protein. A1AT deficiency can result in the development of COPD, liver disease, and certain skin conditions. The disease can be diagnosed by demonstrating a low level of A1AT protein and genotype screening for S and Z mutations, which are the most common. However, there are many genetic variants in A1AT deficiency, and this screening may miss rarer cases, such as those caused by dysfunctional protein. We identified a patient with a previously unreported F/null phenotype that was missed by routine screening. This case highlights the wide variation in possible mutations, limitations in diagnostics, and the importance of combining clinical suspicion with measurement of protein levels, phenotypic analysis, and in appropriate cases expanded genetic analysis. PMID- 22078085 TI - [Refractory thyroid cancers]. AB - Refractory thyroid cancers include medullary and differentiated cancers with locally advanced disease that is not amenable to surgery or with distant metastases, differentiated thyroid carcinomas being refractory to radio-iodine treatment and all anaplastic carcinomas. These carcinomas are rare, with an estimated incidence in France of 350 new cases per year. Their management may benefit from the TUTHYREF network. Kinase inhibitors inhibit kinases of the VEGF receptors, and this inhibits angiogenesis, and some of these agents also inhibit other kinases of the MAPkinase pathway. These inhibitors are effective in differentiated and medullary thyroid cancers, and induce a partial response or a long-term stabilisation in more than half of patients. Their toxicity is significant and these treatments should be given only to selected patients with locally advanced or metastatic disease, with progression or with clinical symptoms. PMID- 22078086 TI - Lung function and quality of life in survivors of the acute respiratory distress syndrome (ARDS). AB - Recent studies have begun to describe the long-term outcomes of acute respiratory distress syndrome (ARDS) survivors. These patients experience a number of physical, mental and psychological morbidities that significantly impair their health-related quality of life (HRQL). The trajectory of pulmonary recovery in survivors of ARDS, as it relates to lung function, structure and health-related quality of life (HRQL), is predictable and often persists years after hospital discharge. True pulmonary parenchymal morbidity is uncommon and when present, persistent restrictive disease is likely related to diaphragmatic weakness with a mild reduction in diffusion capacity (DLCO). Future research should focus on identifying patients at risk for long-term functional limitations and the design of rehabilitation interventions tailored to individual patient needs. PMID- 22078087 TI - Long-term successful management of an aortoesophageal fistula secondary to the ingestion of a bone. PMID- 22078088 TI - [Thyroid dysfunctions and pregnancy]. AB - Advances in understanding the physiology of the thyroid function in normal pregnancy have highlighted the importance of the consequences of abnormal thyroid function on mother and fetal outcomes. Thyroid diseases are common in young women of childbearing age while management of thyroid diseases is relatively straightforward. For each thyroid dysfunction (hypothyroxinemia, hypothyroidism, hyperthyroidism, postpartum thyroiditis), the issues with the obstetric complications of the mother and the fetus are considered. Indeed, early recognition of thyroid diseases during pregnancy and appropriate management has the potential to improve outcome for the mother and the fetus. PMID- 22078089 TI - Prone positioning in acute respiratory distress syndrome (ARDS): when and how? AB - Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure. It remains one of the most devastating conditions in the intensive care unit. Mechanical ventilation with positive end-expiratory pressure is a cornerstone therapy for ARDS patients. One adjuvant alternative is to place the patient in a prone position. Since it was first described in 1976, prone positioning has been safely employed to improve oxygenation in many patients with ARDS. Prone positioning may also minimize secondary lung injury induced by mechanical ventilation, although this benefit has not been investigated as extensively, despite its potential. In spite of a strong physiological justification, prone positioning is still not widely accepted as an adjunct therapy in ARDS patients and it is only used regularly in only 10% of ICUs. This may be explained in part by the reluctance to change position, risks and unclear effects on relevant outcomes. In this paper, we review all aspects of prone positioning, from the pathophysiology to the clinical studies of patient outcome, and we also discuss the latest controversies surrounding this treatment. PMID- 22078090 TI - [The treatment of Graves' disease: current views and controversies]. AB - One of the more prevalent among the organ-specific autoimmune diseases, Graves' disease share their chronic evolution and lack of immunomodulatory treatment. Treatment strategy has to consider as opposite options as medical conservatory or ablative approach which requires much expertise and attention to patients' wish. Whatever treatment option, it is mandatory to prevent any risk of iatrogenic hypothyroidism, especially a rise of TSH above normal limit. The long-lasting benefit-risk ratio of treatment options is of primordial importance in this usually benign but enduring disease. Occurrence of Graves' orbitopathy, a significant complication, requires a special multidisciplinary management; the same is true in the case of a current or planned pregnancy. Overall quality-of life is often markedly affected by Graves' disease; this should not be overlooked. Smoking increases relapse risk after a course of antithyroid drug; it also increases the risk and severity of Graves' orbitopathy. Patients must be made aware of these deleterious effects and encouraged to quit smoking. PMID- 22078091 TI - Pulmonary perfusion scintigraphy: a tool to detect the presence of pulmonary artery involvement in Takayasu's arteritis. AB - OBJECTIVE: Takayasu arteritis (TA) is a large-vessel vasculitis that can also involve pulmonary arteries. The aim of this study was to evaluate the frequency of pulmonary artery involvement in TA patients using pulmonary perfusion scintigraphy (PPS) and to determine the characteristics of patients with pulmonary artery involvement. METHODS: Twenty-one patients classified as having TA underwent PPS. PPS positivity was defined as the presence of perfusion defects with normal ventilation. TA diagnosis was assessed using American College of Rheumatology (ACR) and/or Ishikawa's modified criteria. RESULTS: Twenty-one patients (median age 36 years [range; 21-78]; 18 females) were analyzed. PPS was positive in 12 (57%) patients. Pulmonary symptoms were present in 4/12 patients with positive PPS, but none in patients with negative PPS. Among the 12 patients with positive PPS, eight patients (67%) were asymptomatic with regard to pulmonary involvement. No difference was noted between patients with positive and negative PPS with respect to general characteristics, vascular involvement, biological parameters or treatment regimen. PPS sensitivity was 100%, specificity at 53% and predictive negative value at 100% in patients with TA relative to the presence of pulmonary symptoms. CONCLUSION: Although frequent, pulmonary artery involvement in TA is often asymptomatic. Its systematic detection by PPS could be valuable in the diagnosis of TA. PMID- 22078092 TI - [Thyroid: model or victim?]. PMID- 22078093 TI - Noninvasive detection of intimal xanthoma using combined ultrasound, strain rate and photoacoustic imaging. AB - BACKGROUND AND MOTIVATION: The structure, composition and mechanics of carotid artery are good indicators of early progressive atherosclerotic lesions. The combination of three imaging modalities (ultrasound, strain rate and photoacoustic imaging) which could provide corroborative information about the named arterial properties could enhance the characterization of intimal xanthoma. METHODS: The experiments were performed using a New Zealand white rabbit model of atherosclerosis. The aorta excised from an atherosclerotic rabbit was scanned ex vivo using the three imaging techniques: (1) ultrasound imaging of the longitudinal section: standard ultrasound B-mode (74Hz frame rate); (2) strain rate imaging: the artery was flushed with blood and a 1.5Hz physiologic pulsation was induced, while the ultrasound data were recorded at higher frame rate (296Hz); (3) photoacoustic imaging: the artery was irradiated with nanosecond pulsed laser light of low fluence in the 1210-1230nm wavelength range and the photoacoustic data was recorded at 10Hz frame rate. Post processing algorithms based on cross-correlation and optical absorption variation were implemented to derive strain rate and spectroscopic photoacoustic images, respectively. RESULTS: Based on the spatio-temporal variation in displacement of different regions within the arterial wall, strain rate imaging reveals differences in tissue mechanical properties. Additionally, spectroscopic photoacoustic imaging can spatially resolve the optical absorption properties of arterial tissue and identify the location of lipid pools. CONCLUSIONS: The study demonstrates that ultrasound, strain rate and photoacoustic imaging can be used to simultaneously evaluate the structure, the mechanics and the composition of atherosclerotic lesions to improve the assessment of plaque vulnerability. PMID- 22078094 TI - Anisotropy of Lamb and SH waves propagation in langasite single crystal plates under the influence of dc electric field. AB - Paper is presented the results of computer simulation. Effect of the homogeneous dc electric field influence on the propagation of zero and first order Lamb and SH waves in piezoelectric langasite single crystal plates for a lot of cuts and directions have been calculated. Crystalline directions and cuts with maximal and minimal influence of dc electric field have indicated. Effect of hybridization of plate modes has been discussed. PMID- 22078095 TI - Prevalence of hepatitis B virus infection in The Netherlands in 1996 and 2007. AB - We aimed to assess differences in the prevalence of hepatitis B virus (HBV) infection in The Netherlands between 1996 and 2007, and to identify risk factors for HBV infection in 2007. Representative samples of the Dutch population in 1996 and 2007 were tested for antibodies to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg) and HBV-DNA. In 2007, the weighted anti-HBc prevalence was 3.5% (95% CI 2.2-5.5) and the HBsAg prevalence was 0.2% (95% CI 0.1-0.4). In indigenous Dutch participants, the anti-HBc prevalence was lower in 2007 than in 1996 (P=0.06). First-generation migrants (FGMs) had a 13-fold greater risk of being HBsAg- and/or HBV-DNA-positive than indigenous Dutch participants. In indigenous Dutch participants, risk factors for anti-HBc positivity were older age and having received a blood product before 1990. In FGMs, being of Asian origin was a risk factor. In second-generation migrants, having a foreign-born partner and injecting drug use were risk factors. FGMs are the main target group for secondary HBV prevention in The Netherlands. PMID- 22078096 TI - A new simple approach for the determination of pyrimidine 5'-nucleotidase activity in human erythrocytes using an ELISA reader. AB - INTRODUCTION: Pyrimidine 5' nucleotidase type I (P5'N-1) deficiency is the most frequent abnormality of cell nucleotide metabolism causing hereditary non spherocytic hemolytic anemia (HNSHA). The aim of this study was to develop a simple method of determination of P5'N-1 activity in human erythrocytes using an ELISA reader METHODS: Determination of P5'N-1 activity is based on the liberation of inorganic phosphorus (Pi) after incubation with uridine monophosphate/cytidine monophosphate. Inorganic phosphorus (Pi), a product of the enzymatic reaction is directly quantitated from its ultraviolet absorbance. Purine/Pyrimidine nucleotides ratio (OD 260: OD 280) was also measured RESULTS: P5'N-1 deficient patients showed reduction in P5'N-1 activity (Mean +/- SD; 4.06 +/- 0.66 using an ELISA reader & 6.25 +/- 1.37 using a spectrophotometer) as compared to the normal control group (ELISA reader: 13.24 +/- 3.42 & Spectrophotometer: 18.25 +/- 3.20). Heterozygotes showed intermediate activity (ELISA reader: 6.06 +/- 0.48 & Spectrophotometer: 8.06 +/- 1.28), however they would have been missed on screening using the Purine/Pyrimidine nucleotides ratio CONCLUSION: Determination of P5'N-1 activity by using an ELISA reader is a new, simple, less time consuming and reliable method. It also avoids the use of radioactive material or HPLC which is a significant advantage. PMID- 22078098 TI - Myoblasts generated by lentiviral mediated MyoD transduction of myotonic dystrophy type 1 (DM1) fibroblasts can be used for assays of therapeutic molecules. AB - BACKGROUND: Myotonic dystrophy type 1 (DM1) is the most common muscle dystrophy in adults. The disease is caused by a triplet expansion in the 3'end of the myotonic dystrophy protein kinase (DMPK) gene. In order to develop a human cell model for investigation of possible effects of antisense and RNAi effector molecules we have used lentiviral mediated myoD-forced myogenesis of DM1 patient fibroblasts. FINDINGS: Transduced fibroblasts show a multinuclear phenotype and express the differentiation marker myogenin. Furthermore, fluorescence in situ hybridization (FISH) analysis revealed a statistical significant increase in the amount of nuclear foci in DM1 patient fibroblasts after myogenesis. Finally, no nuclear foci were found after treatment with oligonucleotides targeting the repeat expansions. CONCLUSIONS: The abundance of nuclear foci in DM1 patient fibroblasts increase following myogenesis, as visualized by FISH analysis. Foci were eradicated after treatment with antisense oligonucleotides. Thus, we propose that the current cell model is suitable for testing of novel treatment modalities. PMID- 22078097 TI - Breast cancer epithelial-to-mesenchymal transition: examining the functional consequences of plasticity. AB - The epithelial-to-mesenchymal transition (EMT) is a critical developmental process that has recently come to the forefront of cancer biology. In breast carcinomas, acquisition of a mesenchymal-like phenotype that is reminiscent of an EMT, termed oncogenic EMT, is associated with pro-metastatic properties, including increased motility, invasion, anoikis resistance, immunosuppression and cancer stem cell characteristics. This oncogenic EMT is a consequence of cellular plasticity, which allows for interconversion between epithelial and mesenchymal like states, and is thought to enable tumor cells not only to escape from the primary tumor, but also to colonize a secondary site. Indeed, the plasticity of cancer cells may explain the range of pro-metastatic traits conferred by oncogenic EMT, such as the recently described link between EMT and cancer stem cells and/or therapeutic resistance. Continued research into this relationship will be critical in developing drugs that block mechanisms of breast cancer progression, ultimately improving patient outcomes. PMID- 22078100 TI - Dr. Vince Hetherington and the Federation Internacionale des Podologues. PMID- 22078099 TI - Fortunella margarita transcriptional reprogramming triggered by Xanthomonas citri subsp. citri. AB - BACKGROUND: Citrus canker disease caused by the bacterial pathogen Xanthomonas citri subsp. citri (Xcc) has become endemic in areas where high temperature, rain, humidity, and windy conditions provide a favourable environment for the dissemination of the bacterium. Xcc is pathogenic on many commercial citrus varieties but appears to elicit an incompatible reaction on the citrus relative Fortunella margarita Swing (kumquat), in the form of a very distinct delayed necrotic response. We have developed subtractive libraries enriched in sequences expressed in kumquat leaves during both early and late stages of the disease. The isolated differentially expressed transcripts were subsequently sequenced. Our results demonstrate how the use of microarray expression profiling can help assign roles to previously uncharacterized genes and elucidate plant pathogenesis response related mechanisms. This can be considered to be a case study in a citrus relative where high throughput technologies were utilized to understand defence mechanisms in Fortunella and citrus at the molecular level. RESULTS: cDNAs from sequenced kumquat libraries (ESTs) made from subtracted RNA populations, healthy vs. infected, were used to make this microarray. Of 2054 selected genes on a customized array, 317 were differentially expressed (P < 0.05) in Xcc challenged kumquat plants compared to mock-inoculated ones. This study identified components of the incompatible interaction such as reactive oxygen species (ROS) and programmed cell death (PCD). Common defence mechanisms and a number of resistance genes were also identified. In addition, there were a considerable number of differentially regulated genes that had no homologues in the databases. This could be an indication of either a specialized set of genes employed by kumquat in response to canker disease or new defence mechanisms in citrus. CONCLUSION: Functional categorization of kumquat Xcc-responsive genes revealed an enhanced defence-related metabolism as well as a number of resistant response-specific genes in the kumquat transcriptome in response to Xcc inoculation. Gene expression profile(s) were analyzed to assemble a comprehensive and inclusive image of the molecular interaction in the kumquat/Xcc system. This was done in order to elucidate molecular mechanisms associated with the development of the hypersensitive response phenotype in kumquat leaves. These data will be used to perform comparisons among citrus species to evaluate means to enhance the host immune responses against bacterial diseases. PMID- 22078101 TI - What stops children with a chronic illness accessing health care: a mixed methods study in children with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). AB - BACKGROUND: Paediatric Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is relatively common and disabling with a mean time out of school of more than one academic year. NICE guidelines recommend referral to specialist services immediately if severely affected, within 3 months if moderately affected and within 6 months if mildly affected. However, the median time-to-assessment by a specialist service in the UK is 18 months. This study used a mixed-methods approach to examine factors associated with time taken to access specialist services. METHODS: Time-to-assessment was analysed as a continuous "survival time" variable in Cox regression models using data from self-completed assessment forms for children attending a regional specialist CFS/ME service between January 2006 and December 2009. Semi-structured interviews about barriers experienced in accessing healthcare for their child were conducted with nine parents of children aged < 17 years (8 individual and one parent couple). Interviews were digitally recorded and analysed using "thematic analysis". RESULTS: 405 children were assessed between 2006 and 2009 and information on school attendance was available on 388. Only 1/125 with severe CFS/ME and 49/263 (19%) with mild to moderate CFS/ME were seen within NICE recommended timeframe. Increased fatigue was associated with shorter time to assessment (HR = 1.15; 95% CI 1.03, 1.29 per unit increase in Chalder fatigue score; P = 0.01). Time-to-assessment was not associated with disability, mood, age or gender. Parents described difficulties accessing specialist services because of their own as well as their GP's and Paediatrician's lack of knowledge. They experienced negative attitudes and beliefs towards the child's condition when they consulted GPs, Paediatricians and Child Psychiatrists. Parents struggled to communicate an invisible illness that their child and not themselves were experiencing. CONCLUSIONS: GPs, Child Psychiatrists and Paediatricians need more knowledge about CFS/ME and the appropriate referral pathways to ensure timeliness in referral to specialist services. PMID- 22078102 TI - Long-term outcome of cap polyposis, with special reference to the effects of steroid therapy. PMID- 22078103 TI - Routine brush cytology and fluorescence in situ hybridization for assessment of pancreatobiliary strictures. AB - BACKGROUND: The specificity of brush cytology for detection of malignant pancreatobiliary strictures is high, but its sensitivity is moderate. Fluorescence in situ hybridization (FISH) can be used to detect chromosomal aneuploidy in biliary brushing specimens, and, according to some reports, it may improve the sensitivity of routine cytology. OBJECTIVE: To assess the role of routine cytology and FISH in detection of malignant pancreatobiliary strictures. DESIGN: Prospective study performed between September 2008 and August 2010. SETTING: University hospital. PATIENTS: This study involved 81 patients with bile duct or pancreatic duct strictures. INTERVENTION: Brush cytology obtained during ERCP from pancreatic duct or bile duct strictures and analysis of smears by routine cytology and FISH. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, and positive and negative predictive values of routine cytology and FISH calculated with a 95% confidence interval. RESULTS: The sensitivity of routine cytology was 35.19%, and specificity was 100%. When atypia was identified as positive, the resultant sensitivity was 53.7%, and specificity was 100%. Sensitivity of FISH was 51.85%, and specificity was 88.89%. When either routine cytology was positive or atypia was observed or when the FISH result was positive, sensitivity was the highest (72.22%), and it was statistically significant in comparison with both routine cytology with atypia (P < .036) and FISH (P < .023), but specificity was lower than that of routine cytology (88.89% vs 100%). LIMITATIONS: Use of a DNA probe set that was designed for detection of urothelial carcinoma. Limited number of patients. CONCLUSION: FISH improved the sensitivity of routine cytology. Pancreatic duct brushings were a reliable material for detection of chromosomal abnormalities by FISH. The best diagnostic result was achieved by combining routine cytology with FISH. PMID- 22078104 TI - US-guided ethanol ablation of insulinomas: a new treatment option. PMID- 22078105 TI - Free-hand direct insertion ability into a simulated ex vivo model using a prototype multibending peroral direct cholangioscope (with videos). PMID- 22078106 TI - The contextual effects of social capital on health: a cross-national instrumental variable analysis. AB - Past research on the associations between area-level/contextual social capital and health has produced conflicting evidence. However, interpreting this rapidly growing literature is difficult because estimates using conventional regression are prone to major sources of bias including residual confounding and reverse causation. Instrumental variable (IV) analysis can reduce such bias. Using data on up to 167,344 adults in 64 nations in the European and World Values Surveys and applying IV and ordinary least squares (OLS) regression, we estimated the contextual effects of country-level social trust on individual self-rated health. We further explored whether these associations varied by gender and individual levels of trust. Using OLS regression, we found higher average country-level trust to be associated with better self-rated health in both women and men. Instrumental variable analysis yielded qualitatively similar results, although the estimates were more than double in size in both sexes when country population density and corruption were used as instruments. The estimated health effects of raising the percentage of a country's population that trusts others by 10 percentage points were at least as large as the estimated health effects of an individual developing trust in others. These findings were robust to alternative model specifications and instruments. Conventional regression and to a lesser extent IV analysis suggested that these associations are more salient in women and in women reporting social trust. In a large cross-national study, our findings, including those using instrumental variables, support the presence of beneficial effects of higher country-level trust on self-rated health. Previous findings for contextual social capital using traditional regression may have underestimated the true associations. Given the close linkages between self-rated health and all-cause mortality, the public health gains from raising social capital within and across countries may be large. PMID- 22078107 TI - Smart pump alerts: all that glitters is not gold. AB - INTRODUCTION: The implementation of smart pump technology can reduce the incidence of errors in the administration of intravenous drugs. This approach involves developing drug libraries for specific units and setting hard and soft limits for each drug. If a programming error occurs and these limits are exceeded, an alarm sounds and the infusion can be blocked. A detailed analysis of these alarms is essential in order not to bias the results in favor of a positive impact of this technology. PURPOSE: To evaluate the results of the first analysis of the use of smart infusion pumps and to assess the significance and practical implications of the alarms sounded. METHODS: The study was performed by a multidisciplinary team that consisted of a clinical pharmacist, a pediatrician from the pediatric intensive care unit (PICU), and the chief nurse of the unit. A library of 108 drugs was developed over a 7-month period and introduced into 40 syringe pumps and 12 volumetric pumps (Alaris((r)) with Plus software) before being applied in 6 of the 11 beds in the PICU. After four month's use, data were analyzed using the Guardrails((r)) CQI v4.1 Event Reporter program. RESULTS: Following the first four months of implementation, compliance with the drug library was 87%. By analyzing the alerts triggered, we were able to detect problems such as the need to increase user training, readjust limits that did not correspond to clinical practice, correct errors in the editing of the drug library and including a training profile. CONCLUSION: It is difficult to obtain accurate data on the true impact of this technology in the early stages of its implementation. This preliminary analysis allowed us to identify improvement measures to distinguish, in future evaluations, the alarms triggered by a real programming error from those caused by incorrect use. PMID- 22078108 TI - The role of novelty detection in food memory. AB - Memory plays a central role in food choice. Recent studies focusing on food memory in everyday eating and drinking behaviour used a paradigm based on incidental learning of target foods and unexpected memory testing, demanding recognition of the target among distractors, which deviate slightly from the target. Results question the traditional view of memory as reactivation of previous experiences. Comparison of data from several experiments shows that in incidentally learned memory, distractors are rejected, while original targets are not recognised better than by chance guessing. Food memory is tuned at detecting novelty and change, rather than at recognising a previously encountered food. PMID- 22078109 TI - Prevalence of and risk factors for abnormal ankle-brachial index in patients with type 2 diabetes. AB - BACKGROUND: The aim of the present study was to examine abnormalities in the ankle-brachial index (ABI) and related risk factors in patients with type 2 diabetes. METHODS: Between September 2003 and June 2010, the ABI was determined in 3924 outpatients attending the Diabetes Center of the People's Liberation Army 306th Hospital. In addition, demographic and laboratory data were collected. The risk factors for an abnormal ABI were determined using univariate and stepwise logistic regression analysis. RESULTS: The ABI was normal (0.91-1.3) in 93.1% of patients, low (<0.9) in 5.2%, and high (>1.3) in 1.7%. The prevalence of abnormal lower ABI was greater in elderly (>= 65 years) patients (12.2%) than in younger (< 65 years) patients (3.6%). Using normal ABI as the reference, low ABI in younger patients was found to be independently associated with HbA1c, the urinary albumin:creatinine ratio, diabetic peripheral neuropathy, diabetic retinopathy, and cerebrovascular disease. A low ABI in elderly patients was found to be independently associated with age, smoking, HbA1c, uric acid, total cholesterol, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy and cerebrovascular disease. A high ABI in younger patients was associated with being male. CONCLUSIONS: The prevalence of an abnormal ABI was high in patients with type 2 diabetes, especially elderly patients. Early identification and intensive treatment are needed to improve the quality of life and overall prognosis of patients with type 2 diabetes. PMID- 22078110 TI - Mutations in VP2 and VP1 capsid proteins increase infectivity and mouse lethality of enterovirus 71 by virus binding and RNA accumulation enhancement. AB - Enterovirus 71 (EV71) is a major cause of hand-foot-and-mouth disease. EV71 infection occasionally associates with severe neurological sequelae such as brainstem encephalitis or poliovirus-like paralysis. We demonstrated that mouse adapted strain increases infectivity, resulting in higher cytotoxicity of neuron cells and mortality to neonatal mice than a non-adapted strain. Results pointed to EV71 capsid region determining viral infectivity and mouse lethality. Mutant virus with lysine to methionine substitution at VP2(149) (VP2(149M)) or glutamine to glutamic acid substitution at VP1(145) (VP1(145E)) showed greater viral titers and apoptosis. Synergistic effect of VP2(149M) and VP1(145E) double mutations enhanced viral binding and RNA accumulation in infected Neuro-2a cells. The dual substitution mutants markedly reduced value of 50% lethal dose in neonatal mice infection, indicating they raised mouse lethality in vivo. In sum, VP2(149M) and VP1(145E) mutations cooperatively promote viral binding and RNA accumulation of EV71, contributing to viral infectivity in vitro and mouse lethality in vivo. PMID- 22078111 TI - Human adenovirus species C (HAdV-C) fiber protein. PMID- 22078112 TI - Dissipation and residue of fenpropidin in wheat and soil under field conditions. AB - The residue levels and dissipation rate of fenpropidin in wheat and soil were investigated by LC-MS/MS and GC-MS, respectively. The dissipation rates of fenpropidin were described using first-order kinetics and its half-life ranged from 3.1 to 3.3 days in wheat plants and 13.4-16.5 days in soils. During harvest time, the terminal residues of fenpropidin in wheat were below the EUs maximum residue limit (MRL, 0.5 mg kg(-1)) when collected 20 days after the final application, which suggested that the use of this fungicide was safe for humans. The residues persistence varied between two geographically separated experimental sites, indicating that it might be influenced by climate, soil properties and growth dilution factor. These results would be helpful in setting MRL guidance of fenpropidin in wheat in China. PMID- 22078113 TI - Interaction of silver nanoparticles with biological surfaces of Caenorhabditis elegans. AB - Silver nanoparticles (AgNPs) are being used in an increasing number of industrial and commercial applications; this has resulted in an increased release of AgNPs into the environment. Understanding the interaction of AgNPs with biological surfaces is important, as such understanding will facilitate predictions of the further effects of nanoparticles on biological systems. This study highlights the interaction of citrate-coated silver nanoparticles (cAgNPs) with the biological surfaces of the nematode C. elegans. General toxicity, as proxied by factors such as mortality and reproduction, was evaluated in nematode growth medium (NGM), which provides a more homogeneous distribution of cAgNPs than in K-medium. The survival and reproduction of C. elegans evidenced a clear reduction in up to 100 mg/L and 10 mg/L of cAgNPs, respectively. We also noted significant interactions of cAgNPs with the biological surfaces of C. elegans. Severe epidemic edema and burst were detected in the exposure group, which may be associated with secondary infections in soil ecosystems. We observed no evidence of cAgNPs intake by C. elegans. This is, to the best of our knowledge, the first report to investigate the nanotoxicity of cAgNPs as related to biological surfaces of C. elegans; further research is needed to study the fate of cAgNPs inside of C. elegans. PMID- 22078114 TI - Effects of the commercial formulation containing fipronil on the non-target organism Cyprinus carpio: implications for rice-fish cultivation. AB - The aim of this research was to evaluate possible toxic effects of commercial formulation containing fipronil on Cyprinus carpio tissues under rice field conditions. Antioxidant profile (SOD, catalase, glutathione S-transferase), oxidative stress parameters (thiobarbituric acid-reactive substances, protein carbonyl), and growth were investigated in carp exposed to fipronil under rice field conditions for 7, 30, and 90 days. Waterborne insecticide concentrations were measured and the detectable concentration of fipronil was observed up to 45 day after application. Common carp survival and growth was not affected by fipronil. Liver superoxide dismutase activity was enhanced while liver catalase activity was inhibited at 7, 30, and 90 days. Alterations were not observed in the glutathione S-transferase activity in any experimental periods. Protein carbonyl increased only after 30 and 90 days of exposure. The thiobarbituric acid reactive substances levels were enhanced in all analyzed tissues (liver, muscle, and brain) and periods of exposure. This study demonstrates that fipronil insecticides cause alterations in the biochemical parameters in different tissues of carp without affecting the growth or the survival of the fish. PMID- 22078116 TI - Microbial contamination of ultrasound biomicroscopy probes: evaluation of cross infection risk. PMID- 22078117 TI - Comparison of a new-generation sectorial addition multifocal intraocular lens and a diffractive apodized multifocal intraocular lens. AB - PURPOSE: To compare visual, refractive, and satisfactory outcomes between a new generation sectorial addition multifocal intraocular lens (IOL) (Lentis Mplus LS 312; study group) and a diffractive apodized multifocal IOL (Restor SN6AD1; control group). SETTING: Private practice, Driebergen, and Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands. DESIGN: Comparative case series. METHODS: Refractive and visual outcomes at near and distance, patient satisfaction, and dysphotopsia scores were recorded 3, 6, and 12 months postoperatively. RESULTS: The study group comprised 90 eyes and the control group, 143 eyes. Three months postoperatively, the mean uncorrected distance visual acuity (UDVA) was not statistically significantly different between the study group and the control group (0.04 +/- 0.15 logMAR [SD] versus 0.06 +/- 0.25 logMAR). The control group had significantly better uncorrected near visual acuity than the study group at 30 cm (0.05 +/- 0.14 logMAR versus 0.15 +/- 0.08 logMAR) and 40 cm (0.05 +/- 0.14 versus 0.16 +/- 0.21) (P<.01 and P<.03, respectively). Patients in the control group were more satisfied with their vision (P<.001). Dissatisfaction was related to younger age at surgery and male sex (P<.0001 and P<.033 respectively). Dysphotopsia occurred in approximately 18% of cases in both groups. CONCLUSIONS: The new sectorial addition multifocal IOL performed comparably to the diffractive apodized multifocal IOL in terms of UDVA and the presence of dysphotopsia. The diffractive apodized multifocal IOL performed better at 30 cm and 40 cm reading distances and had higher patient satisfaction. PMID- 22078115 TI - Following the genes: a framework for animal modeling of psychiatric disorders. AB - The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans. PMID- 22078118 TI - Recurrent iris cyst discharge. AB - A 23-year-old woman with the diagnosis of anterior uveitis in the left eye was referred to our clinic. Circumferential midzonal iris epithelial cysts were observed in the right eye and corneal endothelial pigment precipitates and diffuse pigment discharge in the anterior chamber of the left eye. Topical prednisolone acetate was prescribed. After 2 days, hyperemia and pain decreased in the left eye and started in the right eye. During the following 3 months, the patient experienced 3 similar episodes, which resulted in diffuse pigment deposition in the anterior chamber angles. Intraocular pressure (IOP) elevation was observed after 1 week and 3 weeks in the left eye and right eye, respectively. Topical antiglaucomatous medication was prescribed. Nine months after the last episode, the uncorrected distance visual acuity was 20/20 and the IOP was 15 mm Hg bilaterally. The iris showed diffuse transillumination, and the pupils were unresponsive to light. PMID- 22078119 TI - Desktop auxiliary apparatus for A-scan ultrasound: repeatability and validity. AB - PURPOSE: To evaluate the intraobserver repeatability and validity of biometric measurements with a newly developed auxiliary A-scan ultrasound apparatus at a rural clinic. SETTING: Rural county hospital in China. DESIGN: Evaluation of diagnostic technology. METHODS: Patients awaiting surgery for age-related cataract were consecutively enrolled for preoperative A-scan biometric measurements. The applanation A-scan was performed by 2 experienced nurses, with 1 using the conventional handheld method and the other using the new method with the auxiliary desktop apparatus. Two consecutive measurements were performed with each method. The 95% limits of agreement (LoA) and Bland-Altman plot were used to assess and compare the intersession measurement repeatability between the 2 methods. RESULTS: Data for 75 eyes of 75 consecutive patients were available for analysis. The mean age of the patients was 74.3 years +/- 7.4 (SD); 40.0% were men. The desktop method had a smaller standard deviation and coefficient of variance than the conventional handheld method for both measurement sessions. For intersession repeatability, the desktop method had a narrower 95% LoA range than the handheld method for all the biometry parameters. The axial length (AL) obtained with the desktop method was significantly longer than that with the handheld method (23.32 mm versus 23.14 mm; P<.01). CONCLUSION: The newly developed auxiliary device had better intraobserver repeatability and more accurate AL measurements than the conventional handheld method, making it a better option for preoperative biometric measurement of cataract patients. PMID- 22078120 TI - Toxicity comparison of intraocular azithromycin with and without a bioadhesive delivery system in rabbit eyes. AB - PURPOSE: To determine whether the addition of a bioadhesive drug-delivery system to topical azithromycin induces intraocular inflammation and damage when introduced intraocularly by different approaches and in varying doses. SETTING: John A. Moran Eye Center, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Commercial topical azithromycin 1.0% was duplicated, including the benzalkonium chloride, but without inclusion of the Durasite bioadhesive drug delivery system. Injections of 50 MUL, 25 MUL, and 10 MUL of the antibiotic solutions were administered in a masked fashion to 2 rabbits; 1 eye (study eye) in each rabbit was randomized to receive azithromycin with the delivery system and the fellow eye (control eye) to receive azithromycin without the delivery system. Two rabbits had topical drops of each solution placed after a 2.8 mm incision was created. Masked slitlamp examinations, pachymetry, and intraocular pressure (IOP) were determined 1 day and 2 days postoperatively. The animals were humanely killed, and the endothelial density and histopathology were examined. RESULTS: The IOP (P<.001), pachymetry (P<.001), and signs of inflammation (P=.38 to .003) were consistently higher in the study eye, especially at the 50 MUL dose, than in the control eye. This was confirmed by histopathology. CONCLUSION: If the drug-delivery system gains access to the anterior chamber, it may cause substantial corneal edema and inflammation, even at low doses and after topical administration. PMID- 22078121 TI - Development of a questionnaire to assess the relative subjective benefits of presbyopia correction. AB - PURPOSE: To develop a standardized questionnaire of near visual function and satisfaction to complement visual function evaluations of presbyopic corrections. SETTING: Eye Clinic, School of Life and Health Sciences, Aston University, Midland Eye Institute and Solihull Hospital, Birmingham, United Kingdom. DESIGN: Questionnaire development. METHODS: A preliminary 26-item questionnaire of previously used near visual function items was completed by patients with monofocal intraocular lenses (IOLs), multifocal IOLs, accommodating IOLs, multifocal contact lenses, or varifocal spectacles. Rasch analysis was used for item reduction, after which internal and test-retest reliabilities were determined. Construct validity was determined by correlating the resulting Near Activity Visual Questionnaire (NAVQ) scores with near visual acuity and critical print size (CPS), which was measured using the Minnesota Low Vision Reading Test chart. Discrimination ability was assessed through receiver-operating characteristic (ROC) curve analysis. RESULTS: One hundred fifty patients completed the questionnaire. Item reduction resulted in a 10-item NAVQ with excellent separation (2.92), internal consistency (Cronbach alpha = 0.95), and test-retest reliability (intraclass correlation coefficient = 0.72). Correlations of questionnaire scores with near visual acuity (r = 0.32) and CPS (r = 0.27) provided evidence of validity, and discrimination ability was excellent (area under ROC curve = 0.91). CONCLUSION: Results show the NAVQ is a reliable, valid instrument that can be incorporated into the evaluation of presbyopic corrections. PMID- 22078122 TI - Self medication with antibiotics in Yogyakarta City Indonesia: a cross sectional population-based survey. AB - BACKGROUND: Self medication with antibiotics has become an important factor driving antibiotic resistance. This study investigated the period prevalence, patterns of use, and socio-demographic factors associated with self medication with antibiotics in Yogyakarta City Indonesia. This cross-sectional population based survey used a pre-tested questionnaire which was self-administered to randomly selected respondents (over 18 years old) in Yogyakarta City Indonesia in 2010 (N = 625). Descriptive statistics, chi-square and logistic regression were applied. RESULTS: A total of 559 questionnaires were analyzed (response rate = 90%). The period prevalence of self medication with antibiotics during the month prior to the study was 7.3%. Amoxicillin was the most popular (77%) antibiotic for self medication besides ampicilline, fradiomisin-gramisidin, tetracycline, and ciprofloxacin to treat the following symptoms: the common-cold including cough and sore throat, headache, and other minor symptoms; with the length of use was mostly less than five days. Doctors or pharmacists were the most common source of information about antibiotics for self medication (52%). Antibiotics were usually purchased without prescription in pharmacies (64%) and the cost of the purchases was commonly less than US $1 (30%). Previous experience was reported to be the main reason for using non-prescribed antibiotics (54%). There were no socio-demographic variables significantly associated with the actual practice of using non-prescribed antibiotics. However, gender, health insurance, and marital status were significantly associated with the intent to self medicate with antibiotics (P < 0.05). Being male (Odds Ratio = 1.7 (1.2 - 2.6)) and having no health insurance (Odds Ratio = 1.5 (1.0 -2.3)) is associated with the intent to self medicate with antibiotics. CONCLUSIONS: This study is the first population-based study of self-medication with antibiotics among the Indonesian population. Usage of non-prescribed antibiotics as well as intent of doing so is common across socio-demographic categories. Given the findings, factors influencing people's intentions to self medicate with antibiotics are required to be investigated to better understand such behavior. Impact of health insurance coverage on self medication with antibiotics should also be further investigated. PMID- 22078123 TI - Lactase non-persistent genotype influences milk consumption and gastrointestinal symptoms in Northern Russians. AB - BACKGROUND: Milk is an important source of nutrients. The consumption of milk, however, may cause abdominal complaints in lactose intolerant individuals. The frequency of -13910C/C genotype is known to be high among Northern Russians, exceeding the prevalence in northern Europe. In our study we tested two hypotheses: 1) subjects with lactase non-persistent genotype (-13910C/C) have more gastrointestinal (GI) symptoms associated with milk 2) subjects with lactase non-persistence avoid using milk. METHODS: In total, 518 students aged 17 to 26 years were randomly selected from different departments in the Northern State Medical University (NSMU) for genotyping the lactase activity-defining -13910C/T variant. All subjects filled in a questionnaire covering their personal data, self-reported GI symptoms and milk consumption habits. RESULTS: Northern Russians consume very small amounts of milk daily. Among carriers of the lactase non persistent (LNP) genotype there were 10 percentage units of milk-consumers fewer than among lactase-persistent (LP) subjects (p = 0.03). Complaints of GI disorders caused by milk were different between the genotypes (p = 0.02). Among all types of food analyzed only milk was associated with increased GI symptoms among subjects with the LNP genotype (OR = 1.95, CI 1.03-3.69) CONCLUSIONS: Subjects with -13910C/C have more GI symptoms from milk. Subjects with lactase non-persistent genotype avoid using milk. In the case of increasing milk consumption symptoms may increase the need for medical consultation. It is thus important either for people themselves or for health care staff to be aware of lactase persistence/non-persistence. PMID- 22078124 TI - Cell-based detection of electrochemical oxidative stress by a fluorescent tryptophan intermediate. AB - The present study suggests a sensitive and rapid cell analysis method to evaluate the oxidative stress produced in a physiological culture medium, by anodic electrochemical products. The detection of these oxidizing agents, probably involving hypochlorite, is carried out by measuring the presence of an oxidized tryptophan intermediate, entrapped and stabilized in the cell cytoplasm. The formation of this tryptophan intermediate depends solely on the presence of a free tryptophan in the extracellular medium near the anode. This intermediate possesses a characteristic emission maximum at lambda~560 nm, which can be abolished by the presence of anti-oxidants in the media during the cells' exposure to electric current. However, this intermediate's emission is unaffected by increased concentrations of intracellular anti-oxidants. This suggests that the anodic produced unstable tryptophan intermediate permeates the cell plasma membrane and becomes stabilized by cytoplasmic proteins. Tryptophan oxidative intermediates with similar spectra could also be formed by the chemical reaction of hypochlorite with tryptophan in solution. The analysis of the intracellularly stabilized tryptophan intermediate by flow cytometry can be used for measuring external oxidation stress without the disturbance of intracellular anti-oxidative capacity. PMID- 22078125 TI - Hybrid biobattery based on arylated carbon nanotubes and laccase. AB - Single-walled carbon nanotubes (SWCNT) were covalently modified with anthracene and anthraquinone and used for the construction of cathodes for biocatalytic reduction of dioxygen. The nanotubes with aromatic groups casted onto the electrode increased the working surface of the electrode and enabled efficient direct electron transfer (DET) between the enzyme and the electrode. The aryl groups enter the hydrophobic pocket of the T1 center of laccase responsible for exchanging electrons with the substrate. Glassy carbon electrode covered with arylated SWCNT and coated with a layer of neutralized Nafion containing laccase was found to be a very efficient cathode in the hybrid battery. Zn wire covered with a Nafion film served as the anode. The cell parameters were determined: power density was 2 mW/cm(2) and the open circuit potential was 1.5 V. PMID- 22078126 TI - The end of gonad-centric sex determination in mammals. AB - The 20th-century theory of mammalian sex determination states that the embryo is sexually indifferent until the differentiation of gonads, after which sex differences in phenotype are caused by the differential effects of gonadal hormones. However, this theory is inadequate because some sex differences precede differentiation of the gonads and/or are determined by non-gonadal effects of the sexual inequality in the number and type of sex chromosomes. In this article, I propose a general theory of sex determination, which recognizes multiple parallel primary sex-determining pathways initiated by genes or factors encoded by the sex chromosomes. The separate sex-specific pathways interact to synergize with or antagonize each other, enhancing or reducing sex differences in phenotype. PMID- 22078127 TI - A single nucleotide polymorphism assay for the identification of unisexual Ambystoma salamanders. AB - Unisexual (all female) salamanders in the genus Ambystoma are animals of variable ploidy (2N-5N) that reproduce via a unique system of 'leaky' gynogenesis. As a result, these salamanders have a diverse array of nuclear genome combinations from up to five sexual species: the blue-spotted (A. laterale), Jefferson (A. jeffersonianum), smallmouth (A. texanum), tiger (A. tigrinum) and streamside (A. barbouri) salamanders. Identifying the genome complement, or biotype, is a critical first step in addressing a broad range of ecological and evolutionary questions about these salamanders. Previous work relied upon genome-related differences in allele size distributions for specific microsatellite loci, but overlap in these distributions among different genomes makes definitive identification and ploidy determination in unisexuals difficult or impossible. Here, we develop the first single nucleotide polymorphism assay for the identification of unisexual biotypes, based on species-specific nucleotide polymorphisms in noncoding DNA loci. Tests with simulated and natural unisexual DNA samples show that this method can accurately identify genome complement and estimate ploidy, making this a valuable tool for assessing the genome composition of unisexual samples. PMID- 22078129 TI - Rizatriptan for treatment of acute migraine in patients taking topiramate for migraine prophylaxis. AB - OBJECTIVE: To assess efficacy and tolerability of rizatriptan orally disintegrating tablet (ODT) for treatment of acute migraine in patients using topiramate for migraine prophylaxis. BACKGROUND: There are limited data from prospective controlled trials demonstrating the benefit of triptans in patients who experience migraine attacks while taking prophylactic medication. METHODS: This was a worldwide, randomized, placebo-controlled, double-blind, multiple attack study in adults with a >1-year history of migraine taking a stable dose of topiramate for migraine prophylaxis and experiencing >=2 moderate/severe attacks per month. Participants treated 3 moderate/severe attacks in crossover fashion (2 with rizatriptan 10-mg ODT, 1 with placebo) following random assignment to 1 of 3 treatment sequences. The primary end point was 2-hour pain relief. RESULTS: Two hour pain relief was significantly greater with rizatriptan compared with placebo (55.0% vs 17.4%, P < .001). Response rates also favored rizatriptan for sustained pain relief from 2-24 hours (32.6% vs 11.1%, P < .001), 2-hour pain freedom (36.0% vs 6.5%, P < .001), normal functional ability at 2 hours (42.2% vs 12.7%, P < .001), and overall treatment satisfaction at 24 hours (60.8% vs 33.6%, P < .001). Few participants reported adverse experiences (16 [15.8%] with rizatriptan, 3 [3.2%] with placebo); none were serious. CONCLUSION: Rizatriptan 10-mg ODT was superior to placebo at all pain end points for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Rizatriptan was generally well tolerated in this population. These results are comparable with those from clinical trials in patients not using prophylaxis, suggesting that the use of topiramate does not affect the efficacy or tolerability of rizatriptan for acute migraine treatment. PMID- 22078128 TI - Diagnosis of chronic conditions with modifiable lifestyle risk factors in selected urban and rural areas of Bangladesh and sociodemographic variability therein. AB - BACKGROUND: Bangladesh suffers from a lack of healthcare providers. The growing chronic disease epidemic's demand for healthcare resources will further strain Bangladesh's limited healthcare workforce. Little is known about how Bangladeshis with chronic disease seek care. This study describes chronic disease patients' care seeking behavior by analyzing which providers diagnose these diseases. METHODS: During 2 month periods in 2009, a cross-sectional survey collected descriptive data on chronic disease diagnoses among 3 surveillance populations within the International Center for Diarrheal Disease Research, Bangladesh (ICDDR, B) network. The maximum number of respondents (over age 25) who reported having ever been diagnosed with a chronic disease determined the sample size. Using SAS software (version 8.0) multivariate regression analyses were preformed on related sociodemographic factors. RESULTS: Of the 32,665 survey respondents, 8,591 self reported having a chronic disease. Chronically ill respondents were 63.4% rural residents. Hypertension was the most prevalent disease in rural (12.4%) and urban (16.1%) areas. In rural areas chronic disease diagnoses were made by MBBS doctors (59.7%) and Informal Allopathic Providers (IAPs) (34.9%). In urban areas chronic disease diagnoses were made by MBBS doctors (88.0%) and IAP (7.9%). Our analysis identified several groups that depended heavily on IAP for coverage, particularly rural, poor and women. CONCLUSION: IAPs play important roles in chronic disease care, particularly in rural areas. Input and cooperation from IAPs are needed to minimize rural health disparities. More research on IAP knowledge and practices regarding chronic disease is needed to properly utilize this potential healthcare resource. PMID- 22078130 TI - New studies in atherosclerosis research. PMID- 22078131 TI - Association between sleep apnea, snoring, incident cardiovascular events and all cause mortality in an adult population: MESA. AB - BACKGROUND: We assessed the association between sleep apnea, snoring, incident cardiovascular (CV) events and all-cause mortality in the Multi Ethnic Study of Atherosclerosis (MESA) cohort. METHODS: Out of 5338 respondents to a sleep questionnaire administered during the second MESA exam period, 208 had physician diagnosed sleep apnea (PDSA), 1452 were habitual snorers (HS) and 3678 were neither a habitual snorer nor had PDSA (normal participants). Cox proportional hazard analysis was used to assess the associations adjusting for age, gender, race/ethnicity, smoking, diabetes mellitus, total cholesterol, HDL, triglycerides, BMI, current alcohol use, benzodiazepine use, BP medications and statin use. RESULTS: Over a 7.5 year average follow-up period, 310 adjudicated CV events including MI, stroke, angina, resuscitated cardiac arrest, stroke death and CVD death and 189 deaths occurred. Compared to HS, PDSA was associated with higher incident CV rates in both univariate and multivariable models [hazard ratio (95%); 1.89 (1.22-2.93), p = 0.004 and 1.91 (1.20-3.04), p = 0.007, respectively]. PDSA was also associated with a higher death rates compared with HS [hazard ratio (95%); 2.13 (1.25-3.63), p = 0.006 and 2.70 (1.52-4.79), p = 0.007, respectively]. Compared with normal participants, PDSA had higher incident CV event rates in both univariate and multivariable models [hazard ratio (95%); 2.23 [1.39-3.60], p = 0.001 and 2.16 [1.30-3.58], p = 0.003, respectively]. Similarly, PDSA had a higher death rate compared with normal participants in both the univariate and multivariable models [hazard ratio (95% CI); 2.44 (1.36-4.37), p = 0.003 and 2.71 (1.45-5.08), p =0 .002, respectively]. Habitual snorers had similar incident CV event rates and death rates in both univariate and multivariable models compared with normal participants. CONCLUSION: PDSA but not habitual snoring was associated with high incident CV events and all-cause mortality in a multi-ethnic population based study of adults free of clinical CV disease at baseline. PMID- 22078132 TI - The role of lactate clearance in the resuscitation bundle. AB - The sepsis resuscitation bundle is the result of an effort on behalf of the Surviving Sepsis Campaign and the Institute for Healthcare Improvement to translate individual guideline recommendations into standardized, achievable goals for physicians caring for the critically ill patient. Implementation of this bundle is associated with decreased mortality. Many of the bundle items reflect components of therapy shown to improve mortality in the seminal early goal-directed therapy trial for severe sepsis and septic shock, including an initial lactate measurement. Elevations in serum lactate are associated with increased mortality, and may result from either increased lactate production or impaired lactate clearance. Lactate clearance may be an important addition to the monitoring and management bundles of patients with severe sepsis and septic shock, However, specific mechanisms of lactate clearance, the relation of lactate clearance to traditional hemodynamic parameters, and the importance of lactate clearance as a therapeutic target or monitoring tool remain unclear. PMID- 22078133 TI - Consciousness versus responsiveness: insights from general anesthetics. PMID- 22078134 TI - Drifting policies are wasting billions. PMID- 22078135 TI - [Management of symptomatic fibroids: role of supracervical hysterectomy and laparoscopy]. AB - OBJECTIVE: Evaluate the relevance of supracervical hysterectomy, in particular by laparoscopy, in the treatment of symptomatic myomas. METHODS: Examination of the literature in the MEDLINE and Cochrane databases, between 1960 and 2010. RESULTS: Because of reduced or identical complications when performed in laparotomy or laparoscopy, respectively, subtotal hysterectomy is a possible alternative to total hysterectomy (grade B). In case of previous or current cervical dysplasy, total hysterectomy is preferable to subtotal hysterectomy (grade B). Conical resection of the endocervix is recommended in case of subtotal hysterectomy (grade C). There is no advantage to subtotal hysterectomy for the sole purpose of avoiding functional or sexual pelvic troubles (grade A). CONCLUSION: In case of symptomatic myomas, subtotal hysterectomy can be beneficial. PMID- 22078136 TI - [Management of post-term pregnancies: the role for AFI, biophysical score and doppler]. AB - OBJECTIVE: To evaluate the role of ultrasound and doppler assessment in the management of prolonged pregnancies and to state its modalities. METHOD: Medline, PubMed, embase and the Cochrane library were searched using terms prolonged pregnancy, post date pregnancy amniotic fluid, ultrasound assessment, doppler, biophysical profile. RESULTS: Single deepest vertical pool measurement is the method of choice of the assessment of amniotic fluid. Indeed, when this method was used, significantly fewer case of oligohydramnios were diagnosed and fewer women had inductions of labor. However, this method is not superior to the amniotic fluid index in the prevention of poor perinatal outcomes. There is a significant difference in the incidence of fetal distress, meconium stained fluid and caesarean section for fetal distress when the amniotic fluid is reduced as compared with normal amniotic fluid. However, sensibility and predictive positive value of oligohydramnios to predict poor perinatal outcomes is moderate. Similary, in most studies, diagnosis of an abnormal uterine, umbilical, aortic or cerebral blood flow doppler was associated with a weak prediction of a poor perinatal outcome. Therefore, we do not recommend its use in management of prolonged pregnancy. There were significantly more diagnosis of oligoamnios and more abnormal antenatal monitoring results in the modified biophysical profile group as compared with the group managed with only single deepest pool but no differences in cord blood gases, neonatal outcome, or in outcomes related to labour and delivery were noted between the two groups. Therefore, biophysical profile including AFI offers no advantage in detecting adverse outcomes and may cause more interventions. CONCLUSION: Close monitoring of fetal condition including assessment of amniotic fluid by single deepest pool twice a week from 41 weeks of gestation is recommended in the management of prolonged pregnancy. Induction of labor could be considered when oligohydramnios is diagnosed by single deepest pool less than 2 cm. PMID- 22078137 TI - [Therapeutic alternatives of uterine fibroids except medicinal treatment and embolization]. AB - OBJECTIVES: To summarize the existing literature on therapeutic alternatives to hysterectomy and myomectomy for management of symptomatic uterine fibroids other than medicinal treatment and embolization. PATIENTS AND METHODS: Pubmed, Cochrane and Embase contents were searched up to December 2010. RESULTS: The Nd:YAG laser appeared to be effective but equipment's cost and postoperative adherence risk limited its development. Bipolar, microwave and cryomyolysis are still investigational. Radiofrequency thermal ablation is a less aggressive alternative when feasible under ultrasound guidance. Focused ultrasound surgery MR or ultrasound guided is accessible to approximately 10% of uterine fibroids with a rate of 60-70% of long-term symptom relief. Data following laparoscopic uterine artery occlusion suggest that outcomes are similar to those with uterine artery embolization (UAE) but with less long-term durability; by transvaginal way, there seem to be more complications. The efficiency of acupuncture remains uncertain. CONCLUSION: Numerous technical innovations have been developed. However, comparative studies with validated conservative options are still needed. PMID- 22078138 TI - [Prolonged pregnancy term and beyond: guidelines for clinical practice - text of the guidelines (short text)]. PMID- 22078139 TI - [Update of myoma management: guidelines for clinical practice - text of the guidelines]. PMID- 22078140 TI - Misoprostol for postpartum hemorrhage: moving from evidence to practice. AB - Clinical and operational evidence indicates that misoprostol is a safe and effective technology for addressing postpartum hemorrhage, a major cause of maternal death. This research has not yet been translated into effective policies, programs, and practice in many parts of the world. Efforts to expand evidence-based use of misoprostol are often complicated by misoprostol's range of indications, insufficient availability, a lack of evidence-based guidelines and provider training, and misconceptions about the drug. The medical and health policy communities need to work together to translate research findings into changes in policy, knowledge, and clinical practice so that we can deliver on the world's promise to improve maternal health. PMID- 22078141 TI - [Superficial acral fibromyxoma: a CD34+ periungual tumor]. PMID- 22078142 TI - [Painless ulcers on the fingers: an unusual presentation of severe bilateral carpal tunnel syndrome]. PMID- 22078143 TI - [Risk factors for basal cell carcinoma: a study from the national dermatology center of Colombia]. AB - BACKGROUND: Colombia is home to one of the areas with the highest levels of exposure to UV radiation in the world, namely, the Andes Mountains, which stretch along the equator. Recent studies have reported an increase in the incidence of basal cell carcinoma in Colombia, but the risk factors associated with the development of this disease have not been studied. OBJECTIVE: To determine the risk factors for basal cell carcinoma in patients from the National Dermatology Center of Colombia. MATERIAL AND METHODS: We performed a case-control study involving 406 individuals, and analyzed sociodemographic, epidemiological, and clinical factors using multiple logistic regression. RESULTS: The following risk factors were identified: skin phototypes I to III (odds ratio [OR], 15.4), family history of skin cancer (OR, 5.8), past history of actinic keratosis (OR, 3.3), continued residence in a rural area after the age of 30 years (OR, 2.96), practice of outdoor sports (OR, 2.67), history of 10 or more episodes of sunburn (OR, 2.3), actinic conjunctivitis (OR, 2.26), and failure to use a hat in childhood (OR, 2.11). CONCLUSIONS: Different factors specific to Colombia increase the risk of basal cell carcinoma. In particular, the association with phototype III could partly explain the increase in incidence detected in this country. Preventive programs should target the risk groups detected and highlight the importance of basing decisions on local evidence. PMID- 22078144 TI - [Correlation between face-to-face assessment and telemedicine for the diagnosis of skin disease in case conferences]. AB - BACKGROUND: In Panama, weekly case conferences are held in which all dermatologists from throughout the country agree on a second opinion for the diagnosis of complicated cases. Unfortunately, patients from the interior of the country may have difficulty attending these case conferences. An alternative in such situations is the use of telemedicine. To date, however, no studies have been undertaken on the effectiveness of this approach in Panama. The aim of this study was to assess the degree of correlation between the diagnoses obtained in case conferences involving face-to-face examination and those involving telemedicine. MATERIAL AND METHOD: A quasi-experimental nonblinded analysis of correlation was carried out in which dermatologists were randomly assigned to 2 groups: face-to-face examination and telemedicine. Both groups were asked to assess 30 cases and the degree of correlation (Cohen kappa coefficient) between the diagnoses made by each group was assessed. RESULTS: The patient group included 19 women (63.3%) and 9 patients (30%) were aged between 50 and 59 years. There was a good correlation (kappa=0.6512) between the results of teledermatology and face-to-face examination. Significant differences in the diagnostic skills of the 2 groups were ruled out. CONCLUSIONS: Teledermatology can be used effectively to facilitate diagnosis in case conferences involving patients who cannot attend in person (gold standard). PMID- 22078145 TI - KI-impregnated oyster shell as a solid catalyst for soybean oil transesterification. AB - Research on inexpensive and green catalysts is needed for economical production of biodiesel. The goal of the research was to test KI-impregnated calcined oyster shell as a solid catalyst for transesterification of soybean oil. Specific objectives were to characterize KI-impregnated oyster shell, determine the effect of reaction variables and reaction kinetics. The catalyst was synthesized by impregnating KI on calcined oyster shells. X-ray diffraction analysis indicated the presence of portlandite and potassium iodide on the surface and a 31-fold increase in surface as a result of calcination and KI impregnation. Under the conditions tested, ideal reaction variables were 1 mmol g(-1) for catalyst loading, 50 degrees C for temperature, 10:1 for methanol/oil, and 4h for reaction time. The transesterification followed a first-order reaction (k=0.4385 h(-1)). The option of using oyster shell for the production of transesterification catalysts could have economic benefits to the aquaculture industry in the US. PMID- 22078146 TI - An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility for the elderly in Oregon. AB - Human metapneumovirus (hMPV) was demonstrated to be responsible for an outbreak of acute respiratory tract infection with high morbidity and mortality among residents of a long-term care facility for the elderly during the late spring summer in Oregon. Respiratory virus infections are a common cause of death in the elderly and the burden of human metapneumovirus may be underestimated. This case report stresses the importance of hMPV in causing outbreaks in long-term care facilities for the elderly. Cough and elevated temperature were common to all the resident patient cases. Six resident patient cases had hMPV laboratory confirmation of which 5 had the diagnosis of pneumonia and 4 were hospitalized. The fatality rate was 33.3% among laboratory confirmed cases and 31.3.0% among probable resident patient cases. The signs and symptoms observed in the elderly with acute respiratory infection caused by hMPV are difficult to distinguish from those associated with other respiratory viruses and direct testing for hMPV with molecular methods should be routinely pursued to prevent nosocomial infections. PMID- 22078147 TI - Cost effectiveness analysis of the New Jersey rapid testing algorithm for HIV testing in publicly funded testing sites. AB - BACKGROUND: Before 2009, New Jersey (NJ) publicly funded counseling and testing sites (CTS) tested for HIV using a single rapid test followed, when positive, by a Western Blot (WB) for confirmation. With this strategy, 74.8% of confirmed positive clients returned to receive test results. To improve the client notification rate at these centers, the New Jersey (NJ) Division of HIV, STD and TB Services (DHSTS) implemented a rapid testing algorithm (RTA) which utilizes a second, different, rapid test to verify a preliminary positive. OBJECTIVE: To compare the cost-effectiveness of the two testing algorithms. STUDY DESIGN: This was a retrospective cost-effectiveness analysis. DATA SOURCES: New Jersey HIV Rapid Testing Support Program (NJHIV) records, DHSTS grant documents, counseling time estimates from an online survey of site supervisors. Costs included test kits and personnel costs from month of RTA implementation through 11/30 in 2008 and 2009. The incremental cost of the RTA was calculated per additional percent of positive clients who were notified and per day earlier notification. RESULTS: In 2008, 215 of 247 clients with a positive rapid HIV test were confirmed positive by WB. 90.9% of clients were notified a mean of 11.4 days after their initial test. 12 refused confirmatory WB. In 2009, 152 of 170 clients with one positive rapid test had a confirmatory second positive rapid test and were notified on the same day. The incremental cost of the RTA was $20.31 per additional positive person notified and $24.31 per day earlier notification or $3.23 per additional positive person and $3.87 per day earlier notification if the WB were eliminated. CONCLUSIONS: The RTA is a cost-effective strategy achieving 100% notification of newly HIV positive clients a mean of 11.4 days earlier compared to standard testing. PMID- 22078148 TI - Molecular characterization of a novel entecavir mutation pattern isolated from a multi-drug refractory patient with chronic hepatitis B infection. AB - BACKGROUND: Prolonged antiviral treatment results in selection and accumulation of resistant strains in quasispecies pool in hepatitis B virus (HBV) infection. OBJECTIVES: The aim of this study was to characterise a novel HBV pattern which shows resistance to lamivudine, adefovir dipivoxil and entecavir using in vitro phenoyping assay. STUDY DESIGN: A male 36 years old patient diagnosed with anti HBe-positive chronic hepatitis B (CHB) had received lamivudine treatment for 7 years following an initial unsuccessfull interferon treatment. The therapy had been switched to adefovir and then to entecavir when breakthrough occcured during each treatment. This led only to a temporary HBV DNA decline which soon was followed by viral breakthrough despite the lack of known entecavir resistance mutations. Patient died after 9 months of entecavir treatment from liver failure. A total of 434 clones from 6 different serum samples were analysed retrospectively. HBV genomes bearing mutation patterns suggestive of antiviral resistance were analysed by in vitro phenotyping assay. RESULTS: Dominance of a clone carrying L80LV, L91I, M204I, S219A, N238D, Y245H changes was detected in the last serum sample of the patient just before his death. This pattern displayed 30.4 fold resistance to entecavir when compared with the wild type HBV by in vitro phenotyping assay. CONCLUSION: A novel mutation pattern showing a high degree of resistance to entecavir was documented. In this pattern, the S219A and Y245H mutations mainly seem to contribute to the emergence of ETV resistance. PMID- 22078150 TI - Impact of ezetimibe coadministered with statins on cardiovascular events following acute coronary syndrome: a 3-year population-based retrospective cohort study in taiwan. PMID- 22078152 TI - Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24 week, randomized, open-label, parallel-group comparison. AB - BACKGROUND: Glycemic excursion is significantly associated with oxidative stress, which plays a role in the development of chronic complications in type 2 diabetes mellitus (T2DM). Acarbose has been reported to reduce cardiovascular risk in patients with impaired glucose tolerance and T2DM. We hypothesize that treatment with acarbose could attenuate glycemic excursions and reduce oxidative stress in patients with T2DM. OBJECTIVE: This study aimed to evaluate the effects of acarbose versus glibenclamide on mean amplitude of glycemic excursions (MAGE) and oxidative stress in patients with T2DM who are insufficiently controlled by metformin. METHODS: T2DM outpatients aged 30 to 70 years who were taking single or dual oral antidiabetic drugs for >=3 months and had a glycosylated hemoglobin (HbA(1c)) value between 7.0% and 11.0% were eligible. Patients were treated with metformin monotherapy (1500 mg daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide add-on for 16 weeks. The dosage of acarbose and glibenclamide was 50 mg TID and 2.5 mg TID, respectively, for the first 4 weeks. In the following 12 weeks, the dosage was doubled in both groups. Continuous glucose monitoring (CGM) for 72 hours and a meal tolerance test (MTT) after a 10 hour overnight fast were conducted before randomization and at the end of study. MAGE was calculated from CGM data. beta-cell response to postprandial glucose increments was assessed by the ratio between incremental AUC of insulin and glucose during MTT. Oxidative stress was estimated by plasma oxidized LDL (ox LDL) and urinary excretion rates of 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)). The primary outcomes included changes in MAGE, plasma ox-LDL, and urinary excretion of 8-iso PGF(2alpha). Adverse events, including hypoglycemia, were recorded. RESULTS: A total of 55 patients were randomized (mean age, 54 years; males, 47%; mean body mass index, 25.9 kg/m(2); mean duration of diabetes, 6.9 years; mean HbA(1c), 8.3%) and 51 patients completed this study (acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P < 0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P < 0.001]). MAGE did not change significantly in glibenclamide treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2alpha) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P < 0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2alpha) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P < 0.01) and serum adiponectin increased (P < 0.05) after treatment with acarbose, whereas HDL-C decreased (P < 0.01) after treatment with glibenclamide. beta-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P < 0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12). CONCLUSIONS: In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729. PMID- 22078153 TI - Impact of a fixed-dose combination of naproxen and esomeprazole magnesium on serum thromboxane B2 inhibition by low-dose aspirin over 5 days in healthy adults: a phase I, randomized, double-blind, placebo-controlled, noninferiority trial. AB - BACKGROUND: Low-dose aspirin (LDA) and nonsteroidal anti-inflammatory drugs (NSAIDs) are often used concomitantly; however, some NSAIDs may interfere with LDA antiplatelet activity. OBJECTIVE: We evaluated the impact of coadministered enteric-coated naproxen 500 mg and immediate-release esomeprazole magnesium 20 mg (fixed-dose combination) on LDA-mediated platelet cyclooxygenase (COX)-1 inhibition. METHODS: In this Phase I, single-center, double-blind, placebo controlled study, healthy volunteers (50-75 years) received enteric-coated LDA 81 mg once daily (QD) on days 1 to 5 (open-label), then enteric-coated LDA 81 mg QD plus either naproxen/esomeprazole magnesium or placebo twice daily (BID) on days 6 to 10 (randomized). Serum thromboxane B(2) (TXB(2)) inhibition from baseline to day 11 was the primary end point. The primary analysis excluded volunteers with <=95% inhibition at day 6. Assay sensitivity and noninferiority of naproxen/esomeprazole magnesium versus placebo were concluded if the 90% CI lower limit for percent inhibition of TXB(2) was >90.0% in both treatment groups (prespecified criterion). Tolerability was a secondary end point. RESULTS: Overall, 42 volunteers were enrolled, 40 randomized, and 32 included in the primary pharmacodynamic analysis (day 6 TXB(2) inhibition >=95%). Most volunteers (86%) were white, and 57% were female. Mean age was 60 (7) years, and mean body mass index was 26.4 (2.6) kg/m(2). Day 11 mean serum TXB(2) inhibition was 99.1% (90% CI, 98.7-99.6) in the LDA plus placebo group (n = 18) versus 99.6% (90% CI, 99.4-99.8) in the LDA plus naproxen/esomeprazole magnesium group (n = 14). Noninferiority of naproxen/esomeprazole magnesium versus placebo was established (CI lower limit >90.0%). Adverse event (AE) incidence was 40% (n = 8/20) in the LDA plus placebo group and 15% (n = 3/20) in the LDA plus naproxen/esomeprazole magnesium group. No serious AEs or discontinuations due to AEs were observed. CONCLUSIONS: This pilot investigation suggests that LDA coadministered with naproxen/esomeprazole magnesium is noninferior to LDA alone for platelet COX-1 inhibition, as measured by serum TXB(2) concentration, in healthy volunteers. ClinicalTrials.gov identifier: NCT01094483. PMID- 22078154 TI - Susceptibility to tigecycline and linezolid among gram-positive isolates collected in the United States as part of the tigecycline evaluation and surveillance trial (TEST) between 2004 and 2009. AB - BACKGROUND: The Tigecycline Evaluation and Surveillance Trial (TEST) was initiated in 2004 to chart the activity of tigecycline and comparator antimicrobial agents against gram-positive and gram-negative organisms globally. OBJECTIVES: This study aimed to provide an analysis of the antimicrobial susceptibility of gram-positive organisms collected from the 9 census regions of the United States between 2004 and 2009. METHODS: The MICs and antimicrobial susceptibility were determined using Clinical and Laboratory Standards Institute methodology. For tigecycline, US Food and Drug Administration susceptibility criteria were used. RESULTS: A total of 8782 Staphylococcus aureus isolates (54.5% methicillin-resistant S aureus) were collected, with the highest percentage of MRSA isolates collected from the South Central region (67.9%). All S aureus isolates were susceptible to tigecycline, linezolid, and vancomycin. Overall, 4.6% of Enterococcus faecalis (n = 3753) and 69.1% of Enterococcus faecium (n = 1417) isolates were vancomycin resistant, with the highest rates in the East North Central region for E faecalis (7.1%) and the South Atlantic region for E faecium (79.5%). Small numbers of linezolid nonsusceptible E faecalis (n = 13) were identified. MIC(90) values for tigecycline were <=0.25 mg/L against E faecalis and 0.12 mg/L against E faecium. Of the Streptococcus pneumoniae isolates collected (n = 4541), 1.1% were penicillin resistant. All S pneumoniae isolates were susceptible to linezolid and vancomycin; susceptibility to tigecycline varied between 80.9% (Pacific region) and 95.2% (West North Central region). CONCLUSIONS: The rates of MRSA and vancomycin-resistant Enterococcus spp varied among the 9 census regions; however, susceptibility to linezolid, vancomycin, and tigecycline remained consistent, with low MIC(90) values and high rates of antimicrobial susceptibility. PMID- 22078155 TI - Pharmacokinetics and tolerability of nasal versus intravenous midazolam in healthy Dutch volunteers: a single-dose, randomized-sequence, open-label, 2 period crossover pilot study. AB - BACKGROUND: Intranasal (IN) midazolam is a potential alternative to rectal diazepam for the acute treatment of epileptic seizures. OBJECTIVE: The purpose of this pilot study was to investigate the pharmacokinetics and tolerability of IN midazolam (50 mg/mL) compared with intravenous (IV) midazolam (2.5 mg) in healthy adult volunteers. METHODS: In this single-dose, randomized-sequence, open-label, 2-period crossover pilot study subjects were randomly assigned to receive IN or IV midazolam, with a washout period of at least 5 days between treatments. The 50 mg/mL IN midazolam formulation consisted of 5 mg midazolam base per 0.1 mL (1 spray) and was administered once in 1 nostril. The IV midazolam solution (2.5 mg) was infused over 10 seconds. Blood samples were taken before and at regular intervals up to 240 minutes after dosing. Pharmacokinetic data (ie, C(max), T(max), t(1/2), and AUC) were analyzed using a 2-compartment model. RESULTS: Of 9 volunteers screened and enrolled, 7 completed the study (mean age 34.1 [9.0] years; mean weight, 68.6 [10.4] kg, range 53-89 kg; 6 men, 3 women; all white). The mean C(max) of 78 (40) ng/mL was reached 44 minutes after IN administration, whereas the mean C(max) was 51 (5) ng/mL after IV administration. The mean estimated C(t=5 min) was 31.4 (28.1) ng/mL after IN administration. The elimination t(1/2) was 1.9 (0.41) hours for IN midazolam and 2.3 (0.19) hours for IV midazolam. The bioavailability of IN midazolam was 82%. There were few adverse events, with a local burning feeling in the nose being the most reported event (6 of 7 subjects). CONCLUSIONS: In this select group of healthy volunteers, concentrations of midazolam >30 ng/mL were reached within 5 minutes of IN administration at a dose of 5 mg/0.1 mL. A burning feeling in the nostril was the main adverse effect. Additional research is needed to evaluate the safety profile, convenience, satisfaction, and efficacy of nasal midazolam in the treatment of adults with seizures. This trial is registered at www.isrctn.org, No. ISRCTN79059168. PMID- 22078156 TI - Removal of osteoid osteoma of the tibia using two-portal posterior ankle arthroscopy. AB - The case of a 30-year-old male with a history of pain in his left ankle is presented. The pain was described as predominantly nocturnal and frequently relieved by the use of nonsteroidal anti-inflammatory drugs. Computed tomography indicated a diagnosis of an osteoid osteoma in the posteromedial portion of the tibia. The patient underwent excision of the tumor using 2-portal posterior ankle arthroscopy. A clearly visualized nidus was removed using a combination of a cochlea and shaver. Histopathologic analysis of the resected tissue confirmed the diagnosis of an osteoid osteoma. The patient reported immediate relief of the pain and was rapidly allowed to bear weight on the foot. During regular follow up, he had no pain recurrence and his joint mobility was normal. To our knowledge, this is the first report of the removal of an osteoid osteoma of the ankle using 2-portal posterior ankle arthroscopy. PMID- 22078157 TI - Diabetic heel ulcer in the Sudan: determinants of outcome. AB - Heel ulceration, on average, costs 1.5 times more than metatarsal ulceration. The aim of this study was to analyze the determinant factors of healing in diabetic patients with heel ulcers and the late outcomes at Jabir Abu Eliz Diabetic Centre Khartoum, Khartoum, Sudan. Data were collected prospectively for 96 of 100 diabetic patients presenting with heel ulcers at the Jabir Abu Eliz Diabetic Centre Khartoum from May 2003 to January 2005. Late outcome was assessed 3 years later (February 2008). Heeling was achieved in one half of the patients (n = 48). In the remaining 48 patients, 22 ended with major lower extremity amputation and 22 were still receiving wound care. A total of 8 patients died, 4 in each group, the healed and unhealed. The most significant determinants of healing using a logistic multivariate regression model, 95% confidence intervals, and odds ratios included a shorter duration of diabetes (p < .009), adequate lower limb perfusion (p < .043), and a superficial foot ulcer (p < .012). Three years later, of the 88 patients who could be traced, 78 were alive and 59 had healed ulcers (7 had died of unrelated causes and 3 of diabetic-related complications), and no additional lower extremity amputation was recorded. Mortality in the series was 18 patients, of whom 14 had undergone a previous lower extremity amputation. Superficial heel ulcers in diabetic patients with a short history of diabetes and with good limb circulation are more likely to heal within an average duration of 25 weeks. At 3 years of follow-up, 75% showed a favorable outcome for ulcer healing, and 22 patients underwent lower extremity amputation (25%), of whom 14 were dead within 3 years. PMID- 22078158 TI - Deep soft tissue leiomyoma mimicking fibromatosis in a 5-year-old male. AB - Leiomyomas of the deep soft tissue in the extremities of children are very rare. These benign soft tissue tumors occur more frequently in adults between the fourth and sixth decades of age. Women are more commonly affected than men, with the uterus the most common location. We present a rare case of deep soft tissue leiomyoma in the foot of a 5-year-old male. The tumor was misdiagnosed as a desmoid-type fibromatosis from the findings of both magnetic resonance imaging and needle biopsy. The unusual age of presentation, atypical location, and failure of magnetic resonance imaging and ultrasound-guided needle biopsy in diagnosing the lesion make the case interesting. The case also highlights the importance of treating such patients at specialist tertiary centers with a multidisciplinary setting. PMID- 22078159 TI - Two patients walk into a clinic...a genomics perspective on the future of schizophrenia. AB - Progress is being made in schizophrenia genomics, suggesting that this complex brain disorder involves rare, moderate to high-risk mutations and the cumulative impact of small genetic effects, coupled with environmental factors. The genetic heterogeneity underlying schizophrenia and the overlap with other neurodevelopmental disorders suggest that it will not continue to be viewed as a single disease. This has radical implications for clinical practice, as diagnosis and treatment will be guided by molecular etiology rather than clinical diagnostic criteria. PMID- 22078160 TI - Impulsivity and pathological gambling: Is it a state or a trait problem? AB - BACKGROUND: This study tested 37 Chinese male pathological gamblers and 40 controls to understand the relationship between pathological gambling and impulsivity as a long-term trait or a short-term state in the cognitive and affective domain. RESULTS: Trait impulsivity was measured by the Barratt Impulsiveness Scale-11. State impulsivity in the cognitive and affective domains were measured by the Stroop Color Word Test and the Emotional Conflict Task, respectively. The pathological gamblers scored significantly higher than the controls on the Barratt Impulsiveness Scale-11. However, there were no significant group differences in performance on the Stroop Color Word Test or the Emotional Conflict Task. CONCLUSIONS: Findings clearly show that pathological gambling is associated with trait but not state impulsivity. In other words, pathological gambling is associated with an impulsivity stemming from enduring personality characteristics that lead gamblers to focus on short-term gains (trait impulsivity) rather than momentary cognitive or affective disinhibition (state impulsivity). Interventions should aim to change pathological gamblers' habitual functioning style by cultivating healthy reflection habits and focusing on long-term rewards. PMID- 22078161 TI - Experimental Study of Cement - Sandstone/Shale - Brine - CO2 Interactions. AB - BACKGROUND: Reactive-transport simulation is a tool that is being used to estimate long-term trapping of CO2, and wellbore and cap rock integrity for geologic CO2 storage. We reacted end member components of a heterolithic sandstone and shale unit that forms the upper section of the In Salah Gas Project carbon storage reservoir in Krechba, Algeria with supercritical CO2, brine, and with/without cement at reservoir conditions to develop experimentally constrained geochemical models for use in reactive transport simulations. RESULTS: We observe marked changes in solution composition when CO2 reacted with cement, sandstone, and shale components at reservoir conditions. The geochemical model for the reaction of sandstone and shale with CO2 and brine is a simple one in which albite, chlorite, illite and carbonate minerals partially dissolve and boehmite, smectite, and amorphous silica precipitate. The geochemical model for the wellbore environment is also fairly simple, in which alkaline cements and rock react with CO2-rich brines to form an Fe containing calcite, amorphous silica, smectite and boehmite or amorphous Al(OH)3. CONCLUSIONS: Our research shows that relatively simple geochemical models can describe the dominant reactions that are likely to occur when CO2 is stored in deep saline aquifers sealed with overlying shale cap rocks, as well as the dominant reactions for cement carbonation at the wellbore interface. PMID- 22078162 TI - The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study. AB - BACKGROUND: The increasing use of highly active antiretroviral therapy (HAART) and pneumococcal immunization along with shifting community exposures may have altered the burden of Streptococcus pneumoniae disease in HIV-infected persons. We describe the burden and risk factors for pneumococcal disease in the modern era of HIV care and evaluate the use of a 23-valent pneumococcal polysaccharide vaccine (PPV-23). METHODS: The incidence of invasive pneumococcal disease (IPD) between January 1st, 2000 and January 1st, 2010 in a regional HIV population in Southern Alberta, Canada was determined by linking comprehensive laboratory and hospital surveillance data. Clinical and epidemiologic data including risk factors for S. pneumoniae, history of pneumococcal immunization, serotypes of infections, and length of any hospitalizations for pneumococcal disease were evaluated with multivariate analysis. CD4 count and viral load at immunization were evaluated with a nested case-control analysis. RESULTS: In 1946 HIV-patients with 11,099 person-years of follow up, there were 68 distinct episodes of pneumococcal disease occurring in 50 patients. Increased risk was seen if female, age >60, Aboriginal ethnicity, lower education, injection drug use, smoking, nadir CD4 <200/MUL, chronic obstructive pulmonary disease, and hepatitis C. Overall, the incidence of IPD was 342/100,000 person-years and was reduced to 187/100,000 within three years of PPV-23 immunization (P < 0.01). Although 78% of patients received PPV-23, 74% of IPD episodes were caused by PPV-23 serotypes. In a case-control analysis, HIV viral load at immunization was significantly predictive of PPV-23 failure, while CD4 count was not. 80% of IPD cases required hospitalization: median length of stay was 7 days (range: 1-71); four patients died. CONCLUSIONS: Despite universal access to intensive measures to prevent pneumococcal disease including the widespread use of HAART and PPV-23 immunization, the incidence of IPD remains high in HIV patients with its associated morbidity and mortality. PMID- 22078163 TI - Turnip yellow mosaic virus forms infectious particles without the native beta annulus structure and flexible coat protein N-terminus. AB - Structural studies have implicated the TYMV N-terminal amino acids of the coat protein (CP) in both static (virion stabilization) and dynamic (RNA encapsidation and disencapsidation) roles. We have deleted residues 2-5, 2-10 and 2-26 from the N-terminus and expressed the mutant CPs in E. coli to assess assembly in the absence of genomic RNA and in plant infections to assess infectivity and virion properties. In E. coli, the deletion constructs formed virus-like particles, but in decreased yield. All mutants were infectious in Chinese cabbage, producing normal symptoms but with a slight delay and decreased viral yields. Virions were progressively less stable with increasing deletion size and also more accessible to small molecules. These results show that the N-terminal 26 amino acids are not essential for viral processes in vivo, although removal of these residues decreases stability and increases porosity, both important factors for virion integrity and survival outside the host. PMID- 22078165 TI - Full genome analysis of a novel adenovirus from the South Polar skua (Catharacta maccormicki) in Antarctica. AB - Adenoviruses have been identified in humans and a wide range of vertebrate animals, but not previously from the polar region. Here, we report the entire 26,340-bp genome of a novel adenovirus, detected by PCR, in tissues of six of nine South Polar skuas (Catharacta maccormicki), collected in Lake King Sejong, King George Island, Antarctica, from 2007 to 2009. The DNA polymerase, penton base, hexon and fiber genes of the South Polar skua adenovirus (SPSAdV) exhibited 68.3%, 75.4%, 74.9% and 48.0% nucleotide sequence similarity with their counterparts in turkey hemorrhagic enteritis virus. Phylogenetic analysis based on the entire genome revealed that SPSAdV belonged to the genus Siadenovirus, family Adenoviridae. This is the first evidence of a novel adenovirus, SPSAdV, from a large polar seabird (family Stercorariidae) in Antarctica. PMID- 22078164 TI - Hepatitis C virus epitope exposure and neutralization by antibodies is affected by time and temperature. AB - A recent study with flaviviruses suggested that structural dynamics of the virion impact antibody neutralization via exposure of ostensibly cryptic epitopes. To determine whether this holds true for the distantly related hepatitis C virus (HCV), whose neutralizing epitopes may be obscured by a glycan shield, apolipoprotein interactions, and the hypervariable region on the E2 envelope protein, we assessed how time and temperature of pre-incubation altered monoclonal antibody (MAb) neutralization of HCV. Notably, several MAbs showed increased inhibitory activity when pre-binding was performed at 37 degrees C or after longer pre-incubation periods, and a corresponding loss-of-neutralization was observed when pre-binding was performed at 4 degrees C. A similar profile of changes was observed with acute and chronic phase sera from HCV-infected patients. Our data suggest that time and temperature of incubation modulate epitope exposure on the conformational ensembles of HCV virions and thus, alter the potency of antibody neutralization. PMID- 22078167 TI - SAS macro programs for geographically weighted generalized linear modeling with spatial point data: applications to health research. AB - An increasing interest in exploring spatial non-stationarity has generated several specialized analytic software programs; however, few of these programs can be integrated natively into a well-developed statistical environment such as SAS. We not only developed a set of SAS macro programs to fill this gap, but also expanded the geographically weighted generalized linear modeling (GWGLM) by integrating the strengths of SAS into the GWGLM framework. Three features distinguish our work. First, the macro programs of this study provide more kernel weighting functions than the existing programs. Second, with our codes the users are able to better specify the bandwidth selection process compared to the capabilities of existing programs. Third, the development of the macro programs is fully embedded in the SAS environment, providing great potential for future exploration of complicated spatially varying coefficient models in other disciplines. We provided three empirical examples to illustrate the use of the SAS macro programs and demonstrated the advantages explained above. PMID- 22078166 TI - Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990-2010. AB - Swine influenza viruses (SIV) have been recognized as important pathogens for pigs and occasional human infections with swine origin influenza viruses (SOIV) have been reported. Between 1990 and 2010, a total of twenty seven human cases of SOIV infections have been identified in the United States. Six viruses isolated from 1990 to 1995 were recognized as classical SOIV (cSOIV) A(H1N1). After 1998, twenty-one SOIV recovered from human cases were characterized as triple reassortant (tr_SOIV) inheriting genes from classical swine, avian and human influenza viruses. Of those twenty-one tr_SOIV, thirteen were of A(H1N1), one of A(H1N2), and seven of A(H3N2) subtype. SOIV characterized were antigenically and genetically closely related to the subtypes of influenza viruses circulating in pigs but distinct from contemporary influenza viruses circulating in humans. The diversity of subtypes and genetic lineages in SOIV cases highlights the importance of continued surveillance at the animal-human interface. PMID- 22078168 TI - Recommendations for the incorporation of biomarkers into Alzheimer clinical trials: an overview. PMID- 22078169 TI - Blood-based biomarkers for Alzheimer's disease: plasma Abeta40 and Abeta42, and genetic variants. AB - Identifying a biomarker for Alzheimer's disease that can be obtained from a blood sample has been a goal of researchers for many years. Over the past few years a number of investigators have studied several plasma biomarkers but most frequently plasma amyloid beta (Abeta)40 and Abeta42 while others have explored the use of genetic variants as biomarkers for diagnosis or risk. This review considers the cross-sectional and longitudinal data regarding plasma Abeta40 and Abeta42 as diagnostic biomarkers as well as risk biomarkers. Review of recent genome-wide association studies indicates as many as 10 genetic variants have been associated with susceptibility to Alzheimer's disease (AD). Further analysis suggests that these factors have modest effects on risk and are thus not helpful, as yet, in the diagnosis of disease. Until the function of these genes is understood, their role in risk and diagnosis will remain uncertain. Thus, there are several types of peripheral biomarkers under investigation, but more work is required before they can be deemed clinically useful. PMID- 22078170 TI - Amyloid imaging as a biomarker for cerebral beta-amyloidosis and risk prediction for Alzheimer dementia. AB - Since the introduction of amyloid imaging nearly 10 years ago, this technique has gained widespread use and acceptance. More recently, published reports have begun to appear in which amyloid imaging is used to detect the effects of antiamyloid therapies. This review will consider the issues involved in the use of amyloid imaging in the development and evaluation of drugs for the treatment of Alzheimer's disease. Current evidence regarding the postmortem correlates of in vivo amyloid imaging data are considered. The application of amyloid imaging to screening subjects for trials and use as an outcome measure is discussed in light of longitudinal changes in the in vivo amyloid signal. While the bulk of this review is directed at symptomatic patients with dementia, consideration is given to the use of amyloid imaging in nondemented subjects as well. Similarities and differences of cerebral amyloid assessment by amyloid imaging and cerebrospinal fluid (CSF) measurements are delineated and an agenda for further research to improve the applicability of amyloid positron emission tomography (PET) to clinical trials is proposed. PMID- 22078171 TI - Potential of functional MRI as a biomarker in early Alzheimer's disease. AB - Functional magnetic resonance imaging (fMRI) is a relative newcomer in the field of biomarkers for Alzheimer's disease (AD). fMRI has several potential advantages, particularly for clinical trials, as it is a noninvasive imaging technique that does not require the injection of contrast agent or radiation exposure and thus can be repeated many times during a longitudinal study. fMRI has relatively high spatial and reasonable temporal resolution, and can be acquired in the same session as structural magnetic resonance imaging. Perhaps most importantly, fMRI may provide useful information about the functional integrity of brain networks supporting memory and other cognitive domains, including the neural correlates of specific behavioral events, such as successful versus failed memory formation. PMID- 22078172 TI - CSF biomarkers for Alzheimer's disease: current utility and potential future use. AB - Over the past 15 years, cerebrospinal fluid (CSF) biomarkers have been shown to be useful for both the diagnosis as well as the prognosis in Alzheimer's disease. It has been shown the CSF levels of amyloid-beta (Abeta)(42) are a very good marker for the presence of amyloid deposition in the brain regardless of clinical status and that total tau and phosphorylated forms of tau are useful in detection of neurodegeneration. When combined together, these CSF markers are useful not only in differential diagnosis but also in predicting conversion and rate of progression from mild cognitive impairment/very mild dementia to more severe impairment. The markers are also useful in predicting conversion from cognitive normalcy to very mild dementia. This field is briefly reviewed and recommendations for future studies in this area are provided. PMID- 22078173 TI - Alliance for aging research AD biomarkers work group: structural MRI. AB - Biomarkers of Alzheimer's disease (AD) are increasingly important. All modern AD therapeutic trials employ AD biomarkers in some capacity. In addition, AD biomarkers are an essential component of recently updated diagnostic criteria for AD from the National Institute on Aging--Alzheimer's Association. Biomarkers serve as proxies for specific pathophysiological features of disease. The 5 most well established AD biomarkers include both brain imaging and cerebrospinal fluid (CSF) measures--cerebrospinal fluid Abeta and tau, amyloid positron emission tomography (PET), fluorodeoxyglucose (FDG) positron emission tomography, and structural magnetic resonance imaging (MRI). This article reviews evidence supporting the position that MRI is a biomarker of neurodegenerative atrophy. Topics covered include methods of extracting quantitative and semiquantitative information from structural MRI; imaging-autopsy correlation; and evidence supporting diagnostic and prognostic value of MRI measures. Finally, the place of MRI in a hypothetical model of temporal ordering of AD biomarkers is reviewed. PMID- 22078174 TI - Changes in cognition. AB - The clinical hallmark of Alzheimer's disease (AD) is a gradual decline in cognitive function. For the majority of patients the initial symptom is an impairment in episodic memory, i.e., the ability to learn and retain new information. This is followed by impairments in other cognitive domains (e.g., executive function, language, spatial ability). This impairment in episodic memory is evident among individuals with mild cognitive impairment (MCI) and can be used to predict likelihood of progression to dementia, particularly in association with AD biomarkers. Additionally, cognitively normal individuals who are likely to progress to mild impairment tend to perform more poorly on tests of episodic memory than do those who remain stable. This cognitive presentation is consistent with the pathology of AD, showing neuronal loss in medial temporal lobe structures essential for normal memory. Similarly, there are correlations between magnetic resonance imaging (MRI) measures of medial temporal lobe structures and memory performance among individuals with mild cognitive impairment. There are recent reports that amyloid accumulation may also be associated with memory performance in cognitively normal individuals. PMID- 22078175 TI - Who attends antenatal care and expanded programme on immunization services in Chad, Mali and Niger? The implications for insecticide-treated net delivery. AB - BACKGROUND: Malaria remains one of the largest public health problems facing the developing world. Insecticide-treated nets (ITNs) are an effective intervention against malaria. ITN delivery through routine health services, such as antenatal care (ANC) and childhood vaccination (EPI), is a promising channel of delivery to reach individuals with the highest risk (pregnant women and children under five years old). Decisions on whether to deliver ITNs through both channels depends upon the reach of each of these systems, whether these are independent and the effectiveness and cost effectiveness of each. Predictors of women attending ANC and EPI separately have been studied, but the predictors of those who attend neither service have not been identified. METHODS: Data from Chad, Mali and Niger demographic and health surveys (DHS) were analyzed to determine risk factors for attending neither service. A conceptual framework for preventative health care seeking behaviour was created to illustrate the hierarchical relationships between the potential risk factors. The independence of attending both ANC and EPI was investigated. A multivariate model of predictors for non-attendance was developed using logistic regression. RESULTS: ANC and EPI attendance were found to be strongly associated in all three countries. However, 47% of mothers in Chad, 12% in Mali and 36% in Niger did not attend either ANC or EPI. Region, mother's education and partner's education were predictors of non-attendance in all three countries. Wealth index, ethnicity, and occupation were associated with non-attendance in Mali and Niger. Other predictors included religion, healthcare autonomy, household size and number of children under five. CONCLUSIONS: Attendance of ANC and EPI are not independent and therefore the majority of pregnant women in these countries will have the opportunity to receive ITNs through both services. Although attendance at ANC and EPI are not independent, delivery through both systems may still add incrementally to delivery through one alone. Therefore, there is potential to increase the proportion of women and children receiving ITNs by delivering through both of these channels. However, modelling is required to determine the level of attendance and incremental potential at which it's cost effective to deliver through both services. PMID- 22078176 TI - [Haemoglobin C/OArab: About a family]. PMID- 22078177 TI - Mucopolysaccharidosis IVA within Tunisian patients: Confirmation of the two novel GALNS gene mutations. AB - Mucopolysaccharidosis type IVA or Morquio A disease is an autosomal recessive disease resulting from a deficiency of the lysosomal enzyme N-acetylgalactosamine 6-sulfate-sulfatase, which hydrolyses N-acetylgalactosamine-6-sulfate and galactose-6-sulfate in glycosaminoglycans. Phenotypes in Morquio A disease vary from the classical form with severe bone dysplasia, heart valve involvement, corneal opacity, short trunk dwarfism and a life span of 20 to 30 years, to attenuated forms with normal life span, mild bone involvement and mild visceral organ involvement. Unlike the other forms of mucopolysaccharidoses, Morquio A disease is characterized by normal intelligence. AIM OF THE STUDY: The aims of this study were to determine if the novel GALNS anomalies IVS1+1G-A and G66R identified in Tunisia are mutations or polymorphisms. PATIENTS AND METHODS: This study was carried out on six Morquio A patients recruited from many regions of Tunisia. We have used SCCP, sequencing and enzymatic digestion. RESULTS: IVS1+1G A and G66R were two deleterious mutations and not polymorphisms. CONCLUSION: Screening of mutations and polymorphisms in GALNS gene provide useful information on genotype/phenotype correlations. It should also facilitate more accurate genetic counselling of newly diagnosed cases and their family members. PMID- 22078178 TI - Effects of gamma irradiation and repetitive freeze-thaw cycles on the biomechanical properties of human flexor digitorum superficialis tendons. AB - An increasing number of tissue banks have begun to focus on gamma irradiation and freeze-thaw in the reconstruction of anterior cruciate ligaments using allografts. The purpose of this study was to evaluate the biomechanical properties of human tendons after exposure to gamma radiation and repeated freeze thaw cycles and to compare them with fresh specimens. Forty flexor digitorum superficialis tendons were surgically procured from five fresh cadavers and divided into four groups: fresh tendon, gamma irradiation, freeze-thaw and gamma irradiation+freeze-thaw. The dose of gamma irradiation was 25 kGy. Each freeze thaw cycle consisted of freezing at -80 degrees C for 7 day and thawing at 25 degrees C for 6 h. These tendons underwent 4 freeze-thaw cycles. Biomechanical properties were analyzed during load-to-failure testing. The fresh tendons were found to be significantly different in ultimate load, stiffness and ultimate stress relative to the other three groups. The tendons of the gamma+freeze-thaw group showed a significant decrease in ultimate load, ultimate stress and stiffness compared with the other three groups. Gamma irradiation and repeated freezing-thawing (4 cycles) can change the biomechanical properties. However, no significant difference was found between these two processes on the effect of biomechanical properties. It is recommended that gamma irradiation (25 kGy) and repetitive freeze-thaw cycles (4 cycles) should not be adopted in the processing of the allograft tendons. PMID- 22078179 TI - Haemodynamic optimisation: are we dynamic enough? AB - Perioperative haemodynamic optimisation of high-risk surgical patients has long been documented to improve both short-term and long-term outcomes, as well as to reduce the rate of postoperative complications. Based on the evidence, cardiac output monitoring and fluid resuscitation, combined with the use of inotropes, would seem to be the gold standard of care for these difficult surgical cases. However, clinicians do not universally apply these techniques and principles in their everyday practice. By exploring the reasons why this is so, perhaps we could move forward in the standardisation of care and the application of evidence based practice. PMID- 22078180 TI - The paradox of disability in abortion debates: bringing the pro-choice and disability rights communities together. PMID- 22078181 TI - Egon R. Diczfalusy, the discovery of the fetoplacental unit and much more. PMID- 22078182 TI - Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide. AB - BACKGROUND: The objective of this analysis was to provide a comprehensive review of ovulation inhibition data of progestins currently available worldwide. This analysis may serve as a reference tool for research on new progestin molecules. STUDY DESIGN: We used literature search engines to detect data of progestin monotherapies on ovulation inhibition in humans. Only treatments with stable dosing during a cycle were accepted. In a second step, we tried to estimate the 99% ovulation inhibiting doses and their fiducial confidence limits using the probit dose-response model. Finally, we analyzed the progestin doses of combined oral contraceptives currently on the market. RESULTS: We found original data on 29 marketed and nonmarketed progestins in a total of 60 publications, published between 1956 and May 2010. Details on methods used for determining ovulation, number of doses and daily dose of each tested progestin, number of subjects, cycles and ovulations are summarized in a table. We designed one example of a dose-response curve using the statistical model. For most progestins, literature data were insufficient for this purpose. A total of 13 progestins are components of oral contraceptives currently on the market worldwide, five of them in combination with 20 mcg ethinyl estradiol (EE). CONCLUSION: This review provides a comprehensive overview of all progestins ever tested for their ovulation inhibition potency and a summary of all preparations currently on the world market, including their regimens and their combinations with EE. PMID- 22078183 TI - Choice of birth control methods among European women and the role of partners and providers. AB - BACKGROUND: The choice of a birth control method is influenced by sociocultural and personal factors. We explored the perceived influences in women's choice of a birth control method in five European countries (Germany, France, the UK, Romania and Sweden), where contraception is widely used. STUDY DESIGN: This is a cross sectional study of 1137 randomly selected women aged 18-49 years. An anonymous, 31-item questionnaire related to birth control methods was used. Logistic regression was used to identify variables associated with partner participation in choice of a contraceptive. RESULTS: Oral contraceptives were mainly used in Germany (54.3%), France (50.5%) and Sweden (34.6%) and condoms in the UK (29.6%) and Romania (22.9%). Sweden showed the highest use of intrauterine devices (IUD, 19%). Romania had the lowest use of contraception. Oral contraceptives and IUDs use were frequently suggested by providers instead of by women. Choosing the method with the partner was associated with age [odds ratio (OR)=0.97, 95% confidence interval (CI) 0.94-0.99], being a university graduate (OR=1.59, 95% CI 1.01-2.29), married (OR=1.52, 95% CI 1.01-2.29) and with using a method that requires partner's cooperation (OR=8.18, 95% CI 5.46-12.27). CONCLUSIONS: Hormonal contraceptives and IUDs are commonly recommended by providers rather than requested by women. Partner preferences are taken into account when his cooperation in the use of the method is needed. As fertility care is a male and female issue, there is still more room for actively involving both women and men in their choice of a birth control method. PMID- 22078184 TI - Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg). AB - BACKGROUND: The efficacy of contraceptives is affected by its route and ease of administration. Herein, both pharmacokinetics and pharmacodynamics of the once-a month combined injectable contraceptive medroxyprogesterone acetate (MPA) plus estradiol cypionate (E(2)-Cyp) were compared after intramuscular (IM) or subcutaneous (SC) injection in women of reproductive age. STUDY DESIGN: Thirty women were randomly assigned to the SC (n=15) or IM (n=15) route of MPA 25 mg+E(2)-Cyp 5 mg administration. Serum samples were obtained daily for 7 days and then three times a week for 40 days in order to quantify E(2), progesterone and MPA. In addition, three ultrasounds were performed on each subject to determine follicular development, and a daily record of the bleeding pattern and side effects was maintained. RESULTS: A comparative analysis showed that the main pharmacokinetic (peak serum concentration, peak serum time, area under the serum concentration vs. time curve, absorption half-life and elimination half-life) and pharmacodynamic parameters, such as follicular development and ovulation, were similar in the SC vs. IM groups. Complete suppression in ovarian function was present in all women. The bleeding patterns and side effects were similar in both groups. CONCLUSIONS: The results presented herein demonstrate that the injection of 25 mg of MPA plus 5 mg of E(2)-Cyp has similar efficacy and safety with either the SC or IM route of administration. The SC option can be considered a viable self-administered contraceptive option that might increase women's compliance to contraceptive use. PMID- 22078185 TI - Comparison of contraceptive method chosen by women with and without a recent history of induced abortion. AB - BACKGROUND: Women undergoing induced abortion may be more motivated to choose long-acting reversible contraception (LARC), including the intrauterine device (IUD) and implant, than women without a history of abortion. Our objective was to determine whether the contraceptive method chosen is influenced by a recent history of induced abortion and access to immediate postabortion contraception. STUDY DESIGN: This was a subanalysis of the Contraceptive CHOICE Project. We compared contraception chosen by women with a recent history of abortion to women without a recent history. Participants with a recent history of abortion were divided into immediate postabortion contraception and delayed-start contraception groups. RESULTS: Data were available for 5083 women: 3410 women without a recent abortion history, 937 women who received immediate postabortion contraception and 736 women who received delayed-start postabortion contraception. Women offered immediate postabortion contraception were more than three times as likely to choose an IUD [adjusted relative risk (RR(adj)) 3.30, 95% confidence interval (CI) 2.67-4.85] and 50% more likely to choose the implant (RR(adj) 1.51, 95%CI 1.12-2.03) compared to women without a recent abortion. There was no difference in contraceptive method selected among women offered delayed-start postabortion contraception compared to women without a recent abortion. CONCLUSION: Women offered immediate postabortion contraception are more likely to choose the IUD and implant than women without a recent abortion history. Increasing access to immediate postabortion LARC is essential to preventing repeat unintended pregnancies. PMID- 22078186 TI - Contraceptive experiences among adolescents who experience unintended birth. AB - BACKGROUND: Adolescents are at high risk of unintended pregnancy due to contraceptive nonuse and inconsistent use. STUDY DESIGN: We examined associations between contraception and mistimed/unwanted birth among adolescents. For contraceptive nonusers, we analyzed factors contributing to unintended birth. RESULTS: Half of adolescents with unintended births did not use contraception at conception. Those ambivalent about pregnancy reported fewer unwanted [relative risk (RR)=0.06] compared to wanted births. Amongst contraceptive nonusers, difficulty accessing birth control was the only factor associated with more unwanted birth (RR=3.05). For Black adolescents, concerns of side effects (RR=7.03), access issues (RR=10.95) and perceived sterility (RR=3.20) were associated with unwanted birth. For younger teens, falsely perceived subfertility increased unwanted birth (RR=2.74), whereas access issues were significant for older teens (RR=3.97). CONCLUSIONS: Access issues and misconceptions around contraceptive side effects and fertility place adolescents at higher risk for unintended pregnancy, especially among younger and Black teens. Ambivalence represents an additional area for intervention. PMID- 22078187 TI - Patients' attitudes and experiences related to receiving contraception during abortion care. AB - BACKGROUND: High risk for additional unintended pregnancies among abortion patients makes the abortion care setting an ideal one for facilitating access to contraception. This study documents attitudes of abortion patients about contraceptive services during their receipt of abortion services and identifies patient characteristics associated with desire for contraception and interest in using a long-acting reversible contraceptive method (LARC). STUDY DESIGN: Structured surveys were administered to 542 patients at five US abortion providing facilities between March and June of 2010. Supplementary information was collected from 161 women who had had abortions in the past 5 years through an online survey. RESULTS: Among abortion patients, two thirds reported wanting to leave their appointments with a contraceptive method and 69% felt that the abortion setting was an appropriate one for receiving contraceptive information. Having Medicaid and having ever used oral contraceptives were predictive of wanting to leave with a method. Women having a second or higher-order abortion were over twice as likely as women having a first abortion to indicate interest in LARC, while black women were half as likely as white women to indicate this interest. CONCLUSION: Many women are interested in learning about and obtaining contraceptive methods, including LARC, in the abortion care setting. PMID- 22078188 TI - A survey of provider experience with misoprostol to facilitate intrauterine device insertion in nulliparous women. AB - BACKGROUND: There is a significant need for research on treatments that provide pain relief during intrauterine device (IUD) insertion. Misoprostol is frequently used before IUD insertion but is not always necessary and its use may increase pain and side effects. This survey evaluated how providers who perform IUD insertion in nulliparous women report using misoprostol to facilitate the procedure. STUDY DESIGN: An anonymous Internet-based survey was distributed to members of three professional organizations with family planning providers. RESULTS: Of 2211 survey respondents, 1905 (86%) reported providing IUDs to nulliparous women. Of those providing IUDs to nulliparous women, 947/1905 (49.7%) reported using misoprostol, and 380 (40%) of 947 of misoprostol users reported using the treatment empirically with all nulliparous IUD insertions. There was wide variation reported in dose, route and timing of misoprostol administration. Providers most commonly reported learning of misoprostol use for IUD insertion by word of mouth rather than through the literature. CONCLUSIONS: Despite conflicting published data, nearly half of survey respondents use misoprostol before IUD insertion. Considerable variation in the timing of misoprostol use may explain differences in perception of its effectiveness. Evidence-based information about misoprostol for IUD insertion in nulliparous women, including pharmacokinetics, efficacy and optimal dosing, is needed. PMID- 22078189 TI - A randomized study of the effect of mifepristone alone or in conjunction with ethinyl estradiol on ovarian function in women using the etonogestrel-releasing subdermal implant, Implanon(r). AB - BACKGROUND: Mifepristone alone or in combination with ethinyl estradiol (EE) can effectively stop an episode of uterine bleeding in women using the etonogestrel releasing contraceptive implant, Implanon(r) but could impair contraceptive efficacy. AIM: To examine the effects of administration of mifepristone alone or with EE on ovarian function and cervical mucus consistency in women using Implanon. STUDY DESIGN: Women using Implanon were randomized to mifepristone 25 mg twice daily on day 1 plus placebo 1 daily for 4 days or plus EE 20 mcg daily for days 2-5. Measurements of serum estradiol (E(2)), progesterone (P(4)), luteinizing hormone (LH), follicle-stimulating hormone (FSH), cervical mucus examination and maximal follicle size (by vaginal ultrasound) were carried out at various times. RESULTS: Following mifepristone intake, there was a dramatic increase in E(2) levels ranging from 543 to 1183 pmol/L (p=.000), which was not correlated with maximal follicle size or preceded by LH or FSH increase. The increase in E(2) triggered an LH increase resulting in development of a luteinized follicle in four women with no evidence of ovulation. One of these women had estradiol and progesterone levels suggestive of ovulation, but no corpus luteum was seen. Almost all women had very low mucus scores, which did not correlate with E(2) levels. DISCUSSION: Despite a transient increase in E(2) levels after mifepristone, there was no evidence of subsequent ovulation irrespective of whether they also received EE. The mechanism by which mifepristone in the presence of etonogestrel results in a rapid increase in E(2) levels remains unclear and could not be related to any significant changes in FSH, LH, ovarian follicle dynamics or subsequent possible ovulation. CONCLUSION: Pregnancy is very unlikely to occur if mifepristone and EE are given during use of Implanon to stop an episode of bleeding. PMID- 22078190 TI - Mifepristone-induced abortion and vaginal bleeding in subsequent pregnancy. AB - BACKGROUND: The aim of this study is to explore the effect of first-trimester mifepristone-induced abortion on vaginal bleeding in subsequent pregnancy. STUDY DESIGN: This observational cohort study was conducted during 1998-2001 at antenatal clinics in Beijing, Chengdu, and Shanghai, China. The study enrolled 4,931 women with one previous mifepristone-induced abortion, 4,925 women with no history of induced abortion, and 4,800 women with one previous surgical abortion and followed them through pregnancy and childbirth. RESULTS: The rates of vaginal bleeding in pregnant women with a history of medical abortion, no abortion, and surgical abortion were 16.5%, 13.9%, and 17.3%, respectively. The women with medical abortion had a higher risk (adjusted relative risk (aRR)=1.17, 95% confidence interval (CI): 1.07, 1.29) of vaginal bleeding compared with those with no abortion but similar risk to prior surgical abortion. When the correlation between medical abortion and vaginal bleeding was examined by period, increased risk was observed only in the early period (<16 gestational weeks) (aRR=1.25, 95% CI: 1.12, 1.39). The comparison between subgroups of medical abortion and no abortion showed that the observed risks increased particularly in those with abortion at gestational age <= 7 weeks (aRR=1.33, 95% CI: 1.18, 1.49), those followed by a postabortion curettage (aRR=1.58, 95% CI: 1.37, 1.84) or complications (aRR=1.99, 95% CI: 1.67, 2.37). There was no difference between women with medical abortion and women with surgical abortion in the occurrence of vaginal bleeding for either period. CONCLUSIONS: One previous mifepristone induced abortion increased the risk of vaginal bleeding in early gestation period of subsequent pregnancy compared with no abortion, especially if abortion occurred before 7 weeks of gestation and was followed by a curettage or complications. PMID- 22078191 TI - Can nurses perform manual vacuum aspiration (MVA) as safely and effectively as physicians? Evidence from India. AB - BACKGROUND: Although legal, access to safe abortion remains limited in India. Given positive experiences of task-shifting from other developing countries, there is a need to explore the feasibility of expanding the manual vacuum aspiration (MVA) provider base to include nurses in India. STUDY DESIGN: A prospective, two-sided equivalence study was undertaken in five facilities of a non-government organisation in Bihar and Jharkhand to explore whether efficacy and safety rates associated with MVA provided by newly trained nurses were equivalent to those provided by physicians. Eight hundred and ninety-seven consenting women with gestation ages of <= 10 weeks were recruited. RESULTS: Nurses were as skilled as physicians in assessing gestation age and completed abortion status, performing MVA and obtaining patient compliance. Overall failure and complication rates were low and equivalent between the two provider types, and both provider types were equally acceptable to women who underwent the procedure (98%). CONCLUSION: Findings of the study make a compelling case for amending existing laws to expand the MVA provider base in order to increase access to safe abortion in India. PMID- 22078192 TI - Menstrual bleeding: perspective of Brazilian women. AB - BACKGROUND: Menstrual patterns, induced amenorrhea and the use of some contraceptive methods which induce non-bleeding are issues under debate among health professionals and women. The objective of the study was to describe perspectives and attitudes of Brazilian women regarding menstruation and its interference in daily activities. STUDY DESIGN: A semistructured questionnaire was applied to nonpregnant, nonlactating women between 18 and 45 years old, who were menstruating, consulting at public health services for other complaints than gynecological or reproductive health care, and staff members and teachers of public universities in one city of each geographic region of Brazil and the Federal District. RESULTS: Of the 885 women interviewed, 51.5% were aged 20-29 years, almost 60% reported normal frequency of bleeding, 22% and 43% reported interference of menstruation in their school activities and in the relationship with their partner, respectively. The value attributed to each interference (<5; >= 5; in a scale up to 10) was >5 for more than 60% of the women in all evaluated domains. The most common reason for disliking menstruation was inconvenient and/or discomfort, and for liking menstruation were feeling healthy and confirmation of not being pregnant. The variables associated to liking menstruation were attending <8 years of school and low economic class, having more than one child and no history of premenstrual tension. CONCLUSION: A great proportion of the interviewed women disliked having menstruation even when they did not present menstrual-related problems. However, some women still preferred monthly menstruation because they felt healthy and it was a free pregnancy test. PMID- 22078193 TI - A prospective double-blinded, randomized, placebo-controlled trial on the use of letrozole pretreatment with misoprostol for second-trimester medical abortion. AB - BACKGROUND: The aim of this randomized trial was to evaluate the abortion rate of combined regimen of letrozole and misoprostol in second-trimester abortion. STUDY DESIGN: This was a randomized, double-blinded, placebo-controlled trial of 130 women requesting legal termination of pregnancy at gestational age between 12 and 20 weeks. Letrozole 7.5 mg or placebo were given for 3 days, followed by misoprostol 400 mcg vaginally every 3 h up to a maximum of five doses on the third day. RESULTS: The abortion rate in 24 and 48 h were similar for the letrozole and placebo groups (24 h: 93.8% vs. 90.8%, respectively, p=.718; 48 h: 98.5% vs. 95.4%, respectively, p=.496). The median induction-to-abortion interval was also similar for the letrozole and placebo groups (9.6 h vs. 10.6 h, p=.145). All the side effects were comparable between the two groups. CONCLUSION: The use of letrozole pretreatment (7.5 mg daily for 3 days) with misoprostol in second trimester abortion does not significantly improve the abortion rate of the misoprostol-only regimen. PMID- 22078194 TI - Oral contraceptive therapy modulates hemispheric asymmetry in spatial attention. AB - BACKGROUND: Functional cerebral asymmetries (FCAs) are known to fluctuate across the menstrual cycle. The visual line-bisection task administered to normally cycling women showed different patterns of the interhemispheric interactions during menses and the midluteal cycle phase. However, the contribution of estrogens and progestins hormones to this phenomenon is still unclear. STUDY DESIGN: The aim of our study was to show a variation of FCAs in women administered oral contraceptives (OCs) using the visual line-bisection task. Visual line-bisection task with three horizontal lines was administered to 36 healthy women taking a 21-day OC. Twenty-nine patients were right handed. The task was administered during OC intake (day 10) and at the end of the pill-free period. RESULTS: The right-handed women showed a significant leftward bias of veridical center on the first and third lines during OC intake compared with an opposite rightward bias during the pill-free period. The same phenomenon of contralateral deviation was observed in left-handed women on day 10 of OC intake. CONCLUSIONS: The results of this study confirm a hormonal modulation on interhemispheric interaction and suggest that OCs may improve the interhemispheric interaction reducing FCAs compared with the low hormone level period. This opens new insights in OC prescription and choice of administration schedule in order to improve cognitive performances. PMID- 22078195 TI - Effect of copper intrauterine device on the cyclooxygenase and inducible nitric oxide synthase expression in the luteal phase endometrium. AB - BACKGROUND: To evaluate the effect of copper intrauterine device (IUD) on the expression of cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS) in the luteal phase endometrium. STUDY DESIGN: A prospective clinical study was conducted on 30 women who were willing to use a copper IUD contraception. Endometrial biopsies and blood samples were taken before and 3 months after the insertion of the IUD on Day 3 and Days 20-24 of the cycle. Main outcome measures were to evaluate the effect of copper IUD on uterine artery blood flow using pulsed color Doppler ultrasonography and the relationship of bleeding abnormalities and menstrual pain level with the uterine blood flow, COX-2 and iNOS expression. RESULTS: Only the left uterine artery pulsatility and resistance indices decreased statistically significantly (p=.005 and p=.039, respectively). Other Doppler parameters showed no change. Cyclooxygenase-2 expression of both endometrial luminal epithelium (p=.03) and gland epithelium (p=.03) increased significantly. Inducible NOS expression of the endometrial surface epithelium decreased significantly after IUD insertion (p=.01). CONCLUSIONS: Although COX-2 expression increased 3 months after copper IUD insertion, iNOS expression of the luminal epithelium decreased. Local hypoxia caused by copper and vasoconstrictor prostanoids may play a role in IUD-related menstrual abnormalities. PMID- 22078196 TI - Serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) inhibits the rat embryo implantation in vivo and interferes with cell adhesion in vitro. AB - BACKGROUND: This study was conducted to observe the in vivo effect of 4-(2 aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) on embryo implantation in rats and its in vitro effect on cell adhesion. STUDY DESIGN: The anti implantation efficacy of AEBSF in rats was determined by counting the number of visible implanted embryos on day 8 of pregnancy following intrauterine (5 mg and 10 mg AEBSF per horn) or tail vein (10 mg AEBSF per rat) administration on day 3 of pregnancy. The effects of AEBSF on cell adhesion were detected, respectively, by using the mouse blastocysts-endometrial cells or the human umbilical vein endothelial cells (HUVECs)-HeLa cells co-culture model. The alteration in protein secretion pattern of HUVECs and HeLa cells was detected by the proteome analysis. RESULTS: 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride showed an in vivo inhibitory effect on embryo implantation in rat. In vitro, AEBSF could disturb the growth of blastocysts on endometrial cells and inhibit the adhesion of HeLa cells on HUVECs. The treatment of AEBSF could alter the protein secretion pattern of co-cultured HUVEC-HeLa cells. CONCLUSION: 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride might be a potential leading compound for novel contraceptives, and its inhibitory effect on implantation might result from the interference in extracellular matrix remodeling process. PMID- 22078197 TI - Etonorgestrel concentrations in morbidly obese women following Roux-en-Y gastric bypass surgery: three case reports. AB - BACKGROUND: Pregnancy should be avoided for 12 to 18 months after Roux-en-Y gastric bypass (RYGB) surgery. The etonorgestrel (ENG)-releasing implant (Implanon(r)) may represent a safe and effective contraceptive method in morbidly obese women who are candidates for bariatric surgery. In addition, the subcutaneous delivery of steroid is unaffected by malabsorptive surgery. METHODS: Three cases of young women with ENG-releasing implant are reported. The device was inserted 1-2 months prior to RYGB. RESULTS: Their initial weights were 130 to 176 kg, and the mean weight loss was 33.6 kg at 6 months. The concomitant serum ENG concentrations decreased currently with weight loss but remained above the minimum concentration required for effective contraceptive effect of the implant for at least 6 months following RYGB (average, 170 pg/mL). The concentrations observed before weight loss were lower than in normal-weight women, but decreases in ENG concentrations following implant insertion were similar. CONCLUSION: These unique data in morbidly obese women highlight the need for further pharmacokinetic studies of contraceptive agents in obese women during weight loss. PMID- 22078198 TI - Response by the leadership of the Society of Assisted Reproductive Technology (SART) to the article "Assisted reproduction and choices in the biotech age". PMID- 22078199 TI - Recognizing existing framework for regulation of assisted reproductive technologies in the United States. PMID- 22078200 TI - Support for more research and evaluation of assisted reproductive technologies. PMID- 22078202 TI - Repeat use of emergency contraception in Kenya: letter to the editor. PMID- 22078204 TI - The impact of out-of-pocket expense on IUD utilization among women with private insurance. AB - BACKGROUND: The study was conducted to evaluate the impact of out-of-pocket expense on intrauterine device (IUD) utilization among women with private insurance. STUDY DESIGN: We reviewed the records of all women with private insurance who requested an IUD for contraception from an urban academic gynecology practice from May 2007 through April 2008. For each patient, we determined the out-of-pocket expense that would be incurred and whether she ultimately had an IUD placed. The total charge for placement of a copper or levonorgestrel IUD (including the device) was $815. RESULTS: Ninety-five women requested an IUD during the study period. The distribution of out-of-pocket expense was bimodal: less than $50 for 35 (37%) women and greater than $500 for 52 (55%) women. Intrauterine device insertion occurred in 24 (25%) women, 19 of whom had an out-of-pocket expense less than $50. In univariate and multivariable analysis, women with insurance coverage that resulted in less than $50 out-of pocket expense for the IUD were more likely to have an IUD placed than women required to pay $50 or more (adjusted odds ratio=11.4, 95% confidence interval=3.6-36.6). CONCLUSIONS: Women requesting an IUD for contraception are significantly more likely to have an IUD placed when out-of-pocket expense is less than $50. PMID- 22078205 TI - Reciprocal coordination of a combination oral contraceptive containing desogestrel+ethinyl estradiol on the expression of LOX-1 and LDLR in placental trophoblast cells. AB - BACKGROUND: The aim of this study was to assess the consistency of antiatherosclerotic potential of a combination oral contraceptive steroid (ethinyl estradiol+desogestrel) by rating its effect on the differential expression of the low-density lipoprotein receptor (LDLR) and lectin-like oxidized LDL (LOX-1) receptor. STUDY DESIGN: Cells from placental trophoblast cell line (JAR) and differentiated primary placental trophoblast cells isolated from term human placentae were used for this study. Expressions of LOX-1 and LDLR were assessed by immunoblot and immunocytochemistry assays. Differential effects of the constituent steroids in the combination of ethinyl estradiol and desogestrel were verified on the expression profile of the receptors. RESULTS: Desogestrel opposed the effect of ethinyl estradiol on LOX-1 expression, and when used in combination, the combination oral contraceptive reduced the expression of LOX-1 in contrast to LDLR. The characteristic change in the expressions of LOX-1 and LDLR showed an antiatherosclerotic improvisation at the unique combination of ethinyl estradiol (10 ng/mL) and desogestrel (20 ng/mL). CONCLUSION: The aforesaid combination of ethinyl estradiol and desogestrel keeps LOX-1 and LDLR reciprocally expressed in antiatherosclerotic mode. PMID- 22078206 TI - What helps the mother of a preterm infant become securely attached, responsive and well-adjusted? AB - OBJECTIVE: To investigate the relationship between the predictor variables of experiential avoidance, relationship satisfaction, prenatal expectations (compared to postnatal experience) and postpartum support, and the criterion variables of maternal attachment, maternal psychological symptoms and maternal responsiveness, after controlling for birth weight. DESIGN: A quantitative survey study. METHOD: The participants were 127 mothers of preterm infants (delivery prior to 37 weeks gestation, <24 months corrected age) recruited through parent support organisations. The web-based survey included measures of: demographics, postpartum support and prenatal expectations (compared to postnatal experience) all designed for this study, as well as maternal attachment, (MPAS) maternal responsiveness (MIRI), experiential avoidance (AAQ), maternal psychological symptoms (DASS-21) and relationship satisfaction (RQI). Three standard multiple regression analyses were conducted. RESULTS: The combined effects of experiential avoidance, relationship satisfaction, prenatal expectations (compared to postnatal experience) and postpartum support accounted for a significant 21% of variance in maternal attachment, Fch (4,121)=8.01, p<.001, a significant 38% of variance in maternal psychological symptoms Fch (4,121)=18.38, p<.001, and a significant 11% of variance in maternal responsiveness, Fch (4,121)=3.78, p=.013 after controlling for birth weight. CONCLUSION: The four predictor variables predicted maternal attachment, psychological symptoms and responsiveness after controlling for birth weight, with experiential avoidance being the most important predictor, followed by prenatal expectations (compared to postnatal experience), relationship satisfaction, then postpartum support. This has implications for designing interventions to optimise attachment and responsiveness, and minimise psychological symptoms, in mothers of infants born preterm. PMID- 22078207 TI - Bee venom protects SH-SY5Y human neuroblastoma cells from 1-methyl-4 phenylpyridinium-induced apoptotic cell death. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by progressive selective loss of dopaminergic neurons in the substantia nigra. Recently, bee venom was reported to protect dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced mice PD model, however, the underlying mechanism is not fully understood. The objective of the present study is to investigate the neuroprotective mechanism of bee venom against Parkinsonian toxin, 1-methyl-4-phenylpyridine (MPP(+)), in SH-SY5Y human neuroblastoma cells. Our results revealed that bee venom pretreatment (1-100 ng/ml) increased the cell viability and decreased apoptosis assessed by DNA fragmentation and caspase-3 activity assays in MPP(+)-induced cytotoxicity in SH SY5Y cells. Bee venom increased the anti-apoptotic Bcl-2 expression and decreased the pro-apoptotic Bax, cleaved PARP expressions. In addition, bee venom prevented the MPP(+)-induced suppression of Akt phosphorylation, and the neuroprotective effect of bee venom against MPP(+)-induced cytotoxicity was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. These results suggest that the anti-apoptotic effect of bee venom is mediated by the cell survival signaling, the PI3K/Akt pathway. These results provide new evidence for elucidating the mechanism of neuroprotection of bee venom against PD. PMID- 22078208 TI - Novel regulatory mechanism and functional implication of plasminogen activator inhibitor-1 (PAI-1) expression in CpG-ODN-stimulated macrophages. AB - Macrophages are activated by recognizing bacterial DNA and CpG oligodeoxynucleotides (CpG-ODNs) through Toll-like receptor-9 (TLR-9). Plasminogen activator inhibitor-1 (PAI-1) has been shown to be an important factor in inflammation-induced macrophage migration which is essential for defense functions. The aim of this study was to demonstrate the molecular mechanism associated with the regulation of PAI-1 expression and its biological significance in CpG-ODN-stimulated mouse macrophages. Our results clearly show that PAI-1 expression in macrophages was highly up-regulated by CpG-ODN stimulation in vitro and in vivo. The TLR-9-mediated stimulation of PAI-1 expression was independent of the NF-kappaB pathway and involved the synergistic activation of Sp1 and Elk-1 by the MEK1/2-ERK and JNK signaling pathways. The elevated PAI-1 expression resulted in significantly enhanced transmigration of RAW264.7 cells through vitronectin but not through fibronectin. We suggest that CpG-ODN plays a role in regulating macrophage migration by stimulating the expression of PAI-1, and the migration is modulated depending on the microenvironmental extracellular matrix components. PMID- 22078210 TI - Expanding the scope of decision-making research for nursing and midwifery practice. AB - Decision making embedded in clinical situations is studied to inform nursing and midwifery practice and to enhance clinical effectiveness. To date this knowledge has mainly been derived from classical decision-making research approaches that are limited in capturing cognition in rapidly changing 'real-world' clinical environments. A naturalistic decision making approach can strengthen the ecological validity of descriptive investigations in certain dynamic clinical decision situations that include urgency and complexity. This paper presents a discussion about naturalistic decision making, its relevance for studying certain clinical decision situations in the 'real world' of nursing and midwifery practice and its application in a midwifery decision-making situation. In conclusion classical decision-making research approaches can be extended to include the naturalistic decision making approach that can capture decision making in dynamic clinical situations and show the underlying knowledge that distinguishes more experienced clinicians. PMID- 22078209 TI - Modulation of CD40-activated B lymphocytes by N-acetylcysteine involves decreased phosphorylation of STAT3. AB - B lymphocyte activation, maturation and reshaping require the interaction of its receptor CD40 with its ligand CD154, which is expressed on activated T lymphocytes. Metabolism in activated B lymphocytes is also characterized with several REDOX changes including fluctuation of Reactive Oxygen Species (ROS). Herein, we first confirm that stimulation of human peripheral blood B lymphocyte with CD154 increases intracellular ROS level. Then, by treatments with two well known antioxidants, N-acetylcysteine (NAC) and Trolox, we further investigate the influence of REDOX fluctuation in CD40-activated B lymphocyte homeostasis in long term culture (13 days). Treatments with NAC increase viability, decrease proliferation and Ig secretion and enhance homoaggregation of B lymphocytes while Trolox only induces a marginal increase of their Ig secretion. The NAC-induced homoaggregation phenotype is paralleled with increased expressions of CD54, CD11a, CD27 and CD38. Mechanistically, a 24h exposure of B lymphocytes with NAC is sufficient to show strong inhibition of STAT3 phosphorylation. Besides, the treatment of B lymphocytes with the STAT3 inhibitor VI increases viability and decreases proliferation and secretion as in NAC-treated cells thus showing a role for STAT3 in these NAC-induced phenotypes. This study done in a human-based model provides new findings on how REDOX fluctuations may modulate CD40-activated B lymphocytes during immune response and provide additional hints on NAC its immunomodulatory functions. PMID- 22078211 TI - Tools for measuring the impact of informal caregiving of the elderly: a literature review. AB - OBJECTIVES: (1) Describe available tools to assess the impact of informal caregiving of home-dwelling elderly, (2) identify an acceptable and appropriate tool for a study aiming at the evaluation of the impact of innovative projects for care and support of care for elderly at home, on their main informal caregiver and (3) find a definition of 'main informal caregiver'. STUDY DESIGN: Literature review by searches of the following electronic databases: MEDLINE, CINAHL, EMBASE, using firstly keywords and exclusion criteria, then citations and reference search. RESULTS: This review has identified 105 scales assessing the impact of informal caregiving of the elderly. Those scales were described in terms of characteristics of the care receiver population, content and psychometric properties. Most retrieved scales are intended to measure the impact of caregiving on caregivers' health of elderly with dementia (n=49), overall elderly (n=21), cancer patients (n=7), chronically ill patients (n=7), psychiatric patients (n=7) and stroke patients (n=3). Dimensions of the impact of caregiving were classified into its positive (n=34), negative (n=55) or neither positive nor negative (n=16) consequences on the informal caregiver's health. Internal consistency varied from 0.48 to 0.99 and in half of the cases (n=52), construct validity was reported. Scales comprised 1-200 questions. The Zarit Burden Interview (ZBI-12) was selected for the study and an operational definition of the concept of "main informal caregiver" was constructed. CONCLUSION: This review identified a large number of scales that can be used to assess the impact of caregiving, viewed through different dimensions. The Zarit Burden Interview can be a useful tool for researchers and clinicians due to its user-friendliness, extensively validation and international use, making comparisons between groups possible. Despite the fact that only the original version of each scale was selected, this inventory should be a useful tool for intervention studies and even clinicians work. PMID- 22078212 TI - Challenges in transition from intervention to end of life care in intensive care: a qualitative study. AB - BACKGROUND: Providing quality end of life care is a challenging area in intensive care practice. The most demanding aspect for doctors and nurses in this setting is not the management of care at end of life per se, but facilitating the transition from active intervention to palliation and finally, end of life care. Whilst there is understanding about some aspects of this transition, recognition of the complex and inter-related processes that work to shift the patient's trajectory from cure to end of life care is required. This is important in order to work towards solutions for issues that continue to pose problems for health care professionals. OBJECTIVES: To identify the challenges for health care professionals when moving from a recovery trajectory to an end of life trajectory in intensive care. DESIGN: Qualitative methods of enquiry. METHODS AND SETTING: Single semi-structured interviews with 13 medical staff and 13 nurses associated with 17 decedents who underwent treatment withdrawal in intensive care were carried out. Participants were drawn from two Intensive Care Units in a large university-affiliated hospital in England. FINDINGS: Patients who died in intensive care appeared to follow a three-stage end of life trajectory: admission with hope of recovery; transition from intervention to end of life care; a controlled death. The transition from intervention to end of life care was reported as being the most problematic and ambiguous stage in the end of life trajectory, with potential for conflict between medical teams, as well as between doctors and nurses. CONCLUSIONS: End of life care policy emphasises the importance of end of life care for all patients regardless of setting. These findings demonstrate that in intensive care, there is need to focus on transition from curative intervention to end of life care, rather than end of life care itself so that effective and timely decision making underpins the care of the 20% of intensive care patients who die in this setting each year. PMID- 22078213 TI - Synthesis and evaluation of a novel (99m)Tc-labeled bioreductive probe for tumor hypoxia imaging. AB - Tumor hypoxia is closely associated with the malignant progression and/or the high metastatic ability of tumors and often induces resistance to chemo- and/or radiotherapy. Thus, the detection and evaluation of hypoxia is important for the optimization of cancer therapy. We designed a novel (99m)Tc-labeled probe for tumor hypoxia imaging that utilizes bioreductive reactions in hypoxic cells. This probe, which contains a 4-nitrobenzyl ester group, is reduced in hypoxic cells to produce a corresponding carboxylate anion that cannot penetrate cell membranes because of its hydrophilicity and negative charge; therefore, it is expected to be trapped inside hypoxic cells. Based on this unique strategy, we synthesized the Technetium-99m ((99m)Tc)-labeled probe (99m)Tc-SD32. The uptake of (99m)Tc SD32 in tumor cells was investigated under normoxic and hypoxic conditions. (99m)Tc-SD32 showed sufficient accumulation and good retention in hypoxic cells. In addition, we demonstrated that (99m)Tc-SD32 was subjected to bioreduction in hypoxic cells and was trapped as the corresponding carboxylate anion. These results indicated that (99m)Tc-SD32 would be a promising agent for in vivo hypoxia imaging. PMID- 22078214 TI - Synthesis and SAR development of novel P2X7 receptor antagonists for the treatment of pain: part 2. AB - Novel P2X(7) antagonists were developed using a purine scaffold. These compounds were potent and selective at the P2X(7) receptor in human and rodent as well as efficacious in rodent pain models. Compound 15a was identified to have oral potency in several pain models in rodent similar to naproxen, gabapentin and pregabalin. Structure-activity relationship (SAR) development and results of pain models are presented. PMID- 22078215 TI - Biaryl analogues of teriflunomide as potent DHODH inhibitors. AB - The structure-activity relationships of a novel series of biaryl dihydroorotate dehydrogenase (DHODH) inhibitors related to teriflunomide are disclosed. These biaryl derivatives were the result of structure-based design and proved to be potent DHODH inhibitors which in addition showed good antiproliferative activities on peripheral blood mononuclear cells and good efficacies in vivo in the rat adjuvant-induced-arthritis model. PMID- 22078216 TI - 2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes. AB - The present study describes a novel series of ATP-competitive PKC inhibitors based on the 2,6-naphthyridine template. Example compounds potently inhibit the novel Protein Kinase C (PKC) isotypes delta, epsilon, eta, theta (in particular PKCepsilon/eta, and display a 10-100-fold selectivity over the classical PKC isotypes. The prototype compound 11 was found to inhibit PKCtheta-dependent pathways in vitro and in vivo. In vitro, a-CD3/a-CD28-induced lymphocyte proliferation could be effectively blocked in 10% rat whole blood. In mice, 11 dose-dependently inhibited Staphylococcus aureus enterotoxin B-triggered IL-2 serum levels after oral dosing. PMID- 22078217 TI - Chronic pain in older adults: a controlled pilot trial of a brief cognitive behavioural group treatment. AB - BACKGROUND: Chronic pain is a common condition among older adults. While cognitive behaviour therapy (CBT) has been tested in numerous studies on adults and children there are fewer studies on older persons. The objective of this study was to investigate the effects of a six-session CBT group treatment for older persons with chronic pain. As a secondary aim we investigated whether treatment credibility was associated with outcome. METHOD: We included 21 persons (mean age = 72.0 years) who were randomly allocated to either a waitlist condition or treatment consisting of applied relaxation, with the addition of problem solving, assertiveness, communication strategies, sleep management, and relapse prevention. RESULTS: Few statistically significant effects were found on measures of pain, mood, anxiety, and quality of life; however, a significant treatment effect with a between group effect size of d = 1.0 was observed with respect to perceived ability to function despite the discomfort of pain. CONCLUSION: The study provides some preliminary support for the use of group based CBT with a focus on applied relaxation for older adults with chronic pain. PMID- 22078218 TI - Outcome after repair of cor triatriatum. AB - Cor triatriatum represents <0.1% of all congenital cardiac malformations. Symptoms in patients with cor triatriatum are related to pulmonary venous obstruction and pressure loading of the right side of the heart. The aim of this study was to describe our institutional experience with repair of cor triatriatum. From June 1963 to June 2010, 65 patients underwent repair at a median age of 7.2 months (range 2 days to 47.6 years). Among these patients, 49 (75%) had associated congenital heart defects. Atrial septal defect (n = 29), ventricular septal defect (n = 15), partially or totally anomalous pulmonary venous return (n = 14), mitral valve abnormalities (n = 11), and supravalvar mitral ring (n = 5) were the most common associated defects. Surgical treatment consisted of excision of the membrane, along with additional procedures in 47 patients (72%). Five patients had new postoperative supraventricular arrhythmias. During a median follow-up period of 5.4 years, no patients underwent reintervention for recurrent left atrial obstruction, 7 patients were noted to have minor residual cor triatriatum without obstruction, and 8 patients (including 4 diagnosed before cor triatriatum repair) had pulmonary vein stenosis, 6 of whom underwent intervention for that reason. In conclusion, in this large surgical series of patients who underwent repair of cor triatriatum, there were no cases of significant residual or recurrent cor triatriatum. Although the association between cor triatriatum and pulmonary vein stenosis has been described previously, the relative frequency of this condition in our cohort (>10%, including patients diagnosed before and after cor triatriatum repair) is noteworthy. Abnormalities of the mitral valve and a supravalvar mitral ring were also seen more often than the existing research would suggest, which may be another important consideration in evaluating and following these patients. PMID- 22078219 TI - Association of myocardial fibrosis, B-type natriuretic peptide, and cardiac magnetic resonance parameters of remodeling in chronic ischemic cardiomyopathy. AB - The left ventricular (LV) scar size detected by cardiac magnetic resonance (CMR) imaging in ischemic cardiomyopathy (IC) has been correlated with mortality. However, the associations among myocardial fibrosis, ventricular geometry, and physiologic measures of myocardial performance remain to be defined. A retrospective analysis of patients with stable chronic IC (LV ejection fraction <=50%) who underwent CMR imaging from 2004 to 2010 and had plasma B-type natriuretic peptide (BNP) measured within 14 days of the CMR study was undertaken. A total of 38 patients met the criteria (mean age 66 +/- 10 years; 31 men [82%]). The duration of IC was 67 +/- 69 months. The CMR characteristics included LV dilation (LV end-diastolic dimension 62 +/- 8 mm) and severe systolic dysfunction (LV ejection fraction 28 +/- 11%). The average quantitated myocardial fibrosis was 20 +/- 12% of the LV mass. When stratified by fibrotic mass, increased myocardial scar size was associated with increased LV cavity size (p = 0.007), lower LV ejection fraction (p = 0.04), and higher BNP (p = 0.013). In comparison, when stratified by median BNP (475 pg/ml), an elevated BNP level was associated, not only with LV size, function, and degree of fibrosis, but also with increased meridional wall stress (p = 0.002) and worse New York Heart Association functional class (p = 0.006). In conclusion, in chronic IC, quantitated myocardial fibrosis is associated with CMR structural and functional LV abnormalities. Elevated BNP levels are related to high-risk structural and functional CMR abnormalities and wall stress and functional status. Myocardial fibrosis appears to be related to plasma BNP through the processes of ventricular remodeling. PMID- 22078220 TI - Analysis of echocardiograms in a large heterogeneous cohort of patients with friedreich ataxia. AB - Although Friedreich ataxia (FA) is associated with cardiomyopathy, the severity and evolution of cardiac disease is poorly understood. To identify factors predicting cardiomyopathy in FA, we assessed echocardiograms from a large heterogenous cohort and their relation to disease traits. The most recent echocardiograms from 173 subjects with FA were analyzed in a core laboratory to determine their relation to disease duration, subject age, age of onset, functional disability score, and GAA repeat length. Mean age of the cohort was 19.7 years, mean age of disease onset was 10.6 years, and mean shorter GAA length was 681 repeats. Echocardiograms collectively illustrated systolic dysfunction, diastolic dysfunction, and hypertrophy. Measurements of hypertrophy correlated moderately with each other (r = 0.39 to 0.79) but not with measurements of diastolic dysfunction (r <0.35). Diastolic measurements correlated poorly with each other, although 26% of the cohort had multiple diastolic abnormalities. The most common diastolic dysfunction classification was pseudonormalization. Classification of diastolic dysfunction was predicted by GAA repeat length but not by age or gender. Ejection fraction was below normal in 20% of the cohort. In linear regression analysis, increasing age predicted decreasing ejection fraction. Functional disability score, a measurement of neurologic ability, did not predict any echocardiographic measurements. In conclusion, hypertrophy and diastolic and systolic dysfunctions occur in FA and are substantially independent; diastolic dysfunction is the most common abnormality with most patients having an assigned diastolic dysfunction class of pseudonormalization. PMID- 22078221 TI - Comparison of incidence of bleeding and mortality of men versus women with ST elevation myocardial infarction treated with fibrinolysis. AB - Gender-related differences in the incidence of bleeding and its relation to subsequent mortality in patients with ST-segment elevation myocardial infarction (STEMI) treated with fibrinolysis are not well understood. We studied patients with STEMI receiving fibrinolysis enrolled in 6 clinical trials. Outcomes included moderate or severe bleeding defined using Global Utilization of Strategies to Open Occluded Arteries (GUSTO) criteria and adjusted 1-year mortality (excluding deaths in first 24 hours). Moderate or severe bleeding was 1.9-fold higher in women compared to men (13.3% vs 7.1%, p <0.0001). Bleeding remained higher in women even after adjustment for baseline differences (odd ratios 1.52, 95% confidence interval [CI] 1.42 to 1.62). In fact, female gender was second most important prognostic factor (Wald chi-square 153.6) after older age (Wald chi-square 241.2) in the multivariable bleeding model. Overall 1-year mortality was similar in women and men after adjusting for prognostically important baseline differences (hazard ratio [HR] 1.06, 95% CI 0.97 to 1.17). However, after adjustment for baseline confounders and bleeding, female gender was associated with a lower risk of 1-year death. Thus, adjusted 1-year mortality was similar in women compared to men without bleeding (HR 1.08, 95% CI 0.97 to 1.19) but lower in women compared to men with bleeding (HR 0.85, 95% CI 0.73 to 0.98, p for interaction of gender by bleeding = 0.0016). The highest adjusted 1 year mortality was observed in men with bleeding (HR 2.42, 95% CI 2.20 to 2.66) followed by women with bleeding (HR 2.05, 95% CI 1.80 to 2.33) and women without bleeding (HR 1.08, 95% CI 0.97 to 1.19, referent men without bleeding). In conclusion, in patients with fibrinolytic-treated STEMI, women had a higher incidence but lower mortality with bleeding than men. These data highlight the importance of understanding factors associated with gender-related differences in bleeding and represent an opportunity for improving outcomes of women and men with fibrinolytic-treated STEMI. PMID- 22078223 TI - Trauma networks: present and future challenges. AB - In England, trauma is the leading cause of death across all age groups, with over 16,000 deaths per year. Major trauma implies the presence of multiple, serious injuries that could result in death or serious disability. Successive reports have documented the fact that the current ad hoc unstructured management of this patient group is associated with considerable avoidable death and disability. The reform of trauma care in England, especially of the severely injured patient, has already begun. Strong clinical leadership is embraced as the way forward. The present article summarises the steps that have been made over the last decade that led to the recent decision to move towards a long anticipated restructure of the National Health Service (NHS) trauma services with the introduction of Regional Trauma Networks (RTNs). While, for the first time, a genuine political will and support exists, the changes required to maintain the momentum for the implementation of the RTNs needs to be marshalled against arguments, myths and perceptions from the past. Such an approach may reverse the disinterest attitude of many, and will gradually evolve into a cultural shift of the public, clinicians and policymakers in the fullness of time. PMID- 22078222 TI - Monophosphorylation of CD79a and CD79b ITAM motifs initiates a SHIP-1 phosphatase mediated inhibitory signaling cascade required for B cell anergy. AB - Anergic B cells are characterized by impaired signaling and activation after aggregation of their antigen receptors (BCR). The molecular basis of this impairment is not understood. In studies reported here, Src homology-2 (SH2) containing inositol 5-phosphatase SHIP-1 and its adaptor Dok-1 were found to be constitutively phosphorylated in anergic B cells, and activation of this inhibitory circuit was dependent on Src-family kinase activity and consequent to biased BCR immunoreceptor tyrosine-based activation motif (ITAM) monophosphorylation. B cell-targeted deletion of SHIP-1 caused severe lupus-like disease. Moreover, absence of SHIP-1 in B cells led to loss of anergy as indicated by restoration of BCR signaling, loss of anergic surface phenotype, and production of autoantibodies. Thus, chronic BCR signals maintain anergy in part via ITAM monophosphorylation-directed activation of an inhibitory signaling circuit involving SHIP-1 and Dok-1. PMID- 22078224 TI - Consistent Differential Expression Pattern (CDEP) on microarray to identify genes related to metastatic behavior. AB - BACKGROUND: To utilize the large volume of gene expression information generated from different microarray experiments, several meta-analysis techniques have been developed. Despite these efforts, there remain significant challenges to effectively increasing the statistical power and decreasing the Type I error rate while pooling the heterogeneous datasets from public resources. The objective of this study is to develop a novel meta-analysis approach, Consistent Differential Expression Pattern (CDEP), to identify genes with common differential expression patterns across different datasets. RESULTS: We combined False Discovery Rate (FDR) estimation and the non-parametric RankProd approach to estimate the Type I error rate in each microarray dataset of the meta-analysis. These Type I error rates from all datasets were then used to identify genes with common differential expression patterns. Our simulation study showed that CDEP achieved higher statistical power and maintained low Type I error rate when compared with two recently proposed meta-analysis approaches. We applied CDEP to analyze microarray data from different laboratories that compared transcription profiles between metastatic and primary cancer of different types. Many genes identified as differentially expressed consistently across different cancer types are in pathways related to metastatic behavior, such as ECM-receptor interaction, focal adhesion, and blood vessel development. We also identified novel genes such as AMIGO2, Gem, and CXCL11 that have not been shown to associate with, but may play roles in, metastasis. CONCLUSIONS: CDEP is a flexible approach that borrows information from each dataset in a meta-analysis in order to identify genes being differentially expressed consistently. We have shown that CDEP can gain higher statistical power than other existing approaches under a variety of settings considered in the simulation study, suggesting its robustness and insensitivity to data variation commonly associated with microarray experiments. AVAILABILITY: CDEP is implemented in R and freely available at: http://genomebioinfo.musc.edu/CDEP/. CONTACT: zhengw@musc.edu. PMID- 22078225 TI - The impact of bromide/iodide concentration and ratio on iodinated trihalomethane formation and speciation. AB - The objective of this study was to evaluate the formation and speciation of iodinated trihalomethanes (I-THMs) from preformed chloramination of waters containing bromide (Br(-)) and iodide (I(-)) at a Br(-)/I(-) weight ratio of 10:1. The factors investigated were pH, iodide to dissolved organic carbon (I( )/DOC) ratio, and NOM characteristics, specifically SUVA(254). A Br(-)/I(-) ratio of 1:2 was also evaluated to determine the importance of Br(-) and I(-) concentrations and ratio on I-THM formation and speciation. Regulated triholamethanes (THMs) were measured alongside I-THMs for a more complete understanding of trihalomethane formation. The results showed that, in general, both I-THM and THM formation increased with decreased pH. Greater formation at lower pH was likely attributed to monochloramine decomposition and the formation of additional oxidants and substituting agents, most notably chlorine. For pH >= 7.5, I-THM yield increased with increasing I(-)/DOC ratio and decreasing specific ultraviolet absorbance (SUVA(254)) of the water. The Br(-)/I(-), Br(-)/DOC and I( )/DOC ratios were important factors for I-THM and THM speciation. At pH 6, dichloroiodomethane (CHCl(2)I) and bromochloroiodomethane (CHBrClI) were the dominant species at the common bromide and iodide levels. For pH >= 7.5 and for elevated bromide and iodide levels, iodoform (CHI(3)) was always the dominant specie regardless of the Br(-)/I(-) ratio. The results demonstrated that it is important to examine I-THM formation and speciation at typical Br(-)/I(-) ratios (~ 10) of natural waters, which have often been overlooked in previous investigations, in order to obtain practical and relevant results. PMID- 22078226 TI - Recycled water: potential health risks from volatile organic compounds and use of 1,4-dichlorobenzene as treatment performance indicator. AB - Characterisation of the concentrations and potential health risks of chemicals in recycled water is important if this source of water is to be safely used to supplement drinking water sources. This research was conducted to: (i) determine the concentration of volatile organic compounds (VOCs) in secondary treated effluent (STE) and, post-reverse osmosis (RO) treatment and to; (ii) assess the health risk associated with VOCs for indirect potable reuse (IPR). Samples were examined pre and post-RO in one full-scale and one pilot plant in Perth, Western Australia. Risk quotients (RQ) were estimated by expressing the maximum and median concentration as a function of the health value. Of 61 VOCs analysed over a period of three years, twenty one (21) were detected in STE, with 1,4 dichlorobenzene (94%); tetrachloroethene (88%); carbon disulfide (81%) and; chloromethane (58%) most commonly detected. Median concentrations for these compounds in STE ranged from 0.81 MUg/L for 1,4-dichlorobenzene to 0.02 MUg/L for carbon disulphide. After RO, twenty six (26) VOCs were detected, of which 1,4 dichlorobenzene (89%); acrylonitrile (83%) chloromethane (63%) and carbon disulfide (40%) were the more frequently detected. RQ(max) were all below health values in the STE and after RO. Median removal efficiency for RO was variable, ranging from -77% (dichlorodifluoromethane) to 91.2% (tetrachloroethene). The results indicate that despite the detection of VOCs in STE and after RO, their human health impact in IPR is negligible due to the low concentrations detected. The results indicate that 1,4-dichlorobenzene is a potential treatment chemical indicator for assessment of VOCs in IPR using RO treatment. PMID- 22078227 TI - Boron bioremoval by a newly isolated Chlorella sp. and its stimulation by growth stimulators. AB - It has been well documented that excess concentrations of boron (B) causes toxic effects on many of the environmental systems. Although Chlorella sp. has been studied to remove pollutants from water, its capacity to remove B has not been investigated yet. Boron removal levels of newly isolated Chlorella sp. were investigated in BG 11 media with stimulators as triacontanol (TRIA) and/or sodium bicarbonate (NaHCO(3)) and without them, to test if they could increase the removal efficiency by increasing biomass. The assays were performed to determine the effect of different medial compositions, B concentrations, pH and biomass concentrations onto removal efficiency. Boron removal was investigated at 5-10 mg/L range at pH 8 in different medial compositions and maximum removal yield was found as 32.95% at 5.45 mg/L B in media with TRIA and NaHCO(3). The effect of different pH values on the maximum removal yield was investigated at pH 5-9, and the optimum pH was found again 8. The interactive effect of biomass concentration and B removal yield was also investigated at 0.386-1.061 g wet weight/L biomass. The highest removal yield was found as 38.03% at the highest biomass range. This study highlights the importance of using new isolate Chlorella sp. as a new biomaterial for B removal process of waters containing B. PMID- 22078228 TI - Effect of moderate pre-oxidation on the removal of Microcystis aeruginosa by KMnO4-Fe(II) process: significance of the in-situ formed Fe(III). AB - This study developed a novel KMnO(4)-Fe(II) process to remove the cells of Microcystis aeruginosa, and the mechanisms involved in have been investigated. At KMnO(4) doses of 0-10.0 MUM, the KMnO(4)-Fe(II) process showed 23.4-53.3% higher efficiency than the KMnO(4)-Fe(III) process did. This was first attributed to the moderate pre-oxidation of M. aeruginosa by KMnO(4), achieved by dosing Fe(II) after a period of pre-oxidation, to cease the further release of intracellular organic matter (IOM) and the degradation of dissolved organic matter (DOM). The extensive exposure of M. aeruginosa to KMnO(4) in KMnO(4)-Fe(III) process led to high levels and insufficient molecular weight of DOM, inhibiting the subsequent Fe(III) coagulation. Additionally, Fe(II) contributed to lower levels of the in situ formed MnO(2), the reduction product of KMnO(4) which adversely affected algae removal by Fe(III) coagulation. However, the in-situ formed Fe(III), which was derived from the oxidation of Fe(II) by KMnO(4), in-situ MnO(2), and dissolved oxygen, dominated the remarkably high efficiency of KMnO(4)-Fe(II) process with respect to the removal of M. aeruginosa. On one hand, in-situ formed Fe(III) had more reactive surface area than pre-formed Fe(III). On the other hand, the continuous introduction of fresh Fe(III) coagulant showed higher efficiency than one-off dosage of coagulant to destabilize M. aeruginosa cells and to increase the flocs size. Moreover, the MnO(2) precipitated on algae cell surfaces and contributed to the formation of in-situ formed Fe(III), which may act as bridges to enhance the removal of M. aeruginosa. PMID- 22078229 TI - Microscale geochemical gradients in Hanford 300 Area sediment biofilms and influence of uranium. AB - The presence and importance of microenvironments in the subsurface at contaminated sites were suggested by previous geochemical studies. However, no direct quantitative characterization of the geochemical microenvironments had been reported. We quantitatively characterized microscale geochemical gradients (dissolved oxygen (DO), H(2), pH, and redox potential) in Hanford 300A subsurface sediment biofilms. Our results revealed significant differences in geochemical parameters across the sediment biofilm/water interface in the presence and absence of U(VI) under oxic and anoxic conditions. While the pH was relatively constant within the sediment biofilm, the redox potential and the DO and H(2) concentrations were heterogeneous at the microscale (<500-1000 MUm). We found microenvironments with high DO levels (DO hotspots) when the sediment biofilm was exposed to U(VI). On the other hand, we found hotspots (high concentrations) of H(2) under anoxic conditions both in the presence and in the absence of U(VI). The presence of anoxic microenvironments inside the sediment biofilms suggests that U(VI) reduction proceeds under bulk oxic conditions. To test this, we operated our biofilm reactor under air-saturated conditions in the presence of U(VI) and characterized U speciation in the sediment biofilm. U L(III)-edge X-ray absorption spectroscopy (XANES and EXAFS) showed that 80-85% of the U was in the U(IV) valence state. PMID- 22078230 TI - Constitutive expression of a grapevine polygalacturonase-inhibiting protein affects gene expression and cell wall properties in uninfected tobacco. AB - BACKGROUND: Polygalacturonase-inhibiting proteins (PGIPs) directly limit the effective ingress of fungal pathogens by inhibiting cell wall-degrading endopolygalacturonases (ePGs). Transgenic tobacco plants over-expressing grapevine (Vitis vinifera) Vvpgip1 have previously been shown to be resistant to Botrytis infection. In this study we characterized two of these PGIP over expressing lines with known resistance phenotypes by gene expression and hormone profiling in the absence of pathogen infection. RESULTS: Global gene expression was performed by a cross-species microarray approach using a potato cDNA microarray. The degree of potential cross-hybridization between probes was modeled by a novel computational workflow designed in-house. Probe annotations were updated by predicting probe-to-transcript hybridizations and combining information derived from other plant species. Comparing uninfected Vvpgip1 overexpressing lines to wild-type (WT), 318 probes showed significant change in expression. Functional groups of genes involved in metabolism and associated to the cell wall were identified and consequent cell wall analysis revealed increased lignin-levels in the transgenic lines, but no major differences in cell wall-derived polysaccharides. GO enrichment analysis also identified genes responsive to auxin, which was supported by elevated indole-acetic acid (IAA) levels in the transgenic lines. Finally, a down-regulation of xyloglucan endotransglycosylase/hydrolases (XTHs), which are important in cell wall remodeling, was linked to a decrease in total XTH activity. CONCLUSIONS: This evaluation of PGIP over-expressing plants performed under pathogen-free conditions to exclude the classical PGIP-ePG inhibition interaction indicates additional roles for PGIPs beyond the inhibition of ePGs. PMID- 22078231 TI - Preparation and full characterization of a micro-immunoaffinity monolithic column and its in-line coupling with capillary zone electrophoresis with Ochratoxin A as model solute. AB - A micro-immunoaffinity monolithic column (MUIAC) was developed and in-line coupled with capillary zone electrophoresis in a fully automated way with Ochratoxin A as test solute. The in-line micro-immunoaffinity columns based on monolithic methacrylate polymers (EDMA-GMA) were prepared in situ at the inlet end of a PTFE coated fused silica capillary by UV initiated polymerization and subsequently grafted with antibodies. These MUIACs were thoroughly characterized. The synthesis of the polymeric support was first demonstrated to be reproducible in terms of permeability, surface properties and efficiency. The antibodies immobilization was then studied by a new original hydrodynamic method (ADECA) allowing the in situ quantitative determination (at a miniaturized scale) of the total amount of immobilized antibodies. The combination of this measurement with the binding capacity of the MUIAC allowed, for the first time, the in situ determination of immobilized antibody activity. A total of 260 +/- 15 ng (1.6 +/- 0.1 pmol) of IgG antibodies/cm in 75 MUm i.d. monolithic column (i.e. 18 MUgmg( 1)) was obtained with (anti-Ochratoxin A/Ochratoxin A) as antibody/antigen model. 40% of the immobilized antibodies remain active corresponding to a binding capacity of 1.2 +/- 0.2 pmol antigen/cm (i.e. 600 pg/cm of our test solute OTA), a very high capacity when dealing with trace analysis and with regard to the detection limits (30 pg and 0.5 pg with UV and LIF detection, respectively). The recovery yields were quantitative with negligible non-specific adsorption and allow analysis of diluted samples (1 ngmL(-1)) for a percolated volume of 10 MUL. It was also demonstrated that despite the progressive denaturation of antibodies consecutive to the elution step, the binding capacity of the MUIAC remained high enough to implement at least 15 consecutive analyses with the same column and in a fully automated way. PMID- 22078232 TI - A sub-two minutes method for monoclonal antibody-aggregate quantification using parallel interlaced size exclusion high performance liquid chromatography. AB - In process development and during commercial production of monoclonal antibodies (mAb) the monitoring of aggregate levels is obligatory. The standard assay for mAb aggregate quantification is based on size exclusion chromatography (SEC) performed on a HPLC system. Advantages hereof are high precision and simplicity, however, standard SEC methodology is very time consuming. With an average throughput of usually two samples per hour, it neither fits to high throughput process development (HTPD), nor is it applicable for purification process monitoring. We present a comparison of three different SEC columns for mAb aggregate quantification addressing throughput, resolution, and reproducibility. A short column (150 mm) with sub-two micron particles was shown to generate high resolution (~1.5) and precision (coefficient of variation (cv)<1) with an assay time below 6 min. This column type was then used to combine interlaced sample injections with parallelization of two columns aiming for an absolute minimal assay time. By doing so, both lag times before and after the peaks of interest were successfully eliminated resulting in an assay time below 2 min. It was demonstrated that determined aggregate levels and precision of the throughput optimized SEC assay were equal to those of a single injection based assay. Hence, the presented methodology of parallel interlaced SEC (PI-SEC) represents a valuable tool addressing HTPD and process monitoring. PMID- 22078233 TI - Synthesis and application of a macroporous boronate affinity monolithic column using a metal-organic gel as a porogenic template for the specific capture of glycoproteins. AB - A macroporous boronate affinity monolithic column was prepared and applied to specifically capture glycoproteins using metal-organic gels (MOGs) as a porogenic template. This newly explored application of MOGs has proven to be a more convenient method for the formation of macropores in contrast to traditional porogenic methods. The poly (3-acrylamidophenylboronic acid-co-ethylene dimethacrylate) monolithic columns were synthesized in stainless columns by in situ polymerization. To fabricate the macroporous formation with a uniformed open channel network, the preparation conditions, such as reaction temperature, the concentration of the MOGs and the ratio of monomers were systematically investigated. The prepared macroporous monoliths were characterized by scanning electron microscope (SEM) and mercury intrusion porosimetry. Furthermore, horseradish peroxidase (HRP) and transferrin (TF) were chosen as test glycoproteins, and the chromatographic analysis demonstrated that the macroporous boronate affinity monoliths exhibited a higher selectivity and better dynamic binding capacity toward glycoproteins compared with non-glycoproteins. The resulted affinity monolithic column was successfully employed to specifically capture TF from a bovine serum sample. PMID- 22078234 TI - Ionic liquids as silica deactivating agents in gas chromatography for direct analysis of primary amines in water. AB - Analysis of primary amines in aqueous samples remains a challenging analytical issue. The preferred approach by gas chromatography is hampered by interactions of free silanol groups with the highly reactive amine groups, resulting in inconsistent measurements. Here, we report a method for direct analysis of aliphatic amines and diamines in aqueous samples by gas chromatography (GC) with silanol deactivation using ionic liquids (ILs). ILs including trihexyl(tetradecyl)phosphonium bis 2,4,4-(trimethylpentyl)phosphinate (Cyphos IL 104), 1-methyl-3-propylimidazolium bis(trifluoromethylsulfonyl)imide [pmim][Tf(2)N] and N"-ethyl-N,N,N',N'-tetramethylguanidinium tris(pentafluoroethyl)trifluorophosphate [etmg][FAP] were tested as deactivating media for the GC liner. Solutions of these ILs in methanol were injected in the system prior to the analysis of primary amines. Butane-1,4-diamine (putrescine, BDA) was used as a reference amine. The best results were obtained using the imidazolium IL [pmim][Tf(2)N]. With this deactivator, excellent reproducibility of the analysis was achieved, and the detection limit of BDA was as low as 1mM. The applicability of the method was proven for the analysis of two different primary amines (C4-C5) and pentane-1,5-diamine. PMID- 22078235 TI - Determination of phenylureas herbicides in food stuffs based on matrix solid phase dispersion extraction and capillary electrophoresis with electrochemiluminescence detection. AB - A new method based on matrix solid phase dispersion-capillary electrophoresis with electrochemiluminescence detection (MSPD-CE-ECL) has been developed for the simultaneous determination of three kinds of phenylurea herbicides (PHUs). Poly beta-cyclodextrin (poly-beta-CD) was used as an additive in the running buffer to improve the separation of three analytes. The conditions for CE separation, ECL detection and effect of poly-beta-CD were investigated in detail. Under the optimal conditions, three kinds of herbicides (isoproturon, linuron and diuron) were well separated and detected within 8 min. The linear ranges of the standard solution for isoproturon and linuron were 1-300 MUg L(-1) with a detection limit (S/N=3) of 0.1 MUg L(-1), and for diuron was 2-500 MUg L(-1) with a detection limit of 0.2 MUg L(-1). The average recoveries were in the range of 86.9-102.8%, and all relative standard deviation of the migration time and the ECL intensity in intraday and interday were less than 9.0%. The proposed method was also applied to the determination of three kinds of herbicides in green vegetable and rice samples with recoveries in the range from 78.1 to 93.8%. PMID- 22078236 TI - A multi-fiber handling device for in vivo solid phase microextraction-liquid chromatography-mass spectrometry applications. AB - Solid phase microextraction, an in vivo and ex vivo sample preparation method, continues to capture growing interest among researchers for bioanalytical applications. When coupled with liquid chromatography mass spectrometry, the procedure often involves large numbers of fibers in, for example, both pharmacokinetic and pharmadynamic studies as well as other bioapplications. In this regard, appropriate and adequate precaution will be critical in preventing the fibers firstly from any possible external contamination and damage to maintain high analytical data integrity. In addition, improving the offline desorption of fibers specifically for in vivo SPME will not only help in improving data quality, but will also significantly decrease the overall analysis time. This article introduces a prototype multi-fiber handling device capable of simultaneous extraction/desorption of multiple solid phase microextraction (SPME) fibers on a 96-deep well plate format. This device thus provides an alternative approach to improving higher sample throughput for in vivo SPME liquid chromatography mass spectrometry applications. The portable design of the device ensures effective protection and prevention of fibers against damage and possible contamination and thus maintains analytical data reliability. To ensure its suitability for parallel extraction/desorption, the device was carefully evaluated using four benzodiazepines (diazepam, nordiazepam, oxazepam and lorazepam) as model drugs by monitoring inter- and intra-well variability. The effect of agitation speed on data precision and accuracy, effect of device weight on data precision, and comparison of the overall performance of the device with traditional manual desorption approach were also assessed. Results obtained from evaluation of the device with particular focus on the desorption process indicated that the weight of the device has no effect on the reliability and reproducibility of data acquired using the device. The average amount of diazepam obtained for 20 selected wells with and without device was 48.8pg and 49.4pg, respectively. Intra-, inter-well, and inter fiber variations recorded were all <=13% indicating an excellent precision and reproducibility can be attained with the device. PMID- 22078237 TI - Opposite effects of interferon-beta on new B and T cell release from production sites in multiple sclerosis patients. AB - The release of newly produced B and T lymphocytes from the production sites was analyzed in 30 multiple sclerosis patients treated with interferon-beta by measuring T-cell receptor excision circles and k-deleting recombination excision circles. We found that the therapy induces opposite effects on B- and T-cell mobilization in 33% of patients. New B-cell production, which peaks after 6 months of therapy and then decreases to levels that, however, are still higher than in controls, may cause a renewal of the B-cell compartment. On the contrary, the decreased number of newly produced T lymphocytes observed at 12 months of treatment and the association between reduced thymic output and low peripheral T lymphocytes can be a cause of leukopenia, a frequent side effect of the therapy. PMID- 22078238 TI - Galanin and alpha-MSH autoantibodies in cerebrospinal fluid of patients with Alzheimer's disease. AB - BACKGROUND: Neuropeptides galanin and alpha-melanocyte-stimulating hormone (alpha MSH) are involved in the regulation of memory and appetite. Increased galanin and decreased alpha-MSH levels were reported in postmortem brains of patients with Alzheimer's disease (AD) but the underlying mechanisms are uncertain. Here we studied if autoantibodies (autoAbs) reacting with galanin and alpha-MSH are altered in AD. METHODS: Levels of free and total IgG autoAbs reacting with galanin and alpha-MSH were measured in sera and cerebrospinal fluid (CSF) of 18 subjects with AD and in 15 age-matched non-demented controls. Values were correlated with Mini-Mental State Examination (MMSE) score, body mass index (BMI) and CSF levels of AD biomarkers. RESULTS: CSF levels of total but not free IgG autoAbs against galanin were increased in AD, resulting in increased percentage of galanin autoAbs present as immune complexes. CSF levels of galanin total autoAbs and alpha-MSH free autoAbs correlated negatively with the severity of cognitive impairment as measured by MMSE. Both total and free autoAbs against galanin and alpha-MSH in CSF correlated negatively with age in AD patients but not in controls. CSF levels of galanin autoAbs and free alpha-MSH AutoAbs negatively correlated with CSF levels of t-Tau, p-Tau and ratios of t-Tau/Abeta42 or p-Tau/Abeta42 in AD patients but not in controls. CONCLUSIONS: AutoAbs reacting with galanin and alpha-MSH are present in CSF and are associated with clinical characteristics of AD patients. The functional significance and therapeutic potential of these autoAbs should be further clarified. PMID- 22078239 TI - SvO2 to monitor resuscitation of septic patients: let's just understand the basic physiology. AB - Real-time monitoring of mixed venous oxygen blood saturation (SvO2) or of central venous oxygen blood saturation is often used during resuscitation of septic shock. However, the meaning of these parameters is far from straightforward. In the present commentary, we emphasize that SvO2--a global marker of tissue oxygen balance--can never be simplistically used as a marker of preload responsiveness, which is an intrinsic marker of cardiac performance. In some septic shock patients, because of profound hypovolemia or myocardial dysfunction, SvO2 can be low but obviously cannot alone indicate whether a fluid challenge would increase cardiac output. In other patients, because of a profound impairment of oxygen extraction capacities, SvO2 can be abnormally high even in patients who are still able to respond positively to fluid infusion. In any case, other reliable dynamic parameters can help to address the important question of fluid responsiveness/unresponsiveness. However, whether fluid administration in fluid responders and high SvO2 would be efficacious to reduce tissue dysoxia in the most injured tissues is still uncertain. PMID- 22078240 TI - Fruit and vegetables intake among elderly Iranians: a theory-based interventional study using the five-a-day program. AB - BACKGROUND: The benefit of FV intake in old age is well documented. However, there is evidence that old people do not consume enough FV. The purpose of this study was to evaluate the effectiveness of a tailored nutrition intervention that aimed to increase the FV intake among elderly Iranians aged 60 and over. METHODS: This quasi-experimental study was performed among a community-based sample of elderly in Tehran, Iran in year 2008 to 2009. Data were collected at baseline and 4 weeks follow-up. At baseline face-to-face interviews were conducted using a structured questionnaire including items on demographic information, stages of change, self-efficacy, decisional balance, daily servings of FV intake. Follow-up data were collected after implementing the intervention. RESULTS: In all 400 elderly were entered into the study (200 individuals in intervention group and 200 in control group). The mean age of participants was 64.06 +/- 4.48 years and overall two-third of participants were female. At baseline total FV intake was not differed between two groups but it was significantly increased in the intervention group at posttest assessment (mean serving/day in intervention group 3.08 +/- 1.35 vs. 1.79 +/- 1.08 in control group; P = 0.001). Further analysis also indicated that elderly in intervention group had higher FV intake, perceived benefits and self-efficacy, and lower perceived barriers. Compared with control group, greater proportions of elderly in intervention group moved from pre contemplation to contemplation/preparation and action/maintenance stages (P < 0.0001), and from contemplation/preparation to action/maintenance stages (P = 0.004) from pretest to posttest assessments. CONCLUSION: This study suggests that the Transtheoretical Model is a useful model that can be applied to dietary behavior change, more specifically FV consumption among elderly population in Iran and perhaps elsewhere with similar conditions. PMID- 22078242 TI - The importance of worry across diagnostic presentations: prevalence, severity and associated symptoms in a partial hospital setting. AB - Although excessive worry has been linked primarily with Generalized Anxiety Disorder (GAD), recent work suggests worry is dimensional, with potential relevance to a range of psychiatric disorders. The current study examined associations between worry and psychological symptoms across several primary diagnoses and tested worry's hypothesized unique relation to GAD in an acute psychiatric setting. Participants were 568 patients with primary diagnoses of Major Depression, Bipolar Disorder-Depressed, Bipolar Disorder-Manic, and Psychosis. Participants completed a structured diagnostic interview and questionnaires at admission. Partial correlations controlling for GAD diagnosis indicated that worry correlated with higher depression and poorer overall well being in the Depressed, Bipolar-Depressed, and Psychosis groups and decreased functioning in the Depressed, Bipolar-Manic, and Psychosis groups. Depressed and Bipolar-Depressed groups endorsed the highest level of worry. A comorbid anxiety disorder was associated with higher worry across primary diagnoses, even after controlling for GAD. Of the anxiety disorders, GAD and Panic Disorder diagnoses predicted higher worry scores. Results discussed in terms of conceptual implications for worry as a transdiagnostic concept and clinical interventions. PMID- 22078241 TI - Rationale and design of a randomized controlled trial of directly observed hepatitis C treatment delivered in methadone clinics. AB - BACKGROUND: Most methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment. Physicians may be reluctant to treat HCV in IDUs because of concerns about treatment adherence, psychiatric comorbidity, or ongoing drug use. Optimal HCV management approaches for IDUs remain unknown. We are conducting a randomized controlled trial in a network of nine methadone clinics with onsite HCV care to determine whether modified directly observed therapy (mDOT), compared to treatment as usual (TAU), improves adherence and virologic outcomes among opioid users. METHODS/DESIGN: We plan to enroll 80 HCV-infected adults initiating care with pegylated interferon alfa-2a (IFN) plus ribavirin, and randomize them to mDOT (directly observed daily ribavirin plus provider-administered weekly IFN) or TAU (self-administered ribavirin plus provider-administered weekly IFN). Our outcome measures are: 1) self-reported and pill count adherence, and 2) end of treatment response (ETR) or sustained viral response (SVR). We will use mixed effects linear models to assess differences in pill count adherence between treatment arms (mDOT v. TAU), and we will assess differences between treatment arms in the proportion of subjects with ETR or SVR with chi square tests. Of the first 40 subjects enrolled: 21 have been randomized to mDOT and 19 to TAU. To date, the sample is 77% Latino, 60% HCV genotype-1, 38% active drug users, and 27% HIV infected. Our overall retention rate at 24 weeks is 92%, 93% in the mDOT arm and 92% in the TAU arm. DISCUSSION: This paper describes the design and rationale of a randomized clinical trial comparing modified directly observed HCV therapy delivered in a methadone program to on-site treatment as usual. Our trial will allow rigorous evaluation of the efficacy of directly observed HCV therapy (both pegylated interferon and ribavirin) for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs, and can also guide protocols for studies among HCV-infected drug users receiving methadone for opiate dependence. PMID- 22078243 TI - Validation of the Spence Children's Anxiety Scale's obsessive compulsive subscale in a clinical and community sample. AB - This study describes the validation of the obsessive compulsive subscale on the Spence Children's Anxiety Scale (SCAS OCD) for use as a clinical assessment tool. Data from 196 anxious children (102 males, ages 7-18) and their parent collected during a diagnostic assessment were compared to data from 420 children (206 males, ages 8-13) from the community collected by mail. The validity of the SCAS OCD parent- and child-report forms were supported by correlations with the Children's Yale-Brown Obsessive Compulsive Scale and continuous OCD symptom variables from the Anxiety Disorders Interview Schedule: Child Version. In addition, children with OCD were found to have higher scores on the SCAS OCD subscale than patients without OCD and children from the community without a reported anxiety diagnosis. The sensitivity of the SCAS OCD to treatment effects was also demonstrated in a subset of the clinical sample that received exposure and response prevention therapy. Finally, cut-scores were identified that examine the sensitivity and predictive utility of the scales. PMID- 22078244 TI - Covalent linkage of N-methyl-6-oxyquinolinium betaine to trehalose. AB - The common route to link quinolinium and pyridinium fluorophores to biomolecules via bromoacetic acid has failed in labeling the disaccharide trehalose with N methyl-6-oxyquinolinium betaine: the unexpected, extremely high instability of the N-carboxymethyl ester was overcome by direct N-alkylation of the quinoline derivative with trehalose triflate. PMID- 22078245 TI - C1-esterase inhibitor protects against early vein graft remodeling under arterial blood pressure. AB - OBJECTIVES: Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. METHODS: Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. RESULTS: Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. CONCLUSION: C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting. PMID- 22078248 TI - Experience of nursing leaders. PMID- 22078247 TI - Age- and sex-related differences in vascular function and vascular response to mental stress. Longitudinal and cross-sectional studies in a cohort of healthy children and adolescents. AB - OBJECTIVE: Limited data, especially from longitudinal studies, are available regarding vascular health assessment in childhood. In this study, we performed longitudinal and cross-sectional studies in healthy children and adolescents to investigate age- and sex-related differences in vascular functions and vascular response to mental stress. METHODS: Pulse wave velocity (PWV) was measured by tonometry. Endothelial function and vascular response to mental arithmetic test were assessed using a peripheral artery tonometry device. Data were obtained in 162 adolescents (mean age of 17 years, 94 girls) in a 3-year follow-up study and 241 children (mean age of 10 years, 115 girls) in a first-time investigation. Physical activity was assessed in adolescents by a self-report questionnaire. RESULTS: Our 3-year follow-up study revealed that the increased PWV was greater in male adolescents (0.79+/-0.79m/s) than in females (0.27+/-0.89m/s, p<0.001). Adolescents who reported decreased physical activity over the 3-year period had increased arterial stiffness. Comparing the cross-sectional data, we found that sex-related differences in reactive hyperemic response was more apparent by evaluating the overall response curve than measuring the reactive hyperemic index from one arbitrary time point, with lower peak response and smaller area-under curve found in boys. Moreover, we found that, in response to mental stress, male adolescents had a more vasoconstrictive response, followed by a less vasodilatory response, and needed longer time to return to baseline level than the females. CONCLUSION: These findings suggest that boys are likely to have adverse changes in vascular health earlier than the age-matched girls. PMID- 22078246 TI - Relationship between hemodynamics and atherosclerosis in aortic arches of apolipoprotein E-null mice on 129S6/SvEvTac and C57BL/6J genetic backgrounds. AB - OBJECTIVE: We investigated the relationships between hemodynamics and differential plaque development at the aortic arch of apolipoprotein E (apoE) null mice on 129S6/SvEvTac (129) and C57BL/6J (B6) genetic backgrounds. METHODS: Mean flow velocities at the ascending and descending aorta (mVAA and mVDA) were measured by Doppler ultrasound in wild type and apoE-null male mice at 3 and 9 months of age. Following dissection of the aortic arches, anatomical parameters and plaque areas were evaluated. RESULTS: Arch plaques were five times bigger in 129-apoE than in B6-apoE mice at 3 months, and twice as large at 9 months. The geometric differences, namely larger vessel diameter in the B6 strain and broader inner curvature of the aortic arch in the 129 strain, were exaggerated in 9-month old apoE-null mice. Cardiac output and heart rate under anesthesia were significantly higher in the B6 strain than in the 129 strain. The values of mVAA were similar in the two strains, while mVDA was lower in the 129 strain. However, there was a 129-apoE-specific reduction of flow velocities with age, and both mVAA and mVDA were significantly lower in 129-apoE than in B6-apoE mice at 9 months. The mean relative wall shear stress (rWSS) over the aortic arch in 129 apoE and B6-apoE mice were not different, but animals with lower mean rWSS had larger arch plaques within each strain. CONCLUSIONS: The plaque formation in the arch of apoE-null mice is accompanied by strain-dependent changes in both arch geometry and hemodynamics. While arch plaque sizes negatively correlate with mean rWSS, additional factors are necessary to account for the strain differences in arch plaque development. PMID- 22078249 TI - A position paper: the continuing dilemma in nursing education. PMID- 22078250 TI - Characterisation and application of a novel positively charged nanofiltration membrane for the treatment of textile industry wastewaters. AB - The present study demonstrates the high potential for the application of a novel self assembled positively charged nanofiltration membrane, PA6DT-C, in processes such as the recovery of valuable cationic macromolecules in the bioprocess and pharmaceutical industries or removal of multi-valent cations such as dyes and heavy metals in the paper and pulp, textiles, nuclear, and automotive industries. The nanofiltration membrane, prepared in this laboratory, is further characterised and then tested for the removal and recovery of Methylene Blue from a synthetic dye house wastewater. The characterisation process involved the construction of a rejection profile for NaCl over a wide range of pH and concentration, which illustrates that the optimal process conditions for the removal of small cations using this membrane is in the region pH <8.0 and concentration less than 15 mol m(-3). The salt rejection data was used to calculate the magnitude of the effective membrane charge density and this was found to be significantly higher for the PA6DT-C membrane than two commercially available membranes (Desal-DK and Nanomax-50). The membrane flux for this new membrane is also superior to the commercial membranes with an approximate increase of 3-4 fold. The PA6DT-C membrane was successful in removal of Methylene Blue dye from synthetic dye house wastewaters achieving 98% rejection and a membrane flux of ~ 17 LMH bar(-1). Thus, this new membrane both adds to and complements the existing short supply of positively charged NF membranes. PMID- 22078251 TI - Polyaluminum chloride with high Al30 content as removal agent for arsenic contaminated well water. AB - Polyaluminum chloride (PACl) is a well-established coagulant in water treatment with high removal efficiency for arsenic. A high content of Al(30) nanoclusters in PACl improves the removal efficiency over broader dosage and pH range. In this study we tested PACl with 75% Al(30) nanoclusters (PACl(Al30)) for the treatment of arsenic-contaminated well water by laboratory batch experiments and field application in the geothermal area of Chalkidiki, Greece, and in the Pannonian Basin, Romania. The treatment efficiency was studied as a function of dosage and the nanoclusters' protonation degree. Acid-base titration revealed increasing deprotonation of PACl(Al30) from pH 4.7 to the point of zero charge at pH 6.7. The most efficient removal of As(III) and As(V) coincided with optimal aggregation of the Al nanoclusters at pH 7-8, a common pH range for groundwater. The application of PACl(Al30) with an Al(tot) concentration of 1-5mM in laboratory batch experiments successfully lowered dissolved As(V) concentrations from 20 to 230 MUg/L to less than 5 MUg/L. Field tests confirmed laboratory results, and showed that the WHO threshold value of 10 MUg/L was only slightly exceeded (10.8 MUg/L) at initial concentrations as high as 2300 MUg/L As(V). However, As(III) removal was less efficient (<40%), therefore oxidation will be crucial before coagulation with PACl(Al30). The presence of silica in the well water improved As(III) removal by typically 10%. This study revealed that the Al(30) nanoclusters are most efficient for the removal of As(V) from water resources at near-neutral pH. PMID- 22078252 TI - TiO2 and Fe (III) photocatalytic ozonation processes of a mixture of emergent contaminants of water. AB - A mixture of three emergent contaminants: testosterone (TST), bisphenol A (BPA) and acetaminophen (AAP) has been treated with different photocatalytic oxidation systems. Homogeneous catalysts as Fe(III) alone or complexed with oxalate or citrate ions, heterogeneous catalysts as titania, and oxidants such as hydrogen peroxide and/or ozone have been used to constitute the oxidation systems. For the radiation type, black light lamps mainly emitting at 365 nm have been used. The effects of pH (3 and 6.5) have been investigated due to the importance of this variable both in ozone and Fe(III) systems. Removal of initial compounds and mineralization (total organic carbon: TOC) were followed among other parameters. For the initial compounds removal ozonation alone, in many cases, allows the highest elimination rates, regardless of the presence or absence of UVA light and catalyst. For mineralization, however, ozone photocatalytic processes clearly leads to the highest oxidation rates. PMID- 22078253 TI - Risk prioritisation of stormwater pollutant sources. AB - This paper describes the development of a pollutant risk prioritisation methodology for the comparative assessment of stormwater pollutants discharged from differing land use types and activities. Guidelines are presented which evaluate available data with respect to 'likelihood of occurrence' and 'severity of impact'. The use of the developed approach is demonstrated through its application to total suspended solids, biochemical oxygen demand, lead and cadmium. The proposed benchmarking scheme represents a transparent and auditable mechanism to support the synthesis of data from a variety of sources and is sufficiently flexible to incorporate the use of chemical, physical and/or ecological data sets. Practitioners involved in developing and implementing pollutant mitigation programmes are assisted in two key ways. Firstly through enabling the risks to receiving waters from diffuse pollution on a source-by source and/or pollutant-by-pollutant basis at a catchment scale to be comparatively assessed and prioritised. Secondly, the methodology informs the selection of appropriate diffuse pollution control strategies. PMID- 22078254 TI - Efficient electricity generation from sewage sludge using biocathode microbial fuel cell. AB - Microbial fuel cells (MFCs) with abiotic cathodes require expensive catalyst (such as Pt) or catholyte (such as hexacynoferrate) to facilitate oxidation reactions. This study incorporated biocathodes into a three-chamber MFC to yield electricity from sewage sludge at maximum power output of 13.2 +/- 1.7 W/m(3) during polarization, much higher than those previously reported. After 15 d operation, the total chemical oxygen demand (TCOD) removal and coulombic efficiency (CE) of cell reached 40.8 +/- 9.0% and 19.4 +/- 4.3%, respectively. The anolyte comprised principally acetate and propionate (minor) as metabolites. The use of biocathodes produced an internal resistance of 36-46 Omega, lower than those reported in literature works, hence yielding higher maximum power density from MFC. The massively parallel sequencing technology, 454 pyrosequencing technique, was adopted to probe microbial community on anode biofilm, with dominant phyla belonging to Proteobacteria (45% of total bacteria), Bacteroidetes (19%), Uncultured bacteria (9%), Actinobacteria (7%), Firmicutes (7%), Chloroflex (7%). At genera level, Rhodoferax, Ferruginibacter, Propionibacterium, Rhodopseudomonas, Ferribacterium, Clostridium, Chlorobaculum, Rhodobacter, Bradyrhizobium were the abundant taxa (relative abundances>2.0%). PMID- 22078255 TI - Influence of temperature and salinity on Ostreopsis cf. ovata growth and evaluation of toxin content through HR LC-MS and biological assays. AB - In the Mediterranean Sea, blooms of Ostreopsis cf. ovata and Ostreopsis siamensis have become increasingly frequent in the last decade and O. cf. ovata was found to produce palytoxin-like compounds (putative palytoxin, ovatoxin-a, -b, -c, -d and -e), a class of highly potent toxins. The environmental conditions seem to play a key role in influencing the abundance of Ostreopsis spp. High cell densities are generally recorded in concomitance with relatively high temperature and salinity and low hydrodynamics conditions. In this study the effects of temperature and salinity on the growth and toxicity of an Adriatic O. cf. ovata isolate were investigated. The highest growth rates of the Adriatic strain were recorded for cultures grown at 20 degrees C and at salinity values of 36 and 40, in accordance with natural bloom surveys. Toxicity was affected by growth conditions, with the highest toxin content on a per cell basis being measured at 25 degrees C and salinity 32. However, the highest total toxin content on a per litre basis was recorded at 20 degrees C and salinity 36, since under such conditions the growth yield was the highest. O. cf. ovata had lethal effects on Artemia nauplii and juvenile sea basses, and produced haemolysis of sheep erythrocytes. A comparison between haemolysis neutralization assay and HR LC-MS results showed a good correlation between haemolytic effect and total toxin content measured through HR LC-MS. Considering the increasing need for rapid and sensitive methods to detect palytoxin in natural samples, the haemolytic assay appears a useful method for preliminary quantification of the whole of palytoxin like compounds in algal extracts. PMID- 22078256 TI - Effects of microcystin-LR on the metal bioaccumulation and toxicity in Chlamydomonas reinhardtii. AB - Microcystin-LR (MC-LR) is one of the most notorious toxins liberated from cyanobacteria in eutrophicated freshwater ecosystems. Its effects on the bioaccumulation and toxicity of Cd(2+), CrO(4)(2-), Cu(2+), and Zn(2+) in a green alga Chlamydomonas reinhardtii were investigated in the present study. The metal bioaccumulation in the alga was unaffected by MC-LR. The surface-adsorbed and intracellular metal concentrations in the treatments with and without the addition of MC-LR could be well simulated by a single Freundlich isotherm for each metal with their accumulation ability following the order of Cu(2+) > Cd(2+) > Zn(2+) > CrO(4)(2-). The bioavailable metal concentrations measured by diffusion gradients in thin-films remained unchanged when MC-LR was applied. Accordingly, the growth of C. reinhardtii was similarly inhibited at the same metal concentration regardless of the addition of MC-LR. The metal toxicity could also be well delineated with the classic free ion activity and biotic ligand models. However, the intracellular metal concentration was found to have the best predictability suggesting its more direct relationship with metal toxicity. Metal exposure induced the accumulation of MC-LR in the alga, which was leveled off at high metal levels. The underlying uptake mechanisms need to be further examined. PMID- 22078257 TI - The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) is associated with schizophrenia and modulates verbal memory and the acoustic startle response. AB - Recently, the neuropeptide S (NPS) neurotransmitter system has been identified as a promising psychopharmacological drug target given that NPS has shown anxiolytic like and stress-reducing properties and memory-enhancing effects in rodent models. NPS binds to the G-protein-coupled receptor encoded by the neuropeptide S receptor gene (NPSR1). A functional variant within this gene leads to an amino acid exchange (rs324981, Asn107Ile) resulting in a gain-of-function in the Ile107 variant which was recently associated with panic disorder in two independent studies. A potential psychopharmacological effect of NPS on schizophrenia psychopathology was demonstrated by showing that NPS can block NMDA antagonist induced deficits in prepulse inhibition. We therefore explored a potential role of the NPSR1 Asn107Ile variation in schizophrenia. A case-control sample of 778 schizophrenia patients and 713 healthy control subjects was successfully genotyped for NPSR1 Asn107Ile. Verbal declarative memory and acoustic startle response were measured in subsamples of the schizophrenia patients. The case control comparison revealed that the low-functioning NPSR1 Asn107 variant was significantly associated with schizophrenia (OR 1.19, p=0.017). Moreover, specifically decreased verbal memory consolidation was found in homozygous Asn107 carriers while memory acquisition was unaffected by NPSR1 genotype. The schizophrenia patients carrying the Ile107 variant demonstrated significantly reduced startle amplitudes but unaffected prepulse inhibition and habituation. The present study confirms findings from rodent models demonstrating an effect of NPS on memory consolidation and startle response in schizophrenia patients. Based on these findings, we consider NPS as a promising target for antipsychotic drug development. PMID- 22078258 TI - INbreast: toward a full-field digital mammographic database. AB - RATIONALE AND OBJECTIVES: Computer-aided detection and diagnosis (CAD) systems have been developed in the past two decades to assist radiologists in the detection and diagnosis of lesions seen on breast imaging exams, thus providing a second opinion. Mammographic databases play an important role in the development of algorithms aiming at the detection and diagnosis of mammary lesions. However, available databases often do not take into consideration all the requirements needed for research and study purposes. This article aims to present and detail a new mammographic database. MATERIALS AND METHODS: Images were acquired at a breast center located in a university hospital (Centro Hospitalar de S. Joao [CHSJ], Breast Centre, Porto) with the permission of the Portuguese National Committee of Data Protection and Hospital's Ethics Committee. MammoNovation Siemens full-field digital mammography, with a solid-state detector of amorphous selenium was used. RESULTS: The new database-INbreast-has a total of 115 cases (410 images) from which 90 cases are from women with both breasts affected (four images per case) and 25 cases are from mastectomy patients (two images per case). Several types of lesions (masses, calcifications, asymmetries, and distortions) were included. Accurate contours made by specialists are also provided in XML format. CONCLUSION: The strengths of the actually presented database-INbreast relies on the fact that it was built with full-field digital mammograms (in opposition to digitized mammograms), it presents a wide variability of cases, and is made publicly available together with precise annotations. We believe that this database can be a reference for future works centered or related to breast cancer imaging. PMID- 22078259 TI - The cerebellum in dystonia - help or hindrance? AB - Dystonia has historically been considered a disorder of the basal ganglia. This review aims to critically examine the evidence for a role of the cerebellum in the pathophysiology of dystonia. We compare and attempt to link the information available from both clinical and experimental studies; work detailing cerebellar connectivity in primates; data that suggests a role for the cerebellum in the genesis of dystonia in murine models; clinical observation in humans with structural lesions and heredodegenerative disorders of the cerebellum; and imaging studies of patients with dystonia. The typical electrophysiological findings in dystonia are the converse to those found in cerebellar lesions. However, certain subtypes of dystonia mirror cerebellar patterns of increased cortical inhibition. Furthermore, altered cerebellar function can be demonstrated in adult onset focal dystonia with impaired cerebellar inhibition of motor cortex and abnormal eyeblink classical conditioning. We propose that abnormal, likely compensatory activity of the cerebellum is an important factor within pathophysiological models of dystonia. Work in this exciting area has only just begun but it is likely that the cerebellum will have a key place within future models of dystonia. PMID- 22078260 TI - Reversibility of cadmium sorption to calcite revisited. AB - Cadmium sorption to calcite was studied in aqueous solution at calco-carbonic (CO(2)-H(2)O-CaCO(3)) equilibrium and at concentrations below the solubility product of otavite (<10(-7) mol L(-1)). Experiments were conducted in a stirred flow-through reactor, lasting for 15 and 60 h at flow rates of 1.6 and 0.5 mL min(-1), respectively. Under both flow conditions, the cadmium breakthrough curves reached steady state after a flow time of about 50 reactor volumes, but different calcite saturation levels were achieved, which implied time-dependent sorption rates. Desorption of cadmium was induced by switching from Cd-containing to Cd-free solution in the reactor inflow. Reversibility of sorption was then evaluated by comparing amounts sorbed and desorbed over identical time intervals. On average, the desorption/sorption ratio was 95+/-10%. Desorption rates were close to those for sorption and showed the same time dependency: Initially, rates were fast and slowed down with time. "Irreversible" surface reactions such as solid-solution formation could not be inferred. In previous research, cadmium sorption was often shown to be partly irreversible. We surmise that calcite surface ripening is conditioned by the concentration of lattice-building ions in the EDL. At calco-carbonic equilibrium, these ion concentrations at the surface are lowest. Therefore, irreversible binding of cadmium is not favoured. PMID- 22078261 TI - Reduced inflammation accompanies diminished myelin damage and repair in the NG2 null mouse spinal cord. AB - BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease in which blood derived immune cells and activated microglia damage myelin in the central nervous system. While oligodendrocyte progenitor cells (OPCs) are essential for generating oligodendrocytes for myelin repair, other cell types also participate in the damage and repair processes. The NG2 proteoglycan is expressed by OPCs, pericytes, and macrophages/microglia. In this report we investigate the effects of NG2 on these cell types during spinal cord demyelination/remyelination. METHODS: Demyelinated lesions were created by microinjecting 1% lysolecithin into the lumbar spinal cord. Following demyelination, NG2 expression patterns in wild type mice were studied via immunostaining. Immunolabeling was also used in wild type and NG2 null mice to compare the extent of myelin damage, the kinetics of myelin repair, and the respective responses of OPCs, pericytes, and macrophages/microglia. Cell proliferation was quantified by studies of BrdU incorporation, and cytokine expression levels were evaluated using qRT-PCR. RESULTS: The initial volume of spinal cord demyelination in wild type mice is twice as large as in NG2 null mice. However, over the ensuing 5 weeks there is a 6-fold improvement in myelination in wild type mice, versus only a 2-fold improvement in NG2 null mice. NG2 ablation also results in reduced numbers of each of the three affected cell types. BrdU incorporation studies reveal that reduced cell proliferation is an important factor underlying NG2-dependent decreases in each of the three key cell populations. In addition, NG2 ablation reduces macrophage/microglial cell migration and shifts cytokine expression from a pro-inflammatory to anti-inflammatory phenotype. CONCLUSIONS: Loss of NG2 expression leads to decreased proliferation of OPCs, pericytes, and macrophages/microglia, reducing the abundance of all three cell types in demyelinated spinal cord lesions. As a result of these NG2-dependent changes, the course of demyelination and remyelination in NG2 null mice differs from that seen in wild type mice, with both myelin damage and repair being reduced in the NG2 null mouse. These studies identify NG2 as an important factor in regulating myelin processing, suggesting that therapeutic targeting of the proteoglycan might offer a means of manipulating cell behavior in demyelinating diseases. PMID- 22078263 TI - Constraints to universal coverage: inequities in health service use and expenditures for different health conditions and providers. AB - BACKGROUND: There is need for new information about the socio-economic and geographic differences in health seeking and expenditures on many health conditions, so to help to design interventions that will reduce inequity in utilisation of healthcare services and ensure universal coverage. OBJECTIVES: The paper contributes additional knowledge about health seeking and economic burden of different health conditions. It also shows the level of healthcare payments in public and private sector and their distribution across socioeconomic and geographic population groups. METHODS: A questionnaire was used to collect data from randomly selected householders from 4,873 households (2,483 urban and 2,390 rural) in southeast Nigeria. Data was collected on: health problems that people had and sought care for; type of care sought, outpatient department (OPD) visits and inpatient department (IPD) stays; providers visited; expenditures; and preferences for improving access to care. Data was disaggregated by socio economic status (SES) and geographic location (urban versus rural) of the households. RESULTS: Malaria and hypertension were the major communicable and non communicable diseases respectively that required OPD and IPD. Patent medicine dealers (PMDs) were the most commonly used providers (41.1%), followed by private hospitals (19.7%) and pharmacies (16.4%). The rural dwellers and poorer SES groups mostly used low-level and informal providers. The average monthly treatment expenditure in urban area was 2444 Naira (US$20.4) and 2267 Naira (US$18.9) in the rural area. Higher SES groups and urbanites incurred higher health expenditures. People that needed healthcare services did not seek care mostly because the health condition was not serious enough or they could not afford the cost of services. CONCLUSION: There were inequities in use of the different providers, and also in expenditures on treatment. Reforms should aim to decrease barriers to access to public and formal health services and also identify constraints which impede the equitable distribution and access of public health services for the general population especially for poor people and rural dwellers. PMID- 22078262 TI - SCFIA: a statistical corresponding feature identification algorithm for LC/MS. AB - BACKGROUND: Identifying corresponding features (LC peaks registered by identical peptides) in multiple Liquid Chromatography/Mass Spectrometry (LC-MS) datasets plays a crucial role in the analysis of complex peptide or protein mixtures. Warping functions are commonly used to correct the mean of elution time shifts among LC-MS datasets, which cannot resolve the ambiguity of corresponding feature identification since elution time shifts are random. We propose a Statistical Corresponding Feature Identification Algorithm(SCFIA) based on both elution time shifts and peak shape correlations between corresponding features. SCFIA first trains a set of statistical models, and then, all candidate corresponding features are scored by the statistical models to find the maximum likelihood solution. RESULTS: We test SCFIA on publicly available datasets. We first compare its performance with that of warping function based methods, and the results show significant improvements. The performance of SCFIA on replicates datasets and fractionated datasets is also evaluated. In both cases, the accuracy is above 90%, which is near optimal. Finally the coverage of SCFIA is evaluated, and it is shown that SCFIA can find corresponding features in multiple datasets for over 90% peptides identified by Tandem MS. CONCLUSIONS: SCFIA can be used for accurate corresponding feature identification in LC-MS. We have shown that peak shape correlation can be used effectively for improving the accuracy. SCFIA provides high coverage in corresponding feature identification in multiple datasets, which serves the basis for integrating multiple LC-MS measurements for accurate peptide quantification. PMID- 22078264 TI - Differential function of NBS1 and ATR in neurogenesis. AB - MRN (MRE11/RAD50/NBS) helps to activate ATM in response to DNA double strand breaks (DSBs) and also facilitates ATR activation by catalyzing the formation and extension of DNA single strand breaks (SSBs). Mutations of NBS1 and ATR cause human genomic instability syndrome NBS and ATR-Seckel, respectively, both of which feature neurodevelopmental defects. Whether these two DNA damage response components interact to prevent neuropathology is largely unknown. Here we show that a deletion of Nbs1 or Atr in the mouse central nervous system (CNS) results in neurodevelopmental defects characterized by reduced proliferation and increased apoptosis in embryonic brains. In contrast to Nbs1, deletion of Atr alone and both Nbs1 and Atr in the CNS causes early postnatal lethality, indicating a wider function of Atr. Importantly, deletion of Nbs1 and Atr together results in dramatic proliferation defects in neuroprogenitors. Whereas most apoptosis in the Nbs1-deleted cortex is restricted to the highly proliferating progenitors, Atr knockout induces apoptosis in both proliferating and non-proliferating neural cells. Consistently, an inducible deletion of Atr or Nbs1-Atr, but not of Nbs1, triggers a p53-independent cell death pathway in differentiated neurons, albeit elevated DNA damage in Nbs1 null neurons. Altogether, we identify a distinct function of Nbs1 and Atr in neurogenesis, namely a specific function of Nbs1 in proliferating neuroprogenitors and of Atr in both proliferating and non-dividing cells. PMID- 22078265 TI - Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer. AB - BACKGROUND: Adiponectin is inversely related to BMI, positively correlates with insulin sensitivity, and has anti-atherogenic effects. In recent years, adiponectin has been well studied in the field of oncology. Adiponectin has been shown to have antiproliferative effects on gastric cancer, and adiponectin expression is inversely correlated with clinical staging of the disease. However, no studies have reported the correlation between serum adiponectin and receptor expression with disease progression. METHODS: In this study, we evaluated expression levels of 2 adiponectin receptors--AdipoR1 and AdipoR2--and attempted to correlate their expression with prognosis in gastric cancer patients. AdipoR1 and AdipoR2 expression in gastric cancer cell lines (MKN45, TMK-1, NUGC3, and NUGC4) was evaluated by western blotting analysis, and the antiproliferative potential of adiponectin was examined in vitro. Serum adiponectin levels were evaluated in 100 gastric cancer patients, and the expression of AdipoR1 and AdipoR2 was assessed by immunohistochemical staining. RESULTS: MKN45 and NUGC3 expressed higher levels of AdipoR1 compared to NUGC4, even though there was no significance in AdipoR2 expression. The antiproliferative effect of adiponectin was confirmed in MKN45 and NUGC3 at 10 MUg/ml. No significant associations were observed between serum adiponectin levels and clinicopathological characteristics, but lymphatic metastasis and peritoneal dissemination were significantly higher in the negative AdipoR1 immunostaining group (24/32, p = 0.013 and 9/32, p = 0.042, respectively) compared to the positive AdipoR1 group (lymphatic metastasis, 33/68; peritoneal dissemination, 8/68). On the other hand, AdipoR2 expression was only associated with histopathological type (p = 0.001). In survival analysis, the AdipoR1 positive staining group had significantly longer survival rates than the negative staining group (p = 0.01). However, multivariate analysis indicated that AdipoR1 was not an independent prognostic factor on patient's survival on gastric cancer. CONCLUSIONS: In gastric cancer, adiponectin has the possibility to be involved in cell growth suppression via AdipoR1. The presence of AdipoR1 could be a novel anticancer therapeutic target in gastric cancer. PMID- 22078266 TI - FIBTEM provides early prediction of massive transfusion in trauma. AB - INTRODUCTION: Prediction of massive transfusion (MT) among trauma patients is difficult in the early phase of trauma management. Whole-blood thromboelastometry (ROTEM(r)) tests provide immediate information about the coagulation status of acute bleeding trauma patients. We investigated their value for early prediction of MT. METHODS: This retrospective study included patients admitted to the AUVA Trauma Centre, Salzburg, Austria, with an injury severity score >=16, from whom blood samples were taken immediately upon admission to the emergency room (ER). ROTEM(r) analyses (extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor and the platelet inhibitor cytochalasin D (FIBTEM) tests) were performed. We divided patients into two groups: massive transfusion (MT, those who received >=10 units red blood cell concentrate within 24 hours of admission) and non-MT (those who received 0 to 9 units). RESULTS: Of 323 patients included in this study (78.9% male; median age 44 years), 78 were included in the MT group and 245 in the non-MT group. The median injury severity score upon admission to the ER was significantly higher in the MT group than in the non-MT group (42 vs 27, P < 0.0001). EXTEM and INTEM clotting time and clot formation time were significantly prolonged and maximum clot firmness (MCF) was significantly lower in the MT group versus the non-MT group (P < 0.0001 for all comparisons). Of patients admitted with FIBTEM MCF 0 to 3 mm, 85% received MT. The best predictive values for MT were provided by hemoglobin and Quick value (area under receiver operating curve: 0.87 for both parameters). Similarly high predictive values were observed for FIBTEM MCF (0.84) and FIBTEM A10 (clot amplitude at 10 minutes; 0.83). CONCLUSIONS: FIBTEM A10 and FIBTEM MCF provided similar predictive values for massive transfusion in trauma patients to the most predictive laboratory parameters. Prospective studies are needed to confirm these findings. PMID- 22078267 TI - Phyt'Eaux Cites: application and validation of a programme to reduce surface water contamination with urban pesticides. AB - This paper presents first results of Phyt'Eaux Cites, a program put in place by the local water supply agency, the SEDIF (Syndicat des Eaux d'Ile-de-France), in collaboration with 73 local authorities, private societies and institutional offices (365 km(2)). The challenges included: measurement of the previous surface water contamination, control of urban pesticide applications, prevention of pesticide hazard on users and finally a overall reduction of surface water contamination. An inquiry on urban total pesticide amount was coupled with a surface water bi-weekly monitoring to establish the impact of more than 200 molecules upon the Orge River. For 2007, at least 4400 kg and 92 type of pesticides (essentially herbicides) were quantified for all urban users in the Phyt'Eaux Cites perimeter. At the outlet of the Orge River (bi-weekly sampling in 2007), 11 molecules were always detected above 0.1 MUg L(-1). They displayed the mainly urban origin of pesticide surface water contamination. Amitrole, AMPA (Aminomethyl Phosphonic Acid), demethyldiuron, diuron, glyphosate and atrazine were quantified with a 100% of frequency in 2007 and 2008 at the Orge River outlet. During the year, peaks of contamination were also registered for MCCP, 2,4 MCPA, 2,4 D, triclopyr, dichlorprop, diflufenican, active substances used in large amount in the urban area. However, some other urban molecules, such as isoxaben or flazasulfuron, were detected with low frequency. During late spring and summer, contamination patterns and load were dominated by glyphosate, amitrole and diuron, essentially applied by cities and urban users. Both isoproturon and chlortoluron were quantified during autumn and winter months according to upstream agricultural practices. In conclusion, 3 years after the beginning of this programme, the cities reduced the use of 68% of the total pesticide amount. An improvement on surface water quality was found from 2008 and during 2009 for all pesticides. In particular, glyphosate showed a decrease of the load above 60% in 2008, partly related to the Phyt'Eaux Cites action. PMID- 22078268 TI - Lesser than diabetes hyperglycemia in pregnancy is related to perinatal mortality: a cohort study in Brazil. AB - BACKGROUND: Gestational diabetes related morbidity increases along the continuum of the glycemic spectrum. Perinatal mortality, as a complication of gestational diabetes, has been little investigated. In early studies, an association was found, but in more recent ones it has not been confirmed. The Brazilian Study of Gestational Diabetes, a cohort of untreated pregnant women enrolled in the early 1990's, offers a unique opportunity to investigate this question. Thus, our objective is to evaluate whether perinatal mortality increases in a continuum across the maternal glycemic spectrum. METHODS: We prospectively enrolled and followed 4401 pregnant women attending general prenatal care clinics in six Brazilian state capitals, without history of diabetes outside of pregnancy, through to birth, and their offspring through the early neonatal period. Women answered a structured questionnaire and underwent a standardized 2-hour 75-g oral glucose tolerance test (OGTT). Obstetric care was maintained according to local protocols. We obtained antenatal, delivery and neonatal data from hospital records. Odds ratios (OR) were estimated using logistic regression. RESULTS: We ascertained 97 perinatal deaths (67 fetal and 31 early neonatal). Odds of dying increased according to glucose levels, statistically significantly so only for women delivering at gestational age >=34 weeks (p < 0.05 for glycemia-gestational age interaction). ORs for a 1 standard deviation difference in glucose, when analyzed continuously, were for fasting 1.47 (95% CI 1.12, 1.92); 1-h 1.55 (95% CI 1.15, 2.07); and 2-h 1.53 (95% CI 1.15, 2.02). The adjusted OR for IADPSG criteria gestational diabetes was 2.21 (95% CI 1.15, 4.27); and for WHO criteria gestational diabetes, 3.10 (95% CI 1.39, 6.88). CONCLUSIONS: In settings of limited detection and treatment of gestational diabetes mellitus, women across a spectrum of lesser than diabetes hyperglycemia, experienced a continuous rise in perinatal death with increasing levels of glycemia after 34 weeks of pregnancy. Current GDM diagnostic criteria identified this increased risk of mortality. PMID- 22078269 TI - MUC1 mucin is expressed on human T-regulatory cells: function in both co stimulation and co-inhibition. AB - MUC1 mucin, an important protein of epithelial cells and epithelial-derived carcinomas, is also expressed on activated T cells, showing both positive and negative regulatory functions. It is currently unknown whether MUC1 is a true regulatory protein of T cells and what conditions lead to MUC1 co-stimulation versus co-inhibition. We have found that MUC1 is expressed on the majority of T regulatory cells (CD4(+)/CD25(+)/FoxP3(+)) in humans (>90%) and that CD3/MUC1 co stimulation leads to an increased number of T-regulatory cells. We also discovered that the immunoregulatory function is dependent upon the number of accessory (CD3(-)) cells present, with co-inhibition occurring with <5-10% accessory cells while co-stimulation begins with a reconstitution of ~50% accessory cells. Co-inhibition was also found to not be the result of the apoptosis but a separate and unknown pathway. This data further characterizes MUC1 as an immunoregulatory protein of T cells capable of giving a positive or negative stimulus. PMID- 22078270 TI - The role of PIM kinases in human and mouse CD4+ T cell activation and inflammatory bowel disease. AB - PIM kinases are a family of three serine/threonine kinases expressed following T cell activation. Using potent selective small molecule antagonists of PIM-1/3 kinases, we demonstrate a potential role for these enzymes in naive and effector CD4+ T cell activation. PIM-1/3 inhibition prevented CD4+ T cell proliferation by inducing a G0/G1 cell cycle arrest without affecting cellular survival. In the absence of PIM-1/3 kinase activity, naive CD4+ T cells failed to fully differentiate into effector cells both in vitro and in vivo. Therapeutic dosing of a PIM-1/3 inhibitor was efficacious in a CD4+ T cell-mediated model of inflammatory bowel disease suggesting that PIM-1 and PIM-3 kinase activity contributes to sustained disease severity. These results demonstrate that PIM-1/3 kinases have an important role in CD4+ T cell responses and inhibition of this activity may provide a therapeutic benefit in T cell-mediated diseases. PMID- 22078272 TI - Effect of walking speed on inter-joint coordination differs between young and elderly adults. AB - Investigating inter-joint coordination at different walking speeds in young and elderly adults could provide insights to age-related changes in neuromuscular control of gait. We examined effects of walking speed and age on the pattern and variability of inter-joint coordination. Gait analyses of 10 young and 10 elderly adults were performed with different self-selected speeds, including a preferred, faster, and slower speed. Continuous relative phase (CRP), derived from phase planes of two adjacent joints, was used to assess the inter-joint coordination. CRP patterns were examined with cross-correlation measures and root-mean-square (RMS) differences when comparing ensemble mean curves of the faster or slower speed to preferred speed walking. Variability of coordination for each participant was assessed with the average value of all standard deviations calculated for each data point over a gait cycle from all CRP curves, namely the deviation phase (DP). For hip-knee CRP pattern, RMS differences were significantly greater between the slower and preferred walking speeds than between the faster and preferred walking speeds in young adults, but this was not found in elderly adults. Significant group differences in RMS differences and cross-correlation measures were detected in hip-knee CRP patterns between the slower and preferred walking speeds. No significant walking speed or age effects were detected for the knee-ankle CRP. Significant walking speed effects were also detected in hip-knee DP values. However, no significant group differences were detected for all three speeds. These findings suggested that young and elder adults compromise changes of walking speed with different neuromuscular control strategies. PMID- 22078271 TI - Histamine H(1) receptor signaling regulates effector T cell responses and susceptibility to coxsackievirus B3-induced myocarditis. AB - Susceptibility to autoimmune myocarditis has been associated with histamine release by mast cells during the innate immune response to coxsackievirus B3 (CVB3) infection. To investigate the contribution of histamine H(1) receptor (H(1)R) signaling to CVB3-induced myocarditis, we assessed susceptibility to the disease in C57BL/6J (B6) H(1)R(-/-) mice. No difference was observed in mortality between CVB3-infected B6 and H(1)R(-/-) mice. However, analysis of their hearts revealed a significant increase in myocarditis in H(1)R(-/-) mice that is not attributed to increased virus replication. Enhanced myocarditis susceptibility correlated with a significant expansion in pathogenic Th1 and Vgamma4(+) gammadelta T cells in the periphery of these animals. Furthermore, an increase in regulatory T cells was observed, yet these cells were incapable of controlling myocarditis in H(1)R(-/-) mice. These data establish a critical role for histamine and H(1)R signaling in regulating T cell responses and susceptibility to CVB3-induced myocarditis in B6 mice. PMID- 22078273 TI - Biomechanical response of human spleen in tensile loading. AB - Blunt splenic injuries are most frequently caused as a result of motor vehicle collisions and are associated with high mortality rates. In order to accurately assess the risk of automotive related spleen injuries using tools such as finite element models, tissue level tolerance values and suitable material models must be developed and validated based on appropriate biomechanical data. This study presents a total of 41 tension tests performed on spleen parenchyma coupons and 29 tension tests performed on spleen capsule/parenchyma coupons. Standard dog bone coupons were obtained from fresh human spleen and tested within 48 h of death. Each coupon was tested once to failure at one of the four loading rates to investigate the effects of rate dependence. Load and acceleration data were obtained at each of the specimen grips. High-speed video and optical markers placed on the specimens were used to measure local displacement. Failure stress and strain were calculated at the location of failure in the gage length of the coupon. The results of the study showed that both the spleen parenchyma and the capsule are rate dependent, with higher loading rates yielding higher failure stresses and lower failure strains. The results also show that the failure stress of the splenic capsule is significantly greater than that of the underlying parenchyma. Overall, this study provides novel biomechanical data that demonstrate the rate dependent tissue level tolerance values of human spleen tissue in tensile loading, which can aid in the improvement of finite element models used to assess injury risk in blunt trauma. PMID- 22078274 TI - Axial speed of sound is related to tendon's nonlinear elasticity. AB - Axial speed of sound (SOS) measurements have been successfully applied to noninvasively evaluate tendon load, while preliminary studies showed that this technique also has a potential clinical interest in the follow up of tendon injuries. The ultrasound propagation theory predicts that the SOS is determined by the effective stiffness, mass density and Poisson's ratio of the propagating medium. Tendon stiffness characterizes the tissue's mechanical quality, but it is often measured in quasi-static condition and for entire tendon segments, so it might not be the same as the effective stiffness which determines the SOS. The objectives of the present study were to investigate the relationship between axial SOS and tendon's nonlinear elasticity, measured in standard laboratory conditions, and to evaluate if tendon's mass density and cross-sectional area (CSA) affect the SOS level. Axial SOS was measured during in vitro cycling of 9 equine superficial digital tendons. Each tendon's stiffness was characterized with a tangent modulus (the continuous derivative of the true stress/true strain curve) and an elastic modulus (the slope of this curve's linear region). Tendon's SOS was found to linearly vary with the square root of the tangent modulus during loading; tendon's SOS level was found correlated to the elastic modulus's square root and inversely correlated to the tendon's CSA, but it was not affected by tendon's mass density. These results confirm that tendon's tangent and elastic moduli, measured in laboratory conditions, are related to axial SOS and they represent one of its primary determinants. PMID- 22078275 TI - Mechanical coupling between transverse plane pelvis and thorax rotations during gait is higher in people with low back pain. AB - This study investigated whether people with low back pain (LBP) reduce variability of movement between the pelvis and thorax (trunk) in the transverse plane during gait at different speeds compared to healthy controls. Thirteen people with chronic LBP and twelve healthy controls walked on a treadmill at speeds from 0.5 to 1.72 m/s, with increments of 0.11 m/s. Step-to-step variability of the trunk, pelvis, and thorax rotations were calculated. Step-to step deviations of pelvis and thorax rotations from the average pattern (residual rotations) were correlated to each other, and the linear regression coefficients between these deviations calculated. Spectral analysis was used to determine the frequencies of the residual rotations, to infer the relation of reduced trunk variability to trunk stiffness and/or damping. Variability of trunk motion (thorax relative to pelvis) was lower (P=0.02), covariance between the residual rotations of pelvis and thorax motions was higher (P=0.03), and the linear regression coefficients were closer to 1 (P=0.05) in the LBP group. Most power of segmental residual rotations was below stride frequency (~1 Hz). In this frequency range, trunk residual rotations had less power than pelvis or thorax residual rotations. These data show that people with LBP had lower variability of trunk rotations, as a result of the coupling of deviations of residual rotations in one segment to deviations of a similar shape (correlation) and amplitude (regression coefficient) in the other segment. These results support the argument that people with LBP adopt a protective movement strategy, possibly by increased trunk stiffness. PMID- 22078276 TI - Antimicrobial susceptibility patterns and sensitivity to tulathromycin in goat respiratory bacterial isolates. AB - Bacterial pneumonia is a common and often life-threatening respiratory problem in both meat and dairy goats. Options for approved antibiotic therapy in goats to combat these bacterial infections are severely limited and frequently drugs must be used in an extra-label manner. Tulathromycin, a triamilide macrolide antimicrobial drug shown to be effective against swine and cattle respiratory bacterial agents, has been identified as a potentially useful drug in caprines. The present study was conducted to determine the susceptibility of recognized bacterial respiratory pathogens to commonly prescribed antimicrobials, with a particular emphasis on the efficacy of tulathromycin against these agents. Minimum inhibitory concentration (MIC) testing using microbroth dilution was performed on a collection of 45 Mannheimia haemolytica, 11 Pasteurella multocida, and 11 Bibersteinia trehalosi isolates from the lungs of goats with clinical pneumonia. To further characterize efficacy of tulathromycin against these pathogens, minimum bactericidal concentration (MBC) testing and kinetic killing assays were conducted. Most isolates were susceptible to the antimicrobials tested; however, increased resistance as demonstrated by higher MIC values was seen in all species to penicillin, in P. multocida to sulfadimethoxine, and in B. trehalosi to the tetracyclines. All isolates were susceptible to tulathromycin, which demonstrated a high killing efficiency in both bactericidal assays. Results of this study indicate that most goat pneumonic bacterial pathogens remain susceptible to commonly prescribed antibiotics, although some evidence of resistance was seen to certain drugs; and that tulathromycin is highly effective against goat respiratory pathogens which could make it a valuable medication in this species. PMID- 22078277 TI - Pestivirus and alphaherpesvirus infections in Swedish reindeer (Rangifer tarandus tarandus L.). AB - Herding semi-domesticated reindeer has economic and social value for Sami people in the northern territories of Fennoscandia. However, with the intensification of reindeer husbandry, interspecies transmission of pathogens between reindeer and domestic animals may become a problem, especially for countries such as Sweden, Norway, and Finland where pestivirus and alphaherpesvirus have been eradicated in domestic ruminants. This study, which included 1158 Swedish reindeer, showed relatively high prevalence of antibodies against bovine viral diarrhoea virus (BVDV) (32%) and bovine herpesvirus-1 (BoHV-1) (53%). Adult animals were more often seropositive for BVDV and BoHV-1 (50% and 78%, respectively) than were calves (18 and 11%, respectively). While the seroprevalence of alphaherpesvirus was similar in different herding districts, pestivirus seropositivity was highest in the South and diminished towards the North of the Swedish reindeer herding area. High correlation of the seropositivity against both pathogens at both individual and herd levels may indicate possible mutual synergetic effects and may be explained by the immunosuppressive nature of the viruses. While alphaherpesvirus seroprevalence was probably related to putative cervid herpesvirus 2 (CvHV-2), the pestivirus infecting reindeer remains undefined. The virus neutralisation test of reindeer sera using different pestivirus strains, revealed higher titres against Border disease virus strains like 137/4 (BDV-1) and Reindeer-1 (BDV-2) than against BVDV-1. However, the virus was not identified by real time RT-PCR in any of the samples (n=276) from seronegative reindeers. The study showed that pestivirus and alphaherpesvirus infections are endemic in the Swedish reindeer population. PMID- 22078278 TI - Are postoperative consequences of neoadjuvant chemotherapy for non-small cell lung cancer more severe in elderly patients? AB - OBJECTIVES: The purpose of this study was to assess the postoperative morbidity of patients >=75 years with non-small cell lung cancer (NSCLC) who underwent neoadjuvant chemotherapy, comparing them to younger patients. METHODS: We performed a case-control study over a 5-year period using Epithor, the French Society of Thoracic and Cardiovascular Surgery database, including to date more than 160,000 procedures from 103 institutions. We collected prospectively the data concerning 1510 patients with NSCLC who underwent preoperative chemotherapy, from January 2005 to December 2009. In order to compare patients with similar characteristics, we matched the 81 patients >=75 to 81 controls (<75) for gender, American Society of Anesthesia (ASA) score, Performance Status (PS), Forced Expiratory Volume (FEV1) and histological subtype of the tumor. The patients of the control group were randomized within the 1429 patients <75 included. Lung cancer surgical treatment, post-operative morbidity and mortality rates, and length of stay (LOS) were compared between the two age groups. RESULTS: There was no significant difference in type of resection between the two groups (p=0.07): pneumonectomy 15% (n=12) for patients >=75 vs 28% (n=23) for younger patients, lobectomy 65% (n=53) vs 54% (n=44), bilobectomy 14% (n=11) vs 6% (n=5) and sub lobar resection 4% (n=3) for the two groups. There was no significant difference in type of mediastinal lymphadenectomy (p=0.48) between the two age groups. Elderly patients presented a more important number of postoperative complications (p=0.04) and these ones were more severe (p=0.03). There was no significant difference in postoperative mortality with 30-day mortality: 4.9%, n=4, versus 2.5%, n=2, (p=0.83); 60-day mortality: 6.2%, n=5, versus 2.5%, n=2, (p=0.61); and 90-day mortality was the same. Hospital LOS was longer for the elderly (14.9 days, CI95%[12.5;17.4] vs 11.9 days, CI95%[10.7;13.3], p<0.001). CONCLUSION: Postoperative morbidity after neoadjuvant chemotherapy is more important in elderly patients. These data should be taken into account when considering the interest of preoperative treatment in elderly patients with resectable NSCLC. PMID- 22078279 TI - Purification of alginate and feasible production of monoclonal antibodies by the alginate-immobilized hybridoma cells. AB - Alginate has an extensive usage in the immobilization of many cell types. Although they have high biocompatibility, commercial alginates contain various degrees of contaminants such as polyphenols, endotoxins and proteins. Thus, these alginates show cytotoxicity against sensitive cell types such as hybridoma cells. In the studies so far, owing to this fact, commercially purchased high-priced ultrapure alginates have been used in the immobilization of hybridoma cells for monoclonal antibody production. However in this study, as a novelty, low-priced commercial alginate was purified, and then the cultivation of alginate immobilized hybridoma cells was performed for feasible monoclonal antibody production. Low-priced commercial alginate was purified with a profitability ratio of 40%. Then, an optimized immobilization procedure was conducted effectively by using the purified alginate. During more than 25 days of cultivation, serum concentration was kept low, and approximately 2 times greater monoclonal antibody production was achieved, in comparison with its free suspended counterpart. The results showed that the efficiency of monoclonal antibody production via alginate-immobilized hybridoma cultivation can be increased by performing a proved in-house purification method. By shedding light on the efficiency of the in-house purification method, the results also indicated a feasible way of monoclonal antibody production. PMID- 22078280 TI - Influence of mercury exposure on blood pressure, resting heart rate and heart rate variability in French Polynesians: a cross-sectional study. AB - BACKGROUND: Populations which diet is rich in seafood are highly exposed to contaminants such as mercury, which could affect cardiovascular risk factors OBJECTIVE: To assess the associations between mercury and blood pressure (BP), resting heart rate (HR) and HR variability (HRV) among French Polynesians METHODS: Data were collected among 180 adults (>= 18 years) and 101 teenagers (12 17 years). HRV was measured using a two-hour ambulatory electrocardiogram (Holter) and BP was measured using a standardized protocol. The association between mercury and HRV and BP parameters was studied using analysis of variance (ANOVA) and analysis of covariance (ANCOVA) RESULTS: Among teenagers, the high frequency (HF) decreased between the 2nd and 3rd tertile (380 vs. 204 ms2, p = 0.03) and a similar pattern was observed for the square root of the mean squared differences of successive R-R intervals (rMSSD) (43 vs. 30 ms, p = 0.005) after adjusting for confounders. In addition, the ratio low/high frequency (LF/HF) increased between the 2nd and 3rd tertile (2.3 vs. 3.0, p = 0.04). Among adults, the standard deviation of R-R intervals (SDNN) tended to decrease between the 1st and 2nd tertile (84 vs. 75 ms, p = 0.069) after adjusting for confounders. Furthermore, diastolic BP tended to increase between the 2nd and 3rd tertile (86 vs. 91 mm Hg, p = 0.09). No significant difference was observed in resting HR or pulse pressure (PP) CONCLUSIONS: Mercury was associated with decreased HRV among French Polynesian teenagers while no significant association was observed with resting HR, BP, or PP among teenagers or adults. PMID- 22078281 TI - [Managment of head and neck cancers during pregnancy]. AB - The coincidence of malignant disease during pregnancy is uncommon. The incidence of cancer in pregnancy has increased, due to the tendency to postpone childbirth to an older age. Cancer complicates approximately 0.1% of all pregnancies. Managing head and neck cancers during pregnancy requires additional pregnancy related understanding of the aetiological effect of pregnancy on cancer, knowledge of the direct and indirect effects of cancer on pregnancy, and the effect of diagnostic and treatment modalities on pregnancy. The timing of treatment is an important determinant on foetal wellbeing. A multidisciplinary approach should be adopted to enable parents and clinicians to make the best clinical decision. Clinicians must be cognizant with the ethical dilemmas of treatment. In head and neck cancers, pregnancy has no effect on maternal prognosis when compared to non-pregnant patients matched by age, cancer stage and treatment. PMID- 22078282 TI - Ocular vestibular evoked myogenic potentials to air conduction (AC oVEMP): useful in clinical practice? AB - Cervical vestibular-evoked myogenic potential (cVEMP) and ocular VEMP (oVEMP) stimuli can be used to measure otolith function using air (AC) and bone conducted (BC) stimuli. Cervical VEMPs reflect saccular function and can be recorded using air conduction (AC), whereas oVEMPs reflect probably predominantly utricular function. Air- and bone-conducted vibration can be used, because AC oVEMP methodology seems to be fast and simple in clinical practice to measure otolith function. In this study we discuss the advantages and problems of AC oVEMP stimulation. AC oVEMP can be easily and quickly obtained within a few seconds. N10 (first negative peak) and p15 (first positive peak) latencies may be used as parameters for clinical interpretation but amplitude fluctuations are relatively large. For daily clinical use of VEMP visualization in a normogram seems feasible. Especially the AC oVEMP methodology (100 dB nHL, tone burst 500 Hz) is fast and efficient in clinical practice to measure otolith function, predominantly utricular function. PMID- 22078283 TI - [Assessment of the efficiency of the auditory training in children with dyslalia and auditory processing disorders]. AB - AIM: To assess effectiveness of the auditory training in children with dyslalia and central auditory processing disorders. MATERIAL AND METHOD: Material consisted of 50 children aged 7-9-years-old. Children with articulation disorders stayed under long-term speech therapy care in the Auditory and Phoniatrics Clinic. All children were examined by a laryngologist and a phoniatrician. Assessment included tonal and impedance audiometry and speech therapists' and psychologist's consultations. Additionally, a set of electrophysiological examinations was performed - registration of N2, P2, N2, P2, P300 waves and psychoacoustic test of central auditory functions: FPT - frequency pattern test. Next children took part in the regular auditory training and attended speech therapy. Speech assessment followed treatment and therapy, again psychoacoustic tests were performed and P300 cortical potentials were recorded. After that statistical analyses were performed. RESULTS: Analyses revealed that application of auditory training in patients with dyslalia and other central auditory disorders is very efficient. CONCLUSIONS: Auditory training may be a very efficient therapy supporting speech therapy in children suffering from dyslalia coexisting with articulation and central auditory disorders and in children with educational problems of audiogenic origin. PMID- 22078284 TI - [Our experience in the treatment advanced neoplasms of floor of the mouth]. AB - AIM: The aim of this study was to evaluate results of our surgical treatment of advanced neoplasms of the floor of the mouth, treated from 2005-2011 in Department of Otolaryngology and Department of Plastic Surgery Medical University of Gdansk MATERIAL: We analyzed group of 12 patients (aged 36 to 70 years, mean 55) treated by primary surgical excision of neoplasms of the floor of the mouth (with tracheotomy and mandibulotomy) and selective or radical neck dissection (uni- or bilateral) in combination with chemoradiotherapy. All patients referees with advancement of locoregional disease: primary tumors (T3 or T4) and neck metastases (N1 or N2b) Most of the patients required to use free microvascular reconstruction with free forearm skin flaps. Histological examinations revealed squamous cell carcinoma (11/12) and adenocarcinoma (1/12). RESULTS: Two patients die in 1 and 4 months after surgery. Three die from 2 to 3 years after surgery. Rest live from 6 month to 6 year after therapy. CONCLUSION: Free forearm skin microvascular flap is good (anatomical and functional) for reconstruction for large defects after resection neoplasms of the floor of the mouth. PMID- 22078285 TI - [Major salivary gland disorders in children and adolescents]. AB - The aim of this study was a review of 67 children treated for salivary gland tumors in the ENT Department Medical University of Gdansk since 1974 to 2008. In that group we observed 52 children with tumor of the parotid gland, 13 with tumor of submandibular gland and 2 with subligual gland tumors. Tumor-like lesions were stated the largest group of tumors and were observed in 33 (49%) of children, mainly of chronic sialadenitis (17 cases). Predominant number of tumors was observed in scholarship children. The most common symptoms were slow enlargement of tumor and swelling of the salivary gland. In the group of benign tumors most common was pleomorphic adenoma (19 cases) and in the group of malignant tumors most common was clear cell carcinoma (2 cases) and rhabdomyosarcoma (2 cases). In this report the authors describe basic epidemiological and clinical data (age, sex, duration of symptoms, histological structure of tumor, diagnostic methods, methods and results of treatment) and observations connected with differences of salivary gland tumors in that group of patients. PMID- 22078286 TI - [The analysis of mean arterial pressure and heart rate in patients treated with laryngological surgery within pre- and peri- and postoperative periods]. AB - INTRODUCTION: This work aimed to analyse the mean arterial blood pressure (MBP) and heart rate (HR) in patients who underwent laryngological surgery within the preoperative, perioperative and postoperative periods. MATERIAL AND METHODS: The study covered 502 patients, including 209 women and 293 men, aged 18-85, who were divided into 6 groups according to the type of surgery: I - FESS (Functional Endoscopic Sinus Surgery), II - septoplasty, III - endoscopic re-operation of the paranasal sinuses, IV - microlaryngoscopy, V - tonsillectomy, VI - middle ear surgery. Only the patients with BP below 140/90 mmHg and maximum class 2 in the ASA scale were qualified for the surgical procedure. On admission, the arterial blood pressure was measured and diagnostic investigations like FBC, blood grouping determination, coagulogram, ESR, CRP and imaging studies were performed in each patient. Every operation was conducted under TIVA. BT and HR were monitored during an operation as well as through the four following hours in a recovery room. RESULTS: The youngest group of patients with chronic palatine tonsillitis showed the lowest pressure values while the oldest studied group consisted of patients who were operated due to chronic otitis media and this group demonstrated the highest BP values. The patients with treated or untreated hypertension should be pharmacologically normalised by an anaesthesiologist. However, considerable lowering of BP can often be not possible, contrary to the patients with normal BP. CONCLUSIONS: The own experience indicates that perioperative lowering of BP, including hypotension, ought to be avoided in cardiology patients. The postoperative BP raise, usually accompanied by pain, was noticed in the own studies. Therefore, effective analgesic treatment should be implemented in a recovery room. PMID- 22078287 TI - [The results and toxicity of organ preservation treatment for locoregionally advanced laryngeal and hypopharyngeal cancer]. AB - The most frequent malignant tumor of the head and neck region is a squamous cell cancer of the larynx. Squamous cell cancer of the hypopharynx is diagnosed rarely, but it has poorer prognosis than laryngeal cancer. The surgical treatment, especially in advanced disease, is a laryngectomy with the definitive tracheostomy, what negatively influenced the quality of life. Therefore, oncologists have been interested in new alternative methods of conservative treatment from many years. THE AIM OF THE STUDY: The evaluation of efficacy and toxicity of the organ preservation treatment in patients with locally advanced laryngeal and hypopharyngeal cancer. MATERIAL AND METHODS: The patients with diagnosed squamous cell laryngeal and hypopharyngeal cancer in III and IVa clinical status were treated with concomitant radiochemotherapy with intention of the organ preservation. Conformal 3D radiotherapy and SIB-IMRT technique was applied in all cases. Concomitant chemotherapy consisted of cisplatin in daily dose100mg/m(2) given two times during irradiation (1 and 22 day of treatment) or once weekly in dose 40mg/m(2). Between January 2004 and November 2008 146 patients were treated with this method. There were 83 patients diagnosed with laryngeal cancer and 62 patients with hypopharyngeal cancer in this group. RESULTS: The median follow up is 42 months. Five years overall survival is 75% and disease free survivak is 63%. Three years laryngectomy free survival (LFS) is 82% and 5-years LFS is 76%. This group of patients is alive with larynx preservations. In 17.3% patients local recurrence was observed (4.5% regional recurrence and 1.8% locoregional). Those patients underwent salvage surgery or were treated with palliative chemotherapy. No severe life risking early and late complications were observed. Only 7% of patients have required temporary tracheostomy because of difficulties in breathing due to larynx edema. CONCLUSION: We can conclude that organ preservation treatment is a valuable alternative to surgical procedure in patients diagnosed with laryngeal and hypopharyngeal cancer in III and IVa clinical status. PMID- 22078288 TI - [Fungal rhinosinusitis - still unsolved problem]. AB - Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the nose and paranasal sinuses. Fungi are considered to be one of the pathogens responsible for some kinds of CRS. Fungal rhinosinusitis - the classifications schemes, the diagnostic criteria and methods of treatment are still being discussed. 338 patients underwent the endoscopic sinus surgery due to CRS in the Otolaryngology Department of the Medical University of Lodz in the years 2009-2011 (February). The histopathological examination revealed fungi only in three patients. The authors report three cases of patients with fungal rhinosinustis - the fungal ball of the sphenoid sinus in one patients, the fungal ball of the maxillary sinus in the second one and non-invasive fungal rhinosinusitis. The different classifications and diagnostic criteria are also presented. Based on the publications using updated diagnostic standards and sensitive techniques to detect fungi, a higher number of patients can now be diagnosed with fungal rhinosinusitis. PMID- 22078289 TI - [Diagnostic difficulties of the patient with sinonasal tract tumor; therapeutic dilemmas - a case report and up to date review]. AB - Esthesioneuroblastoma (ENB) is a rare malignancy unique to the sinonasal tract. It arises from the olfactory epithelium and has a tendency to originate from one side of the nasal cavity and paranasal sinuses with frequent extension into the cranial cavity and orbit. There is a bimodal age distribution between 11 and 20 years and between 51 and 60 years. ENB accounts for approximately 2-3% of intranasal cancers. Due to the non-specific nature of the initial presentation and slow growth of the tumor, patients often have a long history before diagnosis. Physicians including pathologists are not always aware of distinctive features of ENB especially radiographic, histologic and immunohistochemical characteristics. Additional difficulty can be the fact that Esthesioneuroblastoma can histologically mimic many tumors within the sinonasal tract. We report on a 38-year-old male patient with a Kadish stage C tumor with frontal lobe invasion. The patient underwent a craniofacial resection with a combined head neck and neurosurgeon team. After the surgery postoperative radiotherapy was used. The aim of this study is to present the natural history of the malignancy, the diagnostic process, treatment and prognosis, based on the literature review. PMID- 22078290 TI - Histologic abnormalities of placental tissues in Fabry disease: a case report and review of the literature. AB - Fabry disease is an X-linked lysosomal storage disease caused by deficiency of alpha-galactosidase A, resulting in the accumulation of globotriaosylceramide. Many women experience symptoms, but the understanding of placental and fetal aspects of the disease is limited. We report the pregnancy outcome in and placental pathology of a 37-year-old woman with Fabry disease. She became pregnant 2 years after starting enzyme replacement therapy and continued therapy throughout her pregnancy. At 38 weeks' gestation, she gave birth to a healthy boy with the same maternal Fabry mutation. The present case describes more extensive placental involvement by Fabry disease than has been previously reported. Globotriaosylceramide deposits were found within multiple cell types of the placenta, cord, and membranes. Because of the small numbers of cases described in the literature for comparison, it remains unclear if placental tissues are also targeted by enzyme replacement therapy. PMID- 22078291 TI - Relationship between alpha-methylacyl-coenzyme A racemase expression and mucin phenotype in gastric cancer. AB - Alpha-methylacyl-coenzyme A racemase controls beta-oxidation of branched-chain fatty acid and their derivatives. Many investigators have described alpha methylacyl-coenzyme A racemase expression in various neoplasias and their precursor lesions. Although there have been a few reports regarding alpha methylacyl-coenzyme A racemase expression in gastric neoplasia, these reports did not discuss the relationship between alpha-methylacyl-coenzyme A racemase expression and mucin phenotype. This study analyzed alpha-methylacyl-coenzyme A racemase expression of gastric carcinomas with regard to mucin phenotype. Alpha methylacyl-coenzyme A racemase expression was evaluated in 85 cases of gastric biopsies including gastric epithelial neoplasia and nonneoplasia and in 108 cases of surgically resected early gastric cancer. In biopsy cases, alpha-methylacyl coenzyme A racemase was more highly expressed in neoplasia (69.7%, 23/33) than in nonneoplasia (0%, 0/42) (P = .001). Alpha-methylacyl-coenzyme A racemase was overexpressed in 20.0% (2/10) of cases that were indefinite for neoplasia, and the 2 positive cases were ultimately diagnosed as adenocarcinoma. In resected cases of early gastric adenocarcinoma, alpha-methylacyl-coenzyme A racemase expression significantly correlated with mucin phenotype (P = .003), but not with tumor progression, histologic classification, or clinicopathologic features. Alpha-methylacyl-coenzyme A racemase expression was significantly higher in intestinal-phenotype carcinoma (90.2%, 37/40) than in gastric-phenotype carcinoma (56.3%, 18/31) (P = .006) and also correlated with an increase in CDX2 expression (P = .018) and a decrease in MUC5AC expression (P = .048). This tendency was observed in all histologic types. Our results indicate that alpha-methylacyl coenzyme A racemase is a useful marker for distinguishing gastric neoplasia from nonneoplasia even at an early stage. Alpha-methylacyl-coenzyme A racemase expression is associated with mucin phenotypes of gastric neoplasia, particularly with the expression of CDX2 and MUC5AC. PMID- 22078292 TI - Efficient alpha, beta-motif finder for identification of phenotype-related functional modules. AB - BACKGROUND: Microbial communities in their natural environments exhibit phenotypes that can directly cause particular diseases, convert biomass or wastewater to energy, or degrade various environmental contaminants. Understanding how these communities realize specific phenotypic traits (e.g., carbon fixation, hydrogen production) is critical for addressing health, bioremediation, or bioenergy problems. RESULTS: In this paper, we describe a graph-theoretical method for in silico prediction of the cellular subsystems that are related to the expression of a target phenotype. The proposed (alpha, beta) motif finder approach allows for identification of these phenotype-related subsystems that, in addition to metabolic subsystems, could include their regulators, sensors, transporters, and even uncharacterized proteins. By comparing dozens of genome-scale networks of functionally associated proteins, our method efficiently identifies those statistically significant functional modules that are in at least alpha networks of phenotype-expressing organisms but appear in no more than beta networks of organisms that do not exhibit the target phenotype. It has been shown via various experiments that the enumerated modules are indeed related to phenotype-expression when tested with different target phenotypes like hydrogen production, motility, aerobic respiration, and acid tolerance. CONCLUSION: Thus, we have proposed a methodology that can identify potential statistically significant phenotype-related functional modules. The functional module is modeled as an (alpha, beta)-clique, where alpha and beta are two criteria introduced in this work. We also propose a novel network model, called the two-typed, divided network. The new network model and the criteria make the problem tractable even while very large networks are being compared. The code can be downloaded from http://www.freescience.org/cs/ABClique/ PMID- 22078293 TI - The removal of post-sclerotherapy pigmentation following sclerotherapy alone or in combination with crossectomy. AB - BACKGROUND: Sclerotherapy is a widely used method for the obliteration of blood vessels. Hyperpigmentation is a frequent complication that results from haemosiderin (FeO) accumulation. Hyperpigmentation and changes in the skin can be observed with ultrasound. OBJECTIVE: The aim of this study was to evaluate the efficacy of hyperpigmentation elimination using an intense pulse light generator (IPL) equipped with radio waves (RF) under ultrasonography (US) control. METHODS: Twenty-one women with permanent hyperpigmentation (after sclerotherapy or crossectomy combined with sclerotherapy) underwent a hyperpigmentation eliminating therapy with the use of IPL + RF and were monitored by using US. The thicknesses of the dermis and the subcutaneous tissue as well as the echogenicities of each layer were assessed. RESULTS: As a result of the therapy, a complete regression of hyperpigmentation was achieved in 90.48% of the women, and in 9.52% of the women, the therapy led to a reduction in hyperpigmentation but did not cause its complete disappearance. An increase in dermal echogenicity and a decrease in subcutaneous tissue echogenicity were observed, but there was no change in their thicknesses. After the therapy, the ultrasound images of areas of previous hyperpigmentation corresponded with images that were characteristic of healthy skin. CONCLUSION: IPL + RF therapy is effective for eliminating permanent skin hyperpigmentation after sclerotherapy. US is also useful in this therapeutic method. PMID- 22078294 TI - Angioplasty of below-the-elbow arteries in critical hand ischaemia. AB - BACKGROUND: Critical hand ischaemia (CHI) due to pure below-the-elbow (BTE) artery obstruction is a disabling disease and there is still no consensus concerning the most appropriate revascularisation strategy. The aim of this study was to assess the feasibility, safety and outcomes of percutaneous transluminal angioplasty (PTA) in the treatment of CHI due to pure BTE artery disease. METHODS AND RESULTS: Twenty-eight patients (age 62 +/- 11 years; three females) with a total of 34 hands affected by CHI (one pain at rest; 18 non-healing ulcer; 15 gangrene) due to pure BTE artery disease underwent PTA. Most of the patients were males with a long history of diabetes mellitus, end-stage renal disease (ESRD) on haemodialysis and systemic atherosclerosis. The interosseous artery was free of disease in all cases, whereas the radial and ulnar arteries were simultaneously involved in 31/34 hands with long stenosis/occlusions (91%; mean length 155 +/- 64 mm). The technical success rate was 82% (28/34), with only three minor complications. In the three cases with a functioning radial arteriovenous fistula, we successfully treated the ulnar artery. PTA was unsuccessful in 18% (6/34) hands due to inability to cross severely calcified lesions. The hand healing rate was 65% (22/34). The predictors of hand healing were PTA technical success (odds ratio (OR) 0.5, confidence interval (CI) 0.28-0.88; p <= 0.0001) and digital run-off (OR 0.37, CI 0.19-0.71; p <= 0.003). The mean follow-up period was 13 +/- 9 months. Six patients (18%) underwent secondary procedures due to symptomatic restenosis. In all these cases, a successful re-PTA was performed at a mean 6 months after the index procedure, and there were no major procedure related events. Ten patients (36%) died during follow-up. CONCLUSIONS: Angioplasty of BTE vessels for CHI is a feasible and safe procedure with acceptable rates of technical success and hand healing. Poor digital run-off due to obstructive disease of the digital vessels can reduce the hand-healing rate after a successful PTA. Pure isolated BTE vessel disease seems to characterise patients with ESRD and diabetes mellitus. PMID- 22078295 TI - Priming of spatial distance enhances children's creative performance. AB - According to construal level theory, psychological distance promotes more abstract thought. Theories of creativity, in turn, suggest that abstract thought promotes creativity. Based on these lines of theorizing, we predicted that spatial distancing would enhance creative performance in elementary school children. To test this prediction, we primed spatial distance by presenting 6- to 9-year-olds with pictures of increasingly distal objects (from their own desk to the galaxy) or increasingly proximal objects (from the galaxy to their own desk) and then assessed the fluency and originality of their ideas in a creativity test. We found, consistent with the hypothesis, that after priming of spatial distance, compared with priming of spatial proximity, children were more creative, as reflected in higher scores of both fluency and originality. This result was not qualified by children's age or gender. PMID- 22078296 TI - Cerebral thrombosis complicating Crohn's disease: two cases. AB - Cerebrovenous thrombosis is quite rare in infammatory bowel disease. There are only a few reports of this association in the literature. We report 2 cases of patients with Crohn's disease (CD) who developed cerebral thrombophlebitis confirmed by neuroimaging. The first case was a 35-year-old man with a history of CD who presented with acute confusion. Brain magnetic resonance imaging demonstrated a left temporoparietal infarction and thrombosis of the left lateral sinus. Coagulation studies showed a marked protein S deficiency. His condition improved significantly after initiation of anticoagulant therapy. The second case was a 38-year-old woman who was admitted for a sudden loss of consciousness with tetraplegia. Brain computed tomography revealed a profound cerebrovenous thrombosis. She died within a few days after admission. Inflammatory bowel disease carries an increased risk of venous and arterial thrombosis. Although the pathogenic mechanisms of this predisposition are unclear, a possible role of inherited risk factors for thrombosis in determining this predisposition has been suggested. In these cases, both fibrinolysis and coagulation are activated as well. PMID- 22078297 TI - Tissue inhibitors of metalloproteinases. AB - Orchestration of the growth and remodeling of tissues and responses of cells to their extracellular environment is mediated by metalloproteinases of the Metzincin clan. This group of proteins comprises several families of endopeptidases in which a zinc atom is liganded at the catalytic site to three histidine residues and an invariant methionine residue. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous protein regulators of the matrix metalloproteinase (MMPs) family, and also of families such as the disintegrin metalloproteinases (ADAM and ADAMTS). TIMPs therefore have a pivotal role in determining the influence of the extracellular matrix, of cell adhesion molecules, and of many cytokines, chemokines and growth factors on cell phenotype. The TIMP family is an ancient one, with a single representative in lower eukaryotes and four members in mammals. Although much is known about their mechanism of action in proteinase regulation in mammalian cells, less is known about their functions in lower organisms. Recently, non-inhibitory functions of TIMPs have been identified in mammalian cells, including signaling roles downstream of specific receptors. There are clearly still questions to be answered with regard to their overall roles in biology. PMID- 22078298 TI - Neuroimmune modulation following traumatic stress in rats: evidence for an immunoregulatory cascade mediated by c-Src, miRNA222 and PAK1. AB - BACKGROUND: Neuroimmune modulation following traumatic stress is accompanied by cortical upregulation of c-Src expression, but the mechanistic details of the potential regulatory link between c-Src expression and immunosuppression have not been established. METHODS: We used a combination of techniques to measure temporal changes in: (i) the parallel expression of c-Src and microRNA222; (ii) levels of PAK1 (p21-activated kinase 1); and (iii) the association between PAK1 and interleukin 1beta signaling, both in cortex of rats following traumatic stress and in primary cortical neurons. Techniques included real-time PCR, immunoprecipitation, western blotting and subcellular fractionation by discontinuous centrifugation. We also measured lymphocyte proliferation and natural killer (NK) cell activity. RESULTS: We confirm robust upregulation of c Src expression following traumatic stress. c-Src upregulation was accompanied by marked increases in levels of miRNA222; other studied miRNAs were not affected by stress. We also established that PAK1 is a primary target for miRNA222, and that increased levels of miRNA222 following traumatic stress are accompanied by downregulation of PAK1 expression. PAK1 was shown to mediate the association of IL-1RI with lipid rafts and thereby enhance IL-1 signaling. Detailed analyses in cultured neurons and glial cells revealed that PAK1-mediated enhancement of IL 1RI activation is governed to a large extent by c-Src/miRNA222 signaling; this signaling played a central role in the modulation of lymphocyte proliferation and NK cell activity. CONCLUSIONS: Our results suggest that neuroimmune modulation following traumatic stress is mediated by a cascade that involves c-Src-mediated enhancement of miRNA222 expression and downregulation of PAK1, which in turn impairs signaling via IL-1beta/IL1-RI, leading to immunosuppression. The regulatory networks involving c-Src/miRNA222 and PAK1/IL-1RI signaling have significant potential for the development of therapeutic approaches designed to promote recovery following traumatic injury. PMID- 22078299 TI - An evolutionary based social rank explanation of why low income predicts mental distress: a 17 year cohort study of 30,000 people. AB - BACKGROUND: This paper presents a new psychological model of why low income increases risk of mental distress. Consistent with evolutionary perspectives on disorder, income was predicted to relate to mental distress only through acting as an indirect proxy for social rank. METHODS: Participants were part of a longitudinal cohort sample of 30,000 people who were representative of the British population and who completed measures annually for up to 17 years. Mental distress was assessed via the General Health Questionnaire which measures anxiety, depression, and general functioning. RESULTS: Both income and the rank of the income within the region (and the rank of income within other comparison groups, such as similar individuals) predicted current and future distress. However, when distress was jointly regressed on income and income rank, only income rank remained a significant predictor. LIMITATIONS: The outcome measure was self-report (although the predictor was objective). CONCLUSIONS: The results support psychosocial rather than material explanations of why income relates to distress, and suggest that a concern for social rank is the mechanism through which these effects occur. This mechanism is consistent with an evolutionarily based "involuntary defeat syndrome" where hard wired responses to low social rank increase risk for disorder and the Decision by Sampling model of how people make relative judgments. Negative cognitions associated with low social rank (particularly defeat and entrapment) may be clinically targetable in both prevention and treatment programs to reduce socio-economic mental health disparities. PMID- 22078301 TI - Response of spermatozoa from the emu (Dromaius novaehollandiae) to rapid cooling, hyperosmotic conditions and dimethylacetamide (DMA). AB - Three experiments conducted to improve the survival of emu sperm during cryopreservation aimed to: (1) minimize chilling injury during the cooling phase; (2) determine the osmotic effects of dimethylacetamide (DMA), sucrose and trehalose; and (3) investigate the timing and nature of cryoprotectant toxicity. We measured sperm membrane integrity, motility, morphology and egg membrane penetration. In Experiment 1, semen diluted 1:1 with a pre-cooled diluent (5 degrees C) prevented chilling injury. In Experiment 2, semen was diluted with DMA, trehalose or sucrose (300-2400mOsm/L) in deionized water. Only added DMA decreased the percentage of morphologically normal sperm. The percentage of motile sperm was higher with DMA than with the sugars, but membrane intact sperm were comparable amongst all cryoprotectants. As for the osmotic effects, the percentage of membrane intact sperm decreased with 2400mOsm/L and sperm motility decreased with 1200-2400mOsm/L, but sperm morphology was similar at all osmolarities. In Experiment 3, sperm membrane integrity, motility and morphology were comparable at all DMA osmolarities between sperm equilibrated for 0 and 15min, and remained unchanged after removal of DMA. We conclude that: (a) loss of sperm function during the cooling phase can be avoided by using a diluent maintained at 5 degrees C; (b) emu spermatozoa tolerate upto 1400mOsm/L; (c) DMA results in a permanent change in sperm morphology when it is dissolved in deionized water, but does not alter sperm membrane integrity and motility; and (d) equilibration time of sperm with DMA can be less than 10min. PMID- 22078300 TI - Functional near-infrared spectroscopy (fNIRS) of brain function during active balancing using a video game system. AB - Functional near-infrared spectroscopy (fNIRS) is a portable, non-invasive, brain imaging technology that uses low levels of non-ionizing light to record changes in cerebral blood flow in the brain through optical sensors placed on the surface of the scalp. These signals are recorded via flexible fiber optic cables, which allow neuroimaging experiments to be conducted on participants while performing tasks such as standing or walking. FNIRS has the potential to provide new insights into the evolution of brain activation during ambulatory motor learning tasks and standing tasks to probe balance and vestibular function. In this study, a 32 channel fNIRS system was used to record blood flow changes in the frontal, motor, sensory, and temporal cortices during active balancing associated with playing a video game simulating downhill skiing (Nintendo WiiTM; Wii-fitTM). Using fNIRS, we found activation of superior temporal gyrus, which was modulated by the difficulty of the balance task. This region had been previously implicated in vestibular function from other animal and human studies. PMID- 22078302 TI - Obstetrical outcome valuations by patients, professionals, and laypersons: differences within and between groups using three valuation methods. AB - BACKGROUND: Decision-making can be based on treatment preferences of the patient, the doctor, or by guidelines based on lay people's preferences. We compared valuations assigned by three groups: patients, obstetrical care professionals, and laypersons, for health states involving both mother and (unborn) child. Our aim was to compare the valuations of different groups using different valuation methods and complex obstetric health outcome vignettes that involve both maternal and neonatal outcomes. METHODS: Patients (n = 24), professionals (n = 30), and laypersons (n = 27) valued the vignettes using three valuation methods: visual analogue scale (VAS), time trade-off (TTO), and discrete choice experimentation (DCE). Each vignette covered five health attributes: maternal health ante partum, time between diagnosis and delivery, process of delivery, maternal outcome, and neonatal outcome. We used feasibility questionnaires, Generalization theory, test retest reliability and within-group reliability to compare the valuation patterns between groups and methods. We assessed relative weights from each valuation method to test for consistency across groups. RESULTS: Test-retest reliability was equal across groups, but different across methods: highest for VAS (ICC = 0.61-0.73), intermediate for TTO (ICC = 0.24-0.74) and lowest for DCE (kappa = 0.15-0.37). Within-group reliability was highest in all groups with VAS (ICC = 0.70-0.73), intermediate with DCE (kappa = 0.56-0.76) and lowest with TTO (ICC = 0.20-0.66). Effects of groups were smaller than effects of methods. Differences between groups were largest for severe health states. CONCLUSION: Based on our results, decision making among laypersons should use TTO or DCE; patients should use VAS or TTO. PMID- 22078303 TI - Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia. AB - BACKGROUND: Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs). METHODS: We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross validation procedures. RESULTS: The 5 independent nsSNPs with false discovery rate q <= .25, as well as 13 additional nsSNPs at p < .01 and located in functional candidate genes, were genotyped in the replication samples. One SNP, rs13107325, located at the metal ions transporter gene SLC39A8, reached significance in the combined sample after Bonferroni correction (trend test, p = 2.7 * 10(-6), allelic odds ratio = 1.32). This SNP presents minor allele frequency of 5% to 10% in many European populations but is rare outside Europe. We also confirmed the polygenic component of susceptibility. CONCLUSIONS: Taking into account that another metal ions transporter gene, SLC39A3, is associated to bipolar disorder, our findings reveal a role for brain metal homeostasis in psychosis. PMID- 22078304 TI - Human proteome analysis by using reversed phase monolithic silica capillary columns with enhanced sensitivity. AB - We have developed one-dimensional liquid chromatography-tandem mass spectrometry systems with meter-scale reversed phase monolithic silica-C18 capillary columns for human proteome analysis. When tryptic peptides from 4 MUg HeLa cell lysate proteins were directly injected onto a 4-m, 100 MUm i.d. monolithic silica-C18 column and an 8-h gradient was applied at 500 nL/min, 41,319 non-redundant tryptic peptides from 5,970 proteins were successfully identified from quadruplicate measurements; this is the best result yet reported without the use of exhaustive pre-fractionation. Because separation efficiency in the 4-m long monolithic column system (8-h gradient, 26,805 peptides identified on average) was much higher than that in a 15-cm long, conventional particle-packed column system (65-min gradient, 10,183 peptides identified), ion suppression caused by co-elution of peptides was drastically reduced, resulting in a 5-fold improvement in MS responses on average. However, we did not observe dynamic range extension for the identified human peptides, whereas 78-fold extension was observed in our previous analysis of the Escherichia coli proteome (Anal. Chem., 82 (2010) 2616). This was probably because the current analytical technologies are still not adequate to allow acquisition of MS/MS spectra for detected precursor ions from highly complex human peptide mixtures, even though MS sensitivity was enhanced by the improved separation in this LC system. More efficient LC separation and faster MS/MS scanning are still needed for complete human proteome analysis. PMID- 22078305 TI - The offline combination of thin-layer chromatography and high-performance liquid chromatography with diode array detection and micrOTOF-Q mass spectrometry for the separation and identification of spinochromes from sea urchin (Strongylocentrotus droebachiensis) shells. AB - Thin-layer chromatography (TLC) with off-line high-performance liquid chromatography coupled to diode array detection and micrOTOF-Q mass spectrometry (HPLC-DAD-MS) resulted in the successful fractionation, separation and identification of spinochrome pigments from sea urchin (Strongylocentrotus droebachiensis) shells. Two fractions of pigments were separated by TLC and eluted with methanol using a TLC-MS interface. HPLC-DAD-MS analysis of the fractions indicated the presence of six sea urchin pigments: spinochrome monomers B and D, three spinochrome dimers (anhydroethylidene-6,6'-bis(2,3,7 trihydroxynaphthazarin) and its isomer and ethylidene-6,6'-bis(2,3,7 trihydroxynaphthazarin)), and one pigment that was preliminary identified as a spinochrome dimer with the structural formula C(22)H(16)O(16). PMID- 22078306 TI - Management of perioperative endoleaks during endovascular treatment of juxta renal aneurysms. AB - BACKGROUND: Evolution of stentgraft and vascular imaging technologies allows endovascular treatment (ET) of juxta-renal aneurysms (JRA). However, endoleaks rates and implants stability are not well documented. The aim of this study was to report the incidence and the perioperative treatment of the endoleaks occurring during ET for JRA. MATERIAL AND METHODS: Between January 2000 and April 2010, a total of 957 treated aneurysms were prospectively collected in a database. ET cases for JRA were selected from this database. Pre- and postoperative imaging was retrospectively analyzed to determine the incidence, localization, and treatment of the endoleaks detected following this technique. RESULTS: The series included 50 patients (5%; age, 73 +/- 12 years; 44 men). Mean diameter was 60 +/- 12 mm. The ET included 38 fenestrated and/or branched endografts and 12 endografts implanted according to the chimney technique. One hundred and forty-three target vessels were perfused. Immediately after endograft deployment, angiography showed endoleaks in 15 patients (30%): 11 type Ia, 1 type II, and 3 type III endoleaks. These endoleaks were treated by aortic endograft modeling and/or stenting in 11 patients, and by placing an aortic extension in two patients. Despite modeling, two patients had a persistent type Ia endoleak and were respectively treated by placing a Palmaz stent and by performing proximal embolization. Despite these procedures, completion angiography showed five residual endoleaks (10%): two type Ia, two type II, and one type III. Immediate postoperative computed tomography (CT) angiography showed endoleaks in 13 patients (28%): six type I, six type II, and one mixed type II/III. Among these 13 patients, on the initial angiography, nine presented with an endoleak, three with a type II and one with a type Ib. Early mortality (<30 days) was 8% (four patients). With a mean follow-up of 12 months, (range, 1-42), six patients presented with a persisting endoleak (four type II, one type Ia, and one multiple type). Aneurysm growth (>=5 mm) was reported in two patients (4%), and nine secondary endovascular procedures were performed to treat these endoleaks. CONCLUSION: Endoleaks are frequent during ET of JRA. They are treated not only according to their type but also according to the implant characteristics (fenestrated or chimney). Although most endoleaks can be perioperatively treated with simple endovascular means, treatment of persisting type Ia endoleaks remains challenging. PMID- 22078307 TI - Positive selection on a bacterial oncoprotein associated with gastric cancer. AB - BACKGROUND: Helicobacter pylori is a vertically inherited gut commensal that is carcinogenic if it possesses the cag pathogenicity island (cag PaI); infection with H.pylori is the major risk factor for gastric cancer, the second leading cause of death from cancer worldwide (WHO). The cag PaI locus encodes the cagA gene, whose protein product is injected into stomach epithelial cells via a Type IV secretion system, also encoded by the cag PaI. Once there, the cagA protein binds to various cellular proteins, resulting in dysregulation of cell division and carcinogenesis. For this reason, cagA may be described as an oncoprotein. A clear understanding of the mechanism of action of cagA and its benefit to the bacteria is lacking. RESULTS: Here, we reveal that the cagA gene displays strong signatures of positive selection in bacteria isolated from amerindian populations, using the Ka/Ks ratio. Weaker signatures are also detected in the gene from bacteria isolated from asian populations, using the Ka/Ks ratio and the more sensitive branches-sites model of the PAML package. When the cagA gene isolated from amerindian populations was examined in more detail it was found that the region under positive selection contains the EPIYA domains, which are known to modulate the carcinogenicity of the gene. This means that the carcinogenicity modulating region of the gene is undergoing adaptation. The results are discussed in relation to the high incidences of stomach cancer in some latin american and asian populations. CONCLUSION: Positive selection on cagA indicates antagonistic coevolution between host and bacteria, which appears paradoxical given that cagA is detrimental to the human host upon which the bacteria depends. This suggests several non-exclusive possibilities; that gastric cancer has not been a major selective pressure on human populations, that cagA has an undetermined benefit to the human host, or that horizontal transmission of H.pylori between hosts has been more important in the evolution of H.pylori than previously recognized, reducing the selective pressure to lower the pathogenicity of the bacteria. The different patterns of adaptation of the gene in different human populations indicates that there are population specific differences in the human gut environment - due either to differences in host genetics or diet and other lifestyle features. PMID- 22078308 TI - [Preliminary validation of the Simulap((r)) physical simulator and its assessment system for laparoscopic surgery]. AB - INTRODUCTION: Our aim is to assess the face and content validities of the physical simulator Simulap((r)), as well as the construct validity of its assessment method. MATERIAL AND METHODS: Five novice surgeons (G1) and five experts (G2) performed seven basic tasks and one suturing exercise on Simulap((r)), which were assessed through an exam based on mistakes and performance time. Face and content validations were carried out by novice surgeons and expert surgeons, respectively. Both validations consisted of a questionnaire graded on a five-point scale about the Simulap((r)) and its tasks. Construct validity of the assessment system was determined by comparing the scores of both groups. RESULTS: Surgeons rated the Simulap((r)) simulator and its training program positively, obtaining an average score of 4+/-1.1 for G1 and of 4.9+/-0.6 for G2. G2 considered training on Simulap((r)) very useful for the training of residents and surgeons, obtaining a maximum score of 5. G2 outperformed G1 in all task scores, with statistically significant differences in the eye-hand coordination (G1: 52.2+/-6.7 vs. G2: 39.6+/-6.5; P=.027), dissection (G1: 301.8+/-100.2 vs. G2: 150.8+/-66.7; P=.028) and suturing exercises (G1: 258.5+/-87.0 vs. G2: 108.4+/-20.2; P=.009). CONCLUSIONS: The assessment method for Simulap((r)) is able to distinguish different levels of experience in laparoscopic surgery. Furthermore, this simulator showed a great acceptance by surgeons for the learning of basic skills. PMID- 22078309 TI - Emergency medical dispatch - more than merely sending the ambulance! PMID- 22078310 TI - Early human dispersals into the Iberian Peninsula: a comment on Martinez et al.(2010) and Garcia et al. (2011). AB - Garcia et al. (2011) recently discussed early human dispersals into the Iberian Peninsula, describing several putative lithic artifacts (Martinez et al., 2010) recovered from layer 7 of the Vallpara dissection (Madurell-Malapeira et al., 2010) in Terrassa (Valles-Penedes Basin, Catalonia, Spain). According to the authors' opinion, such evidence (1) fills a gap in the chronology of early human occupation in Iberia, (2) indicates that these populations had primary and early access to carcasses, and (3) confirms that early human populations were equipped with advanced cultural traits enabling them to survive in unfavourable climatic conditions. We argue below that the record of human activity at Vallparadis (Martinez et al., 2010;Garcia et al., 2011) is doubtful and even that if confirmed, a chronological gap would remain (contra Garcia et al., 2011). Additional remarks on assertions by these authors on the Vallparadis geology, taphonomy and paleonvironment are also provided. PMID- 22078311 TI - The clinical effectiveness and cost-effectiveness of management strategies for sciatica: systematic review and economic model. PMID- 22078312 TI - Exact score distribution computation for ontological similarity searches. AB - BACKGROUND: Semantic similarity searches in ontologies are an important component of many bioinformatic algorithms, e.g., finding functionally related proteins with the Gene Ontology or phenotypically similar diseases with the Human Phenotype Ontology (HPO). We have recently shown that the performance of semantic similarity searches can be improved by ranking results according to the probability of obtaining a given score at random rather than by the scores themselves. However, to date, there are no algorithms for computing the exact distribution of semantic similarity scores, which is necessary for computing the exact P-value of a given score. RESULTS: In this paper we consider the exact computation of score distributions for similarity searches in ontologies, and introduce a simple null hypothesis which can be used to compute a P-value for the statistical significance of similarity scores. We concentrate on measures based on Resnik's definition of ontological similarity. A new algorithm is proposed that collapses subgraphs of the ontology graph and thereby allows fast score distribution computation. The new algorithm is several orders of magnitude faster than the naive approach, as we demonstrate by computing score distributions for similarity searches in the HPO. It is shown that exact P-value calculation improves clinical diagnosis using the HPO compared to approaches based on sampling. CONCLUSIONS: The new algorithm enables for the first time exact P-value calculation via exact score distribution computation for ontology similarity searches. The approach is applicable to any ontology for which the annotation propagation rule holds and can improve any bioinformatic method that makes only use of the raw similarity scores. The algorithm was implemented in Java, supports any ontology in OBO format, and is available for non-commercial and academic usage under: https://compbio.charite.de/svn/hpo/trunk/src/tools/significance/ PMID- 22078314 TI - Loss of air sacs improved hominin speech abilities. AB - In this paper, the acoustic-perceptual effects of air sacs are investigated. Using an adaptive hearing experiment, it is shown that air sacs reduce the perceptual effect of vowel-like articulations. Air sacs are a feature of the vocal tract of all great apes, except humans. Because the presence or absence of air sacs is correlated with the anatomy of the hyoid bone, a probable minimum and maximum date of the loss of air sacs can be estimated from fossil hyoid bones. Australopithecus afarensis still had air sacs about 3.3 Ma, while Homo heidelbergensis, some 600 000 years ago and Homo neandethalensis some 60 000 years ago, did no longer. The reduced distinctiveness of articulations produced with an air sac is in line with the hypothesis that air sacs were selected against because of the evolution of complex vocal communication. This relation between complex vocal communication and fossil evidence may help to get a firmer estimate of when speech first evolved. PMID- 22078313 TI - Reduction of post-surgical pericardial adhesions using a pig model. AB - BACKGROUND: Post-surgical pericardial adhesions pose an increased risk of complications during redo sternotomies. Adhesive tissue formation is a normal response to tissue injury and involves complex patho-physiological processes including the actions of prostaglandins to cause plasma leakage and fibrin formation. The purpose of this study was to assess the ability of two non steroidal anti-inflammatory agents (Indomethacin and Rofecoxib) and a barrier (Coseal, a polyethylene glycol) to limit adhesion formation following cardiac surgery in a pig model. METHODS: Forty-four piglets were allocated equally to four treatment groups: Group 1: Control, Group 2: intramuscular Indomethacin, Group 3: oral Rofecoxib and Group 4: Coseal sprayed on the heart. A full median sternotomy was performed on each animal and the heart exposed. Adhesions were induced by rubbing tissues with gauze, applying sutures and leaving blood in the pericardial sac before chest closure. Plasma inflammatory markers including prostaglandin E(2) and thromboxane B(2) were measured preoperatively and on Days 2, 5 and 10 after surgery. Eight animals from each group were slaughtered after 12 weeks and 3 after 25 weeks. Adhesions were assessed macroscopically and microscopically. RESULTS: Compared to the Control group, the extent of adhesions was significantly less in all other groups whilst adhesion density was least in the Indomethacin and Coseal groups. Indomethacin and less so Rofecoxib, inhibited the synthesis of prostaglandin E(2) and thromboxane B(2) but there were no significant changes in other inflammatory markers. CONCLUSIONS: We conclude that systemic Indomethacin, and locally applied Coseal are suitable methods to markedly reduce pericardial and retrosternal adhesions. PMID- 22078315 TI - An introduction to the special section on application of leading pretreatments to switchgrass by the Biomass Refining Consortium for Applied Fundamentals and Innovation (CAFI). PMID- 22078318 TI - Differential expression of FCRLA in naive and activated mouse B cells. AB - FCRLA is an intracellular B cell protein that belongs to the FcR-like family. Using newly generated FCRLA-specific antibodies, we studied the constitutive expression pattern of mouse FCRLA and monitored changes during an immune response and following in vitro B cell activation. All B cell subpopulations examined expressed FCRLA. However, the level of FCRLA expression is determined by the stage of B cell differentiation. Low expression of FCRLA is characteristic of naive follicular and marginal zone B cells. High expression was detected in a small fraction of activated B cells scattered along migratory pathways in the lymphoid tissues. FCRLA-bright cells could be subdivided into two subpopulations, with high and low/undetectable level of intracellular immunoglobulins, which phenotypically resemble either plasma or memory B cells. High expression of FCRLA in subset(s) of terminally differentiated B-cells suggests that, being an ER protein, FCRLA may participate in the regulation of immunoglobulin assembly and secretion. PMID- 22078316 TI - Papillomavirus E5: the smallest oncoprotein with many functions. AB - Papillomaviruses (PVs) are established agents of human and animal cancers. They infect cutaneous and mucous epithelia. High Risk (HR) Human PVs (HPVs) are consistently associated with cancer of the uterine cervix, but are also involved in the etiopathogenesis of other cancer types. The early oncoproteins of PVs: E5, E6 and E7 are known to contribute to tumour progression. While the oncogenic activities of E6 and E7 are well characterised, the role of E5 is still rather nebulous. The widespread causal association of PVs with cancer makes their study worthwhile not only in humans but also in animal model systems. The Bovine PV (BPV) system has been the most useful animal model in understanding the oncogenic potential of PVs due to the pivotal role of its E5 oncoprotein in cell transformation. This review will highlight the differences between HPV-16 E5 (16E5) and E5 from other PVs, primarily from BPV. It will discuss the targeting of E5 as a possible therapeutic agent. PMID- 22078319 TI - Overlapping and distinct roles of GRK5 in TLR2-, and TLR3-induced inflammatory response in vivo. AB - G-protein coupled receptor kinase-5 (GRK5) is a recently described NFkappaB regulator in TLR4 signaling pathway. To determine whether the role of GRK5 is MyD88- or TRIF-dependent, we injected wild type and GRK5 knockout mice with Pam3CSK4 (MyD88-dependent TLR1/2 ligand) and Poly(I:C) (TRIF-dependent TLR3 ligand) and examined the in vivo systemic inflammatory response. Our results demonstrate that GRK5 regulates IL-12p40 and G-CSF via a mechanism that is common to both MyD88 and TRIF. However, GRK5 regulates IL-5 and MCP-1 in a MyD88 dependent but TNFalpha in a TRIF-dependent manner. Together, our results demonstrate multiple roles of GRK5 in TLR signaling. PMID- 22078320 TI - Gender effect on in vitro lymphocyte subset levels of healthy individuals. AB - Differences in gender immune response have resulted in differences in immune protection and susceptibility to inflammatory diseases. Cultured peripheral blood mononuclear cells (PBMC) are widely used in immunomodulation studies, yet the influence of gender is usually not considered. We examined the effect of in vitro culture and phytohaemagglutinin (PHA) stimulation on PBMC lymphocyte subsets using flowcytometry. Full blood counts of whole blood showed higher levels of lymphocyte in male subjects. Lymphocyte subsets enumeration revealed higher NK cell counts in males and higher B cells in females. Cultured PBMC resulted in significant increases in B and total T cell percentages among females and NK cells among males. PHA stimulated significantly increased percentages of NK and total T cells in males and total activated T cells (CD69+) in females. Our results showed significant gender differences in lymphocyte subsets in cultured conditions. This may affect experimental outcome. PMID- 22078322 TI - A ten-year radiologic comparison of two-all polyethylene glenoid component designs: a prospective trial. AB - BACKGROUND: Aseptic glenoid component loosening remains a common problem in total shoulder arthroplasty (TSA). This study presents long-term prospective follow-up of 2 cemented all-polyethylene glenoid components with different backside design geometry and the effect on the presence and progression of radiolucent lines (RLLs). MATERIALS AND METHODS: Fifty-six TSAs were performed for primary osteoarthritis. Two surgeons used an identical technique to implant 32 flat-back and 24 convex-back glenoids. In particular, the glenoid components were cemented after a minimal reaming and bone compaction. Standardized postoperative radiologic and clinical follow-up was at 2 and 10 years. Three independent observers evaluated the x-ray images for RLLs around the base plate and keel. The results were analyzed for progression and influencing factors. RESULTS: At 10 years, progression of RLL was seen in both components, but there was no difference between the 2 glenoid designs (P = .16). Younger patient age (P = .03), hand dominance (P = .017), and presence of early RLLs (P = .018) were significant factors for progression of RLLs. Constant scores deteriorated with progression of RLLs (P = .006). The glenoid revision rate at 10 years was 5%. CONCLUSION: At 10 years there was no difference in the presence or progression of RRLs between a flat-back and a convex-back glenoid all-polyethylene design. Young age, hand dominance, and poor implantation technique influence glenoid RLLs and affect the clinical result of TSA. PMID- 22078323 TI - Implant sonication for the diagnosis of prosthetic elbow infection. AB - BACKGROUND: Periprosthetic infection is a potentially devastating complication of elbow arthroplasty, associated with formation of microbial biofilm on the implant surface. The definitive microbiologic diagnosis of periprosthetic infection after elbow arthroplasty may be difficult to establish. Our study aim was to compare the diagnostic accuracy of conventional periprosthetic tissue culture and culture of fluid derived from vortexing and bath sonication of the explanted hardware (a biofilm-sampling strategy). MATERIALS AND METHODS: Patients undergoing revision elbow arthroplasty at our institution between July 2007 and July 2010, from each of whom 2 or more periprosthetic tissue cultures and 1 implant sonicate culture were obtained, were studied. A standardized definition of orthopedic implant associated infection was applied. RESULTS: We identified 27 subjects with aseptic failure and 9 with prosthetic elbow infection. Rheumatoid arthritis was the most common underlying disorder. The Coonrad-Morrey prosthesis was the most common type of implant used. The sensitivities of implant sonicate and periprosthetic tissue culture were 89% and 55%, respectively (P = .18), and the specificities were 100% and 93%, respectively (P = .16). Coagulase-negative staphylococci (n = 7) and Staphylococcus aureus (n = 2) were isolated in cases of infection. CONCLUSION: Culture of the implant by sonication is at least as sensitive as periprosthetic tissue culture to detect prosthetic elbow infection. PMID- 22078324 TI - Treatment of proximal humeral dysplasia epiphysealis hemimelica with custom hemiarthroplasty: a case report. PMID- 22078325 TI - The emerging NDM carbapenemases. AB - Carbapenems were the last beta-lactams retaining near-universal anti-Gram negative activity, but carbapenemases are spreading, conferring resistance. New Delhi metallo-beta-lactamase (NDM) enzymes are the latest carbapenemases to be recognized and since 2008 have been reported worldwide, mostly in bacteria from patients epidemiologically linked to the Indian subcontinent, where they occur widely in hospital and community infections, and also in contaminated urban water. The main type is NDM-1, but minor variants occur. NDM enzymes are present largely in Enterobacteriaceae, but also in non-fermenters and Vibrionaceae. Dissemination predominantly involves transfer of the blaNDM-1 gene among promiscuous plasmids and clonal outbreaks. Bacteria with NDM-1 are typically resistant to nearly all antibiotics, and reliable detection and surveillance are crucial. PMID- 22078326 TI - Burn resuscitation. AB - Fluid resuscitation following burn injury must support organ perfusion with the least amount of fluid necessary and the least physiological cost. Under resuscitation may lead to organ failure and death. With adoption of weight and injury size-based formulas for resuscitation, multiple organ dysfunction and inadequate resuscitation have become uncommon. Instead, administration of fluid volumes well in excess of historic guidelines has been reported. A number of strategies including greater use of colloids and vasoactive drugs are now under investigation to optimize preservation of end organ function while avoiding complications which can include respiratory failure and compartment syndromes. Adjuncts to resuscitation, such as antioxidants, are also being investigated along with parameters beyond urine output and vital signs to identify endpoints of therapy. Here we briefly review the state-of-the-art and provide a sample of protocols now under investigation in North American burn centers. PMID- 22078327 TI - Role and expression of FRS2 and FRS3 in prostate cancer. AB - BACKGROUND: FGF receptor substrates (FRS2 and FRS3) are key adaptor proteins that mediate FGF-FGFR signalling in benign as well as malignant tissue. Here we investigated FRS2 and FRS3 as a means of disrupting global FGF signalling in prostate cancer. METHODS: FRS2 and FRS3 manipulation was investigated in vitro using over-expression, knockdown and functional assays. FRS2 and FRS3 expression was profiled in cell lines and clinical tumors of different grades. RESULTS: In a panel of cell lines we observed ubiquitous FRS2 and FRS3 transcript and protein expression in both benign and malignant cells. We next tested functional redundancy of FRS2 and FRS3 in prostate cancer cells. In DU145 cells, specific FRS2 suppression inhibited FGF induced signalling. This effect was not apparent in cells stably over-expressing FRS3. Indeed FRS3 over-expression resulted in enhanced proliferation (p = 0.005) compared to control cells. Given this functional redundancy, we tested the therapeutic principle of dual targeting of FRS2 and FRS3 in prostate cancer. Co-suppression of FRS2 and FRS3 significantly inhibited ERK activation with a concomitant reduction in cell proliferation (p < 0.05), migration and invasion (p < 0.05). Synchronous knockdown of FRS2 and FRS3 with exposure to cytotoxic irradiation resulted in a significant reduction in prostate cancer cell survival compared to irradiation alone (p < 0.05). Importantly, this synergistic effect was not observed in benign cells. Finally, we investigated expression of FRS2 and FRS3 transcript in a cohort of micro dissected tumors of different grades as well as by immunohistochemistry in clinical biopsies. Here, we did not observe any difference in expression between benign and malignant biopsies. CONCLUSIONS: These results suggest functional overlap of FRS2 and FRS3 in mediating mitogenic FGF signalling in the prostate. FRS2 and FRS3 are not over-expressed in tumours but targeted dual inhibition may selectively adversely affect malignant but not benign prostate cells. PMID- 22078328 TI - Assessment and analysis of non-point source nitrogen and phosphorus loads in the Three Gorges Reservoir Area of Hubei Province, China. AB - Eutrophication due to non-point source (NPS) of nitrogen (N) and phosphorus (P) has become a serious pollution problem in many Chinese rivers. In this paper, the export coefficient model (ECM) was used to assess the influence of NPS on N and P loading to the Three Gorges Reservoir Area (TGRA) of Hubei Province, People's Republic of China. Data from the main non-point sources were analyzed from 1995 to 2007, including rural domestic wastes, distributed livestock farms, fertilizers and soil erosion. Additionally, the potential N and P loading from NPS originated from a variety of sources were estimated and analyzed from 1995 to 2007, including runoff from rural domestic waste, livestock farms, land use, and atmospheric deposition, using the ECM. These gave the temporal distributions of the potential NPS loads within the reservoir area. The results indicated that the potential total nitrogen (TN) load was much higher than the potential total phosphorus (TP) load. The calculated TN load was 2.83*10(4) tonnes, while the TP load was 2.14*10(3) tonnes in 2007, with a ratio of TN/TP of 13.23. Record shows that "algae blooms" occurred 8 times in TGRA that year. Therefore, there may be a correlation between the eutrophication potential in the inlet water of TGRA and the TN/TP ratio of potential NPS loads. These findings demonstrate that the export coefficient model could provide a simple and reliable approach to evaluate the potential N and P loading to the Three Gorges Reservoir Area of Hubei Province in the People's Republic of China and may be useful for the planning and management of the local agricultural watersheds. PMID- 22078329 TI - Influence of urban shapes on environmental noise: a case study in Aracaju-Brazil. AB - This paper discusses the results of a study about the influence of urban shapes on environmental noise in the city of Aracaju (Brazil). The study, which involved in situ measurements and acoustic simulations using SoundPLAN software, began with an analysis of the current acoustic scenario, followed by the creation and simulation of hypothetical scenarios in as yet unoccupied sectors of the region under study. The acoustic modeling and simulations were based on measurements of equivalent-continuous sound pressure level, LAeq, and vehicle flow data, and on the region's geometrics. The results reveal that the physical characteristics of the urban shape, such as construction density, the existence of open spaces, and the shape and physical position of buildings exert a significant influence on environmental noise. PMID- 22078330 TI - Sediment-adsorbed total mercury flux through Yolo Bypass, the primary floodway and wetland in the Sacramento Valley, California. AB - The fate and transport of mercury are of critical concern in lowland floodplains and wetlands worldwide, especially those with a history of upstream mining that increases the mobility of both dissolved and sediment-bound Hg in watersheds. A mass budget of total mercury (THg) quantifies sources and storage for particular areas - knowledge that is required for understanding of management options in lowland floodplains. In order to assess contaminant risk in the largest flood control bypass, prime wetland, and restoration target in the Sacramento River basin, we estimated empirical relationships between THg, suspended sediment concentration (SSC), and streamflow (Q) for each of the major inputs and outputs using data from various publicly available sources. These relationships were improved by incorporating statistical representations of the dynamics of seasonal and intra-flood exhaustion (hysteresis) of sediment and mercury. Using continuous records of Q to estimate SSC suspended sediment flux and SSC to estimate THg flux, we computed the net transfer of sediment-adsorbed mercury through the Yolo Bypass over a decade, 1993-2003. Flood control weirs spilling Sacramento River floodwaters into the bypass deliver ~75% of the water and ~50% of the river's suspended sediment load, while one Coast Range tributary of the bypass, Cache Creek, contributes twice the THg load of the mainstem Sacramento. Although estimated sediment flux entering Yolo Bypass is balanced by efflux to the Sacramento/San Francisco Bay-Delta, there is much evidence of deposition and remobilization of sediment in Yolo Bypass during flooding. These factors point to the importance of the bypass as sedimentary reservoir and as an evolving substrate for biogeochemical processing of heavy metals. The estimates of mercury flux suggest net deposition of ~500 kg in the 24,000 ha floodway over a decade, dominated by two large floods, representing a storage reservoir for this important contaminant. PMID- 22078332 TI - Patient-reported outcomes in bladder pain syndrome: qui auget dolorem, auget et scientiam (as pain increases, so increases knowledge). PMID- 22078333 TI - Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer. AB - BACKGROUND: Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are possible candidates for radical prostatectomy (RP). New biomarkers would be welcome. OBJECTIVE: Test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivates, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology after RP. DESIGN, SETTING, AND PARTICIPANTS: An observational prospective study was performed in 350 consecutive men diagnosed with clinically localised PCa who underwent RP. MEASUREMENTS: We determined the predictive accuracy of serum total PSA (tPSA), free PSA (fPSA), fPSA-to-tPSA ratio (%fPSA), p2PSA, %p2PSA, and PHI. The primary end point was to determine the accuracy of these biomarkers in predicting the presence of pT3 disease, pathologic Gleason sum>=7, Gleason sum upgrading, and tumour volume<0.5 ml. INTERVENTION: Open retropubic and robot-assisted laparoscopic RP was performed. Pelvic lymphadenectomy was performed according to baseline oncologic parameters and the surgeon's judgement. RESULTS AND LIMITATIONS: The %p2PSA and PHI levels were significantly higher in patients with pT3 disease, pathologic Gleason sum>=7, and Gleason sum upgrading (all p values<0.001). Conversely, %p2PSA and PHI levels were significantly lower in patients with tumour volume<0.5 ml (p<0.001). By univariate analysis, both %p2PSA and PHI were accurate predictors of pT3 disease, pathologic Gleason sum>=7, Gleason sum upgrading, and tumour volume<0.5 ml. By multivariate analyses, the inclusion of both %p2PSA and PHI significantly increased the predictive accuracy of a base multivariate model (excluding the tumour volume prediction for both variables, and Gleason sum upgrading for the model including %p2PSA) that included patient age, tPSA, fPSA, f/tPSA, clinical stage, and biopsy Gleason sum. CONCLUSIONS: We found that p2PSA and its derivatives are predictors of PCa characteristics at final pathology after RP and are more accurate than currently available markers. PMID- 22078334 TI - Residual tumor size and IGCCCG risk classification predict additional vascular procedures in patients with germ cell tumors and residual tumor resection: a multicenter analysis of the German Testicular Cancer Study Group. AB - BACKGROUND: Residual tumor resection (RTR) after chemotherapy in patients with advanced germ cell tumors (GCT) is an important part of the multimodal treatment. To provide a complete resection of residual tumor, additional surgical procedures are sometimes necessary. In particular, additional vascular interventions are high-risk procedures that require multidisciplinary planning and adequate resources to optimize outcome. OBJECTIVES: The aim was to identify parameters that predict additional vascular procedures during RTR in GCT patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis was performed in 402 GCT patients who underwent 414 RTRs in 9 German Testicular Cancer Study Group (GTCSG) centers. Overall, 339 of 414 RTRs were evaluable with complete perioperative data sets. MEASUREMENTS: The RTR database was queried for additional vascular procedures (inferior vena cava [IVC] interventions, aortic prosthesis) and correlated to International Germ Cell Cancer Collaborative Group (IGCCCG) classification and residual tumor volume. RESULTS AND LIMITATIONS: In 40 RTRs, major vascular procedures (23 IVC resections with or without prosthesis, 11 partial IVC resections, and 6 aortic prostheses) were performed. In univariate analysis, the necessity of IVC intervention was significantly correlated with IGCCCG (14.1% intermediate/poor vs 4.8% good; p=0.0047) and residual tumor size (3.7% size < 5 cm vs 17.9% size >= 5 cm; p < 0.0001). In multivariate analysis, IVC intervention was significantly associated with residual tumor size >= 5 cm (odds ratio [OR]: 4.61; p=0.0007). In a predictive model combining residual tumor size and IGCCCG classification, every fifth patient (20.4%) with a residual tumor size >= 5 cm and intermediate or poor prognosis needed an IVC intervention during RTR. The need for an aortic prosthesis showed no correlation to either IGCCCG (p=0.1811) or tumor size (p=0.0651). CONCLUSIONS: The necessity for IVC intervention during RTR is correlated to residual tumor size and initial IGCCCG classification. Patients with high-volume residual tumors and intermediate or poor risk features must initially be identified as high-risk patients for vascular procedures and therefore should be referred to specialized surgical centers with the ad hoc possibility of vascular interventions. PMID- 22078335 TI - Re: Guillaume Ploussard, Alexandre de la Taille, Younes Bayoud, et al. The risk of upstaged disease increases with body mass index in low-risk prostate cancer patients eligible for active surveillance. Eur Urol 2012;61:356-62. PMID- 22078336 TI - How do you know if you are any good? A surgeon performance feedback system for the outcomes of radical prostatectomy. PMID- 22078337 TI - Prospective randomised controlled trial comparing trigone-sparing versus trigone including intradetrusor injection of abobotulinumtoxinA for refractory idiopathic detrusor overactivity. AB - BACKGROUND: Botulinum toxin A is effective for treatment of idiopathic detrusor overactivity (IDO). The trigone is generally spared because of the theoretical risk of vesicoureteric reflux (VUR), although studies assessing injection sites are lacking. OBJECTIVE: Evaluate efficacy and safety of trigone-including versus trigone-sparing intradetrusor injections of abobotulinumtoxinA in patients with IDO. DESIGN, SETTING, AND PARTICIPANTS: Twenty-two patients from one centre were randomised to trigone-including or trigone-sparing injections. INTERVENTION: Injection of 500 U abobotulinumtoxinA diluted to 20ml into 20 trigone-including or trigone-sparing sites. MEASUREMENTS: The primary outcome measure was total overactive bladder symptom score (OABSS) at 6 wk. The OABSS questionnaire was completed at 0, 6, 12, and 26 wk. Baseline and postinjection urodynamic studies and micturating cystourethrograms were performed. Baseline values and subsequent time points were compared by t test. A mixed-effect model was used for repeated measures in time. RESULTS AND LIMITATIONS: For symptom scores at baseline compared with scores at 6 wk postinjection, the mean total OABSS improved from 22.4 to 8.7 (p<0.001) in the trigone-including group compared with 22.7 to 13.4 (p<0.03) in the trigone-sparing group. The difference in mean change from baseline was 4.4 points in favour of the trigone-including group (p=0.03). The total OABSS at 12 and 26 wk and the urgency subscale scores at 6, 12, and 26 wk showed significant improvement in favour of the trigone-including group. Mean postvoid residual volumes and clean intermittent self-catheterisation rates between the two groups were similar. No patients developed VUR. Performing injections under general anaesthetic was a limitation, as tolerability under local anaesthetic was not assessed. A further limitation is the lack of a trigone only arm. CONCLUSIONS: Trigone-including injections are superior to trigone sparing injections for the treatment of refractory IDO and did not cause VUR in this study. PMID- 22078338 TI - Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. AB - BACKGROUND: Few predictive models aimed at predicting the presence of lymph node invasion (LNI) in patients with prostate cancer (PCa) treated with extended pelvic lymph node dissection (ePLND) are available to date. OBJECTIVE: Update a nomogram predicting the presence of LNI in patients treated with ePLND at the time of radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: The study included 588 patients with clinically localised PCa treated between September 2006 and October 2010 at a single tertiary referral centre. INTERVENTION: All patients underwent RP and ePLND invariably including removal of obturator, external iliac, and hypogastric nodes. MEASUREMENTS: Prostate-specific antigen, clinical stage, and primary and secondary biopsy Gleason grade as well as percentage of positive cores were included in univariable (UVA) and multivariable (MVA) logistic regression models predicting LNI and formed the basis for the regression coefficient-based nomogram. The area under the curve (AUC) method was used to quantify the predictive accuracy (PA) of the model. RESULTS AND LIMITATIONS: The mean number of lymph nodes removed and examined was 20.8 (median: 19; range: 10-52). LNI was found in 49 of 588 patients (8.3%). All preoperative PCa characteristics differed significantly between LNI-positive and LNI-negative patients (all p<0.001). In UVA predictive accuracy analyses, percentage of positive cores was the most accurate predictor of LNI (AUC: 79.5%). At MVA, clinical stage, primary biopsy Gleason grade, and percentage of positive cores were independent predictors of LNI (all p<=0.006). The updated nomogram demonstrated a bootstrap-corrected PA of 87.6%. Using a 5% nomogram cut-off, 385 of 588 patients (65.5%) would be spared ePLND. and LNI would be missed in only 6 patients (1.5%). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 87.8%, 70.3%, and 98.4%, respectively. The relatively low number of patients included as well as the lack of an external validation represent the main limitations of our study. CONCLUSIONS: We report the first update of a nomogram predicting the presence of LNI in patients treated with ePLND. The nomogram maintained high accuracy, even in more contemporary patients (87.6%). Because percentage of positive cores represents the foremost predictor of LNI, its inclusion should be mandatory in any LNI prediction model. Based on our model, those patients with a LNI risk<5% might be safely spared ePLND. PMID- 22078340 TI - Mesoporous hollow spheres from soap bubbling. AB - The smaller and more stable bubbles can be generated from the large parent bubbles by rupture. In the presence of a bubble blowing agent, hollow spheres can be prepared by bubbling a silica sol. Herein, the trapped gas inside the bubble acts as a template. When the porogen, i.e., other surfactant, is introduced, a mesostructured shell forms by the co-assembly with the silica sol during sol-gel process. Morphological evolution emphasizes the prerequisite of an intermediate interior gas flow rate and high exterior gas flow rate for hollow spheres. The method is valid for many compositions from inorganic, polymer to their composites. PMID- 22078339 TI - Ultrasound-assisted preparation and characterization of crystalline cellulose ionic liquid blend polymeric material: a prelude to the study of its application toward the effective adsorption of chromium. AB - The molecular interaction of biopolymers with an array of substrates offers interesting insight into the adsorption phenomenon. The present work proposes the preparation and characterization of cellulose-methyltrioctylammonium chloride (MeTOACl)-a room temperature ionic liquid (IL) blend polymeric sorbent and its application for the adsorption of carcinogenic chromium(VI). The blend adsorbent material was synthesized in a relatively green solvent (methylisobutylketone) medium by ultrasonication. The mechanism of interaction of biopolymer with the ionic liquid could be conceptualized as electrostatic attraction, hydrogen bonding, and Van der Waals force of attraction with the hydroxyl groups of cellulose as a bilayer assembly. The composition, crystallinity, and the surface area of the prepared material were comprehensively characterized using FT-IR, solid-state (13)C NMR, TGA, XRD, SEM, EDX, XPS, and BET isotherm study. The adsorption capacity of chromium(VI) calculated from Langmuir isotherm model was found to be 38.94 mg g(-1) with adherence to the second-order kinetics. The study of thermodynamic parameters that affect the sorption process indicated the spontaneity and exothermic nature of adsorption. The green aspect in the methodology is brought out in the regeneration of the adsorbent, where Cr(VI) could be effectively reduced to the less toxic Cr(III) using ascorbic acid. PMID- 22078341 TI - Advances in information and communication technology (ICT): issues, challenges and opportunities for health care professionals. PMID- 22078342 TI - Thoracic epidural anaesthesia for open cholecystectomy. AB - OBJECTIVE: To compare the postoperative pain relief and vomiting and the length of hospital stay in patients undergoing open cholecystectomy under general anaesthesia versus those receiving thoracic epidural anaesthesia. STUDY DESIGN: Quasi experimental study. PLACE AND DURATION OF STUDY: The Combined Military Hospital, Skardu, from February 2009 to July 2010. METHODOLOGY: American Society of Anaesthesiology (ASA) physical status (PS) I and II patients of either gender undergoing un-complicated open cholecystectomy were randomly divided into two groups, group 1 (n=51) received general anaesthesia (GA) and group 2 (n=49) received thoracic epidural anaesthesia (EA). Patients of both the groups were assessed for postoperative pain, vomiting and length of hospital stay. Chi-square test was applied to compare the two groups and obtain the p-value. P-value of less than 0.05 was considered significant. RESULTS: Thirty six patients of GA group did not require additional analgesics for postoperative pain relief; however, injection Ketorolac had to be administered to 15 patients (29.4%) for pain relief in the postoperative period. Two patients (4.1%) in the EA group required additional analgesic during that period. Eleven patients (21.5%) in the GA group had postoperative vomiting. In the EA group only 1 patient (2%) had postoperative vomiting. Patients in EA group had better postoperative pain relief (p = 0.001) and remained free from vomiting than the GA group (p = 0.003). Thirty six patients (70.5%) of the GA group and 34 patients (69.4%) in the EA group were discharged within 36 hours postoperatively (p = 0.896). CONCLUSION: The use of intra-operative epidural anaesthesia combined with postoperative epidural analgesia was found to be associated with reduction in the postoperative pain and vomiting in patients undergoing open cholecystectomy. PMID- 22078343 TI - Personal and social factors regarding medical non-compliance in cardiac failure patients. AB - OBJECTIVE: To determine the frequency and association of various personal and social factors with medical non-compliance in cardiac failure patients. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: National Institute of Cardiovascular Diseases (NICVD), Karachi from January to August 2010. METHODOLOGY: Patients admitted in the medical wards of NICVD, who were being treated for cardiac failure, were included. Information regarding basic demographics, education level, self engagement in therapy and status of compliance was obtained by questionnaire. Statistical analysis was carried out by using Fisher's exact test and chi-square. Level of significance was < 0.05. Data was analyzed using SPSS V-15. RESULTS: Out of 267 patients, 73 (27.3%) were compliant while 194 (72.7%) were non-compliant. Educated, self caring patient, and those who knew names of their medications were more compliant than the rest. CONCLUSION: Medical non-compliance is very common in heart failure patients. Illiteracy and no self engagement in therapy are associated with non-compliance. PMID- 22078344 TI - Factors associated with tobacco smoking among 6-10 grade school students in an urban Taluka of Sindh. AB - OBJECTIVE: To determine the factors related to tobacco smoking among students of grade 6-10 in an urban setting in Sindh, Pakistan. STUDY DESIGN: Cross-sectional survey. PLACE AND DURATION OF STUDY: The study was conducted in public and private schools of Hyderabad, Sindh, Pakistan, from January 2008 to June 2009. METHODOLOGY: A sample of 501 students from grade 6-10 were selected through simple random sampling and probability proportional to size. Students answered to a pre-tested questionnaire on sociodemography and tobacco use. Descriptive statistics were used to determine frequency distribution. RESULTS: About 9% of the students were smoking some form of tobacco. Ten percent had tried cigarette smoking and about 80% and 61% were chewing Areca nuts and 'Paan' (concoction of Areca nuts, tobacco, hydrated lime, herbs and spices wrapped in betel leaf. Being old, male gender, peer influence, personal attitude toward future smoking, chewing 'Gutka' (concoction of tobacco, Areca nuts and hydrated lime) and having a more educated mother was associated with greater frequency of smoking any form of tobacco. CONCLUSION: High frequency of tobacco smoking, the attitude toward tobacco consumption and a very high consumption of Areca nuts and other chewable tobacco products by the children warrants urgent action in order to control the tobacco epidemic in Pakistan. PMID- 22078345 TI - Efficacy of L-ornithine-L-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy. AB - OBJECTIVE: To evaluate the efficacy of L-ornithine-L-aspartate (LOLA) as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy (HE). STUDY DESIGN: Randomized placebo controlled study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi in the year 2003-2004. METHODOLOGY: Patients with HE were randomized to receive LOLA or placebo medicine as an adjuvant to treatment of HE. Number connection test-A (NCT-A), ammonia level, clinical grade of HE and duration of hospitalization were assessed. RESULTS: Out of 120 patients, there were 62 males with mean age of 57 +/- 11 years. Improvement in HE was higher (n=40, 66.7%) in LOLA group as compared to the placebo group (n=28, 46.7%, p=0.027). In patients with grade I or less encephalopathy, improvement was seen in 6 (35.3%) and 3 (20%) patients in LOLA and placebo groups respectively (p=0.667). Patients with HE grade II and above showed improvement in 34 (79.1%) and 25 (55.6%) cases in LOLA and placebo group respectively (p=0.019). On multivariate analysis patients with HE of grade II and above showed prothrombin time, creatinine level and use of LOLA influencing the outcome. Duration of hospitalization was 93.6 +/- 25.7 hours and 135.2 +/- 103.5 hours in LOLA and placebo groups respectively (p=0.025). No side effects were observed in either groups. CONCLUSION: In cirrhotic patients with advanced hepatic encephalopathy treatment with LOLA was safe and associated with relatively rapid improvement and shorter hospital stay. PMID- 22078346 TI - Surgical management of femoral artery pseudoaneurysms secondary to drug abuse. AB - OBJECTIVE: To assess the outcome of surgical management of mycotic false aneurysms due to local injury after intravenous injection of drugs. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Surgery, Kerman Medical School of Sciences, Kerman, Iran, from July 2001 to June 2009. METHODOLOGY: Twenty one consecutive patients presenting with infected femoral artery pseudoaneurysms (IFAPs) secondary to parenteral drug abuse treated in our department were studied. Data analyzed included demographic characteristics, modes of presentation, side of involvement, management and outcome. RESULTS: All patients were male with mean age of 32.2 +/- 5.2 years. All presented with pain and swelling in the groin. Five patients presented with significant hemorrhage. The locations were the left side in 9 cases and the right side in 12 cases. The injured artery was the common femoral artery and its bifurcation. In 14 patients (64%), ligation-excision was carried out. In 5 patients (26%), primary repair of the artery with over-sewing was done. In 2 patients (10%), revascularization with saphenous interposition was carried out. Below-knee amputation was necessary in 1 patient who underwent ligationexcision. One patient died due to severe septicemia. CONCLUSION: Ligation of IFAPs is an effective, safe and simple option. Primary repair with preservation of the native vessel is suggested if infection is limited. PMID- 22078347 TI - Ocular digital massage for the management of post- trabeculectomy underfiltering blebs. AB - OBJECTIVE: To evaluate the efficacy and safety of ocular digital massage (ODM) in the management of underfiltering blebs after trabeculectomy. STUDY DESIGN: Quasi experimental study. PLACE AND DURATION OF STUDY: Glaucoma Clinic of Al-Shifa Trust Eye Hospital, Rawalpindi, from January 2007 to November 2008. METHODOLOGY: ODM was performed 3-4 times daily in 20 eyes having intraocular pressure (IOP) above the target level after trabeculectomy. Equal number of eyes with satisfactory IOP after trabeculectomy were taken as controls. Both groups were evaluated at 1 week, 3 weeks, 6 weeks, 3 months, 6 months and 9 months. Mean IOP, frequency of complications and required number of IOP lowering medicines in both groups were compared using 't' test. RESULTS: Massage group had a significantly higher mean IOP than the control group before the initiation of massage (p < 0.001). After initiating ODM, there were no significant differences in the mean IOP of two groups at 1 week (p = 0.421), 3 weeks (p = 0.073), 6 weeks (p = 0.575), 3 months (p = 0.071), 6 months (p = 0.085) and 9 months (p = 0.369). The difference in terms of required number of IOP lowering medicines (p = 0.075) and complication rates (p = 0.411) was also not significant. CONCLUSION: ODM is an effective method for controlling IOP after trabeculectomy, and thus contributes to long-term surgical success with an acceptable risk / benefit ratio. PMID- 22078348 TI - BRCA1 status in Pakistani breast cancer patients with moderate family history. AB - OBJECTIVE: To determine BRCA1 status in breast carcinoma patients of Pakistani origin. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: The Oncology Clinics of the Aga Khan University Hospital, Karachi, between May 2005 and December 2009. METHODOLOGY: Fifty three breast cancer patients based on clinical and laboratory diagnosis were recruited for this study. Moderate family history was defined as having a close relative (mother, daughter, sister) diagnosed with breast cancer under 45 years. Peripheral blood samples were collected from each patient in a 5 ml tube containing EDTA as anticoagulant. Subsequent to DNA extraction, mutational analysis of BRCA1 exons 2, 5, 6, 16, 20 and 22 was carried out using single strand conformation polymorphism (SSCP) assay while protein truncation test (PTT) was used to examine mutations in exon 11. All BRCA1 sequence variants were confirmed by DNA sequencing. RESULTS: Twenty-three patients were diagnosed with early onset breast cancer, 30 patients had moderate family history. At the time of diagnosis, the median age of enrolled patients was 39 years (range 24-65 years). Out of 53 patients, analyzed by SSCP assay, mobility shift was detected in exon 6, 16 and 20 of three patients, whereas one patient was tested positive for mutation in exon 11 by PTT assays. All patients with BRCA1 mutations were further confirmed by DNA sequencing analysis. In exon 16 c.4837A > G was confirmed, which is a common polymorphism reported in several populations including Asians. Moreover, mutations in exon 6 (c.271T > G), exon 20 (c.5231 delG) and exon 11 (c.1123 T > G) were reported first time in the Pakistani population. CONCLUSION: Several BRCA1 mutations were observed in Pakistani breast cancer patients with moderate family history. Therefore, mutation-based genetic counselling for patients with moderate family history can facilitate management, if one first or second degree relative or early onset disease is apparent. PMID- 22078349 TI - Clinical applicability of variations in arch dimensions and arch forms among various vertical facial patterns. AB - OBJECTIVE: To compare dental arch dimensions and arch forms in various vertical facial patterns. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from June 2007 to May 2008. METHODOLOGY: Cases of age ranging 13-30 years were reviewed having full complement of teeth (upto second permanent molars) with less than 7 mm crowding. Exclusion criteria included presence of dental anomalies, previous dentoalveolar surgery, trauma or orthodontic treatment and craniofacial syndromes. One hundred cases including 40 normodivergent, 30 hypodivergent and 30 hyperdivergent facial patterns were selected. Occlusograms were made and various arch dimensions were measured. Arch forms were calculated according to ratios of three sagittal to three transverse dimensions. RESULTS: The mean age of the sample was 21 years and 5 months. Significant differences in arch dimensions were found only in maxillary total arch length (p=0.03) and mandibular posterior intermolar width (p=0.04). Wide lower arches were predominant in all face types. Wide upper arches were predominant only in hypo- and hyperdivergent subjects. CONCLUSION: Statistically significant difference in arch dimensions was found only in maxillary total arch length and mandibular posterior intermolar width. A non-linear relationship was found between arch length and arch width. Wide lower arches were predominant in all face types whereas wide upper arches were predominant in hypo- and hyperdivergent subjects. PMID- 22078350 TI - The burnt child: an epidemiological profile and outcome. AB - OBJECTIVE: To determine the epidemiologic pattern and outcome of childhood burns by finding the presenting features of the burn victims, causes / circumstances of burn injury, involvement of body area, need for hospitalization, duration of hospital stay and mortality. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: The Burns Care Centre (BCC), Pakistan Institute of Medical Sciences (PIMS), Islamabad, from January 2008 to June 2010. METHODOLOGY: All children of either gender with burn injuries who were managed at the centre after primarily presenting to the study centre were included. Children over 15 years were excluded. Lund and Browder chart was used to calculate the total body surface area (TBSA) burnt. Children with extensive and critical burns, high voltage electric burns and those needing any surgical interventions were admitted for indoor management. Data were recorded on a proforma. RESULTS: A total of 1725 children were included in the study. Out of those, 66.84% (n=1153) were males and 33.15% (n=572) were females. The mean age was 5.04 +/- 2.78 years. Majority (67.47%) of children were aged 3-6 years. Scalds were the commonest burns (70.31%). Household environment was the commonest site of acquisition of burns (91.47%). Winter was the most frequent season of sustaining burn injury (63%). The commonest anatomic regions affected were hands / upper limbs (65.68%). Overall the affected mean TBSA was 9.37 +/- 9.61 %, while for the hospitalized children it was 27.07 +/- 10.84%. Two hundred and ninety seven children (17.21%) were admitted. The mean hospital stay was 15.59 +/- 5.61 days. The mortality rate was 9.09% for the hospitalized children and 1.56% for the entire study sample. CONCLUSION: Male gender, age of 3-6 years and winter season were found to have an increased frequency of childhood burns. Scalds were the commonest type of injuries, and hands/ upper limbs were the most frequently affected body parts. There is a need to revisit the health care system and institute focused burn prevention strategies consistent with our local circumstances. PMID- 22078351 TI - Mortality in meconium aspiration syndrome in hospitalized babies. AB - OBJECTIVE: To determine the outcome of the babies in terms of mortality with the diagnosis of Meconium Aspiration Syndrome (MAS). STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: The Neonatal Unit of Services Institute of Medical Sciences and Services Hospital, Lahore, Pakistan, from February 2008 to January 2009. METHODOLOGY: All the babies admitted to the neonatal unit during the period of study with the diagnosis of MAS were included. At admission, demographic, maternal, antenatal and natal data were recorded on a specific form. The progress of the baby, including need for ventilation, medications, complications and outcome were also followed and documented. RESULTS: One hundred and nine babies admitted with MAS, 32% died. Most of the babies (n=73) were admitted from our obstetrical unit and the rest through the emergency department. Majority (60 of 109) were admitted within the 1st hour of life. Most (14 of 15) of the newborns requiring intubation within 1st hour of life, died. Forty four babies were ventilated and 35 of these babies succumbed. Of ventilated babies, 11 developed pneumothoraces. Seventy two percent (13 out of 18) of expired babies stayed for less than 24 hours. CONCLUSION: Mortality rate for MAS was higher in the study group as compared to international figures. It was especially high in babies requiring mechanical ventilation in 1st hour of life or with co-existing severe hypoxic ischemic encephalopathy. PMID- 22078352 TI - Right sided single coronary artery origin: surgical interventions without clinical consequences. AB - Congenital coronary anomalies are uncommon and are usually diagnosed incidentally during coronary angiogram or autopsy. Isolated coronary artery anomalies and the anomalous origin of left main stem (LMS) from the proximal portion of the right coronary artery or from the right sinus of valsalva are extremely rare. A 68 years old woman with atypical chest pains was referred for risk assessment for the general anaesthesia. A stress exercise treadmill test and myocardial perfusion scan revealed evidence of mild myocardial ischemia. Her coronary angiography revealed her left coronary artery to have a single origin with the right coronary artery. There were no flowlimiting lesions. A CT aortography confirmed a retro-aortic course of the left coronary artery. She successfully underwent multiple surgical procedures under general anaesthesia including total abdominal hysterectomy, Burch colposuspension (twice) for stress incontinence, intravesical botox injection for urge incontinence and haemorrhoidectomy for recurrent rectal mucosal prolapse. Various anaesthetic agents including halothane, thiopentone, suxamethonium, pancuronium, enflurane, fentanyl, propofol and isoflurane were used without any adverse clinical consequences. She remained well on 48 months follow-up. PMID- 22078353 TI - Paraurethral leiomyoma. AB - Vaginal leiomyoma is a rare solid tumour with a variable presentation that can lead to pre-operative misdiagnosis. Local recurrence and transformation into sarcoma are also rare and surgical excision is recommended. Here, we present the case of a 23-year-old woman with a painless vaginal mass associated with severe dyspareunia since marriage (2 months ago) and dysmenorrhoea. She underwent surgery by vaginal route and histological findings confirmed a leiomyoma. After 2 months, the patient was disease-free and symptoms disappeared. PMID- 22078354 TI - Lingual tuberculosis. AB - Tuberculosis is a common disease in developing countries like Pakistan. Although it can involve almost any region of the body, some presentations are still very rare. This is a case report of a 36 years old male with tuberculous lesion on the tongue presenting as a lump. Patient also had disseminated disease. There are very few cases reported of this rare presentation across the globe. PMID- 22078355 TI - Amyloidosis of the nasopharynx: an unexpected cause of unilateral middle ear effusion. AB - Amyloidosis is an idiopathic disease that is characterized by the extracellular deposition of fibrillar proteins. The disease can be categorized as primary or secondary where deposits occur in conjunction with chronic diseases such as rheumatoid arthritis or tuberculosis. The deposits can be localized or systemically distributed. It can mimic, and also be associated with underlying malignancy. Primary amyloidosis is a rare cause of a nasopharyngeal lesion, and less so of a secondary middle ear effusion. Its association with underlying chronic and malignant disease must not be over-looked if serious complications are to be avoided. It is, therefore, important to consider this as a differential diagnosis in such patients. PMID- 22078356 TI - Digital gangrene in end-stage renal disease. AB - Ischemic complications presenting as digital gangrene occurring in a patient of end-stage renal disease undergoing haemodialysis is rarely reported in literature. We report one such case of dry gangrene of a single finger in a 53 years old male undergoing haemodialysis. The condition was likely a steal phenomenon secondary to the surgical angioaccess for dialysis. PMID- 22078357 TI - Zygodactyly with thumb aplasia: an unusual variant in a male subject. AB - This is a presentation of a male subject with unusual combination of limb malformations. The subject had unilateral zygodactyly of the left foot with thumb aplasia in the right hand. Further, the webbing between second and third toes was complete culminating in osseous fusion of the terminal phalanges and valgus deviation of the affected digits of the foot. The nails were also involved but had separate origins. In the right hand, first digital ray was observed to be completely omitted. There was aplasia of certain carpals while the radius showed minimal clinical symptoms. The subject was the product of first cousins union. To the best of our knowledge, this combination of limb phenotype has not been described before. PMID- 22078358 TI - Primary renal leiomyosarcoma. AB - Primary renal sarcomas are very rare. We report a case of renal leiomyosarcoma with 36 months follow-up. Neither ultrasonography, computed tomography nor magnetic resonance imaging are able to differentiate between leiomyosarcoma and renal cell carcinoma. Radical nephrectomy and adrenalectomy was curative. Diagnosis was established on histology and immunohistochemistry. There were no metastases. Histology and later on immunohistochemistry is the only mean by which these tumours can be diagnosed. After a period of 36 months, patient is alive and well. PMID- 22078359 TI - Demographic and clinical profile of children under two years of age with recurrent wheezing. AB - Sixty-seven children less than two years of age with recurrent wheezing were evaluated clinically and demographically by proper history and clinical examinations. The mean age of the study subjects at enrolment and at onset of wheezing was 10.8 + 5.24 months and 7.1 + 3.857 months, respectively. The male female ratio was 9:2. The majority of these cases (82%) had onset of wheezing at less than 1 year of age. One-third of the cases were diagnosed as asthma and viral infection associated wheeze. Increasing age in the first 2 years of life was significantly associated with decreasing trend of cases with history suggestive of reflux. The children with wheeze due to causes other than gastroesophageal reflux were more likely to be not exclusively breast fed. The present study did not find any significant difference in the prevalence of various socioeconomic, environmental factors and clinical factors among the various types of the early wheezers. PMID- 22078360 TI - Deferasirox induced liver injury in haemochromatosis. PMID- 22078361 TI - Iatrogenic severe protein deficiency in a child. PMID- 22078363 TI - Meta-analytic approach to the accurate prediction of secreted virulence effectors in gram-negative bacteria. AB - BACKGROUND: Many pathogens use a type III secretion system to translocate virulence proteins (called effectors) in order to adapt to the host environment. To date, many prediction tools for effector identification have been developed. However, these tools are insufficiently accurate for producing a list of putative effectors that can be applied directly for labor-intensive experimental verification. This also suggests that important features of effectors have yet to be fully characterized. RESULTS: In this study, we have constructed an accurate approach to predicting secreted virulence effectors from Gram-negative bacteria. This consists of a support vector machine-based discriminant analysis followed by a simple criteria-based filtering. The accuracy was assessed by estimating the average number of true positives in the top-20 ranking in the genome-wide screening. In the validation, 10 sets of 20 training and 20 testing examples were randomly selected from 40 known effectors of Salmonella enterica serovar Typhimurium LT2. On average, the SVM portion of our system predicted 9.7 true positives from 20 testing examples in the top-20 of the prediction. Removal of the N-terminal instability, codon adaptation index and ProtParam indices decreased the score to 7.6, 8.9 and 7.9, respectively. These discrimination features suggested that the following characteristics of effectors had been uncovered: unstable N-terminus, non-optimal codon usage, hydrophilic, and less aliphathic. The secondary filtering process represented by coexpression analysis and domain distribution analysis further refined the average true positive counts to 12.3. We further confirmed that our system can correctly predict known effectors of P. syringae DC3000, strongly indicating its feasibility. CONCLUSIONS: We have successfully developed an accurate prediction system for screening effectors on a genome-wide scale. We confirmed the accuracy of our system by external validation using known effectors of Salmonella and obtained the accurate list of putative effectors of the organism. The level of accuracy was sufficient to yield candidates for gene-directed experimental verification. Furthermore, new features of effectors were revealed: non-optimal codon usage and instability of the N-terminal region. From these findings, a new working hypothesis is proposed regarding mechanisms controlling the translocation of virulence effectors and determining the substrate specificity encoded in the secretion system. PMID- 22078364 TI - The smallest insects evolve anucleate neurons. AB - The smallest insects are comparable in size to unicellular organisms. Thus, their size affects their structure not only at the organ level, but also at the cellular level. Here we report the first finding of animals with an almost entirely anucleate nervous system. Adults of the smallest flying insects of the parasitic wasp genus Megaphragma (Hymenoptera: Trichogrammatidae) have only 339 372 nuclei in the central nervous system, i.e., their ganglia, including the brain, consist almost exclusively of processes of neurons. In contrast, their pupae have ganglia more typical of other insects, with about 7400 nuclei in the central nervous system. During the final phases of pupal development, most neuronal cell bodies lyse. As adults, these insects have many fewer nucleated neurons, a small number of cell bodies in different stages of lysis, and about 7000 anucleate cells. Although most neurons lack nuclei, these insects exhibit many important behaviors, including flight and searching for hosts. PMID- 22078365 TI - Self-reported tobacco smoke exposure and plasma cotinine levels during pregnancy- a validation study in Northern Japan. AB - Maternal smoking is a critical public health concern requiring the establishment of its prevalence rate and clinical impact. Maternal self-reported information of tobacco smoke exposure requires validation using accurate biochemical analysis. This study examined the association between self-reported exposure to tobacco smoke and plasma cotinine level in Japanese pregnant women. We collected information about smoking and secondhand smoke (SHS) exposure during pregnancy from 5128 pregnant women in a prospective cohort design, and analyzed biochemically maternal blood samples using the enzyme-linked immunosorbent assay (ELISA) technique. Based on self-reports, the subjects were classified into three groups: 650 smokers, 728 ex-smokers and 3750 non-smokers. Using the receiver operating characteristic (ROC) curve, plasma cotinine cut-off value of 11.48 ng/mL was established for separating smokers from non-smokers, resulting in a smoking prevalence of 14%. A cotinine cut-off value of 0.21 ng/mL for discriminating exposed and unexposed nonsmokers resulted in a 63% prevalence of exposure to tobacco smoke among nonsmokers. Cotinine biomarker analysis proved accurate in validating self-reported smoking information in the subjects. Lower validity of SHS exposure suggests a need to confirm questionnaire information with biochemical analysis. PMID- 22078366 TI - Three decades of atmospheric metal deposition in Norway as evident from analysis of moss samples. AB - Monitoring of atmospheric deposition of metals in Norway on a nationwide scale using samples of terrestrial moss started in 1977 and has been repeated every 5 years. This has facilitated a detailed record of temporal and spatial trends of metal deposition all over the country as a supplement to measurements based on bulk deposition sampling on a small number of sites. Pb, Zn, Cd, As, Sb, V, Sn, Mo, and Bi all show highest deposition in the far south due to trans-boundary pollution from other parts of Europe, but the contribution from long-range atmospheric transport to metal deposition has decreased substantially over the years. The distributions of Fe, Ni, Cu, Cr, and Co are more affected by local sources, but a decreasing time trend is also evident for these elements. Se is mainly derived from processes in the marine environment. Deposition of metals from Cu-Ni smelters in Russia situated close to the Norwegian border has shown a steadily increasing trend over the time period concerned. PMID- 22078367 TI - Inclusion of soil arsenic bioaccessibility in ecological risk assessment and comparison with biological effects. AB - The purpose of this study was to conduct an ecological risk assessment (ERA) for meadow voles (Microtus pennslvanicus) found at three arsenic contaminated sites in Nova Scotia, Canada (as well as two background locations) and to compare the numeric results to measured biomarkers of exposure and effect. The daily intake of arsenic by meadow voles was determined by three separate calculations: estimated daily intake (EDI), bioaccessible estimated daily intake (BEDI, with bioaccessibility of soil included), and actual daily intake (ADI, which is calculated with arsenic concentrations in the stomach contents). The median bioaccessibility of arsenic in soils from the contaminated locations was significantly greater than at background locations. The bioaccessible arsenic concentration in soil from all samples (both contaminated and background) was significantly less than the total concentration. Use of site-specific bioaccessibility (hazard quotients=38 at Upper Seal Harbour (USH); 60 at Lower Seal Harbour (LSH); and 120 at Montague tailings (MONT)) and stomach arsenic contents (hazard quotients=2.1 at USH; 7.9 at LSH; and 6.7 at MONT) in the ERA resulted in lower numeric risk than compared to risk calculated with 100% bioavailability (hazard quotient=180 at USH; 75 at LSH; and 680 at MONT). Further, the use of bioaccessibility on the calculation of risk was aligned with biomarker results (changes in glutathione and micronucleated erythrocytes) in voles captured at the sites. This study provides evidence that using site specific bioaccessibility in ERAs may provide a more realistic level of conservatism, thereby enhancing the accuracy of predicting risk to wildlife receptors. Furthermore, when numeric risk assessments are combined with site specific biological data (i.e., biomarkers of exposure and effect), both lines of evidence can be used to make informed decisions about ecological risk and site management. PMID- 22078368 TI - A systematic examination of a random sampling strategy for source apportionment calculations. AB - Estimating the relative contributions from multiple potential sources of a specific component in a mixed environmental matrix is a general challenge in diverse fields such as atmospheric, environmental and earth sciences. Perhaps the most common strategy for tackling such problems is by setting up a system of linear equations for the fractional influence of different sources. Even though an algebraic solution of this approach is possible for the common situation with N+1 sources and N source markers, such methodology introduces a bias, since it is implicitly assumed that the calculated fractions and the corresponding uncertainties are independent of the variability of the source distributions. Here, a random sampling (RS) strategy for accounting for such statistical bias is examined by investigating rationally designed synthetic data sets. This random sampling methodology is found to be robust and accurate with respect to reproducibility and predictability. This method is also compared to a numerical integration solution for a two-source situation where source variability also is included. A general observation from this examination is that the variability of the source profiles not only affects the calculated precision but also the mean/median source contributions. PMID- 22078369 TI - Possible social relevance of illicit psychotropic substances present in the atmosphere. AB - Although the worldwide presence of illicit psychotropic compounds in the environment is well known, the social impact of drug abuse on the community has yet to be determined. Besides, the possibility of deriving indicators of the prevalence of drug abuse from the content of illicit substances in the air remains unexplored. In this study, the atmospheric concentrations of psychotropic compounds recorded in Italy were plotted vs. a series of criminal statistics. Meaningful links were found between atmospheric cocaine and the amount of drugs seized, the number of drug related crimes and the demand for clinical treatment recorded in the Italian regions. Atmospheric cocaine and cannabinoids also seemed to be correlated with tumour insurgence and mental disease frequency, respectively. However, further investigations are necessary to elucidate/explain/clarify if the behaviours observed for cocaine vs. the parameters usually adopted to estimate drug abuse prevalence (correspond to an effective relationships)/are directly linked, and to understand why the same approach failed when applied to cannabinoids. Moreover, according to our study illicit drugs are suspected to promote long-term ill health effects even when present at low concentrations the air. PMID- 22078370 TI - Land-ocean contributions of arsenic through a river-estuary-ria system (SW Europe) under the influence of arsenopyrite deposits in the fluvial basin. AB - Water was sampled monthly from September 2005 to August 2006 at 14 stations distributed throughout the coastal system of Anllons-Laxe, from where 30 surface sediment samples were also taken. After filtration through 0.22 MUm polycarbonate filters, dissolved inorganic and total arsenic (UV oxidation) concentration was determined by HG-AFS. After microwave digestion, the arsenic in SPM and sediment was determined by AAS. Ultra-clean procedures were adopted during sampling, handling and analysis and the analytical accuracy was checked using certified reference material. Spatial distribution of As in water (0.2-4.0 MUg L(-1)), SPM (21-169 mg kg(-1)) and sediment of the river reservoir was altered by the presence of arsenopyrite deposits in the middle fluvial basin that increases 2.1+/-0.5 and 1.7+/-0.5 times the concentrations of inorganic dissolved (DI-As) and particulate (P-As) arsenic, respectively. At the termination fluvial zone As fluxes can be calculated to be: [DI-As]=7.09.Q(-0.69). The Anllons River exports to its estuary 460 kg a(-1) of dissolved (<7% as organic) arsenic annually. It is higher (i.e. 0.83 kgs(-1) km(-2) of DI-As) than that of most of European rivers. In the estuary reservoir, the influence of arsenopyrite is also evident as the river concentration of DI-As, which was lower than in seawater during the wet season and higher during the dry season. Arsenic has non-conservative behaviour, as in other European estuaries, but the Anllons shows an ambivalent pattern: as it usually gains DI-As during the wet season and loses it during the dry season, whilst P-As seems to behave contrary to the DI-As. When the fluvial arsenic reaches the ria its concentration varies due to the estuarine processes. In the wet season DI-As increases its concentration by one third whilst in the dry season it decreases by one fifth and the annual contribution to the ria is 10% higher than the fluvial output. In the case of P-As more data are necessary to quantify its behaviour; however, the estuarine sediments are contaminated by arsenic. In the ria reservoir DI-As levels were similar to those of the ocean, DO As comprises 9-22% of the inorganic, P-As ranges from 3 to 40 mg kg(-1), and As sedimentary can be classified as uncontaminated (4-18 mg kg(-1)), except in the fishing ports. The ria circulation, reinforced by upwelling favours the exportation of arsenic to the ocean. In the Anllons-Laxe system as a whole, the freshwater-saline interface processes do not lead to a decrease in the dissolved fluvial arsenic flux to the ocean. PMID- 22078371 TI - Arsenic in Chinese coals: distribution, modes of occurrence, and environmental effects. AB - Arsenic, one of the most hazardous elements occurring in coals, can be released to the environment during coal processing and combustion. Based on the available literature and published results obtained in our laboratory, the content, distribution and the modes of occurrence of As in Chinese coals, and its environmental and impacts are reviewed in this article. With the 4763 sets of data (from the literature) rearranged, the arithmetic mean As concentration of each province and weighted mean As concentration of the entire country (using the expected coal reserves as the weighting factor) were calculated. The weighted mean As concentration in Chinese coals is 3.18 mg/kg, with As concentration increasing from northern China to southern China. The As concentration in coal varies with coal-forming ages and coal ranks. Arsenic has several modes of occurrence in coals. According to results obtained by other studies and our own experiments, As is mainly associated with mineral matter (such as pyrite and other sulfide minerals) in coals, although a significant amount of arsenic is associated with organic matter. The accumulation of As in coal is controlled by many geological factors during coal-forming processes, including plant decomposition, sedimentary environments, and epigenetic hydrothermal activity. During the combustion of coal, As is released to the air, water, and soil, causing serious environmental pollution. More than 45% of the coal consumed in China is utilized by power plants, and it is estimated that nearly 522 tonnes, 21 tonnes and 252 tonnes of As are emitted into the atmosphere by industries, residential buildings and coal-fired power plants, respectively, every year. PMID- 22078372 TI - Mercury emission inventory and its spatial characteristics in the Pearl River Delta region, China. AB - A 3 km * 3 km gridded mercury emission inventory in the Pearl River Delta (PRD) region for 2008 was compiled from the best available emission factors and official statistical data. The inventory presented a comprehensive estimation of anthropogenic mercury sources and roughly estimated the emissions from natural sources. The total mercury emissions in the PRD region for the year of 2008 are estimated to be 17,244 kg, of which 85% released as Hg(0), 11% as Hg(2+), and 4% as Hg(P). Anthropogenic activities are dominant sources, accounting for 91% of the total emissions, while natural sources constitute the remaining emissions. Ranking by cities, Foshan produces the largest mercury emissions, followed by Dongguan, Guangzhou and Jiangmen. Coal combustion, municipal solid waste (MSW) incineration, fluorescent lamp and battery production are dominant contributors, responsible for 28%, 21%, 19% and 16% of the anthropogenic emissions, respectively. The high contribution of MSW incineration results from the rapid growth of MSW incineration in this region, reflecting a new trend of mercury emissions in China, especially in the fast developing regions. This implies the urgent need for further investigation of mercury emissions and the importance of controlling mercury emissions from MSW incineration. PMID- 22078373 TI - Dendritic cell lineage commitment is instructed by distinct cytokine signals. AB - Dendritic cells (DC) develop from hematopoietic stem cells, which is guided by instructive signals through cytokines. DC development progresses from multipotent progenitors (MPP) via common DC progenitors (CDP) into DC. Flt3 ligand (Flt3L) signaling via the Flt3/Stat3 pathway is of pivotal importance for DC development under steady state conditions. Additional factors produced during steady state or inflammation, such as TGF-beta1 or GM-CSF, also influence the differentiation potential of MPP and CDP. Here, we studied how gp130, GM-CSF and TGF-beta1 signaling influence DC lineage commitment from MPP to CDP and further into DC. We observed that activation of gp130 signaling promotes expansion of MPP. Additionally, gp130 signaling inhibited Flt3L-driven DC differentiation, but had little effect on GM-CSF-driven DC development. The inflammatory cytokine GM-CSF induces differentiation of MPP into inflammatory DC and blocks steady state DC development. Global transcriptome analysis revealed a GM-CSF-driven gene expression repertoire that primes MPP for differentiation into inflammatory DC. Finally, TGF-beta1 induces expression of DC-lineage affiliated genes in MPP, including Flt3, Irf-4 and Irf-8. Under inflammatory conditions, however, the effect of TGF-beta1 is altered: Flt3 is not upregulated, indicating that an inflammatory environment inhibits steady state DC development. Altogether, our data indicate that distinct cytokine signals produced during steady state or inflammation have a different outcome on DC lineage commitment and differentiation. PMID- 22078374 TI - Interaction between boron and aluminum and their effects on phenolic metabolism of Linum usitatissimum L. roots. AB - Aluminum toxicity is the most important limiting factor for plant growth and development in acidic soils (pH < 5.5). Inhibition of root growth has been considered as a sensitive marker of aluminum toxicity and the best indicator of boron deficiency as well. On the other hand cell wall phenolics (lignin and phenolic acids) have important roles in the reduction of extensibility of cell wall under stress conditions. Therefore, the interaction between boron and aluminum on phenolic compounds and the activity of the enzymes involved in their biosynthesis were investigated in flax seedlings. The seedlings were grown in Hoagland's solution and were treated with 3 B levels (4.5, 45 and 450 MUM of H3BO3 at deficient, normal, and excess conditions, respectively) and 3 Al levels (0, 50 and 100 MUM of AlCl3.6H2O). The results showed that Al treatment did not affect B content of roots (B content of Al-treated and non-treated plants were identical), while B treatment, particularly in higher concentrations, decreased Al content of roots compared with the control plants. In addition, the highest B concentration prevented the inhibitory effect of Al on the root length of plants. High concentrations of B also resulted in the decrease of enzyme activities involved in phenolic compounds (i.e., phenylalanine ammonia-lyase, polyphenol oxidase and peroxidase), decrease of lignin content and wall-bound phenols under Al stress, thereby ameliorating Al toxicity. The results suggest that the requirement of flax plants for B under Al stress conditions is higher than that required for growth in normal conditions without Al. PMID- 22078375 TI - Induced over-expression of the transcription factor OsDREB2A improves drought tolerance in rice. AB - The DREB and CBF transcription factors play a critical role in plant development and abiotic stress responses and, therefore, represent attractive targets for a molecular plant breeding approach. In this study, the rice OsDREB2A gene was isolated and expressed under the control of a stress-inducible promoter (4ABRC) to improve the abiotic stress tolerance of japonica rice variety TNG67. T2 and T3 transgenic lines over-expressing OsDREB2A were found to have improved survival rates under severe drought and salt stress conditions relative to non-transgenic rice plants or rice plants transformed with the empty vector control. OsDREB2A expression was found to be markedly induced by drought and ABA treatment. The results indicate that the induced over-expression of OsDREB2A driven by the 4ABRC promoter in engineered rice plants may protect cells during stress. PMID- 22078376 TI - Variegation in Arum italicum leaves. A structural-functional study. AB - The presence of pale-green flecks on leaves (speckling) is a frequent character among herbaceous species from shady places and is usually due to local loosening of palisade tissue (air space type of variegation). In the winter-green Arum italicum L. (Araceae), dark-green areas of variegated leaf blades are ca. 400 MUm thick with a chlorophyll content of 1080 mg m-2 and a palisade parenchyma consisting of a double layer of oblong cells. Pale-green areas are 25% thinner, have 26% less chlorophyll and contain a single, loose layer of short palisade cells. Full-green leaves generally present only one compact layer of cylindrical palisade cells and the same pigment content as dark-green sectors, but the leaf blade is 13% thinner. A spongy parenchyma with extensive air space is present in all leaf types. Green cells of all tissues have normal chloroplasts. Assays of photosynthetic activities by chlorophyll fluorescence imaging and O2 exchange measurements showed that variegated pale-green and dark-green sectors as well as full-green leaves have comparable photosynthetic activities on a leaf area basis at saturating illumination. However, full-green leaves require a higher saturating light with respect to variegated sectors, and pale-green sectors support relatively higher photosynthesis rates on a chlorophyll basis. We conclude that i) variegation in this species depends on number and organization of palisade cell layers and can be defined as a "variable palisade" type, and ii) the variegated habit has no limiting effects on the photosynthetic energy budget of A. italicum, consistent with the presence of variegated plants side by side to full-green ones in natural populations. PMID- 22078377 TI - Differential salinity-induced variations in the activity of H+-pumps and Na+/H+ antiporters that are involved in cytoplasm ion homeostasis as a function of genotype and tolerance level in rice cell lines. AB - The characterisation of cellular responses to salinity in staple crops is necessary for the reliable identification of physiological markers of salinity tolerance. Under saline conditions, variations in proton gradients that are generated by membrane-bound H+ pumps are crucial for maintaining cytoplasm homeostasis. We examined short (15 h) and longer term effects (4 days) of NaCl stress on the H+ pumping activities that are associated with the plasma membrane (P-ATPase) and the tonoplast (V-ATPase and V-PPase) in rice (Oryza sativa L.) callus lines that displayed different levels of NaCl tolerance and were established from two japonica rice cultivars. The applied stress conditions were based on those that were used in the induction of a stress-responsive polyubiquitin gene promoter (UBI1) in transgenic rice calli. The most remarkable effect of NaCl stress on H+ pumping was the rapid activation of tonoplast-bound pumps; this was particularly observed in cv. Bomba, in which the response of the P-ATPase was slower and showed a higher level of activity after 4 days of stress. The responses were cultivar-dependent; however, in general, a stronger activation occurred in the lines that had a higher tolerance (L-T) than in the less-tolerant (L-S) lines. Substrate hydrolysis was less affected than H+ pumping, and it yielded higher H+/substrate coupling ratios, which is indicative of an enhanced H+ pumping efficiency under saline conditions. The Na+/H+ antiport activity was generally limited to salt-stressed calli, and higher values and stronger activation of the tonoplast antiporter were observed in the L-T lines than in the L-S lines. The results that were obtained with the NaCl-stressed transgenic lines confirmed the close relationship between metabolic activity, H+ pumping and the induction of Na+/H+ exchange activities. PMID- 22078378 TI - Differential responses of the antioxidant defence system and ultrastructure in a salt-adapted potato cell line. AB - Changes in lipid peroxidation and ion content and the possible involvement of the antioxidant system in salt tolerance at the cellular level was studied in a potato (Solanum tuberosum L.) callus line grown on 150 mM NaCl (salt-adapted) and in a non-adapted line exposed to 150 mM NaCl (salt-stressed). Salinity reduced the growth rate and increased lipid peroxidation in salt-stressed line, which remained unaltered in the adapted line. Na+ and Cl- content increased due to salinity in both lines, but the adapted line displayed greater K+/Na+ ratio than the stressed one. Total superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), and glutathione reductase (GR, EC 1.6.4.2) activities decreased in both salt-exposed lines; catalase (CAT, EC 1.11.1.6) activity did not change in the adapted line, but decreased in the stressed cell line. Salinity caused the suppression of one GR isoform, while the isozyme patterns of SOD, APX, and CAT were not affected. Ascorbate and reduced glutathione increased in both salt-exposed calli lines. alpha-Tocopherol increased as a result of salt exposure, with higher levels found in adapted calli. Electron microscopy showed that neither the structural integrity of the cells nor membrane structure were affected by salinity, but plastids from adapted cells had higher starch content. The results suggest that the enzymic and non enzymic components of the antioxidant system are differentially modulated by salt. Different concentrations of antioxidant metabolites are more relevant to the adaptive response to salinity in potato calli than the differences in activity of the antioxidant enzymes. PMID- 22078379 TI - Heat shock response in tomato brassinosteroid mutants indicates that thermotolerance is independent of brassinosteroid homeostasis. AB - Brassinosteroids (BRs) are plant steroid hormones and, when applied exogenously, they induce physiological responses, including tolerance to heat shock (HS). How endogenous BR content and altered perception of BRs influence thermal tolerance is poorly understood. BR-induced thermotolerance in tomato seedlings with altered BR homeostasis was examined by assessing the survival, ion leakage and lipid peroxidation of seedlings from a BR-deficient mutant (extreme dwarf d(x)), a partially BR-insensitive mutant curl3(-abs) allele (curl3 altered brassinolide sensitivity) and a line overexpressing the Dwarf, BR-biosynthesis gene (35SD). We confirmed that treatment with 1 MUM of epi-brassinolide (EBL) induces thermotolerance of wild type seedlings following a HS regime at 45 degrees C. The curl3(-abs) seedlings had the highest basal tolerance to heat, whereas the EBL-induced thermal tolerance of d(x) seedlings was greatest and responded to lower EBL concentrations. The d(x) and 35SD seedlings had similar thermal tolerance; however, they showed increased signs of oxidative stress. EBL reduced the induction of lipid peroxidation of seedlings after recovery from heat. Highest oxidative stress and peroxidase (POX) activity (EC 1.11.1.7) was in BR deficient d(x) mutant seedlings. EBL was able of inducing POX activity but not other antioxidant enzymes; however, effects of HS on POX activity of seedlings were absent or less marked. Taking together, results indicate that thermal tolerance is independent of endogenous BR content, but HS-mediated oxidative stress depends on BR levels. PMID- 22078380 TI - HbMyb1, a Myb transcription factor from Hevea brasiliensis, suppresses stress induced cell death in transgenic tobacco. AB - Tapping panel dryness (TPD) is a complex physiological syndrome found widely in rubber tree (Hevea brasiliensis) plantations that causes severe yield loss in natural rubber-producing countries. In an earlier study, we confirmed that there is a negative correlation between HbMyb1 expression and TPD severity. To further investigate the function of HbMyb1 in TPD, HbMyb1 was over-expressed in tobacco controlled by a CaMV 35S promoter. In transgenic plants expressing HbMyb1, cell death induced by UV-B irradiation, paraquat and the hypersensitive reaction to necrotrophic fungal infection (Botrytis cinerea) was suppressed with a close correlation between HbMyb1 protein levels and the extent of suppression. In addition the nuclear condensation and degradation were observed in laticifer cells of TPD trees, while the nucleus of laticifer cells of healthy trees was morphologically normal. On the basis of the results described above, we propose that HbMyb1 maybe suppress stress induced cell death in rubber trees. PMID- 22078381 TI - SCOF-1-expressing transgenic sweetpotato plants show enhanced tolerance to low temperature stress. AB - Low-temperature stress represents one of the principal limitations affecting the distribution and productivity of many plant species, including crops such as sweetpotato. Transgenic sweetpotato (Ipomoea batatas L. cv. Yulmi) plants expressing the soybean cold-inducible zinc finger protein (SCOF-1) under control of an oxidative stress-inducible peroxidase (SWPA2) promoter (referred to as SF plants), were developed and evaluated for enhanced tolerance to low-temperature conditions. Following 4 degrees C treatment of SF plants, SCOF-1 expression correlated positively with tolerance to low-temperature stress at the leaf disc level. Increased SCOF-1 expression also correlated with enhanced tolerance to different low-temperature treatments at the whole plant level. SF plants treated with low-temperature stress (4 or 10 degrees C for 30 h) exhibited less of a reduction in photosynthetic activity and lipid peroxidation levels than non transgenic (NT) plants. Furthermore, the photosynthetic activity and lipid peroxidation levels of SF plants recovered to near pre-stress levels after 12 h of recovery at 25 degrees C. In contrast, these activities remained at a reduced level in NT plants after the same recovery period. Thus, this study has shown that low-temperature stress in sweetpotato can be efficiently modulated by overexpression of SCOF-1. PMID- 22078382 TI - Effect of root age on the allocation of metals, amino acids and sugars in different cell fractions of the perennial grass Paspalum notatum (bahiagrass). AB - This work aimed to compare the allocation of Al, Fe, Cu, Ni, amino acids and sugars in different fractions of root cells of Paspalum notatum with 21 and 120 days old grown in quartz sand. In general younger roots showed a higher content of Al, Fe, Cu Ni, amino acids and sugars, compared to older roots. This can be due to a higher metabolic activity of younger roots and/or to structural changes that can occur with cell ageing. Al and Fe were mainly allocated to fractions with pectin, hemicellulose and cellulose, both in younger and older roots. However, older roots also showed a significant fraction of Al allocated to the intracellular fraction. It seems that older roots were less able to prevent the entry of Al in the cytoplasm. The proportion of Cu was higher in intracellular components, both in younger and older roots, as expected from an essential nutrient. Ni content was very low in older roots and in younger roots it was mainly allocated to the intracellular fraction and to the cell wall polysaccharides fraction. The amino acids were mainly allocated to the cytoplasm and polysaccharide fraction. Although younger roots showed a higher total amount of amino acids compared to older roots, the amino acids profile and allocation, mainly in the cytoplasm polysaccharides, was quite similar. Arabinose, a major component of structural glycoproteins of the primary cell wall matrix, was only detected in younger roots. Thus, it seems that root cells of P. notatum suffered changes in the composition of the cell wall components with ageing. To further understand the structural changes of root cells with ageing and its effect on metal allocation, it is important to quantify several components of the cell wall matrix, namely pectins and glycoproteins. PMID- 22078383 TI - Induced accumulation of cuticular waxes enhances drought tolerance in Arabidopsis by changes in development of stomata. AB - Cuticular waxes are involved in the regulation of the exchange of gases and water in plants and can impact tolerance to drought. However, the molecular mechanisms of the relationship between wax accumulation and drought tolerance are largely unknown. We applied the methoxyfenozide gene switching system to regulate expression of the WIN1/SHN1 gene (WAX INDUCER 1/SHINE1; At1G15360), a transcriptional activator, to regulate production of cuticular waxes and cutin and followed changes of gene expression, metabolites, and drought tolerance. Treatment with the inducer resulted in expression of the target gene and specific downstream genes, and gradually increased cuticular waxes. Induction of cuticular wax conferred tolerance to drought and recovery from drought, and was correlated with reduced numbers of stomata. Quantitative RT-PCR assays using RNAs from transgenic plants revealed that when expression of the WIN1/SHN1 gene was induced there was increased expression of genes involved in wax development, and reduced expression of selected genes, including SPCH (At5g53210); MUTE (At3g06120); and FAMA (At3g241400); and YODA (At1g63700), each of which is involved in stomatal development. These studies suggest that drought tolerance caused by the induction of WIN1/SHIN gene may be due to reduced numbers of stomata as well as to cuticular wax accumulation. PMID- 22078384 TI - Exogenous nitrate induces root branching and inhibits primary root growth in Capsicum chinense Jacq. AB - The effects of nitrate (NO3-) on the root system are complex and depend on several factors, such as the concentration available to the plant, endogenous nitrogen status and the sensitivity of the species. Though these effects have been widely documented on Arabidopsis and cereals, no reports are available in the Capsicum genus. In this paper, we have determined the effect of an exogenous in vitro application of this nutrient on root growth in habanero pepper (Capsicum chinense Jacq.). Exposure to NO3- inhibited primary root growth in both, dose- and time-dependent manners. The highest inhibition was attained with 0.1 mM NO3- between the fourth and fifth days of treatment. Inhibition of primary root growth was observed by exposing the root to both homogeneous and heterogeneous conditions of the nutrient; in contrast, ammonium was not able to induce similar changes. NO3--induced inhibition of primary root growth was reversed by treating the roots with IAA or NPA, a polar auxin transport inhibitor. Heterogeneous NO3- application stimulated the formation and elongation of lateral roots in the segment where the nutrient was present, and this response was influenced by exogenous phytohormones. These results demonstrate that habanero pepper responds to NO3- in a similar fashion to other species with certain particular differences. Therefore, studies in this model could help to elucidate the mechanisms by which roots respond to NO3- in fluctuating soil environments. PMID- 22078385 TI - Enhanced in vitro regeneration and change in photosynthetic pigments, biomass and proline content in Withania somnifera L. (Dunal) induced by copper and zinc ions. AB - In the present study the effect of inorganic nutrients (CuSO4 & ZnSO4) on morphogenic and biochemical responses from nodal explants in Withania somnifera L. was investigated. Incorporation of either Copper sulphate (25-200 MUM) or Zinc sulphate (50-500 MUM) in the optimized Murashige and Skoog (MS) medium highly influenced the shoot bud formation and subsequent elongation, which induced maximum percentage (95%) regeneration, number (61.7 +/- 0.25) of shoots with shoot length (5.46 +/- 0.16 cm) on CuSO4 (100 MUM) and maximum percentage regeneration (100%), number of shoots (66.1 +/- 0.96) with shoot length (6.24 +/- 0.21 cm) on ZnSO4 (300 MUM) after 12 weeks of culture. Healthy growing in vitro microshoots rooted efficiently on 1/2 MS medium supplemented with NAA (0.5 MUM), which induced (16.2 +/- 0.12) roots with root length (3.30 +/- 0.12 cm) after 4 weeks. Pigment content increased with increasing concentration of Cu and Zn and the maximum Chl. a (0.47), (0.41); Chl. b (0.52), (0.42); total Chl. (0.99), (0.83) and Carotenoid (0.16), (0.16) mg/g FW contents in regenerants were found on CuSO4 (100 MUM) and ZnSO4 (300 MUM), respectively. Maximum proline content (0.17), (0.16) MUg/g FW was observed on high concentrations of CuSO4 (200 MUM) and ZnSO4 (500 MUM) respectively, in the basal medium. Regenerated plantlets were acclimatized successfully in soilrite with a survival rate of 95%. No morphological variations were detected among the micropropagated plants when compared with seedling raised plants of the same age. PMID- 22078387 TI - Improving the quality of reviews in veterinary science: the author's responsibility. PMID- 22078386 TI - Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (lncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of lncRNAs in patients' pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis. METHODS: Custom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative lncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of lncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of lncRNAs and to validate microarray results, respectively. RESULTS: We show that subsets of intronic/intergenic lncRNAs are expressed across tumor and non tumor pancreatic tissue samples. Enrichment of promoter-associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional.Statistically significant expression signatures comprising protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, loci harboring intronic lncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic lncRNAs (PPP3CB, MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time PCR. CONCLUSION: Our findings reveal sets of intronic lncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer. PMID- 22078388 TI - Investigation of the aetiology of udder-thigh dermatitis in French dairy cattle. AB - Udder-thigh dermatitis (UTD) is a common disease in dairy cattle. The aim of this study was to define UTD incidence, its risk factors and the involved pathogens. Of 74 respondents, 72 (97%) reported having had the disease. On those farms the incidence was 5.3 cases per 100 cow years. The odds ratio (OR) of UTD in primiparous compared to multiparous cows was 23.4 (95% CI 17.3-33.8). Compared to tied stalls, the ORs of UTD were 0.65 (95% CI 0.45-0.92) and 0.43 (95% CI 0.24 0.71) for free stalls and straw yards, respectively. Udder oedema was reported in 98.3% of cows with UTD. The most common bacteria isolated from affected skin were Fusobacterium spp. (12/14 cases). This study suggests that UTD management should focus on local treatment, reducing udder oedema and increasing exercise. PMID- 22078389 TI - Ultrasonographic appearance of bony abnormalities at the dorsal aspect of the fetlock joint in geriatric cadaver horses. AB - This article describes the ultrasonographic (US) appearance of bony abnormalities on the dorsal aspect of the third metacarpal/metatarsal bone of the equine fetlock in cadavers with radiographic signs of osteoarthrosis. After US, computed tomography was undertaken to better characterise the lesions. Twelve fetlock joints were collected and all had more than one bone abnormality on US. Normal subchondral bone appeared on US as a well-defined and regular hyperechoic line with distal acoustic shadowing. Bone abnormalities detected on US included (1) gaps in the proximal subchondral bone filled with material of heterogeneous echogenicity, (2) bone fragments represented as small straight smoothly delineated hyperechoic lines with distal shadowing located superficial to the surface of the adjacent bone, (3) proximal new bone formation visible as mild to severe cortical protrusions, (4) marginal osteophytoses seen as an elevation of the hyperechoic surface of the subchondral bone at the edges of the joint surfaces, (5) indentations in subchondral bone seen as a concave deviation of the hyperechoic line without interruption, (6) focal or diffuse irregularities of the subchondral bone seen as disruptions of the normal smooth bony contours, and (7) focal hyperechoic spikes originating from the subchondral plate and invading the articular cartilage. These findings are discussed. PMID- 22078390 TI - The mystery of sudden death in Williams-Beuren syndrome: cardiomyopathy or Kounis syndrome? PMID- 22078391 TI - Poliomyelitis and left ventricular hypertrabeculation (noncompaction). PMID- 22078392 TI - Optimal treatment of ACS patients: issues and considerations for upstream antiplatelet therapy. AB - Acute coronary syndromes (ACS) caused by atherosclerotic plaque rupture are clinically manifested as an ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, or unstable angina. Regardless of the management strategy chosen, antithrombotic therapy is necessary to optimize patient outcomes. The American College of Cardiology/American Heart Association guidelines provide a degree of flexibility in the use of antithrombotic and antiplatelet therapies; although this is largely influenced by the clinical severity of the ACS presentation, it can still be difficult for clinicians to decide which antiplatelet therapy regimen should be used. In this article, current recommendations for the use of antiplatelet therapy in the management of ACS are reviewed, along with an overview of the timing of upstream treatment and the decision points involved in choosing the appropriate antiplatelet regimen. PMID- 22078393 TI - Comparison of bleeding complications and one-year survival of low molecular weight heparin versus unfractioned heparin for acute myocardial infarction in elderly patients. The FAST-MI registry. AB - BACKGROUND: There are limited data on the safety and efficacy of low molecular weight heparin (LMWH) in elderly patients with acute myocardial infarction (AMI). METHODS: We aimed to compare LMWH with unfractioned heparin (UFH) in the management of AMI in elderly patients. FAST-MI is a nationwide registry carried out over a 1-month period in 2005, including consecutive patients with AMI admitted to intensive care unit <48 h from symptom onset in 223 participating centers. We assessed the impact of LMWH on bleeding, the need for blood transfusion and one-year survival in elderly patients (>= 75 years). RESULTS: 963 patients treated with heparin were included (mean age 82 +/- 5 years; 51% women; 42.5% ST-elevation myocardial infarction). Major bleeding (2.4% vs. 6.1%, P=0.004) and blood transfusions (4.6% vs. 9.7%, P=0.002) were significantly less frequent with LMWH compared with the UFH, a difference that persisted after multivariate adjustment (OR=0.41, 95% CI: 0.20-0.83 and OR=0.49, 95% CI: 0.28 0.85, respectively). One-year survival and stroke and reinfarction-free survival were also significantly higher with LMWH compared with UFH (OR=0.66, 95% CI: 0.50 0.85 and OR=0.71, 95% CI: 0.56-0.91, respectively). In two cohorts of patients matched on a propensity score for getting LMWH and with similar baseline characteristics (328 patients per group), major bleeding and transfusion were significantly lower while one-year survival was significantly higher in patients receiving LMWH. CONCLUSIONS: The present data show that in elderly patients admitted for AMI, use of LMWH is associated with less bleeding, less need for transfusion, and higher survival, compared with the use of UFH. PMID- 22078394 TI - Comparison of heart-type fatty acid binding protein and sensitive troponin for the diagnosis of early acute myocardial infarction. AB - BACKGROUND: The current development of serological biomarkers allows detection of smaller myocardial necrosis and early acute myocardial infarction (AMI). We evaluated the relevance of the heart-type fatty acid binding protein (H-FABP) assay, which has recently been approved in Japan, for early diagnosis of AMI as compared with the sensitive troponin assay. METHODS: This is an observational study in a single center. From 2010 July to 2011 January, 114 patients who presented with symptoms suggestive of AMI were enrolled. RESULTS: AMI was adjudicated in 45 patients (40%). The diagnostic accuracy of measurements obtained at presentation for AMI, as quantified by the area under the receiver operating-characteristic curve (AUC), was significantly lower with H-FABP assay than the sensitive troponin assay [AUC for H-FABP, 0.59; 95% confidence interval (CI) 0.48-0.70; and for troponin I, 0.89; 95% CI, 0.83-0.94; P<.0001]. Among patients who presented within 2h after the onset of chest pain, the AUC for H FABP was even low as compared with sensitive troponin (0.55; 0.39-0.72 vs. 0.89; 0.80-0.98, p<0.001). The clinical sensitivity for the diagnosis of AMI with the cutoff point of 99 th percentile was similar in both assays (81% and 81%, respectively), however, the specificity was extremely low in the H-FABP assay as compared with sensitive troponin assay (19% and 79%, respectively). CONCLUSION: The measurement of H-FABP in 114 consecutive patients with chest pain suggestive of AMI showed no improvement of diagnosis for early AMI as compared with the current sensitive troponin assay because of its extremely low specificity. PMID- 22078395 TI - Cross-cultural analysis of type D (distressed) personality in 6222 patients with ischemic heart disease: a study from the International HeartQoL Project. AB - BACKGROUND: Type D (distressed) personality, the conjoint effect of negative affectivity (NA) and social inhibition (SI), predicts adverse cardiovascular outcomes, and is assessed with the 14-item Type D Scale (DS14). However, potential cross-cultural differences in Type D have not been examined yet in a direct comparison of countries. AIM: To examine the cross-cultural validity of the Type D construct and its relation with cardiovascular risk factors, cardiac symptom severity, and depression/anxiety. METHODS: In 22 countries, 6222 patients with ischemic heart disease (angina, 33%; myocardial infarction, 37%; or heart failure, 30%) completed the DS14 as part of the International HeartQoL Project. RESULTS: Type D personality was assessed reliably across countries (alphaNA>.80; alphaSI>.74; except Russia, which was excluded from further analysis). Cross cultural measurement equivalence was established for Type D personality at all measurement levels, as the factor-item configuration, factor loadings, and error structure were not different across countries (fit: CFI=.91; NFI=.88; RMSEA=.018), as well as across gender and diagnostic subgroups. Type D personality was more prevalent in Southern (37%) and Eastern (35%) European countries compared to Northern (24%) and Western European and English-speaking (both 27%) countries (p<.001). Type D was not confounded by cardiac symptom severity, but was associated with a higher prevalence of hypertension, smoking, sedentary lifestyle, and depression. CONCLUSION: Cross-cultural measurement equivalence was demonstrated for the Type D scale in 21 countries. There is a pan cultural relationship between Type D personality and some cardiovascular risk factors, supporting the role of Type D personality across countries and cardiac conditions. PMID- 22078396 TI - Large and small artery endothelial dysfunction in chronic fatigue syndrome. PMID- 22078397 TI - Prevalence of atrial fibrillation in patients with history of paroxysmal supraventricular tachycardia. AB - OBJECTIVES: This study was performed to evaluate the prevalence of atrial fibrillation (AF) in patients seen for paroxysmal supraventricular tachycardia (PSVT) and to identify factors favoring AF. AF incidence is increased in patients with PSVT, but AF risk factors are unknown. POPULATION: 1187 patients, mean age 50 +/- 19 years, were consecutively studied for spontaneous PSVT confirmed by electrophysiological study (EPS). Patients with anterograde conduction through an accessory pathway were excluded. METHODS: Clinical factors, age, gender, heart disease (HD) and electrophysiological data were noted. Patients with and without AF were compared. Mean follow-up was 4.48 +/- 4.9 years. RESULTS: 61 patients developed documented paroxysmal or permanent AF or atrial flutter (5%). They were older than patients without AF (59 vs 49 years, p<0.0005), were more frequently men (59% vs 37%) (p<0.002), had more frequently prior AF (24.5% vs 0.5%) (p<0.0001) and associated HD (18% vs 5%) (p<0.004). There were no differences at EPS concerning the mechanism of re-entry. AF induction or occurrence during EPS was more frequent in patients with AF (31%) than in patients without AF (9%) (p<0.001). Multivariate analysis showed age, male gender, prior AF, HD and atrial vulnerability during EPS were independent predictors of AF. Univariate comparison between both groups suggests no effect of PSVT ablation on the incidence of AF. CONCLUSIONS: The prevalence of AF in our population was only 5%. The risk of AF was correlated with the classical risk factors of AF and atrial vulnerability during electrophysiological study. Patients with these risk factors should be followed. PMID- 22078398 TI - Successful shunt closure and improvement of hemodynamics in an ASD patient with severe pulmonary arterial hypertension and small shunt following a long-term use of bosentan. PMID- 22078399 TI - Hypertrophic cardiomyopathy or non-compaction? How the first impression can be wrong. PMID- 22078400 TI - Participation of mitochondrial permeability transition pore in the effects of ischemic preconditioning in hypertrophied hearts: role of NO and mitoKATP. AB - BACKGROUND: The mitochondrial permeability transition pore (mPTP) plays an important role in ischemia-reperfusion in normotensive animals. Our study aims to define their participation in the ischemic preconditioning (IP) in hypertrophied hearts and to assess the role played by NO and mitochondrial ATP-dependent K channels (mitoKATP). MATERIAL AND METHODS: Isolated hearts from spontaneously hypertensive rats (SHR) and age-matched normotensive rats Wistar Kyoto (WKY) were subjected to 35-min or 50-min global ischemia (GI) followed by 2-hour reperfusion (R). IP was induced by a single cycle of 5-min GI and 10-min R (IP1) or three cycles of 2-min GI and 5-min R (IP3) applied before to prolonged ischemia. L-NAME (NOS inhibitor) or 5-HD (mitoKATP blocker) to investigate the role played by NO and mitoKATP, respectively were administered. Infarct size (IS), myocardial function, reduced glutathione (GSH) - as marker of oxidative stress and MnSOD cytosolic activity - as an index of mPTP opening were determined. RESULTS: IP1 significantly decreased the IS in WKY hearts at both ischemia duration times. In SHR, IP1 decreased the IS observed in GI35 but it did not modify that detected at 50-min GI, which was limited by IP3. IP preserved GSH content and decreased MnSOD cytosolic activity in both rat strains. These protective effects were annulled by L-NAME and 5-HD for both ischemic periods in SHR, whereas in WKY they were only effective for 50-min GI. CONCLUSION: Our data demonstrate that the cardioprotection achieved by ischemic preconditioning in hearts from SHR hearts involves an attenuation of mPTP opening NO and mitoKATP-mediated. PMID- 22078401 TI - Systemic inflammation impairs cardiac glucose uptake. PMID- 22078402 TI - Inflammatory and anti-inflammatory indicators as predictive biomarkers of metabolic syndrome. PMID- 22078403 TI - [Spontaneous drainage of a pancreatic pseudocyst into the colon]. PMID- 22078404 TI - Molecular imaging of the small renal mass. PMID- 22078405 TI - Highlights of the 2010 SUO Annual Meeting. PMID- 22078406 TI - Warm ischemia less than 30 minutes is not necessarily safe during partial nephrectomy: every minute matters. AB - OBJECTIVE: At the 11th Annual Meeting of the Society of Urologic Oncology (SUO), an expert panel discussed the importance of warm ischemia time on renal function during partial nephrectomy. The position of this manuscript is that every minute of warm ischemia time has a deleterious effect on renal function outcomes following partial nephrectomy. MATERIALS AND METHODS: The presentation was derived from a review of the published urologic, nephrology, and transplant literature related to warm ischemia time and renal function outcomes. RESULTS: There exist numerous clinical models to study the effects of warm ischemia on renal function. These include the bilateral kidney, unilateral partial nephrectomy, solitary kidney partial nephrectomy, and transplant kidney model. Each of these models provides evidence for minimizing warm ischemia time to prevent acute renal failure, chronic kidney disease, and end stage renal failure. In the best available model, solitary kidney partial nephrectomy, each minute of warm ischemia was found to be associated with a 6% increased risk of acute renal failure, 7% increased risk of acute-onset end stage renal disease (ESRD), and 4% increased risk of new-onset ESRD while controlling for preoperative renal function, tumor size, and surgical approach. CONCLUSIONS: There is ample evidence, consistent across multiple human kidney models, supporting the potentially deleterious renal effects of warm ischemia during partial nephrectomy. There does not appear to be a known safe threshold of warm ischemia since each minute sequentially contributes to the risk of developing acute kidney injury and renal function decline. Ultimate renal function following PN is dependent on the "3 Qs": quality (renal function prior to surgery), quantity (renal parenchyma preserved during surgery), and quickness (ischemia time). PMID- 22078407 TI - Argument in favor of performing partial nephrectomy for tumors greater than 7 cm: the metastatic prescription has already been written. AB - The acceptance of partial nephrectomy over the past few decades has been gradual with initial utilization of nephron sparing approach for tumors up to 4 cm and more recently up to 7 cm. The arbitrary cutoff values used in the historic recommendations are based on the oncologic outcomes documenting the increase in metastatic potential of renal lesions that is strongly associated with increase in tumor size. Despite these observations, radical nephrectomy has not been found to be protective from development of metastatic disease, and oncologic outcomes of partial nephrectomy for tumors matched for size or stage have not been inferior to radical nephrectomy. The present manuscript argues for avoidance of specific size cutoffs as patients with larger masses may benefit from maximal preservation of nephrons. These are the very patients at higher risk for metastatic disease, who may benefit from preserved renal function to allow for future additional therapies or adjuvant trials. PMID- 22078408 TI - Surgical therapy for intermediate risk prostate cancer. AB - Optimal surgical management of intermediate risk prostate cancer has yet to be defined. This is in part due to the heterogeneity of the disease burden in this patient population. When choosing the surgical approach for intermediate risk prostate cancer, urologists should attempt to maximize oncologic outcomes while balancing quality of life concerns. Due to significant risk of failure following solo treatment, multi-modality therapy should be available for those patients with poor pathologic outcomes following surgical therapy. PMID- 22078409 TI - The management of subcentimeter residual mass in NSGCT: pcRPLND vs. observation. AB - Patients with advanced non-seminomatous germ cell tumors may achieve a serologic and radiographic complete response (CR) to first-line chemotherapy (defined as a residual mass < 1 cm in size). Recent reports suggest that these patients may be observed with a low rate of relapse but there remain compelling arguments for surgical excision. The arguments for and against post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) are presented. There is clear consensus that patient's with residual masses > 1 cm should undergo post chemotherapy surgery. PMID- 22078410 TI - Time-dependent slowly-reversible inhibition of monoamine oxidase A by N substituted 1,2,3,6-tetrahydropyridines. AB - A novel class of N-substituted tetrahydropyridine derivatives was found to have multiple kinetic mechanisms of monoamine oxidase A inhibition. Eleven structurally similar tetrahydropyridine derivatives were synthesized and evaluated as inhibitors of MAO-A and MAO-B. The most potent MAO-A inhibitor in the series, 2,4-dichlorophenoxypropyl analog 12, displayed time-dependent mixed noncompetitive inhibition. The inhibition was reversed by dialysis, indicating reversible enzyme inhibition. Evidence that the slow-binding inhibition of MAO-A with 12 involves a covalent bond was gained from stabilizing a covalent reversible intermediate product by reduction with sodium borohydride. The reduced enzyme complex was not reversible by dialysis. The results are consistent with slowly reversible, mechanism-based inhibition. Two tetrahydropyridine analogs that selectively inhibited MAO-A were characterized by kinetic mechanisms differing from the kinetic mechanism of 12. As reversible inhibitors of MAO-A, tetrahydropyridine analogs are at low risk of having an adverse effect of tyramine-induced hypertension. PMID- 22078411 TI - Structure-based rational design of novel hit compounds for pyruvate dehydrogenase multienzyme complex E1 components from Escherichia coli. AB - Pyruvate dehydrogenase multienzyme complex (PDHc) E1 component plays a pivotal role in cellular metabolism to convert the product of glycolysis (pyruvate) to acetyl-CoA, and has been reported as a potential target for anti-microbial and herbicide. In present study, based on the thiamin diphosphate (ThDP) site, four novel hit compounds with high inhibitory activity against the PDHc-E1 from Escherichia coli were firstly designed by using structure-based molecular docking methods. As expected, among four compounds, the compound 3a is the best inhibitor by far, with IC(50) value of 6.88 MUM against PDHc-E1 from E. coli. To elucidate the interaction mechanism between the active site of PDHc-E1 and its inhibitor, the docking-based molecular dynamics simulation (MD) and MD-based ab initio fragment molecular orbital (FMO) calculations were also further performed. The positive results indicated that all modeling strategies presented in the current study most like to be an encouraging way in design of novel lead compounds with structural diversity for PDHc-E1 in the future. PMID- 22078412 TI - Disulfide and amide-bridged cyclic peptide analogues of the VEGF81-91 fragment: synthesis, conformational analysis and biological evaluation. AB - The design, synthesis, conformational studies and binding affinity for VEGFR-1 receptors of a collection of linear and cyclic peptide analogues of the beta hairpin fragment VEGF(81-91) are described. Cyclic 11-mer peptide derivatives were prepared from linear precursors with conveniently located Cys, Asp or Dap residues, by the formation of disulfide and amide bridges, using solid-phase synthesis. Molecular modelling studies indicated a tendency to be structured around the central beta-turn of the VEGF(81-91) beta-hairpin in most synthesized cyclic compounds. This structural behavior was confirmed by NMR conformational analysis. The NHCO cyclic derivative 7 showed significant affinity for VEGFR-1, slightly higher than the native linear fragment, thus supporting the design of mimics of this fragment as a valid approach to disrupt the VEGF/VEGFR-1 interaction. PMID- 22078413 TI - Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid probes. AB - The formation of proteinaceous aggregates is a pathognomonic hallmark of several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. To date, the final diagnostic for these diseases can only be achieved by immunostaining of post-mortem brain tissues with the commonly used congo red and Thioflavin T/S amyloid-dyes. The interest in developing amyloid-avid radioprobes to be used for protein aggregates imaging by positron emission tomography has grown substantialy, due to the promise in assisting diagnosis of these disorders. To this purpose, the present work describes the synthesis and characterization of four novel fluorinated styryl benzazole derivatives 1-4 by means of the Wittig reaction, as well as their in vitro evaluation as amyloid-probing agents. All compounds were obtained as mixtures of geometric E and Z isomers, with the preferable formation of the E isomer. Photoisomerization reactions allowed for the maximization of the minor Z isomers. The authentic 1-4E/Z isomers were isolated after purification by column chromatography under dark conditions. Profiting from the fluorescence properties of the different geometric isomers of 1-4, their binding affinities towards amyloid fibrils of insulin, alpha-synuclein and beta-amyloid peptide were also measured. These compounds share similarities with Thioflavin T, interacting specifically with fibrillary species with a red shift in the excitation wavelengths along with an increase in the fluorescence emission intensity. Apparent binding constants were determined and ranged between 1.22 and 23.96 MUM(-1). The present data suggest that the novel fluorinated styryl benzazole derivatives may prove useful for the design of (18)F-labeled amyloid radioprobes. PMID- 22078414 TI - Small interfering RNA targeting mcl-1 enhances proteasome inhibitor-induced apoptosis in various solid malignant tumors. AB - BACKGROUND: Targeting the ubiquitin-proteasome pathway is a promising approach for anticancer strategies. Recently, we found Bik accumulation in cancer cell lines after they were treated with bortezomib. However, recent evidence indicates that proteasome inhibitors may also induce the accumulation of anti-apoptotic Bcl 2 family members. The current study was designed to analyze the levels of several anti-apoptotic members of Bcl-2 family in different human cancer cell lines after they were treated with proteasome inhibitors. METHODS: Different human cancer cell lines were treated with proteasome inhibitors. Western blot were used to investigate the expression of Mcl-1 and activation of mitochondrial apoptotic signaling. Cell viability was investigated using SRB assay, and induction of apoptosis was measured using flow cytometry. RESULTS: We found elevated Mcl-1 level in human colon cancer cell lines DLD1, LOVO, SW620, and HCT116; human ovarian cancer cell line SKOV3; and human lung cancer cell line H1299, but not in human breast cancer cell line MCF7 after they were treated with bortezomib. This dramatic Mcl-1 accumulation was also observed when cells were treated with other two proteasome inhibitors, MG132 and calpain inhibitor I (ALLN). Moreover, our results showed Mcl-1 accumulation was caused by stabilization of the protein against degradation. Reducing Mcl-1 accumulation by Mcl-1 siRNA reduced Mcl-1 accumulation and enhanced proteasome inhibitor-induced cell death and apoptosis, as evidenced by the increased cleavage of caspase-9, caspase-3, and poly (ADP ribose) polymerase. CONCLUSIONS: Our results showed that it was not only Bik but also Mcl-1 accumulation during the treatment of proteasome inhibitors, and combining proteasome inhibitors with Mcl-1 siRNA would enhance the ultimate anticancer effect suggesting this combination might be a more effective strategy for cancer therapy. PMID- 22078416 TI - Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody. AB - OBJECTIVES: The aims of the present study were to (1) assess clinical features and long-term outcome in anti-Jo1-positive patients with anti-Ro52 antibody; (2) compare characteristics of anti-Jo1-positive patients with and without anti-Ro52 antibody; and (3) compare features of anti-Ro52-positive patients with and without anti-Jo1 antibody. METHODS: The medical records of 89 consecutive anti Jo1-positive patients with antisynthetase syndrome (ASS) were reviewed; 36 of these patients had coexistent anti-Ro52 antibody. Furthermore, the medical records of 13 consecutive anti-Ro52-positive patients without anti-Jo1 antibody were also reviewed. RESULTS: Nine anti-Jo1-positive patients (25%) with anti-Ro 52 antibody achieved remission of ASS, whereas 19 other patients (52.8%) improved and 8 patients (22.2%) worsened their clinical status. Anti-Jo1-positive patients with anti-Ro52 antibody experienced ASS-related complications: interstitial lung disease (n = 28), esophageal dysfunction (n = 9), and joint manifestations (n = 25), including periarticular hydroxyapatite calcifications and erosions of metacarpophalangeal and interphalangeal joints and wrists (n = 3); 7 anti-Ro52 positive patients (19.4%) had cancer. Anti-Jo1-positive patients with anti-Ro52 antibody, compared with those without, more commonly experienced deterioration of myositis and joint involvement, symptomatic form of ILD, and cancer; they also had decreased survival rate (P = 0.05). We further found that anti-Ro52-positive patients with anti-Jo1 antibody, compared with those without, were younger and more frequently exhibited ILD with poorer prognosis. CONCLUSIONS: Our series underlines that the presence of anti-Ro52 antibody is associated with a particular phenotype of ASS, leading to more severe myositis and joint impairment. Moreover, the coexistence of anti-Ro52 antibody seems to be associated with an increased risk of cancer. We therefore suggest that anti-Jo1 positive patients should routinely undergo the search for anti-Ro52 antibody, as this autoantibody appears to impact patients' prognosis. PMID- 22078415 TI - Aflatoxin levels, plasma vitamins A and E concentrations, and their association with HIV and hepatitis B virus infections in Ghanaians: a cross-sectional study. AB - BACKGROUND: Micronutrient deficiencies occur commonly in people infected with the human immunodeficiency virus. Since aflatoxin exposure also results in reduced levels of several micronutrients, HIV and aflatoxin may work synergistically to increase micronutrient deficiencies. However, there has been no report on the association between aflatoxin exposure and micronutrient deficiencies in HIV infected people. We measured aflatoxin B1 albumin (AF-ALB) adduct levels and vitamins A and E concentrations in the plasma of HIV-positive and HIV-negative Ghanaians and examined the association of vitamins A and E with HIV status, aflatoxin levels and hepatitis B virus (HBV) infection. METHODS: A cross sectional study was conducted in which participants completed a demographic survey and gave a 20 mL blood sample for analysis of AF-ALB levels, vitamins A and E concentrations, CD4 counts, HIV viral load and HBV infection. RESULTS: HIV infected participants had significantly higher AF-ALB levels (median for HIV positive and HIV-negative participants was 0.93 and 0.80 pmol/mg albumin, respectively; p <0.01) and significantly lower levels of vitamin A (-16.94 MUg/dL; p <0.0001) and vitamin E (-0.22 mg/dL; p <0.001). For the total study group, higher AF-ALB was associated with significantly lower vitamin A (-4.83 MUg/dL for every 0.1 pmol/mg increase in AF-ALB). HBV-infected people had significantly lower vitamin A (-5.66 MUg/dL; p = 0.01). Vitamins A and E levels were inversely associated with HIV viral load (p = 0.02 for each), and low vitamin E was associated with lower CD4 counts (p = 0.004). CONCLUSIONS: Our finding of the significant decrease in vitamin A associated with AF-ALB suggests that aflatoxin exposure significantly compromises the micronutrient status of people who are already facing overwhelming health problems, including HIV infection. PMID- 22078417 TI - Feasibility of using a handheld electronic device for the collection of patient reported outcomes data from children. AB - The manner in which a communication disorder affects health-related quality of life (QOL) in children is not known. Unfortunately, collection of quality of life data via traditional paper measures is labor intensive and has several other limitations, which hinder the investigation of pediatric quality of life in children. Currently, there is not sufficient research regarding the use of electronic devices to collect pediatric patient reported outcomes in order to address such limitations. Thus, we used a cross-over design to compare responses to a pediatric health quality of life instrument (PedsQL 4.0) delivered using a handheld electronic device to those from a traditional paper form. Respondents were children with (n=9) and without (n=10) a speech or voice disorder. For paper versus the electronic format, we examined time to completion, number of incomplete or inaccurate question responses, intra-rater reliability, ease of use, and child and parent preference. There were no significant differences between children's scores, time to complete the measure, or ratings related to ease of answering questions. The percentage of children who made answering errors or omissions with paper and pencil was significantly greater than the percentage of children who made such errors using the device. This preliminary study demonstrated that use of an electronic device to collect QOL or patient-reported outcomes (PRO) data from children is more efficient than and just as feasible, reliable, and acceptable as using paper forms. The development of hardware and software applications for the collection of QOL and/or PRO data in children with speech disorders is likely warranted. LEARNING OUTCOMES: The reader will be able to understand: (1) The potential benefits of using electronic data capture via handheld devices for collecting pediatric patient reported outcomes; (2) The Pediatric Quality of Life Inventory 4.0 is a measure of the perception of general health quality that has distinguished between healthy children and those with chronic health conditions; (3) Past research in communication disorders indicates that voice and speech disorders may impact quality of life in children; (4) Based on preliminary data, electronic collection of patient reported outcomes in children with and without speech/voice disorders is more efficient and equally feasible, reliable, and acceptable when compared to paper forms. PMID- 22078418 TI - Tocilizumab treatment for neuro-Behcet's disease, the first report. PMID- 22078419 TI - Stroke associated with surgical and transcatheter treatment of aortic stenosis: a comprehensive review. AB - Stroke is a potential complication of treating patients with aortic stenosis via surgical aortic valve replacement (AVR), transcatheter aortic valve replacement (TAVR), and balloon aortic valvuloplasty. Because there are limited and heterogeneous data on the incidence, risk factors, and outcomes of stroke among patients being treated for aortic stenosis, we performed a comprehensive review of the literature. The risk of stroke after AVR in the general population is approximately 1.5%, and the risk is increased (to approximately 2% to 4%) in older and higher-risk patients. Strokes were reported in 1.5% to 6% of patients treated with TAVR, and in the only randomized trial of AVR versus TAVR, there was an increased risk of 30-day strokes (minor and major strokes and transient ischemic attacks) with TAVR (5.5% vs. 2.4%, p = 0.04). PMID- 22078420 TI - Clinical outcomes of patients with severe aortic stenosis at increased surgical risk according to treatment modality. AB - OBJECTIVES: The aim of this study was to assess the role of transcatheter aortic valve implantation (TAVI) compared with medical treatment (MT) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) at increased surgical risk. BACKGROUND: Elderly patients with comorbidities are at considerable risk for SAVR. METHODS: Since July 2007, 442 patients with severe AS (age: 81.7 +/- 6.0 years, mean logistic European System for Cardiac Operative Risk Evaluation: 22.3 +/- 14.6%) underwent treatment allocation to MT (n = 78), SAVR (n = 107), or TAVI (n = 257) on the basis of a comprehensive evaluation protocol as part of a prospective registry. RESULTS: Baseline clinical characteristics were similar among patients allocated to MT and TAVI, whereas patients allocated to SAVR were younger (p < 0.001) and had a lower predicted peri-operative risk (p < 0.001). Unadjusted rates of all-cause mortality at 30 months were lower for SAVR (22.4%) and TAVI (22.6%) compared with MT (61.5%, p < 0.001). Adjusted hazard ratios for death were 0.51 (95% confidence interval: 0.30 to 0.87) for SAVR compared with MT and 0.38 (95% confidence interval: 0.25 to 0.58) for TAVI compared with MT. Medical treatment (<0.001), older age (>80 years, p = 0.01), peripheral vascular disease (<0.001), and atrial fibrillation (p = 0.04) were significantly associated with all-cause mortality at 30 months in the multivariate analysis. At 1 year, more patients undergoing SAVR (92.3%) or TAVI (93.2%) had New York Heart Association functional class I/II as compared with patients with MT (70.8%, p = 0.003). CONCLUSIONS: Among patients with severe AS with increased surgical risk, SAVR and TAVI improve survival and symptoms compared with MT. Clinical outcomes of TAVI and SAVR seem similar among carefully selected patients with severe symptomatic AS at increased risk. PMID- 22078421 TI - Are you too young? PMID- 22078422 TI - Multimodality imaging in transcatheter aortic valve implantation and post procedural aortic regurgitation: comparison among cardiovascular magnetic resonance, cardiac computed tomography, and echocardiography. AB - OBJECTIVES: The purpose of this study was to determine imaging predictors of aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) and the agreement and reproducibility of cardiovascular magnetic resonance (CMR), cardiac computed tomography (CCT), and transthoracic echocardiography (TTE) in aortic root assessment. BACKGROUND: The optimal imaging strategy for planning TAVI is unclear with a paucity of comparative multimodality imaging data. The association between aortic root morphology and outcomes after TAVI also remains incompletely understood. METHODS: A total of 202 consecutive patients assessed by CMR, CCT, and TTE for TAVI were studied. Agreement and variability among and within imaging modalities was assessed by Bland-Altman analysis. Postoperative AR was assessed by TTE. RESULTS: Of the 202 patients undergoing TAVI assessment with both CMR and TTE, 133 also underwent CCT. Close agreement was observed between CMR and CCT in dimensions of the aortic annulus (bias, -0.4 mm; 95% limits of agreement: -5.7 to 5.0 mm), and similarly for sinus of Valsalva, sinotubular junction, and ascending aortic measures. Agreement between TTE-derived measures and either CMR or CCT was less precise. Intraobserver and interobserver variability were lowest with CMR. The presence and severity of AR after TAVI were associated with larger aortic valve annulus measurements by both CMR (p = 0.03) and CCT (p = 0.04) but not TTE-derived measures (p = 0.10). Neither CCT nor CMR measures of annulus eccentricity, however, predicted AR after TAVI (p = 0.33 and p = 0.78, respectively). CONCLUSIONS: In patients undergoing imaging assessment for TAVI, the presence and severity of AR after TAVI were associated with larger aortic annulus measurements by both CMR and CCT, but not TTE. Both CMR and CCT provide highly reproducible information in the assessment of patients undergoing TAVI. PMID- 22078423 TI - The evolution from surgery to percutaneous mitral valve interventions: the role of the edge-to-edge technique. AB - The edge-to-edge technique is a versatile procedure for mitral valve repair. Its technical simplicity has been the prerequisite for the development of a number of transcatheter technologies to perform percutaneous mitral valve repair. The evolution from a standard open heart surgical to percutaneous procedure involved the application of the technique in minimally invasive robotic surgery and direct access (transatrial) off-pump suture-based repair and finally in the fully percutaneous approach with either suture-based or device (clip)-based approach. The MitraClip (Abbott Vascular, Menlo Park, California) is currently available for clinical use in Europe, and it is mainly applied to treat high-risk patients with functional mitral regurgitation. A critical review of the surgical as well as the early percutaneous repair data is necessary to elucidate the clinical role and the potential for future developments of the edge-to-edge repair in the treatment of mitral regurgitation. PMID- 22078424 TI - Correction of mitral regurgitation in nonresponders to cardiac resynchronization therapy by MitraClip improves symptoms and promotes reverse remodeling. AB - OBJECTIVES: This study evaluated the safety, efficacy, and effect of MitraClip treatment on symptoms and left ventricular (LV) remodeling in nonresponders to cardiac resynchronization therapy (CRT). BACKGROUND: Moderate to severe functional mitral regurgitation (FMR) frequently persists after CRT, contributing to reduced or no response to CRT. Percutaneous repair with the MitraClip has been proposed as an additional therapeutic option in select patients with significant FMR. METHODS: Fifty-one severely symptomatic CRT nonresponders with significant FMR (grade >=2, 100%) underwent MitraClip treatment. Changes in New York Heart Association functional class, degree of FMR, LV ejection fraction (EF), and LV end-diastolic/end-systolic volumes (EDV/ESV) before and after (3, 6, and 12 months) MitraClip implantation were recorded. Mortality data, including cause of death, were collected. RESULTS: MC treatment was feasible in all patients (49% 1 clip, 46% 2 clips). There were 2 periprocedural deaths. Median follow-up was 14 months (25th to 75th percentile: 8 to 17 months). New York Heart Association functional class improved acutely at discharge (73%) and continued to improve progressively during follow-up (regression model, p < 0.001). The proportion of patients with significant residual FMR (grade >=2) progressively decreased during follow-up (regression model, p < 0.001). Reverse LV remodeling and improved LVEF were detected at 6 months, with further improvement at 12 months (regression model, p = 0.001, p = 0.008, and p = 0.031 for ESV, EDV, and LVEF, respectively). Overall 30-day mortality was 4.2%. Overall mortality during follow-up was 19.9 per 100 person-years (95% confidence interval: 10.3 to 38.3). Nonsurvivors had more compromised clinical baseline conditions, longer QRS duration, and a more dilated heart. CONCLUSIONS: FMR treatment with the MitraClip in CRT nonresponders was feasible, safe, and demonstrated improved functional class, increased LVEF, and reduced ventricular volumes in about 70% of these study patients. PMID- 22078425 TI - Echocardiographic and clinical outcomes of MitraClip therapy in patients not amenable to surgery. AB - OBJECTIVES: The aim of this study was to assess the outcomes of patients at prohibitive surgical risk undergoing MitraClip therapy (Abbott Vascular, Redwood City, California) for severe mitral regurgitation (MR). BACKGROUND: The safety of percutaneous mitral valve repair has been documented. However, midterm development of mitral valve function, ventricular remodeling, and clinical outcomes in patients not amenable to surgery are unknown. METHODS: A total of 104 consecutive patients (mean age 74 +/- 9 years; 64 men; 49 and 54 with MR 3+ and 4+, respectively; 69 with functional MR; 59 and 45 in New York Heart Association classes III and IV, respectively) were followed for a median of 359 days. RESULTS: Device success was achieved in 96 patients (92%). In patients with successful index procedures, MR grade <=2+ was present at follow-up in 82.5%, left ventricular end-diastolic and -systolic volumes were reduced, and forward stroke volumes were significantly increased. Improvements in New York Heart Association functional class were observed in 80% of patients, with 69% in class I or II; 75% improved in the 6-min walk test; and 74% reported improvements in quality of life. One-year estimates of mortality and rehospitalization were 22% and 31%, respectively. Forward stroke volume at discharge emerged as a predictor of event-free survival. CONCLUSIONS: MitraClip therapy improves clinical and echocardiographic outcomes at 1 year in about three-quarters of critically ill, elderly patients with moderate to severe MR not amenable to surgery. PMID- 22078426 TI - Transcatheter valve-in-valve implantation for failed surgical bioprosthetic valves. AB - When bioprosthetic cardiac valves fail, reoperative valve replacement carries a higher risk of morbidity and mortality compared with initial valve replacement. Transcatheter heart valve implantation may be a viable alternative to surgical aortic valve replacement for high-risk patients with native aortic stenosis, and valve-in-valve (V-in-V) implantation has been successfully performed for failed surgical bioprostheses in the aortic, mitral, pulmonic, and tricuspid positions. Despite some core similarities to transcatheter therapy of native valve disease, V-in-V therapy poses unique clinical and anatomic challenges. In this paper, we review the challenges, selection criteria, techniques, and outcomes of V-in-V implantation. PMID- 22078427 TI - Clinical outcomes in patients undergoing percutaneous closure of periprosthetic paravalvular leaks. AB - OBJECTIVES: The purpose of this study was to evaluate the feasibility and efficacy of the percutaneous device closure of a consecutive series of patients with periprosthetic paravalvular leaks referred to our structural heart disease center with congestive heart failure and hemolytic anemia. BACKGROUND: Clinically significant periprosthetic paravalvular leak is an uncommon but serious complication after surgical valve replacement. Percutaneous closure has been utilized as an alternative to surgical repair of this defect in high-risk surgical patients. METHODS: This is a retrospective review of 57 percutaneous paravalvular leak closures that were performed in 43 patients (67% male, mean age 69.4 +/- 11.7 years) between April 2006 and September 2010. Integrated imaging modalities were used for the evaluation, planning, and guidance of the interventions. RESULTS: Closure was successful in 86% of leaks and in 86% of patients. Twenty-eight of 35 patients improved by at least 1 New York Heart Association functional class. The percentage of patients requiring blood transfusions and/or erythropoietin injections post-procedure decreased from 56% to 5%. Clinical success was achieved in 89% of the patients in whom procedure was successful. The survival rates for patients at 6, 12, and 18 months after paravalvular leak closures were 91.9%, 89.2%, and 86.5%, respectively. Freedom from cardiac-related death at 42 months post-procedure was 91.9%. CONCLUSIONS: Percutaneous closure of symptomatic paravalvular leaks, facilitated by integrated imaging modalities has a high rate of acute and long-term success and appears to be effective in managing symptoms of heart failure and hemolytic anemia. PMID- 22078428 TI - Long-term follow-up of percutaneous repair of paravalvular prosthetic regurgitation. AB - OBJECTIVES: The goal of this study was to determine the long-term clinical efficacy of percutaneous repair of paravalvular prosthetic regurgitation. BACKGROUND: Percutaneous repair has emerged as an effective therapy for patients with paravalvular prosthetic regurgitation. METHODS: We retrospectively identified 126 patients who underwent catheter-based treatment of symptomatic prosthetic paravalvular regurgitation. Patients were contacted for symptoms, clinical events, and vital status. RESULTS: The 3-year estimate for survival was 64.3% (95% confidence interval: 52.1% to 76.8%). Mortality occurred due to cardiac, noncardiac, and unknown causes in 9.5%, 7.1%, and 5.6% of patients, respectively. Among survivors, 72% of patients who had presented with heart failure were free of severe symptoms and need for cardiac surgery. Severity of residual regurgitation was not related to overall survival but was an important determinant of other clinical events. For those with no, mild, or moderate or severe residual regurgitation, 3-year estimate of survival free of death or need for surgery was 63.3%, 58.3%, and 30.3% (p = 0.01), respectively. CONCLUSIONS: Percutaneous repair of paravalvular prosthetic regurgitation can lead to durable symptom relief in selected patients. Nonetheless, mortality remains significant in symptomatic patients with paravalvular prosthetic regurgitation. Long-term clinical efficacy is highly dependent on residual regurgitation. PMID- 22078430 TI - Wrinkles in the atrium: age, atrial fibrillation, or something else. PMID- 22078429 TI - Structural abnormalities in atrial walls are associated with presence and persistency of atrial fibrillation but not with age. AB - OBJECTIVES: The purpose of this study was to assess the association between structural changes in human atria, age, and history of atrial fibrillation (AF). BACKGROUND: Development of fibrosis in atrial walls is associated with deterioration of atrial conduction and predisposes to AF in experiment. Human data, however, are scarce, and whether fibrosis is a cause or consequence of AF is not known. METHODS: Medical records for consecutive autopsies were checked for AF history and duration. Atrial specimens from 30 patients (ages 64 +/- 12 years) were collected in 3 equal age-matched groups as patients without AF history, with paroxysmal AF, or with permanent AF. Tissue samples were obtained at the level of superior pulmonary veins, inferior pulmonary veins, center of posterior left atrial wall, terminal crest, and Bachmann's bundle. Histology sections were assessed for extent of fibrosis, fatty tissues, and inflammatory infiltration at each location. RESULTS: No correlation was observed between age and fibrosis at any location. Fibrosis extent and fatty infiltration were twofold to threefold higher at all locations in patients with history of AF and correlated with lymphomononuclear infiltration. Patients with permanent AF had greater fibrosis extent than did patients with paroxysmal AF. CONCLUSIONS: In post-mortem material, structural changes in the atria were not associated with age, but were significantly correlated with presence of AF and its severity. Our findings suggest that age-related changes per se are unlikely to be the sole cause of advanced fibrosis underlying AF. PMID- 22078431 TI - Transcatheter patch occlusion of the left atrial appendage using surgical adhesives in high-risk patients with atrial fibrillation. AB - OBJECTIVES: The efficacy of left atrial appendage (LAA) occlusion using the Transcatheter Patch (TP) (Custom Medical Devices, Athens, Greece) in conjunction with surgical adhesives was assessed. BACKGROUND: The TP is a bioabsorbable device that can be adjusted for the shape and size of the LAA without the risk of perforation. It is attached by a surgical adhesive and is released in 45 min. METHODS: Occlusion of the LAA was performed in 20 high-risk patients, 59 to 89 years of age, with atrial fibrillation. A 2-stage polyethylene glycol surgical adhesive was applied to the distal half of the device. Activation of the adhesive was achieved by direct injection of alkaline solution. Fluoroscopy and transesophageal echocardiography only were used for device placement in 17 patients. In 3 patients, angiography was used as well. Follow-up transesophageal echocardiography was performed upon discharge. RESULTS: The procedure was successful in 17 cases. In the 3 patients in whom angiography was performed, the patch did not attach and was retrieved. In 1 case, the patch was placed beyond the mouth of the appendage, resulting in a residual opening. There was further improvement of the occlusion rate on the follow-up transesophageal echocardiography. There was 1 complication related to the procedure, namely, thrombus was released from the long sheath in the left atrium upon withdrawal and required treatment to be dissolved. No recurrent strokes were reported. CONCLUSIONS: Occlusion of the LAA by the TP is feasible and effective in most patients with atrial fibrillation at high risk for embolic stroke. Angiography before placement probably affects patch adhesion and is contraindicated. PMID- 22078432 TI - Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. AB - Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies. CHD birth prevalence worldwide and over time is suggested to vary; however, a complete overview is missing. This systematic review included 114 papers, comprising a total study population of 24,091,867 live births with CHD identified in 164,396 individuals. Birth prevalence of total CHD and the 8 most common subtypes were pooled in 5-year time periods since 1930 and in continent and income groups since 1970 using the inverse variance method. Reported total CHD birth prevalence increased substantially over time, from 0.6 per 1,000 live births (95% confidence interval [CI]: 0.4 to 0.8) in 1930 to 1934 to 9.1 per 1,000 live births (95% CI: 9.0 to 9.2) after 1995. Over the last 15 years, stabilization occurred, corresponding to 1.35 million newborns with CHD every year. Significant geographical differences were found. Asia reported the highest CHD birth prevalence, with 9.3 per 1,000 live births (95% CI: 8.9 to 9.7), with relatively more pulmonary outflow obstructions and fewer left ventricular outflow tract obstructions. Reported total CHD birth prevalence in Europe was significantly higher than in North America (8.2 per 1,000 live births [95% CI: 8.1 to 8.3] vs. 6.9 per 1,000 live births [95% CI: 6.7 to 7.1]; p < 0.001). Access to health care is still limited in many parts of the world, as are diagnostic facilities, probably accounting for differences in reported birth prevalence between high- and low-income countries. Observed differences may also be of genetic, environmental, socioeconomical, or ethnic origin, and there needs to be further investigation to tailor the management of this global health problem. PMID- 22078433 TI - Percutaneous implantation of the Edwards SAPIEN transcatheter heart valve for conduit failure in the pulmonary position: early phase 1 results from an international multicenter clinical trial. AB - OBJECTIVES: The purpose of this study was to evaluate the safety and effectiveness of the Edwards SAPIEN transcatheter heart valve (Edwards Lifesciences LLC, Irvine, California) in the pulmonary position in patients with moderate to severe pulmonary regurgitation with or without stenosis. BACKGROUND: Transcatheter pulmonary valve replacement is evolving, but to date, experience has been limited to the Melody valve (Medtronic Inc., Minneapolis, Minnesota). METHODS: Eligible patients with dysfunctional right ventricle-to-pulmonary artery conduits were screened if body weight was >=35 kg and the in situ conduit diameter was >=16 mm and <=24 mm. Standardized implantation and follow-up protocols were used. RESULTS: Thirty-six patients from 4 centers were recruited between April 2008 and May 2010. Mean body weight was 73.4 +/- 22.9 kg. Successful valve deployment was achieved in 33 of 34 attempts (97.1%). Valve migration occurred in 3 patients, with 2 requiring surgical retrieval; however, 1 patient underwent successful perventricular valve implantation. Further intraprocedure complications included pulmonary hemorrhage (n = 2), ventricular fibrillation (n = 1), and stent migration (n = 1). Pullback gradient across the conduit decreased from 26.8 +/- 18.4 mm Hg to 11.7 +/- 8.0 mm Hg (p < 0.001). The right ventricular/aortic pressure ratio decreased from 0.6 +/- 0.2 to 0.4 +/- 0.1 (p < 0.001). Peak Doppler gradient across the right ventricular outflow tract decreased from 41.9 +/- 27.9 mm Hg to 19.1 +/- 13.3 mm Hg (p < 0.001). At 6-month follow-up, all patients were alive. The number of patients with New York Heart Association functional class I increased from 5 at baseline to 27 at follow-up. Pulmonary regurgitation was <=2+ in 97% of patients. Freedom from reintervention was 97% with 1 patient undergoing elective placement of a second valve due to conduit-induced distortion of the initial implant. CONCLUSIONS: Transcatheter pulmonary valve replacement using the Edwards SAPIEN transcatheter heart valve is safe and effective in patients with dysfunctional right ventricle-to-pulmonary artery conduits. PMID- 22078434 TI - Permanent right-to-left shunt is the key factor in managing patent foramen ovale. AB - OBJECTIVES: We sought to prospectively evaluate risk of stroke and impact of transcatheter patent foramen ovale (PFO) closure in patients with permanent right to left shunt compared with those with Valsalva maneuver-induced right-to-left shunt. BACKGROUND: Pathophysiology and properly management of PFO still remain far from being fully clarified: in particular, the contribution of permanent right-to-left shunt remains unknown. METHODS: Between March 2006 and October 2010, we enrolled 180 (mean age 44 +/- 10.9 years, 98 women) of 320 consecutive patients referred to our center for transcatheter PFO closure, who had spontaneous permanent right-to-left shunt on transcranial Doppler and transthoracic/transesophageal echocardiography. All patients fulfilled the standard current indications for transcatheter closure and underwent preoperative transesophageal echocardiography and brain magnetic resonance imaging, with subsequent intracardiac echocardiographic-guided transcatheter PFO closure. We compared the clinical echocardiographic characteristics of these patients (Permanent Group) with the rest of 140 patients with right-to-left shunt only during Valsalva maneuver (Valsalva Group). RESULTS: Compared with the Valsalva Group patients, patients of the Permanent Group had increased frequency of multiple ischemic brain lesions on magnetic resonance imaging, previous recurrent stroke, previous peripheral arteries embolism, migraine with aura, and-more frequently-atrial septal aneurysm and prominent Eustachian valve. The presence of permanent shunt confers the highest risk of recurrent stroke (odds ratio: 5.9, 95% confidence interval: 2.0 to 12, p < 0.001). No differences were recorded between the 2 groups with regard to recurrence of ischemic events after the closure procedure. CONCLUSIONS: Despite its small-sample nature, our study suggests that patients with permanent right-to-left shunt have potentially a higher risk of paradoxical embolism compared with those without. PMID- 22078435 TI - SIGNATURE: a workbench for gene expression signature analysis. AB - BACKGROUND: The biological phenotype of a cell, such as a characteristic visual image or behavior, reflects activities derived from the expression of collections of genes. As such, an ability to measure the expression of these genes provides an opportunity to develop more precise and varied sets of phenotypes. However, to use this approach requires computational methods that are difficult to implement and apply, and thus there is a critical need for intelligent software tools that can reduce the technical burden of the analysis. Tools for gene expression analyses are unusually difficult to implement in a user-friendly way because their application requires a combination of biological data curation, statistical computational methods, and database expertise. RESULTS: We have developed SIGNATURE, a web-based resource that simplifies gene expression signature analysis by providing software, data, and protocols to perform the analysis successfully. This resource uses bayesian methods for processing gene expression data coupled with a curated database of gene expression signatures, all carried out within a GenePattern web interface for easy use and access. CONCLUSIONS: SIGNATURE is available for public use at http://genepattern.genome.duke.edu/signature/. PMID- 22078436 TI - Hyperalgesia by synaptic long-term potentiation (LTP): an update. AB - Long-term potentiation of synaptic strength (LTP) in nociceptive pathways shares principle features with hyperalgesia including induction protocols, pharmacological profile, neuronal and glial cell types involved and means for prevention. LTP at synapses of nociceptive nerve fibres constitutes a contemporary cellular model for pain amplification following trauma, inflammation, nerve injury or withdrawal from opioids. It provides a novel target for pain therapy. This review summarizes recent progress which has been made in unravelling the properties and functions of LTP in the nociceptive system and in identifying means for its prevention and reversal. PMID- 22078437 TI - Obesity and pulmonary embolism: the mounting evidence of risk and the mortality paradox. AB - PURPOSE: To determine the prevalence of pulmonary embolism in obese patients according to age, gender and comorbid conditions and explore the relation of obesity to mortality. METHODS: The number of patients discharged from short-stay hospitals throughout the United States from 1998-2008 with pulmonary embolism who were obese or not obese, and in-hospital all-cause mortality were determined from the Nationwide Inpatient Sample. RESULTS: From 1998-2008, 203,500 of 17,979,200 (1.1%) obese patients were diagnosed with pulmonary embolism compared with 2,034,100 of 346,049,800 (0.6%) non-obese patients [relative risk (RR) =2.03]. Relative risk for pulmonary embolism was highest among obese patients aged 11-20 years (RR=5.80) and was higher in obese women (RR=2.08) than in obese men (RR=1.74). Mortality was 4.3% in obese patients with pulmonary embolism compared with 9.5% in non-obese patients (RR=0.45). Obesity had the greatest effect on mortality in older patients and little effect in teenagers and young adults. Among stable patients who did not receive thrombolytic therapy, mortality was 3.8% in obese patients and 8.4% in non-obese patients (RR=0.45). Among unstable patients, obesity had little effect on mortality. CONCLUSIONS: The prevalence of pulmonary embolism in hospitalized patients was higher in obese patients than in non-obese patients. Mortality in patients with pulmonary embolism was lower in obese patients than in non-obese patients, with the greatest effects in women, older patients and stable patients. PMID- 22078438 TI - [Intranasal vaccination with mycobacterial 65-kD heat-shock protein can prevent insulitis and diabetes in non-obese diabetic mice]. AB - AIM: To study the efficacy of heat shock protein 65 kDa (HSP65) of Mybobacterium tuberculosis var. bovis in prevention of autoimmune diabetes by intranasal. METHODS: The HSP65 gene was derived from Mybobacterium tuberculosis var. bovis genome by PCR and successfully expressed as soluble protein in Escherichia coli. The recombinant protein HSP65 was purified by anion exchange column chromatography, then used to immunize prediabetic NOD (non-obese diabetic) mice via three intranasal (i.n.) delivery in absence of adjuvants. Serum samples from the immunized mice were collected at monthly intervals. The anti-HSP65 antibody was detected by enzyme-linked immunosorbent assay (ELISA) and verified by Western blot analysis. The concentration of blood glucose was measured by automatic analyzer. RESULTS: Specific anti-HSP65 antibodies were successfully induced in mice immunized via intranasal routes. Histochemical analysis of mice pancreas tissue showed that HSP65 intranasal vaccination could decrease pathological changes in NOD mice. CONCLUSION: Intranasal vaccination with HSP65 in NOD mice could prevent the development of diabetes. Our results demonstrate that intranasal vaccination with HSP65 reduces significantly the inflammatory process associated with auto-immune diabetes. This approach may offer novel therapeutic avenues for the treatment for of type 1 diabetes mellitus. PMID- 22078439 TI - [Prokaryotic expression and immunogenicity analysis of the chimeric HBcAg containing APP beta cleavage site peptide and Abeta(1-15);]. AB - AIM: To construct the recombinant prokaryotic expression plasmid pET/c-ABCSP Abeta(15-c);, and evaluate the immunogenicity of the fusion protein expressed in E.coli. METHODS: The gene fragment HBc88-144 was amplified by PCR and subcloned to pUC19. The APP beta cleavage site peptide(ABCSP) and Abeta(1-15); gene(ABCSP-Abeta(15);) was amplified by PCR and inserted downstream of HBc1-71 in pGEMEX/c1-71. After restriction enzyme digestion, c1-17-ABCSP-Abeta(15); were connected with HBc88-144, yielding the recombinant gene c-ABCSP-Abeta(15-c);. c ABCSP-Abeta(15-c); gene was subcloned into pET-28a(+).The fusion protein expressed in transformed E.coli BL21 was induced with IPTG and analyzed by SDS PAGE. The virus-like particles (VLP) formed by fusion protein was observed with Transmission Electron Microscope (TEM). 4 Kunming (KM) mice received intraperitoneal injection (i.p) of fusion protein VLP. The antibody was detected by indirect ELISA. RESULTS: The recombinant gene was confirmed by restriction enzyme digestion and DNA sequencing. After IPTG induction, fusion protein was expressed and mainly existed in the sediment of the bacterial lysate. The expression level was 40% of all the proteins in the sediment. The fusion protein could form VLP. After 5 times of immunization, the titer of anti-ABCSP and anti Abetaantibody in sera of KM mice reached up to 1:5 000 and 1:10 000 respectively, while the anti-HBc antibody was undetectable. CONCLUSION: Recombinant c-ABCSP Abeta(15-c); gene can be expressed in E.coli. The expressed protein could form VLP and has a strong immunogenicity. This study lays the foundation for the study of AD genetic engineering vaccine. PMID- 22078440 TI - [Synthesis and identification of artificial complete antigen 25-hydroxyvitamin D(3);]. AB - AIM: To synthesize the 25-hydroxyvitamin D(3); artificial complete antigen and to prepare the specific antibody against 25-hydroxyvitamin D(3);. METHODS: The active group carboxyl was introduced into 25-hydroxyvitamin D(3); and formed 25 hydroxyvitamin D(3);-hemisuccinate which possessed the structure of the hapten by chemical modification. The EDC method was applied to conjugate 25-hydroxyvitamin D(3);-hemisuccinate to bovine serum albumin as an artificial immunogen. The coating antigen 25-hydroxyvitamin D(3);-hemisuccinate-OVA was obtained in the same way. Ultraviolet, SDS-PAGE and MALDI-TOF were used to identify 25 hydroxyvitamin D(3);-hemisuccinate-BSA. RESULTS: BALB/c mice were immunized with 25-hydroxyvitamin D(3);-hemisuccinate-BSA to generate the polyclonal antibody of the 25-hydroxyvitamin D(3); worth high titer and the immunogen, 25 hydroxyvitamin D(3);-hemisuccinate-BSA, was successfully prepared with coupling ratio (12+/-0.16):1(N=3) coupling. CONCLUSION: The high titer and good sensitivity of anti-25-hydroxyvitamin D(3); antibody are produced in sera immunized BALB/c mice, which made it possible to develop a clinical diagnostics for illness. PMID- 22078441 TI - [Identification and expression analysis of a novel splice variant of human tumor necrosis factor receptor associated factor 2]. AB - AIM: Identification of a novel splice variant of tumor necrosis factor receptor associated factor 2 and its expression analysis. METHODS: By PCR analysis, we identified the existence of a new splice variant of TRAF2 using human brain cDNA library as template. RNA isolated from various cell lines and tissues was subjected to RT-PCR and differential expression analysis of TRAF2 splice variants was carried out. RESULTS: An amplification of about 1 500 bp was found using P1 and P2 as the primers. we performed PCR using exon 6 flanking primers P3 and P4, yielding a full-length transcript of 268 bp (including exon 6) and a novel splice variant of 193 bp lacking the 75 bp of exon 6. The full-length transcript of TRAF2 was found to be dominant in T47D, glioma of grade II and grade III. However the novel splice lacking exon 6 was dominant in Hep3B, GC-1, MCF7, fetus brain and glioma of grade I, the two splices of TRAF2 were similar in PANCI, Hek293 and SW480.We couldn't find any expression of TRAF2 in HepG2, HBL100, A549 and HeLa . CONCLUSION: TRAF2 has a novel splice lacking 6 exon in human beside the full-length splice. The two splices are differential expression in tissues and cell lines. PMID- 22078442 TI - [The study of anti-tumor activities of DC vaccine loaded with multi-epotipes of survivin]. AB - AIM: To observe the anti-tumor activity of dendritic cell (DC)vaccine loaded with multi-epitopes of survivin. METHODS: The recombinant plasmid pPIRESneo3.0 survivin (4)/Th which include four survivin HLA-A2-restricted CD8(+); CTL epitopes and a CD4(+);Th epitope, pPIRESneo3.0-survivin (4) which include four survivin CD8(+); CTL epitopes, were transfected into human dendritic cells respectively. There were five groups, which included survivin(4)/Th group, survivin(4)group, empty plasmid group, untransfected group and T lymphocytes group The expression of CD83 and CD86 on the surface of DCs, the expression of CD4 and CD8a on the surface of T lymphocytes, the apoptotic rates of MCF-7 cells after treated by DC vaccine were measured by flow cytometry; IFN-gamma levels of all groups were detected by ELISA and the growth inhibition of MCF-7 cells after being treated with DC vaccine was tested by MTT colorimetry. RESULTS: The results of flow cytometry revealed that high levels CD83 and CD86 were expressed on the surface of DCs; high levels CD4 and CD8a were expressed on the surface of T lymphocytes; the IFN-gamma levels in survivin(4)/Th group [(66.50+/ 3.34)ng/L]were significantly higher than that in survivin(4)group[(46.10+/ 1.35)ng/L], empty plasmid group[(25.17+/-0.32)ng/L], untransfected group [(25.47+/-0.95)ng/L] or T lymphocytes group[(23.73+/-0.50)ng/L](P<0.05). The inhibition rate of MCF-7 cells in survivin(4)/Th group was significantly higher than that in survivin(4)group, empty plasmid group, untransfected group or T lymphocytes group(P<0.05). The apoptotic rate of MCF-7 cells in survivin(4)/Th group was (10.63+/-0.29)% after treated by DC vaccine, which was significantly higher than that in in survivin(4)group, empty plasmid group, untransfected group or T lymphocytes group(P<0.05). CONCLUSION: The DCs vaccine loaded with multi- CD8(+); CTL epitopes of survivin has strong anti-tumor effects. CD4(+); Th cells can promote the anti-tumor activity of CD8(+);CTL. PMID- 22078443 TI - [Construction of recombinant shuttle plasmid pIMP1-eHER2/neu and screening and identification of its stable Clostridium sporogenes transformants]. AB - AIM: To construct recombinant clostridium sporogenes modified with the extracellular domain of human oncogene HER2/neu, to lay a foundation for further study of its antitumor effect. METHODS: The extracellular domain (ECD) of HER2/neu gene was attached to the downstream of promoter and signal sequence of clostridia endo-1, 4-glucanase (eglAp) by SOE-PCR to construct fusion gene eglAp HER2/neu, which was then inserted into E.coli-clostridia shuttle plasmid pIMP1 to construct recombinant plasmid pIMP1-eHER2/neu. The recombinant plasmid was firstly transformed into E.coli DH5alpha.Then the correct construct was identified and introduced into C. sporogenes by electroporation. Positive clones were selected by erythromycin resistance, bacteria PCR were used for verification. RESULTS: Restriction map and sequencing result showed that the sequence and ORF of fusion gene eglAp-HER2/neu in recombinant plasmid pIMP1 eHER2/neu was correct. Bacteria PCR results indicated that the recombinant plasmid pIMP1-eHER2/neu was successfully transformed into C.sporogenes. After more than 20 passages under antibiotic pressure, C.sporogenes transformants could stably carry the recombinant plasmid pIMP1-eHER2/neu. CONCLUSION: Stable C.sporogenes transformants with the recombinant plasmid pIMP1-eHER2/neu are successfully acquired, which laid a foundation for further anti-tumor study. PMID- 22078445 TI - [The Enhanceing effect of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils in tuberculosis patients]. AB - AIM: To explore the effects of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils or polymorphonuclear cells (PMNs) in tuberculosis patients. METHODS: The fresh peripheral blood samples from TB patients and healthy adults were incubated with M.tb labeled with FITC, and the percentages of phagocytosis of M.tb by PMNs was measured by flow cytometry (FCM). The fresh peripheral blood samples were incubated with DCFH-DA, and with or without M.tb for different times, the percentage of activation and the ROS production of PMNs were measured by FCM. Whole blood samples were pretreated with IL-12, the changes of phagocytosis, activation and ROS production of PMNs were measured by FCM. RESULTS: The percentages of phagocytosis by PMNs, activation and ROS production of PMNs in both TB patients and healthy adults increased dependent on the time of incubation with M.tb. Only the phagocytosis of M.tb by PMNs at 5 min in TB patients of tuberculosis patients (51.82+/-6.93)% was obviously higher than that in healthy adults (47.20+/-4.26)%, (P<0.05). Pretreatment of whole blood with IL-12 before incubation with M.tb, the percentages of phagocytosis, activation and ROS production of PMNs in both TB patients and healthy adults increased in dose dependent manner, but no significant difference was found between both groups. CONCLUSION: The results indicated that the phagocytosis of M.tb and ROS production by PMNs in TB patients were almost the same as that in healthy controls, except for phagocytosis is higher at early stage. Furthermore, IL-12 can enhance the responsiveness to the phagocytosis and ROS production of PMNs. PMID- 22078444 TI - [Mechanism of ING4 mediated inhibition of the proliferation and migration of human glioma cell line U251]. AB - AIM: To investigate the effect of Ad-ING4 on proliferation and migration of glioma cells and explore its probable mechanism. METHODS: U251 were infected with Ad-ING4. ING4 gene expression was evaluated by RT-PCR. MTT assay was adopted to evaluate the effect of ING4 on proliferation of U251; Boyden chamber assay was used to check the effect of ING4 on the migration of U251. In ING4 transfected U251, Western blot was used for detecting NGF and TrkA expression; Pull-down assay was used for detecting active RhoA expression. RESULTS: ING4 was overexpressed in Ad-ING4 transfected U251 cells. ING4 inhibited proliferation and migration of U251 significantly. Moreover, overexpression of ING4 result in depression of NGF, TrkA and active RhoA. CONCLUSION: ING4 mediated inhibition of the proliferation and migration of human glioma cells by down regulating NGF, TrkA and active RhoA expression. PMID- 22078446 TI - [Study on macrophages infected with Mycobacterium tuberculosis H37Ra in vitro]. AB - AIM: To study the production of nitric oxide and secretion of cytokines after infection of macrophages with Mycobacterium tuberculosis H37Ra. METHODS: 24 hours after infection of RAW264.7 cells with Mycobacterium tuberculosis H37Ra, the production of NO and H(2);O(2); as well as the secretion levels of IL-12 and TNF alpha in the supernatants of culture were determined by Griess method, chemical method and ELISA assay respectively. The expression of IL-12 and TNF-alpha mRNA in macrophages was detected by reverse transcription polymerase chain reaction (RT- PCR). RESULTS: Macrophages infected with Mycobacterium tuberculosis H37Ra produced effectively more NO, H(2);O(2);, and enhanced the release of IL-12, TNF-alpha and the expression of IL-12, TNF-alpha mRNA (P<0.05). CONCLUSION: Mycobacterium tuberculosis H37Ra can induce the production of more nitric oxide and cytokines which play important roles in the host immune response. PMID- 22078447 TI - [Effect of the ethanol extracts of starfish Asterias amurensis on the levels of serum IL-4 and IFN-gamma in mice]. AB - AIM: To investigate the effect of the ethanol extracts of the starfish Asterias amurensis on the levels of serum IL-4 and IFN-gamma in mice. METHODS: The whole bodies of the starfish were chopped and extracted with ethanol. The ethanol extracts were chromatographed on silica gel column. The separating fractions of the ethanol extracts were intraperitoneally injected into mice, respectively. The levels of serum IL-4 and IFN-gamma in mice were detected by ELISA. RESULTS: The ethanol extracts from the starfish were separated through silica gel column chromatography to obtain 8 fractions (I-VIII). The high levels of IL-4 and IFN gamma were produced in serum of the mice injected with fractions III and VIII of the ethanol extracts from the starfish Asterias amurensis. CONCLUSION: The fractions III and VIIII separated from the ethanol extracts of the starfish Asterias amurensis can stimulate the mice to produce high lelves of IL-4 and IFN gamma, which has the characteristic of natural kill T (NKT) cells activator. It is suggests that there is the active substance that can activate NKT cells in the starfish Asterias amurensis. PMID- 22078448 TI - [Construction and expression of human anti-HER2 scFv-9R fusion protein and identification of its activity]. AB - AIM: To construct, express and purify a human fusion protein, which is composed of a single-chain antibody fragment scFv that recognizes HER2 protein and an oligo-9-arginine, and to analyze the binding activity of the expressed fusion protein. METHODS: Pairs of oligonucleotide primers were designed and used to amplify the scFv-9R. The fusion protein gene scFv-9R was then cloned into expression vector pQE30 and expressed in E.coli M15.Expressed protein was detected by SDS-PAGE and Western blot and purified by Ni-NTA chelating agarose. Then, the purified protein was refolded by dialysis and concentrated by ultrafiltration. The antigen-binding activity of the scFv-9R fusion protein was confirmed by ELISA, and the siRNA binding ability was confirmed by electrophoretic mobility shift assay (EMSA). RESULTS: HER2 scFv-9R encoding sequence was correctly cloned into the expression vector. The recombinant protein was insolubly expressed in E.coli M15 induced by IPTG. ELISA confirmed that it had specific antigen binding activity; EMSA assured that it had siRNA binding activity. CONCLUSION: The scFv-9R fusion protein can specially bind with both HER2 antigen and siRNA. PMID- 22078449 TI - [Preparation and characterization of monoclonal antibodies specific for CjaA protein of Campylobacter jejuni]. AB - AIM: Expression, purification of Campylobacter jejuni CjaA protein and development of monoclonal antibodies (mAbs) against this protein. METHODS: The C. jejuni cjaA gene was amplified and inserted into the expression plasmids, pGEX 6p-1 and pET30a (+). The purified rGST-CjaA protein was used as an immunogen in 8 week-old BALB/c mice, and injected subcutaneously. The purified rHis-CjaA protein used as a detecting antigen for screening mAbs against CjaA was prepared. The specificity of mAbs was characterized by Dot-ELISA and Western blot assays. RESULTS: The recombinant expression plasmids, pGEX-6p-1-cjaA and pET30a(+)-cjaA were obtained. The sizes of the recombinant proteins, rGST-CjaA and rHis-CjaA, were consistent with their predicted size. Specific reaction was found between CjaA positive serum and expressed protein by Western blot assay, confirming its identification as a Campylobacter jejuni immunogen. Three hybridoma cell lines, designated 2B6, 3C2 and 4F11, secreting mAbs against CjaA were obtained. Their immunoglobulin subclasses were all IgG1. The ELISA titers of the ascites fluid were 1:1*10(5);, 1:2*10(5); and 1:4*10(5);, respectively. Western blot analysis confirmed that the three mAbs reacted with the rHis-CjaA fusion protein but not the His tag. The Dot-ELISA results demonstrated that the three mAbs only with CjaA and not the tags for the expression vectors. CONCLUSION: The successful preparation of three mAbs specific for the CjaA protein lays the foundation for further study regarding the biological characteristics of CjaA and the pathogenesis of C. jejuni. PMID- 22078450 TI - [Preparation and characterization of three novel monoclonal antibodies against human PD-L1]. AB - AIM: To prepare a functional mouse anti-human PD-L1 monoclonal antibody and to characterize its biological activities. METHODS: A stable human PD-L1 transfected cell line L929/PD-L1 was used as an antigen to immunize BALB/c mice. By means of the cell fusion technique, multiple cell subcloning, repeated screening with L929/ PD-L1 as target cells and the L929/mock cells used as the negative control, the hybridomas specifically secreting mouse anti-PD-L1 monoclonal antibodies were generated. Then its biological characterization was investigated by rapid murine Ig-subclass typing, Western blotting, indirect immune of luorescene assay, mutual competitive inhibition test. By means of MTT incorporation assay, detected the infection of mAb to T cell proliferation. Three mouse anti-human PD-L1 monoclonal antibodies were generated, named as 11G8, 2G5 and 5C3. RESULTS: The results of characterization study showed that the monoclonal antibodies could recognize the PD-L1 on the activated T cells. The mAbs could promote T cells proliferation. CONCLUSION: It is evident that the functional monoclonal antibodies for human PD L1 have been generated, and it would provide the initial material for further study on the role of PD-1/PD-L1 signaling pathways. PMID- 22078451 TI - [Primary detection of biological functions of anti-hGITR(aa27-165);PcAb]. AB - AIM: To detect the rabbit-derived polyclonal antibodies against extracellular protein segments of human glucocorticoid-inducible tumor necrosis factor receptors (anti-hGITR(aa27-165);PcAb) with regard to its capacity of linkage to natural GITR molecules and the function on CD4(+); T cells. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated and cultured under stimulation; flow cytometry was applied to check the capacity of anti-hGITR(aa27 165);PcAb for linkage to natural GITR molecules on PBMCs; human CD4(+); T cells were isolated by immunological magnetic beads and (3);H-TdR incorporation tests were performed to observe improving-proliferation action of anti-hGITR(aa27 165);PcAb while CD4(+); T cells were cultured with or not with some cytokines. RESULTS: Anti-hGITR(aa27-165);PcAb was able to bind GITR molecules with natural conformation in a concentration-dependent way; furthermore, this PcAb could improve the reproduction of CD4(+); T cells. CONCLUSION: The rabbit-derived anti hGITR(aa27-165);PcAb prepared in our laboratory is capable of linking to natural target molecules and possesses the activation function upon CD4(+); T cells, the further exploration should allow for its applications for diagnosis and treatment of relavent diseases. PMID- 22078452 TI - [Association between polymorphisms of interleukin-6 gene promoter and breast cancer]. AB - AIM: To study possible association between three single nucleotide polymorphisms (-597G/A, -572C/G and -174G/C) of interleukin-6 (IL-6) gene promoter and breast cancer. METHODS: Genomic DNA was isolated from the venous blood leukocytes from 176 unrelated patients with breast cancer and 200 healthy unrelated females (control group). Polymorphisms of -597G/A, -572C/G and -174G/C, were genotyped by PCR-restriction fragment length polymorphisms (PCR-RFLP). SPSS 11.5 software was employed for statistical analysis and the association of IL-6 polymorphisms with breast cancer was evaluated by x(2); test. RESULTS: There was significant differences in both allele and genotype frequencies of -572C/G in case group compared with control group. The allele G of -572C/G was significantly higher in cancer patients than the controls(x(2);=15.438, P<0.01). CONCLUSION: There is an association between -572C/G polymorphism and breast cancer risk. The females with G allele of -572C/G are susceptible to breast cancer compared with non-carrying females. PMID- 22078453 TI - [Study on functions and mechanism of curcumin in inducing gastric carcinoma BGC apoptosis]. AB - AIM: discuss the biological function and regulation mechanism of curcumin in promoting human gastric carcinoma BGC-823 apoptosis. METHODS: Conventional in virto culture in logarithmic phase gastric carcinoma BGC-823 cells; cells are divided into four groups: control group, low treatment group, middle treatment group and high treatment group, with curcumin concentration being 0 mg/L, 5 mg/L, 10 mg/L, and 20 mg/L, respectively. 24 hours after curcumin is treated, cell proliferation level and apoptosis rate are measured with MTT colorimetry and flow cytometry, Bax, Bcl-2 protein expression is measured with immunohistochemistry; mRNA of Caspase-3 is tested by means of PCR. RESULTS: MTT test indicates that curcumin can inhibit human gastric carcinoma BGC-823 cell proliferation, showing concentration dependency; flow cytometry shows that curcumin can effectively induce apoptosis, showing concentration dependency, where the apoptosis rate is 48.3% 24 hours after 20 mg/L curcumin is treated; immunohistochemistry test shows that curcumin treatment enables Bax expression level in human gastric carcinoma BGC-823 cells to go up, meanwhile, the Bcl-2 protein expression level to go down, besides, the mRNA expression level of Caspase-3 in cells increases through induction of curcumin. CONCLUSION: Curcumin has obvious inhibitory effect on human gastric carcinoma BGC-823 cell proliferation, showing concentration dependency to promote apoptosis. Such biological effect may be associated with activating Caspase-3 signal channel by activating Bax protein expression and inhibiting Bcl-2 protein. This study lays an important foundation for further discussing the mechanism of curcumin in inducing human gastric carcinoma BGC-823 apoptosis. PMID- 22078454 TI - [Expression and clinical significance of Nrf2 in esophageal squamous cell carcinoma]. AB - AIM: To study the expression and clinical significance of Nrf2 (Nuclear factor E2 p45-related factor 2) in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of Nrf2 in 32 cases of EC tissues, 30 cases of adjacent tissues, 21 positive Lymph node tissues and 24 negative Lymph node tissues was assessed by SP immunohistochemical method. RESULTS: The main location of Nrf2 was nuclear, and the positive rates of Nrf2 in the cancer tissues was 78.13%, while that in the adjacent tissues group was 13.33%, and showed 66.67% and 20.83% in the positive Lymph node tissues and negative Lymph node tissues respectively, there was a significant difference between the two groups (P<0.05). The Nrf2 positive rate was closely correlated with the lymph node metastasis (P<0.05), but showed no statistical associated with age, sex, TNM stage, degree of tumor differentiation and the location of tumor. CONCLUSION: The Nrf2 has high expression in ESCC tissues, and the positive rate is closely correlated with the lymph node metastasis, The Nrf2 may play an important role in ESCC oncogenesis and drug resistence. PMID- 22078455 TI - Characterization of a naturally occurring degradation product of the LDL receptor. AB - In this study we have characterized a naturally occurring truncated form of the low density lipoprotein receptor (LDLR). Western blot analysis of transfected cells indicated that the truncated form (?N-LDLR) is a degradation product of the full-length LDLR generated by cleavage in the linker region between ligand binding repeats 4 and 5 of the ligand-binding domain. The cleavage of the linker was not caused by components of the culture media, as heat inactivation of the media did not prevent cleavage. Rather, it is assumed that cleavage was caused by an enzyme secreted from the cells. Biotinylation experiments showed that ?N-LDLR is located on the cell surface and is detectable approximately 5 h after synthesis of the full-length LDLR. Flow cytometric analysis showed that ?N-LDLR was not able to bind and internalize low density lipoprotein (LDL). ?N-LDLR appeared to be equally stable as the full-length LDLR. Thus, generation of ?N LDLR does not appear to be the first signal for degradation of the LDLR. The existence of two functionally different populations of LDLRs on the cell surface, of which ?N-LDLR constitutes 28%, must be taken into account when interpreting results of experiments to study LDLRs on the cell surface. Furthermore, if the cleavage of the linker between ligand-binding repeats 4 and 5 could be prevented by an enzyme inhibitor, this could represent a novel therapeutic strategy to increase the number of functioning LDLRs and thereby decrease the levels of plasma LDL cholesterol. PMID- 22078456 TI - Developing treatment options for metachromatic leukodystrophy. AB - Metachromatic leukodystrophy (MLD) represents a devastating lysosomal storage disease characterized by intralysosomal accumulation of the sphingolipid sulfatide in various tissues. Three types of the disease are currently distinguished: the late-infantile, which is the most commonly observed, the juvenile and the adult type. Demyelination represents the main histopathological feature of the disorder, leading to neurological impairment with no curative treatment currently available. Nevertheless, the increased scientific interest on the disease has led to the experimental use of innovative therapeutic approaches in animal models, aiming to provide an effective therapeutic regimen for human patients, as well. This paper provides an overview of developing treatment options among patients with MLD. Apart from hematopoietic stem cell transplantation, already in use for decades, other recent data discussed includes umbilical cord blood and stem cell transplantation, enzyme replacement therapy, gene therapy and autologous hematopoietic transplantation of genetically modified stem cells. Gene therapy with oligodedroglial, neural progenitor, embryonic and microencapsulated recombinant cells represents add-on treatment options still on experimental level. PMID- 22078457 TI - Neurologic considerations in propionic acidemia. AB - Propionic acidemia (PA) is an organic acidemia which has a broad range of neurological complications, including developmental delay, intellectual disability, structural abnormalities, metabolic stroke-like episodes, seizures, optic neuropathy, and cranial nerve abnormalities. As the PA consensus conference hosted by Children's National Medical Center progressed from January 28 to 30, 2011, it became evident that neurological complications were common and a major component of morbidity, but the role of imaging and the basis for brain pathophysiology were unclear. This paper reviews the hypothesized pathophysiology, presentation and uses the best available evidence to suggest programs for treatment, imaging, and monitoring the neurological complications of PA. PMID- 22078458 TI - Rheological and dielectric properties of different gold nanoparticle sizes. AB - BACKGROUND: Gold nanoparticles (GNPs) have found themselves useful for diagnostic, drug delivery and biomedicine applications, but one of the important concerns is about their safety in clinical applications. Nanoparticle size has been shown to be an extremely important parameter affecting the nanoparticle uptake and cellular internalization. The rheological properties assume to be very important as it affects the pressure drop and hence the pumping power when nano fluids are circulated in a closed loop. The rheological and dielectric properties have not been documented and identified before. The aim of the present study was to investigate the rheology and the dielectric properties of different GNPs sizes in aqueous solution. METHODS: 10, 20 and 50 nm GNPs (Product MKN-Au, CANADA) was used in this study. The rheological parameters were viscosity, torque, shear stress, shear rate, plastic viscosity, yield stress, consistency index, and activation energy. These rheological parameters were measured using Brookfield LVDV-III Programmable rheometer supplied with temperature bath and controlled by a computer. RESULTS: The shear stress and shear rate of GNPs have shown a linear relationship and GNPs exhibited Newtonian behaviour. The GNPs with larger particle size (50 nm) exhibited more viscosity than those with smaller particle sizes (10 and 20 nm). Viscosity decreased with increasing the temperature for all the examined GNP sizes. The flow behaviour index (n) values were nearly <= 1 for all examined GNP sizes. Dielectric data indicated that the GNPs have strong dielectric dispersion in the frequency range of 20-100 kHz. The conductivity and relaxation time decreased with increasing the GNP size. CONCLUSIONS: This study indicates that the GNP size has considerable influence on the viscosity of GNPs. The strong dielectric dispersion was GNP size dependent. The decrease in relaxation time might be attributed to increase in the localized charges distribution within the medium confirmed by the conductivity data. This study suggests that further experiments are required to be done after the administration of GNPs through different routes in rats in vivo. PMID- 22078459 TI - Evaluation of PAN-based manganese dioxide composite for the sorptive removal of cesium-137 from aqueous solutions. AB - Hydrous manganese dioxide-polyacrylonitrile (MnO(2)-PAN) was chemically synthesized and evaluated, as an organic-inorganic composite material, for the removal of radio-contaminant cesium-137 from aqueous solutions. The physico chemical characterization was carried out by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), CHN elemental analysis, scanning electron microscopy (SEM), nitrogen adsorption-desorption studies and thermogravimetry-differential scanning calorimetry (TGA-DSC). Batch experiments were carried out as a function of contact time, interference of the coexisting ions and initial pH of adsorptive solution applying a radiotracer technique. The effect of temperature on the distribution coefficient of cesium has been utilized in order to evaluate the changes in the standard thermodynamic parameters. The results indicated that Cs(+) ions could be efficiently removed using MnO(2)-PAN composite in the pH range of 4-9 from aqueous solutions and the uptake of cesium is affected to varying degrees by the presence of some diverse co-ions. The equilibrium isotherms have been determined and the sorption data were successfully modeled using Freundlich model. PMID- 22078461 TI - Accuracy of MRI findings in chronic lateral ankle ligament injury: comparison with surgical findings. AB - AIM: To evaluate the accuracy of magnetic resonance imaging (MRI) findings in chronic lateral ankle ligament injury in comparison with that of surgical findings. MATERIALS AND METHODS: Forty-eight cases (25 men, 23 women, mean age 36 years) of clinically suspected chronic ankle ligament injury underwent MRI studies and surgery. Sagittal, coronal, and axial, T1-weighted, spin-echo, proton density and T2-weighted, fast spin-echo images with fat saturation were obtained in all patients. MRI examinations were read in consensus by two fellowship trained academic musculoskeletal radiologists who evaluated the lateral ankle ligaments, including the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) without clinical information. The results of the MRI studies were then compared with the surgical findings. RESULTS: The MRI findings of ATFL injury showed a sensitivity of detection of complete tears of 75% and specificity of 86%. The sensitivity of detection of partial tears was 75% and the specificity was 78%. The sensitivity of detection of sprains was 44% and the specificity was 88%. Regarding the MRI findings of CFL injury, the sensitivity of detection of complete tears was 50% and the specificity was 98%. The sensitivity of detection of partial tear was 83% and the specificity was 93%. The sensitivity of detection of sprains was 100% and the specificity was 90%. Regarding the ATFL, the accuracies of detection were 88, 58, 77, and 85% for no injury, sprain, partial tear, and complete tear, respectively, and for the CFL the accuracies of detection were 90, 90, 92, and 96% for no injury, sprain, partial tear, and complete tear, respectively. CONCLUSIONS: The diagnosis of a complete tear of the ATFL on MRI is more sensitive than the diagnosis of a complete tear of the CFL. MRI findings of CFL injury are diagnostically specific but are not sensitive. However, only normal findings and complete tears were statistically significant between ATFL and CFL (p < 0.001). PMID- 22078460 TI - Cataract research using electronic health records. AB - BACKGROUND: The eMERGE (electronic MEdical Records and Genomics) network, funded by the National Human Genome Research Institute, is a national consortium formed to develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic health record (EHR) systems for large-scale, high throughput genetic research. Marshfield Clinic is one of five sites in the eMERGE network and primarily studied: 1) age-related cataract and 2) HDL-cholesterol levels. The purpose of this paper is to describe the approach to electronic evaluation of the epidemiology of cataract using the EHR for a large biobank and to assess previously identified epidemiologic risk factors in cases identified by electronic algorithms. METHODS: Electronic algorithms were used to select individuals with cataracts in the Personalized Medicine Research Project database. These were analyzed for cataract prevalence, age at cataract, and previously identified risk factors. RESULTS: Cataract diagnoses and surgeries, though not type of cataract, were successfully identified using electronic algorithms. Age specific prevalence of both cataract (22% compared to 17.2%) and cataract surgery (11% compared to 5.1%) were higher when compared to the Eye Diseases Prevalence Research Group. The risk factors of age, gender, diabetes, and steroid use were confirmed. CONCLUSIONS: Using electronic health records can be a viable and efficient tool to identify cataracts for research. However, using retrospective data from this source can be confounded by historical limits on data availability, differences in the utilization of healthcare, and changes in exposures over time. PMID- 22078462 TI - Thrombosis and obesity: cellular bases. AB - The prevalence of obesity has dramatically increased during the past two decades. Epidemiological studies suggest that obesity is an independent, modifiable risk factor for coronary heart disease, possibly due, at least in part, to the development of a pro-inflammatory and a pro-thrombotic state in obese subjects. In addition, numerous cohort studies have shown a link between obesity and different types of cancer. Accordingly, the regulation of body weight is becoming a serious concern for public health experts and scientists. Although the mechanisms responsible for these associations are still to be fully elucidated, a key role has been assigned to adipokines, a family of hormones which act as modulators of metabolism or inflammation, secreted by adipocytes. Tissue factor, the major physiological trigger of the blood coagulation cascade in vivo, which plays a central role in atherothrombosis and tumor biology, has also been proposed as one of the key molecules responsible for these associations. PMID- 22078463 TI - Access to safe abortion: building choices for women living with HIV and AIDS. AB - In many areas of the world where HIV prevalence is high, rates of unintended pregnancy and unsafe abortion have also been shown to be high. Of all pregnancies worldwide in 2008, 41% were reported as unintended or unplanned, and approximately 50% of these ended in abortion. Of the estimated 21.6 million unsafe abortions occurring worldwide in 2008 (around one in 10 pregnancies), approximately 21.2 million occurred in developing countries, often due to restrictive abortion laws and leading to an estimated 47,000 maternal deaths and untold numbers of women who will suffer long-term health consequences. Despite this context, little research has focused on decisions about and experiences of women living with HIV with regard to terminating a pregnancy, although this should form part of comprehensive promotion of sexual and reproductive health rights.In this paper, we explore the existing evidence related to global and country-specific barriers to safe abortion for all women, with an emphasis on research gaps around the right of women living with HIV to choose safe abortion services as an option for dealing with unwanted pregnancies. The main focus is on the situation for women living with HIV in Brazil, Namibia and South Africa as examples of three countries with different conditions regarding women's access to safe legal abortions: a very restrictive setting, a setting with several indications for legal abortion but non-implementation of the law, and a rather liberal setting.Similarities and differences are discussed, and we further outline global and country-specific barriers to safe abortion for all women, ending with recommendations for policy makers and researchers. PMID- 22078464 TI - Neural dynamics of saccadic and smooth pursuit eye movement coordination during visual tracking of unpredictably moving targets. AB - How does the brain coordinate saccadic and smooth pursuit eye movements to track objects that move in unpredictable directions and speeds? Saccadic eye movements rapidly foveate peripheral visual or auditory targets, and smooth pursuit eye movements keep the fovea pointed toward an attended moving target. Analyses of tracking data in monkeys and humans reveal systematic deviations from predictions of the simplest model of saccade-pursuit interactions, which would use no interactions other than common target selection and recruitment of shared motoneurons. Instead, saccadic and smooth pursuit movements cooperate to cancel errors of gaze position and velocity, and thus to maximize target visibility through time. How are these two systems coordinated to promote visual localization and identification of moving targets? How are saccades calibrated to correctly foveate a target despite its continued motion during the saccade? The neural model proposed here answers these questions. Modeled interactions encompass motion processing areas MT, MST, FPA, DLPN and NRTP; saccade planning and execution areas FEF, LIP, and SC; the saccadic generator in the brain stem; and the cerebellum. Simulations illustrate the model's ability to functionally explain and quantitatively simulate anatomical, neurophysiological and behavioral data about coordinated saccade-pursuit tracking. PMID- 22078465 TI - CYR61 controls p53 and NF-kappaB expression through PI3K/Akt/mTOR pathways in carboplatin-induced ovarian cancer cells. AB - CYR61 over-expression promotes cell proliferation by inhibiting carboplatin induced apoptosis, decreasing Bax expression, and increasing Bcl-xL, Mcl-1, and Bcl-2. At the same time, down-regulating p53 expression, while up-regulated NF kappaB expression. Additionally, p21 and p53 promoter activities were reduced, while NF-kappaB and Bcl-2 activities increased. In parallel, CYR61-expressing cells, during carboplatin-induced apoptosis, resulted in an increase of Akt phosphorylation, while rapamycin-treated cells were not affected. Carboplatin effectively inhibited the activation of mTOR signaling cascade, which includes mTOR, 4E-BP1, p70S6K, HIF-1alpha, and VEGF. These results provide evidence that CYR61 promotes cell proliferation and inhibits apoptosis. PMID- 22078466 TI - Strategy for improving extracellular lipolytic activities by a novel thermotolerant Staphylococcus sp. strain. AB - BACKGROUND: Extracellular bacterial lipases received much attention for their substrate specificity and their ability to function under extreme environments (pH, temperature...). Many staphylococci produced lipases which were released into the culture medium. Reports of extracellular thermostable lipases from Staphylococcus sp. and active in alkaline conditions are not previously described. RESULTS: This study focused on novel strategies to increase extracellular lipolytic enzyme production by a novel Staphylococcus sp. strain ESW. The microorganism needed neutral or alkaline pH values between 7.0 and 12.0 for growth. For pH values outside this range, cell growth seemed to be significantly inhibited. Staphylococcus sp. culture was able to grow within a wide temperature range (from 30 to 55 degrees C). The presence of oils in the culture medium leaded to improvements in cells growth and lipolytic enzyme activity. On the other hand, although chemical surfactants leaded to an almost complete inhibition of growth and lipolytic enzyme production, their addition along the culture could affect the location of the enzyme. In addition, our results showed that this novel Staphylococcus sp. strain produced biosurfactants simultaneously with lipolytic activity, when soapstock (The main co-product of the vegetable oil refining industry), was used as the sole carbon source. CONCLUSION: A simultaneous biosurfactant and extracellular lipolytic enzymes produced bacterial strain with potential application in soap stock treatment. PMID- 22078467 TI - Tyrosine phosphorylation of cortactin by the FAK-Src complex at focal adhesions regulates cell motility. AB - BACKGROUND: Cell migration plays an important role in many physiological and pathological processes, including immune cell chemotaxis and cancer metastasis. It is a coordinated process that involves dynamic changes in the actin cytoskeleton and its interplay with focal adhesions. At the leading edge of a migrating cell, it is the re-arrangement of actin and its attachment to focal adhesions that generates the driving force necessary for movement. However, the mechanisms involved in the attachment of actin filaments to focal adhesions are still not fully understood. RESULTS: Signaling by the FAK-Src complex plays a crucial role in regulating the formation of protein complexes at focal adhesions to which the actin filaments are attached. Cortactin, an F-actin associated protein and a substrate of Src kinase, was found to interact with FAK through its SH3 domain and the C-terminal proline-rich regions of FAK. We found that the autophosphorylation of Tyr(397) in FAK, which is necessary for FAK activation, was not required for the interaction with cortactin, but was essential for the tyrosine phosphorylation of the associated cortactin. At focal adhesions, cortactin was phosphorylated at tyrosine residues known to be phosphorylated by Src. The tyrosine phosphorylation of cortactin and its ability to associate with the actin cytoskeleton were required in tandem for the regulation of cell motility. Cell motility could be inhibited by truncating the N-terminal F-actin binding domains of cortactin or by blocking tyrosine phosphorylation (Y421/466/475/482F mutation). In addition, the mutant cortactin phosphorylation mimic (Y421/466/475/482E) had a reduced ability to interact with FAK and promoted cell motility. The promotion of cell motility by the cortactin phosphorylation mimic could also be inhibited by truncating its N-terminal F-actin binding domains. CONCLUSIONS: Our results suggest that cortactin acts as a bridging molecule between actin filaments and focal adhesions. The cortactin N-terminus associates with F-actin, while its C-terminus interacts with focal adhesions. The tyrosine phosphorylation of cortactin by the FAK-Src complex modulates its interaction with FAK and increases its turnover at focal adhesions to promote cell motility. PMID- 22078468 TI - Predominant localization of the major Alternaria allergen Alt a 1 in the cell wall of airborne spores. PMID- 22078469 TI - Predetermined challenge eligibility and cessation criteria for oral food challenges in the HealthNuts population-based study of infants. PMID- 22078470 TI - Lung function after viral early childhood wheezing. PMID- 22078473 TI - Comparing activation and recoil forces generated by epinephrine autoinjectors and their training devices. PMID- 22078471 TI - Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease. AB - BACKGROUND: Matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a successful treatment for chronic granulomatous disease (CGD), but the safety and efficacy of HSCT from unrelated donors is less certain. OBJECTIVE: We evaluated the outcomes and overall survival in patients with CGD after HSCT. METHODS: We report the outcomes for 11 children undergoing HSCT from an MRD (n = 4) or an HLA-matched unrelated donor (MUD) (n = 7); 9 children were boys, and the median age was 3.8 years (range, 1-13 years). We treated both X-linked (n = 9) and autosomal recessive (n = 2) disease. Nine children had serious clinical infections before transplantation. The conditioning regimens contained busulfan, cyclophosphamide, cytarabine, or fludarabine according to the donor used. All patients received alemtuzumab (anti-CD52 antibody). Additional graft-versus-host disease (GvHD) prophylaxis included cyclosporine and methotrexate for MUD recipients and cyclosporine and prednisone for MRD recipients. RESULTS: Neutrophil recovery took a median of 16 days (range, 12-40 days) and 18 days (range, 13-24 days) for MRD and MUD recipients, respectively. Full donor neutrophil engraftment occurred in 9 patients, and 2 had stable mixed chimerism; all patients had sustained correction of neutrophil oxidative burst defect. Four patients had grade I skin acute GVHD responding to topical treatment. No patient had grade II to IV acute GvHD or chronic GvHD. All patients are alive between 1 and 8 years after HSCT. CONCLUSION: For CGD, equivalent outcomes can be obtained with MRD or MUD stem cells, and HSCT should be considered an early treatment option. PMID- 22078474 TI - Aggression. PMID- 22078475 TI - Evolutionary aspects of aggression the importance of sexual selection. AB - Aggressive behaviors in animals, for example, threat, attack, and defense, are commonly related to competition over resources, competition over mating opportunities, or fights for survival. In this chapter, we focus on aggressive competition over mating opportunities, since this competition explains much of the distribution of weaponry and large body size, but also because this type of competition sheds light on the sex skew in the use of violence in mammals, including humans. Darwin (1871) termed this type of natural selection, where differences in reproductive success are caused by competition over mates, sexual selection. Not all species have a pronounced competition over mates, however. Instead, this aspect of sociality is ultimately determined by ecological factors. In species where competition over mates is rampant, this has evolutionary effects on weaponry and body size such that males commonly bear more vicious weapons and are larger than females. A review of sexual selection in mammals reveals how common aggressive competition over mating opportunities is in this group. Nearly half of all mammal species exhibit male-biased sexual size dimorphism, a pattern that is clearly linked to sexual selection. Sexual selection is also common in primates, where it has left clear historical imprints in body mass differences, in weaponry differences (canines), and also in brain structure differences. However, when comparing humans to our closest living primate relatives, it is clear that the degree of male sexual competition has decreased in the hominid lineage. Nevertheless, our species displays dimorphism, polygyny, and sex specific use of violence typical of a sexually selected mammal. Understanding the biological background of aggressive behaviors is fundamental to understanding human aggression. PMID- 22078476 TI - Signaling aggression. AB - From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. PMID- 22078477 TI - Self-structuring properties of dominance hierarchies a new perspective. AB - Using aggressive behavior, animals of many species establish dominance hierarchies in both nature and the laboratory. Rank in these hierarchies influences many aspects of animals' lives including their health, physiology, weight gain, genetic expression, and ability to reproduce and raise viable offspring. In this chapter, we define dominance relationships and dominance hierarchies, discuss several model species used in dominance studies, and consider factors that predict the outcomes of dominance encounters in dyads and small groups of animals. Researchers have shown that individual differences in attributes, as well as in states (recent behavioral experiences), influence the outcomes of dominance encounters in dyads. Attributes include physical, physiological, and genetic characteristics while states include recent experiences such as winning or losing earlier contests. However, surprisingly, we marshal experimental and theoretical evidence to demonstrate that these differences have significantly less or no ability to predict the outcomes of dominance encounters for animals in groups as small as three or four individuals. Given these results, we pose an alternative research question: How do animals of so many species form hierarchies with characteristic linear structures despite the relatively low predictability based upon individual differences? In answer to this question, we review the evidence for an alternative approach suggesting that dominance hierarchies are self-structuring. That is, we suggest that linear forms of organization in hierarchies emerge from several kinds of behavioral processes, or sequences of interaction, that are common across many different species of animals from ants to chickens and fish and even some primates. This new approach inspires a variety of further questions for research. PMID- 22078478 TI - Neurogenomic mechanisms of aggression in songbirds. AB - Our understanding of the biological basis of aggression in all vertebrates, including humans, has been built largely upon discoveries first made in birds. A voluminous literature now indicates that hormonal mechanisms are shared between humans and a number of avian species. Research on genetics mechanisms in birds has lagged behind the more typical laboratory species because the necessary tools have been lacking until recently. Over the past 30 years, three major technical advances have propelled forward our understanding of the hormonal, neural, and genetic bases of aggression in birds: (1) the development of assays to measure plasma levels of hormones in free-living individuals, or "field endocrinology"; (2) the immunohistochemical labeling of immediate early gene products to map neural responses to social stimuli; and (3) the sequencing of the zebra finch genome, which makes available a tremendous set of genomic tools for studying gene sequences, expression, and chromosomal structure in species for which we already have large datasets on aggressive behavior. This combination of hormonal, neuroendocrine, and genetic tools has established songbirds as powerful models for understanding the neural basis and evolution of aggression in vertebrates. In this chapter, we discuss the contributions of field endocrinology toward a theoretical framework linking aggression with sex steroids, explore evidence that the neural substrates of aggression are conserved across vertebrate species, and describe a promising new songbird model for studying the molecular genetic mechanisms underlying aggression. PMID- 22078480 TI - The neurochemistry of human aggression. AB - Various data from scientific research studies conducted over the past three decades suggest that central neurotransmitters play a key role in the modulation of aggression in all mammalian species, including humans. Specific neurotransmitter systems involved in mammalian aggression include serotonin, dopamine, norepinephrine, GABA, and neuropeptides such as vasopressin and oxytocin. Neurotransmitters not only help to execute basic behavioral components but also serve to modulate these preexisting behavioral states by amplifying or reducing their effects. This chapter reviews the currently available data to present a contemporary view of how central neurotransmitters influence the vulnerability for aggressive behavior and/or initiation of aggressive behavior in social situations. Data reviewed in this chapter include emoiric information from neurochemical, pharmaco-challenge, molecular genetic and neuroimaging studies. PMID- 22078479 TI - Genetics of aggression in voles. AB - Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form pair bonds-a behavior composed of several social interactions including attachment with a familiar mate and aggression toward conspecific strangers. Therefore, this species has provided an excellent opportunity for the study of pair bonding behavior and its underlying neural mechanisms. In this chapter, we discuss the utility of this unique animal model in the study of aggression and review recent findings illustrating the neurochemical mechanisms underlying pair bonding-induced aggression. Implications of this research for our understanding of the neurobiology of human violence are also discussed. PMID- 22078482 TI - Perinatal risk factors in the development of aggression and violence. AB - Over the past several decades, the relative contribution of both environmental and genetic influences in the development of aggression and violence has been explored extensively. Only fairly recently, however, has it become increasingly evident that early perinatal life events may substantially increase the vulnerability toward the development of violent and aggressive behaviors in offspring across the lifespan. Early life risk factors, such as pregnancy and birth complications and intrauterine exposure to environmental toxins, appear to have a profound and enduring impact on the neuroregulatory systems mediating violence and aggression, yet the emergence of later adverse behavioral outcomes appears to be both complex and multidimensional. The present chapter reviews available experimental and clinical findings to provide a framework on perinatal risk factors that are associated with altered developmental trajectories leading to violence and aggression, and also highlights the genetic contributions in the expression of these behaviors. PMID- 22078481 TI - Human aggression across the lifespan: genetic propensities and environmental moderators. AB - This chapter reviews the recent evidence of genetic and environmental influences on human aggression. Findings from a large selection of the twin and adoption studies that have investigated the genetic and environmental architecture of aggressive behavior are summarized. These studies together show that about half (50%) of the variance in aggressive behavior is explained by genetic influences in both males and females, with the remaining 50% of the variance being explained by environmental factors not shared by family members. Form of aggression (reactive, proactive, direct/physical, indirect/relational), method of assessment (laboratory observation, self-report, ratings by parents and teachers), and age of the subjects-all seem to be significant moderators of the magnitude of genetic and environmental influences on aggressive behavior. Neither study design (twin vs. sibling adoption design) nor sex (male vs. female) seems to impact the magnitude of the genetic and environmental influences on aggression. There is also some evidence of gene-environment interaction (G * E) from both twin/adoption studies and molecular genetic studies. Various measures of family adversity and social disadvantage have been found to moderate genetic influences on aggressive behavior. Findings from these G * E studies suggest that not all individuals will be affected to the same degree by experiences and exposures, and that genetic predispositions may have different effects depending on the environment. PMID- 22078483 TI - Neurocriminology. AB - In the past several decades there has been an explosion of research into the biological correlates to antisocial behavior. This chapter reviews the state of current research on the topic, including a review of the genetics, neuroimaging, neuropsychological, and electrophysiological studies in delinquent and antisocial populations. Special attention is paid to the biopsychosocial model and gene environment interactions in producing antisocial behavior. PMID- 22078484 TI - Prognostic significance of weight changes during treatment of feline lymphoma. AB - The study purpose was to determine the prognostic significance of weight changes during feline lymphoma treatment. A secondary purpose was to compare weight changes according to baseline body weight, cell type and location. Records of 209 cats treated for lymphoma with chemotherapy from 1995 to 2007 were evaluated. Signalment, cell type, lymphoma location, baseline body weight, weight during treatment, and outcome information were collected. Lymphoma specific survival (LSS) was compared according to baseline weight and weight changes during treatment. Weight change over time was compared according to cell type (small versus large), location (gastrointestinal versus non-gastrointestinal) and baseline weight. Cats with large cell lymphoma that lost >= 5% body weight at 1 month had significantly shorter LSS than those that gained or had stable weight (P = 0.004). Percentage weight change over time differed significantly according to baseline weight group. These findings demonstrate the prognostic importance of weight loss in feline large cell lymphoma. PMID- 22078486 TI - VCP mutations in familial and sporadic amyotrophic lateral sclerosis. AB - Mutations in the valosin-containing protein (VCP) gene were recently reported to be the cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases. VCP mutations are known to cause inclusion body myopathy (IBM) with Paget's disease (PDB) and frontotemporal dementia (FTD). The presence of VCP mutations in patients with sporadic ALS, sporadic ALS-FTD, and progressive muscular atrophy (PMA), a known clinical mimic of inclusion body myopathy, is not known. To determine the identity and frequency of VCP mutations we screened a cohort of 93 familial ALS, 754 sporadic ALS, 58 sporadic ALS-FTD, and 264 progressive muscular atrophy patients for mutations in the VCP gene. Two nonsynonymous mutations were detected; 1 known mutation (p.R159H) in a patient with familial ALS with several family members suffering from FTD, and 1 mutation (p.I114V) in a patient with sporadic ALS. Conservation analysis and protein prediction software indicate the p.I114V mutation to be a rare benign polymorphism. VCP mutations are a rare cause of familial ALS. The role of VCP mutations in sporadic ALS, if present, appears limited. PMID- 22078485 TI - Coronary risk correlates with cerebral amyloid deposition. AB - This study investigated the hypothesis that vascular risk factors are amyloidogenic. Participants were 43 persons, most with normal cognition or mild cognitive impairment. Vascular risk was quantified using the Framingham Coronary Risk Profile (FCRP) score. Cerebral amyloid was measured by [(11)C]Pittsburgh compound B (PIB) positron emission tomography (PET) and quantified with a Global PIB index, which is the average of distribution volume ratios in selected cortical regions of interest. In a bivariate model FCRP accounted for 16% of the variance in PIB index (p < 0.008) and the positive association remained significant controlling for age and sex. The effect of FCRP was independent of apolipoprotein E (APOE) genotype, which was also associated as expected with PIB. Carotid intima-media thickness was not associated with PIB index. Effects of individual FCRP component risk factors, cholesterol, and glycemic status on PIB index were all nonsignificant, suggesting an aggregate effect of risk factors. Although this is a correlational observation it may represent a causal relationship as there are multiple, plausible, amyloidogenic mechanisms of vascular risk factors. PMID- 22078487 TI - Targeting poly(ADP-ribose) polymerase-1 as a promising approach for immunomodulation in multiple sclerosis? AB - Despite significant advancement in developing therapies for multiple sclerosis (MS), drugs that cure this devastating disorder are an unmet need. Among the remedies showing efficacy in preclinical MS models, inhibitors of poly(ADP ribose) polymerase (PARP)-1 have gained great momentum. Emerging evidence demonstrates that PARP-1 inhibitors epigenetically regulate gene expression and finely tune transcriptional activation in immune and neural cells. In this review, we present an appraisal of the effects of PARP-1 and its inhibitors on immune activation, with particular emphasis on the processes taking place during the autoimmune attack directed against the central nervous system. One explanation is that drugs inhibiting PARP-1 activity protect from neuroinflammation in MS models via immunomodulation and direct neuroprotection. PARP-1 inhibitors have already reached the clinical arena as cancer treatments, and observations made in treating these patients could help advance treatments for MS. PMID- 22078488 TI - Prognostic factors for short-term improvement in acute and persistent musculoskeletal pain consulters in primary care. AB - BACKGROUND: Given the costs associated with the management of musculoskeletal pain in primary care, predicting the course of these conditions remains a research priority. Much of the research into prognostic indicators however considers musculoskeletal conditions in terms of single pain sites whereas in reality, many patients present with pain in more than one site. The aim of this study was to identify prognostic factors for early improvement in primary care consulters with acute and persistent musculoskeletal conditions across a range of pain sites. METHODS: Consecutive patients with a new episode of musculoskeletal pain completed self-report questionnaires at baseline, and then again at the 4/5th treatment visit, and if they were still consulting, at the 10th visit. The outcome was defined as patient self-report improvement sufficient to make a meaningful difference. Independent predictors of outcome were identified using multivariate regression analyses. RESULTS: Acute (<7 weeks) patients, on average, had more severe conditions in terms of pain, disability, anxiety and work fear avoidance behaviour than patients with persistent (>=7 weeks) pain, but were more likely to be better by the 4/5th visit. Several variables at baseline were associated with improvement at the 4/5th visit, but the predictive models were weak and unable to discriminate between patients who were improved and those who were not. In contrast, it was possible to elicit a predictive model for improvement later on at the 10th visit, but only in patients with persistent pain. Being employed, reporting a decline in work fear-avoidance behaviour at the 4/5th visit, and being better by the 4/5th visit, were all independently associated with improvement. This model accounted for 34.3% (p < 0.001) of the variation in observed improvement, and had good discriminative ability (the area under receiver operating characteristic (ROC) curve was 0.80 (95%CI 0.73 to 0.86)) and approximate balance in correctly identifying improved and non-improved cases (79.0% and 68% respectively). CONCLUSIONS: We were unable to identify baseline characteristics that predicted early outcome in musculoskeletal pain patients. However, early self-reported improvement and decline in work fear avoidance behaviour as predictors of later improvement highlighted the importance of speedy recovery in persistent musculoskeletal pain consulters. Our findings reinforce the elusive nature of baseline predictors, and the need for more emphasis on early changes as prognostic predictors in musculoskeletal conditions. PMID- 22078489 TI - A kinetic study of SDF-1, VEGF and MCP-1 blood and tissue levels after aortic transplantation in mice. AB - Vascular rejection is characterized by intimal proliferation and perivascular inflammation. We hypothesize that recipient stem cell therapy could prevent or ameliorate the development of the obliterative lesion. We studied the kinetic expression of three cytokines (SDF-1, MCP-1, VEGF) implicated in mobilization, homing and differentiation of progenitor cells during vascular aggression. An aortic allograft mouse model was used (BALBc donor-C57BL6/j recipient). Ten mice were sacrificed at Day 0, D1, D3, D6, D9, D12, and D20. Cytokine rates were measured in blood and in graft tissue by an ELISA technique. Results showed that in the allograft, SDF-1 and VEGF tissue levels were significantly increased at D12 as compared to the isograft (SDF-1: 22.16 ng/mg vs. 5.69 ng/mg, t=3.38; VEGF: 28.3 pg/mg vs. 9.3 pg/mg, t=3.06). In allografted and isografted groups, MCP-1 tissue levels were higher at D0 as compared to the other time points, without any difference between the two groups. These results prompt us to consider cell therapy at D0 and D12 in this mouse model of aortic graft. PMID- 22078491 TI - Dissolution kinetics of Pd and Pt from automobile catalysts by naturally occurring complexing agents. AB - Powder samples prepared from gasoline (Pt, Pd, Rh, new GN/old GO) and diesel (Pt, new DN/old DO) catalysts and recycled catalyst NIST 2556 were tested using kinetic leaching experiments following 1, 12, 24, 48, 168, 360, 720 and 1440-h interactions with solutions of 20mM citric acid (CA), 20 mM Na(2)P(4)O(7) (NaPyr), 1 g L(-1) NaCl (NaCl), a fulvic acid solution (FA-DOC 50 mg L(-1)) and 20 mM CA at pH 3, 4, 5, 6, 7, 8 and 9. The mobilisation of platinum group elements (PGEs) was fastest in solutions of CA and NaPyr. In the other interactions (NaCl, FA), the release of PGEs was probably followed by immobilisation processes, and the interactions were not found to correspond to the simple release of PGEs into solution. Because of their low concentrations, the individual complexing agents did not have any effect on the speciation of Pd and Pt in the extracts; both metals are present in solution as the complexes Me(OH)(2), Me(OH)(+). Immobilisation can take place through the adsorption of the positively charged hydroxyl complexes or flocculation of fulvic acid, complexing the PGEs on the surface of the extracted catalysts. The calculated normalised bulk released NRi values are similar to the reaction rate highest in the solutions of CA and NaPyr. PMID- 22078492 TI - The use of carbon black to catalyze the reduction of nitrobenzenes by sulfides. AB - Using carbon black (CB) as catalyst, the reduction of nitrobenzenes (NBs) to anilines by sulfides at room temperature was studied. In the reactions, CB serves as an intermedium to accelerate the reduction of NBs by sulfides. In the presence of 0.3g/L CB and 3.0 mM sulfides at pH 7.0 and 25 degrees C, our results showed that CB-catalyzed reduction of NBs were pseudo-first order. The reduction rate constant of nitrobenzene was 0.0367 h(-1) in the presence of CB-1, which was 10 times more than the reduction rate constant in the absence of CB-1. Other experiments of different CB samples produced by different methods and different raw materials indicated that some active oxygenated functional groups on CB surface should be the reactive sites and play the dominant role in catalyzing the reduction of NBs. The catalytic reactions of different NBs by sulfides indicated that the reduction rate constants of chloronitrobenzenes to chloroanilines were greater than those of methylnitrobenzenes to methylanilines. And due to the effect of different substituent positions, the nitro group with meta substituent was reduced most easily while the nitro group with ortho substituent was reduced most difficulty. PMID- 22078490 TI - Effectiveness of a structured motivational intervention including smoking cessation advice and spirometry information in the primary care setting: the ESPITAP study. AB - BACKGROUND: There is current controversy about the efficacy of smoking cessation interventions that are based on information obtained by spirometry. The objective of this study is to evaluate the effectiveness in the primary care setting of structured motivational intervention to achieve smoking cessation, compared with usual clinical practice. METHODS: DESIGN: Multicentre randomized clinical trial with an intervention and a control group. SETTING: 12 primary care centres in the province of Tarragona (Spain). SUBJECTS OF STUDY: 600 current smokers aged between 35 and 70 years with a cumulative habit of more than 10 packs of cigarettes per year, attended in primary care for any reason and who did not meet any of the exclusion criteria for the study, randomly assigned to structured intervention or standard clinical attention. INTERVENTION: Usual advice to quit smoking by a general practitioner as well as a 20-minute personalized visit to provide detailed information about spirometry results, during which FEV1, FVC, FEF 25-75% and PEF measurements were discussed and interpreted in terms of theoretical values. Additional information included the lung age index (defined as the average age of a non-smoker with the same FEV1 as the study participant), comparing this with the chronological age to illustrate the pulmonary deterioration that results from smoking. MEASUREMENTS: Spirometry during the initial visit. Structured interview questionnaire administered at the primary care centre at the initial visit and at 12-month follow-up. Telephone follow-up interview at 6 months. At 12-month follow-up, expired CO was measured in patients who claimed to have quit smoking. MAIN VARIABLES: Smoking cessation at 12 months. ANALYSIS: Data will be analyzed on the basis of "intention to treat" and the unit of analysis will be the individual smoker. EXPECTED RESULTS: Among active smokers treated in primary care we anticipate significantly higher smoking cessation in the intervention group than in the control group. DISCUSSION: Application of a motivational intervention based on structured information about spirometry results, improved abstinence rates among smokers seen in actual clinical practice conditions in primary care. TRIAL REGISTRATION: ClinicalTrial.gov, number NCT01194596. PMID- 22078493 TI - Left ventricular outflow tract: intraoperative measurement and changes caused by mitral valve surgery. AB - BACKGROUND: The impact of mitral valve surgery on left ventricular outflow tract (LVOT) dimensions is unclear. Real-time three-dimensional transesophageal echocardiography permits excellent visualization of the LVOT and might improve standard two-dimensional measurements. In this study, LVOT area and shape were assessed before and after mitral valve surgery. METHODS: Thirty-five patients undergoing mitral valve repair or replacement were retrospectively included in the study and compared with 15 patients undergoing coronary artery bypass grafting. LVOT area was measured by planimetry. Maximum possible methodologic errors by assuming a circular LVOT and an eccentricity index were calculated. LVOT diameter in a midesophageal long-axis view served to calculate the error for the circular LVOT determined in common intraoperative practice. RESULTS: Common intraoperative two-dimensional measurements underestimated actual LVOT area by 21%. Mitral valve surgery led to a significant reduction of LVOT area by 7%. Although LVOT height remained unchanged, width decreased from 2.72 to 2.53 cm ( 7%), resulting in a more circular shape of the LVOT. This effect was more pronounced the smaller the size of the implanted annuloplasty ring or prosthesis. Coronary artery bypass grafting did not affect the LVOT. Left ventricular ejection fraction was significantly correlated with LVOT eccentricity. Impaired ventricular function and higher end-systolic volumes were associated with a rounder shape. CONCLUSIONS: The eccentric LVOT shape leads to a distinct underestimation of its area with two-dimensional measurements. LVOT eccentricity is less distinct in patients with low ejection fractions and higher end-systolic volumes. LVOT width is decreased through annuloplasty rings and prostheses, and the smaller the implanted device, the more profound the reduction. PMID- 22078494 TI - Probucol alleviates atherosclerosis and improves high density lipoprotein function. AB - BACKGROUND: Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDL-C). However, it is not definite that whether probucol hinders the progression of atherosclerosis by improving HDL function. METHODS: Eighteen New Zealand White rabbits were randomly divided into the control, atherosclerosis and probucol groups. Control group were fed a regular diet; the atherosclerosis group received a high fat diet, and the probucol group received the high fat diet plus probucol. Hepatocytes and peritoneal macrophages were isolated for [(3)H] labeled cholesterol efflux rates and expression of ABCA1 and SR-B1 at gene and protein levels; venous blood was collected for serum paraoxonase 1, myeloperoxidase activity and lipid analysis. Aorta were prepared for morphologic and immunohistochemical analysis after 12 weeks. RESULTS: Compared to the atherosclerosis group, the paraoxonase 1 activity, cholesterol efflux rates, expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages, and the level of ABCA1 and SR-BI in aortic lesions were remarkably improved in the probucol group, But the serum HDL cholesterol concentration, myeloperoxidase activity, the IMT and the percentage plaque area of aorta were significantly decreased. CONCLUSION: Probucol alleviated atherosclerosis by improving HDL function. The mechanisms include accelerating the process of reverse cholesterol transport, improving the anti-inflammatory and anti-oxidant functions. PMID- 22078495 TI - Association of an ACSL1 gene variant with polyunsaturated fatty acids in bovine skeletal muscle. AB - BACKGROUND: The intramuscular fat deposition and the fatty acid profiles of beef affect meat quality. High proportions of unsaturated fatty acids are related to beef flavor and are beneficial for the nutritional value of meat. Moreover, a variety of clinical and epidemiologic studies showed that particularly long-chain omega-3 fatty acids from animal sources have a positive impact on human health and disease. RESULTS: To screen for genetic factors affecting fatty acid profiles in beef, we initially performed a microsatellite-based genome scan in a F(2) Charolais * German Holstein resource population and identified a quantitative trait locus (QTL) for fatty acid composition in a region on bovine chromosome 27 where previously QTL affecting marbling score had been detected in beef cattle populations. The long-chain acyl-CoA synthetase 1 (ACSL1) gene was identified as the most plausible functional and positional candidate gene in the QTL interval due to its direct impact on fatty acid metabolism and its position in the QTL interval. ACSL1 is necessary for synthesis of long-chain acyl-CoA esters, fatty acid degradation and phospholipid remodeling. We validated the genomic annotation of the bovine ACSL1 gene by in silico comparative sequence analysis and experimental verification. Re-sequencing of the complete coding, exon-flanking intronic sequences, 3' untranslated region (3'UTR) and partial promoter region of the ACSL1 gene revealed three synonymous mutations in exons 6, 7, and 20, six noncoding intronic gene variants, six polymorphisms in the promoter region, and four variants in the 3' UTR region. The association analysis identified the gene variant in intron 5 of the ACSL1 gene (c.481-233A>G) to be significantly associated with the relative content of distinct fractions and ratios of fatty acids (e.g., n-3 fatty acids, polyunsaturated, n-3 long-chain polyunsaturated fatty acids, trans vaccenic acid) in skeletal muscle. A tentative association of the ACSL1 gene variant with intramuscular fat content indicated that an indirect effect on fatty acid composition via modulation of total fat content of skeletal muscle cannot be excluded. CONCLUSIONS: The initial QTL analysis suggested the ACSL1 gene as a positional and functional candidate gene for fatty acid composition in bovine skeletal muscle. The findings of subsequent association analyses indicate that ACSL1 or a separate gene in close proximity might play a functional role in mediating the lipid composition of beef. PMID- 22078497 TI - Occurrence, types and severity of associated injuries of paediatric patients with fractures of the frontal skull base. AB - OBJECTIVES: To clarify the occurrence, sites, and types of associated injuries in paediatric patients with fractures of the anterior skull base. STUDY DESIGN: Retrospective analysis of files of 49 patients aged up to 18 years. RESULTS: Associated injuries were observed in 91.8% of the patients. Observed most frequently were fractures of the skull vault (85.7%), brain injury (59.2%), facial fracture (42.9%), lung contusion (18.4%) and fractures of the upper extremities (14.3%). Multiple injuries were observed in 55.1% and polytrauma in 42.9%. The mortality rate was 10.2%. CONCLUSIONS: Paediatric patients with fractures of the anterior skull base frequently present with associated injuries, with many having, multiple associated injuries including polytrauma. These patients should be treated in multidisciplinary trauma units. PMID- 22078496 TI - Molecular basis for interaction of let-7 microRNAs with Lin28. AB - MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression. Among these, members of the let-7 miRNA family control many cell-fate determination genes to influence pluripotency, differentiation, and transformation. Lin28 is a specific, posttranscriptional inhibitor of let-7 biogenesis. We report crystal structures of mouse Lin28 in complex with sequences from let-7d, let-7-f1, and let-7 g precursors. The two folded domains of Lin28 recognize two distinct regions of the RNA and are sufficient for inhibition of let-7 in vivo. We also show by NMR spectroscopy that the linker connecting the two folded domains is flexible, accommodating Lin28 binding to diverse let-7 family members. Protein-RNA complex formation imposes specific conformations on both components that could affect downstream recognition by other processing factors. Our data provide a molecular explanation for Lin28 specificity and a model for how it regulates let-7. PMID- 22078498 TI - Three-dimensional analyses of facial soft tissue configuration of Japanese females with jaw deformity--a trial of polygonal view of facial soft tissue deformity in orthognathic patients. AB - In this study, we evaluated the three-dimensional (3D) soft tissue configuration of Japanese females with/without jaw deformity in order to establish the polygonal view of facial soft tissue deformity three-dimensionally. A polygonal chart was applied to assess the outcomes of orthognathic surgery for patients with mandibular hyperplasia with/without deviation. The study included 20 Japanese females with mandibular hyperplasia with/without deviation. All patients received mandibular setback surgery, and 3D measurements were carried out pre operation, and at 1, 3 and 6 months postoperatively using a non-contact laser scanning system. Eighteen soft tissue landmarks were set on each 3D image and used to calculate a set of selected parameters. As controls, 20 Japanese females with class I occlusion were included. A polygonal chart was constructed based on the mean and S.D. of the control group. Patients with mandibular protrusion characteristically demonstrated significant variances in the items around the lower face. In asymmetric patients, deviation in the mental area disappeared postoperatively, but a small deviation remained when compared to the controls. The method used in this study seems to be a useful index for diagnosis and as a treatment plan for patients with mandibular hyperplasia with/without deviation. PMID- 22078499 TI - The clinical application of the dental mini C-arm for the removal of broken instruments in soft and hard tissue in the oral and maxillofacial area. AB - Many kinds of broken instruments, such as needles, probes, scalpels and catheters, are reported to be left in patients after surgery. These parts should be removed as soon as possible to prevent further complications. However, it is not easy to identify the exact location of the instrument intraoperatively, and a risk of damage exists for neighbouring nerves or vessels during the removal. The C-arm used in orthopaedic surgery, is seen as a useful and safe way to detect metal materials intraoperatively. However, its application for removal of broken instruments in the oral and maxillofacial area is not practical because of its large size. In our experiences with the removal of eight broken instruments in the oral and maxillofacial area, the newly developed dental mini C-arm was useful in finding broken instruments in soft tissue (five cases) and in paranasal sinus (one case), because it gives real time in situ information. This is important, because the position of the broken instrument can be changed due to traction of the soft tissue or swelling. The dental mini C-arm was less helpful in finding broken instruments in soft tissues compared to hard tissues (two cases) as the position of instruments did not change. PMID- 22078500 TI - A statistical study of the factors influencing the extent of respiratory motion blur in PET imaging. AB - Respiratory motion results in significant motion blur in thoracic and abdomen PET imaging. The extent of respiratory motion blur is mainly correlated with breathing amplitude, tumor size and location. In this paper we introduce a statistical study to quantitatively show the factors influencing the extent of respiratory motion blur in thoracic PET images. The study is centered on two regression models, one is linked with motion blur induced loss of mean intensity(LMI), tumor motion magnitude and tumor size, and another is to investigate the influence of tumor location, patient gender and patient height on tumor motion magnitude. We use the blur identification and image restoration technique to estimate the tumor motion and compute the LMI. The regression model was validated by simulation and phantom data before extended to 39 cases of clinical lung tumor PET images corrupted with blurring artifact. Results show that the motion magnitude of lung tumor during breathing is 10.9+/-3.7mm in transaxial plane, and it is significantly greater in lower lung lobes than in upper lobes. The LMI is 7.1+/-2.4% in the region of interest (ROI) above 40% of the image's maximum intensity. The least-square estimate of regression equations demonstrates that LMI is proportional to tumor motion magnitude and is inversely proportional to tumor size; the two factors play the same role in determining the extent of respiratory motion blur in thoraco-abdominal PET imaging. The location of tumor was shown as the major factor determining its motion magnitude, while the influencing of patient gender and height on tumor motion was not shown significant. PMID- 22078501 TI - Special issue on techniques for measuring brain connectivity. PMID- 22078502 TI - Motor neurons and the sense of place. AB - Seventy years ago George Romanes began to document the anatomical organization of the spinal motor system, uncovering a multilayered topographic plan that links the clustering and settling position of motor neurons to the spatial arrangement and biomechanical features of limb muscles. To this day, these findings have provided a structural foundation for analysis of the neural control of movement and serve as a guide for studies to explore mechanisms that direct the wiring of spinal motor circuits. In this brief essay we outline the core of Romanes's findings and place them in the context of recent studies that begin to provide insight into molecular programs that assign motor pool position and to resolve how motor neuron position shapes circuit assembly. Romanes's findings reveal how and why neuronal positioning contributes to sensory-motor connectivity and may have relevance to circuit organization in other regions of the central nervous system. PMID- 22078503 TI - Computational mechanisms of sensorimotor control. AB - In order to generate skilled and efficient actions, the motor system must find solutions to several problems inherent in sensorimotor control, including nonlinearity, nonstationarity, delays, redundancy, uncertainty, and noise. We review these problems and five computational mechanisms that the brain may use to limit their deleterious effects: optimal feedback control, impedance control, predictive control, Bayesian decision theory, and sensorimotor learning. Together, these computational mechanisms allow skilled and fluent sensorimotor behavior. PMID- 22078504 TI - Neuroplasticity subserving motor skill learning. AB - Recent years have seen significant progress in our understanding of the neural substrates of motor skill learning. Advances in neuroimaging provide new insight into functional reorganization associated with the acquisition, consolidation, and retention of motor skills. Plastic changes involving structural reorganization in gray and white matter architecture that occur over shorter time periods than previously thought have been documented as well. Data from experimental animals provided crucial information on plausible cellular and molecular substrates contributing to brain reorganization underlying skill acquisition in humans. Here, we review findings demonstrating functional and structural plasticity across different spatial and temporal scales that mediate motor skill learning while identifying converging areas of interest and possible avenues for future research. PMID- 22078505 TI - Neuronal basis for object location in the vibrissa scanning sensorimotor system. AB - An essential issue in perception is how the location of an object is estimated from tactile signals in the context of self-generated changes in sensor configuration. Here, we review the pathways and dynamics of neuronal signals that encode touch in the rodent vibrissa sensorimotor system. Rodents rhythmically scan an array of long, facial hairs across a region of interest. Behavioral evidence shows that these animals maintain knowledge of the azimuthal position of their vibrissae. Electrophysiological measurements have identified a reafferent signal of the azimuth that is coded in normalized coordinates, broadcast throughout primary sensory cortex and provides strong modulation of signals of vibrissa contact. Efferent signals in motor cortex report the range of the scan. Collectively, these signals allow the rodent to form a percept of object location. PMID- 22078506 TI - Are we ready for a natural history of motor learning? AB - Here we argue that general principles with regard to the contributions of the cerebellum, basal ganglia, and primary motor cortex to motor learning can begin to be inferred from explicit comparison across model systems and consideration of phylogeny. Both the cerebellum and the basal ganglia have highly conserved circuit architecture in vertebrates. The cerebellum has consistently been shown to be necessary for adaptation of eye and limb movements. The precise contribution of the basal ganglia to motor learning remains unclear but one consistent finding is that they are necessary for early acquisition of novel sequential actions. The primary motor cortex allows independent control of joints and construction of new movement synergies. We suggest that this capacity of the motor cortex implies that it is a necessary locus for motor skill learning, which we argue is the ability to execute selected actions with increasing speed and precision. PMID- 22078508 TI - What is optimal about motor control? AB - This article poses a controversial question: is optimal control theory useful for understanding motor behavior or is it a misdirection? This question is becoming acute as people start to conflate internal models in motor control and perception (Poeppel et al., 2008; Hickok et al., 2011). However, the forward models in motor control are not the generative models used in perceptual inference. This Perspective tries to highlight the differences between internal models in motor control and perception and asks whether optimal control is the right way to think about things. The issues considered here may have broader implications for optimal decision theory and Bayesian approaches to learning and behavior in general. PMID- 22078507 TI - Sensing with the motor cortex. AB - The primary motor cortex is a critical node in the network of brain regions responsible for voluntary motor behavior. It has been less appreciated, however, that the motor cortex exhibits sensory responses in a variety of modalities including vision and somatosensation. We review current work that emphasizes the heterogeneity in sensorimotor responses in the motor cortex and focus on its implications for cortical control of movement as well as for brain-machine interface development. PMID- 22078509 TI - The future of automated seizure detection and prediction: foreword. PMID- 22078510 TI - Computational model prospective on the observation of proictal states in epileptic neuronal systems. AB - Epilepsy is a pathological condition of the human central nervous system in which normal brain functions are impaired by unexpected transitions to states called seizures. We developed a lumped neuronal model that has the property of switching between two states as a result of intrinsic or extrinsic perturbations, such as noisy fluctuations. In one version of the model, seizure risk is controlled by a single connectivity parameter representing excitatory couplings between two model lumps. We show that this risk can be reconstructed from calculation of the cross covariance between the activities of the two neural populations during the nonictal phase. In a second simulation sequence, we use a system of 10 interconnected lumps with randomly generated connectivity matrices. We show again that the tendency to develop seizures can be inferred from the cross-covariances calculated during the nonictal states. Our conclusion is that the risk of epileptic transitions in biological systems can be objectively quantified. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078511 TI - Electrical probing of cortical excitability in patients with epilepsy. AB - Standard methods for seizure prediction involve passive monitoring of intracranial electroencephalography (iEEG) in order to track the 'state' of the brain. This paper introduces a new method for measuring cortical excitability using an electrical probing stimulus. Electrical probing enables feature extraction in a more robust and controlled manner compared to passively tracking features of iEEG signals. The probing stimuli consist of 100 bi-phasic pulses, delivered every 10 min. Features representing neural excitability are estimated from the iEEG responses to the stimuli. These features include the amplitude of the electrically evoked potential, the mean phase variance (univariate), and the phase-locking value (bivariate). In one patient, it is shown how the features vary over time in relation to the sleep-wake cycle and an epileptic seizure. For a second patient, it is demonstrated how the features vary with the rate of interictal discharges. In addition, the spatial pattern of increases and decreases in phase synchrony is explored when comparing periods of low and high interictal discharge rates, or sleep and awake states. The results demonstrate a proof-of-principle for the method to be applied in a seizure anticipation framework. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078512 TI - Anticipating the unobserved: prediction of subclinical seizures. AB - Subclinical seizures (SCS) have rarely been considered in the diagnosis and therapy of epilepsy and have not been systematically analyzed in studies on seizure prediction. Here, we investigate whether predictions of subclinical seizures are feasible and how their occurrence may affect the performance of prediction algorithms. Using the European database of long-term recordings of surface and invasive electroencephalography data, we analyzed the data from 21 patients with SCS, including in total 413 clinically manifest seizures (CS) and 3341 SCS. Based on the mean phase coherence we investigated the predictive performance of CS and SCS. The two types of seizures had similar prediction sensitivities. Significant performance was found considerably more often for SCS than for CS, especially for patients with invasive recordings. When analyzing false alarms triggered by predicting CS, a significant number of these false predictions were followed by SCS for 9 of 21 patients. Although currently observed prediction performance may not be deemed sufficient for clinical applications for the majority of the patients, it can be concluded that the prediction of SCS is feasible on a similar level as for CS and allows a prediction of more of the seizures impairing patients, possibly also reducing the number of false alarms that were in fact correct predictions of CS. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078513 TI - Toward a probabilistic definition of seizures. AB - This writing (1) draws attention to the intricacies inherent to the pursuit of a universal seizure definition even when powerful, well-understood signal analysis methods are used to this end; (2) identifies this aim as a multi-objective optimization problem and discusses the advantages and disadvantages of adopting or rejecting a unitary seizure definition; and (3) introduces a probabilistic measure of seizure activity to manage this thorny issue. The challenges posed by the attempt to define seizures unitarily may be partly related to their fractal properties and understood through a simplistic analogy to the so-called "Richardson effect." A revision of the time-honored conceptualization of seizures may be warranted to further advance epileptology. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078514 TI - A few thoughts on "What is a seizure?". PMID- 22078515 TI - An algorithm for seizure onset detection using intracranial EEG. AB - This article addresses the problem of real-time seizure detection from intracranial EEG (IEEG). One difficulty in creating an approach that can be used for many patients is the heterogeneity of seizure IEEG patterns across different patients and even within a patient. In addition, simultaneously maximizing sensitivity and minimizing latency and false detection rates has been challenging as these are competing objectives. Automated machine learning systems provide a mechanism for dealing with these hurdles. Here we present and evaluate an algorithm for real-time seizure onset detection from IEEG using a machine learning approach that permits a patient-specific solution. We extract temporal and spectral features across all intracranial EEG channels. A pattern recognition component is trained using these feature vectors and tested against unseen continuous data from the same patient. When tested on more than 875 hours of IEEG data from 10 patients, the algorithm detected 97% of 67 test seizures of several types with a median detection delay of 5 seconds and a median false alarm rate of 0.6 false alarms per 24-hour period. The sensitivity was 100% for 8 of 10 patients. These results indicate that a sensitive, specific, and relatively short latency detection system based on machine learning can be employed for seizure detection from EEG using a full set of intracranial electrodes to individual patients. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078516 TI - A machine-learning algorithm for detecting seizure termination in scalp EEG. AB - Efforts to develop algorithms that can robustly detect the cessation of seizure activity within scalp EEGs are now underway. Such algorithms can facilitate novel clinical applications such as the estimation of a seizure's duration; the delivery of therapies designed to mitigate postictal period symptoms; or detection of the presence of status epilepticus. In this article, we present and evaluate a novel, machine learning-based method for detecting the termination of electrographic seizure activity. When tested on 133 seizures from a public database, our method successfully detected the end of 132 seizures within 10.3 +/ 5.5 seconds of the time determined by an electroencephalographer to represent the electrographic end of seizure. Furthermore, by pairing our seizure end detector with a previously published seizure onset detector, we could automatically estimate the duration of 85% of test electrographic seizures within a 15-second error margin compared with electroencephalographer determinations. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078517 TI - Automated EEG detection algorithms and clinical semiology in epilepsy: importance of correlations. AB - With advances in technological innovation, electroencephalography has remained the gold standard for classification and localization of epileptic seizures. Like other diagnostic modalities, technological advances have opened new avenues for assessment of data, and hold great promise to improve interpretive capabilities. However, proper overall interpretation and application of electroencephalographic findings relies on valid correlations of associated clinical semiology. This article addresses interpretation of clinical signs and symptoms in the context of the diagnostic predictive value of electroencephalographic, clinical, and electrographic definitions of seizures, and upcoming challenges of interpreting intracranial high-frequency electroencephalographic data. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078518 TI - Improving early seizure detection. AB - Over the last decade, the search for a method able to reliably predict seizures hours in advance has been largely replaced by the more realistic goal of very early detection of seizure onset, which would allow therapeutic or warning devices to be triggered prior to the onset of disabling clinical symptoms. We explore in this article the steps along the pathway from data acquisition to closed-loop applications that can and should be considered to design the most efficient early seizure detection. Microelectrodes, high-frequency oscillations, high sampling rate, high-density arrays, and modern analysis techniques are all elements of the recording and detection process that in combination with modeling studies can provide new insights into the dynamics of seizure onsets. Each of these steps needs to be considered if detection devices that will favorably impact the quality of life of patients are to be implemented. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078519 TI - Quickest detection of drug-resistant seizures: an optimal control approach. AB - Epilepsy affects 50 million people worldwide, and seizures in 30% of the cases remain drug resistant. This has increased interest in responsive neurostimulation, which is most effective when administered during seizure onset. We propose a novel framework for seizure onset detection that involves (i) constructing statistics from multichannel intracranial EEG (iEEG) to distinguish nonictal versus ictal states; (ii) modeling the dynamics of these statistics in each state and the state transitions; you can remove this word if there is no room. (iii) developing an optimal control-based "quickest detection" (QD) strategy to estimate the transition times from nonictal to ictal states from sequential iEEG measurements. The QD strategy minimizes a cost function of detection delay and false positive probability. The solution is a threshold that non-monotonically decreases over time and avoids responding to rare events that normally trigger false positives. We applied QD to four drug resistant epileptic patients (168 hour continuous recordings, 26-44 electrodes, 33 seizures) and achieved 100% sensitivity with low false positive rates (0.16 false positive/hour). This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078520 TI - Multistage seizure detection techniques optimized for low-power hardware platforms. AB - Closed-loop neurostimulation devices that stimulate the brain to treat epileptic seizures have shown great promise in treating more than a third of the 2 million people with epilepsy in the United States alone whose seizures are currently nonresponsive to pharmaceutical treatment. Seizure detection algorithms facilitate responsive therapeutic intervention that is believed to increase the efficacy of neurostimulation by improving on its spatial and temporal specificity. Translating these signal processing algorithms into battery-powered, implantable devices poses a number of challenges that severely limit the computational power of the chosen algorithm. We propose a cascaded two-stage seizure detection algorithm that is computationally efficient (resulting in a low power hardware implementation) without compromising on detection efficacy. Unlike traditional detection algorithms, the proposed technique does not explicitly require a "training" phase from individual to individual and, instead, relies on using features that result in distinct "patterns" at the electrographic seizure onset. We tested the algorithm on spontaneous clinical seizures recorded using depth electrodes from patients with focal intractable epilepsy and annotated by epileptologists at the University of Freiburg Medical Center, via the Freiburg database. The algorithm performs with a specificity and sensitivity of 99.82 and 87.5%, detecting seizures in less than 9.08% of their duration after onset. The proposed technique is also shown to be computationally efficient, facilitating low-power hardware implementation. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078521 TI - Quantitative EEG analysis for automated detection of nonconvulsive seizures in intensive care units. AB - Because of increased awareness of the high prevalence of nonconvulsive seizures in critically ill patients, use of continuous EEG (cEEG) monitoring is rapidly increasing in ICUs. However, cEEG monitoring is labor intensive, and manual review and interpretation of the EEG are impractical in most ICUs. Effective methods to assist in rapid and accurate detection of nonconvulsive seizures would greatly reduce the cost of cEEG monitoring and enhance the quality of patient care. In this study, we report a preliminary investigation of a novel ICU EEG analysis and seizure detection algorithm. Twenty-four prolonged cEEG recordings were included in this study. Seizure detection sensitivity and specificity were assessed for the new algorithm and for the two commercial seizure detection software systems. The new algorithm performed with a mean sensitivity of 90.4% and a mean false detection rate of 0.066/hour. The two commercial detection products performed with low sensitivities (12.9 and 10.1%) and false detection rates of 1.036/hour and 0.013/hour, respectively. These findings suggest that the novel algorithm has potential to be the basis of clinically useful software that can assist ICU staff in timely identification of nonconvulsive seizures. This study also suggests that currently available seizure detection software does not perform sufficiently in detection of nonconvulsive seizures in critically ill patients. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078522 TI - Automated seizure detection: unrecognized challenges, unexpected insights. AB - One of epileptology's fundamental aims is the formulation of a universal, internally consistent seizure definition. To assess this aim's feasibility three signal analysis methods were applied to a seizure time series and performance comparisons were undertaken among them and with respect to a validated algorithm. One of the methods uses a Fisher's matrix weighted measure of the rate of parameters change of a 2nd order auto-regressive model, another is based on the Wavelet Transform Maximum Modulus for quantification of changes in the logarithm of the standard deviation of ECoG power and yet another employs the ratio of short-to-long term averages computed from cortical signals. The central finding, fluctuating concordance among all methods' output as a function of seizure duration, uncovers unexpected hurdles in the path to a universal definition, while furnishing relevant knowledge in the dynamical (spectral non stationarity/varying ictal signal complexity) and clinical (potential un attainability of consensus) domains. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078523 TI - Resetting of brain dynamics: epileptic versus psychogenic nonepileptic seizures. AB - We investigated the possibility of differential diagnosis of patients with epileptic seizures (ES) and patients with psychogenic nonepileptic seizures (PNES) through an advanced analysis of the dynamics of the patients' scalp EEGs. The underlying principle was the presence of resetting of brain's preictal spatiotemporal entrainment following onset of ES and the absence of resetting following PNES. Long-term (days) scalp EEGs recorded from five patients with ES and six patients with PNES were analyzed. It was found that: (1) Preictal entrainment of brain sites was reset at ES (P<0.05) in four of the five patients with ES, and not reset (P=0.28) in the fifth patient. (2) Resetting did not occur (p>0.1) in any of the six patients with PNES. These preliminary results in patients with ES are in agreement with our previous findings from intracranial EEG recordings on resetting of brain dynamics by ES and are expected to constitute the basis for the development of a reliable and supporting tool in the differential diagnosis between ES and PNES. Finally, we believe that these results shed light on the electrophysiology of PNES by showing that occurrence of PNES does not assist patients in overcoming a pathological entrainment of brain dynamics. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078524 TI - Extracerebral detection of seizures: a new era in epileptology? AB - The medical and psycho-socio-economic burden imposed on patients, caregivers, and health systems by pharmacoresistant epilepsies is enormous. Intracranial devices for automated detection, warning, and delivery of therapy, the presently preferred "line of attack" for an abundance of weighty reasons, would be insufficient to adequately address said burden on a global scale. Reliance on signals that, although extracerebral, are under cortical modulation or control and are altered by seizures, such as cardiac or motor signals, emerges as a viable research direction with potentially fruitful clinical applications. The greater ease of implementation and lower cost of automated real-time detection, warning, and therapy systems based on extracerebral signals, compared with those requiring intracranial placement, make them worthy of investigation. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078525 TI - The role of high-quality EEG databases in the improvement and assessment of seizure prediction methods. AB - Initially, seizure prediction was based on the analysis of brief EEG segments preceding clinically manifest seizures. Whereas such approaches suggested that the sensitivities of various EEG-derived features in predicting seizures were high, the inclusion of longer interictal periods and the combined assessment of sensitivity and specificity and the application of statistical validation methods have put into question the validity of such claims. We here show that the duration of EEG on which analyses are based and the number of seizures assessed negatively correlate with the reported sensitivities of prediction studies. Methodological aspects of seizure prediction are discussed in the framework of currently existing databases and of the newly established European Union database. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078527 TI - Intracellular production of recombinant serpins in yeast. AB - Yeast are a valuable system for recombinant serpin production due to their ability to synthesize large amounts of heterologous gene products as well as their expression of folding chaperones and lack of endogenous serpin genes. In this chapter, we describe a method for intracellular expression of cytoplasmic serpins in the yeast Pichia pastoris. We also give details on how this system can be exploited to produce polymer-forming mutants of secretory serpins. PMID- 22078526 TI - Seizure prediction: methods. AB - Epilepsy, one of the most common neurological diseases, affects over 50 million people worldwide. Epilepsy can have a broad spectrum of debilitating medical and social consequences. Although antiepileptic drugs have helped treat millions of patients, roughly a third of all patients have seizures that are refractory to pharmacological intervention. The evolution of our understanding of this dynamic disease leads to new treatment possibilities. There is great interest in the development of devices that incorporate algorithms capable of detecting early onset of seizures or even predicting them hours before they occur. The lead time provided by these new technologies will allow for new types of interventional treatment. In the near future, seizures may be detected and aborted before physical manifestations begin. In this chapter we discuss the algorithms that make these devices possible and how they have been implemented to date. We also compare and contrast these measures, and review their individual strengths and weaknesses. Finally, we illustrate how these techniques can be combined in a closed-loop seizure prevention system. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. PMID- 22078528 TI - Production of recombinant serpins in Escherichia coli. AB - Serpins represent a diverse family of proteins that are found in a wide range of organisms and cellular locations. In order to study them, most need to be produced recombinantly, as isolation from their source is not always possible. Due to their relatively uncomplicated structure (single domain, few posttranslational modifications), the serpins are usually amenable to expression in Escherichia coli, which offers a fast and cost-effective solution for the generation of large amounts of protein. This chapter outlines the general procedures used in the expression and subsequent purification of serpins in E. coli, with a particular focus on the methods used for antitrypsin, the archetypal member of the family. PMID- 22078529 TI - Isolation and characterization of the nuclear serpin MENT. AB - A balance between proteolytic activity and protease inhibition is required to maintain the appropriate function of biological systems in which proteases play a role. The Myeloid and Erythroid Nuclear Termination protein, MENT, is a nonhistone heterochromatin-associated serpin that is an effective inhibitor of the papain-like cysteine proteases. Our laboratories have extensively investigated the dual functions of this protein, namely, chromatin condensation and protease inhibition. Unlike other serpins to date, MENT contains a unique insertion between the C- and D-helices known as the "M-loop." This loop contains two critical functional motifs that allow the nuclear function of MENT, namely, nuclear localization and DNA binding. However, the nuclear function of MENT is not restricted to the activities of the M-loop alone. In vitro, MENT brings about the dramatic remodeling of chromatin into higher-order structures by forming protein bridges via its reactive center loop. Further, we have determined that in a protease-mediated effect, DNA can act as a cofactor to accelerate the rate at which MENT can inhibit its target proteases. In this chapter, we discuss the isolation of MENT from native chicken blood as well as recombinant protein produced in Escherichia coli. Various techniques including in vitro functional assays and biophysical characterization are explained that can be used to elucidate the ability of the protein to interact with DNA and other deoxynucleoprotein complexes. In situ chromatin precipitation using natively purified MENT is also detailed. PMID- 22078530 TI - Solving serpin crystal structures. AB - Essentially the same steps are required to solve the crystal structure of a serpin as for any other protein: produce and purify protein, grow crystals, collect diffraction data, find estimates of the phase angles, and then refine and validate the structure. For the phasing step, experimental phasing methods involving heavy atom soaks were required for the first few structures, but with the large number of serpin structures now available, molecular replacement has become the method of choice. Two things are special about serpins. First, because of the central role of conformational change in serpin mechanism, it is advisable to consider a variety of molecular replacement models in different conformations and then to allow for rigid-body motions in the initial refinement steps. Second, probably owing to the flexibility of serpins, the average serpin crystal is significantly less well ordered than the average crystal of another protein, which increases the difficulty of solving and refining their structures. PMID- 22078531 TI - Crystallography of serpins and serpin complexes. AB - The serpin superfamily of protease inhibitors undergoes a remarkable conformational change to inhibit target proteases. To date, over 80 different serpin crystal structures have been determined. These data reveal that the serpin monomer can adopt five different conformations (native, partially inserted native, delta-form, latent, and cleaved). Further, recent studies have also revealed that serpins can domain swap; biochemical data suggest such an event underlies serpin polymerization in diseases such as antitrypsin deficiency. Here, we provide a comprehensive analysis on crystallization of serpins in context of the structural landscape of the serpin superfamily. PMID- 22078532 TI - Serpins as hormone carriers: modulation of release. AB - The hormone-carrying serpins, thyroxine- and corticosteroid-binding globulins, TBG and CBG, provide a clear example of the way the serpin conformational mechanism can be adapted not only to give an irreversible switching-off of function but also more significantly to allow a constant dynamic modulation of activity. This is illustrated here with the demonstration that hormone release from both TBG and CBG is responsive to changes in ambient temperature and specifically to changes in body temperature. An exception to this adaptation of the serpin mechanism is seen with another family member, angiotensinogen, in which hormone release is modulated by a redox switch and is apparently independent of changes in the serpin framework. PMID- 22078533 TI - Serpin-glycosaminoglycan interactions. AB - Serpins (serine protease inhibitors) have traditionally been grouped together based on structural homology. They share common structural features of primary sequence, but not all serpins require binding to cofactors in order to achieve maximal protease inhibition. In order to obtain physiologically relevant rates of inhibition of target proteases, some serpins utilize the unbranched sulfated polysaccharide chains known as glycosaminoglycans (GAGs) to enhance inhibition. These GAG-binding serpins include antithrombin (AT), heparin cofactor II (HCII), and protein C inhibitor (PCI). The GAGs heparin and heparan sulfate have been shown to bind AT, HCII, and PCI, while HCII is also able to utilize dermatan sulfate as a cofactor. Other serpins such as PAI-1, kallistatin, and alpha(1) antitrypsin also interact with GAGs with different endpoints, some accelerating protease inhibition while others inhibit it. There are many serpins that bind or carry ligands that are unrelated to GAGs, which are described elsewhere in this work. For most GAG-binding serpins, binding of the GAG occurs in a conserved region of the serpin near or involving helix D, with the exception of PCI, which utilizes helix H. The binding of GAG to serpin can lead to a conformational change within the serpin, which can lead to increased or tighter binding to the protease, and can accelerate the rates of inhibition up to 10,000-fold compared to the unbound native serpin. In this chapter, we will discuss three major GAG binding serpins with known physiological roles in modulating coagulation: AT (SERPINC1), HCII (SERPIND1), and PCI (SERPINA5). We will review methodologies implemented to study the structure of these serpins and those used to study their interactions with GAG's. We discuss novel techniques to examine the serpin-GAG interaction and finally we review the biological roles of these serpins by describing the mouse models used to study them. PMID- 22078534 TI - Targeting serpins in high-throughput and structure-based drug design. AB - Native, metastable serpins inherently tend to undergo stabilizing conformational transitions in mechanisms of health (e.g., enzyme inhibition) and disease (serpinopathies). This intrinsic tendency is modifiable by ligand binding, thus structure-based drug design is an attractive strategy in the serpinopathies. This can be viewed as a labor-intensive approach, and historically, its intellectual attractiveness has been tempered by relatively limited success in development of drugs reaching clinical practice. However, the increasing availability of a range of powerful experimental systems and higher-throughput techniques is causing academic and early-stage industrial pharmaceutical approaches to converge. In this review, we outline the different systems and techniques that are bridging the gap between what have traditionally been considered distinct disciplines. The individual methods are not serpin-specific. Indeed, many have only recently been applied to serpins, and thus investigators in other fields may have greater experience of their use to date. However, by presenting examples from our work and that of other investigators in the serpin field, we highlight how techniques with potential for automation and scaling can be combined to address a range of context-specific challenges in targeting the serpinopathies. PMID- 22078535 TI - Development of inhibitors of plasminogen activator inhibitor-1. AB - Plasminogen activator inhibitor-1 (PAI-1) belongs to the serine protease inhibitor super family (serpin) and is the primary inhibitor of both the tissue type (tPA) and urokinase-type (uPA) plasminogen activators. PAI-1 has been implicated in a wide range of pathological processes where it may play a direct role in a variety of diseases. These observations have made PAI-1 an attractive target for small molecule drug development. However, PAI-1's structural plasticity and its capacity to interact with multiple ligands have made the identification and development of such small molecule PAI-1 inactivating agents challenging. In the following pages, we discuss the difficulties associated with screening for small molecule inactivators of PAI-1, in particular, and of serpins, in general. We discuss strategies for high-throughput screening (HTS) of chemical and natural product libraries, and validation steps necessary to confirm identified hits. Finally, we describe steps essential to confirm specificity of active compounds, and strategies to examine potential mechanisms of compound action. PMID- 22078536 TI - Bioinformatic approaches for the identification of serpin genes with multiple reactive site loop coding exons. AB - In several branches of the tree of life, alternative splicing of a single primary transcript may give rise to multiple serpin isoforms exhibiting different target enzyme specificities. Though the continuously increasing number of genome sequencing projects has been paralleled by a rapidly rising number of serpin genes, the full spectrum of isoforms that some of these genes can encode has often not been recognized in routine database searches. In this chapter, we introduce procedures that enable the systematic extraction of multi-isoform generating serpin genes from genomic sequences. Spot checking of a model organism demonstrates that the phyletic distribution of such genes appears to be largely underestimated. The bioinformatic approach presented here may help to dissect the complete antiproteolytic spectrum of a genome's serpin complement and to register the occurrence of multitasking serpin genes in eukaryotes for functional and evolutionary studies. PMID- 22078537 TI - Methods to measure the kinetics of protease inhibition by serpins. AB - The serpin molecule has evolved an unusual mechanism of inhibition, involving an exposed reactive center loop (RCL) and conformational change to covalently trap a target protease. Successful inhibition of the protease is dependent on the rate of serpin-protease association and the efficiency with which the RCL inserts into beta-sheet A, translocating the covalently bound protease and thereby completing the inhibition process. This chapter describes the kinetic methods used for determining the rate of protease inhibition (k(a)) and the stoichiometry of inhibition. These kinetic variables provide a means to examine different serpin protease pairings, assess the effects of mutations within a serpin on protease inhibition, and determine the physiologically cognate protease of a serpin. PMID- 22078538 TI - Predicting serpin/protease interactions. AB - Proteases are tightly regulated by specific inhibitors, such as serpins, which are able to undergo considerable and irreversible conformational changes in order to trap their targets. There has been a considerable effort to investigate serpin structure and functions in the past few decades; however, the specific interactions between proteases and serpins remain elusive. In this chapter, we describe detailed experimental protocols to determine and characterize the extended substrate specificity of proteases based on a substrate phage display technique. We also describe how to employ a bioinformatics system to analyze the substrate specificity data obtained from this technique and predict the potential inhibitory serpin partners of a protease (in this case, the immune protease, granzyme B) in a step-by-step manner. The method described here could also be applied to other proteases for more generalized substrate specificity analysis and substrate discovery. PMID- 22078539 TI - Amino-Terminal Oriented Mass Spectrometry of Substrates (ATOMS) N-terminal sequencing of proteins and proteolytic cleavage sites by quantitative mass spectrometry. AB - Edman degradation is a long-established technique for N-terminal sequencing of proteins and cleavage fragments. However, for accurate data analysis and amino acid assignments, Edman sequencing proceeds on samples of single proteins only and so lacks high-throughput capabilities. We describe a new method for the high throughput determination of N-terminal sequences of multiple protein fragments in solution. Proteolytic processing can change the activity of bioactive proteins and also reveal cryptic binding sites and generate proteins with new functions (neoproteins) not found in the parent molecule. For example, extracellular matrix (ECM) protein processing often produces multiple proteolytic fragments with the generation of cryptic binding sites and neoproteins by ECM protein processing being well documented. The exact proteolytic cleavage sites need to be identified to fully understand the functions of the cleavage fragments and biological roles of proteases in vivo. However, the identification of cleavage sites in complex high molecular proteins such as those composing the ECM is not trivial. N terminal microsequencing of proteolytic fragments is the usual method employed, but it suffers from poor resolution of sodium dodecylsulfate-polyacrylamide gel electrophoresis gels and is inefficient at identifying multiple cleavages, requiring preparation of numerous gels or membrane slices for analysis. We recently developed Amino-Terminal Oriented Mass spectrometry of Substrates (ATOMS) to overcome these limitations as a complement for N-terminal sequencing. ATOMS employs isotopic labeling and quantitative tandem mass spectrometry to identify cleavage sites in a fast and accurate manner. We successfully used ATOMS to identify nearly 100 cleavage sites in the ECM proteins laminin and fibronectin. Presented herein is the detailed step-by-step protocol for ATOMS. PMID- 22078540 TI - Computational methods for studying serpin conformational change and structural plasticity. AB - Currently, over a hundred high-resolution structures of serpins are available, exhibiting a wide range of conformations. However, our understanding of serpin dynamics and conformational change is still limited, mainly due to challenges of monitoring structural changes and characterizing transient conformations using experimental methods. Insight can be provided, however, by employing theoretical and computational approaches. In this chapter, we present an overview of such methods, focusing on molecular dynamics and simulation. As serpin conformational dynamics span a wide range of timescales, we discuss the relative merits of each method and suggest which method is suited to specific conformational phenomena. PMID- 22078541 TI - Probing serpin conformational change using mass spectrometry and related methods. AB - The folding, misfolding, and inhibitory mechanisms of serpins are linked to both thermodynamic metastability and conformational flexibility. Characterizing the structural distribution of stability and flexibility in serpins in solution is challenging due to their large size and propensity for aggregation. Structural mass spectrometry techniques offer powerful tools for probing the mechanisms of serpin function and disfunction. In this chapter, we review the principles of the two most commonly employed structural mass spectrometry techniques- hydrogen/deuterium exchange and chemical footprinting--and describe their application to studying serpin flexibility, stability, and conformational change in solution. We also review the application of both hydrogen/deuterium exchange and ion mobility mass spectrometry to probe the mechanism of serpin polymerization and the structure of serpin polymers. PMID- 22078542 TI - Determining serpin conformational distributions with single molecule fluorescence. AB - Conformational plasticity is key to inhibitory serpin function, and this plasticity gives serpins relatively easy access to alternative, dysfunctional conformations. Thus, a given serpin population may contain both functional and dysfunctional proteins. Single molecule fluorescence (SMF), with its ability to interrogate one fluorescently labeled protein at a time, is a powerful method for elucidating conformational distributions and monitoring how these distributions change over time. SMF and related methods have been particularly valuable for characterizing serpin polymerization. Fluorescence correlation spectroscopy experiments have revealed a second lag phase during in vitro alpha(1)-antitrypsin polymerization associated with the formation of smaller oligomers that then condense to form longer polymers [Purkayastha, P., Klemke, J. W., Lavender, S., Oyola, R., Cooperman, B. S., and Gai, F. (2005). Alpha 1-antitrypsin polymerization: A fluorescence correlation spectroscopic study. Biochemistry44, 2642-2649.]. SMF studies of in vitro neuroserpin polymerization have confirmed that a monomeric intermediate is required for polymer formation while providing a test of proposed polymerization mechanisms [Chiou, A., Hagglof, P., Orte, A., Chen, A. Y., Dunne, P. D., Belorgey, D., Karlsson-Li, S., Lomas, D., and Klenerman, D. (2009). Probing neuroserpin polymerization and interaction with amyloid-beta peptides using single molecule fluorescence. Biophys. J.97, 2306 2315.]. SMF has also been used to monitor protease-serpin interactions. Single pair Forster resonance energy transfer studies of covalent protease-serpin complexes suggest that the extent of protease structural disruption in the complex is protease dependent [Liu, L., Mushero, N., Hedstrom, L., and Gershenson, A. (2006). Conformational distributions of protease-serpin complexes: A partially translocated complex. Biochemistry45, 10865-10872.]. SMF techniques are still evolving and the combination of SMF with encapsulation methods has the potential to provide more detailed information on the conformational changes associated with serpin polymerization, protease-serpin complex formation, and serpin folding. PMID- 22078543 TI - Serpin polymerization in vitro. AB - Serpin polymerization is an event which generally occurs within living tissue as a consequence of a folding defect caused by point mutations. Major advances in cell biology and imaging have allowed detailed studies into subcellular localization, processing, and clearance of serpin polymers, but to understand the molecular basis of the misfolded state and polymeric linkage, it has been and continues to be necessary to generate polymers in vitro. The goal of this chapter is to outline the principal techniques that have been developed over the past 20 years to produce and characterize serpin polymerization in vitro. For the majority of this time, all data were interpreted in accordance with the so-called "loop-sheet" hypothesis, where polymers form through the intermolecular incorporation of the reactive center loop (RCL) of one serpin monomer into the beta-sheet A of another. This hypothesis is supported by the ability of serpins to incorporate exogenous peptides into sheet A in an identical manner to the insertion of its own RCL upon cleavage by protease or conversion to the latent state. However, a recent crystal structure of an intact serpin dimer showed that much larger "domain swaps" are possible that would also lead to hyperstable linkage between serpin monomers. This chapter is therefore not limited to a description of experimental technique, but discusses the findings in light of the two current models of serpin polymerization. We would encourage readers to reevaluate the literature on serpin polymerization and to expand on the experiments outlined here in order to differentiate between possible domain swapping mechanisms. PMID- 22078545 TI - Serpin structure and evolution. Preface. PMID- 22078544 TI - The serpinopathies studying serpin polymerization in vivo. AB - The serpinopathies result from point mutations in members of the serine protease inhibitor or serpin superfamily. They are characterized by the formation of ordered polymers that are retained within the cell of synthesis. This causes disease by a "toxic gain of function" from the accumulated protein and a "loss of function" as a result of the deficiency of inhibitors that control important proteolytic cascades. The serpinopathies are exemplified by the Z (Glu342Lys) mutant of alpha1-antitrypsin that results in the retention of ordered polymers within the endoplasmic reticulum of hepatocytes. These polymers form the intracellular inclusions that are associated with neonatal hepatitis, cirrhosis, and hepatocellular carcinoma. A second example results from mutations in the neurone-specific serpin-neuroserpin to form ordered polymers that are retained as inclusions within subcortical neurones as Collins' bodies. These inclusions underlie the autosomal dominant dementia familial encephalopathy with neuroserpin inclusion bodies or FENIB. There are different pathways to polymer formation in vitro but not all form polymers that are relevant in vivo. It is therefore essential that protein-based structural studies are interpreted in the context of human samples and cell and animal models of disease. We describe here the biochemical techniques, monoclonal antibodies, cell biology, animal models, and stem cell technology that are useful to characterize the serpin polymers that form in vivo. PMID- 22078546 TI - [Population pharmacokinetics of gemcitabine applied to personalize the dosage used in cancer patients]. AB - OBJECTIVE: To develop and internally validate a population pharmacokinetic model for gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU); and to evaluate its predictive perfomance for personalizing the dosage used in cancer patients. METHODS: Gemcitabine and dFdU plasma concentrations were determined in 18 cancer patients. A 2-compartment pharmacokinetic model was implemented in the NONMEN VI program to determine the appropriate pharmacokinetic parameters. The power to identify the parameters was assessed by parametric bootstrap, and the internal model validation was performed using nonparametric bootstrap and visual and numerical predictive check methods. The final predictive performance of the model was assessed for accuracy and precision during the first (a priori) and second (a posteriori) chemotherapy cycles. RESULTS: The mean and interpatient variability of gemcitabine and dFdU clearance was 2.70 L/min (31.0%) and 0.0515 L/min (35.8%), respectively. The estimated distribution volume at steady state was 30 L for gemcitabine and 238 L for dFdU. Internal validation confirmed that the population pharmacokinetic model was appropriate for describing the plasma concentrations of gemcitabine and dFdU over time, as well as its variability in the study population. The accuracy and precision of a posteriori gemcitabine plasma concentrations improved by 67% and 46%, respectively, compared to the a priori prediction. CONCLUSION: The population pharmacokinetic model adequately characterised the gemcitabine and dFdU plasma concentrations in the study population over time, and can be used to accurately and precisely optimise gemcitabine dosing regimens in cancer patients. PMID- 22078547 TI - Concentrations of organochlorine pesticides and polychlorinated biphenyls in human serum and adipose tissue from Bolivia. AB - Organochlorine pesticides and polychlorinated biphenyls (PCBs) are synthetic chemicals that are highly resistant to biodegradation and have proven adverse health effects. The objectives of this study were to determine concentrations of three selected organochlorine pesticides (p,p'-DDT, p,p'-DDE, HCB) and three specific PCB congeners (PCB 138, 153, 180) in adipose tissue and serum samples from an urban adult population (n=112) in the city of Santa Cruz de la Sierra, Bolivia, and to investigate their relationships within and between the two matrices and with selected socio-demographic characteristics. The percentages of samples positive for these compounds ranged from 40% for PCB 180 to 100% for p,p' DDE in adipose tissue, and from 21% for HCB to 93% for p,p'-DDE in serum. Median number of residues per sample was five for adipose tissue and three for serum. Geometric mean concentrations indicate a considerable historical and recent exposure to organochlorine pesticides and PCBs in this population. Adipose tissue:serum ratios ranged from 149.3 to 590.3 (wet basis) and from 0.9 to 3.5 (lipid basis). We found positive and statistically significant correlations between adipose tissue and serum concentrations only in p,p'-DDE and HCB. This novel study in Bolivia underlines the need for human biomonitoring to assess exposure to environmental pollutants in South America. PMID- 22078548 TI - Phenotypic and molecular characterization of serogroup C Neisseria meningitidis associated with an outbreak in Bahia, Brazil. AB - OBJECTIVE: To characterize meningococcal strains isolated from five cases of meningococcal disease (MD) associated with an outbreak in Trancoso - BA, occurred in October 2009. All cases, with the exception of a 39-year-old male, attended a dance party with approximately 1000 youngsters in a rural site. MATERIALS AND METHODS: The epidemiological investigation was conducted by the Epidemiological Surveillance Service of Bahia State. Meningococcal strains were characterized at Adolfo Lutz Institute, the Brazilian National Reference Laboratory for Bacterial Meningitis by conventional techniques (serotype, serosubtype and antimicrobial susceptibility test) and by molecular methods (Pulsed-field gel electrophoresis - PFGE and Multilocus Sequence Typing - MLST). RESULTS: The PFGE showed 2 closely related restriction profiles, designated as PFGE types A and A1, having 92% relatedness to each other. MLST characterization showed both A and A1 clones were ST-3780, which belongs to the ST-103 complex. All isolates displayed the phenotype C:23:P1.5 and were susceptible to all antibiotics tested. CONCLUSIONS: This is the first reported MD outbreak associated with serogroup C ST-103 complex in Brazil, as well as the party and illicit drug-use associated outbreak. PMID- 22078549 TI - Differential Gene Expression to Investigate the Effects of Low-level Electrochemical Currents on Bacillus subtilis. AB - With the emergence and spread of multidrug resistant bacteria, effective methods to eliminate both planktonic bacteria and those embedded in surface-attached biofilms are needed. Electric currents at MUA-mA/cm2 range are known to reduce the viability of bacteria. However, the mechanism of such effects is still not well understood. In this study, Bacillus subtilis was used as the model Gram positive species to systematically investigate the effects of electrochemical currents on bacteria including the morphology, viability, and gene expression of planktonic cells, and viability of biofilm cells. The data suggest that weak electrochemical currents can effectively eliminate B. subtilis both as planktonic cells and in biofilms. DNA microarray results indicate that the genes associated with oxidative stress response, nutrient starvation, and membrane functions were induced by electrochemical currents. These findings suggest that ions and oxidative species generated by electrochemical reactions might be important for the killing effects of these currents. PMID- 22078550 TI - Cutting-hedge research into bacterial invasion. AB - Glycoside hydrolases are the tools that pathogenic bacteria use to cut through the defensive glycan structure on host cell surfaces. In this issue of Structure, Pluvinage et al. (2011) report how a bacterial polypeptide with more than one hydrolase module broadens the effective substrate specificity. PMID- 22078551 TI - Fibrinogen unfolding mechanisms are not too much of a stretch. AB - Molecular explanations for the extraordinary elasticity and extensibility of fibrin fibers are still lacking. Now, Zhmurov et al. (2011) use force spectroscopy experiments, and innovative simulations that match the time and force scales of these experiments, to study fibrinogen behavior under an applied force providing deeper insights into this process. PMID- 22078552 TI - Tackling the legs of mannan-binding lectin. AB - The recognition of pathogen surfaces by mannan-binding lectin activates MASP proteases, leading to complement activation. A crystal structure by Gingras et al. (2011) in this issue of Structure now shows how the collagen-like stems of mannan-binding lectin bind MASP-1 through a minimalist set of interactions. PMID- 22078553 TI - Type II ABC permeases: are they really so different? AB - Structural and biochemical data reported by Tirado-Lee et al. (2011) in this issue of Structure reveal the existence of high and low affinity ABC transporters for the same substrate in a single organism, thus raising questions about structural and mechanistic differences within the ABC superfamily. PMID- 22078554 TI - Cell membranes: the lipid perspective. AB - Although cell membranes are packed with proteins mingling with lipids, remarkably little is known about how proteins interact with lipids to carry out their function. Novel analytical tools are revealing the astounding diversity of lipids in membranes. The issue is now to understand the cellular functions of this complexity. In this Perspective, we focus on the interface of integral transmembrane proteins and membrane lipids in eukaryotic cells. Clarifying how proteins and lipids interact with each other will be important for unraveling membrane protein structure and function. Progress toward this goal will be promoted by increasing overlap between different fields that have so far operated without much crosstalk. PMID- 22078555 TI - Toward the fourth dimension of membrane protein structure: insight into dynamics from spin-labeling EPR spectroscopy. AB - Trapping membrane proteins in the confines of a crystal lattice obscures dynamic modes essential for interconversion between multiple conformations in the functional cycle. Moreover, lattice forces could conspire with detergent solubilization to stabilize a minor conformer in an ensemble thus confounding mechanistic interpretation. Spin labeling in conjunction with electron paramagnetic resonance (EPR) spectroscopy offers an exquisite window into membrane protein dynamics in the native-like environment of a lipid bilayer. Systematic application of spin labeling and EPR identifies sequence-specific secondary structures, defines their topology and their packing in the tertiary fold. Long range distance measurements (60 A-80 A) between pairs of spin labels enable quantitative analysis of equilibrium dynamics and triggered conformational changes. This review highlights the contribution of spin labeling to bridging structure and mechanism. Efforts to develop methods for determining structures from EPR restraints and to increase sensitivity and throughput promise to expand spin labeling applications in membrane protein structural biology. PMID- 22078556 TI - Molecular simulation approaches to membrane proteins. AB - Molecular simulations are an invaluable tool for understanding membrane proteins. Improvements to both hardware and simulation methods have allowed access to physiologically relevant timescales and have permitted the simulation of large multimeric complexes. This, coupled to the recent expansion in membrane protein structures, provides a means to elucidate the relationship between protein structure and function. In this review, we discuss the progress in using simulations to understand the complex processes that occur at the boundary of a cell, ranging from the transport of solutes and the interactions of ligands with ion channels to the conformational rearrangements required for gating of channels and the signaling by membrane-associated complexes. PMID- 22078558 TI - Identifying conformational states of macromolecules by eigen-analysis of resampled cryo-EM images. AB - We present the codimensional principal component analysis (PCA), a novel and straightforward method for resolving sample heterogeneity within a set of cryo-EM 2D projection images of macromolecular assemblies. The method employs PCA of resampled 3D structures computed using subsets of 2D data obtained with a novel hypergeometric sampling scheme. PCA provides us with a small subset of dominating "eigenvolumes" of the system, whose reprojections are compared with experimental projection data to yield their factorial coordinates constructed in a common framework of the 3D space of the macromolecule. Codimensional PCA is unique in the dramatic reduction of dimensionality of the problem, which facilitates rapid determination of both the plausible number of conformers in the sample and their 3D structures. We applied the codimensional PCA to a complex data set of Thermus thermophilus 70S ribosome, and we identified four major conformational states and visualized high mobility of the stalk base region. PMID- 22078557 TI - Direct visualization of HIV-1 with correlative live-cell microscopy and cryo electron tomography. AB - Cryo-electron tomography (cryoET) allows 3D visualization of cellular structures at molecular resolution in a close-to-native state and therefore has the potential to help elucidate early events of HIV-1 infection in host cells. However, structural details of infecting HIV-1 have not been observed, due to technological challenges in working with rare and dynamic HIV-1 particles in human cells. Here, we report structural analysis of HIV-1 and host-cell interactions by means of a correlative high-speed 3D live-cell-imaging and cryoET method. Using this method, we showed under near-native conditions that intact hyperstable mutant HIV-1 cores are released into the cytoplasm of host cells. We further obtained direct evidence to suggest that a hyperstable mutant capsid, E45A, showed delayed capsid disassembly compared to the wild-type capsid. Together, these results demonstrate the advantages of our correlative live-cell and cryoET approach for imaging dynamic processes, such as viral infection. PMID- 22078559 TI - Crystal structure of human Mre11: understanding tumorigenic mutations. AB - Mre11 plays an important role in repairing damaged DNA by cleaving broken ends and by providing a platform for other DNA repair proteins. Various Mre11 mutations have been identified in several types of cancer. We have determined the crystal structure of the human Mre11 core (hMre11), which contains the nuclease and capping domains. hMre11 dimerizes through the interfaces between loop beta3 alpha3 from one Mre11 and loop beta4-beta5 from another Mre11, and between loop alpha2-beta3 from one Mre11 and helices alpha2 and alpha3 from another Mre11, and assembles into a completely different dimeric architecture compared with bacterial or archaeal Mre11 homologs. Nbs1 binds to the region containing loop alpha2-beta3 which participates in dimerization. The hMre11 structure in conjunction with biochemical analyses reveals that many tumorigenic mutations are primarily associated with Nbs1 binding and partly with nuclease activities, providing a framework for understanding how mutations inactivate Mre11. PMID- 22078560 TI - Inhibition of the pneumococcal virulence factor StrH and molecular insights into N-glycan recognition and hydrolysis. AB - The complete degradation of N-linked glycans by the pathogenic bacterium Streptococcus pneumoniae is facilitated by the large multimodular cell wall attached exo-beta-D-N-acetylglucosaminidase StrH. Structural dissection of this virulence factor using X-ray crystallography showed it to have two structurally related glycoside hydrolase family 20 catalytic domains, which displayed the expected specificity for complex N-glycans terminating in N-acetylglucosamine but exhibited unexpected differences in their preferences for the substructures present in these glycans. The structures of the two catalytic domains in complex with unhydrolyzed substrates, including an N-glycan possessing a bisecting N acetylglucosamine residue, revealed the specific architectural features in the active sites that confer their differential specificities. Inhibitors of StrH are demonstrated to be effective tools in modulating the interaction of StrH with components of the host, such as the innate immune system. Overall, new structural and functional insight into a carbohydrate-mediated component of the pneumococcus host interaction is provided. PMID- 22078561 TI - Mechanism of fibrin(ogen) forced unfolding. AB - Fibrinogen, upon enzymatic conversion to monomeric fibrin, provides the building blocks for fibrin polymer, the scaffold of blood clots and thrombi. Little has been known about the force-induced unfolding of fibrin(ogen), even though it is the foundation for the mechanical and rheological properties of fibrin, which are essential for hemostasis. We determined mechanisms and mapped the free energy landscape of the elongation of fibrin(ogen) monomers and oligomers through combined experimental and theoretical studies of the nanomechanical properties of fibrin(ogen), using atomic force microscopy-based single-molecule unfolding and simulations in the experimentally relevant timescale. We have found that mechanical unraveling of fibrin(ogen) is determined by the combined molecular transitions that couple stepwise unfolding of the gamma chain nodules and reversible extension-contraction of the alpha-helical coiled-coil connectors. These findings provide important characteristics of the fibrin(ogen) nanomechanics necessary to understand the molecular origins of fibrin viscoelasticity at the fiber and whole clot levels. PMID- 22078562 TI - Structural basis of mannan-binding lectin recognition by its associated serine protease MASP-1: implications for complement activation. AB - Complement activation contributes directly to health and disease. It neutralizes pathogens and stimulates immune processes. Defects lead to immunodeficiency and autoimmune diseases, whereas inappropriate activation causes self-damage. In the lectin and classical pathways, complement is triggered upon recognition of a pathogen by an activating complex. Here we present the first structure of such a complex in the form of the collagen-like domain of mannan-binding lectin (MBL) and the binding domain of its associated protease (MASP-1/-3). The collagen binds within a groove using a pivotal lysine side chain that interacts with Ca(2+) coordinating residues, revealing the essential role of Ca(2+). This mode of binding is prototypic for all activating complexes of the lectin and classical pathways, and suggests a general mechanism for the global changes that drive activation. The structural insights reveal a new focus for inhibitors and we have validated this concept by targeting the binding pocket of the MASP. PMID- 22078563 TI - Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein. AB - Human glycolipid transfer protein (GLTP) fold represents a novel structural motif for lipid binding/transfer and reversible membrane translocation. GLTPs transfer glycosphingolipids (GSLs) that are key regulators of cell growth, division, surface adhesion, and neurodevelopment. Herein, we report structure-guided engineering of the lipid binding features of GLTP. New crystal structures of wild type GLTP and two mutants (D48V and A47D||D48V), each containing bound N nervonoyl-sulfatide, reveal the molecular basis for selective anchoring of sulfatide (3-O-sulfo-galactosylceramide) by D48V-GLTP. Directed point mutations of "portal entrance" residues, A47 and D48, reversibly regulate sphingosine access to the hydrophobic pocket via a mechanism that could involve homodimerization. "Door-opening" conformational changes by phenylalanines within the hydrophobic pocket are revealed during lipid encapsulation by new crystal structures of bona fide apo-GLTP and GLTP complexed with N-oleoyl glucosylceramide. The development of "engineered GLTPs" with enhanced specificity for select GSLs provides a potential new therapeutic approach for targeting GSL mediated pathologies. PMID- 22078564 TI - Structural investigation of rimantadine inhibition of the AM2-BM2 chimera channel of influenza viruses. AB - The M2 channel of influenza A is a target of the adamantane family antiviral drugs. Two different drug-binding sites have been reported: one inside the pore, and the other is a lipid-facing pocket. A previous study showed that a chimera of M2 variants from influenza A and B that contains only the pore-binding site is sensitive to amantadine inhibition, suggesting that the primary site of inhibition is inside the pore. To obtain atomic details of channel-drug interaction, we determined the structures of the chimeric channel with and without rimantadine. Inside the channel and near the N-terminal end, methyl groups of Val27 and Ala30 from four subunits form a hydrophobic pocket around the adamantane, and the drug amino group appears to be in polar contact with the backbone oxygen of Ala30. The structures also reveal differences between the drug bound and -unbound states of the channel that can explain drug resistance. PMID- 22078565 TI - Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is crucial for its regulation of integrin activation. AB - Kindlin-2 belongs to an emerging class of regulators for heterodimeric (alpha/beta) integrin adhesion receptors. By binding to integrin beta cytoplasmic tail via its C-terminal FERM-like domain, kindlin-2 promotes integrin activation. Intriguingly, this activation process depends on the N terminus of kindlin-2 (K2 N) that precedes the FERM domain. The molecular function of K2-N is unclear. We present the solution structure of K2-N, which displays a ubiquitin fold similar to that observed in kindlin-1. Using chemical shift mapping and mutagenesis, we found that K2-N contains a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5) bisphosphate. We show that while wild-type kindlin-2 is capable of promoting integrin activation, such ability is significantly reduced for its membrane binding defective mutant. These data suggest a membrane-binding function of the ubiquitin-like domain of kindlin-2, which is likely common for all kindlins to promote their localization to the plasma membrane and control integrin activation. PMID- 22078566 TI - Structural insights into Ail-mediated adhesion in Yersinia pestis. AB - Ail is an outer membrane protein from Yersinia pestis that is highly expressed in a rodent model of bubonic plague, making it a good candidate for vaccine development. Ail is important for attaching to host cells and evading host immune responses, facilitating rapid progression of a plague infection. Binding to host cells is important for injection of cytotoxic Yersinia outer proteins. To learn more about how Ail mediates adhesion, we solved two high-resolution crystal structures of Ail, with no ligand bound and in complex with a heparin analog called sucrose octasulfate. We identified multiple adhesion targets, including laminin and heparin, and showed that a 40 kDa domain of laminin called LG4-5 specifically binds to Ail. We also evaluated the contribution of laminin to delivery of Yops to HEp-2 cells. This work constitutes a structural description of how a bacterial outer membrane protein uses a multivalent approach to bind host cells. PMID- 22078568 TI - Classification of a Haemophilus influenzae ABC transporter HI1470/71 through its cognate molybdate periplasmic binding protein, MolA. AB - molA (HI1472) from H. influenzae encodes a periplasmic binding protein (PBP) that delivers substrate to the ABC transporter MolB(2)C(2) (formerly HI1470/71). The structures of MolA with molybdate and tungstate in the binding pocket were solved to 1.6 and 1.7 A resolution, respectively. The MolA-binding protein binds molybdate and tungstate, but not other oxyanions such as sulfate and phosphate, making it the first class III molybdate-binding protein structurally solved. The ~100 MUM binding affinity for tungstate and molybdate is significantly lower than observed for the class II ModA molybdate-binding proteins that have nanomolar to low micromolar affinity for molybdate. The presence of two molybdate loci in H. influenzae suggests multiple transport systems for one substrate, with molABC constituting a low-affinity molybdate locus. PMID- 22078567 TI - Structural basis for MU-opioid receptor binding and activation. AB - Opioids that stimulate the MU-opioid receptor (MOR1) are the most frequently prescribed and effective analgesics. Here we present a structural model of MOR1. Molecular dynamics simulations show a ligand-dependent increase in the conformational flexibility of the third intracellular loop that couples with the G protein complex. These simulations likewise identified residues that form frequent contacts with ligands. We validated the binding residues using site directed mutagenesis coupled with radioligand binding and functional assays. The model was used to blindly screen a library of ~1.2 million compounds. From the 34 compounds predicted to be strong binders, the top three candidates were examined using biochemical assays. One compound showed high efficacy and potency. Post hoc testing revealed this compound to be nalmefene, a potent clinically used antagonist, thus further validating the model. In summary, the MOR1 model provides a tool for elucidating the structural mechanism of ligand-initiated cell signaling and for screening novel analgesics. PMID- 22078569 TI - A conformational switch in the CRIB-PDZ module of Par-6. AB - Here, we report a novel mechanism of PDZ (PSD-95/Dlg/ZO-1) domain regulation that distorts a conserved element of PDZ ligand recognition. The polarity regulator Par-6 assembles a conserved multiprotein complex and is directly modulated by the Rho GTPase Cdc42. Cdc42 binds the adjacent Cdc42/Rac interactive binding (CRIB) and PDZ domains of Par-6, increasing C-terminal ligand binding affinity by 10 fold. By solving structures of the isolated PDZ domain and a disulfide-stabilized CRIB-PDZ, we detected a conformational switch that controls affinity by altering the configuration of the conserved "GLGF" loop. As a result, lysine 165 is displaced from the PDZ core by an adjacent hydrophobic residue, disrupting coordination of the PDZ ligand-binding cleft. Stabilization of the CRIB:PDZ interface restores K165 to its canonical location in the binding pocket. We conclude that a unique "dipeptide switch" in the Par-6 PDZ transmits a signal for allosteric activation to the ligand-binding pocket. PMID- 22078570 TI - Improving blood safety and patient outcomes with pathogen reduction technology. PMID- 22078571 TI - Heterogeneous telomere defects in patients with severe forms of dyskeratosis congenita. AB - BACKGROUND: Telomeres represent the tips of linear chromosomes. In human subjects telomere maintenance deficiency leads to dyskeratosis congenita (DC), a rare genetic disorder characterized by progressive bone marrow failure, accelerated aging, and cancer predisposition. Hoyeraal-Hreidarsson syndrome (HH) is a severe variant of DC in which an early onset of bone marrow failure leading to combined immunodeficiency is associated with microcephaly, cerebellar hypoplasia, and growth retardation. OBJECTIVES: Limited information is available on the cellular and molecular phenotypes of cells from patients with HH. We analyzed fibroblasts and whole blood cells from 5 patients with HH, 3 of them of unknown molecular origin. METHODS: Telomere length, cellular senescence rate, telomerase activity, telomeric aberration, and DNA repair pathways were investigated. RESULTS: Although patients' cells exhibit dysfunctional telomeres, sharp differences in the telomeric aberrations and telomere lengths were noted among these patients. In some patients the dysfunctional telomere phenotype was unprecedented and associated with either normal telomere length or with telomeric aberrations akin to fragile telomeres. This result is of particular importance because the molecular diagnosis of these patients is primarily based on telomere length, which therefore misses a subset of patients with telomere dysfunction. CONCLUSION: These observations provide the notions that (1) various telomere defects can lead to similar clinical features, (2) telomere dysfunction in cells from patients with DC/HH is not always associated with short telomeres, and (3) additional factors, likely involved in telomere protection rather than in length regulation, are responsible for a subset of DC/HH. PMID- 22078572 TI - A rapid screening method to detect autosomal-dominant ectodermal dysplasia with immune deficiency syndrome. PMID- 22078573 TI - Effect of Lactobacillus GG on tolerance acquisition in infants with cow's milk allergy: a randomized trial. PMID- 22078574 TI - CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease. AB - BACKGROUND: Based on their potency to control allergic diseases, regulatory T (Treg) cells represent a promising target for novel strategies to interfere with allergic airway inflammation. We have previously demonstrated that stimulation of the CD4 molecule on human Treg cells activates their suppressive activity in vitro and in vivo. OBJECTIVE: We sought to determine the effect of CD4-mediated Treg-cell activation on pulmonary inflammation in a humanized mouse model of allergic airway inflammation. METHODS: PBMCs obtained from donors allergic to birch pollen or from healthy donors were injected into NOD-severe combined immunodeficiency gammac(-/-) mice, followed by allergen airway challenges and analysis of airway responsiveness and inflammation. For Treg-cell activation, mice were treated with the CD4-binding, lck-activating recombinant HIV-1 surface protein gp120 after sensitization prior to allergen challenge. Control experiments with CD25-depleted PBMCs were performed to evaluate the role of Treg cells. RESULTS: PBMCs from allergic donors but not from healthy donors induced airway inflammation and airway hyperresponsiveness. Treatment with gp120 prior to allergen challenge abrogated airway hyperresponsiveness and reduced the inflammatory immune response. In contrast, treatment had no effect on inflammation and airway hyperresponsiveness in mice that received CD25-depleted PBMCs, demonstrating Treg-cell dependency of disease prevention. CONCLUSION: Allergic airway inflammation can be prevented by stimulation of human Treg cells by CD4. These results suggest a clinical potential of Treg-cell activation by high-affinity CD4 ligands in allergic diseases. PMID- 22078575 TI - Generalized linear mixed model for segregation distortion analysis. AB - BACKGROUND: Segregation distortion is a phenomenon that the observed genotypic frequencies of a locus fall outside the expected Mendelian segregation ratio. The main cause of segregation distortion is viability selection on linked marker loci. These viability selection loci can be mapped using genome-wide marker information. RESULTS: We developed a generalized linear mixed model (GLMM) under the liability model to jointly map all viability selection loci of the genome. Using a hierarchical generalized linear mixed model, we can handle the number of loci several times larger than the sample size. We used a dataset from an F(2) mouse family derived from the cross of two inbred lines to test the model and detected a major segregation distortion locus contributing 75% of the variance of the underlying liability. Replicated simulation experiments confirm that the power of viability locus detection is high and the false positive rate is low. CONCLUSIONS: Not only can the method be used to detect segregation distortion loci, but also used for mapping quantitative trait loci of disease traits using case only data in humans and selected populations in plants and animals. PMID- 22078576 TI - Reliability analysis for a proposed critical appraisal tool demonstrated value for diverse research designs. AB - OBJECTIVE: To examine the reliability of scores obtained from a proposed critical appraisal tool (CAT). STUDY DESIGN AND SETTING: Based on a random sample of 24 health-related research papers, the scores from the proposed CAT were examined using intraclass correlation coefficients (ICCs), generalizability theory, and participants' feedback. RESULTS: The ICC for all research papers was 0.83 (consistency) and 0.74 (absolute agreement) for four participants. For individual research designs, the highest ICC (consistency) was for qualitative research (0.91) and the lowest was for descriptive, exploratory and observational research (0.64). The G study showed a moderate research design effect (32%) for scores averaged across all papers. The research design effect was mainly in the Sampling, Results, and Discussion categories (44%, 36%, and 34%, respectively). The scores for research designs showed a majority paper effect for each (53-70%), with small to moderate rater or paper*rater interaction effects (0-27%). CONCLUSIONS: Possible reasons for the research design effect were that the participants were unfamiliar with some of the research designs and that papers were not matched to participants' expertise. Even so, the proposed CAT showed great promise as a tool that can be used across a wide range of research designs. PMID- 22078577 TI - Re: ICUD-EAU International Consultation on Kidney Cancer 2010: Treatment of metastatic disease. PMID- 22078578 TI - Re: The impact of targeted molecular therapies on the level of renal cell carcinoma vena caval tumor thrombus. PMID- 22078579 TI - Re: Safety of presurgical targeted therapy in the setting of metastatic renal cell carcinoma. PMID- 22078580 TI - Re: Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma. PMID- 22078582 TI - Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort. PMID- 22078583 TI - Vascular endothelial growth factor-C associated with computed tomography used in the diagnosis of lymph node metastasis of bladder carcinoma. PMID- 22078584 TI - Re: Abiraterone and increased survival in metastatic prostate cancer. PMID- 22078585 TI - Re: Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. PMID- 22078586 TI - Re: Management of seminomatous testicular cancer: a binational prospective population-based study from the Swedish Norwegian testicular cancer study group. PMID- 22078587 TI - Re: A clinically relevant approach to imaging prostate cancer: review. PMID- 22078588 TI - Re: Depressive disorders and panic attacks in women with bladder pain syndrome/interstitial cystitis: a population-based sample. PMID- 22078589 TI - Re: Genitourinary infections after a routine pelvic exam. PMID- 22078590 TI - Re: Normalization of proliferation and tight junction formation in bladder epithelial cells from patients with interstitial cystitis/painful bladder syndrome by d-proline and d-pipecolic acid derivatives of antiproliferative factor. PMID- 22078591 TI - Re: Bladder pain syndrome treated with triple therapy with gabapentin, amitriptyline, and a nonsteroidal anti-inflammatory drug. PMID- 22078592 TI - Re: Evaluating an evidence-based bundle for preventing surgical site infection: a randomized trial. PMID- 22078593 TI - Re: Microperforations of surgical gloves in urology: minimally invasive versus open surgeries. PMID- 22078594 TI - Re: Body mass index and the risk of infections in institutionalised geriatric patients. PMID- 22078595 TI - Re: Urine cultures from indwelling bladder catheters in nursing home patients: a point prevalence study in a Swedish county. PMID- 22078600 TI - Re: Does timing of presentation of penile fracture affect outcome of surgical intervention? PMID- 22078599 TI - Re: The use of penile skin graft versus penile skin flap in the repair of long bulbo-penile urethral stricture: a prospective randomized study. PMID- 22078601 TI - Re: Penile implant utilization following treatment for prostate cancer: analysis of the SEER-Medicare database. PMID- 22078602 TI - Re: Intra-abdominal reservoir placement during penile prosthesis surgery in post robotically assisted laparoscopic radical prostatectomy patients: a case report and practical considerations. PMID- 22078603 TI - Re: Effective surgical safety checklist implementation. PMID- 22078604 TI - Re: Preoperative risk factors for postoperative delirium (POD) after urological surgery in the elderly. PMID- 22078605 TI - Re: Management of rectal injury during robotic radical prostatectomy. PMID- 22078606 TI - Re: Factors affecting recovery of functional status in older adults after cancer surgery. PMID- 22078607 TI - Re: Accumulated frailty characteristics predict postoperative discharge institutionalization in the geriatric patient. PMID- 22078608 TI - Re: Readmissions in the postoperative period following urinary diversion. PMID- 22078610 TI - Re: The diagnostic value of abdominal ultrasound, urine cytology and prostate specific antigen testing in the lower urinary tract symptoms clinic. PMID- 22078612 TI - Re: Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post-transplant outcomes. PMID- 22078611 TI - Re: Mortality trends for benign prostatic hyperplasia and prostate cancer in English populations 1979-2006. PMID- 22078613 TI - Re: Risk of window period HIV infection in high infectious risk donors: systematic review and meta-analysis. PMID- 22078614 TI - Re: Ex-vivo ureteroscopy at the time of live donor nephrectomy. PMID- 22078615 TI - Re: Native nephrectomy for renal cell carcinoma in transplant recipients. PMID- 22078616 TI - Re: Validating the patient safety indicators in the Veterans Health Administration: are they ready for prime time? PMID- 22078617 TI - Re: Assessment of quality of cancer-related follow-up care from the cancer survivor's perspective. PMID- 22078618 TI - Re: Perioperative surgical findings in congenital and acquired undescended testis. PMID- 22078619 TI - Re: Outcomes of scrotal exploration for acute scrotal pain suspicious of testicular torsion: a consecutive case series of 173 patients. PMID- 22078621 TI - Re: Are antibiotics necessary for pediatric epididymitis? PMID- 22078620 TI - Re: The Cleveland Clinic experience with adult hypospadias patients undergoing repair: their presentation and a new classification system. PMID- 22078622 TI - Re: Reduction of plasma oxalate levels by oral application of Oxalobacter formigenes in 2 patients with infantile oxalosis. PMID- 22078624 TI - Re: Role of autonomous androgen receptor signaling in prostate cancer initiation is dichotomous and depends on the oncogenic signal. PMID- 22078625 TI - Re: Differential transformation capacity of Src family kinases during the initiation of prostate cancer. PMID- 22078626 TI - Re: The cancer/testis antigen prostate-associated gene 4 (PAGE4) is a highly intrinsically disordered protein. PMID- 22078627 TI - Re: Developmental control of apoptosis by the immunophilin aryl hydrocarbon receptor-interacting protein (AIP) involves mitochondrial import of the survivin protein. PMID- 22078628 TI - Re: Pioglitazone attenuates prostatic enlargement in diet-induced insulin resistant rats by altering lipid distribution and hyperinsulinaemia. PMID- 22078629 TI - A successful approach to long-acting contraceptive implants in primary care. AB - BACKGROUND: Subdermal implants of etonogestrol are an effective method of contraception but have a high discontinuation rate often due to irregular uterine bleeding. Implants are often placed in specialist environments away from the woman's usual primary health care provider in the UK. STUDY DESIGN: The aim of the study was to assess the rate of (and reasons for) discontinuation of the implant using a two-stage procedure for device placement in primary care. RESULTS: One hundred thirty-one implants were placed between July 2005 and September 2009. Follow-up was complete at 9th November 2010, with the exception of seven women who left the practice area. The median age at placement was 24.0 years (interquartile range, 18.0-32.8 years). At 1 year, 90% of implants were still in place. Twelve implants (10%) were removed: seven were for irregular bleeding, three were for weight gain and one each was for acne and wishing to conceive. Over the next year, a further nine were removed (three for irregular bleeding, one to conceive and one each for acne, low mood, abdominal pain and amenorrhea). Two more were removed at 25 and 27 months (both for irregular bleeding), with no further implants removed thereafter other than to exchange for a new implant at 36 months. There were no pregnancies in 3595 women-months. CONCLUSIONS: Etonogestrel implants can be safely and successfully inserted in primary care by well-trained users. It is possible for well-trained users to achieve a very high device retention rate in primary care compared with published data from other practice settings. PMID- 22078630 TI - When did family planning become a risky proposition? PMID- 22078631 TI - Evaluation of oxidative stress after treatment with low estrogen contraceptive either alone or associated with specific antioxidant therapy. AB - BACKGROUND: The aim of the study is to analyze the effect of low estrogen contraceptives (OC) on oxidative stress (OS) and concomitantly also the changes produced by different treatments using physiological modulators (PMs) with antioxidant action. STUDY DESIGN: Sixty-four female volunteers using a low estrogen OC regimen were analyzed for their OS status through the reactive oxygen metabolites-derived compounds (d-ROMs) test, during 5 different cycles (Cycle I to V). Three experiments were performed. RESULTS: In the first experiment (Cycle I), OS showed almost a constant 50% increase in all the determinations. In the second experiment (Cycles II and III), the participants were divided into two groups and treated double-blind with a placebo or with a PM (MF Templar(r)) that significantly reduced OS, on average by 69%, while the placebo had no effect. In the third experiment (Cycles IV and V), the placebo group was divided into three subgroups, A, B, C and treated, respectively, with MF Templar(r), green tea containing the same amount of catechins present in MF Templar(r) or with MF Templar(r) devoid of catechins. Only the complete product, MF Templar(r), was able to reduce OS levels, on average by 70%. CONCLUSION: We conclude that to control the OS generated by OC, specific types of PMs are needed. In particular MF Templar(r) was able to induce a significant reduction of OS levels. PMID- 22078632 TI - The effect of obesity and low-dose oral contraceptives on carbohydrate and lipid metabolism. AB - BACKGROUND: Combination oral contraceptives (OCs) have little effect on carbohydrate and lipid metabolism in normal-weight women. Based on lack of change in intermediate markers, as well as results of epidemiologic studies, low-dose OCs do not increase the risk of diabetes or cardiovascular disease. Obesity is a risk factor for impaired glucose tolerance, diabetes and coronary artery disease, and most previous OC studies excluded these women; thus, we have limited information about carbohydrate and lipid metabolism in obese OC users. STUDY DESIGN: This study compared changes in carbohydrate and lipid parameters in 71 normal-weight and 38 obese women initiating the OC. Women were randomized to two pills: 30 mcg ethinyl estradiol (EE)/150 mcg levonorgestrel (LNG) or 20 mcg EE/100 mcg LNG. Participants underwent baseline and cycle-3 measurements of fasting serum glucose; insulin; triglycerides and total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. RESULTS: Normal-weight and obese participants experienced similar changes in mean glucose, insulin and log homeostatic model assessment, as well as similar changes in total cholesterol, HDL and triglycerides; however, change in mean LDL (-4.9+/-20.6 mg/dL vs. +3.8+/ 17.3 mg/dL) was different between the obese and normal-weight groups, respectively. Among the obese participants, change in glucose was marginally greater with the higher dose pill (p=.06); otherwise, changes between the body mass index groups were not modified by pill dose. CONCLUSIONS: Obesity had little effect on any OC-induced changes in carbohydrate or lipid metabolism except for a borderline adverse interaction between obesity and OC dose with respect to fasting glucose and a positive interaction between obesity and OC use with respect to LDL cholesterol. PMID- 22078633 TI - Cytokine & chemokine response in the lungs, pleural fluid and serum in thoracic surgery using one-lung ventilation. AB - BACKGROUND: Thoracic surgery mandates usually a one-lung ventilation (OLV) strategy with the collapse of the operated lung and ventilation of the non operated lung. These procedures trigger a substantial inflammatory response. The aim of this study was to analyze the cytokine and chemokine reaction in both lungs, pleural space and blood in patients undergoing lung resection with OLV with special interest in the chemokine growth-regulated peptide alpha (GROalpha) which is the human equivalent to the rat cytokine-induced neutrophil chemoattractant-1 (CINC-1). METHODS: Broncho-alveolar lavage (BAL) fluid of both the collapsed, operated and the ventilated, non-operated lung, respectively, pleural space drainage fluid and blood was collected and the concentrations of interleukin (IL)-6, IL-1RA and GROalpha were determined with enzyme-linked immunosorbent assays in 15 patients. RESULTS: Substantial inter-individual differences in the BAL fluid between patients in cytokine and chemokine levels occurred. In the pleural fluid and the blood these inter-individual differences were less pronounced. Both sides of the lung were affected and showed a significant increase in IL-6 and IL-1RA concentrations over time but not in GROalpha concentrations. Except for IL-6, which increased more in the collapsed, operated lung, no difference between the collapsed, operated and the ventilated, non-operated lung occurred. In the blood, IL-6 and IL-1RA increased early, already at the end of surgery. GROalpha was not detectable. In the pleural fluid, both cytokine and chemokine concentrations increased by day one. The increase was significantly higher in the pleural fluid compared to the blood. CONCLUSION: The inflammatory response of cytokines affects both the collapsed, operated and the ventilated, non-operated lungs. The difference in extent of response underlines the complexity of the inflammatory processes during OLV. In contrast to the cytokines, the chemokine GROalpha concentrations did not react in the BAL fluid or in the blood. This indicates that GROalpha might not be useful as marker for the inflammatory reaction in complex surgical procedures. PMID- 22078634 TI - Interleukin-13 enhanced Ca2+ oscillations in airway smooth muscle cells. AB - Physiological mechanisms associated with interleukin-13 (IL-13), a key cytokine in asthma, in intracellular Ca(2+) signaling in airway smooth muscle cells (ASMCs) remain unclear. The aim of this study was to assess effects of IL-13 on Ca(2+) oscillations in response to leukotriene D4 (LTD4) in human cultured ASMCs. LTD4-induced Ca(2+) oscillations in ASMCs pretreated with IL-13 were imaged by confocal microscopy. mRNA expressions of cysteinyl leukotriene 1 receptors (CysLT1R), CD38, involved with the ryanodine receptors (RyR) system, and transient receptor potential canonical (TRPC), involved with store-operated Ca(2+) entry (SOCE), were determined by real-time PCR. In IL-13-pretreated ASMCs, frequency of LTD4-induced Ca(2+) oscillations and number of oscillating cells were significantly increased compared with untreated ASMCs. Both xestospongin C, a specific inhibitor of inositol 1,4,5-triphosphate receptors (IP(3)R), and ryanodine or ruthenium red, inhibitors of RyR, partially blocked LTD4-induced Ca(2+) oscillations. Ca(2+) oscillations were almost completely inhibited by 50 MUM of 2-aminoethoxydiphenyl borate (2-APB), which dominantly blocks SOCE but not IP(3)R at this concentration. Pretreatment with IL-13 increased the mRNA expressions of CysLT1R and CD38, but not of TRPC1 and TRPC3. We conclude that IL 13 enhances frequency of LTD4-induced Ca(2+) oscillations in human ASMCs, which may be cooperatively modulated by IP(3)R, RyR systems and possibly by SOCE. PMID- 22078635 TI - IL-4 acts as a potent stimulator of IFN-gamma expression in CD8+ T cells through STAT6-dependent and independent induction of Eomesodermin and T-bet. AB - CD8+ T cell synthesis of IFN-gamma is an important component of the CD8+ T cell immune response. In short-term cultures of murine pan-T cells, we found that IL-4 was the principal cytokine responsible for driving IFN-gamma synthesis by CD3/CD28-activated CD8+ T cells. IL-4 was able to induce low levels of IFN-gamma mRNA in CD8+ T cells even in the absence of CD3/CD28 engagement, although concomitant CD3/CD28 stimulation was necessary for IFN-gamma secretion. IL-4 induction of IFN-gamma was explained by its ability to induce Eomesodermin and T bet transcription factors whose expression was further increased by CD3/CD28. Expression of Eomesodermin, T-bet and IFN-gamma induced by IL-4 was partially dependent upon activation of MAPK and PI3K but independent of the canonical IL-4 activated transcription factor, STAT6. In contrast, expression of IFN-gamma induced by IL-4/CD3/CD28 stimulation showed additional dependency upon STAT6 which functions to increase expression of Eomesodermin specifically. These novel findings point to a function for IL-4 as a direct regulator of IFN-gamma expression in CD8+ T cells and reveal the molecular mechanisms involved. PMID- 22078636 TI - Urine IgM-excretion as a prognostic marker for progression of type 2 diabetic nephropathy. AB - Although the clinical manifestations of type 2 diabetic nephropathy and decline in kidney function are similar to those in type 1, the clinical course and the renal structural changes are more heterogeneous in type 2 diabetic patients. Previous studies have shown that an increased urine IgM excretion in patients with type 1 diabetic nephropathy was associated with poor outcome. In the present follow-up study we examine the prognostic value of baseline urine IgM excretion in patients with type 2 diabetes mellitus. METHODS: A cohort of 106 (74 male and 32 female) patients with type 2 diabetes regularly attending our diabetes out patient clinic at Skane University Hospital in Lund. They were recruited prospectively under the period between 1992 and 2004. Patients were followed-up until January 2009. The end point was cardiovascular (CV) death or end-stage renal disease (ESRD). The median follow-up time was 5 years (0.5-13 years). Participants were divided according to degree of albuminuria and IgM-uria. RESULTS: During follow-up time, 28 (19 male and 9 female) patients died of CV events and 41 (26 male and 15 female) developed ESRD. The risk of CV mortality was 2.4 fold, and the risk of renal failure 4.9 fold higher in patients with increased urine IgM excretion compared to patients with low urine IgM excretion. Stratified analysis showed that an increased urine IgM excretion was an independent predictor of renal and cardiovascular death irrespective of the degree of albuminuria (HR=3.6, 95% CI: 2.1-6.0, P<0.001). In conclusion, type 2 diabetic nephropathy patients with high urine IgM excretion rates carry an increased risk of renal and cardiovascular death. PMID- 22078637 TI - Health problems and disability in long-term sickness absence: ICF coding of medical certificates. AB - BACKGROUND: The purpose of this study was to test the feasibility of International Classification of Functioning, Disability and Health (ICF) and to explore the distribution, including gender differences, of health problems and disabilities as reflected in long-term sickness absence certificates. METHODS: A total of 433 patients with long sick-listing periods, 267 women and 166 men, were included in the study. All certificates exceeding 28 days of sick-listing sent to the local office of the Swedish Social Insurance Administration of a municipality in the Stockholm area were collected during four weeks in 2004-2005. ICD-10 medical diagnosis codes in the certificates were retrieved and free text information on disabilities in body function, body structure or activity and participation were coded according to ICF short version. RESULTS: In 89.8% of the certificates there were descriptions of disabilities that readily could be classified according to ICF. In a reliability test 123/131 (94%) items of randomly chosen free text information were identically classified by two of the authors. On average 2.4 disability categories (range 0-9) were found per patient; the most frequent were 'Sensation of pain' (35.1% of the patients), 'Emotional functions' (34.1%), 'Energy and drive functions' (22.4%), and 'Sleep functions' (16.9%). The dominating ICD-10 diagnostic groups were 'Mental and behavioural disorders' (34.4%) and 'Diseases of the musculoskeletal system and connective tissue' (32.8%). 'Reaction to severe stress and adjustment disorders' (14.7%), and 'Depressive episode' (11.5%) were the most frequent diagnostic codes. Disabilities in mental functions and activity/participation were more commonly described among women, while disabilities related to the musculoskeletal system were more frequent among men. CONCLUSIONS: Both ICD-10 diagnoses and ICF categories were dominated by mental and musculoskeletal health problems, but there seems to be gender differences, and ICF classification as a complement to ICD-10 could provide a better understanding of the consequences of diseases and how individual patients can cope with their health problems. ICF is feasible for secondary classifying of free text descriptions of disabilities stated in sick leave certificates and seems to be useful as a complement to ICD-10 for sick listing management and research. PMID- 22078638 TI - Adherence to breast and cervical cancer screening in Spanish women with diabetes: associated factors and trend between 2006 and 2010. AB - AIM: This study aimed to assess the adherence to breast and cervical cancer screening of women with diabetes mellitus (DM), and the associated factors and trend of use over time of these preventative services between 2006 and 2010 in Spain. METHODS: The study used data from a population of women aged greater or equal to 18 years (n=11,957) who participated in the European Health Interview Survey in Spain (EHISS, 2009). Diabetes status was self-reported and included those with type 2 DM. Adherence to screening for cancer prevention was assessed by asking women aged greater or equel to 40 years whether they had undergone mammography and a Papanicolaou (Pap) cervical smear (in those aged 18-69 years) within the previous 2 and 3 years, respectively. Independent variables included sociodemographic and health-related characteristics. Also, the age-standardized prevalences of mammography and Pap smear uptake were compared in women with diabetes between 2006 and 2010. RESULTS: Among the diabetic women, 37.9% underwent mammography and 49.1% had a Pap smear vs 53.8% and 64%, respectively, in women without diabetes, with corresponding adjusted odds ratios of 0.81 (95% CI: 0.68-0.97) and 0.74 (95% CI: 0.60-0.91). Among diabetic women, attending more "physician visits" was a positive predictor of having both screening tests. Also, a higher monthly income level was associated with mammography uptake, and a higher educational level with Pap smear uptake. There was also a significant decrease in mammography screening uptake between 2006 and 2010 compared with a stable rate of uptake of cervical cancer screening. CONCLUSION: Spanish women with diabetes consistently underuse breast and cervical cancer screening tests compared with non-diabetic women. The decline in mammography uptake rates needs to be carefully monitored and may even call for intervention. PMID- 22078639 TI - The question shapes the answer: the neural correlates of task differences reveal dynamic semantic processing. AB - Task effects in semantic processing were investigated by contrasting the neural activation associated with two semantic categorization tasks (SCT) using event related fMRI. The two SCTs involved different decision categories: is it an animal? vs. is it a concrete thing? Participants completed both tasks and, across participants, the same core set of items were presented in both tasks. Results showed task differences in the neural activation associated with these items: in the animal SCT there was greater activation in a number of frontal and temporal regions, including left superior and middle temporal gyri, while in the concrete SCT there was greater activation in left medial frontal gyrus and bilaterally in the precentral gyri. These results are interpreted as evidence of top-down modulation of semantic processing; participants make adjustments to optimize performance in a given task and these adjustments have consequences for the activation observed. PMID- 22078640 TI - From TAVI to TAVR: transforming imagination into reality. PMID- 22078641 TI - Absence of circadian variation of acute coronary syndrome onset in chronic kidney disease patients. AB - BACKGROUND: Several studies have reported on the circadian variation in acute coronary syndrome (ACS) onset. The influence of morning blood pressure surge, platelet aggregation and sympathetic activity is believed to cause this circadian variation. At the same time, a high frequency of ACS and sympathetic nerve hyperactivity has been reported in chronic kidney disease (CKD). Therefore, we investigated the relationship between CKD and the circadian variation in ACS. METHODS: This study included 460 consecutive patients undergoing primary percutaneous coronary intervention for ACS between 2003 and 2009. Patients undergoing hemodialysis were excluded. The subjects were divided into two groups according to the value of estimated glomerular filtration rate (eGFR): CKD group [eGFR <= 60 ml/min/1.73 m2 by Modification of Diet in Renal Disease (MDRD) equation] and No CKD group (eGFR > 60 ml/min/1.73 m2 by MDRD equation). Clinical and angiographic characteristics, as well as the time distribution of ACS, were compared between the two groups. RESULTS: There were no significant differences in clinical and angiographic characteristics between the two groups. A significant increase in morning coronary events was observed in the No CKD group. This increase was absent in the CKD group. CONCLUSIONS: The existence of CKD affected the circadian variation associated with the more frequent ACS onset observed in the No CKD group patients. Probably, these data may suggest the cause of frequent cardiovascular events in CKD patients. PMID- 22078642 TI - Improving patient outcomes in glioblastoma through integration of recent data: introduction. PMID- 22078643 TI - The impact of recent data on the optimization of standards of care in newly diagnosed glioblastoma. AB - Glioblastoma is an aggressive form of brain cancer with a poor long-term prognosis. Treatment regimens for newly diagnosed disease range from surgical resection alone to surgery followed by radiotherapy with concurrent and adjuvant chemotherapy. Ongoing investigations are focused on optimization of chemotherapy by improving dosing and duration schedules and utilization of biomarkers for patient selection. Our understanding of glioblastoma tumor biology, the role of molecular signaling pathways, cellular repair mechanisms, and angiogenesis has increased greatly over the past few years, leading to the investigation of a variety of targeted therapies. In addition, advances in radiographic assessment have significantly impacted not only improvement in diagnosis, but interpretation of response to therapy. In order to effectively evaluate the clinical utility of new agents, as well as incorporate advances in radiographic assessment, changes to current clinical trial design need to be considered. This article reviews the care for newly diagnosed glioblastoma, as well as how recent findings might be incorporated into patient care. PMID- 22078644 TI - Understanding glioblastoma tumor biology: the potential to improve current diagnosis and treatments. AB - Glioblastoma (GBM) is a highly malignant brain cancer characterized by uncontrolled cellular proliferation, diffuse infiltration, a tendency for necrosis, significant angiogenesis, intense resistance to apoptosis, and widespread genomic aberrations. Prognosis is poor and treatments are largely palliative, although there are subsets of patients that have prolonged survival. Greater understanding of the tumor biology of GBM has been achieved in the past decade, leading to the prospect of novel targeted therapies and biomarker-based individualization of therapy. The goal of this review is to describe the tumor biology and pathologic features of GBM, guidelines for classification and diagnosis, the current status of prognostic and predictive biomarkers, and the role of the blood-brain barrier in delivering therapy for GBM. PMID- 22078645 TI - Recurrent glioblastoma: a fresh look at current therapies and emerging novel approaches. AB - Despite international efforts, the treatment of recurrent glioblastoma (GBM) remains challenging. Although advances in surgical resection, the use of radiotherapy, and, predominantly, improved medical therapies have led to incremental improvements in median survival, few options exist for the management of recurrent or resistant disease. Insight into the molecular pathogenesis of GBM has led to the recent development of targeted therapeutic strategies aimed at the interruption of key molecular signaling pathways. However, due to the complex and redundant activation of the signaling mechanisms in GBM tumors, the evaluation of targeted agents in clinical trials has been largely limited. The ongoing effort to identify effective strategies for the treatment of recurrent GBM includes combination strategies with agents that target complementary or redundant pathways. Incorporation of novel trial designs that permit simultaneous evaluation of several agent combinations and allow for rapid discontinuation of ineffective regimens can accelerate the clinical evaluation of such candidate regimens. This review discusses strategies and outcomes of existing and emerging treatment approaches, and the challenges associated with the integration of novel therapies into clinical practice. PMID- 22078646 TI - Altered inhibition of negative emotions in subjects at family risk of major depressive disorder. AB - Unaffected 1st degree relatives of patients with major depressive disorder (MDD) are more likely to develop MDD than healthy controls. The aim of our study was to establish neuronal correlates of familial susceptibility in the process of inhibition of emotional information. Unaffected 1st degree relatives of patients with MDD (N = 21) and matched healthy controls (N = 25) underwent a functional magnetic resonance imaging procedure with an inhibition task. Blood oxygenated level dependent signal was evaluated for the two groups during inhibition of positive, negative and neutral information. In a 2 * 3 ANOVA unaffected relatives of patients with MDD were compared to healthy controls, jointly and separately for all three levels of emotional valence of the information. The interaction between group and emotional valence of the inhibited information was significant, indicating "a negative neural drift" in unaffected relatives of patients with MDD. The unaffected relatives of patients with MDD displayed an increased activation during inhibiting of negative material in the right middle cingulate cortex and the left caudate nucleus (p < 0.05, family wise error corrected). There was no difference between the two groups in terms of inhibiting positive or neutral stimuli. Our findings provide the first evidence that unaffected relatives of patients with MDD differ from the standard population in terms of neural correlates of inhibition of negative emotional information. Overactivation of cingulate cortex and caudate nucleus may indicate a learnt strategy aimed at coping with increased susceptibility to negative information schemata and may have future consequences for therapy. PMID- 22078647 TI - Usefulness of procalcitonin and C-reactive protein in the acute meningitis in the emergency department. PMID- 22078648 TI - Spanish consensus on the use of natalizumab (Tysabri((r)))--2011. AB - INTRODUCTION: Natalizumab is very effective at reducing relapses and delaying disease progression in patients with relapsing-remitting multiple sclerosis (RRMS). However, treatment has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The aim of this article is to provide a consensus view on the assessment and stratification of these risks, and to improve the management of natalizumab-treated patients. DEVELOPMENT: At an initial meeting of experts on multiple sclerosis (the authors of this consensus), the relevant topics of the consensus were determined and assigned for further elaboration. Topics included how to establish benefit and risk in general, stratification for risk of PML, informing patients of benefits/risks, and how to monitor patients during treatment and after discontinuing treatment. During the drafting phase, all available information published or presented at international meetings was reviewed. After a series of review sessions and meetings, the final draft was produced. CONCLUSIONS: Although natalizumab is a very effective drug, its use needs to be considered carefully in view of possible adverse effects and the risk of PML in particular. The neurologist should carefully explain the risks and benefits of treatment in terms the patient can best understand. Before starting treatment, baseline laboratory tests and magnetic resonance imaging (MRI) should be available for future comparisons in the event of suspected PML. The risk of PML should be stratified into high, medium and low risk groups according to presence or absence of anti-JC virus antibodies, prior immunosuppressive therapy, and treatment duration. The follow-up, and frequency of MRI scans in particular, should depend on the risk group to which patient belongs. As our understanding of the risk factors for PML develops, it should be possible to offer patients increasingly individualised therapy. This is a consensus that establishes general recommendations, but neurologists must use their clinical expertise to monitor patients individually. PMID- 22078649 TI - [Whipple's disease: multiple systemic and neurological relapses. Reply]. PMID- 22078650 TI - Unilateral eyelid myokymia as a form of presentation of multiple sclerosis. PMID- 22078651 TI - Drug-resistant epilepsy: current recommendations for diagnosis and treatment in Spain. AB - INTRODUCTION: Drug-resistant epilepsy (DRE) is a top-priority social health problem which requires early individual treatment due to its dramatic repercussions for the patient and society. DEVELOPMENT: The International League Against Epilepsy (ILAE) has recently defined DRE as that in which the seizures are not controlled after having correctly taken two appropriate and well tolerated anti-epileptic drugs, with lack of control being understood as the appearance of seizures within one year or in a period less than three times the inter-seizure interval before starting treatment. This International Society recommends a rapid and detailed assessment of all patients in an Epilepsy Unit. A Clinical Epilepsy Unit (CEU) is understood as a group of professionals who, acting in collaboration, have the diagnosis and treatment of the patient with epilepsy as their primary objective. CEUs in Spain may be stratified into different levels depending on the activity carried out in each of them. The specific epilepsy clinic is considered the fundamental type of CEU and includes the necessary figure of an expert in epilepsy. Prolonged video-monitoring is performed in medical CEUs. In medical-surgical CEUs epilepsy surgery with varying degrees of difficulty is also performed. CONCLUSIONS: All CEUs must cooperate with consensus protocols, and there must be a two-way flow between them. Stratification of CEUs increases efficacy and efficiency, due to there being a sufficient number of them to ensure easy access by all patients with epilepsy. PMID- 22078653 TI - A patient with convulsive syndrome and partial tetrasomy of chromosome 15. PMID- 22078652 TI - Consensus-recommended diagnostic and therapeutic guidelines for drug-resistant epilepsy in Spain (Consenso RATE-Espana). AB - OBJECTIVE: To ascertain the opinions of an Epilepsy Expert Group and prepare a consensus document on the definition of drug-resistant epilepsy (DRE) according to the International League Against Epilepsy (ILAE) and the different healthcare levels for the patient with epilepsy in Spain. MATERIAL AND METHODS: The study was conducted using the Delphi method, by means of successive rounds of questionnaires. A scientific committee prepared a preliminary document and fourteen associated questions, which were sent by e-mail to the panel of experts. They included items related to the concept of DRE, health care levels and the route between these levels for patients with DRE. RESULTS: A total of 41 experts answered the questionnaire. They agreed regarding the necessity and applicability of the DRE definition according to the ILAE, the need for an expert panel on epilepsy, specialist epilepsy clinics, and clinical epilepsy units stratified depending on the level of activities they carried out. There was moderate consensus on the resources and activity of the clinical units of reference and there was no consensus on the referral of patients who have suffered an epileptic seizure to an epilepsy clinic. CONCLUSIONS: The expert panel agreed with the definition of DRE according to the ILAE and on referring patients with DRE for a detailed study in an epilepsy clinic or epilepsy clinical unit. They highlighted the need for video-EEG monitoring in the study of patients with DRE and the need to propose other forms of treatment in selected patients. PMID- 22078654 TI - Acute persistent dysarthria and dizziness with previous neurological study: is it enough to establish a diagnosis? PMID- 22078656 TI - Altered patterns of toll-like receptor gene expression in cull cows infected with Mycobacterium avium subsp. paratuberculosis. AB - Johne's disease caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic enteric disease of cattle. The mechanism how MAP can co-exist in the gastro-intestinal tract despite a massive infiltration of immune cells is not known. Toll-like receptors (TLRs) are known to play an important role in both innate and acquired immune responses but it is unclear what role different TLRs play in response to MAP. In this study, 38 cull cows from herds infected with MAP were classified into four groups, based on MAP culture from gut tissues and histopathological lesion scores. The expression of TLR1, 2 and 4 mRNA from MAP antigen-stimulated mesenteric lymph node (MLN) cultures and peripheral blood mononuclear cells (PBMCs) and in the MLN and ileum tissues of these animals was determined. MAP antigen-specific expression of TLR1 in MLN and PBMC was significantly lower in the MAP-infected groups than the non-infected control group, suggesting that in MAP-infected animals there is impairment in the up regulation of TLR1 in response to MAP antigen. TLR4 expression in MLN tissues was significantly higher in the severely infected group than the control group suggesting up-regulation of endogenous TLR4 expression at a site of MAP infection in animals severely affected with Johne's disease. A preliminary screening of TLR1, 2 and 4 in the cull cows revealed the presence of polymorphisms in TLR1 and TLR2. In summary, one mechanism how MAP may subvert the immune system is that there is an apparent lack of recognition of MAP antigens as foreign by TLR1 in MAP-infected cows. PMID- 22078655 TI - The feasibility of age-specific travel restrictions during influenza pandemics. AB - BACKGROUND: Epidemiological studies have shown that imposing travel restrictions to prevent or delay an influenza pandemic may not be feasible. To delay an epidemic substantially, an extremely high proportion of trips (~99%) would have to be restricted in a homogeneously mixing population. Influenza is, however, strongly influenced by age-dependent transmission dynamics, and the effectiveness of age-specific travel restrictions, such as the selective restriction of travel by children, has yet to be examined. METHODS: A simple stochastic model was developed to describe the importation of infectious cases into a population and to model local chains of transmission seeded by imported cases. The probability of a local epidemic, and the time period until a major epidemic takes off, were used as outcome measures, and travel restriction policies in which children or adults were preferentially restricted were compared to age-blind restriction policies using an age-dependent next generation matrix parameterized for influenza H1N1-2009. RESULTS: Restricting children from travelling would yield greater reductions to the short-term risk of the epidemic being established locally than other policy options considered, and potentially could delay an epidemic for a few weeks. However, given a scenario with a total of 500 imported cases over a period of a few months, a substantial reduction in the probability of an epidemic in this time period is possible only if the transmission potential were low and assortativity (i.e. the proportion of contacts within-group) were unrealistically high. In all other scenarios considered, age-structured travel restrictions would not prevent an epidemic and would not delay the epidemic for longer than a few weeks. CONCLUSIONS: Selectively restricting children from traveling overseas during a pandemic may potentially delay its arrival for a few weeks, depending on the characteristics of the pandemic strain, but could have less of an impact on the economy compared to restricting adult travelers. However, as long as adults have at least a moderate potential to trigger an epidemic, selectively restricting the higher risk group (children) may not be a practical option to delay the arrival of an epidemic substantially. PMID- 22078657 TI - A model of delivering multi-disciplinary care to people with 46 XY DSD. AB - In 2006, a consensus statement was jointly produced by the Lawson Wilkins Pediatric Endocrine Society (LWPES) and the European Society of Paediatric Endocrinology (ESPE) concerning the management of disorders of sex development (DSD) [1]. A recommendation provided by this consensus was that evaluation and long-term care for people affected by DSD should be performed at medical centers with multi-disciplinary teams experienced in such conditions. Here we provide our team's interpretation of the 2006 consensus statement recommendations and its translation into a clinical protocol for individuals affected by 46 XY DSD with either female, or ambiguous, genitalia at birth. Options for medical and surgical management, transitioning of care, and the use of mental health services and peer support groups are discussed. Finally, we provide preliminary data to support the application of our model for delivering multi-disciplinary care and support to patients and their families. PMID- 22078659 TI - Model of care for women at increased risk of breast and ovarian cancer. PMID- 22078658 TI - Iodine deficiency influences thyroid autoimmunity in old age--a comparative population-based study. AB - OBJECTIVE: To assess thyroid autoimmunity among elderly people living in an area with low iodine intake compared to the sustained recommended iodine intake from a natural source, and to estimate the importance of migration. DESIGN AND SETTING: Iodine content of drinking water is highly different in the Danish towns Randers and Skagen. We collected blood and spot urine samples from 430 long-term Randers and Skagen dwellers aged 75-80 years, who filled in a questionnaire. We measured thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in serum and iodine and creatinine in urine. RESULTS: Participation rate was 47% (n=212 (men/women 82/130) in Randers; 218 (84/134) in Skagen). Iodine deficiency prevailed in Randers while Skagen dwellers were iodine replete (median urinary iodine 74 MUg/24h vs. 184 MUg/24h, p<0.001). Thyroid antibodies were more frequent in Randers than in Skagen residents (42% vs. 32%; p=0.006) and more likely with iodine excretion <50 MUg/24h (OR, 95%CI: 1.9, 1.1-3.4). Differences between towns increased with longer duration of residence as trends in the occurrence of TGAb and TPOAb were opposite (p<0.001; p=0.007). CONCLUSIONS: Thyroid autoantibodies were common in old age, influenced by the iodine intake level, and the lowest frequency was found at the recommended iodine intake level. PMID- 22078660 TI - Efficacy and tolerability of calcium, vitamin D and a plant-based omega-3 oil for osteopenia: a pilot RCT. AB - OBJECTIVES: Our pilot study tested the efficacy, acceptability and tolerability of DHA supplementation in addition to calcium and vitamin D in individuals with osteopenia. STUDY DESIGN: 40 participants were randomised to either algal oil containing 400mg docosahexanoic acid (DHA) daily or placebo. All participants received 1200 mg calcium carbonate with vitamin D(3) 1000 IU daily. MAIN OUTCOME MEASURES: Bone mineral density (BMD) was measured at baseline and 12 months. Bone turnover was assessed with serum c-terminal telopeptides (CTx) at baseline and 12 months. Tolerability and acceptability were assessed using a validated questionnaire. RESULTS: Mean CTx was suppressed after 12 months for all participants (p=0.04) with no difference in effect size between DHA and control groups (p=0.53). Changes in CTx at 12 months were significantly correlated with changes in BMD at the lumbar spine (p=0.01) and total proximal femur (TPF) (p=0.03). There was a non-significant trend towards rising BMD at 12 months. Participants rated the supplements as tolerable and acceptable, with few adverse events. CONCLUSIONS: The combination of oral calcium, vitamin D(3) and DHA was safe, tolerable and acceptable when used for 12 months by osteopenic individuals in this pilot study. The combination had a positive effect on bone health as indicated by serum CTx, with no effect demonstrated from the addition of DHA 400mg. Changes in BMD at the lumbar spine and TPF were significantly correlated with changes in CTx, which may be useful in monitoring bone health and response to treatment. PMID- 22078661 TI - Spinal cord stimulation of dorsal columns in a rat model of neuropathic pain: evidence for a segmental spinal mechanism of pain relief. AB - Although spinal cord stimulation (SCS) of the dorsal columns is an established method for treating chronic neuropathic pain, patients still suffer from a substantial level of pain. From a clinical perspective it is known that the location of the SCS is of pivotal importance, thereby suggesting a segmental spinal mode of action. However, experimental studies suggest that SCS acts also through the modulation of supraspinal mechanisms, which might suggest that the location is unimportant. Here we investigated the effect of the rostrocaudal location of SCS stimulation and the effectiveness of pain relief in a rat model of chronic neuropathic pain. Adult male rats (n=45) were submitted to a partial ligation of the sciatic nerve. The majority of animals developed tactile hypersensitivity in the nerve lesioned paw. All allodynic rats were submitted to SCS (n=33) for 30 minutes (f=50 Hz; pulse width 0.2 ms). In one group (n=16) the electrodes were located at the level where the injured sciatic nerve afferents enter the spinal cord (T13), and in a second group (n=17) the electrodes were positioned at more rostral levels (T11) as verified by X-ray. A repositioning experiment of electrodes from T12 to T13 was performed in 2 animals. Our data demonstrate that SCS of the dorsal columns at the level where the injured fibers enter the spinal cord dorsal horn result in a much better pain-relieving effect than SCS at more rostral levels. From this we conclude that SCS in treatment of neuropathic pain acts through a segmental spinal site of action. PMID- 22078662 TI - [Marketing-based prescribing]. PMID- 22078663 TI - A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery. AB - INTRODUCTION: With the recent publication of new criteria for the diagnosis of preclinical Alzheimer's disease (AD), there is a need for neuropsychological tools that take premorbid functioning into account in order to detect subtle cognitive decline. Using demographic adjustments is one method for increasing the sensitivity of commonly used measures. We sought to provide a useful online z score calculator that yields estimates of percentile ranges and adjusts individual performance based on sex, age and/or education for each of the neuropsychological tests of the National Alzheimer's Coordinating Center Uniform Data Set (NACC, UDS). In addition, we aimed to provide an easily accessible method of creating norms for other clinical researchers for their own, unique data sets. METHODS: Data from 3,268 clinically cognitively-normal older UDS subjects from a cohort reported by Weintraub and colleagues (2009) were included. For all neuropsychological tests, z-scores were estimated by subtracting the raw score from the predicted mean and then dividing this difference score by the root mean squared error term (RMSE) for a given linear regression model. RESULTS: For each neuropsychological test, an estimated z-score was calculated for any raw score based on five different models that adjust for the demographic predictors of SEX, AGE and EDUCATION, either concurrently, individually or without covariates. The interactive online calculator allows the entry of a raw score and provides five corresponding estimated z-scores based on predictions from each corresponding linear regression model. The calculator produces percentile ranks and graphical output. CONCLUSIONS: An interactive, regression-based, normative score online calculator was created to serve as an additional resource for UDS clinical researchers, especially in guiding interpretation of individual performances that appear to fall in borderline realms and may be of particular utility for operationalizing subtle cognitive impairment present according to the newly proposed criteria for Stage 3 preclinical Alzheimer's disease. PMID- 22078664 TI - Mollicutes contamination: a new strategy for an effective rescue of cancer cell lines. AB - Mollicutes contaminations of cellular models can have marked effects on gene expression and cell behaviour in vitro leading to the production of unreliable data, unsafe biopharmaceutical drugs or to the loss of cell culture itself. Fortunately, irreplaceable cell culture can be cured by decontamination with the specific antibiotic regimen. Here, we describe the treatment of 35 mycoplasma positive cell lines by the use of the novel antibiotic Mycozap((r)) as well as evaluate its eradication performance versus the well-known routinely employed BM Cyclins and fluoroquinolones molecules (175 treatments). Our data evidenced: i) the permanent elimination of mycoplasma infection by MycoZap((r)), MRA, Enrofloxacin, Ciprofloxacin and BM-Cyclins in 46%, 29%, 40%, 43%, and 57% of the cultures, respectively; ii) a significant correlation between MRA and Ciprofloxacin eradication profile, as determined by the Spearman correlation coefficient (r = 0.3469, p < 0.05); iii) a mycoplasma eradication in 100% of cell lines by the exclusive adoption of MycoZap((r)), Ciprofloxacin, Enrofloxacin, BM Cyclin 1-2 antibiotic regimen, with the MRA exclusion; iv) the MycoZap((r)) effectiveness even in case of a mycoplasmal load higher than 50 CFU/mL, as for SH SY5Y and Neuro2A cells. In conclusion, we want to suggest an optimized antibiotic panel to get 100% mycoplasma-clearance especially in case of unique or treatment resistant cellular models. PMID- 22078665 TI - Evaluation of the equity of age-sex adjusted primary care capitation payments in Ontario, Canada. AB - OBJECTIVE: Several innovative primary care models have recently been introduced in Ontario, Canada. Two of these models are funded primarily through age-sex based capitation. There is concern that adjusting capitation rates for age and sex alone does not take into account the increased morbidity burden and health care needs that are associated with lower socioeconomic status. This study assesses the extent to which the current age-sex capitation rates in Ontario reflect health care needs of patients across socioeconomic status by comparing Ontario's age-sex adjusted capitation remuneration rate index with relative expected health care resource use by socioeconomic status (SES). METHODS: This study used administrative data collected by the Ontario Ministry of Health and Long-Term Care. The study sample was those patients who were enrolled to a FHN continuously from September 1, 2005 to August 31, 2006. Standardized expected health care utilization was calculated based on morbidity burden using The Johns Hopkins Adjusted Clinical Groups (ACG) Case-mix System and compared with standardized capitation rates across and within neighbourhood income quintiles. RESULTS: Among those in the lowest income group expected utilization was much higher than the age-sex capitation rates, while the opposite was true for those in the highest income group. CONCLUSIONS: The findings suggests that under the physician reimbursement system used in Family Health Networks in Ontario, physicians are under-compensated for the health care needs of low income patients and over-compensated for the needs of high income patients. Adjusting capitation rates for morbidity burden in addition to age and sex may reduce incentives to preferentially enrol patients with higher socioeconomic status. PMID- 22078666 TI - Lipoprotein(a) and inflammation in patients with atrial fibrillation after electrical cardioversion. AB - BACKGROUND: Recently few studies tried to confirm the association between AF and lipoprotein(a) (Lp(a)), however the results remained conflicted. In present study we evaluated the possible interaction between Lp(a), inflammatory state and echocardiographic characteristics in patients after successful electrical cardioversion (EC) of persistent AF. We also tried to investigate the role of Lp(a) as a possible prognostic factor for AF recurrence after successful EC. RESULTS: Data of 79 patients admitted due to planned EC was analyzed. After successful procedure patients were monitored for 2 years. For analytical purposes patients were divided in two groups according to AF recurrence. There was no significant difference between Lp(a) levels in both groups. We also didn't find any positive correlation between Lp(a) and CRP levels, as well as between Lp(a) levels and left atrium diameter. For logistic and survival analysis optimal cut off value of Lp(a)>=0.32 (upper quartile) was used. In logistic regression model with AF recurrence as dependent variable Lp(a) didn't show any statistically significant association with AF recurrence. Survival analysis showed slightly higher AF recurrence rate in group with higher Lp(a) levels but not to the level of statistical significance (log rank test, p=0.62). CONCLUSIONS: We weren't able to confirm the association between Lp(a) levels and AF recurrence, inflammation and left atrium diameter in patients after successful EC of persistent AF. Further studies are needed to elucidate the role of Lp(a) in this clinical setting. PMID- 22078667 TI - Identifying socio-demographic and socioeconomic determinants of health inequalities in a diverse London community: the South East London Community Health (SELCoH) study. AB - BACKGROUND: Responses to public health need require information on the distribution of mental and physical ill health by demographic and socioeconomic factors at the local community level. METHODS: The South East London Community Health (SELCoH) study is a community psychiatric and physical morbidity survey. Trained interviewers conducted face-to-face computer assisted interviews with 1698 adults aged 16 years and over, from 1076 randomly selected private households in two south London boroughs. We compared the prevalence of common mental disorders, hazardous alcohol use, long standing illness and general physical health by demographic and socioeconomic indicators. Unadjusted and models adjusted for demographic and socioeconomic indicators are presented for all logistic regression models. RESULTS: Of those in the sample, 24.2% reported common mental disorder and 44.9% reported having a long standing illness, with 15.7% reporting hazardous alcohol consumption and 19.2% rating their health as fair or poor. The pattern of indicators identifying health inequalities for common mental disorder, poor general health and having a long term illness is similar; individuals who are socioeconomically disadvantaged have poorer health and physical health worsens as age increases for all groups. The prevalence of poor health outcomes by ethnic group suggests that there are important differences between groups, particularly for common mental disorder and poor general health. Higher socioeconomic status was protective for common mental disorder, fair or poor health and long standing illness, but those with higher socioeconomic status reported higher levels of hazardous alcohol use. The proportion of participants who met the criteria for common mental disorder with co-occurring functional limitations was similar or greater to those with poor physical health. CONCLUSIONS: Health service providers and policy makers should prioritise high risk, socially defined groups in combating inequalities in individual and co-occurring poor mental and physical problems. In population terms, poor mental health has a similar or greater burden on functional impairment than long term conditions and perceived health. PMID- 22078668 TI - When parents' affection depends on child's achievement: parental conditional positive regard, self-aggrandizement, shame and coping in adolescents. AB - We examined the idea that adolescents' perceptions of their mothers as using parental conditional positive regard (PCPR) to promote academic achievement are associated with maladaptive self feelings and coping. A study of 153 adolescents supported the hypothesis that PCPR predicts self-aggrandizement following success and self devaluation and shame following failure, which then predict compulsive over-investment. PCPR functioned as a unique predictor of maladaptive self feelings and coping also when the effects of perceived parental conditional negative regard or psychological control were controlled for. The findings suggest that the experience of one's mother as using conditional positive regard to promote achievement leads to a non-optimal self-esteem dynamics, in which people vacillate between feelings of grandiosity following success and self derogation and shame following failure, which in turn promote a rigid and stressful mode of coping. Thus, the practice of PCPR, although seemingly benign, appears to carry significant emotional and coping costs for adolescents. PMID- 22078669 TI - Documenting different domains of promotion of autonomy in families. AB - Parental promotion of autonomy for offspring well-being has been widely recognized in developmental psychology. Recent studies, however, show that this association varies across cultures. Such variation may reflect inappropriate measurement of this dimension of parenting. Therefore, three existing measures of promotion of autonomy were used to derive different dimensions related to the promotion of autonomy in three different domains - promotion of autonomous thought, promotion of autonomous decision-making, and promotion of physical separation. The cross-cultural significance of this three-component model was tested in samples of late adolescents (n = 1361) from four nations- the US, Belgium, Italy and China. Data from all four countries best fit a three dimensional model but the covariance between the three dimensions was moderated by culture. Culture also moderated the impact of promotion of autonomy on offspring well-being. PMID- 22078670 TI - Non-medical use of painkillers in the USA. PMID- 22078671 TI - Improving rates of surgery for lung cancer. PMID- 22078672 TI - Moving toward precision medicine. PMID- 22078673 TI - Targeting of household air pollution: interpretation of RESPIRE. PMID- 22078674 TI - Reporting quality of life in clinical trials: a CONSORT extension. PMID- 22078676 TI - William Seeley: brain explorer. PMID- 22078678 TI - Outpatient treatment for pulmonary embolism. PMID- 22078679 TI - Outpatient treatment for pulmonary embolism. PMID- 22078680 TI - Use of research evidence in practice. PMID- 22078681 TI - Use of research evidence in practice. PMID- 22078682 TI - Use of research evidence in practice. PMID- 22078683 TI - Political will ushers in a new era for tobacco control in Israel. PMID- 22078685 TI - Value-based pricing: time for a NICEr way of measuring health? PMID- 22078686 TI - Effect of reduction in household air pollution on childhood pneumonia in Guatemala (RESPIRE): a randomised controlled trial. AB - BACKGROUND: Pneumonia causes more child deaths than does any other disease. Observational studies have indicated that smoke from household solid fuel is a significant risk factor that affects about half the world's children. We investigated whether an intervention to lower indoor wood smoke emissions would reduce pneumonia in children. METHODS: We undertook a parallel randomised controlled trial in highland Guatemala, in a population using open indoor wood fires for cooking. We randomly assigned 534 households with a pregnant woman or young infant to receive a woodstove with chimney (n=269) or to remain as controls using open woodfires (n=265), by concealed permuted blocks of ten homes. Fieldworkers visited homes every week until children were aged 18 months to record the child's health status. Sick children with cough and fast breathing, or signs of severe illness were referred to study physicians, masked to intervention status, for clinical examination. The primary outcome was physician-diagnosed pneumonia, without use of a chest radiograph. Analysis was by intention to treat (ITT). Infant 48-h carbon monoxide measurements were used for exposure-response analysis after adjustment for covariates. This trial is registered, number ISRCTN29007941. FINDINGS: During 29,125 child-weeks of surveillance of 265 intervention and 253 control children, there were 124 physician-diagnosed pneumonia cases in intervention households and 139 in control households (rate ratio [RR] 0.84, 95% CI 0.63-1.13; p=0.257). After multiple imputation, there were 149 cases in intervention households and 180 in controls (0.78, 0.59-1.06, p=0.095; reduction 22%, 95% CI -6% to 41%). ITT analysis was undertaken for secondary outcomes: all and severe fieldworker-assessed pneumonia; severe (hypoxaemic) physician-diagnosed pneumonia; and radiologically confirmed, RSV negative, and RSV-positive pneumonia, both total and severe. We recorded significant reductions in the intervention group for three severe outcomes fieldworker-assessed, physician-diagnosed, and RSV-negative pneumonia--but not for others. We identified no adverse effects from the intervention. The chimney stove reduced exposure by 50% on average (from 2.2 to 1.1 ppm carbon monoxide), but exposure distributions for the two groups overlapped substantially. In exposure-response analysis, a 50% exposure reduction was significantly associated with physician-diagnosed pneumonia (RR 0.82, 0.70-0.98), the greater precision resulting from less exposure misclassification compared with use of stove type alone in ITT analysis. INTERPRETATION: In a population heavily exposed to wood smoke from cooking, a reduction in exposure achieved with chimney stoves did not significantly reduce physician-diagnosed pneumonia for children younger than 18 months. The significant reduction of a third in severe pneumonia, however, if confirmed, could have important implications for reduction of child mortality. The significant exposure-response associations contribute to causal inference and suggest that stove or fuel interventions producing lower average exposures than these chimney stoves might be needed to substantially reduce pneumonia in populations heavily exposed to biomass fuel air pollution. FUNDING: US National Institute of Environmental Health Sciences and WHO. PMID- 22078687 TI - Fever of unknown origin. PMID- 22078689 TI - The remaining smallpox stocks: the wrong debate? PMID- 22078690 TI - The local burden of emotional disorders. An analysis based on a large health survey in Catalonia (Spain). AB - OBJECTIVE: Mental health conditions are associated with a significant burden on individuals. Using data from a large population health survey, the present study aimed to quantify the burden of emotional disorders (depression and anxiety) on health-related quality of life (HRQoL) in the region of Catalonia (Spain) for evidence-informed policy making. METHODS: Regression models were used to estimate the impact of emotional disorders on HRQoL, controlling by socioeconomic factors and somatic health problems. The rate of emotional disorders was based on the General Health Questionnaire (GHQ-12) and quality of life scores were based on the EQ-5D. RESULTS: The impact of emotional disorders on HRQoL was equal to a reduction of 0.17 in the EQ-5D score. Translation of this individual impact to population figures yielded a total loss of 78,742 quality-adjusted life years (QALYs) for 2006. This strong impact highlights the need for global policies aiming to reduce this burden. CONCLUSION: The negative relation between emotional disorders and the HRQoL of individuals was confirmed and quantified for the population of Catalonia. The use of quality of life scales such as the SF or EQ 5D, combined with data on quasi-specific health conditions provides substantial information for prioritizing and planning health programs. PMID- 22078691 TI - [Introducing the new editor of Reumatologia Clinica]. PMID- 22078692 TI - [Participation of T lymphocytes in the development and perpetuation of rheumatoid arthritis]. PMID- 22078693 TI - [Teaching ultrasonography to Spanish rheumatologists: 15 years of experience]. PMID- 22078694 TI - [2011 Up-date of the consensus statement of the Spanish Society of Rheumatology on osteoporosis]. AB - OBJECTIVE: Due to increasing improvement in the diagnosis, evaluation and management of osteoporosis and the development of new tools and drugs, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and other health professionals involved in the treatment of patients with osteoporosis. METHODS: Recommendations were developed following a nominal group methodology and based on a systematic review. The level of evidence and degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Evidence from previous consensus and available clinical guidelines was used. RESULTS: We have produced recommendations on diagnosis, evaluation and management of osteoporosis. These recommendations include the glucocorticoid-induced osteoporosis, premenopausal and male osteoporosis. CONCLUSIONS: We present the SER recommendations related to the biologic therapy risk management. PMID- 22078695 TI - [Annual trends in knee and hip arthroplasty in rheumatoid arthritis 1998-2007]. AB - OBJECTIVE: To determine the annual number and trend of prostheses implanted in patients with rheumatoid arthritis (RA) at our hospital during the past decade. MATERIALS AND METHODS: Retrospective observational study. Patients were collected through an extensive search of the database of the Clinical Documentation Service between 1998 and 2007. The data was extracted from medical records using a predesigned questionnaire. Statistical analysis of longitudinal prostheses was made by Cochrane's Q test and the Kaplan-Meier method. RESULTS: Sixty-one RA patients were operated on with 78 prostheses as a direct result of their disease at our hospital between 1998 and 2007. Most were women (80%) with positive rheumatoid factor (84%). The mean age was 58 years, and the average time since onset of RA was 13 years. All but one had previously received antirheumatic drugs (88% methotrexate), but only 11% had biological therapy. No changes were observed in the number of arthroplasties as a whole over a decade, although there was a trend towards reduction in the number of patients that required a knee replacement for the first time (Cochrane Q, P=0.05). CONCLUSION: We observed no significant changes in trends in the number of new joint replacement procedures as a whole in the past decade at our hospital, although the number of patients that required knee replacement for the first time as a direct result of their underlying disease seems to have declined in the last decade. PMID- 22078696 TI - [Duration of treatment with etanercept and motives for discontinuation in a cohort of patients with rheumatic disease]. AB - OBJECTIVE: To evaluate the duration of etanercept (ETN) treatment and motives for discontinuation in our local cohort of patients with rheumatic pathology and compare them to the group with other biological treatments. PATIENTS AND METHODS: Prospective observational cohort study. Disease diagnosis, start and end date and motive for discontinuation were recorded. Survival estimation was explored using Kaplan-Meier analysis with remaining patients censored at 1-year, 2-years and 5 years follow-up. RESULTS: Ninety-two (45%) out of 205 patients started ETN treatment. Disease diagnoses recorded were: 48% rheumatoid arthritis, 33% ankylosing spondylitis, 11% psoriatic arthritis, 8% others (juvenile idiopathic arthritis, inflammatory bowel disease related spondylitis, SAPHO syndrome). 52% of patients are still on the drug. The motives for discontinuation were: inefficacy (65%), adverse events (33%) and lack of compliance (2%). Two patients discontinued ETN due to prolonged disease control. Adverse events were: infection (4 patients), post-injection skin reaction (3), uveitis (3), neoplasia (2) and others (3). Using a Kaplan-Meier analysis, at 1-year 64% (CI(95%) 54-74) of patients with ETN treatment had not experienced treatment failure, at 2-years, 59% (48-69) and at 5-years, 43% (30-52). With the rest of biologicals estimated survival was 61% (51-68), 47,5% (40-55) and 23% (10,5-32) respectively. Statistical analysis revealed significant differences (log-rank: P=.024; Breslow: P=.068; Tarone-Ware: P=.040). CONCLUSIONS: In our cohort of patients treated with ETN the estimated survival was better than patients treated with other biological drugs at 1-year, 2-years and 5-years. PMID- 22078698 TI - [Efficacy and safety of abatacept in patients with rheumatoid arthritis and no prior treatment with biologics]. AB - Abatacept (ABA) is a recombinant human fusion protein that blocks co-stimulation signals on T lymphocytes, impeding their activation. Randomized and controlled trials examining efficacy and safety have been performed with ABA combined with methotrexate (MTX), vs MTX monotherapy and vs infliximab (IFB) combined with MTX in patients with Rheumatoid Arthritis and who are naive to biologic therapy. ABA has shown to be more effective than MTX and at least as effective as IFB+MTX, in terms of activity and clinical remission, physical function and reduction in radiological progression. Safety data at 7 years have shown that the drug is comparable to MTX in monotherapy and safer than the IFB+MTX combination, although infections still constitute the main risk when using ABA. This review summarizes the safety and efficacy data of the AIM, ATTEST, Phase IIb IM101-100 and AGREE trials. PMID- 22078697 TI - [Systemic autoimmune diseases and depressive disorders]. AB - INTRODUCTION: The incidence of depression accompanying medical pathologies is elevated and have prognostic importance. OBJECTIVE: To determine the frequency of depression in patients with systemic autoimmune diseases (SAD), as well as to determine the frequency of pain, fatigue and sleep disorders in these patients and their relation with depression. MATERIAL AND METHODS: We performed a descriptive, prospective study on 88 patients with AID. The CES-D depression questionnaire, FSS fatigue questionnaire and the Pittsburgh sleep quality index were administered. RESULTS: 69% (n=61) of patients were depressed. Pain was found in 97% (59/61) of depressed patients and in 62% (17/27) of non-depressed patients (P=.0006). Sleep disorders were found in 95% of depressed patients, whereas 60% of non-depressed patients presented them (P=.00008). Depression was associated with fatigue: 80% (49/61) for depressed and 44% for non-depressed (p=0,001) persons. DISCUSSION: A very elevated prevalence of depression was found in SAD: 69%; constituting the most frequent comorbidity. Depression was significantly associated with pain, fatigue and sleep disorders. PMID- 22078699 TI - [Use of etanercept in amyloidosis secondary to rheumatoid arthritis, a report of two cases]. AB - Rheumatoid arthritis (RA) is one of the most common causes of AA amyloidosis. Most patients are asymptomatic and only when there are large deposits in certain organs, functional problems arise. We report two patients with amyloidosis secondary to RA, with renal and intestinal involvement, who responded to treatment with etanercept. PMID- 22078701 TI - [Unilateral generalized morphea: a case and literature review]. AB - Localized scleroderma is a connective tissue disorder generally involving de entire dermis and usually limited to the subcutaneous tissue; however, it may progress to large indurated plaques, growth retardation, muscle atrophy, and even to flexion deformities or poorly healing ulcers. Unilateral generalized morphea is an extremely rare variant of localized scleroderma which has seldom been reported in the literature. We report the case of a girl who developed unilateral generalized morphea on the right side of the body. PMID- 22078700 TI - [Meningeal and Guillain-Barre syndrome in a patient with rheumatoid arthritis receiving adalimumab therapy]. AB - Adalimumab is a recombinant human monoclonal antibody that blocks the effects of tumor necrosis factor-alpha, and is presently used for treatment of rheumatoid arthritis, with demyelination being a potential adverse effect. A 31 year-old male with seropositive rheumatoid arthritis presented with diarrhea after the second injection of adalimumab. He was treated with ciprofloxacin. In a few days he developed a Guillain-Barre syndrome confirmed by electromyography, and his cerebrospinal fluid was compatible with meningeal syndrome or partially treated bacterial meningitis. Adalimumab may be associated with the development of demyelination and infectious diseases. Moreover, both the central nervous system and the peripheral nervous system can be affected. PMID- 22078702 TI - [Glucocorticoids in rheumatoid arthritis: almost always or hardly ever?]. AB - The use of glucocorticoids in rheumatoid arthritis has been the source of frequent debate in the last decades. There is evidence on its anti-inflammatory capacity and its power to decrease radiologic progression, particularly if used in recent onset rheumatoid arthritis. However, there are still some voices questioning its use. Their arguments are its potential side-effects, especially when the glucocorticoids are used in high doses and/or for extended periods of time. In this review, we will try to summarize the evidence regarding this issue, from the beginning of the discussion in the fifties to the last releases. PMID- 22078703 TI - [Vaccines and chemo-prophylaxis in rhemautoid arthritis: is a vaccine calendar necessary?]. AB - Patients with rheumatoid arthritis (RA) are at increased risk of infection compared to healthy individuals. The increased risk may be associated with the underlying disease, comorbidities and immunosuppressive therapy required to control RA activity. In several recent studies, influenza, pneumococcal and hepatitis B vaccines administered to RA patients were reported to be safe and serologically effective. However, several lines of evidence suggest a possible aberrant immunologic response following vaccination due to the compromised immunity of these patients. Therefore, vaccination of RA patients prior to immunosuppressive treatment may serve as an alternative prophylactic approach and should be considered for future investigation. Besides, prophylactic health measures should be taken to avoid latent chronic infections as tuberculosis and hepatitis B, during therapy with biological agents. PMID- 22078704 TI - [Tuberculous arthritis in a 2 year old toddler]. PMID- 22078705 TI - [Ischiopubic pain in a patient with Paget's disease]. PMID- 22078706 TI - [Introduction of a day-care hospital model: proposals for measures that guarantee the specific needs of rheumatology services in the Community of Valencia (Spain)]. PMID- 22078707 TI - TRIM5alpha associates with proteasomal subunits in cells while in complex with HIV-1 virions. AB - BACKGROUND: The TRIM5 proteins are cellular restriction factors that prevent retroviral infection in a species-specific manner. Multiple experiments indicate that restriction activity requires accessory host factors, including E2-enzymes. To better understand the mechanism of restriction, we conducted yeast-two hybrid screens to identify proteins that bind to two TRIM5 orthologues. RESULTS: The only cDNAs that scored on repeat testing with both TRIM5 orthologues were the proteasome subunit PSMC2 and ubiquitin. Using co-immunoprecipitation assays, we demonstrated an interaction between TRIM5alpha and PSMC2, as well as numerous other proteasome subunits. Fluorescence microscopy revealed co-localization of proteasomes and TRIM5alpha cytoplasmic bodies. Forster resonance energy transfer (FRET) analysis indicated that the interaction between TRIM5 and PSMC2 was direct. Previous imaging experiments demonstrated that, when cells are challenged with fluorescently-labeled HIV-1 virions, restrictive TRIM5alpha orthologues assemble cytoplasmic bodies around incoming virion particles. Following virus challenge, we observed localization of proteasome subunits to rhTRIM5alpha cytoplasmic bodies that contained fluorescently labeled HIV-1 virions. CONCLUSIONS: Taken together, the results presented here suggest that localization of the proteasome to TRIM5alpha cytoplasmic bodies makes an important contribution to TRIM5alpha-mediated restriction. PMID- 22078708 TI - miRNA profiling for biomarker discovery in multiple sclerosis: from microarray to deep sequencing. AB - MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. miRNAs are highly expressed in cells of the immune and nervous system, attesting to their importance in Neuroimmunology. Besides their involvement in modulation of physiological and pathological processes, miRNAs hold high promise as disease biomarkers, therapeutic agents and/or drug targets. Several studies have recently explored the involvement of miRNAs in Multiple Sclerosis (MS) using a variety of miRNA profiling techniques. In this review, we discuss basic miRNA biology and nomenclature, the techniques available for miRNA profiling research and recent miRNA profiling studies in Multiple Sclerosis. PMID- 22078709 TI - Role of gammadelta T cells in West Nile virus-induced encephalitis: friend or foe? AB - West Nile virus (WNV)-induced encephalitis has been a public health concern in North America over the past decade. No therapeutics or vaccines are available for human use. Studies in animal models have provided important information for investigations of WNV pathogenesis and the host immune response in humans. This article will give an overview of the role of gammadelta T cells, one of the non classical T cell subsets in the murine model of WNV encephalitis. PMID- 22078710 TI - Late reoperations after repaired acute type A aortic dissection. AB - OBJECTIVE: Late complications can develop in patients after surgery for aortic type A dissection, mandating redo surgery on the ascending aorta and arch. METHODS: From 2006 to 2010, 23 patients (aged 41-69 years) who had late complications related to previous aortic surgery for acute type A dissection underwent redo surgery. Initial surgery included ascending aorta replacement in all cases. RESULTS: The main indications for reoperation were progressive enlargement of the false lumen of the aortic arch or descending aorta and suture line dehiscence in 10 patients each. All patients with progressive aneurysm formation in nonresected aortic segments had persistent dissection within the aortic arch since initial surgery. Suture line dehiscence led to a localized hematoma in most cases. Three patients presented with graft infection and extensive perigraft hematoma. The average time interval from the initial repair to the redo procedure was 71+/-56 months. Exchange of the formerly implanted Dacron graft in the ascending aorta was the most frequently used surgical procedure. Implantation of a valved conduit was deemed necessary in 4 cases, and isolated aortic valve replacement was necessary in 2 cases. A hybrid stent graft was used in 6 patients. All patients survived surgery, and 1 patient died of postoperative low output cardiac failure in hospital. Only 1 major stroke was noted. CONCLUSIONS: Complex reoperations for repaired acute type A dissection can be performed safely. The concern for the reoperative risk should not dictate the operative strategy during the initial procedure in acute type A dissection. PMID- 22078711 TI - Changes in left atrioventricular valve geometry after surgical repair of complete atrioventricular canal. AB - OBJECTIVE: The most common reason for late surgical reintervention after repair of complete atrioventricular canal defects is the development of left atrioventricular valve regurgitation. We sought to determine the changes in left atrioventricular valve geometry after surgical repair that may predispose to regurgitation. METHODS: Atrioventricular valve measurements were obtained by 2 dimensional echocardiography at 3 different time points (preoperative, early postoperative, and midterm postoperative [6-12 months]). Left atrioventricular valve annulus area and left ventricular volume were calculated; vena contracta of the regurgitant jet orifice was measured. All measurements were normalized relative to an appropriate power of body surface area. RESULTS: From January 2000 to January 2008, 101 patients with complete atrioventricular canal repair were included. Left atrioventricular valve annulus was noted to remodel from an elliptical shape to a circular shape after surgery. Left atrioventricular valve annulus area increased early postoperatively (systole: 4.1 +/- 0.2 cm(2)/m(2) vs 6.1 +/- 0.3 cm(2)/m(2), P < .001; diastole: 7.2 +/- 0.4 cm(2)/m(2) vs 10.0 +/- 0.5 cm(2)/m(2), P < .001, pre- vs postoperative, respectively). This increase was sustained in the midterm postoperative period (systole: 6.1 +/- 0.3 cm(2)/m(2), P = .85, vs diastole: 10.0 +/- 0.4 cm(2)/m(2), P = .78, early vs midterm postoperative). Left ventricular volume increased in the early and midterm postoperative periods compared with preoperative (systole: 16.9 +/- 1.2 mL/m(2) vs 26.2 +/- 1.7 mL/m(2), P < .001; diastole: 35.0 +/- 2.4 mL/m(2) vs 52.5 +/- 3.2 mL/m(2), P < .001). CONCLUSIONS: Complete atrioventricular canal repair leads to left atrioventricular valve annular shape change with increased area and circular shape. The change in left atrioventricular valve annulus shape appeared to be mainly due to increased circumference in the posterior free wall of the annulus. These findings may provide a mechanism for the progression of central regurgitation seen after complete atrioventricular canal repair and a potential solution. PMID- 22078712 TI - Qualitative description of college students' dinner groups. AB - OBJECTIVE: To discover how college students conduct dinner groups and perceptions of the benefits and difficulties of participation. DESIGN: Qualitative study conducted with 7 focus groups. SETTING AND PARTICIPANTS: A university campus, with 36 students participating in dinner groups, defined as a group of 3 people or more cooking for one another (or together) and eating together at least 4 times a week. MAIN OUTCOME MEASURE: Dinner groups. ANALYSIS: The focus group recordings were transcribed, coded, and reconciled. NUDIST NVivo software (version 8, QSR International, Victoria, Australia, 2008) assisted in coding data to identify themes and subthemes. RESULTS: Dinner groups were composed of roommates or students living nearby. They rotated who made each dinner. Benefits identified included social interaction, increasing confidence in cooking, saving money and time, and eating more varied and healthful foods. Difficulties, which were uncommon, included increased time spent on days the student cooked and stresses related to cooking on a schedule. Students found that the benefits far outweighed the difficulties and universally wanted to continue in a dinner group. CONCLUSIONS AND IMPLICATIONS: College students enjoyed dinner groups, and promoting them may be an option for improving college students' eating habits. Nearly all students believed that they ate better in a dinner group, but research is needed to assess actual intake. PMID- 22078713 TI - Biological versus cultural evolution: beyond a false dichotomy. Comment on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22078714 TI - Extracranial primary and secondary meningiomas. AB - Meningioma is a well-recognized tumour of the central nervous system. However, extracranial non-dural or ectopic meningiomas are rare and in most of the reported cases, meningiomas are diagnosed only after histopathologic examination. Over the last 5 years, the authors have seen three cases. In these case reports, they discuss the salient features of these lesions, which can aid the preoperative diagnosis and management of these patients. One of the cases is a rarity, owing to the extreme extracranial position which allowed the pressure of the tumour abrade the adjacent structures. In one case, reconstruction of the skull bone using polymeric materials (Acrylic matter) was necessary. In the other two cases, titanium plates and screws were used to reconstruct the jaw. PMID- 22078715 TI - Editorial. PMID- 22078717 TI - A comparison of integrated and discrete depth sampling for monitoring toxic species of Dinophysis. AB - Dinophysis acuminata and Dinophysis acuta produce lipophilic toxins that cause most shellfish harvesting closures in the Atlantic coastal waters of Europe. Dinophysis often exhibit patchy distributions and sampling with conventional methods may fail to detect them. A 6-month calibration study in 2006, plus an additional sampling in 2010 were carried out in Galicia to compare Dinophysis counts obtained from weekly high vertical resolution bottle samples with depth integrated hose samples. Counts with these two methods were comparable at some depth-ranges, but hose maxima were over one order of magnitude lower under thin layer scenarios. Estimates from hose samplers should be used with caution in programmes using a "Dinophysis index", either to trigger shellfish sampling or to establish precautionary harvesting closures. In general, hose samplers provide reliable information on the occurrence of Dinophysis except under extreme site specific hydrodynamic conditions. This study adds new information about the heterogeneous, specific vertical distributions of two Dinophysis spp. PMID- 22078716 TI - Lupus nephritis: current update. AB - Lupus nephritis is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. The general consensus is that 60% of lupus patients will develop clinically relevant nephritis at some time in the course of their illness. Prompt recognition and treatment of renal disease is important, as early response to therapy is correlated with better outcome. The present review summarizes our current understanding of the pathogenic mechanisms underlying lupus nephritis and how the disease is currently diagnosed and treated. PMID- 22078718 TI - High prevalence of hyperglycaemia and the impact of high household income in transforming rural China. AB - BACKGROUND: The prevalence of hyperglycaemia and its association with socioeconomic factors have been well studied in developed countries, however, little is known about them in transforming rural China. METHODS: A cross sectional study was carried out in 4 rural communities of Deqing County located in East China in 2006-07, including 4,506 subjects aged 18 to 64 years. Fasting plasma glucose (FPG) was measured. Subjects were considered to have impaired fasting glucose (IFG) if FPG was in the range from 5.6 to 6.9 mmol/L and to have diabetes mellitus (DM) if FG was 7.0 mmol/L or above. RESULTS: The crude prevalences of IFG and DM were 5.4% and 2.2%, respectively. The average ratio of IFG/DM was 2.5, and tended to be higher for those under the age of 35 years than older subjects. After adjustment for covariates including age (continuous), sex, BMI (continuous), smoking, alcohol drinking, and regular leisure physical activity, subjects in the high household income group had a significantly higher risk of IFG compared with the medium household income group (OR: 1.74, 95% CI: 1.11-2.72) and no significant difference in IFG was observed between the low and medium household income groups. Education and farmer occupation were not significantly associated with IFG. CONCLUSIONS: High household income was significantly associated with an increased risk of IFG. A high ratio of IFG/DM suggests a high risk of diabetes in foreseeable future in the Chinese transforming rural communities. PMID- 22078719 TI - Assessment of the burden of influenza in children. PMID- 22078720 TI - Community management of severe pneumonia in children. PMID- 22078721 TI - Community case management of severe pneumonia with oral amoxicillin in children aged 2-59 months in Haripur district, Pakistan: a cluster randomised trial. AB - BACKGROUND: First dose oral co-trimoxazole and referral are recommended for WHO defined severe pneumonia. Difficulties with referral compliance are reported in many low-resource settings, resulting in low access to appropriate treatment. The objective in this study was to assess whether community case management by lady health workers (LHWs) with oral amoxicillin in children with severe pneumonia was equivalent to current standard of care. METHODS: In Haripur district, Pakistan, 28 clusters were randomly assigned with stratification in a 1:1 ratio to intervention and control clusters by use of a computer-generated randomisation sequence. Children were included in the study if they were aged 2-59 months with WHO-defined severe pneumonia and living in the study area. In the intervention clusters, community-based LHWs provided mothers with oral amoxicillin (80-90 mg/kg per day or 375 mg twice a day for infants aged 2-11 months and 625 mg twice a day for those aged 12-59 months) with specific guidance on its use. In control clusters, LHWs gave the first dose of oral co-trimoxazole (age 2-11 months, sulfamethoxazole 200 mg plus trimethoprim 40 mg; age 12 months to 5 years, sulfamethoxazole 300 mg plus trimethoprim 60 mg) and referred the children to a health facility for standard of care. Participants, carers, and assessors were not masked to treatment assignment. The primary outcome was treatment failure by day 6. Analysis was per protocol with adjustment for clustering within groups by use of generalised estimating equations. This study is registered, number ISRCTN10618300. FINDINGS: We assigned 1995 children to treatment in 14 intervention clusters and 1477 in 14 control clusters, and we analysed 1857 and 1354 children, respectively. Cluster-adjusted treatment failure rates by day 6 were significantly reduced in the intervention clusters (165 [9%] vs 241 [18%], risk difference -8.9%, 95% CI -12.4 to -5.4). Further adjustment for baseline covariates made little difference (-7.3%, -10.1 to -4.5). Two deaths were reported in the control clusters and one in the intervention cluster. Most of the risk reduction was in the occurrence of fever and lower chest indrawing on day 3 (-6.7%, -10.0 to -3.3). Adverse events were diarrhoea (n=4) and skin rash (n=1) in the intervention clusters and diarrhoea (n=3) in the control clusters. INTERPRETATION: Community case management could result in a standardised treatment for children with severe pneumonia, reduce delay in treatment initiation, and reduce the costs for families and health-care systems. FUNDING: United States Agency for International Development (USAID). PMID- 22078722 TI - A pilot programme of organ donation after cardiac death in China. AB - China's aims are to develop an ethical and sustainable organ transplantation system for the Chinese people and to be accepted as a responsible member of the international transplantation community. In 2007, China implemented the Regulation on Human Organ Transplantation, which was the first step towards the establishment of a voluntary organ donation system. Although progress has been made, several ethical and legal issues associated with transplantation in China remain, including the use of organs from executed prisoners, organ scarcity, the illegal organ trade, and transplantation tourism. In this Health Policy article we outline the standards used to define cardiac death in China and a legal and procedural framework for an organ donation system based on voluntary donation after cardiac death that adheres to both China's social and cultural principles and international transplantation standards. PMID- 22078723 TI - Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. AB - BACKGROUND: The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years. METHODS: We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. FINDINGS: We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. INTERPRETATION: Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. FUNDING: WHO; Bill & Melinda Gates Foundation. PMID- 22078724 TI - Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2. AB - BACKGROUND: Chronic hemodynamic overloading leads to heart failure (HF) due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto caval fistula (ACF) and sham-operated rats harvested at the advanced, decompensated stage of HF. METHODS: We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip. RESULTS: In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs. CONCLUSIONS: The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy. PMID- 22078725 TI - [Sudden decrease in visual acuity and pulmonary infiltrates]. PMID- 22078726 TI - [Clinical management of acute and chronic human immunodeficiency virus infection before starting antiretroviral treatment]. AB - The evaluation of new cases of HIV infection is relatively common in Spain, where several thousands of patients with new infections are diagnosed each year. Eighty per cent of them have a chronic HIV infection at the first clinical evaluation, which is symptomatic (late presenters) in up to 30% of patients. The initial evaluation of HIV infection is not only directed at determining the clinical, virological (plasma HIV RNA viral load, resistance test and viral tropism) and immunological (CD4+ T-cell cell count) situation of the patients, but must also address the study of their co-infections (hepatitis, tuberculosis) and comorbidities (cardiovascular, hepatic, renal and bone) and the risk of HIV transmission. This is needed in order to decide, whether or not to start antiretroviral treatment, and with which combined antiretroviral treatment to start with, the prophylaxis of opportunistic infections, and the treatment of coinfections and comorbidities. The past and current medical history, the physical examination and laboratory tests will help us decide if the patient is to receive therapeutic intervention. The level of CD4+ T-cell lymphocytes is the best marker to suggest when to start combined antiretroviral treatment, indicating whether or not to start prophylaxis against opportunistic infections (if patients have a CD4+ T-cell count below 200 cells/mm(3)), and in advanced patients should make us suspect the presence of active opportunistic diseases in symptomatic cases. The management of patients with HIV infection must also include appropriate health education on the modes of transmission and prevention of HIV infection, and also to explain its natural history and how it can be modified with proper antiretroviral treatment, as well as to promote a healthy life. No less important is the psychological support, as these patients must learn to live with a chronic infection, which managed properly can ensure a very good long-term prognosis and quality of life. PMID- 22078727 TI - Combining microRNA-449a/b with a HDAC inhibitor has a synergistic effect on growth arrest in lung cancer. AB - Histone deacetylases (HDACs) play a crucial role in tumorigenesis. Over expression of HDACs has been reported in lung cancer. The mechanism of highly expressed HDAC1 in lung cancer has yet not been determined. In the present study, we showed that miR-449a/b regulates HDAC1 by directly binding with the 3' untranslated region of the HDAC1. The expression of miR-449a/b was down-regulated and the expression of HDAC1 was up-regulated in primary lung cancer. The down expression of miR-449a/b might be one mechanism for over-expression of HDAC1 in lung cancer. miR-449a/b inhibited cell growth and anchorage-independent growth. Furthermore, co-treatment with miR-449a and HDAC inhibitors had a significant growth reduction compared with HDAC inhibitor mono-treatment. These results suggest that miR-449a/b may have a tumor suppressor function and might be a potential therapeutic candidate in patients with primary lung cancer. PMID- 22078728 TI - Sympathetic skin response (SSR) in multiple sclerosis and clinically isolated syndrome: a case-control study. AB - OBJECTIVE: To compare the sympathetic skin responses (SSRs) in patients with multiple sclerosis (MS), clinically isolated syndrome (CIS), and healthy controls. METHODS: SSR was recorded on both hands and feet in 30 patients and 20 healthy controls. SSR results (latency measurements) were compared in patients with normal or abnormal brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs). RESULTS: Twenty-three (76.6%) and sixteen patients (53.3%) with MS had abnormal SSR recordings based on 2-standard deviation (SD) or 3-SD (from the mean of the control group) abnormality criteria, respectively. Sixty-six percent and 40 percent of patients had abnormal (>2SD) SSR in at least one hand and one foot, respectively. Patients with absent SSR had more severe disease and higher Expanded Disability Status Scale (EDSS) scores. Fourteen patients had an EDSS of zero, of whom nine had abnormal SSR and others had at least one abnormal EP study. Patients with abnormal SSR had significantly more abnormal BAEPs and SEPs than patients with normal SSR. SSR latencies were significantly correlated with EDSS and disease duration (P<0.01). All patients had at least one abnormal electrophysiological study. ROC-curve analysis showed that a cut-off score of 7008 ms as the sum of all-4-limb SSR latencies had a 80% sensitivity and 95% specificity for differentiating MS patients from healthy controls. CONCLUSIONS: This study suggests that SSR is a useful tool for assessment of autonomic function and can be complementary to EDSS and other electrophysiological studies in patients with MS and CIS. PMID- 22078729 TI - A new electrode placement for recording the compound motor action potential of the first dorsal interosseous muscle. AB - OBJECTIVE: This paper describes a new electrode placement for recording compound muscle action potentials (CMAPs) of the first dorsal interosseous muscle (FDI) to determine the distal motor latency (DML) and study nerve conduction of the ulnar nerve across the wrist. METHODS: The DML to the FDI was evaluated bilaterally in 90 subjects after stimulation 1cm proximal to the distal wrist crease and at the palm. The CMAP was recorded with a pair of disposable surface electrodes fixed over the FDI and wrist. RESULTS: The CMAP never exhibited a positive initial deflection, with a gain of 0.5 mV per division. DML to the FDI was 2.65+/-0.26 ms (mean+/-SD), and CMAP amplitude was 14.7+/-3.3 mV. A prolonged DML was taken as 3.4 ms (mean+3 standard deviation [SD]). CONCLUSIONS: This new electrode placement offers more reproducible results for determining the DML to the FDI as it provides the shortest DML, and the tightest SD values. SIGNIFICANCE: This result is obtained through the respect of fundamental rules for CMAP recording, as it shows no positive wave at the onset of the CMAP of the FDI. Its use should improve the diagnosis of ulnar nerve lesions at the wrist and more especially of the deep motor branch. PMID- 22078730 TI - Repeatability and variability of baropodometric and spatio-temporal gait parameters--results in healthy subjects and in stroke patients. AB - AIMS OF THE STUDY: Our purpose was to determine the repeatability and variability of baropodometric and spatio-temporal gait parameters in both hemiparetic patients and healthy subjects. HYPOTHESIS: parameters with a good repeatability and a low variability could be used to follow gait evolution. POPULATION AND METHOD: Twelve stroke patients and 10 healthy subjects were included. Each participant performed trials (F-Scan(r) system and Bessou Locometer) at 48 h intervals under identical conditions. The following parameters were analyzed: displacement of the center of pressure (COP), peaks of pressure under forefoot and hindfoot, step length, single and double support time, and walking velocity. Comparisons were made within and between sessions, inter-trials and between sides. RESULTS: Neither visit effects in either population nor side effects in healthy subjects were observed. Repeatability assessed by the intraclass correlation coefficient ("ICC agreement" ICC) was excellent to adequate overtime for anterior-posterior (AP) displacement of the COP, step length, simple support time and walking velocity in both hemiparetic patients (ICC 0.92; 0.84; 0.91; 0.94) and healthy subjects (ICC 0.85; 0.44; 0.64; 0.56). The coefficient of variation (CV) was low in paretic side for AP and single support time, and at a less degree for the lateral deviation of the COP (ML) and the posterior margin (PM). CONCLUSION: In this study, baropodometric (AP and PM) and spatio-temporal gait (step length, single support time and walking velocity) parameters were found to show good repeatability overtime; these parameters are the ones most likely to be useful in assessing the effects of treatments that are proposed to improve gait in stroke patients. PMID- 22078731 TI - Obstructive sleep apnoea syndrome: comparison between polysomnography and portable sleep monitoring based on jaw recordings. AB - INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) constitutes a new major public health problem because of its several pathophysiologic consequences such as cognitive disorders, excessive daytime sleepiness with risks of traffic accidents, cardiovascular implications, and decrease of quality of life. The necessity of a gold-standard polysomnography to ensure an accurate diagnosis implies an expensive, technical and time-consuming examination. Thus, it seems logical to develop new systems so as to diagnose SAS and to make it possible to detect apnoeas/hypopnoeas easily during sleep even at home. AIM OF THE STUDY: To assess a novel type-3 portable monitoring (PM) device, the Somnolter, and dedicated automatic analysis of several signals, one of which is the mandibular movement signal. METHOD: We studied patients suffering from OSAS. For all the patients, a nocturnal diagnosis polysomnography (PSG) was recorded in hospital settings, based on six EEG channels, two EOG channels, chin EMG channel, EKG, and respiratory parameters. At the same time, the Somnolter PM device recorded the physiological parameters from its own nasal prongs, thoracic belt, pulse oxymeter, body position, and jaw movement sensors. A visual analysis of PSG recordings was made leading to the detection of apnoea/hypopnoea index (AHI-PSG) and an automatic analysis of the Somnolter traces was performed to get automatic apnoea/hypopnoea index (AHI-A). The added value of the mandible movement signals was the particular jaw movements related to arousals, to respiratory efforts and to sleep/wake state. A comparison was made between the automatic and gold AHIs standard and the correlation was calculated between them. RESULTS: Ninety patients, aged between 47 and 70 years (mean age: 55.4+/-8.7) took part in the study. The linear regression and the correlation coefficient between AHI-PSG and AHI-A showed the good reliability of the automatic method. The Bland Altman analysis shows a correlation of 0.95 with a sensitivity of 83.6 and specificity of 81.8. CONCLUSION: The dedicated automatic analysis based on mandibular movements presents a good potential for the diagnosis of OSAS. The AHI computed by the automatic method is correlated with the AHI-PSG and the Somnolter could easily be used both in hospital, and in ambulatory settings. PMID- 22078732 TI - Millard the magician. PMID- 22078733 TI - A new era for lignocellulosics utilization through biotechnology. PMID- 22078734 TI - Low impact strategies to improve ligninolytic enzyme production in filamentous fungi: the case of laccase in Pleurotus ostreatus. AB - The ever-increasing demand of laccases for biodelignification, industrial oxidative processes and environmental bioremediation requires the production of large quantities of enzymes at low cost. The present work was carried out to reduce laccase production costs in liquid fermentations of the white-rot fungus Pleurotus ostreatus through two different approaches. In the first, screening of fungal spent media as natural laccase inducer was performed, eliminating the presence of potentially toxic/recalcitrant and expensive exogenous inducers in the culture broth. In the latter, breeding of different strains of P. ostreatus, screened for their laccase productivity, was performed by cross-hybridisation, avoiding genetic transformation and mutagenic treatments that could produce organisms not suitable for "natural or safe processes". A laccase production level close to 80,000U/L by combining the two approaches was achieved. Autoinduction and classical breeding represent promising tools for the improvement of fungal fermentation without affecting the disposable costs that also depend on the eco-compatibility of the whole process. PMID- 22078735 TI - Fungal laccases: versatile tools for lignocellulose transformation. AB - Conversion of lignocellulosic materials to useful, high value products normally requires a pre-treatment step to transform or deconstruct the recalcitrant and heterogeneous lignin fraction. The development of "green tools" for the transformation of lignocellulosic feedstocks is in high demand for a sustainable exploitation of such resources. This multi-faceted challenge is being addressed by an ever-increasing suite of ligninolytic enzymes isolated from various sources. Among these, fungal laccases are known to play an important role in lignin degradation/modification processes. The white-rot fungus Pleurotus ostreatus expresses multiple laccase genes encoding isoenzymes with different properties. The availability of established recombinant expression systems for P. ostreatus laccase isoenzymes has allowed to further enrich the panel of P. ostreatus laccases by the construction of mutated, "better performing" enzymes through molecular evolution techniques. New oxidative catalysts with improved activity and stability either at high temperature and at acidic and alkaline pH have been isolated and characterized. PMID- 22078736 TI - Pleurotus ostreatus heme peroxidases: an in silico analysis from the genome sequence to the enzyme molecular structure. AB - An exhaustive screening of the Pleurotus ostreatus genome was performed to search for nucleotide sequences of heme peroxidases in this white-rot fungus, which could be useful for different biotechnological applications. After sequence identification and manual curation of the corresponding genes and cDNAs, the deduced amino acid sequences were converted into structural homology models. A comparative study of these sequences and their structural models with those of known fungal peroxidases revealed the complete inventory of heme peroxidases of this fungus. This consists of cytochrome c peroxidase and ligninolytic peroxidases, including manganese peroxidase and versatile peroxidase but not lignin peroxidase, as representative of the "classical" superfamily of plant, fungal, and bacterial peroxidases; and members of two relatively "new" peroxidase superfamilies, namely heme-thiolate peroxidases, here described for the first time in a fungus from the genus Pleurotus, and dye-decolorizing peroxidases, already known in P. ostreatus but still to be thoroughly explored and characterized. PMID- 22078737 TI - Transcription analysis of lignocellulolytic enzymes of Penicillium decumbens 114 2 and its catabolite-repression-resistant mutant. AB - Penicillium decumbens 114-2 is a fast-growing filamentous fungus which secretes a variety of lignocellulolytic enzymes. Its catabolite-repression-resistant mutant JU-A10 with high secretion capacity of cellulolytic enzymes has been used industrially for biomass hydrolysis. Transcription levels of 6 important lignocellulolytic enzymes genes (cel5A, cel6A, cel7A, cel7B, xyn10A, and xyn11A) from both strains were determined on different carbon sources (glucose, sorbose, lactose, cellobiose, cellulose, and cellulose-wheat bran), by means of a real time quantitative polymerase chain reaction. For both strains, the 6 genes are coordinately regulated at transcriptional level. Glucose and cellobiose repressed whereas cellulose and cellulose-wheat bran induced expression of 6 genes in both strains. Expression levels of all genes tested in the mutant strain JU-A10 were substantially higher than those in wild-type strain 114-2 on all carbon sources. On glucose repression condition, the mutant JU-A10 appeared obviously derepressed. Lactose was first proved to have an inductive effect on lignocellulolytic enzyme genes expression at lower concentration in Penicillium spp. PMID- 22078738 TI - Mechanism of the positive effect of poly(ethylene glycol) addition in enzymatic hydrolysis of steam pretreated lignocelluloses. AB - The efficiency of enzymatic hydrolysis of lignocellulses can be increased by addition of surfactants and polymers, such as poly(ethylene glycol) (PEG). The effect of PEG addition on the cellulase adsorption was tested on various steam pretreated lignocellulose substrates (spruce, willow, hemp, corn stover, wheat straw, sweet sorghum bagasse). A positive effect of PEG addition was observed, as protein adsorption has decreased and free enzyme activities (FP, beta glucosidase) have increased due to the additive. However, the degree of enhancement differed among the substrates, being highest on steam pretreated spruce. Results of lignin analysis (pyrolysis-GC/MS, (31)P NMR) suggest that the effect of PEG addition is in connection with the amount of unsubstituted phenolic hydroxyl groups of lignin in the substrate. Adsorption experiments using two commercial enzyme preparations, Celluclast 1.5L (Trichoderma reesei cellulase) and Novozym 188 (Aspergillus niger beta-glucosidase) suggested that enzyme origins affected on the adsorptivity of beta-glucosidases. PMID- 22078739 TI - Impact of epiphytic and endogenous enzyme activities of senescent maize leaves and roots on the soil biodegradation process. AB - This study was focused on investigating the role of the initial residue community, i.e. microorganisms and enzymes from the epiphytic and endophytic compartments, in soil decomposition processes. Aerial and underground parts (leaves and roots) of maize (Zea mays L.) plants were gamma-irradiated, surface sterilized with sodium hypochlorite (NaOCl)/ethanol or non-sterilized (controls), while the outer surface morphology of maize leaves and roots was examined by scanning electron microscopy (SEM). Non-sterilized and sterilized maize leaves and roots were incubated in soil to study carbon (C) mineralization kinetics and enzyme dynamics (L-leucine aminopeptidase, CBH-1, xylanase, cellulase and laccase). SEM results showed that initial microbial colonization was more pronounced on non-sterilized leaf and root surfaces than on sterilized samples. The hypochlorite treatment removed a part of the soluble components of leaves by washing and no specific effect of any type of colonizing microorganisms was observed on C mineralization. In contrast, gamma irradiation and hypochlorite treatments did not affect root chemical characteristics and the quantitative effect of initial residue-colonizing microorganisms on C mineralization was demonstrated. The variations in C mineralization and enzyme dynamics between non sterilized and sterilized roots suggested that activities of epiphytic and endogenic microorganisms were of the same order of magnitude. PMID- 22078740 TI - Structure and optical properties of plant cell wall bio-inspired materials: cellulose-lignin multilayer nanocomposites. AB - Interfacial affinity between lignin model compound (dehydrogenation polymer [DHP]) and cellulose nanocristals (CN) was studied before building a nanocomposite cellulose/lignin in multilayer form by spin-coating method. The adsorption isotherm of DHP was measured by ellipsometry at the liquid/CN film interface and showed that the surface concentration of adsorbed DHP increases with the bulk concentration in solution. The DHP appeared as globular structures on cellulosic film, as observed by AFM. Spreading a dense lignin layer on CN film gave rise to the disappearance of the InfraRed resonance bands related to the DHP aromatics. The film obtained from alternate layers of cellulose/DHP was transparent in visible light and had weak absorption in UV wavelengths. Optical properties measured in the visible wavelength range by ellipsometry and spectrophotometry indicated that beyond six bilayers (cellulose/DHP), the composite exhibits antireflexion properties. PMID- 22078741 TI - Saccharification of Miscanthus x giganteus, incorporation of lignocellulosic by product in cementitious matrix. AB - Given the non competition of miscanthus with food and animal feed, this lignocellulosic species has attracted attention as a possible biofuel resource. However, sustainability of ethanol production from lignocelluloses biomass would imply reduction in the consumption of chemicals and/or energetic means, but also valorization of the lignocellulosic by-product remaining from enzymatic saccharification. Introduction of these by-products into a cementitious matrix could be used in manufacturing a lightweight composite. Miscanthus biomass was submitted to chemical pretreatments followed by saccharification using an enzymatic cocktail. Residues from saccharification were then mixed with a cementitious matrix. Given their mechanical properties and a good adherence between cement and by-product, the hardened materials could be used. However, the delay in the beginning of setting time is too long, which prevents the direct use of by-product into cementitious matrix. Preliminary experiments using a setting accelerator in the cementitious matrix permitted significant reduction in the setting time delay. PMID- 22078742 TI - [Lung transplantation in internal medicine]. PMID- 22078743 TI - Congenital hairy polyp of the soft palate. AB - Hairy polyp is an unusual developmental malformation that is most frequently seen as a pedunculated tumor in the neonate. They are benign lesions containing elements of both ectodermal and mesodermal origin. The symptoms of hairy polyps relate both to their location and their size. Larger lesions produce symptoms due to feeding difficulties and airway obstruction while smaller lesions cause intermittent symptoms resulting from a ball-valve type of obstruction. We present two cases of a soft palate hairy polyp causing respiratory and feeding difficulties and review the literature. PMID- 22078744 TI - EXIT (Ex utero Intrapartum Treatment) in lymphatic malformations of the head and neck: discussion of three cases and proposal of an EXIT-TTP (Team Time Procedure) list. AB - OBJECTIVES: Ex utero Intrapartum Treatment (EXIT) is a technique to secure the fetal airway while oxygenation is maintained through utero-placental circulation. The aim of the study is to present three cases of fetal lymphatic malformation of the head and neck that required EXIT and to summarize EXIT details. METHODS: The cases were studied before the delivery and EXIT was planned with a multidisciplinary team. The key factors of EXIT are considered and the type, stage and clinical score of the three lymphatic malformations are defined. RESULTS: In the three cases of EXIT the time working on placental support to secure the airway was 9, 7, and 9 min, respectively (from the hysterotomy to clamping the umbilical cord). Procedures performed on the airway were laryngo tracheo-bronchoscopy in the first case, laryngoscopy and intubation in the second one, laryngoscopy, drainage of the lymphatic macro-cyst, and intubation in the third case. A sketching to detail the EXIT steps are presented: EXIT-Team Time Procedure list (EXIT-TTP list). Lymphatic malformations were classified as mixed (micro/macro-cystic) in two cases, and macro-cystic in one. de Serres Stage was IV, V and II. Therapy varied in the three neonates (surgery alone, surgery+Picibanil+Nd-YAG, or Picibanil alone). CONCLUSIONS: In case of prenatal suspicion of airway obstruction, EXIT should be planned with a multidisciplinary team. The EXIT-Team Time Procedure list (EXIT-TTP list), reviews the most critical phases of the procedure when different teams are working together. The type of lymphatic malformation, the anatomic location and the clinical score predict the outcome. PMID- 22078745 TI - Functional neuroanatomy of vocalization in patients with Parkinson's disease. AB - In Parkinson's disease (PD) both speech production and self-monitoring of voiced speech are altered. METHODS: In our previous study we used functional magnetic resonance imaging (fMRI) to examine which brain areas are involved in overt reading in nine female PD patients (mean age 66.0 +/- 11.6 years) compared with eight age-matched healthy female controls (mean age 62.2 years +/- 12.3). Here we performed the post-hoc seed-based functional connectivity analysis of our data to assess the functional connectivity between the periaqueductal gray matter (PAG; i.e. the core subcortical structure involved in human vocalization) and other brain regions in the same groups of PD patients and controls. RESULTS: In PD patients as compared with controls we observed increased connectivity between PAG and basal ganglia, posterior superior temporal gyrus, supramarginal and fusiform gyri and inferior parietal lobule on the right side. In the PD group, the connectivity strength in the right putamen and the right sypramarginal gyrus was correlated with variability of pitch while the connectivity strength in the right posterior superior temporal gyrus and in the right inferior parietal lobule was correlated with speech loudness. CONCLUSION: We observed functional reorganization in PD patients as compared with controls in both the motor basal ganglia-thalamo-cortical circuitry and cortical areas known to be engaged in auditory and somatosensory feedback control of voiced speech. These changes were hemisphere-specific and might either reflect effects of dopaminergic treatment or at least partially successful compensatory mechanisms involved in early-stage PD. PMID- 22078746 TI - Control of social monogamy through aggression in a hermaphroditic shrimp. AB - INTRODUCTION: Sex allocation theory predicts that in small mating groups simultaneous hermaphroditism is the optimal form of gender expression. Under these conditions, male allocation is predicted to be very low and overall per capita reproductive output maximal. This is particularly true for individuals that live in pairs, but monogamy is highly susceptible to cheating by both partners. However, certain conditions favour social monogamy in hermaphrodites. This study addresses the influence of group size on group stability and moulting cycles in singles, pairs, triplets and quartets of the socially monogamous shrimp Lysmata amboinensis, a protandric simultaneous hermaphrodite. RESULTS: The effect of group size was very strong: Exactly one individual in each triplet and exactly two individuals in each quartet were killed in aggressive interactions, resulting in group sizes of two individuals. All killed individuals had just moulted. No mortality occurred in single and pair treatments. The number of moults in the surviving shrimp increased significantly after changing from triplets and quartets to pairs. CONCLUSION: Social monogamy in L. amboinensis is reinforced by aggressive expulsion of supernumerous individuals. We suggest that the high risk of mortality in triplets and quartets results in suppression of moulting in groups larger than two individuals and that the feeding ecology of L. amboinensis favours social monogamy. PMID- 22078748 TI - Anthelmintic resistance in non-strongylid parasites of horses. AB - Since 2002, selected populations of Parascaris equorum in several countries have been reported to survive treatment with macrocyclic lactone (M/L) anthelmintics. Clinical treatment failures are characterized by negligible fecal egg count reduction, but M/L resistance has been confirmed in ascarids by controlled efficacy testing. Resistance was selected by current parasite control practices for foals, which often include exclusive and excessively frequent use of M/L dewormers, thereby minimizing refugia within the host and in the environment. Chemical control of M/L-resistant isolates can be accomplished with pyrimidine and/or benzimidazole anthelmintics, but a few M/L-resistant populations have recently exhibited resistance to pyrantel pamoate as well. Some specimens of Oxyuris equi regularly survive treatment with macrocyclic lactones, but it is uncertain whether this constitutes resistance or merely confirms the incomplete oxyuricidal efficacy of virtually all broad spectrum equine anthelmintics. Variations in other biological parameters of Oxyuris and Parascaris, specifically atypical infection of older hosts and shorter prepatent periods, have been reported anecdotally. These changes may represent genetic modifications that have evolved in parallel with resistance as a result of anthelmintic selection pressure. PMID- 22078749 TI - Screening for uterine tumours. AB - The most prevalent uterine tumours are leiomyomas, which are benign and have a prevalence of about 50% at menopause. The incidence of endometrial cancer and uterine sarcomas is about 25 per 100,000 and 0.7 per 100,000, respectively. Reported risk factors for endometrial cancer are advanced age, unopposed oestrogen stimulation, late menopause, obesity, diabetes mellitus, nulliparity, feminising ovarian tumours, polycystic ovarian syndrome, tamoxifen and belonging to a hereditary non-polyposis colorectal cancer family. Unopposed oestrogen stimulation and tamoxifen have also been confirmed to induce uterine sarcomas. Cervical cytology, endometrial sampling and ultrasound have been proposed in the early diagnosis of endometrial cancer. No pathognomonic ultrasound, magnetic resonance imaging or computed tomography features are able to differentiate between a leiomyoma and a uterine sarcoma, and reliable serum markers for sarcomas are lacking. To date, mass screening for uterine malignancies is not feasible or effective. PMID- 22078747 TI - Modulation of oxidative stress and mitochondrial function by the ketogenic diet. AB - The ketogenic diet (KD) is a high-fat, low carbohydrate diet that is used as a therapy for intractable epilepsy. However, the mechanism(s) by which the KD achieves neuroprotection and/or seizure control are not yet known. The broad efficacy of the KD in diverse epilepsies coupled with its profound influence on metabolism suggests that mitochondrial functions may be critical in its mechanism(s) of seizure control. Mitochondria subserve important cellular functions that include the production of cellular ATP, control of apoptosis, maintenance of calcium homeostasis and the production and elimination of reactive oxygen species (ROS). This review will focus on recent literature reporting the regulation of mitochondrial functions and redox signaling by the KD. The review highlights a potential mechanism of the KD involving the production of low levels of redox signaling molecules such as H(2)O(2) and electrophiles e.g. 4 hydroxynonenal (4-HNE), which in turn activate adaptive pathways such as the protective transcription factor, NF E2-related factor 2 (Nrf2). This can ultimately result in increased production of antioxidants (e.g. GSH) and detoxification enzymes which may be critical in mediating the protective effects of the KD. PMID- 22078751 TI - In vitro evaluation of antibacterial activity of Asparagopsis taxiformis from the Straits of Messina against pathogens relevant in aquaculture. AB - Ethanol extracts of Asparagopsis taxiformis collected from the Straits of Messina (Italy) were screened for antibacterial activity against pathogenic shellfish and fish bacteria previously isolated from local marine and brackish environments. Genetic labelling by DNA barcoding allowed us to identify the algal population as a biogeographical strain conspecific to A. taxiformis. The extract obtained in May showed the broadest antibacterial activity against all tested pathogenic bacteria, especially against Vibrio alginolyticus, Vibrio vulnificus and Aeromonas salmonicida subsp. salmonicida. Moderate activity was observed against Photobacterium damselae subsp. damselae and Photobacterium damselae subsp. piscicida, Salmonella sp., Vibrio cholerae, Vibrio harveyi and Vibrio parahaemolyticus. The absence of cytotoxic effects of active algal extracts was verified using trypan blue exclusion test on cells of digestive glands of Mytilus galloprovincialis. The results indicated that ethanol extracts of A. taxiformis could represent a source of antibacterial substances with potential use in aquaculture. PMID- 22078750 TI - Mechanisms of B cell autoimmunity in SLE. AB - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyperreactivity. The underlying causes of the diffuse B-cell over-reactivity are unclear, but potential candidates include (a) intrinsic hyper-reactivity leading to polyclonal B-cell activation with disturbed activation thresholds and ineffective negative selection; (b) lack of immunoregulatory functions; (c) secondary effects of an overactive inflammatory environment, such as overactive germinal center and ectopic follicular activity; and/or (d) disturbed cytokine production by non-B immune cells. These mechanisms are not mutually exclusive and may operate to varying extents and at varying times in SLE. Phenotypic and molecular studies as well as the results of recent clinical trials have begun to provide new insights to address these possibilities. Of importance, new information has made it possible to distinguish between the contribution played by abnormalities in central checkpoints that could lead to a pre-immune repertoire enriched in autoreactive B cells, on the one hand, and the possibility that autoimmunity arises in the periphery from somatic hypermutation and abnormal selection during T cell-dependent B-cell responses on the other. There is an intriguing possibility that apoptotic material bound to the surface of follicular dendritic cells positively selects autoreactive B cells that arise from non-autoreactive B-cell precursors as a result of somatic hypermutation and thereby promotes the peripheral emergence of autoimmunity. PMID- 22078752 TI - Reproductive morbidity among Iranian women; issues often inappropriately addressed in health seeking behaviors. AB - BACKGROUND: Reproductive morbidity has a huge impact on the health and quality of life of women. We aimed to determine the prevalence of reproductive morbidities and the health seeking behavior of a nationally representative sample of Iranian urban women. METHODS: A sample of 1252 women, aged 18-45 years, was selected using the multi stage, stratified probability sampling procedure. Data were collected through interviews and physical, gynecological and ultrasonographic examinations. RESULTS: Reproductive tract infection (RTIs), pelvic organ prolapse (POP) and menstrual dysfunction were the three main groups of morbidities with a prevalence of 37.6%, 41.4% and 30.1%., respectively. Our study demonstrated that 35.1, 34.5 and 9.6 percent of women experienced one, two or these reproductive organ disorders mentioned, respectively, while 20.6 percent of participants had none of these disorders. Findings also showed that the majority of women who suffered from reproductive morbidities (on average two out of three) had not sought appropriate care for these except for infertility. CONCLUSIONS: Reproductive health morbidities impose a large burden among Iranian women and have negative impact on their reproductive health and wellbeing. PMID- 22078753 TI - Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus. AB - Our aims were to compare the systemic effects of insulin on lipoprotein lipase (LPL) in tissues from subjects with different degrees of insulin sensitivity. The effects of insulin on LPL during a 4-hour hyperinsulinemic, euglycemic clamp were studied in skeletal muscle, adipose tissue, and postheparin plasma from young healthy subjects (YS), older subjects with type 2 diabetes mellitus (DS), and older control subjects (CS). In addition, we studied the effects of insulin on the expression of 2 recently recognized candidate genes for control of LPL activity: angiopoietin-like protein 4 (ANGPTL4) and glycosylphosphatidylinositol anchored high-density lipoprotein binding protein 1. As an effect of insulin, LPL activity decreased by 20% to 25% in postheparin plasma and increased by 20% to 30% in adipose tissue in all groups. In YS, the levels of ANGPTL4 messenger RNA in adipose tissue decreased 3-fold during the clamp. In contrast, there was no significant change in DS or CS. Regression analysis showed that the ability of insulin to reduce the expression of ANGPTL4 was positively correlated with M values and inversely correlated with factors linked to the metabolic syndrome. Expression of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 tended to be higher in YS than in DS or CS, but the expression was not affected by insulin in any of the groups. Our data imply that the insulin mediated regulation of LPL is not directly linked to the control of glucose turnover by insulin or to ANGPTL4 expression in adipose tissue or plasma. Interestingly, the response of ANGPTL4 expression in adipose tissue to insulin was severely blunted in both DS and CS. PMID- 22078754 TI - One day of motor training with amphetamine impairs motor recovery following spinal cord injury. AB - It has previously been reported that a single dose of amphetamine paired with training on a beam walking task can enhance locomotor recovery following brain injury (Feeney et al., 1982). Here, we investigated whether this same drug/training regimen could enhance functional recovery following either thoracic (T9) or cervical (C5) spinal cord injury. Different groups of female Sprague Dawley rats were trained on a beam walking task, and in a straight alley for assessment of hindlimb locomotor recovery using the BBB locomotor scale. For rats that received C5 hemisections, forelimb grip strength was assessed using a grip strength meter. Three separate experiments assessed the consequences of training rats on the beam walking task 24 h following a thoracic lateral hemisection with administration of either amphetamine or saline. Beginning 1 h following drug administration, rats either received additional testing/retraining on the beam hourly for 6 h, or they were returned to their home cages without further testing/retraining. Rats with thoracic spinal cord injuries that received amphetamine in conjunction with testing/retraining on the beam at 1 day post injury (DPI) exhibited significantly impaired recovery on the beam walking task and BBB. Rats with cervical spinal cord injuries that received training with amphetamine also exhibited significant impairments in beam walking and locomotion, as well as impairments in gripping and reaching abilities. Even when administered at 14 DPI, the drug/training regimen significantly impaired reaching ability in cervical spinal cord injured rats. Impairments were not seen in rats that received amphetamine without training. Histological analyses revealed that rats that received training with amphetamine had significantly larger lesions than saline controls. These data indicate that an amphetamine/training regimen that improves recovery after cortical injury has the opposite effect of impairing recovery following spinal cord injury because early training with amphetamine increases lesion severity. PMID- 22078755 TI - Response to the report, "A re-assessment of a combinatorial treatment involving Schwann cell transplants and elevation of cyclic AMP on recovery of motor function following thoracic spinal cord injury in rats" by Sharp et al. (this volume). PMID- 22078756 TI - Replication and reproducibility in spinal cord injury research. AB - This special issue of Experimental Neurology compiles a series of papers that either explicitly replicate published studies or retest phenomena reported in previous publications. The explicit replications were carried out as part of the "Facilities of Research Excellence-Spinal Cord Injury" (FORE-SCI) program launched by the National Institute of Neurological Disorders and Stroke (NINDS) in 2003. Here, we review the FORE-SCI replication experiments published prior to those in this special issue. We then discuss emerging issues regarding replication and reproducibility in spinal cord injury research, especially in terms of potential translation to clinical trials. PMID- 22078757 TI - Anti-CD11d monoclonal antibody treatment for rat spinal cord compression injury. AB - This paper by Hurtado et al. examined responses of spinal cord-injured rats to treatment with a monoclonal antibody to the CD11d integrin, as a replication study of the paper by Gris et al. published in J. Neuroscience, 2004. The Hurtado et al. study addressed a portion of our investigation and obtained similar findings in the experiments that closely replicated ours in methodology and design, specifically the open field locomotor study. The high variability in their study of mechanical allodynia probably precluded detection of effects of the anti-CD11d treatment on this form of neuropathic pain. The lesion assessments were greatly different from those done in the Gris et al. study, and may not have been ideal for the extent of injury produced in this model, but did reveal a trend toward myelin preservation. The positive aspects of the study by Hurtado et al. encourage us to investigate this novel treatment further, in different animals and in different models of spinal cord injury. PMID- 22078758 TI - Oncomodulin affords limited regeneration to injured sensory axons in vitro and in vivo. AB - Oncomodulin, an ~12 kDa Ca(2+)-binding protein secreted from activated macrophages, has been shown to promote axonal regeneration from retinal ganglion cells (RGCs) following optic nerve injury. However, to date, the axonal growth promoting capacity of oncomodulin in other models of 'regenerative failure' has not been evaluated. We assessed the capability of preconditioning treatment with oncomodulin to promote sensory axonal regeneration in an in vitro spot model of regenerative failure, and across the dorsal root zone (DREZ) after root crush injury. Neither the direct exposure of adult rat DRGs to oncomodulin, nor preconditioning of DRGs by intraganglionic injection of oncomodulin, stimulated axonal outgrowth in the in vitro proteoglycan spot gradient assay. However, direct exposure of unconditioned DRGs to both oncomodulin and db-cAMP in vitro, as well as preconditioning of DRGs with the combined treatment in vivo, resulted in significant, albeit modest, neurite extension across the inhibitory proteoglycan barrier. We next quantified axon regeneration through the C8 DREZ in adult rats after oncomodulin and/or db-cAMP preconditioning and chondroitinase (ChABC) injection into the DREZ immediately following a root crush injury. Axonal regeneration across the DREZ was not observed in control animals, or after injection of ChABC-alone. Treatment with oncomodulin- or db-cAMP-alone resulted in extremely sparse regeneration. However, significant, but meager, sensory axon regeneration across the DREZ was observed using the oncomodulin/ db-cAMP combination (p<0.001), supporting findings from previous studies suggesting that cAMP is necessary for the growth-promoting effects of oncomodulin. Although our results support a role for oncomodulin in macrophage-induced axonal regeneration, the effects of oncomodulin/db-cAMP on sensory regeneration were extremely limited in comparison to previous studies in the same injury model using zymosan. PMID- 22078759 TI - When replication teaches more than the original experiment--the saga of the unknown unknown. AB - We recently published a description of the molecular mechanism involved in "progressive hemorrhagic necrosis", a pathological process that evolves during several hours after spinal cord injury, that is attributable to progressive capillary fragmentation, and that is due to upregulation and activation of SUR1 regulated channels in microvascular endothelium. In this commentary, we reflect on the independent replication of our original experiment by Dr. Phillip Popovich and colleagues, and how their initial attempt at replication led to the unexpected finding that anisotropy of spinal cord tissues strongly influences the patterns of both primary and secondary hemorrhage that are observed after impact injury to the spinal cord. PMID- 22078761 TI - A re-assessment of the effects of treatment with an epidermal growth factor receptor (EGFR) inhibitor on recovery of bladder and locomotor function following thoracic spinal cord injury in rats. AB - This study was undertaken as part of the NIH "Facilities of Research Excellence Spinal Cord Injury" project to support independent replication of published studies. Here, we repeat an experiment in which rats that received an inhibitor of the epidermal growth factor receptor (EGFR) exhibited greater sparing/recovery of bladder and motor function and enhanced sparing at the lesion site after contusion injuries at the thoracic level. Young adult female Sprague-Dawley rats received moderate contusions with the NYU impactor (10 g from 12.5 mm, 2 mm rod diameter), and then were implanted with catheters attached to osmotic minipumps for intra-spinal delivery of either PD168393 dissolved in 5% DMSO and HBSS or vehicle alone. Motor function was assessed with the Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB) and with a grid walk task. Bladder function was assessed by measuring the amount of urine retained in the bladder. Tactile sensitivity was assessed using von Frey hairs and heat and cold sensitivity were assessed by testing hindlimb sensitivity to ethylchloride spray and a hotplate respectively. Rats that received PD168393 were more impaired on motor assessments and also showed greater bladder impairment (larger amounts of retained urine) than rats that received vehicle. These results thus fail to confirm previous studies reporting enhanced recovery following treatment with PD168393. PMID- 22078760 TI - A reassessment of P2X7 receptor inhibition as a neuroprotective strategy in rat models of contusion injury. AB - These experiments were completed as part of an NIH "Facilities of Research Excellence in Spinal Cord Injury" contract to support independent replication of published studies that could be considered for eventual clinical testing. Recent studies have reported that selective inhibition of the P2X7 receptor improves both the functional and histopathological consequences of a contusive spinal cord injury (SCI) in rats. We repeated two published studies reporting the beneficial effects of pyridoxal-5'-phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) or Brilliant blue G (BBG) treatment after SCI (Wang et al., 2004 and Peng et al., 2009). Mild thoracic SCI was first produced in Experiment 1 by means of the MASCIS impactor at T10 (height 6.25 mm, weight 10 g) followed by intraspinal administration of a P2X7 antagonist (2 MUl/10 mM) after injury. Treatment with PPADS or another highly selective P2X7R antagonist Brilliant Blue G (BBG) (2 MUl/02 mM) did not improve locomotive (BBB rating scale) over a 7 week period compared to vehicle treated rats. Also, secondary histopathological changes in terms of overall lesion and cavity volume were not significantly different between the PPADS, BBG, and vehicle treated animals. In the second experiment, the systemic administration of BBG (10 or 50 mg/kg, iv) 15 min, 24 and 72 h after moderate (12.5 mm) SCI failed to significantly improve motor recovery or histopathological outcome over the 6 week observational period. Although we cannot conclude that there will be no long-term beneficial effects in other spinal cord injury models using selective P2X7 receptor antagonists at different doses or treatment durations, we caution researchers that this potentially exciting therapy requires further preclinical investigations before the implementation of clinical trials targeting severe SCI patients. PMID- 22078762 TI - [Glycemic control in non-critical hospitalized patients]. AB - OBJECTIVES: To assess in hospitalized patients the prevalence of hyperglycemia, degree of glycemic control, rate of hypoglycemia, and treatment used. PATIENTS AND METHODS: A prospective, observational study. RESULTS: Hyperglycemia was found in 185 (26.7%) of 691 patients, of whom 85% had been diagnosed with diabetes and 15% had no diabetes. Preprandial mean blood glucose was 169 mg/dL (95% CI 160 177). Control goals were achieved by 34.5% of patients (blood glucose <=140 mg/dL). In 121 patients only sliding-scale regular insulin was used, while 64 patients received both basal and regular insulin. The mean daily insulin dose used was 19.5 units. Oral antidiabetics were given to 11.4% of patients. Thirteen patients (7%) experienced hypoglycemia (< 70 mg/dL), none of them severe. CONCLUSIONS: Glycemic control is not adequate in hospitalized patients, probably because of overuse of sliding scales and the low insulin doses used. PMID- 22078763 TI - [Postprandial lipemia induces endothelial dysfunction and higher insulin resistance in healthy subjects]. AB - OBJECTIVE: To assess the effect of postprandial lipemia on endothelial function, insulin resistance, and lipid profile in healthy subjects. PATIENTS AND METHODS: A prospective', interventional study in 14 healthy young men aged 18-25 years who were given a high-fat meal. Endothelial function was measured using flow-mediated dilation (FMD) in the brachial artery, flow velocity, mean arterial pressure and serum nitrite/nitrate levels (NO(2)/NO(3)). Glucose, insulin, total cholesterol, and triglyceride levels were also tested. Insulin resistance was determined by calculating the HOMA-IR index (Homeostatic Model Assessment-Insulin Resistance). RESULTS: Baseline FMD was 5.9 +/- 1.1%. Postprandial lipemia reduced endothelial function by approximately 50% in the first (3.3 +/- 0.5%, p=0.03) and second (3.3 +/- 0.4%, p=0.04) moment respectively. This finding was associated to an increased flow rate in the brachial artery and lower NO(2)/NO(3) levels (p<0.05). Higher cholesterol and triglyceride levels were found 1h and 2h postprandial (p<0.05). HOMA-IR was significantly increased 1h and 2h postprandial (p<0.05). CONCLUSIONS: Postprandial lipemia causes changes in circulating lipid profile and induces endothelial dysfunction and higher insulin resistance. PMID- 22078764 TI - Differentiation of human mesenchymal stem cells on niobium-doped fluorapatite glass-ceramics. AB - OBJECTIVE: Our goal was to characterize the response of human mesenchymal stem cells (hMSCs) to a niobium-doped fluorapatite-based glass-ceramic (FAp). METHODS: The glass was prepared by twice melting at 1525 degrees C for 3 h, and cast into cylindrical ingots later sectioned into discs and heat-treated to promote crystallization of fluorapatite submicrometer crystals. Tissue culture polystyrene (TCP) was used as control. The surface of the FAp discs was either left as-heat treated, ground or etched. Initial cell attachment was assessed at 3 h. Proliferation and alkaline phosphatase (ALP) expression data were collected at days 1, 4, and 8. Cell morphology was examined using SEM, at days 2 and 4. Mineralization was evaluated by Alizarin Red staining and SEM. RESULTS: Initial cell attachment on as heat-treated, etched, or ground surfaces was similar to that of the positive control group (p>0.05). The percentage of area covered by living cells increased significantly on as heat-treated, etched, or ground surfaces between days 1 and 8 (p<0.05). There was no significant difference among groups in cell coverage at day 8, compared to TCP control. SEM revealed well spread polygonal cells with numerous filopodia, either attached to the ceramic surface or connected to neighboring cells. ALP expression at day 8 was significantly higher in osteogenic media compared to growth media on both FAp and control. FAp discs stained positively with Alizarin Red and calcium-rich mineralized granules associated with fibrils were observed by SEM at day 35. SIGNIFICANCE: hMSCs displayed excellent attachment, proliferation, and differentiation on niobium-doped FAp glass-ceramic. PMID- 22078765 TI - Molecular docking of gamma-sitosterol with some targets related to diabetes. AB - gamma-sitosterol isolated from Lippia nodiflora was taken as ligand for molecular docking. The molecular targets, glucokinase, Fructose 1, 6- bisphosphatase 1, Human multidrug resistance protein 1 and Cytochromes P450 whose crystallographic structures are available on the PDB database as 1V4S, 2JJK, 3LC4, 2CBZ respectively, were used for the docking analysis using the Autodock tool v 4.2 and ADT v1.5.4 programs. The docking studies of the ligand gamma- sitosterol with four different target proteins showed that this is a good molecule which docks well with various targets related to diabetes mellitus. Hence gamma-sitosterol can be considered for developing into a potent antidiabetic drug. PMID- 22078766 TI - Phylogenetic inference for function-valued traits: speech sound evolution. AB - Phylogenetic models have recently been proposed for data that are best represented as a mathematical function (i.e. function valued). Such methods can be used to model the change over time in function-based descriptions of various data of interest to evolutionary biologists, including the sound of speech. This approach to phylogenetic inference and analysis is challenging, both in terms of modeling the phylogenetics of functions and in engaging with previously existing evidence for character-state change. Nevertheless, it is both a real and exciting prospect. Our approach could provide those interested in investigating a greater range of evolutionary processes with the ability to use statistical hypothesis testing procedures and to create estimates of the states of function-valued characteristics (e.g. speech sounds) at earlier historical times. PMID- 22078767 TI - [Anogenital granulomatosis]. PMID- 22078768 TI - [Lichen sclerosus and squamous cell carcinoma]. AB - Lichen sclerosus is a chronic inflammatory disease that can progress to malignancy. The literature indicates an association with anogenital squamous cell carcinoma and verrucous carcinoma. Two pathogenic pathways, differentiated vulvar and penile intraepithelial neoplasias, which have recently been described in relation to squamous cell carcinoma, are both highly associated with genital lichen sclerosus independently of human papilloma virus (HPV) infection. Furthermore, tumor-promoting molecular changes unrelated to HPV infection have been demonstrated and may explain the malignant potential of lichen sclerosus. The possible relationship between HPV and genital lichen sclerosus currently remains open to discussion, and the prognostic importance of the overlapping of these 2 diseases is still unclear. This review considers the relationship between lichen sclerosus and squamous cell and verrucous carcinomas, the possible oncogenic mechanisms involved, and their possible association with HPV infection. PMID- 22078769 TI - Review our reviews: JNEB 2011. PMID- 22078770 TI - The new Society for Nutrition Education... "and Behavior". PMID- 22078771 TI - Food perceptions and concerns of aboriginal women coping with gestational diabetes in Winnipeg, Manitoba. AB - OBJECTIVE: To describe how Aboriginal women in an urban setting perceive dietary treatment recommendations associated with gestational diabetes mellitus (GDM). DESIGN: Semi-structured explanatory model interviews explored Aboriginal women's illness experiences with GDM. SETTING AND PARTICIPANTS: Twenty-nine self-declared Aboriginal women who had received a diagnosis of GDM within the last 5 years in Winnipeg, Manitoba. MAIN OUTCOME MEASURES: Factors influencing Aboriginal women's prenatal food perceptions with GDM. ANALYSIS: Thematic analysis was used through coding linkages and matrix queries to assist in identifying and categorizing patterns or relationships. RESULTS: Participants associated fear, anxiety, and frustration with GDM. Emotional reactions appeared alongside negative relationships with food and other prescribed lifestyle treatments. Collectively, these results suggested that the experience of living with GDM can be overwhelming, as suggested by some of the complex factors influencing women's perceptions and reported behaviors. Discussions indicated many felt socially isolated and had a poor self-image and sense of failure resulting from ineffective GDM management practices. CONCLUSIONS AND IMPLICATIONS: Future efforts should focus on self-efficacy and security in Aboriginal women's own interpretation of GDM, providing them with the understanding that there is potential for prevention and change. PMID- 22078772 TI - Accessing the food systems in urban and rural Minnesotan communities. AB - OBJECTIVE: Explore how urban and rural Minnesotans access the food system and to investigate whether community infrastructure supports a healthful food system. DESIGN: Eight (4 urban and 4 rural) focus groups were conducted. SETTING AND PARTICIPANTS: Eight counties with urban influence codes of 1, 2, 4, 5, 8, and 10. Fifty-nine (urban, n = 27; rural, n = 32) adults. The sample was of mixed race and had a range of incomes. Almost half of the sample was obese. MAIN OUTCOME MEASURE: Food systems access and the role of community infrastructure, civic engagement, and reciprocal relationships in food provisioning in counties with different urban influence codes. ANALYSES: Themes and subthemes were identified through emerging concepts. RESULTS: Food access varied based on rurality and community infrastructure. Three themes emerged: community infrastructure around the conventional food system and food provisioning, alternative food resources, and perceptions of the effect food and of the influence diet and exercise have on health. CONCLUSIONS AND IMPLICATIONS: Civic engagement and community infrastructure affected food access. Rural residents rely more on retail grocery stores, gardening, hunting, and informal food exchange systems, whereas urban residents rely more on the retail grocery stores and food safety net systems. Hunting and gardening may contribute valuable nutrients to the diet. PMID- 22078773 TI - Qualitative investigation of the Cooking with Kids program: focus group interviews with fourth-grade students, teachers, and food educators. AB - OBJECTIVE: Focus group (FG) interviews with students and adults were used to obtain a rich understanding of the Cooking with Kids classroom experience from the child and adult participant perspectives. METHODS: FG topics included students' cooking experiences at school and home and perceptions of Cooking with Kids. Verified transcripts of recorded interviews were entered into NVivo, coded for themes, and confirmed through intercoder reliability. RESULTS: Twenty-two FGs were conducted with fourth-grade students (n = 178), 3 FG with teachers (n = 17), and 1 FG with 5 Cooking with Kids food educators. Students in cooking interventions described positive experiences with curriculum integration into academic subjects and were more likely to consider classmates friends. CONCLUSIONS AND IMPLICATIONS: FG revealed student perspectives to strengthen content and implementation of experiential foods programs. This study provides an example of how qualitative methods can add "student voice" to evaluation of school-based programs. PMID- 22078774 TI - Variables of the Theory of Planned Behavior are associated with family meal frequency among adolescents. AB - OBJECTIVE: To examine associations between Theory of Planned Behavior variables and the family meal frequency. METHODS: Fifth-through seventh-grade students (n = 236) completed a self-administered questionnaire in their classrooms. The relationships between Theory of Planned Behavior variables (intention, attitudes, subjective norms, and perceived behavioral control) and family meal frequency were examined with Spearman correlations and multiple logistic regression analysis. RESULTS: Positive intention, positive subjective norm of family eating together, and lower perceived difficulty of making time increased the odds of adolescents having family dinners at least 5 d/wk compared with adolescents having family dinners 2 days or fewer per week. Positive intention and lower perceived difficulty for making time increased odds of having family breakfasts at least 5 d/wk. CONCLUSIONS AND IMPLICATIONS: To increase family meal frequency, nutrition educators are encouraged to focus on increasing intention, creating positive norms about the family meal, and reducing perceived barriers caused by time conflicts. PMID- 22078776 TI - Recruiting EFNEP participants: process and materials. PMID- 22078775 TI - Identifying and clarifying values and reason statements that promote effective food parenting practices, using intensive interviews. AB - OBJECTIVE: Generate and test parents' understanding of values and associated reason statements to encourage effective food parenting practices. METHODS: This study was cross-sectional. Sixteen parents from different ethnic groups (African American, white, and Hispanic) living with their 3- to 5-year-old child were recruited. Interested parents were directed to a Web site, where they provided screening information and informed consent. Two types of telephone interviews were used: semistructured intensive interviews and cognitive interviews. RESULTS: The most common core values identified in the semistructured interview were religion/spirituality, family, and health, which appeared invariant across parent ethnicity. Parent responses to cognitive interviews enabled rephrasing of statements that were not well understood, the list of values was increased, and reason statements were added to cover the spectrum cited by parents. CONCLUSIONS AND IMPLICATIONS: Values and reason statements will be used to tailor intrinsic motivational messages for effective food parenting practices. PMID- 22078777 TI - Recruiting EFNEP agency partners: process and materials. PMID- 22078778 TI - Survival and differentiation of transplanted neural stem cells derived from human induced pluripotent stem cells in a rat stroke model. AB - BACKGROUND: Although administration of various stem cells has shown promise in stroke models, neural stem cells (NSCs) derived from human induced pluripotent stem cells (iPSCs) have advantages over other cell types. We studied whether these cells could survive, differentiate, and improve stroke recovery in an ischemic stroke model. METHODS: Human iPSCs were induced in vitro to an early NSC stage. One week after focal cerebral ischemia, 20 rats received cells or vehicle by intracerebral injection. Graft cell fate, infarct volume, and behavioral deficits were assessed. RESULTS: Graft cells were found in 8 of the transplanted rats (80%), with estimated mean graft cell numbers nearly double the amount transplanted 1 month later. Graft cells also expressed markers of NSCs in 5 rats (63%), neurons in all 8 rats (100%), rare astrocytes in 4 rats (50%), and signs of proliferation in 4 rats (50%), but no tumor formation was observed. Stroke volume and behavioral recovery were similar between the groups. CONCLUSIONS: To our knowledge, this is the first report of transplantation of NSCs derived from human iPSCs in a stroke model. Human iPSC-derived NSCs survived in the postischemic rat brain and appeared to differentiate, primarily into neurons. This cell transplantation approach for stroke appears to be feasible, but further optimization is needed. PMID- 22078779 TI - Effects of constraint-induced movement therapy on spasticity in patients with hemiparesis after stroke. AB - BACKGROUND: We sought to examine the effects of constraint-induced movement therapy on spasticity in patients with hemiparesis after stroke in 10 patients with chronic hemiparesis in their upper extremities. METHODS: Patients underwent a modified version of constraint-induced movement therapy (5 hours daily for 10 weekdays over 2 consecutive weeks). Motor function was assessed by the Fugl-Meyer Assessment, Wolf Motor Function Test, and the Motor Activity Log. Spasticity was assessed by the modified Ashworth scale and electromyography (F frequency, mean F/M ratio). These assessments were obtained immediately before and after the 2 week intervention. Wilcoxon rank sum tests were performed on these data (P < .05). RESULTS: Constraint-induced movement therapy significantly improved hand and arm function as indicated by the Fugl-Meyer Assessment, Wolf Motor Function Test, and the Motor Activity Log scores. Constraint-induced movement therapy also reduced spasticity as assessed by the modified Ashworth scale, F frequency, and mean F/M ratio. CONCLUSIONS: Comparable to motor function, constraint-induced movement therapy effectively reduces spasticity as confirmed by electromyography. PMID- 22078780 TI - Risk factors among stroke subtypes in Brazil. AB - Stroke is a leading cause of mortality and disability in Brazil. Among the risk factors for cerebrovascular disease, some have more influence than others in certain stroke subtypes. Little data are available in the literature on the prevalence of stroke subtypes in Latin America. We analyzed data from 688 patients with acute ischemic stroke (52.3% women; mean age, 65.7 years) who were enrolled in a stroke data bank. Standardized data assessment and stroke subtype classification were used. The most common stroke subtype was large-artery atherosclerosis (n = 223; 32.4%), followed by cardioembolism (n = 195; 28.3%), and microangiopathy (n = 127; 18.5%). Stroke risk factors differ among stroke subtypes. The population of South America is ethnically diverse, and few previous studies have describe the distribution of risk factors among stroke subtypes in this population. In this study, the most important risk factors were hypertension and dyslipidemia. PMID- 22078781 TI - Are racial disparities in stroke care still prevalent in certified stroke centers? AB - Racial differences in stroke risk and risk factor prevalence are well established. The present study explored racial differences in the delivery of care to patients with acute stroke between Joint Commission (JC)-certified hospitals and noncertified hospitals. A retrospective chart review was conducted in patients sustaining ischemic stroke admitted to 5 JC-certified centers and 5 noncertified hospitals. Demographic data, risk factors, utilization of acute stroke therapies, and compliance with core measures were recorded. Racial disparities were investigated in the entire group as well as for JC-certified and noncertified hospitals separately. A total of 574 patients (25.1% African Americans) were included. African Americans were significantly younger and more likely to have previous stroke, whereas Caucasians were more likely to have coronary disease and atrial fibrillation. There were no racial differences in other risk factors or baseline functions. Median National Institutes of Health Stroke Scale scores were similar in African Americans and Caucasians, as were proportions receiving intravenous tissue plasminogen activator (tPA) therapy (2.1% in African Americans, 3.5% in Caucasians; P = .40) and intervention (4.2% in African Americans, 6.8% in Caucasians; P = .26). Caucasians were more likely to arrive by emergency medical services (65.5% vs 51.5%; P = .004), to be evaluated by a stroke team (19.1% vs 7.7%; P = .001), and to have a documented National Institutes of Health Stroke Scale score (40.2% vs 29.9%; P = .03). African Americans often did not receive intravenous tPA because of a delay in arrival. African Americans performed better on virtually all stroke care variables in JC-certified centers. JC certification reduced disparity in certain variables, including tPA and deep venous thrombosis prophylaxis administration. Important racial disparities exist in the delivery of several acute stroke care variables. Efforts must be focused on eliminating disparities in prehospital delays. Guideline-based care tendered at JC-certified centers might help narrow disparities in acute stroke care delivery. PMID- 22078782 TI - Androgen signaling in decidualizing human endometrial stromal cells enhances resistance to oxidative stress. AB - OBJECTIVE: To investigate the effect of androgens on the expression of genes involved in oxidative stress resistance in decidualized human endometrial stromal cells (HESCs). DESIGN: In vitro experiment. SETTING: University hospital. PATIENT(S): Premenopausal women undergoing hysterectomy for uterine fibroids. INTERVENTION(S): Human endometrial stromal cells isolated from hysterectomy specimens were decidualized with 8-bromo-cyclic adenosine monophosphate (8-br cAMP) and P in the presence or absence of dihydrotestosterone (DHT) at various concentrations. Hydrogen peroxide was used as a source of reactive oxygen species. MAIN OUTCOME MEASURE(S): Prolactin secretion, apoptosis, FOXO1, and the free radical scavengers superoxide dismutase 2 (SOD2) and SOD1 protein expression. RESULT(S): Prolactin production was induced in HESCs in response to 8 br-cAMP and P. Dihydrotestosterone further enhanced the secretion of PRL in cells treated with 8-br-cAMP plus P. The effect of DHT was blocked by the antiandrogen flutamide. Dihydrotestosterone enhanced resistance to oxidative stress-induced apoptosis on decidualized HESCs. Moreover, DHT enhanced FOXO1 expression in parallel with increased SOD2 protein but not with SOD1. CONCLUSION(S): Androgens might play a critical role in the decidualization process at the time of embryo implantation and trophoblast invasion by promoting resistance to oxidative stress. PMID- 22078784 TI - Ovarian response to stimulation for fertility preservation in women with malignant disease: a systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the current available data regarding ovarian performance of patients diagnosed with malignant disease undergoing controlled ovarian hyperstimulation (COH) for fertility preservation, before radio/chemotherapy, compared with age-matched, healthy patients undergoing COH for in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). DESIGN: Meta-analysis of the data available from a systematic review of the literature. SETTING: Academic centers of infertility and IVF. PATIENT(S): Patients with malignant disease, before radio/chemotherapy, undergoing COH for fertility preservation within comparative studies with healthy, age-matched controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Peak estradiol levels on day of human chorionic gonadotropin administration, number of oocytes retrieved, fertilization rate, incidence of low ovarian response, and cycle cancellation. RESULT(S): Only seven retrospective, case-controlled studies were found to match our objective. Overall, the results of the meta-analysis indicate that the number of retrieved oocytes rate was statistically significantly lower compared with age-matched healthy IVF patients. The incidence of poor ovarian performance and risk of cycle cancellation as well as the calculated number of two pronuclei zygotes achieved among patients with cancer were comparable with their age-matched controls. CONCLUSION(S): Women with malignant disease should expect a lower number of oocytes retrieved after COH for fertility preservation, compared with healthy, age-matched patients. Presently, there is paucity of evidence to assess the effect of a specific malignant disease on ovarian response to COH before IVF for fertility preservation. Multicentric studies should be conducted to resolve these important issues. PMID- 22078783 TI - Food intake and social habits in male patients and its relationship to intracytoplasmic sperm injection outcomes. AB - OBJECTIVE: To investigate the influence of the male partner's lifestyle, including eating and social habits, on semen quality and intracytoplasmic sperm injection (ICSI) success. DESIGN: Observational study. SETTING: Private fertility clinic. PATIENT(S): Two hundred fifty male patients undergoing ICSI cycles. INTERVENTION(S): We recorded dietary and social habits using a food frequency questionnaire adapted to meet specific study objectives. Evaluation of semen parameters and ICSI outcomes were performed. MAIN OUTCOME MEASURE(S): Frequency of intake of food items and social habits were registered on a scale with five categories ranging from no consumption to repeated daily consumption. RESULT(S): The sperm concentration was negatively influenced by body mass index (BMI) and alcohol consumption and was positively influenced by cereal consumption and the number of meals per day. The sperm motility was also negatively influenced by BMI, alcohol consumption, and smoking habit, whereas it was positively influenced by the consumption of fruits and cereals. The consumption of alcohol had a negative influence on the fertilization rate. The consumption of red meat as well as being on a weight loss diet had a negative impact on the implantation rate. In addition, the consumption of red meat and being on a weight loss diet had an effect on the pregnancy chance. CONCLUSION(S): Couples seeking assisted reproduction treatments must be advised about the drastic effect of both the male and female lifestyle on treatment success. PMID- 22078785 TI - A novel method based on curvature analysis for estimating the dietary vitamin K requirement in adolescents. AB - BACKGROUND & AIMS: Few studies have investigated the association between vitamin K status and bone health in adolescents. We established a novel method for estimating the vitamin K status in adolescents by curvature analysis using the serum concentrations of undercarboxylated osteocalcin (ucOC)-a sensitive biomarker of vitamin K status in the bone. We also compared the vitamin K concentrations required for good bone health and for normal blood coagulation. METHOD: We enrolled 1183 healthy adolescents. For the curvature analysis, we used a logarithmic regression equation obtained from vitamin K intake and serum ucOC or plasma abnormal prothrombin (PIVKA-II) concentrations (marker for blood coagulation). The cut-off point was determined to be the vitamin K intake that showed the highest curvature. RESULTS: In adolescents, the serum ucOC concentration was negatively correlated with vitamin K intake. In the curvature analysis, requirement of vitamin K intake for good bone health and normal blood coagulation were 155-188 MUg/d and 62-54 MUg/d [1 MUg/(kg d)], respectively; the latter result was consistent with that of a previous report. CONCLUSION: Our novel method is useful for estimating the vitamin K status; moreover, this method showed that bone metabolism requires more vitamin K than blood coagulation. PMID- 22078788 TI - A new paradigm for surgical procedural training. PMID- 22078789 TI - Latent myofascial trigger points are associated with an increased antagonistic muscle activity during agonist muscle contraction. AB - The aim of this study was to evaluate motor unit activity from a latent myofascial trigger point (MTP) in an antagonist muscle during isometric agonist muscle contraction. Intramuscular activity was recorded with an intramuscular electromyographic (EMG) needle inserted into a latent MTP or a non-MTP in the posterior deltoid muscle at rest and during isometric shoulder flexion performed at 25% of maximum voluntary contraction in 14 healthy subjects. Surface EMGs were recorded from the anterior and posterior deltoid muscles. Maximal pain intensity and referred pain induced by EMG needle insertion were recorded on a visual analogue scale. The results showed that higher local pain was observed following needle insertion into latent MTPs (4.64 +/- .48 cm) than non-MTPs (2.35 +/- .43 cm, P < .005). Referred pain was reported in 6/14 subjects following needle insertion into latent MTPs, but none into the non-MTPs. The intramuscular EMG activity, but not surface EMG activity, in the antagonist muscle was significantly higher at rest and during shoulder flexion at latent MTPs than non MTPs (P < .05). The current study provides the first evidence that increased motor unit excitability is associated with reduced antagonist reciprocal inhibition. PERSPECTIVE: This study shows that MTPs are associated with reduced efficiency of reciprocal linhibition, which may contribute to the delayed and incomplete muscle relaxation following exercise, disordered fine movement control, and unbalanced muscle activation. Elimination of latent MTPs and/or prevention of latent MTPs from becoming active may improve motor functions. PMID- 22078790 TI - Swearing as a response to pain-effect of daily swearing frequency. AB - Previously we showed that swearing produces a pain lessening (hypoalgesic) effect for many people.(20) This paper assesses whether habituation to swearing occurs such that people who swear more frequently in daily life show a lesser pain tolerance effect of swearing, compared with people who swear less frequently. Pain outcomes were assessed in participants asked to repeat a swear word versus a nonswear word. Additionally, sex differences and the roles of pain catastrophizing, fear of pain, and daily swearing frequency were explored. Swearing increased pain tolerance and heart rate compared with not swearing. Moreover, the higher the daily swearing frequency, the less was the benefit for pain tolerance when swearing, compared with when not swearing. This paper shows apparent habituation related to daily swearing frequency, consistent with our theory that the underlying mechanism by which swearing increases pain tolerance is the provocation of an emotional response. PERSPECTIVE: This article presents further evidence that, for many people, swearing (cursing) provides readily available and effective relief from pain. However, overuse of swearing in everyday situations lessens its effectiveness as a short-term intervention to reduce pain. PMID- 22078791 TI - Atypical myocardial delayed enhancement after surgical ventricle restoration. AB - OBJECTIVE: To retrospectively evaluate delayed enhancement after surgical ventricle restoration (SVR). MATERIALS AND METHODS: Thirty patients with post ischemic akinetic dilatation underwent cine and gadobenate dimeglumine-enhanced MRI before and 2-6 months after SVR. End-diastolic volume (EDV) normalized to body surface area (EDV index, EDVI), end-systolic volume index (ESVI), and ejection fraction (EF) of the left ventricle were obtained. Delayed enhancement involving subendocardial myocardium was considered typical (TDE) while enhancement apparently not involving subendocardium in its typical location was considered atypical (ADE). Wilcoxon signed-rank, Mann-Whitney U, and chi2 tests were used. RESULTS: All 30 patients showed TDE prior to surgery but 16 of them (53%) showed ADE after SVR. Before SVR, EDVI (ml/m2) was 171+/-101 in patients with ADE and 127+/-41 in patients with TDE, ESVI (ml/m2) was 130+/-105 and 94+/ 36, EF was 25+/-6% and 24+/-9%, respectively, without significant differences (P>0.347). After SVR, EDVI (ml/m2) was 99+/-24 and 89+/-28 (P=0.275), ESVI (ml/m2) 66+/-24 and 65+/-30, respectively, without significant differences (P>0.275) while EF was 37+/-12% and 29+/-13%, respectively, with a near significant difference (P=0.077). The increase in EF before/after SVR was significant only for patients with ADE (P=0.006). Of 20 patients in whom a patch had been used for SVR, 14 showed ADE and 6 TDE; of 10 patients without patch, 2 and 8, respectively (P=0.010). CONCLUSION: ADE was found in about half of SVR patients and was associated with the use of patch and EF improvement. PMID- 22078792 TI - MRI of the cuboid bone: analysis of changes in diabetic versus non-diabetic patients and their clinical significance. AB - OBJECTIVES: (1) To investigate the association between diabetes and marrow changes in the cuboid; and (2) to evaluate the influence of age, gender, body mass index (BMI) and use of insulin in the occurrence of marrow changes in the cuboid. RESEARCH DESIGN AND METHODS: MR and X-ray foot examinations of 237 patients [94 males, 143 females; mean age, 47.1 years (range 16-93 years)], five of whom underwent bilateral examinations, were reviewed. MR and radiographic studies were analyzed for the presence of marrow edema and fractures in the cuboid. Findings were correlated with demographic data (age, gender) and clinical information (BMI and use of insulin). RESULTS: Two hundred and forty two feet - 69 diabetic and 173 non-diabetic - were retrospectively evaluated. There was a higher prevalence of marrow edema and fractures in the diabetic cuboid (n=31, 45%) compared to non-diabetic cuboid (n=25, 14%, p=0.02). A fracture line was seen in fourteen (20%) diabetic cuboid bones compared to 4 (2%) in non-diabetic cuboid bones (p<0.0001). Eleven (79%) cases of cuboid fractures in the diabetic population were radiographically occult. Multivariate data analysis revealed an adjusted odds ratio of 4.416 (95% CI; 2.307, 8.454) for the relationship between marrow changes (edema and fractures) in the cuboid and diabetes. For each year of age, the odds of changes in the cuboid increased by 2.2% (95% CI; 1.001, 1.044). CONCLUSION: Despite not bearing weight, the cuboid bone is more vulnerable to marrow edema and fractures in diabetic patients compared to non-diabetic patients. Age seems to be an influential factor. PMID- 22078793 TI - Simulation of a MR-PET protocol for staging of head-and-neck cancer including Dixon MR for attenuation correction. AB - PURPOSE: To simulate and optimize a MR protocol for squamous cell cancer of the head and neck (HNSCC) patients for potential future use in an integrated whole body MR-PET scanner. MATERIALS AND METHODS: On a clinical 3T scanner, which is the basis for a recently introduced fully integrated whole-body MR-PET, 20 patients with untreated HNSCC routinely staged with 18F-FDG PET/CT underwent a dedicated MR protocol for the neck. Moreover, a whole-body Dixon MR-sequence was applied, which is used for attenuation correction on a recently introduced hybrid MR-PET scanner. In a subset of patients volume-interpolated-breathhold (VIBE) T1w sequences for lungs and liver were added. Total imaging time was analyzed for both groups. The quality of the delineation of the primary tumor (scale 0-3) and the presence or absence of lymph node metastases (scale 1-5) was evaluated for CT, MR, PET/CT and a combination of MR and PET to ensure that the MR-PET fusion does not cause a loss of diagnostic capability. PET was used to identify distant metastases. The PET dataset for simulated MR/PET was based on a segmentation of the CT data into 4 classes according to the approach of the Dixon MR-sequence for MR-PET. Standard of reference was histopathology in 19 cases. In one case no histopathological confirmation of a primary tumor could be achieved. RESULTS: Mean imaging time was 35:17 min (range: 31:08-42:42 min) for the protocol including sequences for local staging and attenuation correction and 44:17 min (range: 35:44-54:58) for the extended protocol. Although not statistically significant a combination of MR and PET performed better in the delineation of the primary tumor (mean 2.20) compared to CT (mean 1.40), MR (1.95) and PET/CT (2.15) especially in patients with dental implants. PET/CT and combining MR and PET performed slightly better than CT and MR for the assessment of lymph node metastases. Two patients with distant metastases were only identified by PET. CONCLUSION: We established a potential MR-protocol to be used for HNSCC patients in a recently introduced MR-PET scanner. The proposed protocol can be performed in an acceptable time frame and did not lead to a loss of diagnostic capability compared to PET/CT. PMID- 22078794 TI - The relationship between positive development and psychopathology during the transition to adulthood: a person-centred approach. AB - The transition to adulthood is characterised by potential for both positive development and problem outcomes such as psychopathology, yet little is known about relationships between the two. Given the diversity of pathways observed during this transition period, there is likely to be significant heterogeneity in young people's experiences of these outcomes. Drawing on data from 1158 19-20 year olds in the Australian Temperament Project and using latent profile analysis, we identified six subgroups. For most, higher positive development was associated with lower psychopathology and vice versa. One group (33.6%) was high across all positive development measures and low on psychopathology, and another (47.7%) average in both areas. The remaining four groups were low on positive development but differentiated by average psychopathology (4.7%), high internalising (5.5%), and moderate (7.2%) and severe (1.3%) externalising problems. Tailored intervention strategies that address both the promotion of competence and prevention of problem outcomes are needed. PMID- 22078795 TI - Preeclampsia activates 15-lipoxygenase and its metabolite 15 hydroxyeicosatetraenoic acid enhances constriction in umbilical arteries. AB - OBJECTIVE: To compare the differential expression of 15-lipoxygenase (15-LO) isoenzymes, 15-LO-1 and 15-LO-2 in preeclampsia (PE), and normal pregnancy and its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) on the vasoconstriction of human umbilical artery (HUA) rings. STUDY DESIGN: We performed western blotting and isometric tension studies and t-test analysis on data from 6 women with normal pregnancy and 8 women with PE. RESULTS: Expressions of 15-LO-1 and 15 LO-2 in placentas and HUA rings in PE increased more than that in normal groups (P<0.01). 15-HETE increased HUA rings tension in a dose-dependence manner, which were significantly greater in PE than in normal pregnant controls (P<0.01). However, the constriction of HUA rings was completely eliminated by 2 aminoethoxydiphenyl borate (2-APB) in both normal pregnancy and PE (P<0.01) and attenuated partly by nifedipine in dose-dependence in normal pregnancy (10( 8)mol/L P>0.05; 10(-7), 10(-6)mol/L P<0.05) and in PE (P<0.01). CONCLUSION: PE upregulates 15-LO pathway via 15-HETE, which increased intercellular calcium level to cause constriction of HUA rings. PMID- 22078796 TI - Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study. AB - Diffusion tensor imaging (DTI) detects white matter damage in neuro-psychiatric disorders, but data on reliability of DTI measures across more than two scanners are still missing. In this study we assessed multicenter reproducibility of DTI acquisitions based on a physical phantom as well as brain scans across 16 scanners. In addition, we performed DTI scans in a group of 26 patients with clinically probable Alzheimer's disease (AD) and 12 healthy elderly controls at one single center. We determined the variability of fractional anisotropy (FA) measures using manually placed regions of interest as well as automated tract based spatial statistics and deformation based analysis. The coefficient of variation (CV) of FA was 6.9% for the physical phantom data. The mean CV across the multicenter brain scans was 14% for tract based statistics, and 29% for deformation based analysis. The degree of variation was higher in less organized fiber tracts. Our findings suggest that a clinical and physical phantom study involving more than two scanners is indispensable to detect potential sources of bias and to reliably estimate effect size in multicenter diagnostic trials using DTI. PMID- 22078797 TI - Transmembrane mutations in Toll-like receptor 9 bypass the requirement for ectodomain proteolysis and induce fatal inflammation. AB - Recognition of nucleic acids as a signature of infection by Toll-like receptors (TLRs) 7 and 9 exposes the host to potential self-recognition and autoimmunity. It has been proposed that intracellular compartmentalization is largely responsible for reliable self versus nonself discrimination by these receptors. We have previously shown that TLR9 and TLR7 require processing prior to activation, which may further reinforce receptor compartmentalization and tolerance to self, yet this possibility remains untested. Here we report that residues within the TLR9 transmembrane (TM) region conferred the requirement for ectodomain proteolysis. TLR9 TM mutants responded to extracellular DNA, and mice expressing such receptors died from systemic inflammation and anemia. This inflammatory disease did not require lymphocytes and appeared to require recognition of self-DNA by dendritic cells. To our knowledge, these results provide the first demonstration that TLR-intrinsic mutations can lead to a break in tolerance. PMID- 22078798 TI - Flt3 signaling-dependent dendritic cells protect against atherosclerosis. AB - Early events in atherosclerosis occur in the aortic intima and involve monocytes that become macrophages. We looked for these cells in the steady state adult mouse aorta, and surprisingly, we found a dominance of dendritic cells (DCs) in the intima. In contrast to aortic adventitial macrophages, CD11c(+)MHC II(hi) DCs were poorly phagocytic but were immune stimulatory. DCs were of two types primarily: classical Flt3-Flt3L signaling-dependent, CD103(+)CD11b(-) DCs and macrophage-colony stimulating factor (M-CSF)-dependent, CD14(+)CD11b(+)DC-SIGN(+) monocyte-derived DCs. Both types expanded during atherosclerosis. By crossing Flt3(-/-) to Ldlr(-/-) atherosclerosis-prone mice, we developed a selective and marked deficiency of classical CD103(+) aortic DCs, and they were associated with exacerbated atherosclerosis without alterations in blood lipids. Concomitantly, the Flt3(-/-)Ldlr(-/-) mice had fewer Foxp3(+) Treg cells and increased inflammatory cytokine mRNAs in the aorta. Therefore, functional DCs are dominant in normal aortic intima and, in contrast to macrophages, CD103(+) classical DCs are associated with atherosclerosis protection. PMID- 22078799 TI - Receptor-like tyrosine phosphatases CD45 and CD148 have distinct functions in chemoattractant-mediated neutrophil migration and response to S. aureus. AB - Neutrophils, critical innate immune effectors, use bacterial-derived chemoattractant-induced G protein-coupled receptor (GPCR) signaling for their pursuit of bacteria. Tyrosine phosphorylation pathways and receptor-like tyrosine phosphatases (RPTPs) are rarely considered in chemoattractant-mediated GPCR signaling. Here, we report that two RPTPs, CD45 and CD148, previously shown to share redundant roles in positively regulating Src family kinases (SFKs) in immunoreceptor signaling pathways in B cells and macrophages, are critical in the neutrophil response to S. aureus infection and, surprisingly, in chemoattractant mediated chemotaxis. Remarkably, deficiency in either of these RPTPs influenced neutrophil GPCR responses in unique ways. Our results reveal that CD45 positively while CD148 positively and negatively regulate GPCR function and proximal signals including Ca(2+), phosphatidylinositol 3'OH kinase (PI3K), and phospho extracellular regulated kinase (pERK) activity. Moreover, our results suggest that CD45 and CD148 preferentially target different SFK members (Hck and Fgr versus Lyn, respectively) to positively and negatively regulate GPCR pathways. PMID- 22078801 TI - [Respiratory tract infections and travels]. PMID- 22078800 TI - A comparison of daily and occasional smokers' implicit affective responses to smoking cues. AB - Previous research has not compared implicit affective responses to smoking related stimuli in occasional (i.e., those who smoke less than one cigarette per day) and daily smokers (i.e., those who smoke at least once per day). In addition to assessing their motivations for smoking, implicit affective responses were measured using the Affect Misattribution Procedure (AMP) in occasional (n=19) and daily smokers (n=34) to smoking-related and neutral cues. Half of the cues depicted a human interacting with an object (i.e., active), whereas the remaining cues depicted objects alone (i.e., inactive). Results indicated that for the active cues, daily smokers responded more positively to smoking-related than to neutral cues, whereas occasional smokers showed no difference in their implicit responses. In addition to smoking frequency, relative differences in implicit responses to active cues were related to cognitive enhancement motivation. For inactive cues, implicit responses were related to cognitive enhancement as well as reinforcement. Because daily smokers have more positive implicit responses to active smoking-related cues than occasional smokers, these cues may play an important role in maintaining smoking behavior in daily smokers. PMID- 22078802 TI - [Dermatologic manifestations of the antiphospholipid syndrome]. AB - A wide variety of dermatologic manifestations has been described in the antiphospholipid syndrome (APS). The most frequent skin lesion is livedo reticularis, present not only on the limbs but also on the trunk, with a fine irregular pattern. It belongs to the arterial subset of APS. Circumscribed ulcerations, resembling livedoid vasculitis, may be the first manifestation of APS. Ulcerations may also occur as a late complication of recurrent venous thrombosis. Extensive skin necrosis is a classic manifestation of catastrophic APS. Pseudo-vasculitis lesions are misdiagnosed if a skin biopsy is not performed, especially in the context of systemic lupus erythematosus. In systemic lupus erythematosus, primary anetoderma is always associated with antiphospholipid antibodies. PMID- 22078803 TI - The use of Suprathel((r)) in deep dermal burns: first results of a prospective study. AB - INTRODUCTION: While autologous skin grafting has been the standard for coverage of full-thickness areas, several options for deep-partial-thickness defects exist. With regard to economising donor sites, we compared a copolymer based on DL-lactid acid (Suprathel((r))) as temporary wound dressing with autologous skin, and analysed time to healing and scar quality in matched areas of deep-partial thickness burn. METHODS: We recruited 18 patients with a median age of 45 years (range: 25-83 years), for this prospective, non-blinded controlled non inferiority study, suffering from deep-partial-thickness burns from November 2009 to July 2010. After early tangential excision, matched deep-partial-thickness areas were covered with 1:1.5 meshed autologous skin grafts and the copolymer for direct intra-individual comparison. Scars were evaluated by means of the Vancouver Scar Scale (VSS), the Patient and Observer Scar Assessment Scale (POSAS) and suction cutometry (MPA 580, Courage and Khazaka Electronic GmbH, Cologne, Germany) on days 30 and 90, postoperatively. RESULTS: Fifteen days after surgery, complete wound closure was present in 44.4% (8/18) of all areas covered with copolymer and 88.9% (16/18) in the split-thickness skin graft (STSG) area (p=0.008). Evaluation of the total VSS, POSAS and cutometry satisfied the criterion of non-inferiority for Suprathel((r)) on day 30. Ninety days after surgery, only the Observer Scar Scale showed that Suprathel is non-inferior to STSG, albeit the mean total VSS and Patient Scar Scale were better in Suprathel((r)) areas. CONCLUSION: Suprathel((r)) represents a solid, reliable epidermal skin substitute with longer healing times in comparison to skin grafts but comparable results concerning early scar formation. Suprathel((r)) can serve as a tool in treatment portfolio for adult patients suffering from deep dermal burns. Especially in patients with extensive burns, Suprathel((r)) can be used to cover the deep dermal burn wounds to save STSGs and its donor sites for the coverage of full-thickness burned areas. PMID- 22078804 TI - A systematic review of the evidence for telemedicine in burn care: with a UK perspective. AB - A comprehensive systematic review of telemedicine in burn care was carried out. Studies published between 1993 and 2010 were included. The main outcome measures were the level of evidence, technical feasibility, clinical feasibility, clinical management and cost effectiveness. The search strategy yielded 24 studies, none of which were randomised. There were only five studies with a control group, and in three of these the patients act as their own controls. Four studies performed quantitative cost analysis, and five more provide qualitative cost analysis. All studies demonstrate technical and clinical feasibility. If the significant potentials of telemedicine to assist in the acute triage, management guidance and outpatient care are to be realised, then research needs to be undertaken to provide evidence for such investment. PMID- 22078805 TI - Predictors of health-care needs in discharged burn patients. AB - Patients' health-care needs are an important issue, but have not been studied in the burn field. The aims of this study were to explore discharged burn patients' health-care needs and related factors. This cross-sectional study used convenience sampling and four questionnaires, including basic information, Mental Status Inventory, Burn Patients' Social Support and Burn Patients' Healthcare Needs for data collection. There were 93 adults, injured on average 45% of total body surface area, who completed the study. Results indicated that the level of psychosocial care needs were higher than physiological needs. The level of physiological care needs changed over time, but psychosocial needs did not change. Self-reported psychosocial needs and physiological care needs correlated with each other. The multiple regressions showed that the most important predictors of overall health-care needs were numbers of visible scarred areas, time since discharge and previous psychiatric history. The findings revealed the burn patients provided clinically useful information and supported further evaluation in the area of care needs for burn patients. PMID- 22078806 TI - Molecular characterization and antiviral activity test of common drugs against echovirus 18 isolated in Korea. AB - Genetic diversity and antiviral activity for five common antiviral drugs of echovirus (ECV) 5 isolated in Korea have been described. The present study extended these tests to a Korean ECV 18 isolate. An outbreak of aseptic meningitis caused by the ECV 18 isolate was reported in Korea in 2005, marking the first time this virus had been identified in the country since enterovirus surveillance began in 1993. Using a sample isolated from stool specimen of a 5 year-old male patient with aseptic meningitis, the complete genome sequence was obtained and was compared it with the Metcalf prototype strain. Unlike the ECV5 isolate, the 3' untranslated region had the highest identity value (94.2%) at the nucleotide level, while, at the amino acid level, the P2 region displayed the highest identity value (96.9%). These two strains shared all cleavage sites, with the exception of the 2B/2C site, which was RQ/NN in the Metcalf strain but RQ/NS in the Korean ECV 18 isolate. In Vero cells infected with the Korean ECV 18 isolate, no cytotoxicity was observed in the presence of azidothymidine, acyclovir, amantadine, lamivudine, or ribavirin, when the drugs were administered at a CC50 value >100 MUg/mL. Of the five drugs, only amantadine (IC50: 4.97 +/- 0.77 MUg/mL, TI: 20.12) and ribavirin (IC50: 7.63 +/- 0.87 MUg/mL, TI: 13.11) had any antiviral activity against the Korean ECV 18 isolate in the five antiviral drugs. These antiviral activity effects were similar with results of the Korean ECV5 isolate. PMID- 22078807 TI - The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs. AB - Three-dimensional (3D) culture could partially simulate in vivo conditions. In this work, we developed a 3D collagen scaffold to investigate cellular properties of MCF-7 cells. The porous scaffolds not only induced the diversification of cell morphologies but also extended cell proliferation. The expression of pro angiogenic growth factors and the transcriptions of matrix metalloproteinases (MMPs) were significantly increased in cells cultured in 3D collagen scaffolds. In addition, 3D collagen scaffolds could generate a cell population with the properties of cancer stem cells (CSCs). The upregulation of EMT markers and the downregulation of the epithelial cell marker were observed in cells cultured in collagen scaffolds. The expression of stem cell markers, including OCT4A and SOX2, and breast cancer stem cell signatures, including SOX4, JAG1 and CD49F, was significantly unregulated in 3D collagen scaffolds. The proportion of cells with CSC-like CD44(+)/CD24(-/low) phenotype was notably increased. High-level expression of CSC-associated properties of MCF-7 cells cultured in 3D was further confirmed by high tumorigenicity in vivo. Moreover, xenografts with 3D cells formed larger tumors. The properties of MCF-7 cells in 3D may have partially simulated their in vivo behaviors. Thus, 3D collagen scaffolds might provide a useful platform for anti-cancer therapeutics and CSC research. PMID- 22078808 TI - Control of cell attachment on pH-responsive chitosan surface by precise adjustment of medium pH. AB - The purpose of this study is to demonstrate pH-responsive chitosan is able to control cell behavior in response to small changes in environmental pH, which is at useful pH suitable for recovering cultured cells without additional enzymatic treatment and extensive washing steps. HeLa cells attached and spread well on chitosan at pH 6.99 and 7.20. When the pH was increased to 7.65, over 90% of cells would rapidly detached from chitosan surface within 1 h. Similarly, fibronectin adsorbed on chitosan at pH 7.20 also rapidly desorbed after increasing the medium pH. Most importantly and interestingly, medium pH adjustment could be facilitated by altering environment pCO(2). It was found over 80% of HeLa cells could be recovered from chitosan surface within 1 h and the viability of detached cells was more than 95% by transferring the culture plate from incubator to atmospheric condition. Additionally, chitosan substrate could effectively control attachment/detachment of various types of cells including cell lines HaCaT, H1299, NIH-3T3, and primary corneal fibroblasts, indicating the technology described here is easily reproducible and should be promising for controlling rapid fibronectin adsorption/desorption and cell attachment/detachment for tissue engineering applications. PMID- 22078809 TI - Recovery of cardiac function mediated by MSC and interleukin-10 plasmid functionalised scaffold. AB - Stem cell transplantation has been suggested as a treatment for myocardial infarction, but clinical studies have yet to demonstrate conclusive, positive effects. This may be related to poor survival of the transplanted stem cells due to the inflammatory response following myocardial infarction. To address this, a scaffold-based stem cell delivery system was functionalised with anti inflammatory plasmids (interleukin-10) to improve stem cell retention and recovery of cardiac function. Myocardial infarction was induced and these functionalised scaffolds were applied over the infarcted myocardium. Four weeks later, stem cell retention, cardiac function, remodelling and inflammation were quantified. Interleukin-10 gene transfer improved stem cell retention by more than five-fold and the hearts treated with scaffold, stem cells and interleukin 10 had significant functional recovery compared to the scaffold control (scaffold: -10 +/- 7%, scaffold, interleukin-10 and stem cells: +7 +/- 6%). This improved function was associated with increased infarcted wall thickness and increased ratios of collagen type III/type I, decreased cell death, and a change in macrophage markers from mainly cytotoxic in the scaffold group to mainly regulatory in scaffold, stem cells and interleukin-10 group. Thus, treatment of myocardial infarction with stem cells and interleukin-10 gene transfer significantly improved stem cell retention and ultimately improved overall cardiac function. PMID- 22078811 TI - The cytotoxicity of cadmium-based quantum dots. AB - Semiconductor Quantum dots (QDs) have raised great attention because of their superior optical properties and wide utilization in biological and biomedical studies. More recently, there have been intense concerns on cytotoxicity assessment of QDs. Most QDs are made of heavy metal ions (e.g., Cd(2+)), which may result in potential in vitro toxicity that hampers their practical applications. In this article, we aim to summarize recent progress on mechanistic studies of cytotoxicity of II-IV QDs. We have studied the cytotoxicity of a series of aqueous synthesized QDs (aqQDs), i.e. CdTe, CdTe/CdS core-shell structured and CdTe/CdS/ZnS core-shell-shell structured aqQDs. Our results suggested that released cadmium ions are responsible for the observed cytotoxicity of cadmium-based QDs. The fact that CdTe/CdS/ZnS core-shell-shell structured QDs are nearly nontoxic to cells further confirmed the role of released cadmium ions on cytotoxicity, and the effective protection of the ZnS shell. However, intracellular level of Cd(2+) ions cannot be the only reason since the comparison with CdCl(2)-treated cells suggests there are other factors contributed to the cytotoxicity of aqQDs. Our studies on genome-wide gene expression profiling and subcellular localization of aqQDs with synchrotron-based scanning transmission X-ray microscopy (STXM) further suggest that the cytotoxicity of CdTe QDs not only comes from the release of Cd(2+) ions but also intracellular distribution of QD nanoparticles in cells and the associated nanoscale effects. PMID- 22078810 TI - An activatable multimodal/multifunctional nanoprobe for direct imaging of intracellular drug delivery. AB - Multifunctional nanoparticles integrated with imaging modalities (such as magnetic resonance and optical) and therapeutic drugs are promising candidates for future cancer diagnostics and therapy. While targeted drug delivery and imaging of tumor cells have been the major focus in engineering nanoparticle probes, no extensive efforts have been made towards developing sensing probes that can confirm and monitor intracellular drug release events. Here, we present quantum dot (Qdot)-iron oxide (IO) based multimodal/multifunctional nanocomposite probe that is optically and magnetically imageable, targetable and capable of reporting on intracellular drug release events. Specifically, the probe consists of a superparamagnetic iron oxide nanoparticle core (IONP) decorated with satellite CdS:Mn/ZnS Qdots where the Qdots themselves are further functionalized with STAT3 inhibitor (an anti-cancer agent), vitamin folate (as targeting motif) and m-polyethylene glycol (mPEG, a hydrophilic dispersing agent). The Qdot luminescence is quenched in this nanocomposite probe ("OFF" state) due to combined electron/energy transfer mediated quenching processes involving IONP, folate and STAT3 agents. Upon intracellular uptake, the probe is exposed to the cytosolic glutathione (GSH) containing environment resulting in restoration of the Qdot luminescence ("ON" state), which reports on uptake and drug release. Probe functionality was validated using fluorescence and MR measurements as well as in vitro studies using cancer cells that overexpress folate receptors. PMID- 22078812 TI - Cisplatin@US-tube carbon nanocapsules for enhanced chemotherapeutic delivery. AB - The use of chemotherapeutic drugs in cancer therapy is often limited by problems with administration such as insolubility, inefficient biodistribution, lack of selectivity, and inability of the drug to cross cellular barriers. To overcome these limitations, various types of drug delivery systems have been explored, and recently, carbon nanotube (CNT) materials have also garnered attention in the area of drug delivery. In this study, we describe the preparation, characterization, and in vitro testing of a new ultra-short single-walled carbon nanotube (US-tube)-based drug delivery system for the treatment of cancer. In particular, the encapsulation of cisplatin (CDDP), a widely-used anticancer drug, within US-tubes has been achieved, and the resulting CDDP@US-tube material characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and inductively-coupled optical emission spectrometry (ICP-OES). Dialysis studies performed in phosphate-buffered saline (PBS) at 37 degrees C have demonstrated that CDDP release from CDDP@US-tubes can be controlled (retarded) by wrapping the CDDP@US-tubes with Pluronic-F108 surfactant. Finally, the anticancer activity of pluronic-wrapped CDDP@US-tubes has been evaluated against two different breast cancer cell lines, MCF-7 and MDA-MB-231, and found to exhibit enhanced cytotoxicity over free CDDP after 24 h. These studies have laid the foundation for developing US-tube-based delivery of chemotherapeutics, with drug release mainly limited to within cancer cells only. PMID- 22078814 TI - Magnetic resonance imaging versus endoscopic ultrasonography for the detection of pancreatic tumours in multiple endocrine neoplasia type 1. AB - OBJECTIVE: In multiple endocrine neoplasia type 1, the main risk factor for metastases is pancreatic tumour size. We and others recommend limiting surgery to non-functioning pancreatic tumors >=20 mm or growing, based on their size measured with endoscopic ultrasonography. Because endoscopic ultrasonography is invasive, we compared endoscopic ultrasonography (EUS) to non-invasive magnetic resonance imaging (MRI) for the detection of pancreatic tumours >=10 mm in multiple endocrine neoplasia type 1 patients. METHODS: A prospective study was performed in nine participating centres; 90 patients with multiple endocrine neoplasia type 1 underwent EUS and MRI with gadolinium infusion. Gastroenterologists and radiologists were blinded to the results, magnetic resonance images were reviewed centrally. RESULTS: EUS detected 86 tumours >=10 mm, and 48 (53.3%) patients had at least one tumour >=10 mm. MRI detected 67 tumours >=10 mm, and 46 (51.1%) patients had at least one tumour >=10 mm. EUS and MRI agreement was moderate for detection of tumours >=10 mm (Kappa coefficient=0.49), and for selection of patients with tumours >=10 mm (Kappa coefficient=0.55). EUS and MRI missed 11/24 and 4/24 lesions >=20 mm, respectively. EUS failed to identify 9/57 (15.7%) patients with pancreatic tumours >=10 mm, and MRI failed to identify 11/57 (19.3%) patients with pancreatic tumours >=10 mm. CONCLUSIONS: EUS and MRI are complementary and should be performed at initial evaluation in multiple endocrine neoplasia type 1 patients. Whether follow-up should be based on either technique or both, requires further evaluation. PMID- 22078813 TI - The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells. AB - Corneal stroma is an avascular connective tissue characterized by layers of highly organized parallel collagen fibrils, mono-disperse in diameter with uniform local interfibrillar spacing. Reproducing this level of structure on a nano- and micro-scale may be essential to engineer corneal tissue with strength and transparency similar to that of native cornea. A substrate of aligned poly(ester urethane) urea (PEUU) fibers, 165 +/- 55 nm in diameter, induced alignment of cultured human corneal stromal stem cells (hCSSCs) which elaborated a dense collagenous matrix, 8-10 MUm in thickness, deposited on the PEUU substratum. This matrix contained collagen fibrils with uniform diameter and regular interfibrillar spacing, exhibiting global parallel alignment similar to that of native stroma. The cells expressed high levels of gene products unique to keratocytes. hCSSCs cultured on PEUU fibers of random orientation or on a cast film of PEUU also differentiated to keratocytes and produced abundant matrix, but lacked matrix organization. These results demonstrate the importance of topographic cues in instructing organization of the transparent connective tissue of the corneal stroma by differentiated keratocytes. This important information will help with design of biomaterials for a bottom-up strategy to bioengineer spatially complex, collagen-based nano-structured constructs for corneal repair and regeneration. PMID- 22078815 TI - Jejunal pseudomelanosis. PMID- 22078818 TI - Persistence and metallic composition of paint particles in sediments from a tidal inlet. AB - Concentrations of Cu, Pb, Sn and Zn have been determined in sediment (<500 MUm) and macroscopic paint particles (>500 MUm) retrieved from sections of two cores collected from a tidal inlet of the Plym estuary, southwest England. Paint particles contributed up to about 0.2% of the total mass retrieved from each section and were most abundant towards the base of the cores where, according to (210)Pb dating, deposition took place about a decade prior to sampling. Metal concentrations in the paint particles pooled from the sections were highly variable, typically spanning two orders of magnitude in each core, and were greatest for Cu and Zn (up to 460,000 and 170,000 MUg g(-1), respectively) due to their use in contemporary antifouling formulations applied to boat hulls. Concentrations of metals in the sediment were, however, relatively invariant, an effect attributed to the abundance and dispersion of microscopic paint particles throughout the cores. PMID- 22078820 TI - [The occupational radiation-induced cataract in five industrial radiographers]. AB - The industrial uses of ionizing radiation in Tunisia are expanding, especially in industry and most particularly in the nondestructive testing of welds. Thus workers operating in the non-destructive testing of welds may develop a radiation induced cataract varying in time to onset depending on the dose. OBJECTIVES: To describe the characteristics of the radiation-induced cataract in patients exposed to ionizing radiation, determine the risk factors of radiation-induced cataracts. METHODS: This was an anamnestic, clinical, and environmental study of five cases of radiation-induced cataract in workers employed in non-destructive testing of welds. RESULTS: This series of five cases had a mean age of 30.2 years and 5.53 years of work experience, ranging from 14 months to 15 years. All the patients were male and industrial radiographers specialized in nondestructive testing of welds. The average duration of exposure to ionizing radiation was 5.53 years. None of the patients had worn protective gear such as eye goggles. The ophthalmic check-up for the five special industrial radiographers showed punctuate opacities in three cases, punctiform opacities in one eye in one case, and phacosclerosis with bilateral lens multiple crystalline stromal opacities in a case of micro-lens opacities in both eyes with opalescence of both eyes in one case. These cataracts had been declared as occupational diseases. CONCLUSION: The value of a specialized ophthalmologic surveillance among these workers and the early diagnosis of lens opacities must be emphasized. PMID- 22078821 TI - Clinically irrelevant circulating human leukocyte antigen antibodies in the presence of ventricular assist devices. AB - INTRODUCTION: Identification of anti-human leukocyte antigen (HLA) antibodies by single-antigen beads (SAB) allows for prediction of donor-specific crossmatches (virtual crossmatches), thus facilitating the allocation of organs from deceased donors. However, the clinical relevance of HLA antibodies identified by SAB has been less than clear. This study demonstrates that sera from cardiac transplant candidates with a ventricular assist device (VAD) or infection may contain clinically irrelevant antibodies that bind to the beads but not to lymphocytes. METHODS: Investigated were 5 cardiac transplant candidates (3 with VAD, all with infections, and 1 retransplant) with positive HLA antibodies detected by SAB, but negative by cytotoxicity. To determine clinical relevance of the antibodies, flow cytometric crossmatches (FCXM) were performed. Untreated beads and elution buffer treated beads to dissociate the beta-2 microglobulin and the peptide from the heavy chain were used. RESULTS: The virtual crossmatch data were compared with data from actual FCXMs. Of 40 T-cell and B-cell FCXM, SAB-identified HLA antibodies were predictive for only 1 T-cell and 9 B-cell FCXM outcomes. Patients' sera contained a mixture of antibodies directed against cryptic epitopes on the heavy chain and exposed epitopes. The mean fluorescence intensity of antibodies varied from 1,040 to 11,000. CONCLUSIONS: Sera from cardiac transplant candidates with or without VAD may contain natural antibodies that do not bind to intact antigens on the cell surface. Therefore, great care must be exercised before denying a life-saving transplant to these patients simply on the basis of SAB results. PMID- 22078822 TI - There is no difference with regard to hard and/or soft tissue safety between oscillating-rotating powered brushes and manual toothbrushes. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Safety of oscillating-rotating powered brushes compared to manual toothbrushes: a systematic review. Van der Weijden FA, Campbell SL, Dorfer CE, Gonzalez-Cabezas C, Slot DE. J Periodontol 2011;82(1):5-24. REVIEWERS: Nada J. Farsi, BDS, MSc, Belinda Nicolau, DDS, PhD. PURPOSE/QUESTION: To compare the soft and/or hard tissue safety between manual and oscillating-rotating brushes through a systematic review of the pertinent literature. SOURCE OF FUNDING: Industry (Procter & Gamble). TYPE OF STUDY/DESIGN: Systematic review LEVEL OF EVIDENCE: Level 1: Good-quality, patient-oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Grade A: Consistent, good-quality patient-oriented evidence. PMID- 22078823 TI - Essential oil mouthwash (EOMW) may be equivalent to chlorhexidine (CHX) for long term control of gingival inflammation but CHX appears to perform better than EOMW in plaque control. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Essential oils compared to chlorhexidine with respect to plaque and parameters of gingival inflammation: a systematic review. Van Leeuwen MPC, Slot DE, Van der Weijden GA. J Periodontol 2011 Feb;82(2):174-94. Epub 2010 Nov 2. REVIEWER: Anthony L. Neely, DDS, MDentSc, PhD. PURPOSE/QUESTION: To determine whether essential oil mouthwash is comparable to chlorhexidine gluconate with respect to reducing plaque and gingival inflammation and promoting calculus accumulation and extrinsic staining. SOURCE OF FUNDING: Some support came from the Academic Center for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam. TYPE OF STUDY DESIGN: Systematic review with meta-analysis of data. LEVEL OF EVIDENCE: Level 1: Good quality, patient-oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Grade B: Inconsistent or limited-quality patient-oriented evidence. PMID- 22078824 TI - Stepwise excavation may enhance pulp preservation in permanent teeth affected by dental caries. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Ways of enhancing pulp preservation by stepwise excavation-a systematic review. Hayashi M, Fujitani M, Yamaki C, Momoi Y. J Dent 2011;39(2):95-107. Epub 2010 Dec 3. REVIEWER: Lars Bjorndal, DDS, PhD, Dr Odont PURPOSE/QUESTION: To determine the clinical effectiveness of stepwise excavation for pulp preservation SOURCE OF FUNDING: Japanese Society of Conservative Dentistry TYPE OF STUDY/DESIGN: Systematic review LEVEL OF EVIENCE: Level 2: Limited-quality patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Grade B: Limited-quality patient-oriented evidence. PMID- 22078825 TI - The effectiveness of lasers to reduce dentinal hypersensitivity remains unclear. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Effectiveness of laser in dentinal hypersensitivity treatment: a systematic review. Sgolastra F, Petrucci A, Gatto R, Monaco A. J Endod 2011;37(3):297-303. REVIEWER: Asbjorn Jokstad, DDS, PhD. PURPOSE/QUESTION: Do patients with dentinal hypersensitivity subjected to laser light application compared to placebo "light experience" reduced hypersensitivity or any adverse outcomes? SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Systematic review LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Grade B: Inconsistent or limited-quality patient-oriented evidence. PMID- 22078826 TI - Resin-modified glass-ionomer cement (RM-GIC) may provide greater caries preventive effect compared with composite resin, but high-quality studies are needed. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Caries-preventive effect of resin modified glass-ionomer cement (RM-GIC) versus composite resin: a quantitative systematic review. Yengopal V, Mickenautsch S. Eur Arch Paediatr Dent 2011;12(1):5-14. REVIEWER: David G. Pendrys, DDS, PhD. PURPOSE/QUESTION: Does light-cured resin-modified glass-ionomer cement provide a better caries preventive effect as compared with composite resin? SOURCE OF FUNDING: Information not available. TYPE OF STUDY/DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Grade B: Inconsistent, limited-quality patient-oriented evidence. PMID- 22078827 TI - Administration of articaine anesthesia may lead to superior profound pulpal anesthesia compared with lidocaine in adult patients. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The pulpal anesthetic efficacy of articaine versus lidocaine in dentistry: a meta-analysis. Brandt RG, Anderson PF, McDonald NJ, Sohn W, Peters MC. J Am Dent Assoc 2011;42(5):493-504. REVIEWER: Khaled Balto, BDS, DMSc PURPOSE/QUESTION: Does articaine anesthesia in the management of irreversible pulpitis result in superior pain control compared with the traditionally used lidocaine? SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Grade B: Inconsistent or limited-quality patient-oriented evidence. PMID- 22078828 TI - Blood loss following orthognathic surgery varies widely and sometimes transfusions are needed. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Blood loss in orthognathic surgery: a systematic review. Pineiro-Aguilar A, Somoza-Martin M, Gandara-Rey JM, Garcia Garcia A. J Oral Maxillofac Surg 2011;69(3):885-92. REVIEWER: Thomas B. Dodson, DMD, MPH PURPOSE/QUESTION: To determine the range of information available to help surgeons better prepare themselves, their patients, and the auxiliary support for orthognathic surgery and transfusion requirements SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Systematic review LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Grade C: Consensus, disease-oriented evidence, usual practice, expert opinion, or case series for studies of diagnosis, treatment, prevention, or screening. PMID- 22078829 TI - Glycemic control is not related to postextraction healing in patients with diabetes. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The relationship of glycemic control to the outcomes of dental extractions. Aronovich S, Skope L, Kelly J, Kyriakides T. J Oral Maxillofac Surg 2010;68:2955-61. REVIEWER: Kaumudi Joshipura, BDS, MS, ScD. PURPOSE/QUESTION: To determine whether glycemic control among patients with diabetes influences healing after tooth extraction. SOURCE OF FUNDING: Information not available. TYPE OF STUDY/DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Not applicable. PMID- 22078830 TI - Zinc-replacement therapy may not reduce oral pain in patients with zinc-deficient burning mouth syndrome (BMS). AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Zinc deficiency may be a cause of burning mouth syndrome as zinc replacement therapy has therapeutic effects. Cho GS, Han MW, Lee B, Roh J, Choi S, Cho K, et al. J Oral Pathol Med 2010;39(9):722 7. REVIEWERS: Vinodh Bhoopathi, BDS, MPH, DScD, Ana Karina Mascarenhas, BDS, MPH, DrPH PURPOSE/QUESTION: In patients with BMS and low serum zinc levels, does zinc replacement therapy reduce pain? Authors using an animal model also attempted to demonstrate a causal relationship between BMS and zinc deficiency SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Randomized controlled trial LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable. PMID- 22078831 TI - Orthognathic surgical treatment may produce improved temporomandibular functional status in adults with pretreatment dysfunction. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Factors of importance for the functional outcome in orthognathic surgery patients: a prospective study of 118 patients. Oland J, Jensen J, Melsen B. J Oral Maxillofac Surg 2010;68:2221-31. REVIEWER: Michael D. Martin, DMD, MSD, MPH, MA, PhD. PURPOSE/QUESTION: To examine the effect of orthognathic surgery on perceived and clinically assessed functional (TMJ-related) status in addition to patients' satisfaction with function after treatment. SOURCE OF FUNDING: Information not available. TYPE OF STUDY/DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 2: Limited-quality, patient oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Not applicable. PMID- 22078832 TI - Low-dose doxycycline plus additional therapies may lower systemic inflammation in postmenopausal women with periodontitis. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The effect of subantimicrobial-dose doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial. Payne JB, Golub LM, Stoner JA, Lee H-M, Reinhardt RA, Sorsa T, Slepian MJ. J Am Dent Assoc 2011;142;262-73. REVIEWER: Walter A. Bretz, DDS, PhD. PURPOSE/QUESTION: To determine whether long-term subantimicrobial-dose-doxycycline (SDD) periodontal therapy could reduce serum biomarkers of systemic inflammation and improve lipid profiles in postmenopausal women who have systemic osteopenia and chronic periodontitis. SOURCE OF FUNDING: NIH/NIDCR grant R01DE012872. TYPE OF STUDY/DESIGN: Randomized controlled trial. LEVEL OF EVIDENCE: Level 2: Limited quality, patient-oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Not applicable. PMID- 22078833 TI - Female and older adult patients (age >= 21 Years) had slower recovery after third molar surgery compared with males and younger adults in a US study. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Recovery after third-molar surgery: the effects of age and sex. Phillips C, Gelesko S, Proffit WR, White RP Jr. Am J Orthod Dentofacial Orthop 2010;138(6):700.e1-8 REVIEWERS: Poramate Pitak-Arnnop, DDS, PGDipClinSc (OMS), MSc, PhD, DSc Niels Christian Pausch, MD, DMD, PhD. PURPOSE/QUESTION: To assess the effects of age and gender on quality-of-life recovery after third-molar surgery in patients treated in either community practices or academic centers. SOURCE OF FUNDING: The Oral and Maxillofacial Surgery Foundation, the American Association of Oral and Maxillofacial Surgeons, and the Dental Foundation of North America. TYPE OF STUDY/DESIGN: Cohort study. LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence. STRENGTH OF RECOMMENDATION GRADE: Not applicable. PMID- 22078834 TI - Using toluidine blue as an adjunct to oral visual cancer screening among high risk individuals may lead to increased detection of oral submucous fibrosis. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: A community-based RCT for oral cancer screening with toluidine blue. Su WW, Yen AM, Chiu SY, Chen TH. J Dent Res 2010;89(9):933-7. REVIEWER: Mark D. Macek, DDS, DrPH PURPOSE/QUESTION: Does using toluidine blue as an adjunctive tool for oral visual cancer screening lead to higher detection rates of oral premalignant lesions among high-risk populations? SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Randomized controlled trial LEVEL OF EVIDENCE: Level 2: Limited-quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable. PMID- 22078835 TI - Computer-aided designed/computer-assisted manufactured (CAD/CAM) all-ceramic crowns appear to perform better than all-composite resin crowns following the first 3 years of placement. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Computer-aided designed/computer assisted manufactured composite resin versus ceramic single-tooth restorations: a 3-year clinical study. Vanoorbeek S, Vandamme K, Lijnen I, Naert I. Int J Prosthodont 2010;23(3):223-30. REVIEWER: J. Robert Kelly, DDS, MS, DMedSc PURPOSE/QUESTION: To ascertain the 3-year success and survival rates of all composite resin and all-ceramic single-tooth restorations manufactured with a CAD/CAM system SOURCE OF FUNDING: GC Corporation Europe and UNI-DENT University Hospitals Dental Laboratories, Leuven, Belgium, provided some support for this study TYPE OF STUDY/DESIGN: Cohort study LEVEL OF EVIDENCE: Level 2: Limited quality, patient-oriented evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable. PMID- 22078836 TI - Flapless dental implant surgery may improve hard and soft tissue outcomes. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: A 1-year prospective clinical study of soft tissue conditions and marginal bone changes around dental implants after flapless implant surgery. Jeong S-M, Choi B-H, Kim J, Xuan F, Lee D-H, Mo DY, et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111:41-6. REVIEWER: Richard Oliver, BDS, BSc, PhD, FDSRCPS, FDS(OS)RCPS PURPOSE/QUESTION: To evaluate the soft tissue and marginal bone levels after 1 year around dental implants placed using flapless surgery SOURCE OF FUNDING: Korea Science and Engineering Foundation (KOSEF) funded by the Korean Government TYPE OF STUDY/DESIGN: Case series LEVEL OF EVIDENCE: Level 3: Other evidence STRENGTH OF RECOMMENDATION GRADE: Grade C: Consensus, disease-oriented evidence, usual practice, expert opinion, or case series for studies of diagnosis, treatment, prevention, or screening. PMID- 22078837 TI - High PCR copy-counts of periodontal pathogens in saliva are associated with periodontal disease status. AB - ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Salivary infectious agents and periodontal disease status. Saygun I, Nizam SI, Keskiner N, Bal V, Kubar A, Acikel C, et al. J Periodont Res 2011:46:235-9. REVIEWER: Paul I. Eke, PhD, MPH, PhD. PURPOSE/QUESTION: To determine if salivary counts of 6 periodontal pathogens and Epstein-Barr virus could distinguish between persons with periodontal health, gingivitis, chronic periodontitis, and aggressive periodontitis. SOURCE OF FUNDING: Information not available. TYPE OF STUDY/DESIGN: Cross-sectional study LEVEL OF EVIDENCE: Level 3: Other evidence. STRENGTH OF RECOMMENDATION GRADE: Not applicable. PMID- 22078838 TI - Child abuse pediatrics: research, policy and practice. PMID- 22078839 TI - Promoting equity through primary care and health services research: honoring the legacy of Dr. Barbara Starfield. PMID- 22078840 TI - The only person in the room who looks like me. PMID- 22078841 TI - Augmented home exercise program for a 37-year-old female with a clinical presentation of femoroacetabular impingement. AB - Previous researchers have reported on the use of augmented home exercise programs with potential carry-over effects from manual therapy treatment. While there is no direct evidence to support augmented manual therapy, tangential evidence demonstrates that specific, supervised, and adherent exercises result in improved outcomes. The purpose of this case report is to describe an augmented home program simulating the manual techniques provided by the therapist. A 37-year-old female presented with symptoms and signs consistent with femoroacetabular impingement (FAI). Grade III lateral and inferior femoral glides decreased reported pain from 5/10 to 0/10. Given the immediate response to hip mobilizations, the patient was prescribed standing lateral glides and supine inferior glides of the hip with the use of a belt. During this time, the patient's Lower Extremity Functional Scale score improved from 74 to 78 and she reported increased ability to self-manage her symptoms. The immediate report of decreased pain helped determine the specific home program selected for this individual patient. This case highlights the importance of a specific augmented home exercise program unique to the individual patient resulting in self management of pain associated with FAI. PMID- 22078842 TI - Segmentation of 3D radio frequency echocardiography using a spatio-temporal predictor. AB - This paper presents an algorithm for segmenting left ventricular endocardial boundaries from RF ultrasound. Our method incorporates a computationally efficient linear predictor that exploits short-term spatio-temporal coherence in the RF data. Segmentation is achieved jointly using an independent identically distributed (i.i.d.) spatial model for RF intensity and a multiframe conditional model that relates neighboring frames in the image sequence. Segmentation using the RF data overcomes challenges due to image inhomogeneities often amplified in B-mode segmentation and provides geometric constraints for RF phase-based speckle tracking. The incorporation of multiple frames in the conditional model significantly increases the robustness and accuracy of the algorithm. Results are generated using between 2 and 5 frames of RF data for each segmentation and are validated by comparison with manual tracings and automated B-mode boundary detection using standard (Chan and Vese-based) level sets on echocardiographic images from 27 3D sequences acquired from six canine studies. PMID- 22078843 TI - Characterization of compounds and potential neuraminidase inhibitors from the n butanol extract of Compound Indigowoad Root Granule using ultrafiltration and liquid chromatography-tandem mass spectrometry. AB - The liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were used to identify the pharmacologically active n-butanol extract from Compound Indigowoad Root Granule. As a result, eighteen compounds belonging to various structural classes such as nucleosides, purines, flavonoids and amino acid were unambiguously identified. Then an in vitro neuraminidase (NA) inhibition assay was carried out to examine the inhibitory activity of the standard samples and extracts on NA. After which, ultrafiltration liquid chromatography with photodiode array detection coupled to electrospray ionization tandem mass spectrometry (ultrafiltration LC-MS/MS) was used to study NA inhibitory activity of standard flavones and n-butanol extract of Compound Indigowoad Root Granule. This method is highly selective and sensitive, and it could be used for characterization of bioactive compounds and botanical extracts. The result provides some enlightenment for the explanation of the antiviral activity of Compound Indigowoad Root Granule and some guidance for natural anti-influenza medicine development. PMID- 22078844 TI - Simultaneous detection of multiple mutations in epidermal growth factor receptor based on fluorescence quenching of quantum dots. AB - We have developed a simultaneous detection method for two common mutations in the epidermal growth factor receptor gene based on the fluorescence quenching phenomenon caused by aggregation of CdSe quantum dots. For detection of the in frame deletion in exon 19 and the L858R point mutation in exon 21, water-soluble CdSe quantum dots with two sizes were functionalized using four different types of probe oligonucleotides. Addition of target oligonucleotides with the deletion mutation in exon 19 into the suspensions caused crosslinking-induced aggregation of green-emitting quantum dots, followed by the fluorescence quenching while that with the L858R point mutation resulted in aggregation of yellow-emitting quantum dots. In addition, targets with both deletion and point mutations caused aggregation of both green- and yellow-emitting quantum dots. This method allows a simultaneous detection of mutations in exon 19 and 21 of EGFR gene in a single experiment. We found that minimum mutant concentration that could be detected by this method was as low as 2% for deletion mutation, and 5% for point mutation. PCR products of EGFR gene were also used to confirm that our method could be used to detect mutation in amplified DNA fragments. PMID- 22078845 TI - A novel combined thermometric and amperometric biosensor for lactose determination based on immobilised cellobiose dehydrogenase. AB - A novel method for lactose determination in milk is proposed. It is based on oxidation of lactose by cellobiose dehydrogenase (CDH) from the basidiomycete Phanerochaete chrysosporium, immobilised in an enzyme reactor. The reactor was prepared by cross-linking CDH onto aminopropyl-silanised controlled pore glass (CPG) beads using glutaraldehyde. The combined biosensor worked in flow injection analysis (FIA) mode and was developed for simultaneous monitoring of the thermometric signal associated with the enzymatic oxidation of lactose using p benzoquinone as electron acceptor and the electrochemically generated current associated with the oxidation of the hydroquinone formed. A highly reproducible linear response for lactose was obtained between 0.05 mM and 30 mM. For a set of more than 500 samples an R.S.D. of less than 10% was achieved. The assay time was ca. 2 min per sample. The sensor was applied for the determination of lactose in dairy milk samples (milk with a fat content of 1.5% or 3% and also "lactose free" milk). No sample preparation except dilution with buffer was needed. The proposed method is rapid, suitable for repeated use and allows the possibility to compare results from two different detection methods, thus providing a built-in quality assurance. Some differences in the response observed between the methods indicate that the dual approach can be useful in mechanistic studies of redox enzymes. In addition, a dual system opens up interesting possibilities for studies of enzyme properties and mechanisms. PMID- 22078846 TI - Treating anemia associated with chronic renal failure with erythropoiesis stimulators: recombinant human erythropoietin might be the best among the available choices. AB - Chronic renal failure (CRF) is a widespread medical problem commonly accompanied by a hypoproliferative anemia ("renal anemia") due to erythropoietin deficiency. Anemia greatly contributes to reduced quality of life (Hr-QoL) and high morbidity and mortality in CRF patients. Recombinant human erythropoietin (rHu-Epo) was introduced to medical practice some 20years ago. It enables correction of anemia (hemoglobin levels, Hb) with dramatic immediate (Hr-QoL improvement) and long term effects (reduced morbidity and mortality). Newer experimental data suggest that long-term benefits could be due not only to antianemic effect, but also to a direct organoprotective effect of (rHu)-Epo mediated through a receptor complex different from the "erythropoietic" erythropoietin receptor. During the last decade, two alternative treatments for renal anemia have been approved: darbepoetin and CERA. Both are direct agonists of the "erythropoietic" receptors and both were derived from rHu-Epo. Molecularly, they differ from rHu-Epo in that they are much larger molecules (darbepoetin is genetically modified rHu-Epo with a higher sugar content and CERA is pegylated rHu-Epo) with lower affinity for the erythropoietin receptor but with a longer circulating time. In terms of renal anemia correction, they are non-inferior to rHu-Epo and allow for less frequent dosing. They have never been compared to rHu-Epo regarding the long-term outcomes. It is hypothesized that regarding the long-term outcomes (morbidity, mortality), rHu-Epo might be superior to those larger molecules. The hypothesis is based on two types of observations. First, experimental data emphasize the role of small, erythropoietically less valuable rHu-Epo isoforms in its organoprotective effects. Second, clinical observations suggest that rHu-Epo enables for less variable Hb correction than the larger molecules, and pronounced within-subject Hb variability has been suggested as an independent predictor of poor long-term outcomes of renal anemia management. PMID- 22078847 TI - Lymphoepithelial carcinoma of the nasal cavity mimicking juvenile angiofibroma. AB - Juvenile angiofibroma, nasopharyngeal carcinoma (NPC) and lymphoepithelial carcinoma of the nasal cavity (LEC NC) all could be found as a hyper-vascular mass in the nasopharynx area. Performing biopsy for histopathologic confirmation is necessary in the case of NPC or LEC NC but could be fatal in the case of angiofibroma. In our case, a 21-year-old male who was suffering from unilateral nasal stuffiness and frequent epistaxis had a mass with an easily bleeding tendency in his right nasal cavity. Juvenile angiofibroma was suspected by clinical and radiologic examinations. We performed preoperative angiography and the feeding vessel from the right internal maxillary artery was obliterated with polyvinyl alcohol nanoparticle. The mass was completely removed endoscopically, and there was profound hemorrhage in spite of the preoperative embolization. The mass turned out to be LEC NC by postoperative histopathologic examination. To avoid this misdiagnosis, the authors suggest that we should perform biopsy under rigid endoscopy 24h after angiographic embolization. If the result of frozen biopsy is juvenile angiofibroma, we could perform surgery another 24h later. If the result is nasopharyngeal carcinoma or LEC NC, we could avoid unnecessary surgical removal and perform radiotherapy. In terms of treatment strategies, we suggest endoscopic removal of gross tumor and postoperative combination of chemoradiotherapy as the more curative regimen with less complications related with radiotherapy. PMID- 22078848 TI - A huge chondromyxoid fibroma of the nasal cavity in a newborn baby. AB - Chondromyxoid fibroma is a rare benign tumor that usually occurs in the long bones. A 2-month newborn presented with huge masses in the both nasal cavities, which turned out to be chondromyxoid fibroma. The masses originated from both inferior turbinates. Total turbinectomy on the left side and submucosal mass excision on the right side were performed. No recurrence or new lesion was observed during the 2 years of follow up. We report here on a rare case of nasal cavity chondromyxoid fibroma in a neonate and we review the relevant literature. PMID- 22078850 TI - Rotation vectors of slow and quick phase of caloric nystagmus. AB - OBJECTIVE: The purpose of this study was to elucidate the rotation axes of the slow and quick phase of the caloric nystagmus using the video-oculographic technique. METHODS: Subjects were placed in a supine position and cold-water stimulation was applied to the right ear canal. The eye movements were recorded in complete darkness by a high-speed infrared CCD camera. The sampling time of the camera was 132Hz with 640*480 effective pixels. RESULTS: The rotation vectors were calculated from the printed-out chart of the 3D analysis data of the caloric nystagmus. The directions of the rotation vector of the quick phase of the nystagmus were almost opposite to those of the slow phase. The average planer equations of the slow and quick phase of the nystagmus in all subjects were 0.399x+0.1477y-0.8656z=0 and -0.3970x-0.1940y+0.8559z=0, respectively. CONCLUSION: We demonstrated that the slow phase and quick phase of the vestibular nystagmus are along with the same axes in human subjects. PMID- 22078849 TI - Heme oxygenase-1 expression in chronic rhinosinusitis with eosinophilic infiltration. AB - OBJECTIVES: Chronic rhinosinusitis (CRS) with eosinophilic infiltration is a type of intractable rhinosinusitis often associated with asthma. The oxidants are well known to induce aggravate asthma. Heme oxygenase-1 (HO-1), a cytoprotective enzyme against oxidant, has been extensively studied in airway diseases. However, no study that observed HO-1 in both epithelial and subepithelial tissues of CRS has been reported. METHODS: Part of each specimen derived from the nasal polyps of CRS with and without eosinophilic infiltration was promptly fixed for hematoxylin-eosin staining and immunohistochemical analysis for HO-1 and macrophages. RESULTS: We found that the expression of HO-1 in the epithelial layers of CRS without eosinophilic infiltration was significantly enhanced as compared with that of CRS with eosinophilic infiltration. On the other hand, the number of macrophages with HO-1 positive reactions was significantly greater in CRS with eosinophilic infiltration compared with CRS without eosinophilic infiltration. CONCLUSIONS: Our study suggests that both a reduction of HO-1 expression in epithelial cells and an increase of infiltration of macrophages positive for HO-1 are related to the epithelial damage of CRS with eosinophilic infiltration. PMID- 22078851 TI - Efficacy and safety of garenoxacin in the treatment of upper respiratory tract infections. AB - OBJECTIVE: To determine the efficacy and safety of garenoxacin, a new generation of quinolone antimicrobial agent, in the treatment of adult upper respiratory tract infections. METHODS: A total of 113 subjects were enrolled in this study. Garenoxacin (400mg/day) was administered to patients with pharyngolaryngitis, tonsillitis, and otitis media for 5-7 days and to those with sinusitis for 7-10 days. Clinical symptoms and findings were examined and quantitatively evaluated using a scoring system. RESULTS: We found 80 to 100% improvement rate in symptoms and findings for each infection. In addition, we found significant improvement in subjective evaluations from patient questionnaires even in the early stage of the treatment. X-ray examination for acute sinusitis demonstrated that the clinical efficacy was 84% (27/32) and 76% (19/25) patients were already improved within seven days. Among the detected 84 bacteria, 75 (89%) were identified as the major pathogenic bacteria of respiratory tract infections such as Streptococcus pneumoniae (27 strains) and Haemophillus influenzae (14 strains). Garenoxacin administration completely eradicated bacteria in 53 out of 54 cases (98%). There were 8 adverse events (8.3%) including 3 diarrhea cases (3.1%). CONCLUSION: These results suggest that garenoxacin is a highly effective and safe antimicrobial agent in the treatment of community-acquired upper respiratory infections. Additionally, garenoxacin did not induce the growth of resistant bacteria because of its strong antimicrobial activity. PMID- 22078853 TI - Reply to "A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned". PMID- 22078854 TI - Comparison of stent free cell area and cerebral lesions after unprotected carotid artery stent placement. AB - OBJECTIVE: This study evaluates the correlation between closed, semi-closed and open-cell stent design and the association between stent type and clinical outcome as well as magnetic resonance imaging (MRI) findings. DESIGN: A total of 194 patients who underwent unprotected carotid artery stenting (CAS) as well as diffusion-weighted magnetic resonance imaging (DW-MRI) before and after intervention were retrospectively reviewed. MATERIALS AND METHODS: Three stent designs were studied: closed cell, semi-closed cell and open cell. Spearman's Rho test was performed between the stent free cell area and the number and area of ischaemic lesions found after intervention. Adverse events were evaluated. RESULTS: There was no significant difference in clinical outcome between the three stent groups (Zilver, Cook Europe, Denmark; Smart, Codman, MA; and Wallstent, Stryker, MN, USA). A significant correlation was found between the stent free cell area and the number and area of new ischaemic lesions on DW-MRI (P = 0.023). There were significantly fewer new lesions with an open-cell design (Zilver; 12.76 mm(2) free cell area) than with a closed-cell design (Wallstent; 1.08 mm(2) free cell area). CONCLUSIONS: Open-cell stent was related to a lower number and area of silent cerebral ischaemic lesions after unprotected CAS. However, clinical outcome, measured by incidence of adverse events and clinical neurologic assessment, was not significantly different between patients with different stent designs. PMID- 22078855 TI - Bedside detection of awareness in the vegetative state: a cohort study. AB - BACKGROUND: Patients diagnosed as vegetative have periods of wakefulness, but seem to be unaware of themselves or their environment. Although functional MRI (fMRI) studies have shown that some of these patients are consciously aware, issues of expense and accessibility preclude the use of fMRI assessment in most of these individuals. We aimed to assess bedside detection of awareness with an electroencephalography (EEG) technique in patients in the vegetative state. METHODS: This study was undertaken at two European centres. We recruited patients with traumatic brain injury and non-traumatic brain injury who met the Coma Recovery Scale-Revised definition of vegetative state. We developed a novel EEG task involving motor imagery to detect command-following--a universally accepted clinical indicator of awareness--in the absence of overt behaviour. Patients completed the task in which they were required to imagine movements of their right-hand and toes to command. We analysed the command-specific EEG responses of each patient for robust evidence of appropriate, consistent, and statistically reliable markers of motor imagery, similar to those noted in healthy, conscious controls. FINDINGS: We assessed 16 patients diagnosed in the vegetative state, and 12 healthy controls. Three (19%) of 16 patients could repeatedly and reliably generate appropriate EEG responses to two distinct commands, despite being behaviourally entirely unresponsive (classification accuracy 61-78%). We noted no significant relation between patients' clinical histories (age, time since injury, cause, and behavioural score) and their ability to follow commands. When separated according to cause, two (20%) of the five traumatic and one (9%) of the 11 non-traumatic patients were able to successfully complete this task. INTERPRETATION: Despite rigorous clinical assessment, many patients in the vegetative state are misdiagnosed. The EEG method that we developed is cheap, portable, widely available, and objective. It could allow the widespread use of this bedside technique for the rediagnosis of patients who behaviourally seem to be entirely vegetative, but who might have residual cognitive function and conscious awareness. FUNDING: Medical Research Council, James S McDonnell Foundation, Canada Excellence Research Chairs Program, European Commission, Fonds de la Recherche Scientifique, Mind Science Foundation, Belgian French-Speaking Community Concerted Research Action, University Hospital of Liege, University of Liege. PMID- 22078856 TI - Measurements of consciousness in the vegetative state. PMID- 22078857 TI - [Case 42. Multifocal facial and orbital lymphoma]. PMID- 22078858 TI - [Case 48. Mild encephalitis/encephalopathy with an isolated reversible lesion of the corpus callosum splenium]. PMID- 22078859 TI - [Case 50. Dysplasia epiphysealis hemimelica]. PMID- 22078860 TI - [Case 41]. PMID- 22078861 TI - NMR field-cycling at ultralow magnetic fields. AB - The paper describes some significant technical improvements of a home built NMR field cycling relaxometer [O. Lips, A. Privalov, S. Dvinskikh, F. Fujara, J. Magn. Reson. 149 (2001) 22-28] now allowing for fast switching of polarization fields (up to more than 1T) to evolution fields down to the sub-MUT range. The most important instrumental details such as the description of an involved 3 dimensional resistive coil setup are given. Fields below about 5 MUT can only be stabilized by incorporation of an active field drift and fluctuation compensation tool. In this way, the smallest 1H Larmor frequency obtained and measured so far has been 12 Hz. PMID- 22078862 TI - Medication errors during patient transitions into nursing homes: characteristics and association with patient harm. AB - BACKGROUND: Patients transitioning to a nursing home from their home or other facility are at high risk for medication errors. OBJECTIVE: Our aim was to describe characteristics of medication errors occurring during transitions to nursing homes, to compare characteristics of transition errors with errors not involving a transition, and to evaluate the impact of these errors on patient harm. METHODS: This was a cross-sectional analysis of individual medication error incidents reported by North Carolina nursing homes to the Medication Error Quality Initiative during fiscal years 2007 through 2009. Bivariate associations between errors in transition with patient factors, error-related factors, reported causes of errors, and impact on patients were tested using a chi(2) test. Multivariate logistic regression explored whether medication errors during transitions were more harmful than errors not occurring during transitions. Patient-related factors included in the model were age, sex, and cognitive ability. Error-related factors were primary type of error, process phase when error began, primary personnel involved, and an indicator for repeat error. RESULTS: A total of 27,759 individual medication error incidents were reported over a 3-year period in North Carolina nursing homes. Of these errors, 2919 incidents (11%) involved a patient transitioning to a nursing home. Errors involved in transitions were found to have higher odds of patient harm compared with errors not involved in transitions (odds ratio = 1.85; 95% CI, 1.30-2.63). Staff communication, order transcription, medication availability, pharmacy issues, and name confusion were particularly important contributors to medication errors during transitions (P < 0.05 for comparison with nontransition errors). CONCLUSIONS: Transitions across care settings introduce risk for patient harm, and medication errors are an important area for improvement during transitions. PMID- 22078863 TI - Potentially harmful drug-drug interactions in the elderly: a review. AB - BACKGROUND: Elderly patients are vulnerable to drug interactions because of age related physiologic changes, an increased risk for disease associated with aging, and the consequent increase in medication use. OBJECTIVE: The purpose of this narrative review was to describe findings from rigorously designed observational cohort and case-control studies that have assessed specific drug interactions in elderly patients. METHODS: The PubMed and International Pharmaceutical Abstracts databases were searched for studies published in English over the past 10 years (December 2000-December 2010) using relevant Medical Subject Headings terms (aged; aged, 80 and over; and drug interactions) and search terms (drug interaction and elderly). Search strategies were saved and repeated through September 2011 to ensure that the most recent relevant published articles were identified. Additional articles were found using a search of review articles and reference lists of the identified studies. Studies were included if they were observational cohort or case-control studies that reported specific adverse drug interactions, included patients aged >=65 years, and evaluated clinically meaningful end points. Studies were excluded if they used less rigorous observational designs, assessed pharmacokinetic/pharmacodynamic properties, evaluated drug-nutrient or drug-disease interactions or interactions of drug combinations used for therapeutic benefit (eg, dual antiplatelet therapy), or had inconclusive evidence. RESULTS: Seventeen studies met the inclusion criteria. Sixteen studies reported an elevated risk for hospitalization in older adults associated with adverse drug interactions. The drug interactions included: angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics, ACE inhibitors or angiotensin receptor blockers and sulfamethoxazole/trimethoprim, benzodiazepines or zolpidem and interacting medications, calcium channel blockers and macrolide antibiotics, digoxin and macrolide antibiotics, lithium and loop diuretics or ACE inhibitors, phenytoin and sulfamethoxazole/trimethoprim, sulfonylureas and antimicrobial agents, theophylline and ciprofloxacin, and warfarin and antimicrobial agents or nonsteroidal anti-inflammatory drugs. One study reported the risk for breast cancer-related death as a function of paroxetine exposure among women treated with tamoxifen. CONCLUSIONS: Several population-based studies have reported significant harm associated drug interactions in elderly patients. Increased awareness and interventions aimed at reducing exposure and minimizing the risks associated with potentially harmful drug combinations are needed. PMID- 22078864 TI - [Therapeutic hypothermia after pediatric cardiac arrest]. AB - INTRODUCTION: Therapeutic hypothermia (TH) improves neurological outcome in adults after ventricular fibrillation cardiac arrest and in neonates with hypoxic ischemic encephalopathy. The effect of TH in children is under investigation. OBJECTIVES: To assess the feasibility, efficacy and safety of a pilot program of TH in pediatric cardiac arrest. MATERIAL AND METHODS: Prospective study in a pediatric intensive care unit. An external cooling method with a servo system was used on all patients according to an established protocol. Values expressed as median (IQ range). RESULTS: Six patients were included, of whom 5 had an out of hospital cardiac arrest. The mean age was 33 months (16-120) and Glasgow coma scale 6 (4-7). The T degrees prior to the induction of TH was 39.2 degrees C (39.1-39.4). The median T degrees used was 34.0 degrees C (33.5-34.8 degrees C), which was reached in 4h. (3-7) after the start and maintained for 48h. (45 54). The rewarming was carried out over a period of 14h. (12-16). Hypokalemia was the most common adverse event found. Five patients survived to hospital discharge with a Glasgow Coma Scale of 13 (11-14). At 6 months follow up the Pediatric Cerebral Performance Category score was <= 2 in three patients. CONCLUSION: In this pilot study, the use of mild therapeutic hypothermia with a protocol that included rapid sequence induction with an external surface cooling technique was feasible, effective and safe in children with cardiac arrest. PMID- 22078865 TI - Dissecting the journey: nursing student experiences with collaboration during the group work process. AB - Since the outset of nursing care, group work processes have evolved into essential components of a nurse's role and responsibilities within the health care system. To reflect this trend, group work is often utilized as a medium to promote professional socialization in undergraduate nursing curricula. The purpose of this qualitative study was to explore the ways undergraduate nursing students experience collaboration during group work activities. Braun and Clarke's (2006) theoretical thematic analysis combined with Pollio et al.'s (2006) interpretive framework was utilized to capture the students' lived experiences regarding group work. The participants of this study consisted of 96 undergraduate students enrolled in a nursing program in Canada. Written descriptions of their perceptions of their group work practices were analyzed to determine the extent to which these adhere to the collaborative practice essential elements (Jones and Way, 2006). Analysis of the results revealed an unexpected element of collaboration that of the psychosocial element in group work. The results from this study expose advantages and disadvantages of group work processes during group work in nursing education. This type of insight is valuable for educators to prepare nursing students for the complex demands of working with interdisciplinary teams. PMID- 22078866 TI - Student nurses' perceptions of how they learn drug calculation skills. AB - AIMS AND OUTCOMES: This study explored the area of learning styles in relation to drug calculations. Student nurses' perceptions of how they learn drug calculation skills were investigated in order to inform future teaching and learning strategies. METHODOLOGY: A semi-structured questionnaire was given to 67 student nurses to explore their perceptions of teaching and learning strategies implemented during a 2nd year nursing module. The results were analysed using descriptive statistics and grounded theory. RESULTS: From this analysis three main themes emerged; students being able to measure their skills and gain feedback about their progress; being able to learn in their 'own way' and being given opportunities for this to happen; and being focussed on the goal of being able to calculate drugs in the 'real world'. The implications of these findings are explored in relation to nurse education. PMID- 22078867 TI - Staff and students' perceptions and experiences of teaching and assessment in Clinical Skills Laboratories: interview findings from a multiple case study. AB - BACKGROUND: The Clinical Skills Laboratory has become an essential structure in nurse education and several benefits of its use have been identified. However, the literature identifies the need to examine the transferability of skills learned there into the reality of practice. OBJECTIVE: This research explored the role of the Clinical Skills Laboratory in preparing nursing students for the real world of practice. This paper focuses specifically on the perceptions of the teaching and assessment strategies employed there. DESIGN: Qualitative multiple case study design. SETTING: Five case study sites. PARTICIPANTS: Interviewees (n=58) included academic staff, clinical staff and nursing students. METHODS: Semi-structured interviews. RESULTS: The Clinical Skills Laboratory can provide a pathway to practice and its authenticity is significant. Teaching strategies need to incorporate communication as well as psychomotor skills. Including audio visual recording into assessment strategies is beneficial. Effective relationships between education institutions and clinical settings are needed to enhance the transferability of the skills learned. CONCLUSIONS: The Clinical Skills Laboratory should provide an authentic learning environment, with the appropriate use of teaching strategies. It is crucial that effective links between educators and clinical staff are established and maintained. PMID- 22078868 TI - Co-existence of multiple strains of porcine circovirus type 2 in the same pig from China. AB - Pigs are often co-infected by different viral strains from the same virus. Up to now, there are few reports about co-existence of different porcine circovirus type 2 (PCV2) strains in China. The aim of this study was to evaluate it in Chinese swine herds. 118 PCV2 positive DNAs isolated from diseased pigs identified by classic PCR were re-detected using a modified differential PCR assay. The results indicated that co-existence rates of PCV2 were 32.2% (38/118) in diseased pigs and 0% (0/41) in asymptomatic pigs. Four PCV2 complete genomes were cloned from two co-infected samples and their nucleotide (nt) identities were 95%-97.3%. The phylogenetic analysis showed that four PCV2 strains were divided into different genotypes, PCV2a, PCV2b, PCV2d and PCV2e, respectively. In addition, co-existence were not detected in 41 serum samples from healthy pigs but PCV2 single infection (31.7%, 13/41) existed. These data revealed that the co existence of different strains of PCV2 might contribute to the development of more severe clinical symptoms for pigs. This is the first report confirming the co-existence of different PCV2 strains in Chinese swine herds. Meanwhile, this study could help us to understand new infection and prevalence forms of PCV2 clinically. PMID- 22078869 TI - Options on fertility preservation in female cancer patients. AB - Infertility following treatment of cancer is a quality of survival's recognized issue and efforts should be made to help young cancer patients retaining their fertility potential. Options to preserve fertility in female patients include well established methods such as shielding to reduce radiation damage to reproductive organs, fertility-sparing surgery and emergency in vitro fertilization after controlled ovarian stimulation, aiming at freezing embryos. Transfer of frozen/thawed embryos today is a clinical routine in fertility clinics worldwide and it has been used for over 25 years. Mature oocytes after ovarian stimulation can also be frozen unfertilized, nevertheless overall pregnancy rates after fertilization of frozen-thawn oocytes are still relatively lower than those with embryo freezing. Remaining fertility preservation options are still in development and include the freezing of immature oocytes aiming at later in vitro maturing and fertilizing them and the cryopreservation of ovarian tissue for future retransplantation or for in vitro growth and maturation of follicles, both still experimental. PMID- 22078870 TI - Altered expression of neuropeptides in the primary somatosensory cortex of the Down syndrome model Ts65Dn. AB - Down syndrome is the most common genetic disorder associated with mental retardation. Subjects and mice models for Down syndrome (such as Ts65Dn) show defects in the formation of neuronal networks in both the hippocampus and the cerebral cortex. The principal neurons display alterations in the morphology, density and distribution of dendritic spines in the cortex as well as in the hippocampus. Several evidences point to the possibility that the atrophy observed in principal neurons could be mediated by changes in their inhibitory inputs and, in fact, an imbalance between excitation and inhibition has been observed in Ts65Dn mice in these regions, which are crucial for learning and information processing. These animals have an increased density of interneurons in the primary somatosensory cortex, especially of those expressing calretinin and calbindin D-28k. Here, we have analysed the expression and distribution of several neuropeptides in the primary somatosensory cortex of Ts65Dn mice in order to investigate whether these subpopulations of interneurons are affected. We have observed an increase in the total density of somatostatin expressing interneurons and of those expressing VIP in layer IV in Ts65Dn mice. The typology of the somatostatin and VIP interneurons was unaltered as attested by the pattern of co expression with other markers. Somatostatin immunoreactive neurons co-express mainly D-28k calbindin and VIP expressing interneurons maintain its pattern of co expression with calcium binding proteins. These alterations, in case they were also present in subjects with Down syndrome, could be related to their impairment in cognitive profile and could be involved in the neurological defects observed in this disorder. PMID- 22078871 TI - Derepressing nuclear receptors for metabolic adaptation. AB - NCoR is a corepressor of several transcription factors, including the PPAR family of nuclear receptors in fat and muscle. By specifically deleting NCoR in these tissues, Li et al. and Yamamoto et al. now uncover an important role for NCoR in regulating lipid homeostasis through the coordinated control of different nuclear receptors. PMID- 22078872 TI - New driver for lipid synthesis. AB - Cholesterol regulates activation of sterol regulatory element-binding protein (SREBP) through a classic feedback loop. Walker et al. (2011) extend the regulatory inputs governing SREBP activity to include an independent loop modulated by phosphatidylcholine (PC) and cellular methylation capacity. These findings suggest a link between lipid synthesis and cellular pathways involved in methylation. PMID- 22078873 TI - PINK1 and Parkin flag Miro to direct mitochondrial traffic. AB - The Parkinson's disease proteins PINK1 and Parkin are proposed guardians of mitochondrial fidelity, targeting damaged mitochondria for degradation by mitophagy. In this issue of Cell, Wang et al. (2011) now show that PINK1 and Parkin also regulate mitochondrial trafficking and quarantine damaged mitochondria by severing their connection to the microtubule network. PMID- 22078874 TI - Feedback on fat: p62-mTORC1-autophagy connections. AB - Metabolic homeostasis requires integration of multiple signals and cellular activities. Without this integration, conditions of obesity and diabetes often develop. Recent in vivo studies explore the molecular basis for metabolic homestasis, showing that p62 links autophagy and mTORC1 activation to regulate adipogenesis and energy control. PMID- 22078875 TI - Autophagy: renovation of cells and tissues. AB - Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation. We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease. PMID- 22078877 TI - The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. AB - Cancer stem cells (CSCs) are proposed to drive tumor initiation and progression. Yet, our understanding of the cellular and molecular mechanisms that underlie CSC properties is limited. Here we show that the activity of TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in breast CSCs. TAZ protein levels and activity are elevated in prospective CSCs and in poorly differentiated human tumors and have prognostic value. Gain of TAZ endows self-renewal capacity to non-CSCs. In epithelial cells, TAZ forms a complex with the cell-polarity determinant Scribble, and loss of Scribble--or induction of the epithelial-mesenchymal transition (EMT)--disrupts the inhibitory association of TAZ with the core Hippo kinases MST and LATS. This study links the CSC concept to the Hippo pathway in breast cancer and reveals a mechanistic basis of the control of Hippo kinases by cell polarity. PMID- 22078876 TI - Programmed cell death in animal development and disease. AB - Programmed cell death (PCD) plays a fundamental role in animal development and tissue homeostasis. Abnormal regulation of this process is associated with a wide variety of human diseases, including immunological and developmental disorders, neurodegeneration, and cancer. Here, we provide a brief historical overview of the field and reflect on the regulation, roles, and modes of PCD during animal development. We also discuss the function and regulation of apoptotic proteins, including caspases, the key executioners of apoptosis, and review the nonlethal functions of these proteins in diverse developmental processes, such as cell differentiation and tissue remodeling. Finally, we explore a growing body of work about the connections between apoptosis, stem cells, and cancer, focusing on how apoptotic cells release a variety of signals to communicate with their cellular environment, including factors that promote cell division, tissue regeneration, and wound healing. PMID- 22078879 TI - A quantitative model for ordered Cdk substrate dephosphorylation during mitotic exit. AB - After sister chromatid splitting at anaphase onset, exit from mitosis comprises an ordered series of events. Dephosphorylation of numerous mitotic substrates, which were phosphorylated by cyclin-dependent kinase (Cdk), is thought to bring about mitotic exit, but how temporal ordering of mitotic exit events is achieved is poorly understood. Here, we show, using budding yeast, that dephosphorylation of Cdk substrates involved in sequential mitotic exit events occurs with ordered timing. We test different models of how ordering might be achieved by modulating Cdk and Cdk-counteracting phosphatase Cdc14 activities in vivo, as well as by kinetic analysis of Cdk substrate phosphorylation and dephosphorylation in vitro. Our results suggest that the gradual change of the phosphatase to kinase ratio over the course of mitotic exit is read out by Cdk substrates that respond by dephosphorylation at distinct thresholds. This provides an example and a mechanistic explanation for a quantitative model of cell-cycle progression. PMID- 22078878 TI - ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. AB - Although eukaryotic nuclei contain distinct architectural structures associated with noncoding RNAs (ncRNAs), their potential relationship to regulated transcriptional programs remains poorly understood. Here, we report that methylation/demethylation of Polycomb 2 protein (Pc2) controls relocation of growth-control genes between Polycomb bodies (PcGs) and interchromatin granules (ICGs) in response to growth signals. This movement is the consequence of binding of methylated and unmethylated Pc2 to the ncRNAs TUG1 and MALAT1/NEAT2, located in PcGs and ICGs, respectively. These ncRNAs mediate assembly of multiple corepressors/coactivators and can serve to switch mark recognition by "readers" of the histone code. Additionally, binding of NEAT2 to unmethylated Pc2 promotes E2F1 SUMOylation, leading to activation of the growth-control gene program. These observations delineate a molecular pathway linking the actions of subnuclear structure-specific ncRNAs and nonhistone protein methylation to relocation of transcription units in the three-dimensional space of the nucleus, thus achieving coordinated gene expression programs. PMID- 22078880 TI - Adipocyte NCoR knockout decreases PPARgamma phosphorylation and enhances PPARgamma activity and insulin sensitivity. AB - Insulin resistance, tissue inflammation, and adipose tissue dysfunction are features of obesity and Type 2 diabetes. We generated adipocyte-specific Nuclear Receptor Corepressor (NCoR) knockout (AKO) mice to investigate the function of NCoR in adipocyte biology, glucose and insulin homeostasis. Despite increased obesity, glucose tolerance was improved in AKO mice, and clamp studies demonstrated enhanced insulin sensitivity in liver, muscle, and fat. Adipose tissue macrophage infiltration and inflammation were also decreased. PPARgamma response genes were upregulated in adipose tissue from AKO mice and CDK5-mediated PPARgamma ser-273 phosphorylation was reduced, creating a constitutively active PPARgamma state. This identifies NCoR as an adaptor protein that enhances the ability of CDK5 to associate with and phosphorylate PPARgamma. The dominant function of adipocyte NCoR is to transrepress PPARgamma and promote PPARgamma ser 273 phosphorylation, such that NCoR deletion leads to adipogenesis, reduced inflammation, and enhanced systemic insulin sensitivity, phenocopying the TZD treated state. PMID- 22078881 TI - NCoR1 is a conserved physiological modulator of muscle mass and oxidative function. AB - Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARbeta/delta, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function. PMID- 22078882 TI - Systematic discovery of TLR signaling components delineates viral-sensing circuits. AB - Deciphering the signaling networks that underlie normal and disease processes remains a major challenge. Here, we report the discovery of signaling components involved in the Toll-like receptor (TLR) response of immune dendritic cells (DCs), including a previously unkown pathway shared across mammalian antiviral responses. By combining transcriptional profiling, genetic and small-molecule perturbations, and phosphoproteomics, we uncover 35 signaling regulators, including 16 known regulators, involved in TLR signaling. In particular, we find that Polo-like kinases (Plk) 2 and 4 are essential components of antiviral pathways in vitro and in vivo and activate a signaling branch involving a dozen proteins, among which is Tnfaip2, a gene associated with autoimmune diseases but whose role was unknown. Our study illustrates the power of combining systematic measurements and perturbations to elucidate complex signaling circuits and discover potential therapeutic targets. PMID- 22078883 TI - CD14 controls the LPS-induced endocytosis of Toll-like receptor 4. AB - The transport of Toll-like Receptors (TLRs) to various organelles has emerged as an essential means by which innate immunity is regulated. While most of our knowledge is restricted to regulators that promote the transport of newly synthesized receptors, the regulators that control TLR transport after microbial detection remain unknown. Here, we report that the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4. In dendritic cells, this CD14-dependent endocytosis pathway is upregulated upon exposure to inflammatory mediators. We identify the tyrosine kinase Syk and its downstream effector PLCgamma2 as important regulators of TLR4 endocytosis and signaling. These data establish that upon microbial detection, an upstream PRR (CD14) controls the trafficking and signaling functions of a downstream PRR (TLR4). This innate immune trafficking cascade illustrates how pathogen detection systems operate to induce both membrane transport and signal transduction. PMID- 22078884 TI - A network of broadly expressed HLH genes regulates tissue-specific cell fates. AB - Spatial and temporal expression of specific basic-helix-loop-helix (bHLH) transcription factors defines many types of cellular differentiation. We find that a distinct mechanism regulates the much broader expression of the heterodimer partners of these specific factors and impinges on differentiation. In Drosophila, a cross-interacting regulatory network links expression of the E protein Daughterless (Da), which heterodimerizes with bHLH proteins to activate them, with expression of the Id protein Extramacrochaetae (Emc), which antagonizes bHLH proteins. Coupled transcriptional feedback loops maintain the widespread Emc expression that restrains Da expression, opposing bHLH-dependent differentiation while enhancing growth and cell survival. Where extracellular signals repress emc, Da expression can increase. This defines regions of proneural ectoderm independently from the proneural bHLH genes. Similar regulation is found in multiple Drosophila tissues and in mammalian cells and therefore is likely to be a conserved general feature of developmental regulation by HLH proteins. PMID- 22078885 TI - PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. AB - Cells keep their energy balance and avoid oxidative stress by regulating mitochondrial movement, distribution, and clearance. We report here that two Parkinson's disease proteins, the Ser/Thr kinase PINK1 and ubiquitin ligase Parkin, participate in this regulation by arresting mitochondrial movement. PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. Removal of Miro from the mitochondrion also detaches kinesin from its surface. By preventing mitochondrial movement, the PINK1/Parkin pathway may quarantine damaged mitochondria prior to their clearance. PINK1 has been shown to act upstream of Parkin, but the mechanism corresponding to this relationship has not been known. We propose that PINK1 phosphorylation of substrates triggers the subsequent action of Parkin and the proteasome. PMID- 22078886 TI - Regulation of the probability of mouse odorant receptor gene choice. AB - Each olfactory sensory neuron (OSN) in mouse chooses one of 1,200 odorant receptor (OR) genes for expression. OR genes are chosen for expression by greatly varying numbers of OSNs. The mechanisms that regulate the probability of OR gene choice remain unclear. Here, we have applied the NanoString platform of fluorescent barcodes and digital readout to measure RNA levels of 577 OR genes in a single reaction, with probes designed against coding sequences. In an inbred mouse strain with a targeted deletion in the P element, we find that this element regulates OR gene choice differentially across its cluster of 24 OR genes. Importantly, the fold changes of NanoString counts in DeltaP or DeltaH mice are in very close agreement with the fold changes of cell counts, determined by in situ hybridization. Thus, the P and H elements regulate the probability of OR gene choice, not OR transcript level per OSN. PMID- 22078887 TI - The neural circuits and synaptic mechanisms underlying motor initiation in C. elegans. AB - C. elegans is widely used to dissect how neural circuits and genes generate behavior. During locomotion, worms initiate backward movement to change locomotion direction spontaneously or in response to sensory cues; however, the underlying neural circuits are not well defined. We applied a multidisciplinary approach to map neural circuits in freely behaving worms by integrating functional imaging, optogenetic interrogation, genetic manipulation, laser ablation, and electrophysiology. We found that a disinhibitory circuit and a stimulatory circuit together promote initiation of backward movement and that circuitry dynamics is differentially regulated by sensory cues. Both circuits require glutamatergic transmission but depend on distinct glutamate receptors. This dual mode of motor initiation control is found in mammals, suggesting that distantly related organisms with anatomically distinct nervous systems may adopt similar strategies for motor control. Additionally, our studies illustrate how a multidisciplinary approach facilitates dissection of circuit and synaptic mechanisms underlying behavior in a genetic model organism. PMID- 22078888 TI - A mechanism for the evolution of phosphorylation sites. AB - Protein phosphorylation provides a mechanism for the rapid, reversible control of protein function. Phosphorylation adds negative charge to amino acid side chains, and negatively charged amino acids (Asp/Glu) can sometimes mimic the phosphorylated state of a protein. Using a comparative genomics approach, we show that nature also employs this trick in reverse by evolving serine, threonine, and tyrosine phosphorylation sites from Asp/Glu residues. Structures of three proteins where phosphosites evolved from acidic residues (DNA topoisomerase II, enolase, and C-Raf) show that the relevant acidic residues are present in salt bridges with conserved basic residues, and that phosphorylation has the potential to conditionally restore the salt bridges. The evolution of phosphorylation sites from glutamate and aspartate provides a rationale for why phosphorylation sometimes activates proteins, and helps explain the origins of this important and complex process. PMID- 22078889 TI - SnapShot: Mitochondrial quality control. PMID- 22078890 TI - Coffers brimming, ethically bankrupt. PMID- 22078894 TI - [36th Congress of the French Maxillo-Facial Association (AFCMF), La Pedrera, Barcelona, Spain]. PMID- 22078891 TI - Successful treatment of activated occult hepatitis B in a non-responder chronic hepatitis C patient. AB - We reported a 23 years old male with chronic hepatitis C virus infection, discontinued from pegylated interferon/ribavirin combination therapy due to a lack of early virological response. He has developed activation of occult hepatitis B virus that was successfully treated by a one year of lamivudine therapy. PMID- 22078895 TI - [Stability of Le Fort I impaction osteotomies]. AB - INTRODUCTION: Long-term results of Le Fort I osteotomy with vertical impaction for maxillary vertical excess may be not stable. We had for aim to analyze postoperative maxillary and dental displacement after a Le Fort I vertical impaction osteotomy, to identify causes of relapse. PATIENTS AND METHODS: A clinical and radiological evaluation was made on postoperative occlusion (early and late). The position of three bone (O: lower orbit; P: greatest palatine convexity; T: lowest part of the mandibular foramen) and of three dental landmarks (I: occlusal edge of the upper incisor; i: occlusal edge of the lower incisor; m: first molar distal vestibular cuspid) was measured in a standardized method on pre-surgical, early and late (1 to 2.5 years) postoperative cephalometric X rays. Eighteen patients were operated by the same surgeon for maxillary anterior vertical excess and underwent Le Fort I impaction osteotomy, alone or associated with a mandibular osteotomy. Stability was defined by a postoperatory displacement smaller than 1mm. RESULTS: All patients had stable bone landmarks. Three patients had unstable dental landmarks due to relapse. DISCUSSION: Impaction maxillary osteotomy provides stable bone results for maxillary facial height excess. Unsatisfactory outcome is always due to postoperative dental and alveolar displacement. These results correlate to published data. PMID- 22078896 TI - [A giant radiolucent maxillary lesion]. PMID- 22078897 TI - [Identity and facial graft]. PMID- 22078898 TI - [Maxillary sinus septa. Prevalence and anatomy]. AB - BACKGROUND: Maxillary sinus septa may complicate sinus elevation procedures, especially when they are not diagnosed prior to surgery. The authors had for aim to review published data, to analyze the etiology, the prevalence, the localization, and the size of maxillary sinus septa, and to determine what were the best preoperative radiological examinations. PATIENTS AND METHODS: The Medline search was made with keywords such as "maxillary sinus anatomy, maxillary sinus augmentation, maxillary sinus septa, sinus graft/complications, dental implants". The search was limited to studies published in English from 1980 to January 2009. RESULTS: Twenty-two articles were analyzed. The prevalence of maxillary sinus septa ranged between 14.3% and 33.3%. There was no specific geographic distribution within the sinuses. The mean heights of septa ranged between 2.8 and 8.1 mm. DISCUSSION: It is recommended to systematically use preoperative CT or CBCT scan imaging because of the prevalence, the variable anatomy, and the bad contribution of conventional X-rays. PMID- 22078899 TI - [Severe vascular complications of Le Fort I osteotomy]. AB - INTRODUCTION: Le Fort I osteotomy is a common orthognathic procedure. This surgery presents risk of severe vascular complications because of local anatomy. The aim of our study was to collect data on vascular complications of Le Fort I osteotomies performed in our department, describe the diagnostic and therapeutic aspects, and discuss prevention. PATIENTS AND METHODS: A retrospective analysis was made on the files of patient having undergone Le Fort 1 osteotomy, between 1998 and 2007. Severe vascular complications were recorded, defined as postoperative hemorrhagic or ischemic complications severe enough to require a specific procedure. RESULTS: Nine hundred and sixteen patient files were included (39% male and 61% female patients, mean-age: 24.42 years; range: 13 to 59 years). Five patients presented with severe hemorrhagic complication. There was no ischemic complication. Three hemorrhagic episodes occurred in the immediate postoperative phase. In two cases, delayed hemorrhagic complication occurred, diagnosed as a pseudo-aneurysm by angiography. These were treated by hyperselective embolization. DISCUSSION: Vascular complications of Le Fort I osteotomies are rare (0.55% in our series). They are most frequently hemorrhagic complications. PMID- 22078900 TI - Weighing in on risk factors for body dissatisfaction: a one-year prospective study of middle-adolescent girls. AB - Body dissatisfaction is a common problem among adolescent girls that is linked to serious outcomes, including the development of eating disorders. This study tested to what degree five theorized risk factors (weight-related teasing, thin ideal internalization, body mass index [BMI], self-esteem, and perfectionism) predicted prospective changes in body dissatisfaction. At baseline, 393 10th and 11th grade girls (M=15.8 years) completed questionnaires and had their height and weight measured. One year later, 316 participants' body dissatisfaction was reassessed (80.4% retention). Results suggested that self-esteem was the most potent risk factor, followed by BMI, when used to categorize girls into high- and low-risk groups for body dissatisfaction at follow-up. However, weight-related teasing, thin-ideal internalization, and perfectionism did not prove to be risk factors. These results suggest self-esteem and BMI are relevant variables for helping to identify middle-adolescent girls who may be at risk for subsequent increases in body dissatisfaction. PMID- 22078901 TI - Choice of analytic approach for eye-specific outcomes: one eye or two? AB - PURPOSE: To investigate the use of analytic approaches for eye-specific outcomes in ophthalmology publications. DESIGN: A review of analytic approaches used in original research articles published in ophthalmology journals. METHODS: All 161 research articles published in 5 ophthalmology journals in the first 2 months of 2008 were considered. Publications were categorized according to analytic approach: 1 eye selected, both eyes contribute, or per-individual outcome. Studies were considered suboptimal when criteria for eye selection were not provided or when measurements from both eyes were included without interocular correlation being considered. Visual impairment prevalence data were used to illustrate analytic approach choices. RESULTS: Measurements from both eyes were included in 38% of the 112 studies that used statistical inferential techniques. In 31 (74%), there was no mention of possible correlation. Only 7% used statistical methods appropriate for correlated outcomes. In 35 studies (31%), measurements from 1 eye were selected; 31% of these did not provide selection criteria. In 67%, only univariate tests were used. A review of 47 articles published in 2011 produced similar findings. Characteristics of studies were not found to differ according whether the studies were suboptimal. Using a test appropriate for correlated outcomes resulted in a P value 3.5 times that obtained ignoring the correlation. CONCLUSIONS: Between-eye correlation seems not to be assessed commonly in ophthalmology publications, although its knowledge aids the choice of analytic approach when eye-specific variables are of interest. Statistical methods appropriate for correlated ocular outcome data are not being applied widely. PMID- 22078902 TI - Combined intravitreal ranibizumab and photodynamic therapy for retinal angiomatous proliferation. AB - PURPOSE: To clarify the efficacy of combined therapy with intravitreal ranibizumab injections and photodynamic therapy (PDT) in patients with symptomatic retinal angiomatous proliferation. DESIGN: Retrospective, interventional, consecutive case series. METHODS: We retrospectively reviewed 20 treatment-naive eyes of 16 patients (8 men, 8 women; age range, 79 to 92 years; mean age, 84.8 years) treated with 3 consecutive monthly intravitreal injections of ranibizumab (0.5 mg/0.05 mL) and PDT and followed up for at least 12 months. PDT was applied 1 or 2 days after the initial injection. Retreatment was performed as a combined therapy of a single intravitreal ranibizumab injection and PDT. RESULTS: The mean best-corrected visual acuity (BCVA) levels significantly improved from 0.24 at baseline to 0.43 at 12 months (P < .001). The mean improvement in BCVA at 12 months from baseline was 2.51 lines. The BCVA at 12 months improved in 10 eyes (improved by 3 lines or more) and was stable (defined as a loss of less than 3 lines of vision) in 10 eyes. No patient had a decrease in the BCVA of 3 lines or more during any 12 months. The central retinal thickness decreased significantly from 444 MUm at baseline to 143 MUm at 12 months (P < .0001). Complete occlusion of the retinal-retinal anastomosis was achieved in 17 of the 19 eyes at 12 months. The mean numbers of PDT treatments and injections during 12 months, including the treatments in the initial regimen, were 1.8 and 3.8, respectively. No complications or systemic adverse events developed. CONCLUSIONS: Combined intravitreal ranibizumab and PDT for patients with retinal angiomatous proliferation effectively maintained or improved visual acuity and reduced the exudation without adverse events. PMID- 22078903 TI - Molecular characterization of drug-resistant and -susceptible Mycobacterium tuberculosis isolated from patients with tuberculosis in Korea. AB - We investigated the causal relationship between genotype and phenotype of drug resistant Mycobacterium tuberculosis isolates obtained from patients with pulmonary tuberculosis (TB) in Korea. Of 80 isolates tested, 17, 20, 1, and 7 isolates were mono-resistant to ethambutol (EMB), isoniazid (INH), pyrazinamide (PZA), and rifampicin (RFP), respectively, and 31 isolates (38.8%) were multidrug resistant (MDR). Sequencing analysis showed that 78% (32/41) of RFP-resistant strains had mutations in the rifampicin resistance-determining region (RRDR) of rpoB, and the mutation at rpoB531 (59.4%) was most abundant. In 52 INH-resistant strains, mutations were found mostly at C-15T (n = 21, 40.4%) in the inhA promoter region as well as at katG315 (n = 12, 23.1%). Mutations at embB306 were mostly found in 26.7% (12/45) of EMB-resistant isolates. New mutations found here in MDR isolates include rpoB523 (Gly523Glu) and embB319 (Tyr319Ser). Consequently, mutations in the rpoB531, C-15T in the inhA promoter region, embB306, and katG315 would be a useful marker for rapid detection of MDR M. tuberculosis isolates in Korea. PMID- 22078904 TI - Detection and discrimination of Mycobacterium tuberculosis complex. AB - A real-time quantitative polymerase chain reaction (qPCR) was developed for detection and discrimination of Mycobacterium tuberculosis (H37Rv and H37Ra) and M. bovis bacillus Calmette-Guerin (BCG) of the Mycobacterium tuberculosis complex (MTBC) from mycobacterial other than tuberculosis (MOTT). It was based on the melting curve (Tm) analysis of the gyrB gene using SYBR((r)) Green I detection dye and the LightCycler 1.5 system. The optimal conditions for the assay were 0.25 MUmol/L of primers with 3.1 mmol/L of MgCl(2) and 45 cycles of amplification. For M. tuberculosis (H37Rv and H37Ra) and M. bovis BCG of the MTBC, we detected the crossing points (Cp) at cycles of 16.96 +/- 0.07, 18.02 +/- 0.14, and 18.62 +/- 0.09, respectively, while the Tm values were 90.19 +/- 0.06 degrees C, 90.27 +/- 0.09 degrees C, and 89.81 +/- 0.04 degrees C, respectively. The assay was sensitive and rapid with a detection limit of 10 pg of the DNA template within 35 min. In this study, the Tm analysis of the qPCR assay was applied for the detection and discrimination of MTBC from MOTT. PMID- 22078905 TI - Detection and quantification of the K103N mutation in HIV reverse transcriptase by pyrosequencing. AB - Prolonged treatment of human immunodeficiency virus (HIV)-infected patients with nonnucleoside reverse transcriptase inhibitors (NNRTIs) might result in the selection of resistant mutants, the most frequent being the K103N mutation in reverse transcriptase. Resistance mutations are routinely detected by Sanger sequencing of the whole viral population, which does not detect sequence variants with frequencies below 20%. We have developed a pyrosequencing approach for the analysis of codon 103 of the HIV reverse transcriptase gene in the circulating viral population that detects variants below the limit of conventional sequencing. The method was tested with samples from 5 controls (not exposed to NNRTIs), 6 from patients exposed to NNRTIs and having a K103N mutant virus population detected by conventional sequencing, and 9 from patients previously exposed to NNRTIs that had a wild-type virus population by conventional sequencing. In 7 of 9, samples the mutation could not be detected by either the standard assay or pyrosequencing, while in 2 samples persistence of the mutation could be detected by pyrosequencing. The method might be of practical use in detecting minority variants of HIV in the clinical setting, in epidemiological studies with large numbers of samples, or as a complement to more complex approaches. PMID- 22078906 TI - Emergence in Japan of an imipenem-susceptible, meropenem-resistant Klebsiella pneumoniae carrying blaIMP-6. AB - We identified 5 Klebsiella pneumoniae isolates showing high resistance to beta lactams except imipenem and designated them ISMRK (imipenem-susceptible but meropenem-resistant Klebsiella). They carried the bla(IMP-6) and bla(CTX-M-2) on a self-transmissible plasmid. ISMRK may be falsely categorized as susceptible to carbapenems if imipenem is used to screen carbapenem resistance. PMID- 22078907 TI - Molecular characterization of group G Streptococcus dysgalactiae subsp. equisimilis recovered from patients and healthy people in China. AB - Beta-Hemolytic group G streptococci cause a considerable invasive disease burden and sometimes disease outbreaks. Little is known about the critical epidemiologic parameter of genetic relatedness between isolates. We determined the emm types of 65 Streptococcus dysgalactiae subsp. equisimilis isolates. We formulated multilocus sequence typing (MLST) primers with 6 of the 7 loci corresponding to the Streptococcus pyogenes MLST scheme. We performed MLST with 69 S. dysgalactiae subsp. equisimilis isolates to represent each emm type identified. These strains were further analyzed by pulsed-field gel electrophoresis (PFGE) typing. Sixteen emm types were observed. Eighteen unique combinations of allelic profiles (sequence types [STs]) were obtained with 12 profiles each accounting for multiple isolates. Forty-one MLST STs were observed. Analysis of the PFGE patterns generated revealed 10 clones. Over 80% of the isolates were distributed in 3 large clones. Isolates within 16 redundantly represented S. dysgalactiae subsp. equisimilis emm types shared identical or nearly identical STs and subtypes of PFGE, demonstrating concordance between the emm type and genetic relatedness. It is conceivable that some particular characteristics in the genomes of these strains are responsible for their predominance in different regions. PMID- 22078908 TI - Molecular diagnosis and species identification of imported malaria in returning travellers in Italy. AB - A new seminested polymerase chain reaction (sn-PCR)-based protocol was developed and used to detect and identify Plasmodium species in 1226 whole-blood samples from patients (872 Italians and 354 foreigners) with at least 1 symptom compatible with clinical malaria. The results were compared with those obtained by microscopy: 187 samples were positive by microscopy for malaria parasites and 196 were positive by sn-PCR. When compared to microscopy, the sn-PCR detected different malaria parasite species in 11 cases. In 4 of 11 cases, the sn-PCR identified 1 additional malaria parasite species not observed microscopically, suggesting increased sensitivity. In 4 samples with levels of parasitemia too low for accurate identification of species by microscopy, the sn-PCR detected 2 P. falciparum, 1 P. ovale, and 1 P. falciparum plus P. ovale. Moreover, 9 negative samples by microscopy were positive by sn-PCR. Follow-up analysis demonstrated a parasite clearance of P. falciparum DNA up to 3 days after the disappearance of parasitemia at microscopy. In conclusion, sn-PCR-based diagnosis of malaria appears to be a useful tool when the results of conventional techniques are negative in the presence of a syndrome consistent with malaria, yielding accurate species identification and consequential correct treatment. PMID- 22078909 TI - Telavancin activity tested against a contemporary collection of Gram-positive pathogens from USA Hospitals (2007-2009). AB - This study updates the activity of telavancin against Gram-positive pathogens collected from USA hospitals (2007-2009). Telavancin (MIC(50/90), 0.12/0.25 MUg/mL) was active against coagulase-negative staphylococci and methicillin resistant Staphylococcus aureus (100% susceptible), for which only daptomycin (MIC(50/90), 0.25/0.5 MUg/mL; 99% susceptible) and quinupristin/dalfopristin (MIC(50/90), <= 0.25-0.5/0.5 MUg/mL; 99% susceptible) exhibited similar activity. Telavancin (MIC(50/90), 0.25/0.5 MUg/mL) inhibited 96.5% of Enterococcus faecalis at the Food and Drug Administration breakpoint (MIC, <= 1 MUg/mL), where ampicillin (99.9% susceptible), daptomycin (99.9% susceptible), and linezolid (100% susceptible) also demonstrated high-level coverage. Telavancin inhibited, respectively, 100.0% and 91.7% of VanB-phenotype E. faecalis and E. faecium at <= 1 MUg/mL, whereas it was less active against VanA strains. Telavancin was uniformly active against Streptococcus pneumoniae and resistant subsets, and demonstrated good potency (MIC(90), 0.06-0.12 MUg/mL) against other streptococci, regardless of resistance to other drugs. This assessment reveals potent activity of telavancin against Gram-positive isolates collected from USA hospitals with no evidence of emergence of resistance. PMID- 22078910 TI - Pharmacology of commonly used analgesics and sedatives in the ICU: benzodiazepines, propofol, and opioids. AB - The ideal sedative or analgesic agent should have a rapid onset of activity, a rapid recovery after drug discontinuation, a predictable dose response, a lack of drug accumulation,and no toxicity. Unfortunately, none of the earlier analgesics, the benzodiazepines,or propofol share all of these characteristics. Patients who are critically ill experience numerous physiologic derangements and commonly require high doses and long durations of analgesic and sedative therapy. There is a paucity of well designed clinical trials evaluating the safety and efficacy of earlier sedative and analgesic agents in the ICU. In addition, the ever-changing dynamics of patients who are critically ill makes the use of sedation a continual challenge during the course of each patient's admission. To optimize care, clinicians should be familiar with the many pharmacokinetic, pharmacodynamic, and pharmacogenetic variables that can affect the safety and efficacy of sedatives and analgesics. PMID- 22078911 TI - Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral Mu antagonists. AB - In this article, the authors discuss the pharmacology of sedative-analgesic agents like dexmedetomidine, remifentanil, ketamine, and volatile anesthetics. Dexmedetomidine is a highly selective alpha-2 agonist that provides anxiolysis and cooperative sedation without respiratory depression. It has organ protective effects against ischemic and hypoxic injury, including cardioprotection, neuroprotection, and renoprotection. Remifentanil is an ultra-short-acting opioid that acts as a mu-receptor agonist. Ketamine is a nonbarbiturate phencyclidine derivative and provides analgesia and apparent anesthesia with relative hemodynamic stability. Volatile anesthetics such as isoflurane, sevoflurane, and desflurane are in daily use in the operating room in the delivery of general anesthesia. A major advantage of these halogenated ethers is their quick onset, quick offset, and ease of titration in rendering the patient unconscious, immobile, and amnestic. PMID- 22078912 TI - Current sedation practices: lessons learned from international surveys. AB - Limitations are inherent to surveys. Most surveys have low response rates, which raises the issue of responder bias. Another limitation of self-report surveys stems from the possible differences between stated and actual practice. That is, what physicians report that they do in surveys often contrasts significantly with what they do in observational studies, as highlighted by the Canadian surveys conducted in 2002 and 2008. Some surveys report estimates provided by ICU nurse managers or physician directors, potentially resulting in inaccurate estimates or data reflecting the individuals practice rather than the entire ICU. Surveys may not reflect how different specialists practice; for example, the German surveys collected data only in ICUs run by anesthesiologists.Notwithstanding these limitations, surveys provide a wealth of information on current practice and determinants of practice, and serve as a useful tool to guide future research and educational interventions. The authors identified substantial international variation in the use of sedative and analgesic drugs, and marked changes over the last 10 years. Overall, there is a trend toward lighter sedation, along with a shift from benzodiazepines toward propofol, and from morphine toward fentanyl and remifentanil. Despite the publication of numerous studies and guidelines for sedation and analgesia, actual practice differs from recommended practice, suggesting that the impact of clinical trials and guidelines on physician practice is quite low. It is clear that there remain substantial barriers to the incorporation of sedation scales, protocols,and daily interruption into routine ICU care. PMID- 22078913 TI - Protocolized and target-based sedation and analgesia in the ICU. AB - Protocolized target-based sedation and analgesia is central to effective management of sedation. Important components include identifying goals and specific targets,using valid and reliable tools to measure pain, agitation, and sedation, and titrating a logically selected combination of sedatives and analgesics to defined end-points.A variety of approaches to structured management have been tested in controlled trials with major categories of (1) sedation algorithms and protocols and (2) daily interruption of sedation. Although not all studies that compare new interventions to "usual care" document dramatic improvements, many studies show that by reducing oversedation, using a structured approach, faster recovery from respiratory failure may ensue. The somewhat discrepant results illustrate, however, that various approaches,such as DIS, may not be optimal for all patients. Further research will be necessary to define these patients and examine alternative strategies. Finally, implementation of structured approaches to sedation management is a challenging, time-consuming process for clinicians that must be supported with sufficient resources to be successful. PMID- 22078914 TI - Sedation and weaning from mechanical ventilation: linking spontaneous awakening trials and spontaneous breathing trials to improve patient outcomes. AB - The use of sedation has long been integrated into critical care. Because pain, discomfort, anxiety, and agitation are commonly experienced by critically ill patients, the use of medications to alleviate and control these symptoms will continue; however, data showing that prolonged use of sedating medications imparts harm to patients obligate physicians to use agents and methods of sedation that minimize these negative side effects. Numerous observational studies and clinical trials have proven that decisions in sedation management play a crucial role in determining outcomes for mechanically ventilated ICU patients, and recent evidence supports the use of protocols that streamline efforts to discontinue sedation and mechanical ventilation in a safe and parallel fashion. Regardless of choice of sedating agent, and even when patient-targeted sedation protocols are used to minimize oversedation, the use of spontaneous awakening trials dramatically improves patient outcomes for critically ill patients. Intensive care physicians must continue to study the delivery of sedation in efforts to maximize patient comfort while minimizing patient harm. PMID- 22078915 TI - Altering intensive care sedation paradigms to improve patient outcomes. AB - Providing sedation and comfort for intensive care patients has evolved in the last 30 years but remains difficult for clinicians. As research has focused on this challenging area, the authors have identified ways to improve practice, including providing analgesia before sedation, strategies to help recognize dangerous adverse effects associated with the medications that are used, and better ways to monitor pain and delirium in patients. Dexmedetomidine and propofol have become the preferred sedatives for many ICU situations, and creative ways to administer them, such as linking awakening and breathing trials, are emerging. Finally, screening survivors for cognitive impairments may allow clinicians to refer them for the focused rehabilitation they require. PMID- 22078916 TI - Sedation and sleep disturbances in the ICU. AB - Sedation in the ICU is, paradoxically, both a cause and a potential treatment for the sleep disruption almost universally observed in the critically ill. A patient focused sedation strategy that minimizes unnecessary medication, avoids medication withdrawal, addresses the specific impediments to sleep, and serves as an adjunct to attentive environmental control may ultimately serve patients best. PMID- 22078917 TI - Sedation & immunomodulation. AB - As the armamentarium for sedation in the critically ill expands, opportunities will develop to modulate the immune responses of patients by way of the direct immune and neural-immune interactions of the sedatives. Control of autonomic activity through the use of appropriate sedation may be critical in this matter. Likewise analgesic-based sedation, with increased opioid dosage, may not prove beneficial in the setting of infection; whether avoidance of morphine in preference for a fentanyl derivative will help is unclear. However, as the immune effects seem dependent on the m receptor, it is improbable that a significant difference would be uncovered. Similarly, the present evidence suggests benzodiazepines are deleterious in infection; further studies are required urgently to evaluate this evidence. As an alternative to benzodiazepine-based sedation, dexmedetomidine has shown a remarkable 70% mortality benefit in a small secondary analysis of septic patients from the MENDS trial. Further powered clinical studies should now be undertaken to investigate the potential benefit of the alpha2-adrenoceptor agonist in this setting, with comparisons with propofol. PMID- 22078918 TI - Pharmacoeconomics of sedation in the ICU. AB - Despite considerable information on the pharmacotherapy of sedation in the ICU, there is little published on the pharmacoeconomics of sedation in patients who are critically ill. The purpose of this article is to discuss the various components that contribute to the cost of treating the agitated ICU patient and to critically review the articles published since 2000 that evaluated costs and cost-effectiveness in ICU patients receiving drugs for agitation and/or pain. Clinicians should look beyond the acquisition cost of a sedative and include the effect of sedatives on the cost of care when selecting the most appropriate sedative. PMID- 22078919 TI - Delirium prevention and treatment. AB - Little is known of nonpharmacologic and pharmacologic delirium prevention and treatment in the critical care setting. Trials emphasizing early mobilization suggest that this nonpharmacologic approach is associated with an improvement in delirium incidence. Titration and reduction of opiate analgesics and sedatives may improve subsyndromal delirium rates. All critical care caregivers should rigorously screen for alcohol abuse, apply alcohol withdrawal scales in alcoholic patients, and titrate sedative drugs accordingly. No nonpharmacologic approach or drug has been shown to be beneficial once delirium is established. Considering the importance and the consequences of delirium in the critical care setting, studies to further address prevention and rigorous trials addressing pharmacologic intervention are urgently needed. PMID- 22078920 TI - Delirium: an emerging frontier in the management of critically ill children. AB - Delirium is a syndrome of acute brain dysfunction that commonly occurs in critically ill adults and most certainly is prevalent in critically ill children all over the world. The dearth of information about the incidence, prevalence, and severity of pediatric delirium stems from the simple fact that there have not been well-validated instruments for routine delirium diagnosis at the bedside. This article reviewed the emerging solutions to this problem, including description of a new pediatric tool called the pCAM-ICU. In adults, delirium is responsible for significant increases in both morbidity and mortality in critically ill patients. The advent of new tools for use in critically ill children will allow the epidemiology of this form of acute brain dysfunction to be studied adequately, will allow clinical management algorithms to be developed and implemented following testing, and will present the necessary incorporation of delirium as an outcome measure for future clinical trials in pediatric critical care medicine. PMID- 22078921 TI - Cognitive functioning, mental health, and quality of life in ICU survivors: an overview. AB - The significant and sometimes permanent effects of critical illness on wide ranging aspects of functioning are increasingly recognized. Among the areas affected are acute and long-term cognitive functioning, depression, anxiety, PTSD, and quality of life. These and other areas are increasingly being studied and indeed are increasingly the focus of clinical attention and investigations. These conditions have been a focus of attention for more than a dozen years, with much improvement occurring in the ability to characterize these phenomena. For instance, in intervening years, it has been learned that cognitive impairment is highly prevalent and functionally disruptive and that it occurs in wide-ranging domains. Key questions remain unanswered with regard to vital questions such as determining causes, risk factors, and mechanisms as well as the degree to which brain injuries associated with critical illness are amenable to rehabilitation. Little remains known about the effects of critical illness on elderly ICU cohorts and on the neurologic functioning of individuals with preexisting impairment versus those who are normal. Few data exist regarding the development of strategies designed to prevent the emergence of neuropsychological deficits after critical illness. Although great progress has been made and is ongoing, a pressing need exists for additional investigation of cognitive impairment and other conditions,such as PTSD and quality of life after critical illness, that will seek to untangle the many pertinent questions related to this condition and that will ultimately offer help and hope to the thousands of survivors affected by this condition. PMID- 22078923 TI - Sedation and analgesia in the ICU: pharmacology, protocolization, and clinical consequences. Preface. PMID- 22078924 TI - Surface charging and dimensions of chitosan coacervated nanoparticles. AB - Chitosan nanoparticles have been used in several systems destined to controlled release of active agents. In this manuscript the process of formation of chitosan nanoparticles, obtained employing the coacervation method with sodium sulfate is analyzed using zeta potential and small angle X-ray scattering (SAXS) measurements. Dispersions were obtained at pH=1 and pH=3 and presented a behavior, in terms of surface charging, that was independent of pH. However, SAXS results indicated a dependence of size-related behavior on pH. The difference in terms of behavior was explained through the influence of enthalpic and entropically driven components. PMID- 22078925 TI - Polyelectrolyte multilayer capsules with quantum dots for biomedical applications. AB - The aim of this work was to encapsulate the CdTe quantum dots within the nanocapsules that were prepared by the layer-by-layer adsorption of polyelectrolytes. Two different polyelectrolyte pairs were used as components of the shell: synthetic polycation poly(allyamine hydrochloride) (PAH), together with anionic poly(sodium styrene sulfonate) (PSS), and biocompatible cationic poly-L-lysine hydrobromide in a pair with biocompatible anionic poly-D-glutamic acid sodium salt (PGA). The saturation method was used for formation of consecutive layers on the initial CdTe-polyelectrolyte complex. A growth of the polyelectrolyte shell was followed with the electrophoretic mobility and light scattering measurements, in order to determine the zeta potential and the size of capsules, respectively. The fluorescent spectra of the quantum dots, which are embedded within the capsules, were characterized with spectrofluorimeter. Later on, they were deposited on a negatively charged mica surface and studied by the means of atomic force microscopy (AFM). In order to estimate the cytotoxicity of capsules, their influence on the B-lymphoblastoid cell line proliferation and on unspecific binding to the P-blood mononuclear cells was examined using the flow cytometry. PMID- 22078926 TI - The phenotypic response of bovine corneal endothelial cells on chitosan/polycaprolactone blends. AB - Although various behaviors of corneal endothelial cells (CECs) have been investigated, the interaction of CECs with different biodegradable biomaterials has not been systematically well explored. Thus, two common biodegradable biomaterials with dissimilar characteristics, chitosan and polycaprolactone (PCL), were examined in bovine CEC (BCEC) culture systems to elucidate their possible impact on clinical demand and scientific interest. The interaction between cells and matrices was also surveyed. Pure PCL could not be used for observation because of its opacity. Nevertheless, BCECs did not adhere and proliferate well on chitosan. To overcome this drawback, we developed blends using various proportions of chitosan and PCL: PCL 25, PCL 50, and PCL 75. As the content of PCL increased in the blends, BCECs showed greater degrees of adhesion and proliferation. Furthermore, cells reached confluence and maintained their typical hexagonal shape at day 7 on blends PCL 50 and PCL 75. In addition, when BCECs were cultured on the blends, the expressions of the differentiation marker N-cadherin and tight junction marker ZO-1 were well developed, resembling the physiological phenotypes. A possible explanation for the increased proliferation and preservation of BCECs on the blends is that blending chitosan and PCL could create a bioactive substratum. This method could regulate gene expression to synthesize more extracellular matrix type IV collagen, paving an important way to provide a favorable environment for BCEC cultures. Accordingly, promoting CEC growth effects by blending may be applied to the tissue engineering of corneal endothelium. PMID- 22078928 TI - Synthesis of glucose-responsive bioconjugated gel particles using surfactant-free emulsion polymerization. AB - Bioconjugated gel particles that have complexes composed of lectin concanavalin A (ConA) and 2-glucosyloxyethyl methacrylate (GEMA) were synthesized by the surfactant-free emulsion copolymerization of N,N-diethylaminoethyl methacrylate (DEAEMA), poly(ethylene glycol) dimethacrylate (PEGDMA), GEMA, and modified-ConA with polymerizable groups. The resultant gel particles having GEMA-ConA complexes (GEMA-ConA gel particles) were colloidally stable in a phosphate buffer solution and had a diameter of approximately 750nm. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) measurements implied that GEMA-ConA gel particles have core-shell structures consisting of a hydrophobic core of DEAEMA and a hydrophilic shell of GEMA and PEGDMA containing ConA. GEMA-ConA gel particles underwent a change in size in response to glucose in a phosphate buffer solution. The swelling ratio of GEMA-ConA gel particles gradually increased with an increase in the glucose concentration. On the other hand, the swelling ratio of GEMA-ConA gel particles remained unchanged in a phosphate buffer solution containing galactose. The glucose-responsive swelling of GEMA-ConA gel particles was induced by the dissociation of GEMA-ConA complexes acting as reversible cross-links, because free glucose behaved as an inhibitor of GEMA-ConA complexes. These results indicate that GEMA-ConA gel particles can recognize glucose selectively and undergo changes in size in response to the glucose concentration. The smart functions of glucose-responsive gel particles can provide tools for constructing self-regulated drug delivery systems and sensor systems useful for treating diabetes. PMID- 22078927 TI - Cancer nanomedicines targeting tumor extracellular pH. AB - Tumors have been a highlight in the research of nanomedicine for decades. Despite all the efforts in the decoration of the nano systems, tumor specific targeting is still an issue due to the heterogeneous nature of tumors. Hypoxia is frequently observed in solid tumors. The consequent acidification of tumor extracellular matrices may bring new insight to tumor targeting. In this review, we present the polymeric nano systems that target tumor extracellular pH (pH(e)). PMID- 22078929 TI - Perceptual consciousness overflows cognitive access. AB - One of the most important issues concerning the foundations of conscious perception centers on the question of whether perceptual consciousness is rich or sparse. The overflow argument uses a form of 'iconic memory' to argue that perceptual consciousness is richer (i.e., has a higher capacity) than cognitive access: when observing a complex scene we are conscious of more than we can report or think about. Recently, the overflow argument has been challenged both empirically and conceptually. This paper reviews the controversy, arguing that proponents of sparse perception are committed to the postulation of (i) a peculiar kind of generic conscious representation that has no independent rationale and (ii) an unmotivated form of unconscious representation that in some cases conflicts with what we know about unconscious representation. PMID- 22078930 TI - Cortical electrophysiological network dynamics of feedback learning. AB - Understanding the neurophysiological mechanisms of learning is important for both fundamental and clinical neuroscience. We present a neurophysiologically inspired framework for understanding cortical mechanisms of feedback-guided learning. This framework is based on dynamic changes in systems-level oscillatory synchronization, reflecting changes in synaptic plasticity between stimulus processing and motor areas that are modulated in a top-down fashion by different areas of the prefrontal cortex. We make new and testable predictions for how large-scale cortical networks support learning from feedback. Testing these predictions may provide new insights into the basic mechanisms underlying learning and how these mechanisms may be impaired in clinical disorders in which feedback learning is compromised. PMID- 22078931 TI - Psychobiological allostasis: resistance, resilience and vulnerability. AB - The brain and body need to adapt constantly to changing social and physical environments. A key mechanism for this adaptation is the 'stress response', which is necessary and not negative in and of itself. The term 'stress', however, is ambiguous and has acquired negative connotations. We argue that the concept of allostasis can be used instead to describe the mechanisms employed to achieve stability of homeostatic systems through active intervention (adaptive plasticity). In the context of allostasis, resilience denotes the ability of an organism to respond to stressors in the environment by means of the appropriate engagement and efficient termination of allostatic responses. In this review, we discuss the neurobiological and organismal factors that modulate resilience, such as growth factors, chaperone molecules and circadian rhythms, and highlight its consequences for cognition and behavior. PMID- 22078932 TI - Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure. AB - PURPOSE: This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib. MATERIALS AND METHODS: This open-label, multicentre, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function. The primary end-point was objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) by central imaging. Secondary end-points were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). Safety was also assessed. RESULTS: Fifty-three patients, median age 61 years (range 40-80) were enrolled (August 2007 to October 2008) across 12 North-American centres. Median number of prior therapies was 2 (range 1-4); 43 patients (81%) had clear-cell histology. ORR was 13.2%, median PFS was 5.4 months (95% Confidence Interval (CI): 3.6, 6.0) and TTP was the same; median OS was 14.5 months (95% CI: 10.8, 24.1). The most common treatment-related adverse events (AEs) were diarrhoea (74%), fatigue (74%) and hypertension (66%), and the most common treatment-related Grade 3/4 AE was hypertension (40%). CONCLUSIONS: Linifanib demonstrated clinically meaningful activity in patients with advanced RCC after sunitinib failure. At 0.25 mg/kg/day, significant dose modifications were required. An alternative, fixed-dosing strategy is being evaluated in other trials. PMID- 22078934 TI - Comment on: Outcome of laparoscopic adjustable gastric banding and the prevalence of band revision and explantation at academic centers: 2007-2009. PMID- 22078933 TI - Proatherogenic abnormalities of lipid metabolism in SirT1 transgenic mice are mediated through Creb deacetylation. AB - Dyslipidemia and atherosclerosis are associated with reduced insulin sensitivity and diabetes, but the mechanism is unclear. Gain of function of the gene encoding deacetylase SirT1 improves insulin sensitivity and could be expected to protect against lipid abnormalities. Surprisingly, when transgenic mice overexpressing SirT1 (SirBACO) are placed on atherogenic diet, they maintain better glucose homeostasis, but develop worse lipid profiles and larger atherosclerotic lesions than controls. We show that transcription factor cAMP response element binding protein (Creb) is deacetylated in SirBACO mice. We identify Lys136 is a substrate for SirT1-dependent deacetylation that affects Creb activity by preventing its cAMP-dependent phosphorylation, leading to reduced expression of glucogenic genes and promoting hepatic lipid accumulation and secretion. Expression of constitutively acetylated Creb (K136Q) in SirBACO mice mimics Creb activation and abolishes the dyslipidemic and insulin-sensitizing effects of SirT1 gain of function. We propose that SirT1-dependent Creb deacetylation regulates the balance between glucose and lipid metabolism, integrating fasting signals. PMID- 22078935 TI - Interim results at 48 weeks of LAP-BAND AP experience (APEX) study: prospective, multicenter, open-label longitudinal patient observational study. AB - BACKGROUND: The development of laparoscopic adjustable gastric banding marked a breakthrough in minimally invasive bariatric surgery. The unique features of gastric banding, including device adjustability, lack of malabsorption, and easy reversibility, have contributed to its widespread use. Since Food and Drug Administration approval of the first laparoscopic adjustable gastric band, the device design has undergone engineering improvements. The LAP-BAND AP (LBAP) system received Food and Drug Administration approval in 2006. Little is known about the safety and efficacy of this new system. Our objective was to prospectively assess the efficacy and safety of the LBAP system in real-world clinical settings at 50 clinical centers throughout the United States. METHODS: In an open-label 5-year evaluation, 508 severely or morbidly obese patients from 50 centers in the United States underwent surgery using the LBAP system. The present interim report describes the results from 323 patients after >= 48 weeks of follow-up. RESULTS: By week 48, the patients had experienced a mean percentage of excess weight loss of 46% and a mean +/- standard deviation reduction in the body mass index of 8.4 +/- 3.69 kg/m(2). Sixteen patients (3.1%) experienced a severe device- or procedure-related adverse event. There were no deaths. CONCLUSION: These 48-week interim data demonstrate that the LBAP system offers a safe and effective therapy to reduce weight in severely obese patients. PMID- 22078936 TI - Combined group and individual model for postbariatric surgery follow-up care. AB - BACKGROUND: The prevalence of bariatric surgery in the United States has increased significantly during the past decade, increasing the number of patients requiring postbariatric surgery follow-up care. Our objective was to develop and implement an efficient, financially viable, postbariatric surgery practice model that would be acceptable to patients. The setting was the Mayo Clinic (Rochester, MN). METHODS: By monitoring the attendance rates and using patient surveys, we tested patient acceptance of a new, shared medical appointment practice model in the care of postbariatric surgery patients. Efficiency was assessed by comparing differences in time per patient and total provider time required between the former and new care models. Individual-only patient/provider visits were replaced by combined group and individual visits (CGV). RESULTS: Our CGV model was well attended and accepted. The patient attendance rate was >90% at all postoperative follow-up points. Furthermore, 83%, 85.2%, and 75.7% of the 3-, 6-, and 12-month postbariatric surgery patients, respectively, responded that they would not prefer to have only individual visits with their healthcare providers. The CGV model also resulted in greater time efficiency and cost reduction. On average, 5 patients were seen within 4.9 provider hours compared with 10.4 provider hours with the individual-only patient/provider visit model. Furthermore, the average billable charge for the CGV model's group medical nutrition therapy was 50-64% less than the equivalent individual medical nutrition therapy used in the individual-only patient/provider visit model. CONCLUSION: Shared medical appointments have a valuable role in the care of the postbariatric surgery population, offering a time- and cost-effective model for healthcare provision that is well-accepted by patients. PMID- 22078937 TI - Decreased insulin secretion in islets from protein malnourished rats is associated with impaired glutamate dehydrogenase function: effect of leucine supplementation. AB - We herein studied the role of glutamate dehydrogenase (GDH), in response to leucine (LEU) supplementation, upon insulin secretion of malnourished rats. Weaned male Wistar rats were fed normal-protein (17%) or low-protein diet (6%, LP) for 8 weeks. Half of the rats of each group were supplemented with LEU (1.5%) in the drinking water for the following 4 weeks. Gene and protein expressions, static insulin secretion, and cytoplasmic Ca(2+) oscillations were measured. Glutamate dehydrogenase messenger RNA was 58% lower in LP islets, and LEU supplementation augmented it in 28%. The LP islets secreted less insulin when exposed to 20 mmol/L LEU, 20 mmol/L LEU + 2 mmol/L glutamine (with or without 5 mmol/L aminooxyacetic acid, a branched chain aminotransferase inhibitor, or 20 MUmol/L epigallocatechin gallate, a GDH inhibitor), 20 mmol/L alpha ketoisocaproate, glutamine + 20 mmol/L beta-2-aminobicyclo[2.2.1]heptane-2 carboxylic acid (a GDH activator), and 22.2 mmol/L glucose. Leucine supplementation augmented insulin secretion to levels found in normal-protein islets in all the above conditions, an effect that was blunted when islets were incubated with epigallocatechin gallate. The glutamine + beta-2 aminobicyclo[2.2.1]heptane-2-carboxylic acid-induced increased [Ca(2+)](i) and oscillations were higher than those for LP islets. Leucine supplementation normalized these parameters in LP islets. Impaired GDH function was associated with lower insulin release in LP islets, and LEU supplementation normalized insulin secretion via restoration of GDH function. In addition, GDH may contribute to insulin secretion through ameliorations of Ca(2+) handling in LP islets. PMID- 22078938 TI - In mammalian muscle, SIRT3 is present in mitochondria and not in the nucleus; and SIRT3 is upregulated by chronic muscle contraction in an adenosine monophosphate activated protein kinase-independent manner. AB - In selected cell lines, it appears (a) that metabolic stressors induce the translocation of SIRT3 from the nucleus to mitochondria and (b) that SIRT3 may contribute to the regulation of mitochondrial biogenesis and/or fatty acid utilization. We have examined in mammalian muscle (1) the association between SIRT3 protein content and muscle oxidative capacity and mitochondrial fatty acid oxidation, (2) the subcellular location of SIRT3, (3) whether exercise induces the translocation of SIRT3 from the nucleus to the mitochondria, and (4) the response of SIRT3 protein to stressors known to induce mitochondrial biogenesis (chronic muscle stimulation and 5-aminoimidazole-4-carboxamide-1-beta-d ribofuranoside administration). SIRT3 protein displayed hierarchical expression based on oxidative potential of muscle tissues (heart >> red >> white). In contrast to studies in some cell lines, metabolic stress (exercise) did not induce the translocation of SIRT3 from the nucleus to mitochondria, as SIRT3 was only present in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria, not in the nucleus. Chronic stimulation increased muscle mitochondrial content and SIRT3 protein in SS (+33%) and IMF (+27%) mitochondria (P < .05). In contrast, chronic 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside administration, while inducing mitochondrial biogenesis, did not alter SS or IMF mitochondrial SIRT3 protein content. These studies have shown that, in muscle, SIRT3 (a) scales with muscle oxidative capacity and with enzymes regulating fatty acid oxidation, (b) in resting muscle is localized to SS and IMF mitochondria and not nuclei, (c) in contracting muscle is not acutely translocated to mitochondria, and (d) is upregulated with chronic stimulation in an adenosine monophosphate-activated protein kinase-independent manner. PMID- 22078939 TI - Ultrasound-aided resorbable osteosynthesis of fractures of the mandibular condylar base: an experimental study in sheep. AB - We evaluated the osteosynthesis of condylar fractures using resorbable mini plates and ultrasound-aided insertion of pins clinically and histologically. Stability was greater than that with resorbable screws because of the fusion of pin and plate. Long term evaluation showed complete resorption of the polymeric osteosynthesis material. PMID- 22078940 TI - Transcriptional deregulation of homeobox gene ZHX2 in Hodgkin lymphoma. AB - Recently, we identified a novel chromosomal rearrangement in Hodgkin lymphoma (HL), t(4;8)(q27;q24), which targets homeobox gene ZHX2 at the recurrent breakpoint 8q24. This aberration deletes the far upstream region of ZHX2 and results in silenced transcription pinpointing loss of activatory elements. Here, we have looked for potential binding sites within this deleted region to analyze the transcriptional deregulation of this tumor suppressor gene in B-cell malignancies. SiRNA-mediated knockdown and reporter gene analyses identified two transcription factors, homeodomain protein MSX1 and bZIP protein XBP1, directly regulating ZHX2 expression. Furthermore, MSX1-cofactor histone H1C mediated repression of ZHX2 and showed enhanced expression levels in cell line L-1236. As demonstrated by fluorescence in situ hybridization and genomic array analysis, the gene loci of MSX1 at 4p16 and H1C at 6p22 were rearranged in several HL cell lines, correlating with their altered expression activity. The expression of XBP1 was reduced in 6/7 HL cell lines as compared to primary hematopoietic cells. Taken together, our results demonstrate multiple mechanisms decreasing expression of tumor suppressor gene ZHX2 in HL cell lines: loss of enhancing binding sites, reduced expression of activators MSX1 and XBP1, and overexpression of MSX1 corepressor H1C. Moreover, chromosomal deregulations of genes involved in this regulative network highlight their role in development and malignancy of B-cells. PMID- 22078942 TI - Modelling Marek's disease virus (MDV) infection: parameter estimates for mortality rate and infectiousness. AB - BACKGROUND: Marek's disease virus (MDV) is an economically important oncogenic herpesvirus of poultry. Since the 1960s, increasingly virulent strains have caused continued poultry industry production losses worldwide. To understand the mechanisms of this virulence evolution and to evaluate the epidemiological consequences of putative control strategies, it is imperative to understand how virulence is defined and how this correlates with host mortality and infectiousness during MDV infection. We present a mathematical approach to quantify key epidemiological parameters. Host lifespan, virus latent periods and host viral shedding rates were estimated for unvaccinated and vaccinated birds, infected with one of three MDV strains. The strains had previously been pathotyped to assign virulence scores according to pathogenicity of strains in hosts. RESULTS: Our analyses show that strains of higher virulence have a higher viral shedding rate, and more rapidly kill hosts. Vaccination enhances host life expectancy but does not significantly reduce the shedding rate of the virus. While the primary latent period of the virus does not vary with challenge strain nor vaccine treatment of host, the time until the maximum viral shedding rate is increased with vaccination. CONCLUSIONS: Our approach provides the tools necessary for a formal analysis of the evolution of virulence in MDV, and potentially simpler and cheaper approaches to comparing the virulence of MDV strains. PMID- 22078941 TI - A point prevalence survey of health care-associated infections in Canadian pediatric inpatients. AB - BACKGROUND: Health care-associated infections (HAIs) cause considerable morbidity and mortality to hospitalized patients. The objective of this point prevalence study was to assess the burden of HAIs in the Canadian pediatric population, updating results reported from a similar study conducted in 2002. METHODS: A point prevalence survey of pediatric inpatients was conducted in February 2009 in 30 pediatric or combined adult/pediatric hospitals. Data pertaining to one 24 hour period were collected, including information on HAIs, microorganisms isolated, antimicrobials prescribed, and use of additional (transmission based) precautions. The following prevalent infections were included: pneumonia, urinary tract infection, bloodstream infection, surgical site infection, viral respiratory infection, Clostridium difficile infection, viral gastroenteritis, and necrotizing enterocolitis. RESULTS: One hundred eighteen patients had 1 or more HAI, corresponding to a prevalence of 8.7% (n = 118 of 1353, 95% confidence interval: 7.2-10.2). Six patients had 2 infections. Bloodstream infections were the most frequent infection in neonates (3.0%), infants (3.1%), and children (3.5%). Among all patients surveyed, 16.3% were on additional precautions, and 40.1% were on antimicrobial agents, whereas 40.7% of patients with a HAI were on additional precautions, and 89.0% were on antimicrobial agents. CONCLUSION: Overall prevalence of HAI in 2009 has remained similar to the prevalence reported from 2002. The unchanged prevalence of these infections nonetheless warrants continued vigilance on their prevention and control. PMID- 22078943 TI - High prevalence of pathogenic Leptospira in wild and domesticated animals in an endemic area of China. AB - OBJECTIVE: To assess the prevalence of Leptospira detected in wildlife and domesticated animals in Jiangxi Province, China, in. METHODS: Urine samples from 28 buffaloes and kidney samples from 50 pigs, 50 dogs and 38 rats were collected from Fuliang and Shangrao County, Jiangxi Province, China, in October 2009. Polymerase chain reaction(PCR)and culture analyses were used to detect Leptospira. The cultured isolates were typed using the microscopic agglutination test(MAT). RESULTS: The results showed that rats potentially serve as the main reservoir of leptospiral infection, followed by dogs. Although 16% of rats (6/38) were positive using culture analysis, PCR analysis using the diagnostic primers G1/G2 and B64I/B64II or lipL32 showed identification as 50% and 24%, respectively, of the rat samples as positive for the presence of leptospiral DNA. CONCLUSIONS: PCR-based detection of leptospiral DNA in infected kidney tissues of reservoirs is more efficient when using G1/G2 primers than lipL32 primers. However, the latter primers have a potential application for detection in urine samples. The alarmingly high prevalence of leptospiral DNA in the wild rat population near human habitation underscores the utility of routine Leptospira surveillance, preferably using PCR methods, which are more sensitive than traditional culture-based methods. PMID- 22078944 TI - Molecular characterization of VP4, VP6, VP7 and NSP4 genes of group B rotavirus strains from outbreaks of gastroenteritis. AB - OBJECTIVE: To characterize VP4, VP6, VP7 and NSP4 genes of representative GBR strains (NIV-005625, NIV-04622 and NIV-094456) detected as the major etiologic agent in the outbreaks of gastroenteritis in western India. METHODS: Fecal specimens collected during the outbreaks of gastroenteritis were processed for RNA isolation, RT-PCR using GBR VP4, VP6, VP7 and NSP4 gene specific primers, nucleotide sequencing of the amplicons and phylogenetic analysis of the sequences. RESULTS: Phylogenetic analysis of all of the VP4, VP6, VP7 and NSP4 gene sequences revealed clustering of GBR strains in Indian-Bangladeshi lineage of genotype G2 with 95.8%-99.4% nucleotide and 97.3%-100.0% amino acid identities. However, all three strains showed the presence of unique amino acid substitutions in the VP4 protein suggesting alteration in the antigenicity of outbreak strains of GBR. The VP8* and VP5* regions of VP4 proteins showed respectively 0.5%-6.3% and 0.2%-1.1% amino acid divergence from human GBR strains of Indian-Bangladeshi lineage. CONCLUSIONS: These data confirm the reported variability of VP8* region and suggest the possible role of this region in the perpetuation of GBR infections in the environment. This is the first study to document the phylogenetic relationship of VP4, VP6, VP7 and NSP4 genes of GBR strains detected in the outbreaks of gastroenteritis from India with the GBR strains from other parts of world. PMID- 22078945 TI - Bioinformatics analysis on ORF1 protein of Torque teno virus (SANBAN isolate). AB - OBJECTIVE: To analyze the sequence of ORF1 protein of Torque teno virus to prepare for the future hybrid experiments. METHODS: The sequence of ORF1 protein of Torque teno virus was analyzed by bioinformatics using some web tools. RESULTS: The most likely cleavage site was between position 14aa and 15aa and signal peptide may be position 1aa-14aa. Two possible transmembrane helices from inside to outside and three possible transmembrane helices from outside to inside were found. The position 509 (NKTN) was the potential N-glycosylation site. The speculative molecular weight of TTV ORF1 protein, which may be a kind of unstable protein was 88 705.7 Da. 1aa-91aa and 278aa-361aa were localized in non-regular secondary structure region. CONCLUSIONS: TTV ORF1 protein may be a nuclear protein which contains two non-regular secondary structure region. 265aa to 486aa and 510aa to 679aa may be the two approciate fragments to construct the plasmids, which would be prepared for the future hybrid experiments to study the functional positions of the protein and the interactions between TTV and its hosts. Bioinformatics analysis would possibly make it easier to study the protein's function. PMID- 22078946 TI - Immunochemical characterization of antigens of Brucella canis and their use in seroprevalence study of canine brucellosis. AB - OBJECTIVE: To explore immunochemical characterization of antigens of Brucella canis (B. canis), and the use in seroprevalence study of canine brucellosis. METHODS: External hot phosphate buffer saline extract (HPBSE) and internal sonicated (SA) antigens were prepared from B. canis strain MEX 51 and immunochemically characterized. These antigens were used to test 527 serum samples of dogs by 2-mercaptoethanol-tube agglutination test (2 ME-TAT), agar gel immunodiffusion test (AGID), dot-ELISA and indirect enzyme-linked immunosorbent assay (I-ELISA) to assess the seroprevalence of canine brucellosis. RESULTS: The protein content of HPBSE and SA antigens was 0.387 mg/mL and 0.195 mg/mL, respectively, whereas carbohydrate content was 0.174 mg/mL and 0.150 mg/mL, respectively. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (12.5%) of HPBSE and SA, revealed 6 and 8 visible peptide bands ranging from 18 80 kDa and 12-45 kDa, respectively. Western blot analysis showed immunodominant bands of MW 12, 28, 39 and 45 kDa for HPBSE and 20-24 kDa for SA. The AGID revealed HPBSE as more specific antigen than SA but both I-ELISA and dot-ELISA indicated SA antigen to be more specific and reliable than HPBSE. The seroprevalence of canine brucellosis was 2.27% by 2ME-TAT, 1.5% by AGID, 3.03% by dot-ELISA and 16.12% by I-ELISA. CONCLUSIONS: On the basis of the results of present study, we concluded that HPBSE is suitable antigen for AGID, which is more specific; whereas SA antigen is suitable for I-ELISA, which is highly sensitive. Therefore, initial screening of serum samples should be carried out by I-ELISA followed by confirmation with AGID. PMID- 22078947 TI - In vitro antiplasmodial activity of methanolic extracts from seaweeds of South West Coast of India. AB - OBJECTIVE: To identify the in vitro antiplasmodial activity of seaweed plants against Plasmodium falciparumstrains. METHODS: A total of eight seaweeds were collected from Kanyakumari district, Tamilnadu, India. The in vitro antiplasmodial activity was performed in 96 well plates against Plasmodium falciparum, and preliminary phytochemcial analysis were performed for the extracts. RESULTS: Of the selected plants Enteromorpha intestinalis (2.61%) showed maximum percentage of extraction. The minimum concentration of inhibitory (IC50) value was observed with Chaetomorpha antennina [(26.37+/-4.14) MUg/mL] further, the positive controls such as chloroquine and artemether showed antiplasmodial activities (IC50) with (19.10+/-5.93) and (6.03+/-0.21) MUg/mL concentrations, respectively. The preliminary phytochemical analysis of the seaweed extracts showed a variety of phytochemical constituents such as carboxylic acids, phenols, protein, resins, steroids and sugars. CONCLUSIONS: The antiplasmodial activity of the seaweed extract might due to the presence of sugars and phenolic compounds. From the present findings, it is concluded that, the seaweed extract of Chaetomorpha antennina can be further used as a putative antiplasmodial drugs in near future. PMID- 22078948 TI - Synthesis and evaluation of novel analogues of mangiferin as potent antipyretic. AB - OBJECTIVE: To screen different analogues of mangiferin pharmacologically for antipyretic activity. METHODS: The naturally occurring xanthone glycoside mangiferin was isolated by column chromatography from the ethanolic extract of stem bark of Mangifera indica. Mangiferin was further converted to 5-(N phenylamino methyleno) mangiferin, 5-(N-p-chlorophenylamino methyleno) mangiferin, 5-(N-2-methyl phenylamino methyleno) mangiferin, 5-(N-p-methoxy phenylamino methyleno) mangiferin, 5-(N, N-diphenylamino methyleno) mangiferin, 5 (N-alpha-napthylamino methyleno) mangiferin and 5-(N-4-methyl phenylamino methyleno) mangiferin analogues. The synthesized compounds were further screened for antipyretic activity along with mangiferin at a dose level of 100 and 200 mg/kg. Mangiferin and its analogues were characterized by melting point andR(f)value determination and through spectral technique like UV, IR, and NMR spectral analysis. RESULTS: The antipyretic activity of mangiferin as well as all analogues was found to be more significant in at higher dose ie. 200 mg/kg which was depicted through a decrease in rectal temperature up to 3 h. CONCLUSIONS: The antipyretic activity of mangiferin and its analogues may be attributed to inhibition in synthesis of TNF-alpha and anti-oxidant activity associated with amelioration of inflammatory actions of cytokines. PMID- 22078949 TI - Protective effect of Amorphophallus campanulatus (Roxb.) Blume. tuber against thioacetamide induced oxidative stress in rats. AB - OBJECTIVE: To identify the phytochemical constituents of Amorphophallus campanulatus (A. campanulatus) tuber and to evaluate its antioxidant potential through in vitro and in vivo models. METHODS: Phytochemical screening and in vitro antioxidant activities of A. campanulatus tuber n-hexane extract (ACHE) and methanolic extract (ACME) were evaluated using DPPH, hydroxyl radical, reducing power and total antioxidant capacity assays. The total phenolic and flavonoid contents were also investigated. The protective potential of two different doses of ACME (125 and 250 mg/kg) was also evaluated against thioacetamide (TAA) induced oxidative stress in rats. Silymarin used as a standard drug control. Hepatotoxicity was assessed by quantifying the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant potential of ACME were also evaluated by the estimation of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (Thiobarbituric acid reactive substances) in hepatic and renal tissues. Histopathologic changes of liver were also evaluated. RESULTS: In vitro studies revealed that ACME has higher antioxidant and radical scavenging activity than ACHE, which may be attributed to its higher phenolic and flavonoid content. ACME significantly prevented the elevation of serum AST, ALT, ALP, LDH, and tissue malondialdehyde levels(P < 0.05). Hepatic and renal GSH, GST, GR, GPx, and catalase levels were remarkably increased by the treatment with the extract. Quantification of histopathological changes also supported the dose dependent protective effects of ACME. CONCLUSIONS: The results do suggest that A. campanulatus tuber could be considered as a potential source of natural antioxidant. PMID- 22078950 TI - Comparison of anti-atherosclerotic effects of two different extracts from leaves of Mallotus furetianus. AB - OBJECTIVE: To compare the anti-atherosclerotic effects of two different extracts from the leaves of Mallotus furetianus by using rat model of atherosclerosis. METHODS: The air-dried powdered Mallotus furetianus leaves were extracted with ethanol and then evaporated. The ethanol extract was experienced Diaion HP-20 CC with a gradient of MeOH and H2O (50:50, 100:0, v/v) and two fractions, Mallotus furetianus A (Mf A) and Mallotus furetianus B (Mf B) were obtained. Rats were divided into control, atherosclerosis and vitamin E, Mf A and Mf B treated groups. Atherosclerotic model was established by administering a loading dose of vitamin D3 and feeding standard diet enriched with 2% cholesterol, 0.5% porcine cholate, 0.2% methimazole, 5% sugar, 10% pork fat. Vitamin E (0.20 g/kg), Mf A (0.053 g/kg), Mf B (0.057 g/kg) (with the potential) were administered to interfere with the development of atherosclerosis. After 9 weeks, rats were sacrificed and the blood lipid as well as composition of bile was examined. In addition, the thoracic aorta was harvested to evaluate histological changes and the intima-media thickness ratio. RESULTS: Atherosclerosis model was successfully established, administration of vitamin E, Mf A and Mf B increased excretion of total bilirubin in bile, decreased triglyeride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) level, enhanced ratio of high density lipoprotein-cholesterol and LDL-C in blood, improved histological changes and diminished intima-media thickness ratio of thoracic aorta in atherosclerotic rats. As for the difference in anti-atherosclerotic effects betweenMf A and Mf B, Mf A may be more powerful in declining TG level and Mf B may be more effective in decreasing TC level. CONCLUSIONS: The two different extracts, Mf A and Mf B can prevent the development of atherosclerosis, In detail, Mf A is more effective in regulating TG level and Mf B is more powerful in modulating TC level in atherosclerotic rats. PMID- 22078951 TI - Pharmacological effects of aqueous-ethanolic extract of Hibiscus rosasinensis on volume and acidity of stimulated gastric secretion. AB - OBJECTIVE: To explore the effects of extract of Hibiscus rosasinensis (H. rosasinensis) on the volume, free and total acidity of gastric secretion induced by carbachol. METHODS: Animals were kept on fasting for 48 h, then the pylorus of each animal was ligated. They were randomly divided into 5 groups and treated by carbachol at 600 MUg/kg. Then animals in group II - V were treated by H. rosasinensis extract at 250 and 500 mg/kg body weight, cimetidine at 2.5 mg/kg and verapamil at 10 mg/kg body weight intraperitoneally, respectively. The volume, free and total acidity of gastric secretion were observed and compared. RESULTS: It was found that the extract significantly reduced the volume, free and total acidity of gastric secretion (P<0.01). These reductions were comparable to cimetidine and verapamil. And the reduction in the volume and free acidity were more significant in cimetidine and verapamil treated group indicating that cimetidine and verapamil were more effective. CONCLUSIONS: The extract of H. rosasinensis can reduced the volume, free and total acidity of gastric secretion, and can be used effectively in the treatment of peptic ulcer. PMID- 22078952 TI - Antioxidant and antipyretic studies on Pothos scandens L. AB - OBJECTIVE: To investigate Pothos scandens for the in vitro antioxidant and antipyretic activity. METHODS: Preliminary phytochemicals, total phenolics and flavonoid contents were analyzed in leaf, stem and root samples. In vitro antioxidant activity was evaluated by different assays such as 2, 2-diphenyl-1 picrylhydrazyl (DPPH) radical scavenging, 2, 2'-azinobis-3-ethylbenzothiazoline-6 sulphonic acid (ABTS*+) radical scavenging, ferric-reducing antioxidant power (FRAP) assay, phosphomolybdenum reduction assay, metal chelating activity, superoxide anion radical scavenging activity, hydrogen peroxide and nitric oxide scavenging assay. The antipyretic activity of root methanol extract was studied by pyrexia induced by brewer's yeast on Wistar albino rats at concentration of 200 and 400 mg/kg using paracetamol as standard drug. RESULTS: The total phenolics and tannin content were found to be higher in ethanol extract of stem, whereas total flavonoid content was higher in acetone extract of root. The methanol extract of root showed highest free radical scavenging activity in assays namely ABTS assay (8 221.5 MUM TE/g extract), FRAP assay [514.4 mM Fe (II)/g extract], hydrogen peroxide (60.3%) and nitric oxide scavenging assays (58.7%). The DPPH assay and superoxide radical assay results revealed that the ethanol extract of root has remarkable free radical scavenging capacity (IC50 0.284 mg/mL and 70.84%). The antipyretic studies on methanol extract of root showed significant reduction of temperature in pyrexia induced rats at 200 and 400 mg/kg doses. CONCLUSIONS: These findings justify that Pothos scandens can be a valuable natural antioxidant and antipyretic source which seemed to provide potential nutraceuticals for human health. PMID- 22078953 TI - Antidiabetic activity of methanolic bark extract of Albizia odoratissima Benth. in alloxan induced diabetic albino mice. AB - OBJECTIVE: To evaluate the antidiabetic potential of methanolic extract of Albizia odoratissima Benth. bark in alloxan induced diabetic mice. METHODS: Group I (normal control) mice received only basal diet without any treatment. In Group- II (Diabetic control) mice, diabetes was induced by alloxan (150 mg/kg i.p.) and received only Tween 80, 5% v/v in normal saline. Group- III and Group- IV mice received metformin (10mg/kg) and gliclazide (10 mg/kg) as standard drugs. Group- V and VI mice received methanolic bark extract of Albizia odoratissimaat doses of 250 and 500 mg/kg body weight p.o., respectively. RESULTS: The results of the study indicates that Albizia odoratissima bark extract significantly (P<0.01) reduced the blood sugar level. The bark extract also significantly reduced the levels of serum cholesterol, triglycerides, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, alkaline phosphatase and decreases level of total proteins in alloxan induced diabetic mice. CONCLUSIONS: Methanolic extract of Albizia odoratissima has protective effects on the protection of vital tissues (pancreas, kidney, liver, heart and spleen), thereby reducing the causation of diabetes in experimental animals. PMID- 22078954 TI - Antidiabetic activity of alcoholic leaves extract of Alangium lamarckii Thwaites on streptozotocin-nicotinamide induced type 2 diabetic rats. AB - OBJECTIVE: To investigate antidiabetic potential of alcoholic leaves extract of Alangium lamarckii (A. lamarckii) on streptozotocin-nicotinamide induced type 2 diabetic rats. METHODS: Oral glucose tolerance test was done by inducing hyperglycemic state via administration of glucose in water (2g/kg). Single dose of alcoholic leaves extract of A. lamarckii (250 and 500 mg/kg, p.o.) were administered to normoglycemic, hyperglycemic rats. Type 2 diabetes was induced by single intraperitoneal injection of nicotinamide (110 mg/kg) followed by streptozotocin (65mg/kg). The study also included estimations of blood plasma glucose, lipid profile, liver glycogen, body weight and antioxidant status in normal and diabetic rats. RESULTS: Admistration of alcoholic extract of A. lamarckii at two dosage 250 and 500 mg/kg, p.o. did not showed any significant change in blood glucose level of normoglycemic rats (P>0.05), whereas, oral glucose tolerance test depicted reduction in blood glucose level (P<0.05). The streptozotocin-nicotinamide induced diabetic rats, significantly decreased the blood plasma glucose level (P<0.001) comparable to glibenclamide (10 mg/kg), restored the lipid profile and showed improvement in liver glycogen, body weight and antioxidant status in diabetic rats. CONCLUSIONS: Present finding demonstrated the significant antidiabetic activity of alcoholic leaves extract of A. lamarckii. PMID- 22078955 TI - In vitro antioxidant and antimicrobial activity cycloart-23-ene-3beta,-25-diol (B2) isolated from Pongamia pinnata (L. Pierre). AB - OBJECTIVE: To evaluate the in-vitro antioxidant and antimicrobial activity of cycloart-23-ene-3beta, 25-diol (called as B2) isolated from stem bark of Pongamia pinnata. METHODS: In vitro antioxidant activity of B2 was determined by methods for determination of DPPH radical scavenging, reducing power, superoxide anion radical scavenging, hydroxyl radical scavenging, hydrogen peroxide scavenging, metal chelating and nitric oxide radical scavenging at the doses of 20, 40, 60, 80 and 100 MUg/mL, respectively. beta-tocopherol with same concentration was used as a standard antioxidant. In vitro antimicrobial activity of B2 was determined by cup plate method in different concentration range of 10-100 MUg/mL. RESULTS: The results indicated that dose dependent % reduction against DPPH radical, reducing power, superoxide anion radical scavenging, hydroxyl radical scavenging, metal chelating, hydrogen peroxide scavenging and nitric oxide radical scavenging by B2 and beta-tocopherol. CONCLUSIONS: It is concluded that cycloart 23-ene 3beta, 25 diol (B2) showed dose dependent antioxidant activity. B2 showed more DPPH radical scavenging, reducing power, superoxide scavenging, hydroxyl radical scavenging, metal chelating scavenging, hydrogen peroxide radical scavenging and nitric oxide radical scavenging activity than beta-tocopherol and in case of antimicrobial activity B2 exhibited broad-spectrum activity against bacteria and strong activity against yeast type of fungi. PMID- 22078956 TI - Inhibition of the emergence of multi drug resistant Staphylococcus aureus by Withania somnifera root extracts. AB - OBJECTIVE: To search systematically for an alternative therapy with compounds particularly from plant origin. METHODS: Efficacy test of different root extracts of Withania somnifera (W. somnifera) (L) Dunal against multi drug resistant (MDR) Staphylococcus aureus (S. aureus) variants was performed following the agar well diffusion method. Evaluation of susceptibility pattern of the isolates was carried out by employing disk diffusion method using standard antibiotic disks. RESULTS: In vitro study with W. somnifera root extracts was found to be effective against all the MDR S. aureus strains isolated from local and patient sources. Different root extracts of WS showed different degree of effectiveness against the isolates. CONCLUSIONS: The major active principles responsible for the antibacterial efficacy were mainly present in methanol (MeOH)extract and ethanol (EtOH) extracts as well as in butanol (BuOH) extract fraction. Amongst all the extracts the BuOH fraction was found to be most active against all the isolates but aqueous extract was the least active one. Finally it may be concluded that the antimicrobials from W. somnifera may raise an alternative therapy for MDR staphylococcal infections in near future. PMID- 22078957 TI - Healing promoting potentials of roots of Ficus benghalensis L. in albino rats. AB - OBJECTIVE: To screen the wound healing activity of aqueous and ethanolic extract of roots of Ficus benghalensis. METHODS: Both the extracts were evaluated for wound healing by three modelsie. incision, excision and dead space wound. In incision and dead space the extracts were applied daily topically till the 10 th post wounding days while in excision model it was till the complete epithelialization process. Standard group were administered Povidone iodine ointment topically daily. The breaking strength, percentage of wound contraction, period of epithelialization, dry granulation weight and hydroxyproline content were observed. RESULTS: The result of the present study showed that both extracts were able to increase the breaking strength (incision model), decrease period of epithelialization, increase percentage wound contraction (excision model), increase hydroxyproline content (Dead space wound model) significantly compared with control group (P<0.05). CONCLUSIONS: Based on result we conclude that aqueous extract is more effective than ethanolic extract. However, it is needed more research to be carried out especially on toxicity studies of ethanolic extract. PMID- 22078958 TI - New insights into the mechanisms of cytomotive actin and tubulin filaments. AB - Dynamic, self-organizing filaments are responsible for long-range order in the cytoplasm of almost all cells. Actin-like and tubulin-like filaments evolved independently in prokaryotes but have converged in terms of many important properties. They grow, shrink, and move directionally within cells, using energy and information provided by nucleotide hydrolysis. In the case of microtubules and FtsZ filaments, bending is an essential part of their mechanisms. Both families assemble polar linear protofilaments, with highly conserved interfaces between successive subunits; the bonding at these longitudinal interfaces is nucleotide dependent. Better understanding of the mechanisms by which nucleotide hydrolysis affects the bonding between subunits in filaments, and other structural changes related to the nucleotide hydrolysis cycles, has emerged from recent X-ray crystallographic and electron microscopic structures, showing eukaryotic or prokaryotic protofilaments in various states. Detailed comparisons of the structures of related proteins from eubacteria, archaea, and eukaryotes are helping to illuminate the course of evolution. PMID- 22078959 TI - New insights into the role of mitochondria-associated endoplasmic reticulum membrane. AB - The mitochondria-associated endoplasmic reticulum membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) membrane that regulates ER mitochondria communications. The MAM is characterized by direct apposition to a mitochondrion, a unique lipid profile, and the expression of a unique set of proteins involved in Ca(2+) signaling, phospholipid biosynthesis, protein folding, and membrane tethering. The association of the MAM with a mitochondrion is in part cytoskeleton independent and dynamically changed by an elevation of the cytosolic Ca(2+) level. The mechanisms underlying the genesis of MAM are unclear but might involve COPI-dependent vesicular transport and soluble NSF attachment protein receptor. The MAM is recognized as a center for intermembrane transport of phospholipids and for direct Ca(2+) transmission to mitochondria that activates the tricarboxylic acid cycle. However, MAM might be also involved in the interorganelle transport of cholesterol, ceramides, ATP, and proteins as well as in proteasomal protein degradation and lipid droplet formation. Recent studies have begun to unveil the importance of interorganelle communication in the innate immune response to virus infection and in the pathophysiology of neurodegenerative/neurodevelopmental disorders. Thus, drug discovery aimed at regulating ER-to-mitochondria communication may open a new avenue in treatments of human diseases. PMID- 22078960 TI - Strategies for silencing and escape: the ancient struggle between transposable elements and their hosts. AB - Over the past several years, there has been an explosion in our understanding of the mechanisms by which plant transposable elements (TEs) are epigenetically silenced and maintained in an inactive state over long periods of time. This highly efficient process results in vast numbers of inactive TEs; indeed, the majority of many plant genomes are composed of these quiescent elements. This observation has led to the rather static view that TEs represent an essentially inert portion of plant genomes. However, recent work has demonstrated that TE silencing is a highly dynamic process that often involves transcription of TEs at particular times and places during plant development. Plants appear to use transcripts from silenced TEs as an ongoing source of information concerning the mobile portion of the genome. In contrast to our understanding of silencing pathways, we know relatively little about the ways in which TEs evade silencing. However, vast differences in TE content between even closely related plant species suggest that they are often wildly successful at doing so. Here, we discuss TE activity in plants as the result of a constantly shifting balance between host strategies for TE silencing and TE strategies for escape and amplification. PMID- 22078961 TI - Current progress and potential practical application for human pluripotent stem cells. AB - Pluripotent stem cells are able to give rise to all cell types of the organism. There are two sources for human pluripotent stem cells: embryonic stem cells (ESCs) derived from surplus blastocysts created for in vitro fertilization and induced pluripotent stem cells (iPSCs) generated by reprogramming of somatic cells. ESCs have been an area of intense research during the past decade, and two clinical trials have been recently approved. iPSCs were created only recently, and most of the research has been focused on the iPSC generation protocols and investigation of mechanisms of direct reprogramming. The iPSC technology makes possible to derive pluripotent stem cells from any patient. However, there are a number of hurdles to be overcome before iPSCs will find a niche in practice. In this review, we discuss differences and similarities of the two pluripotent cell types and assess prospects for application of these cells in biomedicine. PMID- 22078962 TI - Protein quality control, retention, and degradation at the endoplasmic reticulum. AB - In order to maintain proper cellular functions, all living cells, from bacteria to mammalian cells, must carry out a rigorous quality control process in which nascent and newly synthesized proteins are examined. An important role of this process is to protect cells against pathological accumulation of unfolded and misfolded proteins. The endoplasmic reticulum (ER) has evolved as a staging ground for secretory protein synthesis with distinct sites for entry, quality control, and exit. In the ER, most proteins are N-glycosylated, a posttranslational modification that defines the quality control pathway that the protein will undergo. The folding state of glycoproteins is revealed by specific modifications of their N-glycans. Regardless of size and posttranslational modifications, the folding states of all proteins must be identified as unfolded, properly folded, or terminally misfolded and accordingly subjected to ER retention and continued folding attempts, export and maturation, or retrotranslocation to the cytosol for degradation. These processes involve specialized machineries that utilize molecular chaperones, protein- and N-glycan modifying enzymes, and lectins for protein folding and quality control and ubiquitination and degradation machineries for disposal. All these machineries are regulated by a signaling pathway, the unfolded protein response, which upregulates ER functions when under the stress of high protein load. Here, we describe the molecular mechanisms that are implicated and discuss recent data that underline the importance of compartmentalization in the segregation of the various functions of the ER for their correct function. PMID- 22078963 TI - Relation of left ventricular end diastolic pressure to right ventricular end diastolic volume after operative treatment of tetralogy of fallot. AB - Left ventricular (LV) diastolic dysfunction is associated with poor outcomes after tetralogy of Fallot (TOF) repair, although its cause is not known, and its relation to right ventricular (RV) performance has never been examined. The aim of this study was to test the hypothesis that RV dilation leads to LV diastolic dysfunction after TOF repair. Patients with repaired TOF who underwent cardiac catheterization and cardiac magnetic resonance imaging within 6 months from January 2003 and April 2011 were reviewed to assess the relation of LV end diastolic pressure (LVEDP) and indexed RV end-diastolic volume (RVEDVi). Thirty eight patients were included at a median age of 10.1 years (range 0.6 to 54.7). There was a significant linear association between RVEDVi and LVEDP (p = 0.05). RV end-diastolic pressure (p <0.001), right pulmonary artery systolic pressure (p = 0.009), left pulmonary artery systolic pressure (p = 0.02), and total cardiopulmonary support time (p = 0.04) during TOF repair were also significantly associated with LVEDP. Compared to patients with LVEDP <12 mm Hg, those with LVEDP >=12 mm Hg had significantly higher mean RVEDVi (135.2 +/- 47.8 vs 98.6 +/- 28 ml/m(2), p = 0.007) and mean RV end-diastolic pressure (11.7 +/- 1.6 vs 8.5 +/ 2.8 mm Hg, p = 0.0003). In conclusion, after TOF repair, LVEDP is significantly associated with RVEDVi. Furthermore, mean RVEDVi is significantly higher in patients with LVEDP >=12 mm Hg. These findings support the theory that RV dilation may impair LV diastolic function and that LV parameters may also be important to consider in determining timing of pulmonary valve replacement. PMID- 22078964 TI - Predictors of depressed left ventricular function in patients presenting with ST elevation myocardial infarction. AB - Early in the course of ST-segment elevation myocardial infarction (STEMI), therapies that may harm patients who develop left ventricular (LV) dysfunction, such as beta-blockers, are often administered. The investigators analyzed the ACTIVATE-SF database, a registry of consecutive STEMI activations presenting to 2 medical centers at the University of California, San Francisco. LV dysfunction was defined as an ejection fraction <=40% on echocardiography. Of 211 patients included in the analysis, 66 (31%) had LV ejection fractions <=40%. Patients with LV dysfunction were older (63 +/- 15 vs 56 +/- 13 years, p = 0.002). In multivariate regression models, decreased renal function (reference group, creatinine <1.0 mg/dl; adjusted odds ratio [AOR] creatinine >1.5 mg/dl 6.35, 95% confidence interval [CI] 1.66 to 24.31, p = 0.007), a history of coronary artery disease (AOR 3.12, 95% CI 1.26 to 7.71, p = 0.014), ST-segment elevation >2 mm on 12-lead electrocardiography (AOR 2.78, 95% CI 1.31 to 5.87, p = 0.008), and need for mechanical ventilation (AOR 3.98, 95% CI 1.41 to 11.19, p = 0.009) increased the odds of LV dysfunction. Inferior ST-segment elevations were associated with 88% decreased odds of LV dysfunction (AOR 0.12, 95% CI 0.06 to 0.35, p <0.001). A prediction score using these characteristics stratified patients into low-, intermediate-, and high-risk groups for LV dysfunction; positive likelihood ratios for LV dysfunction in these groups were 0.07, 1.14, and 4.93, respectively. In conclusion, 5 key predictors of in-hospital LV dysfunction after STEMI were identified; a risk score based on these predictors helps to quickly identify patients presenting with STEMI who are at the highest risk for developing significant LV dysfunction and could guide optimal therapeutic choices. PMID- 22078965 TI - Implications of ST-segment elevation in leads V5 and V6 in patients with reperfused inferior wall acute myocardial infarction. AB - During inferior acute myocardial infarction, ST-segment elevation (ST?) often occurs in leads V(5) to V(6), but its clinical implications remain unclear. We examined the admission electrocardiograms from 357 patients with a first inferior acute myocardial infarction who had Thrombolysis In Myocardial Infarction 3 flow of the right coronary artery or left circumflex artery within 6 hours after symptom onset. The patients were divided according to the presence (n = 76) or absence (n = 281) of ST? >2 mm in leads V(5) and V(6). Patients with ST? in leads V(5) and V(6) were subdivided into 2 groups according to the degree of ST? in leads III and V(6): ST? in lead III greater than in V(6) (n = 53) and ST? in lead III equal to or less than in V(6) (n = 23). The perfusion territory of the culprit artery was assessed using the angiographic distribution score, and a mega artery was defined as a score of >=0.7. ST? in leads V(5) and V(6) with ST? in lead III greater than in V(6) and ST? in leads V(5) and V(6) with ST? in lead III equal to or less than in V(6) were associated with mega-artery occlusion and impaired myocardial reperfusion, as defined by myocardial blush grade 0 to 1. Right coronary artery occlusion was most common (96%) in the former, and left circumflex artery occlusion was most common (96%) in the latter, especially proximal left circumflex occlusion (74%). Multivariate analysis showed that ST? in leads V(5) and V(6) with ST? in lead III greater than that in V(6) (odds ratio 4.81, p <0.001) and ST? in leads V(5) and V(6) with ST? in lead III equal or less than that in V(6) (odds ratio 5.96, p <0.001) were independent predictors of impaired myocardial reperfusion. In conclusion, ST? in leads V(5) and V(6) suggests a greater risk area and impaired myocardial reperfusion in patients with inferior acute myocardial infarction. Furthermore, comparing the degree of ST? in lead V(6) with that in lead III is useful for predicting the culprit artery. PMID- 22078966 TI - Relation between previous angiotensin-converting enzyme inhibitor use and in hospital outcomes in acute coronary syndromes. AB - Angiotensin-converting enzyme (ACE) inhibitor use in patients at high risk of coronary artery disease has been associated with a decrease in the risk of myocardial infarction (MI) and death. However, it is unclear whether chronic use of these agents modifies the course and outcome of an acute coronary syndrome (ACS). This study assessed the association between chronic use of ACE inhibitors and clinical outcomes in patients with ACS. From 1999 through 2008, 13,632 Canadian patients with ACS were identified in the Global Registry of Acute Coronary Events (GRACE), the expanded GRACE (GRACE(2)), and the Canadian Registry of Acute Coronary Events (CANRACE). Patients were stratified by previous use of an ACE inhibitor. Clinical characteristics, in-hospital treatment, and outcomes were compared between the 2 groups. Multivariable logistic regression analysis adjusting for GRACE risk score and other clinical factors was performed. Patients receiving an ACE inhibitor before the ACS had a higher prevalence of diabetes (40.6% vs 21.2%, p <0.001), previous MI (51.8% vs 23.3%, p <0.001), heart failure (18.0% vs 6.9%), and higher GRACE scores at presentation (133 vs 124, p <0.001). Multivariable analysis demonstrated no significant association between previous ACE inhibitor use and death (adjusted odds ratio [OR] 1.15, confidence interval [CI] 0.90 to 1.49, p = 0.27), in-hospital re-MI (adjusted OR 0.99, CI 0.78 to 1.25, p = 0.91), or the composite end point of death/re-MI (adjusted OR 1.01, CI 0.84 to 1.20, p = 0.94). In conclusion, previous use of an ACE inhibitor is not independently associated with improved in-hospital outcomes after an ACS. PMID- 22078967 TI - The effect of vessel depth, diameter, and location on ultrasound-guided peripheral intravenous catheter longevity. AB - INTRODUCTION: Ultrasound-guided peripheral intravenous catheters (USGPIVs) have been observed to have poor durability. The current study sets out to determine whether vessel characteristics (depth, diameter, and location) predict USGPIV longevity. METHODS: A secondary analysis was performed on a prospectively gathered database of patients who underwent USGPIV placement in an urban, tertiary care emergency department. All patients in the database had a 20-gauge, 48-mm-long catheter placed under ultrasound guidance. The time and reason for USGPIV removal were extracted by retrospective chart review. A Kaplan-Meier survival analysis was performed. RESULTS: After 48 hours from USGPIV placement, 32% (48/151) had failed prematurely, 24% (36/151) had been removed for routine reasons, and 44% (67/151) remained in working condition yielding a survival probability of 0.63 (95% confidence interval [CI], 0.53-0.70). Survival probability was perfect (1.00) when placed in shallow vessels (<0.4 cm), moderate (0.62; 95% CI, 0.51-0.71) for intermediate vessels (0.40-1.19 cm), and poor (0.29; 95% CI, 0.11-0.51) for deep vessels (>=1.2 cm); P < .0001. Intravenous survival probability was higher when placed in the antecubital fossa or forearm locations (0.83; 95% CI, 0.69-0.91) and lower in the brachial region (0.50; 95% CI, 0.38-0.61); P = .0002. The impact of vessel depth and location was significant after 3 hours and 18 hours, respectively. Vessel diameter did not affect USGPIV longevity. CONCLUSION: Cannulation of deep and proximal vessels is associated with poor USGPIV survival. Careful selection of target vessels may help improve success of USGPIV placement and durability. PMID- 22078968 TI - Removal of trace organic contaminants by a membrane bioreactor-granular activated carbon (MBR-GAC) system. AB - The removal of trace organics by a membrane bioreactor-granular activated carbon (MBR-GAC) integrated system were investigated. The results confirmed that MBR treatment can be effective for the removal of hydrophobic (log D>3.2) and readily biodegradable trace organics. The data also highlighted the limitation of MBR in removing hydrophilic and persistent compounds (e.g. carbamazepine, diclofenac, and fenoprop) and that GAC could complement MBR very well as a post-treatment process. The MBR-GAC system showed high removal of all selected trace organics including those that are hydrophilic and persistent to biological degradation at up to 406 bed volumes (BV). However, over an extended period, breakthrough of diclofenac was observed after 7320 BV. This suggests that strict monitoring should be applied over the lifetime of the GAC column to detect the breakthrough of hydrophilic and persistent compounds which have low removal by MBR treatment. PMID- 22078969 TI - Cloning and expression of a gene with phospholipase B activity from Pseudomonas fluorescens in Escherichia coli. AB - A gene from Pseudomonasfluorescens BIT-18 encoding a protein with phospholipase B activity (Pf-PLB) was cloned in E. coli BL21 (DE3). The open reading frame consists of 1272 bp and potentially encodes a protein of 423 amino acid residues with a calculated molecular mass of 45.8 kDa. The nucleotide sequence of Pf-PLB is 45%, 42%, 41%, 40%, 33%, and 31% identical to that of Bifidobacterium animals, Mycobacterium parascrofulaceum, Acidobacterium capsulatum, Lactobacillus johnsonii, Moraxella bovis, and Moraxella catarrhalis, respectively. The His tagged protein was purified by affinity chromatography and the eluted protein hydrolyzed both the 1- and 2-ester bond of phosphatidylcholine. The recombinant Pf-PLB had optimal activity at pH 6.0 and 30 degrees C, and it showed 20.1% higher efficiency in the conversion rate of the phosphorus content than the wild type. PMID- 22078971 TI - Radiotherapy and cervix cancer - university hospitals Birmingham experience with patients not suitable for concurrent chemoradiotherapy with cisplatin. PMID- 22078970 TI - Removal of oxytetracycline (OTC) in a synthetic pharmaceutical wastewater by a sequential anaerobic multichamber bed reactor (AMCBR)/completely stirred tank reactor (CSTR) system: biodegradation and inhibition kinetics. AB - An anaerobic multichamber bed reactor (AMCBR) was effective in removing both molasses-chemical oxygen demand (COD), and the antibiotic oxytetracycline (OTC). The maximum COD and OTC removals were 99% in sequential AMCBR/completely stirred tank reactor (CSTR) at an OTC concentration of 300 mg L(-1). 51%, 29% and 9% of the total volatile fatty acid (TVFA) was composed of acetic, propionic acid and butyric acids, respectively. The OTC loading rates at between 22.22 and 133.33 g OTC m(-3) d(-1) improved the hydrolysis of molasses-COD (k), the maximum specific utilization of molasses-COD (k(mh)) and the maximum specific utilization rate of TVFA (k(TVFA)). The direct effect of high OTC loadings (155.56 and -177.78 g OTC m(-3) d(-1)) on acidogens and methanogens were evaluated with Haldane inhibition kinetic. A significant decrease of the Haldane inhibition constant was indicative of increases in toxicity at increasing loading rates. PMID- 22078972 TI - Early chronotropic response analysis in head up tilt table test. PMID- 22078973 TI - Superior approach for radiofrequency ablation of common atrial flutter in patient with heterotaxy syndrome. PMID- 22078974 TI - An unexpected cause of acute ST-elevation: an unconsciously swallowed sewing needle migrating to the heart. PMID- 22078975 TI - Long-term course of stemi complicated by a moderate to severe pericardial effusion. Frequency of left ventricular pseudoaneurysm. PMID- 22078976 TI - Double right coronary artery or split right coronary artery? AB - The prevalence of congenital anomalies of the coronary arteries (CAAs) is reported to be approximately 0.2-1.4% of the general population. Of them, The double right coronary artery (RCA) is one of the rarest coronary anomalies. Nonetheless, there is no consensus of the definition of a double RCA until now. Several concepts have been proposed in order to define what is and is not a double RCA. So far, it was been reported 37 times and in 44 cases after a comprehensive literature search through the PubMed database, using the keywords "double right coronary artery," "duplicated right coronary artery," "dual right coronary artery" and "split right coronary artery." Most of the published articles (28 of 37 articles) used the name "double right coronary artery." Nevertheless, some investigators contended that a split RCA is anatomically the same anomaly as the improperly named "double right coronary artery". The debate between those who favor "double RCA" and those who favor "split RCA" indicate the need for a consensus regarding the nomenclature as well diagnostic criteria of such coronary anomalies. It is the time we need to reach a consensus of the nomenclature of this congenital coronary anomaly. PMID- 22078977 TI - Vectorcardiography shows cardiac memory and repolarization heterogeneity after ablation of accessory pathways not apparent on ECG. AB - BACKGROUND: Pacing induced cardiac memory is an established phenomenon, but following successful WPW ablation, cardiac memory was present on ECG in variable proportions of patients depending on accessory pathway (AP) location. We hypothesized that vectorcardiography (VCG), which is more sensitive than ECG, would show cardiac memory after WPW ablation independent of AP location. METHODS: Thirty-six patients were followed after successful AP ablation, 11 with overt posteroseptal (PS), 13 with overt left-sided (LS) and 12 with concealed APs (controls). VCGs were recorded the day before and after the procedure, >= once/week for 6-8 weeks and after >= 3 months. T vector and T-vector loop parameters were analyzed and compared. RESULTS: After ablation of overt APs, there was a correlation between the directions of the preexcited maximum QRS vector and the post-ablation maximum T-vector, confirming the presence of cardiac memory. Ablation of overt APs was followed by cardiac memory apparent in different directions. Thus, ablation of PS APs was followed by most pronounced changes in T-vector elevation and LS APs with significant changes only in T vector azimuth. Cardiac memory disappeared within a month in > 80% of cases. Furthermore, T-vector loop morphology changes suggested a period of repolarization heterogeneity immediately after ablation of overt APs. CONCLUSIONS: According to VCG analysis cardiac memory was present after ablation of overt APs independent of location as consistently as after ventricular pacing, and disappeared within a similar time frame during normal ventricular activation. In addition, signs of transient repolarization heterogeneity were observed after ablation of overt APs. PMID- 22078978 TI - Unruptured aneurysms of all sinus of Valsalva causing non-ST-elevation myocardial infarction. PMID- 22078979 TI - Effects of nebivolol or irbesartan in combination with hydrochlorothiazide on vascular functions in newly-diagnosed hypertensive patients: the NINFE (Nebivololo, Irbesartan Nella Funzione Endoteliale) study. AB - BACKGROUND: Arterial hypertension affects endothelial function and arterial stiffness. The angiotensin (AT1) receptor antagonist irbesartan improves endothelial function and arterial stiffness in hypertensive patients. Nebivolol, a beta(1)-selective beta blocker, reduces systemic vascular resistance and stimulates nitric oxide release thus exerting positive effects on vascular function. However, comparative studies on the vascular effects of third generation beta-blockers and AT1 receptor blockers are lacking. Aim of this randomized, double-blind study was to test the hypothesis of non-inferiority of nebivolol to irbesartan, both in association with hydrochlorothiazide, on endothelial function, arterial stiffness and central hemodynamic parameters in patients with arterial hypertension naive on therapy. METHODS: Sixty-five patients were randomized to receive irbesartan/hydrochlorothiazide (150 mg/12.5 mg day) or nebivolol/hydrochlorothiazide (5mg/12.5 mg day) for 8-weeks. Endothelial function, pulse wave velocity, augmentation index, central and brachial blood pressures were measured at baseline and at the end of the study. RESULTS: Systolic and diastolic central blood pressure, as well as brachial arterial pressure, decreased to a similar extent after both treatments. Similar changes in endothelial function between groups were detected at the end of the study. A significant reduction in pulse wave velocity, central blood pressure, and augmentation index adjusted for heart rate, was found in both the treatment groups at the end of the study, without significant differences between groups. CONCLUSIONS: The results of this study confirm the hypothesis of non-inferiority of short-term treatment with nebivolol compared to irbesartan, both in association with hydrochlorothiazide, on endothelial function, arterial stiffness and central hemodynamic parameters in hypertensive patients naive on therapy. PMID- 22078980 TI - Dissociation between anatomical and functional results after MitraClip implantation. PMID- 22078981 TI - Short-term effects of eicosapentaenoic acid on P wave signal-averaged electrocardiogram in patients with coronary artery disease. PMID- 22078982 TI - A case of myocardial infarction in a young female with subclinical hyperthyroidism. PMID- 22078983 TI - Circumferential myocardial contraction patterns in patients with idiopathic frequent premature ventricular complexes from the right ventricular outflow tract. AB - BACKGROUND: The pathogenesis of frequent premature ventricular complexes (PVCs) in patients without overt cardiovascular disease is considered idiopathic. Idiopathic PVCs are predominantly from the right ventricular outflow tract (RVOT) and considered a reversible cause of left ventricular (LV) dysfunction. OBJECTIVES: We investigated whether alternations in LV contraction patterns exist in patients with idiopathic frequent PVCs originating from the RVOT. METHODS: Segmental myocardial circumferential strain (CS)-time curves were acquired from 29 patients with idiopathic frequent RVOT-PVCs and 30 healthy subjects. Peak CS and the time to peak CS (TPcs) of each segment were analyzed, with the standard deviation of TPcs for 18 LV segments (SDtpcs) calculated. All values of patients with RVOT-PVCs were recorded during both sinus beats (PVC-S) and ventricular extrasystoles (PVC-V), respectively. RESULTS: The distribution of peak CS and TPcs in the PVC-V was opposite that of the healthy subjects. The distribution of TPcs of PVC-S within the different layers differed from that of healthy subjects. These patients had significantly greater dyssynchrony compared with the healthy subjects assessed by SDtpcs (healthy subjects: 6.7%+/-1.9%, PVC-S: 8.1%+/-3.1%, PVC-V: 9.7%+/-3.4%, healthy subjects vs. PVC-S p=0.04; healthy subjects vs. PVC-V p=0.001). Furthermore, a positive correlation was observed between PVC frequency and SDtpcs of PVC-S (r=0.44, p=0.02). CONCLUSIONS: Idiopathic frequent RVOT-PVCs can induce alterations in the LV myocardial contractile pattern during both sinus beats and ventricular extrasystoles. Circumferential contraction dyssynchrony of patients during sinus beats relates to PVC frequency. Therefore, attention should be paid to patients with frequent RVOT-PVCs, especially those with a high prevalence of PVCs. PMID- 22078984 TI - Autonomic activation during sleep and new-onset ambulatory hypertension in the elderly. AB - BACKGROUND: Sympathetic "overactivity" during night is a well recognized factor of hypertension development in adults. However, the deleterious effect of nocturnal autonomic activation in elderly remains controversial. METHODS: Subjects, all aged 65 years at baseline, were selected from the PROOF cohort study, a prospective observational cohort of subjects. Exclusion criteria were previous myocardial infarction, stroke, heart failure, type-1 diabetes, atrial fibrillation or anti-arrhythmic drug. Normotensive subjects were selected according to: 24-h ambulatory blood pressure (BP) measurements <135/85 mm Hg, absence of self-report antihypertensive treatment. Autonomic activation during sleep was evaluated from night-time ECG Holter recording. According the %VLFI (Very-Low Frequency component of Interbeat Interval Increment evaluated from heart rate variability analysis). Subjects with new-onset ambulatory hypertension were identified after two years when daytime ambulatory blood pressure was higher than 135/85 mm Hg or when they used an antihypertensive treatment. RESULTS: Among 428 normotensive subjects at inclusion, 62 (14.5%) were considered as hypertensives after two years. Univariate logistic regression model showed a significant association between abnormal %VLFI (>4%) and new-onset hypertension: OR = 1.78 (1.03-3.07). Male gender, increased body mass index and ambulatory systolic BP were also associated with increased risk of hypertension. After adjustment in the stepwise logistic regression, abnormal %VLFI was associated with an 82% increase in odds of new-onset hypertension, independently of systolic ABPM and body mass index. CONCLUSION: Repeated autonomic activation during sleep, whatever the origin of the phenomenon, may trigger hypertension development in the elderly. PMID- 22078985 TI - Dose-response relationship of baroreflex sensitivity and heart rate variability to individually-tailored exercise training in patients with heart failure. AB - BACKGROUND: Heart Rate Variability (HRV) and Baroreflex Sensitivity (BRS) are impaired in patients with Chronic Heart Failure (CHF) and carry negative prognosis. Exercise training improves these parameters. However, the relationship between exercise training with HRV and BRS has been investigated without regard for individual training loads. We tested the hypothesis that in CHF patients changes in HRV and BRS are dose-response related to individual volume/intensity training load (TL). METHODS: Twenty patients with stable postinfarction CHF under optimal medical treatment were randomized to either aerobic continuous training (ACT) or aerobic interval training (AIT) for 12weeks. Individualized TL was monitored by the Training Impulses (TRIMPi) method, which was determined using the individual HR and lactate profiling determined during a treadmill test at baseline. HRV (standard deviation of mean R-R interval) and BRS were assessed at rest and 3weeks apart, throughout the study. RESULTS: HRV, BRS and R-R interval increased significantly with training, being very highly correlated to the dose of exercise with a second-order regression model (r(2) ranged from 0.75 to 0.96; P<0.001), resembling a bell-shaped in the ACT, and an asymptotic-shaped curve in the AIT groups, respectively. These changes were accompanied by a significant increase in functional capacity. No significant differences were detected between ACT and AIT in any variable. CONCLUSIONS: These results suggest that improvements in HRV and BRS by exercise training in CHF patients are dose related to TL in a non-linear fashion on an individual basis, with optimal results at moderate doses of exercise. PMID- 22078986 TI - CoreValve deployment during cardiopulmonary resuscitation without angiographic injections guidance: an additional capability of Accutrak system? PMID- 22078987 TI - Response to "Sirolimus or paclitaxel drug eluting stent in left main disease: the winner is...". PMID- 22078988 TI - Systemic administration of bevacizumab increases the risk of cardiovascular events in patients with metastatic cancer. PMID- 22078989 TI - Acute Q fever myocarditis: thinking about a life-threatening but potentially curable condition. PMID- 22078990 TI - Navigating the mini-maze: systematic review of the first results and progress of minimally-invasive surgery in the treatment of atrial fibrillation. AB - BACKGROUND: In this paper we present a systematic literature overview and analysis of the first results and progress made with minimally-invasive surgery using RF energy in the treatment of AF. The minimally-invasive treatment for atrial fibrillation (AF) tries to combine the success rate of surgical treatment with a less invasive approach to surgery. It has the additional potential advantage of ganglion plexus (GP) ablation and left atrial appendage exclusion. Furthermore, additional left atrial ablation lines (ALAL) can be created in non paroxysmal AF patients. METHODS: For the search query multiple databases were used. Exclusion and inclusion criteria were applied to select the publications to be screened. All remaining articles were critically appraised and only relevant and valid articles were included in our results. RESULTS: Twenty-three studies were included. In 15 studies GPs around the pulmonary veins were ablated. In four studies ALAL were performed. Single procedure success rate was 69% (95% CI, range 58%-78%) without antiarrhythmic drugs (AAD) and 79% (95% CI, range 71%-85%) with AAD at one year follow-up. Mortality was 0.4%, and various complications were reported (3.2% surgical, 3.2% post-surgical, 2.6% cardiac, 2.1% pulmonary, 1.7% other). CONCLUSIONS: Twenty-three studies of minimally-invasive surgery for AF have been reviewed with success rates between that of the standard maze procedure and catheter ablation. These first combined results show promise; however, minimally-invasive surgery is still evolving, for instance by the recent inclusion of electrophysiological endpoints. Furthermore, the type of ALAL and the additional value of GP ablation have to be elucidated. PMID- 22078991 TI - Quantification of serum ferritin in the acute coronary syndrome: a puzzle still to be resolved? PMID- 22078992 TI - Heart failure and comorbid diabetes mellitus or chronic obstructive pulmonary disease: effects on mood in outpatients. PMID- 22078993 TI - Subsequent silent plaque rupture of nonculprit lesion in a patient with acute myocardial infarction. PMID- 22078994 TI - Advances in the chemistry of small molecule fluorescent probes. AB - Small molecule fluorophores are essential tools for chemical biology. A benefit of synthetic dyes is the ability to employ chemical approaches to control the properties and direct the position of the fluorophore. Applying modern synthetic organic chemistry strategies enables efficient tailoring of the chemical structure to obtain probes for specific biological experiments. Chemistry can also be used to activate fluorophores; new fluorogenic enzyme substrates and photoactivatable compounds with improved properties have been prepared that facilitate advanced imaging experiments with low background fluorescence. Finally, chemical reactions in live cells can be used to direct the spatial distribution of the fluorophore, allowing labeling of defined cellular regions with synthetic dyes. PMID- 22078995 TI - Differential gene expression in tea (Camellia sinensis L.) calli with different morphologies and catechin contents. AB - Tea (Camellia sinensis) is a commercially important crop that contains valuable secondary metabolites. To understand the molecular regulation of secondary metabolism in tea, we selected and analyzed two cell lines of tea callus (Yunjing63Y and Yunjing63X) that showed different morphological characteristics and catechin contents. Yunjing63Y callus was yellow and tight, while yunjing63X callus was white and loose. HPLC analyses showed that Yunjing63Y contained 3.71 times higher levels of catechins than Yunjing63X. Using cDNA amplified fragment length polymorphism (cDNA-AFLP) we identified 68 genes that were differentially expressed between the two lines. Of the 68 differentially expressed ESTs, 40 showed higher expressions in Yunjing63Y and 28 showed higher expressions in Yunjing63X. BLASTX comparisons classified these ESTs into seven functional groups; phenylpropanoid metabolism (2.9%), UDPG-dependent glucosyl transferase (8.8%), transcription factors (11.8%), transporters (13.2%), signal transduction (19.1%), other metabolism (26.5%), and unknown (17.7%). We used qRT-PCR to validate the expression of genes and ESTs, and found that genes associated with flavan-3-ols biosynthesis and metabolism were expressed at higher levels in Yunjing63Y than in Yunjing63X. In addition, the expression of ESTs associated with flavonoid biosynthesis, regulation and transport were higher in Yunjing63Y than in Yunjing63X. The full-length cDNA of a EST coding for a putative MYB transcription factor was amplified using rapid amplification of cDNA ends (RACE). The resulting 1270 bp long cDNA, named CsMYB1, contained a 933-bp ORF encoding a 310-amino acid protein with a predicted molecular weight of 105.27 kDa and a predicted isoelectric point of 4.85 and showed highest homology to plant MYBs likely involved in stress signaling. PMID- 22078996 TI - Immunolocalization of H(+)-ATPase and IRT1 enzymes in N(2)-fixing common bean nodules subjected to iron deficiency. AB - The demand for iron in leguminous plants increases during symbiosis, as the metal is utilised for the synthesis of various Fe-containing proteins in both plant and bacteroids. However, the acquisition of this micronutrient is problematic due to its low bioavailability at physiological pH under aerobic conditions. Induction of root Fe(III)-reductase activity is necessary for Fe uptake and can be coupled to the rhizosphere acidification capacity linked to the H(+)-ATPase activity. Fe uptake is related to the expression of a Fe(2+) transporter (IRT1). In order to verify the possible role of nodules in the acquisition of Fe directly from the soil solution, the localization of H(+)-ATPase and IRT1 was carried out in common bean nodules by immuno-histochemical analysis. The results showed that these proteins were particularly abundant in the central nitrogen-fixing zone of nodules, around the periphery of infected and uninfected cells as well as in the vascular bundle of control nodules. Under Fe deficiency an over-accumulation of H(+)-ATPase and IRT1 proteins was observed especially around the cortex cells of nodules. The results obtained in this study suggest that the increase in these proteins is differentially localized in nodules of Fe-deficient plants when compared to the Fe-sufficient condition and cast new light on the possible involvement of nodules in the direct acquisition of Fe from the nutrient solution. PMID- 22078997 TI - Bone mineral density, fracture, and vitamin D in adolescents and young women using depot medroxyprogesterone acetate. AB - STUDY OBJECTIVE: To evaluate bone mineral density (BMD) in adolescents and young adults treated with depot medroxyprogesterone acetate (DMPA). DESIGN, SETTING, PARTICIPANTS: Eighty-three healthy subjects, 13-20 years old, who received at least 3 DMPA injections in an urban adolescent clinic and underwent dual energy x ray absorptiometry (DXA) were evaluated by chart review. MAIN OUTCOME MEASURES: Anthropometric data, DMPA use, BMD of the spine and hip, fracture history, and vitamin D status were collected. RESULTS: Subjects were a median age of 16.4 years old (range 13-20 years) when DMPA was initiated. The median number of DMPA injections was 5 (range 3-18) before the first DXA. At the spine and hip, respectively, BMD was normal (Z-score > -1.0 SD) for most subjects (79%, 86%). Subjects who received > 5 injections were more likely to have low spinal BMD (Z score <= -2.0 SD) at first DXA (P = .018). In 15 subjects with repeat DXA measurements, after an additional median 6 injections, spinal BMD Z-score decreased by -0.33 +/- 0.10 (mean +/- SD, P = .004), as did absolute BMD at the hip (-0.019 +/- 0.007 g/cm(2), P = .014). History of fracture was not associated with initial or subsequent BMD measurements. Most (12/13, 92.3%) subjects with vitamin D measurements were deficient (25-hydroxy vitamin D < 20 ng/mL). CONCLUSIONS: Most subjects on DMPA had normal BMD at first DXA. Low spinal BMD was associated with longer DMPA use, and some BMD measurements declined with prolonged use. Fracture history is not an absolute contraindication to DMPA use in this population. Studies are needed to determine possible benefits of vitamin D supplementation in DMPA users. PMID- 22078998 TI - Paraspinal muscle function assessed with the flexion-relaxation ratio at baseline in a population of patients with back-related leg pain. AB - OBJECTIVE: The purpose of this study was to assess back muscle status at baseline in patients with back-related leg pain (BRLP) and to correlate those findings with baseline demographic and clinical factors. METHODS: Surface electromyography (EMG) and electromagnetic motion-tracking detected flexion-relaxation response in 135 patients with BRLP. Surface EMG electrodes were attached with standard skin preparation over the right and left paraspinal muscles at L3. Participants moved from upright standing into full forward flexion, rested flexed for 1 second, and returned to the upright position. A flexion-relaxation ratio (FRR) factor was calculated as the root mean square EMG amplitude during forward flexion divided by the activity at full flexion. RESULTS: High repeatability was found (intraclass correlation coefficient [ICC]([1,3]) = 0.94 and 0.86) between 3 cycles of assessment at the same session. Patients with BRLP exhibited low FRR values, indicating a loss of the flexion-relaxation response similar to that seen in low back pain patients. Patients with very low FRR had higher Roland-Morris Disability Questionnaire scores than the other patients, had increased incidence of straight leg raise test, and had decreased range and rate of forward flexion. CONCLUSIONS: A subgroup of patients with BRLP was identified with very low FRR who exhibited more disability and clinical findings and decreased motion. The use of the inverted FRR factor, expressing muscle activity at the fully flexed and resting position as a percentage of peak activity during flexion, provides more stable numerical behavior and another perspective on interpreting FRRs. PMID- 22078999 TI - Postural assessment of lumbar lordosis and pelvic alignment angles in adolescent users and nonusers of high-heeled shoes. AB - OBJECTIVE: The aims of this study were (1) to analyze the influence of wearing high-heeled shoes on lumbar lordosis and pelvic inclinations among adolescents aged between 13 and 20 years were users and nonusers of high-heeled shoes and (2) to correlate these postural angles with age. METHODS: Fifty adolescents from the nonuser group (NUG) of high-heeled shoes and 50 from the user group (UG) were evaluated. Postural assessments were obtained by photogrammetry under 2 conditions-barefoot and with high-heeled shoes-and analyzed using the evaluation postural software. The measured angles included lumbar lordosis and the horizontal alignment of the pelvis. Descriptive analyses were carried out, with a significance level of 5%. RESULTS: With high-heeled use, the NUG demonstrated rectification of the lumbar spine and pelvic retroversion, whereas the UG demonstrated hyperlordosis and pelvic anteversion. When barefoot, smaller lumbar lordosis angles for both groups were observed. However, the pelvic angles were lower for the UG group and higher for the NUG. The studied angles showed high reliabilities. Age was correlated with lumbar lordosis angles for the NUG in the barefoot condition and with pelvic alignments in both conditions for the UG. CONCLUSION: For the subjects in this study, the use of high-heeled shoes is correlated with increased lumbar lordosis and pelvic anteversions. Lumbar lordosis angles are correlated with age for the NUG when barefoot. PMID- 22079000 TI - Human subject research: reporting ethics approval and informed consent in 3 chiropractic journals. AB - OBJECTIVE: To date, there have been no reports of ethics board approval or informed consent within the chiropractic literature or within chiropractic research. The purpose of this study was to assess the reporting of ethics approval and informed consent in articles published during the 2008 volume year of 3 chiropractic research journals included in PubMed. METHODS: A quantitative assessment of the articles published in each journal for the 2008 volume year was performed. Information collected included if the article involved human subject research, if it reported ethics board approval, and if informed consent was given to subjects. Data were collected as descriptive statistics (frequency counts and percentages). RESULTS: In aggregate, 50 articles of a total of 143 published involved human subject research (35%). 44 reported ethics board approval (88%), and 28 reported that informed consent had been obtained (56%). Forty-five percent of articles published in the Journal of Manipulative and Physiological Therapeutics involved human subject research (39/87), of which 95% reported ethics board approval (37/39) and 64% reported informed consent (25/39); 12.5% of articles from the Journal of the Canadian Chiropractic Association involved human subject research (5/40), of which 80% reported ethics board approval (4/5) and 40% reported informed consent (2/5); and 37.5% of articles published in Chiropractic and Osteopathy involved human subject research (6/16), of which 50% reported ethics board approval (3/6) and 17% reported informed consent (1/6). CONCLUSION: Overall, most articles reported ethics approval, and more than half reported consent. This was harmonious with research on this topic from other disciplines. This situation indicates a need for continued quality improvement and for better instruction and dissemination of information on these issues to researchers, to manuscript reviewers, to journal editors, and to the readers. PMID- 22079001 TI - Human subjects research. PMID- 22079002 TI - Cell adhesion on an artificial extracellular matrix using aptamer-functionalized PEG hydrogels. AB - The development of an artificial extracellular matrix (ECM) is important to regenerative medicine because the ECM plays complex and dynamic roles in the regulation of cell behavior. In this study, nucleic acid aptamers were applied to functionalize hydrogels for mimicking the adhesion sites of the ECM. The results showed that nucleic acid aptamers could be incorporated into polyethylene glycol (PEG) hydrogels via free radical polymerization. The incorporation of the aptamers produced only a moderate effect on the mechanical properties of the PEG hydrogels. Importantly, the results also showed that the aptamers effectively induced cell type-specific adhesion to the PEG hydrogels without affecting cell viability. The cell adhesion was a function of the aptamer concentration, the spacer length and the cell seeding time. In addition, cell adhesion to the aptamer-functionalized hydrogel could be attenuated by means of aptamer inactivation in a physiological condition. Thus, aptamer-functionalized hydrogels are promising biomaterials for the development of artificial ECMs. PMID- 22079003 TI - Preclinical pharmacokinetic, biodistribution, and anti-cancer efficacy studies of a docetaxel-carboxymethylcellulose nanoparticle in mouse models. AB - We have developed a polymer conjugate (Cellax) composed of acetylated carboxymethylcellulose (CMC), docetaxel (DTX), and PEG, designed to enhance the pharmacokinetics (PK) and antitumor efficacy of DTX. Our design placed an emphasis on nanoparticle self-assembly to protect DTX during blood transport, stability of the nanoparticle, and PEGylation to enhance PK. Compared to Taxotere, Cellax exhibited a 38.6 times greater area under the curve (AUC), and significantly lower clearance (2.5%) in PK. Less than 10% of DTX was released from Cellax in the blood circulation, indicating that Cellax were stable during blood transport. Cellax reduced non-specific distribution of DTX to the heart, lung and kidney by 48, 90, and 90%, respectively, at 3 h, compared to Taxotere. The uptake of Cellax at 3 h in the liver and spleen was high (15-45 MUg DTX/g) but declined rapidly to <10 MUg DTX/g in 24 h, and induced no measurable toxicity at 170 mg DTX/kg. Taxotere, on the other hand, displayed non-specific uptake in all the examined normal tissues and induced significant apoptosis in the lung and kidney at 40 mg DTX/kg. The tumor uptake of Cellax was 5.5-fold more than that by Taxotere and the uptake occurred within 3 h after injection and persisted for 10 days. The conjugate exhibited enhanced efficacy in a panel of primary and metastatic mouse tumor models. These results clearly demonstrated that Cellax improved the pharmacokinetics, biodistribution and efficacy of DTX compared to Taxotere with reduced toxicity. PMID- 22079004 TI - In vivo treatment of tumors using host-guest conjugated nanoparticles functionalized with doxorubicin and therapeutic gene pTRAIL. AB - The combination of gene therapy and chemotherapy may increase the therapeutic efficacy in the treatment of patients. In this work, the anti-cancer drug Dox and therapeutic gene pTRAIL-loaded host-guest co-delivery system was assayed for the possibility of in vivo synergistically treating tumors. The introduced Dox could act as an auxiliary component to human tumor necrosis factor-related apoptosis inducing ligand-encoding plasmid gene pTRAIL. Such delivery system possessed the good ability of in vivo retention of chemotherapeutic drugs, achieved good therapeutic effects in the inhibition of tumor growth and significantly prolonged the survival time of tumor-bearing mice. With the efficient ability to co-deliver drug and gene, such host-guest assembly should have great potential applications in cancer therapy. PMID- 22079005 TI - Impact of processing parameters on the haemocompatibility of Bombyx mori silk films. AB - Silk has traditionally been used for surgical sutures due to its lasting strength and durability; however, the use of purified silk proteins as a scaffold material for vascular tissue engineering goes beyond traditional use and requires application-orientated biocompatibility testing. For this study, a library of Bombyx mori silk films was generated and exposed to various solvents and treatment conditions to reflect current silk processing techniques. The films, along with clinically relevant reference materials, were exposed to human whole blood to determine silk blood compatibility. All substrates showed an initial inflammatory response comparable to polylactide-co-glycolide (PLGA), and a low to moderate haemostasis response similar to polytetrafluoroethylene (PTFE) substrates. In particular, samples that were water annealed at 25 degrees C for 6 h demonstrated the best blood compatibility based on haemostasis parameters (e.g. platelet decay, thrombin-antithrombin complex, platelet factor 4, granulocytes-platelet conjugates) and inflammatory parameters (e.g. C3b, C5a, CD11b, surface-associated leukocytes). Multiple factors such as treatment temperature and solvent influenced the biological response, though no single physical parameter such as beta-sheet content, isoelectric point or contact angle accurately predicted blood compatibility. These findings, when combined with prior in vivo data on silk, support a viable future for silk-based vascular grafts. PMID- 22079006 TI - Recombinant spider silk particles for controlled delivery of protein drugs. AB - The engineered and recombinant spider silk protein eADF4(C16) has been shown to be a promising biomaterial for the use as drug delivery system. In previous studies, eADF4(C16) particles were loaded with low molecular weight drugs exhibiting a positive net-charge and sufficient hydrophobicity. Here, we demonstrate that also macromolecular drugs like proteins can be loaded on eADF4(C16) particles. Using lysozyme as a model protein, remarkably high loading of up to 30% [w/w] was feasible and high loading efficiencies of almost 100% were obtained. Furthermore, using confocal laser scanning microscopy, it is demonstrated that fluorescently labeled lysozyme is not only adsorbed to the negatively charged particles' surface, but also diffusing into the matrix of eADF4(C16) particles. The release of lysozyme is shown to be dependent on the ionic strength and pH of the release medium. To improve the long-term stability of eADF4(C16) containing dispersions, lyophilization is shown as a suitable tool. Disaccharides (sucrose, trehalose) and mannitol served as stabilizers to prevent aggregation and/or particle degradation during freeze-drying. The slowly biodegradable eADF4(C16) particles are a promising new particulate drug carrier system for the delivery of susceptible drugs like therapeutic proteins. PMID- 22079007 TI - Influence of cell culture configuration on the post-cryopreservation viability of primary rat hepatocytes. AB - Cryopreservation has been identified as a necessary barrier to overcome in the production of tissue engineered products for clinical application. Liver engineering and bioartificial liver assisting devices are on the forefront of tissue engineering research due to its high demand and clinical potential. In this study we propose that the cryopreservation of primary mammalian hepatocytes yields better results when these cells are in a tissue-like culture configuration since cell attachment is essential for cell survival in this cell type. We used two different tissue-engineered culture configurations: monolayers and spheroid culture; and two different concepts of cryopreservation, namely vitrification and freezing. Cell suspensions were also cryopreserved using both approaches and results were compared to the engineered cultures. Both engineered configurations and suspension were cryopreserved using both conventional freezing (cooling at 1 degrees C/minute using 10% DMSO in foetal calf serum) and vitrification (using 40% ethylene glycol 0.6 m sucrose supplemented with 9% Ficoll). These two approaches differ on the degree of mechanical stress they inflict on the material to be cryopreserved. The maintenance of cell-to-cell and the integrity of the actin cytoskeleton were assessed using scanning electron microscopy and immunohistochemistry respectively. Results showed that while there was no significant difference between the degree of integrity shown between vitrified and control engineered cultures, the same did not happen to the frozen engineered constructs. The disruption of the cytoskeletal structure correlated with increased levels of apoptotic markers. With cryopreserved suspensions there was evidence of disruption of the cytoskeletal structure. This study concluded that cell-to-cell contact is beneficial in the maintenance of viability post cryopreservation and that the vitrification approach was far superior to those of conventional freezing when applied to 2D and 3D hepatocyte based engineered cultures. PMID- 22079008 TI - Glycosaminoglycan (GAG) binding surfaces for characterizing GAG-protein interactions. AB - Glycosaminoglycans play an important role in tissue organisation through interactions with a diverse range of proteins, growth factors and other chemokines. In this report, we demonstrate the GAG-binding 'fingerprint' of two important GAG-binding proteins - osteoprotogerin and TIMP-3. The technique uses a straightforward method for attaching GAGs to assay surfaces in a non-covalent manner using plasma polymerization that leaves the adsorbed GAG able to participate in subsequent ligand binding. We show that OPG and TIMP-3 bind preferentially to different GAGs in a simple ELISA and that this binding does not correlate directly with simple GAG properties such as degree of sulfation. The methods outlined in this report can be easily applied to tissue engineering scaffolds in order to exploit the potential of surface-bound GAGs in influencing the structure of engineered tissues. PMID- 22079009 TI - Parental duties and prenatal screening: does an offer of prenatal screening lead women to believe that they are morally compelled to test? AB - BACKGROUND: in debates around prenatal screening, it is frequently argued that responsible parenthood implies the acquisition of all available medical information about the health of a fetus, and use of this information to benefit the future child. OBJECTIVE: to analyse whether an offer of a prenatal test leads women to believe that they are morally obliged to control the health of their fetus. DESIGN: a substudy within a randomised controlled trial (RCT) aimed to assess the decision-making process of women when confronted with an offer of a prenatal screening test. PARTICIPANTS: 111 women participating in an RCT were retrospectively asked their views on the meaning of testing within their parental duties. FINDINGS: testing was described as a personal option that goes beyond the normal parental responsibilities. Participants did not believe that they ought to control the health of the fetus or to avoid disability. A duty to test was only reported when the birth of a disabled child would have a negative impact on family life. CONCLUSION: women's accounts suggest that two main factors are involved in making testing morally obligatory: (1) the woman's views on her moral duties to her family; and (2) the expected burden of a disabled child on the well being of the family. A family-centred approach would be more suitable to assess the moral imperative character of testing than women's ethical views about their moral duties towards their unborn child. IMPLICATIONS: a test offer should not be limited to communication of the characteristics of screening and the meaning of the test results. In helping women to assess the meaning of testing within their parental duties, counselling should include the family situation in which women have to decide, the women's expectations about living with a child with Down's syndrome or any other disability, and the women's views on their commitments towards their family. PMID- 22079010 TI - An exploration of clinical decision-making among students and newly qualified midwives. AB - OBJECTIVE: to explore how midwifery students and newly qualified midwives learnt to make clinical decisions. DESIGN: an ethnographic approach was taken. Data collection methods included: 3 focus groups, 15 observations of practice and 27 interviews. The data analysis followed the principles of category and theme identification as described by Garner (1991) and Ely et al. (1997). Vignettes were created to represent the findings. SETTINGS AND PARTICIPANTS: the study took place in the School of Nursing Sciences and 2 NHS Trusts in the Eastern region of England. Participants included 36 midwifery students, 5 midwives who had been qualified for less than 1 year and 12 midwifery mentors. KEY CONCLUSIONS: decision-making was learnt primarily by working alongside midwifery mentors and through situated learning in practice. Decision-making was not necessarily a solo activity, it was common for midwives to use each other as a resource, which established there was a social dimension to midwifery decision-making. Learners had to navigate through workplace culture, which consisted of: the practices shared by some midwives and not others, covert rules of practice, midwifery and institutional authoritarianism. IMPLICATIONS FOR PRACTICE: learners need to work with mentors who actively encourage participation in decision-making and provide discussion and feedback on decision-making abilities. When a staged and active approach to decision-making is not provided this may have negative implications on the transition to qualified practitioner. PMID- 22079011 TI - Hypnosis: a twilight zone of the top-down variety Few have never heard of hypnosis but most know little about the potential of this mind-body regulation technique for advancing science. AB - An early form of psychotherapy, hypnosis has been tarnished by a checkered history: stage shows, movies and cartoons that perpetuate specious myths; and individuals who unabashedly write 'hypnotist' on their business cards. Hypnosis is in the twilight zone alongside a few other mind-body exemplars. Although scientists are still unraveling how hypnosis works, little is mystical about this powerful top-down process, which is an important tool in the armamentarium of the cognitive scientist seeking to unlock topical conundrums. PMID- 22079012 TI - Implementing the Mental Health Act 2007 in British general practice: Lessons from Ireland. AB - Changes in mental health legislation (e.g. Mental Health Act 2007 in England and Wales, Mental Health Act 2001 in Ireland) have generally improved adherence to international human rights standards, but also present challenges to primary care providers. When mental health legislation was substantially reformed in Ireland, 62.9% of general practitioners (GPs) felt the new legislation was not user friendly. Majorities of GPs who felt the legislation affected their practice reported increased workloads (85%) and various other difficulties (53%). GPs who had received training about the legislation were more likely to find it user friendly (43% versus 30.9%), and informal training (e.g. from colleagues) was just as likely as formal training to be associated with a GP finding it user friendly. With similar changes to mental health legislation being introduced in England and Wales, it is significant that informal training is just as good as formal training in helping GPs work with new mental health legislation. PMID- 22079013 TI - Crosstalk between NDR kinase pathways coordinates cell cycle dependent actin rearrangements. AB - Regulation of cytoskeletal remodeling is essential for cell cycle transitions. In fission yeast two NDR kinase signaling cascades, MOR and SIN, regulate the actin cytoskeleton to promote polarized growth during interphase and cytokinesis respectively. Our understanding of how these signaling pathways are coordinated to assist transition between the two cell-cycle stages is limited. Here, we review work from our laboratory, which reveals that cross talk between the SIN and MOR pathways is required for inhibition of interphase polarity programs during cytokinesis. Given the conservation of NDR kinase signaling pathways, our results may define general mechanisms by which these pathways are coordinated in higher organisms. PMID- 22079014 TI - Exploring and optimising maternal and infant nutrition in North West Pakistan. AB - OBJECTIVES: the aim of this study was to explore and contextualise meanings, beliefs and practices surrounding maternal and infant nutrition in North West Pakistan and to use the findings to inform the development of a nutritional improvement programme adapted to local needs. DESIGN: the Context-Mechanism Outcome framework was used to gather contextual data, formulate questions and conduct focus groups to inform the design of a culturally appropriate nutritional health programme with the overall goal of improving practices related to maternal and infant nutrition. Two focus groups were conducted with the team of local lady health workers (n=16), one prior to implementing a nutritional improvement programme and one 6 months after implementation. SETTINGS: the study was conducted in communities surrounding and served by the Emergency Satellite Hospital (ESH) in Nahaqi in Khyber Pakhtunkhawa (KP) (formally known as the Northwest Frontier Province), Pakistan. FINDINGS: poverty and specific cultural practices impeded the achievement of optimum maternal and infant nutrition. A nutrition support programme was implemented; it involved cookery demonstration kitchens and free food supplements, coupled with nutrition and health-care information-giving for pregnant and lactating women. Focus group discussions revealed that women had positive perceptions of the impact of the nutritional health improvement programme, feeling that knowledge and practices were enhanced. However, structural and cultural factors continued to have a powerful influence on their practices. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: this study highlights that despite structural, cultural and practical barriers, a culturally sensitive health improvement programme has the potential to enhance maternal and infant nutritional practices. However, we should not underestimate the powerful influence of poverty and culturally embedded norms upon women's decisions and practices. PMID- 22079015 TI - An exploratory study of traditional birthing practices of Chinese, Malay and Indian women in Singapore. AB - OBJECTIVES: to explore the traditional birthing practices of Singaporean women. RESEARCH DESIGN: a qualitative study using a phenomenological approach. Data were collected using individual interviews, which were audio-recorded and transcribed verbatim. Colaizzi's phenomenological method was used to analyse the data. SETTING: obstetric outpatient clinics in a tertiary hospital in Singapore. PARTICIPANTS: a purposive sample of 30 women, 1-3 months postpartum. FINDINGS: two broad themes emerged-following tradition and challenging tradition. KEY CONCLUSIONS: Singaporean women experiencing pregnancy and childbirth follow tradition through the influence of their mother and mother-in-law and because of worry over consequences that may result if they do not. Tradition is also challenged through the modification or rejection of traditional practices and changing family roles and expectations. IMPLICATIONS: health professionals need to provide accurate information on traditional birthing practices and scientific evidence to support or refute such practices with the aim of preventing women from adhering to practices that are hazardous to them and the baby. PMID- 22079016 TI - Bugs and battles during the American Civil War. PMID- 22079017 TI - Genetics for the general internist. AB - The internist's goal is to determine a patient's disease risk and to implement preventative interventions. Genetic evaluation is a powerful risk assessment tool, and new interventions target previously untreatable genetic disorders. The purpose of this review is to educate the general internist about common genetic conditions affecting adult patients, with special emphasis on diagnoses with an effective intervention, including hereditary cancer syndromes and cardiovascular disorders. Basic tenets of genetic counseling, complex genetic disease, and management of adults with genetic diagnoses also are discussed. PMID- 22079018 TI - Systematic review of guidelines on peripheral artery disease screening. AB - BACKGROUND: Peripheral artery disease (PAD) screening may be performed to prevent progression of PAD or future cardiovascular disease in general. Recommendations for PAD screening have to be derived indirectly because no randomized trials comparing screening versus no screening have been performed. We performed a systematic review of guidelines to evaluate the value of PAD screening in asymptomatic adults. METHODS: Guidelines in English published between January 1, 2003 and January 20, 2011 were retrieved using MEDLINE, CINAHL, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the G-I-N International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on PAD screening, were included. Two reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was validated by a second reviewer. RESULTS: Of 2779 titles identified, 8 guidelines were included. AGREE scores varied from 33% to 81%. Five guidelines advocated PAD screening, others found insufficient evidence for PAD screening or were against it. Measurement of the ankle-brachial index (ABI) was generally recommended for middle-aged populations with elevated cardiovascular risk levels. Those identified as having PAD are reclassified as high risk, warranting intensive preventive interventions to reduce their risk of a cardiovascular event. The underlying evidence mainly consisted of studies performed in patients with established PAD. A meta-analysis that evaluated ABI testing in the context of traditional cardiovascular risk assessment was interpreted differently. CONCLUSIONS: Recommendations on PAD screening vary across current guidelines, making the value of PAD screening uncertain. The variation seems to reflect lack of studies that show added value of detection of early PAD beyond expectant management and traditional risk assessment. PMID- 22079019 TI - Preoperative thienopyridine use and outcomes after surgery: a systematic review. AB - BACKGROUND: Although studies have demonstrated excess risk of ischemic events if aspirin is withheld preoperatively, it is unclear whether preoperative thienopyridine use influences postoperative outcomes. METHODS: We conducted a systematic review of 37 studies (31 cardiac and 6 noncardiac surgery, 3 randomized, 34 observational) comparing postoperative outcomes in patients who were versus were not exposed to thienopyridine in the 5 days before surgery. RESULTS: Exposure to thienopyridine in the 5 days preceding surgery (compared with no exposure) was not associated with any reduction in postoperative myocardial infarction (23 studies, 12,872 patients, 3.4% vs 3.0%, odds ratio [OR] 0.98; 95% confidence interval [CI], 0.72-1.34), but was associated with increased risks of stroke (16 studies, 10,265 patients, 1.9% vs 1.4%, OR 1.54; 95% CI, 1.08 2.20), reoperation for bleeding (32 studies, 19,423 patients, 4.3% vs 1.8%, OR 2.62; 95% CI, 1.96-3.49), and all-cause mortality (28 studies, 22,990 patients, 3.7% vs 2.6%, OR 1.38; 95% CI, 1.13-1.69). Results were identical when analyses were restricted to long-term users of thienopyridines who continued versus held the medication in the 5 days before surgery. Although all associations were similar in direction for the subset of patients undergoing noncardiac surgery, 97% of the outcome data in this meta-analysis came from cardiac surgery trials. CONCLUSIONS: These data support withholding thienopyridines 5 days before cardiac surgery; there was insufficient evidence to make definitive recommendations for elective noncardiac surgery although the direction and magnitude of associations were similar. PMID- 22079020 TI - Use of anti-infective drugs during pregnancy and the risk of preterm birth. PMID- 22079022 TI - Redotex(r) revisited: intentional overdose with an illegal weight loss product. PMID- 22079021 TI - T lymphocyte recruitment into renal cell carcinoma tissue: a role for chemokine receptors CXCR3, CXCR6, CCR5, and CCR6. AB - BACKGROUND: Evidence suggests that some patients with renal cell carcinoma (RCC) respond to immunomodulatory therapies that activate T lymphocytes. A prerequisite for effective T cell therapy is efficient targeting of effector T cells to the tumour site, yet the molecular basis of T cell recruitment to RCC is unknown. Furthermore, some T cells that naturally infiltrate this cancer are regulatory T cells (Tregs) that may suppress antitumour immune responses. OBJECTIVE: Determine the mechanisms of effector and regulatory T cell recruitment to RCC to allow targeted therapy that promotes local anti-tumour immunity. DESIGN, SETTING, AND PARTICIPANTS: Tumour-infiltrating and peripheral blood T cells were collected from 70 patients undergoing nephrectomy for RCC. MEASUREMENTS: T cells were analysed by multicolour flow cytometry for expression of 19 chemokine receptors and 7 adhesion molecules. Receptors that were expressed at higher levels on tumour-infiltrating lymphocytes (TILs) compared with matched peripheral blood lymphocytes (PBLs) were analysed further for their ability to mediate migration responses in TILs and for expression of corresponding ligands in tumour tissue. RESULTS AND LIMITATIONS: Three chemokine receptors-CCR5, CXCR3, and CXCR6-were significantly overexpressed on TILs compared with matched PBLs (n=16 cases) and were capable of promoting migration in vitro. Their corresponding ligands CCL4-5, CXCL9-11, and CXCL16 were all detected in RCC tissue. However, since they were present in all cases studied, it was not possible to correlate ligand expression with levels of T cell infiltration. Foxp3(+) Tregs were enriched within TILs compared with matched PBLs and expressed high levels of CCR5, CXCR3, and CXCR6, as well as CCR6, the ligand for which (CCL20) was detectable in RCC tissue. CONCLUSIONS: Our data support a role for CCR5, CXCR3, and CXCR6 in the selective recruitment of T cells into RCC tissue and, together with CCR6, in the recruitment of Tregs. PMID- 22079023 TI - Burnout syndrome. PMID- 22079024 TI - A case of sudden, painless, and persistent urinary incontinence. AB - BACKGROUND: Urinary incontinence is not a common emergency department (ED) complaint, and it is hard to imagine that a case involving this complaint could turn out to be interesting. We report the case of a patient who presented with the complaint of sudden onset of painless urinary incontinence for 1 day, who had an unexpected diagnosis. OBJECTIVES: To describe a case of incontinence with an unexpected diagnosis and to review the various causes of incontinence. CASE REPORT: A 52-year-old woman with a history of kidney stones recently treated with lithotripsy, nephrostomy tubes, and ureteral stents, presented to the ED complaining of new-onset incontinence. The patient had awakened on the morning of presentation with urinary incontinence that persisted throughout the day. On examination she had normal vital signs, and other than a functioning nephrostomy tube, she had a normal examination. In addition to a urinalysis, a KUB (kidney, ureter, and bladder) X-ray study was performed, which showed that her recently placed right ureteral stent had migrated from its original location into the urethra. The stent was found by the urologist protruding from the urethral meatus and removed without difficulty. The patient's incontinence resolved immediately after the stent was removed. CONCLUSION: Emergency physicians frequently see patients with ureteral stents, but may not be aware of how frequently those stents can migrate or malfunction. Our experience suggests that radiologic determination of stent location may be helpful in patients who present with new onset stress or overflow incontinence. PMID- 22079025 TI - alpha-Haemoglobin stabilising protein expression is influenced by mean cell haemoglobin and HbF levels in HbE/beta-thalassaemia individuals. AB - The alpha haemoglobin stabilising protein (AHSP) acts as a molecular chaperone for alpha-globin by stabilising nascent alpha-globin before transferring it to waiting free beta-globin chains. Binding of AHSP to alpha-globin renders alpha globin chemically inert whereby preventing it from precipitating and forming reactive oxygen species byproducts. The AHSP has been actively studied in the recent years, particularly in its relation to beta-thalassaemia. Studies have shown that AHSP is a modifier in beta-thalassaemia mice models. However, this relationship is less established in humans. Studies by some groups showed no correlation between the AHSP haplotypes and the severity of beta-thalassaemia, whereas others have shown that certain AHSP haplotype could modify the phenotype of beta-thalassaemia intermedia patients. We investigated the expression of AHSP in relation to selected demographic data, full blood count, HPLC results, HbE/beta-thalassaemia genotype, Xmn-1 Ggamma polymorphism, alpha-globin, beta globin and gamma-globin expression. We found that AHSP expression was significantly correlated to mean cell haemoglobin level, HbF %, alpha-globin, beta-globin and excess alpha-globin expression. We concluded that AHSP could be a secondary compensatory mechanism in red blood cells to counterbalance the excess alpha-globin chains in HbE/beta-thalassaemia individuals. PMID- 22079026 TI - Novel 2-(2-(4-aryloxybenzylidene) hydrazinyl)benzothiazole derivatives as anti tubercular agents. AB - A series of structurally novel, substituted 2-(2-(4-aryloxybenzylidene) hydrazinyl)benzothiazole derivatives incorporating 2-hydrazinyl benzothiazole and 4-(aryloxy)benzaldehyde were designed and synthesized using molecular hybridization approach. All the synthesized compounds exhibited promising activity (MIC 1.5-29.00MUg/ml) against Mycobacteriumtuberculosis H37Rv strains of using REMA. Five of the evaluated compounds exhibit MIC <3.0MUg/ml. Compound (E) 6-chloro-2-(2-(4-(2,4-dichlorophenoxy)benzylidene)hydrazinyl) benzothiazole showed MIC of 1.5MUg/ml. Thus, this compound could act as a potential lead for further development of new anti-tubercular drugs. PMID- 22079027 TI - Conformationally restricted analog and biotin-labeled probe based on beauveriolide III. AB - A conformationally restricted oxazoline analog 7 was designed on the basis of a SAR study of beauveriolide III (2) and its analogs reported previously. Conformational analysis by molecular mechanics calculation suggested that the three side chains of 7 mostly occupy the same spaces as those of 2. The analog 7 was synthesized by peptide coupling of the d-cyclohexylglycine-containing ester 11 and d-Ser-containing dipeptide 12, macrolactamization, and cyclodehydration of 6 for the construction of an oxazoline ring. The bicyclic 7 exhibited potential inhibitory activity for cholesteryl ester synthesis similar to that by 2. These results revealed biologically important 3D spaces of the three side chains in inhibitory activity for cholesteryl ester synthesis. In addition, we accomplished the synthesis of a biotin-labeled probe 8 by copper-catalyzed (3+2) cycloaddition of a biotin-containing alkyne 16 and azido-containing beauveriolide analog 15 prepared from 6. PMID- 22079028 TI - Facile synthesis of 1,2,3-triazole analogs of SGLT2 inhibitors by 'click chemistry'. AB - Novel analogs of SGLT2 inhibitors containing the 1,2,3-triazole motif were designed and synthesized for urinary glucose excretion evaluation. The C glucosides with triazole aglycone can be easily constructed by click chemistry. Most of the synthesized compounds increased urinary glucose excretion and demonstrated inhibition of glucose transport. PMID- 22079029 TI - [Contraception news]. AB - Although contraception is widely available in France, contraceptive failure remains high. However a number of modifications in contraceptive methods have been developed and should help reduce contraceptive failure. Among those, information and improvement of access to contraception are very important. Recent advances in contraceptive practice have also contributed to improve clinical tolerance and subsequently compliance. Finally, emergency contraception has evolved as well. PMID- 22079030 TI - Endemic sheep scab: risk factors and the behaviour of upland sheep flocks. AB - Since the deregulation of sheep scab in 1992, the number of scab outbreaks per year in the UK has increased rapidly; there has been an estimated 60-fold increase in outbreak incidence between 1992 and 2007. How best to focus management or eradication efforts has therefore been an issue of ongoing debate. Previous work has shown that scab outbreaks occur repeatedly on some farms whereas others never or rarely experience outbreaks. Here, to consider why this pattern occurs, and to quantify the risk of scab associated with different husbandry practices, face-to-face interviews with farmers at 16, randomly selected, repeat-outbreak farms and 16 matched farms with no or little history of scab over the previous 10 years, were used to identify associated risk factors. This showed that farms using common grazing were at significantly higher risk of infestation than farms not using common grazing, as were farms that had direct contact with neighbours' sheep and that had neighbours with scab. To further demonstrate the risk of common grazing, a survey of sheep on one common in south Wales showed that there was significant mixing of sheep from three farms, highlighting the potential for scab transmission between flocks. Common grazing, associated with upland regions, would appear to be the largest single obstacle to effective national scab control in the UK. The results suggest that a cost effective approach to scab control may be to consider upland and lowland farms as separate epidemiological systems, with upland regions requiring a co-ordinated, systematic approach to achieve any significant management of the problem. In contrast, on lowland farms outbreaks are already largely contained effectively through good biosecurity and treated on a case-by-case basis if they occur. PMID- 22079031 TI - How do supervising surgeons evaluate guidance provided in the operating room? AB - BACKGROUND: This study explored the amount of guidance provided to residents in the operating room (OR) and the relationship of OR guidance with postgraduate year (PGY) and operative performance rating (OPR). METHODS: We used OPR instruments to collect data from supervising surgeons after each performance. External expert raters blindly rated the amount of guidance for 5 videotaped performances. RESULTS: Three hundred sixty-eight performances were analyzed for 5 procedures performed by 26 residents with 16 supervising surgeons over 6 months. Guidance ratings varied with procedure, individual supervising surgeons varied in the amount of guidance reported, the amount of guidance decreased as residents' PGY level increased, and the correlation between guidance rating and overall performance was .62. In comparison cases, most supervising surgeons underestimated the amount of guidance provided. CONCLUSIONS: Controlling for the amount of supervising surgeon guidance has important implications for training and evaluation as we strive to prepare residents to practice independently. PMID- 22079032 TI - Assessment of the learning curve for pancreaticoduodenectomy. AB - BACKGROUND: Experience with the Whipple procedure has been associated with improved outcomes, but the learning curve for this complex procedure is not well defined. METHODS: Outcomes with 162 consecutive Whipple procedures during the 1st 11.5 years of practice was documented in a prospective database. A period of low (<=11/y) and high (>=23/y) case volume was compared using the Wilcoxon rank-sum test and Fisher exact test. RESULTS: With low case volume, blood loss was higher (800 vs 400 mL, P = .001), more patients were transfused (44% vs 18%, P = .027), there were more complications (58% vs 46%, P = .0337), and a longer length of stay (10 vs 7 days, P = .006). There was only 1 mortality (.7%). CONCLUSIONS: Frequent repetition of the Whipple procedure is associated with an improvement in quantifiable quality benchmarks, and improvement continues with extensive experience. However, with proper training and the right environment, this procedure can be performed during the learning curve with acceptable outcomes. PMID- 22079033 TI - A preliminary review of a pilot curriculum to teach open surgical skills during general surgery residency with initial feedback. AB - INTRODUCTION: The aim of this study is to provide a preliminary review of a pilot curriculum to teach open surgical skills during general surgery residency and obtain initial feedback. DATA SOURCE: The general surgery residency program introduced an open surgical skills training curriculum in 2009. The skills sessions are undertaken under the guidance of the faculty. An annual survey was distributed to the residents and faculty to obtain their feedback. CONCLUSIONS: A total of 50 sessions were conducted over the last 2 years. Ninety-five percent of the residents perceived this educational activity to be above average to exceptional with nearly 70% rating it as exceptional. Sixty-three percent of the faculty perceived it as above average to exceptional, with nearly 40% rating it as exceptional. The open surgical skills training curriculum was rated as the most educational activity in the program by residents and faculty alike. PMID- 22079034 TI - Sleep deprivation increases cognitive workload during simulated surgical tasks. AB - BACKGROUND: There have been conflicting reports of the effects of modest sleep deprivation on surgical skills. The aim of this study was to assess the effects of a 24-hour call shift on technical and cognitive function, as well as the ability to learning a new skill. METHODS: Thirty-one students trained to expert proficiency on a virtual reality part-task trainer. They then were randomized to either a control or sleep-deprived group. On the second testing day they were given a novel task. Fatigue was assessed using the Epworth Sleepiness Scale. The National Aeronautics and Space Administration-Task Load Index was used to assess cognitive capabilities. RESULTS: There was no difference between the control and sleep-deprived groups for performance or learning of surgical tasks. Subjectively, the Epworth Sleepiness Scale showed an increase in sleepiness. The National Aeronautics and Space Administration-Task Load Index showed an increase in total subjective mental workload for the sleep-deprived group. CONCLUSIONS: Sleep-deprived subjects were able to complete the tasks despite the increased workload, and were able to learn a new task proficiently, despite an increase in sleepiness. PMID- 22079035 TI - Studies of the myocardial uptake and excretion mechanisms of a novel 99mTc heart perfusion agent. AB - INTRODUCTION: (99m)Tc-TMEOP is a novel heart perfusion radiotracer exhibiting high initial and persistent heart uptake associated with rapid blood and liver clearance. This study aimed at determining the mechanisms of myocardial localization and fast liver clearance of (99m)Tc-TMEOP. METHODS: Subcellular distribution of (99m)Tc-TMEOP was determined in excised rat heart tissue by differential centrifugation. The effect of cyclosporin A on the pharmacokinetic behaviour of (99m)Tc-TMEOP was evaluated by both ex vivo biodistribution and in vivo planar imaging studies. RESULTS: Subcellular distribution studies showed that more than 73% of (99m)Tc-TMEOP was associated with the mitochondrial fraction. Comparison with subcellular distribution of (99m)Tc-sestamibi showed no significant difference in the mitochondrial accumulation between the two tracers. Biodistribution studies in the presence of cyclosporin A revealed an increase in kidneys and liver uptake of (99m)Tc-TMEOP, suggesting the involvement of multidrug resistance transporters in determining its pharmacokinetic profile. CONCLUSIONS: The heart uptake mechanism of (99m)Tc-TMEOP is similar to that of the other reported monocationic (99m)Tc cardiac agents and is associated with its accumulation in the mitochondria. Cyclosporin A studies indicate that the fast liver and kidney clearance kinetics is mediated by P-glycoprotein (Pgp), supporting the potential interest of this radiotracer for imaging Pgp function associated with multidrug-resistant tumours. PMID- 22079036 TI - Combining dose and injection volume for good performance of a specific radiopharmaceutical for sentinel node detection. AB - INTRODUCTION: The aim of this work was to quantify the effects of injection volume at different technetium-99m specific radiotracer doses on its lymphatic movement in animal model. PROCEDURES: Effects of injection volume (50, 100 MUl) at different doses (0.05, 0.135, 0.22 nmol) on popliteal node (PN) detection were studied in rats. The radiotracer under study was (99m)Technetium-cysteine-mannose dextran conjugate (30 kDa). RESULTS: At 0.05 nmol dose, higher PN uptake was observed at 50 MUl injection volume (2.6 fold increase). Conversely, at 0.135 nmol dose, an increase of radiotracer retention in PN was achieved at 100 MUl volume, 78% higher than 50 MUl. However, at 0.22 nmol dose, the injection volume changes did not influence on the PN uptake. Considering as suitable radiotracer performance: high PN uptake and extraction, better combinations were 0.05 nmol/50 MUl, 0.135 nmol/100 MUl, 0.22/50 MUl. CONCLUSION: Suitable performances could be reached by proper combinations of dose, injection volume and concentration for a specific radiotracer used in sentinel lymph node detection. PMID- 22079037 TI - [18F]-fluoroestradiol quantitative PET imaging to differentiate ER+ and ERalpha knockdown breast tumors in mice. AB - INTRODUCTION: The purpose of this study was to develop a noninvasive model in tumor-bearing mice to investigate the use of 16alpha-[(18)F]fluoro-17beta estradiol (FES) positron emission tomography (PET) imaging as a tool to discriminate between tumors having different estrogen receptor (ER) alpha status. METHODS: MC7-L1 and MC4-L2 murine mammary adenocarcinoma cell lines (ER+) received a small hairpin RNA targeting the ERalpha gene by lentiviral infection. In vitro assessment of ERalpha levels of the new cell lines (MC7-L1 and MC4-L2 ERalpha-knockdown; ERalphaKD), compared to the parental cell lines, was performed by immunoblotting (-75% ERalpha protein) and binding assays (-50% estrogen binding). These cell lines were implanted subcutaneously in Balb/c mice and allowed to grow up to a volume of at least 20 mm(3). FES and [(18)F]fluorodeoxyglucose (FDG) PET images were acquired to measure FES and FDG uptake in the various tumors. RESULTS: FES uptake as assessed by PET imaging was 1.06+/-0.21 percent injected dose per gram of tissue (%ID/g) for MC7-L1 tumors and 0.47+/-0.08 %ID/g for MC7-L1 ERalphaKD tumors. MC4-L2 tumors had a FES uptake of 1.03+/-0.30 %ID/g, whereas its ERalphaKD equivalent was 0.51+/-0.19 %ID/g. Each ERalphaKD tumor had a significantly lower %ID/g value, by ~50%, than its ER+ counterpart. Biodistribution studies confirmed these findings and gave %ID/g values that were not significantly different from PET imaging data. FDG PET showed no significant uptake difference between the ER+ and ERalphaKD tumors, indicating that the metabolic phenotype of the ERalphaKD cell lines was not altered. CONCLUSION: FES PET imaging was able to reliably differentiate between tumors having differences in their ERalpha expression in vivo, in a mouse model. Quantitative data obtained by FES PET were in concordance with biodistribution studies and in vitro assays. It is concluded that FES PET imaging can likely be used to monitor subtle ER status changes during the course of hormone therapy. PMID- 22079039 TI - Combination of nitric oxide stimulation with high-dose 18F-FDG promotes apoptosis and enhances radiation therapy of endothelial cells. AB - INTRODUCTION: High-dose (18)F-FDG can provide targeted nuclear therapy of cancer. Endothelial cell injury is a key determinant of tumor response to radiotherapy. Here, we tested the hypothesis that activation of endothelial cell glycolytic metabolism with nitric oxide can enhance the therapeutic effect of high-dose (18)F-FDG. METHODS: Calf pulmonary artery endothelial (CPAE) cells were treated with graded doses of (18)F-FDG. Glycolysis was stimulated by 24 h of exposure to the nitric oxide donor, sodium nitroprusside (SNP). Cell viability was assessed by MTT and clonogenic assays. Apoptosis was evaluated by ELISA of cytosolic DNA fragments and Western blots of cleaved caspase-3. RESULTS: SNP stimulation (0.1 and 1 mM) augmented CPAE cell (18)F-FDG uptake to 2.6- and 4.6-fold of controls without adverse effects. Treatment with 333 MUCi/ml (18)F-FDG alone reduced viable cell number to 35.4% of controls by Day 3. Combining 0.1 mM SNP stimulation significantly enhanced the killing effect, reducing cell numbers to 19.2% and 39.2% of controls by 333 and 167 MUCi/ml of (18)F-FDG, respectively. (18)F-FDG also suppressed clonogenic survival to 80.8% and 43.2% of controls by 83 and 167 MUCi/ml, which was again intensified by SNP to 59.7% and 21.1% of controls. The cytotoxic effect of (18)F-FDG was attributed to induction of apoptosis as shown by increased cytosolic fragmented DNA and cleaved caspase-3 levels (26.4% and 30.7% increases by 167 MUCi/ml). Combining SNP stimulation significantly increased both of these levels to 1.8-fold of control cells. CONCLUSION: High-dose (18)F-FDG combined with nitric oxide-stimulated glycolysis is an effective method to inhibit endothelial cell survival and promote apoptosis. These results suggest a potential role of this strategy for targeted radiotherapy of angiogenic vasculature. PMID- 22079038 TI - [11C]Acetate rest-stress protocol to assess myocardial perfusion and oxygen consumption reserve in a model of congestive heart failure in rats. AB - This study describes an [(11)C]acetate rest-stress method to obtain an indirect estimate of myocardial blood flow (MBF) and myocardial oxygen consumption (MVO(2)) in rats. Doxorubicin cardiotoxicity was used to test the usefulness of this approach for the assessment of congestive heart failure. METHODS: [(11)C]Acetate rest-stress studies have been used in clinical research to assess the capacity of the coronary arteries to respond to stress. In this article, we used this approach to assess the cardiotoxicity of doxorubicin in a rat model. The method was first validated in a group of healthy rats and then used to follow the effect of doxorubicin chemotherapy on cardiac function. The effect of doxorubicin on myocardial perfusion and oxygen consumption reserve was measured at rest and under dobutamine stimulation. RESULTS: Validation of the protocol showed a good correlation between the MBF and MVO(2) (r(2)=.68). The doxorubicin treated group showed a significant (P=.04) decrease in cardiovascular perfusion reserve at 1.3+/-0.2 compared with the control animals at 1.6+/-0.2. Similar results were obtained for the MVO(2) reserve (treated 1.8+/-0.4 vs. controls 2.3+/-0.3; P=.02). CONCLUSIONS: We describe an [(11)C]acetate PET rest-stress protocol for the assessment of congestive heart failure in rats and its application to the follow-up of cardiotoxicity under doxorubicin chemotherapy. This is a rapid and reliable approach to the measurement of cardiac perfusion and oxygen consumption reserve that could be applied to the development of new strategies to reduce the cardiotoxicity of anthracycline. PMID- 22079040 TI - Radiohalogenated 4-anilinoquinazoline-based EGFR-TK inhibitors as potential cancer imaging agents. AB - INTRODUCTION: The overexpression of epidermal growth factor receptor (EGFR) in tumors underlines the recent interest in EGFR as attractive target for the development of new cancer imaging agents. EGFR-tyrosine kinase inhibitors (EGFR TKIs) based on the anilinoquinazoline scaffold have been explored as potential probes for EGFR imaging. However, up to now, no optimal radiotracer is available. Herein, we report the synthesis and biological evaluation of three novel halogenated 6-substituted 4-anilinoquinazoline based EGFR-TKIs. Radiosynthesis ((125)I and (18)F) of the corresponding analogues was also performed. METHODS: 6a, 6b and 8 were obtained by reaction of 6-amino-4-anilinoquinazoline (5) with 3 /4-iodobenzoyl and 4-fluorobenzoyl chlorides. Inhibition of EGFR autophosphorylation and A431 cellular proliferation were assessed by Western blot and MTT assays. (125)I-anilinoquinazolines [(125)I]6a/b were prepared via destannylation of the corresponding tributylstannyl precursors with [(125)I]NaI. Cellular uptake studies were conducted in A431 cells. Optimization of the radiosynthesis of the (18)F-anilinoquinazoline [(18)F]8 was attempted by nucleophilic substitution of the trimethylammonium- and nitro-6-substituted 4 anilinoquinazoline precursors. RESULTS: 6a, 6b and 8 were synthesized in high chemical yield. All of them are inhibitors of EGFR autophosphorylation (0.11000- to 6000-fold higher yield than those synthesized in a classical growth-associated manner. The resting cells required aerobic agitation for the maximum production. The production system also worked for other foreign enzymes but not for beta galactosidase from Aspergillus oryzae or Escherichia coli, likely suggesting an involvement of chaperons that act on a certain range of secretory proteins. PMID- 22079043 TI - The relationship of work, self-care, and quality of life in a sample of older working adults with cardiovascular disease. AB - OBJECTIVE: The study objective was to describe the self-care behaviors of adherence to medication, diet, exercise, and symptom monitoring of older workers with cardiovascular disease (CVD) and explore the relationship among job characteristics (job demands, job control, and workplace support), self-care, and quality of life. More than 3.5 million workers have CVD with significant work limitations and increased disability. Workers must meet the challenges of today's work processes that include increased stress and intense production demands while managing the complexities of their CVD. METHODS: A total of 129 workers (aged >= 45 years) with CVD completed standardized instruments about self-care (Specific Adherence Scale alpha = .74), job characteristics (Job Content Questionnaire alpha = .71), and quality of life (MacNew health-related quality of life alpha = .84). Regression analyses were used to examine relationships between variables. RESULTS: The sample had a mean age of 59.16 +/- 8.83 years, 56.3% were female, and 36.5% were African-American. Self-care behaviors varied. Most workers (71.4%) reported medication adherence, and few adhered to diet (27%), exercise (18%), or symptom monitoring (31.3%). Psychologic job demands were negatively correlated to self-care (r = -.217, P = .02). Better adherence was reported by those with workplace support (r = .313, P = .001). Job characteristics explained 22% of variance in self-care adherence behaviors. Adherence was a significant determinant of general quality of life. CONCLUSION: Because job characteristics may interfere with self-care, clinicians should assess job demands and discuss stress management with employed patients. Interventions that foster worksite programs and facilitate self-care among workers with CVD are needed. PMID- 22079044 TI - Determination of resveratrol and its sulfate and glucuronide metabolites in plasma by LC-MS/MS and their pharmacokinetics in dogs. AB - An analytical approach for the determination of trans-resveratrol (3,5,4' trihydroxy-trans-stilbene) and its glucuronide and sulfate conjugates in dog plasma by LC-MS/MS (without enzymatic hydrolysis of the conjugates) was validated to support pre-clinical toxicological and pharmacological studies. The approach required two independent sample extractions and consequent instrument runs. Samples for resveratrol determination were prepared by protein precipitation with acetonitrile; acetonitrile-methanol was used instead for resveratrol metabolites. Chromatographic separation was performed using a C18 column (30 mm * 2.0 mm) at a flow rate of 0.25 mL/min. For resveratrol the mobile phase consisted of A: 5mM ammonium acetate in water-isopropanol (98:2, v/v) and B: methanol-isopropanol (98:2, v/v) and for metabolites the mobile phase was modified as follows: A: 0.1% (v/v) formic acid in water and B: 0.1% (v/v) formic acid in acetonitrile. Total run time was 12 min for each run with retention times of about 4-5 min for all analytes. A turbo ion spray source was used operating in negative mode for resveratrol and resveratrol sulfate and in positive mode for resveratrol glucuronide. Calibration curves were linear from 5 to 1000 ng/mL for resveratrol and its glucuronide, and 10-2000 ng/mL for resveratrol sulfate. Linearity was assessed using the internal standard method for resveratrol and the external standard method for the metabolites. Method accuracy was 90-112% of the true value for all analytes with precision of 9% RSD or less for all validation experiments. The validated method was applied to a preclinical toxicology study in dogs after oral administration (200-1200 mg/kg) of the agent. Peak plasma resveratrol concentration (C(max)) for most animals was observed within 1-5 h of dosing, with group mean values in the 1.7-9.9 MUg/mL (7.5-43 MUM) range. Area under the plasma concentration-time curve (AUC) mean values for resveratrol ranged from 3.6 to 44 h MUg/mL for all study groups and were generally proportional to the dose, with no consistent statistically significant changes observed for gender or number of doses. Mean molecular-weight adjusted ratios of resveratrol metabolites to resveratrol for AUC ranged from 1 to 9 for resveratrol glucuronide and from 2 to 11 for resveratrol sulfate. PMID- 22079045 TI - Antioxidant activity-guided phytochemical investigation of Artemisia gmelinii Webb. ex Stechm.: isolation and spectroscopic challenges of 3,5-O-dicaffeoyl (epi?) quinic acid and its ethyl ester. AB - Although Artemisia gmelinii Webb. ex Stechm. has long been used in south and south-east Asia to treat many kinds of inflammatory diseases, up until now its bioactivity-coupled phytochemical characterization has not been reported. We identified one fraction of the methanolic extract of A. gmelinii as a hit in our antioxidant screening (DPPH) campaign. In order to identify the active radical scavenger components of the extract, a DPPH-HPLC spiking assay was carried out. Out of six detected known compounds caffeic acid and scopoletin had already been identified in the plant, but four of them, namely chlorogenic acid, 4-O caffeoylquinic acid, luteolin-7-O-glucoside, and apigenin-7-O-glucoside are first described here. Moreover, the two most active compounds of the mixture, 3,5-O dicaffeoylquinic acid (7) and its ethyl ester derivative (8) were isolated with preparative HPLC. The spectroscopic identification of 7 and 8 presented a surprising challenge due to literature ambiguities. These questions are discussed in detail. PMID- 22079046 TI - NMR analysis and site-specific protonation constants of streptomycin. AB - Streptomycin, the classical aminoglycoside antibiotic, generally considered the most basic drug compound was characterized in terms of protonation macro- and microconstants. 1H NMR-pH and 1H-13C HSQC-pH titrations were carried out on streptomycin and streptidine, a symmetrical constituent compound of reduced complexity to monitor the proton-binding processes of the basic sites. Accurate, undistorted, electrodeless pH measurement was ensured by a new set of in tube indicators. The microscopic protonation constants of the two guanidino groups of streptomycin were calculated by evaluating the various NMR-pH data and transferring the pair-interactivity parameter from streptidine to streptomycin. Inherent guanidino basicities fall in the range of 13.03-13.39 log k units, which drop to 12.48-12.85 upon protonation of the other site. pH-dependent distribution of the major microspecies and charge-related biological consequences are provided. PMID- 22079047 TI - Quantification of cabazitaxel in human plasma by liquid chromatography/triple quadrupole mass spectrometry: a practical solution for non-specific binding. AB - A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of cabazitaxel, a novel tubulin-binding taxane, in 100 MUl aliquots of human lithium heparinized plasma with deuterated cabazitaxel as internal standard. The sample extraction and cleaning-up involved a simple liquid-liquid extraction with 20 MUl aliquots of 4% ammonium hydroxide, 100 MUl aliquots of acetonitrile and 1 ml aliquots of n-butylchloride. Chromatographic separations were achieved on a reversed phase C18 column eluted at a flow-rate of 0.20 ml/min on a gradient of acetonitrile. The overall cycle time of the method was 5 min, with cabazitaxel eluting at 3.0 min. The multiple reaction monitoring transitions were set at 836>555 (m/z), and 842>561 (m/z) for cabazitaxel and the internal standard, respectively. The calibration curves were linear over the range of 1.00-100 ng/ml with the lower limit of quantitation validated at 1.00 ng/ml. The within-run and between-run precisions, also at the level of the LLQ, were within 8.75%, while the accuracy ranged from 88.5 to 94.1%. As dilution of samples prior to extraction resulted in a loss of cabazitaxel of approximately 6.5% per dilution step, a second calibration curve ranging from 40.0 to 4000 ng/ml was validated and was also linear. The within-run and between-run precisions in this range were within 4.99%, while the accuracy ranged from 95.8 to 100.3%. The method was successfully applied to samples derived from a clinical study. PMID- 22079048 TI - Prediction of short linear protein binding regions. AB - Short linear motifs in proteins (typically 3-12 residues in length) play key roles in protein-protein interactions by frequently binding specifically to peptide binding domains within interacting proteins. Their tendency to be found in disordered segments of proteins has meant that they have often been overlooked. Here we present SLiMPred (short linear motif predictor), the first general de novo method designed to computationally predict such regions in protein primary sequences independent of experimentally defined homologs and interactors. The method applies machine learning techniques to predict new motifs based on annotated instances from the Eukaryotic Linear Motif database, as well as structural, biophysical, and biochemical features derived from the protein primary sequence. We have integrated these data sources and benchmarked the predictive accuracy of the method, and found that it performs equivalently to a predictor of protein binding regions in disordered regions, in addition to having predictive power for other classes of motif sites such as polyproline II helix motifs and short linear motifs lying in ordered regions. It will be useful in predicting peptides involved in potential protein associations and will aid in the functional characterization of proteins, especially of proteins lacking experimental information on structures and interactions. We conclude that, despite the diversity of motif sequences and structures, SLiMPred is a valuable tool for prioritizing potential interaction motifs in proteins. PMID- 22079049 TI - The structure of the extracellular domain of the jumping translocation breakpoint protein reveals a variation of the midkine fold. AB - Jumping Translocation Breakpoint (JTB) is an orphan receptor that is conserved from nematodes to humans and whose gene expression in humans is strikingly upregulated in diverse types of cancers. Translocations occur frequently at the hJTB genomic locus, leading to multiple copies of a truncated JTB gene, which potentially encodes a soluble secreted ectodomain. In addition, JTB and its orthologs likely represent a unique and ancient protein family since homologs could not be identified by direct sequence comparison. In the present study, we have determined the NMR solution structure of the N-terminal ectodomain of human JTB, showing that its fold architecture is a new variant of a three-beta-strand antiparallel beta-meander. The JTB structure has a distant relationship to the midkine/pleiotrophin fold, particularly in the conservation of distinctive disulfide bridge patterns. The structure of this newly characterized small cysteine-rich domain suggests potential involvement of JTB in interactions with proteins or extracellular matrix and may help to uncover the elusive biological functions of this protein. PMID- 22079050 TI - Different binding modes of free and carrier-protein-coupled nicotine in a human monoclonal antibody. AB - Nicotine is the principal addictive component of tobacco. Blocking its passage from the lung to the brain with nicotine-specific antibodies is a promising approach for the treatment of smoking addiction. We have determined the crystal structure of nicotine bound to the Fab fragment of a fully human monoclonal antibody (mAb) at 1.85 A resolution. Nicotine is almost completely (>99%) buried in the interface between the variable domains of heavy and light chains. The high affinity of the mAb is the result of a charge-charge interaction, a hydrogen bond, and several hydrophobic contacts. Additionally, similarly to nicotinic acetylcholine receptors in the brain, two cation-pi interactions are present between the pyrrolidine charge and nearby aromatic side chains. The selectivity of the mAb for nicotine versus cotinine, which is the major metabolite of nicotine and differs in only one oxygen atom, is caused by steric constraints in the binding site. The mAb was isolated from B cells of an individual immunized with a nicotine-carrier protein conjugate vaccine. Surprisingly, the nicotine was bound to the Fab fragment in an orientation that was not compatible with binding to the nicotine-carrier protein conjugate. The structure of the Fab fragment in complex with the nicotine-linker derivative that was used for the production of the conjugate vaccine revealed a similar position of the pyridine ring of the nicotine moiety, but the pyrrolidine ring was rotated by about 180 degrees . This allowed the linker part to reach to the Fab surface while high-affinity interactions with the nicotine moiety were maintained. PMID- 22079051 TI - Toxicity and cosmesis outcomes after single fraction partial breast irradiation in early stage breast cancer. AB - BACKGROUND: To report the clinical outcome after a Single Shot 3D-CRT PBI (SSPBI) in breast cancer patients after conservative surgery (ClinicalTrials.gov Identifier: NCT01316328). METHODS: A dose of 18 Gy (in the first 4 patients) and 21 Gy (in the remaining 60 patients) was prescribed in a single session and delivered to the index area (i.e. the area of breast including the primary tumor bed and the surrounding tissue) using 3D-CRT with patients in prone position. Acute and late toxicity was assessed using the National Cancer Institute's CTC for Adverse Events. Cosmesis was defined based on modified Harvard criteria. Differences between dosimetric or clinical parameters of patients with/without G2 or more late toxicity or unsatisfactory (poor or fair) cosmetic outcome were evaluated with the Mann-Whitney test. Odds ratios and 95% confidence interval were calculated for cosmesis and fibrosis. Univariate and multivariate analyses(UVA/MVA) were used to determine covariates associated with an increase in fibrosis or fat necrosis rate. RESULTS: Sixty four patients were enrolled. With a median follow-up of 3 years, G2 and G3 subcutaneous fibrosis was detected in 20(31%) and in 8(13%) patients, and >=G2 fat necrosis was observed in 2(3%) patients. Good to excellent, fair and poor cosmesis was observed in 38(59%), 23(36%) and 3(5%) patients, respectively. Based on UVA, the breast volume receiving more than 21 Gy (V21 Gy) was found to be a predictor of the >=G1 or >=G2 fibrosis/fat necrosis. Based on MVA, V21 Gy was confirmed as a predictor for >=G1 fibrosis/fat necrosis, the results correlated as a trend for >=G2. Cosmesis was correlated with whole breast (WB) mean dose (p=0.030). CONCLUSION: Our choice of a single dose of 21 Gy significantly increased the treatment related toxicity. However, this should not discourage novel SSPBI approaches with lower equivalent doses. PMID- 22079052 TI - Intraoral myofascial therapy for chronic myogenous temporomandibular disorder: a randomized controlled trial. AB - OBJECTIVE: Studies investigating the efficacy of intraoral myofascial therapies (IMTs) for chronic temporomandibular disorder (TMD) are rare. The present study was an expansion of a previously published pilot study that investigated whether chiropractic IMT and the addition of education and self-care were superior to no treatment or IMT alone for 5 outcome measures-interincisal opening range, jaw pain at rest, jaw pain upon opening, jaw pain upon clenching, and global reporting of change-over the course of 1 year. METHODS: Ninety-three participants with myogenous TMD between the ages of 18 and 50 years experiencing chronic jaw pain of longer than 3 months in duration were recruited for the study. Successful applicants were randomized into 1 of 3 groups: (1) IMT consisting of 2 treatment interventions per week for 5 weeks, (2) IMT plus education and "self-care" exercises (IMTESC), and (3) wait-list control. The main outcome measures were used. Range of motion findings were measured by vernier callipers in millimeters, and pain scores were quantified using an 11-point self-reported graded chronic pain scale. Global reporting of change was a 7-point self-reported scale, balanced positively and negatively around a zero midpoint. RESULTS: There were statistically significant differences in resting, opening and clenching pain, opening scores, and global reporting of change (P < .05) in both treatment groups compared with the controls at 6 months and 1 year. There were also significant differences between the 2 treatment groups at 1 year. CONCLUSIONS: The study suggests that both chiropractic IMT and IMTESC were superior to no-treatment of chronic myogenous TMD over the course of 1 year, with IMTESC also being superior to IMT at 1 year. PMID- 22079053 TI - Effect of cervical spine manipulative therapy on judo athletes' grip strength. AB - OBJECTIVE: The objective of this study was to perform an investigation evaluating if cervical spinal manipulative therapy (SMT) can increase grip strength on judo athletes in a top 10 national-ranked team. METHODS: A single-blinded, prospective, comparative, pilot, randomized, clinical trial was performed with 18 athletes of both sexes from a judo team currently competing on a national level. The athletes were randomly assigned to 2 groups: chiropractic SMT and sham. Three interventions were performed on each of the athletes at different time points. Force measurements were obtained by a hydraulic dynamometer immediately before and after each intervention at the same period before training up to 3 weeks with at least 36 hours between interventions. RESULTS: Analysis of grip strength data revealed a statistically significant increase in strength within the treatment group after the first intervention (6.95% right, 12.61% left) as compared with the second (11.53% right, 17.02% left) and the third interventions (10.53% right, 16.81% left). No statistically significant differences were found in grip strength comparison within the sham group. Overall differences in strength were consistently significant between the study groups (P = .0025). CONCLUSION: The present study suggests that the grip strength of national level judo athletes receiving chiropractic SMT improved compared to those receiving sham. PMID- 22079054 TI - Perinatal morbidity and risk of hypoxic-ischemic encephalopathy associated with intrapartum sentinel events. AB - OBJECTIVE: To examine perinatal morbidity and rate of hypoxic-ischemic encephalopathy in infants exposed to intrapartum sentinel events. STUDY DESIGN: Retrospective cohort study from 2000-2005. Perinatal mortality, perinatal morbidity and rate of hypoxic-ischemic encephalopathy were compared in 3 groups of infants exposed to different risk factors for perinatal asphyxia (sentinel events, nonreassuring fetal status, elective cesarean section). RESULTS: Five hundred eighty-six infants were studied. Perinatal mortality was 6% in the sentinel event group and 0.3% in the nonreassuring fetal status group (relative risk, 2.4; 95% confidence interval, 1.95-2.94). Perinatal morbidity was 2-6 times more frequent in infants exposed to sentinel events; the incidence of hypoxic ischemic encephalopathy was 10%, compared with 2.5% in the nonreassuring fetal status group (relative risk, 1.93; 95% confidence interval, 1.49-2.52). No infant in the elective cesarean section group died, had perinatal morbidity, or developed encephalopathy. CONCLUSION: Intrapartum sentinel events are associated with a high incidence of perinatal morbidity and hypoxic-ischemic encephalopathy. PMID- 22079055 TI - Using light to see and control membrane traffic. AB - Cellular compartmentalization into discrete organelles is maintained by membrane trafficking including vesiculation and tubulation. Recent advances in superresolution imaging have begun to bring these small and dynamic events into focus. Most nanoscopes exploit, and are limited by, switching dyes ON and OFF. Using ground state depletion to switch dyes into long-lived dark states can exploit specific photophysical properties of dyes, such as redox potential or pK(a), and expand the repertoire of nanoscopy probes for multicolor imaging. Seeing is not enough, and new technologies based on homodimerization, heterodimerization and selective release can manipulate membrane trafficking in pulse-chase and light-controlled ways. Herein we highlight the utility and promise of these strategies and discuss their current limitations. PMID- 22079056 TI - Non-coding RNAs in cancer initiation and progression and as novel biomarkers. AB - Cancer represents a complex group of heterogeneous diseases. While many cancers share fundamental biological processes (hallmarks of cancer) necessary for their development and progression, cancers also distinguish themselves by their dependence on distinct oncogenic pathways. Over the last decade, targeted therapies have been introduced to the clinic with variable success. In truth, single targeted therapies may be successful in only a subset of malignancies but insufficient to address malignancies that often rely on multiple pathways, thus evading single targeted agents. Investigators have recently identified potentially functional components of the human genome that were previously thought to have no biological function. This discovery has added to the already established complexity of gene regulation in the pathogenesis of cancer. Non coding RNAs represent key regulators of gene expression. Improved knowledge of their biogenesis and function may in turn lead to a better understanding of the heterogeneity of malignancies and eventually be leveraged as diagnostic, prognostic and therapeutic targets. MicroRNAs (miRNAs or miRs) for example, have the capacity for the regulation of multiple genes and thus redirection or reprogramming of biological pathways. However, several other members of the non coding RNA family may be of equal biological relevance. In this review, we provide a perspective on emerging concepts in the clinical application of miRNA and other non-coding RNAs as biomarkers in cancer with an eye on the eventual integration of both miRNA and other non-coding RNA biology into our understanding of cancer pathogenesis and treatment. PMID- 22079058 TI - C1824T mutation in the LMNA gene has no association with senile cataract. AB - Mutations in the LMNA gene encoding lamins A/C are responsible for Hutchinson Gilford syndrome (HGS), a disorder of premature aging. Cataract is 1 of the main manifestations. The most prevalent mutation in Hutchinson-Gilford syndrome is C1824T, which activates a cryptic splice donor site to produce an abnormal lamin A protein. The purpose of this study was to investigate a possible association of the C1824T mutation with age-related cataract. Anterior lens capsule material was collected during cataract extraction surgery from 178 patients with senile cataract during 2007-2008. DNA and mRNA were extracted and sequenced for the LMNA gene. DNA and cDNA were screened for the C1824T mutation, which was not detected. Messenger RNA (mRNA) expression was normal, with no truncation. We found that human age-related nuclear cataract is not associated with LMNA gene mutations or truncation of lamin A. PMID- 22079057 TI - The 5-HT(2A) receptor and serotonin transporter in Asperger's disorder: A PET study with [11C]MDL 100907 and [11C]DASB. AB - Evidence from biochemical, imaging, and treatment studies suggest abnormalities of the serotonin system in autism spectrum disorders, in particular in frontolimbic areas of the brain. We used the radiotracers [(11)C]MDL 100907 and [(11)C]DASB to characterize the 5-HT(2A) receptor and serotonin transporter in Asperger's Disorder. Seventeen individuals with Asperger's Disorder (age=34.3 +/- 11.1 years) and 17 healthy controls (age=33.0 +/- 9.6 years) were scanned with [(11)C]MDL 100907. Of the 17 patients, eight (age=29.7 +/- 7.0 years) were also scanned with [11C]DASB, as were eight healthy controls (age=28.7 +/- 7.0 years). Patients with Asperger's Disorder and healthy control subjects were matched for age, gender, and ethnicity, and all had normal intelligence. Metabolite-corrected arterial plasma inputs were collected and data analyzed by two-tissue compartment modeling. The primary outcome measure was regional binding potential BP(ND). Neither regional [11C]MDL 100907 BP(ND) nor [11C]DASB BP(ND) was statistically different between the Asperger's and healthy subjects. This study failed to find significant alterations in binding parameters of 5-HT(2A) receptors and serotonin transporters in adult subjects with Asperger's disorder. PMID- 22079059 TI - Do image modality and registration method influence the accuracy of craniofacial navigation? AB - PURPOSE: Cone-beam computed tomography (CBCT) is increasingly used in craniofacial imaging and may be an interesting option for navigated surgery. The purpose of this study was to evaluate the accuracy of various registration techniques in CBCT compared with intraoperative and diagnostic multislice spiral computed tomography (MSCT). MATERIALS AND METHODS: High-resolution images of an anthropomorphic skull phantom with target markers were obtained using 2 CBCT machines (KaVo 3D eXam, ILUMA), an intraoperative MSCT (Sensation Open), and the standard diagnostic MSCT (LightSpeed VCT). Bone markers, a registration template, and an external registration frame were used for registration with an optical based navigation system. Target registration errors (TREs) were evaluated and statistically analyzed in SPSS (P < .05). RESULTS: The mean +/- standard deviation for overall TREs of the KaVo 3D eXam, ILUMA, Sensation Open, and LightSpeed VCT devices were 1.37 +/- 0.54, 1.67 +/- 0.65, 1.27 +/- 0.52, and 1.31 +/- 0.30 mm, respectively. The KaVo 3D eXam showed no significant differences compared with the MSCTs. The ILUMA imaged the external registration frame only marginally and showed significant higher TREs compared with the other registration methods (P < .001). In the 2 MSCTs, no significant differences between the registration methods were found. CONCLUSIONS: CBCT and intraoperative MSCT may show comparable TREs as standard diagnostic MSCT. Bone markers are the gold standard. Registration templates and external registration frames are valuable alternatives. When using only external registration frames, CBCTs with a large scan field are recommended. PMID- 22079060 TI - Concomitant removal of mandibular third molars during sagittal split osteotomy minimizes neurosensory dysfunction. AB - PURPOSE: Inferior alveolar nerve (IAN) injury is 1 of the most important postoperative complications after sagittal split osteotomy (SSO). The purpose of our study was to investigate the effects of the presence or absence of a mandibular third molar on the neurosensory recovery of the IAN after SSO. MATERIALS AND METHODS: A prospective cohort study enrolled a sample composed of patients who underwent SSO to correct mandibular deformities. The primary predictor variable was the status of the mandibular third molar at the time of SSO and it was divided into two levels, present at the time of SSO (Group I) or absent at the time of SSO (Group II). The primary outcome variable was neurosensory recovery of the IAN, assessed using the Medical Research Council scale, functional sensory recovery, and subjective evaluation. Neurosensory status was measured 3 times (preoperatively and 3 and 6 months postoperatively). Appropriate bivariate and multivariate statistics were computed, and the level of statistical significance was set at P < .05. RESULTS: A total of 120 SSOs were performed in 60 patients. Group I included 64 SSOs (mean patient age +/- SD 19.3 +/- 8.0 years) and group II, 56 SSOs (mean patient age 24.9 +/- 10.0 years). The Medical Research Council scale scores showed that the presence of third molars during SSO was associated with a statistically significant decreased incidence of neurosensory disturbance of the IAN at 3 and 6 months postoperatively (all P < .01). Functional sensory recovery was achieved more frequently in group I, but this difference remained significant only at 3 months after adjusting (P = .01). A "normal sensation" was subjectively reported more frequently in group I at 3 and 6 months postoperatively (P <= .05). CONCLUSIONS: The presence of third molars during SSO minimizes postoperative neurosensory disturbance of the IAN. PMID- 22079061 TI - An evaluation of face-bow transfer for the planning of orthognathic surgery. AB - PURPOSE: The purpose of this study was to evaluate the error magnitude in the clinical application of face-bow devices. Technical and methodologic inaccuracies, as well as deviations from reference planes, were determined. MATERIALS AND METHODS: The presented method is part of a 3-dimensional virtual planning procedure for orthognathic surgery and included 15 patients with dentoskeletal deformities. Cone beam computed tomography datasets obtained from patients with a referenced face-bow plane and a centric registration splint were matched with cone beam computed tomography datasets of the registered plaster model of the maxilla mounted in an articulator. To assess potential sources of methodologic errors, angulations were measured between the virtual face-bow plane and the horizontal cross bar of the virtual articulator. To evaluate the reproducibility of the anatomic reference plane, angulations between the Frankfort plane and the horizontal cross bar of the articulator were measured. Statistical significance was set at P < .05 and tested by univariate analysis of variance. RESULTS: Technical and methodologic errors showed a mean deviation of 3.5 degrees , with a median of 3.6 degrees and SD of 2.7 degrees . The values did not reach statistical significance (P = .1). However, there was a significant error (P < .05) in determining the position of the anatomic reference plane by face-bow transfer. The mean deviation was 7.7 degrees (values ranged between 1.2 degrees and 18.9 degrees ), with a median of 6.7 degrees and SD of 5.3 degrees . CONCLUSIONS: In this study the traditional use of face-bow devices showed inaccuracies in model mounting as well as in assignment of anatomic reference planes. Three-dimensional virtual computer-assisted planning seems to be more accurate than conventional methods. PMID- 22079062 TI - Free vascularized flaps for reconstruction of the mandible: complications, success, and dental rehabilitation. AB - PURPOSE: To evaluate complications and success of mandibular reconstruction with free fibula flaps, iliac crest flaps, and forearm flaps with reconstruction plates and to evaluate dental rehabilitation after these reconstructions. PATIENTS AND METHODS: Eighty-three patients with segmental mandibular defects were included. Correlation analyses were used to determine the relationship between reconstruction type and clinical parameters with recipient-site complications and success. The dental rehabilitation was evaluated in successfully reconstructed survivors. RESULTS: Multivariate analyses showed significant correlations between flap type and success (P < .0001). Of the patients, 51 (61%) were alive 2 years after the reconstruction. Mandibular reconstruction with a free forearm flap and reconstruction plate was associated with higher complication rates at the recipient site and higher failure rates compared with reconstruction with free vascularized bone flaps. Of the 32 successfully reconstructed survivors, 14 (44%) had a complete dental rehabilitation, of which 10 had dental implants and 4 did not. Only 6 (29%) of the edentulous survivors ultimately had an implant-supported prosthesis. CONCLUSIONS: Reconstruction of the mandible with a free vascularized bone flap is superior to reconstruction with a free forearm flap with a reconstruction plate. Complete dental rehabilitation was reached in fewer than half of the surviving patients. PMID- 22079063 TI - Can an arch bar replace a second lag screw in management of anterior mandibular fractures? AB - PURPOSE: To evaluate the efficacy of using a single lag screw combined with an arch bar in the management of anterior mandibular fractures and to compare this method with the traditional application of 2 lag screws. MATERIALS AND METHODS: We designed and implemented a randomized clinical trial and enrolled a sample of patients with anterior mandibular fractures. Twenty adult male patients were randomly divided into 2 equal groups according to the number of lag screws used for fracture fixation after securing the occlusion with intermaxillary fixation. In group A, the fractures were treated using 2 lag screws. In group B, the fractures were treated using a single lag screw and an arch bar on the teeth, spanning the fracture line. Clinical and radiographic evaluations were used to evaluate the efficacy of each fixation method immediately and at 2 and 4 months postoperatively. RESULTS: The clinical examination showed stable fixation with no mobility or infection in all cases. One patient in group A showed a slight occlusal discrepancy that was managed with occlusal adjustment. The pretraumatic occlusal relationship of all other patients was re-established. Postoperative radiographs showed properly reduced fracture segments with gradual bone healing. No significant difference was noted (P > .05) between the 2 groups in the development of postoperative complications. CONCLUSIONS: The use of 1 lag screw in conjunction with an arch bar across the fracture line is rigid and stable enough to manage anterior mandibular fractures without the need for supplemental intermaxillary fixation. The use of a single lag screw offers several advantages compared with the traditional use of 2 lag screws. These advantages include decreased cost, use of materials, healing time, and risk of associated morbidity. PMID- 22079064 TI - Three-dimensionally printed polycaprolactone and beta-tricalcium phosphate scaffolds for bone tissue engineering: an in vitro study. AB - PURPOSE: The purpose of this study was to evaluate porcine bone marrow-derived progenitor cell (pBMPC) proliferation and penetration into a novel 3 dimensionally printed scaffold. MATERIALS AND METHODS: Four different tissue engineering scaffolds to evaluate pBMPC proliferation and penetration were examined. Scaffolds were fabricated from polycaprolactone (PCL) or the combination of beta-tricalcium phosphate (beta-TCP) and PCL (50:50), with 2 separate channel sizes (1 mm [small (S)] vs 2 mm [large (L)]). Scaffolds were fabricated into 20 * 20 * 7-mm blocks by use of a TheriForm machine (Integra Life Sciences, Akron, OH). Four groups of scaffolds were examined for pBMPC proliferation and penetration: group 1, beta-TCP/PCL S; group 2, beta-TCP/PCL L; group 3, PCL S; and group 4, PCL L. Nonparametric mean (Kruskal-Wallis) and multiple comparisons tests were used to compare the 4 groups. RESULTS: No shrinkage or deformation was noted in any of the scaffold groups after 2 weeks of culture. Mean surface cell counts ranged from 13.4 to 87.8 cells/0.57 mm(2), with group 1 (beta-TCP/PCL S) having statistically significantly higher counts than the other groups (P < .001). Mean interior cell counts ranged from 10.9 to 75.6 cells/0.57 mm(2), with group 1 having the greatest interior cell count (P < .001). Total collagen formation ranged from 0.2% to 86%, with group 1 having the highest collagen formation (P < .001). CONCLUSIONS: The 3-dimensionally printed scaffold (beta-TCP/PCL) with 1-mm channels showed greater cellular proliferation, penetration, and collagen formation after a 2-week in vitro culture than the other scaffolds evaluated. beta-TCP/PCL S scaffolds warrant further evaluation for bone tissue engineering in vivo. PMID- 22079065 TI - Clinical significance of computed tomographic assessment and anatomic features of the inferior alveolar canal as risk factors for injury of the inferior alveolar nerve at third molar surgery. AB - PURPOSE: To assess the clinical features of the inferior alveolar canal (IAC) using computed tomography (CT) and to analyze the significance of CT examination at third molar surgery. MATERIALS AND METHODS: A retrospective cohort study was performed involving 99 patients (145 teeth). The relationship between cortication status, buccolingual position, and shape of the IAC on the CT image and inferior alveolar nerve (IAN) injury after third molar surgery were statistically analyzed. RESULTS: The shape of the IAC was categorized into 3 groups: round/oval, teardrop, and dumbbell. IAN injury was observed in 7 of 145 cases (4.8%). All 7 cases exhibited absence of cortication; 3 were dumbbell shape and 4 were round/oval. According to logistic regression analysis of cases with absence of cortication, IAC shape was closely related to IAN injury. CONCLUSIONS: These results suggest that assessment of the IAC shape and cortication status at third molar surgery may be clinically useful. PMID- 22079066 TI - How should the articular disk position be analyzed? AB - PURPOSE: To compare 2 methods used to determine the disk position based on sagittal magnetic resonance images. PATIENTS AND METHODS: A cross-sectional study of patients with the signs and symptoms of temporomandibular disorders was conducted. The patients' ages and gender distributions were collected. The disk position diagnosis from the clinical examination was considered the primary outcome. Three observers evaluated the presence of anterior displacement on magnetic resonance images according to 2 criteria: method 1 (12-o'clock position) and method 2 (location of the intermediate zone). To assess the intraobserver variability of the 2 methods, the examiners evaluated the same magnetic resonance images at the beginning of the study (time 1) and 40 days later (time 2). The intraobserver agreement was assessed using the observed agreement and the kappa statistic. McNemar's test was used to assess the differences between each method and the clinical examination findings (P < .05). The accuracy, sensitivity, specificity, and positive and negative predictive values were calculated by comparing the diagnosis from each method with that from the clinical examination (considered the reference standard). RESULTS: The final sample was composed of 20 subjects with a mean age of 33.0 +/- 33.7 years; 3 were men (15%) and 17 were women (85%). A statistically significant difference between the 2 methods was found. Method 1 yielded a greater percentage of anterior displaced disks (52.5%). The agreement between the clinical diagnosis and method 1 was lower (70.0%) than that between the clinical diagnosis and method 2 (87.5%). No statistically significant difference was found between the clinical diagnosis and method 2. CONCLUSION: The disk position should be judged according to the intermediate zone criterion. PMID- 22079067 TI - Streptococci-human papilloma virus interaction with ethanol exposure leads to keratinocyte damage. AB - PURPOSE: Ethanol, human papilloma virus (HPV), and poor oral hygiene are risk factors that have been attributed to oral carcinogenesis. Streptococci sp and HPV infections are common in the head and neck, often associated with sexual activity. Although HPV is linked to head and neck squamous cell carcinoma, it is unclear whether there is a similar role for Streptococci sp. This cell study examines whether Streptococci sp and HPV-16 with exposure to ethyl alcohol (ETOH) can act as cofactors in the malignant transformation of oral keratinocytes. MATERIALS AND METHODS: ETOH (0.1%-20% vol/vol) was used to investigate Streptococci sp attachment with immortalized E6-expressing HPV/HOK-16B cells, human oral buccal keratinocytes, and foreskin keratinocytes. Streptococci sp (Streptococci mutans [LT11]) and various strains of acetaldehyde (AA) producer and nonproducer Streptococcus salivarius (110-1, 109-2, 101-7, and 107-1) and a lactic acid producer bacterium, Lactobacillus rhamnosus (24-1 and 25-2), were examined for interactions with keratinocytes by use of a green dye (percent of cells with colonies after 24 hours). Carcinogens, AA, malondialdehyde, DNA damage, and proliferation (5'-bromo-2-deoxyuridine) among keratinocytes were also quantified. RESULTS: AA and malondialdehyde production from permissible Streptococci sp significantly increased with attachment to keratinocytes, whereas L rhamnosus did not significantly attach to keratinocytes. This attachment was associated with enhanced levels of AA adduct formation, proliferation (5'-bromo-2 deoxyuridine incorporation), and enhanced migration through integrin-coated basement membrane by HPV oral keratinocytes, which are characteristics of a malignant phenotype. CONCLUSIONS: These cell studies suggest that oral Streptococci sp and HPV (HPV-16) cooperate to transform oral keratinocytes after low-level ETOH (1%) exposure. These results appear to suggest a significant clinical interaction, but further validation is warranted. PMID- 22079068 TI - Comparison of current perception threshold electrical testing to clinical sensory testing for lingual nerve injuries. AB - PURPOSE: We performed a retrospective study of lingual nerve injury assessment comparing the techniques of current perception threshold testing versus clinical sensory testing. PATIENTS AND METHODS: We designed and implemented a cross sectional study and enrolled a patient sample with lingual nerve injuries presenting for treatment to the principal investigator. The predictor variables were clinical sensory testing modalities (ie, temperature, nocioception, vibration, 2-point discrimination, brush stroke, and von Frey monofilament perception). The primary outcome variable was the electrical current perception thresholds of the tongue dorsum (neurometer measurements at 5, 250, and 2,000 Hz). Comparisons were established with the ipsilateral affected and contralateral unaffected lingual nerve distributions. The associations between the clinical sensory testing and current perception threshold measurements were assessed using correlation coefficients, with the level of statistical significance set at P < .05. RESULTS: A total of 40 patients (13 males and 27 females) were included in the present study. The average age of these patients was 34 years (range 13 to 66). Significant correlations were observed between the electrical stimulation thresholds at 2,000 Hz and the 2-point discrimination, reaction to brushing, reaction to vibration, and von Frey fiber thresholds, between the electrical stimulation thresholds at 250 Hz to the nociceptive and thermal thresholds, and between the electrical stimulation thresholds at 5 Hz to thermal stimuli. CONCLUSIONS: The significant correlations observed in the present study indicate that current perception threshold can be a complementary or alternative tool in the assessment and evaluation of lingual nerve injuries. PMID- 22079069 TI - Human immunodeficiency virus-associated Burkitt's lymphoma in oral cavity of Japanese patient. PMID- 22079070 TI - Sialadenoma papilliferum of the hard palate: a case report. PMID- 22079071 TI - Yolk-sac tumor of the postauricular region: case report and review of the literature. PMID- 22079072 TI - Responses of dopaminergic, serotonergic and noradrenergic networks to acute levo tetrahydropalmatine administration in naive rats detected at 9.4 T. AB - AIM: The aim of this study was to understand the neuropharmacological characteristics of levo-tetrahydropalmatine (l-THP), a recently found potential treatment for drug addiction, and discover its neural correlates and sites of action. METHODS: High-field pharmacological magnetic resonance imaging (phMRI) was used to detect activation induced by acute l-THP administration in the naive rat brain at dose levels of 5, 10, 20 and 40 mg/kg. RESULTS: Interestingly, the pharmacological profile of l-THP selectively binds to the receptors of the dopaminergic, serotonergic and noradrenergic systems. Using the phMRI method, it was demonstrated that l-THP selectively activated the key brain regions of the dopaminergic, serotonergic and noradrenergic systems in a dose-dependent manner. CONCLUSION: Numerous studies suggest a critical role of monoamines in the behavioral, pharmacological and addictive properties of psychostimulants. It is suggested that l-THP holds great potential to be a therapeutic medication for drug addiction. PMID- 22079073 TI - Subject-specific changes in brain white matter on diffusion tensor imaging after sports-related concussion. AB - BACKGROUND AND PURPOSE: Current approaches to diffusion tensor imaging (DTI) analysis do not permit identification of individual-level changes in DTI indices. We investigated the ability of wild bootstrapping analysis to detect subject specific changes in brain white matter (WM) before and after sports-related concussion. MATERIALS AND METHODS: A prospective cohort study was performed in nine high school athletes engaged in hockey or football and six controls. Subjects underwent DTI pre- and postseason within a 3-month interval. One athlete was diagnosed with concussion (scanned within 72 h), and eight suffered between 26 and 399 subconcussive head blows. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in each WM voxel. Bootstrap samples were generated, and a permuted t test was used to compare voxel-wise FA/MD changes in each subject pre- vs. postseason. RESULTS: The percentage of WM voxels with significant (p<.05) pre-post FA changes was highest for the concussion subject (3.2%), intermediary for those with subconcussive head blows (mean 1.05%+/-.15%) and lowest for controls (mean 0.28%+/-.01%). Similarly, the percentage of WM voxels with significant MD changes was highest for the concussion subject (3.44%), intermediary for those with subconcussive head blows (mean 1.48%+/-.17%) and lowest for controls (mean 0.48%+/-.05%). Significantly changed FA and MD voxels colocalized in the concussion subject to the right corona radiata and right inferior longitudinal fasciculus. CONCLUSIONS: Wild bootstrap analysis detected significantly changed WM in a single concussed athlete. Athletes with multiple subconcussive head blows had significant changes in a percentage of their WM that was over three times higher than controls. Efforts to understand the significance of these WM changes and their relationship to head impact forces appear warranted. PMID- 22079074 TI - International collaborative proficiency study of Human Papillomavirus type 16 serology. AB - We performed an international proficiency study of Human Papillomavirus (HPV) type 16 serology. A common methodology for serology based on virus-like particle (VLP) ELISA was used by 10 laboratories in 6 continents. The laboratories used the same VLP reference reagent, which was selected as the most stable, sensitive and specific VLP preparation out of VLPs donated from 5 different sources. A blinded proficiency panel consisting of 52 serum samples from women with PCR verified HPV 16-infection, 11 control serum samples from virginal women and the WHO HPV 16 International Standard (IS) serum were distributed. The mean plus 3 standard deviations of the negative control serum samples was the most generally useful "cut-off" criterion for distinguishing positive and negative samples. Using sensitivity of at least 50% and a specificity of 100% as proficiency criteria, 6/10 laboratories were proficient. In conclusion, an international Standard Operating Procedure for HPV serology, an international reporting system in International Units (IU) and a common "cut-off" criterion have been evaluated in an international HPV serology proficiency study. PMID- 22079075 TI - Diverse microbial exposure - consequences for vaccine development. AB - Numerous epidemiological studies suggest that there is an inverse relationship between "immunologically mediated diseases of affluence", such as allergy, diabetes and inflammatory bowel disease on one hand and few infections encountered in early childhood, on the other hand. Careful analysis of the epidemiological, clinical and animal studies taken together, however, suggests that the protection is mediated by broad exposure to a wealth of commensal, non pathogenic microorganisms early in life, rather than by infections. Microbial exposure has little relationship with "hygiene" in the usual meaning of the word and the term "hygiene hypothesis" is therefore misleading. A better term would be "microbial deprivation hypothesis". The suggestion that childhood infections would protect against allergic disease led to unfortunate speculations that vaccinations would increase the risk for allergies and diabetes. Numerous epidemiological studies have therefore been conducted, searching for a possible relationship between various childhood vaccinations on one hand and allergy on the other hand. It is reasonable from these studies to conclude that vaccinations against infectious agents neither significantly increase, nor reduce the likelihood of immunologically mediated diseases. It is established that the postnatal maturation of immune regulation is largely driven by exposure to microbes. Germ free animals manifest excessive immune responses when immunised and they do not develop normal immune regulatory function. The gut is by far the largest source of microbial exposure, as the human gut microbiome contains up to 1014 bacteria, i.e. ten times the number of cells in the human body. Several studies in recent years have shown differences in the composition of the gut microbiota between allergic and non-allergic individuals and between infants living in countries with a low and a high prevalence of immune mediated diseases. The administration of probiotic bacteria to pregnant mothers and postnatal to their infants has immune modulatory effects. So far, however, probiotic bacteria do not seem to significantly enhance immune responses to vaccines. The potential to improve vaccine responses by modifying the gut microbiota in infants and the possibility to employ probiotic bacteria as adjuvants and/or delivery vehicles, is currently explored in several laboratories. Although to date few clinical results have been reported, experimental studies have shown some encouraging results. PMID- 22079076 TI - Process optimization and scale-up for production of rabies vaccine live adenovirus vector (AdRG1.3). AB - Rabies virus is an important causative agent of disease resulting in an acute infection of the nervous system and death. Although curable if treated in a timely manner, rabies remains a serious public health issue in developing countries, and the indigenous threat of rabies continues in developed countries because of wildlife reservoirs. Control of rabies in wildlife is still an important challenge for governmental authorities. There are a number of rabies vaccines commercially available for control of wildlife rabies infection. However, the vaccines currently distributed to wildlife do not effectively immunize all at-risk species, particularly skunks. A replication competent recombinant adenovirus expressing rabies glycoprotein (AdRG1.3) has shown the most promising results in laboratory trials. The adenovirus vectored vaccine is manufactured using HEK 293 cells. This study describes the successful scale-up of AdRG1.3 adenovirus production from 1 to 500 L and the manufacturing of large quantities of bulk material required for field trials to demonstrate efficacy of this new candidate vaccine. The production process was streamlined by eliminating a medium replacement step prior to infection and the culture titer was increased by over 2 fold through optimization of cell culture medium. These improvements produced a more robust and cost-effective process that facilitates industrialization and commercialization. Over 17,000 L of AdRG1.3 adenovirus cultures were manufactured to support extensive field trials. AdRG1.3 adenovirus is formulated and packaged into baits by Artemis Technologies Inc. using proprietary technology. Field trials of AdRG1.3 rabies vaccine baits have been conducted in several Canadian provinces including Ontario, Quebec and New Brunswick. The results from field trials over the period 2006-2009 demonstrated superiority of the new vaccine over other licensed vaccines in immunizing wild animals that were previously difficult to vaccinate. PMID- 22079077 TI - Vaccination with BM86, subolesin and akirin protective antigens for the control of tick infestations in white tailed deer and red deer. AB - Red deer (Cervus elaphus) and white-tailed deer (Odocoileus virginianus) are hosts for different tick species and tick-borne pathogens and play a role in tick dispersal and maintenance in some regions. These factors stress the importance of controlling tick infestations in deer and several methods such as culling and acaricide treatment have been used. Tick vaccines are a cost-effective alternative for tick control that reduced cattle tick infestations and tick-borne pathogens prevalence while reducing the use of acaricides. Our hypothesis is that vaccination with vector protective antigens can be used for the control of tick infestations in deer. Herein, three experiments were conducted to characterize (1) the antibody response in red deer immunized with recombinant BM86, the antigen included in commercial tick vaccines, (2) the antibody response and control of cattle tick infestations in white-tailed deer immunized with recombinant BM86 or tick subolesin (SUB) and experimentally infested with Rhipicephalus (Boophilus) microplus, and (3) the antibody response and control of Hyalomma spp. and Rhipicephalus spp. field tick infestations in red deer immunized with mosquito akirin (AKR), the SUB ortholog and candidate protective antigen against different tick species and other ectoparasites. The results showed that deer produced an antibody response that correlated with the reduction in tick infestations and was similar to other hosts vaccinated previously with these antigens. The overall vaccine efficacy was similar between BM86 (E=76%) and SUB (E=83%) for the control of R. microplus infestations in white-tailed deer. The field trial in red deer showed a 25-33% (18-40% when only infested deer were considered) reduction in tick infestations, 14-20 weeks after the first immunization. These results demonstrated that vaccination with vector protective antigens could be used as an alternative method for the control of tick infestations in deer to reduce tick populations and dispersal in regions where deer are relevant hosts for these ectoparasites. PMID- 22079078 TI - An adjunctive therapeutic vaccine against reactivation and post-treatment relapse tuberculosis. AB - Preventing latently infected or inadequately treated individuals from progressing to active disease could make a major impact on tuberculosis (TB) control worldwide. The purpose of this study was to evaluate a new approach to prevent reactivation and TB relapse that combines drug treatment and vaccination. Mycobacterium tuberculosis harbors a gene called mce1R that, in vivo, negatively regulates a 13-gene cluster called the mce1 operon. In a Cornell mouse model, BALB/c mice infected with M. tuberculosis H37Rv disrupted in mce1R consistently develop latent infection and reactivation disease. We used this new mouse model to test a recombinant M. tuberculosis cell wall protein (Mce1A), encoded by a gene in the mce1 operon, for its ability to prevent post-treatment TB. At 32 weeks of follow-up, a complete sterilizing protection was observed in lungs of the vaccinated mice. Mce1A but not phosphate-buffered saline administered intraperitoneally during the period of latent infection prevented disease progression and proliferation of M. tuberculosis mce1R mutant. The only visible lung lesions in vaccinated mice included small clusters of lymphocytes, while the unvaccinated mice showed progressively enlarging granulomas comprised of foamy macrophages surrounded by lymphocytes. The combination of anti-TB drugs and a vaccine may serve as a powerful treatment modality against TB reactivation and relapse. PMID- 22079079 TI - Safety and immunogenicity of a novel nanoemulsion mucosal adjuvant W805EC combined with approved seasonal influenza antigens. AB - BACKGROUND: Improving the systemic and mucosal immune response following intranasal vaccination could enhance disease protection against respiratory pathogens. We assessed the safety and immunogenicity of a novel nanoemulsion mucosal adjuvant W(80)5EC combined with approved seasonal influenza antigens. METHODS: This was a first-in-human Phase I study in 199 healthy adult volunteers randomized to receive a single intranasal administration of 5%, 10%, 15% or 20% W(80)5EC, combined with 4 or 10 MUg strain-specific Fluzone((r)) HA, compared with intranasal PBS, intranasal Fluzone((r)), or 15 ug strain-specific intramuscular Fluzone((r)). Safety was evaluated by physical examination, laboratory parameters, symptom diaries, and adverse event reports. Serum HAI titers and nasal wash IgA were assessed at baseline as well as 28 and 60 days after vaccination. RESULTS: W(80)5EC adjuvant combined with seasonal influenza antigens was well tolerated without safety concerns or significant adverse events. The highest dose of 20% W(80)5EC combined with 10 MUg strain-specific HA elicited clinically meaningful systemic immunity based on increases in serum HAI GMT and >= 70% seroprotection for all 3 influenza strains, as well as a rise in antigen-specific IgA in nasal wash specimens. CONCLUSIONS: W(80)5EC adjuvant was safe and well tolerated in healthy adult volunteers and elicited both systemic and mucosal immunity following a single intranasal vaccination. PMID- 22079080 TI - The non-toxic and biodegradable adjuvant Montanide ISA 720/CpG can replace Freund's in a cancer vaccine targeting ED-B--a prerequisite for clinical development. AB - We have recently shown that immunization against the extra domain-B (ED-B) of fibronectin, using Freund's adjuvant, reduces tumor growth in mice by 70%. In the present study we compare the immune response generated against ED-B using the non toxic and biodegradable adjuvant Montanide ISA 720/CpG with the response elicited by Freund's adjuvant. Montanide ISA 720/CpG induced anti-ED-B antibodies with higher avidity and less variable levels between individuals than Freund's. Moreover, the duration of the immune response was longer and the generation of anti-ED-B antibodies in naive mice was faster, when Montanide ISA 720/CpG was used. We conclude that it is possible to replace the mineral oil based adjuvant Freund's with an adjuvant acceptable for human use, which is a prerequisite for transfer of the ED-B vaccine to the clinic. PMID- 22079081 TI - The untold truth about "bath salt" highs: A case series demonstrating local tissue injury. AB - The epidemic of injecting cathinone derivatives, marketed as "bath salts", by intravenous drug users among inner city Dubliners led to an associated rise in soft tissue complications. The spectrum of the cases encountered, ranging from self-limiting cellulitis to extensive abscess formation, at a single institution is described. PMID- 22079082 TI - [Evaluation of the immunoblotting for the detection of immunoglobulin G Toxoplasma antibodies in immunocompetent patients]. AB - The serological tests commonly used for the diagnosis of toxoplasmosis raise the problem of the interpretation of the borderline immunoglobulin G (IgG) levels and discordant results between various tests. OBJECTIVE: The purpose of our study was to evaluate the contribution of the immunoblotting in the detection of specific IgG in acquired toxoplasmosis of immunocompetent patients especially when levels are equivocal or discordant in enzyme-linked immunosorbent assay (Elisa) and indirect fluorescent antigen test (IFAT). MATERIAL AND METHODS: [corrected] We tested three groups of sera. The first included 87 positive sera, the second 33 negative sera, and the last one 29 equivocal sera. RESULTS: Results obtained with the first and the second group of sera led us to identify the bands 30kDa and 32kDa as markers of the toxoplasmic infection. The simultaneous presence of both bands showed a sensitivity of 91.5%, a specificity of 96.9%, a VPP of 98.7%, a VPN of 74.4% and a Youden's index of 0.88. Our findings suggest that the presence of these two bands is a reliable criterion for the confirmation of the presence of anti-toxoplasmic IgG in the corresponding serum. The immunoblot allowed us to ascertain serological status of 27 (93.1%) patients from the third group in which results were discrepant or equivocal in Elisa and/or in IFAT. CONCLUSION: Immunoblot is a useful serological test for detection of very low or equivocal titers. PMID- 22079083 TI - Transgenic inactivation of murine myostatin does not decrease the severity of disease in a model of Spinal Muscular Atrophy. AB - Spinal Muscular Atrophy (SMA) is a devastating neurodegenerative disease and is a leading genetic cause of infantile death. SMA is caused by the homozygous loss of Survival Motor Neuron-1 (SMN1). The presence of a nearly identical copy gene called SMN2 has led to the development of several strategies that are designed to elevate SMN levels, and it is clear that SMN2 is an important modifier gene. However, the possibility exists that SMN-independent strategies to lessen the severity of the SMA phenotype could provide insight into disease development as well as aid in the identification of potential therapeutic targets. Muscle enhancement has been considered an interesting target for a variety of neurodegenerative diseases, including SMA. Previously we have shown in SMA mice that delivery of recombinant follistatin resulted in an extension in survival and a general lessening of disease severity. Follistatin is known to functionally block myostatin (MSTN), a potent inhibitor of muscle development. However, follistatin is a multifaceted protein involved in a variety of cellular pathways. To determine whether MSTN inhibition was the primary pathway associated with the previously reported follistatin results, we generated an animal model of SMA in which Mstn was genetically inactivated. In this report we characterize the novel SMA/Mstn model and demonstrate that Mstn inactivation does not significantly enhance muscle development in neonatal animals, nor does it result in an amelioration of the SMA phenotype. PMID- 22079084 TI - Potential legal protection problems in the use of compulsory commitment in mental health care in Norway. AB - Compulsory commitment in mental health care represents a dramatic infringement on an individual's life. In Norway, this deprivation of liberty is based on a professional medical assessment that does not require a court verdict. This article presents possible changes that may increase legal protection for the mentally ill. The concept of legal protection has at least two definitions: the state's protection of the individual's legal rights (including the right to health care) and the protection afforded to citizens from abuse and arbitrary actions by the state. Infringements on personal liberty without consent require such legal authority as is found in the Human Rights Conventions. These Conventions have precedence over national laws. Norwegian legislation is based on confidence in psychiatry as a profession. This confidence allows professionals to treat patients against their will. In some countries, initial court action is necessary before compulsory mental health care can be implemented. This should also be possible in Norway in most cases, with the exception of life-threatening situations. PMID- 22079085 TI - The "untreatability" of psychopathy and hospital commitment in the USA. AB - One argument in support of a public policy of not subjecting persons with psychopathic disorders to civil or criminal commitment is that these disorders do not improve with treatment. This article examines the relationship between the assumption of untreatability of psychopathic disorders and outpatient civil commitment, inpatient civil commitment, and insanity acquittee commitment. Research on the treatability of psychopathy is reviewed and the treatment of conditions co-morbid with psychopathy is considered. Research evidence is insufficient to support the conclusion that psychopathy is improved, worsened or not affected by treatment. Evidence does support effective treatments for conditions that can be co-morbid with psychopathic disorders including impulsive aggression which can be interpreted as a manifestation of psychopathic disorder. The absence of evidence based treatment efficacy for psychopathic disorders is a logical reason for not subjecting individuals with only a psychopathic disorder to involuntary hospitalization. This assumption should not becloud the possibility of treatable co-morbid conditions which may or may not qualify for involuntary hospitalization. Where the primary mental disorder, for which an individual is involuntarily hospitalized, results in behavioral improvement, the continued presence of a psychopathic disorder itself, should not be sufficient reason to continue coerced confinement. Even so, where the primary disorder is incompletely treated, psychopathy can be considered a risk factor when deciding upon the appropriate time for discharge and when formulating a safe and effective after care plan. PMID- 22079086 TI - The right of caregivers to access health information of relatives with mental illness. AB - This article reviews the legal, ethical and practical challenges of complying with the Ontario Personal Health Information Protection Act (PHIPA) within the context of a Canadian mental health system that is overburdened and under resourced. The advent of deinstitutionalization has placed significantly increased responsibilities on the families of mentally ill individuals. While research evidences that involving family members in the care of their mentally ill relatives improves treatment outcomes, mental health practitioners constantly face the challenge of engaging family caregivers while also complying with privacy laws. The authors propose an Ontario Caregiver Recognition Act (OCRA) to formally recognize family caregivers as informal health information custodians based on the practice of other jurisdictions which incorporate the rights of family members actively engaged in providing care to their mentally ill relatives. PMID- 22079087 TI - Methodological issues in monitoring the use of coercive measures. AB - PURPOSE: In many European countries, initiatives have emerged to reduce the use of seclusion and restraint in psychiatric institutions. To study the effects of these initiatives at a national and international level, consensus on definitions of coercive measures, assessment methods and calculation procedures of these coercive measures are required. The aim of this article is to identify problems in defining and recording coercive measures. The study contributes to the development of consistent comparable measurements definitions and provides recommendations for meaningful data-analyses illustrating the relevance of the proposed framework. METHODS: Relevant literature was reviewed to identify various definitions and calculation modalities used to measure coercive measures in psychiatric inpatient care. Figures on the coercive measures and epidemiological ratios were calculated in a standardized way. To illustrate how research in clinical practice on coercive measures can be conducted, data from a large multicenter study on seclusion patterns in the Netherlands were used. RESULTS: Twelve Dutch mental health institutes serving a population of 6.57 million inhabitants provided their comprehensive coercion measure data sets. In total 37 hospitals and 227 wards containing 6812 beds were included in the study. Overall seclusion and restraint data in a sample of 31,594 admissions in 20,934 patients were analyzed. Considerable variation in ward and patient characteristics was identified in this study. The chance to be exposed to seclusion per capita inhabitants of the institute's catchment areas varied between 0.31 and 1.6 per 100.000. Between mental health institutions, the duration in seclusion hours per 1000 inpatient hours varied from less than 1 up to 18h. The number of seclusion incidents per 1000 admissions varied between 79 up to 745. The mean duration of seclusion incidents of nearly 184h may be seen as high in an international perspective. CONCLUSION: Coercive measures can be reliably assessed in a standardized and comparable way under the condition of using clear joint definitions. Methodological consensus between researchers and mental health professionals on these definitions is necessary to allow comparisons of seclusion and restraint rates. The study contributes to the development of international standards on gathering coercion related data and the consistent calculation of relevant outcome parameters. PMID- 22079088 TI - Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension. AB - OBJECTIVE: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. METHODS: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. RESULTS: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. CONCLUSION: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated. PMID- 22079089 TI - Thrombolytic treatment of simultaneous pulmonary embolism and impending paradoxical embolism through a patent foramen ovale: a different thrombolytic regimen. AB - A 72 year-old woman was admitted with a one-week history of weakness, right limb pain and progressive breathlessness. Her blood pressure was 60/40 mmHg, ECG showed inverted T waves in the precordial leads and incomplete right bundle branch block (RBBB). Transthoracic echocardiography revealed a large serpentine mobile mass across the atrial septum and mitrale valve extending into the left ventricular cavity. The right ventricle was dilated and peak systolic tricuspid annular velocity (RV-Sm) was 6.5 cm/sn, indicate right ventricular systolic function was severely depressed. Transoesophageal echocardiography showed a large, mobile thrombus in the foramen ovale, extending into the left atrium and ventricle. As the patient was in a haemodynamically compromised condition, high dose rapid infusion of streptokinase was administered. However, the thrombus did not fully resolve with this intervention. Therefore, low dose continuous streptokinase infusion was administered for an additional 72 h resulting in full resolution of the lesion by the third day of therapy. The optimal management of impending paradoxical embolism remains unclear. Prolonged continuous thrombolytic infusion may be a option for patients who do not experience full resolution of high risk thrombi with conventional thrombolytic therapy. PMID- 22079090 TI - Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation. AB - The ligand-bound thyroid hormone receptor (TR) is known to repress via a negative TRE (nTRE) the expression of E2F1, a key transcription factor that controls the G1/S phase transition. Alien has been identified as a novel interacting factor of E2F1 and acts as a corepressor of E2F1. The detailed molecular mechanism by which Alien inhibits E2F1 gene expression remains unclear. Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, the E2F1 and the nTRE site of the E2F1 gene while the recruitment to the negative thyroid hormone response element (nTRE) is induced by the ligand-bound TRbeta1 within the E2F1 gene promoter. We show that, overexpression of ESET promotes, whereas knockdown of ESET releases, the inhibition of TRbeta1-regulated gene transcription upon T3 stimulation; and H3K9 methylation is required for TRbeta1-repressed transcription. Furthermore, depletion of ESET impairs thyroid hormone-repressed proliferation as well as the G1/S transition of the cell cycle. Taken together, our data indicate that ESET is involved in TRbeta1-mediated transcription repression and provide a molecular basis of thyroid hormone-induced repression of proliferation. PMID- 22079091 TI - Clathrin-mediated endocytic proteins are upregulated in the cortex of the Tg2576 mouse model of Alzheimer's disease-like amyloid pathology. AB - Amyloid-beta (Abeta) is cleaved from amyloid precursor protein (APP) predominantly after APP has trafficked through the secretory pathway and then become re-internalised by endocytosis. Clathrin-mediated and, more recently, clathrin-independent endocytosis have both been implicated in this process. Furthermore, endocytic abnormalities have been identified in cases of Alzheimer's disease (AD), however, the relevance of these changes to the aetiology of the disease remains unclear. We therefore examined the expression of proteins related to these endocytic processes in the cortex of Tg2576 mice that overexpress the Swedish mutation in APP, and consequently overexpress Abeta, to determine if there were any changes in their associated pathways. We identified significant increases in the levels of clathrin, dynamin and PICALM, all proteins intimately involved with the clathrin-mediated endocytic pathway, in the transgenic animals. However, levels of proteins associated with flotillin or caveolin-mediated endocytic pathways remained unchanged. These results emphasise the importance of clathrin-mediated endocytosis in the aetiology of AD and reinforce the results of the recent GWAS studies that identified genes for clathrin-mediated endocytosis as susceptibility genes for AD. Such studies in transgenic mice will allow us to learn more about the role of clathrin-mediated endocytosis in AD. PMID- 22079092 TI - Transmembrane myosin chitin synthase involved in mollusc shell formation produced in Dictyostelium is active. AB - Several mollusc shells contain chitin, which is formed by a transmembrane myosin motor enzyme. This protein could be involved in sensing mechanical and structural changes of the forming, mineralizing extracellular matrix. Here we report the heterologous expression of the transmembrane myosin chitin synthase Ar-CS1 of the bivalve mollusc Atrina rigida (2286 amino acid residues, M.W. 264 kDa/monomer) in Dictyostelium discoideum, a model organism for myosin motor proteins. Confocal laser scanning immunofluorescence microscopy (CLSM), chitin binding GFP detection of chitin on cells and released to the cell culture medium, and a radiochemical activity assay of membrane extracts revealed expression and enzymatic activity of the mollusc chitin synthase in transgenic slime mold cells. First high-resolution atomic force microscopy (AFM) images of Ar-CS1 transformed cellulose synthase deficient D. discoideumdcsA(-) cell lines are shown. PMID- 22079093 TI - Proteomic analysis of the 20S proteasome (PSMA3)-interacting proteins reveals a functional link between the proteasome and mRNA metabolism. AB - The 26S proteasome is a large multi-subunit protein complex that exerts specific degradation of proteins in the cell. The 26S proteasome consists of the 20S proteolytic particle and the 19S regulator. In order to be targeted for proteasomal degradation most of the proteins must undergo the post-translational modification of poly-ubiquitination. However, a number of proteins can also be degraded by the proteasome via a ubiquitin-independent pathway. Such degradation is exercised largely through the binding of substrate proteins to the PSMA3 (alpha 7) subunit of the 20S complex. However, a systematic analysis of proteins interacting with PSMA3 has not yet been carried out. In this report, we describe the identification of proteins associated with PSMA3 both in the cytoplasm and nucleus. A combination of two-dimensional gel electrophoresis (2D-GE) and tandem mass-spectrometry revealed a large number of PSMA3-bound proteins that are involved in various aspects of mRNA metabolism, including splicing. In vitro biochemical studies confirmed the interactions between PSMA3 and splicing factors. Moreover, we show that 20S proteasome is involved in the regulation of splicing in vitro of SMN2 (survival motor neuron 2) gene, whose product controls apoptosis of neurons. PMID- 22079094 TI - Topical timolol for the treatment of epistaxis in hereditary hemorrhagic telangiectasia. PMID- 22079095 TI - Comparative audiometric evaluation of hearing loss between the premenopausal and postmenopausal period in young women. AB - AIM: The aim of this study was to determine the audiologic status and severity of hearing loss in different frequencies between the premenopausal and postmenopausal period in women. MATERIALS AND METHODS: This prospective study involved 28 premenopausal and 27 postmenopausal women. Premenopausal and postmenopausal women were younger than 46 years. Age range for premenopausal and menopause patients was 37 to 46 years. The mean age of menopause women with sensorineural hearing loss in our study was not suitable for the age range of presbyacousis that is commonly seen. Each subject was tested with low- (250-2000 Hz) and high-frequency (4000-8000 Hz) audiometry. For each set of tests, mean values of air conduction at each frequency were calculated for the premenopausal and postmenopausal groups and compared. RESULTS: The mean ages of the women on premenopausal and postmenopausal groups were 42.0 +/- 2.4 and 43.4 +/- 2.6 years, respectively. Duration of menopausal period in second group was 2.03 +/- 0.85 years. The corresponding mean body mass indexes were 29.7 +/- 2.9 and 31.1 +/- 3.8 kg/m(2). There was no statistical significance between the 2 groups in mean ages and mean body mass indexes. Hearing thresholds at low and high frequencies were analyzed between the 2 groups in Table 2. At low (250, 500, 1000, and 2000 Hz) and high frequencies (4000, 6000, and 8000 Hz), the mean air-conduction threshold values between the 2 groups were not statistically significant. CONCLUSION: Estrogen deficiency may not elevate hearing thresholds in early postmenopausal period; however, further studies of larger series are needed to confirm this. PMID- 22079096 TI - A potential in silico antibody-antigen based diagnostic test for precise identification of Acinetobacter baumannii. AB - Acinetobacter baumannii is a problematic nosocomial pathogen. The resistance to a wide range of antimicrobial agents, attributable to its biofilm phenotype, makes the treatment very difficult. Biofilm is a common feature of most pathogens. Biofilm associated proteins (Bap) are cellular surface components directly involved in biofilm formation process. The dearth of a fast precise diagnostic test and versatility of Bap sequences in A. baumannii were intuitions to design this study. In silico analysis is a reliable alternative to laborious experimental work in this connection. Databases were searched for an antigenic conserved region of Bap specific to A. baumannii. The region was selected based on alignments and propensity scales. Tertiary structure for this region was built and predicted B-cell epitopes were mapped on the surface of the built model. Our protein subunit was found to be a potential antigen, possessing several antigenic determinants, eliciting antibody. Hence this subunit could be used as a suitable agent for antibody-antigen based diagnostic test. This specific antigen can minimize laboratory errors in identification of A. baumannii and thus help clinicians to quick and precise diagnosis of the bacteria and initiatives to the treatment of the infection. Antigenicity of the region could also be explored for elicitation of antibody to protect the individuals exposed to A. baumannii. PMID- 22079097 TI - Deconvolution of the vestibular evoked myogenic potential. AB - The vestibular evoked myogenic potential (VEMP) and the associated variance modulation can be understood by a convolution model. Two functions of time are incorporated into the model: the motor unit action potential (MUAP) of an average motor unit, and the temporal modulation of the MUAP rate of all contributing motor units, briefly called rate modulation. The latter is the function of interest, whereas the MUAP acts as a filter that distorts the information contained in the measured data. Here, it is shown how to recover the rate modulation by undoing the filtering using a deconvolution approach. The key aspects of our deconvolution algorithm are as follows: (1) the rate modulation is described in terms of just a few parameters; (2) the MUAP is calculated by Wiener deconvolution of the VEMP with the rate modulation; (3) the model parameters are optimized using a figure-of-merit function where the most important term quantifies the difference between measured and model-predicted variance modulation. The effectiveness of the algorithm is demonstrated with simulated data. An analysis of real data confirms the view that there are basically two components, which roughly correspond to the waves p13-n23 and n34-p44 of the VEMP. The rate modulation corresponding to the first, inhibitory component is much stronger than that corresponding to the second, excitatory component. But the latter is more extended so that the two modulations have almost the same equivalent rectangular duration. PMID- 22079098 TI - Enhancement of the male effect on reproductive performance in female Mediterranean goats with long day and/or melatonin treatment. AB - The aim of this study was to determine whether the male effect on reproductive performance in female Mediterranean goats could be enhanced if used in combination with long day and/or melatonin treatments. Thirty-two does were exposed to long days (16 h of light/day) for 95 days. At the end of this period, 16 received one melatonin implant (group LD-M) and 16 did not (group LD). Simultaneously, 16 does under natural photoperiod were implanted with melatonin (group M) or given no treatment (group C, n=16). On April 14th, after 49 days of isolation from males, all does were exposed to bucks fitted with marking harnesses. Oestrous activity, as detected by visual observation, was recorded daily. Transrectal ultrasonography was used to record ovulation, and ovarian activity confirmed by determining plasma progesterone concentration. Oestrous activity, ovulation and fertility were greater in all treatment groups compared with group C (P<0.05), but no differences in ovulation rate or litter size were observed (P>0.05). Productivity (mean number of kids per female) of the LD-M and M groups was significantly greater than in group C (1.50 +/- 0.01 and 1.37 +/- 0.01 vs. 0.69 +/- 0.01 kids, respectively) (P<0.05). Combining melatonin treatment with natural or artificial long days adds to the impact of the male effect. PMID- 22079099 TI - Mapping of VSG similarities in Trypanosoma brucei. AB - The protozoan parasite Trypanosoma brucei switches its variant surface glycoprotein (VSG) to subvert its mammalian hosts' immune responses. The T. brucei genome contains as many as 1600 VSG genes (VSGs), but most are silent noncoding pseudogenes. Only one functional VSG, located in a telomere-linked expression site, is transcribed at a time. Silent VSGs are copied into a VSG expression site through gene conversion. Truncated gene conversion events can generate new mosaic VSGs with segments of sequence identity to other VSGs. To examine the VSG family sub-structure within which these events occur, we combined the available VSG sequences and annotations with scripted BLAST searches to map the relationships among VSGs in the T. brucei genome. Clusters of related VSGs were visualized in 2- and 3-dimensions for different N- and C-terminal regions. Five types of N-termini (N1-N5) were observed, within which gene recombinational events are likely to occur, often with fully-coding 'functional' or 'atypical'VSGs centrally located between more dissimilar VSGs. Members of types N1, N3 and N4 are most closely related in the middle of the N-terminal region, whereas type N2 members are more similar near the N-terminus. Some preference occurs in pairing between specific N- and C-terminal types. Statistical analyses indicated no overall tendency for more related VSGs to be located closer in the genome than less related VSGs, although exceptions were noted. Many potential mosaic gene formation events within each N-terminal type were identified, contrasted by only one possible mosaic gene formation between N-terminal types (N1 and N2). These data suggest that mosaic gene formation is a major contributor to the overall VSG diversity, even though gene recombinational events between members of different N-terminal types occur only rarely. PMID- 22079100 TI - Weekly and 3-weekly cisplatin concurrent with intensity-modulated radiotherapy in locally advanced head and neck squamous cell cancer. AB - In loco-regionally advanced head and neck squamous cell cancer (HNSCC), concurrent 3-weekly cisplatin improves overall survival (OS) compared to radiotherapy alone, but is often associated with renal toxicity. The use of radiotherapy with accelerated fractionation schedules has been reported to improve survival but its optimal combination with chemotherapy is unclear. Retrospective analysis of treatment outcome and nephrotoxicity of radiotherapy given with an intensity-modulated approach (IMRT) concurrent with either 3-weekly or weekly cisplatin in 94 patients with stage III/IV HNSCC. Patients treated with weekly cisplatin were significantly older (p=0.0014) and received a significantly lower total cisplatin dose (p=0.0002). With a median follow-up of 2.8 years, at univariate analysis, 3-weekly cisplatin shows a longer OS (p=0.041) but progression-free survival (PFS) is similar for both schedules (p=0.47). Cisplatin doses >240 mg/m(2) were associated with better OS but not PFS. Chronic renal failure rate was significantly higher with 3-weekly cisplatin (p=0.04). Multivariate analysis (Cox regression controlling for age) confirmed the significant and independent impact of alcohol and smoking habits on both PFS (HR, 2.2) and OS (HR, 2.3), while the treatment schedule affected only OS (HR, 2.2). Weekly cisplatin is less nephrotoxic. Both schedules can be combined to curative IMRT. PFS was not significantly different even if patients treated with the weekly schedule were significantly older and received reduced cisplatin doses. The study suggests that the different cisplatin dose doesn't affect the PFS results if concomitant to IMRT. Controlled prospective studies are needed. PMID- 22079101 TI - [Recurrent cerebral vasospasm: interest of brain tissue oxygen monitoring]. PMID- 22079102 TI - Pulmonary atresia and ventricular septal defect with aortopulmonary collaterals in an adult dog. AB - Pulmonary atresia and ventricular septal defect (PA-VSD) was diagnosed in a 2 year-old castrated male Terrier mix. Transthoracic echocardiography identified a large ventricular septal defect, overriding aorta and severe right ventricular hypertrophy. A main pulmonary artery could not be identified, consistent with pulmonary atresia or persistent truncus arteriosus. Transesophageal echocardiography and angiography confirmed PA-VSD with aortopulmonary collateral circulation arising from the descending thoracic aorta. This case report describes the antemortem diagnosis of the rare congenital defect PA-VSD in an adult dog. PMID- 22079103 TI - Energy and water use by invasive goats (Capra hircus) in an Australian rangeland, and a caution against using broad-scale allometry to predict species-specific requirements. AB - Feral goats (Capra hircus) are ubiquitous across much of Australia's arid and semi-arid rangelands, where they compete with domestic stock, contribute to grazing pressure on fragile ecosystems, and have been implicated in the decline of several native marsupial herbivores. Understanding the success of feral goats in Australia may provide insights into management strategies for this and other invasive herbivores. It has been suggested that frugal use of energy and water contributes to the success of feral goats in Australia, but data on the energy and water use of free-ranging animals are lacking. We measured the field metabolic rate and water turnover rate of pregnant and non-pregnant feral goats in an Australian rangeland during late summer (dry season). Field metabolic rate of pregnant goats (601 +/- 37 kJ kg(-0.73)d(-1)) was 1.3 times that of non pregnant goats (456 +/- 24 kJ kg(-0.73)d(-1)). The water turnover rate of pregnant goats (228 +/- 18 mL kg(-0.79)d(-1)) was also 1.3 times that of non pregnant goats (173 +/- 18 kg(-0.79)d(-1)), but the difference was not significant (P=0.07). There was no significant difference in estimated dry matter digestibility between pregnant and non-pregnant goats (mean ca. 58%), blood or urine osmolality, or urine electrolyte concentrations, indicating they were probably eating similar diets and were able to maintain osmohomeostasis. Overall, the metabolic and hygric physiology of non-pregnant goats conformed statistically to the predictions for non-marine, non-reproductive placental mammals according to both conventional and phylogenetically independent analyses. That was despite the field metabolic rate and estimated dry matter intake of non-pregnant goats being only 60% of the predicted level. We suggest that general allometric analyses predict the range of adaptive possibilities for mammals, but that specific adaptations, as present in goats, result in ecologically significant departures from the average allometric curve. In the case of goats in the arid Australian rangelands, predictions from the allometric regression would overestimate their grazing pressure by about 40% with implications for the predicted impact on their local ecology. PMID- 22079104 TI - Cutaneous water loss and lipids of the stratum corneum in two syntopic species of bats. AB - The lipid matrix of the stratum corneum (SC), the outer layer of the epidermis of mammals and birds, constitutes the barrier to diffusion of water vapor through the skin. The lipids of the SC are structured in the intercellular spaces of the mammalian epidermis in ordered layers, called lamellae, which have been postulated to prevent water loss. Lipids in the mammalian SC are mainly cholesterol, free fatty acids and ceramides, the latter forming the structural support for the lamellae. However, knowledge on how the lipid composition of the SC alters cutaneous water loss (CWL) in mammals is rudimentary, and is largely derived from studies on laboratory animals and humans. We measured CWL of individuals of two species of syntopic bats, Tadarida brasiliensis and Myotis velifer. In the first study of its kind on wild mammals, we correlated CWL with the lipid composition of the SC, measured using thin layer chromatography and high performance liquid chromatography coupled with atmospheric pressure photoionization mass spectrometry. Surface-specific CWL was 20.6% higher in M. velifer than in T. brasiliensis, although differences were not significant. Compared with individuals of M. velifer, individuals of T. brasiliensis had more classes, and a higher proportion, of polar ceramides in the SC, a feature associated with lower CWL. Individuals of T. brasiliensis also had a class of non polar ceramides that presumably spans the lamellae and gives more cohesiveness to the lipid matrix of the SC. We conclude that qualitative and quantitative modifications of the lipid composition of the SC contribute to regulate CWL of these two species of bats. PMID- 22079105 TI - Rhythmic release of prothoracicotropic hormone from the brain of an adult insect during egg development. AB - Prothoracicotropic hormone (PTTH) is a brain neurohormone that has been studied for over 80 years. The only known target of PTTH is the prothoracic glands (PGs) of larvae, which synthesize the insect molting hormones (ecdysteroids) and a massive literature exists on this axis. The PGs degenerate around the time of adult emergence, yet presence of PTTH has been reported in the brains of several adult insects. Using an in vitro bioassay system, we confirm that PTTH is present in the adult female brain of Rhodnius prolixus. The material is electrophoretically, immunologically and biologically indistinguishable from larval PTTH. The amount of PTTH in the brain shows a daily rhythm during egg development. We show that brains in vitro release PTTH with a daily rhythm over this period of time. PTTH is released at each scotophase. This is the first report that PTTH is released from the adult brain and functions as a hormone, inviting explanation of its function. Larval PTTH is also known to be released with a daily rhythm, and the clock in the brain controls both larval and adult rhythms. The potential significance of rhythmic PTTH release in female adults is discussed in relation to the regulation of ecdysteroids, egg development and the concept of internal temporal order. PMID- 22079106 TI - The inhibitory effects of carboxymethyl inulin on the seeded growth of calcium carbonate. AB - Kinetics of precipitation of calcite (CaCO(3)) from aqueous solution in the presence of carboxymethyl inulin (CMI) was investigated under strictly controlled temperature, pH, supersaturation ratio (S=4.8) and ionic strength (I=0.1M). The highly reproducible constant composition technique was used to study the influence of biopolymers of crystal growth of CaCO(3), on CaCO(3) seed crystals at pH 8.5 and 25 degrees C. The crystal growth of calcium carbonate (CaCO(3)) was inhibited in the presence of CMI at low concentration (2.5*10(-9) to 25*10( 9)mol/L). The larger number of negatively charged functional groups exhibited a 95% growth rate inhibition at a concentration of 15*10(-9)mol/L. The higher inhibition efficiency is related to the maximum surface charge density due to adsorbed polymer. PMID- 22079107 TI - Engineering the cytokinin-glucoside specificity of the maize beta-D-glucosidase Zm-p60.1 using site-directed random mutagenesis. AB - The maize beta-D-glucosidase Zm-p60.1 releases active cytokinins from their storage/transport forms, and its over-expression in tobacco disrupts zeatin metabolism. The role of the active-site microenvironment in fine-tuning Zm-p60.1 substrate specificity has been explored, particularly in the W373K mutant, using site-directed random mutagenesis to investigate the influence of amino acid changes around the 373 position. Two triple (P372T/W373K/M376L and P372S/W373K/M376L) and three double mutants (P372T/W373K, P372S/W373K and W373K/M376L) were prepared. Their catalytic parameters with two artificial substrates show tight interdependence between substrate catalysis and protein structure. P372T/W373K/M376L exhibited the most significant effect on natural substrate specificity: the ratio of hydrolysis of cis-zeatin-O-beta-D glucopyranoside versus the trans-zeatin-O-beta-D-glucopyranoside shifted from 1.3 in wild-type to 9.4 in favor of the cis- isomer. The P372T and M376L mutations in P372T/W373K/M376L also significantly restored the hydrolytic velocity of the W373K mutant, up to 60% of wild-type velocity with cis-zeatin-O-beta-D glucopyranoside. These findings reveal complex relationships among amino acid residues that modulate substrate specificity and show the utility of site directed random mutagenesis for changing and/or fine-tuning enzymes. Preferential cleavage of specific isomer-conjugates and the capacity to manipulate such preferences will allow the development of powerful tools for detailed probing and fine-tuning of cytokinin metabolism in planta. PMID- 22079108 TI - Motor inhibition and cognitive flexibility in eating disorder subtypes. AB - Anorexia Nervosa (AN) and Bulimia Nervosa (BN) are complex Eating Disorders (EDs). Even if are considered two different diagnostic categories, they share clinical relevant characteristics. The evaluation of neurocognitive functions, using standardized neuropsychological assessment, could be a interesting approach to better understand differences and similarities between diagnostic categories and clinical subtypes in EDs thus improving our knowledge of the pathophisiology of EDs spectrum. This study explored cognitive flexibility and motor inhibition in patients with AN considering both Restricter and Binge/Purge subtypes, patients with BN and healthy comparisons subjects (HC). Intra-Extra Dimentional Set shifting Test and Stop Signal Task, selected from CANTAB battery, were administered to analyzed set-shifting and motor inhibition respectively. AN patients showed a deficient motor inhibition compared to HC, while no evidence for impaired motor inhibition was found in BN patients; a significant relationship between commission errors in the Stop Signal Task and attentional impulsiveness was found. Moreover, no difference in set-shifting abilities was found comparing all clinician groups and HC. So our results indicated no cognitive impairment in these two cognitive functions in BN patients, while AN and BN showed different performances in motor inhibition. A similar cognitive profile was found in other obsessive compulsive spectrum disorders. Finally, the paper suggests a new interactive approach for the study of cognitive profile in psychiatric disorders; it might be more useful since it is more closely related to the executive functions complexity. PMID- 22079109 TI - Striatal and cortical midline circuits in major depression: implications for suicide and symptom expression. AB - BACKGROUND: In major depression, the neural mechanisms underlying suicide related thoughts and behaviors as well as the expression of other depressive symptoms are incompletely characterized. Evidence indicates that both the striatum and cortical midline structures (CMS) may be involved with both suicide and emotional dysregulation in unipolar illness. The aim of this study was to identify striatal CMS circuits associated with current depression severity and suicidal ideation (SI) as well as a history of self-harm. METHODS: Twenty-two male subjects with recurrent unipolar depression were studied using functional MRI. All subjects were unmedicated and without current psychiatric comorbidity. Correlational analyses were used to determine whether striatal-CMS functional connectivity was associated with any of the three clinical variables. RESULTS: A network involving the bilateral striatum and anterior CMS was found to be associated with depressive symptom severity. Current SI was associated with a similar but less extensive circuit in the left hemisphere. A distinct striatal motor/sensory network was associated with self-harm behaviors, but not current SI or depression severity. CONCLUSIONS: The striatal-anterior CMS circuit likely plays a significant role in the expression of depressive symptoms and SI. In contrast, a striatum-motor/sensory cortex network may be a trait marker of suicide-related behaviors. If replicated, this result might eventually lead to the development of a biomarker that would be useful for studies of pharmacologic and/or psychotherapeutic suicide prevention interventions. PMID- 22079110 TI - Sexually dimorphic fin regeneration in zebrafish controlled by androgen/GSK3 signaling. AB - Certain fish and amphibians regenerate entire fins and limbs after amputation, whereas such potential is absent in birds and limited in mammals to digit tips [1, 2]. Additionally, regenerative success can change during life stages. Anuran tadpoles gradually lose the capacity to regenerate limbs [3, 4], and digit regeneration occurs more effectively in fetal mice and human children than adults [5-8]. Little is known about mechanisms that control regenerative capacity. Here, we identify an unexpected difference between male and female zebrafish in the regenerative potential of a major appendage. Males display regenerative defects in amputated pectoral fins, caused by impaired blastemal proliferation. This regenerative failure emerges after sexual maturity, is mimicked in androgen treated females, and is suppressed in males by androgen receptor antagonism. Androgen signaling maintains expression of dkk1b and igfbp2a, which encode secreted inhibitors of Wnt and Igf signaling, respectively. Furthermore, the regulatory target of Wnts and Igfs, GSK3beta, is inefficiently inactivated in male fin regenerates compared with females. Pharmacological inhibition of GSK3 in males increases blastemal proliferation and restores regenerative pattern. Our findings identify a natural sex bias in appendage regenerative capacity and indicate an underlying regulatory circuit in which androgen locally restricts key morphogenetic programs after amputation. PMID- 22079112 TI - Positional information by differential endocytosis splits auxin response to drive Arabidopsis root meristem growth. AB - In the Arabidopsis root meristem, polar auxin transport creates a transcriptional auxin response gradient that peaks at the stem cell niche and gradually decreases as stem cell daughters divide and differentiate [1-3]. The amplitude and extent of this gradient are essential for both stem cell maintenance and root meristem growth [4, 5]. To investigate why expression of some auxin-responsive genes, such as the essential root meristem growth regulator BREVIS RADIX (BRX) [6], deviates from this gradient, we combined experimental and computational approaches. We created cellular-level root meristem models that accurately reproduce distribution of nuclear auxin activity and allow dynamic modeling of regulatory processes to guide experimentation. Expression profiles deviating from the auxin gradient could only be modeled after intersection of auxin activity with the observed differential endocytosis pattern and positive autoregulatory feedback through plasma-membrane-to-nucleus transfer of BRX. Because BRX is required for expression of certain auxin response factor targets, our data suggest a cell-type specific endocytosis-dependent input into transcriptional auxin perception. This input sustains expression of a subset of auxin-responsive genes across the root meristem's division and transition zones and is essential for meristem growth. Thus, the endocytosis pattern provides specific positional information to modulate auxin response. PMID- 22079111 TI - Ubiquitination of Cdc20 by the APC occurs through an intramolecular mechanism. AB - BACKGROUND: Cells control progression through late mitosis by regulating Cdc20 and Cdh1, the two mitotic activators of the anaphase-promoting complex (APC). The control of Cdc20 protein levels during the cell cycle is not well understood. RESULTS: Here, we demonstrate that Cdc20 is degraded in budding yeast by multiple APC-dependent mechanisms. We find that the majority of Cdc20 turnover does not involve a second activator molecule but instead depends on in cis Cdc20 autoubiquitination while it is bound to its activator-binding site on the APC core. Unlike in trans ubiquitination of Cdc20 substrates, the APC ubiquitinates Cdc20 independent of APC activation by Cdc20's C box. Cdc20 turnover by this intramolecular mechanism is cell cycle regulated, contributing to the decline in Cdc20 levels that occurs after anaphase. Interestingly, high substrate levels in vitro significantly reduce Cdc20 autoubiquitination. CONCLUSION: We show here that Cdc20 fluctuates through the cell cycle via a distinct form of APC-mediated ubiquitination. This in cis autoubiquitination may preferentially occur in early anaphase, following depletion of Cdc20 substrates. This suggests that distinct mechanisms are able to target Cdc20 for ubiquitination at different points during the cell cycle. PMID- 22079113 TI - Mesopelagic cephalopods switch between transparency and pigmentation to optimize camouflage in the deep. AB - Animals in the lower mesopelagic zone (600-1,000 m depth) of the oceans have converged on two major strategies for camouflage: transparency and red or black pigmentation [1]. Transparency conveys excellent camouflage under ambient light conditions, greatly reducing the conspicuousness of the animal's silhouette [1, 2]. Transparent tissues are seldom perfectly so, resulting in unavoidable internal light scattering [2]. Under directed light, such as that emitted from photophores thought to function as searchlights [3-8], the scattered light returning to a viewer will be brighter than the background, rendering the animal conspicuous [2, 4]. At depths where bioluminescence becomes the dominant source of light, most animals are pigmented red or black, thereby reflecting little light at wavelengths generally associated with photophore emissions and visual sensitivities [3, 9-14]. However, pigmented animals are susceptible to being detected via their silhouettes [5, 9-11]. Here we show evidence for rapid switching between transparency and pigmentation under changing optical conditions in two mesopelagic cephalopods, Japetella heathi and Onychoteuthis banksii. Reflectance measurements of Japetella show that transparent tissue reflects twice as much light as pigmented tissue under direct light. This is consistent with a dynamic strategy to optimize camouflage under ambient and searchlight conditions. PMID- 22079114 TI - The origin of phragmoplast asymmetry. AB - The phragmoplast coordinates cytokinesis in plants [1]. It directs vesicles to the midzone, the site where they coalesce to form the new cell plate. Failure in phragmoplast function results in aborted or incomplete cytokinesis leading to embryo lethality, morphological defects, or multinucleate cells [2, 3]. The asymmetry of vesicular traffic is regulated by microtubules [1, 4, 5, 6], and the current model suggests that this asymmetry is established and maintained through treadmilling of parallel microtubules. However, we have analyzed the behavior of microtubules in the phragmoplast using live-cell imaging coupled with mathematical modeling and dynamic simulations and report that microtubules initiate randomly in the phragmoplast and that the majority exhibit dynamic instability with higher turnover rates nearer to the midzone. The directional transport of vesicles is possible because the majority of the microtubules polymerize toward the midzone. Here, we propose the first inclusive model where microtubule dynamics and phragmoplast asymmetry are consistent with the localization and activity of proteins known to regulate microtubule assembly and disassembly. PMID- 22079115 TI - Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo. AB - Although many of the cellular and molecular mechanisms of angiogenesis have been intensely studied [1], little is known about the processes that underlie vascular anastomosis. We have generated transgenic fish lines expressing an EGFP-tagged version of the junctional protein zona occludens 1 (ZO1) to visualize individual cell behaviors that occur during vessel fusion and lumen formation in vivo. These life observations show that endothelial cells (ECs) use two distinct morphogenetic mechanisms, cell membrane invagination and cord hollowing to generate different types of vascular tubes. During initial steps of anastomosis, cell junctions that have formed at the initial site of cell contacts expand into rings, generating a cellular interface of apical membrane compartments, as defined by the localization of the apical marker podocalyxin-2 (Pdxl2). During the cord hollowing process, these apical membrane compartments are brought together via cell rearrangements and extensive junctional remodeling, resulting in lumen coalescence and formation of a multicellular tube. Vessel fusion by membrane invagination occurs adjacent to a preexisting lumen in a proximal to distal direction and is blood-flow dependent. Here, the invaginating inner cell membrane undergoes concomitant apicobasal polarization and the vascular lumen is formed by the extension of a transcellular lumen through the EC, which forms a unicellular or seamless tube. PMID- 22079116 TI - The dynamic range of human lightness perception. AB - Natural viewing challenges the visual system with images that have a dynamic range of light intensity (luminance) that can approach 1,000,000:1 and that often exceeds 10,000:1 [1, 2]. The range of perceived surface reflectance (lightness), however, can be well approximated by the Munsell matte neutral scale (N 2.0/ to N 9.5/), consisting of surfaces whose reflectance varies by about 30:1. Thus, the visual system must map a large range of surface luminance onto a much smaller range of surface lightness. We measured this mapping in images with a dynamic range close to that of natural images. We studied simple images that lacked segmentation cues that would indicate multiple regions of illumination. We found a remarkable degree of compression: at a single image location, a stimulus luminance range of 5,905:1 can be mapped onto an extended lightness scale that has a reflectance range of 100:1. We characterized how the luminance-to-lightness mapping changes with stimulus context. Our data rule out theories that predict perceived lightness from luminance ratios or Weber contrast. A mechanistic model connects our data to theories of adaptation and provides insight about how the underlying visual response varies with context. PMID- 22079117 TI - Validated LC-MS/MS method for the quantitative determination of the glucosylceramide synthase inhibitor miglustat in mouse plasma and human plasma and its application to a pharmacokinetic study. AB - A sensitive liquid chromatography-tandem mass spectrometry method has been developed to quantify miglustat in mouse plasma and in human plasma. The method involved simple protein precipitation with methanol. N-(n-nonyl)deoxynojirimycin was used as internal standard. Separation was performed on a Gemini C18 column (2.1 mm * 50 mm, particle size 5 MUm) with a binary gradient at a flow rate of 600 MUl/min. The mobile phases were methanol and water both containing 0.01% of a 25% ammonium hydroxide solution. The triple stage quadrupole mass spectrometer was operated in APCI mode using the transitions m/z 220.1 >= 158.0 for miglustat and m/z 290.1 >= 228.0 for the internal standard. The method was linear over a range of 10-10,000 ng/ml. The intra-day coefficients of variation for mouse plasma were equal to or smaller than 14.1%. The intra- and inter-day accuracies were 84.5-107.2% and 90.9-104.0%, respectively. For human plasma the intra-day coefficients of variation were equal to or smaller than 13.5%, while accuracies ranged between 93.6% and 100.0%. The validated method offered increased sensitivity (10 times higher) and decreased cycle times compared to other methods. It was successfully applied to the pharmacokinetic assessment of miglustat during treatment of patients with cystic fibrosis. PMID- 22079118 TI - Comparison of high-resolution ultrasonic resonator technology and Raman spectroscopy as novel process analytical tools for drug quantification in self emulsifying drug delivery systems. AB - Self-emulsifying drug delivery systems (SEDDS) are complex mixtures in which drug quantification can become a challenging task. Thus, a general need exists for novel analytical methods and a particular interest lies in techniques with the potential for process monitoring. This article compares Raman spectroscopy with high-resolution ultrasonic resonator technology (URT) for drug quantification in SEDDS. The model drugs fenofibrate, indomethacin, and probucol were quantitatively assayed in different self-emulsifying formulations. We measured ultrasound velocity and attenuation in the bulk formulation containing drug at different concentrations. The formulations were also studied by Raman spectroscopy. We used both, an in-line immersion probe for the bulk formulation and a multi-fiber sensor for measuring through hard-gelatin capsules that were filled with SEDDS. Each method was assessed by calculating the relative standard error of prediction (RSEP) as well as the limit of quantification (LOQ) and the mean recovery. Raman spectroscopy led to excellent calibration models for the bulk formulation as well as the capsules. The RSEP depended on the SEDDS type with values of 1.5-3.8%, while LOQ was between 0.04 and 0.35% (w/w) for drug quantification in the bulk. Similarly, the analysis of the capsules led to RSEP of 1.9-6.5% and LOQ of 0.01-0.41% (w/w). On the other hand, ultrasound attenuation resulted in RSEP of 2.3-4.4% and LOQ of 0.1-0.6% (w/w). Moreover, ultrasound velocity provided an interesting analytical response in cases where the drug strongly affected the density or compressibility of the SEDDS. We conclude that ultrasonic resonator technology and Raman spectroscopy constitute suitable methods for drug quantification in SEDDS, which is promising for their use as process analytical technologies. PMID- 22079119 TI - Leucine limitation regulates myf5 and myoD expression and inhibits myoblast differentiation. AB - Satellite cells are the major pool of muscle stem cells after birth; they represent an important component required to maintain muscle mass and functionality during life. The molecular mechanisms involved in myogenic differentiation are relatively well-known. However, the role of extracellular stimulus in the control of differentiation remains largely unresolved. Notably little is known about the impact of nutrients on this process. Here we have studied the role of leucine, an essential amino acid, in the control of myogenic differentiation. Leucine is a well-known regulator of muscle protein synthesis. It acts not only as a substrate for translation but also as a regulator of gene expression and signaling pathways such as those involving mTOR and GCN2. In this study we demonstrated that the lack of leucine abolishes the differentiation of both C2C12 myoblasts and primary satellite cells. This effect is associated with a modification of the pattern of expression of the myogenic regulatory factors (MRF) myf5 and myoD. We report an up-regulation of myf5 mRNA and a decrease of myoD protein level during leucine starvation. This study demonstrates the importance of a nutrient, leucine, in the control of the myogenic differentiation program. PMID- 22079120 TI - How vitamin A metabolizing dendritic cells are generated in the gut mucosa. AB - CD103(+) dendritic cells (DCs) represent the major migratory DC population in the intestinal lamina propria and are believed to play an essential role in the initiation and regulation of mucosal adaptive immune responses. Small intestine (SI) CD103(+) DCs have an enhanced capacity to generate the vitamin A metabolite, retinoic acid, a property that underlies their ability to induce the gut homing receptors CC chemokine receptor 9 and alpha4beta7 on responding T and B cells, and enhance forkhead box P3(+) T regulatory and IgA plasma cell differentiation in vitro. In this review, we discuss the environmental signals that appear to promote vitamin A metabolising activity in SI CD103(+) DCs in the steady state and thus which may contribute to driving the unique nature of SI immune responses. PMID- 22079121 TI - Can only focusing on physical health make you sick? PMID- 22079122 TI - Direct repair of 3,N(4)-ethenocytosine by the human ALKBH2 dioxygenase is blocked by the AAG/MPG glycosylase. AB - Exocyclic ethenobases are highly mutagenic DNA lesions strongly implicated in inflammation and vinyl chloride-induced carcinogenesis. While the alkyladenine DNA glycosylase, AAG (or MPG), binds the etheno lesions 1,N(6)-ethenoadenine (EA) and 3,N(4)-ethenocytosine (EC) with high affinity, only EA can be excised to initiate base excision repair. Here, we discover that the human AlkB homolog 2 (ALKBH2) dioxygenase enzyme catalyzes direct reversal of EC lesions in both double- and single-stranded DNA with comparable efficiency to canonical ALKBH2 substrates. Notably, we find that in vitro, the non-enzymatic binding of AAG to EC specifically blocks ALKBH2-catalyzed repair of EC but not that of methylated ALKBH2 substrates. These results identify human ALKBH2 as a repair enzyme for mutagenic EC lesions and highlight potential consequences for substrate-binding overlap between the base excision and direct reversal DNA repair pathways. PMID- 22079123 TI - Congenital malignant rhabdoid tumor of the scalp. AB - BACKGROUND: Malignant rhabdoid tumors (MRT) are rare but aggressive tumors presenting in the pediatric population. First thought a variant of Wilms' tumor in the kidney, it is recognized as presenting at renal, central nervous system and other extra-renal primary sites. It is uniformly of very poor prognosis, however. CASE REPORT AND DISCUSSION: We present a case of congenital MRT of the scalp, which we believe to be the first described at this site. The clinical and histopathological features of the tumor are discussed in light of the current literature on MRT at other sites. The bleak prognosis at this site appears to be no different from others - the child succumbed at 10 months old despite surgical resection and initial excellent response to chemotherapy. CONCLUSION: Malignant rhabdoid tumor has a very poor prognosis and needs to be considered in the differential diagnosis of similar lesions by clinicians involved in pediatric head and neck care. PMID- 22079124 TI - Criteria for the request of preoperative tests among oral and maxillofacial surgeons. AB - OBJECTIVE: The aim of this study was to analyze the criteria employed for the requesting of preoperative tests among maxillofacial surgeons. MATERIALS AND METHODS: Thirty maxillofacial surgeons working in Aracaju (Brazil) received a questionnaire to fill out. The study inquired about the practice of requesting preoperative tests for healthy patients scheduled to undergo elective surgery. RESULTS: Most of the surgeons interviewed requested tests that are not recommended for the case in question. The highest frequency of requests was a complete blood count, coagulation test, blood glucose test and chest radiograph. CONCLUSION: The absence of strict rules for the requesting of preoperative tests causes uncertainty and a lack of criteria regarding pre-surgical conduct. It was not possible to clearly define the criteria used by surgeons for requesting such tests, as the clinical characteristics of the hypothetical case presented suggest a smaller number of tests. PMID- 22079125 TI - Distributions of calcitonin gene-related peptide and substance P in the human maxillary sinus of Japanese cadavers. AB - BACKGROUND: Substance P (SP) and calcitonin gene-related peptide (CGRP) are released by the nociceptive sensory nerve and are involved in blood flow, pain and inflammation in the nasal mucosa. The purpose of this study was to assess the distribution of the SP and CGRP nerve fibres related to blood supply within human Schneiderian membrane of the maxillary sinus (MS). MATERIAL AND METHODS: In this study, the MS from Japanese cadavers was examined by whole-mount immunohistochemistry. Human male cadavers (ranging in age from 80 to 90 years) were used in this study. RESULTS: SP- and CGRP-positive fibres were found around large vessels of the medialis superior alveolar branches and also within the floor region of the MS. The floor region of the MS was composed of complex branches of these fibres. CONCLUSION: Our results give useful information for surgical sinus floor elevation in this region of the MS. These anatomical features may assist in the execution of a successful surgical procedure. PMID- 22079126 TI - Evaluation of surgical treatment in mandibular condyle fractures. AB - AIM: In the past, fractures of the mandibular condylar process were, as a rule, treated conservatively. At the Department of Maxillofacial and Oral Surgery of the University Medical Centre Ljubljana, Slovenia, our doctrine was changed in 2002 on the basis of preliminary results and reports in the literature, and these fractures were started to be treated surgically by open reduction and internal fixation with miniplates and screws, which led to good results and a shorter rehabilitation period. The goal of this study was to determine the safety and efficiency of surgical treatment, as well as to compare long-term results of surgical and conservative treatment, as objectively as possible. PATIENTS AND METHODS: Two groups of patients, which had all sustained a unilateral, extra articular mandibular condyle fracture, were compared. In the test group, there were 42 surgically treated patients, and in the control group, 20 conservatively treated patients. Clinical parameters and X-ray images were assessed in both groups and compared by the two tailed Student t test, and in case of attributive variables by the chi(2) test. Within the surgically treated group, postoperative and intraoperative complications were noted: temporary facial nerve palsy, development of a parotid salivary fistula, disturbance of auricle sensibility due to injury of the greater auricular nerve, miniplate fracture, as well as intraoperative bleeding, postoperative haematoma formation, infection, reoperation due to fragment malposition and other complications. Postoperative scars were also assessed. RESULTS: Statistically significant differences between the surgically and conservatively treated patients were found when comparing clinical parameters as well as X-ray images, the results being better in the surgically treated group. Complications of surgical treatment were also noted, the most important among them temporary paresis of facial nerve branches, which occurred in 10 patients (24%). Plate fractures occurred in five patients (12%), in four of them miniplates of sizes less than 2.0mm were used. There were no cases of significant intraoperative bleeding, two cases (5%) required drainage of postoperative haematomas, and one patient (2%) experienced a mild postoperative infection, which was easily controlled with amoxicillin with clavulanic acid. The scar was hidden best if a facelift incision was used, and a hypertrophic scar developed in only one patient (2%). CONCLUSION: Results of surgical treatment of condylar process fractures are superior to the results of conservative treatment, and the procedure is safe with the transparotid surgical approach and adequate surgical technique. PMID- 22079128 TI - Existence, multiplicity and stability of endemic states for an age-structured S-I epidemic model. AB - We study an S-I type epidemic model in an age-structured population, with mortality due to the disease. A threshold quantity is found that controls the stability of the disease-free equilibrium and guarantees the existence of an endemic equilibrium. We obtain conditions on the age-dependence of the susceptibility to infection that imply the uniqueness of the endemic equilibrium. An example with two endemic equilibria is shown. Finally, we analyse numerically how the stability of the endemic equilibrium is affected by the extra-mortality and by the possible periodicities induced by the demographic age-structure. PMID- 22079127 TI - Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: results from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry. AB - OBJECTIVES: The purpose of this study was to describe the prevalence and severity of coronary artery disease (CAD) in relation to prognosis in symptomatic patients without coronary artery calcification (CAC) undergoing coronary computed tomography angiography (CCTA). BACKGROUND: The frequency and clinical relevance of CAD in patients without CAC are unclear. METHODS: We identified 10,037 symptomatic patients without CAD who underwent concomitant CCTA and CAC scoring. CAD was assessed as <50%, >=50%, and >=70% stenosis. All-cause mortality and the composite endpoint of mortality, myocardial infarction, or late coronary revascularization (>=90 days after CCTA) were assessed. RESULTS: Mean age was 57 years, 56% were men, and 51% had a CAC score of 0. Among patients with a CAC score of 0, 84% had no CAD, 13% had nonobstructive stenosis, and 3.5% had >=50% stenosis (1.4% had >=70% stenosis) on CCTA. A CAC score >0 had a sensitivity, specificity, and negative and positive predictive values for stenosis >=50% of 89%, 59%, 96%, and 29%, respectively. During a median of 2.1 years, there was no difference in mortality among patients with a CAC score of 0 irrespective of obstructive CAD. Among 8,907 patients with follow-up for the composite endpoint, 3.9% with a CAC score of 0 and >=50% stenosis experienced an event (hazard ratio: 5.7; 95% confidence interval: 2.5 to 13.1; p < 0.001) compared with 0.8% of patients with a CAC score of 0 and no obstructive CAD. Receiver-operator characteristic curve analysis demonstrated that the CAC score did not add incremental prognostic information compared with CAD extent on CCTA for the composite endpoint (CCTA area under the curve = 0.825; CAC + CCTA area under the curve = 0.826; p = 0.84). CONCLUSIONS: In symptomatic patients with a CAC score of 0, obstructive CAD is possible and is associated with increased cardiovascular events. CAC scoring did not add incremental prognostic information to CCTA. PMID- 22079129 TI - Evaluation of specificity of tuberculosis diagnostic assays in caprine flocks under different epidemiological situations. AB - The aim of this study was to evaluate the specificity of the most widely used tuberculosis (TB) diagnostic tests, single intradermal tuberculin (SIT) and single comparative intradermal tuberculin (SCIT) tests and interferon-gamma (IFN gamma) assay in 937 animals from eight TB-free caprine flocks under different epidemiological situations. Maximum specificity was found using SCIT test (99.4 100% depending on the interpretation criteria) while SIT test and IFN-gamma assay showed a slightly lower overall specificity (97.6-99.2% and 96.4-98.4% respectively). Specificity of the SIT test in a Corynebacterium pseudotuberculosis infected flock was significantly (P<0.05) lower if a severe interpretation criterion was applied. Similarly, specificity values of SIT test and particularly IFN-gamma assay in a paratuberculosis (PTB)-vaccinated flock were lower than those observed in non-vaccinated flocks. Higher proportion of false positive reactors to TB tests (SIT and IFN-gamma assay) were observed among animals positive in the PTB-ELISA in PTB vaccinated flock. These results demonstrate that TB diagnostic tests show an adequate specificity when performed in goats from TB-free flocks in most situations. However, certain factors such as C. pseudotuberculosis infection and paratuberculosis vaccination can have a negative impact in the most sensitive tests. PMID- 22079130 TI - Epilepsy and cerebral palsy: characteristics and trends in children born in 1976 1998. AB - BACKGROUND: Although epilepsy is common in children with cerebral palsy (CP), no data exists on prevalence rates of CP and epilepsy. AIMS: To describe epilepsy in children with CP, and to examine the association between epilepsy and neonatal characteristics, associated impairments and CP subtypes. METHODS: Data on 9654 children with CP born between 1976 and 1998 and registered in 17 European registers belonging to the SCPE network (Surveillance of Cerebral Palsy in Europe) were analyzed. RESULTS: A total of 3424 (35%) children had a history of epilepsy. Among them, seventy-two percent were on medication at time of registration. Epilepsy was more frequent in children with a dyskinetic or bilateral spastic type and with other associated impairments. The prevalence of CP with epilepsy was 0.69 (99% CI, 0.66-0.72) per 1000 live births and followed a quadratic trend with an increase from 1976 to 1983 and a decrease afterwards. Neonatal characteristics independently associated with epilepsy were the presence of a brain malformation or a syndrome, a term or moderately preterm birth compared with a very premature birth, and signs of perinatal distress including neonatal seizures, neonatal ventilation and admission to a neonatal care unit. CONCLUSIONS: The prevalence of CP with epilepsy followed a quadratic trend in 1976-1998 and mirrored that of the prevalence of CP during this period. The observed relationship between epilepsy and associated impairments was expected; however it requires longitudinal studies to be better understood. PMID- 22079131 TI - Atypical onset in a series of 122 cases with FacioScapuloHumeral Muscular Dystrophy. AB - INTRODUCTION: FacioScapuloHumeral Muscular Dystrophy (FSHD), a disease linked to a heterozygous D4Z4 deletion on chromosome 4q35, typically starts with shoulder girdle and facial muscle involvement. Atypical presentations have occasionally been reported, but their frequency has still not been defined. PATIENTS AND METHODS: We studied the occurrence rate of FSHD with atypical onset in 122 symptomatic subjects from 76 unrelated families with genetically confirmed FSHD. These 75 males and 47 females, with a mean age of 49 years (range: 11-85), had a mean EcoRI fragment of 25 kb (range: 11-38). RESULTS: Typical shoulder-girdle or facial weakness at onset was reported by 88 patients (72%). Unusual presentations included: foot drop in 16 (13%) and proximal lower limb weakness in eight patients (7%). Two cases at onset manifested quite atypical, apparently non-FSHD related syndromes: a 42-year-old woman presented with infantile epilepsy and a 41 year-old man with myoglobinuria. In the latter patient, DNA analysis detected a 4q35 deletion associated to an heterozygous CAPN3 mutation. CONCLUSION: FSHD presentation with foot drop or lower limb proximal weakness appeared to be more frequent than expected. This type of weakness at onset has to be considered premature, but still representative of disease-related muscle involvement. Quite atypical onset appears very rare and calls for further investigation on non-FSHD related etiology. PMID- 22079132 TI - [Respiratory and hemodynamic changes during lung recruitment maneuvering through progressive increases and decreases in PEEP level]. AB - OBJECTIVE: To evaluate the respiratory and hemodynamic changes during lung recruitment maneuvering (LRM) through stepwise increases and decreases in PEEP level. DESIGN AND SETTING: A retrospective study in a 17-bed ICU was carried out. PATIENTS: Twenty-one patients with acute respiratory failure and bilateral pulmonary infiltration. INTERVENTION: LRM was carried out, consisting of stepwise increases in PEEP (4 cmH(2)O every 3 minutes), with fixed ventilation pressure, until reaching a maximal value of 36 cmH(2)O PEEP (ascending branch), followed by progressive decreases in PEEP (2 cmH(2)O every 3 minutes) until establishing the open-lung PEEP at the value associated to maximum respiratory compliance (Crs) (descending branch). Continuous hemodynamic monitoring was performed using an esophageal echodoppler probe. RESULTS: Crs gradually decreased in the ascending branch of the LRM, and progressively increased surpassing the initial value after establish the open-lung PEEP in the descending branch, reducing the ventilation pressure and increasing the SpO(2)/FiO(2) ratio. Hemodynamic changes primarily consisted of a fall in cardiac output and left ventricular preload, together with an increased heart rate and cardiac contractility. At comparable levels of PEEP and mean airway pressure, these changes were more pronounced during the descending branch of the LRM. CONCLUSIONS: 1) LRM increased Crs, improving oxygenation and decreasing ventilation pressure; 2) the main hemodynamic consequence was the drop in cardiac output and left ventricular preload; and 3) the unequal hemodynamic derangement in both branches, at the same level of PEEP and mean airway pressure, showed that, along with intrathoracic pressure, other factor such as Crs and hypercapnia may have influenced the hemodynamic consequences of this type of LRM. PMID- 22079133 TI - The electrosurgical knife in an optimized intermittent cutting mode for the endoscopic treatment of benign web-like tracheobronchial stenosis. AB - The established endoscopic treatment of web-like tracheobronchial stenosis is laser vaporization, but the appearance on the market of a new cutting mode with a lower coagulation effect has been proposed as an alternative to laser due to less injury to the tissue. OBJECTIVES: To study the clinical and functional consequences, as well as the side effects of this technique. Afterwards, we investigated whether the use of an electrosurgical knife with this technique is as effective and convenient as an ND-YAG-laser. PATIENTS AND METHODS: Between March 2005 and July 2007, included for study were 22 patients who had undergone 34 interventional bronchoscopy procedures with the VIO-300-D radiofrequency system, using a mode of the Endo-cut I program in conjunction with the reusable knife electrode. RESULTS: All of the patients treated (100%) presented improvements in their symptoms, in the tracheobronchial lumen diameter and in lung function, which were statistically significant. Symptom-free time was 157 +/ 93 days. There was an overall decrease observed in mean obstruction (P<.001). Improvements in FVC (P=.01), Raw (P=.0016) and RV/TLC (P=.01) were significantly significant. Less than 50% of the patients needed a second intervention. These patients were compared retrospectively with a similar group of 22 patients treated with Nd-YAG laser. The follow-up analysis showed that only 18% (4/22) of the patients treated with this new technique presented fibrin, compared with 41% (9/22) of those treated with laser therapy (P<.001). CONCLUSION: The use of this technique is effective for the treatment of benign web-like tracheobronchial stenosis as all the patients showed clinical and functional improvement, and less than 50% required a second intervention. In comparison with laser therapy, an advantage of this technique is that less fibrin is produced, probably due to the reduced anti-coagulation effect. PMID- 22079134 TI - Innate and adaptive immunity in bacteria: mechanisms of programmed genetic variation to fight bacteriophages. AB - Bacteria are constantly challenged by bacteriophages (viruses that infect bacteria), the most abundant microorganism on earth. Bacteria have evolved a variety of immunity mechanisms to resist bacteriophage infection. In response, bacteriophages can evolve counter-resistance mechanisms and launch a 'virus versus host' evolutionary arms race. In this context, rapid evolution is fundamental for the survival of the bacterial cell. Programmed genetic variation mechanisms at loci involved in immunity against bacteriophages generate diversity at a much faster rate than random point mutation and enable bacteria to quickly adapt and repel infection. Diversity-generating retroelements (DGRs) and phase variation mechanisms enhance the generic (innate) immune response against bacteriophages. On the other hand, the integration of small bacteriophage sequences in CRISPR loci provide bacteria with a virus-specific and sequence specific adaptive immune response. Therefore, although using different molecular mechanisms, both prokaryotes and higher organisms rely on programmed genetic variation to increase genetic diversity and fight rapidly evolving infectious agents. PMID- 22079135 TI - Isolation and identification of native membrane glycoproteins from living cell by concanavalin A-magnetic particle conjugates. AB - The discovery, isolation, and subsequent identification of cell membrane glycoproteins involved in the structure and function of the cell surface are becoming more and more important. Here, concanavalin A-magnetic particle conjugates were employed to isolate the special membrane glycoproteins from living HepG-2 cells. The isolated glycoproteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-tandem mass spectrometry as well as annotated. A total of 37 membrane glycoproteins were identified, and 25 of them were ascertained to locate in the extracellular region. PMID- 22079136 TI - Assay of enzymes forming AMP+PPi by the pyrophosphate determination based on the formation of 18-molybdopyrophosphate. AB - The formation of 18-molybdopyrophosphate anion has been studied to develop a simple and rapid assay of the enzymatic reaction involving ATP >AMP+PPi(P(2)O(7)(4-)). By the addition of P(2)O(7)(4-) anion to an acidic acetonitrile-water solution containing MoO(4)(2-) anion, the colorless Mo(VI) solution immediately became yellow due to the formation of 18 molybdopyrophosphate anion. The absorbance of the P(2)O(7)(4-)-Mo(VI) mixture at, for example, 450nm was proportional to the analytical concentration of P(2)O(7)(4 ) anion. Although the test Mo(VI) solution remained colorless by the addition of AMP, it gradually turned to yellow by ATP. The undesired color development is attributed to the formation of a yellow molybdophosphate species accompanied by the dissociation of PO(4)(3-) from the unstable ATP molecule. However, the color development became much slower when ethylenediaminetetraacetic acid was added into an assay mixture, where ATP may form a kinetically stable species. Thus, P(2)O(7)(4-) anion can be determined spectrophotometrically in the enzymatic reaction mixture containing ATP. By the addition of ascorbic acid, the yellow P(2)O(7)(4-)-Mo(VI) mixture turned to blue due to the reduction of the molybdopyrophosphate anion. Thus, P(2)O(7)(4-) anion can be detected colorimetrically by the blueness. The spectrophotometric and colorimetric methods could be applied advantageously to the assay of acetyl-CoA synthetase. PMID- 22079137 TI - Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH sensitive liposomes containing 159Gd-DTPA-BMA in Ehrlich tumor bearing mice. AB - In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the 159Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer. PMID- 22079138 TI - Preparation of complex nano-particles based on alginic acid/poly[(2 dimethylamino) ethyl methacrylate] and a drug vehicle for doxorubicin release controlled by ionic strength. AB - Monodispersed complex nano-particles were synthesized simply by mixing alginic acid (ALG-H) with poly[(2-dimethylamino) ethyl methacrylate] (PDEMA) in pure water without any surfactants or additives. The structure and properties of the nano-particles were extensively studied. The surface charges and average sizes of the nano-particles were varied with the composition of ALG-H and PDEMA. The nano particles were formed through electrostatic attraction force, and they were very stable in pure water, but dissociated in salt solutions. An anticancer drug (doxorubicin) was loaded in the nano-particles and released in different saline solutions. The release profiles revealed that the drug release could be controlled by adjusting the pH and salt concentrations. The nano-particles displayed apparent advantages such as simple preparation process, low cost, free of organic solvents, size controllable, biodegradable and biocompatible. PMID- 22079140 TI - Diagnosis of pneumococcal empyema using immunochromatographic test on pleural fluid and serotype distribution in Korean children. AB - To evaluate the diagnostic value of immunochromatographic test (ICT) on pleural fluid in diagnosing pneumococcal empyema in children and to determine pneumococcal serotypes, 62 exudative parapneumonic effusions from Korean children were tested with culture, ICT for S. pneumoniae, pneumococcal autolysin polymerase chain reaction (PCR), and subsequent sequencing. Of the 62 patients, culture was positive in 3 patients only (4.8%). Pneumococci were identified in 13 samples (21.0%) by sequencing-confirmed PCR and ICT, respectively. When pneumococcal empyema was defined by either positive culture or sequence confirmation, the sensitivity of ICT was 76.9% (10/13) and the specificity of ICT was 93.9%. Eight of 10 patients with positive ICT and culture-negative results had a history of prior antibiotics use, whereas none of the culture-proven cases had. Serotypes of PCR-positive samples were determined by multiplex PCR assays. Multiplex PCR detected serotypes 19A (6), 1 (1), 14 (1), 34 (1), and untypable (4). ICT on pleural fluid is a relatively sensitive and highly specific method for diagnosis of pneumococcal empyema, especially in children given prior antibiotics. PMID- 22079139 TI - [Standardization of the quantification of iron concentration in the liver by magnetic resonance imaging]. AB - OBJECTIVE: To calibrate 1.5 tesla magnetic resonance scanners for the quantification of the concentration of iron in the liver. MATERIAL AND METHODS: We analyzed twenty-eight 1.5 tesla magnetic resonance scanners using a phantom with four tubes containing different concentrations of iron (III) chloride and one tube without iron. The phantom represented two typical patients: one with moderate iron overload and one with high iron overload. We measured the signal intensity ratio between each iron-containing tube and the tube without iron; then we calculated the theoretical levels of iron concentration in each scanner according to the model for the two levels of overload. We compared the results of each scanner with those of the reference scanner in which the model and the phantom had been designed, and we calculated the percentage of difference between the two scanners. RESULTS: The mean difference in the ratios compared to the reference center was 11% (0.3-39). The mean concentration of iron was 71 MUmol Fe/g for moderate overload and 193 MUmol Fe/g for high overload. The mean difference was 6% (1.2- 7%) and 3.4% (0-16%). respectively. In two scanners, we applied a correction factor so that the difference was below 25% in all cases. CONCLUSION: We calibrated twenty-eight 1.5 tesla scanners for the concentration of iron in the liver and achieved variability less than 25%. PMID- 22079141 TI - Infratentorial supracerebellar resection of a pineal tumor using a high definition video exoscope (VITOM(r)). AB - A telescope based high definition (HD) video system (VITOM(r), Karl Storz GmBH & Co., Tuttlingen, Germany) has recently been proposed as an alternative to the operating microscope for microneurosurgery. It remains unclear which clinical situations will benefit from its advantages. In light of the uncomfortable surgeon position and fatigue often associated with pineal region surgery, we used the VITOM(r) HD exoscope system to perform an infratentorial supracerebellar resection of a pineal tumor. The VITOM(r) dramatically improved surgeon comfort and ease of operating by permitting the surgeon to stand upright and in a comfortable position and avoid the need to extend the arm or assume an awkward. position commonly encountered when using the microscope for these approaches. The marked improvement in surgeon comfort afforded by the VITOM(r) exoscope indicates that this system may have significant advantages over traditional microscope based surgery for tumors of the pineal region approached using an infratentorial supracerebellar approach. PMID- 22079142 TI - Cadaveric dissection identifying the left superior anastomotic vein of Trolard communicating indirectly with the superior sagittal sinus via a lateral lacuna. AB - A cadaveric dissection of the calvarium of a 90 year old woman demonstrated a left superior anastomotic vein of Trolard communicating indirectly with the superior sagittal sinus via a left lateral lacunae. This is an anatomical variant contrary to the textbook description of a direct communication between the vein of Trolard and the superior sagittal sinus. A literature search failed to identify a previous description of this variation. Possible clinical implications of this finding will be discussed. PMID- 22079143 TI - Negative reinforcement learning is affected in substance dependence. AB - BACKGROUND: Negative reinforcement results in behavior to escape or avoid an aversive outcome. Withdrawal symptoms are purported to be negative reinforcers in perpetuating substance dependence, but little is known about negative reinforcement learning in this population. The purpose of this study was to examine reinforcement learning in substance dependent individuals (SDI), with an emphasis on assessing negative reinforcement learning. We modified the Iowa Gambling Task to separately assess positive and negative reinforcement. We hypothesized that SDI would show differences in negative reinforcement learning compared to controls and we investigated whether learning differed as a function of the relative magnitude or frequency of the reinforcer. METHODS: Thirty subjects dependent on psychostimulants were compared with 28 community controls on a decision making task that manipulated outcome frequencies and magnitudes and required an action to avoid a negative outcome. RESULTS: SDI did not learn to avoid negative outcomes to the same degree as controls. This difference was driven by the magnitude, not the frequency, of negative feedback. In contrast, approach behaviors in response to positive reinforcement were similar in both groups. CONCLUSIONS: Our findings are consistent with a specific deficit in negative reinforcement learning in SDI. SDI were relatively insensitive to the magnitude, not frequency, of loss. If this generalizes to drug-related stimuli, it suggests that repeated episodes of withdrawal may drive relapse more than the severity of a single episode. PMID- 22079144 TI - Evaluation of the presence of Leishmania spp. by real-time PCR in the lacrimal glands of dogs with leishmaniosis. AB - Leishmania infantum infection is highly prevalent in endemic areas. Dogs with leishmaniosis may develop keratoconjunctivitis sicca (KCS). The goals of this study were (1) to quantify Leishmania amastigotes in the Meibomian glands (MG), main lacrimal gland (MLG) and nictitating membrane gland (NMG) from dogs with leishmaniosis; (2) to compare these results to immunohistochemistry (IHC), and (3) to explore the association between the Leishmania parasite load and the presence of ocular clinical signs. Twenty-five dogs diagnosed with leishmaniosis were included. MG, MLG and NMG from both eyes were collected. Histopathology, IHC and real-time PCR were performed. All specimens yielded positive real-time PCR results. For all three glands, samples from dogs with ocular clinical signs had mean DeltaCt (cycle threshold) values significantly lower (higher parasite loads) than those from dogs without signs. Cut-off values of DeltaCt<0, DeltaCt<4 and DeltaCt<4.9 for MG, MLG and NMG, resulted in a likelihood ratio of positives of 5.9, 6.38 and 6.38, respectively. Samples with DeltaCt values below the reported cut-off were significantly more likely to display clinical signs related to KCS than those with results above the cut-off, for all three glands. Similarly, DeltaCt values below the cut-off were significantly associated with positive IHC. In this study real-time PCR has been standardised for use in MG, MLG and NMG. A cut-off value established for each of these tissues may aid the clinician in the discrimination between ocular signs related to Leishmania from those associated with other causes of KCS. PMID- 22079145 TI - In vivo and ex vivo assessment of the interaction between ivermectin and danofloxacin in sheep. AB - The impact of an efflux pump-related interaction between ivermectin and danofloxacin on their intestinal transport (ex vivo) and disposition kinetics (in vivo) was assessed. Eighteen male Corriedale sheep were randomly assigned to one of three groups. Animals in Group A received 0.2mg/kg ivermectin by SC injection, those in Group B were given 6 mg/kg danofloxacin SC on two occasions 48 h apart and those in Group C were treated with both compounds at the same rates. Plasma concentrations of ivermectin and danofloxacin were measured by HPLC using fluorescence detection. Ex vivo intestinal drug transport activity was measured by the use of the Ussing chamber technique. Plasma concentrations of ivermectin in the first 6 days after injection tended to be higher in Group C than Group A. Contemporaneous treatment with ivermectin significantly increased systemic exposure to danofloxacin (AUC values were 32-35% higher) and prolonged the elimination half-life of danofloxacin (40-52% longer). Ex vivo, incubation with ivermectin significantly decreased the efflux transport of rhodamine 123, a P glycoprotein substrate, in sheep intestine, but no significant effect of danofloxacin on transport activity was observed. Evaluation of the interaction of danofloxacin with the breast cancer resistance protein (BCRP) showed that pantoprazole and ivermectin significantly decreased danofloxacin secretion in the rat intestine. Thus, the ivermectin-induced reduction of danofloxacin efflux transport observed in this study may involve BCRP activity but the involvement of P-glycoprotein cannot be ruled out. PMID- 22079146 TI - Complex polysaccharide inclusions in the skeletal muscle of stranded cetaceans. AB - Skeletal muscle samples were examined post-mortem in 148 cetaceans over a 12-year period. Histological analysis included haematoxylin and eosin (HE) and periodic acid-Schiff (PAS) staining with and without diastase digestion. In addition, histological muscle sections were immunostained for ubiquitin and fast and slow heavy-chain myosin isoforms. PAS-positive, diastase-resistant inclusions were detected in 26 animals from 11 different species. Older cetaceans were preferentially affected. These intrafibre inclusions varied from large aggregates to multiple coarse granules and were typically associated with type II fibres. All diastase-resistant inclusions were positive for ubiquitin. These features resembled those inclusions described as complex polysaccharide in horses. Based on these histological findings and the ubiquitin staining pattern, a morphological diagnosis of complex polysaccharide storage myopathy is proposed. PMID- 22079147 TI - Failure of PFNA: helical blade perforation and tip-apex distance. PMID- 22079148 TI - Monitoring and risk assessment of pesticides in fresh omija (Schizandra chinensis Baillon) fruit and juice. AB - Schizandra chinensis Baillon, or omija, is a fruit native to northeast Asia that is cultivated in South Korea and China. Fresh omija fruit has been used in beverages, traditional East Asian medicine and cosmetics because of its complex flavor and pharmacological effectiveness. The objective of this study was to analyze residue levels of 33 kinds of pesticides on fresh omija fruits and in omija juices produced in South Korea. A risk assessment of the pesticides in omija juice was conducted by calculating EDI and ADI. Most of the pesticide levels were below the LOD in fresh omija fruits. Among the detected compounds, the most frequently detected pesticide was ethoprophos. The EDIs of ethoprophos, pendimethalin and hexaconazole were 5.89E-03, 7.08E-04 and 4.73E-05, respectively. The percent of EDI to ADI of ethoprophos, pendimethalin and hexaconazole was 28.0%, 13.6% and 4.5%, respectively. The results of this research concluded that the detected pesticides are not harmful to human beings. PMID- 22079149 TI - Glycan-modifying bacteria-derived soluble factors from Bacteroides thetaiotaomicron and Lactobacillus casei inhibit rotavirus infection in human intestinal cells. AB - Rotaviruses attach to intestinal cells in a process that requires glycan recognition. Some bacteria from the gut microflora have been shown to modify cell surface glycans. In this study, human intestinal cultured cells were incubated with bacteria-derived soluble factors and infected with rotavirus. Results show that only bacterial soluble factors that increase cell-surface galactose namely, those of Bacteroides thetaiotaomicron and Lactobacillus casei were able to efficiently block rotavirus infections. Increasing cell-surface galactose using galactosyltransferase resulted in a similar blockage of rotavirus infections. These results indicate that manipulation of cell-surface intestinal glycans by bacterial soluble factors can prevent rotavirus infection in a species-specific manner, and should now be considered a potential therapeutic approach against rotavirus infection. PMID- 22079151 TI - Risk of adverse events in treatment-resistant depression: propensity-score matched comparison of antidepressant augment and switch strategies. AB - OBJECTIVE: The objective was to assess differences in adverse events between major depressive patients augmented with a second medication and patients switched to an alternative monotherapy after failing first-step treatment with citalopram. METHOD: Adverse event profiles for second-step switch and augment medication strategies were compared using public data files from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. In the STAR*D trial, participants failing citalopram selected acceptable next-step strategies and were randomized within acceptable strategies. This design resulted in clinically important differences when comparing across strategies, so a propensity-score matched sample was created to compare switch (n=269) and augment (n=269) strategies. RESULTS: Incidence proportions of any adverse event and specific adverse events were similar between the augment and switch groups. The overall incidence proportion of any distressing event was 0.78 [95% confidence interval (CI) 0.72-0.84] in the augment group and 0.80 (95% CI 0.74-0.85) in the switch group. This contrasts unmatched analyses where distressing adverse events were less common in the augment group than the switch group (risk ratio 0.85, 95% CI 0.81-0.90). CONCLUSION: After adjusting for selection bias inherent in the STAR*D comparison of augment with switch, clinically meaningful differences in the adverse event profiles between these treatment strategies were not observed. PMID- 22079150 TI - Nucleoside-diphosphate-kinase: a pleiotropic effector in microbial colonization under interdisciplinary characterization. AB - Emerging evidence identifies multiple roles for nucleoside-diphosphate-kinase in host-microbe interaction. We provide the first synopsis of utilization of this molecule by various microorganisms during colonization of host tissues. Additionally, we propose novel mechanisms this effector may participate in, which could be crucial for microbial adaptation in chronic host infection. PMID- 22079152 TI - Cingulate cortex aplasia and callosal dysgenesia combined with schizencephaly in a patient with chronic lying. AB - We report on a 19-year-old patient with a 4-year history of lying and cheating who presented neuropsychological abnormalities regarding attention deficits, hyperactivity and impulsivity. Cerebral magnetic resonance imaging scans revealed schizencephaly of the right central region, dysgenesia of the corpus callosum, a noneverted gyrus cinguli and hypoplasia of the left cerebellar hemisphere. Although the patient did not fulfill the diagnostic criteria for attention deficit/hyperactivity disorder, we suggest that the patient's behavioral alteration could be related to the neuroanatomical alterations, especially the aplasia of the gyrus cinguli. PMID- 22079153 TI - Partial interruption of axonal transport due to microtubule breakage accounts for the formation of periodic varicosities after traumatic axonal injury. AB - Due to their viscoelastic nature, white matter axons are susceptible to damage by high strain rates produced during traumatic brain injury (TBI). Indeed, diffuse axonal injury (DAI) is one of the most common features of TBI, characterized by the hallmark pathological profiles of axonal bulbs at disconnected terminal ends of axons and periodic swellings along axons, known as "varicosities." Although transport interruption underlies axonal bulb formation, it is unclear how varicosities arise, with multiple sites accumulating transported materials along one axon. Recently, axonal microtubules have been found to physically break during dynamic stretch injury of cortical axons in vitro. Here, the same in vitro model was used in parallel with histopathological analyses of human brains acquired acutely following TBI to examine the potential role of mechanical microtubule damage in varicosity formation post-trauma. Transmission electron microscopy (TEM) following in vitro stretch injury revealed periodic breaks of individual microtubules along axons that regionally corresponded with undulations in axon morphology. However, typically less than a third of microtubules were broken in any region of an axon. Within hours, these sites of microtubule breaks evolved into periodic swellings. This suggests axonal transport may be halted along one broken microtubule, yet can proceed through the same region via other intact microtubules. Similar axonal undulations and varicosities were observed following TBI in humans, suggesting primary microtubule failure may also be a feature of DAI. These data indicate a novel mechanism of mechanical microtubule damage leading to partial transport interruption and varicosity formation in traumatic axonal injury. PMID- 22079154 TI - Overexpression of apolipoprotein E4 increases kainic-acid-induced hippocampal neurodegeneration. AB - Apolipoprotein E (apoE) has an intricate biological function in modulating immune responses and apoE isoforms exhibit diverse effects on neurodegenerative and neuroinflammatory disorders. In the present study, we investigated the individual roles of apoE isoforms in the kainic acid (KA)-induced hippocampal neurodegeneration with focus on immune response and microglia functions. ApoE2, 3 and 4 transgenic mice as well as wild-type (WT) mice were treated with KA by intranasal route. ApoE4 overexpressing mice revealed several peculiarities as compared with other transgenic mice and WT mice, i.e. (1) they had more severe KA induced seizures than apoE2 and 3 mice, (2) they exhibited neuron loss in hippocampus that was higher than in apoE2, 3 and WT mice, (3) KA administration resulted in higher counts of their head drops in the cross-area of elevated plus maze, (4) they showed lower KA-induced rearing activity than apoE2 mice in the open-field test, (5) their KA-induced microglial expression of MHC-II and CD86 was elevated compared to apoE3 mice, (6) the KA-induced increase of microglial iNOS was higher than that in the other groups of mice, and (7) the TNF-alpha and IL-6 expression was decreased 7 days after KA application compared to untreated mice and mice treated 1 day with KA. However, the signaling pathway of NFkappaB or Akt seemed not to be involved in apoE-isoform dependent susceptibility to KA induced neurotoxicity. In conclusion, over-expression of apoE4 deteriorated KA induced hippocampal neurodegeneration in C57BL/6 mice, which might result from a higher up-regulation of microglia activation compared to apoE2 and 3 transgenic mice and WT mice. PMID- 22079155 TI - Pairing tone trains with vagus nerve stimulation induces temporal plasticity in auditory cortex. AB - The selectivity of neurons in sensory cortex can be modified by pairing neuromodulator release with sensory stimulation. Repeated pairing of electrical stimulation of the cholinergic nucleus basalis, for example, induces input specific plasticity in primary auditory cortex (A1). Pairing nucleus basalis stimulation (NBS) with a tone increases the number of A1 neurons that respond to the paired tone frequency. Pairing NBS with fast or slow tone trains can respectively increase or decrease the ability of A1 neurons to respond to rapidly presented tones. Pairing vagus nerve stimulation (VNS) with a single tone alters spectral tuning in the same way as NBS-tone pairing without the need for brain surgery. In this study, we tested whether pairing VNS with tone trains can change the temporal response properties of A1 neurons. In naive rats, A1 neurons respond strongly to tones repeated at rates up to 10 pulses per second (pps). Repeatedly pairing VNS with 15 pps tone trains increased the temporal following capacity of A1 neurons and repeatedly pairing VNS with 5 pps tone trains decreased the temporal following capacity of A1 neurons. Pairing VNS with tone trains did not alter the frequency selectivity or tonotopic organization of auditory cortex neurons. Since VNS is well tolerated by patients, VNS-tone train pairing represents a viable method to direct temporal plasticity in a variety of human conditions associated with temporal processing deficits. PMID- 22079156 TI - Microthrombosis after experimental subarachnoid hemorrhage: time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan. AB - Delayed cerebral ischemia (DCI) is a significant cause of morbidity and mortality for patients surviving the rupture of an intracranial aneurysm. Despite an association between vasospasm and DCI, thrombosis and thromboembolism may also contribute to DCI. In this study we investigate the time course of intravascular microclot formation after experimental subarachnoid hemorrhage (SAH) and assess the effects of the following two drugs on microclot burden: mutant thrombin activated urokinase-type plasminogen activator (scFv/uPA-T), which is bound to red blood cells for use as a thromboprophylactic agent, and clazosentan, an endothelin antagonist. In the first study, adult male C57BL/6 mice were sacrificed at 24 (n=5), 48 (n=6), 72 (n=8), and 96 (n=3) hours after SAH induced by filament perforation of the anterior cerebral artery. Sham animals (n=5) underwent filament insertion without puncture. In the second study, animals received scFv/uPA-T (n=5) 3 hours after hemorrhage, clazosentan (n=5) by bolus and subcutaneous pump after SAH just prior to skin closure, or a combination of scFv/uPA-T and clazosentan (n=4). Control (n=6) and sham (n=5) animals received saline alone. All animals were sacrificed at 48 hours and underwent intra-cardiac perfusion with 4% paraformaldehyde. The brains were then extracted and sliced coronally on a cryostat and processed for immunohistochemistry. An antibody recognizing thrombin-anti-thrombin complexes was used to detect microclots on coronal slices. Microclot burden was calculated for each animal and compared among groups. Following SAH, positive anti-thrombin staining was detected bilaterally in the following brain regions, in order of decreasing frequency: cortex; hippocampus; hypothalamus; basal ganglia. Few microclots were found in the shams. Microclot burden peaked at 48 hours and then decreased gradually. Animals receiving scFv/uPA-T and scFv/uPA-T+clazosentan had a lower microclot burden than controls, whereas animals receiving clazosentan alone had a higher microclot burden (p<0.005). The overall mortality rate in the time course study was 40%; mortality was highest among control animals in the second study. Intravascular microclots form in a delayed fashion after experimental SAH. Microclots may be safely reduced using a novel form of thromboprophylaxis provided by RBC-targeted scFv/uPA-T and represent a potential target for therapeutic intervention in the treatment of DCI. PMID- 22079158 TI - Does frequency matter? ERP and behavioral correlates of monitoring for rare and frequent prospective memory targets. AB - Behavioral and event-related potential (ERP) correlates of monitoring in an event based prospective memory (PM) task were compared during blocks with rare versus frequent PM target presentations relative to an ongoing-task only condition. For both rare and frequent PM conditions, behavioral interference costs in terms of longer reaction times (RTs) were observed. Likewise, during both PM blocks a sustained ERP positivity with a frontal focus was identified on ongoing-task trials. While PM target identification and RT interference costs were larger during the PM-frequent relative to the PM-rare condition, the same sustained frontal positivity was observed during both PM blocks. These findings suggest that successful monitoring is associated with the adoption of a more general prospective retrieval mode, irrespective of target frequency. Moreover, preparatory attentional modulations directed at relevant target features played an important role for subsequent PM performance, as evident in larger P2 amplitudes during PM blocks. PMID- 22079157 TI - Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease. AB - Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of beta-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month-old APP(SweLon)/PS1(M146L), a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared with age-matched control mice. We then developed a method of 3-D microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganization of glucose uptake in relation to cerebral amyloidosis. PMID- 22079159 TI - Pharmacological interference with metabotropic glutamate receptor subtype 7 but not subtype 5 differentially affects within- and between-session extinction of Pavlovian conditioned fear. AB - Fear extinction is defined as the attenuation of a conditioned-fear memory by re exposing animals to the conditioned stimulus without the aversive stimulus. This process is known to be effectively enhanced via administration of D-cycloserine (DCS), a partial NMDA-receptor agonist. However, other glutamatergic mechanisms, such as interference with metabotropic glutamate receptor (mGluR) subtypes 5 and 7 in the extinction of aversive memories are insufficiently understood. Using the allosteric mGluR5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), the mGluR7 allosteric agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), and DCS for comparison, we aimed to study how pharmacological blockade of mGluR5 and activation of mGluR7 influenced within- and between-session conditioned-fear extinction training and extinction retention in rats. We show that when injected before extinction training, mGluR7 activation with AMN082 enhanced freezing and thereby attenuated within-session fear extinction, whereas both DCS and the mGluR5 receptor antagonist MPEP had no effect on this process. However, these differential drug effects were not long lasting, as no difference in extinction retention were observed 24 h later. Therefore, we assessed whether the compounds affect 24 h consolidation of extinction training following incomplete extinction training (between-session extinction). Similar to DCS, AMN082- but not MPEP-treated rats showed facilitated extinction retention, as exhibited by decreased freezing. Finally, using fluoxetine, we provide evidence that the effect of AMN082 on between-session extinction retention is most likely not via increasing 5-HT transmission. These findings demonstrate that mGluR7 activation differentially modulates conditioned fear extinction, in dependence on the protocol employed, and suggests drugs with AMN082-like mechanisms as potential add-on drugs following exposure-based psychotherapy for fear-related human disorders. PMID- 22079160 TI - Deltamethrin, a type II pyrethroid insecticide, has neurotrophic effects on neurons with continuous activation of the Bdnf promoter. AB - Pyrethroids, widely used insecticides with low acute toxicity in mammals, affect sodium channels in neurons. In a primary culture of rat cortical neurons, deltamethrin (DM), a type II pyrethroid, markedly enhanced the expression of brain-derived neurotrophic factor (BDNF) exon IV-IX (Bdnf eIV-IX) mRNA. In this study, we found that DM has a neurotrophic effect on cultured neurons and investigated the mechanisms responsible for it. One MUM DM increased cell survival, neurite complexity and length. Neurite complexity and length were reduced not only by a blockade of cellular excitation with GABA or Ca(2+) influx via L-type voltage-dependent calcium channels with nicardipine, but also by a blockade of TrkB, a specific receptor for BDNF, with TrkB/Fc. These data indicate DM has neurotrophic actions. DM-induced Bdnf eIV-IX mRNA expression through the calcineurin and ERK/MAPK pathways, the increase of which was reduced by GABA(A) receptor activation. Using a promoter assay, we found that Ca(2+)-responsive elements including a CRE are involved in the DM-induced activation of the Bdnf promoter IV (Bdnf-pIV). The intracellular concentration of Ca(2+) and activation of Bdnf-pIV remained elevated for, at least, 1 and 24 h, respectively. Moreover, GABA(A) receptor activation or a blockade of Ca(2+) influx even after starting the incubation with DM reduced the elevated activity of Bdnf-pIV. These data demonstrated that the prolonged activation of Bdnf-pIV occurred because of this continuous increase in the intracellular Ca(2+) concentration. Thus, DM has neurotrophic effects on neurons, likely due to prolonged activation of Bdnf promoter in neurons. This article is part of a Special Issue entitled 'Post Traumatic Stress Disorder'. PMID- 22079161 TI - Retigabine, a K(V)7 (KCNQ) potassium channel opener, attenuates L-DOPA-induced dyskinesias in 6-OHDA-lesioned rats. AB - L-DOPA-induced dyskinesias (LID) represent a severe complication of long-time pharmacotherapy in Parkinson's disease that necessitates novel therapeutics. The acute and chronic effects of K(V)7.2-7.5 channel openers (retigabine, flupirtine) on the severity of LID and parkinsonian signs were examined in comparison to the glutamate receptor antagonist amantadine (positive control) in a rat model of LID. Acute treatment with retigabine (2.5, 5 mg/kg i.p.) and flupirtine (5, 10 mg/kg i.p.) significantly reduced the severity of abnormal involuntary movements (AIM) to a comparable extent as amantadine (20, 40 mg/kg s.c.), but flupirtine delayed the disappearance of AIM. Chronic treatment with retigabine (daily 5 mg/kg i.p. over 19 days combined with l-DOPA 10 mg i.p.) did not prevent or delay the development of LID, but reduced the severity of AIM, while antidyskinetic effects of amantadine (40 mg/kg i.p.) were restricted to the first day of treatment. Retigabine caused sedation and ataxia which declined during the chronic treatment, but did not reduce the antiparkinsonian effects of l-DOPA in these experiments. Acute co-injections of retigabine (5 mg) together with l-DOPA (10 mg/kg) neither reduced the motor performance in the rotarod test nor exerted negative effects on the antiparkinsonian efficacy of l-DOPA in the block and stepping test. Nevertheless, the sedative effects of retigabine may limit its therapeutic potential for the treatment of LID. The present data indicate that K(V)7 channels deserve attention in the research of the pathophysiology of dyskinesias. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22079162 TI - The Anisakis allergy debate: does an evolutionary approach help? AB - Allergic phenomena share common pathways with the immune response against helminth parasites. The definitions regarding allergens and their related concepts have their roots in the area of allergy research. The experience with the fish parasite Anisakis simplex-associated allergic features still nurtures an open debate on the necessity of larvae being alive to induce allergic reactions such as urticaria or anaphylaxis. Conceptual definitions of allergen, major allergen, as well as putatively crossreacting antibodies, as are used in food allergy, depend on the clinical relevance of specific IgE and deserve careful interpretation in the various forms of A. simplex-associated allergic features. Conversely, an evolutionary based interpretation of the presence of specific IgE depends on the viability of A. simplex. PMID- 22079163 TI - What ails Wolbachia transinfection to control disease vectors? PMID- 22079164 TI - The placenta: a main role in congenital toxoplasmosis? AB - Systemic infections, such as toxoplasmosis, acquired during pregnancy can lead to placental infection and have profound effects on the mother-to-child relationship and the success of pregnancy. Placental permeability to Toxoplasma gondii is a main parameter that determines parasite transmission to the foetus, and the use of antibiotics to decrease placental parasite load and prevent congenital toxoplasmosis has been suggested for decades. Although parasitological examination of the placenta at birth is commonly used to diagnose neonatal congenital toxoplasmosis, this approach can be controversial. Here we argue in favour of placental examination for both diagnostic and epidemiological purposes. PMID- 22079165 TI - Photodynamic Antimicrobial Chemotherapy (PACT) in combination with antibiotics for treatment of Burkholderia cepacia complex infection. AB - This study aimed to determine if Photodynamic Antimicrobial Chemotherapy (PACT) was effective in the treatment of Burkholderia cepacia complex infection and whether a synergistic effect was evident if PACT was used in combination with antibiotics. The susceptibility of both planktonic and biofilm cultures of B. cepacia complex strains to methylene blue (MB) and meso-tetra(n-methyl-4 pyridyl)porphine tetra-tosylate (TMP)-mediated PACT was determined alone and in combination with antibiotics used in the treatment of Cystic Fibrosis pulmonary infection caused by these bacteria. When B. cepacia complex strains were grown planktonically, high levels of kill of were achieved with both TMP and MB mediated PACT with strain and photosensitizer specific differences apparent. When strains were grown in biofilm, antibiotic treatment alone was bactericidal in 17/36 (47%) strain/antibiotic combinations tested. When antibiotic treatment was combined with PACT, bactericidal activity was apparent for 33/36 (92%) strain/antibiotic combinations. No antagonism was detected between PACT and antibiotic treatment with the combination synergistic for 6/36 (17%) and indifferent for 30/36 (83%) strain/antibiotic combinations. PACT could be a viable treatment option, either alone or in combination with antibiotics for treatment of B. cepacia complex pulmonary infection. PMID- 22079167 TI - The many faces of aspartate kinases. AB - Based on recent X-ray structures and biochemical characterizations of aspartate kinases from different species, we show in this review how various organizations of a regulatory domain have contributed to the different mechanisms of control observed in aspartate kinases allowing simple to complex allosteric controls in branched pathways. The aim of this review is to show the relationships between domain organization, effector binding sites, mechanism of inhibition and regulatory function of an allosteric enzyme in a biosynthetic pathway. PMID- 22079166 TI - The structure and allosteric regulation of mammalian glutamate dehydrogenase. AB - Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine, while the most important inhibitors include GTP, palmitoyl CoA, and ATP. Recently, spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds were found to block the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme. PMID- 22079168 TI - Minimizing radiation exposure to the vascular surgeon. AB - OBJECTIVES: To determine radiation exposure for members of an endovascular surgery team during imaging procedures by varying technique. METHODS: Digital subtraction angiography imaging of the abdomen and pelvis (Innova 4100; GE, Fairfield, Conn) was performed on cadavers, varying positioning and technique within the usual bounds of clinical practice. Radiation exposure was monitored in real-time with dosimeters (DoseAware; Philips, Andover, Mass) to simulate the position of the operator, assistant, and anesthesiologist. The DoseAware system reports radiation exposure in 1-second intervals. Three to five consecutive data points were collected for each imaging configuration. RESULTS: Operator radiation exposure is minimized with detector-to-patient distance <5 cm (2.1 mSv/h) in contrast to 10 to 15 cm (2.8 mSv/h); source-to-image distance of <15 cm (2.3 mSv/h) in contrast to 25 cm (3.3 mSv/h). Increasing image magnification from 0 (2.3 mSv/h) to 3 (0.83 mSv/h) decreases operator exposure by 74%. Increasing linear image collimation from 0 (2.3 mSv/h) to 10 cm (0.30 mSv/h) decreases operator exposure by 87%. The anesthesiologist's radiation exposure is 11% to 49% of the operator's, greatest in the left anterior oblique (LAO) 90 degree projection. The assistant's radiation exposure is 23% to 46% of the operator's. The highest exposure to the operator was noted to be in the LAO 90 degree projection (30.3 mSv/h) and lowest exposure with 10-cm vertical collimation (0.28 mSv/h). CONCLUSIONS: Varying imaging techniques results in different radiation exposure to members of an endovascular surgery team. Knowledge of the variable intensity of radiation exposure may allow modification of the technique to minimize radiation exposure to the team while providing suitable imaging. PMID- 22079169 TI - In vitro evaluation of the antimicrobial efficacy of a new silver-triclosan vs a silver collagen-coated polyester vascular graft against methicillin-resistant Staphylococcus aureus. AB - OBJECTIVES: Vascular graft infection is a rare but serious complication of vascular reconstructive surgery. This in vitro study investigated the antimicrobial efficacy of a new, silver-triclosan collagen-coated polyester vascular graft compared with a silver collagen-coated polyester vascular graft alone during the first 24 hours. METHODS: The antimicrobial efficacy of the investigated vascular grafts was assessed by performing a time-kill kinetic assay following Clinical and Laboratory Institute Standards-approved guidelines M26-A. For the purpose of the experimental study, the ATCC 33591 strain of methicillin resistant Staphylococcus aureus (American Type Culture Collection, Manassas, Va) was used. All assays were repeated sixfold. Bacterial survival numbers were obtained at 1, 4, 8, 12, and 24 hours using a standard plate count procedure. Bactericidal activity was defined as a 3 log(10) reduction factor (logRF), according to the approved guideline M26-A. RESULTS: Both antimicrobial vascular grafts achieved >3 logRF and fulfilled the efficacy criterion for bactericidal activity but performed differently in their speed of antimicrobial action. The silver-triclosan vascular graft achieved 3.37 logRF after 8 hours, and the silver vascular graft showed a 4.19 logRF after 24 hours. The silver-triclosan graft yielded significantly lower colony-forming units/mL counts after 4 hours compared with the silver graft (4.29 * 10(4) vs 1.03 * 10(6); P = .031). CONCLUSIONS: Both antimicrobial collagen-coated polymer vascular grafts showed bactericidal activity against methicillin-resistant Staphylococcus aureus in vitro. Although the silver-triclosan vascular graft showed a faster antimicrobial efficacy, the silver graft exhibited its antimicrobial properties after 24 hours. Which concept will protect an implanted vascular prosthetic graft better from bacterial contamination and subsequent infection needs to be investigated further in in vivo animal and clinical studies. PMID- 22079170 TI - Two cases of endobronchial carcinoid masked by superimposed aspergillosis: a review of the literature of primary lung cancers associated with Aspergillus. AB - We describe 2 cases of endobronchial pulmonary carcinoid tumor with superimposed Aspergillus colonization. The Aspergillus hyphae were associated with fibrin, ulcer debris, and granulomatous inflammation in part masking the carcinoid tumor. Presence of necrotic debris made diagnosis on biopsy difficult, and atypical carcinoid could not be ruled out. The association of carcinoid tumor with aspergillosis is rare and has been reported in 4 other cases thus far. A review of the literature reveals at least 35 cases of lung carcinoma with coexisting Aspergillus upon presentation. Most of these carcinomas are either cavitary squamous cell or adenocarcinomas harboring an aspergilloma. The other carcinomas are associated with bronchial obstruction as in carcinoids or are a minor component of a preexisting cavity raising the possibility of "scar carcinoma." As in aspergillomas not associated with carcinoma, upper lobe involvement predominates. Diagnosis can be challenging with delayed discovery of underlying neoplasm leading to suboptimal treatment. PMID- 22079171 TI - Correlation between the endoscopic and histologic diagnosis of gastritis. AB - Our aims were to determine the rate of concordance between endoscopic and pathologic diagnoses of gastritis and to determine if there was any common factor in discordant cases. A retrospective analysis of data from 400 patients was performed. The endoscopic diagnoses were compared with the pathologic diagnoses, and histologic slides from discordant cases were reviewed. Of the 400 patients, there was discordance between endoscopy and histology in 136 (34%; kappa statistic, 0.31). These discordant cases comprised 56 with normal endoscopy but abnormal histology and 80 with abnormal endoscopy but normal histology. In 13 patients, there was normal histology, although erosions had been diagnosed endoscopically. No consistent histologic features were found in the discordant cases. These findings show that standard endoscopy is a poor predictor of pathologic changes. Biopsies are required for accurate diagnosis of gastritis. PMID- 22079172 TI - Factors associated with failure to follow-up at a medical clinic after an ED visit. AB - BACKGROUND: Although emergency department (ED) discharge is often based on the presumption of continued care, the reported compliance rate with follow-up appointments is low. STUDY OBJECTIVES: The objectives of this study are to identify factors associated with missed follow-up appointments from the ED and to assess the ability of clinicians to predict which patients will follow-up. METHODS: Patients without insurance or an outpatient primary care provider (PCP) were given a follow-up clinic appointment before discharge. Information identifying potential follow-up barriers was collected, and the physician's perception of the likelihood of follow-up was recorded. Patients who missed their appointment were contacted via telephone and were offered a questionnaire and a rescheduled clinic appointment. RESULTS: A total of 125 patients with no PCP were enrolled. Sixty (48%; 95% confidence interval, 39-57) kept their scheduled appointment. Sex, distance from clinic, availability of transportation, or time since last nonemergent physician visit was associated with attendance to the follow-up visit. Clinicians were unable to predict which patients would follow up. Contact by telephone was made in 48 (74%) of patients who failed to follow up. Of the 14 patients willing to reschedule, none returned for follow-up. CONCLUSION: Among ED patients who lack a PCP and are given a clinic appointment from the ED, less than half keep the appointment. Moreover, clinicians are unable to predict which patients will follow up. This study highlights the difficulty in maintaining continuity of care in populations who are self-pay or have Medicaid and lack regular providers. This may have implications on discharge planning from the ED. PMID- 22079173 TI - Clinical protection, sub-clinical infection and persistence following vaccination with extinction payloads of O1 Manisa Foot-and-Mouth Disease monovalent vaccine and challenge in goats and comparison with sheep. AB - Small ruminants play an important role in the epidemiology of Foot-and-Mouth Disease (FMD). Small ruminants are vaccinated with one-half or one-third of cattle dose of oil-based or aqueous vaccines respectively. The extinction antigen payload in vaccine for protection in small ruminants is poorly studied. FMD seronegative Nellore sheep (n=30) and Osmanabadi goats (n=30) were vaccinated with different payloads of O(1) Manisa vaccine (0.45-5 MUg). Vaccinated and sero negative unvaccinated sheep (n=6) and goats (n=6) were challenged intradermally into the coronary band with O(1) Manisa virus. The sheep and goats were monitored for signs of FMD and samples were collected for measuring viraemia and virus associated with nasal swabs and probang samples. Clotted blood was collected for serology. Vaccines containing antigen payload up to 0.94 MUg protected sheep and goats against challenge. Sheep and goats vaccinated with 0.45 MUg antigen payload were poorly protected against challenge. An antigen payload of 0.94 MUg was sufficient to offer complete protection and also absence of carrier status. Sheep and goats with no vaccination or with poor sero conversion to vaccination showed sub-clinical infection and became carriers. The results of the study suggest that vaccination offers protection from clinical disease even at a low payload of 0.94 MUg and hence one-half of cattle dose of the oil-based vaccine formulations is sufficient to induce protective immune response in sheep and goats. Since no live virus could be isolated after 5 days post challenge from the nasal swab or probang samples even though viral RNA was detected, the risk of these animals transmitting disease was probably very low. PMID- 22079174 TI - Residual transglutaminase in collagen - effects, detection, quantification, and removal. AB - In the present study, we developed an enzyme-linked immunosorbent assay (ELISA) for microbial transglutaminase (mTG) from Streptomyces mobaraensis to overcome the lack of a quantification method for mTG. We further performed a detailed follow-on-analysis of insoluble porcine collagen type I enzymatically modified with mTG primarily focusing on residuals of mTG. Repeated washing (4 *) reduced mTG-levels in the washing fluids but did not quantitatively remove mTG from the material (p < 0.000001). Substantial amounts of up to 40% of the enzyme utilized in the crosslinking mixture remained associated with the modified collagen. Binding was non-covalent as could be demonstrated by Western blot analysis. Acidic and alkaline dialysis of mTG treated collagen material enabled complete removal the enzyme. Treatment with guanidinium chloride, urea, or sodium chloride was less effective in reducing the mTG content. PMID- 22079175 TI - Nuclear mechanics in differentiation and development. AB - The nucleus is by far one of the stiffest organelles within cells of higher eukaryotes. Its mechanical properties are determined by contributions from the nuclear lamina and chromatin. Together they allow a viscoelastic response of the nucleus to applied stresses, where the lamina is thought to behave as an elastic shell, while the nucleoplasm contributes as a largely viscous material. Nuclear mechanics changes during differentiation and development. Altered nuclear mechanics reflects but might also influence global re-arrangements in chromatin architecture, which take place when cells commit themselves into distinct lineages. Thus it is likely that the mechanical characteristics of nuclei significantly contribute to proper differentiation. PMID- 22079176 TI - Evaluation of portable Raman spectrometer with 1064 nm excitation for geological and forensic applications. AB - The development of miniaturized Raman instrumentation is in demand for applications relevant to forensic, pharmaceutical and art analyses, as well as geosciences, and planetary exploration. In this study we report on evaluation of a portable dispersive Raman spectrometer equipped with 1064 nm laser excitation. Selected samples from geological, geobiological and forensic areas of interest have been studied from which the advantages, disadvantages and the analytical potential of the instrument are assessed based on a comparison with bench instrumentation and other portable Raman spectrometers using 785 nm excitation. It is demonstrated that the instrument operating with 1064 nm excitation has potential for expanding the number and types of samples that can be measured by miniaturized Raman spectroscopy without interfering fluorescence background emission. It includes inorganic and organic minerals, biomolecules within living lichen and endolithic cyanobacteria as well as drugs of abuse and explosives. PMID- 22079178 TI - Application of the Theory of Planned Behaviour to weight control in an overweight cohort. Results from a pan-European dietary intervention trial (DiOGenes). AB - Using the Theory of Planned Behaviour (TPB), this study investigates weight control in overweight and obese participants (27 kg/m(2)<=BMI<45 kg/m(2)) taking part in a dietary intervention trial targeted at weight loss maintenance (n=932). Respondents completed TPB measures investigating "weight gain prevention" at three time points. Correlation and regression analyses were used to investigate the relationship between TPB variables and weight regain. The TPB explained up to 27% variance in expectation, 14% in intention and 20% in desire scores. No relationship was established between intention, expectation or desire and behaviour at Time 1 or Time 2. Perceived need and subjective norm were found to be significantly related to weight regain, however, the model explained a maximum of 11% of the variation in weight regain. Better understanding of overweight individuals' trajectories of weight control is needed to help inform studies investigating people's weight regain behaviours. Future research using the TPB model to explain weight control should consider the likely behaviours being sought by individuals. PMID- 22079177 TI - An alpha-lactalbumin-enriched and symbiotic-supplemented v. a standard infant formula: a multicentre, double-blind, randomised trial. AB - The aim of the present study was to evaluate the safety, tolerance and preventive effect on atopic dermatitis of an experimental alpha-lactalbumin-enriched and symbiotic-supplemented infant formula. A total of ninety-seven non-breastfed term neonates were enrolled into a double-blind, multicentre, randomised controlled trial in which they received experimental (n 48) or standard formula (n 49) for 6 months. The primary outcome was weight at 6 months of age. Secondary outcomes were gastrointestinal tolerance and manifestation of atopic dermatitis. Faecal secretory IgA (SIgA) concentration and microbiota composition of forty-three infants were analysed at 1 and 6 months. Growth was similar in both groups. At 1 month, compared to those in the control group, infants in the experimental group exhibited less crying or agitation, and more quiet behaviour (P=0.03). At 6 months, atopic dermatitis was less frequently observed in the experimental group (P<0.05). Decrease of faecal SIgA concentration between 1 and 6 months was mainly observed in the control group. This decrease was significantly associated with atopic dermatitis (P<0.014) and negatively correlated to the level of colonisation by bifidobacteria (P<0.005). In conclusion, compared to the control formula, the experimental formula guaranteed a similar growth, was better tolerated at 1 month and had a protective effect against the development of atopic dermatitis. PMID- 22079179 TI - Evolution of neutrophil apoptosis in septic shock survivors and nonsurvivors. AB - PURPOSE: The aims were to analyze the temporal evolution of neutrophil apoptosis, to determine the differences in neutrophil apoptosis among 28-day survivors and nonsurvivors, and to evaluate the use of neutrophil apoptosis as a predictor of mortality in patients with septic shock. MATERIALS AND METHODS: Prospective multicenter observational study carried out between July 2006 and June 2009. The staining solution study included 80 patients with septic shock and 25 healthy volunteers. Neutrophil apoptosis was assessed by fluorescein isothiocyanate (FITC)-conjugated annexin V and aminoactinomycin D staining. RESULTS: The percentage of neutrophil apoptosis was significantly decreased at 24 hours, 5 days, and 12 days after the diagnosis of septic shock (14.8% +/- 13.4%, 13.4% +/- 8.4%, and 15.4% +/- 12.8%, respectively; P < .0001) compared with the control group (37.6% +/- 12.8%). The difference in apoptosis between 28-day surviving and nonsurviving patients was nonsignificant (P > .05). The mortality rate at 28 days was 53.7%. The crude hazard ratio for mortality in patients with septic shock did not differ according to the percentage of apoptosis (hazard ratio, 1.006; 95% confidence interval, 0.98-1.03; P = .60). CONCLUSIONS: During the first 12 days of septic shock development, the level of neutrophil apoptosis decreases and does not recover normal values. No differences were observed between surviving and nonsurviving patients. PMID- 22079180 TI - Etiological diagnosis of left ventricular dysfunction: computed tomography compared with coronary angiography and cardiac magnetic resonance. AB - INTRODUCTION AND OBJECTIVES: To evaluate the capability of multidetector computed tomography to diagnose the coronary etiology of left ventricular dysfunction compared with using invasive coronary angiography and magnetic resonance. METHODS: Forty consecutive patients with left ventricular dysfunction of uncertain etiology underwent invasive coronary angiography and contrast magnetic resonance. All patients were evaluated with multidetector computed tomography including coronary calcium presence and score, noninvasive coronary angiography, and myocardial tissue assessment. RESULTS: The sensitivity and specificity of the presence of coronary calcium to identify left ventricular dysfunction was 100% and 31%, respectively. If an Agatston calcium score of >100 is taken, specificity increases to 58% with sensitivity still 100%. Sensitivity and specificity for coronary angiography by multidetector computed tomography was 100% and 96%, respectively; for identifying necrosis in contrast acquisition it was 57% and 100%, respectively; and in late acquisition, 84% and 96%, respectively. To identify coronary ventricular dysfunction with necrosis, the sensitivity and specificity was 92% and 100%, respectively. CONCLUSIONS: Of all the diagnostic tools available in multidetector computed tomography, coronary angiography is the most accurate in determining the coronary origin of left ventricular dysfunction. A combination of coronary angiography and myocardial tissue study after contrast allows a single test to obtain similar information compared with the combination of invasive coronary angiography and contrast magnetic resonance. PMID- 22079181 TI - Polycyclic aromatic hydrocarbon levels in three pelagic fish species from Atlantic Ocean: inter-specific and inter-season comparisons and assessment of potential public health risks. AB - The concentrations of 18 polycyclic aromatic hydrocarbons (PAHs) were determined in three commercially valuable fish species (sardine, Sardina pilchardus; chub mackerel, Scomber japonicus; and horse mackerel, Trachurus trachurus) from the Atlantic Ocean. Specimens were collected seasonally during 2007-2009. Only low molecular weight PAHs were detected, namely, naphthalene, acenaphthene, fluorene and phenanthrene. Chub mackerel (1.80-19.90MUg/kgww) revealed to be significantly more contaminated than horse mackerel (2.73-10.0MUg/kgww) and sardine (2.29 14.18MUg/kgww). Inter-specific and inter-season comparisons of PAHs bioaccumulation were statistically assessed. The more relevant statistical correlations were observed between PAH amounts and total fat content (significant positive relationships, p?0.05), and season (sardine displayed higher amounts in autumn-winter while the mackerel species showed globally the inverse behavior). The health risks by consumption of these species were assessed and shown to present no threat to public health concerning PAH intakes. PMID- 22079182 TI - Induction of uncoupling protein-1 and -3 in brown adipose tissue by kaki-tannin in type 2 diabetic NSY/Hos mice. AB - Kaki-tannin, a highly polymerized-tannin from the young fruits of persimmon (Diospyros kaki 'Hachiya'), has been shown to have bile acid-binding activity. To verify the effect of kaki-tannin on the metabolism of lipid and glucose in type 2 diabetes, type 2 diabetic NSY/Hos mice were fed an AIN76-modified high fat diet supplemented with 1% (w/w) kaki-tannin for 8weeks. Kaki-tannin induced a 2-fold increase in fecal bile acid excretion and was significantly effective in the prevention of a rise in plasma cholesterol, triglyceride, and insulin levels. Kaki-tannin treatment also prevented fatty liver. To identify the molecular mechanism underlying these effects, gene expression analysis was performed on liver, brown adipose tissue (BAT), and skeletal muscle. The genes related to cholesterol metabolism, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein 2, were increased in the liver of the kaki-tannin group. Interestingly, the uncoupling protein-1 (UCP1) gene and the UCP3 gene were significantly increased in the BAT of the kaki-tannin group, which was also confirmed at the protein level. These findings indicated that induction of UCP1 and UCP3 in the BAT by kaki-tannin treatment might influence the energy metabolism, thus contributing beneficial effects to type 2 diabetic NSY/Hos mice. PMID- 22079183 TI - The effects of chronic aluminum exposure on learning and memory of rats by observing the changes of Ras/Raf/ERK signal transduction pathway. AB - OBJECTIVE: To investigate the effects of chronic aluminum (Al) exposure on learning and memory function of rats by observing the changes of Ras/Raf/ERK (Ras/ERK) signaling pathway. METHODS: Eighty weaned Wistar rats were divided into four groups ad libitum, 20 rats in each group. The four groups were fed with drinking water containing 0% (control), 0.2%, 0.4% and 0.6% (Al exposure) AlCl(3) for 3months individually to set up aluminum exposure models. The laboratory was maintained at 18-23 degrees C and 45-55% relative humidity. Graphite furnace atomic absorption spectrometry was used to detect the content of Al in brain and blood. Western blot and real-time PCR (RT-PCR) were used to determine the protein and mRNA expression levels for Ras, Raf1, ERK2 and CREB. RESULTS: Chronic Al exposure increased the content of Al in rats' blood and brain. It increased expression of Ras in the hippocampi compared with the control but the expression decreased along the Al exposure groups (p<0.05). Similarly, Raf1, ERK2 and CREB expressions decreased compared to the control in a dose-dependent manner (p<0.05). CONCLUSION: Chronic Al exposure may affect learning and memory through impact on Ras/ERK signal pathway. PMID- 22079184 TI - Study of the potential toxicity of commercial crispy breads by evaluation of bioaccessibility and bioavailability of minor Fusarium mycotoxins. AB - Enniatins (ENs) are bioactive compounds produced by the secondary metabolism of several Fusarium strains and known to have several biological activities, such as acting as enzyme inhibitors, antifungal and antibacterial agents, and immunomodulatory substances. This study has investigated the ENs bioaccessibility, spiked in commercial wheat crispy bread at 1.5 and 3.0MUmol/g concentrations, their transepithelial transport and bioavailability using Caco-2 cells as a model of the human intestinal epithelium. The content (%) of the four ENs contained in the gastric fluid has resulted variable from 69% to 91%, considering the two concentrations assayed. The mean bioaccessibility data for the compounds studied, resulted of 80%. The compounds that evidenced the highest absorption, using the in vitro model which simulated the transepithelial transport, were the EN A (70.8+/-1.3% of absorption) and A(1) (73.8+/-0.9%) at 1.5 and 3.0MUmol/g concentrations, respectively. The compound with the lowest transport value (50.7+/-1.3%) was the EN A at 3.0MUmol/g concentration. The bioavailability data evidenced by the other ENs employed ranged from 55.2+/-1.1% to 66.1+/-1.0%. PMID- 22079185 TI - Enhanced degradation of trichloroethylene in nano-scale zero-valent iron Fenton system with Cu(II). AB - Degradation of trichloroethylene (TCE) in nano-scale zero-valent iron (nZVI) Fenton system with Cu(II) was investigated in a closed batch system. TCE was significantly degraded (95%) in 10 min in nZVI Fenton system with 20mM Cu(II) at initial pH 3, while slight degradation (25%) was observed in nZVI Fenton system without Cu(II) at the same experimental condition. Aqueous Fe(II) concentration proportionally increased (1.2-19.6mM) with increasing Cu(II) concentration (1 20mM). Surface analyses using X-ray spectroscopy showed that metallic Cu was formed on the nZVI surface and surface Fe(0) decreased by 1.4 times after the addition of Cu(II) to nZVI suspension. Kinetic rate constant for TCE degradation at 15.3mM nZVI (4.1989 min(-1)) increased by 1.8 times till the increase of nZVI concentration by 5 times and then showed a saturation pattern at higher nZVI concentration. As Cu(II) concentrations increased in the Cu/nZVI Fenton system, the rate constant increased linearly (R(2)=0.979). No significant difference has been observed in the degradation kinetics of TCE by Cu/nZVI Fenton at pH 3 and pH 6 (4.8720 min(-1) vs. 4.9858 min(-1)), whereas the kinetics by nZVI Fenton at pH 6 were 1.6 times faster (0.0318 min(-1)) than at pH 3 (0.0194 min(-1)). PMID- 22079186 TI - Photo-Fenton degradation of the insecticide esfenvalerate in aqueous medium using a recirculation flow-through UV photoreactor. AB - The aim of the study was to evaluate the efficiencies of photo-Fenton (Fe(2+)) and (Fe(3+)) processes in the degradation of high-concentrations of esfenvalerate (in the form of aqueous emulsion of a commercial formulation) using a recirculation flow-through photoreactor irradiated with UV light from a 15 W lamp (254 nm emission peak). The results obtained using a basic photo-Fenton (Fe(2+)) reaction (esfenvalerate 17 mg L(-1); ferrous sulphate 1 mM; hydrogen peroxide 25 mM; pH 2.5) were compared with those acquired when ferrioxalate (1, 3 or 5 mM) served as the iron source. Degradation of the active component of the commercial formulation was significantly greater, and the rate of oxidation more rapid, using a photo-Fenton (Fe(3+)) process compared with its Fe(2+) counterpart. The most efficient degradation of the insecticide (75% in 180 min) was achieved with a reaction mixture containing 5mM ferrioxalate. However, under the same experimental conditions, degradation of pure esfenvalerate preceded much faster (99% in 60 min) and was 100% complete within 180 min reaction time. PMID- 22079187 TI - Novel KMnO4-modified iron oxide for effective arsenite removal. AB - This work demonstrates the synthesis of a novel KMnO(4)-modified form of iron oxide, MnBT-4, using a fluidized bed reactor (FBR) for the adsorptive removal of arsenic (III)/(V). Characterization by XRD, BET, and SEM indicated that the BT-4 support was poorly crystallized goethite (alpha-FeOOH) with a specific surface area of 229 m(2) g(-1). In FBR experiments of synthesizing MnBT-4, the Fe and Mn salts were found to have an optimal dosage ratio of less than 4, which maximized the KMnO(4) immobilization efficiency. The immobilized Mn compounds on MnBT-4 underwent an additional oxidation step of As (III), promoting arsenic adsorption. When applied MnBT-4 for As (III) removal from solution, the sorption isotherm was accurately fitted with Langmuir and Freundlich models, while the maximum adsorption capacity of 27.4 mg g(-1) exceeded those of other adsorbents in the literature. Batch experimental results revealed that both raw BT-4 and MnBT-4 could take up a large amount of As (V). However, the MnBT-4 provided a substantially higher As (III) removal efficiency than BT-4. PMID- 22079188 TI - Stabilization of nickel-laden sludge by a high-temperature NiCr2O4 synthesis process. AB - The feasibility of stabilizing nickel-laden sludge by a high-temperature NiCr(2)O(4) synthesis process was investigated with different sintering temperatures, salt contents, molar ratios, and reaction atmospheres. The crystalline phases of species were investigated by using an X-ray diffraction, and the surface characteristics of particles were observed by scanning electron microscopy. The leaching behavior of the stabilized sludge was evaluated by Toxicity Characteristic Leaching Procedure (TCLP) test. The results indicated that NiCr(2)O(4) was formed at around 800 degrees C by transforming NiO and Cr(2)O(3) into a spinel structure. Leaching concentrations of both nickel and chromium decreased with an increase in the sintering temperature. The existence of salt in the sludge disturbed the formation of spinel, but a moderate salt content contributed to stabilization efficiency. A Cr/Ni molar ratio >2 also contributed to the stabilization efficiency of heavy metals after the thermal process. NiCr(2)O(4) was transformed from simulated sludge under both an N(2) and air atmosphere. The sintering strategy designed for nickel-laden sludge was proven to be beneficial in stabilizing nickel and chromium. PMID- 22079190 TI - Residual structure and dynamics in DMSO-d6 denatured dynein light chain protein. AB - Structural and motional features in the denatured state of a protein dictate the early folding events starting from that state and these features vary depending upon the nature of the denaturant used. Here, we have attempted to decipher the early events in the folding of Dynein Light Chain protein (DLC8), starting from DMSO-d6 denatured state. Multinuclear NMR experiments were used to obtain the full spectral assignment. The HSQC spectrum shows the presence of two sets of peaks for the residues Met 1, Ser 2, Arg 4, Ala 11, Met 17, Thr 26, Lys 44, Tyr 50, Asn 51, Trp 54, His 55, Val 58, Gly 59, Ser 64, Tyr 65, His 68, Phe 86, Lys 87 indicating the presence of slow conformational transition in the heterogeneous ensemble. Analysis of residual structural propensities with secondary (13)C chemical shifts, (3)J(H(N)(-)H(alpha)) coupling constants and (1)H-(1)H NOE revealed the presence of local preferences which encompass both native and non native like structures. The spectral density calculations, as obtained from measured R(1), R(2) and (1)H-(15)N steady state NOE values provide insights into the backbone dynamics on the milli to picosecond timescale. The segment Ser 14 - His 55 exhibits slow motions on the milli- to microsecond timescale arising from conformational exchange. The presence of native like structural preference, as well as conformational exchange classifies the above segment as the nucleation site of folding. Based on the observations, we propose here, the probable hierarchy of folding of DLC8 on dilution of denaturant: the two helices are formed first followed by the formation of beta2 and beta5. PMID- 22079189 TI - The ATM protein kinase and cellular redox signaling: beyond the DNA damage response. AB - The ataxia-telangiectasia mutated (ATM) protein kinase is best known for its role in the DNA damage response, but recent findings suggest that it also functions as a redox sensor that controls the levels of reactive oxygen species in human cells. Here, we review evidence supporting the conclusion that ATM can be directly activated by oxidation, as well as various observations from ATM deficient patients and mouse models that point to the importance of ATM in oxidative stress responses. We also discuss the roles of this kinase in regulating mitochondrial function and metabolic control through its action on tumor suppressor p53, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and hypoxia-inducible factor 1 (HIF1), and how the regulation of these enzymes may be affected in ATM-deficient patients and in cancer cells. PMID- 22079191 TI - Getting the most out of your IP--patent management along its life cycle. AB - Effectively managing and optimizing the value of the patent portfolio is a major challenge for many firms, especially those in knowledge intensive industries, such as the pharmaceutical, biotechnological and chemical industry. However, insights on effective patent portfolio strategies are rare. Therefore, in this article we investigate in detail how firms successfully manage and optimize their patent portfolios to increase their overall competitiveness. We discover that successful patent portfolio management is rooted in managing the patents along their life cycles. Based on the findings of ten case studies, we develop a holistic patent life cycle management model reflecting five distinctive phases of patent management: explore, generate, protect, optimize and decline. We conclude with how our findings can be used in practice. PMID- 22079192 TI - Intrathecally synthesized IgG in multiple sclerosis cerebrospinal fluid recognizes identical epitopes over time. AB - Intrathecal antibody production manifest as oligoclonal bands (OCBs) is a hallmark of multiple sclerosis (MS). Once present, OCBs can be detected in CSF throughout the lifetime of MS patients. To determine the specificity of the OCBs, we applied CSF IgG obtained from 2 consecutive lumbar punctures of 5 MS patients to screen phage-displayed random peptide libraries, and selected identical and related peptides that reacted with the paired CSF IgGs from each patient. Highly sensitive phage-mediated immuno-PCR revealed that the phage peptides bound specifically to IgG in MS CSF collected over time. IEF immunoblots also showed that these peptides were recognized by OCBs in MS CSF. We further demonstrated that the peptides represented linear epitopes, indicating that they represent natural epitopes of corresponding protein antigens. A database search combined with alanine scan mutagenesis of peptides that bound to CSF IgG from 3 MS patients revealed that they are derived from proteins including serine/threonine protein kinase, protein ZIP2 and MHC class II. Identification of epitopes that are recognized by IgG in MS CSF over time provides a critical tool to investigate the specificity of OCBs, which may determine the cause of disease, leading to strategies for diagnostic and therapeutic intervention. PMID- 22079193 TI - Human T-cell responses to botulinum neurotoxin. Responses in vitro of lymphocytes from patients with cervical dystonia and/or other movement disorders treated with BoNT/A or BoNT/B. AB - We have previously reported that botulinum neurotoxin type A (BoNT/A)-specific T cell responses occur in a majority of patients treated with botulinum neurotoxins (BoNT). In this study, we first determined if T-cell responses against BoNT/A and tetanus toxin (TeNT) differ between cervical dystonia (CD) patients and other movement disorder cases. Secondly, we have examined in CD cases the treatment parameters that may have an effect on the T-cell responses against BoNT/A. We found that T-cell responses to BoNT/A were significantly higher in patients with CD than in those with other movement disorders. An increase in TeNT T-cell response in CD was observed when compared to un-treated controls. CD patients who were injected with BoNT/B mounted higher responses to BoNT/A than patients treated with BoNT/A only. Frequent injections (more than 2.1/year) were associated with a significantly higher T-cell response to BoNT/A in CD. T cell responses to BoNT/A did not differ between CD patients who had clinically responsive and non-responsive status at the time of enrollment. PMID- 22079195 TI - Social interaction with a rhythmic rat enhances the circadian pattern of the motor activity and temperature of LL-induced arrhythmic rats. AB - Although light is the main factor that influences circadian rhythms, social interaction may also have a role on their regulation. Here, the influence of social interaction on rat circadian behavior was investigated, addressing the question of whether cohabitation would induce the appearance of a circadian rhythm in arrhythmic rats due to constant light. To this end, circadian rhythms of motor activity and body temperature of male and female LL-induced arrhythmic rats were studied before, during and after a 20-day period in which rats stayed in the same cage with a rat of the same sex but with stronger rhythm. Results showed that the manifestation of the circadian motor activity rhythm of LL induced arrhythmic rats increased after cohabitation. In the case of the expression of the body temperature rhythm, there was a progressive daily increase in the power content of a daily 24 hour pattern throughout the cohabitation days, which remained when animals were again isolated. Thus, the presence of a rhythmic rat increases the strength of the circadian behavior of rats showing a weak circadian rhythm. PMID- 22079194 TI - 'q-Titration' of long-chain and short-chain lipids differentiates between structured and mobile residues of membrane proteins studied in bicelles by solution NMR spectroscopy. AB - 'q-Titration' refers to the systematic comparison of signal intensities in solution NMR spectra of uniformly (15)N labeled membrane proteins solubilized in micelles and isotropic bicelles as a function of the molar ratios (q) of the long chain lipids (typically DMPC) to short-chain lipids (typically DHPC). In general, as q increases, the protein resonances broaden and correspondingly have reduced intensities due to the overall slowing of protein reorientation. Since the protein backbone signals do not broaden uniformly, the differences in line widths (and intensities) enable the narrower (more intense) signals associated with mobile residues to be differentiated from the broader (less intense) signals associated with "structured" residues. For membrane proteins with between one and seven trans-membrane helices in isotropic bicelles, we have been able to find a value of q between 0.1 and 1.0 where only signals from mobile residues are observed in the spectra. The signals from the structured residues are broadened so much that they cannot be observed under standard solution NMR conditions. This q value corresponds to the ratio of DMPC:DHPC where the signals from the structured residues are "titrated out" of the spectrum. This q value is unique for each protein. In magnetically aligned bilayers (q>2.5) no signals are observed in solution NMR spectra of membrane proteins because the polypeptides are "immobilized" by their interactions with the phospholipid bilayers on the relevant NMR timescale (~10(5)Hz). No signals are observed from proteins in liposomes (only long-chain lipids) either. We show that it is feasible to obtain complementary solution NMR and solid-state NMR spectra of the same membrane protein, where signals from the mobile residues are present in the solution NMR spectra, and signals from the structured residues are present in the solid-state NMR spectra. With assigned backbone amide resonances, these data are sufficient to describe major features of the secondary structure and basic topology of the protein. Even in the absence of assignments, this information can be used to help establish optimal experimental conditions. PMID- 22079196 TI - Foxp3 is critical for human natural CD4+CD25+ regulatory T cells to suppress alloimmune response. AB - Naturally occurring CD4+CD25+ regulatory T cells (nTregs) that express high level of Foxp3 actively suppress pathological and physiological immune responses, contributing to the maintenance of immunological self-tolerance and immune homeostasis. Although Foxp3 is required for nTreg development and appears to be necessary for mature murine Treg function, the precise role of Foxp3 in regulating natural human Treg function in alloimmune response is unclear. In this study, we used siRNA-mediated gene silencing to knockdown Foxp3 expression in natural human Tregs and investigated the importance of Foxp3 in maintaining human nTreg suppressive function. We showed that Foxp3 knockdown resulted in impaired phenotype and nonresponsiveness, downregulated expression of function molecules, and reduced production of suppressive cytokines in nTregs. These changes correlated with diminished nTreg activity in suppressing proliferation of effector CD4+CD25- T cells, their cytotoxicity against allogeneic target cells and production of effector cytokines in response to allogeneic stimulation. Thus, this study shows that ongoing Foxp3 expression is required for natural human Tregs to maintain their phenotype and suppressive function in the alloimmune response. PMID- 22079197 TI - [Doctor-patient communication: one of the basic competencies, but different]. AB - Effective communication skills form part of being a good doctor. Today there is solid evidence to support the teaching of effective communication skills in all medical schools. This article describes how communication is different from the other skills that medical students and residents need to learn, how this affects teaching and learning, and the application of these ideas in a Chilean medical school. We describe the premises that need to be taken into consideration when planning teaching communication in medicine and illustrate how these affected the development of our teaching of communication in our undergraduate curriculum. All medical education programmes should include formal teaching on the doctor-patient relationship, but must take into consideration the aspects of communication teaching that make it different from teaching other aspects of medicine. PMID- 22079198 TI - Validation of the Chinese version of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form (PISQ-12). AB - OBJECTIVE: To validate the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form (PISQ-12) in a Chinese population. METHODS: The PISQ-12 was translated into Chinese; 106 women with pelvic floor disorders then completed the questionnaire and the 12-item short-form health survey (SF-12). The reliability and validity of the PISQ-12 were analyzed. RESULTS: The PISQ-12 had an adequate and high internal consistency (Cronbach alpha=0.725) and a high test retest reliability (intraclass correlation coefficient coefficient=0.745; P<0.01). Scoring of the PISQ-12 was positively correlated with that of the SF-12 (P<0.01). Factor analysis showed strong construct validity. CONCLUSION: The Chinese version of the PISQ-12 has a high reliability and validity in the Chinese population and, therefore, is highly recommended for clinical treatment and research. PMID- 22079200 TI - Active site intermediates in the reduction of O(2) by cytochrome oxidase, and their derivatives. AB - The mechanism of dioxygen activation and reduction in cell respiration, as catalysed by cytochrome c oxidase, has a long history. The work by Otto Warburg, David Keilin and Britton Chance defined the dioxygen-binding heme iron centre, viz. das Atmungsferment, or cytochrome a(3). Chance brought the field further in the mid-1970's by ingenious low-temperature studies that for the first time identified the primary enzyme-substrate (ES) Michaelis complex of cell respiration, the dioxygen adduct of heme a(3), which he termed Compound A. Further work using optical, resonance Raman, EPR, and other sophisticated spectroscopic techniques, some of which with microsecond time resolution, has brought us to the situation today, where major principles of how O(2) reduction occurs in respiration are well understood. Nonetheless, some questions have remained open, for example concerning the precise structures, catalytic roles, and spectroscopic properties of the breakdown products of Compound A that have been called P, F (for peroxy and ferryl), and O (oxidised). This nomenclature has been known to be inadequate for some time already, and an alternative will be suggested here. In addition, the multiple forms of P, F and O states have been confusing, a situation that we endeavour to help clarifying. The P and F states formed artificially by reacting cytochrome oxidase with hydrogen peroxide are especially scrutinised, and some novel interpretations will be given that may account for previously unexplained observations. PMID- 22079201 TI - Comparison of the alpha and beta isomeric forms of the detergent n-dodecyl-D maltoside for solubilizing photosynthetic complexes from pea thylakoid membranes. AB - Mild non-ionic detergents are indispensable in the isolation of intact integral membrane proteins and protein-complexes from biological membranes. Dodecylmaltoside (DM) belongs to this class of detergents being a glucoside-based surfactant with a bulky hydrophilic head group composed of two sugar rings and a non-charged alkyl glycoside chain. Two isomers of this molecule exist, differing only in the configuration of the alkyl chain around the anomeric center of the carbohydrate head group, axial in alpha-DM and equatorial in beta-DM. In this paper, we have investigated the solubilizing properties of alpha-DM and beta-DM on the isolation of photosynthetic complexes from pea thylakoids membranes maintaining their native architecture of stacked grana and stroma lamellae. Exposure of these stacked thylakoids to a single step treatment with increasing concentrations (5-100mM) of alpha-DM or beta-DM resulted in a quick partial or complete solubilization of the membranes. Regardless of the isomeric form used: 1) at the lowest DM concentrations only a partial solubilization of thylakoids was achieved, giving rise to the release of mainly small protein complexes mixed with membrane fragments enriched in PSI from stroma lamellae; 2) at concentrations above 30mM a complete solubilization occurred with the further release of high molecular weight protein complexes identified as dimeric PSII, PSI-LHCI and PSII-LHCII supercomplexes. However, at concentrations of detergent which fully solubilized the thylakoids, the alpha and beta isomeric forms of DM exerted a somewhat different solubilizing effect on the membranes: higher abundance of larger sized PSII-LHCII supercomplexes retaining a higher proportion of LHCII and lower amounts of PSI-LHCI intermediates were observed in alpha-DM treated membranes, reflecting the mildness of alpha-DM compared with its isomer. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial. PMID- 22079199 TI - Biogenesis of cbb(3)-type cytochrome c oxidase in Rhodobacter capsulatus. AB - The cbb(3)-type cytochrome c oxidases (cbb(3)-Cox) constitute the second most abundant cytochrome c oxidase (Cox) group after the mitochondrial-like aa(3)-type Cox. They are present in bacteria only, and are considered to represent a primordial innovation in the domain of Eubacteria due to their phylogenetic distribution and their similarity to nitric oxide (NO) reductases. They are crucial for the onset of many anaerobic biological processes, such as anoxygenic photosynthesis or nitrogen fixation. In addition, they are prevalent in many pathogenic bacteria, and important for colonizing low oxygen tissues. Studies related to cbb(3)-Cox provide a fascinating paradigm for the biogenesis of sophisticated oligomeric membrane proteins. Complex subunit maturation and assembly machineries, producing the c-type cytochromes and the binuclear heme b(3)-Cu(B) center, have to be coordinated precisely both temporally and spatially to yield a functional cbb(3)-Cox enzyme. In this review we summarize our current knowledge on the structure, regulation and assembly of cbb(3)-Cox, and provide a highly tentative model for cbb(3)-Cox assembly and formation of its heme b(3) Cu(B) binuclear center. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. PMID- 22079203 TI - The cytoskeletal proteins in the contractile tissues of the testis and its excurrent ducts of the passerine bird, Masked Weaver (Ploceus velatus). AB - The cellular composition of the testicular capsule, seminiferous peritubular tissue, the epithelia as well as periductal muscle cell layers of the excurrent ducts was studied, in sexually mature and active Masked Weaver (Ploceus velatus) birds of the passerine family, Ploceidae. Ultrastructure of the contractile cells in the testicular capsule, peritubular and periductal tissues showed that these cells were smooth muscles of typical morphological characteristics. Variability in the immunohistochemical co-expression of microfilaments and intermediate filaments in the different tissues was evident. Actin and desmin proteins were co expressed immunohistochemically in the testicular capsule and seminiferous peritubular smooth muscle layer. Actin was singly and very weakly expressed in the rete testis epithelium while cytokeratins and desmin were co-expressed in the epithelium of the excurrent ducts. The periductal muscle layer of all ducts of the epididymis, the ductus deferens as well as the seminal glomus, strongly co expressed actin and desmin. Vimentin was absent in all cells and tissue types studied. There is clear evidence that the tissues of the male gonad and its excurrent ducts in the Masked Weaver, as has been reported for members of the Galloanserae and Ratitae, contain well-formed contractile tissues whose function would include the transportation of luminal through-flow from the testis into, and through, its excurrent ducts. The microtubule helix in the head and of the mid-piece, of elongating spermatids, as well as of the mature spermatozoa in the various excurrent ducts, including some spermatozoa in the seminal glomus, also co-expressed these three proteins. PMID- 22079202 TI - LHON/MELAS overlap mutation in ND1 subunit of mitochondrial complex I affects ubiquinone binding as revealed by modeling in Escherichia coli NDH-1. AB - Defects in complex I due to mutations in mitochondrial DNA are associated with clinical features ranging from single organ manifestation like Leber hereditary optic neuropathy (LHON) to multiorgan disorders like mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome. Specific mutations cause overlap syndromes combining several phenotypes, but the mechanisms of their biochemical effects are largely unknown. The m.3376G>A transition leading to p.E24K substitution in ND1 with LHON/MELAS phenotype was modeled here in a homologous position (NuoH-E36K) in the Escherichia coli enzyme and it almost totally abolished complex I activity. The more conservative mutation NuoH-E36Q resulted in higher apparent K(m) for ubiquinone and diminished inhibitor sensitivity. A NuoH homolog of the m.3865A>G transition, which has been found concomitantly in the overlap syndrome patient with the m.3376G>A, had only a minor effect. Consequences of a primary LHON-mutation m.3460G>A affecting the same extramembrane loop as the m.3376G>A substitution were also studied in the E. coli model and were found to be mild. The results indicate that the overlap syndrome-associated m.3376G>A transition in MTND1 is the pathogenic mutation and m.3865A>G transition has minor, if any, effect on presentation of the disease. The kinetic effects of the NuoH-E36Q mutation suggest its proximity to the putative ubiquinone binding domain in 49kD/PSST subunits. In all, m.3376G>A perturbs ubiquinone binding, a phenomenon found in LHON, and decreases the activity of fully assembled complex I as in MELAS. PMID- 22079204 TI - Language in calculation: a core mechanism? AB - Although there is evidence that exact calculation recruits left hemisphere perisylvian language systems, recent work has shown that exact calculation can be retained despite severe damage to these networks. In this study, we sought to identify a "core" network for calculation and hence to determine the extent to which left hemisphere language areas are part of this network. We examined performance on addition and subtraction problems in two modalities: one using conventional two-digit problems that can be easily encoded into language; the other using novel shape representations. With regard to numerical problems, our results revealed increased left fronto-temporal activity in addition, and increased parietal activity in subtraction, potentially reflecting retrieval of linguistically encoded information during addition. The shape problems elicited activations of occipital, parietal and dorsal temporal regions, reflecting visual reasoning processes. A core activation common to both calculation types involved the superior parietal lobule bilaterally, right temporal sub-gyral area, and left lateralized activations in inferior parietal (BA 40), frontal (BA 6/8/32) and occipital (BA 18) regions. The large bilateral parietal activation could be attributed to visuo-spatial processing in calculation. The inferior parietal region, and particularly the left angular gyrus, was part of the core calculation network. However, given its activation in both shape and number tasks, its role is unlikely to reflect linguistic processing per se. A possibility is that it serves to integrate right hemisphere visuo-spatial and left hemisphere linguistic and executive processing in calculation. PMID- 22079205 TI - Puerarin prevents isoprenaline-induced myocardial fibrosis in mice by reduction of myocardial TGF-beta1 expression. AB - It has been reported that soy isoflavones could significantly increase peroxisome proliferator-activated receptor alpha/gamma gene expressions, while the activation of peroxisome proliferator-activated receptor alpha/gamma may attenuate myocardial fibrosis. Puerarin is the main isoflavone isolated from the root of the wild leguminous creeper Pueraria lobata (Willd) Ohwi, so we thought that puerarin could inhibit myocardial fibrotic formation. A mouse myocardial fibrotic model was induced by hypodermic injection of isoprenaline when these mice were simultaneously treated with puerarin 600 and 1200 mg/kg by gavage for 40 days, respectively. The results showed that puerarin could significantly improve myocardial fibrosis and decrease the collagen accumulation, collagen volume fraction, hydroxyproline content in myocardial tissue and cardiac weight index. The results from reverse transcription polymerase chain reaction indicated that the messenger RNA (mRNA) expression of transforming growth factor-beta1 in myocardial tissue was decreased, while the mRNA expressions of peroxisome proliferator-activated receptor alpha/gamma were increased, in the puerarin groups as compared with the model group. Importantly, puerarin could significantly decrease the protein expressions of transforming growth factor beta1 and nuclear factor-kappaB in myocardial tissue. These results suggested that puerarin could prevent isoprenaline-induced myocardial fibrosis in mice, and its mechanisms might be related to reduction of transforming growth factor-beta1 expression via activation of peroxisome proliferator-activated receptor alpha/gamma and subsequent inhibition of nuclear factor-kappaB in myocardial tissue. PMID- 22079206 TI - Molecular signature of kappa-carrageenan mimics chondroitin-4-sulfate and dermatan sulfate and enables interaction with arylsulfatase B. AB - The common food additive kappa-carrageenan (kappa-CGN) is a sulfated polysaccharide that resembles chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). All have a sulfate group on C4 of a glycoside (galactose for CGN and N acetylgalactosamine for C4S), and the sulfate-bearing glycoside is linked in a beta-1,4-configuration to an unsulfated, six-carbon sugar (galactose for CGN, glucuronate for C4S and iduronate for DS). The enzyme arylsulfatase B (ARSB; N acetylgalactosamine-4-sulfate) is the highly selective enzyme that removes the four-sulfate group from the nonreducing terminus of C4S and DS, thereby regulating subsequent degradation. In this report, kappa-CGN is shown to be a substrate for recombinant human ARSB (rhARSB). Sulfate was generated from both C4S and kappa-CGN following incubation with rhARSB. Exposure of human colonic epithelial cells to kappa-CGN, but not to C4S, produced reactive oxygen species (ROS) and increased interleukin (IL)-8 secretion. The ROS production from kappa CGN was reduced by exposure to rhARSB, but increased by competition from C4S or DS, but not from chondroitin-6-sulfate. Prior treatment of either lambda- or iota CGN with rhARSB had no impact on ROS, IL-8 or inorganic sulfate production, demonstrating a specific effect of the molecular configuration of kappa-CGN. By mimicry of C4S and DS and by interaction with ARSB, kappa-CGN can directly interfere with the normal cellular functions of C4S, DS and ARSB. Since C4S and DS are present in high concentration in tissues, the impact of kappa-CGN exposure may be due to some extent to interference with the normal biological functions of ARSB, C4S and DS. PMID- 22079207 TI - Protein restriction during gestation alters histone modifications at the glucose transporter 4 (GLUT4) promoter region and induces GLUT4 expression in skeletal muscle of female rat offspring. AB - Maternal nutrition during pregnancy is an intrauterine factor that results in alteration of the offspring genome and associates with disease risk in the offspring. We investigated the impact of a maternal low-protein (LP) diet on the expression of glucose transporter 4 (GLUT4) in offspring skeletal muscle. GLUT4 is an insulin-regulated glucose transporter involved in insulin sensitivity and carbohydrate metabolism in muscle cells. We observed sex-dependent GLUT4 mRNA expression and increased GLUT4 protein content in female pup skeletal muscle with maternal LP. Analysis of transcriptional and epigenetic regulation of increased skeletal muscle GLUT4 expression in offspring rats revealed the regulatory mechanisms involved. The protein level of myocyte enhancer factor 2A (MEF2A), which has been known as an activator of GLUT4 transcription via the ability to carry out specific binding to the GLUT4 MEF2 binding sequence, increased in female pups whose mothers were fed a LP diet. Modifications of chromatin structure, including acetylated histone H3, acetylated histone H4 and di methylated histone H3 at lysine 4, were detected at a significantly increased level at the GLUT4 promoter region in female pup muscle following a maternal LP diet. Glycogen content was also detected as up-regulated, accompanied by increased glycogen synthase in LP female offspring muscle. These results document that maternal protein restriction during pregnancy induces GLUT4 expression in female offspring skeletal muscle but not in males, which may indicate sex dependent adaptation of glucose metabolism to a maternal LP diet. PMID- 22079209 TI - Transferable cell-secreted extracellular matrices enhance osteogenic differentiation. AB - The coating of synthetic biomaterials with cell-derived decellularized extracellular matrices (DMs) represents a promising approach to confer bioactivity to otherwise inert materials and direct cell fate of host or transplanted cells. These coatings are typically deposited on biomaterials by culturing matrix-depositing cells for a sufficient duration on the target, followed by decellularization of the substrate. We hypothesized that DMs created in monolayer culture could be collected and then transferred to a secondary substrate while retaining their instructive potential. Transferred decellularized matrices (tDMs) were created by culturing human mesenchymal stem cells (hMSCs) on tissue culture plastic (TCP) under a controlled microenvironment to deposit a highly osteogenic DM, followed by collection, mechanical homogenization and transfer to a secondary culture surface. We then investigated its capacity to accelerate naive hMSC osteogenic differentiation by quantifying gene expression, intracellular alkaline phosphatase production, and calcium deposition when cultured on DMs or tDMs. All markers were significantly higher in hMSCs seeded on DMs or tDMs compared to cells on TCP. The osteogenic response of naive hMSCs to tDMs was dose dependent. We observed a reduction in ERK phosphorylation in hMSCs, as well as a possible role of the cell surface integrin alpha2beta1, when probing the mode of efficacy for tDMs. This study represents a proof-of-principle that cell-derived matrix coatings can be deposited and effectively transferred while retaining the ability to instruct cell phenotype, thus offering a novel approach toward the development of hybrid biomaterials that mimic the complex interactions between cells and the extracellular matrix. PMID- 22079208 TI - Accelerated skeletal muscle recovery after in vivo polyphenol administration. AB - Acute skeletal muscle damage results in fiber disruption, oxidative stress and inflammation. We investigated cell-specific contributions to the regeneration process after contusion-induced damage (rat gastrocnemius muscle) with or without chronic grape seed-derived proanthocyanidolic oligomer (PCO) administration. In this placebo-controlled study, male Wistar rats were subjected to PCO administration for 2 weeks, after which they were subjected to a standardised contusion injury. Supplementation was continued after injury. Immune and satellite cell responses were assessed, as well as oxygen radical absorption capacity and muscle regeneration. PCO administration resulted in a rapid satellite cell response with an earlier peak in activation (Pax7+, CD56+, at 4 h post-contusion) vs. placebo groups (PLA) (P<.001: CD56+ on Day 5 and Pax7+ on Day 7). Specific immune-cell responses in PLA followed expected time courses (neutrophil elevation on Day 1; sustained macrophage elevation from Days 3 to 5). PCO dramatically decreased neutrophil elevation to nonsignificant, while macrophage responses were normal in extent, but significantly earlier (peak between Days 1 and 3) and completely resolved by Day 5. Anti-inflammatory cytokine, IL-10, increased significantly only in PCO (Day 3). Muscle fiber regeneration (MHC(f) content and central nuclei) started earlier and was complete by Day 14 in PCO, but not in PLA. Thus, responses by three crucial cell types involved in muscle recovery were affected by in vivo administration of a specific purified polyphenol in magnitude (neutrophil), time course (macrophages), or time course and activation state (satellite cell), explaining faster effective regeneration in the presence of proanthocyanidolic oligomers. PMID- 22079210 TI - Ensemble fits of restrained peptides' conformational equilibria to NMR data. Dependence on force fields: AMBER/8 ff03 versus ECEPP/3. AB - Two variants of NMR-based conformational analyses of flexible peptides are compared using two examples meeting the formula Tyr-D-Daa-Phe-Daa-NH2 (Daa=diamino acid): 1 combining D-Dab2 (alpha,gamma-diaminobutyryl) with Lys4, and 2 -D-Dap2 (alpha,beta-diaminopropionyl) with Orn4. The omega-amino groups of D-Daa2 and Daa4 are coupled with C=O into the urea, restraining 1 and 2 with 16- and 14-membered rings and leading to potent and impotent MU/delta opioid peptides, respectively. To the current task, we took from an earlier work (Filip et al, J. Pept. Sci. 11 (2005) 347-352) the NMR NOE- and J-data in H2O/D2O; and the selection of the ensembles of 1 and 2, 822 and 788 conformational families, respectively, obtained by using the EDMC/ECEPP3 method. Here, we generated ensembles of 1 and 2 using AMBER molecular dynamics in explicit water to eventually selected 686 and 761 conformers for 1 and 2, respectively. We did numbers of fits for both types of the conformational ensembles of 1 and 2 to their NOE- and J-data using a common method i.e. maximum entropy approach (Groth et al, J. Biomol. NMR 15 (1999) 315-330). Both types of the well structurally diversified ensembles fit to quite different equilibria in regressions to common experimental NOE- and J-restraints using maximum entropy principle, which is a disappointing message. Intriguing is startlingly small standard deviation in J couplings: sigma(JNHalphaH) ~ 0.01 Hz for LES-MD/AMBER ensemble, contrary to sigma(JNHalphaH) = 0.8 - 1.1 Hz for the EDMC/ECEPP ensemble, over the wide range of entropy, i.e. relatively insensitive to it. A similar feature is not the case when comparing sigma(NOE) in both methods. Hence, at minute entropy contributions, it follows that J does or does not transpose "overfitted" into the final sigma(J) in the AMBER or ECEPP ensemble, respectively. Could this be an effect of softness of the AMBER flexible-valence force field compared to ECEPP rigid-geometry, and its effect on ensemble sampling? We do not know an answer. PMID- 22079211 TI - The importance of patient-centered care for various patient groups. AB - OBJECTIVES: To assess differences in the importance ascribed to patient-centered care between various patient groups and demographic groups. METHODS: Survey data collected using questionnaires were analyzed for patients that underwent hip or knee surgery (n=214), patients suffering from rheumatoid arthritis (n=343), spinal disk herniation (n=145), breast abnormalities (n=596) or congestive heart failure (n=118). A composite for patient-centered care priorities was constructed (alpha=0.82) and compared to the average importance over all healthcare aspects in the surveys. RESULTS: All patient groups considered patient-centered care to be of above-average importance (p's<0.001). Small but significant differences were observed: patient-centered care was more important for patients suffering from congestive heart failure (p<0.001) and patients who were younger, female, well-educated and healthier (p's<0.05). Patients who had undergone hip or knee surgery considered patient-centered care more important than patients with spinal disk herniation did (p<0.05). CONCLUSION: Patient-centered care is important to all patient groups. Differential policies regarding patient-centered care for patient subgroups do not seem required. PRACTICAL IMPLICATIONS: Given the importance attributed to patient-centered care, it is essential that elements of patient-centered care are included in surveys, indicators of quality of care, and the training of doctors and nurses. PMID- 22079212 TI - Random inducible controlled expression (RICE) for identification of mycobacterial virulence genes. AB - We have developed Random Inducible Controlled Expression (RICE), a high throughput genetic approach to identify regulated virulence pathways in pathogenic mycobacteria. RICE allows expression of bacterial genes under conditions where they are normally off, e.g. under laboratory growth conditions, via the use of an inducible or constitutive promoter as well as gene dosage effects due to the presence of the gene on a plasmid. Mycobacterial genomic DNA can be digested to yield random fragments for cloning into a suicide expression vector downstream of a mycobacterial promoter or with their own promoter on a replicating plasmid increasing expression by gene dosage effects. The plasmid DNA is normally amplified in Escherichia coli and delivered into mycobacteria to select for recombinants or plasmid transformants. The resulting library is then directly screened for enhanced host cell interactions in functional assays that evaluate the efficiency of adherence, entry and replication inside host cells. This approach has resulted in identification of several virulence factors from pathogenic mycobacteria. Our analysis of one such locus identified by RICE, the mycobacterial enhanced entry locus (mel2), found that the genes present facilitate bacterial persistence inside the host by protecting the pathogen against oxidative damage. Thus, we have developed a genetic strategy that offers several advantages: (i) it allows identification of bacterial genetic elements that have a direct role during host-pathogen interactions (ii) it can be used to identify virulence factors in a broad range of pathogens and (iii) it can reveal genes that are only induced at specific stages of infection. PMID- 22079213 TI - Pleiotropic cellular, hemostatic, and biological actions of Ankaferd hemostat. AB - Sustaining hemostasis in clinical hemorrhages is a challenging task and requires extensive effort to stabilize medically hard-to-treat traumatic injuries. Several hemostatic agents are preferred to control external and internal bleedings, yet commercially available products are not sufficiently effective or fast-acting to achieve hemostasis in extreme cases. Ankaferd Blood Stopper (ABS) is a herbal extract traditionally used as a hemostatic agent. Recent studies have shown that ABS could be utilized successfully as a hemostatic agent for the management of clinical hemorrhages when conventional methods were ineffective. This review serves as a basis to provide recent findings on several applications of ABS, specifically preclinical, biological, and clinical studies both in vitro and in vivo. Another section focuses on the ultrastructural morphology and protein network formation of ABS in an effort to understand the hemostatic mechanisms of this unique agent at tissue level. PMID- 22079214 TI - Assessing the latent structure of the intolerance of uncertainty construct: an initial taxometric analysis. AB - Researchers have increasingly suggested that people with anxiety disorders share a common fear that the uncertain future will be catastrophic. Intolerance of uncertainty (IU) - the tendency to consider possible negative events as unacceptable and threatening, irrespective of probabilities - is representative of such fears. A key role has been indicated for IU in several anxiety and mood disorders; however, the present study appears to be the first latent structure examination of IU. Responses were obtained from a large sample (n=977; 65% women) unselected with regard to IU level, comprising anxiety disorder outpatients (i.e., putative taxon members), and community residents (i.e., putative complement class members). MAXEIG, MAMBAC, and L-Mode were performed with indicator sets drawn from the Intolerance of Uncertainty Scale-12. Assessments also included objective Comparison Curve Fit Indices. Results yielded converging evidence that IU symptoms have a dimensional latent structure. Comprehensive findings, implications, and future research directions are discussed. PMID- 22079215 TI - Changes in risk-taking over the course of an internet-delivered cognitive behavioral therapy treatment for generalized anxiety disorder. AB - It has been proposed that a persistent and pervasive tendency to avoid risks is involved in the development and maintenance of clinically significant anxiety. Few studies, however, have examined the clinical implications of risk-aversion, and particularly the association between risk-aversion and treatment outcome. The current study investigated how risk-aversion in specific domains (Social and Recreational) related to treatment outcome in a clinical sample of patients with generalized anxiety disorder (GAD) undergoing internet-delivered cognitive behavioral therapy (CBT). We hypothesized that: (i) risk-taking would increase as a result of treatment and (ii) risk-taking would mediate changes in symptom severity and impairment as a result of treatment. Individuals recruited online (N=44) meeting diagnostic criteria for GAD were randomized to the treatment (n=24) or control group (n=20). Participants completed measures of symptom severity, impairment and risk-taking before and after treatment. Results partially confirmed our hypotheses, demonstrating that participants in the treatment group significantly increased social and recreational risk-taking scores relative to the control group and risk-taking mediated treatment outcome for depression, but not for anxiety symptoms. The results of this study suggest that social and recreational risk-avoidance decreases following CBT treatment, and this change may mediate treatment outcome for depression. Clinical implications of these findings are discussed. PMID- 22079217 TI - The germfree murine animal: an important animal model for research on the relationship between gut microbiota and the host. AB - Scientific findings in recent decades have demonstrated that the commensal intestinal microbiota has profound effects on the physiology and diseases of the host. It is estimated that the human microbiota is composed of 10(14) bacterial cells, a number 10 times greater than the total number of human cells. The variety and the complex interactions of the intestinal microbiota are associated with physiological details that remain largely unknown. Germfree hosts, especially murine (rat or mouse) animals that have been maintained free from demonstrable microbial associates such as bacteria, viruses, fungi, and parasites throughout life, have become a powerful tool for exploring the interplay between the host and microorganisms inhabiting the human intestine. This review and survey of recent findings will argue that the germfree mouse model can produce its greatest potential benefits in the study of the metabolism and immunity of the host. PMID- 22079216 TI - Diversity and zoonotic potential of rotaviruses in swine and cattle across Europe. AB - Group A rotaviruses can infect both humans and animals. Individual rotavirus strains can occasionally cross species barriers and might hereby contribute to the emergence of new genotypes in heterologous hosts. The incidence and impact of zoonotic rotavirus are not well defined, and one reason for this is a lack of data about strains circulating in suspected reservoir animal hosts. In this study we report the incidence, genetic diversity, and molecular epidemiology of rotaviruses detected in domestic cattle and swine in 6 European countries. From 2003 to 2007, 1101 and more than 2000 faecal specimens were collected from swine and cattle, both healthy and diarrhoeic, and tested for rotaviruses. Viruses from positive stools were genotyped and a subset of strains was characterized by nucleotide sequencing and phylogenetic analysis of the VP7 (G) and VP4 (P) genes. Rotaviruses were detected in 43% of bovine samples and in 14% of porcine samples. In cattle, 10 different combinations of G and P types were identified and the most common strains were G6P[11] and G6P[5]. In swine, the number of identified G P combinations was higher (n=21), however, no single combination was predominant across Europe. Newly described genotype specificities, P[27] and P[32], were identified in swine. When compared at the nucleotide sequence level, the identified porcine rotavirus strains and contemporary human strains grouped together phylogenetically, whereas bovine rotavirus strains formed separate clades. These data demonstrate large genetic diversity of porcine and bovine rotavirus strains across Europe, and suggest that livestock herds may serve as potential reservoirs for human infections. PMID- 22079218 TI - Detection of avian rotaviruses of groups A, D, F and G in diseased chickens and turkeys from Europe and Bangladesh. AB - Avian rotaviruses (AvRVs) represent a diverse group of intestinal viruses, which are suspected as the cause of several diseases in poultry with symptoms of diarrhoea, growth retardation or runting and stunting syndrome (RSS). To assess the distribution of AvRVs in chickens and turkeys, we have developed specific PCR protocols. These protocols were applied in two field studies investigating faecal samples or intestinal contents of diseased birds derived from several European countries and Bangladesh. In the first study, samples of 166 chickens and 33 turkeys collected between 2005 and 2008 were tested by PAGE and conventional RT PCR and AvRVs were detected in 46.2%. In detail, 16.1% and 39.2% were positive for AvRVs of groups A or D, respectively. 11.1% of the samples contained both of them and only four samples (2.0%) contained rotaviruses showing a PAGE pattern typical for groups F and G. In the second study, samples from 375 chickens and 18 turkeys collected between 2009 and 2010 were analyzed using a more sensitive group A-specific and a new group D-specific real-time RT-PCR. In this survey, 85.0% were AvRV-positive, 58.8% for group A AvRVs, 65.9% for group D AvRVs and 38.9% for both of them. Although geographical differences exist, the results generally indicate a very high prevalence of group A and D rotaviruses in chicken and turkey flocks with cases of diarrhoea, growth retardation or RSS. The newly developed diagnostic tools will help to investigate the epidemiology and clinical significance of AvRV infections in poultry. PMID- 22079219 TI - Isolated exercise-induced rhabdomyolysis of brachialis and brachioradialis muscles: an atypical clinical case. AB - OBJECTIVE AND PATIENT: To report an atypical case of exercise-induced bilateral brachialis and brachioradialis rhabdomyolysis in a 25-year-old woman. DISCUSSION AND CONCLUSION: Persistent focal muscle pain, atypical by its duration and intensity, even after moderate exercise, should prompt the search for rhabdomyolysis and discuss the possibility of acute compartment syndrome. MRI images can validate the muscle edema. Progressive and adapted training as well as respecting individual limits are necessary measures to prevent rhabdomyolysis. PMID- 22079220 TI - Pc16a, the first characterized peptide from Conus pictus venom, shows a novel disulfide connectivity. AB - A novel conotoxin, pc16a, was isolated from the venom of Conus pictus. This is the first peptide characterized from this South-African cone snail and it has only 11 amino acid residues, SCSCKRNFLCC*, with the rare cysteine framework XVI and a monoisotopic mass of 1257.6Da. Two peptides were synthesized with two possible conformations: globular (pc16a_1) and ribbon (pc16a_2). pc16a_1 co eluted with the native peptide, which indicates a disulfide connectivity I-III, II-IV. The structure of pc16a_1 was determined by NMR. Both synthetic peptides were used to elucidate the biological activity. Bioassays were performed on crickets, ghost shrimps, larvae of the mealworm beetle and mice, but no effect was seen. Using two-electrode voltage clamp, a range of voltage-gated ion channels (Na(v) and K(v)) and nicotinic acetylcholine receptors were screened, but again no activity was found. Hence, the specific target of pc16a still remains to be discovered. PMID- 22079221 TI - The cardioprotective effect of different doses of vasopressin (AVP) against ischemia-reperfusion injuries in the anesthetized rat heart. AB - The aim of the present study was to investigate the protective effect of various doses of exogenous vasopressin (AVP) against ischemia-reperfusion injury in anesthetized rat heart. Anesthetized rats were randomly divided into seven groups (n=4-13) and all of them subjected to prolonged 30 min regional ischemia and 120 min reperfusion. Group I served as saline control with ischemia, in treatment groups II, III, IV and V, respectively different doses of AVP (0.015, 0.03, 0.06 and 1.2 MUg/rat) were infused within 10 min prior to ischemia, in group VI, an AVP-selective V1 receptor antagonist (SR49059, 1mg/kg, i.v.) was administrated prior to effective dose of AVP injection and in group VII, SR49059 (1 mg/kg, i.v.) was only administrated prior to ischemia. Various doses of AVP significantly prevented the decrease in heart rate (HR) at the end of reperfusion compared to their baseline and decreased infarct size, biochemical parameters [LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB) and MDA (malondialdehyde) plasma levels], severity and incidence of ventricular arrhythmia, episodes and duration of ventricular tachycardia (VT) as compared to control group. Blockade of V1 receptors by SR49059 attenuated the cardioprotective effect of AVP on ventricular arrhythmias and biochemical parameters, but partially returned infarct size to control. AVP 0.03 MUg/rat was known as effective dose. Our results showed that AVP owns a cardioprotective effect probably via V1 receptors on cardiac myocyte against ischemia/reperfusion injury in rat heart in vivo. PMID- 22079222 TI - Investigation of the potential involvement of eicosanoid metabolites in anti diuretic hormone signaling in Rhodnius prolixus. AB - The use of naturally occurring plant-derived compounds for controlling insect pests remains an attractive alternative to potentially dangerous synthetic chemical compounds. One prospective plant-based compound, isoforms of the so called jack bean urease (JBU) from the jack bean, Canavalia ensiformis, as well a derived peptide, Jaburetox-2Ec, have insecticidal effects on an array of insect species. In the Chagas' disease vector, Rhodnius prolixus, some of the physiological effects attributed to these urease isoforms include inhibition of serotonin (5-HT)-stimulated fluid secretion by the Malpighian tubules (MTs). Here, we investigated whether the effects of these exogenous urease isoforms were targeting the neuroendocrine network involved in the anti-diuretic hormone (RhoprCAPA-2) signaling cascade. We show that pharmacological agents known to interfere with eicosanoid metabolite biosynthesis do not affect RhoprCAPA-2 inhibition of 5-HT-stimulated fluid secretion by MTs. In addition, we demonstrate that RhoprCAPA-2 inhibition of MTs is independent of extracellular or intracellular calcium. Using a heterologous system for analysis of receptor activation, we show that neither JBU nor Jaburetox-2Ec are agonists of the anti diuretic hormone receptor, RhoprCAPAr1. Finally, activation of the receptor using sub-maximal doses of the natural ligand, RhoprCAPA-2, was not influenced by the presence of either JBU or Jaburetox-2Ec indicating that the urease isoforms do not compete with RhoprCAPA-2 for binding and activation of RhoprCAPAr1. Taken together, these results suggest that at least two distinct mechanisms leading to inhibition of fluid secretion by MTs exist in R. prolixus and, unlike the urease related effects, the eicosanoid metabolite pathway is not involved in RhoprCAPA-2 mediated anti-diuresis. PMID- 22079223 TI - Estradiol-activated estrogen receptor alpha does not regulate mature microRNAs in T47D breast cancer cells. AB - Breast cancers are sensitive to hormones such as estrogen, which binds to and activates estrogen receptors (ER) leading to significant changes in gene expression. microRNAs (miRNA) have emerged as a major player in gene regulation, thus identification of miRNAs associated with normal or disrupted estrogen signaling is critical to enhancing our understanding of the diagnosis and prognosis of breast cancer. We have previously shown that 17beta-estradiol (E2) induced activation of ERalpha in T47D cells results in significant changes in the expression of protein-coding genes involved in cell cycle, proliferation, and apoptosis. To identify miRNAs regulated by E2-activated ERalpha, we analysed their expression in T47D cells following E2-activation using both dual-color microarrays and TaqMan Low Density Arrays, and validations were carried out by real-time PCR. Although estrogen treatment results in altered expression of up to 900 protein-coding transcripts, no significant changes in mature miRNA expression levels could be confirmed. Whereas previous studies aiming to elucidate the role of miRNA in ER-positive breast cancers cell lines have yielded conflicting results, the work presented here represents a thorough investigation of and significant step forward in our understanding of ERalpha mediated miRNA regulation. PMID- 22079224 TI - [Visceral leishmaniasis in two patients treated with methotrexate for rheumatoid arthritis]. PMID- 22079225 TI - [Serological profile of immigrant pregnant women against HIV, HBV, HCV, rubella, Toxoplasma gondii, Treponema pallidum, and Trypanosoma cruzi]. AB - INTRODUCTION: The increase in immigration is changing the prevalence of mother to child infectious diseases. Our aim is to determine the serological profile of foreign pregnant women against these infections. METHODS: A retrospective cross sectional study was performed in a tertiary hospital from Madrid between August 2007 and October 2008. The seroprevalence against HIV, HBV, HCV, rubeola, T. gondii, T. pallidum and T. cruzi was determined in every pregnant immigrant, as well as in a representative group of Spanish pregnant women. RESULTS: A total of 2526 immigrant and 157 Spanish pregnant women were studied. None of the Spanish and 0.5% of the foreigners showed antibodies against HIV; 18.9% of them were Sub Saharan women. Antigen HBs was detected in 2% of the immigrant women and in 1.1% of the Spanish women. Asian women had the highest rate of type B Hepatitis (10.9%). There was 0.9% of type C Hepatitis among the immigrants and 1% among the Spanish. Within the cases with RPR >= 1/8, 1.6% were immigrants, most of whom were Latin American. Thirty-one per cent of the immigrants showed antibodies against T. gondii (37.5% from Central America, 2.5% from the Far East). More than 95% of the Spanish women had antibodies against Rubella, this being lower in the rest of the areas (75.5% in Sub-Saharan Africa). T. cruzi infection was detected in 12.1% of the Bolivian women studied. CONCLUSION: The prevalence of mother-to child transmitted infections depends on the origin of pregnant women. Knowledge of these differences may lead to improved control these diseases. PMID- 22079226 TI - [Severe pneumonia in a patient infected with human immunodeficiency virus (HIV)]. PMID- 22079227 TI - [Taxonomy and biology of fungi causing human infection]. AB - The advent of molecular techniques, mainly DNA sequencing, has led to important changes in the taxonomy of pathogenic fungi and a better understanding of the phylogenetic relationships among them. The number of fungal species potentially pathogenic for humans has increased dramatically. Most of them are cryptic species belonging to complex species that have replaced traditional single morphospecies. This has occurred in several genera of mucorales and particularly in different ascomycetous genera, such as Aspergillus, Fusarium, Sporothrix and Scedosporium, among others. The correct identification of these species is crucial for a better management of patients, since on many occasions those species show different virulence and different antifungal responses. This review summarises some of the most striking recent taxonomic changes produced in pathogenic fungi. PMID- 22079228 TI - [Relapses of leishmaniasis in an HIV infected patient: a therapeutic challenge]. PMID- 22079229 TI - [Memories of AIDS: lost opportunities]. PMID- 22079230 TI - [Does the cost of the drugs influence the choice of antiretroviral treatment regimens?]. PMID- 22079231 TI - [Skin lesions and fever in an VIH-infected patient]. PMID- 22079232 TI - [General epidemiology of invasive fungal disease]. AB - Invasive mycoses associated with high morbidity and mortality rates are increasing among immunocompromised or severely ill patients. Candida, Cryptococcus, Pneumocystis and Aspergillus are most prevalent agents with varying distribution as regards geography, patient condition and hospital units. The latest multicentre candidaemia survey conducted in Spain, showed C. albicans as the most frequently isolated species followed by C. parapsilosis, C. glabrata, C. tropicalis and C. krusei in contrast with other European or American studies where C. glabrata was second in rank. Aspergillus spp. is the leading agent causing invasive mycoses among filamentous fungi followed by Fusarium spp., Scedosporium spp. and zygomycetes. Aspergillus fumigatus is the most common agent in invasive aspergillosis (and azole-resistant isolates have been reported) but in the last few years Aspergillus flavus, Aspergillus nidulans and Aspergillus terreus have been isolated with increasing frequency variable with geographical factors, patients' underlying conditions or previous antifungal treatments. PMID- 22079233 TI - Somatic mtDNA mutations in lung tissues of pesticide-exposed fruit growers. AB - Some pesticides have been considered potential chemical mutagens and their widespread use involves the assessment of their potentially hazardous effects. The mitochondrial genome is especially prone to DNA damage and thus can serve as a biomarker to monitor the genotoxicity of pesticides to human DNA. We performed a screening for somatic mutations in lung tissues from pesticide-exposed fruit growers, by direct comparing the entire mtDNA sequences of the lung tissue and the matched peripheral blood from the same individual. A phylogenetic approach and a high standard procedure were utilized to avoid potential errors in data generation and analysis. We observed a significantly increased frequency of mtDNA somatic mutations in lung tissues which had been exposed to pesticides multiple times by inhalation, and the potential biological significance of these mutations was further discussed. The samples represented in this observational study, which has multiple exposures to pesticides, experience a significant greater incidence of mtDNA mutations, suggesting that multiple exposures to pesticides could damage human mtDNA and cause somatic mutations. PMID- 22079234 TI - Mechanisms in cancer-chemotherapeutic drugs-induced peripheral neuropathy. AB - Anti-cancer drugs such as vincristine, paclitaxel, oxaliplatin, cisplatin and bortezomib are well reported to exert direct and indirect effects on sensory nerves to alter the amplitude of action potential, conduction velocity and induce pain. It results in patient suffering and also limits the treatment with potentially useful anticancer drugs. The different scientists have worked in this area to explore the mechanisms responsible for its pathogenesis. Anti-cancer agents activate plasma membrane localized ion channels on dorsal root ganglia and dorsal horn neurons including sodium, calcium, potassium, glutamate activated NMDA receptors to alter cytosolic ionic mileu particularly intracellular calcium that trigger secondary changes to induce neuropathic pain. These may include opening of mPTP pore on mitochondria to induce intracellular calcium release; activation of protein kinase C; phosphorylation of TRPV; activation of calpases/calpains; generation of nitric oxide and free radicals to induce cytotoxicity to axons and neuronal cell bodies. Furthermore, the inflammatory process initiated in glial cells and macrophages also trigger changes in the sensory neurons to alter nociceptive processing. The present review elaborates the role of all these individual targets in the pathogenesis of anticancer agents induced neuropathic pain to develop effective therapeutic modalities for pain management. PMID- 22079235 TI - Gene expression and epigenetic changes by furan in rat liver. AB - Furan, a widely used industrial compound, has been found in a number of heated food items. Furan is carcinogenic to rats and mice, but the mechanism behind its carcinogenic effect is still not well understood. In this study, we tested the hypothesis that alteration of gene expression relating to cell cycle, apoptosis, DNA damage and of epigenetic modifications including miRNA and DNA methylation may contribute to rodent carcinogenicity of furan. Using quantitative PCR arrays specific to cell cycle-, apoptosis- and DNA damage-related genes, we found that three months furan treatment at 30 mg/kg (5 daily doses per week) induced extensive mRNA expression changes (largely up-regulation) in male Sprague Dawley rat liver, and the gene expression changes did not fully recover after a one month withdrawal of furan. We also found 18 miRNAs were up-regulated and 12 were down-regulated by PCR arrays. Many of these deregulated miRNAs were also found to have similar changes in furan-induced tumour samples. Both hyper- and hypo methylation of specific gene promoter regions were identified and validated in the 3-month samples and tumour samples by microarray and COBRA (combined bisulfite restriction analysis). No global DNA methylation change was found in the 3 month treatment groups by LC-MS/MS, while furan-induced tumour samples showed global hypomethylation compared to non-tumour tissues. In conclusion, three months furan treatment at a carcinogenic dose resulted in irreversible gene expression changes, miRNA modulation and DNA methylation alteration in combination with a DNA-damage response, which suggests that non-genotoxic mechanisms are important for furan carcinogenicity. PMID- 22079236 TI - Emerging dysfunctions consequent to combined monoaminergic depletions in Parkinsonism. AB - The loss of dopamine (DA) neurons has been the pathophysiological focus of the devastating conditions of Parkinson's disease, but depletion of DA alone in animal models has failed to simultaneously elicit both the motor and non-motor deficits of PD. The present study aimed to investigate, in rats, the respective role of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) depletions on motor and non-motor behaviors and on subthalamic (STN) neuronal activity. We show that NA or DA depletion significantly decreased locomotor activity and enhanced the proportion of bursty and irregular STN neurons. Anxiety-like states required DA depletion plus the depletion of 5-HT or NA. Anhedonia and "depressive-like" behavior emerged only from the combined depletion of all three monoamines, an effect paralleled by an increase in the firing rate and the proportion of bursty and irregular STN neurons. Here, we provide evidence for the exacerbation of behavioral deficits when NA and/or 5-HT depletions are combined with DA depletion, bringing new insight into the combined roles of the three monoamines in PD. PMID- 22079238 TI - Complete mitochondrial genomes of Diplogonoporus balaenopterae and Diplogonoporus grandis (Cestoda: Diphyllobothriidae) and clarification of their taxonomic relationships. AB - Although the diplogonadic human tapeworm, Diplogonoporus grandis, has long been considered to be a synonym of the whale tapeworm, Diplogonoporus balaenopterae, the identity of the both species at the complete mitochondrial genomes and nuclear DNA levels has been not sufficiently undertaken to date. In the present study, to clarify the taxonomic relationships between D. balaenopterae and D. grandis at the molecular level, the complete mitochondrial genomes of both species were sequenced and compared. In addition, the genetic variation in the mitochondrial cytochrome c oxidase subunit 1 gene (cox1) and the nuclear internal transcribed spacer-1 (ITS-1) region of the ribosomal RNA gene were examined. The complete mitochondrial genomes of D. balaenopterae and D. grandis consisted of 13,724 bp and 13,725 bp, respectively. These mitochondrial genomes contained 12 protein-coding, 22 transfer RNA and 2 ribosomal RNA genes and two longer non coding regions. Except for Hymenolepis diminuta, the genomic organization in both species was essentially identical to that in other cestode genomes examined to date. However, differences were observed between Diplogonoporus and Diphyllobothrium species in abbreviated stop codons, sequences and the number of repeat units in the 2nd non-coding regions. The genetic differences observed in the mitochondrial genomes, cox1 and ITS-1 regions of both species were considered typical of intraspecific variation. In conclusion, D. balaenopterae is a taxonomically valid species and D. grandis is a junior synonym of D. balaenopterae based on the zoological nomenclature. Further, molecular phylogenetic analysis confirmed that D. balaenopterae is more closely related to Diphyllobothrium stemmacephalum, the type-species of the genus Diphyllobothrium, and the taxonomical validity of the genera Diplogonoporus and Diphyllobothrium was also discussed. PMID- 22079239 TI - Central auditory nervous system dysfunction in infants with non-syndromic cleft lip and/or palate. AB - OBJECTIVE: Peripheral hearing loss has been commonly reported in children with non-syndromic cleft lip and/or palate (NSCLP) but few studies have provided information about central auditory nervous system (CANS) functioning for this group. The main objective of this study was to explore CANS functioning in infants with NSCLP through analysis of auditory evoked potentials (AEPs). METHODS: AEPs including auditory brainstem response (ABR), middle latency response (MLR), and mismatch negativity (MMN) recordings were conducted in 34 infants of Chinese ethnicity with NSCLP and an equivalent number of normal controls. RESULTS: There was no significant difference in ABR (all measurements, including wave I, III, V latencies, I-V inter-wave latency, and wave V amplitude), or MLR (recordable components, Na, Pa latencies, and Na-Pa amplitude) findings between the two groups. However, infants with NSCLP had a significantly smaller MMN response than their normal controls, using MMN strength as the measurement. CONCLUSIONS: Significant abnormal auditory evoked potential findings at the cortical level suggest that infants with NSCLP may be at risk of central auditory discrimination dysfunction. Further effort is needed to determine auditory processing abilities in infants with NSCLP. PMID- 22079237 TI - Microarray analysis of CA1 pyramidal neurons in a mouse model of tauopathy reveals progressive synaptic dysfunction. AB - The hTau mouse model of tauopathy was utilized to assess gene expression changes in vulnerable hippocampal CA1 neurons. CA1 pyramidal neurons were microaspirated via laser capture microdissection followed by RNA amplification in combination with custom-designed microarray analysis and qPCR validation in hTau mice and nontransgenic (ntg) littermates aged 11-14months. Statistical analysis revealed ~8% of all the genes on the array platform were dysregulated, with notable downregulation of several synaptic-related markers including synaptophysin (Syp), synaptojanin, and synaptobrevin, among others. Downregulation was also observed for select glutamate receptors (GluRs), Psd-95, TrkB, and several protein phosphatase subunits. In contrast, upregulation of tau isoforms and a calpain subunit were found. Microarray assessment of synaptic-related markers in a separate cohort of hTau mice at 7-8months of age indicated only a few alterations compared to the 11-14month cohort, suggesting progressive synaptic dysfunction occurs as tau accumulates in CA1 pyramidal neurons. An assessment of SYP and PSD 95 expression was performed in the hippocampal CA1 sector of hTau and ntg mice via confocal laser scanning microscopy along with hippocampal immunoblot analysis for protein-based validation of selected microarray observations. Results indicate significant decreases in SYP-immunoreactive and PSD-95-immunoreactive puncta as well as downregulation of SYP-immunoreactive and PSD-95-immunoreactive band intensity in hTau mice compared to age-matched ntg littermates. In summary, the high prevalence of downregulation of synaptic-related genes indicates that the moderately aged hTau mouse may be a model of tau-induced synaptodegeneration, and has profound effects on how we perceive progressive tau pathology affecting synaptic transmission in AD. PMID- 22079240 TI - Internet skill-related problems in accessing online health information. AB - PURPOSE: Despite the amount of health information available online, there are several barriers that limit the Internet from being adopted as a source of health information. The purpose of this study was to identify individual skill-related problems that users experience when accessing the Internet for health information and services. METHODS: Between November 2009 and February 2010, 88 subjects participated in a performance test in which participants had to complete health related assignments on the Internet. Subjects were randomly selected from a telephone book. A selective quota sample was used and was divided over equal subsamples of gender, age, and education. Each subject was required to complete nine assignments on the Internet. RESULTS: The general population experiences many Internet skill-related problems, especially those related to information and strategic Internet skills. Aging and lower levels of education seemed to contribute to the amount of operational and formal skill-related problems experienced. Saving files, bookmarking websites, and using search engines were troublesome for these groups of people. With respect to information skills, the higher the level of educational attainment, the less problems the participants experienced. Although younger subjects experienced far less operational and formal skill-related problems, it was revealed that older subjects were less likely to select and use irrelevant search results and unreliable sources. Concerning the strategic Internet skills it was revealed that older subjects were less likely to make inappropriate decisions based on information gathered. CONCLUSIONS: The amount of online health-related information and services is consistently growing; however, it appears that the general population experiences many skill-related problems, particularly those related to information and strategic Internet skills, and they become very important when it comes to health. These skills are also problematic for younger generations who are often seen as skilled Internet users. The results of the study call for policies that account for low levels of Internet skills. PMID- 22079241 TI - Chronic conditions (such as heart disease and stroke). PMID- 22079242 TI - Development and evaluation of data entry templates based on the entity-attribute value model for clinical decision support of pressure ulcer wound management. AB - PURPOSES: The purpose of this study was to develop and evaluate the functionality of structured data entry templates using the entity-attribute-value (EAV) model for clinical decision support of pressure ulcer wound management. METHODS: A data set for wound assessment of pressure ulcers that has commonly been recommended by clinical practice guidelines was identified, and then the EAV models on each data were developed. Structured data entry templates and a database were developed based on these EAV models. These were integrated with a knowledge engine into the clinical decision support system (CDSS) to provide patient-specific recommendations on pressure ulcer wound management. The functionality of the EAV model and structured data entry templates for the CDSS was evaluated heuristically by five nurse experts using clinical scenarios. RESULTS: The data set containing 13 entities was identified and EAV models of these entities were created. Cardinalities and data types of attributes were defined to represent the models in more detail. Terms used in the EAV models were mapped to SNOMED CT concepts. Six data entry templates and the relational database with ten tables were developed. Five nurses successfully entered all data in the scenarios except one data element and retrieved expected recommendations successfully from the clinical decision support system when all data were entered correctly. CONCLUSIONS: The clinical data models and structured data entry templates developed in this study were useful in supporting clinical decision making on pressure ulcer wound management. PMID- 22079243 TI - Regulation of human CYP11B1 and CYP11B2 promoters by transposable elements and conserved cis elements. AB - CYP11B1 and CYP11B2 responsible for the final steps of cortisol and aldosterone synthesis, respectively, are believed to be duplicate genes with distinctive promoters. Our sequence analysis uncovers that these two genes share great homology in the proximal upstream regions, but insertion of Alu and L1 elements drives promoters divergent. Each CYP11B promoter contains two Alu elements embedded in a truncated L1 element, breaking L1 into three disconnected fragments. Alu functions as an enhancer in both genes regardless of orientation and copy number. Insertion of Alu upstream of a SV40 promoter also elevates promoter activity. However, the effect of Alu on CYP11B1 is blocked by a second L1 element (CYP11B1-L1.2) inserted between the first one and the conserved proximal upstream region. Although CYP11B1-L1.2 is 5'-truncated and lacks a functional ORF, replacing it with a fluorescent gene demonstrates that the element can be transcribed from the CYP11B1 core promoter in an opposite direction and a smaller magnitude compared to CYP11B1. Deletion of CYP11B1-L1.2 greatly increases CYP11B1 promoter activity and restores the enhancing effect of Alu. The Ad5 and SF-1 binding elements conserved in the proximal core promoter play a role in basal expression of both genes. Mutation of the Ad5 site reduces promoter activity to the minimal level. ERRalpha is the transcription factor interacting with Ad5 during basal expression. The core promoters of both genes are also conserved in mouse and rat despite the fact that the sites corresponding to cre, Ad5, and SF-1 in rodent Cyp11b1 promoters deviate from consensus. PMID- 22079244 TI - Recent and potential developments of biofluid analyses in metabolomics. AB - Metabolomics, one of the 'omic' sciences in systems biology, is the global assessment and validation of endogenous small-molecule metabolites within a biologic system. Analysis of these key metabolites in body fluids has become an important role to monitor the state of biological organisms and is a widely used diagnostic tool for disease. A majority of these metabolites are being applied to metabolic profiling of the biological samples, for example, plasma and whole blood, serum, urine, saliva, cerebrospinal fluid, synovial fluid, semen, and tissue homogenates. However, the recognition of the need for a holistic approach to metabolism led to the application of metabolomics to biological fluids for disease diagnostics. A recent surge in metabolomic applications which are probably more accurate than routine clinical practice, dedicated to characterizing the biological fluids. While developments in the analysis of biofluid samples encompassing an important impediment, it must be emphasized that these biofluids are complementary. Metabolomics provides potential advantages that classical diagnostic approaches do not, based on following discovery of a suite of clinically relevant biomarkers that are simultaneously affected by the disease. Emerging as a promising biofocus, metabolomics will drive biofluid analyses and offer great benefits for public health in the long-term. PMID- 22079245 TI - Proteomic analysis of zebrafish (Danio rerio) embryos exposed to cyclosporine A. AB - Cyclosporine A, a potent immunosuppressive agent extensively used to prevent allograft rejections, is under scrutiny due to severe toxic effects. CsA therapy is often continued during pregnancy in conditions such as organ transplantations and autoimmune diseases. Herein, we investigated the effects of CsA on early morphogenesis of zebrafish and identified a spectrum of proteins whose expression was altered in the drug treated embryos. Time-lapse fluorescence imaging of germ line double transgenic zebrafish embryos treated with CsA revealed severe blood regurgitation in heart chambers, absence of blood circulation in vessels, pericardial and yolk sac edema. We also observed lack of mature blood vessels and down-regulation of endothelial markers in CsA treated embryos. Proteomic analysis using 2D-DIGE followed by mass-spectrometry led to the identification of 37 proteins whose expression was significantly modulated in presence of the drug. These proteins were mostly associated with cytoskeletal/structural assembly, lipid-binding, stress response and metabolism. Furthermore, mRNA expression analysis of eight proteins and Western blotting of actin revealed consistency between the changes observed in protein expression and its corresponding mRNA levels. Our findings demonstrate that CsA administration during early morphogenesis in zebrafish modulates the expression of some proteins which are known to be involved in important physiological processes. PMID- 22079246 TI - Analytical constraints for the analysis of human cell line secretomes by shotgun proteomics. AB - Human cell line secretome represents a valuable source of therapeutic targets and candidate biomarkers. Secreted proteins found in biological fluids or culture media are by essence highly diluted. Secretome investigation with proteomic approaches is hardly compatible with the high content of proteins found in complete cell culture media. Therefore, many studies are currently done with media containing few or no protein. Such conditions may perturb cell metabolism and proliferation. Here, we compared seventeen different compositions of culture media for the human bronchial epithelial BEAS-2B cell line. Cell viability, proliferation rate and initial protein charge were systematically compared. We have shown that an important difficulty for the proteomic analysis is due to the presence of detergents such as Pluronic F-68 which hinders peptide mass spectrometry. The high glucose containing DMEM medium which is free of proteins was shown to preserve a good viability and proliferation of cells. With this conditioning medium, we identified 81 extracellular proteins in the secretome of BEAS-2B cells. Moreover, to illustrate this approach, we exposed BEAS-2B cells to a low toxic dose of CoCl(2,) and found 24 extracellular proteins modulated by cobalt. This study highlights the possible contribution of such proteomic approach in the field of toxicology. PMID- 22079247 TI - Physiological response and differential leaf proteome pattern in the European invasive Asteraceae Solidago canadensis colonizing a former cokery soil. AB - Derelict contaminated sites are often colonized spontaneously by plant species leading to a vegetal cover thought to limit particle dispersal and polluted water infiltration. Those plants must cope with soil pollutants through tolerance mechanisms that are not yet fully understood. Here, we focused our attention on a particular Asteraceae plant, Solidago canadensis, considered as invasive in Europe. S. canadensis spontaneously growing on either polluted (NM soil) or control soils dumped on experimental plots were studied for their physiological status, oxidative stress and 2D-DIGE of leaf extracts. S. canadensis tolerance to soil pollutants was demonstrated since growth rates, allocation to reproduction ratios and Fv/Fm ratios were similar in plants from control and NM soil. At the cell level, the catalase activity level was increased in plants collected on NM soil while lipoperoxidation was unaffected. Also, the leaf proteomic study revealed thirty down-regulated and sixty-six up-regulated proteins. Abundances of proteins related to oxidative stress, carbohydrate metabolism, ion transport were mainly up-regulated while those of proteins involved in cell cycle and transcription/translation were mostly down-regulated. Proteins associated to protein metabolism were either down- or up-regulated. Considered altogether, we highlighted that S. canadensis exhibited a complex proteome response when experiencing a multicontaminated soil. PMID- 22079248 TI - Dynamic proteome changes in Campylobacter jejuni 81-176 after high pressure shock and subsequent recovery. AB - Campylobacter jejuni is one of the most intriguing human foodborne bacterial pathogen. Its survival throughout the food processing chain and its pathogenesis mechanisms in humans remain enigmatic. Living in the animal guts and particularly in avian intestine as a commensal bacterium, this microorganism is frequently isolated from meat products. Ultra high pressure (HP) is a promising alternative to thermal technology for microbial safety of foodstuffs with less organoleptic and nutritional alterations. Its application could be extended to meat products potentially contaminated by C. jejuni. To evaluate the response of Campylobacter to this technological stress and subsequent recovery at a molecular level, a dynamic 2-DE-based proteomic approach has been implemented. After cultivation, C. jejuni cells were conditioned in a high-pressure chamber and transferred to fresh medium for recovery. The protein abundance dynamics at the proteome scale were analyzed by 2-DE during the cellular process of cell injury and recovery. Monitoring protein abundance through time unraveled the basic metabolisms involved in this cellular process. The significance of the proteome evolution modulated by HP and subsequent recovery is discussed in the context of a specific cellular response to stress and recovery of C. jejuni with 69 spots showing significant changes through time. PMID- 22079249 TI - Integrin-associated protein (CD47) is a putative mediator for soluble fibrinogen interaction with human red blood cells membrane. AB - Fibrinogen is a multifunctional plasma protein that plays a crucial role in several biological processes. Elevated fibrinogen induces erythrocyte hyperaggregation, suggesting an interaction between this protein and red blood cells (RBCs). Several studies support the concept that fibrinogen interacts with RBC membrane and this binding, due to specific and non-specific mechanisms, may be a trigger to RBC hyperaggregation in inflammation. The main goals of our work were to prove that human RBCs are able to specifically bind soluble fibrinogen, and identify membrane molecular targets that could be involved in this process. RBCs were first isolated from blood of healthy individuals and then separated in different age fractions by discontinuous Percoll gradients. After isolation RBC samples were incubated with human soluble fibrinogen and/or with a blocking antibody against CD47 followed by fluorescence confocal microscopy, flow cytometry acquisitions and zeta potential measurements. Our data show that soluble fibrinogen interacts with the human RBC membrane in an age-dependent manner, with younger RBCs interacting more with soluble fibrinogen than the older cells. Importantly, this interaction is abrogated in the presence of a specific antibody against CD47. Our results support a specific and age-dependent interaction of soluble fibrinogen with human RBC membrane; additionally we present CD47 as a putative mediator in this process. This interaction may contribute to RBC hyperaggregation in inflammation. PMID- 22079250 TI - Comparing the greenhouse gas emissions from three alternative waste combustion concepts. AB - Three alternative condensing mode power and combined heat and power (CHP) waste to-energy concepts were compared in terms of their impacts on the greenhouse gas (GHG) emissions from a heat and power generation system. The concepts included (i) grate, (ii) bubbling fluidised bed (BFB) and (iii) circulating fluidised bed (CFB) combustion of waste. The BFB and CFB take advantage of advanced combustion technology which enabled them to reach electric efficiency up to 35% and 41% in condensing mode, respectively, whereas 28% (based on the lower heating value) was applied for the grate fired unit. A simple energy system model was applied in calculating the GHG emissions in different scenarios where coal or natural gas was substituted in power generation and mix of fuel oil and natural gas in heat generation by waste combustion. Landfilling and waste transportation were not considered in the model. GHG emissions were reduced significantly in all of the considered scenarios where the waste combustion concepts substituted coal based power generation. With the exception of condensing mode grate incinerator the different waste combustion scenarios resulted approximately in 1 Mton of fossil CO(2)-eq. emission reduction per 1 Mton of municipal solid waste (MSW) incinerated. When natural gas based power generation was substituted by electricity from the waste combustion significant GHG emission reductions were not achieved. PMID- 22079251 TI - Modeling of the reburning process using sewage sludge-derived syngas. AB - Gasification of sewage sludge can provide clean and effective reburning fuel for combustion applications. The motivation of this work was to define the reburning potential of the sewage sludge gasification gas (syngas). A numerical simulation of the co-combustion process of syngas in a hard coal-fired boiler was done. All calculations were performed using the Chemkin programme and a plug-flow reactor model was used. The calculations were modelled using the GRI-Mech 2.11 mechanism. The highest conversions for nitric oxide (NO) were obtained at temperatures of approximately 1000-1200K. The combustion of hard coal with sewage sludge-derived syngas reduces NO emissions. The highest reduction efficiency (>90%) was achieved when the molar flow ratio of the syngas was 15%. Calculations show that the analysed syngas can provide better results than advanced reburning (connected with ammonia injection), which is more complicated process. PMID- 22079252 TI - Organic and nitrogen removal from landfill leachate in aerobic granular sludge sequencing batch reactors. AB - Granule sequencing batch reactors (GSBR) were established for landfill leachate treatment, and the COD removal was analyzed kinetically using a modified model. Results showed that COD removal rate decreased as influent ammonium concentration increasing. Characteristics of nitrogen removal at different influent ammonium levels were also studied. When the ammonium concentration in the landfill leachate was 366 mg L(-1), the dominant nitrogen removal process in the GSBR was simultaneous nitrification and denitrification (SND). Under the ammonium concentration of 788 mg L(-1), nitrite accumulation occurred and the accumulated nitrite was reduced to nitrogen gas by the shortcut denitrification process. When the influent ammonium increased to a higher level of 1105 mg L(-1), accumulation of nitrite and nitrate lasted in the whole cycle, and the removal efficiencies of total nitrogen and ammonium decreased to only 35.0% and 39.3%, respectively. Results also showed that DO was a useful process controlling parameter for the organics and nitrogen removal at low ammonium input. PMID- 22079253 TI - Discovery of selective glucocorticoid receptor modulator MK-5932. AB - A series of partial agonists of the Glucocorticoid Receptor were prepared targeting reduced transactivation activity, while maintaining significant transrepression activity. Incorporation of an ortho-aryl amide produced compounds with the desired in vitro profile. Bioreactors consisting of Suspension cultures of Sf21 cells co expressing a CYP3A4 and NADPH-cytochrome P450 oxireductase were used to prepare the major metabolites of these compounds and revealed that oxidative N-dealkylation provided a pathway for formation of metabolites that were more agonistic than the parent partial agonists. Oxidative N-dealkylation was blocked in a new series of compounds, however oxidation alone was capable of producing full agonist metabolites. Incorporation of an ortho-primary amide and utilization of fluorine to modulate agonism afforded partial agonist MK-5932. Synthesis of the major metabolites of MK-5932 using bioreactor technology revealed that no significant GR-active metabolites were formed. Orally administered MK-5932 displayed anti-inflammatory efficacy in a Rat Oxazolone induced chronic dermatitis model, while sparing plasma insulin. PMID- 22079254 TI - Synthesis and antiproliferative evaluation of 6-aryl-11-iminoindeno[1,2 c]quinoline derivatives. AB - A number of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-6-{4-[3 (dimethylamino)propoxy]phenyl}-2-fluoro-9-hydroxy-11H-indeno[1,2-c]quinolin-11 one O-3-(dimethylamino)propyl oxime (23a) was the most active, exhibited GI(50) values of 0.64, 0.39, 0.55, 0.67, and 0.65MUM against the growth of Hep G2, Hep 3B, A549, H1299, and MDA-MB-231, respectively. Compound 23a inhibited the growth of hepatoma cell lines in a dose- and time-dependent manner. The proportion of cells was decreased in the G1 and accumulated in G2/M phase after 12h treatment of 23a, while the hypodiploid (sub-G0/G1 phase) cells increased. Further investigations have shown that 23a induced cell cycle arrest at G2/M phase and induce apoptosis via activation of p53, Bax, and caspase-8 which consequently cause cell death. PMID- 22079255 TI - Characterization and use of a rabbit-anti-mouse VPAC1 antibody by flow cytometry. AB - Vasoactive intestinal peptide receptor-1 signaling in lymphocytes has been shown to regulate chemotaxis, proliferation, apoptosis and differentiation. During T cell activation, VPAC1 mRNA is downregulated, but the effect on its protein levels is less clear. A small number of studies have reported measurement of human VPAC1 by flow cytometry, but murine VPAC1 reagents are unavailable. Therefore, we set out to generate a reliable and highly specific alpha-mouse VPAC1 polyclonal antibody for use with flow cytometry. After successfully generating a rabbit alpha-VPAC1 polyclonal antibody (alpha-mVPAC1 pAb), we characterized its cross-reactivity and showed that it does not recognize other family receptors (mouse VPAC2 and PAC1, and human VPAC1, VPAC2 and PAC1) by flow cytometry. Partial purification of the rabbit alpha-VPAC1 sera increased the specific-activity of the alpha-mVPAC1 pAb by 20-fold, and immunofluorescence microscopy (IF) confirmed a plasma membrane subcellular localization for mouse VPAC1 protein. To test the usefulness of this specific alpha-mVPAC1 pAb, we showed that primary, resting mouse T cells express detectable levels of VPAC1 protein, with little detectable signal from activated T cells, or CD19 B cells. These data support our previously published data showing a downregulation of VPAC1 mRNA during T cell activation. Collectively, we have established a well characterized, and highly species specific alpha-mVPAC1 pAb for VPAC1 surface measurement by IF and flow cytometry. PMID- 22079257 TI - Insights antifibrotic mechanism of methyl palmitate: impact on nuclear factor kappa B and proinflammatory cytokines. AB - Fibrosis accompanies most chronic liver disorders and is a major factor contributing to hepatic failure. Therefore, the need for an effective treatment is evident. The present study was designed to assess the potential antifibrotic effect of MP and whether MP can attenuate the severity of oxidative stress and inflammatory response in chronic liver injury. Male albino rats were treated with either CCl(4) (1 ml/kg, twice a week) and/or MP (300 mg/kg, three times a week) for six weeks. CCl(4)-intoxication significantly increased liver weight, serum aminotransferases, total cholesterol and triglycerides while decreased albumin level and these effects were prevented by co-treatment with MP. As indicators of oxidative stress, CCl(4)-intoxication caused significant glutathione depletion and lipid peroxidation while MP co-treatment preserved them within normal values. As markers of fibrosis, hydroxyproline content and alpha-SMA expression increased markedly in the CCl(4) group and MP prevented these alterations. Histopathological examination by both light and electron microscope further confirmed the protective efficacy of MP. To elucidate the antifibrotic mechanisms of MP, the expression of NF-kappaB, iNOS and COX-2 and the tissue levels of TNF alpha and nitric oxide were assessed; CCl(4) increased the expression of NF kappaB and all downstream inflammatory cascade while MP co-treatment inhibited them. Collectively these findings indicate that MP possesses a potent antifibrotic effect which may be partly a consequence of its antioxidant and anti inflammatory properties. PMID- 22079256 TI - Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. AB - Hexavalent chromium [Cr(VI)] is a human carcinogen that results in the generation of reactive oxygen species (ROS) and a variety of DNA lesions leading to cell death. Epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent antioxidative activity capable of protecting normal cells from various stimuli-induced oxidative stress and cell death. Here we demonstrated that co-treatment with EGCG protected human normal bronchial epithelial BEAS-2B cells from Cr(VI)-induced cell death in a dose-dependent manner. Cr(VI) induces apoptosis as the primary mode of cell death. Co-treatment of BEAS-2B cells with EGCG dose-dependently suppressed Cr(VI)-induced apoptosis. Fluorescence microscopic analyses and quantitative measurement revealed that EGCG significantly decreased intracellular levels of ROS induced by Cr(VI) exposure. Using a well-established K(+)/SDS precipitation assay, we further showed that EGCG was able to dose-dependently reduce DNA-protein cross-links (DPC), lesions that could be partially attributed to Cr(VI)-induced oxidative stress. Finally, analyses of Affymetrix microarray containing 28,869 well-annotated genes revealed that, among the 3412 genes changed more than 1.5-fold by Cr(VI) treatment, changes of 2404 genes (70%) were inhibited by pretreatment of EGCG. Real-time PCR confirmed the induction of 3 genes involved in cell death and apoptosis by Cr(VI), which was eliminated by EGCG. In contrast, Cr(VI) reduced the expression of 3 genes related to cellular defense, and this reduction was inhibited by EGCG. Our results indicate that EGCG protects BEAS-2B cells from Cr(VI)-induced cytotoxicity presumably by scavenging ROS and modulating a subset of genes. EGCG, therefore, might serve as a potential chemopreventive agent against Cr(VI) carcinogenesis. PMID- 22079258 TI - Asymmetric loss of parietal activity causes spatial bias in prodromal and mild Alzheimer's disease. AB - BACKGROUND: In Alzheimer's disease (AD), loss of effective neuronal activity is reflected by cortical glucose hypometabolism. Hypometabolism in the posterior parietal cortex (PPC) is among the first in vivo signs of AD; however, its functional impact on large-scale brain mechanisms and behavior is poorly understood. The lateral PPC contributes to spatial attention constituting a basic function of the human brain. We hypothesized 1) that lateral PPC hypometabolism is associated with impaired spatial attention in very early AD and 2) that impaired competition of effective neuronal activity across hemispheres might underlie this deficit in terms of brain mechanisms. METHODS: A model-based imaging approach was applied to assess patients with prodromal (n = 28) and mild (n = 7) AD. Quantitative attention parameters, derived from performance on simple psychophysical tasks and analyzed by Bundesen's computational theory of visual attention, were related to brain metabolism, measured by (18)F-fluorodeoxyglucose positron emission tomography. RESULTS: Patients' left and right lateral PPC metabolism was reduced. Nine patients had significant spatial attentional bias on the left side and two patients on the right. Direction and degree of spatial bias was correlated with direction and degree of an interhemispheric metabolism bias in the inferior parietal lobe and temporoparietal junction. CONCLUSIONS: Our data provide evidence that in very early AD, asymmetric hypometabolism of the lateral PPC causes spatial attentional bias. Results are broadly consistent with the model that asymmetrically impaired effective neuronal PPC activity in AD biases the competition of visual objects for cortical representation and access to awareness to one side. PMID- 22079259 TI - Prognostic models for outcome following liver resection for colorectal cancer metastases: A systematic review. AB - BACKGROUND: Liver resection provides the best chance for cure in colorectal cancer (CRC) liver metastases. A variety of factors that might influence survival and recurrence have been identified. Predictive models can help in risk stratification, to determine multidisciplinary treatment and follow-up for individual patients. AIMS: To systematically review available prognostic models described for outcome following resection of CRC liver metastases and to assess their differences and applicability. METHODS: The Pubmed, Embase and Cochrane Library databases were searched for articles proposing a prognostic model or risk stratification system for resection of CRC liver metastases. Search terms included 'colorectal', 'liver', 'metastasis', 'resection', 'prognosis' and 'prediction'. The articles were systematically reviewed. RESULTS: Fifteen prognostic systems were identified, published between 1996 and 2009. The median study population was 305 patients and the median follow-up was 32 months. All studies used Cox proportional hazards for multi-variable analysis. No prognostic factor was common in all models, though there was a tendency towards the number of metastases, CRC spread to lymph nodes, maximum size of metastases, preoperative CEA level and extrahepatic spread as representing independent risk factors. Seven models assigned more weight to selected factors considered of higher predictive value. CONCLUSION: The existing predictive models are diverse and their prognostic factors are often not weighed according to their impact. For the development of future predictive models, the complex relations within datasets and differences in relevance of individual factors should be taken into account, for example by using artificial neural networks. PMID- 22079260 TI - Patient, practice and organisational influences on asthma control: observational data from a national study on primary care in the United Kingdom. AB - BACKGROUND: Achieving asthma control is central to optimising patient quality of life and clinical outcome. Contemporary models of chronic disease management across a variety of countries point to the importance of micro, meso and macro level influences on patient care and outcome. However, asthma outcomes research has almost invariably concentrated on identifying and addressing patient predictors. Little is known about higher level organisational influences. OBJECTIVE: This paper explores the contribution of organisational factors on poor asthma control, allowing for patient factors, at three organisational levels: the individual patient, local service deliverers, and strategic regional providers. DESIGN, SETTING AND PARTICIPANTS: Prospective cross-sectional observational cohort study of 64,929 people with asthma from 1205 primary care practices spread throughout the United Kingdom (UK). Patient clinical data were recorded during a routine asthma review. METHOD: Data were analysed using simple descriptive, multiple regression and complex multi-level modelling techniques, accounting for practice clustering of patients. RESULTS: Poor asthma control was associated with areas of higher deprivation [regression coefficient 0.026 (95% confidence intervals 0.006; 0.046)] and urban practice [-0.155 (-0.275; -0.035)] but not all local and regional variation was explained by the data. In contrast, patient level predictors of poor control were: short acting bronchodilator overuse [2.129 (2.091; 2.164)], days-off due to asthma [1.203 (1.148; 1.258)], PEFR<80 [0.76 (0.666; 0.854)], non-use of a self-management plan (SMP) [0.554 (0.515; 0.593)], poor inhaler technique [0.53 (0.475; 0.585)], poor medication compliance [0.385 ( 0.007; 0.777)], and gender [0.314 (0.281; 0.347)]. Pattern of medication use, smoking history, age, body mass index (BMI), and health service resource use were also significant factors for predicting control. CONCLUSIONS: Targeting of health service resource requires knowledge of the factors associated with poor control of asthma symptoms. In the UK the contribution of local and regional structures appears minimal in explaining variation in asthma outcomes. However, unexplained variation in the data suggests other unrecorded factors may play a part. While patient personal characteristics (including self-management plan use, inhaler technique, medication compliance) appear to be the predominant influence the complex nature of the disease means that some, perhaps more subtle, influences are affecting the variability at all levels and this variance needs to be explored. Further research in other international contexts is required to identify the likely applicability of these findings to other health care systems. PMID- 22079261 TI - Having to focus on doing rather than being-nurse assistants' experience of palliative care in municipal residential care settings. AB - BACKGROUND: Palliative care should be provided, irrespective of setting to all patients facing a life-threatening illness and to their families. The situation and needs of older people differ from those of younger people since they often have several co-existing diseases and health complaints. This implies an extensive need for care and for longer periods of palliative care. The main providers of palliative care for older people are nurse assistants, who are also those with the shortest education. AIM: The aim of this study was to illuminate nurse assistants' experience of palliative care for older people in residential care. DESIGN: The study had an explorative, descriptive design. SETTINGS: Thirteen residential care units in three different districts in a large city in southern Sweden. PARTICIPANTS: Twenty-five nurse assistants selected to represent variations in age, gender workplace and work experience. METHODS: Data were collected from six focus-group interviews and subjected to content analysis to gain an understanding of the phenomenon. RESULTS: The nurse assistants described palliative care as a contrast to the everyday care they performed in that they had a legitimate possibility to provide the care needed and a clear assignment in relation to relatives. Palliative care also meant having to face death and dying while feeling simultaneous that it was unnatural to talk about death and having to deal with their own emotions. They emphasised that they were in need of support and experienced leadership as invisible and opaque, but gained strength from being recognized. CONCLUSION: In order to support nurse assistants in providing high quality end-of-life care, more focus is needed on the trajectory of older peoples' dying, on the importance of involving relatives throughout the period of care provision, and on support when encountering death and dying. There is also a need for engaged care leaders, both registered nurses and managers, to recognize the work of nurse assistants and to support care provision for older people within the framework of palliative care philosophy. PMID- 22079262 TI - Long-term outcome of ulcerative colitis in patients who achieve clinical remission with a first course of corticosteroids. AB - BACKGROUND: Although the early outcomes of ulcerative colitis after a first course of corticosteroids are well known, data on long-term disease evolution in patients responding to a first corticosteroid course are scarce. AIMS: To evaluate the long-term clinical evolution in ulcerative colitis patients responding to a first course of corticosteroids and to identify those factors associated with a poorer outcome. METHODS: Retrospective review of 114 patients diagnosed with ulcerative colitis who responded to the first corticosteroid course, and did not start thereafter maintenance therapy with thiopurines were included. RESULTS: Corticosteroids were prescribed because of a moderate (78%) or a severe flare (22%). All but two patients followed maintenance treatment with mesalazine after corticosteroid discontinuation. After a median follow-up of 83 months (7-156), 72% of patients suffered new relapses leading to corticosteroid reintroduction in 65% of patients. The earlier corticosteroids were introduced in the course of ulcerative colitis, the higher the risk of relapse and corticosteroid reintroduction. Thiopurines were started in 51%, and infliximab in 19%. Eleven percent of patients underwent colectomy. No predictors of thiopurine use or colectomy were found. CONCLUSIONS: Half of the ulcerative colitis patients responding to a first course of corticosteroids will require immunosuppressors mainly because of steroid-dependence. PMID- 22079263 TI - Update on the mechanism of action and on clinical efficacy of extracorporeal photopheresis in the treatment of acute and chronic graft versus host disease in children. AB - Extracorporeal photopheresis (ECP) has been used for treatment of steroid refractory graft versus host disease (GVHD) with encouraging results. Although its exact mechanism of action is not fully understood, photoapheresed cells seem to induce a selective immune response directed against alloreactive T cell populations without causing generalized immunosuppression. Current pediatric experience with ECP for GVHD is available in the form of a few retrospective small studies concerning children with steroid refractory GVHD. Reviewing these data we conclude that ECP is a safe procedure, well tolerated even in low-weight pediatric patients, which warrants further evaluation in well-designed, prospective, controlled studies. PMID- 22079264 TI - Comparative levels of macrophage migration inhibitory factor, procalcitonin, osteoprotegerin, interleukin-8, hs-C reactive protein, D-dimer in febrile neutropenia, newly diagnosed cancer patients, and infectious fever. AB - BACKGROUND: The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and D-dimer during fever above 38.3 degrees C due to various causes. MATERIAL AND METHODS: Blood samples taken from a total of consecutive 65 hospitalized patients during fever were prospectively tested for hsCRP, PCT, IL-8, OPG, MIF and D-dimer. Of these patients, there were 26 patients presenting with chemotherapy-induced neutropenia who had no infectious agents found; 23 patients, who had a malignancy with a febrile episode which was neither a microbiologically documented infection nor a chemotherapy-induced neutropenia, and 16 patients who did not have a malignancy and were considered to have a clinically and microbiologically documented infection. RESULTS: IL-8 and D-dimer levels were higher in patients with febrile neutropenia than in the other two groups. Although MIF and OPG were higher in patients with newly diagnosed cancers, there were no differences among the three groups regarding PCT and hs CRP values. CONCLUSION: High serum IL-8 and D-dimer levels can be useful markers to identify hospitalized chemotherapy-induced neutropenia patients. MIF and OPG were found to be higher in patients with newly diagnosed cancer. PMID- 22079266 TI - Saponins from the Spanish saffron Crocus sativus are efficient adjuvants for protein-based vaccines. AB - Protein and peptide-based vaccines provide rigorously formulated antigens. However, these purified products are only weakly immunogenic by themselves and therefore require the addition of immunostimulatory components or adjuvants in the vaccine formulation. Various compounds derived from pathogens, minerals or plants, possess pro-inflammatory properties which allow them to act as adjuvants and contribute to the induction of an effective immune response. The results presented here demonstrate the adjuvant properties of novel saponins derived from the Spanish saffron Crocus sativus. In vivo immunization studies and tumor protection experiments unambiguously establish the value of saffron saponins as candidate adjuvants. These saponins were indeed able to increase both humoral and cellular immune responses to protein-based vaccines, ultimately providing a significant degree of protection against tumor challenge when administered in combination with a tumor antigen. This preclinical study provides an in depth immunological characterization of a new saponin as a vaccine adjuvant, and encourages its further development for use in vaccine formulations. PMID- 22079265 TI - Protective immunity against mouse upper genital tract pathology correlates with high IFNgamma but low IL-17 T cell and anti-secretion protein antibody responses induced by replicating chlamydial organisms in the airway. AB - To search for optimal immunization conditions for inducing protective immunity against upper genital tract pathologies caused by chlamydial intravaginal infection, we compared protection efficacy in mice immunized intranasally or intramuscularly with live or inactivated Chlamydia muridarum organisms. Mice immunized intranasally with live organisms developed strong protection against both vaginal shedding of infectious organisms and upper genital tract pathologies. The protection correlated with a robust antigen-specific T cell response with high IFNgamma but low IL-17. Although a significant level of IL-5 was also detected, these mice maintained an overall Th1-dorminant immunity following immunization and challenge infection. On the contrary, mice immunized intranasally with inactivated organisms or intramuscularly with live or inactivated organisms produced high levels of IL-17 and still developed significant upper genital tract pathologies. High titers of antibodies against chlamydial secretion antigens were detected only in mice immunized intranasally with live organisms but not mice in other groups, suggesting that the intranasally inoculated live organisms were able to undergo replication and immune responses to the chlamydial secretion proteins may contribute to protective immunity. These observations have provided important information on how to develop subunit vaccines for inducing protective immunity against urogenital infection with Chlamydia trachomatis organisms. PMID- 22079267 TI - Birth order and private voluntary immunization--a study of 110,902 children. AB - BACKGROUND: Introduction of new private, voluntary immunizations often results in low vaccine uptake among certain sub-groups within the population. Revealing factors associated with underimmunization is crucial in vaccine endorsement and distribution. OBJECTIVE: Our goal was to investigate the effect of child's birth order on private voluntary varicella vaccination. METHODS: A nested case-control study was conducted on a cohort of 110,902 Israeli children under the age of 5 years. We compared social and demographic factors of immunized and unimmunized participants. Logistic regression models were built to examine the association between birth order and vaccination, controlling for child's age, gender, country of birth, ethnicity, parents' country of birth, area of residence, and socioeconomic status (SES). RESULTS: Ethnicity had the highest association with varicella immunization status. The odds of vaccination in the general Jewish and Ultra-Orthodox Jewish populations were 25.55- (95%CI:20.13;32.42) and 15.04- (95%CI:10.18;22.22) times the odds in Arab population, respectively. Child's birth order was inversely related to vaccination status and presented a nonlinear exposure-response relationship. This relationship was maintained in different ethnicity and SES groups. Child's birth order was associated with vaccination differently in large (> 3 siblings) and small to average-sized sibships (<= 3 siblings). Other parameters associated with vaccination were child's and parents' country of origin, area of residence and SES. CONCLUSIONS: Birth order is an independent risk factor for underimmunization, associated with child's vaccination status beyond economic, social, and demographic parental characteristics. PMID- 22079269 TI - Transcriptional networks and chromatin remodeling controlling adipogenesis. AB - Adipocyte differentiation is tightly controlled by a transcriptional cascade, which directs the extensive reprogramming of gene expression required to convert fibroblast-like precursor cells into mature lipid-laden adipocytes. Recent global analyses of transcription factor binding and chromatin remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications. Such transcription factor hotspots are likely to represent key signaling nodes which integrate multiple adipogenic signals at specific chromatin sites, thereby facilitating coordinated action on gene expression. PMID- 22079268 TI - Genetic defects in the hotspot of inwardly rectifying K(+) (Kir) channels and their metabolic consequences: a review. AB - Inwardly rectifying potassium (Kir) channels are essential for maintaining normal potassium homeostasis and the resting membrane potential. As a consequence, mutations in Kir channels cause debilitating diseases ranging from cardiac failure to renal, ocular, pancreatic, and neurological abnormalities. Structurally, Kir channels consist of two trans-membrane domains, a pore-forming loop that contains the selectivity filter and two cytoplasmic polar tails. Within the cytoplasmic structure, clusters of amino acid sequences form regulatory domains that interact with cellular metabolites to control the opening and closing of the channel. In this review, we present an overview of Kir channel function and recent progress in the characterization of selected Kir channel mutations that lie in and near a C-terminal cytoplasmic 'hotspot' domain. The resultant molecular mechanisms by which the loss or gain of channel function leads to organ failure provide potential opportunities for targeted therapeutic interventions for this important group of channelopathies. PMID- 22079270 TI - A neural model of sequential movement planning and control of eye movements: Item Order-Rank working memory and saccade selection by the supplementary eye fields. AB - How does working memory store multiple spatial positions to control sequences of eye movements, particularly when the same items repeat at multiple list positions, or ranks, during the sequence? An Item-Order-Rank model of working memory shows how rank-selective representations enable storage and recall of items that repeat at arbitrary list positions. Rank-related activity has been observed in many areas including the posterior parietal cortices (PPC), prefrontal cortices (PFC) and supplementary eye fields (SEF). The model shows how rank information, originating in PPC, may support rank-sensitive PFC working memory representations and how SEF may select saccades stored in working memory. It also proposes how SEF may interact with downstream regions such as the frontal eye fields (FEF) during memory-guided sequential saccade tasks, and how the basal ganglia (BG) may control the flow of information. Model simulations reproduce behavioral, anatomical and electrophysiological data under multiple experimental paradigms, including visually- and memory-guided single and sequential saccade tasks. Simulations reproduce behavioral data during two SEF microstimulation paradigms, showing that their seemingly inconsistent findings about saccade latency can be reconciled. PMID- 22079272 TI - Emotional memory: synthesis of a study proposal. PMID- 22079273 TI - Occiput to thoracic fusion after surgical resection of desmoid tumor. AB - BACKGROUND: Desmoid tumors are rare clinical entities that cause significant morbidity based on their locally aggressive nature. Complete resection with wide margins is the standard of care; however, when arising in the neck, resection is limited due to proximity of the lesion to critical structures. CASE DESCRIPTION: We describe a complete resection of a desmoid tumor requiring extensive resection of cervical extensor musculature. We were able to achieve a total resection of a cervical desmoid tumor with no evidence of recurrence at follow-up. CONCLUSIONS: Complete resection of desmoid tumors is the standard of care. In this case, we felt that complete resection would lead to iatrogenic instability; therefore, an occiput to thoracic fusion was performed at the time of the resection. PMID- 22079274 TI - Stereotactic biopsy with electrical monitoring for deep-seated brain tumors. AB - OBJECTIVE: The stereotactic biopsy is widely integrated into clinical practice as an efficient and safe procedure for histologic diagnoses. However, the surgical risk increases when the lesions are close to the eloquence of the adjacent brain. The present report describes two patients with deep-seated brain tumors who underwent a stereotactic biopsy with electrical monitoring and demonstrates the importance of this technique. METHODS: The tentative target and trajectory were determined on a stereotactic map from the Schaltenbrand and Wahren atlas. A Cosman-Roberts-Wells stereotactic frame was applied to the patient. Electrical recording along a single trajectory was used to identify the circumscribed neuronal structures, and electrical simulation was administered to the target. The biopsy point was decided when no adverse events were observed with a low electric current level. RESULTS: A 34-year-old male patient with anaplastic astrocytoma in the putamen and thalamus and an 81-year-old female patient with malignant lymphoma in the midbrain underwent stereotactic biopsies with electrical monitoring. The biopsies were successfully performed without any resulting neurologic deficits. CONCLUSIONS: This report describes two patients with deep-seated brain tumors who underwent stereotactic biopsies with electrical recording and stimulation. The electrical monitoring appears to be a useful technique to complement the ordinary image-guided biopsy. PMID- 22079275 TI - Predicting symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage: are we there yet? PMID- 22079276 TI - Surgical strategies in the management of cervical degenerative disorders. PMID- 22079277 TI - Motor palsy after posterior cervical foraminotomy: anatomical consideration. AB - BACKGROUND: Motor palsy is a serious complication that can result from cervical surgery. We introduced cases of motor palsy after posterior cervical foraminotomy (PCF) and consider cervical anatomy. METHODS: Between January 2007 and August 2010, 133 PCFs were performed on 106 consecutive patients with radiculopathy caused by foraminal stenosis or posterolateral disc herniation. RESULTS: Three of 133 (2.3%) levels that underwent PCF developed a motor palsy. Two cases involved the C5 nerve root, and one case involved the C6 nerve root. The cause of the C5 palsy may have been excessive retraction, whereas the cause of the C6 palsy may have been thermal damage caused by drilling. The rate of C5 palsy (22.2%) was much higher than that seen with other nerves. Anatomically, the C5 nerve root is thinner and covers the entire intervertebral disc at a relatively sharper angle than the other nerve roots. The removal of an extruded disc at C4-5 forces more excessive retraction of the C5 nerve root. CONCLUSIONS: Although PCF is a good alternative treatment with minimal morbidity for cervical radiculopathy, surgeons should keep in mind the possibility of motor palsy, especially at C4-5. PMID- 22079278 TI - Intraoperative patient-specific reconstruction of partial bone flap defects after convexity meningioma resection. AB - OBJECTIVE: To evaluate implant accuracy and cosmetic outcome of a new intraoperative patient-specific cranioplasty method after convexity meningioma resection. METHODS: The patient's own bone flap served as a template to mold a negative form with the use of polymethyl methacrylate (PMMA). The area of bone invasion was determined and broadly excised under white light illumination with a safety margin of at least 1 cm. The definitive replica was cast within the remaining bone flap frame and the imprint. Clinical and radiologic follow-up examinations were performed 3 months after surgery. RESULTS: Four women and two men (mean age 51.4 years+/-12.8) underwent reconstruction of bone flap defects after meningioma resection. Mean duration of intraoperative reconstruction of the partial bone flap defects was 19 minutes+/-4 (range 14-24 minutes). Implant sizes ranged from 17-35 cm2 (mean size 22 cm2+/-8). Radiologic and clinical follow-up examinations revealed excellent implant alignment and favorable cosmesis (visual analogue scale for cosmesis [VASC]=97+/-5) in all patients. CONCLUSIONS: Patient specific reconstruction of partial bone flap defects after convexity meningioma resection using the presented intraoperative PMMA cast method resulted in excellent bony alignment and a favorable cosmetic outcome. Relatively low costs and minimized operation time for adjustment and insertion of the cranioplasty implant justify use of this method in small bony defects as well. PMID- 22079279 TI - Analysis of venous drainage from sylvian veins in clinoidal meningiomas. AB - OBJECTIVE: To categorize clinoidal meningiomas according to their venous drainage patterns, and use each category as a guideline to establish an appropriate surgical strategy. METHODS: We performed a retrospective analysis of 22 consecutive surgically treated patients with clinoidal meningioma who underwent preoperative digital subtraction angiography to examine the characteristics of the venous drainage system. These patients were categorized into: 1) cortical type in which the sylvian vein did not drain medially but drained to cortical veins, 2) sphenobasal type in which the sylvian vein drained into the pterygoid plexus, or 3) cavernous type in which the sylvian vein drained into the cavernous sinus directly through the sphenoparietal sinus. We tailored the surgical strategy to preserve these draining veins. RESULTS: Preoperative angiographic evaluation demonstrated 14 patients (63.6%) with cortical type, 6 patients (27.3%) with sphenobasal type, and 2 patients (9.1%) with the cavernous type. In most cases, no restriction from the venous structure was observed because the sylvian vein belonged to the cortical type. However, in the case of the sphenobasal or sphenoparietal type, the surgical strategy seemed to be tailored to preserve the venous drainage system. CONCLUSIONS: The surgical risk from venous complication in the treatment of clinoidal meningiomas appears to be low; however, there are likely to be patients that require a tailored surgical approach to avoid venous complications. Detailed preoperative assessment of anatomic structure and consideration of the optimal surgical strategy are critical to improve treatment outcomes. PMID- 22079280 TI - Adrenocorticotropic hormone-producing pituitary carcinoma with intracranial metastases. AB - BACKGROUND: Pituitary carcinomas are rare and challenging clinical entities. Because of the paucity of cases, there is limited information in the literature on how best to diagnose and treat pituitary carcinomas. METHODS: We review the literature and describe a woman who presented with an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma that later evolved into a carcinoma with intracranial metastases. RESULTS: A 39-year-old woman presented at age 27 with classic findings of Cushing's syndrome and a pituitary macroadenoma. Her initial treatment was transsphenoidal surgery, during which we confirmed an ACTH secreting pituitary neoplasm. For 5 years, she was asymptomatic before her first recurrence. During the next 6 years, she underwent four transsphenoidal surgeries and two craniotomies. After each surgery, there was some reduction in the size of the macroadenoma but the residual tumor mass would rapidly enlarge. Immunochemical staining was positive for ACTH, and a stain for Ki-67 antigen showed a high mitotic index. Eleven years after her initial presentation, magnetic resonance imaging revealed bilateral hippocampal and tempero-occipital masses. The patient's health continued to deteriorate, largely from complications of severe hypercortisolemia, and she died from sepsis. At postmortem, the hippocampus and tempero-occipital lobe masses proved to be a pituitary tumor with positive ACTH staining. CONCLUSIONS: Pituitary carcinomas are rare, may present many years after diagnosis of a primary pituitary adenoma, and should be suspected in patients with persistent or recurrent disease. Reliable histopathologic ways to distinguish between carcinoma and adenoma are difficult because the features of hypercellularity, nuclear pleomorphism, and mitotic figures are not always helpful. PMID- 22079281 TI - Male only progeny in Anastrepha suspensa by RNAi-induced sex reversion of chromosomal females. AB - In Tephritidae sex determination is established by orthologs to the Drosophila melanogaster transformer and transformer-2 genes, though the primary signals for sex determination differ. The presence of the Y chromosome in the tephritid species is critical for male differentiation, while the ratio of X chromosomes to autosome ploidy is critical in drosophilids. Here the isolation, expression and function of tra and tra-2 orthologs are described for the agriculturally important tephritid, Anastrepha suspensa, and their possible use in genetically modified organisms for biologically-based pest management. The Astra and Astra-2 genes are highly conserved in structure, regulation and function with respect to those known from other tephritid species. Sex-specific transcripts for Astra were detected, one in females and three in males, whereas Astra-2 had a single common transcript found in both sexes. To test the function of these genes, Astra and Astra-2 dsRNA was injected into A. suspensa embryos from a transgenic strain having a Y-linked DsRed marker integration, allowing XY males to be distinguished from XX phenotypic males. Nearly all XX embryos developed into fully masculinized phenotypic male adults with no apparent female morphology. Upon dissection abnormal hypertrophic gonads were revealed in XX pseudomales but not in the XY males. Our findings suggest that Astra and Astra-2 are both necessary for female development, and that the potential exists for producing a male-only population when either gene alone, or both genes simultaneously, are knocked-down. PMID- 22079282 TI - Dentistry and population approaches for preventing dental diseases. AB - Dental professionals are expected to engage in oral disease prevention, but their tools limit the approach to chair side activities based on the common notion that the major dental diseases, dental caries, gingivitis and periodontitis, are behavioural diseases shaped by individual lifestyles. However, lifestyles also have causes and individual behaviours reflect cultural norms, expectations and opportunities that are socio-economically determined and structurally maintained. Importantly, the effects of the societal and socio-economic determinants reach way above their influences as individual attributes, and effective approaches to the prevention and control of oral diseases are aligned with this causal chain. Unfortunately, the ethos and philosophy of dentistry is focused to a downstream, patient-centred, curative and rehabilitative approach to oral diseases. Whilst such services are needed to care for those who have already suffered the consequences of oral diseases, they do not influence population oral health. A more balanced distribution of efforts and resources along the whole range of intervention points from the downstream curative to the upstream structural healthy policy approaches is required if appropriate, evidence-based, effective, cost-effective, sustainable, equitable, universal, comprehensive and ethical delivery of health care, including oral health care, is the goal. The implementation of healthy policies and sound approaches to population oral health will require substantial commitment and political will on the part of the public and their elected officials. PMID- 22079284 TI - Glucose: a vital toxin and potential utility of melatonin in protecting against the diabetic state. AB - The molecular mechanisms including elevated oxidative and nitrosative reactants, activation of pro-inflammatory transcription factors and subsequent inflammation appear as a unified pathway leading to metabolic deterioration resulting from hyperglycemia, dyslipidemia, and insulin resistance. Consistent evidence reveals that chronically-elevated blood glucose initiates a harmful series of processes in which toxic reactive species play crucial roles. As a consequence, the resulting nitro-oxidative stress harms virtually all biomolecules including lipids, proteins and DNA leading to severely compromised metabolic activity. Melatonin is a multifunctional indoleamine which counteracts several pathophysiologic steps and displays significant beneficial effects against hyperglycemia-induced cellular toxicity. Melatonin has the capability of scavenging both oxygen and nitrogen-based reactants and blocking transcriptional factors which induce pro-inflammatory cytokines. These functions contribute to melatonin's antioxidative, anti-inflammatory and possibly epigenetic regulatory properties. Additionally, melatonin restores adipocyte glucose transporter-4 loss and eases the effects of insulin resistance associated with the type 2 diabetic state and may also assist in the regulation of body weight in these patients. Current knowledge suggests the clinical use of this non-toxic indoleamine in conjunction with other treatments for inhibition of the negative consequences of hyperglycemia for reducing insulin resistance and for regulating the diabetic state. PMID- 22079283 TI - Regulation of reactionary dentin formation by odontoblasts in response to polymicrobial invasion of dentin matrix. AB - Odontoblast synthesis of dentin proceeds through discrete but overlapping phases characterized by formation of a patterned organic matrix followed by remodelling and active mineralization. Microbial invasion of dentin in caries triggers an adaptive response by odontoblasts, culminating in formation of a structurally altered reactionary dentin, marked by biochemical and architectonic modifications including diminished tubularity. Scanning electron microscopy of the collagen framework in reactionary dentin revealed a radically modified yet highly organized meshwork as indicated by fractal and lacunarity analyses. Immuno-gold labelling demonstrated increased density and regular spatial distribution of dentin sialoprotein (DSP) in reactionary dentin. DSP contributes putative hydroxyapatite nucleation sites on the collagen scaffold. To further dissect the formation of this altered dentin matrix, the associated enzymatic machinery was investigated. Analysis of extracted dentin matrix indicated increased activity of matrix metalloproteinase-2 (MMP-2) in the reactionary zone referenced to physiologic dentin. Likewise, gene expression analysis of micro-dissected odontoblast layer revealed up-regulation of MMP-2. Parallel up-regulation of tissue inhibitor of metalloproteinase-2 (TIMP-2) and membrane type 1- matrix metalloproteinase (MT1-MMP) was observed in response to caries. Next, modulation of odontoblastic dentinogenic enzyme repertoire was addressed. In the odontoblast layer expression of Toll-like receptors was markedly altered in response to bacterial invasion. In carious teeth TLR-2 and the gene encoding the corresponding adaptor protein MyD88 were down-regulated whereas genes encoding TLR-4 and adaptor proteins TRAM and Mal/TIRAP were up-regulated. TLR-4 signalling mediated by binding of bacterial products has been linked to up-regulation of MMP 2. Further, increased expression of genes encoding components of the TGF-beta signalling pathway, namely SMAD-2 and SMAD-4, may explain the increased synthesis of collagen by odontoblasts in caries. These findings indicate a radical adaptive response of odontoblasts to microbial invasion of dentin with resultant synthesis of modified mineralized matrix. PMID- 22079285 TI - Bradykinin receptor 2 extends inflammatory cell recruitment in a model of acute gouty arthritis. AB - The aim of this study was determine the effect of bradykinin receptor antagonism on MSU crystal-induced chemokine production and leukocyte recruitment. Mice were injected intraperitoneally with monosodium urate (MSU) crystals +/- bradykinin B1 or B2 receptor antagonists, Des-Arg-HOE-140 and HOE-140, respectively. MSU crystal-induced chemokine production and leukocyte recruitment in the peritoneum were measured over 24h and B1 and B2 receptor expression on leukocytes and peritoneal membrane was determined by flow cytometry and fluorescence microscopy. Data analysis showed that only B2 receptor antagonism decreased monocyte and neutrophil infiltration 24 h post MSU crystal administration. Decreased leukocyte infiltration was associated with reduced monocyte (CCL2) chemokine levels. MSU crystal-induced damage to the surrounding visceral membrane was also attenuated in the presence of B2 receptor antagonism. Together, these data show that bradykinin receptor 2 plays a role in maintaining MSU crystal-induced leukocyte infiltration and membrane permeability and identify the B2 receptor as a potential therapeutic target for managing inflammation in gout. PMID- 22079286 TI - Adrenomedullin: a possible regulator of germinal vesicle breakdown. AB - Adrenomedullin (ADM) is a multifunctional hormone that regulates processes as diverse as blood pressure and cell growth. Although expressed in the ovary, the role of ADM in this organ is not clear. In the present study, we found the expression of ADM receptor and receptor activity-modifying proteins in mouse cumulus cells but not in the oocytes. We report that germinal vesicle breakdown (GVBD), which is required for oocyte maturation, is not inhibited by ADM alone. However, ADM in the presence of the nitric oxide donor sodium nitroprusside (SNP) significantly inhibited GVBD. Furthermore, the ADM- and SNP-dependent inhibition of GVBD was abrogated by Akt blockade. Additionally, Akt expression and phosphorylation was exhibited by ADM, suggesting that Akt signaling upstream in cumulus cells is responsible. Additionally, immunohistochemical analysis revealed that ADM was localized in the granulosa cells of developed follicles, implying the possibility that ADM physiologically affects oocyte maturation in vivo. Our results provide the evidence that ADM can act as a GVBD regulator. PMID- 22079287 TI - 5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion. AB - GPR119 is one of the G-protein-coupled receptors expressed in pancreatic beta cells and intestinal endocrine cells. Since agonists to GPR119 stimulate glucose dependent insulin secretion, GPR119 agonists are anticipated to promote anti diabetic effects and control of glucose homeostasis. Here, we reported that an omega-3 unsaturated fatty acid metabolite, 5-hydroxy-eicosapentaenoic acid (5 HEPE), was a potent agonist for GPR119 and enhanced glucose-dependent insulin secretion. 5-HEPE stimulated cAMP accumulation in mouse MIN6 insulinoma cells and human HuTu80 intestinal adenocarcinoma cells. These effects were blunted by GPR119-specific siRNA. Recombinant GPR119 also responded to 5-HEPE as well as authentic agonists. Several previous reports have indicated the beneficial biological effects of omega-3 unsaturated fatty acids, and epidemiological studies have suggested that these fatty acids plays a protective role against diabetes. However, the molecular pharmacology and receptor identifications of omega-3 unsaturated fatty acids and their metabolites have not yet been well investigated. It is hoped that our findings will encourage novel investigations into the molecular relationships between omega-3 fatty acids and diabetes. PMID- 22079288 TI - Quercetin inhibits amyloid fibrillation of bovine insulin and destabilizes preformed fibrils. AB - Growing interest and research efforts have recently been focused on elucidating the molecular mechanism of amyloid formation and the screening of effective inhibitors to interrupt amyloid structures. In the present study, the anti amyloidogenic effects of quercetin were investigated in vitro using bovine insulin as a model protein. The results demonstrated that quercetin dose dependently inhibited amyloid formation of insulin. Moreover, quercetin destabilized the preformed insulin fibrils and transformed the fibrils into amorphous aggregates. Hemolysis was observed when human erythrocytes were co incubated with insulin fibrils. Quercetin inhibited fibril-induced hemolysis in a dose-dependent manner. SDS-PAGE showed that insulin fibrils induced the aggregation of cytoskeletal proteins of erythrocyte membranes and that quercetin attenuated this fibril-induced cytoskeletal aggregation. The results of the present work suggest that quercetin may serve as a lead structure for the design of novel anti-amyloidogenic drugs. PMID- 22079289 TI - Increased salt and drought tolerance by D-ononitol production in transgenic Arabidopsis thaliana. AB - The methylation of myo-inositol forms O-methyl inositol (D-ononitol) when plants are under abiotic stress in a reaction catalyzed by myo-inositol methyltransferase (IMT). D-Ononitol can serve as an osmoprotectant that prevents water loss in plants. We isolated the IMT cDNA from Glycine max and found by RT PCR analysis that GmIMT transcripts are induced by drought and salinity stress treatments in the leaves of soybean seedlings. We confirmed the protein product of GmIMT and its substrate using a recombinant system in E. coli. Transgenic Arabidopsis plants over-expressing GmIMT displayed improved tolerance to dehydration stress treatment and to a lesser extent high salinity stress treatment. These results indicate that GmIMT is functional in heterologous Arabidopsis plants. PMID- 22079290 TI - High density cultures of embryoid bodies enhanced cardiac differentiation of murine embryonic stem cells. AB - Murine embryonic stem cell (mESC)-derived cardiomyocytes represent a promising source of cells for use in the development of models for studying early cardiac development as well as cell-based therapies in postnatal pathologies. Here, we report a highly efficient cardiac differentiation system in which high density embryoid body (EB) cultures leads to a marked increase of cardiomyocytes production from multiple mESC lines without the addition of any cardiogenic growth factors. Our results show that high density EB cultures significantly increase the yield of functional cardiomyocytes, which express typical cardiac markers, exhibit normal rhythmic Ca(2+) transients, and respond to both beta adrenergic and electric stimulations. During the differentiation period, the inhibition of bone morphogenetic protein (BMP) signaling significantly attenuates the increase of cardiac differentiation as well as the increased expression of cardiac-specific genes, NK2 transcription factor related 5 (Nkx2.5) and myosin light chain 2v (Mlc2v) by high density EB cultures. Therefore, we believe that we offer a novel and efficient means of cardiomyocyte production for practical use of mESCs in cardiac regenerative medicine. PMID- 22079291 TI - SAXS data analysis and modeling of tetravalent neutralizing antibody CD4-IgG2 -/+ HIV-1 gp120 revealed that first two gp120 bind to the same Fab arm. AB - This communication describes SAXS data based global structures of tetravalent antibody CD4-IgG2 and its dimeric to pentameric complexes with gp120s. Comparison of models brought forth that while the two CD4s grafted on each arm remain tightly packed in the unliganded antibody, they enable binding of first two gp120s preferentially to the same Fab arm in an asymmetric manner. Retention of residues in the CD4-Fab linker earlier reasoned to enable bi-fold collapse of gp120-bound soluble CD4, and observed asymmetry of the (CD4-IgG2)/(gp120)(2) complex suggest that encoded flexibility in CD4-Fab linker is a critical structure-function factor for this broad spectrum neutralizing antibody. PMID- 22079293 TI - Protein prenylation: a new mode of host-pathogen interaction. AB - Post translational modifications are required for proteins to be fully functional. The three step process, prenylation, leads to farnesylation or geranylgeranylation, which increase the hydrophobicity of the prenylated protein for efficient anchoring into plasma membranes and/or organellar membranes. Prenylated proteins function in a number of signaling and regulatory pathways that are responsible for basic cell operations. Well characterized prenylated proteins include Ras, Rac and Rho. Recently, pathogenic prokaryotic proteins, such as SifA and AnkB, have been shown to be prenylated by eukaryotic host cell machinery, but their functions remain elusive. The identification of other bacterial proteins undergoing this type of host-directed post-translational modification shows promise in elucidating host-pathogen interactions to develop new therapeutics. This review incorporates new advances in the study of protein prenylation into a broader aspect of biology with a focus on host-pathogen interaction. PMID- 22079292 TI - Store-operated calcium entry is present in HL-1 cardiomyocytes and contributes to resting calcium. AB - Store-operated Ca(2+) entry (SOCE) has recently been shown to be of physiological and pathological importance in the heart, particularly during cardiac hypertrophy. However, measuring changes in intracellular Ca(2+) during SOCE is very difficult to study in adult primary cardiomyocytes. As a result there is a need for a stable and reliable in vitro model of SOCE which can be used to test cardiac drugs and investigate the role of SOCE in cardiac pathology. HL-1 cells are the only immortal cardiomyocyte cell line available that continuously divides and spontaneously contracts while maintaining phenotypic characteristics of the adult cardiomyocyte. To date the role of SOCE has not yet been investigated in the HL-1 cardiac cell line. We report for the first time that these cells expressed stromal interaction molecule 1 (STIM1) and the Ca(2+) release-activated Ca(2+) (CRAC) channel Orai1, which are essential components of the SOCE machinery. In addition, SOCE was tightly coupled to sarcoplasmic reticulum (SR) Ca(2+) release in HL-1 cells, and such response was not impaired in the presence of voltage dependent Ca(2+) channels (L-type and T-type channels) or reverse mode Na(+)/Ca(2+) exchanger (NCX) inhibitors. We were able to abolish the SOCE response with known SOCE inhibitors (BTP-2 and SKF-96365) and by targeted knockdown of Orai1 with RNAi. In addition, knockdown of Orai1 resulted in lower baseline Ca(2+) and an attenuated response to thapsigargin (TG) and caffeine, indicating that SOCE may play a role in Ca(2+) homeostasis during unstressed conditions in cardiomyocytes. Currently, there is little knowledge about SOCE in cardiomyocytes, and the present results suggest that HL-1 cells will be of great utility in investigating the role of SOCE in the heart. PMID- 22079294 TI - An epifluorescence microscopy method for generalized polarization imaging. AB - Generalized polarization (GP) microscopy represents an excellent tool to study lipid-lipid and lipid-protein interactions in situ and in vitro. Here, we present an efficient and cost effective method to perform GP microscopy using a standard light-emitting diode (LED) epifluorescence microscope equipped with a digital color camera. PMID- 22079295 TI - The AMPA receptor potentiator Org 26576 modulates stress-induced transcription of BDNF isoforms in rat hippocampus. AB - Brain derived neurotrophic factor (BDNF) is a key mediator of brain plasticity. The modulation of its expression and function is important for cognition and represents a key strategy to enhance neuronal resilience. Within this context, there exists a close interaction between glutamatergic neurotransmission and BDNF activity towards regulating cellular homeostasis and plasticity. The aim of the current study was to investigate the ability of the AMPA receptor potentiator Org 26576 to modulate BDNF expression in selected brain regions under basal conditions or in response to an acute swim stress. Rats subjected to a single intraperitoneal injection with Org 26576 (10mg/kg) or saline were exposed to a swim stress session (5 min) and sacrificed 15 min after the end of stress. Real time PCR assay was used to determine changes in BDNF transcription in different brain regions. Total BDNF mRNA levels were significantly increased in the hippocampus of animals exposed to the combination of Org 26576 and stress whereas, in prefrontal and frontal cortices, BDNF mRNA levels were modulated by the acute stress, independently from drug treatment. The analysis of BDNF transcripts in the hippocampus revealed a major contribution of exons I and IV. Our results suggest that AMPA receptor potentiation by Org 26576 exerts a positive modulatory influence on BDNF expression during ongoing neuronal activity. Given that these mechanisms are critical for neuronal plasticity, we hypothesized that such changes may facilitate learning/coping mechanisms associated with a mild stressful experience. PMID- 22079296 TI - Ecological and molecular consequences of prolonged drought and subsequent rehydration in Folsomia candida (Collembola). AB - Drought tolerance in water-permeable, soil-living Collembola (e.g. Folsomia candida) is achieved due to a unique water vapour absorption mechanism, where accumulation of sugars and polyols is essential. However, the molecular mechanisms underlying such adaptation as well as the maintenance of this survival strategy and the responses to rehydration after prolonged drought in these soil living Collembola are unclear. In the present study, the functional relationships between ecological drought responses and expression of related target genes were investigated in F. candida exposed to mild and severe drought for up to 5 weeks by relating survival, moulting and reproduction rate with mRNA-level expression of 7 target genes during drought, dehydration and rehydration. Prolonged drought and subsequent rehydration induced significant changes in gene expression which could be related to the fitness traits studied. In F. candida the ecological and molecular responses to mild drought differed from those of severe drought. From the changes in gene expression, where significantly increased expression of Glucose-6-phosphate-isomerase (gpi) and Heat shock protein 70 (hsp70) was dominating, it is proposed that protection of cellular structure and function during prolonged mild drought (98.2% RH) is partly achieved from a continuous accumulation of compatible osmolytes in F. candida. To achieve protection during and after prolonged severe drought (96.1% RH), components related to cell division and development such as inositol monophosphatase and one of the small heat shock proteins (sHsps), Heat shock protein23 (hsp23), seem to play an important role in F. candida. PMID- 22079297 TI - Venom lethality and diet: differential responses of natural prey and model organisms to the venom of the saw-scaled vipers (Echis). AB - The composition of snake venoms shows a high degree of variation at all taxonomic levels, and natural selection for diet has been implicated as a potential cause. Saw-scaled vipers (Echis) provide a good model for studying this phenomenon. The venoms of arthropod feeding species of Echis are significantly more toxic to natural scorpion prey than those of species which feed predominantly upon vertebrate prey. Although testing venom activity on natural prey is important for our understanding of the evolution of venom, natural prey species are often difficult to obtain in sufficient numbers for toxinological work. In order to test the viability of using cheaper and more easily available model organisms for toxicity assessments in evolutionary research, and the extent to which toxicity of arthropod-eating Echis venoms is increased to arthropods in general or targeted to certain groups, we conducted median lethal dosage (LD(50)) and time to death trials using the desert locust (Schistocerca gregaria) as a model arthropod, rarely consumed by wild Echis. The venoms of arthropod specialist Echis were found to be significantly more toxic to locusts than the venom of a vertebrate feeding outgroup (Bitis arietans), and one arthropod specialist venom was found to be more toxic than those species which feed upon arthropods infrequently or not at all. The venoms of arthropod specialists were also found to cause death and incapacitation faster than the vertebrate feeding outgroup. Despite some similarity of trends, there are considerable differences between the response of natural prey (scorpions) and a model arthropod (locust) to the venoms of Echis species. This suggests that when possible, natural prey rather than convenient model organisms should be used to gain an understanding of the functional significance of variation in venom composition in snakes. PMID- 22079298 TI - BJcuL, a lectin purified from Bothrops jararacussu venom, induces apoptosis in human gastric carcinoma cells accompanied by inhibition of cell adhesion and actin cytoskeleton disassembly. AB - We show that BJcuL, a lectin purified from Bothrops jararacussu venom, exerts cytotoxic effects to gastric carcinoma cells MKN45 and AGS. This effect was due to the direct interaction with specific glycans on the cells surface and was observed by cell viability decrease, disorganization of actin filaments and apoptosis. In addition, BJcuL was able to reduce tumor cell adhesion to matrigel, what was inhibited by specific carbohydrate or partially inhibited when cells were pre-incubated with matrigel. Our results suggest that BJcuL was able to promote apoptosis in both tumor cells lines and therefore has a prospect for potential use in cancer therapy. PMID- 22079299 TI - High-resolution picture of a venom gland transcriptome: case study with the marine snail Conus consors. AB - Although cone snail venoms have been intensively investigated in the past few decades, little is known about the whole conopeptide and protein content in venom ducts, especially at the transcriptomic level. If most of the previous studies focusing on a limited number of sequences have contributed to a better understanding of conopeptide superfamilies, they did not give access to a complete panorama of a whole venom duct. Additionally, rare transcripts were usually not identified due to sampling effect. This work presents the data and analysis of a large number of sequences obtained from high throughput 454 sequencing technology using venom ducts of Conus consors, an Indo-Pacific living piscivorous cone snail. A total of 213,561 Expressed Sequence Tags (ESTs) with an average read length of 218 base pairs (bp) have been obtained. These reads were assembled into 65,536 contiguous DNA sequences (contigs) then into 5039 clusters. The data revealed 11 conopeptide superfamilies representing a total of 53 new isoforms (full length or nearly full-length sequences). Considerable isoform diversity and major differences in transcription level could be noted between superfamilies. A, O and M superfamilies are the most diverse. The A family isoforms account for more than 70% of the conopeptide cocktail (considering all ESTs before clustering step). In addition to traditional superfamilies and families, minor transcripts including both cysteine free and cysteine-rich peptides could be detected, some of them figuring new clades of conopeptides. Finally, several sets of transcripts corresponding to proteins commonly recruited in venom function could be identified for the first time in cone snail venom duct. This work provides one of the first large-scale EST project for a cone snail venom duct using next-generation sequencing, allowing a detailed overview of the venom duct transcripts. This leads to an expanded definition of the overall cone snail venom duct transcriptomic activity, which goes beyond the cysteine-rich conopeptides. For instance, this study enabled to detect proteins involved in common post-translational maturation and folding, and to reveal compounds classically involved in hemolysis and mechanical penetration of the venom into the prey. Further comparison with proteomic and genomic data will lead to a better understanding of conopeptides diversity and the underlying mechanisms involved in conopeptide evolution. PMID- 22079300 TI - Graphene nanosheets modified glassy carbon electrode for simultaneous detection of heroine, morphine and noscapine. AB - In the present study, the graphene nanosheets (GNSs) modified glassy carbon (GC) electrode is employed for simultaneous determination of morphine, noscapine and heroin. To the best of our knowledge this is the first report of the simultaneous determination of these three important opiate drugs based on their direct electrochemical oxidation. Field emission scanning electron microscopy (FESEM) technique is utilized in order to study the surface morphology of the modified electrode. The modified electrode shows excellent electrocatalytic activity toward oxidation of morphine, noscapine and heroin at reduced overpotentials in wide pH range. In the performed experiments, differential pulse voltammetric determination of morphine, noscapine and heroin yields calibration curves with the following characteristics; linear dynamic range up to 65, 40 and 100 MUM, sensitivity of 275, 500 and 217 nA MUM(-1) cm(-2), and detection limits of 0.4, 0.2 and 0.5 MUM at 3S(B), respectively. Fast response time, signal stability, high sensitivity, low cost and ease of preparation method without using any specific electron-transfer mediator or specific reagent are the advantageous of the proposed sensor. The modified electrode can be used for simultaneous or individual detection of three major narcotic components, heroin, noscapine and morphine at micromolar concentration without any separation or pretreatment steps. PMID- 22079301 TI - Size characterization of the associations between carbon nanotubes and humic acids in aqueous media by asymmetrical flow field-flow fractionation combined with multi-angle light scattering. AB - This work focuses on the influence of humic acids (HAs) on the fate of carbon nanotubes (CNTs) in aqueous media. This influence was demonstrated by mixing CNT powder with HAs in aqueous solution in varying concentrations. The aqueous media containing HAs and CNTs were size-characterized by asymmetrical flow field-flow fractionation (AsFlFFF) coupled with multi-angle light scattering (MALS). This coupling yielded information concerning the size distribution of single- and multi-walled CNTs (SWCNTs and MWCNTs) and HAs under different physico-chemical conditions that can occur in environmental water. HAs can disperse individual CNTs in aqueous media. However, the difference in the physical structure between SWCNTs and MWCNTs leads to significant differences in the quantity of HA that can adsorb onto the nanotube surface and in the stability of the CNT/HA complex. Compared with MWCNTs, SWCNTs suspended in HAs are less affected by changing ionic strength with respect to stability and the amount suspended. PMID- 22079302 TI - Zerovalent iron encapsulated chitosan nanospheres - a novel adsorbent for the removal of total inorganic arsenic from aqueous systems. AB - Evaluation of Chitosan zerovalent Iron Nanoparticle (CIN) towards arsenic removal is presented. Addition of chitosan enhances the stability of Fe(0) nano particle. Prepared adsorbent was characterized by FT-IR, SEM EDX, BET and XRD. It was found that, with an initial dose rate of 0.5 g L(-1), concentrations of As (III) and As (V) were reduced from 2 mg L(-1) to <5 MUg L(-1) in less than 180 min and the adsorbent was found to be applicable in wide range of pH. Langmuir monolayer adsorption capacity was found to be 94+/-1.5 mg g(-1) and 119+/-2.6 mg g(-1) at pH 7 for As (III) and As (V) respectively. Major anions including sulfate, phosphate and silicate did not cause significant interference in the adsorption behavior of both arsenite and arsenate. The adsorbent was successfully recycled five times and applied to the removal of total inorganic arsenic from real life groundwater samples. PMID- 22079303 TI - Parotitis associated with Crimean Congo hemorrhagic fever virus. AB - BACKGROUND: Crimean Congo Hemorrhagic Fever (CCHF) is a potentially fatal tick borne viral disease, the course of which may accompanied by various clinical findings. OBJECTIVES: We describe a picture of non-suppurative parotitis developing in association with CCHF virus. STUDY DESIGN: A 48-year-old patient presenting to our hospital with lethargy, hemorrhage and pain and swelling below the left ear was diagnosed with CCHF through IgM antibody and polymerase chain reaction positivity in serum investigated for CCHF virus. A picture of non suppurative parotitis developed on the 3rd day of admission. RESULTS: Other causes of parotitis were excluded with the help of serological tests, and the case was regarded as one of CCHF-associated parotitis. The patient was put on adjuvant therapy, an improvement in clinical findings was observed and he was discharged in a healthy condition on the 8th day. CONCLUSIONS: Ours is the first case in the literature of parotitis seen during CCHF. CCHF should be considered in differential diagnosis in addition to other frequently encountered viral agents in patients from endemic regions presenting with a picture of non suppurative parotitis. PMID- 22079304 TI - Molecular epidemiology of a large community-based outbreak of hepatitis B in Bristol, U.K. AB - BACKGROUND: A large outbreak of hepatitis B virus (HBV) infection in the U.K. occurred between 2001 and 2005 in Bristol, U.K. OBJECTIVES: To identify HBV strains circulating amongst risk groups in the HBV outbreak cohort. STUDY DESIGN: Cross-sectional study of acute HBV outbreak cases in Bristol. RESULTS: HBV sequences from sera of 95 of the 237 cases (40%) were characterised. The majority of cases (77%) were found to carry an HBV variant belonging to genotype D, designated HBV(BV). Eighty-eight percent (36/41) of sequences from injection drug users were HBV(BV) as were 70% (19/27) from those with heterosexual intercourse as the primary identified risk factor. Of 15 sequences characterised from cases of pre-outbreak acute or chronic hepatitis B residing in Bristol, 40% also carried HBV(BV); the earliest was from a case identified in 1994. CONCLUSION: The findings from this study link the spread of HBV(BV) from injecting drug users to the general population through heterosexual intercourse during the outbreak. The molecular sequencing of specimens from this outbreak reports the emergence of HBV(BV), a HBV strain circulating in Bristol and South West England, as the cause of one of the largest outbreaks of acute hepatitis B in the U.K. PMID- 22079305 TI - Use of real-time polymerase chain reaction (rtPCR) as a diagnostic tool for influenza infection in a vaccine efficacy trial. AB - BACKGROUND: Conventional techniques for diagnosing influenza based on viral cell culture or disease serology have limitations, and molecular assays, such as real time polymerase chain reaction (rtPCR) are increasingly used. OBJECTIVES: To evaluate the use of rtPCR as a diagnostic tool for the determination of influenza virus infection. STUDY DESIGN: This prospective, double-blind, placebo controlled, randomised efficacy study was conducted in persons aged 18-64 years. Cases of influenza-like-illness (ILI), defined as at least one systemic symptom [fever >=37.8 degrees C and/or myalgia] and at least one respiratory symptom [cough and/or sore throat] were identified by active and passive surveillance. For each case of suspected ILI, nasal and throat swabs were collected and analysed by viral culture and rtPCR. RESULTS: 227 ILI cases were positive by rtPCR while 64% (145/227) were positive by both rtPCR and culture. For both assays, the maximum percentage of swabs that tested positive was on Day 0, thereafter positive samples by rtPCR remained constant until Day 5 but decreased progressively by culture. All rtPCR positive cases with a viral load of below 4.5log(10) copies/sample were negative by culture. There were however culture negative cases with high viral loads. Vaccine efficacy for influenza was estimated as 54.7% by rtPCR (culture positive or negative) and 61.6% by culture irrespective of match to vaccine strain. Clinical severity was not significantly different between culture positive cases and culture negative but rtPCR positive cases. CONCLUSIONS: rtPCR is a sensitive and specific diagnostic tool for influenza vaccine efficacy studies. PMID- 22079306 TI - [Multidisciplinary meetings in oncology do not impact the physician-patient relationship]. AB - CONTEXT: The setting of multidisciplinary meeting (MDM) by the French Cancer Plan has introduced new decisional elements in the patient-physician relationship in oncology. METHODS: To assess the potential impact of MDM on this relationship, a study was conducted at the Tours Hospital: 145 questionnaires were collected from patients whose files have been discussed in MDM, 40 questionnaires were collected from physicians attending these meetings and an analysis of 324 files was performed. RESULTS: Patients recognize the decisional process of MDM as reassuring for 80% of them. However, a majority (73%) expressed that the most important for them is the relationship with the referring physician, almost all (96%) having a total or great confidence in him. The results emphasize that trust appears to be related to the quality of communication, open dialogue and the competence of the doctor in particular in the choice of treatment. A review of files shows that in 91% of cases, the opinion of the RCP is applied and that, in 69% of cases, the referring doctor delivers the information to the patient after MDM. From the physicians' perspective, 33/40 report that the MDM do not alter their relationship with the patient. We note that 35/40 express that the consultation after MDM facilitates the presentation of the decision and 37/40 that the decision is always or often applied in accordance with the opinion of the MDM. CONCLUSION: MDM appears in most cases in this study not to modify the patient-physician relationship. Due to the patient confidence into the referring physician, the role of this one is essential in integrating the decisional multidisciplinary opinion of MDM and it is important to ensure from his/her disengagement in the decisional process. PMID- 22079307 TI - [History of robotic surgery in surgery: a progressive evolution towards a surgical revolution]. PMID- 22079308 TI - Predictors of warm ischemia time and perioperative complications in a multicenter, international series of robot-assisted partial nephrectomy. AB - BACKGROUND: Warm ischemia time (WIT) and complication rates are two important parameters for evaluating the perioperative results of robot-assisted partial nephrectomy (RAPN). Few data are available about the clinical predictors of WIT and overall complications. OBJECTIVE: To identify clinical predictors of WIT and perioperative complications. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective study including 347 patients who underwent RAPN for suspicious renal cell carcinoma (RCC) at four referral centers from September 2008 to September 2010. INTERVENTION: All patients underwent RAPN using the da Vinci S Surgical System with hilar clamping. MEASUREMENTS: WIT >20 min and overall complication rates were the main outcomes. Postoperative complications were classified according to the Clavien/Dindo system. Moreover, the following perioperative variables were considered: clinical tumor size, anatomical tumor characteristics according to Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classification score, surgeon experience, console time, blood loss, and upper collecting system (UCS) repair. RESULTS AND LIMITATIONS: WIT >20 min was reported in 125 (36%) cases. Intraoperative and postoperative complications were observed in 10 (2.9%) and 41 (11.8%) cases, respectively. Surgeon experience (odds ratio [OR]: 6.381; 95% confidence interval [CI], 3.687 11.042; p<0.001), clinical tumor size (OR: 1.022; 95% CI, 1.002-1.044; p=0.03), the other anatomic characteristics determined by the PADUA classification score (OR: 1.294; 95% CI, 1.080-1.549; p=0.005), and the UCS repair (OR: 2.987; 95% CI, 1.728-5.165; p<0.001) turned out to be independent predictors of WIT >20 min. Similarly, surgeon experience (OR: 3.937; 95% CI, 2.011-7.705; p<0.001), clinical tumor size (OR: 1.033; 95% CI, 1.009-1.058; p=0.007), and the other anatomical characteristics determined by the PADUA classification score (OR: 1.427; 95% CI, 1.149-1.773; p<0.001) turned out to be independent predictors of overall complication rates. The retrospective design is the main limitation of this multicenter, international study. Therefore, some patient characteristics and comorbidities were not recorded. CONCLUSIONS: Anatomic tumor characteristics as determined by the PADUA classification score were independent predictors of WIT and overall complications, once adjusted for the effects of surgeon experience and clinical tumor size. PMID- 22079309 TI - In vitro evaluation of tectoridin, tectorigenin and tectorigenin sodium sulfonate on antioxidant properties. AB - Tectoridin (4',5,7-thrihydroxy-6-methoxyisoflavone-7-O-beta-d-glucopyranoside) isolated from the flowers of Pueraria thunbergiana is reported to have less hepatoprotective, hypoglycemic, antiallergic and anaphylaxis inhibitory activity than its aglycone form tectorigenin. To obtain tectorigenin, tectoridin was hydrolyzed in the current study. However, practical limitations of tectorigenin do exist due to its poor water-solubility. To increase its water-solubility, tectorigenin was sulfonated with sulfuric acid (98wt.%) and mixed with saturated salt water to produce tectorigenin sodium sulfonate. Tectoridin and the two transfer products were identified by UV, IR, HPLC-MS, (1)H NMR and (13)C NMR, and the solubility of tectorigenin sodium sulfonate was increased about 9-fold than tectorigenin. Antioxidant experiments of tectoridin, tectorigenin and modified tectorigenin in vitro including reducing power, superoxide anion radical scavenging activity, hydroxyl radical scavenging activity, 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity and anti-lipid peroxidation were carried on comparing with ascorbic acid (Vc) or butylated hydroxytoluene (BHT). The results suggested that the antioxidant activity in all the experimental systems exhibited the same order as follows: tectorigenin sodium sulfonate>tectorigenin>tectoridin. Due to the high water-solubility and good antioxidant properties with tectorigenin sodium sulfonate, appropriate chemical modifications could greatly improve the biological activities of the naturally occurring products. PMID- 22079310 TI - Effect on pro-inflammatory and antioxidant genes and bioavailable distribution of whole turmeric vs curcumin: Similar root but different effects. AB - Curcuma longa is a perennial member of the Zingiberaceae family, and cultivated mainly in India, and Southeast Asia. The hypothesis for this study is that turmeric will have distinctive effects from curcumin due to the presence of other bioactive compounds. Thirty Eight-week old Sprague-Dawley rats were separated into three oral feeding groups. Group 1, standard rat chow, Control diet - AIN 93M, group 2 - Curcumin - 700ppm or 0.7g/kg diet, and group 3 - Turmeric - 14,000ppm or 14g/kg diet for a total of 3weeks. One group of rats were feed all three diets only and another group underwent esophagoduodenal anastomosis to evaluate the effects of bioavailability. Curcumin diet did not increase the transcription of mRNA of TNF-alpha, IL-6, iNOS, and COX-2. The average fold change in the mRNAs level was not significant. Whereas turmeric diet increases the levels of IL-6 (1.9-fold, p=0.05), iNOS (4.39-fold, p=0.02), IL-8 (3.11-fold, p=0.04), and COX-2 (2.02-fold, p=0.05), suggesting that turmeric either was more bioavailable or had more affect on pro-inflammatory genes compare to curcumin diet. We have demonstrated the molecular effects of curcumin and turmeric in the role as an anti-inflammatory therapy. However, significant bioavailable differences do occur and must be considered in further chemopreventative investigative trials the setting of reflux esophagitis, Barrett's esophagus, and other upper gastrointestinal cancers. PMID- 22079311 TI - Antioxidant activities of Ganoderma lucidum polysaccharides and their role on DNA damage in mice induced by cobalt-60 gamma-irradiation. AB - In this study, the radio-protective effects of Ganoderma lucidum polysaccharides (GLP) were investigated in a mouse animal model exposed to (60)Co gamma irradiation. Each of three batches of mice were divided into five groups (negative control, positive gamma irradiated control, and low, middle and high dosage GLP groups). Different batches of animals were used to evaluate the impact of GLP on peripheral white blood cell count, immune organ index; DNA damage, lipid peroxidation; micronuclei formation, and nucleated cell count in bone marrow induced by (60)Co gamma-irradiation. DNA strand-break and micronuclei frequency were significantly reduced and glutathione peroxidase activity and nucleated cell count in bone marrow were significantly increased by GLP treatment in a dose-dependent manner. GLP intervention also increased the activity of superoxide dismutase and decreased the level of malondialdehyde in middle and high GLP treatment groups. No adverse effects were observed on peripheral white blood cells and immune organ or body weight in either the control groups or GLP treated gamma exposed mice. These findings suggest that GLP possesses marked antioxidant capacity which plays an important role in the prevention of radiation damage in mice induced by (60)Co gamma-irradiation. PMID- 22079313 TI - Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment. AB - The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content. PMID- 22079312 TI - Cancer chemoprevention by dietary chlorophylls: a 12,000-animal dose-dose matrix biomarker and tumor study. AB - Recent pilot studies found natural chlorophyll (Chl) to inhibit carcinogen uptake and tumorigenesis in rodent and fish models, and to alter uptake and biodistribution of trace (14)C-aflatoxin B1 in human volunteers. The present study extends these promising findings, using a dose-dose matrix design to examine Chl-mediated effects on dibenzo(def,p)chrysene (DBC)-induced DNA adduct formation, tumor incidence, tumor multiplicity, and changes in gene regulation in the trout. The dose-dose matrix design employed an initial 12,360 rainbow trout, which were treated with 0-4000ppm dietary Chl along with 0-225ppm DBC for up to 4weeks. Dietary DBC was found to induce dose-responsive changes in gene expression that were abolished by Chl co-treatment, whereas Chl alone had no effect on the same genes. Chl co-treatment provided a dose-responsive reduction in total DBC-DNA adducts without altering relative adduct intensities along the chromatographic profile. In animals receiving DBC alone, liver tumor incidence (as logit) and tumor multiplicity were linear in DBC dose (as log) up to their maximum-effect dose, and declined thereafter. Chl co-treatment substantially inhibited incidence and multiplicity at DBC doses up to their maximum-effect dose. These results show that Chl concentrations encountered in Chl-rich green vegetables can provide substantial cancer chemoprotection, and suggest that they do so by reducing carcinogen bioavailability. However, at DBC doses above the optima, Chl co-treatments failed to inhibit tumor incidence and significantly enhanced multiplicity. This finding questions the human relevance of chemoprevention studies carried out at high carcinogen doses that are not proven to lie within a linear, or at least monotonic, endpoint dose-response range. PMID- 22079314 TI - Pu-erh black tea extract supplementation attenuates the oxidative DNA damage and oxidative stress in Sprague-Dawley rats with renal dysfunction induced by subchronic 3-methyl-2-quinoxalin benzenevinylketo-1,4-dioxide exposure. AB - 3-Methyl-2-quinoxalin benzenevinylketo-1,4-dioxide (Quinocetone, QCT), has been used to treat dysentery and promote growth in animal feeding. However, available data show that QCT has potential nephrotoxicity. The present study was designed to investigate the protective effects of Pu-erh black tea extract (PBTE) which is a traditional remedy in China with antioxidant properties against oxidative DNA damage and oxidative stress in a rat model of QCT-induced renal dysfunction. Increased serum creatinine, blood urea nitrogen, pathological lesions, urinary 8 hydroxy 2-deoxyguanosine (8-OHdG) and renal DNA damage were observed in the QCT fed rats. These were accompanied by intracellular reactive oxygen species accumulation, enhanced lipid peroxidation, and inhibited antioxidant system, i.e., glutathione glutathione S-transferase, glutathione peroxidase and glutathione reductase. Oral administration of PBTE effectively suppressed QCT induced renal dysfunction, as evidenced by reduced serum creatinine, urinary 8 OHdG and DNA damage in isolated renal cells, amelioration of oxidative stress and modulation of antioxidative system. In conclusion, PBTE administration ameliorated QCT-induced nephrotoxicity by maintaining DNA's double-helix architecture and mitigating oxidative stress. PMID- 22079316 TI - Effects of acute nicotine administration on behavioral and neural (EEG) correlates of working memory in non-smokers. AB - Enhancements in working memory (WM) performance have been previously reported following acute smoking/nicotine. Neuroimaging and behavioral assessments of nicotine's effects on WM have yielded inconsistent findings. Few studies, however, have examined the effects of nicotine on WM-related neural activity in non-smokers. The present study examined the effect of acute nicotine gum administration (6 mg) on electroencephalographic (EEG) activity (alpha(1), alpha(2) and theta bands) and performance on the parametrically manipulated N back task of WM in 20 non-smoking adults. EEG activity varied with WM load (e.g. alpha(1) decreasing and theta increasing). Performance on the N-back was also load-sensitive, with slower reaction times and decreased accuracy associated with increasing memory load. Neither response speed nor accuracy measures were affected by nicotine but EEG was, with the effects varying by load and brain region. Nicotine-induced increases in alpha(2) and theta were observed under lower (0-, 1-back) memory load conditions Additionally, nicotine significantly reduced signal detection sensitivity values and altered response bias toward being more conservative at all levels of the N-back. Taken together, these findings suggest that while nicotine may boost WM neural processes at lower levels of WM load in non-smokers, it also may activate concurrent behavioral inhibition networks that negate any effects on behavioral performance. Additionally, nicotine appears to have no impact, or perhaps a negative impact, on these processes under more demanding (2-back, 3-back) conditions in non smokers. PMID- 22079315 TI - The mechanism of word crowding. AB - Word reading speed in peripheral vision is slower when words are in close proximity of other words (Chung, 2004). This word crowding effect could arise as a consequence of interaction of low-level letter features between words, or the interaction between high-level holistic representations of words. We evaluated these two hypotheses by examining how word crowding changes for five configurations of flanking words: the control condition - flanking words were oriented upright; scrambled - letters in each flanking word were scrambled in order; horizontal-flip - each flanking word was the left-right mirror-image of the original; letter-flip - each letter of the flanking word was the left-right mirror-image of the original; and vertical-flip - each flanking word was the up down mirror-image of the original. The low-level letter feature interaction hypothesis predicts similar word crowding effect for all the different flanker configurations, while the high-level holistic representation hypothesis predicts less word crowding effect for all the alternative flanker conditions, compared with the control condition. We found that oral reading speed for words flanked above and below by other words, measured at 10 degrees eccentricity in the nasal field, showed the same dependence on the vertical separation between the target and its flanking words, for the various flanker configurations. The result was also similar when we rotated the flanking words by 90 degrees to disrupt the periodic vertical pattern, which presumably is the main structure in words. The remarkably similar word crowding effect irrespective of the flanker configurations suggests that word crowding arises as a consequence of interactions of low-level letter features. PMID- 22079317 TI - Genistein inhibits aggregation of exogenous amyloid-beta1-40 and alleviates astrogliosis in the hippocampus of rats. AB - We addressed the question of whether injection of Amyloid beta (Abeta)(1-40) in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Abeta(1-40). Genistein is a plant-derived compound with a structure similar to that of the female sex hormone estrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an (Abeta)(1 40) rat model of Alzheimer's disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Abeta(1-40) positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P<0.0001), CA1 (P=0.03), and CA3 (P=0.002); an increased number of iNOS expressing cells (P=0.01) and gliosis. Genistein given to rats by gavage 1h before injection of Abeta(1-40) inhibited the formation of Abeta(1-40) positive aggregates in the brain tissue and led to increased number of nNOS(+) (P=0.0001) cells in the hippocampus compared to sham-operated genistein-treated controls. Treatment with genistein also alleviated the extensive astrogliosis that occurred in Abeta(1-40)-injected hippocampus to a level similar to that observed in sham operated rats. We conclude that the neurons in the DGlb are most sensitive to Abeta(1-40), and a single dose of genistein can ameliorate Abeta(1-40) induced pathology. PMID- 22079318 TI - Effects of A-CREB, a dominant negative inhibitor of CREB, on the expression of c fos and other immediate early genes in the rat SON during hyperosmotic stimulation in vivo. AB - Intraperitoneal administration of hypertonic saline to the rat supraoptic nucleus (SON) increases the expression of several immediate early genes (IEG) and the vasopressin gene. These increases have usually been attributed to action of the cyclic-AMP Response Element Binding Protein (CREB). In this paper, we study the role of CREB in these events in vivo by delivering a potent dominant-negative form of CREB, known as A-CREB, to the rat SON through the use of an adeno associated viral (AAV) vector. Preliminary experiments on HEK 293 cells in vitro showed that the A-CREB vector that we used completely eliminated CREB-induced c fos expression. We stereotaxically injected this AAV-A-CREB into one SON and a control AAV into the contralateral SON of the same rat. Two weeks following these injections we injected hypertonic saline intraperitoneally into the rat. Using this paradigm, we could measure the relative effects of inhibiting CREB on the induced expression of c-fos, ngfi-a, ngfi-b, and vasopressin genes in the A-CREB AAV injected SON versus the control AAV injected SON in the same rat. We found only a small (20%) decrease of c-fos expression and a 30% decrease of ngfi-b expression in the presence of the A-CREB. There were no significant changes in expression found in the other IEGs nor in vasopressin that were produced by the A CREB. This suggests that CREB may play only a minor role in the expression of IEGs and vasopressin in the osmotically activated SON in vivo. PMID- 22079319 TI - Dose-dependent effects of neonatal SSRI exposure on adult behavior in the rat. AB - Neonatal exposure to antidepressants produces lasting impairments in male sexual behavior. Although perturbation of the serotonin system during neonatal life has been implicated in the long-term behavioral effects of neonatal antidepressant exposure, dose-response studies were necessary to confirm that inhibition of the serotonin transporter during the neonatal period is sufficient to produce impairments in sexual behavior. Therefore, the present study examined the dose response effects of neonatal citalopram exposure on sexual behavior. In addition, the effects of exposure on anxiety-related behavior were examined since alterations in this behavioral measure could affect sexual behavior. Male Long Evans rats were injected subcutaneously with citalopram (CTM) in one of three doses (5, 10 or 20mg/kg/d), or saline (SAL) in a volume of 0.1 ml twice daily (07:00 and 14:00 h) from PD8 to PD21. The rats were tested as adults (>PD90) for anxiety-like behavior and exploration in the elevated plus maze test and sexual behavior. Neonatal citalopram exposure produced persistent reductions in male sexual behavior characterized by significant dose-dependent reductions in the percentage of male rats displaying mounting as well as dose-dependent reductions in the number of mounts and mount latency. Neonatal citalopram exposure also produced significant dose-dependent linear trends for reductions in intromission and ejaculation behavior. However, neonatal SSRI exposure was not found to produce any effects on exploration or anxiety-like behavior in the elevated plus maze test. The present findings support the hypothesis that inhibition of the serotonin transporter during neonatal life by an SSRI is directly responsible for the long-term effects on male sexual behavior. PMID- 22079320 TI - A single administration of methamphetamine to mice early in the light period decreases running wheel activity observed during the dark period. AB - Repeated intermittent administration of amphetamines acutely increases appetitive and consummatory aspects of motivated behaviors as well as general activity and exploratory behavior, including voluntary running wheel activity. Subsequently, if the drug is withdrawn, the frequency of these behaviors decreases, which is thought to be indicative of dysphoric symptoms associated with amphetamine withdrawal. Such decreases may be observed after chronic treatment or even after single drug administrations. In the present study, the effect of acute methamphetamine (METH) on running wheel activity, horizontal locomotion, appetitive behavior (food access), and consummatory behavior (food and water intake) was investigated in mice. A multi-configuration behavior apparatus designed to monitor the five behaviors was developed, where combined measures were recorded simultaneously. In the first experiment, naive male ICR mice showed gradually increasing running wheel activity over three consecutive days after exposure to a running wheel, while mice without a running wheel showed gradually decreasing horizontal locomotion, consistent with running wheel activity being a positively motivated form of natural motor activity. In experiment 2, increased horizontal locomotion and food access, and decreased food intake, were observed for the initial 3h after acute METH challenge. Subsequently, during the dark phase period decreased running wheel activity and horizontal locomotion were observed. The reductions in running wheel activity and horizontal locomotion may be indicative of reduced dopaminergic function, although it remains to be seen if these changes may be more pronounced after more prolonged METH treatments. PMID- 22079321 TI - Developmental changes in the expression of Kappav1 potassium channels in rat vestibular ganglion cells. AB - The primary afferent neurons of the vestibular ganglion convey sensory information from hair cells in the semicircular canals and otolith organs to the vestibular nuclei, the adjacent brainstem and the cerebellum. The intrinsic firing properties of vestibular ganglion cells (VGCs) are heterogeneous and have been classified into phasic, intermediate and tonic firing types on the basis of their response to injected depolarizing currents. A previous study from our group showed that the proportion of phasic discharging VGCs decreased during the first postnatal weeks. Moreover, alpha-dendrotoxin (alpha-DTX), a Kv1 potassium channels antagonist, turned neuron phasic firing to tonic, thus suggesting that these channels play an important role in the developmental changes of VGCs firing patterns. Here, by using immunohistochemistry, Western blotting and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), we explored the change in the expression of alpha-DTX-sensitive K(+) channels, Kv1.1, Kv1.2 and Kv1.6 in rat VGCs during early postnatal periods. We showed that expression of Kv1.6 protein is down-regulated together with expression of Kv1.6 mRNA after postnatal day 7 in rat VGCs whereas expression of Kv1.1 and Kv1.2 proteins did not change during the same developmental period. Our results suggest that down regulation of the Kv1.6 protein and mRNA may be associated with maturation of excitable properties of primary vestibular neurons. PMID- 22079322 TI - Ex vivo detection for chronic ethanol consumption-induced neurochemical changes in rats. AB - The aim of this study was to quantitatively investigate the chronic ethanol induced cerebral metabolic changes in various regions of the rat brain, using the proton high resolution magic angle spinning spectroscopy technique. The rats were divided into two groups (control group: N=11, ethanol-treated group: N=11) and fed with the liquid diets for 10 weeks. In each week, the mean intake volumes of liquid diet were measured. The brain tissues, including cerebellum (Cere), frontal cortex (FC), hippocampus (Hip), occipital cortex (OC) and thalamus (Thal), were harvested immediately after the end of experiments. The ex vivo proton spectra for the five brain regions were acquired with the Carr-Purcell Meiboom-Gill (CPMG) pulse sequence at 500-MHz NMR spectrometer. All of the spectra were processed using the LCModel software, with simulated basis-set file, and the metabolite levels were referenced to total creatine. In the ethanol liquid diet group, there were significant increases in the metabolites ratio levels, as compared to control (Cere: alanine, glutathione, and N acetlyaspartate; FC: phosphocholine and taurine; Hip: alanine, glutamine, and N acetylaspartate; OC: glutamine; Thal: alanine, gamma-aminobutyric acid, glutamate, glycerophosphocholine, phosphocholine, taurine, and free choline). However, in the ethanol liquid diet group, the myo-inositol levels of the OC were significantly lower. The present study demonstrates how chronic ethanol consumption affects cerebral metabolites in the chronic ethanol-treated rat. Therefore, this result could be useful to pursue clinical applications for quantitative diagnosis in human alcoholism. PMID- 22079323 TI - Cortical thickness analysis and optimized voxel-based morphometry in children and adolescents with prelingually profound sensorineural hearing loss. AB - Crossmodal neuroplastic changes following auditory deprivation in individuals with profound sensorineural hearing loss (SNHL) have been well documented in previous literature. However, previous studies have shown very little evidence of structural brain changes in individuals with prelingually profound SNHL and no studies have reported significant differences of gray matter (GM) in deaf subjects. Therefore, it is essential to employ a more specific and sensitive technique to detect subtle structural brain differences in deaf individuals. The objective of our study was to investigate neuroanatomical differences in children and adolescents with profound SNHL by cortical thickness analysis and optimized voxel-based morphometry (VBM). T1-weighted volumetric images of 16 children and adolescents with prelingually profound SNHL and 16 hearing controls were analyzed. The ANCOVA analysis revealed a statistically significant decreased average cortical thickness of the whole brain. As to vertex-based analysis, cortical thickness of the deaf subjects showed significant thinning in the left precentral gyrus, right postcentral gyrus, the left superior occipital gyrus and the left fusiform gyrus compared with the hearing subjects. VBM revealed statistically significant focal reduction of white matter (WM) volume in the left middle frontal gyrus and the right inferior occipital gyrus in deaf subjects without statistically significant differences in GM volume between the two groups. These findings demonstrated that structural changes happened not only in the WM but also in the GM of the subjects with prelingually profound SNHL, which have never been reported before in any previous literature. Our results also implicated the potential neuroplastic changes associated with crossmodal reorganization in the brain after auditory deprivation in the early deafness. PMID- 22079324 TI - Downregulation of miR-199a may play a role in 3-nitropropionic acid induced ischemic tolerance in rat brain. AB - MicroRNAs (miR) are single-stranded short RNA molecules that regulate gene expression by degradation or translational repression of mRNA. It has been reported that the downregulation of miR-199a plays an important role in cardiac ischemic tolerance. We examined the expression of miR-199a after 3-nitropropionic acid (3-NPA) preconditioning in rat brain. 3-NPA (20mg/kg), an irreversible inhibitor of succinate dehydrogenase, was injected intraperitoneally to induce ischemic tolerance in rats. For comparison, the control group received intraperitoneal injections of vehicle (0.9% sodium chloride). Quantitative RT-PCR assay was applied to detect the expression of miR-199a. Luciferase reporter assays and Western blotting were used to verify the target genes of miR-199a. In cortex and striatum, miR-199a was downregulated at two separate time intervals (the 2nd and 4th day), while in the hippocampus, it was downregulated on the 2nd day after 3-NPA preconditioning. The maximum reduction of miR-199a was 66.3% in striatum (4th day), 54.9% in hippocampus (2nd day), and 27.6% in cortex (2nd day). The level of sirt1 protein, a putative target of miR-199a and a known mediator of neuroprotective effect in brain ischemic tolerance, decreased significantly in hippocampal neurons by overexpression of miR-199a, while it increased with knockdown of miR-199a. Taking these results together, we hypothesize miR-199a may have a role in the formation of cerebral ischemic tolerance. PMID- 22079325 TI - Increased expression of placental growth factor in patients with temporal lobe epilepsy and a rat model. AB - Placental growth factor (PIGF) plays a role in angiogenesis and neuroprotection. It has been suggested that angiogenesis and blood-brain barrier damage are involved in the pathophysiology of epilepsy. In this study, we investigated the PIGF expression in the temporal neocortices of 11 patients with pharmaco resistant temporal lobe epilepsy (TLE) and 6 non-epileptic controls, using double immunofluorescence labeling, immunohistochemistry and Western blotting. We also assessed PIGF expression pattern in a rat model of TLE induced by lithium chloride-pilocarpine. We found that PIGF expression was significantly elevated in patients with TLE than in control. TLE patients with initial injuries had significantly higher PIGF level than those without initial injuries. In the TLE rat model, PIGF upregulation started at 6h after status epilepticus and maintained at significant high level for up to 60 days. These results suggest that the augmentation of brain PIGF is associated with development of epilepsy. PMID- 22079326 TI - The ratio of phosphatidylcholine to phosphatidylethanolamine does not predict integrity of growing MT58 Chinese hamster ovary cells. AB - Phosphatidylcholine (PC) homeostasis is important for maintaining cellular growth and survival. Cellular growth and apoptosis may also be influenced by the PC to phosphatidylethanolamine (PE) ratio as a reduction in this ratio can result in a loss of membrane integrity. To investigate whether a reduced PC:PE ratio influences cellular growth and apoptosis, we utilized the MT58 cell line, which contains a thermo-sensitive mutation in CTP:phosphocholine cytidylyltransferase alpha, the rate-limiting enzyme for PC biosynthesis. Incubation of MT58 cells at the restrictive temperature of 41 degrees C results in a reduction of cellular PC and induces apoptosis. Furthermore, MT58 cells have a 50% reduction in the PC:PE ratio when incubated at 41 degrees C. In an attempt to normalize the PC:PE ratio, which may stabilize cellular membranes and rescue MT58 cells from apoptosis, the cells were treated with either silencing RNA to impair PE biosynthesis or lysophosphatidylcholine to increase PC mass. Impairing PE biosynthesis in MT58 cells reduced cellular PE and PC concentrations by 30% and 20%, but did not normalize the PC:PE ratio. Loss of both phospholipids enhanced the onset of apoptosis in MT58 cells. Lysophosphatidylcholine normalized cellular PC, increased PE mass by 10%, restored cellular growth and prevented apoptosis of MT58 cells without normalizing the PC:PE ratio. Furthermore, total amount of cellular PC and PE, but not the PC:PE ratio, correlated with cellular growth (R(2)=0.76), and inversely with cellular apoptosis (R(2)=0.97). These data suggest the total cellular amount of PC and PE, not the PC:PE ratio, influences growth and membrane integrity of MT58 cells. PMID- 22079327 TI - How to recognise collateral damage in partial nerve injury models of neuropathic pain. PMID- 22079329 TI - CETP inhibition in perspective. PMID- 22079328 TI - The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. AB - CONTEXT: Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration and, usually, death during childhood. There has been no recent comprehensive analysis of the natural history and clinical course of this disease. OBJECTIVE: We reviewed 371 cases of PDC deficiency, published between 1970 and 2010, that involved defects in subunits E1alpha and E1beta and components E1, E2, E3 and the E3 binding protein of the complex. DATA SOURCES AND EXTRACTION: English language peer-reviewed publications were identified, primarily by using PubMed and Google Scholar search engines. RESULTS: Neurodevelopmental delay and hypotonia were the commonest clinical signs of PDC deficiency. Structural brain abnormalities frequently included ventriculomegaly, dysgenesis of the corpus callosum and neuroimaging findings typical of Leigh syndrome. Neither gender nor any clinical or neuroimaging feature differentiated the various biochemical etiologies of the disease. Patients who died were younger, presented clinically earlier and had higher blood lactate levels and lower residual enzyme activities than subjects who were still alive at the time of reporting. Survival bore no relationship to the underlying biochemical or genetic abnormality or to gender. CONCLUSIONS: Although the clinical spectrum of PDC deficiency is broad, the dominant clinical phenotype includes presentation during the first year of life; neurological and neuromuscular degeneration; structural lesions revealed by neuroimaging; lactic acidosis and a blood lactate:pyruvate ratio <=20. PMID- 22079330 TI - Development of IgA nephropathy-like glomerulonephritis associated with Wiskott Aldrich syndrome protein deficiency. AB - Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder caused by mutations in the WAS gene. Glomerulonephritis is a frequent complication, however, histopathological data from affected patients is scarce because the thrombocytopenia that affects most patients is a contraindication to renal biopsies. We found that WASp-deficient mice develop proliferative glomerulonephritis reminiscent of human IgA nephropathy (IgAN). We examined whether increased aberrant IgA production is associated with the development of glomerulonephritis in WASp-deficient mice. Serum IgA and IgA production by splenic B cells was increased in WASp-deficient mice compared to wild-type (WT) mice. A lectin-binding study revealed a reduced ratio of sialylated and galactosylated IgA in the sera from old WASp-deficient mice. Circulating IgA containing immune complexes showed significantly higher titers in WASp-deficient mice compared to WT mice. These results indicate that the increased IgA production and aberrant glycosylation of IgA may be critically involved in the pathogenesis of glomerulonephritis in WAS. PMID- 22079331 TI - Targeted immunosuppression: no longer naive. PMID- 22079332 TI - Patterns of estrous cycles, estrous behavior, and circulating prolactin in spring and summer in ewes selected for autumn lambing and exposed to ambient or long-day photoperiods. AB - Estrous behavior in response to ambient and long-day photoperiods was evaluated in ewes developed by 10 years of selection for ability to lamb in autumn. Following October lambing, 67 ewes were moved indoors and exposed to long-day (16L:8D) or ambient photoperiods from February 2 until July 6. Two vasectomized rams with marking harnesses were housed with each group. Estrous behavior was monitored twice weekly. Ewes from the selection line were unresponsive to long days, with no effects on estrous behavior, frequency of ovulation, or circulating prolactin. Adult ewes were anestrus for only 34+/-3 d, but 2- and 3-years-old ewes were anestrus for 72+/-7 and 57+/-10 d, respectively. Frequencies of ovulation based on circulating progesterone concentrations in March, May, and June were 97%, 95% and 52%, respectively, indicating that many ewes that did not exhibit estrus still ovulated. Prolactin concentrations increased from 10 ng/ml in February to 27 ng/ml in March and 173 ng/ml in June but were not affected by light treatment. Ten ewes that failed to exhibit estrus behavior for at most 24 d during the main study were then monitored for 74 additional long days. Nine of 10 ewes did not exhibit estrus for periods similar to 1 or 2 estrus cycles during this period, but eight ewes re-initiated cycles by the end of the study on September 18. Selection for ability to lamb in autumn thus resulted in ewes with an abbreviated seasonal anestrus and reduced sensitivity to long days. PMID- 22079333 TI - [The social value of informal care provided to elderly dependent people in Spain]. AB - OBJECTIVE: To analyze one part of the social benefit derived from non professional (informal) caregivers by analyzing the hypothetical amount of resources that would need to be invested if informal care were substituted by formal care. METHODS AND DATA: Using data from the Survey of Disabilities, Personal Autonomy and Situations of Dependency (EDAD-2008), we estimated the cost to society if informal care were substituted by formal care of the population aged 65 years and older. For this purpose, first we computed the total amount of informal caregiving hours provided in Spain in 2008, and then we obtained its monetary worth by using the proxy good method. RESULTS: The monetary worth of informal care provided in 2008 ranged from 25,000 and 40,000 million euros, depending on the shadow price used to value one hour of care. These figures represented between 2.3% and 3.8% of the GDP for the same year. In regional terms, the valuation of informal care across Spain's autonomous regions showed a significant degree of dispersion, and in some regions, amounted to 6% of their GDP. CONCLUSIONS: The comprehensive approach to the care of the elderly should take the role and needs of informal caregivers into consideration. Caregivers should be given greater social recognition. PMID- 22079334 TI - IL-33 enhances Siglec-8 mediated apoptosis of human eosinophils. AB - IL-33 activates eosinophils directly via the ST2 receptor. Like IL-5, IL-33 induces eosinophilia and eosinophilic airway inflammation in mouse models and primes human eosinophil responses. Previously, we reported that IL-5 priming enhances Siglec-8 mediated mitochondrial and reactive oxygen species (ROS) dependent eosinophilic apoptosis and eliminates caspase dependence of this cell death process. Whether IL-33, like IL-5, augments pro-apoptotic pathways involving receptors such as Siglec-8 and in a similar manner has not been explored. Annexin-V labeling was performed to detect apoptosis in human eosinophils pre-incubated with or without a range of concentrations of IL-33 and/or IL-5 in the presence or absence of Siglec-8 monoclonal antibody (mAb) 2C4 and inhibitors of caspases. Tetramethyl-rhodamine staining was used as a marker of mitochondrial membrane potential loss and injury. ROS production was determined by measuring the superoxide dismutase-inhibitable reduction of cytochrome c. Cleavage of poly(ADP-ribose) polymerase (PARP) was assessed using Western blotting. Eosinophils cultured alone or with mAb 2C4 underwent low levels of apoptosis at 24h. 2C4-induced eosinophil apoptosis was markedly and equally enhanced after culture for 24h with either IL-33 or IL-5, although IL-5 was more potent. Effects on apoptosis with IL-33 and IL-5 were synergistic. In contrast, percentages of cells exhibiting reduced mitochondrial membrane potential were greater with IL-33 than IL-5 and effects of these cytokines were also synergistic. Antimycin, an inhibitor of mitochondrial electron transport, almost completely inhibited 2C4-induced apoptosis with either IL-33 or IL-5. Surprisingly, 2C4-induced eosinophil ROS production was significantly enhanced with IL-5 but not IL-33. Siglec-8-mediated apoptosis in the presence of IL-33 was more sensitive in magnitude than IL-5 to inhibition by the pan-caspase inhibitor Z-VAD-FMK, yet both cytokine conditions were associated with PARP cleavage. These data demonstrate that IL-33 is as effective but less potent than IL-5 in enhancing Siglec-8-mediated eosinophil apoptosis, and can synergize with IL-5. Eosinophils primed by IL-33 and/or IL-5 in vivo would be expected to display enhanced susceptibility to undergoing Siglec-8-induced apoptosis. PMID- 22079335 TI - Hematopoiesis sculpted by pathogens: Toll-like receptors and inflammatory mediators directly activate stem cells. AB - Hematopoietic stem cells (HSCs) repopulate the immune system during normal replenishment as well as under the burden of pathogen stress, but the respective outcomes of differentiation are not the same. Under homeostatic conditions such as those which accompany turnover of immune cell subsets, HSCs appear to co equally prime genes associated with the major downstream lineages: lymphoid, myeloid, and megakaryocyte/erythroid. Recent studies reveal, however, that during pathogen exposure, hematopoiesis may yield progeny in proportions different than those produced under homeostasis. At least some of these effects may be due to pathogen engagement of Toll-like receptors (TLRs) expressed on HSCs. HSCs are also responsive to inflammatory cytokines that are produced in response to pathogen burden and are present in the bone marrow microenvironment. Thus, hematopoiesis is not a formulaic process that produces the same, predictable outcome regardless of the specific environmental context. Rather, hematopoiesis represents a dynamic biological system that can be appreciably responsive to environmental factors, an influence that extends to the level of the HSC itself. Knowledge of functional consequences of TLR ligation on HSCs may be therapeutically exploited and applied to treatment of hematopoietic insufficiency in the setting of infection and disease. PMID- 22079336 TI - Point-to-point registration with mandibulo-maxillary splint in open and closed jaw position. Evaluation of registration accuracy for computer-aided surgery of the mandible. AB - INTRODUCTION: Computer navigation plays an increasingly important role in craniomaxillofacial surgery. The difficulties in computer navigation at the craniomaxillofacial site lie in the accurate transmission of the dataset to the operating room. This study investigates the accuracy of the dental-splint registration method for the skull, midface, and mandible. MATERIAL AND METHODS: A synthetic human skull model was prepared with landmarks and scanned with cone beam computer tomography (CBCT). Two registration splints fixed the mandible against the viscerocranium in two different positions (closed vs. open). The target registration error was computed in all 278 landmarks spread over the entire skull and mandible in 10 repeated measurements using the VectorVision(2) (BrainLAB Inc., Feldkirchen, Germany) navigation system. RESULTS: If registered in the closed position an average precision of 2.07 mm with a standard deviation (SD) of 0.78 mm was computed for all landmarks distributed over the whole skull. Registration in the open position resulted in an average precision of 1.53 mm (SD=0.55 mm). For single landmarks the precision decreases linearly with distance from the reference markers. The longer the three-dimensional distance between the registration points, the more precise the computer navigation is, mainly in the most posterior area of the cranium. CONCLUSION: Our findings in the cranium are comparable with those of other studies. Artificial fixation of the lower jaw via splint seems to introduce no additional error. The registration points should be as far apart from each other as possible during navigation with the splint. PMID- 22079337 TI - A fast and accurate automatic lung segmentation and volumetry method for MR data used in epidemiological studies. AB - In modern epidemiological population-based studies a huge amount of magnetic resonance imaging (MRI) data is analysed. This requires reliable automatic methods for organ extraction. In the current paper, we propose a fast and accurate automatic method for lung segmentation and volumetry. Our approach follows a "coarse-to-fine" segmentation strategy. First, we extract the lungs and trachea excluding the main pulmonary vessels. This step is executed very fast and allows for measuring the volume of both structures. Thereafter, we start a refinement procedure that consists of three main stages: trachea extraction, lung separation, and filling the cavities on the final lung masks. After the trachea extraction step the volumes of both lungs without the main vessels can be measured. The final segmentation step results in the volumes of the left and right lungs including the vessels. The method has been tested by processing MR datasets from ten healthy participants. We compare our results with manually produced masks and obtain high agreement between the expert reading and our method: the True Positive Volume Fraction is more than 95%. The proposed automatic approach is fast and accurate enough to be applied in clinical routine for processing of thousands of participants. PMID- 22079338 TI - Mean platelet volume (MPV) is associated with leukoaraiosis in the apparently healthy elderly. AB - Leukoaraiosis refers to diffuse white matter abnormalities on MR brain scans, which have been suggested to be associated with cerebral microangiopathy and geriatric syndromes such as cognitive impairment, depressive mood and gait disturbance. MPV is a simple indicator of platelet size and has been known to be a marker of platelet activity. MPV is now considered a link between inflammation and thrombosis in multiple cardiovascular and cerebrovascular disorders including hypertension, peripheral artery disease, and stroke. This cross-sectional study aims to evaluate the association between MPV and leukoaraiosis for 223 healthy elderly subjects (142 men, 81 women; mean age 66.0+/-5.2 years) in a health examination program including brain magnetic resonance imaging (MRI) scans. The overall prevalence rate of leukoaraiosis was 15.3%. The mean MPV was significantly higher in the leukoaraiosis group than control group: 8.4+/-0.8 and 8.1+/-1.0, respectively (p=0.036). A higher value of MPV was independently associated with an increased risk of leukoaraiosis. In the multivariate logistic analysis, the odds ratio (OR) (95% confidence interval (CI)) for leukoaraiosis was 1.61 (1.02-2.53) with 1 fL of MPV increment after adjusting for confounding variables. In conclusion, MPV was found to be independently and positively associated with leukoaraiosis. This finding indicates that MPV values may be a useful additional measure in assessing the risk of leukoaraiosis in the clinical setting. PMID- 22079339 TI - Mapping of the binding sites for the OX1 orexin receptor antagonist, SB-334867, using orexin/hypocretin receptor chimaeras. AB - The binding sites for agonists and antagonist of orexin receptors are not know, hampering progressive drug design approaches. In the current study, we utilized chimaeric orexin receptor approach to map the receptor areas contributing to the selectivity of the classical antagonist, SB-334867, for OX(1) receptors. Altogether ten chimaeras between OX(1) and OX(2) orexin receptors were utilized. The receptors were transiently expressed in HEK-293 cells. The ability (K(B)) of SB-334867 to inhibit orexin-A-induced inositol phosphate release (phospholipase C activity) was measured. The results, in synthesis, suggest that there are several possible interactions contributing to the high affinity binding, all of which are not required simultaneously. This is indicated by the fact that most of the chimaeras display affinity (at least somewhat) higher than OX(2). As previously shown for the agonist distinction, the second quarter of the receptor, from the C terminal part of the transmembrane helix 2 to the transmembrane helix 4 seems to be most central also for SB-334867 binding, but also the third quarter, from the transmembrane helix 4 to the transmembrane helix 6 is able to contribute (and compensate for loss of other sites). A previous study has suggested that amino acids conserved between OX(1) and OX(2) receptors would somehow confer selectivity for subtype-selective antagonists. In contrast to previous findings, our results indicate that the amino acids distinct between the receptor subtypes are in key position. PMID- 22079340 TI - Multi-organ investigation in 16 CADASIL families from central Italy sharing the same R1006C mutation. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may involve many target organs with relevant variability among affected individuals. We performed a multi-organ assessment tapping nervous system, skeletal muscle and cardiovascular system in thirty-nine individuals belonging to 16 families from Central Italy sharing the same R1006C CADASIL mutation. Stroke prevalence was larger in female patients (66.7%) than in males (23.8%); high levels of CKemia were quite frequent (21.6%) and were related to a myopathy without mitochondrial alterations; several individuals had atrial septal aneurysm (10.3%). No specific relationships between common cardiovascular risk factors and clinical manifestations were found. The present systematic study thus identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. This kind of comprehensive approach is necessary to define clinical course, prognosis and treatment options for a multi organ disease such as CADASIL. PMID- 22079341 TI - Investigation of the mechanisms of progesterone protection following oxygen glucose deprivation in organotypic hippocampal slice cultures. AB - This study aimed to test the hypothesis that progesterone is neuroprotective against oxygen-glucose deprivation (OGD) through its conversion to the active metabolite allopregnanolone (AlloP) and the potentiation of GABA(A) receptors. Organotypic hippocampal cultures were exposed to 2h of OGD and the resulting cell death was quantified 24h later using combined propidium iodide and Hoechst immunostaining. Initially, we confirmed, that both progesterone and AlloP were protective in terms of reducing cell death following OGD in hippocampal cultures and for both, the optimal level of protection was observed at a concentration of 0.1MUM. However, the protective effect of progesterone was absent in the presence of finasteride (10MUM) which inhibits the metabolism of progesterone to active metabolites, including AlloP. In addition, the concurrent application of picrotoxin (100MUM), a potent GABA(A) receptor antagonist, prevented the protection previously seen by either progesterone or AlloP alone. These results indicate that progesterone protects hippocampal cultures from cell death following OGD largely due to its conversion to AlloP and that GABA(A) receptors are important mediators of the protective effects of both progesterone and AlloP. PMID- 22079342 TI - Cervical dermoid sinus in a cat: case presentation and review of the literature. AB - A 6-month-old female spayed domestic shorthair cat was presented for evaluation of a focal subcutaneous swelling on the dorsal neck at the level of atlas. The magnetic resonance imaging and surgical treatment of a dermoid sinus associated with the cervical vertebrae is described. To the authors' knowledge, a dermoid sinus in this location has not been described previously in the cat. The prognosis following surgical resection appears favorable. PMID- 22079343 TI - Mycobacterial disease in cats in Great Britain: I. Culture results, geographical distribution and clinical presentation of 339 cases. AB - This study investigated 339 cases of feline mycobacterial disease from cats with cutaneous lesions or masses found at exploratory laparotomy. Tissue samples were submitted to the Veterinary Laboratories Agency for mycobacterial culture over a 4-year period to December 2008. The study assessed which species of culturable mycobacteria were involved, where the cats lived, and their clinical presentation (physical findings, serum biochemistry, radiography, feline leukaemia virus and feline immunodeficiency virus status). Mycobacterium microti was cultured from 19%, Mycobacterium bovis 15%, Mycobacterium avium 7%, non-M avium non-tuberculous mycobacteria 6%, with no growth in 53% of samples. M microti, M bovis and M avium were found in almost mutually exclusive clusters within Great Britain (GB) (ie, M bovis in South-West England/Wales/Welsh Border, M avium in eastern England and M microti south of London and in South-West Scotland). While differences were seen in the clinical presentation and distribution of lesions caused by the different infections, these were not sufficiently different to be diagnostic. Cats commonly presented with single or multiple cutaneous lesions (74%), which were sometimes ulcerated or discharging, located most frequently on the head (54%). Lymph nodes were usually involved (47%); typically the submandibular nodes. Systemic or pulmonary signs were rarely seen (10-16%). When a cat is suspected of having mycobacteriosis, accurate identification of the species involved helps to determine appropriate action. Our findings show that knowing the cat's geographic location can be helpful, while the nature of the clinical presentation is less useful. Most cases of feline mycobacterial disease in GB are cutaneous. PMID- 22079345 TI - Effect of remote ischemic conditioning on dendritic cell number in blood after renal transplantation--flow cytometry in a porcine model. AB - Delayed graft function after transplantation increases the risk of rejection. Remote ischemic conditioning (rIC) consists of repetitive, brief, non-damaging periods of ischemia in a limb. For reasons not fully understood, rIC protects the target organ against subsequent ischemia-reperfusion injury. Because ischemic endothelium attracts dendritic cells (DCs), we hypothesised that rIC protects the organ by "trapping" circulating DCs in the limb exposed to rIC. With fewer DCs thus available to infiltrate the graft, a strong T-cell mediated immune response toward the graft is less likely. To test this hypothesis, we measured the number of circulating DCs in a porcine model of renal transplantation with and without rIC. Brain death was induced in eight 65-kg donor pigs. After 22 h of cold ischemia, the kidneys were transplanted into sixteen 15-kg recipient pigs. The recipients were randomised to either non-rIC or rIC before reperfusion of the graft and observed 10 h after reperfusion. The number of DCs was determined by flow cytometry. DCs were identified on the basis of forward- and side-scatter characteristics of CD14-negative mononuclear cells with expression of CD172a. Dendritic cells were subclassified as either plasmacytoid (pDCs) (CD172a(dim), CD4(+), CD14(-)) or conventional (cDCs) (CD172a(high), CD4(-), CD14(-)). Remote ischemic conditioning did not affect the number of circulating cDCs or pDCs within the 10h after transplantation studied. Regardless of rIC, the number of pDCs decreased after graft reperfusion and then returned to baseline levels. In contrast, the number of circulating cDCs increased after reperfusion and later returned to baseline levels. PMID- 22079344 TI - The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 (ALDH1A2 and ALDH2) is detected by Aldefluor, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance. AB - There has been a new interest in using aldehyde dehydrogenase (ALDH) activity as one marker for stem cells since the Aldefluor flow cytometry-based assay has become available. Diethylaminobenzaldehyde (DEAB), used in the Aldeflour assay, has been considered a specific inhibitor for ALDH1A1 isoform. In this study, we explore the effects of human ALDH isoenzymes, ALDH1A2 and ALDH2, on drug resistance and proliferation, and the specificity of DEAB as an inhibitor. We also screened for the expression of 19 ALDH isoenzymes in K562 cells using TaqMan Low Density Array (TLDA). We used lentiviral vectors containing the full cDNA length of either ALDH2 or ALDH1A2 to over express the enzymes in K562 leukemia and H1299 lung cancer cell lines. Successful expression was measured by activity assay, Western blot, RT-PCR, and Aldefluor assay. Both cell lines, with either ALDH1A2 or ALDH2, exhibited higher cell proliferation rates, higher clonal efficiency, and increased drug resistance to 4-hydroperoxycyclophosphamide and doxorubicin. In order to study the specificity of known ALDH activity inhibitors, DEAB and disulfiram, we incubated each cell line with either inhibitor and measured the remaining ALDH enzymatic activity. Both inhibitors reduced ALDH activity of both isoenzymes by 65-90%. Furthermore, our TLDA results revealed that ALDH1, ALDH7, ALDH3 and ALDH8 are expressed in K562 cells. We conclude that DEAB is not a specific inhibitor for ALDH1A1 and that Aldefluor assay is not specific for ALDH1A1 activity. In addition, other ALDH isoenzymes seem to play a major role in the biology and drug resistance of various malignant cells. PMID- 22079346 TI - Exercise-induced galanin release facilitated GLUT4 translocation in adipocytes of type 2 diabetic rats. AB - Although galanin has been shown to increase insulin sensitivity in skeletal muscle of rats, there is no literature available about the effect of galanin on Glucose Transporter 4 (GLUT4) translocation from intracellular membrane pools to plasma membranes in adipocytes of type 2 diabetic rats. In the present study M35, a galanin antagonist was used to elucidate whether exercise-induced galanin release increased GLUT4 translocation in adipocytes of streptozotocin-induced diabetic rats. The present findings showed that plasma galanin levels after swimming training in all four trained groups were higher compared with each sedentary control. M35 treatment had an inhibitory effect on glucose infusion rates in the euglycemic-hyperinsulinemic clamp test and GLUT4 mRNA expression levels in adipocytes. Moreover, M35 treatment reduced GLUT4 concentration in both plasma membranes and total cell membranes. The ratios of GLUT4 contents in plasma membranes to total cell membranes in four drug groups were lower compared with each control. These data demonstrate a beneficial role of endogenous galanin to transfer GLUT4 from internal stores to plasma membranes in adipocytes of type 2 diabetic rats. Galanin plays a significant role in regulation of glucose metabolic homeostasis and is an important hormone relative to diabetes. PMID- 22079347 TI - Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1. AB - The trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that is functionally activated by amphetamine-based psychostimulants, including amphetamine, methamphetamine and MDMA. Previous studies have shown that in transgenic mice lacking the TAAR1 gene (TAAR1 knockout; KO) a single injection of amphetamine can produce enhanced behavioral responses compared to responses evoked in wild-type (WT) mice. Further, the psychostimulant effects of cocaine can be diminished by selective activation of TAAR1. These findings suggest that TAAR1 might be implicated in the rewarding properties of psychostimulants. To investigate the role of TAAR1 in the rewarding effects of drugs of abuse, the psychomotor stimulating effects of amphetamine and methamphetamine and the conditioned rewarding effects of methamphetamine and morphine were compared between WT and TAAR1 KO mice. In locomotor activity studies, both single and repeated exposure to d-amphetamine or methamphetamine generated significantly higher levels of total distance traveled in TAAR1 KO mice compared to WT mice. In conditioned place preference (CPP) studies, TAAR1 KO mice acquired methamphetamine-induced CPP earlier than WT mice and retained CPP longer during extinction training. In morphine-induced CPP, both WT and KO genotypes displayed similar levels of CPP. Results from locomotor activity studies suggest that TAAR1 may have a modulatory role in the behavioral sensitization to amphetamine-based psychostimulants. That methamphetamine-but not morphine-induced CPP was augmented in TAAR1 KO mice suggests a selective role of TAAR1 in the conditioned reinforcing effects of methamphetamine. Collectively, these findings provide support for a regulatory role of TAAR1 in methamphetamine signaling. PMID- 22079348 TI - Tolerance to cocaine's effects on schedule-controlled behavior: role of delay between pause-ending responses and reinforcement. AB - The schedule of reinforcement under which behavior is maintained is an important contributor to whether tolerance to the behavioral effects of cocaine develops. Schedule parameter value (for example, fixed-ratio size) has been shown to affect the development of tolerance under some schedule types but not others, but the specific procedural variables causing this effect remain to be identified. To date, schedule-parameter-related tolerance has developed when a longer pause after reinforcement does not lead to a shorter delay between the response that ends the pause and reinforcement. The current study investigated the importance of this variable in pigeons using a multiple chained Fixed-Ratio 1, Fixed-Time x schedule, in which the first key peck in a trial produced a stimulus change and initiated a delay at the end of which food was presented regardless of whether or not additional pecks were made during the delay. Dose-response curves were assessed before, during and after chronic (daily) administration of cocaine. Tolerance to the pause-increasing effects of cocaine occurred to a similar degree regardless of the scheduled time between the end of the pause and reinforcement. Therefore, the relationship between pause length and delay to reinforcement does not provide an explanation for schedule-parameter-related tolerance. PMID- 22079349 TI - Anaplastic lymphoma kinase and leukocyte tyrosine kinase: functions and genetic interactions in learning, memory and adult neurogenesis. AB - Anaplastic Lymphoma Kinase (Alk) is a receptor tyrosine kinase expressed throughout the adult mammalian hippocampus. Recent studies in Drosophila and prior studies in Caenorhabditis elegans have implicated Alk signaling in learning and neurogenesis. We have studied the roles of Alk and the closely related receptor Leukocyte Tyrosine Kinase (Ltk) in learning, behavior and neurogenesis. In the hippocampus, both receptors are expressed throughout the dentate gyrus, CA1 and CA3. To assess the functional roles of Alk and Ltk in the mammalian brain, we analyzed phenotypes in Alk mutant, Ltk mutant and Alk/Ltk double-mutant mice compared to wild-type littermates. Similar to Drosophila, we found enhanced performance in spatial memory in Alk mutant mice. Also similar to Drosophila, we observed reduced neurogenesis associated with loss of Alk function. We also report genetic interactions between Alk and Ltk with respect to neurogenesis and behavioral measures such as activity, anxiety levels, and retention of spatial memory. PMID- 22079350 TI - Mechanical analysis of Drosophila indirect flight and jump muscles. AB - The genetic advantages of Drosophila make it a very appealing choice for investigating muscle development, muscle physiology and muscle protein structure and function. To take full advantage of this model organism, it has been vital to develop isolated Drosophila muscle preparations that can be mechanically evaluated. We describe techniques to isolate, prepare and mechanically analyze skinned muscle fibers from two Drosophila muscle types, the indirect flight muscle and the jump muscle. The function of the indirect flight muscle is similar to vertebrate cardiac muscle, to generate power in an oscillatory manner. The indirect flight muscle is ideal for evaluating the influence of protein mutations on muscle and cross-bridge stiffness, oscillatory power, and deriving cross bridge rate constants. Jump muscle physiology and structure are more similar to skeletal vertebrate muscle than indirect flight muscle, and it is ideal for measuring maximum shortening velocity, force-velocity characteristics and steady state power generation. PMID- 22079351 TI - New trends in fluorescence in situ hybridization for identification and functional analyses of microbes. AB - Fluorescence in situ hybridization (FISH) has become an indispensable tool for rapid and direct single-cell identification of microbes by detecting signature regions in their rRNA molecules. Recent advances in this field include new web based tools for assisting probe design and optimization of experimental conditions, easy-to-implement signal amplification strategies, innovative multiplexing approaches, and the combination of FISH with transmission electron microscopy or extracellular staining techniques. Further emerging developments focus on sorting FISH-identified cells for subsequent single-cell genomics and on the direct detection of specific genes within single microbial cells by advanced FISH techniques employing various strategies for massive signal amplification. PMID- 22079352 TI - Clostridia: the importance of their exceptional substrate and metabolite diversity for biofuel and biorefinery applications. AB - Clostridia are anaerobic Firmicutes producing a large array of metabolites by utilizing simple and complex carbohydrates, such as cellulose, as well as CO2/H2 or CO. Their exceptional substrate diversity is enhanced by their ability to produce a broad spectrum of chemicals that can be used as precursors to or directly as biofuels and industrial chemicals. Genetic and genomic tools are under intense development, and recent efforts to metabolically engineer clostridia demonstrate their potential for biofuel and biorefinery applications. Pathway engineering to combine established substrate-utilization programs, such as for cellulose, CO2/H2 or CO, with desirable metabolic programs could lead to modular design of strains suitable for many applications. Engineering complex phenotypes--aerotolerance, abolished sporulation, and tolerance to toxic chemicals--could lead to superior bioprocessing strains. PMID- 22079353 TI - Low energy microcolumn for large field view inspection. AB - Since the development of microcolumn system, it attracted much attention because multiple microcolumns can be assembled into arrayed form, which is expected to generate multiple electron beams and overcome the disadvantage of electron beam inspection equipments, low throughput. However, it is not easy to apply a microcolumn to the practical inspection or testing equipment since its scanning area is too small. Even if the arrayed operation using multiple microcolumns can overcome this limit, it requires complicated supporting systems and related technologies to operate a number of microcolumns simultaneously. Therefore, we tried to modify microcolumn design itself so that it can have a large field of view. In this work, two kinds of modified columns will be suggested and the preliminary results showing their performance of scanning large area will be discussed. PMID- 22079354 TI - Large cell neuroendocrine carcinoma arising in a sessile serrated adenoma: a novel observation. AB - A 68-year-old woman underwent polypectomy of 2 right-sided colonic polyps identified by screening colonoscopy. Histologic examination of both polyps showed features of sessile serrated adenoma. The larger polyp harbored an invasive tumor composed of large, high-grade cells arranged in nests and cords without tumoral mucin production. Immunohistochemistry demonstrated synaptophysin, cdx-2, cytokeratin 7, and cytokeratin 20 positivity. Both invasive carcinoma and sessile serrated adenoma showed a decreased expression level to focal negative expression of hMLH-1 by immunohistochemistry. Combined morphologic and immunohistochemical features favored large cell neuroendocrine carcinoma arising in a sessile serrated adenoma. Specific carcinoma subtypes and special histologic features (eg, tumor-infiltrating lymphocytes) have been previously reported in carcinomas arising from sessile serrated adenomas. Large cell neuroendocrine carcinoma has not yet been reported in association with sessile serrated adenomas, with this case suggesting a rare but potentially novel end point for the microsatellite instability pathway. PMID- 22079355 TI - Composition and significance of splenic Gamna-Gandy bodies in sickle cell anemia. AB - Children with sickle cell anemia may undergo acute splenic sequestration. Splenectomy is performed in an attempt to reduce further events. Histologic studies of spleens have revealed the presence of granuloma-like nodules, known as Gamna-Gandy bodies with amorphous inclusions; however, their significance is unknown. The medical case records and histologic samples of consecutive children with sickle cell anemia treated with splenectomy between 2001 and 2007 at Our Lady's Children's Hospital, Dublin, were reviewed. Seventeen patients were identified. Gamna-Gandy bodies were studied by scanning electron microscopy and x ray fluorescence spectroscopy. Gamna-Gandy bodies were identified in 7 (41%) patients, and amorphous inclusions were always seen. Patient age correlated significantly with Gamna-Gandy bodies (P = .002). Scanning electron microscopic analysis demonstrated the crystalline nature of Gamna-Gandy bodies and the chemical composition (C 47.1%; O(2) 29.7%; P 9.0%; K(+) 0.4%; Ca(2+) 6.4%; Fe(2+) 7.4%), whereas x-ray diffraction studied the structure (CaPO(4) ? FeOH). A crystal-formation gradient was observed, increasing from the red pulp to the white pulp. Our study shows that Gamna-Gandy bodies contain crystals and that their formation is age dependent. We also demonstrated the crystal structure and chemical composition and the relationship between Gamna-Gandy bodies and chest crises presplenectomy or postsplenectomy. PMID- 22079356 TI - E-cadherin nuclear staining is useful for the diagnosis of ovarian adult granulosa cell tumor. AB - We recently have demonstrated nuclear localization of E-cadherin in ovarian adult granulosa cell tumors (Histopathology 2011;58:423). The purpose of the present study is to investigate the diagnostic utility of E-cadherin nuclear staining for the differential diagnosis between ovarian adult granulosa cell tumor and its morphological mimics. Tissue samples taken from 81 ovarian tumors and 20 extraovarian tumors were immunohistochemically stained using monoclonal anti-E cadherin antibody recognizing cytoplasmic domain (clone 36 supplied by BD Biosciences, San Jose, CA). The ovarian tumors consisted of 30 adult granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 5 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 18 endometrioid adenocarcinomas, and 10 poorly differentiated serous adenocarcinomas. Extraovarian tumors consisted of 16 uterine endometrial stromal neoplasms and 4 pulmonary small cell carcinomas. Only tumor cells with nuclear staining were considered positive in this study. Ninety percent of adult granulosa cell tumors, 67% of Sertoli-stromal cell tumors, 64% of fibrothecomas, 75% of endometrial stromal neoplasms, 75% of small cell carcinomas, and the one large cell neuroendocrine carcinoma showed E-cadherin nuclear expression, whereas all the ovarian carcinoid tumors, endometrioid adenocarcinomas, and poorly differentiated serous adenocarcinomas were negative. E-cadherin nuclear staining is useful in distinguishing between adult granulosa cell tumors and ovarian adenocarcinomas or carcinoid tumors. However, it is of limited use for distinguishing between adult granulosa cell tumors and endometrial stromal neoplasms or small cell carcinomas. E-cadherin should be included in the immunohistochemical panel for an accurate diagnosis of ovarian adult granulosa cell tumors. PMID- 22079357 TI - Nosology: infarction hematoma, a placental infarction encasing a hematoma. AB - Six cases of mothers whose placentas demonstrate multiple infarctions with a central intraparenchymal hematoma are presented. The histology is distinct from intervillous thrombus and Kline hemorrhage. The mothers have a history of multiple fetal losses, eclampsia/preeclampsia, and at least 1 case of documented recurrence. A distinct name is proposed for this lesion, infarction hematoma, which would help clarify further studies. PMID- 22079358 TI - The effect of luminance on simulated driving speed. AB - Perceived speed is modulated by a range of stimulus attributes such as contrast, luminance and adaptation duration. It has been suggested that such changes in perceived speed may influence driving behaviour. In order to evaluate the effect of luminance on driving speed we have measured subjects' driving speed in a driving simulator for a range of luminance and speed over time. The results indicate that reducing luminance results in a decrease in driving speed for all speeds measured. This reduction in driving speed at low luminance is consistent with previous findings that perceived speed increases at low luminance. However, the results also indicated that driving speed remained stable over a 30s period. The stability of driving speed over time is inconsistent with previous findings that perceived speed reduces exponentially as a function of adaptation duration. The results are suggestive of a scheme whereby driving speed is consistent with the known effects of luminance upon perceived speed but may also be modulated by higher order processes that serve to maintain a constant speed over time. PMID- 22079359 TI - Initial experience with repetitive transarterial chemoembolization (TACE) as a third line treatment of ovarian cancer metastasis to the liver: indications, outcomes and role in patient's management. AB - OBJECTIVE: To evaluate local tumor control and survival data after transarterial chemoembolization (TACE) with different drug combinations in the palliative third line treatment of patients with ovarian cancer liver metastases. METHODS: Sixty five patients (mean age: 51.5 year) with unresectable hematogenous hepatic metastases of ovarian cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. The local chemotherapy protocol consisted of Mitomycin (group 1) (n=14; 21.5%), Mitomycin with Gemcitabine (group 2) (n=26; 40%), or Mitomycin with Gemcitabine and Cisplatin (group 3) (n=25; 38.5%). Embolization was performed with Lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST criteria. Survival data were calculated according to the Kaplan-Meier method. RESULTS: The local tumor control was: partial response (PR) in 16.9% (n=11), stable disease (SD) in 58.5% (n=38) and progressive disease (PD) in 24.6% (n=16) of patients. In group 1, we observed SD in 78.6% (11/14), and PD in 21.4% (3/14) of patients. In group 2, PR in 7.7% (2/26), SD in 57.7% (15/26), and PD in 34.6% (9/26) of patients. In group 3, PR in 36% (9/25), SD in 48% (12/25), and PD in 16% (4/25) of patients. Survival rate from the start of TACE was 58% after 1-year, 19% after 2-years, and 13% after 3-years. The median and mean survival times were 14 and 18.5 months without statistically significant difference for the 3 groups of patients (p=0.502). CONCLUSION: Transarterial chemoembolization is effective palliative treatment in achieving local control in selected patients with liver metastases from ovarian cancer. PMID- 22079360 TI - Combined methotrexate-dactinomycin: an effective therapy for low-risk gestational trophoblastic neoplasia. AB - OBJECTIVE: The objective of this study is to examine the outcomes of combined chemotherapy using methotrexate and dactinomycin in the management of women with low-risk gestational trophoblastic neoplasia (GTN). The primary outcome is the total number of cycles of chemotherapy required to achieve a normal level of human chorionic gonadotropin (hCG). The secondary outcome is treatment-related toxicity. METHODS: A retrospective chart review of all patients with GTN treated between 1996-2007 and 1991-2007 was performed at the Alberta Cross Cancer Institute and the British Columbia Cancer Agency, respectively. Patients with low risk GTN, treated with 0.6 mg/m(2) dactinomycin (days 1 and 2) and methotrexate 100mg/m(2) were included. Toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. The number of cycles to achieve normalization of hCG was determined, and multivariate analyses were performed to identify factors associated with treatment duration. RESULTS: One hundred women were eligible. The average age was 29 years (range 15-46). The median number of cycles to achieve a normal hCG was 3 (range 1-11). Two patients required second-line treatment and one patient chose to proceed with hysterectomy. Ninety-eight percent of patients were primarily cured with this regimen, and 2 were cured with second line treatment. Grade 3 and 4 hematologic toxicities were experienced by 12% and 8% of patients, respectively. Grade 2 and 3 stomatitis or mucositis were noted in 44% and 3% of patients, respectively. CONCLUSIONS: Low-risk GTN is reliably and rapidly cured with combined methotrexate-dactinomycin. Toxicity is modest. PMID- 22079361 TI - A phase II trial of radiation therapy and weekly cisplatin chemotherapy for the treatment of locally-advanced squamous cell carcinoma of the vulva: a gynecologic oncology group study. AB - OBJECTIVES: To determine the efficacy and toxicity of radiation therapy and concurrent weekly cisplatin chemotherapy in achieving a complete clinical and pathologic response when used for the primary treatment of locally-advanced vulvar carcinoma. METHODS: Patients with locally-advanced (T3 or T4 tumors not amenable to surgical resection via radical vulvectomy), previously untreated squamous cell carcinoma of the vulva were treated with radiation (1.8 Gy daily * 32 fractions=57.6 Gy) plus weekly cisplatin (40 mg/m(2)) followed by surgical resection of residual tumor (or biopsy to confirm complete clinical response). Management of the groin lymph nodes was standardized and was not a statistical endpoint. Primary endpoints were complete clinical and pathologic response rates of the primary vulvar tumor. RESULTS: A planned interim analysis indicated sufficient activity to reopen the study to a second stage of accrual. Among 58 evaluable patients, there were 40 (69%) who completed study treatment. Reasons for prematurely discontinuing treatment included: patient refusal (N=4), toxicity (N=9), death (N=2), other (N=3). There were 37 patients with a complete clinical response (37/58; 64%). Among these women there were 34 who underwent surgical biopsy and 29 (78%) who also had a complete pathological response. Common adverse effects included leukopenia, pain, radiation dermatitis, pain, or metabolic changes. CONCLUSIONS: This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with acceptable toxicity. PMID- 22079362 TI - Experiences of care delivery: endometrial cancer survivors at end of treatment. AB - OBJECTIVES: To gain a better understanding of the experiences of endometrial cancer patients at the transition from acute cancer treatment to well follow up care. METHODS: Cross-sectional mixed methods (survey and focus groups) study to examine and describe endometrial cancer survivor's experience of the transition to survivorship including their knowledge of survivorship issues, feeling of preparedness, health related distress and perspectives on care delivery and end of treatment transitions. RESULTS: Survey data (n=169) and focus group data (n=14) suggests that a large majority of endometrial cancer survivors are not provided with any formal transition planning or documentation and as a result feel ill-prepared for the post treatment phase of survivorship. The majority of women in this study reported that they were not aware of their risk for recurrence or how to monitor for this and they were not provided with clear information in this regard. They were also unsure of the health risks and long term and late effects of cancer and how to find information about them and resources to manage them. A substantial minority (30-40%) of women continued to be frustrated and discouraged by their health problems. Few participants had been told about the resources and supports that are available to them and their families/friends or were not provided with any information about self-management tools or education that could be helpful for them in their recovery. CONCLUSIONS: Both the quantitative and qualitative results in our study suggest that quality of care for endometrial cancer survivors must begin to shift from a purely disease-focused approach to a wellness-centered approach that provides coordinated, patient-centered, comprehensive care and more formalized transition care planning. PMID- 22079363 TI - Comparison of platelet clumping and complete blood count results with Sysmex XT 2000iV in feline blood sampled on EDTA or EDTA plus CTAD (citrate, theophylline, adenosine and dipyridamole). AB - False thrombocytopenia may result from platelet aggregation, especially in feline ethylenediamine tetra-acetic acid (EDTA) blood specimens. Citrate, theophylline, adenosine and dipyridamole (CTAD) was added to 46 feline EDTA specimens to test its anti-aggregation action. Platelet aggregation was estimated from blood films and a complete blood count was performed with a Sysmex XT-2000iV analyser. Platelet aggregation score was >2 in 11/46 EDTA tubes and only in one EDTA+CTAD specimen. The platelet count was higher in all CTAD-supplemented tubes except one, medians measured by cytometry being 225.5 * 10(9)/l and 249.0 * 10(9)/l in EDTA and EDTA+CTAD, respectively (P = 0.007). Adding CTAD had statistically and analytically significant but moderate effects on other blood variables, the most intense variations being observed for reticulocytes (about 3% higher in EDTA specimens) and reticulocyte indexes. Addition of CTAD to EDTA when sampling feline blood is a useful option to reduce platelet clumping. PMID- 22079364 TI - Phosphorylated smooth muscle heavy meromyosin shows an open conformation linked to activation. AB - Smooth muscle myosin and smooth muscle heavy meromyosin (smHMM) are activated by regulatory light chain phosphorylation, but the mechanism remains unclear. Dephosphorylated, inactive smHMM assumes a closed conformation with asymmetric intramolecular head-head interactions between motor domains. The "free head" can bind to actin, but the actin binding interface of the "blocked head" is involved in interactions with the free head. We report here a three-dimensional structure for phosphorylated, active smHMM obtained using electron crystallography of two dimensional arrays. Head-head interactions of phosphorylated smHMM resemble those found in the dephosphorylated state but occur between different molecules, not within the same molecule. The light chain binding domain structure of phosphorylated smHMM differs markedly from that of the "blocked" head of dephosphorylated smHMM. We hypothesize that regulatory light chain phosphorylation opens the inhibited conformation primarily by its effect on the blocked head. Singly phosphorylated smHMM is not compatible with the closed conformation if the blocked head is phosphorylated. This concept has implications for the extent of myosin activation at low levels of phosphorylation in smooth muscle. PMID- 22079365 TI - The structure of Aquifex aeolicus ribosomal protein S8 reveals a unique subdomain that contributes to an extremely tight association with 16S rRNA. AB - The assembly of ribonucleoprotein complexes occurs under a broad range of conditions, but the principles that promote assembly and allow function at high temperature are poorly understood. The ribosomal protein S8 from Aquifex aeolicus (AS8) is unique in that there is a 41-residue insertion in the consensus S8 sequence. In addition, AS8 exhibits an unusually high affinity for the 16S ribosomal RNA, characterized by a picomolar dissociation constant that is approximately 26,000-fold tighter than the equivalent interaction from Escherichia coli. Deletion analysis demonstrated that binding to the minimal site on helix 21 occurred at the same nanomolar affinity found for other bacterial species. The additional affinity required the presence of a three-helix junction between helices 20, 21, and 22. The crystal structure of AS8 was solved, revealing the helix-loop-helix geometry of the unique AS8 insertion region, while the core of the molecule is conserved with known S8 structures. The AS8 structure was modeled onto the structure of the 30S ribosomal subunit from E. coli, suggesting the possibility that the unique subdomain provides additional backbone and side-chain contacts between the protein and an unpaired base within the three way junction of helices 20, 21, and 22. Point mutations in the protein insertion subdomain resulted in a significantly reduced RNA binding affinity with respect to wild-type AS8. These results indicate that the AS8-specific subdomain provides additional interactions with the three-way junction that contribute to the extremely tight binding to ribosomal RNA. PMID- 22079366 TI - YhiQ is RsmJ, the methyltransferase responsible for methylation of G1516 in 16S rRNA of E. coli. AB - Ten methyltransferases and one pseudouridine synthase are required for complete modification of the small ribosomal subunit in Escherichia coli. Nine methyltransferases, as well as the pseudouridine synthase, are already known. Here, we identify RsmJ, the last unknown methyltransferase required for methylation of m(2)G1516 in 16S ribosomal RNA (rRNA), as the protein encoded by yhiQ. Reverse transcription primer extension analysis reveals that rRNA extracted from a yhiQ deletion strain is not methylated at G1516. Moreover, methylation is restored upon gene complementation. Also, purified recombinant YhiQ specifically methylates 30S subunits extracted from the deletion strain. The absence of the yhiQ gene leads to a cold-sensitive phenotype. Based on these data, we propose that the yhiQ gene be renamed rsmJ. PMID- 22079368 TI - Treatment of osteoporosis in women intolerant of oral bisphosphonates. AB - In the past 15 years, oral bisphosphonate therapy has become the mainstay of pharmacological management in patients with osteoporosis. In the UK, alendronate is the drug of first choice, based on clinical efficacy data and cost. However, some patients are unable to take oral bisphosphonates for a number of reasons. In this article, we review the practical management of such cases, including strategies for monitoring adherence and switching to alternative oral agents (e.g. risedronate, strontium ranelate, raloxifene). In some cases, alternative parenteral agents may be considered, including intravenous bisphosphonates, parathyroid hormone therapies and denosumab. Specific concerns about safe prescribing are considered, when prescribing potent anti-resorptive medications, particularly relating to renal function and vitamin D deficiency. Finally, consideration is given to clinical risk factors, including aspects of lifestyle which may be modified to decrease fracture risk. PMID- 22079367 TI - Intra-chain 3D segment swapping spawns the evolution of new multidomain protein architectures. AB - Multidomain proteins form in evolution through the concatenation of domains, but structural domains may comprise multiple segments of the chain. In this work, we demonstrate that new multidomain architectures can evolve by an apparent three dimensional swap of segments between structurally similar domains within a single chain monomer. By a comprehensive structural search of the current Protein Data Bank (PDB), we identified 32 well-defined segment-swapped proteins (SSPs) belonging to 18 structural families. Nearly 13% of all multidomain proteins in the PDB may have a segment-swapped evolutionary precursor as estimated by more permissive searching criteria. The formation of SSPs can be explained by two principal evolutionary mechanisms: (i) domain swapping and fusion (DSF) and (ii) circular permutation (CP). By large-scale comparative analyses using structural alignment and hidden Markov model methods, it was found that the majority of SSPs have evolved via the DSF mechanism, and a much smaller fraction, via CP. Functional analyses further revealed that segment swapping, which results in two linkers connecting the domains, may impart directed flexibility to multidomain proteins and contributes to the development of new functions. Thus, inter-domain segment swapping represents a novel general mechanism by which new protein folds and multidomain architectures arise in evolution, and SSPs have structural and functional properties that make them worth defining as a separate group. PMID- 22079369 TI - TNFRSF11B gene haplotype and its association with bone mineral density variations in postmenopausal Mexican-Mestizo women. AB - OBJECTIVE: Osteoporosis is a complex health disease characterized by low bone mineral density (BMD), which is determined by an interaction of genetics with metabolic and environmental factors. The tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) gene, has been investigated in relation to BMD. Three polymorphisms in/nearby TNFRSF11B have been associated with BMD variations in some populations. The aim of this study was to investigate the possible association among three SNPs of TNFRSF11B and their haplotypes with the presence of BMD variations in postmenopausal Mexican Mestizo women. SUBJECTS AND METHODS: One thousand unrelated postmenopausal women of Mexican-Mestizo ethnic origin, who attended the outpatient clinic for routine, general medical evaluation, were invited and 750 women accepted to participate in the study. A structured questionnaire for risk factors was applied and BMD was measured in total hip and lumbar spine by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Three single-nucleotide polymorphisms in TNFRSF11B gene were studied: rs4355801, rs2073618, and rs6993813. Real-time PCR allelic discrimination was used for genotyping. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis was conducted. RESULTS: Of the subjects, 31% had osteoporosis, 45.1% had osteopenia, and 23.9% had normal BMD. Genotype and allele distributions showed no significant differences; however, A-G-T haplotype was associated with variations in femoral neck BMD (P=0.022). CONCLUSIONS: In our study population, analysis of the haplotypes of TNFRSF11B is a better genetic marker for variations in BMD. PMID- 22079370 TI - Degradation resistance of ormocer- and dimethacrylate-based matrices with different filler contents. AB - OBJECTIVES: To investigate the influence of matrix and filler content on degradation resistance of an experimental pure-ormocer and an dimethacrylate based composite derived from a commercially available material. MATERIALS AND METHODS: A dimethacrylate- Grandio (GR) and a model pure ormocer-based-matrix ORMOCER (ORM) were used. Each material had three different types according to their filler content (% w/w): regular (87% and 86%), flowable (80% and 79%) and fissure sealer (70% and 69%) for GR and ORM respectively. Disc-shaped (1 mm thickness*10 mm diameter) samples were prepared for each material (n=6). Water sorption and solubility tests were adapted from ISO4049. To evaluate porosity, specimens were scanned at a resolution of 19.4 MUm and 3D reconstructions were made. The volume ratio of pores in the specimens were calculated and expressed as percentages. The results were submitted to 2-way ANOVA (factors: matrix and filler content) and Tukey post-hoc statistic test (p=0.05). RESULTS: Filler content influenced the water sorption for the ormocer-matrix and the water solubility for the dimethacrylates. ORMOCER regular was a less porous material compared to flowable and sealer formulations. On the other hand, the filler content had no effect on porosity for Grandio. CONCLUSION: Modifications made in the pure ormocer-matrix formulation were not significantly important to produce a more water-stable material compared to the dimethacrylate-matrix composite materials. PMID- 22079371 TI - Clinical guidelines for treating caries in adults following a minimal intervention policy--evidence and consensus based report. AB - OBJECTIVES: In 2002, FDI (World Dental Federation) published a policy advocating that caries be treated by minimal intervention (MI). This MI policy has been accepted worldwide and is taught in universities. But acceptance in general dental practice has been slower, especially in Japan where healthcare payment and practice favour drilling and filling. To help disseminate this MI policy into general practice, the Japanese Society of Conservative Dentistry developed an evidence-based clinical guideline for restoring carious permanent teeth in adult patients. METHODS: The guideline was developed by a committee of nine university clinicians and a librarian. The committee selected the most frequent clinical questions in treating caries and used electronic databases to search and assess the best scientific evidence for each. Members then added their clinical experience and discussed to reach consensus on each question on treating caries with MI policy. Graded recommendations and guidance were made for each clinical question. The provisional guideline was strengthened after review and discussion with university researchers and general practitioners. RESULTS: The guideline addresses the 16 most frequent clinical questions in treating adult caries, including restorative methods and how to tackle root caries. Recommendations for treatment using MI policy were developed using the best scientific evidence and consensus of experienced clinicians. CLINICAL SIGNIFICANCE: The guideline offers a practical expert view of treating caries with the MI policy that incorporates the best scientific evidence, the latest techniques, the most preferable materials and the general consensus of expert clinicians. PMID- 22079372 TI - Outcome after homograft redo operation in aortic position. AB - OBJECTIVE: Since 1992, homografts have been implanted in our institution. After initial sub-coronary implantation of the homograft, our preferred technique for aortic-valve replacement with homografts became root replacement, which poses a surgical challenge whenever redo procedures are necessary. The aim of the present study was to evaluate the outcome after homograft redo surgery, based on prospective data from the biggest patient cohort in Germany for this procedure. METHODS: Between May 1992 and August 2009, 363 adult patients underwent aortic valve replacement with homografts in our cardiac surgery department. Homograft replacement was indicated in 90 of these 363 patients due to degenerative or infective conditions, and these were analysed. RESULTS: In these 73 male and 17 female patients (mean age at redo operation 62.0 years), homograft explantation was necessary due to infection (n = 14) or degeneration (stenosis n = 19, regurgitation > II degrees n = 57). Mean time between homograft implantation and redo operation was 8.4 +/- 3.6 years (range 0.0-15.5 years). Redo valve replacement through the aorta/homograft was done in 86 cases (valve into homograft wall = 80, total replacement of the homograft = 6) and trans-apical homograft replacement with an Edwards Sapien(r) Trans-catheter valve in four. Thirteen additional procedures were performed: bypass surgery (n = 1), mitral valve repair (n = 6), replacement of the ascending aorta (n = 5) and tricuspid valve repair (n = 1). Thirty-day mortality was 8.9% (n = 8, all of these patients presented with a homograft infection; five patients had a homograft reinfection). Survival rates after 1 and 5 years were 86.0% and 77.4%, respectively. CONCLUSIONS: The risk for a redo procedure after aortic-valve replacement with a homograft seems to be acceptable when compared with other prostheses. Mortality was, however, elevated in patients with a homograft infection. Trans-apical procedures are safe and feasible and might be our preferred technique for the future. Valve infections still remain a contraindication for trans- apical procedures. PMID- 22079373 TI - Expression of recombinant HAO3 from an Iranian isolate of Hyalomma anatolicum anatolicum in Pichia pastoris and evaluation of its antigenicity. AB - Hyalomma anatolicum anatolicum tick is considered as one of the main problem of ruminants' productivity in endemic countries such as parts of Africa, the Middle East and India. The disease is economically important and hence, its control and eradication is a priority. This problem reinforces the need for alternative approach like vaccine to control tick infestations instead of continuous application of acaricide which led to the natural selection of the acaricide resistant ticks. Therefore, the present study provided evidence for the construction of transformant containing the chromosomally integrated multi-copy expression cassettes of HAO3, its successful and efficient expression in Pichia pastoris yeast and purification of the secreted protein by ultrafiltration (UF) system in a high level yield and purity. The result of antigenicity assay for the rHAO3 protein pointed well toward its capability for the elicitation of antibody response in immunized rabbits. Interestingly, the results indicated that the expressed HAO3 protein reacted well with mid gut antigen (MGAg) and rBm86 (Gavac) antisera in ELISA and western blot assays making it evident that the epitopes present in expressed protein are well recognized by the antibodies against MGAg and rBm86 proteins. Moreover, the presence of cross-reactive epitopes between rHAO3 protein with its native antigen from mid gut cells was also determined. PMID- 22079374 TI - Improved detection of Trypanosoma brucei by lysis of red blood cells, concentration and LED fluorescence microscopy. AB - Confirmatory diagnosis of African trypanosomiasis relies on demonstration of parasites in body fluids by bright field microscopy. The parasitaemia in infected patients and animals is usually low, and concentration methods are used to try and increase the chances of seeing parasites. Recently, fluorescence microscopes using light-emitting diodes (LED) have been developed. Since they emit strong light, their use does not require a dark room, making field application a possibility. We have combined LED fluorescence microscopy with lysis of red blood cells (RBC) to improve the sensitivity and speed of detecting trypanosomes. In studies conducted at four centers in Uganda and the Democratic Republic of the Congo, parasitaemic blood was serially diluted and the RBCs lysed using commercial buffer. Samples were then concentrated by centrifugation, and different volumes of the sediment used to make thin and thick smears. Next, these were stained with acridine orange or Giemsa, and examined using an LED microscope under fluorescence or bright light, respectively. Detection of parasites was significantly improved by RBC lysis and concentration, regardless of the staining and microscopy method used. Further improvements were made when smears were prepared using larger volumes of sediment. The best results were obtained with thin smears prepared using 20 MUl of sediment and stained with acridine orange. The time taken to see the first parasite was dramatically reduced when smears were examined by LED fluorescence microscopy, compared to bright light. LED fluorescence microscopy was found to be easier and requiring less visual effort than bright field microscopy. These studies demonstrate the potential for incremental improvement in detection of Trypanosoma brucei by combining LED fluorescence microscopy with RBC lysis and concentration. The lysis and concentration method may also be useful in sample preparation for other diagnostic tests for trypanosomiasis. PMID- 22079375 TI - The subgenus Adlerius Nitzulescu (Diptera, Psychodidae, Phlebotomus) in Iran. AB - Phlebotomine sandflies of the subgenus Adlerius (Diptera: Psychodidae) includes 20 described species and two unnamed from Afghanistan. The female sandflies of this subgenus are considered as indistinguishable morphologically and their identification is based on the identification of associated males. Some species of Adlerius are suspected vectors of visceral leishmaniasis and at least one species has been implicated as a vector of cutaneous leishmaniasis. Four species of Adlerius have been recorded in Iran in the past: P. brevis Theodor and Mesghali, 1964, P. halepensis Theodor, 1948, P. longiductus Parrot, 1928 and P. balcanicus Theodor, 1948. The present study based on a field work carried out all over Iran reports two new species in the country: Phlebotomus turanicus Artemiev 1974 and Phlebotomus salangensis Artemiev, 1978. They have been caught from the North-East of Iran in provinces bordering Turkmenistan and Afghanistan, respectively. A review of the distribution of the Adlerius species of Iran is proposed. PMID- 22079376 TI - Mammalian cell invasion by closely related Trypanosoma species T. dionisii and T. cruzi. AB - Protozoan parasites of the genus Trypanosoma can infect virtually all mammalian species. Within this genus, Trypanosoma dionisii from bats and Trypanosoma cruzi that causes Chagas' disease, belonging to the subgenus Schizotrypanum, can invade mammalian cells. The mechanisms of cell invasion by T. dionisii are poorly understood. To address that question, metacyclic trypomastigotes (MT) and human epithelial HeLa cells were used. Similarly to genetically divergent T. cruzi strains G (TcI) and CL (TcVI), associated, respectively with marsupial and human infections, T. dionisii infectivity increased under nutritional stress, a condition that induces host cell lysosome exocytosis required for parasite internalization. For efficient internalization, T. dionisii depended on MT protein tyrosine kinase (PTK) and Ca(2+) mobilization from acidocalcisomes, whereas T. cruzi strains also relied on phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC) and Ca(2+) released from thapsigargin-sensitive compartments. T. dionisii-induced signaling in host cells implicated PKC and Ca(2+) mobilized from thapsigargin-sensitive stores, like T. cruzi, but without PI3K involvement. Unlike T. cruzi, T. dionisii metacyclic forms did not use l proline as source of energy required for internalization. Molecules related to T. cruzi surface glycoproteins involved in MT-host cell interaction were undetectable in T. dionisii. The difference in the surface profile of the two species was also inferred from the susceptibility of T. dionisii metacyclic forms to complement-mediated lysis, as opposed to complete resistance of T. cruzi. In summary, the two Trypanosoma species display distinct surface profiles but invade host cells through a common mechanism involving lysosome mobilization to the site of parasite entry. PMID- 22079377 TI - Chicken oviduct-specific expression of transgene by a hybrid ovalbumin enhancer and the Tet expression system. AB - We generated genetically manipulated chickens and quail by infecting them with a retroviral vector expressing the human growth hormone under the control of chicken ovalbumin promoter/enhancer up to -3861 bp from the transcriptional start site. The growth hormone was expressed in an oviduct-specific manner and was found in egg white, although its level was low. The DNA sequence of the integrated form of the viral vector in the packaging cells was shown to be truncated and contained only the sequence spanning -3861 to -1569 bp. This represented only the DNase I hypersensitive site (DHS) III of the 4 DHSs and lacked the proximal promoter of the ovalbumin control region. We found several TATA-like and other promoter motifs of approximately -1800 bp and considered that these promoter motifs and DHS III may cause weak but oviduct-specific expression of the growth hormone. To prove this hypothesis and apply this system to oviduct specific expression of the transgene, the truncated regulatory sequence was fused to an artificial transactivator-promoter system. In this system, initial weak but oviduct-specific expression of the Tet activator from the promoter element in the ovalbumin control sequence triggered a self-amplifying cycle of expression. DsRed was specifically expressed in oviduct cells of genetically manipulated chickens using this system. Furthermore, deletion of a short region possibly containing the promoter elements (-2112 to -1569 bp) completely abrogated oviduct-specific expression. Taken together, these results suggest that weak expression of this putative promoter causes oviduct-specific expression of the transgene. PMID- 22079378 TI - Synthesis and in vitro antiproliferative evaluation of pyrimido[5,4-c]quinoline-4 (3H)-one derivatives. AB - A series of pyrimido[5,4-c]quinoline-4-(3H)-one derivatives variously substituted at positions 2 and 3 were synthesized and evaluated for their in vitro antiproliferative activities against a panel of six human cancer cell lines. Biological evaluation revealed that the vast majority of derivatives exhibited moderate tumor growth inhibitory activities. In particular, compound 7e showed effective anti-tumor activity with broad-spectrum toward numerous cell lines and the most active member in this study. This derivative displaying significant activity against KB (IC(50): 4.9 MUM), CNE2 (IC(50): 13.8 MUM), MGC-803 (IC(50): 4.8 MUM), GLC-82 (IC(50): 7.88 MUM), MDA-MB-453 (IC(50): 18.2 MUM) and MCF-7 (IC(50): 10.1 MUM) cell lines could be considered as the most promising and useful template for future development to obtain more potent anti-tumor agent(s). PMID- 22079379 TI - Synthesis and antibacterial activity of naphthyridone derivatives containing mono/difluoro-methyloxime pyrrolidine scaffolds. AB - A series of novel naphthyridone derivatives containing mono/difluoro-methyloxime pyrrolidine scaffolds were designed and synthesized. These derivatives were initially evaluated for their in vitro antibacterial activity and compounds 13a1, b1 were chosen for further evaluation their in vivo activity against systemic infections in mice. The results indicate that all of the target compounds have considerable in vitro antibacterial activity. In the in vivo experiments, 13b1 was found to be more effective than the parent drug gemifloxacin against the tested five strains, and especially its activity (ED(50):21.27 mg/kg) is 5.2-6.1 times more potent than gemifloxacin and ciprofloxacin against clinically important Gram-negative pathogen Pseudomonas aeruginosa. PMID- 22079380 TI - Scandium oxide coated polycrystalline tungsten studied using emission microscopy and photoelectron spectroscopy. AB - Thermionic electron emission from 200 to 500 nm thick coatings of scandium oxide on tungsten foil have been examined in thermionic emission microscopy, spectroscopic photoelectron microcopy, synchrotron radiation and ultraviolet photoelectron spectroscopy (UPS). A clear dependence of the scandium oxide-W electron yield on the grain orientation of the polycrystalline tungsten is observed in thermionic emission and photoelectron emission. PMID- 22079381 TI - Gertrude Rempfer and the development of high resolution focused ion beam technology. AB - High resolution focused ion beam (FIB) technology depends on electrostatic optics. As a longtime researcher on electrostatic optics Dr. Gertrude Rempfer has had a great impact not only on the development of FIB technology but, as a result, also on several technology areas dependent on it. This paper provides a brief description of how that came about. PMID- 22079382 TI - Changes in ribosome biogenesis may induce cancer by down-regulating the cell tumor suppressor potential. AB - Many human pathological conditions, not linked to genetic alterations of oncogenes or tumor suppressors, are nevertheless associated with an increased risk of developing cancer, and some of them are characterized by quantitative and/or qualitative changes in ribosome biogenesis. Indeed, there is evidence that both an up-regulation of ribosome biogenesis, such as that occurring during the abnormal stimulation of cell growth, and intrinsic dysfunctions of ribosomes, such as those characterizing a series of inherited disorders, show an increased incidence of tumor onset. Here we discuss some recent insights into the mechanisms by which these alterations in ribosome biogenesis may facilitate tumorigenesis. PMID- 22079383 TI - Navigating the fine line between benefit and risk in chronic atrial fibrillation: rationale and design of the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY). AB - BACKGROUND: Health outcomes associated with atrial fibrillation (AF) continue to be poor and standard management often does not provide clinical stability. The Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY) compares the efficacy of a post-discharge, nurse-led, multi-disciplinary programme to optimise AF management with usual care. METHODS: SAFETY is a prospective, multi centre, randomised controlled trial with blinded-endpoint adjudication. A target of 320 hospitalised patients with a chronic form of AF will be randomised (stratified by "rate" versus "rhythm" control) to usual post-discharge care or the SAFETY Intervention (SI). The SI involves home-based assessment, extensive clinical profiling and the application of optimal gold-standard pharmacology which is individually tailored according to a "traffic light" framework based on clinical stability, risk profile and therapeutic management. The primary endpoint is event-free survival from all-cause death or unplanned readmission during 18-36 months follow-up. Secondary endpoints include rate of recurrent hospital stay, treatment success (i.e. maintenance of rhythm or rate control and/or application of anti-thrombotic therapy without a bleeding event) and cost-efficacy. RESULTS: With study recruitment to be completed in early 2012, the results of this study will be available in early 2014. CONCLUSIONS: If positive, SAFETY will represent a potentially cost-effective and readily applicable strategy to improve health outcomes in high risk individuals discharged from hospital with chronic AF. PMID- 22079384 TI - Flow patterns and wall shear stress distribution in human internal carotid arteries: the geometric effect on the risk for stenoses. AB - It has been widely observed that atherosclerotic stenosis occurs at sites with complex hemodynamics, such as arteries with high curvature or bifurcations. These regions usually have very low or highly oscillatory wall shear stress (WSS). In the present study, 3D sinusoidally pulsatile blood flow through the models of internal carotid artery (ICA) with different geometries was investigated with computational simulation. Three preferred sites of stenoses were found along the carotid siphon with low and highly oscillatory WSS. The risk for stenoses at these sites was scaled with the values of time-averaged WSS and oscillating shear index (OSI). The local risk for stenoses at every preferred site of stenoses was found different between 3 types of ICA, indicating that the geometry of the blood vessel plays significant roles in the atherogenesis. Specifically, the large curvature and planarity of the vessel were found to increase the risk for stenoses, because they tend to lower WSS and elevate OSI. Therefore, the geometric study makes it possible to estimate the stenosis location in the ICA siphon as long as the shape of ICA was measured. PMID- 22079385 TI - The shear mechanical properties of diabetic and non-diabetic plantar soft tissue. AB - Changes in the plantar soft tissue shear properties may contribute to ulceration in diabetic patients, however, little is known about these shear parameters. This study examines the elastic and viscoelastic shear behavior of both diabetic and non-diabetic plantar tissue. Previously compression tested plantar tissue specimens (n=54) at six relevant plantar locations (hallux, first, third, and fifth metatarsal heads, lateral midfoot, and calcaneus) from four cadaveric diabetic feet and five non-diabetic feet were utilized. Per in vivo data (i.e., combined deformation patterns of compression followed by shear), an initial static compressive strain (36-38%) was applied to the tissue followed by target shear strains of 50% and 85% of initial thickness. Triangle waves were used to quantify elastic parameters at both strain levels and a stress relaxation test (0.25 s ramp and 300 s hold) was used to quantify the viscoelastic parameters at the upper strain level. Several differences were found between test groups including a 52-62% increase in peak shear stress, a 63% increase in toe shear modulus, a 47% increase in final shear modulus, and a 67% increase in middle slope magnitude (sharper drop in relaxation) in the diabetic tissue. Beyond a 54% greater peak compressive stress in the third metatarsal compared to the lateral midfoot, there were no differences in shear properties between plantar locations. Notably, this study demonstrates that plantar soft tissue with diabetes is stiffer than healthy tissue, thereby compromising its ability to dissipate shear stresses borne by the foot that may increase ulceration risk. PMID- 22079386 TI - The knee adduction moment measured with an instrumented force shoe in patients with knee osteoarthritis. AB - The external knee adduction moment (KAdM) during gait is an important parameter in patients with knee osteoarthritis (OA). KAdM measurement is currently restricted to instruments only available in gait laboratories. However, ambulatory movement analysis technology, including instrumented force shoes (IFS) and inertial and magnetic measurement systems (IMMS), can measure kinetics and kinematics of human gait free of laboratory restrictions. The objective of this study was a quantitative validation of the accuracy of the KAdM in patients with knee OA, when estimated with an ambulatory-based method (AmbBM) versus a laboratory-based method (LabBM). AmbBM is employing the IFS and a linked-segment model, while LabBM is based on a force plate and optoelectronic marker system. Effects of ground reaction force (GRF), centre of pressure (CoP), and knee joint position measurement are evaluated separately. Twenty patients with knee OA were measured. The GRFs showed differences up to 0.22 N/kg, the CoPs showed differences up to 4 mm, and the medio-lateral and vertical knee position showed differences to 9 mm, between AmbBM and LabBM. The GRF caused an under-estimation in KAdM in early stance. However, this effect was counteracted by differences in CoP and joint position, resulting in a net 5% over-estimation. In midstance and late stance the accuracy of the KAdM was mainly limited by use of the linked segment model for joint position estimation, resulting in an under-estimation (midstance 6% and late stance 22%). Further improvements are needed in the estimation of joint position from segment orientation. PMID- 22079387 TI - Accuracy of finite element predictions in sideways load configurations for the proximal human femur. AB - Subject-specific finite element models have been used to predict stress-state and fracture risk in individual patients. While many studies analysed quasi-axial loading configurations, only few works simulated sideways load configurations, such as those arising in a fall. The majority among these latter directly predicted bone strength, without assessing elastic strain prediction accuracy. The aim of the present work was to evaluate if a subject-specific finite element modelling technique from CT data that accurately predicted strains in quasi-axial loading configurations is suitable to accurately predict strains also when applying low magnitude loads in sideways configurations. To this aim, a combined numerical-experimental study was performed to compare finite element predicted strains with strain-gauge measurements from three cadaver proximal femurs instrumented with sixteen strain rosettes and tested non-destructively under twelve loading configurations, spanning a wide cone (0-30 degrees for both adduction and internal rotation angles) of sideways fall scenarios. The results of the present study evidenced a satisfactory agreement between experimentally measured and predicted strains (R(2) greater than 0.9, RMSE% lower than 10%) and displacements. The achieved strain prediction accuracy is comparable to those obtained in state of the art studies in quasi-axial loading configurations. Still, the presence of the highest strain prediction errors (around 30%) in the lateral neck aspect would deserve attention in future studies targeting bone failure. PMID- 22079388 TI - Thalassaemia in pregnancy. AB - Thalassaemia is the most common monogenetic disease worldwide. Antenatal screening is effective and simple, and accurate genetic prenatal diagnosis can be achieved in early gestation. Less invasive methods are feasible with ultrasound fetal assessment for alpha-thalassaemia, analysis of circulating fetal nucleic acid in maternal plasma, and pre-implantation genetic diagnosis. Women with thalassaemia major and intermedia are at risk of various maternal complications, such as cardiac failure, alloimmunisation, viral infection, thrombosis, endocrine and bone disturbances. Therefore, it is prudent to adhere to a standard management plan in this group of pregnant women. Close monitoring of the maternal and fetal condition during pregnancy is essential, and various treatments, such as blood transfusion or postpartum prophylaxis for thromboembolism, may be indicated. After birth, resumption of iron chelation and bisphosphonates treatment is needed, and counselling on breast feeding and contraception should be given. PMID- 22079389 TI - Thrombophilia and early pregnancy loss. AB - Early pregnancy loss is the most common pregnancy complication. About 15% of pregnancies result in pregnancy loss and 1% of women experience recurrent miscarriage (more than three consecutive miscarriages). The influence of thrombophilia in pregnancy is a popular research topic in recurrent miscarriage. Both acquired and inherited thrombophilia are associated with a risk of pregnancy failure. Antiphospholipid syndrome is the only thrombophilia known to have a direct adverse effect on pregnancy. Historically, clinical research studying thrombophilia treatment in recurrent miscarriage has been of limited value owing to small participant numbers, poor study design and heterogeneity. The debate on the efficacy of aspirin and heparin has advanced with recently published randomised-controlled trials. Multi-centre collaboration is required to ascertain the effect of thrombophilia on early pregnancy loss and to establish an evidence based treatment protocol. PMID- 22079390 TI - Coenzyme Q(10), vitamin E, selenium, and methionine in the treatment of chronic recurrent viral mucocutaneous infections. AB - OBJECTIVE: Host defense and latency determinants in viral recurrent dermatologic infections are not entirely understood, as conventional protocols are inadequate to achieve fast healing and relapse prevention. Endogenously produced oxygen/nitrogen reactive species (ROS/RNS) are essential for antiviral immune defense, while their excess may aggravate skin inflammation. Here, we sought a nutritional approach capable of controlling ROS/RNS balance to accelerate recovery and inhibit recurrences of two mucocutaneous chronic DNA-virus infections. METHODS: Two controlled clinical trials evaluated the feasibility of ROS/RNS-modulating nutriceutical dosages of coenzyme Q(10), RRR-alpha-tocopherol, selenium aspartate, and L-methionine associated with established therapies. Clinical trial 1 evaluated 68 patients with relapsing human papillomavirus skin warts treated with cryotherapy followed by 180 d of nutriceutical/placebo administration. Clinical trial 2 compared the combination of acyclovir followed by 90 d of nutriceutical administration versus acyclovir alone in patients with recurrences of herpes simplex genitalis (n = 60) or herpes zoster (n = 29). Viral DNA levels were assessed by polymer chain reaction, biomarkers of antiviral defense (peroxynitrite and IFNalpha/gamma) and antioxidant capacity (lipophilic antioxidants and glutathione) were assayed by biochemical/enzyme-linked immunosorbent assay techniques in blood fractions. RESULTS: In both trials, the nutriceutical induced significantly faster healing (P < 0.01-0.05) with reduced incidence of relapses (P < 0.05) as compared to control groups, which was confirmed by decreased viral load and increased antiviral cytokine and peroxynitrite plasma levels. Plasma antioxidant capacity was higher (P < 0.01) in the experimental versus control groups. CONCLUSIONS: Results document positive clinical outcomes of the selected nutriceutical associated with conventional protocols in the management of relapsing mucocutaneous human papillomavirus and herpes infections. PMID- 22079391 TI - Coenzyme Q10 supplementation and exercise-induced oxidative stress in humans. AB - OBJECTIVE: The theoretically beneficial effects of coenzyme Q10 (Q10) on exercise related oxidative stress and physical capacity have not been confirmed to our knowledge by interventional supplementation studies. Our aim was to investigate further whether Q10 supplementation at a dose recommended by manufacturers influences these factors. METHODS: Using a randomized, double-blind, controlled design, we investigated the effect on physical capacity of 8 wk of treatment with a daily dose of 90 mg of Q10 (n = 12) compared with placebo (n = 11) in moderately trained healthy men 19 to 44 y old. Two days of individualized performance tests to physical exhaustion were performed before and after the intervention. Primary outcomes were maximal oxygen uptake, workload, and heart rate at the lactate threshold. Secondary outcomes were creatine kinase, hypoxanthine, and uric acid. RESULTS: No significant differences between the groups were discerned after the intervention for maximal oxygen uptake (-0.11 L/min, 95% confidence interval -0.31 to 0.08, P = 0.44), workload at lactate threshold (6.3 W, -13.4 to 25.9, P = 0.36), or heart rate at lactate threshold (2.0 beats/min, -4.9 to 8.9, P = 0.41). No differences between the groups were detected for hypoxanthine or uric acid (serum markers of oxidative stress) or creatine kinase (a marker of skeletal muscle damage). CONCLUSION: Although in theory Q10 could be beneficial for exercise capacity and in decreasing oxidative stress, the present study could not demonstrate that such effects exist after supplementation with a recommended dose. PMID- 22079392 TI - Effects of high-fat diet on plasma lipids, adiposity, and inflammatory markers in ovariectomized C57BL/6 mice. AB - OBJECTIVE: We hypothesized that a high-fat (HF) diet aggravates ovariectomy related complications. To test this hypothesis, ovariectomized (OVX) mice were fed a HF diet, and we investigated the lipid metabolism, adipose tissue remodeling, adipokines, and inflammatory cytokines. METHODS: To investigate the situation in a mouse model of ovariectomy, OVX and SHAM C57BL/6 mice fed a HF diet (60% fat) or standard chow (SC, 10% fat) were monitored for 18 wk. We evaluated daily food intake and weekly body weight. Mice were killed at 30 wk of age. Blood samples and adipose tissue were collected for biochemical, histologic, and molecular analysis. RESULTS: OVX groups showed atrophied uterus compared to the SHAM groups, ensuring the success of surgically induced menopause. Despite lower food intake, OVX-HF mice gained about 52% more weight and had heavier total body fats, especially in relation to ovarian fat pad (372%)-a visceral fat which is associated with increased pathogenicity in obesity, and showed larger adipocytes (30%) when compared to OVX-SC mice. Biochemical analysis showed that the OVX-HF mice had increased levels of serum total cholesterol (51%), greater serum triglycerides (158%), lower serum adiponectin (40%), and higher plasma leptin (323%) than OVX-SC mice. The obese group (OVX-HF) also had higher IL-6 levels than both SHAM-HF (241%) and OVX-SC mice (870%). CONCLUSION: OVX C57BL/6 mice fed HF diet had greater adipose fat pad, larger adipocytes, and increased inflammatory markers, reinforcing the idea that a HF diet aggravates the complications of ovariectomy-associated inflammation. PMID- 22079393 TI - Hypermethylation of repetitive DNA elements in livers of mice fed an atherogenic diet. AB - OBJECTIVE: DNA methylation status was examined in C57BL/6J obese mice fed an atherogenic diet (AD) to establish the correlation between epigenetic alterations and obesity-related abnormalities. METHODS: Six-week-old male C57BL/6J mice were fed a normal diet (ND) or AD for 8 wk. Methylation levels of global DNA and repetitive DNA elements in livers of ND-fed mice and AD-fed mice were examined. RESULTS: The total amounts of 5-MeC genomic contents in livers of AD-fed mice were increased as compared with those of ND-fed mice. Hypermethylation of repetitive DNA elements was observed in livers of AD-fed mice. CONCLUSION: Hypermethylation of repetitive DNA elements in livers of AD-fed mice proposes epigenetic changes by nutritional intervention. PMID- 22079394 TI - Effects of leucine supplementation and resistance exercise on dexamethasone induced muscle atrophy and insulin resistance in rats. AB - OBJECTIVE: We aimed to evaluate the effects of resistance exercise (RE) and leucine (LEU) supplementation on dexamethasone (DEXA)-induced muscle atrophy and insulin resistance. METHODS: Male Wistar rats were randomly divided into DEXA (DEX), DEXA + RE (DEX-RE), DEXA + LEU (DEX-LEU), and DEXA + RE + LEU (DEX-RE-LEU) groups. Each group received DEXA 5 mg . kg(-1) . d(-1) for 7 d from drinking water and were pair-fed to the DEX group; LEU-supplemented groups received 0.135 g . kg(-1) . d(-1) through gavage for 7 d; the RE protocol was based on three sessions of squat-type exercise composed by three sets of 10 repetitions at 70% of maximal voluntary strength capacity. RESULTS: The plantaris mass was significantly greater in both trained groups compared with the non-trained groups. Muscle cross-sectional area and fiber areas did not differ between groups. Both trained groups displayed significant increases in the number of intermediated fibers (IIa/IIx), a decreased number of fast-twitch fibers (IIb), an increased ratio of the proteins phospho(Ser2448)/total mammalian target of rapamycin and phospho(Thr389)/total 70-kDa ribosomal protein S6 kinase, and a decreased ratio of phospho(Ser253)/total Forkhead box protein-3a. Plasma glucose was significantly increased in the DEX-LEU group compared with the DEX group and RE significantly decreased hyperglycemia. The DEX-LEU group displayed decreased glucose transporter-4 translocation compared with the DEX group and RE restored this response. LEU supplementation worsened insulin sensitivity and did not attenuate muscle wasting in rats treated with DEXA. Conversely, RE modulated glucose homeostasis and fiber type transition in the plantaris muscle. CONCLUSION: Resistance exercise but not LEU supplementation promoted fiber type transition and improved glucose homeostasis in DEXA-treated rats. PMID- 22079396 TI - Accuracy of GFR predictive equations in renal transplantation: validation of a new turbidimetric cystatin C assay on Architect c8000. AB - OBJECTIVES: To evaluate the Sentinel-PETIA cystatin C on Architect c8000 analyzer. DESIGN AND METHODS: We assessed analytical performances and clinical relevance by comparison with a reference isotopic method in kidney transplant recipients. RESULTS: This assay exhibited reliable precision and was close to the non standardized Siemens-PENIA method. All tested equations allowed reliable assessment of GFR. CONCLUSIONS: Cystatin C improved GFR determination at the critical level of 60 mL/min/1.73 m2. New formulas might be necessary after IFCC standardization. PMID- 22079395 TI - Impact of barbecued meat consumed in pregnancy on birth outcomes accounting for personal prenatal exposure to airborne polycyclic aromatic hydrocarbons: Birth cohort study in Poland. AB - OBJECTIVE: We previously reported an association between prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) and lower birth weight, birth length, and head circumference. The main goal of the present analysis was to assess the possible impact of coexposure to PAH-containing barbecued meat consumed during pregnancy on birth outcomes. MATERIALS AND METHODS: The birth cohort consisted of 432 pregnant women who gave birth at term (>36 wk of gestation). Only non-smoking women with singleton pregnancies, 18-35 y of age, and who were free from chronic diseases such as diabetes and hypertension, were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birth weight, length, and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child's sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy), and prenatal environmental tobacco smoke. RESULTS: The multivariable regression model showed a significant deficit in birth weight associated with barbecued meat consumption in pregnancy (coeff = -106.0 g; 95%CI: -293.3, -35.8). The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = -164.6 g; 95%CI: -172.3, -34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: 419.0, -9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birth weight could not have been mediated by a shortened gestation period. CONCLUSION: In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development. PMID- 22079397 TI - Reduction of butyrylcholinesterase activity in plasma from patients with disorders of propionate metabolism is prevented by treatment with L-carnitine and protein restriction. AB - OBJECTIVE: We investigated the relationship between butyrylcholinesterase (BuChE) activity and lipid oxidative damage in patients with disorders of propionate metabolism, before and after treatment with protein restriction and L-carnitine. DESIGN AND METHODS: BuChE activity and malondialdehyde (MDA) were measured in plasma from eight untreated patients (at diagnosis) and from seven patients under treatment with protein restriction and L-carnitne supplementation (100mg/kg/day). RESULTS: We verified a significant reduction of butyrylcholinesterase activity, as well as an increased MDA formation in plasma from untreated patients. However, treated patients presented MDA and BuChE activity similar to controls. Furthermore, butyrylcholinesterase activity was negatively correlated with MDA concentrations in these patients. CONCLUSION: The results suggest that an increased free radicals formation may be involved in the decrease of butyrylcholinesterase activity, possibly contributing to the neurological damage of these disorders, and that treatment with L-carnitine and low-protein diet possibly is able to prevent this damage. PMID- 22079398 TI - Social memories in rodents: methods, mechanisms and modulation by stress. AB - Intact social memory forms the basis of meaningful interactions between individuals. Many factors can modulate the quality of social memory, and these have been studied in detail in rodents. Social memory, however, cannot be considered a single entity. The term social memory reflects different processes, such as social recognition of a novel conspecific individual and social learning (or 'learning from others'). This review summarizes the findings obtained with behavioral paradigms that were developed for the study of memory formation by social recognition and social learning. In particular, we focus on studies that include tests for social habituation/discrimination paradigms, tests for memory of a previously established social hierarchy and the social transmission of the food preference test. The role of individual differences and the main neurobiological mechanisms (i.e., the brain regions and neurochemical systems involved) that have been implicated in each of these types of social-related memories are reviewed. In addition, we address the key modulatory influence of stress on the formation of these types of memories; discussing the contribution of central (corticotropin-releasing factor, CRF) and peripheral (glucocorticoids) stress systems and their interactions with the social neuropeptide systems. Overall, we present here a general overview of the current state of a thriving research area within the field of social neuroscience. PMID- 22079399 TI - Structural and physiological phenotypes of disease-linked lamin mutations in C. elegans. AB - The nuclear lamina is a major structural element of the nucleus and is predominately composed of the intermediate filament lamin proteins. Missense mutations in the human lamins A/C cause a family of laminopathic diseases, with no known mechanistic link between the position of the mutation and the resulting disease phenotypes. The Caenorhabditis elegans lamin (Ce-lamin) is structurally and functionally homologous to human lamins, and recent advances have allowed detailed structural analysis of Ce-lamin filaments both in vitro and in vivo. Here, we studied the effect of laminopathic mutations on Ce-lamin filament assembly in vitro and the corresponding physiological phenotypes in animals. We focused on three disease-linked mutations, Q159K, T164P, and L535P, which have previously been shown to affect lamin structure and nuclear localization. Mutations prevented the proper assembly of Ce-lamin into filament and/or paracrystalline arrays. Disease-like phenotypes were observed in strains expressing low levels of these mutant lamins, including decreased fertility and motility coincident with muscle lesions. In addition, the Q159K- and T164P expressing strains showed a reduced lifespan. Thus, different disease-linked mutations in Ce-lamin exhibit major effects in vivo and in vitro. Using C. elegans as a model system, a comprehensive analysis of the effects of specific lamin mutations from the level of in vitro filament assembly to the physiology of the organism will help uncover the mechanistic differences between these different lamin mutations. PMID- 22079400 TI - Finding rigid bodies in protein structures: Application to flexible fitting into cryoEM maps. AB - We present RIBFIND, a method for detecting flexibility in protein structures via the clustering of secondary structural elements (SSEs) into rigid bodies. To test the usefulness of the method in refining atomic structures within cryoEM density we incorporated it into our flexible fitting protocol (Flex-EM). Our benchmark includes 13 pairs of protein structures in two conformations each, one of which is represented by a corresponding cryoEM map. Refining the structures in simulated and experimental maps at the 5-15A resolution range using rigid bodies identified by RIBFIND shows a significant improvement over using individual SSEs as rigid bodies. For the 15A resolution simulated maps, using RIBFIND-based rigid bodies improves the initial fits by 40.64% on average, as compared to 26.52% when using individual SSEs. Furthermore, for some test cases we show that at the sub nanometer resolution range the fits can be further improved by applying a two stage refinement protocol (using RIBFIND-based refinement followed by an SSE based refinement). The method is stand-alone and could serve as a general interactive tool for guiding flexible fitting into EM maps. PMID- 22079401 TI - Microstructure-stiffness relationships of ten European and tropical hardwood species. AB - Hardwood species exhibit a huge anatomical variability. This makes them perfect study objects for exploring relations between structural features at different length scales and corresponding stiffness properties of wood. We carry out microscopic analysis, nanoindentation tests, as well as macroscale ultrasonic and quasi-static tension tests and build a complete set of microstructural and corresponding micromechanical data of ten different (European and tropical) hardwood species. In addition, we apply micromechanical modeling to further elucidate the individual influences of particular structural features, which might appear only in a superimposed manner in experiments. The test results confirm the dominant influences of the microfibril angle on the stiffness at cell wall level and of density at the macroscopic scale. Vessels and ray cells affect the macroscopic stiffness of the wood tissue not only through their content, but also through their arrangement and shape: A ring-porous structure results in comparably higher longitudinal but lower radial stiffness than a diffuse-porous one. As for ray cells, large and particularly compactly shaped bundles might reduce the stiffness in tangential direction because of the fiber deviations they cause. Moreover, vessel and ray content might affect the relation between nanoindentation modulus and density-corrected macroscopic longitudinal stiffness. PMID- 22079402 TI - Adaptive volumetric modulated arc treatment planning for esophageal cancers using cone beam computed tomography. AB - PURPOSE: To assess the potential of cone beam CT (CBCT) derived adaptive RapidArc treatment for esophageal cancers in reducing the dose to organs at risk (OAR). METHODS AND MATERIALS: Ten patients with esophageal cancer were CT scanned in free breathing pattern. The PTV is generated by adding a 3D margin of 1 cm to the CTV as per ICRU 62 recommendations. The double arc RapidArc plan (Clin_RA) was generated for the PTV. Patients were setup using kV orthogonal images and kV-CBCT scan was acquired daily during first week of therapy, then weekly. These images were exported to the Eclipse TPS. The adaptive CTV which includes tumor and involved nodes was delineated in each CBCT image set for the length of the PTV. The composite CTV from first week CBCT was generated using Boolean union operator and 5 mm margin was added circumferentially to generate adaptive PTV (PTV1). Adaptive RapidArc plan (Adap_RA) was generated. NTCP and DVH of the OARs of the two plans were compared. Similarly, PTV2 was generated from weekly CBCT. PTV2 was evaluated for the coverage of 95% isodose of Adap_RA plan. RESULTS: The PTV1 and PTV2 volumes covered by 95% isodose in adaptive plans were 93.51 +/- 1.17% and 94.59 +/- 1.43% respectively. The lung V(10Gy,)V(20Gy) and mean dose in Adap_RA plan was reduced by 17.43% (p = 0.0012), 34.64% (p = 0.0019) and 16.50% (p = 0.0002) respectively compared to Clin_RA. The Adap_RA plan reduces the heart D(35%) and mean dose by 17.35% (p = 0.0011) and 17.16% (p = 0.0012). No significant reduction in spinal cord and liver doses were observed. NTCP for the lung (0.42% vs. 0.08%) and heart (1.39% vs. 0.090%) was reduced significantly in adaptive plans. CONCLUSION: The adaptive re-planning strategy based on the first week CBCT dataset significantly reduces the doses and NTCP to OARs. PMID- 22079403 TI - Gait characteristics when walking with rounded soft sole shoes. AB - This study aimed to examine the effect of shoes with a rounded soft sole (Stretch Walker: SW) on gait. Fifteen healthy male (mean age: 23.2) walked under three conditions (SW, Flat-bottomed Shoe: FS, Barefoot: BF). Including walking speed, stance time, step length were selected as temporal-spatial parameters. The angle of hip, knee, and ankle joints during particular phases were selected as kinematic parameters. Walking speed, stance time, step length and flexion angle of the ankle joint at initial contact were greater when wearing either shoe than walking BF; cadence was faster walking BF than wearing either shoe; double support time increased (FS>SW>BF); step width was greater (FS>SW>BF); walking angle was greater wearing the SW than wearing the FS and walking BF; and range of motion and maximum flexion angle of the hip and knee joints were greater wearing the FS than walking BF. In conclusion, wearing the SW with a heel-to-toe rocker and soft sole changes the double support time, step width, and walking angle and increases step length and walking speed compared to walking BF. The difference of the range of motion in hip and knee joints was larger between walking BF and wearing the FS than between walking BF and wearing the SW. PMID- 22079404 TI - Incidence, risk factors for amputation among patients with diabetic foot ulcer in a North Indian tertiary care hospital. AB - OBJECTIVE: Aim of this study was to evaluate the incidence and risk factors for amputation among patients with diabetic foot ulcer (DFU). RESEARCH DESIGN AND METHODS: We performed a prospective study of 162 DFU in patients treated in a multidisciplinary based diabetes and endocrinology centre of Jawaharlal Nehru Medical College of Aligarh Muslim University, Aligarh, India during the period of December 2008-March 2011. Detailed history and physical examination was carried out for every subject. Risk factors for amputation were determined by univariate analysis with 95% of CI. RESULTS: The overall amputation rate was 28.4%. On univariate analysis, male sex [OR 2.8, RR 1.28], hypertension [OR 2.83, RR 1.31], neuropathy [OR 3.01, RR 1.35], nephropathy [OR 2.24, RR 1.26], LDL-C (>100mg/dl) [OR 2.53, RR 1.28], total cholesterol (>150mg/dl) [OR 3.74, RR 1.52],HDLC(<40mg/dl) [OR 1.19, RR 1.18], triglycerides (>200mg/dl) [OR 5.44, RR1.76], previous antibiotic use [OR 9.12, RR 1.92], osteomyelitis [OR 6.97, RR 2.43] and biofilm infection [OR 4.52, RR 1.41] were significant risk factors. CONCLUSION: The risk factors for amputation were presence of PVD, leukocytosis, neuropathy, nephropathy, hypertension, dyslipidemia, over use of antibiotics, osteomyelitis, biofilm production and higher grade of ulcer. PMID- 22079405 TI - Somatic mutations in aging, cancer and neurodegeneration. AB - The somatic mutation theory of aging posits that the accumulation of mutations in the genetic material of somatic cells as a function of time results in a decrease in cellular function. In particular, the accumulation of random mutations may inactivate genes that are important for the functioning of the somatic cells of various organ systems of the adult, result in a decrease in organ function. When the organ function decreases below a critical level, death occurs. A significant amount of research has shown that somatic mutations play an important role in aging and a number of age related pathologies. In this review, we explore evidence for increases in somatic nuclear mutation burden with age and the consequences for aging, cancer, and neurodegeneration. We then review evidence for increases in mitochondrial mutation burden and the consequences for dysfunction in the disease processes. PMID- 22079406 TI - Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. AB - BACKGROUND: Advanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly. METHODS: Tobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an ApoE4 allele), and kidney function. sMG was assessed by ELISA. RESULTS: The fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p = 0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and ApoE4 genotype were not significant. CONCLUSIONS: Higher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, ApoE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise. PMID- 22079407 TI - Membrane proteins in four acts: function precedes structure determination. AB - Studies on four membrane protein systems, which combine information derived from crystal structures and biophysical studies have emphasized, as a precursor to crystallization, demonstration of functional activity. These assays have relied on sensitive spectrophotometric, electrophysiological, and microbiological assays of activity to select purification procedures that lead to functional complexes and with greater likelihood to successful crystallization: (I), Hetero-oligomeric proteins involved in electron transport/proton translocation. (1) Crystal structures of the eight subunit hetero-oligomeric trans-membrane dimeric cytochrome b(6)f complex were obtained from cyanobacteria using a protocol that allowed an analysis of the structure and function of internal lipids at specific intra-membrane, intra-protein sites. Proteolysis and monomerization that inactivated the complex and prevented crystallization was minimized through the use of filamentous cyanobacterial strains that seem to have a different set of membrane-active proteases. (2) An NADPH-quinone oxido-reductase isolated from cyanobacteria contains an expanded set of 17 monotopic and polytopic hetero subunits. (II) beta-Barrel outer membrane proteins (OMPs). High resolution structures of the vitamin B(12) binding protein, BtuB, solved in meso and in surfo, provide the best example of the differences in such structures that were anticipated in the first application of the lipid cubic phase to membrane proteins [1]. A structure of the complex of BtuB with the colicin E3 and E2 receptor binding domain established a "fishing pole" model for outer membrane receptor function in cellular import of nuclease colicins. (III) A modified faster purification procedure contributed to significantly improved resolution (1.83A) of the universal porin, OmpF, the first membrane protein for which meaningful 3D crystals have been obtained [2]. A crystal structure of the N terminal translocation domain of colicin E3 complexed to OmpF established the role of OmpF as an import channel for colicin nuclease cytotoxins. (IV) alpha Synuclein, associated with the etiology of Parkinson's Disease, is an example of a protein, which is soluble and disordered in solution, but which can assume an ordered predominantly alpha-helical conformation upon binding to membranes. When subjected in its membrane-bound form to a trans-membrane electrical potential, alpha-synuclein can form voltage-gated ion channels. Summary of methods to assay functions/activities: (i) sensitive spectrophotometric assay to measure electron transfer activities; (ii) hydrophobic chromatography to deplete lipids, allowing reconstitution with specific lipids for studies on lipid-protein interactions; (iii) microbiological screen to assay high affinity binding of colicin receptor domains to Escherichia coli outer membrane receptors; (iv) electrophysiology/channel analysis (a) to select channel-occluding ligands for co crystallization with ion channels of OmpF, and (b) to provide a unique description of voltage-gated ion channels of alpha-synuclein. PMID- 22079408 TI - Microbiological and meteorological analysis of two Australian dust storms in April 2009. AB - Dust is an important source of bioaerosols including bacteria. In this study, the microbiology and meteorology of specific dust storms in Australia were investigated. The samples were collected from two dust events in April 2009 that were characterised by intense cold fronts that entrained dust from the highly erodible and drought-stricken Mallee and Riverina regions of Victoria and central NSW. In the first storm, the dust travelled eastward over Canberra and Sydney, and in the second storm, the dust travelled east/southeastward over Canberra and Melbourne. Rain fell on both cities during the second dust storm. Dust and rain samples were collected, cultured, and the composition compared using polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). Multiple bands were evident on DGGE indicative of a diverse microflora, and identification of several bands confirmed the presence of multiple genera and species representing three phyla. Numerous bands represented Bacillus species, and these were present in multiple dust samples collected from both Canberra and Melbourne. Interestingly, the microflora present in rain samples collected in Canberra during the second dust storm was quite different and the DGGE banding patterns from these samples clustered separately to most dust samples collected at the same time. Identification of several DGGE bands and PCR products from these rain samples indicated the presence of Pseudomonas species. These results indicate that Australian dust and rain have a diverse microflora and highlights the contribution of dust events to the distribution of microbes in the environment. PMID- 22079411 TI - Gamma knife radiosurgery for giant cell tumor of the petrous bone. PMID- 22079410 TI - Comparison of relative and actual chest compression depths during cardiac arrest in children, adolescents, and young adults. AB - AIM: Cardiopulmonary resuscitation (CPR) guidelines recommend specific chest compression (CC) target depths for children. We quantitatively describe relative anterior-posterior diameter (APD) depth, actual depth, and force of CCs during real CPR events in children. METHODS: CC depth and force were recorded during real CPR events in children >=8 years using FDA-approved CC sensor. Patient chest APD was measured at conclusion of each CPR event. CC data was stratified and analyzed according to age (pre-puberty, 8-14 years; post-puberty, 15+ years). Relative (% APD) and actual CC depth, corrected for mattress deflection, were assessed and compared with American Heart Association (AHA) 2005 and 2010 pediatric CPR guidelines. RESULTS: 35 events in 32 subjects included 16,158 CCs for data analysis: 16 pre-puberty (CCs=7484, age 11.9+/-2 years, APD 164.6+/-25.1 mm); 19 post-puberty (CCs=8674, age 18.0+/-2.7 years, APD 196.5+/-30.4 mm). After correction for mattress deflection, 92% of CC delivered to pre-puberty were <1/3 relative APD and 60% of CC were <38 mm actual depth. Mean actual CC depth (36.2+/ 9.6 mm vs. 36.8+/-9.9 mm, p=0.64), mean relative APD (22.5%+/-7.0% vs. 19.5+/ 6.7%, p=0.13), and mean CC force (30.7+/-7.6 kg vs. 33.6+/-9.4 kg, p=0.07) were not significantly less in pre-puberty vs. post-puberty. CONCLUSIONS: During in hospital cardiac arrest of children >=8 years, CCs delivered by resuscitation teams were frequently <1/3 relative APD and <38 mm actual depth after mattress deflection correction, below pediatric and adult target guidelines. Mean CC actual depth and force were not significantly different in pre-puberty and post puberty. Additional investigation to determine depth of CCs to optimize hemodynamics and outcomes is needed to inform future CPR guidelines. PMID- 22079412 TI - Transcriptome profiling of female alates and egg-laying queens of the Formosan subterranean termite. AB - Termites are known to have an extraordinary reproductive plasticity and capacity, but the underlying genetic patterns of termite reproductive biology are relatively understudied. The goal of this study was to identify genes for which expression levels differ between dealated precopulatory females (virgins) and egg laying queens of the Formosan subterranean termite, Coptotermes formosanus Shiraki. We constructed a normalized polyphenic expressed sequence tag (EST) library that represents genomic material from most of the castes and life stages of the Formosan subterranean termite. Microarrays were designed using probes from this EST library and public genomic resources. Virgin females and queens were competitively hybridized to these microarrays and differentially expressed candidate genes were identified. Differential expression of eight genes was subsequently confirmed via reverse transcriptase quantitative PCR (RT-QPCR). When compared to virgins, queens had higher expression of genes coding for proteins related to immunity (gram negative binding protein), nutrition (e.g., termite derived endo-beta-1,4-glucanase), protein storage, regulation of caste differentiation and reproduction (hexamerin, juvenile hormone binding protein). Queens also had higher transcript levels for genes involved in metabolism of xenobiotics, fat, and juvenile hormone (glutathione-S-transferase-like proteins, and cytochrome P450), among others. In particular, hexamerin, juvenile hormone binding protein, and a cytochrome P450 from the 4C subfamily are likely to be involved in initiating the inactive period during the reproductive cycle of the queen. Vice versa, virgins had higher expression than queens of genes related to respiration, probably due to recent flight activity, and several genes of unknown function. PMID- 22079413 TI - Insights into the pathophysiology of ankylosing spondylitis: contributions from animal models. AB - The introduction of anti-tumor necrosis factor strategies has significantly changed the perspective and outcome of patients with ankylosing spondylitis and related spondyloarthritides. This breakthrough has also boosted further research efforts into the mechanisms of disease. As human tissue specimens of the spine and sacroiliac joints are very difficult to obtain and rarely allow mechanistic studies, most of the new concepts have emerged from different animal models of disease. In this review, we summarize insights into the role of HLA-B27 based on transgenic rat and mouse models, efforts into the identification of cell populations stimulating inflammation and molecular studies of pathological bone formation leading to ankylosis. Important progress has been made and novel hypotheses were put forward. These include the impact of HLA-B27 on endoplasmic reticulum stress and the unfolded protein response, the role of stromal cells in inflammation, the entheseal stress hypothesis and the identification of the bone morphogenetic protein and WNT signaling pathways as therapeutic targets for ankylosis. PMID- 22079415 TI - Bone tissue and muscle dystrophin deficiency in mdx mice. AB - Duchenne muscular dystrophy is a neuromuscular disease caused by the lack of dystrophin that affects skeletal muscles, causing degeneration of muscle fibers and replacing them with fibrous and adipose tissue, events that gradually lead to functional loss. Patients with Duchenne muscular dystrophy have shown that bones become more fragile with age and with advancement of the disease. Muscle weakness and reduced mobility have been suggested to be the factors that promote bone deterioration. However, it seems that this does not occur in mdx mice. It has been identified in mdx mice the existence of a factor related or not to the lack of dystrophin that also participates in the impairment of bone quality. Mdx mice also exhibit muscle degeneration, but unlike human, it is compensated by muscle regeneration. In consequence, there is an increase in the muscle mass, but not necessarily of muscle contractile strength. The accommodation of this increased muscle mass promotes bone formation at specific sites, such as at tendo-osseous junctions. In addition, the inflammatory response to muscle injury may be responsible for the increase in angiogenesis and regeneration observed in mdx mice, inducing the release of cytokines and chemokines that play an important role in the recruitment of leukocytes and macrophages. Then, mdx mice may possess compensatory mechanisms in bone in response to a genetic defect. PMID- 22079417 TI - Disease associated cytokine SNPs database: an annotation and dissemination model. AB - Cytokines mediate crucial functions in innate and adaptive immunity. They play valuable roles in immune cell growth and lineage specification, and are associated with various disease pathologies. A large number of low, medium and high throughput studies have implicated association of single nucleotide polymorphisms (SNPs) in cytokine genes with diseases. A preponderance of such experiments has not shown any causality of an identified SNP to the associated disease. Instead, they have identified statistically significant SNP-disease associations; it is likely that some of these cytokine gene variants may directly or indirectly cause the disease phenotype(s). To fill this knowledge gap and derive study parameters for cytokine SNP-disease causality relationships, we have designed and developed the disease associated cytokine SNP database (DACS-DB). DACS-DB has data on 456 cytokine genes, approximately 63,000 SNPs, and 853 SNP associated diseases. In DACS-DB, among other attributes, we present functional annotation, and heterozygosity allele frequency for the SNPs, and literature validated SNP association for diseases. Users of the DB can run queries such as the ones to find disease-associated SNPs in a cytokine gene, and all the SNPs involved in a disease. We have developed a web front end (available at http://www.iupui.edu/~cytosnp) to disseminate this information for immunologists, biomedical researchers, and other interested biological researchers. Since there is no such comprehensive collection of disease associated cytokine SNPs, this DB will be vital to understand the role of cytokine SNPs as markers in disease, and more importantly, in causality to disease thus helping to identify drug targets for common inflammatory diseases. PMID- 22079418 TI - Identification, organ expression and ligand-dependent expression levels of peroxisome proliferator activated receptors in grass carp (Ctenopharyngodon idella). AB - The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor family, and can regulate various genes involved in lipid metabolism. The aim of the present study was to investigate the tissue distribution patterns of PPARs and their ligand specificities in grass carp. We cloned three PPAR isotypes of the species and evaluated their organ distribution patterns using real-time PCR. Through analyzing the deduced amino acid sequences identities between the products cloned in grass carp and those described in other species, we concluded that the same type of PPAR amino acid sequences in different species were with high homology, and different subtypes of PPAR in the same species were with low homology. The mRNA constitutive expression level of PPARalpha predominated in the liver, but was weak in other tested tissues. PPARbeta was present in all tested organs, and particularly abundant in heart, liver and muscle. PPARgamma was only detected in the liver, and to a lesser extent in brain, muscle and visceral adipose tissue. Grass carp were intraperitoneally injected with 50 mg kg(-1) body mass (bw) dose of clofibrate, 42 mg kg(-1) bw dose of 2-bromo palmitate and 1 mg kg(-1) bw dose of 15-deoxy-Delta(12,14) prostaglandin J2 (15d-PGJ2), respectively, and the relative changes of the mRNA abundance of PPARs in liver were analyzed by real time PCR. Clofibrate was able to increase the expressions of both PPARalpha and beta, but was not able to for PPARgamma. 2-bromo palmitate could affect the expressions of both PPARbeta and gamma, but was not able to for PPARalpha. 15d PGJ2 was able to induce PPARbeta expression, but PPARalpha and gamma were not enhanced. Consequently, these results indicate that clofibrate, 2-bromo palmitate and 15d-PGJ2 could be applied as the activators of grass carp PPARs. PMID- 22079420 TI - [Ocular syphilis. A report of two patients]. AB - INTRODUCTION: Whereas syphilis is a classical cause of uveitis, it is still often under-recognized. Treatment recommendations are not based on specific clinical studies. CASE REPORTS: We report two patients with syphilitic uveitis diagnosed and treated at the University Hospital of Angers. Ocular involvement was inaugural in both patients. Each had a specific treatment but none had a complete recovery of visual function. CONCLUSION: Syphilis must be discussed in all patients diagnosed with uveitis or papillitis. Although not evidence-based, prompt therapy may lead to functional recovery. PMID- 22079416 TI - Neurodegeneration the RNA way. AB - The expression, processing, transport and activities of both coding and non coding RNAs play critical roles in normal neuronal function and differentiation. Over the past decade, these same pathways have come under scrutiny as potential contributors to neurodegenerative disease. Here we focus broadly on the roles of RNA and RNA processing in neurodegeneration. We first discuss a set of "RNAopathies", where non-coding repeat expansions drive pathogenesis through a surprisingly diverse set of mechanisms. We next explore an emerging class of "RNA binding proteinopathies" where redistribution and aggregation of the RNA binding proteins TDP-43 or FUS contribute to a potentially broad range of neurodegenerative disorders. Lastly, we delve into the potential contributions of alterations in both short and long non-coding RNAs to neurodegenerative illness. PMID- 22079419 TI - Estimating the transmission potential of supercritical processes based on the final size distribution of minor outbreaks. AB - Use of the final size distribution of minor outbreaks for the estimation of the reproduction numbers of supercritical epidemic processes has yet to be considered. We used a branching process model to derive the final size distribution of minor outbreaks, assuming a reproduction number above unity, and applying the method to final size data for pneumonic plague. Pneumonic plague is a rare disease with only one documented major epidemic in a spatially limited setting. Because the final size distribution of a minor outbreak needs to be normalized by the probability of extinction, we assume that the dispersion parameter (k) of the negative-binomial offspring distribution is known, and examine the sensitivity of the reproduction number to variation in dispersion. Assuming a geometric offspring distribution with k=1, the reproduction number was estimated at 1.16 (95% confidence interval: 0.97-1.38). When less dispersed with k=2, the maximum likelihood estimate of the reproduction number was 1.14. These estimates agreed with those published from transmission network analysis, indicating that the human-to-human transmission potential of the pneumonic plague is not very high. Given only minor outbreaks, transmission potential is not sufficiently assessed by directly counting the number of offspring. Since the absence of a major epidemic does not guarantee a subcritical process, the proposed method allows us to conservatively regard epidemic data from minor outbreaks as supercritical, and yield estimates of threshold values above unity. PMID- 22079421 TI - [Autoimmune channelopathies]. AB - Autoimmune channelopathies are rare neuromuscular diseases that have been characterized clinically for several decades but for which the evidence of associated antibodies has only been recently demonstrated. Ion channels have an important role of activation, inhibition and regulation in neuromuscular transmission. Myasthenia gravis, generally associated with the presence of anti acetylcholine receptor antibody, is the best-known channelopathy. Other anti channel antibodies, including voltage-dependent, are associated with several neurological diseases, as illustrated by anti-voltage-gated calcium channels found in Lambert-Eaton myasthenic syndrome and paraneoplastic cerebellar ataxia, and anti-voltage-gated potassium channels found in neuromyotonia, Morvan's syndrome and limbic encephalitis. The treatment of autoimmune channelopathies is logically based on corticosteroids, immunosuppressant drugs, intravenous immunoglobulins and plasmapheresis. PMID- 22079422 TI - [From HLA to cell therapy]. PMID- 22079423 TI - Spatio-temporal epidemiology of highly pathogenic avian influenza (H5N1) outbreaks in Nigeria, 2006-2008. AB - From 2006 to 2008, outbreaks of highly pathogenic avian influenza A (HPAI) virus of the H5N1 subtype occurred among poultry in Nigeria. We described the spatio temporal patterns of the HPAI H5N1 outbreaks in Nigeria. Data of suspected and laboratory confirmed outbreaks maintained at the National Veterinary Research Institute Vom was analyzed using descriptive and exploratory analyses, GIS mapping, global and local spatial statistical analyses using the Cuzick-Edwards' (C-E) test and SaTScan Space-Time Scan Statistic. A total of 1654 suspected outbreaks were reported from 32 of the 36 States and the Federal Capital Territory (FCT), 299 were confirmed HPAI H5N1 positive from 27 states and FCT. The outbreaks occurred as three distinct epidemic waves with peak periods of January-March mainly in the North-West, North-Central and North-East regions during 2006 and 2007 and July-September in the South-West and South-South regions in 2007. Three spatio-temporal clusters were identified extending across States and international borders, consistent with disease transmission occurring through local and long-distance spread. This calls for enhanced strategies by the states and regional authorities to improve surveillance, prevention and control measures at the states, national and international levels. PMID- 22079424 TI - The inhibitory potency of local anesthetics on NMDA receptor signalling depends on their structural features. AB - Development of postoperative hyperalgesia depends on N-methyl-d-aspartate (NMDA) receptor activation. Local anesthetics protect against those hyperalgesic pain states and inhibit NMDA receptor activation. To outline what structural features of local anesthetics are responsible for NMDA receptor inhibition we evaluated a series of experimental lidocaine analogs (carbanilic derivates). Human GluN1/GluN2A NMDA receptors were expressed recombinantly in Xenopus laevis oocytes. Peak currents were measured by voltage clamp technique. Oocytes were stimulated with glutamate/glycine (EC(50)). The responses following a 10min incubation with in total 13 experimental derivates of local anesthetics (10(-3)M 10(-7)M) were measured to obtain the IC(50). Furthermore the Comprehensive Descriptors for Structural and Statistical Analysis CODESSA software was used to design a Quantitative Structure-Activity Relationship (QSAR)-model for all substances. The IC(50) values were in the range of 2.74*10(-5)M-2.26*10(-3)M, strongly affected by the position and the length of the aliphatic side chain in the aromatic part of the local anesthetic molecule. Substance with no substituent on the aromatic ring showed the highest inhibitory activity. The obtained QSAR model predicted that lidocaine derivatives with free positions 2 and 6 on the aromatic ring had a higher efficacy than clinically used local anesthetics for inhibition of NMDA receptor signaling. Structural changes of local anesthetic molecules can alter the potency to inhibit NMDA receptor signaling and are independent of the local anesthetic (sodium-channel blocking) potency. The development of novel drugs based on local anesthetic like structures may be a new approach for the protection or treatment of NMDA receptor mediated hyperalgesia and may be associated with a low side effect profile. PMID- 22079425 TI - A Vegetation Index qualifying pasture edges is related to Ixodes ricinus density and to Babesia divergens seroprevalence in dairy cattle herds. AB - Babesia divergens, transmitted by the tick Ixodes ricinus, is the main agent of bovine piroplasmosis in France. This Apicomplexa often is present in asymptomatic carriers; however, clinical cases are rare. While numerous factors are known to influence tick density, no risk factor of contact with B. divergens has been identified for cattle. Our study aimed to explore whether a Vegetation Index could serve as an indirect indicator of within-herd B. divergens seroprevalence. In February 2007, blood samples were taken from all of the cows in 19 dairy cattle herds in Western France and IFAT serology was performed individually to measure B. divergens seroprevalence. The following spring, I. ricinus nymphs were collected by drag sampling along transects on the vegetation of each farm's pasture perimeters. Tick density was related significantly to a Vegetation Index (V.I., ranging from 1 to 5) that took into account the abundance of trees and bushes on the edge of pastures: most ticks (57%) were found in transects with the highest V.I. (covering 15% of the explored surface in the study area). At the farm level, the proportion of transects presenting I. ricinus nymphs was significantly related to B. divergens seroprevalence: the farms with more than 15% of transects with I. ricinus had a significantly higher risk of high seroprevalence. The proportion of pasture perimeters where the V.I.=5 also was significantly related to B. divergens seroprevalence: the farms where more than 20% of transects had a V.I.=5 had a significantly higher risk of high seroprevalence. Given that the Vegetation Index is a steady indicator of the potential I. ricinus density in the biotope, we recommend that the risk of high B. divergens seroprevalence in cows be evaluated using this tool rather than drag samplings. PMID- 22079426 TI - Levels of some antioxidant molecules and lipid peroxidation during in vivo transformation of the progenetic metacercaria of Clinostomum complanatum to ovigerous adult worms. AB - The levels of oxidative stress markers are an important indicator of the physiological state of the parasite and its host. In the present study levels of lipid peroxidation, glutathione S transferase, glutathione, superoxide dismutase and catalase were determined in the Clinostomum complanatum progenetic metacercaria, obtained from the fish peritoneum (a hypoxic habitat). The in vivo transformed ovigerous adult worms were obtained from the aerobic environment of the buccopharyngeal region of experimentally infected chickens. Levels of antioxidant molecules were also determined in the blood of experimentally infected chickens. An increase in the levels of lipid peroxidation, and a significant decrease in the levels of glutathione S transferase, glutathione, superoxide dismutase and catalase was observed in the infected host as compared to the controls. In the ovigerous worms, the levels of lipid peroxidation, glutathione S transferase, glutathione, superoxide dismutase were found to be significantly less than the levels observed in the progenetic metacercaria. Since the establishment of worm in the buccal cavity of the avian host would lead to its exposure to oxygen and the haematophagous nature of the parasite also exposes it to the free radicals in the host blood, the progenetic metacercaria has evolved to produce excess free radical scavenging molecules reserved to combat the oxidative stress encountered within the microhabitat of the definitive host. PMID- 22079427 TI - A respiratory syncytial virus isolate enables the testing of virucidal products. AB - The respiratory syncytial virus (RSV) is known as a major cause of respiratory infections and nosocomial diseases. Testing this virus is rather difficult due to the problems encountered in producing it at a high titer without using any purification method. A RSV isolate which replicates to high level on a Hep-2 cell line with an infectious titer of at least 10(7)TCID(50)mL(-1) in culture supernatant fluids has been identified. Thanks to this isolate, the virucidal effects of two products, a hand rub solution and a surface disinfectant, were conveniently tested according to the EN 14476:2007-02 procedure. PMID- 22079428 TI - Absence of mannose-binding lectin prevents hyperglycemic cardiovascular complications. AB - Diabetes, stress, pharmaceuticals, surgery, and physical trauma can lead to hyperglycemic conditions. A consistent relationship has been found between chronic inflammation and the cardiovascular complications of hyperglycemia. We hypothesized that cardiomyopathy and vasculopathy resulting from acute hyperglycemia are dependent on mannose-binding lectin (MBL) and lectin complement pathway activation. Hyperglycemia was induced in wild-type (WT) C57BL/6 and MBL null mice after streptozotocin administration. Echocardiographic data and tissue samples were collected after 4, 7, or 14 days of acute hyperglycemia. Hyperglycemic WT mice demonstrated dilated cardiomyopathy with significantly increased short and long axis area measurements during systole and diastole compared to hyperglycemic MBL-null mice. The EC(50) for acetylcholine-induced relaxation of mesenteric arterioles in WT mice after 4 days of hyperglycemia demonstrated a significant loss of nitric oxide-mediated relaxation compared to normoglycemic WT or hyperglycemic MBL-null mice. Myocardial histochemistry and Western blot analysis revealed a significant influx of macrophages, altered morphology, and increased elastin and collagen deposition in hyperglycemic WT hearts compared to MBL-null hearts. Serum transforming growth factor-beta1 levels were significantly lower in hyperglycemic MBL-null compared to WT mice, suggesting decreased profibrotic signaling. Together, these data suggest that MBL and the lectin complement pathway play a significant role in vascular dysfunction and cardiomyopathy after acute hyperglycemia. PMID- 22079429 TI - Elastase/LPS-exposed mice exhibit impaired innate immune responses to bacterial challenge: role of scavenger receptor A. AB - Nontypeable Haemophilus influenzae (NTHi) is an important bacterial pathogen associated with lower respiratory tract colonization and with acute exacerbations and disease progression in chronic obstructive pulmonary disease (COPD). Why the immune system fails to eliminate NTHi and the exact contribution of the organism to COPD progression are not well understood, in part because we lack an animal model that mimics all aspects of COPD. For this study, we used an established murine model that exhibits typical features of COPD. Elastase/LPS-exposed mice infected with NTHi showed persistence of bacteria up to 5 days after infection, whereas mice exposed to elastase, LPS, or PBS cleared all bacteria by 3 days. Elastase/LPS-exposed mice also showed sustained lung neutrophilic inflammation, goblet cell metaplasia, airway hyperresponsiveness, and progression of emphysema at 15 days after infection. Alveolar macrophages isolated from elastase/LPS exposed mice showed impaired bacterial phagocytosis, reduced expression of MARCO and of mannose receptor, and absent expression of scavenger receptor-A (SR-A). Neutralization of SR-A significantly decreased phagocytosis of NTHi by normal alveolar macrophages. Our results suggest that elastase/LPS-exposed mice show impaired bacterial clearance and sustained lung inflammation. Lack of SR-A expression may, in part, be responsible for impaired phagocytosis of bacteria by alveolar macrophages of elastase/LPS-exposed mice. These data validate the suitability of elastase/LPS model for investigating NTHi pathogenesis and progression of disease in COPD. PMID- 22079430 TI - Platelet-activating factor receptor is essential for the development of experimental cerebral malaria. AB - Cerebral malaria is a severe form of the disease that may result, in part, from an overt inflammatory response during infection by Plasmodium falciparum. The understanding of the pathogenesis of cerebral malaria may aid in the development of better therapeutic strategies for patients. The immune response in cerebral malaria involves elevation of circulating levels of cytokines and chemokines associated with leukocyte accumulation and breakdown of the blood-brain barrier in the central nervous system. Platelet-activating factor (PAF) is a mediator of inflammation shown to orchestrate inflammatory processes, including recruitment of leukocytes and increase of vascular permeability. Using mice lacking the PAF receptor (PAFR(-/-)), we investigated the relevance of this molecule for the outcome and the neuroinflammatory process triggered by P. berghei ANKA, an experimental model of cerebral malaria. In PAFR(-/-) mice, lethality was markedly delayed and brain inflammation was significantly reduced, as demonstrated by histology, accumulation, and activation of CD8(+) T cells, changes in vascular permeability and activation of caspase-3 on endothelial cells and leukocytes. Similarly, treatment with the PAFR antagonist UK-74,505 delayed lethality. Taken together, the results suggest that PAFR signaling is crucial for the development of experimental cerebral malaria. Mechanistically, PAFR activation is crucial for the cascade of events leading to changes in vascular permeability, accumulation, and activation of CD8(+) T cells and apoptosis of leukocytes and endothelial cells. PMID- 22079432 TI - Renal dendritic cells adopt a pro-inflammatory phenotype in obstructive uropathy to activate T cells but do not directly contribute to fibrosis. AB - Unilateral ureteral obstruction (UUO) is a well-characterized murine model of renal inflammation leading to fibrosis. Renal dendritic cells (DCs) constitute a significant portion of kidney leukocytes and may participate in local inflammation and have critical roles in antigen presentation. The heterogeneity in renal DC populations and surface marker overlap with monocytes/macrophages has made studying renal DCs difficult. These studies used CD11c-promoter driven reporter/depletion mice to study DCs in vivo. Studying early local inflammatory events (day 3 of UUO), in vivo multiphoton imaging of the intact kidney of CD11c reporter mice revealed more dendrite extensions and increased activity of renal DCs in real time. Phenotypic analysis suggested resident DC maturation in obstructed kidneys with increased CD11b and less F4/80 expressed. CD11b(hi) Gr 1(+) inflammatory DCs were also present in obstructed kidneys. T-cell receptor transgenic mice revealed enhanced antigen-presenting capacity of renal DCs after UUO, with increased antigen-specific T-cell proliferation in vivo and ex vivo. However, conditional DC ablation at days 0, 2, or 4 did not attenuate fibrosis or apoptosis 7 days after UUO, and depletion at 7 days did not alter outcomes at day 14. Therefore, after UUO, renal DCs exhibit inflammatory morphological and functional characteristics and are more effective antigen-presenting cells, but they do not directly contribute to tubulointerstitial damage and fibrosis. PMID- 22079431 TI - Minor histocompatibility antigens are expressed in syncytiotrophoblast and trophoblast debris: implications for maternal alloreactivity to the fetus. AB - The fetal semi-allograft can induce expansion and tolerance of antigen-specific maternal T and B cells through paternally inherited major histocompatibility complex and minor histocompatibility antigens (mHAgs). The effects of these antigens have important consequences on the maternal immune system both during and long after pregnancy. Herein, we investigate the possibility that the placental syncytiotrophoblast and deported trophoblastic debris serve as sources of fetal mHAgs. We mapped the expression of four mHAgs (human mHAg 1, pumilio domain-containing protein KIAA0020, B-cell lymphoma 2-related protein A1, and ribosomal protein S4, Y linked) in the placenta. Each of these proteins was expressed in several placental cell types, including the syncytiotrophoblast. These antigens and two additional Y chromosome-encoded antigens [DEAD box polypeptide 3, Y linked (DDX3Y), and lysine demethylase5D] were also identified by RT-PCR in the placenta, purified trophoblast cells, and cord blood cells. Finally, we used a proteomic approach to investigate the presence of mHAgs in the syncytiotrophoblast and trophoblast debris shed from first-trimester placenta. By this method, four antigens (DDX3Y; ribosomal protein S4, Y linked; solute carrier 1A5; and signal sequence receptor 1) were found in the syncytiotrophoblast, and one antigen (DDX3Y) was found in shed trophoblast debris. The finding of mHAgs in the placenta and in trophoblast debris provides the first direct evidence that fetal antigens are present in debris shed from the human placenta. The data, thus, suggest a mechanism by which the maternal immune system is exposed to fetal alloantigens, possibly explaining the relationship between parity and graft versus-host disease. PMID- 22079433 TI - Melatonin inhibits glucocorticoid-dependent GR-TIF2 interaction in newborn hamster kidney (BHK) cells. AB - The antagonism exerted by melatonin on the glucocorticoid response has been well established, being strongly dependent on the cellular context. Previously, we found that melatonin inhibits glucocorticoid receptor (GR) dissociation from the chaperone hetero-complex and nuclear translocation on mouse thymocytes. Here, by performing confocal fluorescence microscopy and the Number and Brightness assay we show that in newborn hamster kidney cells (BHK21) melatonin neither affects GR nuclear translocation nor GR homodimerization. Instead, co-immunoprecipitation studies suggest that physiological concentrations of melatonin impair GR interaction with the transcriptional intermediary factor 2 (TIF2). This melatonin effect was not blocked by the MT(1)/MT(2) receptor antagonist luzindole. Curiously, luzindole behaved as an antiglucocorticoid per se by impairing the glucocorticoid-dependent MMTV-driven gene expression affecting neither GR translocation nor GR-TIF2 interaction. PMID- 22079434 TI - Stimulation of inflammatory gene expression in human preadipocytes by macrophage conditioned medium: upregulation of IL-6 production by macrophage-derived IL 1beta. AB - The aim of this study was to examine the effects of macrophage secretions on global gene expression in human preadipocytes using microarrays. Preadipocytes were cultured with unconditioned or conditioned medium from U937 macrophages, and gene expression examined with Agilent arrays (43,000 probes). 472 transcripts were differentially regulated (>2-fold difference; P<0.05) between preadipocytes in the conditioned medium compared to the unconditioned; 401 were upregulated and 71 downregulated. The upregulated transcripts were particularly linked to inflammation, including IL-1beta, IL-6, and CCL20 (16.8-, 10.0-, and 8.9-fold increases, respectively) together with matrix metalloproteinases (MMP3, MMP9 and MMP12). Major pathways regulated by the conditioned medium were linked to inflammation, macrophage infiltration and lipid accumulation. Network analysis identified NFkB and IL-1beta as central nodes in the upregulation of multiple inflammation-related genes. Treatment with an IL-1beta neutralising antibody abolished the stimulation of IL-6 secretion by conditioned medium, indicating that IL-1beta is a key regulator of preadipocyte IL-6 production. Macrophages evoke extensive changes in preadipocyte gene expression. PMID- 22079435 TI - The era of systems developmental biology. PMID- 22079436 TI - Ictal headache: headache as first ictal symptom in focal epilepsy. AB - Headache may be associated with seizures as a preictal, ictal, or postictal phenomenon, but it is often neglected because of the dramatic neurological manifestations of the seizure. Headache can also be the sole or predominant clinical manifestation of epileptic seizures, although this is a relatively rare condition. We describe two cases of focal symptomatic drug-resistant epilepsy with headache as the first ictal symptom. In both cases, the headache, which lasted a few seconds, was contralateral to the ictal discharge and did not have the clinical features of migraine. Ictal headache is a rare epilepsy symptom that can help to localize ictal EEG discharges. Recently, the term ictal epileptic headache has been proposed in cases in which headache is the sole ictal epileptic manifestation Diagnosis requires the simultaneous onset of headache with EEG demonstrated ictal discharges. PMID- 22079437 TI - Prevalence of autism-caused disability among Chinese children: a national population-based survey. AB - Few articles in English have discussed the prevalence of autism in China. The work described here was aimed at estimating the prevalence rate of autism-caused disability among Chinese children and exploring family environmental factors associated with autism based on a national population sample. Data for this study were derived from the Second China National Sample Survey on Disability. A weighted number of 77,301 disabled children affected by autism were identified, yielding a prevalence rate of 2.38/10,000. A history of mental disorders in adults was strongly associated with autism. The prevalence of autism in Chinese children was underestimated, and the lack of qualified professionals able to identify and diagnose autism was the main reason. Countermeasures are warranted to obtain a more precise overview of autism in China. PMID- 22079438 TI - What makes a simple partial seizure complex? AB - The assessment of ictal consciousness has been the landmark criterion for the differentiation between simple and complex partial seizures over the last three decades. After review of the historical development of the concept of "complex partial seizure," the difficulties surrounding the simple versus complex dichotomy are addressed from theoretical, phenomenological, and neurophysiological standpoints. With respect to consciousness, careful analysis of ictal semiology shows that both the general level of vigilance and the specific contents of the conscious state can be selectively involved during partial seizures. Moreover, recent neuroimaging findings, coupled with classic electrophysiological studies, suggest that the neural substrate of ictal alterations of consciousness is twofold: focal hyperactivity in the limbic structures generates the complex psychic phenomena responsible for the altered contents of consciousness, and secondary disruption of the network involving the thalamus and the frontoparietal association cortices affects the level of awareness. These data, along with the localization information they provide, should be taken into account in the formulation of new criteria for the classification of seizures with focal onset. PMID- 22079439 TI - R-Isovaline: a subtype-specific agonist at GABA(B)-receptors? AB - The R-enantiomer of isovaline, an analgesic amino acid, has a chemical structure similar to glycine and GABA. Although its actions on thalamic neurons are strychnine-resistant and independent of the Cl(-) gradient, R-isovaline increases membrane conductance for K(+). The purpose of this study was to determine if R isovaline activated metabotropic GABA(B) receptors. We used whole-cell voltage clamp recordings to characterize the effects of R-isovaline applied by bath perfusion and local ejection from a micropipette to thalamic neurons in 250 MUm thick slices of rat brain. The immunocytochemical methods that we employed to visualize GABA(B1) and GABA(B2) receptor subunits showed extensive staining for both subunits in ventrobasal nuclei, which were the recording sites. Bath or local application of R-isovaline caused a slowly developing increase in conductance and outward rectification in 70% (54/77) of neurons, both effects reversing near the K(+) Nernst potential. As with the GABA(B) agonist baclofen, G proteins likely mediated the R-isovaline effects because they were susceptible to blockade by non-hydrolyzable substrates of guanosine triphosphate. The GABA(B) antagonists CGP35348 and CGP52432 prevented the conductance increase induced by R isovaline, applied by bath or local ejection. The GABA(B) allosteric modulator CGP7930 enhanced the R-isovaline induced increase in conductance. At high doses, antagonists of GABA(A), GABA(C), glycine(A), MU-opioid, and nicotinic receptors did not block R-isovaline responses. The observations establish that R-isovaline increases the conductance of K(+) channels coupled to metabotropic GABA(B) receptors. Remarkably, not all neurons that were responsive to baclofen responded to R-isovaline. The R-isovaline-induced currents outlasted the fast baclofen responses and persisted for a 1-2-h period. Despite some similar actions, R isovaline and baclofen do not act at identical GABA(B) receptor sites. The binding of R-isovaline and baclofen to the GABA(B) receptor may not induce the same conformational changes in receptor proteins or components of the intracellular signaling pathways. PMID- 22079440 TI - Somatotopic direct projections from orofacial areas of primary somatosensory cortex to pons and medulla, especially to trigeminal sensory nuclear complex, in rats. AB - The primary somatosensory cortex (S1) projects to the thalamus and brainstem somatosensory nuclei and modulates somatosensory information ascending to the S1 itself. However, the projections from the S1 to the brainstem second-order somatosensory neuron pools have not been fully studied. To address this in rats, we first revealed the somatotopic representation of orofacial areas in the S1 by recording cortical surface potentials evoked by stimulation of the lingual, mental, infraorbital, and frontal nerves. We then examined the morphology of descending projections from the electrophysiologically defined orofacial S1 areas to the pons and medulla after injections of an anterograde tracer, biotinylated dextranamine (BDA), into the orofacial S1 areas. BDA-labeled axon terminals were seen mostly in the trigeminal sensory nuclear complex (TSNC) and had a strong contralateral predominance. They also showed a somatotopic arrangement in dorsoventral and superficial-deep directions within almost all rostrocaudal TSNC levels, and in a rostrocaudal direction within the trigeminal caudal subnucleus. In the principal nucleus (Vp) or oral subnucleus (Vo) of TSNC, the BDA-labeled axon terminals showed a somatotopic arrangement closely matched to that of the electrophysiologically defined projection sites of orofacial primary afferents; these projection sites were marked by injections of a retrograde tracer, Fluorogold (FG), into the Vp or Vo. The FG injections labeled a large number of S1 neurons, with a strong contralateral predominance, in a somatotopic manner, which corresponded to that presented in the electrophysiologically defined orofacial S1 areas. The present results suggest that the orofacial S1 projections to somatotopically matched regions of trigeminal second-order somatosensory neuron pools may allow the orofacial S1 to accurately modulate orofacial somatosensory transmission to higher brain centers including the orofacial S1 itself. PMID- 22079441 TI - A massive basal cell adenocarcinoma of the palatal minor salivary gland that progressed into the pterygopalatine fossa. AB - Basal cell adenocarcinoma (BCAC) is a rare malignant neoplasm in the salivary glands and BCAC of the minor salivary glands is exceedingly rare. Only nine cases of palatal BCACs of the minor salivary gland have been reported. BCAC is a low grade malignant tumour which shares many histologic characteristics with basal cell adenoma. Histological differentiation between the two is difficult and they are often discriminated only by invasion of local structures or by perineural or vascular invasive figures. The authors describe the case of a 69-year-old man with a massive BCAC of a palatal minor salivary gland that progressed into the nasal cavity and pterygopalatine fossa and was treated by a subtotal maxillectomy. This is a highly locally advanced case which required a wider surgical excision range than other previously reported BCAC cases of the palatal minor salivary glands. In this case, the proper diagnosis could not be made by local biopsy alone. It should be kept in mind that it may be difficult to distinguish BCAC from basal cell adenoma by microscopic examination of biopsy specimens alone. PMID- 22079442 TI - Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and neuropsychological status among older adults in New York. AB - Polybrominated diphenyl ethers (PBDEs) are emerging environmental contaminants, but little is known about their possible human health effects. The objective of this study is to evaluate the association between exposure to PBDEs and neuropsychological function among older adults and the possibility of effect modification with polychlorinated biphenyls (PCBs). Serum samples were analyzed for concentrations of 9 PBDE and 30 PCB congeners and 34 tests of cognitive and motor function, affective state, and olfactory function were assessed among 144 men and women of 55-74 years of age. After adjustment for relevant confounders, no overall associations were observed between the sum of the PBDE congener concentrations in serum (? PBDE) and scores on the neuropsychological tests. However, statistically significant interactions were found between PBDEs and PCBs for some measures of verbal learning and memory. Among persons with ? PCB concentrations at or above the median of 467ppb (lipid basis), an increase in ? PBDE concentrations from the 25th to 75th percentile was associated with decreases between 7% and 12% on scores for certain subscales of the California Verbal Learning Test. In contrast, no statistically significant associations were observed for PBDEs among persons with ? PCB levels below the median. The results suggest that PBDEs and PCBs may interact to affect verbal memory and learning among persons 55-74 years old. This is the first study to evaluate the neuropsychological effects of PBDEs in adults and the possibility of synergy with PCBs in humans. PMID- 22079443 TI - Thrombin generation in clinical conditions. AB - Commercial assays for determining thrombin generation in plasma are being tested in clinical conditions associated with thrombosis or bleeding. While pre analytical conditions remain a source of inter laboratory variation, demanding for further standardization, clinical research proceeds. In patients at risk of venous thrombosis thrombin generation (TG) analysis may be utilized to detect underlying thrombophilia and this has been achieved both with addition of thrombomodulin or activated protein C, to test the contribution of the protein C system. In patients with documented venous thromboembolism, increased TG values are seen in those patients at greatest risk for recurrence, although the data are not consistent yet. In patients with arterial vascular disease, effects on TG patterns are seen that both reflect atherosclerosis (and its risk factors) and link to risk of recurrent atherothrombosis (coronary or stroke), but the data are limited. In patients with a bleeding diathesis, like hemophilia, the main importance of TG assays lies in the application for monitoring replacement therapy, either with factor concentrate or rFVIIa. An interesting application is in conjunction with thromboelastography, for monitoring peri-operative transfusion policy. Finally, TG analysis may contribute to monitoring anticoagulant drug treatment, but these and other applications would greatly benefit from whole blood, point of care applications of TG testing. PMID- 22079445 TI - Liporetro-D-peptides - a novel class of highly selective thrombin inhibitors. AB - INTRODUCTION: Plasma serine protease thrombin plays a key role in coagulation, haemostasis and thromboembolic diseases. Direct thrombin inhibitors could be beneficial for future anticoagulant therapy. We have synthesized and studied liporetro-D-peptides - efficient thrombin inhibitors resistant to enzymatic degradation. MATERIALS AND METHODS: Compounds X-D-Arg-D-Phe-OMe, where X=residue of lauric or myristic acid or 9-fluorenylmethoxycarbonyl, have been synthesized by conventional peptide synthesis in solution and their comparative inhibitory analysis in relation to thrombin, factor X, plasmin and trypsin has been conducted. RESULTS: Modification of the synthetic liporetro-D-peptides with the myristic acid residue was the most successful one. This modification has dramatically increased the inhibition efficacy (Ki=0,17 MUM) and selectivity toward the chosen target enzyme, thrombin, in comparison to factor X, plasmin and trypsin (more than 600, 900, and 5000-fold, respectively). CONCLUSIONS: Our findings establish an important role of the fatty moiety in the structure of peptide inhibitors with regards to their potency and selectivity toward thrombin. PMID- 22079444 TI - Controlled reperfusion with intravenous bivalirudin and intracoronary abciximab combination therapy in the porcine myocardial infarction model. AB - INTRODUCTION: The reperfusion injury (RI) remains a significant limitation of primary PCI, therefore we evaluated the role of intracoronary abciximab and bivalirudin for anticoagulation on myocardial salvage and RI in the porcine model of ischemia/reperfusion. MATERIALS AND METHODS: Myocardial infarction was induced in 23 pigs by 60-minute over-the-wire (OTW) balloon occlusion of the LAD. Animals received intravenous bivalirudin and then five minutes prior to reperfusion, either a coronary downstream infusion of abciximab (n=11) or saline (n=12) through the central lumen of an OTW catheter. All animals were followed for 48 hours. RESULTS: Histological analysis showed that infarct area (IA) and area at risk (AAR) were comparable between groups (IA/AAR%: 57.6 +/- 8% vs. 57.1 +/- 7%, p=0.8). Confirming this trend, biochemical markers (troponin I, TNF-alpha, IL-6, hsCRP, adiponectin, and VCAM) and left ventricular ejection fraction were also similar at 48 hours. Adhesion markers like ICAM and P-selectin were significantly decreased in the study group, nevertheless histological evidence of leukocyte extravasation was similar. The enhancement of apoptosis by TUNEL was comparable in both groups. The number of hemorrhagic infarctions confirmed by micro and macroscopic evaluation tended to be higher in the study group (70% vs. 20%, p=0.07). CONCLUSIONS: Despite lowered concentrations of adhesion molecules, intracoronary abciximab with peripheral bivalirudin is not superior to bivalirudin unaided in terms of myocardial salvage caused by RI in the porcine ischemia/reperfusion model. This might be due to local hemorrhage caused by abciximab. PMID- 22079446 TI - Evaluation of the procoagulant activity of endogenous phospholipids in the platelet-free plasma of children with sickle cell disease using functional assays. AB - BACKGROUND: The mechanisms of hypercoagulability in sickle cell disease (SCD) are poorly understood. OBJECTIVE: We aimed to explore the procoagulant activity of endogenous phospholipids (ePL) in the platelet-free plasma of SCD children. METHODS: A factor Xa clotting time (XACT), thrombin generation (TG) and a capture based assay for the detection of procoagulant microparticles (PMP) were used. Forty three SCD children (35 SS, 6 SC and 2 Sbeta+) were evaluated at steady state and compared to 20 controls. Fourteen patients were also evaluated during vaso-occlusive crisis. TG was performed using 10 pM tissue factor without addition of exogenous phospholipids. A control condition was also performed using 10 pM tissue factor and 4 MUM phospholipids. Percentages of the test/control conditions were calculated for the peak height (% peak), endogenous thrombin potential (% ETP) and velocity index (% VI). RESULTS: XACT times were shorter, PMP levels, peak height and velocity index of thrombin generation were higher in SCD patients than controls. Lag time and ETP were not different between the two groups. % peak, % ETP and % VI were higher in patients than controls. Significant correlations were found between PMP levels and XACT, also between PMP levels and peak height, velocity index, ETP and their respective percentages to the control condition, but not with lag time. Double heterozygous patients showed intermediate values for XACT and TG parameters. No significant difference was observed when comparing patients at steady-state versus vaso-occlusive crisis. CONCLUSION: High procoagulant activity of ePL was observed in the platelet-free plasma of SCD children, probably borne by procoagulant microparticles. This may contribute to a high hemostatic potential and predisposition to thrombotic complications in these patients. PMID- 22079447 TI - Socio-demographic characteristics of children experiencing socioeconomic disadvantage who meet physical activity and screen-time recommendations: the READI study. AB - OBJECTIVE: To identify socio-demographic characteristics of children from socioeconomically disadvantaged neighbourhoods who meet physical activity and screen recommendations. METHOD: Children aged 5-12 years (n=373; 45% boys) were recruited in 2007 from socioeconomically disadvantaged urban and rural areas of Victoria, Australia. Children's physical activity, height and weight were objectively measured. Mothers reported their highest level of education, and proxy-reported their child's usual screen-time. Odds ratios (OR) and 95% confidence intervals (95% CI) examined odds of meeting physical activity (>60 minutes/day) and screen (<= 120 minutes/day) recommendations according to socio demographic characteristics. RESULTS: Approximately 84% of children met physical activity and 43% met screen recommendations. Age was inversely associated with odds of meeting physical activity and screen recommendations, and overweight/obese status was associated with lower odds of meeting screen recommendations (boys: OR=0.39, 95%CI=0.16-0.95; girls: OR=0.47, 95%CI=0.26 0.83). Among boys, living in a rural area was positively associated with meeting screen recommendations (OR=3.08, 95%CI=1.42-6.64). Among girls, high levels of maternal education were positively associated with meeting screen recommendations (OR=2.76, 95%CI=1.33-5.75). CONCLUSION: Specific socio-demographic characteristics were associated with odds of meeting physical activity and screen recommendations. Identifying factors associated with such 'resilience' among this group may provide important learnings to inform future physical activity promotion initiatives. PMID- 22079448 TI - Neural insensitivity to upticks in value is associated with the disposition effect. AB - The disposition effect is a phenomenon in which investors hold onto losing assets longer than they hold onto gaining assets. In this study, we used functional magnetic resonance imaging (fMRI) to measure the response of valuation regions in the brain during the decision to keep or to sell an asset that followed a random walk in price. The most common explanation for the disposition effect is preference-based: namely, that people are risk-averse over gains and risk-seeking over losses. This explanation would predict correlations between individuals' risk-preferences, the magnitude of their disposition effect, and activation in valuation structures of the brain. We did not observe these correlations. Nor did we find evidence for a realization utility explanation, which would predict differential responses in valuation regions during the decision to sell versus keep an asset that correlated with the magnitude of the disposition effect. Instead, we found an attenuated ventral striatum response to upticks in value below the purchase price in some individuals with a large disposition effect. Given the role of the striatum in signaling prediction error, the blunted striatal response is consistent with the expectation that an asset will rise when it is below the purchase price, thus spurring loss-holding behavior. This suggests that for some individuals, the disposition effect is likely driven by a belief that the asset will eventually return to the purchase price, also known as mean reversion. PMID- 22079449 TI - Common inhibitory prefrontal activation during inhibition of hand and foot responses. AB - Previous neuroimaging studies using manual Stop signal task showed the inhibitory related areas in the pre-supplementary motor area (pre-SMA) and ventrolateral prefrontal cortex (VLPFC). However, most previous studies employed the manual response inhibition task and the brain representation of the response inhibition of the other body parts has been rarely studied. To further understand the precise brain processing of response inhibition, we performed the event-related fMRI study of Stop signal tasks using the hand and foot response to reveal the common prefrontal region relevant for response inhibition in 13 subjects. We found that the pre-SMA and bilateral VLPFC were commonly activated in successful response inhibition both for hand and foot tasks. The comparison of brain activation between hand and foot response inhibition tasks did not show any significant difference in the prefrontal area. In addition, there was no significant difference for peak coordinates in the pre-SMA and bilateral VLPFC between hand and foot tasks. These findings indicate the common neural network for inhibition of initiated responses regardless of the hand and foot. PMID- 22079450 TI - Phase stability in fMRI time series: effect of noise regression, off-resonance correction and spatial filtering techniques. AB - Although the majority of fMRI studies exploit magnitude changes only, there is an increasing interest regarding the potential additive information conveyed by the phase signal. This integrated part of the complex number furnished by the MR scanners can also be used for exploring direct detection of neuronal activity and for thermography. Few studies have explicitly addressed the issue of the available signal stability in the context of phase time-series, and therefore we explored the spatial pattern of frequency specific phase fluctuations, and evaluated the effect of physiological noise components (heart beat and respiration) on the phase signal. Three categories of retrospective noise reduction techniques were explored and the temporal signal stability was evaluated in terms of a physiologic noise model, for seven fMRI measurement protocols in eight healthy subjects at 3T, for segmented CSF, gray and white matter voxels. We confirmed that for most processing methods, an efficient use of the phase information is hampered by the fact that noise from physiological and instrumental sources contributes significantly more to the phase than to the magnitude instability. Noise regression based on the phase evolution of the central k-space point, RETROICOR, or an orthonormalized combination of these were able to reduce their impact, but without bringing phase stability down to levels expected from the magnitude signal. Similar results were obtained after targeted removal of scan-to-scan variations in the bulk magnetic field by the dynamic off resonance in k-space (DORK) method and by the temporal off-resonance alignment of single-echo time series technique (TOAST). We found that spatial high-pass filtering was necessary, and in vivo a Gaussian filter width of 20mm was sufficient to suppress physiological noise and bring the phase fluctuations to magnitude levels. Stronger filters brought the fluctuations down to levels dictated by thermal noise contributions, and for 62.5mm(3) voxels the phase stability was as low as 5 mrad (0.27 degrees ). In conditions of low SNR(o) and high temporal sampling rate (short TR); we achieved an upper bound for the phase instabilities at 0.0017 ppm, which is close to the dHb contribution to the GM/WM phase contrast. PMID- 22079451 TI - Self-face evaluation and self-esteem in young females: an fMRI study using contrast effect. AB - Self-evaluation is affected by facial attractiveness, particularly in females, and may be related to self-esteem. Self-face evaluation is relative to the attractiveness of others ("contrast effect"). In this functional magnetic resonance imaging (fMRI) study, we examined both the neural correlates of self face evaluation using the contrast effect and a neural relationship between self face evaluation and self-esteem. We prepared the following three types of "target faces": one's own face (S), a close friend's face (F), and an unfamiliar face (O). They were randomly intermingled among same-sex unfamiliar foils during two block-types. Our intention was to evoke positive evaluations of target faces using unattractive foils in one block-type, and negative evaluations using attractive foils in the other. The posterior cingulate cortex (PCC) and ventral tegmental area (VTA) exhibited greater activation from the positive modulation for S than for O. Activation in these regions was positively correlated with self esteem and showed the same tendency between S and F. PCC and VTA, which have been implicated in the processing of self-relatedness and reward, respectively, might play a role in the processing of positive self-face evaluation as self referential stimuli and social rewards, respectively. These results suggested that the PCC and the VTA are the neural correlates of positive self-face evaluation, and that there is a neural relationship between self-face evaluation and self-esteem. The positive evaluation of a close friend's face might be perceived and processed in the same way as one's own face. PMID- 22079452 TI - A short-scan method for k(3) estimation with moderately reversible PET ligands: application of irreversible model to early-phase PET data. AB - Long dynamic scans (60-120 min) are often required for estimating the k(3) value, an index of receptor density, by positron emission tomography (PET). However, the precision of k(3) is usually low in kinetic analyses for reversible PET ligands compared with irreversible ligands. That is largely due to unstable estimation of the dissociation rate constant, k(4). We propose a novel '3P+' method for estimating k(3) of moderately reversible ligands, where a 3-parameter model without k(4) is applied to early-phase PET data to obtain a good model-fit of k(3) estimation. By using [(11)C] Pittsburgh compound B (PIB) (k(4) = 0.018/min) as an example of a moderately reversible ligand, the 3P+ method simulation with a 28 min PET scan yielded less than 3% k(3) relative bias with a +100% k(3) change. In [(11)C]PIB PET scans of 15 normal controls (NC) and nine patients with Alzheimer's disease (AD), the 3P+ method provided a precise k(3) estimate (mean SE of 13.6% in parietal cortex; covariance matrix method). The results revealed linear correlations (r = 0.964) of parietal k(3) values in 24 subjects between 28minute 3P+ method and conventional 90 minute 4-parameter method. A good separation of k(3) between NC and AD groups (P < 0.001; t-test) was replicated in 28 minute 3P+ method. The short-scan 3P+ method may be a practical alternative method for analyzing reversible ligands. PMID- 22079453 TI - Gray matter nulled and vascular space occupancy dependent fMRI response to visual stimulation during hypoxic hypoxia. AB - Two cerebral blood volume (CBV)-weighted fMRI techniques, gray matter nulled (GMN) and vascular space occupancy (VASO)-dependent techniques at spatial resolution of 2 * 2 * 5 mm(3), were compared in the study investigating functional responses in the human visual cortex to stimulation in normoxia (inspired O(2) = 21%) and mild hypoxic hypoxia (inspired O(2) = 12%). GMN and VASO signals and T(2)* were quantified in activated voxels. While the CBV weighted signal changes in voxels activated by visual stimulation were similar in amplitude in both fMRI techniques in both oxygenation conditions, the number of activated voxels during hypoxic hypoxia was significantly reduced by 72 +/- 22% in GMN fMRI and 66 +/- 23% in VASO fMRI. T(2)* prolonged in GMN and VASO activated voxels in normoxia by 1.6 +/- 0.5 ms and 1.7 +/- 0.5 ms, respectively. In hypoxia, however, T(2)* shortened in GMN-activated voxels by 0.7 +/- 0.6 ms (p < 0.001 relative to normoxia), but prolonged in VASO-activated ones by 1.1 +/- 0.6 ms (p < 0.05 relative to normoxia). The data show that the hemodynamic responses to visual stimulation were not affected by hypoxic hypoxia, but T(2)* increases by both CBV-weighted fMRI techniques were smaller in activated voxels in hypoxia. The mechanisms influencing GMN fMRI signal in both oxygenation conditions were explored by simulating effects of the oxygen extraction fraction (OEF) and partial voluming with cerebral spinal fluid (CSF) and white matter in imaging voxels. It is concluded that while GMN fMRI data point to increased, rather than decreased OEF during visual stimulation in hypoxia, partial voluming by CSF is likely to affect the CBV quantification by GMN fMRI under the experimental conditions used. PMID- 22079454 TI - Genome-wide supported risk variant for bipolar disorder alters anatomical connectivity in the human brain. AB - Bipolar disorder is a devastating, highly heritable mental disorder related to disturbed connectivity between limbic and frontal brain areas. A meta-analysis of genome-wide association studies as well as independent replications showed ankyrin 3 (ANK3) to be one of the best-supported risk genes for bipolar disorder. Using an imaging genetics approach employing diffusion tensor imaging in 88 healthy volunteers, we show decreased white matter integrity, indicated by lower fractional anisotropy and longitudinal diffusivity, in healthy carriers of the ANK3 rs10994336 risk genotype in the anterior limb of the internal capsule. We are also able to show that the resulting alterations of cortical-striatal thalamic circuits are related to impaired set-shifting and increased risk-taking. For risk-allele carriers of ANK3 rs9804190 no white matter alterations or neuropsychological impairments were observed. In sum, our findings show that ANK3 rs10994336 or a variant in linkage-disequilibrium is functional in the human brain and also influences behavioral phenotypes related to bipolar disorder. PMID- 22079455 TI - The link between visual exploration and neuronal activity: a multi-modal study combining eye tracking, functional magnetic resonance imaging and transcranial magnetic stimulation. AB - In the present multi-modal study we aimed to investigate the role of visual exploration in relation to the neuronal activity and performance during visuospatial processing. To this end, event related functional magnetic resonance imaging er-fMRI was combined with simultaneous eye tracking recording and transcranial magnetic stimulation (TMS). Two groups of twenty healthy subjects each performed an angle discrimination task with different levels of difficulty during er-fMRI. The number of fixations as a measure of visual exploration effort was chosen to predict blood oxygen level-dependent (BOLD) signal changes using the general linear model (GLM). Without TMS, a positive linear relationship between the visual exploration effort and the BOLD signal was found in a bilateral fronto-parietal cortical network, indicating that these regions reflect the increased number of fixations and the higher brain activity due to higher task demands. Furthermore, the relationship found between the number of fixations and the performance demonstrates the relevance of visual exploration for visuospatial task solving. In the TMS group, offline theta bursts TMS (TBS) was applied over the right posterior parietal cortex (PPC) before the fMRI experiment started. Compared to controls, TBS led to a reduced correlation between visual exploration and BOLD signal change in regions of the fronto-parietal network of the right hemisphere, indicating a disruption of the network. In contrast, an increased correlation was found in regions of the left hemisphere, suggesting an intent to compensate functionality of the disturbed areas. TBS led to fewer fixations and faster response time while keeping accuracy at the same level, indicating that subjects explored more than actually needed. PMID- 22079456 TI - Quadratic component analysis. AB - I present a method for analyzing multichannel recordings in response to repeated stimulus presentation. Quadratic Component Analysis (QCA) extracts responses that are stimulus-induced (triggered by the stimulus but not precisely locked in time), as opposed to stimulus-evoked (time-locked to the stimulus). Induced responses are often found in neural response data from magnetoencephalography (MEG), electroencephalography (EEG), or multichannel electrophysiological and optical recordings. The instantaneous power of a linear combination of channels can be expressed as a weighted sum of instantaneous cross-products between channel waveforms. Based on this fact, a technique known as Denoising Source Separation (DSS) is used to find the most reproducible "quadratic component" (linear combination of cross-products). The linear component with a square most similar to this quadratic component is taken to approximate the most reproducible evoked activity. Projecting out the component and repeating the analysis allows multiple induced components to be extracted by deflation. The method is illustrated with synthetic data, as well as real MEG data. At unfavorable signal to-noise ratios, it can reveal stimulus-induced activity that is invisible to other approaches such as time-frequency analysis. PMID- 22079457 TI - Cloning, identification and functional characterization of a pi-class glutathione S-transferase from the freshwater mussel Cristaria plicata. AB - Glutathione-S-transferases (GSTs) are multifunctional phase II detoxification enzymes that catalyze the attachment of electrophilic substrates to glutathione and play an important role in protecting organisms against the toxicity of reactive oxygen species (ROS). The piGST cDNA was cloned and sequenced after rapid amplification of cDNA ends (RACE) from the freshwater mussel Cristaria plicata. The comparison of the deduced amino acid sequences with GSTs from other species showed that the enzymes belonged to the pi-class and the amino acids defining the binding sites of glutathione (G-site) and for xenobiotic substrates (H-site) were highly conserved. The Cp-piGST cDNA is 816 nucleotides (nt) in length and contained a 615 nt open reading frame (ORF) encoding 205 amino acid residues, and has 19 nt of 5' untranslated region (UTR) and a 3' UTR of 182 nt including a tailing signal (AATAAA) and a poly (A) tail. The molecular weight of the predicted piGST is 23.4 kDa, with the calculated PI being 5.2. The mRNA transcript of Cp-piGST could be detected in all the examined tissues with highest expression level in hepatopancreas. The expression level of Cp-piGST in hepatopancreas and gill showed similar trend that were significantly increased after bacterial challenge compared to the control group at 12 h. Furthermore, the recombinant Cp-piGST with high enzyme activity was induced to be expressed as a soluble form by IPTG at 20 degrees C for 8 h, and then was purified by using the native Ni(2+) affinity chromatography. The specific activity of the purified soluble Cp-piGST enzyme into pET30 was 2.396 MUmol/min/mg, and which into pET32 was 1.706 MUmol/min/mg. The recombinant Cp-piGST had a maximum activity at approximately pH 8.0, and its optimum temperature was 37 degrees C. The recombinant Cp-piGST enzyme activity became lower gradually with the denaturant concentration increasing. PMID- 22079458 TI - Preoperative inpatient hospitalization and risk of perioperative infection following elective vascular procedures. AB - BACKGROUND: Health care-associated infections are not uncommon after elective vascular surgery and can negatively impact mortality rates and hospital resource utilization. Identification of modifiable risk factors for perioperative infection is critical for efforts aimed toward reducing their incidence. We evaluated the associations between preoperative inpatient hospitalization and perioperative surgical site infection (SSI), pneumonia, and urinary tract infection (UTI) following elective vascular surgery procedures. METHODS: Vascular procedures were identified from the 2005 to 2008 American College of Surgeons National Safety Quality Improvement Participant User Data File by using primary Current Procedural Terminology (CPT) codes. Perioperative infections were evaluated as outcomes based on three categories: SSI, pneumonia, and UTI. Patients admitted >=1 day before operation were considered inpatients before surgery. Associations between preoperative inpatient hospitalization and perioperative SSI, pneumonia, and UTI were evaluated using the Cochran-Armitage trend test and multivariable logistic regression. RESULTS: In total 40,669 elective vascular procedures were identified, of which 7,514 (18.5%) were preoperative inpatients. Patients with preoperative inpatient hospitalization had a greater frequency of age >80 years and dependent functional status and also had higher rates of several comorbid conditions, including congestive heart failure, severe chronic obstructive pulmonary disease, >10% weight loss over the past 6 months, history of bleeding disorder, and current smoker within 1 year, than patients admitted on the same day of their procedure. The overall rates of SSI, pneumonia, and UTI were 3.2%, 1.9%, and 1.4%, respectively. Patients with preoperative inpatient hospitalization had higher 30-day incidence of SSI (4.5 vs. 2.9%), pneumonia (3.1 vs. 1.6%), and UTI (2.3 vs. 1.2%). In multivariable models including preoperative risk factors, preoperative inpatient hospitalization was associated with increased 30-day risk of SSI (odds ratio [OR], 1.21; 95% confidence interval [CI]: 1.06-1.39; p = 0.0066), pneumonia (OR, 1.64; 95% CI: 1.39-1.94; p < 0.0001), and UTI (OR, 1.46; 95% CI: 1.20-1.77; p < 0.0001). CONCLUSION: Preoperative inpatient hospitalization is associated with higher rates of perioperative SSI, pneumonia, and UTI in patients undergoing elective vascular surgery procedures. Avoidance of unnecessary preoperative hospitalization has potential to reduce rates of perioperative infection, but additional research is needed to develop evidence-based management strategies when hospitalization before elective procedures is necessary. PMID- 22079459 TI - Alternative management of iliac vein injury during anterior lumbar spine exposure. AB - Vascular injuries are, unfortunately, common complications during anterior approach to lumbar spine, with venous injuries occurring most frequently. The L4 L5 level of exposure is associated most commonly with venous injuries because it requires significant mobilization of the vascular structures. We present two cases of left common iliac vein tears encountered during redo anterior exposure for spine revision. This was in the setting of an anterior lumbar interbody fusion at the L4-L5 level and for the repeat disc arthroplasty at the L5-S1 level. We describe the endovascular technique used to successfully repair venous tear with the deployment of a covered stent across the injury, preventing the ligation of the left common iliac vein. PMID- 22079460 TI - Thromboexclusion of the complete aorta in the treatment of chronic type B aneurysm. AB - We report a case of a 55-year-old woman who was referred to us with a huge chronic postdissection thoracoabdominal aneurysm of a maximal intrathoracic diameter of 13.5 cm and signs of intrathoracic imminent rupture with subparietal pleural hemorrhagic effusion. Computed tomography examination revealed that the left lung had undergone complete atelectasis and carnification owing to compression of the left principal bronchus. There were also signs of left kidney atrophy because of the left renal artery originating from the thrombosed false lumen. Owing to delicate preoperative condition, we decided to perform thromboexclusion of the complete aorta with reattachment of all the supra-aortic and visceral branches and complete bipolar exclusion of thoracoabdominal aorta. The patient was discharged from the hospital on the 35th postoperative day in a good condition. Following computed tomography scan revealed complete thrombosis of the excluded portion of the aorta. PMID- 22079461 TI - Socioeconomic position, comorbidity, and mortality in aortic aneurysms: a 13-year prospective cohort study. AB - BACKGROUND: To evaluate factors associated with incidence and 3-year all-cause mortality in patients with aortic aneurysm (AA). The design is sex and age stratified (60-79 and 80-90 years) prospective cohort. By using the population register, we constituted a cohort of all men and women born between 1900 and 1930 and living in Scania by 1991, and followed them for 13 years. Identification of AA was based on hospital discharge diagnosis obtained from the Swedish Patient Register or from the information on death certificates from the Cause of Death Register. METHODS: We applied stepwise Cox regression and investigated both AA incidence (1991-2003) as well as 3-year survival after the first hospitalization for AA. RESULTS: We found an inverse relation between AA incidence and previous hospitalization by diabetes mellitus in women (hazard ratio [HR]: 0.41; 95% confidence interval [CI]: 0.19-0.88) and in men (HR: 0.38; 95% CI: 0.24-0.61) aged 60-79 years. Three-year all-cause mortality after diagnosis of AA was 58.6% in women, 50.2% in men, 72.9% in octogenarians, and 43.7% for nonoctogenarians. Low income, chronic respiratory diseases, cerebrovascular diseases, dementia, systemic connective tissue disorders, renal failure, and malignant neoplasms were independent factors for mortality in 60-79-year-old men with AA. CONCLUSIONS: Inferior socioeconomic position is associated with increased 3-year all-cause mortality in 60-79-year-old men with AA. PMID- 22079462 TI - Mesocavoatrial shunt for Budd-Chiari syndrome: a case report with long-term follow-up. AB - BACKGROUND: A case of mesocavoatrial shunting for the treatment of Budd-Chiari syndrome (BCS) with long-term follow-up is reported. METHODS: A 25-year-old man with stage II BCS was treated with a mesocavoatrial shunt to decompress the portal and IVC hypertension. During the 6-year follow-up, the patient was able to resume work as a salesperson and has since led a normal life. His graft remains patent. CONCLUSION: A mesocavoatrial shunt can simultaneously decompress portal and IVC hypertension and has satisfactory long-term patency. A mesocavoatrial shunt can be used to treat patients with severe BCS who could not be successfully treated with medical therapy and intervention. PMID- 22079463 TI - Symptomatic aneurysm of a perforating peroneal artery after a blunt trauma. AB - A 48-year-old woman was referred to us for a pulsatile and painful mass on the right leg after a trauma occurred 2 months earlier. The duplex scan revealed the presence of an aneurysm of the perforating peroneal artery. The patient underwent an endovascular coil embolization of the aneurysm. The duplex-scan follow-up showed the patency of the peroneal vessel and the complete aneurysm thrombosis. The patient was discharged in good condition without pain. In literature, only four cases of aneurysm of perforating peroneal artery aneurysm, all with a clear traumatic etiology, are reported. In this case, the endovascular treatment was safe and effective. PMID- 22079464 TI - Case report of a patient with iliac occlusive disease due to pseudoxantoma elasticum and review of the bibliography. AB - BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by progressive calcification and fragmentation of elastic fibers in the skin, the retina, and the cardiovascular system, and is also termed as elastorrhexia. The purpose of this case presentation is to report the case of a PXE patient with an atypical localization of atherosclerotic lesion (iliac arteries) and that this rare disease should always be included in the differential diagnosis of patients with premature atheromatosis. METHODS AND RESULTS: A 58-year-old patient, suffering from PXE, came to our clinic to seek advice for his severe lower limb claudication. The image of the magnetic resonance angiography of his aorta, iliac arteries, and lower limb arteries demonstrated total occlusion of the left common iliac artery and preocclusive stenosis of the orifice on the right common iliac artery. The patient was treated successfully by angioplasty with kissing stent placement at the iliac arteries, and 6 months later, he is symptom-free, with ankle-brachial indexes of 1.0 and 1.05 on the left and right legs, respectively. CONCLUSION: This case report presentation has a primary goal to show that the disease may cause atypical localizations of atherosclerosis (iliac arteries) and a secondary goal to demonstrate that endovascular treatment in these patients may be a safe and viable option. It is also a good opportunity for a brief review of the bibliography. PMID- 22079465 TI - Using indocyanine green fluorescent lymphography and lymphatic-venous anastomosis for cancer-related lymphedema. AB - Advances in cancer therapy have increased the importance of improvement of quality of life after cancer survival. Cancer-related lymphedema or secondary lymphedema that occurs after lymph node dissection in resection of tumors of abdominal visceral organs can impair quality of life. However, standard curative treatment for secondary lymphedema has not been established. This may be due to the lack of a method for early diagnosis of lymphedema, and because of selection of conservative treatment such as compression therapy to delay edema progression in many cases. To develop a curative approach, we have performed definite diagnosis of early-stage lymphedema using magnetic resonance imaging and an indocyanine green fluorescent lymphography, followed by surgical treatment with lymphatic-venous anastomosis using supermicrosurgery. Herein, we report the first case of secondary lymphedema in which we performed early diagnosis and surgery using these techniques and achieved an almost complete cure of lymphedema. We suggest that early diagnostic imaging and early microsurgery is the key of lymphedema treatment. PMID- 22079466 TI - CD133+ liver cancer stem cells modulate radioresistance in human hepatocellular carcinoma. AB - CD133 is a cancer stem-cell (CSC) marker associated with radioresistance and chemoresistance in various cancers. In the present study, CD133-expressing liver cancer cells following radiation exposure showed higher activation of MAPK/PI3K signaling pathway and reduction in reactive oxygen species levels compared to CD133- cells. The in vivo study with a xenograft model showed increased tumor formation in irradiated CD133+ cell-injected nude mice compared to the CD133- group, suggesting that CD133 contributes to radioresistance in HCC. Therefore, CD133-expressing liver cancer cells have anti-apoptotic and radioresistance properties that may be useful to improve anti-cancer treatments, including chemotherapy/radiotherapy of HCC. PMID- 22079467 TI - Differential function of lysophosphatidic acid receptors in cell proliferation and migration of neuroblastoma cells. AB - Lysophosphatidic acid (LPA) is a bioactive lipid mediator that induces diverse cellular biological effects and interacts with G protein-coupled transmembrane LPA receptors. In the present study, to assess biological roles of LPA receptors in the pathogenesis of tumor cells, each LPA receptor (Lpar1, Lpar2 or Lpar3) expressing rat neuroblastoma B103 cells (lpa1-1, lpa2-2 or lpa3-3-2 cells, respectively) were used. In cell motility and invasion assay, lpa2-2 and lpa3-3-2 cells showed significant higher intrinsic activity without LPA treatment than LPA receptor-unexpressing AB2-1bf cells. LPA treatment further increased cell motility of these cells, which was suppressed by the pretreatment with inhibitors of Gi, Gq protein, or ROCK. By contrast, lpa1-1 cells markedly decreased intrinsic cell motility and invasion, compared with AB2-1bf cells. Constitutively active mutant Lpar1-expressing cells (lpa1Delta-1) showed significant high motility, comparable with those of lpa2-2 and lpa3-3-2. In soft agar assay, lpa3 3-2 and lpa1Delta-1 cells showed colony formation, but other cells failed. These results suggest that LPA receptors may play different roles in cell proliferation and migration of rat neuroblastoma cells. PMID- 22079468 TI - Significance of increased blastic-appearing cells in bone marrow following myeloablative unrelated cord blood transplantation in adult patients. AB - An abnormal increase of nonleukemic blastic-appearing lymphocytes in bone marrow (BM) specimens has been reported after unrelated cord blood transplantation (UCBT). This study analyzed the incidence, chronology, biological features, and clinical significance of elevated numbers of these cells in a series of 165 consecutive adult patients demonstrating myeloid engraftment after myeloablative UCBT in a single institution. The patients' BM samples were routinely evaluated by cytomorphology at different time points after UCBT. When >=5% of blastic appearing cells were detected by cytomorphology in the BM, samples were also evaluated by multiparametric flow cytometry to characterize these cells. Systematic chimerism analyses of BM samples using PCR amplification of short tandem repeat markers were performed. Forty-three patients (cumulative incidence, 26.1%) demonstrated >=5% of nonmalignant blastic-appearing cells in BM after a median of 101 days after UCBT (range, 28-377 days). All of these patients had full-donor chimerism and a clinical course without leukemic relapse. Multiparametric flow cytometry analyses performed in 36 of the 43 patients showed a polyclonal expansion of B lymphocytes with a broad spectrum of maturation stages. An increased number of nonmalignant blastic-appearing cells was significantly associated with a high number of lymphocytes infused at the time of UCBT and with low rates of acute and chronic extensive graft-versus-host disease, suggesting a potential immunoregulatory role of these cells. The observation of >=5% nonmalignant blastic-appearing cells in BM samples after myeloablative UCBT is frequent, and these should be distinguished from malignant blasts. PMID- 22079469 TI - Evaluation of oral beclomethasone dipropionate for prevention of acute graft versus-host disease. AB - Results from two randomized trials have shown that oral beclomethasone dipropionate (BDP) is effective for treatment of acute gastrointestinal graft versus-host disease. Here, we report results of a double-blind, randomized placebo-controlled phase II study designed to test the hypothesis that acute graft-versus-host disease could be prevented by administration of oral BDP, beginning before hematopoietic cell transplantation and continuing until day 75 after hematopoietic cell transplantation after myeloablative conditioning. Study drug (BDP or placebo) was administered as 1-mg immediate-release formulation plus 1-mg delayed-release formulation orally four times daily. According to the primary endpoint, systemic glucocorticoid treatment for graft-versus-host disease was given to 60 of the 92 participants (65%) in the BDP arm, versus 31 of 46 participants (67%) in the placebo arm. The secondary efficacy endpoints showed no statistically significant differences between the two arms. The proportion of participants who took at least 90% of the prescribed study drug during the first 4 weeks after hematopoietic cell transplantation was 54% overall. Lower severity of mucositis strongly correlated with higher adherence to the schedule of study drug administration. Inconsistent adherence related to mucositis during recovery after myeloablative conditioning may have obscured a beneficial therapeutic effect in the current study. PMID- 22079470 TI - Phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for allogeneic hematopoietic cell transplantation. AB - We conducted a phase I-II study of transplantation conditioning with clofarabine melphalan-alemtuzumab for patients with advanced hematologic malignancies. Ten patients were accrued to the phase I portion, which utilized an accelerated titration design. No dose-limiting toxicity was observed, and clofarabine 40 mg/m(2) * 5, melphalan 140 mg/m(2) * 1, and alemtuzumab 20 mg * 5 was adopted for the phase II study, which accrued 72 patients. Median age was 54 years. There were 44 patients with acute myelogenous leukemia or myelodysplastic syndromes, 27 with non-Hodgkin lymphoma, and nine patients with other hematologic malignancies. The largest subgroup of 35 patients had American Society for Blood and Marrow Transplantation high-risk, active disease. All evaluable patients engrafted with a median time to neutrophil and platelet recovery of 10 and 18 days, respectively. The cumulative incidence of treatment-related mortality was 26% at 1 year. Cumulative incidence of relapse was 29% at 1 year. Overall survival was 80% (95% confidence interval [CI], 71-89) at 100 days and 59% (95% CI, 47-71) at 1 year. Progression-free-survival was 45% (95% CI, 33-67) at 1 year. Rapid-onset renal failure was the main toxicity in the phase II study and more frequent in older patients and those with baseline decrease in glomerular filtration rate. Grade 3-5 renal toxicity was observed in 16 of 74 patients (21%) treated at the phase II doses. Clofarabine-melphalan-alemtuzumab conditioning yields promising response and duration of response, but renal toxicity poses a considerable risk particularly in older patients. PMID- 22079472 TI - Transplantation for lymphoma: good for the brain as well as the body? PMID- 22079471 TI - A Phase I study of gemtuzumab ozogamicin (GO) in combination with busulfan and cyclophosphamide (Bu/Cy) and allogeneic stem cell transplantation in children with poor-risk CD33+ AML: a new targeted immunochemotherapy myeloablative conditioning (MAC) regimen. AB - Children with high-risk acute myelogenous leukemia (AML) (induction failure [IF], refractory relapse [RR], third complete remission [CR3]) have dismal outcomes. Over 80% of AML patients express CD33, a target of gemtuzumab ozogamicin (GO). GO is an active drug in childhood AML but has not been studied in a myeloablative conditioning regimen. We sought to determine the safety of GO in combination with busulfan/cyclophosphamide (Bu/Cy) conditioning before allogeneic hematopoietic stem cell transplantation (alloSCT). GO was administered on day -14 at doses of 3.0, 4.5, 6.0, and 7.5 mg/m(2), busulfan on days -7, -6, -5, -4 (12.8-16.0 mg/kg), and cyclophosphamide on days -3 and -2 (60 mg/kg/day). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. We enrolled 12 patients: 8 IF, 3 RR, 1 CR3; median age: 3 years (1-17); median follow-up: 1379 days (939-2305). Nine received umbilical cord blood (UCB), 2 matched unrelated donors (MUDs) and 1 HLA-matched sibling donor: 3 patients each at GO doses of 3.0, 4.5, 6.0, or 7.5 mg/m(2). No dose-limiting toxicities secondary to GO were observed. Day 100 treatment-related mortality (TRM) was 0%. Myeloid and platelet engraftment was observed in 92% and 75% of patients at median day 22 (12-40) and 42 (21-164), respectively. Median day +30 donor chimerism was 99% (85%-100%). The probability of grade II-IV acute graft-versus-host disease (aGVHD) was 42% and chronic GVHD (cGVHD) was 28%. One-year overall survival (OS) and event-free survival (EFS) was 50% (95% confidence interval [CI], 20.8-73.6). GO combined with Bu/Cy regimen followed by alloSCT is well tolerated in children with poor-risk AML. GO at 7.5 mg/m(2) in combination with Bu/Cy is currently being tested in a phase II study. PMID- 22079473 TI - Disinfection of gram-negative and gram-positive bacteria using DynaJets(r) hydrodynamic cavitating jets. AB - Cavitating jet technologies (DynaJets(r)) were investigated as a means of disinfection of gram-negative Escherichia coli, Klebsiellapneumoniae, Pseudomonas syringae, and Pseudomonas aeruginosa, and gram-positive Bacillus subtilis. The hydrodynamic cavitating jets were found to be very effective in reducing the concentrations of all of these species. In general, the observed rates of disinfection of gram-negative species were higher than for gram-positive species. However, different gram-negative species also showed significant differences (P. syringae 6-log(10) reduction, P. aeruginosa 2-log(10) reduction) under the same conditions. Disinfection of E. coli repeatedly showed five orders of magnitude reduction in concentration within 45-60-min at low nozzle pressure (2.1 bar). Optimization of nozzle design and operating pressures increased disinfection rates per input energy by several orders of magnitude. The power efficiencies of the hydrodynamic cavitating jets were found to be 10-100 times greater than comparable ultrasonic systems. PMID- 22079474 TI - Protein contact map prediction using multi-stage hybrid intelligence inference systems. AB - Proteins are one of the most important molecules in organisms. Protein function can be inferred from its 3D structure. The gap between the number of discovered protein sequences and the number of structures determined by the experimental methods is increasing. Accurate prediction of protein contact map is an important step toward the reconstruction of the protein's 3D structure. In spite of continuous progress in developing contact map predictors, highly accurate prediction is still unresolved problem. In this paper, we introduce a new predictor, JUSTcon, which consists of multiple parallel stages that are based on adaptive neuro-fuzzy inference System (ANFIS) and K nearest neighbors (KNNs) classifier. A smart filtering operation is performed on the final outputs to ensure normal connectivity behaviors of amino acids pairs. The window size of the filter is selected by a simple expert system. The dataset was divided into testing dataset of 50 proteins and training dataset of 450 proteins. The system produced an average accuracy of 45.2% for the sequence separation of six amino acids. In addition, JUSTcon outperformed SVMcon and PROFcon predictors in the cases of large separation distances. JUSTcon produced an average accuracy of 15% for the sequence separation of 24 amino acids after applying it on CASP9 targets. PMID- 22079475 TI - Antimetastatic potential of cardiotoxin III involves inactivation of PI3K/Akt and p38 MAPK signaling pathways in human breast cancer MDA-MB-231 cells. AB - AIM: The aim of this study is to determine whether cardiotoxin III (CTX III) inhibited the metastasis in MDA-MB-231 cells and to further explain its possible mechanisms. MAIN METHODS: The MTT assay, wound healing assay, Boyden chamber invasion assay, zymography analysis, reverse transcriptase polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), inhibitor assay, and Western blot analysis were used to reveal molecular events of CTX III in this study. KEY FINDINGS: During treatment with non-toxic doses of CTX III, not only cell migration and invasion were markedly suppressed but the expression/activity of matrix metalloproteinase-9 (MMP-9) was also significantly and selectively suppressed in a concentration-dependent manner. In addition, CTX III decreased the nuclear protein level of nuclear factor kappa B (NF-kappaB), and pretreatment with NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) also reduced MMP-9 expression/activity and cell migration. Our biochemical assays indicated that CTX III potently suppressed the phosphorylation of p38 mitogen-activated protein kinase (MAPK), phosphatidylinositide-3-kinase (PI3K) and Akt. Additionally, the treatment of inhibitors specific for p38 MAPK (SB203580) or PI3K (wortmannin) to cells could result in a reduced expression of NF-kappaB and MMP-9 expression, concomitantly with an inhibition on cell metastasis. SIGNIFICANCE: These results demonstrated that CTX III inhibition of MDA-MB-231 cells may occur through inactivation of both PI3K/Akt and p38 MAPK signaling pathways, exerting inhibitory effects on NF-kappaB transcriptional factor, thereby decreasing the activity of MMP-9 and then posing an anti-metastatic effect in the cells. PMID- 22079476 TI - Applying radio-frequency identification (RFID) technology in transfusion medicine. AB - ISO/IEC 18000-3 mode 1 standard 13.56 MHz RFID tags have been accepted by the International Society for Blood Transfusion (ISBT) and the United States Food and Drug Administration (FDA) as data carriers to integrate with and augment ISBT 128 barcode data carried on blood products. The use of 13.56 MHz RFID carrying ISBT 128 data structures allows the global deployment and use of RFID, supporting both international transfer of blood and international disaster relief. The deployment in process at the BloodCenter of Wisconsin and testing at the University of Iowa Health Center is the first FDA-permitted implementation of RFID throughout in all phases of blood banking, donation through transfusion. RFID technology and equipment selection will be discussed along with FDA-required RF safety testing; integration with the blood enterprise computing system and required RFID tag performance. Tag design and survivability is an issue due to blood bag centrifugation and irradiation. Deployment issues will be discussed. Use of RFID results in significant return on investment over the use of barcodes in the blood center operations through labor savings and error reduction. PMID- 22079477 TI - Cyclic nucleotide phosphodiesterases: critical modulators of endocrine, metabolic, and cardiovascular function and appealing therapeutic targets. PMID- 22079478 TI - Experimental SSM-CVB3 infection in macaques. AB - OBJECTIVE: To evaluate the pathogenicity of SSM-CVB3 in a macaque model. METHODS: The clinical symptoms of macaques were recorded; hematological, biochemical and histopathological evaluations were completed; viral titers and neutralization titers (NT-titers) in sera were tested; and the mRNA levels of SSM-CVB3, coxsackievirus and adenovirus receptor (CAR) and decay accelerating factor (DAF) were determined. RESULTS: After SSM-CVB3 infection, the macaques showed a lack of activity, a poor appetite, a higher body temperature, and severe diarrhea. The macaques also developed hematuria and albuminuria at 4 to 10 days post inoculation. Virus titers (5.1-6.5 LogTCID(50)/mL) were higher at 6 to 10 days post-inoculation, and NT-titers (6.5-7.3 Log2) reached plateaus at 8 to 14 days post-inoculation. The infected macaques developed serious anemia with decreased RBC and WBC, but the percentages of LYM were increased. The levels of CK, CK-MB, AST and ALT in the sera were 84-169 U/L, 87.6-271.1 U/L, 43-87 U/L and 43-82 U/L, respectively, and all of those were higher than normal. Histological analysis showed obvious cardiac, hepatic and renal damages in the infected macaques and the mRNA contents of SSM-CVB3, CAR and DAF in the heart, liver and kidneys of infected macaques were higher (P<0.05). CONCLUSION: This was the first report on experimental SSM-CVB3 infections in macaques with serious hepatic and renal damage, except for myocarditis. The information obtained from this study suggests that the SSM-CVB3 strain and this macaque model could be used for studying CVB3 induced cardiac, hepatic or renal diseases. PMID- 22079480 TI - The image of nursing as perceived by nurses. AB - PURPOSE: To explore the image of nursing as perceived by nurses. BACKGROUND: Nurses' image has always been a concern among those in the profession. The decision to enter nursing, to remain in nursing, to promote nursing, and to further a career in nursing may be the result of nurses' perception of the image of the profession. No recent studies have been done on how nurses perceive the profession METHODS: A purposeful sample of 13 participants ranging in experience from senior student nurses to Registered Nurses with over 21 years of experience in direct patient care, participated in in-depth interviews. For this descriptive exploratory design, qualitative data were collected and analyzed. FINDINGS: Three broad categories that were significant in how nurses perceive the profession emerged: a) role of nurses, b) nursing knowledge, and c) attitude of nurses. Those about to enter the profession have a positive image of nursing based on their roles and their nursing knowledge. Attitude of nurses significantly influenced participants' perceptions of nursing's professional image. As they progress through their career, nurses have negative perceptions of the profession, influenced by working environment and interactions with others in the health care arena. CONCLUSION: Overall, nurses working in hospitals have negative perceptions of the profession; nurses working in maternal-child health have positive perceptions; nurses' perceptions of nurses working in areas different from theirs are negative; nurses perceive senior nurses in a negative light and senior nurses have negative perceptions of new nurses. PMID- 22079479 TI - Autophagy in the brains of young patients with poorly controlled T1DM and fatal diabetic ketoacidosis. AB - Semi-quantitative neuroradiologic studies, quantitative neuron density studies and immunocytochemistry markers of oxidative stress and neuroinflammation indicate neuronal injury and deficits in young patients with chronic poorly controlled type 1 diabetes mellitus (T1DM). Present data suggest that pathogenesis of the neuronal deficits in young patients, who die as the result of diabetic ketoacidosis (DKA) and brain edema (BE), does not involve apoptosis, a prominent form of regulated cell death in many disease states. To further address this we studied mediators of macroautophagy, endoplasmic reticulum (ER) stress and apoptosis. In all areas studied we demonstrated increased levels of macroautophagy-associated proteins including light chain-3 (LC3) and autophagy related protein-4 (Atg4), as well as increased levels of the ER-associated glucose-regulated protein78/binding immunoglobulin protein (GRP78/BiP) in T1DM. In contrast, cleaved caspase-3 was rarely detected in any T1DM brain regions. These results suggest that chronic metabolic instability and oxidative stress may cause alterations in the autophagy-lysosomal pathway but not apoptosis, and macroautophagy-associated molecules may serve as useful candidates for further study in the pathogenesis of early neuronal deficits in T1DM. PMID- 22079481 TI - Essaying the essay: nursing scholarship and the hegemony of the laboratory. AB - It might appear odd or even perverse to be arguing for the essay as a vehicle for academic thought and writing, particularly given the current emphasis on scientific research and evidence-based practice. In fact, the scholarly essay has virtually ceased to exist as an academic form in practice disciplines such as nursing, excluded by what we will identify and refer to as the hegemony of the laboratory. In a practical as well as an intellectual attempt to reinstate it, this paper is structured in the form of two consecutive short essays. In the first, we identify the character, features and purpose of the scholarly essay and examine its demise as an academic form. In the second, we explore some possible reasons why the essay never became fully accepted as an academic form in nursing. We suggest that the essay is thematically eclectic and stylistically promiscuous, drawing from a broad range of cultural, disciplinary and academic reference points. As such, it presents a challenge to the dominant technical rational approach to academic nursing in both its form and its content, particularly in its disregard for the rigidly imposed genres and structures increasingly demanded by academic nursing journals. PMID- 22079482 TI - Optimization of preparative chromatographic separation of multiple rare earth elements. AB - This work presents a method to optimize multi-product chromatographic systems with multiple objective functions. The system studied is a neodymium, samarium, europium, gadolinium mixture separated in an ion exchange chromatography step. A homogeneous Langmuir Mobile Phase Modified model is calibrated to fit the experiments, and then used to perform the optimization task. For the optimization a multi-objective Differential Evolution algorithm was used, with weighting based on relative value of the components to find optimal operation points along the Pareto front. The objectives of the Pareto front are weighted productivity and weighted yield with purity as an equality constraint. A prioritizing scheme based on relative values is applied for determining the pooling order. A simple rule of thumb for pooling strategy selection is presented. The multi-objective optimization gives a Pareto front which shows the rule of thumb, as a gap in one of the objective functions. PMID- 22079483 TI - Chromatographic and spectroscopic data fusion analysis for interpretation of photodegradation processes. AB - Photodegradation processes are of high relevance in environmental and pharmaceutical contexts, since the fate and identity of photoproducts are often linked to contamination or toxicology issues. The aim of this work is proposing a new general methodology to monitor and interpret photodegradation processes based on chromatographic and spectroscopic measurements and data fusion analysis. The new approach relies on two steps: (a) data fusion of HPLC-DAD-MS runs coming from process monitoring and analysis by soft-modeling multivariate curve resolution (MCR) to achieve the identification of photoproducts and a first insight on their kinetic behavior; and (b) data fusion of UV-vis spectroscopic monitoring data with HPLC-DAD process runs and analysis by hybrid hard- and soft-modeling MCR (HS MCR) to complete the description of the kinetic mechanism of the process and to provide the related rate constants. These data fusions overcome limitations of previous approaches and have never been reported in real examples of process analysis. The ketoprofen photodegradation has been selected as the real case study to illustrate the possibilities of the described approach. In this particular case, a comprehensive description of the kinetics linked to the photochemical degradation of the ketoprofen, with all successive steps, related rate constants and photoproducts formed has been proposed. Four photodegradation products (3-(1-hydroperoxyethyl)benzophenone, 3-acetylbenzophenone, 3-(1 hydroxyethyl)benzophenone and 3-ethvlbenzophenone) could be resolved as a result of the decarboxylation of ketoprofen under UV light and the photodegradation process could be described with a kinetic model including parallel and consecutive reactions. PMID- 22079484 TI - Silicon speciation by gas chromatography coupled to mass spectrometry in gasolines. AB - A method for the speciation of silicon compounds in petroleum products was developed using gas chromatography coupled to mass spectrometry (GC-MS). Prior to analysis, several precautions about storage and conservation were applied for all samples. In spiked gasoline samples, limits of detection between 24 and 69 MUg kg(-1) for cyclic siloxanes (D(4)-D(6)) and between 1 and 7 MUg kg(-1) for other species were obtained. In this study, cyclic siloxanes (D(n)) and one ethoxysilane were quantified for the first time in petroleum products by a specific method based on response factor calculation to an internal standard. This method was applied to four samples of naphthas and gasolines obtained from a steam cracking process. Cyclic siloxanes were predominant in four investigated samples with concentrations ranging between 101 and 2204 MUg kg(-1). Cyclic siloxane content decreased with an increase in their degree of polymerization. During a steam cracking process, silicon concentrations determined by GC-MS SIM (single ion monitoring) significantly increase. This trend was confirmed by ICP OES (inductively coupled plasma optical emission spectroscopy) measurements but a difference on the total silicon content was observed, certainly highlighting the presence of unknown silicon species. GC-MS SIM method gives access to the chemical nature of the silicon species, which is crucial for the understanding of hydrotreatment catalyst poisoning in the oil and gas industry. PMID- 22079485 TI - Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver. AB - Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images. PMID- 22079486 TI - Variant obturator artery complicating uterine artery embolization. PMID- 22079487 TI - Three-dimensional hydrogel structures as optical sensor arrays, for the detection of specific DNA sequences. AB - The fabrication and characterization of surface-attached PEG-diacrylate hydrogel structures and their application as sensing platforms for the detection of specific target sequences are reported. Hydrogel structures were formed by a photopolymerization process, using substrate-bound Eosin Y molecules for the production of free radicals. We have demonstrated that this fabrication process allows for control over hydrogel growth down to the micrometer scale. Confocal imaging revealed relatively large pore structures for 25% (v/v) PEG-diacrylate hydrogels, which appear to lie in tightly packed layers. Our data suggest that these pore structures decrease in size for hydrogels with increasing levels of PEG-diacrylate. Surface coverage values calculated for hydrogels immobilized with 21-mer DNA probe sequences were significantly higher compared to those previously reported for 2- and 3-dimensional sensing platforms, on the order of 10(16)molecules cm(-2). Used as sensing platforms in DNA hybridization assays, a detection limit of 3.9 nM was achieved for hybridization reactions between 21-mer probe and target sequences. The ability of these hydrogel sensing platforms to discriminate between wild-type and mutant allele sequences was also demonstrated, down to target concentrations of 1-2 nM. A reduction in the hybridization time down to a period of 15 min was also achieved, while still maintaining confident results, demonstrating the potential for future integration of these sensing platforms within Lab-on-Chip or diagnostic devices. PMID- 22079488 TI - Is health-related quality of life an independent prognostic factor for 12-month mortality and nursing home placement among elderly patients hospitalized via the emergency department? AB - OBJECTIVES: To assess whether health-related quality of life is an independent prognostic factor for mortality or nursing home placement in frail elderly patients. DESIGN: A prospective, multicenter study with a 12-month follow-up. SETTING: Nine French hospitals. PARTICIPANTS: A total of 1306 patients aged 75 and older hospitalized through an emergency department. MEASUREMENTS: Data obtained from sociodemographic characteristics, Comprehensive Geriatric Assessment and the Duke Health Profile (DHP) were used into a Cox model to identify prognostic variables for 12-month mortality and institutionalization. RESULTS: Crude mortality and nursing home placement rates were 34.1% (n = 445) and 16.1% (n = 210), respectively. Independent prognostic factors identified for mortality were: Comorbidity level (moderate: hazard ratio [HR] [95% confidence interval (CI)] = 1.40 [1.09-1.78]; severe: 2.70 [1.63-4.46]), dependence for activities of daily living (1.68 [1.06-2.67]), pressure sore risk (1.49 [1.16 1.90]), risk of malnutrition (2.09 [1.46-3.00]), delirium (2.25 [1.75-2.90]), and 10-point increase in the DHP perceived health score (0.96 [0.93-0.99]). Independent prognostic factors identified for nursing home placement were the following: living alone at home (1.82 [1.30-2.55]), having 2 children or more (0.71 [0.51-0.99]), dependence for activities of daily living (2.48 [1.39-4.44]), dementia (1.93 [1.39-2.69]), unplanned hospital readmission during follow-up (2.05 [1.45-2.91]), and 10-point increase in the DHP social health score (0.90 [0.83-0.99]). Balance troubles and risk of malnutrition were no more significant when adjusted for the DHP scores and other clinical variables. CONCLUSION: The perceived health and social health scores of the DHP were independent prognostic factors of survival and nursing home placement among hospitalized elderly patients, respectively. When associated with Comprehensive Geriatric Assessment, they could help screen frail patients to set up as early as possible targeted interventions to restore/maintain modifiable prognostic factors, such as nutritional status, functional ability, and social support. PMID- 22079489 TI - Changes in the cannabinoid (CB1) receptor expression level and G-protein activation in kainic acid induced seizures. AB - It has been known for centuries that exogenous cannabinoids, such as tetrahydrocannabinol have anticonvulsant activity. Recent studies have advanced our understanding of the endogenous cannabinoid system and renewed the interest in cannabinoids as a potential treatment for epilepsy. The endogenous cannabinoid system is rapidly activated after seizure activity but still little is known about the molecular mechanisms underlying the role of the cannabinoid system in epilepsy. In this study epileptiform activity was induced by kainic acid (KA) and effects of the CB1 receptor agonists N-(2-Chloroethyl)-5Z,8Z,11Z,14Z eicosatetraenamide (ACEA) on G-protein signaling using the agonist-stimulated [(35)S]GTPgammaS binding assay were evaluated. Control and KA treated rat hippocampus and cortex membranes were used. Our results showed that the ACEA displayed a high potency and efficacy in stimulating the G-proteins and when compared to the control animals, significant enhancements were observed in tissues from the KA treated animals. Potency and efficacy values were in particular increased in the hippocampus tissues. Furthermore, gene expression levels of the cannabinoid receptor 1 (CB1) receptor and cannabinoid receptor interacting protein 1 (CRIP1) were measured by RT-PCR, where both CB1 and CRIP1 expressions were found to be elevated in the KA treated animals. PMID- 22079490 TI - Are estimates of the value of a statistical life exaggerated? AB - The magnitude of the value of a statistical life (VSL) is critical to the evaluation of many health and safety initiatives. To date, the large and rigorous VSL research literature has not explicitly accommodated publication selectivity bias (i.e., the reduced probability that insignificant or negative VSL values are reported). This study demonstrates that doing so is essential. For studies that employ hedonic wage equations to estimate VSL, correction for selection bias reduces the average value of a statistical life by 70-80%. Our meta-regression analysis also identifies several sources for the wide heterogeneity found among reported VSL estimates. PMID- 22079491 TI - Regional specific alterations in brain acetylcholinesterase activity after repeated blast exposures in mice. AB - Acetylcholinesterase (AChE) which catalyzes the hydrolysis of the neurotransmitter acetylcholine has been recognized as one of the major regulators of stress responses after traumatic brain injury (TBI). Repeated blast exposure induces TBI (blast TBI) with a variable neuropathology at different brain regions. Since AChE inhibitors are being used as a line of treatment for TBI, we sought to determine the time course of AChE activity in the blood and different brain regions after repeated blast exposures using modified Ellman assay. Our data showed that repeated blast exposures significantly reduced AChE activity in the whole-blood and erythrocytes by 3-6h, while plasma AChE activity was significantly increased by 3h post-blast. In the brain, significant increase in AChE activity was observed at 6h in the frontal cortex, while hind cortex and hippocampus showed a significant decrease at 6h post-blast, which returned to normal levels by 7 days. AChE activity in the cerebellum and mid brain showed a decrease at 6h, followed by significant increase at 3 days and that was decreased significantly at 14 days post-blast. Medulla region showed decreased AChE activity at 24h post-blast, which was significantly increased at 14 days. These results suggest that there are brain regional and time-related changes in AChE activity after tightly coupled repeated blast exposures in mice. In summary, acute and chronic regional specific changes in the AChE activity after repeated blast exposures warrant systematic evaluation of the possibility of AChE inhibitor therapeutics against blast TBI. PMID- 22079492 TI - Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity. AB - BACKGROUND: IL-4, IL-5, and IL-13 are thought to be central to the allergic asthmatic response. Previous work supposed that the essential source of these cytokines was CD4(+) T(H)2 cells. However, more recent studies have suggested that other innate production of type 2 cytokines might be as important. OBJECTIVES: Nuocytes are a novel population of IL-13-producing innate cells, which are critical for protective immunity in Nippostrongylus brasiliensis infection. Given this, we investigated the potential existence and functional importance of nuocytes in experimental allergic asthma. METHODS: We generated Il4(+/eGFP)Il13(+/Tomato) dual-reporter mice to study cytokine-producing cells during allergic inflammation. We adoptively transferred innate IL-13-producing cells to investigate their role in airways hyperreactivity (AHR). RESULTS: We show that allergen-induced nuocytes infiltrate the lung and are a major innate source of IL-13. CD4(+) T cells in the lung almost exclusively express only IL 13, whereas IL-4-producing T cells were restricted to the draining lymph nodes. Intranasal administration of IL-25 or IL-33 induced IL-13-producing nuocytes in the BAL fluid. Strikingly, adoptive transfer of wild-type nuocytes, but not Il13( /-) nuocytes, into Il13(-/-) mice, which are normally resistant to IL-25-induced AHR, restored airways resistance and lung cell infiltration. CONCLUSIONS: These findings identify nuocytes as a novel cell type in allergic lung inflammation and an innate source of IL-13 that can directly induce AHR in the absence of IL-13 producing CD4(+) T cells. These data highlight nuocytes as an important new consideration in the development of future allergic asthma therapy. PMID- 22079493 TI - Molecular characterization and expression analysis of two new C-reactive protein genes from common carp (Cyprinus carpio). AB - C-Reactive protein (CRP) plays an important role in the acute phase response. Transcripts encoding two new CRP-like molecules (ccCRP1 and ccCRP2) from European common carp have been characterized which has enabled seven CRP-like genes to be identified in zebrafish. 79.3% (ccCRP1) and 74.5% (ccCRP2) identity to CRP from East-Asian common carp occurs and fish CRP genes form a distinct clade. ccCRP2 gene organization comprises four exons and three introns, in contrast to the two exons/one intron organization of mammalian CRP genes. Gene expression assays showed both ccCRP-like molecules are constitutively expressed in liver, skin, gill, gut, muscle, kidney, spleen and blood. Protein levels of ccCRP in serum and spleen were significantly different from other organs analyzed, and levels were greatest in the liver. It is proposed that the two carp CRP genes defined differ in their expression profiles which may suggest differences in their biological activities. PMID- 22079494 TI - Excitation, inhibition, local oscillations, or large-scale loops: what causes the symptoms of schizophrenia? AB - What causes the positive, negative, and cognitive symptoms of schizophrenia? The importance of circuits is underscored by the finding that no single gene contributes strongly to the disease. Thus, some circuit abnormality to which many proteins can contribute is the likely cause. There are several major hypotheses regarding the circuitry involved: first, a change in the balance of excitation/inhibition in the prefrontal cortex (PFC); second, abnormal EEG oscillations in the gamma range; third, an increase in theta/delta EEG power related to changes in the thalamus (particularly midline nuclei); fourth, hyperactivity in the hippocampus and consequent dopamine hyperfunction; and fifth, deficits in corollary discharge. Evidence for these hypotheses will be reviewed. PMID- 22079495 TI - Episodic memory on the path to Alzheimer's disease. AB - This review is focused on specific circuits of the medial temporal lobe that have become better understood in recent years for their computational properties contributing to episodic memory and to memory impairment associated with aging and other risk for AD. The layer II neurons in the entorhinal cortex and their targets in the dentate gyrus and CA3 region of hippocampus comprise a system that rapidly encodes representations that are distinct from prior memories. Frank neuron loss in the entorhinal cortex is specific for AD, and related structural and functional changes across the network comprised of the entorhinal cortex and the dentate/CA3 regions hold promise for predicting progression on the path to AD. PMID- 22079496 TI - Multi-scale simulations of field ion microscopy images--image compression with and without the tip shank. AB - Multi-scale simulations of field ion microscopy images of faceted and hemispherical samples are performed using a 3D model. It is shown that faceted crystals have compressed images even in cases with no shank. The presence of the shank increases the compression of images of faceted crystals quantitatively in the same way as for hemispherical samples. It is hereby proven that the shank does not influence significantly the local, relative variations of the magnification caused by the atomic-scale structure of the sample. PMID- 22079497 TI - A software tool for automatic analysis of selected area diffraction patterns within Digital MicrographTM. AB - A software package "SADP Tools" is developed as a complementary diffraction pattern analysis tool. The core program, called AutoSADP, is designed to facilitate automated measurements of d-spacing and interplaner angles from TEM selected area diffraction patterns (SADPs) of single crystals. The software uses iterative cross correlations to locate the forward scattered beam position and to find the coordinates of the diffraction spots. The newly developed algorithm is suitable for fully automated analysis and it works well with asymmetric diffraction patterns, off-zone axis patterns, patterns with streaks, and noisy patterns such as Fast Fourier transforms of high-resolution images. The AutoSADP tool runs as a macro for the Digital Micrograph program and can determine d spacing values and interplanar angles based on the pixel ratio with an accuracy of better than about 2%. PMID- 22079499 TI - Inspection of collapse cause of Sampoong Department Store. AB - On June 29, 1995, the Sampoong Department Store in Seoul, South Korea, completely collapsed. It was a five story reinforced concrete (RC) building with underground 4 floors and was built using a technique called "flat slab construction". The collapse is the largest peacetime disaster in South Korean history - 502 people died, 6 missing, and 937 sustained injuries. The Sampoong Department Store was completed in late 1989, and it opened to the public on July 7, 1990, attracting an estimated 40,000 people per day during the building's 5 years in service. After the collapse, intense investigation was conducted to find out the direct causes of the collapse through (1) survey on the present collapse situation and ground condition, (2) strength test of the concrete and steel collected at the site, (3) design documents and construction/management reports, and (4) structural analysis. The investigation revealed that the Sampoong Department Store collapsed because so many direct and indirect causes such as flaws in design phase and mistakes in construction and management process were overlapped. PMID- 22079498 TI - Detection of polybrominated biphenyl ethers (PBDEs) in pediatric hair as a tool for determining in utero exposure. AB - INTRODUCTION: Cryptorchidism, or undescended/maldescended testis, is the most common birth defect of male genitalia. Its prevalence has been increasing over the past few decades. This may be due to an increase in the prevalence of anti androgenic chemicals such as polychlorinated biphenyls, organochloride pesticides, plasticizers and fungicides. A newer group of chemicals, brominated flame retardants (BFRs), are being implicated as endocrine-disrupting chemicals. These chemicals are used worldwide in polymers that are incorporated into a variety of consumer products (e.g., textile, computers and televisions, insulating foam, electrical equipment and kitchen appliances). In order to quantify BFRs we introduce the use of hair levels of polybrominated diphenyl esters (PBDEs) as biomarkers of systemic exposure. This approach will allow for the estimation of in utero BFR exposure, in the process of evaluating the potential link between the incidence of cryptorchidism in newborn males and level of exposure of the pregnant mother to environmentally relevant BFRs. For that end we have developed a GC/MS assay in which children's hair is analyzed for the presence of polybrominated biphenyl ethers (PBDEs). METHODS: In this pilot, 10 40mg of hair from 24 children (12 newborn and 12 from children 1 to 15 years) was extracted overnight at 40 degrees C with 4N HCl and hexane (4:1). The samples were eluted from 2g NaSO(4):2g Florisil SPE columns with 8mL hexane. Dried samples are reconstituted with anhydrous isooctane and injected onto a GC/MS and analyzed for BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183 and BDE 209. RESULTS: PBDEs were detected in all of the newborn and child hair. The SigmaPBDE ranged from 0.038 to 1.01pg/mg newborn hair and from 0.208 to 2.695ng/mg child hair. The most abundant PBDE in newborn hair was BDE-153 while in child hair the variable PBDEs were BDE-47 and BDE-99. The highest molecular weight congener BDE-209 was detected in 10/24 pediatric hair samples. The LOQ is 0.0625pg/mg (BDE-209 0.625pg/mg) and the efficiency of extraction was between 70 and 90%. CONCLUSION: This GC/MS method is sufficiently sensitive to detect the presence of all 8 PBDE congeners tested in as little as 10mg of pediatric hair. The results show that PBDEs are present in newborn hair, making this matrix useful in examining in utero exposure to PBDEs and linking it to cryptorchidism. PMID- 22079500 TI - Single genotypes underestimate the prevalence of antiretroviral resistance in patients with perinatally acquired HIV. PMID- 22079501 TI - Procalcitonin improves the differentiation between infectious and cryptogenic/secondary organizing pneumonia. PMID- 22079502 TI - Short course amphotericin B with high dose fluconazole for HIV-associated cryptococcal meningitis. AB - OBJECTIVE: To define more rapidly effective initial antifungal regimens sustainable in resource-constrained settings. METHODS: Cohort study in SW Uganda: Thirty HIV-seropositive, antiretroviral therapy-naive, patients with first episode cryptococcal meningitis were treated with high dose fluconazole (1200 mg/d for 2 weeks, then 800 mg/d until ART started) plus amphotericin B (AmB, 1 mg/kg/d), with routine normal saline and potassium supplementation, for the initial 5 days. Outcome measures were early fungicidal activity (EFA), determined by serial quantitative CSF cultures, safety, and mortality. RESULTS: EFA was 0.30 +/- 0.11 log CFU/day calculated over the first 2 weeks of treatment, with no reduction in the rate of clearance between days 5 and 14. There was no grade IV hypokalemia or elevated creatinine, and no grade III or IV anemia or elevation of ALT. AmB or high dose fluconazole were not stopped early in any patient. Mortality was 23% at 2, and 28% at 10 weeks. CONCLUSIONS: Short course AmB was associated with rapid clearance of infection and was well-tolerated, suggesting it could be used safely in many centres currently relying on fluconazole monotherapy. Phase III trials are needed in African centres to compare short course with the standard 2-week course of AmB. PMID- 22079503 TI - Glucose starvation stimulates Zn2+ toxicity in cultures of cerebellar granule neurons. AB - Zinc chloride (0.02 mM, 3h) did not have any influence on the survival of cerebellar granule neurons (CGNs) incubated in balanced salt solution (BSS). However, in the absence of glucose ZnCl(2) caused severe neuronal damage, decreasing cell survival to 12+/-2%. Either the blockade of ionotropic glutamate NMDA-receptors with MK-801 or APV or supplementation the medium with ruthenium red (mitochondrial Ca(2+) uniporter blocker) almost entirely protected CGNs from the toxic effect of ZnCl(2) during glucose deprivation (GD). However, NBQX (AMPA/kainate glutamate receptor blocker) did not show protective effect. Measurements of intracellular calcium ions concentration using fluorescent probe (Fluo-4 AM) and zinc ions (FluoZin-3AM) demonstrated that 1.5h-exposure to GD induced intensive increase of Fluo-4 fluorescence and small increase of FluoZin-3 fluorescence in neurons. The supplementation of medium with ZnCl(2) caused equal increase of FluoZin-3 fluorescence at both GD and normoglycemia, whereas the potentiation of Fluo-4 fluorescence by zinc was observed only under GD and could be prevented by MK-801. However, neither MK-801 nor NBQX could influence [Zn(2+)](i) increase caused by zinc addition under GD, while ruthenium red did cause significant increase of [Zn(2+)](i). This data implies that zinc ions during GD induce an additional overload of CGNs with calcium ions that get transported through activated NMDA-channel. Zinc and calcium ions accumulate in mitochondria and amplify individual destructive action on these organelles leading to neuronal death. PMID- 22079504 TI - Single pulse TMS induced disruption to right and left parietal cortex on addition and multiplication. AB - Whether or not mathematical operations are dependent on verbal codes in left hemisphere areas - particularly the left intraparietal sulcus - remains an issue of intense debate. Using single pulse transcranial magnetic stimulation directed at horizontal and ventral regions of the left and right intraparietal sulcus, we examined disruption to reaction times in simple addition and multiplication. Results indicate that these two operations differ in the pattern of lateralization across time for the two areas studied. These show that computational efficiency is not specifically dependent on left hemisphere regions and, in particular, that efficiency in multiplication is dependent on the ventral region of the intraparietal sulcus in the right hemisphere considered to be critical for motion representation and automatization. PMID- 22079505 TI - Time course of word production in fast and slow speakers: a high density ERP topographic study. AB - The transformation of an abstract concept into an articulated word is achieved through a series of encoding processes, which time course has been repeatedly investigated in the psycholinguistic and neuroimaging literature on single word production. The estimates of the time course issued from previous investigations represent the timing of process duration for mean processing speed: as production speed varies significantly across speakers, a crucial question is how the timing of encoding processing varies with speed. Here we investigated whether between subjects variability in the speed of speech production is distributed along all encoding processes or if it is accounted for by a specific processing stage. We analysed event-related electroencephalographical (ERP) correlates during overt picture naming in 45 subjects divided into three speed subgroups according to their production latencies. Production speed modulated waveform amplitudes in the time window ranging from about 200 to 350 ms after picture presentation and the duration of a stable electrophysiological spatial configuration in the same time period. The remaining time windows from picture onset to 200 ms before articulation were unaffected by speed. By contrast, the manipulation of a psycholinguistic variable, word age-of-acquisition, modulated ERPs in all speed subgroups in a different and later time period, starting at around 400 ms after picture presentation, associated with phonological encoding processes. These results indicate that the between-subject variability in the speed of single word production is principally accounted for by the timing of a stable electrophysiological activity in the 200-350 ms time period, presumably associated with lexical selection. PMID- 22079506 TI - Single-trial magnetoencephalography signals encoded as an unfolding decision process. AB - The model of a stochastic decision process unfolding in motor and premotor regions of the brain was encoded in single-trial magnetoencephalographic (MEG) recordings while ten healthy subjects performed a sensorimotor Reaction Time (RT) task. The duration of single-trial MEG signals preceding the motor response, recorded over the motor cortex contralateral to the responding hand, co-varied with RT across trials according to the model's prediction. Furthermore, these signals displayed the same properties of a "rising-to-a-fixed-threshold" decision process as posited by the model and observed in the activity of single neurons in the primate cortex. The present findings demonstrate that non-averaged, single trial MEG recordings can be used to test models of cognitive processes, like decision-making, in humans. PMID- 22079507 TI - Inflammation selectively enhances amygdala activity to socially threatening images. AB - Although social withdrawal is a prominent symptom of sickness, the mechanisms associated with this behavioral change remain unclear. In animals, the amygdala is a key neural region involved in sickness-induced social withdrawal. Consistent with this, in humans, heightened amygdala activity to negative social cues is associated with social avoidance tendencies. Based on these findings, we investigated whether an experimental inflammatory challenge selectively increased amygdala activity to socially threatening images as well as whether this activity related to feelings of social disconnection. Thirty-nine participants were randomly assigned to receive either placebo or low-dose endotoxin, which increases inflammatory activity. Pro-inflammatory cytokines were assessed at 7 hourly time points via blood draws; self-reported feelings of social disconnection and physical sickness symptoms were assessed hourly as well. Two hours post-injection, participants underwent an fMRI procedure to assess amygdala reactivity during the presentation of socially threatening images (fear faces) as well as non-socially threatening images (guns), socially non-threatening images (happy faces), and non-social, non-threatening images (household objects). Endotoxin led to greater amygdala activity in response to socially threatening vs. all other types of images. No such differences were found for placebo participants. Additionally, increased amygdala activity in endotoxin participants during the viewing of socially vs. non-socially threatening images was associated with increased feelings of social disconnection. These findings highlight the amygdala as a neural region that may be important for sickness-induced social withdrawal. The implications of amygdalar involvement in sickness-induced social withdrawal are discussed. PMID- 22079508 TI - Generation of continuous packed bed reactor with PVA-alginate blend immobilized Ochrobactrum sp. DGVK1 cells for effective removal of N,N-dimethylformamide from industrial effluents. AB - Effective removal of dimethylformamide (DMF), the organic solvent found in industrial effluents of textile and pharma industries, was demonstrated by using free and immobilized cells of Ochrobactrum sp. DGVK1, a soil isolate capable of utilizing DMF as a sole source of carbon, nitrogen. The free cells have efficiently removed DMF from culture media and effluents, only when DMF concentration was less than 1% (v/v). Entrapment of cells either in alginate or in polyvinyl alcohol (PVA) failed to increase tolerance limits. However, the cells of Ochrobactrum sp. DGVK1 entrapped in PVA-alginate mixed matrix tolerated higher concentration of DMF (2.5%, v/v) and effectively removed DMF from industrial effluents. As determined through batch fermentation, these immobilized cells have retained viability and degradability for more than 20 cycles. A continuous packed bed reactor, generated by using PVA-alginate beads, efficiently removed DMF from industrial effluents, even in the presence of certain organic solvents frequently found in effluents along with DMF. PMID- 22079509 TI - An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. AB - BACKGROUND & AIMS: Despite immunoprophylaxis, mother to child transmission (MTCT) of hepatitis B virus (HBV) still occurs in infants born to hepatitis B surface antigen (HBsAg)-positive mothers. We analyzed methods of risk assessment and interventions for MTCT. METHODS: We reviewed 63 articles and abstracts published from 1975-2011 that were relevant to MTCT; articles were identified using the PubMed bibliographic database. RESULTS: Administration of HB immunoglobulin and HB vaccine to infants at birth (within 12 hours), followed by 2 additional doses of vaccines within 6-12 months, prevented approximately 95% of HBV transmission from HBsAg-positive mothers to their infants. However, HBV was still transmitted from 8%-30% of mothers with high levels of viremia. It is important to assess the risk for MTCT and identify mothers who are the best candidates for intervention. The most important risk factor is maternal level of HBV DNA >200,000 IU (10(6) copies)/mL; other factors include a positive test result for the HB e antigen, pregnancy complications such as threatened preterm labor or prolonged labor, and failure of immunoprophylaxis in prior children. Antiviral therapy during late stages of pregnancy is the most effective method to reduce transmission from mothers with high levels of viremia, but elective cesarean section might also be effective. Antepartum administration of HB immunoglobulin, giving infants a double dose of HB vaccine, or avoiding breastfeeding had no impact on MTCT. CONCLUSIONS: HBsAg-positive mothers should be assessed for risk of MTCT, and infants should receive immunoprophylaxis. Pregnant women with levels of HBV DNA >200,000 IU/mL should be considered for strategies to reduce the risk for MTCT. We propose an algorithm for risk assessment and patient management that is based on a review of the literature and the opinion of a panel of physicians with expertise in preventing MTCT. PMID- 22079510 TI - Spontaneous intramural hematoma of colon. PMID- 22079511 TI - Tinkering with a tarnished technique: isn't it time to abandon celiac plexus blockade for the treatment of abdominal pain in chronic pancreatitis? PMID- 22079512 TI - Baclofen improves symptoms and reduces postprandial flow events in patients with rumination and supragastric belching. AB - BACKGROUND & AIMS: In patients with clinically suspected rumination, esophageal impedance manometry differentiates episodes of rumination (involuntary straining with intragastric pressure increases) from aerophagia/supragastric belching. Treatment options are limited and focused on behavioral therapy. Baclofen, an agonist of the gamma-aminobutyric acid B receptor, increases lower esophageal sphincter pressure and decreases swallowing rate. We investigated its effects in these patients. METHODS: High-resolution manometry-impedance recordings were taken from 12 patients (8 women; mean age, 45 years; range, 18-89 years) with clinically suspected rumination or supragastric belching before and during treatment with baclofen (10 mg, 3 times daily). After 30 minutes of recordings, patients received a 1000-kcal solid meal; recordings were then continued for 1 hour. Patients were asked to register symptoms with an event marker. The number of symptoms registered and number and type of flow events were compared before and during treatment. RESULTS: An average of 20 symptom markers (range, 14-34) were recorded at baseline (10 [range, 4-25] for belching and 9 [range, 0-11] for regurgitation). This was significantly reduced to 6 (range, 2-22) (3 [range, 1 15] for belching and 1 [range, 0-13] for regurgitation) during baclofen treatment (P = .01). The number of flow events (473 at baseline [42 reflux, 192 rumination, 188 supragastric belching, and 42 aerophagia]) was significantly reduced to 282 (32 reflux, 99 rumination, 123 supragastric belching, and 13 aerophagia) during baclofen therapy (P = .02). The reduction in flow events correlated with the increase in lower esophageal sphincter pressure (r = -0.62; P = .03) and reduction in swallowing frequency (r = 0.64; P = .02). CONCLUSIONS: Baclofen is an effective treatment for patients with rumination or supragastric belching/aerophagia. PMID- 22079513 TI - Telomerase and idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is the most common manifestation of telomere mediated disorders. Germline mutations in the essential telomerase genes, hTERT and hTR, are the causal genetic defect in up to one-sixth of pulmonary fibrosis families. The presence of telomerase mutations in this subset is significant for clinical decisions as affected individuals can develop extra-pulmonary complications related to telomere shortening such as bone marrow failure and cryptogenic liver cirrhosis. There is also evidence that IPF is an ancestral manifestation of autosomal dominant telomere syndromes where, with successive generations, the disease evolves from pulmonary fibrosis into a bone marrow failure-predominant disorder, defining a unique form of genetic anticipation. Here I review the significance of telomere defects for understanding the genetics, disease patterns and pathophysiology of IPF. The importance of this diagnosis for patient care decisions will also be discussed. PMID- 22079514 TI - [Results and reflections of the Scientific Committee of the XXVIII Conference of the Spanish Society of Quality in Healthcare]. AB - OBJECTIVES: To determine whether the objectives entrusted to the Scientific Committee (SC) of the 28th National Conference have been met, and to determine whether the results differed from those of previous conferences. METHODS: A chronological description of the work of the SC and a comparison with the results of the previous two Conferences of the Spanish Society for Quality in health care (SSQHC). RESULTS: A total of 869 papers were submitted, of which 32.6% corresponded to the area of patient safety. Galicia was the community that presented more communications (28%), followed by Catalonia (12.9%) and Murcia (10.9%). CONCLUSIONS: The methodology used by the SC helped in the compliance with the deadlines in the SSQHC Conference manual and contributed to achieve its objectives. Abstract presentations were classified accordingly to their quality. The Conference has been consolidated as a multidisciplinary meeting with participation by doctors, nurses, managers and open to the Latin-American community. PMID- 22079515 TI - Dodecafluoropentane emulsion decreases infarct volume in a rabbit ischemic stroke model. AB - PURPOSE: To assess the efficacy of dodecafluoropentane emulsion (DDFPe), a nanodroplet emulsion with significant oxygen transport potential, in decreasing infarct volume in an insoluble-emboli rabbit stroke model. MATERIALS AND METHODS: New Zealand White rabbits (N = 64; weight, 5.1 +/- 0.50 kg) underwent angiography and received embolic spheres in occluded internal carotid artery branches. Rabbits were randomly assigned to groups in 4-hour and 7-hour studies. Four-hour groups included control (n = 7, embolized without treatment) and DDFPe treatment 30 minutes before stroke (n = 7), at stroke onset (n = 8), and 30 minutes (n = 5), 1 hour (n = 7), 2 hours (n = 5), or 3 hours after stroke (n = 6). Seven-hour groups included control (n = 6) and DDFPe at 1 hour (n = 8) and 6 hours after stroke (n = 5). DDFPe dose was a 2% weight/volume intravenous injection (0.6 mL/kg) repeated every 90 minutes as time allowed. After euthanasia, infarct volume was determined by vital stains on brain sections. RESULTS: At 4 hours, median infarct volume decreased for all DDFPe treatment times (pretreatment, 0.30% [P = .004]; onset, 0.20% [P = .004]; 30 min, 0.35% [P = .009]; 1 h, 0.30% [P = .01]; 2 h, 0.40% [P = .009]; and 3 h, 0.25% [P = .003]) compared with controls (3.20%). At 7 hours, median infarct volume decreased with treatment at 1 hour (0.25%; P = .007) but not at 6 hours (1.4%; P = .49) compared with controls (2.2%). CONCLUSIONS: Intravenous DDFPe in an animal model decreases infarct volumes and protects brain tissue from ischemia, justifying further investigation. PMID- 22079516 TI - Radioembolization versus standard care of hepatic metastases: comparative retrospective cohort study of survival outcomes and adverse events in salvage patients. AB - PURPOSE: To retrospectively evaluate the safety and survival of patients with chemotherapy-refractory liver metastases treated with yttrium-90 ((90)Y) resin microspheres, and to compare survival in this patient group versus survival after standard/supportive care to assess whether radioembolization contributes to survival gains in the salvage setting. MATERIALS AND METHODS: While 339 patients with chemotherapy-refractory liver metastases underwent (90)Y microspheres radioembolization at a single institution between 2006 and 2011, 51 patients were referred back to their treating physician for conservative treatment or best supportive care. Adverse events were assessed at the time of treatment and at 1 and 3 months after treatment. Overall survival (OS) was calculated by the Kaplan Meier method for the radioembolization cohort (as a whole and according to two subcohorts: patients with colorectal primary cancer and patients with all other primary cancers, eg, breast or neuroendocrine) and the standard-care cohort. RESULTS: The median OS after (90)Y radioembolization (339 patients) was 12.0 months, versus 6.3 months for the standard-care cohort (51 patients; P < .001). The median OS times for the two subcohorts were 11.9 months and 12.7 months, respectively. At the 3-month follow-up, the incidence of more serious adverse events was low, with 11 cases (3%) of ulceration, 10 cases (2.9%) of radiation induced liver disease, and six complications (1.8%) involving the gallbladder (eg, cholecystitis). CONCLUSIONS: The present study suggests that radioembolization shows promise as an effective and safe treatment for patients with chemotherapy-refractory hepatic metastases and improves overall survival in a select population of patients in a salvage setting compared with best supportive care alone. PMID- 22079517 TI - On the conjunction fallacy and the meaning of and, yet again: a reply to Hertwig, Benz, and Krauss (2008). AB - In this paper we question the theoretical tenability of Hertwig, Benz, and Krauss's (2008) (HBK) argument that responses commonly taken as manifestations of the conjunction fallacy should be instead considered as reflecting "reasonable pragmatic and semantic inferences" because the meaning of and does not always coincide with that of the logical operator ?. We also question the relevance of the experimental evidence that HBK provide in support of their argument as well as their account of the pertinent literature. Finally, we report two novel experiments in which we employed HBK's procedure to control for the interpretation of and. The results obtained overtly contradict HBK's data and claims. We conclude with a discussion on the alleged feebleness of the conjunction fallacy, and suggest directions that future research on this topic might pursue. PMID- 22079518 TI - Visualizing the effect of hypoxia on fluorescence kinetics in living HeLa cells using the fluorescent ubiquitination-based cell cycle indicator (Fucci). AB - Fluorescent proteins are widely used for the direct visualization of events such as gene expression and subcellular localization in mammalian cells. It is well established that oxygen is required for formation of functional chromophore; however, the effect of hypoxia on fluorescence emission has rarely been studied. For this purpose, under hypoxic conditions, we investigated the kinetics of red and green fluorescence in HeLa cells from two fluorescent proteins, monomeric Kusabira Orange 2 (mKO2) and monomeric Azami Green (mAG), respectively, using the fluorescent ubiquitination-based cell cycle indicator (Fucci). In this system, cells in G1 or other phases emit red or green fluorescence, respectively. We found that hypoxia abrogated both red and green fluorescence about ~10h after the treatment, although their protein levels were almost maintained. The treatment did not significantly affect fluorescence in cells constitutively expressing the same fluorescent proteins lacking the ubiquitin ligase-binding domains. The abrogation of fluorescence resulted from a combination of ubiquitination dependent degradation of pre-existing functional proteins during specific cell cycle phases, and the expression of newly synthesized non-fluorescent proteins containing non-oxidized chromophore during hypoxic treatment. Indeed, non fluorescent cells after hypoxic treatment gradually developed fluorescence after reoxygenation in the presence of cycloheximide; kinetics of recovery were much faster for mAG than for mKO2. Using the Fucci system, we could clearly visualize for the first time the effect of hypoxia on the fluorescence kinetics of proteins expressed in living mammalian cells. PMID- 22079519 TI - The interaction of an azo compound with a surfactant and ion pair adsorption to solid phases. AB - The adsorption of SPADNS (trisodium salt of 2-(p-sulfophenylazo)-1,8 dihydroxynaphthalene-3,6-disulfonic acid) onto resins XAD 2, XAD 7 and silica gel was studied in the presence and in the absence of the cationic surfactant CTAB (cetyl trimethylammonium bromide). At a ratio of 2.5 CTAB to 1 SPADNS, the surfactant caused a marked increase in SPADNS adsorption. The experimental results for adsorption versus time were applied on the basis of three kinetic models (pseudo-first-order Lagergren, pseudo-second-order, and intraparticle diffusion). The interaction between CTAB and SPADNS was investigated using spectrophotometric, conductometric, and computational techniques. Theoretical results point to the formation of an ion pair between CTAB and SPADNS that influences the solution spectra, in agreement with conductometric and spectrophotometric data. PMID- 22079520 TI - Cobalt oxide silica membranes for desalination. AB - This work shows for the first time the potential of cobalt oxide silica (CoO(x)Si) membranes for desalination of brackish (1 wt.% NaCl), seawater (3.5 wt.% NaCl) and brine (7.5-15 wt.% NaCl) concentrations at feed temperatures between 25 and 75 degrees C. CoO(x)Si xerogels were synthesised via a sol-gel method including TEOS, cobalt nitrate hydrate and peroxide. Initial hydrothermal exposure (<2 days) of xerogels prepared with various pH (3-6) resulted in densification of the xerogel via condensation reactions within the silica matrix, with the xerogel synthesised at pH 5 the most resistant. Subsequent exposure was not found to significantly alter the pore structure of the xerogels, suggesting they were hydrostable and that the pore sizes remained at molecular sieving dimensions. Membranes were then synthesised using identical sol-gel conditions to the xerogel samples and testing showed that elevated feed temperatures resulted in increased water fluxes, whilst increasing the saline feed concentration resulted in decreased water fluxes. The maximum flux observed was 1.8 kg m(-2) h( 1) at 75 degrees C for a 1 wt.% NaCl feed concentration. The salt rejection was consistently in excess of 99%, independent of either the testing temperature or salt feed concentration. PMID- 22079521 TI - Uniform distribution of TiO2 nanocrystals on reduced graphene oxide sheets by the chelating ligands. AB - Reduced graphene oxide-TiO(2) hybrids were successfully prepared by the hydrothermal approach using triethanolamine and acetylacetone as the chelating agents. Without any additive, large aggregated TiO(2) clusters were randomly distributed dominantly at the edge and less on the basil plane of coagulated reduced graphene oxide (RGO) layers. The presence of chelating ligands remarkably facilitated the selective growth and regular spread of TiO(2) nanocrystals onto individually exfoliated RGO sheet. Such sandwich-like structure with stronger coupling and chemical interaction resulted in the surface area increase, the rearrangement of energy level, the enhanced concentration of oxygen vacancies, leading to much higher adsorbability and photocatalytic degradation of Rhodamine B under both UV and visible irradiations. These RGO-TiO(2) hybrid systems are potentially beneficial for widely practical applications in air/water purification, electronic devices, batteries, solar cells or supercapacitors. PMID- 22079522 TI - Dynamic control of gold nanoparticle morphology in a microchannel flow reactor by glucose reduction in aqueous sodium hydroxide solution. AB - Continuous flow synthesis of gold nanoparticles was demonstrated using a microchannel reactor with glucose reduction in aqueous alkaline medium. Particle size, morphology, and visual/optical properties of the dispersion liquid were controlled dynamically by tuning of the rate of NaOH addition. Characteristic star-like nanoparticles formed spontaneously as a quasi-stable state, but they changed the morphology to round shape and showed spectral change over time. PMID- 22079524 TI - The effects of gait impairment with and without freezing of gait in Parkinson's disease. AB - OBJECTIVE: To compare the effects of gait impairment without freezing of gait (FOG) versus FOG without gait impairment in Parkinson's disease (PD) on disability and quality of life. BACKGROUND: FOG is frequently characterized as the major cause of gait-related disability in PD. However, gait impairment may also result from other PD symptoms including slowing, motor asymmetry, gait variability, dystonia or stooped posture. METHODS: The Unified Parkinson's Disease Rating Scale (UPDRS), Older Americans Resources and Services Disability Scale (OARS) and the SF-12 Health Status Survey were used to evaluate patients with PD. Responses to UPDRS Items #14 (Freezing) and # 29 (Gait) were used to create 4 subgroups: 1) No FOG or gait impairment, 2) FOG, no gait impairment, 3) Gait impairment, no FOG, and 4) Both FOG and gait impairment. Disease severity, disability, and quality of life were compared across the subgroups with ANOVAs, and between subgroups with t-tests. RESULTS: 916 PD patients were divided into 4 subgroups based on their gait and freezing score (#1: n = 213, #2: n = 41, #3: n = 323 and #4: n = 339). Total UPDRS progressively increased from Group 1 through Group 4 (1 = 25.2, 2 = 33.7, 3 = 39.2, 4 = 59.2; p < 0.001). Motor UPDRS also progressively increased (1 = 17.4, 2 = 19.7, 3 = 26.9, 4 = 36.5; p < 0.0001). Similarly, disability and health-related quality of life progressively increased from Group 1 through Group 4 (Total OARS: 1 = 15.3, 2 = 17.2, 3 = 18.9, 4 = 28.4; p < 0.001). Group 3 (Gait impairment, no FOG) showed greater disease severity than Group 2 (FOG, no gait impairment; Total and Motor UPDRS; p < 0.05), but the difference did not reach significance for disability or quality of life. CONCLUSIONS: Gait impairment without FOG was associated with greater disease severity than FOG without gait impairment. The combination of gait impairment and FOG was associated with the greatest disease severity and disability. These results show differential effects of diverse features of gait impairment in PD and demonstrate the importance of gait features unrelated to freezing. PMID- 22079523 TI - Rates of brain atrophy and clinical decline over 6 and 12-month intervals in PSP: determining sample size for treatment trials. AB - Imaging biomarkers are useful outcome measures in treatment trials. We compared sample size estimates for future treatment trials performed over 6 or 12-months in progressive supranuclear palsy using both imaging and clinical measures. We recruited 16 probable progressive supranuclear palsy patients that underwent baseline, 6 and 12-month brain scans, and 16 age-matched controls with serial scans. Disease severity was measured at each time-point using the progressive supranuclear palsy rating scale. Rates of ventricular expansion and rates of atrophy of the whole brain, superior frontal lobe, thalamus, caudate and midbrain were calculated. Rates of atrophy and clinical decline were used to calculate sample sizes required to power placebo-controlled treatment trials over 6 and 12 months. Rates of whole brain, thalamus and midbrain atrophy, and ventricular expansion, were increased over 6 and 12-months in progressive supranuclear palsy compared to controls. The progressive supranuclear palsy rating scale increased by 9 points over 6-months, and 18 points over 12-months. The smallest sample size estimates for treatment trials over 6-months were achieved using rate of midbrain atrophy, followed by rate of whole brain atrophy and ventricular expansion. Sample size estimates were further reduced over 12-month intervals. Sample size estimates for the progressive supranuclear palsy rating scale were worse than imaging measures over 6-months, but comparable over 12-months. Atrophy and clinical decline can be detected over 6-months in progressive supranuclear palsy. Sample size estimates suggest that treatment trials could be performed over this interval, with rate of midbrain atrophy providing the best outcome measure. PMID- 22079525 TI - Cross-species investigation of the functions of the Rhodobacter PufX polypeptide and the composition of the RC-LH1 core complex. AB - In well-characterised species of the Rhodobacter (Rba.) genus of purple photosynthetic bacteria it is known that the photochemical reaction centre (RC) is intimately-associated with an encircling LH1 antenna pigment protein, and this LH1 antenna is prevented from completely surrounding the RC by a single copy of the PufX protein. In Rba. veldkampii only monomeric RC-LH1 complexes are assembled in the photosynthetic membrane, whereas in Rba. sphaeroides and Rba. blasticus a dimeric form is also assembled in which two RCs are surrounded by an S-shaped LH1 antenna. The present work established that dimeric RC-LH1 complexes can also be isolated from Rba. azotoformans and Rba. changlensis, but not from Rba. capsulatus or Rba. vinaykumarii. The compositions of the monomers and dimers isolated from these four species of Rhodobacter were similar to those of the well characterised RC-LH1 complexes present in Rba. sphaeroides. Pigment proteins were also isolated from strains of Rba. sphaeroides expressing chimeric RC-LH1 complexes. Replacement of either the Rba. sphaeroides LH1 antenna or PufX with its counterpart from Rba. capsulatus led to a loss of the dimeric form of the RC LH1 complex, but the monomeric form had a largely unaltered composition, even in strains in which the expression level of LH1 relative to the RC was reduced. The chimeric RC-LH1 complexes were also functional, supporting bacterial growth under photosynthetic conditions. The findings help to tease apart the different functions of PufX in different species of Rhodobacter, and a specific protein structural arrangement that allows PufX to fulfil these three functions is proposed. PMID- 22079526 TI - Elimination of onchocerciasis from Africa: possible? AB - Human onchocerciasis, a parasitic disease found in 28 African countries, six Latin American countries and Yemen, causes blindness and severe dermatological problems. In 1987, efforts to control this infection shifted from vector approaches to include the mass distribution of ivermectin - a drug donated by Merck & Co. for disease control in Africa and for disease elimination in the Americas. Currently, almost 25 years later, with the Americas being highly successful and now approaching elimination, new evidence points towards the possibility of successful elimination in Africa. We suggest several major changes in the programmatic approach that through focused goal-directed effort could achieve global elimination of onchocerciasis by 2025. PMID- 22079527 TI - Fear conditioning occludes late-phase long-term potentiation at thalamic input synapses onto the lateral amygdala in rat brain slices. AB - Late-phase long-term potentiation (L-LTP) of excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala (T-LA synapses) has been proposed as a cellular substrate for long-term fear memory. This notion is evidenced primarily by previous reports in which the same pharmacological treatments block both T-LA L-LTP and the consolidation of fear memory. In this study, we report that fear conditioning occludes L-LTP at T-LA synapses in brain slices prepared after fear memory consolidation. L-LTP was restored either when synaptic depotentiation was induced prior to L-LTP induction in brain slices prepared from conditioned rats or when brain slices were prepared from conditioned rats that had been exposed to subsequent fear extinction, which is a behavior paradigm known to induce in vivo synaptic depotentiation at T-LA synapses. These results suggest that fear conditioning recruits L-LTP-like mechanisms that are reversible and saturable at T-LA synapses. PMID- 22079528 TI - Radiotherapy with curative intent for lung cancer: a continuing success story. PMID- 22079529 TI - Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series. AB - BACKGROUND AND PURPOSE: To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena). MATERIAL AND METHODS: Fifty six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases. RESULTS: Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively. CONCLUSION: Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP. PMID- 22079530 TI - Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury. AB - BACKGROUND: We have demonstrated that soy isoflavones radiosensitize cancer cells. Prostate cancer patients receiving radiotherapy (RT) and soy tablets had reduced radiation toxicity to surrounding organs. We have now investigated the combination of soy with RT in lung cancer (NSCLC), for which RT is limited by radiation-induced pneumonitis. METHODS: Human A549 NSCLC cells were injected i.v. in nude mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with left lung RT at 12 Gy and with oral soy treatments at 1mg/day for 30 days. Lung tissues were processed for histology. RESULTS: Compared to lung tumor nodules treated with soy isoflavones or radiation, lung tissues from mice treated with both modalities showed that soy isoflavones augmented radiation-induced destruction of A549 lung tumor nodules leading to small residual tumor nodules containing degenerating tumor cells with large vacuoles. Soy isoflavones decreased the hemorrhages, inflammation and fibrosis caused by radiation in lung tissue, suggesting protection of normal lung tissue. CONCLUSIONS: Soy isoflavones augment destruction of A549 lung tumor nodules by radiation, and also mitigate vascular damage, inflammation and fibrosis caused by radiation injury to normal lung tissue. Soy could be used as a non-toxic complementary approach to improve RT in NSCLC. PMID- 22079531 TI - The role of CXC chemokines in the transition of chronic inflammation to esophageal and gastric cancer. AB - Chronic inflammation may increase the risk to develop cancer, for instance esophagitis or gastritis may lead to development of esophageal or gastric cancer, respectively. The key molecules attracting leukocytes to local inflammatory sites are chemokines. We here provide a systematic review on the impact of CXC chemokines (binding the receptors CXCR1, CXCR2, CXCR3 and CXCR4) on the transition of chronic inflammation in the upper gastrointestinal tract to neoplasia. CXCR2 ligands, including GRO-alpha,beta,gamma/CXCL1,2,3, ENA-78/CXCL5 and IL-8/CXCL8 chemoattract pro-tumoral neutrophils. In addition, angiogenic CXCR2 ligands stimulate the formation of new blood vessels, facilitating tumor progression. The CXCR4 ligand SDF-1/CXCL12 also promotes tumor development by stimulating angiogenesis and by favoring metastasis of CXCR4-positive tumor cells to distant organs producing SDF-1/CXCL12. Furthermore, these angiogenic chemokines also directly enhance tumor cell survival and proliferation. In contrast, the CXCR3 ligands Mig/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11 are angiostatic and attract anti-tumoral T lymphocytes and may therefore mediate tumor growth retardation and regression. Thus, chemokines exert diverging, sometimes dual roles in tumor biology as described for esophageal and gastric cancer. Therefore extensive research is needed to completely unravel the complex chemokine code in specific cancers. Possibly, chemokine-targeted cancer therapy will have to be adapted to the individual's chemokine profile. PMID- 22079532 TI - Interplay between mutational and horizontally acquired resistance mechanisms and its association with carbapenem resistance amongst extensively drug-resistant Pseudomonas aeruginosa (XDR-PA). AB - Between 2003 and 2009, the prevalence of extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) increased significantly in northern Taiwan from 1.0% to 2.1%. Molecular methods were used to investigate the genetic relatedness and carbapenem resistance mechanisms of a collection of 203 non-repetitive XDR-PA isolates available for study. Using pulsed-field gel electrophoresis (PFGE), 52 genotypes were observed; one predominant genotype (pulsotype 1) was found in 57.6% of the isolates. Polymerase chain reaction (PCR), sequencing and quantitative reverse transcriptase PCR analyses demonstrated that one horizontally acquired mechanism [metallo-beta-lactamase (MBL) genes] and two mutational mechanisms (efflux and porins) accounted for the carbapenem resistance. The most predominant horizontally acquired mechanism was carriage of bla(VIM-3), which was found in 61.1% of isolates. Decreased expression of oprD was the most prevalent mutational mechanism and was found in 70.0% of the XDR-PA isolates, whereas overexpression of mexA was found in 27.6% of the isolates. The highlight of this study was the discovery of statistically significant relationships between certain horizontally acquired and mutational resistance mechanisms and their contribution to carbapenem susceptibility. MBL-producers expressed significantly lower MexAB and higher OprD than non-MBL-producers. Amongst isolates without an acquired beta lactamase gene, oprD expression was significantly reduced, whilst expression of efflux pumps was increased. Reduced OprD expression alone or the production of VIM-type MBLs showed similar contributions to a low to intermediate MIC(50) (minimum inhibitory concentration for 50% of the organisms) for carbapenems. Isolates with reduced OprD expression that simultaneously harboured bla(VIM) exhibited high levels of resistance to carbapenems, which implied that these two mechanisms had a synergistic effect on the MICs. PMID- 22079534 TI - Effect of antibiotic prescribing in primary care on meticillin-resistant Staphylococcus aureus carriage in community-resident adults: a controlled observational study. AB - The objectives of this study were to investigate the relationship between primary care antibiotics prescribed within 2 months and 12 months and the carriage of meticillin-resistant Staphylococcus aureus (MRSA) in nasal flora from a large representative sample of community-resident adults. S. aureus isolates were obtained from nasal samples submitted by UK resident adults aged >= 16 years registered with 12 general practices in the former Avon and Gloucestershire health authority areas. Individual-level antibiotic exposure data during the 12 months prior to providing the samples were collected from the primary care electronic records. MRSA status was determined by measuring resistance to cefoxitin. In total, 6937 adults were invited to take part, of whom 5917 returned a nasal sample. S. aureus was identified in 946 samples and a total of 761 participants consented to primary care record review and had complete data for the analyses. There was no evidence of an association between any antibiotic in the previous 2 months and MRSA isolation, with an adjusted odds ratio (aOR) of 1.33 [95% confidence interval (CI) 0.12-15; P=0.8]. There was a suggestion of an association between any antibiotic use in the previous 12 months and MRSA, with an aOR of 2.45 (95% CI 0.95-6.3; P=0.06). In conclusion, there is a suggestion that antibiotics prescribed within 12 months is associated with the carriage of MRSA, but not within 2 months, although the 2-month analysis had fewer data subjects and was therefore underpowered to detect this association. A larger study would be able to clarify these associations further. PMID- 22079533 TI - An antibacterial from Hypericum acmosepalum inhibits ATP-dependent MurE ligase from Mycobacterium tuberculosis. AB - In a project to characterise new antibacterial chemotypes from plants, hyperenone A and hypercalin B were isolated from the hexane and chloroform extracts of the aerial parts of Hypericum acmosepalum. The structures of both compounds were characterised by extensive one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and were confirmed by mass spectrometry. Hyperenone A and hypercalin B exhibited antibacterial activity against multidrug-resistant strains of Staphylococcus aureus, with minimum inhibition concentration ranges of 2-128 mg/L and 0.5-128 mg/L, respectively. Hyperenone A also showed growth-inhibitory activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG at 75 mg/L and 100mg/L. Neither hyperenone A nor hypercalin B inhibited the growth of Escherichia coli and both were non-toxic to cultured mammalian macrophage cells. Both compounds were tested for their ability to inhibit the ATP-dependent MurE ligase of M. tuberculosis, a crucial enzyme in the cytoplasmic steps of peptidoglycan biosynthesis. Hyperenone A inhibited MurE selectively, whereas hypercalin B did not have any effect on enzyme activity. PMID- 22079535 TI - Antibiotic resistance and an in vitro biofilm model. PMID- 22079536 TI - Demonstration of the use of the ICF framework in detailing complex functional deficits after major burn. AB - Burns can result in long term impairments, activity limitations and participation restrictions in a patients' life. The focus of current surgeries and therapy is to improve body functions and structures. However, often this does not translate to an improvement in activity and participation for the patient. Improvement in activity and participation is the ultimate goal of all therapy to enhance patient's quality of life. The incorporation of assessment measures at all levels of the International Classification of Functioning, Disability and Health (ICF) can assist in a holistic, patient centred approach to identify the complex impairments that impact on activity and participation, with a view to appropriately targeting future therapeutic interventions. This paper presents an example case of how implementing measures at all levels of the ICF can improve our understanding of a patient's body functions and structures, activity and participation. A number of the outcome measures utilised in this study are novel in the burns population, such that video footage supplements the methodology where relevant. PMID- 22079537 TI - Epidemiology and mortality of burned patients treated in the University Hospital Center in Tirana, Albania: an analysis of 2337 cases during the period 1998-2008. AB - BACKGROUND: The basis for qualitative changes concerning everyday clinical practice are created from epidemiological studies, which not only generalize situations but at the same time provide specific details of the country's features; especially during periods of social transition. The aim of this study was to present demographic and epidemiological features of severe burns treated in the Service of Burns in UHC (University Hospital Center) in Albania and to analyze burn mortality as an important outcome measure. METHOD: The data used was obtained by the analysis of the medical records of 2337 patients hospitalized in Burns Service ICU near in Tirana, Albania during 1998-2008. Statistical analysis is done with SPSS 15 software. Descriptive analyses, inferential statistics and Chi-square test and Kendall's tau_b are calculated. Logistic regression is used for the prediction of death probability by two risk variables, BSA burned and age. RESULTS: The severe burn incidence was 7 patients per 100,000 persons/year. The overall mean estimated BSA (%) is 22.8+/-14.7. The main causes of the burn were found to be the scalds in 61.8% of the cases followed by flame (23%), chemicals (10.7%) and electrical injury in 4.5% of the cases. The mean hospital period is 11.6+/-10. The overall mortality is 10.5%. Based on probability of death, we noticed that older age and larger burn size were associated with a higher likelihood of mortality. CONCLUSIONS: The long-term studies and the comparison of our results with the ones of other burn centers has allowed us to determine the actual level of care and as well as to build up contemporary protocols in order to improve the treatment with the objection of decreasing the mortality. PMID- 22079538 TI - Characterisation of the cell suspension harvested from the dermal epidermal junction using a ReCell(r) kit. AB - BACKGROUND: The use of non-cultured autologous cells to promote wound healing and in reconstructive procedures is increasing. One common method for preparing these cells is the use of the ReCell((r)) device. However, despite its current clinical use, no characterisation of the cell suspension produced using a ReCell((r)) device has been published. OBJECTIVE: To characterise the ReCell suspension that is applied to wounds for cell type, viability, yield, stability and proliferative potential. METHODS: The ReCell((r)) device was used to harvest cells from a 2 cm(2) piece of split-thickness skin isolated using a dermatome. The resulting cell suspension was analysed for cell yield, cell type, viability over time, proliferative potential and reproducibility. RESULTS: Average viable cell yield was 1.7*10(6)/cm(2) of tissue, with 75.5% of the total cell isolate viable. Total viable cell number was not significantly reduced after 4 h storage at 22 degrees C or 4 degrees C, and was stable for 24 h at 4 degrees C. Proliferative potential was assessed using a colony forming assay, with 0.3% of viable cells isolated forming keratinocyte colonies. Predominantly the suspension contained keratinocytes (64.3+/-28.8%) and fibroblasts (30.3+/-14.0%), with a small population of melanocytes also identified (3.5+/-0.5%). Finally, the supernatant contained low total protein (0.92 mg/ml) and the supernatant had no significant effects on cell viability or growth when applied ex vivo. CONCLUSIONS: These results suggest the ReCell((r)) device provides a method for the preparation of a cell suspension with high viability and proliferative potential, containing viable melanocytes and no apparent toxic cell debris. Further work on the sustained viability of these cells in vivo, and in particular after application to the wound, will be important to better understand the potential of the ReCell((r)) device in the clinic. PMID- 22079539 TI - Effect of Poloxamer 188 on deepening of deep second-degree burn wounds in the early stage. AB - OBJECTIVE: To discuss the effect of Poloxamer 188 (P188) on deepening of deep second-degree burn wounds in the early stage after burn. METHODS: We divided Wistar rats with deep second-degree burn wounds on the backs thereof into two groups, then intravenously injected P188 for the treatment group and intravenously injecting physiological saline for the control group, detecting the activity of Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase), myeloperoxidase (MPO) and the content of malonaldehyde (MDA) and succinic dehydrogenase (SDH) in the burn wound, and showing the degree of necrosis in the wound by haematoxylin-eosin (HE) and proliferating cell nuclear antigen (PCNA) immunohistochemical staining. RESULTS: In the control group and treatment group, the activity of SDH and Na(+)-K(+)-ATPase dropped to the lowest point 24 h after the burn took place, and then increased gradually, but was still far lower than the normal level at the furthest time point. At 24 h after burn, activity of SDH and Na(+)-K(+)-ATPase in the treatment group was higher than that of the control group (P<0.05); the activity of MPO of the control group reached the highest point at 24 h while that of MPO of the treatment group reached the highest point after 48 h; later, that of MPO of both groups decreased, but was still higher than the normal level. Compared with the highest values of the activity of MPO of both groups, that of the control group was higher than that of the treatment group (p<0.05); the contents of MDA of both groups kept increasing after the burn; 72 h later, that of the control group was higher than that of the treatment group (p<0.05). HE and PCNA staining showed progressive damage of the wound in the treatment group, which was decreased with treatment, particularly at the early stages. CONCLUSION: Systemic application of P188 on deep second-degree burn wounds at the early stage may alleviate wound deepening, whose mechanism may be related to timely sealing up the damaged cell membrane and inhibiting the inflammatory reaction. PMID- 22079540 TI - Analysis of IL-6, IL-10 and IL-17 genetic polymorphisms as risk factors for sepsis development in burned patients. AB - Infection risk, sepsis and mortality after severe burn are primarily determined by patient age, burn size, and depth. Whether genetic differences contribute to otherwise unexpected variability in outcomes is unknown. We sought to determine whether there was an association between IL-6, IL-10 and IL-17 polymorphisms with cytokine production and development of sepsis. We evaluated 71 patients with burns >=15% TBSA and 109 healthy subjects. The genotypes of IL-6 (-174C/G), IL-10 (-819C/T and -1082A/G) and IL-17 (7488T/C) polymorphisms were identified applying polymerase chain reaction protocols. The cytokine levels in serum were determined with enzyme-linked immunoabsorbent assays. Our results demonstrated no significant differences in the genotype frequencies studied between burn patients and healthy subjects. No significant associations were found among IL-6 and IL 17F genotypes and the related cytokine serum levels. Only IL-10 promoter -1082GG genotype was related to an increased IL-10 production in burned patients. In addition, septic subjects bearing -1082G/G genotype have shown the highest and non-septic bearing -1082A/* genotypes the lowest IL-10 serum levels. All together these data seem to indicate that genetically determined individual difference in IL-10 production might influence the susceptibility to septic complications in burned patients and suggest that these markers might be useful in burned patient management. PMID- 22079541 TI - The protective role of ascorbic acid in burn-induced testicular damage in rats. AB - OBJECTIVE: To investigate the ability of ascorbic acid to protect the testes from damage in severe burns. DESIGN: Experimental study. SETTING: University of Lagos Medical School, Department of Anatomy. ANIMALS: 28 adult male Wistar rats (250 300 g). INTERVENTION: Third degree burn was induced on 40% body surface area of rats and they were given ascorbic acid at 4 mg/kg over 8 weeks. MAIN OUTCOME MEASURED: Weight of reproductive organs and epididymal sperm parameters were measured. Oxidative status was assayed and a semi-quantitative assessment of histologic changes was also carried out. RESULTS: Burn caused severe seminiferous tubular damage, especially germ cell loss (p<0.05). This was matched by significant reduction in sperm density and morphology (p<0.05). Burn also increased oxidative stress, with elevated malondialdehyde (MDA) levels (p<0.01) and changes in catalase and superoxide dismutase enzyme levels. Ascorbic acid prevented the changes in all sperm parameters. It normalized MDA levels (p<0.01) and attenuated changes in the levels of catalase and superoxide dismutase. Ascorbic acid treatment also significantly reduced histologic damage to seminiferous tubules. CONCLUSION: This study shows that severe thermal injury causes significant testicular damage and impairs spermatogenesis. It also shows that ascorbic acid protects the testis from such damage and therefore has the potential to be a useful adjunct therapy during treatment of young males with severe burns. PMID- 22079542 TI - Effects of Ligustrazine on pancreatic and renal damage after scald injury. AB - Organ protection is a routine therapeutic application to severe burn/scald injuries, and organic damage following early scald injury is not absolutely elucidated. Our aim is to verify the good effects of Ligustrazine on pancreatic and renal damage associated with early scald injury. A total of 120 Lewis rats subjected to 30% total body surface area (TBSA) scald injury, were randomly divided into simple scald group (S group) and Ligustrazine treated group (L group). Both pancreatic and renal malondialdehyde (MDA) level and superoxide dismutase (SOD) were determined. Serum amylase, serum creatinine (Scr) and blood urea nitrogen (BUN) were identified as well as examining the kidneys histologically with Immunohistochemistry (IHC) for major histocompatability complex class I chain-related antigen A (MICA) and Bcl-2 at 0, 1, 6, 12, 18, 24, 48 and 72 h after scald. Ligustrazine decreased MDA levels and ameliorated the downregulation of SOD activity. MICA was up-regulated after scald, and the up regulation could be greatly diminished by Ligustrazine. Bcl-2 was up-regulated after scald, especially in the L group. From 24 to 72 h, in comparison with the L group, higher levels of BUN, Scr and serum amylase were observered in the S group, which were also higher than the common upper limits. Therefore, our results demonstrated potential pancreatic and renal damage associated with autoimmunity and oxidant attack occurred following early scald injury. Ligustrazine exhibits significant protective effects. PMID- 22079543 TI - Burn patients' experience of pain management: a qualitative study. AB - Pain is a major problem after burns and researchers continue to report that pain from burns remains undertreated. The inadequate pain control results in adverse sequalae physically and psychologically in the burn victims. A better understanding of a burn patient's experience is important in identifying the factors responsible for undertreated pain and establishing effective pain management guidelines or recommendation in the practice of pain relief for burn injuries. This study sought to explore and describe the experience that patients have about pain related to burn-injury during hospitalization. Semi-structured interviews were conducted on eight patients with moderate to severe pain from burn injuries recruited from a Burn Centre in Northwest China. Data was collected by in-depth interviews and qualitative description after full transcription of each interview. Analysis involved the identification of themes and the development of a taxonomy of patients' experience of burn pain and its management. Three themes were indentified: (1) patients' experience of pain control, (2) patients' perception on burn pain management, and (3) patients' expectation of burn pain management. Findings from this study suggested that patients experience uncontrolled pain both physically and psychologically which may serve as an alert for awareness of health professionals to recognize and establish a multidisciplinary pain management team for burn victims, including surgeons, critical care specialists, anesthesiologists, nurses, psychologists, and social workers to accomplish safe and effective strategies for pain control to reach an optimal level of pain management in burn patients. It also provides insights and suggestions for future research directions to address this significant clinical problem. PMID- 22079545 TI - Identification and functional characterization of indole-3-acetamide-mediated IAA biosynthesis in plant-associated Fusarium species. AB - The plant hormone indole-3-acetic acid (IAA) can be synthesized from tryptophan via the intermediate indole-3-acetamide (IAM). The two genes, IaaM (encoding tryptophan monooxygenase) and IaaH (encoding indole-3-acetamide hydrolase) that constitute the IAM pathway have been described in plant-associated bacteria. We have identified putative homologs of the bacterial IaaM and IaaH genes in four Fusarium species -Fusarium proliferatum, Fusarium verticillioides, Fusarium fujikuroi, and Fusarium oxysporum. In all four species the two genes are organized next to each other in a head to head orientation and are separated by a short non-coding region. However, the pathway is fully functional only in the orchid endophytic strain F. proliferatum ET1, which produces significant amounts of IAM and IAA. Minor amounts of IAM are produced by the corn pathogen F. verticillioides strain 149, while in the two other species, the rice pathogen F. fujikuroi strain m567 and the tomato pathogen F. oxysporum f. sp. lycopersici strain 42-87 the IAM pathway is inactive. Deletion of the entire gene locus in F. proliferatum ET1 resulted in drastic reduction of IAA production. Conversely, transgenic strains of F. fujikuroi over-expressing the F. proliferatum IAM genes produced elevated levels of both IAM and IAA. Analysis of the intergenic promoter region in F. proliferatum showed that transcriptional activation in direction of the IaaH gene is about 3-fold stronger than in direction of the IaaM gene. The regulation of the IAM genes and the limiting factors of IAA production via the IAM pathway are discussed. PMID- 22079546 TI - Prevalence of specific and phylogenetically closely related genotypes in the population of Candida albicans associated with genital candidiasis in China. AB - Genitourinary candidiasis, which is most frequently caused by Candida albicans, is a common problem worldwide. The pathogenesis of the infection, especially recurrence of the infection, remains to be elucidated. This study analyzed 199 independent Chinese C. albicans isolates using multilocus sequence typing (MLST) and microsatellite typing, with the focus on the isolates associated with vulvovaginal candidiasis (VVC) of Chinese women. MLST data of 221 vaginal isolates from other countries available from the consensus MLST database of C. albicans were retrieved for comparison. A total of 124 diploid sequence types (DSTs) were recognized from the Chinese C. albicans isolates, among which, 98 (79.0%) have not been reported in the MLST database of the species. The majority of the VVC (71.6%) and balanitis (92.3%) isolates from China were located in clade 1 of C. albicans; while only 40.6% of the vaginal isolates and 7.8% of the oral isolates from healthy volunteers were found in the same clade. Furthermore, 69.1% of the VVC and 84.5% of the balanitis isolates concentrated in a cluster of clade 1 with DST 79 as the primary founder. The isolates in this cluster possessed microsatellite genotypes CAI 30-45, CAI 32-46 and their close derivatives. Interestingly, a remarkable difference in genotype distribution patterns between Chinese and non-Chinese vaginal isolates of C. albicans was observed. Only 11.3% of the non-Chinese vaginal isolates compared were located in the cluster concentrated with Chinese VVC isolates. The results suggest significant association of specific and genetically similar genotypes with genital infections in China. PMID- 22079548 TI - Proteins: histones and chromatin. PMID- 22079544 TI - Update on Wnt signaling in bone cell biology and bone disease. AB - For more than a decade, Wnt signaling pathways have been the focus of intense research activity in bone biology laboratories because of their importance in skeletal development, bone mass maintenance, and therapeutic potential for regenerative medicine. It is evident that even subtle alterations in the intensity, amplitude, location, and duration of Wnt signaling pathways affects skeletal development, as well as bone remodeling, regeneration, and repair during a lifespan. Here we review recent advances and discrepancies in how Wnt/Lrp5 signaling regulates osteoblasts and osteocytes, introduce new players in Wnt signaling pathways that have important roles in bone development, discuss emerging areas such as the role of Wnt signaling in osteoclastogenesis, and summarize progress made in translating basic studies to clinical therapeutics and diagnostics centered around inhibiting Wnt pathway antagonists, such as sclerostin, Dkk1 and Sfrp1. Emphasis is placed on the plethora of genetic studies in mouse models and genome wide association studies that reveal the requirement for and crucial roles of Wnt pathway components during skeletal development and disease. PMID- 22079549 TI - Age-related changes in endothelial function and blood flow regulation. AB - Vascular endothelial dysfunction is regarded as a primary phenotypic expression of normal human aging. This senescence-induced disorder is the likely culprit underlying the increased cardiovascular and metabolic disease risks associated with aging. The rate of this age-dependent deterioration is largely influenced by the poor-quality lifestyle choice, such as smoking, sedentary daily life, chronic alcohol ingestion, high salt intake, unbalanced diet, and mental stress; and it is accelerated by cardiovascular and metabolic diseases. Although minimizing these detrimental factors is the best course of action, nonetheless chronological age steadily impairs endothelial function through reduced endothelial nitric oxide synthase (eNOS) expression/action, accelerated nitric oxide (NO) degradation, increased phosphodiesterase activity, inhibition of NOS activity by endogenous NOS inhibitors, increased production of reactive oxygen species, inflammatory reactions, decreased endothelial progenitor cell number and function, and impaired telomerase activity or telomere shortening. Endothelial dysfunction in regional vasculatures results in cerebral hypoperfusion triggering cognitive dysfunction and Alzheimer's disease, coronary artery insufficiency, penile erectile dysfunction, and circulatory failures in other organs and tissues. Possible prophylactic measures to minimize age-related endothelial dysfunction are also summarized in this review. PMID- 22079550 TI - Species identification in the taxonomically neglected, highly diverse, neotropical parasitoid wasp genus Notiospathius (Braconidae: Doryctinae) based on an integrative molecular and morphological approach. AB - Various DNA sequence-based methods for species delineation have recently been developed to assess the species-richness of highly diverse, neglected invertebrate taxa. These methods, however, need to be tested under a variety of conditions, including the use of different markers and parameters. Here, we explored the species diversity of a species-rich group of braconid parasitoid wasps, the Neotropical genus Notiospathius, including 233 specimens from 10 different countries. We examined sequences of two mitochondrial (mt) (COI, cyt b) and one nuclear (wg) gene fragments. We analysed them separately as well as concatenating the mt data with the general mixed Yule-coalescent (GMYC) model for species delineation using different tree-building methods and parameters for reconstructing ultrametric trees. We evaluated the performance of GMYC analyses by comparing their species delineations with our morphospecies identifications. Reconstructing ultrametric trees with a relaxed lognormal clock rate using the program BEAST gave the most congruent results with morphology for the two mt markers. A tree obtained with wg using the programs MrBayes+Pathd8 had the fewest cases of incongruence with morphology, though the performance of this nuclear marker was considerably lower than that of COI and cyt b. Species delimitation using the coalescent prior to obtain ultrametric trees was morphologically more congruent with COI, whereas the Yule prior was more congruent with cyt b. The analyses concatenating the mt datasets failed to recover some species supported both by morphology and the separate analyses of the mt markers. The highest morphological congruence was obtained with the GMYC analysis on an ultrametric tree reconstructed with cyt b using the relaxed lognormal clock rate and the Yule prior, thus supporting the importance of using alternative markers when the information of the barcoding locus (COI) is not concordant with morphological evidence. Seventy-one species were delimited based on the congruence found among COI, cyt b and morphology. Both mt markers also revealed the existence of seven potential cryptic species. This high species richness from a scattered geographical sampling indicates that there is a remarkable number of Notiospathius species that remains undiscovered. PMID- 22079551 TI - Phylogenetic and functional analyses of the cytochrome P450 family 4. AB - Cytochrome P450 family 4 (CYP4) proteins metabolize fatty acids, eicosanoids, and vitamin D and are important for chemical defense. The purpose of this study was to determine the evolutionary relationships between vertebrate CYP4 subfamilies and raise functional hypotheses regarding CYP4 subfamilies with little empirical data. 132 CYP4 sequences from 28 species were utilized for phylogenetic reconstructions by maximum likelihood and Bayesian inference. Monophyly was not found with the CYP4T and CYP4B subfamilies. CYP4V clustered with invertebrate subfamilies. Evolutionary rates of functional divergence were high in pairwise comparison with CYP4X yet, comparisons with mammalian CYP4F22 genes generally had no statistically significant divergence. Radical biochemical changes were detected in regions associated with substrate binding and the active site in comparisons among the CYP4A, CYP4X, and CYP4B subfamilies. Lastly, gene expression patterns, determined in silico with EST libraries from human, chicken, frog and fish, for CYP4V was markedly different between human and actinopterygian species. Further consideration should be given to the nomenclature of the CYP4T and CYP4B subfamily genes. Strong support was seen for the placement of CYP4A as a basal subfamily to CYP4X and CYP4Z. The B, B', J', K', K" helices and a region at the end of C-terminus were suggested as conserved regions in CYP4 genes. The function of CYP4X was hypothesized to specialize in metabolism of long chain fatty acids. CYP4F22 genes may share a similar function to other CYP4F genes, although gene expression sites were different. PMID- 22079552 TI - Molecular phylogeny of hipposiderid bats from Southeast Asia and evidence of cryptic diversity. AB - Old World leaf-nosed bats (Hipposideridae) are among the most widespread and ecologically diverse groups of insectivorous bats in the Old World tropics. However, phylogenetic relationships in Hipposideridae are poorly resolved at both the generic and species levels, and deep genetic divergence within several Southeast Asian species suggests that current taxonomy underestimates hipposiderid diversity in this region. We used mitochondrial and nuclear sequence data to conduct the first extensive molecular phylogenetic analysis of Southeast Asian hipposiderid bats. Inclusion of multiple samples per taxon allowed testing for evidence of evolutionarily distinct lineages within taxa currently defined as single species. In contrast to earlier phylogenies based on morphometrics, molecular data support monophyly of Hipposideros, but are ambiguous regarding the monophyly of Hipposideridae. With a few exceptions, molecular data also support currently recognized species groups classified by qualitative morphological characters. Widespread paraphyly and polyphyly within many currently recognized species of Hipposideros indicates that evolutionary diversity in the genus is underrepresented by current nomenclature. Comparison of available morphological and echolocation data suggest that both geographic isolation and ecological selection have contributed to the diversification of Southeast Asian hipposiderid bats. PMID- 22079553 TI - Failure to eradicate the lungworm Dictyocaulus viviparus on dairy farms by a single mass-treatment before turnout. AB - On two dairy farms it was attempted to eradicate lungworm, Dictyocaulus viviparus, by means of a single mass-treatment of all cattle that had been grazed the previous year(s), before turnout in the spring. Both farms experienced two years of lungworm outbreaks in the adult dairy herd prior to this study. Following confirmation that both herds contained lungworm carriers, all animals older than approximately 6 months were treated with eprinomectin in March 2007. One week after treatment none of the animals were shedding lungworm larvae. Subsequently, animals were pastured according to normal farm routine. From August to November all first-calving heifers were coprologically and serologically monitored for lungworm infection. During 2007 both farms remained lungworm negative and did not report any clinical sign indicative for a lungworm infection. The following year, on one of the farms replacements grazing on cow pastures, started showing signs of parasitic bronchitis which was serologically confirmed. The other herd remained free of parasitic bronchitis until at least the fourth year after the mass treatment, although some coughing was noticed in 2008 among first-lactation heifers. It was concluded that a single mass-treatment before the grazing season may be useful to break a series of annual lungworm outbreaks. However, it is not a secure method to prevent parasitic bronchitis for more than one year. PMID- 22079554 TI - Racial differences in sudden cardiac death among hypertensive patients during antihypertensive therapy: the LIFE study. AB - BACKGROUND: In the general population, blacks appear to have a higher risk of sudden cardiac death (SCD). OBJECTIVES: To determine whether black hypertensive patients have a higher SCD incidence. METHODS: The incidence of SCD was examined in 533 black and 8660 nonblack hypertensive patients with electrocardiographic left ventricular hypertrophy randomly assigned to losartan- or atenolol-based treatment. RESULTS: During a mean follow-up of 4.8 +/- 0.9 years, SCD occurred in 178 patients (1.9%); 5-year SCD incidence was significantly higher in black than in nonblack patients (3.9% vs 1.9%; P = .007). In univariate Cox analyses, black patients had a 97% higher risk of SCD (hazard ratio 1.97; 95% confidence interval 1.19-3.25; P = .015). In multivariate Cox analyses adjusting for randomized treatment, age, sex, body mass index, diabetes, history of heart failure, atrial fibrillation, myocardial infarction, ischemic heart disease, stroke, peripheral vascular disease, smoking, serum total and high-density lipoprotein cholesterol level, creatinine level, glucose level, and urine albumin/creatinine ratio and for incident myocardial infarction, in-treatment heart rate, QRS duration, diastolic and systolic pressure, Cornell voltage-duration product, and Sokolow Lyon voltage left ventricular hypertrophy treated as time-varying covariates, black race remained associated with a 98% increased risk of SCD (hazard ratio 1.98; 95% confidence interval 1.12-3.59; P = .020). CONCLUSIONS: Black hypertensive patients are at increased risk of SCD. The higher risk of SCD in black patients persists after adjusting for the higher prevalence of risk factors in black patients, in-treatment blood pressure, and the established predictive value of in-treatment electrocardiographic left ventricular hypertrophy and heart rate for SCD in this population. PMID- 22079555 TI - Antitachycardia pacing or shock therapy-trick or treat? PMID- 22079556 TI - Shock-induced focal arrhythmias: not driven by calcium? PMID- 22079557 TI - Prospective evaluation of electrocardiographic parameters in cardiac resynchronization therapy: detecting nonresponders by left ventricular pacing. AB - BACKGROUND AND OBJECTIVE: The purpose of this prospective evaluation of electrocardiographic (ECG) parameters was to identify predictive parameters for cardiac resynchronization therapy (CRT) response. METHODS: One hundred two patients undergoing first CRT implantation were evaluated prospectively. Symptomatic response was defined as improvement in New York Heart Association functional class of at least 1 class within 3-month follow-up. Twelve-lead ECG of the intrinsic rhythm during biventricular (BIV), right ventricular (RV), and left ventricular (LV) pacing was obtained and analyzed in terms of QRS width and QRS axis (Datinf Measure Software, Datinf GmbH, Tubingen, Germany). In total, 77.5% (n = 79) of patients fulfilled the predefined clinical criterion for response. Patients with dilated cardiomyopathy were more likely to respond to CRT than were patients with ischemic cardiomyopathy (85% vs 71.8%, P = .034). A shorter QRS duration during LV pacing and, in particular, a shorter LV paced than RV paced QRS width were strong and independent predictors for response (-20.13 +/- 33.2 ms in responders vs 6.05 +/- 27.3 ms in nonresponders, P = .001). No statistically significant differences were found in RV and BIV paced QRS width or in QRS axis (P >.5). CONCLUSION: This study describes novel and easily obtainable ECG measurements that can be performed during LV lead positioning to optimize clinical outcome of CRT in heart failure patients. PMID- 22079558 TI - Full report from the first annual Heart Rhythm Society Research Forum: a vision for our research future, "dream, discover, develop, deliver". PMID- 22079559 TI - Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen. AB - Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO(2) could be used to optimize the outcome of oxygen dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO(2) during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO(2) by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO(2) at more than one site in the glioma and contralateral cerebral tissue. The pO(2) of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO(2) of 27-36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO(2) of 7-12mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO(2) was investigated in rats breathing 100% O(2). A significant increase in F98 tumor and contralateral brain pO(2) was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO(2). This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO(2). PMID- 22079560 TI - [New insights in oncology: epigenetics and cancer stem cells]. AB - Cancer is a multi-etiologic, multistage disease with a prevalent genetic component, which happens when a large number of genes, critical for cell growth, death, differentiation, migration, and metabolic plasticity are altered irreversibly, so as to either "gain" (oncogenes) or "lose" (tumour suppressors) their function. Recent discoveries have revealed the previously underestimated etiologic importance of multiple epigenetic, that is to say, reversible factors (histone modifications, DNA methylation, non-coding RNA) involved in the transcriptional and post-transcriptional regulation of proteins, indispensable for the control of cancerous phenotype. Stable alterations of epigenetic machinery ("epimutations") turn out to play a critical role at different steps of carcinogenesis. In addition, due to substantial recent progress in stem cell biology, the new concept of cancer stem cells has emerged. This, along with newly discovered epigenetic cancer mechanisms, gives rise to a hope to overcome radio- and chemo-resistance and to eradicate otherwise incurable neoplasms. PMID- 22079561 TI - tPA in the injured central nervous system: different scenarios starring the same actor? AB - When in 1947, Astrup and Permin reported that animal tissues contain fibrinokinase, a plasminogen activator, and when Pennica and colleagues (Pennica et al., 1983) cloned and expressed human tissue plasminogen activator (tPA) in Escherichia coli in 1983, they might did not realize how much their pioneer work would impact the life of millions of patients suffering from myocardial infarction or ischemic stroke. Some years after, accumulating evidence shows that tPA is not just a plasminogen activator of endothelial origin. Indeed, the main function of tPA released from the endothelium is to convert fibrin-bound plasminogen into active plasmin, thus dissolving the fibrin meshwork of blood clots. But this serine protease is also expressed by several cell types, and its beneficial and deleterious actions stand beyond fibrinolysis or even proteolysis. We will review here the reported effects and mechanisms of action of tPA in the course of three different pathologies of the central nervous system (CNS): spinal cord injury, ischemic stroke and multiple sclerosis. While these three disorders have distinct aetiologies, they share some pathogenic mechanisms. We will depict the main "good" and "bad" sides of tPA described to date during each of these pathological situations, as well as the proposed mechanisms explaining these effects. We speculate that due to common pathogenic pathways, tPA's actions described in one particular disease could in fact occur in the others. Finally, we will evaluate if tPA could be a therapeutic target for these pathologies. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22079562 TI - Determinants of neurologic deterioration and stroke-free survival after spontaneous cervicocranial dissections: a multicenter study. AB - Patients with spontaneous cervicocranial dissection (SCCD) may experience new or recurrent ischemic events despite antiplatelet or anticoagulant therapy. Treatment with stent placement is an available option; however, the literature on patient selection is limited. Thus, identifying patients at high risk for neurologic deterioration after SCCD is of critical importance. The present study examined the rate of neurologic deterioration in medically treated patients with SCCD and evaluated demographic, clinical, and radiologic factors affecting this deterioration. We retrospectively identified consecutive patients with SCCD over a 7-year period from 3 medical institutions, and evaluated the relationships between demographic data, clinical characteristics, and angiographical findings and subsequent neurologic outcomes. Neurologic deterioration was defined as transient ischemic attack (TIA), ischemic stroke, or death occurring during hospitalization or within 1 year of diagnosis. Kaplan-Meier curves were used to determine neurologic event-free survival up to 12 months. A total of 69 patients (mean age, 47.8 +/- 14 years; 45 males) with SCCD were included in the study. Eleven patients (16%) experienced in-hospital neurologic deterioration (TIA in 9, ischemic stroke in 1) or death (1 patient). An additional 8 patients developed neurologic deterioration within 1 year after discharge (TIA in 5, ischemic stroke in 2, and death in 1). The overall 1-year event-free survival rate was 72%. Women (P = .046), patients with involvement of both vertebral arteries (P = .02), and those with intracranial arterial involvement (P = .018) had significantly higher rates of neurologic deterioration. Our findings indicate that neurologic deterioration is relatively common after SCCD despite medical treatment in women, patients with bilateral vertebral artery involvement, and those with intracranial vessel involvement. PMID- 22079563 TI - Inhibition of hypoxia-induced [(3)H]glycine release from chicken retina by the glycine transporter type-1 (GlyT-1) inhibitors NFPS and Org-24461. AB - Chicken posterior eyecup lined by the retina were prepared, loaded with [(3)H]glycine and superfused in order to determine its release in various experimental conditions. Electrical field stimulation of the retina evoked [(3)H]glycine release with a voltage- and frequency-dependent manner and this release may be originated from glycinergic amacrine cell processes of the inner plexiform layer of the retina. Glycine released from an abundance of different amacrine cells may modulate retinal circuitry by activation of inhibitory glycine receptors and by acting as a coagonist on N-methyl-d-aspartate receptors on AII amacrine cells and retinal ganglion cells. The latter effect of glycine may be modulated by glycine transporter type-1. Cells with glycine transporter type-1 immunopositive staining were visualized in the inner nuclear layer and dens immunolabeling was also detected throughout the inner plexiform layer of chicken retina. Glycine and the substrate-type glycine transporter type-1 inhibitor sarcosine increased [(3)H]glycine release from glycinergic amacrine cells and/or glial cells by extrusion of glycine from cytoplasmic pools by homo- and heteroexchange mechanisms. Deprivation of oxygen and glucose from the buffer used for superfusion evoked a marked increase in [(3)H]glycine efflux, an effect probably due to reverse mode operation of glycine transporter type-1. The non transportable glycine transporter type-1 inhibitors NFPS and Org-24461, which did not alter [(3)H]glycine efflux from isolated chicken retina by themselves in normoxic condition, inhibited oxygen and glucose deprivation-induced [(3)H]glycine release. It is concluded that reduction of the N-methyl-d-aspartate receptor coagonist glycine concentrations in hypoxic conditions by glycine transporter type-1 inhibitors may decrease N-methyl-d-aspartate receptor-mediated neuronal toxicity and cell death in retinal tissue. PMID- 22079564 TI - Characterization of daptomycin oligomerization with perylene excimer fluorescence: stoichiometric binding of phosphatidylglycerol triggers oligomer formation. AB - Daptomycin is a lipopeptide antibiotic that binds to and depolarizes bacterial cell membranes. Its antibacterial activity requires calcium and correlates with the content of phosphatidylglycerol in the target membrane. Daptomycin has been shown to form oligomers on liposome membranes. We here use perylene excimer fluorescence to further characterize the membrane-associated oligomer. To this end, the N-terminal fatty acyl chain was replaced with perylene-butanoic acid. The perylene derivative retains one third of the antibacterial activity of native daptomycin. On liposomes containing phosphatidylcholine and phosphatidylglycerol, as well as on Bacillus subtilis cells, the perylene-labeled daptomycin forms excimers, which shows that the N-terminal acyl chains of neighboring oligomer subunits are in immediate contact with one another. In a lipid bicelle system, oligomer formation can be titrated with stoichiometric amounts of phosphatidylglycerol. Therefore, the interaction of daptomycin with a single molecule of phosphatidylglycerol is sufficient to trigger daptomycin oligomerization. PMID- 22079565 TI - Comparison of sensory recovery at the subfascial and suprafascial donor sites of the free radial flap. AB - The radial flap may be raised using a subfascial or suprafascial approach. The latter donor site is associated with fewer healing complications. We retrospectively evaluated the quality of sensory recovery within two comparable groups of 30 patients with subfascial and suprafascial donor sites. When considering the two groups, two-point discrimination was the modality most commonly reduced, with 97% of patients in both groups having reduced sensation in at least one anatomical zone. Sensation of sharp touch was most often lost; 90% in the subfascial and 83% in the suprafascial groups lost sensation in at least one anatomical zone. Roughly half the patients had reduced perception of light touch (43% and 50%), whilst perception of heat (27% and 17%) and cold (33% and 27%) were lost least often. At least one modality in at least one anatomical zone was lost or reduced in all patients, and roughly two-thirds (73% and 63%) had a reduction in 3 or more. The only significant difference between the donor and non donor arms was reduced perception of sharp touch in the anterior forearm in both groups (p<0.001). Perception at the two sites (including the anatomical snuff box) was similar except for superior thenar palmar light touch (p=0.015) in the suprafascial group, which may indicate injury to the thenar cutaneous sensory branches during subfascial dissection. PMID- 22079566 TI - Distraction osteogenesis after irradiation in rabbit mandibles. AB - The aim of this study was to investigate the influence of irradiation on the formation of bone after distraction osteogenesis in rabbit mandibles. Sixteen rabbits were randomly divided into 3 groups: one was given 50Gy (n=6), one was given 60Gy (n=6), and one acted as a control group (n=4). One month after irradiation, the distractors were inserted. The control group was not irradiated. After a latency period of 8 days, distraction was activated at a rate of 0.4mm twice a day. The mandibles were harvested 6 weeks after consolidation. The specimens and histological examination showed good formation of bone. Histological slides stained with haematoxylin and eosin confirmed that the regeneration was bone. The bony trabeculae of the control group were much better than those of the irradiated groups. However, the nuclei of osteocytes were round and the osteoblasts around the trabeculae were columnar or cubic in shape in the irradiated groups. Osteoid was present in the dense fibrous connective tissue. There were significant differences in the surface:volume ratio of areas of bony trabeculae between the control and both experimental groups (p=0.010 and p=0.001), but there was no significant difference between the 50Gy and 60Gy groups. The results suggested that preoperative radiation prevented optimal regeneration of bone. However, the microscopic appearance of osteocytes and osteoblasts and the osteoid in the dense fibrous connective tissue in both irradiated groups showed that osteogenesis was still active and in progress. These findings may indicate that bone formation had only been delayed. The evidence was similar for both 50Gy and 60Gy. PMID- 22079567 TI - Evaluation of cyclooxygenase-2 expression in canine mast cell tumours. AB - Mast cell tumours (MCTs) are among the most common cutaneous neoplasms in dogs and have a highly variable clinical behaviour. Cyclooxygenase (Cox) catalyzes the rate-limiting step in prostanoid biosynthesis and has recently gained attention as a prognostic factor and therapeutic target in human and animal oncology. In order to evaluate the potential value of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of canine MCTs, expression of Cox-2 was determined in 49 such tumours (14 of grade I, nine of grade II and 22 of grade III). Cox-2 was expressed by 86% of the tumours studied. The percentage of labelled cells ranged from isolated positive cells throughout the tumour (n=8) to localized foci of labelled cells (n=3) or diffuse labelling of >50% of the cells (n=31). The intensity of Cox-2 labelling ranged from weak (n=4) to moderate (n=16) and strong (n=22) and was greatest at the advancing margin of the tumour. The intensity of Cox-2 labelling was significantly different between the three histological groups (P=0.018). However, no significant differences were noted for the percentage of Cox-2 positive cells (P=0.122) and for the immunoreactivity score (P=0.348) between the histological grades. The results of this study suggest that NSAIDs, particularly Cox-2 inhibitors, may be of value in the treatment of canine MCTs. PMID- 22079568 TI - StackTIS: a stacked generalization approach for effective prediction of translation initiation sites. AB - The prediction of the translation initiation site in an mRNA or cDNA sequence is an essential step in gene prediction and an open research problem in bioinformatics. Although recent approaches perform well, more effective and reliable methodologies are solicited. We developed an adaptable data mining method, called StackTIS, which is modular and consists of three prediction components that are combined into a meta-classification system, using stacked generalization, in a highly effective framework. We performed extensive experiments on sequences of two diverse eukaryotic organisms (Homo sapiens and Oryza sativa), indicating that StackTIS achieves statistically significant improvement in performance. PMID- 22079569 TI - Cyclin-dependent kinases 5 template: useful for virtual screening. AB - The present study reports the development of a template for the active binding site of Cdk5 for structure-based drug design. The developed template of Cdk5 was validated by redocking with ligands I (PBD code 1UNG), II (PBD code 1UNL) and III (PBD code 1UNH). The results demonstrate a good match of the docked and the crystallographic binding orientations with RMSD less than 2.0A. The validation results show that the constructed Cdk5 template is a good model system for predicting ligand binding orientations and binding affinities. Furthermore, the developed template was applied to predict binding mode and binding affinity of thirty-six known Cdk5 inhibitors. The results showed that the binding energy of almost Cdk5 inhibitors related to their biological evaluation. PMID- 22079570 TI - Clinical expectations: what facilitators expect from ESL students on clinical placement. AB - Many nursing students for whom English is a second language (ESL) face challenges related to communication on clinical placement and although clinical facilitators are not usually trained language assessors, they are often in a position of needing to assess ESL students' clinical language performance. Little is known, however, about the particular areas of clinical performance facilitators focus on when they are assessing ESL students. This paper discusses the results of a study of facilitators' written assessment comments about the clinical performance of a small group of ESL nursing students over a two and a half year period. These comments were documented on students' clinical assessment forms at the end of each placement. The results provide a more detailed insight into facilitators' expectations of students' language performance and the particular challenges faced by ESL students and indicate that facilitators have clear expectations of ESL students regarding communication, learning styles and professional demeanour. These findings may help both ESL students and their facilitators better prepare for clinical placement. PMID- 22079571 TI - Ultrastructural characterization of rat neurons in primary culture. AB - Few studies have addressed the ultrastructure and morphology of neurons in primary pure culture. We therefore use immunohistochemistry and electron microscopy to investigate the ultrastructure of cultured neurons during extended incubation in vitro. Rat cerebral cortex neurons were cultured in NeurobasalTM medium. Adherent cells developed as networks of single neurons or clusters depending on the plating density. Almost all surviving cells were neurons as demonstrated by neurofilament immunolabeling. The number of cultured neurons increased substantially to 14-21 days in vitro (DIV) and then plateaued and subsequently declined. From DIV 1-10 neurons extended large neurites, followed by the development of fine and dense neurites, and neurones survived until DIV 30 50. Notably, numerous mitochondria were observed along fibrous elements within neurites, suggestive of active intracellular trafficking. Electron microscopy also revealed that multiple types of synapses were formed between neurons. These ultrastructural results confirm previous reports of electrophysiological activity in cultured neurons. However many neurons contained distorted mitochondria and abnormal organelles including multilamellar vesicles and multivesicular myeloid bodies. The proportion of neurons containing abnormal organelles increased significantly in culture medium supplemented with antibiotics. On long-term culture neuronal death and apoptotic nuclei were observed. Despite the presence of abnormal organelles, the ultrastructure of cultured neurons was very similar to that of in vivo neurons; in vitro culture therefore provides a useful tool for studies on neuronal development, aging, and neurotransmission. PMID- 22079572 TI - Meta-analysis of microarray gene expression studies on intracranial aneurysms. AB - The rupture of intracranial aneurysms (IAs) is one of the most devastating neurological conditions known to date. Although treatment has changed dramatically throughout the last decades, the outcome of patients still has a poor prognosis. Besides environmental factors, genomics seem to be a very important factor in the genesis of this disease. Different approaches to decrypt genomic causes were pursued throughout the last years. Microarray gene expression studies comparing aneurysmal and healthy tissue seem to be one of the most promising approaches. However, large amounts of data created with each study, make a comparison or interpretation of results difficult. We analyzed microarray gene expression studies on IAs (vs. control tissue) and compared lists of genes with altered expression provided by the authors. Additionally functional pathway analysis was performed. We identified five microarray gene expression studies analyzing a total of 60 samples of IA tissue (30 ruptured IA, 30 unruptured IA). A total of 507 genes with altered expression were listed, of which 57 showed differences in more than two studies and seven in more than three studies (BCL2, COL1A2, COL3A1, COL5A2, CXCL12, TIMP4, TNC). The meta-analysis of five microarray gene expression studies on IAs revealed seven genes that are very likely to be involved in the genesis of IAs. Further analysis of these genes might provide valuable information on mechanisms causing this disease. PMID- 22079573 TI - Identification of neuroglobin-interacting proteins using yeast two-hybrid screening. AB - Neuroglobin (Ngb) is a globin protein that is highly and specifically expressed in brain neurons. A large volume of evidence has proven that Ngb is a neuroprotective molecule against hypoxic/ischemic brain injury and other related neurological disorder; however, the underlying mechanisms remain poorly understood. Aiming to provide more clues in understanding the molecular mechanisms of Ngb's neuroprotection, we performed yeast two-hybrid screening to search for proteins that interact with Ngb. From a mouse brain cDNA library, we found totally 36 proteins that potentially interact with Ngb, and 10 of them were each identified in multiple positive clones. The shared sequences within these multiple clones are more likely to be Ngb-interacting domains. In primary cultured mouse cortical neurons, immuno-precipitation was performed to confirm the interactions of selected proteins with Ngb. The discovered Ngb-interacting proteins in this study include those involved in energy metabolism, mitochondria function, and signaling pathways for cell survival and proliferation. Our findings provide molecular targets for investigating protein interaction-based biological functions and neuroprotective mechanisms of Ngb. PMID- 22079574 TI - To believe or not to believe: trust choice modulates brain responses in outcome evaluation. AB - Making a trust decision in interpersonal relationship involves forming positive expectation toward the decision outcome. Previous studies have suggested that trust and distrust are qualitatively distinct and have differential neurocognitive substrates. In this study, we investigated how trust choice would modulate brain responses to decision outcome in a modified coin-toss game. Participants received statements from partners concerning the results of coin toss and decided whether to believe the truthfulness of the statements. In two experiments, event-related potentials (ERPs) to the real results revealed after the trust choice demonstrated differential patterns following trust and distrust choices. Both the feedback-related negativity (FRN) and the P300 showed effects of outcome valence following trust choices, but the FRN effect was reduced following distrust choices. Thus, trust choice creates different contexts in which aspects of decision outcome can be encoded simultaneously by the FRN. The FRN may reflect the subjective evaluation of decision outcome in a specific context rather than a general expectancy towards the outcome. PMID- 22079575 TI - alpha-synuclein phosphorylation and truncation are normal events in the adult human brain. AB - alpha-synuclein is a key protein in Lewy body diseases (LBDs) and a major component of Lewy bodies and related aberrant cytoplasmic and neuritic inclusions. Regional differences in alpha-synuclein have been associated with selective neuronal vulnerability to Lewy pathology. Furthermore, phosphorylation at serine 129 (Ser129) and alpha-synuclein truncation have been considered crucial in the pathogenesis of Lewy inclusions. The present study shows consistent reduction in alpha-synuclein protein expression levels in the human substantia nigra and nucleus basalis of Meynert compared with other brain regions independently of age and pathology. Phosphorylated alpha-synuclein at Ser129 is naturally increased in these same regions, thus inversely related with the total amount of alpha-synuclein. In contrast, truncated alpha-synuclein is naturally observed in control and diseased brains and correlating with the total amount of alpha-synuclein. Several truncated variants have been identified where some of these variants are truncated at the C-terminal domain, whereas others are truncated at the N-terminal domain, and all are present in cases with and without Lewy pathology. Although accumulation of truncated alpha-synuclein variants and phosphorylated alpha-synuclein occurs in Lewy bodies, alpha-synuclein phosphorylation and truncation can be considered constitutive in control and diseased brains. PMID- 22079576 TI - Nicotinic cholinergic mechanisms causing elevated dopamine release and abnormal locomotor behavior. AB - Firing rates of dopamine (DA) neurons in substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) control DA release in target structures such as striatum and prefrontal cortex. DA neuron firing in the soma and release probability at axon terminals are tightly regulated by cholinergic transmission and nicotinic acetylcholine receptors (nAChRs). To understand the role of alpha6* nAChRs in DA transmission, we studied several strains of mice expressing differing levels of mutant, hypersensitive (leucine 9' to serine [L9'S]) alpha6 subunits. alpha6 L9'S mice harboring six or more copies of the hypersensitive alpha6 gene exhibited spontaneous home-cage hyperactivity and novelty-induced locomotor activity, whereas mice with an equal number of WT and L9'S alpha6 genes had locomotor activity resembling that of control mice. alpha6-dependent, nicotine-stimulated locomotor activation was also more robust in high-copy alpha6 L9'S mice versus low-copy mice. In wheel-running experiments, results were also bi-modal; high-copy alpha6 L9'S animals exhibited blunted total wheel rotations during each day of a 9-day experiment, but low-copy alpha6 L9'S mice ran normally on the wheel. Reduced wheel running in hyperactive strains of alpha6 L9'S mice was attributable to a reduction in both overall running time and velocity. ACh and nicotine-stimulated DA release from striatal synaptosomes in alpha6 L9'S mice was well-correlated with behavioral phenotypes, supporting the hypothesis that augmented DA release mediates the altered behavior of alpha6 L9'S mice. This study highlights the precise control that the nicotinic cholinergic system exerts on DA transmission and provides further insights into the mechanisms and consequences of enhanced DA release. PMID- 22079577 TI - The opiate analgesic buprenorphine decreases proliferation of adult hippocampal neuroblasts and increases survival of their progeny. AB - Although opiate drugs of abuse have been shown to decrease adult hippocampal neurogenesis, the impact of opiate analgesics has not been tested. North American regulatory boards governing the ethical treatment of experimental animals require the administration of analgesics, such as buprenorphine, following minor surgical interventions. Here, we show that two commonly used post-operative buprenorphine dosing regimes significantly inhibit the proliferation of doublecortin-positive neuroblasts but not other hippocampal stem and progenitor cell populations in adult mice. Buprenorphine, administered in schedules of three 0.05 mg/kg subcutaneous injections over a single day or seven 0.05 mg/kg injections over a 3 day period decreased the number of actively proliferating 5-iodo-2'-deoxyuridine labeled doublecortin-positive cells for up to 6 days after opiate withdrawal. The minimal (three injection), but not standard (seven injection), analgesic paradigm also reduced basal indices of hippocampal progenitor cell apoptosis and enhanced survival of newly born cells for up to 28 days. Taken together, these data provide the first evidence that the routine administration of opiate analgesics has transient but long-lasting effects on neurogenesis and further emphasize that analgesic dosage and schedule should be reported and considered when interpreting the magnitude of neural stem and progenitor cell activation in response to in vivo intervention. PMID- 22079578 TI - Temporal and spatial regulation of interneuron distribution in the developing cerebral cortex--an in vitro study. AB - GABAergic interneurons are local circuit cells that control the excitatory balance in most regions of the nervous system, particularly the cerebral cortex. Because they are integrated in every cortical module, we posed the question whether interneuronal precursors would display some topographic specificity between their origin at the ventral telencephalon and their cortical location after migration. If this was true, GABAergic cells would have to be provided with intrinsic features that would make them able to perform specific functional roles in each specific module. On the other hand, if no topography was found, one would conclude that inhibitory precursors would be functionally naive, being able to integrate anywhere in the cortex, with equal capacity of performing their functions. This issue was approached by use of organotypic cultures of wild mice embryonic slices, into which fragments of the ganglionic eminence taken from enhanced green fluorescent protein (eGFP) mice were implanted, observing the topographic location of both the implant and its destination. Despite the existence of different genetic domains in the ventricular zone of the medial ganglionic eminences (MGE), we found that cells originating in different regions spread in vitro all over the mediolateral axis of the developing cortical wall, independently of their sites of origin. Results favor the hypothesis that GABAergic precursors are functionally naive, integrating into modules irrespective of which cortical area they belong to. PMID- 22079579 TI - Inducing pluripotency in somatic cells from the snow leopard (Panthera uncia), an endangered felid. AB - Induced pluripotency is a new approach to produce embryonic stem-like cells from somatic cells that provides a unique means to understand both pluripotency and lineage assignment. To investigate whether this technology could be applied to endangered species, where the limited availability of gametes makes production and research on embryonic stem cells difficult, we attempted generation of induced pluripotent stem (iPS) cells from snow leopard (Panthera uncia) fibroblasts by retroviral transfection with Moloney-based retroviral vectors (pMXs) encoding four factors (OCT4, SOX2, KLF4 and cMYC). This resulted in the formation of small colonies of cells, which could not be maintained beyond four passages (P4). However, addition of NANOG, to the transfection cocktail produced stable iPS cell colonies, which formed as early as D3. Colonies of cells were selected at D5 and expanded in vitro. The resulting cell line was positive for alkaline phosphatase (AP), OCT4, NANOG, and Stage-Specific embryonic Antigen-4 (SSEA-4) at P14. RT-PCR also confirmed that endogenous OCT4 and NANOG were expressed by snow leopard iPS cells from P4. All five human transgenes were transcribed at P4, but OCT4, SOX2 and NANOG transgenes were silenced as early as P14; therefore, reprogramming of the endogenous pluripotent genes had occurred. When injected into immune-deficient mice, snow leopard iPS cells formed teratomas containing tissues representative of the three germ layers. In conclusion, this was apparently the first derivation of iPS cells from the endangered snow leopard and the first report on induced pluripotency in felid species. Addition of NANOG to the reprogramming cocktail was essential for derivation of iPS lines in this felid. The iPS cells provided a unique source of pluripotent cells with utility in conservation through cryopreservation of genetics, as a source of reprogrammed donor cells for nuclear transfer or for directed differentiation to gametes in the future. PMID- 22079580 TI - Spices and energy balance. AB - The sensory properties of foods and beverages are primary determinants of food choice. Some flavor components have an inherent hedonic valence that influences ingestive behavior. However, these hedonic impressions may be modified and others newly formed through their association with the post-ingestive consequences of food and beverage consumption. Flavor-active compounds, including spices, also modify digestive, absorptive and metabolic processes through direct activation of signaling pathways or via neurally-mediated cephalic phase responses. These may modify energy balance through effects on food digestion, energy absorption and metabolism. Thus, collectively, flavor has the potential to modify energy balance. Attempts to purposefully augment energy and nutrient intake have largely focused on the aging population where flavor fortification is posited to correct for diminishing sensory function. Evidence of efficacy is not strong, possibly due to methodological issues such as low statistical power and failure to match documented sensory limitations with the nature of the intervention. More rigorous testing should determine the viability of this therapeutic application of food flavors. The use of flavor compounds for weight reduction has yielded mixed results. Most trials have delivered the compounds via capsule precluding assessment of flavor to outcomes. Work with red pepper suggests there is an independent, albeit subtle, sensory effect on substrate oxidation coupled with a more general reduction of appetite and enhancement of energy expenditure. Flavor active compounds hold some promise for being more a part of the solution than the problem of disordered eating and unhealthy weight. PMID- 22079581 TI - Sensitization of depressive-like behavior during repeated maternal separation is associated with more-rapid increase in core body temperature and reduced plasma cortisol levels. AB - Infant guinea pigs exhibit a 2-stage response to maternal separation: an initial active stage, characterized by vocalizing, and a second passive stage marked by depressive-like behavior (hunched posture, prolonged eye-closure, extensive piloerection) that appears to be mediated by proinflammatory activity. Recently we found that pups showed an enhanced (i.e., sensitized) depressive-like behavioral response during repeated separation. Further, core body temperature was higher during the beginning of a second separation compared to the first, suggesting a more-rapid stress-induced febrile response to separation the second day, though the possibility that temperature was already elevated prior to the second separation could not be ruled out. Therefore, the present study examined temperature prior to, and during, 2 daily separations. We also examined the temperature response to a third separation conducted 3 days after the second, and assessed the effect of repeated separation on plasma cortisol levels. Core temperature did not differ just prior to the separations, but showed a more-rapid increase and then decline during both a second and third separation than during a first. Temperature responses were not associated with changes in motor activity. Depressive-like behavior was greater during the second and third separations. Pups separated a first time showed a larger plasma cortisol response at the conclusion of separation than did animals of the same age separated a third time. In all, the results indicate that the sensitization of depressive-like behavior during repeated separations over several days is accompanied by a more-rapid febrile response that may be related to a reduction of glucocorticoid suppression. PMID- 22079583 TI - The lifespan consequences of early life stress. AB - Early life stress (ELS), an experience of severe stress due for example to parental loss, abuse or neglect during the childhood years, may have profound long-term effects on the individual's physiology and psychology. Here we review the findings of the Helsinki Birth Cohort Study 1934-44 (n=13,345), of whom approximately 14% were temporarily separated from both their parents due to child evacuations in World War II. The children were evacuated from Finland, unaccompanied by their parents, to other countries in Scandinavia (Sweden and Denmark) at the average age of 4.7 years (SD=2.4 years) and for an average period of 1.7 years (SD=1.0 years). Information on these separations for each member of the HBCS was derived from the Finnish National Archives. We found significant effects of ELS on psychiatric morbidity and mortality, intellectual ability, stress reactivity, reproductive history, and inter-generational social mobility. PMID- 22079584 TI - Mediators of allostasis and systemic toxicity in bipolar disorder. AB - Bipolar disorder is associated with a high rate of medical and psychiatric comorbidities. This burden of illness, along with cognitive impairment, is seen particularly in late cases, after multiple episodes. These changes in clinical presentation that take place over time have been recently conceptualized as "neuroprogression". The concept of allostatic load is instrumental in understanding how the cumulative stress associated with psychiatric disorders translates into bodily wear and tear, thus providing an underlying explanation for illness progression. Allostatic load is engendered by several factors which interact in a nonlinear manner. Glucocorticoids are fundamental mediators; when chronically in excess, glucocorticoids initiate a series of bodily dysfunctions that may include cortisol-related mitochondrial dysfunction, oxidative stress, inflammation and decrease in the expression of neuroprotective factors. In the present review we examine the role of allostatic load in the illness progression that takes place in bipolar disorder. PMID- 22079582 TI - Oxytocin, vasopressin and estrogen receptor gene expression in relation to social recognition in female mice. AB - Inter- and intra-species differences in social behavior and recognition-related hormones and receptors suggest that different distribution and/or expression patterns may relate to social recognition. We used qRT-PCR to investigate naturally occurring differences in expression of estrogen receptor-alpha (ERalpha), ER-beta (ERbeta), progesterone receptor (PR), oxytocin (OT) and receptor, and vasopressin (AVP) and receptors in proestrous female mice. Following four 5 min exposures to the same two conspecifics, one was replaced with a novel mouse in the final trial (T5). Gene expression was examined in mice showing high (85-100%) and low (40-60%) social recognition scores (i.e., preferential novel mouse investigation in T5) in eight socially-relevant brain regions. Results supported OT and AVP involvement in social recognition, and suggest that in the medial preoptic area, increased OT and AVP mRNA, together with ERalpha and ERbeta gene activation, relate to improved social recognition. Initial social investigation correlated with ERs, PR and OTR in the dorsolateral septum, suggesting that these receptors may modulate social interest without affecting social recognition. Finally, increased lateral amygdala gene activation in the LR mice may be associated with general learning impairments, while decreased lateral amygdala activity may indicate more efficient cognitive mechanisms in the HR mice. PMID- 22079585 TI - Adh1 and Adh1/4 knockout mice as possible rodent models for presymptomatic Parkinson's disease. AB - Alcohol dehydrogenases (ADH) catalyze the reversible metabolism of many types of alcohols and aldehydes to prevent the possible toxic accumulation of these compounds. ADHs are of interest in Parkinson's disease (PD) since these compounds can be harmful to dopamine (DA) neurons. Genetic variants in ADH1C and ADH4 have been found to associate with PD and lack of Adh4 gene activity in a mouse model has recently been reported to induce changes in the DA system. Adh1 knockout (Adh1-/-) and Adh1/4 double knockout (Adh1/4-/-) mice were investigated for possible changes in DA system related activity, biochemical parameters and olfactory function compared to wild-type (WT) mice. Locomotor activity was tested at ~7 (adult) and >15 months of age to mimic the late onset of PD. Adh1-/- and Adh1/4-/- mice displayed a significantly higher spontaneous locomotor activity than WT littermates. Both apomorphine and d-amphetamine increased total distance activity in Adh1-/- mice at both age intervals and in Adh1/4-/- mice at 7 months of age compared to WT mice. No significant changes were found regarding olfactory function, however biochemical data showed decreased 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratios in the olfactory bulb and decreased homovanillic acid (HVA)/DA ratios in the olfactory bulb, frontal cortex and striatum of Adh1/4-/- mice compared to WT mice. Our results suggest that lack of Adh1 alone or Adh1 and Adh4 together lead to changes in DA system related behavior, and that these knockout mice might be possible rodent models to study presymptomatic PD. PMID- 22079586 TI - Targeted gene delivery to the mouse brain by MRI-guided focused ultrasound induced blood-brain barrier disruption. AB - This study aimed to investigate the feasibility of targeted gene transfer into central nervous system (CNS) by MRI-guided focused ultrasound-induced blood-brain barrier (BBB) disruption. Before each sonication, T2-weighted images were obtained to select the target region. Followed by injecting DNA-loaded microbubbles into the tail vein, sonication was performed. The state of local BBB, distribution of plasmid DNA through the opened BBB, the ultrastructural changes of neurons and BDNF expression were detected. The results showed that MRI guided focused ultrasound (FUS) could accomplish noninvasive, transient, and local BBB disruption, at 1h after sonication, plasmid DNA across the opened BBB had been internalized into the neurons presenting heterogeneous distribution and numerous transparent vesicles were observed in the cytoplasm of the neurons at the sonicated region, suggesting vesicle-mediated endocytosis. At 48 h after sonication, the expressions of exogenous gene pBDNF-EGFP were observed in the cytoplasm of some neurons, and BDNF expressions were markedly enhanced by the combination of ultrasound and pBDNF-EGFP-loaded microbubbles about 20-fold than that of the control group (P<0.01). The method by using MRI-guided FUS to induce the local BBB disruption could accomplish effective targeted exogenous gene transfer in CNS. This technique may provide a new option for the treatment of various CNS diseases. PMID- 22079588 TI - The central versus peripheral antinociceptive effects of MU-opioid receptor agonists in the new model of rat visceral pain. AB - This study describes the antinociceptive effects of MU-opioid agonists, d Ala(2),N-Me-Phe(4),Gly(5)-ol-enkephalin (DAMGO) and morphine in a model of rat visceral pain in which nociceptive responses were triggered by 2% acetic acid intraperitoneal (i.p.) injections. DAMGO and morphine were administered i.p., to the same site where acetic acid was delivered or intracerebroventricularly (i.c.v.). The antinociceptive actions of i.p. versus i.c.v. administered DAMGO or morphine were evaluated in the late phase of permanent visceral nociceptive responses. Both compounds inhibited the nociceptive responses in a dose-dependent manner and exhibited more potent agonist activity after i.c.v. than i.p. administration. DAMGO and morphine showed comparable ED(50) values after i.p. injections. However, DAMGO was much stronger than morphine after central administration. Co-administration of the peripherally restricted opioid antagonist, naloxone methiodide (NAL-M), significantly attenuated the antinociceptive effects of i.p. DAMGO or morphine. On the other hand, i.c.v. injections of NAL-M partially antagonized the antinociceptive effect of i.p. morphine and failed to affect the antinociceptive action of i.p. DAMGO indicating the partial and pure peripheral antinociceptive effects of morphine and DAMGO, respectively. These results suggest the role of either central or peripheral MU opioid receptors (MOR) in mediating antinociceptive effects of i.p. MU-opioid agonists in the rat late permanent visceral pain model which closely resembles the clinical situation. PMID- 22079587 TI - System x(c)(-) regulates microglia and macrophage glutamate excitotoxicity in vivo. AB - It is widely believed that microglia and monocyte-derived macrophages (collectively referred to as central nervous system (CNS) macrophages) cause excitotoxicity in the diseased or injured CNS. This view has evolved mostly from in vitro studies showing that neurotoxic concentrations of glutamate are released from CNS macrophages stimulated with lipopolysaccharide (LPS), a potent inflammogen. We hypothesized that excitotoxic killing by CNS macrophages is more rigorously controlled in vivo, requiring both the activation of the glutamate/cystine antiporter (system x(c)(-)) and an increase in extracellular cystine, the substrate that drives glutamate release. Here, we show that non traumatic microinjection of low-dose LPS into spinal cord gray matter activates CNS macrophages but without causing overt neuropathology. In contrast, neurotoxic inflammation occurs when LPS and cystine are co-injected. Simultaneous injection of NBQX, an antagonist of AMPA glutamate receptors, reduces the neurotoxic effects of LPS+cystine, implicating glutamate as a mediator of neuronal cell death in this model. Surprisingly, neither LPS nor LPS+cystine adversely affects survival of oligodendrocytes or oligodendrocyte progenitor cells. Ex vivo analyses show that redox balance in microglia and macrophages is controlled by induction of system x(c)(-) and that high GSH:GSSG ratios predict the neurotoxic potential of these cells. Together, these data indicate that modulation of redox balance in CNS macrophages, perhaps through regulating system x(c)(-), could be a novel approach for attenuating injurious neuroinflammatory cascades. PMID- 22079589 TI - A current review of infection control for childhood tuberculosis. AB - Tuberculosis (TB) infection control recommendations in healthcare settings were developed to decrease nosocomial transmission from adults. In the absence of pediatric-specific guidelines, these infection control recommendations have been incorporated, in almost unmodified format, for childhood TB. We will review the evidence concerning the contagiousness of TB in children, scenarios in which transmission is more likely, review United States national recommendations, and consider the family unit, as opposed to the patient, to be the transmission unit for childhood TB. PMID- 22079590 TI - Toward a low-cost compact array microscopy platform for detection of tuberculosis. AB - This paper describes the development of a microscope array capable of imaging separate fields of view without the need for opto-mechanical scanning components. This microscope array can be integrated with array illuminating optics, a full frame digital single lens reflex (DSLR) camera, and automated algorithms for the detection of Mycobacterium tuberculosis (MTB). The entire array will fit within the area of a typical sputum smear. A custom miniature objective has been designed for this microscope array that has a numerical aperture of 0.5, optical resolution of 0.63 MUm, and a field of view that is 0.54 mm in diameter. A single prototype miniature objective of this design has been built, and images are presented demonstrating its imaging performance. Images are sufficiently high quality for diagnostic use. When fully integrated, this device has the potential to significantly improve performance compared to conventional microscopy systems and to enable more effective diagnosis of tuberculosis at the point of care. PMID- 22079591 TI - Ruscogenin inhibits lipopolysaccharide-induced acute lung injury in mice: involvement of tissue factor, inducible NO synthase and nuclear factor (NF) kappaB. AB - Acute lung injury is still a significant clinical problem with a high mortality rate and there are few effective therapies in clinic. Here, we studied the inhibitory effect of ruscogenin, an anti-inflammatory and anti-thrombotic natural product, on lipopolysaccharide (LPS)-induced acute lung injury in mice basing on our previous studies. The results showed that a single oral administration of ruscogenin significantly decreased lung wet to dry weight (W/D) ratio at doses of 0.3, 1.0 and 3.0 mg/kg 1 h prior to LPS challenge (30 mg/kg, intravenous injection). Histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells were also attenuated by ruscogenin. In addition, ruscogenin markedly decreased LPS-induced myeloperoxidase (MPO) activity and nitrate/nitrite content, and also downregulated expression of tissue factor (TF), inducible NO synthase (iNOS) and nuclear factor (NF)-kappaB p-p65 (Ser 536) in the lung tissue at three doses. Furthermore, ruscogenin reduced plasma TF procoagulant activity and nitrate/nitrite content in LPS-induced ALI mice. These findings confirmed that ruscogenin significantly attenuate LPS induced acute lung injury via inhibiting expressions of TF and iNOS and NF-kappaB p65 activation, indicating it as a potential therapeutic agent for ALI or sepsis. PMID- 22079592 TI - Deficiency of claudin-18 causes paracellular H+ leakage, up-regulation of interleukin-1beta, and atrophic gastritis in mice. AB - BACKGROUND & AIMS: Although defects in tight junction (TJ) epithelial paracellular barrier function are believed to be a primary cause of inflammation, the mechanisms responsible remain largely unknown. METHODS: We generated knockout mice of stomach-type claudin-18, a major component of TJs in the stomach. RESULTS: Cldn18(-/-) mice were afflicted with atrophic gastritis that started on postnatal day 3. This coincided with a decrease in intragastric pH due to H(+) secretion from parietal cells and concomitant up-regulation of the cytokines, interleukin-1beta, cyclooxygenase-2, and KC, resulting in spasmolytic polypeptide expressing metaplasia (SPEM). Oral administration of hydrochloric acid on postnatal day 1 induced the expression of these cytokines in Cldn18(-/-) infant stomach, but not in Cldn18(+/+) mice. A paracellular H(+) leak in Cldn18(-/-) stomach was detected by electrophysiology and H(+) titration, and freeze-fracture electron microscopy showed structural defects in the TJs, in which the tightly packed claudin-18 (stomach-type)-based TJ strands were lost, leaving a loose meshwork of strands consisting of other claudin species. CONCLUSIONS: These findings provide evidence that claudin-18 normally forms a paracellular barrier against H(+) in the stomach and that its deficiency causes paracellular H(+) leak, a persistent up-regulation of proinflammatory cytokines, chronic recruitment of neutrophils, and the subsequent development of SPEM in atrophic gastritis. PMID- 22079593 TI - The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten sensitized mice and human tissues. AB - BACKGROUND & AIMS: Copolymers of hydroxyethyl methacrylate and styrene sulfonate complex with isolated gliadin (the toxic fraction of gluten) and prevent damage to the intestinal barrier in HLA-HCD4/DQ8 mice. We studied the activity toward gluten and hordein digestion and biologic effects of poly(hydroxyethyl methacrylate-co-styrene sulfonate (P(HEMA-co-SS)). We also investigated the effect of gliadin complex formation in intestinal biopsy specimens from patients with celiac disease. METHODS: We studied the ability of P(HEMA-co-SS) to reduce digestion of wheat gluten and barley hordein into immunotoxic peptides using liquid chromatography-mass spectrometry. The biodistribution and pharmacokinetic profile of orally administered P(HEMA-co-SS) was established in rodents using tritium-labeled polymer. We assessed the capacity of P(HEMA-co-SS) to prevent the immunologic and intestinal effects induced by a gluten-food mixture in gluten sensitized HLA-HCD4/DQ8 mice after short-term and long-term administration. We measured the effects of gliadin complex formation on cytokine release ex vivo using intestinal biopsy specimens from patients with celiac disease. RESULTS: P(HEMA-co-SS) reduced digestion of wheat gluten and barley hordein in vitro, thereby decreasing formation of toxic peptides associated with celiac disease. After oral administration to rodents, P(HEMA-co-SS) was predominantly excreted in feces, even in the presence of low-grade mucosal inflammation and increased intestinal permeability. In gluten-sensitized mice, P(HEMA-co-SS) reduced paracellular permeability, normalized anti-gliadin immunoglobulin A in intestinal washes, and modulated the systemic immune response to gluten in a food mixture. Furthermore, incubation of P(HEMA-co-SS) with mucosal biopsy specimens from patients with celiac disease showed that secretion of tumor necrosis factor-alpha was reduced in the presence of partially digested gliadin. CONCLUSIONS: The copolymer P(HEMA-co-SS) reduced digestion of wheat gluten and barley hordein and attenuated the immune response to gluten in a food mixture in rodents. It might be developed to prevent or reduce gluten-induced disorders in humans. PMID- 22079594 TI - CCR9+ macrophages are required for acute liver inflammation in mouse models of hepatitis. AB - BACKGROUND & AIMS: Antigen-presenting cells (APCs) are involved in the induction of liver inflammation. We investigated the roles of specific APCs in the pathogenesis of acute liver injury in mice. METHODS: We used concanavalin A (con A) or carbon tetrachloride to induce acute liver inflammation in mice and studied the roles of macrophages that express CCR9. RESULTS: After injection of con A, we detected CCR9(+)CD11b(+)CD11c(-) macrophages that express tumor necrosis factor (TNF)-alpha in livers of mice, whereas CCR9(+)Siglec-H(+)CD11b(-)CD11c(low) plasmacytoid DCs (pDCs), which are abundant in normal livers, disappeared. The CCR9(+) macrophages were also detected in the livers of RAG-2(-/-) mice, which lack lymphocytes and natural killer T cells, after injection of con A. Under inflammatory conditions, CCR9(+) macrophages induced naive CD4(+) T cells to become interferon gamma-producing Th1 cells in vivo and in vitro. CCR9(-/-) mice injected with con A did not develop hepatitis unless they also received CCR9(+) macrophages from mice that received con A; more CCR9(+) macrophages accumulated in their inflamed livers than CCR9(+) pDCs, CCR9(-) pDCs, or CCR9(-) macrophages isolated from mice that had received injections of con A. Levels of CCL25 messenger RNA increased in livers after injection of con A; neutralizing antibodies against CCL25 reduced the induction of hepatitis by con A by blocking the migration of CCR9(+) macrophages and their production of TNF-alpha. Peripheral blood samples from patients with acute hepatitis had greater numbers of TNF-alpha-producing CCR9(+)CD14(+)CD16(high) monocytes than controls. CONCLUSIONS: CCR9(+) macrophages contribute to the induction of acute liver inflammation in mouse models of hepatitis. PMID- 22079595 TI - Severe defects in absorptive ion transport in distal colons of mice that lack ClC 2 channels. AB - BACKGROUND & AIMS: The fluid secretion model predicts that intestinal obstruction disorders can be alleviated by promoting epithelial Cl(-) secretion. The adenosine 3',5'-cyclic monophosphate (cAMP)-activated anion channel CFTR mediates Cl(-)-dependent fluid secretion in the intestine. Although the role of the ClC-2 channel has not been determined in the intestine, this voltage-gated Cl(-) channel might compensate for the secretory defects observed in patients with cystic fibrosis and other chronic constipation disorders. We investigated whether mice that lack ClC-2 channels (Clcn2(-/-)) have defects in intestinal ion transport. METHODS: Immunolocalization and immunoblot analyses were used to determine the cellular localization and the amount of ClC-2 expressed in mouse early distal colon (EDC) and late distal colon (LDC). Colon sheets from wild-type and Clcn2(-/-) littermates were mounted in Ussing chambers to determine transepithelial bioelectrical parameters and Na(+), K(+), and Cl(-) fluxes. RESULTS: Expression of ClC-2 was higher in the basolateral membrane of surface cells in the EDC compared with the LDC, with little expression in crypts. Neither cAMP nor Ca(2+)-induced secretion of Cl(-) was affected in the EDC or LDC of Clcn2(-/-) mice, whereas the amiloride-sensitive short-circuit current was increased approximately 3-fold in Clcn2(-/-) EDC compared with control littermates. Conversely, electroneutral Na(+), K(+), and Cl(-) absorption was dramatically reduced in colons of Clcn2(-/-) mice. CONCLUSIONS: Basolateral ClC-2 channels are required for colonic electroneutral absorption of NaCl and KCl. The increase in the amiloride-sensitive short-circuit current in Clcn2(-/-) mice revealed a compensatory mechanism that is activated in the colons of mice that lack the ClC-2 channel. PMID- 22079596 TI - Restricted heterochromatin formation links NFATc2 repressor activity with growth promotion in pancreatic cancer. AB - BACKGROUND & AIMS: Transcriptional silencing of the p15(INK4b) tumor suppressor pathway overcomes cellular protection against unrestrained proliferation in cancer. Here we show a novel pathway involving the oncogenic transcription factor nuclear factor of activated T cells (NFAT) c2 targeting a p15(INK4b)-mediated failsafe mechanism to promote pancreatic cancer tumor growth. METHODS: Immunohistochemistry, real-time polymerase chain reaction, immunoblotting, and immunofluorescence microscopy were used for expression studies. Cancer growth was assessed in vitro by [(3)H]thymidine incorporation, colony formation assays, and in vivo using xenograft tumor models. Protein-protein interactions, promoter regulation, and local histone modifications were analyzed by immunoprecipitation, DNA pull-down, reporter, and chromatin immunoprecipitation assays. RESULTS: Our study uncovered induction of NFATc2 in late-stage pancreatic intraepithelial neoplasia lesions with increased expression in tumor cell nuclei of advanced cancers. In the nucleus, NFATc2 targets the p15(INK4b) promoter for inducible heterochromatin formation and silencing. NFATc2 binding to its cognate promoter site induces stepwise recruitment of the histone methyltransferase Suv39H1, causes local H3K9 trimethylation, and allows docking of heterochromatin protein HP1gamma to the repressor complex. Conversely, inactivation of NFATc2 disrupts this repressor complex assembly and local heterochromatin formation, resulting in restoration of p15(INK4b) expression and inhibition of pancreatic cancer growth in vitro and in vivo. CONCLUSIONS: Here we describe a novel mechanism for NFATc2 mediated gene regulation and identify a functional link among its repressor activity, the silencing of the suppressor pathway p15(INK4b), and its pancreatic cancer growth regulatory functions. Thus, we provide evidence that inactivation of oncogenic NFATc2 might be an attractive strategy in treatment of pancreatic cancer. PMID- 22079597 TI - A coupled experimental and computational approach to quantify deleterious hemodynamics, vascular alterations, and mechanisms of long-term morbidity in response to aortic coarctation. AB - INTRODUCTION: Coarctation of the aorta (CoA) is associated with morbidity despite treatment. Although mechanisms remain elusive, abnormal hemodynamics and vascular biomechanics are implicated. We present a novel approach that facilitates quantification of coarctation-induced mechanical alterations and their impact on vascular structure and function, without genetic or confounding factors. METHODS: Rabbits underwent thoracic CoA at 10weeks of age (~9 human years) to induce a 20mmHg blood pressure (BP) gradient using permanent or dissolvable suture thereby replicating untreated and corrected CoA. Computational fluid dynamics (CFD) was performed using imaging and BP data at 32weeks to quantify velocity, strain and wall shear stress (WSS) for comparison to vascular structure and function as revealed by histology and myograph results. RESULTS: Systolic and mean BP was elevated in CoA compared to corrected and control rabbits leading to vascular thickening, disorganization and endothelial dysfunction proximally and distally. Corrected rabbits had less severe medial thickening, endothelial dysfunction, and stiffening limited to the proximal region despite 12weeks of normal BP (~4 human years) after the suture dissolved. WSS was elevated distally for CoA rabbits, but reduced for corrected rabbits. DISCUSSION: These findings are consistent with alterations in humans. We are now poised to investigate mechanical contributions to mechanisms of morbidity in CoA using these methods. PMID- 22079598 TI - Common interlimb asymmetries and neurogenic responses during upper limb neurodynamic testing: implications for test interpretation. AB - STUDY DESIGN: Clinical measurement pilot study. INTRODUCTION: Upper limb neurodynamic testing (ULNT1) uses interlimb comparisons to investigate nerve sensitivity to movement. PURPOSE OF THE STUDY: To establish the magnitude of range of motion asymmetries between limbs and the frequency of neurogenic sensory responses during ULNT1. METHODS: Elbow extension range of motion (EE-ROM) and sensory responses were measured during ULNT1 in dominant and nondominant limbs for 40 asymptomatic participants. Structural differentiation was performed to examine if sensory responses were associated with neurogenic sources. RESULTS: The average intraindividual EE-ROM asymmetry was 7.28 deg (6.68 standard deviation) (95% confidence interval: 5.18, 9.28). Sensory responses in the limbs during ULNT1 were altered by structural differentiation in 95% of participants. An intraindividual, interlimb difference of >=10 deg exceeds the range of common asymmetry during ULNT1. CONCLUSIONS: Neurogenic sensory responses are common findings in healthy individuals and should be acknowledged when interpreting ULNT1 findings. LEVEL OF EVIDENCE: 3a. PMID- 22079599 TI - [Computed tomography of the normal and pathologic temporal bone]. AB - High-resolution computed tomography scanning (CT) allows depiction of microanatomic structures of the temporal bone. CT is useful for detecting several pathologic conditions of the temporal bone such as congenital malformations, particularly in young children with sensorineural hearing loss. Some external, middle and inner ear structures are difficult to evaluate. The objective of this study has been to provide the key planes in coronal and axial planes (five coronal planes and three axial planes) but also with oblique planes reconstruction (two planes) for normal temporal bones evaluation. These standardized planes help to improve visualization of the main congenital malformations. Identification of obvious morphogenetic malformations (Michel aplasia, Mondini deformity....) is not difficult. However, less severe dysplasia may be missed or normal micro anatomic structures in newborn misreaded. PMID- 22079600 TI - [Absence of the musculocutaneous nerve and its distribution from median nerve: About two cases and literature review]. AB - Musculocutaneous nerve arises mostly from the lateral cord of brachial plexus. Nevertheless, variations have been reported and, among them: the total absence of musculocutaneous nerve (from 1.4 to 15%), the absence of its passage through the coracobrachial muscle, its variable level of penetration as measured from the tip of the coracoid process, and its communicating branches with the median nerve. We report two cases of unilateral musculocutaneous nerve absence in a 66-year-old male and a 95-year-old female cadavers, on the right and the left side, respectively. The nerve fibers normally coming from musculocutaneous nerve emerged from the median nerve. The knowledge of this anatomical variation is important specially when performing plexus bloc or Latarjet's procedure. PMID- 22079601 TI - Are all cases of low-grade mosaic trisomy 13 in amniotic fluid with no fetal malformation in fact confined placental mosaicism? A case report. AB - We report on a case of true prenatal mosaic trisomy 13 on amniotic fluid associated with a normal phenotype at the age of 6 years. The amniocentesis was performed because of advanced maternal age and was controlled by a second sample. Morphological and cardiac ultrasonography did not reveal any fetal malformations. No trisomic cells were found in the fetal blood and a nuclear magnetic resonance imaging (IRM) of the brain was performed during the third trimester found no abnormality of the brain. Finally, at birth cytogenetic analysis was performed on two placental samples for chromosomal analysis: one in an area where the placenta seemed normal, and the other one in an area with infarcted and hemorrhagic aspect. We found a high rate of trisomic cells in the sample with abnormal aspect. Furthermore, no trisomic cell was observed by fluorescent in situ hybridation (FISH) on the buccal smears of the baby. We concluded to a confined placental mosaicism. The good outcome of the child aged 6 years confirms this diagnosis. So in the aim to predict a good development for the child in case of low rate mosaic trisomy 13 in amniotic fluid, we propose at birth: i) to take several samples from the placenta to confirm placental mosaicism; ii) to label by FISH buccal smears with a LSI 13 probe to prove that the baby is not a carrier of the trisomy. PMID- 22079602 TI - Pilot study of home self-administration of subcutaneous depo-medroxyprogesterone acetate for contraception. AB - BACKGROUND: Subcutaneous depo-medroxyprogesterone acetate (DMPA-SC) offers the possibility of self-administration. STUDY DESIGN: This is a pilot study of self administration of DMPA-SC. Existing users of the intramuscular preparation (DMPA IM) who wished to self-inject (n=64) were taught self-administration using DMPA SC. The main outcome was the continuation rate of the method at 12 months compared to a control group of existing users of DMPA-IM (n=64) who continued to attend a clinic to receive the method. Women's satisfaction with the method and the proportion of self-injections given at correct time were also determined. RESULTS: The 12-month discontinuation rate of the DMPA-SC group (12%) did not differ significantly from that of the DMPA-IM group (22%) (95% confidence intervals of 13%-33% and 6%-23% for DMPA-SC and DMPA-IM, respectively; p=.23). All self-injections were given within the appropriate interval. There was no significant difference in the proportion of women in either group who were satisfied with the method. CONCLUSION: Self-administration of DMPA-SC for contraception is feasible and is associated with similar continuation rates and satisfaction to clinician-administered DMPA-IM. PMID- 22079603 TI - Predictors of noncompliance in an oral contraceptive clinical trial. AB - BACKGROUND: This analysis was conducted to identify the participant characteristics associated with noncompliance in an oral contraceptive (OC) clinical trial. STUDY DESIGN: We studied ovarian suppression among normal-weight and obese women during the use of levonorgestrel (LNG)-containing combination OCs. Participants underwent twice weekly phlebotomy during the study cycle and received up to $360 for participation. Along with other study assays, we analyzed 903 specimens from 181 women to measure LNG to assess OC compliance. Consistently undetectable LNG levels indicated noncompliance. To evaluate predictors of OC noncompliance during this study, we compared the characteristics of compliant and noncompliant participants using multivariable logistic regression. We assigned each participant to a relative poverty level based on US census data; all other individual characteristics came directly from participant responses during the baseline interview. RESULTS: One hundred eighty-one women completed the study; 31 were noncompliant (17%). In multivariable analyses, poverty level was the strongest predictor of noncompliance. Compared with those women in the quartile with the lowest level of residential poverty, other women were far more likely to be noncompliant, especially women in the quartile with the greatest prevalence of poverty (adjusted odds ratio, 8.4; 95% confidence interval, 1.5-46.1). Additional factors associated with noncompliance were education level less than a bachelor's degree and Hispanic ethnicity. Other demographic and psychometric measures were not associated with compliance. CONCLUSIONS: We found that noncompliance was strongly associated with residential poverty level, an indirect measure of individual income. In the United States, poverty is associated with female obesity, Hispanic ethnicity and low education, which were also associated here with noncompliance. Study compensation may motivate poor individuals to participate in clinical trials for income. Noncompliance in clinical trials, particularly differential noncompliance, jeopardizes study validity. PMID- 22079604 TI - Music for surgical abortion care study: a randomized controlled pilot study. AB - BACKGROUND: The study objective was to explore the effect of music as an adjunct to local anesthesia on pain and anxiety during first-trimester surgical abortion. Secondary outcomes included patient satisfaction and coping. STUDY DESIGN: We conducted a randomized controlled pilot study of 26 women comparing music and local anesthesia to local anesthesia alone. We assessed pain, anxiety and coping with 11-point verbal numerical scales. Patient satisfaction was measured via a 4 point Likert scale. RESULTS: In the music group, we noted a trend toward a faster decline in anxiety postprocedure (p=.065). The music group reported better coping than the control group (mean+/-S.D., 8.5+/-2.3 and 6.2+/-2.8, respectively; p<.05). Both groups reported similarly high satisfaction scores. There were no group differences in pain. CONCLUSIONS: Music as an adjunct to local anesthesia during surgical abortion is associated with a trend toward less anxiety postprocedure and better coping while maintaining high patient satisfaction. Music does not appear to affect abortion pain. PMID- 22079605 TI - Self-administration of subcutaneous depot medroxyprogesterone acetate for contraception: feasibility and acceptability. AB - BACKGROUND: The objectives of the study were to assess feasibility, continuation rates and patient satisfaction with self-administration of subcutaneous depot medroxyprogesterone acetate (DMPA-SC). MATERIALS AND METHODS: The study included 50 DMPA-seeking women between the ages of 18 and 49 years enrolled at two Florida Planned Parenthood health centers. Participants were taught self-injection during their initial study visit and, upon proficiency, self-injected one dose in clinic. Participants then injected a series of three more doses outside the health center over 9 months. Continuation rates, feasibility and acceptability were determined by analysis of four postinjection surveys. RESULTS: Continuation of DMPA-SC at injection 4 was 74% (95% confidence interval 62%-86%). Overall, survey responses from the three at-home injections indicated the method to be convenient (95%), easy (87%) and recommendable to others (94%). Twenty percent of injections were met with difficulty, most commonly cited as plunger resistance. No pregnancies occurred in study. CONCLUSIONS: Continuation was high with DMPA-SC self-injection. Participants reported injection to be easy and convenient and are likely to recommend self-administration to other women. Device issues are one potential deterrent. PMID- 22079606 TI - In vitro cytotoxicity of Cu2+, Zn2+, Ag+ and their mixtures on primary human endometrial epithelial cells. AB - BACKGROUND: To avoid the inherent disadvantages of copper-containing intrauterine device (Cu-IUD) induced by free Cu2+, two other well-performing metal ions, namely, Ag+, with long-effective antimicrobial properties, and Zn2+, as an essential trace element, are being considered for use in the future as multifunctional IUDs. The purpose of this study was to assess the cytotoxicity of these metal ions and their mixtures on primary human endometrial epithelial cells (HEECs) cultured in vitro and to provide several choices of alternative potential materials for creating excellent IUDs in the future. STUDY DESIGN: With the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-formazan (MTT-f) production, the cytotoxic effects of single metal ions (Cu2+, Zn2+, Ag+) on HEECs after exposure for 24, 48 or 72 h were investigated, and the synergistic and antagonistic effects of two ions applied simultaneously were also assessed. RESULTS: The cytotoxicity of the metal ions on HEECs ranked as follows: Ag+>Cu2+>Zn2+. All combinations of those tested indicated that the Cu2++Zn2+ system exhibited an antagonistic effect absolutely, the Zn2++Ag+ system showed both antagonism and slight synergism, and asynergistic effect was observed in the Cu2++Ag+ system. CONCLUSION: From a perspective of favorable biocompatibility, Zn2+ and the Cu2++Zn2+ mixture showed evidence of potential components for use in future IUDs. Although having strong cytotoxicity, Ag+ with its low release rate and broad-spectrum antibiotic activity may also be considered. The study also demonstrated the relative stability of Cu2+ as a classic material of IUD. PMID- 22079607 TI - Second- and third-trimester termination of pregnancy in women with uterine scar - a retrospective analysis of 111 gemeprost-induced terminations of pregnancy after previous cesarean delivery. AB - BACKGROUND: This study was conducted to evaluate and analyze the efficacy and safety of using gemeprost for second- and third-trimester termination of pregnancy (TOP) in women with uterine scar due to previous cesarean section. STUDY DESIGN: Retrospective analysis of 111 medical TOPs for fetal anomaly or death at 14 to 34 weeks of gestation in women with a history of cesarean section was performed at a German tertiary care center from 2005 to 2009. Abortion was induced via intravaginal application of the prostaglandin analogue gemeprost (1 mg) every 6 h. RESULTS: One hundred eleven women with one (89.2%) or two (10.8%) previous cesarean sections underwent medical TOP with gemeprost. The median induction-to-expulsion interval was 18 h 24 min (range, 2 h 20 min-168 h 28 min), and in 34 (30.6%) cases, the induction interval was longer than 24 h. The overall incidence of severe complications was 9/111 (8.1%), including one case of silent uterine rupture (with the need for blood transfusion), four cases of atonic and three secondary hemorrhages and one case of peritonitis due to uterine perforation during curettage. Failure of induction (induction-to-expulsion >48 h) occurred in 11 cases (9.9%). CONCLUSION: Gemeprost-induced TOP in the second and third trimester in women with uterine scar due to previous cesarean section is effective and has a low complication rate. PMID- 22079608 TI - Inhibition of proprotein convertase 5/6 activity: potential for nonhormonal women centered contraception. AB - BACKGROUND: Proprotein convertase 5/6 (PC6) is critical for endometrial epithelial receptivity and stromal cell decidualization for embryo implantation in women. We hypothesized that inhibiting PC6 could block implantation for contraception. The aim of this study was to prove this concept using human cell models and rabbits. STUDY DESIGN: A potential PC6 inhibitor, C1239-PEG-Poly R, was biochemically confirmed to be a potent PC6 inhibitor. The potential contraceptive action of the inhibitor was then tested in decidualization of primary human endometrial stromal cells in a human trophoblast spheroid attachment model and in vivo in rabbits. RESULTS: The PC6 inhibitor C1239-PEG Poly R inhibited in a dose-dependent manner both decidualization and spheroid attachment. Vaginal delivery of 200 MUL of the inhibitor at a final concentration of 5 mM to rabbits over a 3-day period starting 6 days after mating resulted in a 60% decrease in implantation and, hence, pregnancy. CONCLUSIONS: This study presents proof of concept that PC6 inhibition has the potential to block embryo implantation, providing nonhormonal contraception for women. PMID- 22079609 TI - The catalytic phosphoinositol 3-kinase isoform p110delta is required for glioma cell migration and invasion. AB - Glioblastoma multiforme (GBM) is a highly invasive and aggressive primary brain tumour in which loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a negative regulator of PI3K signalling, is a common feature. PTEN/PI3K/Akt signalling is involved in the regulation of proliferation, apoptosis and cell migration. Deregulation of PI3K signalling is considered an essential driver in gliomagenesis. However, the role of different PI3K isoforms in glioma is still largely unclear. Here we show that the catalytic PI3K isoform p110delta is consistently expressed at a high level in various glioma cell lines. We used small interfering RNA to selectively deplete p110delta and to determine its tumourigenic roles in PTEN-deficient cells. Interestingly, knockdown of p110delta decreased the cell migration and invasion ability of all GBM cell lines tested. Mechanistically, p110delta knockdown reduced the protein levels of focal adhesion kinase and cell division cycle 42, key regulators of cellular migration. In contrast, pharmacologic inhibition of p110delta by IC87114 or CAL-101 also clearly impaired glioma cell migration but had no obvious effect on the invasion capacity thus pinpointing to possible kinase-dependent and -independent roles of p110delta in glioma pathology. In summary, our data provide novel evidence that in glioma cells p110delta is a key regulator of cell movement and thus may contribute to the highly invasive phenotype of GBM. Isoform specific targeting of PI3Kdelta may be beneficial in the treatment of glioblastoma multiforme by specifically inhibiting tumour cell migration capacity. PMID- 22079610 TI - Mutagenicity and genotoxicity of suspended particulate matter in the Seine river estuary. AB - Highly mutagenic compounds such as some PAHs have been identified in surface waters and sediments of the Seine river estuary. Suspended particulate matter (SPM) represents a dynamic medium that may contribute to the exposure of aquatic organisms to toxic compounds in the water column of the estuary. In order to investigate major sources of mutagenic contaminants along the estuary, water samples were taken at 25 m downstream of the outlet of an industrial wastewater treatment plant (WWTP). SPM samples were analyzed for their genotoxicity with two short-term tests, the Salmonella typhimurium mutagenicity assay (TA98+S9 mix) and the comet assay in the human HepG2 cell line. Sampling sites receiving effluents from a chemical dye industry and WWTP showed the highest mutagenic potencies, followed by petrochemical industries, petroleum refinery and pulp and paper mills. These data indicate that frame-shift mutagens are present in the Seine river estuary. Furthermore, the comet assay revealed the presence of compounds that were genotoxic for human hepatocytes (HepG2 cells). We also observed a high level of mutagenic potency in the sediment of the lower estuary (3 * 104 revertants/g). The source of mutagenic and genotoxic compounds seems to be associated with various types of effluents discharged in the Seine river estuary. Both test systems resulted in the same assessment of the genotoxicity of particulate matter, except for three of the 14 samples, underlying the complementarity of bioassays. PMID- 22079611 TI - Profile of the distal femur anterior cortex--a computer-assisted cadaveric study. AB - INTRODUCTION: Accurate positioning and sizing of the femoral component in total knee arthroplasty is important for stability and functional outcome. The purpose of the study was to evaluate the bony profiles of the distal anterior femoral cortex (AFC). MATERIALS AND METHODS: Anatomical bony landmarks on 50 adult cadaveric femora were collected. Critical points were used to identify the distal AFC surface. RESULTS: There were four anterior cortex profiles: (1) lateral side highest and medial side lowest (56%); (2) lowest height in median area (26%); (3) highest height in median area (14%); (4) medial side highest and lateral side lowest (4%). DISCUSSION: Anterior referencing in TKA needs to represent the anterior shape of the distal femoral cortex to prevent notching, femoro-patellar overstuffing or flexion gap mismanagement. Due to the variability of the AFC, surgeons have to carefully select the AFC landmark to be sure of avoiding complications. PMID- 22079612 TI - Is there a link between osteofibrous dysplasia and adamantinoma? AB - Because of the relative frequency of osteofibrous dysplasia (OFD) and the gravity of adamantinoma, it is important to know whether there is a link between these two entities. A young boy had been followed from the age of 5 years for OFD of the right tibia. At the age of 10, biopsy performed because of pain, revealed OFD like adamantinoma. Surgery was undertaken, with en bloc proximal tibial resection of 14 cm and reconstruction by free vascularized fibula and internal fixation. This observation illustrates the risk of evolution of OFD-like adamantinoma, showing the same unfavorable evolution as classic adamantinoma. Strict surveillance is mandatory in OFD, with systematic biopsy in case of onset of pain or increased tumor volume. PMID- 22079613 TI - Risk factors and impact of orthopaedic monitoring on the outcome of avascular necrosis of the femoral head in adults with sickle cell disease: 215 patients case study with control group. AB - INTRODUCTION: Sickle cell disease is a public health problem. The WHO has recommended that global management be implemented to reduce mortality and morbidity. Since no comprehensive care programme for bone and joint complications exists, the Caribbean Sickle Cell Disease Center added orthopaedic consultation to screen for and monitor these complications in 1992. HYPOTHESIS: Comprehensive medical and surgical care of patients with sickle cell disease will reduce the complications and disability associated with this disease. POPULATIONS AND METHODS: Two populations were compared to evaluate the impact of comprehensive disease management on the occurrence of avascular necrosis (AVN) of the femoral head (femoral head AVN). The case-control series, [E-1994], included 115 patients (58 SS and 57 S) without orthopaedic monitoring and was evaluated retrospectively. The other patient series, [E-2008], included 215 patients (94 SS and 121 SC) with systematic orthopaedic care and was followed prospectively. Age, gender, duration of follow-up, haemoglobin levels, genotype, pain before treatment, associated humerus AVN and leg ulcers were analysed. RESULTS: Femoral head AVN occurred in young adult patients (35.3 +/- 4 years for [E-1994] and 29 +/- 3.4 years for [E-2008]). Only elevated haemoglobin levels were associated with the occurrence of femoral head AVN, which suggests that increased blood viscosity contributes to the condition ([E-1994], P<0.0001; [E-2008], P=0.001). Treatment in [E-2008] patients reduced the number of femoral head AVN cases from 36.5% in [E-1994] to 14.4% in [E-2008] (P<0.0001). DISCUSSION: The prevention and management of femoral head AVN must include medical treatment of the disease to reduce the occurrence of painful vaso-occlusive crises, which are known to trigger femoral head AVN. The effectiveness of this programme hinged on identifying risk factors and using simple approaches (hydration, pain medication, rest and crutches) to manage painful joint crises before femoral head AVN appeared. These approaches could be implemented in disadvantaged countries where sickle cell disease is prevalent. CONCLUSION: By knowing the risk factors, symptomatic patients who are at risk for femoral head AVN can be identified and additional evaluations can be performed early on in cases of hip pain. PMID- 22079614 TI - Mechanistic profiling of the cAMP-dependent steroidogenic pathway in the H295R endocrine disrupter screening system: new endpoints for toxicity testing. AB - The need for implementation of effects on steroid synthesis and hormone processing in screening batteries of endocrine disruptive compounds is widely acknowledged. In this perspective, hormone profiling in the H295R adrenocortical cell system is extensively examined and recently OECD validated (TG 456) as a replacement of the minced testis assay. To further elucidate the complete mechanisms and endocrine responsiveness of this cell system, microarray-based gene expression profiling of the cAMP response pathway, one of the major pathways in steroidogenesis regulation, was examined in H295R cells. Next to the steroid synthesis pathway, a broader lipid metabolic pathway, including cholesterol uptake/biosynthesis, hormone metabolization and many hormone and nuclear receptors, are sensitive towards cAMP stimulation in this cell system. Moreover, these pathways were clearly dose and time responsive, indicating early regulation (10 h) of cholesterol uptake and mobilization genes and later expression (24-48 h) of cholesterol biosynthesis and steroid synthesis. Transcription network analysis suggested several important transcription factors that could be involved in regulation of the steroid hormone pathway, of which HNF4alpha, a broader lipid metabolism related transcription factor, might indicate some new transcription regulation patterns in this cell line. Overall we can conclude that the time dependent gene expression patterns of the strongly coordinated cholesterol supply and steroidogenesis pathways in the H295R cell system seem to reflect well the in vivo ACTH/cAMP signalling cascade in adrenal cells. Moreover, the completeness of the steroidogenic related pathways in terms of gene expression sensitivity, indicates the H295R cell line as a promising cell line in omics-based endocrine disruption screening. PMID- 22079615 TI - Protective effect of methylprednisolone on paraquat-induced A549 cell cytotoxicity via induction of efflux transporter, P-glycoprotein expression. AB - Paraquat (PQ) is the third most extensively used herbicide in the world, causing thousands of deaths due to accidental or intentional self-poisoning in developing countries. Although many therapeutic treatments for PQ-induced poisonings have been proposed and developed, the efficacy of these treatments is still poor and requires further investigation. Methylprednisolone (trade name Solumedrol, hereinafter MP) is a widely used steroid for the treatment of various diseases but the function of MP has not yet been studied in the context of PQ-induced intoxication. The aim of this study was to determine if MP can ameliorate PQ induced toxicity in an alveolar A549 cell line by inducing ATP-dependent transporter P-glycoprotein (P-gp) expression. P-gp expression and activity in the PQ-treated A549 cell line were enhanced by MP treatment and cytotoxicity by PQ was dramatically decreased. We also found that MP per se or together with PQ induced P-gp expression by both Western blot and qRT-PCR analyses. In addition, induced P-gp transporter was shown to improve the efflux effect on PQ-treated A549 cell lines as was demonstrated using the Calcein-AM fluorescence accumulation assay. In summary, MP induces the transmembrane ATP-dependent transporter P-gp expression, which greatly improves PQ-treated A549 cell viability, reduces accumulation of intracellular PQ and prevents PQ induced cytotoxicity but it should be further evaluated in in vivo studies. PMID- 22079616 TI - Hair analysis for biomonitoring of environmental and occupational exposure to organic pollutants: state of the art, critical review and future needs. AB - This paper presents the current state of the art in human hair analysis for the detection of organic pollutants associated with environmental and occupational exposure. The different chemical classes are reviewed with a special focus set on compounds that were only recently investigated. The importance of methods sensitivity and particularly the influence of this parameter on the results presented in previous publications is highlighted. This report also investigates the relevance of hair analysis as an indicator of subjects' level of exposure and underlines limitations that are still associated with this matrix. This study also presents a critical assessment of some specific aspects presented in the literature as well as future needs to strengthen the position of hair as a relevant biomarker of exposure to be used in epidemiological studies. PMID- 22079617 TI - Use of PCR-based assays for the detection of the adventitious agent porcine circovirus type 1 (PCV1) in vaccines, and for confirming the identity of cell substrates and viruses used in vaccine production. AB - Safety and quality are important issues for vaccines. Whereas reversion to virulence poses a safety risk with live attenuated vaccines, the potential for the presence of adventitious agents is also an issue of vaccine quality. The recent detection or porcine circovirus type 1 (PCV1) in human vaccines has further highlighted the importance of quality control in vaccine production. The purpose of this study was to use a novel conventional PCR to detect PCV1, and subsequently screen materials used in the manufacture of vaccines at Bharat Biotech International Limited, India. The genome or gene fragments of PCV1 were not detected in any of the vaccines and materials tested, including the live attenuated rotavirus vaccine candidate ROTAVAC((r)). Further, the identity of the cells and the viruses used as starting materials in the manufacture of these vaccines was confirmed by species-specific PCR or virus-specific RT-PCR, and no cross-contamination was detected in any case. The methods can be applied for regular in-house quality control screening of raw materials and seeds/banks, as well as formulated vaccines. PMID- 22079618 TI - Expression of the influenza M2 protein in three different eukaryotic cell lines. AB - Current influenza virus vaccines provide protection in part by antibodies induced to the two surface glycoproteins, the hemagglutinin and the neuraminidase. As a result of the continuous antigenic drift of these glycoproteins, a frequent update of the composition of influenza vaccines is required. The search for more conserved viral epitopes which would induce protective immunity against seasonal influenza viruses and eventually also to novel pandemic influenza viruses has a long history. The ectodomain of the Influenza A Virus M2 Protein has been identified as a possible candidate immunization against influenza. The present study describes the expression of cloned M2 gene in MDCK, HeLa, and COS-7 cells, i.e., in three established eukaryotic cell lines. The expression efficiency was demonstrated by immunofluorescent staining of transfected cells by ELISA, by SDS PAGE-, and by Western blot-analysis. High level of expression was observed in COS 7 cells. Expression in HeLa and MDCK cells was less efficient. The plasmids constructed in this study may, after modifications, be used for the production of a DNA vaccine. Alternatively the expression product could be refined and used as a purified antigen for the vaccine. Thus, the M2 recombinant protein provides an ideal product for further antigenic, biochemical, structural and functional characterization of the protein and for evaluating its potential for immunodiagnosis and in vaccine studies. PMID- 22079619 TI - Standardization of denaturing gradient gel electrophoresis (DGGE) for discrimination of Victoria and Yamagata lineages of influenza B. AB - In this study, a PCR-DGGE protocol was standardized in order to distinguish Victoria and Yamagata influenza B lineages directly from clinical samples. After routine multiplex PCR characterization, amplicons of the haemagglutinin gene bearing a 40bp-length GC clamp were generated by nested-PCR and analyzed by electrophoresis in 6% polyacrylamide gel with a 25-45% urea-formamide gradient. The results showed a perfect correlation between DGGE and phylogenetic analyses for all compared samples, besides some distinct profiles in Victoria and Yamagata groups that could be used to infer variability inside these groups. In summary, this DGGE protocol for the haemagglutinin gene is rapid, useful and efficient, being an alternative for discrimination between the influenza B lineages. PMID- 22079620 TI - Rapid detection of sacbrood virus in honeybee using ultra-rapid real-time polymerase chain reaction. AB - A real-time reverse transcription-polymerase chain reaction (qRT-PCR) assay was developed for the fast and highly sensitive detection of the sacbrood virus (SBV) genome and applied to honeybee samples. Using plasmid DNA containing a partial SBV genome and diluted serially, as few as 1*10(2)copies/MUl (correlation co efficiency >0.99) were detected by the qRT-PCR assay, whereas 1*10(3)copies/MUl were detected by the conventional RT-PCR assay. As a rapid detection method, ultra-rapid real-time PCR (URRT-PCR) was carried out with a GenSpector TMC-1000 silicon-glass chip-based thermal cycler, which has a 6MUl micro-chamber volume and a fast outstandingly heating/cooling rate. Using this method, 10(3)copies of pBX-SBV3.8 clone were detected within 17 min after 40 PCR cycles, including melting point analysis. To reduce the detection time for SBV, synthesis of the cDNA of the SBV genome from a honeybee sample was attempted for different reaction times and the cDNA was used as the template for URRT-PCR assays. The results indicated that a 5 min reaction time was sufficient to synthesize cDNA as the template for the SBV URRT-PCR assay. This study described a novel PCR-based method that is able to detect an RNA virus in environmental samples within 22 min, including reverse transcription, PCR detection and melting point analysis in real-time. PMID- 22079621 TI - Development and evaluation of a real-time RT-PCR assay for Sindbis virus detection. AB - Sindbis virus (SINV) is an arthropod-borne alphavirus found widely in Eurasia, Africa and Oceania. Clinical SINV infection, characterized by rash and arthritis, is reported primarily in Northern Europe. The laboratory diagnosis of SINV infection is based currently on serology. A one-step TaqMan((r)) real-time RT-PCR assay was developed for the detection of SINV and evaluated its clinical performance with acute-phase serum samples. The specificity and sensitivity of the real-time PCR assay were assessed using cell cultured Finnish SINV strains. The applicability of the assay for diagnostic use was evaluated using 58 serum samples from patients infected with SINV. The real-time RT-PCR assay was specific and sensitive for the detection of SINV in cell culture supernatants with a 95% detection limit of 9 genome copies/reaction determined by probit analysis. However, in the assay only 7/58 (12%) of serum samples were positive of which two were also positive by conventional nested PCR assay and none by virus isolation. This novel assay is specific and sensitive for detection of SINV and can be used for example for screening SINV in wildlife. However, molecular diagnostic techniques using serum samples seem to be of limited value for the diagnosis of human SINV infection due to the short and low viraemia of infection with SINV. PMID- 22079622 TI - Ethnic differences in burn mechanism and severity in a UK paediatric population. AB - BACKGROUND: Burns in children are a major public health problem with long-lasting physical and psychological sequelae. Previous studies have identified that children from ethnic minorities have higher rates of burns. OBJECTIVE: The purpose of this study was to analyse the differences in paediatric burn mechanism and severity within different ethnic groups. METHODS: Demographic and burn data from all paediatric patients presenting with burn at the Burns Service, Alder Hey Children's NHS Foundation Trust, Liverpool, UK were collected over a 5 year period. RESULTS: 766 paediatric patients (age range: 7 days to 16 years old, mean: 4.5 years) were included in the study. Ethnic minority children had higher total body surface area of burn (p<0.001) and length of stay (p<0.001) compared with non-ethnic minority children. Chinese children had most burns from hot food (60%), whereas non-ethnic minority children had most burns from hot beverages (35.8%). Ethnic minority children were more deprived compared with non-ethnic minority children (Index of Multiple Deprivation 48.7 vs. 40.9; p=0.02). CONCLUSION: These results show that there are significant differences in the patterns of burns in ethnic minority groups. This data should guide targeted public health prevention and educational strategies. PMID- 22079623 TI - Developing the first Bi-National clinical quality registry for burns--lessons learned so far. AB - BACKGROUND: Prior to 2004, Australia and New Zealand lacked a systematic method to measure burn incidence, aetiology and quality of care or outcomes for burn patients. The Australian and New Zealand Burn Association (ANZBA) commenced the Bi-National Burns Registry (Bi-NBR) at that time. As a result of the limitations identified with the registry, ANZBA collaborated with Monash University to develop the registry as a clinical quality registry [1]. METHOD: A Steering Committee was formed to oversee the conduct and development of the registry. A Reference Committee revised the minimum dataset and working parties developed clinical quality indicators, and an outcome pilot project. RESULTS: Institutional ethics approval has been obtained for 16 out of 17 sites and a formalised governance process developed. The minimum dataset was improved and includes clinical quality indicators. The Bi-NBR clinical quality registry was launched on July 1st 2009. A long-term outcome pilot project has been developed with five burn units participating (recruitment commenced October 2009). CONCLUSION: Through a rigorous development process, a clinical quality registry for burns has been established which allows benchmarking of processes and outcomes between units. The intention is that all burns units across Australia and New Zealand will contribute to the registry. PMID- 22079624 TI - Exploring the mother's perception of latching difficulty in the first days after birth: an interview study in an Italian hospital. AB - OBJECTIVES: to explore Italian mothers' perception of latching difficulty in the first days postpartum. Latching difficulty is the only qualitative item included in the Breastfeeding Assessment Score (BAS) that has proven to be a valid instrument to identify women at risk of early breast-feeding cessation. DESIGN AND SETTING: a phenomenologic-hermeneutic study was conducted at the Mangiagalli Clinic, Milan, Italy. PARTICIPANTS: fifteen women who received a BAS <8 (indicating an early breast-feeding cessation risk) were interviewed before discharge, and later by phone, for member checking. FINDINGS: six main themes emerged from the interviews: (1) Breast feeding can be difficult due to both the mother and newborn, and encountered problems are mainly physical. (2) Women have developed different strategies to overcome latching difficulties. (3) Early breast feeding, even if difficult, is mostly related to positive feelings. (4) Breast-feeding sustains the child-mother relationship. (5) Mothers have already developed constructive theories about human colostrum, breast milk and artificial milk. (6) Receiving integrated health-care support and education is fundamental to overcome early breast-feeding problems. CONCLUSIONS: the interviews suggest that although mothers experience difficulties during early breast feeding, positive feelings seem to prevail over the negative ones, and mothers have already developed strategies to overcome their latching problems. Receiving support is fundamental, but this must be consistent among health-care professionals. IMPLICATIONS FOR PRACTICE: when evaluating the BAS item 'latching difficulty', midwives should consider that difficulties are primarily related to physical problems. Furthermore, to sustain lactation, mothers should be helped to elicit their experience of early breast feeding, as it can be extremely satisfying, even when difficulties in latching the babies occur. PMID- 22079625 TI - Reproductive health services in Malawi: an evaluation of a quality improvement intervention. AB - OBJECTIVE: this study was to evaluate the impact of a quality improvement initiative in Malawi on reproductive health service quality and related outcomes. DESIGN: (1) post-only quasi-experimental design comparing observed service quality at intervention and comparison health facilities, and (2) a time-series analysis of service statistics. SETTING: sixteen of Malawi's 23 district hospitals, half of which had implemented the Performance and Quality Improvement (PQI) intervention for reproductive health at the time of the study. PARTICIPANTS: a total of 98 reproductive health-care providers (mostly nurse midwives) and 139 patients seeking family planning (FP), antenatal care (ANC), labour and delivery (L&D), or postnatal care (PNC) services. INTERVENTION: health facility teams implemented a performance and quality improvement (PQI) intervention over a 3-year period. Following an external observational assessment of service quality at baseline, facility teams analysed performance gaps, designed and implemented interventions to address weaknesses, and conducted quarterly internal assessments to assess progress. Facilities qualified for national recognition by complying with at least 80% of reproductive health clinical standards during an external verification assessment. MEASUREMENTS: key measures include facility readiness to provide quality care, observed health-care provider adherence to clinical performance standards during service delivery, and trends in service utilisation. FINDINGS: intervention facilities were more likely than comparison facilities to have the needed infrastructure, equipment, supplies, and systems in place to offer reproductive health services. Observed quality of care was significantly higher at intervention than comparison facilities for PNC and FP. Compared with other providers, those at intervention facilities scored significantly higher on client assessment and diagnosis in three service areas, on clinical management and procedures in two service areas, and on counselling in one service area. Service statistics suggest that the PQI intervention increased the number of Caesarean sections, but showed no impact on other indicators of service utilisation and skilled care. CONCLUSIONS: the PQI intervention showed a positive impact on the quality of reproductive health services. The effects of the intervention on service utilisation had likely not yet been fully realized, since none of the facilities had achieved national recognition before the evaluation. Staff turnover needs to be reduced to maximise the effectiveness of the intervention. IMPLICATIONS FOR PRACTICE: the PQI intervention evaluated here offers an effective way to improve the quality of health services in low-resource settings and should continue to be scaled up in Malawi. PMID- 22079626 TI - A hermeneutic phenomenological study of Belgian midwives' views on ideal and actual maternity care. AB - OBJECTIVE: to explore midwives' views on ideal and actual maternity care. DESIGN: a qualitative hermeneutic phenomenological study based on the method of van Manen (1997) using individual in-depth interviews to gather data. SETTING: Flanders, Belgium. PARTICIPANTS: 12 purposively sampled midwives, of whom nine from three different non-university hospitals and three independent midwives conducting home births. FINDINGS: five major themes were identified: 'woman-centred care', 'cultural change', 'support', 'midwife and obstetrician as equal partners' and 'inter-collegial harmony'. In this paper 'woman-centred care', 'cultural change' and 'support' are discussed along with their subthemes. Midwives thought ideal maternity care should be woman-centred in which there were no unnecessary interventions, women were able to make an informed choice and there was continuity of care. Furthermore, ideal maternity care should be supported by midwifery education and an adequate staffing level. Also, a cultural change was wanted as actual maternity care was perceived to be highly medicalised. Barriers to achieving woman-centred care and possible strategies to overcome these were described. CONCLUSIONS: findings from this study were consistent with those of other studies on midwives' experience with obstetric-led care. Despite the medicalised care, midwives still held a woman-centred ideology. In order to be able to work according to their ideology, different barriers need to be addressed. Although midwives suggested strategies to overcome these barriers, some were considered to be very difficult to overcome. PMID- 22079627 TI - Identification of alternatively spliced multiple transcripts of 5 hydroxytryptamine receptor in mouse. AB - 5-Hydroxytryptamine receptors (HTRs) are coded by seventeen different genes in mouse. One of them is htr4 that codes for the HTR4 receptor, a G-protein coupled receptor containing seven transmembrane domains. In mouse, the gene is reported to contain 6 exons and 5 introns. Our present study reports the presence of four transcript variants of this gene encoding different N-termini. These transcripts are expressed in neuronal as well as non-neuronal tissues of mouse. We have identified five novel coding exons present at the 5' end of the gene which splice with the published internal exon in an alternative manner making a total of five transcripts, four new transcript variants (T1, T2l, T2s and T3) and one published earlier. All five transcripts encoding different N-termini were expressed in mouse brain. It was interesting to note the expression of only T3 transcript that was also detected in heart muscle and is the only htr4 transcript expressed in heart. For the first time a transcript of htr4 gene was detected in the heart of the mouse which might help us to make use of small laboratory animals to study HTR4 in heart. As this transcript is unique to the heart it can serve as potential therapeutic target for various cardiovascular disorders and dysregulation of heart rate, atrial contraction and atrial relaxation. These variants display heterogeneous properties in terms of the presence of signal peptide, acetylation, phosphorylation and glycosylation. Thus alternative splicing of htr4 producing heterogeneous N-termini increases the diversity of the receptor. PMID- 22079628 TI - Sigma-1Rs are upregulated via PERK/eIF2alpha/ATF4 pathway and execute protective function in ER stress. AB - Sigma-1 receptors (Sig-1Rs) are the ER resident proteins. Sig-1Rs in the brain have been reported to be significantly reduced in patients with schizophrenia. The impediment of regulating Sig-1Rs expression levels increases the risk for schizophrenia. Thus elucidating the mechanism regulating Sig-1Rs expression might provide the strategy to prevent mental disorders. In this study, we have demonstrated that Sig-1Rs were transcriptionally upregulated by ATF4 in ER stress. Moreover, ATF4 directly bounds to the 5' flanking region of Sig-1R gene. The reporter activities using this region were enhanced in ER stress, or by ATF4 alone. The reporter activities with the pathogenic polymorphisms (GC-241-240TT, T 485A) were reduced. In addition, the processing of Caspase-4 was inhibited by Sig 1Rs. These results indicate that Sig-1Rs are transcriptionally upregulated via the PERK/eIF2alpha/ATF4 pathway and ameliolate cell death signaling. This study is the first report identifying the transcription factor regulating Sig-1Rs expression. PMID- 22079629 TI - Tetraspanins regulate the protrusive activities of cell membrane. AB - Tetraspanins have gained increased attention due to their functional versatility. But the universal cellular mechanism that governs such versatility remains unknown. Herein we present the evidence that tetraspanins CD81 and CD82 regulate the formation and/or development of cell membrane protrusions. We analyzed the ultrastructure of the cells in which a tetraspanin is either overexpressed or ablated using transmission electron microscopy. The numbers of microvilli on the cell surface were counted, and the radii of microvillar tips and the lengths of microvilli were measured. We found that tetraspanin CD81 promotes the microvillus formation and/or extension while tetraspanin CD82 inhibits these events. In addition, CD81 enhances the outward bending of the plasma membrane while CD82 inhibits it. We also found that CD81 and CD82 proteins are localized at microvilli using immunofluorescence. CD82 regulates microvillus morphogenesis likely by altering the plasma membrane curvature and/or the cortical actin cytoskeletal organization. We predict that membrane protrusions embody a common morphological phenotype and cellular mechanism for, at least some if not all, tetraspanins. The differential effects of tetraspanins on microvilli likely lead to the functional diversification of tetraspanins and appear to correlate with their functional propensity. PMID- 22079631 TI - Myostatin induces autophagy in skeletal muscle in vitro. AB - Myostatin is an important regulator of muscle mass that contributes to the loss of muscle mass in a number of chronic diseases. Myostatin is known to activate the expression of components of the ubiquitin-proteosomal pathway but its effect on the autophagic pathway is not known. We therefore analysed the effect of myostatin and TGF-beta on autophagy in C2C12 cells by determining the effect of these proteins on LC3 processing, autophagosome formation and autophagy gene expression. Both myostatin and TGF-beta increased LC3II expression and turnover as well as autophagosome formation (marked by the formation of puncta in LC3-GFP transfected cells). Myostatin also significantly increased the expression of ATG 4B and ULK-2 mRNA while TGF-beta caused a trend towards an increase in these genes. We conclude that myostatin and TGF-beta increase autophagy in skeletal muscle cells. PMID- 22079630 TI - Reduction in number of sarcolemmal KATP channels slows cardiac action potential duration shortening under hypoxia. AB - The cardiovascular system operates under demands ranging from conditions of rest to extreme stress. One mechanism of cardiac stress tolerance is action potential duration shortening driven by ATP-sensitive potassium (K(ATP)) channels. K(ATP) channel expression has a significant physiologic impact on action potential duration shortening and myocardial energy consumption in response to physiologic heart rate acceleration. However, the effect of reduced channel expression on action potential duration shortening in response to severe metabolic stress is yet to be established. Here, transgenic mice with myocardium-specific expression of a dominant negative K(ATP) channel subunit were compared with littermate controls. Evaluation of K(ATP) channel whole cell current and channel number/patch was assessed by patch clamp in isolated ventricular cardiomyocytes. Monophasic action potentials were monitored in retrogradely perfused, isolated hearts during the transition to hypoxic perfusate. An 80-85% reduction in cardiac K(ATP) channel current density results in a similar magnitude, but significantly slower rate, of shortening of the ventricular action potential duration in response to severe hypoxia, despite no significant difference in coronary flow. Therefore, the number of functional cardiac sarcolemmal K(ATP) channels is a critical determinant of the rate of adaptation of myocardial membrane excitability, with implications for optimization of cardiac energy consumption and consequent cardioprotection under conditions of severe metabolic stress. PMID- 22079632 TI - Characterization of residues in the cytoplasmic domain of the LDL receptor required for exit from the endoplasmic reticulum. AB - Newly synthesized low density lipoprotein receptors (LDLRs) exit the endoplasmic reticulum (ER) as the first step in the secretory pathway. In this study we have generated truncating deletions and substitutions within the 50 amino acid cytoplasmic domain of the LDLR in order to identify residues required for the exit from the ER. Western blot analysis was used to determine the relative amounts of the 120 kDa precursor form of the LDLR located in the ER and the 160 kDa mature form that has exited the ER. These studies have shown that the exit of an LDLR lacking the cytoplasmic domain, is markedly reduced. Moreover, the longer the cytoplasmic domain, the more efficient is the exit from the ER. At least 30 residues were required for the LDLR to efficiently exit the ER. Mutations in the two di-acidic motifs ExE(814) and/or ExD(837) had only a small effect on the exit from the ER. The requirement for a certain length of the cytoplasmic domain for efficient exit from the ER, could reflect the distance needed to interact with the COPII complex of the ER membrane or the requirement for the LDLR to undergo dimerization. PMID- 22079633 TI - The intriguing enhancement of chloroperoxidase mediated one-electron oxidations by azide, a known active-site ligand. AB - Azide is a well-known inhibitor of heme-enzymes. Herein, we report the counter intuitive observation that at some concentration regimes, incorporation of azide in the reaction medium enhances chloroperoxidase (CPO, a heme-enzyme) mediated one-electron abstractions from several substrates. A diffusible azidyl radical based mechanism is proposed for explaining the phenomenon. Further, it is projected that the finding could have significant impact on routine in situ or in vitro biochemistry studies involving heme-enzyme systems and azide. PMID- 22079634 TI - Characterization of neuritin as a novel angiogenic factor. AB - Neuritin (NRN1), a neurotrophic factor, plays an important role in neurite growth and neuronal survival. In this study, we identify a new function of neuritin as a novel angiogenic factor in vitro and in vivo. Recombinant neuritin protein had no effect on the proliferation and adhesion of human umbilical vein endothelial cells (HUVEC), but it dose-dependently increased endothelial cell migration. Furthermore, overexpression of neuritin significantly promoted tumor angiogenesis, and surprisingly, it inhibited tumor growth in a xenograft tumor model. Thus, our results indicate that neuritin may act as an important angiogenic factor and serve as a potential target for cancer therapy. PMID- 22079635 TI - Regulation of MMP10 expression by the transcription factor CHF1/Hey2 is mediated by multiple E boxes. AB - The cardiovascular restricted bHLH transcription factor CHF1/Hey2 has been reported to play an important role in regulation of vascular smooth muscle phenotype and gene expression, but the downstream target genes that mediate these effects have not been completely elucidated. We have previously found that loss of CHF1/Hey2 in vascular smooth muscle cells leads to dysregulated expression of the matrix metalloproteinase gene MMP10 after treatment with PDGF. Here we report that loss or knockdown of CHF1/Hey2 in vascular smooth muscle cells leads to increased expression and activity of MMP10 at baseline, suggesting a direct effect of CHF1/Hey2 on MMP10 promoter regulation. To test this hypothesis, we assessed the effects of CHF1/Hey2 on a 2.5 kb MMP10 promoter region upstream of the transcriptional start site. We found that this region contains multiple elements including 12 E-boxes that mediate constitutive activity and repression by CHF1/Hey2 in 293T cells and A7r5 smooth muscle cells. Surprisingly, mutation of these E-boxes not only abolished CHF1/Hey2 repression, but also diminished constitutive expression. In addition, we observed that some of these mutations unmasked an activator function for CHF1/Hey2, which has not been previously described. These findings support the hypothesis that CHF1/Hey2 is an important regulator of MMP10 expression. PMID- 22079636 TI - Barrier characteristics of epithelial cultures modelling the airway and intestinal mucosa: a comparison. AB - The barrier characteristics of polarized layers of Calu-3 and Caco-2 cell lines, as commonly used in vitro models of intestinal and airway mucosa, respectively, were investigated by assessing the translocation of model macromolecules and nanoparticles. The barrier capacity of the cell layers towards the movement of macromolecules and nanoparticulates differed considerably between the cell lines. Permeability studies revealed the existence of a notably larger solute molecular weight limit for paracellular diffusion in Caco-2 monolayers compared to Calu-3 cells. Removal of mucus in Calu-3 cells resulted in cell layers exhibiting a larger macromolecular permeability, in addition to improved nanoparticle translocation. Microscopic examination of the tight junctions, as cellular features that play a major role in preventing transepithelial movement of macromolecules, revealed that the appearance of cell-cell boundaries was notably different in the two cell lines, which could explain the differences in macromolecular permeability. The data overall showed that epithelial layers of airway Calu-3 and intestinal Caco-2 cell cultures in vitro exhibit a different level of restrictiveness and this is due to the cell morphology and the presence of mucus. PMID- 22079637 TI - Structure-activity relationship of T-cell receptors based on alanine scanning. AB - T-cell receptors (TCR) recognize complexes between human leukocyte antigens (HLA) and peptides derived from intracellular proteins. Their therapeutic use for antigen targeting, however, has been hindered by the very low binding affinity of TCRs, typically in the 1- to 100-MUM range. Therefore, to construct mutant TCRs with high binding affinity, we need to understand the relationship between the structure and activity of these molecules. Here, we attempted to identify the amino acids of the TCR that are important for binding to the peptide/HLA complex. We used a TCR that recognizes complexes between HLA-A(*)0201 and the peptide from tyrosinase, antigen overexpressed in melanoma. We changed 16 amino acids in the third complementarity-determining region within the TCR to alanine and examined the effect on binding affinity. Five alanine substitutions decreased the binding affinity to below 10% compared with that of wild-type TCR. In contrast, one alanine substitution caused a faster on-rate and slower off-rate, and increased the binding affinity to three times that of the wild-type TCR. Our results provide fundamental information for constructing mutant TCRs with high binding affinity. PMID- 22079638 TI - MicroRNA-34a regulates migration of chondroblast and IL-1beta-induced degeneration of chondrocytes by targeting EphA5. AB - MicroRNAs function as an endogenous mode of fine gene regulation and have been implicated in multiple differentiation and developmental processes. In the present study, we investigated the role of miRNA-34 during chondrogenic differentiation of chick limb mesenchymal cells. We found that the expression of miR-34a increased upon chondrogenic inhibition. Blockade of miR-34a via PNA-based antisense oligonucleotides (ASOs) recovered the chondro-inhibitory actions of JNK inhibitor on migration of chondrogenic progenitors and the formation of precartilage condensation. Furthermore, we determined that EphA5 is a relevant target of miR-34a during chondrogenesis. MiR-34a was necessary and sufficient to down-regulate EphA5 expression, and up-modulation of EphA5 is sufficient to overcome inhibitory actions of miR-34 inhibition on cell migration and condensation of chick limb mesenchymal cells on collagen substrate. Taken together, our data suggest that miR-34a is a negative modulator of chondrogenesis, particularly in migration of chondroblasts, by targeting EphA5 and resulting inhibition of cellular condensation during chondrogenesis of chick limb mesenchymal cells. PMID- 22079639 TI - Differential expression of nanog1 and nanogp8 in colon cancer cells. AB - Nanog, a homeodomain transcription factor, is an essential regulator for promotion of self-renewal of embryonic stem cells and inhibition of their differentiation. It has been demonstrated that nanog1 as well as nanogp8, a retrogene of nanog1, is preferentially expressed in advanced stages of several types of cancer, suggesting their involvement during cancer progression. Here, we investigated the expression of Nanog in well-characterized colon cancer cell lines. Expression of Nanog was detectable in 5 (HCT116, HT29, RKO, SW48, SW620) out of seven cell lines examined. RNA expression analyses of nanog1 and nanogp8 indicated that, while nanog1 was a major form in SW620 as well as in teratoma cells Tera-2, nanogp8 was preferentially expressed in HT29 and HCT116. In accordance with this, shRNA-mediated knockdown of nanog1 caused the reduction of Nanog in SW620 but not in HT29. Inhibition of Nanog in SW620 cells negatively affected cell proliferation and tumor formation in mouse xenograft. Biochemical subcellular fractionation and immunostaining analyses revealed predominant localization of Nanog in cytoplasm in SW620 and HT29, while it was mainly localized in nucleus in Tera-2. Our data indicate that nanog1 and nanogp8 are differentially expressed in colon cancer cells, and suggest that their expression contributes to proliferation of colon cancer cells. PMID- 22079640 TI - [Diagnostic value of clinical signs and clinical scoring for deep vein thrombosis after hip and knee arthroplasty]. AB - AIM: To assess the most accurate clinical signs and clinical scoring for selecting patients who could benefit from duplex sonography screening of deep venous thrombosis (DVT) after total hip replacement (THR) and total knee replacement (TKR). METHODS: Four hundred and eighty consecutive patients with THR or TKR were included. Post-operative physical examination and venous duplex sonography (day 6-10) were performed in all of them. DVT was diagnosed in presence of at least 3mm thick and 3 cm long incomplete venous compressibility. Clinical prediction scores were built from clinical parameters, which were significantly associated with DVT in univariate analysis, one of them weighted from logistic multivariate regression coefficients. RESULTS: Recent DVT was diagnosed in 74 patients (15.7%) (29.6% after TKR and 8.4% after THR). There was no isolated proximal DVT and extensive DVTs were very rare (TKR 1.2% vs. THR 1%). Two TKR patients developed pulmonary embolism (1.2%). One died (0.6%). Univariate analysis showed significant association between provoked localized limb pain, pitting edema and difference in calf circumference (DCC), and DVT (P<0.0001). DCC> 3 cm was significantly associated with DVT (32.4% vs. 16.6%, OR 2.4 [1.3 4.2] ; P=0.001). In multivariate analysis the only two clinical manifestations independently associated with DVT were provoked localized limb pain (adjusted OR 2.3 [1.3-4.1] ; P<0.01) and DCC> 3 cm (adjusted OR 2.0 [1.1-3.8] ; P=0.04). A clinical score value greater or equal to 4 was associated with a risk of DVT of 34%, and a value<4 with a risk of 9%. CONCLUSIONS: After THR or TKR, DCC> 3 cm or a clinical risk score greater or equal to 4 could be used as an accurate and easy clinical test for assessing the need for further DVT screening by sonography. PMID- 22079641 TI - A 48-year-old woman with amnesia. PMID- 22079642 TI - Experience talks. PMID- 22079643 TI - What factors increase the accuracy and inter-rater reliability of the Emergency Severity Index among emergency nurses in triaging adult patients? PMID- 22079644 TI - Have fun, be safe: the start of an ED community outreach program. PMID- 22079645 TI - Assessment of stroke: a review for ED nurses. PMID- 22079646 TI - Serotonin syndrome-muscle rigidity and confusion in the older adult. PMID- 22079647 TI - Do nurses eat their young? Truth and consequences. PMID- 22079648 TI - Early detection and treatment of severe sepsis in the emergency department: identifying barriers to implementation of a protocol-based approach. AB - INTRODUCTION: Despite evidence to support efficacy of early goal-directed therapy for resuscitation of patients with severe sepsis and septic shock in the emergency department, implementation remains incomplete. To identify and address specific barriers at our institution and maximize benefits of a planned sepsis treatment initiative, a baseline assessment of knowledge, attitudes, and behaviors regarding detection and treatment of severe sepsis was performed. METHODS: An online survey was offered to nurses and physicians in the emergency department of a major urban academic medical center. The questionnaire was designed to assess (1) baseline knowledge and self-reported confidence in identification of systemic inflammatory response syndrome and sepsis; (2) current practices in treatment; (3) difficulties encountered in managing sepsis cases; (4) perceived barriers to implementation of a clinical pathway based on early quantitative resuscitation goals; and (5) to elicit suggestions for improvement of sepsis treatment within the department. RESULTS: Respondents (n = 101) identified barriers to a quantitative resuscitation protocol for sepsis. These barriers included the inability to perform central venous pressure/central venous oxygen saturation monitoring, limited physical space in the emergency department, and lack of sufficient nursing staff. Among nurses, the greatest perceived contributor to delays in treatment was a delay in diagnosis by physicians; among physicians, a delay in availability of ICU beds and nursing delays were the greatest barriers. Despite these issues, respondents indicated that a written protocol would be helpful to them. DISCUSSION: Knowledge gaps and procedural hurdles identified by the survey will inform both educational and process components of an initiative to improve sepsis care in the emergency department. PMID- 22079649 TI - The war against warfarin: evaluating current treatment guidelines for patients who have had an acute ischemic stroke and are taking warfarin. PMID- 22079650 TI - Lessons learned in developing and implementing the nurse practitioner role in an urban Canadian emergency department. PMID- 22079651 TI - Preventing downstream Clostridium difficile infections with upstream antibiotic management. AB - Clostridium difficile infection (CDI) remains a devastating cause of hospital acquired diarrhea. Treatment modalities have centered traditionally on two antibiotics, metronidazole and oral vancomycin. Both drugs, however, have been associated with variable relapse rates up to 20%. Fidaxomicin, a new oral agent with targeted C. difficile activity, may reduce the chance of relapse, but has not yet entered mainstream clinical practice. CDI is associated with significant morbidity and mortality. In the past decade, the emergence of hypervirulent strains has led to medical management failures and the increased need for surgical intervention. Control of the disease requires excellent infection prevention practices, yet can remain a difficult operational challenge. Selective pressure of antibiotic therapy can increase or lessen the risk depending on the agent used. We believe that antibiotic selection for the treatment of patients with any infectious disease must account for the possibility of subsequent severe CDI. We posit 'upstream' antibiotic selection will prevent 'downstream' CDI and potentially ameliorate deficiencies in infection prevention practices. Formal studies evaluating such an endpoint would be useful in this era of dangerous CDI. PMID- 22079652 TI - Leprosy and the natural selection for psoriasis. AB - Psoriasis is a genetically determined, almost worldwide-distributed inflammatory skin disease with overall higher prevalence among people of northern European ancestry. Since enhanced innate immunity is an important feature of the pathophysiology of this disease, it has been proposed that differences in the prevalence of psoriasis in different populations mainly result from differences in natural selection for gene polymorphisms associated with more vigorous immunity against infectious agents. However the infectious agent(s) that could have acted upon human population as selection pressure for psoriasis is still obscure. Based on the remarkable clinical observation that psoriasis and leprosy are almost mutually exclusive, a fact that is further supported by divergent HLA patterns in patients with psoriasis and leprosy we propose that "resisting leprosy" may have been the evolutionary advantage that favoured the expansion of some psoriasis-associated genotypes especially in the progenitors of modern Europeans. Moreover, we suggest that the spreading out of a certain genetic resistance trait may offer a supplementary explanation for the better understanding of the relatively rapid decline of leprosy in the late medieval epoch in Europe. Both genetic and paleoepidemiologic methods could be employed in order to challenge the present hypothesis. PMID- 22079653 TI - Extensive abnormality of brain white matter integrity in pathological gambling. AB - Several magnetic resonance imaging (MRI) studies in substance use disorders have shown brain white matter integrity abnormalities, but there are no studies in pathological gambling, a form of behavioral addiction. Our objective was to investigate possible changes in regional brain gray and white matter volumes, and axonal white matter integrity in pathological gamblers compared to healthy controls. Twenty-four subjects (12 clinically diagnosed male pathological gamblers and 12 age-matched healthy male volunteers) underwent structural and diffusion weighted brain MRI scans, which were analyzed with voxel-based morphometry and tract based spatial statistics. In pathological gamblers, widespread lower white matter integrity (lower fractional anisotropy, higher mean diffusivity) was seen in multiple brain regions including the corpus callosum, the cingulum, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the anterior limb of internal capsule, the anterior thalamic radiation, the inferior longitudinal fascicle and the uncinate/inferior fronto-occipital fascicle. There were no volumetric differences in gray or white matter between pathological gamblers and controls. The results suggest that pathological gambling is associated with extensive lower integrity of several brain white matter tracts. The diffusion abnormality closely resembles previous findings in individuals with substance addictions. PMID- 22079654 TI - Use of inverse probability weighting to adjust for non-participation in estimating brain volumes in schizophrenia patients. AB - Low participation is a potential source of bias in population-based studies. This article presents use of inverse probability weighting (IPW) in adjusting for non participation in estimation of brain volumes among subjects with schizophrenia. Altogether 101 schizophrenia subjects and 187 non-psychotic comparison subjects belonging to the Northern Finland 1966 Birth Cohort were invited to participate in a field study during 1999-2001. Volumes of grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) were compared between the 54 participating schizophrenia subjects and 100 comparison subjects. IPW by illness-related auxiliary variables did not affect the estimated GM and WM mean volumes, but increased the estimated CSF mean volume in schizophrenia subjects. When adjusted for intracranial volume and family history of psychosis, IPW led to smaller estimated GM and WM mean volumes. Especially IPW by a disability pension and a higher amount of hospitalisation due to psychosis had effect on estimated mean brain volumes. The IPW method can be used to improve estimates affected by non participation by reflecting the true differences in the target population. PMID- 22079655 TI - Short term vs. long term test-retest reproducibility of 123I-ADAM for the binding of serotonin transporters in the human brain. AB - Previous brain imaging studies have demonstrated a seasonal difference of serotonin transporter (SERT) binding in the human brain. However, the results were somewhat contradictory. We conducted test-retest study with single photon emission computed tomography (SPECT) with 123I-ADAM as ligand in 28 healthy subjects. Ten of the subjects were studied within 1 month, whereas 18 were randomly assigned to be studied over a period of up to 1 year. The primary measure was the specific uptake ratio (SUR). Regions of interest included the midbrain, thalamus, putamen and caudate. The intra-class correlation coefficient (ICC) was 0.52-0.94 across different brain regions over 1 month, whereas the ICC was -0.24-0.63 over a 1-year period. The 1-month variability ranged from 6.5 +/- 5.1% to 12.5 +/- 10.6% across different brain regions, and the 1-year variability ranged from 16.5 +/- 9.6% to 41.9 +/- 35.5%. The Kruskal-Wallis test revealed a significant difference of variability across months. The Wilcoxon Signed Ranks Test showed the SUR between test-retest scans was of borderline significance. Curve fitting, using a 4th degree polynomial model, revealed a significant circadian correlation between the variability and interval of test-retest measurements. Our findings demonstrate the test-retest reproducibility of 123I ADAM in different time periods and suggest that circadian variation of SERT levels in the human brain might exist. PMID- 22079656 TI - "I won, but I'm not getting my hopes up": depression moderates the relationship of outcomes and reward anticipation. AB - Major Depressive Disorder (MDD) in adolescents is characterized by alterations in positive emotions and reward processing. Recent investigations using functional magnetic resonance imaging (fMRI) find depression-related differences in reward anticipation. However, it is unknown whether feedback influences subsequent reward anticipation, which may highlight the context of reward processing. Ten youth with MDD and 16 youth with no history of MDD completed an fMRI assessment using a reward task. Reward anticipation was indexed by blood oxygen level dependent signal change in the striatum following winning, losing, non-winning, and non-losing outcomes. A significant interaction between diagnostic status and outcome condition predicted reward anticipation in the caudate. Decomposition of the interaction indicated that following winning outcomes, depressed youth demonstrated reduced reward anticipation relative to healthy youth. However, no significant differences between depressed and healthy youth were found after other outcomes. Reward anticipation is altered following winning outcomes. This finding has implications for understanding the developmental pathophysiology of MDD and suggests specific contexts where altered motivational system functioning may play a role in maintaining depression. PMID- 22079657 TI - Reduced prefrontal oxygenation during object and spatial visual working memory in unpolar and bipolar depression. AB - Altered prefrontal brain activity (e.g. hypofrontality) during cognitive tasks such as working memory is a core neuroimaging marker in unipolar (UNI) and bipolar (BI) depression. The present study investigated for the first time UNI (n=16) and BI patients (n=14) in a working memory task including different processes (storage and matching) and components (object and spatial visual) with functional near-infrared spectroscopy (fNIRS) over the prefrontal cortex. In healthy controls (n=15) comparable to both patient groups, changes of oxygenated and deoxygenated haemoglobin indicated increased ventro-lateral, dorso-lateral prefrontal and superior frontal cortex activity for object and spatial visual working memory storage as compared to the control condition. In contrast, both patient groups showed diminished brain activity in all working memory conditions. Results revealed unspecific deficits that did not allow the differentiation between unipolar and bipolar depression in dependence of working memory processes or components. However, fNIRS can be considered as a valid, easy manageable, low cost and rapid tool for measuring (diminished) prefrontal cortex functions. PMID- 22079658 TI - Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards. AB - Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. PMID- 22079660 TI - Neural correlates of emotional recognition memory in schizophrenia: effects of valence and arousal. AB - Schizophrenia patients are often impaired in their memory for emotional events compared with healthy subjects. Investigations of the neural correlates of emotional memory in schizophrenia patients are scarce in the literature. The present study aimed to compare cerebral activations in schizophrenia patients and healthy controls during memory retrieval of emotional images that varied in both valence and arousal. In a study with functional magnetic resonance imaging, 37 schizophrenia patients were compared with 37 healthy participants while performing a yes/no recognition paradigm with positive, negative (differing in arousal intensity) and neutral images. Schizophrenia patients performed worse than healthy controls in all experimental conditions. They showed less cerebral activation in limbic and prefrontal regions than controls during retrieval of negatively valenced stimuli, but had a similar pattern of brain activation compared with controls during retrieval of positively valenced stimuli (particularly in the high arousal condition) in the cerebellum, temporal lobe and prefrontal cortex. Both groups demonstrated increased brain activations in the high relative to low arousing conditions. Our results suggest atypical brain function during retrieval of negative pictures, but intact functional circuitry of positive affect during episodic memory retrieval in schizophrenia patients. The arousal data revealed that schizophrenia patients closely resemble the control group at both the behavioral and neurofunctional level. PMID- 22079659 TI - Default mode network dysfunction in adults with prenatal alcohol exposure. AB - Prenatal alcohol exposure (PAE) is known to cause significant cognitive and attentional dysfunction. Given the relationship between default mode network (DMN) activity and task-related attentional modulation, it is possible that PAE affects activity of this network. In the present study, task-related deactivation as well as structural and resting state functional connectivity of the DMN were examined using diffusional tensor imaging and functional magnetic resonance imaging in non-dysmorphic and dysmorphic PAE populations and compared to healthy controls. The dysmorphic PAE group was found to have reduced DMN deactivation as compared to controls, indicating poorer attentional modulation during the cognitive task. Additionally, structural connectivity and baseline functional connectivity were lower in both PAE groups as compared to controls. Primarily the findings suggest that learning problems seen with PAE may be a combination of general attentional and specific cognitive deficits. A secondary implication is that DMN activity is affected to varying extents depending on the degree of PAE. PMID- 22079661 TI - Prefrontal hyperactivation during a working memory task in early-onset schizophrenia spectrum disorders: an fMRI study. AB - Working memory (WM) dysfunction is increasingly recognized as a core feature of schizophrenia, but few studies have investigated prefrontal activation during WM tasks in early-onset schizophrenia spectrum disorder (EOS). Our aim was to explore prefrontal activation during a WM-task in EOS patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Fifteen patients with EOS and 15 matched healthy controls performed a 0-back and a 2-back task while fMRI data were acquired. Results indicated that even though performance between patients and controls was comparable on both tasks, there was a hyperactivation in patients' ventrolateral prefrontal cortex (VLPFC) during the 2-back task compared to healthy controls. This pattern of activation suggests that, in patients with EOS, the VLPFC compensated in order to match performance of the controls. The activations in the EOS group may reflect the use of a compensatory, cognitive strategy while solving WM-tasks. PMID- 22079662 TI - Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients. AB - White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) in diffusion tensor imaging (DTI) studies, but the empirical evidence about the diagnostic specificity of white matter abnormalities in these disorders is still limited. This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania. For this purpose, DTI was used to assess white matter integrity in patients with paranoid schizophrenia (n=25) and psychotic bipolar mania (n=18) who had been treated with standard pharmacotherapy for fewer than 5 days at the time of study, as well as in normal controls (n=30). The differences in FA were measured by use of voxel-based analysis. The results show that reduced FA was found in the left posterior corona radiata (PCR) in patients with psychotic bipolar mania and paranoid schizophrenia compared to the controls. Patients with psychotic bipolar mania also showed a significant reduction in FA in right posterior corona radiata and in right anterior thalamic radiation (ATR). A direct comparison between the two patient groups found no significant differences in any regions, and none of the findings were associated with illness duration. Correlation analysis indicated that FA values showed a significant negative correlation with positive symptom scores on the Positive and Negative Syndrome Scale in the left frontal-parietal lobe in the paranoid schizophrenia. It was concluded that common abnormalities in the left PCR might imply an overlap in white matter pathology in the two disorders and might be related to shared risk factors for the two disorders. PMID- 22079663 TI - Switchable fluorophores for protein labeling in living cells. AB - Numerous synthetic fluorophores have been developed that can switch their spectroscopic properties upon interaction with other molecules or by irradiation with light. In recent years, protein-labeling techniques have been introduced that permit the specific attachment of such molecules to proteins of interest in living cells. We review here how the attachment of switchable fluorophores to selected proteins of interest via self-labeling protein tags enables new applications in different areas of biology and discuss how these molecules could be further improved. PMID- 22079664 TI - Assembly of different length of polyubiquitins on the catalytic cysteine of E2 enzymes without E3 ligase; a novel application of non-reduced/reduced 2 dimensional electrophoresis. AB - In this study using non-reduced/reduced 2-dimensional electrophoresis (NR/R-2DE), we clearly demonstrated that E3-independent ubiquitination by Ube2K produced not only unanchored but also Ube2K-linked polyubiquitins through thioester and isopeptide bonds. E3-independent assembly of polyubiquitins on the catalytic cysteine of Ube2K strongly supports the possibility of 'en bloc transfer' for polyubiquitination. From the same analyses of E3-independent ubiquitination products by other E2s, we also found that different lengths of polyubiquitins were linked to different E2s through thioester bond; longer chains by Cdc34 like Ube2K, short chains by Ube2g2, and mono-ubiquitin by UbcH10. Our results suggest that E2s possess the different intrinsic catalytic activities for polyubiquitination. PMID- 22079665 TI - Following G-quadruplex formation by its intrinsic fluorescence. AB - We characterized and compared the fluorescence properties of various well-defined G-quadruplex structures. The increase of intrinsic fluorescence of G-rich DNA sequences when they form G-quadruplexes can be used to monitor the folding and unfolding of G-quadruplexes as a function of cations and temperature. The temperature-dependent fluorescence spectra of different G-quadruplexes also exhibit characteristic patterns. Thus, the stability and possibly also the structure of G-quadruplexes can be characterized and distinguished by their intrinsic fluorescence spectra. PMID- 22079666 TI - Hydrophobic residues of terminal protein domain of hepatitis B virus polymerase contribute to distinct steps in viral genome replication. AB - Hepatitis B virus (HBV) replicates its DNA genome via reverse transcription. Precise roles of the terminal protein domain of HBV polymerase remain unknown. To gain insight, we created alanine substitution mutations at hydrophobic residues (i.e., tyrosine, tryptophan, and isoleucine), and then examined the extent by which these mutants carry out viral genome replication. Evidence indicated that three hydrophobic residues of the terminal protein domain (i.e., W74, Y147, and Y173) contribute to distinct steps of viral genome replication: the former two residues are important for viral DNA synthesis, while the latter is important for viral RNA encapsidation. PMID- 22079667 TI - Functional interaction between purinergic receptors: effect of ligands for A2A and P2Y12 receptors on P2Y1 receptor function. AB - A(2A) adenosine receptor (A(2A)R), P2Y(1) receptor (P2Y(1)R) and P2Y(12) receptor (P2Y(12)R) are predominantly expressed on human platelets. The individual role of each of these receptors in platelet aggregation has been actively reported. Previously, hetero-oligomerization between these three receptors has been shown to occur. Here, we show that Ca(2+) signaling evoked by the P2Y(1)R agonist, 2 methylthioladenosine 5' diphosphate (2MeSADP) was significantly inhibited by the A(2A)R antagonist (ZM241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3 alpha][1,3,5]triazin-5-yl amino]ethyl) phenol) and SCH442416) and the P2Y(12)R antagonist (ARC69931MX) (N6-(2-methyl-thioethyl)-2-(3,3,3-trifluoropropylthio) beta,gamma-dichloromethylene-ATP)) using HEK293T cells expressing the three receptors. It was confirmed that inhibition of P2Y(1)R signaling by A(2A)R and P2Y(12)R antagonists was indeed mediated through A(2A)R and P2Y(12)R using 1321N1 human astrocytoma cells which do not express P2Y receptors. We expect that intermolecular signal transduction and specific conformational changes occur among components of hetero-oligomers formed by these three receptors. PMID- 22079669 TI - Top-down control in a patchy environment: revisiting the stabilizing role of food dependent predator dispersal. AB - In this paper, we revisit the stabilizing role that predator dispersal and aggregation have in the top-down regulation of predator-prey systems in a heterogeneous environment. We consider an environment consisting of sites interconnected by dispersal, and propose a novel mechanism of stabilization for the case with a non-sigmoid functional response of predators. We assume that the carrying capacity of the prey is infinitely large in each site, and show that successful top-down regulation of this otherwise globally unstable system is made possible through an interplay between the unevenness of prey fitness across the sites and the rapid food-dependent migration of predators. We argue that this mechanism of stabilization is different from those previously reported in the literature: in particular, it requires a high degree of synchronicity in local oscillations of species densities across the sites. Prey outbreaks take place synchronously, but the unevenness of prey growth rates across the sites results in a pronounced difference in the species densities, and so the predator quickly disperses to the sites with the highest prey abundances. For this reason, the consumption of prey mostly takes place in the sites with high densities of prey, which assures an efficient suppression of outbreaks. Furthermore, when the total size of prey population is low, the distribution of both species among the sites becomes more even, and this prevents overconsumption of the prey by the predator. Finally, we put forward the hypothesis that this mechanism, when considered in a tri-trophic plankton community in the water column, can explain the stability of the nutrient-rich low-chlorophyll open ocean regions. PMID- 22079668 TI - Superoxide dismutases: ancient enzymes and new insights. AB - Superoxide dismutases (SODs) catalyze the de toxification of superoxide. SODs therefore acquired great importance as O(2) became prevalent following the evolution of oxygenic photosynthesis. Thus the three forms of SOD provide intriguing insights into the evolution of the organisms and organelles that carry them today. Although ancient organisms employed Fe-dependent SODs, oxidation of the environment made Fe less bio-available, and more dangerous. Indeed, modern lineages make greater use of homologous Mn-dependent SODs. Our studies on the Fe substituted MnSOD of Escherichia coli, as well as redox tuning in the FeSOD of E. coli shed light on how evolution accommodated differences between Fe and Mn that would affect SOD performance, in SOD proteins whose activity is specific to one or other metal ion. PMID- 22079670 TI - Evolutionary jumping and breakthrough in tree masting evolution. AB - Many long-lived plants such as trees show masting or intermittent and synchronized reproduction. In a coupled chaos system describing the dynamics of individual-plant resource budgets, masting occurs when the resource depletion coefficient k (ratio of the reproductive expenditure to the excess resource reserve) is large. Here, we mathematically studied the condition for masting evolution. In an infinitely large population, we obtained a deterministic dynamical system, to which we applied the pairwise invasibility plot and convergence stability of evolutionary singularity analyses. We prove that plants reproducing at the same rate every year are not evolutionarily stable. The resource depletion coefficient k increases, and the system oscillates with a period of 2 years (high and low reproduction) if k<1. Alternatively, k may evolve further and jump to a value >1, resulting in the sudden start of intermittent reproduction. We confirm that a high survivorship of young plants (seedlings) in the light-limited understory favors masting evolution, as previously suggested by computer simulations and field observations. The stochasticity caused by the finiteness of population size also promotes masting evolution. PMID- 22079672 TI - Increased Y-chromosome resolution of haplogroup O suggests genetic ties between the Ami aborigines of Taiwan and the Polynesian Islands of Samoa and Tonga. AB - The Austronesian expansion has left its fingerprint throughout two thirds of the circumference of the globe reaching the island of Madagascar in East Africa to the west and Easter Island, off the coast of Chile, to the east. To date, several theories exist to explain the current genetic distribution of Austronesian populations, with the "slow boat" model being the most widely accepted, though other conjectures (i.e., the "express train" and "entangled bank" hypotheses) have also been widely discussed. In the current study, 158 Y chromosomes from the Polynesian archipelagos of Samoa and Tonga were typed using high resolution binary markers and compared to populations across Mainland East Asia, Taiwan, Island Southeast Asia, Melanesia and Polynesia in order to establish their patrilineal genetic relationships. Y-STR haplotypes on the C2 (M38), C2a (M208), O1a (M119), O3 (M122) and O3a2 (P201) backgrounds were utilized in an attempt to identify the differing sources of the current Y-chromosomal haplogroups present throughout Polynesia (of Melanesian and/or Asian descent). We find that, while haplogroups C2a, S and K3-P79 suggest a Melanesian component in 23%-42% of the Samoan and Tongan Y chromosomes, the majority of the paternal Polynesian gene pool exhibits ties to East Asia. In particular, the prominence of sub-haplogroup O3a2c* (P164), which has previously been observed at only minimal levels in Mainland East Asians (2.0-4.5%), in both Polynesians (ranging from 19% in Manua to 54% in Tonga) and Ami aborigines from Taiwan (37%) provides, for the first time, evidence for a genetic connection between the Polynesian populations and the Ami. PMID- 22079671 TI - GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum. AB - Glucose-regulated protein 94 is the HSP90-like protein in the lumen of the endoplasmic reticulum and therefore it chaperones secreted and membrane proteins. It has essential functions in development and physiology of multicellular organisms, at least in part because of this unique clientele. GRP94 shares many biochemical features with other HSP90 proteins, in particular its domain structure and ATPase activity, but also displays distinct activities, such as calcium binding, necessitated by the conditions in the endoplasmic reticulum. GRP94's mode of action varies from the general HSP90 theme in the conformational changes induced by nucleotide binding, and in its interactions with co chaperones, which are very different from known cytosolic co-chaperones. GRP94 is more selective than many of the ER chaperones and the basis for this selectivity remains obscure. Recent development of molecular tools and functional assays has expanded the spectrum of clients that rely on GRP94 activity, but it is still not clear how the chaperone binds them, or what aspect of folding it impacts. These mechanistic questions and the regulation of GRP94 activity by other proteins and by post-translational modification differences pose new questions and present future research avenues. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). PMID- 22079673 TI - The forms and functions of peer social support for people living with HIV. AB - Peers may be important sources of coping assistance, but their impact can be better understood if we examine their influence across various contexts. Although social support studies focused on people living with HIV have examined peer support in various contexts, they do not comprehensively account for situations in which peer support might be provided. The specific aims of this study were to (a) describe the various forms and functions of peer support for people living with HIV and (b) validate the Dennis (2003) concept analysis of peer support within health contexts. Results indicate that peer support is a potentially important adjunct to clinical care for enhancing coping skills, thereby improving the psychosocial functioning of people living with HIV. It is important to (a) assess patient access to peer support, (b) provide opportunities for peer support in the clinical setting, and (c) enhance disclosure and support-seeking skills to facilitate this benefit. PMID- 22079674 TI - A qualitative description of women's HIV self-management techniques: context, strategies, and considerations. AB - Women living with HIV face unique challenges managing their disease. The purpose of this descriptive qualitative study was to describe self-management techniques reported by 48 women living with HIV in the United States. Participants were involved in one 90-minute, digitally recorded focus group exploring aspects of HIV self-management strategies. Descriptive statistics, qualitative description, and content analysis were used to analyze the data. Participants had been living with HIV for an average of 12 years, and most (69%) were engaged in routine HIV care (85%) and were currently receiving antiretroviral therapy. Participants reported using self-management techniques: taking personal time (n = 23; 48%), advocacy (n = 12; 25%), sleeping (n = 17, 35%), attending support groups (n = 10; 21%), and attending medical appointments (n = 8; 17%). Nurses can add strategies to enhance HIV self-management to routine clinical care, which may have a positive impact on the health of women living with HIV. PMID- 22079675 TI - Parental support and condom use among transgender female youth. AB - Evidence suggests that transgender female youth (TFY), much like their adult transgender female peers, are at high risk for HIV. Yet little attention has been given to important developmental experiences of TFY that may impact HIV risk for this youth population. The overall purpose of this study was to explore HIV risk in TFY. A reoccurring theme from the qualitative data was the importance of parents. To better understand the impact of parents on HIV risk among TFY, in depth individual interview data from 21 TFY in Los Angeles and Chicago were analyzed, suggesting a potential link between HIV-related risk behavior and parental support. Youth with parental support in this sample reported regular condom use, while those without such support reported inconsistent condom use. Implications for the unique research and interventions needs of TFY related to parental support and sexual risk behaviors are discussed. PMID- 22079676 TI - Response to commentary by P.H. Noh. PMID- 22079677 TI - Hematological malignancy associated with polymyositis and dermatomyositis. AB - The aims of this present study were to: 1) assess the characteristics of hematological malignancies in polymyositis/polymyositis (PM/DM) patients; and 2) determine predictive variables of hematological malignancies in PM/DM patients. We retrospectively reviewed the medical records of 32 patients (14 PM, 18 DM) associated with hematological malignancies. In our 32 PM/DM patients, hematological malignancy was concurrently identified (18.8%) or occurred during the course of PM/DM (31.2%); although, PM/DM more often preceded hematological malignancy onset (50%). We observed that the types of hematological malignancies varied, consisting of: B-cell lymphoma (n=20), T-cell lymphoma (n=4), Hodgkin's disease (n=2), multiple myeloma (n=1), myelodysplastic syndrome without excess of blasts (n=3), hairy cell (n=1) and acute lymphocytic leukemia (n=1). In 21 patients of our 32 patients with PM/DM-associated hematological malignancy (65.6% of cases), PM/DM paralleled the course of hematological malignancy. Finally, we observed that patients with PM/DM-associated hematological malignancies had a poor prognosis, the survival status ranging from 96.9%, 78.1% and 51.4% at 1, 3 and 5years, respectively. Interestingly, we found that patients with hematological malignancies, compared with those without were older and more frequently had DM; on the other hand, these patients less commonly exhibited: joint involvement (p=0.017), interstitial lung disease (p=0.06) and anti-Jo1 antibody (p=0.001). Taken together, our study underscores that the association between PM/DM and hematological malignancy, especially lymphoma, should not be ignored. Our findings also suggest that antisynthetase syndrome may be a protective factor of hematological malignancy in PM/DM patients. PMID- 22079678 TI - Predictors of resolution of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma in premenopausal women treated with progestin therapy. AB - OBJECTIVE: To identify clinical and pathologic predictors of response to progestin treatment in premenopausal women with complex atypical hyperplasia (CAH) and Grade 1 endometrial adenocarcinoma (Grade 1 EA). METHODS: Forty premenopausal patients with Grade 1 EA or CAH who underwent progestin therapy for a minimum of 8 weeks were retrospectively identified. Patient characteristics and histopathologic features of pretreatment and first follow-up endometrial specimens were evaluated as predictors of resolution, defined as absence of hyperplasia or carcinoma. RESULTS: Kaplan-Meier analysis indicated 63% resolution at 18 months of follow-up. Multivariate classification analysis showed that resolution rates were higher in individuals with a low pre-treatment qualitative abnormal architecture score and a BMI <35 (Standardized Resolution Ratio (SRR)=1.48, p=0.03). The diagnosis of benign endometrium or simple hyperplasia on the first follow-up specimen was highly predictive of resolution (SRR=2.25, p=0.002). Resolution rates were lower among subjects with a high pre-treatment qualitative abnormal architecture score (SRR=0.37, p<0.03) and lowest in subjects whose first follow-up specimen showed persistent complexity, atypia, or carcinoma with adjacent stromal decidualization (SRR=0.24, p=0.002). CONCLUSIONS: Clinical and pathologic parameters can predict response to progestin therapy in premenopausal women with CAH and Grade 1 EA. A low likelihood of resolution is predicted by an unfavorable pre-treatment architectural score and lack of pathological response in the first specimen, despite adjacent stromal decidualization. PMID- 22079679 TI - Robotic-assisted surgery in gynecologic oncology: a Society of Gynecologic Oncology consensus statement. Developed by the Society of Gynecologic Oncology's Clinical Practice Robotics Task Force. PMID- 22079680 TI - Autoimmune disease and gender: plausible mechanisms for the female predominance of autoimmunity. AB - A large number of autoimmune diseases (ADs) are more prevalent in women. The more frequent the AD and the later it appears, the more women are affected. Many ideas mainly based on hormonal and genetic factors that influence the autoimmune systems of females and males differently, have been proposed to explain this predominance. These hypotheses have gained credence mostly because many of these diseases appear or fluctuate when there are hormonal changes such as in late adolescence and pregnancy. Differences in X chromosome characteristics between men and women with an AD have led researchers to think that the genetic background of this group of diseases also relates to the genetic determinants of gender. These hormonal changes as well as the genetic factors that could explain why women are more prone to develop ADs are herein reviewed. PMID- 22079681 TI - Sequential osteoporosis treatments. AB - Osteoporosis is a major public health concern due both to its high prevalence and to its association with potentially serious fractures. The chronic nature of osteoporosis, together with the aging of the population, may result in a need for prolonged treatment consisting in the sequential use of several osteoporosis drugs. Situations in which switching from one osteoporosis drug to another may be considered include the occurrence of a fracture despite treatment, poor treatment adherence, side effects, and completion of a first-line treatment course. The available recommendations for postmenopausal women deal only with the indications for first-line osteoporosis treatment. Studies on drug sequences used an open label design and failed to collect data on fractures. Thus, there is no scientific evidence supporting a specific treatment sequence, the only exception being teriparatide followed by a bone resorption inhibitor. Consequently, selection of the second drug in an osteoporotic woman is a matter of clinical judgment, which can be guided by several factors such as health insurance reimbursement restrictions, characteristics of the osteoporosis (e.g., severity and whether there is a predominant risk of peripheral fractures), co-morbidities, contraindications to specific drugs, and patient adherence to prescriptions. PMID- 22079682 TI - Bird schistosomes in planorbid snails in the Czech Republic. AB - Bird schistosomes have been in focus as causative agents of cercarial dermatitis of humans in the last years; however, our knowledge of their species spectrum and intermediate host specificity is still insufficient. Our study focused on bird schistosomes developing in planorbid snails that have been less studied so far. From 2001 to 2010, cercariae of bird schistosomes were found in four snail species (Gyraulus albus, Segmentina nitida, Anisus vortex and Planorbis planorbis) from seven localities in the Czech Republic. Based on morphology and results of molecular analysis, the isolates found belong to at least six species. Five of them are probably undescribed species, and one species appears to be identical with Gigantobilharzia vittensis Reimer, 1963 (syn. G. suebica Donges, 1964). The finding from S. nitida represents the first report of a bird schistosome from this snail. PMID- 22079683 TI - IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. AB - INTRODUCTION: Diabetes is an increasingly important condition globally and robust estimates of its prevalence are required for allocating resources. METHODS: Data sources from 1980 to April 2011 were sought and characterised. The Analytic Hierarchy Process (AHP) was used to select the most appropriate study or studies for each country, and estimates for countries without data were modelled. A logistic regression model was used to generate smoothed age-specific estimates which were applied to UN population estimates for 2011. RESULTS: A total of 565 data sources were reviewed, of which 170 sources from 110 countries were selected. In 2011 there are 366 million people with diabetes, and this is expected to rise to 552 million by 2030. Most people with diabetes live in low- and middle-income countries, and these countries will also see the greatest increase over the next 19 years. DISCUSSION: This paper builds on previous IDF estimates and shows that the global diabetes epidemic continues to grow. Recent studies show that previous estimates have been very conservative. The new IDF estimates use a simple and transparent approach and are consistent with recent estimates from the Global Burden of Disease study. IDF estimates will be updated annually. PMID- 22079684 TI - Asyntactic comprehension, working memory, and acute ischemia in Broca's area versus angular gyrus. AB - We evaluated sentence comprehension of variety of sentence constructions and components of short-term memory (STM) in 53 individuals with acute ischemic stroke, to test some current hypotheses about the role of Broca's area in these tasks. We found that some patients show structure-specific, task-independent deficits in sentence comprehension, with chance level of accuracy on passive reversible sentences, more impaired comprehension of object-cleft than subject cleft sentences, and more impaired comprehension of reversible than irreversible sentences in both sentence-picture matching and enactment tasks. In a dichotomous analysis, this pattern of "asyntactic comprehension" was associated with dysfunctional tissue in left angular gyrus, rather than dysfunctional tissue in Broca's area as previously proposed. Tissue dysfunction in left Brodmann area (BA) 44, part of Broca's area, was associated with phonological STM impairment defined by forward digit span<=4. Verbal working memory (VWM) defined by backward digit span<=2 was associated with tissue dysfunction left premotor cortex (BA 6). In a continuous analysis, patients with acute ischemia in left BA 44 were impaired in phonological STM. Patients with ischemia in left BA 45 and BA 6 were impaired in passive, reversible sentences, STM, and VWM. Patients with ischemia in left BA 39 were impaired in passive reversible sentences, object-cleft sentences, STM, and VWM. Therefore, various components of working memory seem to depend on a network of brain regions that include left angular gyrus and posterior frontal cortex (BA 6, 44, 45); left BA 45 and angular gyrus (BA 39) may have additional roles in comprehension of syntax such as thematic role checking. PMID- 22079685 TI - The role of oxidized phospholipids, lipoprotein (a) and biomarkers of oxidized lipoproteins in chronically occluded coronary arteries in sudden cardiac death and following successful percutaneous revascularization. AB - AIMS: OxPL are pro-inflammatory and may mediate atherogenesis, thrombosis and endothelial dysfunction. We studied the histological presence and temporal increases in oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB), lipoprotein (a) [Lp(a)] and biomarkers of oxidized lipoproteins in subjects with chronic total coronary occlusions (CTO) with sudden cardiac death (SCD) and following percutaneous coronary intervention (PCI). METHODS: Eight subjects with SCD and CTO and 33 patients with successful PCI of CTO were included. Blood samples were drawn before PCI, immediately post-PCI, at 6 and 24 h, at 3 days and at 1 week. Plasma levels of OxPL/apoB, Lp(a), IgG and IgM autoantibodies to malondialdehyde (MDA) low-density lipoprotein and apoB-immune complexes were measured in all samples and compared with previous data from 141 patients undergoing PCI of non-CTO vessels. RESULTS: Immunohistochemistry of coronary CTOs revealed OxPL and MDA-like epitopes, particularly in areas of recanalized and organized thrombus and neovascularization. Following PCI, OxPL/apoB and Lp(a) levels, expressed as percent change from baseline levels before PCI, rose gradually and progressively over the next 7 days. In contrast, levels of OxPL/apoB and Lp(a) in non-CTO vessels rose immediately post PCI and then dropped rapidly to baseline within 24 h. CONCLUSIONS: CTOs contain immunohistological evidence of OxPL and MDA-like epitopes. Successful PCI of CTOs results in a slower increase in OxPL/apoB and Lp(a) but higher increase in IgM immune complexes compared to non-CTO vessels. Pro-inflammatory oxidation-specific epitopes may impact development of CTOs and affect outcomes following PCI that can be evaluated in larger clinical trials. PMID- 22079686 TI - Growth of the microalgae Neochloris oleoabundans at high partial oxygen pressures and sub-saturating light intensity. AB - The effect of partial oxygen pressure on growth of Neochloris oleoabundans was studied at sub-saturating light intensity in a fully-controlled stirred tank photobioreactor. At the three partial oxygen pressures tested (P(O)2= 0.24; 0.63; 0.84 bar), the specific growth rate was 1.38; 1.36 and 1.06 day(-1), respectively. An increase of the P(CO)2from 0.007 to 0.02 bar at P(O2) of 0.84 bar resulted in an increase in the growth rate from 1.06 to 1.36 day(-1). These results confirm that the reduction of algal growth at high oxygen concentrations at sub-saturating light conditions is mainly caused by competitive inhibition of Rubisco. This negative effect on growth can be overcome by restoring the O(2)/CO(2) ratio by an increase in the partial carbon dioxide pressure. In comparison to general practice (P(O(2)) = 0.42 bar), working at partial O(2) pressure of 0.84 bar could reduce the energy requirement for degassing by a factor of 3-4. PMID- 22079687 TI - Assessing the environmental impact of biobleaching: effects of the operational conditions. AB - The environmental impact of enzyme bleaching stages applied to oxygen-delignified eucalypt kraft pulp was assessed via the chemical oxygen demand (COD), color, absorbance spectrum, residual enzyme activity and Microtox toxicity of the effluents from a laccase-HBT (1-hydoxybenzotriazole) treatment. The influence of the laccase and HBT doses, and reaction time, on these effluent properties was also examined. The laccase dose was found to be the individual variable most strongly affecting COD, whereas the oxidized form of HBT was the main source of increased color and toxicity in the effluents. Moreover, it inactivated the enzyme. Oxidation of the mediator was very fast and essentially dependent on the laccase dose. Using the laccase-mediator treatment after a xylanase stage improved pulp properties without affecting effluent properties. This result holds great promise with a view to the industrial implementation of biobleaching sequences involving the two enzymes in the future. PMID- 22079688 TI - Activation of lignocellulosic biomass by ionic liquid for biorefinery fractionation. AB - Fractionation of lignocellulosic biomass is an attractive solution to develop an economically viable biorefinery by providing a saccharide fraction to produce fuels and a lignin stream that can be converted into high value products such as carbon fibers. In this study, the analysis of ionic liquid-activated biomass demonstrates that in addition of decreasing crystallinity, the selected ILs (1 butyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium chloride and 1 ethyl-3-methylimidazolium acetate) deacetylate Yellow poplar under mild conditions (dissolution at 60-80 degrees C), and lower the degradation temperature of each biomass polymeric component, thereby reducing the recalcitrance of biomass. Among the three tested ILs, 1-ethyl-3-methylimidazolium acetate performed the best, providing a strong linear relationship between the level of deacetylation and the rate of enzymatic saccharification for Yellow poplar. PMID- 22079689 TI - Acetate and propionate impact on the methanogenesis of landfill leachate and the reduction of clogging components. AB - Synthetic leachate with different initial concentrations of acetate (500-2500 mg HAc/L) and propionate (500-3500 mg HPr/L) was treated with active biomass acclimated to landfill leachate under anaerobic mesophilic conditions for 72 h. Methanogenesis was observed within all samples during the first 48 h. The greatest removal of acetate (80-100%) and propionate (15-35%) was achieved in tests with initial concentrations ranging from 1500 to 190 0mg HAc/L and from 1000 to 1800mgHPr/L. Concurrent with the removal of acids, pH increased between 0.3 and 0.45 units, to above the threshold pH for precipitation of CaCO(3). Therefore, some 50-70% of dissolved Ca(2+) was removed from solution. This study suggests that by using an equalization tank (prior to the anaerobic digester) to maintain the acetate and propionate concentrations to within their optimum range would help to alleviate clogging through the removal of dissolved Ca(2+) and maximizing CH(4) production. PMID- 22079690 TI - Efficient transposition of IS204-derived plasmids in Streptomyces coelicolor. AB - In order to study functional gene expression in Streptomyces coelicolor, a mini transposon encoding the apramycin resistance gene aac(3)IV within its inverted repeat (IR) boundaries was constructed based on IS204, which was previously identified in the genome of Nocardia asteroides YP21. The mini-transposon and IS204 transposase gene were then put on a kanamycin-resistant conjugative plasmid pDZY101 that can only replicate in Escherichia coli. After mating with S. coelicolor A3(2) M145, resistant colonies arose efficiently on both apramycin and kanamycin plates. Plasmid rescue indicated that entire plasmids were inserted into the M145 genome with cleavage at an inverted repeat junction formed by the right inverted repeat (IRR) and the last 18bp of the transposase gene, while the left inverted repeat (IRL) was untouched. Southern blot analysis of the mutants using an aac(3)IV gene probe showed that transposition of plasmid pDZY101 was genetically stable, with a single-copy insertion within the S. coelicolor M145 genome. Several mutagenesis libraries of S. coelicolor M145 were constructed using plasmid pDZY101 derivatives and the transposon insertion site was determined. The correlation between novel mutant phenotypes and previously uncharacterized genes was established and these transposon locations were widely scattered around the genome. PMID- 22079691 TI - Full and surface tibial cementation in total knee arthroplasty: a biomechanical investigation of stress distribution and remodeling in the tibia. AB - BACKGROUND: Aseptic tibial component loosening remains a major cause of total knee arthroplasty failure. The cementation technique used to achieve fixation may play a major role in loosening. Despite this, the optimum technique remains unanswered. This study aims to investigate stress and strain distributions in the proximal tibia for full cementation and surface cementation of the Genesis II tibial component. METHODS: Principal cortical bone strains were measured experimentally in intact, surface cemented and fully cemented synthetic tibiae using strain gauges. Both axial and 15 degrees flexion loading were considered. Finite element models were used to assess both cortical and cancellous bone stresses and strains. Using a bone remodeling algorithm potential sites of bone formation and resorption were identified post-implantation. FINDINGS: Principal cortical bone strain results demonstrate strong correlations between the experimental and finite element analyses (R(2)>=0.81, RMSE(%)<=17.5%). Higher cortical strains are measured for surface cementation, as full cementation creates a stiffer proximal tibial structure. Simulations reveal that both cementation techniques result in lower cancellous stresses under the baseplate compared to the intact tibia, with greater reductions being computed for full cementation. The surface cementation model displays the closest cancellous stress distribution to the intact model. In addition, bone remodeling simulations predict more extensive bone resorption under the baseplate for full cementation (43%) than for surface cementation (29%). INTERPRETATION: Full cementation results in greater stress reduction under the tibial baseplate than surface cementation, suggesting that surface cementation will result in less proximal bone resorption, thus reducing the possibility of aseptic loosening. PMID- 22079692 TI - Plasmodium falciparum MLH is schizont stage specific endonuclease. AB - Malaria is one of the most important infectious diseases in many regions around the world including India. Plasmodium falciparum is the cause of most lethal form of malaria while Plasmodium vivax is the major cause outside Africa. Regardless of considerable efforts over the last many years there is still no commercial vaccine against malaria and the disease is mainly treated using a range of established drugs. With time, the malaria parasite is developing drug resistance to most of the commonly used drugs. This drug resistance might be due to defective mismatch repair in the parasite. Previously we have reported that the P. falciparum genome contains homologues to most of the components of mismatch repair (MMR) complex. In the present study we report the detailed biochemical characterization of one of the main component of MMR complex, MLH, from P. falciparum. Our results show that MLH is an ATPase and it can incise covalently closed circular DNA in the presence of Mn(2+) or Mg(2+) ions. Using the truncated derivatives we show that full length protein MLH is required for all the enzymatic activities. Using immunodepletion assays we further show that the ATPase and endomuclease activities are attributable to PfMLH protein. Using immunofluorescence assay we report that the peak expression of MLH in both 3D7 and Dd2 strains of P. falciparum is mainly in the schizont stages of the intraerythrocytic development, where DNA replication is active. MMR also contributes to the overall fidelity of DNA replication and the peak expression of MLH in the schizont stages suggests that MLH is most likely involved in correcting the mismatches occurring during replication. This study should make a significant contribution in our better understanding of DNA metabolic processes in the parasite. PMID- 22079693 TI - EB-virus associated primary CD30-positive lymphoproliferative disease of the maxillary gingival in an immunocompetent woman. PMID- 22079694 TI - Progressive tarsal patterning in the Drosophila by temporally dynamic regulation of transcription factor genes. AB - The morphology of insect appendages, such as the number and proportion of leg tarsal segments, is immensely diverse. In Drosophila melanogaster, adult legs have five tarsal segments. Accumulating evidence indicates that tarsal segments are formed progressively through dynamic changes in the expression of transcription factor genes, such as Bar genes, during development. In this study, to examine further the basis of progressive tarsal patterning, the precise expression pattern and function of several transcription factor genes were investigated in relation to the temporal regulation of Bar expression. The results indicate that nubbin is expressed over a broad region at early stages but gradually disappears from the middle of the tarsal region. This causes the progressive expansion of rotund expression, which in turn progressively represses Bar expression, leading to the formation of the tarsal segment 3. The region corresponding to the tarsal segment 4 is formed when apterous expression is initiated, which renders Bar expression refractory to rotund. In addition, the tarsal segment 2 appears to be derived from the region that expresses Bar at a very early stage. Cessation of Bar expression in this region requires the function of spineless, which also regulates rotund expression. These findings indicate that the temporally dynamic regulatory interaction of these transcription factor genes is the fundamental basis of the progressive patterning of the tarsal region. PMID- 22079695 TI - Human hypoblast formation is not dependent on FGF signalling. AB - Mouse embryos segregate three different lineages during preimplantation development: trophoblast, epiblast and hypoblast. These differentiation processes are associated with restricted expression of key transcription factors (Cdx2, Oct4, Nanog and Gata6). The mechanisms of segregation have been extensively studied in the mouse, but are not as well characterised in other species. In the human embryo, hypoblast differentiation has not previously been characterised. Here we demonstrate co-exclusive immunolocalisation of Nanog and Gata4 in human blastocysts, implying segregation of epiblast and hypoblast, as in rodent embryos. However, the formation of hypoblast in the human is apparently not dependent upon FGF signalling, in contrast to rodent embryos. Nonetheless, the persistence of Nanog-positive cells in embryos following treatment with FGF inhibitors is suggestive of a transient naive pluripotent population in the human blastocyst, which may be similar to rodent epiblast and ES cells but is not sustained during conventional human ES cell derivation protocols. PMID- 22079696 TI - Evaluation of impact of Herba Erigerontis injection, a Chinese herbal prescription, on rat hepatic cytochrome P450 enzymes by cocktail probe drugs. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Herba Erigerontis injection (HEI), one of the most popular herbal prescription in China, is made from the aqueous extracts of Erigeron breviscapus whole plant. Now HEI is widely used for the treatment of cardiovascular diseases and cerebrovascular diseases such as coronary heart disease, anginapectoris and paralysis. AIM OF THE STUDY: The purpose of this study was to investigate the in vivo effect of HEI on rat cytochrome P450 enzymes (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2) to assess its safety through its potential to interact with co-administered drugs. MATERIALS AND METHODS: Rats were randomly divided into five groups. Rats were intravenous administrated with HEI via the caudal vein at the dosage of 1.8ml/kg or 7.2ml/kg once daily for consecutive 3 days or 14 days. On the fourth or the fifteenth day, a cocktail solution at a dose of 5ml/kg, which contained caffeine (2.5mg/kg), tolbutamide (2.5mg/kg), chlorzoxazone (5mg/kg), midazolam (5mg/kg) and metoprolol (10mg/kg), was injected via the lingual vein to all rats. Then 0.8ml blood samples were collected at a set of time-points. The plasma concentrations of probe drugs were simultaneously determined by HPLC. Pharmacokinetic parameters simulated by DAS software were used for the evaluation of HEI on the activities of rat CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2 enzymes. ANOVA and Dunnett's test was used for data analysis. RESULTS: There were no significant influence of pharmacokinetic parameters of caffeine, tolbutamide and chlorzoxazone in HEI pretreated rats. But many pharmacokinetic parameters of metoprolol and midazolam in HEI pretreated rats were affected significantly (P<0.05), which indicated that metabolism of metoprolol and midazolam in these treatment groups was evidently slowed down. CONCLUSIONS: The results from the present in vivo study suggested that HEI showed no effects on rat CYP1A2, CYP2C11 and CYP2E1, however, it demonstrated potential inhibitory effects on rat CYP2D4 and CYP3A2. Therefore, caution is needed when HEI is co-administered with drugs metabolized by human CYP2D6 or CYP3A4 in clinic, which may result in increased concentrations of these drugs and relevant herb-drug interactions. PMID- 22079697 TI - Wet or dry bandages for plaster back-slabs? AB - Cotton crepe and stretch bandages are commonly used in back-slabs and casts in orthopaedic practice. In theory they allow swelling to occur after injury while splinting the fracture. The application of a wet bandage prevents the Plaster-of Paris (POP) setting too rapidly, giving time to apply a mould or attain correct limb position. However, we hypothesised that a wet bandage contracts upon drying and may cause constriction of the splint. This study aimed at determining whether there was any significant change in length of commonly used bandages when wet as well as any further change when left to dry again. Two types of bandage were evaluated. 250 mm strips of bandage were dipped into water, gently squeezed and laid flat on a bench. The bandage was then immediately measured in length. The strips were then left to dry and re-measured. This experimental study shows that both cotton crepe and cling significantly shrink by around 7% when wet. This phenomenon has the potential to significantly increase the pressure exerted on the limb by a back-slab. We speculate that the application of wet bandages is why some back-slabs may need released. It is therefore recommended that bandages should be applied only in the dry form. PMID- 22079698 TI - Peptide derived from Pvfp-1 as bioadhesive on bio-inert surface. AB - Surface property is one important characteristic of materials, especially for ones that are bio-inert but designed for bio-medical application. In this study, we designed a series of peptides and compared their capacities as bioadhesive to improve the surface bioactivity of bio-inert material. The peptides were designed according to the sequence of Perna viridis foot protein 1 (Pvfp-1), one of the Mfp-1s (mussel foot protein 1) which play key roles in wet adhesion of mussel byssus. And the Teflon (PTFE) was chosen as a model of bio-inert material. With adsorption, adhesion and coating analysis, it was found that peptide C2 (M) (derived from the non-repeating region of Pvfp-1, contains modified DOPA) has superior coating and adhesion abilities especially on the bio-inert surface of PTFE. After coating with peptide C2 (M), the cell adhesion and spreading of osteoblast MC3T3-E1 cells on PTFE were significantly improved compared with those on non-coated surface, and the peptide-coating did not show any cell toxicity. Therefore, peptide C2 (M) is effective for improving the bioactivity of bio-inert PTFE, and could be potentially used as a bioadhesive on other bio-inert materials for biomedical application. Moreover, this study also provided new insights in designing other peptide-based bioadhesive materials. PMID- 22079700 TI - Physical and rehabilitation medicine (PRM) care pathways: "patients after knee ligament surgery". AB - This document is part of a series of documents designed by the French Physical and Rehabilitation Medicine Society (Sofmer) and the French Federation of PRM (Fedmer). These documents describe the needs for or a specific type of patients; PRM care objectives, human and material resources to be implemented, chronology as well as expected outcomes. "Care pathways in PRM" is a short document designed to enable the reader (physicians, decision-maker, administrator, lawyer or finance manager) to quickly apprehend the needs of these patients and the available therapeutic care structures for proper organization and pricing of these activities. Patients after knee ligament surgery are classified into four care sequences and two clinical categories, taking into account personal and environmental factors that could influence patients' needs, in accordance with the International Classification of Functioning (WHO). PMID- 22079701 TI - Age-dependent competition of porcine enterotoxigenic E. coli (ETEC) with different fimbria genes - short communication. AB - To investigate the association of pathogenic Escherichia coli fimbrial adhesins with the development of diarrhoea in piglets of different age groups and to test their relative competitiveness, piglets were orally inoculated with a mixture of E. coli strains harbouring F4, F5, F6, F18 and F41 fimbrial genes. A total of 537 E. coli strains with haemolytic activity were isolated from 36 diarrhoeic piglets. The F4 fimbrial gene was observed in 98.5%, 97.6% and 80.6% strains carrying fimbrial genes isolated from diarrhoeic piglets that were infected at 1, 3 and 5 weeks of age, respectively. These data demonstrate that F4 fimbriae are highly associated with diarrhoea in piglets of all age groups. Interestingly, the F18 fimbrial gene was observed in 2.4% and 25.4% strains carrying fimbrial genes isolated from the 3- and 5-week-old groups, respectively, which confirms that F18 fimbriae are associated with diarrhoea in piglets from late stages of suckling to post-weaning, and are more related to diarrhoea in weaned than in unweaned piglets. PMID- 22079699 TI - Hyaluronic acid-based nanocarriers for intracellular targeting: interfacial interactions with proteins in cancer. AB - The therapeutic efficacy of most drugs is greatly depends on their ability to cross the cellular barrier and reach their intracellular target sites. To transport the drugs effectively through the cellular membrane and to deliver them into the intracellular environment, several interesting smart carrier systems based on both synthetic or natural polymers have been designed and developed. In recent years, hyaluronic acid (HA) has emerged as a promising candidate for intracellular delivery of various therapeutic and imaging agents because of its innate ability to recognize specific cellular receptors that overexpressed on diseased cells. The aim of this review is to highlight the significance of HA in cancer, and to explore the recent advances of HA-based drug carriers towards cancer imaging and therapeutics. PMID- 22079702 TI - The presence of methicillin-resistant Staphylococcus aureus on large pig breeding farms in Croatia. AB - Methicillin-resistant Staphylococcus aureus (MRSA) have emerged worldwide and have become resistant to a variety of antibiotics. MRSA colonisation in pigs was first reported from the Netherlands in 2005, where pigs were implicated as a source of human MRSA infections (Voss et al., 2005). This paper presents the first report on the presence of MRSA on large pig breeding farms in Croatia, together with the determination of the mecA gene, the results of spa typing and susceptibility to commonly used antimicrobials. Dust samples (7-11 per farm) were collected from eight large pig farms in Croatia. Of the total 68 swabs, the mecA gene was detected in 24 isolates growing on the MRSA agar. All isolates were resistant to oxacillin, tetracycline and streptomycin, and susceptible only to vancomycin, while 92% of the strains were susceptible to ciprofloxacin. Genotyping of the MRSA strains was performed by spa typing, and revealed t011 (n = 17), t034 (n = 5) and t1451 (n = 2). The results presented here predict that MRSA is present on a large number of pig farms in Croatia. PMID- 22079703 TI - Postmortem small babesia-like morphology of Babesia canis - short communication. AB - Here we report a case of canine babesiosis with unusual morphology of the causative agent. A male, seven-week-old Labrador retriever puppy, exhibiting severe anaemia and haemoglobinuria, was presented at the Clinic of Internal Medicine in February 2011. The puppy was euthanised. The most relevant pathological changes were icterus, severe splenomegaly, generalised lymphadenopathy and haemoglobin nephrosis. Samples were collected from various organs for histology within one hour post mortem. Impression smears were also prepared from the spleen after overnight storage at 4 degrees C. Tissue sections and smears showed the presence of multiple, coccoid intraerythrocytic bodies that measured 1-2 MUm and resembled small babesiae. No large piroplasms were seen. DNA was extracted from the spleen, and a conventional PCR was performed for the amplification of a 450-bp region of the 18S rRNA gene of piroplasms. The causative agent was identified as Babesia canis canis, with 99% sequence identity to other European isolates. Sequence identity to B. gibsoni was only 91%. This is the first account to verify that the morphology of the large canine piroplasm, B. canis, can be uniformly small babesia-like post mortem or following the storage of tissue samples. PMID- 22079704 TI - Osteoblastic osteosarcoma in a Grey Mouse Lemur (Microcebus murinus) - short communication. AB - The Grey Mouse Lemur (Microcebus murinus) is a nocturnal lemur species that lives only in Madagascar. It is one of the most abundant lemur species and its native populations are not endangered, but animals belonging to this species are rarely exhibited in zoos. While tumours are quite frequently described in other primates, there are very few publications about neoplasia in lemurs. In this case report we describe a mandibular osteoblastic osteosarcoma in a Grey Mouse Lemur (Microcebus murinus). To the best of the authors' knowledge, this is the first scientific article describing osteosarcoma in a prosimian and also reporting a tumour in the mandible in this taxon. PMID- 22079705 TI - Solitary adenoma in the proventriculus of a budgerigar (Melopsittacus undulatus) diagnosed by immunochemistry - short communication. AB - The authors describe a solitary adenoma in a 5.5-year-old female Budgerigar (Melopsittacus undulatus). The tumour was partially blocking the lumen of the proventriculus and filled it almost completely. Decreased passage of food towards the gizzard and the intestines developed in the bird as result of the obstruction, which periodically hindered the passage, leading to slow emaciation. An epithelial tumour composed of irregular glandular acini was diagnosed by histological examination. Immunohistochemical reaction with pancytokeratin showed a positive cytoplasmic reaction both in the neoplastic and the normal glandular structures. PMID- 22079706 TI - Effect of the periparturient period on serum lipid and cholesterol lipoprotein concentrations in goats (Capra hircus). AB - Blood samples were taken from 12 goats during the periparturient period (4 and 1 weeks before and 2, 10 and 30 days after delivery), and from 10 nonpregnant goats. The following variables were determined: total lipids (TL), triacylglycerol (TG), total cholesterol (TCH) and high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol fractions. One week before delivery TL (2.32 +/- 0.12 g/l, P <= 0.05), TG (0.32 +/- 0.16 mmol/l, P <= 0.001) and TCH concentrations (1.65 +/- 0.42 mmol/l, P <= 0.05) were significantly increased as compared to non-pregnant goats (2.08 +/- 0.28 g/l, 0.15 +/- 0.05 mmol/l, 1.38 +/- 0.19 mmol/l, respectively). After delivery, the concentrations of TL, TG, TCH and HDL decreased significantly. The lowest TG concentration was observed 2 days after delivery (0.18 +/- 0.02 mmol/l), while TL (1.73 +/- 0.21 g/l), TCH (0.95 +/- 0.21 mmol/l) and HDL (0.74 +/- 0.16 mmol/l) reached the lowest level 10 days after delivery. Two days after delivery a significant increase of LDL concentration was observed (0.38 +/- 0.04 mmol/l); however, ten days after delivery a threefold decrease was shown in the LDL concentration (0.12 +/- 0.04 mmol/l). A month after delivery all the variables studied reached levels similar to those measured in non-pregnant goats. PMID- 22079707 TI - Tetrodotoxin- and resiniferatoxin-induced changes in paracervical ganglion ChAT- and nNOS-IR neurons supplying the urinary bladder in female pigs. AB - The aim of the present study was to establish the effect of intravesical administration of resiniferatoxin (RTX) and tetrodotoxin (TTX) on the chemical coding of paracervical ganglion (PCG) neurons supplying the urinary bladder in the pig. In order to identify the PCG neurons innervating the bladder, retrograde tracer Fast Blue was injected into the bladder wall prior to intravesical RTX or TTX administration. Consequent application of immunocytochemical methods revealed that in the control group 76.82% of Fast Blue positive PCG neurons contain nitric oxide synthetase (nNOS), and 66.92% contain acetylcholine transferase (ChAT). Intravesical infusion of RTX resulted in a reduction of the nNOS-IR neurons to 57.74% and ChAT-IR to 57.05%. Alternative administration of TTX induced an increase of nNOS-IR neurons up to 79.29% and a reduction of the ChAT-IR population down to 3.73% of the Fast Blue positive PCG cells. Our data show that both neurotoxins affect the chemical coding of PCG cells supplying the porcine urinary bladder, but the effects of their action are different. Moreover, these results shed light on the possible involvement of NO-ergic and cholinergic neurons in the mechanisms of therapeutic action exerted by RTX and TTX in curing the overactive bladder disorder. PMID- 22079708 TI - Impact of oxidative stress on male fertility - a review. AB - Oxidative stress is a state related to increased cellular damage caused by oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS). It is a serious condition, as ROS and their metabolites attack DNA, lipids and proteins, alter enzymatic systems and cell signalling pathways, producing irreparable alterations, cell death and necrosis. While small amounts of ROS have been shown to be required for several functions of spermatozoa, their excessive levels can negatively impact the quality of spermatozoa and impair their overall fertilising capacity. These questions have recently attracted the attention of the scientific community; however, research aimed at exploring the role of oxidative stress and antioxidants associated with male fertility is still at its initial stages. This review summarises the current facts available in this field and intends to stimulate interest in basic and clinical research, especially in the development of effective methods for the diagnosis and therapy of semen damage caused by oxidative stress. PMID- 22079709 TI - Plasma progesterone, metabolic hormones and beta-hydroxybutyrate in Holstein Friesian cows after superovulation. AB - Metabolic hormones [insulin, leptin, insulin-like growth factor-I (IGF-I), thyroxine (T4) and triiodothyronine (T3)], progesterone (P4) and beta hydroxybutyrate (BHB) serum concentrations were evaluated and their effect on the superovulation results of donor cows was investigated in a semi-arid environment. Body weight, body condition score (BCS) and lactation stage were also included in the analysis. Twenty-three Holstein-Friesian cows were superovulated with 600 IU FSHp following the routine procedure and flushed on day 7 in a Multiple Ovulation and Embryo Transfer Centre in the semi-arid area of Brazil. The corpora lutea (CL) were counted and blood samples were collected for assays. All of the hormones investigated and BHB serum concentrations were within the physiological ranges. There was a positive correlation between hormones, except between BHB and all the others. The leptin level was influenced by feeding status, as indicated by the BCS. Insulin, T4, T3 and BHB levels were affected by milking status. Dry cows had higher levels of all hormones except BHB. An optimum level of leptin resulted in the highest number of CL, while the linear increase of P4, T4 and IGF significantly increased the number of CL. PMID- 22079710 TI - Effect of season and photoperiod on the time of first postpartum ovulation in Awassi ewes. AB - Seasonal differences in the resumption of postpartum ovarian activity, milk production and periparturient metabolic status were investigated in lactating non suckling dairy Awassi sheep in two consecutive experiments. In Experiment 1, autumn-lambing (AL, n = 27) and spring-lambing (SL, n = 37) ewes were investigated. Ovarian activity was monitored by means of individual progesterone (P4) profiles from day 5 to day 100 post partum. Most of the AL dams (89%) ovulated till day 35 after parturition and became cyclic thereafter. Incidence of persistent corpus luteum (CLP) and short luteal phases (sCL) was frequent (18% and 29%, respectively) among non-conceiving dams. In contrast, only 24% of the SL ewes ovulated before day 35. P4 levels during the luteal phase were lower in cyclic animals, and the cycle was longer in SL than in AL animals. No CLP or sCL was detected in the spring-lambing group, and 61% of SL ewes remained acyclic till the end of the trial. Lactation length was significantly longer in SL dams than in AL ewes (P = 0.008). According to the plasma metabolites (BHB, NEFA) and metabolic hormones (insulin, IGF-I, thyroxine) examined, negative energy balance did not appear in any of the animals. However, seasonal differences were seen in IGF-I and thyroxine levels, which were higher in the SL dams. In Experiment 2, influence of additional lighting was studied in autumn-lambing ewes. The long-day photoperiod (LD, n = 23) group was exposed to artificial light from sunset till midnight (approx. 16 h light/8 h dark) from some weeks before the expected date of delivery in mid-September until the end of December. The control group (n = 25) experienced only natural daylength. The first postpartum ovulation tended to occur later in the LD animals than in the controls (P = 0.047). The lactation of the LD group tended to be longer (P = 0.061). NEFA, BHB, insulin, IGF-I and thyroxine levels did not differ between the groups. CONCLUSIONS: (i) The ovarian function of the Awassi population is seasonal under temperate continental climate conditions. (ii) The first postpartum ovulation of non-suckling, autumn-lambing dams may occur very early, even before the completion of uterine involution. (iii) Additional artificial lighting may delay the time of first postpartum ovulation in AL ewes. (iv) Postpartum negative energy balance is unlikely to occur in dairy Awassi ewes even in high-producing intensive systems. PMID- 22079711 TI - Profiles of seroconversion to porcine circovirus type 2 in herds affected and not affected by postweaning multisystemic wasting syndrome. AB - The aim of the present study was to explore the usefulness of serological methods in the diagnosis of postweaning multisystemic wasting syndrome (PMWS). The study was carried out in 4 PMWS-affected and 6 control farms. Based on the serological profiles, infection with porcine circovirus type 2 (PCV2) was determined to take place at 3-7 weeks of age in the PMWS-affected and at 3-11 weeks of age in the control farms. To compare the dynamics of seroconversion to PCV2 among farms, cross-sectional serological profiles were normalised in relation to the inferred age of infection. The results indicated that the proportion of seropositive pigs increased significantly slower in the affected herds. The most pronounced difference was observed about 4 weeks after infection, when the proportion of seropositive pigs ranged from 0 to 53.3% and from 70 to 100% in PMWS-affected and control herds, respectively. Mean antibody titres at that age were also significantly lower in the affected farms. These observations suggest a delay in the production of PCV2-specific antibodies and indicate that serological methods may be helpful in identifying herds with a high risk of PMWS. PMID- 22079712 TI - Chitosan nanoconstructs for improved oral delivery of low molecular weight heparin: In vitro and in vivo evaluation. AB - The aim of present study was to investigate the potential of mucoadhesive polymer chitosan (CS) and N-trimethyl chitosan (TMC) based nanoparticulate systems for oral bioavailability enhancement of low molecular weight heparin (LMWH). The TMC was synthesized by methylation of chitosan followed by characterization using infrared spectroscopy and (1)H-NMR spectroscopy. The IR and NMR spectra of TMC confirmed the presence of trimethyl groups and estimated the degree of quaternization for TMC about 46%. TMC nanoparticles were then prepared by ionic gelation method. The developed CS-NPs and TMC-NPs were characterized for various parameters including morphology, particle size, zeta potential, entrapment efficiency, in vitro release behavior and storage stability at different temperature and simulated gastrointestinal tract conditions. The fluorescent microscopy study confirmed the higher particle uptake of TMC-NPs by gastrointestinal epithelium in comparison to the CS-NPs. The concentration of LMWH in the systemic circulation followed by oral administration of formulations was estimated using FXa chromogenic assay. A significant increase (p<0.05) in the oral bioavailability of LMWH was observed with TMC-NPs than both CS-NPs as well as plain LMWH solution. These findings suggested that TMC nanoparicles hold promise for oral delivery of LMWH and clinical applicability for the treatment of vascular disorders like deep vein thrombosis and pulmonary embolism, etc. PMID- 22079713 TI - Evaluation of the influence of ionization states and spacers in the thermotropic phase behaviour of amino acid-based cationic lipids and the transfection efficiency of their assemblies. AB - The influence of both the ionization states and the hydrocarbon chain spacer of a series of amino acid-based cationic lipids was evaluated in terms of gene delivery efficiency and cytotoxicity to the COS-7 cell line and compared with that of Lipofectamine 2000. We synthesized a series of amino acid-based cationic lipids with different ionization states (i.e., -NH(2), -NH(3)(+)Cl(-) or NH(3)(+)TFA(-)) in the lysine head group and different hydrocarbon chain spacers (i.e., 0, 3, 5 or 7 carbon atoms) between the hydrophilic head group and hydrophobic moieties. In the 3-carbon series, the cationic assemblies formed a micellar structure in the presence of -NH(3)(+)Cl(-) and a vesicular structure both in the presence of -NH(2) and -NH(3)(+)TFA(-). Differential scanning calorimetry (DSC) data revealed a significantly lower (8.1 degrees C) gel-to liquid crystalline phase transition temperature for cationic assemblies bearing NH(3)(+)TFA(-) when compared to their -NH(2) counterparts. Furthermore, the zeta potential of cationic assemblies having -NH(3)(+)TFA(-) in the hydrophilic head group was maximum followed by -NH(3)(+)Cl(-) and -NH(2) irrespective of their hydrocarbon chain spacer length. The gene delivery efficiency in relation to the ionization states of the hydrophilic head group was as follows: -NH(3)(+)TFA(-)> NH(3)(+)Cl(-)>-NH(2). PMID- 22079714 TI - Cocrystallization and amorphization induced by drug-excipient interaction improves the physical properties of acyclovir. AB - Although acyclovir is one of the most important antiviral drugs used today, there are several problems with its physical properties. The aim of this study is to prepare cocrystals or amorphous complex of acyclovir using drug-excipient interactions to improve the physical properties of the drug, especially its dissolution rate and transdermal absorption. Screening for formation of cocrystals and the presence of amorphous acyclovir was conducted with various pharmaceutical excipinents, with the use of the solution-crystallization method and liquid-assisted cogrinding. The potential cocrystalline phase and the amorphized complex were characterized by PXRD, TG/DTA, IR, DSC and HPLC techniques. The screening indicated that acyclovir formed novel cocrystals with tartaric acid and was amorphized with citric acid. The acyclovir-tartaric acid cocrystal (ACV-TA cocrystal) structure was determined from synchrotron X-ray powder diffraction data. T(g) of the amorphous acyclovir-citric acid compound (ACV-CA amorphous) was determined by DSC. The initial dissolution rate of the ACV TA cocrystals was considerably faster than that of anhydrous acyclovir. In vitro skin permeation of ACV-CA amorphous from polyethylene glycol (PEG) ointment was remarkably higher than that of the crystalline acyclovir. We successfully improved the physical properties of acyclovir by the cocrystallization and amorphization techniques, using pharmaceutical excipients. PMID- 22079715 TI - Investigation of preparation methods on surface/bulk structural relaxation and glass fragility of amorphous solid dispersions. AB - The objective of this study was to investigate the effect of preparation methods on the surface/bulk molecular mobility and glass fragility of solid dispersions. Solid dispersions containing indomethacin and PVP K30 were chosen as the model system. An inverse gas chromatography method was used to determine the surface structural relaxation of the solid dispersions and these data were compared to those for bulk relaxation obtained by DSC. The values of tau(beta) for the surface relaxation were 4.6, 7.1 and 1.8h for melt quenched, ball milled and spray dried solid dispersions respectively, compared to 15.6, 7.9 and 9.8h of the bulk. In all systems, the surface had higher molecular mobility than the bulk. The glass fragility of the solid dispersions was also influenced by the preparation methods with the most fragile system showing the best stability. The zero mobility temperature (T(0)) was used to correlate with the physical stability of the solid dispersions. Despite having similar T(g) (65 degrees C), the T(0) of the melt quenched, ball milled and spray dried samples were 21.6, 4.2 and 16.7 degrees C respectively which correlated well with their physical stability results. Therefore, T(0) appears to be a better indicator than T(g) for predicting stability of amorphous materials. PMID- 22079716 TI - Novel diphenyl dimethyl bicarboxylate provesicular powders with enhanced hepatocurative activity: preparation, optimization, in vitro/in vivo evaluation. AB - Diphenyl dimethyl bicarboxylate (DDB) is a hepatocurative agent used for treatment of various liver diseases. However, DDB therapeutic effectiveness is restricted by its low oral bioavailability that arises from its poor solubility and dissolution. Aiming at surmounting the aforementioned restrictions, DDB provesicular dry powders exemplified by proniosomes and proliposomes were prepared using film-deposition technique employing sorbitol as a carrier. Upon dilution with water, the provesicular powders rapidly transformed into vesicular dispersions, either liposomes or niosomes, which were characterized regarding their percent encapsulation efficiency (EE%), vesicle size and distribution, morphology and in vitro drug release. The revealed optimal provesicular powder was exposed to solid state characterization, stability testing and in vivo performance evaluation. Results showed that provesicular powders with acceptable flowability can be prepared using a weight ratio of lipids mixture to sorbitol of 1:20. Proniosomal powder composed of Tween 80:cholesterol:stearylamine in molar ratio 7:3:0.5 loaded on sorbitol was selected as the optimal formulation as it showed the highest EE% and dissolution enhancement for DDB. The elevated levels of liver enzymes in hepatically injured Albino Wister rats were significantly reduced (P<0.05) after oral administration of the optimal proniosomal powder in comparison to free DDB. This improvement was confirmed histopathologically by minimizing the associated hepatic injury. Accordingly, proniosomes can be assertively considered as a promising stable precursor for immediate preparation of niosomal carrier for DDB with enhanced dissolution and hepatocurative activity. PMID- 22079717 TI - Coated chitosan pellets containing rutin intended for the treatment of inflammatory bowel disease: in vitro characteristics and in vivo evaluation. AB - Preparation of coated pellets intended for rutin colon delivery, their evaluation in vitro and in vivo in experimental colitis in rats was the purpose of this study. Pellets were obtained using extrusion/spheronization and coated with three types of coatings (caffeic acid/hypromellose/alginic acid; sodium alginate/hypromellose/zinc acetate; sodium alginate/chitosan). Dissolution using buffers of pH values, beta-glucosidase and times corresponding to gastrointestinal tract (GIT) was provided. Pellets coated with alginate/chitosan showed low rutin dissolution (12-14%) in upper GIT conditions and fast release (87-89%) under colon conditions; that is a good presumption of intended rutin release. After colitis induction and development, the rats were treated with pellets and rutin solution administered orally, solution also rectally. Colon/body weight ratio, myeloperoxidase activity and histological evaluation were performed. Rutin was able to promote colonic healing at the dose of 10mg/kg: colon/body weight ratio decreased and myeloperoxidase activity was significantly suppressed. Pellets coated with alginate/chitosan applied orally and rutin solution administered rectally showed the best efficacy. The combination of rutin as natural product, mucoadhesive chitosan degraded in the colon and sodium alginate as the main coating substance in the form of pellets create a promising preparation for therapy of this severe illness. PMID- 22079718 TI - Stable and efficient delivery of docetaxel by micelle-encapsulation using a tripodal cyclotriphosphazene amphiphile. AB - Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu)(2)Et](3) (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD(50) value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies. PMID- 22079719 TI - Polymorphic and kinetic investigation of adefovir dipivoxil during phase transformation. AB - To search polymorphs of adefovir dipivoxil (AD), the polymorphic transformation approach in solution was developed. Also, the kinetics of polymorphic transformation was investigated to effectively control polymorphs. The AD crystals were obtained by crystallization at -10 degrees C, and then the polymorphic transformation was induced by raising temperature. The polymorphs of AD were confirmed using DSC, XRD and solubility analyses. The polymorphic fraction during transformation was monitored for kinetic investigation. Via polymorphic transformation in solution, four polymorphs of AD were found and two of them were new (NF-I, NF-II). The DSC analysis revealed that solvate form (NF I) was changed to form-V in solid state, and then re-crystallized to NF-II at 93 degrees C, and finally became form-I at 97 degrees C. This serial change of polymorphs in DSC was identical to polymorphic transformation sequence in solution. The kinetic rates of polymorphic transformation described by nucleation and mass transfer theories were well matched with experimental measurement. The polymorphic transformation approach was effective to search polymorphs of which the structure was changed to the other one in the solution. The kinetic information of polymorphic transformation predicted by Volmer's nucleation model and Stokes-Einstein diffusion equation was valuable for exact control of polymorphic purity. PMID- 22079720 TI - Aerosolized semifluorinated alkanes as excipients are suitable for inhalative drug delivery--a pilot study. AB - Semifluorinated alkanes (SFAs) have been described as potential excipients for pulmonary drug delivery, but proof of their efficacy is still lacking. We tested whether SFA formulations with the test drug ibuprofen can be nebulised and evaluated their pharmacokinetics. Physico-chemical properties of five different ibuprofen formulations were evaluated: an aqueous solution (H2O), two different SFAs (perfluorohexyloctane (F6H8), perfluorobutylpentane (F4H5)) with and without ethanol (SFA/EtOH). Nebulisation was performed with a jet catheter system. Inhalative characteristics were evaluated by laser diffraction. A confirmative animal study with an inhalative single-dose (6 mg/kg) of ibuprofen with each formulation was performed in anaesthetised healthy rabbits. Plasma samples at defined time points and lung tissue harvested after the 6-h study period were analyzed by HPLC-MS/MS. Pharmacokinetics were calculated using a non-compartment model. All formulations were nebulisable. No differences in aerodynamic diameters (MMAD) were detected between SFA and SFA/EtOH. The ibuprofen plasma concentration time curve (AUC) was highest with F4H5/EtOH. In contrast, F6H8/EtOH had the highest deposition of ibuprofen into lung tissue but the lowest AUC. All tested SFA and SFA/EtOH formulations are suitable for inhalation. F4H5/EtOH formulations might be used for rapid systemic availability of drugs. F6H8/EtOH showed intrapulmonary deposition of the test drug. PMID- 22079721 TI - Variation in use of androgen suppression with external-beam radiotherapy for nonmetastatic prostate cancer. AB - PURPOSE: To describe practice patterns associated with androgen suppression (AS) stratified by disease risk group in patients undergoing external-beam radiotherapy (EBRT) for localized prostate cancer. METHODS AND MATERIALS: We identified 2,184 low-risk, 2,339 intermediate-risk, and 2,897 high-risk patients undergoing EBRT for nonmetastatic prostate cancer diagnosed between January 1, 2004, and December 31, 2005, in the linked Surveillance, Epidemiology, and End Results-Medicare database. We examined the association of patient, clinical, and demographic characteristics with AS use by multivariate logistic regression. RESULTS: The proportions of patients receiving AS for low-risk, intermediate risk, and high-risk prostate cancer were 32.2%, 56.3%, and 81.5%, respectively. AS use among men in the low-risk disease category varied widely, ranging from 13.6% in Detroit to 47.8% in Kentucky. We observed a significant decline in AS use between 2004 and 2005 within all three disease risk categories. Men aged >=75 years or with elevated comorbidity levels were more likely to receive AS. CONCLUSION: Our results identified apparent overuse and underuse of AS among men within the low-risk and high-risk disease categories, respectively. These results highlight the need for clinician and patient education regarding the appropriate use of AS. Practice patterns among intermediate-risk patients reflect the clinical heterogeneity of this population and underscore the need for better evidence to guide the treatment of these patients. PMID- 22079722 TI - Risk factors of developing long-lasting breast pain after breast cancer radiotherapy. AB - PURPOSE: Postoperative radiotherapy decreases breast cancer mortality. However, studies have revealed a long-lasting breast pain among some women after radiotherapy. The purpose of this study was to identify risk factors that contribute to breast pain after breast cancer radiotherapy. METHODS AND MATERIALS: We identified 1,027 recurrence-free women in two cohorts of Swedish women treated for breast cancer. The women had breast-conserving surgery and postoperative radiotherapy, the breast was treated to 48 Gy in 2.4-Gy fractions or to 50 Gy in 2.0-Gy fractions. Young women received a boost of up to 16 Gy. Women with more than three lymph node metastases had locoregional radiotherapy. Systemic treatments were given according to health-care guidelines. Three to 17 years after radiotherapy, we collected data using a study-specific questionnaire. We investigated the relation between breast pain and potential risk modifiers: age at treatment, time since treatment, chemotherapy, photon energy, fractionation size, boost, loco-regional radiotherapy, axillary surgery, overweight, and smoking. RESULTS: Eight hundred seventy-seven women (85%) returned the questionnaires. Among women up to 39 years of age at treatment, 23.1% had breast pain, compared with 8.7% among women older than 60 years (RR 2.66; 95% CI 1.33-5.36). Higher age at treatment (RR 0.96; 95% CI 0.94-0.98, annual decrease) and longer time since treatment (RR 0.93; 95% CI 0.88-0.98, annual decrease) were related to a lower occurrence of breast pain. Chemotherapy increased the occurrence of breast pain (RR 1.72; 95% CI 1.19-2.47). In the multivariable model only age and time since treatment were statistically significantly related to the occurrence of breast pain. We found no statistically significant relation between breast pain and the other potential risk modifiers. CONCLUSIONS: Younger women having undergone breast-conserving surgery with postoperative radiotherapy report a higher occurrence of long-lasting breast pain compared to older women. Time since treatment may decrease the occurrence of pain. PMID- 22079723 TI - Prognostic factors for survival in patients treated with stereotactic radiosurgery for recurrent brain metastases after prior whole brain radiotherapy. AB - PURPOSE: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). METHODS AND MATERIALS: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. RESULTS: A total of 310 patients were analyzed, including 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. CONCLUSIONS: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS. PMID- 22079724 TI - Biochemical control with radiotherapy improves overall survival in intermediate and high-risk prostate cancer patients who have an estimated 10-year overall survival of >90%. AB - PURPOSE: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. METHODS AND MATERIALS: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10 year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. RESULTS: Median follow-up was 125 months (range, 51-176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%-94.1%) and 62.1% (95% CI 52.9%-71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%-100%) and 79.8% (95% CI 68.0%-91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p < 0.001) were statistically significant. CONCLUSION: Biochemical control translates into improved overall survival in patients with high or intermediate risk disease and an estimated 10-year overall survival of >90%. PMID- 22079725 TI - Phase II study of short-course radiotherapy plus concomitant and adjuvant temozolomide in elderly patients with glioblastoma. AB - PURPOSE: Radiotherapy (RT) and chemotherapy may prolong survival in older patients (age >=70 years) with glioblastoma multiforme (GBM), although the survival benefits remain poor. This Phase II multicenter study was designed to evaluate the efficacy and safety of an abbreviated course of RT plus concomitant and adjuvant temozolomide (TMZ) in older patients with GBM. PATIENTS AND METHODS: Seventy-one eligible patients 70 years of age or older with newly diagnosed GBM and a Karnofsky performance status >=60 were treated with a short course of RT (40 Gy in 15 fractions over 3 weeks) plus TMZ at the dosage of 75 mg/m(2) per day followed by 12 cycles of adjuvant TMZ (150-200 mg/m(2) for 5 days during each 28 day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival and toxicity. RESULTS: The Median OS was 12.4 months, and the 1-year and 2-year OS rates were 58% and 20%, respectively. The median and 1-year rates of progression-free survival were 6 months and 20%, respectively. All patients completed the planned programme of RT. Grade 3 or 4 adverse events occurred in 16 patients (22%). Grade 3 and 4 neutropenia and/or thrombocytopenia occurred in 10 patients (15%), leading to the interruption of treatment in 6 patients (8%). Nonhematologic Grade 3 toxicity was rare, and included fatigue in 4 patients and cognitive disability in 1 patient. CONCLUSIONS: A combination of an abbreviated course of RT plus concomitant and adjuvant TMZ is well tolerated and may prolong survival in elderly patients with GBM. Future randomized studies need to evaluate the efficacy and toxicity of different schedules of RT in association with chemotherapy. PMID- 22079726 TI - A Phase I study of chemoradiotherapy with use of involved-field conformal radiotherapy and accelerated hyperfractionation for Stage III non-small cell lung cancer: WJTOG 3305. AB - PURPOSE: A Phase I study to determine a recommended dose of thoracic radiotherapy using accelerated hyperfractionation for unresectable non-small-cell lung cancer was conducted. METHODS AND MATERIALS: Patients with unresectable Stage III non small-cell lung cancer were treated intravenously with carboplatin (area under the concentration curve 2) and paclitaxel (40 mg/m(2)) on Days 1, 8, 15, and 22 with concurrent twice-daily thoracic radiotherapy (1.5 Gy per fraction) beginning on Day 1 followed by two cycles of consolidation chemotherapy using carboplatin (area under the concentration curve 5) and paclitaxel (200 mg/m(2)). Total doses were 54 Gy in 36 fractions, 60 Gy in 40 fractions, 66 Gy in 44 fractions, and 72 Gy in 48 fractions at Levels 1 to 4. The dose-limiting toxicity, defined as Grade >=4 esophagitis and neutropenic fever and Grade >=3 other nonhematologic toxicities, was monitored for 90 days. RESULTS: Of 26 patients enrolled, 22 patients were assessable for response and toxicity. When 4 patients entered Level 4, enrollment was closed to avoid severe late toxicities. Dose-limiting toxicities occurred in 3 patients. They were Grade 3 neuropathy at Level 1 and Level 3 and Grade 3 infection at Level 1. However, the maximum tolerated dose was not reached. The median survival time was 28.6 months for all patients. CONCLUSIONS: The maximum tolerated dose was not reached, although the dose of radiation was escalated to 72 Gy in 48 fractions. However, a dose of 66 Gy in 44 fractions was adopted for this study because late toxicity data were insufficient. PMID- 22079727 TI - Long-term results of radiochemotherapy for solitary lymph node metastasis after curative resection of esophageal cancer. AB - PURPOSE: To evaluate the long-term efficacy and toxicity of definitive radiochemotherapy for solitary lymph node metastasis after curative surgery of esophageal cancer. METHODS AND MATERIALS: We performed a retrospective review of 35 patients who underwent definitive radiochemotherapy at Tohoku University Hospital between 2000 and 2009 for solitary lymph node metastasis after curative esophagectomy with lymph node dissection for esophageal cancer. Radiotherapy doses ranged from 60 to 66 Gy (median, 60 Gy). Concurrent chemotherapy was platinum based in all patients. The endpoints of the present study were overall survival, cause-specific survival, progression-free survival, irradiated-field control, overall tumor response, and prognostic factors. RESULTS: The median observation period for survivors was 70.0 months. The 5-year overall survival was 39.2% (median survival, 39.0 months). The 5-year cause-specific survival, progression-free survival, and irradiated-field control were 43.3%, 31.0% and 59.9%, respectively. Metastatic lesion, size of the metastatic lymph node, and performance status before radiochemotherapy were significantly correlated with prognosis. Complete response and partial response were observed in 22.9% and 57.1% of the patients, respectively. There was no Grade 3 or higher adverse effect based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0) in the late phase. CONCLUSIONS: Based on our study findings, approximately 40% of patients with solitary lymph node metastasis after curative resection for esophageal cancer have a chance of long-term survival with definitive radiochemotherapy. PMID- 22079728 TI - Early-stage primary bone lymphoma: a retrospective, multicenter Rare Cancer Network (RCN) Study. AB - PURPOSE: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. PATIENTS AND METHODS: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242). RESULTS: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score <=1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. CONCLUSION: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome. PMID- 22079729 TI - Expansion/de-expansion tool to quantify the accuracy of prostate contours. AB - PURPOSE: Accurate delineation of the prostate gland on computed tomography (CT) remains a persistent challenge and continues to introduce geometric uncertainty into the planning and delivery of external beam radiotherapy. We, therefore, developed an expansion/de-expansion tool to quantify the contour errors and determine the location of the deviations. METHODS AND MATERIALS: A planning CT scan and magnetic resonance imaging scan were prospectively acquired for 10 patients with prostate cancer. The prostate glands were contoured by 3 independent observers using the CT data sets with instructions to contour the prostate without underestimation but to minimize overestimation. The standard prostate for each patient was defined using magnetic resonance imaging and CT on multiple planes. After registration of the CT and magnetic resonance imaging data sets, the CT-defined prostates were scored for accuracy. The contours were defined as ideal if they were within a 2.5-mm expansion of the standard without underestimation, acceptable if they were within a 5.0-mm expansion and a 2.5-mm de-expansion, and unacceptable if they extended >5.0 mm or underestimated the prostate by >2.5 mm. RESULTS: A total of 636 CT slices were individually analyzed, with the vast majority scored as ideal or acceptable. However, none of the 30 prostate contour sets had all the contours scored as ideal or acceptable. For all 3 observers, the unacceptable contours were more likely from underestimation than overestimation of the prostate. The errors were more common at the base and apex than the mid-gland. CONCLUSIONS: The expansion/de-expansion tool allows for directed feedback on the location of contour deviations, as well as the determination of over- or underestimation of the prostate. This metric might help improve the accuracy of prostate contours. PMID- 22079730 TI - Factors associated with optimal long-term cosmetic results in patients treated with accelerated partial breast irradiation using balloon-based brachytherapy. AB - PURPOSE: To evaluate factors associated with optimal cosmetic results at 72 months for early-stage breast cancer patients treated with Mammosite balloon based accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 1,440 patients (1,449 cases) with early-stage breast cancer undergoing breast-conserving therapy were treated with balloon-based brachytherapy to deliver APBI (34 Gy in 3.4-Gy fractions). Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good (E/G) or fair/poor (F/P). Follow-up was evaluated at 36 and 72 months to establish long-term cosmesis, stability of cosmesis, and factors associated with optimal results. RESULTS: The percentage of evaluable patients with excellent/good (E/G) cosmetic results at 36 months and more than 72 months were 93.3% (n = 708/759) and 90.4% (n = 235/260). Factors associated with optimal cosmetic results at 72 months included: larger skin spacing (p = 0.04) and T1 tumors (p = 0.02). Using multiple regression analysis, the only factors predictive of worse cosmetic outcome at 72 months were smaller skin spacing (odds ratio [OR], 0.89; confidence interval [CI], 0.80-0.99) and tumors greater than 2 cm (OR, 4.96, CI, 1.53-16.07). In all, 227 patients had both a 36-month and a 72-month cosmetic evaluation. The number of patients with E/G cosmetic results decreased only slightly from 93.4% at 3 years to 90.8% (p = 0.13) at 6 years, respectively. CONCLUSIONS: APBI delivered with balloon-based brachytherapy produced E/G cosmetic results in 90.4% of cases at 6 years. Larger tumors (T2) and smaller skin spacing were found to be the two most important independent predictors of cosmesis. PMID- 22079731 TI - Four-week neoadjuvant intensity-modulated radiation therapy with concurrent capecitabine and oxaliplatin in locally advanced rectal cancer patients: a validation phase II trial. AB - PURPOSE: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. RESULTS: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96 100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. CONCLUSIONS: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients. PMID- 22079732 TI - Beta-carotene antioxidant use during radiation therapy and prostate cancer outcome in the Physicians' Health Study. AB - PURPOSE: The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians' Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases. METHODS AND MATERIALS: PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined as prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT. RESULTS: With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42-1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87-95%) in the beta-carotene group and 89% (95% CI, 84-93%) in the placebo group. CONCLUSION: The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer. PMID- 22079733 TI - Radiotherapy for early mediastinal Hodgkin lymphoma according to the German Hodgkin Study Group (GHSG): the roles of intensity-modulated radiotherapy and involved-node radiotherapy. AB - PURPOSE: Cure rates of early Hodgkin lymphoma (HL) are high, and avoidance of late complications and second malignancies have become increasingly important. This comparative treatment planning study analyzes to what extent target volume reduction to involved-node (IN) and intensity-modulated (IM) radiotherapy (RT), compared with involved-field (IF) and three-dimensional (3D) RT, can reduce doses to organs at risk (OAR). METHODS AND MATERIALS: Based on 20 computed tomography (CT) datasets of patients with early unfavorable mediastinal HL, we created treatment plans for 3D-RT and IMRT for both the IF and IN according to the guidelines of the German Hodgkin Study Group (GHSG). As OAR, we defined heart, lung, breasts, and spinal cord. Dose-volume histograms (DVHs) were evaluated for planning target volumes (PTVs) and OAR. RESULTS: Average IF-PTV and IN-PTV were 1705 cm(3) and 1015 cm(3), respectively. Mean doses to the PTVs were almost identical for all plans. For IF-PTV/IN-PTV, conformity was better with IMRT and homogeneity was better with 3D-RT. Mean doses to the heart (17.94/9.19 Gy for 3D RT and 13.76/7.42 Gy for IMRT) and spinal cord (23.93/13.78 Gy for 3D-RT and 19.16/11.55 Gy for IMRT) were reduced by IMRT, whereas mean doses to lung (10.62/8.57 Gy for 3D-RT and 12.77/9.64 Gy for IMRT) and breasts (left 4.37/3.42 Gy for 3D-RT and 6.04/4.59 Gy for IMRT, and right 2.30/1.63 Gy for 3D-RT and 5.37/3.53 Gy for IMRT) were increased. Volume exposed to high doses was smaller for IMRT, whereas volume exposed to low doses was smaller for 3D-RT. Pronounced benefits of IMRT were observed for patients with lymph nodes anterior to the heart. IN-RT achieved substantially better values than IF-RT for almost all OAR parameters, i.e., dose reduction of 20% to 50%, regardless of radiation technique. CONCLUSIONS: Reduction of target volume to IN most effectively improves OAR sparing, but is still considered investigational. For the time being, IMRT should be considered for large PTVs especially when the anterior mediastinum is involved. PMID- 22079734 TI - Common variants of GSTP1, GSTA1, and TGFbeta1 are associated with the risk of radiation-induced fibrosis in breast cancer patients. AB - PURPOSE: To provide new insights into the genetic basis of normal tissue radiosensitivity, we evaluated the association between eight polymorphic variants located in six genes related to DNA repair mechanisms, oxidative stress, and fibroblast proliferation (XRCC1 Arg399Gln, XRCC1 Arg194Trp, TP53 Arg72Pro, GSTP1 Ile105Val, GSTA1 C-69T, eNOS G894T, TGFbeta1 C-509T, and TGFbeta1 T869C) and the risk of subcutaneous fibrosis in a retrospective series of patients who received radiotherapy after breast-conserving surgery. METHODS AND MATERIALS: Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue--Subjective Objective Management Analytical scale in 257 breast cancer patients who underwent surgery plus adjuvant radiotherapy. Genotyping was conducted by polymerase chain reaction--restriction fragment length polymorphism analysis on genomic DNA extracted from peripheral blood. The association between genetic variants and the risk of moderate to severe fibrosis was evaluated by binary logistic regression analysis. RESULTS: Two hundred thirty-seven patients were available for the analysis. Among them, 41 patients (17.3%) developed moderate to severe fibrosis (Grade 2-3), and 196 (82.7%) patients displayed no or minimal fibrotic reactions (Grade 0-1). After adjustment of confounding factors, GSTP1 Ile105Val (odds ratio [OR] 2.756; 95% CI, 1.188-6.393; p = 0.018), GSTA1 C-69T (OR 3.223; 95% CI, 1.176 8.826; p = 0.022), and TGFbeta1 T869C (OR 0.295; 95% CI, 0.090-0.964; p = 0.043) polymorphisms were found to be significantly associated with the risk of Grade 2 3 radiation-induced fibrosis. In the combined analysis, carriers of three risk genotypes were found to be at higher odds for the development of Grade 2-3 fibrosis than were patients with two risk genotypes (OR 4.415; 95% CI, 1.553 12.551, p = 0.005) or with no or one risk genotype (OR 8.563; 95% CI, 2.671 27.447; p = 0.0003). CONCLUSIONS: These results suggest that functional variations in genes involved in oxidative stress response and fibroblast proliferation may modulate the development of radiation-induced fibrosis in breast cancer patients. The results of the combined analysis support the notion that approaches based on the combination of different genetic markers have the potential to predict normal tissue responses. PMID- 22079735 TI - Long-term clinical outcome of intensity-modulated radiotherapy for inoperable non small cell lung cancer: the MD Anderson experience. AB - PURPOSE: In 2007, we published our initial experience in treating inoperable non small-cell lung cancer (NSCLC) with intensity-modulated radiation therapy (IMRT). The current report is an update of that experience with long-term follow-up. METHODS AND MATERIALS: Patients in this retrospective review were 165 patients who began definitive radiotherapy, with or without chemotherapy, for newly diagnosed, pathologically confirmed NSCLC to a dose of >=60 Gy from 2005 to 2006. Early and late toxicities assessed included treatment-related pneumonitis (TRP), pulmonary fibrosis, esophagitis, and esophageal stricture, scored mainly according to the Common Terminology Criteria for Adverse Events 3.0. Other variables monitored were radiation-associated dermatitis and changes in body weight and Karnofsky performance status. The Kaplan-Meier method was used to compute survival and freedom from radiation-related acute and late toxicities as a function of time. RESULTS: Most patients (89%) had Stage III to IV disease. The median radiation dose was 66 Gy given in 33 fractions (range, 60-76 Gy, 1.8-2.3 Gy per fraction). Median overall survival time was 1.8 years; the 2-year and 3 year overall survival rates were 46% and 30%. Rates of Grade >=3 maximum TRP (TRP(max)) were 11% at 6 months and 14% at 12 months. At 18 months, 86% of patients had developed Grade >=1 maximum pulmonary fibrosis (pulmonary fibrosis(max)) and 7% Grade >=2 pulmonary fibrosis(max). The median times to maximum esophagitis (esophagitis(max)) were 3 weeks (range, 1-13 weeks) for Grade 2 and 6 weeks (range, 3-13 weeks) for Grade 3. A higher percentage of patients who experienced Grade 3 esophagitis(max) later developed Grade 2 to 3 esophageal stricture. CONCLUSIONS: In our experience, using IMRT to treat NSCLC leads to low rates of pulmonary and esophageal toxicity, and favorable clinical outcomes in terms of survival. PMID- 22079736 TI - Quality of life after hypofractionated concomitant intensity-modulated radiotherapy boost for high-risk prostate cancer. AB - PURPOSE: To evaluate the change in health-related quality of life (QOL) of patients with high-risk prostate cancer treated using hypofractionated radiotherapy combined with long-term androgen deprivation therapy. METHODS AND MATERIALS: A prospective Phase I-II study enrolled patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level >=20 ng/mL, or Gleason score 8-10. Radiotherapy consisted of 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes with a concomitant 22.5 Gy intensity-modulated radiotherapy boost to the prostate, for a total of 67.5 Gy (2.7 Gy per fraction) in 25 fractions over 5 weeks. Daily image guidance was performed using three gold seed fiducials. Quality of life was measured using the Expanded Prostate Cancer Index Composite (EPIC), a validated tool that assesses four primary domains (urinary, bowel, sexual, and hormonal). RESULTS: From 2004 to 2007, 97 patients were treated. Median follow-up was 39 months. Compared with baseline, at 24 months there was no statistically significant change in the mean urinary domain score (p = 0.99), whereas there were decreases in the bowel (p < 0.01), sexual (p < 0.01), and hormonal (p < 0.01) domains. The proportion of patients reporting a clinically significant difference in EPIC urinary, bowel, sexual, and hormonal scores at 24 months was 27%, 31%, 55%, and 60%, respectively. However, moderate and severe distress related to these symptoms was minimal, with increases of only 3% and 5% in the urinary and bowel domains, respectively. CONCLUSIONS: Hypofractionated radiotherapy combined with long-term androgen deprivation therapy was well tolerated. Although there were modest rates of clinically significant patient-reported urinary and bowel toxicity, most of this caused only mild distress, and moderate and severe effects on QOL were limited. Additional follow-up is ongoing to characterize long-term QOL. PMID- 22079737 TI - NMR for direct determination of K(m) and V(max) of enzyme reactions based on the Lambert W function-analysis of progress curves. AB - (1)H NMR spectroscopy was used to follow the cleavage of sucrose by invertase. The parameters of the enzyme's kinetics, K(m) and V(max), were directly determined from progress curves at only one concentration of the substrate. For comparison with the classical Michaelis-Menten analysis, the reaction progress was also monitored at various initial concentrations of 3.5 to 41.8mM. Using the Lambert W function the parameters K(m) and V(max) were fitted to obtain the experimental progress curve and resulted in K(m)=28mM and V(max)=13MUM/s. The result is almost identical to an initial rate analysis that, however, costs much more time and experimental effort. The effect of product inhibition was also investigated. Furthermore, we analyzed a much more complex reaction, the conversion of farnesyl diphosphate into (+)-germacrene D by the enzyme germacrene D synthase, yielding K(m)=379MUM and k(cat)=0.04s(-1). The reaction involves an amphiphilic substrate forming micelles and a water insoluble product; using proper controls, the conversion can well be analyzed by the progress curve approach using the Lambert W function. PMID- 22079738 TI - Optimization by factorial analysis of caprylic acid precipitation of non immunoglobulins from hyperimmune equine plasma for antivenom preparation. AB - Optimization of caprylic acid precipitation of equine plasma non-immunoglobulin proteins for antivenom preparation was achieved by regression analysis of the responses of three highly significant factors assayed by factorial design. The factors studied were caprylic acid concentration, plasma pH and temperature, and their response was assessed in terms of filtration speed, residual albumin, total protein content and turbidity. The results evidenced that the three variables are involved in the precipitation process. Moreover, the factors displayed significant interactions, indicating that their levels distinctly affect the optimization procedure. The best combination was 3% caprylic acid, 37 degrees C and plasma pH 4.9; under these conditions, all immunoglobulins and only 0.1% albumin remained in the supernatant, in a very fast and simple procedure. After formulation, the antivenom obtained by this procedure presented full lethality neutralizing activity and absence of protein aggregates. PMID- 22079739 TI - Arginase depletes plasma l-arginine and decreases pulmonary vascular reserve during experimental pulmonary embolism. AB - The experiments test if experimental PE causes red blood cell hemolysis, arginase release and depletion of l-arginine and determine if arginase inhibition preserves l-arginine and improves pulmonary hemodynamics during PE. Experimental PE was induced in male Sprague-Dawley rats by infusing 25 MUm microspheres (1.8 million/100 g body wt) in the jugular vein, producing moderate pulmonary hypertension. Pulmonary vascular resistance was estimated from the quotient of the right ventricular peak systolic pressure/cardiac output. Arterial plasma hemoglobin (ELISA), arginase activity (colorimetric assay) and l-arginine (high performance liquid chromatography) were determined. Arginase activity was inhibited by infusion of N-omega-hydroxy-nor-l-arginine (nor-NOHA, 400 mg/kg body wt, i.v.). Values are means +/- s.e. Five hours of PE caused red blood cell hemolysis (15-fold increase in plasma hemoglobin) and release of arginase activity (2.7-fold increase). Plasma l-arginine concentration decreased significantly from 250 +/- 20.6 to 118 +/- 6.0 MUmol/L (Control vs. PE) and estimated pulmonary vascular resistance increased 3-fold. Treatment with nor-NOHA prevented the depletion of plasma l-arginine (229 +/- 15 MUmol/L) and reduced the rise in pulmonary vascular resistance by 40%. In conclusion, experimental PE causes hemolysis, release of arginase activity, depletion of plasma l-arginine and increased estimated pulmonary vascular resistance. Inhibition of arginase activity preserves plasma l-arginine levels and improves estimated resistance, suggesting that the release of arginase during hemolysis contributes to the rise in estimated pulmonary resistance during experimental PE. PMID- 22079740 TI - Sleeping beauty--a mouse model for all cancers? AB - Sleeping Beauty (SB) is a genetically engineered insertional mutagenesis system. Its ability to rapidly induce cancer in SB-transgenic mice as well as the ease of identification of the mutated genes suggest important roles for SB in the discovery of novel cancer genes as well as the generation of models of human cancers where none currently exist. The range of SB-related tumors extends from haematopoietic to solid cancers such as hepatocellular carcinoma. This review follows the refinement of SB for different cancers and assesses its potential as a model for all cancers and a tool for cancer gene discovery. PMID- 22079741 TI - Irreversible electroporation shows efficacy against pancreatic carcinoma without systemic toxicity in mouse models. AB - Pancreatic ductal adenocarcinoma (PDAC) therapies show limited success. Irreversible electroporation (IRE) is an innovative loco-regional therapy in which high-voltage pulses are applied to induce plasma membrane defects leading to cellular death. In the present study we evaluated the feasibility of IRE against PDAC. IRE treatment exhibited significant antitumor effects and prolonged survival in mice with orthotopic xenografts. Extensive tumor necrosis, reduced tumor cell proliferation and disruption of microvessels were observed at different days post-IRE. Animals had transient increases in transaminases, amylase and lipase enzymes that normalized at 24h post-IRE. These results suggest that IRE could be an effective treatment for locally advanced pancreatic tumors. PMID- 22079742 TI - [Standardization of the gynecological emergency ultrasound examination]. AB - Standardization of the gynecological emergency ultrasound examination could allow more accurate evaluation in gynecologic or general emergency unit. A systematic set of images, "Standardized Acute Female Echography" (SAFE), was defined. In practice, four pictures are realized whatever presenting complaint (set "A"). These pictures describe the normal anatomy and allow verifying the quality of ultrasonography realization. The picture A1 is obtained by abdominal probe and investigates the Morison's pouch. The pictures A2, A3 and A4 are obtained by transvaginal probe and correspond respectively to the mid-sagittal uterus view, the right ovary and the left ovary. For each of these pictures, some quality criteria were defined allowing a control of ultrasound examination. When abnormality is detected, others pictures (set "B)" are required to describe it. These pictures are called B1 in case of intra-uterine abnormality and B2 in case of adnexal abnormality. This standardization of pelvic ultrasonography could allow a quality control and a delegation of the ultrasound examination by training physicians or diagnostic medical sonographers without repetition of the examination. SAFE could be a reference in the field of gynecological emergencies imaging picture by improving diagnostic and therapeutic management. PMID- 22079743 TI - [Surgery for the management of ovarian endometriomas: from the physiopathology to the pre-, peri- and postoperative treatment]. AB - Good knowledge of physiopathology, surgical techniques and of the literature allows for an adequate treatment of ovarian endometrioma. Preoperative medical treatment has not shown to be efficient and might be adapted to each patient (continuation or initiation of hormonal treatment in case of symptomatology, will for contraception, association with functional cyst). Laparoscopy is the mandatory surgical approach. Cystectomy is the surgical technique of choice but may affect normal ovarian tissu. Surgical technique should be meticulous in particular with respect to the hilum of the ovary. Exclusive coagulation using bipolar is not recommended. A hybrid technique associating both cystectomy and vaporization (laser or Plasmajet((c))) at the level of the hilum of the ovary could be interesting. Hemostasis should be spontaneous or obtained with bipolar coagulation with parcimony. Ovarian suture is a solution. Extra-ovarian lesions should be carefully searched for and treated. Anti-adhesion products should be applied. Postoperative medical treatment decreases recurrence and should be systematic for patients who do not want to conceive. Multidisciplinary approach is essential. PMID- 22079744 TI - [Trisomy 21 by isochromosome: a case report of true false negative of chorionic villi sampling]. AB - We report a rare case of true false negative of chorionic villi sampling for a child with Down syndrome. A chorionic villi sampling was performed for a nuchal translucency at the first trimester. The karyotype was 46,XX for the short and the long-term culture. Because of facial dysmorphy and cardiopathy to the child, a karytoype was proposed. This postnatal karyotype showed a trisomy 21, by isochromosome 46,XX,i(21)(q10). We expose the mechanism of true false negative of chorionic villi sampling, and particularly the role of isochromosome in this case. PMID- 22079745 TI - Health-related quality of life among participants in the SMART weight loss trial. AB - Obesity has been associated with a decreased health-related quality of life (HRQoL); however, the association between weight change and HRQoL is unclear. This secondary analysis of the SMART (Self Monitoring And Recording using Technology) trial, a clinical trial of behavioral weight loss treatment, provides evidence that quality of life improves with weight loss. PMID- 22079746 TI - "Reading between the lines" of flow sheet data: nurses' optional documentation associated with cardiac arrest outcomes. PMID- 22079747 TI - Part 2: enhancing heart failure home management: integrated evidence for a new family caregiver educational plan. AB - This article describes how the qualitative data integrated from patients, health care professionals, and family caregivers have been developed into a new heart failure (HF) educational plan for family caregivers to manage the complexities of HF self-management at home. In addition, the educational plan describes potential strategies and teaching materials based on these integrated data. PMID- 22079748 TI - Cardiac and pulmonary arterial remodeling after sinoaortic denervation in normotensive rats. AB - Blood pressure variability (BPV) and baroreflex dysfunction may contribute to end organ damage process. We investigated the effects of baroreceptor deficit (10 weeks after sinoaortic denervation - SAD) on hemodynamic alterations, cardiac and pulmonary remodeling. Cardiac function and morphology of male Wistar intact rats (C) and SAD rats (SAD) (n=8/group) were assessed by echocardiography and collagen quantification. BP was directly recorded. Ventricular hypertrophy was quantified by the ratio of left ventricular weight (LVW) and right ventricular weight (RVW) to body weight (BW). BPV was quantified in the time and frequency domains. The atrial natriuretic peptide (ANP), alpha-skeletal actin (alpha-skelectal), collagen type I and type III genes mRNA expression were evaluated by RT-PCR. SAD did not change BP, but increased BPV (11+/-0.49 vs. 5+/-0.3 mmHg). As expected, baroreflex was reduced in SAD. Pulmonary artery acceleration time was reduced in SAD. In addition, SAD impaired diastolic function in both LV (6.8+/-0.26 vs. 5.02+/-0.21 mmHg) and RV (5.1+/-0.21 vs. 4.2+/-0.12 mmHg). SAD increased LVW/BW in 9% and RVW/BW in 20%, and augmented total collagen (3.8-fold in LV, 2.7-fold in RV, and 3.35-fold in pulmonary artery). Also, SAD increased type I (~6-fold) and III (~5-fold) collagen gene expression. Denervation increased ANP expression in LV (75%), in RV (74%) and increased alpha-skelectal expression in LV (300%) and in RV (546%). Baroreflex function impairment by SAD, despite not changing BP, induced important adjustments in cardiac structure and pulmonary hypertension. These changes may indicate that isolated baroreflex dysfunction can modulate target tissue damage. PMID- 22079749 TI - Analytical comparison of the cobas HPV Test with Hybrid Capture 2 for the detection of high-risk HPV genotypes. AB - Human papillomavirus (HPV) is a causal agent of cervical cancer, and persistent HPV16 or HPV18 infection carries a particularly high risk. The cobas HPV Test (cobas) provides individual HPV16/HPV18 genotyping with a simultaneous result for 12 other high-risk HPV (hrHPV) genotypes. Its analytical performance for hrHPV genotype detection was retrospectively evaluated against the digene Hybrid Capture 2 HPV DNA test (HC2), in three European centers, in 1360 cervical samples. Both HPV tests performed similarly, with no significant difference in the number of positive and negative samples identified by each test and good agreement between the tests was observed. Discordant samples were analyzed with the Linear Array HPV genotyping test. More low-risk HPV (lrHPV) genotypes were detected in HC2-positive/cobas-negative samples compared with HC2-negative/cobas positive samples. Conversely, more hrHPV genotypes were detected in HC2 negative/cobas-positive samples compared with HC2-positive/cobas-negative samples. Eight HC2-negative/cobas-positive samples were positive for HPV16 compared with five HC2-positive/cobas-negative samples; HPV18 was detected in one HC2-negative/cobas-positive sample and one HC2-positive/cobas-negative sample. The cobas HPV Test demonstrates comparable analytical performance to the HC2 test, but with a lower rate of cross-reactivity with lrHPV genotypes, and has the advantage of simultaneously providing HPV16/HPV18 identification. PMID- 22079750 TI - Maximizing microbial degradation of perchlorate using a genetic algorithm: Media optimization. AB - Microbial communities are under constant influence of physical and chemical components in ecosystems. Shifts in conditions such as pH, temperature or carbon source concentration can translate into shifts in overall ecosystem functioning. These conditions can be manipulated in a laboratory setup using evolutionary computation methods such as genetic algorithms (GAs). In work described here, a GA methodology was successfully applied to define sets of environmental conditions for microbial enrichments and pure cultures to achieve maximum rates of perchlorate degradation. Over the course of 11 generations of optimization using a GA, we saw a statistically significant 16.45 and 16.76-fold increases in average perchlorate degradation rates by Dechlorosoma sp. strain KJ and Dechloromonas sp. strain Miss R, respectively. For two bacterial consortia, Pl6 and Cw3, 5.79 and 5.75-fold increases in average perchlorate degradation were noted. Comparison of zero-order kinetic rate constants for environmental conditions in GA-determined first and last generations of all bacterial cultures additionally showed marked increases. PMID- 22079751 TI - Evaluation of parallel milliliter-scale stirred-tank bioreactors for the study of biphasic whole-cell biocatalysis with ionic liquids. AB - As clear structure-activity relationships are still rare for ionic liquids, preliminary experiments are necessary for the process development of biphasic whole-cell processes involving these solvents. To reduce the time investment and the material costs, the process development of such biphasic reaction systems would profit from a small-scale high-throughput platform. Exemplarily, the reduction of 2-octanone to (R)-2-octanol by a recombinant Escherichia coli in a biphasic ionic liquid/water system was studied in a miniaturized stirred-tank bioreactor system allowing the parallel operation of up to 48 reactors at the mL scale. The results were compared to those obtained in a 20-fold larger stirred tank reactor. The maximum local energy dissipation was evaluated at the larger scale and compared to the data available for the small-scale reactors, to verify if similar mass transfer could be obtained at both scales. Thereafter, the reaction kinetics and final conversions reached in different reactions setups were analysed. The results were in good agreement between both scales for varying ionic liquids and for ionic liquid volume fractions up to 40%. The parallel bioreactor system can thus be used for the process development of the majority of biphasic reaction systems involving ionic liquids, reducing the time and resource investment during the process development of this type of applications. PMID- 22079752 TI - lac operon induction in Escherichia coli: Systematic comparison of IPTG and TMG induction and influence of the transacetylase LacA. AB - Most commonly used expression systems in bacteria are based on the Escherichia coli lac promoter. Furthermore, lac operon elements are used today in systems and synthetic biology. In the majority of the cases the gratuitous inducers IPTG or TMG are used. Here we report a systematic comparison of lac promoter induction by TMG and IPTG which focuses on the aspects inducer uptake, population heterogeneity and a potential influence of the transacetylase, LacA. We provide induction curves in E. coli LJ110 and in isogenic lacY and lacA mutant strains and we show that both inducers are substrates of the lactose permease at low inducer concentrations but can also enter cells independently of lactose permease if present at higher concentrations. Using a gfp reporter strain we compared TMG and IPTG induction at single cell level and showed that bimodal induction with IPTG occurred at approximately ten-fold lower concentrations than with TMG. Furthermore, we observed that lac operon induction is influenced by the transacetylase, LacA. By comparing two Plac-gfp reporter strains with and without a lacA deletion we could show that in the lacA(+) strain the fluorescence level decreased after few hours while the fluorescence further increased in the lacA(-) strain. The results indicate that through the activity of LacA the IPTG concentration can be reduced below an inducing threshold concentration-an influence that should be considered if low inducer amounts are used. PMID- 22079753 TI - Do rheumatoid arthritis patients have equal access to treatment with new medicines?: tumour necrosis factor-alpha inhibitors use in four European countries. AB - PURPOSE: To explore the use of the biological tumour necrosis factor alpha (TNFalpha) inhibitors used in the treatment of rheumatoid arthritis as a measure of access to treatment with new medicines. In addition, characteristics both related to national health systems and spending will be assessed to explore possible differences in international utilisation. METHODS: Data from four European countries were included: Ireland, The Netherlands, Norway and Portugal. Annual utilisation rates of TNFalpha inhibitors (2003-2007) were expressed as defined daily doses (DDDs)/1000 inhabitants/day. Qualitative data such as country characteristics, national health policy characteristics, guidelines were obtained from the literature. In addition, interviews were held with leading rheumatologists of each country to put obtained results into (cultural) context. RESULTS: Utilisation of TNFalpha inhibitors varied widely from 0.32 (Portugal) to 1.89 (Norway) DDDs/1000 inhabitants/day (2007). A major driver for the utilisation of TNFalpha inhibitors seemed to be the country's total health expenditure (R(2)=0.81). When the use of TNFalpha inhibitors became more established, the association seemed stronger. Differences in health expenditure were nevertheless not the only determinant of usage. Cultural aspects such as difference in recognition of guidelines also come into play when looking at differences in TNFalpha utilisation between countries. CONCLUSIONS: The prospects of patients receiving TNFalpha inhibitor treatment depend on the country where they are living. In case uniformity of management and treatment would be considered to provide health benefits, the extent and the causes of variation should feature prominently on future public health agendas. PMID- 22079754 TI - Design, synthesis and evaluation of non-urea inhibitors of soluble epoxide hydrolase. AB - Inhibition of soluble epoxide hydrolase (sEH) has been proposed as a new pharmaceutical approach for treating hypertension and vascular inflammation. The most potent sEH inhibitors reported in literature to date are urea derivatives. However, these compounds have limited pharmacokinetic profiles. We investigated non-urea amide derivatives as sEH inhibitors and identified a potent human sEH inhibitor 14-34 having potency comparable to urea-based inhibitors. PMID- 22079755 TI - Maplexins, new alpha-glucosidase inhibitors from red maple (Acer rubrum) stems. AB - Thirteen gallic acid derivatives including five new gallotannins, named maplexins A-E, were isolated from red maple (Acer rubrum) stems. The compounds were identified by spectral analyses. The maplexins varied in number and location of galloyl groups attached to 1,5-anhydro-d-glucitol. The isolates were evaluated for alpha-glucosidase inhibitory and antioxidant activities. Maplexin E, the first compound identified with three galloyl groups linked to three different positions of 1,5-anhydro-d-glucitol, was 20 fold more potent than the alpha glucosidase inhibitory drug, Acarbose (IC(50)=8 vs 160 MUM). Structure-activity related studies suggested that both number and position of galloyls attached to 1,5-anhydro-d-glucitol were important for alpha-glucosidase inhibition. PMID- 22079756 TI - From libraries to candidate: the discovery of new ultra long-acting dibasic beta2 adrenoceptor agonists. AB - Libraries of dibasic compounds designed around the molecular scaffold of the DA(2)/beta(2) dual agonist sibenadet (ViozanTM) have yielded a number of promising starting points that have been further optimised into novel potent and selective target molecules with required pharmacokinetic properties. From a shortlist, 31 was discovered as a novel, high potency, and highly efficacious beta(2)-agonist with high selectivity and a duration of action commensurable with once daily dosing. PMID- 22079757 TI - Discovery of a novel class of aldol-derived 1,2,3-triazoles: potent and selective inhibitors of human cytochrome P450 19A1 (aromatase). AB - The discovery of a novel five-component 1,2,3-triazole-containing pharmacophore that exhibits potent and selective inhibition of aromatase (CYP 450 19A1) is described. All compounds are derived from an initial aldol reaction of a phenylacetate derivative with an aromatic aldehyde. Structure-activity data generated from both syn- and anti-aldol adducts provides initial insights into the requirements for both potency and selectivity. PMID- 22079758 TI - Site of action of a pentapeptide agonist at the glucagon-like peptide-1 receptor. Insight into a small molecule agonist-binding pocket. AB - The development of small molecule agonists for class B G protein-coupled receptors (GPCRs) has been quite challenging. With proof-of-concept that exenatide, the parenterally administered peptide agonist of the glucagon-like peptide-1 (GLP1) receptor, is an effective treatment for patients with diabetes mellitus, the development of small molecule agonists could have substantial advantages. We previously reported a lead for small molecule GLP1 receptor agonist development representing the pentapeptide NRTFD. In this work, we have prepared an NRTFD derivative incorporating a photolabile benzoylphenylalanine and used it to define its site of action. This peptide probe was a full agonist with potency similar to NRTFD, which bound specifically and saturably to a single, distinct site within the GLP1 receptor. Peptide mapping using cyanogen bromide and endoproteinase Lys-C cleavage of labeled wild type and M397L mutant receptor constructs identified the site of covalent attachment of NRTFD within the third extracellular loop above the sixth transmembrane segment (TM6). This region is the same as that identified using an analogous photolabile probe based on secretin receptor sequences, and has been shown in mutagenesis studies to be important for natural agonist action of several members of this family. While these observations suggest that small molecule ligands can act at a site bordering the third extracellular loop to activate this class B GPCR, the relationship of this site to the site of action of the amino-terminal end of the natural agonist peptide is unclear. PMID- 22079759 TI - Synthesis and biological evaluations of novel indenoisoquinolines as topoisomerase I inhibitors. AB - A series of novel indenoisoquinoline derivatives were synthesized. The anticancer activities of these molecules were tested in human cancer cell lines A549, HepG2, and HCT-116. These compounds were also tested for their activity of topoisomerase I (top1) inhibition. Among them, compound 25 was found to be 10-times more potent in cell-killing activity for both cell lines HepG2 and HCT-116 than reported compound 11, with IC(50) of 0.019 and 0.093MUM, respectively. Compound 25 was also found to have stronger top1 inhibition activity than 11 in our inhibition assay. Further in vivo evaluations of compound 25 are in progress and will be reported in due course. PMID- 22079760 TI - Synthesis and evaluation of near-infrared fluorescent sulfonamide derivatives for imaging of hypoxia-induced carbonic anhydrase IX expression in tumors. AB - A series of human carbonic anhydrase (hCA) IX inhibitors conjugated to various near-infrared fluorescent dyes was synthesized with the aim of imaging hypoxia induced hCA IX expression in tumor cells in vitro, ex vivo and in vivo. The resulting compounds were profiled for inhibition of transmembrane hCA IX showing a range of potencies from 7.5 to 116 nM and up to 50-fold selectivity over the cytosolic form hCA II. Some of the compounds also showed inhibition selectivity for other transmembrane forms hCA XII and XIV as well. Compounds incubated in vitro with HeLa cells cultured under normoxic and hypoxic conditions detected upregulation of hCA IX under hypoxia by fluorescence microscopy. A pilot in vivo study in HT-29 tumor bearing mice showed significant accumulation of a fluorescent acetazolamide derivative in tumor tissue with little accumulation in other tissues. Approximately 10% of injected dose was non-invasively quantified in tumors by fluorescence molecular tomography (FMT), demonstrating the promise of these new compounds for quantitative imaging of hCA IX upregulation in live animals. PMID- 22079762 TI - Inhibitory constituents of Nardostachys chinensis on nitric oxide production in RAW 264.7 macrophages. AB - The activity-guided fractionation of the MeOH extract of the rhizomes and roots of Nardostachys chinensis led to the isolation of two new sesquiterpenoids, narchinol B (8) and narchinol C (9), along with 10 known compounds, ursolic acid (1), nardosinone (2), pinoresinol (3), desoxo-narchinol A (4), kanshone B (5), epoxyconiferyl alcohol (6), debilon (7), 4alpha,5-dimethyl-1,3-dioxo 1,2,3,4,4alpha,5,6,7-octahydronaphthalene (10), p-coumaric acid (11), and isoferulic acid (12). Their structures were determined using spectroscopic techniques, which included 1D- and 2D-NMR. Among the isolates, compounds 2, 4, 5, 8 and 9 showed inhibitory activity against LPS-induced NO production with IC(50) values of 4.6-21.6 MUM. PMID- 22079761 TI - The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors. AB - Novel prolylcarboxypeptidase (PrCP) inhibitors with nanomolar IC(50) values were prepared by replacing the previously described dichlorobenzimidazole-substituted pyrrolidine amides with a variety of substituted benzylamine amides. In contrast to prior series, the compounds demonstrated minimal inhibition shift in whole serum and minimal recognition by P-glycoprotein (P-gp) efflux transporters. The compounds were also cell permeable and demonstrated in vivo brain exposure. The in vivo effect of compound (S)-6e on weight loss in an established diet-induced obesity (eDIO) mouse model was studied. PMID- 22079763 TI - Different effects of multiple health status indicators on breast and colorectal cancer screening in a nationally representative US sample. AB - OBJECTIVE: To examine the independent associations between multiple health status indicators and breast and colorectal cancer screening (CRCS) in a national US sample. STUDY DESIGN AND SETTING: Analysis of cross-sectional data from the 2005 National Health Interview Survey (NHIS) involved 5115 men and 7100 women aged 50 years and older. MEASURES: Health status indicators included: self-reported perceived health status, number of chronic conditions, and functional limitation due to a chronic condition. Individuals were considered adherent to CRCS guidelines if they reported having a home-based fecal occult blood test in the past year or endoscopy in the past 10 years. Women were adherent to breast cancer screening guidelines if they reported having a mammogram in the previous 2 years. Statistical analyses were conducted using SUDAAN software to account for the complex sampling of the NHIS survey. Logistic regression was used to examine associations between each of the health status indicators and screening adherence for CRCS and mammography and to calculate estimated screening rates. RESULTS: The three health status indicators were independently and differentially associated with screening adherence. Poor perceived health was associated with lower mammography among women, whereas a greater number of chronic conditions were consistently associated with greater screening. In adjusted analyses, functional limitation was only significantly associated with greater CRCS among women. CONCLUSIONS: Our analyses included three common indicators of health status and provide new evidence of their complex associations with cancer screening. Future studies must examine the mechanisms by which these indicators influence screening recommendations and adherence among older adults over time. PMID- 22079764 TI - New insights into dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p in shuttling of PTS1-receptor Pex5p during peroxisome biogenesis. AB - Peroxisome is a single-membrane organelle in eukaryotes. The functional importance of peroxisomes in humans is highlighted by peroxisome-deficient peroxisome biogenesis disorders such as Zellweger syndrome. Two AAA peroxins, Pex1p and Pex6p, are encoded by PEX1 and PEX6, the causal genes for PBDs of complementation groups 1 and 4, respectively. PEX26 responsible for peroxisome biogenesis disorders of complementation group 8 codes for C-tail-anchored type-II membrane peroxin Pex26p, the recruiter of Pex1p-Pex6p complexes to peroxisomes. Pex1p is targeted to peroxisomes in a manner dependent on ATP hydrolysis, while Pex6p targeting requires ATP but not its hydrolysis. Pex1p and Pex6p are most likely regulated in their peroxisomal localization onto Pex26p via conformational changes by ATPase cycle. Pex5p is the cytosolic receptor for peroxisome matrix proteins with peroxisome targeting signal type-1 and shuttles between the cytosol and peroxisomes. AAA peroxins are involved in the export from peroxisomes of Pex5p. Pex5p is ubiquitinated at the conserved cysteine11 in a form associated with peroxisomes. Pex5p with a mutation of the cysteine11 to alanine, termed Pex5p-C11A, abrogates peroxisomal import of proteins harboring peroxisome targeting signals 1 and 2 in wild-type cells. Pex5p-C11A is imported into peroxisomes but not exported, hence suggesting an essential role of the cysteine residue in the export of Pex5p. PMID- 22079765 TI - Effects of posterior capsule tightness on subacromial contact behavior during shoulder motions. AB - BACKGROUND: Although posterior capsule tightness is believed to cause abnormal contact in the subacromial space, it is not clear whether this tightness changes the contact between the acromion and humeral head. MATERIALS AND METHODS: Nine fresh, frozen cadaveric shoulders were used to measure contact pressure on the coracoacromial arch during passive flexion, abduction, and internal and external rotation at 90 degrees of elevation in the scapular plane, as well as horizontal adduction and abduction. The site where the peak contact pressure occurred was also observed. The posterior capsule in the region from 8 to 10 o'clock in the right shoulder was plicated to simulate posterior capsule tightness. RESULTS: Peak contact pressure significantly increased with the tightened posterior capsule during flexion. Although peak contact pressure on the coracoacromial ligament during internal rotation significantly increased after capsule tightening, there was no significant increase in pressure when considering the entire coracoacromial arch. The angle where the peak contact pressure occurred during flexion was not significantly far from the end range. The site of the peak contact pressure in 7 of 9 shoulders was on the lesser tuberosity during flexion, regardless of the posterior capsule tightness. CONCLUSIONS: Posterior capsule tightness increased contact pressure mainly on the lesser tuberosity during flexion. The peak contact pressure occurred close to the end range of flexion, mainly on the lesser tuberosity. These findings are useful to understand the contribution of posterior capsule tightness to subacromial contact. PMID- 22079766 TI - The relationship between scapular notching and reverse shoulder arthroplasty prosthesis design. AB - BACKGROUND: Inferior scapular notching is a common radiographic complication of reverse shoulder arthroplasty. The purpose of this study is to determine the impact of prosthesis design on the incidence and severity of notching. MATERIALS AND METHODS: Eighty-eight patients (mean age, 72 years) who underwent reverse shoulder arthroplasty with a minimum of 12 months' follow-up (mean, 31 months) were retrospectively reviewed. Patients were grouped based on prosthesis design: Tornier (Stafford, TX, USA) (45%), Zimmer (Warsaw, IN, USA) with a nonretentive liner (35%), and Zimmer with a retentive liner (19%). Notching on final radiographs was graded by use of the Sirveaux classification system and a novel classification system. RESULTS: The incidence of notching was significantly higher with the Tornier prosthesis (92%) compared with the Zimmer prosthesis with nonretentive liners (58%) and retentive liners (71%) (P < .05). The incidence of high-grade notching and the median grade were significantly higher with the Tornier prosthesis compared with the Zimmer prosthesis (P < .05). By use of the novel grading system, there was a higher incidence of notching involving the baseplate with the Tornier prosthesis (68%) compared with the Zimmer prosthesis (33%) (P < .05). The addition of a retentive liner was not associated with greater notching than a nonretentive liner for the Zimmer implant. Diagnosis had no significant influence on notching. CONCLUSIONS: A higher incidence and severity of notching were observed with the Tornier reverse arthroplasty compared with the Zimmer reverse arthroplasty at short-term follow-up. These findings may be because of the different morphology of the polyethylene component and/or differences in glenosphere offset between the prosthetic systems. In addition to surgical technique, consideration should be given to prosthesis design in mitigating the risk of scapular notching. PMID- 22079767 TI - Tensile and shear mechanical properties of rotator cuff repair patches. AB - BACKGROUND: Augmentation of rotator cuff tears aims to strengthen the repair and reduce rerupture, yet studies still report high failure rates. This study determines key mechanical properties of rotator cuff repair patches, including establishing values for toughness and measuring the shear properties of repair patches and human rotator cuff tendons. We hypothesized that different repair grafts would (1) have varying material parameters, and (2) not all have mechanical properties similar to human rotator cuff tendons. MATERIALS AND METHODS: Eight specimens each from the Restore, GraftJacket, Zimmer Collagen Repair, and SportsMesh repair patches were tested to failure in tension and for suture pullout. We assessed ultimate tensile strength, tensile (Young's) modulus, and failure strain. This study also established toughness values and shear data. Storage modulus was calculated using dynamic shear analysis for the patches and 18 samples of normal rotator cuff tendon. RESULTS: We report significant variability in important mechanical properties of repair patches, with the mechanical parameters of the patches diverting variously-and often significantly from values for human rotator cuff tendon. CONCLUSIONS: The repair grafts tested all displayed significant variation in their mechanical properties and had at least some reduced parameters compared with human rotator cuff tendons. This study offers experimentally derived information of value to surgeons when selecting rotator cuff repair grafts. A better understanding of the mechanical suitability of repair grafts for supporting human rotator cuffs is needed if repair patches are to provide a solution for the clinical problem of failure of rotator cuff repairs. PMID- 22079768 TI - Regarding: "Operative versus nonoperative treatment after primary traumatic anterior glenohumeral dislocation: expected-value decision analysis": appropriate assessment of uncertainty. PMID- 22079769 TI - Inferior tilt of the glenoid component does not decrease scapular notching in reverse shoulder arthroplasty: results of a prospective randomized study. AB - HYPOTHESIS: The purpose of this study was to determine if inferior tilt of the glenoid component decreased the amount of radiographic scapular notching after reverse shoulder arthroplasty. A secondary goal was to determine if inferior tilt had any effect on clinical outcome. MATERIALS AND METHODS: A prospective randomized trial of 52 consecutive reverse shoulder arthroplasties performed by 1 surgeon for cuff tear arthropathy was performed. The subjects were randomly assigned to receive a glenoid component with no inferior tilt (control group) or a glenoid component that was inferiorly tilted 10 degrees to protect the inferior glenoid (inferior tilt group). All glenoid components were placed in 3 mm of inferior translation. Radiographic notching was graded at a minimum of 1 year after surgery. Clinical outcomes of the groups were recorded. RESULTS: Follow-up radiographs and data were available for 42 subjects, 20 in the inferior tilt group and 22 in the control group. The experimental groups did not differ significantly in the notch ratings or clinical outcomes. Notching occurred in 15 patients (75%) in the inferior tilt group and in 19 (86%) in the control group. Notching scores were 2 or greater in 10 patients (50%) in the inferior tilt group and in 11 (50%) in the control group. CONCLUSION: Placing the glenoid component with inferior tilt does not reduce the incidence or severity of radiographic scapular notching after reverse shoulder arthroplasty. No clinical differences were observed between the groups. PMID- 22079770 TI - Effects of MDMA and related analogs on plasma 5-HT: relevance to 5-HT transporters in blood and brain. AB - (+/-)-3,4-Methylenedioxymethamphetamine (MDMA) is an illicit drug that evokes transporter-mediated release of serotonin (5-HT) in the brain. 5-HT transporter (SERT) proteins are also expressed in non-neural tissues (e.g., blood), and evidence suggests that MDMA targets platelet SERT to increase plasma 5-HT. Here we tested two hypotheses related to the effects of MDMA on circulating 5-HT. First, to determine if MDMA metabolites might contribute to actions of the drug in vivo, we used in vitro microdialysis in rat blood specimens to examine the effects of MDMA and its metabolites on plasma 5-HT. Second, to determine whether effects of MDMA on plasma 5-HT might be used as an index of central SERT activity, we carried out in vivo microdialysis in blood and brain after intravenous MDMA administration. The in vitro results show that test drugs evoke dose-related increases in plasma 5-HT ranging from two- to sevenfold above baseline, with MDMA and its metabolite, (+/-)-3,4-methylenedioxyamphetamine (MDA), producing the largest effects. The ability of MDMA and related analogs to elevate plasma 5-HT is correlated with their potency as SERT substrates in rat brain synaptosomes. The in vivo results reveal that MDMA causes concurrent increases in extracellular 5-HT in blood and brain, but there are substantial individual differences in responsiveness to the drug. Collectively, our findings indicate that MDMA and its metabolites increase plasma 5-HT by a SERT-dependent mechanism, and suggest the possibility that measures of evoked 5-HT release in blood may reflect central SERT activity. PMID- 22079771 TI - In vitro estrogenic activity of two major compounds from the stem bark of Erythrina lysistemon (Fabaceae). AB - Plant-derived estrogen-like compounds, so called phytoestrogens, are given much attention due to their potential therapeutic use. In our previous work the ethylacetate extract of Erythrina lysistemon stem bark showed estrogenic effects on cell culture systems and ovariectomized Wistar rats. Using classical chromatographic methods, two constituents of Erythrina lysistemon have been isolated, referred to here as compounds 1 (alpinumisoflavone) and 2 (abyssinone V 4'-methyl-ether), and their structures successfully determined using spectroscopic techniques. To test their binding affinity, the ligand binding assay has been used on estrogen alpha receptor, and estrogen beta receptor. Furthermore, transactivation assay in stably or transiently transfected human osteosarcoma (U2OS-estrogen alpha receptor and estrogen beta receptor) cells were used to examine their estrogenic activity. The regulations of some estrogen receptor target genes were also investigated. Both compounds bind to estrogen alpha and beta receptors. They significantly increased luciferase activity in a dose-dependent manner and induced the endogenous estrogen receptor-estrogen response element (ERE) interaction in U2OS-estrogen alpha receptor and estrogen beta receptor cells. In contrast, when co-treated with E2, compound 2 did not antagonize E2 activity in both systems whereas, 1 significantly suppressed E2 activity despite its low binding affinity to estrogen beta receptor. This result suggests a non-competitive mechanism. Both compounds also altered the expression of estrogen receptor target genes such as growth regulation by estrogen in breast cancer 1 (GREB1) and Cyclin D1 in breast cells. These results suggest that compounds 1 and 2 endow estrogenic activity and may be the active principles of Erythrina lysistemon. PMID- 22079772 TI - Synergistic antinociceptive actions and tolerance development produced by morphine-fentanyl coadministration: correlation with MU-opioid receptor internalization. AB - It has been described that coadministration of opioids with low doses of other analgesics can reduce adverse effects and increase antinociception, but combinations of two MU-opioid receptor agonists have been poorly explored. The objective of this work was threefold: 1) to evaluate the antinociceptive combination of i.c.v. morphine and fentanyl at different doses; 2) to compare the antinociception produced by acute or repeated administration of an effective morphine dose (1 MUg) alone, or combined with a low fentanyl dose (1 ng); and 3) to correlate these effects with MU-opioid receptor internalization in periaqueductal gray matter and locus coeruleus. Antinociception was evaluated by the tail-flick test and receptor internalization was analyzed by confocal microscopy in Wistar rats. Drug interactions were examined by administering combinations of opioids in 1:3, 1:1 and 3:1 ratios of their respective ED(50) fractions. For tolerance and internalization studies, animals were i.c.v. injected only once (acute treatment) or twice a day until five administrations were completed. Our results show that morphine and fentanyl have synergistic effects. The combination of 1 ng fentanyl with 1 MUg morphine increases the magnitude and duration of antinociception not only after a single injection, but also after five administrations when tolerance develops to morphine alone. Increased and long-lasting antinociception correlates positively with increased beta-arrestin 2 activity and MU-opioid receptor internalization in periaqueductal gray matter and locus coeruleus. These results suggest that combined administration of morphine and fentanyl increases long-lasting antinociception and beta-arrestin 2 signaling contributes to the combination effects. PMID- 22079773 TI - Opioid challenge evaluation of blockade by extended-release naltrexone in opioid abusing adults: dose-effects and time-course. AB - BACKGROUND: Oral naltrexone's effectiveness as an opioid antagonist has been limited due to poor patient adherence. A long-acting naltrexone formulation may be beneficial. This study evaluated the effects of extended-release injectable naltrexone (XR-NTX), targeted for a one-month duration of action, in blocking opioid agonist challenge effects in humans. METHODS: Outpatient non-dependent opioid abusers (N=27) were randomly assigned to a single double-blind IM administration of 75, 150, or 300 mg XR-NTX. To assess the extent of opioid blockade, hydromorphone challenges (0, 3, 4.5, 6 mg IM in ascending order at 1-h intervals [up to 13.5 mg total]) were given at pretreatment baseline and on days 7, 14, 21, 28, 42, and 56. Opioid blockade was assessed via (1) tolerability of the ascending hydromorphone doses; (2) visual analog scale (VAS) ratings of subjective opioid effects and (3) pupil diameter. Effects on the VAS and pupils were assessed via the slope of the time-action function over ascending hydromorphone doses, with zero slope indicating complete blockade. RESULTS: Blockade of the VAS "any drug effect" response to 3 mg hydromorphone was complete for 14, 21, and 28 days, respectively, for the XR-NTX doses of 75, 150, and 300 mg. Subjective effects were more readily blocked than was pupil constriction. Higher hydromorphone doses produced only modest increases in agonist effects. With the 300 mg XR-NTX dose the slope of VAS responses remained at or near zero for one month even with maximal cumulative hydromorphone dosing. CONCLUSIONS: These data quantify the month-long opioid blockade underlying XR-NTX's efficacy in opioid dependence treatment. PMID- 22079774 TI - Undirected head movements of listeners with asymmetrical hearing impairment during a speech-in-noise task. AB - It has long been understood that the level of a sound at the ear is dependent on head orientation, but the way in which listeners move their heads during listening has remained largely unstudied. Given the task of understanding a speech signal in the presence of a simultaneous noise, listeners could potentially use head orientation to either maximize the level of the signal in their better ear, or to maximize the signal-to-noise ratio in their better ear. To establish what head orientation strategy listeners use in a speech comprehension task, we used an infrared motion-tracking system to measure the head movements of 36 listeners with large (>16 dB) differences in hearing threshold between their left and right ears. We engaged listeners in a difficult task of understanding sentences presented at the same time as a spatially separated background noise. We found that they tended to orient their heads so as to maximize the level of the target sentence in their better ear, irrespective of the position of the background noise. This is not ideal orientation behavior from the perspective of maximizing the signal-to-noise ratio (SNR) at the ear, but is a simple, easily implemented strategy that is often effective in an environment where the spatial position of multiple noise sources may be difficult or impossible to determine. PMID- 22079775 TI - Antiphospohlipid syndrome in obstetrics. AB - Antiphospholipid syndrome is characterised by a variety of clinical and immunological manifestations. The clinical hallmarks of this syndrome are thrombosis and poor obstetric outcomes, including miscarriages, fetal loss and severe pre-eclampsia. The main antiphospholipid antibodies include lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein I. The combination of aspirin and heparin is considered the standard of care for women with antiphospholipid syndrome and embryo-fetal losses; however, aspirin in monotherapy may have a place in women with recurrent early miscarriage. A good benefit-risk ratio of low-molecular-weight heparin in pregnancy thrombosis treatment has been reported. Warfarin must be avoided if possible throughout the first trimester of pregnancy. Adequate pregnancy management of women with antiphospholipid syndrome should include co-ordinated medical-obstetrical care, a close follow-up protocol and a good neonatal unit. Close blood pressure control and early detection of proteinuria, together with Doppler studies of the utero placental circulation should be included in the management protocol. PMID- 22079776 TI - Systematic engineering of 3D pluripotent stem cell niches to guide blood development. AB - Pluripotent stem cells (PSC) provide insight into development and may underpin new cell therapies, yet controlling PSC differentiation to generate functional cells remains a significant challenge. In this study we explored the concept that mimicking the local in vivo microenvironment during mesoderm specification could promote the emergence of hematopoietic progenitor cells from embryonic stem cells (ESCs). First, we assessed the expression of early phenotypic markers of mesoderm differentiation (E-cadherin, brachyury (T-GFP), PDGFRalpha, and Flk1: +/-ETPF) to reveal that E-T+P+F+ cells have the highest capacity for hematopoiesis. Second, we determined how initial aggregate size influences the emergence of mesodermal phenotypes (E-T+P+F+, E-T-P+/-F+, and E-T-P+F-) and discovered that colony forming cell (CFC) output was maximal with ~100 cells per PSC aggregate. Finally, we introduced these 100-cell PSC aggregates into a low oxygen environment (5%; to upregulate endogenous VEGF secretion) and delivered two potent blood-inductive molecules, BMP4 and TPO (bone morphogenetic protein-4 and thrombopoietin), locally from microparticles to obtain a more robust differentiation response than soluble delivery methods alone. Approximately 1.7-fold more CFCs were generated with localized delivery in comparison to exogenous delivery, while combined growth factor use was reduced ~14.2-fold. By systematically engineering the complex and dynamic environmental signals associated with the in vivo blood developmental niche we demonstrate a significant role for inductive endogenous signaling and introduce a tunable platform for enhancing PSC differentiation efficiency to specific lineages. PMID- 22079777 TI - Cholesterol-based anionic long-circulating cisplatin liposomes with reduced renal toxicity. AB - Cholesterol anchored derivatives of 5-Cholestene-3-beta-ol 3-hemisuccinate (CHO HS) and 1-cholesteryl-4-omega-methoxy-polyethylene glycol succinate (CHO-PEG) have been synthesized via esterification and employed at various ratios with di stearoylphosphatidylcholine (DSPC) in the preparation of anionic long-circulating nanoliposmes for cisplatin (CDDP) delivery. In the present study, CHO-HS and CHO PEG were characterized by FTIR and (1)H NMR. The particle size and zeta potential of liposomes were determined by Dynamic lights scattering (DLS). The obtained liposomes have concentratedly distributed nanosizes around 100 nm and proper zeta potentials between -39.7 mV and -3.18 mV and good physical stability in test period of 28 days. Fine morphology of the liposomal vesicles can be observed via transmission electron microscopy (TEM). The CDDP encapsulating percentage of liposomes was 43-94% and loading efficiency was 7.5-29.3%, depending on the presence or absence of CHO-HS and CHO-PEG. In addition, the in vitro drug release behaviors, in vitro cytotoxicity against HeLa cells and 293T cells and in vivo CDDP distribution of CDDP loaded CHO-HS/CHO-PEG liposomes were evaluated. The results suggest that CHO-HS/CHO-PEG nanoliposomes represent a promising strategy for the CDDP delivery as an effective long-circulating drug carrier system which may reduce the acute renal toxicity. PMID- 22079778 TI - The regulation of social recognition, social communication and aggression: vasopressin in the social behavior neural network. AB - Neuropeptides in the arginine vasotocin/arginine vasopressin (AVT/AVP) family play a major role in the regulation of social behavior by their actions in the brain. In mammals, AVP is found within a circuit of recriprocally connected limbic structures that form the social behavior neural network. This review examines the role played by AVP within this network in controlling social processes that are critical for the formation and maintenance of social relationships: social recognition, social communication and aggression. Studies in a number of mammalian species indicate that AVP and AVP V1a receptors are ideally suited to regulate the expression of social processes because of their plasticity in response to factors that influence social behavior. The pattern of AVP innervation and V1a receptors across the social behavior neural network may determine the potential range and intensity of social responses that individuals display in different social situations. Although fundamental information on how social behavior is wired in the brain is still lacking, it is clear that different social behaviors can be influenced by the actions of AVP in the same region of the network and that AVP can act within multiple regions of this network to regulate the expression of individual social behaviors. The existing data suggest that AVP can influence social behavior by modulating the interpretation of sensory information, by influencing decision making and by triggering complex motor outputs. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. PMID- 22079779 TI - Functional states of mandibular movements and synovial pumps of the temporomandibular joint. Is it possible to provide a biomechanically correct replacement for the TMJ? AB - Due to its complexity, there is currently an incomplete understanding of temporomandibular joint (TMJ) function, especially in relation to the morphological interplay of the condyle and the disc as well as the disc, the Os temporale and the lateral pterygoid muscle. This also holds true for synovial flow and synovial pumps, the existence of which we postulate and for which we present a theory of their mechanism. In view of the complexity of mandibular movements and the morphology and function of the TMJ, we need to know how precisely a reconstruction of the TMJ, if necessary, must be adapted to nature. An analysis of the morphology of the functional states of the mandible, as well as the synovial pump system, should at least provide a basis for moulding reconstructions. PMID- 22079781 TI - Delivery of demineralized bone matrix powder using a thermogelling chitosan carrier. AB - Demineralized bone matrix (DBM) powder is widely used for bone regeneration due to its osteoinductivity and osteoconductivity. However, difficulties with handling, its tendency to migrate from graft sites, and lack of stability after surgery can sometimes limit the clinical utility of this material. In this work, the possibility of using a thermogelling chitosan carrier to deliver DBM powder was assessed. The DBM-thermogelling putty improved handling and formed a gel-like composite in situ at body temperature within a clinically relevant time period. The properties of the formed composite, including morphology, porosity, mechanical properties, equilibrium swelling as well as degradability, are significantly influenced by the ratio of DBM to thermogelling chitosan. The in vitro study showed that the alkaline phosphatase activity of C2C12 cells encapsulated in the composite was steadily increased with culture time. The in vivo study showed that increased DBM content in the DBM-thermogelling chitosan induced ectopic bone formation in a nude rat model. The diffusion of growth factor from the DBM-thermogelling chitosan as well as the host-implant interactions are discussed. PMID- 22079782 TI - Preparation of gelatin hydrogels incorporating low-molecular-weight heparin for anti-fibrotic therapy. AB - The objective of this study is to design biodegradable hydrogels for the controlled release of low-molecular-weight heparin (LMWH) and evaluate the biological activity. Gelatin was cationized by chemically introducing ethylene diamine into the carboxyl groups in different conditions to obtain cationized gelatins. The cationized gelatin was mixed with the LMWH in aqueous solution to form the complex. Gelatin, together with the complex of LMWH and cationized gelatin, was dehydrothermally cross-linked for different time periods to prepare the gelatin hydrogel-incorporating complex. The hydrogel-incorporating complex was neither degraded in phosphate-buffered saline solution (PBS) at 37 degrees C nor did it release the LMWH complex. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded to release the LMWH complex. The time profile of hydrogel degradation and the LMWH release depended on the condition of hydrogel cross-linking. The longer the cross-linking time period, the slower the hydrogel degradation and the subsequent LMWH release. The half-life period of LMWH release was in good correspondence with that of hydrogel degradation. It is possible that the LMWH was released as the result of hydrogel degradation. When applied to the mouse model of abdominal membrane fibrosis, the hydrogel system of LMWH release showed a promising anti-fibrotic effect. PMID- 22079783 TI - Growth and development of the root apical meristem. AB - A key question in plant developmental biology is how cell division and cell differentiation are balanced to modulate organ growth and shape organ size. In recent years, several advances have been made in understanding how this balance is achieved during root development. In the Arabidopsis root meristem, stem cells in the apical region of the meristem self-renew and produce daughter cells that differentiate in the distal meristem transition zone. Several factors have been implicated in controlling the different functional zones of the root meristem to modulate root growth; among these, plant hormones have been shown to play a main role. In this review, we summarize recent findings regarding the role of hormone signaling and transcriptional networks in regulating root development. PMID- 22079784 TI - Making leaves. AB - Leaves are determinate organs that develop from the flanks of the shoot apical meristem through founder cell recruitment, establishment of proximodistal, dorsoventral and mediolateral axes, and subsequent growth, expansion and differentiation along these axes. Maintenance of the shoot apical meristem and production of leaves requires balanced partitioning of cells between pluripotent and differentiation fates. Hormones have a significant role in this balance but it is becoming apparent that additional intrinsic and extrinsic inputs influence hormone signalling to control meristem function and leaf initiation. As leaves develop, temporal and spatial regulation of growth and maturation determines leaf shape and complexity. Remarkably genes involved in leaf development in the context of the shoot apical meristem are also involved in elaboration of the leaf shape to generate subtle marginal serrations, more prominent lobes or a dissected compound leaf. Potentially these common regulatory modules represent a fundamental means of setting up boundaries separating discrete zones of growth. Defining gene networks involved in leaf shape variation and exploring interspecies differences between such networks is enabling exciting insight into changes that contribute to natural variation of leaf form. PMID- 22079780 TI - Estrogen neuroprotection and the critical period hypothesis. AB - 17beta-Estradiol (estradiol or E2) is implicated as a neuroprotective factor in a variety of neurodegenerative disorders. This review focuses on the mechanisms underlying E2 neuroprotection in cerebral ischemia, as well as emerging evidence from basic science and clinical studies, which suggests that there is a "critical period" for estradiol's beneficial effect in the brain. Potential mechanisms underlying the critical period are discussed, as are the neurological consequences of long-term E2 deprivation (LTED) in animals and in humans after natural menopause or surgical menopause. We also summarize the major clinical trials concerning postmenopausal hormone therapy (HT), comparing their outcomes with respect to cardiovascular and neurological disease and discussing their relevance to the critical period hypothesis. Finally, potential caveats, controversies and future directions for the field are highlighted and discussed throughout the review. PMID- 22079785 TI - Axis formation in Arabidopsis - transcription factors tell their side of the story. AB - Apical-to-basal auxin flux is a defining feature of land plants and determines their main body axis. How is the axis first set up in the embryo? Recent studies reveal that the establishment of embryonic polarity with the asymmetric first division as well as the separation of shoot and root fates within the proembryo depend on transcriptional regulation in the zygote and early embryo. Although the functional connections need to be better defined, this transcriptional network likely provides the positional information required for initiating the machinery capable of processing the systemic signal auxin in a context-dependent manner. PMID- 22079786 TI - The patterning of epidermal hairs in Arabidopsis--updated. AB - Epidermal hairs of Arabidopsis thaliana emerge in regular spacing patterns providing excellent model systems for studies of biological pattern formation. A number of root-hair and leaf-trichome patterning mutants and tools for cell specific and tissue-specific manipulation of patterning protein activities have been combined in cycles of experimentation and mathematical modelling. These approaches have provided insight into molecular mechanisms of epidermal patterning. During the last two years, endoreplication has, unexpectedly, been found to control cell-fate maintenance during trichome patterning. New genetic interactions between a downstream, positive transcriptional regulator and lateral inhibitors of trichome or non-root-hair fate specification have been uncovered. A lateral inhibitor and a new positive regulator have been identified as major loci affecting trichome patterning in natural Arabidopsis populations. Finally, factors that modify root-hair patterning from the underlying cell layer have been discovered. PMID- 22079787 TI - Stem cell maintenance in shoot apical meristems. AB - Stem cell homeostasis in shoot apical meristems of higher plants is regulated through a dynamic balance between spatial regulation of gene expression, cell growth patterns and patterns of differentiation. Cell-cell communication mediated by both the local factors and long-range signals have been implicated in stem cell homeostasis. Here we have reviewed recent developments on spatio-temporal regulation of cell-cell communication processes with an emphasis on how ubiquitously utilized signals such as plant hormones function with local factors in mediating stem cell homeostasis. We also provide a brief overview of how the activity of ubiquitously utilized epigenetic regulators are modulated locally to orchestrate gene expression. PMID- 22079788 TI - A difference-in-differences analysis of health, safety, and greening vacant urban space. AB - Greening of vacant urban land may affect health and safety. The authors conducted a decade-long difference-in-differences analysis of the impact of a vacant lot greening program in Philadelphia, Pennsylvania, on health and safety outcomes. "Before" and "after" outcome differences among treated vacant lots were compared with matched groups of control vacant lots that were eligible but did not receive treatment. Control lots from 2 eligibility pools were randomly selected and matched to treated lots at a 3:1 ratio by city section. Random-effects regression models were fitted, along with alternative models and robustness checks. Across 4 sections of Philadelphia, 4,436 vacant lots totaling over 7.8 million square feet (about 725,000 m(2)) were greened from 1999 to 2008. Regression-adjusted estimates showed that vacant lot greening was associated with consistent reductions in gun assaults across all 4 sections of the city (P < 0.001) and consistent reductions in vandalism in 1 section of the city (P < 0.001). Regression-adjusted estimates also showed that vacant lot greening was associated with residents' reporting less stress and more exercise in select sections of the city (P < 0.01). Once greened, vacant lots may reduce certain crimes and promote some aspects of health. Limitations of the current study are discussed. Community based trials are warranted to further test these findings. PMID- 22079789 TI - Allogeneic hematopoietic stem cell transplantation for pediatric patients with treatment-related myelodysplastic syndrome or acute myelogenous leukemia. AB - The development of treatment-related myelodysplastic syndrome (tMDS) or treatment related acute myelogenous leukemia (tAML) is a complication that can occur after chemotherapy or radiation therapy. Eighteen patients with a previous malignancy treated at our institution and three patients with a nonmalignant primary tumor received an allogeneic hematopoietic stem cell transplant (HSCT) on the pediatric bone marrow (BM) transplantation service for the treatment of tMDS/tAML over a 15 year period. Five patients proceeded to HSCT without induction chemotherapy. Fourteen patients received high-dose cytarabine according to the Capizzi II regimen as first-line induction therapy with 13 of them achieving complete remission (CR) or refractory anemia (RA) with persistent cytogenetic abnormalities after this treatment. Two patients received an anthracycline-based induction therapy. Conditioning regimens were selected according to previous therapies: 11 patients received busulfan-melphalan-fludarabine (BU-MEL-FLU), which consisted of busulfan (0.8 mg/kg/dose every 6 hours *10 doses), melphalan (70 mg/m(2)/dose * two doses), and fludarabine (25 mg/m(2)/dose * five doses) for cytoreduction; three patients received a total body irradiation (TBI)-containing regimen; seven patients received myeloablative regimens containing busulfan and/or melphalan and/or thiotepa with doses modified for organ toxicity. Sixteen patients received T cell-depleted (TCD) grafts; four patients received unmodified grafts; one patient received a double-unit cord blood transplantation (DUCBT). Donors included HLA-matched (n = 9), or mismatched (n = 3) related donors, or HLA matched (n = 4), or mismatched (n = 4) unrelated donors, or DUCBT (n = 1). Disease status at the time of HSCT was: morphologic and cytogenetic CR (n = 12); RA with positive cytogenetics (n = 6); and refractory disease (n = 3). With a median follow-up of 5.9 years (2.2-15.7 years), the 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire group were 61.1% with 12 patients alive without evidence of either primary disease or tMDS/tAML. The OS and DFS rate for the 11 patients who received the BU-MEL-FLU cytoreduction with TCD grafts was 54.5%. DFS was 65.7% for patients in RA or CR at HSCT compared with 0% for patients with >5% residual marrow blasts (P = .015). Nine patients died; the cause of death was relapse of MDS/AML (n = 4) or primary disease (n = 2), graft-versus-host disease (GVHD; n = 2), and infection (n = 1). Four patients developed grade II to IV acute GVHD. One patient developed localized chronic GVHD. Our results suggest that the strategy of induction with high-dose cytarabine therapy followed by allogeneic stem cell transplantation improves the overall outcome for patients with tMDS/tAML. In addition, the use of a TCD transplantation with BU-MEL-FLU as cytoreduction may decrease the toxicity of transplantation in heavily pretreated patients without an increase in relapse rate. PMID- 22079790 TI - Challenges of treating MRSA in long-term care. AB - Methicillin-resistant Staphylococcus aureus (MRSA) infections are an ongoing problem in long-term care facilities. Frail elderly patients in long-term care settings are at increased risk for developing MRSA infections, and treatment of these infections often involves use of costly antibiotics with significant side effects and drug interactions. Pharmacists need to be knowledgeable in the use and monitoring of these antibiotics so they can assist the facility in managing patients with MRSA infections. PMID- 22079791 TI - Telemedicine: sorting out the benefits and obstacles. AB - Telemedicine (TM)-providing health services and information via a telecommunications device to patients or colleagues separated by distance-holds the promise of improving access to care, diagnosis and assessment, patient monitoring, treatment adherence, and positive health outcomes. TM is still evolving, and numerous obstacles must be overcome before it reaches its full potential. Major obstacles include licensure and reimbursement issues along with the development of TM care standards. While many studies have addressed TM's effectiveness, findings, although positive, are tempered because of small sample size and other methodological problems. Successful TM is clinically driven where a need is first identified and then a TM solution fulfills that clinical need. PMID- 22079792 TI - Development of an antibiogram in a long-term care facility. AB - OBJECTIVE: To create an antibiogram-a profile of an organism's susceptibility/resistance to a panel of antibiotics- for a long-term care facility to assess the prevalence of resistance of bacteria present at the facility. DESIGN: Retrospective analysis of culture and sensitivity data from July 1, 2009, through June 30, 2010. SETTING: A long-term care facility in Huntsville, Alabama. PATIENTS AND PARTICIPANTS: Residents of the long-term care facility that had one or more culture and sensitivity test performed. MAIN OUTCOME MEASURE: Susceptibility of bacteria to each antimicrobial tested. RESULTS: Results were compiled and reported according to the Clinical and Laboratory Standards Institute Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data. The most commonly seen bacteria in our long-term care facility were Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. Resistance rates for these bacteria were high and included the presence of methicillinresistant S. aureus and extended-spectrum beta-lactamase producing bacteria. CONCLUSION: Resistance rates were high among all organisms reported. This poses a serious threat to the health care team's ability to effectively treat residents of this facility. Development of an antibiogram to assist physicians in antimicrobial selection will be beneficial in helping evaluate trends in drug resistance to current available treatments. Implementing clinical pathways for empiric treatment of infections could improve the ability to provide consistent treatment for all residents in the facility. PMID- 22079793 TI - Alcohol, medications, and the older adult. AB - Late-onset alcoholism is a common occurrence in older adults and may be a consequence of life-changing events such as retirement, declining health, loss of independence, or loss of a loved one. Alcohol use and misuse often go unrecognized. Alcohol use can cause significant drug interactions and exacerbate underlying disease. Because of physiologic changes in older adults, alcohol pharmacokinetics and pharmacodynamics may be altered and contribute to adverse alcohol-induced clinical consequences. We report on an elderly man who may have had unrecognized alcohol-induced drug interactions, falling, and exacerbation of heart failure. Following a fall, he was admitted to the hospital. After discharge, the man and his wife relocated to an assisted living facility and he abstained from alcohol. Four months later the man received a prescription for a glass of wine or two with dinner; one week later after two glasses of wine, a dose of lorazepam was given. Later that evening the patient fell and suffered a subdural hematoma. The effects of alcohol in older adults are discussed. PMID- 22079794 TI - Discontinuation of unnecessary medications in older adults. AB - OBJECTIVE: Identifying and managing the use of medications that may be discontinued is a daunting task for the health care team, especially for the consultant pharmacist. This article discusses a framework to evaluate the risks and benefits of medications. A case-based approach will be employed to demonstrate the application of evidence-based medicine and the challenges that pharmacists face in attempting to discontinue medications in older adults. DATA SOURCES: Medline and Micromedex were used as resources for primary literature as well as drug information. STUDY SELECTION: Studies were identified based on their relevance to the case to demonstrate the importance of applying emerging literature and evidence-based medicine. DATA EXTRACTION: Guidelines on managing osteoporosis as well as diabetes in older adults were used for this case. DATA SYNTHESIS: A structured framework was applied to demonstrate considerations when tackling challenging medication regimens. CONCLUSION: Patient-centered, individualized medication regimens need to be developed and updated based on the needs of the patient as well as the wishes of the family and caregivers. This is a dynamic process that benefits from the consultant pharmacist, who understands the complexity of the medications and is essential to addressing the use of unnecessary medications. PMID- 22079795 TI - Plants used as antidiabetics in popular medicine in Rio Grande do Sul, southern Brazil. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Plants are widely as antidiabetics. The study of these plants is essential because many of them may have undesirable effects, such as acute or chronic toxicity; or their use may even delay or discourage the adoption of the proper and effective treatment. MATERIALS AND METHODS: The present study surveyed the plant species that are popularly used to treat diabetes mellitus in the state of Rio Grande do Sul in southern Brazil. Sixteen ethnobotanical surveys performed in the state were consulted, and the species used to treat diabetes were listed. For species cited in at least two of the studies, scientific data related to antidiabetic activity were searched in the ISI Knowledge database. The scientific binomial of each species was used as keywords, and data found in review papers were also included. RESULTS: A total of 81 species in 42 families were mentioned; the most important families were Asteraceae and Myrtaceae. Twenty eight species were cited at least twice as being used to treat diabetes in the state. For 11 of these, no scientific data regarding antidiabetic activity could be located. The species most frequently mentioned for use with diabetes were Syzygium cumini (Myrtaceae) and Bauhinia forficata (Fabaceae), in 12 studies each, followed by Sphagneticola trilobata (Asteraceae), in six studies; and Baccharis trimera (Asteraceae), Bidens pilosa (Asteraceae), Cynara scolymus (Asteraceae), and Leandra australis (Melastomataceae) in four studies each. Bauhinia forficata and Syzygium cumini have been studied in more detail for antidiabetic activity. CONCLUSIONS: A considerable number of plant species are traditionally used for the treatment of diabetes melitus in the Rio Grande do Sul State. The majority of those plants that have been studied for antidiabetic activity showed promising results, mainly for Bauhinia forficata and Syzygium cumini. However, for most of the plants mentioned, the studies are not sufficient to guarantee the efficacy and safety in the use of these plants in the treatment against diabetes. PMID- 22079796 TI - The level of arabinitol in autistic children after probiotic therapy. AB - OBJECTIVE: The level of D-arabinitol (DA) and the ratio of D-/L-arabinitol (DA/LA) in the urine of children with autism were investigated. The changes in DA/LA after probiotic treatment in urine samples of children with autism were studied. METHODS: DA and LA and the DA/LA ratio were identified by capillary gas chromatography/mass spectrometry in urine before and after the probiotic therapy. RESULTS: The level of DA is significantly higher (P < 0.05) in the urine of autistic children before (A) and after probiotic supplementation (A1) (160.04 +/- 22.88 MUmol/mmol creatinine and 89.53 +/- 37.41 MUmol/mmol creatinine, respectively). Nonetheless, the probiotic supplementation let to a significant decrease in DA and DA/LA and to a significant improvement in ability of concentration and carrying out orders. CONCLUSION: The use of probiotics seems to be helpful in reducing the level of DA and the ratio of DA/LA in the urine of children with autism. PMID- 22079797 TI - Oral administration of docosahexaenoic acid attenuates interleukin-1beta response and clinical course of septic neonates. AB - OBJECTIVE: To analyze cytokine responses and the clinical course of septic neonates orally supplemented with docosahexaenoic acid as well as to evaluate fatty acid incorporation into leukocytes. METHODS: A quasiexperimental study was conducted in neonates who developed sepsis following a surgical procedure. Selected neonates were randomly assigned to receive 100 mg docosahexaenoic acid (G-DHA) daily or olive oil (G-OO) as placebo for 14 d throughout a sepsis episode. At selection (baseline), blood samples were obtained to determine interleukin-1 (IL-1)beta, interleukin-6 (IL-6), and tumor necrosis factor-alpha as well as the leucocyte fatty acid profile. Measurements were repeated at 7 (D7) and 14 d (D14) of follow-up. Within- and between-group comparisons were conducted with parametric statistics after logarithmic transformation. Repeated measurement analyses with a general linear model procedure were used, adjusting according to human milk intake, use of anti-inflammatory drugs, and nutritional status. RESULTS: Sixty-three neonates were included: 29 in G-DHA group and 34 in G-OO group. Although decreases of cytokines during hospitalization were similar in both groups, there was a greater decrease of IL-1beta in the G-DHA group than in the G-OO group after adjusting by confounders (P = 0.028). Leukocyte docosahexaenoic acid increased from 4.96 +/- 2.96 at baseline to 5.52 +/- 3.05 and 5.92 +/- 2.8 at D7 and D14, respectively, in the G-DHA group (P = 0.044). Illness severity was inversely associated with the proportion of docosahexaenoic acid in leukocytes throughout follow-up (P = 0.034). CONCLUSIONS: Oral supplementation with docosahexaenoic acid to neonates attenuates IL-1beta response and the clinical course of sepsis. This may be an additional strategy to further benefit ill neonates even if they are not candidates for parenteral nutrition. PMID- 22079798 TI - Biocatalytic ketone reduction: a green and efficient access to enantiopure alcohols. AB - Chiral secondary alcohols play an important role in pharmaceutical, agrochemical, and chemical industries. In recent years, impressive steps forward have been achieved towards biocatalytic ketone reduction as a green and useful access to enantiopure alcohols. An increasing number of novel and robust enzymes are now accessible as a result of the ongoing progress in genomics, screening and evolution technologies, while process engineering provides further success in areas of biocatalytic reduction in meeting synthetic challenges. The versatile platform of these techniques and strategies offers the possibility to apply high substrate loading and thus to overcome the limitation of low volumetric productivity of usual enzymatic processes which is the bottleneck for their practical application. In addition, the integration of bioreduction with other enzymatic or chemical steps allows the efficient synthesis of more complex chiral products. PMID- 22079799 TI - Development and applications of destruxins: a review. AB - The insecticidal and phytotoxic activities of destruxins (dtxs) have been well studied. The cyclodepsipeptides, which are dtxs mainly isolated from the fungus Metarhizium anisopliae and other fungi, have been well characterized in vitro and in vivo. A succession of important function, such as antitumoral, antiviral, insecticidal, cytotoxic, immunosuppressant, phytotoxic, and antiproliferative effects have been observed. To date, 39 dtxs derivatives have been identified. Dtxs possess a variety of biological activities, including acting as virulence factors for specific insects, a V-ATPase inhibitor that provides a basis for the development of new drug to against osteoporosis, cancer, or biological control agents, etc. Here, we focus on some of the research progress made on understanding dtxs during the last decade, introduce some of the newly identified dtx members, especially from M. anisopliae, and give an overview of the applications of dtxs. Using the dtxs to learn about and moderate biological events has advanced significantly during the past year. We believe that several ongoing dtx application fields may benefit from the reviewed information herein. PMID- 22079800 TI - Novel and potential application of cryopreservation to plant genetic transformation. AB - The world population now is 6.7 billion and is predicted to reach 9 billion by 2050. Such a rapid growing population has tremendously increased the challenge for food security. Obviously, it is impossible for traditional agriculture to ensure the food security, while plant biotechnology offers considerable potential to realize this goal. Over the last 15 years, great benefits have been brought to sustainable agriculture by commercial cultivation of genetically modified (GM) crops. Further development of new GM crops will with no doubt contribute to meeting the requirements for food by the increasing population. The present article provides updated comprehensive information on novel and potential application of cryopreservation to genetic transformation. The major progresses that have been achieved in this subject include (1), long-term storage of a large number of valuable plant genes, which offers a good potential for further development of novel cultivars by genetic transformation; (2), retention of regenerative capacity of embryogenic tissues and protoplasts, which ensures efficient plant regeneration system for genetic transformation; (3), improvement of transformation efficiency and plant regeneration of transformed cells; (4), long-term preservation of transgenic materials with stable expression of transgenes and productive ability of recombinant proteins, which allows transgenic materials to be stored in a safe manner before being analyzed and evaluated, and allows establishment of stable seed stocks for commercial production of homologous proteins. Data provided in this article clearly demonstrate that cryo-technique has an important role to play in the whole chain of genetic transformation. Further studies coupling cryotechnique and genetic transformation are expected to significantly improve development of new GM crops. PMID- 22079801 TI - Glenoid morphology rather than version predicts humeral subluxation: a different perspective on the glenoid in total shoulder arthroplasty. AB - BACKGROUND: Glenoid retroversion is thought be important in shoulder stability before and after shoulder arthroplasty; thus, many authors recommend glenoid reaming to correct retroversion and improve stability. Genetic analysis has revealed that glenoid vault and scapular development are controlled by different genes and environmental factors, resulting in diverse glenoid morphologies. We therefore analyzed the relative contribution of glenoid morphology and version to humeral head position. MATERIALS AND METHODS: We obtained 121 shoulder computed tomography scans preoperatively for shoulder arthroplasty. Humeral subluxation and glenoid version were measured on the axial image at the middle of each glenoid. Glenoid morphology was characterized as biconcave, worn, displaced, dysplastic, angled, or neutral. The strength of the correlation between humeral subluxation, glenoid version, and glenoid morphology was analyzed. RESULTS: Glenoid version did not correlate with humeral subluxation. The highest frequency of posterior subluxation was noted in biconcave glenoids. Shoulders with other glenoid morphologies were more likely to have anterior or central positioning of the humerus. The mean subluxation ratio for biconcave glenoids was 0.56 and was significantly different from all other morphologies (P < .02). DISCUSSION/CONCLUSION: Even in the arthritic shoulder, glenoid orientation does not appear to explain the complex biomechanics of shoulder stability. The causes of humeral head subluxation before and after total shoulder arthroplasty are likely multifactorial and may include static and dynamic soft-tissue forces. The biconcave glenoid deserves more attention at surgery because of the high association with posterior subluxation. PMID- 22079802 TI - Operative versus nonoperative treatment after primary traumatic anterior glenohumeral dislocation. PMID- 22079803 TI - A bootstrapping algorithm to improve cohort identification using structured data. AB - Cohort identification is an important step in conducting clinical research studies. Use of ICD-9 codes to identify disease cohorts is a common approach that can yield satisfactory results in certain conditions; however, for many use-cases more accurate methods are required. In this study, we propose a bootstrapping method that supplements ICD-9 codes with lab results, medications, etc. to build classification models that can be used to identify cohorts more accurately. The proposed method does not require prior information about the true class of the patients. We used the method to identify Diabetes Mellitus (DM) and Hyperlipidemia (HL) patient cohorts from a database of 800 thousand patients. Evaluation results show that the method identified 11,000 patients who did not have DM related ICD-9 codes as positive for DM and 52,000 patients without HL codes as positive for HL. A review of 400 patient charts (200 patients for each condition) by two clinicians shows that in both the conditions studied, the labeling assigned by the proposed approach is more consistent with that of the clinicians compared to labeling through ICD-9 codes. The method is reasonably automated and, we believe, holds potential for inexpensive, more accurate cohort identification. PMID- 22079805 TI - Improved sonolytic hydrolysis of peptides in aqueous solution with addition of 1,4-benzenedithiol. AB - Described here is the sonolytic hydrolysis of peptides achieved by treatment of aqueous solution to which the radical scavenger 1,4-benzenedithiol (1,4-BDT), which has hydrogen donating ability, has been added. Mass spectrometric analysis of the products of sonolytic hydrolysis gave information about amino acid sequence of the peptides without any byproducts. The additive 1,4-BDT improves the sonolytic hydrolysis of peptides in terms of the rate of hydrolysis reaction and the amount of additive required when compared to catechol, a previously reported additive. The sonolytic hydrolysis of peptides differs from both acid hydrolysis and hydrogen atom-induced dissociation named matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD), in characteristics. We propose a mechanistic reaction for the sonolytic hydrolysis of peptides, based on the mechanisms of both acid hydrolysis and MALDI-ISD processes. The sonolytic hydrolysis of peptides upon addition of hydrogen donating radical scavengers can be rationalized via the attachment of a hydrogen atom to the carbonyl oxygen with subsequent hydrolysis. PMID- 22079804 TI - Gravity and the evolution of cardiopulmonary morphology in snakes. AB - Physiological investigations of snakes have established the importance of heart position and pulmonary structure in contexts of gravity effects on blood circulation. Here we investigate morphological correlates of cardiopulmonary physiology in contexts related to ecology, behavior and evolution. We analyze data for heart position and length of vascular lung in 154 species of snakes that exhibit a broad range of characteristic behaviors and habitat associations. We construct a composite phylogeny for these species, and we codify gravitational stress according to species habitat and behavior. We use conventional regression and phylogenetically independent contrasts to evaluate whether trait diversity is correlated with gravitational habitat related to evolutionary transitions within the composite tree topology. We demonstrate that snake species living in arboreal habitats, or which express strongly climbing behaviors, possess relatively short blood columns between the heart and the head, as well as relatively short vascular lungs, compared to terrestrial species. Aquatic species, which experience little or no gravity stress in water, show the reverse - significantly longer heart-head distance and longer vascular lungs. These phylogenetic differences complement the results of physiological studies and are reflected in multiple habitat transitions during the evolutionary histories of these snake lineages, providing strong evidence that heart-to-head distance and length of vascular lung are co-adaptive cardiopulmonary features of snakes. PMID- 22079806 TI - Effect of ultrasound on the kinetics of cation exchange in NaX zeolite. AB - In this study, we focused on the effect of ultrasound on ion exchange kinetics to obtain the Li-, Ca- and Ce-rich NaX zeolite. The results were compared to those obtained from the traditional batch exchange method under similar conditions. Contact time and initial cation concentration (fold equivalent excess) were studied. Ultrasound enhanced the replacement of Na(+) ion with Li(+), Ca(2+) and Ce(3+) ions in the extra-framework of zeolite up to 76%, 72% and 66%, respectively. The intraparticle diffusion is the rate limiting step in the ion exchange for both exchange methods. As compared to the traditional exchange method, the ultrasonic method applied in this study was found to be very effective on the exchange amount at equilibrium. PMID- 22079807 TI - Degradation of amoxicillin in aqueous solution using sulphate radicals under ultrasound irradiation. AB - Degradation of the antibiotics amoxicillin in aqueous solution using sulphate radicals under ultrasound irradiation was investigated. The preliminary studies of optimal degradation methodology were conducted with only oxone (2KHSO(5) . KHSO(4) . K(2)SO(4)), cobalt activated oxone (oxone/Co(2+)), oxone+ultrasonication (oxone/US) and cobalt activated oxone+ultrasonication (oxone/Co(2+)/US). The chemical oxygen demand (COD) removal efficiency were in the order of oxone= 10%. We compared the mortality predictions made by surgeons and the risk model by using the signed-rank test and investigated cases in which there was a significant discrepancy (at least 2-fold) between the two predictions. RESULTS: The observed 30-d/in-hospital and 180-d mortality rates were 6.1% (11/181) and 11.0% (20/181), respectively. The mean operative mortality prediction made by surgeons (12.0% +/- 5.3%) was higher than that made by the risk model (7.5% +/- 8.5%) (P < 0.001). There was significant discrepancy between the surgeon and risk model estimates in 62% (113/181) of cases. In 53% (60/113) of these cases, the surgeon reported having considered risk factors not included in the CICSP model, including (most commonly) possible need for an additional procedure (n = 15), compromised mobility (n = 11), liver disease (n = 9), hematologic or immunologic disease (n = 6), and quality of targets (n = 5). CONCLUSIONS: In high-risk CABG cases, surgeon and CICSP risk estimates often disagreed markedly, partly because some disease entities of concern to surgeons are not included in the risk model. The higher mortality risk estimated by the surgeons is a better reflection of the considerable mortality risk that extends up to 180 days after surgery. PMID- 22079839 TI - Barriers to accessing surgical care in Pakistan: healthcare barrier model and quantitative systematic review. AB - Inadequate access to surgical services results in increased morbidity and mortality from a spectrum of conditions in Pakistan. We employed a modification of Andersen's model of health services utilization and developed a 'Healthcare Barrier Model,' to characterize the barriers to accessing health care in developing countries, using surgical care in Pakistan as a case study. We performed a literature search from MEDLINE, EMBASE, CINAHL, SCOPUS, Global Health Database, and Cochrane Central Register of Controlled Trials, and selected 64 of 3113 references for analysis. Patient-related variables included age (elderly), gender (female), preferential use of alternative health providers (Hakeem, traditional healers, others), personal perceptions regarding disease and potential for treatment, poverty, personal expenses for healthcare, lack of social support, geographic constraints to accessing a health facility, and compromised general health status as it relates to the development of surgical disease. Environmental barriers include deficiencies in governance, the burden of displaced or refugee populations, and aspects of the medicolegal system, which impact treatment and referral. Barriers relating to the health system include deficiencies in capacity (infrastructure, physical resources, human resources) and organization, and inadequate monitoring. Provider-related barriers include deficiencies in knowledge and skills (and ongoing educational opportunities), delays in referral, deficient communication, and deficient numbers of female health providers for female patients. The Healthcare Barrier model addresses this broad spectrum of barriers and is designed to help formulate a framework of healthcare barriers. To overcome these barriers will require a multidisciplinary, multisectoral effort aimed at strengthening the health system. PMID- 22079840 TI - Function of poly (lactic-co-glycolic acid) nanofiber in reduction of adhesion bands. AB - BACKGROUND: In this study, we investigated the anti-adhesive and anti inflammatory effects of electrospun nanofibrous membranes made of polycaprolactone (PCL), poly-L-lactide (PLLA), poly (lactic-co-glycolic acid) (PLGA), and polyethersulfune (PES) in comparison with the oxidized-regenerated cellulose (Interceed). MATERIALS AND METHODS: Using an adhesion induction model in mice, the membranes were sutured between the abdominal wall and peritoneum after surgical operation to reveal the best membrane for prevention of postoperative adhesion bands using two scoring adhesion systems. RESULTS: Compared with other membranes, PLGA, PCL, and Interceed membranes showed a greater ability to reduce adhesions. The lowest level of inflammation in adhesive tissues as well as cell attachment in vitro was detected for PLGA nanofibrous membranes. CONCLUSIONS: These results suggested that in considering the FDA approved polymers, nanofibrous membranes prepared from PLGA exhibited the highest efficacy for the prevention of postoperative adhesion bands and hold promising potential for application as a new anti-adhesive agent. PMID- 22079841 TI - Curcumin protects against ischemia/reperfusion injury in rat skeletal muscle. AB - BACKGROUND: Curcumin has been shown to decrease ischemia-reperfusion (I/R) injury in kidney or brain tissues. In this study, the effects of curcumin were evaluated in skeletal muscle during I/R injury. MATERIALS AND METHODS: Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h ischemia, the clamp of the femoral vessels of animals was taken off and the animal underwent 2 h reperfusion. We measured plasma concentrations of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) using enzyme-linked immunosorbent assay (ELISA). The right gastrocnemius muscle was harvested and immediately stored at -30 degrees C for the assessment of superoxide dismutase (SOD), catalase (CAT) activities, and measurement of glutathione (GSH), malondialdehyde (MDA), and protein oxidation (PO) levels. Curcumin (100 mg/kg), alpha-tocopherol, and normal saline (10 mL /kg1) were administered intraperitoneally 1 h prior reperfusion. RESULTS: Plasma TNF-alpha or IL-1beta levels increased significantly in I/R group. The plasma levels of these proinflammatory cytokines were reduced in curcumin group. Muscle tissues of I/R groups revealed significantly higher antioxidant enzyme (superoxide dismutase, glutathione peroxidase, catalase) activities, and increased levels of malondialdehyde, nitric oxide, and protein carbonyl content compared with the SHAM group. Levels of these parameters in muscle revealed significant reductions in the I/R + curcumin group compared witho the I/R group. Curcumin has more potent antioxidant activity than vitamin E in the skeletal muscle I/R. CONCLUSION: In this study, protective effects of curcumin against skeletal muscle ischemia-reperfusion injury have been revealed. We underscore the necessity of human studies with curcumin that would be hypothetically beneficial preventing skeletal muscle I/R injury. PMID- 22079842 TI - Direct measurement of blood flow in microvessels grown in Matrigel in vivo. AB - BACKGROUND: The Matrigel assay provides a versatile platform to examine vessel growth. Similarly, the microsphere method is used extensively in laboratory animals to measure tissue-specific blood flow. However, microsphere models have not been used with Matrigel to study angiogenesis in live animals. The goal of this study was to develop a novel technique to directly measure blood flow with microspheres in vessels grown in Matrigel in vivo. METHODS: In calves (n = 10, 110 +/- 5 kg), 5 mL of Matrigel was injected subcutaneously. After 10 d, a percutaneous cardiac catheterization was performed. Fluorescent-labeled 15 MUm microspheres were injected into the left ventricular chamber to distribute throughout the body based on systemic blood flow patterns. Afterwards, Matrigel plugs were removed, and animals were recovered. Flow cytometry was used to count microspheres and quantify blood flow within the plug. FITC-conjugated isolectin B4 staining was performed to quantify Matrigel capillary density. Flow cytometry was performed to quantify circulating plasma CD34(+) cells. Linear regressions were used to determine relationships between Matrigel blood flow, Matrigel capillary density, and plasma CD34(+) cells. RESULTS: Over 10 d, small-caliber vessels grew into subcutaneous Matrigel plugs. Microspheres lodged throughout the plug and indicated that newly grown vessels in the Matrigel were functional and able to accommodate blood flow. Modest associations between Matrigel blood flow, Matrigel capillary density, and circulating plasma CD34(+) cells were noted. CONCLUSION: This method provides a novel and cost-effective technique to measure blood flow within vessels grown in Matrigel in vivo. PMID- 22079843 TI - Protective effects of lycopene on cerulein-induced experimental acute pancreatitis in rats. AB - BACKGROUND: The purpose of our study was to evaluate the protective effect of the strong antioxidant and anti-inflammatory agent, lycopene, on oxidative stress in a rat model of cerulein-induced acute edematous pancreatitis. METHODS: Sprague Dawley rats were pretreated with lycopene (50 mg/kg, i.p.) or saline 15 min before cerulein was given 20 MUg/kg (i.p.) at 1-h intervals within 4 h. Twelve hours after cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and proinflammatory cytokines (TNF-alpha and IL-1beta). Pancreatic tissues were taken for the determination of tissue glutathione (GSH) and malondialdehyde (MDA) levels, Na(+)/K(+)-ATPase, and myeloperoxidase (MPO) activities. Tissue samples were also examined histologically. RESULTS: Acute pancreatitis caused significant decrease in tissue GSH levels and Na(+)/K(+)-ATPase activity, while pancreatic MDA levels and MPO activity were increased. Furthermore, TNF-alpha, IL-1beta, and amylase lipase levels were also significantly increased. On the other hand, lycopene pretreatment reserved all these biochemical indices as well as histopathologic alterations that were induced by cerulein. CONCLUSIONS: According to the results, lycopene protects the pancreatic tissues from oxidative damage induced by cerulein, and this effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation. These results suggest that high dietary intake of tomatoes may have protective effects against acute pancreatitis. PMID- 22079844 TI - The ultrastructure of the fascia lata in hernia patients and healthy controls. AB - BACKGROUND: Current research data indicate that a hernia is a manifestation of a generalized polyethiological connective tissue pathology. The goal of this study was to demonstrate ultrastructural differences in tissues distant from the hernial defect. MATERIALS AND METHODS: Biopsy specimens harvested upon thigh surgery from 12 males aged 25-65 y were compared. Seven of these men had an inguinal hernia or a history thereof. Scanning electron microphotograms taken at a magnification of 50* were analyzed with the use of Image J software. For every patient, 100 thickness measurements were performed of the fibrous elements (cross sections) visible in five consecutive photograms. The person performing the measurements had no means of identifying the patient from whom the specimen had been harvested. RESULTS: The authors have found the thickness of the fibers to fall in the range from 23.441 u (ImageJ intrinsic units) to 94.878 u in the hernia group and 22.067 u to 303.681 u for the control group. A statistically significant difference was found between the mean values of thickness measurements of the fibrous elements in the study and control groups. CONCLUSIONS: The study has shown that in patients with an inguinal hernia, the mean diameter of fibers within the fascia lata is significantly smaller. This appears to indicate that the process is generalized and that one can expect the structural alterations to occur within the connective tissue of the entire organism. The authors speculate that they may result from a combination of external and internal factors. PMID- 22079845 TI - A decision model of therapy for potentially resectable pancreatic cancer. AB - BACKGROUND: Optimal treatment for potentially resectable pancreatic cancer is controversial. Resection is considered the only curative treatment, but neoadjuvant chemoradiotherapy may offer significant advantages. MATERIALS AND METHODS: We developed a decision model for potentially resectable pancreatic cancer. Initial therapeutic choices were surgery, neoadjuvant chemoradiotherapy, or no treatment; subsequent decisions offered a second intervention if not prohibited by complications or death. Payoffs were calculated as the median expected survival. We gathered evidence for this model through a comprehensive MEDLINE search. One-way sensitivity analyses were performed. RESULTS: Neoadjuvant chemoradiation is favored over initial surgery, with expected values of 18.6 and 17.7 mo, respectively. The decision is sensitive to the probabilities of treatment mortality and tumor resectability. Threshold probabilities are 7.0% mortality of neoadjuvant chemoradiotherapy, 69.2% resectability on imaging after neoadjuvant therapy, and 73.7% resectability at exploration after neoadjuvant therapy, 92.2% resectability at initial resection, and 9.9% surgical mortality following chemoradiotherapy. The decision is sensitive to the utility of time spent in chemoradiotherapy, with surgery favored for utilities less than 0.3 and 0.8, for uncomplicated and complicated chemoradiotherapy, respectively. CONCLUSIONS: The ideal treatment for potentially resectable pancreatic cancer remains controversial, but recent evidence supports a slight benefit for neoadjuvant therapy. Our model shows that the decision is sensitive to the probability of tumor resectability and chemoradiation mortality, but not to rates of other treatment complications. With minimal benefit of one treatment over another based on survival alone, patient preferences will likely play an important role in determining best treatment. PMID- 22079846 TI - MG132 alleviates liver injury induced by intestinal ischemia/reperfusion in rats: involvement of the AhR and NFkappaB pathways. AB - BACKGROUND: MG132 is a potent antioxidant and has been reported to play a protective role in ischemia/reperfusion (I/R) of many organs. Recent studies have shown that the Aryl hydrocarbon receptor (AhR) may play a beneficial role in I/R of many organs and an AhR agonist has been implicated in an anti-inflammatory role. MG132 might function as an AhR agonist through proteasome inhibition, possibly through the inhibition of NFkappaB. Herein, we hypothesized that MG132 may play a protective role in liver injury induced by intestinal I/R and we analyzed the expression behavior of AhR and NFkappaB to determine whether the two factors play a role in intestinal I/R. MATERIALS AND METHODS: Thirty-two Sprague Dawley rats were divided into four groups: control, I/R, MG132 control, and MG132 pretreatment. The I/R and MG132 pretreatment groups were subjected to mesenteric arterial ischemia for 1 h and reperfusion for 3 h. The control and MG132 control groups underwent surgical preparation including isolation of the superior mesenteric artery (SMA) without occlusion. The MG132 control and MG132 pretreatment groups were subjected to intraperitoneal administration of 0.5 mg/kg MG132 30 min before surgery. We collected serum specimens to measure TNF-alpha, IL-6, liver tissue levels of malondialdehyde (MDA), AhR, and cyp1a2; NFkappaB, IkappaBalpha, and ICAM-1 were also tested. Histologic changes of liver and intestine were subsequently evaluated. RESULTS: Compared with the control group, significant increases in MDA, NFkappaB, and ICAM-1 levels were accompanied by decreases in AhR, cyp1a2, and IkappaBalpha expression in the liver in the I/R group, which is consistent with liver and intestinal tissue injury. MG132 blocked the alterations of the indicators above. There were no changes in the MG132 control group compared with the control group in the indicators above. CONCLUSIONS: This study demonstrated that MG132 has a significant effect in protection against liver injury induced by intestinal I/R, which may be due to modulation of the AhR and NFkappaB pathways. PMID- 22079847 TI - The feasibility and safety of laparoscopic splenectomy for massive splenomegaly: a comparative study. PMID- 22079848 TI - Pancreatic stump-closed pancreaticojejunostomy can be performed safely in normal soft pancreas cases. AB - BACKGROUND: Pancreatic anastomotic failure remains the main reason for morbidity and mortality after pancreaticoduodenectomy, and there is no existing flawless pancreaticojejunal reconstruction approach to this date, especially for the normal soft pancreas cases. METHODS: We compared a pancreatic stump-closed pancreaticojejunostomy technique (group B; n = 33) with conventional duct-to mucosa fashion (group A; n = 30) retrospectively in 63 normal soft pancreatic texture cases. Some operative related data including postoperative complications, anastomosis time, hospital stay days, mortality rate, and relaparotomy rate were analyzed. RESULTS: There was no difference concerning the incidences of postoperative morbidity, including pancreatic fistula, postpancreatectomy hemorrhage, delayed gastric emptying, intra-abdominal abscess, and remnant pancreatitis between two groups. The differences of anastomosis time, hospitalization days, relaparotomy rate, and mortality rate were also not significant. However, group B patients had a shorter duration (d) for healing of postoperative pancreatic fistula than group A (15.3 +/- 8.5 versus 33.0 +/- 14.1 d, P < 0.05). CONCLUSION: For the normal soft pancreas cases, pancreatic stump closed pancreaticojejunostomy technique is quite safe and convenient according to our experience; ideal clinical results could be achieved with its application in the future. PMID- 22079849 TI - Treatment of primary isolated extramedullary plasmacytoma of esophagus with endoscopic submucosal dissection. PMID- 22079850 TI - Muscle and mortality in cirrhosis. PMID- 22079851 TI - Hospital-based nurses' perceptions of the adoption of Web 2.0 tools for knowledge sharing, learning, social interaction and the production of collective intelligence. AB - BACKGROUND: Web 2.0 provides a platform or a set of tools such as blogs, wikis, really simple syndication (RSS), podcasts, tags, social bookmarks, and social networking software for knowledge sharing, learning, social interaction, and the production of collective intelligence in a virtual environment. Web 2.0 is also becoming increasingly popular in e-learning and e-social communities. OBJECTIVES: The objectives were to investigate how Web 2.0 tools can be applied for knowledge sharing, learning, social interaction, and the production of collective intelligence in the nursing domain and to investigate what behavioral perceptions are involved in the adoption of Web 2.0 tools by nurses. METHODS: The decomposed technology acceptance model was applied to construct the research model on which the hypotheses were based. A questionnaire was developed based on the model and data from nurses (n = 388) were collected from late January 2009 until April 30, 2009. Pearson's correlation analysis and t tests were used for data analysis. RESULTS: Intention toward using Web 2.0 tools was positively correlated with usage behavior (r = .60, P < .05). Behavioral intention was positively correlated with attitude (r = .72, P < .05), perceived behavioral control (r = .58, P < .05), and subjective norm (r = .45, P < .05). In their decomposed constructs, perceived usefulness (r = .7, P < .05), relative advantage (r = .64, P < .05), and compatibility (r = .60,P < .05) were positively correlated with attitude, but perceived ease of use was not significantly correlated (r = .004, P < .05) with it. Peer (r = .47, P < .05), senior management (r = .24,P < .05), and hospital (r = .45, P < .05) influences had positive correlations with subjective norm. Resource (r = .41,P < .05) and technological (r = .69,P < .05) conditions were positively correlated with perceived behavioral control. CONCLUSIONS: The identified behavioral perceptions may further health policy makers' understanding of nurses' concerns regarding and barriers to the adoption of Web 2.0 tools and enable them to better plan the strategy of implementation of Web 2.0 tools for knowledge sharing, learning, social interaction, and the production of collective intelligence. PMID- 22079852 TI - The age-related slowing of voluntary shortening velocity exacerbates power loss during repeated fast knee extensions. AB - Older adults are less fatigable than young during isometric tasks, but this apparent ability to resist fatigue is often abolished when dynamic actions are performed. These findings could indicate that the velocity component of dynamic contractions or the task performed is an important factor in explaining fatigability of older adults. However, it has not been evaluated systematically. The purpose was to investigate the differences in age-related fatigue of the knee extensors in 8 older (73.6+/-3.5 years) and 8 younger (25.1+/-2.6 years) men. Neuromuscular measures were collected at baseline, during and immediately following task termination of three different maximal effort knee extension tasks. On three separate days, participants performed either 30 slow (1.05 rad.s( 1), 60 degrees .s(-1)) or 30 moderate (3.14 rad.s(-1), 180 degrees .s(-1)) isovelocity contractions, or 30 fast unconstrained velocity contractions with a fixed resistance (i.e., 20% maximal voluntary isometric contraction). At baseline, the older men were 25% and 35% less powerful than the younger men for the slow and moderate isovelocity tasks, respectively, but 42% less for the fast unconstrained velocity protocol. At task termination for the slow (old: 53%, young: 53%) and moderate (old: 45%, young: 38%) isovelocity fatigue tasks, power was reduced similarly in both age groups. However, for the fast unconstrained velocity task, power was reduced by a greater extent in older (35%) than the younger men (23%) at task termination. These results highlight that age-related impairments in voluntary shortening velocity exacerbate reductions in power production during repetitive dynamic tasks. Furthermore, the importance of this factor is masked when velocity is constrained (isovelocity) and fatigue is dependent primarily upon slow torque generation. PMID- 22079853 TI - Influence of age and fall type on head injuries in infants and toddlers. AB - Age-based differences in fall type and neuroanatomy in infants and toddlers may affect clinical presentations and injury patterns. OBJECTIVE: Our goal is to understand the influence of fall type and age on injuries to help guide clinical evaluation. DESIGN/SETTING/PARTICIPANTS: Retrospectively, 285 children 0-48 months with accidental head injury from a fall and brain imaging between 2000 and 2006 were categorized by age (infant <=1 year and toddler=1-4 years) and fall type: low (<=3 ft), intermediate (>3 and <10 ft), high height falls (>=10 ft) and stair falls. OUTCOME MEASURES: Clinical manifestations were noted and head injuries separated into primary (bleeding) and secondary (hypoxia, edema). The influence of age and fall type on head injuries sustained was evaluated. RESULTS: Injury patterns in children <4 years varied with age. Despite similar injury severity scores, infants sustained more skull fractures than toddlers (71% vs. 39%). Of children with skull fractures, 11% had no evidence of scalp/facial soft tissue swelling. Of the patients with primary intracranial injury, 30% had no skull fracture and 8% had neither skull fracture nor cranial soft tissue injury. Low height falls resulted in primary intracranial injury without soft tissue or skull injury in infants (6%) and toddlers (16%). CONCLUSIONS: Within a given fall type, age-related differences in injuries exist between infants and toddlers. When interpreting a fall history, clinicians must consider the fall type and influence of age on resulting injury. For young children, intracranial injury is not always accompanied by external manifestations of their injury. PMID- 22079854 TI - Evaluation of pulse wave velocity in systemic lupus erythematosus, rheumatoid arthritis and Behcet's disease. AB - OBJECTIVES: Connective tissue diseases involve characteristic inflammatory lesions in the cardiovascular system, in addition to other systems. The involvement of the cardiovascular system in the course of connective tissue diseases may result in serious morbidity and mortality. Pulse wave velocity which is an indicator of arterial dilatation capacity may predict cardiovascular risk of patients. Pulse wave velocity is inversely proportional to arterial dilatation capacity. Decreased dilatation capacity leads to a reduction in arterial blood pressure and flow dynamics and impairment in coronary perfusion. METHODS: In our study, we examined pulse wave velocity in frequent chronic inflammatory rheumatologic diseases: rheumatoid arthritis, systemic lupus erythematosus, and Behcet's disease. A total of 98 subjects participated in our study including 24 patients with newly diagnosed rheumatoid arthritis (4 males, 20 females; mean age 42.5 +/- 11.5 years), 22 patients with newly diagnosed systemic lupus erythematosus (1 male, 21 females; mean age 35.8 +/- 11.1 years), 33 patients with newly diagnosed Behcet's disease (26 males, 7 females; mean age 32.7 +/- 8.0 years), and 19 healthy subjects in the control group (10 males, 9 females; mean age 36.2 +/- 15.0 years). Aorta pulse wave velocity was determined by Complior Colson (Createch Industrie, Garges les Gonesses, France) device which allowed for pulse wave recording and automated measurement. RESULTS: Pulse wave velocity was higher in rheumatoid arthritis, systemic lupus erythematosus, and Behcet's disease groups compared to the control group. When all variables were included in the regression analysis only age was found to affect pulse wave velocity independently. CONCLUSION: Pulse wave velocity was found to be high in chronic inflammatory connective tissue diseases compared to the control group. However, no difference was found between groups. Age was determined as the most important independent variable in the regression analysis. PMID- 22079855 TI - Low molecular weight heparin versus unfractionated heparin in patients with acute non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention with drug-eluting stents. AB - BACKGROUND: Whether low molecular weight heparin (LMWH) enoxaparin is equivalent to unfractionated heparin (UFH) in patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear. METHODS: A total of 2397 NSTEMI patients who underwent PCI with DES received either LMWH [n=1178, subcutaneous enoxaparin 1 mg/kg, b.i.d., initiated after the patient's arrival and continued until 3-5 days after PCI plus reduced dose of UFH (50-70 U/kg) during PCI] or UFH (n=1219, 24,000U/day infusion, initiated after the patient's arrival and continued until at least 48 h after PCI). The bleeding events and clinical outcomes during in-hospital and at 8 months were compared. RESULTS: Enoxaparin group had similar incidences of cardiac death, total death, and total major adverse cardiac events (MACE) at 8 months compared with UFH group. The incidences of major and minor bleeding events were also similar between the two groups. Multivariable Cox regression analysis showed that enoxaparin group had similar incidences of cardiac death [adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 0.64-2.10, p=0.620], total death (adjusted OR 1.08, 95% CI 0.66-1.76, p=0.760), and total MACE (adjusted OR 0.94, 95% CI 0.69-1.28, p=0.692) at 8 months as compared with UFH group. CONCLUSIONS: Enoxaparin with reduced dose of UFH only during PCI as an adjunctive antithrombotic therapy in NSTEMI patients undergoing PCI with DES was safe and showed comparable 8-month clinical outcomes as compared with UFH alone. PMID- 22079856 TI - Extremely sustained startle-induced clonus: non epileptic motor attacks mimicking clonic seizures in children with encephalopathy. AB - Clonus is a pathological motor pattern characterised by involuntary, rhythmic and brisk muscular contractions in response to peripheral stimuli producing muscle stretching. It indicates pathological involvement of the corticospinal tract and can be considered as a functional spastic movement disorder of variable clinical presentation and duration. We documented severe and prolonged episodes of startle induced clonic attacks associated with severe apnoea, occurring in three infants with severe encephalopathy. The clinical characteristics of such episodes are very similar to those of clonic epileptic seizures. Video-EEG recordings confirmed the non epileptic origin of the episodes. Previous anti-epileptic drug treatment was unsuccessful but myorelaxing drugs produced a dramatic improvement. PMID- 22079857 TI - Functional significance of some particular amino acid residues in Bombyx mori pyridoxal kinase. AB - Pyridoxal kinase (PLK; EC 2.7.1.35) is a key enzyme for vitamin B(6) metabolism in animals. It catalyzes the ATP-dependent phosphorylation of pyridoxal, generating pyridoxal 5'-phosphate, an important cofactor for many enzymatic reactions. Bombyx mori PLK (BmPLK) is 10 or more residues shorter than mammalian PLKs, and some amino acid residues conserved in the PLKs from mammals are not maintained in the protein. Multiple sequence alignment suggested that amino acid residues Thr(47), Ile(54), Arg(88), Asn(121) and Glu(230) might play important roles in BmPLK. In this study, we used a site-directed specific mutagenesis approach to determine the functional significance of these particular amino acid residues in BmPLK. Our results demonstrated that the mutation of Asn(121) to Glu did not affect the catalytic function of BmPLK. The corresponding site-directed mutants of Thr(47) to Asn, Ile(54) to Phe, and Arg(88) to Ile displayed a decreased catalytic efficiency and an elevated Km value for substrate relative to the wild-type value, and no enzyme activity could be detected in mutant of Trp(230) to Glu. Circular dichroism analysis revealed that the mutation of Trp(230) to Glu resulted in mis-folding of the protein. Our results provided direct evidence that residue Trp(230) is crucial to maintain the structural and functional integrity of BmPLK. This study will add to the existing understanding of the characteristic of structure and function of BmPLK. PMID- 22079858 TI - Characterization of periostin isoform pattern in non-small cell lung cancer. AB - INTRODUCTION: The extracellular matrix N-glycoprotein periostin (OSF-2, POSTN) is a major constituent of the desmoplastic stroma around solid tumors. It promotes tumor invasion and metastasis via epithelial-mesenchymal transition (EMT). In this study we investigated periostin expression at both RNA and protein level as well as the expression pattern of its splice isoforms in non-small cell lung cancer (NSCLC). METHODS: Thirty fresh frozen and corresponding formalin-fixed NSCLC tissues (adeno- and squamous cell carcinoma subtype, each n=15) and their matched non-neoplastic tissues were investigated. Periostin mRNA levels were analyzed by quantitative RT-PCR. The EMT-markers periostin and vimentin were analyzed by immunohistochemistry. Laser capture microdissection allowed for analysis of periostin expression in tumor epithelia and stroma, separately. Isoform patterns were investigated by isoform-specific PCR following sequencing in NSCLC, fetal and adult normal lung tissue. RESULTS: The qRT-PCR analysis showed periostin mRNA up-regulation in NSCLC tissue in relation to normal lung, with significantly higher levels in the adeno-compared to the squamous cell subtype (p<0.05). However, protein levels in both tumor epithelia and stroma correlated with squamous cell carcinoma (p<0.001) and larger tumor size (p<0.05). Further, periostin tumor epithelia expression, correlated with higher tumor grade (p<0.05). Sequence analysis detected eight periostin isoforms in fetal lung, but only five in both NSCLC and matched normal lung tissue. Among the eight isoforms, four are new and were labelled 5, 7, 8 and 9. The exclusive presence of isoforms 1 and 9 in fetal tissue suggests splice-specific regulation during lung embryogenesis. Finally, laser capture microdissection demonstrated that both tumor epithelia and stromal cells can be a source of periostin production in NSCLC. CONCLUSIONS: This study represents the first analysis of periostin isoform expression patterns in NSCLC and a characterization of periostin expression in cancer versus stromal cells at both RNA and protein level. PMID- 22079859 TI - Prognostic value of elevated SHIP2 expression in laryngeal squamous cell carcinoma. AB - BACKGROUND AND AIMS: SHIP2, an important negative regulator of insulin signaling, has recently been found to be involved in cancer development and progression. METHODS: In this study, immunohistochemistry was performed to investigate SHIP2 expression in laryngeal squamous cell carcinoma (LSCC) clinical samples. Additionally, the relationship of SHIP2 expression to clinicopathological parameters and prognosis was investigated. RESULTS: SHIP2 expression was detected in 42 (42/54, 77.8%) primary tumor samples but only in three (3/16, 18.75%) adjacent normal samples (p <0.001). Moreover, SHIP2 expression was closely associated with T classification (p = 0.006), clinical stage (I + II/III + IV) (p = 0.001), metastasis (p = 0.002) and recurrence (p = 0.004). Survival analysis revealed that high SHIP2 expression was significantly associated with shorter disease-free and overall survival (both p <0.001). When lymph node status and SHIP2 expression were combined, lymph node-positive patients with SHIP2 overexpression had both poorer disease-free and overall survival than the others (both p <0.001). Multivariate analysis further demonstrated that SHIP2 was an independent prognostic factor for patients with LSCC. CONCLUSIONS: Collectively, these results support the hypothesis that SHIP2 may play a critical role in the initiation and progression of LSCC and may serve as both a prognostic marker and a potential therapeutic target in patients with LSCC. PMID- 22079860 TI - Prevalence of overweight and obesity among preschool children from six cities of northeast China. AB - BACKGROUND AND AIMS: This study was carried out to assess and investigate the prevalence of overweight and obesity among preschool-age children living in northeast China using the World Health Organization (WHO), International Obesity Task Force (IOTF) and Centers for Disease Control and Prevention (CDC) standard criteria and to explore the differences in estimates by using the three reference standards. METHODS: We used data from 8,653 preschool children with an average age of 5.02 years. Weight and height were obtained for each child and body mass index (BMI) was calculated. The prevalence of overweight and obesity was then determined using the CDC, IOTF and WHO guidelines. RESULTS: According to the IOTF reference, 10.98% of the children were overweight and 6.08% were obese. The CDC reference classified 11.27% as overweight and 11.72% as obese. However, with the WHO reference, 10.93% were overweight and 13.81% were obese. There was significant gender difference in the prevalence of overweight and obesity based on the CDC and WHO references. According to age classification, differences in the frequencies of obesity in both boys and girls reached statistical significance using the three references, and the differences were gradually improved from the WHO to CDC and IOTF cut-off points. In this study, the WHO and the CDC references demonstrated a high level of agreement (kappa = 0.89). CONCLUSIONS: The results indicate overweight and obesity prevalence among preschool children in northeast China is comparable to some Western countries. The WHO reported a much higher prevalence of obesity compared to other references. Age, gender and method differences in the prevalence of overweight and obesity suggested a systematic evaluation of the preschool children in China. PMID- 22079861 TI - Iron deficiency is associated with increased levels of blood cadmium in the Korean general population: analysis of 2008-2009 Korean National Health and Nutrition Examination Survey data. AB - INTRODUCTION: We present data from the Korean National Health and Nutrition Examination Survey 2008-2009 on the distribution of blood cadmium levels and their association with iron deficiency in a representative sample of the adult Korean population. METHODS: Serum ferritin was categorized into three levels: low (serum ferritin <15.0 MUg/L), low normal (15.0-30.0 MUg/L for women and 15.0-50.0 for men), and normal (>=30.0 MUg/L for women and >=50.0 for men), and its association with blood cadmium level was assessed after adjustment for various demographic and lifestyle factors. RESULTS: Geometric means of blood cadmium in the low serum ferritin group in women, men, and all participants were significantly higher than in the normal group. Additionally, multiple regression analysis after adjusting for various covariates showed that blood cadmium was significantly higher in the low-ferritin group in women, men, and all participants compared with the normal group. We also found an association between serum ferritin and blood cadmium among never-smoking participants. DISCUSSION: We found, similar to other recent population-based studies, an association between iron deficiency and increased blood cadmium in men and women, independent of smoking status. The results of the present study show that iron deficiency is associated with increased levels of blood cadmium in the general population. PMID- 22079862 TI - Road traffic crashes and the protective effect of road curvature over small areas. AB - Road bends are known to cause traffic crashes, but the hypothesis in this study was that small geographical areas with many road bends have less, not more, road casualties than comparable areas with fewer bends. Data on road crashes involving fatal, serious and slight casualties in 571 wards in Eastern England were examined against four measures of average road curvature (mean angle per bend, cumulative angle per km, number of bends per km and ratio of road distance to straight distance) using regression analysis. Taking account of other risk factors, measures of average road curvature in wards were negatively associated with crash numbers, especially for fatal crashes. The strongest associations were with the cumulative angle turned per km. The results add to evidence suggesting that road casualty risk effects vary with geographical scale. Although individual road bends might be hazardous, frequent bends have a protective effect over a few kilometres of road. PMID- 22079864 TI - Novel (E)-1-(4-methyl-2-(alkylamino)thiazol-5-yl)-3-arylprop-2-en-1-ones as potent antimicrobial agents. AB - New (E)-1-(4-methyl-2-(alkylamino)thiazol-5-yl)-3-arylprop-2-en-1-ones, unsubstituted or carrying fluoro, bromo, methoxy, nitro, methyl and chloro groups on the benzene ring, were synthesized and assayed in vitro for their antimicrobial activity against Gram positive and Gram negative bacteria and fungi. The compounds were very potent towards all tested microorganisms and in most cases their activity was better than that of reference drugs. PMID- 22079863 TI - Photoaffinity labeling of Ras converting enzyme using peptide substrates that incorporate benzoylphenylalanine (Bpa) residues: improved labeling and structural implications. AB - Rce1p catalyzes the proteolytic trimming of C-terminal tripeptides from isoprenylated proteins containing CAAX-box sequences. Because Rce1p processing is a necessary component in the Ras pathway of oncogenic signal transduction, Rce1p holds promise as a potential target for therapeutic intervention. However, its mechanism of proteolysis and active site have yet to be defined. Here, we describe synthetic peptide analogues that mimic the natural lipidated Rce1p substrate and incorporate photolabile groups for photoaffinity-labeling applications. These photoactive peptides are designed to crosslink to residues in or near the Rce1p active site. By incorporating the photoactive group via p benzoyl-l-phenylalanine (Bpa) residues directly into the peptide substrate sequence, the labeling efficiency was substantially increased relative to a previously-synthesized compound. Incorporation of biotin on the N-terminus of the peptides permitted photolabeled Rce1p to be isolated via streptavidin affinity capture. Our findings further suggest that residues outside the CAAX-box sequence are in contact with Rce1p, which has implications for future inhibitor design. PMID- 22079865 TI - Anti-cancer activity of 5-O-alkyl 1,4-imino-1,4-dideoxyribitols. AB - New derivatives of 1,4-dideoxy-1,4-imino-D-ribitol have been prepared and evaluated for their cytotoxicity on solid and haematological malignancies. 1,4 Dideoxy-5-O-[(9Z)-octadec-9-en-1-yl]-1,4-imino-D-ribitol (13, IC(50) ~2 MUM) and its C(18)-analogues (IC(50) <10 MUM) are cytotoxic toward SKBR3 (breast cancer) cells. 13 also inhibits (IC(50) ~8 MUM) growth of JURKAT cells. PMID- 22079866 TI - Photoligation of self-assembled DNA constructs containing anthracene functionalized 2'-amino-LNA monomers. AB - Efficient synthesis of a novel anthracene-functionalized 2'-amino-LNA phosphoramidite derivative is described together with its incorporation into oligodeoxynucleotides. Two DNA strands with the novel 2'-N-anthracenylmethyl-2' amino-LNA monomers can be effectively cross-linked by photoligation at 366 nm in various types of DNA constructs. Successful application of three differently functionalized 2'-amino-LNA monomers in self-assembled higher ordered structures for simultaneous cross-linking and monitoring of assembly formation is furthermore demonstrated. PMID- 22079867 TI - Synthesis and biological effects of some kynurenic acid analogs. AB - The overactivation of excitatory amino acid receptors plays a key role in the pathomechanism of several neurodegenerative disorders and in ischemic and post ischemic events. Kynurenic acid (KYNA) is an endogenous product of the tryptophan metabolism and, as a broad-spectrum antagonist of excitatory amino acid receptors, may serve as a protective agent in neurological disorders. The use of KYNA is excluded, however, because it hardly crosses the blood-brain barrier. Accordingly, new KYNA analogs which can readily cross this barrier and exert their complex anti-excitatory activity are generally needed. During the past 6 years, we have developed several KYNA derivatives, among others KYNA amides. These new analogs included one, N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2 carboxamide hydrochloride (KYNA-1), that has proved to be neuroprotective in several models. This paper reports on the synthesis of 10 new KYNA amides (KYNA-1 KYNA-10) and on the effectiveness of these molecules as inhibitors of excitatory synaptic transmission in the CA1 region of the hippocampus. The molecular structure and functional effects of KYNA-1 are compared with those of other KYNA amides. Behavioral studies with these KYNA amides demonstrated that they do not exert significant nonspecific general side-effects. KYNA-1 may therefore be considered a promising candidate for clinical studies. PMID- 22079868 TI - A rapid, targeted, neuron-selective, in vivo knockdown following a single intracerebroventricular injection of a novel chemically modified siRNA in the adult rat brain. AB - There has been a dramatic expansion of the literature on RNA interference and with it, increasing interest in the potential clinical utility of targeted inhibition of gene expression and associated protein knockdown. However, a critical factor limiting the experimental and therapeutic application of RNA interference is the ability to deliver small interfering RNAs (siRNAs), particularly in the central nervous system, without complications such as toxicity and inflammation. Here we show that a single intracerebroventricular injection of Accell siRNA, a new type of naked siRNA that has been modified chemically to allow for delivery in the absence of transfection reagents, even into differentiated cells such mature neurons, leads to neuron-specific protein knockdown in the adult rat brain. Following in vivo delivery, targeted Accell siRNAs were incorporated successfully into various types of mature neurons, but not glia, for 1 week in diverse brain regions (cortex, striatum, hippocampus, midbrain, and cerebellum) with an efficacy of delivery of approximately 97%. Immunohistochemical and Western blotting analyses revealed widespread, targeted inhibition of the expression of two well-known reference proteins, cyclophilin-B (38-68% knockdown) and glyceraldehyde 3-phosphate dehydrogenase (23-34% knockdown). These findings suggest that this novel procedure is likely to be useful in experimental investigations of neuropathophysiological mechanisms. PMID- 22079869 TI - Enrichment of ANME-1 from Eckernforde Bay sediment on thiosulfate, methane and short-chain fatty acids. AB - The microorganisms involved in sulfate-dependent anaerobic oxidation of methane (AOM) have not yet been isolated. In an attempt to stimulate the growth of anaerobic methanotrophs and associated sulfate reducing bacteria (SRB), Eckernforde Bay sediment was incubated with different combinations of electron donors and acceptors. The organisms involved in AOM coupled to sulfate reduction (ANME-1, ANME-2, and Desulfosarcina/Desulfococcus) were monitored using specific primers and probes. With thiosulfate as sole electron acceptor and acetate, pyruvate or butyrate as the sole electron donor, ANME-1 became the dominant archaeal species. This finding suggests that ANME-1 archaea are not obligate methanotrophs and that ANME-1 can grow on acetate, pyruvate or butyrate. PMID- 22079871 TI - Nocturia in older men. AB - Nocturia is a common and bothersome symptom that impacts on sleep-quality and quality of life. Nocturia often has a multi-factorial etiology which makes thorough assessment of the complaint indispensable. This review summarizes the definition of nocturia, its epidemiology, clinical presentation, pathophysiology, diagnostics, and treatment options with special reference to older men. Nocturia is defined as a nocturnal voiding frequency of two or more, based on impact on quality of life. It is very prevalent in older men. Apart from the negative effects of sleep-disruption, it may be a risk-factor for hip fractures and increased mortality. Most common causes are: nocturnal polyuria, 24-h polyuria, overactive bladder (sometimes due to BPH) and sleep disturbance. A clear understanding of the etiology in the individual patient is indispensable when addressing the various possible causes and co-morbidities. Most important tool for this is the frequency-volume chart, but also patient history, physical examination and serum analysis. For treatment, lifestyle adjustments are often helpful. Medical therapy with 5-alpha reductase inhibitors, alpha-blockers, a combination of the two, or anti-muscarinics, has a limited effect. Most important medical option is desmopressin (arginine vasopressin analogue); however, treatment with this drug is limited to men under 65 years mainly due to the risk of hyponatraemia. PMID- 22079870 TI - Evaluating the unequal-variance and dual-process explanations of zROC slopes with response time data and the diffusion model. AB - We tested two explanations for why the slope of the z-transformed receiver operating characteristic (zROC) is less than 1 in recognition memory: the unequal variance account (target evidence is more variable than lure evidence) and the dual-process account (responding reflects both a continuous familiarity process and a threshold recollection process). These accounts are typically implemented in signal detection models that do not make predictions for response time (RT) data. We tested them using RT data and the diffusion model. Participants completed multiple study/test blocks of an "old"/"new" recognition task with the proportion of targets and the test varying from block to block (.21, .32, .50, .68, or .79 targets). The same participants completed sessions with both speed emphasis and accuracy-emphasis instructions. zROC slopes were below one for both speed and accuracy sessions, and they were slightly lower for speed. The extremely fast pace of the speed sessions (mean RT=526) should have severely limited the role of the slower recollection process relative to the fast familiarity process. Thus, the slope results are not consistent with the idea that recollection is responsible for slopes below 1. The diffusion model was able to match the empirical zROC slopes and RT distributions when between-trial variability in memory evidence was greater for targets than for lures, but missed the zROC slopes when target and lure variability were constrained to be equal. Therefore, unequal variability in continuous evidence is supported by RT modeling in addition to signal detection modeling. Finally, we found that a two-choice version of the RTCON model could not accommodate the RT distributions as successfully as the diffusion model. PMID- 22079872 TI - Oophorectomy for whom and at what age? Primum non nocere. PMID- 22079873 TI - ICDP approach to awareness-raising about children's rights and preventing violence, child abuse, and neglect. AB - In April 2011, the Committee on the Rights of the Child issued the General Comment No. 13 on the right of the child to freedom from all forms of violence. Its Article 19 declares that "protective measures should, as appropriate, include effective procedures for the establishment of social programs to provide necessary support for the child and for those who have the care of the child." One available social program that focuses on providing support for parents, caregivers and children is the International Child Development Program (ICDP), which is presented in this article. The ICDP is designed to influence and improve the quality of contact and relation between the caregivers, usually parents, and children, through the practical application of the eight themes or guidelines for positive interaction. The Convention on the Rights of the Child is a value-based legal document ratified by most countries in the world. This is a significant achievement and it gives a new basis and legitimization for a more humane treatment of children all over the world. Nevertheless, it is important to understand that there is a big gap between a legal document describing ideal conditions for children at a macro-governmental level and its implementation at the microlevel of families and communities. The ICDP is another expression of the same humanitarian spirit as it is encoded in the convention of children' rights. ICDP can be put in practice in any community to create positive conditions for the fulfillment of fundamental children's rights: the right to be protected from violence and to receive the loving care and guidance from the immediate environment which is required to ensure healthy human development. Introducing children's rights is likely to have a major impact on families (and all levels of authorities) if efforts are also made to activate awareness and deeper bonding to children as persons. Without a deep activation of a more humanized and caring relationship to children, provided by social programs such as ICDP, the advocacy for children's rights may become an empty shell without its basis in human realities. PMID- 22079874 TI - Determination of the heterogeneous interactome between Edwardsiella tarda and fish gills. AB - Edwardsiellosis caused by Edwardsiella tarda is a frequent occurrence throughout the world and has resulted in extensive losses in aquaculture. However, information regarding to protein-protein interaction between the pathogenic cells and host is not available although the portal of entry of the pathogen is determined. In this study, fish gill and bacterial pull-down approaches were used to isolate both bacterial outer membrane proteins that bind to gills and fish gill proteins that interact with bacterial cells, respectively. Eight interacting bacterial proteins and twelve interacting fish proteins were obtained. The genes of seven bacterial proteins were cloned and expressed for preparation of antibodies. The prepared antibodies were used to investigate protein-protein interactions between bacterial cells and fish gills. Five heterogeneous protein protein interactions were determined. Moreover, the protective ability of three of the bacterial recombinant proteins, selected at random, was investigated in a mouse model where they showed significant protection. The gill proteins were highly homologous proteins with from humans and other animals where they are known to be involved in host immunity. These findings indicate that the heterogeneous interactome has significantly biological significance. Our results demonstrate a way to determine and understand the heterogeneous interaction between of E. tarda and gills. PMID- 22079875 TI - Femoral tunnel widening after hamstring anterior cruciate ligament reconstruction with bioabsorbable transfix. AB - BACKGROUND: Previous reports have shown that bio-Transfix implants (Arthrex, Naples, Florida) have the possibility of fracture during the early postoperative period. However, to date, there exists no study reporting the radiological and clinical significance of broken bio-Transfix implants. HYPOTHESIS: A broken bio Transfix results in adverse effects, both radiologically and clinically. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Hamstring anterior cruciate ligament (ACL) reconstructions using bio-Transfix in 50 patients with a minimum of 2 years' postoperative follow-up were reviewed. On the anteroposterior (AP) and lateral radiographs, the diameter of the femoral tunnel was measured at the widest diameter and compared with the diameter of the reamer used at surgery. Magnetic resonance imaging (MRI) scans were obtained 6 months postoperatively for all patients to evaluate the condition of bio-Transfix implants. The patients were divided into intact and broken bio-Transfix groups. Postoperative stability evaluations were performed using the Lachman and pivot-shift tests and instrumented laxity testing using the KT-1000 arthrometer. Functional evaluations were performed using the Lysholm score and Tegner activity scale. RESULTS: Follow up MRI scans revealed that the bio-Transfix was broken in 11 and intact in 39 patients. Five implants were broken within the femoral tunnel and 6 were broken outside the femoral tunnel. Two bio-Transfix in the intact group were bent. On the AP and lateral radiographs at 24 months postoperatively, the average diameter of the femoral tunnel in the intact group increased by 13.1% and 17.1%, respectively. In the broken group at 24 months postoperatively, the average diameter of the femoral tunnel increased by 33.6% and 26.5%, respectively. There were significant differences between the 2 groups in the average diameters of the femoral tunnel on the AP radiographs at 24 months postoperatively (P = .000). However, on the lateral radiographs, there were no significant differences between the 2 groups. Postoperative knee stability tests and functional evaluations showed no significant differences between the 2 groups. CONCLUSION: Broken bio-Transfix implants resulted in significant femoral tunnel widening in the coronal plane, although clinical results were not affected. Surgeons should be aware of this phenomenon when selecting a fixation device for hamstring grafts. PMID- 22079876 TI - Therapeutic angiogenesis in patients with severe limb ischemia by transplantation of a combination stem cell product. AB - OBJECTIVE: Angiogenesis involves the interplay of endothelial progenitor cells, pericytes, growth factors, and cellular matrix components. The use of mesenchymal stem cells, which are closely related to pericytes and produce diverse angiogenic growth factors and matrix molecules, seems to be a promising therapeutic modality. We postulate that the use of a combination cell product (mesenchymal stem cells in conjunction with a source of endothelial progenitor cells) is safe and efficient and may optimize the clinical results obtained with the use of endothelial progenitor cells alone. This study assessed whether the intramuscular infusion of a combination cell product represents a viable, effective, and lasting therapeutic modality to improve perfusion in severely ischemic limbs. METHODS: Patients with limb ischemia (n=26) received an intramuscular (gastrocnemius) infusion of the combination cell product in the most ischemic leg and a placebo product in the (less ischemic) contralateral leg. Clinical follow up (months 0.5, 1, 2, and 4 postinfusion) included evaluation of pain-free walking time, ankle-brachial index, perfusion scintigraphy, and quality of life survey. RESULTS: No adverse events occurred after infusion. Efficacy assessment indicated that after cell infusion there was a significant improvement in walking time and ankle-brachial index. In addition, technetium-99m-tetrofosmin scintigraphy demonstrated a significant increase of perfusion in the treated limbs compared with the respective control legs. CONCLUSIONS: This phase II clinical trial shows that the use of a combination cell therapy is safe and effective in increasing blood flow in the ischemic legs of patients with limb ischemia. PMID- 22079877 TI - The nondepolarizing, normokalemic cardioplegia formulation adenosine-lidocaine (adenocaine) exerts anti-neutrophil effects by synergistic actions of its components. AB - OBJECTIVE: A new strategy of normothermic cardioplegia based on the combination of adenosine and lidocaine (adenocaine; Hibernation Therapeutics Global Ltd, Kilquade, Ireland) achieves nondepolarized arrest at normokalemia. Both adenosine and lidocaine independently inhibit neutrophil (polymorphonuclear neutrophil; PMN) activity. However, whether adenocaine exerts greater anti-inflammatory effects is not known. We tested the hypothesis that adenocaine synergistically attenuates PMN functions. METHODS: Superoxide anion (O(2)(-)) generation: Isolated porcine PMNs were primed with cytochalasin B (5 MUg/mL) and activated by N-formylmethionyl-leucyl-phenylalanine (100 nM). O(2)(-) release was quantified using lucigenin-enhanced chemiluminescence. Data were expressed as percent of stimulated control. RESULTS: Both adenosine and lidocaine alone inhibited O(2)(-) production in a dose-dependent manner (adenosine reduced to 67% +/- 8.4% and 21% +/- 2.2% of maximal stimulation at 0.1 and 10 MUmol/L, respectively, lidocaine reduced to 57.9% +/- 18.6% and 28% +/- 5% at 10 and 100 MUmol/L, respectively). Adenocaine further reduced O(2)(-) generation in a synergistic manner. In addition, adenosine alone (0.1-10 MUmol/L) inhibited O(2)(-) generation in primed but not activated PMNs, whereas lidocaine alone (1-100 MUmol/L) inhibited O(2)(-) release in both primed and activated PMNs. Adenocaine further reduced O(2)(-) generation because of inhibition of both priming and activation stages. Both adenosine and lidocaine alone and adenocaine comparably inhibited platelet activating factor-induced CD11 b/c surface expression on PMNs (flow cytometry), but adenocaine further suppressed both CD18 expression (to 47.4% +/- 9.7%) and PMN adherence (to 47.2% +/- 4.3%) compared with adenosine and lidocaine alone. Transmigration of calcein-acetyoxymethyl-labeled PMNs through transwells seeded with cultured coronary artery endothelial cells was reduced comparably by adenosine (to 80.1% +/- 6.7%) and adenocaine (67.3% +/- 9.6%). CONCLUSIONS: Adenocaine suppresses multiple PMN functions including O(2)(-) generation, adhesion molecule expression, PMN adherence, and transmigration. In addition to inducing nondepolarized arrest, adenocaine cardioplegia may exert cardioprotection by inhibiting PMN-mediated inflammatory responses. PMID- 22079878 TI - Specificities of Ricinus communis agglutinin 120 interaction with sulfated galactose. AB - Lectins are used extensively as research tools to detect and target specific oligosaccharide sequences. Ricinus communis agglutinin I (RCA(120)) recognizes non-reducing terminal beta-D-galactose (Galbeta) and its specificities of interactions with neutral and sialylated oligosaccharides have been well documented. Here we use carbohydrate arrays of sulfated Galbeta-containing oligosaccharide probes, prepared from marine-derived galactans, to investigate their interactions with RCA(120). Our results showed that RCA(120) binding to Galbeta1-4 was enhanced by 2-O- or 6-O-sulfation but abolished by 4-O-sulfation. The results were corroborated with competition experiments. Erythrina cristagalli lectin is also a Galbeta-binding protein but it cannot accommodate any sulfation on Galbeta. PMID- 22079879 TI - Hyperglycemia is associated with increased risk of morbidity and mortality after colectomy for cancer. AB - BACKGROUND: The relationship of hyperglycemia to general surgery outcomes is not well-understood. We studied the association of operative day and postoperative day 1 (POD1) blood glucose (BG) with outcomes after open colectomy for cancer. STUDY DESIGN: We retrospectively analyzed the 2000-2005 Veterans Affairs Surgical Quality Improvement Program database, linked with Veterans Affairs Decision Support System BG values. Median BG was categorized as hypoglycemic (<80 mg/dL); normoglycemic (BG 80-120 mg/dL); or mildly (BG 121-160 mg/dL), moderately (BG 161 200 mg/dL), or severely (BG >200 mg/dL) hyperglycemic. The relationship of BG to postoperative outcomes was assessed with multivariable logistic regression. RESULTS: We identified 9,638 colectomies. We excluded 511 procedures for emergency status or preoperative coma, mechanical ventilation, or sepsis. After excluding patients without recorded BG, we analyzed operative day and POD1 BG in 7,576 and 5,773 procedures, respectively. On multivariable analysis, operative day moderate hyperglycemia was associated with surgical site infection (odds ratio = 1.44; 95% CI, 1.10-1.87). POD1 severe hyperglycemia was associated with cardiac arrest (odds ratio = 2.31; 95% CI, 1.08-4.98) and death (odds ratio = 1.97; 95% CI, 1.23-3.15). POD1 mild (odds ratio = 2.20; 95% CI, 1.05-4.60), moderate (odds ratio = 3.44; 95% CI, 1.51-7.84), and severe (odds ratio = 3.94; 95% CI, 1.64-9.58) hyperglycemia and hypoglycemia (odds ratio = 6.74; 95% CI, 1.75-25.97) were associated with myocardial infarction. Associations were similar in diabetic and nondiabetic patients. CONCLUSIONS: Even mild hyperglycemia was associated with adverse outcomes after colectomy, suggesting that a perioperative BG target of 80 to 120 mg/dL, although avoiding hypoglycemia, might be appropriate. Randomized clinical trials are needed to confirm these findings. PMID- 22079880 TI - Ultrasound-guided core biopsy: an effective method of detecting axillary nodal metastases. AB - BACKGROUND: Axillary nodal status is an important prognostic predictor in patients with breast cancer. This study evaluated the sensitivity and specificity of ultrasound-guided core biopsy (Ax US-CB) at detecting axillary nodal metastases in patients with primary breast cancer, thereby determining how often sentinel lymph node biopsy could be avoided in node positive patients. STUDY DESIGN: Records of patients presenting to a breast unit between January 2007 and June 2010 were reviewed retrospectively. Patients who underwent axillary ultrasonography with or without preoperative core biopsy were identified. Sensitivity, specificity, positive predictive value, and negative predictive value for ultrasonography and percutaneous biopsy were evaluated. RESULTS: Records of 718 patients were reviewed, with 445 fulfilling inclusion criteria. Forty-seven percent (n = 210/445) had nodal metastases, with 110 detected by Ax US-CB (sensitivity 52.4%, specificity 100%, positive predictive value 100%, negative predictive value 70.1%). Axillary ultrasonography without biopsy had sensitivity and specificity of 54.3% and 97%, respectively. Lymphovascular invasion was an independent predictor of nodal metastases (sensitivity 60.8%, specificity 80%). Ultrasound-guided core biopsy detected more than half of all nodal metastases, sparing more than one-quarter of all breast cancer patients an unnecessary sentinel lymph node biopsy. CONCLUSIONS: Axillary ultrasonography, when combined with core biopsy, is a valuable component of the management of patients with primary breast cancer. Its ability to definitively identify nodal metastases before surgical intervention can greatly facilitate a patient's preoperative integrated treatment plan. In this regard, we believe our study adds considerably to the increasing data, which indicate the benefit of Ax US-CB in the preoperative detection of nodal metastases. PMID- 22079881 TI - Vibrio salmonicida pathogenesis analyzed by experimental challenge of Atlantic salmon (Salmo salar). AB - Cold-water vibriosis (CV) is a bacterial septicemia of farmed salmonid fish and cod caused by the Gram-negative bacterium Vibrio (Aliivibrio) salmonicida. To study the pathogenesis of this marine pathogen, Atlantic salmon was experimentally infected by immersion challenge with wild type V. salmonicida and the bacterial distribution in different organs was investigated at different time points. V. salmonicida was identified in the blood as early as 2 h after challenge demonstrating a rapid establishment of bacteremia without an initial period of colonization of the host. Two days after immersion challenge, only a few V. salmonicida were identified in the intestines, but the amount increased with time. In prolonged CV cases, V. salmonicida was the dominating bacterium of the gut microbiota causing a release of the pathogen to the water. We hypothesize that V. salmonicida uses the blood volume for proliferation during the infection of the fish and the salmonid intestine as a reservoir that favors survival and transmission. In addition, a motility-deficient V. salmonicida strain led us to investigate the impact of motility in the CV pathogenesis by comparing the virulence properties of the mutant with the wild type LFI1238 strain in both i.p. and immersion challenge experiments. V. salmonicida was shown to be highly dependent on motility to gain access to the fish host. After invasion, motility was no longer required for virulence, but the absence of normal flagellation delayed the disease development. PMID- 22079882 TI - An alternative -1/+2 open reading frame exists within viral N(pro)(1-19) region of bovine viral diarrhea virus SD-1. AB - We previously reported the engineering of an N(pro)-disrupted bovine viral diarrhea virus (BVDV), BSD1-N(pro)/eGFP2A (Fan and Bird, 2008a). Here, we report that BSD1-N(pro)/eGFP2A survives a single nucleotide missing in its C-terminal eGFP region. By using our established reverse genetics system for BVDV, we confirm that the viral mutant is rescued through a -1/+2 ORF initiated in the N(pro)(1-19)/eGFP region of the mutant viral genome. We furthermore uncover that this event occurs in the N(pro)(1-19) region of BVDV strain SD-1. The rescued viral mutant showed dramatic reductions in levels of both viral RNA and viral protein in host cells. Although the mutant is similar to the native strain in viral kinetics, the peak yield of the mutant is decreased dramatically. These findings reveal the existence of an alternative -1/+2 ORF in the N(pro)(1-19) region during the replication of BVDV and open a new avenue to understand the life cycle and pathogenesis of pestiviruses. PMID- 22079883 TI - Effects of amygdala-hippocampal stimulation on interictal epileptic discharges. AB - Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130 Hz) of the amygdala hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined. PMID- 22079884 TI - The impact of the Bacillus subtilis SPB1 biosurfactant on the midgut histology of Spodoptera littoralis (Lepidoptera: Noctuidae) and determination of its putative receptor. AB - SPB1 is a Bacillus subtilis strain producing a lipopeptide biosurfactant. The insecticidal activity of this biosurfactant was evaluated against the Egyptian cotton leaf worm (Spodoptera littoralis). It displayed toxicity with an LC(50) of 251 ng/cm(2). The histopathological changes occurred in the larval midgut of S. littoralis treated with B. subtilis SPB1 biosurfactant were vesicle formation in the apical region, cellular vacuolization and destruction of epithelial cells and their boundaries. Ligand-blotting experiments with S. littoralis brush border membrane vesicles showed binding of SPB1 biosurfactant to a protein of 45 kDa corresponding to its putative receptor. The latter differs in molecular size from those recognized by Bacillus thuringiensis Vip3A and Cry1C toxins, commonly known by their activity against S. littoralis. This result wires the application of B. subtilis biosurfactant for effective control of S. littoralis larvae, particularly in the cases where S. littoralis will develop resistance against B. thuringiensis toxins. PMID- 22079885 TI - Long-term effects of catheter ablation for lone atrial fibrillation: progressive atrial electroanatomic substrate remodeling despite successful ablation. AB - BACKGROUND: Whether curative ablation can prevent progression of the atrial electroanatomic remodeling associated with atrial fibrillation (AF) is not known. OBJECTIVE: The purpose of this study was to determine whether successful radiofrequency ablation (RFA) of AF can prevent progression of the atrial substrate associated with AF. METHODS: Detailed right atrial electroanatomic maps from 11 patients without apparent structural heart disease undergoing RFA of AF at baseline and >=6 months following successful RFA were compared to 11 control patients undergoing electrophysiologic evaluation of supraventricular tachycardia. Bipolar voltage, conduction, effective refractory periods (ERPs), and signal complexity were assessed. RESULTS: At baseline compared with the control group, the AF group demonstrated (1) lower voltage (P <.001); (2) slowed conduction (P = .005); (3) more prevalent complex signals (P <.001); (4) prolonged regional refractoriness (P <.05), and (5) left atrial dilation (P = .01). At 10 +/- 13 month follow-up, the AF group demonstrated the following compared to baseline: (1) lower voltage (P <.05); (2) either no improvement or further slowing of conduction; (3) further prolongation of regional refractoriness (P <.05); and (4) reversal of left atrial dilation (P <.05). CONCLUSION: Patients with lone AF demonstrate evidence of an abnormal atrial substrate at baseline compared to control patients without AF. This substrate does not appear to reverse even after successful catheter ablation. These findings may have implications for long-term outcomes of ablation and for timing of ablative intervention. PMID- 22079886 TI - Mild-to-moderate kidney dysfunction and the risk of sudden cardiac death in the setting of acute myocardial infarction. AB - BACKGROUND: Although end-stage renal disease is known to elevate the risk of sudden cardiac death (SCD), the role of less severe renal impairment in SCD is unclear. OBJECTIVE: The purpose of this study was to examine the association between mild-to-moderate renal impairment and first ischemic ventricular fibrillation (VF). METHODS: Renal function in patients included in the Arrhythmia Genetics in the NEtherlands Study (AGNES) were compared. Cases (n = 337, age 56 +/- 1 year, 80% men) were defined as patients who had survived VF at the time of their first acute ST elevation myocardial infarction (STEMI), and controls (n = 339, age 58 +/- 1 years, 80% men) were defined as those without VF during their first acute STEMI. Estimated glomerular filtration rate (eGFR) at the time of acute STEMI was computed using the 4-variable Modification of Diet in Renal Disease equation. RESULTS: At eGFR less than 105 mL/min, a decrease in eGFR was associated with elevated odds of developing VF during STEMI. The association was essentially flat at eGFR levels >105 mL/min. The lowest eGFR quintile was associated with a >6-fold increase in odds of developing VF compared to the fourth quintile. This association between eGFR and VF at the time of STEMI remained significant after adjusting for potential confounders including electrolyte levels. CONCLUSION: Mild-to-moderate kidney dysfunction is associated with a significantly elevated risk of VF in the setting of acute STEMI. Further studies are needed to investigate the precise mechanisms by which mild kidney function results in VF. PMID- 22079887 TI - PAF and its metabolic enzymes in healthy volunteers: interrelations and correlations with basic characteristics. AB - PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a potent inflammatory mediator, is synthesized via the remodeling and the de novo route, key enzymes of which are acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAF-AT) and DTT-insensitive CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT), respectively. PAF-acetylhydrolase (PAF-AH) and its extracellular isoform lipoprotein-associated phospholipase-A(2) (Lp-PLA(2)) catabolize PAF. This study evaluated PAF levels together with leukocyte PAF-CPT, lyso-PAF-AT, PAF-AH and Lp PLA(2) activities in 106 healthy volunteers. Men had lower PAF levels and higher activity of both catabolic enzymes and lyso-PAF-AT than women (P-values <0.05). Age was inversely correlated with PAF levels in men (r=-0.279, P=0.06) and lyso PAF-AT in women (r=-0.280, P=0.05). In contrast, Lp-PLA(2) was positively correlated with age (r=0.201, P=0.04). Moreover, PAF-CPT was positively correlated with glucose (r=0.430, P=0.002) in women. In addition, Principal Component Analysis revealed three PAF metabolic patterns: (i) increased activities of PAF-CPT and PAF-AH, (ii) increased activities of PAF-CPT and lyso PAF-AT and (iii) increased activity of Lp-PLA(2). The present study underlines the complexity of PAF's metabolism determinants. PMID- 22079888 TI - Arrhythmias: introduction. PMID- 22079889 TI - Synthesis, growth, structural, spectroscopic and optical studies of a semiorganic NLO crystal: zinc guanidinium phosphate. AB - The semi-organic nonlinear optical (NLO) crystal, zinc guanidinium phosphate (ZGuP) has been grown through synthesis between zinc sulphate, guanidine carbonate and orthophosphoric acid from its aqueous solution by slow solvent evaporation technique. Solubility of the synthesized material has been determined for various temperatures using water as solvent. The grown crystal has been characterized by powder X-ray diffraction to confirm the crystal structure. Investigation has been carried out to assign the vibrational frequencies of the grown crystals by Fourier transform infrared spectroscopy technique. (1)H and (13)C FT-NMR have been recorded to elucidate the molecular structure. The optical absorption study confirms the suitability of the crystal for device applications. The second harmonic generation (SHG) efficiency of ZGuP is found to be 1.825 times that of potassium dihydrogen phosphate (KDP). Thermal behavior of the grown crystals has been studied by thermogravimetric and differential thermal analysis. The mechanical properties of the grown crystals have been studied using Vickers microhardness tester. PMID- 22079890 TI - Raman study of the shockwave effect on collagens. AB - The Raman spectra (1800-200 cm(-1)) of isolated dried collagen types I and III were recorded at different times after shockwave (SW) application in aqueous media. SWs were applied in a single session. One week after the SW application the vibrational data analysis indicates changes in the conformation of the collagens; orientational changes are also inferred. During the next three weeks collagens tended to recover the conformation and orientation existing before SW application. PMID- 22079891 TI - Visualizing excipient composition and homogeneity of Compound Liquorice Tablets by near-infrared chemical imaging. AB - This study demonstrated that near-infrared chemical imaging (NIR-CI) was a promising technology for visualizing the spatial distribution and homogeneity of Compound Liquorice Tablets. The starch distribution (indirectly, plant extraction) could be spatially determined using basic analysis of correlation between analytes (BACRA) method. The correlation coefficients between starch spectrum and spectrum of each sample were greater than 0.95. Depending on the accurate determination of starch distribution, a method to determine homogeneous distribution was proposed by histogram graph. The result demonstrated that starch distribution in sample 3 was relatively heterogeneous according to four statistical parameters. Furthermore, the agglomerates domain in each tablet was detected using score image layers of principal component analysis (PCA) method. Finally, a novel method named Standard Deviation of Macropixel Texture (SDMT) was introduced to detect agglomerates and heterogeneity based on binary image. Every binary image was divided into different sizes length of macropixel and the number of zero values in each macropixel was counted to calculate standard deviation. Additionally, a curve fitting graph was plotted on the relationship between standard deviation and the size length of macropixel. The result demonstrated the inter-tablet heterogeneity of both starch and total compounds distribution, simultaneously, the similarity of starch distribution and the inconsistency of total compounds distribution among intra-tablet were signified according to the value of slope and intercept parameters in the curve. PMID- 22079892 TI - To eat or not to eat red meat. A closer look at the relationship between restrained eating and vegetarianism in college females. AB - Previous research has suggested that vegetarianism may serve as a mask for restrained eating. The purpose of this study was to compare the dietary habits and lifestyle behaviors of vegetarians (n=55), pesco-vegetarians (n=28), semi vegetarians (n=29), and flexitarians (n=37), to omnivores (n=91), who do not restrict animal products from their diets. A convenience sample of college-age females completed questionnaires about their eating habits, food choice motivations, and personality characteristics. Results indicated that while vegetarians and pesco-vegetarians were more open to new experiences and less food neophobic, they were not more restrained than omnivores. Rather semi-vegetarians; those who restricted only red meat from their diet, and flexitarians; those who occasionally eat red meat, were significantly more restrained than omnivores. Whereas food choices of semi-vegetarians and flexitarians were motivated by weight control, vegetarians and pesco-vegetarians' food choices were motivated by ethical concerns. By focusing specifically on semi-vegetarian and flexitarian subgroups, more effective approaches can be developed to ensure that their concerns about weight loss do not lead to unhealthful or disordered eating patterns. PMID- 22079894 TI - Drosophila melanogaster S2 cells for expression of heterologous genes: From gene cloning to bioprocess development. AB - In the present review we discuss strategies that have been used for heterologous gene expression in Drosophila melanogaster Schneider 2 (S2) cells using plasmid vectors. Since the growth of S2 cells is not dependent on anchorage to solid substrates, these cells can be easily cultured in suspension in large volumes. The factors that most affect the growth and gene expression of S2 cells, namely cell line, cell passage, inoculum concentration, culture medium, temperature, dissolved oxygen concentration, pH, hydrodynamic forces and toxic metabolites, are discussed by comparison with other insect and mammalian cells. Gene expression, cell metabolism, culture medium formulation and parameters involved in cellular respiration are particularly emphasized. The experience of the authors with the successful expression of a biologically functional protein, the rabies virus glycoprotein (RVGP), by recombinant S2 cells is presented in the topics covered. PMID- 22079893 TI - Genomics in mammalian cell culture bioprocessing. AB - Explicitly identifying the genome of a host organism including sequencing, mapping, and annotating its genetic code has become a priority in the field of biotechnology with aims at improving the efficiency and understanding of cell culture bioprocessing. Recombinant protein therapeutics, primarily produced in mammalian cells, constitute a $108 billion global market. The most common mammalian cell line used in biologic production processes is the Chinese hamster ovary (CHO) cell line, and although great improvements have been made in titer production over the past 25 years, the underlying molecular and physiological factors are not well understood. Confident understanding of CHO bioprocessing elements (e.g. cell line selection, protein production, and reproducibility of process performance and product specifications) would significantly improve with a well understood genome. This review describes mammalian cell culture use in bioprocessing, the importance of obtaining CHO cell line genetic sequences, and the current status of sequencing efforts. Furthermore, transcriptomic techniques and gene expression tools are presented, and case studies exploring genomic techniques and applications aimed to improve mammalian bioprocess performance are reviewed. Finally, future implications of genomic advances are surmised. PMID- 22079895 TI - Biomechanical interpretation of a free-breathing lung motion model. AB - The purpose of this paper is to develop a biomechanical model for free-breathing motion and compare it to a published heuristic five-dimensional (5D) free breathing lung motion model. An ab initio biomechanical model was developed to describe the motion of lung tissue during free breathing by analyzing the stress strain relationship inside lung tissue. The first-order approximation of the biomechanical model was equivalent to a heuristic 5D free-breathing lung motion model proposed by Low et al in 2005 (Int. J. Radiat. Oncol. Biol. Phys. 63 921 9), in which the motion was broken down to a linear expansion component and a hysteresis component. To test the biomechanical model, parameters that characterize expansion, hysteresis and angles between the two motion components were reported independently and compared between two models. The biomechanical model agreed well with the heuristic model within 5.5% in the left lungs and 1.5% in the right lungs for patients without lung cancer. The biomechanical model predicted that a histogram of angles between the two motion components should have two peaks at 39.8 degrees and 140.2 degrees in the left lungs and 37.1 degrees and 142.9 degrees in the right lungs. The data from the 5D model verified the existence of those peaks at 41.2 degrees and 148.2 degrees in the left lungs and 40.1 degrees and 140 degrees in the right lungs for patients without lung cancer. Similar results were also observed for the patients with lung cancer, but with greater discrepancies. The maximum-likelihood estimation of hysteresis magnitude was reported to be 2.6 mm for the lung cancer patients. The first-order approximation of the biomechanical model fit the heuristic 5D model very well. The biomechanical model provided new insights into breathing motion with specific focus on motion trajectory hysteresis. PMID- 22079896 TI - Sugar inhibits the production of the toxins that trigger clostridial gas gangrene. AB - Histotoxic strains of Clostridium perfringens cause human gas gangrene, a devastating infection during which potent tissue-degrading toxins are produced and secreted. Although this pathogen only grows in anaerobic-nutrient-rich habitats such as deep wounds, very little is known regarding how nutritional signals influence gas gangrene-related toxin production. We hypothesize that sugars, which have been used throughout history to prevent wound infection, may represent a nutritional signal against gas gangrene development. Here we demonstrate, for the first time, that sugars (sucrose, glucose) inhibited the production of the main protein toxins, PLC (alpha-toxin) and PFO (theta-toxin), responsible for the onset and progression of gas gangrene. Transcription analysis experiments using plc-gusA and pfoA-gusA reporter fusions as well as RT-PCR analysis of mRNA transcripts confirmed that sugar represses plc and pfoA expression. In contrast an isogenic C. perfringens strain that is defective in CcpA, the master transcription factor involved in carbon catabolite response, was completely resistant to the sugar-mediated inhibition of PLC and PFO toxin production. Furthermore, the production of PLC and PFO toxins in the ccpA mutant strain was several-fold higher than the toxin production found in the wild type strain. Therefore, CcpA is the primary or unique regulatory protein responsible for the carbon catabolite (sugar) repression of toxin production of this pathogen. The present results are analyzed in the context of the role of CcpA for the development and aggressiveness of clostridial gas gangrene and the well known, although poorly understood, anti-infective and wound healing effects of sugars and related substances. PMID- 22079897 TI - The role of proliferation in the regulation of interferon gamma (IFNgamma) expression in foals. AB - Interferon-gamma (IFNgamma) plays an important role against viral and intracellular bacterial infections and its production is deficient in foals. Cellular proliferation provides an opportunity for de novo gene expression, though little is known about its role in regulating IFNgamma expression in foals. While stimulation of foal peripheral blood mononuclear cells (PBMCs) with concanavalin A (ConA) increased the frequency of IFNgamma(+) cells, the overall percentage of IFNgamma(+) cells remained below that of adults. By contrast, the proliferative response of foal PBMC was significantly greater than that of the adults. In foals, IFNgamma production was predominantly associated with those T cells that underwent proliferation, whereas in adults non-dividing cells also produced IFNgamma. While treatment with hydroxyurea inhibited cellular division, it failed to completely block IFNgamma production. This residual IFNgamma production likely represented memory cells as the proportion of these proliferation-independent IFNgamma(+) cells increased with foal age. However, memory cells may not account for all of the IFNgamma production as ConA stimulation likely provided additional signals that can control IFNgamma expression. PMID- 22079899 TI - Ultrastructural study on dynamics of plastids and mitochondria during microgametogenesis in watermelon. AB - Dynamics of plastids and mitochondria during microgametogenesis in watermelon were examined by means of transmission electron microscopy. Plastids are present as proplastids in the microspore and as amyloplasts in the vegetative cell of the bicellular pollen grain, whereas the generative cell is completely devoid of plastids, suggesting that microspore plastids are excluded from the generative cell during the microspore mitotic division. Therefore, watermelon is classified as Lycopersicon type, where plastids exclusion from the generative cell leads to purely maternal plastid inheritance. Mitochondria in the generative cell show noticeable alterations in size and cristae during microgametogenesis. The diameter of mitochondria is about 0.5 MUm in the newly born generative cell, while only about 0.16 MUm in the spindle-shaped generative cell. Numerous cristae are present in mitochondria in the spherical generative cell, but, in contrast, mere two or three cristae retain in the spindle-shaped generative cell in the mature pollen grain. In conclusion, the size and cristae number of mitochondria in the generative cell are reduced significantly during microgametogenesis in watermelon. PMID- 22079898 TI - Megadiverse developing countries face huge risks from invasives. PMID- 22079900 TI - Perception of a self-fitting hearing aid among urban-dwelling hearing-impaired adults in a developed country. AB - A self-fitting hearing aid is a personal amplification device that is designed to be assembled, programmed, and fine-tuned by the user, without the need for additional equipment or professional support. A written description of the device was presented to 80 older adults with a hearing impairment, all of whom were residents of an urban area in a developed country. In response to a structured questionnaire, the majority of participants reported that the self-fitting hearing aid concept was a good idea (83%), would be of personal benefit (60%), and could be managed independently by the user (90%). Overall, half of the participant group agreed with all three statements. Two were uncertain about the concept, but none of the participants rejected it outright. There were no significant differences between the opinions of participants with previous hearing aid experience and those without. Participant responses to open-ended questions revealed that the main benefits of a self-fitting hearing aid were thought to be the ability to self-adjust the device's settings (reported by 33% of participants) and increased convenience (20% of participants). The main drawback, mentioned by 25% of participants, was a preference for professional guidance through the fitting process. These results suggest that the self-fitting hearing aid may present as an alternative product in developed countries for those users who prefer to be in control of the fitting process. PMID- 22079901 TI - Unilateral cervical burn scar deformity elimination with contralateral cervicothoracic flap--a new approach. AB - Unilateral postburn cervical deformity is a severe cosmetic and functional defect and a challenging reconstructive problem. Many flaps have been suggested; however, after surgery, operational scars, located along the anterior neck's middle line, and the flap's skin differ from cervical healthy skin. A small flap resembles a patch. A more effective and safer technique is neck resurfacing with cervicothoracic adipocutaneous flap which had been used by the author in 32 burned patients. The flap's peculiarities are as follows: axis blood circulation via superficial cervical artery perforator; exclusion of platysma (flap is thin and elastic); and undamaged donor site. The mobilized healthy neck's skin with thin fat layer and adipocutaneous layer of the chest wall are elevated as a whole large flap. After scar excision, the cervicothoracic flap is advanced on the wound with tension. As a result of flap tension, the skin of neck's back, thoracic wall, and axilla are displaced to the anterior neck surface covering the donor wound. On an average, 6 cm of the deformed neck anterior surface was restored. No flap loss but only local superficial scar necrosis along the flap's border occurred. The cervical contracture and scar deformity (25 patients) were eliminated in all cases by a single procedure. For complete neck skin restoration, seven patients underwent staged reconstruction using the same technique. Excellent functional and good cosmetic follow-up results were achieved. The proposed technique is easy to plan and perform and yields good results; therefore, the author believes that the contralateral cervicothoracic flap's use is an exclusive option for unilateral cervical contracture and deformity elimination in adults and pediatric patients. PMID- 22079902 TI - Prior thermal injury accelerates endotoxin-induced inflammatory cytokine production and intestinal nuclear factor-kappaB activation in mice. AB - The objective of this study was to increase the understanding of the "second-hit" response in thermal injury. The authors hypothesized that prior thermal injury increases the endotoxin-induced inflammatory response of intestinal mucosa. Mice underwent sham or 25% TBSA scald injury. Seven days after injury, mice were injected with lipopolysaccharide. Blood, jejunum, and colon specimens were obtained at intervals. Serum, jejunal, and colon inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay. Jejunal and colon nuclear factor (NF)-kappaB activation was measured by electrophoretic mobility shift assay. After remote thermal injury, lipopolysaccharide exposure led to an acute increase in serum interleukin (IL)-6, IL-10, and chemokine keratinocyte-derived chemokine (KC) levels. This correlated with lipopolysaccharide-induced increased IL-6 in colon and chemokine KC in the jejunum and colon in burned mice when compared with sham-injured mice. Lipopolysaccharide-induced NF-kappaB activation occurred more rapidly in jejunum and colon from burned mice compared with sham injured mice. Prior thermal injury accelerates lipopolysaccharide-induced inflammatory cytokine production systemically in jejunum and colon. The "second hit" of lipopolysaccharide led to earlier intestinal NF-kappaB activation in burned mice compared with sham-injured mice. These results indicate that there is a heightened inflammatory response by jejunum and colon in response to a "second hit" of lipopolysaccharide after burn injury. PMID- 22079903 TI - Long-term postoperative outcomes after axillary contracture release in children with burns. AB - Children with upper extremity burns frequently develop axillary contractures that can restrict movement. Surgical axillary contracture release is performed to restore function. The purpose of this study is to determine the long-term effects (up to 7 years) of surgical axillary contracture release on upper extremity motion during simulated activities of daily living using three-dimensional motion analysis. Motion analysis was conducted on 10 subjects (9 males and 1 female; 16 axillary contractures; mean age 10 +/- 3 years at baseline; mean TBSA burn 40 +/- 15%) before, 1 year after, and 2 to 7 years (mean 3 +/- 2 years) after axillary contracture release with split-thickness skin graft surgery. Movements were analyzed during three functional tasks including high reach (reaching overhead for an object), hand to head (combing hair), and hand to back pocket (toileting). Two-tailed paired t-tests were used to compare presurgical and postsurgical scores. Surgical release of the axillary contracture increased shoulder mobility and decreased compensatory movements. Improvements were maintained at long-term follow-up. All shoulder movements with the exception of shoulder flexion during the high reach task and shoulder abduction during the hand to back task were not significantly different than normal values at long-term follow-up. Axillary contracture release surgery improves shoulder function in the short and long term. Motion analysis is a modality that may prove valuable in objectively quantifying changes in movement patterns immediately and in subsequent years after burn injury. PMID- 22079904 TI - Computerized insulin infusion programs are safe and effective in the burn intensive care unit. AB - Glucose control has repeatedly been shown to influence favorable outcomes in the surgical intensive care unit (ICU). Intensive insulin therapy has recently been associated with reduced infections complications in burn patients. However, traditional protocols are associated with rates of severe hypoglycemia as high as 19%. Two commercial computer glucose control programs have reported rates of severe hypoglycemia (glucose <50 mg/dl) of 0.6 and 0.4%. Recently, the authors' burn ICU adopted an intensive insulin computer-based protocol created at their institution and already successfully in use in their surgical ICU. The authors hypothesized that their protocol can be used effectively in the burn patient population without an increase risk of severe hypoglycemia. All patients admitted to the burn ICU have blood glucose (BG) values checked routinely. With two consecutive hyperglycemic values >200 mg/dl, patients are placed on a computer based protocol intravenous insulin drip. Once initiated, BGs are tested hourly with adjustments made according to the computer protocol. Values recorded from January to December 2008 were abstracted from the database and analyzed. Thirty one patients were treated using the computer glucose control protocol and 12,699 measurements were performed. There were eight measurements <50 mg/dl (0.07%). Seventy-six percent of values were within the target range of 90 to 150 mg/dl. Few patients had severe hyperglycemia with BG >300 mg/dl (0.2%). There were no adverse events associated with the hypoglycemic episode. The computer-based protocol is more effective than those previously used at the institution and provides safe, reliable results in the burn patients. PMID- 22079905 TI - Inflammatory and protein metabolism signaling responses in human skeletal muscle after burn injury. AB - Severe burn injuries lead to a prolonged hypercatabolic state resulting in dramatic loss of skeletal muscle mass. Postburn muscle loss is well documented but the molecular signaling cascade preceding atrophy is not. The purpose of this study is to determine the response to burn injury of signaling pathways driving muscle inflammation and protein metabolism. Muscle biopsies were collected in the early flow phase after burn injury from the vastus lateralis of a noninjured leg in patients with 20 to 60% TBSA burns and compared with uninjured, matched controls. Circulating levels of proinflammatory cytokines were also compared. Immunoblotting was performed to determine the protein levels of key signaling components for translation initiation, proteolysis, and tumor necrosis factor/nuclear factor kappa B (NFkappaB)and interleukin (IL)-6/STAT3 signaling. Burn subjects had significantly higher levels of circulating proinflammatory cytokines, with no difference in muscle STAT3 activity and lower NFkappaB activity. No differences were found in any translational signaling components. Regarding proteolytic signaling in burn, calpain-2 was 47% higher, calpastatin tended to be lower, and total ubiquitination was substantially higher. Surprisingly, a systemic proinflammatory response 3 to 10 days postburn did not lead to elevated muscle STAT3 or NFkappaB signaling. Signaling molecules governing translation initiation were unaffected, whereas indices of calcium mediated proteolysis and ubiquitin-proteasome activity were upregulated. These novel findings are the first in humans to suggest that the net catabolic effect of burn injury in skeletal muscle (ie, atrophy) may be mediated, at least during the early flow phase, almost entirely by an increased proteolytic activity in the absence of suppressed protein synthesis signaling. PMID- 22079906 TI - Optimal lubricant for split-thickness skin graft harvest. PMID- 22079907 TI - The correlation between time to skin grafting and hypertrophic scarring following an acute contact burn in a porcine model. AB - One sequelae of burn injury remains the development of hypertrophic scarring. This appears more likely when the healing has been prolonged. Early excision of deep dermal burns and subsequent split skin grafting (SSG) may provide a more favorable result. The optimal timing of grafting for deeper dermal burns remains controversial. This study sought to establish evidence for the optimal grafting time using a porcine model. Five Large White female pigs were exposed to four contact burn injuries for duration of 20 seconds at 92 degrees C. Each site was randomized to a treatment arm: dressing only as the control, SSG day 3, SSG day 14, and SSG day 21. Burn wound biopsies were obtained at days 0, 3, 14, 21, and 99 after the burn injury, together with microbiological swabs. Digital photographs were taken to assess scarring using the Vancouver scar scale. All biopsies were subject to histological and immunohistochemical analysis. Vancouver scar scale scores and histopathological analysis indicated that areas grafted on day 3 had the least fibrosis and scarring (P = 0.031). There was a strong correlation between the histological evaluation of the degree of fibrosis and alpha-smooth muscle actin levels (r = .60, P = .014). A greater degree of fibrosis was observed in the presence of infection (P = .028). Sites grafted on day 3 consistently exhibited the best clinical and histological scar outcome. The increased fibrosis observed in delayed grafting may have been be related to progression of burn depth and infection. These results suggest that early grafting of deep dermal burns may be preferential. PMID- 22079908 TI - Pilot testing of a burn prevention teaching tool for Amish children. AB - Burn prevention education for Amish children is warranted as there are unique risks associated with the Amish lifestyle. Specific educational opportunities are related to scalds, ignition of clothing, and ignition of highly flammable materials. A culturally sensitive burn prevention teaching tool, consisting of a magnetic storyboard, burn safety curriculum, and tests, was developed with the cooperation of one Old Order Amish community. The purpose of this study was to test the effectiveness of the tool in an Amish school. The teacher obtained parental permission and informed assent for the participation of the children. Pretesting was completed before the lessons began. The teacher told stories and arranged the magnets on the storyboard to show burn hazards involving lighters, stoves, kerosene heaters, gasoline-powered engines, and hot liquids used for canning, butchering, mopping, washing clothes, and making lye soap. The children were challenged to rearrange the pieces for a safer situation. Posttesting was performed 2 months after the pretest. Twenty-seven students (grades 1-8) participated. Tests were scored as a percentage of the 33 items answered correctly. The mean pretest score was 62 and the mean posttest score was 83. Statistical analysis using paired t-test demonstrated a highly significant improvement in test scores (P < .0001), with a power of more than 99%. This pilot study demonstrated that the burn prevention teaching tool was effective for improving knowledge in one classroom of Amish children. These results support expanded use and testing of this tool in other Amish schools. PMID- 22079909 TI - Comparison of reimbursements: thermal vs mechanical trauma. PMID- 22079910 TI - Management of severe rheumatological disease in the burn center. AB - In recent years, Burn Center has evolved to become a "wound intensive care unit" treating disease processes other than those due to thermal injury. Recent data have shown that more than 16% of admissions to Burn Centers are for nonburn injuries, particularly severe dermatologic diseases. The role of the Burn Center has been expanded to include treatment of patients with severe cutaneous manifestations of rheumatologic diseases. This approach has not been described before. All collagen vascular disease admissions to the Burn Center from 2005 to 2010 have been reviewed. There were 16 admissions where intensive wound management was a major component of the disease management. Disease processes included systemic lupus erythematosus, progressive systemic sclerosis, Raynaud's phenomenon, antiphospholipid syndrome, and dermatomyositis, among others. The authors describe five of these cases in detail. Comanagement of these patients by the Rheumatology and Burn services led to outstanding, successful outcomes. Collagen vascular diseases represent another area where the Burn Center may be the appropriate site for therapy. PMID- 22079911 TI - Risk factors for nosocomial infection and mortality in burn patients: 10 years of experience at a university hospital. AB - To evaluate the risk factors for nosocomial infection (NI) and mortality in a university hospital, 10-year data of burn patients were assessed retrospectively. The study was conducted at Erciyes University's Burn Center during 2000 and 2009. The records of 1190 patients were obtained. Overall, 131 (11%) patients had 206 NIs with an incidence density of 14.7 infections/1000 patient days. Burn wound infection (n = 109, 53%) was the most common NI. High (%TBSA burned) and late excision were found to be the most significant risk factors for the development of NI. Pseudomonas aeruginosa was the most frequent causative microorganism. However, the prevalence of multidrug-resistant Acinetobacter baumannii has increased in recent years with a prevalence of 47% in 2009. The carbapenem resistance of P. aeruginosa has decreased in recent years, whereas that of A. baumannii increased and it had a prevalence of 94% in the last year. Conversely, the most important risk factors for mortality were advanced age, high %TBSA and having an underlying disease. Prevention of NI is an important issue in burn units to reduce mortality rates. Early excision and wound closure are important therapeutic approaches for the prevention of burn wound infection. PMID- 22079912 TI - Application of split-thickness dermal grafts in deep partial- and full-thickness burns: a new source of auto-skin grafting. AB - Early tangential excision of nonviable burn tissue, followed by immediate skin grafting with autograft or allograft, has resulted in the improvement of burn patient survival. The aim of this study was to add split-thickness dermal grafts (STDGs) as a new source of auto-skin grafting tool to our reconstructive armamentarium in deep partial- and full-thickness burns and soft tissue defects. The authors successfully applied STDGs along with split-thickness skin grafts as a new source of auto-skin grafting in 11 deep partial- and full-thickness burns over a period of 1 year without any significant donor site morbidity. Dermal graft take was complete in all but one patient. There was no donor site healing problem, and donor site epithelization was completed generally 1 week later than split-thickness skin graft by semi-open technique. Autologous split-thickness skin grafting still remains the standard therapy for burn wound closure but may be in limited availability in severe burns. The authors conclude that STDGs may be a new source of auto-skin grafting tool in extensive deep partial- and full thickness burns. PMID- 22079913 TI - A novel technique for split-thickness skin donor site pain control: subcutaneous catheters for continuous local anesthetic infusion. PMID- 22079914 TI - Exploration of nonsurgical scar modification options: can the irregular surface of matured mesh graft scars be smoothed with microdermabrasion? AB - The purpose of this study was to determine, in principle, whether microdermabrasion can alter waffle-pattern (meshed split-thickness skin graft) burn scars after scar maturation. Matured waffle-pattern mesh-graft scars were treated with multiple microdermabrasion sessions over the course of a year (maximum 20). Before and after treatment, the treated scars and the control scar on the same patient were assessed with subjective and objective scar assessment tools (scar scales, cutometer [elasticity], laser Doppler flowmeter [vascularity], Semmes-Weinstein filaments [sensation], and high-resolution ultrasound [thickness]). The treatment resulted in continuous improvement of some physiologic skin functions like perfusion response (feedback), thickness, and elasticity when compared with nontreated scar, although no statistical significance was reached. Both Vancouver scar scale and patient assessment scales showed significant improvement. The study showed that even mature waffle pattern scars can be modified by minimally invasive interventions. Larger study groups and more economic treatment modalities need to be studied in the future. PMID- 22079915 TI - Herpes simplex activation prolongs recovery from severe burn injury and increases bacterial infection risk. AB - Recovery from severe burn injury is complicated by infections that are result of immune suppression created by massive inflammatory states. One indication of immune suppression may be activation of viruses like herpes simplex virus (HSV), which may negatively impact recovery. A 5-year retrospective review was performed of adult patients with >=30% TBSA burn injury. TBSA burn injury, length of hospital stay, ventilator days, mortality, and cultures were reviewed. Twenty-one patients had cutaneous HSV activation (HSV+) and 50 did not (HSV-). Age (44.2 vs 39.8 years) and TBSA burn injury (45.9 vs 45.5%) did not differ between the groups. Length of hospital stay (60.9 vs 39.8 days, P < .05) and ventilator days (34.9 vs 22.2 days, P < .05) were greater in HSV+ patients. HSV activation increased hospital stay (odds ratio [OR] 1.6, confidence interval [CI] 1.08-2.39, P < .05) and mechanical ventilation (OR 1.02, CI 1.00-1.05, P < .05). HSV activation increased the risk of developing positive Acinetobacter baumannii pulmonary cultures (OR 6.4, CI 1.8-22.3, P < .05) and methicillin-resistant Staphylococcus aureus wound cultures (OR 3.3, CI 1.2-9.6, P < .05). HSV activation also increased the risk of developing any positive A. baumannii cultures (OR 9.1, CI 1.9-44, P < .05). HSV activation during severe burn injury is associated with increased length of mechanical ventilation and hospital stay. In addition, these patients have an increased risk of infections from opportunistic bacteria. PMID- 22079916 TI - Reduced decorin, fibromodulin, and transforming growth factor-beta3 in deep dermis leads to hypertrophic scarring. AB - Hypertrophic scar (HTS) occurs after injuries involving the deep dermis, while superficial wounds (SWs) to the skin heal with minimal or no scarring. The levels of transforming growth factor (TGF)-beta1 and small leucine-rich proteoglycans (SLRPs) with fibroblast subtype and function may influence the development of HTS. The aim of this study was to characterize the expression and localization of factors that regulate wound healing including SLRPs, TGF-beta1, and TGF-beta3 in an experimental human SW and deep wound (DW) scar model including fibroblasts from superficial and deep layers of normal dermis. A 6-cm horizontal dermal scratch experimental wound was created, which consisted of progressively deeper wounds that were superficial at one end (0-0.75 mm deep) and deep (0.75-3 mm deep) at the other end, located on the anterior thigh of an adult male. Immunofluorescence staining, immunoblotting, reverse transcription polymerase chain reaction, and flow cytometry were performed to analyze the cellular and molecular differences between the SW scar and DW scar as well as fibroblasts isolated from superficial layer (L1) and deep layer (L5) of normal dermis. Comparing SWs and L1 fibroblasts, the expression of decorin, fibromodulin, and TGF-beta3 was considerably lower than in DWs and L5 fibroblasts; however, TGF beta1 was higher in the deeper dermal wounds. When compared with L1 fibroblasts, L5 fibroblasts had lower Thy-1 immunoreactivity and significantly higher expression of TGF-beta receptor type II. Decreased antifibrotic molecules in matrix of deep dermis of the skin and the unique features of the associated fibroblasts including an increased sensitivity to TGF-beta1 stimulation contribute to the development of HTS after injuries involving the deep dermis. PMID- 22079917 TI - Split skin graft application over an integrating, biodegradable temporizing polymer matrix: immediate and delayed. AB - The objective of this study is to further investigate the NovoSorbTM biodegradable polyurethane in generating dermal scaffolds; to perform a pilot study comparing the previously used spun mat against a recently developed NovoSorbTM foam, ascertaining the optimum structure of the matrix; and to evaluate the successful matrix as an immediate adjunct to split skin grafting and as a temporizing matrix in a prospective six-pig study. A pilot study comparing a previously investigated form of the polymer (spun mat) against a new structural form, a foam, was performed. This was followed by a six-pig study of the foam matrix with three treatment arms-autologous split skin graft alone, polymer foam with immediate engraftment, and polymer foam with delayed engraftment. The foams allowed less wound contraction than the spun mats. The foam structure is less dense (cheaper to produce and having less degradation products). The material remained in situ despite clinical wound infection. Proof of concept was achieved in both treatment modalities in the main study. Split skin graft applied immediately over the polymer foam was able to engraft successfully. The result was "thicker" to pinch and "flush" with the skin surrounding the wound. There was no significant difference in the degree of wound contraction between the graft alone and the polymer plus immediate graft groups. Split skin graft also "took" when applied to the surface of a polymer that had been applied to a wound 11 days earlier, again with a thicker result, flush with the surrounding skin. Split skin grafts alone left a persisting depression. However, a significant degree of wound contraction (compared with the other two groups) was observed in the polymer plus delayed graft group. This has prompted further investigation into "sealing" the polymer foam with a membrane, to prevent evaporative water loss, when the foam is to be used as a biodegradable temporizing matrix. The studies indicate that the NovoSorbTM platform will allow the creation of two inexpensive dermal matrix products; an immediate scaffold to allow a thicker grafting result and a biodegradable temporizing matrix (BTM) for wound integration after burn debridement while donor sites become reharvestable. However, further modification on the BTM structure is necessary to further reduce wound contraction pregrafting. PMID- 22079918 TI - Examination of local and systemic in vivo responses to electrical injury using an electrical burn delivery system. AB - Electrical injuries are devastating and are difficult to manage due to the complexity of the tissue damage and physiological impacts. A paucity of literature exists which describes models for electrical injury. To date, those models have been used primarily to demonstrate thermal and morphological effects at the points of contact. Creating a more representative model for human injury and further elucidating the physics and pathophysiology of this unique form of tissue injury could be helpful in designing stage-appropriate therapy and improving limb salvage. An electrical burn delivery system was developed to accurately and reliably deliver electrical current at varying exposure times. A series of Sprague-Dawley rats were anesthetized and subjected to injury with 1000 V of direct current at incremental exposure times (2-20 seconds). Whole blood and plasma were obtained immediately before shock, immediately postinjury, and then hourly for 3 hours. Laser Doppler images of tissue adjacent to the entrance and exit wounds were obtained at the outlined time points to provide information on tissue perfusion. The electrical exposure was nonlethal in all animals. The size and the depth of contact injury increased in proportion to the exposure times and were reproducible. Skin adjacent to injury (both entrance and exit sites) exhibited marked edema within 30 minutes. In adjacent skin of upper extremity wounds, mean perfusion units increased immediately postinjury and then gradually decreased in proportion to the severity of the injuries. In the lower extremity, this phenomenon was only observed for short contact times, while longer contact times had marked malperfusion throughout. In the plasma, interleukin-10 and vascular endothelial growth factor levels were found to be augmented by injury. Systemic transcriptome analysis revealed promising information about signal networks involved in dermatological, connective tissue, and neurological pathophysiological processes. A reliable and reproducible in vivo model has been developed for characterizing the pathophysiology of high-tension electrical injury. Changes in perfusion were observed near and between entrance and exit wounds that appear consistent with injury severity. Further studies are underway to correlate differential mRNA expression with injury severity. PMID- 22079919 TI - Efficacy and safety of procedural sedation and analgesia for burn wound care. AB - The study aim was to quantify efficacy and patient safety of registered nurse administered procedural sedation and analgesia in a regional burn center. The investigators conducted a review of procedural sedation forms for all pediatric and adult patients admitted to this burn center from January 1, 2005, through December 31, 2005, for demographic and clinical data including patient age, gender, body weight, TBSA, dates of burn injury and wound care procedures, length of procedure, pre- and postprocedural pain assessment, procedural sedation/analgesia medications and doses, adverse drug events, and related interventions. During the 12-month study period, a total of 328 burn patients received 1293 procedural sedation procedures; child subjects (<= 18 years) received 356 procedures and adult subjects (19-87 years) received 937 procedures. The mean (SD) length of the procedure was 60.1 (22.49) minutes with a range of 10 to 170 minutes. The mean subject age was 34.2 years (range: 6 weeks to 87 years), 67% were male, and the mean TBSA was 17% (0.5-68%). Ninety-four percent received fentanyl for analgesia and 85% received midazolam for anxiolysis and amnesia. The mean preprocedural pain score was 3.2 and the mean postprocedural pain score was 2 (t = 14.795; df = 1243; P < .001). Ten adverse events, all respiratory related, were documented in eight patients, two of whom experienced a second adverse event for an overall adverse event rate of 0.77%. No patient required intubation. Procedural sedation administered by a registered nurse competent in administration and monitoring in a burn center provided safe and effective pain management during wound care. PMID- 22079920 TI - Effectiveness of environmental-based educative program for disaster preparedness and burn management. AB - Preparedness is a necessity for proper handling of emergencies and disaster, particularly in Suez Canal and Sinai regions. To assure best success rates, educative programs should be environmentally based. Burn and fire preventive educative programs were tailored to adapt social and education levels of audience. In addition, common etiologies and applicability of preventive measures, according to local resources and logistics, were considered. Presentations were the main educative tool; they were made as simple as possible to assure best understanding. To assure continuous education, brochures and stickers, containing most popular mistakes and questions, were distributed after the sessions. Audience was classified according to their level of knowledge to health professional group; students groups; high-risk group; and lay people group. For course efficacy evaluation, pre- and posttests were used immediately before and after the sessions. Right answers in both tests were compared for statistical significance. Results showed significant acquisition of proper attitude and knowledge in all educated groups. The highest was among students and the least was in health professionals. Comprehensive simple environmental-based educative programs are ideal for rapid reform and community mobilization in our region. Activities should include direct contact, stickers and flyers, and audiovisual tools if possible. PMID- 22079921 TI - The potato chip really does look like Elvis! Neural hallmarks of conceptual processing associated with finding novel shapes subjectively meaningful. AB - Clouds and inkblots often compellingly resemble something else--faces, animals, or other identifiable objects. Here, we investigated illusions of meaning produced by novel visual shapes. Individuals found some shapes meaningful and others meaningless, with considerable variability among individuals in these subjective categorizations. Repetition for shapes endorsed as meaningful produced conceptual priming in a priming test along with concurrent activity reductions in cortical regions associated with conceptual processing of real objects. Subjectively meaningless shapes elicited robust activity in the same brain areas, but activity was not influenced by repetition. Thus, all shapes were conceptually evaluated, but stable conceptual representations supported neural priming for meaningful shapes only. During a recognition memory test, performance was associated with increased frontoparietal activity, regardless of meaningfulness. In contrast, neural conceptual priming effects for meaningful shapes occurred during both priming and recognition testing. These different patterns of brain activation as a function of stimulus repetition, type of memory test, and subjective meaningfulness underscore the distinctive neural bases of conceptual fluency versus episodic memory retrieval. Finding meaning in ambiguous stimuli appears to depend on conceptual evaluation and cortical processing events similar to those typically observed for known objects. To the brain, the vaguely Elvis like potato chip truly can provide a substitute for the King himself. PMID- 22079922 TI - Learning shapes spatiotemporal brain patterns for flexible categorical decisions. AB - Learning is thought to facilitate our ability to perform complex perceptual tasks and optimize brain circuits involved in decision making. However, little is known about the experience-dependent mechanisms in the human brain that support our ability to make fine categorical judgments. Previous work has focused on identifying spatial brain patterns (i.e., areas) that change with learning. Here, we take advantage of the complementary high spatial and temporal resolution of simultaneous electroencephalography-functional magnetic resonance imaging (EEG fMRI) to identify the spatiotemporal dynamics between cortical networks involved in flexible category learning. Observers were trained to use different decision criteria (i.e., category boundaries) when making fine categorical judgments on morphed stimuli (i.e., radial vs. concentric patterns). Our findings demonstrate that learning acts on a feedback-based circuit that supports fine categorical judgments. Experience-dependent changes in the behavioral decision criterion were associated with changes in later perceptual processes engaging higher occipitotemporal and frontoparietal circuits. In contrast, category learning did not modulate early processes in a medial frontotemporal network that are thought to support the coarse interpretation of visual scenes. These findings provide evidence that learning flexible criteria for fine categorical judgments acts on distinct spatiotemporal brain circuits and shapes the readout of sensory signals that provide evidence for categorical decisions. PMID- 22079923 TI - Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex. AB - Although sensory and motor systems support different functions, both systems exhibit experience-dependent cortical plasticity under similar conditions. If mechanisms regulating cortical plasticity are common to sensory and motor cortices, then methods generating plasticity in sensory cortex should be effective in motor cortex. Repeatedly pairing a tone with a brief period of vagus nerve stimulation (VNS) increases the proportion of primary auditory cortex responding to the paired tone (Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake J, Sudanagunta SP, Borland MS, Kilgard MP. 2011. Reversing pathological neural activity using targeted plasticity. Nature. 470:101-104). In this study, we predicted that repeatedly pairing VNS with a specific movement would result in an increased representation of that movement in primary motor cortex. To test this hypothesis, we paired VNS with movements of the distal or proximal forelimb in 2 groups of rats. After 5 days of VNS movement pairing, intracranial microstimulation was used to quantify the organization of primary motor cortex. Larger cortical areas were associated with movements paired with VNS. Rats receiving identical motor training without VNS pairing did not exhibit motor cortex map plasticity. These results suggest that pairing VNS with specific events may act as a general method for increasing cortical representations of those events. VNS movement pairing could provide a new approach for treating disorders associated with abnormal movement representations. PMID- 22079924 TI - Conscious access is linked to ongoing brain state: electrophysiological evidence from the attentional blink. AB - Neuroscience explanations of conscious access focus on neural events elicited by stimuli. In contrast, here, we used the attentional blink paradigm in combination with event-related brain potentials to examine whether the ongoing state of the brain before a stimulus can determine both conscious access and the poststimulus neural events associated with consciousness. Participants were required to detect 2 target letters from digit distractors while their brain activity was being recorded. Trials were classified based on whether the secondcritical target (T2) was detected. We found that T2-detection was predetermined by brain activity prior to the onset of the stimulation stream. Specifically, T2-detected trials were predicated by a frontocentral positive going deflection that started more than 200 ms before the stream began. Accurate T2 detection was also accompanied by enhanced poststimulus neural activity, as reflected by a larger P3b component. Furthermore, prestimulus and poststimulus markers of T2-detection were highly correlated with one another. We therefore argue that conscious experiences are shaped by potentially random fluctuations in neural activity. Overall, the results reveal that conscious access is underpinned by an important relationship involving predictive prestimulus neural activity and responsive poststimulus brain activity. PMID- 22079925 TI - Theta phase modulates multiple layer-specific oscillations in the CA1 region. AB - It was recently proposed that fast gamma oscillations (60-150 Hz) convey spatial information from the medial entorhinal cortex (EC) to the CA1 region of the hippocampus. However, here we describe 2 functionally distinct oscillations within this frequency range, both coupled to the theta rhythm during active exploration and rapid eye movement sleep: an oscillation with peak activity at ~80 Hz and a faster oscillation centered at ~140 Hz. The 2 oscillations are differentially modulated by the phase of theta depending on the CA1 layer; theta 80 Hz coupling is strongest at stratum lacunosum-moleculare, while theta-140 Hz coupling is strongest at stratum oriens-alveus. This laminar profile suggests that the ~80 Hz oscillation originates from EC inputs to deeper CA1 layers, while the ~140 Hz oscillation reflects CA1 activity in superficial layers. We further show that the ~140 Hz oscillation differs from sharp wave-associated ripple oscillations in several key characteristics. Our results demonstrate the existence of novel theta-associated high-frequency oscillations and suggest a redefinition of fast gamma oscillations. PMID- 22079926 TI - Abnormal changes of synaptic excitability in migraine with aura. AB - Migraine patients are characterized by altered cortical excitability and information processing between attacks. The relationship between these abnormalities is still poorly understood. In this study, visual evoked potentials (VEP) and proton magnetic resonance spectroscopy were recorded simultaneously in migraineurs and healthy subjects. In order to investigate the homeostatic-like plasticity in the visual cortex, cortical excitability was modified using transcranial direct current stimulation (tDCS). Before any stimulation, migraineurs showed significantly higher glutamate/creatine ratios (Glx/Cr) than healthy subjects. In healthy subjects, excitatory (anodal) tDCS caused an increase and inhibitory (cathodal) tDCS a decrease in the Glx/Cr ratio. Subsequent photic stimulation (PS) reversed the changes in Glx/Cr ratios, which returned back to baseline, demonstrating homeostatic-like metaplasticity in the control group. In migraine patients, both anodal and cathodal tDCS decreased the Glx/Cr ratio, which did not return to baseline after PS. While healthy subjects showed an increase in VEP amplitude under anodal and a reduction under cathodal tDCS, the modifiability of VEP under tDCS was reduced in migraineurs. The results demonstrate a reduced responsiveness of the occipital cortex to interventions that change cortical excitability in migraine. Moreover, altered glutamatergic neurotransmission seems to mediate the relation between abnormal cortical information processing and excitability in migraineurs. PMID- 22079927 TI - Corticosteroid induced decoupling of the amygdala in men. AB - The amygdala is a key regulator of vigilance and heightens attention toward threat. Its activity is boosted upon threat exposure and contributes to a neuroendocrine stress response via the hypothalamic-pituitary-adrenal (HPA) axis. Corticosteroids are known to control brain activity as well as HPA activity by providing negative feedback to the brain. However, it is unknown how corticosteroids affect the neural circuitry connected to the amygdala. Implementing a randomized, double-blind, placebo-controlled design, we here investigated the effects of 10-mg hydrocortisone on amygdala-centered functional connectivity patterns in men using resting state functional magnetic resonance imaging. Results showed generally decreased functional connectivity of the amygdala by corticosteroids. Hydrocortisone reduced "positive" functional coupling of the amygdala to brain regions involved in the initiation and maintenance of the stress response; the locus coeruleus, hypothalamus, and hippocampus. Furthermore, hydrocortisone reduced "negative" functional coupling of the amygdala to the middle frontal and temporal gyrus; brain regions known to be involved in executive control. A control analysis did not show significant corticosteroid modulation of visual cortex coupling, indicating that the amygdala decoupling was not reflecting a general reduction of network connectivity. These results suggest that corticosteroids may reduce amygdala's impact on brain processing in the aftermath of stress in men. PMID- 22079928 TI - Early distal axonopathy of the visual pathway in experimental diabetes. AB - Diabetic retinopathy is a leading cause of acquired blindness. Visual function disorders have been observed in diabetic patients with very early retinopathy or even before the onset of retinopathy. The aim of the present work was to analyze the visual pathway in an early stage of experimental diabetes. Diabetes was induced in Wistar rats by an i.p. injection of streptozotocin. A deficit in anterograde transport from the retina to the superior colliculus was observed 6 weeks after streptozotocin injection. At this time point, morphologic studies did not reveal retinal ganglion cell loss or substantial alterations in the superior colliculus. The optic nerve was morphometrically evaluated at intraorbital (unmyelinated and myelinated) and intracranial sections. In animals that had been diabetic for 6 weeks, a large increase in astrocyte reactivity occurred in the distal (but not the intraorbital) portion, which coincided with significant axon loss. Moreover, profound myelin alterations and altered morphologic features of oligodendrocyte lineage were observed at the distal (but not the proximal) optic nerve portion. The present results suggest that axoglial alterations at the distal portion of the optic nerve could be the first structural change in the diabetic visual pathway. PMID- 22079930 TI - Untapping mental health capital. PMID- 22079929 TI - Pivotal role of apoptosis signal-regulating kinase 1 in monoclonal free light chain-mediated apoptosis. AB - Renal failure, a major complication associated with multiple myeloma, is usually related to deposition of monoclonal immunoglobulin free light chains (FLCs) and directly contributes to morbidity and mortality in this disease. The present study focused on the cytotoxic effects of monoclonal FLCs. Human proximal tubular epithelial cells (HK-2) were examined after incubation with two human monoclonal FLCs (termed kappa2 and lambda3). Incubation of HK-2 cells for 24 and 48 hours with either FLCs at 1 mg/mL promoted activation of caspase-9 and caspase-3 and increased the rate of apoptosis. Because prior studies demonstrated that FLCs generated intracellular oxidative stress, our studies focused on the redox sensitive mitogen-activated protein kinase kinase kinase known as apoptosis signal-regulating kinase 1 (ASK1). A time-dependent increase in phosphorylation of ASK1 at T845, indicating activation of this enzyme, was observed. Small interfering RNA designed to reduce ASK1 expression in HK-2 cells successfully decreased ASK1, which was confirmed by Western blot analysis. Incubation of ASK1 depleted HK-2 cells with the two FLCs prevented the increase in apoptosis while pretreating HK-2 cell with nontargeting small interfering RNA did not prevent FLCs-mediated apoptosis. The combined data demonstrate that monoclonal FLCs activated the intrinsic apoptotic pathway in renal epithelial cells by activation of ASK1. PMID- 22079931 TI - Parenting for mental health: what does the evidence say we need to do? Report of Workpackage 2 of the DataPrev project. AB - The last decade has witnessed increasing interest in the promotion of mental health and well-being because of its importance for health and social functioning at individual level and for the social and economic well-being of societies. Recent research from a range of disciplines (including neurodevelopment, developmental psychology and genetics) has highlighted the importance of childhood, and particularly the first few years of life, for future mental, social and emotional development. The quality of the parent-child relationship and parenting more generally is one of the factors in determining outcomes. The objective of this review was to identify effective interventions to support parents, parenting and the parent-child relationship from the ante-natal period to adolescence. A systematic search of key electronic databases was undertaken to identify systematic reviews evaluating approaches to parenting support; 52 systematic reviews were identified. Results were synthesized qualitatively and reported under the following headings: (i) perinatal programmes; (ii) parenting support programmes in infancy and early years focused on enhancing caregiver sensitivity and attunement; (iii) formal parenting programmes focused on children's behaviour; (iv) parenting support for highest risk groups. The review provides a robust international evidence base of programmes which have been demonstrated to improve parenting and the mental health and well-being of children. Policies and programmes to support parenting offer much scope for improving mental health. Effective provision requires a skilled workforce and careful application of approaches that have been found to work. More research is needed to develop and identify interventions for some of the highest risk groups. PMID- 22079933 TI - Supporting decision-making processes for evidence-based mental health promotion. AB - The use of evidence is critical in guiding decision-making, but evidence from effect studies will be only one of a number of factors that will need to be taken into account in the decision-making processes. Equally important for policymakers will be the use of different types of evidence including implementation essentials and other decision-making principles such as social justice, political, ethical, equity issues, reflecting public attitudes and the level of resources available, rather than be based on health outcomes alone. This paper, aimed to support decision-makers, highlights the importance of commissioning high quality evaluations, the key aspects to assess levels of evidence, the importance of supporting evidence-based implementation and what to look out for before, during and after implementation of mental health promotion and mental disorder prevention programmes. PMID- 22079934 TI - Mental health and global well-being. AB - A range of evidence-based, cost-effective interventions can be implemented in parenting, at schools, at the workplace and in older age to promote mental health and well-being. Such programmes need to be supplemented with actions to build mental health capital and promote resilience to manage and cope with the global risks that face humankind over the coming years. Actions need to connect mental and physical health and individuals need to be connected through health-promoting social networks; living environments need to be designed to support mental health and well-being; well-being indicators that include material living conditions, quality of life and sustainability can help drive healthy public policy. There is an urgent need to invest in skills training in decision-making, social interactions, building trust and cooperative behaviour that support the family of humanity as a whole as it faces the unprecedented stressors resulting from climate change. PMID- 22079932 TI - Investing in mental health and well-being: findings from the DataPrev project. AB - A systematic review was conducted to determine the extent to which an economic case has been made in high-income countries for investment in interventions to promote mental health and well-being. We focused on areas of interest to the DataPrev project: early years and parenting interventions, actions set in schools and workplaces and measures targeted at older people. Economic evaluations had to have some focus on promotion of mental health and well-being and/or primary prevention of poor mental health through health-related means. Studies preventing exacerbations in existing mental health problems were excluded, with the exception of support for parents with mental health problems, which might indirectly affect the mental health of their children. Overall 47 studies were identified. There was considerable variability in their quality, with a variety of outcome measures and different perspectives: societal, public purse, employer or health system used, making policy comparisons difficult. Caution must therefore be exercised in interpreting results, but the case for investment in parenting and health visitor-related programmes appears most strong, especially when impacts beyond the health sector are taken into account. In the workplace an economic return on investment in a number of comprehensive workplace health promotion programmes and stress management projects (largely in the USA) was reported, while group-based exercise and psychosocial interventions are of potential benefit to older people. Many gaps remain; a key first step would be to make more use of the existence evidence base on effectiveness and model mid- to long-term costs and benefits of action in different contexts and settings. PMID- 22079935 TI - Mental health promotion and problem prevention in schools: what does the evidence say? AB - The European Union Dataprev project reviewed work on mental health in four areas, parenting, schools, the workplace and older people. The schools workpackage carried out a systematic review of reviews of work on mental health in schools from which it identified evidence-based interventions and programmes and extracted the general principles from evidence-based work. A systematic search of the literature uncovered 52 systematic reviews and meta-analyses of mental health in schools. The interventions identified by the reviews had a wide range of beneficial effects on children, families and communities and on a range of mental health, social, emotional and educational outcomes. The effect sizes associated with most interventions were generally small to moderate in statistical terms, but large in terms of real-world impacts. The effects associated with interventions were variable and their effectiveness could not always be relied on. The characteristics of more effective interventions included: teaching skills, focusing on positive mental health; balancing universal and targeted approaches; starting early with the youngest children and continuing with older ones; operating for a lengthy period of time and embedding work within a multi modal/whole-school approach which included such features as changes to the curriculum including teaching skills and linking with academic learning, improving school ethos, teacher education, liaison with parents, parenting education, community involvement and coordinated work with outside agencies. Interventions were only effective if they were completely and accurately implemented: this applied particularly to whole-school interventions which could be ineffective if not implemented with clarity, intensity and fidelity. The implications for policy and practice around mental health in schools are discussed, including the suggestion of some rebalancing of priorities and emphases. PMID- 22079936 TI - Reducing the silent burden of impaired mental health. AB - Mental and behavioural disorders account for about one-third of the world's disability due to all ill health amongst adults, with unipolar depressive disorders set to be the world's number one cause of ill health and premature death in 2030, affecting high- and low-income countries alike. There is a range of evidence-based cost-effective interventions that can be implemented in parenting, at schools, at the workplace and in older age that can promote health and well-being, reduce mental disorders, lead to improved productivity and increase resilience to cope with many of the stressors that are facing the world. These facts need to be better communicated to policy makers to ensure that the silent burden of impaired mental health is adequately heard and reduced. PMID- 22079937 TI - Psychosocial interventions in workplace mental health promotion: an overview. AB - A review based on the DataPrev final report concerning workplace mental health promotion is presented. Out of 4865 studies identified in a comprehensive bibliographical data search, 315 were selected for abstract screening and 79 were included in the final review. The studies were categorized in terms of their aims/expected outcomes and evaluated for quality on the grounds of their design and type of analysis. The most frequent aims were stress reduction and better coping, followed by increased job satisfaction and effectiveness, mental health enhancement and reduction in mental health-related absenteeism. In the 79 intervention studies, 99 outcome variables were measured using 163 instruments, mostly developed for the study purposes. Different intervention categories turned out to be used to attain the same aim, with skills training being the most popular (other approaches included improvement of occupational qualifications and working conditions, physical exercise, relaxation and multicomponent interventions). Among the few intervention programs that were implemented and evaluated in two or more studies, the Stress Inoculation Training (Cecil and Forman, in Effects of stress inoculation training and coworker support groups on teachers' stress. Journal of School Psychology, 28, 105, 1990) based on the model by Meichenbaum (Meichenbaum, in Stress Inoculation Training. Pergamon Press, New York, 1985) seemed to be the most promising. Its effectiveness, evidenced in a majority of the measures, was evaluated in studies using the randomized controlled design. This paper is illustrated by high-quality intervention studies. In high and moderate quality studies, positive effects were reported in about a half of the examined outcome variables. However, conclusive evidence of intervention programs effectiveness would require further research-repetition of studies using treatments equivalent to the experimental ones, and outcome evaluation taking into account other criteria, e.g. behavioural. PMID- 22079938 TI - Psychosocial interventions for the promotion of mental health and the prevention of depression among older adults. AB - The aim of this review was to assess the effectiveness of psychosocial interventions for the promotion of mental health and prevention of depression among older people. A systematic review of prospective controlled trials was conducted including 69 studies. The studies were divided into physical exercise, skill training, reminiscence, social activities, group support and multicomponent interventions. Data from 44 trials contributed to a meta-analysis of effectiveness. Overall, psychosocial interventions had a positive effect on quality of life and positive mental health. The pooled interventions also had a statistically significant effect on reduction in depressive symptoms. Social activities significantly improved positive mental health, life satisfaction and quality of life and reduced depressive symptoms. Based on the results of this study, duration of interventions is of importance, since interventions lasting for >3 months exhibited more positive effects compared with shorter interventions. Meaningful social activities, tailored to the older individual's abilities and preferences should be considered in aiming to improve mental health among older people. PMID- 22079939 TI - Long-term recovery of beta-cell function after partial pancreatectomy in humans. AB - Glucose homeostasis is significantly altered immediately after partial pancreatectomy. The present study examined the long-term consequences of a hemipancreatectomy in 10 patients with chronic pancreatitis and 10 patients with benign pancreatic and extrapancreatic tumors. A 240-minute oral glucose challenge was performed before and shortly after pancreatic surgery, as well as after a follow-up of 3.1 +/- 0.5 years. Plasma concentrations of glucose, insulin, and C peptide were determined; and indices of insulin sensitivity and insulin secretion were calculated. In both groups of patients, fasting and postchallenge glucose concentrations were significantly altered immediately after surgery, but returned to preoperative levels at the time of follow-up (P < .0001). Postchallenge insulin and C-peptide concentrations were reduced immediately after surgery (P < .0001), but were partly normalized at the time of follow-up (P < .0001). These changes were not accompanied by improvements in insulin sensitivity (Matsuda index). However, the oral disposition index revealed a significant recovery of beta-cell function at the time of follow-up (P < .05). These findings demonstrate a capacity for recovery of glucose control after partial pancreatectomy and suggest that beta-cell function can improve significantly over time even in adult humans. PMID- 22079940 TI - Applying narrow-band imaging in complement with white-light imaging cystoscopy in the detection of urothelial carcinoma of the bladder. AB - OBJECTIVES: To investigate the value of narrow-band imaging (NBI) flexible cystoscopy in the detection of urothelial carcinoma (UC) of the bladder. MATERIALS AND METHODS: Clinical data of 179 patients with suspected UC, who presented with gross hematuria, were collected at China PLA General Hospital from January 2009 to August 2010. These patients underwent white-light imaging (WLI) cystoscopy followed by NBI. The tumors were visualized, imaged, and recorded. Suspected UCs were biopsied or treated by transurethral resection, and then sent for pathologic examination. Detection results for NBI and WLI were compared. RESULTS: WLI and NBI confirmed UC in 143 patients; a total of 285 tumors were detected. The patient-level detection rates for NBI and WLI were 97.9% (140/143) and 88.8% (127/143), respectively (P = 0.002). The patient-level false-positive detection rates for NBI and WLI were 21.8% (39/179) and 29.1% (52/179), respectively (P = 0.12). NBI detected a total of 59 additional tumors (17.2%; 34pTa, 17pT1, 3pT2, and 5pTis) in 44 of 143 patients (30.8%). NBI found 1 additional tumor in 34 cases, 2 additional tumors in 6 cases, 3 additional tumors in 3 cases, and 4 additional tumors in 1 case. The mean +/- SD (range) number of identified UCs per patient was 1.97 +/- 0.67 (1-5) for NBI and 1.78 +/- 0.53 (1 4) for WLI (P = 0.01). The tumor-level detection rates for NBI and WLI were 96.8% and 79.3%, respectively (P < 0.001). CONCLUSIONS: Compared with WLI, NBI improves UC detection. It has a higher rate of detection and a comparative rate of false positive detection. NBI is simple and requires no dyeing. It can be conveniently applied to complement WLI. PMID- 22079942 TI - Regulation of task differentiation in wasp societies: a bottom-up model of the "common stomach". AB - Metapolybia wasps live in small societies (around one hundred adults) and rear their young in nests they construct on flat surfaces from plant materials. For processing nest paper, they must gather plant materials and process it into pulp with water. The water is collected by water foragers and is transferred to pulp foragers indirectly via a "common stomach." The common stomach, or social crop, is formed by generalist wasps called laborers. These wasps can engage in water exchange, store water in their crops, and may become specialist foragers or builders. We provide an alternative model for regulating task partitioning in construction behavior by using an agent based modeling framework parameterized by our field observations. Our model predicts that assessing colony needs via individual interactions with the common stomach leads to a robust regulation of task partitioning in construction behavior. By using perturbation experiments in our simulations, we show that this emergent task allocation is able to dynamically adapt to perturbations of the environment and to changes in colony level demands or population structure. The robustness of our model stems from the fact that the common stomach is both a strong buffer and a source of several feedback mechanisms that affect the individual wasps. We show that both the efficiency and the task fidelity of these colonies are dependent upon colony size. We also demonstrate that the emergence of specialist wasps (individuals with high task fidelity) does not require any special initial conditions or reinforcement at the individual level, but it is rather a consequence of colony level workflow stability. Our model closely mimics the behavior of Metapolybia wasps, demonstrating that a regulation mechanism based on simple pair-wise interactions through a common stomach is a plausible hypothesis for the organization of collective behavior. PMID- 22079941 TI - Maternal gametic transmission of translocations or inversions of human chromosome 11p15.5 results in regional DNA hypermethylation and downregulation of CDKN1C expression. AB - Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with genetic or epigenetic alterations in one of two imprinted domains on chromosome 11p15.5. Rarely, chromosomal translocations or inversions of chromosome 11p15.5 are associated with BWS but the molecular pathophysiology in such cases is not understood. In our series of 3 translocation and 2 inversion patients with BWS, the chromosome 11p15.5 breakpoints map within the centromeric imprinted domain, 2. We hypothesized that either microdeletions/microduplications adjacent to the breakpoints could disrupt genomic sequences important for imprinted gene regulation. An alternate hypothesis was that epigenetic alterations of as yet unknown regulatory DNA sequences, result in the BWS phenotype. A high resolution Nimblegen custom microarray was designed representing all non-repetitive sequences in the telomeric 33 Mb of the short arm of human chromosome 11. For the BWS-associated chromosome 11p15.5 translocations and inversions, we found no evidence of microdeletions/microduplications. DNA methylation was also tested on this microarray using the HpaII tiny fragment enrichment by ligation-mediated PCR (HELP) assay. This high-resolution DNA methylation microarray analysis revealed a gain of DNA methylation in the translocation/inversion patients affecting the p ter segment of chromosome 11p15, including both imprinted domains. BWS patients that inherited a maternal translocation or inversion also demonstrated reduced expression of the growth suppressing imprinted gene, CDKN1C in Domain 2. In summary, our data demonstrate that translocations and inversions involving imprinted domain 2 on chromosome 11p15.5, alter regional DNA methylation patterns and imprinted gene expression in cis, suggesting that these epigenetic alterations are generated by an alteration in "chromatin context". PMID- 22079943 TI - Campus quarantine (Fengxiao) for curbing emergent infectious diseases: lessons from mitigating A/H1N1 in Xi'an, China. AB - During the 2009 A/H1N1 influenza pandemic, very strict interventions including campus quarantine (Fengxiao) (restrictions on the movements of university personnel) were taken in mainland China to slow down the initial spread of the disease from the university network to a wider community. The decision for implementation and/or relaxation of Fengxiao depends on the assessment of the level of infection within the university network compared with that in the wider community and on the degree of interruption of normal academic activities and the associated social/economic costs. However, the most important consideration influencing the decision is whether the initiation and termination of Fengxiao can alter the pattern of disease spread in the entire community for effective prevention and control of the emerging disease. Here we formulate and analyze a dynamic model to evaluate the effectiveness of Fengxiao as a social distance measure for curbing the outbreak in major cities of China. Using data from the initial laboratory-confirmed cases admitted to the 8th Hospital of Xi'an (the capital city of the Shaanxi Province), we estimated the reproduction number for the period under consideration in the range 1.273-1.784 and concluded that the population's mobility, combined with the suspension of the Fengxiao strategy, was a key factor contributing to a subsequent epidemic wave. Fengxiao in China is a reversal of the usual strategy of school closures adopted in many other countries, but the lessons learnt from it may be useful for disease management in other countries where restrictions on the movements across a facility boundary and close monitoring of the infection within the facility are feasible in the long term. PMID- 22079945 TI - ERP investigation of study-test background mismatch during face recognition in schizophrenia. AB - Old/new effects on event-related potentials (ERP) were explored in 20 patients with schizophrenia and 20 paired comparison subjects during unfamiliar face recognition. Extrinsic perceptual changes - which influence the overall familiarity of an item while retaining face-intrinsic features for use in structural face encoding - were manipulated between the study phase and the test. The question raised here concerns whether these perceptual incongruities would have a different effect on the sense of familiarity and the corresponding behavioral and ERP measures in the two groups. The results showed that schizophrenia patients were more inclined to consider old faces shown against a new background as distractors. This drop in face familiarity was accompanied by the disappearance of ERP old/new effects in this condition, i.e., FN400 and parietal old/new effects. Indeed, while ERP old/new recognition effects were found in both groups when the picture of the face was physically identical to the one presented for study, the ERP correlates of recognition disappeared among patients when the background behind the face was different. This difficulty in disregarding a background change suggests that recognition among patients with schizophrenia is based on a global perceptual matching strategy rather than on the extraction of configural information from the face. The correlations observed between FN400 amplitude, the rejection of faces with a different background, and the reality-distortion scores support the idea that the recognition deficit found in schizophrenia results from early anomalies that are carried over onto the parietal ERP old/new effect. Face-extrinsic perceptual variations provide an opportune situation for gaining insight into the social difficulties that patients encounter throughout their lives. PMID- 22079944 TI - Control of working memory content in schizophrenia. AB - People with schizophrenia (PSZ) exhibit signs of reduced working memory (WM) capacity. However, this may reflect an impairment in managing its content, e.g. preventing irrelevant information from taking up available storage space, rather than a true capacity reduction. We tested the ability to eliminate and update WM content in 38 PSZ and 30 healthy control subjects (HCS). Images of real-world objects were presented consecutively, and a tone cued the item most likely to be tested for memory. On half the trials, randomly intermixed, a second tone occurred. Participants were informed that the item cued by the second tone was now the most likely to be tested, and the item cued by the first tone now the least likely, providing incentive to eliminate the first cued item from WM. Both HCS and PSZ displayed a robust performance advantage for cued items. Unexpectedly, PSZ more efficiently removed the no-longer-essential item from WM than HCS. The magnitude of the WM clearance of this first cued item correlated with memory performance for the newly prioritized second cued item in PSZ, indicating that it was adaptive. However, WM clearance was not associated with WM capacity, ruling out the need to budget limited resources as an explanation for greater clearance in PSZ. A robust correlation between WM clearance and poverty of speech in PSZ instead suggests that the propensity to rapidly clear non essential information and minimize the number of items in WM may be the reflection of a negative symptom trait. This finding may reflect a more general tendency of PSZ to focus processing more narrowly than HCS. PMID- 22079946 TI - Neuronal deficit in medial pulvinar from right but not left hemisphere in schizophrenia. PMID- 22079947 TI - Body temperature regulation and outcome after cardiac arrest and therapeutic hypothermia. AB - OBJECTIVE: Therapeutic temperature modulation is recommended after cardiac arrest (CA). However, body temperature (BT) regulation has not been extensively studied in this setting. We investigated BT variation in CA patients treated with therapeutic hypothermia (TH) and analyzed its impact on outcome. METHODS: A prospective cohort of comatose CA patients treated with TH (32-34 degrees C, 24h) at the medical/surgical intensive care unit of the Lausanne University Hospital was studied. Spontaneous BT was recorded on hospital admission. The following variables were measured during and after TH: time to target temperature (TTT=time from hospital admission to induced BT target <34 degrees C), cooling rate (spontaneous BT-induced BT target/TTT) and time of passive rewarming to normothermia. Associations of spontaneous and induced BT with in-hospital mortality were examined. RESULTS: A total of 177 patients (median age 61 years; median time to ROSC 25 min) were studied. Non-survivors (N=90, 51%) had lower spontaneous admission BT than survivors (median 34.5 [interquartile range 33.7 35.9] degrees C vs. 35.1 [34.4-35.8] degrees C, p=0.04). Accordingly, time to target temperature was shorter among non-survivors (200 [25-363]min vs. 270 [158 375]min, p=0.03); however, when adjusting for admission BT, cooling rates were comparable between the two outcome groups (0.4 [0.2-0.5] degrees C/h vs. 0.3 [0.2 0.4] degrees C/h, p=0.65). Longer duration of passive rewarming (600 [464-744]min vs. 479 [360-600]min, p<0.001) was associated with mortality. CONCLUSIONS: Lower spontaneous admission BT and longer time of passive rewarming were associated with in-hospital mortality after CA and TH. Impaired thermoregulation may be an important physiologic determinant of post-resuscitation disease and CA prognosis. When assessing the benefit of early cooling on outcome, future trials should adjust for patient admission temperature and use the cooling rate rather than the time to target temperature. PMID- 22079948 TI - Total epinephrine dose during asystole and pulseless electrical activity cardiac arrests is associated with unfavourable functional outcome and increased in hospital mortality. AB - AIM: Epinephrine is the drug of choice during advanced cardiac life support. The cumulative dose of epinephrine applied during resuscitation was shown to be independently associated with unfavourable outcome after ventricular fibrillation cardiac arrest in humans. Our objective was to investigate the association between the cumulative dose of epinephrine applied during resuscitation and unfavourable functional outcome and in-hospital mortality, in patients with asystole and pulseless electric activity. METHODS: Data on 946 patients admitted to the emergency department after resuscitation of witnessed in-hospital and out of hospital cardiac arrest with asystole or pulseless electric activity were retrieved from the cardiac arrest registry of the emergency department at the Vienna General Hospital/Medical University of Vienna. Data were documented according to Utstein Style. The risk factor was cumulative epinephrine categorized into quartiles. The endpoints were unfavourable functional outcome and in-hospital mortality. RESULTS: The median cumulative amount of epinephrine administered was 2mg (IQR 0-5), ranging from 1 to 50mg. Of all patients 643/946 (68%) had an unfavourable functional outcome, 649/946 (69%) died during hospital stay. The multivariable analysis showed a statistically significant increasing risk for unfavourable functional outcome and in-hospital mortality outcome with increasing cumulative doses of epinephrine (unfavourable functional outcome: OR 1 1.45-2.25-2.95 over quartiles of epinephrine; in hospital mortality: OR 1-1.35 2.15-2.82 over quartiles of epinephrine). CONCLUSION: Our results show that an increasing cumulative dose of epinephrine during resuscitation of patients with asystole and pulseless electric activity is an independent risk factor for unfavourable functional outcome and in-hospital mortality. PMID- 22079949 TI - A new liposome-based gene delivery system targeting lung epithelial cells using endothelin antagonist. AB - We formulated a new gene delivery system based on targeted liposomes. The efficacy of the delivery system was demonstrated in in vitro and in vivo models. The targeting moiety consists of a high-affinity 7-amino-acid peptide, covalently and evenly conjugated to the liposome surface. The targeting peptide acts as an endothelin antagonist, and accelerates liposome binding and internalization. It is devoid of other biological activity. Liposomes with high phosphatidyl serine (PS) were specially formulated to help their fusion with the endosomal membrane at low pH and enable release of the liposome payload into the cytoplasm. A DNA payload, pre-compressed by protamine, was encapsulated into the liposomes, which directed the plasmid into the cell's nucleus. Upon exposure to epithelial cells, binding of the liposomes occurred within 5-10 min, followed by facilitated internalization of the complex. Endosomal escape was complete within 30 min, followed by DNA accumulation in the nucleus 2h post-transfection. A549 lung epithelial cells transfected with plasmid encoding for GFP encapsulated in targeted liposomes expressed significantly more protein than those transfected with plasmid complexed with Lipofectamine. The intra-tracheal instillation of plasmid encoding for GFP encapsulated in targeted liposomes into rat lungs resulted in the expression of GFP in bronchioles and alveoli within 5 days. These results suggest that this delivery system has great potential in targeting genes to lungs. PMID- 22079950 TI - Expression of Wnt9, TCTP, and Bmp1/Tll in sea cucumber visceral regeneration. AB - We employ non-radioactive in situ hybridization techniques, which combine good tissue morphology preservation with high sensitivity of transcript detection, to map gene expression in the regenerating digestive tube of the sea cucumber Holothuriaglaberrima. We investigated localization of transcripts of Wnt9, TCTP, and Bmp1/Tll, the genes that have been previously known to be implicated in embryogenesis and cancer. The choice was determined by our long-term goal of trying to understand how the developmental regulatory pathways known to be involved in tumor development can be activated in post-traumatic regeneration without leading to malignant growth. The gene expression data combined with the available morphological information highlight the gut mesothelium (the outer layer of the digestive tube) as a highly dynamic tissue, whose cells undergo remarkable changes in their phenotype and gene expression in response to injury. This reversible transition of the gut mesothelium from a complex specialized tissue to a simple epithelium composed of rapidly proliferating multipotent cells seems to depend on the expression of genes from multiple developmental/cancer related pathways. PMID- 22079951 TI - Use of propofol in pediatric intensive care units: a national survey in Germany. AB - OBJECTIVE: Propofol is not licensed for sedation in pediatric intensive care medicine mainly due to the risk of propofol infusion syndrome. Nevertheless, it is applied by many pediatric intensive care units. The aim of this national survey was to asses the current use of propofol in pediatric intensive care units in Germany. DESIGN: We performed a nationwide survey. The questionnaire assessed the intensive care unit type, patient numbers, dosing, duration, age and time limits, indications, side effects, and institutional protocols for propofol usage. SETTING: Pediatric intensive care units in Germany. SUBJECTS: Questionnaire about routine use of propofol sent to 214 pediatric departments. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred ninety-four questionnaires (90.7%) were returned, ten had to be censored. The final analysis comprised 184 questionnaires (134 pediatric/neonatal intensive care units, 28 pediatric intensive care units, 22 neonatal intensive care units). Seventy-nine percent of intensive care units (n = 145 of 184) used propofol in children under the age of 16 yrs. Of these, 98% were for bolus application (n = 142 of 145), 78% for infusion >=3 hrs (n = 113 of 145), and 33% for infusion >3 hrs (n = 48 of 145). A lower age limit was applied by 52% (n = 75 of 145) and a dose limit by 51% (n = 74 of 145). The median dose limit was 4 mg/kg/hr; 48% (n = 70 of 145) used 3 mg/kg/hr or less. A time limit was applied by 98% (n = 46 of 47), 70% (n = 33 of 47) used it for <=24 hrs, and 30% (n = 15 of 47) for >24 hrs. MAIN INDICATIONS FOR PROPOFOL APPLICATION WERE: difficult sedation (44%), postoperative ventilation (43%), and difficult extubation (30%). Seven cases of propofol infusion syndrome were reported by seven centers. CONCLUSIONS: This study shows that propofol is used off-license by many pediatric intensive care units in Ge. The majority of users has adopted tightly controlled regimens for propofol sedation, and limits the dose to <=3-4 mg/kg/hr and the maximum application time to 24-48 hrs. PMID- 22079952 TI - The role of fecal calprotectin and lactoferrin in the diagnosis of necrotizing enterocolitis. AB - BACKGROUND: Early detection of necrotizing enterocolitis can improve the prognosis, however, there is not a reliable laboratory test to detect either newborns at risk for necrotizing enterocolitis development or those at early stages of the disease. Since fecal lactoferrin and fecal calprotectin are inflammatory markers of gastrointestinal diseases, it was hypothesized that both these biomarkers could be successfully used in the diagnosis of necrotizing enterocolitis. METHODS: In a prospective study, fecal lactoferrin and fecal calprotectin concentrations of 14 newborns with necrotizing enterocolitis and consecutively admitted 40 healthy preterm, and 23 healthy full-term newborns were measured with enzyme-linked immunosorbent assay technique. RESULTS: Mean fecal lactoferrin and fecal calprotectin were not different between preterm and full term newborns (p = .235 and p = .845, respectively), or those who were diagnosed with necrotizing enterocolitis or not (p = .545 and p = .968, respectively). Prevalence of necrotizing enterocolitis was 1.51% (14 of 2734). Stage of the disease did not have a statistical effect on mean levels (p = .694 and p = .267, respectively). Mean fecal lactoferrin and fecal calprotectin levels were not different in the case of breastfeeding (p = .623 and p = .792, respectively). CONCLUSION: Neither fecal lactoferrin nor fecal calprotectin has a role in the identification of necrotizing enterocolitis, especially in early stages of the disease. Further studies on wider necrotizing enterocolitis series are needed for a more definite conclusion. PMID- 22079953 TI - Evaluation and comparison of parental needs, stressors, and coping strategies in a pediatric intensive care unit. AB - OBJECTIVE: To evaluate and compare the needs, stressors, and coping strategies of mothers and fathers in a pediatric intensive care unit, and to advance the development of the COMPASS questionnaire for examining parent experiences. DESIGN: Prospective cohort study using a modified version of a pilot questionnaire, incorporating a series of 58 questions based on a visual analog scale in three categories of needs, stressors, and coping strategies. SETTING: Tertiary pediatric intensive care unit, Southampton University Hospitals, Southampton, UK. SUBJECTS: A total of 182 parents (91 mothers and 91 fathers) of children admitted to the pediatric intensive care unit. INTERVENTIONS: Collection and analysis of needs, stressors, and coping strategies scores. MEASUREMENTS AND MAIN RESULTS: Both parents identified the need for honest, open, timely, and understandable information, with access to their child as paramount. Parents found feelings of uncertainty and helplessness to be particularly stressful. The main coping strategies employed by parents were related to trust, assurance, and believing in positive outcomes. The particular needs and stressors of mothers and fathers were found to be similar. There were, however, some statistically significant differences in stressors: mothers had higher stress scores regarding how their child looked, not being able to care for them, witnessing procedures, and on leaving their child as compared with fathers. There were no statistically significant differences in coping mechanisms between the sexes. CONCLUSIONS: Acute parental experiences can be documented using the COMPASS questionnaire. This study highlights the principal needs, stressors, and coping strategies of parents of children in the pediatric intensive care unit. The experiences of mothers and fathers are similar, but we identify some differences in stressors between the sexes. PMID- 22079955 TI - Comparative effects of bronchoalveolar lavage with saline, surfactant, or perfluorocarbon in experimental meconium aspiration syndrome. AB - OBJECTIVE: Today, in meconium aspiration syndrome, treatment focuses on bronchoalveolar lavage, because it removes meconium and proinflammatory factors from airways. This technique might be more effective if different solutions were used such as saline solution, a protein-free surfactant, or a perfluorocarbon, because these would be less inhibited by meconium proteins. SETTING: Pulmonary physiology research unit, Cruces Hospital. DESIGN: Prospective, randomized study. SUBJECTS: We studied 24 lambs (<6 days) on mechanical ventilation for 180 mins. Catheters were placed and femoral and pulmonary arteries pressures registered (systemic and pulmonary arterial pressures). INTERVENTIONS: Lambs were instilled with 20% meconium (3-5 mL/Kg) and were randomly assigned to one of the following groups (n = 6): control: only continuous mechanical ventilation; saline bronchoalveolar lavage: bronchoalveolar lavage with 30 mL/kg of saline solution; dilute surfactant bronchoalveolar lavage: bronchoalveolar lavage with 32 mL/kg of diluted surfactant (lucinactant, 10 mg/mL); or perfluorocarbon bronchoalveolar lavage: bronchoalveolar lavage with 30 mL/kg of perfluorocarbon. MEASUREMENTS AND MAIN RESULTS: Blood gases, cardiovascular parameters, and pulmonary mechanics were assessed. Meconium instillation produced severe hypoxia, hypercapnia, acidosis, and pulmonary hypertension with impairment of pulmonary mechanics (p < .05). Lung lavage with dilute surfactant resulted in the resolution of pulmonary hypertension as well as better gas exchange and pulmonary mechanics than the control group (p < .05). Bronchoalveolar lavage with perfluorocarbon produced a transient improvement in gas exchange and ventilatory indices in comparison with control and saline bronchoalveolar lavage groups. CONCLUSIONS: In lambs with meconium aspiration syndrome, bronchoalveolar lavage with diluted lucinactant is an effective therapy producing significant improvements in gas exchange, pulmonary hypertension, and pulmonary mechanics. In addition, bronchoalveolar lavage with perfluorocarbon appears to confer some advantages over lavage with equal volumes of saline or no lavage. PMID- 22079956 TI - Personnel and unit factors impacting outcome after cardiac arrest in a dedicated pediatric cardiac intensive care unit. AB - OBJECTIVE: To assess the impact of personnel and unit factors on outcome from cardiac arrest in a dedicated pediatric cardiac intensive care unit. DESIGN: Retrospective medical record review. SETTING: Dedicated cardiac intensive care unit at a quaternary academic children's hospital. PATIENTS: Children and young adults who had cardiac arrest while cared for in the pediatric cardiac intensive care unit from January 1, 2006, to December 31, 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred two index cardiac arrests over a 3-yr period in our pediatric cardiac intensive care unit were reviewed. We defined successful resuscitation as either return of spontaneous circulation or successful cannulation to extracorporeal membrane oxygenation. Differences in resuscitation rates were assessed across categorical systems variables using logistic regression. The rate of successful resuscitation was 84% (return of spontaneous circulation 74%, extracorporeal membrane oxygenation 10%). Survival to hospital discharge was 48% for patients who had a cardiac arrest. 11% of arrests during the week and 31% during weekends (odds ratio 3.8; 95% confidence interval 1.2-11.5) were not successfully resuscitated. Unsuccessful resuscitation was significantly more likely when the primary nurse had <1 yr of experience in the pediatric cardiac intensive care unit (50% <1 yr vs. 13% >1 yr; odds ratio 6.8; confidence interval 1.5-31.0). Cardiac arrest on a weekend day and <1-yr pediatric cardiac intensive care unit nursing experience were also associated with unsuccessful resuscitation in a multivariable model. Resuscitation outcomes were similar when senior intensive care unit attending physicians were on-call at the time of arrest compared with other intensive care unit staff (17% unsuccessful vs. 15%; odds ratio 1.2; confidence interval 0.4-3.7). Arrests where the attending physician was present at the onset resulted in unsuccessful resuscitation 18% of the time vs. 14% for events where the attending was not present (odds ratio 1.3; confidence interval 0.5-3.9). CONCLUSIONS: Our data suggest that personnel and unit factors may impact outcome after cardiac arrest in a pediatric cardiac intensive care unit. Weekend arrests and less experience of the primary nurse were risk factors for unsuccessful resuscitation. Neither presence at arrest onset nor experience of the attending cardiac intensivist was associated with outcome. PMID- 22079957 TI - Neurally triggered breaths have reduced response time, work of breathing, and asynchrony compared with pneumatically triggered breaths in a recovering animal model of lung injury. AB - OBJECTIVE: Our objective was to compare response time, pressure time product as a reflection of work of breathing, and incidence and type of asynchrony in neurally vs. pneumatically triggered breaths in a spontaneously breathing animal model with resolving lung injury. DESIGN: Prospective animal study. SETTING: Experimental laboratory. SUBJECTS: Male Yorkshire pigs. INTERVENTIONS: Intubated, sedated pigs were ventilated using neurally adjusted ventilatory assist and pressure support ventilation with healthy and sick/recruited lungs. After injury, the lung was recruited using a computer-driven protocol. Respiratory mechanics were determined using a forced oscillation technique, and airway flow and pressure waveforms were acquired using a pneumotachograph. MEASUREMENTS AND MAIN RESULTS: Waveforms were analyzed for trigger delay, pressure time product, and asynchrony. Trigger delay was defined as the time interval (ms) from initiation of a breath to the beginning of ventilator pressurization. Pressure time product was measured as the area of the pressure curve for animal effort (area A) and ventilator response (area B). Asynchrony was classified according to triggering problems, adequacy of flow delivery, and adequate breath termination. Mean values were compared using the Wilcoxon signed-ranks test (p < .05). Trigger delay (ms) was less in neurally triggered breaths (pressure support ventilation healthy 104 +/- 27 vs. neurally adjusted ventilatory assist healthy 72 +/- 30, pressure support ventilation sick/recruited 77 +/- 18 vs. neurally adjusted ventilatory assist sick/recruited 38 +/- 18, p < .01). Pressure time product areas A and B were decreased for neurally triggered breaths compared with pressure support ventilation in both healthy and recruited animals (p <= .02). Overall, the percentage of asynchrony was less for neurally adjusted ventilatory assist breaths in the recruited animals (pressure support ventilation 27% and neurally adjusted ventilatory assist 6%). CONCLUSIONS: Neurally triggered breaths have reduced asynchrony, trigger delay, and pressure time product, which may indicate reduced work of breathing associated with less effort to trigger the ventilator and faster response to effort. Further study is required to demonstrate if these differences will lead to decreased days of ventilation and less use of sedation in patients. PMID- 22079954 TI - The randomized comparative pediatric critical illness stress-induced immune suppression (CRISIS) prevention trial. AB - OBJECTIVES: Nosocomial infection/sepsis occurs in up to 40% of children requiring long-term intensive care. Zinc, selenium, glutamine, metoclopramide (a prolactin secretalogue), and/or whey protein supplementation have been effective in reducing infection and sepsis in other populations. We evaluated whether daily nutriceutical supplementation with zinc, selenium, glutamine, and metoclopramide, compared to whey protein, would reduce the occurrence of nosocomial infection/sepsis in this at-risk population. DESIGN: Randomized, double-blinded, comparative effectiveness trial. SETTING: Eight pediatric intensive care units in the National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PATIENTS: Two hundred ninety-three long term intensive care patients (age 1-17 yrs) expected to require >72 hrs of invasive care. INTERVENTIONS: Patients were stratified according to immunocompromised status and center and then were randomly assigned to receive daily enteral zinc, selenium, glutamine, and intravenous metoclopramide (n = 149), or daily enteral whey protein (n = 144) and intravenous saline for up to 28 days of intensive care unit stay. The primary end point was time to development of nosocomial sepsis/infection. The analysis was intention to treat. MEASUREMENTS AND MAIN RESULTS: There were no differences by assigned treatment in the overall population with respect to time until the first episode of nosocomial infection/sepsis (median whey protein 13.2 days vs. zinc, selenium, glutamine, and intravenous metoclopramide 12.1 days; p = .29 by log-rank test) or the rate of nosocomial infection/sepsis (4.83/100 days whey protein vs. 4.99/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .81). Only 9% of the 293 subjects were immunocompromised and there was a reduction in rate of nosocomial infection/sepsis with zinc, selenium, glutamine, and intravenous metoclopramide in this immunocompromised group (6.09/100 days whey protein vs. 1.57/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .011). CONCLUSION: Compared with whey protein supplementation, zinc, selenium, glutamine, and intravenous metoclopramide conferred no advantage in the immune competent population. Further evaluation of zinc, selenium, glutamine, and intravenous metoclopramide supplementation is warranted in the immunocompromised long-term pediatric intensive care unit patient. PMID- 22079959 TI - A feasibility study on gamma-ray tomography by Monte Carlo simulation for development of portable tomographic system. AB - The electron beam X-ray tomographic scanner has been used in industrial and medical field since it was developed two decades ago. However, X-ray electron beam tomography has remained as indoor equipment because of its bulky hardware of X-ray generation devices. By replacing X-ray devices of electron beam CT with a gamma-ray source, a tomographic system can be a portable device. This paper introduces analysis and simulation results on industrial gamma-ray tomographic system with scanning geometry similar to electron beam CT. The gamma-ray tomographic system is introduced through the geometrical layout and analysis on non-uniformly distributed problem. The proposed system adopts clamp-on type device to actualize portable industrial system. MCNPx is used to generate virtual experimental data. Pulse height spectra from F8 tally of MCNPx are obtained for single channel counting data of photo-peak and gross counting. Photo-peak and gross counting data are reconstructed for the cross-sectional image of simulation phantoms by ART, Total Variation algorithm and ML-EM. Image reconstruction results from Monte Carlo simulation show that the proposed tomographic system can provide the image solution for industrial objects. Those results provide the preliminary data for the tomographic scanner, which will be developed in future work. PMID- 22079958 TI - Structural insight into the role of the human melanocortin 3 receptor cysteine residues on receptor function. AB - Melanocortin-3 receptor (MC3R), expressed in the hypothalamus and limbic systems of the brain, as well as by peripheral sites, plays an important role in the regulation of energy homeostasis and other physiological functions. Past work shows that MC3R-deficiency resulted in fat mass increase, feeding efficiency increase, hyperleptinemia and mild hyperinsulinemia in mice and human. MC3R belongs to G-protein coupled receptor (GPCR) family and many studies indicate that some cysteine residues in GPCR play key roles in maintaining receptor tertiary structure and function. In this study, we examined the role of cysteine residues in MC3R on receptor function. Human MC3R (hMC3R) has eighteen cysteine residues where they are located in the extracellular loops (ELs), the transmembrane domains (TMs) and the intracellular loops (ILs). We replaced these cysteines with serine and expressed these receptors in HEK-293 cells which lack endogenous MC3R. Our results indicate that five cysteines in eighteen of the hMC3R are important for hMC3R function. Mutations, C305S, C311S, and C313S in EL3, resulted in significant decrease in receptor expression and receptor function while two other mutations C115S and C162S in TM3 significantly decreased NDP-MSH binding affinity and potency. These results suggest that extracellular cysteine residue 305, 311 and 313 are crucial for receptor expression and the transmembrane cysteine residue, C115 and 162 are important for ligand binding and signaling. These findings provide important insights into the importance of cysteine residues of hMC3R on receptor tertiary structure and function. PMID- 22079960 TI - Determination of 241Pu in nuclear waste slurries: a comparative study using LSC and ICP-MS. AB - (241)Pu was determined in slurry samples from a nuclear reactor decommissioning project at the Paul Scherrer Institute (Switzerland). To validate the results, the (241)Pu activities of five samples were determined by LSC (TriCarb and Quantulus) and ICP-MS, with each instrument at a different laboratory. In lack of certified reference materials for (241)Pu, the methods were further validated using the (241)Pu information values of two reference sediments (IAEA-300 and IAEA-384). Excellent agreement with the results was found between LSC and ICP-MS in the nuclear waste slurries and the reference sediments. PMID- 22079961 TI - Subthreshold diode laser micropulse photocoagulation versus intravitreal injections of bevacizumab in the treatment of central serous chorioretinopathy. AB - PURPOSE: To evaluate the treatment of central serous chorioretinopathy (CSC) with either subthreshold diode laser MicroPulse (SDM) or intravitreal bevacizumab (BCZ). METHODS: This comparative, controlled, prospective study conducted over a period of 10 months examined 52 eyes of 52 patients with (a) treatment with SDM at the active leakage site guided by fluorescein angiography (FA) (n=16 eyes), (b) intravitreal injection of 1.25 mg BCZ (n=10 eyes), or (c) observation (n=26 eyes). Outcome measures included changes in retinal pigment epithelium (RPE) leakage at FA, central macular thickness (CMT), best-corrected visual acuity (BCVA), and 10 degrees macular perimetry. RESULTS: At the end of the study, there was 12.5% persistent leakage in the SDM, compared with 60% in the BCZ and 92% in the control group. Mean CMT decreased by 94 MUm in the SDM, 38 MUm in the BCZ, and did not change in the control group. Mean BCVA improved more than 6 early treatment of diabetic retinopathy study letters in the SDM, decreased by one letter in the BCZ, and by two letters in the control group. In the SDM group, mean perimetric deficit improved by 1.5 decibels and corrected lost variance by 2.6. In the BCZ, it improved by 0.6, and in the control group by 0.5. Retreatment was required in 7/16 eyes of the SDM group (43.75%), and in 5/10 eyes of the BCZ group (50%). CONCLUSION: SDM photocoagulation was superior to intravitreal injections of 1.25 mg BCZ in the treatment of CSC, which resulted in enhanced visual acuity and macular perimetry. PMID- 22079962 TI - Eyelid anaesthesia using tetracaine gel in the treatment of paediatric superglue tarsorrhaphy. PMID- 22079963 TI - Why we get a blue stain. PMID- 22079964 TI - Retinal nerve fiber layer and macular inner retina measurements by spectral domain optical coherence tomograph in Indian eyes with early glaucoma. AB - PURPOSE: To compare the diagnostic abilities of peripapillary retinal nerve fiber layer (RNFL) and macular inner retina (MIR) measurements by spectral domain optical coherence tomography (SD-OCT) in Indian eyes early glaucoma. METHODS: In an observational, cross-sectional study, 125 eyes of 64 normal subjects and 91 eyes of 59 early glaucoma patients underwent RNFL and MIR imaging with SD-OCT. Glaucomatous eyes had characteristic optic nerve and RNFL abnormalities and correlating visual field defects and a mean deviation of better than or equal to 6 dB on standard automated perimetry. Areas under the receiver operating characteristic curves (AUC), sensitivities at a fixed specificity and likelihood ratios (LRs) were estimated for all RNFL and MIR parameters. RESULTS: The AUCs for the RNFL parameters ranged from 0.537 for the temporal quadrant thickness to 0.821 for the inferior quadrant RNFL thickness. AUCs for the MIR parameters ranged from 0.603 for the superior minus inferior MIR thickness average to 0.908 for ganglion cell complex focal loss volume (GCC-FLV). AUC for the best MIR parameter (GCC-FLV) was significantly better (P<0.001) than that of the best RNFL parameter (inferior quadrant thickness). The sensitivities of these parameters at high specificity of 95%, however, were comparable (52.7% vs58.2%). Evaluation of the LRs showed that outside normal limits results of most of the RNFL and MIR parameters were associated with large effects on the post-test probability of disease. CONCLUSION: MIR parameters with RTVue SD-OCT were as good as the RNFL parameters to detect early glaucoma. PMID- 22079965 TI - Carbon monoxide poisoning masquerading as giant cell arteritis. PMID- 22079966 TI - Increased intraocular pressure on the first post-operative day following sutureless extracapsular cataract surgery in Africa. PMID- 22079968 TI - The influence of soft contact lenses on the intraocular pressure measurement. AB - PURPOSE: To evaluate the influence of silicone hydrogel contact lenses on the intraocular pressure (IOP) measurement using Goldmann applanation tonometry (GAT), non-contact tonometry (NCT), and Pascal dynamic contour tonometry (DCT). METHODS: We included in the study 40 eyes of 40 patients who did not have any ocular or systemic diseases or contraindications to contact lens use. We measured and recorded the IOP values of each patient using NCT without and with contact lenses (groups 1 and 2, respectively), using DCT without and with contact lenses (groups 3 and 4, respectively), and using GAT without contact lenses (group 5). RESULTS: The mean IOP value of group 1 was 14.55 +/- 2.95 mm Hg and 13.92 +/- 2.58 mm Hg in group 2. We detected no statistically significant difference between group 1 and group 2 (P=0.053). The mean IOP values for group 3 and group 4 were 16.26 +/- 2.33 mm Hg and 15.19 +/- 2.40 mm Hg, respectively. We detected a statistically significant difference between groups 3 and 4 (P=0.005). Group 5's mean IOP value was 12.97 +/- 2.65 mm Hg. IOP values measured with DCT were statistically significantly higher compared with IOP values measured with NCT and GAT (P<0.0001 and P<0.0001, respectively). Additionally, IOP values measured with NCT were statistically significantly higher compared with IOP values measured with GAT (P<0.0001). CONCLUSION: According to the results of our study, silicone hydrogel soft contact lens use does not significantly affect IOP values measured with NCT, but it affects IOP values measured with DCT. PMID- 22079969 TI - Corneal nerve alterations in acute Acanthamoeba and fungal keratitis: an in vivo confocal microscopy study. AB - PURPOSE: To study sub-basal corneal nerve alterations in patients with acute Acanthamoeba keratitis (AK) and fungal keratitis (FK), using laser in vivo confocal microscopy (IVCM). METHODS: A retrospective analysis of IVCM (Heidelberg Retina Tomograph 3/Rostock Cornea Module) images of 10 AK corneas and 4 FK corneas was performed, and the results compared with those of 10 normal and 12 acute herpetic keratitis (HK) corneas. Sub-basal corneal nerves were analyzed with respect to total number of nerves, main nerve trunks, branching pattern and total length of nerves per image, as well as tortuosity. For each variable, results for three frames were averaged and analyzed using analysis of variance. RESULTS: Total corneal nerve length was significantly (P < 0.0001) reduced in patients with AK (193.4 +/- 124.5 MUm) and FK (268.6 +/- 257.4 MUm) when compared with normal controls (3811.84 +/- 911.4 MUm). Total nerve counts in patients with AK (3.9 +/- 1.2) and FK (3.6 +/- 3.2) were significantly (P < 0.0001) decreased in comparison with normal controls (24.7 +/- 5.5). The number of main nerve trunks and nerve branching was found to be significantly lower in AK and FK corneas, when compared with controls. There was a statistically significant decrease in the above parameters when compared with HK controls. CONCLUSIONS: The sub-basal corneal nerve plexus is significantly diminished in eyes with AK and FK, as demonstrated by IVCM. These results are more profound than previously reported findings of a diminished nerve plexus in HK. PMID- 22079970 TI - Retinal pigment epithelial tear resembling retinal tear. PMID- 22079971 TI - Complications due to bovine pericardium used to cover acrylic implants after enucleation and tubes of aqueous devices. PMID- 22079972 TI - Differences in uveal melanomas between men and women from the British Isles. AB - PURPOSE: The purpose of this study is to compare uveal melanomas (UMs) in men and women. METHODS: The Liverpool Ocular Oncology Centre (LOOC) database was reviewed. Patients treated for UM at the LOOC between 1993 and 2010 were selected. Differences between sexes were identified using the chi (2)-test for categorical variables and the Mann-Whitney test for continuous variables. RESULTS: The 3380 patients comprised 1685 women and 1695 men. The tumours were considered clinically to have arisen in choroid in 89.5%, ciliary body in 5.3%, and iris in 5.2%. Tumours in women were less likely to originate in choroid (87.2 vs 91.7%; P<0.001) and showed more circumferential spread in ciliary body (P<0.001) and iris (P=0.003). Tumours in men were more likely to extend to within 3 mm of optic disc or fovea (46.3 vs 39.0%, P<0.001), showing more extensive optic-disc involvement (P<0.001). The median largest basal tumour diameter was 12.2 mm in men and 11.9 mm in women (P=0.001). The tumour thickness had a median of 4.4 mm and 3.8 mm in men and women, respectively (P=0.015). The 180 ciliary body tumours occurred in 112 women and 68 men. In these, the prevalence of extraocular spread was higher in women (19.6 vs 8.8%; P=0.052). The 175 iris melanomas were more common in women than men (103 vs 72, respectively). CONCLUSIONS: In men, UMs tend to be larger and more posterior than in women. PMID- 22079973 TI - Natural presence of NS3 protease R155K hepatitis C virus variants with decreased sensitivity to protease inhibitors. PMID- 22079974 TI - HBsAg titers in the different phases of hepatitis B infection in Syrian patients. AB - BACKGROUND AND OBJECTIVES: Little is known about hepatitis B surface antigen (HBsAg) level during the natural course of hepatitis B virus (HBV) infection. The aims of this study were to determine the HBsAg titer in the different phases of HBV infection and to evaluate for the presence of a correlation between HBsAg titers and HBV DNA levels. STUDY DESIGN: 272 HBV patients were analyzed in a cross-sectional study. The patients were classified into 4 categories: immune tolerant phase (IT, n=9), immune clearance phase (IC, n=26), low-replicative phase (LR, n=131), and HBeAg-negative hepatitis (ENH, n=106). RESULTS: Median HBsAg titers were different between each phase of CHB (p<0.001): IT (4.31log(10)IU/ml), IC (4.42log(10)IU/ml), LR (3.32log(10)IU/ml) and ENH (3.71log(10)IU/ml). Correlation of HBsAg and HBV DNA was strong in IT patients (r=0.74) and the whole group (r=0.83), moderate in the ENH phase (r=0.44) and poor in the IC (r=0.14) and the LR phases (r=0.080). CONCLUSIONS: This large study demonstrates that in HBV patients, HBsAg levels are significantly different in the different stages of the disease. A correlation between serum HBV DNA and HBsAg titers does not exist except in the IT and ENH phases. Three other studies have addressed the same issue on different genotypes and we notice that there is no concordance between the 4 studies. This leads to conclude that measurement of HBsAg level, for the time being, will not replace the serum HBV DNA as a marker of replication. PMID- 22079975 TI - J7, a methyl jasmonate derivative, enhances TRAIL-mediated apoptosis through up regulation of reactive oxygen species generation in human hepatoma HepG2 cells. AB - The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/APO2L), a member of the TNF gene superfamily, induces apoptosis upon engagement of cognate death receptors. While TRAIL is relatively non-toxic to normal cells, it selectively induces apoptosis in many transformed cells. Nevertheless, some human hepatoma cells are particularly resistant to the effects of TRAIL. In this study, we show that J7, a novel methyl jasmonate analogue, sensitizes TRAIL-resistant HepG2 human hepatocarcinoma cells to TRAIL-mediated apoptosis. Our results indicate that J7 substantially enhances TRAIL-induced apoptosis, compared with treatment with either agent alone. Combined treatment with J7 and TRAIL effectively induced Bid cleavage, down-regulation of XIAP, cIAP-1 and Bcl-xL, activation of caspases, and cleavage of poly(ADP-ribose) polymerase and phopholipase gamma-1. In addition, generation of reactive oxygen species (ROS) showed a significant increase in cells following exposure to J7 in a time dependent manner. However, the cytotoxic effects induced by co-treatment with J7 and TRAIL were markedly attenuated by caspase inhibitors, indicating an important role for caspases. Administration of N-acetyl cysteine, a scavenger of ROS, also resulted in significant inhibition of apoptosis induced by combinatory treatment with J7 and TRAIL. These results support a mechanism whereby J7 plus TRAIL induces apoptosis of HepG2 human hepatoma cells through a signaling cascade involving a ROS-mediated caspase pathway. PMID- 22079976 TI - Myelin structure is unaltered in chemotherapy-induced peripheral neuropathy. AB - PURPOSE: Alterations in mRNA for myelin proteins are reported in animal models of chemotherapy-induced peripheral neuropathies (CIPN); however, ultrastructural changes in aldehyde-fixed and plastic-embedded myelin are not evident by electron microscopy. Therefore, we used X-ray diffraction (XRD) to investigate more subtle changes in myelin sheath structure from unfixed nerves. EXPERIMENTAL DESIGN: We used in vivo chronic animal models of CIPN in female Wistar rats, administering cisplatin (CDDP 2mg/kg, i.p. twice/week), paclitaxel (PT 10mg/kg, i.v. once/week) or bortezomib (0.20mg/kg, i.v. three times/week) over a total period of 4weeks. Animal weights were monitored, and tail nerve conduction velocity (NCV) was determined at the end of the treatments to assess the occurrence of peripheral neuropathy. Sciatic nerves were collected and the myelin structure was analyzed using electron microscopy (EM) and XRD. RESULTS: All the rats treated with the chemotherapy agents developed peripheral neuropathy, as indicated by a decrease in NCV values; however, light and electron microscopy indicated no severe pathological alterations of the myelin morphology. XRD also did not demonstrate significant differences between sciatic nerves in treated vs. control rats with respect to myelin period, relative amount of myelin, membrane structure, and regularity of membrane packing. CONCLUSIONS: These results indicate that experimental peripheral neuropathy caused by CDDP, PT, and bortezomib-which are among the most widely used chemotherapy agents-does not significantly affect the structure of internodal myelin in peripheral nerve. PMID- 22079977 TI - Interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX, a solid state spectroscopy study. AB - To investigate the nature of binding of quinoline antimalarial drugs to heme and to extract experimental evidence for this binding, the interaction of ferriprotoporphyrin IX (FP) with chloroquine and quinacrine (both of which have a similar side chain) and quinoline methanol antimalarials quinine and mefloquine has been studied using IR and NIR-Raman spectroscopy in the solid state. Attenuated total reflectance infrared spectroscopic data clearly show that heme in chloroquine-FP complex is not MU-oxo dimeric indicating that the hypothesis that chloroquine binds to FP MU-oxo dimer with a stoichiometry of 1 chloroquine:2 MU-oxo dimers is not valid in the solid state. Moreover, the first vibrational spectroscopy evidence is presented for the formation of hydrogen bonding between a propionate group of heme and the tertiary amino nitrogen of chloroquine and quinacrine. Raman spectroscopy data does not provide any evidence to support the formation of a similar salt bridge in the complexes of FP with quinine and mefloquine; however, it suggests that the interaction of these drugs with FP happens through coordination of the Fe(III) center of the porphyrin to the 9 hydroxy group of the drug. PMID- 22079978 TI - Fe(III)-complexes of the tripodal trishydroxamate siderophore basidiochrome: potential biological implications. AB - One method of mobilization of iron by mycorrhizal organisms is through the secretion of small organic chelators called siderophores. Hydroxamate donor chelators are a common type of siderophore that is frequently used by fungal organisms. The primary siderophore that is produced by fungi from the genera Ceratobasidium and Rhizoctonia is the tripodal trishydroxamate siderophore basidiochrome. To gain some insight into the iron uptake mechanisms of these symbiotic fungi, the iron binding characteristics of basidiochrome were determined. It was found that basidiochrome exhibits a log beta(110) of 27.8+/ 0.1 and a pFe value of 25.0. These values are similar to those of another fungal trishydroxamate siderophore, ferrichrome. The similarity in iron affinity between the two siderophores suggests that the structure of the backbone has little influence in complex formation due to the length of the pendant arms, although the identity of the terminating groups of the pendant arms is likely related to complex stability. The role of basidiochrome in the biogeochemical cycling of iron is also discussed. PMID- 22079979 TI - MLC tracking for Elekta VMAT: a modelling study. AB - A model has been developed to simulate volumetric modulated arc therapy (VMAT) delivery for Elekta control systems. The model was experimentally validated for static-tumour VMAT delivery and has been applied to the investigation of motion compensation with dynamic multileaf collimator (dMLC) delivery tracking for a series of VMAT lung treatment plans at various control point spacings for five patients. The relative increase in treatment time with dMLC tracking was calculated for four 1D rigid-body motion trajectories, and the effect of the control point spacing, the MLC leaf speed and an increased number of dose levels on the dMLC tracking delivery time evaluated. It has been observed that a faster leaf speed is advantageous for motion trajectories with shorter time periods and larger amplitudes. The accuracy of dMLC tracking was found to increase with a decreased control point spacing and is dependent on the amplitude and time period of the motion trajectory of the target. dMLC tracking is shown to be a promising emerging technology which can confer advantage over breath-hold motion compensation techniques which more drastically reduce the efficiency of VMAT and are more invasive for the patient. PMID- 22079980 TI - Elongation factor-2, a Th1 stimulatory protein of Leishmania donovani, generates strong IFN-gamma and IL-12 response in cured Leishmania-infected patients/hamsters and protects hamsters against Leishmania challenge. AB - In visceral leishmaniasis, Th1 types of immune responses correlate with recovery from and resistance to disease, and resolution of infection results in lifelong immunity against the disease. Leishmanial Ags that elicit proliferative and cytokine responses in PBMCs from cured/exposed/Leishmania patients have been characterized through proteomic approaches, and elongation factor-2 is identified as one of the potent immunostimulatory proteins. In this study, we report the cloning and expression of Leishmania donovani elongation factor-2 protein (LelF 2) and its immunogenicity in PBMCs of cured/exposed Leishmania-infected patients and hamsters (Mesocricetus auratus). Leishmania-infected cured/exposed patients and hamsters exhibited significantly higher proliferative responses to recombinant Lelf-2 (rLelF-2) than those with L. donovani-infected hosts. The soluble L. donovani Ag stimulated PBMCs of cured/exposed and Leishmania patients to produce a mixed Thl/Th2-type cytokine profile, whereas rLelF-2 stimulated the production of IFN-gamma, IL-12, and TNF-alpha but not IL-4 or IL-10. Further, rLelF-2 downregulated LPS-induced IL-10 as well as soluble L. donovani Ag-induced IL-4 production by Leishmania patient PBMCs. The immunogenicity of rLelF-2 was also checked in hamsters in which rLelF-2 generates strong IL-12- and IFN-gamma mediated Th1 immune response. This was further supported by a remarkable increase in IgG2 Ab level. We further demonstrated that rLelF-2 was able to provide considerable protection (~65%) to hamsters against L. donovani challenge. The efficacy was supported by the increased inducible NO synthase mRNA transcript and Th1-type cytokines IFN-gamma, IL-12, and TNF-alpha and downregulation of IL-4, IL 10, and TGF-beta. Hence, it is inferred that rLelF-2 elicits a Th1 type of immune response exclusively and confers considerable protection against experimental visceral leishmaniasis. PMID- 22079981 TI - Dengue virus-induced autoantibodies bind to plasminogen and enhance its activation. AB - Dengue virus infection can lead to life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in patients. Abnormal activation of the coagulation and fibrinolysis system is one of the hallmarks associated with DHF/DSS patients. However, the mechanisms that cause pathology in DHF/DSS patients are still unclear. Because conversion of plasminogen (Plg) to plasmin (Plm) is the first step in the activation of fibrinolysis, Abs against Plg found in DHF/DSS patients may be important. Therefore, to investigate the specificity, function, and possible origin of these Abs, we generated several Plg cross reactive mAbs from DENV-immunized mice. An IgG mAb, 6H11, which recognizes an epitope associated with a dengue envelope protein, demonstrated a high level of cross-reactivity with Plg. The 6H11 Ab was further characterized with regard to its effect on Plg activation. Using Plm-specific chromogenic substrate S-2251, we found that mAb 6H11 demonstrated serine protease activity and could convert Plg directly to Plm. The serine protease activity of mAb 6H11 was further confirmed using serine protease chromogenic substrate S-2288. In addition, we found several Plg cross-reactive mAbs that could enhance urokinase-induced Plg activation. Lastly, mAb 6H11 could induce Plm activity and increase the level of D-dimer (a fibrin degradation product) in both human and mouse platelet-poor plasma. Taken together, these data suggest DENV-induced Plg cross-reactive Abs may enhance Plg conversion to Plm, which would be expected to contribute to hyperfibrinolysis in DHF/DSS patients. PMID- 22079982 TI - Activation of NLRC4 by flagellated bacteria triggers caspase-1-dependent and independent responses to restrict Legionella pneumophila replication in macrophages and in vivo. AB - Although NLRC4/IPAF activation by flagellin has been extensively investigated, the downstream signaling pathways and the mechanisms responsible for infection clearance remain unclear. In this study, we used mice deficient for the inflammasome components in addition to wild-type (WT) Legionella pneumophila or bacteria deficient for flagellin (flaA) or motility (fliI) to assess the pathways responsible for NLRC4-dependent growth restriction in vivo and ex vivo. By comparing infections with WT L. pneumophila, fliI, and flaA, we found that flagellin and motility are important for the colonization of the protozoan host Acanthamoeba castellanii. However, in macrophages and mammalian lungs, flagellin expression abrogated bacterial replication. The flagellin-mediated growth restriction was dependent on NLRC4, and although it was recently demonstrated that NLRC4 is able to recognize bacteria independent of flagellin, we found that the NLRC4-dependent restriction of L. pneumophila multiplication was fully dependent on flagellin. By examining infected caspase-1(-/-) mice and macrophages with flaA, fliI, and WT L. pneumophila, we could detect greater replication of flaA, which suggests that caspase-1 only partially accounted for flagellin dependent growth restriction. Conversely, WT L. pneumophila multiplied better in macrophages and mice deficient for NLRC4 compared with that in macrophages and mice deficient for caspase-1, supporting the existence of a novel caspase-1 independent response downstream of NLRC4. This response operated early after macrophage infection and accounted for the restriction of bacterial replication within bacteria-containing vacuoles. Collectively, our data indicate that flagellin is required for NLRC4-dependent responses to L. pneumophila and that NLRC4 triggers caspase-1-dependent and -independent responses for bacterial growth restriction in macrophages and in vivo. PMID- 22079984 TI - Cannabinoid receptor type 1 protects nigrostriatal dopaminergic neurons against MPTP neurotoxicity by inhibiting microglial activation. AB - This study examined whether the cannabinoid receptor type 1 (CB(1)) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB(1) receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB(1) receptor. The present in vivo and in vitro findings clearly indicate that the CB(1) receptor possesses anti inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson's disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage. PMID- 22079983 TI - Cutting edge: activation of virus-specific CD4 T cells throughout gamma herpesvirus latency. AB - CD4 T cells are essential for immune control of gamma-herpesvirus latency. We previously identified a murine MHC class II-restricted epitope in gamma herpesvirus-68 gp150 (gp150(67-83)I-A(b)) that elicits CD4 T cells that are maintained throughout long-term infection. However, it is unknown whether naive cells can be recruited into the antiviral CD4 T cell pool during latency. In this study, we generate a mouse transgenic for a gp150-specific TCR and show epitope specific activation of transgenic CD4 T cells during acute and latent infections. Furthermore, although only dendritic cells can stimulate virus-specific CD8 T cells during latency, we show that both dendritic cells and B cells stimulate transgenic CD4 T cells. These studies demonstrate that naive CD4 T cells specific for a viral glycoprotein can be stimulated throughout infection, even during quiescent latency, suggesting that CD4 T cell memory is maintained in part by the continual recruitment of naive cells. PMID- 22079985 TI - Resident peritoneal NK cells. AB - In this study, we describe a new population of NK cells that reside in the normal, uninflamed peritoneal cavity. Phenotypically, they share some similarities with the small population of CD49b(-), CD27(+) immature splenic NK cells, as well as liver NK cells, but they differ in their expression of CD62L, TRAIL, and EOMES. Functionally, the peritoneal NK cells resemble the immature splenic NK cells in their production of IFN-gamma, GM-CSF, and TNF-alpha and in the killing of YAC-1 target cells. We also found that the peritoneum induces different behavior in mature and immature splenic NK cells. When transferred i.v. into RAGgammac knockout mice, both populations undergo homeostatic proliferation in the spleen, but only the immature splenic NK cells are able to reach the peritoneum. When transferred directly into the peritoneum, the mature NK cells survive but do not divide, whereas the immature NK cells proliferate profusely. These data suggest that the peritoneum is not only home to a new subset of tissue resident NK cells, but that it differentially regulates the migration and homeostatic proliferation of immature versus mature NK cells. PMID- 22079986 TI - Regulation of TCRbeta allelic exclusion by gene segment proximity and accessibility. AB - Ag receptor loci are regulated to promote allelic exclusion, but the mechanisms are not well understood. Assembly of a functional TCR beta-chain gene triggers feedback inhibition of V(beta)-to-DJ(beta) recombination in double-positive (DP) thymocytes, which correlates with reduced V(beta) chromatin accessibility and a locus conformational change that separates V(beta) from DJ(beta) gene segments. We previously generated a Tcrb allele that maintained V(beta) accessibility but was still subject to feedback inhibition in DP thymocytes. We have now further analyzed the contributions of chromatin accessibility and locus conformation to feedback inhibition using two novel TCR alleles. We show that reduced V(beta) accessibility and increased distance between V(beta) and DJ(beta) gene segments both enforce feedback inhibition in DP thymocytes. PMID- 22079988 TI - Antigen targeting to plasmacytoid dendritic cells via Siglec-H inhibits Th cell dependent autoimmunity. AB - Plasmacytoid dendritic cells (PDCs) have been shown to present Ags and to contribute to peripheral immune tolerance and to Ag-specific adaptive immunity. However, modulation of adaptive immune responses by selective Ag targeting to PDCs with the aim of preventing autoimmunity has not been investigated. In the current study, we demonstrate that in vivo Ag delivery to murine PDCs via the specifically expressed surface molecule sialic acid binding Ig-like lectin H (Siglec-H) inhibits Th cell and Ab responses in the presence of strong immune stimulation in an Ag-specific manner. Correlating with sustained low-level MHC class II-restricted Ag presentation on PDCs, Siglec-H-mediated Ag delivery induced a hyporesponsive state in CD4(+) T cells leading to reduced expansion and Th1/Th17 cell polarization without conversion to Foxp3(+) regulatory T cells or deviation to Th2 or Tr1 cells. Siglec-H-mediated delivery of a T cell epitope derived from the autoantigen myelin oligodendrocyte glycoprotein to PDCs effectively delayed onset and reduced disease severity in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis by interfering with the priming phase without promoting the generation or expansion of myelin oligodendrocyte glycoprotein-specific Foxp3(+) regulatory T cells. We conclude that Ag delivery to PDCs can be harnessed to inhibit Ag-specific immune responses and prevent Th cell-dependent autoimmunity. PMID- 22079987 TI - Inducible CD4+LAP+Foxp3- regulatory T cells suppress allergic inflammation. AB - Regulatory T cells (Tregs) play a critical role in the maintenance of airway tolerance. We report that inhaled soluble Ag induces adaptive Foxp3(+) Tregs, as well as a regulatory population of CD4(+) T cells in the lungs and lung-draining lymph nodes that express latency-associated peptide (LAP) on their cell surface but do not express Foxp3. Blocking the cytokine IL-10 or TGF-beta prevented the generation of LAP(+) Tregs and Foxp3(+) Tregs in vivo, and the LAP(+) Tregs could also be generated concomitantly with Foxp3(+) Tregs in vitro by culturing naive CD4(+) T cells with Ag and exogenous TGF-beta. The LAP(+) Tregs strongly suppressed naive CD4(+) T cell proliferation, and transfer of sorted OVA-specific LAP(+) Tregs in vivo inhibited allergic eosinophilia and Th2 cytokine expression in the lung, either when present at the time of Th2 sensitization or when injected after Th2 cells were formed. Furthermore, inflammatory innate stimuli from house dust mite extract, nucleotide-binding oligomerization domain containing 2 ligand, and LPS, which are sufficient for blocking airway tolerance, strongly decreased the induction of LAP(+) Tregs. Taken together, we concluded that inducible Ag-specific LAP(+) Tregs can suppress asthmatic lung inflammation and constitute a mediator of airway tolerance together with Foxp3(+) Tregs. PMID- 22079989 TI - MIP-T3 is a negative regulator of innate type I IFN response. AB - TNFR-associated factor (TRAF) 3 is an important adaptor that transmits upstream activation signals to protein kinases that phosphorylate transcription factors to induce the production of type I IFNs, the important effectors in innate antiviral immune response. MIP-T3 interacts specifically with TRAF3, but its function in innate IFN response remains unclear. In this study, we demonstrated a negative regulatory role of MIP-T3 in type I IFN production. Overexpression of MIP-T3 inhibited RIG-I-, MDA5-, VISA-, TBK1-, and IKKepsilon-induced transcriptional activity mediated by IFN-stimulated response elements and IFN-beta promoter. MIP T3 interacted with TRAF3 and perturbed in a dose-dependent manner the formation of functional complexes of TRAF3 with VISA, TBK1, IKKepsilon, and IFN regulatory factor 3. Consistent with this finding, retinoic acid-inducible gene I- and TBK1 induced phosphorylation of IFN regulatory factor 3 was significantly diminished when MIP-T3 was overexpressed. Depletion of MIP-T3 facilitated Sendai virus induced activation of IFN production and attenuated the replication of vesicular stomatitis virus. In addition, MIP-T3 was found to be dissociated from TRAF3 during the course of Sendai virus infection. Our findings suggest that MIP-T3 functions as a negative regulator of innate IFN response by preventing TRAF3 from forming protein complexes with critical downstream transducers and effectors. PMID- 22079990 TI - The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. AB - Microglial cells are difficult to track during development because of the lack of specific reagents for myeloid subpopulations. To further understand how myeloid lineages differentiate during development to create microglial cells, we investigated CX3CR1 and CCR2 transcription unit activation in Cx3cr1(+/GFP)CCR2(+/RFP) knockin fluorescent protein reporter mice. The principal findings include: 1) CX3CR1(+) cells localized to the aorta-gonad-mesonephros region, and visualized at embryonic day (E)9.0 in the yolk sac and neuroectoderm; 2) at E10.5, CX3CR1 single-positive microglial cells were visualized penetrating the neuroepithelium; and 3) CX3CR1 and CCR2 distinguished infiltrating macrophages from resident surveillant or activated microglia within tissue sections and by flow cytometric analyses. Our results support the contribution of the yolk sac as a source of microglial precursors. We provide a novel model to monitor chemokine receptor expression changes in microglia and myeloid cells early (E8.0-E10.5) in development and during inflammatory conditions, which have been challenging to visualize in mammalian tissues. PMID- 22079991 TI - Uterine environment as a regulator of birth weight and body dimensions of newborn lambs. AB - Pure-bred embryos were transferred within and reciprocally between large (Suffolk) and small (Cheviot) breeds of sheep to establish 4 treatment groups: SinS (Suffolk embryos in Suffolk dams), SinC (Suffolk embryos in Cheviot dams), CinS (Cheviot embryos in Suffolk dams), and CinC (Cheviot embryos in Cheviot dams). The recipient ewes carried single fetuses to term. The maternal plasma concentrations of ovine placental lactogen (oPL), progesterone, IGF-1, FFA, and glucose were measured on d 50, 90, 120, and 140 of pregnancy. Birth weight, body dimensions, and placental characteristics of lambs were recorded at birth. There was a recipient ewe breed * lamb breed * time interaction for the concentration of oPL (P = 0.03), but no such interaction was observed for progesterone (P = 0.42), IGF-1 (P = 0.57), glucose (P = 0.36), or FFA (P = 0.72). There were no differences in oPL (P = 0.28) and progesterone (P = 0.34) concentrations between SinC and SinS ewes. The concentrations of FFA on d 140 (P = 0.008), and those of glucose on d 50 (P = 0.02) and 120 (P = 0.01), were greater in SinC ewes than in SinS ewes. The ewes in CinS had less FFA concentration (P = 0.002) at all time points than CinC ewes. The concentrations of IGF-1 on d 90 were greater (P = 0.004) in CinS ewes than CinC ewes, but did not differ (P = 0.16) on d 50, 120, and 140. The concentrations of glucose on d 50 (P = 0.001), 90 (P = 0.03), and 140 (P = 0.03) were less in CinS ewes compared with CinC ewes. The birth weight of SinC lambs (5.04 +/- 0.20 kg) was lighter (P = 0.001) than SinS lambs (5.94 +/ 0.19 kg), and body dimensions of SinC lambs were smaller (P = 0.01) than SinS lambs. Neither birth weight nor the body dimensions of CinS lambs differed (P = 0.24) from CinC lambs. Cotyledon number was reduced (P = 0.04) in the CinS (57.5 +/- 6.3) compared with the SinS group (74.2 +/- 5.9), whereas mean cotyledon weight in CinS (2.42 +/- 0.20 g) was greater (P = 0.02) than SinS (1.74 +/- 0.21 g). It was concluded that the large genotype lambs were lighter and smaller when born to small genotype dams; however, the birth weight or body dimensions of small genotype lambs did not differ when born to large genotype dams. This study suggests that plasma oPL, progesterone, IGF-1, FFA, and glucose concentrations at different times throughout pregnancy reflect the regulatory effect of the uterine environment on the development of the fetus. PMID- 22079992 TI - Effect of dietary conjugated linoleic acid on marbling and intramuscular adipocytes in pork. AB - Dietary CLA has been reported to decrease backfat and increase marbling in pigs. Our objective was to determine whether the increase in marbling involved changes in intramuscular adipocyte number or size or both. Twenty barrows (53 kg) were penned in pairs and pens were randomly assigned to receive diets containing either 1% soybean oil (SBO) or CLA (60% CLA isomers) for 6 wk. Body weight and feed intake were determined weekly. At slaughter, loin samples were obtained and flash frozen for RNA extraction and real-time reverse-transcription PCR analysis of gene expression. After a 24-h chill, loin eye area and backfat depth were measured and subjective marbling and color scores were assigned. Loin, backfat, and belly fat samples were obtained for fatty acid analysis by gas chromatography. Loin samples were also frozen in ice-cold isopentane for histological analysis of intramuscular adipocytes. Dietary CLA did not affect BW or feed intake at any point (P > 0.10), nor did treatment groups differ in HCW (P = 0.417) or loin color (P = 0.500). The CLA-fed pigs did have less (P = 0.018) backfat and smaller (P = 0.047) loin eye area than SBO-fed pigs and had a trend for an increase (P = 0.069) in marbling score. Relative gene expression for markers of preadipocytes (preadipocyte factor 1; Pref-1), differentiating adipocytes (PPARgamma), and mature adipocytes [fatty acid binding protein 4 (FABP4) and perilipin (PLIN)] were determined and normalized to the expression of acidic ribosomal phosphoprotein. No significant differences were detected, but the expression of PPARgamma (P = 0.265), PLIN (P = 0.265), and FABP4 (P = 0.148) was numerically greater in CLA-fed pigs than in SBO-fed pigs. Loin samples were stained with Oil Red O to identify intramuscular adipocytes. The average cell area was increased (P = 0.030) in CLA-fed pigs. The cis-9,trans-11 and trans 10,cis-12 CLA isomers were incorporated (P = 0.006) into backfat and belly fat, but only trans-10,cis-12 CLA was increased in the loin (P = 0.004) of CLA-fed pigs. The proportion of SFA was increased (P = 0.006) by CLA in all tissues. These results indicate that the increase in marbling in pigs fed CLA may be related to increased intramuscular adipocyte size, and the combination of increased marbling and degree of saturation could improve the eating quality of CLA-fed pork. PMID- 22079993 TI - Energy use in pig production: an examination of current Iowa systems. AB - This paper compares energy use for different pig production systems in Iowa, a leader in US swine production. Pig production systems include not only the growth and performance of the pigs, but also the supporting infrastructure of pig production. This supporting infrastructure includes swine housing, facility management, feedstuff provision, swine diets, and manure management. Six different facility type * diet formulation * cropping sequence scenarios were modeled and compared. The baseline system examined produces 15,600 pigs annually using confinement facilities and a corn-soybean cropping sequence. Diet formulations for the baseline system were corn-soybean meal diets that included the synthetic AA l-lysine and exogenous phytase. The baseline system represents the majority of current US pork production in the Upper Midwest, where most US swine are produced. This system was found to require 744.6 MJ per 136-kg market pig. An alternative system that uses bedded hoop barns for grow-finish pigs and gestating sows would require 3% less (720.8 MJ) energy per 136-kg market pig. When swine production systems were assessed, diet type and feed ingredient processing were the major influences on energy use, accounting for 61 and 79% of total energy in conventional and hoop barn-based systems, respectively. Improving feed efficiency and better matching the diet formulation with the thermal environment and genetic potential are thus key aspects of reducing energy use by pig production, particularly in a hoop barn-based system. The most energy intensive aspect of provisioning pig feed is the production of synthetic N for crop production; thus, effectively recycling manure nutrients to cropland is another important avenue for future research. Almost 25% of energy use by a conventional farrow-to-finish pig production system is attributable to operation of the swine buildings. Developing strategies to minimize energy use for heating and ventilation of swine buildings while maintaining pig comfort and performance is a third critical area for future research. The hoop barn-based alternative uses 64% less energy to operate buildings but requires bedding and 2.4% more feed. Current Iowa pig production systems use energy differently but result in similar total energy use. Compared with 1975, current farrow-to-finish systems in Iowa require 80% less energy to produce live market pigs. PMID- 22079994 TI - Standardized ileal digestible tryptophan-to-lysine ratios in growing pigs fed corn-based and non-corn-based diets. AB - Two 21-d experiments were conducted to determine the optimum standardized ileal digestible (SID) Trp:Lys in growing pigs fed corn-based diets compared with non corn-based diets. The primary response variables in both experiments were ADG and plasma urea N (PUN) concentrations with the optimum SID Trp:Lys determined using broken-line analysis. Experiment 1 evaluated the optimum SID Trp:Lys in growing pigs fed corn-based diets consisting primarily of corn with minor inclusion of Canadian field peas and corn gluten meal to keep the SID Trp:Lys low. This experiment used 120 crossbred pigs (initial BW: 25.73 +/- 2.46 kg) that were blocked by sex and initial BW and allotted to 5 SID Trp:Lys with 5 pens each for the first 4 treatments and 4 pens for the last treatment and 5 pigs/pen. Diets were formulated by the addition of supplemental Trp to create various SID Trp:Lys (12.77, 14.07, 15.50, 16.91, and 17.94%) with a constant SID Lys of 0.66%, which was determined to be 83% of the Lys requirement for pigs at this location. As the SID Trp:Lys increased from 12.77 to 17.94%, ADG increased (0.562, 0.648, 0.788, 0.787, and 0.815 kg/d) linearly (P < 0.001) and quadratically (P = 0.009), resulting in an optimum SID Trp:Lys of 15.73% (P < 0.001). Plasma urea N decreased (10.43, 9.30, 8.21, 8.55, and 9.25 mg/dL) linearly (P = 0.069) and quadratically (P = 0.015), resulting in an optimum SID Trp:Lys of 15.83% (P = 0.007). Experiment 2 evaluated the optimum SID Trp:Lys in growing pigs fed non corn-based diets consisting primarily of barley and Canadian field peas, with smaller proportions of corn and wheat. Experiment 2 used 120 crossbred pigs (initial BW: 28.49 +/- 2.92 kg) that were allotted to 5 increasing SID Trp:Lys (13.05, 14.32, 15.59, 16.85, and 18.11%; 0.66% SID Lys) in the same manner as Exp. 1. As SID Trp:Lys increased in Exp. 2, ADG increased linearly (P = 0.007) with the optimum SID Trp:Lys of 15.99% (P = 0.048). Plasma urea N concentrations decreased linearly (P = 0.056) and quadratically (P = 0.067) as SID Trp:Lys increased, resulting in an optimum SID Trp:Lys of 15.29% (P = 0.009). Averaging the break point values for ADG and PUN obtained from broken-line analysis for Exp. 1 and 2 produced optimum SID Trp:Lys of 15.78 and 15.64%, respectively. Based on the results from these 2 experiments, it seems that the optimum SID Trp:Lys is virtually unaffected by the dietary feedstuffs used as long as the diets are formulated on an SID AA basis. PMID- 22079995 TI - Improvement of growth performance and sanitary status of weaned piglets fed a bovine colostrum-supplemented diet. AB - The present study investigated the effect of 3 different durations of feeding a diet supplemented with defatted bovine colostrum (Col) on growth performance and sanitary status of the weaned piglet. At 28 d of age, piglets were weaned and fed 1 of the 2 following diets: a control (Ctrl) starter diet or a starter diet supplemented with Col. Two experiments were conducted. In Exp. 1, 310 piglets (12 pens consisting of 10 piglets/pen and 10 pens consisting of 19 piglets/pen) were allocated to 1 of the 2 dietary treatments for 12 d. In Exp. 2, 522 piglets (18 pens consisting of 10 piglets/pen and 18 pens consisting of 19 piglets/pen) were allocated to 1 of the following 3 dietary treatments: fed the Ctrl diet from d 1 to 12 (Ctrl), Col diet from d 1 to 4 and then the Ctrl diet up to d 12 (Col-4d), or the Col diet from d 1 to 6 and then the Ctrl diet up to d 12 (Col-6d). For both experiments, a commercial second-phase diet was fed to piglets from d 12 to 46. Feed intake, growth performance, and cleanliness of floor and hindquarters of animals were investigated during the first 7 wk postweaning. In Exp. 1, from d 0 to 12, ADFI, ADG, and G:F were 16 (P = 0.004), 23 (P < 0.001), and 5% (P = 0.069) greater, respectively, in Col piglets compared with Ctrl piglets. Thereafter, ADFI and ADG were 7 (P < 0.001) and 9% (P < 0.001) greater, respectively, in Col piglets than Ctrl piglets (d 12 to 46). On d 12 after weaning, piglets fed the Col diet had more normal feces (+13%) and less soft or liquid feces (-9 and -4%, respectively) than piglets fed the Ctrl diet (P = 0.06). Compared with Ctrl piglets, feeding the Col diet led to more days with normal feces for the floor cleanliness (+22%; P < 0.001) from d 7 to 11. In Exp. 2, compared with Ctrl piglets, ADFI, ADG, and G:F were 8, 23, and 13% greater (P < 0.05) in Col-6d piglets from d 0 to 9, whereas values for Col-4d piglets were intermediate and did not differ from the values of the other dietary treatments. On d 9 after weaning, piglets fed the Col-4d or the Col-6d diet had more normal feces (+6 and +4%, respectively) and less liquid feces (-4 and -3%, respectively) than piglets fed the Ctrl diet (P = 0.08). No long lasting effects were observed thereafter. In conclusion, there was a reduction of weaning-induced growth check and diarrheal episodes in weaned piglets fed the Col diet. The beneficial effects of the bovine colostrum were observed beyond the period of treatment when the supplementation covered the first 6 d postweaning, which corresponded to the acute phase of postweaning digestive disturbances. PMID- 22079996 TI - Growth and Development Symposium: Inflammation: Role in the etiology and pathophysiology of clinical mastitis in dairy cows. AB - Genetic selection for increased milk production in dairy cattle was not associated with an attenuated inflammatory response. The systemic and local inflammatory responses contribute to altered metabolism, reduced production performance, and increased cull rate of lactating dairy cows with clinical mastitis. More aggressive inflammatory responses were observed during the peripartum period when compared with cows in late lactation after an intramammary challenge with purified lipopolysaccharide. The epidemiology of clinical mastitis indicates that the greatest incidence is observed during the peripartum period; therefore, an enhanced inflammatory response with concomitant suppression in other immune responses may be involved in the etiology and severity of the clinical mastitis observed in peripartum cows. Milk production losses and compositional changes are observed among all mammary quarters from a cow with clinical mastitis, but the responses are more severe and sustained among infected quarters. The infected mammary quarters reflect both the systemic and local reactions, whereas uninfected quarters represent only the systemic response. The systemic effects of the inflammatory response include reduced DMI, hyperthermia, and changes in whole-body nutrient partitioning affecting mammary epithelial substrate availability, whereas local inflammatory effects include energetic requirements of the increased inflammatory leukocyte pool, decreased synthetic capacity of mammary epithelium independent of substrate availability, and paracellular leakage of milk components from the alveolar lumen into the extracellular fluid. Research has focused on improving host immunological defenses, attenuating the inflammatory response, or improving the resolution of the disease state to limit the deleterious effects during clinical mastitis. This paper highlights the role inflammation plays in the etiology and pathophysiology of clinical mastitis as well as potential management strategies to reduce or prevent those losses. PMID- 22079997 TI - Zilpaterol hydrochloride alters abundance of beta-adrenergic receptors in bovine muscle cells but has little effect on de novo fatty acid biosynthesis in bovine subcutaneous adipose tissue explants. AB - We predicted that zilpaterol hydrochloride (ZH), a beta-adrenergic receptor (AR) agonist, would depress mRNA and protein abundance of beta-AR in bovine satellite cells. We also predicted that ZH would decrease total lipid synthesis in bovine adipose tissue. Bovine satellite cells isolated from the semimembranosus muscle were plated on tissue culture plates coated with reduced growth factor matrigel or collagen. Real-time quantitative PCR was used to measure specific gene expression after 48 h of ZH exposure in proliferating satellite cells and fused myoblasts. There was no effect of ZH dose on [(3)H]thymidine incorporation into DNA in proliferating myoblasts. Zilpaterol hydrochloride at 1 uM decreased (P < 0.05) beta1-AR mRNA, and 0.01 and 1 uM ZH decreased (P < 0.05) beta2-AR and beta3 AR mRNA in myoblasts. The expression of IGF-I mRNA tended to increase (P = 0.07) with 1 uM ZH. There was no effect (P > 0.10) of ZH on the beta-AR or IGF-I gene expression in fused myotube cultures at 192 h or on fusion percentage. The beta2 AR antagonist ICI-118, 551 at 0.1 uM attenuated (P < 0.05) the effect of 0.1 uM ZH to reduce expression of beta1- and beta2-AR mRNA. The combination of 0.01 uM ZH and 0.1 uM ICI-118, 551 caused an increase (P < 0.05) in beta1-AR gene expression. There was no effect (P > 0.10) of ICI-118, 551 or ZH on beta3-AR or IGF-I. Western blot analysis revealed that the protein content of beta2-AR in ZH treated myotube cultures decreased (P < 0.05) relative to control. Total lipid synthesis from acetate was increased by ZH in bovine subcutaneous adipose tissue explants in the absence of theophylline but was decreased by ZH when theophylline was included in the incubation medium. These data indicate that ZH alters mRNA and protein concentrations of beta-AR in satellite cell cultures, which in turn could affect responsiveness of cells to prolonged ZH exposure in vivo. Similar to other beta-adrenergic agonists, ZH had only modest effects on lipid metabolism in adipose tissue explants. PMID- 22079998 TI - Alpharma Beef Cattle Nutrition Symposium: nutrition and the genome. AB - It has long been appreciated that animals fed the same diet may perform differently. This is due to the ability of nutrients to interact with and affect molecular pathways that result in differences in BW gain, production performance, or disease resistance. To understand these effects, studies are being undertaken to discover how the differential expression and function of genes occur with different diets. These studies are using new technologies, genomic resources, and analysis techniques that have recently become available for domestic animals. Nutrigenomics and nutrigenetics are new research approaches that strive to optimize health by looking beyond the diet to understand the effects of food at the genetic and epigenetic levels. Nutrigenomics is focused on the effects of diet on health through an understanding of how bioactive chemicals in foods and supplements alter gene expression or the structure of the genome of an animal. Nutrigenetics focuses on how the genetic composition (i.e., genetic variation) of an animal influences their response to a given diet. Results from these studies will aid in formulating nutritionally appropriate diets that may be optimized for animals based on their genomic underpinnings. Nutrigenomics and nutrigenetics unite many fields: nutrition, bioinformatics, molecular biology, genomics, functional genomics, epidemiology, and epigenomics. The use of multi-disciplinary tools promises new opportunities to investigate the complex interactions of the genome and the diet of an animal. Through these new approaches, the partnerships of the genome and nutrition will be revealed resulting in improved efficiency of diets, enhanced sustainability of animals as a protein source, and improved methods for preventing illnesses. PMID- 22079999 TI - Sudden death and lipomatous infiltration of the heart involved by fat necrosis resulting from acute pancreatitis. AB - The possible causal link between damage to the heart and acute pancreatitis and other pancreatic diseases has been considered in both adults and children, particularly in cases of sudden, unexpected death. However, the cardiac pathological findings so far reported in the literature are neither specific enough, nor of a kind to prove a direct pancreatic pathogenesis. We describe the occurrence of steatonecrosis developed in areas of lipomatous infiltration of the heart following acute exacerbation of latent chronic pancreatitis. The presence of mature adipocytes in the myocardium is an adequate substrate for the pancreatic lipase to give rise to the steatonecrosis, which is a well-known marker of acute pancreatitis. As far as we are aware, this is the first reported case of heart steatonecrosis in the literature. PMID- 22080000 TI - Tearing of knicker fabrics. AB - In Dunedin (South Island, New Zealand), a sexual assault is reported to police approximately once every two to three weeks, with some reports fictitious. Identifying a fictitious claim is difficult, and damage to apparel, especially knickers, may be the only form of evidence. In this paper, the tear behaviour of three knit fabrics, typical of those used to manufacture knickers is reported: the effect of laundering prior to tearing was considered. Tearing behaviour was determined using an Instron universal testing machine (Model 4464) operating in tensile mode to eliminate variability which is inevitable with human participants. Cotton and cotton-rich fabrics were more difficult to tear than modal-rich fabrics: the addition of elastane increased the time for the tear initiation as elastane fibres allowed the fabric to extend more before breaking. Specimens behaved differently depending on which direction they were torn (course direction specimens down the length of the specimen, wale-direction specimens 50% down the length, 50% across the specimen). Laundered fabrics required less force to tear than new fabrics, therefore, when examining torn apparel, the fibre content and age of the garment need to be considered. Torn fibre ends appeared similar to those damaged by other means (e.g. knife, screwdriver) and no features visible under FESEM could be attributed solely to tearing damage in the fabrics studied. PMID- 22080003 TI - Ketamine: a familiar drug we trust. PMID- 22080004 TI - Effects of in ovo injection of carbohydrates on somatic characteristics and liver nutrient profiles of broiler embryos and hatchlings. AB - Effects of the in ovo injection of commercial diluent supplemented with dextrin or with dextrin in combination with various other carbohydrates on the somatic characteristics and liver nutrient profiles of Ross * Ross 708 broiler embryos and chicks were investigated. Results include information concerning the gluconeogenic energy status of the liver before and after hatch. Eggs containing live embryos were injected in the amnion on d 18 of incubation using an automated multiple-egg injector for the delivery of the following carbohydrates dissolved in 0.4 mL of commercial diluent: 1) 6.25% glucose and 18.75% dextrin; 2) 6.25% sucrose and 18.75% dextrin; 3) 6.25% maltose and 18.75% dextrin; and 4) 25% dextrin. Also, a noninjected control and a 0.4-mL diluent-injected control were included. Body weight relative to set egg weight on d 19 of incubation (E19) was increased by the injection of all carbohydrate solutions, and on the day of hatch was increased by the injection of diluent, sucrose and dextrin, and maltose and dextrin solutions. Hatchability of the fertilized eggs, residual yolk sac weight, and liver weight were not affected by any injection treatment; however, as compared with the 0.4 mL diluent-injected group, all of the supplementary carbohydrates, except for the glucose and dextrin combination group, increased liver glycogen and glucose concentrations on E19. Furthermore, all carbohydrates, except for the 25% dextrin treatment, decreased liver fat concentration on E19. From E19 to the day of hatch, liver glycogen concentrations dropped dramatically from an average of 3.2 to 0.6%. Despite treatment differences observed on E19 for liver glycogen, glucose, and fat concentrations, these differences were lost by the day of hatch. Nevertheless, liver glycogen and glucose concentrations were positively correlated on the day of hatch. In conclusion, the in ovo injection of various supplemental carbohydrates dissolved in 0.4 mL of commercial diluent altered the liver nutrient profile of Ross * Ross 708 broiler embryos before hatch. However, the subsequent pattern of energy utilization during the hatching process modified these effects. PMID- 22080005 TI - Broiler breeder manure phosphorus forms are affected by diet, location, and period of accumulation. AB - Phosphorus (P) modifications of poultry diets have successfully decreased the total P (TP) in manures, but the effects on manure water-soluble P (WSP(M)) remain unclear. Our objectives were to characterize P forms in broiler breeder manures as affected by dietary P modification, location within the pen, and manure accumulation period. Two diets were formulated with and without phytase to attain 0.40% available P (AvP) during the breeder laying phase (22-64 wk of age). Manure was collected after accumulation periods of 48 h, 3 wk, and 39 wk in locations under the feeder and drinker and under the common area (between the feeder and drinker) of the pen. The TP, WSP(M), orthophosphate, and phytate in manure were measured. Broiler breeders that were fed phytase with a simultaneous reduction in nonphytate P (NPP) produced manures with 15% lower TP than those fed a traditional diet, but did not change WSP(M) when averaged over manure accumulation periods and locations within the pen. Regardless of diet, location within the pen, or accumulation period (r(2) = 0.76), the WSP(M) increased linearly as the manure moisture increased. As manure accumulation periods increased (48 h, 3 wk, and 39 wk), TP manure concentrations increased (11.9, 13.2, and 17.3 g/kg, respectively), orthophosphate proportions increased (73.2, 80.1, and 91.0%, respectively), and phytate proportions decreased (23.1, 17.0, and 6.7%, respectively). The mineralization of phytate and other organic complexes, which drive off carbon dioxide, presumably contributed to the increased orthophosphate and TP concentrations. Keeping breeder manures dry helps to avoid the mineralization of phytate to orthophosphate; this mineralization increased WSP(M) in our study, and thus increased the potential for elevated P loss in runoff when surface applied. PMID- 22080006 TI - Effects of monochromatic light on mucosal mechanical and immunological barriers in the small intestine of broilers. AB - Our previous studies demonstrated that green and blue monochromatic lights were effective to stimulate immune response of the spleen in broilers. This study was designed to investigate the effects of monochromatic light on both gut mucosal mechanical and immunological barriers. A total of 120 Arbor Acre male broilers on post-hatching day (P) 0 were exposed to red light, green light (GL), blue light (BL), and white light (WL) for 49 d, respectively. As compared with broilers exposed to WL, the broilers exposed to GL showed that the villus height of small intestine was increased by 19.5% (P = 0.0205) and 38.8% (P = 0.0149), the crypt depth of small intestine was decreased by 15.1% (P = 0.0049) and 10.1% (P = 0.0005), and the ratios of villus height to crypt depth were increased by 39.3% (P < 0.0001) and 52.5% (P < 0.0001) at P7 and P21, respectively. Until P49, an increased villus height (33.6%, P = 0.0076), a decreased crypt depth (15.4%, P = 0.0201), and an increased villus height-to-crypt depth ratio (58.5%, P < 0.0001) were observed in the BL group as compared with the WL group. On the other hand, the numbers of intestinal intraepithelial lymphocytes (27.9%, P < 0.0001 and 37.0%, P < 0.0001), goblet cells (GC, 22.1%, P < 0.0001 and 18.1%, P < 0.0001), and IgA(+) cells (14.8%, P = 0.0543 and 47.9%, P = 0.0377) in the small intestine were significantly increased in the GL group as compared with the WL group at P7 and P21, respectively. The numbers of intestinal intraepithelial lymphocytes (36.2%, P < 0.0001), GC (26.5%, P < 0.0001), and IgA(+) cells (68.0%, P = 0.0177) in the BL group were also higher than those in the WL group at P49. These results suggest that both mucosal mechanical and immunological barriers of the small intestine may be improved by rearing broilers under GL at an early age and under BL at an older age. PMID- 22080007 TI - Two maternal origins of Chinese domestic goose. AB - China is particularly rich in goose genetic resources. Systematic study of the genetic diversity and origin of Chinese domestic geese will provide an important scientific basis for the conservation and utilization of these resources and for human history. The 521-bp control region (D-loop) of mitochondrial DNA from 26 goose breeds and 6 Landaise geese were sequenced. The results showed that the average haplotype diversity and nucleotide diversity of Chinese domestic geese were 0.1384 and 0.00029, respectively. Shared haplotype analysis and systematic evolution analysis revealed that Chinese domestic geese had 2 maternal origins. The Yili goose breed originated from the Greylag goose (Anser anser), and the other 25 domestic goose breeds originated from the swan goose (Anser cygnoides). An interesting finding was that 1 Linxian white goose and 1 Wanxi white goose shared the same H4 haplotype with the Rhine goose and the Landaise goose, which originated from the Greylag goose (A. anser). Further research on this finding is planned. PMID- 22080008 TI - Genetic diversity of the major histocompatibility complex region in commercial and noncommercial chicken flocks using the LEI0258 microsatellite marker. AB - Microsatellite marker LEI0258 was used as an indicator to examine the variability of the major histocompatibility complex (MHC) region in 2 commercial layer flocks, 1 experimental layer cross, and 5 noncommercial flocks (used for free-run and free-range meat and egg production). We hypothesized that the populations from noncommercial sources may have more diversity in MHC genes than that in the commercial-source populations. Two related parameters, heterozygosity and the number of alleles harbored by a population, were used to assess the genetic variability. The different combinations of the 22 alleles created 66 genotypes in the 8 chicken populations that were studied. The noncommercial populations, except for the Silkies (SK), harbored more alleles than those in the 2 commercial populations, Lohmann Brown and Lohmann White. The observed heterozygosity of the MHC region was high in all of the populations, except for SK. Considering the 2 parameters we have examined, we can generalize that the intensively selected commercial egg-layer varieties seem to have less genetic variability in their MHC regions compared with that of the noncommercial flocks, which are less intensively selected. The LEI0258 variants can be used as markers to detect most of the MHC haplotypes, but in the different populations the same allele size may not always be associated with the same serologically defined haplotype. The information obtained from this study will be useful for genetic resource conservation and the development of breeding stocks that are suitable for free range production. PMID- 22080009 TI - Low-density lipoprotein receptor-related protein 2 gene is associated with egg quality traits in dwarf layers. AB - Some members of the low-density lipoprotein receptor (LDLR) family play important roles in the regulation of lipoprotein metabolism and egg quality traits. Low density lipoprotein receptor-related protein 2 (LRP2) gene belongs to the LDLR super family, and widely expresses in many tissues. This work identified and genotyped 1 single-nucleotide polymorphism (SNP), T14347C, at 3'-UTR of the LRP2 using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS), and analyzed the effects of the SNP (T14347C) on egg quality traits in 544 dwarf hens from 44 sire families. Frequencies of this SNP in the studied population did not agree with the Hardy-Weinberg equilibrium (P < 0.0001). Egg weight, albumen weight, albumen height, and albumen ratio of the TT genotype were significantly higher than those of the CC genotype (P < 0.05), whereas eggshell ratio of the TT genotype was significantly lower than that of the CC genotype (P < 0.05). The relative expression level of the LRP2 gene in the magnum was determined by real-time quantitative PCR. The gene expression of genotype CC individuals was significantly higher than that of TT and CT birds (P < 0.05). By combining both genetic effects and expression analyses results, we propose that the LRP2 gene is a good candidate gene, exhibiting a key role in albumen formation processes. PMID- 22080010 TI - The influence of antibiotics on B-cell number, percentage, and distribution in the bursa of Fabricius of newly hatched chicks. AB - Antibiotics are commonly used to prevent and treat poultry microbial infections, but certain antibiotic families depress humoral immunity, such as antibody production. Poultry humoral immunity depends on the normal functioning of the bursa of Fabricius and the B lymphocytes that mature in that gland. In this study, recommended therapeutic doses of enrofloxacin, florfenicol, or ceftiofur were administered to 2-d-old chicks. On d 7 post-hatch, bursae were sampled for histological, immunohistochemical, and flow cytometric determination of Bu-1 positive (Bu-1+) cell number, percentage, and distribution. The bursa of Fabricius from all treatment and control groups had normal morphology. The administration of antibiotics significantly decreased the number of Bu-1+ cells in the bursal medulla, with a simultaneous increase of these cells in the cortex. Flow cytometry revealed a significant decrease in the percentage of bursal Bu-1+ cells from all of the studied antibiotics: enrofloxacin (93.91 +/- 3.27), florfenicol (87.84 +/- 7.14), and ceftiofur (89.16 +/- 5.68) compared with that of the control (96.48 +/- 2.60). The combination of reduced percentages of Bu-1+ cells and a decrease in these cells in the medullary region suggests lower B cell maturation. PMID- 22080011 TI - Maternal antibody transfer to broiler progeny varies among strains and is affected by grain source and cage density. AB - Two experiments were conducted to examine the effects of broiler breeder dietary grain source and cage density on maternal antibody (MatAb) transfer to progeny in 2 genetic strains (A and B). Broiler breeders were assigned to 16 litter floor pens and fed either corn- or wheat-based diets. Breeders were administered 4 live vaccines against Newcastle disease virus (NDV). At 23 wk of age, pullets and cocks, which reflected the full BW distribution from each treatment, were moved to a cage breeder house and placed at 1 or 2 hens/cage. Breeders were artificially inseminated at 44 wk (experiment 1) and 52 wk of age (experiment 2). Eggs were collected for 8 d, incubated, and placed in individual pedigree bags at d 19 of incubation. Blood samples from 5 chicks per treatment combination were collected at hatch in both experiments. Spleen and bursa were collected from the same chicks for histomorphometry analyses in experiment 2. In the second experiment, 12 chicks per treatment were placed in cages. Progeny were provided diets based on the same grain (corn or wheat) as their parents. Serum samples were collected at 5, 9, and 13 d of age and analyzed for anti-NDV MatAb. Data were analyzed as a 2 * 2 * 2 factorial design considering strain, dietary grain source, and cage density as main factors. Interaction effects were observed in breeders and progeny. Experiment 1 showed that strain A chicks had lower levels of MatAb when hens were housed at 2 hens/cage rather than 1 hen/cage. The MatAb levels of strain B chickens were not affected by cage density in either experiment. Experiment 2 demonstrated similar effects of cage density on MatAb levels and the area of bursa follicles for both strains. Progeny of breeders fed corn-based diets had smaller spleen white pulp only when hens were housed at 2 hens/cage compared with 1 hen/cage. The results of these experiments suggest that breeder strain and cage-density conditions affected MatAb transfer to progeny and embryo development of spleen and bursa. PMID- 22080012 TI - Effects of immune stress on growth performance, immunity, and cecal microflora in chickens. AB - Immune stress is the loss of immune homeostasis by external forces. This study investigated the effects of different types of immune stress on growth performance, immunity, and the distribution of cecal microflora in broiler chickens. In total, 540 one-day-old Cobb 500 broilers were randomly assigned to receive 1 of 5 (n = 108 birds/group) treatments: 1) no vaccination; 2) simplified vaccination, which included the infectious bronchitis vaccine (H120), the inactivated avian influenza vaccine (AI), the live vaccine strain Clone-30 of the Newcastle disease virus (NDV), and the combined inactive vaccine for infectious bursal diseases and the Newcastle disease vaccine (ND-IB); 3) normal vaccination (simplified vaccination + second dose of ND-IB, H120, and AI); 4) lipopolysaccharide (LPS) stress (normal vaccination+LPS); or 5) cyclophosphamide (CPM) stress (normal vaccination+CPM).The results showed that the average BW and average feed intake decreased significantly after treatment with LPS or CPM (P < 0.05). Chickens that were challenged by LPS or CPM had a lower ileal CP digestibility than that of the control group (P < 0.01). Compared with the control group, the levels of secreted IgA decreased significantly at 42 d of age in the chickens that were treated with LPS or CPM (P < 0.01). The proliferation of the peripheral blood mononuclear cell and the levels of serum IgG in the LPS challenged chickens were higher than those in the control group chickens at 21 and 42 d of age, respectively (P < 0.05). Six clusters were identified at 21 d of age, but cluster 6 was a single sample. Only 5 clusters were identified at 42 d of age. The enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprints of the cecal samples from the no vaccination and the simplified vaccination groups clustered together with high coefficients. The ERIC-PCR fingerprints of the 3 cecal samples from the CPM and LPS treatment groups clustered together with high coefficients among them. The ERIC-PCR fingerprints of the microbial flora of the cecal contents revealed the potential effects of immune stress on the microbial populations of treated birds. These data suggest that broilers with simplified vaccinations or without vaccinations can achieve the same growth performance as broilers with general vaccinations, but immune stress can break the homeostasis of cecal microflora and impair intestinal mucosal immune function. PMID- 22080013 TI - The role of type-2 turkey astrovirus in poult enteritis syndrome. AB - An experimental study was conducted to determine the comparative pathogenicity of type-2 turkey astrovirus (TAstV-2) obtained from turkey flocks afflicted with poult enteritis syndrome (PES) and from turkey flocks displaying no apparent signs of infection. In total, ninety 7-d-old poults, which tested negative for the presence of astrovirus, rotavirus, coronavirus, and reovirus by reverse transcriptase (RT) PCR , were divided evenly into 3 groups: A, B, and C. Birds in group A were inoculated orally with turkey astrovirus-positive intestinal contents from birds affected with PES. Group B received turkey astrovirus containing intestinal contents from apparently healthy flocks. Group C served as a negative control and was given PBS. Clinical signs of diarrhea, depression, and dullness were observed in group A. Birds in group B also showed clinical signs similar to those in group A, although the signs were milder in nature. Birds in group C did not show any clinical signs. At 16 d postinoculation, the BW of birds in group A was significantly lower than that of birds in groups B or C. In addition, the bursa size was reduced in group A, but not in groups B or C. Birds in groups A and B, but not in group C, were found to shed turkey astrovirus in their feces, as detected by RT-PCR. These results provide a preliminary indication that TAstV-2 from PES birds may be more pathogenic than TAstV-2 from apparently healthy poults. Further studies are needed to determine if pathogenic and nonpathogenic strains of TAstV-2 exist in the environment. These results also reinforce our previous observations that astrovirus is involved in PES, causing significant retardation in growth and weight gain. PMID- 22080014 TI - The effect of including Lactobacillus reuteri KUB-AC5 during post-hatch feeding on the growth and ileum microbiota of broiler chickens. AB - The probiotic strain Lactobacillus reuteri KUB-AC5, which was originally isolated from chicken intestine, was fed to newborn broiler chicks for the first week post hatch. The growth and ileum microbiota of the chickens were carefully monitored for 6 wk. The inclusion of 5 log cfu/g of feed statistically increased the BW gain in the first week compared with that of the control group, but this effect did not continue thereafter. Significant effects on host feed consumption and the feed-to-growth conversion ratio were not detected. The total amount and composition of ileum bacteria were investigated by quantitative PCR and pyrosequencing of the 16S rRNA gene (rDNA), respectively, and were compared between the control and the probiotic-treated groups. The amount of total bacterial 16S rDNA in ileum samples at d 42 was 5 times higher in the probiotic group than in the control, whereas no significant difference was observed at d 21. A composition analysis revealed the establishment of lactobacilli-enriched microbiota in the probiotic-treated chickens at d 42. At this point, the population level and species diversity of lactobacilli were significantly enhanced compared with those of the control group. In addition, Actinobacteria, mainly genera Corynebacterium and Dietzia, were also statistically higher in the probiotic group. However, Proteobacteria, including those of the family Campylobacterales and some other nonbeneficial bacterial groups, were decreased in the probiotic group at the growing stage. Therefore, with probiotic supplementation, it was demonstrated that Lactobacillus reuteri KUB-AC5 in the early post-hatching period had a delayed effect on ileum microbiota, which resulted in the enrichment of potentially beneficial lactobacilli and the suppression of Proteobacteria, including nonbeneficial bacterial groups. PMID- 22080015 TI - Effects of increasing dietary concentrations of corn naturally contaminated with deoxynivalenol on broiler and turkey poult performance and response to lipopolysaccharide. AB - In this study, 2 experiments determined the effects of increasing dietary concentrations of deoxynivalenol (DON) on performance, intestinal morphology, and measures of innate immunity in broilers and turkeys. For experiment 1, the 3-wk study used 5 concentrations of DON (up to 18 or 10 mg of DON/kg of feed in broilers or turkeys, respectively) from naturally contaminated corn. The BW gains were cubically or quadratically affected by the increasing dietary concentrations of DON for broilers and turkeys, respectively; however, feed consumption was not affected. For experiment 2, the birds were subsequently injected or not injected with lipopolysaccharide (LPS) 24 h before tissue and blood sample collection. Dietary DON had no effect on intestinal crypt depth, but linearly increased the mid-ileal villus height in broilers (P = 0.04). An interaction was observed between the LPS challenge and the dietary DON with regards to heterophil to lymphocyte ratio (P < 0.05) in broilers, but not in turkeys. The cecal tonsil cell phagocytosis of microbeads was not affected by the dietary concentration of DON either with or without the subsequent LPS challenge for both broilers and turkeys. Conversely, the phagocytic capacity of cecal tonsil cells to engulf killed Staphylococcus aureus was significantly reduced (over 2.5-fold) when broilers were fed the highest concentration of dietary DON (non-LPS-challenged; P < 0.05). However, diets containing DON showed no effects on broilers when they were challenged with LPS. Antibody-dependent phagocytosis (S. aureus) was not affected in turkeys fed DON. Overall, corn naturally contaminated with up to 18 or 10 mg/kg of DON (broiler or turkey, respectively) reduced bird BW gain at 21 d of age, reduced antibody-dependent phagocytosis of previously killed S. aureus by cecal tonsil cells in non-LPS-challenged broilers, and greatly decreased heterophil to lymphocyte ratios in LPS-challenged broilers. PMID- 22080016 TI - Comparative metabolism of warfarin in rats and chickens. AB - Warfarin, a coumarin rodenticide, is commonly used worldwide for rodent control, and is often reported as the cause for poisoning accidents in nontarget animals, in particular bird species. However, the metabolism of warfarin in birds is still unclear. In a previous study, we found an unknown warfarin metabolite in chicken cytosolic fractions. In the present study, we aimed to clarify the cytosolic warfarin metabolites in chickens compared with those in rats. The cytosol fractions of both chicken and rat livers showed the metabolic activity of 2 diastereomers and 2 enantiomers of warfarin alcohol. In chicken cytosol, we found that the production level of (S)-warfarin-(S)-alcohol was markedly higher (32 fold) than that in rat cytosol. From the results of the inhibition assay, we finally suggest that aldehyde oxidase may mainly contribute to the warfarin alcohol products in chicken cytosol. PMID- 22080017 TI - A study of nutrient digestibility and growth performance of broiler chicks fed hairy and hairless canary seed (Phalaris canariensis L.) products. AB - A nutrient retention study and a growth study were conducted with broiler chickens to evaluate the nutritive value and potential toxicity of 2 hairless canary seed products-hulled seed and groats (cultivar CDC Maria), and one hairy hulled canary seed (cultivar Keet). Each treatment was replicated 6 times (6 groups of 4 birds each). The hairless canary seed groat, hairless hulled canary seed, and the hairy hulled canary seed contained 24.5, 21.8, and 16.3% CP; 7.1, 5.8, and 6.6% ether extract; 1.5, 14.2, and 12.3% acid detergent fiber, and 3,867, 3,205 and 3,292 kcal/kg of AME(n), on a DM basis, respectively. The hairless canary seed groat, hairless hulled canary seed, and the hairy hulled canary seed protein comprised, respectively, 0.49, 0.33, and 0.33% lysine (DM basis), which was 79, 78, and 67% digestible (apparent ileal); 0.65, 0.53, and 0.60% cysteine (DM basis), which was 86, 87, and 85% apparent ileal digestible; and 0.40, 0.30, and 0.25% methionine (DM basis), which was 89, 90, and 86% apparent ileal digestible. In the second study, a 35-d feeding study with male broiler chickens was conducted. The canary seed products were compared with a Canadian Western Red Spring wheat control. Each treatment was replicated 6 times (6 groups of 4 birds each). The test ingredients comprised 50% of the corn/soybean diets. The birds fed the hulled canary seed (hairy or hairless) had similar weight gain, feed intake, and G:F to those fed wheat. There were no statistically significant (P = 0.05) differences in the weights of the bursa, heart, kidneys, liver, spleen, or the pancreas, nor was there any effect on serum lactate dehydrogenase or creatine kinase. The data indicated that feeding hulled canary seed increased the number of gizzard ulcers (P < 0.01). It was concluded that canary seed does not contain anti-nutritional components that negatively affect broiler performance or bird health. However, the canary seed hulls may damage the gizzard lining. PMID- 22080018 TI - Early feeding and dietary lipids affect broiler tissue fatty acids, vitamin E status, and cyclooxygenase-2 protein expression upon lipopolysaccharide challenge. AB - Newly hatched chicks are often subjected to delayed access to feed and water because of shipment distances and hatchery practices, which may reduce growth and development of the immune system. The current study investigated the effects of early vs. late access to feed and dietary lipids (n-3 vs. n-6) on lipopolysaccharide (LPS)-induced alterations in tissue fatty acids, vitamin E status, and cyclooxygenase-2 (COX-2) protein expression. The chicks (n = 16/group) were fed a high or low n-3 diet within 5 to 5 h 30 min (early) or after 48 h (late) of hatching. Feeding high n-3 diets increased eicosapentaenoic acid (EPA, 20:5 n-3), docosapentaenoic acid (22:5 n-3), and docosahexaenoic acid (DHA, 22:6 n-3) in the liver, spleen, and plasma (P < 0.05). Feeding low n-3 diets increased arachidonic acid in the liver and plasma (P < 0.05). Early access to feed led to increases in liver oleic acid and reduction in arachidonic acid as compared with late-fed birds (P < 0.05). No effect of time of feeding on fatty acids in the spleen was observed. Early feeding led to significant increases in linoleic and arachidonic acids in the plasma (P < 0.05). Stearic acid was higher in the plasma of low n-3 early-fed as opposed to low n-3 late-fed birds (P < 0.05). The LPS challenge led to an increase in liver total fat content (P < 0.05). The total fat content in the spleen and plasma were not affected by LPS injection (P > 0.05). The LPS-injected birds had decreases in oleic acid in the liver and plasma as compared with saline-injected birds (P < 0.05). Stearic acid increased upon LPS injection in the spleen and plasma (P < 0.05). Liver vitamin E content was significantly higher in saline-injected birds from the early high n-3 group compared with all treatment groups, except for the late low n-3 saline injected birds (P < 0.05). Plasma vitamin E was highest in the early low n-3 LPS injected birds compared with all other treatment groups (P < 0.05). The COX2:actin ratio in the early high n-3 LPS-injected birds was higher than that of the saline-injected birds of the same treatment (P < 0.05). However, no difference in COX-2 expression was observed between LPS- or saline-injected fed early low n-3, late high n-3, or late low n-3 diets (P > 0.05). No effect of diet, time of feeding, or LPS challenge on plasma isoprostanes was observed (P > 0.05). These results suggest that dietary and management strategies directed at modulating tissue polyunsaturated fatty acid status may offer the promise of modulating lipid metabolism and COX-2 expression in commercial poultry. PMID- 22080019 TI - Effects of the main cereal and type of fat of the diet on productive performance and egg quality of brown-egg laying hens from 22 to 54 weeks of age. AB - The influence of the main cereal and type of supplemental fat in the diet on productive performance and egg quality of the eggs was studied in 756 brown-egg laying hens from 22 to 54 wk of age. The experiment was conducted as a completely randomized design with 9 treatments arranged factorially, with 3 cereals (dented corn, soft wheat, and barley) and 3 types of fat (soy oil, acidulated vegetable soapstocks, and lard). Each treatment was replicated 4 times (21 hens/replicate). All diets were formulated to have similar nutrient content, except for linoleic acid, which ranged from 0.8 to 3.4% depending on the combination of cereal and fat source used. This approach allows for the estimation of the minimum level of linoleic acid in the diets that maximizes egg weight. Productive performance and egg-quality traits were recorded every 28 d, and the BW of the hens was measured individually at the beginning and at the end of the experiment. No significant interactions between main factors were detected for any of the variables studied. Egg production, egg weight, and egg mass were not affected by dietary treatment. Body weight gain was higher (P < 0.05) for hens fed corn or wheat than for hens fed barley, and also higher for hens fed lard than for hens fed soy oil or acidulated vegetable soapstocks. Egg quality was not influenced by dietary treatment, except for yolk color, which was greater (P < 0.001) for hens fed corn than for hens fed wheat or barley, and greater for hens fed lard than for hens fed soy oil or acidulated vegetable soapstocks. We concluded that brown-egg laying hens do not need more than 1.0% of linoleic acid in their diet (1.16 g/hen per d) to maximize egg production and egg size. The 3 cereals and the 3 fat sources tested can replace each other in the diet provided that the linoleic acid requirements to maximize egg size are met. PMID- 22080020 TI - Effects of a phytogenic feed additive on growth performance and ileal nutrient digestibility in broiler chickens. AB - A study was undertaken to examine the effects of a phytogenic feed additive (PFA) containing essential oils of thyme and star anise as lead active components on the growth performance and apparent ileal nutrient digestibility in broiler chickens. In total, 528 one-day-old Cobb male broilers were randomly divided into 4 dietary treatment groups with 6 replicate pens per treatment group (22 birds each). The dietary treatments were a control starter and grower basal diet without PFA or 150, 750, or 1,500 mg/kg of PFA. Body weight, weight gain, and feed intake were not significantly influenced by the feed additive, but the feed conversion ratio during the grower (22-42 d) and overall (1-42 d) periods improved linearly (P < 0.05) by the administration of PFA compared with that of the control diet. The average weights of the liver, heart, kidneys, and spleen were not significantly affected by the PFA. The results of the apparent ileal digestibility of crude ash, CP, crude fat, calcium, and phosphorus showed a linear increase (P < 0.05) related to the increase of PFA dose in the diet. Therefore, the means of digestibility of these nutrients were significantly higher in birds fed the PFA for all categories of age compared with the digestibility of these nutrients in the controls. In conclusion, the mode of action of the tested PFA can be explained by an improvement in the nutrient digestibility in the small intestine. The underlying physiological mechanisms, however, need to be characterized further. PMID- 22080021 TI - Replacement of corn in the diet of broiler chickens using foxtail millet produced by 2 different cultivation strategies. AB - Foxtail millet is well-suited to climatic conditions in semi-arid tropic regions where it is cultivated using both agro-ecologic and conventional cultivation practices. This study evaluated the nutritional value, digestibility, and physiological effects of agro-ecologic and conventionally cultivated foxtail millet in comparison with corn. Chemical and TME(n) analysis of foxtail millet cultivated conventionally and agro-ecologically indicated similar nutritional value. In total, 432 eight-day-old Ross 308 broiler chicks, using a 2 * 3 factorial arrangement, were randomly assigned to 4 replicate pens for each of 6 isonitrogenous and isoenergetic diets. Experimental diets were formulated by replacing corn with conventional or agro-ecologic millet at 3 levels (33, 66, or 100% of corn replacement). Body weight at 21 and 42 d of age was higher (P < 0.05) at 100% millet inclusion versus the lower inclusion levels. At 42 d of age, feed intake and feed conversion ratios were also improved (P < 0.05) at the 100% millet inclusion level. Similarly, the apparent ileal digestibility of CP increased (P < 0.05) for 100% millet diets. There were no differences in ileal digestibility of nutrients between millet growth conditions. Millet inclusion level significantly affected small intestinal morphology such that crypt depth was lowest (P < 0.05) in the 100% inclusion group for duodenum, jejunum, and ileum at 28 d of age, and for duodenum and ileum at 42 d of age. The villus crypt ratio was also highest (P < 0.05) in the 100% millet inclusion group for jejunum and ileum at 28 d of age, and duodenum, jejunum, and ileum at 42 d of age. Millet growth condition did not markedly affect small intestinal morphology. Serum antibody responses to Gumboro and Newcastle diseases were not affected by millet inclusion level or growth condition. In conclusion, foxtail millet could be considered as an alternate cereal for inclusion in the diet of broiler chickens. Broiler chicken performance and physiological responses to foxtail millet were similar whether grown conventionally or using agro-ecologic practices. PMID- 22080022 TI - Multivariate evaluation of 1-dimensional sarcoplasmic protein profile patterns of turkey breast muscle during early post-hatch development. AB - Proteins are the main participants in metabolic pathways. However, the analysis of protein abundance patterns associated with those pathways is complicated by the large number of proteins involved. In this study, the objective was to present the application of principal component analysis (PCA) to permit the visualization of developmental proteomic patterns of sarcoplasmic proteins found in breast muscle. Different turkey genotypes and nutritional regimens were used to potentially increase the variability within the sarcoplasmic protein profile. Sarcoplasmic protein fractions from turkey breast muscle samples were collected at 6 ages between 7 to 24 d. Breast muscle samples were collected from 2 distinctly different turkey lines. The poults within each line were either ad libitum or restrict fed. Proteomic PCA plots showed a visual developmental pattern from 7 until 17 d. Multivariate ANOVA highlighted the effect of time point and feeding regimen among profile patterns. The use of different genotypes and feeding regimens influenced variability, which was measured by mean Euclidean distances and ellipses of the PCA plots. These treatment effects, however, did not mask the developmental patterns. After 17 d, the proteomic patterns converged, suggesting that a level of biological stability was achieved regardless of the genotype or treatment. The developmental pattern obtained by the PCA methodology can aid in the planning of more efficient experimental designs so the developmental stage of individuals can be more accurately assessed. PMID- 22080023 TI - Dietary effects of chelated zinc supplementation and lysine levels in ISA Brown laying hens on early and late performance, and egg quality. AB - It has been hypothesized that zinc (Zn) levels beyond those that are nutritionally required may favor the utilization of dietary lysine, and consequently reduce the level of its inclusion into the diet. Therefore, the possible effects of interaction between chelated Zn and the level of lysine (Lys) on egg production and egg quality of laying hens were evaluated. In total, 720 ISA Brown layer hens aged 24 to 36 wk (early phase) and 48 to 60 wk (late phase) were allotted in a completely randomized factorial design that used 3 Zn and 5 Lys levels (6 replications, 8 birds/replication). All birds aged 37 to 47 wk (between early and late phases) were fed a standard diet and maintained under the same experimental design. The Zn levels used were 137, 309, and 655 mg/kg; and the Lys levels were 0.560, 0.612, 0.677, 0.749, and 0.851%. The optimal levels of Lys digestibility were based on laboratory analyses with regard to the weighted average relationship between 83.5% digestibility and the total Lys from principal ingredients. There was no effect of interaction found between the dietary levels of Zn and Lys for most of the variables studied; however, each had an independent effect on the variables. An increase in Zn from 137 to 655 mg/kg had no significant effect (P > 0.05) on the performance of hens in both phases; however, it showed a significant effect on egg quality (P < 0.01), principally on mineral composition. Increased Zn resulted in decreased shell weight, percentage of ash, yolk ash deposition, and total ash deposition. On the other hand, an increase in Lys from 0.560 to 0.851% significantly affected (P < 0.002) several performance parameters and the chemical composition of the eggs, including feed intake, feed conversion efficiency, BW gain, egg weight, and production. In conclusion, there was no interaction found between Zn and Lys, but higher dietary levels of chelated Zn reduced bird performance and egg quality parameters, whereas higher Lys levels could be beneficial to bird performance and egg quality. PMID- 22080024 TI - Relationship among fluctuating asymmetry, morphological traits, and sperm quality in layers. AB - The aim of the present study was to analyze the relationship between fluctuating asymmetry and the mean value of several bilateral traits (toe, leg, wing, and wattle lengths, and leg width) and sperm quality variables (volume, appearance, concentration, motility, morphological abnormalities, and acrosome and membrane integrities) in different breeds of layers. In total, 165 roosters were sampled at 36 wk of age. There was no significant correlation between fluctuating asymmetry and sperm quality variables. There was a positive association (P < 0.01) between sperm motility and concentration, and between sperm concentration and volume. Sperm motility was positively correlated (P < 0.001) with morphologically normal sperm. The membrane integrity did not correlate with motility. This study shows different results for the association between sperm quality variables and morphological traits. There was a negative association (P < 0.05) between toe length and membrane integrity and between leg length and sperm motility. In disagreement with the expected results, wattle length did not correlate with any sperm quality parameter. In general, roosters with longer legs had longer toes and wings, whereas those with longer wattles had longer toes, legs, and wings. Breed effect was significant for the sperm motility index (P < 0.001), concentration and membrane integrity (P < 0.05), and morphologically normal sperm (P < 0.01). Spanish breeds had similar sperm quality variables to the White Leghorn population, although the Blue Andaluza (a Spanish breed) showed smaller values for sperm motility index and concentration and membrane integrity. Breed effect was not significant for any fluctuating asymmetry, with values ranging from 1 to 6% of the trait value; however, breed effect was significant for all of the morphological traits (P < 0.001). The CV was higher for ejaculate volume and concentration, intermediate for semen appearance, motilities, and morphologically normal sperm, and smaller for membrane and acrosome integrity. In conclusion, the results suggest that fluctuating asymmetry is of limited use for assessment of rooster sperm quality. Some morphological traits (toe length, leg length, and leg width) might be associated with some sperm quality variables (motility and membrane integrity). PMID- 22080025 TI - Influence of red light on reproductive performance, eggshell ultrastructure, and eye morphology in Thai-native hens. AB - In total, 120 Thai-native pullets (Gallus domesticus) aged 18 wk were housed in floor pens, located in a conventional open-sided shed under natural daylight (12L:12D) and randomly divided into 3 groups; Groups 1 (DF) and 2 (DR) were reared under natural daylight and supplemented with fluorescent or red light, respectively, whereas group 3 (R) was maintained in light-controlled pens and exposed only to red light. The red light was produced by light-emitting diodes. All treatments were provided with 16 h of light per day (16L:8D) during a 26-wk egg-laying period, and there were 4 replicate pens of 10 hens for each treatment. Photostimulation of these light sources was initiated at 18 wk of age and subsequent effects on reproductive performance were observed during the experimental period. Morphological characteristics of the eyes and eggshell microstructure were examined at the end of the study. Feed and water were provided ad libitum. There were no significant differences in BW, feed intake, egg weight, egg quality, or mortality rate due to the treatment. Pullets in the R and DR treatment groups commenced egg production significantly earlier than those in the DF treatment group. In early-season egg production (0-8 wk), cumulative egg number was significantly (P < 0.05) higher for the R treatment (25.9 eggs/hen) than for the DR (20.9) and DF (19.5) treatment groups. No significant differences in total egg production per hen occurred among the treatment groups. At 2 wk following photostimulation, hens in the R treatment group had significantly (P < 0.05) higher serum estradiol concentrations compared with hens in the other treatment groups. Neither eggshell structure nor eye morphology was affected by the treatments. It was concluded that the spectrum of red light did not affect live performance, egg production, egg quality, eggshell microstructure, or eye morphology of Thai-native hens, except for in accelerating sexual development. The light-emitting diode lighting system would be beneficial for energy savings and the reduction of rearing costs. PMID- 22080026 TI - Chicken feet bacteriological quality at 4 steps of technological processing. AB - The production of chicken feet is primarily intended for foreign markets, and there is still no specific legislation in Brazil that determines the quality standard of these products. The bacteriological quality of chicken feet was evaluated as a product for human consumption at different steps of the technological processes. Eighty broiler feet from 20 lots at 4 steps of processing were collected for quantitative analysis, total count of aerobic mesophilic bacteria, and determining the most probable number of coliforms and fecal coliforms. Thirty-eight pools of 15 broiler feet each from 19 lots were used for qualitative analysis and the isolation of Salmonella enterica spp. and Escherichia coli O157:H7. Escherichia coli O157:H7 was not found in any of the samples. Salmonella spp. were isolated in 68% (13/19) of the lots. The Salmonella Schwarzengrund serotype was found in 12 of the 13 lots of positive samples and the Salmonella Anatum and Salmonella Corvallis serotypes were identified in the remaining lot. Processing is effective in reducing contamination by mesophilic bacteria, coliforms, and Salmonella spp. in these products. This work constitutes the first study in Brazil on microbiological quality of chicken feet. PMID- 22080027 TI - Effect of alternative salt use on broiler breast meat yields, tenderness, flavor, and sodium concentration. AB - Fresh chicken breast fillets were marinated with gourmet-style salts: Himalayan pink salt, Sonoma gourmet salt, sel gus de Guerande, and Bolivian rose salt to evaluate their effects on marination and cook loss yields, tenderness, sensory attributes, and sodium concentration. Fresh chicken breast fillets (48-h postmortem) were vacuum tumbled (137 kPa at 20 rpm for 17 min) in a solution of water, salt, and sodium tripolyphosphate at a level of 20% of the meat weights. Instrumental analyses showed no significant difference (P > 0.05) in meat quality with respect to marination yield, cook yield, or shear-force value. There were also no significant differences (P > 0.05) in sensory descriptors between salt treatments. However, Sonoma gourmet salt showed a tendency (P = 0.0693) to score increased savory note values from panelists, whereas Bolivian rose salt received the lowest score. There were no significant differences (P > 0.05) in sodium concentrations between salt treatments, but numerically, sel gus de Guerande had the lowest sodium concentration, which could be important in producing reduced sodium products. Understanding different salts and sodium concentrations allows the poultry industry to use gourmet salts in products and maintain overall meat quality and flavor. PMID- 22080028 TI - Survival of artificially inoculated Escherichia coli and Salmonella Typhimurium on the surface of raw poultry products subjected to crust freezing. AB - Escherichia coli and Salmonella spp. are ubiquitous in the poultry production environment, and hence, their transmission to poultry products is of concern. Industry has widely used freezing as a strategy to halt pathogen growth, and more recently, crust freezing has been suggested as a means to improve mechanical operations, quality, and safety of poultry products. The purpose of this study was to evaluate the effect of crust freezing on the survival of Escherichia coli and Salmonella Typhimurium that were artificially inoculated on the surface of raw poultry products with or without adhering skin. Ampicillin-resistant (AR) E. coli JM 109 and nalidixic acid-resistant (NAR) Salmonella Typhimurium were used in the experiments. A set of cultures was subjected to cold-shock stress by storage at 4 degrees C for 10 d. After being either cold-shocked or non-cold shocked, commercial chicken breasts without skin and chicken thighs with skin were inoculated in separate experiments with each bacterium. Samples were crust frozen at -85 degrees C for 20 min or completely frozen at -85 degrees C for 60 min. The E. coli and Salmonella Typhimurium were recovered on appropriate selective and nonselective media containing the corresponding antibiotic. Log reductions and extent of injury were calculated and treatments were compared using ANOVA. No significant differences were observed in the reduction of cold shocked or non-cold-shocked bacteria on products with or without skin that were crust or completely frozen. The average reduction for E. coli was 0.15 log(10) cfu/mL of rinse, and for Salmonella Typhimurium 0.10 log(10) cfu/mL of rinse; therefore, none of the final reductions were greater than the desired target (1 log). Bacterial cell injury was not significantly different (P > 0.05) among any of the treatments. Data showed no practical significance for initial reduction of these pathogens from crust freezing and thus, this technology should not be considered as a strategy for the reduction of E. coli and Salmonella Typhimurium on poultry. PMID- 22080029 TI - Modeling the growth pattern of in-season and off-season Ross 308 broiler breeder flocks. AB - Growing the Ross broiler parent according to the target growth curve ensures that males and females achieve optimum lifetime performance and well-being. Accurate control of growth will lead to uniformity and sexual maturity, which are of crucial importance for the production of hygienic, healthy, and fertile eggs of high quality. This study examined the growth of Ross 308 broiler breeder flocks from hatch to 35 wk of age to identify which growth model would describe the growth of these animals most accurately. Growth was measured and modeled using linear and nonlinear functions, and the experimental growth curves were compared with target curves from the Parent Stock Management Manual for Ross 308 (Aviagen). Broiler breeder flock R6 (in-season from February until October) and flock R7 (off-season from August until April) were kept in an environmentally controlled breeder house from hatch until 35 wk of age. Three nonlinear growth functions (logistic, Gompertz, and Richards) and 3 polynomial functions (linear, second-order, and third-order) were applied. Parameters of the models were estimated by the least squares procedure. The fit of growth curves to experimental data was assessed using R(2). A t-test was used to identify significant differences in the goodness of fit of the model to the different data sets (breeder manual, R6, and R7). The third-order polynomial gave the best fit to the Ross 308 parent broiler BW data, with R(2) ranging from 0.992 to 0.998. Among the nonlinear growth functions, the Richards model gave the best fit to the data, with R(2) ranging from 0.992 to 0.995. The advantage of second- and higher order polynomial models is that they can be linearized and their parameters estimated by linear regression. PMID- 22080030 TI - A description of the growth of the major body components of 2 broiler chicken strains. AB - The objective of this work was to compare the growth and chemical composition of the main body parts of males and females of the Ross and Cobb broiler strains available in Brazil. In total, 1,920 chicks were raised in 16 floor pens, from which 4 birds of each strain and sex were sampled weekly for the required measurements. The strains and sexes were reared in separate pens, using 4 replications of 120 birds each. Four feeds, based on corn and soybeans, were used during the trial: feed 1 from 1 to 7 d, feed 2 from 8 to 28 d, feed 3 from 29 to 49 d, and feed 4 from 50 to 56 d of age (all of the birds were given the same feed for each time interval). All of the birds were weighed weekly and the 4 birds sampled from each strain and sex were weighed, fasted for 24 h, reweighed, killed, eviscerated, and dissected. The breast, drums, thighs, and wings were weighed, packed into identified plastic bags, and stored in a freezer to later be thawed and minced. They were then freeze-dried to obtain the water content, after which they were again milled before analyzing for protein, lipid, and ash using AOAC procedures. The Gompertz equation was fitted to the weights of the body parts as well as to the protein weights of the components. Using data from each individual chicken that was sampled, allometric regressions were fitted to the weights of the physical and chemical components, with ln body protein weight being the independent variable and ln component weight being the dependent variable. Although some of the allometric relationships between the various body parts and body protein weight differed statistically between strains and sexes, these differences were of little commercial significance, suggesting that the relative growth rates of the different body components of the genotypes tested in this trial have not been changed substantially by genetic selection. PMID- 22080031 TI - Use of neural network models to estimate early egg production in broiler breeder hens through dietary nutrient intake. AB - In this study, neural network (NN) models were constructed to predict early egg production in broiler breeder hens. By breaking down the early egg production data collected from 98 breeder houses into weekly intervals, 5 NN-based models were developed for 25 to 29 wk of age. Starting with 98 data lines for each week, the NN models were trained by 69 data lines and the remainder (n = 29) were considered as the testing set. The variables of interest for developing the models were ME (kcal/bird per day) and CP, TSAA, Lys, Ca, and available P (g/bird per day). The constructed models were subjected to an optimization algorithm. Therefore, the optimal values for the input variables to maximize early egg production in broiler breeder hens were obtained. Based on the considered criteria to evaluate the goodness of fit, the efficiency of NN-based models to estimate early egg production was confirmed. The optimization results revealed that the breeder hens consuming 407, 457, 470, 486, and 487 kcal of ME/bird per day showed the highest egg production during 25, 26, 27, 28, and 29 wk of age, respectively. Moreover, optimal performance of hens required the intake (g/bird per day) of the following during 25, 26, 27, 28, and 29 wk of age, respectively: CP: 20.3, 22.6, 25, 25.8, and 26; TSAA: 0.88, 1.02, 1.06, 1.07, and 1.07; Lys: 0.98, 1.0, 1.2, 1.3, and 1.32; Ca: 4.5, 4.6, 5.3, 5.0, and 5.4; and available P: 0.48, 0.55, 0.6, 0.61, and 0.62. Although the results showed that the energy and other nutrient requirements of broiler breeder hens during early egg production do not change in parallel with age, it seems that the company recommendations underestimated the nutrient requirements of hens during these weeks. PMID- 22080032 TI - Effects of maternal energy efficiency on broiler chicken growth, feed conversion, residual feed intake, and residual maintenance metabolizable energy requirements. AB - This study investigated the effect of maternal energy efficiency on broiler chicken growth and energy efficiency from 7 to 40 d of age. Residual feed intake (RFI) and residual maintenance ME requirement (RME) were used to measure energetic efficiency. Residual feed intake was defined as the difference between observed and predicted ME intake, and RME(m) as the difference between observed and predicted maintenance ME requirements. A total of 144 Ross-708 broiler breeder pullets were placed in individual laying cages at 16 wk of age. Hens with the greatest RFI (n = 32) and lowest RFI (n = 32) values from 20 to 56 wk of age were selected (maternal RFI; RFI(mat)). Selected hens were retrospectively assigned to a high- or low-RME(m) category (maternal RME(m); RME(mmat)). At 59 wk, eggs were collected for 8 d and pedigree hatched. A total of 338 broilers grouped by dam and sex were raised in 128 cages where feed intake, BW, and temperature were recorded from 7 to 40 d to calculate broiler feed conversion ratios, RFI, and RME(m). The design was a 2 * 2 * 2 factorial with 2 levels of RFI(mat), 2 levels of RME(mmat), and 2 sexes. Neither the RFI(mat) nor RME(mmat) category affected broiler offpring BW or total conversion ratio. The high RFI(mat) * low-RME(mmat) broilers had decreased growth to 40 d. Low-RFI(mat) * low-RME(mmat) broilers had a lower RME(m) (-5.93 kcal of ME/kg(0.60) per day) and RFI (-0.86 kcal of ME/d) than high-RFI(mat) * low-RME(mmat) broilers (RME(m) = 1.70 kcal of ME/kg(0.60) per day; RFI = 0.38 kcal of ME/d). Overall, hens with low maintenance requirements (low RME(m)) produced more efficient broilers when other efficiency related traits, represented in a lower RFI, were present. Exclusion of high-RFI * low-RME(m) hens from selection programs may improve energy efficiency at the broiler level. The RME(m) methodology is a viable alternative to evaluate energy efficiency in broilers because it avoids confounding environmental effects and allows measurement standardization. PMID- 22080033 TI - Comparison of the effect of different methods of molt: production and welfare evaluation. AB - The purpose of this study was to evaluate alternative molting protocols assessing hen welfare and performance during and after molt. Hyline W-36 pullets were housed at 15 wk of age, and their egg production was obtained during this first cycle. When birds were 80 wk, the following molting treatments were applied: a conventional molt consisting of 10 d of fasting followed by cracked corn for 8 d and a pullet developer diet for 10 d; and 4 alternative molting programs: a soy hulls-based diet (12% CP, 1,455 kcal/kg of ME, and 1.38% Ca) offered for 14 d followed by cracked corn for 4 d and a pullet developer diet for 10 d; and the other 3 molt regimens consisted of feeding soy hulls for 4, 8, or 12 d followed by 10, 6, or 2 d, respectively, of a soy hulls-based diet and 4 d of cracked corn plus 10 d of a pullet developer diet. A nonmolted group of birds was fed a laying hen diet during the experimental period. Hen-day egg number was recorded daily for 56 wk (through 80-136 wk of age). The nonmolted hens showed lower hen-day production and fewer intact eggs and a higher number of cracked and shell-less eggs compared with those of the molted hens (P < 0.0001). A significant treatment by age effect (P < 0.0001) was observed for the variables of high-density lipoproteins and triglycerides. Control hens showed the lowest high-density lipoprotein concentration and the highest triglyceride levels at 84 wk of age when compared with all treatments. The lack of difference in heterophil-to lymphocyte ratio during molt suggests little influence of molting protocols on this variable. Regardless of the treatments, molting was deleterious to bone quality. A high mobilization of Ca through bone resorption for eggshell formation could explain the results obtained. Behavioral patterns coincided with a decline in frustration activities and an increase in alertness as molt proceeded until 83 wk of age. Alternative molting diets consisting of soybean hulls were successful in providing acceptable postmolt egg production performance. PMID- 22080034 TI - Nanosilver effects on growth parameters in experimental aflatoxicosis in broiler chickens. AB - Aflatoxicosis is a cause of economic losses in broiler production. In this study, the effect of one commercial nanocompound, Nanocid (Nano Nasb Pars Co., Iran) was evaluated in reduction of aflatoxin effects on the growth and performance indices in broiler chickens suffering from experimental aflatoxicosis. For this, a total of 300 one-day-old broiler chicks (Ross strain) were randomly divided into 4 groups with 3 replicates of 15 chicks in each separated pen during the 28-day experiment. Treatment groups including group A: chickens fed basal diet, group B: chickens fed 3 ppm productive aflatoxin in basal diet, group C: chickens fed basal diet plus 2500 ppm Nanocid, and group D: chickens fed 3 ppm productive aflatoxin and 2500 ppm Nanocid, in basal diet. Data on body weight, body weight gain (BWG), feed intake, and feed conversion ratio (FCR) were recorded at weekly intervals. Also cumulative data were assessed. Results showed, although supplement of Nanocid to conventional diet had no effect on performance but addition of Nanocid to diet containing 3 ppm aflatoxin increased significantly the cumulative BWG, cumulative feed consumption and decreased FCR in the last 2 weeks of experimental period. The improvement in these performance indices by supplement of Nanocid to diet containing aflatoxin showed the ability of Nanocid to diminish the inhibitory effects of aflatoxin. PMID- 22080035 TI - The influence of the intensity of smoking and years of work in the metallurgy on pro-oxidant/antioxidant balance in the blood of smelters. AB - The aim of this study was to investigate the effect of cigarette smoking and occupational exposure to heavy metals on the degree of pro-oxidant/antioxidant imbalance in smelters. The investigations were performed on the blood and urine of 400 subjects: 300 male copper smelters and 100 nonexposed male subjects. Biological material was divided into three groups: nonsmokers, those who smoked less than 20 cigarettes a day and those who smoked more than 20 cigarettes a day. The results showed a significant increase in the concentration of lead, cadmium and arsenic in the blood and urine of smelters, while smoking more than 20 cigarettes a day caused a further increase in the concentration of these metals. The level of malondialdehyde was approximately twofold higher in the plasma of the smelters compared to the control group. We have observed a disturbance in the level of antioxidants in erythrocyte lysate manifested by an increase in metallothionein and glutathione concentrations as well as superoxide dismutase and glutathione peroxidase activities and the decrease in glutathione S transferase activity. Cigarette smoking, years of work in metallurgy and age of smelters were additional factors significantly affecting the pro oxidant/antioxidant balance. PMID- 22080036 TI - Effect of combined occupational exposure to noise and organic solvents on hearing. AB - Noise exposure has been commonly regarded as the main hazard of occupational hearing loss. Recent studies indicate that several chemicals, including organic solvents have ototoxic effects. This study aimed at evaluating the hearing of workers exposed to both noise and a mixture of organic solvents at concentrations anticipated as safe. The study comprised three groups. The first one included 70 workers exposed to noise only, the second group consisted of 93 workers exposed to organic solvents and noise, and the control group included 59 individuals exposed to neither noise nor organic solvents. The three groups were matched for age, socioeconomic status, and smoking habit. The results of this study revealed that there was no statistically significant difference between the two exposed groups as regards the duration of exposure. There was a highly statistically significant difference between the two exposed groups as regards the different types of hearing loss (conductive deafness, sensory neural hearing loss, and mixed type) compared with the control one. Our study reported that sensory neural hearing loss occurred earlier in subjects with combined exposure to noise and solvents at a mean duration of exposure (16.38 +/- 9.44 years) compared to (24.53 +/- 9.59 years) the subjects with sole exposure to noise. The difference between the two groups was statistically significant regarding this type of hearing impairment (p < 0.05). There was a positive significant correlation between hearing impairment and duration of exposure in the two exposed groups. As regards the results of the environmental monitoring, both noise exposure levels (dB) and levels of different organic solvents measured (mg/m(3)) in different work departments were less than the levels recommended by Egyptian Environmental Law No. 4 for 1994. It is recommended that in the case of combined exposure, noise and solvent levels should be lowered than the permissible limits recommended for either alone. PMID- 22080037 TI - Mercury induces the expression of cyclooxygenase-2 and inducible nitric oxide synthase. AB - Nuclear factor-kappaB (NF-kappaB) is a transcription factor that mediates the inducible expression of a variety of genes involved in immune and inflammatory responses. NF-kappaB activation induces numerous proinflammatory gene products including cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The divalent heavy metal mercury has been used for thousands of years. Although mercury is clearly toxic to most mammalian organ systems, especially the immune system, exposure has still increased in some areas of the world. However, the underlying toxic mechanism is not clearly identified. Here, we report biochemical evidence that mercury alone induces NF-kappaB activation, resulting in the induced expression of COX-2 and iNOS. The results suggest that mercury can induce inflammatory diseases by lowering host defense. PMID- 22080038 TI - Species identification of the Northern shrimp (Pandalus borealis) by polymerase chain reaction-restriction fragment length polymorphism and proteomic analysis. AB - Genomic and proteomic techniques for species identification of meat and seafood products are being widely used. In this study, a genomic approach was used to differentiate Pandalus borealis (the Northern shrimp), which belongs to the superfamily Pandaloidea, from 30 crustaceans consisting of 19 commercially relevant prawns/shrimps species that belong to the superfamily Penaeoidea, which include the families Penaeidae and Solenoceridae, and 11 other crustacean species, including prawns, shrimps, lobsters, and crabs. For this purpose, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was designed based on the amplification of the 16S rRNA/tRNA(Val)/12S rRNA mitochondrial regions using the primers 16S-CruF and 16S-CruR. The 966-bp PCR products were produced and cleaved with the restriction enzymes AluI, TaqI, and HinfI, which provided species-specific restriction patterns. In addition, a proteomic approach, based on matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) and electrospray ionization-ion trap (ESI-IT) mass spectrometry, was used to identify and characterize new P. borealis-specific peptides that could be useful as potential markers of this species in protein based detection methods. To our knowledge, this is the first time a molecular method has been successfully applied to identify a wide range of prawn and shrimp species, including P. borealis, for either whole individuals or processed products. However, validation of the methods proposed here is required by applying them to a larger sample of individuals from different populations and geographic origins in order to avoid mainly false-negative results. PMID- 22080039 TI - Selective determination of inosine in the presence of uric acid and hypoxanthine using modified electrode. AB - This article describes the selective determination of inosine (INO) in the presence of important physiological interferents, uric acid (UA) and hypoxanthine (HXN), by differential pulse voltammetry at physiological pH (7.2) using the electropolymerized film of 3-amino-5-mercapto-1,2,4-triazole (p-AMTa) modified glassy carbon (GC) electrode. The electropolymerization of AMTa was carried out by the potentiodynamic method in 0.1M H(2)SO(4). An atomic force microscopy image shows that the p-AMTa film contains a spherical-like structure. Bare GC electrode fails to resolve the voltammetric signal of INO in the presence of UA and HXN due to the surface fouling caused by the oxidized products of UA and HXN. However, p AMTa film modified GC electrode (p-AMTa electrode) not only separates the voltammetric signals of UA, HXN, and INO, with potential differences of 730 mV between UA and HXN and 310 mV between HXN and INO, but also shows enhanced oxidation current for them. The selective determination of INO in the presence of UA and HXN at physiological pH was achieved for the first time. Using the amperometric method, we achieved the lowest detection of 50 nM for INO. The practical application of the current modified electrode was demonstrated by determining the concentration of INO in human blood serum and urine samples. PMID- 22080040 TI - Development and application of an in vitro apoptin kinase assay. AB - Apoptin, a protein derived from chicken anemia virus (CAV), induces apoptosis selectively in human tumor cells as compared with normal cells. This activity depends on phosphorylation and relocation of apoptin to the nucleus of cancer cells. Here, we describe an in vitro kinase assay that allows the biochemical characterization of apoptin kinase activity in tumor cells. The kinase phosphorylates apoptin in a strictly ATP-dependent fashion and in a broad salt range. The kinase activity is present constitutively in both cytoplasm and nucleus of various human tumor cells. Q-column chromatography showed that both cytoplasmic and nuclear fractions have identical fractionation characteristics, suggesting that the same kinase is present in both cellular compartments. Kinase activity derived from positive Q-column fractions bound to amylose-maltose binding protein (MBP)-apoptin and could be eluted with ATP only in the presence of the cofactor Mg(2+). Apparently, unphosphorylated apoptin interacts with the kinase and is released only after phosphorylation has occurred, proving that our assay recognizes the genuine apoptin kinase. This is further corroborated by the finding that apoptin is phosphorylated in vitro at positions Thr108 and Thr107, in concert with earlier in vivo observations. Our assay excludes cyclin-dependent kinase 2 (CDK2) and protein kinase C beta (PKC-beta), previously nominated by two separate studies as being the genuine apoptin kinase. PMID- 22080041 TI - A thin-layer chromatography plate prepared from BODIPY-based receptor immobilized SiO2 nanoparticles as a portable chemosensor for Pb2+. AB - A new fluorescence receptor based on BODIPY-immobilized silica nanoparticles (BODIPY-SiO(2)) exhibits a high affinity and selectivity for Pb(2+) over competing metal ions in water. An overall emission change of ca. 100-fold at the emission maximum was observed for Pb(2+). The fluorescence receptor BODIPY-SiO(2) can remove 97% and 95% of the initial 100 ppb Pb(2+) from human blood and waste solution, respectively. Experiments show the fluorescence receptor BODIPY-SiO(2) can be a potentially useful and effective agent for the selective separation and rapid removal of Pb(2+)in vivo. We also prepared a portable chemosensor kit by coating a 4 MUm thick film of BODIPY-SiO(2) onto a glass substrate. We found that this BODIPY-SiO(2) film detects Pb(2+) ions at pH 7.4 with a sensitivity of 3.2 nM. Finally, we tested the effect of pH on BODIPY-SiO(2) with Pb(2+) ions between pH 3.0 and 11.0. The fluorescence changes of BODIPY-SiO(2) were almost constant between pH 3 and 11. The results imply that the BODIPY-SiO(2) film is applicable as a portable chemosensor for detection of Pb(2+) ions in the environmental field. PMID- 22080042 TI - Partial removal of brown adipose tissue enhances humoral immunity in warm acclimated Mongolian gerbils (Meriones unguiculatus). AB - Temperate rodent species experience marked seasonal fluctuations in environmental temperatures. High thermoregulatory demands during winter usually weaken immune function. Brown adipose tissue (BAT) plays a crucial role in adaptive thermoregulatory process. Thus, we proposed the hypothesis that BAT might participate in the regulation of seasonal changes in immune function. The present study examined the trade-off between thermoregulation and immune function and the potential role of BAT in regulating seasonal changes in immune function in Mongolian gerbils. Specifically, surgical removal of interscapular BAT (34% of total BAT) was performed in male gerbils, and subsequently acclimated to either warm (23 +/- 1 degrees C) or cold (4 +/- 1 degrees C) conditions. Gerbils were then challenged with innocuous antigens and the immune responses were measured. Resting metabolic rate (RMR) and nonshivering thermogenesis (NST) were increased under cold conditions. However, the cost of thermoregulation during cold acclimation did not suppress T-cell mediated immunity and humoral immunity or decrease spleen mass, thymus mass and white blood cells. Partial removal of BAT significantly enhanced humoral immunity in warm-acclimated, but not in cold acclimated gerbils. T-cell mediated immunity, white blood cells and immune organs were not affected by BAT removal under both warm and cold conditions. Collectively, our results imply that BAT has a suppressive effect on humoral immunity in warm-acclimated gerbils and differential effects of BAT on humoral immunity under different temperatures (e.g., summer and winter) might be benefit to their survival. PMID- 22080043 TI - The developmental stage of chicken embryos modulates the impact of in ovo olfactory stimulation on food preferences. AB - Like mammals, bird embryos are capable of chemosensory learning, but the ontogeny of their feeding preferences has not been examined. We tested if the timing of stimulation in chicken embryos modulates the impact of in ovo olfactory stimulation on later food preferences. We exposed chicken embryos to an olfactory stimulus for a 4-day period in the middle or toward the end of the incubation period. The chicks were tested for their preference between foods with and without the olfactory stimulus in 3-min choice tests and on a 24-h time scale. Regardless of the type of food (familiar or novel) or the duration of the test, the control chicks not exposed to the olfactory stimulus consistently showed significant preferences for non-odorized foods. Chicks that were exposed in ovo to the olfactory stimulus did not show a preference for odorized or non-odorized foods. Only those chicks that were exposed to the olfactory stimulus toward the end of the incubation period differed from the controls and incorporated a higher proportion of odorized food into their diets on a 24-h time scale. This result indicates that olfactory stimulation at the end of embryonic development has a stronger impact on later feeding preferences. Our findings contribute to the growing pool of recent data appreciating the impact of olfactory signals on behavior regulation in avian species. PMID- 22080044 TI - Isolation and purification of seven lignans from Magnolia sprengeri by high-speed counter-current chromatography. AB - Seven lignans including (-)-maglifloenone, futoenone, magnoline, cylohexadienone, fargesone C, fargesone A and fargesone B were isolated and purified from Magnolia sprengeri Pamp. using high-speed counter-current chromatography (HSCCC) with two step separation. In the first step, a stepwise elution mode with the two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (1:0.8:0.6:1.2, 1:0.8:0.8:1, v/v) was used and 15.6 mg of (-)-maglifloenone, 19.2 mg of futoenone, 10.8 mg of magnoline, 14.7 mg of cylohexadienone and 217 mg residues were obtained from 370 mg crude extract. In the second step, the residues were successfully separated by HSCCC with the solvent system composed of petroleum ether-ethyl acetate-methanol-water (1:0.8:1.2:0.6, v/v), yielding 33.2 mg of fargesone C, 47.5 mg of fargesone A and 17.7 mg of fargesone B. The purities of the separated compounds were all over 95% determined by HPLC. The chemical structures of these compounds were confirmed by (1)H NMR, (13)C NMR and ESI-MS. PMID- 22080045 TI - The relationship between Candida species charge density and chitosan activity evaluated by ion-exchange chromatography. AB - Chitosan, a natural biopolymer presents antifungal activity that seems to be dependent on the interaction of its cationic amino groups and yeast cell surface. In this work we used ion-exchange chromatography to assess the surface charge density of Candida species and subsequently to relate this with their sensitivity profile to chitosan. The ability of several strains from distinct Candida species to interact with strong anionic and cationic exchangers was tested and the yeasts charge surface was assessed by measuring the zeta potential. Our results showed that all the yeast cells tested presented no interaction with the cationic resin and a species-related pattern of interaction was observed with the anionic resin. Specifically, regarding the Q-Sepharose support, Candida glabrata showed the lower retention affinity, followed by Candida albicans, presenting Candida tropicalis an intermediate profile; Candida parapsilosis and Candida guilliermondii revealed a stronger ionic interaction. The yeasts retention synergy in the anionic resin corroborates with the zeta potential outcomes. The behavior observed fit with sensitivity patterns to chitosan as the most susceptible species to chitosan presented higher affinity to the anionic resin in contrast to the less sensitive ones (C. albicans and C. glabrata). This data confirms and reinforces that chitosan activity is probably mediated by an ionic reaction between its amino free groups and ionic charges at the cell surface. PMID- 22080046 TI - Hearts and minds. AB - The American Heart Association liberalised guidelines for carotid stenting (CAS) into average risk patients based on the following interpretations and assumptions; (i) CAS doubles the risk of procedural stroke; (ii) CEA doubles the risk of procedural myocardial infarction (MI); (iii) peri-operative MI significantly reduces long-term survival; (iv) poorer long-term survival is attributable to a greater proportion of CEA patients dying after their peri operative MI. (v) reduced survival in CEA patients suffering a peri-operative MI offsets any benefit conferred by the lower procedural stroke risk so that; (vi) CAS is considered equivalent to CEA and may even be safer in those considered high risk for procedural MI. However, this much publicised rationale is flawed by the simple fact that the poorer survival rates observed in CREST were not attributable to a greater proportion of CEA patients dying following their procedural MI. In fact, a relatively higher proportion of CAS patients suffering a peri-operative MI died during follow-up. This observation changes how the literature should be interpreted. The clinical reality is that up to 10% of patients will suffer a stroke within seven days of their index TIA and the benefits of intervening in the hyperacute period after onset of symptoms (ie offering greater stroke prevention) will far outweigh any potential consequences of peri-operative MI and reduced life expectancy. Peri-operative MI should inform, but not drive the current debate. More importantly, it should not deflect attention away from the most important management priority; the prevention of stroke. This is one situation where the heart should not rule the head! PMID- 22080047 TI - Distinct microhemodynamic efficacy of arteriogenesis and angiogenesis in critically ischemic skin flaps. AB - Angiogenesis and arteriogenesis are regenerative vascular mechanisms dedicated to cope with critical ischemia after the interruption of the anatomical axial blood supply. The aim of the present study was to visualize, quantify and monitor the orchestration of these mechanisms and their microhemodynamic efficacy. A murine skin flap model was used that allowed for repetitive investigation of identical vascular structures by intravital microscopy. In the conduit arterioles, diameter and relative length increased to 133 +/- 20% and 260 +/- 80% over 7 days, respectively (both P<0.01), which reduced vascular resistance in this segment to 82 +/- 35%. After 1 week, a peak in accumulation of activated leukocytes could be observed in the postcapillary venules (P<0.01) without relevant hemodynamic changes. Thereafter, the arteriolar remodeling was replaced by angiogenesis. Functional capillary density was increased to 141 +/- 10% (P<0.01) and capillary diameter to 123 +/- 6% (P<0.01) after 14 days. Both mechanisms of vascular regeneration were associated with increases in the capillary perfusion index, to 194 +/- 42% (P<0.05) after 7 days and 366 +/- 21% after 14 days (P>0.01). Immunohistochemical analysis revealed a correlation of arteriogenesis with eNOS upregulation and of angiogenesis with VEGF upregulation in the corresponding vessels. In conclusion, arteriogenesis was the initial regenerative mechanism leading to arteriolar remodeling, reduction in vascular resistance, and increase in capillary perfusion over the first 7 days. Thereafter, capillary perfusion was improved by angiogenesis in terms of an increase in functional capillary density. PMID- 22080048 TI - Noninvasive assessment of localized inflammatory responses. AB - Inflammatory diseases are associated with the accumulation of activated inflammatory cells, particularly polymorphonuclear neutrophils (PMNs), which release reactive oxygen species (ROS) to eradicate foreign bodies and microorganisms. To assess the location and extent of localized inflammatory responses, L-012, a highly sensitive chemiluminescent probe, was employed to noninvasively monitor the production of ROS. We found that L-012-associated chemiluminescence imaging can be used to identify and to quantify the extent of inflammatory responses. Furthermore, regardless of differences among animal models, there is a good linear relationship between chemiluminescence intensity and PMN numbers surrounding inflamed tissue. Depletion of PMNs substantially diminished L-012-associated chemiluminescence in vivo. Finally, L-012-associated chemiluminescence imaging was found to be a powerful tool for assessing implant mediated inflammatory responses by measuring chemiluminescence intensity at the implantation sites. These results support the use of L-012 for monitoring the kinetics of inflammatory responses in vivo via the detection and quantification of ROS production. PMID- 22080049 TI - Elevated labile Cu is associated with oxidative pathology in Alzheimer disease. AB - Oxidative stress is implicated in Alzheimer disease (AD) pathogenesis, for which evidence indicates that radical species are generated by the redox-active biometal Cu. The contribution of labile Cu to the oxidative stress observed in AD has not been evaluated. The Cu content of postmortem cortical tissue from nondemented elderly controls and AD cases was measured using inductively coupled plasma mass spectroscopy, and the proportion of labile Cu was assessed using the Cu-phenanthroline assay. Further, the capacity of the tissue to stabilize Cu(2+) was evaluated using immobilized metal-affinity chromatography, and the level of tissue oxidative damage was determined by the presence of thiobarbituric acid reactive compounds. We identified elevated levels of exchangeable Cu(2+), which were correlated with tissue oxidative damage; additionally, we noted an increased capacity of AD cortical tissue samples to bind Cu(2+). This deranged Cu homeostasis reflects the homeostatic breakdown of Cu observed in AD and supports biometal metabolism as a therapeutic target. PMID- 22080050 TI - Impact of a conservative red blood cell transfusion strategy in children undergoing hematopoietic stem cell transplantation. AB - A 2008 randomized trial of critically ill, but stable, children reported the safety of transfusing red blood cells at a hemoglobin threshold of 7 g/dL. In 2009, we adopted the same transfusion criteria in our hematopoietic stem cell transplantation patients. Regression modeling was used to compare data obtained during primary admission for hematopoietic stem cell transplantation in calendar years before and after our practice change. Sixty-six patients admitted in the preintervention year were compared with 75 postintervention. Pre- and postpatients were similar in diagnoses and type of transplantations. Postintervention, median hemoglobin pretransfusion significantly decreased from 8.8 g/dL to 6.8 g/dL (P < .0001). In addition, transfused red blood cell units received by patients dropped from 4 (interquartile range [IQR] 3, 8) to 3 (IQR, 2, 5), (P = .002), and number of transfusion days per patients decreased from 4 (IQR, 2,5) to 3 (IQR, 2, 5), (P = .01). There were no differences in length of stay, time to engraftment, or 100-day mortality. Median blood product charges per patient significantly decreased ($3,624 [IQR, $2,265, $6,040] to $2,185 [IQR, $1,812, $3,997], P = .004). Our initial experience suggests that implementation of a conservative transfusion strategy in otherwise stable children undergoing hematopoietic stem cell transplantation appears safe and lowers transfusion exposures. PMID- 22080052 TI - Conjugation of two complementary anti-cancer drugs confers molecular hydrogels as a co-delivery system. AB - We reported in this communication on the first example of a molecular hydrogel system based on two complementary anti-cancer drugs for chemotherapy. PMID- 22080051 TI - The effect of orally administered glycogen on anti-tumor activity and natural killer cell activity in mice. AB - Natural killer (NK) cells, innate immune effectors that mediate rapid responses to various antigens, play an important role in potentiating host defenses through the clearance of tumor cells and virally infected cells. By using enzymatically synthesized glycogen (ESG) with the same characteristics as natural glycogen, we examined whether orally administered glycogen enhances the innate defense of tumor-implanted mice and the cytotoxicity of NK cells. Oral administration of ESG led to the suppression of tumor proliferation and the prolongation of survival times of tumor-bearing mice. Splenic NK activities of BALB/c mice treated orally with ESG were significantly higher than those of water-treated mice, which were used as a negative control. In addition, intraduodenal injections of ESG gradually and markedly lowered splenic sympathetic nerve activity, which has an inverse correlation with NK activity. Furthermore, ESG activated Peyer's patch cells to induce the production of macrophage inflammatory protein-2 (MIP-2), interleukin-6 (IL-6), and immunoglobulin A (IgA) from these cells. These results demonstrated that orally administrated glycogen significantly enhanced the cytotoxicity of NK cells by acting on Peyer's patch cells and autonomic nerves, and eventually induced the potentiation of host defenses. We propose that glycogen functions not only as an energy source for life support but also as an oral adjuvant for immunopotentiation. PMID- 22080053 TI - Influence of the coordination mode in [Ni{RC(S)NP(S)(OiPr)2}2] for the formation of nickel-containing nanoparticles. AB - The complex [Ni{2-PyNHC(S)NP(S)(OiPr)(2)-1,5,7-N,N',S}(2)] ([NiL(I)(2)]) dissolved in tri-n-octylphosphine (TOP) is decomposed in hot hexadecylamine (HDA) to give TOP-capped Ni nanoparticles. The same procedure using [Ni{2 MeC(6)H(4)NHC(S)NP(S)(OiPr)(2)}(2)-1,3-N,S] ([NiL(II)(2)]) and [Ni{PhC(S)NP(S)(OiPr)(2)-1,5-S,S'}(2)] ([NiL(III)(2)]) leads to the formation of NiS nanoparticles with the rhombohedral and hexagonal structures, respectively. NiH(x) nanoparticles were also produced from a mixture of [NiL(I)(2)] and N(2)H(4). The obtained Ni nanoparticles can be used for the catalytic addition of Ph(2)S(2) to 1-, 2- and 3-hexynes. PMID- 22080054 TI - Human erythema and matrix metalloproteinase-1 mRNA induction, in vivo, share an action spectrum which suggests common chromophores. AB - Matrix metalloproteinase 1 (MMP-1) is widely regarded as a biomarker of photoageing. We tested the hypothesis that MMP-1 mRNA expression and erythema share a common action spectrum by comparing the effects of erythemally equivalent doses of UVB, UVA1 and solar simulated radiation (SSR) on acute MMP-1 mRNA expression in whole human skin in vivo. Our results show comparable MMP-1 expression with all three spectra, which supports our hypothesis. The sharing of an action spectrum implies common chromophores, one of which is likely to be DNA. We have previously shown that all spectra that we used readily induce cyclobutane thymine dimers (T<>T) in human epidermis in vivo but we lack quantitative data on damage to dermal DNA. This is important because we do not know if dermal MMP-1 induction occurs via direct damage to the dermis, or indirectly via damage to the epidermis. Our results show that UVB induces about 3 times more T<>T compared with erythemally equivalent doses of UVA1, which is similar to our published epidermal data. This supports previously published work that also implicates an unknown UVA1 chromophore for erythema and MMP-1 induction. However, the distribution of the dermal DNA damage varies considerably with spectrum. In the case of UVB it is primarily in the upper dermis, but with UVA1 it is evenly distributed. Thus, irrespective of chromophores, MMP-1 induction by direct dermal damage by both spectra is possible. The practical conclusions of our data are that the small (<5%) UVB content of solar UVR is likely to be the main cause of photoageing, at least in terms of MMP-1 expression. Furthermore, prevention of erythema by sunscreen use is likely to result in reduced MMP-1 expression. PMID- 22080055 TI - ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer. AB - In prostate cancer genomic rearrangements involving genes encoding ETS transcription factors are commonly present, with androgen-regulated transmembrane protease, serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogen homologue (ERG) gene fusion occurring in 40-70%. Studies on the predictive value of ERG rearrangement as detected by in-situ hybridization or polymerase chain reaction have resulted in varying outcomes. The objective of this study was to correlate immunohistochemical ERG protein expression with clinico-pathological parameters at radical prostatectomy specimens, and to determine its predictive value for postoperative disease recurrence and progression in a prostate cancer screening cohort. Since androgen receptor is downregulated by ERG in cell lines, we also compared the expression of respective proteins. We selected 481 participants from the European Randomized Study of Screening for Prostate Cancer treated by radical prostatectomy for prostate adenocarcinoma. A tissue microarray was constructed containing representative cores of all prostate cancer specimens as well as 22 xenografts and seven cell lines. Immunohistochemical expression of ERG and androgen receptor was correlated with prostate-specific antigen (PSA), Gleason sum, pT-stage, surgical margins, biochemical recurrence, local recurrence, overall death and disease-specific death. ERG expression was detected in 284 patients (65%). Expression occurred significantly more frequent in patients with PSA <=10 ng/ml (P=0.024). There was no significant association between ERG and Gleason sum, pT-stage or surgical margin status. PSA (P=0.011), Gleason sum (P=0.003), pT-stage (P=0.001) and surgical margin status (P<0.001) all had independent value for postoperative biochemical recurrence, while positive surgical margin (P=0.021) was the only independent predictor for local recurrence. ERG protein expression did not have prognostic value for the clinical end points in uni- and multivariate analyses. A positive correlation existed between ERG and androgen receptor expression in single tissue cores (P<0.001). In conclusion, immunohistochemical ERG expression has no predictive value for prostate cancer recurrence or progression after radical prostatectomy. Increasing ERG levels are associated with the upregulation of androgen receptor expression in clinical specimens. PMID- 22080056 TI - CD133 expression associated with poor prognosis in ovarian cancer. AB - As a putative marker for cancer stem cells in human malignant tumors, including ovarian cancer, CD133 expression may define a tumor-initiating subpopulation of cells and is associated with the clinical outcome of patients. However, at this time its clinical significance in ovarian cancer remains uncertain. The aim of this study was to clarify the clinical role of CD133 expression in human ovarian cancer. Immunohistochemical staining of CD133 expression was performed in 400 ovarian carcinoma samples using tissue microarray. The associations among CD133 expression and clinical factors (diagnosis, tumor grade, cancer stage, and clinical response to chemotherapy), overall survival and disease-free survival time were analyzed. CD133 expression was found in 31% of ovarian carcinoma samples. Fisher's exact test and one-way analysis of variance suggested that CD133 expression was associated with high-grade serous carcinoma (P=0.035), late stage disease (P<0.001), ascites level (P=0.010), and non-response to chemotherapy (P=0.023). CD133 expression was also associated with shorter overall survival time (P=0.007) and shorter disease-free survival time (P<0.001) by log rank test. Moreover, CD133 expression was an independent predictor of shorter disease-free survival time in an unconditional logistic regression analysis with multiple covariates (P=0.024). Our results thus show that CD133 expression is a predictor of poor clinical outcome for patients with ovarian cancer, supporting the proposed link between CD133 and cancer stem cells. PMID- 22080057 TI - Metaplastic breast carcinomas are enriched in markers of tumor-initiating cells and epithelial to mesenchymal transition. AB - Metaplastic breast carcinomas constitute a distinct aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition toward spindle, chondroid, or osseous cell types. During tumorigenesis, epithelial to mesenchymal transition promotes invasion and metastasis and has been linked to the presence of stem cells. We hypothesized that metaplastic carcinomas may express epithelial to mesenchymal transition markers and may be enriched in tumor-initiating cells specifically in the non-glandular metaplastic elements. In 27 primary metaplastic carcinomas of the breast we tested the expression of epithelial to mesenchymal transition inducers ZEB1 and E-cadherin and the presence of tumor-initiating cells by using aldehyde dehydrogenase-1 (ALDH-1) and CD44(+)/CD24(-/low) immunohistochemistry. Of the 27 metaplastic carcinomas, 20 (74%) had squamous and/or spindle areas and 7 (26%) had heterologous elements (6 chondroid and 1 osseous). ALDH-1-positive and CD44(+)/CD24(-/low)-expressing cells were detected in the non-glandular metaplastic components (Fisher's exact, P=0.0017). E-cadherin expression was reduced or absent (aberrant) in all metaplastic components whereas it was normal in the glandular areas. On the contrary, overexpression of ZEB1 was detected in 41% (11 of 27) of the non-glandular, metaplastic components, and in none of the glandular areas. The presence of tumor-initiating cells, aberrant E-cadherin, and ZEB1 upregulation was associated in over 90% of the spindle areas and heterologous elements (chi(2) test, P<0.05). We provide first in situ evidence that epithelial to mesenchymal transition inducers and tumor-initiating cells are present specifically in the non-glandular components of metaplastic carcinomas. PMID- 22080058 TI - Extrathoracic metastases of thymic origin: a review of 35 cases. AB - Thymic tumors are categorized as types A, AB, B1, B2, B3, and thymic carcinoma under the World Health Organization (WHO) classification. Thymomas are typically slow growing tumors that predominantly involve the surrounding structures through direct invasion, while thymic carcinomas tend to be more aggressive. A significant number of patients are asymptomatic and can present with metastases as the first presentation. The exact incidence of extrathoracic metastases from thymoma is not known. This study describes a series of 35 cases of histologically documented metastatic thymomas and thymic carcinomas at extrathoracic sites. These cases were classified according to the current World Health Organization (WHO) classification criteria, and we present their clinical data as well as discuss the differential diagnoses of these lesions. Our study shows that all types of thymic tumors, regardless of histologic type, can be associated with invasion and metastases to thoracic and extrathoracic sites. PMID- 22080059 TI - PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer. AB - With the exception of germ-line mutations in ovarian cancer susceptibility genes, genetic predictors for women destined for ovarian serous cancer cannot be identified in advance of malignancy. We recently showed that benign secretory cell outgrowths (SCOUTs) in the oviduct are increased in frequency with concurrent serous cancer and typically lack PAX2 expression (PAX2-null). The present study examined the relationship of PAX2-null SCOUTs to high-grade serous cancers by comparing oviducts from women with benign gynecologic conditions and high-grade serous cancers. PAX2-null SCOUTs were identified by immunostaining and computed as a function of location, frequency (F) per number of cross-sections examined, and age. Six hundred thirty-nine cross-sections from 35 serous cancers (364) and 35 controls (275) were examined. PAX2-null SCOUTs consisted of discrete linear stretches of altered epithelium ranging from cuboidal/columnar, to pseudostratified, the latter including ciliated differentiation. They were evenly distributed among proximal and fimbrial tubal sections. One hundred fourteen (F=0.31) and 45 (F=0.16) PAX2-null SCOUTs were identified in cases and controls, respectively. Mean individual case-specific frequencies for cases and controls were 0.39 and 0.14, respectively. SCOUT frequency increased significantly with age in both groups (P=0.01). However, when adjusted for age and the number of sections examined, the differences in frequency between cases and controls remained significant at P=0.006. This study supports a relationship between discrete PAX2 gene dysregulation in the oviduct and both increasing age and, more significantly, the presence of co-existing serous cancer. We propose a unique co variable in benign oviductal epithelium-the PAX2-null SCOUT-that reflects underlying dysregulation in genes linked to serous neoplasia. PMID- 22080060 TI - p16INK4a and p14ARF mRNA expression in Pap smears is age-related. AB - Expression of high-risk HPV oncogenes results in a strong overexpression of cellular protein p16(INK4a). Immunohistochemical staining for p16(INK4a) is widely used as diagnostic marker. However, p16(INK4a) upregulation was also described as a biomarker of age. Here we analyzed p16(INK4a) expression in cervical smears to investigate if patient age may influence p16(INK4a)-based cervical cancer diagnosis. p14(ARF) was analyzed as a related supportive biomarker. Cervical scrapes were taken and stored in RNAlater. Total RNA was extracted, and cDNA was analyzed for expression of p16(INK4a) and p14(ARF) relative to beta-actin, by real-time reverse transcriptase PCR SYBR-Green I assays. Patient-derived smears referred as HSIL (n=45) had 6.27-fold higher p16(INK4a) mRNA expression than smears of cytologically normal and HPV-negative persons (n=48). Expression of p14(ARF) was 4.87-fold higher. When women with normal diagnoses were stratified for age, a significantly enhanced p16(INK4a) (2.88-fold) and p14(ARF) (1.9-fold) expression was observed as a consequence of ageing. A significant age-dependent upregulation was also observed in older HSIL patients (2.54-fold). Our study revealed significantly enhanced expression of p16(INK4a)/p14(ARF) mRNA in cervical scrapes referred to as HSIL compared with normal women. An age-dependent bias has to be considered when quantifying these tumor suppressor genes, with respect to cervical cancer development. PMID- 22080061 TI - Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. AB - This study is focused on therapy-related myeloid neoplasms after the most promising frontline FCR (fludarabine, cyclophosphamide, and rituximab) therapy in previously untreated chronic lymphocytic leukemia patients. A total of 28 therapy related myeloid neoplasm patients were identified, including 19 patients from 3 well-controlled FCR frontline trials (n=426 patients), giving an estimated frequency of 4.5% (1.9-8.3%) in a follow-up period of 44 months (range 5-122 months). Clinically, therapy-related myeloid neoplasms could emerge directly from 'prolonged myelosuppression' after FCR (10 patients), or after achieving complete hematological recovery (n=18). The overall latency was 35 months (range 3-118 months), with the former group of 23 months and the latter 42 months (P<0.001). In all, 10 cases presented as therapy-related acute myeloid leukemia and 18 as therapy-related myelodysplastic syndromes. Abnormal cytogenetics was present in 26 of 27 (96%) patients, with frequent chromosomes 5 and 7 abnormalities. The median survival was 7 months after therapy-related myeloid neoplasms. Our results indicate that the risk of therapy-related myeloid neoplasms secondary to frontline FCR therapy may not be as high as previously reported after removing the confounding factor of previous cytotoxic exposure, but this risk increased with older age and likely growth factor co-administration. Therapy-related myeloid neoplasms after FCR therapy shares clinicopathological features with therapy-related myeloid neoplasms secondary to other alkylating agents, but has a shorter latency interval indicating possible synergetic effects of the nucleotide analog fludarabine. The fact that therapy-related myeloid neoplasms can directly emerge from 'prolonged myelosuppression' warrants a bone marrow examination to rule out therapy-related myeloid neoplasms in this clinical setting. PMID- 22080062 TI - Aldehyde dehydrogenase 1A1 expression in breast cancer is associated with stage, triple negativity, and outcome to neoadjuvant chemotherapy. AB - Studies have shown that ALDH1A1 expression in the breast is associated with worse clinical outcome. ALDH1A1 inactivates cyclophosphamide, which is an integral agent in breast cancer chemotherapy regimens. The purposes of this study were to verify these results, to correlate ALDH1A1 expression with clinical outcome in patients treated with cyclophosphamide as part of the chemotherapy (adjuvant or neoadjuvant), and to evaluate ALDH1A1 as a useful marker to predict the clinical outcome of breast cancer subsets. A total of 513 primary breast cancers were studied. Tissue microarrays of the studied cases were stained with ALDH1A1. Key clinicopathological information was obtained. Disease-free survival and overall survival were calculated. Patients with neoadjuvant therapy who had substantial residual cancer burden (RCB) were included in the study. Fisher's exact test and Kaplan-Meier methods were used for statistical analysis. ALDH1A1 was expressed in 53 (10%) patients, with a higher frequency in triple negative, followed by HER2+, and finally hormonal receptor+/HER2- (P<0.0001). Tumors with advanced stage, node positive, or larger tumor size were correlated with ALDH1A1 expression (P=0.006, P<0.0001, and P=0.05, respectively). ALDH1A1 expression was also correlated with worse disease-free survival (P<0.006) and overall survival (P<0.01) in patients who were treated with neoadjuvant chemotherapy. In all, 8 of 22 (36%) received neoadjuvant chemotherapy and died of disease-expressed ALDH1A1 (P=0.008). Similarly, 8 of 23 (35%) who received neoadjuvant chemotherapy and had tumor recurrence expressed this marker (P=0.002). The risk of recurrence was fivefold greater than negative ALDH1A1 tumors. The risk of recurrence became 11-fold greater when cyclophosphamide but not trastuzumab was part of the regimen. Our results are consistent with previous studies. Moreover, we found that ALDH1A1 could be a useful marker to predict worse clinical outcome after chemotherapy in the neoadjuvant setting with substantial RCB. However, a larger cohort is required to verify our results. PMID- 22080063 TI - From PTEN loss of expression to RICTOR role in smooth muscle differentiation: complex involvement of the mTOR pathway in leiomyosarcomas and pleomorphic sarcomas. AB - Over the past decade, comprehensive genomic studies demonstrated that leiomyosarcomas and most of the tumors previously labeled as 'malignant fibrous histiocytomas' share complex karyotypes and genomic profiles, and can be referred to as 'sarcomas with complex genomics'. We recently reported a series of 160 sarcomas with complex genomics such as leiomyosarcomas, myxofibrosarcomas, pleomorphic liposarcomas/rhabdomyosarcomas and undifferentiated pleomorphic sarcomas. These tumors present with a frequent loss of chromosome 10 region encompassing the tumor suppressor gene PTEN. In the present study, we assessed PTEN genomic level and protein expression in this large series of sarcomas with complex genomics, as well as activation of downstream pathways. PTEN partial genomic loss was observed in only 46% of tumors, especially in well differentiated leiomyosarcomas, whereas up to 68% of these tumors demonstrate a loss of protein expression on western blot analysis. Specific discrepancies in PTEN immunohistochemical results suggested bias in this latter technique. PTEN mutations were rare, with only 4 point mutations in the 65 samples studied. Subsequent activation of AKT and mTOR pathways was only observed in 2 out of 3 of PTEN-deleted tumors. On the other hand, RICTOR, a major component of the mTOR complex 2, was significantly overexpressed in well-differentiated leiomyosarcomas. These results, confirmed on tissue micro-array immunohistochemical analysis of 459 sarcomas, could suggest a link between RICTOR overexpression and leiomyosarcomas oncogenesis. As therapeutics directed against the mTOR pathway are assessed in sarcomas, RICTOR overexpression in sarcomas and its links to therapeutic response need to be assessed. PMID- 22080064 TI - Histopathological findings in 29 lymph node biopsies with increased IgG4 plasma cells. AB - IgG4-related sclerosing disease encompasses a family of disorders associated with increased numbers of IgG4 plasma cells and mass forming lesions in various tissues. Lymphadenopathy is a common finding, seen in up to 80% of cases. In the largest series of cases to date, we describe histologic, immunohistochemical, special stain and flow cytometric findings in 29 cases of enlarged lymph nodes with increased IgG4 plasma cells. Lymph node biopsies showed all resection specimens; no needle core biopsies of tissue were evaluated. Cases were considered to have increased numbers of IgG4 plasma cells using the histological criteria outlined by Cheuk and Chan (2010): IgG4 plasma cells >50 cells in a high power field and >40% of IgG-positive plasma cells positive for IgG4. Additionally, increased intrafollicular plasma cells were a common finding. The lymph nodes showed a variety of reactive histological features including follicular hyperplasia, progressive transformation of germinal centers, interfollicular expansions, variable degrees of fibrosis, increased histiocytes and occasionally an appearance similar to that of plasma cell Castleman disease. PMID- 22080066 TI - The boulder in the stream. PMID- 22080065 TI - Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma. AB - The aims of this study were to investigate the role of vascular invasion (blood and lymphatic), vessel density and the presence of tumour-associated macrophages as prognostic markers in 202 cutaneous melanoma patients. Sections of primary melanoma were stained with lymphatic-specific antibody D2-40 to assess lymphatic vessel invasion and density in intratumoural and peritumoural areas; an antibody against endothelial marker CD34 was used to determine blood vessel invasion and density, and an antibody against CD68 was used to determine macrophage counts. Immunohistochemically determined vascular invasion (combined blood and lymphatic) was compared with that determined using haematoxylin and eosin (H&E) staining. The use of immunohistochemistry increased detection of vascular invasion from 8 30% of patients, and histological exam of H&E-stained tissue was associated with a false positive rate of 64%. Lymphatic vessel invasion occurred at a much higher frequency than blood vessel invasion (27 and 4% of patients, respectively). Although immunohistochemically detected vessel invasion was significantly associated with histological markers of adverse prognosis, such as increased Breslow thickness, ulceration and mitotic rate (all P<0.001), no associations with relapse-free or overall survival were observed. High macrophage counts were significantly associated with markers of aggressive disease, such as Breslow thickness, ulceration and mitotic rate (P<0.001, P<0.001, P=0.005, respectively), and lymphatic vessel invasion and high microvessel density (P=0.002 and P=0.003, respectively). These results suggest that vascular invasion is more accurately detected using immunohistochemistry and occurs predominantly via lymphatic vessels. The association of vessel characteristics with histological characteristics of the primary melanoma provides evidence for their biological importance in melanoma, but that they were not associated with clinical outcome attests to the value of existing histological prognostic biomarkers. We note that a high macrophage count may be associated with neovascularisation and primary tumour growth, and may also promote invasion through lymphatic vessels. PMID- 22080067 TI - Enduring principles in a fast-changing world. PMID- 22080068 TI - Ottawa 1986: back to the future. PMID- 22080069 TI - It's the environment, stupid! Declining ecosystem health is THE threat to health in the 21st century. PMID- 22080070 TI - Some bitter-sweet reflections on the Ottawa Charter commemoration cake: a personal discourse from an Ottawa rocker. AB - The Ottawa Charter both gave health promotion a solid framework and health promoters an identity. Yet, health promotion has far from reached its potential in being internalized in public health politics. Advocacy for health is one of the core missions for health promotion and the 25-year celebration of the Ottawa Charter offers a free ride, instead of being a missed opportunity. WHO has not met the expectations in taking advantage of the momentum and outcomes from the long series of global health promotion conferences. The series represents a lifeline for health promotion. Concepts like healthy public policy, supportive environments, social determinants, health and human rights, whole of government, globalization and others have been elaborated and framed in a health promoting context. The downside is that the footprints have not been bold, in particular not internationally. An upside is the development of research and science, underscored by a rapid development of scientific journals, textbooks, academic institutions and posts. A question arising is whether practise and policy making are left behind, since implementation on a grand scale still is lacking? Further and future efforts must be devoted to explore the processes and art of policy making. There is a need for more narratives and more health promoters involving themselves in policy making and politics. Health promotion is as relevant for the twenty-first century as ever. The challenges and opportunities are evident; the increasing global burden of non-communicable diseases, ageing populations, harmful use of alcohol, social determinants and fair societies improved governance and more. Health promotion can add value and WHO can step up its engagement. PMID- 22080071 TI - Ottawa revisited: 'enable, mediate and advocate'. AB - The Ottawa Charter for Health Promotion represents a turning point in public health thinking. The key messages and approaches, such as 'enabling, mediating and advocating', of this historical paper have not lost their timeliness and they are still considered to be the lessons for those health policy-makers who are willing to move beyond the health sector and to push health higher on the political agenda. PMID- 22080073 TI - Enable, mediate, advocate. AB - The authors of the Ottawa Charter selected the words enable, mediate and advocate to describe the core activities in what was, in 1986, the new Public Health. This article considers these concepts and the values and ideas upon which they were based. We discuss their relevance in the current context within which health promotion is being conducted, and discuss the implications of changes in the health agenda, media and globalization for practice. We consider developments within health promotion since 1986: its central role in policy rhetoric, the increasing understanding of complexities and the interlinkage with many other societal processes. So the three core activities are reviewed: they still fit well with the main health promotion challenges, but should be refreshed by new ideas and values. As the role of health promotion in the political arena has grown we have become part of the policy establishment and that is a mixed blessing. Making way for community advocates is now our challenge. Enabling requires greater sensitivity to power relations involved and an understanding of the role of health literacy. Mediating keeps its central role as it bridges vital interests of parties. We conclude that these core concepts in the Ottawa Charter need no serious revision. There are, however, lessons from the last 25 years that point to ways to address present and future challenges with greater sensitivity and effectiveness. We invite the next generation to avoid canonizing this text: as is true of every heritage, the heirs must decide on its use. PMID- 22080072 TI - Toward a post-Charter health promotion. AB - The past 25 years have seen enormous shifts in the environmental, political, economic and social landscapes that condition people's abilities to be healthy. Climate change is now a reality. China, India, Brazil and other 'developing' countries are emerging as new axes of political and economic power. Global capitalism has become increasingly predatory and crisis ridden, a result of unregulated and irresponsible greed of unimaginable scale. The elite response has been the increased erosion of the health and other social protection policies of redistribution that characterized the first-world run-up to the Ottawa Charter. These new realities challenge health promoters in ways unforeseen a quarter century ago. It is imperative that local determinants of health, to which health promoters give their attention, be traced to broader, even global levels of determinants. Support for groups acting at these levels should become a fundamental practice tenet. So, too, should advocacy for the social state, in which progressive taxation and hefty social investment blunt the health inequalities created by unfettered markets. As environmental and economic insecurities and inequalities increase in many of the world's countries, so does the risk of xenophobia and conflict. The roots of racism are complex; but weeding them out becomes another health promotion practice of the new millennium. There are some hopeful signs of health promoting political change, much of it emanating now from countries in the global South; but the threat of a return to health behaviourism in the face of the new global pandemic of chronic disease is real and must be confronted. PMID- 22080074 TI - Health promotion, the Ottawa Charter and 'developing personal skills': a compact history of 25 years. AB - The challenge of understanding what has happened in the 25 years since the Ottawa Charter would be difficult enough if there had been no Charter. However, our task is to interpret to what extent the Charter has influenced the world of health promotion as it is today. The task here is to consider what has happened regarding one action component of the Charter, notably developing personal skills. In taking only one of the five components, we are deconstructing the holistic approach that was implied in the Ottawa Charter and it is somewhat strange to isolate this action area from the others, and perhaps outside the 'spirit' of the Charter. Nonetheless, the approach will be to interpret this area broadly while still being restrictive and not venturing into discussions of the other action areas except where the connection is so strong that to isolate personal skills from the other area would be unproductive. The Ottawa Charter brought to the table, for health promotion and education, a growing recognition that health was a broad concept in its own right. It made explicit that ties to disease approaches were highly related to health education and promotion, but that health promotion had to go well beyond a narrow interpretation of the field. It recognized that active participation by people, to directly affect their health and the broader determinants of it, was paramount. PMID- 22080075 TI - Securing 'supportive environments' for health in the face of ecosystem collapse: meeting the triple threat with a sociology of creative transformation. AB - In this paper, we reflect on and explore what remains to be done to make the concept of supportive environments--one of the Ottawa Charter's five core action areas--a reality in the context of growing uncertainty about the future and accelerated pace of change. We pay particular attention to the physical environment, while underscoring the inextricable links between physical and social environments, and particularly the need to link social and environmental justice. The paper begins with a brief orientation to three emerging threats to health equity, namely ecological degradation, climate change, and peak oil, and their connection to economic instability, food security, energy security and other key determinants of health. We then present three contrasting perspectives on the nature of social change and how change is catalyzed, arguing for an examination of the conditions under which cultural change on the scale required to realize the vision of 'supportive environments for all' might be catalyzed, and the contribution that health promotion as a field could play in this process. Drawing on sociological theory, and specifically practice theory and the work of Pierre Bourdieu, we advocate rethinking education for social change by attending more adequately to the social conditions of transformative learning and cultural change. We conclude with an explication of three key implications for health promotion practice: a more explicit alignment with those seeking to curtail environmental destruction and promote environmental justice, strengthening engagement with local or settings-focused 'communities of practice' (such as the Transition Town movement), and finding new ways to creatively 'engage emergence', a significant departure from the current dominant focus on 'risk management'. PMID- 22080076 TI - Health promotion and health systems: some unfinished business. AB - One of the five action domains in the Ottawa Charter was Reorienting Health Services. In this paper, we reflect on why progress in this domain has been somewhat lethargic, particularly compared with some of the other action domains, and why now it is important to renew our commitment to this domain. Reorienting health services has been largely overlooked and opportunities missed, although good exceptions do exist. The occasion of the 25th anniversary of the Ottawa Charter represents an important opportunity for health promotion to: (i) renew its active voice in current policy debate and action and (ii) enhance achievements made to date by improving our efforts to advocate, enable and mediate for the reorientation of health services and systems. We outline six steps to reactivate and invest more in this action domain so as to be in a better position to promote health equitably and sustainably in today's fast changing world. Though our experience is mainly based in the European context, we hope that our reflections will be of some value to countries outside of this region. PMID- 22080077 TI - Reclaiming the social in community movements: perspectives from the USA and Brazil/South America: 25 years after Ottawa. AB - Since the Ottawa Charter 25 years ago, community participation has been adopted worldwide by nation states and communities as a core health promotion strategy. Rising inequities since that time, however, have been largely unchecked in the Americas and globally, and have presented us with an acutely paradoxical time for community participation and action. On the one hand, transnational globalized markets and accompanying economic and environmental devastation have challenged the effectiveness of community action to create health. On the other hand, hopeful signs of local through national and international activism and of new mechanisms for community engagement continue to surface as meaningful and effective democratic acts. This article presents a dialogue on these issues between colleagues in the United States and Brazil, and considers the broader applicability to Latin America and worldwide. We begin by discussing how community participation and community organizing grew out of our respective histories. We consider the catalytic role of the Ottawa Charter in spurring a reorientation of health promotion and the genesis of healthy city and community initiatives, as well as other current community organizing strategies and the growth of participatory research/CBPR. We unpack the potential for co-optation of both community and social participation and end with recommendations for what we can do to maintain our integrity of belief in democratic social participation to promote improved health and health equity. PMID- 22080078 TI - Healthy public in all policies. AB - The introduction of the notion of 'Healthy Public Policy' in the Ottawa Charter is considered a relevant response to the emerging social-political context of the 1970s and 1980s. It also remains an important, yet volatile, argument for the consideration of policy impact on health. In our analysis, however, those that continued to argue for Healthy Public Policies and those who should develop them have remained naive about the profound political dimensions of this exercise. Applying insights from the political sciences, we argue that greater levels of connectedness and commitment across civil society, and governance integration between sectors and levels of politicking and action are required for the further success of health integrated policies. The role of communities and the key communicative drivers of the Ottawa Charter (enable, mediate and advocate) need to be strengthened in more astute strategies. PMID- 22080079 TI - Ottawa 25+--'All aboard the Dazzling Bandwagon'--developing personal skills: what remains for the future? AB - The remit of this paper is to identify what might be the future direction of one of the Ottawa Charter's five main action areas; developing personal skills (DPS). It is contested that this was never going to be an easy task. This opinion article argues that, while a watchful eye should be kept on evolving and innovative DPS strategy and programmes that Ottawa principles generally espouse, that type of activity is not representative of the current location and practice of many health practitioners--particularly clinically located health professionals. Targeting such professionals who, otherwise, might remain unaware of or unengaged with health promotion practice is the main reform required for future DPS activity. It is predicted that, where universal progress can be made, the potential for DPS development would be significant. PMID- 22080080 TI - Ottawa 25 years on: a more radical agenda for health equity is still required. AB - This article revisits our 1995 assessment of the international health promotion agenda. Then we concluded that a more radical agenda for change was required in which responses were both technically sound and infused with an appreciation of the imperative for a change in politics and power. We conclude that this message is even more relevant in 2011 in an era when the continuing rise of transnational corporations (TNCs) poses a major threat to achieving improved and more equitable health. We support and illustrate this claim through the example of food and agriculture TNCs where the combination of producer subsidies, global trade liberalization and strengthened property rights has given increasing power to the corporate food industry and undermined national food security in many countries. We argue that a Health in All Policies approach should be used to monitor and enforce TNC accountability for health. Part of this process should include the use of a form of health impact assessment and health equity impact assessment on their activities. Civil society groups such as the People's Health Movement have a central role to play in monitoring the impacts of TNCs. PMID- 22080081 TI - What remains for the future: strengthening community actions to become an integral part of health promotion practice. AB - To mark the 25th anniversary of the Ottawa Charter, this paper will discuss what remains to be achieved in strengthening community actions as an integral part of health promotion practice. To do this, the paper discusses four key elements for the future of health promotion programmes: (1) engage communities to share priorities; (2) build community capacity; (3) mechanisms for flexible and transparent funding; and (4) being creative in order to expand or replicate successful local initiatives. The paper uses a number of international case study examples of how these key elements can be achieved in health promotion programmes. A major challenge for the future is how health promotion agencies can develop and maintain the trust of communities, especially socially marginalized communities in society. The paper concludes by identifying a number of short and longer term challenges to achieve these goals and offers a way forward for a brighter future direction of health promotion practice. PMID- 22080082 TI - Health promotion in Canada: 25 years of unfulfilled promise. PMID- 22080083 TI - Healthy public policies: looking ahead. AB - Health has moved up on the political agendas of most governments around the globe. The interdependence of economic, environmental and social conditions and health is increasingly understood. In turn, the experiences in health promotion with building healthy public policies become more important. Future "health in all policies" efforts, however, need to consider changing political contexts. There is some scope to review the focus on GDP when measuring economic development, and how health promotion considers both the opportunities and responsibilities of industry as part of healthy public policies. PMID- 22080084 TI - Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation. AB - Oxidized phospholipids, such as the products of the oxidation of 1-palmitoyl-2 arachidonoyl-sn-glycero-3-phosphocholine by nonenzymatic radical attack, are known to be formed in a number of inflammatory diseases. Interest in the bioactivity and signaling functions of these compounds has increased enormously, with many studies using cultured immortalized and primary cells, tissues, and animals to understand their roles in disease pathology. Initially, oxidized phospholipids were viewed largely as culprits, in line with observations that they have proinflammatory effects, enhancing inflammatory cytokine production, cell adhesion and migration, proliferation, apoptosis, and necrosis, especially in vascular endothelial cells, macrophages, and smooth muscle cells. However, evidence has emerged that these compounds also have protective effects in some situations and cell types; a notable example is their ability to interfere with signaling by certain Toll-like receptors (TLRs) induced by microbial products that normally leads to inflammation. They also have protective effects via the stimulation of small GTPases and induce up-regulation of antioxidant enzymes and cytoskeletal rearrangements that improve endothelial barrier function. Oxidized phospholipids interact with several cellular receptors, including scavenger receptors, platelet-activating factor receptors, peroxisome proliferator activated receptors, and TLRs. The various and sometimes contradictory effects that have been observed for oxidized phospholipids depend on their concentration, their specific structure, and the cell type investigated. Nevertheless, the underlying molecular mechanisms by which oxidized phospholipids exert their effects in various pathologies are similar. Although our understanding of the actions and mechanisms of these mediators has advanced substantially, many questions do remain about their precise interactions with components of cell signaling pathways. PMID- 22080085 TI - NADPH oxidase-dependent oxidative stress in the failing heart: From pathogenic roles to therapeutic approach. AB - Heart failure (HF) occurs when the adaptation mechanisms of the heart fail to compensate for stress factors, such as pressure overload, myocardial infarction, inflammation, diabetes, and cardiotoxic drugs, with subsequent ventricular hypertrophy, fibrosis, myocardial dysfunction, and chamber dilatation. Oxidative stress, defined as an imbalance between reactive oxygen species (ROS) generation and the capacity of antioxidant defense systems, has been authenticated as a pivotal player in the cardiopathogenesis of the various HF subtypes. The family of NADPH oxidases has been investigated as a key enzymatic source of ROS in the pathogenesis of HF. In this review, we discuss the importance of NADPH oxidase dependent ROS generation in the various subtypes of HF and its implications. A better understanding of the pathogenic roles of NADPH oxidases in the failing heart is likely to provide novel therapeutic strategies for the prevention and treatment of HF. PMID- 22080086 TI - Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes. AB - Statins, the widely prescribed cholesterol-lowering drugs for the treatment of cardiovascular disease, cause adverse skeletal muscle side effects ranging from fatigue to fatal rhabdomyolysis. The purpose of this study was to determine the effects of simvastatin on mitochondrial respiration, oxidative stress, and cell death in differentiated primary human skeletal muscle cells (i.e., myotubes). Simvastatin induced a dose-dependent decrease in viability of proliferating and differentiating primary human muscle precursor cells, and a similar dose dependent effect was noted in differentiated myoblasts and myotubes. Additionally, there were decreases in myotube number and size following 48 h of simvastatin treatment (5 MUM). In permeabilized myotubes, maximal ADP-stimulated oxygen consumption, supported by palmitoylcarnitine+malate (PCM, complex I and II substrates) and glutamate+malate (GM, complex I substrates), was 32-37% lower (P<0.05) in simvastatin-treated (5 MUM) vs control myotubes, providing evidence of impaired respiration at complex I. Mitochondrial superoxide and hydrogen peroxide generation were significantly greater in the simvastatin-treated human skeletal myotube cultures compared to control. In addition, simvastatin markedly increased protein levels of Bax (proapoptotic, +53%) and Bcl-2 (antiapoptotic, +100%, P<0.05), mitochondrial PTP opening (+44%, P<0.05), and TUNEL-positive nuclei in human skeletal myotubes, demonstrating up-regulation of mitochondrial mediated myonuclear apoptotic mechanisms. These data demonstrate that simvastatin induces myotube atrophy and cell loss associated with impaired ADP-stimulated maximal mitochondrial respiratory capacity, mitochondrial oxidative stress, and apoptosis in primary human skeletal myotubes, suggesting that mitochondrial dysfunction may underlie human statin-induced myopathy. PMID- 22080089 TI - Molecular characterization of Staphylococcus aureus carrying the panton-valentine leucocidin genes in northern Spain. AB - OBJECTIVES: To study the prevalence of the Panton-Valentine leucocidin (PVL) gene in methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus obtained in Gipuzkoa, northeastern area of the Basque Country, north central Spain, and perform the molecular characterization of PVL-positive isolates. METHODS: Molecular studies comprised: PVL gene detection by PCR, staphylococcal chromosome cassette mec (SCCmec) typing, spa sequencing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and detection of the arginine catabolic mobile element (ACME). RESULTS: Between 1978 and 2006, only two (0.3%) of the 686 MRSA isolates studied were positive for the PVL gene. This percentage increased between 2007 and 2009, when the PVL gene was detected in 30 of the 679 MRSA (4.4%) and in nine of the 1227 MSSA (0.7%) isolates. The 41 PVL-positive isolates characterized had eight different sequence types (STs). Twenty-three MRSA PVL-positive isolates were ST8, spa type t008, seven of which were ACME positive, erythromycin-resistant and showed the PFGE pattern (90-100% similarity) of the USA300 clone. ST8 was also the most prevalent ST among the nine MSSA PVL-positive isolates. CONCLUSION: The current epidemiology of PVL-positive MRSA in our region more closely resembles that of the USA rather than that of other European countries, being USA300 or USA300-like isolates the most prevalent ones. PMID- 22080088 TI - Down-regulation of Homer1b/c attenuates glutamate-mediated excitotoxicity through endoplasmic reticulum and mitochondria pathways in rat cortical neurons. AB - Glutamate-mediated excitotoxicity is involved in many acute and chronic brain diseases. Homer proteins, a new member of the postsynaptic scaffolding proteins, regulate glutamatergic signaling and intracellular calcium mobilization in the central nervous system. Here we investigated the effects of down-regulating Homer1b/c, a constitutively expressed long form of Homer proteins, on glutamate excitotoxicity-induced neuronal injury. In our in vitro excitotoxic models, we demonstrated that glutamate insults led to a dose-dependent neuronal injury, which was mediated by the intracellular calcium-dependent reactive oxygen species (ROS) production. We found that down-regulation of Homer1b/c with specific small interfering RNA (siRNA) improved neuronal survival, inhibited intracellular ROS production, and reduced apoptotic cell death after neurotoxicity. Homer1b/c knockdown decreased the intracellular calcium overload through inhibition of the group I metabotropic glutamate receptor (mGluR)/inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca2+ release from the endoplasmic reticulum (ER) in injured neurons. In addition, Homer1b/c siRNA transfection attenuated the activation of eukaryotic initiation factor 2alpha (eIF2alpha), RNA-dependent protein kinase-like ER kinase (PERK) and caspase-12, and inhibited the up regulation of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) after glutamate treatment. Homer1b/c knockdown also preserved the mitochondrial membrane potential (MMP), reduced cytochrome c (Cyt. c) release, and partly blocked the increase of capase-9 activity and Bax/Bcl-2 ratio. Taken together, these results suggest that down-regulation of Homer1b/c protects cortical neurons against glutamate-induced excitatory damage, and this neuroprotection may be dependent at least in part on the inhibition of calcium dependent ROS production and the preservation of the ER and mitochondrial function. PMID- 22080090 TI - Genotoxic and cytotoxic evaluation of the herbicide flurochloridone on Chinese hamster ovary (CHO-K1) cells. AB - The in vitro effects of flurochloridone (FLC) and its formulations Twin Gold Pack(r) (25% a.i.) and Rainbow(r) (25% a.i.) were evaluated on Chinese hamster ovary (CHO-K1) cells by genotoxicity [sister chromatid exchange (SCE)] and cytotoxicity [cell-cycle progression, proliferative rate index (PRI), mitotic index (MI), MTT, and neutral red] end points. Cells were treated for 24h within the 0.25-15MUg/ml concentration range. FLC and Twin Pack Gold(r) induced a significant and equivalent increase in SCEs regardless of the concentration. Rainbow(r)-induced SCEs at concentrations higher than 2.5MUg/ml; however, the increases were always lower than those induced by FLC and Twin Pack Gold(r). For all compounds, the PRI decreased as a function of the concentration titrated into cultures. Whereas only the highest FLC and Twin Pack Gold(r) concentrations induced a significant reduction of the MI, all tested Rainbow(r) concentrations induced MI inhibition. Overall, the results demonstrated that although all compounds were not able to reduce the lysosomal activity, the mitochondrial activity was diminished when the highest concentrations were employed. These observations represent the first study analyzing the genotoxic and cytotoxic effects exerted by FLC and two formulated products on mammalian cells in vitro, at least on CHO-K1 cells. PMID- 22080087 TI - The redox stress hypothesis of aging. AB - The main objective of this review is to examine the role of endogenous reactive oxygen/nitrogen species (ROS) in the aging process. Until relatively recently, ROS were considered to be potentially toxic by-products of aerobic metabolism, which, if not eliminated, may inflict structural damage on various macromolecules. Accrual of such damage over time was postulated to be responsible for the physiological deterioration in the postreproductive phase of life and eventually the death of the organism. This "structural damage-based oxidative stress" hypothesis has received support from the age-associated increases in the rate of ROS production and the steady-state amounts of oxidized macromolecules; however, there are increasing indications that structural damage alone is insufficient to satisfactorily explain the age-associated functional losses. The level of oxidative damage accrued during aging often does not match the magnitude of functional losses. Although experimental augmentation of antioxidant defenses tends to enhance resistance to induced oxidative stress, such manipulations are generally ineffective in the extension of life span of long-lived strains of animals. More recently, in a major conceptual shift, ROS have been found to be physiologically vital for signal transduction, gene regulation, and redox regulation, among others, implying that their complete elimination would be harmful. An alternative notion, advocated here, termed the "redox stress hypothesis," proposes that aging-associated functional losses are primarily caused by a progressive pro-oxidizing shift in the redox state of the cells, which leads to the overoxidation of redox-sensitive protein thiols and the consequent disruption of the redox-regulated signaling mechanisms. PMID- 22080091 TI - Development of a high-resolution Si-PM-based gamma camera system. AB - A silicon photomultiplier (Si-PM) is a promising photodetector for PET, especially for PET/MRI combined systems, due to its high gain, small size, and lower sensitivity to static magnetic fields. However, these properties are also promising for gamma camera systems for single-photon imaging. We developed an ultra-high-resolution Si-PM-based compact gamma camera system for small animals. Y(2)SiO(5):Ce (YSO) was selected as scintillators because of its high light output and no natural radioactivity. The gamma camera consists of 0.6 mm * 0.6 mm * 6 mm YSO pixels combined with a 0.1 mm thick reflector to form a 17 * 17 matrix that was optically coupled to a Si-PM array (Hamamatsu multi-pixel photon counter S11064-050P) with a 2 mm thick light guide. The YSO block size was 12 mm * 12 mm. The YSO gamma camera was encased in a 5 mm thick gamma shield, and a parallel hole collimator was mounted in front of the camera (0.5 mm hole, 0.7 mm separation, 5 mm thick). The two-dimensional distribution for the Co-57 gamma photons (122 keV) was almost resolved. The energy resolution was 24.4% full-width at half-maximum (FWHM) for the Co-57 gamma photons. The spatial resolution at 1.5 mm from the collimator surface was 1.25 mm FWHM measured using a 1 mm diameter Co 57 point source. Phantom and small animal images were successfully obtained. We conclude that a Si-PM-based gamma camera is promising for molecular imaging research. PMID- 22080092 TI - Time course of the recovery of three-dimensional eye position in patients with acute cerebellitis. AB - Listing's plane is a construction derived from eye position and reflects gravitational orientation. The cerebellum plays a key role in orienting and integrating sensory input concerning gravity from visual, vestibular and proprioceptive apparatuses. This suggests that the thickness of Listing's plane could serve as a novel parameter for evaluating the accuracy of the constructed gravity-oriented internal model. We report a case with acute cerebellitis along with data on Listing's plane, calculated from consecutive infrared video oculogram recordings. We found thickening of Listing's plane at the early stage of the disease, and a gradual reduction of the thickness into normal range in parallel with the recovery of the patient's posture and gate. Notably, clinical improvement of the patient's posture was delayed relative to the normalization of the thickness of Listing's plane. The thickness of Listing's plane reflects the stability of the cerebellar-mediated cognitive gravitational reference frame. This thickness value could serve as a parameter to quantitatively evaluate the function of the constructed internal model. Recovery from cerebellar ataxia (manifested as normalization of the thickness of Listing's plane) was followed by recovery of muscular strength lost during the period the patient was by his disease forced to assume a lying position. PMID- 22080093 TI - Genome size and base composition variation in natural and experimental Narcissus (Amaryllidaceae) hybrids. AB - BACKGROUND AND AIMS: Although there is evidence that both allopolyploid and homoploid hybridization lead to rapid genomic changes, much less is known about hybrids from parents with different basic numbers without further chromosome doubling. Two natural hybrids, Narcissus * alentejanus (2n = 19) and N. * perezlarae (2n = 29), originated by one progenitor (N. cavanillesii, 2n = 28) and two others (N. serotinus, 2n = 10 and N. miniatus, 2n = 30, respectively) allow us to study how DNA content and composition varies in such hybrids. METHODS: Flow cytometry measurements with two staining techniques, PI and DAPI, were used to estimate 2C values and base composition (AT/GC ratio) in 390 samples from 54 wild populations of the two natural hybrids and their parental species. In addition, 20 synthetic F(1) hybrid individuals were also studied for comparison. KEY RESULTS: Natural hybrids presented 2C values intermediate between those found in their parental species, although intra-population variance was very high in both hybrids, particularly for PI. Genome size estimated from DAPI was higher in synthetic hybrids than in hybrids from natural populations. In addition, differences for PI 2C values were detected between synthetic reciprocal crosses, attributable to maternal effects, as well as between natural hybrids and those synthetic F(1) hybrids in which N. cavanillesii acted as a mother. CONCLUSIONS: Our results suggest that natural hybrid populations are composed of a mixture of markedly different hybrid genotypes produced either by structural chromosome changes, consistent with classic cytogenetic studies in Narcissus, or by transposon-mediated events. PMID- 22080094 TI - Identification of H5N1-specific T-cell responses in a high-risk cohort in vietnam indicates the existence of potential asymptomatic infections. AB - BACKGROUND: Most reported human H5N1 viral infections have been severe and were detected after hospital admission. A case ascertainment bias may therefore exist, with mild cases or asymptomatic infections going undetected. We sought evidence of mild or asymptomatic H5N1 infection by examining H5N1-specific T-cell and antibody responses in a high-risk cohort in Vietnam. METHODS: Peripheral blood mononuclear cells were tested using interferon-gamma enzyme-linked immunospot T assays measuring the response to peptides of influenza H5, H3, and H1 hemagglutinin (HA), N1 and N2 neuraminidase, and the internal proteins of H3N2. Horse erythrocyte hemagglutination inhibition assay was performed to detect antibodies against H5N1. RESULTS: Twenty-four of 747 individuals demonstrated H5 specific T-cell responses but little or no cross-reactivity with H3 or H1 HA peptides. H5N1 peptide-specific T-cell lines that did not cross-react with H1 or H3 influenza virus HA peptides were generated. Four individuals also had antibodies against H5N1. CONCLUSIONS: This is the first report of ex vivo H5 HA specific T-cell responses in a healthy but H5N1-exposed population. Our results indicate that the presence of H5N1-specific T cells could be an additional diagnostic tool for asymptomatic H5N1 infection. PMID- 22080095 TI - Mannose-binding lectin contributes to deleterious inflammatory response in pandemic H1N1 and avian H9N2 infection. AB - BACKGROUND: Mannose-binding lectin (MBL) is a pattern-recognition molecule, which functions as a first line of host defense. Pandemic H1N1 (pdmH1N1) influenza A virus caused massive infection in 2009 and currently circulates worldwide. Avian influenza A H9N2 (H9N2/G1) virus has infected humans and has the potential to be the next pandemic virus. Antiviral function and immunomodulatory role of MBL in pdmH1N1 and H9N2/G1 virus infection have not been investigated. METHODS: In this study, MBL wild-type (WT) and MBL knockout (KO) murine models were used to examine the role of MBL in pdmH1N1 and H9N2/G1 virus infection. RESULTS: Our study demonstrated that in vitro, MBL binds to pdmH1N1 and H9N2/G1 viruses, likely via the carbohydrate recognition domain of MBL. Wild-type mice developed more severe disease, as evidenced by a greater weight loss than MBL KO mice during influenza virus infection. Furthermore, MBL WT mice had enhanced production of proinflammatory cytokines and chemokines compared with MBL KO mice, suggesting that MBL could upregulate inflammatory responses that may potentially worsen pdmH1N1 and H9N2/G1 virus infections. CONCLUSIONS: Our study provided the first in vivo evidence that MBL may be a risk factor during pdmH1N1 and H9N2/G1 infection by upregulating proinflammatory response. PMID- 22080096 TI - Intrinsic and environmental mutagenesis drive diversification and persistence of Pseudomonas aeruginosa in chronic lung infections. AB - Pseudomonas aeruginosa is a versatile opportunistic pathogen causing a wide variety of hospital-acquired acute infections in immunocompromised patients as well as chronic respiratory infections in patients suffering from cystic fibrosis or other chronic respiratory diseases. Several traits contribute to its ability to colonize and persist in the lungs of chronically infected patients, including development of high resistance to antimicrobials and hypermutability, biofilm growth, and alginate hyperproduction, or a customized pathogenicity, which may include the loss of classical virulence factors and metabolic changes. Here we argue that a combination of both intrinsic and environmental mutagenesis leads to a high number of mutant variants in the population. The conducive environment then triggers a positive feedback loop leading to adaptation and persistence of P. aeruginosa, rendering these chronic infections almost impossible to eradicate. PMID- 22080097 TI - T-cell immune responses and asymptomatic H5N1 influenza infection. PMID- 22080098 TI - Portomesenteric venous gas and pneumatosis cystoides intestinalis in systemic sclerosis. PMID- 22080099 TI - Management of febrile neutropenia in an acute oncology service. AB - BACKGROUND: Neutropenic fever in patients receiving chemotherapy is a medical emergency and should be treated promptly within 1 h with antibiotics as specified within the 2009 NCAG report on chemotherapy services. AIM: To determine door-to assessment, door-to-treatment and door-to-investigation intervals for patients with febrile neutropenia who presented to the inpatient Oncology Ward, the outpatient Oncology Day Unit and the Emergency Department in Addenbrooke's Hospital, Cambridge. DESIGN: Retrospective observational audit. METHODS: Thirty two patients on treatment for solid cancers who were admitted with febrile neutropenia between January and December 2010 were identified, and paper and electronic medical records were analysed to determine door to: assessment, treatment and investigation intervals. RESULTS AND CONCLUSIONS: Patients in this series were assessed quicker and received the first dose of antibiotics faster when they presented to an oncology ward rather than the emergency department. However, imaging was performed faster and blood results issued quicker if performed in the emergency department due to a better infrastructure that has been tailored to comply with national targets. Nonetheless, compliance with optimum standards of care was poor, with only 9% of sampled patients getting antibiotics within 1 h of presenting to hospital, and 53% within 1 h of being assessed by a clinician. PMID- 22080100 TI - Right thoracic stomach mimicking pleural empyema in an elderly man. PMID- 22080101 TI - Radiofrequency ablation of cardiac arrhythmias: past, present and future. AB - The treatment of cardiac arrhythmias has been revolutionized by the ability to definitively treat many patients with radiofrequency catheter ablation, rather than requiring lifelong medication. This review covers the history of how this has developed and the methods used currently and explores what the future holds for this rapidly evolving branch of Cardiology. PMID- 22080102 TI - Current and selectivity in a model sodium channel under physiological conditions: Dynamic Monte Carlo simulations. AB - A reduced model of a sodium channel is analyzed using Dynamic Monte Carlo simulations. These include the first simulations of ionic current under approximately physiological ionic conditions through a model sodium channel and an analysis of how mutations of the sodium channel's DEKA selectivity filter motif transform the channel from being Na(+) selective to being Ca(2+) selective. Even though the model of the pore, amino acids, and permeant ions is simplified, the model reproduces the fundamental properties of a sodium channel (e.g., 10 to 1 Na(+) over K(+) selectivity, Ca(2+) exclusion, and Ca(2+) selectivity after several point mutations). In this model pore, ions move through the pore one at a time by simple diffusion and Na(+) versus K(+) selectivity is due to both the larger K(+) not fitting well into the selectivity filter that contains amino acid terminal groups and K(+) moving more slowly (compared to Na(+)) when it is in the selectivity filter. PMID- 22080103 TI - The transcriptional coactivators, PGC-1alpha and beta, cooperate to maintain cardiac mitochondrial function during the early stages of insulin resistance. AB - We previously demonstrated a cardiac mitochondrial biogenic response in insulin resistant mice that requires the nuclear receptor transcription factor PPARalpha. We hypothesized that the PPARalpha coactivator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) is necessary for mitochondrial biogenesis in insulin resistant hearts and that this response was adaptive. Mitochondrial phenotype was assessed in insulin resistant mouse models in wild type (WT) versus PGC-1alpha deficient (PGC-1alpha(-/-)) backgrounds. Both high fat-fed (HFD) WT and 6 week-old Ob/Ob animals exhibited a significant increase in myocardial mitochondrial volume density compared to standard chow fed or WT controls. In contrast, HFD PGC-1alpha(-/-) and Ob/Ob-PGC-1alpha(-/-) hearts lacked a mitochondrial biogenic response. PGC-1alpha gene expression was increased in 6 week-old Ob/Ob animals, followed by a decline in 8 week-old Ob/Ob animals with more severe glucose intolerance. Mitochondrial respiratory function was increased in 6 week-old Ob/Ob animals, but not in Ob/Ob-PGC-1alpha(-/-) mice and not in 8 week-old Ob/Ob animals, suggesting a loss of the early adaptive response, consistent with the loss of PGC-1alpha upregulation. Animals that were deficient for PGC-1alpha and heterozygous for the related coactivator PGC-1beta (PGC-1alpha(-/-)beta(+/-)) were bred to the Ob/Ob mice. Ob/Ob-PGC-1alpha(-/ )beta(+/-) hearts exhibited dramatically reduced mitochondrial respiratory capacity. Finally, the mitochondrial biogenic response was triggered in H9C2 myotubes by exposure to oleate, an effect that was blunted with shRNA-mediated PGC-1 "knockdown". We conclude that PGC-1 signaling is important for the adaptive cardiac mitochondrial biogenic response that occurs during the early stages of insulin resistance. This response occurs in a cell autonomous manner and likely involves exposure to high levels of free fatty acids. PMID- 22080104 TI - Touch perception throughout working life: effects of age and expertise. AB - Fine motor skills including precise tactile and haptic perception are essential to the manipulation of objects. With increasing age, one's perception decreases; however, little is known about the state of touch perception in middle-aged adults. This study investigated the extent to which the decline in touch perception affects adults throughout their working life. In addition, the influence of work-related expertise on tactile and haptic perception was examined in an attempt to determine whether expertise, in the form of the frequent use of the fingers, affects perception and counters age-related losses. The study was conducted with subjects from three age groups (18-25, 34-46, and 54-65 years) with two levels of expertise. Expertise was classified by the subjects' occupations. Five sensory tasks of touch perception were conducted. The results confirmed age-related changes in tactile perception over the span of one's working life. Older workers were proven to have lower tactile performance than younger adults. However, middle-aged workers were hardly affected by the perception losses and did not differ significantly from younger adults. Work related expertise was not proven to either affect tactile and haptic perception or counteract age-related declines. We conclude that the age-related decline gets steeper in the late working life and that specific work-related expertise does not lead to generally improved touch perception that would result in lower thresholds and improved performance in non-expertise specific tasks. PMID- 22080105 TI - Postural effects of imagined leg pain as a function of hypnotizability. AB - It has been shown that, in subjects with high hypnotizability (Highs), imagined somatosensory stimulation can involuntarily activate the neural circuits involved in the modulation of reflex action. In this vein, aim of the study was to investigate whether the imagery of nociceptive stimulation in one leg may produce both subjective experience of pain and congruent postural adjustments during normal upright stance. The displacement of the centre of pressure (CoP) was studied during imagery of leg pain (LP) and during the control conditions of imagery of tactile stimulation of the same leg and of throat pain (TP) in 12 Highs and 12 low hypnotizable subjects (Lows). The results showed that the vividness of imagery was higher in Highs than in Lows for all tasks and that only Highs reported actually feeling pain during LP and TP. Congruently, during LP only Highs displaced their CoP towards the leg opposite to the one that was the object of painful imagery and increased their CoP mean velocity and area of excursion. Since the Highs' postural changes were not accounted for only by vividness of imagery and perceived pain intensity, high hypnotizability is apparently responsible for part of the postural effects of pain imagery. PMID- 22080107 TI - Study on electrochemical oxidation behaviors and the diffusion mechanism of hydroquinone at pre-anodized carbon paste electrode by cyclic voltammetry. AB - A functional pre-anodized carbon paste electrode (PACPE) was constructed by using successive cyclic voltammetry. The electrochemical oxidation behaviors of hydroquinone (HQ) were carefully investigated by various electrochemical techniques. The diffusion mechanism of HQ has been put forward for the first time. The driving force for the HQ transport towards anode not only related to the concentration diffusion but also depended on the transport of H(+) in the feed phase along a concentration gradient towards the cathode. The results indicated that the PACPE exhibited excellent electrocatalytic activity towards the oxidation of HQ. Compared with the bare carbon paste electrode, the oxidation and reduction peak separation (DeltaE(p)) of HQ at the PACPE has been decreased from 578 to 83 mV. Under the optimum conditions, the oxidation peak current was linear with HQ concentration in the range of 4 * 10(-7) to 1.0 * 10(-4) M with the linear correlation coefficient of 0.9986. The detection limit was 1.05 * 10( 7) M. This method can be successfully applied to the determination of HQ in wastewater. PMID- 22080106 TI - Genome-wide analysis of mutagenesis bias and context sensitivity of N-methyl-N' nitro-N-nitrosoguanidine (NTG). AB - We have analyzed the mutation spectrum of N-methyl-N'-nitro-N-nitrosoguanidine (NTG) from a set of 4099 mutations identified from whole-genome sequencing of 32 E. coli strains mutagenized with NTG. These data permit precise measurement of NTG's bias for G/C to A/T transitions (96.6% of all mutations) and also show that NTG mutagenesis is strongly sensitive to context, favoring guanine residues preceded by purines by five-fold over those preceded by pyrimidines. These data give confident estimates for the GC bias and transition/transversion ratios of NTG mutagenesis, which could not be estimated confidently from previous, much smaller datasets. PMID- 22080108 TI - Preduodenal portal vein, intestinal malrotation, polysplenia, and interruption of the inferior vena cava: a review of anatomical anomalies associated with gastric cancer. AB - PURPOSE: Anatomical anomalies of visceral organs associated with gastric cancer are extremely rare. Here, we report a case of preduodenal portal vein (PDPV), intestinal malrotation, interruption of the inferior vena cava (IVC), and polysplenia associated with gastric cancer in an adult patient, together with a review of the literature on the anomalies of visceral organs associated with gastric cancer. METHODS: We describe the diagnosis and surgical treatment in a 63 year-old man who had a preoperative diagnosis of PDPV, intestinal malrotation, interruption of the IVC with azygos continuation, and polysplenia associated with gastric cancer. Fifteen reports, in the English literature up to 2011, on visceral organ anomalies detected in gastric cancer patients were identified by searching Medline. RESULTS: All of the 15 cases of anomalies associated with gastric cancer, including the present case, were correctly diagnosed by preoperative imaging. Situs anomaly was the most frequent anatomical anomaly detected, and PDPV was observed in only four cases. In 12 cases, gastrectomy was performed, and gastrojejunostomy was done in 1 case. CONCLUSIONS: Although embryological anomalies such as PDPV, intestinal malrotation, interruption of the IVC, and polysplenia are rarely encountered in abdominal surgery, surgeons must be aware of their possible existence and be able to recognize them to avoid major intraoperative injuries. PMID- 22080109 TI - Functional aspects of the coracoclavicular space. AB - BACKGROUND: The coracoclavicular joint has been described as an articulation found inconstantly between the coracoid process and clavicle. We often observe a small space bordered by the fascia which covers the anterior surface of the subclavius muscle and the coracoclavicular ligament. The aim of this study was to observe the space in detail and to discuss the functional role of the coracoclavicular joint. MATERIALS AND METHODS: Sixteen shoulder girdles from eight Japanese cadavers were used in this study. The scapula, clavicle, and anterior half of the first rib were extracted en bloc together with the subclavius muscle and the surrounding fascia. After observing the motion of the scapula and clavicle, we investigated macroscopically the attachments of the coracoclavicular ligaments and the subclavius muscle, and the extension of the fascia. RESULTS: The fascia divided laterally into two sheets: the anterior sheet attached to the trapezoid ligament and the posterior to the conoid ligament. Among the two sheets, the coracoclavicular ligaments, coracoid process, and clavicle, a small space was observed. This small space can be recognized as a part of the coracoclavicular joint. When manually moving the inferior angle of the scapula with the sternal end of the clavicle fixed, we observed that the clavicle collided with the trapezoid ligament on the superior surface of the coracoid process within the space and that the scapular motion was restricted by this collision. CONCLUSION: The coracoclavicular joint could be much more recognizable than in previous papers and play an important role in the normal function of the shoulder joint. LEVEL OF EVIDENCE: Basic science study. PMID- 22080110 TI - What is the best anesthetic for ICD implants? PMID- 22080111 TI - Components of safe propofol sedation: defining the formula. PMID- 22080112 TI - Shrimp invertebrate lysozyme i-lyz: gene structure, molecular model and response of c and i lysozymes to lipopolysaccharide (LPS). AB - The invertebrate lysozyme (i-lyz or destabilase) is present in shrimp. This protein may have a function as a peptidoglycan-breaking enzyme and as a peptidase. Shrimp is commonly infected with Vibrio sp., a Gram-negative bacteria, and it is known that the c-lyz (similar to chicken lysozyme) is active against these bacteria. To further understand the regulation of lysozymes, we determined the gene sequence and modeled the protein structure of i-lyz. In addition, the expression of i-lyz and c-lyz in response to lipopolysaccharide (LPS) was studied. The shrimp i-lyz gene is interrupted by two introns with canonical splice junctions. The expression of the shrimp i-lyz was transiently down regulated after LPS injection followed by induction after 6 h in hepatopancreas. In contrast, c-lyz was up-regulated in hepatopancreas 4 h post-injection and slightly down-regulated in gills. The L. vannamei i-lyz does not contain the catalytic residues for muramidase (glycohydrolase) neither isopeptidase activities; however, it is known that the antibacterial activity does not solely rely on the enzymatic activity of the protein. The study of invertebrate lysozyme will increase our understanding of the regulatory process of the defense mechanisms. PMID- 22080113 TI - Homozygous deletion of a gene-free region of 4p15 in a child with multiple anomalies: could biallelic loss of conserved, non-coding elements lead to a phenotype? AB - We report a male patient, offspring of a consanguineous marriage between first cousins, with cognitive impairment, autistic-like behavior, deafness, postaxial polydactyly, and mild dysmorphic features. aCGH revealed a 600 kb homozygous deletion of 4p15.1 (from 33.553 to 34.159 Mb in NCBI36 hg18) encoding several transcripts of unknown function. Both parents are heterozygous for the deletion and the non-affected brother is homozygous for the normal alleles. We hypothesize that this deletion is likely to contribute to the phenotype of the patient. This case underlines the contribution of aCGH in discovering potentially pathogenic CNVs in consanguineous matings. PMID- 22080114 TI - Light-driven molecular shuttles modified on silicon nanowires. AB - Immobilization of light-driven molecular shuttles onto the surface of the silicon nanowires (SiNWs) was realized. The alpha-cyclodextrins as the shuttles could be reversibly translocated along the thread by the optical stimuli. Such SiNWs-based molecular shuttles also exhibited sequential logic with optical stimuli as the input and fluorescence as the output. PMID- 22080115 TI - Atmospheric deposition and storm induced runoff of heavy metals from different impermeable urban surfaces. AB - Contaminants deposited on impermeable surfaces migrate to stormwater following rainfall events, but accurately quantifying their spatial and temporal yields useful for mitigation purposes is challenging. To overcome limitations in current sampling methods, a system was developed for rapid quantification of contaminant build-up and wash-off dynamics from different impervious surfaces. Thin boards constructed of concrete and two types of asphalt were deployed at different locations of a large carpark to capture spatially distributed contaminants from dry atmospheric deposition over specified periods of time. Following experimental exposure time, the boards were then placed under a rainfall simulator in the laboratory to generate contaminant runoff under controlled conditions. Single parameter effects including surface roughness and material composition, number of antecedent dry days, rain intensity, and water quality on contaminant build-up and wash-off yields could be investigated. The method was applied to quantify spatial differences in deposition rates of contaminants (TSS, zinc, copper and lead) at two locations varying in their distance to vehicle traffic. Results showed that boards exposed at an unused part of the carpark >50 m from vehicular traffic captured similar amounts of contaminants compared with boards that were exposed directly adjacent to the access route, indicating substantial atmospheric contaminant transport. Furthermore, differences in contaminant accumulation as a function of surface composition were observed. Runoff from asphalt boards yielded higher zinc loads compared with concrete surfaces, whereas runoff from concrete surfaces resulted in higher TSS concentrations attributed to its smoother surfaces. The application of this method enables relationships between individual contaminant behaviour and specific catchment characteristics to be investigated and provides a technique to derive site-specific build-up and wash-off functions required for modelling contaminant loads from impermeable surfaces. PMID- 22080116 TI - The host-seeking inhibitory peptide, Aea-HP-1, is made in the male accessory gland and transferred to the female during copulation. AB - Male accessory glands (MAGs) of insects are responsible for the production of many of the seminal fluid proteins and peptides that elicit physiological and behavioral responses in the post-mated female. In the yellow fever mosquito, Aedes aegypti, seminal fluid components are responsible for stimulating egg production, changing female behavior away from host-seeking toward egg-laying and mating refractoriness, but hitherto no behavior-modifying molecule from the MAGs has been structurally characterized. We now show using mass spectrometry and HPLC/ELISA that the MAG is a major site of synthesis of the biologically active decapeptide, Aea-HP-1 (pERPhPSLKTRFamide) that was first characterized by Matsumoto and colleagues in 1989 from mosquito head extracts and shown to have host-seeking inhibitory properties. The peptide is localized to the anterior portion of the MAG, occurs at high concentrations in the gland and is transferred to the female reproductive tract on copulation. Aea-HP-1 has a pyroglutamic acid at the N-terminus, an amidated carboxyl at the C-terminus and an unusual 4 hydroxyproline in position 4 of the peptide. The structure of the peptide with its blocked N- and C-termini confers resistance to metabolic inactivation by MAG peptidases; however the peptide persists for less than 2h in the female reproductive tract after copulation. Aea-HP-1 is not a ligand for the mosquito sex peptide/myoinhibitory peptide receptor. A. aegypti often mate close to the host and therefore it is possible that male-derived Aea-HP-1 induces short-term changes to female host-seeking behavior to reduce potentially lethal encounters with hosts soon after insemination. PMID- 22080117 TI - Microautophagy: lesser-known self-eating. AB - Microautophagy, the non-selective lysosomal degradative process, involves direct engulfment of cytoplasmic cargo at a boundary membrane by autophagic tubes, which mediate both invagination and vesicle scission into the lumen. With its constitutive characteristics, microautophagy of soluble substrates can be induced by nitrogen starvation or rapamycin via regulatory signaling complex pathways. The maintenance of organellar size, membrane homeostasis, and cell survival under nitrogen restriction are the main functions of microautophagy. In addition, microautophagy is coordinated with and complements macroautophagy, chaperone mediated autophagy, and other self-eating pathways. Three forms of selective microautophagy, including micropexophagy, piecemeal microautophagy of the nucleus, and micromitophagy, share common ground with microautophagy to some degree. As the accumulation of experimental data, the precise mechanisms that govern microautophagy are becoming more appreciated. Here, we review the microautophagic molecular machinery, its physiological functions, and relevance to human diseases, especially in diseases involving multivesicular bodies and multivesicular lysosomes. PMID- 22080118 TI - Wounds, functional disability, and indwelling devices are associated with cocolonization by methicillin-resistant Staphylococcus aureus and vancomycin resistant enterococci in southeast Michigan. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) remains sensitive to vancomycin; when vancomycin-resistant S. aureus (VRSA) emerges, treatment becomes more complex. VRSA emergence is attributed to conjugative transfer of the vancomycin-resistance gene cluster from vancomycin-resistant enterococci (VRE) to MRSA. Because cocolonization with MRSA and VRE precedes VRSA development, this study investigates the epidemiology of cocolonization in skilled nursing facility (SNF) residents at high risk for MRSA or VRE colonization. METHODS: A prospective observational study conducted at 15 SNFs in southeast Michigan. Overall, 178 residents (90 with indwelling urinary catheters and/or feeding tubes and 88 device-free) were cultured monthly for MRSA and VRE, and clinical data were recorded. RESULTS: The incidence of MRSA/VRE cocolonization among residents with indwelling devices was 6.5 per 100 resident-months; 5.2 (95% confidence interval [CI]: 1.49-18.1) times that among those without devices. MRSA/VRE cocolonization in the device group occurred most frequently in wounds (4.1 per 100 resident months). In a logistic regression analysis limited to residents with devices, functional disability (rate ratio [RR], 1.3; 95% CI: 1.1-1.4) and wound presence (RR, 3.4; 95% CI: 1.4-8.6) were independent risk factors of cocolonization. CONCLUSIONS: In a population of SNF residents, individuals with indwelling devices who also had functional disability or wounds were at greatest risk of MRSA/VRE cocolonization. These individuals should be routinely monitored for the presence of VRSA colonization. PMID- 22080119 TI - Current epidemiology and trends in invasive Haemophilus influenzae disease- United States, 1989-2008. AB - BACKGROUND: With the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines, there has been a dramatic reduction of Hib disease in young children and the epidemiological trends of invasive H. influenzae have shifted. METHODS: Data were collected from active surveillance for invasive H. influenzae disease conducted through Active Bacterial Core surveillance sites during 1989 2008. RESULTS: During 1999-2008, the estimated mean annual incidence of H. influenzae infection was 1.62 cases per 100 000 population; 15.3% of cases were fatal. Incidence was higher among adults aged >=65 years, compared with other age groups. The largest burden of disease among children aged <5 years was in infants aged <1 year; many of these cases occurred during the first month of life in preterm or low-birth weight infants. An estimated 10% of the total burden of disease among children aged <5 years occurred in American Indian and Alaska Native children. During 1989-2008, 7559 cases of H. influenzae disease were reported from Active Bacterial Core surveillance sites. Small increases in the incidence of serotypes a, e, and f were observed during 1989-2008. The largest of these increases was in serotype f and was primarily among adults aged >=18 years. CONCLUSIONS: Since the introduction of Hib conjugate vaccines, the incidence of invasive disease caused by H. influenzae in the United States has decreased dramatically; however, a considerable burden of non-Hib disease is still present in the oldest and youngest age groups. There is no evidence of substantial replacement disease with non-b serotypes in young children in the United States. PMID- 22080120 TI - Pneumothorax in a young man in Brooklyn, New York. PMID- 22080123 TI - Variant angina in the setting of food-borne botulism. PMID- 22080121 TI - Immunologic criteria are poor predictors of virologic outcome: implications for HIV treatment monitoring in resource-limited settings. AB - BACKGROUND: Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria. METHODS: We assessed the performance of CD4 cell criteria to predict virologic outcomes in a large ART program in Nigeria. Laboratory monitoring consists of CD4 cell count and VL at baseline, then every 6 months. Failure was defined as 2 consecutive VLs >1000 copies/mL after at least 6 months of ART. Virologic outcomes were compared with the 3 WHO-defined immunologic failure criteria. RESULTS: A total of 9690 patients were included in the analysis (median follow-up, 33.2 months). A total of 1225 patients experienced failure by both immunologic and virologic criteria, 872 by virologic criteria only, and 1897 by immunologic criteria only. The sensitivity of CD4 cell criteria to detect viral failure was 58%, specificity was 75%, and the positive-predictive value was 39%. For patients with both virologic and immunologic failure, VL criteria identified failure significantly earlier than CD4 cell criteria (median, 10.4 vs 15.6 months; P < .0001). CONCLUSIONS: Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus. PMID- 22080124 TI - Does oseltamivir really reduce complications of influenza? PMID- 22080126 TI - Chronic bacterial prostatitis: enterococcal disease? PMID- 22080130 TI - Invasive mold infections in chronic granulomatous disease: a 25-year retrospective survey. AB - BACKGROUND: Invasive fungal infection (IFI) represents a life-threatening condition for patients with chronic granulomatous disease (CGD) and causes one third of deaths in this population. This study offers a descriptive review of invasive mold infection (mIFI) in children with CGD over an extended period of time. METHODS: In a cohort of patients with CGD registered in the French National database for Primary Immunodeficiency, we performed a retrospective review of proven mIFI episodes (European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group 2008 criteria) occurring from 1984 through 2009. RESULTS: Twenty-nine proven mIFIs were identified in 24 patients. Thirteen (54%) of 24 children were receiving itraconazole prophylaxis. Seven episodes were caused by Aspergillus fumigatus, 10 by Aspergillus nidulans, 2 by Aspergillus species, and 6 by other opportunistic molds (4 patients only had positive pathological examination findings). First proven mIFI occurred later in the group that received itraconazole than in the group without (median time to mIFI, 10 vs 4 years; P < .01), with a higher proportion of infections due to A. nidulans and other opportunistic molds (P < .05). Course of IFI was complex, with the median duration of therapy and hospitalization reaching 446 and 153 days, respectively. Combined antifungal therapy was commonly used. Four patients received geno-identical hematopoietic stem cell transplantation as salvage therapy. Global cure rate among the cohort reached 75%, but sequelae were frequent. Prognosis has improved over time (43% mortality during 1985-1990 vs 6% thereafter; P = .06). Mortality tended to be lower in the group that recieved itraconazole prophylaxis but at the cost of a longer duration of therapy among cured patients. CONCLUSIONS: Management of mIFI remains challenging in patients with CGD, but significant improvements have been made over the past decade. PMID- 22080131 TI - Measles among US-bound refugees from Malaysia to California, Maryland, North Carolina, and Wisconsin, August-September 2011. PMID- 22080139 TI - The transition of breast cancer treatment and Japan Clinical Oncology Group research over two decades. AB - The Japanese Breast Cancer Study Group (JABCSG) was established before the Japan Clinical Oncology Group (JCOG). The JABCSG became the JCOG Breast Cancer Group 20 years ago. The first chairman of the Breast Cancer Group was Dr Kaoru Abe (National Cancer Center Hospital). Since 1978, five doctors have chaired the Breast Cancer Group. Sixteen clinical trials (eight phase III and eight phase I/II) have been conducted by the Breast Cancer Group since 1985. The Breast Cancer Group was restructured in 2010, and in June 2011 a new clinical trial (JCOG 1017) was initiated. Standard treatment for breast cancer (surgery, radiotherapy and systemic therapy) has changed dramatically over the last two decades. This review describes the transition of breast cancer treatment along with the history of JCOG research in this setting. PMID- 22080138 TI - Somatic mutations contribute to genotypic diversity in sterile and fertile populations of the threatened shrub, Grevillea rhizomatosa (Proteaceae). AB - BACKGROUND AND AIMS: Grevillea rhizomatosa is a spreading shrub which exhibits multiple breeding strategies within a narrow area in the fire-prone heathlands of eastern Australia. Reproductive strategies include self-compatibility, self incompatibility and clonality (with and without sterility). The close proximity of contrasting breeding systems provides an opportunity to explore the evolution of sterility and to compare and contrast the origins of genotypic diversity (recombinant or somatic) against degrees of sexual expression. METHODS: ISSR markers for 120 band positions (putative loci) were used to compare genetic diversity among five populations at a macro-scale of 5 m between samples (n = 244 shrubs), and at a micro-scale of nearest neighbours for all plants in five 25 m(2) quadrats with contrasting fertilities (n = 162 shrubs). Nearest-neighbour sampling included several clusters of connected ramets. Matrix incompatibility (MIC) analyses were used to evaluate the relative contribution of recombination and somatic mutation to genotype diversity. KEY RESULTS: High levels of genotypic diversity were found in all populations regardless of fertilities (fertile populations, G/N >= 0.94; sterile populations, G/N >= 0.97) and most sterile populations had a unique genetic profile. Somatic mutations were detected along connected ramets in ten out of 42 ramet clusters. MIC analyses showed that somatic mutations have contributed to diversity in all populations and particularly so in sterile populations. CONCLUSIONS: Somatic mutations contribute significantly to gene diversity in sterile populations of Grevillea rhizomatosa, the accumulation of which is the likely cause of male and female sterility. High levels of genetic diversity therefore may not always be synonymous with sexual fitness and genetic health. We hypothesize that frequent fires drive selection for clonal reproduction, at the cost of flowering such that sexual functions are not maintained through selection, and the build-up of somatic mutations in meristems results in high genotype diversity at the cost of pollen and ovule fertilities. PMID- 22080140 TI - Involvement of the oestrogenic receptors in superior mesenteric ganglion on the ovarian steroidogenesis in rat. AB - Oestradiol (E(2)) is a key hormone in the regulation of reproductive processes. The aims of this work were a) to examine the distributions of oestrogen receptor alpha (ERalpha) and ERbeta in the neurons of the superior mesenteric ganglion (SMG) in the oestrus stage by immunohistochemistry, b) to demonstrate whether E(2) in the SMG modifies progesterone (P(4)), androstenedione (A(2)) and nitrite release in the ovarian compartment on oestrus day and c) to demonstrate whether E(2) in the ganglion modifies the activity and gene expression in the ovary of the steroidogenic enzymes 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD). The ex vivo SMG-ovarian nervous plexus-ovary system was used. E(2), tamoxifen (Txf) and E(2) plus Txf were added in the ganglion to measure ovarian P(4) release, while E(2) alone was added to measure ovarian A(2) and nitrites release. Immunohistochemistry revealed cytoplasmic ERalpha immunoreactivity only in the neural somas in the SMG. E(2) increased ovarian P(4) and A(2) release at 15, 30 and 60 min but decreased nitrites. The activity and gene expression of 3beta-HSD increased, while the activity and gene expression of 20alpha-HSD did not show changes with respect to the control. Txf in the ganglion diminished P(4) release only at 60 min. E(2) plus Txf in the ganglion reverted the effect of E(2) alone and the inhibitory effect of Txf. The results of this study demonstrate that ERalpha activation in the SMG has an impact on ovarian steroidogenesis in rats, thus providing evidence for the critical role of peripheral system neurons in the control of ovarian functions under normal and pathological conditions. PMID- 22080141 TI - FSH withdrawal improves developmental competence of oocytes in the bovine model. AB - Combinations of genetic, environmental, and management factors are suspected to explain the loss in fertility observed for over 20 years in dairy cows. In some cases, IVF is used. When compared with in vivo embryo production, IVF resulted in low success rates until the FSH coasting process (FSH starvation after superstimulation) was introduced in 2002. Increased competence associated with FSH withdrawal of aspirated oocyte for in vitro maturation and IVF has not been optimized nor explained yet. The goal here was to determine and characterize the optimal oocyte competence acquisition window during the coasting period by determining blastocyst rates and follicular cohort development. Commercial milking cycling cows (n=6) were stimulated with 3 days of FSH (6*40 mg NIH Folltropin-V given at 12 h intervals) followed by a coasting period of 20, 44, 68, or 92 h. Each animal was exposed to the four conditions and served as its own control. At the scheduled time, transvaginal aspirations of immature oocytes were performed followed by IVF of half the oocytes. The outcomes were as follows: i) FSH coasting was optimal at a defined period: between 44 and 68 h of coasting; ii) The best estimated coasting duration was ~54+/-7 h; iii) Under these conditions, the best statistical blastocyst rate estimation was ~70%; iv) Between 44 and 68 h of coasting, follicle size group proportions were similar; v) Follicle diameter was not linearly associated with competence. In conclusion, coasting duration is critical to harvest the oocytes at the right moment of follicular differentiation. PMID- 22080142 TI - Associations of hip circumference and height with incidence of type 2 diabetes: the Isfahan diabetes prevention study. AB - The aim of this study was to determine the effects of hip circumference (HC) and height on diabetes incidence in non-diabetic first-degree relatives (FDRs) of patients with type 2 diabetes. A total of 1,092 (254 men and 838 women) non diabetics FDRs >= 30 years old in 2003-2005 were followed through 2010 for the occurrence of type 2 diabetes. At baseline and through follow-ups, participants were underwent a standard 75 g 2-h oral glucose tolerance test. The incidence of type 2 diabetes was 17.0 (95% CI: 13.7, 20.2) (13.0 men and 18.1 women) per 1,000 person-year based on 6,015 person-years of follow-up. Height was inversely associated with diabetes incidence. The age-, gender-, and waist-adjusted relative risk (95% CI) of diabetes was 0.54 (0.31, 0.93) for highest quartile of height and 0.59 (0.25, 1.37) for highest quartile of HC compared with lowest quartile. These data indicate that height was inversely associated with diabetes incidence, independently of gender among FDRs of patients with type 2 diabetes. PMID- 22080143 TI - A new ratiometric fluorescence detection of heparin based on the combination of the aggregation-induced fluorescence quenching and enhancement phenomena. AB - A new ratiometric fluorescence detection of heparin is reported with the ensemble of 1 and 2. This method is based on the respective ACQ (aggregation-caused quenched emission) and AIE (aggregation-induced emission) features of anthracene and tetraphenylethene. DLS, CLSM and fluorescent spectral investigations suggest that the variation of the fluorescence intensity ratio I(497)/I(421) is due to the formation of aggregates of 1 and 2 with heparin. Moreover, this ratiometric fluorescence method can be used to distinguish heparin from its analogues (HA, Dex). In order to demonstrate the practical utilization of this ratiometric fluorescence method, the fluorescence spectra of the ensemble of 1 and 2 were measured in the presence of serum, and the results indicate that it is possible to eliminate the interferences from other biomolecules by either subtracting the background fluorescence intensities or lowering the pH values of the sample solutions. PMID- 22080144 TI - Family community integration and maternal mental health. AB - While the majority of women with mental health problems (MHPs) are mothers, little is known about the community integration (CI) of these women and their children. Given that poorer mental health status has been linked with lower CI, CI has become a long standing goal of mental health policy. Data from a national survey examined the association of maternal mental health status with the physical, social, and psychological integration of families. After adjusting for sociodemographics, mothers with MHPs reported similar physical integration but less social and psychological integration. Interventions focused on improving social networks, scarce resources, and neighborhood safety are needed for families impacted by maternal MHPs. PMID- 22080145 TI - Algicidal activity of thiazolidinedione derivatives against harmful algal blooming species. AB - Thiazolidinedione (TD) derivatives exhibit algicidal activity against harmful algal blooming species such as Chattonella marina, Heterosigma akashiwo, and Cochlodinium polykrikoides, as reported previously. In this study, the efficacies and selectivities of TD derivatives were tested by analyzing the structure activity relationships of various TD derivatives. To investigate structure activity relationships for growth inhibition of harmful algae, we added a methylene group between the cyclohexyl ring and oxygen of 5-(3-chloro-4 hydroxybenzylidene)-TD, which decreased the inhibitory potency of compound 17. Interestingly, another addition of a methylene group significantly increased the inhibitory potency against C. polykrikoides. The addition of 1 MUM compound 17 resulted in the cell rupture of harmful algae after less than 10 h incubation at 20 degrees C. Compound 17 was applied to both harmful and non-harmful algae and showed a drastic reduction in the efficiency of photosystem II, resulting in reduced photosynthetic oxygen evolution. Compound 17 at a 5 MUM concentration destroyed all of the harmful algae, while algicidal activity against non-harmful algae did not exceed 30% of the control within the concentration range tested. In contrast, a herbicide, 3-(3,4-dichlorophenyl)-1,1-dimethylurea, tested at a 5 MUM concentration, exhibited 40-70% algicidal activity relative to that of the control against both harmful and non-harmful algae. Compound 17 is a promising lead compound for the development of algicides to control harmful algal blooming species. PMID- 22080146 TI - Course of serum 25-hydroxyvitamin D(3) status and its influencing factors in adults undergoing allogeneic hematopoietic cell transplantation. AB - Hypovitaminosis D (<30 ng/ml) is highly prevalent in allogeneic hematopoietic cell transplantation (alloHCT), but the relevance of influencing factors for serum 25-hydroxyvitamin D(3) [25(OH)D(3)] status in adult patients remains unknown. We are the first to have prospectively assessed 25(OH)D(3) status and its influencing factors in 102 patients before and at days +30 and +100 after alloHCT. Among others, we evaluated age, gender, weight, fat mass, season, sun exposure habits, and dietary and supplemental vitamin D intake as factors potentially influencing baseline vitamin D status in uni- and multivariate linear regression analysis. Furthermore, we investigated the impact of changes in fat mass, duration of parenteral nutrition, and acute graft-versus-host disease (aGVHD) on the course of serum 25(OH)D(3). Baseline 25(OH)D(3) concentrations were 16.4 +/- 8.9 ng/ml, revealing that the majority (89%) had concentrations beneath the normal range. In multivariate linear regression model, only higher body fat mass remained an independent risk factor for reduced baseline 25(OH)D(3) concentrations (P = 0.007). In the early post-transplant period, 25(OH)D(3) status remained low, revealing a tendency to further deterioration, especially in patients with corticosteroid-treated aGVHD (>=II). Reduced vitamin D status was very common in these patients before and after alloHCT, whereby the most important influencing factors, namely season and dietary factors seem to have little impact. Our findings suggest that monitoring and if necessary, correcting vitamin D status may be indicated at regular intervals before alloHCT and during long-term follow-up. Further investigations of these patients' vitamin D requirements are needed, especially if they are on long-term corticosteroids. PMID- 22080147 TI - Hemophagocytic syndrome associated with visceral leishmaniasis in an immunocompetent adult-case report and review of the literature. PMID- 22080148 TI - Extravascular hemolytic attack after eculizumab therapy for paroxysmal nocturnal hemoglobinuria. PMID- 22080149 TI - A large family with MYH9 disorder caused by E1841K mutation suffering from serious kidney and hearing impairment and cataracts. PMID- 22080150 TI - Cytoarchitecture of mouse and human subventricular zone in developing cerebral neocortex. AB - During cerebral neocortical development, excitatory neurons are generated from radial glial cells in the ventricular zone (VZ) or from secondary progenitor cells in the subventricular zone (SVZ); these neurons then migrate toward the pial surface. We have observed that post-mitotic neurons generated directly in the VZ accumulated just above the VZ with a multipolar morphology, while secondary progenitor cells having a long ascending process left the VZ faster than the post-mitotic neurons. Recent observations of human developing neocortex have revealed the existence of radial glia-like progenitors (oRG cells) in the SVZ. This type of progenitor was first thought to be human specific; however, similar cells have also been found in mouse neocortex, and the morphology of these cells resembled that of some of the secondary progenitor cells that we had previously observed, suggesting the existence of a common architecture for the developing neocortex among mammals. In this review, we discuss the nature of the SVZ and its similarities and differences between humans and mice. PMID- 22080151 TI - Directional remapping in tactile inter-finger apparent motion: a motion aftereffect study. AB - Tactile motion provides critical information for perception and manipulation of objects in touch. Perceived directions of tactile motion are primarily defined in the environmental coordinate, which means they change drastically with body posture even when the same skin sensors are stimulated. Despite the ecological importance of this perceptual constancy, the sensory processing underlying tactile directional remapping remains poorly understood. The present study psychophysically investigated the mechanisms underlying directional remapping in human tactile motion processing by examining whether finger posture modulates the direction of the tactile motion aftereffect (MAE) induced by inter-finger apparent motions. We introduced conflicts in the adaptation direction between somatotopic and environmental spaces by having participants change their finger posture between adaptation and test phases. In a critical condition, they touched stimulators with crossed index and middle fingers during adaptation but with uncrossed fingers during tests. Since the adaptation effect was incongruent between the somatotopic and environmental spaces, the direction of the MAE reflects the coordinate of tactile motion processing. The results demonstrated that the tactile MAE was induced in accordance with the motion direction determined by the environmental rather than the somatotopic space. In addition, it was found that though the physical adaptation of the test fingers was not changed, the tactile MAE disappeared when the adaptation stimuli were vertically aligned or when subjective motion perception was suppressed during adaptation. We also found that the tactile MAE, measured with our procedure, did not transfer across different hands, which implies that the observed MAEs mainly reflect neural adaptations occurring within sensor-specific, tactile-specific processing. The present findings provide a novel behavioral method to analyze the neural representation for directional remapping of tactile motion within tactile sensory processing in the human brain. PMID- 22080152 TI - Identification of cortical lamination in awake monkeys by high resolution magnetic resonance imaging. AB - Brodmann divided the neocortex into 47 different cortical areas based on histological differences in laminar myeloarchitectonic and cytoarchitectonic defined structure. The ability to do so in vivo with anatomical magnetic resonance (MR) methods in awake subjects would be extremely advantageous for many functional studies. However, due to the limitations of spatial resolution and contrast, this has been difficult to achieve in awake subjects. Here, we report that by using a combination of MR microscopy and novel contrast effects, cortical layers can be delineated in the visual cortex of awake subjects (nonhuman primates) at 4.7 T. We obtained data from 30-min acquisitions at voxel size of 62.5 * 62.5 * 1000 MUm(3) (4 nl). Both the phase and magnitude components of the T(2)*-weighted image were used to generate laminar profiles which are believed to reflect variations in myelin and local cell density content across cortical depth. Based on this, we were able to identify six layers characteristic of the striate cortex (V1). These were the stripe of Kaes-Bechterew (in layer II/III), the stripe of Gennari (in layer IV), the inner band of Baillarger (in layer V), as well as three sub-layers within layer IV (IVa, IVb, and IVc). Furthermore, we found that the laminar structure of two extrastriate visual cortex (V2, V4) can also be detected. Following the tradition of Brodmann, this significant improvement in cortical laminar visualization should make it possible to discriminate cortical regions in awake subjects corresponding to differences in myeloarchitecture and cytoarchitecture. PMID- 22080154 TI - Highly enantioselective Mukaiyama aldol reaction in aqueous conditions using a chiral iron(II) bipyridine catalyst. AB - A highly enantioselective method for the catalytic Mukaiyama aldol reaction of silyl enol ethers with aldehydes in aqueous conditions was developed. The desired aldol products were obtained in excellent yields, diastereo- and enantioselectivities. Structural evidence of the pre-catalyst revealed an unprecedented heptadentate Fe(II) complex with the chiral bipyridine ligand. PMID- 22080153 TI - Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress. AB - Nucleus-encoded regulatory factors are major contributors to mitochondrial biogenesis and function. Several act within the organelle to regulate mitochondrial transcription and translation while others direct the expression of nuclear genes encoding the respiratory chain and other oxidative functions. Loss of-function studies for many of these factors reveal a wide spectrum of phenotypes. These range from embryonic lethality and severe respiratory chain deficiency to relatively mild mitochondrial defects seen only under conditions of physiological stress. The PGC-1 family of regulated coactivators (PGC-1alpha, PGC 1beta and PRC) plays an important integrative role through their interactions with transcription factors (NRF-1, NRF-2, ERRalpha, CREB, YY1 and others) that control respiratory gene expression. In addition, recent evidence suggests that PGC-1 coactivators may balance the cellular response to oxidant stress by promoting a pro-oxidant environment or by orchestrating an inflammatory response to severe metabolic stress. These pathways may serve as essential links between the energy generating functions of mitochondria and the cellular REDOX environment associated with longevity, senescence and disease. This article is part of a Special Issue entitled: Mitochondrial Gene Expression. PMID- 22080155 TI - Axon cytoskeleton proteins specifically modulate oligodendrocyte growth and differentiation in vitro. AB - In multiple sclerosis (MS) remyelination by oligodendrocytes (OL) is incomplete, and it is associated with a decrease in axonal neurofilaments (NF) and tubulin (TUB). To determine whether these proteins could participate directly in MS remyelination failure, or indirectly through proteins that are co-associated, we have analysed their effects in pure OL cultures. Rat brain NF fractions, recovered by successive centrifugations increase either OL progenitor (OLP) proliferation (2nd pellet, P2), or only their maturation (P5), whereas albumin, liver and skin proteins, as well as recombinant GFAP or purified actin were ineffective. NF (P2) copurify mainly with TUB, as well as with other proteins, like MAPs, Tau, spectrin beta2, and synapsin 2. These purified, or recombinant, proteins increased OLP proliferation without delaying their maturation, and appeared responsible for the proliferation observed with P2 fractions. Among putative signaling pathways mediating these effects Fyn kinase was not involved. Whereas NF did not alter the growth of cultured astrocytes, the NF associated proteins enhanced their proliferation. This suggests that NF and their associated proteins exert specific effects on OL development, broadening the field of axon oligodendrocyte interactions. In case of axon damage in vivo, extracellular release of such axonal proteins could regulate remyelination and astrocytic gliosis. PMID- 22080157 TI - Exposure to novel environment is characterized by an interaction of D1/NMDA receptors underlined by phosphorylation of the NMDA and AMPA receptor subunits and activation of ERK1/2 signaling, leading to epigenetic changes and gene expression in rat hippocampus. AB - Interactions between dopamine and glutamate receptors are essential for prefrontal cortical (PFC) and hippocampal cognitive functions. The hippocampus has been identified as a detector of a novel stimulus, where an association between incoming information and stored memories takes place. Further to our previous results which showed a strong synergistic interaction of dopamine D1 and glutamate NMDA receptors, the present study is going to investigate the functional status of that interaction in rats, following their exposure to a novel environment. Our results showed that the "spatial" novelty induced in rat hippocampus and PFC (a) a significant increase in phosphorylation of NMDA and AMPA receptor subunits, as well as a robust phosphorylation/activation of ERK1/2 signaling, which are both dependent on the concomitant stimulation of D1/NMDA receptors and are both abolished by habituation procedure, (b) chromatin remodeling events (phosphorylation-acetylation of histone H3) and (c) an increase in the immediate early genes (IEGs) c-Fos and zif-268 expression in the CA1 region of hippocampus, which is dependent on the co-activation of D1/NMDA and acetylcholine muscarinic receptors. In conclusion, our results clearly show that a strong synergistic interaction of D1/NMDA receptor is required for the novelty induced phosphorylation of NMDA and AMPA receptor subunits and for the robust activation of ERK1/2 signaling, leading to chromatin remodeling events and the expression of the IEGs c-Fos and zif-268, which are involved in the regulation of synaptic plasticity and memory consolidation. PMID- 22080156 TI - Riluzole elevates GLT-1 activity and levels in striatal astrocytes. AB - Drugs which upregulate astrocyte glutamate transport may be useful neuroprotective compounds by preventing excitotoxicity. We set up a new system to identify potential neuroprotective drugs which act through GLT-1. Primary mouse striatal astrocytes grown in the presence of the growth-factor supplement G5 express high levels of the functional glutamate transporter, GLT-1 (also known as EAAT2) as assessed by Western blotting and 3H-glutamate uptake assay, and levels decline following growth factor withdrawal. The GLT-1 transcriptional enhancer dexamethasone (0.1 or 1 MUM) was able to prevent loss of GLT-1 levels and activity following growth factor withdrawal. In contrast, ceftriaxone, a compound previously reported to enhance GLT-1 expression, failed to regulate GLT-1 in this system. The neuroprotective compound riluzole (100 MUM) upregulated GLT-1 levels and activity, through a mechanism that was not dependent on blockade of voltage sensitive ion channels, since zonasimide (1 mM) did not regulate GLT-1. Finally, CDP-choline (10 MUM-1 mM), a compound which promotes association of GLT-1/EAAT2 with lipid rafts was unable to prevent GLT-1 loss under these conditions. This observation extends the known pharmacological actions of riluzole, and suggests that this compound may exert its neuroprotective effects through an astrocyte dependent mechanism. PMID- 22080158 TI - An overview of consumer attitudes and beliefs about plant food supplements. AB - The use of dietary supplements is increasing globally and this includes the use of plant food supplements (PFS). A variety of factors may be influencing this increased consumption including the increasing number of older people in society, mistrust in conventional medicine and the perception that natural is healthy. Consumer studies in this area are limited, with a focus on dietary supplements in general, and complicated by the use of certain plant food supplements as herbal medicines. Research indicates that higher use of dietary supplements has been associated with being female, being more educated, having a higher income, being white and being older, however the drivers for consumption of supplements are complex, being influenced by both demographic and health-related factors. The aim of this paper is to provide an overview of current knowledge about the users and the determinants of usage of plant food supplements. With growing consumption of these products, the need for effective risk-benefit assessment becomes ever more important and an insight into who uses these types of products and why is an important starting point for any future science-based decisions made by policy makers, PFS manufacturers and ultimately by consumers themselves. PMID- 22080159 TI - 5-aminolevulinic acid (5-ALA)-induced fluorescence in intracerebral metastases: a retrospective study. AB - BACKGROUND: Microsurgical, circumferential stripping of intracerebral metastases often proves to be insufficient to prevent local tumor recurrence. OBJECTIVE: We were interested in the potential impact of 5-aminolevulinic acid (5-ALA)-induced fluorescence (5-AIF) as a diagnostic tool for the resection of intracerebral metastases. METHODS: A retrospective analysis was performed for 52 patients who underwent 5-AIF-guided resection for intracerebral mass lesions that histologically corresponded to metastases from tumors outside the central nervous system. The presence of ALA fluorescence in the tumor was determined in each patient. In 42 patients, fluorescence of the resection cavity after tumor removal was additionally recorded. Data were correlated with neuropathological findings in tissue specimens. RESULTS: A total of 32 of the 52 metastases (62%) exhibited 5-AIF in tumor parts. All 5-AIF-positive metastases exhibited an inhomogeneous fluorescence pattern. 5-AIF was neither associated with the histological type nor with the site of origin of the metastases. Residual fluorescence of the resection cavity was detected after macroscopically complete white light resection in 24 patients with 5-AIF positive metastases. Residual tumor tissue was histologically confirmed in 6 of 18 patients with available tissue specimens from such 5-AIF positive areas (33%). CONCLUSIONS: The majority of metastases (62%) were 5-AIF positive, suggesting a potential impact of 5-AIF for improved visualization of metastatic tumor tissue within the brain. However, residual 5-AIF after macroscopically complete resection of a metastasis needs to be interpreted with caution because of the limited specificity for detection of residual tumor tissue. PMID- 22080160 TI - Progress on ART--an exposure modelling tool for REACH. PMID- 22080162 TI - Advanced REACH Tool: development and application of the substance emission potential modifying factor. AB - The Advanced REACH Tool (ART) is an exposure assessment tool that combines mechanistically modelled inhalation exposure estimates with available exposure data using a Bayesian approach. The mechanistic model is based on nine independent principal modifying factors (MF). One of these MF is the substance emission potential, which addresses the intrinsic substance properties as determinants of the emission from a source. This paper describes the current knowledge and evidence on intrinsic characteristics of solids and liquids that determine the potential for their release into workplace air. The principal factor determining the release of aerosols from handling or processing powdered, granular, or pelletized materials is the dustiness of the material, as well as the weight fraction of the substance of interest in the powder and the moisture content. The partial vapour pressure is the main intrinsic factor determining the substance emission potential for emission of vapours. For generation of mist, the substance emission potential is determined by the viscosity of the liquid as well as the weight fraction of the substance of interest in the liquid. Within ART release of vapours is considered for substances with a partial vapour pressure at the process temperature of 10 Pa or more, while mist formation is considered for substances with a vapour pressure <= 10 Pa. Relative multipliers are assigned for most of the intrinsic factors, with the exception of the weight fraction and the vapour pressure, which is applied as a continuous variable in the estimation of the substance emission potential. Currently, estimation of substance emission potential is not available for fumes, fibres, and gases. The substance emission potential takes account of the latest thinking on emissions of dusts, mists, and vapours and in our view provides a good balance between theory and pragmatism. Expanding the knowledge base on substance emission potential will improve the predictive power of occupational exposure models and thereby the accuracy and precision of the exposure estimates. PMID- 22080161 TI - Advanced REACH Tool (ART): overview of version 1.0 and research needs. AB - This paper provides an outline of the Advanced REACH Tool (ART) version 1.0 and a discussion of how it could be further developed. ART is a higher tier exposure assessment tool that combines mechanistically modelled inhalation exposure predictions with available exposure data using a Bayesian approach. ART assesses exposure for scenarios across different plants and sites. Estimates are provided for different percentiles of the exposure distribution and confidence intervals around the estimate. It also produces exposure estimates in the absence of data, but uncertainty of the estimates will decrease when results of exposure measurements are included. The tool has been calibrated using a broad range of exposure data and provides estimates for exposure to vapours, mists, and dusts. ART has a robust and stable conceptual basis but will be refined in the future and should therefore be considered an evolving system. High-priority areas for future research are identified in this paper and include the integration of partially analogous measurement series, inclusion of company and site-specific assessments, user decision strategies linked to ART predictions, evaluation of validity and reliability of ART, exploring the possibilities for incorporating the dermal route and integration of ART predictions with tools for modelling internal dose. ART is initially developed in the scope of REACH but is equally useful for exposure assessment in other areas. PMID- 22080163 TI - A fishnet electrochemical Hg2+ sensing strategy based on gold nanoparticle bioconjugate and thymine-Hg(2+)-thymine coordination chemistry. AB - A novel electrochemical biosensing strategy based on a three-dimensional fishnet of DNA-linked nanoparticle supramolecular structure triggered by the analyst for detection of Hg(2+) has been designed. The detection limit is 7.38 pM and the sensor's selectivity and facility have been significantly improved. PMID- 22080164 TI - Inhibition of checkpoint kinase 1 abrogates G2/M checkpoint activation and promotes apoptosis under heat stress. AB - Hyperthermia induced by heat stress (HS) inhibits the proliferation of cancer cells and induces their apoptosis. However, the mechanism underlying HS-induced apoptosis remains elusive. Here, we demonstrated a novel evidence that checkpoint kinase 1 (Chk1) plays crucial roles in the apoptosis and regulation of cell cycle progression in cells under HS. In human leukemia Jurkat cells, interestingly, the ataxia telangiectasia and Rad-3 related (ATR)-Chk1 pathway was preferentially activated rather than the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (Chk2) pathway under HS. The selective inhibitors of ATR or Chk1 abrogated HS induced apoptosis in human leukemia Jurkat cells whereas the inhibition of ATM or Chk2 caused only marginal effects. Inhibition of ATR and Chk1 also abrogated G2/M checkpoint activation by HS in Jurkat cells. The effects of small interfering RNA targeting Chk1 were similar to those of the selective inhibitor of Chk1. In addition, the efficiencies of Chk1 inhibition on G2/M checkpoint abrogation and apoptosis induction were confirmed in the adherent cancer cell lines HeLa, HSC3, and PC3, suggesting that the targeting of Chk1 can be effective in solid tumors cells. In conclusion, these findings indicate a novel molecular basis of G2/M checkpoint activation and apoptosis in cells exposed to HS. PMID- 22080165 TI - Prognostic factors of visual field improvement after trans-sphenoidal approach for pituitary macroadenomas: review of the literature and analysis by quantitative method. AB - The objective of the study was to evaluate the preoperative visual field defect, the postoperative outcome and the possible prognostic factors in patients with pituitary macroadenoma, using a quantitative method (the mean deviation = MD), and to review the literature. A total of 73 patients, operated trough trans sphenoidal approach, were selected, and data in single eyes were analysed by calculating the frequency and the degree of postoperative improvement (relative improvement). The visual field defect improved in 95.7% of eyes: The recovery was complete in 48.9% and partial in 46.8%. Multivariate logistic regression showed that factors, independently predictive for complete recovery, were as follows: low preoperative MD absolute value (p = 0.008), low cranio-caudal diameter of tumour (p = 0.02) and young age (p = 0.0001). The mean relative improvement in visual field defect (dMD%) was correlated with the preoperative visual acuity (p = 0.0001) and inversely related with the preoperative MD (p = 0.007) and the age (p = 0.017). The relative improvement was higher in tumours with a smaller cranio caudal diameter (p = 0.0185). In conclusion, using a quantitative method, we can measure the degree of the postoperative visual field defect improvement. Predictive factors for a complete recovery were good preoperative visual function, young age and low cranio-caudal tumour. PMID- 22080166 TI - Vitamin K(2) improves renal function and increases femoral bone strength in rats with renal insufficiency. AB - Renal insufficiency induces cortical bone loss in rats. The present study examined the influence of vitamin K(2) on renal function, cortical bone mass, and bone strength in rats with renal insufficiency. Thirty male Sprague-Dawley rats (8 weeks old) were randomized by the stratified weight method to the following three groups of 10 animals each: sham operation (control), 5/6 nephrectomy, and 5/6 nephrectomy + oral vitamin K(2) (menaquinone-4, menatetrenone, 30 mg/kg, 5 days/week). Treatment was initiated 10 days after surgery. After 6 weeks of treatment, samples of serum, urine, and bone (femur and tibia) were obtained. Renal function was evaluated, bone histomorphometric analysis was performed on the tibial diaphysis, and the bone mineral density (BMD) and mechanical strength of the femoral diaphysis were determined by peripheral quantitative computed tomography and a three-point bending test, respectively. Nephrectomy induced renal dysfunction, as indicated by increased levels of serum creatinine and urea nitrogen along with a decrease of creatinine clearance; and it also decreased BMD without significantly affecting bone strength at the femoral diaphysis. Vitamin K(2) improved renal function parameters but did not significantly influence BMD at the femoral diaphysis. However, vitamin K(2) decreased the bone marrow area of the tibial diaphysis and increased the stiffness of the femoral diaphysis. These findings suggest that administration of vitamin K(2) improves renal function and increases cortical bone strength without altering BMD in rats with renal insufficiency. PMID- 22080167 TI - Biased attention towards negative schematic expression in abstinent heroin abusers. AB - BACKGROUND AND OBJECTIVES: Drug dependents exhibit biases when evaluating emotional facial expressions; however little is known about their emotional biases appearing at the pre-awareness stage. The present study examined whether abstinent heroin abusers preferentially attended to facial expressions with particular emotion type. METHOD: Thirty-seven abstinent heroin abusers (AH participants), twenty normal healthy controls (NC participants), and nineteen individuals with moderate anxiety/depression disorders (PC participants) were included in the study. Participants searched displays containing a varying number of schematic neutral faces for a unique schematic face expressing either a positive or a negative emotion. RESULTS: Results revealed that AH participants had generally shallower search slopes for locating the negative target face than those for locating the positive one, whereas no such difference was found on NC participants or PC participants. CONCLUSION: It suggested that abstinent heroin abusers are biased to attend to negative expression more effectively than attend to positive expression. We proposed that this may result from abstinent heroin abusers' repeated exposure to people's negative expressions in their living environment or a pre-existing emotional processing deficit which could initiate the development of drug abuse behaviour. PMID- 22080168 TI - A novel multi-targeted tyrosine kinase inhibitor, linifanib (ABT-869), produces functional and structural changes in tumor vasculature in an orthotopic rat glioma model. AB - Tyrosine kinase inhibitors represent a class of targeted therapy that has proven to be successful for cancer treatment. Linifanib is a novel, orally active multi targeted receptor tyrosine kinase (RTK) inhibitor that exhibits potent antitumor and antiangiogenic activities against a broad spectrum of experimental tumors and malignancies in patients. The compound is currently being evaluated in phase 2 and 3 clinical trials. To investigate the effectiveness of linifinib against gliomas and the mechanism of drug action, we characterized treatment-induced antitumor and antiangiogenic responses to linifanib in an orthotopic rat glioma model. The effect of linifanib treatment on tumor growth was determined by tumor volume assessment using anatomical magnetic resonance imaging (MRI). Changes in tumor microvessel function were evaluated with dynamic contrast-enhanced MRI (DCE MRI). Immunohistochemistry (IHC) was applied to excised tumor samples to examine underlying changes in vascular structures and target receptor expression. Linifanib (10 mg/kg) given twice daily inhibited tumor growth following treatment for 7 days with tumor volumes being 149 +/- 30 and 66 +/- 7 mm(3) for vehicle-and linifanib-treated groups, respectively. A significant reduction of 37 +/- 13% in tumor perfusion and microvessel permeability (measured by K (trans)) was observed as early as 2 h after administration compared with vehicle treatment. Continuous linifanib administration further reduced K (trans) at later time points until the end of the study (7 days post-treatment). At day 7, K (trans) was reduced by 75 +/- 32% for linifanib treatment compared with vehicle treatment. Significant reduction in total blood vessel density and improved vessel wall integrity were observed, and staining for target receptor expression confirmed inhibition of phospho VEGFR-2 and PDGFR-beta by linifanib treatment. These results demonstrate significant antitumor and antiangiogenic activity against gliomas by linifanib, a property that may result from the inhibition of VEGFR-2 and PDGFR-beta-mediated vascular changes. DCE-MRI measured K (trans) changes at early treatment stages may be a useful pharmacodynamic marker for linifanib activity in clinical trials, and basal K (trans) may provide predictive value for tumor progression. PMID- 22080169 TI - Chidamide (CS055/HBI-8000): a new histone deacetylase inhibitor of the benzamide class with antitumor activity and the ability to enhance immune cell-mediated tumor cell cytotoxicity. AB - PURPOSE: Chidamide (CS055/HBI-8000) is a new histone deacetylase (HDAC) inhibitor of the benzamide class currently under clinical development in cancer indications. This study reports the in vitro and in vivo antitumor characteristics of the compound. METHODS: Selectivity and potency of chidamide in inhibition of HDAC isotypes were analyzed by using a panel of human recombinant HDAC proteins. Tumor cell lines either in culture or inoculated in nude mice were used for the evaluation of the compound's antitumor activity. To investigate the immune cell-mediated antitumor effect, isolated peripheral blood mononuclear cells from healthy donors were treated with chidamide, and cytotoxicity and expression of relevant surface proteins were analyzed. Microarray gene expression studies were performed on peripheral white blood cells from two T-cell lymphoma patients treated with chidamide. RESULTS: Chidamide was found to be a low nanomolar inhibitor of HDAC1, 2, 3, and 10, the HDAC isotypes well documented to be associated with the malignant phenotype. Significant and broad spectrum in vitro and in vivo antitumor activity, including a wide therapeutic index, was observed. Chidamide was also shown to enhance the cytotoxic effect of human peripheral mononuclear cells ex vivo on K562 target cells, accompanied by the upregulation of proteins involved in NK cell functions. Furthermore, the expression of a number of genes involved in immune cell-mediated antitumor activity was observed to be upregulated in peripheral white blood cells from two T-cell lymphoma patients who responded to chidamide administration. CONCLUSIONS: The results presented in this study provide evidence that chidamide has potential applicability for the treatment of a variety of tumor types, either as a single agent or in combination therapies. PMID- 22080170 TI - Exposure to antiretroviral agents during pregnancy does not alter bone status in infants. AB - The use of combined antiretroviral agents during pregnancy is important to prevent mother-to-child transmission of human immunodeficiency virus (HIV). Antiretroviral treatment (ARV) is associated with reduced bone mass and altered bone metabolism in HIV-infected patients. There are no data regarding the effect of ARV exposure during pregnancy on newborns and infants. We therefore studied 38 subjects born from HIV-infected mothers, and we measured the speed-of-sound (SOS) at the tibia by quantitative ultrasonography (QUS) just after birth. QUS measurements at mid-tibia is easily performed in infants with the appropriate probe. Nevertheless, at this skeletal site only cortical bone is present, and therefore QUS measurements reflect the status of only one kind of bone tissue. We also measured bone alkaline phosphatase (BAP) and C-terminal telopeptide of type I collagen (CTX) in the cord blood as bone formation and resorption markers, respectively. SOS measurements were repeated at 4 and 12 months of age. As a control group we studied 94 subjects born from HIV-negative mothers. At birth the median (range) SOS of ARV-exposed neonates was 3006 (2870-3168) m/s, while that of control subjects was 3007 (2757-3311) m/s. The difference was not significant. BAP concentration of ARV-exposed was 103.6 (31.6-182.8) U/L, not different from that of control subjects (104.4 [43.2-227.2] U/L). CTX concentrations were 1.07 (0.26-2.8) ng/mL, and 1.38 (0.34-4.2) ng/mL in ARV-exposed and control subjects, respectively. SOS measurements at 4 months and 12 months of age were available for 17 ARV-exposed subjects and for 57 control subjects. SOS values changed significantly over time in both groups (F=6.1; P<0.0001). No differences were present between ARV-exposed and control subjects at 4 and 12 months. Our study suggests that ARV exposure during intrauterine life does not affect negatively bone metabolism and bone development, and that the changes occurring in bone QUS measurements during the first year of life in ARV-exposed subjects are similar to those occurring in healthy control infants. PMID- 22080171 TI - Poisoning effect diminished on a novel PdHoOx/C catalyst for the electrooxidation of formic acid. AB - A surprisingly high and stable current was observed after the peak current on the PdHoOx/C catalyst indicating the diminished poisoning effect. Moreover, the novel PdHoOx/C catalyst exhibited excellent catalytic activity and stability for formic acid oxidation due to the large electrochemical surface area and electronic effect. PMID- 22080172 TI - Lack of association between childhood immunizations and encephalitis in California, 1998-2008. AB - OBJECTIVE: A number of new and combination vaccines have been introduced for children in the past two decades. Encephalitis cases occurring within defined time windows following administration of pertussis- or measles-containing vaccines are eligible for compensation by the Vaccine Injury Compensation Program. Due to increased parental concerns about vaccine safety and potential neurologic adverse events following immunization with new and multiple vaccines administered at the same visit, our aim was to determine whether immunizations are associated with an increased risk of encephalitis within defined risk windows. METHODS: We reviewed immunization records from 246 pediatric encephalitis cases referred to the California Encephalitis Project between July 1998 and December 2008. We included data on 110 cases who had been immunized in the year prior to the onset of encephalitis (observation period) and had complete immunization records. We used the case-centered method to test whether cases were more likely to have developed encephalitis in defined risk windows-42, 30 and 21 days after any vaccination, 3 days after pertussis-containing vaccines and 5-15 days after measles-virus containing vaccines-compared with the rest of the observation period. RESULTS: All vaccines recommended in the current immunization schedule were represented in our sample. No increased risk of encephalitis was seen following administration of pertussis-containing vaccines, measles containing vaccines or any number of vaccines administered in a single visit (vaccine episode); the odds ratios and 95% confidence intervals for encephalitis after a vaccine episode were: 1.0 (0.6-1.8) in a 42-day risk window, 0.9 (0.5 1.6) in a 30-day risk window and 1.2 (0.7-2.2) in a 21-day risk window. CONCLUSION: No association between receipt of currently recommended immunizations and subsequent development of encephalitis was observed in this study. PMID- 22080173 TI - Vaccine-specific antibody secreting cells are a robust early marker of LAIV induced B-cell response in ferrets. AB - Currently, a robust set of immune correlates for live attenuated influenza vaccine (LAIV) efficacy in humans has not been fully elucidated. The serum hemagglutination inhibition (HAI) assay has been historically used to measure humoral immune responses to injectable inactivated influenza vaccination. However, serum antibody titers do not reliably reflect the complete mechanism of action of LAIV, which is an intranasally delivered vaccine and is expected to induce local mucosal and cellular immune responses in addition to humoral immune responses. Therefore, we designed a study to evaluate potential immune correlates of LAIV vaccination in the ferret animal model of influenza infection. Ferrets were vaccinated with increasing doses of LAIV and four weeks later challenged with a homologous wild-type (wt) H1N1 strain. Humoral immune responses measured following LAIV vaccination included HAI, serum antibodies and antibody secreting cells (ASC); and the responses were found to correlate with the dose level of LAIV administered in this model. Protection from wt virus challenge was determined by measuring inhibition of wt viral replication in nasal washes and in lung tissue. Results demonstrated that LAIV doses >= 5.0 log(10) Plaque Forming Units (PFU) elicited vaccine-specific IgG and IgA ASC frequencies and induced complete protection in the lungs. Further, we developed a novel model utilizing seropositive older ferrets to demonstrate that in the background of previous wt influenza infection LAIV induces a robust vaccine-specific B-cell response even in the absence of serum antibody response, a result that suggests that effector B cell responses generated by LAIV are not inhibited by prior viral exposure. Finally, we demonstrated that LAIV elicits strain-specific memory B-cell responses that are measurable in a background of wt influenza infections. Taken together, results from these studies identified the antigen-specific ASC frequency as a useful early biomarker of LAIV-induced B-cell immune response. PMID- 22080174 TI - Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine. AB - A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naive subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N=110) were randomized 1:1 to receive two vaccinations with either 3.75 MUg or 7.5 MUg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14% which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre >= 1:20) against the vaccine strain A/Indonesia/05/2005: 82.7% and 86.5% in the 3.75 MUg and 7.5 MUg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40% and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5 MUg dose group determined by SRH was only marginally lower (69.2%) than the CPMP criterion of >70%. Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21% by MN and >= 25% by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were reported. The H5N1 influenza vaccine against clade 2.1 strain A/Indonesia/05/2005 was well tolerated and immunogenic after two vaccinations, and induced a cross-neutralizing antibody response, with no dose effect. PMID- 22080175 TI - Pre-vaccination prevalence and distribution of high-risk human papillomavirus (HPV) types in Slovenian women: a cervical cancer screening based study. AB - To estimate the pre-vaccination prevalence of cervical infections with 14 high risk human papillomavirus (hr-HPV) types among 20-64 years old Slovenian women screened for cervical cancer in 2010, we consecutively enrolled 4431 women in 16 outpatient gynaecology services. All were screened with Digene Hybrid Capture 2 HPV DNA Test and Abbott Real Time High Risk HPV Test and all positive specimens genotyped. Prevalence of cervical infection with any hr-HPV type examined was 12.9% with HPV16 3.5% and with HPV18 1.0%. Age specific prevalence estimates were the highest among 20-24 years old women and decreased with age. HPV16 prevalence was lowest among women without evidence of cervical disease and increased with the severity to 41.9% in women with high grade squamous intraepithelial lesion. Our results provide baseline data for monitoring the impact of Slovenian HPV vaccination program and development of future cervical cancer screening strategies in cohorts eligible for free HPV vaccination. PMID- 22080176 TI - A parallel algorithm for reverse engineering of biological networks. AB - Dynamic biological systems, such as gene regulatory networks (GRNs) and protein signaling networks, are often represented as systems of ordinary differential equations. Such equations can be utilized in reverse engineering these biological networks, specifically since identifying these networks is challenging due to the cost of the necessary experiments growing with at least the square of the size of the system. Moreover, the number of possible models, proportional to the number of directed graphs connecting nodes representing the variables in the system, suffers from combinatorial explosion as the size of the system grows. Therefore, exhaustive searches for systems of nontrivial complexity are not feasible. Here we describe a practical and scalable algorithm for determining candidate network interactions based on decomposing an N-dimensional system into N one-dimensional problems. The algorithm was tested on in silico networks based on known biological GRNs. The computational complexity of the network identification is shown to increase as N(2) while a parallel implementation achieves essentially linear speedup with the increasing number of processing cores. For each in silico network tested, the algorithm successfully predicts a candidate network that reproduces the network dynamics. This approach dramatically reduces the computational demand required for reverse engineering GRNs and produces a wealth of exploitable information in the process. Moreover, the candidate network topologies returned by the algorithm can be used to design future experiments aimed at gathering informative data capable of further resolving the true network topology. PMID- 22080177 TI - Intra- and inter-cortical motor excitability in Alzheimer's disease. AB - Transcranial magnetic stimulation (TMS) provides evidence for facilitatory and inhibitory motor dysfunctions in Alzheimer's disease (AD). The corpus callosum (CC) is affected in AD already at early stages consistent with the hypothesis that AD patients exhibit alterations in transcallosally mediated motor inhibition (ipsilateral silent period, iSP). Therefore, here we aimed at investigating the integrity not only of intra-, but also of inter-hemispheric mechanisms of cortical motor excitability in AD. We determined the iSP, the resting motor threshold (RMT), and the amplitude of motor evoked potentials (MEP) in 19 AD patients and 19 healthy controls using single-pulse TMS. Furthermore, we used paired-pulse TMS to study the intra-cortical inhibition (ICI) and intra-cortical facilitation (ICF). All subjects underwent comprehensive neuropsychologic, clinical, and laboratory testing, and neuroimaging to exclude significant co morbidity. In AD patients, the RMT was significantly reduced (Oneway-ANOVA). An analysis of covariance (ANCOVA) revealed a strong group specific interaction of the inhibitory interstimulus intervals (p = 0.005) with a reduced ICI in AD. Furthermore, we found a significantly prolonged iSP-latency (p = 0.003) in AD compared to controls, whereas the iSP-duration was not different. The iSP-latency correlated significantly with the ICI (ANCOVA) (p = 0.02). The ICF did not differ significantly between groups. Our data suggest comprehensive but still subclinical dysfunctions of motor cortical inhibition in mild to moderate clinical stages of AD with strong interactions of intra- and inter-hemispheric inhibitory phenomena. Future studies are needed to show the potential prognostic relevance of these findings for the further course of the disease. PMID- 22080181 TI - Mapping local electric fields in proteins at biomimetic interfaces. AB - We present a novel approach for determining the strength of the electric field experienced by proteins immobilised on membrane models. It is based on the vibrational Stark effect of a nitrile label introduced at different positions on engineered proteins and monitored by surface enhanced infrared absorption spectroscopy. PMID- 22080182 TI - Exposed or not exposed? Exploring exposure classification in studies using administrative data to investigate outcomes following medication use during pregnancy. AB - PURPOSE: The aim of this systematic review was to examine and compare differences in the way medication exposures are classified in studies using linked administrative data to investigate outcomes following medication use during pregnancy. This was undertaken with a focus on studies investigating specific neonatal outcomes following prenatal exposure to selective serotonin reuptake inhibitors (SSRIs). METHODS: We searched Medline and Embase to identify studies that used linked administrative data to investigate specific neonatal outcomes (congenital malformations, birth weight, gestational age) following prenatal exposure to SSRIs. RESULTS: Key factors such as dose, duration and timing of exposure were inconsistently addressed in the studies identified. In addition, there was a great deal of variability in the way medication exposures were classified and how women who stop taking their medication before or during early pregnancy are handled in analyses. Furthermore, there are issues in assuming how and when women who receive a dispensing for a medication actually take it during pregnancy. This creates a great deal of uncertainty around medication exposure during pregnancy in studies using linked administrative data, potentially resulting in biased risk estimates. CONCLUSIONS: There is a need for greater focus on determining the most effective and accurate way of using linked administrative data to investigate outcomes following medication use during pregnancy in an effort to minimise potential biases. PMID- 22080183 TI - Perforated giant sigmoid diverticulum. PMID- 22080184 TI - A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) and c-kit are highly expressed in adenoid cystic carcinoma (ACC) and associated with biologic aggressiveness. This study aimed to assess the antitumor activity of sunitinib, a multi-targeted inhibitor of vascular endothelial growth factor receptor, c-kit, platelet-derived growth factor receptor, ret proto-oncogene (RET) and FMS-like tyrosine kinase 3 (FLT3), in ACC of the salivary gland. PATIENTS AND METHODS: Patients with progressive, recurrent and/or metastatic ACC were treated with sunitinib 37.5 mg daily in this single-arm, two-stage phase II trial. Response was assessed every 8 weeks. RESULTS: Fourteen patients were enrolled on to the study. Among 13 assessable patients, there were no objective responses, 11 patients had stable disease (SD), 8 patients had SD >= 6 months and 2 patients had progressive disease as best response. Median time to progression was 7.2 months. Median overall survival was 18.7 months. Toxic effects occurring in at least 50% of patients included fatigue, oral mucositis and hypophosphatemia usually of mild to moderate severity. CONCLUSIONS: Although no responses were observed, sunitinib was well tolerated, with prolonged tumor stabilization of >= 6 months in 62% of assessable patients. The lack of responses is comparable with other trials of molecularly targeted agents in ACC and highlights the need for novel strategies in phase II clinical trial design. PMID- 22080186 TI - Perspectives of relativistic quantum chemistry: the negative energy cat smiles. AB - Given the remarkable advances in relativistic quantum chemistry, some conceptual aspects still remain to be addressed. Among others, the role of negative energy states (NES) in electron correlation and other properties requires most attention. Based on critical assessments of the configuration space (CS), no photon (and no-time) Fock space (FS) and quantum electrodynamics (QED) approaches, it is concluded that only QED provides the correct prescription for the contributions of NES to correlation, while both CS and FS give rise to wrong results. This essentially means that one should work either with the no-pair approximation (which has an intrinsic error of order (Zalpha)(3)) or with QED. Whether a consistent relativistic many-electron theory does exist in between remains an open question. Even under the no-pair approximation, there still exists an issue arising from that the no-pair Hamiltonian is incompatible with explicitly correlated methods. It turns out that this can nicely be resolved by introducing the concept of extended no-pair projection. Apart from these take home messages, other immediate prospects of relativistic quantum chemistry are also highlighted for guiding future developments and applications. PMID- 22080187 TI - Uncovering toxicological complexity by multi-dimensional screenings in microsegmented flow: modulation of antibiotic interference by nanoparticles. AB - The technique of microsegmented flow was applied for the generation of two- and higher dimensional concentration spaces for the screening of toxic effects of selected substances on the bacterium Escherichia coli at the nanolitre scale. Up to about 5000 distinct experiments with different combinations of effector concentrations could be realized in a single experimental run. This was done with the help of a computer program controlling the flow rates of effector-containing syringe pumps and resulted in the formation of multi-dimensional concentration spaces in segment sequences. Prior to the application of this technique for toxicological studies on E. coli the accuracy of this method was tested by simulation experiments with up to five dissolved dyes with different spectral properties. Photometric microflow-through measurement of dye distribution inside the concentration spaces allowed the monitoring of microfluid segment compositions. Finally, we used this technique for the investigation of interferences of the antibiotics ampicillin and chloramphenicol towards E. coli cultures and their modulation by silver nanoparticles by measuring bacterial autofluorescence. Each concentration point in this three-dimensional concentration space was represented by 4 or 5 single segments. Thus, a high reliability of the measured dose/response relations was achieved. As a result, a complex response pattern was discovered including synergistic and compensatory effects as well as the modulation of the range of stimulation of bacterial growth by a sublethal dose of chloramphenicol by silver nanoparticles. PMID- 22080188 TI - Analysis of the tomato mild mottle virus genome indicates that it is the most divergent member of the genus Ipomovirus (family Potyviridae). AB - The complete genome of a tomato mild mottle virus (ToMMV) isolate was analysed, and some biological features were characterized. The ssRNA genome of ToMMV from Ethiopia encompasses 9283 nucleotides (excluding the 3' poly(A) tail) and encodes a polyprotein of 3011 amino acids. Phylogenetic and pairwise comparisons with other members of the family Potyviridae revealed that ToMMV is the most divergent member of the genus Ipomovirus, with a genome organization similar to that of members of the species Sweet potato mild mottle virus, the type species of the genus. In contrast to earlier reports, ToMMV isolates from Yemen and Ethiopia were not transmitted by the aphid Myzus persicae, but they were transmitted very erratically by the whitefly Bemisia tabaci. A comparison of the 3'-proximal sequences of different isolates provided evidence for geographically associated genetic variation. PMID- 22080189 TI - Effects of early developmental conditions on innate immunity are only evident under favourable adult conditions in zebra finches. AB - Long-term effects of unfavourable conditions during development can be expected to depend on the quality of the environment experienced by the same individuals during adulthood. Yet, in the majority of studies, long-term effects of early developmental conditions have been assessed under favourable adult conditions only. The immune system might be particularly vulnerable to early environmental conditions as its development, maintenance and use are thought to be energetically costly. Here, we studied the interactive effects of favourable and unfavourable conditions during nestling and adult stages on innate immunity (lysis and agglutination scores) of captive male and female zebra finches (Taeniopygia guttata). Nestling environmental conditions were manipulated by a brood size experiment, while a foraging cost treatment was imposed on the same individuals during adulthood. This combined treatment showed that innate immunity of adult zebra finches is affected by their early developmental conditions and varies between both sexes. Lysis scores, but not agglutination scores, were higher in individuals raised in small broods and in males. However, these effects were only present in birds that experienced low foraging costs. This study shows that the quality of the adult environment may shape the long-term consequences of early developmental conditions on innate immunity, as long-term effects of nestling environment were only evident under favourable adult conditions. PMID- 22080190 TI - Highly enantioselective Friedel-Crafts alkylation reaction catalyzed by rosin derived tertiary amine-thiourea: synthesis of modified chromanes with anticancer potency. AB - We present herein for the first time the synthesis and preliminary biological evaluation of various modified chromanes via a rosin-derived tertiary amine thiourea-catalyzed highly enantioselective Friedel-Crafts alkylation reaction. PMID- 22080185 TI - Neutrophils in innate host defense against Staphylococcus aureus infections. AB - Staphylococcus aureus has been an important human pathogen throughout history and is currently a leading cause of bacterial infections worldwide. S. aureus has the unique ability to cause a continuum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. Moreover, the emergence of highly virulent, drug-resistant strains such as methicillin-resistant S. aureus in both healthcare and community settings is a major therapeutic concern. Neutrophils are the most prominent cellular component of the innate immune system and provide an essential primary defense against bacterial pathogens such as S. aureus. Neutrophils are rapidly recruited to sites of infection where they bind and ingest invading S. aureus, and this process triggers potent oxidative and non oxidative antimicrobial killing mechanisms that serve to limit pathogen survival and dissemination. S. aureus has evolved numerous mechanisms to evade host defense strategies employed by neutrophils, including the ability to modulate normal neutrophil turnover, a process critical to the resolution of acute inflammation. Here we provide an overview of the role of neutrophils in host defense against bacterial pathogens and discuss strategies employed by S. aureus to circumvent neutrophil function. PMID- 22080191 TI - Transition metal abnormalities in progressive dementias. AB - Abnormal distributions of transition metals inside the brain are potential diagnostic markers for several central nervous system diseases, including Alzheimer's disease (AD), Parkinson's disease, dementia with Lewy bodies (DLB), bipolar disorders and depression. To further explore this possibility, the total concentrations of iron, zinc, copper, manganese, aluminum, chromium and cadmium were measured in post-mortem hippocampus and amygdala tissues taken from AD, DLB and Control patients. A statistically significant near fifty percent reduction in the total copper levels of AD patients was observed in both the hippocampus and amygdala. The statistical power of the hippocampus and amygdala copper analysis was found to be 86 and 74% respectively. No statistically significant deviations in the total metal concentrations were found for zinc, manganese, chromium or aluminum. Iron was found to be increased by 38% in AD amygdala tissues, but was unchanged in AD hippocampus tissues. Accounting for differences in tissue water content, as a function of both tissue type and disease state, revealed more consistencies with previous literature. To aid in the design of future experiments, the effect sizes for all tissue types and metals studied are also presented. PMID- 22080192 TI - Urosepsis caused by Globicatella sanguinis and Corynebacterium riegelii in an adult: case report and literature review. AB - We report an extremely rare case of urosepsis caused by Globicatella sanguinis and Corynebacterium riegelii coinfection in a 94-year-old Japanese man with nephrolithiasis. Prompt identification of this coinfection is important so that effective antimicrobial coverage can be initiated. PMID- 22080193 TI - Complementation of the exoS gene in the pvdE pyoverdine synthesis gene-deficient mutant of Pseudomonas aeruginosa results in recovery of the pvdE gene-mediated penetration through the intestinal epithelial cell barrier but not the pvdE mediated virulence in silkworms. AB - Translocation of endogenous Pseudomonas aeruginosa from the colonized intestinal tract is an important pathogenic phenomenon. Comparative genome hybridization analysis of high virulent and low virulent strains allowed us to identify bacterial genes that are associated with bacterial translocation from gut in infected hosts. Here we focused on the pvdE pyoverdine synthesis gene among the identified bacterial genes, showing that the pvdE gene is required for bacterial penetration through epithelial cell monolayers and for bacterial translocation from gut to hemolymph in infected silkworms. We next revealed that mRNA expression level of the exoS gene in a pvdE-deficient mutant (DeltapvdE) after incubation with Caco-2 cells was greatly reduced as compared with that in the wild-type strain. The pvdE- and exoS-complemented DeltapvdE strains (DeltapvdE/pvdE and DeltapvdE/exoS) showed recovery of the ability of bacterial penetration through Caco-2 cell monolayers and of the ability of bacterial translocation from gut to hemolymph in infected silkworms. However, there were differences between the ability of DeltapvdE/pvdE and DeltapvdE/exoS to kill silkworms after intestinal infection and to replicate in hemolymph following direct injection into the hemolymph: DeltapvdE/pvdE could kill silkworms after intestinal infection and could replicate in hemolymph to levels similar to those of the wild-type strain, but DeltapvdE/exoS could not. Taken together, our results suggest that the virulence of the wild-strain mediated by the pvdE gene is the result of the ability to both penetrate through the intestinal epithelial cell barrier depending on ExoS and to replicate in hemolymph independently of ExoS. PMID- 22080195 TI - Coumarin derivatives for dye sensitized solar cells: a TD-DFT study. AB - Time dependent density functional theory (TD-DFT) calculations have been carried out to study the electronic structure and the optical properties of five coumarin based dyes: C343, NKX-2311, NKX-2586, NKX-2753 and NKX-2593. We have found out that the position and width of the first band in the electronic absorption spectra, the absorption threshold and the LUMO energy with respect to the conduction band edge are key parameters in order to establish some criteria that allow evaluating the efficiency of coumarin derivatives as sensitizers in Dye Sensitized Solar Cells (DSSC). Those criteria predict the efficiency ordering for the coumarin series in good agreement with the experimental evidence. Presumably, they might be used in the design of new efficient organic based DSSC. PMID- 22080196 TI - A prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients with stringent cessation criteria for adefovir. AB - Adefovir is usually applied for therapy of chronic hepatitis B (CHB), but its effectiveness after cessation is still unknown. This study was to evaluate the effectiveness of adefovir treatment with strict cessation criteria in hepatitis B e antigen (HBeAg)-negative patients and to identify potentially important factors. One hundred forty-five HBeAg-negative CHB patients who had received adefovir treatment for at least 24 months and for whom serum hepatitis B virus (HBV) DNA had remained undetectable for at least 18 months before cessation were included. They were followed up monthly during the first four months and at 3 month or 6-month intervals thereafter. Patients with >=10(4) copies of HBV DNA per mL were defined as relapsed. In total, 95 patients relapsed within the follow up time, and more than 93% relapsed within 12 months after adefovir cessation. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 53.8%, 61.4%, 65.5%, 65.5%, 65.5% and 65.5%, respectively. Age was the only factor associated with relapse, with lower relapse rates in younger patients shown by Cox regression analysis. HBsAg seroconversion occurred in 12 patients, and none of them relapsed during follow-up. The effectiveness of adefovir therapy does not persist in HBeAg-negative CHB patients, even when strict cessation criteria are applied, except for patients aged <= 25 years. HBsAg seroconversion is the ideal endpoint of adefovir treatment. PMID- 22080194 TI - Development of a vaccine against Staphylococcus aureus. AB - A vaccine to prevent infections caused by Staphylococcus aureus would have a tremendously beneficial impact on public health. In contrast to typical encapsulated bacterial pathogens, such as Streptococcus pneumoniae, H. influenzae, and Neisseria meningitides, the capsule of S. aureus is not clearly linked to strain virulence in vivo. Furthermore, it is not clear that natural infection caused by S. aureus induces a protective humoral immune response, as does infection caused by typical encapsulated bacteria. Finally, pure B cell or antibody deficiency, in either animal models or in patients, does not predispose to more frequent or more severe S. aureus infections, as it does for infections caused by typical encapsulated bacteria. Rather, primary immune mechanisms necessary for protection against S. aureus infections include professional phagocytes and T lymphocytes (Th17 cells, in particular) which upregulate phagocytic activity. Thus, it is not clear whether an antibody-mediated neutralization of S. aureus virulence factors should be the goal of vaccination. Rather, the selection of antigenic targets which induce potent T cell immune responses that react to the broadest possible array of S. aureus strains should be the focus of antigen selection. Of particular promise is the potential to select antigens which induce both humoral and T cell-mediated immunity in order to generate immune synergy against S. aureus infections. A single-antigen vaccine may achieve this immune synergy. However, multivalent antigens may be more likely to induce both humoral and T cell immunity and to induce protection against a broader array of S. aureus isolates. A number of candidate vaccines are in development, raising the promise that effective vaccines against S. aureus will become available in the not-so-distant future. Possible development programs for such vaccines are discussed. PMID- 22080197 TI - [Deep brain stimulation - expectations and doubts. A nationwide questionnaire study of patients with Parkinson's disease and their family members]. AB - BACKGROUND: The aim of this questionnaire-based study was to determine the decision-making motives from Parkinson's patients and their family members for deep brain stimulation (DBS), which are crucial for the attitude towards this therapy and which should be considered during the clinical interview. MATERIAL AND METHODS: The questionnaire was sent out nationwide to members of the German Parkinson Association. Patient and family specific data as well as information sources, doubts and expectations with respect to DBS were assessed. RESULTS: A total of 582 patients and 476 family members answered the questionnaire, revealing that 96% of the patients and 91% of the family members already possessed information regarding DBS. While a large proportion of interviewees had specific expectations concerning DBS, more than two thirds expressed concerns regarding DBS; the most frequent with respect to intraoperative complications and stimulation-induced worsening of symptoms. The quantity of realistic patients and family expectations significantly correlated with a positive evaluation of DBS and doubts as well as unrealistic expectations of family members correlated with a negative attitude towards the operation. CONCLUSIONS: The findings suggest that patients and their relatives organized in support groups indeed possess detailed information regarding DBS. However, for the acceptance of the treatment a timely elucidation about DBS as well as responding to the individual concerns by the consulting physician is essential. PMID- 22080198 TI - [Cannabinoids for symptomatic therapy of multiple sclerosis]. AB - Spasticity represents a common troublesome symptom in patients with multiple sclerosis (MS). Treatment of spasticity remains difficult, which has prompted some patients to self-medicate with and perceive benefits from cannabis. Advances in the understanding of cannabinoid biology support these anecdotal observations. Various clinical reports as well as randomized, double-blind, placebo-controlled studies have now demonstrated clinical efficacy of cannabinoids for the treatment of spasticity in MS patients. Sativex is a 1:1 mix of delta-9-tetrahydocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which recently received a label for treating MS-related spasticity in Germany. The present article reviews the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option in MS. PMID- 22080200 TI - Hexavalent chromium-induced erythrocyte membrane phospholipid asymmetry. AB - Hexavalent (VI) chromium is a global contaminant with cytotoxic activity. Chromium (VI) induces oxidative stress, inflammation, cell proliferation, malignant transformation and may trigger carcinogenesis and at the same time apoptosis. The toxic effects of chromium (VI) at least partially result from mitochondrial injury and DNA damage. Erythrocytes lack mitochondria and nuclei but may experience an apoptosis-like suicidal cell death, i.e. eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptosis may result from increase of cytosolic Ca(2+) activity, ATP depletion and/or ceramide formation. The present study explored, whether chromium (VI) triggers eryptosis. Fluo-3 fluorescence was employed to determine cytosolic Ca(2+)-concentration, forward scatter to estimate cell volume, binding of fluorescent annexin V to detect phosphatidylserine exposure, hemoglobin concentration in the supernatant to quantify hemolysis, luciferin-luciferase to determine cytosolic ATP concentration and fluorescent anti-ceramide antibodies to uncover ceramide formation. A 48 h exposure to chromium (VI) (>=10 MUM) significantly increased cytosolic Ca(2+) concentration, decreased ATP concentration (20 MUM), decreased forward scatter, increased annexin V-binding and increased (albeit to a much smaller extent) hemolysis. Chromium (VI) did not significantly modify ceramide formation. The effect of 20 MUM chromium (VI) on annexin V binding was partially reversed in the nominal absence of Ca(2+). The present observations disclose a novel effect of chromium (VI), i.e. Ca(2+) entry and cytosolic ATP depletion in erythrocytes, effects resulting in eryptosis with cell shrinkage and cell membrane scrambling. PMID- 22080199 TI - Cell-selective labeling of bacterial proteomes with an orthogonal phenylalanine amino acid reporter. AB - Orthogonal amino acid reporters allow the selective labeling of different cell types in heterogeneous populations through the expression of engineered aminoacyl tRNA synthetases. Here, we demonstrate that para-ethynylphenylalanine (PEP) can be used as an orthogonal amino acid reporter for efficient selective labeling of an intracellular bacterial pathogen during infection. PMID- 22080201 TI - Lack of ceruloplasmin expression alters aspects of copper transport to the fetus and newborn, as determined in mice. AB - Copper transport and accumulation were studied in virgin and lactating C57BL/6 mice, with and without expression of ceruloplasmin (Cp), to assess the importance of Cp to these processes. One hour after i.p. injection of tracer (64)Cu, liver and kidney accounted for 80% of the radioactivity, and mammary gland 1%, while in lactating Cp+/+ mice 2-4 days post partum, uptake by mammary gland was 9-fold higher and that of liver and other organs was decreased, with (64)Cu rapidly appearing in milk. Parallel studies in Cp-/- mice (siblings from same colony) gave virtually identical results. However, their milk contained less (64)Cu, and actual copper contents determined by furnace atomic absorption were less than half those for milk from normal dams. Liver copper concentrations of pups born to Cp-/- dams also were half those of pups from wild type dams. Copper in pup brains was unaffected; but iron concentrations were reduced. We conclude that absence of Cp, while not affecting entry of exchangeable copper from the blood into the mammary gland, does have a significant effect on the availability of this metal to the newborn through the milk and in the form of stores accumulating in gestation. PMID- 22080202 TI - Encephalopathy, disseminated intravascular coagulation, and hemolytic-uremic syndrome after infection with enterohemorrhagic Escherichia coli O111. AB - An outbreak of enterohemorrhagic Escherichia coli (EHEC) occurred in Toyama and other prefectures in Japan during 2011. Some patients, including adults, showed complications such as encephalopathy, disseminated intravascular coagulation, and hemolytic-uremic syndrome, and the disease course was extremely aggressive. This report describes the clinical features of four patients infected with Escherichia coli (E. coli) O111 who developed very severe to fatal complications. The initial symptoms in all patients included abdominal pain, diarrhea, and bloody stools, and neurological abnormalities started to appear from 1 to 3 days after admission. Vomiting and pyrexia developed in three patients. Leukocyte counts, lactate dehydrogenase (LDH), and fibrin/fibrinogen degradation products were elevated, and thrombocytopenia was evident. Extremely elevated LDH and severe thrombocytopenia were characteristic at the time encephalopathy became apparent. All patients received oral fosfomycin, intravenous antibiotics, and anticoagulant therapy, three received gamma globulin, plasma exchange, and blood transfusion, and two received steroids and dialysis. Three patients required mechanical ventilation, and two adult patients died. E. coli O111 positive for Shiga toxin 2 was detected in stool culture in two patients, and serological tests for E. coli O111 were positive in the other two patients. In conclusion, EHEC O111 can cause severe illness in children and adults, and the prognosis becomes poorer as the severity of complications increases. Close monitoring including platelet counts and LDH are useful. Once these clinical parameters change, intensive treatment should be provided to prevent the development of severe complications. PMID- 22080203 TI - Iliopsoas abscess caused by Aspergillus fumigatus complicated by pulmonary aspergillosis. AB - We report a case of iliopsoas abscess caused by Aspergillus fumigatus with pulmonary complications. A 60-year-old man was admitted to the Showa University Hospital Department of Gastroenterology with fulminant hepatitis B on April 14, 2010, and treated with steroids. Although fulminant hepatitis B was improved by steroid and symptomatic therapy, he developed a fever on hospital day 39. The chest X-ray film showed a nodular lesion in the right middle-lower lung field, and both the (1 -> 3)-beta-D: -glucan and Candida mannan antigen tests were positive. The beta-D: -glucan level increased despite treatment with fluconazole and other drugs, including low-dose micafungin. Abdominal computed tomography showed a low-density area in the right iliopsoas muscle. He was then referred to the Department of Clinical Infectious Diseases. A. fumigatus was isolated from the iliopsoas lesion and the pulmonary lesion after specimens were obtained by aspiration and bronchofiberscopy, respectively, leading to a diagnosis of fungal iliopsoas abscess. Steroid therapy was tapered early, the abscess was drained, and the micafungin dose was increased. This treatment led to improvement of the fever, inflammatory reaction, beta-D: -glucan level, and lesions of the lung and iliopsoas muscle. In preparation for discharge, treatment was changed to voriconazole (parenteral -> per oral) followed by itraconazole (per oral). His clinical course was satisfactory, and there was no recurrence after antifungal therapy was stopped. We conclude that after invasive pulmonary aspergillosis developed, A. fumigatus spread hematogenously to create an extremely rare iliopsoas abscess. The beta-D: -glucan level closely reflected the response to treatment and was useful for follow-up. PMID- 22080204 TI - Enhanced production of beta-carotene by recombinant industrial wine yeast using grape juice as substrate. AB - In this study, both recombinant Saccharomyces cerevisiae T73-63 and FY-09 derived from the industrial wine yeast T73-4 and laboratory yeast FY1679-01B, respectively, were constructed and compared for their beta-carotene production in real grape juice. The results showed that highest beta-carotene content (5.89 mg/g) was found in strain T73-63, which was 2.1 fold higher than that of strain FY-09. Although the cell growth was inhibited by the metabolic burden induced by the production of heterogeneous beta-carotene, the pigment yield in T73-63 was still 1.7 fold higher than that of FY-09. Furthermore, high contents of ergosterol and fatty acid were also observed in T73-63. These results suggest that industrial wine yeast has highly active metabolic flux in mevalonate pathway, which leads to more carbon flux into carotenoid branch compared to that of laboratory yeast. The results of this study collectively suggest that in the application of recombinant strains to produce carotenoid using agro-industrial by products as substrate, the suitable host strains should have active mevalonate pathway. For this purpose, the industrial wine yeast is a suitable candidate. PMID- 22080205 TI - 4-Component relativistic magnetically induced current density using London atomic orbitals. AB - We present the implementation and application of 4-component relativistic magnetically induced current density using London atomic orbitals for self consistent field models. We obtain a magnetically balanced basis by a simple scheme where orbitals obtained by imposing restricted kinetic balance are extended by their unrestricted kinetic balance complement. The presented methodology makes it possible to analyze the concept of aromaticity based on the ring current criterion for closed-shell molecules across the periodic table and is independent of the choice of gauge origin. As a first illustration of the methodology we study plots of the magnetically induced current density and its divergence in the series C(5)H(5)E (E = CH, N, P, As, Sb, Bi) at the Kohn-Sham level, as well as integrated ring current susceptibilities, which we compare to previous results (R. Bast et al., Chem. Phys., 2009, 356, 187) obtained using a common gauge origin approach. We find that the current strength decreases monotonically along the series, but that all molecules qualify as aromatic according to the ring current criterion. PMID- 22080207 TI - Role of polyamines, their analogs and transglutaminases in biological and clinical perspectives. PMID- 22080206 TI - Disease mutations in disordered regions--exception to the rule? AB - Intrinsically disordered proteins (IDPs) have been implicated in a number of human diseases, including cancer, diabetes, neurodegenerative and cardiovascular disorders. Although for some of these conditions molecular mechanisms are now better understood, the big picture connecting distinct structural properties and functional repertoire of IDPs to pathogenesis and disease progression is still incomplete. Recent studies suggest that signaling and regulatory roles carried out by IDPs require them to be tightly regulated, and that altered IDP abundance may lead to disease. Here, we propose another link between IDPs and disease that takes into account disease-associated missense mutations located in the intrinsically disordered regions. We argue that such mutations are more prevalent and have larger functional impact than previously thought. In addition, we demonstrate that deleterious amino acid substitutions that cause disorder-to order transitions are particularly enriched among disease mutations compared to neutral polymorphisms. Finally, we discuss potential differences in functional outcomes between disease mutations in ordered and disordered regions, and challenge the conventional structure-centric view of missense mutations. PMID- 22080208 TI - Chemically modified diamond-like carbon (DLC) for protein enrichment and profiling by MALDI-MS. AB - The development of new high throughput methods based on different materials with chemical modifications for protein profiling of complex mixtures leads towards biomarkers; used particularly for early diagnosis of a disease. In this work, diamond-like carbon (DLC) is developed and optimized for serum protein profiling by matrix-assisted laser/desorption ionization mass spectrometry (MALDI-MS). This study is carried out in connection with a material-based approach, termed as material-enhanced laser desorption ionization mass spectrometry. DLC is selected as carrier surface which provides large surface to volume ratio and offers high sensitivity. DLC has a dual role of working as MALDI target while acting as an interface for protein profiling by specifically binding peptides and proteins out of serum samples. Serum constituents are bound through immobilized metal ion affinity chromatography (IMAC) functionality, created through glycidyl methacrylate polymerization under ultraviolet light followed by further derivatization with iminodiacetic acid and copper ion loading. Scanning electron microscopy highlights the morphological characteristics of DLC surface. It could be demonstrated that IMAC functionalized DLC coatings represent a powerful material in trapping biomolecules for their further analysis by MALDI-MS resulting in improved sensitivity, specificity and capacity in comparison to other protein-profiling methods. PMID- 22080209 TI - Identification of human salivary transglutaminases. AB - Transglutaminases (TGs) expression and enzymatic activities in human saliva were investigated. Specific antibodies showed the co-existence of TG1, TG2, TG3 and TG4. TG2 and TG3 were found in native and multiple proteolytic forms. Our data indicate that TG1 and TG2 isoenzymes are highly active with the major activity attributed to TG1. These findings pave the way for future studies on the physiological role of TG in the oral cavity and the potential impact of their deregulation in TG-associated oral diseases. PMID- 22080211 TI - Sino-orbital osteoma with osteoblastoma-like features: case reports. AB - Most of the orbital osteomas arise from the adjacent paranasal sinuses. Some of them may contain osteoblastoma-like areas and may be misdiagnosed as osteoblastoma, both radiologically as well as histopathologically. Sino-orbital osteomas with osteoblastoma-like features show a typical radiological appearance. They have a distinct zonal pattern, in which less dense osteoblastoma-like areas are located at the base of the lesion and dense mature bone is located at the periphery. These broad-based bone lesions also have a tendency for extracavitary polypoid growths from the paranasal sinus into the adjacent orbit. We report here the CT and MR imaging findings of three cases with sino-orbital osteoma with osteoblastoma-like features. PMID- 22080210 TI - Electrophilic fluorination of cationic Pt-aryl complexes. AB - The electrophilic fluorination of several (triphos)Pt-aryl(+) establishes the first example of aryl-F coupling from a Pt center. PMID- 22080212 TI - Effects of dialysis on the pharmacokinetics of salazosulfapyridine. AB - There was no standard or report for the treatment of rheumatoid arthritis (RA) patients on hemodialysis with Salazosulfapyridine (SASP). We examined the pharmacokinetics of SASP and its metabolites in RA patient on hemodialysis. Hemodialysis was started 2 h after administration of SASP at a dose of 250 or 500 mg. Blood samples were took 8 times during the observation period. The concentration of SASP and its metabolites (SP, Ac-SP) in blood sample were measured. There was no difference for the concentration of SASP before and after hemodialysis. Results showed SASP was nondialyzable, but SP and AC-SP were dialyzable. At a dose of 500 mg, AUC0-infinity of SASP and SP were higher than healthy volunteer. Therapy with SASP for hemodialysis RA should be started at a lower dose for adverse event risk. PMID- 22080213 TI - The mathematical origins of the kinetic compensation effect: 1. The effect of random experimental errors. AB - The kinetic compensation effect states that there is a linear relationship between Arrhenius parameters ln A and E for a family of related processes. It is a widely observed phenomenon in many areas of science, notably heterogeneous catalysis. This paper explores one of the mathematical, rather than physicochemical, explanations for the compensation effect and for the isokinetic relationship. It is demonstrated, both theoretically and by numerical simulations, that random errors in kinetic data generate an apparent compensation effect (sometimes termed the statistical compensation effect) when the true Arrhenius parameters are constant. Expressions for the gradient of data points on a plot of ln A against E are derived when experimental kinetic data are analysed by linear regression, by non-linear regression and by weighted linear regression. It is shown that the most appropriate analysis technique depends critically on the error structure of the kinetic data. Whenever data points on a plot of ln A against E are in a straight line with a gradient close to 1/RT, then confidence ellipses should be calculated for each data point to investigate whether the apparent compensation effect arises from random errors in the kinetic measurements or has some other origin. PMID- 22080214 TI - Dynamic optimization of signal transduction via intrinsic disorder. AB - It is widely accepted that the inherent flexibility of intrinsically disordered proteins (IDPs) correlates with essential functions in the cell such as signaling. However, the mechanisms by which disorder dynamically facilitates and optimizes signal transduction remain unclear. In this study, we have used a computational protocol to evaluate the interplay between the intrinsic disorder of p27(kip1) and the collective motions of its binding partners, cyclin dependent kinase 2 (CDK2) and cyclin A (CA). We found that the synergy between intrinsic disorder of p27(kip1) and the essential collective motions of the CDK2-CA complex introduces a set of sequential steps to dynamically optimize signal transduction. Our observations indicate that optimized p27(kip1)-mediated signaling originates from a combination of adaptive folding, and the cooperativity between its residual disorder and the functional collective motions of the CDK2-CA complex. PMID- 22080215 TI - Beneficial effect of taurine on hypoxia- and glutamate-induced endoplasmic reticulum stress pathways in primary neuronal culture. AB - Stroke (hypoxia) is one of the leading causes of mortality in the developed countries, and it can induce excessive glutamate release and endoplasmic reticulum (ER) stress. Taurine, as a free amino acid, present in high concentrations in a range of organs in mammals, can provide protection against multiple neurological diseases. Here, we present a study to investigate the potential protective benefits of taurine against ER stress induced by glutamate and hypoxia/reoxygenation in primary cortical neuronal cultures. We found that taurine suppresses the up-regulation of caspase-12 and GADD153/CHOP induced by hypoxia/reoxygenation, suggesting that taurine may exert a protective function against hypoxia/reoxygenation by reducing the ER stress. Moreover, taurine can down-regulate the ratio of cleaved ATF6 and full length ATF6, and p-IRE1 expression, indicating that taurine inhibits the ER stress induced by hypoxia/reoxygenation and glutamate through suppressing ATF6 and IRE1 pathways. PMID- 22080216 TI - A simple screening method using ion chromatography for the diagnosis of cerebral creatine deficiency syndromes. AB - Cerebral creatine deficiency syndromes (CCDS) are caused by genetic defects in L arginine:glycine amidinotransferase, guanidinoacetate methyltransferase or creatine transporter 1. CCDS are characterized by abnormal concentrations of urinary creatine (CR), guanidinoacetic acid (GA), or creatinine (CN). In this study, we describe a simple HPLC method to determine the concentrations of CR, GA, and CN using a weak-acid ion chromatography column with a UV detector without any derivatization. CR, GA, and CN were separated clearly with the retention times (mean +/- SD, n = 3) of 5.54 +/- 0.0035 min for CR, 6.41 +/- 0.0079 min for GA, and 13.53 +/- 0.046 min for CN. This new method should provide a simple screening test for the diagnosis of CCDS. PMID- 22080217 TI - cDNA-AFLP-based genetical genomics in cotton fibers. AB - Genetical genomics, or genetic analysis applied to gene expression data, has not been widely used in plants. We used quantitative cDNA-AFLP to monitor the variation in the expression level of cotton fiber transcripts among a population of inter-specific Gossypium hirsutum * G. barbadense recombinant inbred lines (RILs). Two key fiber developmental stages, elongation (10 days post anthesis, dpa), and secondary cell wall thickening (22 dpa), were studied. Normalized intensity ratios of 3,263 and 1,201 transcript-derived fragments (TDFs) segregating over 88 RILs were analyzed for quantitative trait loci (QTL) mapping for the 10 and 22 dpa fibers, respectively. Two-thirds of all TDFs mapped between 1 and 6 eQTLs (LOD > 3.5). Chromosome 21 had a higher density of eQTLs than other chromosomes in both data sets and, within chromosomes, hotspots of presumably trans-acting eQTLs were identified. The eQTL hotspots were compared to the location of phenotypic QTLs for fiber characteristics among the RILs, and several cases of co-localization were detected. Quantitative RT-PCR for 15 sequenced TDFs showed that 3 TDFs had at least one eQTL at a similar location to those identified by cDNA-AFLP, while 3 other TDFs mapped an eQTL at a similar location but with opposite additive effect. In conclusion, cDNA-AFLP proved to be a cost effective and highly transferable platform for genome-wide and population-wide gene expression profiling. Because TDFs are anonymous, further validation and interpretation (in silico analysis, qPCR gene profiling) of the eQTL and eQTL hotspots will be facilitated by the increasing availability of cDNA and genomic sequence resources in cotton. PMID- 22080218 TI - Self-replication reactions dependent on tertiary interaction motifs in an RNA ligase ribozyme. AB - RNA can function both as an informational molecule and as a catalyst in living organisms. This duality is the premise of the RNA world hypothesis. However, one flaw in the hypothesis that RNA was the most essential molecule in primitive life is that no RNA self-replicating system has been found in nature. To verify whether RNA has the potential for self-replication, we constructed a new RNA self assembling ribozyme that could have conducted an evolvable RNA self-replication reaction. The artificially designed, in vitro selected ligase ribozyme was employed as a prototype for a self-assembling ribozyme. The ribozyme is composed of two RNA fragments (form R1.Z1) that recognize another R1.Z1 molecule as their substrate and perform the high turnover ligation reaction via two RNA tertiary interaction motifs. Furthermore, the substrate recognition of R1.Z1 is tolerant of mutations, generating diversity in the corresponding RNA self-replicating network. Thus, we propose that our system implies the significance of RNA tertiary motifs in the early RNA molecular evolution of the RNA world. PMID- 22080219 TI - Quantum dot/cyclodextrin supramolecular systems based on efficient molecular recognition and their use for sensing. AB - A supramolecular system based on ketoprofen functionalised CdSe/ZnS nanoparticles and pyrene-modified beta-CD was prepared and successfully used for molecular sensing of different analytes. In addition, a strategy for the individual recovery of all the components of the sensing assay is reported. PMID- 22080221 TI - Discriminating male and female voices: differentiating pitch and gender. AB - Gender is salient, socially critical information obtained from faces and voices, yet the brain processes underlying gender discrimination have not been well studied. We investigated neural correlates of gender processing of voices in two ERP studies. In the first, ERP differences were seen between female and male voices starting at 87 ms, in both spatial-temporal and peak analyses, particularly the fronto-central N1 and P2. As pitch differences may drive gender differences, the second study used normal, high- and low-pitch voices. The results of these studies suggested that differences in pitch produced early effects (27-63 ms). Gender effects were seen on N1 (120 ms) with implicit pitch processing (study 1), but were not seen with manipulations of pitch (study 2), demonstrating that N1 was modulated by attention. P2 (between 170 and 230 ms) discriminated male from female voices, independent of pitch. Thus, these data show that there are two stages in voice gender processing; a very early pitch or frequency discrimination and a later more accurate determination of gender at the P2 latency. PMID- 22080220 TI - Outcome of closed ipsilateral metacarpal fractures treated with mini fragment plates and screws: a prospective study. AB - BACKGROUND: Closed multiple metacarpal fractures are considered highly unstable and are more prone to poor functional outcome. The authors assess the functional outcome of mini fragment plate fixation in closed ipsilateral multiple metacarpal fractures. PATIENTS AND METHODS: In 21 patients with closed ipsilateral multiple metacarpal fractures treated with open reduction and internal fixation using mini fragment plate, functional outcome was assessed using the American Society for Surgery of the Hand (ASSH) Total Active Flexion (TAF) score and the Disabilities of the Arm, Shoulder, and Hand (DASH) scoring system. RESULTS: Union rate of 100% was achieved. Functional outcome was excellent in 85.71% (18 of 21) and good in 9% (2 of 21) of patients. Average DASH score was 8.47 (range 1-26). Five cases of infection (two deep, three superficial) were reported, which subsided with dressings and antibiotics. CONCLUSIONS: Plate fixation is a good option for treating closed ipsilateral multiple metacarpal fractures, providing rigid fixation for early mobilization and good functional outcome. PMID- 22080222 TI - Sensory handedness is not reflected in cortical responses after basic nerve stimulation: a MEG study. AB - Motor dominance is well established, but sensory dominance is much less clear. We therefore studied the cortical evoked magnetic fields using magnetoencephalography (MEG) in a group of 20 healthy right handed subjects in order to examine whether standard electrical stimulation of the median and ulnar nerve demonstrated sensory lateralization. The global field power (GFP) curves, as an indication of cortical activation, did not depict sensory lateralization to the dominant left hemisphere. Comparison of the M20, M30, and M70 peak latencies and GFP values exhibited no statistical differences between the hemispheres, indicating no sensory hemispherical dominance at these latencies for each nerve. Field maps at these latencies presented a first and second polarity reversal for both median and ulnar stimulation. Spatial dipole position parameters did not reveal statistical left-right differences at the M20, M30 and M70 peaks for both nerves. Neither did the dipolar strengths at M20, M30 and M70 show a statistical left-right difference for both nerves. Finally, the Laterality Indices of the M20, M30 and M70 strengths did not indicate complete lateralization to one of the hemispheres. After electrical median and ulnar nerve stimulation no evidence was found for sensory hand dominance in brain responses of either hand, as measured by MEG. The results can provide a new assessment of patients with sensory dysfunctions or perceptual distortion when sensory dominance occurs way beyond the estimated norm. PMID- 22080223 TI - Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study. AB - OBJECTIVE: Orthostatic hypotension has a prognostic role in determining cardiovascular and all-cause mortality. The aim of this study was to assess the prevalence of orthostatic hypotension and its association with blood pressure (BP) levels, arterial stiffness, cardiovascular and metabolic disorders and medication in individuals aged 80 years and over living in nursing home. METHODS: In 994 individuals (77% women, mean age 88+/-5 years), the presence of orthostatic hypotension was tested according to American Autonomic Society and American Academy of Neurology guidelines. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cf-PWV), peripheral to central pulse pressure amplification (PPA) and augmentation index. Cardiovascular and metabolic disorders as well as medications were recorded from patients' medical records. RESULTS: The prevalence of orthostatic hypotension was 18%. Treated hypertensive patients with SBP 140 mmHg or less had a lower prevalence of orthostatic hypotension than patients with SBP more than 140 mmHg (respectively, 13 vs. 23%; P < 0.001). Individuals with orthostatic hypotension exhibited higher brachial and central PP than individuals without orthostatic hypotension (respectively, 69+/-18 vs. 65+/-16 mmHg and 57+/-17 vs. 54+/-15 mmHg; P < 0.01). In these same individuals, a significant increase in augmentation index (31.1+/-14.0 vs. 27.2+/ 13.6%; P < 0.01), but not in cf-PWV or in PPA, was observed. Individuals with orthostatic hypotension were treated more frequently with beta-blockers and less frequently with angiotensin receptor blockers or nitrates than individuals without orthostatic hypotension (P < 0.05 for both). CONCLUSION: Contrary to the general belief, elderly individuals with well controlled BP (SBP < 140 mmHg) show lower orthostatic hypotension, thus constituting a complementary argument for efficaciously treating hypertension in these individuals. PMID- 22080224 TI - Modelling the impact on avoidable cardiovascular disease burden and costs of interventions to lower SBP in the England population. AB - BACKGROUND: The burden of disease from cardiovascular disease (CVD) remains significant in England. Blood pressure remains an important risk factor. Health gain through public health measures and improving treatment compliance are potentially likely to be high. We assess the impact of known cost-effective interventions in terms of the avoidable CVD burden and costs by comparing these strategies to the current situation. METHODS: We modelled avoidable CVD outcomes simulating the English population aged over 16 years with Excel spreadsheets for the current prevention/treatment and following various interventions over a 10 year time frame. The outcome measures were avoidable incident heart disease and stroke events, deaths and disability-adjusted life years (DALYs). Costs are reported from the health service perspective. We analysed relative cost effectiveness, undertook sensitivity analysis and measured relative impacts of different strategies on avoidable burden of disease. RESULTS: The assessed interventions have a potential to reduce the current burden of disease between 70 000 and about 1 million DALYs over the 10-year frame. Although all interventions were cost-effective, some (e.g. Salt reduction in the population and 'Dietary Approaches to Stop Hypertension-sodium', which modelled the impact of salt reduction and dietary approaches) were cost-saving. The cost-effectiveness of treatment strategies was sensitive to drug costs. CONCLUSION: Evidence-based interventions appropriately scaled up for both prevention and treatment of blood pressure lead to important additional potential health gains. There was noticeable variance in cost-effectiveness and impact among the different interventions at a population level. Taking into account impact, priority should be given to prevention to reduce blood pressure at a population level through reduced salt consumption. PMID- 22080225 TI - Microalbuminuria breakthrough under chronic renin-angiotensin-aldosterone system suppression. AB - OBJECTIVES: Microalbuminuria has been shown to be a potent predictor for future development of cardiovascular and renal events that can be prevented by the use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs). Both classes of drugs are now-a-days widely used in the treatment of arterial hypertension since the very early stages of the cardiorenal continuum when only cardiovascular risk factors are detected. We describe here the development of de-novo microalbuminuria in patients chronically treated with either an ACEi or an ARB at adequate doses. METHODS: We reviewed the evolution of 1433 patients (mean age 60.5 +/- 12.4 years, 50.3% men, 6.6% having type 2 diabetes), arriving in our hospital-based Hypertension Unit previously treated for a least 2 years either with an ACEi or an ARB, at adequate doses, alone or in combination with other antihypertensive drugs. RESULTS: A total of 184 (16.1%) patients developed new-onset microalbuminuria, whereas macroalbuminuria was detected in 11 (1.0%) patients at the end of follow-up. Albuminuria appeared at any level of blood pressure (BP) from below 130/80 mmHg, albeit the highest percentage was seen when SBP was above 160 mmHg. De-novo microalbuminuria was more frequent in those patients presenting with established cardiovascular disease and predicts the future development of cardiovascular events but was not accompanied by a significant worsening of renal function. CONCLUSION: These data indicate that a reappraisal of renin-angiotensin-aldosterone system (RAAS) suppression is required when microalbuminuria appears in patients under chronic RAAS suppression. PMID- 22080226 TI - In-vivo administration of CLC-K kidney chloride channels inhibitors increases water diuresis in rats: a new drug target for hypertension? AB - OBJECTIVE: The human kidney-specific chloride channels ClC-Ka (rodent ClC-K1) and ClC-Kb (rodent ClC-K2) are important determinants of renal function, participating to urine concentration and blood pressure regulation mechanisms. Here we tested the hypothesis that these chloride channels could represent new drug targets for inducing diuretic and antihypertensive effects. METHODS: To this purpose, the CLC-K blockers benzofuran derivatives MT-189 and RT-93 (10, 50, 100 mg/kg), were acutely administered by gavage in Wistar rats, and pharmacodynamic and pharmacokinetic parameters determined by functional, bioanalytical, biochemical and molecular biology assays. RESULTS: Plasma concentration values for MT-189 and RT-93 were indicative of good bioavailability. Both MT-189 and RT 93 dose-dependently increased urine volume without affecting electrolyte balance. A comparable reduction of SBP was observed in rats after MT-189, RT-93 or furosemide administration. Benzofuran derivatives treatment did not affect kidney CLC-K mRNA level or inner medulla osmolality, whereas a significant vasopressin independent down-regulation of aquaporin water channel type 2 was observed at protein and transcriptional levels. In rats treated with benzofuran derivatives, the observed polyuria was mainly water diuresis; this finding indirectly supports a cross-talk between chloride and water transport in nephron. Moreover, preliminary in-vitro evaluation of the drugs capability to cross the blood-inner ear barrier suggests that these compounds have a limited ability to induce potential auditory side effects. CONCLUSION: CLC-K blockers may represent a new class of drugs for the treatment of conditions associated with expanded extracellular volume, with a hopeful high therapeutic potential for hypertensive patients carrying ClC-K gain-of-function polymorphisms. PMID- 22080227 TI - The mathematical origins of the kinetic compensation effect: 2. The effect of systematic errors. AB - The kinetic compensation effect states that there is a linear relationship between Arrhenius parameters ln A and E for a family of related processes. It is a widely observed phenomenon in many areas of science, notably heterogeneous catalysis. This paper explores mathematical, rather than physicochemical, explanations for the compensation effect in certain situations. Three different topics are covered theoretically and illustrated by examples. Firstly, the effect of systematic errors in experimental kinetic data is explored, and it is shown that these create apparent compensation effects. Secondly, analysis of kinetic data when the Arrhenius parameters depend on another parameter is examined. In the case of temperature programmed desorption (TPD) experiments when the activation energy depends on surface coverage, it is shown that a common analysis method induces a systematic error, causing an apparent compensation effect. Thirdly, the effect of analysing the temperature dependence of an overall rate of reaction, rather than a rate constant, is investigated. It is shown that this can create an apparent compensation effect, but only under some conditions. This result is illustrated by a case study for a unimolecular reaction on a catalyst surface. Overall, the work highlights the fact that, whenever a kinetic compensation effect is observed experimentally, the possibility of it having a mathematical origin should be carefully considered before any physicochemical conclusions are drawn. PMID- 22080229 TI - Seeding approach to noble metal decorated conducting polymer nanofiber network. AB - Metal displacement reactions between conducting polymers-"synthetic metals"-and noble metals (Pt, Au and Ag) have been demonstrated using a seeding polymerization technique, to produce a synthetic metal nanofiber network decorated with noble metal nanoparticles, in one-step. PMID- 22080228 TI - Chlamydomonas reinhardtii as a viable platform for the production of recombinant proteins: current status and perspectives. AB - Chlamydomonas reinhardtii has many advantages compared with traditional systems for the molecular farming of recombinant proteins. These include low production costs, rapid scalability at pilot level, absence of human pathogens and the ability to fold and assemble complex proteins accurately. Currently, the successful expression of several proteins with pharmaceutical relevance has been reported from the nuclear and the chloroplastic genome of this alga, demonstrating its usefulness for biotechnological applications. However, several factors affect the level of recombinant protein expression in Chlamydomonas such as enhancer elements, codon dependency, sensitivity to proteases and transformation-associated genotypic modification. The present review outlines a number of strategies to increase protein yields and summarizes recent achievements in algal protein production including biopharmaceuticals such as vaccines, antibodies, hormones and enzymes with implications on health-related approaches. The current status of bioreactor developments for algal culture and the challenges of scale-up and optimization processes are also discussed. PMID- 22080230 TI - Pathophysiology of postprandial hyperglycaemia in women with type 1 diabetes during pregnancy. AB - AIMS/HYPOTHESIS: Although maternal hyperglycaemia is associated with increased risk of adverse pregnancy outcome, the mechanisms of postprandial hyperglycaemia during pregnancy are poorly understood. We aimed to describe glucose turnover in pregnant women with type 1 diabetes, according to stage of gestation (early vs late gestation). METHODS: The rates of systemic glucose appearance (R(a)) and glucose disposal (R(d)) were measured in ten pregnant women with type 1 diabetes during early (12-16 weeks) and late (28-32 weeks) gestation. Women ate standardised meals--a starch-rich 80 g carbohydrate dinner and a sugar-rich 60 g carbohydrate breakfast--and fasted between meals and overnight. Stable-label isotope tracers ([6,6-(2)H(2)]glucose and [U-(13)C]glucose) were used to determine R(a), R(d) and glucose bioavailability. Closed-loop insulin delivery maintained stable glycaemic conditions. RESULTS: There were no changes in fasting R(a) (10 +/- 2 vs 11 +/- 2 MUmol kg(-1) min(-1); p = 0.32) or fasting R(d) (11 +/ 2 vs 11 +/- 1 MUmol kg(-1) min(-1); p = 0.77) in early vs late gestation. There was increased hepatic insulin resistance (381 +/- 237 vs 540 +/- 242 MUmol kg(-1) min(-1) * pmol/l; p = 0.04) and decreased peripheral insulin sensitivity (0.09 +/ 0.04 vs 0.05 +/- 0.02 MUmol kg(-1) min(-1) per pmol/l dinner, 0.11 +/- 0.05 vs 0.07 +/- 0.03 MUmol kg(-1) min(-1) per pmol/l breakfast; p = 0.002) in late gestation. It also took longer for insulin levels to reach maximal concentrations (49 [37-55] vs 71 [52-108] min; p = 0.004) with significantly delayed glucose disposal (108 [87-125] vs 135 [110-158] min; p = 0.005) in late gestation. CONCLUSIONS/INTERPRETATION: Postprandial glucose control is impaired by significantly slower glucose disposal in late gestation. Early prandial insulin dosing may help to accelerate glucose disposal and potentially ameliorate postprandial hyperglycaemia in late pregnancy. TRIAL REGISTRATION: ISRCTN 62568875 FUNDING: Diabetes UK Project Grant BDA 07/003551. H.R. Murphy is funded by a National Institute for Health Research (NIHR) research fellowship (PDF/08/01/036). Supported also by the Juvenile Diabetes Research Foundation (JDRF), Abbott Diabetes Care (Freestyle Navigator CGM and sensors free of charge), Medical Research Council Centre for Obesity and Related Metabolic Diseases and NIHR Cambridge Biomedical Research Centre. PMID- 22080231 TI - Diabetes: impaired damage control. AB - A coordinated response by the innate immune system, (micro)circulation and nervous system is needed to limit tissue destruction and to initiate reparative processes after tissue damage. Alterations in danger signals in diabetes can be an important cause of the excessive tissue loss and defective tissue repair after injury and can contribute to the higher rates of cardiac failure after myocardial infarction, more severe tissue loss in the case of peripheral ischaemia and impaired wound healing. Here we discuss the mechanisms underlying this impaired damage control in diabetes, with an emphasis on the proinflammatory cytokine high mobility group box 1 and the potential role of dipeptidyl peptidase IV inhibition in improving repair responses. PMID- 22080232 TI - Detecting scale violations in absence of mismatch requires music-syntactic analysis: a further look at the early right anterior negativity (ERAN). AB - The purpose of this study was to determine whether infrequent scale violations in a sequence of in-key notes are detected when the deviants are matched for frequency of occurrence and preceding intervals with the control notes. We further investigated whether the detectability of scale violations is modulated by the presence of melodic context and by the level of musical training. Event related potentials were recorded from 14 musicians and 13 non-musicians. In non musicians, the out-of-key notes elicited an early right anterior negativity (ERAN), which appeared prominently over right frontal sites only when presented within structured sequences; no effects were found when the out-of-key notes were presented within scrambled sequences. In musicians, the out-of-key notes elicited a similar bilateral ERAN in structured and scrambled sequences. Our findings suggest that scale information is processed at the level of music-syntactic analysis, and that the detection of deviants does not require activation of auditory sensory memory by mismatch effects. Scales are perceived as a broader context, not just as online interval relations. Additional melodic context information appears necessary to support the representation of scale deviants in non-musicians, but not in musically-trained individuals, likely as a consequence of stronger pre-existing representations. PMID- 22080233 TI - Increasing visible-light absorption for photocatalysis with black BiOCl. AB - Black BiOCl with oxygen vacancies was prepared by UV light irradiation with Ar blowing. The as-prepared black BiOCl sample showed 20 times higher visible light photocatalytic activity than white BiOCl for RhB degradation. The trapping experiment showed that the superoxide radical (O(2)(*-)) and holes (h(+)) were the main active species in aqueous solution under visible light irradiation. PMID- 22080234 TI - Catechin protects against oxidative stress and inflammatory-mediated cardiotoxicity in adriamycin-treated rats. AB - Catechin has anti-inflammatory and antioxidative effects. Cardiotoxicity, which results from intense cardiac oxidative stress and inflammation, is the main limiting factor of the adriamycin use in the treatment of malignant tumors. Thus, the present study aimed to assess the antioxidant and anti-inflammatory effects of catechin on adriamycin-induced cardiotoxicity in rats. Forty-five rats were allocated to three groups: control group, adriamycin group and adriamycin + catechin group. We performed the following measurements: lipid peroxidation (MDA), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities as well as, the expression of inflammatory cytokines genes namely nuclear factor kappa-B, tumor necrosis factor and inducible nitric oxide synthase. Catechin administration significantly decreased MDA level and significantly increased CAT, GSH-Px and SOD activities. Also, catechin significantly decreased the expression levels of inflammatory cytokines. Catechin provided cardioprotection on adriamycin-induced cardiotoxicity through their antioxidant and anti-inflammatory properties. PMID- 22080235 TI - Antiproliferative in vitro effects of BI 2536-mediated PLK1 inhibition on cervical adenocarcinoma cells. AB - Cervical adenocarcinoma is one of the most common gynecological malignancies. Despite the improvements in multimodality treatment, advanced disease is still associated with a significantly poor prognosis making the search for more effective therapeutic agents imperative. BI 2536, an unambiguous inhibitor of Polo-like kinase 1 (PLK1), has shown anticancer activity in a variety of tumor cell types. Herein, we present more evidence of the antiproliferative effects of this drug on HeLa cells. Nanomolar concentrations (10-100 nmol/l) of the drug significantly decreased cell proliferation and clonogenic capacity. Our results also demonstrate that inhibition of PLK1 promoted G2/M arrest and resulted in a dramatic increase in the mitotic index after 24 h of treatment. Apoptosis onset was evinced by the accumulation of a sub-G1 population as well as by a significant increase in caspase-3 activity at longer periods of exposure. Taken together, our results reinforce the prospect of directing against PLK1 as a potential therapeutic target to be evaluated in different preclinical models for cervical carcinoma. PMID- 22080236 TI - Tissue effects of intracorporeal lithotripsy techniques during percutaneous nephrolithotomy: comparison of pneumatic and ultrasonic lithotripters on rat bladder. AB - The objectives of this study were to determine the tissue effects of ultrasonic and pneumatic lithotripsy on the rat urothelium. The rats were divided into three groups. Groups I and II consisted of ten rats each that underwent intracorporeal lithotripsy (pneumatic and ultrasonic lithotripsy, respectively). Group III contained ten control rats and no lithotripsy method was used, they served as references for absence of injury. The light microscopy findings were evaluated as follows: squamous metaplasia, papillary projection, inflammation, increased stratification, and stone formation. In five (71.4%) animals of group II, bladders were edematous and hemorrhagic, macroscopically. Histologically, the bladder wall was normal in four rats of group I and in one of group II. There was a significant increase in inflammation (31.5%), squamous metaplasia (85.7%), papillary projection (71.4%), increased stratification (71.4%), and microscopic or macroscopic stone formation (85.7%) in the bladder wall of group II rats in comparison with group I and control group. In the rat model, we noted that ultrasonic devices have a potential risk for tissue injury. In turn, this was associated with a markedly increased deposition of CaOx stones in the kidney. When confronted with harder stones, pneumatic lithotripsy can be more effective while also minimizing tissue injury. PMID- 22080237 TI - Left unilateral electroconvulsive therapy (ECT) after oligodendroglioma resection. AB - A 44-year-old man with a previously resected right parietal oligodendroglioma received left unilateral electroconvulsive therapy (ECT). We present images of his brain magnetic resonance imaging, ECT electrode placement, and the electroencephalogram tracing from his ECT. PMID- 22080238 TI - The effect of repeated etomidate anesthesia on adrenocortical function during a course of electroconvulsive therapy. AB - BACKGROUND: Etomidate may affect adrenocortical function. We conducted an investigation of the comparative effects of etomidate and propofol during electroconvulsive therapy (ECT) on adrenocortical function and hemodynamics. METHODS: Patients in group T received etomidate and those in group B received propofol during intravenous anesthesia in ECT. Patients underwent ECT once every 2 days for 6 times. The serum levels of cortisol (Cor) and adrenocorticotropic hormone were determined 5 minutes before first anesthesia (baseline level, D0), and 24 hours (D1) as well as 48 hours after the last ECT (D2). At the same time, the hemodynamics was measured 2 minutes before anesthetic induction (T0), 30 seconds (T1) and 20 minutes after ECT (T2). Electrographic seizure duration (t), average seizure energy index, and postictal suppression index were recorded. RESULTS: Compared with the baseline level, serum Cor levels in group T were markedly decreased, but in normal ranges, at 24 hours after second and sixth treatments. No significant difference in serum Cor level was observed between the baseline and 48 hours posttreatment. In group B, there was no significant difference in serum Cor level between the baseline and 24 hours as well as 48 hours after each treatment. Furthermore, no significant difference in adrenocorticotropic hormone level was observed between the baseline and 24 hours as well as 48 hours posttreatment. However, the hemodynamics markedly changed during ECT and reached the preanesthetic level at 20 minutes posttreatment. The ECT-induced seizure duration in group T was longer than that in group B. However, seizure energy index and postictal suppression index was not significantly different between groups T and B. CONCLUSIONS: Etomidate and propofol would not affect the adrenocortical function during ECT, and hemodynamics reached normal level in a short time after ECT. Etomidate and propofol were both safe intravenous anesthetics during ECT, although etomidate was associated with comparatively longer seizure duration. PMID- 22080239 TI - A conceptual introduction to cognitive remediation for memory deficits associated with right unilateral electroconvulsive therapy. AB - OBJECTIVE: Although electroconvulsive therapy (ECT) is a highly effective treatment for people with severe depression, many patients report that treatment induced memory problems are the most disturbing and serious adverse effects, affecting quality of life after treatment and willingness to consent to further ECT sessions. To date, no intervention to mitigate these cognitive deficits has been developed. We introduce the methodology of a novel cognitive training program called Memory Training for ECT (Mem-ECT) that is based on cognitive training in seizure disorders. Mem-ECT is designed to help memories that are usually compromised after ECT to remain relatively preserved. METHODS: We evaluated the feasibility of implementing Mem-ECT in 8 adult patients with a diagnosis of major depressive disorder who underwent right unilateral ECT. This open pilot trial assessed recruitment procedures and treatment feasibility such as patient's burden and compliance, exercise length, and how best to integrate treatment sessions around the patient's schedule before undergoing ECT. RESULTS: We found Mem-ECT to be fairly well tolerated by depressed inpatients and easily implemented within ECT treatment services. CONCLUSION: We discuss issues for future development, including an ongoing treatment-masked controlled study we are conducting to test the efficacy of Mem-ECT. Developing a safe and effective behavioral strategy to minimize ECT's adverse effects on memory may make ECT a more easily tolerated treatment. PMID- 22080240 TI - Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for the treatment of major depressive disorder, a randomized controlled clinical trial. AB - INTRODUCTION: Studies comparing the antidepressant effects of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) have reported mixed results. This study compared the efficacy of rTMS and ECT in adult patients with refractory major depressive disorder (MDD). METHODS: This randomized, ECT-controlled, parallel-group clinical trial analyzed the antidepressant effects of ECT and rTMS in 73 patients with MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. The Beck Depression Inventory and Hamilton Depression Rating Scale were used to measure depression. RESULTS: Both ECT and rTMS significantly improved depression and suicidal behavior scores. However, ECT reduced depression and suicidal behavior scores more than rTMS. There were no significant adverse effects in the rTMS group. DISCUSSION: Both ECT and rTMS improved MDD in the short term, but the antidepressant efficacy of ECT was greater than rTMS. Moreover, ECT led to greater reductions in suicidal behavior than rTMS. Until strong evidence for the safety and efficacy of rTMS is available, further studies are needed to compare ECT and rTMS in terms of the long-term relapse rate and quality of life. PMID- 22080241 TI - The role of psychosocial factors in the course of pain--a 1-year follow-up study among women living in Sweden. AB - The understanding of the associations between psychosocial factors and persistent pain and their impact on the course of pain among women is crucial to identify risk populations and prevent long-term pain from developing. The aim of the study was to investigate the course of pain among women and the psychosocial factors associated with it. The study was a 1-year follow-up (FU) among 2,300 women in the general population of Sweden. Sociodemographic and psychosocial factors were analyzed in relation to the course of pain, assessed as the presence of pain during the last 3 months at baseline (BL) and at FU. Thirty-three percent of the women with no pain at BL and 77% of those with pain at BL reported pain at FU. Compared to the pain-free women, those who developed pain at FU reported lower social support and physical quality of life (QoL) and worse mental health. Women with sustained pain were older and reported worse mental health, lack of social support, and lower levels of QoL compared to those who recovered from pain. In the multiple logistic regression analyses, only post-traumatic stress symptoms were associated with the development of pain at FU. Number of pain locations and pain duration at BL and physical QoL were associated with sustained pain. Moreover, social support was identified as a protective factor against sustained pain. Pain is persistent or recurrent in a general female population. The results indicate that psychosocial factors do not work as primary predictors in the course of pain and might be better understood through indirect processes by limiting the individual's resources for handling pain in a functional manner. PMID- 22080242 TI - Contact printing a biomimetic catecholic monolayer on a variety of surfaces and derivation reaction. AB - Biomimic catecholic "ink" is employed in surface patterning by using microcontact printing (MUCP) on a variety of surfaces. The surface chemical patterning can be proofed by implementing a derivation reaction, such as specific biological recognition and surface-initiated polymerization for growth of polymer brushes. PMID- 22080243 TI - Graphene: nanoscale processing and recent applications. AB - One of the most interesting features of graphene is the rich physics set up by the various nanostructures it may adopt. The planar structure of graphene makes this material ideal for patterning at the nanoscale. The breathtakingly fast evolution of research on graphene growth and preparation methods has made possible the preparation of samples with arbitrary sizes. Available sample production techniques, combined with the right patterning tools, can be used to tailor the graphene sheet into functional nanostructures, even whole electronic circuits. This paper is a review of the existing graphene patterning techniques and potential applications of related lithographic methods. PMID- 22080245 TI - Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer. AB - Prior studies have suggested a higher prevalence of high grade, ER-negative, HER2 positive, and basal-like carcinomas in young women with breast cancer. However, the precise distribution of poor prognostic features in this population remains unclear. We examined the pathologic features and distribution of molecular phenotype in relation to patient age in a large group of young women (<=40 years) with invasive breast cancer. Medical records were reviewed for clinical characteristics, tumor stage, and receptor status. Pathologic features, including those features associated with basal-like carcinomas, were examined by central review. Using tumor grade and biomarker expression, cancers were categorized as luminal A (ER+ and/or PR+ and HER2-, histologic grade 1 or 2); luminal B (ER+ and/or PR+ and HER2+, or ER and/or PR+, HER2- and grade 3); HER2 (ER and PR- and HER2+); and triple negative (ER-, PR-, and HER2-). Among 399 women of <=40 years, 33% had luminal A tumors, 35% luminal B, 11% HER2 (ER-negative), and 21% triple negative. Compared to published results for all breast cancers, a greater proportion of young women had luminal B tumors, and a lesser proportion had luminal A. There were no significant differences in molecular phenotype, tumor stage or grade among the different age groups of young women. However, this population of young women presented with a different distribution of molecular phenotypes compared to the general population of women with breast cancer. These findings may have implications with regard to the etiology and prognosis of breast cancer in young women. PMID- 22080244 TI - Cadherin-catenin complex dissociation in lobular neoplasia of the breast. AB - E-cadherin (E-CD) inactivation with loss of E-CD-mediated cell adhesion is the hallmark of lesions of the lobular phenotype. E-CD is typically absent by immunohistochemistry in both lobular carcinoma in situ (LCIS) and invasive lobular lesions, suggesting it occurs early in the neoplastic process. In laboratory models, downstream post-transcriptional modifiers such as TWIST and SNAIL contribute to the dissociation of the intracellular component of the cadherin-catenin complex (CCC), resulting in tumor progression and invasion. We hypothesized that complete CCC dissociation may play a role in lobular neoplasia progression. Here we explore the relationship between loss of E-CD and dissociation of the CCC in pure LCIS and LCIS associated with invasive cancer. Fresh-frozen tissues were obtained from 36 patients undergoing mastectomy for pure LCIS (n = 11), LCIS with ILC (n = 18) or LCIS with IDC (n = 7). Individual lesions were subject to laser-capture microdissection and gene-expression analysis (Affymetrix HG-U133A 2.0). Immunohistochemistry for ER,PR,HER2, E-CD,N CD,alpha-,beta-, and phosphobeta-catenin, TWIST, and SNAIL were evaluated in normal, in situ, and invasive components from matched formalin-fixed paraffin embedded samples (n = 36). CCC-dissociation was defined as negative membranous E CD, alpha- and beta-catenin expression. E-CD was negative in all LCIS and ILC lesions, and positive in all normal and IDC lesions. Membranous alpha and beta catenin expressions decreased with the transition from LCIS to ILC (pure LCIS 82%; LCIS w/ILC 28%; ILC 0%), while TWIST expression increased (pure LCIS low; LCIS w/ILC moderate; ILC high). Gene expression paralleled IHC-staining patterns with a stepwise downregulation of E-CD, alpha and beta-catenins from normal to LCIS to invasive lesions, and increasing expression of TWIST from normal to LCIS to ILC. Loss of E-CD expression is an early event in lobular neoplasia. Decreasing membranous catenin expression in tandem with increasing levels of TWIST across the spectrum of lobular lesions suggests that CCC dissociation is a progressive process. PMID- 22080246 TI - Endocrine therapy in obese patients with primary breast cancer: another piece of evidence in an unfinished puzzle. AB - Obesity, defined as a body mass index (BMI) >=30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877 (18.9%) a BMI >=30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15-1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03-1.65)). In hormone-receptor-negative (HR-) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80-1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24-2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS (P = 0.202; HR = 1.44 (95% CI: 0.82 2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63-2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29-1.45)). In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen. Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed. PMID- 22080247 TI - Nanorainforest solar cells based on multi-junction hierarchical p-Si/n-CdS/n-ZnO nanoheterostructures. AB - Solar cells based on one-dimensional nanostructures have recently emerged as one of the most promising candidates to achieve high-efficiency solar energy conversion due to their reduced optical reflection, enhanced light absorption, and enhanced carrier collection. In nature, the rainforest, consisting of several stereo layers of vegetation, is the highest solar-energy-using ecosystem. Herein, we gave an imitation of the rainforest configuration in nanostructure-based solar cell design. Novel multi-layer nanorainforest solar cells based on p-Si nanopillar array/n-CdS nanoparticles/n-ZnO nanowire array heterostructures were achieved via a highly accessible, reproducible and controllable fabrication process. By choosing materials with appropriate bandgaps, an efficient light absorption and enhanced light harvesting were achieved due to the wide range of the solar spectrum covered. Si nanopillar arrays were introduced as direct conduction pathways for photon-generated charges' efficient collection and transport. The unique strategy using PMMA as a void-filling material to obtain a continuous, uniform and low resistance front electrode has significantly improved the overall light conversion efficiency by two orders of magnitude. These results demonstrate that nanorainforest solar cells, along with wafer-scale, low-cost and easily controlled processing, open up substantial opportunities for nanostructure photovoltaic devices. PMID- 22080248 TI - Photogenerated avenues in macromolecules containing Re(I), Ru(II), Os(II), and Ir(III) metal complexes of pyridine-based ligands. AB - Pyridine-based ligands, such as 2,2'-bipyridine and 1,10-phenanthroline, have gained much interest in the fields of supramolecular chemistry as well as materials science. The appealing optoelectronic properties of their complexes with heavy d(6) transition metal ions, such as Ru(ii), Os(II), Re(I) and Ir(III), primarily based on the metal-to-ligand charge-transfer (MLCT) nature featuring access to charge-separated states, have provided the starting point for many studies in the field of dye-sensitized solar cells (DSSCs), organic light emitting diodes (OLEDs), artificial photosynthesis and photogenerated electron as well as energy transfer processes. This critical review provides a comprehensive survey over central advances in the field of soluble metal-containing macromolecules in the last few decades. The synthesis and properties of functionalized 2,2'-bipyridyine- and 1,10-phenanthroline-based d(6) metal complexes, in particular, their introduction into different prevailing polymeric structures are highlighted. In the most part of the review metal complexes which have been attached as pendant groups on the polymer side chain are covered. Selected applications of the herein discussed metal-containing macromolecules are addressed, particularly, with respect to photogenerated electron/energy transfer processes. In order to enable a deeper understanding of the properties of the ligands and metal complexes, the fundamentals of selected photophysical processes will be discussed (223 references). PMID- 22080249 TI - The phenomenology of autistic regression: subtypes and associated factors. AB - This study aimed to investigate the association of autistic regression (AR) and subtypes of AR with medical, developmental and psychiatric factors. Fifty-seven children with autistic spectrum disorders (ASD) were included in the study. Two types of AR are defined as regression after a normal social/language development (type 1) and regression as the worsening of previously reported autistic features (type 2). The frequency of history of AR was 56.1%. Male gender and sleep problems were found to be associated with a positive history of AR. The frequency of gastrointestinal complaints/diseases was higher in children with regression type 2 when compared to the children with regression type 1. Future studies with larger sample size and prospective design will contribute to clarifying the phenomenology and the associated factors of AR. PMID- 22080250 TI - Effects of microperfusion in hepatic diffusion weighted imaging. AB - OBJECTIVE: Clinical hepatic diffusion weighted imaging (DWI) generally relies on mono-exponential diffusion. The aim was to demonstrate that mono-exponential diffusion in the liver is contaminated by microperfusion and that the bi exponential model is required. METHODS: Nineteen fasting healthy volunteers were examined with DWI (seven b-values) using fat suppression and respiratory triggering (1.5 T). Five different regions in the liver were analysed regarding the mono-exponentially fitted apparent diffusion coefficient (ADC), and the bi exponential model: molecular diffusion (D (slow)), microperfusion (D (fast)) and the respective fractions (f (slow/fast)). Data were compared using ANOVA and Kruskal-Wallis tests. Simulations were performed by repeating our data analyses, using just the DWI series acquired with b-values approximating those of previous studies. RESULTS: Median mono-exponentially fitted ADCs varied significantly (P < 0.001) between 1.107 and 1.423 * 10(-3) mm(2)/s for the five regions. Bi exponential fitted D(slow) varied between 0.923 and 1.062 * 10(-3) mm(2)/s without significant differences (P = 0.140). D (fast) varied significantly, between 17.8 and 46.8 * 10(-3) mm(2)/s (P < 0.001). F-tests showed that the diffusion data fitted the bi-exponential model significantly better than the mono exponential model (F > 21.4, P < 0.010). These results were confirmed by the simulations. CONCLUSION: ADCs of normal liver tissue are significantly dependent on the measurement location because of substantial microperfusion contamination; therefore the bi-exponential model should be used. KEY POINTS: Diffusion weighted MR imaging helps clinicians to differentiate tumours by diffusion properties. Fast moving water molecules experience microperfusion, slow molecules diffusion. Hepatic diffusion should be measured by bi-exponential models to avoid microperfusion contamination. Mono-exponential models are contaminated with microperfusion, resulting in apparent regional diffusion differences. Bi exponential models are necessary to measure diffusion and microperfusion in the liver. PMID- 22080251 TI - Are contrast media required for (68)Ga-DOTATOC PET/CT in patients with neuroendocrine tumours of the abdomen? AB - OBJECTIVES: To determine the value of intravenous contrast medium in (68)Ga-DOTA Phe(1)-Tyr(3)-octreotide - (68)Ga-DOTATOC - PET/CT for the detection of abdominal neuroendocrine tumours (NET). METHODS: In fifty-five patients with known or suspected NETs of the abdomen PET/CT was performed on a 64-row multi-detector hybrid system. For PET, 150 MBq of (68)Ga-DOTATOC were injected intravenously. Full-dose unenhanced, and arterial- and venous-phase contrast-enhanced CT images were obtained. Unenhanced and contrast-enhanced PET/CT images were evaluated separately for the presence of NETs on a per-region basis, by two separate teams with different experience levels. RESULTS: On unenhanced PET/CT, sensitivity and specificity ranged from 89.3% (junior team) to 92% (senior team), and 99.1% (junior team) to 99.2% (senior team), respectively. On contrast-enhanced PET/CT, sensitivity and specificity ranged from 92.3% (junior team) to 98.5% (senior team), and 99.4% (junior team) to 99.5% (senior team), respectively. These increases in sensitivity and specificity, due to the use of contrast-enhanced images, were statistically significant (P < 0.05). CONCLUSIONS: Intravenous contrast medium only moderately, aleit significantly, improves the sensitivity of (68)Ga-DOTATOC PET/CT for the detection of abdominal NETs, and hardly affects specificity. Thus, while contrast enhancement is justified to achieve maximum sensitivity, unenhanced images may be sufficient for routine PET/CT in NET patients. KEY POINTS: Contrast media moderately improve the sensitivity of (68)Ga DOTATOC PET/CT for neuroendocrine tumours. Contrast media hardly affect the specificity of (68)Ga-DOTATOC PET/CT for neuroendocrine tumours. Unenhanced PET/CT is sufficient for routine imaging of patients with neuroendocrine tumours. PMID- 22080253 TI - Effects of pollen supply and quality on seed formation and maturation in Pinus densiflora. AB - To understand the detailed mechanisms underlying variations in seed productivity per cone, it is important to examine simultaneously the effects of two pollination mode components (pollen supply and quality) on two seed production processes (seed formation and maturation). We conducted artificial pollination experiments with four pollination treatments (selfing, polycross, no-pollination and open-pollination treatments) in each of two vertical crown layers (upper and lower) for 19 Pinus densiflora ramets. We measured formed seeds as a proportion of ovules (P(Form)), and filled seeds as a proportion of formed seeds (P(Fill)) per cone in each treatment and layer, and inferred the relative influences of pollination mode and resource availability on seed productivity. In the no pollination treatment, no seeds were formed in any cones of all five ramets. The Generalized Linear Model showed that there were no significant differences in P(Form) both between selfing and polycross treatments and upper and lower layers. The mean P(Fill) values in the selfing treatment were significantly lower than those in the polycross treatment in both layers. The mean P(Fill)s of the two layers did not differ significantly in the selfing treatment, but did in the open pollination and polycross treatments. The results show that pollen supply affects mainly seed formation, whereas pollen quality affects mainly seed maturation. Resource availability also affects mainly seed maturation, if pollen quality is higher than a certain threshold. PMID- 22080252 TI - Involvement of the putative Ca2+-permeable mechanosensitive channels, NtMCA1 and NtMCA2, in Ca2+ uptake, Ca2+-dependent cell proliferation and mechanical stress induced gene expression in tobacco (Nicotiana tabacum) BY-2 cells. AB - To gain insight into the cellular functions of the mid1-complementing activity (MCA) family proteins, encoding putative Ca2+-permeable mechanosensitive channels, we isolated two MCA homologs of tobacco (Nicotiana tabacum) BY-2 cells, named NtMCA1 and NtMCA2. NtMCA1 and NtMCA2 partially complemented the lethality and Ca2+ uptake defects of yeast mutants lacking mechanosensitive Ca2+ channel components. Furthermore, in yeast cells overexpressing NtMCA1 and NtMCA2, the hypo-osmotic shock-induced Ca2+ influx was enhanced. Overexpression of NtMCA1 or NtMCA2 in BY-2 cells enhanced Ca2+ uptake, and significantly alleviated growth inhibition under Ca2+ limitation. NtMCA1-overexpressing BY-2 cells showed higher sensitivity to hypo-osmotic shock than control cells, and induced the expression of the touch-inducible gene, NtERF4. We found that both NtMCA1-GFP and NtMCA2-GFP were localized at the plasma membrane and its interface with the cell wall, Hechtian strands, and at the cell plate and perinuclear vesicles of dividing cells. NtMCA2 transcript levels fluctuated during the cell cycle and were highest at the G1 phase. These results suggest that NtMCA1 and NtMCA2 play roles in Ca2+ dependent cell proliferation and mechanical stress-induced gene expression in BY 2 cells, by regulating the Ca2+ influx through the plasma membrane. PMID- 22080254 TI - The joint association of physical activity and glycaemic control in predicting cardiovascular death and all-cause mortality in the US population. AB - AIMS/HYPOTHESIS: The aim of this study was to examine the joint association of physical activity and glycaemic control as measured by HbA(1c) on all-cause and cardiovascular disease (CVD) mortality risk. METHODS: The sample included 10,352 adults from the Third National Health and Nutrition Examination Survey (NHANES III) Linked Mortality Public-use File (follow-up 13.4 +/- 3.9 years; 2,463 deaths). Physical activity was assessed by questionnaire and classified into inactive and active categories based on self-reported frequency of leisure-time activity. HbA(1c) was categorised to reflect the American Diabetes Association diagnostic and treatment guidelines. RESULTS: Being physically active was associated with a decreased risk of all-cause (HR 0.74 [95% CI 0.67, 0.81]) and CVD (HR 0.71 [95% CI 0.62, 0.82]) mortality, whereas higher levels of HbA(1c) were associated with an increased mortality risk. HbA(1c) >= 7% (53 mmol/mol) was associated with the highest risk for all-cause (HR 1.54 [95% CI 1.30, 1.82]) and CVD (HR 1.93 [95% CI 1.52, 2.45]) mortality. Across all categories of HbA(1c), active individuals were not at increased risk for all-cause mortality compared with inactive individuals with normal glycaemic control. Similar findings were observed for CVD mortality, except that active individuals with HbA(1c) >= 7% (53 mmol/mol) were still at increased risk for CVD mortality. However, their risk for CVD death was substantially lower than the risk for their inactive counterparts (HR 1.38 [95% CI 1.03, 1.84] vs HR 1.98 [95% CI 1.34, 2.92]). CONCLUSIONS/INTERPRETATION: Physical activity is associated with lower all-cause and CVD mortality risk for individuals across all levels of glycaemic control. Therefore, engaging in a physically active lifestyle and achieving normal levels of glycaemic control may both be important for the prevention of early mortality. PMID- 22080255 TI - Self-assembling peptide scaffolds for regenerative medicine. AB - Biomaterials made from self-assembling, short peptides and peptide derivatives have great potential to generate powerful new therapies in regenerative medicine. The high signaling capacity and therapeutic efficacy of peptidic scaffolds has been established in several animal models, and the development of more complex, hierarchical structures based on peptide materials is underway. This highlight discusses several classes of self-assembling peptide-based materials, including peptide amphiphiles, Fmoc-peptides, self-complementary ionic peptides, hairpin peptides, and others. The self-assembly designs, bioactive signalling strategies, and cell signalling capabilities of these bioactive materials are reported. The future challenges of the field are also discussed, including short-term goals such as integration with biopolymers and traditional implants, and long term goals, such as immune system programming, subcellular targeting, and the development of highly integrated scaffold systems. PMID- 22080256 TI - Fungal community composition in neotropical rain forests: the influence of tree diversity and precipitation. AB - Plant diversity is considered one factor structuring soil fungal communities because the diversity of compounds in leaf litter might determine the extent of resource heterogeneity for decomposer communities. Lowland tropical rain forests have the highest plant diversity per area of any biome. Since fungi are responsible for much of the decomposition occurring in forest soils, understanding the factors that structure fungi in tropical forests may provide valuable insight for predicting changes in global carbon and nitrogen fluxes. To test the role of plant diversity in shaping fungal community structure and function, soil (0-20 cm) and leaf litter (O horizons) were collected from six established 1-ha forest census plots across a natural plant diversity gradient on the Isthmus of Panama. We used 454 pyrosequencing and phospholipid fatty acid analysis to evaluate correlations between microbial community composition, precipitation, soil nutrients, and plant richness. In soil, the number of fungal taxa increased significantly with increasing mean annual precipitation, but not with plant richness. There were no correlations between fungal communities in leaf litter and plant diversity or precipitation, and fungal communities were found to be compositionally distinct between soil and leaf litter. To directly test for effects of plant species richness on fungal diversity and function, we experimentally re-created litter diversity gradients in litter bags with 1, 25, and 50 species of litter. After 6 months, we found a significant effect of litter diversity on decomposition rate between one and 25 species of leaf litter. However, fungal richness did not track plant species richness. Although studies in a broader range of sites is required, these results suggest that precipitation may be a more important factor than plant diversity or soil nutrient status in structuring tropical forest soil fungal communities. PMID- 22080257 TI - Flowers as islands: spatial distribution of nectar-inhabiting microfungi among plants of Mimulus aurantiacus, a hummingbird-pollinated shrub. AB - Microfungi that inhabit floral nectar offer unique opportunities for the study of microbial distribution and the role that dispersal limitation may play in generating distribution patterns. Flowers are well-replicated habitat islands, among which the microbes disperse via pollinators. This metapopulation system allows for investigation of microbial distribution at multiple spatial scales. We examined the distribution of the yeast, Metschnikowia reukaufii, and other fungal species found in the floral nectar of the sticky monkey flower, Mimulus aurantiacus, a hummingbird-pollinated shrub, at a California site. We found that the frequency of nectar-inhabiting microfungi on a given host plant was not significantly correlated with light availability, nectar volume, or the percent cover of M. aurantiacus around the plant, but was significantly correlated with the location of the host plant and loosely correlated with the density of flowers on the plant. These results suggest that dispersal limitation caused by spatially nonrandom foraging by pollinators may be a primary factor driving the observed distribution pattern. PMID- 22080264 TI - Sexual assault and abuse of children. AB - Testing for sexually transmitted infections (STIs) in children presents a number of problems for the practitioner that are not usually faced when testing adults for the same infections. The identification of an STI in a child can have, in addition to medical implications, serious legal implications. The presence of an STI is often used to support the presence or allegations, or, in some cases, may prompt an investigation of possible abuse. The purpose of this paper is to review the recent data on the epidemiology of child sexual abuse including the epidemiology of major STIs (Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis, herpes simplex virus, Trichomonas vaginalis, and human papillomavirus) and summarize the current recommendations for diagnostic testing in this population. PMID- 22080265 TI - Management of adult syphilis. AB - There are several important unanswered key questions in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these important questions. A single dose of 2.4 million units of benzathine penicillin G remains the drug of choice for managing early syphilis. Enhanced antibiotic therapy has not been shown to improve treatment outcomes, regardless of human immunodeficiency virus (HIV) status. Although additional data on the efficacy of azithromycin in treating early syphilis have emerged, reported increases in the prevalence of a mutation associated with azithromycin resistance precludes a recommendation for its routine use. Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms. In those persons with early syphilis who do not achieve a >= 4-fold serologic decline in their rapid plasma reagin (RPR) titers 6-12 months after adequate therapy and those with late latent infection who do not achieve a similar decline within 12-24 months, CSF examination should be considered. Among HIV-infected persons, CSF examination among all those with asymptomatic late latent syphilis is not recommended owing to lack of evidence that demonstrates clinical benefit. HIV-infected persons with syphilis of any stages whose RPR titers are >= 1:32 and/or whose CD4 cell counts are <350 cells/mm(3) may be at increased risk for asymptomatic neurosyphilis. If CSF pleocytosis is evident at initial CSF examination, these examinations should be repeated every 6 months until the cell count is normal. Several important questions regarding the management of syphilis remain unanswered and should be a priority for future research. PMID- 22080267 TI - Updates on human papillomavirus and genital warts and counseling messages from the 2010 Sexually Transmitted Diseases Treatment Guidelines. AB - BACKGROUND: In April 2009, experts on sexually transmitted diseases (STDs) were convened to review updates on STD prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. At this meeting, there was a discussion of important updates on human papillomavirus (HPV), genital warts, and cervical cancer screening. METHODS: Key questions were identified with assistance from an expert panel, and systematic reviews of the literature were conducted searching the English-language literature of the PubMed computerized database (US National Library of Medicine). The available evidence was reviewed, and new information was incorporated in the 2010 CDC STD Treatment Guidelines. RESULTS: Two HPV vaccines are now available, the quadrivalent HPV vaccine and the bivalent HPV vaccine; either vaccine is recommended routinely for girls aged 11 or 12 years. The quadrivalent HPV vaccine may be given to boys and men aged 9-26 years. A new patient-applied treatment option for genital warts, sinecatechins 15% ointment, is available and recommended for treatment of external genital warts. This product is a mixture of active ingredients (catechins) from green tea. Finally, updated counseling guidelines and messages about HPV, genital warts, and cervical cancer are included. CONCLUSIONS: This manuscript highlights updates to the 2010 CDC STD Treatment Guidelines for HPV and genital warts. Important additions to the 2010 STD Treatment Guidelines include information on prophylactic HPV vaccine recommendations, new patient-applied treatment options for genital warts, and counseling messages for patients on HPV, genital warts, cervical cancer screening, and HPV tests. PMID- 22080266 TI - Mycoplasma genitalium: should we treat and how? AB - Mycoplasma genitalium is associated with acute and chronic urethritis in men. Existing data on infection in women are limited and inconsistent but suggest that M. genitalium is associated with urethritis, cervicitis, pelvic inflammatory disease, and possibly female infertility. Data are inconclusive regarding the role of M. genitalium in adverse pregnancy outcomes and ectopic pregnancy. Available data suggest that azithromycin is superior to doxycycline in treating M. genitalium infection. However, azithromycin-resistant infections have been reported in 3 continents, and the proportion of azithromycin-resistant M. genitalium infection is unknown. Moxifloxacin is the only drug that currently seems to uniformly eradicate M. genitalium. Detection of M. genitalium is hampered by the absence of a commercially available diagnostic test. Persons with persistent pelvic inflammatory disease or clinically significant persistent urethritis or cervicitis should be tested for M. genitalium, if possible. Infected persons who have not previously received azithromycin should receive that drug. Persons in whom azithromycin therapy fails should be treated with moxifloxicin. PMID- 22080268 TI - Cervical cancer screening among women who attend sexually transmitted diseases (STD) clinics: background paper for 2010 STD Treatment Guidelines. AB - BACKGROUND: In April 2008, experts reviewed updates on sexually transmitted disease (STD) prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. This included a review of cervical cancer screening in the STD clinical setting. METHODS: Key questions were identified with assistance from an expert panel. Reviews of the literature were conducted using the PubMed computerized database and shared with the panel. Updated information was incorporated in the 2010 CDC STD Treatment Guidelines. RESULTS: We recommend that STD clinics offering cervical screening services screen and treat women according to guidelines by the American College of Obstetrics and Gynecology, the American Cancer Society, the US Preventive Services Task Force, and the American Society for Colposcopists and Cervical Pathologists. New to the 2010 guidelines are higher age for initiating cervical screening (age >= 21 years) and less frequent intervals of screening (at least every 3 years). New recommendations include new technologies, such as liquid-based cytology and high-risk human papillomavirus (HPV) DNA tests. Liquid based technologies are not recommended over conventional testing. HPV DNA tests are recommended as adjunct tests and with new indications for use in cervical screening and management. Stronger recommendations were issued for STD clinics offering cervical screening services to have protocols in place for follow-up of test results and referral (eg, colposcopy). CONCLUSIONS: Important additions to the 2010 STD Treatment Guidelines include information on updated algorithms for screening and management of women and recommendations for use of liquid-based cytology and high-risk HPV testing. PMID- 22080270 TI - Centers for Disease Control and Prevention Sexually Transmitted Disease Treatment Guidelines. PMID- 22080269 TI - Trichomonas vaginalis genital infections: progress and challenges. AB - Trichomonas vaginalis (TV) infection is the most prevalent curable sexually transmitted infection in the United States and worldwide. Most TV infections are asymptomatic, and the accurate diagnosis of this infection has been limited by lack of sufficiently sensitive and specific diagnostic tests, particularly for men. To provide updates for the 2010 Centers for Disease Control and Prevention's Sexually Transmitted Diseases Treatment Guidelines, a PubMed search was conducted of all TV literature published from 9 January 2004 through 24 September 2008. Approximately 175 pertinent abstracts and articles were reviewed and discussed with national experts. This article describes advances in TV diagnostics which have led to an improved understanding of the epidemiology of this pathogen, as well as potential biologic and epidemiological interactions between TV and human immunodeficiency virus (HIV). New data on treatment outcomes, metronidazole resistant TV, management of nitroimidazole-allergic patients, frequency of recurrent TV infection following treatment, and screening considerations for TV in certain populations are also presented. PMID- 22080272 TI - Sexually transmitted diseases in men who have sex with men. AB - Men who have sex with men (MSM) have increased rates of human immunodeficiency virus (HIV) infection and sexually transmitted diseases (STDs) compared with demographically matched controls. The reasons for the disproportionate infection burden are complex, including biological, behavioral, and sociocultural factors. HIV and syphilis may often be coprevalent among MSM. The use of nucleic acid amplification testing has enhanced the ability to detect frequently asymptomatic gonococcal and chlamydial infections of the rectum and other sites. Lymphogranuloma proctitis outbreaks among MSM were noted in the developed world several years ago but have not been common recently. MSM are at increased risk for viral hepatitis and anal human papillomavirus disease. Preventive interventions include vaccination for the former and anal cytologic screening for the latter. Because of the diverse ways in which MSM may be exposed to STDs, it is essential for clinicians to obtain a thorough sexual history in a culturally competent manner. PMID- 22080273 TI - Sexually transmitted infections among women who have sex with women. AB - Women who have sex with women (WSW) are a diverse group with variations in sexual identity, sexual behaviors, sexual practices, and risk behaviors. WSW are at risk of acquiring bacterial, viral, and protozoal sexually transmitted infections (STIs) from current and prior partners, both male and female. Bacterial vaginosis is common among women in general and even more so among women with female partners. WSW should not be presumed to be at low or no risk for STIs based on sexual orientation, and reporting of same-sex behavior by women should not deter providers from considering and performing screening for STIs, including chlamydia, in their clients according to current guidelines. Effective delivery of sexual health services to WSW requires a comprehensive and open discussion of sexual and behavioral risks, beyond sexual identity, between care providers and their female clients. PMID- 22080274 TI - Diagnosis and management of uncomplicated Chlamydia trachomatis infections in adolescents and adults: summary of evidence reviewed for the 2010 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines. AB - In preparation for the 2010 Centers for Disease Control and Prevention (CDC) Sexually Transmitted Diseases (STD) Treatment Guidelines, the CDC convened an advisory group in April 2009 to examine recent abstracts and published literature addressing the diagnosis and management of STDs. This article summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis infection in adolescents and adults that were considered in development of the 2010 CDC STD Treatment Guidelines. The evidence reviewed primarily focused on specimen types used for nucleic acid amplification testing for chlamydia diagnosis, considerations in screening men for chlamydia and repeat testing after infected men receive treatment, and the natural history of chlamydia. PMID- 22080271 TI - Interventions to prevent sexually transmitted infections, including HIV infection. AB - The Centers for Disease Control and Prevention (CDC) Sexually Transmitted Disease (STD) Treatment Guidelines were last updated in 2006. To update the "Clinical Guide to Prevention Services" section of the 2010 CDC STD Treatment Guidelines, we reviewed the recent science with reference to interventions designed to prevent acquisition of STDs, including human immunodeficiency virus (HIV) infection. Major interval developments include (1) licensure and uptake of immunization against genital human papillomavirus, (2) validation of male circumcision as a potent prevention tool against acquisition of HIV and some other sexually transmitted infections (STIs), (3) failure of a promising HIV vaccine candidate to afford protection against HIV acquisition, (4) encouragement about the use of antiretroviral agents as preexposure prophylaxis to reduce risk of HIV and herpes simplex virus acquisition, (5) enhanced emphasis on expedited partner management and rescreening for persons infected with Chlamydia trachomatis and Neisseria gonorrhoeae, (6) recognition that behavioral interventions will be needed to address a new trend of sexually transmitted hepatitis C among men who have sex with men, and (7) the availability of a modified female condom. A range of preventive interventions is needed to reduce the risks of acquiring STI, including HIV infection, among sexually active people, and a flexible approach targeted to specific populations should integrate combinations of biomedical, behavioral, and structural interventions. These would ideally involve an array of prevention contexts, including (1) communications and practices among sexual partners, (2) transactions between individual clients and their healthcare providers, and (3) comprehensive population-level strategies for prioritizing prevention research, ensuring accurate outcome assessment, and formulating health policy. PMID- 22080275 TI - Chlamydial and gonococcal infections in infants and children. AB - The recommendations for the 2010 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines in regard to diagnosis and treatment of gonococcal and Chlamydia trachomatis infections in infants and children are essentially the same as the 2006 guidelines. There are no new data on the diagnosis or treatment of neonatal chlamydial or gonococcal infections. New data on the efficacy of neonatal ocular prophylaxis are limited. Two recent studies from Iran and Brazil suggest that povidone-iodine may not be effective for prevention of chlamydial or gonococcal ophthalmia. Prenatal screening and treatment of pregnant women, which has been demonstrated to be very effective for the prevention of neonatal gonococcal ophthalmia, is the most effective strategy for preventing neonatal chlamydial infection. PMID- 22080276 TI - Factors that influence mammography use and breast cancer detection among Mexican American and African-American women. AB - OBJECTIVE: This study examined factors that influence mammography use and breast cancer detection, including education, health insurance, and acculturation, among Mexican-American (MA) and African-American (AA) women. METHODS: The study included 670 breast cancer cases (388 MAs and 282 AAs), aged 40-86 years at diagnosis. Data on mammography use, detection, and delay in seeking care were collected via questionnaires and medical records. Using a language-based bidimensional acculturation measure, MAs were classified as English-dominant (n = 67), bilingual (n = 173), and Spanish-dominant (n = 148). Mammography prior to diagnosis was assessed by racial/ethnic acculturation subgroup using logistic regression. RESULTS: In age-adjusted models, mammography use was non significantly lower among English-dominant (OR = 0.84; 95% CI: 0.45-1.59) and bilingual (OR = 0.86; 95% CI: 0.55-1.35) MAs and significantly lower among Spanish-dominant MAs (OR = 0.53; 95% CI: 0.34-0.83) than among AA women. After adjustment for education or insurance, there was no difference in mammography use by race/ethnicity and acculturation subgroup. Despite high self-reported mammography use (75%), a large proportion of cases reported self-detection (59%) and delay in seeking care >90 days (17%). CONCLUSIONS: These findings favor promoting culturally appropriate messaging about the benefits and limitations of mammography, education about breast awareness, and prompt reporting of findings to a health professional. PMID- 22080277 TI - Dual effect of short interval between first and second birth on ductal breast cancer risk in Finland. AB - OBJECTIVE: A short interval between the first and second birth was associated with an increased risk of advanced ductal breast cancer among women with 5+ childbirths in our previous study. We now evaluated the significance of this risk factor and its relation to the age at first birth among mothers with 2-4 children. METHODS: The cohort of 190,949 Finnish women with 2-4 children comprised 3,834 women with ductal breast cancer diagnosed before 2009. Conditional logistic regression for case-control design nested within the cohort was used to estimate proportional hazard ratios (HR) associated with the birth interval. Controls were matched for age and number of children. Age at the first birth and the interval from the last birth to cancer were co-variables. RESULTS: Among women with the first birth <30 years, the HR of advanced ductal breast cancer at 50+ years for a short (<1.5 years) versus long (>3 years) interval between the first and second birth was 0.48 (95% Confidence Interval 0.33-0.70). Among women with the first birth at 30+ years, the HR of this cancer type diagnosed before the age of 50 years for a short versus long interval between the first and second birth was 5.83 (95% CI 2.30-14.8). CONCLUSION: The interval between first and second birth strongly influences the risk of ductal breast cancer. Because second pregnancy soon after the first one decreased the risk of ductal breast cancer in young primiparas but increased the risk in older primiparas, it is likely that in such circumstances second pregnancy continues the actions initiated by the first pregnancy/breast-feeding. PMID- 22080278 TI - Associations of birth weight and physical activity with sex steroids in preschool Japanese children. AB - PURPOSE: We aimed to assess the association of body size at birth or physical activity with sex steroid levels, independent of body mass among young children. METHODS: The cross-sectional study was conducted in 2006. Subjects were 230 boys and 198 girls, aged 3-6 years. Birth weight was based on parents' reports. Questions about physical activity focused on outdoor playtime. Urinary estrone, estradiol, testosterone, and 5-androstene-3beta,17alpha diol (3beta,17alpha-AED) levels were measured by liquid chromatography-electrospray ionization tandem mass spectrometry. Urinary dehydroepiandrosterone level was measured with a radioimmunoassay. RESULTS: After adjustments for age and BMI, girls with lower birth weight had higher testosterone (trend p = 0.038) and 3beta,17alpha-AED (trend p = 0.028). Girls with low birth weight and high birth weight had higher estrone (p = 0.014) and estradiol (p = 0.074) than those who had middle birth weight. Boys who were physically active had lower testosterone (p = 0.028) and 3beta,17alpha-AED (p = 0.003) than those who were not active. Girls who were physically active had lower estrone (p = 0.015). CONCLUSIONS: Sex steroid levels in childhood might be affected by body size at birth or by physical activity during childhood. These effects might differ by sex. PMID- 22080279 TI - Anion receptor chemistry: highlights from 2010. AB - This critical review covers advances in anion complexation in the year 2010. The review covers both organic and inorganic systems and also highlights the applications to which anion receptors can be applied such as sensing, anion transport, control of molecular motion and gelation (179 references). PMID- 22080281 TI - Multifunctional ferritin cage nanostructures for fluorescence and MR imaging of tumor cells. AB - Bionanoparticles and nanostructures have attracted increasing interest as versatile and promising tools in many applications including biosensing and bioimaging. In this study, to image and detect tumor cells, ferritin cage-based multifunctional hybrid nanostructures were constructed that: (i) displayed both the green fluorescent protein and an Arg-Gly-Asp peptide on the exterior surface of the ferritin cages; and (ii) incorporated ferrimagnetic iron oxide nanoparticles into the ferritin interior cavity. The overall architecture of ferritin cages did not change after being integrated with fusion proteins and ferrimagnetic iron oxide nanoparticles. These multifunctional nanostructures were successfully used as a fluorescent imaging probe and an MRI contrast agent for specifically probing and imaging alpha(v)beta(3) integrin upregulated tumor cells. The work provides a promising strategy for tumor cell detection by simultaneous fluorescence and MR imaging. PMID- 22080280 TI - Acidophilic bacteria and archaea: acid stable biocatalysts and their potential applications. AB - Acidophiles are ecologically and economically important group of microorganisms, which thrive in acidic natural (solfataric fields, sulfuric pools) as well as artificial man-made (areas associated with human activities such as mining of coal and metal ores) environments. They possess networked cellular adaptations to regulate pH inside the cell. Several extracellular enzymes from acidophiles are known to be functional at much lower pH than the cytoplasmic pH. Enzymes like amylases, proteases, ligases, cellulases, xylanases, alpha-glucosidases, endoglucanases, and esterases stable at low pH are known from various acidophilic microbes. The possibility of improving them by genetic engineering and directed evolution will further boost their industrial applications. Besides biocatalysts, other biomolecules such as plasmids, rusticynin, and maltose-binding protein have also been reported from acidophiles. Some strategies for circumventing the problems encountered in expressing genes encoding proteins from extreme acidophiles have been suggested. The investigations on the analysis of crystal structures of some acidophilic proteins have thrown light on their acid stability. Attempts are being made to use thermoacidophilic microbes for biofuel production from lignocellulosic biomass. The enzymes from acidophiles are mainly used in polymer degradation. PMID- 22080282 TI - Use of end-cutting needles in ultrasound-guided biopsy of neck lesions. AB - The management of a neck mass is dictated by its nature, location and extent. Pathological diagnosis by fine needle aspiration cytology (FNAC) or core biopsy is often required before proceeding to definitive treatment. It is not uncommon for the cytology result to come back as inadequate for various reasons. The unique design of the end-cutting biopsy needle in our experience makes it a good choice for use in obtaining both transcutaneous and intraoral biopsy under ultrasound guidance of neck lesions and serves as a useful alternative or adjunct to FNAC. Although there is, as yet, only a limited evidence base about end cutting in comparison to side-cutting needles, they carry several potential advantages. KEY POINTS: End-cutting needles are safe to use for lesions close to vital structures. End-cutting needles yield sufficient tissue samples in a single pass. End-cutting biopsy needles are a useful adjunct to FNAC. PMID- 22080283 TI - Comparison of joint designs for laser welding of cast metal plates and wrought wires. AB - The purpose of the present study was to compare joint designs for the laser welding of cast metal plates and wrought wire, and to evaluate the welded area internally using X-ray micro-focus computerized tomography (micro-CT). Cast metal plates (Ti, Co-Cr) and wrought wires (Ti, Co-Cr) were welded using similar metals. The specimens were welded using four joint designs in which the wrought wires and the parent metals were welded directly (two designs) or the wrought wires were welded to the groove of the parent metal from one or both sides (n = 5). The porosity and gap in the welded area were evaluated by micro-CT, and the maximum tensile load of the welded specimens was measured with a universal testing machine. An element analysis was conducted using an electron probe X-ray microanalyzer. The statistical analysis of the results was performed using Bonferroni's multiple comparisons (alpha = 0.05). The results included that all the specimens fractured at the wrought wire when subjected to tensile testing, although there were specimens that exhibited gaps due to the joint design. The wrought wires were affected by laser irradiation and observed to melt together and onto the filler metal. Both Mo and Sn elements found in the wrought wire were detected in the filler metal of the Ti specimens, and Ni was detected in the filler metal of the Co-Cr specimens. The four joint designs simulating the designs used clinically were confirmed to have adequate joint strength provided by laser welding. PMID- 22080285 TI - One-step synthesis of amino-functionalized fluorescent carbon nanoparticles by hydrothermal carbonization of chitosan. AB - Highly amino-functionalized fluorescent carbon nanoparticles (CNPs) were fabricated by hydrothermal carbonization of chitosan at a mild temperature. They were applied to bioimaging of human lung adenocarcinoma A549 cells, showing low cytotoxicity and excellent biocompatibility. PMID- 22080284 TI - Creating an oversight infrastructure for electronic health record-related patient safety hazards. AB - Electronic health records (EHRs) have potential quality and safety benefits. However, reports of EHR-related safety hazards are now emerging. The Office of the National Coordinator for Health Information Technology recently sponsored an Institute of Medicine committee to evaluate how health information technology use affects patient safety. In this article, we propose the creation of a national EHR oversight program to provide dedicated surveillance of EHR-related safety hazards and to promote learning from identified errors, close calls, and adverse events. The program calls for data gathering, investigation/analysis, and regulatory components. The first 2 functions will depend on institution-level EHR safety committees that will investigate all known EHR-related adverse events and near-misses and report them nationally using standardized methods. These committees should also perform routine safety self-assessments to proactively identify new risks. Nationally, we propose the long-term creation of a centralized, nonpartisan board with an appropriate legal and regulatory infrastructure to ensure the safety of EHRs. We discuss the rationale of the proposed oversight program and its potential organizational components and functions. These include mechanisms for robust data collection and analyses of all safety concerns using multiple methods that extend beyond reporting, multidisciplinary investigation of selected high-risk safety events, and enhanced coordination with other national agencies to facilitate broad dissemination of hazards information. Implementation of this proposed infrastructure can facilitate identification of EHR-related adverse events and errors and potentially create a safer and more effective EHR-based health care delivery system. PMID- 22080287 TI - Protein growth factors and cytokines are typically thought to drive the proliferative/invasive/survival hallmarks of cancer. Preface. PMID- 22080286 TI - Antimicrobial and cell-penetrating peptides induce lipid vesicle fusion by folding and aggregation. AB - According to their distinct biological functions, membrane-active peptides are generally classified as antimicrobial (AMP), cell-penetrating (CPP), or fusion peptides (FP). The former two classes are known to have some structural and physicochemical similarities, but fusogenic peptides tend to have rather different features and sequences. Nevertheless, we found that many CPPs and some AMPs exhibit a pronounced fusogenic activity, as measured by a lipid mixing assay with vesicles composed of typical eukaryotic lipids. Compared to the HIV fusion peptide (FP23) as a representative standard, all designer-made peptides showed much higher lipid-mixing activities (MSI-103, MAP, transportan, penetratin, Pep1). Native sequences, on the other hand, were less fusogenic (magainin 2, PGLa, gramicidin S), and pre-aggregated ones were inactive (alamethicin, SAP). The peptide structures were characterized by circular dichroism before and after interacting with the lipid vesicles. A striking correlation between the extent of conformational change and the respective fusion activities was found for the series of peptides investigated here. At the same time, the CD data show that lipid mixing can be triggered by any type of conformation acquired upon binding, whether alpha-helical, beta-stranded, or other. These observations suggest that lipid vesicle fusion can simply be driven by the energy released upon membrane binding, peptide folding, and possibly further aggregation. This comparative study of AMPs, CPPs, and FPs emphasizes the multifunctional aspects of membrane active peptides, and it suggests that the origin of a peptide (native sequence or designer-made) may be more relevant to define its functional range than any given name. PMID- 22080288 TI - An ONIOM investigation on anion recognition of alkali-metal complexes with diurea calix[4]arene receptor. AB - The ONIOM(B3LYP/6-31G(d):AM1) optimized structures of complexes of diurea calix[4]arene receptor (L) with alkali metals Li(+), Na(+) and K(+) and their complexes with halide ions F(-), Cl(-), Br(-), oxygen-containing anions HCO(3)( ), HSO(4)(-) and CH(3)COO(-) ions were obtained. Binding energies and thermodynamic properties of complex receptors LiL(+), NaL(+) and KL(+) with these anions were determined. The binding stabilities according to binding energies of LiL(+), NaL(+) and KL(+) associated with anions computed either at the ZPVE corrected ONIOM(B3LYP/6-31G(d):AM1) or BSSE-corrected B3LYP/6-31 + G(d,p)//ONIOM(B3LYP/6-31G(d):AM1) are in the same order: F(-) >> CH(3)COO(-) ~ HCO(3)(-) > Br(-) ~ HSO(4)(-) ~ Cl(-). All the receptors LiL(+), NaL(+) and KL(+) were found to be selective toward fluoride ion. PMID- 22080289 TI - Empowering international canine inherited disorder management. AB - The mapping of the canine genome and the study of canine breed genomic architecture has revolutionized the discovery of genetic tests for inherited disorders in dogs. As the genetics underlying complex disorders are revealed, canine breeders and their registering organisations will be required to understand genetics in a much more sophisticated way. To facilitate the management of genetic disorders in the era of new complex information, we consider how best to apply the results of new research and analytical techniques to benefit the wider canine breeding community with the aims of improving canine health and maintaining benevolent genetic diversity. If this is not done, there is a serious risk that expensive and valuable genetic research will remain unused or be misused to the detriment of breeds. In this review, we make a case for the formation of an international organisation that will exist as a central repository for breed-based genetic analysis and information sharing. This organisation ("Inter-Dog") could be modelled on a similar organisation that is monitoring genetic improvement of dairy cattle. The formation of such an organisation will require the collaboration of international kennel management organisations, researchers, and agencies offering genetic testing services. PMID- 22080290 TI - Fabrication of multi-level carbon nanotube arrays with adjustable patterns. AB - Multi-level carbon nanotube (CNT) arrays with adjustable patterns were prepared by a combination of the breath figure (BF) process and chemical vapor deposition. Polystyrene-b-poly(acrylic acid)/ferrocene was dissolved in carbon disulfide and cast onto a Si substrate covered with a transmission electron microscope grid in saturated relative humidity. A two-level microporous hybrid film with a block copolymer skeleton formed on the substrate after evaporation of the organic solvent and water. One level of ordered surface features originates from the contour of the hard templates; while the other level originates from the condensation of water droplets (BF arrays). Ultraviolet irradiation effectively cross-linked the polymer matrix and endowed the hybrid film with improved thermal stability. In the subsequent pyrolysis, the incorporated ferrocene in the hybrid film was oxidized and turned the polymer skeleton into the ferrous inorganic micropatterns. Either the cross-linked hybrid film or the ferrous inorganic micropatterns could act as a template to grow the multi-level CNT patterns, e.g. isolated and honeycomb-structured CNT bundle arrays perpendicular to the substrate. PMID- 22080291 TI - User evaluation of an innovative digital reading room. AB - Reading room design can have a major impact on radiologists' health, productivity, and accuracy in reading. Several factors must be taken into account in order to optimize the work environment for radiologists. Further, with the advancement in imaging technology, clinicians now have the ability to view and see digital exams without having to interact with radiologists. However, it is important to design components that encourage and enhance interactions between clinicians and radiologists to increase patient safety, and to combine physician and radiologist expertise. The present study evaluates alternative workstations in a real-world testbed space, using qualitative data (users' perspectives) to measure satisfaction with the lighting, ergonomics, furniture, collaborative spaces, and radiologist workstations. In addition, we consider the impact of the added collaboration components of the future reading room design, by utilizing user evaluation surveys to devise baseline satisfaction data regarding the innovative reading room environment. PMID- 22080292 TI - A flexible database architecture for mining DICOM objects: the DICOM data warehouse. AB - Digital Imaging and Communications in Medicine (DICOM) has brought a very high level of standardization to medical images, allowing interoperability in many cases. However, there are still challenges facing the informaticist attempting to data mine DICOM objects. Images (and other objects) from different vintage equipment will encompass different levels of the standard, and there are also proprietary "shadow" tags to be aware of. The database architecture described herein "flattens" such differences by compiling a knowledge base of specific DICOM implementations and mapping variable data elements to a common lexicon for subsequent queries. The project is open sourced, built on open infrastructure, and is available at GitHub. PMID- 22080293 TI - Reduced ventricular proarrhythmic potential of the novel combined ion-channel blocker AZD1305 versus dofetilide in dogs with remodeled hearts. AB - BACKGROUND: AZD1305 is an investigational antiarrhythmic agent for management of atrial fibrillation. It blocks various cardiac ion currents at different potencies and has atrial-predominant electrophysiological effects. We investigated the electrophysiological and proarrhythmic effects of AZD1305 versus dofetilide in dogs with chronic complete atrioventricular block and myocardial hypertrophic remodeling. METHODS AND RESULTS: AZD1305 was administered to anesthetized mongrel dogs before and >2 weeks after the induction of atrioventricular block and ventricular and atrial electrophysiological parameters were assessed. In all dogs, the selective I(Kr) blocker dofetilide was used to examine susceptibility to acquired torsades de pointes in chronic atrioventricular block and for comparison. At normal sinus rhythm, AZD1305 increased QT and RR intervals from 290+/-7 to 397+/-15 ms (+37%, P<0.0001) and from 603+/-22 to 778+/-32 ms (+29%, P=0.002), respectively. In the same animals at chronic atrioventricular block, AZD1305 increased the QT interval from 535+/ 28 to 747+/-36 ms (+40%, P<0.0001), similar to the QT prolongation by dofetilide (511+/-22 to 703+/-45 ms [+38%, P<0.0001]). AZD1305 slightly slowed the idioventricular rhythm. Whereas all (n=14) chronic atrioventricular block animals exhibited torsades de pointes on dofetilide, the arrhythmia was induced in only 4 of 11 dogs after AZD1305. Beat-to-beat variability of left-ventricular monophasic action-potential duration increased after dofetilide (2.3+/-0.2 to 6.3+/-0.7 ms; P<0.0001) but not after AZD1305 (2.8+/-0.3 to 3.7+/-0.3 ms; P=0.20) despite similar left-ventricular monophasic-action-potential duration prolongations. CONCLUSIONS: Despite causing similar degrees of repolarization delay as the selective I(Kr) blocker dofetilide, the combined ion-channel blocker AZD1305 induces less repolarization instability and has a lower ventricular proarrhythmic potential in the remodeled dog heart. PMID- 22080294 TI - Responses of growth, photosynthesis and VOC emissions of Pinus tabulaeformis Carr. Exposure to elevated CO2 and/or elevated O3 in an urban area. AB - Responses of growth, photosynthesis and emission of volatile organic compounds of Pinus tabulaeformis exposed to elevated CO(2) (700 ppm) and O(3) (80 ppb) were studied in open top chambers. Elevated CO(2) increased growth, but it did not significantly (p > 0.05) affect net photosynthetic rate, stomatal conductance, chlorophyll content, the maximum quantum yield of photosystem II, or the effective quantum yield of photosystem II electron transport after 90 d of gas exposure. Elevated O(3) decreased growth (by 42.2% in needle weight and 25.8% in plant height), net photosynthetic rate and stomatal conductance after 90 d of exposure, but its negative effects were alleviated by elevated CO(2). Elevated O(3) significantly (p < 0.05) increased the emission rate of volatile organic compounds, which may be a helpful response to protect photosynthetic apparatus against O(3) damage. PMID- 22080295 TI - Light and scanning electron microscopic studies on chromium-induced anemia in a murine model. AB - Blood hemoglobin level, hematocrit value and erythrocyte count were reduced by 17.5, 17.4 and 15.9%, respectively, as compared to the controls, in Swiss mice treated intraperitoneally with hexavalent chromium (4 mg of potassium dichromate per Kg for 5 day per week) for 2 weeks. Echinocytic transformation of 33.8% erythrocytes, as revealed by both light and scanning electron microscopy, indicated the anemia to be hemolytic in nature. Leucopenia was apparent after 2 weeks (mean leucocyte count: 4.91 thousand c mm(-1)), but not 1 week of treatment (mean count: 6.43 thousand c mm(-1)), However, cytochemical studies indicated that chromium did not interfere with iron utilization for hemoglobin synthesis and also, did not cause denaturation of already synthesized hemoglobin. The study hints to the necessity of periodic monitoring of blood in workers of chromium dependent tanneries of Kolkata, India. PMID- 22080296 TI - Subungual exostosis of the fifth toe in children. PMID- 22080297 TI - Necrotizing upper limb fasciitis in a newborn: an uncommon life-threatening event. AB - Necrotizing fasciitis is an uncommon but life-threatening infection in the pediatric population. It is rarely reported in neonates. In these rare cases, the reported origin of infection was the umbilical cord stump, infection due to circumcision, and similar lesions. We hereby report a 3-week-old neonate sustaining necrotizing fasciitis without detectable origin of infection. We describe the clinical course of her illness, the diagnostic process, and eventual surgical intervention. We discuss the importance of awareness to this potentially lethal infectious disease and the need for urgent use of certain imaging modalities and aggressive surgical approach. PMID- 22080298 TI - Comprehensive review of the functional outcome evaluation of clubfoot treatment: a preferred methodology. AB - Treatment outcome has been a focus of interest in those who manage clubfeet. Because of a lack of a common evaluation protocol, it has become necessary to establish a universally recognized quantitative measurement to compare and better understand the treatment outcome. The outcome is not merely morphological and radiographic, but it should also include functional and quality-of-life measurements. In this article, we will outline the most commonly used methods of long-term evaluation for congenital clubfeet and recommend the data collection parameters that are most appropriate for a comprehensive functional analysis. This will begin with pretreatment classifications that are important in prognosticating the results. The physical examinations and plain radiographs in standing position are also two fundamental evaluations of clubfoot. Several outcome evaluations have been published in the literature and may be useful depending on the desired metrics. Gait analysis is an additional useful technical tool for analyzing the motion of the foot and ankle and its relation to the whole body function; pedobarography added to the dynamics of the evaluation. Functional quality-of-life questionnaires are increasing in popularity for measuring the total body functional status and the quality of life. PMID- 22080299 TI - Tumoral calcinosis of the cervical spine and its association with Caffey disease in a 4-month-old boy: case report and review of the literature. AB - Tumoral calcinosis (TC) is a rare condition involving large joints and rarely the spine. It is characterized by calcification and swelling of periarticular tissues. Caffey disease (CD) is defined by recurrent episodes of painful soft tissue swelling and cortical thickening of the underlying bones. It is a self limited disease that occurs in the first year of life. We report the first association of CD and TC of the cervical spine in a 4-month-old boy. We suggest that TC occurred as a consequence of the repetitive reparative process that takes place in CD, adding the latter to the list of diseases that may secondarily produce TC. PMID- 22080300 TI - Immunogenetic Management Software: a new tool for visualization and analysis of complex immunogenetic datasets. AB - Here we describe the Immunogenetic Management Software (IMS) system, a novel web based application that permits multiplexed analysis of complex immunogenetic traits that are necessary for the accurate planning and execution of experiments involving large animal models, including nonhuman primates. IMS is capable of housing complex pedigree relationships, microsatellite-based MHC typing data, as well as MHC pyrosequencing expression analysis of class I alleles. It includes a novel, automated MHC haplotype naming algorithm and has accomplished an innovative visualization protocol that allows users to view multiple familial and MHC haplotype relationships through a single, interactive graphical interface. Detailed DNA and RNA-based data can also be queried and analyzed in a highly accessible fashion, and flexible search capabilities allow experimental choices to be made based on multiple, individualized and expandable immunogenetic factors. This web application is implemented in Java, MySQL, Tomcat, and Apache, with supported browsers including Internet Explorer and Firefox on Windows and Safari on Mac OS. The software is freely available for distribution to noncommercial users by contacting Leslie.kean@emory.edu. A demonstration site for the software is available at http://typing.emory.edu/typing_demo , user name: imsdemo7@gmail.com and password: imsdemo. PMID- 22080301 TI - Controlled nanoporosity of organic aerogels by dispersing clay platelets. AB - A new class of organic-inorganic hybrid aerogels having small pores and narrow pore size distribution are synthesized from well-dispersed clay platelets in water as base catalyst. Clay-catalyzed organic gels have strong advantage in controlling nanopore structure as well as reducing drying shrinkage by reinforcing the organic network with inorganic platelets. PMID- 22080302 TI - Fabrication of SERS-fluorescence dual modal nanoprobes and application to multiplex cancer cell imaging. AB - We report a highly sensitive optical imaging technology using surface-enhanced Raman scattering (SERS)-fluorescence dual modal nanoprobes (DMNPs). Fluorescence microscopy is a well-known imaging technique that shows specific protein distributions within cells. However, most currently available fluorescent organic dyes have relatively weak emission intensities and are rapidly photo-bleached. Thus more sensitive and stable probes are needed. In this work we develop DMNPs, which can be used for both SERS and fluorescence detection. SERS detection is a powerful technique that allows ultrasensitive chemical or biochemical analysis through unlimited multiplexing and single molecule sensitivity. Combining advantages of fluorescence and SERS allows these dual modal nanostructures to be used as powerful probes for novel biomedical imaging. In this work, the fabrication and characterization of the SERS-fluorescence DMNPs and application to biological imaging were investigated using markers CD24 and CD44, which are co expressed in MDA-MB-231 breast cancer cells, as a model system. SERS imaging with DMNPs was found to be a powerful tool to determine the co-localization of CD24 and CD44 in the cell. PMID- 22080303 TI - Evidence for acyl-iron ligation in the active site of [Fe]-hydrogenase provided by mass spectrometry and infrared spectroscopy. AB - [Fe]-hydrogenase catalyzes the reversible heterolytic cleavage of H(2) and stereo specific hydride transfer to the substrate methenyltetrahydromethanopterin in methanogenic archaea. This enzyme contains a unique iron guanylylpyridinol (FeGP) cofactor as a prosthetic group. It has recently been proposed-on the basis of crystal structural analyses of the [Fe]-hydrogenase holoenzyme-that the FeGP cofactor contains an acyl-iron ligation, the first one reported in a biological system. We report here that the cofactor can be reversibly extracted with acids; its exact mass has been determined by electrospray ionization Fourier transform ion cyclotron resonance mass-spectrometry. The measured mass of the intact cofactor and its gas-phase fragments are consistent with the proposed structure. The mass of the light decomposition products of the cofactor support the presence of acyl-iron ligation. Attenuated total reflection infrared spectroscopy of the FeGP cofactor revealed a band near wave number 1700 cm(-1), which was assigned to the C=O (double bond) stretching mode of the acyl-iron ligand. PMID- 22080304 TI - Genetics of canine olfaction and receptor diversity. AB - Olfaction is a particularly important sense in the dog. Humans selected for this capacity during the domestication process, and selection has continued to be employed to enhance this ability. In this review we first describe the different olfactory systems that exist and the different odorant receptors that are expressed in those systems. We then focus on the dog olfactory receptors by describing the olfactory receptor gene repertoire and its polymorphisms. Finally, we discuss the different uses of dog olfaction and the questions that still need to be studied. PMID- 22080305 TI - Family support in prevention programs for children at risk for emotional/behavioral problems. AB - We conducted a review of empirically based prevention programs to identify prevalence and types of family support services within these programs. A total of 238 articles published between 1990 and 2011 that included a family support component were identified; 37 met criteria for inclusion. Following the Institute of Medicine's typology, prevention programs were categorized as universal, selective, or indicated; programs containing more than one prevention level were characterized as multi-level. Family support types included those led by a mental health professional, led by a peer, or team-led. Among the 37 prevention programs reviewed, 27% (n=10) were universal, 41% (n=15) were selective, 16% (n=6) were indicated, and 16% (n=6) were multi-level. The predominant model of family support was professionally led (95%, n=35). Two (n=5%) provided team-led services. None were purely peer-led. In terms of content of family support services, all (100%, n=37) provided instruction/skill build. Information and education was provided by 70% (n=26), followed by emotional support (n=11, 30%) and instrumental or concrete assistance (n=11, 30%). Only 14% (n=5) provided assistance with advocacy. The distribution of models and content of services in prevention studies differ from family support within treatment studies. As family support is likely to be an enduring component of the child and family mental health service continuum, comparative effectiveness studies are needed to inform future development. PMID- 22080306 TI - A QSAR study of radical scavenging antioxidant activity of a series of flavonoids using DFT based quantum chemical descriptors--the importance of group frontier electron density. AB - In a pursuit of electronic level understanding of the antioxidant activity of a series of flavonoids, quantitative structure-activity relationship (QSAR) studies have been carried out using density functional theory (DFT) based quantum chemical descriptors. The best QSAR model have been selected for which the computed square correlation coefficient r(2) = 0.937 and cross-validated squared correlation coefficient q(2) =0.916. The QSAR model indicates that hardness (eta), group electrophilic frontier electron density (F(E)(A)) and group philicity (omega(B)(+)) of individual molecules are responsible for in vitro biological activity. To the best our knowledge, the group electrophilic frontier electron density (F(E)(A)) has been used for the first time to explain the radical scavenging activity (RSA) of flavonoids. The excellent correlation between the RSA and the above mentioned DFT based descriptors lead us to predict new antioxidants having very good antioxidant activity. PMID- 22080307 TI - Hydrothermal pretreatment of sugarcane bagasse using response surface methodology improves digestibility and ethanol production by SSF. AB - Sugarcane bagasse was characterized as a feedstock for the production of ethanol using hydrothermal pretreatment. Reaction temperature and time were varied between 160 and 200 degrees C and 5-20 min, respectively, using a response surface experimental design. The liquid fraction was analyzed for soluble carbohydrates and furan aldehydes. The solid fraction was analyzed for structural carbohydrates and Klason lignin. Pretreatment conditions were evaluated based on enzymatic extraction of glucose and xylose and conversion to ethanol using a simultaneous saccharification and fermentation scheme. SSF experiments were conducted with the washed pretreated biomass. The severity of the pretreatment should be sufficient to drive enzymatic digestion and ethanol yields, however, sugars losses and especially sugar conversion into furans needs to be minimized. As expected, furfural production increased with pretreatment severity and specifically xylose release. However, provided that the severity was kept below a general severity factor of 4.0, production of furfural was below an inhibitory concentration and carbohydrate contents were preserved in the pretreated whole hydrolysate. There were significant interactions between time and temperature for all the responses except cellulose digestion. The models were highly predictive for cellulose digestibility (R (2) = 0.8861) and for ethanol production (R (2) = 0.9581), but less so for xylose extraction. Both cellulose digestion and ethanol production increased with severity, however, high levels of furfural generated under more severe pretreatment conditions favor lower severity pretreatments. The optimal pretreatment condition that gave the highest conversion yield of ethanol, while minimizing furfural production, was judged to be 190 degrees C and 17.2 min. The whole hydrolysate was also converted to ethanol using SSF. To reduce the concentration of inhibitors, the liquid fraction was conditioned prior to fermentation by removing inhibitory chemicals using the fungus Coniochaeta ligniaria. PMID- 22080308 TI - Anemia, iron deficiency, and stress fractures in female combatants during 16 months. AB - Yanovich, R, Merkel, D, Israeli, E, Evans, RK, Erlich, T, and Moran, DS. Anemia, iron deficiency, and stress fractures in female combatants during 16 months. J Strength Cond Res 25(12): 3412-3421, 2011-The purpose of this study is to evaluate the hematological profile of military recruits in different settings and training programs and to investigate the link between anemia and iron deficiency with stress fracture (SF) occurrence. We surveyed 3 groups of recruits for 16 months: 221 women (F) and 78 men (M) from 3 different platoons of a gender integrated combat battalion and a control group (CF) of 121 female soldiers from a noncombat unit. Data were fully collected upon induction and at 4 and 16 months from 48F, 21M, and 31CF. Blood tests, anthropometry, physical aerobic fitness, and SF occurrence were evaluated. On induction day, 18.0 and 19.0% of F and CF were found to be anemic, and 61.4 and 50.9%, respectively, were found to have iron deficiency, whereas 7.7% of M were found to be anemic and 10.2% iron deficient. During the 4 months of army basic training (ABT), anemia and iron deficiency prevalence did not change significantly in any group. After 16-months, anemia prevalence decreased by 8% among F and CF and abated in M. Iron deficiency was prevalent in 50.0, 59.4, and 18.8% of F, CF, and M, respectively. Stress fractures were diagnosed in 14 F during ABT, and they had a significantly higher prevalence (p < 0.05) of anemia and iron deficiency anemia compared to F without SFs. The observed link between anemia and iron deficiency on recruitment day and SFs suggests the importance of screening female combat recruits for these deficiencies. To minimize the health impact of army service on female soldiers, preventative measures related to anemia and iron deficiency should be administered. Further research is needed for evaluating the influence of low iron in kosher meat as a possible explanation for the high prevalence of iron deficiency among young Israeli recruits. PMID- 22080309 TI - Core stability exercises in individuals with and without chronic nonspecific low back pain. AB - Marshall, PWM, Desai, I, and Robbins, DW. Core stability exercises in individuals with and without chronic nonspecific low back pain. J Strength Cond Res 25(12): 3404-3411, 2011-The aim of this study was to measure trunk muscle activity during several commonly used exercises in individuals with and without low back pain (LBP). Abdominal bracing was investigated as an exercise modification that may increase the acute training stimulus. After an initial familiarization session, 10 patients with LBP and 10 matched controls performed 5 different exercises (quadruped, side bridge, modified push-up, squat, shoulder flexion) with and without abdominal bracing. Trunk muscle activity and lumbar range of motion (LROM) were measured during all exercises. Muscle activity was measured bilaterally during each exercise from rectus abdominis (RA), external obliques (EO), and lumbar erector spinae (ES) with pairs of surface electrodes. Recorded signals were normalized to a percentage of maximal voluntary contractions performed for each muscle. The ES activity was lower for the LBP group during the quadruped (p < 0.05) and higher for RA and EO during the side bridge (p < 0.001), compared to for the healthy controls. Higher muscle activity was observed across exercises in an inconsistent pattern when abdominal bracing was used during exercise. The LROM was no different between groups for any exercise. The lack of worsening of symptoms in the LBP group and similar LROM observed between groups suggest that all exercises investigated in this study are of use in rehabilitating LBP patients. The widespread use of abdominal bracing in clinical practice, whether it be for patients with LBP or healthy individuals, may not be justified unless symptoms of spinal instability are identified. PMID- 22080310 TI - Reliability of performance velocity for jump squats under feedback and nonfeedback conditions. AB - Randell, AD, Cronin, JB, Keogh, JWL, Gill, ND, and Pedersen, MC. Reliability of performance velocity for jump squats under feedback and nonfeedback conditions. J Strength Cond Res 25(12): 3514-3518, 2011-Advancements in the monitoring of kinematic and kinetic variables during resistance training have resulted in the ability to continuously monitor performance and provide feedback during training. If equipment and software can provide reliable instantaneous feedback related to the variable of interest during training, it is thought that this may result in goal-oriented movement tasks that increase the likelihood of transference to on field performance or at the very least improve the mechanical variable of interest. The purpose of this study was to determine the reliability of performance velocity for jump squats under feedback and nonfeedback conditions over 3 consecutive training sessions. Twenty subjects were randomly allocated to a feedback or nonfeedback group, and each group performed a total of 3 "jump squat" training sessions with the velocity of each repetition measured using a linear position transducer. There was less change in mean velocities between sessions 1-2 and sessions 2-3 (0.07 and 0.02 vs. 0.13 and -0.04 m.s), less random variation (TE = 0.06 and 0.06 vs. 0.10 and 0.07 m.s) and greater consistency (intraclass correlation coefficient = 0.83 and 0.87 vs. 0.53 and 0.74) between sessions for the feedback condition as compared to the nonfeedback condition. It was concluded that there is approximately a 50-50 probability that the provision of feedback was beneficial to the performance in the squat jump over multiple sessions. It is suggested that this has the potential for increasing transference to on-field performance or at the very least improving the mechanical variable of interest. PMID- 22080311 TI - Skeletal mass in adolescent male athletes and nonathletes: relationships with high-impact sports. AB - Dias Quiterio, AL, Canero, EA, Baptista, FM, and Sardinha, LB. Skeletal mass in adolescent male athletes and nonathletes: relationships with high-impact sports. J Strength Cond Res 25(12): 3439-3447, 2011-This study examined the relationships between the practice of different categories of sports (high-impact vs. nonimpact) and bone status in adolescent male athletes and investigated differences from an age-matched control group. A total of 54 adolescent male athletes and 26 adolescent nonathletes were evaluated. Bone mineral density, bone mineral content (BMC), and bone area at the whole-body, limbs, and lumbar spine were determined by dual-energy x-ray absorptiometry, along with total and regional fat-free mass and body fat. The high-impact group included 34 athletes: 9 gymnasts, 18 basketball players, and 7 handball players (age: 15.7 +/- 1.6 years; weight: 72.0 +/- 15.0 kg; height: 178.5 +/- 12.5 cm). The nonimpact group consisted of 20 swimmers (age: 16.4 +/- 2.5 years; weight: 66.9 +/- 10.4 kg; height: 173.7 +/- 10.9 cm). The nonathletic control group included 26 male adolescents (age: 15.9 +/- 2.8 years; weight: 64.7 +/- 16.3 kg; height: 168.6 +/- 15.1 cm). No differences were observed between the nonimpact and the control group in all bone variables, before and after adjustments for maturation level, body weight, and height (p > 0.05). After adjustments for these variables, the high-impact group displayed greater bone mass in most of the measured sites when compared to the other 2 groups (p < 0.001). Subjects in the nonimpact group showed lower values of BMC, particularly in the lower limbs, than both the high impact and the nonathletic control groups (p < 0.05) after adjustments for maturation, high, and fat-free mass. This study reinforces the positive associations between high-impact physical activities and skeletal health in adolescent boys. PMID- 22080312 TI - Improvements in metabolic and neuromuscular fitness after 12-week bodypump(r) training. AB - Greco, CC, Oliveira, AS, Pereira, MP, Figueira, TR, Ruas, VD, Goncalves, M, and Denadai, BS. Improvements in metabolic and neuromuscular fitness after 12-week Bodypump(r) training. J Strength Cond Res 25(12): 3422-3431, 2011-The purpose of this study was to evaluate the effects of a 12-week group fitness training program (Bodypump(r)) on anthropometry, muscle strength, and aerobic fitness. Nineteen women (21.4 +/- 2.0 years old) were randomly assigned to a training group (n = 9) and to a control group (n = 10). We show that this training program improved the 1 repetition maximum squats by 33.1% (p < 0.001) and the maximal isometric voluntary contraction (MVC) by 13.6% (p < 0.05). Additionally, decreases in knee extensor electromyographic activity during the MVC (30%, p < 0.01) and during the squats (15%, p < 0.05) and lunges of a simulated Bodypump(r) session were observed after the training. Concomitantly, blood lactate and heart rate after squats of a simulated Bodypump(r) session were decreased by 33 and 7% (p < 0.05), respectively. Body mass, body fat, and the running velocity at the onset of blood lactate accumulation did not change significantly in response to this training program. We conclude that Bodypump(r) training improves muscular strength and decreases metabolic stress during lower limb exercises. However, no significant improvements in running aerobic fitness nor in body mass and body fat were observed. Practitioners of Bodypump(r) training may benefit from the increased muscular strength and the decreased muscular fatigability during exercise tasks whose motor patterns are related to those involved in this training program. However, these functional gains do not seem to be transferable into running aerobic fitness. PMID- 22080313 TI - Finishers and nonfinishers in the 'Swiss Cycling Marathon ' to qualify for the 'Race Across America '. AB - Knechtle, B, Knechtle, P, Rust, CA, Rosemann, T, and Lepers, R. Finishers and nonfinishers in the 'Swiss Cycling Marathon' to qualify for the 'Race across America.' J Strength Cond Res 25(12): 3257-3263, 2011-We compared the characteristics of prerace anthropometry, previous experience, and training and support during the race in 39 finishers and 37 nonfinishers in the 'Swiss Cycling Marathon,' over 720 km. In this race, the cyclists intended to qualify for the 'Race across America,' the longest nonstop cycling race in the World from the West to the East of the USA. Finishers in the 'Swiss Cycling Marathon' had a lower body mass, a lower body mass index, lower circumferences of upper arm and thigh, a lower percent body fat, completed more weekly training units, covered more kilometers in the longest training ride, rode at a faster speed during training, rode more kilometers per week and for more hours, had more previous finishes in the 'Swiss Cycling Marathon' and a lighter race bike compared to the nonfinishers. In the bivariate analysis, the cycling distance per training unit (r = 0.37), the duration per training unit (r = 0.44), the speed per training unit (r = -0.59), using nutrition provided by the organizer (r = 0.50), and using own nutrition (r = 0.49) during the race were significantly and positively associated with race time. For practical applications, anthropometric characteristics such as a low body mass or low body fat were not related to race time, whereas training characteristics and nutrition during the race were associated with race time. The key to a successful finish in an ultraendurance cycling race such as the 'Swiss Cycling Marathon' seems a high speed in training and an appropriate nutrition during the race. PMID- 22080314 TI - Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise. AB - Rahimi, R. Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise. J Strength Cond Res 25(12): 3448-3455, 2011-Creatine (Cr), or methyl guanidine-acetic acid, can be either ingested from exogenous sources, such as fish or meat, or produced endogenously by the body, primarily in the liver. It is used as an ergogenic aid to improve muscle mass, strength, and endurance. Heretofore, Cr's positive therapeutic benefits in various oxidative stress-associated diseases have been reported in the literature and, recently, Cr has also been shown to exert direct antioxidant effects. Therefore, the purpose of this study was to investigate the effects of an acute bout of resistance exercise (RE) on oxidative stress response and oxidative DNA damage in male athletes and whether supplementation with Cr could negate any observed differences. Twenty-seven resistance-trained men were randomly divided into a Cr supplementation group (the Cr group [21.6 +/- 3.6 years], taking 4 * 5 g Cr monohydrate per day) or a placebo (PL) supplementation group (the PL group [21.2 +/- 3.2 years], taking 4 * 5 g maltodextrin per day). A double-blind research design was employed for a 7-day supplementation period. Before and after the seventh day of supplementation, the subjects performed an RE protocol (7 sets of 4 exercises using 60-90 1 repetition maximum) in the flat pyramid loading pattern. Blood and urine samples taken before, immediately, and 24-hour postexercise were analyzed for plasma malondialdehyde (MDA) and urinary 8 hydroxy-2-deoxyguanosine (8-OHdG) excretion. Before the supplementation period, a significant increase in the urinary 8-OHdG excretion and plasma MDA levels was observed after RE. The Cr supplementation induces a significant increase in athletics performance, and it attenuated the changes observed in the urinary 8 OHdG excretion and plasma MDA. These results indicate that Cr supplementation reduced oxidative DNA damage and lipid peroxidation induced by a single bout of RE. PMID- 22080315 TI - Exertional rhabdomyolysis in an adolescent athlete during preseason conditioning: a perfect storm. AB - Cleary, MA, Sadowski, KA, Lee, SY-C, Miller, GL, and Nichols, AW. Exertional rhabdomyolysis in an adolescent athlete during preseason conditioning: a perfect storm. J Strength Cond Res 25(12): 3506-3513, 2011-The purpose of this brief review is to present a case of a healthy, male adolescent athlete (age = 16 years, body mass = 67.9 kg, height = 165.5 cm) who participated in a 3-day preseason wrestling camp which resulted in hospitalization for exertional rhabdomyolysis. As part of the preseason conditioning program directed by the coaches, the athlete completed 60 minutes of short, intense intervals of wall sits, squats, sit-ups, push-ups, lunges, and plyometric jumps. The following day, the athlete continued his vigorous training consisting of running drills. That night he noticed voiding dark brown urine the color of cola. The day after the camp ended, the athlete reported to his Athletic Trainers with the chief complaint of severe bilateral leg pain in his quadriceps. Two days after the initial assessment, he was admitted to the hospital where he was diagnosed with exertional rhabdomyolysis based on creatine kinase (CK) levels that peaked at 146,000 IU.L, elevated far beyond normal (normal range = 58-280 IU.L). The athlete was hospitalized for 6 days where he received intravenous normal saline for rehydration, and his CK levels were assessed daily. Athletic Trainers, personal trainers, physical education teachers, and coaches should be aware that exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals who participate in novel and intense exercise to which they are unaccustomed. Stressful ambient conditions may lead to dehydration and exacerbation of the condition, particularly when the individual is not accustomed to the exercise intensity. PMID- 22080316 TI - Determining the optimal whole-body vibration dose-response relationship for muscle performance. AB - Da Silva-Grigoletto, ME, de Hoyo, M, Sanudo, B, Corrales, L, and Garcia-Manso, JM. Determining the optimal whole-body vibration dose-response relationship for muscle performance. J Strength Cond Res 25(12): 3326-3333, 2011-The aim of this investigation was twofold: first, to determine the optimal duration of a single whole-body vibration (WBV) exposure (phase 1) and second to find out the ideal number of sets per intervention to maximize muscle performance (phase 2). All participants were young (age: 19.4 +/- 1.6 years), healthy, physically active men. In both studies, a 30-Hz frequency and a 4-mm peak-to-peak displacement were used. In phase 1, subjects (n = 30) underwent 3 sets of different durations (30, 60, and 90 seconds), whereas in phase 2, subjects (n = 27) underwent 3 interventions where the duration remained fixed at 60 seconds, and the number of sets performed (3, 6, or 9) was modified. The recovery time between sets was set at 2 minutes. In all interventions, each set consisted of 1 isometric repetition in a squat position with knees flexed at 100 degrees . Before and after each session, jump height (countermovement jump [CMJ] and squat jump [SJ]) and power output in half squat (90 degrees knee flexion) were assessed. In phase 1, an improvement in jump ability and power output was observed after the 30- and 60 second intervention (p < 0.01), whereas the 90 second intervention, participants just experienced a decrease in SJ and CMJ (p < 0.05). When comparing the different protocols, the greatest response was achieved using 60 seconds (p < 0.05), which was therefore considered as the optimal duration to be used in phase 2. In the second phase, improvements in jump ability and power output were found with 3 and 6 sets (p < 0.05), whereas with 9 sets, participants actually experienced a decrease in these variables. Intergroup comparison showed a greater effect for the program of 6 sets (p < 0.05). In conclusion, a WBV intervention consisting of six 60-second sets produces improved muscle performance measured by SJ, CMJ, and power output. PMID- 22080317 TI - Anthropometric and physiological characteristics of young soccer players according to their playing positions: relevance for competition success. AB - Lago-Penas, C, Casais, L, Dellal, A, Rey, E, and Dominguez, E. Anthropometric and physiological characteristics of young soccer players according to their playing positions: relevance for competition success. J Strength Cond Res 25(12): 3358 3367, 2011-The aim of this study was to establish the anthropometric and physiological profiles of young soccer players according to their playing position and to determine their relevance for competition success. Three hundred and twenty-one young male soccer players participated in the study. Players, age 15.63 (+/-1.82) years, range 12-19 years, were classified into the following groups: Goalkeepers (n = 35), Central Defenders (n = 53), External Defenders (n = 54), Central Midfielders (n = 61), External Midfielders (n = 46), and Forwards (n = 72). The anthropometric variables of participants (height, weight, body mass index, 6 skinfolds, 4 diameters, and 3 perimeters) were measured. Also, their somatotype and body composition (weights and percentages of fat, bone, and muscle) were calculated. Participants performed the 20-m progressive run test to estimate their relative VO(2)max, a sprint test (30 m flat), and 3 jump tests (squat jump, countermovement jump, and Abalakov test). External Midfielders were the leanest and shortest. In contrast, Central Defenders and Goalkeepers were found to be the tallest and heaviest players. They also had the largest fat skinfolds. In general, the results show that heavier and taller young soccer players performed better in vertical jumps and 30-m sprint, whereas leaner players performed better in the 20-m progressive run test. Players were classified into 2 groups according to the final ranking of their teams at the end of the season. Players from successful teams performed slightly better than players from unsuccessful teams in the physiological test, but these differences were not statistically significant. Moreover, players from successful teams were found to be leaner and more muscular than their unsuccessful counterparts. PMID- 22080318 TI - The effects of low fat chocolate milk on postexercise recovery in collegiate athletes. AB - Spaccarotella, KJ and Andzel, WD. The effects of low fat chocolate milk on postexercise recovery in collegiate athletes. J Strength Cond Res 25(12): 3456 3460, 2011-Drinking chocolate milk between exercise sessions may improve recovery. The purpose of this study was to examine the effects of low fat chocolate milk vs. a carbohydrate-electrolyte beverage (CE) on recovery between preseason practice sessions among 5 male and 8 female Division III soccer players. The study used a randomized crossover design: between morning and afternoon practices, athletes received either an amount of chocolate milk that provided 1 g carbohydrate per kilogram body weight or an equal volume of CE (mean volume of 615 +/- 101 ml). After their afternoon practice, they completed a shuttle run to fatigue. Data were analyzed using the Wilcoxon paired rank-sign test (for shuttle run time) and the paired samples t-test (for dietary intake). No significant differences in run time were reported for the group. For the men only, there was a trend of increased time to fatigue with chocolate milk compared with the CE (exact p = 0.03). Low fat chocolate milk may therefore be as good as a CE at promoting recovery between training sessions during preseason. PMID- 22080319 TI - Kinetic quantification of plyometric exercise intensity. AB - Ebben, WP, Fauth, ML, Garceau, LR, and Petushek, EJ. Kinetic quantification of plyometric exercise intensity. J Strength Cond Res 25(12): 3288-3298, 2011 Quantification of plyometric exercise intensity is necessary to understand the characteristics of these exercises and the proper progression of this mode of exercise. The purpose of this study was to assess the kinetic characteristics of a variety of plyometric exercises. This study also sought to assess gender differences in these variables. Twenty-six men and 23 women with previous experience in performing plyometric training served as subjects. The subjects performed a variety of plyometric exercises including line hops, 15.24-cm cone hops, squat jumps, tuck jumps, countermovement jumps (CMJs), loaded CMJs equal to 30% of 1 repetition maximum squat, depth jumps normalized to the subject's jump height (JH), and single leg jumps. All plyometric exercises were assessed with a force platform. Outcome variables associated with the takeoff, airborne, and landing phase of each plyometric exercise were evaluated. These variables included the peak vertical ground reaction force (GRF) during takeoff, the time to takeoff, flight time, JH, peak power, landing rate of force development, and peak vertical GRF during landing. A 2-way mixed analysis of variance with repeated measures for plyometric exercise type demonstrated main effects for exercise type and all outcome variables (p <= 0.05) and for the interaction between gender and peak vertical GRF during takeoff (p <= 0.05). Bonferroni adjusted pairwise comparisons identified a number of differences between the plyometric exercises for the outcome variables assessed (p <= 0.05). These findings can be used to guide the progression of plyometric training by incorporating exercises of increasing intensity over the course of a program. PMID- 22080320 TI - Biomechanical differences between incline and plane hopping. AB - Kannas, TM, Kellis, E, and Amiridis, IG. Biomechanical differences between incline and plane hopping. J Strength Cond Res 25(12): 3334-3341, 2011-The need for the generation of higher joint power output during performance of dynamic activities led us to investigate the force-length relationship of the plantar flexors during consecutive stretch-shortening cycles of hopping. The hypothesis of this study was that hopping (consecutive jumps with the knee as straight as possible) on an inclined (15 degrees ) surface might lead to a better jumping performance compared with hopping on a plane surface (0 degrees ). Twelve active men performed 3 sets of 10 consecutive hops on both an incline and plane surface. Ground reaction forces; ankle and knee joint kinematics; electromyographic (EMG) activity from the medial gastrocnemius (MG), soleus (Sol) and tibialis anterior (TA); and architectural data from the MG were recorded. The results showed that participants jumped significantly higher (p < 0.05) when hopping on an inclined surface (30.32 +/- 8.18 cm) compared with hopping on a plane surface (27.52 +/- 4.97 cm). No differences in temporal characteristics between the 2 types of jumps were observed. Incline hopping induced significantly greater ankle dorsiflexion and knee extension at takeoff compared with plane hopping (p < 0.05). The fascicle length of the MG was greater at initial contact with the ground during incline hopping (p < 0.05). Moreover, the EMG activities of Sol and TA during the propulsion phase were significantly higher during incline compared with that during plane hopping (p < 0.05). It does not seem unreasonable to suggest that, if the aim of hopping plyometrics is to improve plantar flexor explosivity, incline hopping might be a more effective exercise than hopping on a plane surface. PMID- 22080321 TI - Oxygen consumption and heart rate during repeated squatting exercises with or without whole-body vibration in the elderly. AB - Avelar, NCP, Simao, AP, Tossige-Gomes, R, Neves, CDC, Mezencio, B, Szmuchrowski, L, Coimbra, CC, and Lacerda, ACR. Oxygen consumption and heart rate during repeated squatting exercises with or without whole-body vibration in the elderly. J Strength Cond Res 25(12): 3495-3500, 2011-The aim of this study was to investigate whether vibration plus squatting would increase cardiovascular demand to the optimal exercise limits needed for the prescription of cardiovascular training. Oxygen consumption, measured breath by breath by a portable gas analysis system, and heart rate (HR), measured using an HR monitor, were evaluated in 18 elderly individuals, 15 women and 3 men with a mean age of 72 +/- 6 years. These variables were measured simultaneously and at the same time points in each subject during rest and randomly during the performance of squatting exercises (8 series of 40 seconds, with 40 seconds of rest between series of performing squats in 3-second cycles with 10-60 degrees of flexion, a total of 5 repetitions for 40 seconds) with or without vibration at a frequency of 40 Hz and amplitude of 4 mm, separated by at least 1 day. Associating whole-body vibration with squatting exercise resulted in an additional increase of around 20% in oxygen consumption and 7.5% in the HR recorded during exercise. However, during squatting exercise with vibration, the increase achieved in oxygen consumption was limited to around 2 metabolic equivalents, and mean HR represented around 56% of the predicted maximum HR for age. The results of this study show that, despite the fact that vibration increased oxygen consumption and HR during the performance of squatting exercise, the minimum standards of intensity for the prescription of physical exercise with the specific objective of improving cardiorespiratory fitness were not achieved. Therefore, a protocol such as that used in the study does not meet the threshold for cardiovascular training prescription. PMID- 22080322 TI - Fit women are not able to use the whole aerobic capacity during aerobic dance. AB - Edvardsen, E, Ingjer, F, and Bo, K. Fit women are not able to use the whole aerobic capacity during aerobic dance. J Strength Cond Res 25(12): 3479-3485, 2011-This study compared the aerobic capacity during maximal aerobic dance and treadmill running in fit women. Thirteen well-trained female aerobic dance instructors aged 30 +/- 8.17 years (mean +/- SD) exercised to exhaustion by running on a treadmill for measurement of maximal oxygen uptake (VO(2)max) and peak heart rate (HRpeak). Additionally, all subjects performed aerobic dancing until exhaustion after a choreographed videotaped routine trying to reach the same HRpeak as during maximal running. The p value for statistical significance between running and aerobic dance was set to <=0.05. The results (mean +/- SD) showed a lower VO(2)max in aerobic dance (52.2 +/- 4.02 ml.kg.min) compared with treadmill running (55.9 +/- 5.03 ml.kg.min) (p = 0.0003). Further, the mean +/- SD HRpeak was 182 +/- 9.15 b.min in aerobic dance and 192 +/- 9.62 b.min in treadmill running, giving no difference in oxygen pulse between the 2 exercise forms (p = 0.32). There was no difference in peak ventilation (aerobic dance: 108 +/- 10.81 L.min vs. running: 113 +/- 11.49 L.min). In conclusion, aerobic dance does not seem to be able to use the whole aerobic capacity as in running. For well endurance-trained women, this may result in a lower total workload at maximal intensities. Aerobic dance may therefore not be as suitable as running during maximal intensities in well-trained females. PMID- 22080323 TI - Factors of trainability and predictability associated with military physical fitness test success. AB - Cuddy, JS, Slivka, DR, Hailes, WS, and Ruby, BC. Factors of trainability and predictability associated with military physical fitness test success. J Strength Cond Res 25(12): 3486-3494, 2011-The purpose of this study was to determine the trainability of college-aged men using varied training programs and to assess factors associated with successfully passing a Special Operations Forces (SOF) physical fitness test (PFT). One hundred thirty-five male subjects were stratified into 3 training groups (run focused, calisthenic focused, or combined run and calisthenic) and were trained 3 times.per week for 12 weeks. Body composition and accelerometer activity patterns were measured pretraining and posttraining. The PFT performance (pull-ups, sit-ups, push-ups, and 1.5-mile run time) was measured weekly throughout the study period. The subjects exhibited reduced body fat (18.4 +/- 7.7 to 16.9 +/- 7.3), increased fat-free mass (66.1 +/ 8.2 to 67.4 +/- 7.9), reduced fat mass (15.8 +/- 9.2 to 14.6 +/- 8.9) from pretraining to posttraining, respectively (p < 0.05). All groups improved in each component of PFT performance with training (p < 0.05). There was a significant 20 +/- 35% increase in 6-day average daily activity for the run-focused training group from pretraining and posttraining. The key indicators of a candidate's potential to successfully reach SOF PFT standards (in 12 weeks) were determined to be as follows: enter the pipeline being able to run 2.4 km in <=10:41 minutes, have a body fat percentage of <=12.9%, and participate in a minimum of 30 min.d of vigorous physical activity. Training an individual's relative run or calisthenic deficiency did not prove to be a better training approach compared with a program that emphasizes training both running and calisthenic activities. PMID- 22080324 TI - The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained men. AB - Trepanowski, JF, Farney, TM, McCarthy, CG, Schilling, BK, Craig, SA, and Bloomer, RJ. The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation, and associated biochemical parameters in resistance trained men. J Strength Cond Res 25(12): 3461-3471, 2011-We examined the effects of chronic betaine supplementation on exercise performance and associated parameters in resistance trained men. Men were randomly assigned in a double-blind manner using a crossover design to consume betaine (2.5 g of betaine mixed in 500 ml of Gatorade(r)) or a placebo (500 ml of Gatorade(r)) for 14 days, with a 21-day washout period. Before and after each treatment period, tests of lower- and upper-body muscular power and isometric force were conducted, including a test of upper-body muscular endurance (10 sets of bench press exercise to failure). Muscle tissue oxygen saturation (StO2) during the bench press protocol was measured via near infrared spectroscopy. Blood samples were collected before and after the exercise test protocol for analysis of lactate, nitrate/nitrite (NOx), and malondialdehyde (MDA). When analyzed using a repeated measures analysis of variance, no significant differences were noted between conditions for exercise performance variables (p > 0.05). However, an increase in total repetitions (p = 0.01) and total volume load (p = 0.02) in the 10-set bench press protocol was noted with betaine supplementation (paired t-tests), with values increasing approximately 6.5% from preintervention to postintervention. Although not of statistical significance (p = 0.14), postexercise blood lactate increased to a lesser extent with betaine supplementation (210%) compared with placebo administration (270%). NOx was lower postintervention as compared with preintervention (p = 0.06), and MDA was relatively unchanged. The decrease in StO2 during the bench press protocol was greater with betaine vs. placebo (p = 0.01), possibly suggesting enhanced muscle oxygen consumption. These findings indicate that betaine supplementation results in a moderate increase in total repetitions and volume load in the bench press exercise, without favorably impacting other performance measures. PMID- 22080325 TI - Kinetic comparisons during variations of the power clean. AB - Comfort, P, Allen, M, and Graham-Smith, P. Kinetic comparisons during variations of the power clean. J Strength Cond Res 25(12): 3269-3273, 2011-The aim of this investigation was to determine the differences in peak power, peak vertical ground reaction forces, and rate of force development (RFD) during variations of the power clean. Elite rugby league players (n = 16; age 22 +/- 1.58 years; height 182.25 +/- 2.81 cm; body mass 98.65 +/- 7.52 kg) performed 1 set of 3 repetitions of the power clean, hang power clean, midthigh power clean, or midthigh clean pull, using 60% of 1 repetition maximum power clean, in a randomized order, while standing on a force platform. One-way analysis of variance with Bonferroni post hoc analysis revealed a significantly (p < 0.001) greater peak power output during the midthigh power clean (3,565.7 +/- 410.6 W) and the midthigh clean pull (3,686.8 +/- 386.5 W) compared with both the power clean (2,591.2 +/- 645.5 W) and the hang power clean (3,183.6 +/- 309.1 W), along with a significantly (p < 0.001) greater peak Fz during the midthigh power clean (2,813.8 +/- 200.5 N) and the midthigh clean pull (2,901.3 +/- 226.1 N) compared with both the power clean (2,264.1 +/- 199.6 N) and the hang power clean (2,479.3 +/- 267.6 N). The midthigh power clean (15,049.8 +/- 4,415.7 N.s) and the midthigh clean pull (15,623.6 +/- 3,114.4 N.s) also demonstrated significantly (p < 0.001) greater instantaneous RFD when compared with both the power clean (8,657.9 +/- 2,746.6 N.s) and the hang power clean (10,314.4 +/- 4,238.2 N.s). From the findings of this study, when training to maximize power, Fz, and RFD, the midthigh power clean and midthigh clean pull appear to be the most advantageous variations of the power clean to perform. PMID- 22080326 TI - Is it time to consider a new performance classification for high-level male marathon runners? AB - La Torre, A, Vernillo, G, Agnello, L, Berardelli, C, and Rampinini, E. Is it time to consider a new performance classification for high-level male marathon runners? J Strength Cond Res 25(12): 3242-3247, 2011-Studies have attempted to describe human running performances by the analysis of world-record times. However, to date, no study has analyzed the evolution of high-level marathon performances over time. Thus, the purpose of this study was to analyze these performances across the past 42 years with the aim of delineating a time-based classification. To identify the nature of the phenomenon represented by the sequence of observations, we examined the data collected (i.e., 8,400 times from 1969 to 2010) as a time series. The leading time (LT) and the mean 200 times (T200) per year underwent a nonlinear but significant decrement (r = -0.92, p < 0.001 and r = -0.98, p < 0.001, respectively). In fact, from 1969 to 2010, the mean time differences were 3 minutes 20 seconds +/- 1 minute 59 seconds and 7 minutes 1 second +/- 2 minutes 48 seconds, corresponding to an improvement of 5 and 10 seconds per year for LT and T200, respectively. Furthermore, trend analysis suggested a disruption in marathon time improvements, indicating the presence of 3 points in the time series in which the performance significantly improved with respect to that of the previous years, corresponding to the years 1983-1984 (p < 0.001), 1997-1998 (p < 0.003), and 2003 (p < 0.001). In conclusion, despite the trend in high-level marathon performances being better explained by a nonlinear tendency, significant improvements in the ability of the high-level marathon runners to complete the distance were observed. These improvements are likely to be related to sociological, environmental, physiological, and training-method factors. Researchers and coaches should take into account these enhancements by using the time classification proposed in this study to better reflect the marathon performance profile of their athletes. PMID- 22080327 TI - Dissipation kinetics of trifloxystrobin and tebuconazole on chili and soil. AB - Dissipation of trifloxystrobin and tebuconazole were studied following two applications of a combination formulation of Nativo 75 WG (trifloxystrobin 25% + tebuconazole 50%) @ 250 and 500 g ha(-1) at 10 days interval. Samples of chili were collected at 0, 1, 3, 5, 7, 10 and 15 days after the last application. Red chili and soil samples were collected after 20 days of last application. Half life period for trifloxystrobin were found to be 1.81 and 1.58 days and for tebuconazole these values were observed to be 1.37 and 1.41 days, respectively, at single and double the application rates. Trifloxystrobin residues dissipated below its limit of quantification (LOQ) of 0.01 mg kg(-1) after 5 and 7 days, respectively, at single and double the application dosages whereas tebuconazole residues took 7 and 10 days, respectively. Red chili & soil samples collected after 20 days did not reveal the presence of trifloxystrobin and tebuconazole at their determination limit of 0.01 mg kg(-1). PMID- 22080328 TI - Distribution of aliphatic and aromatic hydrocarbons in red mullet (Mullus barbatus) and annular sea bream (Diplodus annularis) from the Izmir Bay (eastern Aegean). AB - Polycyclic aromatic and aliphatic hydrocarbons were analyzed in red mullet and annular sea bream from the Izmir Bay. These fishes were selected because of their multitude, wide distribution and common use in the Turkish diet; they were sampled and analyzed in 2000-2001 and 2004-2005 periods at five locations by trawling. Red mullet showed higher PAHs and aliphatics than annular sea bream. PAH levels for red mullet and annular sea bream ranged from 202 to 556 and 78.7 to 415; aliphatics ranged from 834 to 2,420 and 436 to 1,724 ng/g dw, respectively. Molecular ratios showed pyrolitic inputs for PAHs, biogenic and anthropogenic inputs for aliphatics. The carcinogenic PAH, benzo(a)pyrene, was detected in most fish samples in levels ranged between 22.2 and 64.1 ng/g dw. The average PAH contamination level was within the "moderate" category in fish from Izmir Bay. Results indicate the needing of a systematic monitoring program in order to provide accurately assessment and management of risks for the regional population. PMID- 22080329 TI - Catalytic conversion of methane to methanol over Cu-mordenite. AB - Methane can be converted to methanol over copper-exchanged mordenite at 200 degrees C. Methanol could be recovered at the end of the reactor. This multi-step reaction opens the possibility for methane to methanol conversion in a closed catalytic cyclic reaction system. PMID- 22080330 TI - Substrate utilization by recombinant Yarrowia lipolytica growing on sucrose. AB - We report the study of the dynamics of substrate utilization by the genetic modified strain Yarrowia lipolytica H222-S4(p67ICL1) T5. In contrast to its wild type equivalent, this recombinant strain is able to excrete the sucrose cleaving enzyme invertase. Both the sucrose degradation rate and the glucose and fructose consumption rate have been investigated. In all experiments, satisfied amounts of invertase were produced so that all sucrose was cleaved into its monomers. While glucose and fructose as sole carbon sources were consumed with the same uptake rate, a clear preference for glucose uptake was detected in cultivations with sucrose as sole carbon source or mixed substrates when compared with fructose. Nevertheless, no real diauxie could be observed because of partly simultaneous consumption of both monosaccharides. Fructose being present in the cultivation medium at the beginning of the fermentation led to the retardation of glucose uptake. This effect was observed for various fructose starting concentrations in the range of 5-85 g/l. PMID- 22080331 TI - One-step engineering of silver nanoclusters-aptamer assemblies as luminescent labels to target tumor cells. AB - We reported one-step engineering of intrinsically fluorescent silver nanoclusters aptamer assemblies that would allow the development of facile and specific luminescent labels for target tumor cell recognition and analysis. PMID- 22080332 TI - Right ventricular injury in ST-elevation myocardial infarction: risk stratification by visualization of wall motion, edema, and delayed-enhancement cardiac magnetic resonance. AB - BACKGROUND: Patients with right ventricular injury (RVI) complicating ST elevation myocardial infarction (STEMI) have impaired prognosis, but it is unclear which patients are at risk of developing RVI. Cardiac magnetic resonance can identify these patients and might add important information on risk stratification, prognosis, and treatment. Aims were to determine the predictors and the prognostic significance of RVI assessed by wall motion abnormalities, edema, myocardial salvage index, and delayed enhancement in acute reperfused STEMI. METHODS AND RESULTS: We studied 450 patients 1-4 days after primary angioplasty in STEMI. T2-weighted and delayed-enhancement cardiac magnetic resonance was used for visualizing edema and scar to calculate myocardial salvage index. Cine-imaging was performed to assess wall motion abnormalities, which, in combination with edema, were considered diagnostic for RVI. Patients with RVI were compared with matched patients with isolated left ventricular infarction. The primary end point was the occurrence of a major adverse cardiac event: a composite of death, reinfarction, and congestive heart failure after a median follow-up period of 20.9 months. RVI was present in 69 patients, and 41 of 69 showed myocardial necrosis. In a multivariable stepwise forward logistic regression analysis, a high RV myocardial mass (odds ratio, 2.06; 95% confidence interval, 1.18-3.58; P=0.012) and a low Thrombolysis In Myocardial Infarction flow before angioplasty (odds ratio, 0.50; 95% confidence interval, 0.32-0.76; P=0.011) were associated with RVI. Cox regression analysis revealed RVI as the most statistically significant predictor of time to major adverse cardiac events (hazard-ratio, 3.36; 95% confidence interval, 1.99-5.66; P<0.001). CONCLUSIONS: RVI detected by cardiac magnetic resonance is a strong and independent predictor of clinical outcome after acute reperfused STEMI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01359306. PMID- 22080333 TI - Low valent and hydride complexes of NHC coordinated gallium and indium. AB - The reactions of the N-heterocyclic carbene 1,3-dimesitylimidazol-2-ylidene (IMes) with Ga[GaCl(4)], "GaI", InCl(2) and GaBr(3) have been examined. All reactions using a low valent gallium or indium starting material led to species of the form [{MX(2)(IMes)}(2)], where M = Ga, X = Cl (1), I (2); M = In, X = Cl (3), with disproportionation and loss of gallium metal in the case of 2. Reaction of IMes with gallium tribromide yields the air and moisture stable complex [GaBr(3)(IMes)] (4), which has been used as a precursor to the mixed bromohydrides [GaBrH(2)(IMes)] (5) and [GaBr(2)H(IMes)] (6) by (i) ligand redistribution with [GaH(3)(IMes)], (ii) hydride-bromide exchange with triethylsilane, and (iii) alkylation with (n)butyllithium followed by beta hydride elimination (6 only). Attempts to prepare 1, or monovalent analogues such as [{GaCl(IMes)}(n)], by thermally induced reductive elimination of dihydrogen from the chlorohydride congeners of 5 and 6 resulted in isolation of the known compounds [IMesCl][Cl] (IMesCl = 1,3-dimesityl-2-chloroimidazolium), and/or 1,3 dimesityl-2-dihydroimidazole, and gallium metal. Preliminary photochemical NMR spectroscopy and catalytic studies of 5 and 6 aimed at reductive dehydrogenation under milder conditions are reported. Compounds 1 and 4 have been characterised by single crystal X-ray structure determination. PMID- 22080335 TI - New mode of treatment for lattice corneal dystrophy type I: corneal epithelial debridement and fibronectin eye drops. AB - PURPOSE: The R124C mutation of the TGFBI gene gives rise to lattice corneal dystrophy type I, which is characterized by irregularity, turbulence, and opacity of the corneal epithelium. We investigated the efficacy of corneal epithelial debridement followed by application of autologous fibronectin eye drops in the treatment of patients with this mutation. METHODS: Four patients (6 eyes; age range 25-57 years) treated between April 2006 and March 2008 were enrolled in the study. All patients had impaired visual acuity and recurrent corneal erosion. Corneal epithelial debridement was performed with a spatula at the pupillary zone, after which eye drops containing fibronectin purified from autologous serum were administered four times daily for 2 weeks to promote epithelial migration. Topical levofloxacin and betamethasone were also applied four times daily for 1 month. RESULTS: All corneas achieved resurfacing within a few days of debridement. The best corrected visual acuity of all eyes improved from an average logMAR of 0.80 (range 1.40 logMAR-0.52 logMAR) before treatment to a logMAR of 0.10 (range 0.30 logMAR-0.046 logMAR) by 2-4 months after debridement. CONCLUSION: Despite the limitation of this study setting, corneal epithelial debridement followed by administration of fibronectin eye drops seems to be effective in improving visual acuity in cases of lattice corneal dystrophy type I caused by the R124C mutation of the TGFBI gene. This treatment may be one option for temporarily improving visual acuity in lattice corneal dystrophy type I and thus may delay the requirement for phototherapeutic keratoplasty or keratoplasty. PMID- 22080336 TI - Beyond ESWL: new concepts for definitive stone removal. PMID- 22080334 TI - Integrating etiological models of social anxiety and depression in youth: evidence for a cumulative interpersonal risk model. AB - Models of social anxiety and depression in youth have been developed separately, and they contain similar etiological influences. Given the high comorbidity of social anxiety and depression, we examine whether the posited etiological constructs are a correlate of, or a risk factor for, social anxiety and/or depression at the symptom level and the diagnostic level. We find core risk factors of temperament, genetics, and parent psychopathology (i.e., depression and anxiety) are neither necessary nor sufficient for the development of social anxiety and/or depression. Instead, aspects of children's relationships with parents and/or peers either mediates (i.e., explains) or moderates (i.e., interacts with) these core risks being related to social anxiety and/or depression. We then examine various parent- and peer-related constructs contained in the separate models of social anxiety and depression (i.e., parent-child attachment, parenting, social skill deficits, peer acceptance and rejection, peer victimization, friendships, and loneliness). Throughout our review, we report evidence for a Cumulative Interpersonal Risk model that incorporates both core risk factors and specific interpersonal risk factors. Most studies fail to consider comorbidity, thus little is known about the specificity of these various constructs to depression and/or social anxiety. However, we identify shared, differential, and cumulative risks, correlates, consequences, and protective factors. We then put forth demonstrated pathways for the development of depression, social anxiety, and their comorbidity. Implications for understanding comorbidity are highlighted throughout, as are theoretical and research directions for developing and refining models of social anxiety, depression, and their comorbidity. Prevention and treatment implications are also noted. PMID- 22080338 TI - Nurse staffing and inpatient mortality: is the question outcomes or nursing value? PMID- 22080337 TI - Identifying specific chemotherapeutic agents in Medicare data: a validation study. AB - BACKGROUND: Large health care databases are increasingly used to examine the dissemination and benefits and harms of chemotherapy treatment in routine practice, particularly among patients excluded from trials (eg, the elderly). Misclassification of chemotherapy could bias estimates of frequency and association, warranting an updated assessment. METHODS: We evaluated the validity of Medicare claims to identify receipt of chemotherapy and specific agents delivered to elderly stage II/III colorectal (CRC), in situ/early-stage breast, non-small-cell lung, and ovarian cancer patients using the National Cancer Institute's Patterns of Care studies (POC) as the gold standard. The POC collected data on chemotherapy treatment by reabstracting hospital records, contacting physicians, and reviewing medical records. Patients' POC data were linked and compared with their Medicare claims for 2 to 12 months postdiagnosis. kappa, sensitivity, specificity, positive and negative predictive values and 95% confidence intervals were calculated for the receipt of any chemotherapy and specific agents. RESULTS: Sensitivity and specificity of Medicare claims to identify any chemotherapy were high across all cancer sites. We found substantial variation in validity across agents, by site and administration modality. Capecitabine, an oral CRC treatment, was identified in claims with high specificity (98%) but low sensitivity (47%), whereas oxaliplatin, an intravenously administered CRC agent had higher sensitivity (75%) and similar specificity (97%). CONCLUSIONS: Receipt of chemotherapy and specific intravenous agents can be identified using Medicare claims, showing improvement from prior reports; yet, variation exists. Future studies should assess newly approved agents and the impact of coverage decisions for these agents under the Medicare Part D program. PMID- 22080339 TI - Nanotube-based hierarchical titanate microspheres: an improved anode structure for Li-ion batteries. AB - We report a facile hydrothermal route for the large scale preparation of H titanate with a novel urchin-like nano/micro structure. Due to the features of its microsized spherical structure assembled by nanosized quasi-1D tubular components, this novel nano/micro structure shows to be a good potential anode material for Li-ion batteries. PMID- 22080340 TI - Enhanced performance and mechanism study of microbial electrolysis cells using Fe nanoparticle-decorated anodes. AB - Anode properties are critical for the performance of microbial electrolysis cells (MECs). In the present study, Fe nanoparticle-modified graphite disks were used as anodes to investigate the effects of nanoparticles on the performance of Shewanella oneidensis MR-1 in MECs. Results demonstrated that the average current densities produced with Fe nanoparticle-decorated anodes up to 5.89-fold higher than plain graphite anodes. Whole genome microarray analysis of the gene expression showed that genes encoding biofilm formation were significantly up regulated as a response to nanoparticle-decorated anodes. Increased expression of genes related to nanowires, flavins, and c-type cytochromes indicates that enhanced mechanisms of electron transfer to the anode may also have contributed to the observed increases in current density. The majority of the remaining differentially expressed genes associated with electron transport and anaerobic metabolism demonstrate a systemic response to increased power loads. PMID- 22080341 TI - Performance linked to residence time distribution by a novel wool-based bioreactor for tertiary sewage treatment. AB - Laboratory-scale experiments were carried out using up-flow 7 L Submerged Aerated Filter reactors packed with wool fibre or commercial plastic pall rings, Kaldnes, (70% by volume) support media for the tertiary treatment of sewage. The performance of the wool bioreactor was more consistent than that with Kaldnes medium, for both TOC removal (93%) and SS removal (90%). Both plastic and wool packed bioreactors achieved complete nitrification at the load of about 0.4 kgCOD/m(3)/day. The sludge yield of the wool bioreactor was almost half that of the bioreactor with Kaldnes suggesting that wool could retain residual organics and particulates. The wool however was degraded and it was concluded that wool would have to be considered as additional sacrificial adsorption capacity rather than an alternative medium. The performance was linked to the residence time distribution studies and these changes in the wool structure. Biomass growth increased the retention of the tracer in the wool reactor by, it was suggested, exposing a greater surface area. Results from the plastic media on the other hand showed increased mixing possibly by increasing the mobility of the plastic. Aeration increased the mixing in both reactors, and patterns were in all cases predominantly well-mixed. PMID- 22080342 TI - Simple and efficient expression of Agaricus meleagris pyranose dehydrogenase in Pichia pastoris. AB - Pyranose dehydrogenase (PDH) is a fungal flavin-dependent sugar oxidoreductase that is highly interesting for applications in organic synthesis or electrochemistry. The low expression levels of the filamentous fungus Agaricus meleagris as well as the demand for engineered PDH make heterologous expression necessary. Recently, Aspergillus species were described to efficiently secrete recombinant PDH. Here, we evaluate recombinant protein production with expression hosts more suitable for genetic engineering. Expression in Escherichia coli resulted in no soluble or active PDH. Heterologous expression in the methylotrophic yeast Pichia pastoris was investigated using two different signal sequences as well as a codon-optimized sequence. A 96-well plate activity screening for transformants of all constructs was established and the best expressing clone was used for large-scale production in 50-L scale, which gave a volumetric yield of 223 mg L(-1) PDH or 1,330 U L(-1) d(-1) in space-time yield. Purification yielded 13.4 g of pure enzyme representing 95.8% of the initial activity. The hyperglycosylated recombinant enzyme had a 20% lower specific activity than the native enzyme; however, the kinetic properties were essentially identical. This study demonstrates the successful expression of PDH in the eukaryotic host organism P. pastoris paving the way for protein engineering. Additionally, the feasibility of large-scale production of the enzyme with this expression system together with a simplified purification scheme for easy high yield purification is shown. PMID- 22080344 TI - A hemolytic peptide from the mycophilic fungus Sepedonium chrysospermum (Bull.) Fr. AB - The hemolytic activity of an extract of the mycoparasite Sepedonium chrysospermum (teleomorph Hypomyces chrysospermus) was detected and characterized. Extraction of the fungal biomass by methanol yielded a fraction in which the hemolytic activity against human red blood cells corresponded to a peptide with a molecular mass of 7,653.72 Da and an isoelectric point of approximately 5.8. The peptide was temperature resistant, and the hemolysis was only partially inhibited, even after a 30-min pre-incubation at 100 degrees C. Its hemolytic activity was unaffected by treatment with proteolytic enzymes such as trypsin. Among the divalent cations assayed, Hg(2+) was the strongest inhibitor of hemolysis. The reducing agent, dithiothreitol, and the membrane lipid, cholesterol, demonstrated concentration-dependent inhibitory activities. Finally, hemolytic activity triggered by the peptide was analyzed by scanning electron microscopy, and a pore forming activity was detected. PMID- 22080343 TI - A homologous production system for Trichoderma reesei secreted proteins in a cellulase-free background. AB - Recent demands for the production of biofuels from lignocellulose led to an increased interest in engineered cellulases from Trichoderma reesei or other fungal sources. While the methods to generate such mutant cellulases on DNA level are straightforward, there is often a bottleneck in their production since a correct posttranslational processing of these enzymes is needed to obtain highly active enzymes. Their production and subsequent enzymatic analysis in the homologous host T. reesei is, however, often disturbed by the concomitant production of other endogenous cellulases. As a useful alternative, we tested the production of cellulases in T. reesei in a genetic background where cellulase formation has been impaired by deletion of the major cellulase transcriptional activator gene xyr1. Three cellulase genes (cel7a, cel7b, and cel12a) were expressed under the promoter regions of the two highly expressed genes tef1 (encoding translation elongation factor 1-alpha) or cdna1 (encoding the hypothetical protein Trire2:110879). When cultivated on D: -glucose as carbon source, the Deltaxyr1 strain secreted all three cellulases into the medium. Related to the introduced gene copy number, the cdna1 promoter appeared to be superior to the tef1 promoter. No signs of proteolysis were detected, and the individual cellulases could be assayed over a background essentially free of other cellulases. Hence this system can be used as a vehicle for rapid and high throughput testing of cellulase muteins in a homologous background. PMID- 22080345 TI - A family GH51 alpha-L-arabinofuranosidase from Pleurotus ostreatus: identification, recombinant expression and characterization. AB - An alpha-L-arabinofuranosidase produced by Pleurotus ostreatus (PoAbf) during solid state fermentation on tomato pomace was identified and the corresponding gene and cDNA were cloned and sequenced. Molecular analysis showed that the poabf gene carries 26 exons interrupted by 25 introns and has an open reading frame encoding a protein of 646 amino acid residues, including a signal peptide of 20 amino acid residues. The amino acid sequence similar to the other alpha-L arabinofuranosidases indicated that the enzyme encoded by poabf can be classified as a family 51 glycoside hydrolase. Heterologous recombinant expression of PoAbf was carried out in the yeasts Pichia pastoris and Kluyveromyces lactis achieving the highest production level of the secreted enzyme (180 mg L(-1)) in the former host. rPoAbf produced in P. pastoris was purified and characterized. It is a glycosylated monomer with a molecular weight of 81,500 Da in denaturing conditions. Mass spectral analyses led to the localization of a single O glycosylation site at the level of Ser160. The enzyme is highly specific for alpha-L-arabinofuranosyl linkages and when assayed with p-nitrophenyl alpha-L arabinofuranoside it follows Michaelis-Menten kinetics with a K (M) of 0.64 mM and a k (cat) of 3,010 min(-1). The optimum pH is 5 and the optimal temperature 40 degrees C. It is worth noting that the enzyme shows a very high stability in a broad range of pH. The more durable activity showed by rPoAbf in comparison to the other alpha-L-arabinofuranosidases enhances its potential for biotechnological applications and increases interest in elucidating the molecular bases of its peculiar properties. PMID- 22080346 TI - Updates on naringinase: structural and biotechnological aspects. AB - Naringinases has attracted a great deal of attention in recent years due to its hydrolytic activities which include the production of rhamnose, and prunin and debittering of citrus fruit juices. While this enzyme is widely distributed in fungi, its production from bacterial sources is less commonly known. Fungal naringinase are very important as they are used industrially in large amounts and have been extensively studied during the past decade. In this article, production of bacterial naringinase and potential biotechnological applications are discussed. Bacterial rhamnosidases are exotype enzymes that hydrolyse terminal non-reducing alpha-L-rhamnosyl groups from alpha-L-rhamnose containing polysaccharides and glycosides. Structurally, they are classified into family 78 of glycoside hydrolases and characterized by the presence of Asp567 and Glu841 in their active site. Optimization of fermentation conditions and enzyme engineering will allow the development of improved rhamnosidases for advancing suggested industrial applications. PMID- 22080347 TI - Isolation of a strong promoter fragment from endophytic Enterobacter cloacae and verification of its promoter activity when its host strain colonizes banana plants. AB - To engineer endophytic Enterobacter cloacae as a biocontrol agent against banana fusarium wilt, a promoter-probe plasmid pUCK was constructed to identify a strong promoter to express disease resistance genes. Using a kanamycin resistance gene for selection, 10 fragments with strong promoter activity were identified from the genome of the E. cloacae KKWB-10 strain. The regions of these 10 fragments that were the primary contributors to the promoter function were identified, and their promoter activities were further evaluated using green fluorescent protein (GFP) as a reporter gene. Fragment 132a" drove the highest level of GFP activity when the bacteria bearing the fragments were cultured in Luria-Bertani and banana stem extract media. The GFP-expressing strain harboring fragment 132a" (K-pUCK7 132a"-GT) was then inoculated into banana plantlets (about 1 * 10(7) CFU per plant) to verify the activity of fragment 132a" in planta. Ten days after inoculation, tissue sections of these banana plantlets were observed by laser confocal scanning microscope. Green fluorescence was observed in the tissues of banana plantlets inoculated with K-pUCK7-132a"-GT but not in uninoculated controls. These results suggest that fragment 132a" possesses strong promoter activity when its host strain colonizes the banana plants and can be used to engineer endophytic E. cloacae KKWB-10 for biocontrol. PMID- 22080348 TI - Physiological conditions conducive to high cell density and high cyanophycin content in Ralstonia eutropha strain H16 possessing a KDPG aldolase gene dependent addiction system. AB - The recombinant strain of Ralstonia eutropha H16-PHB(-)4-?eda (pBBR1MCS-2::cphA (6308)/eda (H16)) presenting a 2-keto-3-desoxy-phosphogluconate (KDPG) aldolase (eda) gene-dependent catabolic addiction system for plasmid maintenance when using gluconate or fructose as sole carbon source was used in this study. The effects of the initial pH, the nitrogen-to-carbon ratio, the inorganic components of medium, the oxygen supply, and the different carbon and nitrogen sources on the cell dry matter (CDM) and the cyanophycin granule polypeptide (CGP) content of the cells were studied in a mineral salts medium (MSM) without any additional amino acids or CGP precursor substrates. The experiments were designed to systematically find out the optimal conditions for growth of cells to high densities and for high CGP contents of the cells. Maximum contents of water insoluble CGP and water-soluble CGP, contributing to 47.5% and 5.8% (w/w) of CDM, respectively, were obtained at the 30-L scale cultivation when cells were cultivated in MSM medium containing sufficient supplements of fructose, NH(3), K(2)SO(4), MgSO(4)[Symbol: see text]7H(2)O, Fe(SH)NH(4)-citrate, CaCl(2)[Symbol: see text]2H(2)O, and trace elements (SL6). The molecular masses of water insoluble and water-soluble CGP ranged from 25 to 31 kDa and from 15 to 21 kDa, respectively. High cell densities of up to 82.8 g CDM/L containing up to 37.8% (w/w) water-insoluble CGP at the 30-L scale cultivation were also obtained. This is by far the best combination of high cell density and high cellular CGP contents ever reported, and it showed that efficient production of CGP at the industrial scale in white biotechnology could be achieved. PMID- 22080349 TI - Delta screw versus RetroScrew tibial fixation for ACL reconstruction. AB - PURPOSE: The purpose of this study is to determine whether the RetroScrew tibial fixation system offers a biomechanical advantage over the Delta screw for anterior cruciate ligament (ACL) reconstruction in cadaveric tibias with low bone mineral density (BMD). METHODS: Ten matched pairs of osteoporotic cadaveric tibiae underwent simulated ACL reconstruction using quadrupled hamstring grafts with one of the two tibial fixation constructs. Group 1 was fixed with the Delta screw (DS; 35-mm antegrade biointerference screw), and group 2 was fixed with the RetroScrew system (RSS; 20-mm retrograde and 17-mm antegrade biointerference screws). Each construct was cyclically loaded (50-200 N, 1 Hz, 500 cycles) and subsequently loaded to failure (20 mm/s). RESULTS: All specimens were osteoporotic without significant segmental (proximal, middle, and distal) BMD differences between groups by quantitative computed tomography (P = n.s.). A trend was noted for more construct failures due to graft slippage in the DS group (n = 3) over the RSS group (n = 1). There were no significant differences in cyclic displacement (P = n.s.), maximum cyclic stiffness (P = n.s.), maximum load at failure (P = n.s.), or pullout stiffness (P = n.s.) between groups. CONCLUSIONS: In an osteoporotic cadaveric model, there was no significant biomechanical advantage of the RetroScrew system versus the Delta screw for tibial fixation in soft tissue graft ACL reconstruction. However, a trend toward lower graft fixation failure to cyclic loading was noted with the RetroScrew system. PMID- 22080350 TI - Arthroscopic treatment of localized pigmented villonodular synovitis of the knee. AB - PURPOSE: The purpose of this study was to review the outcome of the arthroscopic treatment of localized pigmented villonodular synovitis of the knee and to determine the recurrence rate with clinical and magnetic resonance imaging evaluation at midterm follow-up. METHODS: Thirty consecutive patients diagnosed with localized pigmented villonodular synovitis of the knee were treated arthroscopically between 1990 and 2008. Clinical assessment was made with the use of Lysholm Knee Scale, and radiologic assessment was done by plain radiographs and magnetic resonance imaging of the knee. Recurrence rate of the disease was also estimated. RESULTS: The average follow-up was 75 months (range 12-144). The median age of the patients was 46 years (range 23-71). Symptoms were discomfort of the knee (100%), swelling (90%), locking (50%), pain (10%) and palpable mass (15%). A history of knee trauma was present in 10% of the patients. The nodules were localized in the gutters (45%), suprapatellar pouch (26%), patellar fat pad (13%), posterior compartment of the knee (13%) and in the femoral notch (9%). The median Lysholm Knee Score was 56.5 (range 53-60) and 85.5 (83-88) preoperatively and at final follow-up, respectively. No postoperative complications occurred. CONCLUSIONS: Arthroscopy is a safe and effective procedure for the treatment of localized pigmented villonodular synovitis of the knee. Magnetic resonance imaging is essential to diagnose this pathologic condition and to define accurately its localization and treatment strategy. PMID- 22080351 TI - Predisposing risk factors for non-contact ACL injuries in military subjects. AB - PURPOSE: The goal of this study was to document the incidence of anterior cruciate ligament (ACL) tears and possible risk factors for these injuries in a large population of young, athletic subjects. METHODS: The authors retrospectively reviewed the US Naval Academy's database of midshipmen admitted in 1999 and 2000 (n = 2,345) and prospectively followed until graduation 4 years later or disenrollment. Excluded were 658 who had a history of preadmission ACL injury or surgery, those without initial radiographs or documented baseline height and weight, or those who had documented contact ACL injuries. Therefore, 1,687 subjects comprised the study group. Standard radiographic measurements, including condylar width, notch width, and femoral notch width index (notch width divided by condyle width), were obtained for all subjects. Statistical analyses were used to determine differences between injured and uninjured subjects. RESULTS: The overall incidence of non-contact ACL injury was 2.9% (37 men, 12 women). The average BMI was 25.6 and 24.4 kg/m(2) for the injured and uninjured groups, respectively (P < 0.05). Although femoral notch width alone was not associated with non-contact ACL injuries, subjects with higher than average BMI in combination with narrow notch width were at significant risk for ACL injury (P = 0.021). CONCLUSIONS: Elevated BMI combined with narrow notch width may predispose young athletes to non-contact ACL injury. LEVEL OF EVIDENCE: Retrospective comparative study, Level III. PMID- 22080352 TI - Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route. AB - In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL(-1), but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration. PMID- 22080353 TI - Oxidation and coupling of beta-diketiminate ligand in lanthanide complexes: novel eight-nuclear lanthanide clusters with MU-, MU3-Cl, and MU4-O bridge. AB - Two novel eight-nuclear lanthanide oxide and chloride clusters Ln(8)(MU-eta(2) L(4))(2)(MU(3)-Cl)(4)(MU-Cl)(10)(MU(4)-O)(3)(THF)(8) (Ln = Er(3), Dy(4); L(4) = [OC{(Me)CN-2,6-(i)PrC(6)H(3)}(2)](2-)) have been synthesized by the reaction of beta-diketiminate rare-earth metal chlorides with oxygen, providing a new oxidation and coupling reaction of the beta-diketiminate ligand. PMID- 22080355 TI - Bilateral lesions of the medial frontal cortex disrupt recognition of social hierarchy during antiphonal communication in naked mole-rats (Heterocephalus glaber). AB - Generation of the motor patterns of emotional sounds in mammals occurs in the periaqueductal gray matter of the midbrain and is not directly controlled by the cortex. The medial frontal cortex indirectly controls vocalizations, based on the recognition of social context. We examined whether the medial frontal cortex was responsible for antiphonal vocalization, or turn-taking, in naked mole-rats. In normal turn-taking, naked mole-rats vocalize more frequently to dominant individuals than to subordinate ones. Bilateral lesions of the medial frontal cortex disrupted differentiation of call rates to the stimulus animals, which had varied social relationships to the subject. However, medial frontal cortex lesions did not affect either the acoustic properties of the vocalizations or the timing of the vocal exchanges. This suggests that the medial frontal cortex may be involved in social cognition or decision making during turn-taking, while other regions of the brain regulate when animals vocalize and the vocalizations themselves. PMID- 22080356 TI - Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease. AB - Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, is a rare autosomal recessive disorder characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor complex expressed on osteoclasts, dendritic cells, macrophages, monocytes, and microglia. At present, the precise molecular mechanisms underlying development of leukoencephalopathy and bone cysts in NHD remain largely unknown. We established THP-1 human monocyte clones that stably express small interfering RNA targeting DAP12 for serving as a cellular model of NHD. Genome-wide transcriptome analysis identified a set of 22 genes consistently downregulated in DAP12 knockdown cells. They constituted the molecular network closely related to the network defined by cell-to-cell signaling and interaction, hematological system development and function, and inflammatory response, where NF-kappaB acts as a central regulator. These results suggest that a molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in NHD. PMID- 22080357 TI - Alteration of LV end-diastolic volume by controlling the power of the continuous flow LVAD, so it is synchronized with cardiac beat: development of a native heart load control system (NHLCS). AB - There are many reports comparing pulsatile and continuous-flow left ventricular assist devices (LVAD). But continuous-flow LVAD with the pulsatile driving technique had not been tried or discussed before our group's report. We have previously developed and introduced a power-control unit for a centrifugal LVAD (EVAHEART(r); Sun Medical), which can change the speed of rotation so it is synchronized with the heart beat. By use of this unit we analyzed the end diastolic volume (EDV) to determine whether it is possible to change the native heart load. We studied 5 goats with normal hearts and 5 goats with acute LV dysfunction because of micro-embolization of the coronary artery. We used 4 modes, "circuit-clamp", "continuous", "counter-pulse", and "co-pulse", with the bypass rate (BR) 100%. We raised the speed of rotation of the LVAD in the diastolic phase with the counter-pulse mode, and raised it in the systolic phase with the co-pulse mode. As a result, the EDV decreased in the counter-pulse mode and increased in the co-pulse mode, compared with the continuous mode (p < 0.05), in both the normal and acute-heart-failure models. This result means it may be possible to achieve favorable EDV and native heart load by controlling the rotation of continuous-flow LVAD, so it is synchronized with the cardiac beat. This novel driving system may be of great benefit to patients with end-stage heart failure, especially those with ischemic etiology. PMID- 22080358 TI - Supramolecular block copolymers: graphene oxide composites for memory device applications. AB - Bistable resistive switching characteristics obtained using a supramolecular hybrid route to hydrogen-bonded block copolymers (BCP) and graphene oxide (GO) as charge storage materials are reported for write-once-read-many-times (WORM) memory devices. PMID- 22080359 TI - Changes in dry eye diagnostic status following implementation of revised Japanese dry eye diagnostic criteria. AB - PURPOSE: Our aim was to evaluate changes in dry eye diagnostic status following implementation of the new dry eye diagnostic criteria in Japan. DESIGN: This was a multicenter cross-sectional study. METHODS: We recruited 295 individuals (81 men, 214 women, average age 43.6 +/- 14.3 years) seen for general ophthalmic checkup and dry eye examinations. Using results of the Schirmer I test, tear breakup time, and fluorescein and Rose Bengal staining, patients were diagnosed as having definite dry eye (DDE), probable dry eye (PDE), or as being normal according to both the old and new Japanese dry eye diagnostic criteria. RESULTS: Mean ages of normal participants and patients with PDE and DDE were 37.0 +/- 10.4, 41.7 +/- 14.4, and 47.7 +/- 15.3 years, respectively (p < 0.001). All 37 individuals diagnosed as normal following the old criteria were also diagnosed as normal with the new diagnostic criteria. Among the 60 patients diagnosed as PDE with the old criteria, 19 (31.7%) were diagnosed as normal and 41 (68.3%) as PDE with the new diagnostic criteria. Of the 198 patients diagnosed with DDE following the old criteria, 59 (29.7%) were diagnosed as PDE and 139 (70.2%) as DDE with the new diagnostic criteria. There was no significant difference in dry eye severity index scores between the old and new diagnostic criteria. CONCLUSION: A shift in the final dry eye diagnostic status from DDE to PDE and from PDE to normal was observed with the implementation of the new dry eye diagnostic criteria, suggesting that patients at the severe end of the dry eye disease spectrum are now diagnosed as DDE disease under the new criteria. PMID- 22080360 TI - Traumatic detachment of the inferior angle of the scapula in a 5-year-old boy--a sonographic diagnosis. AB - A complete slip of the cartilage of the inferior angle of the scapula was diagnosed in a 5-year-old boy who fell inside a wooden construction at a kindergarten playground. Radiographs of the scapula were normal, and ultrasound demonstrated complete cartilage detachment, which was displaced deep and laterally. Computed tomography (CT) additionally demonstrated a thin rim of bone displaced along with the detached cartilage. Radiologic findings were confirmed during surgery. We report what we believe to be the first published case of traumatic detachment of the cartilaginous lower angle of the scapula in a child demonstrated by ultrasound. PMID- 22080361 TI - Highlights of the scientific meeting of the 18th Annual Congress of the European Society of Skeletal Radiology (ESSR) 2011. PMID- 22080362 TI - Hemi-bucket-handle tears of the meniscus: appearance on MRI and potential surgical implications. AB - OBJECTIVES: To describe a type of meniscus flap tear resembling a bucket-handle tear, named a "hemi-bucket-handle" tear; to compare its imaging features with those of a typical bucket-handle tear; and to discuss the potential therapeutic implications of distinguishing these two types of tears. MATERIALS AND METHODS: Five knee MR examinations were encountered with a type of meniscus tear consisting of a flap of tissue from the undersurface of the meniscus displaced toward the intercondylar notch. A retrospective analysis of 100 MR examinations prospectively interpreted as having bucket-handle type tears yielded 10 additional cases with this type of tear. Cases of hemi-bucket-handle tears were reviewed for tear location and orientation, appearance of the superior articular surface of the meniscus, presence and location of displaced meniscal tissue, and presence of several classic signs of bucket-handle tears. RESULTS: A total of 15/15 tears involved the medial meniscus, had tissue displaced toward the notch, and were mainly horizontal in orientation. The superior surface was intact in 11/15 (73.3%). In 1/15 (6.7%) there was an absent-bow-tie sign; 6/15 (40%) had a double-PCL sign; 14/15 (93.3%) had a double-anterior horn sign. CONCLUSION: We describe a type of undersurface flap tear, named a hemi-bucket-handle tear, which resembles a bucket-handle tear. Surgeons at our institution feel this tear would likely not heal if repaired given its predominantly horizontal orientation, and additionally speculate the tear could be overlooked at arthroscopy. Thus, we feel it is important to distinguish this type of tear from the typical bucket-handle tear. PMID- 22080363 TI - Diamond nanowires for highly sensitive matrix-free mass spectrometry analysis of small molecules. AB - This paper reports on the use of boron-doped diamond nanowires (BDD NWs) as an inorganic substrate for matrix-free laser desorption/ionization mass spectrometry (LDI-MS) analysis of small molecules. The diamond nanowires are prepared by reactive ion etching (RIE) with oxygen plasma of highly boron-doped (the boron level is 10(19) B cm(-3)) or undoped nanocrystalline diamond substrates. The resulting diamond nanowires are coated with a thin silicon oxide layer that confers a superhydrophilic character to the surface. To minimize droplet spreading, the nanowires were chemically functionalized with octadecyltrichlorosilane (OTS) and then UV/ozone treated to reach a final water contact angle of 120 degrees . The sub-bandgap absorption under UV laser irradiation and the heat confinement inside the nanowires allowed desorption/ionization, most likely via a thermal mechanism, and mass spectrometry analysis of small molecules. A detection limit of 200 zeptomole for verapamil was demonstrated. PMID- 22080364 TI - Randomized controlled trial of cough test versus no cough test in the tension free vaginal tape procedure: effect upon voiding dysfunction and 12-month efficacy. AB - INTRODUCTION AND HYPOTHESIS: This is a prospective randomized controlled trial of cough versus no cough test in the tension-free vaginal tape (TVT) procedure to determine its effect upon voiding dysfunction and 12-month efficacy. METHODS: The trial was conducted in a single tertiary urogynecology unit. Women >=21 years old with primary urodynamic stress incontinence without voiding dysfunction were considered eligible. Participants were randomized to undergo the TVT procedure using either an intraoperative cough test or using no intraoperative cough test. Our hypothesis was that postoperative voiding dysfunction would be more common in the "no cough test" arm. The primary outcome was proportion of patients successfully completing a trial of void (TOV) within 24 h of catheter removal. Efficacy at 12 months comprised the secondary outcome. Participants were randomized using a computer-generated randomization sequence by an independent party who was not the operating surgeon. Due to the nature of the intervention to be tested, neither the patients nor the operating surgeons were blinded to the randomization process during the procedure. RESULTS: This trial is reported according to the recommendations of the 2010 CONSORT statement. In total, 94 women were recruited over a 4-year study period. Of these, 92 women were randomized (47 in the "cough" group and 45 in the "no cough" group). In one case, the TVT procedure was abandoned intraoperatively, leaving 91 women who underwent analysis. There was no significant difference in the proportion of women with a successful TOV within 24 h between the two arms (79% in the "cough" group versus 71% in the "no cough" group; p = 0.47). Efficacy data at 12 months were not significantly different between groups. CONCLUSION: Our data suggest that the performance of the intraoperative cough test during the TVT procedure does not reduce the incidence of postoperative voiding dysfunction (as determined by successful TOV within 24 h) nor affect efficacy. The removal of the cough test from the standard TVT technique may be appropriate. PMID- 22080365 TI - Solvent-solvent and solvent-solute interactions in a 3D chloroform clathrate with diorganotin macrocycles in the nano-sized pores. AB - A 3D clathrate of deuterochloroform molecules was formed in the presence of nano sized macrocyclic molecules. PMID- 22080366 TI - Reinforcement sensitivity and risk for psychopathology following exposure to violence: a vulnerability-specificity model in Latino youth. AB - Urban Latino youth are exposed to high rates of violence, which increases risk for diverse forms of psychopathology. The current study aims to increase specificity in predicting responses by testing the hypothesis that youths' reinforcement sensitivity-behavioral inhibition (BIS) and behavioral approach (BAS)-is associated with specific clinical outcomes and increases risk for the development of such problems following exposure to violence. Utilizing a short term longitudinal design, Latino youth (N = 168) provided reports of BIS/BAS and emotional/behavioral problems at Time 1, exposure to violence between Time 1 and Time 2, and clinical symptoms at Time 2. Results suggested that reinforcement sensitivity moderated the relation between violence exposure and psychopathology, such that increasing levels of BIS were associated with elevated risk for internalizing and posttraumatic stress symptoms following exposure to violence whereas BAS increased risk for externalizing problems. The importance of building on existing knowledge to understand minority youth psychopathology is discussed. PMID- 22080367 TI - Psychological morbidity in children 18 months after Kashmir Earthquake of 2005. AB - A severe earthquake occurred in Kashmir in 2005. The epicentre was close to Muzzafarabad. We collected data on over 1,100 children 18 months after the earthquake to look at symptoms of PTSD and behavioural and emotional problems using well established questionnaires. We found that 64.8% of children had significant symptoms of PTSD. Girls were more likely to suffer from these symptoms. The proportion of children suffering from emotional and behaviour difficulties was 34.6%. This percentage was not different from other studies of children from Pakistan within areas which were not affected by the earthquake. The rate of emotional symptoms was higher in girls while hyperactivity was more frequent in boys. This pattern is similar to other studies from across the world. PMID- 22080369 TI - Characterization of novel calmodulin binding domains within IQ motifs of IQGAP1. AB - IQ motif-containing GTPase-activating protein 1 (IQGAP1), which is a well-known calmodulin (CaM) binding protein, is involved in a wide range of cellular processes including cell proliferation, tumorigenesis, adhesion, and migration. Interaction of IQGAP1 with CaM is important for its cellular functions. Although each IQ domain of IQGAP1 for CaM binding has been characterized in a Ca(2+) dependent or -independent manner, it was not clear which IQ motifs are physiologically relevant for CaM binding in the cells. In this study, we performed immunoprecipitation using 3xFLAGhCaM in mammalian cell lines to characterize the domains of IQGAP1 that are key for CaM binding under physiological conditions. Interestingly, using this method, we identified two novel domains, IQ(2.7-3) and IQ(3.5-4.4), within IQGAP1 that were involved in Ca(2+)-independent or -dependent CaM binding, respectively. Mutant analysis clearly showed that the hydrophobic regions within IQ(2.7-3) were mainly involved in apoCaM binding, while the basic amino acids and hydrophobic region of IQ(3.5 4.4) were required for Ca(2+)/CaM binding. Finally, we showed that IQ(2.7-3) was the main apoCaM binding domain and both IQ(2.7-3) and IQ(3.5-4.4) were required for Ca(2+)/CaM binding within IQ(1-2-3-4). Thus, we identified and characterized novel direct CaM binding motifs essential for IQGAP1. This finding indicates that IQGAP1 plays a dynamic role via direct interactions with CaM in a Ca(2+) dependent or -independent manner. PMID- 22080368 TI - The regulation of food intake in mammalian hibernators: a review. AB - One of the most profound hallmarks of mammalian hibernation is the dramatic reduction in food intake during the winter months. Several species of hibernator completely cease food intake (aphagia) for nearly 7 months regardless of ambient temperature and in many cases, whether or not food is available to them. Food intake regulation has been studied in mammals that hibernate for over 50 years and still little is known about the physiological mechanisms that control this important behavior in hibernators. It is well known from lesion experiments in non-hibernators that the hypothalamus is the main brain region controlling food intake and therefore body mass. In hibernators, the regulation of food intake and body mass is presumably governed by a circannual rhythm since there is a clear seasonal rhythm to food intake: animals increase food intake in the summer and early autumn, food intake declines in autumn and actually ceases in winter in many species, and resumes again in spring as food becomes available in the environment. Changes in circulating hormones (e.g., leptin, insulin, and ghrelin), nutrients (glucose, and free fatty acids), and cellular enzymes such as AMP-activated protein kinase (AMPK) have been shown to determine the activity of neurons involved in the food intake pathway. Thus, it appears likely that the food intake pathway is controlled by a variety of inputs, but is also acted upon by upstream regulators that are presumably rhythmic in nature. Current research examining the molecular mechanisms and integration of environmental signals (e.g., temperature and light) with these molecular mechanisms will hopefully shed light on how animals can turn off food intake and survive without eating for months on end. PMID- 22080370 TI - Analysis of Arabidopsis transcription factor families revealed extensive capacity for cell-to-cell movement as well as discrete trafficking patterns. AB - In plants, cell-to-cell communication is pivotal for the orchestration of cell fate determination, organ development, and the integration of whole plant physiology. One of the strategies for intercellular communication uses symplasmic communication channels, called plasmodesmata (PD). These PD establish unique cytoplasmic channels for the intercellular exchange not only of metabolites and small signaling molecules, but also of regulatory proteins and RNAs to allow for local orchestration of development and physiology. A number of non-cell autonomous transcription factors (NCATFs) have been shown to function in the coordination of specific regulatory networks. To further explore the potential of such NCATFs, a genome-wide screen was performed on the transcription factor (TF) families in Arabidopsis. We here report that, among the 76 TFs examined, 22 were shown to move beyond their sites of transcription in the root apex; these NCATFs belonged to 17 TF families, including homeobox, GRAS, and MYB. Expression studies performed on variously-sized mCherry constructs identified a range of PD size exclusion limits within tissues of the root. In addition, our studies showed that actual protein level was an important factor controlling the range of TF intercellular movement. Interestingly, our studies on CAPRICE movement revealed tissue-specificity with respect to the mode of intercellular trafficking. These findings are discussed with respect to the regulation between cell-autonomous or non-cell-autonomous action. PMID- 22080371 TI - The murine goblet cell protein mCLCA3 is a zinc-dependent metalloprotease with autoproteolytic activity. AB - Several members of the CLCA family of proteins, originally named chloride channels, calcium-activated, have been shown to modulate chloride conductance in various cell types via an unknown mechanism. Moreover, the human (h) hCLCA1 is thought to modulate the severity of disease in asthma and cystic fibrosis (CF) patients. All CLCA proteins are post-translationally cleaved into two subunits, and recently, a conserved HEXXH zinc-binding amino acid motif has been identified, suggesting a role for CLCA proteins as metalloproteases. Here, we have characterized the cleavage and autoproteolytic activity of the murine model protein mCLCA3, which represents the murine orthologue of human hCLCA1. Using crude membrane fractions from transfected HEK293 cells, we demonstrate that mCLCA3 cleavage is zinc-dependent and exclusively inhibited by cation-chelating metalloprotease inhibitors. Cellular transport and secretion were not affected in response to a cleavage defect that was introduced by the insertion of an E157Q mutation within the HEXXH motif of mCLCA3. Interspecies conservation of these key results was further confirmed with the porcine (p) orthologue of hCLCA1 and mCLCA3, pCLCA1. Importantly, the mCLCA3E157Q mutant was cleaved after co transfection with the wild-type mCLCA3 in HEK293 cells, suggesting that an intermolecular autoproteolytic event takes place. Edman degradation and MALDI-TOF MS of the protein fragments identified a single cleavage site in mCLCA3 between amino acids 695 and 696. The data strongly suggest that secreted CLCA proteins have zinc-dependent autoproteolytic activity and that they may cleave additional proteins. PMID- 22080372 TI - The pleiohomeotic functions as a negative regulator of Drosophila even-skipped gene during embryogenesis. AB - Polycomb group (PcG) proteins maintain the spatial expression patterns of genes that are involved in cell-fate specification along the anterior-posterior (A/P) axis. This repression requires cis-acting silencers, which are called PcG response elements (PREs). One of the PcG proteins, Pleiohomeotic (Pho), which has a zinc finger DNA binding protein, plays a critical role in recruiting other PcG proteins to bind to PREs. In this study, we characterized the effects of a pho mutation on embryonic segmentation. pho maternal mutant embryos showed various segmental defects including pair-rule gene mutant patterns. Our results indicated that engrailed and even-skipped genes were misexpressed in pho mutant embryos, which caused embryonic segment defects. PMID- 22080373 TI - Synchronization of cell cycle of Saccharomyces cerevisiae by using a cell chip platform. AB - Cell synchrony is a critical requirement for the study of eukaryotic cells. Although several chemical and genetic methods of cell cycle synchronization are currently available, they have certain limitations, such as unnecessary perturbations to cells. We developed a novel cell cycle synchronization method that is based on a cell chip platform. The budding yeast, Saccharomyces cerevisiae, is a simple but useful model system to study cell biology and shares many similar features with higher eukaryotic cells. Single yeast cells were individually captured in the wells of a specially designed cell chip platform. When released from the cell chip, the yeast cells were synchronized, with all cells in the G1 phase. This method is non-invasive and causes minimal chemical and biological damage to cells. The capture and release of cells using cells chips with microwells of specific dimensions allows for the isolation of cells of a particular size and shape; this enables the isolation of cells of a given phase, because the size and shape of yeast cells vary with the phase of the cell cycle. To test the viability of synchronized cells, the yeast cells captured in the cell chip platform were assessed for response to mating pheromone (alpha factor). The synchronized cells isolated using the cell chip were capable of mediating the mating signaling response and exhibited a dynamic and robust response behavior. By changing the dimensions of the well of the cell chip, cells of other cell cycle phases can also be isolated. PMID- 22080374 TI - Quantitative trait loci for cold tolerance of rice recombinant inbred lines in low temperature environments. AB - Low temperature is one of the major environmental stresses in rice cultivation in high-altitude and high-latitude regions. In this study, we cultivated a set of recombinant inbred lines (RIL) derived from Dasanbyeo (indica) / TR22183 (japonica) crosses in Yanji (high-latitude area), Kunming (high-altitude area), Chuncheon (cold water irrigation) and Suwon (normal) to evaluate the main effects of quantitative trait loci (QTL) and epistatic QTL (E-QTL) with regard to their interactions with environments for cold-related traits. Six QTLs for spikelet fertility (SF) were identified in three cold treatment locations. Among them, four QTLs on chromosomes 2, 7, 8, and 10 were validated by several near isogenic lines (NILs) under cold treatment in Chuncheon. A total of 57 QTLs and 76 E-QTLs for nine cold-related traits were identified as distributing on all 12 chromosomes; among them, 19 QTLs and E-QTLs showed significant interactions of QTLs and environments (QEIs). The total phenotypic variation explained by each trait ranged from 13.2 to 29.1% in QTLs, 10.6 to 29.0% in EQTLs, 2.2 to 8.8% in QEIs and 1.0% to 7.7% in E-QTL * environment interactions (E-QEIs). These results demonstrate that epistatic effects and QEIs are important properties of QTL parameters for cold tolerance at the reproductive stage. In order to develop cold tolerant varieties adaptable to wide-ranges of cold stress, a strategy facilitating marker-assisted selection (MAS) is being adopted to accumulate QTLs identified from different environments. PMID- 22080376 TI - Synthesis, characterization and photophysical properties of PPh2-C2-(C6H4)n-C2 PPh2 based bimetallic Au(I) complexes. AB - A family of the diphosphines PPh(2)C(2)(C(6)H(4))(n)C(2)PPh(2) (n = 0-3), which possess a dialkynyl-arene spacer between the phosphorus atoms, was used for the synthesis of a series of bimetallic gold(I) complexes 1-7. Unlike the corresponding polynuclear Au(i) clusters, which show unique phosphorescence, 1-7 reveal dual emissions consisting of fluorescence and phosphorescence. The results are rationalized, in a semi-quantitative manner, by the trace (1-3) to zero (4-7) contribution of MLCT varying with the number of conjugated phenylene rings. As a result, unlike typical polynuclear Au(I) clusters with 100% triplet state population, the rate constant of the S(1)->T(1) intersystem crossing is drastically reduced to 10(9) s(-1) (4-7)-10(10) s(-1) (1-3), so that the fluorescence radiative decay rate can compete or even dominates. The drastic O(2) quenching of phosphorescence demonstrates the unprotected nature of the emission chromophores in 1-7, as opposed to the well protected, O(2) independent phosphorescence in most multimetallic Au(I) clusters. PMID- 22080375 TI - Structural insights into the conformational diversity of ClpP from Bacillus subtilis. AB - ClpP is a cylindrical protease that is tightly regulated by Clp-ATPases. The activation mechanism of ClpP using acyldepsipeptide antibiotics as mimics of natural activators showed enlargement of the axial entrance pore for easier processing of incoming substrates. However, the elimination of degradation products from inside the ClpP chamber remains unclear since there is no exit pore for releasing these products in all determined ClpP structures. Here we report a new crystal structure of ClpP from Bacillus subtilis, which shows a significantly compressed shape along the axial direction. A portion of the handle regions comprising the heptameric ring-ring contacts shows structural transition from an ordered to a disordered state, which triggers the large conformational change from an extended to an overall compressed structure. Along with this structural change, 14 side pores are generated for product release and the catalytic triad adopts an inactive orientation. We have also determined B. subtilis ClpP inhibited by diisopropylfluoro-phosphate and analyzed the active site in detail. Structural information pertaining to several different conformational steps such as those related to extended, ADEP-activated, DFP-inhibited and compressed forms of ClpP from B. subtilis is available. Structural comparisons suggest that functionally important regions in the ClpP-family such as N-terminal segments for the axial pore, catalytic triads, and handle domains for the product releasing pore exhibit intrinsically dynamic and unique structural features. This study provides valuable insights for understanding the enigmatic cylindrical degradation machinery of ClpP as well as other related proteases such as HslV and the 20S proteasome. PMID- 22080377 TI - Value of percutaneous radiofrequency ablation with or without percutaneous vertebroplasty for pain relief and functional recovery in painful bone metastases. AB - OBJECTIVE: To evaluate the effectiveness of percutaneous radiofrequency (RF) ablation with or without percutaneous vertebroplasty (PV) on pain relief, functional recovery and local recurrence at 6 months' follow-up (FU), in patients with painful osseous metastases. MATERIALS AND METHODS: Thirty RF ablations were performed in 24 patients (mean age: 61 years) with bone metastases. Half of the patients had an additional PV. The primary end point was pain relief evaluated by a visual analogue scale (VAS) before treatment, and at 1 and 6 months' FU. Functional outcome was assessed according to the evolution of their ability to walk at 6 months' FU. Imaging FU was available in 20 out of 24 patients with a mean delay of 4.7 months. RESULTS: Reduction of pain was obtained at 6 months FU in 81% of cases (15 out of 18). Mean pretreatment VAS was 6.4 (+/-2.7). Mean VAS was 1.9 (+/-2.4) at 1 month FU, and 2.3 (+/-2.9) at 6 months' FU. Pain was significantly reduced at 6 months FU (mean VAS reduction = 4.1; P < 0.00001). Functional improvement was obtained in 74% of the cases. Major complications rate was 12.5 % (3 out of 24) with 2 skin burns, and 1 case of myelopathy. Local tumour recurrence or progression was recorded in 5 cases. CONCLUSION: Radiofrequency ablation is an effective technique in terms of pain relief and functional recovery for the treatment of bone metastases, which provides a relatively low rate of local recurrence. PMID- 22080378 TI - 25-Hydroxyvitamin-D3 levels are positively related to subsequent cortical bone development in childhood: findings from a large prospective cohort study. AB - In exploring relationships between vitamin D status in childhood and cortical bone, little relationship was observed with plasma concentrations of 25 hydroxyvitamin-D(2) [25(OH)D(2)], whereas 25-hydroxyvitamin-D(3) [25(OH)D(3)] was positively related to cortical bone mineral content (BMC(C)) and cortical thickness, suggesting D(3) exerts a beneficial effect on cortical bone development in contrast to D(2). INTRODUCTION: The study is aimed to determine whether vitamin D status in childhood is related to cortical bone development by examining prospective relationships between plasma concentrations of 25(OH)D(2) and 25(OH)D(3) at 7.6, 9.9 or 11.8 years and peripheral quantitative computed tomography (pQCT) measurements of the mid-tibia at age 15.5 years, in children from the Avon Longitudinal Study of Parents and Children. METHODS: Relationships between vitamin D status and pQCT outcomes were analysed by bootstrap linear regression, adjusted for age, sex, body composition, socioeconomic position and physical activity, in 2,247 subjects in whom all covariates were available. 25(OH)D(3) was also adjusted for season and 25(OH)D(2), and 25(OH)D(2) for 25(OH)D(3). RESULTS: 25(OH)D(3) was positively related to BMC(C) [0.066(0.009,0.122), P = 0.02], whereas no association was seen with 25(OH)D(2) [ 0.008(-0.044,0.027), P = 0.7] [beta (with 95% CI) represents SD changes per doubling of vitamin D], P = 0.03 for difference in associations of 25(OH)D(2) and 25(OH)D(3) with BMC(C). There were also differences in associations with cortical geometry, since 25(OH)D(3) was positively related to cortical thickness [0.11(0.04, 0.19), P = 0.002], whereas no association was seen with 25(OH)D(2) [ 0.04(-0.08,0.009), P = 0.1], P = 0.0005 for difference. These relationships translated into differences in biomechanical strength as reflected by buckling ratio, which was positively related to 25(OH)D(2) [0.06(0.01,0.11), P = 0.02] indicating less resistance to buckling, but inversely related to 25(OH)D(3) [ 0.1(-0.19,-0.02), P = 0.03], P = 0.001 for difference. CONCLUSIONS: In contrast to 25(OH)D(2), 25(OH)D(3) was positively related to subsequent cortical bone mass and predicted strength. In vitamin D-deficient children in whom supplementation is being considered, our results suggest that D(3) should be used in preference to D(2). PMID- 22080380 TI - Oxygen and light sensitive field-effect transistors based on ZnO nanoparticles attached to individual double-walled carbon nanotubes. AB - The attachment of semiconducting nanoparticles to carbon nanotubes is one of the most challenging subjects in nanotechnology. Successful high coverage attachment and control over the charge transfer mechanism and photo-current generation open a wide field of new applications such as highly effective solar cells and fibre enhanced polymers. In this work we study the charge transfer in individual double walled carbon nanotubes highly covered with uniform ZnO nanoparticles. The synthetic colloidal procedure was chosen to avoid long-chained ligands at the nanoparticle-nanotube interface. The resulting composite material was used as conductive channel in a field-effect transistor device and the electrical photo response was analysed under various conditions. By means of the transfer characteristics we could elucidate the mechanism of charge transfer from non covalently attached semiconducting nanoparticles to carbon nanotubes. The role of positive charges remaining on the nanoparticles is discussed in terms of a gating effect. PMID- 22080379 TI - Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men? AB - In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss. INTRODUCTION: Experimental evidence suggests that angiotensin II promotes bone loss by its effects on osteoblasts. It is therefore plausible that ACE inhibitor and ARB may reduce rates of bone loss. The objective of this study is to examine the independent effects of ACE inhibitor and ARB on bone loss in older men. METHODS: Out of 5,995 American men (87.2%) aged >=65 years, 5,229 were followed up for an average of 4.6 years in a prospective six center cohort study-The Osteoporotic Fractures in Men Study (MrOS). Bone mineral densities (BMD) at total hip, femoral neck, and trochanter were measured by Hologic densitometer (QDR 4500) at baseline and year 4. RESULTS: Out of 3,494 eligible subjects with complete data, 1,166 and 433 subjects reported use of ACE inhibitors and ARBs, respectively. When compared with nonusers, continuous use of ACE inhibitors was associated with a small (0.004 g/cm(2)) but significant increase in the average rate of BMD loss at total hip and trochanter over 4 years after adjustment for confounders. Use of ARB was not significantly associated with bone loss. CONCLUSION: Use of ACE inhibitors but not ARB may marginally increase bone loss in older men. PMID- 22080381 TI - Glioblastoma multiforme with very rapid growth and long-term survival in children. PMID- 22080382 TI - The evaluation of function and the ultrasonographic picture of thyroid in children treated for medulloblastoma. AB - PURPOSE: Medulloblastoma (MB) is one of the most frequent and sensitive to radiation aggressive brain tumor in children. Abnormalities of the thyroid function are common complications of head and neck irradiation for childhood cancer. The aim of this study was to assess thyroid function in children treated for medulloblastoma according to the treatment protocol phase. PATIENTS AND METHODS: Twenty-three children with MB were enrolled to this study. All patients underwent chemotherapy and radiotherapy to the whole craniospinal axis and boost with the conformal therapy restricted to the tumor bed to a total dose of 54 Gy. Thyroid function was evaluated based on thyroid-stimulating hormone (TSH), free thyroxine (fT4) levels controlled before MB treatment, directly after irradiation and at the end of the treatment protocol. Ultrasonography has been used to detect parenchymal abnormalities. RESULTS: All patients presented normal thyroid hormone range before chemotherapy. Hypothyroidism was found in 12 patients in the course of treatment, in 2 patients hormone deficits diagnosed directly after irradiation, in 10 patients such condition was observed at the end of the whole therapy. All of these patients needed thyroid hormone substitution. None of them presented clinical symptoms of hypothyroidism. Ultrasound-detected abnormalities have been found in 20 patients. CONCLUSIONS: It is crucial to monitor the functions of the thyroid gland in children treated for medulloblastoma because of the high risk of hypothyroidism resulting from the treatment. The change in the echogenicity of the thyroid gland may be an early marker for a dysfunction of this organ in children treated for medulloblastoma. PMID- 22080383 TI - From migraine to epilepsy: a threshold mechanism? AB - A 67-year-old man complained of a transient blurring of vision in his right visual field lasting 30 min followed by headache. Two weeks later, the visual disturbance changed its pattern; it was described as the occurrence of brown round-shaped images in the right visual field spinning and turning for few seconds. This evolution from visual aura to visual seizures, with video-EEG correlation, supports the hypothesis of modification in threshold of cortical hyperexcitability from migraine to epilepsy. PMID- 22080384 TI - Upconversion-powered photoelectrochemistry. AB - Upconversion photochemistry occurring between palladium(II) octaethylporphyrin (PdOEP, 1) and 9,10-diphenylanthracene (DPA, 2) in toluene successfully sensitizes nanostructured WO(3) photoanodes (E(g) = 2.7 eV) to sub-bandgap non coherent green photons at low power density. PMID- 22080385 TI - Acceptability of circumcision among clients of female sex worker in Hong Kong. AB - Clients of female sex workers (CFSW) are at high risk of HIV transmission. Circumcision reduces the risk of heterosexual transmission of HIV. A total of 353 CFSW were interviewed using a combined interviewer-computer-assisted method. Amongst the participants, 28.0% were circumcised, whilst 63.8% of the uncircumcised participants were willing to take up circumcision (conditioned on being briefed about a 50% potential risk reduction effect). In a stepwise logistic regression model, frequency of patronizing female sex workers and factors related to the Health Belief Model were significantly associated with conditional willingness. Amongst uncircumcised participants, 20.9% anticipated risk compensation (i.e. would use condoms less frequently after being circumcised). Adjusting for background variables, inconsistent condom use during commercial sex and self-reported STD history in the last 6 months were significantly associated with anticipated risk compensation. It is feasible to promote circumcision among CFSW but such programs also need to promote condom use. PMID- 22080386 TI - 'A virus and nothing else': the effect of ART on HIV-related stigma in rural South Africa. AB - While the World Health Organization acknowledges the potential of antiretroviral therapy to reduce HIV-related stigma, few studies examine the nature of this linkage. This article discusses the connection between ART and HIV-related stigma, using qualitative analysis of interviews with HIV-positive adults at a rural South African clinic. The data has two main implications for ART's role in stigma reduction: it strengthens the plausibility that ART can reduce stigma through weakening HIV/AIDS's link with disfigurement and death, and shows that ART enables the establishment of spaces for support, which reduce stigma through normalization of the disease. PMID- 22080387 TI - Preschoolers' psychosocial problems: in the eyes of the beholder? Adding teacher characteristics as determinants of discrepant parent-teacher reports. AB - In this study, we explored informant characteristics as determinants of parent teacher disagreement on preschoolers' psychosocial problems. Teacher characteristics were included in the analyses, in addition to child and parent factors. Psychosocial problems of 732 4-year olds from a Norwegian community sample were assessed by parents and teachers (CBCL-TRF). Furthermore, teachers reported on their education, experience and relationship to the child. Parental stress and psychopathology were also measured. Teachers rated children considerably lower than their parents did, especially on internalizing problems. When teachers rated more child problems, this was strongly associated with conflict in the teacher-child relationship, which predicted disagreement more than other factors. The highest agreement was on boys' externalizing problems. Girls' behavior was rated much lower by teachers than boys' behavior compared to parents' ratings. Possible teacher perception biases are discussed, such as teacher-child conflict, non-identification of internalizing problems, and same gender child preference. PMID- 22080388 TI - Lithium amidoborane, a highly chemoselective reagent for the reduction of alpha,beta-unsaturated ketones to allylic alcohols. AB - Lithium amidoborane (LiNH(2)BH(3), LiAB for short), is capable of chemoselectively reducing alpha,beta-unsaturated ketones to the corresponding allylic alcohols at ambient temperature. A mechanistic study shows that the reduction is via a double hydrogen transfer process. The protic H(N) and hydridic H(B) in amidoborane add to the O and C sites of the carbonyl group, respectively. PMID- 22080389 TI - Gastric cancer detection using MDCT compared with 2D axial CT: diagnostic accuracy of three different reconstruction techniques. AB - PURPOSE: To assess the diagnostic accuracy of different reconstruction techniques using MDCT for gastric cancer detection compared with 2D axial CT. MATERIALS AND METHODS: During 7 months, we performed CT examinations of 104 consecutive patients with gastric cancer and of a control group composed of 35 patients without gastric disease. All gastric cancer was pathologically proven by endoscopy and surgery. Among 104 patients with gastric cancer, 63 patients had early gastric cancer (EGC). Two radiologists retrospectively and independently interpreted the axial CT and three different reconstruction techniques including multiplanar reformation (MPR), transparent imaging (TI), and virtual gastroscopy (VG), using a commercially available, 3D workstation. They graded the presence or absence of gastric cancer in each image sets using a five-point scale and, if present, they assessed its location. Diagnostic accuracy was compared using the area under the receiver operating characteristic curve (Az) for both gastric cancer and only EGC. Sensitivity and specificity were also calculated for each image technique. The k statistics were used to determine inter-observer agreement. RESULTS: The diagnostic accuracy for overall gastric cancer detection for each of the image sets was as follows: 2D axial CT (Az = 0.858); MPR (Az = 0.879); TI (Az = 0.873); and VG (Az = 0.928). VG had significantly better performance than 2D axial CT (p = 0.016). The sensitivity and specificity were as follows: 76.7% and 82.9% in axial CT; 79.6% and 85.7% in MPR; 91.3% and 80% in TI; and 95.1% and 74.3% in VG. In EGC, the diagnostic performance for its detection was as follows: axial CT (Az = 0.777); MPR (Az = 0.811); TI (Az = 0.825); and VG (Az = 0.896). VG had significantly better performance than both 2D axial CT (P = 0.006) and MRP (P = 0.038). The sensitivity and specificity were as follows: 62.9% and 82.9% in axial CT; 67.7% and 85.7% in MPR; 85.5% and 80% in TI; and 91.9% and 74.3% in VG. The inter-observer agreement showed substantial agreement (kappa = 0.67-0.75). CONCLUSION: Among the different reconstruction techniques, VG accurately detects gastric cancer and is especially useful for EGC compared with 2D axial CT. PMID- 22080390 TI - Luminescent Ir(III) complexes containing benzothiazole-based tridentate ligands: synthesis, characterization, and application to organic light-emitting diodes. AB - Ir(III) complexes that contain benzothiazole-based tridentate ligands were synthesized and their crystal structures and luminescent properties were examined. A neutral complex had a high quantum yield (89%) and performed well as an emissive material for organic light-emitting diodes. PMID- 22080391 TI - Influence of postoperative enteral nutrition on cellular immunity. A random double-blinded placebo controlled clinical trial. AB - PURPOSE: The aim of this study was to discover if the cellular immunological response is different in patients receiving early postoperative enteral nutrition compared to patients who only receive "water". METHODS: In a random double-blind prospective trial, 30 patients received Nutridrink(r) and 30 patients received placebo (water) through a nasoduodenal tube from the day of operation to the fourth postoperative day. Leukocyte differential count was examined preoperatively, and on the first, third, and seventh postoperative days. Subpopulations of lymphocytes were flow cytometrically analysed. IL-1ra and soluble IL-2R were investigated by use of an enzyme-linked immunosorbent assay. RESULTS: In the enteral nutrition group, a significantly larger number of circulating monocytes and NK-cells and a significantly larger expression of HLA DR were found. In the nutrition group, a tendency to larger numbers of T lymphocyte subpopulations was found. No difference in IL-1ra and soluble IL-2R was found between the groups. CONCLUSION: Early postoperative enteral nutrition has an important influence on the immediate unspecific cellular immunity and an activating effect on the specific cellular immunity compared to "no food". PMID- 22080392 TI - Can we predict pathologic complete response before surgery for locally advanced rectal cancer treated with preoperative chemoradiation therapy? AB - BACKGROUND: Pathologic complete response has been proven to have oncological benefits for locally advanced rectal cancer treated with chemoradiation therapy. The aims of this study are to analyze and determine the factors to predict pathologic complete response for patients treated with preoperative neoadjuvant therapy. METHODS: Patients with biopsy-proven, locally advanced rectal cancer were treated neoadjuvantly followed by radical surgical resection. Tumors were re assessed after completing chemoradiation, including pelvic magnetic resonance images, colonoscopic examination, and re-biopsy. The results of examination were compared with the final pathologic status. RESULTS: A retrospective chart review of 166 patients was conducted. Twenty-five patients (15.1%) had pathologic complete response after chemoradiation. The 5-year overall survival rates were better in the complete response group than the residual tumor group (91.1% vs. 70.8%; P = 0.047), and there were also significant differences in the 5-year disease-free survival rates between these two groups (91.1% vs. 70.2%; P = 0.027). The prediction rates for pathologic complete response by re-biopsy, magnetic resonance images, and colonoscopy were 21.4%, 33.3%, and 53.8%, respectively. In addition, when we further combine the results of colonoscopic findings and re-biopsy, the prediction rate for pathologic complete response reached 77.8% (P = 0.009). CONCLUSIONS: Combining the results of the re-biopsy and post-treatment colonoscopic findings, we can achieve a good prediction rate for pathologic complete response. Post-treatment magnetic resonance images are not useful tools in predicting tumor clearance following chemoradiation. PMID- 22080393 TI - Enhancement of enantioselectivity by alcohol additives in asymmetric hydrogenation with bis(oxazolinyl)phenyl ruthenium catalysts. AB - Bis(oxazolinyl)phenyl ruthenium(II) complexes were found to catalyze asymmetric hydrogenation of ketones, in which chiral bulky alcohol additives showed significant enhancement of enantioselectivity even in protic solvents. PMID- 22080394 TI - Central pontine and extrapontine myelinolysis associated with acute hepatic dysfunction. AB - Central pontine myelinolysis and extrapontine myelinolysis are rare demyelinating diseases of the central nervous system. These diseases are related frequently to rapid correction of hyponatremia. They have also been described in association with other underlying conditions such as alcoholism and malnutrition. In the present study, we report a case of central pontine and extrapontine myelinolysis with acute hepatic dysfunction. The patient had no apparent evidence of hyponatremia and no history of alcohol abuse. On admission, the patient was lethargic; dysphagia, dysarthria, and quadriplegia were noted. Laboratory examination showed significantly increased transaminase without hyponatremia. Magnetic resonance imaging revealed abnormal signal intensities in the pons and thalamus. Consciousness level and clinical symptoms improved gradually within a week. We suggest that acute hepatic dysfunction may play an important role in the development of central pontine myelinolysis and extrapontine myelinolysis. PMID- 22080396 TI - Development and psychometric evaluation of the Social Justice Scale (SJS). AB - The study describes the development of the Social Justice Scale (SJS). Practitioners, educators, students, and other members of the community differ on their attitudes and values regarding social justice. It is important to assess, not only individuals' attitudes and values around social values, but also other constructs that might be related to social justice behaviors. The implication of Ajzen in Organizational Behavior and Human Decision Processes 50:179-211, (1991) theory of planned behavior suggests that attitudes, perceived behavioral control, and social norms predict intentions, which then lead to behaviors. A scale was designed to measure social justice-related values, attitudes, perceived behavioral control, subjective norms, and intentions based on a four-factor conception of Ajzen's theory. Confirmatory factor analysis and analyses for reliability and validity were used to test the properties of the scale. PMID- 22080397 TI - A longitudinal process analysis of mother-child emotional relationships in a rural Appalachian European American community. AB - This prospective longitudinal study examines emotional relationships in 58 Appalachian mother-child dyads observed at home at 5 and 20 months. Between infancy and toddlerhood, 3 of 4 dimensions of dyadic emotional relationships were stable, and three remained continuous in their mean level. Increasing maternal age was associated with greater maternal sensitivity and structuring and with more responsive and involving children. Marital status and father presence in the home as well as maternal openness, parenting knowledge, investment, and satisfaction accounted for effects of maternal age on dyadic emotional relationships. This longitudinal process analysis provides unique insights into temporal dynamics of mother-child emotional relationships and their determinants in an underserved and underresearched US community. Implications for community specific interventions are discussed. PMID- 22080398 TI - Visual backward masking performance in young adult emmetropes and myopes. AB - PURPOSE: To investigate how temporal processing is altered in myopia and during myopic progression. METHODS: In backward visual masking, a target's visibility is reduced by a mask presented quickly after the target. Thirty emmetropes, 40 low myopes, and 22 high myopes aged 18 to 26 years completed location and resolution masking tasks. The location task examined the ability to detect letters with low contrast and large stimulus size. The resolution task involved identifying a small letter and tested resolution and color discrimination. Target and mask stimuli were presented at nine short interstimulus intervals (12 to 259 ms) and at 1000 ms (long interstimulus interval condition). RESULTS: In comparison with emmetropes, myopes had reduced ability in both locating and identifying briefly presented stimuli but were more affected by backward masking for a low contrast location task than for a resolution task. Performances of low and high myopes, as well as stable and progressing myopes, were similar for both masking tasks. Task performance was not correlated with myopia magnitude. CONCLUSIONS: Myopes were more affected than emmetropes by masking stimuli for the location task. This was not affected by magnitude or progression rate of myopia, suggesting that myopes have the propensity for poor performance in locating briefly presented low contrast objects at an early stage of myopia development. PMID- 22080399 TI - Driving speed is altered by monocular neutral density filters: the Enright phenomenon. AB - PURPOSE: An observer, looking sideways from a moving vehicle, while wearing a neutral density (ND) filter over one eye, can have a distorted perception of speed, known as the Enright phenomenon. The purpose of this study was to determine how the Enright phenomenon influences driving behavior. METHODS: A geometric model of the Enright phenomenon was developed. Ten young, visually normal, participants (mean age = 25.4 years) were tested on a straight section of a closed driving circuit and instructed to look out of the right side of the vehicle and drive at either 40 km/h or 60 km/h under the following binocular viewing conditions: with a 0.9 ND filter over the left eye (leading eye); 0.9 ND filter over the right eye (trailing eye); 0.9 ND filters over both eyes, and with no filters over either eye. The order of filter conditions was randomized and the speed driven recorded for each condition. RESULTS: Speed judgments did not differ significantly between the two baseline conditions (no filters and both eyes filtered) for either speed tested. For the baseline conditions, when subjects were asked to drive at 60 km/h, they matched this speed well (61 +/- 10.2 km/h) but drove significantly faster than requested (51.6 +/- 9.4 km/h) when asked to drive at 40 km/h. Subjects significantly exceeded baseline speeds by 8.7 +/- 5.0 km/h, when the trailing eye was filtered and traveled slower than baseline speeds by 3.7 +/- 4.6 km/h when the leading eye was filtered. CONCLUSIONS: This is the first quantitative study demonstrating how the Enright effect can influence perceptions of driving speed and demonstrates that monocular filtering of an eye can significantly impact driving speeds, albeit to a lesser extent than predicted by geometric models of the phenomenon. PMID- 22080395 TI - Local renin-angiotensin systems in the genitourinary tract. AB - Local renin-angiotensin systems are common throughout the human body. Recent evidence supports the existence of such local renin-angiotensin systems in the penis, clitoris, bladder, ureter, internal anal sphincter, and urethral sphincter. Beyond its role in regulating blood pressure through its effects on vascular tone, sodium balance, and fluid homeostasis, angiotensin II serves a key role in affecting physiologic and pathophysiologic activities of the genitourinary tract. Just as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are used for the treatment and prevention of heart disease and vascular disease, inhibition of excessive angiotensin II activity may be potentially useful for the treatment of urologic disorders. PMID- 22080401 TI - The gap junction protein Cx43 is involved in the bone-targeted metastatic behaviour of human prostate cancer cells. AB - For decades, cancer was associated with gap-junction defects. However, more recently it appeared that the gap junction proteins (connexins) could be re expressed and participate to cancer cell dissemination during the late stages of tumor progression. Since primary tumors of prostate cancer (PCa) are known to be connexin deficient, it was interesting to verify whether their bone-targeted metastatic behaviour could be influenced by the re-expression of the connexin type (connexin43) which is originally present in prostate tissue and highly expressed in bone where it participates to the differentiation of osteoblastic cells. Thus, we investigated the effect of the increased Cx43 expression, by retroviral infection, on the metastatic behaviour of two well-characterized cell lines (PC-3 and LNCaP) representing different stages of PCa progression. It appeared that Cx43 differently behaved in those cell lines and induced different phenotypes. In LNCaP, Cx43 was functional, localized at the plasma membrane and its high expression was correlated with a more aggressive phenotype both in vitro and in vivo. In particular, those Cx43-expressing LNCaP cells exhibited a high incidence of osteolytic metastases generated by bone xenografts in mice. Interestingly, LNCaP cells were also able to decrease the proliferation of cocultured osteoblastic cells. In contrast, the increased expression of Cx43 in PC-3 cells led to an unfunctional, cytoplasmic localization of the protein and was correlated with a reduction of proliferation, adhesion and invasion of the cells. In conclusion, the localization and the functionality of Cx43 may govern the ability of PCa cells to metastasize in bones. PMID- 22080400 TI - Improvement in academic behaviors after successful treatment of convergence insufficiency. AB - PURPOSE: To determine whether treatment of symptomatic convergence insufficiency (CI) has an effect on Academic Behavior Survey (ABS) scores. METHODS: The ABS is a six-item survey developed by the Convergence Insufficiency Treatment Trial Group that quantifies the frequency of adverse school behaviors and parental concern about school performance on an ordinal scale from 0 (never) to 4 (always) with total scores ranging from 0 to 24. The ABS was administered at baseline and after 12 weeks of treatment to the parents of 218 children aged 9 to 17 years with symptomatic CI, who were enrolled in the Convergence Insufficiency Treatment Trial and randomized into (1) home-based pencil push-ups; (2) home-based computer vergence/accommodative therapy and pencil push-ups; (3) office-based vergence/accommodative therapy with home reinforcement; and (4) office-based placebo therapy with home reinforcement. Participants were classified as successful (n = 42), improved (n = 60), or non-responder (n = 116) at the completion of 12 weeks of treatment using a composite measure of the symptom score, nearpoint of convergence, and positive fusional vergence. Analysis of covariance methods were used to compare the mean change in ABS between response to treatment groups while controlling for the ABS score at baseline. RESULTS: The mean ABS score for the entire group at baseline was 12.85 (SD = 6.3). The mean ABS score decreased (improved) in those categorized as successful, improved, and non-responder by 4.0, 2.9, and 1.3 points, respectively. The improvement in the ABS score was significantly related to treatment outcome (p < 0.0001), with the ABS score being significantly lower (better) for children who were successful or improved after treatment as compared to children who were non-responders (p = 0.002 and 0.043, respectively). CONCLUSIONS: A successful or improved outcome after CI treatment was associated with a reduction in the frequency of adverse academic behaviors and parental concern associated with reading and school work as reported by parents. PMID- 22080402 TI - A novel D-ring modified taxoid: synthesis and biological evaluation of a gamma lactone analogue of docetaxel. AB - The synthesis of a novel D-ring modified docetaxel analogue, in which the oxetane ring is replaced with a gamma-lactone, was achieved from 10-deacetylbaccatin III. The key steps of the synthesis include the direct acetylation of the secondary hydroxyl group at C-5 and D-ring opening and intramolecular aldol reaction to form the gamma-lactone. In MTT assays, this analogue proved to have equipotent cytotoxicity relative to paclitaxel towards HCT8, HePG2 and BGC23 cancer cell lines, and be more potent than paclitaxel against A549 and A375. It represents the first example of D-ring modified taxoids with significant cytotoxicity. PMID- 22080403 TI - Promoted hydrogen release from ammonia borane with mannitol via a solid-state reaction route. AB - Promoted hydrogen release from ammonia borane (NH(3)BH(3), AB) with mannitol (C(6)H(8)(OH)(6), MA) additive is reported. It is found that for the MA/2AB sample, the dehydrogenation temperature is lowered by ~25 degrees C compared to that of neat AB, the liberation of undesired byproduct borazine is suppressed, and the released ammonia can be removed by using anhydrous MgCl(2) as absorber. The analyses of Raman, Fourier transform infrared spectroscopy and (11)B nuclear magnetic resonance spectroscopy demonstrate the breaking of B-N, B-H and O-H bonds and the formation of B-O bonds for the dehydrogenation process of MA/2AB. These results suggest a solid-state dehydrogenation reaction between AB and MA: the B-H(delta-) bonds in AB and the O-H(delta+) bonds in MA combine with each other to release H(2). Furthermore, the use of the perfect -OH carrier MA as additive leads to a straightforward understanding of the improved dehydrogenation of AB under the effect of hydroxyl groups in the solid state. PMID- 22080404 TI - Enhanced cytotoxicity and decreased CD8 dependence of human cancer-specific cytotoxic T lymphocytes after vaccination with low peptide dose. AB - In mice, vaccination with high peptide doses generates higher frequencies of specific CD8+ T cells, but with lower avidity compared to vaccination with lower peptide doses. To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant. Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups. Also, CD8+ T cell differentiation and cytokine production ex vivo were similar in the two groups. Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo. In accordance, CD8+ T cell clones derived from low peptide dose-vaccinated patients showed significantly increased degranulation and stronger cytotoxicity. In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers. Furthermore, CD8+ T cell clones from low peptide dose-vaccinated patients bound CD8 binding-deficient tetramers more efficiently, suggesting that they may express higher affinity TCRs. We conclude that low peptide dose vaccination generated CD8+ T cell responses with stronger cytotoxicity and lower CD8 dependence. PMID- 22080405 TI - Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines. AB - Myeloid-derived suppressor cells (MDSC) are important regulators of the immune system and key players in tumor-induced suppression of T-cell responses. CD14+HLA DR-/low MDSC have been detected in a great number of malignancies, including melanoma. MDSC are known to be impaired in their ability to differentiate along the myeloid lineage, e.g., into dendritic cells (DC). This is a concern for utilization of monocyte-derived DC for vaccination of patients with melanoma or other cancers exhibiting accumulation of CD14+ MDSC. When producing DC according to standard operating procedures of two currently ongoing clinical trials, we found that MDSC co-purified with monocytes isolated by elutriation. MDSC frequencies did not affect yield or viability of the produced DC, but induced a dose-dependent decrease in DC maturation, ability to take up antigen, migrate and induce T-cell IFNgamma production. Changes in DC characteristics were most notable when 'pathological' frequencies of >50% CD14+HLA-DR- cells were present in the starting culture. The impaired DC quality could not be explained by altered cytokine production or increased oxidative stress in the cultures. Tracking of HLA-DR- cells throughout the culture period revealed that the observed changes were partially due to the impaired maturation and functionality of the originally HLA-DR- population, but also to their negative effects on HLA DR+ cells. In conclusion, MDSC could be induced to differentiate into DC but, due to the impairment of overall DC vaccine quality when >50% HLA-DR- cells were present in the starting culture, their removal could be advisable. PMID- 22080408 TI - Immunological monitoring of the tumor immunoenvironment for clinical trials. AB - Monitoring of immunotherapeutic clinical trials has undergone a considerable change in the last decade resulting in a general agreement that immune monitoring should guide the development of cancer vaccines. The emphasis on immune cell functions and quantitation of antigen-specific T cells have been playing a major role in the attempts to establish meaningful correlations between therapy-induced alterations in immune responses and clinical endpoints. However, one significant unresolved issue in modern immunotherapy is that when a tumor-specific cellular immune response is observed following the course of immunotherapy, it does not always lead to clinically proven cancer regression. This disappointing lack of a correlation between the tumor-specific cytotoxic immune responses and the clinical efficacy of immunotherapy may be explained, among other reasons, by the notion that the analysis of any single immunological parameter is not sufficient to provide clinically feasible information about the complex interactions between different cell subsets in the peripheral blood and immune, tumor, and stromal cells in the tumor milieu. By contrast, a systemic approach is required for improving the quality of a serial monitoring to ensure that it adequately and reliably measures potential changes induced in patients by administered vaccines or immunomodulators. Comprehensive evaluation of the balance between the immunostimulatory and immunosuppressive compartments of the immune system could be critical for a better understanding of how a given immunotherapy works or does not work in a particular clinical trial. New approaches to characterize tumor infiltrating leukocytes, their phenotypic, biochemical, and genetic characteristics within the tumor microenvironment need to be developed and validated and should complement current monitoring techniques. These immune monitoring assays for the local tumor immunoenvironment should be developed, validated, and standardized for reliability and consistency in order to establish the overall performance standards. PMID- 22080409 TI - The palladium-catalyzed desulfitative cyanation of arenesulfonyl chlorides and sodium sulfinates. AB - A palladium-catalyzed desulfitative cyanation of arenesulfonyl chlorides and sodium sulfinates has been developed, providing aryl nitriles in moderate to excellent yields. It represents a facile procedure to access aryl nitriles. PMID- 22080411 TI - Streptomyces deserti sp. nov., isolated from hyper-arid Atacama Desert soil. AB - The taxonomic position of a Streptomyces strain isolated from a hyper-arid desert soil was established using a polyphasic approach. The organism had chemical and morphological properties typical of the genus Streptomyces and formed a phyletic line at the periphery of the Streptomyces coeruleorubidus subcluster in the 16S rRNA gene tree. DNA:DNA relatedness values between the isolate and its nearest phylogenetic neighbours, Streptomyces lomondensis NRRL 3252(T) and Streptomyces lusitanus NRRL B-12501(T) were 42.5 (+/-0.48)% and 25.0 (+/-1.78)%, respectively. The isolate was readily distinguished from these organisms using a combination of morphological and phenotypic properties. On the basis of these results, it is proposed that isolate C63(T) (CGMCC 4.6997(T), = KACC 15425(T)) be classified as the type strain of Streptomyces deserti sp. nov. PMID- 22080410 TI - Real-world experience of drug-eluting stents in saphenous vein grafts compared to native coronary arteries: results from the prospective multicenter German DES.DE registry. AB - BACKGROUND: Bypass-graft intervention was associated with worse outcomes in the bare-metal stent era. Without sufficiently powered data from subgroup analyses, and in absence of randomized controlled trials targeting clinical endpoints, controversy is ongoing over safety and efficacy of drug-eluting stents (DES) in saphenous vein graft (SVG) lesions. METHODS AND RESULTS: Between October 2005 and October 2006, 5,183 patients receiving DES in SVG (n = 251) or native coronary arteries (NCA) (n = 4,932) were enrolled at 98 DES.DE sites. The composite of death, myocardial infarction (MI), and stroke defined as major adverse cardiac and cerebrovascular events (MACCE) and target-vessel revascularization (TVR) were defined as primary endpoints. Baseline clinical and descriptive morphology of coronary artery disease revealed more severe lesions and comorbidities in the SVG group. At 1-year follow-up, the SVG group suffered from higher rates of overall death (6.6 vs. 2.5%; p < 0.0001), myocardial infarction (5.9 vs. 2.2%; p < 0.0001), MACCE (13.6 vs. 5.4%; p < 0.0001), TVR (17.7 vs. 10.4%; p < 0.001) and overall stent thrombosis (10.0 vs. 3.7%; p < 0.0001). CONCLUSION: Data collected in DES.DE revealed that first generation DES used in SVG lesions did not offset the worse clinical outcomes of bypass-graft intervention. Such sobering results in SVG may suggest to opt for native vessel PCI preferentially or occasionally for surgical reintervention as decided by the Heart Team. PMID- 22080412 TI - The BISMiS 2011 special issue on prokaryotic systematics, a vital discipline entering a period of transition. PMID- 22080413 TI - Natural and artificial ion channels for biosensing platforms. AB - The single-molecule selectivity and specificity of the binding process together with the expected intrinsic gain factor obtained when utilizing flow through a channel have attracted the attention of analytical chemists for two decades. Sensitive and selective ion channel biosensors for high-throughput screening are having an increasing impact on modern medical care, drug screening, environmental monitoring, food safety, and biowarefare control. Even virus antigens can be detected by ion channel biosensors. The study of ion channels and other transmembrane proteins is expected to lead to the development of new medications and therapies for a wide range of illnesses. From the first attempts to use membrane proteins as the receptive part of a sensor, ion channels have been engineered as chemical sensors. Several other types of peptidic or nonpeptidic channels have been investigated. Various gating mechanisms have been implemented in their pores. Three technical problems had to be solved to achieve practical biosensors based on ion channels: the fabrication of stable lipid bilayer membranes, the incorporation of a receptor into such a structure, and the marriage of the modified membrane to a transducer. The current status of these three areas of research, together with typical applications of ion-channel biosensors, are discussed in this review. PMID- 22080415 TI - A general route to synthesize water-dispersive noble metal-iron oxide bifunctional hybrid nanoparticles. AB - This communication describes a simple, general route for preparing bifunctional hybrid nanoparticles based on direct adsorption and spontaneous reduction of Ag(+) and Pd(2+) onto the surface of carbon-encapsulated superparamagnetic colloidal nanoclusters. Because of the existence of carbon coating and surface hydrophilic carboxyl, the bifunctional hybrid nanoparticles show excellent water dispersity. In addition, the size (35 nm-86 nm) and number of Ag nanocrystals can be tuned by changing the molar ratios and reaction concentration between Ag(+) and nanoclusters. PMID- 22080416 TI - An evaluation of three processing methods and the effect of reduced culture times for faster direct identification of pathogens from BacT/ALERT blood cultures by MALDI-TOF MS. AB - Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) is a fast and reliable method for the identification of bacteria from agar media. Direct identification from positive blood cultures should decrease the time to obtaining the result. In this study, three different processing methods for the rapid direct identification of bacteria from positive blood culture bottles were compared. In total, 101 positive aerobe BacT/ALERT bottles were included in this study. Aliquots from all bottles were used for three bacterial processing methods, i.e. the commercially available Bruker's MALDI Sepsityper kit, the commercially available Molzym's MolYsis Basic5 kit and a centrifugation/washing method. In addition, the best method was used to evaluate the possibility of MALDI application after a reduced incubation time of 7 h of Staphylococcus aureus- and Escherichia coli-spiked (1,000, 100 and 10 colony-forming units [CFU]) aerobe BacT/ALERT blood cultures. Sixty-six (65%), 51 (50.5%) and 79 (78%) bottles were identified correctly at the species level when the centrifugation/washing method, MolYsis Basic 5 and Sepsityper were used, respectively. Incorrect identification was obtained in 35 (35%), 50 (49.5%) and 22 (22%) bottles, respectively. Gram-positive cocci were correctly identified in 33/52 (64%) of the cases. However, Gram-negative rods showed a correct identification in 45/47 (96%) of all bottles when the Sepsityper kit was used. Seven hours of pre-incubation of S. aureus- and E. coli-spiked aerobe BacT/ALERT blood cultures never resulted in reliable identification with MALDI-TOF MS. Sepsityper is superior for the direct identification of microorganisms from aerobe BacT/ALERT bottles. Gram-negative pathogens show better results compared to Gram-positive bacteria. Reduced incubation followed by MALDI-TOF MS did not result in faster reliable identification. PMID- 22080417 TI - Impact of Helicobacter pylori infection and microscopic duodenal histopathological changes on clinical symptoms of patients with functional dyspepsia. AB - AIM: To evaluate the microscopic histopathological changes in duodenal tissue and its relationship to the severity of symptoms in patients with functional dyspepsia while taking the effect of Helicobacter pylori (H. pylori) infection into account. METHODS: Several gastric and duodenal biopsy specimens were obtained in 217 patients with functional dyspepsia and were evaluated for H. pylori infection and histopathological changes. Severity of symptoms was assessed by Leeds Dyspepsia Questionnaire (LDQ) and its relationship to histopathological changes and H. pylori infection status was assessed. RESULTS: Helicobacter pylori infection was associated with presence and severity of microscopic duodenitis (p < 0.001). In H. pylori-infected patients, the presence of microscopic duodenitis was independent of microscopic gastritis (p = 0.74). Severity of dyspepsia symptoms was not higher in H. pylori-infected patients than non-infected patients (p = 0.15), but in the presence of H. pylori infection and microscopic gastritis, microscopic duodenitis significantly worsened the LDQ symptom severity score (p < 0.001). In multivariate analysis, the odds of experiencing severe symptoms in patients with severe microscopic duodenitis was 2.22 times greater than in individuals with very mild, mild, or moderate duodenitis. CONCLUSIONS: Microscopic duodenitis in H. pylori-infected patients may play a major role in producing and aggravating symptoms in FD patients and may be a determinant factor to consider in whether to treat H. pylori infection in functional dyspepsia. PMID- 22080418 TI - Incidental pancreatography via ERCP in patients with anomalous pancreaticobiliary junction does not result in pancreatitis in a North American population. AB - INTRODUCTION: Anomalous pancreaticobiliary junction (APBJ) is the term used to describe anatomical variants of pancreatic and biliary ductal junctional anatomy. Patients have junction of the pancreatic and bile ducts located outside the duodenal wall, forming a long common channel. We report our findings and clinical outcomes in a North American series of patients with APBJ undergoing ERCP. METHODS: Retrospective chart review. RESULTS: We reviewed 2,218 ERCP performed on 1,050 patients. Twelve patients (1.1%) with APBJ were identified (5F, 7M). No patient had an associated choledochocele. Mean age was 53.2 (range 17-85). A total of 43 ERCP procedures were performed on these 12 patients. All patients experienced passive pancreatography. No patient developed post-ERCP pancreatitis. Only one patient had a history of antecedent pancreatitis. CONCLUSIONS: In North American patients undergoing ERCP, 1.1% of patients had APBJ. Our study population was predominately Caucasian, male, and in all but one patient lacked a history of prior pancreatitis. No patient developed post-ERCP pancreatitis. This suggests that APBJ may have different clinical manifestations in a North American population when compared to Asian populations. PMID- 22080419 TI - [Is the determination of the defibrillation threshold in patients with an implantable cardioverter-defibrillator still required?]. AB - BACKGROUND: Intraoperative testing of implantable cardioverter-defibrillators (ICDs) is time consuming and associated with risks. In the present study, we elucidated whether the initial implantation of an ICD with high energy output makes intraoperative defibrillation threshold testing (DFTT) unnecessary even though antiarrhythmic (AA) therapy is needed in the future. METHODS: A total of 111 patients (94 men, 17 women) receiving an ICD with subsequent AA therapy (mexiletine, amiodarone, sotalol, flecainide) were analyzed retrospectively. DFT was performed during ICD implantation and after AA drug therapy. In a second step, DFT results from the study cohort were analyzed for implantation of virtual ICDs with either low (<= 30 J, LOD), intermediate (34 J, IOD), or high energy output (36 J, HOD). RESULTS: In the study cohort, all patients reached the safety margin (SM) of 10 J between DFT and maximal shock energy of the ICD. After loading of AA agents, 6 patients (12%) with a LOD, 3 patients (11%) with an IOD, and 3 (13%) patients with a HOD failed the 10 J SM. Using virtual ICDs, 6 (5.5%) patients with a LOD, 1 patient (1%) with an IOD, and no patients with a HOD would have failed the 10 J SM. After loading of AA agents, 18 patients (16%) with a virtual LOD, 12 patients (10.8%) with an IOD, and still 9 patients (8%) with a HOD would have failed the 10 J SM. CONCLUSION: Our results demonstrate that the 10 J SM would have been achieved intraoperatively in all patients with virtual HOD ICDs. Thus, determination of the DFT during implantation does not seem to be obligatory. However, in patients receiving AA agents, DFT testing is still required. PMID- 22080420 TI - Effect of carbon nanotube functionalization in micro-solid-phase extraction (MU SPE) integrated into the needle of a syringe. AB - In this paper, we report the implementation of polar and nonpolar functionalized multiwalled carbon nanotubes (MWCNTs) as sorbent in MU-SPE integrated into the needle of a syringe. Excellent preconcentration of diverse pharmaceutical analytes was possible without the need for specific pH adjustments using just 300 MUg of functionalized nanotubes. Enrichment factors were as high as 6.4, extraction efficiencies were as high as 25.6%, and detection limits as low as 0.08 ng/ml were obtained. The sorption on nanotubes followed Freundlich isotherms, and it was seen that polar analytes adsorbed more strongly on carboxylated MWCNTs, while amphoteric, relatively less polar and basic analytes had greater affinity for MWCNT and those with octadecylamine functionalization. PMID- 22080422 TI - Chronotherapy in hypertension: a pill at night makes things right? PMID- 22080421 TI - Comparative proteomic analysis of grain development in two spring wheat varieties under drought stress. AB - Two spring wheat varieties Ningchun 4 and Chinese Spring with good and poor resistance to abiotic stress, respectively, were used to investigate proteomic changes in the developing grains under drought stress by a comparative proteomics approach. A total of 152 protein spots showed at least twofold differences in abundance on two-dimensional electrophoresis (2-DE) maps, of which 28 and 68 protein spots were identified by MALDI-TOF and MALDI-TOF/TOF mass spectrometry, respectively. Of the 96 identified protein spots, six different expression patterns were found and they were involved in stress/defense/detoxification, carbohydrate metabolism, photosynthesis, nitrogen metabolism, storage proteins and some other important functions. Comparative proteomic analysis revealed that under the drought conditions the decreased degree of ascorbate peroxidases was more significant in Chinese Spring than in Ningchun 4 during grain development whereas translationally controlled tumor protein, which was significantly upregulated at 14 DAF, was present in Ningchun 4 and absent in Chinese Spring. The Rubisco large subunit displayed an upregulated expression pattern in Ningchun 4. In addition, two drought-tolerant proteins, triosephosphate isomerase and oxygen-evolving complex showed B and F type expression patterns in Chinese Spring, but D and B types in Ningchun 4, respectively. These differentially expressed proteins might be responsible for the stronger drought resistance of Ningchun 4 compared to Chinese Spring. PMID- 22080423 TI - Tagged fibrocystin sheds its secrets. PMID- 22080424 TI - The altered expression of alpha1 and beta3 subunits of the gamma-aminobutyric acid A receptor is related to the hepatitis C virus infection. AB - The modulation of the gamma-aminobutyric acid type A (GABA A) receptors activity was observed in several chronic hepatitis failures, including hepatitis C. The expression of GABA A receptor subunits alpha1 and beta3 was detected in peripheral blood mononuclear cells (PBMCs) originated from healthy donors. The aim of the study was to evaluate if GABA A alpha1 and beta3 expression can also be observed in PBMCs from chronic hepatitis C (CHC) patients and to evaluate a possible association between their expression and the course of hepatitis C virus (HCV) infection. GABA A alpha1- and beta3-specific mRNAs presence and a protein expression in PBMCs from healthy donors and CHC patients were screened by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. In patients, HCV RNA was determined in sera and PBMCs. It was shown that GABA A alpha1 and beta3 expression was significantly different in PBMCs from CHC patients and healthy donors. In comparison to healthy donors, CHC patients were found to present an increase in the expression of GABA A alpha1 subunit and a decrease in the expression of beta3 subunit in their PBMCs. The modulation of alpha1 and beta3 GABA A receptors subunits expression in PBMCs may be associated with ongoing or past HCV infection. PMID- 22080425 TI - Signs and symptoms predicting influenza in children: a matched case-control analysis of prospectively collected clinical data. AB - We aimed to determine whether there are signs or symptoms that could help clinicians to distinguish between influenza and other respiratory infections. The clinical data for this matched case-control analysis were derived from a 2-year prospective cohort study of respiratory infections among children aged<=13 years. At any signs of respiratory infection, the children were examined and nasal swabs were obtained for virologic analyses. Cases were 353 children with laboratory confirmed influenza and controls were 353 children with respiratory symptoms who tested negative for influenza. Cases and controls were matched for gender, age, and timing of the visit. In the multivariate conditional logistic regression analyses, fever was the only sign that independently predicted influenza virus infection, with odds ratios ranging from 13.55 (95% confidence interval [CI], 6.90-26.63) to 50.10 (95% CI, 16.25-154.45), depending on the degree of fever. In all analyses, the predictive capability of fever increased with incremental elevations in the child's temperature. The likelihood ratio of fever>=40.0 degrees C in predicting influenza was 6.00 (95% CI, 2.80-12.96). Among unselected children seen as outpatients during influenza outbreaks, fever is the only reliable predictor of influenza virus infection. The optimal use of influenza specific antiviral drugs in children may require virologic confirmation. PMID- 22080426 TI - An end-users oriented methodology for enhancing the integration of knowledge on soil-water-sediment systems in River Basin Management: an illustration from the AquaTerra project. AB - Research results in environmental and socio-economic sciences are often under used by stakeholders involved in the management of natural resources. To minimise this gap, the FP6 EU interdisciplinary project AquaTerra (AT) developed an end users' integration methodology in order to ensure that the data, knowledge and tools related to the soil-water-sediment system that were generated by the project were delivered in a meaningful way for end-users, thus improving their uptake. The methodology and examples of its application are presented in this paper. From the 408 project deliverables, 96 key findings were identified, 53 related to data and knowledge, and 43 describing advanced tools. River Basin Management (RBM) stakeholders workshops identified 8 main RBM issues and 25 specific stakeholders' questions related to RBM which were classified into seven groups of cross-cutting issues, namely scale, climate change, non-climatic change, the need for systemic approaches, communication and participation, international and inter-basin coordination and collaboration, and the implementation of the Water Framework Directive. The integration methodology enabled an assessment of how AT key findings meet stakeholders' demands, and for each main RBM issue and for each specific question, described the added-value of the AT project in terms of knowledge and tools generated, key parameters to consider, and recommendations that can be made to stakeholders and the wider scientific community. Added value and limitations of the integration methodology and its outcomes are discussed and recommendations are provided to further improve integration methodology and bridge the gaps between scientific research data and their potential uptake by end-users. PMID- 22080427 TI - Local residents perception of benefits and losses from protected areas in India and Nepal. AB - High densities of people living around protected areas (PAs) in South Asia require management strategies to balance conservation goals and livelihood needs. Based on a survey of 777 households around five PAs in India and Nepal, this paper provides a comparative perspective of Indian and Nepali households' views of protected area benefits and costs, their attitude toward conservation in general, and attitude toward protected area staff. Results indicate mixed responses towards tourism, varying from very favorable in Nepal to less favorable in India. The majority (81%) held positive attitudes towards the existence and importance of PAs but had negative perceptions of PA staff (69%). Most residents perceived benefits from access to fuel wood, fodder and other PA resources including benefits from tourism, while crop and livestock losses from wildlife were the main costs. Households overall positive attitudes towards the PAs and conservation despite high losses from living around PAs suggests that local residents may support conservation if their livelihood needs are met. Comparisons of household attitudes and perceptions suggest that locally based strategies rather than top-down approaches are likely to be more effective. Extending PA benefits to smaller landholders, households that are highly resource-dependent or experiencing higher income losses from human-wildlife conflicts, and less educated residents are particularly important to balance costs and losses from living around protected areas. PMID- 22080428 TI - Assessing watershed transport of atrazine and nitrate to evaluate conservation practice effects and advise future monitoring strategies. AB - Continued public support for U.S. taxpayer funded programs aimed at reducing agricultural pollutants depends on clear demonstrations of water quality improvements. The objective of this research was to determine if implementation of agricultural best management practices (BMPs) in the Goodwater Creek Experimental Watershed (GCEW) resulted in changes to atrazine and nitrate (NO(3) N) loads during storm events. An additional objective was to estimate future monitoring periods necessary to detect a 5, 10, 20, and 25% reduction in atrazine and NO(3)-N event load. The GCEW is a 73 km(2) watershed located in northcentral Missouri, USA. Linear regressions and Akaike Information Criteria were used to determine if reductions in atrazine and NO(3)-N event loads occurred as BMPs were implemented. No effects due to any BMP type were indicated for the period of record. Further investigation of event sampling from the long-term GCEW monitoring program indicated errors in atrazine load calculations may be possible due to pre-existing minimum threshold levels used to trigger autosampling and sample compositing. Variation of event loads was better explained by linear regressions for NO(3)-N than for atrazine. Decommissioning of upstream monitoring stations during the study period represented a missed opportunity to further explain variation of event loads at the watershed outlet. Atrazine requires approximately twice the monitoring period relative to NO(3)-N to detect future reductions in event load. Appropriate matching of pollutant transport mechanisms with autosampling protocols remains a critical information need when setting up or adapting watershed monitoring networks aimed at detecting watershed-scale BMP effects. PMID- 22080429 TI - Phyllosphere bacterial communities of trichome-bearing and trichomeless Arabidopsis thaliana leaves. AB - This study aimed to investigate whether the presence of trichomes as conspicuous physical attributes of the leaf surface affects the microbial community composition on Arabidopsis thaliana leaves. The A. thaliana ecotype Col-0 and its trichomeless gl1 mutant were grown in growth cabinets under climate-controlled conditions. The gl1 mutant showed a similar wax composition as the Col-0 wild type with slightly reduced amounts of C(29), C(31) and C(33) alkanes by GC/MS and GC/FID analyses. 120 bacterial isolates representing 39 bacterial genera were obtained from A. thaliana Col-0 leaf surfaces. Phylogenetic analysis of nearly full-length 16S rRNA sequences from 29 selected isolates confirmed their affiliation to the Proteobacteria (Alpha-, Beta-, Gamma-), Actinobacteria, Bacteroidetes and Firmicutes. The bacterial diversity on A. thaliana ecotype Col 0 and its gl1 mutant, devoid of trichomes, were further compared by denaturing gradient gel electrophoresis (DGGE). Banding patterns and sequencing of representative DGGE bands revealed the presence of phylotypes related to Sphingomonas (Alphaproteobacteria), Methylophilus (Betaproteobacteria) and Dyadobacter (Bacteroidetes) which are common phyllosphere inhabitants. Furthermore, wildtype and trichomeless mutant plants were exposed to outdoor conditions for 4-5 weeks. The DGGE gels showed only minor differences between the two plant lines, thus suggesting that trichomes per se do not affect bacterial diversity on Arabidopsis leaves under the experimental conditions tested. PMID- 22080430 TI - Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination. AB - PURPOSE: Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested utility in combining it with an HDAC inhibitor such as vorinostat. Thus, in this study in vitro studies assessed the potential utility of combining marizomib and vorinostat, followed by a clinical trial with the objectives of assessing the recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), safety and preliminary anti-tumor activity of the combination in patients. EXPERIMENTAL DESIGN: Combinations of marizomib and vorinostat were assessed in vitro. Subsequently, in a Phase 1 clinical trial patients with melanoma, pancreatic carcinoma or Non-small Cell Lung Cancer (NSCLC) were given escalating doses of weekly marizomib in combination with vorinostat 300 mg daily for 16 days in 28 day cycles. In addition to standard safety studies, proteasome inhibition and pharmacokinetics were assayed. RESULTS: Marked synergy of marizomib and vorinostat was seen in tumor cell lines derived from patients with NSCLC, melanoma and pancreatic carcinoma. In the clinical trial, 22 patients were enrolled. Increased toxicity was not seen with the combination. Co-administration did not appear to affect the PK or PD of either drug in comparison to historical data. Although no responses were demonstrated using RECIST criteria, 61% of evaluable patients demonstrated stable disease with 39% having decreases in tumor measurements. CONCLUSIONS: Treatment of multiple tumor cell lines with marizomib and vorinostat resulted in a highly synergistic antitumor activity. The combination of full dose marizomib with vorinostat is tolerable in patients with safety findings consistent with either drug alone. PMID- 22080431 TI - A novel LED-based device for occlusal caries detection. AB - The aim of this in-vitro study was to compare the performance of laser-based (DIAGNOdent, KaVo, Biberach, Germany) and LED-based (Midwest Caries I.D., DENTSPLY Professional, New York, USA) caries detectors in the detection of occlusal caries in permanent molars. The study consisted of 129 visually sound or non-cavitated pits or fissures in 82 extracted permanent human molar teeth. Two trained examiners used the laser-based and LED-based caries detectors to examine the fissures for caries. The teeth were then sectioned at the surfaces suspected of containing occlusal caries and histologically evaluated using stereomicroscopy as a gold standard. Inter-examiner reliability of the caries detector examination was assessed using Cohen's Kappa statistics. The sensitivity, specificity, and accuracy in diagnosing occlusal caries using the two devices were calculated according to appropriate cut-off scores. Receiver operating characteristic (ROC) curves were also determined to compare the diagnostic performance of the devices in occlusal caries diagnosis. The cut-off level of significance was taken as p = 0.005. Cohen's Kappa showed substantial agreement for the laser-based caries detector (0.74), and almost perfect agreement for the LED-based (0.89) caries detector. The specificity of the laser-based device varied from 0.49 to 0.97 at T1 and T2. Its sensitivity varied from 0.33 to 0.65 at T1 and T2. The specificity of the LED-based device varied from 0.48 to 0.56 at T1 and T2. Its sensitivity varied from 0.65 to 0.84 at T1 and from 0.80 to 0.84 at T2. Taking the limitations of the current study into consideration, the DIAGNOdent laser pen was more accurate in determining when teeth were free of occlusal caries than was the Midwest Caries I.D. LED-based device, although the Midwest Caries I.D. device more often revealed the presence of occlusal caries than did the DIAGNOdent pen. PMID- 22080432 TI - Reference genes for qPCR assays in toxic metal and salinity stress in two flatworm model organisms. AB - The flatworm species Schmidtea mediterranea and Macrostomum lignano have become new and innovative model organisms in stem cell, regeneration and tissue homeostasis research. Because of their unique stem cell system, (lab) technical advantages and their phylogenetic position within the Metazoa, they are also ideal candidate model organisms for toxicity assays. As stress and biomarker screenings are often performed at the transcriptional level, the aim of this study was to establish a set of reference genes for qPCR experiments for these two model organisms in different stress situations. We examined the transcriptional stability of nine potential reference genes (actb, tubb, ck2, cox4, cys, rpl13, gapdh, gm2ap, plscr1) to assess those that are most stable during altered stress conditions (exposure to carcinogenic metals and salinity stress). The gene expression stability was evaluated by means of geNorm and NormFinder algorithms. Sets of best reference genes in these analyses varied between different stress situations, although gm2ap and actb were stably transcribed during all tested combinations. In order to demonstrate the impact of bad normalisation, the stress-specific gene hsp90 was normalised to different sets of reference genes. In contrast to the normalisation according to GeNorm and NormFinder, normalisation of hsp90 in Macrostomum lignano during cadmium stress did not show a significant difference when normalised to only gapdh. On the other hand an increase of variability was noticed when normalised to all nine tested reference genes together. Testing appropriate reference genes is therefore strongly advisable in every new experimental condition. PMID- 22080433 TI - DNA damage in cichlids from an oil production facility in Guatemala. AB - This study focused on several wetlands in Laguna del Tigre National Park (Guatemala) as part of Conservation International's Rapid Assessment Program. Sediment and water samples were collected from a laguna near Xan field, Guatemala's largest oil facility, and three other sites for determination of levels of polycyclic aromatic hydrocarbons (PAHs). Cichlid fish (Thorichthys meeki and Vieja synspila) were collected for determination of DNA strand breakage (by gel electrophoresis), chromosomal breakage (flow cytometry), and fin erosion. For T. meeki from Xan field, chromosomal breakage and strand breakage was greater than in at least two of the three reference sites. For V. synspila, chromosomal breakage and strand breakage were greater in Xan than one of the two reference sites. Fin erosion was observed only at the Xan laguna. Genetic biomarker effects and fin erosion, along with patterns of aqueous PAH concentrations, indicate that fish are affected by anthropogenic contaminants. PAHs were elevated at some reference sites, but environmental forensic analysis suggested a pyrogenic or diagenic origin. It is possible that oil field brines injected into the ground water caused fin erosion and genotoxicity in fish at Xan field, and it is also possible that pyrogenic PAHs influence levels of DNA damage in reference sites. These analyses represent one of the first efforts to examine genotoxicity in native Mesoamerican cichlids. PMID- 22080435 TI - Computer animated relaxation therapy in children between 7 and 13 years with tension-type headache: a pilot study. AB - This pilot study evaluated the effect of computer animated relaxation therapy in children between 7 and 13 years with tension-type headache and the children's experiences with the therapy. The therapy consisted of an uncontrolled nine session course in modified progressive relaxation therapy assisted by computer animated surface EMG provided from the trapezius muscles and with the physiotherapist as a participant observer. Outcome measures were (a) headache frequency and intensity, (b) pericranial tenderness, (c) tension patterns, and (d) evaluations assessed at baseline and at 3 months follow up. Nine children, mean age 10.9 (SD 1.7) years, diagnosed with frequent episodic or chronic tension type headache completed the course. The results showed a mean improvement of 45% for headache frequency at 3 months follow up versus baseline and a significant reduction in headache frequency for all participants and in Total Tenderness Score for children with frequent episodic tension-type headache. The children expressed a growing understanding of body reactions and an acquired ability to deactivate and regulate these reactions. Computer animated SEMG seems an applicable learning strategy for young headache sufferers. This study suggests that children below the age of 13 need both the dialog and guidance from a participant observer in order to achieve body awareness. PMID- 22080434 TI - Organic carbon source in formulated sediments influences life traits and gene expression of Caenorhabditis elegans. AB - River water quality is strongly influenced by their sediments and their associated pollutants. To assess the toxic potential of sediments, sediment toxicity tests require reliable control sediments, potentially including formulated control sediments as one major option. Although some standardization has been carried out, one critical issue still remains the quality of sediment organic matter (SOM). Organic carbon not only binds hydrophobic contaminants, but may be a source of mild toxicity, even if the SOM is essentially uncontaminated. We tested two different sources of organic carbon and the mixture of both (Sphagnum peat (P) and one commercial humic substances preparation HuminFeed((r)), HF) in terms of life trait variables and expression profiles of selected life performance and stress genes of the nematode Caenorhabditis elegans. In synchronous cultures, gene expression profiling was done after 6 and 48 h, respectively. The uncontaminated Sphagnum P reduced growth, but increased numbers of offspring, whereas HF did not significantly alter life trait variables. The 6 h expression profile showed most of the studied stress genes repressed, except for slight to strong induction in cyp-35B1 (all exposures), gst 38 (only mixture), and small hsp-16 genes (all exposures). After 48 h, the expression of almost all studied genes increased, particularly genes coding for antioxidative defense, multiple xenobiotic resistance, vitellogenin-like proteins, and genes regulating lifespan. Overall, even essentially uncontaminated SOM may induce several modes of action on the molecular level in C. elegans which may lead to false results if testing synthetic xenobiotics. This contribution is a plea for a strict standardization of the SOM quality in formulated sediments and to check for corresponding effects in other model sediment organisms, especially if using molecular toxicity endpoints. PMID- 22080436 TI - Empirical evidence of the effectiveness of concept mapping as a learning intervention for nuclear medicine technology students in a distance learning radiation protection and biology course. AB - Metacognitive learning strategies are based on instructional learning theory, which promotes deep, meaningful learning. Educators in a baccalaureate-level nuclear medicine technology program demonstrated that students enrolled in an online, distance learning section of an introductory radiation protection and radiobiology course performed better when traditional instruction was supplemented with nontraditional metacognitive learning strategies. METHODS: The metacognitive learning strategy that was used is best known as concept mapping. The concept map, in addition to the standard homework problem assignment and opportunity for question-answer sessions, became the template for misconception identification and remediation interactions between the instructor and the student. The control group relied on traditional homework problems and question answer sessions alone. Because students in both the "treatment" groups (i.e., students who used concept mapping) and the control group were distance learning students, all personal communications were conducted via e-mail or telephone. The final examination of the course was used to facilitate a quantitative comparison of the performance of students who used concept mapping and the performance of students who did not use concept mapping. RESULTS: The results demonstrated a significantly higher median final examination score for the concept mapping group than for the non-concept mapping group (z = -2.0381, P = 0.0415), with an appropriately large effect size (2.65). CONCLUSION: Concept mapping is a cognitive learning intervention that effectively enables meaningful learning and is suitable for use in the independent learner-oriented distance learning environments used by some nuclear medicine technology programs. PMID- 22080437 TI - Effect of asiaticoside on 99mTc-tetrofosmin and 99mTc-sestamibi uptake in MCF-7 cells. AB - This study was done to examine the effect of asiaticoside on MCF-7 cell uptake of (99m)Tc-tetrofosmin ((99m)Tc-Tfos) and (99m)Tc-sestamibi ((99m)Tc-MIBI). METHODS: The 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the effect of a 50% inhibitory concentration of asiaticoside on MCF-7 cell proliferation. MCF-7 cells were treated with 10, 20, 30, 40, and 50 MUM asiaticoside for 48 h and then incubated with 59.2 MBq of either (99m)Tc-Tfos or (99m)Tc-MIBI tracer for 60 min. The uptake of the tracers was measured with a dose calibrator. RESULTS: The 50% inhibitory concentration of asiaticoside for MCF-7 cells was determined with the MTT assay to be 40 MUM. The uptake results were expressed as the mean +/- SE radioactivity in MBq/mg of protein, and P values were also calculated (P values of 0.03 indicated significant differences). In the control (no asiaticoside) and at 10, 20, 30, 40, and 50 MUM asiaticoside, the mean levels of (99m)Tc-Tfos uptake were 0.79 (SE, 0.059) (P = 0.14), 0.84 (SE, 0.057) (P = 0.60), 0.47 (SE, 0.034) (P = 0.03), 0.40 (SE, 0.050) (P = 0.03), 0.37 (SE, 0.050) (P = 0.03), and 0.15 (SE, 0.023) (P = 0.03), respectively; the mean levels of (99m)Tc-MIBI uptake were 0.95 (SE, 0.007) (P = 0.14), 0.81 (SE, 0.009) (P = 0.60), 0.79 (SE, 0.019) (P = 0.03), 0.63 (SE, 0.004) (P = 0.03), 0.13 (SE, 0.006) (P = 0.03), and 0.07 (SE, 0.008) (P = 0.03), respectively. Asiaticoside concentrations of 10, 20, 30, 40, and 50 MUM revealed the uptake kinetics for both (99m)Tc-Tfos and (99m)Tc-MIBI in MCF-7 cells. (99m)Tc-Tfos and (99m)Tc-MIBI showed similar trends; the radioactivity uptake was dose dependent, and asiaticoside inhibited 16% and 47% of (99m)Tc-Tfos uptake and (99m)Tc-MIBI uptake in MCF-7 cells, respectively. CONCLUSION: This study showed that asiaticoside, acting as a biochemical modulator, may induce apoptosis and enhance antitumor activity in MCF-7 cells, as determined by (99m)Tc-Tfos and (99m)Tc-MIBI uptake. These findings are promising for cancer chemotherapy. Future studies should be performed to confirm our findings and to further delineate the clinical role of asiaticoside. PMID- 22080438 TI - Costimulatory protein 4IgB7H3 drives the malignant phenotype of glioblastoma by mediating immune escape and invasiveness. AB - PURPOSE: Recent work points out a role of B7H3, a member of the B7-family of costimulatory proteins, in conveying immunosuppression and enforced invasiveness in a variety of tumor entities. Glioblastoma is armed with effective immunosuppressive properties resulting in an impaired recognition and ineffective attack of tumor cells by the immune system. In addition, extensive and diffuse invasion of tumor cells into the surrounding brain tissue limits the efficacy of local therapies. Here, 4IgB7H3 is assessed as diagnostic and therapeutic target for glioblastoma. EXPERIMENTAL DESIGN: To characterize B7H3 in glioblastoma, we conduct analyses not only in glioma cell lines and glioma-initiating cells but also in human glioma tissue specimens. RESULTS: B7H3 expression by tumor and endothelial cells correlates with the grade of malignancy in gliomas and with poor survival. Both soluble 4IgB7H3 in the supernatant of glioma cells and cell bound 4IgB7H3 are functional and suppress natural killer cell-mediated tumor cell lysis. Gene silencing showed that membrane and soluble 4IgB7H3 convey a proinvasive phenotype in glioma cells and glioma-initiating cells in vitro. These proinvasive and immunosuppressive properties were confirmed in vivo by xenografted 4IgB7H3 gene silenced glioma-initiating cells, which invaded significantly less into the surrounding brain tissue in an orthotopic model and by subcutaneously injected LN-229 cells, which were more susceptible to natural killer cell-mediated cytotoxicity than unsilenced control cells. CONCLUSIONS: Because of its immunosuppressive and proinvasive function, 4IgB7H3 may serve as a therapeutic target in the treatment of glioblastoma. PMID- 22080439 TI - A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies. AB - PURPOSE: The antibody-drug conjugate (ADC) brentuximab vedotin comprises a CD30 directed antibody covalently attached to the potent antimicrotubule agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. This study explored the safety, maximum-tolerated dose (MTD), and activity of weekly dosing of brentuximab vedotin in patients with relapsed or refractory CD30-positive hematologic malignancies. EXPERIMENTAL DESIGN: In this phase I dose-escalation study, brentuximab vedotin was administered intravenously on Days 1, 8, and 15, of each 28-day cycle at doses ranging from 0.4 to 1.4 mg/kg. Forty-four patients were enrolled: 38 with Hodgkin lymphoma, five with systemic anaplastic large cell lymphoma, and one with peripheral T-cell lymphoma not otherwise specified. Doses were escalated in increments of 0.2 mg/kg until dose-limiting toxicity (DLT) was observed. Patients were monitored for antitherapeutic antibodies and pharmacokinetic parameters. Antitumor assessments were carried out every two cycles. RESULTS: The MTD was 1.2 mg/kg. The most common adverse events were peripheral sensory neuropathy, fatigue, nausea, diarrhea, arthralgia, and pyrexia; and the majority of events were mild to moderate in severity. Tumor regression occurred in 85% of patients and the overall objective response rate was 59% (n = 24), with 34% (n = 14) complete remissions. The median duration of response was not reached at a median follow-up of 45 weeks on study. CONCLUSIONS: Weekly administration of brentuximab vedotin resulted in tumor regression and durable remissions in patients with CD30-positive malignancies. This ADC was associated with manageable toxicity, including peripheral neuropathy. Further study in CD30-positive malignancies is warranted. PMID- 22080440 TI - Punctate LC3B expression is a common feature of solid tumors and associated with proliferation, metastasis, and poor outcome. AB - PURPOSE: Measurement of autophagy in cancer and correlation with histopathologic grading or clinical outcomes has been limited. Accordingly, we investigated LC3B as an autophagosome marker by analyzing nearly 1,400 tumors from 20 types of cancer, focusing on correlations with clinical outcomes in melanoma and breast cancer. EXPERIMENTAL DESIGN: Staining protocols were developed for automated quantitative analysis (AQUA) using antibodies versus LC3 isoform B (LC3B) and Ki 67. Clinically annotated breast and melanoma tissue microarrays (TMA) and a multitumor array were used. An AQUA program was developed to quantitate LC3B distribution in punctate and diffuse compartments of the cell. RESULTS: LC3B staining was moderate to high in the large majority of tumors. The percentage of area occupied by punctate LC3B was elevated by 3- to 5-fold at high LC3B intensities. In breast cancer and melanoma TMAs, LC3B and Ki-67 showed strong correlations (P < 0.0001), and in multitumor TMAs, mitotic figures were most often seen in tumors with the highest LC3B expression (P < 0.002). In breast cancer, LC3B expression was elevated in node-positive versus node-negative primaries and associated with increased nuclear grade and shortened survival. In a melanoma TMA with no survival data, LC3B levels were highest in nodal, visceral, and cutaneous metastases. CONCLUSIONS: The results reveal a common expression of LC3B in malignancy and support emerging evidence that autophagy plays a significant role in cancer progression. High LC3B was associated proliferation, invasion and metastasis, high nuclear grade, and worse outcome. Thus, autophagy presents a key target of therapeutic vulnerability in solid tumors. PMID- 22080441 TI - Pubertal androgenization and gonadal histology in two 46,XY adolescents with NR5A1 mutations and predominantly female phenotype at birth. AB - OBJECTIVE: Most patients with NR5A1 (SF-1) mutations and poor virilization at birth are sex-assigned female and receive early gonadectomy. Although studies in pituitary-specific Sf-1 knockout mice suggest hypogonadotropic hypogonadism, little is known about endocrine function at puberty and on germ cell tumor risk in patients with SF-1 mutations. This study reports on the natural course during puberty and on gonadal histology in two adolescents with SF-1 mutations and predominantly female phenotype at birth. DESIGN AND METHODS: Clinical and hormonal data and histopathological studies are reported in one male and one female adolescent with, respectively, a nonsense mutation (c.9T>A, p.Tyr3X) and a deletion of the first two coding exons (NCBI36/hg18 Chr9:g.(126306276 126307705)_(126303229-126302828)del) of NR5A1, both predicted to fully disrupt gene function. RESULTS: LH and testosterone concentrations were in the normal male range, virilization was disproportionate to the neonatal phenotype. In the girl, gonadectomy at 13 years revealed incomplete spermatogenesis and bilateral precursor lesions of testicular carcinoma in situ. In the boy, at the age of 12, numerous germ cells without signs of malignancy were present in bilateral testicular biopsy specimen. CONCLUSIONS: In SF-1 mutations, the neonatal phenotype poorly predicts virilization at puberty. Even in poorly virilized cases at birth, male gender assignment may allow spontaneous puberty without signs of hypogonadotropic hypogonadism, and possibly fertility. Patients with SF-1 mutations are at increased risk for malignant germ cell tumors. In case of preserved gonads, early orchidopexy and germ cell tumor screening is warranted. The finding of premalignant and/or malignant changes should prompt gonadectomy or possibly irradiation. PMID- 22080442 TI - A small-scale anatomic model for testicular radiation dosimetry for radionuclides localized in the human testes. AB - The testis is a radiosensitive tissue. It contains a large number of lobules, which in turn are composed of convoluted seminiferous tubules. The epithelium inside each tubule consists of a complex mosaic of supporting cells and germ cells of different sizes and degrees of maturation. These cells are known to have diverse sensitivity to radiation, those with the highest sensitivity being the spermatogonia, which form part of the basal cell layer, and those with the lowest sensitivity being the mature sperm cells closest to the lumen of the tubule. For many years, the internal dosimetry community has discussed the need for improvements to bring about more detailed, cell-level testicular dosimetry. This paper presents a small-scale dosimetry model for calculation of S factors for several different source-target configurations within the testicular tissue. METHODS: A model of the testis was designed in which the lobules were approximated by a cross-section of seminiferous tubules arranged in a hexagonal pattern, with interstitial tissue between them. The seminiferous tubules were divided into concentric layers representing spermatogenic development in the seminiferous epithelium. S factors were calculated for electrons, photons, alpha particles, and for (18)F, (90)Y, (99m)Tc, (111)In, (125)I, (131)I, (177)Lu, and (211)At using Monte Carlo simulations. RESULTS: For electrons with low energies the range was small, compared with the diameter of the seminiferous tubules, resulting in high energy deposition close to the source, whereas for higher electron energies more uniform energy deposition was seen, as expected. The same trend was seen for low-energy photons, whose mean free paths are small, compared with the diameter of the seminiferous tubules, resulting in high energy deposition close to the source, whereas for higher photon energies the location of the activity in the testis is less important. CONCLUSION: The model presented in this paper is a simplification of the organized chaos that constitutes the structure of the actual testis. However, it provides a relevant, small-scale anatomic model to help us understand the significance of the heterogeneity of radioactivity in this important radiosensitive tissue. PMID- 22080443 TI - Bombesin antagonist-based radioligands for translational nuclear imaging of gastrin-releasing peptide receptor-positive tumors. AB - Bombesin receptors are overexpressed on a variety of human tumors. In particular, the gastrin-releasing peptide receptor (GRPr) has been identified on prostate and breast cancers and on gastrointestinal stromal tumors. The current study aims at developing clinically translatable bombesin antagonist-based radioligands for SPECT and PET of GRPr-positive tumors. METHODS: A potent bombesin antagonist (PEG(4)-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH(2) [AR]) was synthesized; conjugated to the chelators DOTA, 6-carboxy-1,4,7,11-tetraazaundecane (N4), 1,4,7 triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA), and 4,11 bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (CB-TE2A); and radiolabeled with (111)In, (99m)Tc, (68)Ga, and (64)Cu, respectively. The radioconjugates were evaluated in vitro and in vivo in PC-3 tumor-bearing nude mice. Antagonist potency was determined by Ca(2+)-flux measurements and immunofluorescence. RESULTS: All the conjugates showed high binding affinity to GRPr (inhibitory concentration of 50% [IC(50)], 2.5-25 nmol/L). The immunofluorescence and Ca(2+)-flux assays confirmed the antagonist properties of the conjugates. Biodistribution revealed high and specific uptake in PC-3 tumor and in GRPr-positive tissues. Tumor uptake of (64)Cu-CB-TE2A-AR (31.02 +/- 3.35 percentage injected activity per gram [%IA/g]) was higher than (99m)Tc-N4-AR (24.98 +/- 5.22 %IA/g), (111)In-DOTA-AR (10.56 +/- 0.70 %IA/g), and (68)Ga-NODAGA AR (7.11 +/- 3.26 %IA/g) at 1 h after injection. Biodistribution at later time points showed high tumor-to-background ratios because of the fast washout of the radioligand from normal organs, compared with tumor. High tumor-to-background ratios were further illustrated by PET and SPECT images of PC-3 tumor-bearing nude mice acquired at 12 h after injection showing high tumor uptake, clear background, and negligible or no radioactivity in the abdomen. CONCLUSION: The chelators do influence the affinity, antagonistic potency, and pharmacokinetics of the conjugates. The promising preclinical results warrant clinical translation of these probes for SPECT and PET. PMID- 22080445 TI - Virtual reality for dose optimization in pediatric nuclear medicine: better than the real thing. PMID- 22080444 TI - Effect of patient arm motion in whole-body PET/CT. AB - Arm motion during whole-body PET/CT acquisition is not uncommon and can give rise to striking cold artifacts on PET images. We investigated the mechanisms that underlie these artifacts and proposed a potential solution. METHODS: A phantom experiment based on 5 clinical cases of suspected arm motion was designed. The experiment involved a central 20-cm-diameter (68)Ge/(68)Ga cylinder simulating the neck and 2 peripheral 10-cm-diameter (18)F cylinders simulating arms. After motion-free CT and PET on a whole-body PET/CT system, the position of the arms was altered so as to introduce different amounts of misalignment. Twenty sequential PET scans were acquired in this position, alternating between 2 dimensional (2D) and 3-dimensional (3D) acquisition, as the (18)F decayed. Decay of (18)F in the arms, while the activity in the (68)Ge/(68)Ga cylinder remained approximately constant, allowed the relative impact of scatter and attenuation correction errors to be determined. RESULTS: Image artifacts were largely confined to the local region of motion in 2D but extended throughout the affected slices in 3D, where they manifested as a striking underestimation of radiotracer concentration that became more significant with increasing misalignment. For 3D, scatter-correction error depended on activity in the arms, but for typical activity concentrations scatter-correction error was more significant than attenuation-correction error. 3D image reconstruction without scatter correction substantially eliminated these artifacts in both phantom and patient images. CONCLUSION: Reconstruction artifacts due to patient arm motion can be substantial and should be recognized because they can affect both qualitative and quantitative assessment of PET. PMID- 22080446 TI - Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging. AB - Over the past several years, nuclear imaging modalities such as PET and SPECT have received much attention because they have been instrumental not only in preclinical cancer research but also in nuclear medicine. Yet nuclear imaging is limited by high instrumentation cost and subsequently low availability to basic researchers. Cerenkov radiation, a relativistic physical phenomenon that was discovered 70 years ago, has recently become an intriguing subject of study in molecular imaging because of its potential in augmenting nuclear imaging, particularly in preclinical small-animal studies. The intrinsic capability of radionuclides emitting luminescent light from decay is promising because of the possibility of bridging nuclear imaging with optical imaging-a modality that is much less expensive, is easier to use, and has higher throughput than its nuclear counterpart. Thus, with the maturation of this novel imaging technology using Cerenkov radiation, which is termed Cerenkov luminescence imaging, it is foreseeable that advances in both nuclear imaging and preclinical research involving radioisotopes will be significantly accelerated in the near future. PMID- 22080447 TI - Performance measurements of the Siemens mMR integrated whole-body PET/MR scanner. AB - The recently released Biograph mMR is the first commercially available integrated whole-body PET/MR scanner. There are considerable advantages to integrating both modalities in a single scanner that enables truly simultaneous acquisition. However, there are also concerns about the possible degradation of both PET and MR performance in an integrated system. This paper evaluates the performance of the Biograph mMR during independent and simultaneous acquisition of PET and morphologic MR data. METHODS: The NEMA NU 2-2007 protocol was followed for studying the PET performance. The following measurements were performed: spatial resolution; scatter fraction, count losses, and randoms; sensitivity; accuracy of the correction for count losses and randoms; and image quality. The quality control manual of the American College of Radiology was followed for studying the MR performance. The following measurements were performed: geometric accuracy, spatial resolution, low-contrast detectability, signal-to-noise ratio, static field (B(0)) homogeneity, radiofrequency field (B(1)) homogeneity, and radiofrequency noise. RESULTS: An average spatial resolution of 4.3 mm in full width at half maximum was measured at 1 cm offset from the center of the field of view. The system sensitivity was 15.0 kcps/MBq along the center of the scanner. The scatter fraction was 37.9%, and the peak noise-equivalent count rate was 184 kcps at 23.1 kBq/mL. The maximum absolute value of the relative count rate error due to dead-time losses and randoms was 5.5%. The average residual error in scatter and attenuation correction was 12.1%. All MR parameters were within the tolerances defined by the American College of Radiology. B(0) inhomogeneities below 1 ppm were measured in a 120-mm radius. B(1) homogeneity and signal-to noise ratio were equivalent to those of a standard MR scanner. No radiofrequency interference was detected. CONCLUSION: These results compare favorably with other state-of-the-art PET/CT and PET/MR scanners, indicating that the integration of the PET detectors in the MR scanner and their operation within the magnetic field do not have a perceptible impact on the overall performance. The MR subsystem performs essentially like a standalone system. However, further work is necessary to evaluate the more advanced MR applications, such as functional imaging and spectroscopy. PMID- 22080448 TI - A flash-drag effect in random motion reveals involvement of preattentive motion processing. AB - The flash-drag (FDE) effect refers to the phenomenon in which the position of a stationary flashed object in one location appears shifted in the direction of nearby motion. Over the past decade, it has been debated how bottom-up and top down processes contribute to this illusion. In this study, we demonstrate that randomly phase-shifting gratings can produce the FDE. In the random motion sequence we used, the FDE inducer (a sinusoidal grating) jumped to a random phase every 125 ms and stood still until the next jump. Because this random sequence could not be tracked attentively, it was impossible for the observer to discern the jump direction at the time of the flash. By sorting the data based on the flash's onset time relative to each jump time in the random motion sequence, we found that a large FDE with a broad temporal tuning occurred around 50 to 150 ms before the jump and that this effect was not correlated with any other jumps in the past or future. These results suggest that as few as two frames of unpredictable apparent motion can preattentively cause the FDE with a broad temporal tuning. PMID- 22080449 TI - Two-dimensional speckle tracking echocardiography in heart transplant patients: three-year follow-up of deformation parameters and ejection fraction derived from transthoracic echocardiography. AB - AIMS: Non-invasive diagnosis of allograft dysfunction is a major objective in the management of heart transplant (HTX) recipients. Speckle tracking echocardiography (STE) permits comprehensive assessment of myocardial function. It is well established that deformation indices are reduced in HTXs when compared with control subjects. However, it is unclear if the reduction in strain is a chronic progressive phenomenon in HTX patients. Method and results Follow-up transthoracic echocardiography (TTE) was performed 3 years after initial TTE in 20 'healthy' HTX patients (13.2 years post-transplantation at time of follow-up) with normal ejection fraction and angiographically ruled out allograft vasculopathy. Grey-scale apical views were recorded and stored for automated offline speckle tracking (EchoPAC 7.0, GE) of the 16 segments of the left ventricle. Strain analysis was performed in 320 segments 34.3 +/- 3.7 months after initial assessment. Automated tracking of myocardial deformation for determination of longitudinal systolic strain was not possible in 24 (7.5%) segments at baseline and in 32 (10.0%) segments at follow-up (P = ns). The left ventricular ejection fraction (LVEF) was 61.9 +/- 8.1% at the initial examination vs. 62.8 +/- 5.8% 3 years afterwards (P = ns). Global longitudinal peak systolic strain was -14.0 +/- 4.0 vs. -14.4 +/- 2.8%, respectively (P = ns). CONCLUSION: This is the first study describing follow-up deformation parameters in HTX patients undergoing STE. 'Healthy' HTX patients with normal coronary arteries and normal ejection fractions showed no deterioration of longitudinal strain values 3 years after the initial assessment. Apparently, deformation values remain stable over the years as long as the LVEF is preserved. PMID- 22080450 TI - Relationship between aortic valve stenosis, its replacement, and aortic function. PMID- 22080451 TI - Is viability still viable after the STICH trial? AB - Stunning and hibernation represent two different forms of tissue viability identifiable in acute coronary syndromes and chronic ischaemic cardiomyopathy, respectively. Functional recovery occurs spontaneously with myocardial stunning, while it generally follows revascularization in case of hibernating myocardium. Low-dose dobutamine stress echocardiography is an accurate modality for identifying myocardial stunning and provides important information on ventricular remodelling after both systemic thrombolysis and primary angioplasty. In patients with conservatively treated infarction, the prognostic significance of viability by dobutamine stress echocardiography correlates with residual pump function. Substantial contractile reserve is predictive of favourable outcome in patients with poor but not in those with preserved or slightly reduced left ventricular function. Non-invasive assessment of coronary flow reserve with transthoracic Doppler echocardiography of the left anterior descending coronary artery allows to distinguish between necrotic and stunned myocardium and predicts ventricular remodelling following primary angioplasty. Resting echocardiographic examination can provide information on hibernating myocardium. In particular, systolic thickening <7 mm, restrictive filling pattern, and high end-systolic volume are predictive of no viability. Compared with nuclear imaging, dobutamine stress echocardiography is more specific for predicting functional recovery, less expensive, more generally available and radiation-free. A large body of evidence collected over the years demonstrates the favourable prognostic impact of revascularizing extensive myocardial territories which are found viable at dobutamine stress echocardiography in patients with ischaemic cardiomyopathy. The prognostic implications of viability-guided revascularization have been clearly established in both diabetic and non-diabetic patients. However, the prognostic value of myocardial viability has been questioned by the results of the STICH trial that did not demonstrate any advantage of survival in the patients with a large extent of myocardial viability undergoing revascularization. Is the end of a paradigm that deeply influenced clinical practice so far or just a neutral result that can be ignored due to the several limitations of study design? In the present review, we will address the main advantages and limitations of ultrasounds for the evaluation of myocardial viability and try to demonstrate that viability is still viable. PMID- 22080452 TI - Cardiac involvement in Erdheim-Chester disease: echocardiographic appearance and value of cardiac MRI. PMID- 22080453 TI - Neddylation and CAND1 independently stimulate SCF ubiquitin ligase activity in Candida albicans. AB - SCF (Skp1-cullin/Cdc53-F-box protein) ubiquitin ligases bind substrates via the variable F-box protein and, in conjunction with the RING domain protein Rbx1 and the ubiquitin-conjugating enzyme Ubc3/Cdc34, catalyze substrate ubiquitination. The cullin subunit can be modified covalently by conjugation of the ubiquitin like protein Rub1/NEDD8 (neddylation) or bound noncovalently by the protein CAND1 (cullin-associated, neddylation-dissociated). Expression of the Candida albicans CAND1 gene homolog CaTIP120 in Saccharomyces cerevisiae is toxic only in the presence of CaCdc53, consistent with a specific interaction between CaTip120 and CaCdc53. To genetically analyze this system in C. albicans, we deleted the homologs of RUB1/NEDD8, TIP120/CAND1, and the deneddylase gene JAB1, and we also generated a temperature-sensitive allele of the essential CaCDC53 gene by knock in site-directed mutagenesis. Deletion of CaRUB1 and CaTIP120 caused morphological, growth, and protein degradation phenotypes consistent with a reduction in SCF ubiquitin ligase activity. Furthermore, the double Carub1(-/-) Catip120(-/-) mutant was more defective in SCF activity than either individual deletion mutant. These results indicate that CAND1 stimulates SCF ubiquitin ligase activity and that it does so independently of neddylation. Our data do not support a role for CAND1 in the protection of either the F-box protein or cullin from degradation but are consistent with the suggested role of CAND1 in SCF complex remodeling. PMID- 22080455 TI - Prevalence changes of pain, sleep problems and fatigue among 8-year-old children: years 1989, 1999, and 2005. AB - OBJECTIVES: To study prevalence changes of self-reported pain, sleep problems, and fatigue among 8-year-old children, and to examine the co-occurrence and associated psychosocial variables of these symptoms. METHODS: 3 cross-sectional representative samples were compared in 1989, 1999, and 2005. The frequency of headache, abdominal pain, other pains, sleep problems, and fatigue were studied. In addition, sociodemographic information and child's psychiatric problems were inquired. RESULTS: The prevalence of abdominal pain, sleep problems, and fatigue, in addition to headache in boys and other pains in girls increased significantly (p < .05) from 1989 to 2005, with cumulative odds ratio (95% confidence intervals) varying from 1.6 (1.2-2.1) to 2.4 (1.7-3.3). All symptoms were associated with each other and with the child's psychiatric problems. However, psychiatric problems did not explain the observed increase in the symptom frequencies. CONCLUSIONS: Finnish children's self-reported pain, sleep problems, and fatigue have increased remarkably. Studies providing information on the causes and prevention possibilities are warranted. PMID- 22080454 TI - A flucytosine-responsive Mbp1/Swi4-like protein, Mbs1, plays pleiotropic roles in antifungal drug resistance, stress response, and virulence of Cryptococcus neoformans. AB - Cryptococcosis, caused by the basidiomycetous fungus Cryptococcus neoformans, is responsible for more than 600,000 deaths annually in AIDS patients. Flucytosine is one of the most commonly used antifungal drugs for its treatment, but its resistance and regulatory mechanisms have never been investigated at the genome scale in C. neoformans. In the present study, we performed comparative transcriptome analysis by employing two-component system mutants (tco1Delta and tco2Delta) exhibiting opposing flucytosine susceptibility. As a result, a total of 177 flucytosine-responsive genes were identified, and many of them were found to be regulated by Tco1 or Tco2. Among these, we discovered an APSES-like transcription factor, Mbs1 (Mbp1- and Swi4-like protein 1). Expression analysis revealed that MBS1 was regulated in response to flucytosine in a Tco2/Hog1 dependent manner. Supporting this, C. neoformans with the deletion of MBS1 exhibited increased susceptibility to flucytosine. Intriguingly, Mbs1 played pleiotropic roles in diverse cellular processes of C. neoformans. Mbs1 positively regulated ergosterol biosynthesis and thereby affected polyene and azole drug susceptibility. Mbs1 was also involved in genotoxic and oxidative stress responses. Furthermore, Mbs1 promoted production of melanin and capsule and thereby was required for full virulence of C. neoformans. In conclusion, Mbs1 is considered to be a novel antifungal therapeutic target for treatment of cryptococcosis. PMID- 22080456 TI - Treatment adherence in adolescents with inflammatory bowel disease: the collective impact of barriers to adherence and anxiety/depressive symptoms. AB - OBJECTIVE: Knowledge of factors impacting adolescents' ability to adhere to their inflammatory bowel disease (IBD) regimen is limited. The current study examines the collective impact of barriers to adherence and anxiety/depressive symptoms on adolescent adherence to the IBD regimen. METHODS: Adolescents (n = 79) completed measures of barriers to adherence, adherence, and anxiety/depressive symptoms at one of two specialty pediatric IBD clinics. RESULTS: Most adolescents reported barriers to adherence and 1 in 8 reported borderline or clinically elevated levels of anxiety/depressive symptoms. Anxiety/depressive symptoms moderated the relationship between barriers to adherence and adherence. Post hoc probing revealed a significant, additive effect of higher anxiety/depressive symptoms in the barriers-adherence relationship, with adherence significantly lower among adolescents with higher barriers and higher anxiety/depressive symptoms. CONCLUSIONS: In order to optimize adherence in adolescents, interventions should target not only barriers to adherence but also any anxiety/depressive symptoms that may negatively impact efforts to adhere to recommended treatment. PMID- 22080457 TI - Treatment adherence in pediatric eosinophilic gastrointestinal disorders. AB - OBJECTIVE: Examine treatment adherence rates in pediatric eosinophilic gastrointestinal disorders (EGID). METHODS: Participants were children aged 2.5 18 years with eosinophilic esophagitis or eosinophilic gastroenteritis (EGE) and their caregivers. A multimethod, multi-informant assessment including parent report and electronic monitoring was utilized, with a 90% cut point for nonadherence. RESULTS: Medication nonadherence prevalence was 30%. Adherence frequency was 91% +/- 14% (0-100%) per parent report and 100% +/- 69% (0-194%) per electronic monitors. Tube-feeding adherence was 99% +/- 3%. Food allergen exposures were less than 1 per 2 weeks, with 33% nonadherence prevalence. Patients with EGE and toddlers with both conditions demonstrated poorer medication adherence (p's < .05). Caregivers reported higher number of missed medication doses than food exposures (p < .05). CONCLUSIONS: The prevalence and range of nonadherence demonstrates that subsets of these patients are nonadherent. Adherence to treatment in EGID is complex and multifaceted, with nonadherence varying across treatments. PMID- 22080458 TI - Perthes' disease: deprivation and decline. AB - INTRODUCTION: Perthes' disease is a childhood hip disorder which frequently precipitates premature osteoarthritis necessitating joint replacement in young adults. The highest incidence reported worldwide is in Merseyside, UK, where a unique disease register is maintained. OBJECTIVE: To describe the temporal trends in disease incidence in a geographically defined area of Merseyside, and to examine the relationship to area deprivation. DESIGN: Descriptive observational study utilising a regional disease register in Merseyside, UK, 1976-2009. PATIENTS: 1082 children with Perthes' disease (682 from a geographically defined area). OUTCOME: Disease incidence by region, year and deprivation quintile (measured by the Index of Multiple Deprivation 2007, and the Child Well-Being Index 2009). RESULTS: There was a dramatic decline in incidence over the study period in Liverpool, with rates falling from 14.2 to 7.7 cases/10,000 0-14-year olds (p<0.001). Incidence rates halved in nearby Knowsley (p=0.01) but remained largely static in the more affluent region of Sefton, where the annual incidence remained at around 7.2 cases/10,000 0-14-year-olds (p=0.73). The association with area deprivation is striking, with the most deprived quintiles having over three times the incidence of the most affluent quintiles (11.5 vs 3.8 cases/10,000 0-14 year-olds; p<0.001). Incidence by electoral ward was strongly correlated to ward deprivation score (p<0.001). CONCLUSION: There was a marked decline in disease incidence over the study period, particularly in more deprived areas. The magnitude of the association with deprivation, and the changing incidence, strongly suggest that environmental factor(s) are a major aetiological determinant in Perthes' disease. PMID- 22080459 TI - Improved junior paediatric prescribing skills after a short e-learning intervention: a randomised controlled trial. AB - OBJECTIVE: Medication errors are common, with junior doctors accounting for the majority in acute healthcare. Paediatrics is uniquely challenging, but the evidence base to guide prescribing education is limited. The authors set out to develop a short, educationally sound, low cost e-learning resource for paediatric prescribing to improve junior doctors' prescribing skills and to evaluate its effectiveness. DESIGN: A non-blinded randomised controlled trial. SETTING: North Western Deanery Foundation School, UK. PARTICIPANTS: 162 volunteer foundation (junior) doctors randomised into control (86) and intervention (76) groups. INTERVENTIONS: On study entry, participants were assessed on prescribing skill, prescribing habits and confidence. The intervention group completed the e learning course designed for the study, which took 1-2 h. At 1 and 3 months after the intervention, both groups were assessed on similar prescribing assessments, habits and confidence. MAIN OUTCOME MEASURES: Total score (expressed as a percentage) on prescribing assessments, confidence and satisfaction scores. RESULTS: There were no preintervention differences in prescribing assessments (67% vs 67%, p=0.56). Postintervention, the e-learning group scored significantly higher than the control group (63% vs 79%, p<0.0001). At 3 months, the e-learning group still scored significantly higher (69% vs 79%, p<0.0001), with improved confidence scores (p<0.0001). CONCLUSIONS: This short e-learning resource significantly improved the paediatric prescribing skills of junior doctors. Outcomes were maintained at 3 months, suggesting the utility of low cost, low fidelity, educationally sound e-learning interventions. However, the direct impact on patient outcomes following this intervention has yet to be determined. PMID- 22080460 TI - Towards evidence based medicine for paediatricians. Confident in predicting? Meta analysis models, step two. PMID- 22080461 TI - Question 1. Is there an increased risk of necrotising enterocolitis in preterm infants whose mothers' expressed breast milk is fortified with multicomponent fortifier? PMID- 22080462 TI - Question 2. Should carbon dioxide detectors be used to check correct placement of endotracheal tubes in preterm and term neonates? PMID- 22080463 TI - Question 3. Is measurement of the lymphocyte count useful in the investigation of suspected pertussis in infants? PMID- 22080464 TI - Accurate quantification of cardiovascular biomarkers in serum using Protein Standard Absolute Quantification (PSAQTM) and selected reaction monitoring. AB - Development of new biomarkers needs to be significantly accelerated to improve diagnostic, prognostic, and toxicity monitoring as well as therapeutic follow-up. Biomarker evaluation is the main bottleneck in this development process. Selected Reaction Monitoring (SRM) combined with stable isotope dilution has emerged as a promising option to speed this step, particularly because of its multiplexing capacities. However, analytical variabilities because of upstream sample handling or incomplete trypsin digestion still need to be resolved. In 2007, we developed the PSAQTM method (Protein Standard Absolute Quantification), which uses full length isotope-labeled protein standards to quantify target proteins. In the present study we used clinically validated cardiovascular biomarkers (LDH-B, CKMB, myoglobin, and troponin I) to demonstrate that the combination of PSAQ and SRM (PSAQ-SRM) allows highly accurate biomarker quantification in serum samples. A multiplex PSAQ-SRM assay was used to quantify these biomarkers in clinical samples from myocardial infarction patients. Good correlation between PSAQ-SRM and ELISA assay results was found and demonstrated the consistency between these analytical approaches. Thus, PSAQ-SRM has the capacity to improve both accuracy and reproducibility in protein analysis. This will be a major contribution to efficient biomarker development strategies. PMID- 22080465 TI - How to write a systematic review of reasons. AB - Systematic reviews, which were developed to improve policy-making and clinical decision-making, answer an empirical question based on a minimally biased appraisal of all the relevant empirical studies. A model is presented here for writing systematic reviews of argument-based literature: literature that uses arguments to address conceptual questions, such as whether abortion is morally permissible or whether research participants should be legally entitled to compensation for sustaining research-related injury. Such reviews aim to improve ethically relevant decisions in healthcare, research or policy. They are better tools than informal reviews or samples of literature with respect to the identification of the reasons relevant to a conceptual question, and they enable the setting of agendas for conceptual and empirical research necessary for sound policy-making. This model comprises prescriptions for writing the systematic review's review question and eligibility criteria, the identification of the relevant literature, the type of data to extract on reasons and publications, and the derivation and presentation of results. This paper explains how to adapt the model to the review question, literature reviewed and intended readers, who may be decision-makers or academics. Obstacles to the model's application are described and addressed, and limitations of the model are identified. PMID- 22080466 TI - Multifunctional proteins revealed by overlapping clustering in protein interaction network. AB - MOTIVATION: Multifunctional proteins perform several functions. They are expected to interact specifically with distinct sets of partners, simultaneously or not, depending on the function performed. Current graph clustering methods usually allow a protein to belong to only one cluster, therefore impeding a realistic assignment of multifunctional proteins to clusters. RESULTS: Here, we present Overlapping Cluster Generator (OCG), a novel clustering method which decomposes a network into overlapping clusters and which is, therefore, capable of correct assignment of multifunctional proteins. The principle of OCG is to cover the graph with initial overlapping classes that are iteratively fused into a hierarchy according to an extension of Newman's modularity function. By applying OCG to a human protein-protein interaction network, we show that multifunctional proteins are revealed at the intersection of clusters and demonstrate that the method outperforms other existing methods on simulated graphs and PPI networks. AVAILABILITY: This software can be downloaded from http://tagc.univ mrs.fr/welcome/spip.php?rubrique197 CONTACT: brun@tagc.univ-mrs.fr SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22080468 TI - BadiRate: estimating family turnover rates by likelihood-based methods. AB - MOTIVATION: The comparative analysis of gene gain and loss rates is critical for understanding the role of natural selection and adaptation in shaping gene family sizes. Studying complete genome data from closely related species allows accurate estimation of gene family turnover rates. Current methods and software tools, however, are not well designed for dealing with certain kinds of functional elements, such as microRNAs or transcription factor binding sites. RESULTS: Here, we describe BadiRate, a new software tool to estimate family turnover rates, as well as the number of elements in internal phylogenetic nodes, by likelihood based methods and parsimony. It implements two stochastic population models, which provide the appropriate statistical framework for testing hypothesis, such as lineage-specific gene family expansions or contractions. We have assessed the accuracy of BadiRate by computer simulations, and have also illustrated its functionality by analyzing a representative empirical dataset. AVAILABILITY: BadiRate software and documentation is available from http://www.ub.edu/softevol/badirate. PMID- 22080469 TI - Assessment of ELF magnetic fields produced by independent power lines. AB - In this paper, the problem of assessing the ELF (extremely low-frequency) magnetic fields produced, in a certain area characterised by the presence of more than one independent power line, is faced. The use of the incoherent summation of the single contributions, as an advantageous estimator of the total magnetic field, is proposed and justified by means of a heuristic procedure. This kind of approach can be seen as a useful and practical tool to be employed in environmental impact analysis and in assessing long-term human exposure to ELF magnetic fields. PMID- 22080467 TI - Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers. AB - MOTIVATION: Genome-wide mRNA profiling provides a snapshot of the global state of cells under different conditions. However, mRNA levels do not provide direct understanding of upstream regulatory mechanisms. Here, we present a new approach called Expression2Kinases (X2K) to identify upstream regulators likely responsible for observed patterns in genome-wide gene expression. By integrating chromatin immuno-precipitation (ChIP)-seq/chip and position weight matrices (PWMs) data, protein-protein interactions and kinase-substrate phosphorylation reactions, we can better identify regulatory mechanisms upstream of genome-wide differences in gene expression. We validated X2K by applying it to recover drug targets of food and drug administration (FDA)-approved drugs from drug perturbations followed by mRNA expression profiling; to map the regulatory landscape of 44 stem cells and their differentiating progeny; to profile upstream regulatory mechanisms of 327 breast cancer tumors; and to detect pathways from profiled hepatic stellate cells and hippocampal neurons. The X2K approach can advance our understanding of cell signaling and unravel drugs mechanisms of action. AVAILABILITY: The software and source code are freely available at: http://www.maayanlab.net/X2K. CONTACT: avi.maayan@mssm.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22080470 TI - Indoor radon and thoron levels in Neendakara and Chavara regions of southern coastal Kerala, India. AB - Some areas of the world, called high background radiation areas (HBRAs), have anomalously high levels of natural background radiation and the population residing in the areas is exposed to higher levels of radiation doses than other parts of the world where the natural radioactivity contents are normal. In the present investigation, levels of radon, thoron and their progeny are studied in 110 houses in the coastal region of the Kollam district in the state of Kerala, India using the multi-detector twin cup dosimeter. Among these, 10 houses were studied in detail with five dosimeters in each house. Radon activity concentrations were found to vary from 7 to 100 Bqm(-3) and that of thoron from 4 to 66 Bqm(-3) in Neendakara panchayat. In Chavara panchayat, the variations of radon concentrations were from 7 to 83 Bqm(-3) and thoron concentrations were varied from 4 to 86 Bqm(-3). The occurrence of radon and thoron concentrations in the dwellings for both study areas shows that in 50% of the dwellings, the concentration of radon is about 25 Bqm(-3) and in 60% of the dwellings thoron concentration is about 15 Bqm(-3). The ratio of thoron-to-radon concentrations in the dwellings showed a mean value 0.55 (GM=0.45) for the region. PMID- 22080471 TI - Haemoptysis as a complication of pacemaker implantation. PMID- 22080472 TI - In-hospital follow-up of implantable cardioverter defibrillator and pacemaker carriers: patients' inconvenience and points of view. A four-hospital Italian survey. AB - AIMS: The increasing volume of pacemaker (PM) and implantable cardioverter defibrillator (ICD) implants and problems related to their functioning have highlighted the issue of device follow-ups. Patients' convenience regarding device visits has been little investigated. This work aims at surveying patients' efforts in attending the in-office PM/ICD follow-ups and at evaluating their expectations. METHODS AND RESULTS: In four Italian referral centres, over a 3 month period, a 20-point questionnaire was completed by all consecutive patients at in-hospital PM/ICD visits. In total, 1109 questionnaire/patients were evaluated. Pacemakers were 68%, ICDs 16%, and cardiac resynchronizations (CRTs) (PM + ICD) 16%; 38% were females; mean age was 75 +/- 11 years. Almost all were scheduled visits. There was frequent reprogramming and clinical examination, even after 6 months from implant. Perceived inconvenience for the in-office follow-up was relevant in 35% of cases; attitudes towards remote monitoring were positive in 88% of cases. Inter-group analysis showed some significant difference: PM patients were older and more frequently female; ICD carriers were younger, had the highest rate of clinical evaluation, a longer journey time, and the most positive opinion about remote follow-up. Cardiac resynchronization patients had a longer waiting time and the lowest inconvenience. Overall inconvenience was independently predicted by increasing age, lengthy travelling times, and being accompanied; favourable opinions about remote monitoring were predicted by overall inconvenience, and, in ICD carriers only, by lack of clinical examination. CONCLUSIONS: Patients' perceptions of in-hospital PM/ICD visits were affected by age and by journey modalities. Individual factors seem to affect both opinions about in-office visits and expectations towards a possible remote follow up. PMID- 22080473 TI - Efficacy and safety of ventricular tachycardia ablation with mechanical circulatory support compared with substrate-based ablation techniques. AB - AIMS: Catheter ablation of ventricular tachycardia (VT) can be limited by haemodynamic instability. In these cases, substrate-based ablation is typically performed. An alternative is to perform activation and entrainment mapping during VT supported by a percutaneous left ventricular assist device (pVAD). We sought to compare the complication and success rates of pVAD-assisted VT ablation with scar-based techniques. METHODS AND RESULTS: Thirteen consecutive patients with haemodynamically unstable VT underwent pVAD-assisted ablation (pVAD group) and were retrospectively compared with 18-matched patients undergoing a substrate based VT ablation (non-pVAD group). There was no significant difference in age or ejection fraction between the groups although pVAD patients tended to have more shocks in the preceding months. Procedure times were longer for the pVAD group. The number of monomorphic VTs induced was greater in the pVAD group (3.2 vs. 1.6, P= 0.04); however, after ablation, there was no difference in inducibility between the pVAD and non-pVAD group (10 of 13 vs. 12 of 18; 77 vs. 67%, P = 0.69). There was no difference in acute complications including stroke or death. At 9 +/- 3 months, 1-year freedom from implantable cardioverter-defibrillator (ICD) shocks/therapies for sustained VT were similar (P= 0.96). In multivariable analysis, the absence of atrial fibrillation (hazard ratio=0.15, P= 0.04) was associated with a lower incidence of ICD shocks. CONCLUSIONS: In high-risk patients, pVAD-assisted VT ablation guided by activation and entrainment mapping is a feasible alternative to substrate mapping and allows outcomes comparable to substrate mapping. PMID- 22080474 TI - Pre-discharge defibrillation testing: clinically important or obsolete? PMID- 22080475 TI - SMBE proposal to the government of Japan. PMID- 22080476 TI - Harmonization may be counterproductive--at least for parts of Europe where public health research operates effectively. PMID- 22080477 TI - Cochrane eye and vision group. PMID- 22080478 TI - Retinal oxygen saturation is altered in diabetic retinopathy. AB - AIM: Retinal oxygen metabolism is thought to be affected in diabetic retinopathy. The aim of this study was to test whether retinal vessel oxygen saturation is different in patients with diabetic retinopathy from that in healthy controls. METHODS: The retinal oximeter is based on a fundus camera. It estimates retinal vessel oxygen saturation from light absorbance at 586 nm and 605 nm. Retinal vessel oxygen saturation was measured in one major temporal retinal arteriole and venule in healthy volunteers and in patients with diabetic retinopathy. RESULTS: Oxygen saturation in the retinal arterioles of healthy volunteers was 93 +/- 4% and 58 +/- 6% in venules (mean +/- SD, n=31). The corresponding values for all diabetic patients (n=20) were 101 +/- 5% and 68 +/- 7%. The difference between healthy volunteers and diabetic patients was statistically significant (p < 0.001 for arterioles and venules). Three subgroups of diabetic patients (background retinopathy, macular oedema and pre-proliferative/proliferative retinopathy) all had higher saturation values than the healthy volunteers (p < 0.05 for arterioles and venules). CONCLUSION: Retinal vessel oxygen saturation is higher in patients with diabetic retinopathy than in healthy controls. Possible explanations include shunting of blood through preferential channels, bypassing non-perfused capillaries in the capillary network. Parts of the retinal tissue may be hypoxic while blood in larger vessels has high oxygen saturation. PMID- 22080479 TI - STEAP1 is associated with the invasive and oxidative stress phenotype of Ewing tumors. AB - Ewing tumors comprise the second most common type of bone-associated cancer in children and are characterized by oncogenic EWS/FLI1 fusion proteins and early metastasis. Compelling evidence suggests that elevated levels of intracellular oxidative stress contribute to enhanced aggressiveness of numerous cancers, possibly including Ewing tumors. Using comprehensive microarray analyses and RNA interference, we identified the six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-a membrane-bound mesenchymal stem cell marker of unknown function-as a highly expressed protein in Ewing tumors compared with benign tissues and show its regulation by EWS/FLI1. In addition, we show that STEAP1 knockdown reduces Ewing tumor proliferation, anchorage-independent colony formation as well as invasion in vitro and decreases growth and metastasis of Ewing tumor xenografts in vivo. Moreover, transcriptome and proteome analyses as well as functional studies revealed that STEAP1 expression correlates with oxidative stress responses and elevated levels of reactive oxygen species that in turn are able to regulate redox-sensitive and proinvasive genes. In synopsis, our data suggest that STEAP1 is associated with the invasive behavior and oxidative stress phenotype of Ewing tumors and point to a hitherto unanticipated oncogenic function of STEAP1. PMID- 22080481 TI - Buruli ulcer in an 18-day-old baby. AB - Buruli ulcer is an indolent disease that needs aggressive curettage of caseous subcutaneous tissue beneath the undermined skin. We report the successful treatment of an 18-day-old baby. PMID- 22080480 TI - Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies. AB - The mammalian target of rapamycin (mTOR) plays crucial roles in proliferative and antiapoptotic signaling in lymphoid malignancies. Rapamycin analogs, which are allosteric mTOR complex 1 (mTORC1) inhibitors, are active in mantle cell lymphoma and other lymphoid neoplasms, but responses are usually partial and short-lived. In the present study we compared the effects of rapamycin with the dual mTORC1/mTORC2 inhibitor OSI-027 in cell lines and clinical samples representing divers lymphoid malignancies. In contrast to rapamycin, OSI-027 markedly diminished proliferation and induced apoptosis in a variety of lymphoid cell lines and clinical samples, including specimens of B-cell acute lymphocytic leukemia (ALL), mantle cell lymphoma, marginal zone lymphoma and Sezary syndrome. Additional analysis demonstrated that OSI-027-induced apoptosis depended on transcriptional activation of the PUMA and BIM genes. Overexpression of Bcl-2, which neutralizes Puma and Bim, or loss of procaspase 9 diminished OSI-027 induced apoptosis in vitro. Moreover, OSI-027 inhibited phosphorylation of mTORC1 and mTORC2 substrates, up-regulated Puma, and induced regressions in Jeko xenografts. Collectively, these results not only identify a pathway that is critical for the cytotoxicity of dual mTORC1/mTORC2 inhibitors, but also suggest that simultaneously targeting mTORC1 and mTORC2 might be an effective anti lymphoma strategy in vivo. PMID- 22080482 TI - Percutaneous endoscopic gastrostomy tube replacement. AB - Percutaneous endoscopic gastrostomy (PEG) is undertaken in order to provide long term nutrition in patients with dysphagia. Over time, the PEG tubes will deteriorate and will need to be replaced. We describe a method of replacement which is cost-effective and which does not require repetition of the endoscopy. PMID- 22080483 TI - Variable clinical presentations of histoplasmosis: a report of six cases. AB - Histoplasma is a dimorphic fungus that primarily involves the lungs and the environmental reservoir is soil. It has emerged as an important opportunistic fungal infection in immunocompromised patients. Six cases of histoplasmosis with variable clinical presentations diagnosed either on cytology or histopathology are discussed - three were HIV-positive. The possibility of histoplasmosis should always be borne in mind, especially in immunocompromised patients, as it can have variable clinical presentations. PMID- 22080484 TI - Multi-drug-resistant tuberculosis: the experience of an urban tertiary care hospital in South India using automated BACTEC 460 TB. AB - The emergence of multi-drug-resistant (MDR) strains has been a major obstacle in the tuberculosis (TB) control programme. In the present study we looked into the prevalence of MDR-TB in an urban tertiary care hospital in South India over four years (2007-2010). During this period, 641 clinical specimens (317 respiratory specimens and 324 non-respiratory specimens) were received for mycobacteriological culture and drug susceptibility testing for first-line drugs, using the BACTEC 460 TB system. Mycobacterium tuberculosis (MTB) was isolated in 34.8% (n = 223) specimens. Of the total 223 MTB isolates 83 (37.2%) were MDR. Forty-two percent of the pulmonary MTB isolates (n = 72) and 20.4% of the extra pulmonary isolates (n = 10) were MDR. Although we observed a high percentage of drug resistance, the prevalence of MDR was not observed to vary significantly within the four years which suggested good management. PMID- 22080485 TI - Effect of changes in intrathoracic pressure on cardiac function at rest and during moderate exercise in health and heart failure. AB - This study investigated the effect of changes in inspiratory intrathoracic pressure on stroke volume at rest and during moderate exercise in patients with heart failure and reduced ejection fraction (HFREF) as well as healthy individuals. Stroke volume was obtained by echocardiography during 2 min of spontaneous breathing (S), two progressive levels of inspiratory unloading (UL1 and UL2) using a ventilator, and two progressive levels of inspiratory loading using resistors in 11 patients with HFREF (61 +/- 9 years old; ejection fraction 32 +/- 4%; NYHA class I-II) and 11 age-matched healthy individuals at rest and during exercise at 60% of maximal aerobic capacity on a semi-recumbent cycle ergometer. At rest, inspiratory unloading progressively decreased stroke volume index (SVI; S, 35.2 +/- 5.4 ml m(-2); UL1, 33.3 +/- 5.1 ml m(-2); and UL2, 32.2 +/- 4.4 ml m(-2)) in healthy individuals, while it increased SVI (S, 31.4 +/- 4.6 ml m(-2); UL1, 32.0 +/- 5.9 ml m(-2); and UL2, 34.0 +/- 7.2 ml m(-2)) in patients with HFREF (P = 0.04). During moderate exercise, inspiratory unloading decreased SVI in a similar manner (S, 43.9 +/- 7.1 ml m(-2); UL1, 40.7 +/- 4.7 ml m(-2); and UL2, 39.9 +/- 3.7 ml m(-1)) in healthy individuals, while it increased SVI (S, 40.8 +/- 6.5 ml m(-2); UL1, 42.8 +/- 6.9 ml m(-2); and UL2, 44.1 +/- 4. ml m( 2)) in patients with HFREF (P = 0.02). Inspiratory loading did not significantly change SVI at rest or during moderate exercise in both groups. It is concluded that inspiratory unloading improved SVI at rest and during moderate exercise in patients with HFREF, possibly due to a reduction in left ventricular afterload. PMID- 22080486 TI - Exercise normalizes altered expression of proteins in the ventral hippocampus of rats subjected to maternal separation. AB - Many studies have reported on the detrimental effects of early life adversity and the beneficial effects of exercise on brain function. However, the molecular mechanisms that underpin these various effects remain poorly understood. The advent of advanced proteomic analysis techniques has enabled simultaneous measurement of protein expression in a wide range of biological systems. We therefore used iTRAQ proteomic analysis of protein expression to determine whether exercise counteracts the detrimental effects of early life adversity in the form of maternal separation on protein expression in the brain. Rat pups were subjected to maternal separation from postnatal day 2 to 14 for 3 h day(-1) or normally reared. At 40 days of age, half of the rats in each group (maternal separation and normally reared) were allowed to exercise voluntarily (access to a running wheel) for 6 weeks and the remainder kept as sedentary control animals. At 83 days of age, rats were killed and the ventral hippocampus was dissected for quantitative proteomic (iTRAQ) analysis. The iTRAQ proteomic analysis identified several proteins that had been altered by maternal separation, including proteins involved in neuronal structure, metabolism, signalling, anti-oxidative stress and neurotransmission, and that many of these proteins were restored to normal by subsequent exposure to voluntary exercise in adolescence. Our data show that a broad range of proteins play a role in the complex consequences of adversity and exercise. PMID- 22080488 TI - Why India needs a national nutrition strategy. PMID- 22080487 TI - Involvement of cyclo-oxygenase-1-mediated prostacyclin synthesis in the vasoconstrictor activity evoked by ACh in mouse arteries. AB - This study was to determine whether the endothelium of mouse major arteries produces prostacyclin (PGI(2)) and, if so, to determine how PGI(2) affects vasomotor reactivity and whether cyclo-oxygenase-1 (COX-1) contributes to PGI(2) synthesis. Abdominal aortas, carotid and femoral arteries were isolated from wild type mice and/or those with COX-1 or -2 deficiency (COX-1(-/-); COX-2(-/-)) for biochemical and/or functional analyses. The PGI(2) metabolite 6-keto-PGF(1alpha) was analysed with high-performance liquid chromatography-mass spectroscopy, while vasoreactivity was determined with isometric force measurement. Results showed that in the abdominal aorta, ACh evoked endothelium-dependent production of 6 keto-PGF(1alpha), which was abolished by COX-1(-/-), but not by COX-2(-/-). Interestingly, COX-1(-/-) enhanced the dilatation in response to ACh, while PGI(2), which evoked relaxation of the mesenteric artery, caused contraction that was abolished by antagonizing thromboxane prostanoid (TP) receptors in the abdominal aorta. However, the TP receptor agonist U46619 evoked similar contractions in the abdominal aorta and mesenteric artery. Also, antagonizing TP receptors enhanced the relaxation in response to PGI(2) in mesenteric arteries. Real-time PCR showed that the PGI(2) (IP) receptor mRNA level was lower in the abdominal aorta than in mesenteric arteries. In addition, COX-1(-/-) not only abolished the contraction in response to ACh following NO inhibition in abdominal aorta, but also those in the carotid and femoral arteries. These results demonstrate an explicit role for endothelial COX-1 in PGI(2) synthesis and suggest that in given mouse arteries, PGI(2) mediates not dilatation but rather vasoconstrictor activity, possibly due to a low expression or functional presence of IP receptors, which enables PGI(2) to act mainly on TP receptors. PMID- 22080489 TI - Commentary: Cultural change is essential. PMID- 22080490 TI - EEG can pick up brain activity in people in vegetative state, shows study. PMID- 22080491 TI - Microbial domestication signatures of Lactococcus lactis can be reproduced by experimental evolution. AB - Experimental evolution is a powerful approach to unravel how selective forces shape microbial genotypes and phenotypes. To this date, the available examples focus on the adaptation to conditions specific to the laboratory. The lactic acid bacterium Lactococcus lactis naturally occurs on plants and in dairy environments, and it is proposed that dairy strains originate from the plant niche. Here we investigate the adaptation of a L. lactis strain isolated from a plant to a dairy niche by propagating it for 1000 generations in milk. Two out of three independently evolved strains displayed significantly increased acidification rates and biomass yields in milk. Genome resequencing, revealed six, seven, and 28 mutations in the three strains, including point mutations in loci related to amino acid biosynthesis and transport and in the gene encoding MutL, which is involved in DNA mismatch repair. Two strains lost a conjugative transposon containing genes important in the plant niche but dispensable in milk. A plasmid carrying an extracellular protease was introduced by transformation. Although improving growth rate and growth yield significantly, the plasmid was rapidly lost. Comparative transcriptome and phenotypic analyses confirmed that major physiological changes associated with improved growth in milk relate to nitrogen metabolism and the loss or down-regulation of several pathways involved in the utilization of complex plant polymers. Reproducing the transition from the plant to the dairy niche through experimental evolution revealed several genome, transcriptome, and phenotype signatures that resemble those seen in strains isolated from either niche. PMID- 22080492 TI - Mobile Assessment and Treatment for Schizophrenia (MATS): a pilot trial of an interactive text-messaging intervention for medication adherence, socialization, and auditory hallucinations. AB - Mobile Assessment and Treatment for Schizophrenia (MATS) employs ambulatory monitoring methods and cognitive behavioral therapy interventions to assess and improve outcomes in consumers with schizophrenia through mobile phone text messaging. Three MATS interventions were developed to target medication adherence, socialization, and auditory hallucinations. Participants received up to 840 text messages over a 12-week intervention period. Fifty-five consumers with schizophrenia or schizoaffective disorder were enrolled, but 13 consumers with more severe negative symptoms, lower functioning, and lower premorbid IQ did not complete the intervention, despite repeated prompting and training. For completers, the average valid response rate for 216 outcome assessment questions over the 12-week period was 86%, and 86% of phones were returned undamaged. Medication adherence improved significantly, but only for individuals who were living independently. Number of social interactions increased significantly and a significant reduction in severity of hallucinations was found. In addition, the probability of endorsing attitudes that could interfere with improvement in these outcomes was also significantly reduced in MATS. Lab-based assessments of more general symptoms and functioning did not change significantly. This pilot study demonstrated that low-intensity text-messaging interventions like MATS are feasible and effective interventions to improve several important outcomes, especially for higher functioning consumers with schizophrenia. PMID- 22080493 TI - Resting-state brain activity in schizophrenia and major depression: a quantitative meta-analysis. AB - Intrinsic activity of the brain during resting-state is not random and is currently discussed as a neural reflection of self-referential processing. Self reference is typically reduced in schizophrenia as a disorder of the self while extensive self-attribution of, eg, negative thoughts is characteristic for major depression. However, a quantitative meta-analysis targeting the resting-state brain activity in both disorders is lacking. Here, we predict primarily abnormal resting-state activity in brain regions related to self-referential processing. By means of activation likelihood estimation (ALE) on functional magnetic resonance imaging and positron emission tomography studies, we investigated concurrence of hyperactivation and hypoactivation in resting-state measurements of schizophrenic and depressed patients compared with healthy controls. We found hypoactivation in ventromedial prefrontal cortex (vmPFC), left hippocampus, posterior cingulate cortex, lower precueus and the precuneus, and hyperactivation in bilateral lingual gyrus of schizophrenic patients. In major depression, we found hyperactivation in vmPFC, left ventral striatum, and left thalamus and hypoactivation in left postcentral gyrus, left fusiform gyrus, and left insula. An overall ALE analysis confirmed the proximity of hypoactivation in schizophrenia and hyperactivation in major depression in the vmPFC.The opposing resting-state activity in vmPFC for the 2 disorders is in line with the different expression of dysfunctional self-reference as core characteristics of schizophrenia and major depression. The vmPFC has previously been identified as a crucial area for self-referential processing and may represent a target to increase the diagnostic validity of resting-state activity for disorders with dysfunctions of the self. PMID- 22080494 TI - Neuroanatomical maps of psychosis onset: voxel-wise meta-analysis of antipsychotic-naive VBM studies. AB - BACKGROUND: Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment. METHODS: Fourteen voxel based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk [HR]) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and "signed differential mapping" voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables. RESULTS: Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results. CONCLUSIONS: Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms. PMID- 22080495 TI - Manipulation of orthogonal neural systems together in electrophysiological recordings: the MONSTER approach to simultaneous assessment of multiple neurocognitive dimensions. AB - Event-related potentials (ERPs) are a powerful tool in understanding and evaluating cognitive, affective, motor, and sensory processing in both healthy and pathological samples. A typical ERP recording session takes considerable time but is designed to isolate only 1-2 components. Although this is appropriate for most basic science purposes, it is an inefficient approach for measuring the broad set of neurocognitive functions that may be disrupted in a neurological or psychiatric disease. The present study provides a framework for more efficiently evaluating multiple neural processes in a single experimental paradigm through the manipulation of functionally orthogonal dimensions. We describe the general MONSTER (Manipulation of Orthogonal Neural Systems Together in Electrophysiological Recordings) approach and explain how it can be adapted to investigate a variety of neurocognitive domains, ERP components, and neural processes of interest. We also demonstrate how this approach can be used to assess group differences by providing data from an implementation of the MONSTER approach in younger (18-30 y of age) and older (65-85 y of age) adult samples. This specific implementation of the MONSTER framework assesses 4 separate neural processes in the visual domain: (1) early sensory processing, using the C1 wave; (2) shifts of covert attention, with the N2pc component; (3) categorization, with the P3 component; and (4) self-monitoring, with the error-related negativity. Although the MONSTER approach is primarily described in the context of ERP experiments, it could also be adapted easily for use with functional magnetic resonance imaging. PMID- 22080496 TI - Disease prediction in the at-risk mental state for psychosis using neuroanatomical biomarkers: results from the FePsy study. AB - BACKGROUND: Reliable prognostic biomarkers are needed for the early recognition of psychosis. Recently, multivariate machine learning methods have demonstrated the feasibility to predict illness onset in clinically defined at-risk individuals using structural magnetic resonance imaging (MRI) data. However, it remains unclear whether these findings could be replicated in independent populations. METHODS: We evaluated the performance of an MRI-based classification system in predicting disease conversion in at-risk individuals recruited within the prospective FePsy (Fruherkennung von Psychosen) study at the University of Basel, Switzerland. Pairwise and multigroup biomarkers were constructed using the MRI data of 22 healthy volunteers, 16/21 at-risk subjects with/without a subsequent disease conversion. Diagnostic performance was measured in unseen test cases using repeated nested cross-validation. RESULTS: The classification accuracies in the "healthy controls (HCs) vs converters," "HCs vs nonconverters," and "converters vs nonconverters" analyses were 92.3%, 66.9%, and 84.2%, respectively. A positive likelihood ratio of 6.5 in the converters vs nonconverters analysis indicated a 40% increase in diagnostic certainty by applying the biomarker to an at-risk population with a transition rate of 43%. The neuroanatomical decision functions underlying these results particularly involved the prefrontal perisylvian and subcortical brain structures. CONCLUSIONS: Our findings suggest that the early prediction of psychosis may be reliably enhanced using neuroanatomical pattern recognition operating at the single-subject level. These MRI-based biomarkers may have the potential to identify individuals at the highest risk of developing psychosis, and thus may promote informed clinical strategies aiming at preventing the full manifestation of the disease. PMID- 22080497 TI - Risk factors for psychosis: impaired social and role functioning. AB - OBJECTIVES: Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. METHODS: Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. RESULTS: At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. CONCLUSIONS: Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long term disability. PMID- 22080498 TI - CNTRICS imaging biomarkers selection: Working memory. AB - The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) consortium was focused on selecting promising imaging biomarker measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of working memory (WM), the 2 constructs of interest were "goal maintenance" and "interference control." CNTRICS received 7 task nominations for goal maintenance and 3 task nominations for interference control. For goal maintenance, the breakout group for WM recommended the AX Continuous Performance Test/Dot Pattern Expectancy (DPX) and the Switching Stroop task for translation and further development for use in clinical trial contexts in schizophrenia research. Notably, these same 2 paradigms were recommended for "rule generation and selection" in executive control, a highly related construct. For interference control, the breakout group recommended the Suppress Task and the Sternberg Item Recognition Paradigm for translation for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used by the breakout group to recommend tasks for further development. In addition, the group revisited the construct of WM capacity. Since the initial CNTRICS meeting, a growing body of work has emerged on the neurobiological substrates of WM capacity, making measure of this construct ready for translation. The group suggested a promising imaging biomarker measure for capacity, a version of the change detection task that measures delay activity over posterior parietal and occipital cortex. PMID- 22080500 TI - Chronic inhibition of the respiratory chain in human fibroblast cultures: differential responses related to subject chronological and biological age. AB - Respiratory chain function becomes less efficient with age resulting in increased levels of damaging reactive oxygen species. We compared rotenone-exposed fibroblast strains from young and old subjects and from offspring of nonagenarian siblings and the partners of the offspring. Rotenone increased reactive oxygen species levels, inhibited growth rate, and increased telomere shortening (all p < .05). Non-stressed strains from young subjects showed lower reactive oxygen species levels (p = .031) and higher growth rates (p = .002) than strains from old subjects. Stressed strains from young subjects showed smaller increases in reactive oxygen species levels (p = .014) and larger decreases in growth rate (p < .001) than strains from old subjects. Telomere-shortening rates were not different between groups. Stress-induced decreases in growth rate were larger in strains from offspring than from partners (p = .05). Strains from young and old subjects are differentially affected by chronic inhibition of the respiratory chain. Changed growth rates in strains from offspring resemble those from strains from young subjects. PMID- 22080501 TI - The association between olfactory impairment and total mortality in older adults. AB - BACKGROUND: Population-based data on the relationship between impaired olfaction and risk of mortality among older adults are lacking. We used a representative cohort of adults aged 60 years or older to assess whether olfactory loss is a predictor of mortality, independent of potential confounders. METHODS: Olfaction was measured by the San Diego Odor Identification Test (SDOIT) among 1,636 participants enrolled in the Blue Mountains Eye Study (2002-2004). Five-year all cause mortality was confirmed using the Australian National Death Index. RESULTS: More than one in five participants (21.8%) with olfactory impairment had died over the 5 years compared with less than 10% of participants without olfactory loss. Moderate olfactory loss (SDOIT score <=3) was associated with a 68% increased risk of all-cause mortality (multivariable-adjusted hazard ratio, 1.68; 95% confidence interval, 1.10-2.56). This association did not persist after further adjustment for cognitive impairment. The association between olfactory loss and all-cause mortality was more marked among older participants (>=70 years) than younger participants (<70 years) with olfactory impairment (multivariable-adjusted hazard ratio, 1.48; 95% confidence interval, 1.02-2.15). However, adjusting for cognitive impairment diminished this association. CONCLUSIONS: Older adults with moderately impaired olfaction compared with those with normal olfaction had a higher risk of dying 5 years later. The relationship between olfaction and mortality, however, may be largely mediated by cognitive impairment in these older adults. Our findings highlight the value of identifying olfactory loss in the preclinical stage in the older patient before the development of related comorbidities. PMID- 22080499 TI - Growth hormone and IGF-1 deficiency exacerbate high-fat diet-induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging. AB - Previous studies suggest that the age-related decline in circulating growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in elderly individuals is increasing at alarming rates, and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging, GH/IGF-1 deficiency, and obesity interact to promote the development of cardiovascular disease remain unclear. To test the hypothesis that low circulating GH/IGF-1 levels exacerbate the pro-oxidant and proinflammatory vascular effects of obesity, GH/IGF-1-deficient Lewis dwarf rats and heterozygous control rats were fed either a standard diet or a high-fat diet (HFD) for 7 months. Feeding an HFD resulted in similar relative weight gains and increases in body fat content in Lewis dwarf rats and control rats. HFD-fed Lewis dwarf rats exhibited a relative increase in blood glucose levels, lower insulin, and impaired glucose tolerance as compared with HFD-fed control rats. Analysis of serum cytokine expression signatures indicated that chronic GH/IGF-1 deficiency exacerbates HFD-induced inflammation. GH/IGF-1 deficiency also exacerbated HFD-induced endothelial dysfunction, oxidative stress, and expression of inflammatory markers (tumor necrosis factor-alpha, ICAM-1) in aortas of Lewis dwarf rats. Overall, our results are consistent with the available clinical and experimental evidence suggesting that GH/IGF-1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity. PMID- 22080502 TI - Age-related effects in working memory recognition modulated by retroactive interference. AB - One of the main causes for age-related declines in working memory is a higher vulnerability to retroactive interference due to a reduced ability to suppress irrelevant information. However, the underlying neural correlates remain to be established. Magnetoencephalography was used to investigate differential neural patterns in young and older adults performing an interference-based memory task with two experimental conditions, interrupting and distracting, during successful recognition. Behaviorally, both types of retroactive interference significantly impaired accuracy at recognition more in older adults than in young adults with the latter exhibiting greater disruptions by interrupters. Magnetoencephalography revealed the presence of differential age-related neural patterns. Specifically, time-modulated activations in temporo-occipital and superior parietal regions were higher in young adults compared with older adults for the interrupting condition. These results suggest that age-related deficits in inhibitory mechanisms that increase vulnerability to retroactive interference may be associated with neural under-recruitments in a high-interference task. PMID- 22080503 TI - Pretend play and development in early childhood (with implications for the oedipal phase). AB - Pretend play reflects both the unique mental organization and the developmental challenges of early to middle childhood, with a trajectory that parallels the monumental transformation of the toddler to the school-age child. Despite evidence for various forms of playing throughout the life cycle, the flowering of symbolic play in this phase is specific, essential, and typically transient in terms of its dominance in the life of the child. It reflects the simultaneous emergence, processing, and integration of the remarkable developmental advances occurring during this period, most especially the capacity to symbolize, in the service of the exponentially expanded psychosexual/social/emotional force field implied in the contemporary use of the term oedipus complex. Moreover, it constitutes a particular mental organization and ego state, with idiosyncratic mentation, affect regulation, and relationship to inner and outer experience, that accompanies the child's gradual orientation to consensual reality. Subsequent access to some form of this state varies widely among individuals but is rarely fully comparable. PMID- 22080504 TI - The neurobiology of fear memory reconsolidation and psychoanalytic theory. AB - Advances in both experimental neuroscience and psychoanalytic theory and technique have made it possible to consider mechanisms by which psychodynamic psychotherapies might have an impact at the cellular and molecular level. Here potential analogies are drawn between (1) the mechanisms and results of blocking the reconsolidation of conditioned fear memories in the laboratory and (2) several key aspects of psychoanalytic process. A review of the biology of conditioned fear memory, including differences between extinction and inhibition of reconsolidation, indicates that this biology may have relevance to various ways in which psychoanalytic therapy is effective. The ideas proposed here might lead to further experimental attempts to understand the molecular biology of psychoanalysis. PMID- 22080505 TI - PSCDB: a database for protein structural change upon ligand binding. AB - Proteins are flexible molecules that undergo structural changes to function. The Protein Data Bank contains multiple entries for identical proteins determined under different conditions, e.g. with and without a ligand molecule, which provides important information for understanding the structural changes related to protein functions. We gathered 839 protein structural pairs of ligand-free and ligand-bound states from monomeric or homo-dimeric proteins, and constructed the Protein Structural Change DataBase (PSCDB). In the database, we focused on whether the motions were coupled with ligand binding. As a result, the protein structural changes were classified into seven classes, i.e. coupled domain motion (59 structural changes), independent domain motion (70), coupled local motion (125), independent local motion (135), burying ligand motion (104), no significant motion (311) and other type motion (35). PSCDB provides lists of each class. On each entry page, users can view detailed information about the motion, accompanied by a morphing animation of the structural changes. PSCDB is available at http://idp1.force.cs.is.nagoya-u.ac.jp/pscdb/. PMID- 22080506 TI - A database of immunoglobulins with integrated tools: DIGIT. AB - The DIGIT (Database of ImmunoGlobulins with Integrated Tools) database (http://biocomputing.it/digit) is an integrated resource storing sequences of annotated immunoglobulin variable domains and enriched with tools for searching and analyzing them. The annotations in the database include information on the type of antigen, the respective germline sequences and on pairing information between light and heavy chains. Other annotations, such as the identification of the complementarity determining regions, assignment of their structural class and identification of mutations with respect to the germline, are computed on the fly and can also be obtained for user-submitted sequences. The system allows customized BLAST searches and automatic building of 3D models of the domains to be performed. PMID- 22080507 TI - Attenuation of loop-receptor interactions with pseudoknot formation. AB - RNA tetraloops can recognize receptors to mediate long-range interactions in stable natural RNAs. In vitro selected GNRA tetraloop/receptor interactions are usually more 'G/C-rich' than their 'A/U-rich' natural counterparts. They are not as widespread in nature despite comparable biophysical and chemical properties. Moreover, while AA, AC and GU dinucleotide platforms occur in natural GAAA/11 nt receptors, the AA platform is somewhat preferred to the others. The apparent preference for 'A/U-rich' GNRA/receptor interactions in nature might stem from an evolutionary adaptation to avoid folding traps at the level of the larger molecular context. To provide evidences in favor of this hypothesis, several riboswitches based on natural and artificial GNRA receptors were investigated in vitro for their ability to prevent inter-molecular GNRA/receptor interactions by trapping the receptor sequence into an alternative intra-molecular pseudoknot. Extent of attenuation determined by native gel-shift assays and co transcriptional assembly is correlated to the G/C content of the GNRA receptor. Our results shed light on the structural evolution of natural long-range interactions and provide design principles for RNA-based attenuator devices to be used in synthetic biology and RNA nanobiotechnology. PMID- 22080508 TI - Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group. AB - The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, can result in the enhancement of siRNA cellular uptake. Herein, the carrier-free cellular uptake of nuclease-resistant anti-MDR1 siRNA equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached to the 5'-end of the sense strand via oligomethylene linker of various length was investigated. A convenient combination of H-phosphonate and phosphoramidite methods was developed for the synthesis of 5'-lipophilic conjugates of siRNAs. It was found that lipophilic siRNA are able to effectively penetrate into HEK293, HepG2 and KB-8-5 cancer cells when used in a micromolar concentration range. The efficiency of the uptake is dependent upon the type of lipophilic moiety, the length of the linker between the moiety and the siRNA and cell type. Among all the conjugates tested, the cholesterol-conjugated siRNAs with linkers containing from 6 to 10 carbon atoms demonstrate the optimal uptake and gene silencing properties: the shortening of the linker reduces the efficiency of the cellular uptake of siRNA conjugates, whereas the lengthening of the linker facilitates the uptake but retards the gene silencing effect and decreases the efficiency of the silencing. PMID- 22080509 TI - Database for bacterial group II introns. AB - The Database for Bacterial Group II Introns (http://webapps2.ucalgary.ca/~groupii/index.html#) provides a catalogue of full length, non-redundant group II introns present in bacterial DNA sequences in GenBank. The website is divided into three sections. The first section provides general information on group II intron properties, structures and classification. The second and main section lists information for individual introns, including insertion sites, DNA sequences, intron-encoded protein sequences and RNA secondary structure models. The final section provides tools for identification and analysis of intron sequences. These include a step-by-step guide to identify introns in genomic sequences, a local BLAST tool to identify closest intron relatives to a query sequence, and a boundary-finding tool that predicts 5' and 3' intron-exon junctions in an input DNA sequence. Finally, selected intron data can be downloaded in FASTA format. It is hoped that this database will be a useful resource not only to group II intron and RNA researchers, but also to microbiologists who encounter these unexpected introns in genomic sequences. PMID- 22080510 TI - KEGG for integration and interpretation of large-scale molecular data sets. AB - Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www.genome.jp/kegg/ or http://www.kegg.jp/) is a database resource that integrates genomic, chemical and systemic functional information. In particular, gene catalogs from completely sequenced genomes are linked to higher-level systemic functions of the cell, the organism and the ecosystem. Major efforts have been undertaken to manually create a knowledge base for such systemic functions by capturing and organizing experimental knowledge in computable forms; namely, in the forms of KEGG pathway maps, BRITE functional hierarchies and KEGG modules. Continuous efforts have also been made to develop and improve the cross-species annotation procedure for linking genomes to the molecular networks through the KEGG Orthology system. Here we report KEGG Mapper, a collection of tools for KEGG PATHWAY, BRITE and MODULE mapping, enabling integration and interpretation of large-scale data sets. We also report a variant of the KEGG mapping procedure to extend the knowledge base, where different types of data and knowledge, such as disease genes and drug targets, are integrated as part of the KEGG molecular networks. Finally, we describe recent enhancements to the KEGG content, especially the incorporation of disease and drug information used in practice and in society, to support translational bioinformatics. PMID- 22080511 TI - ADHDgene: a genetic database for attention deficit hyperactivity disorder. AB - With a worldwide prevalence of ~5%, attention deficit hyperactivity disorder (ADHD) has become one of the most common psychiatric disorders. The polygenetic nature of ADHD indicates that multiple genes jointly contribute to the development of this complex disease. Studies aiming to explore genetic susceptibility of ADHD have been increasing in recent years. There is a growing need to integrate the genetic data from various genetic studies to provide a comprehensive data set and uniform access for convenience of in-depth data mining. So far, there has been no such effort for ADHD. To address the genetic complexity of ADHD, we developed the ADHDgene database by integrating ADHD related genetic factors by profound literature reading. Based on the data from the literature, extended functional analysis, including linkage disequilibrium analysis, pathway-based analysis and gene mapping were performed to provide new insights into genetic causes of ADHD. Moreover, powerful search tools and a graphical browser were developed to facilitate the navigation of the data and data connections. As the first genetic database for ADHD, ADHDgene aims to provide researchers with a central genetic resource and analysis platform for ADHD and is freely available at http://adhd.psych.ac.cn/. PMID- 22080512 TI - Plantmetabolomics.org: mass spectrometry-based Arabidopsis metabolomics--database and tools update. AB - The PlantMetabolomics (PM) database (http://www.plantmetabolomics.org) contains comprehensive targeted and untargeted mass spectrum metabolomics data for Arabidopsis mutants across a variety of metabolomics platforms. The database allows users to generate hypotheses about the changes in metabolism for mutants with genes of unknown function. Version 2.0 of PlantMetabolomics.org currently contains data for 140 mutant lines along with the morphological data. A web-based data analysis wizard allows researchers to select preprocessing and data-mining procedures to discover differences between mutants. This community resource enables researchers to formulate models of the metabolic network of Arabidopsis and enhances the research community's ability to formulate testable hypotheses concerning gene functions. PM features new web-based tools for data-mining analysis, visualization tools and enhanced cross links to other databases. The database is publicly available. PM aims to provide a hypothesis building platform for the researchers interested in any of the mutant lines or metabolites. PMID- 22080513 TI - Interplay between HIV-1 infection and host microRNAs. AB - Using microRNA array analyses of in vitro HIV-1-infected CD4(+) cells, we find that several host microRNAs are significantly up- or downregulated around the time HIV-1 infection peaks in vitro. While microRNA-223 levels were significantly enriched in HIV-1-infected CD4(+)CD8(-) PBMCs, microRNA-29a/b, microRNA-155 and microRNA-21 levels were significantly reduced. Based on the potential for microRNA binding sites in a conserved sequence of the Nef-3'-LTR, several host microRNAs potentially could affect HIV-1 gene expression. Among those microRNAs, the microRNA-29 family has seed complementarity in the HIV-1 3'-UTR, but the potential suppressive effect of microRNA-29 on HIV-1 is severely blocked by the secondary structure of the target region. Our data support a possible regulatory circuit at the peak of HIV-1 replication which involves downregulation of microRNA-29, expression of Nef, the apoptosis of host CD4 cells and upregulation of microRNA-223. PMID- 22080515 TI - Perceived quality of and access to care among poor urban women in Kenya and their utilization of delivery care: harnessing the potential of private clinics? AB - This paper uses data from a maternal health study carried out in 2006 in two slums of Nairobi, Kenya, to: describe perceptions of access to and quality of care among women living in informal settlements of Nairobi, Kenya; quantify the effects of women's perceived quality of, and access to, care on the utilization of delivery services; and draw policy implications regarding the delivery of maternal health services to the urban poor. Based on the results of the facility survey, all health facilities were classified as 'appropriate' or 'inappropriate'. The research was based on the premise that despite the poor quality of these maternal health facilities, their responsiveness to the socio cultural and economic sensitivities of women would result in good perceptions and higher utilization by women. Our results show a pattern of women's good perceptions in terms of access to, and quality of, health care provided by the privately owned, sub-standard and often unlicensed clinics and maternity homes located within their communities. In the multivariate model, the association between women's perceptions of access to and quality of care, and delivery at these 'inappropriate' facilities remained strong, graded and in the expected direction. Women from the study area are seldom able to reach not-for-profit private providers of maternal health care services like missionary and non governmental organization (NGO) clinics and hospitals. Against the backdrop of challenges faced by the public sector in health care provision, we recommend that the government should harness the potential of private clinics operating in urban, resource-deprived settings. First, the government should regulate private health facilities operating in urban slum settlements to ensure that the services they offer meet the acceptable minimum standards of obstetric care. Second, 'good' facilities should be given technical support and supplied with drugs and equipment. PMID- 22080514 TI - PolymiRTS Database 2.0: linking polymorphisms in microRNA target sites with human diseases and complex traits. AB - The polymorphism in microRNA target site (PolymiRTS) database aims to identify single-nucleotide polymorphisms (SNPs) that affect miRNA targeting in human and mouse. These polymorphisms can disrupt the regulation of gene expression by miRNAs and are candidate genetic variants responsible for transcriptional and phenotypic variation. The database is therefore organized to provide links between SNPs in miRNA target sites, cis-acting expression quantitative trait loci (eQTLs), and the results of genome-wide association studies (GWAS) of human diseases. Here, we describe new features that have been integrated in the PolymiRTS database, including: (i) polymiRTSs in genes associated with human diseases and traits in GWAS, (ii) polymorphisms in target sites that have been supported by a variety of experimental methods and (iii) polymorphisms in miRNA seed regions. A large number of newly identified microRNAs and SNPs, recently published mouse phenotypes, and human and mouse eQTLs have also been integrated into the database. The PolymiRTS database is available at http://compbio.uthsc.edu/miRSNP/. PMID- 22080516 TI - UK is the best at coordinating care for sicker patients, Sweden the worst, shows survey. PMID- 22080517 TI - Conservative win in Spain's general election will boost role of private sector in healthcare. PMID- 22080518 TI - England and Wales "achieve more with less" on cancer outcomes than other countries. PMID- 22080519 TI - More than half a million people could lose incapacity benefit after welfare changes. PMID- 22080520 TI - Agencies begin clearing unexploded weapons in Libya. PMID- 22080521 TI - GMC is ordered to pay doctor 22,000 pound after judge quashes panel's findings against her. PMID- 22080522 TI - NHS hospital is taken over by a private social enterprise. PMID- 22080523 TI - GP partners' pay decreases as expenses increase. PMID- 22080524 TI - Anticipated stigma and quality of life among people living with chronic illnesses. AB - OBJECTIVES: We examined the process by which anticipated stigma relates to quality of life among people living with chronic illnesses. We hypothesized that stress, social support and patient satisfaction mediate the relationships between three sources of anticipated stigma and quality of life. METHODS: Data were collected from adults living with chronic illnesses recruited from support groups and online communities, and were analysed with path analysis. RESULTS: Results demonstrated that stress mediated the relationships between anticipated stigma from friends and family, and work colleagues with quality of life; social support mediated the relationships between anticipated stigma from friends and family, and work colleagues with quality of life; and patient satisfaction mediated the relationship between anticipated stigma from healthcare providers with quality of life. The final path model fit the data well (chi (2) (8) = 8.66, p = 0.37; RMSEA = 0.02; CFI = 0.99; SRMR = 0.03), and accounted for 60% of the variance in participants' quality of life. DISCUSSION: This work highlights potential points of intervention to improve quality of life. It calls attention to the importance of differentiating between sources of anticipated stigma in clinical settings, interventions and research involving people living with chronic illnesses. PMID- 22080525 TI - Public health significance of four cardiovascular risk factors assessed 25 years ago in a low prevalence country. AB - BACKGROUND: The individual and combined effect of cardiovascular disease (CVD) risk factors (RFs) on CVD mortality varies between populations. Our aim was to examine this association and its public health impact in Switzerland, a country with comparably low CVD mortality. METHODS: We included 9853 men and women aged 25-74 years who participated in the Swiss MONICA (MONItoring of trends and determinants in CArdiovascular disease) study (1983-1992) and were followed up for survival until 2008. Adjusted Cox regression was used to calculate CVD mortality hazard ratios (HR). CVD-RFs were obesity (body mass index >= 30 kg/m(2)), smoking (>= 1 cig/d), high blood pressure (>= 140 or >= 90 mmHg), and total: high-density lipoprotein cholesterol ratio (>= 5.0). Besides age and sex, models were adjusted for diet, physical activity, educational class, marital status, and the respective other CVD-RFs. RESULTS: After adjustment for age and sex, the HR of CVD death was for obesity 1.86 (95% CI 1.50-2.31), for smoking 1.63 (95% CI 1.32-2.01), for high blood pressure 1.42 (95% CI 1.16-1.73), and for high cholesterol ratio 1.30 (95% CI 1.06-1.60). Adjustment for other covariates moderately attenuated estimates. CVD-RFs had an independent and synergistic effect and accounted for 43.0% of population attributable risk. The presence of all four compared to zero CVD-RFs was associated with a 9.6 years shorter expected survival for a man aged 50. CONCLUSIONS: Most CVD deaths could be avoided by prevention of four traditional CVD-RFs. Reduction of smoking prevalence and avoidance of weight gain in the population are the most effective measures. Particular attention should be dedicated to persons with multiple CVD RFs. PMID- 22080526 TI - Reliability and validity of the five-repetition sit-to-stand test for children with cerebral palsy. AB - OBJECTIVE To investigate the psychometric properties of the five-repetition sit to-stand test, a functional strength test, in children with spastic diplegia. DESIGN: Methodology study. SETTINGS: Hospital, laboratory or home. PARTICIPANTS: In total, 108 children with spastic diplegia and 62 with typical development aged from five to 12 years were tested. For test-retest reliability, 22 children with spastic diplegia were tested twice within one week. INTERVENTIONS: Not applicable. MAIN MEASURES: The five-repetition sit-to-stand test measures time needed to complete five consecutive sit-to-stand cycles as quickly as possible. The higher the rate of five-repetition sit-to-stand (repetitions per second), the more strength a person has. RESULTS: The intraclass correlation coefficients of intra-session reliability and test-retest reliability were 0.95 and 0.99 respectively. The minimal detectable difference was 0.06 rep/sec. The convergent validity of the five-repetition sit-to-stand test was supported by significant correlation with one-repetition maximum of the loaded sit-to-stand test, isometric muscle strength, scores of Gross Motor Function Measure, and gait function (r or rho = 0.40-0.78). For known group validity, children with typical development and children classified as Gross Motor Function Classification System level I performed higher rates of five-repetition sit-to-stand than children classified as level II, and children classified as level II performed higher rates than level III. CONCLUSION: The five-repetition sit-to-stand test was a reliable and valid test to measure functional muscle strength in children with spastic diplegia in clinics. PMID- 22080527 TI - Voxel-based analysis of apparent diffusion coefficient in perihaematomal oedema: associated factors and outcome predictive value for intracerebral haemorrhage. AB - Objectives The pathophysiology of perihaematomal oedema (PO) surrounding a primary intracerebral haemorrhage (ICH) is complicated and incompletely understood. We prospectively investigated the components of PO with voxel-based analysis of the apparent diffusion coefficient (ADC) value and assessed its predictive value for functional outcome. Design Forty-six patients with ICH who were enrolled for clinical evaluation underwent MRI scans within 24 h after ICH. Based on the ADC value of the ipsilateral voxels divided by the mean ADC value of the contralateral mirror region of interest, the voxels with oedema were classified into three categories: cytotoxic, vasogenic and undetermined. The percentages of cytotoxic and vasogenic oedema were then calculated and correlated with clinical outcome according to the modified Rankin Scale (mRS) at 6 months after ICH. The intraobserver and interobserver reliability of this method were examined using intraclass correlation coefficients. Results The intraclass correlation coefficients showed that analysis using the voxel-based method is highly reliable. Among the clinical variables tested, age and serum creatinine levels were positively correlated with percentage of cytotoxic oedema. Age, history of coronary artery disease, National Institutes of Health Stroke Scale score and percentage of cytotoxic oedema were all associated with mRS at 6 months after ICH. Conclusions The pathophysiological processes within PO are complicated. Voxel-based analysis of ADC values may help to identify the components of PO and may be beneficial for decision making and predicting outcome. PMID- 22080528 TI - Differences in coronary heart disease, stroke and cancer mortality rates between England, Wales, Scotland and Northern Ireland: the role of diet and nutrition. AB - Introduction It is unclear how much of the geographical variation in coronary heart disease (CHD), stroke and cancer mortality rates within the UK is associated with diet. The aim of this study is to estimate how many deaths from CHD, stroke and cancer would be delayed or averted if Wales, Scotland and Northern Ireland adopted a diet equivalent in nutritional quality to the English diet. Methods Mortality data for CHD, stroke and 10 diet-related cancers for 2007-2009 were used to calculate the mortality gap (the difference between actual mortality and English mortality rates) for Wales, Scotland and Northern Ireland. Estimates of mean national consumption of 10 dietary factors were used as baseline and counterfactual inputs in a macrosimulation model (DIETRON). An uncertainty analysis was conducted using a Monte Carlo simulation with 5000 iterations. Results The mortality gap in the modelled scenario (achieving the English diet) was reduced by 81% (95% credible intervals: 62% to 108%) for Wales, 40% (33% to 51%) for Scotland and 81% (67% to 99%) for Northern Ireland, equating to approximately 3700 deaths delayed or averted annually. For CHD only, the mortality gap was reduced by 88% (69% to 118%) for Wales, 58% (47% to 72%) for Scotland, and 88% (70% to 111%) for Northern Ireland. Conclusion Improving the average diet in Wales, Scotland and Northern Ireland to a level already achieved in England could have a substantial impact on reducing geographical variations in chronic disease mortality rates in the UK. Much of the mortality gap between Scotland and England is explained by non-dietary risk factors. PMID- 22080529 TI - Management of patient adherence to medications: protocol for an online survey of doctors, pharmacists and nurses in Europe. AB - Introduction It is widely recognised that many patients do not take prescribed medicines as advised. Research in this field has commonly focused on the role of the patient in non-adherence; however, healthcare professionals can also have a major influence on patient behaviour in taking medicines. This study examines the perceptions, beliefs and behaviours of healthcare professionals-doctors, pharmacists and nurses-about patient medication adherence. Methods and analysis This paper describes the study protocol and online questionnaire used in a cross sectional survey of healthcare professionals in Europe. The participating countries include Austria, Belgium, France, Greece, The Netherlands, Germany, Poland, Portugal, Switzerland, Hungary, Italy and England. The study population comprises primary care and community-based doctors, pharmacists and nurses involved in the care of adult patients taking prescribed medicines for chronic and acute illnesses. Discussion Knowledge of the nature, extent and variability of the practices of healthcare professionals to support medication adherence could inform future service design, healthcare professional education, policy and research. PMID- 22080530 TI - Challenges for health promotion research and action across the globe. PMID- 22080531 TI - Neurophysiological and morphological responses to treatment with acetyl-L carnitine in a sciatic nerve injury model: preliminary data. AB - We investigated the effects of acetyl-L-carnitine (ALCAR) on the recovery of sciatic nerve injuries in rats. Sprague Dawley rats were randomized to two groups: ALCAR treated (for 14 days) and control. Each group was divided into three subgroups: distal transection, proximal transection, and grafted. Distal latencies, amplitudes, and motor nerve conduction velocities were measured. In the third month, biopsies were taken and examined under light microscopy. Electrophysiological measurements demonstrated that regeneration occurred earlier and was better in the ALCAR group, particularly in the distal transection subgroup. Better results were obtained in the distal transection subgroup in terms of axonal regeneration compared with the proximal transection and grafted subgroups because the regenerating segment was shorter. ALCAR enhanced the quality of neural recovery at the different levels and in different types of repair, and led to a decline in nerve death. PMID- 22080532 TI - Closed rupture of abductor pollicis longus and extensor pollicis brevis associated with fracture of the distal radius. PMID- 22080533 TI - The tape strip: facilitating radiographic imaging and surgical procedures in the hand. PMID- 22080534 TI - Re: Henderson J, Sutcliffe M, Gillespie P. The tension band principle and angular testing of extensor tendon repairs. J Hand Surg Eur. 2011, 36: 297-302. PMID- 22080535 TI - Child malnutrition and recurrent flooding in rural eastern India: a community based survey. AB - Objectives This study aims to improve the understanding of the relationship between exposure to floods and malnutrition in children aged 6-59 months in rural India. Research has focused exclusively on Bangladeshi children, and few controlled epidemiological studies are available. Method A community-based cross sectional study of child nutritional status was carried out in 14 flooded and 18 non-flooded villages of Jagatsinghpur district (Orissa) within one month of the September 2008 floods, and similarly affected by flooding in August 2006. Face-to face interviews were conducted in 757 households in the flooded villages and 816 in the non-flooded communities. Data used in this study were from those households with children aged 6-59 months. In total, 191 and 161 children were measured, respectively. The association between various malnutrition indicators and the exposure to floods was assessed by univariate and multivariate logistic regression. Results Adjusted analyses revealed that children in flooded households were more likely stunted compared with those in non-flooded ones (adjusted prevalence ratio 1.60; 95% CI 1.05 to 2.44). The prevalence of underweight was also higher in children living in the flooded communities (adjusted prevalence ratio 1.86; 95% CI 1.04 to 3.30). Further analyses found that the 26-36-month flooded cohort, thus those children younger than 1 year during the precedent flood in August 2006, attained the largest difference in levels of stunting compared with the unexposed group of the same age. Conclusion Exposure to floods is associated with long-term malnutrition in these rural communities of Orissa, India. Children exposed to floods during their first year of life presented higher levels of chronic malnutrition. Long-term malnutrition prevention programmes after floods should be implemented in flood-prone areas. PMID- 22080536 TI - Prospective Swiss cohort study of living-kidney donors: study protocol. AB - Background Offering living kidney donation raised the concern that donors are exposed to unknown risks. All Swiss transplant centres therefore decided to start a prospective cohort study of living kidney donors in Switzerland. This paper describes the rationale for and implementation of this cohort study. Methods/design All kidney donors in Switzerland are registered and examined before donation and biennially after donation starting in the first year after nephrectomy. Before each follow-up visit, the study centre sends a package to the kidney donor containing the health questionnaire, blood and urine tubes and a prepaid envelope for sending the samples to the central laboratory. The donor makes an appointment with their family physician, who examines the donor and reports findings such as pain and other complaints, blood pressure, creatinine, albumin, all major health events and the state of mental and social well-being to the study centre. The family doctor draws the blood sample and mails it with the urine sample in the prepaid envelope. All data are centrally managed. All abnormal findings in the follow-up of individual donors are regularly discussed with the principal investigator, and necessary clinical changes made and recorded in the database. The health insurance of the recipient covers all costs of the donor follow-up. The main outcomes are the occurrence of albuminuria, hypertension and renal insufficiency. The secondary outcomes are major somatic and social events such as death, cardiovascular disease, stroke and depression. Discussion This prospective cohort offers unique opportunities to assess the risks of living kidney donation and will allow us to examine the risks associated with the methods used for nephrectomy in Switzerland (various forms of open surgery and laparoscopic nephrectomy). The prospective collection of all clinically relevant data and the regular monitoring of donors will allow timely interventions at early stages before serious kidney and general health problems occur. PMID- 22080537 TI - Training the biomedical informatics workforce in Latin America: results of a needs assessment. AB - Objective To report the results of a needs assessment of research and training in Medical Informatics (MI) and Bioinformatics (BI) in Latin America. Methods and results This assessment was conducted by QUIPU: The Andean Global Health Informatics Research and Training Center. After sending email invitations to MI BI related professionals from Latin America, 142 surveys were received from 11 Latin American countries. The following were the top four ranked MI-related courses that a training programme should include: introduction to biomedical informatics; data representation and databases; mobile health; and courses that address issues of security, confidentiality and privacy. Several new courses and topics for research were suggested by survey participants. The information collected is guiding the development of curricula and a research agenda for the MI and BI QUIPU multidisciplinary programme for the Andean Region and Latin America. PMID- 22080538 TI - Epidemiology of syphilis-related hospitalisations in Spain between 1997 and 2006: a retrospective study. AB - Objective In order to illustrate the important public health impact of syphilis, which is a preventable infection, the epidemiology of syphilis-related hospitalisations in Spain was studied over a 10-year period. Methods A retrospective study was conducted using the National Epidemiological Surveillance System for Hospital Data (Minimum Data Set). All hospitalisations due to syphilis infection in any diagnostic position (ICD-9-CM 090-097) between 1997 and 2006 were analysed, according to the Spanish version of the International Classification of Diseases, ninth revision (ICD-9-CM). Results There were 9556 hospitalisations associated with syphilis in Spain. The hospitalisation rate was 2.33 per 100 000 population, the mortality rate was 0.07 per 100 000 population and the lethality was 3.17%. The hospitalisation rate increased significantly after 2000 and was higher in men. Conclusion Syphilis remains a major public health problem because of both potential complications and its close association with HIV infection. It is necessary to promote early diagnosis, ensure treatment in patients with syphilis and emphasise health promotion and prevention programmes. PMID- 22080539 TI - Mortality from Parkinson's disease and other causes among a workforce manufacturing paraquat: a retrospective cohort study. AB - Objective To assess the risk of Parkinson's disease (PD) and update information on mortality from major causes of death among a UK workforce who manufactured paraquat (PQ) between 1961 and 1995. There have been no previous studies of the incidence of PD among PQ production workers, although much epidemiological literature exists concerning the relationship between pesticides and PD, and interest has focused on PQ and its users. Methods The cohort included all employees who had ever worked on any of the four plants at Widnes where PQ was manufactured between 1961 and 1995, and 926 male and 42 female workers were followed through 30 June 2009. Mortalities for males were compared with national and local rates, including rates for PD as a mentioned cause of death. Results Overall, 307 workers had died by 30 June 2009. One male death was due to PD, and no other death certificate mentioned PD. At least 3.3 death certificates of male employees would have been expected to have mentioned PD (standardised mortality ratio=31; 95% CI 1 to 171). Personal monitoring results were indicative that the exposure of a PQ production worker on a daily basis was at least comparable with that of a PQ sprayer or mixer/loader. Reduced mortalities compared with local rates were found for major causes of death. Conclusions The study provided no evidence of an increased risk of PD, or increased mortalities from other causes. PMID- 22080540 TI - Characteristics of randomised trials on diseases in the digestive system registered in ClinicalTrials.gov: a retrospective analysis. AB - Objectives To evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published trials. Methods Randomised phase III trials on adult patients with gastrointestinal diseases registered before January 2009 in http://ClinicalTrials.gov were eligible for inclusion. From http://ClinicalTrials.gov all data elements in the database required by the International Committee of Medical Journal Editors (ICMJE) member journals were extracted. The subsequent publications for registered trials were identified. For published trials, data concerning publication date, primary and secondary endpoint, sample size, and whether the journal adhered to ICMJE principles were extracted. Differences between primary and secondary outcomes, sample size and sample size calculations data in http://ClinicalTrials.gov and in the published paper were registered. Results 105 trials were evaluated. 66 trials (63%) were published. 30% of trials were registered incorrectly after their completion date. Several data elements of the required ICMJE data list were not filled in, with missing data in 22% and 11%, respectively, of cases concerning the primary outcome measure and sample size. In 26% of the published papers, data on sample size calculations were missing and discrepancies between sample size reporting in http://ClinicalTrials.gov and published trials existed. Conclusion The quality of registration of randomised controlled trials still needs improvement. PMID- 22080541 TI - The 'Eigenstandig werden' prevention trial: a cluster randomised controlled study on a school-based life skills programme to prevent substance use onset. AB - Objective To implement and evaluate 'Eigenstandig werden 5+6' ('Becoming Independent 5+6'), a school-based curriculum for grades 5 and 6 developed on the basis of evidence-based criteria for effective drug prevention curricula in schools. Evaluation of the programme includes efficacy, feasibility and practicability in daily school routine. Methods and results The intervention 'Eigenstandig werden 5+6' consists of 14 teaching units evenly distributed over grades 5 and 6 which are interactively delivered, and a parent component. Programme effects are studied in a four wave cluster randomised controlled trial with two arms, an intervention and a control group. Self-completed questionnaires from students and teachers are collected by trained research staff. 45 schools, 172 classes and 3444 students with a mean age of 10.37 years (SD=0.59) and 47.9% girls from four federal states in Germany were assessed at baseline. 1685 students in 81 classes were assigned to intervention classes, 1759 students in 91 classes to the control arm. No differences between conditions were found for age, gender, immigration background, socioeconomic status, substance use or life skills at baseline. Exceptions were higher self-efficacy (t(3438)=2.34, p=0.02, d=0.08) and empathy (t(3302)=2.4, p=0.02, d=0.09) in the control group, whereas class climate seemed better in the intervention group (t(3037)=2.01, p=0.05, d=0.07), but effect sizes state marginal differences. Conclusion Baseline data suggest that the initial conditions are favourable for testing programme efficacy since distribution of baseline levels of the outcomes did not differ in the intervention and control groups, except for negligible differences between self efficacy and empathy, which were higher in the control group, and class climate, which was higher in the intervention group. Trial registration number Current Controlled Trials ISRCTN99442407. PMID- 22080542 TI - What determines adherence to treatment in cardiovascular disease prevention? Protocol for a mixed methods preference study. AB - Background Significant gaps exist between guidelines-recommended therapies for cardiovascular disease prevention and current practice. Fixed-dose combination pills ('polypills') potentially improve adherence to therapy. This study is a preference study undertaken in conjunction with a clinical trial of a polypill and seeks to examine the underlying reasons for variations in treatment adherence to recommended therapy. Methods/design A preference study comprising: (1) Discrete Choice Experiment for patients; and (2) qualitative study of patients and providers. Both components will be conducted on participants in the trial. A joint model combining the observed adherence in the clinical trial (revealed preference) and the Discrete Choice Experiment data (stated preference) will be estimated. Estimates will be made of the marginal effect (importance) of each attribute on overall choice, the extent to which respondents are prepared to trade-off one attribute for another and predicted values of the level of adherence given a fixed set of attributes, and contextual and socio-demographic characteristics. For the qualitative study, a thematic analysis will be used as a means of exploring in depth the preferences and ultimately provide important narratives on the experiences and perspectives of individuals with regard to adherence behaviour. Ethics and dissemination Primary ethics approval was received from Sydney South West Area Health Service Human Research Ethics Committee (Royal Prince Alfred Hospital zone). In addition to usual scientific forums, the findings will be reported back to the communities involved in the studies through site-specific reports and oral presentations. PMID- 22080543 TI - Postoperative atrial fibrillation predicts long-term survival after aortic-valve surgery but not after mitral-valve surgery: a retrospective study. AB - Background Postoperative atrial fibrillation (POAF) has been reported to be associated with reduced long-term survival after isolated coronary artery bypass grafting surgery. The objective of this study was to determine the impact of POAF on long-term survival after valvular surgery. Methods The authors retrospectively analysed the preoperative and operative data of 2986 consecutive patients with no preoperative history of atrial fibrillation undergoing first valvular surgery (aortic-valve replacement (AVR), mitral valve replacement or mitral valve repair (MVR/MVRp) with or without coronary artery bypass grafting surgery) in their institution between 1995 and 2008 (median follow-up 5.31 years, range 0.1-15.0). The authors investigated the impact of POAF on survival using multivariable Cox regression. Results Patients with POAF were older, and were more likely to have hypertension or renal failure when compared with patients without POAF. The 12-year survival in patients with POAF was 45.7+/-2.8% versus 61.4+/-2.1% in patients without POAF (p<0.001). On a multivariable analysis, when adjusting for age and other potential confounding factors, POAF tended to be associated with lower long-term survival (HR for all-cause death (HR)=1.17, 95% CI 1.00 to 1.38, p=0.051). The authors also analysed this association separately in patients with AVR and those with MVR/MVRp. In the multivariable analysis, POAF was a significant predictor of higher long-term mortality in patients with AVR (HR=1.22, CI 1.02 to 1.45, p=0.03) but not in patients with MVR/MVRp (HR=0.87, CI 0.58 to 1.29, p=0.48). Conclusions POAF is significantly associated with long term mortality following AVR but not after MVR/MVRp. The underlying factors involved in the pathogenesis of POAF after MVR/MVRp may partially account for the lack of association between POAF and survival in these patients. PMID- 22080544 TI - The diagnosis and management of pleural effusions in the ICU. AB - Pleural effusions are common in critically ill patients. Most effusions in intensive care unit (ICU) patients are of limited clinical significance; however, some are important and require aggressive management. Transudative effusions in the ICU are commonly caused by volume overload, decreased plasma oncotic pressure, and regions of altered pleural pressure attributable to atelectasis and mechanical ventilation. Exudates are sequelae of pulmonary or pleural infection, pulmonary embolism, postsurgical complications, and malignancy. Increases in pleural fluid volume are accommodated principally by chest wall expansion and, to a lesser degree, by lung collapse. Studies in mechanically ventilated patients suggest that pleural fluid drainage can result in improved oxygenation for up to 48 hours, but data on clinical outcomes are limited. Mechanically ventilated patients with pleural effusions should be semirecumbant and treated with higher levels of positive-end expiratory pressure. Rarely, large effusions can cause cardiac tamponade or tension physiology, requiring urgent drainage. Bedside ultrasound is both sensitive and specific for diagnosing pleural effusions in mechanically ventilated patients. Sonographic findings of septation and homogenous echogenicity may suggest an exudative effusion, but definitive diagnosis requires pleural fluid sampling. Thoracentesis should be carried out under ultrasound guidance. Antibiotic regimens for parapneumonic effusions should be based on current pneumonia guidelines, and anaerobic coverage should be included in the case of empyema. Decompression of the pleural space may be necessary to improve respiratory mechanics, as well as to treat complicated effusions. While small-bore catheters inserted under ultrasound guidance may be used for nonseptated effusions, surgical consultation should be sought in cases where this approach fails, or where the effusion appears complex and septated at the outset. Further research is needed to determine the effects of pleural fluid drainage on clinical outcomes in mechanically ventilated patients, to evaluate weaning strategies that include pleural fluid drainage, and to better identify patients in whom pleural effusions are more likely to be infected. PMID- 22080545 TI - Enhancing the cellular uptake of Py-Im polyamides through next-generation aryl turns. AB - Pyrrole-imidazole (Py-Im) hairpin polyamides are a class of programmable, sequence-specific DNA binding oligomers capable of disrupting protein-DNA interactions and modulating gene expression in living cells. Methods to control the cellular uptake and nuclear localization of these compounds are essential to their application as molecular probes or therapeutic agents. Here, we explore modifications of the hairpin gamma-aminobutyric acid turn unit as a means to enhance cellular uptake and biological activity. Remarkably, introduction of a simple aryl group at the turn potentiates the biological effects of a polyamide targeting the sequence 5'-WGWWCW-3' (W =A/T) by up to two orders of magnitude. Confocal microscopy and quantitative flow cytometry analysis suggest this enhanced potency is due to increased nuclear uptake. Finally, we explore the generality of this approach and find that aryl-turn modifications enhance the uptake of all polyamides tested, while having a variable effect on the upper limit of polyamide nuclear accumulation. Overall this provides a step forward for controlling the intracellular concentration of Py-Im polyamides that will prove valuable for future applications in which biological potency is essential. PMID- 22080546 TI - The International Nucleotide Sequence Database Collaboration. AB - The members of the International Nucleotide Sequence Database Collaboration (INSDC; http://www.insdc.org) set out to capture, preserve and present globally comprehensive public domain nucleotide sequence information. The work of the long standing collaboration includes the provision of data formats, annotation conventions and routine global data exchange. Among the many developments to INSDC resources in 2011 are the newly launched BioProject database and improved handling of assembly information. In this article, we outline INSDC services and update the reader on developments in 2011. PMID- 22080547 TI - Site-specific isotope labeling of long RNA for structural and mechanistic studies. AB - A site-specific isotope labeling technique of long RNA molecules was established. This technique is comprised of two simple enzymatic reactions, namely a guanosine transfer reaction of group I self-splicing introns and a ligation with T4 DNA ligase. The trans-acting group I self-splicing intron with its external cofactor, 'isotopically labeled guanosine 5'-monophosphate' (5'-GMP), steadily gave a 5' residue-labeled RNA fragment. This key reaction, in combination with a ligation of 5'-remainder non-labeled sequence, allowed us to prepare a site-specifically labeled RNA molecule in a high yield, and its production was confirmed with (15)N NMR spectroscopy. Such a site-specifically labeled RNA molecule can be used to detect a molecular interaction and to probe chemical features of catalytically/structurally important residues with NMR spectroscopy and possibly Raman spectroscopy and mass spectrometry. PMID- 22080548 TI - Major submissions tool developments at the European Nucleotide Archive. AB - The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena), Europe's primary nucleotide sequence resource, captures and presents globally comprehensive nucleic acid sequence and associated information. Covering the spectrum from raw data to assembled and functionally annotated genomes, the ENA has witnessed a dramatic growth resulting from advances in sequencing technology and ever broadening application of the methodology. During 2011, we have continued to operate and extend the broad range of ENA services. In particular, we have released major new functionality in our interactive web submission system, Webin, through developments in template-based submissions for annotated sequences and support for raw next-generation sequence read submissions. PMID- 22080549 TI - GeneWeaver: a web-based system for integrative functional genomics. AB - High-throughput genome technologies have produced a wealth of data on the association of genes and gene products to biological functions. Investigators have discovered value in combining their experimental results with published genome-wide association studies, quantitative trait locus, microarray, RNA sequencing and mutant phenotyping studies to identify gene-function associations across diverse experiments, species, conditions, behaviors or biological processes. These experimental results are typically derived from disparate data repositories, publication supplements or reconstructions from primary data stores. This leaves bench biologists with the complex and unscalable task of integrating data by identifying and gathering relevant studies, reanalyzing primary data, unifying gene identifiers and applying ad hoc computational analysis to the integrated set. The freely available GeneWeaver (http://www.GeneWeaver.org) powered by the Ontological Discovery Environment is a curated repository of genomic experimental results with an accompanying tool set for dynamic integration of these data sets, enabling users to interactively address questions about sets of biological functions and their relations to sets of genes. Thus, large numbers of independently published genomic results can be organized into new conceptual frameworks driven by the underlying, inferred biological relationships rather than a pre-existing semantic framework. An empirical 'ontology' is discovered from the aggregate of experimental knowledge around user-defined areas of biological inquiry. PMID- 22080550 TI - BYKdb: the Bacterial protein tYrosine Kinase database. AB - Bacterial tyrosine-kinases share no resemblance with their eukaryotic counterparts and they have been unified in a new protein family named BY-kinases. These enzymes have been shown to control several biological functions in the bacterial cells. In recent years biochemical studies, sequence analyses and structure resolutions allowed the deciphering of a common signature. However, BY kinase sequence annotations in primary databases remain incomplete. This prompted us to develop a specialized database of computer-annotated BY-kinase sequences: the Bacterial protein tyrosine-kinase database (BYKdb). BY-kinase sequences are first identified, thanks to a workflow developed in a previous work. A second workflow annotates the UniProtKB entries in order to provide the BYKdb entries. The database can be accessed through a web interface that allows static and dynamic queries and offers integrated sequence analysis tools. BYKdb can be found at http://bykdb.ibcp.fr. PMID- 22080551 TI - West Nile virus encodes a microRNA-like small RNA in the 3' untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells. AB - West Nile virus (WNV) belongs to a group of medically important single-stranded, positive-sense RNA viruses causing deadly disease outbreaks around the world. The 3' untranslated region (3'-UTR) of the flavivirus genome, in particular the terminal 3' stem-loop (3'SL) fulfils multiple functions in virus replication and virus-host interactions. Using the Kunjin strain of WNV (WNV(KUN)), we detected a virally encoded small RNA, named KUN-miR-1, derived from 3'SL. Transcription of WNV(KUN) pre-miRNA (3'SL) in mosquito cells either from plasmid or Semliki Forest virus (SFV) RNA replicon resulted in the production of mature KUN-miR-1. Silencing of Dicer-1 but not Dicer-2 led to a reduction in the miRNA levels. Further, when a synthetic inhibitor of KUN-miR-1 was transfected into mosquito cells, replication of viral RNA was significantly reduced. Using cloning and bioinformatics approaches, we identified the cellular GATA4 mRNA as a target for KUN-miR-1. KUN-miR-1 produced in mosquito cells during virus infection or from plasmid DNA, SFV RNA replicon or mature miRNA duplex increased accumulation of GATA4 mRNA. Depletion of GATA4 mRNA by RNA silencing led to a significant reduction in virus RNA replication while a KUN-miR-1 RNA mimic enhanced replication of a mutant WNV(KUN) virus producing reduced amounts of KUN-miR-1, suggesting that GATA4-induction via KUN-miR-1 plays an important role in virus replication. PMID- 22080552 TI - Nonspaced inverted DNA repeats are preferential targets for homology-directed gene repair in mammalian cells. AB - DNA repeats constitute potential sites for the nucleation of secondary structures such as hairpins and cruciforms. Studies performed mostly in bacteria and yeast showed that these noncanonical DNA structures are breakage-prone, making them candidate targets for cellular DNA repair pathways. Possible culprits for fragility at repetitive DNA sequences include replication and transcription as well as the action of structure-specific nucleases. Despite their patent biological relevance, the parameters governing DNA repeat-associated chromosomal transactions remain ill-defined. Here, we established an episomal recombination system based on donor and acceptor complementary DNA templates to investigate the role of direct and inverted DNA repeats in homologous recombination (HR) in mammalian cells. This system allowed us also to ascertain in a stringent manner the impact of repetitive sequence replication on homology-directed gene repair. We found that nonspaced DNA repeats can, per se, engage the HR pathway of the cell and that this process is primarily dependent on their spacing and relative arrangement (i.e. parallel or antiparallel) rather than on their sequence. Indeed, our data demonstrate that contrary to direct and spaced inverted repeats, nonspaced inverted repeats are intrinsically recombinogenic motifs in mammalian cells lending experimental support to their role in genome dynamics in higher eukaryotes. PMID- 22080553 TI - Pocketome: an encyclopedia of small-molecule binding sites in 4D. AB - The importance of binding site plasticity in protein-ligand interactions is well recognized, and so are the difficulties in predicting the nature and the degree of this plasticity by computational means. To assist in understanding the flexible protein-ligand interactions, we constructed the Pocketome, an encyclopedia of about one thousand experimentally solved conformational ensembles of druggable binding sites in proteins, grouped by location and consistent chain/cofactor composition. The multiplicity of pockets within the ensembles adds an extra, fourth dimension to the Pocketome entry data. Within each ensemble, the pockets were carefully classified by the degree of their pairwise similarity and compatibility with different ligands. The core of the Pocketome is derived regularly and automatically from the current releases of the Protein Data Bank and the Uniprot Knowledgebase; this core is complemented by entries built from manually provided seed ligand locations. The Pocketome website (www.pocketome.org) allows searching for the sites of interest, analysis of conformational clusters, important residues, binding compatibility matrices and interactive visualization of the ensembles using the ActiveICM web browser plugin. The Pocketome collection can be used to build multi-conformational docking and 3D activity models as well as to design cross-docking and virtual ligand screening benchmarks. PMID- 22080554 TI - Disease Ontology: a backbone for disease semantic integration. AB - The Disease Ontology (DO) database (http://disease-ontology.org) represents a comprehensive knowledge base of 8043 inherited, developmental and acquired human diseases (DO version 3, revision 2510). The DO web browser has been designed for speed, efficiency and robustness through the use of a graph database. Full-text contextual searching functionality using Lucene allows the querying of name, synonym, definition, DOID and cross-reference (xrefs) with complex Boolean search strings. The DO semantically integrates disease and medical vocabularies through extensive cross mapping and integration of MeSH, ICD, NCI's thesaurus, SNOMED CT and OMIM disease-specific terms and identifiers. The DO is utilized for disease annotation by major biomedical databases (e.g. Array Express, NIF, IEDB), as a standard representation of human disease in biomedical ontologies (e.g. IDO, Cell line ontology, NIFSTD ontology, Experimental Factor Ontology, Influenza Ontology), and as an ontological cross mappings resource between DO, MeSH and OMIM (e.g. GeneWiki). The DO project (http://diseaseontology.sf.net) has been incorporated into open source tools (e.g. Gene Answers, FunDO) to connect gene and disease biomedical data through the lens of human disease. The next iteration of the DO web browser will integrate DO's extended relations and logical definition representation along with these biomedical resource cross-mappings. PMID- 22080555 TI - The UCSC Archaeal Genome Browser: 2012 update. AB - The UCSC Archaeal Genome Browser (http://archaea.ucsc.edu) offers a graphical web based resource for exploration and discovery within archaeal and other selected microbial genomes. By bringing together existing gene annotations, gene expression data, multiple-genome alignments, pre-computed sequence comparisons and other specialized analysis tracks, the genome browser is a powerful aggregator of varied genomic information. The genome browser environment maintains the current look-and-feel of the vertebrate UCSC Genome Browser, but also integrates archaeal and bacterial-specific tracks with a few graphic display enhancements. The browser currently contains 115 archaeal genomes, plus 31 genomes of viruses known to infect archaea. Some of the recently developed or enhanced tracks visualize data from published high-throughput RNA-sequencing studies, the NCBI Conserved Domain Database, sequences from pre-genome sequencing studies, predicted gene boundaries from three different protein gene prediction algorithms, tRNAscan-SE gene predictions with RNA secondary structures and CRISPR locus predictions. We have also developed a companion resource, the Archaeal COG Browser, to provide better search and display of arCOG gene function classifications, including their phylogenetic distribution among available archaeal genomes. PMID- 22080556 TI - CoryneRegNet 6.0--Updated database content, new analysis methods and novel features focusing on community demands. AB - Post-genomic analysis techniques such as next-generation sequencing have produced vast amounts of data about micro organisms including genetic sequences, their functional annotations and gene regulatory interactions. The latter are genetic mechanisms that control a cell's characteristics, for instance, pathogenicity as well as survival and reproduction strategies. CoryneRegNet is the reference database and analysis platform for corynebacterial gene regulatory networks. In this article we introduce the updated version 6.0 of CoryneRegNet and describe the updated database content which includes, 6352 corynebacterial regulatory interactions compared with 4928 interactions in release 5.0 and 3235 regulations in release 4.0, respectively. We also demonstrate how we support the community by integrating analysis and visualization features for transiently imported custom data, such as gene regulatory interactions. Furthermore, with release 6.0, we provide easy-to-use functions that allow the user to submit data for persistent storage with the CoryneRegNet database. Thus, it offers important options to its users in terms of community demands. CoryneRegNet is publicly available at http://www.coryneregnet.de. PMID- 22080557 TI - Genome-wide transcriptome analysis of the plant pathogen Xanthomonas identifies sRNAs with putative virulence functions. AB - The Gram-negative plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria (Xcv) is an important model to elucidate the mechanisms involved in the interaction with the host. To gain insight into the transcriptome of the Xcv strain 85-10, we took a differential RNA sequencing (dRNA-seq) approach. Using a novel method to automatically generate comprehensive transcription start site (TSS) maps we report 1421 putative TSSs in the Xcv genome. Genes in Xcv exhibit a poorly conserved -10 promoter element and no consensus Shine-Dalgarno sequence. Moreover, 14% of all mRNAs are leaderless and 13% of them have unusually long 5' UTRs. Northern blot analyses confirmed 16 intergenic small RNAs and seven cis encoded antisense RNAs in Xcv. Expression of eight intergenic transcripts was controlled by HrpG and HrpX, key regulators of the Xcv type III secretion system. More detailed characterization identified sX12 as a small RNA that controls virulence of Xcv by affecting the interaction of the pathogen and its host plants. The transcriptional landscape of Xcv is unexpectedly complex, featuring abundant antisense transcripts, alternative TSSs and clade-specific small RNAs. PMID- 22080558 TI - HotRegion: a database of predicted hot spot clusters. AB - Hot spots are energetically important residues at protein interfaces and they are not randomly distributed across the interface but rather clustered. These clustered hot spots form hot regions. Hot regions are important for the stability of protein complexes, as well as providing specificity to binding sites. We propose a database called HotRegion, which provides the hot region information of the interfaces by using predicted hot spot residues, and structural properties of these interface residues such as pair potentials of interface residues, accessible surface area (ASA) and relative ASA values of interface residues of both monomer and complex forms of proteins. Also, the 3D visualization of the interface and interactions among hot spot residues are provided. HotRegion is accessible at http://prism.ccbb.ku.edu.tr/hotregion. PMID- 22080559 TI - The Aspergillus Genome Database (AspGD): recent developments in comprehensive multispecies curation, comparative genomics and community resources. AB - The Aspergillus Genome Database (AspGD; http://www.aspgd.org) is a freely available, web-based resource for researchers studying fungi of the genus Aspergillus, which includes organisms of clinical, agricultural and industrial importance. AspGD curators have now completed comprehensive review of the entire published literature about Aspergillus nidulans and Aspergillus fumigatus, and this annotation is provided with streamlined, ortholog-based navigation of the multispecies information. AspGD facilitates comparative genomics by providing a full-featured genomics viewer, as well as matched and standardized sets of genomic information for the sequenced aspergilli. AspGD also provides resources to foster interaction and dissemination of community information and resources. We welcome and encourage feedback at aspergillus-curator@lists.stanford.edu. PMID- 22080560 TI - MIPModDB: a central resource for the superfamily of major intrinsic proteins. AB - The channel proteins belonging to the major intrinsic proteins (MIP) superfamily are diverse and are found in all forms of life. Water-transporting aquaporin and glycerol-specific aquaglyceroporin are the prototype members of the MIP superfamily. MIPs have also been shown to transport other neutral molecules and gases across the membrane. They have internal homology and possess conserved sequence motifs. By analyzing a large number of publicly available genome sequences, we have identified more than 1000 MIPs from diverse organisms. We have developed a database MIPModDB which will be a unified resource for all MIPs. For each MIP entry, this database contains information about the source, gene structure, sequence features, substitutions in the conserved NPA motifs, structural model, the residues forming the selectivity filter and channel radius profile. For selected set of MIPs, it is possible to derive structure-based sequence alignment and evolutionary relationship. Sequences and structures of selected MIPs can be downloaded from MIPModDB database which is freely available at http://bioinfo.iitk.ac.in/MIPModDB. PMID- 22080562 TI - Network of Cancer Genes (NCG 3.0): integration and analysis of genetic and network properties of cancer genes. AB - The identification of a constantly increasing number of genes whose mutations are causally implicated in tumor initiation and progression (cancer genes) requires the development of tools to store and analyze them. The Network of Cancer Genes (NCG 3.0) collects information on 1494 cancer genes that have been found mutated in 16 different cancer types. These genes were collected from the Cancer Gene Census as well as from 18 whole exome and 11 whole-genome screenings of cancer samples. For each cancer gene, NCG 3.0 provides a summary of the gene features and the cross-reference to other databases. In addition, it describes duplicability, evolutionary origin, orthology, network properties, interaction partners, microRNA regulation and functional roles of cancer genes and of all genes that are related to them. This integrated network of information can be used to better characterize cancer genes in the context of the system in which they act. The data can also be used to identify novel candidates that share the same properties of known cancer genes and may therefore play a similar role in cancer. NCG 3.0 is freely available at http://bio.ifom-ieo-campus.it/ncg. PMID- 22080563 TI - CADRE: the Central Aspergillus Data REpository 2012. AB - The Central Aspergillus Data REpository (CADRE; http://www.cadre-genomes.org.uk) is a public resource for genomic data extracted from species of Aspergillus. It provides an array of online tools for searching and visualising features of this significant fungal genus. CADRE arose from a need within the medical community to understand the human pathogen Aspergillus fumigatus. Due to the paucity of Aspergillus genomic resources 10 years ago, the long-term goal of this project was to collate and maintain Aspergillus genomes as they became available. Since our first release in 2004, the resource has expanded to encompass annotated sequence for eight other Aspergilli and provides much needed support to the international Aspergillus research community. Recent developments, however, in sequencing technology are creating a vast amount of genomic data and, as a result, we shortly expect a tidal wave of Aspergillus data. In preparation for this, we have upgraded the database and software suite. This not only enables better management of more complex data sets, but also improves annotation by providing access to genome comparison data and the integration of high-throughput data. PMID- 22080564 TI - AnimalTFDB: a comprehensive animal transcription factor database. AB - Transcription factors (TFs) are proteins that bind to specific DNA sequences, thereby playing crucial roles in gene-expression regulation through controlling the transcription of genetic information from DNA to RNA. Transcription cofactors and chromatin remodeling factors are also essential in the gene transcriptional regulation. Identifying and annotating all the TFs are primary and crucial steps for illustrating their functions and understanding the transcriptional regulation. In this study, based on manual literature reviews, we collected and curated 72 TF families for animals, which is currently the most complete list of TF families in animals. Then, we systematically characterized all the TFs in 50 animal species and constructed a comprehensive animal TF database, AnimalTFDB. To better serve the community, we provided detailed annotations for each TF, including basic information, gene structure, functional domain, 3D structure hit, Gene Ontology, pathway, protein-protein interaction, paralogs, orthologs, potential TF-binding sites and targets. In addition, we collected and annotated transcription cofactors and chromatin remodeling factors. AnimalTFDB has a user friendly web interface with multiple browse and search functions, as well as data downloading. It is freely available at http://www.bioguo.org/AnimalTFDB/. PMID- 22080561 TI - GABI-Kat SimpleSearch: new features of the Arabidopsis thaliana T-DNA mutant database. AB - T-DNA insertion mutants are very valuable for reverse genetics in Arabidopsis thaliana. Several projects have generated large sequence-indexed collections of T DNA insertion lines, of which GABI-Kat is the second largest resource worldwide. User access to the collection and its Flanking Sequence Tags (FSTs) is provided by the front end SimpleSearch (http://www.GABI-Kat.de). Several significant improvements have been implemented recently. The database now relies on the TAIRv10 genome sequence and annotation dataset. All FSTs have been newly mapped using an optimized procedure that leads to improved accuracy of insertion site predictions. A fraction of the collection with weak FST yield was re-analysed by generating new FSTs. Along with newly found predictions for older sequences about 20,000 new FSTs were included in the database. Information about groups of FSTs pointing to the same insertion site that is found in several lines but is real only in a single line are included, and many problematic FST-to-line links have been corrected using new wet-lab data. SimpleSearch currently contains data from ~71,000 lines with predicted insertions covering 62.5% of the 27,206 nuclear protein coding genes, and offers insertion allele-specific data from 9545 confirmed lines that are available from the Nottingham Arabidopsis Stock Centre. PMID- 22080565 TI - modMine: flexible access to modENCODE data. AB - In an effort to comprehensively characterize the functional elements within the genomes of the important model organisms Drosophila melanogaster and Caenorhabditis elegans, the NHGRI model organism Encyclopaedia of DNA Elements (modENCODE) consortium has generated an enormous library of genomic data along with detailed, structured information on all aspects of the experiments. The modMine database (http://intermine.modencode.org) described here has been built by the modENCODE Data Coordination Center to allow the broader research community to (i) search for and download data sets of interest among the thousands generated by modENCODE; (ii) access the data in an integrated form together with non-modENCODE data sets; and (iii) facilitate fine-grained analysis of the above data. The sophisticated search features are possible because of the collection of extensive experimental metadata by the consortium. Interfaces are provided to allow both biologists and bioinformaticians to exploit these rich modENCODE data sets now available via modMine. PMID- 22080566 TI - Metastasis suppressor NM23-H1 promotes repair of UV-induced DNA damage and suppresses UV-induced melanomagenesis. AB - Reduced expression of the metastasis suppressor NM23-H1 is associated with aggressive forms of multiple cancers. Here, we establish that NM23-H1 (termed H1 isoform in human, M1 in mouse) and two of its attendant enzymatic activities, the 3'-5' exonuclease and nucleoside diphosphate kinase, are novel participants in the cellular response to UV radiation (UVR)-induced DNA damage. NM23-H1 deficiency compromised the kinetics of repair for total DNA polymerase-blocking lesions and nucleotide excision repair of (6-4) photoproducts in vitro. Kinase activity of NM23-H1 was critical for rapid repair of both polychromatic UVB/UVA induced (290-400 nm) and UVC-induced (254 nm) DNA damage, whereas its 3'-5' exonuclease activity was dominant in the suppression of UVR-induced mutagenesis. Consistent with its role in DNA repair, NM23-H1 rapidly translocated to sites of UVR-induced (6-4) photoproduct DNA damage in the nucleus. In addition, transgenic mice hemizygous-null for nm23-m1 and nm23-m2 exhibited UVR-induced melanoma and follicular infundibular cyst formation, and tumor-associated melanocytes displayed invasion into adjacent dermis, consistent with loss of invasion suppressing activity of NM23 in vivo. Taken together, our data show a critical role for NM23 isoforms in limiting mutagenesis and suppressing UVR-induced melanomagenesis. PMID- 22080567 TI - Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer. AB - Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance ((1)H-NMR) to profile the serum metabolome in patients with mCRC and determine whether a disease signature may exist that is strong enough to predict overall survival (OS). In 153 patients with mCRC and 139 healthy subjects from three Danish hospitals, we profiled two independent sets of serum samples in a prospective phase II study. In the training set, (1)H-NMR metabolomic profiling could discriminate patients with mCRC from healthy subjects with a cross-validated accuracy of 100%. In the validation set, 96.7% of subjects were correctly classified. Patients from the training set with maximally divergent OS were chosen to construct an OS predictor. After validation, patients predicted to have short OS had significantly reduced survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 * 10(-6)). A number of metabolites concurred with the (1)H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that (1)H-NMR profiling of patient serum can provide a strong metabolomic signature of mCRC and that analysis of this signature may offer an independent tool to predict OS. PMID- 22080568 TI - Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. AB - Activation of the EGFR, KRAS, and ALK oncogenes defines 3 different pathways of molecular pathogenesis in lung adenocarcinoma. However, many tumors lack activation of any pathway (triple-negative lung adenocarcinomas) posing a challenge for prognosis and treatment. Here, we report an extensive genome-wide expression profiling of 226 primary human stage I-II lung adenocarcinomas that elucidates molecular characteristics of tumors that harbor ALK mutations or that lack EGFR, KRAS, and ALK mutations, that is, triple-negative adenocarcinomas. One hundred and seventy-four genes were selected as being upregulated specifically in 79 lung adenocarcinomas without EGFR and KRAS mutations. Unsupervised clustering using a 174-gene signature, including ALK itself, classified these 2 groups of tumors into ALK-positive cases and 2 distinct groups of triple-negative cases (groups A and B). Notably, group A triple-negative cases had a worse prognosis for relapse and death, compared with cases with EGFR, KRAS, or ALK mutations or group B triple-negative cases. In ALK-positive tumors, 30 genes, including ALK and GRIN2A, were commonly overexpressed, whereas in group A triple-negative cases, 9 genes were commonly overexpressed, including a candidate diagnostic/therapeutic target DEPDC1, that were determined to be critical for predicting a worse prognosis. Our findings are important because they provide a molecular basis of ALK-positive lung adenocarcinomas and triple-negative lung adenocarcinomas and further stratify more or less aggressive subgroups of triple negative lung ADC, possibly helping identify patients who may gain the most benefit from adjuvant chemotherapy after surgical resection. PMID- 22080569 TI - Contrasting behavior of the p18INK4c and p16INK4a tumor suppressors in both replicative and oncogene-induced senescence. AB - The cyclin-dependent kinase (CDK) inhibitors, p18(INK4c) and p16(INK4a), both have the credentials of tumor suppressors in human cancers and mouse models. For p16(INK4a), the underlying rationale is its role in senescence, but the selective force for inactivation of p18(INK4c) in incipient cancer cells is less clear. Here, we show that in human fibroblasts undergoing replicative or oncogene induced senescence, there is a marked decline in the levels of p18(INK4c) protein and RNA, which mirrors the accumulation of p16(INK4a). Downregulation of INK4c is not dependent on p16(INK4a), and RAS can promote the loss of INK4c without cell cycle arrest. Downregulation of p18(INK4c) correlates with reduced expression of menin and E2F1 but is unaffected by acute cell-cycle arrest or inactivation of the retinoblastoma protein (pRb). Collectively, our data question the idea that p18(INK4c) acts as a backup for loss of p16(INK4a) and suggest that the apparent activation of p18(INK4c) in some settings represents delayed senescence rather than increased expression. We propose that the contrasting behavior of the two very similar INK4 proteins could reflect their respective roles in senescence versus differentiation. PMID- 22080570 TI - Pim kinase inhibitors sensitize prostate cancer cells to apoptosis triggered by Bcl-2 family inhibitor ABT-737. AB - Pim serine/threonine kinases contribute to prostate tumorigenesis and therapeutic resistance, yet Pim kinase inhibitors seem to have only limited effects on prostate cancer cell survival. Because overexpression of Bcl-2 family members are implicated in chemotherapeutic resistance in prostate cancer, we investigated the cooperative effects of Pim kinase inhibition with ABT-737, a small molecule antagonist of Bcl-2 family members. Strikingly, the addition of ABT-737 to Pim inhibitors triggered a robust apoptosis of prostate cancer cells in vitro and in vivo. Pim inhibitors decreased levels of the Bcl-2 family member Mcl-1, both by blocking 5'-cap dependent translation and decreasing protein half life. In addition, Pim inhibition transcriptionally increased levels of the BH3 protein Noxa by activating the unfolded protein response (UPR), lead to eIF-2alpha phosphorylation and increased expression of CHOP. Increased levels of Noxa also inactivated the remaining levels of Mcl-1 protein activity. Notably, these specific protein changes were essential to the apoptotic process because ABT-737 did not inhibit Mcl-1 protein activity and Mcl-1 overexpression blocked the apoptotic activity of ABT-737. Our results therefore suggest that this combination treatment could be developed as a potential therapy for human prostate cancer where overexpression of Pim kinases and antiapoptotic Bcl-2 family members drives tumor cell resistance to current anticancer therapies. PMID- 22080572 TI - Butyrate delivered by butyrylated starch increases distal colonic epithelial apoptosis in carcinogen-treated rats. AB - Animal studies show that increasing large bowel butyrate concentration through ingestion of butyrylated or resistant starches opposes carcinogen-induced tumorigenesis, which is consistent with population data linking greater fiber consumption with lowered colorectal cancer (CRC) risk. Butyrate has been shown to regulate the apoptotic response to DNA damage. This study examined the impact of increasing large bowel butyrate concentration by dietary butyrylated starch on the colonic epithelium of rats treated with the genotoxic carcinogen azoxymethane (AOM). Four groups of 10 male rats were fed AIN-93G based-diets containing either low amylose maize starch (LAMS), LAMS with 3% tributyrin, 10% high amylose maize starch (HAMS) or 10% butyrylated HAMS (HAMSB). HAMS and HAMSB starches were cooked by heating in water. After 4 weeks, rats were injected once with AOM and killed 6 h later. Rates of apoptosis and proliferation were measured in colonic epithelium. Short-chain fatty acid concentrations in large bowel digesta and hepatic portal venous plasma were higher in HAMSB than all other groups. Apoptotic rates in the distal colon were increased by HAMSB and correlated with luminal butyrate concentrations but cellular proliferation rates were unaffected by diet. The increase in apoptosis was most marked in the base and proliferative zone of the crypt. Regulation of luminal butyrate using HAMSB increases the rates of apoptotic deletion of DNA-damaged colonocytes. We propose this pro-apoptotic function of butyrate plays a major role reducing tumour formation in the AOM treated rat and that these data support a potential protective role of butyrate in CRC. PMID- 22080571 TI - The molecular basis that unifies the metabolism, cellular uptake and chemopreventive activities of dietary isothiocyanates. AB - Organic isothiocyanates (ITCs), which are characterized by the presence of an N=C=S group, are among the most extensively studied cancer chemopreventive agents and show highly promising chemopreventive activities. Numerous studies have shown that ITCs can inhibit both carcinogenesis and cancer growth in a variety of animal models. Many cruciferous vegetables, which are commonly consumed by humans, are rich sources of these compounds. Of particular interest are their high bioavailability, their shared metabolic profile and their ability to target a wide array of cancer-related cellular proteins. This review is focused on discussing the molecular basis of these intriguing properties of ITCs, with a particular emphasis on the concept that cellular uptake and metabolism of ITCs and at least some of their major chemopreventive activities are all initiated through direct reaction of the carbon atom of the -N=C=S group of the ITCs with cysteine sulfhydryl groups of glutathione (GSH) and of proteins. This knowledge deepens our understanding about the biological activities of ITCs and may facilitate further research and development of these compounds for cancer prevention and treatment. PMID- 22080573 TI - Lignan transformation by gut bacteria lowers tumor burden in a gnotobiotic rat model of breast cancer. AB - High dietary lignan exposure is implicated in a reduced breast cancer risk in women. The bacterial transformation of plant lignans to enterolignans is thought to be essential for this effect. To provide evidence for this assumption, gnotobiotic rats were colonized with the lignan-converting bacteria Clostridium saccharogumia, Eggerthella lenta, Blautia producta and Lactonifactor longoviformis (LCC rats). Germ-free rats were used as the control. All animals were fed a lignan-rich flaxseed diet and breast cancer was induced with 7,12 dimethylbenz(a)anthracene. The lignan secoisolariciresinol diglucoside was converted into the enterolignans enterodiol and enterolactone in the LCC but not in the germ-free rats. This transformation did not influence cancer incidence at the end of the 13 weeks experimental period but significantly decreased tumor numbers per tumor-bearing rat, tumor size, tumor cell proliferation and increased tumor cell apoptosis in LCC rats. No differences between LCC and control rats were observed in the expression of the genes encoding the estrogen receptors (ERs) alpha, ERbeta and G-coupled protein 30. The same was true for IGF-1 and EGFR involved in tumor growth. The activity of selected enzymes involved in the degradation of oxidants in plasma and liver was significantly increased in the LCC rats. However, plasma and liver concentrations of reduced glutathione and malondialdehyde, considered as oxidative stress markers, did not differ between the groups. In conclusion, our results show that the bacterial conversion of plant lignans to enterolignans beneficially influences their anticancer effects. PMID- 22080574 TI - The relationship between marijuana use and intimate partner violence in a nationally representative, longitudinal sample. AB - Intimate partner violence is a significant public health problem, as these behaviors have been associated with a number of negative health outcomes including illicit drug use, physical injury, chronic pain, sexually transmitted diseases, depression, and posttraumatic stress disorder. The current study examined the association between marijuana use and intimate partner violence using a longitudinal survey of adolescents and young adults ages 15 to 26 years. Data were obtained from 9,421 adolescents in the National Longitudinal Study of Adolescent Health (Add Health) Waves 1 through 4 (1995-2008). Marijuana use was measured in the past year at each wave and participants were categorized as "users" or "nonusers." Partner violence was constructed using six items (three pertaining to victimization and three concerning perpetration) from Wave 4 (2007 2008). Using these six items, participants were categorized as "victims only," "perpetrators only," or "victims and perpetrators." Survey multinomial regression was used to examine the relationship between marijuana use and intimate partner violence. Consistent use of marijuana during adolescence was most predictive of intimate partner violence (OR = 2.08, p < .001). Consistent marijuana use (OR = 1.85, p < .05) was related to an increased risk of intimate partner violence perpetration. Adolescent marijuana use, particularly consistent use throughout adolescence, is associated with perpetration or both perpetration of and victimization by intimate partner violence in early adulthood. These findings have implications for intimate partner violence prevention efforts, as marijuana use should be considered as a target of early intimate partner violence intervention and treatment programming. PMID- 22080575 TI - What would they do? Latino church leaders and domestic violence. AB - Understanding what Latino church leaders believe about domestic violence, and what they do when they confront it, is a key step in developing programs to help them engage in domestic violence prevention and intervention activities in their congregations. This article presents the findings from an exploratory study of 28 Latino church leaders. The study surveyed respondents' beliefs about domestic violence and asked for their reactions to three domestic violence vignettes they might encounter. We found that study participants were willing to respond to cases of domestic violence in what we would define as constructive ways. However, some responses suggested potentially unsafe and ill-advised reactions to the vignettes. We discuss our study's implications for practice and suggest future directions for additional research. PMID- 22080576 TI - Translating sexual assault prevention from a college campus to a United States military installation: piloting the know-your-power bystander social marketing campaign. AB - One population that shares both similar and different characteristics with traditional college-age students is the U.S. Military. Similarities include a high concentration of 18- to 26-year-olds dealing with new found independence, peer pressure, and the presence of social norms that support violence and hypermasculinity. Sexual violence is a major public health problem in the United States, and because of the similarities in the age group of college and military populations, the problems regarding sexual violence in both constituencies have been well-documented. In the current pilot study we seek to add to both current knowledge about and promising practices of translating prevention strategies from one target audience to another. We describe how we translated, administered, and evaluated a bystander intervention social marketing campaign focused on sexual assault prevention that had been found to significantly affect attitude change on a college campus for a U.S. Army installation in Europe. In addition to demonstrating the process of translating prevention strategies across target audiences, findings from this pilot study contribute to the evaluation data on the effectiveness of sexual violence prevention strategies implemented with members of the U.S. Military. From our analysis, we see that research participants indicate that the degree to which the images resonate with them and the familiarity of the context (i.e., social self-identification) significantly effect the participants' personal responsibility for reducing sexual assault, confidence in acting as a bystander, and reported engagement as a bystander. PMID- 22080577 TI - Gender-specific risk factors for intimate partner homicide--a nationwide register based study. AB - The present study examined gender differences in intimate partner homicide (IPH) and offender characteristics with the focus on putative gender-specific risk factors in a nationwide consecutive sample of homicide offenders. Data on all offenders (N = 642; 91 females, 551 males) convicted of homicide and subjected to a forensic psychiatric examination in Finland were obtained for the years 1995 and 2004. IPH offenders, 39 female and 106 male, were compared for risk factors with female and male offenders whose victims were not spouses. The forensic psychiatric examination reports were retrospectively analyzed, and the Hare Psychopathy Checklist-Revised (PCL-R) was rated. Significant gender differences were found in four risk factors: employment, intoxication of victim, self defense, and quarrel, mostly related to alcohol as a factor of the offense. The findings support the notion that female IPH is linked to defensive reactions resulting from prior abuse, and that IPH offenders resemble the general population more than offenders of other types of homicide. PMID- 22080578 TI - The mediating role of self-regulation between intrafamilial violence and mental health adjustment in incarcerated male adolescents. AB - This article investigates the relation between history of intrafamilial violence and self-regulatory capacity, cognitive processing, and mental health adjustment in incarcerated adolescents. Adolescents were incarcerated at the time of the study for various violent offenses, ranging from persistent delinquency to sexual assault (n = 115). A model is proposed that posits that self-regulation, cognitive ability, and cognitive processing are integral to the relation between intrafamilial violence and mental health function. The primary hypothesis of the study tests this mediation model. The relations between mental health, cognitive processing, self-regulation, and intrafamilial violence are also examined. The study was conducted during two sessions at a juvenile facility in the Midwest using survey measures, academic and intelligence testing, and cognitive tasks. Youth were between the ages of 13 and 20. Approximately 70% were previously diagnosed with a disability. Significant Pearson's correlations were found between seven out of eight mental health subscales of the Youth Self-Report (YSR) and intrafamilial violence history. Structural equation modeling was used to examine the role of cognitive processing in the association between intrafamilial violence and mental health function. Nonverbal or performance deficits, a significant difference between verbal skills and nonverbal skills, were related to intrafamilial violence. Self-regulation partially mediated the relation between intrafamilial violence and mental health function. Self-regulation ability may be compromised by intrafamilial violence and be a precursor to both internalizing and externalizing mental health problem in incarcerated youth. Educational, clinical, and research implications are discussed. PMID- 22080579 TI - Domestic violence during pregnancy in an eastern city of Turkey: a field study. AB - Violence is an increasing and important community health problem that can be seen in any area of human life. Limited studies were found about domestic violence among pregnant women and its relation with social status of women. The aim of this study was to determine the prevalence and types of domestic violence during pregnancy, factors affecting it, women's thoughts about violence, and relation between social status of women and domestic violence. This cross-sectional study was conducted on 253 pregnant women, using cluster and simple random sampling methods. Chi-square test and logistic regression analysis methods were used to analyze the data. Women who indicated that they have been exposed to violence at some point of their lives were 24.1% and who indicated that violence continued while they were pregnant were 11.1%. Physical violence was the most common type of violence reported (18.2%). It was found that women who had primary school or lower level of education and who made unwanted marriage suffered from more violence during pregnancy. It can be said that violence against pregnant women is still a social problem. In societies where gender roles are dominant, decision makers have to take necessary steps such as supporting education of girls to improve social status of women, increasing awareness among women in regard to personal rights and legal regulations which will contribute to the solution of the issue. PMID- 22080580 TI - Service providers' reactions to intimate partner violence as a function of victim sexual orientation and type of abuse. AB - In this online vignette study, a national sample of domestic violence shelter service providers (N = 282) completed a 10-item questionnaire about a woman experiencing intimate partner violence (IPV). Scenarios varied in terms of couple sexual orientation (heterosexual or lesbian) and type of abuse (physical or nonphysical). Results indicate that although participants did not overtly discriminate against a woman in a lesbian relationship, they were less likely to perceive her as a victim, and their acceptance of a lesbian as a client was more dependent on their comfort with her than was the case for a woman in a heterosexual relationship. Type of abuse, as expected, had a main effect on many questions, with physical abuse taken more seriously than nonphysical abuse. Scores on the Attitudes Toward Lesbians subscale (Herek) were unrelated to responses. Implications for service providers are discussed. PMID- 22080581 TI - Poor parenting and antisocial behavior among homeless young adults: links to dating violence perpetration and victimization. AB - Though research has examined risk factors associated with street victimization among homeless young people, little is known about dating violence experiences among this group. Given homeless youths' elevated rates of child maltreatment, it is likely that they are at high risk for dating violence. As such, the current study examined the association between child maltreatment and parental warmth with dating violence perpetration and victimization through substance use and delinquency among a sample of 172 homeless males and females. Results from path analysis revealed that physical abuse, sexual abuse, and neglect were all significant correlates of both substance use and delinquency, whereas lack of parental warmth was only associated with substance use. Neglect and substance use had direct effects on dating violence and substance use and was found to mediate the relationship between physical abuse and dating violence. Finally, females, older youth, and non-Whites had significantly higher levels of dating violence compared with their counterparts. PMID- 22080582 TI - The effect of offenders' sex on reporting crimes to the police. AB - This article examines the difference in victims' reporting behavior regarding crimes committed by males and by females. The authors expect that victims of female offenders are less likely to report to the police than victims of male offenders because of differences in the victim-offender relationship as well as in the victim's sex. With recent developments in Bayesian statistics, new tools have become available that enable the direct evaluation of researchers' expectations. All cases of robbery with assault from the National Crime Victimization Survey have been investigated (n = 478). Findings reveal that female offenders are underreported compared with male offenders and that this can be explained by the victim characteristics but only in combination with the offender's sex. PMID- 22080583 TI - Predictors of sexual aggression among male juvenile offenders. AB - The purpose of this study was to conduct a longitudinal examination of predictors of sexual aggression among male juvenile offenders. Four hundred and four adolescent males between the ages of 14 and 17 years were recruited from juvenile probation offices to take part in a prospective study of substance use and sexual risk. At baseline, participants completed a series of questionnaires that assessed putative risk factors for sexual aggression. They then completed a measure of sexual aggression at the 6-month follow-up period. Correlational analyses revealed that participants who reported hard drug use, more frequent alcohol and marijuana use, and less severe offenses reported engaging in more severe sexual aggression. In addition, participants who reported higher impulsivity, sensation seeking, and externalizing behaviors also reported participating in more severe sexual aggression. When these variables were included in a regression analysis, only externalizing behaviors and severity of offense uniquely predicted severity of sexual aggression at the 6-month follow up. PMID- 22080584 TI - Individual and contextual factors associated to smoking on school premises. AB - INTRODUCTION: Despite regulations, tobacco consumption in schools is still very common. The objective was to evaluate the relationship of personal, family, and school-level contextual factors with smoking on school premises. METHODS: A representative survey was undertaken of students in the 4th year of secondary education in the Madrid region (Spain), including 79 schools and 3,622 individuals. The student questionnaire gathered information about personal and family variables. The contextual factors were type of school, perception of compliance with the law, smoking policy, existence of complaints against smoking, and undertaking of educational activities regarding smoking. Analysis was carried out in the smoking population (n = 1,179) using multilevel logistic regression models. RESULTS: During the last 30 days, 50.6% of smokers had smoked on school premises. Having a father with a university education (in comparison with fathers who have not attained any educational level) reduces this probability (odds ratio [OR]: 0.43; 95% CI: 0.19-0.96), whereas smoking a larger number of cigarettes (p < .001), illicit drug consumption (p < .001), and low academic achievement (p = .052) increases it. The probability is reduced when there is no parental permission to smoke (OR: 0.66; 95% CI: 0.43-1.01) and is lower both in nonsubsidized private schools (OR: 0.29; 95% CI: 0.12-0.67) and in state subsidized private schools (OR: 0.17; 95% CI: 0.09-0.34) than in public schools. CONCLUSIONS: A very low level of educational attainment by the father, smoking a higher number of cigarettes, as well as illicit drug consumption, low academic achievement, having parental permission to smoke, and attending public schools are all related to a higher probability of smoking on school premises. PMID- 22080585 TI - Portrayal of smokeless tobacco in YouTube videos. AB - OBJECTIVES: Videos of smokeless tobacco (ST) on YouTube are abundant and easily accessible, yet no studies have examined the content of ST videos. This study assesses the overall portrayal, genre, and messages of ST YouTube videos. METHODS: In August 2010, researchers identified the top 20 search results on YouTube by "relevance" and "view count" for the following search terms: "ST," "chewing tobacco," "snus," and "Skoal." After eliminating videos that were not about ST (n = 26), non-English (n = 14), or duplicate (n = 42), a final sample of 78 unique videos was coded for overall portrayal, genre, and various content measures. RESULTS: Among the 78 unique videos, 15.4% were anti-ST, while 74.4% were pro-ST. Researchers were unable to determine the portrayal of ST in the remaining 10.3% of videos because they involved excessive or "sensationalized" use of the ST, which could be interpreted either positively or negatively, depending on the viewer. The most common ST genre was positive video diaries (or "vlogs"), which made up almost one third of the videos (29.5%), followed by promotional advertisements (20.5%) and anti-ST public service announcements (12.8%). While YouTube is intended for user-generated content, 23.1% of the videos were created by professional organizations. CONCLUSIONS: These results demonstrate that ST videos on YouTube are overwhelmingly pro-ST. More research is needed to determine who is viewing these ST YouTube videos and how they may affect people's knowledge, attitudes, and behaviors regarding ST use. PMID- 22080586 TI - Smokeless tobacco advertising at the point of sale: prevalence, placement, and demographic correlates. AB - INTRODUCTION: We aimed to describe the prevalence, in-store location, and neighborhood predictors of point-of-sale smokeless tobacco advertising. METHODS: In 2007, we conducted assessments of smokeless tobacco advertising at the point of sale in 484 establishments, which held tobacco licenses and sold tobacco products in a Midwest metropolitan area. Associations between store characteristics, neighborhood characteristics (based on U.S. 2000 census block groups), and smokeless tobacco advertising were calculated. RESULTS: Advertisements for smokeless tobacco were found in 21% (n = 103) of stores. Approximately, 12% (n = 58) of stores had ads within 6 feet of the counter, 3% (n = 14) had ads less than 3 feet from the ground, and 2% (n = 9) had advertisement less than 1 foot from candy or snacks. The racial/ethnic composition and number of households on public assistance within the block group in which a store was situated were related to the amount of smokeless advertising in stores. For instance, having a higher proportion of the population identifying as White was associated with more advertising. Gas stations/convenience stores had more advertising than any other store types. Chain stores had double the amount of advertising as independent stores (p < .05) even after adjustment for other factors. CONCLUSIONS: Smokeless tobacco advertising is not uncommon even in an urban metropolitan community. These products are being advertised in a way that youth, especially those living in neighborhoods with certain demographic characteristics, can encounter. With Food and Drug Administration regulation, there are new opportunities to regulate advertising at the point of sale. PMID- 22080587 TI - Suicidal behavior, smoking, and familial vulnerability. AB - INTRODUCTION: Smoking is a well-established correlate of suicidal behavior. It is not known if familial risk factors contribute to this association. METHODS: Data were obtained via semistructured interviews with 1,107 twin fathers, 1,919 offspring between ages 12-32 years, and 1,023 mothers. Familial vulnerability to nicotine dependence and suicidal behavior was modeled via father and maternal self-report of these behaviors. Multinomial logistic regression models were computed with and without familial risk factors to estimate the association between offspring ever smoking, regular smoking, nicotine dependence, and a 4 level offspring suicide variable: (a) none, (b) ideation, (c) ideation + plan, and (d) ideation + plan + attempt or ideation + attempt. All models were stratified by gender and adjusted for sociodemographics, familial risk factors including parental suicidal behavior, nicotine dependence, and conduct disorder, and offspring conduct disorder, depression, alcohol abuse/dependence, and illicit drug abuse/dependence. RESULTS: After adjusting for covariates and familial risk factors, ever smoking was not significantly associated with suicidal behavior in males and females. In males, regular smoking was associated with ideation + plan (odds ratio [OR] = 5.47; 95% CI: 1.05-28.60), and in females, regular smoking was associated with ideation + plan + attempt or ideation + attempt. In both genders, nicotine-dependent smoking was associated with ideation + plan + attempt or ideation + attempt (males: OR = 6.59; 95% CI: 1.91-22.70, females: OR = 3.37; 95% CI: 1.25-9.04). Comparison of models with and without familial risk factors indicated that there is no mediation of smoking status and suicidal behavior by familial risk. CONCLUSIONS: Smoking and nicotine dependence are correlated with suicidal behaviour. Contributions from familial risk factors did not significantly alter this association. PMID- 22080588 TI - A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates. AB - INTRODUCTION: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication. METHODS: In this double blind, randomized, placebo-controlled international study, smokers of >=10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24. RESULTS: Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively). CONCLUSIONS: Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies. PMID- 22080589 TI - Pulmonary oxidative stress is induced by maximal exercise in young cigarette smokers. AB - INTRODUCTION: Oxidative stress is induced by both cigarette smoking and acute exercise. It has also been reported that exercise can induce plasma oxidative stress in young cigarette smokers. However, no previous report has demonstrated that exercise induces pulmonary oxidative stress in cigarette smokers. The aim of this study was to determine whether pulmonary oxidative stress is induced by maximal exercise in cigarette smokers as measured by reactive oxygen species generation and total antioxidant content. METHODS: Fifteen male smokers (mean age: 25.9 +/- 2.9 years) and 18 male nonsmokers (mean age: 24.2 +/- 4.3 years) participated in this study. Hydrogen peroxide (H(2)O(2)) concentration and biological antioxidant potential (BAP) in exhaled breath condensate (EBC) were measured at baseline and after maximal exercise in the Wingate anaerobic test. RESULTS: A significant interaction of group by time was observed for EBC H2O2 concentration (p = .015). After exercise, EBC H(2)O(2) concentrations were significantly increased in the smoking group (p = .030) but not in the nonsmoking group. There were no significant changes in EBC BAP in either group. CONCLUSIONS: These findings indicate that in cigarette smokers, maximal exercise induces pulmonary oxidative stress, which may lead to oxidative damage in the lungs. PMID- 22080590 TI - Emergency management of chemical weapons injuries. AB - The potential for chemical weapons to be used in terrorism is a real possibility. Classes of chemical weapons include nerve agents, vesicants (blister agents), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. The nerve agents work by blocking the actions of acetylcholinesterase leading to a cholinergic syndrome. Nerve agents include sarin, tabun, VX, cyclosarin, and soman. The vesicants include sulfur mustard and lewisite. The vesicants produce blisters and also damage the upper airways. Choking agents include phosgene and chlorine gas. Choking agents cause pulmonary edema. Incapacitating agents include fentanyl and its derivatives and adamsite. Riot control agents include Mace and pepper spray. Blood agents include cyanide. The mechanism of toxicity for cyanide is blocking oxidative phosphorylation. Toxic industrial chemicals include agents such as formaldehyde, hydrofluoric acid, and ammonia. PMID- 22080591 TI - Arabidopsis family GT43 members are xylan xylosyltransferases required for the elongation of the xylan backbone. AB - Xylan is the second most abundant polysaccharide in plant biomass targeted for biofuel production. Therefore, it is imperative to understand the biochemical mechanism underlying xylan biosynthesis. Although previous genetic studies have identified several genes implicated in xylan biosynthesis, biochemical proof of any of their encoded proteins as a xylan xylosyltransferase (XylT) responsible for xylan backbone biosynthesis is still lacking. In this study, we investigated the enzymatic activities of two Arabidopsis thaliana GT43 members, IRX9 (Irregular Xylem9) and IRX14, which have been genetically shown to be non redundantly involved in the elongation of the xylan backbone. IRX9 and IRX14, alone or simultaneously, were heterologously expressed in tobacco BY2 cells, and microsomes isolated from the transgenic BY2 cells were tested for XylT activity using xylotetraose (Xyl(4)) as an acceptor and UDP-[(14)C]xylose as a donor. It was found that although microsomes with expression of IRX9 or IRX14 alone exhibited little incorporation of radiolabeled xylose, a high level of incorporation of radiolabeled xylose onto Xyl(4) was conferred by microsomes with co-expression of IRX9 and IRX14. Further analysis using fluorescent anthranilic acid-labeled xylotetraose (Xyl(4)-AA) as an acceptor revealed that up to five beta-(1,4)-linked xylosyl residues were able to be transferred onto Xyl(4)-AA by microsomes with co-expression of IRX9 and IRX14. Furthermore, it was shown that xylooligomers ranging from Xyl(3)-AA to Xyl(6)-AA could all be used as acceptors for the xylosyl transfer by microsomes with co-expression of IRX9 and IRX14. Together, these findings provide the first biochemical evidence that IRX9 and IRX14 are xylosyltransferases that operate cooperatively in the elongation of the xylan backbone. PMID- 22080592 TI - Acute pain associated with oxaliplatin infusion: case report and literature review. AB - Both acute and chronic neurotoxicities are well-described with the use of oxaliplatin. We describe the case of a 50-year-old man with Dukes C colon carcinoma being treated with an adjuvant FOLFOX4 (5-fluorouracil, leucovorin and oxaliplatin (85 mg/m(2) per cycle)) who developed a widespread acute pain 5 min after commencing his twelfth cycle of chemotherapy. The pain was disabling and distressing, and remained for 16 h despite multimodality analgesia. The patient was not rechallenged with oxaliplatin. We believe this presentation represents an acute neurological phenomenon relating to oxaliplatin. Of note, this acute reaction occurred after 11 cycles of treatment, significantly later in the treatment course than other reports of atypical acute reactions. PMID- 22080593 TI - Simulation of unilateral equinus using an adjustable orthosis in children: design, feasibility and biomechanical effects. AB - BACKGROUND AND AIM: In order to increase understanding of the biomechanical consequences of equinus foot on gait, we developed an orthosis to induce an adjustable degree of unilateral equinus. The aim of this study was to evaluate its feasibility and consequences on 3D ankle kinematics and kinetics. TECHNIQUE: 3D gait analysis was carried out in 10 healthy children without the orthosis, with the non-adjusted orthosis and with the orthosis adjusted to +10 degrees , 0 degrees , -10 degrees , -20 degrees of ankle dorsiflexion and maximum plantarflexion (MP). The amount of dorsiflexion at initial contact was close to the goniometric measurement. Significant kinematic and kinetic changes occurred at -10 degrees , -20 degrees and MP. The mean maximum equinus at initial contact -21.65 degrees +/- 4.17 and during stance -11.61 degrees +/- 4.82 were larger than those obtained with previous described devices. DISCUSSION: Our device was easy-to-use and induced an adjustable, well tolerated equinus. It provides a new way to simulate equinus and its biomechanical consequences on gait. PMID- 22080594 TI - The cardioprotective effects of parathyroid hormone are independent of endogenous granulocyte-colony stimulating factor release. AB - AIMS: Parathyroid hormone (PTH) administration after myocardial infarction (MI) is known to attenuate ischaemic cardiomyopathy. This effect mainly resulted from an increase in mobilization and homing of CD34+/CD45+ cells into the ischaemic myocardium. PTH-related stem cell mobilization was shown to be related to endogenous granulocyte-colony stimulating factor (G-CSF) release. The aim of our study is to determine the role of G-CSF on the cardioprotective effects of PTH. METHODS AND RESULTS: G-CSF +/+ (C57BL/6) and G-CSF -/- mice were treated with PTH for 6 days after inducing a MI. The myocardial homing factor stromal cell-derived factor-1 (SDF-1) was analysed on day 2 with enzyme-linked immunosorbent assay. Stem cell populations in peripheral blood and hearts were examined by FACS on days 6 and 2, respectively. Cardiac function and immunohistochemistry were investigated on day 6 and day 30. PTH treatment resulted in a significant increase in CD45+/CD34+ cells in peripheral blood in G-CSF +/+ but not in G-CSF /- mice. However, a significant increase in SDF-1 and enhanced migration of CD45+/CD34+ cells into the ischaemic myocardium was revealed after PTH administration in both G-CSF +/+ and G-CSF -/- mice. Enhanced stem cell homing was associated with improved cardiac function and post-MI survival after PTH treatment. Furthermore, infarct size, wall thickness, and neovascularization showed a significant improvement in both groups 30 days after MI. CONCLUSION: The cardioprotective effects of PTH were shown to be independent of endogenous G-CSF release and therefore from stem cell mobilization. This puts more emphasis on the role of stem cell homing into ischaemic myocardium. PMID- 22080595 TI - Bayesian inference for an illness-death model for stroke with cognition as a latent time-dependent risk factor. AB - Longitudinal data can be used to estimate the transition intensities between healthy and unhealthy states prior to death. An illness-death model for history of stroke is presented, where time-dependent transition intensities are regressed on a latent variable representing cognitive function. The change of this function over time is described by a linear growth model with random effects. Occasion specific cognitive function is measured by an item response model for longitudinal scores on the Mini-Mental State Examination, a questionnaire used to screen for cognitive impairment. The illness-death model will be used to identify and to explore the relationship between occasion-specific cognitive function and stroke. Combining a multi-state model with the latent growth model defines a joint model which extends current statistical inference regarding disease progression and cognitive function. Markov chain Monte Carlo methods are used for Bayesian inference. Data stem from the Medical Research Council Cognitive Function and Ageing Study in the UK (1991-2005). PMID- 22080596 TI - Regulation of compound leaf development in Medicago truncatula by fused compound leaf1, a class M KNOX gene. AB - Medicago truncatula is a legume species belonging to the inverted repeat lacking clade (IRLC) with trifoliolate compound leaves. However, the regulatory mechanisms underlying development of trifoliolate leaves in legumes remain largely unknown. Here, we report isolation and characterization of fused compound leaf1 (fcl1) mutants of M. truncatula. Phenotypic analysis suggests that FCL1 plays a positive role in boundary separation and proximal-distal axis development of compound leaves. Map-based cloning indicates that FCL1 encodes a class M KNOX protein that harbors the MEINOX domain but lacks the homeodomain. Yeast two hybrid assays show that FCL1 interacts with a subset of Arabidopsis thaliana BEL1 like proteins with slightly different substrate specificities from the Arabidopsis homolog KNATM-B. Double mutant analyses with M. truncatula single leaflet1 (sgl1) and palmate-like pentafoliata1 (palm1) leaf mutants show that fcl1 is epistatic to palm1 and sgl1 is epistatic to fcl1 in terms of leaf complexity and that SGL1 and FCL1 act additively and are required for petiole development. Previous studies have shown that the canonical KNOX proteins are not involved in compound leaf development in IRLC legumes. The identification of FCL1 supports the role of a truncated KNOX protein in compound leaf development in M. truncatula. PMID- 22080598 TI - Transcriptional regulation of Arabidopsis LEAFY COTYLEDON2 involves RLE, a cis element that regulates trimethylation of histone H3 at lysine-27. AB - LEAFY COTYLEDON2 (LEC2) is a master regulator of seed development in Arabidopsis thaliana. In vegetative organs, LEC2 expression is negatively regulated by Polycomb Repressive Complex2 (PRC2) that catalyzes histone H3 Lys 27 trimethylation (H3K27me3) and plays a crucial role in developmental phase transitions. To characterize the cis-regulatory elements involved in the transcriptional regulation of LEC2, molecular dissections and functional analyses of the promoter region were performed in vitro, both in yeast and in planta. Two cis-activating elements and a cis-repressing element (RLE) that is required for H3K27me3 marking were characterized. Remarkably, insertion of the RLE cis-element into pF3H, an unrelated promoter, is sufficient for repressing its transcriptional activity in different tissues. Besides improving our understanding of LEC2 regulation, this study provides important new insights into the mechanisms underlying H3K27me3 deposition and PRC2 recruitment at a specific locus in plants. PMID- 22080597 TI - Euchromatic subdomains in rice centromeres are associated with genes and transcription. AB - The presence of the centromere-specific histone H3 variant, CENH3, defines centromeric (CEN) chromatin, but poorly understood epigenetic mechanisms determine its establishment and maintenance. CEN chromatin is embedded within pericentromeric heterochromatin in most higher eukaryotes, but, interestingly, it can show euchromatic characteristics; for example, the euchromatic histone modification mark dimethylated H3 Lys 4 (H3K4me2) is uniquely associated with animal centromeres. To examine the histone marks and chromatin properties of plant centromeres, we developed a genomic tiling array for four fully sequenced rice (Oryza sativa) centromeres and used chromatin immunoprecipitation-chip to study the patterns of four euchromatic histone modification marks: H3K4me2, trimethylated H3 Lys 4, trimethylated H3 Lys 36, and acetylated H3 Lys 4, 9. The vast majority of the four histone marks were associated with genes located in the H3 subdomains within the centromere cores. We demonstrate that H3K4me2 is not a ubiquitous component of rice CEN chromatin, and the euchromatic characteristics of rice CEN chromatin are hallmarks of the transcribed sequences embedded in the centromeric H3 subdomains. We propose that the transcribed sequences located in rice centromeres may provide a barrier preventing loading of CENH3 into the H3 subdomains. The separation of CENH3 and H3 subdomains in the centromere core may be favorable for the formation of three-dimensional centromere structure and for rice centromere function. PMID- 22080599 TI - The Arabidopsis glucosyltransferase UGT76B1 conjugates isoleucic acid and modulates plant defense and senescence. AB - Plants coordinate and tightly regulate pathogen defense by the mostly antagonistic salicylate (SA)- and jasmonate (JA)-mediated signaling pathways. Here, we show that the previously uncharacterized glucosyltransferase UGT76B1 is a novel player in this SA-JA signaling crosstalk. UGT76B1 was selected as the top stress-induced isoform among all 122 members of the Arabidopsis thaliana UGT family. Loss of UGT76B1 function leads to enhanced resistance to the biotrophic pathogen Pseudomonas syringae and accelerated senescence but increased susceptibility toward necrotrophic Alternaria brassicicola. This is accompanied by constitutively elevated SA levels and SA-related marker gene expression, whereas JA-dependent markers are repressed. Conversely, UGT76B1 overexpression has the opposite effect. Thus, UGT76B1 attenuates SA-dependent plant defense in the absence of infection, promotes the JA response, and delays senescence. The ugt76b1 phenotypes were SA dependent, whereas UGT76B1 overexpression indicated that this gene possibly also has a direct effect on the JA pathway. Nontargeted metabolomic analysis of UGT76B1 knockout and overexpression lines using ultra high-resolution mass spectrometry and activity assays with the recombinant enzyme led to the ab initio identification of isoleucic acid (2-hydroxy-3-methyl pentanoic acid) as a substrate of UGT76B1. Exogenously applied isoleucic acid increased resistance against P. syringae infection. These findings indicate a novel link between amino acid-related molecules and plant defense that is mediated by small-molecule glucosylation. PMID- 22080600 TI - AXY8 encodes an alpha-fucosidase, underscoring the importance of apoplastic metabolism on the fine structure of Arabidopsis cell wall polysaccharides. AB - An Arabidopsis thaliana mutant with an altered structure of its hemicellulose xyloglucan (XyG; axy-8) identified by a forward genetic screen facilitating oligosaccharide mass profiling was characterized. axy8 exhibits increased XyG fucosylation and the occurrence of XyG fragments not present in the wild-type plant. AXY8 was identified to encode an alpha-fucosidase acting on XyG that was previously designated FUC95A. Green fluorescent protein fusion localization studies and analysis of nascent XyG in microsomal preparations demonstrated that this glycosylhydrolase acts mainly on XyG in the apoplast. Detailed structural analysis of XyG in axy8 gave unique insights into the role of the fucosidase in XyG metabolism in vivo. The genetic evidence indicates that the activity of glycosylhydrolases in the apoplast plays a major role in generating the heterogeneity of XyG side chains in the wall. Furthermore, without the dominant apoplastic glycosylhydrolases, the XyG structure in the wall is mainly composed of XXXG and XXFG subunits. PMID- 22080601 TI - Overlapping photoprotective function of vitamin E and carotenoids in Chlamydomonas. AB - Tocopherols (vitamin E) and carotenoids are the two most abundant groups of lipid soluble antioxidants in the chloroplast. Carotenoids are well known for their roles in protecting against photooxidative stress, whereas the photoprotective functions of tocopherols have only recently been examined experimentally. In addition, little is known about the functional overlap of carotenoids and tocopherols in vivo. To investigate this possible overlap, Chlamydomonas reinhardtii strains were engineered to overproduce tocopherols by chloroplast transformation with non-codon-optimized and codon-optimized versions of the homogentisate phytyltransferase vitamin E2 (VTE2) from Synechocystis and by nuclear transformation with VTE2 from C. reinhardtii, which resulted in 1.6-fold, 5-fold to 10-fold, and more than 10-fold increases in total tocopherol content, respectively. To test if tocopherol overproduction can compensate for carotenoid deficiency in terms of antioxidant function, the nuclear VTE2 gene from C. reinhardtii was overexpressed in the npq1 lor1 double mutant, which lacks zeaxanthin and lutein. Following transfer to high light, the npq1 lor1 strains that overaccumulated tocopherols showed increased resistance for up to 2 d and higher efficiency of photosystem II, and they were also much more resistant to other oxidative stresses. These results suggest an overlapping functions of tocopherols and carotenoids in protection against photooxidative stress. PMID- 22080602 TI - Repression of sucrose/ultraviolet B light-induced flavonoid accumulation in microbe-associated molecular pattern-triggered immunity in Arabidopsis. AB - Recognition of microbe-associated molecular patterns (MAMPs) leads to the generation of MAMP-triggered immunity (MTI), which restricts the invasion and propagation of potentially infectious microbes. It has been described that the perception of different bacterial and fungal MAMPs causes the repression of flavonoid induction upon light stress or sucrose application. However, the functional significance of this MTI-associated signaling output remains unknown. In Arabidopsis (Arabidopsis thaliana), FLAGELLIN-SENSING2 (FLS2) and EF-TU RECEPTOR act as the pattern recognition receptors for the bacterial MAMP epitopes flg22 (of flagellin) and elf18 (of elongation factor [EF]-Tu), respectively. Here, we reveal that reactive oxygen species spiking and callose deposition are dispensable for the repression of flavonoid accumulation by both pattern recognition receptors. Importantly, FLS2-triggered activation of PATHOGENESIS RELATED (PR) genes and bacterial basal defenses are enhanced in transparent testa4 plants that are devoid of flavonoids, providing evidence for a functional contribution of flavonoid repression to MTI. Moreover, we identify nine small molecules, of which eight are structurally unrelated, that derepress flavonoid accumulation in the presence of flg22. These compounds allowed us to dissect the FLS2 pathway. Remarkably, one of the identified compounds uncouples flavonoid repression and PR gene activation from the activation of reactive oxygen species, mitogen-activated protein kinases, and callose deposition, corroborating a close link between the former two outputs. Together, our data imply a model in which MAMP-induced repression of flavonoid accumulation serves a role in removing the inherent inhibitory action of flavonoids on an MTI signaling branch. PMID- 22080604 TI - Arginine residues at internal positions in a protein are always charged. AB - Many functionally essential ionizable groups are buried in the hydrophobic interior of proteins. A systematic study of Lys, Asp, and Glu residues at 25 internal positions in staphylococcal nuclease showed that their pK(a) values can be highly anomalous, some shifted by as many as 5.7 pH units relative to normal pK(a) values in water. Here we show that, in contrast, Arg residues at the same internal positions exhibit no detectable shifts in pK(a); they are all charged at pH <= 10. Twenty-three of these 25 variants with Arg are folded at both pH 7 and 10. The mean decrease in thermodynamic stability from substitution with Arg was 6.2 kcal/mol at this pH, comparable to that for substitution with Lys, Asp, or Glu at pH 7. The physical basis behind the remarkable ability of Arg residues to remain protonated in environments otherwise incompatible with charges is suggested by crystal structures of three variants showing how the guanidinium moiety of the Arg side chain is effectively neutralized through multiple hydrogen bonds to protein polar atoms and to site-bound water molecules. The length of the Arg side chain, and slight deformations of the protein, facilitate placement of the guanidinium moieties near polar groups or bulk water. This unique capacity of Arg side chains to retain their charge in dehydrated environments likely contributes toward the important functional roles of internal Arg residues in situations where a charge is needed in the interior of a protein, in a lipid bilayer, or in similarly hydrophobic environments. PMID- 22080603 TI - Potato snakin-1 gene silencing affects cell division, primary metabolism, and cell wall composition. AB - Snakin-1 (SN1) is an antimicrobial cysteine-rich peptide isolated from potato (Solanum tuberosum) that was classified as a member of the Snakin/Gibberellic Acid Stimulated in Arabidopsis protein family. In this work, a transgenic approach was used to study the role of SN1 in planta. Even when overexpressing SN1, potato lines did not show remarkable morphological differences from the wild type; SN1 silencing resulted in reduced height, which was accompanied by an overall reduction in leaf size and severe alterations of leaf shape. Analysis of the adaxial epidermis of mature leaves revealed that silenced lines had 70% to 90% increases in mean cell size with respect to wild-type leaves. Consequently, the number of epidermal cells was significantly reduced in these lines. Confocal microscopy analysis after agroinfiltration of Nicotiana benthamiana leaves showed that SN1-green fluorescent protein fusion protein was localized in plasma membrane, and bimolecular fluorescence complementation assays revealed that SN1 self-interacted in vivo. We further focused our study on leaf metabolism by applying a combination of gas chromatography coupled to mass spectrometry, Fourier transform infrared spectroscopy, and spectrophotometric techniques. These targeted analyses allowed a detailed examination of the changes occurring in 46 intermediate compounds from primary metabolic pathways and in seven cell wall constituents. We demonstrated that SN1 silencing affects cell division, leaf primary metabolism, and cell wall composition in potato plants, suggesting that SN1 has additional roles in growth and development beyond its previously assigned role in plant defense. PMID- 22080605 TI - beta-catenin/TCF4 complex induces the epithelial-to-mesenchymal transition (EMT) activator ZEB1 to regulate tumor invasiveness. AB - In most carcinomas, invasion of malignant cells into surrounding tissues involves their molecular reprogramming as part of an epithelial-to-mesenchymal transition (EMT). Mutation of the APC gene in most colorectal carcinomas (CRCs) contributes to the nuclear translocation of the oncoprotein beta-catenin that upon binding to T-cell and lymphoid enhancer (TCF-LEF) factors triggers an EMT and a proinvasive gene expression profile. A key inducer of EMT is the ZEB1 transcription factor whose expression promotes tumorigenesis and metastasis in carcinomas. As inhibitor of the epithelial phenotype, ZEB1 is never present in the epithelium of normal colon or the tumor center of CRCs where beta-catenin remains membranous. We show here that ZEB1 is expressed by epithelial cells in intestinal tumors from human patients (familial adenomatous polyposis) and mouse models (APC(Min/+)) with germline mutations of APC that result in nuclear accumulation of beta catenin. However, ZEB1 is not expressed in the epithelium of hereditary forms of CRCs that carry wild-type APC and where beta-catenin is excluded from the nucleus (Lynch syndrome). We found that beta-catenin/TCF4 binds directly to the ZEB1 promoter and activates its transcription. Knockdown of beta-catenin and TCF4 in APC-mutated CRC cells inhibited endogenous ZEB1, whereas forced translocation of beta-catenin to the nucleus in APC-wild-type CRC cells induced de novo expression of ZEB1. Upregulation of MT1-MMP and LAMC2 by beta-catenin/TCF4 has been linked to invasiveness in CRCs, and we show here that both proteins are activated by ZEB1 coexpressing with it in primary colorectal tumors with mutated APC. These results set ZEB1 as an effector of beta-catenin/TCF4 signaling in EMT and tumor progression. PMID- 22080606 TI - Excited states of ribosome translocation revealed through integrative molecular modeling. AB - The dynamic nature of biomolecules leads to significant challenges when characterizing the structural properties associated with function. While X-ray crystallography and imaging techniques (such as cryo-electron microscopy) can reveal the structural details of stable molecular complexes, strategies must be developed to characterize configurations that exhibit only marginal stability (such as intermediates) or configurations that do not correspond to minima on the energy landscape (such as transition-state ensembles). Here, we present a methodology (MDfit) that utilizes molecular dynamics simulations to generate configurations of excited states that are consistent with available biophysical and biochemical measurements. To demonstrate the approach, we present a sequence of configurations that are suggested to be associated with transfer RNA (tRNA) movement through the ribosome (translocation). The models were constructed by combining information from X-ray crystallography, cryo-electron microscopy, and biochemical data. These models provide a structural framework for translocation that may be further investigated experimentally and theoretically to determine the precise energetic character of each configuration and the transition dynamics between them. PMID- 22080608 TI - A triplet spike-timing-dependent plasticity model generalizes the Bienenstock Cooper-Munro rule to higher-order spatiotemporal correlations. AB - Synaptic strength depresses for low and potentiates for high activation of the postsynaptic neuron. This feature is a key property of the Bienenstock-Cooper Munro (BCM) synaptic learning rule, which has been shown to maximize the selectivity of the postsynaptic neuron, and thereby offers a possible explanation for experience-dependent cortical plasticity such as orientation selectivity. However, the BCM framework is rate-based and a significant amount of recent work has shown that synaptic plasticity also depends on the precise timing of presynaptic and postsynaptic spikes. Here we consider a triplet model of spike timing-dependent plasticity (STDP) that depends on the interactions of three precisely timed spikes. Triplet STDP has been shown to describe plasticity experiments that the classical STDP rule, based on pairs of spikes, has failed to capture. In the case of rate-based patterns, we show a tight correspondence between the triplet STDP rule and the BCM rule. We analytically demonstrate the selectivity property of the triplet STDP rule for orthogonal inputs and perform numerical simulations for nonorthogonal inputs. Moreover, in contrast to BCM, we show that triplet STDP can also induce selectivity for input patterns consisting of higher-order spatiotemporal correlations, which exist in natural stimuli and have been measured in the brain. We show that this sensitivity to higher-order correlations can be used to develop direction and speed selectivity. PMID- 22080607 TI - Dendritic SNAREs add a new twist to the old neuron theory. AB - Dendritic exocytosis underpins a broad range of integrative and homeostatic synaptic functions. Emerging data highlight the essential role of SNAREs in trafficking and fusion of secretory organelles with release of peptides and neurotransmitters from dendrites. This Perspective analyzes recent evidence inferring axo-dendritic polarization of vesicular release machinery and pinpoints progress made with existing challenges in this rapidly progressing field of dendritic research. Interpreting the relation of new molecular data to physiological results on secretion from dendrites would greatly advance our understanding of this facet of neuronal mechanisms. PMID- 22080609 TI - Profile of Tak Wah Mak. PMID- 22080610 TI - Decrease in topoisomerase I is responsible for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation. AB - Somatic hypermutation (SHM) and class-switch recombination (CSR) of the Ig gene require both the transcription of the locus and the expression of activation induced cytidine deaminase (AID). During CSR, AID decreases the amount of topoisomerase I (Top1); this decrease alters the DNA structure and induces cleavage in the S region. Similarly, Top1 is involved in transcription-associated mutation at dinucleotide repeats in yeast and in triplet-repeat contraction in mammals. Here, we report that the AID-induced decrease in Top1 is critical for SHM. Top1 knockdown or haploinsufficiency enhanced SHM, whereas Top1 overexpression down-regulated it. A specific Top1 inhibitor, camptothecin, suppressed SHM, indicating that Top1's activity is required for DNA cleavage. Nonetheless, suppression of transcription abolished SHM, even in cells with Top1 knockdown, suggesting that transcription is critical. These results are consistent with a model proposed for CSR and triplet instability, in which transcription-induced non-B structure formation is enhanced by Top1 reduction and provides the target for irreversible cleavage by Top1. We speculate that the mechanism for transcription-coupled genome instability was adopted to generate immune diversity when AID evolved. PMID- 22080611 TI - Protein kinase Ypk1 phosphorylates regulatory proteins Orm1 and Orm2 to control sphingolipid homeostasis in Saccharomyces cerevisiae. AB - The Orm family proteins are conserved integral membrane proteins of the endoplasmic reticulum that are key homeostatic regulators of sphingolipid biosynthesis. Orm proteins bind to and inhibit serine:palmitoyl-coenzyme A transferase, the first enzyme in sphingolipid biosynthesis. In Saccharomyces cerevisiae, Orm1 and Orm2 are inactivated by phosphorylation in response to compromised sphingolipid synthesis (e.g., upon addition of inhibitor myriocin), thereby restoring sphingolipid production. We show here that protein kinase Ypk1, one of an essential pair of protein kinases, is responsible for this regulatory modification. Myriocin-induced hyperphosphorylation of Orm1 and Orm2 does not occur in ypk1 cells, and immunopurified Ypk1 phosphorylates Orm1 and Orm2 robustly in vitro exclusively on three residues that are known myriocin-induced sites. Furthermore, the temperature-sensitive growth of ypk1(ts) ypk2 cells is substantially ameliorated by deletion of ORM genes, confirming that a primary physiological role of Ypk1-mediated phosphorylation is to negatively regulate Orm function. Ypk1 immunoprecipitated from myriocin-treated cells displays a higher specific activity for Orm phosphorylation than Ypk1 from untreated cells. To identify the mechanism underlying Ypk1 activation, we systematically tested several candidate factors and found that the target of rapamycin complex 2 (TORC2) kinase plays a key role. In agreement with prior evidence that a TORC2 dependent site in Ypk1(T662) is necessary for cells to exhibit a wild-type level of myriocin resistance, a Ypk1(T662A) mutant displays only weak Orm phosphorylation in vivo and only weak activation in vitro in response to sphingolipid depletion. Additionally, sphingolipid depletion increases phosphorylation of Ypk1 at T662. Thus, Ypk1 is both a sensor and effector of sphingolipid level, and reduction in sphingolipids stimulates Ypk1, at least in part, via TORC2-dependent phosphorylation. PMID- 22080613 TI - Density minimum in supercooled confined water. PMID- 22080614 TI - DEGAS: sharing and tracking target compound ideas with external collaborators. AB - To minimize the risk of failure in clinical trials, drug discovery teams must propose active and selective clinical candidates with good physicochemical properties. An additional challenge is that today drug discovery is often conducted by teams at different geographical locations. To improve the collaborative decision making on which compounds to synthesize, we have implemented DEGAS, an application which enables scientists from Genentech and from collaborating external partners to instantly access the same data. DEGAS was implemented to ensure that only the best target compounds are made and that they are made without duplicate effort. Physicochemical properties and DMPK model predictions are computed for each compound to allow the team to make informed decisions when prioritizing. The synthesis progress can be easily tracked. While developing DEGAS, ease of use was a particular goal in order to minimize the difficulty of training and supporting remote users. PMID- 22080612 TI - beta2-Adrenoceptor agonist-induced RGS2 expression is a genomic mechanism of bronchoprotection that is enhanced by glucocorticoids. AB - In asthma and chronic obstructive pulmonary disease, activation of G(q)-protein coupled receptors causes bronchoconstriction. In each case, the management of moderate-to-severe disease uses inhaled corticosteroid (glucocorticoid)/long acting beta(2)-adrenoceptor agonist (LABA) combination therapies, which are more efficacious than either monotherapy alone. In primary human airway smooth muscle cells, glucocorticoid/LABA combinations synergistically induce the expression of regulator of G-protein signaling 2 (RGS2), a GTPase-activating protein that attenuates G(q) signaling. Functionally, RGS2 reduced intracellular free calcium flux elicited by histamine, methacholine, leukotrienes, and other spasmogens. Furthermore, protection against spasmogen-increased intracellular free calcium, following treatment for 6 h with LABA plus corticosteroid, was dependent on RGS2. Finally, Rgs2-deficient mice revealed enhanced bronchoconstriction to spasmogens and an absence of LABA-induced bronchoprotection. These data identify RGS2 gene expression as a genomic mechanism of bronchoprotection that is induced by glucocorticoids plus LABAs in human airway smooth muscle and provide a rational explanation for the clinical efficacy of inhaled corticosteroid (glucocorticoid)/LABA combinations in obstructive airways diseases. PMID- 22080615 TI - Milk from cows of different beta-casein genotypes as a source of beta-casomorphin 7. AB - The aim of this study was to quantify beta-casomorphin-7 in raw, hydrolyzed and processed milk in different stages of the cow lactation. The obtained results lead to the following conclusion: the highest amount of beta-casomorphin-7 released from the hydrolyzed and processed milk is related to the beta-casein A1 allele, irrespective of a lactation period. Some traces of beta-casomorphin-7 in milk from cows with the beta-casein A2 variant are probably a result of the acid hydrolysis of beta-casein during its digestion with pepsin. It has been shown that processing of raw milk at high temperatures affects, in a slight degree, the differences between beta-casomorphins-7 originating from different beta-casein genotypes. The obtained results suggest a possibility to provide a new nutritional factor for milk quality based on the content of beta-casomorphin-7 liberated in vivo from milk digested by a mixture of the gastrointestinal enzymes. PMID- 22080616 TI - Association of chemerin levels in synovial fluid with the severity of knee osteoarthritis. AB - CONTEXT: Chemerin has been implicated to be correlated with inflammation. OBJECTIVE: This study aims to determine the association of chemerin levels in serum and synovial fluid (SF) with the disease severity of patients with knee Osteoarthritis (OA). METHODS: 124 patients with knee OA and 76 healthy controls were enrolled in this study. RESULTS: Chemerin levels in serum were significant higher with regard to paired SF. Chemerin levles in SF of knee OA patients were correlated with disease severity evaluated by KL grading criteria. CONCLUSION: Chemerin levels may be involved in the pathophysiology of the development and progression of OA. PMID- 22080617 TI - Ages and Stages Questionnaire as a screening tool for developmental delay in Indian children. AB - OBJECTIVE: To evaluate the ability of Ages and Stages Questionnaire, a parent completed developmental screening questionnaire to detect developmental delay in Indian children. DESIGN: Cross-sectional study. SETTING: Child Development Clinic of a tertiary care center located in Northern India. PARTICIPANTS AND METHODS: 200 children, 50 each in the age groups of 4+/-1, 10+/-1, 18+/-1 and 24+/-1 months were recruited (20 high risks and 30 low risks in each age group). The Ages and Stages Questionnaire (ASQ) was translated into Hindi and administered to the parents, followed by standardized development assessment using Developmental Assessment Scale for Indian Infants (DASII). RESULTS: 102 (51%) children failed on ASQ and 90 (45%) children failed on DASII. The overall sensitivity of ASQ for detecting developmental delay was 83.3% and specificity was 75.4%. The sensitivity was best for the 24-months questionnaire (94.7%) and specificity was best for the 4-month questionnaire (86.4%). The sensitivity of ASQ was much higher in the high risk group (92.3%) as compared to the low risk group (60%). CONCLUSION: ASQ has strong test characteristics for detecting developmental delay in Indian children, especially in high risk cases. It may be easily converted into other Indian languages and used widely for developmental screening. PMID- 22080618 TI - Differences in evolution of children with non-severe acute lower respiratory tract infection with and without radiographically diagnosed pneumonia. AB - OBJECTIVE: To identify differences in the evolution of children with non-severe acute lower respiratory tract infection between those with and without radiographically diagnosed pneumonia. DESIGN: Prospective cohort study. SETTING: A public university pediatric hospital in Salvador, Northeast Brazil. PATIENTS: Children aged 2-59 months. METHODS: By active surveillance, the pneumonia cases were prospectively identified in a 2-year period. Each case was followed-up for changes in various clinical symptoms and signs. Demographic, clinical and radiographic data were recorded in standardized forms. Exclusion was due to antibiotic use in the previous 48 hours, signs of severe disease, refusal to give informed consent, underlying chronic illness, hospitalization in the previous 7 days or amoxicillin allergy. Chest X-ray (CXR) was later read by at least 2 independent pediatric radiologists. MAIN OUTCOME MEASURES: Radiographic diagnosed pneumonia based on agreed detection of pulmonary infiltrate or pleural effusion in 2 assessments. RESULTS: A total of 382 patients receiving amoxicillin were studied, of whom, 372 (97.4%) had concordant radiographic diagnosis which was pneumonia (52%), normal CXR (41%) and others (7%). By multivariate analysis, age (OR=1.03; 95% CI: 1.02-1.05), disease > 5 days (OR = 1.04; 95% CI: 1.001-1.08), reduced pulmonary expansion (OR = 3.3; 95% CI: 1.4-8.0), absence of wheezing (OR = 0.5; 95% CI: 0.3-0.9), crackles on admission (OR = 2.0; 95% CI: 1.2-3.5), inability to drink on day 1 (OR = 4.2; 95% CI: 1.05-17.3), consolidation percussion sign (OR = 7.0; 95% CI: 1.5-32.3), tachypnea (OR = 2.0; 95% CI: 1.09 3.6) and fever (OR = 3.6; 95% CI: 1.4-9.4) on day 2 were independently associated with pneumonia. The highest positive predictive value was at the 2nd day of evolution for tachypnea (71.0%) and fever (81.1%). CONCLUSION: Persistence of fever or tachypnea up to the second day of amoxicillin treatment is predictive of radiographically diagnosed pneumonia among children with non-severe lower respiratory tract diseases. PMID- 22080619 TI - Nebulized hypertonic-saline vs epinephrine for bronchiolitis; proof of concept study of cumulative sum (CUSUM) analysis. AB - OBJECTIVE: To apply cumulative sum (CUSUM) to monitor a drug trial of nebulized hypertonic-saline in bronchiolitis. To test if monitoring with CUSUM control lines is practical and useful as a prompt to stop the drug trial early, if the study drug performs significantly worse than the comparator drug. DESIGN: Prospective, open label, controlled trial using standard therapy (epinephrine) and study drug (hypertonic-saline) sequentially in two groups of patients. SETTING: Hospital offering tertiary-level pediatric care. PATIENTS: Children, 2 months to 2 years, with first episode of bronchiolitis, excluding those with cardiac disease, immunodeficiency and critical illness at presentation. INTERVENTIONS: Nebulized epinephrine in first half of the bronchiolitis season (n = 35) and hypertonic saline subsequently (n = 29). Continuous monitoring of response to hypertonic-saline using CUSUM control charts developed with epinephrine-response data. MAIN OUTCOME MEASURES: Clinical score, tachycardia and total duration of hospital stay. RESULTS: In the epinephrine group, the maximum CUSUM was +2.25 (SD 1.34) and minimum CUSUM was -2.26 (SD 1.34). CUSUM score with hypertonic saline group stayed above the zero line throughout the study. There was no statistical difference in the post-treatment clinical score at 24 hours between the treatment groups {Mean (SD) 3.516 (2.816): 3.552 (2.686); 95% CI: 1.416 to 1.356}, heart rate {Mean (SD) 136 (44): 137(12); 95% CI: -17.849 to 15.849) or duration of hospital stay (Mean (SD) 96.029 (111.41): 82.914 (65.940); 95% CI: -33.888 to 60.128}. CONCLUSIONS: The software we developed allows for drawing of control lines to monitor study drug performance. Hypertonic saline performed as well or better than nebulized epinephrine in bronchiolitis. PMID- 22080620 TI - Survival after immunosuppressive therapy in children with aplastic anemia. AB - OBJECTIVE: To determine the survival of children =18 y, treated with immunosuppressive therapy (IST) using equine antithymocyte globulin (e-ATG) and cyclosporine (CsA). DESIGN: Prospective data entry as per a specified format. SETTING: Tertiary care hospital. PATIENTS: From January 1998 to December 2009, 40 children were diagnosed with acquired aplastic anemia; 33 patients, who received IST, were analyzed. 31 children (94%) received one course of e-ATG and CsA. 2 patients (6%) received two courses of ATG. INTERVENTION: Immunosuppressive therapy using equine ATG and cyclosporine. MAIN OUTCOME MEASURES: Overall response and overall survival. RESULTS: The overall response (complete response + partial response) to IST at 6 months was 87.9%. 8 (24.2%) patients achieved CR, 21 (63.6%) patients had PR and 4 (12.1%) patients did not respond to IST. Median follow-up was 24 (6-102) months. Overall survival at 24 months was 90%, with an actual survival of 85.4% at 5 years. Seventeen patients (51.5%) received G-CSF for a median duration of 32 (23-64) days. The patients who received G-CSF had fewer infectious complications (P=0.002), but G-CSF administration did not influence survival/ outcome. No patient developed myelodysplastic syndrome or acute leukemia. CONCLUSIONS: The survival of patients who respond to IST is excellent. Also, G-CSF reduces the infectious complications without conferring any survival advantage. PMID- 22080621 TI - Outcomes of hepatoblastoma in the Indian context. AB - A comprehensive review and critical appraisal of published and grey literature was undertaken to identify current treatment practices and outcomes of children with hepatoblastoma in India. Eight single-centre studies with 157 patients (range five to 36 patients in each study) were included. Pre-operative chemotherapy (mainly cisplatin and doxorubicin) followed by surgical resection and additional chemotherapy was the usual practice. There was no stratification of treatment by risk group in any of the studies. The median event-free survival ranged from 33-100%. The two main reasons for treatment failure were treatment related mortality (0-50%) and progression of disease (0-30%). PMID- 22080622 TI - NPHS2 mutations in Indian children with sporadic early steroid resistant nephrotic syndrome. AB - We examined the frequency and spectrum of podocin NPHS2 mutations in Indian children with sporadic steroid resistant nephrotic syndrome (SRNS). Of 25 children screened, only one (4%) had a pathogenic mutation resulting in a stop codon. The allele and genotype frequencies of the four known single nucleotide polymorphisms detected in the cohort were similar to that of controls. This finding emphasizes the need to screen for mutations in other genes involved in the pathogenesis of SRNS. PMID- 22080623 TI - Renal scarring and osteopontin gene C/T polymorphism in children with primary vesicoureteral reflux. AB - We examined for osteopontin (OPN) gene C/T polymorphism in 78 patients (53 girls) with vesicoureteric reflux, with or without renal scarring. The T allele frequency was associated with a significantly increased risk (26.4 fold) of renal scarring. PMID- 22080624 TI - T cell immunoglobulin and mucin-domain containing molecule 1 in peripheral blood mononuclear cells in Henoch Schonlein purpura. AB - The T cell immunoglobulin- and mucin domain-containing molecules (Tim) have been implicated in the pathogenesis of immune diseases. In this study, we used quantitative real time reverse transcription polymerase chain reaction to examine the Tim 1 mRNA expression in peripheral blood mononuclear cells from Henoch Schonlein purpura patients. The results showed that Tim1 mRNA expression was significantly higher in patients, which was closely correlated with serum TNFa, IL4 levels, IgA1 levels. PMID- 22080625 TI - Profile of patients with Von Gierke disease from India. AB - Molecular diagnosis of Von Gierke disease is possible by mutation analysis of G6PC gene. GSD type 1a cases account for 20 % of glycogenoses in our center. We diagnosed ten unrelated patients with glycogen storage disease based on clinical, biochemical and histopathology investigations. Mutation analysis was done by sequencing the G6PC gene. Two unrelated patients were found to be homozygous for a novel mutation c.355 C >; G (p.H119D). They were born to non-consanguineous parents from Karnataka. This suggests founder effect. Mutation detection confirms the diagnosis and assists in counseling and prenatal diagnosis. PMID- 22080626 TI - A copper-methionine interaction controls the pH-dependent activation of peptidylglycine monooxygenase. AB - The pH dependence of native peptidylglycine monooxygenase (PHM) and its M314H variant has been studied in detail. For wild-type (WT) PHM, the intensity of the Cu-S interaction visible in the Cu(I) extended X-ray absorption fine structure (EXAFS) data is inversely proportional to catalytic activity over the pH range of 3-8. A previous model based on more limited data was interpreted in terms of two protein conformations involving an inactive Met-on form and an active flexible Met-off form [Bauman, A. T., et al. (2006) Biochemistry 45, 11140-11150] that derived its catalytic activity from the ability to couple into vibrational modes critical for proton tunneling. The new studies comparing the WT and M314H variant have led to the evolution of this model, in which the Met-on form has been found to be derived from coordination of an additional Met residue, rather than a more rigid conformer of M314 as previously proposed. The catalytic activity of the mutant decreased by 96% because of effects on both k(cat) and K(M), but it displayed the same activity-pH profile with a maximum around pH 6. At pH 8, the reduced Cu(I) form gave spectra that could be simulated by replacement of the Cu(M) Cu-S(Met) interaction with a Cu-N/O interaction, but the data did not unambiguously assign the ligand to the imidazole side chain of H314. At pH 3.5, the EXAFS still showed the presence of a strong Cu-S interaction, establishing that the Met-on form observed at low pH in WT cannot be due to a strengthening of the Cu(M)-methionine interaction but must arise from a different Cu-S interaction. Therefore, lowering the pH causes a conformational change at one of the Cu centers that brings a new S donor residue into a favorable orientation for coordination to copper and generates an inactive form. Cys coordination is unlikely because all Cys residues in PHM are engaged in disulfide cross-links. Sequence comparison with the PHM homologues tyramine beta-monooxygenase and dopamine beta-monooxygenase suggests that M109 (adjacent to H site ligands H107 and H108) is the most likely candidate. A model is presented in which H108 is protonated with a pK(a) of 4.6 to generate the inactive low-pH form with Cu(H) coordinated by M109, H107, and H172. PMID- 22080627 TI - Use of the International Classification of Functioning, Disability and Health (ICF) in social services for elderly in Sweden. AB - PURPOSE: To examine the content of health information in acts of social services of elderly people in relation to the International Classification of Functioning, Disability and Health (ICF) and to describe the health information in the different parts of the acts according to the ICF. METHOD: Health information of 25 acts from four municipalities was analysed and the concepts were linked to ICF codes, using the established coding rules. RESULTS: The health information consisted of 372 concepts, which were linked to 122 specific ICF codes. The concepts in the acts were mostly linked to the ICF component Activities and Participation, except for the current functioning concepts where the ICF component Body functions was the most frequent. The 3rd level was most frequent in Activities and Participation and in Environmental factors, and the 2nd level was most frequent in Body functions. CONCLUSIONS: The ICF covers the concepts and terms contained in the acts to a large extent. Furthermore, the results show that the ICF codes differ in the different parts of the acts. The ICF provides a coherent and structured documentation, which contributes to a legally secure assessment of assistance. The selection of ICF codes can be used in development of "code sets" for social services for elderly. PMID- 22080628 TI - Parametric modelling and segmentation of vertebral bodies in 3D CT and MR spine images. AB - Accurate and objective evaluation of vertebral deformations is of significant importance in clinical diagnostics and therapy of pathological conditions affecting the spine. Although modern clinical practice is focused on three dimensional (3D) computed tomography (CT) and magnetic resonance (MR) imaging techniques, the established methods for evaluation of vertebral deformations are limited to measuring deformations in two-dimensional (2D) x-ray images. In this paper, we propose a method for quantitative description of vertebral body deformations by efficient modelling and segmentation of vertebral bodies in 3D. The deformations are evaluated from the parameters of a 3D superquadric model, which is initialized as an elliptical cylinder and then gradually deformed by introducing transformations that yield a more detailed representation of the vertebral body shape. After modelling the vertebral body shape with 25 clinically meaningful parameters and the vertebral body pose with six rigid body parameters, the 3D model is aligned to the observed vertebral body in the 3D image. The performance of the method was evaluated on 75 vertebrae from CT and 75 vertebrae from T(2)-weighted MR spine images, extracted from the thoracolumbar part of normal and pathological spines. The results show that the proposed method can be used for 3D segmentation of vertebral bodies in CT and MR images, as the proposed 3D model is able to describe both normal and pathological vertebral body deformations. The method may therefore be used for initialization of whole vertebra segmentation or for quantitative measurement of vertebral body deformations. PMID- 22080629 TI - Continuous chest compression cardiopulmonary resuscitation training promotes rescuer self-confidence and increased secondary training: a hospital-based randomized controlled trial*. AB - OBJECTIVE: Recent work suggests that delivery of continuous chest compression cardiopulmonary resuscitation is an acceptable layperson resuscitation strategy, although little is known about layperson preferences for training in continuous chest compression cardiopulmonary resuscitation. We hypothesized that continuous chest compression cardiopulmonary resuscitation education would lead to greater trainee confidence and would encourage wider dissemination of cardiopulmonary resuscitation skills compared to standard cardiopulmonary resuscitation training (30 compressions: two breaths). DESIGN: Prospective, multicenter randomized study. SETTING: Three academic medical center inpatient wards. SUBJECTS: Adult family members or friends (>= 18 yrs old) of inpatients admitted with cardiac related diagnoses. INTERVENTIONS: In a multicenter randomized trial, family members of hospitalized patients were trained via the educational method of video self-instruction. Subjects were randomized to continuous chest compression cardiopulmonary resuscitation or standard cardiopulmonary resuscitation educational modes. MEASUREMENTS: Cardiopulmonary resuscitation performance data were collected using a cardiopulmonary resuscitation skill-reporting manikin. Trainee perspectives and secondary training rates were assessed through mixed qualitative and quantitative survey instruments. MAIN RESULTS: Chest compression performance was similar in both groups. The trainees in the continuous chest compression cardiopulmonary resuscitation group were significantly more likely to express a desire to share their training kit with others (152 of 207 [73%] vs. 133 of 199 [67%], p = .03). Subjects were contacted 1 month after initial enrollment to assess actual sharing, or "secondary training." Kits were shared with 2.0 +/- 3.4 additional family members in the continuous chest compression cardiopulmonary resuscitation group vs. 1.2 +/- 2.2 in the standard cardiopulmonary resuscitation group (p = .03). As a secondary result, trainees in the continuous chest compression cardiopulmonary resuscitation group were more likely to rate themselves "very comfortable" with the idea of using cardiopulmonary resuscitation skills in actual events than the standard cardiopulmonary resuscitation trainees (71 of 207 [34%] vs. 57 of 199 [28%], p = .08). CONCLUSIONS: Continuous chest compression cardiopulmonary resuscitation education resulted in a statistically significant increase in secondary training. This work suggests that implementation of video self-instruction training programs using continuous chest compression cardiopulmonary resuscitation may confer broader dissemination of life-saving skills and may promote rescuer comfort with newly acquired cardiopulmonary resuscitation knowledge. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01260441. PMID- 22080630 TI - Timing of neuroprognostication in postcardiac arrest therapeutic hypothermia*. AB - OBJECTIVE: Early assessment of neurologic recovery is often challenging in survivors of cardiac arrest. Further, little is known about when to assess neurologic status in comatose, postarrest patients receiving therapeutic hypothermia. We sought to evaluate timing of prognostication in cardiac arrest survivors who received therapeutic hypothermia. DESIGN: A retrospective chart review of consecutive postarrest patients receiving therapeutic hypothermia (protocol: 24-hr maintenance at target temperature followed by rewarming over 8 hrs). Data were abstracted from the medical chart, including documentation during the first 96 hrs post arrest of "poor" prognosis, diagnostic tests for neuroprognostication, consultations used for determination of prognosis, and outcome at discharge. SETTING: Two academic urban emergency departments. PATIENTS: A total of 55 consecutive patients who underwent therapeutic hypothermia were reviewed between September 2005 and April 2009. INTERVENTION: None. RESULTS: Of our cohort of comatose postarrest patients, 59% (29 of 49) were male, and the mean age was 56 +/- 16 yrs. Chart documentation of "poor" or "grave" prognosis occurred "early": during induction, maintenance of cooling, rewarming, or within 15 hrs after normothermia in 57% (28 of 49) of cases. Of patients with early documentation of poor prognosis, 25% (seven of 28) had care withdrawn within 72 hrs post arrest, and 21% (six of 28) survived to discharge with favorable neurologic recovery. In the first 96 hrs post arrest: 88% (43 of 49) of patients received a head computed tomography, 90% (44 of 49) received electroencephalography, 2% (one of 49) received somatosensory evoked potential testing, and 71% (35 of 49) received neurology consultation. CONCLUSIONS: Documentation of "poor prognosis" occurred during therapeutic hypothermia in more than half of patients in our cohort. Premature documentation of poor prognosis may contribute to early decisions to withdraw care. Future guidelines should address when to best prognosticate in postarrest patients receiving therapeutic hypothermia. PMID- 22080631 TI - Cognitive and physical rehabilitation of intensive care unit survivors: results of the RETURN randomized controlled pilot investigation. AB - BACKGROUND: Millions of patients who survive medical and surgical general intensive care unit care every year experience newly acquired long-term cognitive impairment and profound physical and functional disabilities. To overcome the current reality in which patients receive inadequate rehabilitation, we devised a multifaceted, in-home, telerehabilitation program implemented using social workers and psychology technicians with the goal of improving cognitive and functional outcomes. METHODS: This was a single-site, feasibility, pilot, randomized trial of 21 general medical/surgical intensive care unit survivors (8 controls and 13 intervention patients) with either cognitive or functional impairment at hospital discharge. After discharge, study controls received usual care (sporadic rehabilitation), whereas intervention patients received a combination of in-home cognitive, physical, and functional rehabilitation over a 3-month period via a social worker or master's level psychology technician utilizing telemedicine to allow specialized multidisciplinary treatment. Interventions over 12 wks included six in-person visits for cognitive rehabilitation and six televisits for physical/functional rehabilitation. Outcomes were measured at the completion of the rehabilitation program (i.e., at 3 months), with cognitive functioning as the primary outcome. Analyses were conducted using linear regression to examine differences in 3-month outcomes between treatment groups while adjusting for baseline scores. RESULTS: Patients tolerated the program with only one adverse event reported. At baseline both groups were well-matched. At 3-month follow-up, intervention group patients demonstrated significantly improved cognitive executive functioning on the widely used and well-normed Tower test (for planning and strategic thinking) vs. controls (median [interquartile range], 13.0 [11.5-14.0] vs. 7.5 [4.0-8.5]; adjusted p < .01). Intervention group patients also reported better performance (i.e., lower score) on one of the most frequently used measures of functional status (Functional Activities Questionnaire at 3 months vs. controls, 1.0 [0.0 3.0] vs. 8.0 [6.0-11.8], adjusted p = .04). CONCLUSIONS: A multicomponent rehabilitation program for intensive care unit survivors combining cognitive, physical, and functional training appears feasible and possibly effective in improving cognitive performance and functional outcomes in just 3 months. Future investigations with a larger sample size should be conducted to build on this pilot feasibility program and to confirm these results, as well as to elucidate the elements of rehabilitation contributing most to improved outcomes. PMID- 22080632 TI - C1-esterase inhibitor infusion increases survival rates for patients with sepsis*. AB - OBJECTIVES: Systemic inflammatory response variability displays differing degrees of organ damage and differing outcomes of sepsis. C1-esterase inhibitor, an endogenous acute-phase protein, regulates various inflammatory and anti inflammatory pathways, including the kallikrein-kinin system and leukocyte activity. This study assesses the influence of high-dose C1-esterase inhibitor administration on systemic inflammatory response and survival in patients with sepsis. DESIGN: Open-label randomized controlled study. SETTING: Surgical and medical intensive care units of nine university and city hospitals. PATIENTS: : Sixty-one patients with sepsis. INTERVENTIONS: Patients were randomized to receive either 12,000 U of C1-esterase inhibitor infusions in addition to conventional treatment or conventional treatment only (n = 41 C1-esterase inhibitor, 20 controls). Blood samples for measurement of C1-esterase inhibitor, complement components C3 and C4, and C-reactive protein concentrations were drawn on days 1, 3, 5, 7, 10, and 28. MEASUREMENTS AND MAIN RESULTS: Quartile analysis of C1-esterase inhibitor activity in sepsis subjects revealed that the lowest quartile subgroup had similar activity levels (0.7-1.2 U/L), when compared to healthy volunteers (p > .05). These normal-level C1-esterase inhibitor sepsis patients nevertheless displayed increased C-reactive protein (p = .04) production and higher likelihoods of a more severe sepsis (p = .001). Overall, infusion of C1-esterase inhibitor increased C1-esterase inhibitor (p < .005 vs. control on days 2, 3, and 5) functional activity, resulted in higher C3 levels (p < .05 vs. control on days 2 and 3), followed by decreased C-reactive protein (p < .05 vs. control on days 3 and 10). Simultaneously, C1-esterase inhibitor infusion in sepsis patients was associated with reduced all-cause mortality (12% vs. 45% in control, p = .008) as well as sepsis-related mortality (8% vs. 45% in control, p = .001) assessed over 28 days. The highest absolute reduction risk of 70% was achieved in sepsis patients with Simplified Acute Physiology Score II scores >27. CONCLUSION: In the present study, patients in the lowest quartile of C1-esterase inhibitor activity in combination with high C-reactive protein demonstrated a higher risk of developing severe sepsis. In general, high-dose C1-esterase inhibitor infusion down-regulated the systemic inflammatory response and was associated with improved survival rates in sepsis patients, which could have important treatment and survival implications for individuals with C1-esterase inhibitor functional deficiency. PMID- 22080633 TI - Clinical outcomes of type III Pseudomonas aeruginosa bacteremia. AB - BACKGROUND: Pseudomonas aeruginosa bacteremia is a serious and life-threatening infection associated with high mortality. Among the multitude of virulence determinants possessed by P. aeruginosa, the type 3 secretion system has been implicated with more acute and invasive infection in respiratory diseases. However, the relationship between the type 3 secretion system and clinical outcomes in P. aeruginosa bacteremia has not been investigated. OBJECTIVES: To determine the association between the type 3 secretion system virulence factor in P. aeruginosa bloodstream infection and 30-day mortality. DESIGN: Retrospective analysis of 85 cases of P. aeruginosa bacteremia. SETTING: Tertiary care hospital. INTERVENTIONS: Bacterial isolates were assayed in vitro for secretion of type 3 exotoxins (ExoU, ExoT, and ExoS). Strain relatedness was analyzed using randomly amplified polymorphic DNA polymerase chain reaction genotyping. Antimicrobial susceptibilities were determined by means of the Kirby-Bauer disk diffusion test. MEASUREMENTS AND MAIN RESULTS: At least one of the type 3 secretion system proteins was detected in 37 out of the 85 isolates (44%). Septic shock was identified in 43% of bacteremic patients with type 3 secretion system+ isolates compared to 23% of patients with type 3 secretion system- isolates (p = .12). A high frequency of resistance in the type 3 secretion system+ isolates was observed to ciprofloxacin (59%), cefepime (35%), and gentamicin (38%). There was a significant difference in the 30-day cumulative probability of death after bacteremia between secretors and nonsecretors (p = .02). None of the type 3 secretion system+ patients who survived the first 30 days had a P. aeruginosa isolate which exhibited ExoU phenotype. CONCLUSIONS: The expression of type 3 secretion system exotoxins in bacteremic isolates of P. aeruginosa confers poor clinical outcomes independent of antibiotic susceptibility profile. PMID- 22080634 TI - A cardiac arrest: when recommended mild therapeutic hypothermia reveals the mechanism*. AB - AIM: Describe the interaction between the use of mild induced hypothermia and acute diffuse coronary spasm. METHODS: We report the case of a 52-yr-old Caucasian woman resuscitated after initial cardiac arrest, with normal postresuscitation electrocardiogram, sufficient hemodynamic conditions, and decreased level of consciousness, who received mild induced hypothermia to reduce brain damage as suggested by cardiopulmonary resuscitation guidelines. RESULTS: After the beginning of mild therapeutic hypothermia, the patient experienced malignant diffuse coronary artery spasm, so-called Prinzmetal's angina, leading to myocardial ischemia and ventricular tachycardia, which was only resolved by intracoronary vasodilator injection. CONCLUSION: Mild induced hypothermia was apparently the trigger of a severe and diffuse coronary artery spasm. PMID- 22080635 TI - The epidemiology of Hajj-related critical illness: lessons for deployment of temporary critical care services*. AB - RATIONAL: The annual Hajj experience has direct relevance for other jurisdictions planning rapid deployment strategies for intensive care for large groups during expected or emergent events. OBJECTIVE: Approximately 2-3 million Muslims from over 160 countries travel to Saudi Arabia each year for Hajj. These pilgrims are typically older adults with a spectrum of comorbid conditions and of various ethnicities. This, coupled with a 2-wk period of physical migration in close contact with others, can lead to acute and critical illness from a variety of infectious and noninfectious causes and a requirement for full-scale but temporary intensive care to a large population. We describe patient characteristics, patterns of disease, and critical illness, including episodes of Influenza A 2009 (H1N1), therapies delivered, and clinical outcomes. METHODS: Prospective cohort study of 110 critically ill patients in four hospitals during the 2009 ("1431": November 18 to December 4) Hajj in Saudi Arabia. MEASUREMENTS AND MAIN RESULTS: Median (interquartile range) age was 60.5 (51.3-70) yrs, 69 (62.7%) were male, and Acute Physiology and Chronic Health Evaluation IV score was 60.5 (47-78.3). Forty-one patients (37.3%) were critically ill due to cardiovascular diseases (23.6% with myocardial infarction); 51 (46.4%) had severe infections (21.8% with H1N1); electrolyte disturbance (21.8%); or pulmonary illness (15.5%). Sixty patients (54.6%) required ventilation. Median predicted mortality by Acute Physiology and Chronic Health Evaluation IV was 14% while actual short-term mortality was 6.4% (p = .009). Longer-term mortality may be higher. CONCLUSION: Both event-specific conditions and patient-specific comorbid conditions are common causes of critical illness during large gatherings. With the ability to provide temporary but full-service intensive care, morbidity and mortality due to critical illness can be low, even among an older patient population and difficult care conditions. PMID- 22080636 TI - Family response to critical illness: postintensive care syndrome-family. AB - BACKGROUND: The family response to critical illness includes development of adverse psychological outcomes such as anxiety, acute stress disorder, posttraumatic stress, depression, and complicated grief. This cluster of complications from exposure to critical care is now entitled postintensive care syndrome-family. Adverse psychological outcomes occur in parents of neonatal and pediatric patients and in family members of adult patients, and may be present for >4 yrs after intensive care unit discharge. Psychological repercussions of critical illness affect the family member's ability to fully engage in necessary care-giving functions after hospitalization. PREVENTION: It has been suggested that the manner in which healthcare workers communicate with family members and the way in which families are included in care and decision-making, may affect long-term outcomes. Preventive strategies for optimal communication and inclusion in care are reviewed. ASSESSMENT: Many tools are available to assess the risk for and to diagnose postintensive care syndrome-family conditions during hospitalization and at intervals after discharge. TREATMENT: Visits after discharge, support groups, and clinics have been proposed for assessing the need for professional referrals as well as for treating family members when psychological illness persists. Studies evaluating these measures are reviewed. PMID- 22080638 TI - Effects of duty cycle and positive end-expiratory pressure on mucus clearance during mechanical ventilation*. AB - OBJECTIVES: During mechanical ventilation, air flows may play a role in mucus transport via two-phase gas liquid flow. The aim of this study was to evaluate effects of duty cycles and positive end-expiratory pressure on mucus clearance in pigs using mechanical ventilation, and to assess their safety. DESIGN: Prospective randomized animal study. SETTING: Animal research facility, University of Barcelona, Spain. SUBJECTS: Eight healthy pigs. INTERVENTIONS: Pigs were intubated and on volume-control mechanical ventilation for up to 84 hrs. After 4, 24, 48, and 72 hrs of mechanical ventilation, six levels of duty cycle (0.26, 0.33, 0.41, 0.50, 0.60, and 0.75) with no associated positive end expiratory pressure or 5 cm H2O of positive end-expiratory pressure were randomly applied. Surgical bed was oriented 30 degrees in the reverse Trendelenburg position, as in the semirecumbent position. MEASUREMENT AND MAIN RESULTS: Inspiratory and expiratory flows and hemodynamics were measured after each 30-min ventilation period. Mucus movement was assessed through fluoroscopy tracking of radio-opaque markers. Mucus velocity was described by a positive vector (toward the glottis) or negative vector (toward the lungs). No effect of positive end expiratory pressure was found; however, as duty cycle was increasingly prolonged, a trend toward reduced velocity of mucus moving toward the lungs and increased outward mucus velocity was found (p = .064). Two clusters of mucus velocities were identified as duty cycle was prolonged beyond 0.41. Thus, duty cycle >0.41 increased mean expiratory-inspiratory flow bias from -4.1 +/- 4.6 to 7.9 +/- 5.9 L/min (p < .0001) and promoted outward mucus velocity from -0.22 +/- 1.71 mm/min (range, -5.78 to 2.42) to 0.53 +/- 1.06 mm/min (-1.91 to 3.88; p = .0048). Duty cycle of 0.75 resulted in intrinsic positive end-expiratory pressure (2.1 +/- 1.1 cm H2O [p < .0001] vs. duty cycle 0.26-0.5), with no hemodynamic compromise. CONCLUSIONS: In the semirecumbent position, mucus clearance is improved with prolongation of the duty cycle. However, in clinical practice, positive findings must be balanced against the potentially adverse hemodynamic and respiratory effects. PMID- 22080637 TI - The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*. AB - OBJECTIVES: Plasma tryptophan levels are associated with delirium in critically ill patients. Although tryptophan has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) remains unknown. This study examined the association between kynurenine pathway activity as determined by plasma kynurenine concentrations and kynurenine/tryptophan ratios and presence or absence of acute brain dysfunction (defined as delirium/coma-free days) in intensive care unit patients. DESIGN, SETTING, AND PATIENTS: This was a prospective cohort study that utilized patient data and blood samples from the Maximizing Efficacy of Targeted Sedation and Reducing Neurologic Dysfunction trial, which compared sedation with dexmedetomidine vs. lorazepam in mechanically ventilated patients. MEASUREMENTS AND MAIN RESULTS: Baseline plasma kynurenine and tryptophan concentrations were measured using high-performance liquid chromatography with or without tandem mass spectrometry. Delirium was assessed daily using the Confusion Assessment Method for the Intensive Care Unit. Linear regression examined associations between kynurenine pathway activity and delirium/coma-free days after adjusting for sedative exposure, age, and severity of illness. Among 84 patients studied, median age was 60 yrs and Acute Physiology and Chronic Health Evaluation II score was 28.5. Elevated plasma kynurenine and kynurenine/tryptophan ratio were both independently associated with significantly fewer delirium/coma-free days (i.e., fewer days without acute brain dysfunction). Specifically, patients with plasma kynurenine or kynurenine/tryptophan ratios at the 75th percentile of our population had an average of 1.8 (95% confidence interval 0.6-3.1) and 2.1 (95% confidence interval 1.0-3.2) fewer delirium/coma free days than those patients with values at the 25th percentile (p = .006 and p < .001, respectively). CONCLUSIONS: Increased kynurenine pathway activation, assessed by plasma kynurenine and kynurenine/tryptophan ratio, was associated with fewer days alive and without acute brain dysfunction in intensive care unit patients. Future studies are warranted to clarify this relationship and investigate potential therapeutic interventions. PMID- 22080639 TI - Predictors of pulmonary edema formation during fluid loading in the critically ill with presumed hypovolemia*. AB - OBJECTIVES: It is largely unknown why extravascular lung water may increase during fluid loading in the critically ill with presumed hypovolemia. In this study we evaluated the hemodynamic predictors of such an increase. DESIGN: A prospective observational study. PATIENTS: Sixty-three presumed hypovolemic mechanically ventilated patients (22 septic and 41 nonseptic patients). INTERVENTION: Fluid loading with saline or colloid fluids guided by (changes in) cardiac filling pressures. MEASUREMENTS AND MAIN RESULTS: Before and after fluid loading, hemodynamic and respiratory variables were recorded, including variables obtained by transpulmonary dilution such as cardiac index, pulmonary blood volume index, and extravascular lung water. Baseline parameters and change in parameters were compared between patients with a change in extravascular lung water <10% and patients with a change in extravascular lung water >= 10%. Predictive values for change in extravascular lung water >= 10% were evaluated. Baseline cardiac index and pulmonary blood volume index were higher, whereas change in cardiac index, change in pulmonary blood volume index, and change in PaO2/FIO2 ratio were lower in patients with a change in extravascular lung water >= 10% than in patients with a change in extravascular lung water <10%. The change in extravascular lung water correlated to baseline cardiac index (r = 0.17; p = .001), baseline pulmonary blood volume index (r = 0.15; p = .001), change in pulmonary blood volume index (r = 0.16; p < .001), and change in PaO2/FIO2 ratio (r = 0.13; p = .004). In multiple logistic regression analysis baseline cardiac index, baseline pulmonary blood volume index, the change in cardiac index, change in pulmonary blood volume index, and change in PaO2/FIO2 ratio individually contributed to prediction of a change in extravascular lung water >= 10%, independent of the presence of sepsis, pulmonary vascular permeability, and cardiac filling pressures. A change in extravascular lung water >= 10% was predicted by baseline cardiac index (77% sensitivity, 98% specificity) and pulmonary blood volume index (92% sensitivity, 68% specificity), and by change in cardiac index (69% sensitivity, 59% specificity), change in pulmonary blood volume index (77% sensitivity, 82% specificity), and change in PaO2/FIO2 ratio (77% sensitivity, 66% specificity). CONCLUSION: Extravascular lung water increase during fluid loading in the critically ill is predicted by a plateau of cardiac function and pulmonary vascular filling at baseline, rather than by pulmonary vascular permeability and filling pressures. Increasing extravascular lung water is further reflected by a decrease of PaO2/FIO2 ratio. These observations may help preventing pulmonary fluid overloading. PMID- 22080640 TI - Mortality and intensive care volume in ventilated patients from 1995 to 2009 in the Australian and New Zealand binational adult patient intensive care database*. AB - OBJECTIVES: The mortality outcome of mechanical ventilation, a key intervention in the critically ill, has been variously reported to be determined by intensive care patient volume. We determined the volume-(mortality)-outcome relationship of mechanically ventilated patients whose records were contributed to the Australian and New Zealand Intensive Care Society Adult Patient Database. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 208,810 index patient admissions from 136 Australian and New Zealand intensive care units in the same number of hospitals over the course of 1995-2009. MEASUREMENTS AND MAIN RESULTS: The patient-volume effect on hospital mortality, overall and at the level of patient (nonsurgical, elective surgical, and emergency surgical) and intensive care unit (rural/regional, metropolitan, tertiary, and private) descriptors, was determined by random-effects logistic regression adjusting for illness severity and demographic and geographical predictors. Annualized patient volume was modeled both as a categorical (deciles) and, with calendar year, a continuous variable using fractional polynomials. The patients were of mean age of 59 yrs (SD, 19 yrs), Acute Physiology and Chronic Health Evaluation III score 66 (32), and 39.4% female, with a hospital mortality of 22.4%. Overall and at both the patient and intensive care unit descriptor levels, no progressive decline in mortality was demonstrated across the annual patient volume range (12-932). Over the whole database, mortality odds ratio for the last volume decile (801-932 patients) was 1.26 (95% confidence interval, 1.06-1.50; p = .009) compared with the first volume decile (12-101 patients). Calendar year mortality decreases were evident (odds ratio, 0.96; 95% confidence interval, 0.94-0.98; p = .0001). Using fractional polynomials, modest curvilinear mortality increases (range, 5%-8%) across the volume range were noted over the whole database for nonsurgical patients and at the tertiary intensive care unit level. CONCLUSION: No inverse volume-(mortality)-outcome relationship was apparent for ventilated patients in the Australian and New Zealand Intensive Care Society database. Mechanisms for mortality increments with patient volume were not identified but warrant further study. PMID- 22080641 TI - Nuclear factor-kappaB signaling contributes to mechanical ventilation-induced diaphragm weakness*. AB - OBJECTIVES: Although mechanical ventilation is a life-saving measure for patients in respiratory failure, prolonged mechanical ventilation results in diaphragmatic weakness attributable to fiber atrophy and contractile dysfunction. Therefore, identifying the signaling pathways responsible for mechanical ventilation-induced diaphragmatic weakness is important. In this context, it is established that oxidative stress is required for mechanical ventilation-induced diaphragmatic weakness to occur. Numerous redox-sensitive signaling pathways exist in muscle including the transcription factor nuclear factor-kappaB. Although it has been suggested that nuclear factor-kappaB contributes to proteolytic signaling in inactivity-induced atrophy in locomotor muscles, the role that nuclear factor kappaB plays in mechanical ventilation-induced diaphragmatic weakness is unknown. We tested the hypothesis that nuclear factor-kappaB activation plays a key signaling role in mechanical ventilation-induced diaphragmatic weakness and that oxidative stress is required for nuclear factor-kappaB activation. DESIGN: Cause and effect was determined by independently treating mechanically ventilated animals with either a specific nuclear factor-kappaB inhibitor (SN50) or a clinically relevant antioxidant (curcumin). MEASUREMENTS AND MAIN RESULTS: Inhibition of nuclear factor-kappaB activity partially attenuated both mechanical ventilation-induced diaphragmatic atrophy and contractile dysfunction. Further, treatment with the antioxidant curcumin prevented mechanical ventilation-induced activation of nuclear factor-kappaB in the diaphragm and rescued the diaphragm from both mechanical ventilation-induced atrophy and contractile dysfunction. CONCLUSIONS: Collectively, these findings support the hypothesis that nuclear factor-kappaB activation plays a significant signaling role in mechanical ventilation-induced diaphragmatic weakness and that oxidative stress is an upstream activator of nuclear factor-kappaB. Finally, our results suggest that prevention of mechanical ventilation-induced oxidative stress in the diaphragm could be a useful clinical strategy to prevent or delay mechanical ventilation induced diaphragmatic weakness. PMID- 22080642 TI - Tissue factor/factor VIIa pathway mediates coagulation activation in induced-heat stroke in the baboon. AB - OBJECTIVE: Excessive activation of coagulation, which can culminate in overt disseminated intravascular coagulation, is a prominent feature of heat stroke. However, neither the mechanism that initiates the coagulation activation nor its pathogenic role is known. We examined whether the tissue factor/factor VIIa complex initiates the coagulation activation in heat stroke and, if so, whether upstream inhibition of coagulation activation through its neutralization may minimize cellular injury and organ dysfunction. We also examined whether coagulation inhibition influences heat stroke-induced fibrinolytic and inflammatory responses. DESIGN: Randomized controlled study. SETTING: Comparative Medicine Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. SUBJECTS: Baboons (Papio Hamadryas). INTERVENTIONS: Twelve anesthetized baboons assigned randomly to recombinant nematode anticoagulant protein c2, a powerful inhibitor of tissue factor/factor VIIa-dependent coagulation (n = 6), or a control group (n = 6) were heat-stressed in a prewarmed neonatal incubator at 44-47 degrees C until systolic blood pressure fell <90 mm Hg, signaling the onset of severe heat stroke. Recombinant nematode anticoagulant protein c2 was administered as a single intravenous dose of 30 MUg/kg body weight at onset of heat stroke. The control group received an equivalent volume of sterile saline intravenously. MEASUREMENTS AND MAIN RESULTS: Heat stroke was associated with coagulation activation and fibrin formation as evidenced by the increased plasma thrombin-antithrombin complexes, endogenous thrombin potential, and D-dimer levels. Recombinant nematode anticoagulant protein c2 induced significant inhibition of thrombin generation and fibrin formation. Inhibition of coagulation in recombinant nematode anticoagulant protein c2-treated animals did not influence either fibrinolysis (assessed by tissue plasminogen activator, plasmin-alpha2-antiplasmin complexes, and plasminogen activator inhibitor) or the release of pro- and anti-inflammatory cytokines. No difference in markers of cell injury and organ dysfunction was observed between recombinant nematode anticoagulant protein c2-treated and control groups. CONCLUSIONS: Tissue factor/factor VIIa-dependent pathway initiates coagulation activation in induced heat stroke in the baboon without an effect on fibrinolysis and inflammation. The findings suggest also that coagulation activation is not a prerequisite of cell injury and organ dysfunction. PMID- 22080643 TI - A multicenter mortality prediction model for patients receiving prolonged mechanical ventilation. AB - OBJECTIVE: Significant deficiencies exist in the communication of prognosis for patients requiring prolonged mechanical ventilation after acute illness, in part because of clinician uncertainty about long-term outcomes. We sought to refine a mortality prediction model for patients requiring prolonged ventilation using a multicentered study design. DESIGN: Cohort study. SETTING: Five geographically diverse tertiary care medical centers in the United States (California, Colorado, North Carolina, Pennsylvania, and Washington). PATIENTS: Two hundred sixty adult patients who received at least 21 days of mechanical ventilation after acute illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the probability model, we included age, platelet count, and requirement for vasopressors and/or hemodialysis, each measured on day 21 of mechanical ventilation, in a logistic regression model with 1-yr mortality as the outcome variable. We subsequently modified a simplified prognostic scoring rule (ProVent score) by categorizing the risk variables (age 18-49, 50-64, and >=65 yrs; platelet count 0-150 and >150; vasopressors; hemodialysis) in another logistic regression model and assigning points to variables according to beta coefficient values. Overall mortality at 1 yr was 48%. The area under the curve of the receiver operator characteristic curve for the primary ProVent probability model was 0.79 (95% confidence interval 0.75-0.81), and the p value for the Hosmer-Lemeshow goodness-of-fit statistic was .89. The area under the curve for the categorical model was 0.77, and the p value for the goodness-of-fit statistic was .34. The area under the curve for the ProVent score was 0.76, and the p value for the Hosmer-Lemeshow goodness-of-fit statistic was .60. For the 50 patients with a ProVent score >2, only one patient was able to be discharged directly home, and 1-yr mortality was 86%. CONCLUSION: The ProVent probability model is a simple and reproducible model that can accurately identify patients requiring prolonged mechanical ventilation who are at high risk of 1-yr mortality. PMID- 22080644 TI - Integrating palliative care in the surgical and trauma intensive care unit: a report from the Improving Palliative Care in the Intensive Care Unit (IPAL-ICU) Project Advisory Board and the Center to Advance Palliative Care. AB - OBJECTIVE: Although successful models for palliative care delivery and quality improvement in the intensive care unit have been described, their applicability in surgical intensive care unit settings has not been fully addressed. We undertook to define specific challenges, strategies, and solutions for integration of palliative care in the surgical intensive care unit. DATA SOURCES: We searched the MEDLINE database from inception to May 2011 for all English language articles using the term "surgical palliative care" or the terms "surgical critical care," "surgical ICU," "surgeon," "trauma" or "transplant," and "palliative care" or "end-of- life care" and hand-searched our personal files for additional articles. Based on review of these articles and the experiences of our interdisciplinary expert Advisory Board, we prepared this report. DATA EXTRACTION AND SYNTHESIS: We critically reviewed the existing literature on delivery of palliative care in the surgical intensive care unit setting focusing on challenges, strategies, models, and interventions to promote effective integration of palliative care for patients receiving surgical critical care and their families. CONCLUSIONS: Characteristics of patients with surgical disease and practices, attitudes, and interactions of different disciplines on the surgical critical care team present distinctive issues for intensive care unit palliative care integration and improvement. Physicians, nurses, and other team members in surgery, critical care and palliative care (if available) should be engaged collaboratively to identify challenges and develop strategies. "Consultative," "integrative," and combined models can be used to improve intensive care unit palliative care, although optimal use of trigger criteria for palliative care consultation has not yet been demonstrated. Important components of an improvement effort include attention to efficient work systems and practical tools and to attitudinal factors and "culture" in the unit and institution. Approaches that emphasize delivery of palliative care together with surgical critical care hold promise to better integrate palliative care into the surgical intensive care unit. PMID- 22080645 TI - Critical care physicians' approaches to negotiating with surrogate decision makers: a qualitative study. AB - OBJECTIVE: To describe how critical care physicians manage conflicts with surrogates about withdrawing or withholding patients' life support. DESIGN: Qualitative analysis of key informant interviews with critical care physicians during 2010. We transcribed interviews verbatim and used grounded theory to code and revise a taxonomy of themes and to identify illustrative quotes. SETTING: Three academic medical centers, one academic-affiliated medical center, and four private practice groups or private hospitals in a large Midwestern city SUBJECTS: Fourteen critical care physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physicians reported tailoring their approach to address specific reasons for disagreement with surrogates. Five common approaches were identified: 1) building trust; 2) educating and informing; 3) providing surrogates more time; 4) adjusting surrogate and physician roles; and 5) highlighting specific values. When mistrust was an issue, physicians endeavored to build a more trusting relationship with the surrogate before readdressing decision making. Physicians also reported correcting misunderstandings by providing targeted education, and some reported highlighting specific patient, surrogate, or physician values that they hoped would guide surrogates to agree with them. When surrogates struggled with decisionmaking roles, physicians attempted to reinforce the concept of substituted judgment. Physicians noted that some surrogates needed time to "come to terms" with the patent's illness before agreeing with physicians. Many physicians had witnessed colleagues negotiate in ways they found objectionable such as providing misleading information, injecting their own values into the negotiation or behaving unprofessionally toward surrogates. Although some physicians viewed their efforts to encourage surrogates' agreement as persuasive, others strongly denied persuading surrogates and described their actions as "guiding" or "negotiating." CONCLUSIONS: Physicians reported using a tailored approach to resolve decisional conflicts about life support and attempted to change surrogates' decisions in accordance with what the physician thought was in the patients' best interests. Although physicians acknowledged their efforts to change surrogates' decisions, many physicians did not perceive these efforts as persuasive. PMID- 22080646 TI - Intracellular GSH and ascorbate inhibit radical-induced protein chain peroxidation in HL-60 cells. AB - The results of this study suggest that the well-documented loss of GSH and ascorbate in organisms under oxidative stress may be mainly due to their reactions with protein radicals and/or peroxides. Protein hydroperoxides were generated in HL-60 cells exposed to radiation-generated hydroxyl radicals. We found for the first time evidence of chain peroxidation of the proteins in cells, with each hydroxyl radical leading to the formation of about 10 hydroperoxides. Protein peroxidation showed a lag, probably due to the endogenous antioxidant enzymes, with simultaneous loss of the intracellular GSH. Enhancement of the GSH levels by N-acetylcysteine decreased the formation of hydroperoxides, while treatment with l-buthionine sulfoximine had the opposite effect. The effect of variation of GSH levels on the formation of the peroxidized proteins is explained primarily by reduction of the protein hydroperoxides by GSH. Loading of the cells with ascorbate resulted in reduction of the amounts of protein hydroperoxides generated by the radiation, which was proportional to the intracellular ascorbate concentration. In contrast to the GSH, inhibition of protein hydroperoxide formation in the presence of the high (mM) intracellular ascorbate levels achieved was mainly due to the direct scavenging of hydroxyl radicals by the vitamin. PMID- 22080647 TI - Uses and misuses of statistics: the case of strontium ranelate and the number needed to treat. AB - In the last 15 years, several pharmacological agents for the prevention of fractures have been developed and commercialized. Most of them showed to be effective in reducing fracture risk. The enhanced availability of drugs to prevent fractures has generated a fierce competition among pharmaceutical companies to conquer a share of the potential market, often with claims of superiority of a drug over another without direct comparisons. The definitive way to compare different treatments would require randomized head to head trials. These trials are expensive, need large samples and are unlikely to be ever performed. Therefore, it has become a common practice to compare pharmacological agents through observational studies on administrative databases or by the indirect comparison of the results of individual randomised-controlled trials (RCT) and their meta-analyses. These studies may produce evidence of clinical value, complementary to that given by RCT. However, without a proper and complete analysis, they may result in a biased picture of effectiveness and be completely misleading. In this article, we critically disclose how such competition may produce biased and misleading picture of evidence, by reviewing the significance of the number needed to treat, absolute risk reduction and relative risk reduction in relation to vertebral fractures prevention with available drugs. PMID- 22080648 TI - A case of primary retroperitoneal teratoma presenting as an adrenal incidentaloma. PMID- 22080649 TI - Increased intima media thickness at many arterial sites in obese adolescents with abdominal adiposity, insulin resistance, and high LDL-cholesterol. PMID- 22080650 TI - Scleredema adultorum: quali-quantitative analysis of collagen fibers. PMID- 22080651 TI - Endocrinology and art. Hermaphrodite - archeological museum of Istanbul - Turkey. PMID- 22080652 TI - Transmission of 2009 pandemic influenza A (H1N1) virus among healthcare personnel Southern California, 2009. AB - OBJECTIVE: In April 2009, 2009 pandemic influenza A (H1N1) (hereafter, pH1N1) virus was identified in California, which caused widespread illness throughout the United States. We evaluated pH1N1 transmission among exposed healthcare personnel (HCP) and assessed the use and effectiveness of personal protective equipment (PPE) early in the outbreak. DESIGN: Cohort study. SETTING: Two hospitals and 1 outpatient clinic in Southern California during March 28-April 24, 2009. PARTICIPANTS: Sixty-three HCP exposed to 6 of the first 8 cases of laboratory-confirmed pH1N1 in the United States. METHODS: Baseline and follow-up questionnaires were used to collect demographic, epidemiologic, and clinical data. Paired serum samples were obtained to test for pH1N1-specific antibodies by microneutralization and hemagglutination-inhibition assays. Serology results were compared with HCP work setting, role, and self-reported PPE use. RESULTS: Possible healthcare-associated pH1N1 transmission was identified in 9 (14%) of 63 exposed HCP; 6 (67%) of 9 seropositive HCP had asymptomatic infection. The highest attack rates occurred among outpatient HCP (6/19 [32%]) and among allied health staff (eg, technicians; 8/33 [24%]). Use of mask or N95 respirator was associated with remaining seronegative (P = .047). Adherence to PPE recommendations for preventing transmission of influenza virus and other respiratory pathogens was inadequate, particularly in outpatient settings. CONCLUSIONS: pH1N1 transmission likely occurred in healthcare settings early in the pandemic associated with inadequate PPE use. Organizational support for a comprehensive approach to infectious hazards, including infection prevention training for inpatient- and outpatient-based HCP, is essential to improve HCP and patient safety. PMID- 22080653 TI - A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel. AB - OBJECTIVE: To devise a local strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). DESIGN: Quasi experimental, before-and-after, interrupted time-series study. SETTING: A 1,000 bed tertiary-care university teaching hospital. METHODS: Retrospectively, all relevant data were collected from the medical records of patients with CRKP infections from May 2006 through April 2007, the preintervention period. From May 1, 2007, through May 1, 2010, the postintervention period, the intervention was applied and prospectively followed. The 5 key elements of this strategy were an emergency department flagging system, the building of a cohort ward, the eradication of clusters, environmental and personnel hand cultures, and a carbapenem-restriction policy. The demographic and clinical parameters of patients colonized by and/or infected with CRKP were collected from medical records. RESULTS: A total of 10,680 rectal cultures were performed for 8,376 patients; 433 (5.16%) and 370 (4.4%) were CRKP-colonized and CRKP-infected patients, respectively, and 789 (98%) of 803 patients were admitted to the CRKP cohort ward. The CRKP infection density was reduced from 5.26 to 0.18 per 10,000 patient-days (P <= .001), and no nosocomial CRKP infections were diagnosed. Twenty-three percent of environmental cultures were found to be positive. Meropenem use was reduced from 283 +/- 70.92 to 118 +/- 74.32 defined daily doses per 1,000 patient-days (P <= .001). CONCLUSION: This intervention produced an enormous impact on patient location, surveillance cultures, and antibiotic policies and a massive investment in infection control resources. PMID- 22080654 TI - Use of adherence monitors as part of a team approach to control clonal spread of multidrug-resistant Acinetobacter baumannii in a research hospital. AB - BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MDRAB) is difficult to treat and eradicate. Several reports describe isolation and environmental cleaning strategies that controlled hospital MDRAB outbreaks. Such interventions were insufficient to interrupt MDRAB transmission in 2 intensive care unit-based outbreaks in our hospital. We describe strategies that were associated with termination of MDRAB outbreaks at the National Institutes of Health Clinical Center. METHODS: In response to MDRAB outbreaks in 2007 and 2009, we implemented multiple interventions, including stakeholder meetings, enhanced isolation precautions, active microbial surveillance, cohorting, and extensive environmental cleaning. We conducted a case-control study to analyze risk factors for acquiring MDRAB. In each outbreak, infection control adherence monitors were placed in MDRAB cohort areas to observe and correct staff infection control behavior. RESULTS: Between May 2007 and December 2009, 63 patients acquired nosocomial MDRAB; 57 (90%) acquired 1 or more of 4 outbreak strains. Of 347 environmental cultures, only 2 grew outbreak strains of MDRAB from areas other than MDRAB patient rooms. Adherence monitors recorded 1,330 isolation room entries in 2007, of which 8% required interventions. In 2009, around-the-clock monitors recorded 4,892 staff observations, including 127 (2.6%) instances of nonadherence with precautions, requiring 68 interventions (1.4%). Physicians were responsible for more violations than other staff (58% of hand hygiene violations and 37% of violations relating to gown and glove use). Each outbreak terminated in temporal association with initiation of adherence monitoring. CONCLUSIONS: Although labor intensive, adherence monitoring may be useful as part of a multifaceted strategy to limit nosocomial transmission of MDRAB. PMID- 22080655 TI - Emergence of glutaraldehyde-resistant Pseudomonas aeruginosa. AB - OBJECTIVE: In November 2009, routine sampling of endoscopes performed to monitor the effectiveness of the endoscope-cleaning procedure at our hospital detected Pseudomonas aeruginosa. Herein we report the results of the subsequent investigation. DESIGN AND METHODS: The investigation included environmental cultures for source investigation, molecular analysis by pulsed-field gel electrophoresis (PFGE) to reveal the identity of the strains, and determination of the bactericidal activity of the glutaraldehyde-based disinfectant used for automated endoscope reprocessing. In addition, patient outcome was analyzed by medical chart review, and incidence rates of clinical samples with P. aeruginosa were compared. SETTING: The University Hospital of Basel is an 855-bed tertiary care center in Basel, Switzerland. Approximately 1,700 flexible bronchoscopic, 2,500 gastroscopic, 1,400 colonoscopic, 140 endoscopic retrograde cholangiopancreatographic, and 140 endosonographic procedures are performed annually. RESULTS: P. aeruginosa was detected in samples obtained from endoscopes in November 2009 for the first time since the initiation of surveillance in 2006. It was found in the rinsing water and in the drain of 1 of the 2 automated endoscope reprocessors. PFGE revealed 2 distinct P. aeruginosa strains, one in each reprocessor. The glutaraldehyde-based disinfectant showed no activity against the 2 pseudo-outbreak strains when used in the recommended concentration under standard conditions. After medical chart review, 6 patients with lower respiratory tract and bloodstream infections were identified as having a possible epidemiological link to the pseudo-outbreak strain. CONCLUSIONS: This is the first description of a pseudo-outbreak caused by P. aeruginosa with reduced susceptibility to an aldehyde-based disinfectant routinely used in the automated processing of endoscopes. PMID- 22080656 TI - Outbreak of Pseudomonas aeruginosa surgical site infections after arthroscopic procedures: Texas, 2009. AB - SETTING: Seven organ/space surgical site infections (SSIs) that occurred after arthroscopic procedures and were due to Pseudomonas aeruginosa of indistinguishable pulsed-field gel electrophoresis (PFGE) patterns occurred at hospital X in Texas from April 22, 2009, through May 7, 2009. OBJECTIVE: To determine the source of the outbreak and prevent future infections. DESIGN: Infection control observations and a case-control study. METHODS: Laboratory records were reviewed for case finding. A case-control study was conducted. A case patient was defined as someone who underwent knee or shoulder arthroscopy at hospital X during the outbreak period and subsequently developed organ/space SSI due to P. aeruginosa. Cultures of environmental and surgical equipment samples were performed, and selected isolates were analyzed by PFGE. Surgical instrument reprocessing practices were reviewed, and surgical instrument lumens were inspected with a borescope after reprocessing to assess cleanliness. RESULTS: The case-control study did not identify any significant patient-related or operator related risk factors. P. aeruginosa grew from 62 of 388 environmental samples. An isolate from the gross decontamination sink had a PFGE pattern that was indistinguishable from that of the case patient isolates. All surgical instrument cultures showed no growth. Endoscopic evaluation of reprocessed arthroscopic equipment revealed retained tissue in the lumen of both the inflow/outflow cannulae and arthroscopic shaver handpiece. No additional cases occurred after changes in instrument reprocessing protocols were implemented. After this outbreak, the US Food and Drug Administration released a safety alert about the concern regarding retained tissue within arthroscopic shavers. CONCLUSIONS: These SSIs were likely related to surgical instrument contamination with P. aeruginosa during instrument reprocessing. Retained tissue in inflow/outflow cannulae and shaver handpieces could have allowed bacteria to survive sterilization procedures. PMID- 22080657 TI - Comparison of fluorescent marker systems with 2 quantitative methods of assessing terminal cleaning practices. AB - OBJECTIVE: To compare fluorescent markers with aerobic colony counts (ACCs) and an adenosine triphosphate (ATP) bioluminescence assay system for assessing terminal cleaning practices. DESIGN: A prospective observational survey. SETTING: A 500-bed university-affiliated community teaching hospital. METHODS: In a convenience sample of 100 hospital rooms, 5 high-touch surfaces were marked with fluorescent markers before terminal cleaning and checked after cleaning to see whether the marker had been entirely or partially removed. ACC and ATP readings were performed on the same surfaces before and after terminal cleaning. RESULTS: Overall, 378 (76%) of 500 surfaces were classified as having been cleaned according to fluorescent markers, compared with 384 (77%) according to ACC criteria and 225 (45%) according to ATP criteria. Of 382 surfaces classified as not clean according to ATP criteria before terminal cleaning, those with the marker removed were significantly more likely than those with the marker partially removed to be classified as clean according to ATP criteria (P = .003). CONCLUSIONS: Fluorescent markers are useful in determining how frequently high touch surfaces are wiped during terminal cleaning. However, contaminated surfaces classified as clean according to fluorescent marker criteria after terminal cleaning were significantly less likely to be classified as clean according to ACC and ATP assays. PMID- 22080658 TI - "The dirty hand in the latex glove": a study of hand hygiene compliance when gloves are worn. AB - BACKGROUND AND OBJECTIVE: Wearing of gloves reduces transmission of organisms by healthcare workers' hands but is not a substitute for hand hygiene. Results of previous studies have varied as to whether hand hygiene is worse when gloves are worn. Most studies have been small and used nonstandardized assessments of glove use and hand hygiene. We sought to observe whether gloves were worn when appropriate and whether hand hygiene compliance differed when gloves were worn. DESIGN: Observational study. PARTICIPANTS AND SETTING: Healthcare workers in 56 medical or care of the elderly wards and intensive care units in 15 hospitals across England and Wales. METHODS: We observed hand hygiene and glove usage (7,578 moments for hand hygiene) during 249 one-hour sessions. Observers also recorded whether gloves were or were not worn for individual contacts. RESULTS: Gloves were used in 1,983 (26.2%) of the 7,578 moments for hand hygiene and in 551 (16.7%) of 3,292 low-risk contacts; gloves were not used in 141 (21.1%) of 669 high-risk contacts. The rate of hand hygiene compliance with glove use was 41.4% (415 of 1,002 moments), and the rate without glove use was 50.0% (1,344 of 2,686 moments). After adjusting for ward, healthcare worker type, contact risk level, and whether the hand hygiene opportunity occurred before or after a patient contact, glove use was strongly associated with lower levels of hand hygiene (adjusted odds ratio, 0.65 [95% confidence interval, 0.54-0.79]; P < .0001). CONCLUSION: The rate of glove usage is lower than previously reported. Gloves are often worn when not indicated and vice versa. The rate of compliance with hand hygiene was significantly lower when gloves were worn. Hand hygiene campaigns should consider placing greater emphasis on the World Health Organization indications for gloving and associated hand hygiene. TRIAL REGISTRATION: National Research Register N0256159318. PMID- 22080659 TI - Epidemiology of central line-associated bloodstream infections in the pediatric intensive care unit. AB - OBJECTIVE: Describe central line-associated bloodstream infection (CLA-BSI) epidemiology in pediatric intensive care units (PICUs). DESIGN: Descriptive study (29 PICUs); cohort study (18 PICUs). SETTING: PICUs in a national improvement collaborative. PATIENTS/PARTICIPANTS: Patients admitted October 2006 to December 2007 with 1 or more central lines. METHODS: CLA-BSIs were prospectively identified using the National Healthcare Safety Network definition and then readjudicated using the revised 2008 definition. Risk factors for CLA-BSI were examined using age-adjusted, time-varying Cox proportional hazards models. RESULTS: In the descriptive study, the CLA-BSI incidence was 3.1/1,000 central line-days; readjudication with the revised definition resulted in a 17% decrease. In the cohort study, the readjudicated incidence was 2.0/1,000 central line-days. Ninety-nine percent of patients were CLA-BSI-free through day 7, after which the daily risk of CLA-BSI doubled to 0.27% per day. Compared with patients with respiratory diagnoses (most prevalent category), CLA-BSI risk was higher in patients with gastrointestinal diagnoses (hazard ratio [HR], 2.7 [95% confidence interval {CI}, 1.43-5.16]; P < .002 ) and oncologic diagnoses (HR, 2.6 [CI, 1.06 6.45]; P = .037). Among all patients, including those with more than 1 central line, CLA-BSI risk was lower among patients with a central line inserted in the jugular vein (HR, 0.43 [CI, 0.30-0.95]; [P < .03). CONCLUSIONS: The 2008 CLA-BSI definition change decreased the measured incidence. The daily CLA-BSI risk was very low in patients during the first 7 days of catheterization but doubled thereafter. The risk of CLA-BSI was lower in patients with lines inserted in the jugular vein and higher in patients with gastrointestinal and oncologic diagnoses. These patients are target populations for additional study and intervention. PMID- 22080660 TI - US hospital requirements for pertussis vaccination of healthcare personnel, 2011. AB - In 2011, institutional requirements for pertussis vaccination of healthcare personnel were reported by nearly one-third of surveyed US hospitals. Requirements often applied to personnel with certain clinical responsibilities, such as those caring for infants. Healthcare personnel who were not on an institution's payroll were rarely subject to pertussis vaccination requirements. PMID- 22080661 TI - Validation of administrative population-based data sets for the detection of cesarean delivery surgical site infection. AB - We validated population-based hospital, emergency room, and physician claim databases for the detection of surgical site infections against the reference standard of clinical surveillance. Although these data sets are highly specific and could be used to define research cohorts, their low sensitivity and positive predictive value make them inadequate for use as quality indicators. PMID- 22080662 TI - A real-life snapshot of the use and abuse of urinary catheters on general medical wards. AB - An observational study was performed on 2 wards in a tertiary hospital to determine staff awareness, knowledge, and documentation of catheter use and the effects these have on duration of catheterization. Overall, there was poor knowledge of the indications and date of catheterization. Doctor awareness decreases duration of catheterization. PMID- 22080663 TI - Web-based training improves knowledge about central line bloodstream infections. AB - A Web-based training course with embedded video clips for reducing central line associated bloodstream infections (CLABSIs) was evaluated and shown to improve clinician knowledge and retention of knowledge over time. To our knowledge, this is the first study to evaluate Web-based CLABSI training as a stand-alone intervention. PMID- 22080664 TI - Surveillance of overall hospital antibiotic consumption: is stratification according to hospital size the best method? PMID- 22080665 TI - Discordance in colonizing strains of Staphylococcus aureus isolated from different body sites. PMID- 22080666 TI - Methicillin-resistant Staphylococcus aureus strain USA300 is prevalent among hospital-onset cases in an urban Canadian setting. PMID- 22080667 TI - Staphylococcus aureus bacteremia and peripheral vascular catheters. PMID- 22080669 TI - Public reporting of Clostridium difficile and improvements in diagnostic tests. PMID- 22080670 TI - Decreasing the prevalence of Clostridium difficile in a long-term care facility. PMID- 22080672 TI - The influenza A/H1N1 pandemic in Southern Brazil. PMID- 22080675 TI - From mixed valence to the Kondo lattice regime. AB - Many heavy fermion materials are known to cross over from the Kondo lattice regime to the mixed valence regime or vice versa as a function of pressure or doping. We study this crossover theoretically by employing the periodic Anderson model within the framework of the dynamical mean field theory. Changes occurring in the dynamics and transport across this crossover are highlighted. As the valence is decreased (increased) relative to the Kondo lattice regime, the Kondo resonance broadens significantly, while the lower (upper) Hubbard band moves closer to the Fermi level. The resistivity develops a two peak structure in the mixed valence regime: a low temperature coherence peak and a high temperature 'Hubbard band' peak. These two peaks merge, yielding a broad shallow maximum upon decreasing the valence further. The optical conductivity likewise exhibits an unusual absorption feature (shoulder) in the deep mid-infrared region, which grows in intensity with decreasing valence. The involvement of the Hubbard bands in dc transport and of the effective f-level in the optical conductivity are shown to be responsible for the anomalous transport properties. A two-band hybridization-gap model, which neglects incoherent effects due to many-body scattering, commonly employed to understand the optical response in these materials is shown to be inadequate, especially in the mixed valence regime. Comparison of theory with experiment carried out for (a) dc resistivities of CeRhIn(5), Ce(2)Ni(3)Si(5), CeFeGe(3) and YbIr(2)Si(2), (b) pressure dependent resistivity of YbInAu(2) and CeCu(6), and (c) optical conductivity measurements in YbIr(2)Si(2) yields excellent agreement. PMID- 22080676 TI - Lessons from genetically altered mesenchymal stem cells (MSCs): candidates for improved MSC-directed myocardial repair. AB - The regenerative and reparative potential of mesenchymal stem cells (MSCs) make them attractive candidates for numerous cell-directed therapies. The variant degree of tissue repair by transplanted MSCs has been assessed in several published reports. There are many gaps in the knowledge of MSC biology and the underlying reasons for their disparate effectiveness in tissue repair. This review examines successful preclinical models of MSC-directed repair, particularly of myocardial repair, in an attempt to shed light into the events dictating MSC therapeutic efficacy. The reparative advantage of genetically altered MSCs will be described. This overview will elucidate possible molecular mechanisms that can influence MSC engraftment, differentiation, self-renewal, and ultimately increase wound repair. PMID- 22080677 TI - Acupuncture in the treatment of chronic pelvic pain secondary to pelvic inflammatory disease. PMID- 22080678 TI - Pediatric education programs. PMID- 22080679 TI - How should pediatricians in India address behavior patterns associated with childhood obesity? PMID- 22080680 TI - Recombinant macrophage targeted enzyme replacement therapy for Gaucher disease in India. AB - OBJECTIVE: Gaucher disease in India has been reported only in a few case reports from India. The aim of the study was to assess the response to enzyme replacement therapy in Indian patients with Gaucher disease. DESIGN: Retrospective analysis of patients receiving CHO-derived recombinant macrophage-targetted glucocorebrosidase. SETTING: Five centers from India with experience in treating lysosomal storage disorders. PATIENTS: The diagnosis of Gaucher disease was confirmed by low glucocerebrosidase levels, though it was first made on splenectomy in 8 and on bone marrow examination in 9 patients. Twenty five of 52 patients diagnosed with Gaucher disease (17 Type I, 8 mild Type III) received treatment for >6 months. Indications for treatment included symptomatic anemia, thrombo-cytopenia, organomegaly, bone disease or mild neurological symptoms leading to impairment of quality of life. Patients with significant neurological involvement were excluded. The drug infusions were given intravenously every 15 days. MAIN OUTCOME MEASURES: Hemoglobin, platelet counts, liver and spleen volumes and growth parameters. RESULTS: 22 of the 25 children who survived were analyzed. After 6 months of treatment, the mean (range) increase in hemoglobin was 1.5 (-3.4 to 6.1) g/dL (P=0.01) and in platelet count was 32 x 10(9)/L (-98.5 x 109 to 145.5 x10(9))/L (P=0.02). The mean (range) increase in weight was 3 kg ( 5.6 to 10.5) (P=0.04) and in height was 7.1 cm (0 to 26.5) (P=0.0003). Liver size decreased by a mean (range) of 38.5% (- 5.5 to 86.7) (P=0.0003) and the spleen size by 34.8% (0 to 91.7) (P=0.004). All patients had improvement in bone pains and in 2 patients, neurological symptoms improved with others remaining static. CONCLUSIONS: This is the first reported cohort of patients in India reporting our experience with imiglucerase enzyme replacement therapy for treatment of Gaucher Disease in India. PMID- 22080681 TI - Gauchers disease presenting with portal hypertension. AB - Gauchers disease is a rare lysosomal storage disorder characterized by abnormal accumulation of lipid-laden macrophages in different organs. Though hepatosplenomegaly is commonly found, symptomatic presentation with portal hypertension is rare. We report a child with liver cirrhosis and bleeding esophageal varices who was diagnosed with Gaucher's disease. PMID- 22080682 TI - Alveolar capillary dysplasia with anorectal anomaly. AB - Alveolar capillary dysplasia (ACD) is an uncommon cause of irreversible persistent pulmonary hypertension in full-term newborn. In ACD there is a failure of formation of air - blood barrier in addition to misalignment of pulmonary veins. The etiology of the disease is still not understood. We present a case report of a full-term newborn with ACD associated with anorectal anomaly. PMID- 22080683 TI - Lipoprotein lipase deficiency in an infant. AB - Patients with isolated hypertriglyceridemia usually present with recurrent abdominal pain, pancreatitis, eruptive xanthomas, lipemia retinalis and hepatosplenomegaly. We describe the diagnosis and treatment of an infant with severe hypertriglyceridemia. The child was found to be heterozygous for two novel mutations in the lipoprotein lipase gene. PMID- 22080684 TI - Transfusion related acute lung injury with intravenous immunoglobulin. AB - This case report describes transfusion related acute lung injury with the use of intravenous immunoglobulin in a child with Guillain barre syndrome. PMID- 22080685 TI - Kawasaki disease in association with urinary tract infection. AB - We report a 2-month-old infant with E. coli urinary tract infection, who did not respond to antibiotic therapy. She later developed clinical features fulfilling criteria of Kawasaki disease (KD), and was treated with intravenous immunolglobulin and aspirin. KD should be considered in the differential diagnosis in patients who present with infection and do not respond to antibiotic therapy. PMID- 22080686 TI - Prescribing practices of doctors in management of acute diarrhea. AB - We conducted this study to determine the prescribing practices of doctors in management of acute diarrhea in children in the age group of 6 month -5 year. Antimotility agents and low/zero lactose formula was prescibed in 9.8% and 24.7% cases, respectively by general practitioners. In about 66.6% and 5.7% cases pre/probiotics were prescribed and oral rehydration salt (ORS) were not prescribed by the pediatricians. PMID- 22080687 TI - Trend of antibiotic resistance in children with first acute pyelonephritis. AB - There have been many recent reports of increasing antimicrobial resistance among uropathogens. In this study, we reviewed medical records of children (<18 yr age) with first acute pyelonephritis admitted to our Institution between January 2005 to December 2009. 411 children (189 girls) were studied and increasing trend in bacterial resistance toward co-trimoxazole, 2nd and 3rd generation cephalosporins and gentamicin were observed. PMID- 22080688 TI - Trends of childhood vasculitides in eastern India. AB - A prospective follow up for 7 years (2004-2010) revealed 10.2% children (n=158) had vasculitis among all rheumatological cases (n=1544). Henoch-Schonlein Purpura (HSP) (56.9%) and Kawasaki disease (KD) (24%) were major groups. PMID- 22080689 TI - Adiponectin and pro-inflammatory cytokines in obese diabetic boys. AB - Adiponectin serum levels were significantly lower in obese diabetic than in non obese healthy boys (P <0.001). Circulating soluble E-selectin levels was significantly higher in obese diabetic boys than the healthy non-obese (P <0.01). There were significant inverse correlations between adiponectin and sE-selectin, hsCRP, IL-1b, and MCP-1 and positively with NOx. We conclude that sE-selectin and MCP-1 may represent a link between obesity and related co-morbidities in children and adults. PMID- 22080690 TI - Gram stain as a predictor of urinary infections in children under 2 years. PMID- 22080691 TI - Fate of award winning papers at annual conference of Indian Academy of Pediatrics: a 13 years experience. AB - The present study was conducted to determine the rate of publication of research papers winning awards at the annual pediatric conference of Indian Academy of Pediatrics. Secondary objective was to identify the factors facilitating their publication, if any. Overall, 75 papers were awarded between 1995 and 2007; of these, 28 (37%) were subsequently published till January 2011. Papers originating from North India, medical colleges, and those with an experimental design had higher chances of subsequent publication. PMID- 22080692 TI - Childhood acute lymphoblastic leukemia: need of a national population based registry. PMID- 22080693 TI - Pediatric BLS updates 2010. PMID- 22080694 TI - Efficacy and safety of azithromycin for typhoid fever. PMID- 22080695 TI - Hyperglycemia in the PICU: tread with caution. PMID- 22080696 TI - Pachyonychia congenita affecting only nails. PMID- 22080697 TI - HIV management returning to primary care providers. PMID- 22080698 TI - Improving drug labeling and counseling for limited English proficient adults. AB - Language barriers between patients and providers adversely affect quality of care and a patient's ability to obtain, understand, and act on health information. Health care organizations are mandated by law to provide language concordant services. While health systems have taken steps to promote language access, minimal effort has been made to improve pharmacy practice. This is problematic, as patient misunderstanding of prescription drug instructions is a root cause of many adverse drug events occurring annually in outpatient settings. Enhanced, language concordant prescription labeling and counseling is needed to promote safe use of prescription medications among limited English proficient patients. PMID- 22080699 TI - Improving patient provider communication for Latinos at Temple University Hospital and Temple University School of Medicine. AB - This Report from the Field documents a series of interventions developed by Temple University Health System and School of Medicine through participation in the RWJF initiative entitled Hablamos Juntos. The report delineates outcomes to date demonstrating that these interventions have met the challenge of improving patient provider communication for Latinos. PMID- 22080700 TI - Medical home disparities for Latino children by parental language of interview. AB - Examination of Latino children in aggregate ignores important subgroup differences due to the parents' English language ability. Previous reports of the pediatric medical home have not stratified Latino children by parental language differences to compare the two groups directly. We analyzed the 2007 National Survey of Children's Health to determine medical home prevalence among Latino children, stratified by language of parental interview. Most Latino children with a Spanish-language parental interview had a usual source of care, but only one quarter had a medical home. Striking medical home disparities persisted for Latino children with a Spanish-language interview, even after adjustment for potential confounders. Lack of a medical home was associated with disparities in the quality of care, more so than access disparities. Addressing health care disparities for Latino children requires particular attention to the unique needs of Latino children with parents who may experience language barriers during health care encounters. PMID- 22080701 TI - Quality of reproductive health services to limited English proficient (LEP) patients. AB - BACKGROUND: Medical patients with limited English proficiency (LEP) frequently receive health care services of suboptimal quality. METHODS: We explored whether clients served with staff interpreters (language-discordant, LDI) receive reproductive health care of lower quality than clients seen by a bilingual clinician (language concordant, LC). We conducted a medical record review of 1,589 reproductive health visits of female and male LEP clients. RESULTS: Multivariate analyses showed that LDI visits were significantly less likely than LC visits to contain documentation of the provision of education and counseling services and less likely to have documentation of sexually transmitted infection (STI) risk assessment among new female clients. Female clients in LDI and LC visits were equally likely to be tested for Chlamydia. CONCLUSIONS: Quality improvement activities should target family planning providers who must use interpreters when serving LEP clients. Medical charts should document the use of interpreters and bilingual clinicians to monitor quality of care. PMID- 22080702 TI - Health Professional Shortage Areas, insurance status, and cardiovascular disease prevention in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. AB - Individuals with cardiovascular disease (CVD) living in Health Professional Shortage Areas (HPSA) may receive less preventive care than others. The Reasons for Geographic And Racial Differences in Stroke Study (REGARDS) surveyed 30,239 African American (AA) and White individuals older than 45 years of age between 2003-2007. We compared medication use for CVD prevention by HPSA and insurance status, adjusting for sociodemographic factors, health behaviors, and health status. Individuals residing in partial HPSA counties were excluded. Mean age was 64+/-9 years, 42% were AA, 55% were women, and 93% had health insurance; 2,545 resided in 340 complete HPSA counties and 17,427 in 1,145 non-HPSA counties. Aspirin, beta-blocker, and ACE-inhibitor use were similar by HPSA and insurance status. Compared with insured individuals living in non-HPSA counties, statin use was lower among uninsured participants living in non-HPSA and HPSA counties. Less medication use for CVD prevention was not associated with HPSA status, but less statin use was associated with lack of insurance. PMID- 22080703 TI - Predictors of body mass index among low-income community-dwelling older adults. AB - This study investigated demographic, behavioral, and functional predictors of overweight and obesity, using secondary data from 705 community-dwelling individuals aged 65 years and older receiving or seeking Medicaid personal care services. Half of the participants were obese, while an additional 28% were overweight. The relationships between body mass index (BMI) levels and selected independent variables were analyzed. Females were more likely to be obese, while those who were older (75 years or older), more cognitively impaired, and smoked were less likely to obese. Comparing obesity with being overweight, being female and reporting more pain symptoms increased the odds of being obese, whereas being older (75 years or older) and being more cognitively impaired decreased the odds. The especially high rates of obesity in Texas have a profound impact on personal health and may result in increased health care costs that threaten public programs as well. PMID- 22080704 TI - A multilevel assessment of barriers to adoption of Dietary Approaches to Stop Hypertension (DASH) among African Americans of low socioeconomic status. AB - BACKGROUND: We examined perceptions of Dietary Approaches to Stop Hypertension (DASH) and the food environment among African Americans (AA) with high blood pressure living in two low-income communities and objectively assessed local food outlets. METHODS: Focus groups were conducted with 30 AAs; participants discussed DASH and the availability of healthy foods in their community. Sessions were transcribed and themes identified. Fifty-four stores and 114 restaurants were assessed using the Nutrition Environment Measures Survey (NEMS). RESULTS: Common themes included poor availability, quality, and cost of healthy foods; tension between following DASH and feeding other family members; and lack of congruity between their preferred foods and DASH. Food outlets in majority AA census tracts had lower NEMS scores (stores: -11.7, p=.01, restaurants: -8.3, p=.001) compared with majority White areas. CONCLUSIONS: Interventions promoting DASH among lower income AAs should reflect the food customs, economic concerns, and food available in communities. PMID- 22080705 TI - Adults with diagnosed and untreated diabetes: who are they? How can we reach them? AB - Untreated or undertreated diabetes can cause debilitating complications such as blindness and amputations. Information about the factors associated with diagnosed but untreated diabetes may help target efforts to promote appropriate treatment. Using the Medical Expenditure Panel Survey, we examine: (1) use of insulin or oral medications, (2) use of diet only, and (3) no treatment. We analyze covariates of this trichotomous outcome using multinomial logit regression. Among adults diagnosed with diabetes, 87.0% used oral medications or insulin, 10.6% used diet only, and 2.4% were untreated. Lacking a usual source of care, poor mental health, being single, and being an Asian/Pacific Islander are associated with lack of treatment. Better health, lacking a usual source of care, and attitudes against medical care are associated with using diet only. Adults with diagnosed but untreated or undertreated diabetes may be difficult for service providers to reach, and multiple strategies are needed to initiate treatment. PMID- 22080706 TI - Diabetes and psychological profile of younger rural African American women with type 2 diabetes. AB - PURPOSE: To describe diabetes self-care behaviors, diabetes-related distress, depressive symptoms, and diabetes-related needs among rural African American women with type 2 diabetes ages 21-50. METHODS: A cross-sectional survey, including questionnaires and a single, open-ended question, was used to assess constructs of interest. FINDINGS: Taking medication was the most frequently reported (5.5 days/week) self-care activity and exercise the least (3.0 days/week). Nearly half (44%) reported worrying about diabetes complications. Approximately one-third (31%) felt guilty about inconsistent self-care or fearful about living with diabetes. Seventy percent had a depression score suggestive of significant depressive symptomatology. Most diabetes-related concerns were about diet (34%) (i.e., what to eat), exercise (30%), taking medications (10%), and finances (8%). CONCLUSIONS: Future research should explore specific diabetes self care barriers/enablers and interventions should provide women with diabetes education, barrier management, and psychological support. Innovative delivery strategies are needed to provide this support in resource-limited rural communities. PMID- 22080707 TI - Utility of a point-of-care device in recruiting ethnic minorities for diabetes research with community partners. AB - BACKGROUND: Recruitment of hard-to-reach ethnic minorities such as Korean Americans (KAs) requires substantial time, cost, and strategic effort. A point-of care (POC) A1c test could facilitate the recruitment of such populations for diabetes research in community settings. METHODS: A two-step approach for participant screening was employed: Potential participants were first screened using the POC A1c test at a community location. Only those with POC A1c levels >=7.5% were referred for a confirmatory lab test within two weeks. RESULTS: In total, 237 KAs were screened using the POC A1c test; 92 were referred for confirmatory testing and 83 who got the laboratory A1c measurement were confirmed eligible (A1c >=7.5%). There was a strong positive correlation between the POC and reference laboratory measurements (rho=0.83, p<=.001). CONCLUSION: Using a POC A1c method as a front-line screening test can facilitate the recruitment of KAs with type 2 diabetes, while saving cost, time, and effort. PMID- 22080708 TI - Self-reported asthma among American Indian and Alaska Native people in Alaska. AB - This study describes the lifetime prevalence of self-reported asthma among American Indian and Alaska Native (AI/AN) people who participated in the Education and Research Towards Health (EARTH) study in Alaska. We conducted a cross-sectional analysis of asthma prevalence by sex and its associations with sociodemographic, health, and environmental factors. Among 3,828 AI/AN adults, we found a higher age-sex adjusted prevalence of asthma (15.4%) than is found in the general U.S. adult (11.0%) population based on the 2006 National Health Interview Survey. After multivariable analysis, self-reported asthma among men was associated with increased age, unemployment, lower income, and obesity. Among women, self-reported asthma was associated with increased age, being divorced/separated, living in Alaska's southcentral region, self-reported fair/poor health status, obesity, and indoor mold. Our data suggest that AI/AN adults have higher prevalence of lifetime asthma than the general U.S. population. Further study is necessary to understand asthma in this population. PMID- 22080709 TI - The association between housing instability, food insecurity, and diabetes self efficacy in low-income adults. AB - Limited data exist on whether structural factors associated with poverty such as inadequate housing and food insecurity affect diabetes care. In a sample of low income participants with diabetes (N=711), we sought to determine if housing instability was associated with lower diabetes self-efficacy, and whether this relationship was mediated by food insecurity. We ordered housing from most to least stable. We observed a linear decrease in diabetes self-efficacy as housing instability increased (p<.01). After adjusting for age, sex, race/ethnicity, and alcohol or substance use, adults lacking a usual place to stay had lower self efficacy than those who owned their own home (beta-coefficient -0.94, 95% CI 1.88, -0.01). Food insecurity mediated the association between housing instability and diabetes self-efficacy (beta-coefficient -0.64, 95% CI -1.57, 0.31). Our findings suggest that inadequate access to food lowers self-efficacy among adults with diabetes, and supports provision of food to unstably housed adults as part of diabetes care. PMID- 22080710 TI - Addressing depression and accumulated trauma in urban primary care: challenges and opportunities. AB - This paper explores the presentation of severe depression among patients with accumulated trauma in the context of an urban community health center (primary care clinic) in California, as well as opportunities to address this phenomenon in light of diminished community-based mental health services. PMID- 22080711 TI - Specialty care referral patterns for the underserved: a study of community health centers on the South Side of Chicago. AB - Little is known about the primary-specialty care interface for underserved patients. In order better to understand inter-physician communication patterns in urban community health centers (CHCs), we conducted a retrospective chart review of specialty care referrals for patients from four South Side Chicago CHCs. Of the 406 identified referrals, 74% (n=301) were made from CHCs that employed referral coordinators and 64% (n=258) were made to affiliated specialists. Chart documentation of whether or not the patient attended the referred specialty visit was present for 43% (n=176) of referrals, and communication from the specialist to the referring clinician was present for 31% (n=127) of referrals. Employing CHC referral coordinators was positively associated with documented specialty clinical communication (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1 3.2). Use of referral coordinators to facilitate care and integrating delivery systems to increase information sharing appear to improve care coordination, but further investigation is warranted. PMID- 22080712 TI - Stress and the social determinants of maternal health among Puerto Rican women: a CBPR approach. AB - This qualitative research project explores how poverty, the built environment, education, working conditions, health care access, food insecurity and perceived discrimination are experienced by Puerto Rican Latinas through the course of their lives. Five focus groups were conducted with the primary objective of documenting community experiences and perspectives regarding: 1) stress, including perceived discrimination based on race/ethnicity (racism); 2) the impact of stress on Puerto Rican women of reproductive age, their families, and/or their community; and 3) stressors that affect maternal health. Focus groups were conducted in English and Spanish in the two cities with the highest rates of premature birth and low infant birthweight in the state of Connecticut. Focus group findings indicate that participants perceived poverty, food insecurity, lack of access to quality education, and unsafe environments as significant life stressors affecting maternal and child health. PMID- 22080713 TI - A pre-post survey analysis of satisfaction with health care and medical mistrust after patient navigation for American Indian cancer patients. AB - PURPOSE: To assess the impact of patient navigation (PN) on satisfaction with health care and medical mistrust among American Indians (AI) undergoing cancer treatment. METHODS: This was a pre-post cohort survey study of 52 AI cancer patients who participated in a culturally-tailored PN program during their cancer treatment. Surveys were administered prior to and after cancer treatment assessing medical mistrust and satisfaction with health care using two Likert type scales. RESULTS: Participation refusal rate was 7%. Mean scale scores for satisfaction with health care were significantly improved after PN compared with pre-navigation (p<.0001; Wilcoxon signed-rank test). There was no significant difference in the mean scale scores for medical mistrust after PN compared with those observed prior to treatment (p=.13). CONCLUSIONS: American Indian cancer patients who received PN services during their cancer treatment showed improvement in levels of satisfaction with health. However, no improvements were observed in levels of medical mistrust. PMID- 22080714 TI - Psychosocial risk screening during pregnancy: additional risks identified during a second interview. AB - The Prenatal Risk Overview (PRO) screens for 13 psychosocial risk factors associated with poor birth outcomes. This study assessed the extent to which risk factors unreported during an intake interview were identified during a subsequent interview. A total of 708 pregnant women were screened and re-screened at three urban community health care centers between July 2007 and April 2010. Study participants were predominantly young (mean age 23.5 years), unmarried (75.1%) women of color (92.5%); 38.4% were foreign-born. The proportional increase in participants identified as being at risk for individual domains at the second interview ranged from 5.6% to 49.0% for the combined Moderate/High Risk classification and from 5.6% to 73.0% for the High Risk only classification. For women whose health and well-being are challenged by poverty, violence, social isolation, and other stressors, both initial screening and repeat screening offer opportunities to alleviate identified risks. PMID- 22080715 TI - Expert communication training for providers in community health centers. AB - BACKGROUND: Community health center (CHC) clinicians describe significant challenges in delivering care for populations with complex health needs. INTERVENTION: A three-workshop series was presented to 102 providers working in CHCs. Training focused on four areas identified through online needs assessment: challenging interactions; patient perspective; health literacy; and motivational interviewing. EVALUATION METHODS: A retrospective pre-post evaluation measured self-perceived change in content knowledge in all four areas. Participants documented commitments to change behaviors across workshops, which were analyzed for recurring themes. RESULTS: Paired t-tests documented improvement in all four content areas. Content analysis of commitments yielded four themes: empowering patients, structuring care, understanding patients, and reflecting purposefully. Of the sixty-eight percent of participants responding to post-workshop queries about their commitments (n=70), 94% report having fully implemented changes in practice behavior or planning to do so. CONCLUSIONS: Providers at CHCs benefit from opportunities to learn and reflect together about communication challenges in practice. PMID- 22080716 TI - Patients' reports about medical doctors' inquiries on their mental health: do generational status, ethnicity and mental health/substance use disorders matter? AB - Immigrants are less likely than others to use mental health (MH) services. Physicians' limited time often precludes inquiry about MH. This study investigated the influence of generational status, ethnicity, and mental/substance use disorders on physicians' inquiries about Asian American (AA) MH. Data from the National Latino and Asian American Study were analyzed (n=1,853). The outcome was past year physician's inquiry regarding MH. Results revealed that AA with U.S.-born parents had significantly greater odds compared to AA born outside the U.S. to report that their doctors inquired about their MH (OR=218, 95% CI: 1.28, 3.73). Past year mental/substance use disorder increased the odds of AA reporting that their doctors inquired about their MH (OR=8.41; 95% CI: 3.28, 21.66). This increase differed by ethnicity, with Chinese less affected than Vietnamese (OR=0.17; 95% CI: 0.05, 0.59). The reasons for these associations warrant further exploration. PMID- 22080717 TI - Perceptions of coercion, discrimination and other negative experiences in postpartum contraceptive counseling for low-income minority women. AB - BACKGROUND: Using in-depth qualitative methods, we investigated negative contraception counseling experiences, including those felt to be coercive or discriminatory, in a population of postpartum urban minority women. METHODS: Brief surveys and semi-structured interviews were conducted with 30 consenting postpartum women who had received care at a Medicaid-funded obstetrics clinic. In person one-on-one interviews were then reviewed for themes using an iterative process of qualitative analysis. RESULTS: In this sample of African American (63%) and Hispanic (37%) women (median age 26), 73% had unplanned pregnancies. Features of negative counseling experiences included having insufficient, non physician-directed and impersonal counseling. Most women had experienced episodes of poor communication with providers; 10 described feeling coerced or perceiving racially-based discrimination in counseling. CONCLUSIONS: Negative experiences with contraceptive counseling may affect contraception utilization. Contraceptive education should respect each individual's autonomy, culture, and values. PMID- 22080718 TI - Closing the implementation gap in services for children affected by HIV/AIDS: from assisting orphans and vulnerable children (OVC) to providing long-term opportunities for economic growth. AB - While delivering innovative care for over 17 million children living with and affected by HIV/AIDS is a priority for today's global health community, most of these children's health needs remain unmet. Concerns about funding, implementation, and transparency continue to obstruct quality care for all. This paper discusses why services supported by macro-level funding, local initiatives, innovative financing, and enhanced long-term development strategies, are imperative. Concurrent advocacy and preventive measures, such as universal access to education, can sustain this investment in human capital. Such efforts may enhance economic growth, expand local capacity, and improve the quality of life in communities currently burdened by the HIV epidemic. PMID- 22080719 TI - Fee-for-service and managed care for seniors and people with disabilities on Medicaid: implications for the managed care mandate in California. AB - OBJECTIVE: To assess differences in perceived quality of care between fee-for service (FFS) and managed care Medicaid (MMC) by seniors and persons with disabilities (SPD) and to generate hypotheses for future evaluations of the new managed care mandate for SPD in California. METHODS: A cross-sectional telephone survey of 403 SPD Medicaid beneficiaries comparing perceived access to, satisfaction with, and quality of care between beneficiaries who had voluntarily enrolled in MMC with those who had remained in FFS. RESULTS: Beneficiaries in MMC were more likely to be "very satisfied" with their benefits than those in FFS. There was no significant difference on any measure of access to care. Most beneficiaries in MMC reported their access to and quality of health care was either the same or better than it had been in FFS. CONCLUSION: On most measures, MMC was rated either the same or better than FFS by SPD beneficiaries who voluntarily enrolled in MMC. PMID- 22080720 TI - The effect of class size in grades K-3 on adult earnings, employment, and disability status: evidence from a multi-center randomized controlled trial. AB - BACKGROUND: Early education interventions have been forwarded as a means for reducing social disparities in income and health in adulthood. We explore whether a successful early education intervention, which occurred between 1985 and 1989, improved the employment rates, earnings and health of blacks relative to whites through 2008. METHODS: We used data from Project STAR (Student Teacher Achievement Ratio), a four-year multi-center randomized controlled trial of reduced class sizes in Tennessee involving 11,601 students. Students were initially randomized within 79 schools to classes with 22-25 or 13-17 students. We linked subject records to Social Security Administration (SSA) earnings and disability data collected between 1997 and 2008-when the majority of subjects were between the ages of 18 and 28. We focused our analysis on annual, rather than cumulative, measures of earnings and employment because educational attainment after high school might reduce earnings through age 23. We considered three or more years of statistically significant positive (or negative) annual impacts to be a meaningful effect. RESULTS: Project STAR improved cognition and high school graduation rates. These benefits were primarily realized among low income and minority students. These early education benefits did not translate into reduced disability claims in adulthood for treated subjects. However, exposure to small class size increased employment for blacks, and increased earnings for black males (p<0.05). Exposure to small classes also led to an increase in earnings for white males. However, white females exposed to small classes experienced a net decline in earnings and employment across the later years of follow up (p<0.05), offsetting any gains by white males. CONCLUSIONS: Exposure to small class size in grades K-3 appears to improve earnings and employment for black males and earnings for white males, while reducing employment and earnings among white females. PMID- 22080722 TI - Pressure-induced phase transition(s) in KMnF3 and the importance of the excess volume for phase transitions in perovskite structures. AB - We report a pressure-dependent investigation of KMnF(3) by x-ray diffraction up to 30 GPa. The results are discussed in the framework of Landau theory and in relation to the isostructural phase transition in SrTiO(3). The phase transition temperature near 186 K in KMnF(3) shifts to room temperature at a critical pressure of P(c) = 3.4 GPa; the pressure dependence of the transition point follows DeltaP(c)/DeltaT(c) = 0.0315 GPa K(-1). The transition becomes second order under high pressure, close to the tricritical point. The phase transition is determined by the rotation of MnF(6) octahedra with their simultaneous expansion along the rotation axis. The rotation angle was found to increase to 10.5 degrees at 24 GPa. An additional anomaly was observed at higher pressure around 25 GPa, suggesting a further phase transition. PMID- 22080723 TI - "Every case of asphyxia can be used as a learning example". Conclusions from an analysis of substandard obstetrical care. AB - AIM: To propose suggestions for improvements in care based on conclusions from studies on low Apgar scores and substandard care during labor. SETTING AND PATIENTS: Studies on infants with low Apgar scores in a general obstetric population 2004-2006 and claims for financial compensation on the behalf of infants, based on the suspicion that substandard care in conjunction with childbirth has caused severe asphyxia or neonatal death in Sweden 1990-2005. RESULTS: The most common flaws were related to insufficient fetal surveillance, defective interpretation of cardiotocography (CTG) tracings, not acting in a timely fashion on abnormal CTG, and the incautious use of oxytocin. Besides, in half of the infants a suboptimal mode of delivery added further trauma to the already asphyxiated infant. Additionally, resuscitation was unsatisfactory in many of these infants. The most critical flaw was defective compliance with the guidelines concerning ventilation and the early paging of skilled personnel in cases of imminent asphyxia or known complications during labor. In many case reports, the documentation of the neonatal resuscitation was insufficient to enable accurate and reliable evaluation. CONCLUSIONS: Examples of proposed improvements in care during labor are the introduction of a permanent educational atmosphere with aside time for daily educational rounds and discussion, cooperation around the use of standardized terminology in CTG interpretation, the cautious use of oxytocin, and the routine paging of a pediatrician before birth in cases of complicated delivery or imminent asphyxia. The proposed interventions need to be evaluated in clinical trials in the future. PMID- 22080724 TI - Nonprescription steroids on the Internet. AB - This study evaluated the degree to which anabolic-androgenic steroids are proffered for sale over the Internet and how they are characterized on popular Web sites. Searches for specific steroid product labels (e.g., Dianabol) between March 2006 and June 2006 revealed that approximately half of the Web sites advocated their "safe" use, and roughly one third offered to sell them without prescriptions. The Web sites frequently presented misinformation about steroids and minimized their dangers. Less than 5% of the Web sites presented accurate health risk information about steroids or provided information to abusers seeking to discontinue their steroid use. Implications for education, prevention, treatment, and policy are discussed. PMID- 22080725 TI - Subtypes of alcohol dependence and their effect on sexual behavior change. AB - This study utilized data from a National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism funded community-based HIV prevention program in the Midwest in 2000. We categorized women who met lifetime criteria for alcohol dependence (using the DIS) and who also had used cocaine (n = 324) into four alcohol typologies based on onset of regular drinking and the length of time to dependence. The Risk Behavior Assessment measured sex behaviors, combined into a risk index, before and after the program. Generalized linear modeling compared decreases over time. Women who began drinking regularly later and became dependent more slowly significantly decreased risky sex behaviors. Tailored prevention protocols may more effectively decrease HIV risk. PMID- 22080726 TI - Forster resonance energy transfer-based biosensors for multiparameter ratiometric imaging of Ca2+ dynamics and caspase-3 activity in single cells. AB - As one of the principal cytoplasmic second messengers, the calcium ion (Ca(2+)) is central to a variety of intracellular signal transduction pathways. Accordingly, there is a sustained interest in methods for spatially- and temporally resolved imaging of the concentration of Ca(2+) in live cells using noninvasive methods such as genetically encoded biosensors based on Forster resonance energy transfer (FRET) between fluorescent proteins (FPs). In recent years, protein-engineering efforts have provided the research community with FRET based Ca(2+) biosensors that are dramatically improved in terms of enhanced emission ratio change and optimized Ca(2+) affinity for various applications. We now report the development and systematic optimization of a pair of spectrally distinct FRET-based biosensors that enable the simultaneous imaging of Ca(2+) in two compartments of a single cell without substantial spectral crosstalk between emission channels. Furthermore, we demonstrate that these new biosensors can be used in conjunction with previously reported caspase-3 substrates based on the same set of FRET pairs. PMID- 22080727 TI - Electronic structure, optical properties and lattice dynamics of MgSO3.6H2O. AB - The electronic band structure, optical properties and lattice vibrations of MgSO(3).6H(2)O were studied within density functional theory and compared to the experimental optical data and polarized Raman spectra. Due to the 'molecular' nature of the MgSO(3).6H(2)O crystal all Gamma-point phonon modes could be separated into groups belonging to specific structural blocks: Mg(H(2)O)(6) octahedra, SO(3) units and H(2)O molecules. All Raman lines in the experimental spectra are assigned to definite vibrations of the structure and reasonable agreement is found between theoretical and experimental mode frequencies. The temperature-dependent Raman spectra reveal at 60 degrees C a sharp transition from MgSO(3).6H(2)O to anhydrous amorphous MgSO(3) without the noticeable presence of intermediate lower hydrates, such as MgSO(3).3H(2)O. PMID- 22080728 TI - Hydroxylamine reduction to ammonium by plant and cyanobacterial hemoglobins. AB - Plants often face hypoxic stress as a result of flooding and waterlogged soils. During these periods, they must continue ATP production and nitrogen metabolism if they are to survive. The normal pathway of reductive nitrogen assimilation in non-legumes, nitrate, and nitrite reductase can be inhibited during low oxygen conditions that are associated with the buildup of toxic metabolites such as nitrite and nitric oxide, so the plant must also have a means of detoxifying these molecules. Compared to animal hemoglobins, plant and cyanobacterial hemoglobins are adept at reducing nitrite to nitric oxide under anaerobic conditions. Here we test their abilities to reduce hydroxylamine, a proposed intermediate of nitrite reductase, under anaerobic conditions. We find that class 1 rice nonsymbiotic hemoglobin (rice nsHb1) and the hemoglobin from the cyanobacterium Synechocystis (SynHb) catalyze the reduction of hydroxylamine to ammonium at rates 100-2500 times faster than animal hemoglobins including myoglobin, neuroglobin, cytoglobin, and blood cell hemoglobin. These results support the hypothesis that plant and cyanobacterial hemoglobins contribute to anaerobic nitrogen metabolism in support of anaerobic respiration and survival during hypoxia. PMID- 22080729 TI - Clock gene expression levels and relationship with clinical and pathological features in colorectal cancer patients. AB - The clock gene machinery controls cellular metabolism, proliferation, and key functions, such as DNA damage recognition and repair. Dysfunction of the circadian clock is involved in tumorigenesis, and altered expression of some clock genes has been found in cancer patients. The aim of this study was to evaluate the expression levels of core clock genes in colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (qPCR) was used to examine ARNTL1, CLOCK, PER1, PER2, PER3, CRY1, CRY2, Timeless (TIM), TIPIN, and CSNK1? expression levels in the tumor tissue and matched apparently healthy mucosa of CRC patients. In the tumor tissue of CRC patients, compared to their matched healthy mucosa, expression levels of ARNTL1 (p=.002), PER1 (p=.002), PER2 (p=.011), PER3 (p=.003), and CRY2 (p=.012) were lower, whereas the expression level of TIM (p=.044) was higher. No significant difference was observed in the expression levels of CLOCK (p=.778), CRY1 (p=.600), CSNK1 (p=.903), and TIPIN (p=.136). As to the clinical and pathological features, a significant association was found between low CRY1 expression levels in tumor mucosa and age (p=.026), and female sex (p=.005), whereas high CRY1 expression levels in tumor mucosa were associated with cancer location in the distal colon (p?=?.015). Moreover, high TIM mRNA levels in the tumor mucosa were prevalent whenever proximal lymph nodes were involved (p= .013) and associated with TNM stages III-IV (p=.005) and microsatellite instability (p=.015). Significantly poorer survival rates were evidenced for CRC patients with lower expression in the tumor tissue of PER1 (p=.010), PER3 (p= .010), and CSNKIE (p=.024). In conclusion, abnormal expression levels of core clock genes in CRC tissue may be related to the process of tumorigenesis and exert an influence on host/tumor interactions. PMID- 22080730 TI - Epigenetic impact of long-term shiftwork: pilot evidence from circadian genes and whole-genome methylation analysis. AB - Epigenetic association studies have demonstrated differential promoter methylation in the core circadian genes in breast cancer cases relative to cancer free controls. The current pilot study aims to investigate whether epigenetic changes affecting breast cancer risk could be caused by circadian disruption through exposure to light at night. Archived DNA samples extracted from whole blood of 117 female subjects from a prospective cohort conducted in Denmark were included in this study. A polymerase chain reaction (PCR)-based method was used for detection of gene-promoter methylation, whereas genome-wide methylation analysis was performed using the Illumina Infinium Methylation Chip. Long-term shiftwork resulted in the same promoter hypomethylation of CLOCK and hypermethylation of CRY2, as was previously observed in breast cancer case control studies. Genome-wide methylation analysis further discovered widespread methylation alterations in shiftworkers, including changes in many methylation- and cancer-relevant genes. Pathway analysis of the genes with altered methylation patterns revealed several cancer-related pathways. One of the top three networks generated was designated as "DNA replication, recombination, and repair, gene expression, behavior" with ESR1 (estrogen receptor alpha) featured most prominently in the network, underscoring the potential breast cancer relevance of the genes differentially methylated in long-term shiftworkers. These results, although exploratory, demonstrate the first evidence of the cancer-relevant epigenetic effects of night shiftwork, which warrant further investigation. Considering there are millions of shiftworkers worldwide, understanding the effects of this exposure may lead to novel strategies for cancer prevention and new policies regulating shiftwork. PMID- 22080731 TI - Timekeeping through social contacts: social synchronization of circadian locomotor activity rhythm in the carpenter ant Camponotus paria. AB - In ant colonies a large proportion of individuals remain inside nests for most of their lives and come out only when necessary. It is not clear how, in a nest of several thousand individuals, information about local time is communicated among members of the colony. Central to this seem to be circadian clocks, which have an intrinsic ability to keep track of local time by entraining to environmental light-dark, temperature, and social cycles. Here, the authors report the results of their study aimed at understanding the role of cyclic social interactions in circadian timekeeping of a day-active species of carpenter ant Camponotus paria. The authors found that daily social interactions with visitors (worker ants) was able to synchronize the circadian locomotor activity rhythm of host worker ants and queens, in one-on-one (pair-wise) and multi-individual (group-wise) interactions. Interestingly, the outcome of cyclic social interactions was context specific; when visitor workers socially interacted with host workers one on-one, host workers considered the time of interaction as subjective day, but when visitor workers interacted with a group of workers and queens, the hosts considered the time of interaction as subjective night. These results can be taken to suggest that members of the ant species C. paria keep track of local time by socially interacting with workers (foragers) who shuttle in and out of the colony in search of food. (Author correspondence: vsharma@jncasr.ac.in ). PMID- 22080732 TI - The daily melatonin pattern in Djungarian hamsters depends on the circadian phenotype. AB - Djungarian hamsters (Phodopus sungorus) bred at the Institute of Halle reveal three different circadian phenotypes. The wild type (WT) shows normal locomotor activity patterns, whereas in hamsters of the DAO (delayed activity onset) type, the activity onset is continuously delayed. Since the activity offset in those hamsters remains coupled to "light-on," the activity time becomes compressed. Hamsters of the AR (arrhythmic) type are episodically active throughout the 24 h. Previous studies showed that a disturbed interaction of the circadian system with the light-dark (LD) cycle contributes to the phenomenon observed in DAO hamsters. To gain better insight into the underlying mechanisms, the authors investigated the daily melatonin rhythm, as it is a reliable marker of the circadian clock. Hamsters were kept individually under standardized laboratory conditions (LD 14:10, T=22 degrees C+/-2 degrees C, food and water ad libitum). WT, DAO (with exactly 5 h delay of activity onset), and AR hamsters were used for pineal melatonin and urinary 6-sulfatoxymelatonin (aMT6s) measurement. Pineal melatonin content was determined at 3 time points: 4 h after "light-off" [D+4], 1 h before "light-on" [L-1], and 1h after "light-on" [L+1]). The 24-h profile of melatonin secretion was investigated by transferring the animals to metabolic cages for 27?h to collect urine at 3-h intervals for aMT6s analysis. WT hamsters showed high pineal melatonin content during the dark time (D+4, L-1), which significantly decreased at the beginning of the light period (L+1). In contrast, DAO hamsters displayed low melatonin levels during the part of the dark period when animals were still resting (D+4). At the end of the dark period (L-1), melatonin content increased significantly and declined again when light was switched on (L+1). AR hamsters showed low melatonin levels, comparable to daytime values, at all 3 time points. The results were confirmed by aMT6s data. WT hamsters showed a marked circadian pattern of aMT6s excretion. The concentration started to increase 3?h after "light-off" and reached daytime values 5 h after "light-on." In DAO hamsters, in contrast, aMT6s excretion started about 6?h later and reached significantly lower levels compared to WT hamsters. In AR animals, aMT6s excretion was low at all times. The results clearly indicate the rhythm of melatonin secretion in DAO hamsters is delayed in accord with their delayed activity onset, whereas AR hamsters display no melatonin rhythm at all. Since the regulatory pathways for the rhythms of locomotor activity and melatonin synthesis (which are downstream from the suprachiasmatic nucleus [SCN]) are different but obviously convey the same signal, we conclude that the origin of the phenomenon observed in DAO hamsters must be located upstream of the SCN, or in the SCN itself. PMID- 22080733 TI - Chronotype predicts activity patterns in the neural underpinnings of the motor system during the day. AB - Neuroimaging is increasingly used to study the motor system in vivo. Despite many reports of time-of-day influences on motor function at the behavioral level, little is known about these influences on neural motor networks and their activations recorded in neuroimaging. Using functional magnetic resonance imaging (fMRI), the authors studied 15 healthy subjects (9 females; mean +/- SD age: 23 +/- 3 yrs) performing a self-paced finger-tapping task at different times of day (morning, midday, afternoon, and evening). Blood-oxygenation-level-dependent signal showed systematic differences across the day in task-related motor areas of the brain, specifically in the supplementary motor area, parietal cortex, and rolandic operculum (p(corr)< .0125). The authors found that these time-of-day dependent hemodynamic modulations are associated with chronotype and not with homeostatic sleep pressure. These results show that consideration of time-of-day for the analysis of fMRI studies is imperative. PMID- 22080734 TI - Differential roles of breakfast and supper in rats of a daily three-meal schedule upon circadian regulation and physiology. AB - The timing of meals has been suggested to play an important role in circadian regulation and metabolic health. Three meals a day is a well-established human feeding habit, which in today's lifestyle may or may not be followed. The aim of this study was to test whether the absence of breakfast or supper significantly affects the circadian system and physiological function. The authors developed a rat model for their daily three meals study, whereby animals were divided into three groups (three meals, TM; no first meal, NF; no last meal, NL) all fed with the same amount of food every day. Rats in the NF group displayed significantly decreased levels of plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL C), and glucose in the activity phase, accompanied by delayed circadian phases of hepatic peripheral clock and downstream metabolic genes. Rats in the NL group showed lower concentration of plasma TC, HDL-C, and glucose in the rest phase, plus reduced adipose tissue accumulation and body weight gain. Real-time polymerase chain reaction (PCR) analysis indicated an attenuated rhythm in the food-entraining pathway, including down-regulated expression of the clock genes Per2, Bmal1, and Rev-erbalpha, which may further contribute to the delayed and decreased expression of FAS in lipogenesis in this group. Our findings are consistent with the conclusion that the daily first meal determines the circadian phasing of peripheral clocks, such as in the liver, whereas the daily last meal tightly couples to lipid metabolism and adipose tissue accumulation, which suggests differential physiological effects and function of the respective meal timings. PMID- 22080735 TI - Chronotype and the transition to college life. AB - Social synchronizers of morningness-eveningness, or chronotype, begin to change during the developmental transition from adolescence to college life. The current study examined how these changes related to the sleep/wake patterns of 220 undergraduates (93 males/122 females) ranging in age from 18 to 29 yrs at a private university. Coping strategies students used to deal with early morning commitments and familial conflict over sleep patterns were also examined. Results revealed that evening chronotypes were more likely to report conflict with parents in junior high school and high school over going to bed and waking, followed by a shift to a later sleep/wake pattern in college. They also reported adjusting their schedules and using more coping strategies to accommodate their evening bias. Morning chronotypes, whose routines easily fit a conventional morning schedule, reported little change in schedules and sleep patterns from junior high school to college, and used fewer coping strategies in response to early morning commitments. The shift in social zeitgebers from junior high school to college are significant, and yet little research has examined the effect these changes can have on students' adjustment to college life and the role that chronotype plays in this process. Because students' ability to cope with these changes will ultimately influence how successful they are in their various endeavors, a greater understanding of how chronotype is related to adaptive functioning across this developmental period is needed. PMID- 22080737 TI - The pattern of entrainment of the human sleep-wake rhythm by the natural photoperiod in the north. AB - Recently, it was shown that the sleep-wake rhythm of the inhabitants of the temperate zone is entrained to sun time. In the North, significant seasonal changes in the photoperiod may interfere with entrainment of the circadian system to sunlight. This investigation assessed the influence of photoperiod characteristics on the sleep length and sleep-wake rhythm of residents of high latitude. The study was conducted in four towns and six villages located between 59.5?N and 67.6?N latitude between the months of October and May from 2009 through 2011 and included 2822 subjects aged 10 to 97 yrs, 1621 of whom were females and 1201 males. The chronotype and sleep length of the subjects were assessed using the Munich Chronotype Questionnaire. The instructions for the questionnaire stressed the need to specify the sleep-wake schedule during the week preceding the date of completing the questionnaire. The study found that the length of sleep and the chronotype of the inhabitants surveyed in Northern European Russia depend on age, sex, type of settlement, and place of residence. The time of sunrise was a stronger predictor of sleep length and chronotype than the time of sunset and day length. A later chronotype and shorter sleep length were found for the subjects during the equinox (sunrise at 06:00 h) than under long-photoperiod conditions (sunrise at 04:00-05:00 h). During short-photoperiod conditions (sunrise at 07:00-10:00 h), no significant changes in the self reported sleep-wake rhythm were found. The time of sunrise had the strongest impact on the sleep-wake rhythm of 30- to 97-yr-old persons. Sunrise had a stronger influence on chronotype and sleep length in January to May, when the days become longer, than in October to December, when the days become shorter. Age- and season-associated changes were found in the entrainment of the sleep wake rhythm by photoperiod in the North. PMID- 22080736 TI - Light exposure among adolescents with delayed sleep phase disorder: a prospective cohort study. AB - The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n=16, 15.3+/-1.8 yrs) and unaffected controls (n=22, 13.7+/-2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00 h and 05:00 to 14:00 h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p< .02, 22:00-02:00 h) and less morning (p .05, 08:00-09:00 h and 10:00-12:00 h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p< .03, 5-7 h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p< .001 and p= .02, respectively) and morning (p= .01 and p< .001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p< .001). Increased total sleep time also correlated with increased exposure during the 9 h before sleep onset (p= .01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p< .001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD. PMID- 22080738 TI - Ring the bell for Matins: circadian adaptation to split sleep by cloistered monks and nuns. AB - Cloistered monks and nuns adhere to a 10-century-old strict schedule with a common zeitgeber of a night split by a 2- to 3-h-long Office (Matins). The authors evaluated how the circadian core body temperature rhythm and sleep adapt in cloistered monks and nuns in two monasteries. Five monks and five nuns following the split-sleep night schedule for 5 to 46 yrs without interruption and 10 controls underwent interviews, sleep scales, and physical examination and produced a week-long sleep diary and actigraphy, plus 48-h recordings of core body temperature. The circadian rhythm of temperature was described by partial Fourier time-series analysis (with 12- and 24-h harmonics). The temperature peak and trough values and clock times did not differ between groups. However, the temperature rhythm was biphasic in monks and nuns, with an early decrease at 19:39 +/- 4:30 h (median +/- 95% interval), plateau or rise of temperature at 22:35 +/- 00:23 h (while asleep) lasting 296 +/- 39 min, followed by a second decrease after the Matins Office, and a classical morning rise. Although they required alarm clocks to wake-up for Matins at midnight, the body temperature rise anticipated the nocturnal awakening by 85 +/- 15 min. Compared to the controls, the monks and nuns had an earlier sleep onset (20:05 +/- 00:59 h vs. 00:00 +/- 00:54 h, median +/- 95% confidence interval, p= .0001) and offset (06:27 +/- 0:22 h, vs. 07:37 +/- 0:33 h, p= .0001), as well as a shorter sleep time (6.5 +/- 0.6 vs. 7.6 +/- 0.7 h, p= .05). They reported difficulties with sleep latency, sleep duration, and daytime function, and more frequent hypnagogic hallucinations. In contrast to their daytime silence, they experienced conversations (and occasionally prayers) in dreams. The biphasic temperature profile in monks and nuns suggests the human clock adapts to and even anticipates nocturnal awakenings. It resembles the biphasic sleep and rhythm of healthy volunteers transferred to a short (10-h) photoperiod and provides a living glance into the sleep pattern of medieval time. PMID- 22080740 TI - Higher environmental temperature and global radiation are correlated with increasing suicidality--a localized data analysis. AB - Suicide rate follows a seasonal pattern that is related to rising air temperature and global radiation. These findings are reproducible within different climatic regions. Numerous studies have attempted to explain this peak in relation to weather. However, many of these studies did not use meteorological data representative of the site of the suicide or attempted suicide, resulting in limitations of the findings. Previous studies also suffered from limitations in the methods of data analysis. The current study examined the relationship between weather, i.e., solar radiation, air temperature, and the rate of suicides and suicidality in the area of Mittelfranken, Germany, using regional meteorological data. Statistical risk estimation revealed associations between higher global radiation and air temperatures on the day of and day before suicide acts. The results could be of interest for general suicide prevention strategies. Future studies should examine additional possible factors of influence and concentrate on a strict standardized study design. The aim is to obtain reproducible data of the seasonal influences on suicide behavior, allowing for the comparison of data from different meteorological regions and patient subgroups. PMID- 22080739 TI - Seasonality of retinal detachment incidence and its associations with climate: an 11-year nationwide population-based study. AB - This study aimed to examine the seasonal variability of retinal detachment (RD) in Taiwan by using an 11-yr nationwide population database. This study also investigated the association of weather conditions, i.e., ambient temperature, relative humidity, rainfall, monthly hours of sunshine, and atmospheric pressure, with RD. Data were retrospectively collected from the Taiwan National Health Insurance Research Database. The study sample included 23 718 RD hospitalizations between January 1999 and December 2009. The incidence rate of RD/100 000 people over the 132 months was computed according to sex and age groupings of <20, 20 39, 40-59, and >=60 yrs. Then, the association between climatic factors and the monthly RD incidence rate was examined. The ARIMA (autoregressive integrated moving average) method was also employed to test the seasonality of RD incidence rates and their association with climatic factors. The annual RD incidence rates were between 7.8 and 10.8 cases/100 000 people during the study period. A fairly similar seasonal pattern of monthly RD incidence rates was apparent for males and females and males and females combined. Rates were highest August through October, decreasing in November, and lowest in February. After adjusting for time, trend, and month, the ARIMA regression models for the male, female, and males and females combined consistently revealed the monthly RD incidence rate was significantly and positively associated with ambient temperature, but negatively associated with atmospheric pressure. The authors conclude that the monthly RD incidence rates were significantly associated with seasonality. The monthly RD incidence rates were positively associated with ambient temperature and negatively associated with atmospheric pressure. PMID- 22080742 TI - Tissue-dependent alterations of the clock gene expression rhythms in leptin resistant Zucker diabetic fatty rats. AB - Recent studies have demonstrated that circadian clocks are impaired in liver and adipose tissue of both leptin-deficient ob/ob and leptin-resistant KK-A(y) mice. Because impairment of peripheral clocks precedes metabolic abnormalities in ob/ob mice, leptin signaling might be important for modulating peripheral clocks. To assess this hypothesis, the authors determined daily mRNA expression profiles of clock genes Clock, Arntl, Per1, Per2, Cry1, Dbp, and Nr1d1 in several tissues of leptin-receptor-deficient Zucker diabetic fatty (ZDF) rats. Transcript levels of some of these genes around the respective peak times decreased significantly in the liver, but not in the suprachiasmatic nucleus, mesenteric adipose tissue, and heart, compared to those in control rats. In contrast, mRNA levels of Per1 and Dbp around the peak time increased in the aorta of ZDF rats. However, expression rhythms of these clock genes in serum-stimulated cultured cells isolated from the aorta of ZDF rats were quite similar to those in serum-stimulated aortic cells of control rats. These results show that systemic leptin signaling defect influences peripheral clocks in a tissue-dependent manner, suggesting the possibility that leptin indirectly modulates the clocks in at least a subset of peripheral tissues. PMID- 22080741 TI - Diurnal variations of plasma homocysteine, total antioxidant status, and biological markers of muscle injury during repeated sprint: effect on performance and muscle fatigue--a pilot study. AB - The aim of this study was (i) to evaluate whether homocysteine (Hcy), total antioxidant status (TAS), and biological markers of muscle injury would be affected by time of day (TOD) in football players and (ii) to establish a relationship between diurnal variation of these biomarkers and the daytime rhythm of power and muscle fatigue during repeated sprint ability (RSA) exercise. In counterbalanced order, 12 football (soccer) players performed an RSA test (5 x[6 s of maximal cycling sprint + 24 s of rest]) on two different occasions: 07:00 08:30 h and 17:00-18:30 h. Fasting blood samples were collected from a forearm vein before and 3-5 min after each RSA test. Core temperature, rating of perceived exertion, and performances (i.e., Sprint 1, Sprint 2, and power decrease) during the RSA test were significantly higher at 17:00 than 07:00 h (p < .001, p < .05, and p < .05, respectively). The results also showed significant diurnal variation of resting Hcy levels and all biological markers of muscle injury with acrophases (peak times) observed at 17:00 h. These fluctuations persisted after the RSA test. However, biomarkers of antioxidant status' resting levels (i.e., total antioxidant status, uric acid, and total bilirubin) were higher in the morning. This TOD effect was suppressed after exercise for TAS and uric acid. In conclusion, the present study confirms diurnal variation of Hcy, selected biological markers of cellular damage, and antioxidant status in young football players. Also, the higher performances and muscle fatigue showed in the evening during RSA exercise might be due to higher levels of biological markers of muscle injury and lower antioxidant status at this TOD. PMID- 22080743 TI - Implementing secure laptop-based testing in an undergraduate nursing program: a case study. AB - This article presents the implementation of secure laptop-based testing in an undergraduate nursing program. Details on how to design, develop, implement, and secure tests are discussed. Laptop-based testing mode is also compared with the computer-laboratory-based testing model. Five elements of the laptop-based testing model are illustrated: (1) it simulates the national board examination, (2) security is achievable, (3) it is convenient for both instructors and students, (4) it provides students hands-on practice, (5) continuous technical support is the key. PMID- 22080744 TI - Creating an ICNP subset: children with HIV/AIDS in developing countries. AB - Since 1993, the International Classification of Nursing Practice has evolved as a unified language for global nursing diagnoses/outcomes and interventions. It contains 5148 terms. Population- or condition-specific subsets of terms facilitate easier and consistent use of the International Classification of Nursing Practice. One condition, care of children in developing countries with HIV/AIDS, is listed by the World Health Organization as a world health priority. In this study, the investigators identified nursing diagnoses/outcomes and intervention terms used by nurses for this population and mapped the terms to the International Classification of Nursing Practice. Terms represent healthcare at different phases along a continuum: health promotion, health maintenance, acute conditions, chronic conditions, and end-of-life care with the child as the focus surrounded by family, community, and culture. In the analysis, the investigators' process is compared with the one outlined in the Guidelines for International Classification of Nursing Practice Catalogue Development, and the match of each local and International Classification of Nursing Practice term is categorized as perfect fit, conceptual fit, partial fit, or unable to fit. A total of 53 nursing diagnosis/outcome terms and 85 intervention terms make up the subset. Eighty-two percent of local terms mapped at least partially to International Classification of Nursing Practice. PMID- 22080745 TI - Development and pilot test of a culturally sensitive CD-ROM for hypertensive, older Chinese immigrants. AB - Hypertension control remains an issue for older Chinese immigrants because of the unique cultural health practices they use to manage their hypertension. Limited health education information on how to manage hypertension is available in Chinese. Because San Francisco has a large population of older Chinese immigrants, development of culturally sensitive educational material is important to help this population to achieve better blood pressure control. The purpose of this study was to develop and pilot test an innovative, culturally based CD-ROM with a focus on hypertension education and management, directed to the older Chinese immigrant population. The results of this pilot study found that the content of CD-ROM was culturally acceptable for the target population. Given a lack of educational material in Chinese in the United States, this CD-ROM has a potential to be used for a large population of Chinese elders in the United States. PMID- 22080746 TI - Comparative study of baccalaureate nursing student self-efficacy before and after simulation. AB - Evaluation of learning and the development of prelicensure nursing education include an exploration of new teaching models and techniques for student learning assessment. The utilization of high-fidelity human simulation in nursing provides nursing faculty and students the opportunity to expand the boundaries of conventional learning from an instructional paradigm to a blending of modalities that enrich the student experience and provide an avenue for self-determined learning. The inception of computer-generated high-fidelity human simulation technology into the undergraduate nursing curriculum generated this correlation study, which examined two separate groups of senior baccalaureate nursing students' reported self-efficacy for providing family-centered care. This research examined each group of students' reported self-efficacy on the first day of the pediatric semester before and after simulation and on the last day of the pediatric semester before and after simulation. In addition, the relationship between two senior baccalaureate nursing student groups' reported self-efficacy at four data points was examined. The concluding data identified that senior baccalaureate nursing students have unrealistic self-assessments of their clinical knowledge and nursing performance capabilities before simulation scenario participation. The perceived ability of undergraduate students to self identify their previously acquired knowledge and transferable clinical reasoning to family-centered situations is inaccurate. Human simulators are an effective teaching and learning modality in measuring factors that affect student outcomes. PMID- 22080747 TI - Quality of life in older Chinese-speaking adults with hearing impairment. AB - PURPOSE: General and hearing-specific health-related quality of life (HRQoL) was examined in elderly Chinese with hearing impairment. METHODS: Sixty-four Chinese speakers aged >=65 years and did not use hearing aids were evaluated using Chinese versions of the Short-Form 36 health survey (SF-36) and the Hearing Handicap Inventory for the Elderly (Screening Version) (HHIE-S). Results on the SF-36 were compared to norms obtained in a general elderly Chinese population. The relationships between HRQoL and degree of hearing impairment, and between SF 36 and HHIE-S were also evaluated. RESULTS: Elderly Chinese speakers with hearing impairment rated six of the eight scales of the SF-36 poorer, compared to a general elderly Chinese population. When average hearing impairment in the better ear exceeded 40 dB HL, SF-36 ratings were poorer than those with better hearing. Poorer better ear hearing was significantly related to poorer ratings on the Vitality scale of the SF-36 and the three scales of the HHIE-S, after controlling for age, gender and number of coexisting chronic health problems. Ratings on SF 36 and HHIE-S did not correlate. CONCLUSION: Elderly Chinese who are hearing impaired experienced poorer general and hearing-specific HRQoL, and HRQoL is reduced further among those with greater hearing impairment. PMID- 22080748 TI - Can magnetic targeting of magnetically labeled circulating cells optimize intramyocardial cell retention? AB - Therapeutic intracavitary stem cell infusion currently suffers from poor myocardial homing. We examined whether cardiac cell retention could be enhanced by magnetic targeting of endothelial progenitor cells (EPCs) loaded with iron oxide nanoparticles. EPCs were magnetically labeled with citrate-coated iron oxide nanoparticles. Cell proliferation, migration, and CXCR4 chemokine receptor expression were assessed in different labeling conditions and no adverse effects of the magnetic label were observed. The magnetophoretic mobility of labeled EPCs was determined in vitro, with the same magnet as that subsequently used in vivo. Coronary artery occlusion was induced for 30 min in 36 rats (31 survivors), followed by 20 min of reperfusion. The rats were randomized to receive, during brief aortic cross-clamping, direct intraventricular injection of culture medium (n = 7) or magnetically labeled EPCs (n = 24), with (n = 14) or without (n = 10) subcutaneous insertion of a magnet over the chest cavity (n = 14). The hearts were explanted 24 h later and engrafted cells were visualized by magnetic resonance imaging (MRI) of the heart at 1.5 T. Their abundance in the myocardium was also analyzed semiquantitatively by immunofluorescence, and quantitatively by real-time polymerase chain reaction (RT-PCR).Although differences in cell retention between groups failed to be statistically significant using RT-PCR quantification, due to the variability of the animal model, immunostaining showed that the average number of engrafted EPCs was significantly ten times higher with than without magnetic targeting. There was thus a consistent trend favoring the magnet-treated hearts, thereby suggesting magnetic targeting as a potentially new mean of enhancing myocardial homing of intravascularly delivered stem cells. Magnetic targeting has the potential to enhance myocardial retention of intravascularly delivered endothelial progenitor cells. PMID- 22080749 TI - Technology and innovation: 2010 a year in review. AB - The following commentary provides a discussion of the articles published in Technology and Innovation in 2010 and where possible places them into context with those reported in Cell Transplantation. These articles can be divided into the following topics: a) models for innovation and technological commercialization, b) the ethical and legal consequences of the emergence of new technologies, c) research on novel technologies and methods, and d) the difficulties involved in peer review and scientific assessment. The articles shed light on the effects of technological innovation and commercialization on scientific ethical regulation, the establishment of legal standards for the protection of intellectual property, and the development of financial models. PMID- 22080750 TI - Prostaglandin E2 enhances interleukin-8 production via EP4 receptor in human pulmonary microvascular endothelial cells. AB - Prostaglandin E(2) (PGE(2)) is a bioactive prostanoid implicated in the inflammatory processes of acute lung injury/acute respiratory distress syndrome. This study investigated whether PGE(2) can induce production of interleukin (IL) 8, the major chemokine for neutrophil activation, from human pulmonary microvascular endothelial cells (HPMVECs). PGE(2) significantly enhanced IL-8 protein production with increases in IL-8 mRNA expression and intracellular cAMP levels. HPMVECs expressed only EP4 receptor mRNA. The PGE(2) effects were mimicked by a selective EP4 receptor agonist, ONO-AE1-329, and inhibited by a selective EP4 receptor antagonist, ONO-AE3-208, or a protein kinase A inhibitor, Rp-adenosine 3',5'-cyclic monophosphorothioate triethylamine salt. The specific agonist for EP1, EP2, or EP3 receptor did not induce IL-8 production. PGE(2) induced IL-8 production was accompanied by p38 phosphorylation and was significantly inhibited by a p38 inhibitor, SB-203580, but not by an ERK1/2 inhibitor, U-0126, or a JNK inhibitor, SP-600125. Additionally, PGE(2) increased cyclooxygenase-2 expression with no change in constitutive cyclooxygenase-1 expression, suggesting possible involvement of an autocrine or paracrine manner. In conclusion, PGE(2) enhances IL-8 production via EP4 receptor coupled to G(s) protein in HPMVECs. Activation of the cAMP/protein kinase A pathway, followed by p38 activation, is essential for these mechanisms. Because neutrophils play a critical role in the inflammation of acute lung injury/acute respiratory distress syndrome, IL-8 released from the pulmonary microvasculature in response to PGE(2) may contribute to pathophysiology of this disease. PMID- 22080752 TI - The role of low-level lactate production in airway inflammation in asthma. AB - Warburg and coworkers (Warburg O, Posener K, Negelein E. Z Biochem 152: 319, 1924) first reported that cancerous cells switch glucose metabolism from oxidative phosphorylation to aerobic glycolysis, and that this switch is important for their proliferation. Nothing is known about aerobic glycolysis in T cells from asthma. The objective was to study aerobic glycolysis in human asthma and the role of this metabolic pathway in airway hyperreactivity and inflammation in a mouse model of asthma. Human peripheral blood and mouse spleen CD4 T cells were isolated by negative selection. T cell proliferation was measured by thymidine incorporation. Cytokines and serum lactate were measured by ELISA. Mouse airway hyperreactivity to inhaled methacholine was measured by a FlexiVent apparatus. The serum lactate concentration was significantly elevated in clinically stable asthmatic subjects compared with healthy and chronic obstructive pulmonary disease controls, and negatively correlated with forced expiratory volume in 1 s. Proliferating CD4 T cells from human asthma and a mouse model of asthma produced higher amounts of lactate upon stimulation, suggesting a heightened glycolytic activity. Lactate stimulated and inhibited T cell proliferation at low and high concentrations, respectively. Dichloroacetate (DCA), an inhibitor of aerobic glycolysis, inhibited lactate production, proliferation of T cells, and production of IL-5, IL-17, and IFN-gamma, but it stimulated production of IL-10 and induction of Foxp3. DCA also inhibited airway inflammation and hyperreactivity in a mouse model of asthma. We conclude that aerobic glycolysis is increased in asthma, which promotes T cell activation. Inhibition of aerobic glycolysis blocks T cell activation and development of asthma. PMID- 22080753 TI - Dominant factors affecting temperature rise in simulations of human thermoregulation during RF exposure. AB - Numerical models of the human thermoregulatory system can be used together with realistic voxel models of the human anatomy to simulate the body temperature increases caused by the power absorption from radio-frequency electromagnetic fields. In this paper, the Pennes bioheat equation with a thermoregulatory model is used for calculating local peak temperatures as well as the body-core temperature elevation in a realistic human body model for grounded plane-wave exposures at frequencies 39, 800 and 2400 MHz. The electromagnetic power loss is solved by the finite-difference time-domain (FDTD) method, and the discretized bioheat equation is solved by the geometric multigrid method. Human thermoregulatory models contain numerous thermophysiological and computational parameters--some of which may be subject to considerable uncertainty--that affect the simulated core and local temperature elevations. The goal of this paper is to find how greatly the computed temperature is influenced by changes in various modelling parameters, such as the skin blood flow rate, models for vasodilation and sweating, and clothing and air movement. The results show that the peak temperature rises are most strongly affected by the modelling of tissue blood flow and its temperature dependence, and mostly unaffected by the central control mechanism for vasodilation and sweating. Almost the opposite is true for the body core-temperature rise, which is however typically greatly lower than the peak temperature rise. It also seems that ignoring the thermoregulation and the blood temperature increase is a good approximation when the local 10 g averaged specific absorption rate is smaller than 10 W kg(-1). PMID- 22080754 TI - Effect of mosquito mats (pyrethroid-based) vapor inhalation on rat brain cytochrome P450s. AB - The effect of transfluthrin (TF) or D-allethrin (DA) pyrethroid (PYR) vapors, often contained as main ingredients in two commercially available mosquito repellent mats, on cytochrome P450 (CYP) enzymes of rat brain and liver was assessed. Immunodetection of CYP2E1 and CYP3A2 proteins revealed their induction in cerebrum and cerebellum, but not in liver microsomes of rats exposed by inhalation to TF or DA. This overexpression of proteins correlated with an increase of their catalytic activities. The specifically increased expression of CYP isoenzymes, due to PYR exposure in the rat brain, could perturb the normal metabolism of endogenous and xenobiotic compounds and leads to increased risks of neurotoxicity by bioactivation, lipid peroxidation and DNA damage. PMID- 22080755 TI - MyelomA Genetics International Consortium. AB - While the etiology of multiple myeloma (MM) is largely unknown, evidence for an inherited genetic susceptibility is provided by the two-fold increased risk of the disease seen in first-degree relatives of cases of MM. It is likely that part of this heritable risk is a consequence of the co-inheritance of low-risk genetic variants. The accumulated experience to date in identifying risk variants for other tumors has highlighted difficulties in conducting statistically and methodologically rigorous studies. The MyelomA Genetics International Consortium (MAGIC) includes 16 research groups in Europe, Asia, Australasia, the Middle East and the Americas engaged in studying the genetics of MM. The first goal of MAGIC is to identify and characterize common genetic variants for MM through association-based analyses. Here, we review the rationale for identifying genetic risk variants for MM and our proposed strategy for establishing MAGIC. PMID- 22080756 TI - Vascular access devices in leukemia: a retrospective review amongst patients treated at the Ottawa Hospital with induction chemotherapy for acute leukemia. AB - Patients with acute leukemia require reliable central vascular access to ensure delivery of intravenous therapy. Peripherally inserted central catheters (PICCs) and Hickman((r)) catheters are two commonly inserted central vascular catheters (CVCs), providing access to the central vascular space. While there have been reports describing individual center experiences, no one has compared the two devices, retrospectively or prospectively. We analyzed patients diagnosed with acute leukemia between September 1996 and April 2009, who had a PICC or Hickman(r), received induction chemotherapy and survived at least 20 days. Prior to 1 January 2007, PICCs were inserted by palpation (PICC-palp) and Hickman((r)) catheters were inserted surgically (H-Surg). After this date, PICCs were inserted by ultrasound (PICC-U/S) and Hickman(") catheters were inserted by interventional radiology (H-IR). Fifty-five patients had a Hickman((r)) catheter (18 H-Surg, 37 H-IR) and 92 patients had a PICC (69 PICC-palp, 23 PICC-U/S). Significant improvements from H-Surg to H-IR catheters include the reduction in exit-site inflammation and infection (27.8% to 5.4%) and in bacteremic episodes (72.2% to 27.0%). Compared to PICC-U/S, H-IR had fewer cases of thrombophlebitis (0.0% vs. 8.7%); H-IR also required fewer instillations of a thrombolytic agent than the PICC-U/S (8.1% vs. 69.6%). Both CVCs have shown improvements from pre- to post 2007 insertion methods. Our data suggest that there were fewer complications with post-2007 Hickman((r)) catheters compared to PICCs, suggesting that Hickman(r) catheters provide a more reliable central vascular access in these patients. PMID- 22080759 TI - An ab initio molecular dynamics study of iron phases at high pressure and temperature. AB - The crystal structure of iron, the major component of the Earth's inner core (IC), is unknown for the IC high pressure (P; 3.3-3.6 Mbar) and temperature (T; 5000-7000 K). There is mounting evidence that the hexagonal close-packed (hcp) phase of iron, stable at the high P of the IC and a low T, might be unstable under the IC conditions due to the impact of high T and impurities. Experiments at the IC P and T are difficult and do not provide a conclusive answer as regards the iron stability at the pressure of the IC and temperatures close to the iron melting curve. Recent theory provides contradictory results regarding the nature of the stable Fe phase. We investigated the possibility of body-centered cubic (bcc) phase stabilization at the P and T in the vicinity of the Fe melting curve by using ab initio molecular dynamics. Thermodynamic calculations, relying on the model of uncorrelated harmonic oscillators, provide nearly identical free energies within the error bars of our calculations. However, direct simulation of iron crystallization demonstrates that liquid iron freezes in the bcc structure at the P of the IC and T = 6000 K. All attempts to grow the hcp phase from the liquid failed. The mechanism of bcc stabilization is explained. This resolves most of the earlier confusion. PMID- 22080757 TI - A meta-analysis of TET2 mutations shows a distinct distribution pattern in de novo acute myeloid leukemia and chronic myelomonocytic leukemia. PMID- 22080758 TI - Inhibition of hedgehog signaling induces monocytic differentiation of HL-60 cells. AB - There is little evidence to demonstrate the importance of the Sonic hedgehog homolog (Shh) pathway to differentiation therapy in the treatment of hematological neoplasms. Here we characterize the changes in acute myelogenous leukemia (HL-60) cells after blocking the Shh pathway by an antagonist of Smoothened, cyclopamine. Cyclopamine induces apoptosis of HL-60 cells in a dose- and time-dependent manner with increased G0/G1 cycle fraction. Treatment with cyclopamine increases the expression of monocytic cell markers CD11b and CD14, but the expression of CD13, CD33 and CD38 is unchanged. The monocytic differentiation of HL-60 cells induced by cyclopamine is also evidenced by an increase in Egr-1 expression. Importantly, cyclopamine down-regulates the phosphorylation of Akt and ERK, but activates AMP-activated protein kinase (AMPK) signaling. Further investigations should determine the clinical application of modulating the Shh pathway in the treatment of hematological malignancies. PMID- 22080760 TI - Amyloid diagnosis, subcutaneous adipose tissue, immunohistochemistry and mass spectrometry. PMID- 22080761 TI - Proteomic typing of amyloid deposits in systemic amyloidoses. AB - Amyloidoses are characterized by the presence of extracellular amyloid deposits, constituted by fibrillar aggregates of misfolded proteins. Despite the similar morphologic appearance of fibrils, at least 28 different proteins have been detected as causative agents of human amyloidoses, 14 of which associated with systemic forms. Unequivocal typing of the amyloid deposits is a key step in the management of these diseases. Existing drawbacks of traditional, immunohistochemistry-based techniques have driven the search for alternative solutions for direct amyloid typing. Proteomics indicates the comprehensive study of the proteins in a biological sample, centered on analysis by mass spectrometry. The great potential of this approach in describing the composition of amyloid deposits and in studying the molecular features of the amyloidogenic precursors has become immediately clear and the introduction of proteomics in the clinical practice has revolutionized the field of amyloid typing. This review provides a critical overview of the various approaches that have been proposed in this specific context, along with a brief description of the proteomic methods for assessment of the circulating amyloidogenic proteins. PMID- 22080762 TI - The relative amounts of plasma transthyretin forms in familial transthyretin amyloidosis: a quantitative analysis by Fourier transform ion-cyclotron resonance mass spectrometry. AB - Familial transthyretin amyloidosis (ATTR) is a fatal autosomal dominant disease characterized by the formation of amyloid fibers, mainly composed of transthyretin (TTR). Protein aggregation and amyloid fiber formation are considered concentration dependent processes and since most ATTR patients are heterozygous it is crucial to determine the ratio between mutant and non-mutant TTR forms in human plasma. Using a high resolution mass spectrometry based approach we determined the ratio of TTR forms in ATTR patients, V30M mutation carriers, symptomatic and asymptomatic ones, as well as ATTR patients that received a wild type cadaveric liver transplant. Domino transplanted patients that received a liver from an ATTR patient were also investigated. We found that although wild type TTR is diminished in the plasma of non-transplanted ATTR patients comparatively to healthy subjects, the relationship with the V30M variant does not change with illness progression. Those who received a wild type liver showed no mutant protein while domino transplanted patients presented the same relative amount of V30M as found in asymptomatic and symptomatic individuals. The V30M to wild type TTR ratio in plasma is the same for all ATTR patients studied, showing no variation with disease clinical progression. Our results point to the involvement of additional non-genetic factors on the pathogenesis of this disease. PMID- 22080763 TI - Development of cardiomyopathy after liver transplantation in Swedish hereditary transthyretin amyloidosis (ATTR) patients. AB - BACKGROUND: Recent studies of liver transplanted (LTx) familial amyloidotic polyneuropathy (FAP) patients have shown a progression of cardiomyopathy in some patients after LTx, but knowledge of the underlying factors remains limited. METHODS: Seventy-five patients, who had undergone LTx from 1996 to 2008, were included. They had all been examined by echocardiography 1-16 months before LTx. Fifty-four had been re-examined 7-34 months, and forty-two 36-137 months after LTx. RESULTS: A significant increase in interventricular septum (IVS) thickness occurred after LTx (p < 0.01), particularly in males (p = 0.002) and late onset patients (p = 0.003). The development of post-LTx cardiomyopathy was related to patient's age at onset of the disease, male gender and pre-LTx IVS thickness. On multivariate regression analysis, however, age at onset was the only significant predictor for the development of cardiomyopathy (odds ratio = 1.14, 95% confident interval 1.01-1.30, p = 0.04). CONCLUSION: An increase of IVS thickness can be observed in FAP patients after LTx. Age at onset of the disease is the main predictor for increased IVS thickness and for the development of cardiomyopathy after liver transplantation. PMID- 22080764 TI - Abnormal heart rate variability in AA amyloidosis of familial Mediterranean fever. AB - BACKGROUND: A scarcity of data exists relating to the effect of amyloidosis of Familial Mediterranean fever (FMF) on the autonomic nervous system. Our aim was to further investigate the presence of dysautonomia in FMF-AA amyloidosis, using a comparative case series design. MATERIAL AND METHODS: The study group consisted of 40 patients with FMF: 20 without co-morbidities or amyloidosis and 20 in various stages of renal amyloidosis. Time domain and power spectral analyses of heart rate dynamics were performed according to accepted procedures. Findings were compared with 20 healthy control subjects. RESULTS: No statistically significant differences were found in any of the studied heart rate variability (HRV) parameters between patients with uncomplicated FMF and controls. In contrast, patients with progressive amyloidosis (post renal transplantation or on dialysis) had significantly lower HRV parameters compared to control subjects (i.e. mean low frequency power spectral components 104.30 ms2 vs. 172.09 ms2, p <0.05, mean standard deviation of all normal RR intervals 32.27 ms vs. 51.51 ms, p <0.05, mean HRV triangular index 9.08 vs. 15.82, p <0.05). The adjusted odds ratio was 14.5 (95%CI 1.21-165.03, p = 0.04) for HRV triangular index lower than 12.2 in the progressive amyloidosis group, 41.24 (95%CI 1.81-938.68, p = 0.02) for low frequency power spectral components values lower than 142.35 ms2, and 12.67 (95%CI 1.04-153.96, p = 0.04) for standard deviation of all normal RR intervals values lower than 40.15?ms. CONCLUSION: Amyloidosis of FMF, particularly at a progressive stage, is associated with HRV abnormalities suggestive of the presence of autonomic nervous system dysfunction. PMID- 22080765 TI - Participation-based therapy for children with physical disabilities. AB - PURPOSE: Optimizing home and community participation of children with physical disabilities is an important outcome of rehabilitation. METHOD: A review of literature identified research and theory on participation of children with physical disabilities. The authors' incorporated current knowledge to conceptualize the experience of optimal participation, formulate principles of participation-based physical and occupational therapy, and develop a five-step process for intervention. A case report was completed to illustrate application to practice. RESULTS: Optimal participation involves the dynamic interaction of determinants (attributes of the child, family, and environment) and dimensions (physical, social, and self engagement) of participation. Real-life experiences enable children to learn new activities and develop skills that optimize their participation and self-determination. Interventions are: goal-oriented, family centered, collaborative, strengths-based, ecological, and self-determined. A distinguishing feature of intervention is that the therapist's primary role is to support the child and family to identify challenges to participation and solutions to challenges. The therapist is a consultant, collaborating with the child, family, and community providers to share information, educate, and instruct in ways that build child, family, and community capacity. CONCLUSION: The model may have utility for collaboration with families and community providers, determining goals for participation, and providing evidence-informed interventions. PMID- 22080767 TI - Community partnership strategies: let's work from the same playbook. PMID- 22080766 TI - Reconstitution of the platelet glycoprotein Ib-IX complex in phospholipid bilayer Nanodiscs. AB - The glycoprotein Ib-IX (GPIb-IX) complex expressed on platelet plasma membrane is involved in thrombosis and hemostasis via the initiation of adhesion of platelets to von Willebrand factor (VWF) exposed at the injured vessel wall. While most of the knowledge of the GPIb-IX complex was obtained from studies on platelets and transfected mammalian cells expressing the GPIb-IX complex, there is not an in vitro membrane system that allows systematic analysis of this receptor. The phospholipid bilayer Nanodisc composed of a patch of phospholipid surrounded by membrane scaffold protein is an attractive tool for membrane protein study. We show here that the GPIb-IX complex purified from human platelets has been reconstituted into the Nanodisc. The Nanodisc-reconstituted GPIb-IX complex was able to bind various conformation-sensitive monoclonal antibodies. Furthermore, it bound to VWF in the presence of botrocetin with an apparent K(d) of 0.73 +/- 0.07 nM. The binding to VWF was inhibited by anti-GPIbalpha antibodies with epitopes overlapping with the VWF-binding site, but not by anti-GPIbbeta monoclonal antibody RAM.1. Finally, the Nanodisc-reconstituted GPIb-IX complex exhibited ligand binding activity similar to that of the isolated extracellular domain of GPIbalpha. In conclusion, the GPIb-IX complex in Nanodiscs adopts a native-like conformation and possesses the ability to bind its natural ligands, thus making a Nanodisc a suitable in vitro platform for further investigation of this hemostatically important receptor complex. PMID- 22080768 TI - Pioneers in health equity: lessons from the REACH communities. PMID- 22080772 TI - Case management intervention in cervical cancer prevention: the Boston REACH coalition women's health demonstration project. AB - BACKGROUND: The Boston REACH Coalition developed a case management intervention for Black women in primary care settings to identify and reduce medical and social obstacles to cervical cancer screening and following up abnormal results. METHODS: The 5-year intervention was evaluated among 732 Black women aged 18 to 75 who were at high risk for inadequate Pap smear screening and follow-up. Case managers provided social services referrals to address patient-identified social concerns (e.g., transportation, housing), as well as navigation to prompt screening and follow-up of abnormal tests. The three study aims were to (1) identify the social factors associated with Pap smear screening at baseline before intervention, (2) evaluate the correlation between exposure to case management intervention and achieving recommended Pap screening intervals, and (3) evaluate the correlation between exposure to case management intervention and having timely follow-up of abnormal Pap smear tests. RESULTS: We found that a lack of a regular clinical provider, concerns communicating with providers, poor self-rated health, and having less than a high school education were important correlates of recent Pap smear screening before the case management intervention. During the case management intervention, we found a significant increase in achieving recommended Pap smear screening intervals among women with a recent Pap smear at study entry (increasing from 52% in the first year to 80% after 4 or more years; p < .01), but not among women who entered the study without a recent Pap smear (increasing from 31% in the first year to 44% after 4 or more years; p = .39). During case management intervention, having social support for childcare was associated with regular screening among women without a recent Pap smear (odds ratio [OR], 3.52; 95% confidence interval [CI], 1.28-9.69). Insurance status was the key factor in timely clinically indicated follow-up of abnormal results (uninsured OR, 0.27; 95% CI, 0.08-0.86), rather than case management intervention. CONCLUSIONS: Exposure to case management was associated with regular Pap smear screening among women who recently engaged in screening. Future research should focus on systems changes to address social determinants of health, including strategies to facilitate screening for Black women without social support for childcare. To improve follow-up of abnormal results, financial access to care should be addressed. PMID- 22080771 TI - Evaluation of community-academic partnership functioning: center for the elimination of hepatitis B health disparities. AB - BACKGROUND: Process evaluation of community-academic partnership function and fidelity to principles of community-based participatory research (CBPR) is essential to achievement of intermediate and long term partnership goals. OBJECTIVES: This article describes the evaluation of B Free CEED, a community academic partnership created to address hepatitis health disparities in Asian American and Pacific Islander (API) communities. METHODS: A mixed methods approach with an online survey and qualitative key informant interviews was conducted with all partnership members at baseline and follow-up, 18 months later. RESULTS: Survey findings showed stability over time, with some consistent differences in community and academic perspectives. Academic members were somewhat more satisfied with the partnership functioning. Key informant interviews provided contextual data key to further defining partnership functioning. CONCLUSIONS: Conducting ongoing partnership evaluations is necessary to reassess and align processes and protocols to enhance partnership functioning and strengthen group cohesion. PMID- 22080773 TI - A partnered approach for structured observation to assess the environment of a neighborhood with high diabetes rates. AB - BACKGROUND: The Communities IMPACT Diabetes Center uses partnered methods to address diabetes-related conditions among African Americans and Latinos in East Harlem, New York. OBJECTIVES: To describe a novel, partnered approach that integrates simultaneous structured observation by community and academic partners with "on-the-spot" resolution of differences to collect baseline data regarding the built and food environments in a two census tract area of East Harlem and present select findings. METHODS: We designed an environmental assessment to explore characteristics of the environment related to walking and eating. We paired community and academic partners to assess each block, resolve any differences, and report results. Nearly one year later, we surveyed the data collectors and analyzed responses using standard qualitative methods. RESULTS: Key themes included connection to and characteristics of the community; interactions with partners; surprises and learning, and aspects of data collection. All but the first were common to academic and community partners. Relationships between partners were generally amiable. Both community-"I think it was very helpful, we made sure neither of us made mistakes, and helped each other when we could"-and academic-"I really enjoyed it . . . I learned a lot about the areas I surveyed"-partners were complimentary. Community partners' strengths included local knowledge of the community, whereas academic partners' focus on adherence to the specifications was critical. Structured observation identified many sidewalks in disrepair or obstructed, few benches, and highly variable times allocated for pedestrians to cross at cross walks. CONCLUSIONS: The partnered data collection was both successful and formative, building additional relationships and further capacity for ongoing partnership. Community partners saw their community in a new way, seeing, "little things that are important but people don't pay attention to." Structured observations added to our understanding of how an environment may contribute to diabetes. PMID- 22080774 TI - The Asian American hepatitis B program: building a coalition to address hepatitis B health disparities. AB - BACKGROUND: Community coalitions are increasingly recognized as important strategies for addressing health disparities. By providing the opportunity to pool resources, they provide a means to develop and sustain innovative approaches to affect community health. OBJECTIVES: This article describes the challenges and lessons learned in building the Asian American Hepatitis B Program (AAHBP) coalition to conduct a community-based participatory research (CBPR) initiative to address hepatitis B (HBV) among New York City Asian-American communities. METHODS: Using the stages of coalition development as a framework, a comprehensive assessment of the process of developing and implementing the AAHBP coalition is presented. LESSONS LEARNED: Findings highlight the importance of developing a sound infrastructure and set of processes to foster a greater sense of ownership, shared vision, and investment in the program. CONCLUSION: Grassroots community organizing and campus-community partnerships can be successfully leveraged to address and prevent a significant health disparity in an underserved and diverse community. PMID- 22080776 TI - Collaborating to address infant mortality: lessons learned from the Brownsville action community for health equality. AB - BACKGROUND: Brownsville Action Community for Health Equality (BACHE) is a coalition-based, service system change pilot for African American and Puerto Rican women of Brownsville, a community within Brooklyn, New York, with disproportionately high rates of infant mortality. OBJECTIVES: Identify "lessons learned" from the implementation phase of a 5-year pilot project that employs a community-based participatory (CBPR) approach to reducing risk factors for infant mortality. METHODS: Nineteen semi-structured interviews were conducted with BACHE's partners throughout 2010. Sessions were audiotaped and transcribed. Data was incorporated into a framework based on grounded theory and interpreted by project partners. RESULTS: Lessons learned related to engaging partners, leveraging community resources, dealing with highly structured institutions, measuring progress, and promoting and sustaining system change. CONCLUSION: A service system change pilot like BACHE requires: social capital, capable partners, a strong coalition, flexibility of approach, internal champions, systems knowledge, awareness of policy, and strong community involvement. PMID- 22080775 TI - Cardiovascular knowledge among urban American Indians and Alaska Natives: first steps in addressing cardiovascular health. AB - BACKGROUND: Cardiovascular disease (CVD) is common among American Indians/Alaska Natives (AI/ANs). Given limited access to health care, urban AI/ANs may be at particular risk. Lack of available data, however, limits our understanding of cardiovascular health in this population. OBJECTIVES: We conducted a survey to characterize CVD-related knowledge, behavior, and risk of urban AI/ANs. Results related to knowledge are reported. METHODS: In collaboration with the Indian clinics in two urban communities, we surveyed 298 AI/ANs. RESULTS: Respondents recognized approximately half of the symptoms of heart attack and stroke, and were significantly less likely to recognize each symptom than reported in national studies using the same items. General CVD knowledge (e.g., risks of high blood pressure) was stronger, although areas for improvement were noted. CONCLUSIONS: Urban AI/ANs would benefit from efforts to enhance CVD knowledge. These preliminary data are providing the foundation for community-based efforts to address CVD risk among urban AI/ANs. PMID- 22080777 TI - Instant Recess(r): a practical tool for increasing physical activity during the school day. AB - BACKGROUND: An increased prevalence of overweight/obesity among children has led to school district level policies to increase physical activity (PA) among elementary school students. Interventions are needed that increase activity levels without sacrificing time spent in academics. OBJECTIVES: We evaluated a policy implementation intervention for to increase in-school PA in elementary schools in Forsyth County, North Carolina, in a randomized study with a delayed intervention control group. METHODS: The study included third- through fifth grade classrooms in eight elementary schools. Instant Recess(r) was used to introduce 10-minute PA breaks in classrooms on schedules determined by teachers. Direct observation was used to measure activity levels, other student behaviors, and teacher behaviors related to PA in the classrooms. RESULTS: Twenty-eight visits to schools were made during the spring and fall semesters of 2009. At baseline 11% to 44% of intervention and control schools were engaged in classroom based PA. PA increased from baseline to spring follow-up in intervention schools and was maintained the following fall. Control schools decreased PA from baseline to spring and increased PA once they began the intervention. Students in classrooms engaged in Instant Recess exhibited statistically significant increases in light (51%) and moderate-intensity (16%) PA and increases in time spent in on-task behavior (11%). Control schools experienced similar benefits after they began implementing Instant Recess. CONCLUSIONS: Instant Recess is useful for increasing PA and improving behavior among elementary school children. Additional research may be needed to understand how to create policies supporting classroom activity breaks and how to assess policy adherence. PMID- 22080778 TI - A community-engaged approach to select geographic areas for interventions to reduce health disparities. AB - BACKGROUND: While neighborhood-based approaches to eliminate health disparities are on the rise, there is little guidance on how researchers may engage with community partners to select geographic areas for interventions to reduce health disparities. We aimed to identify a small geographic area to target interventions to improve diabetes-related outcomes. OBJECTIVES: We describe lessons learned from a community-engaged approach to specify the geographic area of focus. METHODS: A community-academic partnership of more than 20 organizations collaborated to develop and employ a 5-stage process to specify a target area for diabetes preventions and control activities. LESSONS LEARNED: A coalition with local knowledge and ties to the community can develop criteria and direct a process leading to selection of a geographic area, increased research capacity, and strengthened relationships among partners. CONCLUSION: A participatory approach can be effective in defining a geographic area for targeting interventions to reduce health disparities. PMID- 22080779 TI - Partnering with REACH to create a "diabetes-friendly" restaurant: a restaurant owner's experience. AB - We describe a Latino restaurateur's perspectives and partnership with Seattle King County REACH to improve the healthfulness of his restaurant as a step toward tackling diabetes in his community. We interviewed the owner and reviewed other documentation to capture his perspectives and identify key elements in this restaurant intervention. The impact of diabetes in the owner's family and Latino community motivated him to make changes at his restaurant. If changes were successful, he hoped this would motivate other Latino restaurateurs to make similar changes. At his request, REACH gathered consumer feedback, provided diabetes education and nutritional guidance, and worked with him to develop simple, economically feasible, healthier items. Positive consumer response and media coverage motivated the owner to explore additional changes at his restaurant and encourage other restaurateurs to make healthful changes. This intervention illustrates the potential for local businesses to collaborate with community partners, like REACH, to promote healthy food environments. PMID- 22080780 TI - Personal stories: voices of Latino youth health advocates in a diabetes prevention initiative. AB - The YMCA-Silicon Valley Racial and Ethnic Approaches to Community Health (REACH) U.S. Proyecto Movimiento (PM) Action Community project is a community-based partnership that aims to reduce the prevalence of diabetes among Latinos in the Greater Gilroy, California, area by delivering a prevention campaign across generations. A critical component of PM has been the creation of a Youth Health Advocate (YHA) afterschool club at three public high schools in Gilroy. The YHAs, who are trained on health, nutrition, diabetes, basic leadership skills, and digital storytelling, are at the forefront of the campaign targeting Gilroy youth. In their own words, the YHAs describe why they decided to become a YHA, the positive health impact of YHA activities on themselves and their family, and the positive impact on burgeoning leadership skills. The voices of YHAs in this prevention campaigns have brought value to the PM evaluation, and this qualitative element bears further examination in other community-based prevention campaigns. PMID- 22080781 TI - A community mobilizes to end medical apartheid. AB - PROBLEM: People of color suffer worse health outcomes than their White counterparts due, in part, to limited access to high-quality specialty care. PURPOSE: This article describes the events that led to the Bronx Health REACH coalition's decision to file a civil rights complaint with the New York State Office of the Attorney General alleging that three academic medical centers in New York City discriminated on the basis of payer status and race in violation of Title VI of the Civil Rights Act of 1964, the Hill-Burton Act, New York State regulations, and New York City Human Rights Law. KEY POINTS: Although the problem has not yet been resolved, the related community mobilization efforts have raised public awareness about the impact of disparate care, strengthened the coalition's commitment to achieve health equality, and garnered support among many city and state legislators. CONCLUSION: Community groups and professionals with relevant expertise can tackle complex systemic problems, but they must be prepared for a long and difficult fight. PMID- 22080782 TI - Children's hospital boston community Asthma initiative: partnerships and outcomes advance policy change. AB - PROBLEM: Rates of poorly controlled asthma among low-income children, particularly racial and ethnic minorities, remain disproportionately high. Comprehensive asthma programs, including education, case management and home environmental interventions have reduced disparities. Few sustainable payment models exist. PURPOSE: The Children's Hospital Boston's Community Asthma Initiative (CAI) demonstrated dramatic reductions in hospitalizations and emergency department (ED) visits among African American and Latino patients with a return on investment (ROI) of 1.46. A strong coalition focused on sustainability plus CAI outcomes contributed to the state legislature's approving a bundled payment pilot for high-risk pediatric asthma patients on Medicaid/MassHealth. KEY POINTS: Cost-effective, comprehensive asthma programs and policy makers' interest in new payment models created an opportunity for a new payment approach for pediatric asthma care. CONCLUSION: A community coalition that successfully addresses asthma health disparities with a strong business case and program outcomes can be leveraged to persuade policy makers of the value of innovative financing strategies for asthma care. PMID- 22080783 TI - Podcast interview transcript. Interview by Leandris Liburd. PMID- 22080784 TI - Advanced light-entrained activity onsets and restored free-running suprachiasmatic nucleus circadian rhythms in per2/dec mutant mice. AB - Many behavioral and physiological processes display diurnal (24-h) rhythms controlled by an internal timekeeping system?the circadian clock. In mammals, a circadian pacemaker is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and synchronizes peripheral oscillators found in most other tissues with the external light-dark (LD) cycle. At the molecular level, circadian clocks are regulated by transcriptional translational feedback loops (TTLs) involving a set of clock genes. The mammalian core TTL includes the transcriptional modulators PER?(1?3) and CRY?(1/2) that inhibit their own expression by interaction with CLOCK/NPAS2 and BMAL1 (ARNTL). The basic helix-loop-helix transcription factors DEC1 (BHLHE40) and DEC2 (BHLHE41) can interact with this core TTL, forming an accessory feedback mechanism. The authors measured circadian locomotor behavior and clock gene expression in the SCN of Per2/Dec double- and triple-mutant mice to analyze the functional interaction of PER2 and DEC feedback on circadian pacemaker function in the SCN. The data suggest a synergistic interaction of Per2 and Dec1/2 in activity entrainment to a standard LD cycle, correlating with a cumulative deficiency in negative-masking capacities in Per2/Dec double- and triple-mutant mice and suggesting an involvement of Per2 Dec1/2 interactivity in activity-onset regulation and masking under LD, but not under constant conditions. In contrast, under constant darkness (DD) conditions, a deletion of either Dec1 or Dec2 partially rescued the Per2 mutant short period/arrhythmicity phenotype, accompanied by a restoration of time-of-day effects on clock gene expression in the SCN. Together, these results show an interaction of Per2 and Dec1/2 feedback processes in the SCN with differential modes of interactivity under entrained and free-run conditions. (Author correspondence: henrik.oster@mpibpc.mpg.de ). PMID- 22080785 TI - Sleep and academic performance in undergraduates: a multi-measure, multi predictor approach. AB - The present study examined the associations of sleep patterns with multiple measures of academic achievement of undergraduate university students and tested whether sleep variables emerged as significant predictors of subsequent academic performance when other potential predictors, such as class attendance, time devoted to study, and substance use are considered. A sample of 1654 (55% female) full-time undergraduates 17 to 25 yrs of age responded to a self-response questionnaire on sleep, academics, lifestyle, and well-being that was administered at the middle of the semester. In addition to self-reported measures of academic performance, a final grade for each student was collected at the end of the semester. Univariate analyses found that sleep phase, morningness/eveningness preference, sleep deprivation, sleep quality, and sleep irregularity were significantly associated with at least two academic performance measures. Among 15 potential predictors, stepwise multiple regression analysis identified 5 significant predictors of end-of-semester marks: previous academic achievement, class attendance, sufficient sleep, night outings, and sleep quality (R(2)=0.14 and adjusted R(2)=0.14, F(5, 1234)= 40.99, p < .0001). Associations between academic achievement and the remaining sleep variables as well as the academic, well-being, and lifestyle variables lost significance in stepwise regression. Together with class attendance, night outings, and previous academic achievement, self-reported sleep quality and self-reported frequency of sufficient sleep were among the main predictors of academic performance, adding an independent and significant contribution, regardless of academic variables and lifestyles of the students. PMID- 22080786 TI - Circadian preference and sleep-wake regularity: associations with self-report sleep parameters in daytime-working adults. AB - The aim of this study was to explore how interindividual differences in circadian type (morningness) and sleep timing regularity might be related to subjective sleep quality and quantity. Self-report circadian phase preference, sleep timing, sleep quality, and sleep duration were assessed in a sample of 62 day-working adults (33.9% male, age 23?48 yrs). The Pittsburgh Sleep Quality Index (PSQI) measured subjective sleep quality and the Sleep Timing Questionnaire (STQ) assessed habitual sleep latency and minutes awake after sleep onset. The duration, timing, and stability of sleep were assessed using the STQ separately for work-week nights (Sunday?Thursday) and for weekend nights (Friday and Saturday). Morningness-eveningness was assessed using the Composite Scale of Morningness (CSM). Daytime sleepiness was measured using the Epworth Sleepiness Scale (ESS). A morning-type orientation was associated with longer weekly sleep duration, better subjective sleep quality, and shorter sleep-onset latency. Stable weekday rise-time correlated with better self-reported sleep quality and shorter sleep-onset latency. A more regular weekend bedtime was associated with a shorter sleep latency. A more stable weekend rise-time was related to longer weekday sleep duration and lower daytime sleepiness. Increased overall regularity in rise-time was associated with better subjective sleep quality, shorter sleep onset latency, and higher weekday sleep efficiency. Finally, a morning orientation was related to increased regularity in both bedtimes and rise-times. In conclusion, in daytime workers, a morning-type orientation and more stable sleep timing are associated with better subjective sleep quality. (Author correspondence: asoehner@berkeley.edu ). PMID- 22080787 TI - When does stress end? Evidence of a prolonged stress reaction in shiftworking truck drivers. AB - This study aimed to analyze individual cortisol levels in relation to work conditions, sleep, and health parameters among truck drivers working day shifts (n = 21) compared to those working irregular shifts (n = 21). A total of 42 male truck drivers (39.8 (+/-) 6.2 yrs) completed questionnaires about sociodemographics, job content, work environment, health, and lifestyle. Rest activity profiles were measured using actigraphy, and cardiovascular blood parameters were collected. Salivary cortisol samples were obtained: (i) at waking time, (ii) 30?min after waking, and (iii) at bedtime, during both one workday and one day off from work. Irregular-shift workers, compared to day-shift workers, showed significantly higher waist-hip ratio, very-low-density lipoprotein (VLDL) cholesterol, tiredness after work, years working as a driver, truck vibration, and less job demand (p < .05). High cortisol levels in irregular-shift workers were correlated with certain stressors, such as short sleep duration and low job satisfaction, and to metabolic parameters, such as total cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), VLDL, and triglycerides. Day-shift workers had higher cortisol levels collected 30?min after waking (p = .03) and a higher cortisol awakening response (CAR; p = .02) during workdays compared to off days. Irregular-shift workers had higher cortisol levels on their off days compared to day-shift workers (p = .03). In conclusion, for the day-shift workers, a higher cortisol response was observed on workdays compared to off days. Although no direct comparisons could be made between groups for work days, on off days the irregular-shift workers had higher cortisol levels compared to day-shift workers, suggesting a prolonged stress response in the irregular-shift group. In addition, cortisol levels were correlated with stressors and metabolic parameters. Future studies are warranted to investigate further stress responses in the context of irregular work hours. PMID- 22080788 TI - Seasonality in the incidence of cervical carcinoma in teenagers and young adults in Northern England, 1968-2005. AB - Infection with human papillomavirus is an established risk factor for cervical carcinoma. However, the role of other environmental factors is less well established. To further investigate whether other agents may be involved, the authors have analyzed seasonal variation in cervical cancer with respect to month of birth and separately month of diagnosis. All 85 cases diagnosed in 15-24-yr olds during the period 1968-2005 were extracted from the specialist population based Northern Region Young Persons' Malignant Disease Registry. The chi-square heterogeneity test was used to assess overall nonuniform variation in month of birth and separately month of diagnosis. Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data using month of birth and month of diagnosis in separate models. Based on month of birth, there was statistically significant heterogeneity (p=.03) and a significant sinusoidal pattern, with an incidence peak involving births in the autumn months (p=.03). Based on month of diagnosis, there was marginally significant heterogeneity (p=.06). The evidence of seasonal variation around time of birth for cervical carcinoma is highly novel and suggests possible early etiological involvement of environmental factors. PMID- 22080789 TI - The CLOCK gene and mood disorders: a case-control study and meta-analysis. AB - The clock gene (CLOCK) is considered to be a good candidate gene for the pathophysiology of mood disorders, including bipolar disorder (BP) and major depressive disorder (MDD). rs1801260 (T3111C) has been detected at position 3111 in the CLOCK mRNA 3' untranslated region, and was reported to be associated with a substantial delay in preferred timing for activity and sleep in a human study. As for function, rs1801260 has been speculated to affect mRNA. Therefore, the authors investigated the association between the three tagging single-nucleotide polymorphisms (SNPs) (rs3736544, rs1801260, and rs3749474) in CLOCK and risk of BP (n=867) and MDD (n=139) compared to controls (n=889) in the Japanese population. In addition, we also performed an updated meta-analysis of nine published, genetic association studies investigating the relationship between rs1801260 and mood disorder risk, comprising 3321 mood disorders cases and 3574 controls. We did not detect any associations between tagging SNPs in CLOCK and BP or MDD in the allele, genotype, or haplotype analysis (global p(BP)=.605 and global p(MDD)=.211). Moreover, rs1801260 was also not associated with BP, MDD, or any mood disorders in the meta-analysis. In conclusion, these data suggest that CLOCK does not play a major role in the pathophysiology of mood disorders. PMID- 22080790 TI - Subcellular evidence for the involvement of peroxisomes in plant isoprenoid biosynthesis. AB - The role of peroxisomes in isoprenoid metabolism, especially in plants, has been questioned in several reports. A recent study of Sapir-Mir et al. revealed that the two isoforms of isopentenyl diphosphate (IPP) isomerase, catalyzing the isomerisation of IPP to dimethylallyl diphosphate (DMAPP) are found in the peroxisome. In this addendum, we provide additional data describing the peroxisomal localization of 5-phosphomevalonate kinase and mevalonate 5 diphosphate decarboxylase, the last two enzymes of the mevalonic acid pathway leading to IPP. This finding was reinforced in our latest report showing that a short isoform of farnesyl diphosphate, using IPP and DMAPP as substrates, is also targeted to the organelle. Therefore, the classical sequestration of isoprenoid biosynthesis between plastids and cytosol/ER can be revisited by including the peroxisome as an additional isoprenoid biosynthetic compartment within plant cells. PMID- 22080791 TI - The occurrence of a thylakoid-localized small zinc finger protein in land plants. AB - Previous studies showed that LOW QUANTUM YIELD OF PHOTOSYSTEM II 1 (LQY1), a small thylakoid zinc finger protein was involved in maintenance and repair of Photosystem II (PSII). Here the author provide additional evidence for the role of LQY1 in PSII maintenance and repair and further commentary on the occurrence of LQY1 protein among land plants. After exposure to high light, Arabidopsis thaliana mutants lacking functional LQY1 gene (At1g75690) are more photoinhibited than wild-type control plants; display higher total non-photochemical quenching and photoinhibitory quenching. These results are consistent with the initial observation that lqy1 mutants have lower PSII efficiency than wild-type plants after high-light treatment. The low-PSII-efficiency phenotype can be suppressed upon complementation of lqy1 mutants with the LQY1 gene from wild-type plants. This further demonstrates that LQY1 is important in maintaining the activity of photosystem II in Arabidopsis. LQY1 homologs are present in land plants but are absent from sequenced genomes of green algae and cyanobacteria, which may reflect plant adaptation to excess light stress during the transition to land. PMID- 22080792 TI - Fiducial registration error as a statistical process control metric in image guidance radiotherapy with fiducial markers. AB - Portal imaging of implanted fiducial markers has been in use for image-guided radiotherapy (IGRT) of prostate cancer, with ample attention to localization accuracy and organ motion. The geometric uncertainties in point-based rigid-body matching algorithms during localization of prostate fiducial markers can be quantified in terms of a fiducial registration error (FRE). In this study, the aim is to demonstrate how statistical process control (SPC) can be used to intercept potential problems with rigid-body matching algorithms in a retrospective study of FRE for a pilot cohort of 34 patients with fiducial markers. A procedure for estimating control parameters of a SPC control chart (x chart) from a small number of initial observations (N) of FRE was implemented. The sensitivity analysis of N on the number of 'in-control' and 'out-of-control' x-charts was also performed. Uncorrected rotational offsets of an individual patient were examined to elucidate possible correlations with the behaviours of an x-chart. Four specific types of qualitative x-chart behaviour have been observed. The number of out-of-control processes was insensitive to the choice of N, provided N >= 5. Residual errors of rigid-body registration were contributed from uncorrected rotational offsets in 5 out of 15 'out-of-control' x-charts. Out of-control x-charts were also shown to be correlated with potential changes in the IGRT processes, which may compromise the quality of the radiation treatment delivery. The SPC methodology, implemented in the form of individually customized x-charts, has been shown to be a useful tool for monitoring process reliability during fiducial-based IGRT for prostate cancer. PMID- 22080793 TI - Development and application of purified tissue dissociation enzyme mixtures for human hepatocyte isolation. AB - Human hepatocyte transplantation is gaining acceptance for the treatment of liver diseases. However, the reagents used to isolate hepatocytes from liver tissue are not standardized and show lot-to-lot variability in enzyme activity and endotoxin contamination. For clinical application, highly purified reagents are preferable to crude digest preparations. A purified tissue dissociating enzyme (TDE) preparation (CIzyme(TM) purified enzymes) was developed based on the enzyme compositions found in a superior lot of collagenase previously used by our group for human hepatocyte isolation. The performance of this enzyme preparation was compared to collagenase type XI on 110 liver cases by assessing hepatocyte yield, viability, and seven other functional assays that included plating efficiency, basal and induced CYP450 activities, phase II conjugation activity, and ammonia metabolism. No statistically significant difference was observed between these TDEs when they were used to isolate hepatocytes from liver resections or organ donor tissue on 54 hepatocyte isolations with type XI enzyme and 56 isolations using CIzyme(TM). These results show that a highly purified and defined TDE preparation can be formulated that provides excellent performance with respect to viability, yield, and functional activity of the isolated cells. In addition to reproducible formulation, these purified enzyme products have only 2-3% of the endotoxin of crude enzyme preparations. These results show that purified enzymes such as CIzyme(TM) will be a safe and effective for the isolation of human hepatocytes for clinical transplants. PMID- 22080794 TI - Full coverage for preventive medications after myocardial infarction. AB - BACKGROUND: Adherence to medications that are prescribed after myocardial infarction is poor. Eliminating out-of-pocket costs may increase adherence and improve outcomes. METHODS: We enrolled patients discharged after myocardial infarction and randomly assigned their insurance-plan sponsors to full prescription coverage (1494 plan sponsors with 2845 patients) or usual prescription coverage (1486 plan sponsors with 3010 patients) for all statins, beta-blockers, angiotensin-converting-enzyme inhibitors, or angiotensin-receptor blockers. The primary outcome was the first major vascular event or revascularization. Secondary outcomes were rates of medication adherence, total major vascular events or revascularization, the first major vascular event, and health expenditures. RESULTS: Rates of adherence ranged from 35.9 to 49.0% in the usual-coverage group and were 4 to 6 percentage points higher in the full coverage group (P<0.001 for all comparisons). There was no significant between group difference in the primary outcome (17.6 per 100 person-years in the full coverage group vs. 18.8 in the usual-coverage group; hazard ratio, 0.93; 95% confidence interval [CI], 0.82 to 1.04; P=0.21). The rates of total major vascular events or revascularization were significantly reduced in the full coverage group (21.5 vs. 23.3; hazard ratio, 0.89; 95% CI, 0.90 to 0.99; P=0.03), as was the rate of the first major vascular event (11.0 vs. 12.8; hazard ratio, 0.86; 95% CI, 0.74 to 0.99; P=0.03). The elimination of copayments did not increase total spending ($66,008 for the full-coverage group and $71,778 for the usual-coverage group; relative spending, 0.89; 95% CI, 0.50 to 1.56; P=0.68). Patient costs were reduced for drugs and other services (relative spending, 0.74; 95% CI, 0.68 to 0.80; P<0.001). CONCLUSIONS: The elimination of copayments for drugs prescribed after myocardial infarction did not significantly reduce rates of the trial's primary outcome. Enhanced prescription coverage improved medication adherence and rates of first major vascular events and decreased patient spending without increasing overall health costs. (Funded by Aetna and the Commonwealth Fund; MI FREEE ClinicalTrials.gov number, NCT00566774.). PMID- 22080795 TI - Was the black death in India and China? AB - Firsthand accounts of the Black Death in Europe and the Middle East and many subsequent historians have assumed that the pandemic originated in Asia and ravaged China and India before reaching the West. One reason for this conviction among modern historians is that the plague in the nineteenth century originated and did its worst damage in these countries. But a close examination of the sources on the Delhi Sultanate and the Yuan Dynasty provides no evidence of any serious epidemic in fourteenth-century India and no specific evidence of plague among the many troubles that afflicted fourteenth-century China. PMID- 22080796 TI - "Because of their praiseworthy modesty, they consult too late": regime of hope and cancer of the womb, 1800-1910. AB - The birth of the "do not delay" principle in cancer treatment has often been linked with developments in late nineteenth century: the rise of histology and cellular theory of malignancy that favored the definition of cancer as a local pathology, then the development of radical surgical techniques that transformed malignant tumors into a potentially curable condition. This text seeks to nuance this view. It points out important continuities in the understanding of the natural history of uterine cancers. At its center, the wish, already present in early nineteenth century, is to detect "early," that is, small and localized malignant lesions, then to extirpate or destroy these lesions before they become fully blown cancer. The long history of this particular regime of hope helps demonstrate why it is so difficult today to promote more nuanced views of the efficacy of early detection of malignant tumors. PMID- 22080797 TI - Local government health services in interwar England: problems of quantification and interpretation. AB - This article provides a critical discussion of recent work on local government health care and health services in interwar England. A literature review examines case study approaches and comparative quantitative surveys, highlighting conventional and revisionist interpretations. Noting the differing selection criteria evident in some works, it argues that studies based upon a limited number of personal health services provide an insufficient basis for assessing local health activity and policy. There follows a regional study demonstrating various discrepancies between health financing data in local sources and those in nationally collated returns. These in turn give rise to various problems of assessment and interpretation in works relying on the latter, particularly with respect to services for schoolchildren and long-stay patients. The case study points to the importance of integrating poor law medical services in evaluations, and of learning more about the role of government subsidy in supporting expanding services. PMID- 22080798 TI - Translating Western modernity: the first chinese hospital in america. AB - Since hospitals are often at the center of health care services, their foundation and evolution provides valuable insights into local political, economic, and cultural contexts. Based on Western and Chinese sources, this essay employs a transnational approach to explain the establishment of the Tung Wah or Oriental Dispensary in San Francisco. This article describes the institution's aims, financing, and combined operation of Western and Chinese medical staffs in an environment of racial discrimination and political power struggles, as well as deep social and cultural divisions during the early twentieth-century plague epidemic. PMID- 22080799 TI - American association for the history of medicine: report of the eighty-fourth annual meeting. PMID- 22080800 TI - Phonon dispersions in random alloys: a method based on special quasi-random structure force constants. AB - In an attempt to obtain reliable first-principles phonon dispersions of random alloys, we have developed a method to calculate the dynamical matrix, with respect to the wavevector space of the ideal lattice, by averaging over the force constants of a special quasi-random structure. Without additional approximations beyond standard density functional theory, the present scheme takes into account the local atomic position relaxations, the composition disorder, and the force constant disorder in a random alloy. Numerical results are presented for disordered Cu(3)Au, FePd, and NiPd and good agreement between the calculations and the inelastic neutron scattering data is observed. PMID- 22080801 TI - Determination of memantine in plasma and vitreous humour by HPLC with precolumn derivatization and fluorescence detection. AB - A new HPLC procedure with precolumn derivatization and rimantadine as the internal standard for determining memantine, a candidate agent for the treatment of glaucoma in plasma and vitreous humour, has been developed and validated. Precolumn derivatization was performed with 9-fluorenylmethyl-chloroformate chloride (FMOC-Cl) as the derivatization reagent and followed by a liquid-liquid extraction with n-hexane. Optimal conditions for derivatization were an FMOC-Cl concentration of 1.5 mM, a reaction time of 20 min, the temperature at 30 degrees C, the borate buffer pH 8.5, and a borate buffer-acetonitrile ratio of 1:1. The derivatives were analyzed by isocratic HPLC with the fluorescence detector lambdaex 260 nm lambdaem 315 nm on a Novapack C(18) reversed-phase column with a mobile phase of acetonitrile-water (73:27, v/v), 40 degrees C, and a flow rate of 1.2 mL/min. The linear range was 10-1000 ng/mL with a quantification limit of ~ 10 ng/mL for both types of samples. This analytical method may be suitable for using in ocular availability studies. PMID- 22080802 TI - A new HPLC-UV validated method for therapeutic drug monitoring of tyrosine kinase inhibitors in leukemic patients. AB - Development and validation of simple, rapid, and reliable high-performance liquid chromatography (HPLC)-UV method for quantification of major tyrosine kinase inhibitors, imatinib, dasatinib, and nilotinib, in human plasma is presented. Chromatographic separation of the drugs is achieved on an RP-C(18) column at flow rate of 0.9 mL/min at 35 degrees C; eluate is monitored at 267 nm. Mean intra-day and inter-day precision for all compounds are 2.5 and 13.3%; mean accuracy is 13.9%; extraction recovery ranges within 40.24 and 81.81%. Calibration curves range from 10 to 0.005 MUg/mL. Limits of detection are 10 ng/mL for imatinib and nilotinib, 50 ng/mL for dasatinib; limits of quantitation are 50 ng/mL for imatinib and nilotinib, 100 ng/mL for dasatinib. Although this method allows the detection of dasatinib, levels found in patients plasma are close to the limit of detection, then below the limit of quantitation. Quantification with HPLC-mass spectrometry, then, is required for dasatinib to give a correct evaluation. In conclusion, the sensitivity of this new method is sufficient to perform therapeutic monitoring and pharmacokinetic studies of imatinib and nilotinib but not dasatinib in CML patients. PMID- 22080803 TI - Pharmacological classification of drugs by principal component analysis applying molecular modeling descriptors and HPLC retention data. AB - Pharmacological classification of drugs by principal component analysis (PCA) based on molecular modeling and high-performance liquid chromatography (HPLC) retention data is proposed. First, a group of 20 drugs of recognized pharmacological classification are chromatographed in eight diversified HPLC systems, applying columns with octadecylsilanes, phosphatidylcholine, as well as alpha1-glycoprotein and albumin. Additionally, molecular modeling studies, based on the structural formula of the drugs considered, are performed. Sixteen structural descriptors are derived. A matrix of 20 * 24 HPLC data together with molecular parameters are subjected to principal component analysis, and this revealed five main factors with eigenvalues higher than 1. The first principal component (factor 1) accounted for 47.8% of the variance in the data, and the second principal component (factor 2) explained 21.0% of data variance. The total data variance was 82.6% and is explained by the first three factors. The clustering of drugs is in accordance with their pharmacological classification, which proved that the PCA of the HPLC retention data, together with their structural descriptors, allowed the drugs to be segregated accurately to their pharmacological properties. This may be of help in reducing the number of biological assays needed in the development of a new drug. PMID- 22080804 TI - UHPLC method for the simultaneous determination of beta-blockers, isoflavones, and flavonoids in human urine. AB - A simple method using solid-phase extraction (SPE) and ultra high-performance liquid chromatography (UHPLC) for the simultaneous determination of beta blockers, isoflavones, and flavonoids in human urine is developed. A statistical central composite design and response surface analysis is used to optimize the separation of the analytes. These multivariate procedures are efficient in determining the optimal separation condition using resolutions and retention time as responses. A gradient elution using a mobile phase consisting of 0.05% trifluoroacetic acid in water and acetonitrile is applied on a Hypersil GOLD column within a short analysis time of 4.5 min. UV detection was used to monitor the analytes. The suggested method was linear in a concentration range from 0.04 20.00 MUg/mL, depending on the compound. The limits of detection ranged from 8.9 to 66.2 ng/mL. The precision was lower than 2.74%, and the accuracy was between 0.01-3.65%. The Oasis HLB column, with the highest recoveries, is selected for the pre-concentration step. This present paper reports, for the first time, a method for the simultaneous determination of beta-blockers, isoflavones, and flavonoids in human urine samples. Furthermore, the developed method can also be applied to the routine determination of examined compounds concentrations in human urine. PMID- 22080805 TI - Development and validation of new assay method for the simultaneous analysis of diltiazem, metformin, pioglitazone and rosiglitazone by RP-HPLC and its applications in pharmaceuticals and human serum. AB - Simple, sensitive, rapid, and accurate high-performance liquid chromatographic (HPLC) method is developed and validated for the simultaneous determination of diltiazem, metformin, pioglitazone, and rosiglitazone hydrochloride in raw materials, their pharmaceutical formulations, and human serum. In HPLC, all the above drugs were chromatographed using acetonitrile-methanol-water (30:20:50, v/v, pH 2.59 +/- 0.02) as the mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The separation is carried out on a Hiber, 250-4.6 RP-18 column, equipped with a UV-vis detector at 230 nm. All the antidiabetic drugs eluted at different retention time and each showed a good resolution from diltiazem. The method is successfully applied to pharmaceutical formulations because no chromatographic interferences from the tablet excipients are found. The method is found to be linear, accurate, and precise with apposite detection and quantification limit. Suitability of the method for the quantitative determination of the drugs is proven by validation in accordance with the requirements laid down by International Conference on Harmonization (ICH) guidelines. The validation results, together with statistical treatment of the data, demonstrated the reliability of this method. PMID- 22080806 TI - A stability indicating HPLC method for the determination of electrochemically controlled release of risperidone. AB - A rapid stability indicating reversed-phase high-performance liquid chromatography (HPLC) method is developed for the determination of the electrochemically controlled risperidone release from a novel drug delivery system, based on the intrinsically conducting polymer (ICP), polypyrrole. The chromatographic separation was carried out on a C(18) column using acetonitrile potassium dihydrogen phosphate (45:55, v/v, pH 6.5; 0.05 M) as the mobile phase. The isocratic flow is at 1.0 mL/min, with a runtime of 6 min, and the UV detection is at 237 nm. This provided a calibration curve linear over the range of 1-100 MUg/mL. Intra-day and inter-day accuracy range between 98.4% and 102.6%, and the RSD for precision is <1.43%. The limit of detection and quantitation were determined to be 0.001 MUg/mL and 0.01 MUg/mL, respectively. The analytical method confirmed risperidone is stable for the oxidizing electric potential and the acidic environment involved during the manufacture and operation of the novel drug delivery system. The rate of risperidone release from polypyrrole depended on electrical stimulation applied to the polymer. This HPLC method is significantly faster than previously published methods and is the first to investigate the effect of an oxidizing potential on risperidone stability, which is essential for the evaluation of controlled delivery from an ICP-based system. PMID- 22080807 TI - RP-HPLC stability-indicating assay method for talinolol and characterization of its degradation products. AB - A reversed-phase high-performance liquid chromatographic method is developed and validated for the quantitative determination of talinolol and to characterize its degradation products. A very good resolution between peaks is achieved using a C18 column at 40 degrees C. The mobile phase comprises of a mixture of acetonitrile and potassium dihydrogen orthophosphate buffer (pH 4.4) in the ratio of 27:73 (v/v). The method is validated with respect to linearity, accuracy, precision, robustness, and forced degradation studies, which further proved the stability indicating power. During the forced degradation studies, talinolol is observed to be labile to hydrolytic stress and thermal stress (in the solution form). However, it is stable to the oxidative, photolytic, and thermal stress (in the solid form). The degraded products formed are investigated by electrospray ionization (ESI), time-of-flight mass spectrometry, nuclear magnetic resonance, and infrared spectroscopy. A possible degradation pathway is outlined based on the results. The method is found to be sensitive with a detection limit of 0.125 MUg/mL and a quantitation limit of 0.378 MUg/mL. The method is also demonstrated to be robust, as it is resistant to small variations of chromatographic variables such as pH, mobile phase composition, flow rate, and column temperature. PMID- 22080808 TI - A simple HPLC-DAD method for determination of adapalene in topical gel formulation. AB - A simple stability indicating high-performance liquid chromatography method for the analysis of adapalene in pharmaceutical gel formulation is developed and validated. An isocratic separation is performed using a Merck RP-8 (150 mm * 4.6 mm i.d., particle size 5 m) column and a mixture of acetonitrile water (67:33, v/v, pH adjusted to 2.5 with phosphoric acid) as the mobile phase. The detection is achieved with a photodiode array detector at 321 nm. The specificity of the method is verified by subjecting both the reference substance and the pharmaceutical form to hydrolytic, oxidative, photolytic, and thermal stress conditions. There is no interference from the excipients of the formulation on the determination of adapalene in gel. The response is linear over the concentration range of 8.0-16.0 MUg/mL (r > 0.999) with a limit of detection and quantification of 0.04 and 0.14 MUg/mL, respectively. The mean recovery is 100.8%. The RSD values for the intra- and inter-day precision studies are < 1.2%. The method is validated by reaching satisfactory results for linearity, selectivity, specificity, precision, accuracy, robustness, and system suitability. PMID- 22080809 TI - Development and validation of an LC-MS-MS method for the simultaneous determination of sulforaphane and its metabolites in rat plasma and its application in pharmacokinetic studies. AB - A highly sensitive and simple high-performance liquid chromatographic-tandem mass spectrometric (LC-MS-MS) assay is developed and validated for the quantification of sulforaphane and its metabolites in rat plasma. Sulforaphane (SFN) and its metabolites, sulforaphane glutathione (SFN-GSH) and sulforaphane N-acetyl cysteine (SFN-NAC) conjugates, are extracted from rat plasma by methanol-formic acid (100:0.1, v/v) and analyzed using a reversed-phase gradient elution on a Develosil 3 MUm RP-Aqueous C(30) 140A column. A 15-min linear gradient with acetonitrile-water (5:95, v/v), containing 10 mM ammonium acetate and 0.2% formic acid, as mobile phase A, and acetonitrile-water (95:5, v/v), containing 10 mM ammonium acetate and 0.2% formic acid as mobile phase B, is used. Sulforaphane and its metabolites are well separated. Sulforaphene is used as the internal standard. The lower limits of quantification are 1 ng/mL for SFN and 10 ng/mL for both SFN-NAC and SFN-GSH. The calibration curves are linear over the concentration range of 25-20,000 ng/mL of plasma for each analyte. This novel LC MS-MS method shows satisfactory accuracy and precision and is sufficiently sensitive for the performance of pharmacokinetic studies in rats. PMID- 22080810 TI - Effects of E-BEAM sterilization on drug-eluting stents: paclitaxel degradation elucidated by LC-MS-MS with information-dependent acquisition. AB - Effects of sterilization by electron beam (E-BEAM) on paclitaxel (1) mixed with poly(DL-lactide-co-glycolide) (PLG) in reservoirs of COSTAR Stents are examined by using liquid chromatography-mass spectrometry (LC-MS-MS) techniques with information-dependent acquisition (IDA). Numerous degradation products of 1 are formed in a beta-radiation dose-dependent manner to give plethora of low-level degradants. This behavior, together with multiple interferences from PLG-related compounds, creates considerable challenges for analysis of the drug/PLG mixtures. IDA methods with different survey scans are proven to be very efficient in elucidating degradation pathways and in identifying numerous products. Combined LC-MS-MS results from analysis of sterilized drug substance and stents indicate that water addition and oxidative processes together with the isomerization are largely responsible for degradation of 1 under E-BEAM sterilization conditions used. PMID- 22080811 TI - Determination of acrylamide in starch-based foods by HPLC with pre-column ultraviolet derivatization. AB - A new method is developed for the determination of acrylamide in starch-based foods. The method included the extraction of acrylamide with water, defatting with hexane, derivatization with potassium bromate (KBrO(3)) and potassium bromide (KBr), liquid-liquid extraction with ethyl acetate-hexane (4:1), and concentration. The final analyte (2-bromopropenamide, 2-BPA) is analyzed by high performance liquid chromatography coupled with diode array detection for quantification and by gas chromatography coupled to mass spectrometry for confirmation. The chromatographic analysis is performed on an ODS-3 C(18) column, and good retention and peak response of acrylamide are achieved under the optimal conditions. The limit of detection and quantitation are estimated to be 15 and 50 MUg/kg, respectively. The recoveries of acrylamide from the commercial samples are spiked at levels of 50-1000 MUg/kg, and range between 89.6 and 102.0%. These results show that this method should be regarded as a new, low-cost, and robust alternative for conventional investigation of acrylamide. PMID- 22080812 TI - Regeneration of tetrabutylammonium ion-pairing reagent distribution in a gradient elution of reversed phase ion-pair chromatography. AB - The regeneration of ion-pairing reagent distribution on liquid chromatography columns after gradient elution has been well recognized as the cause for long column equilibration time, a major drawback associated with gradient elution reverse phase ion-pair chromatography. To date, the majority of studies have focused on optimizing the separation conditions to shorten the equilibration time. There is limited understanding of the ion-pairing reagent distribution process between the mobile phase and stationary phase in the course of gradient elution, and subsequent column re-equilibration. The focus of this work is to gain a better understanding of this process. An ion-pair chromatographic system, equipped with a YMC ODS C(18) column and a mobile phase containing tetrabutylammonium (TBA) hydroxide as the ion-pairing reagent, was used in the study. The TBA distribution profile was established by measuring its concentration in the eluent fractions collected during the gradient cycle using different column equilibration times with an ion chromatographic method. Furthermore, the analyte retention time was evaluated as the function of the column equilibration time and TBA concentration in the mobile phase. The column equilibration and its impact on the method robustness will also be discussed. PMID- 22080813 TI - Intracellular drug delivery in Leishmania-infected macrophages: Evaluation of saponin-loaded PLGA nanoparticles. AB - Drug delivery systems present an opportunity to potentiate the therapeutic effect of antileishmanial drugs. Colloidal carriers are rapidly cleared by the phagocytic cells of the reticuloendothelial system (RES), rendering them ideal vehicles for passive targeting of antileishmanials. This paper describes the development of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for the antileishmanial saponin beta-aescin. NPs were prepared using the combined emulsification solvent evaporation/salting-out technique. Confocal microscopy was used to visualise the internalisation and intracellular trafficking of fluorescein- and nile red-labelled PLGA NPs in J774A.1 macrophages infected with GFP-transfected Leishmania donovani. The in vitro activity of aescin and aescin loaded NPs on L. infantum was determined in the axenic model as well as in the ex vivo model. The developed PLGA NPs were monodispersed with Z(ave)<300 nm, exhibited negative zeta potentials and had relatively high drug loadings ranging from 5.80 to 8.68% w/w PLGA. The fluorescent NPs were internalised by the macrophages and trafficked towards the lysosomes after 2 h in vitro incubation. Co-localisation of the NPs and the parasite was not shown. A two-fold increase in activity was observed in the ex vivo macrophage model by encapsulating beta aescin in PLGA NPs (IC(50), 0.48-0.76 ug/mL vs. 1.55 +/- 0.32 ug/mL for the free drug). PMID- 22080814 TI - Welfare regimes, population health and health inequalities: a research synthesis. AB - BACKGROUND: Research on the social determinants of health is increasingly using welfare regime theory. Although a key argument is that population health will be better and health inequalities lower in social democratic regimes than in others, this research has not been subjected to a systematic review. This paper identifies and assesses empirical studies that explicitly use a welfare regime typology in comparative health research. METHODS: 15 electronic databases and relevant bibliographies were searched to identify empirical studies published in English-language journals from January 1970 to February 2011. Thirty-three studies appearing in 14 peer-reviewed journals between 1994 and 2011 met the inclusion criteria. RESULTS: Three welfare regime typologies and their variants dominated existing work, which consisted of two broad study types: One compared population health and health inequalities across welfare regimes; the other considered relationships between health and the political determinants and policies of welfare regimes. Studies were further distinguished by the presence or absence of statistical significance testing of relationships of interest. Just under one half of studies comparing outcomes by regime found at least some evidence that health inequalities were lowest or population health was the best in social democratic countries. Studies analysing the relationship between health (mortality) and the political determinants or policies of welfare states were more likely to report results consistent with welfare regime theory. CONCLUSIONS: Health differences by regime were not always consistent with welfare regime theory. Measurement of policy instruments or outcomes of welfare regimes may be more promising for public health research than the use of typologies alone. PMID- 22080815 TI - Cumulative exposure to poor housing affordability and its association with mental health in men and women. AB - BACKGROUND: Poor housing affordability affects around 10% of the Australian population and is increasingly prevalent. The authors tested two hypotheses: that cumulative exposure to housing affordability stress (HAS) is associated with poorer mental health and that effects vary by gender. METHODS: The authors estimated the relationship between cumulative exposure to HAS and mental health among 15478 participants in an Australian longitudinal survey between 2001 and 2009. Individuals were classified as being in HAS if household income was in the lowest 40% of the national distribution and housing costs exceeded 30% of income. Exposure to HAS ranged from 1 to 8 annual waves. Mental health was measured using the Short Form 36 Mental Component Summary (MCS) score. To test the extent to which any observed associations were explained by compositional factors, random- and fixed-effects models were estimated. RESULTS: In the random-effects models, mental health scores decreased with increasing cumulative exposure to HAS (up until 4+ years). This relationship differed by gender, with a stronger dose response observed among men. The mean MCS score of men experiencing four to eight waves of housing stress was 2.02 points lower than men not in HAS (95% CI -3.89 to -0.16). In the fixed-effects models, there was no evidence of a cumulative effect of HAS on mental health; however, lower MCS was observed after a single year in HAS (beta=-0.70, 95% CI -1.02 to -0.37). CONCLUSIONS: While average mental health was lower for individuals with longer exposure to HAS, the mental health effect appears to be due to compositional factors. Furthermore, men and women appear to experience cumulative HAS differently. PMID- 22080817 TI - Understanding the link between environmental exposures and health: does the exposome promise too much? AB - Environmental exposures affecting human health range from complex mixtures, such as environmental tobacco smoke, ambient particulate matter air pollution and chlorination by products in drinking water, to hazardous chemicals, such as lead, and polycyclic aromatic hydrocarbons, such as benz(a)pyrene. The exposome has been proposed to complement the genome and be the totality of all environmental exposures of an individual over his or her lifetime. However, if measurements of the exposome in biological samples are the sole tool for exposure assessment there are a number of limitations. First, it has limited utility for fully capturing the impact of complex mixtures such environmental tobacco smoke or particulate matter air pollution. Second, a number of relevant environmental exposures such as noise, heat or electromagnetic fields do not have direct correlates as metabolites or protein adducts, but there is important evidence linking them with health effects. Third, functional genomic changes are likely in many instances to be both a susceptibility factor and a marker of internal doses in response to environmental exposures. Fourth, internal dose measurements of environmental exposures might have lost the distinct signature of the relevant sources. This paper emphasises the obligation of environmental epidemiology to provide robust evidence to assist timely and sufficient protection of vulnerable subgroups of populations from environmental hazards. Therefore, in applying the exposome concept to environmental health problems, a strong link with the external environment needs to be maintained. PMID- 22080816 TI - Current and long-term spousal caregiving and onset of cardiovascular disease. AB - BACKGROUND: Prior evidence suggests that caregiving may increase risk of cardiovascular disease (CVD) onset. This association has never been examined in a nationally (USA) representative sample, and prior studies could not fully control for socioeconomic confounders. This paper seeks to estimate the association between spousal caregiving and incident CVD in older Americans. METHODS: Married, CVD-free Health and Retirement Study respondents aged 50+ years (n=8472) were followed up to 8 years (1669 new stroke or heart disease diagnoses). Current caregiving exposure was defined as assisting a spouse with basic or instrumental activities of daily living >=14 h/week according to the care recipients' report in the most recent prior biennial survey; we define providing >=14 h/week of care at two consecutive biennial surveys as 'long-term caregiving'. Inverse probability weighted discrete-time hazard models with time-updated exposure and covariate information (including socioeconomic and cardiovascular risk factors) were used to estimate the effect of caregiving on incident CVD. RESULTS: Caregiving significantly predicted CVD incidence (HR=1.35, 95% CI 1.06 to 1.68) in the population overall. Long-term caregiving was associated with double the risk of CVD onset (HR=1.95, 95% CI 1.19 to 3.18). This association for long-term care givers varied significantly by race (p<0.01): caregiving predicted CVD onset for white (HR=2.37, 95% CI 1.43 to 3.92) but not for non-white (HR=0.28, 95% CI 0.06 to 1.28). CONCLUSIONS: Spousal caregiving independently predicted risk of CVD in a large sample of US adults. There was significant evidence that the effect for long-term care givers differs for non-whites and white. PMID- 22080818 TI - The Baby-Friendly Hospital Initiative shows positive effects on breastfeeding indicators in Brazil. AB - BACKGROUND: The Baby-Friendly Hospital Initiative (BFHI) has been implemented by WHO and Unicef with a view to protect, promote and support breast feeding. This paper aims to assess the influence of the BFHI on breastfeeding indicators in Brazil, using data from the 2nd Survey of Breastfeeding Prevalence, conducted in 2008. METHODS: Data on 64 municipalities were analysed: a total of 65,936 infants under the age of 1 year who were covered by the 2008 immunisation campaign. The outcomes of interest were breast feeding in the first hour of life in infants under 1 year of age; exclusive breast feeding on the first day after hospital discharge in infants under 4 months of age; exclusive breast feeding in infants under 2, 3 and 6 months of age; and pacifier use in infants under 6 months of age. The influence of birth in baby-friendly hospitals (BFHs) on these end points was analysed by means of Poisson regression with robust variance for complex samples. FINDINGS: Infants born in BFHs were 9% more likely to be breast fed in the first hour of life and 6% more likely to be breast fed on the first day at home. Exclusive breast feeding was 13%, 8% and 6% more likely in infants under the ages of 2, 3 and 6 months, respectively, born in BFHs. Birth in a BFH also correlated with significant less pacifier use. CONCLUSIONS: The BFHI has had an impact on several indicators of breast feeding. The authors hope the results of this study will make policy makers and health professionals aware of the importance and potential of this strategy. PMID- 22080819 TI - Age- and sex-specific reference limits for creatinine, cystatin C and the estimated glomerular filtration rate. AB - BACKGROUND: Early detection of patients with chronic kidney disease is of great importance. This study developed reference limits for serum creatinine and serum cystatin C concentrations and for the estimated glomerular filtration rate (eGFR) in healthy subjects from the general population aged 25-65 years. METHODS: This study defined a reference population including 985 subjects from the first follow up of the Study of Health in Pomerania. Serum creatinine was measured with a modified kinetic Jaffe method. Serum cystatin C was measured with a nephelometric assay. The eGFR was calculated from serum creatinine according to the Cockcroft Gault (eGFR(CG)) and the Modification of Diet in Renal Disease (eGFR(MDRD)) equation, respectively, as well as from serum cystatin C according to the formula by Larsson (eGFR(Larsson)). Non-parametric quantile regression was used to estimate the reference limits. For serum creatinine and serum cystatin C the 95th percentile and for eGFR(CG), eGFR(MDRD) and eGFR(Larsson) the 5th percentile were selected as reference limits. All data was weighted to reflect the age- and sex structure of the German population in 2008. RESULTS: The reference limits for serum creatinine (men: 1.11-1.23 mg/dL; women: 0.93-1.00 mg/dL) and serum cystatin C levels (men: 0.92-1.04 mg/L; women: 0.84-1.02 mg/L) increased with advancing age. The reference limits for eGFR decreased with increasing age (eGFR(CG) men: 106.0-64.7 mL/min, women 84.4-57.9 mL/min; eGFR(MDRD) men: 82.5 62.2 mL/min/1.73 m2, women 75.0-58.2 mL/min/1.73 m2; eGFR(Larsson) men: 85.5-72.9 mL/min, women 94.5-75.7 mL/min). CONCLUSIONS: This study presents age- and sex specific reference limits for five measures of renal function based on quantile regression models. PMID- 22080821 TI - A comparison of the acute effects of calcium and strontium ranelate on the serum marker of bone resorption. AB - BACKGROUND: To investigate the mechanism by which strontium ranelate (SrR) inhibits the bone resorption, this study compared the effects of SrR and calcium on parathyroid hormone (PTH) and the biochemical marker of bone resorption (serum type 1 collagen cross-linked C-telopeptide, betaCTX). METHODS: In 10 healthy young subjects, after overnight fasting, 1000 mg of elemental calcium and 2000 mg of SrR containing 600 mg Sr2+ were administered consecutively with a 1 week washout period. During the control period no drug was given. Fasting blood samples were drawn at baseline and throughout the next 5-h period. RESULTS: After the ingestion of either calcium or SrR, there was a significant increase in serum calcium and strontium concentrations, and a decrease in serum betaCTX and intact PTH concentrations as compared to the baseline values (p<0.05). In the fasting subjects, no significant differences in the variable were found as compared to the baseline values. CONCLUSIONS: The decrease in PTH and the marker of bone resorption observed after the SrR administration is comparable to the decrease observed after the calcium administration in young adults. PMID- 22080822 TI - Comparison of Bio-Plex measurements with standard techniques. PMID- 22080823 TI - Gastrointestinal infection as a trigger for inflammatory bowel disease. AB - PURPOSE OF REVIEW: There is accumulating evidence on the importance of microbes in the development and maintenance of both the intestinal and immune systems. This review focuses on the current findings on the role of gastrointestinal pathogens in the cause of chronic inflammatory bowel disease. RECENT FINDINGS: A number of intestinal pathogens including Mycobacterium avium subspecies paratuberculosis, adherent-invasive Escherichia coli, and Campylobacter species are associated at fairly high prevalence with Crohn's disease, while two recent studies found a low prevalence for cytomegalovirus. In a prospective study, M. avium subspecies paratuberculosis detection in early Crohn's disease was low and comparable to controls, while much higher in an established inflammatory bowel disease cohort. In the pediatric setting, a high prevalence of Clostridium difficile was seen in both active and inactive Crohn's disease and ulcerative colitis patients. Some studies have speculated that Salmonella or Campylobacter infection may increase the risk of inflammatory bowel disease on long-term follow up, but detection bias was found to obscure the risk. Recent studies in mouse models have demonstrated that a combination of factors, including viral pathogens, genetic susceptibility, and commensal microflora, can lead to intestinal pathology. SUMMARY: No evidence for causation of inflammatory bowel disease by a single agent has been found, whereas a number of microbes have been strongly associated with the presence of disease. The majority of recent studies support a role for the ability of intestinal pathogens to promote chronic inflammation in individuals with genetic susceptibility and/or other environmental factors which remain to be identified. These factors may include subsets of commensal microflora. PMID- 22080824 TI - Vaccines for enteric infections. AB - PURPOSE OF REVIEW: To provide a review of currently licensed enteric vaccines and their efficacy based on completed field trials. RECENT FINDINGS: In this review, we provide a brief description of the epidemiology of the most common enteric infections, in both developing and industrialized countries. We also describe the types, dosage, age-eligibility, availability, and efficacies of currently licensed vaccines, and review the results of recently completed clinical trials around the world. SUMMARY: Several enteric vaccines are currently available. Although some vaccines have proven highly effective in industrialized countries where the disease burden is low (so-called travelers vaccines), they have demonstrated a lower protective effect in endemic countries where the disease is more prevalent. However, due to the magnitude of disease in endemic countries, even with lower efficacy, the potential for a vaccine to reduce the absolute number of cases remains considerable. Despite the continued reduction in overall disease burden with increased public health measures, such as improved sanitation, antimicrobials, and greater public awareness, enteric infections continue to cause significant morbidity and mortality in vulnerable populations. We contend that adoption and dissemination of available vaccines at affordable prices should be accelerated, particularly in areas where the disease burden is highest. PMID- 22080825 TI - Approach to the patient with infectious colitis. AB - PURPOSE OF REVIEW: To provide current recommendations for evaluation and treatment of patients with infectious colitis. Infectious colitis is diagnosed in someone with diarrhea and one or more of the following: fever and/or dysentery, stools containing inflammatory markers such as leukocytes, lactoferrin, or calprotectin, or positive stool culture for an invasive or inflammatory bacterial enteropathogen including Shigella, Salmonella, Campylobacter, Shiga toxin producing Escherichia coli (STEC) or Clostridium difficile, or colonic inflammation by endoscopy. RECENT FINDINGS: Standard stool culture should be performed in patients with infectious colitis. Epidemiologic findings including prior international travel, shellfish-associated diarrhea, living in parasite endemic regions may suggest the need for specialized studies of etiology. When STEC is suspected as a pathogen because only low grade or no fever is seen in a patient with acute dysentery, a competent laboratory should look for E. coli O157:H7 and Shiga toxin directly in stool. SUMMARY: Once laboratory diagnosis is made, pathogen-specific antimicrobial therapy should be initiated for all forms of infectious colitis other than STEC. For empiric treatment of febrile dysenteric diarrhea invasive bacterial enteropathogens (Shigella, Salmonella, and Campylobacter) should be suspected and adults may be treated empirically with 1000mg azithromycin in a single dose. PMID- 22080826 TI - Motility disorders of the colon and rectum. AB - PURPOSE OF REVIEW: The major motor functions of the large bowel include storage, propulsion and defecation. New developments continue to expand our knowledge of this area and provide significant advances in the treatment of disorders of colorectal motility. RECENT FINDINGS: This article reviews new techniques to study colon motility and transit in health and constipation, recent published data which support the efficacy of novel and established laxatives for both functional and opioid-induced constipation, the development of neuromodulatory techniques for severe constipation and new insights into the pathogenesis and treatment of levator syndrome. SUMMARY: The articles referenced in this review inform the reader of new developments in understanding and treating disorders of colonic and anorectal motility and anticipate future advances. PMID- 22080827 TI - The intestinal microbiota in health and disease. AB - PURPOSE OF REVIEW: The indigenous gut microbiota has been shown to be a key player in maintaining gastrointestinal homeostasis. This review discusses some of the recent work that reveals how the gut microbiome helps establish and protect intestinal health and how disturbances in this microbial community can lead to disease states. RECENT FINDINGS: The use of culture-independent methods has greatly improved our ability to determine the structure and function of the gut microbiome. The gut microbiota has critical interactions with the host immune system and metabolism with bilateral influences shaping both the host and the microbiome. Alterations in the gut microbiome are associated with a variety of disease states but we are only now beginning to understand the mechanisms by which this occurs. SUMMARY: Understanding how the gut microbiome contributes to intestinal health should lead to novel preventive strategies and therapies for a variety of gastrointestinal conditions. PMID- 22080828 TI - An investigation of inconsistent projections and artefacts in multi-pinhole SPECT with axially aligned pinholes. AB - Multiple pinholes are advantageous for maximizing the use of the available field of view (FOV) of compact small animal single photon emission computed tomography (SPECT) detectors. However, when the pinholes are aligned axially to optimize imaging of extended objects, such as rodents, multiplexing of the pinhole projections can give rise to inconsistent data which leads to 'ghost point' artefacts in the reconstructed volume. A novel four pinhole collimator with a baffle was designed and implemented to eliminate these inconsistent projections. Simulation and physical phantom studies were performed to investigate artefacts from axially aligned pinholes and the efficacy of the baffle in removing inconsistent data and, thus, reducing reconstruction artefacts. SPECT was performed using a Defrise phantom to investigate the impact of collimator design on FOV utilization and axial blurring effects. Multiple pinhole SPECT acquired with a baffle had fewer artefacts and improved quantitative accuracy when compared to SPECT acquired without a baffle. The use of four pinholes positioned in a square maximized the available FOV, increased acquisition sensitivity and reduced axial blurring effects. These findings support the use of a baffle to eliminate inconsistent projection data arising from axially aligned pinholes and improve small animal SPECT reconstructions. PMID- 22080829 TI - Retraction. Mitochondrial pathophysiology and type 2 diabetes mellitus. PMID- 22080830 TI - Validation of the key informant method to identify children with disabilities: methods and results from a pilot study in Bangladesh. AB - PURPOSE: To assess whether the key informant method (KIM) is an effective method to identify children with disabling sensory or physical impairments, or epilepsy (tonic-clonic seizures), in a low-income setting. METHODS: In one subdistrict each, the Key Informants (KIs) were trained to recognize children with visual impairment, hearing impairment, physical impairment and epilepsy, respectively. In the fifth subdistrict, the KIs were trained to recognize all four conditions. RESULTS: Of the 2260 children identified by KIs, 1227 attended for examination (54%), of which 911 were diagnosed to have a disabling impairment (74%). KIM had a high sensitivity (average 98%) for case detection in all groups but specificity was lower (average 44%), particularly for hearing impairment. CONCLUSIONS: KIs were able to identify children with epilepsy, sensory and physical impairments. KIM is an effective and low-cost method to identify children with disability in a low-income setting. PMID- 22080831 TI - Ethanol increases GABAergic transmission and excitability in cerebellar molecular layer interneurons from GAD67-GFP knock-in mice. AB - AIMS: This study assessed the acute effect of ethanol on GABAergic transmission at molecular layer interneurons (MLIs; i.e. basket and stellate cells) in the cerebellar cortex. The actions of ethanol on spontaneous firing of these pacemaker neurons were also measured. METHODS: Transgenic mice (glutamic acid decarboxylase 67-green fluorescent protein knock-in mice) that express green fluorescence protein in GABAergic interneurons were used to aid in the identification of MLIs. Parasagittal cerebellar slices were prepared and whole cell patch-clamp electrophysiological techniques were used to measure GABA(A) receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs). Loose-seal cell-attached recordings were used to measure spontaneous action potential firing. RESULTS: Stellate cells received spontaneous GABAergic input in the form of a mixture of action potential-dependent events (sIPSCs) and quantal events (mIPSCs); ethanol increased sIPSC frequency to a greater extent than mIPSC frequency. Ethanol increased spontaneous action potential firing of MLIs, which could explain the increase in sIPSC frequency in stellate cells. Basket cells received GABAergic input in the form of quantal events only. Ethanol significantly increased the frequency of these events, which may be mediated by a different type of interneuron (perhaps, the Lugaro cell) or Purkinje cell collaterals. CONCLUSIONS: Ethanol exposure differentially increases GABA release at stellate cell vs. basket cell-to-Purkinje cell synapses. This effect may contribute to the abnormalities in cerebellar function associated with alcohol intoxication. PMID- 22080832 TI - HLA class I sensitization in islet transplant recipients: report from the Collaborative Islet Transplant Registry. AB - Pancreatic islet transplantation is a promising treatment option for patients severely affected with type 1 diabetes. This report from CITR presents pre- and posttransplant human leukocyte antigen (HLA) class I sensitization rates in islet alone transplantation. Data came from 303 recipients transplanted with islet alone between January 1999 and December 2008. HLA class I sensitization was determined by the presence of anti-HLA class I antibodies. Panel-reactive antibodies (PRA) from prior to islet infusion and at 6 months, and yearly posttransplant was correlated to measures of islet graft failure. The cumulative number of mismatched HLA alleles increased with each additional islet infusion from a median of 3 for one infusion to 9 for three infusions. Pretransplant PRA was not predictive of islet graft failure. However, development of PRA >20% posttransplant was associated with 3.6-fold (p < 0.001) increased hazard ratio for graft failure. Patients with complete graft loss who had discontinued immunosuppression had significantly higher rate of PRA >= 20% compared to those with functioning grafts who remained on immunosuppression. Exposure to repeat HLA class I mismatch at second or third islet infusions resulted in less frequent development of de novo HLA class I antibodies when compared to increased class I mismatch. The development of HLA class I antibodies while on immunosuppression is associated with subsequent islet graft failure. The risk of sensitization may be reduced by minimizing the number of islet donors used per recipient, and in the absence of donor-specific anti-HLA antibodies, repeating HLA class I mismatches with subsequent islet infusions. PMID- 22080833 TI - Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus dystonia mouse models. AB - DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for epsilon-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of epsilon-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of epsilon-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of epsilon-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID- 22080834 TI - Knockdown of the psychosis susceptibility gene ZNF804A alters expression of genes involved in cell adhesion. AB - Genome-wide association studies have convincingly implicated several novel genes in susceptibility to schizophrenia and bipolar disorder. The first genome-wide significant association with the broad phenotype of psychosis was with a polymorphism in the ZNF804A gene. However, the biological function(s) of ZNF804A have, to date, been entirely unknown. In this study, we manipulated the expression of ZNF804A in neural progenitor cells derived from human cortical neuroepithelium and assessed its effects on the cellular transcriptome. Gene ontology analysis of differentially expressed genes indicated a significant effect of ZNF804A knockdown on the expression of genes involved in cell adhesion, suggesting a role for ZNF804A in processes such as neural migration, neurite outgrowth and synapse formation. Several highly significant gene expression changes were confirmed in repeat cell culture experiments. Most consistent gene expression changes were seen for C2ORF80, a gene of as-yet-unknown function, and STMN3, a gene involved in neurite outgrowth and axonal and dendritic branching. These data, generated in a hypothesis-free manner, provide a basis for more targeted investigations of ZNF804A function. PMID- 22080835 TI - Mitochondrial autophagy in cells with mtDNA mutations results from synergistic loss of transmembrane potential and mTORC1 inhibition. AB - Autophagy has emerged as a key cellular process for organellar quality control, yet this pathway apparently fails to eliminate mitochondria containing pathogenic mutations in mitochondrial DNA (mtDNA) in patients with a variety of human diseases. In order to explore how mtDNA-mediated mitochondrial dysfunction interacts with endogenous autophagic pathways, we examined autophagic status in a panel of human cytoplasmic hybrid (cybrid) cell lines carrying a variety of pathogenic mtDNA mutations. We found that both genetic- and chemically induced loss of mitochondrial transmembrane potential (Deltapsi(m)) caused recruitment of the pro-mitophagic factor Parkin to mitochondria. Strikingly, however, the loss of Deltapsi(m) alone was insufficient to prompt delivery of mitochondria to the autophagosome (mitophagy). We found that mitophagy could be induced following treatment with the mTORC1 inhibitor rapamycin in cybrids carrying either large scale partial deletions of mtDNA or complete depletion of mtDNA. Further, we found that the level of endogenous Parkin is a crucial determinant of mitophagy. These results suggest a two-hit model, in which the synergistic induction of both (i) mitochondrial recruitment of Parkin following the loss of Deltapsi(m) and (ii) mTORC1-controlled general macroautophagy is required for mitophagy. It appears that mitophagy can be accomplished by the endogenous autophagic machinery, but requires the full engagement of both of these pathways. PMID- 22080836 TI - In vivo neuronal function of the fragile X mental retardation protein is regulated by phosphorylation. AB - Fragile X syndrome (FXS), caused by loss of the Fragile X Mental Retardation 1 (FMR1) gene product (FMRP), is the most common heritable cause of intellectual disability and autism spectrum disorders. It has been long hypothesized that the phosphorylation of serine 500 (S500) in human FMRP controls its function as an RNA-binding translational repressor. To test this hypothesis in vivo, we employed neuronally targeted expression of three human FMR1 transgenes, including wild type (hFMR1), dephosphomimetic (S500A-hFMR1) and phosphomimetic (S500D-hFMR1), in the Drosophila FXS disease model to investigate phosphorylation requirements. At the molecular level, dfmr1 null mutants exhibit elevated brain protein levels due to loss of translational repressor activity. This defect is rescued for an individual target protein and across the population of brain proteins by the phosphomimetic, whereas the dephosphomimetic phenocopies the null condition. At the cellular level, dfmr1 null synapse architecture exhibits increased area, branching and bouton number. The phosphomimetic fully rescues these synaptogenesis defects, whereas the dephosphomimetic provides no rescue. The presence of Futsch-positive (microtubule-associated protein 1B) supernumerary microtubule loops is elevated in dfmr1 null synapses. The human phosphomimetic restores normal Futsch loops, whereas the dephosphomimetic provides no activity. At the behavioral level, dfmr1 null mutants exhibit strongly impaired olfactory associative learning. The human phosphomimetic targeted only to the brain learning center restores normal learning ability, whereas the dephosphomimetic provides absolutely no rescue. We conclude that human FMRP S500 phosphorylation is necessary for its in vivo function as a neuronal translational repressor and regulator of synaptic architecture, and for the manifestation of FMRP-dependent learning behavior. PMID- 22080837 TI - LRRK2 Parkinson disease mutations enhance its microtubule association. AB - Dominant missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic causes of Parkinson disease (PD) and genome-wide association studies identify LRRK2 sequence variants as risk factors for sporadic PD. Intact kinase function appears critical for the toxicity of LRRK2 PD mutants, yet our understanding of how LRRK2 causes neurodegeneration remains limited. We find that most LRRK2 PD mutants abnormally enhance LRRK2 oligomerization, causing it to form filamentous structures in transfections of cell lines or primary neuronal cultures. Strikingly, ultrastructural analyses, including immuno-electron microscopy and electron microscopic tomography, demonstrate that these filaments consist of LRRK2 recruited onto part of the cellular microtubule network in a well-ordered, periodic fashion. Like LRRK2-related neurodegeneration, microtubule association requires intact kinase function and the WD40 domain, potentially linking microtubule binding and neurodegeneration. Our observations identify a novel effect of LRRK2 PD mutations and highlight a potential role for microtubules in the pathogenesis of LRRK2-related neurodegeneration. PMID- 22080839 TI - Improving adherence--money isn't the only thing. PMID- 22080842 TI - Acupuncture and constitutional diagnosis: where now? PMID- 22080840 TI - Prenatal tetrahydrocannabinol (THC) alters cognitive function and amphetamine response from weaning to adulthood in the rat. AB - Research suggests that not only is marijuana use prevalent among women of reproductive age, but a significant number of women continue to use marijuana and its derivatives throughout pregnancy. Many studies have shown, in both humans and animals, that marijuana exposure during adolescence and adulthood is detrimental to normal cognition and memory. In this study, we examined the effects of daily intravenous injections of 0.15 mg/kg Delta(9)-tetrahydrocannabinol (THC), given to pregnant dams throughout gestation, on cognitive function in the offspring. Offspring were exposed to three tests: a passive avoidance test at postnatal day (PND) 22, an active place avoidance test at PND 45, and an attention task at PND 60, which assessed learning and long-term memory, spatial working memory and prediction, and attention, respectively. Other offspring were also given a 1mg/kg amphetamine challenge at PND 60. Passive avoidance testing showed that prenatal THC had no effect on acquisition but interfered with consolidation during retention testing. The active place avoidance task showed no treatment-related effects on acquisition but a significant treatment effect was observed in reversal performance in males. The attention task showed that a smaller percentage of THC-exposed rats completed the test, although the failure rate of both groups was quite high. Finally, THC exposed animals, both male and female, showed a dampened locomotor response to amphetamine, but females were more active than males overall. These results suggest that prenatal THC exposure has effects on certain aspects of cognitive function in rats from weaning to adulthood. These effects suggest that prenatal marijuana exposure could also alter cognitive function in humans and therefore have an impact on school performance and dampen responses to psychostimulants as well. PMID- 22080843 TI - Porous organic cage nanocrystals by solution mixing. AB - We present here a simple method for the bottom-up fabrication of microporous organic particles with surface areas in the range 500-1000 m(2) g(-1). The method involves chiral recognition between prefabricated, intrinsically porous organic cage molecules that precipitate spontaneously upon mixing in solution. Fine control over particle size from 50 nm to 1 MUm can be achieved by varying the mixing temperature or the rate of mixing. No surfactants or templates are required, and the resulting organic dispersions are stable for months. In this method, the covalent synthesis of the cage modules can be separated from their solution processing into particles because the modules can be dissolved in common solvents. This allows a "mix and match" approach to porous organic particles. The marked solubility change that occurs upon mixing cages with opposite chirality is rationalized by density functional theory calculations that suggest favorable intermolecular interactions for heterochiral cage pairings. The important contribution of molecular disorder to porosity and surface area is highlighted. In one case, a purposefully amorphized sample has more than twice the surface area of its crystalline analogue. PMID- 22080844 TI - Estimation of phytochemicals and antioxidant activity of underutilized fruits of Andaman Islands (India). AB - The present study aimed to determine the antioxidant activity and phytochemical contents in 10 underutilized fruits of Andaman Islands (India) namely Malpighia glabra L., Mangifera andamanica L., Morinda citrifolia L., Syzygium aqueum (Burm.f) Alst., Annona squamosa L., Averrhoa carambola L., Averrhoa bilimbi L., Dillenia indica L., Annona muricata L. and Ficus racemosa L. The antioxidant activity varied from 74.27% to 98.77%, and the methanol extract of M. glabra showed the highest antioxidant activity (98.77%; inhibitory concentration, IC(50) = 262.46 MUg/ml). Methanol was found to be a better solvent than acetone and aqueous for estimating the antioxidant activity. M. glabra was found to be rich in phytochemicals viz. polyphenol (355.74 mg/100 g), anthocyanin (91.31 mg/100 g), carotenoids (109.16 mg/100 g), tannin (24.39 mg/100 g) and ascorbic acid (394.23 mg/100 g). Carbohydrate content was estimated to be highest in M. glabra (548 mg/100 g). Phenols, tannins, anthocyanins and carotenoids contents showed positive correlation (r2 = 0.846, r2 = 0.864, r2 = 0.915 and r2 = 0.806, respectively) with antioxidant activity. The information generated in present study will be useful for bioprospecting of underutilized fruits of Andaman Islands. PMID- 22080846 TI - Neutropenia after rituximab treatment: new insights on a late complication. AB - PURPOSE OF REVIEW: Late-onset neutropenia (LON) after rituximab administration may be encountered in various clinical settings. The identification of neutropenia after rituximab treatment may have immediate implications for the clinical management of the patient and on subsequent treatment strategies. Although the pathogenesis of LON is incompletely understood, various putative mechanisms are suggested. These may be of special importance in the advent of the newer monoclonal anti-CD20 antibodies. RECENT FINDINGS: The incidence of LON varies with the clinical setting in which rituximab is administered. Administration of rituximab in the setting of stem cell transplantation significantly increases the risk for LON. The timing of rituximab administration after transplantation may affect the risk and severity of neutropenia. Recent data suggest that in rheumatologic diseases, the incidence of LON is comparable to that in the hematologic population. Suggested mechanisms for LON include humoral and cellular immune mechanisms as well processes that stem from B-cell recovery and its impact on neutrophil kinetics. Recently, an association between specific polymorphism in the immunoglobulin G Fc receptor FCgammaRIIIa 158 V/F and LON was demonstrated. SUMMARY: LON is an increasingly recognized late adverse event of rituximab therapy. Acquaintance with the incidence, risk factors, natural history, and expected complications of LON may improve proper clinical management. Many aspects in the clinical management of LON remain to be answered during further studies aimed at this goal. PMID- 22080845 TI - Hematopoietic stem cell transplantation for severe congenital neutropenia. AB - PURPOSE OF REVIEW: Hematopoietic stem cell transplantation (HCT) is the only curative option for patients with severe congenital neutropenia (SCN). Transplant success is dependent on identifying at-risk patients and proceeding to transplant before the development of severe infections or malignant transformation. This review focuses on recent advancements in risk stratification of SCN patients, indications for HCT, and review of published transplant studies. RECENT FINDINGS: Patients with poor neutrophil response despite high doses of granulocyte colony stimulating factor (G-CSF) are at greatest risk for malignant transformation. Other studies demonstrate elevated risk with mutations in the G-CSF receptor gene and a specific mutation in the ELANE gene. These patients are at high-risk of sepsis or leukemia development and should proceed to transplant with best available donor. As recent published studies demonstrate, HCT is highly successful in patients without leukemia and, therefore, may be considered in selected low-risk patients given the life-long risk of malignancy and infection. SUMMARY: The decision whether to proceed to HCT in healthy patients maintained on G-CSF is difficult. As transplant-related mortality continues to decrease, the role of transplant in SCN is likely to expand to more patients. PMID- 22080838 TI - A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. AB - The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 * 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior. PMID- 22080847 TI - Use of antibacterial prophylaxis in patients with chemotherapy-induced neutropenia. AB - PURPOSE OF REVIEW: Antibiotic prophylaxis has been found to have multiple benefits in patients receiving intensive chemotherapy at high risk for infection. Interest continues in identifying what additional groups of high-risk patients might potentially benefit from its use. However, concerns about the potential emergence of antibiotic resistance have led to multiple recent studies exploring this issue. RECENT FINDINGS: The use of antibiotic prophylaxis in pediatric leukemia, myelodysplastic syndromes, and hematopoietic stem cell transplant populations has been evaluated in recent studies. Several centers have noted increased rates of antibiotic resistance in patients receiving prophylaxis. SUMMARY: Several single-center studies have emphasized the concern for the emergence of antibiotic resistance associated with the routine use of fluoroquinolone prophylaxis. The potential for antibiotic resistance continues to be worrisome and warrants further ongoing studies. PMID- 22080848 TI - Update on anemia and neutropenia in copper deficiency. AB - PURPOSE OF REVIEW: Copper deficiency is an under-recognized cause of reversible refractory anemia and leukopenia, particularly neutropenia, often misdiagnosed as myelodysplastic syndrome (MDS). Clinicians and hematopathologists need to be aware of distinct morphologic findings to distinguish these entities including cytoplasmic vacuolization of both erythroid and myeloid precursors, excess iron stores, ringed sideroblasts, iron incorporation in plasma cells, and variable marrow cellularity. In contrast, the findings in MDS do not include myeloid lineage vacuolization, abnormal nuclear lobulation of both erythroid and myeloid precursors, nuclear/cytoplasmic dyssynchrony, or dysmegakaryopoiesis with abnormalities of nuclear lobulation and size. RECENT FINDINGS: The mechanism of neutropenia remains unknown; however, the study by Peled and coworkers suggests that copper deficiency results in the inhibition of differentiation and self renewal of CD34(+) hematopoietic progenitor cells. A number of recent studies have reported on the association of copper deficiency with the development of concomitant neurologic deficits manifested as peripheral neuropathies and myeloneuropathy indistinguishable from the findings seen in vitamin B12 deficiency. SUMMARY: Patients presenting with refractory anemia and leukopenia with or without associated neurologic deficits should have copper and ceruloplasmin levels measured as part of their diagnostic evaluation. PMID- 22080850 TI - Biodiversity of avian trypanosomes. AB - We have studied the biodiversity of trypanosomes from birds and bloodsucking Diptera on a large number of isolates. We used two molecular approaches, random amplification of polymorphic DNA (RAPD) method, and sequence analysis of the small subunit ribosomal RNA (SSU rRNA) gene. RAPD method divided the isolates into 11 separate lineages. Phylogenetic analysis of the SSU rRNA gene was congruent with the RAPD. Morphometric analysis of kinetoplast width and cell length was in agreement with molecular data. Avian trypanosomes appeared polyphyletic on SSU rDNA tree; thus, they do not represent a taxonomic group. We propose that all lineages recovered by SSU analysis probably represent distinct species of avian trypanosomes. We discuss possible transmission ways and geographical distribution of new avian trypanosome lineages. Finally, we recommend methods that should be used for species determination of avian trypanosomes. PMID- 22080849 TI - Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. Data from a large prospective and retrospective Italian epidemiological study: the NET management study. AB - BACKGROUND: The few epidemiological data available in literature on neuroendocrine tumors (NET) are mainly based on Registry databases, missing therefore details on their clinical and natural history. AIM: To investigate epidemiology, clinical presentation, and natural history of NET. DESIGN AND SETTING: A large national retrospective survey was conducted in 13 Italian referral centers. Among 1203 NET, 820 originating in the thorax (T-NET), in the gastro-enteropancreatic tract (GEP-NET) or metastatic NET of unknown primary origin (U-NET) were enrolled in the study. RESULTS: 93% had a sporadic and 7% a multiple endocrine neoplasia type 1 (MEN1)-associated tumor; 63% were GEP-NET, 33% T-NET, 4% U-NET. Pancreas and lung were the commonest primary sites. Poorly differentiated carcinomas were <10%, all sporadic. The incidence of NET had a linear increase from 1990 to 2007 in all the centers. The mean age at diagnosis was 60.0 +/- 16.4 yr, significantly anticipated in MEN1 patients (47.7 +/- 16.5 yr). Association with cigarette smoking and other non-NET cancer were more prevalent than in the general Italian population. The first symptoms of the disease were related to tumor burden in 46%, endocrine syndrome in 23%, while the diagnosis was fortuity in 29%. Insulin (37%) and serotonin (35%) were the most common hormonal hypersecretions. An advanced tumor stage was found in 42%, more frequently in the gut and thymus. No differences in the overall survival was observed between T-NET and GEP-NET and between sporadic and MEN1-associated tumors at 10 yr from diagnosis, while survival probability was dramatically reduced in U-NET. CONCLUSIONS: The data obtained from this study furnish relevant information on epidemiology, natural history, and clinico-pathological features of NET, not available from the few published Register studies. PMID- 22080851 TI - Transcription profiles for two key gender-specific gene families in Oesophagostomum dentatum during development in vivo and in vitro. AB - In strongylid roundworms, such as Oesophagostomum dentatum (porcine nodule worm), some sex-specific genes are likely to be associated with parasite maturation, development and reproduction. In this study, an analysis of transcription of the two sex-specific genes (vit and msp) encoding vitellogenin and major sperm protein of O. dentatum, respectively, revealed that adult females transcribed vit and adult males msp at high levels, in contrast to immature larval stages and pre adult worms from in vitro cultures for which no transcription of vit or msp was detected. The analysis showed that neither presence nor absence of the heterologous sex, nor the duration of infection, was central to vit or msp transcription. In small or "virgin" adults, no or only low-level transcription of vit and msp was detectable. We hypothesize that the transcription of the sex specific genes is linked to endogenous factors, such as size, maturation of the reproductive organs and/or fitness of the worms, and not to exogenous influences. The maturation of worms appears to be linked, to some extent, to the expression of the genes studied herein. PMID- 22080852 TI - Multiplex RT-PCR assays for the simultaneous detection of both RNA and DNA viruses infecting cassava and the common occurrence of mixed infections by two cassava brown streak viruses in East Africa. AB - Uniplex and multiplex reverse transcription-polymerase chain reaction (RT-PCR) protocols were developed for the detection of cassava brown streak viruses (CBSVs) in single and mixed infections with cassava mosaic begomoviruses (CMBs) in a tropical crop plant, cassava (Manihot esculenta). CMBs contain ssDNA as their genome (genus Begomovirus, family Geminiviridae) while CBSVs are made up of positive sense ssRNA (genus Ipomovirus, family Potyviridae), and they cause the economically important cassava mosaic and cassava brown streak diseases, respectively, in sub-Saharan Africa. Diagnostic methodologies have long been available for CMBs but they are limited for CBSVs especially in mixed infections. In this study, the two CBSVs, Cassava brown streak virus (CBSV) and Cassava brown streak Uganda virus (CBSUV) occurring singly or in mixed infection with CMBs, African cassava mosaic virus and East African cassava mosaic virus were detected in a single RT-PCR using both previously described and newly designed virus specific primers. These protocols were highly efficient for detecting CBSVs compared to the existing methods and have great potential to minimize sample handling and contamination. As well as improving the diagnosis of cassava viruses, the development of multiplex RT-PCR protocols have revealed the common occurrence of mixed infections by CBSV and CBSUV in cassava fields of Tanzania and Kenya, which was contrary to the common belief until recently that these two viruses have existed separately. These protocols have implications for diagnosis and epidemiological studies on cassava virus diseases in Eastern Africa. PMID- 22080853 TI - Evaluation of ELISA for detection of rabies antibodies in domestic carnivores. AB - Serological tests of pets have increased as many rabies-free countries have amended their quarantine measures and adopted a scheme requiring rabies vaccination followed by a serological test. A European directive requires the measurement of neutralising antibodies as proof of protection to allow the free movement of pets within the European Union and between third countries non listed in the list C of regulation 998/2003 and European countries. At present, the recommended neutralisation tests (FAVN test or RFFIT) are time-consuming, expensive and require highly trained technicians as well as special laboratory facilities. The rabies ELISA designed by BioPro was developed initially for use for field samples from foxes to check the efficacy of oral vaccination campaigns in Europe. In this study, the specificity, sensitivity and reliability of this commercial rabies ELISA was evaluated for testing sera from dogs and cats involved in international trade. The specificity evaluated in 315 unvaccinated animals was 100%. Concordance of 86.2% was obtained when comparing BioPro ELISA to the gold standard FAVN test in 701 samples from vaccinated dogs and cats. The rabies ELISA developed recently can be considered a valuable method for the assessment of rabies antibodies in vaccinated domestic carnivores in combination with neutralisation tests. PMID- 22080854 TI - Systemic enhancement of papaverine transdermal gel for erectile dysfunction. AB - To enhance the systemic transdermal delivery of papaverine for the treatment of erectile dysfunction, several factors that influence transdermal delivery of papaverine HCl were studied. The effects of membrane types for in vitro permeation study, human skin layers, solvent/cosolvent systems and the penetration enhancers on the transdermal permeation of papaverine HCl were investigated. A combination of caproic acid, ethanol and water in the volume ratio of 50%:30%:20% was chosen as penetration enhancer and incorporated in two gel bases: 18% Pluronic F-127 and 2% Carbopol 940. In vivo skin permeation studies were performed with two loading doses (0.6% and 2%) in rabbits. The flux and permeability coefficient of papaverine HCl through different human skin layers suggested that the major barrier layer for papaverine HCl was residing primarily in the stratum corneum. However, the viable epidermis and dermis layer also contributed certain degrees of diffusion resistance. Differential Scanning Calorimetry study showed that penetration enhancer exhibited a counter effect with papaverine HCl on the temperature and enthalpy in both gels. In vitro drug release study demonstrated significant increases in the steady-state flux, permeability coefficient and enhancement ratio in these gels. Faster drug transports and higher bioavailability were also observed in rabbits. Skin irritation test performed in rabbits demonstrated a mild skin reaction with mean PII scores of 2 and below; however the recovery was fast. In conclusion, caproic acid, ethanol and water in the volume ratio of 50%:30%:20% is an effective penetration enhancer to deliver papaverine HCl transdermally for systemic absorption. PMID- 22080855 TI - Role of medullary blood flow in the pathogenesis of renal ischemia-reperfusion injury. AB - PURPOSE OF REVIEW: Renal ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI). Alterations in renal medullary blood flow (MBF) contribute to the pathogenesis of renal IRI. Here we review recent insights into the mechanisms of altered MBF in the pathogenesis of IRI. RECENT FINDINGS: Although cortical blood flow fully recovers following 30-45 min of bilateral IRI, recent studies have indicated that there is a prolonged secondary fall in MBF that is associated with a long-term decline in renal function. Recent findings indicate that angiopoietin-1, atrial natriuretic peptide, heme oxygenase 1, and the gasotransmitters CO and H(2)S, may limit the severity of IRI by preserving MBF. Additional studies have also suggested a role for cytochrome P450 derived 20-HETE in the postischemic fall in MBF. SUMMARY: Impaired MBF contributes to the pathogenesis of renal IRI. Measurement of renal MBF provides valuable insight into the underlying mechanisms of many renoprotective pathways. Identification of molecules that preserve renal MBF in IRI may lead to new therapies for AKI. PMID- 22080856 TI - Adenosine and protection from acute kidney injury. AB - PURPOSE OF REVIEW: Acute kidney injury (AKI) is a major clinical problem without effective therapy. Development of AKI among hospitalized patients drastically increases mortality and morbidity. With increases in complex surgical procedures together with a growing elderly population, the incidence of AKI is rising. Renal adenosine receptor manipulation may have great therapeutic potential in mitigating AKI. In this review, we discuss renal adenosine receptor biology and potential clinical therapies for AKI. RECENT FINDINGS: The four adenosine receptor subtypes (A(1)AR, A(2A)AR, A(2B)AR, and A(3)AR) have diverse effects on the kidney. The pathophysiology of AKI may dictate the specific adenosine receptor subtype activation needed to produce renal protection. The A(1)AR activation in renal tubules and endothelial cells produces beneficial effects against ischemia and reperfusion injury by modulating metabolic demand, decreasing necrosis, apoptosis, and inflammation. The A(2A)AR protects against AKI by modulating leukocyte-mediated renal and systemic inflammation, whereas the A(2B)AR activation protects by direct activation of renal parenchymal adenosine receptors. In contrast, the A(1)AR antagonism may play a protective role in nephrotoxic AKI and radiocontrast induced nephropathy by reversing vascular constriction and inducing naturesis and diuresis. Furthermore, as the A(3)AR activation exacerbates apoptosis and tissue damage due to renal ischemia and reperfusion, selective A(3)AR antagonism may hold promise to attenuate renal ischemia and reperfusion injury. Finally, renal A(1)AR activation also protects against renal endothelial dysfunction caused by hepatic ischemia and reperfusion injury. SUMMARY: Despite the current lack of therapies for the treatment and prevention of AKI, recent research suggests that modulation of renal adenosine receptors holds promise in treating AKI and extrarenal injury. PMID- 22080857 TI - Pathogenesis of pseudohypoaldosteronism type 2 by WNK1 mutations. AB - PURPOSE OF REVIEW: Pseudohypoaldosteronism type 2 (PHA2) is a rare autosomal dominant form of human arterial hypertension, associated with hyperkalemia and hyperchloremic metabolic acidosis. WNK1 and WNK4 are two of the genes mutated in PHA2 patients. This review focuses on the mechanisms by which deletions of the first intron of WNK1 found in PHA2 patients trigger the disease. RECENT FINDINGS: The WNK1 gene gives rise to a ubiquitous kinase (L-WNK1) and to a shorter kinase defective isoform, KS-WNK1 (for kidney-specific WNK1), expressed only in the distal convoluted tubule (DCT) and connecting tubule. WNK1 first intron deletion leads to overexpression of L-WNK1 in the DCT and ubiquitous ectopic expression of KS-WNK1. The increased expression of L-WNK1 in the DCT results in increased activity of the Na-Cl cotransporter (NCC) and thus hypervolemia and hypertension. Contrarily, the mechanisms underlying the hyperkalemia and metabolic acidosis remain unclear. SUMMARY: As particularly small doses of thiazide diuretics, inhibitors of NCC activity, correct both the blood pressure and metabolic disorders in PHA2 patients, it was believed that increased NCC was directly responsible for all PHA2 features. Studies performed in mouse models of KS-WNK1 inactivation or WNK4-related PHA2, however, have revealed that the situation is much more complex. PMID- 22080859 TI - Sympathetic nervous system: role in hypertension and in chronic kidney disease. AB - PURPOSE OF REVIEW: A number of cardiovascular disease have been shown to be characterized by a marked increase in sympathetic drive to the heart and peripheral circulation. This is the case for essential hypertension, congestive heart failure, obesity, metabolic syndrome and chronic renal failure. This review focuses on the most recent findings documenting the role of sympathetic neural factors in the development and progression of the hypertensive state as well as of target organ damage. It also reviews the participation of sympathetic neural factors in the development of the earlier stages of renal failure. RECENT FINDINGS: A marked increase in sympathetic neural discharge, as assessed via the microneurographic technique, has been shown to occur in the predialytic stage of chronic renal failure. Recent evidence, however, indicates that also in the earlier clinical phases of kidney disease, sympathetic activation is detectable. Further data show that sympathetic neural mechanisms participate in renal and/or hypertensive disease progression, favouring the development of target organ damage. Finally, recent findings indicate that the metabolic disarray frequently complicating the high blood pressure state (metabolic syndrome, dislipidemia, insulin resistance) may have as pathophysiological background a sympathetic overdrive. Altogether these data represent the rationale for employing in hypertension (and particularly in resistant hypertension) therapeutic interventions such as carotid baroreceptor stimulation and renal denervation, capable of exerting sympathoinhibitory effects. SUMMARY: The sympathetic nervous system represents a major pathophysiological hallmark of both hypertension and renal failure and is an important target for the therapeutic intervention. PMID- 22080858 TI - The complex interplay between cyclooxygenase-2 and angiotensin II in regulating kidney function. AB - PURPOSE OF REVIEW: Cyclooxygenase-2 (COX-2) plays a critical role in modulating deleterious actions of angiotensin II (Ang II) where there is an inappropriate activation of the renin-angiotensin system (RAS). This review discusses the recent developments regarding the complex interactions by which COX-2 modulates the impact of an activated RAS on kidney function and blood pressure. RECENT FINDINGS: Normal rats with increased COX-2 activity but with different intrarenal Ang II activity because of sodium restriction or chronic treatment with angiotensin-converting enzyme (ACE) inhibitors showed similar renal hemodynamic responses to COX-2-selective inhibition (nimesulide) indicating independence from the intrarenal Ang II activity. COX-2-dependent maintenance of medullary blood flow was consistent and not dependent on dietary salt or ACE inhibition. In contrast, COX-2 influences on sodium excretion were contingent on the prevailing RAS activity. In chronic hypertensive models, COX-2 inhibition elicited similar reductions in kidney function, but COX-2 metabolites contribute to rather than ameliorate the hypertension. SUMMARY: The maintenance of renal hemodynamics reflects direct and opposing effects of Ang II and COX-2 metabolites. The antagonism in water and electrolyte reabsorption is dependent on the prevailing intrarenal Ang II activity. The recent functional experiments demonstrate a beneficial modulation of Ang II by COX-2 except in the presence of inflammation promoted by hypertension, hyperglycemia, and oxidative stress. PMID- 22080860 TI - Relationship between HLA-G gene polymorphism and the susceptibility of esophageal cancer in Kazakh and Han nationality in Xinjiang. AB - OBJECTIVE: To explore the association between polymorphism of the human leukocyte antigen G (HLA-G) and susceptibility of esophageal carcinoma (EC) in Kazakh and Han nationality in Xinjiang. METHODS: The 14 bp deletion/insertion (rs16375) and 0105N (rs41557518) of HLA-G genotyping were determined by PCR and PCR-RFLP, respectively in 239 patients and 467 controls. RESULTS: There was a 2.69-fold (P(c) = 0.04, 95% CI: 1.30-5.55) increased risk of developing EC in individuals with the -14 bp/-14 bp genotype (rs16375) compared with those carrying +14 bp/+14 bp genotype in Kazakh after Bonferroni correction, there was no association of 0105N (rs41557518) both in Kazak and Han population. And there was a 2.82-fold (P(c) = 0.04, 95% CI: 1.32-6.04) increased risk of developing EC in individuals with -14 bp/-14 bp and C/C genotypes compared with those who had +14 bp/+14 bp and C/C genotypes in Kazakh. CONCLUSIONS: The study demonstrates that EC is associated with polymorphism of HLA-G14 bp in Chinese Kazak population. The 14 bp deletion/insertion of HLA-G gene may play a role in EC susceptibility of Kazakh. PMID- 22080861 TI - Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease. AB - Genome-wide association studies (GWAS) have identified a large number of SNPs that are linked to human autoimmune diseases. However, the functional consequences of most of these genetic variations remain undefined. T cell protein tyrosine phosphatase (TCPTP, which is encoded by PTPN2) is a JAK/STAT and growth factor receptor phosphatase that has been linked to the pathogenesis of type 1 diabetes, rheumatoid arthritis, and Crohn's disease by GWAS. In this issue of the JCI, Wiede and colleagues have generated a T cell-specific deletion of TCPTP and identified a novel role for this phosphatase as a negative regulator of TCR signaling. These data provide new insight as to how noncoding PTPN2 SNPs identified in GWAS could drive human autoimmune diseases. PMID- 22080862 TI - Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function. AB - Human mutations in or variants of TBX20 are associated with congenital heart disease, cardiomyopathy, and arrhythmias. To investigate whether cardiac disease in patients with these conditions results from an embryonic or ongoing requirement for Tbx20 in myocardium, we ablated Tbx20 specifically in adult cardiomyocytes in mice. This ablation resulted in the onset of severe cardiomyopathy accompanied by arrhythmias, with death ensuing within 1 to 2 weeks of Tbx20 ablation. Accounting for this dramatic phenotype, we identified molecular signatures that posit Tbx20 as a central integrator of a genetic program that maintains cardiomyocyte function in the adult heart. Expression of a number of genes encoding critical transcription factors, ion channels, and cytoskeletal/myofibrillar proteins was downregulated consequent to loss of Tbx20. Genome-wide ChIP analysis of Tbx20-binding regions in the adult heart revealed that many of these genes were direct downstream targets of Tbx20 and uncovered a previously undescribed DNA-binding site for Tbx20. Bioinformatics and in vivo functional analyses revealed a cohort of transcription factors that, working with Tbx20, integrated multiple environmental signals to maintain ion channel gene expression in the adult heart. Our data provide insight into the mechanisms by which mutations in TBX20 cause adult heart disease in humans. PMID- 22080863 TI - T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice. AB - Many autoimmune diseases exhibit familial aggregation, indicating that they have genetic determinants. Single nucleotide polymorphisms in PTPN2, which encodes T cell protein tyrosine phosphatase (TCPTP), have been linked with the development of several autoimmune diseases, including type 1 diabetes and Crohn's disease. In this study, we have identified TCPTP as a key negative regulator of TCR signaling, which might explain the association of PTPN2 SNPs with autoimmune disease. We found that TCPTP dephosphorylates and inactivates Src family kinases to regulate T cell responses. Using T cell-specific TCPTP-deficient mice, we established that TCPTP attenuates T cell activation and proliferation in vitro and blunts antigen-induced responses in vivo. TCPTP deficiency lowered the in vivo threshold for TCR-dependent CD8(+) T cell proliferation. Consistent with this, T cell-specific TCPTP-deficient mice developed widespread inflammation and autoimmunity that was transferable to wild-type recipient mice by CD8(+) T cells alone. This autoimmunity was associated with increased serum levels of proinflammatory cytokines and anti-nuclear antibodies, T cell infiltrates in non lymphoid tissues, and liver disease. These data indicate that TCPTP is a critical negative regulator of TCR signaling that sets the threshold for TCR-induced naive T cell responses to prevent autoimmune and inflammatory disorders arising. PMID- 22080864 TI - Activation of Rac1 by Src-dependent phosphorylation of Dock180(Y1811) mediates PDGFRalpha-stimulated glioma tumorigenesis in mice and humans. AB - Two hallmarks of glioblastoma multiforme, the most common malignant brain cancer in humans, are aggressive growth and the ability of single glioma cells to disperse throughout the brain. These characteristics render tumors resistant to current therapies and account for the poor prognosis of patients. Although it is known that oncogenic signaling caused by overexpression of genes such as PDGFRA is responsible for robust glioma growth and cell infiltration, the mechanisms underlying glioblastoma malignancy remain largely elusive. Here, we report that PDGFRalpha signaling in glioblastomas leads to Src-dependent phosphorylation of the guanine nucleotide exchange factor Dock180 at tyrosine 1811 (Dock180(Y1811)) that results in activation of the GTPase Rac1 and subsequent cell growth and invasion. In human glioma cells, knockdown of Dock180 and reversion with an RNAi resistant Dock180(Y1811F) abrogated, whereas an RNAi-resistant Dock180(WT) rescued, PDGFRalpha-promoted glioma growth, survival, and invasion. Phosphorylation of Dock180(Y1811) enhanced its association with CrkII and p130(Cas), causing activation of Rac1 and consequent cell motility. Dock180 also associated with PDGFRalpha to promote cell migration. Finally, phosphorylated Dock180(Y1811) was detected in clinical samples of gliomas and various types of human cancers, and coexpression of phosphorylated Dock180(Y1811), phosphorylated Src(Y418), and PDGFRalpha was predictive of extremely poor prognosis of patients with gliomas. Taken together, our findings provide insight into PDGFRalpha stimulated gliomagenesis and suggest that phosphorylated Dock180(Y1811) contributes to activation of Rac1 in human cancers with PDGFRA amplification. PMID- 22080865 TI - Loss of nuclear pro-IL-16 facilitates cell cycle progression in human cutaneous T cell lymphoma. AB - Cutaneous T cell lymphomas (CTCLs) represent a heterogeneous group of non-Hodgkin lymphomas that affect the skin. The pathogenesis of these conditions is poorly understood. For example, the signaling mechanisms contributing to the dysregulated growth of the neoplastic T cells are not well defined. Here, we demonstrate that loss of nuclear localization of pro-IL-16 facilitates CTCL cell proliferation by causing a decrease in expression of the cyclin dependent-kinase inhibitor p27Kip1. The decrease in p27Kip1 expression was directly attributable to an increase in expression of S-phase kinase-associated protein 2 (Skp2). Regulation of Skp2 is in part attributed to the nuclear presence of the scaffold protein pro-IL-16. T cells isolated from 11 patients with advanced CTCL, but not those from healthy controls or patients with T cell acute lymphocytic leukemia (T ALL), demonstrated reduction in nuclear pro-IL-16 levels. Sequence analysis identified the presence of mutations in the 5' end of the PDZ1 region of pro-IL 16, a domain required for association of pro-IL-16 with the nuclear chaperone HSC70 (also known as HSPA8). HSC70 knockdown led to loss of nuclear translocation by pro-IL-16 and subsequent increases in Skp2 levels and decreases in p27Kip1 levels, which ultimately enhanced T cell proliferation. Thus, our data indicate that advanced CTCL cell growth is facilitated, at least in part, by mutations in the scaffold protein pro-IL-16, which directly regulates Skp2 synthesis. PMID- 22080867 TI - Herpesvirus entry mediator regulates hypoxia-inducible factor-1alpha and erythropoiesis in mice. AB - Erythropoiesis, the production of red blood cells, must be tightly controlled to ensure adequate oxygen delivery to tissues without causing thrombosis or stroke. Control of physiologic and pathologic erythropoiesis is dependent predominantly on erythropoietin (EPO), the expression of which is regulated by hypoxia inducible factor (HIF) activity in response to low oxygen tension. Accumulating evidence indicates that oxygen-independent mediators, including inflammatory stimuli, cytokines, and growth factors, also upregulate HIF activity, but it is unclear whether these signals also result in EPO production and erythropoiesis in vivo. Here, we found that signaling through herpesvirus entry mediator (HVEM), a molecule of the TNF receptor superfamily, promoted HIF-1alpha activity in the kidney and subsequently facilitated renal Epo production and erythropoiesis in vivo under normoxic conditions. This Epo upregulation was mediated by increased production of NO by renal macrophages. Hvem-deficient mice displayed impaired Epo expression and aggravated anemia in response to erythropoietic stress. These data reveal that HVEM signaling functions to promote HIF-1alpha activity and Epo production, and thus to regulate erythropoiesis. Furthermore, our findings suggest that this molecular mechanism could represent a therapeutic target for Epo-responsive diseases, including anemia. PMID- 22080868 TI - Recall of false memories in individuals scoring high in schizotypy: memory distortions are scale specific. AB - BACKGROUND AND OBJECTIVES: Previous research has indicated abnormal semantic activation in individuals scoring higher in schizotypy. In the current experiment, semantic activation was examined by using the Deese-Roediger McDermott paradigm of false memories. METHODS: Participants were assessed for schizotypy using the Oxford-Liverpool Inventory of Feelings (OLIFE). Participants studied lists of semantically related words in which a critical and highly associated word was absent. Participants then recalled the list. RESULTS: Participants high in Unusual Experiences and Cognitive Disorganization recalled more critical non-presented words, weakly related studied words, and fewer studied words than participants who scored low on these measures. LIMITATIONS: Previous research using the cognitive-perceptual factor of the Schizotypy Personality Questionnaire found reduced false memories, while the Unusual Experiences subscale of the OLIFE was associated with more false memories. Both scales cover similar unusual perceptual experiences and it is unclear why they led to divergent results. CONCLUSIONS: The findings suggest that subtypes of schizotypy are associated with abnormal semantic activation. PMID- 22080866 TI - Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. AB - Individuals who are obese are frequently insulin resistant, putting them at increased risk of developing type 2 diabetes and its associated adverse health conditions. The accumulation in adipose tissue of macrophages in an inflammatory state is a hallmark of obesity-induced insulin resistance. Here, we reveal a role for AMPK beta1 in protecting macrophages from inflammation under high lipid exposure. Genetic deletion of the AMPK beta1 subunit in mice (referred to herein as beta1(-/-) mice) reduced macrophage AMPK activity, acetyl-CoA carboxylase phosphorylation, and mitochondrial content, resulting in reduced rates of fatty acid oxidation. beta1(-/-) macrophages displayed increased levels of diacylglycerol and markers of inflammation, effects that were reproduced in WT macrophages by inhibiting fatty acid oxidation and, conversely, prevented by pharmacological activation of AMPK beta1-containing complexes. The effect of AMPK beta1 loss in macrophages was tested in vivo by transplantation of bone marrow from WT or beta1(-/-) mice into WT recipients. When challenged with a high-fat diet, mice that received beta1(-/-) bone marrow displayed enhanced adipose tissue macrophage inflammation and liver insulin resistance compared with animals that received WT bone marrow. Thus, activation of AMPK beta1 and increasing fatty acid oxidation in macrophages may represent a new therapeutic approach for the treatment of insulin resistance. PMID- 22080869 TI - Individual differences in trauma disclosure. AB - BACKGROUND AND OBJECTIVES: Findings on disclosure and adjustment following traumatic events have been mixed. Better understanding of individual differences in disclosure may help us better understand reactions following trauma exposure. In particular, studying disclosure patterns for those with and without psychopathology and for different types of emotional experiences may help clarify the relationship between disclosure, event emotionality, trauma exposure, and PTSD. METHODS: In this study, 143 men and women with (n=67) and without (n=43) chronic PTSD and without trauma exposure (n=33) provided information on disclosure for a traumatic/severe life event, a negative event, and a positive event. RESULTS: Individuals with PTSD reported greater difficulty disclosing their traumatic event compared to those with trauma exposure no PTSD and those with no-trauma exposure. However, individuals with PTSD reported disclosing the traumatic event a similar number of times and with similar levels of detail to those with trauma exposure but no PTSD. Both sexual and childhood trauma were associated with greater disclosure difficulty. LIMITATIONS: Although control event types (positive, negative) were selected to control for the passage of time and for general disclosure style, they do not control for salience of the event and results may be limited by control events that were not highly salient. CONCLUSIONS: The present findings point to a dynamic conceptualization of disclosure, suggesting that the differential difficulty of disclosing traumatic events seen in individuals with PTSD is not simply a function of the amount of disclosure or the amount of details provided. PMID- 22080870 TI - Metacognitive therapy for body dysmorphic disorder patients in Iran: acceptability and proof of concept. AB - The purpose of the present study was to determine the effect of metacognitive therapy (MCT) on symptoms of body dysmorphic disorder (BDD) and on symptoms of thought-fusion, by means of a wait-list controlled clinical trial. Participants were referred from dermatology and cosmetic surgery clinics in the city of Isfahan, Iran, and 20 patients were selected on the basis of DSM-IV-TR diagnostic criteria for BDD. They were randomly assigned to either the experimental or the wait-list control group. The Yale-Brown Obsessive Compulsive Scale Modified for Body Dysmorphic Disorder (BDD-YBOCS) and the Thought-Fusion Inventory (TFI) were used as the outcome measures. The experimental group received 8 weekly metacognitive intervention sessions. The control group was in the waiting-list until the end of the follow-up. Measures were taken at pre-test, post-test (after 2 months) and follow-up (after 6-months). The results of analysis of variance showed that MCT significantly reduced the symptoms of BDD and of thought-fusion, compared to the wait-list. Effects on both outcome measures were maintained at 6 months follow-up. PMID- 22080871 TI - Image-guided robotic surgery: update on research and potential applications in urologic surgery. AB - PURPOSE OF REVIEW: New methods of imaging and image-guidance technology have the potential to provide surgeons with spatially accurate three-dimensional information about the location and anatomical relationships of critical subsurface structures and instrument position updated and displayed during the performance of surgery. Robotic platforms and technology in various forms continues to revolutionize surgery and will soon incorporate image guidance. RECENT RESEARCH: Image-guided surgery (IGS) for abdominal and urologic interventions presents complex engineering and surgical challenges along with potential benefits to surgeons and patients. Key concepts such as registration, localization, accuracy, and targeting error are necessary for surgeons to understand and utilize the potential of IGS. Standard robotic surgeries, such as partial nephrectomy and radical prostatectomy may soon incorporate IGS. SUMMARY: Research continues to explore the potential for combining image guidance and robotics to augment and improve a variety of surgical interventions. PMID- 22080872 TI - Is robotic surgery cost-effective: no. AB - PURPOSE OF REVIEW: Utilization of robotic surgery has increased dramatically in recent years, but there are significant cost implications to acquisition and utilization of robots. This review will evaluate the cost-effectiveness of using robotics in urologic surgery. RECENT FINDINGS: This study will evaluate studies comparing outcomes for open, laparoscopic and robotic procedures as well as costs associated with these procedures. SUMMARY: Current studies have not found the robotic approaches to be cost-effective. In order for the robot to be cost effective, there needs to be an improvement in efficacy over alternative approaches and a decrease in costs of the robot or instrumentation. PMID- 22080873 TI - Revival of thermotherapy for benign prostatic hyperplasia. AB - PURPOSE OF REVIEW: Transurethral resection of the prostate (TURP) has long been held as the gold standard for treatment of benign prostatic hyperplasia (BPH); however, there has been significant innovation in other less invasive alternative treatments for BPH in recent years. BPH treatment guidelines now recommend minimally invasive therapy be considered as a treatment option alongside TURP and medical management. Our purpose is to review the current evidence supporting the safety, effectiveness, and durability of transurethral microwave thermotherapy (TUMT) as a minimal invasive technique. RECENT FINDINGS: Recent clinical studies of TUMT have provided significant evidence regarding safety, efficacy, and durability. TUMT has now become a minimally invasive office-based alternative to both standard TURP and medical therapy in the treatment of bladder outlet obstruction and lower urinatry tract symptoms due to BPH. SUMMARY: TUMT treatment has improved with the advent of later generation devices. This well tolerated, effective, and durable therapy for the treatment of BPH has definitively found its place as one of the alternatives to TURP. Anestheisa-free outpatient capability, lack of sexual side-effects, and avoidance of actual surgery are attractive to patient and clinician alike. TUMT deserves reconsideration in clinical practices as a suitable treatment alternative to TURP and medical therapy. PMID- 22080874 TI - Can noninvasive evaluation of benign prostatic obstruction be optimized? AB - PURPOSE OF REVIEW: Lower urinary tract symptoms caused by benign prostatic obstruction is a common disorder and the incidence is increasing with higher life expectancy. The present article focuses on recently published methods to diagnose bladder outlet obstruction and differ between benign obstruction and prostate cancer in lower urinary tract symptoms patients. RECENT FINDINGS: Several new ultrasound imaging techniques have been reported. Resistive index in the prostatic artery, detrusor wall thickness and prostatic urethral angle all may correlate with obstruction, but more studies are needed to establish their place in clinical practice. Intravesical prostatic protrusion can predict obstruction and may be considered for clinical use. Near infrared spectroscopy has to be studied more to clarify its usefulness in clinical practice. There has been a rapid development of novel serum and urine-based biomarkers for prostate cancer in the last decade to differentiate between benign prostatic hyperplasia and prostate cancer. The recent studies with the use of prostate-specific antigen and urine prostate cancer gene 3 look promising. SUMMARY: Among promising new techniques in the investigation of prostatic obstruction, intravesical prostatic protrusion may be considered for clinical use. None of the methods described in recent studies can fully replace urodynamic investigation. Novel biomarkers in the future may help the clinicians to differentiate benign prostatic hyperplasia from prostate cancer. PMID- 22080875 TI - alpha-Blockers for benign prostatic hyperplasia: the new era. AB - PURPOSE OF REVIEW: alpha1-Adrenoceptor blockers are the most frequently prescribed medical therapy in the treatment of lower urinary tract symptom suggestive of benign prostatic hyperplasia (LUTS/BPH). The purpose of this review is to highlight the evolution of adrenoceptor blockers with emphasis on newly approved drugs. RECENT FINDINGS: Over the past years new formulations of several alpha1-adrenoceptor blockers were introduced to the market. Five long-acting alpha1-blockers are currently approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, alfuzosin and silodosin. Silodosin is the only adrenoceptor blocker that exhibits true selectivity for the alpha1-adrenoceptor subtypes. This unique adrenoceptor selectivity profile likely accounts for the very favorable cardiovascular safety profile. SUMMARY: Tamsulosin, alfuzosin slow release and silodosin do not require dose titration. Alfuzosin, terazosin, doxazosin and silodosin have all been shown to be effective in relieving LUTS/BPH independent of prostate size. Low incidence of orthostatic hypotension has been reported for silodosin, but abnormal ejaculation is the most commonly reported adverse effect. PMID- 22080876 TI - Surgeon-controlled robotic ureteral surgery. AB - PURPOSE OF REVIEW: Surgeon-controlled, robotic-assisted, ureteral reconstructive and ablative surgery is being performed routinely for both benign and malignant pathology at centers possessing this technology in their armamentarium. The aim of this review is to detail the options for surgeon-controlled robotic management of ureteral pathology and evaluate the developments in the last 2 years. RECENT FINDINGS: Surgeon-controlled robotic management of ureteric pathology involving all parts of the ureter with varying cause has been reported. Proximally, ureteral strictures and symptomatic retrocaval ureters have been repaired with long-term follow-up demonstrating resolution of obstruction. Ureterolysis and other mid-ureteral pathology have been treated with durable function results. Transitional cell carcinoma of the renal pelvis or distal ureter has been extirpated with successful oncologic outcomes. Reimplantation of refluxing ureters in children has been demonstrated to provide similar results of open surgery. SUMMARY: Surgeon-controlled, robotic-assisted ureteral surgery is well tolerated, feasible, and effective for ablative and reconstructive indications with minimal complications. Knowledge of anatomy, pathology, experience of surgical team, and appropriate preoperative patient selection augmented with proper port placement to provide excellent exposure is critical to provide optimal outcomes. PMID- 22080877 TI - Identifying clinical improvement in consolidation single-arm phase 2 trials in patients with ovarian cancer in second or greater clinical remission. AB - OBJECTIVE: Estimates of progression-free survival (PFS) from single-arm phase 2 consolidation/maintenance trials for recurrent ovarian cancer are usually interpreted in the context of historical controls. We illustrate how the duration of second-line therapy (SLT), the time on the investigational therapy (IT), and patient enrollment plan can affect efficacy measures from maintenance trials and might result in underpowered studies. METHODS: Efficacy data from 3 published single-arm consolidation therapies in second remission in ovarian cancer were used for illustration. The studies were designed to show an increase in estimated median PFS from 9 to 13.5 months. We partitioned PFS as the sum of the duration of SLT, treatment-free interval, and duration of IT. We calculated the statistical power when IT is given concurrently with SLT or after SLT by varying the start of IT. We compared the sample sizes required when PFS includes the time on SLT versus PFS that starts after SLT at initiation of IT. RESULTS: Required sample sizes varied with duration of SLT. If IT starts with initiation of SLT, only 34 patients are needed to provide 80% power to detect a 33% hazard reduction. In contrast, 104 patients are required for a single-arm study for 80% power, if IT begins 7.5 months after SLT initiation. CONCLUSIONS: Designs of nonrandomized consolidation trials that aim to prolong PFS must consider the effect of the duration of SLT on the end point definition and on required sample size. If IT is given concurrently with SLT, and after SLT, then SLT duration must be restricted per protocol eligibility, so that a comparison with historical data from other single-arm phase 2 studies is unbiased. If IT is given after SLT, the duration of SLT should be taken into account in the design stage because it will affect statistical power and sample size. PMID- 22080878 TI - Prognostic significance of lymphovascular space invasion and nodal involvement in intermediate- and high-risk endometrial cancer patients treated with curative intent using surgery and adjuvant radiotherapy. AB - OBJECTIVE: The aim of this study was to assess whether lymphovascular space invasion (LVSI) and nodal status provide adequate prognostic information in comparison with the entire set of traditional prognostic factors in intermediate- and high-risk endometrial cancer patients treated and staged with primary surgery and adjuvant radiotherapy. METHODS: Three hundred twenty-four previously untreated high-intermediate- and high-risk endometrial cancer patients with FIGO (International Federation of Gynecology and Obstetrics) stage I to IIIC; endometrioid, serous, or clear cell histology; diagnosed between November 1995 and December 2006; who presented to Peter MacCallum Cancer Centre for adjuvant radiotherapy were included in these analyses. All traditionally recognized prognostic factors and newly created 4 pairs of combination of LVSI and nodal status were studied with respect to survival and patterns of failure. RESULTS: The median follow-up time was 4.8 years. Five-year failure-free survival for all patients according to FIGO stage I, II, and III were 87.4%, 89.0%, and 62.4 %, respectively. In multivariable analysis for relapse, positive LVSI had a hazard ratio of 4.9 (P = 0.000), which increased to 8.8 (P = 0.004) in the presence of positive nodes. For overall survival, only LVSI was significant, with a hazard ratio of 3.02 (P = 0.003). In particular, in the presence of LVSI and nodes, histological type, grade, and myometrial invasion were not significant prognosticators for relapse or overall survival. CONCLUSIONS: This model enables the separation of good prognosis patients even among poorly differentiated endometrioid, serous, and clear cell carcinoma patients and can be used in simplifying the staging of endometrial cancer and for selecting patients for high risk endometrial cancer studies. PMID- 22080879 TI - LY294002 and metformin cooperatively enhance the inhibition of growth and the induction of apoptosis of ovarian cancer cells. AB - BACKGROUND: The phosphoinositide 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently aberrantly activated in ovarian cancer and confers the chemoresistant phenotype of ovarian cancer cells. LY294002 (PI3K inhibitor) and metformin (5'-adenosine monophosphate [AMP]-activated protein kinase [AMPK] activator) are 2 drugs that were known to inhibit mTOR expression through the AKT-dependent and AKT independent pathways, respectively. In this study, we explored the effectiveness of LY294002 and metformin in combination on inhibition of ovarian cancer cell growth. METHODS: Western blotting was used to detect the changes of PI3K/AKT/mTOR and AMPK/acetyl-CoA carboxylase (ACC) signaling activities, cell cycle control, and apoptosis. Cell growth was evaluated by cell proliferation, colony formation, and soft agar assays. Flow cytometry was used to study cell cycle distribution and cell death upon drug treatment. RESULTS: Our study showed that LY294002 and metformin in combination could simultaneously enhance the repression of the PI3K/AKT/mTOR pathway and the activation of the AMPK/ACC pathway. The downstream target of AKT and AMPK, mTOR, was cooperatively repressed when the drugs were used together. The cell cycle regulatory factors, p53, p27, and p21, were up regulated. On the other hand, caspase 3 and poly (ADP-ribose) polymerase activities involved in apoptosis were also activated. Cell growth assays indicated that LY294002 and metformin could effectively inhibit ovarian cancer cell growth. Flow cytometry analysis showed that the treatment of the 2 drugs mentioned above induced cell cycle arrest at G1 phase and increased sub-G1 apoptotic cells. CONCLUSION: The combinational use of LY294002 and metformin can enhance inhibition of the growth and induction of the apoptosis of ovarian cancer cells. Our results may provide significant insight into the future therapeutic regimens in ovarian cancer. PMID- 22080880 TI - Cancer stem cell and embryonic development-associated molecules contribute to prognostic significance in ovarian cancer. AB - OBJECTIVES: Embryonic molecules and cancer stem cell signaling resemble each other, and they organize cancer modality. We hypothesized that similar immunohistochemical expressions between tumor spheroids and patients' samples compared with clinical relevance would give an important clue in patients' prognosis. METHODS: Immunohistochemical expression of c-kit, Notch1, Jagged1, and Delta1 in 50 cases of primary ovarian tumors (10 endometrioid, 10 serous, 10 mucinous adenocarcinoma, 10 borderline serous, and 10 borderline mucinous tumors) and MDAH-2774 spheroids were investigated. Results were compared in both spheroids and tumor samples with morphologic parameters (histological grade) and clinical data (age, stage, tumor size, and metastasis). RESULTS: High c-kit and Notch1 immunoreactivity was shown in spheroids, but interestingly immunoreactivity of these molecules in tumor samples was different from patients' clinicopathological characteristics. In serous carcinoma, metastasis correlated with Notch1 immunoexpression; in mucinous carcinoma, Jagged1 immunohistochemistry correlated with grade, stage, and metastasis of tumor; in borderline serous and mucinous tumors, Jagged1 correlated with high grade. Moreover, Jagged1 correlated with stage and Notch1 with size in borderline mucinous tumor. Endometrioid carcinoma statistics showed that there was a correlation between age and Notch1 expression. CONCLUSION: Notch1, Jagged1, and Delta1 expressions might be useful markers for clinical prognosis of ovarian carcinomas; and Notch pathway, one of the most intensively studied putative therapeutic targets, may be a useful marker for cancer. Consequently, Jagged1 could be a marker for tumor grades and Notch1 as a marker for metastases. PMID- 22080881 TI - Radical excision of vulval disease and multidisciplinary tissue flap reconstruction: the belfast experience. AB - OBJECTIVE: The aim of this study was to compare Belfast City Hospital's vulval flap reconstructive surgery with recognized standards and published data to facilitate modifications to practice. MATERIALS AND METHODS: Retrospective cohort study involving women who underwent vulval reconstructive skin flap procedures from January 1, 2004, through December 31, 2009. RESULTS: A total of 25 women underwent 28 flaps; age range was 41 to 90 years and mean parity was 2.1. Indications for surgery were recurrence of cancer in 11 (44%) of the 25 women, benign disease in 6 women (24.0%), primary vulval cancer in another 6 women (24.0%), and vulval intraepithelial neoplasia in 2 women. Thirteen women (52.0%) within the study had undergone previous radical vulval excision. Wide local excision was performed in 14 women (56.0%), with 5 undergoing radical vulvectomy and 6 undergoing modified radical vulvectomy. There were 15 (53.6%) of the 28 lotus flaps, 6 (21.4%) rhomboid-type repairs, and 3 (10.7%) gracilus flaps.Intensive care unit admission immediately after operation was required in 2 (8.0%) of the 25 women. Return to the operating theater was required in 5 cases (20.0%). Hospital stay ranged from less than 1 week to greater than 6 weeks, the mode being 8 to 14 days and mean being 21.5 days. A total of 16 (64.0%) of the 25 cases experienced wound infection with or without breakdown, with 12 cases (48.0%) having wound infection. There were 10 cases (40.0%) of partial or complete wound breakdown. Necrosis of wound (5 cases) and lymphocyst (2 cases) were less common. Twelve women (48.0%) experienced some form of medical postoperative complication(s), whereas 15 women (60.0%) had no long-term complications. CONCLUSIONS: The rate of local flap procedure is higher than that published elsewhere, whereas the postoperative complication rate is comparable and adherent to accepted standards. Perioperative protocols have been reported to improve complication rates, and this strategy has been adopted in Belfast. PMID- 22080882 TI - Province wide clinical governance network for clinical audit for quality improvement in endometrial cancer management. AB - BACKGROUND: According to the hub-and-spoke model introduced in the Provincial Healthcare System of Reggio Emilia, early endometrial cancer is treated in peripheral low-volume hospitals (spokes) by general gynecologist, whereas more complex cancers are treated by gynecological oncologists at the main hospital (hub). OBJECTIVE: To guarantee a uniformly high standard of care to all patients with endometrial cancer treated in hub and spoke hospitals of Reggio Emilia Province. METHODS: The specialists of the 5 hospitals of Reggio Emilia Province instituted an inter hospital and multidisciplinary oncology group to write common and shared guidelines based on evidence-based medicine through the use of clinical audit. They valued the process indicators before and after guidelines introduction identifying the site of improvement and verifying the standard achievement. RESULTS: Diagnostic hysteroscopy use increased significantly from preguideline period, 53%, to postguideline period, 74%. Magnetic resonance use and accuracy increased significantly from preguideline to postguideline periods: 8.1% to 35.3% and 37.3% to 74.7%, respectively. Laparoscopy use increased from 1.6% (preguideline) to 18.6 (postguideline). Early surgical complications decreased from 16% (preguideline) to 9% (postguideline). Radiotherapy use increased from 14.% (preguideline) to 32.3% (postguideline). CONCLUSION: It is possible for a provincial oncology group to build an oncology network providing an improvement in the assistance of patients with endometrial cancer through the use of clinical audit. Clinical audit made it possible to obtain the full attendance of specialists of various disciplines involved in the treatment of endometrial cancer to optimize response time schematizing process. PMID- 22080883 TI - Severe pelvic floor symptoms after cervical cancer treatment are predominantly associated with mental and physical well-being and body image: a cross-sectional study. AB - OBJECTIVE: To identify associations between demographic, disease-related, and psychological variables and severe distress from pelvic floor symptoms (PFSs) after cervical cancer treatment. METHODS: This study was cross-sectional and questionnaire based. We included patients with cervical cancer treated between 1997 and 2007 in the Academic Medical Center, Amsterdam. Pelvic floor symptoms were assessed with urogenital distress inventory and defecatory distress inventory. Scores were dichotomized into severe (>90th percentile) versus nonsevere distress. Disease-related variables were extracted from medical files. Psychological factors included mental and physical well-being, optimism, and body image, which were assessed with standardized questionnaires. Univariate and multivariate logistic regression analyses were performed. RESULTS: A total of 282 patients were included: 148 were treated with radical hysterectomy and pelvic lymph node dissection, 61 patients were treated with surgery and adjuvant radiotherapy, and 73 patients were treated with primary radiotherapy. Demographic: Multivariate analyses showed no significant relation between demographic variables and symptoms. Disease-related: None of these variables were significantly associated in multivariate analyses. Psychosocial: In all treatment groups, multivariate associations were found. In general, better mental and physical well-being was associated with nonsevere PFSs. Increased body image disturbance was associated with severe defecation symptoms. CONCLUSIONS: Few associations were found between demographic and disease-related variables and distress from PFS after cervical cancer treatment. However, better mental and physical well-being is associated with nonsevere distress from urogenital and defecation symptoms and more body image disturbance with severe PFSs. Improving these factors might reduce distress from PFSs and should be a focus of future research. PMID- 22080884 TI - Do FIGO stage IA and small (<=2 cm) IB1 cervical adenocarcinomas have a good prognosis and warrant less radical surgery? AB - OBJECTIVES: There is a controversy regarding the optimal management of small cervical adenocarcinomas, and more radical surgery is often undertaken compared to similar size squamous carcinomas. We wished to determine the risk of parametrial involvement and metastatic disease and the outcome in International Federation of Gynecology and Obstetrics (FIGO) stage IA and small (<=2 cm) stage IB1 cervical adenocarcinomas. METHODS: All women with a diagnosis of International Federation of Gynecology and Obstetrics stages IA1, IA2, or IB1 cervical adenocarcinoma with a maximum tumor size of 2 cm were identified between 1999 and 2010 in Northern Ireland. A single pathologist reviewed all pathology prospectively at a cancer center tumor board. RESULTS: A total of 74 women were identified (mean age, 39 years; range, 25-72 years). In total, 36 women had stage IA1, 9 women had stage IA2, and 29 women had stage IB1 cervical adenocarcinomas. Surgical treatment ranged from local excision (cone or large loop excision of transformation zone) to radical hysterectomy and pelvic lymph node dissection; adjuvant therapy was not administered in any case. No parametrial involvement was seen in the 36 women who underwent parametrial resection. No lymph node metastasis was identified in the 45 women who underwent pelvic lymph node dissection. Lymphovascular space invasion was identified in 6 cases. No tumor recurrence or metastasis was noted during a mean follow-up of 35 months. CONCLUSIONS: The optimal management of women with IA or small IB1 cervical adenocarcinoma is controversial, and radical surgery is often undertaken. Our data suggest that there is an extremely low risk of parametrial and lymph node involvement with tumors 2 cm or smaller and a low recurrence rate. Less radical surgery may be warranted for small cervical adenocarcinomas, and this should be addressed by future studies. PMID- 22080885 TI - Percutaneous insertion of peritoneal ports. AB - OBJECTIVE: To describe a technique for image-guided percutaneous insertion of peritoneal ports in patients without ascites who have undergone surgical debulking for stage III ovarian cancer. MATERIALS AND METHODS: Between 2006 and 2010, 29 intraperitoneal ports were placed percutaneously in 29 patients who presented after debulking surgery for stage III ovarian cancer. Ultrasound and fluoroscopy guidance were used to assist in the port placement. RESULTS: We demonstrated a technical success rate of 100% in 29 patients. The ports remained in place for an average of 186 days; and during that time, only 2 complications (6.9%) arose. One patient presented with kinking and looping of the catheter/port reservoir connection, and the redundant loop was removed. The other patient presented with a suspected wound infection over the port pocket, and the port was removed. CONCLUSIONS: Placement of percutaneous intraperitoneal ports is feasible with an acceptably low complication rate of 6.9% in patients without abdominal ascites. PMID- 22080887 TI - Management of the elderly patient with gynecologic cancer: report of the 2011 workshop in geriatric gynecologic oncology. AB - Reflecting the worldwide aging trend and close association of aging with cancer, geriatric oncology is now growing beyond its pioneer years. Nevertheless, geriatric oncology in the gynecologic field is in the beginning stage; indeed, there is no geriatric specialist who is trained in this particular field of gynecologic oncology. Therefore, we held the first workshop in geriatric gynecologic oncology. In this review, we summarize what we discussed at the workshop and provide evidence-based recommendations for the diagnosis and treatment of gynecologic cancer in elderly individuals. PMID- 22080886 TI - Intraperitoneal chemotherapy for recurrent epithelial ovarian cancer is feasible with high completion rates, low complications, and acceptable patient outcomes. AB - OBJECTIVES: Three large randomized clinical trials have shown a survival benefit for patients treated with intraperitoneal (IP) compared with intravenous chemotherapy for advanced stage epithelial ovarian cancer (EOC). However, the use of IP chemotherapy in recurrent EOC is controversial. The purpose of this study was to determine outcomes, completion rates, and frequency of complications in patients with platinum-sensitive recurrent EOC treated with IP chemotherapy. METHODS: A retrospective, single-institution analysis of women who received IP chemotherapy for recurrent EOC from January 2003 to April 2010 was conducted. Study patients were identified from the Tumor Registry and office records. Demographic factors, stage, histology, surgical findings, cytoreduction status, and subsequent therapies were abstracted. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier methods. RESULTS: Fifty-six women who received IP chemotherapy for their first EOC recurrence were identified. The mean age of patients was 56.7 years (range, 40-79 y). Fifty-five patients (98.3%) had previously completed at least 6 cycles of intravenous chemotherapy. Of all patients, 87.5% were initially diagnosed with advanced stage disease (stage IIA IV). All patients underwent secondary cytoreduction at the time of IP port placement. Moreover, 67.9% of patients were considered optimally cytoreduced (<1 cm residual disease) at the end of the secondary debulking surgery. Forty-two patients (75%) were able to successfully complete at least 6 cycles of IP chemotherapy. Reasons for noncompletion were disease progression, allergic reaction, renal failure, pain, severe nausea and vomiting, death, and patient refusal. Six patients (10.7%) developed port complications including pain around port site, port malfunction, and port erosion into small bowel. Median PFS since the initiation of IP chemotherapy was 10.5 months (95% confidence interval, 7.5 16.4 months) and median OS was 51 months (95% confidence interval, 40.8-61.1 months). CONCLUSIONS: Intraperitoneal chemotherapy is a feasible option for patients with recurrent EOC, with high completion rates, low frequency of complications, and acceptable PFS and OS. PMID- 22080888 TI - Impact of chemotherapy-induced nausea and vomiting on quality of life in indonesian patients with gynecologic cancer. AB - BACKGROUND: Quality of life (QoL) has become a major outcome in the treatment of patients with cancer. This study is aimed at examining the impact of chemotherapy induced nausea and vomiting on QoL of patients with gynecologic cancer in Indonesia. METHODS: Chemotherapy-naive patients with gynecologic cancer, who were treated with cisplatin at a dosage 50 mg/m or higher as monotherapy or as part of combination chemotherapy regimens, were recruited in the Oncology Department, Dr. Sardjito Hospital, Yogyakarta, Indonesia. Quality of life was assessed by using the Indonesian version of the European Organization for Research and Treatment for Cancer of Quality of Life Questionnaire and Short Form-36, administered immediately before and on day 5 after chemotherapy administration. Patients used a daily diary to record nausea and vomiting during 5 days after chemotherapy. RESULTS: Most (74.9%) of the 179 patients experienced delayed emesis during the 5 days after chemotherapy despite prophylactic use of antiemetics. The delayed nausea and emesis caused significant negative impact on patients' QoL. Nausea in the delayed phase caused negative effects on patients' QoL. CONCLUSIONS: Patients reported a negative impact on the QoL of delayed emesis after chemotherapy. Poor prophylaxis of patients' nausea and vomiting after chemotherapy interferes with patients' QoL. Medical and behavioral interventions may help to alleviate the negative consequences of chemotherapeutic treatment in patients with gynecologic cancers treated with suboptimal antiemetics. PMID- 22080889 TI - Ten years' experience with centralized surgery of ovarian cancer in one health region in Norway. AB - BACKGROUND: Better outcome of advanced ovarian cancer after centralized surgery has led to the recommendation for centralized surgery in a Norwegian health region. Whether the practice pattern has changed according to this recommendation has not been examined. OBJECTIVE: The objective of this study was to evaluate the referral practice and treatment of ovarian cancer in a Norwegian health region after the introduction of centralized surgery. METHODS: This was a retrospective, population-based study, including all women undergoing surgery for primary ovarian, tubal, and peritoneal cancer between 2000 and 2005, in Health Region IV of Norway. Clinical data and data regarding treatment and 5-year follow-up were analyzed. RESULTS: In total, 279 cases of ovarian, peritoneal, and tubal cancer were included. Eighty-four percent underwent primary surgery at the teaching hospital and 16% at the nonteaching hospitals. After an immediate rise in the number of cases undergoing primary surgery at the teaching hospital after the introduction of centralization in 1995, the percentage distribution between the teaching and nonteaching hospitals was stable during the study period. The women who underwent surgery at the nonteaching hospitals had a higher percentage of early-stage disease and were at higher risk of reoperation for comprehensive staging. CONCLUSIONS: Centralization of ovarian cancer surgery has been successfully accomplished in a health region in Norway. The referral practice of assumed advanced ovarian cancer cases shows satisfactory compliance with centralization at 10 years after the implementation of centralized surgery. PMID- 22080890 TI - Surgical and oncological outcome of total laparoscopic radical hysterectomy in obese women with early-stage cervical cancer. AB - OBJECTIVE: To evaluate the clinical experience of the total laparoscopic radical hysterectomy (TLRH) for the surgical management of cervical cancer in obese (body mass index [BMI] >30 kg/m) and nonobese (BMI <30 kg/m) women. METHODS: Data were collected prospectively on intraoperative and postoperative parameters and complications for all women undergoing a TLRH for cervical cancer. Patients were classified as obese, BMI >30 kg/m, or nonobese, BMI <30 kg/m. Assessment of surgical radicality was made by comparing the excision specimens in the 2 groups with a cohort of open radical hysterectomy cases performed before the introduction of the TLRH. RESULTS: A total of 58 women underwent a TLRH; 15 (25.9%) were obese and 43 (74.1%) were in the nonobese group. There was no significant difference in intraoperative blood loss or median duration of surgery between the obese and nonobese groups. The median hospital stay in both groups was 3 days (range, 2-13 days). Four cases were converted to laparotomy (7%); all were in the nonobese group. Postoperatively, 3 patients developed ischemic ureterovaginal fistulae (5%) between days 5 and 7 after surgery; all were in the nonobese group. There was no significant difference in the parametrial length, maximum vaginal cuff length, and number of lymph nodes excised between the 2 groups. To date, there has been one recurrence during the median follow-up period of 19 months (range, 3-42 months). She belonged to the nonobese group. CONCLUSIONS: The TLRH is a surgically safe procedure for early-stage cervical cancer. Obesity did not adversely affect the performance of TLRH or the radicality of the excision. In obese women, TLRH should be the favored route of surgery for all women who require a radical hysterectomy owing to its favorable perioperative outcome and short hospital stay. PMID- 22080891 TI - An occult invasive cervical cancer found after a simple hysterectomy: a 10-year experience in a single institution. AB - OBJECTIVE: The aim of this study was to identify patients who are at risk of a recurrence and those needing adjuvant treatment by risk grouping in invasive cervical cancer after a simple hysterectomy (SH). METHODS: During 2000-2009, 26 patients who underwent SH and were finally diagnosed with stages higher than IA1 were reviewed retrospectively. The American Joint Committee on Cancer (AJCC) pathologic staging system was adopted. Based on the pathologic findings, the criteria for risk scoring was set: 1 for depth of invasion (DOI) is between 3-5 mm, and 2 for DOI greater than 5 mm; 1 for longest diameter (LD) is between 0.7 20 mm, and 2 for LD greater than 20 mm; 1 for lymphovascular space invasion positive; and 3 each for parametrium, resection margin, and lymph node positive. The final score was calculated by summing up the risk scores. The receiver operation characteristic curve was created to confirm the best cutoff value. RESULTS: All patients were stage IA2 to IB2, of which the number of patients in stages IA2, IB1, and IB2 were 1, 24, and 1, respectively. Eleven patients did not receive any further treatment. Of the remaining 15 patients, 11 received radiation therapy, 3 underwent concurrent chemoradiation therapy, and 1 received chemotherapy alone. No patient underwent a radical parametrectomy. During a median follow-up of 67 months (range, 9-122 months), 3 patients (11.5%) showed a recurrence. Patient whose score was 1 to 3, 4 to 5, and 6 or higher was classified into low-risk, intermediate-risk, and high-risk groups, respectively. All patients in the low-risk group did not recur without any adjuvant treatment (sensitivity, 100%; specificity 34.8-65.2%). CONCLUSIONS: Adjuvant treatment can be omitted in low-risk group patients with invasive cervical cancer detected after SH. PMID- 22080892 TI - Effect of obesity on survival of women with epithelial ovarian cancer: a systematic review and meta-analysis of observational studies. AB - OBJECTIVE: Although obesity is shown to be a risk factor for epithelial ovarian cancer, its role as a prognostic factor has been remained inconclusive. In this study, available evidences on this matter to date have been assembled for a meta analysis to determine the effect of obesity on the survival of patients with epithelial ovarian cancer. MATERIALS AND METHODS: Eligible studies published up to December 2010 were searched using MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials, and manual review of relevant bibliography to look for additional studies was done. Adjusted hazard ratios (HRs) from individual studies were pooled using a random-effects model. RESULTS: Ten cohort studies of 331 screened articles were included in the final analysis. The meta analysis showed overweight or obesity at early adulthood to be associated with higher mortality among patients with ovarian cancer (HR, 1.60; 95% confidence interval, 1.10-2.34). Among patients with advanced ovarian cancer, premorbid obesity was associated with worse prognosis (HR, 1.45; 95% confidence interval, 1.09-1.93). However, there was no significant relationship between prognosis and obesity around the time of diagnosis. CONCLUSIONS: This study suggests a possible relationship between obesity at early adulthood and higher mortality among patients with ovarian cancer. Further studies are needed to elucidate the harmful effect of obesity on the survival of patients with ovarian cancer. PMID- 22080893 TI - Diaphragmatic surgery during primary cytoreduction for advanced ovarian cancer: peritoneal stripping versus diaphragmatic resection. AB - BACKGROUND: Standard approach for medically stable advanced ovarian cancer patients should be primary cytoreduction following platinum-based chemotherapy. The aim of surgical effort should be the complete removal of all visible disease. Our objective was to compare perioperative features, postoperative complications, and secondarily oncological outcomes of patients who underwent diaphragmatic stripping with those who underwent diaphragmatic resection for advanced ovarian cancer. METHODS: One hundred twelve cases were identified, among them 79 underwent diaphragmatic stripping and 33 underwent diaphragmatic full-thickness resection. Data collected included patients' age, all perioperative details and pathological findings, International Federation of Gynecology and Obstetrics stage, adjuvant therapy, and follow-up data. RESULTS: Larger residual tumors (mean, 5.1 vs 1.6 mm, respectively; P < 0.01) but shorter operating time (25 minutes shorter operative time, P = 0.07) were observed in the stripping group. Higher postoperative pleural effusions rates (63.6% vs 37.9%, P = 0.01), but no differences in the remaining complications, were observed in the resection group. After a mean of 31 months of follow-up, disease-free survival rates were 27.8% in the stripping group and 39.4% in the resection group (P = 0.04). No significant differences were observed for overall survival. CONCLUSIONS: Diaphragmatic surgery at the time of primary cytoreductive surgery for advanced ovarian cancer may contribute to the achievement of complete cytoreduction with low perioperative complication rate; full-thickness resection is preferable if peritoneum stripping will not achieve a complete removal of the disease. PMID- 22080894 TI - Laparoscopic adnexal transposition: novel surgical technique. AB - Treatment of some cancers diagnosed at an early stage with expectation of prolonged survival has permitted the consideration of salvaging the reproductive and hormonal function of premenopausal female patients. When radiation to the pelvic area is part of treatment, this will almost always result in ovarian failure. To protect the ovaries, an oophoropexy may be performed, which involves moving the ovaries away from the radiation field. This procedure may be performed via laparoscopy. Some women undergoing laparoscopic radical hysterectomy may also be candidates for laparoscopic transposition. Because failure rates are still reported to be high, we developed a novel technique to mobilize the adnexa, which we present in this paper and attached movie.After separating the adnexa from the uterus and developing the infundibulopelvic (IP) ligament, a retroperitoneal tunnel is developed from the pelvis to the transposition opening laterally. The adnexa are moved through this tunnel, avoiding torsion of the vessels, and are brought through the opening back into the peritoneum. The adnexa are now fixed securely to the posterolateral abdominal wall with nonabsorbable sutures.Several issues permit better results using this technique. The IP ligament remains retroperitoneal and itself is outside the field of radiation. There is no kinking of the ovarian blood supply on the peritoneal fold. The location of the transposition is way above the field of radiation, preventing scatter injury. Even if one or both of the sutures fail, placement of the ovary will not change because of the peritoneum it has been brought through. This and the final location of the IP ligament retroperitoneally may enforce the ovary to it outside of the radiation field and prevent possible migration of the ovary back to the pelvis. This technique has advantages, which may offer the ovaries a better chance to resume hormonal function. PMID- 22080895 TI - A novel CRAd in combination with cisplatin enhanced the antitumor efficacy in ovarian cancer. AB - OBJECTIVES: The aim of this study was to investigate the combined effects of a novel survivin promoter-based conditionally replicating adenovirus (CRAd-S.RGD) plus cis-diamminedichloroplatinum (cisplatin, CDDP) in ovarian cancer in vitro and in vivo. METHODS: The viability of human ovarian cancer cell line SKOV3 was determined by MTT assay following the infection with different doses of CRAd S.RGD, either alone or in combination with CDDP. The antitumor efficacies and survival curves were evaluated at the end of the treatment regimens with the subcutaneous administration of CRAd-S.RGD, CDDP, combined therapy of CRAd-S.RGD plus CDDP, or phosphate-buffered saline in a SKOV3 xenograft animal model. Furthermore, the apoptosis rate of tumor tissues in mice was determined subsequent to the treatments. RESULTS: In vitro, the CRAd-S.RGD destroyed SKOV3 cells by oncolysis in a dose-dependent manner, and the viability of SKOV3 cells was significantly lower in the combined-therapy group than that in the individual therapy groups. In vivo, enhanced tumor inhibition and animal survival rates were obtained in a synergistic manner with CRAd-S.RGD plus CDDP, as compared with the treatment with CRAd-S.RGD or CDDP alone. There was an increase in the apoptosis rate of the cells following the combined therapy. The results clearly demonstrated that there was a synergistic effect in the combination of CRAd-S.RGD and CDDP in increased therapeutic efficacy. Similar therapeutic efficacy could be obtained with CRAd-S.RGD plus CDDP at 2 lower doses that minimized the drug toxicity to host tissues. CONCLUSIONS: The strategy of CRAd-S.RGD in combination with CDDP was a potential therapeutic modality for the therapy in ovarian cancer. ABBREVIATIONS: CDDP - cisplatin, cis-diamminedichloroplatinum, CRAd - conditionally replicating adenovirus, CRAd-survivin - the survivin promoter-based conditionally replicating adenovirus, CRAd-S.RGD - CRAd-survivin-RGD4C, MOI - multiplicity of infection, PBS - phosphate-buffered saline, PI - propidium iodide. PMID- 22080896 TI - Short-term serum deprivation confers sensitivity to taxanes in platinum-resistant human ovarian cancer cells. AB - BACKGROUND: Based on the evidences showing that serum deprivation provokes apoptosis in a variety of cells, we have investigated the effect of serum deprivation on drug sensitivity. METHODS: After human ovarian cancer cells were preincubated in 0.5 % serum containing medium for 12 hours, cellular drug sensitivities were determined by colony-forming assay. RESULTS: Serum deprivation treatment resulted in significant increase in paclitaxel sensitivity by factors of mean +/- SD, 148.6 +/- 28.1 and 10.1 +/- 1.0 (n = 3; P < 0.001) fold in platinum-resistant C13 and CP70 cells, respectively. Similarly, serum deprivation induced significant docetaxel sensitivity in these cell lines. However, no enhancement effect of serum deprivation was observed in platinum-sensitive 2008 and A2780 cells. Serum deprivation did not have any effect on the sensitivities to cisplatin, vincristin, and doxorubicin in all of these cells. More than 7-fold increase of apoptotic cells were observed in C13 or CP70 cells when they were treated by serum deprivation followed by paclitaxel compared with the treatment of either serum deprivation or paclitaxel alone. Confocal laser microscopy using rhodamine 123 and flow cytometric analysis with 3,3'-dihexyloxacarbocyanine iodide revealed that serum deprivation decreased mitochondrial membrane potential in C13 or CP70 cells, whereas no change was observed in 2008 and A2780 cells. This indicates that serum deprivation induced depolarization specifically in platinum-resistant cells. Electron microscopy revealed that serum deprivation caused regeneration of mitochondrial matrix structure in C13 or CP70 cells where mitochondria were usually destructed and disappeared. DISCUSSIONS: These results indicate that serum deprivation confers taxane hypersensitivity specifically in platinum-resistant cells by recovering their impaired mitochondrial functions. The evidence might be clinically beneficial for the development of new chemotherapeutic technology, particularly for the patients with platinum resistant ovarian cancer. PMID- 22080897 TI - IL-21 and IL-12 inhibit differentiation of Treg and TH17 cells and enhance cytotoxicity of peripheral blood mononuclear cells in patients with cervical cancer. AB - OBJECTIVES: Interleukin 21 (IL-21) and IL-12 have been known to be effective antitumor agents. In this study, we evaluated whether IL-21 in combination with IL-12 could enhance the cytotoxicity of peripheral blood mononuclear cells (PBMCs) in patients with cervical intraepithelial neoplasia III and cervical cancer. METHODS: Peripheral blood mononuclear cells were isolated from peripheral blood of cervical intraepithelial neoplasia III patients (n = 17) and cervical cancer patients (n = 18). Peripheral blood mononuclear cells were cultured with IL-2 in low concentration as control group. Interleukin 2-stimulated PBMCs were cocultured with anti-human IL-21 neutralizing antibody, IL-21 alone, IL-12 alone, and IL-21 plus IL-12, respectively, as test groups. The cytotoxicity of PBMCs against SiHa tumor cells was examined by lactate dehydrogenase released assay. CD4CD25FOXP3 T regulatory (Treg) cells and CD4IL-17A T helper 17 (TH17) cells were analyzed by flow cytometry. Proliferation and apoptosis were detected by CCK 8 (cell counting kit 8) assay and flow cytometry, respectively. RESULTS: Compared with controls, IL-21 and IL-12 significantly elevated PBMC cytotoxicity against SiHa cells. Moreover, IL-21 plus IL-12 significantly elevated PBMC cytotoxicity in comparison to IL-21 alone and IL-12 alone. We also found that IL-21 plus IL-12 significantly decreased Treg and TH17 cell proportion in comparison to controls. Notably, IL-21 plus IL-12 significantly decreased TH17 cell proportion in comparison to IL-21 alone. Both IL-21 and IL-12 significantly decreased the apoptosis rate of PBMCs, whereas neither IL-21 nor IL-12 had significant effect on PBMC proliferation. CONCLUSIONS: The combination of IL-21 and IL-12 could efficiently stimulate PBMCs with cytotoxicity against SiHa cells, and the possible mechanisms may be due to down-regulated Treg and TH17 cell differentiation. PMID- 22080899 TI - The list of prohibited substances and methods in sport: structure and review process by the world anti-doping agency. AB - The List of Prohibited Substances and Methods (the List) is the International Standard that determines what is prohibited in sport in- and out-of-competition. The official text of the List is produced by the World Anti-Doping Agency (WADA), the international independent organization responsible for promoting, coordinating and monitoring the fight against doping in sport. The drafting of the annual List is a highly interactive and consultative process involving scientific and medical experts in anti-doping, sport federations and governments. In this article, the elements that compose the List as well as the process behind its annual revision and update are presented. PMID- 22080900 TI - Investigating the use of stimulants in out-of-competition sport samples. AB - The List of Prohibited Substances and Methods (the List), an International Standard published yearly by the World Anti-Doping Agency (WADA), determines which substances and methods are prohibited in sport in- and out-of-competition. Stimulants are included within drug class S.6 under the in-competition testing section of the List. Athletes may be tempted to use stimulants as ergogenic aids in-competition in order to temporarily improve their mental and/or physical functions by increasing alertness, aggressiveness, motivation, locomotion, heart rate, and reducing fatigue. The Prohibited List Expert Group, responsible for the maintenance of the List, approved WADA funding for a two-year study to determine whether athletes were also using stimulants to benefit from their performance-enhancing effects during the training phase between competitions (i.e., out-of-competition). This study, involving 11 WADA-accredited laboratories, found that the use of stimulants by athletes during training was not significantly prevalent (0.36% of positive findings), suggesting that this issue does not, at the moment, pose a further challenge to the fight against doping in sport. In addition, the study supports the current structure in the Prohibited List that differentiates banned substances into the in- and out-of competition classifications. PMID- 22080901 TI - Identifying plasma glycerol concentration associated with urinary glycerol excretion in trained humans. AB - Glycerol has been used as a means to legitimately hyperhydrate the body in an attempt to offset the deleterious effects of dehydration. It has the potential to mask blood doping practices and as a result has been added to the WADA prohibited substance list. The purpose of this study was to identify the plasma glycerol concentration coinciding with urinary glycerol excretion. Twelve healthy, trained male subjects completed five separate trials under resting conditions. For each trial, subjects consumed a different glycerol dose (0.025, 0.05, 0.10, 0.15, or 0.20 g glycerol/kg LBM) of a 5% glycerol solution in order to determine at what plasma glycerol concentration an increase in urine glycerol concentration becomes apparent. Based on regression analysis, plasma glycerol concentrations > 0.327 +/ 0.190 mmol/L and a glycerol dose > 0.032 +/- 0.010 g glycerol/kg LBM would be associated with urinary glycerol excretion. There were significant linear relationships between peak plasma glycerol concentration and time to reach peak plasma glycerol concentration to the ingested glycerol doses. Our findings illustrate the importance of considering the effect of urinary glycerol excretion on legitimate hyperhydration regimens as well as suggesting that it is possible to detect surreptitious use of glycerol as a masking agent through urinary analysis. PMID- 22080898 TI - The androgen receptor and its use in biological assays: looking toward effect based testing and its applications. AB - Steroid abuse is a growing problem among amateur and professional athletes. Because of an inundation of newly and illegally synthesized steroids with minor structural modifications and other designer steroid receptor modulators, there is a need to develop new methods of detection which do not require prior knowledge of the abused steroid structure. The number of designer steroids currently being abused is unknown because detection methods in general are only identifying substances with a known structure. The detection of doping is moving away from merely checking for exposure to prohibited substance toward detecting an effect of prohibited substances, as biological assays can do. Cell-based biological assays are the next generation of assays which should be utilized by antidoping laboratories; they can detect androgenic anabolic steroid and other human androgen receptor (hAR) ligand presence without knowledge of their structure and assess the relative biological activity of these compounds. This review summarizes the hAR and its action and discusses its relevance to sports doping and its use in biological assays. PMID- 22080902 TI - High-performance sport, marijuana, and cannabimimetics. AB - The prohibition on use of cannabinoids in sporting competitions has been widely debated and continues to be a contentious issue. Information continues to accumulate on the adverse health effects of smoked marijuana and the decrement of performance caused by the use of cannabinoids. The objective of this article is to provide an overview of cannabinoids and cannabimimetics that directly or indirectly impact sport, the rules of sport, and performance of the athlete. This article reviews some of the history of marijuana in Olympic and Collegiate sport, summarizes the guidelines by which a substance is added to the World Anti-Doping Agency Prohibited List, and updates information on the pharmacologic effects of cannabinoids and their mechanism of action. The recently marketed cannabimimetics Spice and K2 are included in the discussion as they activate the same receptors as are activated by THC. The article also provides a view as to why the World Anti-Doping Agency prohibits cannabinoid or cannabimimetic use incompetition and should continue to do so. PMID- 22080903 TI - Screening indicators of dehydroepiandosterone, androstenedione, and dihydrotestosterone use: a literature review. AB - Because of their perceived and reported effects on self-image, muscle development, performance, and similar factors, anabolic-androgenic steroids (AAS) and their precursors are among the most abused substances by professional, amateur, and recreational athletes. However, AAS abuse is not limited to athletes, but is also prevalent in the workplace, especially those professions in which image, strength, and endurance are coveted attributes. The detection of many steroids in biological specimens is analogous to the detection of an abused drug such as cocaine. Identification of the parent drug or its characteristic metabolite(s) in a donor's sample with a drug screening technique and confirmation of the drug/metabolite with a suitable alternative technology provides evidence of use. These analyses and subsequent interpretive scenarios become far more complex when the ingested AAS is an endogenous compound such as dehydroepiandrosterone (DHEA), androstenedione (Adione), or dihydrotestosterone (DHT). These compounds and their metabolites are present in specimens such as urine as a course of our natural endocrine function. Therefore, it becomes much more challenging for the laboratory to establish testing and interpretative paradigms that can distinguish "normal" urinary profiles of these steroids and their metabolites from profiles indicative of exogenous use. Distinguishing "normal" from "abnormal" urine profiles is particularly challenging during screening when literally tens of steroids and their metabolites may be tested simultaneously in a single chromatographic analysis. The purpose of this paper is to review the relevant literature about DHEA, Adione, and DHT administration, detection, and interpretation specifically as it relates to changes in the urinary AAS profile that may be identified during the routine laboratory screening of donor urine specimens. PMID- 22080904 TI - Validation of a liquid chromatography-tandem mass spectrometry method for quantification of glycopyrrolate in horse plasma. AB - A rapid, sensitive, and specific ultra-high-performance liquid chromatography with heated electrospray ionization-tandem mass spectrometry (UHPLC-HESI-MS-MS) method to detect and quantify glycopyrrolate in horse plasma has been developed and validated. We also determined glycopyrrolate in plasma after oral and intravenous administration of clinically relevant doses to Thoroughbred horses. Calibration was accomplished by weighted, linear regression analysis using a deuterated analogue of glycopyrrolate as internal standard (IS). Glycopyrrolate (GLY) and the IS (GLY-d(3)) were isolated from plasma matrices via weak cation exchange using a simple solid-phase extraction technique. Chromatographic analysis was achieved by reversed-phase UHPLC on a C(18) AcquityTM column. Extracts were analyzed in positive electrospray ionization mode and precursor and product ions were detected and quantified by MS-MS using a triple-stage quadrupole (TSQ) instrument. The method was characterized by a linear range of 0.125-25 pg/mL (R(2) > 0.998), a lower limit of quantification of 0.125 pg/mL and a lower limit of detection of 0.025 pg/mL. Recovery of GLY ranged from 78% to 96%, and intra- and interbatch precision were 3.3-14.4%CV and 3.4-14.4%CV, respectively. Glycopyrrolate was stable in plasma for up to 170 days at -80 degrees C, through three freeze/thaw cycles, and for up to 48 h after extraction under 20 degrees C autosampler conditions. PMID- 22080905 TI - Liquid chromatography-tandem mass spectrometry screening method for the simultaneous detection of stimulants and diuretics in urine. AB - This study established a simultaneous screening method based on solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS-MS) for the detection of 23 stimulants and 23 diuretics in human urine. An electrospray ionization source and multiple reaction monitoring were used for data acquisition. All stimulants and diuretics were separated in less than 12.52 min. The limits of detection were in the range of 25-500 ng/mL for stimulants and 25 125 ng/mL for diuretics. To evaluate the performance of this method, urine samples were collected from 1627 athletes in Taiwan, and 7 positive samples were found. This LC-MS-MS method not only meets the minimum required performance limits set by the World Anti-Doping Agency but also provides a fast way to analyze the authentic urine samples in doping control laboratories. PMID- 22080906 TI - Choroid is thinner in inferior region of optic disks of normal eyes. AB - PURPOSE: To determine the thickness of the choroid across the posterior pole of normal eyes. METHODS: Twenty-eight clinic-based normal eyes (54.1 +/- 20.0 years, -3.6 +/- 4.1 diopter) were studied. The macula and retina around the optic disk were scanned with a spectral-domain optical coherence tomographic instrument. The retinal mapping program with the enhanced depth imaging technique was used, and the borders of the choroid were drawn manually in each optical coherence tomographic image. A choroidal thickness map was constructed by the built-in program, and the choroidal thickness in the different sectors of the Early Treatment Diabetic Retinopathy Study grid was measured and compared. RESULTS: The choroid inferior to the optic disk was significantly thinner than that in the other sectors of the outer ring of the Early Treatment Diabetic Retinopathy Study grid (superior, 196 +/- 62 MUm; inferior, 146 +/- 47 MUm; nasal, 183 +/- 80 MUm; and temporal, 193 +/- 64 MUm, P < 0.001). The mean choroidal thickness at the nasal sector of the macular region was significantly thinner than other regions of the Early Treatment Diabetic Retinopathy Study grid (superior, 268 +/- 74 MUm; inferior, 245 +/- 73 MUm; nasal, 190 +/- 68 MUm; temporal, 268 +/- 63 MUm; and central, 258 +/- 88 MUm; P < 0.05). Choroidal thickness maps showed that the thinner choroidal area spreads around the optic disk and the inferior part of the posterior pole. CONCLUSION: The thinner choroid inferior to the optic disk may be a natural anatomical architecture of normal eyes, and this area may be more susceptible to hypoxia or to elevated intraocular pressures. PMID- 22080907 TI - Toxicity and retinal penetration of infliximab in primates. AB - PURPOSE: To evaluate the retinal penetration and toxicity of two doses of intravitreal infliximab in primates. METHODS: Ten marmosets (Callithrix jacchus) were given intravitreal injection of 100 MUg or 400 MUg of infliximab, and balanced salt solution served as control. At baseline and after 24 hours (5 animals) and 7 days (the other 5), the eyes were examined by electroretinography. They were then killed (at 24 hours and 7 days) and assessed by light microscopy and transmission electron microscopy for toxicity and immunohistochemistry, using a biotinylated anti-human immunoglobulin G, to evaluate retinal penetration. RESULTS: There was no difference over 50% of the electroretinography b-wave between baseline and the time points studied in all animals. Light and electron microscopy, and electroretinography analysis, showed no signs of toxicity in any of the animals. Strong presence of infliximab was observed in all retinal layers 7 days after intravitreal injection at both doses (100 and 400 MUg). CONCLUSION: Infliximab at doses of 100 and 400 MUg seemed to cause no damage to the retina 24 hours and 7 days after its intravitreal injection, and deeply penetrated all its layers, in primates. These results encourage future perspectives for the treatment of chronic inflammatory diseases of the retina in humans. PMID- 22080908 TI - Familial trends in a population with macular holes. AB - PURPOSE: To determine if patients with macular hole report an increased family history of macular hole compared with control patients and compare the report of family history between patients with unilateral and bilateral macular holes. METHODS: This was a multicenter case-control study. Charts of patients coded with diagnosis of macular hole were reviewed, and the diagnosis of idiopathic full thickness macular hole was ascertained in 166 patients. The control group comprised 136 patients without macular hole or trauma who presented with senile cataract. Family history was obtained from all patients through a telephone interview. RESULTS: Six of 166 (3.6%) macular hole patients surveyed reported a history of macular hole in a primary relative compared with none of 136 (0.0%) control patients (odds ratio is infinity, with 95% confidence interval 1.295 to infinity); however, this finding may be explained by confounders such as age and number of family members. Two of the 142 (1.4%) patients with unilateral holes versus 4 of the 24 (16.7%) patients with bilateral holes reported a family history (odds ratio is 0.0714, with 95% confidence interval 0.0063 to 0.5537), and this finding remains significant when logistic regression is performed to evaluate variables of age and number of family members as potential confounders. CONCLUSION: There is an increased report of familial occurrence of macular hole in patients with macular holes compared with control patients; however, logistic regression relates this finding to variables of age and number of family members. Patients with bilateral macular holes are more likely to report a family history of macular hole than patients with unilateral macular holes, and this finding remains significant in the presence of age and number of family members. These findings may suggest a familial component to macular hole. PMID- 22080909 TI - Diagnostic and therapeutic challenges. PMID- 22080910 TI - Thermal deformation of chandelier endoillumination probes exposed to uveal tissue and blood. AB - PURPOSE: The purpose of this study was to evaluate the characteristics and thermal properties of a chandelier endoillumination probe under conditions that may induce thermal damage. METHODS: Experimental evaluation of a surgical ophthalmic instrument under ex vivo conditions. RESULTS: A 27-gauge dual-tip chandelier endoillumination probe was exposed to air, saline, porcine uveal tissue, and human blood using a Xenon light source at 100% intensity. No alteration of probe tip morphology was observed in air or saline at 10-minute exposure. After exposure to uveal tissue and blood, thermal melting of the probe tip was noted at 10 minutes. Beam focus and intensity were observed to diminish in the probe tips that underwent thermal melting. A thermal imaging device was used to demonstrate increased thermal intensity from the probe tip that had been covered with uveal tissue compared with a control tip in air. CONCLUSION: Thermal melting of a chandelier fiber probe has been reported only once previously in the literature after exposure to porcine Tenon capsular tissue. We report two separate conditions that may induce thermal damage to a fiber optic probe including encapsulation of uveal tissue at the probe tip and exposure to blood. Vitreoretinal surgeons should be aware of this potential complication. PMID- 22080911 TI - Ultra-wide-field angiography improves the detection and classification of diabetic retinopathy. AB - PURPOSE: To evaluate patients with diabetic retinopathy using ultra-wide-field fluorescein angiography and to compare the visualized retinal pathology with that seen on an overly of conventional 7 standard field (7SF) imaging. METHODS: Two hundred and eighteen eyes of 118 diabetic patients who underwent diagnostic fluorescein angiography using the Optos Optomap Panoramic 200A imaging system were included. The visualized area of the retina, retinal nonperfusion, retinal neovascularization, and panretinal photocoagulation were quantified by two independent masked graders. The respective areas identified on the ultra-wide field fluorescein angiography image were compared with an overly of a modified 7SF image as outlined in the Early Treatment Diabetic Retinopathy Study. RESULTS: Ultra-wide-field fluorescein angiograms imaging, on average, demonstrated 3.2 times more total retinal surface area than 7SF. When compared with 7SF, ultra wide-field fluorescein angiography showed 3.9 times more nonperfusion (P < 0.001), 1.9 times more neovascularization (P = 0.036), and 3.8 times more panretinal photocoagulation (P < 0.001). In 22 eyes (10%), ultra-wide-field fluorescein angiography demonstrated retinal pathology (including nonperfusion and neovascularization) not evident in an 7SF overly. CONCLUSION: Compared with conventional 7SF imaging, ultra-wide-field fluorescein angiography reveals significantly more retinal vascular pathology in patients with diabetic retinopathy. Improved retinal visualization may alter the classification of diabetic retinopathy and may therefore influence follow-up and treatment of these patients. PMID- 22080912 TI - Changes in visual acuity and foveal photoreceptor integrity in eyes with chronic cystoid macular edema associated with retinal vein occlusion. AB - PURPOSE: To investigate the change in integrity and thickness of the foveal outer retina in eyes with chronic cystoid macula edema associated with retinal vein occlusion. METHODS: We reviewed retrospectively the medical records of 30 eyes of 30 patients who had chronic cystoid macula edema associated with retinal vein occlusion and who had a follow-up of more than 12 months without any treatment. Using optical coherence tomography, we assessed the thickness of the outer retina and status of the junction between the inner and outer segments of the photoreceptors and of the external limiting membrane in the fovea. RESULTS: Visual acuity showed a correlation with thickness of the foveal outer retina (R = -0.37) and with the detection of a line of the inner and outer segments of the photoreceptors (R = 0.65) and that of an external limiting membrane (R = 0.75) beneath the fovea. During the observation period (17.2 +/- 5.5 months), neither visual acuity nor the condition of the foveal outer retina showed a significant change, and in no eyes were previously detectable lines of the inner and outer segments of the photoreceptors and external limiting membrane just beneath the foveal cystoid space became undetectable. CONCLUSION: Even if a large cystoid space is located in the fovea, its effect on deterioration of the underlying foveal photoreceptor cells is not as strong as is generally thought. PMID- 22080913 TI - Fundus autofluorescence in serpiginouslike choroiditis. AB - PURPOSE: To report the fundus autofluorescence characteristics in serpiginouslike choroiditis. METHODS: Twenty-nine patients with presumed tubercular serpiginouslike choroiditis between November 2008 and January 2010 underwent fundus autofluorescence imaging during the acute stage and at regular intervals till the lesions healed. All patients received antitubercular therapy with oral corticosteroids. The autofluorescence images were compared with color fundus photography and fundus fluorescein angiography. The main outcome measure was fundus autofluorescence characteristics of lesions during the course of the disease. RESULTS: The pattern of fundus autofluorescence changed as the lesions evolved from the acute to the healed stage. In acute stage, the lesions showed an ill-defined halo of increased autofluorescence (hyperautofluorescence), giving it a diffuse, amorphous appearance (Stage I, acute). As the lesions began to heal, a thin rim of decreased autofluorescence (hypoautofluorescence) surrounded the lesion, defining its edges. The lesions showed predominantly hyperautofluorescence with stippled pattern (Stage II, subacute). With further healing, the hypoautofluorescence progressed and the lesion appeared predominantly hypoautofluorescent with stippled pattern (Stage III, nearly resolved). On complete healing, the lesions became uniformly hypoautofluorescent (Stage IV, completely resolved). CONCLUSION: Fundus autofluorescence highlighted the areas of disease activity and was a quick imaging tool for monitoring the course of lesions in serpiginouslike choroiditis. PMID- 22080914 TI - Vitrectomy without face-down posturing for idiopathic macular holes. AB - PURPOSE: To report the results of vitrectomy with internal limiting membrane peeling and C3F8 tamponade for macular hole without postoperative face-down posturing in 208 eyes. METHODS: The study included 208 eyes on an uncontrolled retrospective review, undergoing pars plana vitrectomy with trypan blue-assisted internal limiting membrane peeling and C3F8 tamponade, without subsequent face down posturing. All patients were followed-up at 1 day, 1 week, 3 months, and 12 months postoperatively. Biomicroscopy and optical coherence tomography were used to assess macular hole closure at 1 day, 1 week, 3 months, and 12 months postoperatively. Pre- and postoperative visual acuity by Snellen chart was compared. RESULTS: In 208 eyes with idiopathic macular hole, preoperative mean visual acuity was 20/200 and final visual acuity was 20/40 (P = 0.00017). Anatomic macular hole closure rate was 81.3%. CONCLUSION: In agreement with published studies, combined phacovitrectomy without face-down posturing after macular hole surgery seems effective and safe, showing anatomical improvement and favorable best-corrected visual acuity. Isolating the macula from vitreous fluid with a large long-lasting gas-fill may render postoperative posturing unnecessary. Eliminating face-down posturing may increase patient acceptance and compliance. PMID- 22080916 TI - Can erectile function be predicted after prostate cancer treatment? PMID- 22080915 TI - Metabolic function of a suboptimal transplanted islet mass in nonhuman primates on rapamycin monotherapy. AB - Although islet transplantation may restore insulin independence to individuals with type 1 diabetes mellitus, most have abnormal glucose tolerance. We asked whether the defective glucose tolerance is due to inadequate beta-cell mass or to impaired insulin sensitivity. We performed metabolic studies on four cynomolgus primates before inducing diabetes with streptozotocin (STZ), then again 2-3 weeks after restoring insulin independence via intrahepatic islet transplantation utilizing a calcineurin inhibitor-free immunosuppressive regimen (induction with rabbit antithymocyte globulin and maintenance therapy with rapamycin). Engrafted beta-cell mass was assessed by acute insulin and C-peptide responses to glucose (AIR(glu) and ACR(glu)) and arginine (AIR(arg) and ACR(arg)). Insulin sensitivity (S(I)) was determined in naive and transplanted primates from an intravenous glucose tolerance test using the minimal model. alpha-Cell function was determined by the acute glucagon response to arginine (AGR(arg)). Glucose tolerance (K(g)) decreased from 4.1 +/- 0.5%/min in naive primates to 1.8 +/- 0.3%/min in transplanted primates (p < 0.01). Following transplantation, AIR(glu) was 28.7 +/- 13.1 MUU/ml compared to 169.9 +/- 43.1 MUU/ml (p < 0.03) in the naive condition, ACR(glu) was 14.5 +/- 6.0 ng/ml compared to 96.5 +/- 17.0 ng/ml naive (p < 0.01), AIR(arg) was 29.1 +/- 13.1 MUU/ml compared to 91.4 +/- 28.2 MUU/ml naive (p < 0.05), and ACR(arg) was 1.11 +/- 0.51 ng/ml compared to 2.79 +/ 0.77 ng/ml naive (p < 0.05). S(I) did not differ from naive to posttransplant states. AGR(arg) was reduced in transplanted primates (349 +/- 118 pg/ml) when compared to both naive (827 +/- 354 pg/ml) and post-STZ diabetic primates (1020 +/- 440 pg/ml) (p < 0.01 for both comparisons). These data suggest that impaired glucose tolerance observed in islet transplant recipients is secondary to low functional beta-cell mass and not to insulin resistance shortly after transplant. Furthermore, improved glycemic control achieved via islet transplantation over the diabetic state might be attained, in part, via reduced glucagon secretion. PMID- 22080917 TI - Intramolecular signaling in tandem-GAF domains from PDE5 and PDE10 studied with a cyanobacterial adenylyl cyclase reporter. AB - The dimeric mammalian phosphodiesterases (PDEs) are regulated by N-terminal domains. In PDE5, the GAF-A subdomain of a GAF-tandem (GAF-A and -B) binds the activator cGMP and in PDE10 GAF-B binds cAMP. GAF-tandem chimeras of PDE5 and 10 in which the 36 aa linker helix between GAF-A and -B was swapped lost allosteric regulation of a reporter adenylyl cyclase. In 16 consecutive constructs we substituted the PDE10 linker with that from PDE5. An initial stretch of 10 amino acids coded for isoform specificity. A C240Y substitution uncoupled cyclase activity from regulation, whereas C240F, L or G did not. The C240Y substitution increased basal activity to stimulated levels. Notably, over the next 12 substitutions basal cyclase activity decreased linearly. Further targeted substitutions were based on homology modeling using the PDE2 structure. No combination of substitutions within the initial 10 linker residues caused loss of regulation. The full 10 aa stretch was required. Modeling indicated a potential interaction of the linker with a loop from GAF-A. To interrupt H-bonding a glycine substitution of the loop segment was generated. Despite reduction of basal activity, loss of regulation was maintained. Possibly, the orientation of the linker helix is determined by formation of the dimer at the initial linker segment. Downstream deflections of the linker helix may have caused loss of regulation. PMID- 22080918 TI - 17-Hydroxy-jolkinolide B, a diterpenoid from Euphorbia fischeriana, inhibits inflammatory mediators but activates heme oxygenase-1 expression in lipopolysaccharide-stimulated murine macrophages. AB - Jolkinolides are the main abietane-type diterpenoids isolated from the root of Euphorbia fischeriana Steud. In the present study, we investigated in vitro anti inflammatory activity of four structural analogs of jolkinolide in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. Among these jolkinolides, 17-hydroxy-jolkinolide B (HJB) exhibited the most potent inhibition of LPS induced production of inflammatory mediators such as prostaglandin E(2) (PGE(2)), nitric oxide (NO), and pro-inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)]. HJB could decrease LPS-induced protein levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and the mRNA expressions of COX-2, iNOS, IL-6, and TNF-alpha in a concentration-dependent manner. These inhibitory effects were caused by suppression of MAPK phosphorylation and NF-kappaB activation. Furthermore, we demonstrated that HJB strongly induced heme oxygenase-1 (HO-1) protein and mRNA expressions. These findings suggest that HJB possesses anti-inflammatory actions in macrophages and may provide a potential therapeutic approach for inflammatory disorders. PMID- 22080919 TI - Cyclic electron flow plays an important role in photoprotection for the resurrection plant Paraboea rufescens under drought stress. AB - Resurrection plants could survive severe drought stress, but the underlying mechanism for protecting their photosynthetic apparatus against drought stress is unclear. Cyclic electron flow (CEF) has been documented as a crucial mechanism for photoprotection in Arabidopsis and tobacco. We hypothesized that CEF plays an important role in protecting photosystem I (PSI) and photosystem II (PSII) against drought stress for resurrection plants. To address this hypothesis, the effects of mild drought stress on light energy distribution in PSII and P700 redox state were examined in a resurrection plant Paraboea rufescens. Cyclic electron flow was not activated below the photosynthetic photon flux density (PPFD) of 400 MUmol m-2 s-1 in leaves without drought stress. However, CEF was activated under low light in leaves with mild drought stress, and the effective quantum yield of PSII significantly decreased. Meanwhile, non-photochemical quenching (NPQ) was significantly stimulated not only under high light but also under low light. Compared with the control, the fraction of overall P700 that cannot be oxidized in a given state (PSI acceptor side limitation) under high light was maintained at low level of 0.1 in leaves with water deficit, indicating that the over-reduction of the PSI acceptor side was prevented by the significant stimulation of CEF. Furthermore, methyl viologen could significantly increase the PSII photo-inhibition induced by high light compared with chloramphenicol. These results suggested that CEF is an important mechanism for protecting PSI and PSII from drought stress in resurrection plants. PMID- 22080920 TI - TGF-beta induces the expression of the adaptor Ndfip1 to silence IL-4 production during iTreg cell differentiation. AB - Mice deficient in the adaptor Ndfip1 develop inflammation at sites of environmental antigen exposure. We show here that such mice had fewer inducible regulatory T cells (iT(reg) cells). In vitro, Ndfip1-deficient T cells expressed normal amounts of the transcription factor Foxp3 during the first 48 h of iT(reg) cell differentiation; however, this expression was not sustained. Abortive Foxp3 expression was caused by production of interleukin 4 (IL-4) by Ndfip1(-/-) cells. We found that Ndfip1 expression was transiently upregulated during iT(reg) cell differentiation in a manner dependent on transforming growth factor-beta (TGF beta). Once expressed, Ndfip1 promoted degradation of the transcription factor JunB mediated by the E3 ubiquitin ligase Itch, thus preventing IL-4 production. On the basis of our data, we propose that TGF-beta signaling induces Ndfip1 expression to silence IL-4 production, thus permitting iT(reg) cell differentiation. PMID- 22080922 TI - Peripheral arterial disease in women. AB - Women with peripheral arterial disease (PAD) are not well identified in cardiology practice, are undertreated, and have different relative risks for development of PAD than men. Recognizing that PAD is considered a coronary artery disease risk equivalent emphasizes that primary care physicians and cardiologists need to be aggressive for screening and treatment of this disorder. This article reviews the prevalence and risk factors for PAD in women, sex-based differences in development of PAD, and current screening and treatment recommendations. PMID- 22080921 TI - Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis. AB - Cell fate depends on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2beta nucleosome-remodeling and histone-deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid lineage-determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethered this complex to active genes encoding molecules involved in lymphoid differentiation. Loss of Ikaros DNA-binding activity caused a local increase in chromatin remodeling and histone deacetylation and suppression of lymphoid cell-specific gene expression. Without Ikaros, the NuRD complex also redistributed to transcriptionally poised genes that were not targets of Ikaros (encoding molecules involved in proliferation and metabolism), which induced their reactivation. Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks. PMID- 22080923 TI - Hypoglycemia and adverse outcomes: marker or mediator? AB - Multiple studies have shown that hypoglycemia is associated with increased mortality and a variety of adverse outcomes. Whether hypoglycemia is a mediator of adverse outcomes or simply represents a marker of critical illness has been unclear until now. Based on observational data, spontaneous (but not iatrogenic) hypoglycemia is associated with increased mortality during hospitalization for acute myocardial infarction. In the recent ADVANCE trial of patients with diabetes, intensive glucose lowering was associated with increased risk of hypoglycemia. Hypoglycemia was, in turn, associated with increased risk of macro- and microvascular events and death, and also with increased risk of noncardiac adverse events, including disorders of the digestive, respiratory, and skin systems. Based on available evidence, hypoglycemia does not appear to directly lead to death or cardiovascular events and is likely a marker for more severe illness and comorbidity burden. Nevertheless, continued efforts to avoid hypoglycemia are clearly warranted. PMID- 22080924 TI - The electrophysiological properties of ranolazine: a metabolic anti-ischemic drug or an energy-efficient antiarrhythmic agent? AB - Ranolazine, a newer anti-ischemic agent that appears to induce a more efficient utilization of adenosine triphosphate at the cellular level, has been shown to be clinically beneficial in patients with chronic stable angina. More recently, the antiarrhythmic effects of the drug have been described in patients with acute coronary syndromes, as well as in those with atrial fibrillation, when combined with other agents. Experimentally, the predominant inhibitory effects on late I(Na), I(Ca), I(Na-Ca), and I(Ks), with little or no effect on I(to) or I(K1), have been demonstrated. Different experimental models have shown the potential beneficial effect of the drug in both supraventricular and ventricular arrhythmias. Interestingly, despite its potential prolongation of the QT interval, ranolazine does not appear to induce ventricular arrhythmias in animal models. Whether the antiarrhythmic effect is secondary to a more efficient energy production by the cardiac cell or by its direct effect on ion channels is still unclear. The effect of ranolazine on other ionic currents, as well as its potential as a clinically relevant antiarrhythmic agent, still needs to be studied. PMID- 22080925 TI - Cardiac allograft vasculopathy. AB - Cardiac allograft vasculopathy (CAV) is the most important cause of morbidity and mortality following cardiac transplantation. CAV is largely mediated by immunologic damage and infiltration of the endothelium, resulting in proliferation of vascular smooth muscle cells and subsequent luminal narrowing. There are various risk factors for the development and progression of CAV. Coronary angiography is the gold standard for the diagnosis of CAV; intravascular ultrasound also plays an important role. The management of CAV includes immunosuppression, drugs that modify conventional coronary artery disease risk factors, and percutaneous coronary intervention (PCI) or surgical revascularization for severe obstructive lesions. Although revascularization with PCI has a high immediate success rate, rates of in-stent restenosis are higher as compared with PCI of native coronary arteries, although the advent of drug eluting stents has somewhat improved in-stent restenosis rates. Thus, the only definitive treatment of CAV is repeat transplantation. Randomized trials are needed to determine the optimal immunosuppressive and conventional risk factor modifying agents and revascularization strategies for patients who develop CAV. PMID- 22080927 TI - The changing landscape of cardiovascular care. PMID- 22080926 TI - Pending plans for payment alignment. PMID- 22080928 TI - Takotsubo cardiomyopathy due to iatrogenic methadone withdrawal. AB - Takotsubo cardiomyopathy is a syndrome characterized by transient apical ballooning or reversible midventricular systolic dysfunction. Most cases occur in postmenopausal women and are typically triggered by an acute medical illness or emotional or physical stress. Its presentation is highly suggestive of myocardial ischemia, but there is little or no evidence of epicardial coronary artery disease. To our knowledge there are only three reported cases in the literature of Takotsubo cardiomyopathy induced by opioid agonist withdrawal in adults; ours is the first reported case of iatrogenic methadone withdrawal leading to Takotsubo cardiomyopathy. PMID- 22080929 TI - Cardiovascular mortality in chronic kidney disease patients undergoing percutaneous coronary intervention. PMID- 22080931 TI - Effects of microendoscopy-assisted reduction and screw fixation through a single mini-incision on posterior cruciate ligament tibial avulsion fracture. AB - INTRODUCTION: There are various surgical approaches for the treatment of posterior cruciate ligament (PCL) injury-associated tibial fracture avulsion, including arthroscopy-assisted surgery and open posterior surgery. However, none of these treatments are perfect. We have established a simple procedure with microendoscopy-assisted reduction and cannulated screw fixation for the treatment of this disease through a single mini-incision. In this study, we delineated the effects of this surgical approach for patients with PCL tibial avulsion fracture. PATIENTS AND METHODS: We retrospectively reviewed 24 patients with acute PCL tibial avulsion fracture treated via this method from 2004 to 2008. All the patients were implanted with cannulated screws (AO/ASIF, 3.5, 4.0 or 4.5 mm in diameter, 3-4 mm in length) for fixation by microendoscopy. The posterior drawer test (PDT) and KT-2000 arthrometer examination were performed to evaluate knee stability. The Lysholm knee scoring scale and the International Knee Documentation Committee (IKDC) scoring scale were used to assess knee function. Types and rates of complications and radiographic follow-up were reviewed for all cases. RESULTS: 23 of 24 cases achieved knee stability by PDT and KT-2000 examination. The Lysholm's score was improved from 43.8 +/- 4.6 to 95.3 +/- 3.8. The IKDC evaluation demonstrated an improved function in 17 cases with grade A, 6 with grade B, and 1 with grade C. No relevant complications were experienced by any patient. CONCLUSIONS: Increased stability, functional improvement, and few complications were observed in patients of PCL injury-associated tibial fracture avulsion treated with the microendoscopy-assisted reduction and cannulated screw fixation through a single mini-incision. PMID- 22080932 TI - Posterior root tear fixation of the lateral meniscus combined with arthroscopic ACL double-bundle reconstruction: technical note of a transosseous fixation using the tibial PL tunnel. AB - According to our observation in ACL reconstruction, we find root tears of the posterior horn of the lateral meniscus as a common concomitant injury in ACL deficient knees. This might be a consequence of initial trauma or of the increased anterior-posterior translation of the tibia and an overload impact on the posterior meniscus root in ACL-deficient knees. A tear of the posterior horn of the medial meniscus causes a 25% increase in peak pressure in the medial compartment compared with that found in the intact condition. The repair restores the peak contact pressure to normal (Allaire et al. in J Bone Joint Surg Am 90(9):1922-1931, [2008]). A tear of the posterior horn of the lateral meniscus might have similar consequences. We hypothesize the surgical anatomical reattachment of the root at the tibia helping to restore knee joint kinematics and helping to advance ACL-graft function. This article presents an arthroscopical technique to reattach the posterior meniscus root in combination with ACL double-bundle reconstruction. The procedure uses the tibial PL tunnel to fix the meniscus suture. PMID- 22080930 TI - The myriad roles of cyclic AMP in microbial pathogens: from signal to sword. AB - All organisms must sense and respond to their external environments, and this signal transduction often involves second messengers such as cyclic nucleotides. One such nucleotide is cyclic AMP, a universal second messenger that is used by diverse forms of life, including mammals, fungi, protozoa and bacteria. In this review, we discuss the many roles of cAMP in bacterial, fungal and protozoan pathogens and its contributions to microbial pathogenesis. These roles include the coordination of intracellular processes, such as virulence gene expression, with extracellular signals from the environment, and the manipulation of host immunity by increasing cAMP levels in host cells during infection. PMID- 22080933 TI - Hearing threshold levels at age 70 years (65-74 years) in the unscreened older adult population of the United States, 1959-1962 and 1999-2006. AB - OBJECTIVES: To provide hearing threshold percentiles from unscreened older adults for creating new Annex B reference standards. DESIGN: Percentiles are calculated, and 95% confidence intervals for medians from two U.S. surveys are compared graphically. RESULTS: Median thresholds are lower (better) in the 1999-2006 National Health and Nutrition Examination Survey for men across all frequencies except 1 kHz. Results for women are similar; however, there is more overlap in confidence intervals across frequencies. CONCLUSIONS: The prevalence of hearing impairment in older adults, age 70 years (65-74 years), is lower in 1999-2006 compared with 1959-1962, consistent with our earlier findings for younger adults. PMID- 22080934 TI - Putative CENP-B paralogues are not present at mammalian centromeres. AB - Although centromere protein B (CENP-B) is a highly conserved mammalian centromere protein, its function remains unknown. The presence of the protein is required to form artificial satellite DNA-based centromeres de novo, yet cenpb knockout mice are viable for multiple generations with no mitotic or meiotic defects, and the protein is not present at fully functional neocentromeres. Previous studies have suggested that the presence of functionally redundant paralogues of CENP-B may explain the lack of a phenotype in knockout mice, and the related Tigger-derived (TIGD) family of proteins has been implicated as the most likely candidate for such paralogues. Here, we describe an investigation of the centromere-binding properties of the three TIGD proteins most highly related to CENP-B through phylogenetic analysis through EGFP fusion studies and immunocytochemistry. Although two of the three proteins bound to human centromeres with low affinity when overexpressed as fusion proteins, the strongest candidate, TIGD3, demonstrated no native centromeric binding when using raised antibodies, either in human cells or in cenpb (-/-) mouse ES cells. We conclude that the existence of functional CENP-B paralogues is highly unlikely and that CENP-B acts alone at the centromere. Based on these data, we suggest a new, meiotic drive model of CENP-B action during centromere repositioning in evolution. PMID- 22080935 TI - Telomere-mediated truncation of barley chromosomes. AB - Engineered minichromosomes offer an enormous opportunity to plant biotechnology as they have the potential to simultaneously transfer and stably express multiple genes. Following a top-down approach, we truncated endogenous chromosomes in barley (Hordeum vulgare) by Agrobacterium-mediated transfer of T-DNA constructs containing telomere sequences. Blocks of Arabidopsis-like telomeric repeats were inserted into a binary vector suitable for stable transformation. After transfer of these constructs into immature embryos of diploid and tetraploid barley, chromosome truncation by T-DNA-induced de novo formation of telomeres could be confirmed by fluorescent in situ hybridisation, primer extension telomere repeat amplification and DNA gel blot analysis in regenerated plants. Telomere seeding connected to chromosome truncation was found in tetraploid plants only, indicating that genetic redundancy facilitates recovery of shortened chromosomes. Truncated chromosomes were transmissible in sexual reproduction, but were inherited at rates lower than expected according to Mendelian rules. PMID- 22080936 TI - Experimental investigation of beam heating in a soft X-ray scanning transmission X-ray microscope. AB - A variable temperature sample holder with an operational range of 15 to 200 degrees C and an accuracy of +/-1 degrees C has been fabricated for scanning transmission X-ray microscopes (STXM). Here we describe the device, and use it to image the polycrystalline morphology of solid stearic acid and palmitic acid at temperatures near their respective melting points as a means of checking for possible sample heating caused by the focused X-ray beam. The melting points observed in STXM were identical to those observed by conventional methods within measurement uncertainty, even under the most extreme, high dose rate imaging conditions investigated. The beam-induced temperature rise in the sample is inferred to be below 1 degrees C for dose rates of up to 2.7 GGy/s. PMID- 22080937 TI - Abundance and sources of hydrophilic and hydrophobic water-soluble organic carbon at an urban site in Korea in summer. AB - In this study, the characteristics of total water-soluble organic carbon (WSOC) and isolated WSOC fractions were examined to gain a better understanding of the pathway of organic aerosol production. 24 h PM(2.5) samples were collected during the summer (July 28-August 28, 2009) at an urban site in Korea. A glass column filled with XAD7HP resin was used to separate the filtered extracts into hydrophilic (WSOC(HPI)) and hydrophobic (WSOC(HPO)) fractions. The origins of air mass pathways arriving at the sampling site were mostly classified into three types, those originating over the East Sea of Korea that passed over the eastern inland urban and industrial regions (type I); those from the marine (western/southwestern/southern marine) and passed over the national industrial complex regions (type II); and those from northeastern China that passed through North Korea and metropolitan areas of South Korea (type III). Measurements showed an increase in the average WSOC fraction of total OC from the type II to III air mass (53 to 64%) periods. Also, higher SO(4)(2-)/SO(x) (=SO(2) + SO(4)(2-)) was observed in the type III air mass (0.70) than those in the types I (0.49) and II (0.43). According to the average values of WSOC/OC and SO(4)(2-)/SO(x), measurements suggest that the aerosols collected during the type III air mass period were more aged or photo-chemically processed than those during the types I and II air mass periods. The relationship between the SO(4)(2-)/SO(x) and WSOC/OC (R(2) = 0.64) suggests that a significant fraction of the observed WSOC at the site could be formed by an oxidation process similar to SO(4)(2-) aerosols, probably the oxidation process using OH radicals, or in-cloud processing. The photochemical production of WSOC(HPO) was also observed to significantly contribute to the total OC. PMID- 22080938 TI - Co-production of biomass and metabolites by cell retention culture of Leuconostoc citreum. AB - Cell retention culture of lactic acid bacterium Leuconostoc citreum was carried out in a fermentor equipped with an internal ceramic filtration system to co produce biomass and metabolites. The filtration system was composed of porous ceramic filter module with pore size of 0.1 MUm and total surface area of 330 cm(2). High cell density cultivation of L. citreum was achieved within the fermentor, while extracellular metabolites such as mannitol and D-lactic acid were produced through the filter with high productivities. In batch culture of L. citreum using a medium containing 50 g/L of glucose and 100 g/L of fructose, the maximum optical density (OD) monitored at 660 nm was 13 with 65 g/L of mannitol and 38 g/L of lactic acid. In cell retention culture of L. citreum with dilution rate of 0.07 h(-1), OD increased to 75, which was 6 times higher than that in batch culture. The concentrations of mannitol and lactic acid increased to 85 and 45 g/L, respectively, and were maintained throughout the cultivation to 105 h. By increasing dilution rate to 0.13 h(-1), the productivities of mannitol and lactic acid increased to 8.5 and 4.2 g/L/h, respectively, which were 2.7 to 3 times higher than those in batch culture, suggesting that cell retention culture using internal filtration system is highly effective for co-production of useful cell biomass and various extracellular metabolites. PMID- 22080939 TI - [Sleep disordered breathing and nonsustained ventricular tachycardia in patients with chronic heart failure]. AB - BACKGROUND: Patients with chronic heart failure (CHF) have a high incidence of sleep disordered breathing (SDB). It is assumed that patients with the combination of CHF and SDB have more ventricular couplets and nonsustained ventricular tachycardia (NSVT) than patients without SDB. METHODS: In 63 patients, 49 men and 14 women with chronic heart failure (EF < 45%), all-night polysomnography and long-term-ECG were performed. Mean age was 59 +/- 15 years, mean BMI 27 +/- 5 kg/m(2). 56% had an ischemic, 44% a nonischemic heart disease. 51% had heart insufficiency classification NYHA III. RESULTS: 42 of the 63 patients (67%) had sleep disordered breathing (SDB) with an AHI >=5/h. In 24 patients (38%) SDB was central, in 18 (29%) obstructive. More patients with SDB than patients without SDB had NSVT (50% vs. 19%). Nocturnal frequency of NSVT in patients with SDB was about twice as high as the rate observed during daytime (0.48/h vs. 0.21/h). In patients without SDB there was no relevant difference between day and night (0.23/h vs. 0.21/h). AHI correlated with NSVT (r = 0.329, p < 0.01). Day/night comparison of couplets was 2.3/h vs. 1.9/h in SDB patients and 2.0/h vs. 1.6/h in patients without SDB. CONCLUSIONS: Patients with chronic heart failure have a high prevalence of SDB. The combination of CHF and SDB predisposes for nocturnal malignant ventricular arrhythmias. PMID- 22080941 TI - Postoperative calcium supplementation in patients undergoing thyroidectomy. AB - PURPOSE OF REVIEW: Postoperative hypocalcemia is one of the most common complications following thyroidectomy. This review examines recent literature on predictive factors for hypocalcemia, measurement of serum calcium and parathyroid hormone (PTH) levels, and algorithms for supplementation with calcium and/or vitamin D. RECENT FINDINGS: Risk factors for developing postthyroidectomy hypocalcemia include hyperthyroidism, vitamin D deficiency, female sex, substernal thyroid disease, and thyroid cancer, necessitating central neck lymphadenectomy. Several studies have shown that routine postoperative oral calcium and calcitriol supplementation results in lower rates of tetany. Recent studies have focused on the predictive value of intraoperative and postoperative serum PTH levels for the development of symptomatic hypocalcemia. Although the exact timing and serum levels of PTH have been variable, studies have confirmed that patients with very low postoperative PTH levels require oral calcitriol and calcium supplementation. A societal-level cost-utility analysis examining the use of routine vs. selective oral calcium and calcitriol supplementation found that routine supplementation is more cost-effective, and is associated with improved quality of life, irrespective of the surgeons' specific rates of hypocalcemia. SUMMARY: Although some clinicians favor routine supplementation postoperatively, others advocate selective supplementation, guided by postoperative PTH levels. The optimal algorithm is unknown, although a recent cost-analysis study suggests that routine supplementation may be favored at the societal level. PMID- 22080942 TI - Neuroendocrine tumors of the pancreas. AB - PURPOSE OF REVIEW: Pancreatic neuroendocrine tumors (PNETs) are rare tumors, with an incidence of one per 100, 000 individuals per year, and they account for 1-2% of all pancreatic neoplasms. PNETs are a heterogeneous group with varying clinical presentation, tumor biology and prognosis. This article reviews the current diagnostic strategy and treatment armamentarium for PNETs. Special attention is paid to recent and ongoing developments in treatment, particularly with regards to multimodality treatment and newer systemic therapies for unresectable disease. RECENT FINDINGS: There has been significant progress in the genetic understanding of hereditary syndromes in regards to PNETs, as well as in the diagnosis and treatment of resectable and nonresectable PNETs. Whereas surgical therapy remains the most advisable therapy for resectable neuroendocrine tumors of the pancreas, there have been significant recent advances in systemic therapy for those with unresectable disease. Results from recent clinical trials examining mammalian target of rapamycin inhibitors and tyrosine kinase inhibitors for unresectable disease are promising in expanding treatment options for metastatic PNETs. SUMMARY: Neuroendocrine tumors of the pancreas are a heterogeneous group of tumors with varying clinical presentation, tumor biology and prognosis. Clinicians must be aware of the variety of manifestations of this disease, as well as the role of systemic chemotherapy in treatment of unresectable disease. PMID- 22080943 TI - Current status of robotic thyroidectomy and neck dissection using a gasless transaxillary approach. AB - PURPOSE OF REVIEW: To describe refinements in surgical techniques using robotic thyroidectomy and robotic modified radical neck dissection (MRND), and to discuss the impact of such developments on thyroid cancer management, from oncological, functional, and surgical viewpoints. RECENT FINDINGS: From 2009 to present, 23 reports, including three multicenter trials, on the conduct of robotic thyroid surgery via a gasless transaxillary approach appeared. Twenty-two studies discussed robotic thyroidectomy, whereas one described robotic MRND. These clinical studies showed that robotic surgery afforded identical or superior levels of surgical radicality and oncologic safety compared to use of conventional open or endoscopic surgery in patients with thyroid carcinomas. In such patients, the clinical benefits of robotic thyroidectomy include excellent cosmetic results, reduced pain, improvement in swallowing function, and low morbidity rates. From the viewpoint of surgeons, robotic surgery shortens the surgical learning curve, and causes less musculoskeletal discomfort compared with the conduct of open or endoscopic surgery. SUMMARY: The accumulated evidence to date suggests that robotic thyroidectomy and MRND can benefit both patients and surgeons. PMID- 22080944 TI - SIRT1, metabolism and cancer. AB - PURPOSE OF REVIEW: SIRT1 impacts upon diverse cellular processes via its roles in the determination of chromatin structure, chromatin remodelling and gene expression. This review covers the recent discoveries linking SIRT1 with the regulation of mammalian metabolism and considers ways in which abnormal metabolism in disease may, in turn, impact upon SIRT1 because of SIRT1's functional dependency upon NAD. RECENT FINDINGS: Diverse signalling pathways are integrated to regulate energy metabolism and homeostasis. Such pathways involve intracellular networks and mitochondria, and also intercellular signalling within and between tissues to co-ordinate adaptive metabolic responses within the organism as a whole. Here, we outline the recent studies exploring the regulatory links between SIRT1 and mitochondrial biogenesis, cellular redox and associated metabolic pathways, and angiogenesis/Notch signalling. These links are effected by the SIRT1-mediated deacetylation of transcriptional regulators and enzymes with key roles in metabolism. SUMMARY: SIRT1 activity is directly coupled with homeostasis and metabolism. SIRT1 is also a metabolic sensor. It follows that disease-related metabolic abnormalities are likely to impinge upon SIRT1 functioning. Disease-related functions of SIRT1, in their turn, offer potential targets for the development of novel SIRT1-based therapies. In cancer, for example, the survival function of SIRT1 may reflect abnormal cancer metabolism and identifies SIRT1 as a target for anticancer therapy. PMID- 22080945 TI - Altered cancer cell metabolism in gliomas with mutant IDH1 or IDH2. AB - PURPOSE OF REVIEW: IDH1/2 mutations occur in up to 70% of low-grade gliomas and secondary glioblastomas. Mutation of these enzymes reduces the wildtype function of the enzyme (conversion of isocitrate to alpha-ketoglutarate) while conferring a new enzymatic function, the production of D-2-hydroxyglutarate (D-2-HG) from alpha-ketoglutarate (alpha-KG). However, it is unclear how these enzymatic changes contribute to tumorigenesis. Here, we discuss the recent studies that demonstrate how IDH1/2 mutation may alter the metabolism and epigenome of gliomas, how these changes may contribute to tumor formation, and opportunities they might provide for molecular targeting. RECENT FINDINGS: Metabolomic studies of IDH1/2 mutant cells have revealed alterations in glutamine, fatty acid, and citrate synthesis pathways. Additionally, D-2-HG produced by IDH1/2 mutant cells can competitively inhibit alpha-KG-dependent enzymes, including histone demethylases and DNA hydroxylases, potentially leading to a distinct epigenetic phenotype. Alterations in metabolism and DNA methylation present possible mechanisms of tumorigenesis. SUMMARY: Recent attempts to improve outcomes for glioma patients have resulted in incremental gains. Studies of IDH1/2 mutations have provided mechanistic insights into tumorigenesis and potential avenues for therapeutic intervention. Further study of IDH1/2 mutations might allow for improved therapeutic strategies. PMID- 22080946 TI - Advances in robotic adrenalectomy. AB - PURPOSE OF REVIEW: We review the development of robotic adrenalectomy over the last decade, focusing on specific technical advances in the last 18 months. RECENT FINDINGS: The learning curve for robotic adrenalectomy, after which conversion rates and operative times significantly decrease, is more than 20 cases even in surgeons with extensive laparoscopic experience. Two new uses of the robot to extend traditional laparoscopic adrenalectomy have been highlighted in recent studies. Posterior retroperitoneoscopic adrenalectomy can be aided by robotic assistance, particularly in patients whose adrenal gland is located well superior to the 12th rib, on the anterior surface of the kidney, or in the renal hilum. Robotic assistance has also enabled cortical-sparing adrenalectomy which may obviate the need for steroid hormone replacement in patients with multiple or bilateral tumors. SUMMARY: Robot-assisted adrenalectomy can extend the capabilities of traditional laparoscopy, particularly in regard to performing posterior retroperitoneal and subtotal adrenalectomies. PMID- 22080948 TI - Two populations of X-ray pulsars produced by two types of supernova. AB - Two types of supernova are thought to produce the overwhelming majority of neutron stars in the Universe. The first type, iron-core-collapse supernovae, occurs when a high-mass star develops a degenerate iron core that exceeds the Chandrasekhar limit. The second type, electron-capture supernovae, is associated with the collapse of a lower-mass oxygen-neon-magnesium core as it loses pressure support owing to the sudden capture of electrons by neon and/or magnesium nuclei. It has hitherto been impossible to identify the two distinct families of neutron stars produced in these formation channels. Here we report that a large, well known class of neutron-star-hosting X-ray pulsars is actually composed of two distinct subpopulations with different characteristic spin periods, orbital periods and orbital eccentricities. This class, the Be/X-ray binaries, contains neutron stars that accrete material from a more massive companion star. The two subpopulations are most probably associated with the two distinct types of neutron-star-forming supernova, with electron-capture supernovae preferentially producing systems with short spin periods, short orbital periods and low eccentricities. Intriguingly, the split between the two subpopulations is clearest in the distribution of the logarithm of spin period, a result that had not been predicted and which still remains to be explained. PMID- 22080947 TI - Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. AB - Upon the aberrant activation of oncogenes, normal cells can enter the cellular senescence program, a state of stable cell-cycle arrest, which represents an important barrier against tumour development in vivo. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it was reported that this 'secretory phenotype' can have pro- as well as anti tumorigenic effects. Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo. Pre-malignant senescent hepatocytes secrete chemo- and cytokines and are subject to immune-mediated clearance (designated as 'senescence surveillance'), which depends on an intact CD4(+) T cell-mediated adaptive immune response. Impaired immune surveillance of pre malignant senescent hepatocytes results in the development of murine hepatocellular carcinomas (HCCs), thus showing that senescence surveillance is important for tumour suppression in vivo. In accordance with these observations, ras-specific Th1 lymphocytes could be detected in mice, in which oncogene-induced senescence had been triggered by hepatic expression of Nras(G12V). We also found that CD4(+) T cells require monocytes/macrophages to execute the clearance of senescent hepatocytes. Our study indicates that senescence surveillance represents an important extrinsic component of the senescence anti-tumour barrier, and illustrates how the cellular senescence program is involved in tumour immune surveillance by mounting specific immune responses against antigens expressed in pre-malignant senescent cells. PMID- 22080949 TI - Energetics and the evolution of human brain size. AB - The human brain stands out among mammals by being unusually large. The expensive tissue hypothesis explains its evolution by proposing a trade-off between the size of the brain and that of the digestive tract, which is smaller than expected for a primate of our body size. Although this hypothesis is widely accepted, empirical support so far has been equivocal. Here we test it in a sample of 100 mammalian species, including 23 primates, by analysing brain size and organ mass data. We found that, controlling for fat-free body mass, brain size is not negatively correlated with the mass of the digestive tract or any other expensive organ, thus refuting the expensive-tissue hypothesis. Nonetheless, consistent with the existence of energy trade-offs with brain size, we find that the size of brains and adipose depots are negatively correlated in mammals, indicating that encephalization and fat storage are compensatory strategies to buffer against starvation. However, these two strategies can be combined if fat storage does not unduly hamper locomotor efficiency. We propose that human encephalization was made possible by a combination of stabilization of energy inputs and a redirection of energy from locomotion, growth and reproduction. PMID- 22080950 TI - A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. AB - So far, two genes associated with familial melanoma have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases, and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds. Here we report the whole-genome sequencing of probands from several melanoma families, which we performed in order to identify other genes associated with familial melanoma. We identify one individual carrying a novel germline variant (coding DNA sequence c.G1075A; protein sequence p.E318K; rs149617956) in the melanoma lineage-specific oncogene microphthalmia-associated transcription factor (MITF). Although the variant co-segregated with melanoma in some but not all cases in the family, linkage analysis of 31 families subsequently identified to carry the variant generated a log of odds (lod) score of 2.7 under a dominant model, indicating E318K as a possible intermediate risk variant. Consistent with this, the E318K variant was significantly associated with melanoma in a large Australian case-control sample. Likewise, it was similarly associated in an independent case-control sample from the United Kingdom. In the Australian sample, the variant allele was significantly over-represented in cases with a family history of melanoma, multiple primary melanomas, or both. The variant allele was also associated with increased naevus count and non-blue eye colour. Functional analysis of E318K showed that MITF encoded by the variant allele had impaired sumoylation and differentially regulated several MITF targets. These data indicate that MITF is a melanoma-predisposition gene and highlight the utility of whole-genome sequencing to identify novel rare variants associated with disease susceptibility. PMID- 22080951 TI - Regulatory evolution through divergence of a phosphoswitch in the transcription factor CEBPB. AB - There is an emerging consensus that gene regulation evolves through changes in cis-regulatory elements and transcription factors. Although it is clear how nucleotide substitutions in cis-regulatory elements affect gene expression, it is not clear how amino-acid substitutions in transcription factors influence gene regulation. Here we show that amino-acid changes in the transcription factor CCAAT/enhancer binding protein-beta (CEBPB, also known as C/EBP-beta) in the stem lineage of placental mammals changed the way it responds to cyclic AMP/protein kinase A (cAMP/PKA) signalling. By functionally analysing resurrected ancestral proteins, we identify three amino-acid substitutions in an internal regulatory domain of CEBPB that are responsible for the novel function. These amino-acid substitutions reorganize the location of key phosphorylation sites, introducing a new site and removing two ancestral sites, reversing the response of CEBPB to GSK 3beta-mediated phosphorylation from repression to activation. We conclude that changing the response of transcription factors to signalling pathways can be an important mechanism of gene regulatory evolution. PMID- 22080952 TI - Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. AB - Erythrocyte invasion by Plasmodium falciparum is central to the pathogenesis of malaria. Invasion requires a series of extracellular recognition events between erythrocyte receptors and ligands on the merozoite, the invasive form of the parasite. None of the few known receptor-ligand interactions involved are required in all parasite strains, indicating that the parasite is able to access multiple redundant invasion pathways. Here, we show that we have identified a receptor-ligand pair that is essential for erythrocyte invasion in all tested P. falciparum strains. By systematically screening a library of erythrocyte proteins, we have found that the Ok blood group antigen, basigin, is a receptor for PfRh5, a parasite ligand that is essential for blood stage growth. Erythrocyte invasion was potently inhibited by soluble basigin or by basigin knockdown, and invasion could be completely blocked using low concentrations of anti-basigin antibodies; importantly, these effects were observed across all laboratory-adapted and field strains tested. Furthermore, Ok(a-) erythrocytes, which express a basigin variant that has a weaker binding affinity for PfRh5, had reduced invasion efficiencies. Our discovery of a cross-strain dependency on a single extracellular receptor-ligand pair for erythrocyte invasion by P. falciparum provides a focus for new anti-malarial therapies. PMID- 22080953 TI - Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules. AB - While patrolling the body in search of foreign antigens, naive lymphocytes continuously circulate from the blood, through the lymph nodes, into the lymphatic vessels and back to the blood. This process, called lymphocyte recirculation, provides the body with effective immune surveillance for foreign invaders and for alterations to the body's own cells. However, the mechanisms that regulate lymphocyte recirculation during homeostasis remain incompletely characterized. Here we show that dendritic cells (DCs), which are well known for their role in antigen presentation to T lymphocytes, control the entry of naive lymphocytes to lymph nodes by modulating the phenotype of high endothelial venules (HEVs), which are blood vessels specialized in lymphocyte recruitment. We found that in vivo depletion of CD11c(+) DCs in adult mice over a 1-week period induces a reduction in the size and cellularity of the peripheral and mucosal lymph nodes. In the absence of DCs, the mature adult HEV phenotype reverts to an immature neonatal phenotype, and HEV-mediated lymphocyte recruitment to lymph nodes is inhibited. Co-culture experiments showed that the effect of DCs on HEV endothelial cells is direct and requires lymphotoxin-beta-receptor-dependent signalling. DCs express lymphotoxin, and DC-derived lymphotoxin is important for lymphocyte homing to lymph nodes in vivo. Together, our results reveal a previously unsuspected role for DCs in the regulation of lymphocyte recirculation during immune surveillance. PMID- 22080954 TI - The circadian molecular clock creates epidermal stem cell heterogeneity. AB - Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis. PMID- 22080955 TI - Structure of full-length Drosophila cryptochrome. AB - The cryptochrome/photolyase (CRY/PL) family of photoreceptors mediates adaptive responses to ultraviolet and blue light exposure in all kingdoms of life. Whereas PLs function predominantly in DNA repair of cyclobutane pyrimidine dimers (CPDs) and 6-4 photolesions caused by ultraviolet radiation, CRYs transduce signals important for growth, development, magnetosensitivity and circadian clocks. Despite these diverse functions, PLs/CRYs preserve a common structural fold, a dependence on flavin adenine dinucleotide (FAD) and an internal photoactivation mechanism. However, members of the CRY/PL family differ in the substrates recognized (protein or DNA), photochemical reactions catalysed and involvement of an antenna cofactor. It is largely unknown how the animal CRYs that regulate circadian rhythms act on their substrates. CRYs contain a variable carboxy terminal tail that appends the conserved PL homology domain (PHD) and is important for function. Here, we report a 2.3-A resolution crystal structure of Drosophila CRY with an intact C terminus. The C-terminal helix docks in the analogous groove that binds DNA substrates in PLs. Conserved Trp 536 juts into the CRY catalytic centre to mimic PL recognition of DNA photolesions. The FAD anionic semiquinone found in the crystals assumes a conformation to facilitate restructuring of the tail helix. These results help reconcile the diverse functions of the CRY/PL family by demonstrating how conserved protein architecture and photochemistry can be elaborated into a range of light-driven functions. PMID- 22080956 TI - Neuronal filtering of multiplexed odour representations. AB - Neuronal activity patterns contain information in their temporal structure, indicating that information transfer between neurons may be optimized by temporal filtering. In the zebrafish olfactory bulb, subsets of output neurons (mitral cells) engage in synchronized oscillations during odour responses, but information about odour identity is contained mostly in non-oscillatory firing rate patterns. Using optogenetic manipulations and odour stimulation, we found that firing rate responses of neurons in the posterior zone of the dorsal telencephalon (Dp), a target area homologous to olfactory cortex, were largely insensitive to oscillatory synchrony of mitral cells because passive membrane properties and synaptic currents act as low-pass filters. Nevertheless, synchrony influenced spike timing. Moreover, Dp neurons responded primarily during the decorrelated steady state of mitral cell activity patterns. Temporal filtering therefore tunes Dp neurons to components of mitral cell activity patterns that are particularly informative about precise odour identity. These results demonstrate how temporal filtering can extract specific information from multiplexed neuronal codes. PMID- 22080957 TI - Self-formation of functional adenohypophysis in three-dimensional culture. AB - The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke's pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self organization of Rathke's-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions. PMID- 22080958 TI - Abusive head trauma Part II: radiological aspects. AB - Abusive head trauma (AHT) is a relatively common cause of neurotrauma in young children. Radiology plays an important role in establishing a diagnosis and assessing a prognosis. Computed tomography (CT), followed by magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI), is the best tool for neuroimaging. There is no evidence-based approach for the follow-up of AHT; both repeat CT and MRI are currently used but literature is not conclusive. A full skeletal survey according to international guidelines should always be performed to obtain information on possible underlying bone diseases or injuries suspicious for child abuse. Cranial ultrasonography is not indicated as a diagnostic modality for the evaluation of AHT. If there is a suspicion of AHT, this should be communicated with the clinicians immediately in order to arrange protective measures as long as AHT is part of the differential diagnosis. CONCLUSION: The final diagnosis of AHT can never be based on radiological findings only; this should always be made in a multidisciplinary team assessment where all clinical and psychosocial information is combined and judged by a group of experts in the field. PMID- 22080959 TI - Retinal dystrophies and gene therapy. AB - Retinal dystrophies are inherited disorders of photoreceptor and retinal pigment epithelial function that may result in severe visual impairment. Advances in molecular genetics have helped identify many of the gene defects responsible, and progress in gene transfer technology has enabled therapeutic strategies to be developed and applied. The first human clinical trials of gene therapy for RPE65 associated retinal dystrophy have shown promising initial results and have helped prepare the way for further trials of gene therapy for inherited retinal disorders. The results of these trials will provide further insight into the safety and efficacy of gene therapy for a range of currently untreatable and debilitating eye disorders. PMID- 22080960 TI - Magnetic response of conductance peak structure in junction-confined graphene nanoribbons. AB - We have numerically investigated the magnetic response of the conductance peak structures in the transport gap of graphene nanoribbons. It is shown that the magnetic field induces a number of new conductance peaks within the transport gap of graphene nanoribbons confined by structural junctions. In addition, the magnetic field causes a shift of the conductance peak position and broadening of the peak width. This behaviour is due to the disappearance of zero conductance dips at the junction as a result of breaking time-reversal symmetry. Such behaviour is, however, not observed in the electronic transport of graphene nanoribbons confined by potential barriers, i.e. p-n-junctions. Thus, the magnetic response of conductance peaks may be used to distinguish the origin of the conductance peak structure within the transport gap observed in the experiments. PMID- 22080961 TI - Duration and magnitude of hypotension and monocyte deactivation in patients with community-acquired pneumonia. AB - The objective was to examine the relationship of duration and magnitude of arterial hypotension to subsequent cellular immune suppression and cytokinemia in patients hospitalized with community-acquired pneumonia (CAP). We studied an observational cohort of 525 subjects hospitalized after presenting to the emergency department with radiographic and clinical signs of CAP. We compared the duration and magnitude of hypotension, using the cardiovascular Sequential Organ Failure Assessment (CV SOFA) subscore, to day 3 monocyte expression of human leukocyte antigen-DR (mHLA-DR), a previously validated marker of cellular immune suppression. A significant association of CV SOFA with decreased mHLA-DR expression was present in univariate analysis (P < 0.001) and persisted after adjustment for illness severity and other covariates (P = 0.01). With CV SOFA separated into components of magnitude and duration, after covariate adjustment, only duration was associated with day 3 mHLA-DR expression (P = 0.03). Levels of key proinflammatory and anti-inflammatory cytokines (interleukin 6 [IL-6], IL-10, tumor necrosis factor) increased with hypotension exposure and were also associated with mHLA-DR expression. In patients admitted with CAP, arterial hypotension over the first 3 days is associated with markers of monocyte deactivation. The duration of exposure to hypotension may be more important than the magnitude, and monocyte deactivation correlates with IL-6 and IL-10 release. These results suggest that persistent hypotension might contribute to immunosuppression following septic shock. PMID- 22080962 TI - Self-reported mammography use following BRCA1/2 genetic testing may be overestimated. AB - Adherence to mammographic screening recommendations following BRCA1/2 testing is generally assessed through self-reports. However, the validity of self-reported mammography by women who had undergone BRCA1/2 genetic testing is still unknown. This study aimed to assess the validity of self-reported mammography use in the past 12 months among women who had undergone BRCA1/2 testing. Using a self administered questionnaire, 307 women who never had cancer were asked 1 year following BRCA1/2 test result disclosure whether they undergone a mammography in the past 12 months. For each participant, this information was compared to that provided by the Quebec Health Insurance Board administrative data set for mammography claims during the same period, here considered as the gold standard. Sensitivity (Sn), specificity (Sp), predictive values, and Cohen's kappa (kappa) were calculated. The robustness of these estimates was assessed using sensitivity analysis in which we varied the administrative data time lapses up to 18 months. Overall, the agreement between self-reports and administrative data was 88% (kappa = 0.74). Among the 180 participants who had a mammography according to the administrative data, 172 adequately reported this information (Sn = 96%). Sp was moderate (76%), meaning that 24% of those who did not have a mammography reported one. Extending the time lapses to 18 months increased the Sp substantially (Sp = 90%). Self-report overestimates the use of mammography, mainly because women tend to minimize the elapsed time since their last mammography. Self-reports should be used cautiously to assess adherence to mammographic screening following BRCA1/2 testing. PMID- 22080963 TI - Preemptive dosing of plerixafor given to poor stem cell mobilizers on day 5 of G CSF administration. AB - Plerixafor, given on day 4 of G-CSF treatment is more effective than G-CSF alone in mobilizing hematopoietic progenitor cells. We tested a strategy of preemptive plerixafor use following assessment of the peak mobilization response to 5 days of G-CSF. Patients were eligible for plerixafor if, on day 5 of G-CSF, there were <7 circulating CD34+ cells/MUL or if <1.3 * 10(6) CD34+ cells/kg were collected on the first day of apheresis. Plerixafor (0.24 mg/kg s.c.) was given on day 5 of G-CSF followed by apheresis on day 6. This was repeated for up to two additional doses of plerixafor. The primary end point of the study was the percentage of patients who collected at least 2 * 10(6) CD34+ cells/kg. Twenty candidates for auto-SCT enrolled on the trial. The circulating CD34+ cell level increased a median of 3.1 fold (range 1-8 fold) after the first dose of plerixafor and a median of 1.2 fold (range 0.3-6.5 fold) after the second dose of plerixafor. In all, 15 out of 20 (75%) patients achieved the primary end point. In conclusion, the decision to administer plerixafor can be delayed until after the peak mobilization response to G-CSF has been fully assessed. PMID- 22080964 TI - Allo-SCT in a patient with CRMCC with aplastic anemia using a reduced intensity conditioning regimen. PMID- 22080965 TI - Durable complete remission after single agent decitabine in AML relapsing in extramedullary sites after allo-SCT. PMID- 22080966 TI - HLA-matched sibling stem cell transplantation in children with beta-thalassemia with anti-thymocyte globulin as part of the preparative regimen: the Greek experience. AB - BU combined with CY, the preferred preparatory regimen for thalassemic patients, is associated with a substantial incidence of graft rejection especially in patients with advanced disease stage. This study retrospectively analyzes the outcome of 75 consecutive pediatric patients with beta-thalassemia who underwent HLA-matched sibling transplantation after anti-thymocyte globulin (ATG) containing myeloablative conditioning regimens. With a median follow-up of 9 years (range 1-15 years), the overall survival (OS) and thalassemia free survival (TFS) rates were 96% and 92%, respectively. Both the estimated TRM and the cumulative incidence of rejection/failure were 4%. The cumulative incidences of acute GVHD grade II-III and grade III were 20% and 5.3%, respectively. No patient developed acute GVHD grade IV. Only two patients developed extensive chronic GVHD. The estimated OS and TFS for patients with Class 1 and 2 disease according to Pesaro criteria were 96.3% and 94.4%, whereas for patients with Class 3 disease they were 94.1% and 88.2%, respectively. In our series, the use of myeloablative conditioning regimens, which include ATG for the transplantation of thalassemic children from matched sibling donors, resulted in excellent outcomes with very low incidences of TRM and rejection. PMID- 22080967 TI - Successful treatment with plasma exchange for disseminated cidofovir-resistant adenovirus disease in a pediatric SCT recipient. PMID- 22080968 TI - Clofarabine and CY do not yield reliable engraftment of hematopoietic stem cells. PMID- 22080969 TI - Potential prolongation of PFS in mantle cell lymphoma after R-HyperCVAD: auto-SCT consolidation or rituximab maintenance. AB - We retrospectively analyzed 44 patients undergoing first-line treatment for mantle cell lymphoma with R-HyperCVAD, with or without rituximab (R) maintenance or auto-SCT. The primary study end point was PFS; secondary end point was overall survival.Median follow up for all patients was 3.3 years. Median age was 54 years, and 95% (n=42) were stage III or IV at diagnosis. In all, 17 patients underwent consolidative auto-SCT and 12 patients received R maintenance. The overall response rate was 95%, with 91% achieving complete response (CR). Median PFS for all patients was 3.5 years. Median PFS was 2.3 years for patients treated with R-HyperCVAD alone vs 3.9 years (P=0.02) with R-HyperCVAD+ R maintenance and 4.5 years (P=0.01) with R-HyperCVAD+ auto-SCT. For patients who did not achieve CR at interim staging, PFS for R-HyperCVAD alone was 1.4 years vs not reached for R-HyperCVAD+ consolidation (either R maintenance or auto-SCT) (P=0.02). PFS for patients with CR at interim staging was 3.3 years vs not reached (P=0.04) after consolidation. Our data suggest potential improvement in PFS when R-HyperCVAD is consolidated with either R maintenance or auto-SCT. This benefit appears particularly significant in those patients who do not achieve CR at interim restaging. PMID- 22080970 TI - Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation. AB - Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90 min, 5 days per week, with a median 13 treatments (range, 4 84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition. PMID- 22080972 TI - Tolerance to liver allograft after allogeneic hematopoietic cell transplantation for severe aplastic anemia from the same HLA-matched sibling donor. PMID- 22080971 TI - European data on stem cell mobilization with plerixafor in non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma patients. A subgroup analysis of the European Consortium of stem cell mobilization. AB - The effectiveness of the novel hematopoietic stem cell mobilizing agent plerixafor was evaluated in nationwide compassionate use programs in 13 European countries. A total of 580 poor mobilizers with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) were enrolled. All patients received plerixafor plus granulocyte CSF with or without chemotherapy. Overall, the collection yield was significantly higher in MM patients (>2.0 * 10(6) CD34+ cells/kg: 81.6%; >5.0 * 10(6) CD34+ cells/kg: 32.0%) than in NHL patients (>2.0 * 10(6) CD34+ cells/kg: 64.8%; >5.0 * 10(6) CD34+ cells/kg: 12.6%; P<0.0001) and also significantly higher in HL patients (>2.0 * 10(6) CD34+ cells/kg: 81.5%; >5.0 * 10(6) CD34+ cells/kg: 22.2%) than in NHL patients (P=0.013). In a subgroup analysis, there were no significant differences in mobilization success comparing patients with diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. Our data emphasize the role of plerixafor in poor mobilizers, but further strategies to improve the apheresis yield especially in patients with NHL are required. PMID- 22080973 TI - Plerixafor in AL amyloidosis: improved graft composition and faster lymphocyte recovery after auto-SCT in patient with end-stage renal-disease. PMID- 22080974 TI - The proximodistal aggravation of colitis depends on substance P released from TRPV1-expressing sensory neurons. AB - BACKGROUND: Transient receptor potential vanilloid type-1 (TRPV1)-expressing sensory neurons release neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), which play a crucial role in the pathomechanism of experimental colitis. We investigated whether innervation density and neuropeptide release were responsible for the proximodistal aggravation of murine dextran-sulfate-sodium-salt (DSS) colitis. METHODS: Whole mount TRPV1/CGRP immunostained mouse colon preparations were semiquantitatively analyzed. TRPV1 activation by capsaicin and acidic solution (pH 5.1) induced colonic CGRP/SP release, measured by EIA. Single cell quantitative PCR was employed to measure TRPV1 expression levels in DiI-labeled colonic dorsal root ganglion (DRG) neurons. The proximodistal gradient of DSS colitis severity was investigated in WT, CGRP(-/-), SP(-/-), and resiniferatoxin (RTX)-desensitized mice, employing mouse endoscopy, histology, and body weight measurement. RESULTS: TRPV1/CGRP positive nerve fiber density was increased in the distal colon wall. CGRP/SP release induced by TRPV1 activation from the distal colon was greater than that from the proximal colon. This gradient further increased in colitis. TRPV1 gene expression increased in colonic DRGs projecting to the distal, compared to that in colonic DRGs projecting to the proximal colon, and was further enhanced during colitis. In contrast to WT and CGRP(-/-) mice, SP(-/-) and RTX-desensitized mice showed amelioration of DSS colitis accompanied by a loss of the proximodistal gradient of inflammation. CONCLUSIONS: The spatial correlation among increased colonic innervation density, TRPV1 receptor expression, stimulated SP release, and colitis severity suggested that TRPV1/SP-expressing sensory neurons should be considered as a therapeutic target in human ulcerative colitis. PMID- 22080978 TI - l-carbocisteine inhibits respiratory syncytial virus infection in human tracheal epithelial cells. AB - To examine the effects of l-carbocisteine on airway infection with respiratory syncytial (RS) virus, human tracheal epithelial cells were pretreated with l carbocisteine and infected with RS virus. Viral titer, virus RNA, and pro inflammatory cytokine secretion, including interleukin (IL)-1 and IL-6, increased with time after infection. l-carbocisteine reduced the viral titer in the supernatant fluids, the amount of RS virus RNA, RS virus infection susceptibility, and the concentration of pro-inflammatory cytokines induced by virus infection. l-carbocisteine reduced the expression of intercellular adhesion molecule (ICAM)-1, an RS virus receptor, on the cells. However, l-carbocisteine had no effects on the expression of heparan sulfate, a glycosaminoglycan that binds to the RS virus attachment protein, or on the amount of intracellular activated-RhoA, isoform A of the Ras-homologous family, that binds to the RS virus fusion protein. These findings suggest that l-carbocisteine may inhibit RS virus infection by reducing the expression of ICAM-1. It may also modulate airway inflammation during RS virus infection. PMID- 22080979 TI - Real-time monitoring of blood carbon dioxide tension by fluorosensor. AB - A new intravascular fluorosensor was developed and validated for inline P(CO)2monitoring. The P(CO)2sensor was based on the fluorescent indicator 1 hydroxypyrene-3,6,8-trisulfonate. The P(CO)2sensor was then immersed in various solutions in vitro and carotid artery bypass of rabbits in vivo for testing. Changes of P(CO)2in solutions and blood were created by bubbling CO2/N2 and hyperventilation/hypoventilation, respectively. The changes of fluorescent intensity over P(CO)2 range of 14-150 mmHg was linear. The resolution of the whole sensor system was 1 mmHg, with a bias +/- SD of -0.1 +/- 2.9 mmHg and precision +/- SD of 2.1 +/- 1.9 mmHg. The sensor signal has been stable during measurement for at least 25h and was insensitive to fluctuations of ions concentration and osmosis at pathophysiological limits. The performance of the sensor is in agreement with blood gas analyzer in a wide range of P(CO)2and it is qualified for continuous intravascular measurement of blood P(CO)2at various conditions. PMID- 22080976 TI - Antioxidant therapies in traumatic brain and spinal cord injury. AB - Free radical formation and oxidative damage have been extensively investigated and validated as important contributors to the pathophysiology of acute central nervous system injury. The generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following injury occurring within minutes of mechanical impact. A key component in this event is peroxynitrite-induced lipid peroxidation. As discussed in this review, peroxynitrite formation and lipid peroxidation irreversibly damages neuronal membrane lipids and protein function, which results in subsequent disruptions in ion homeostasis, glutamate-mediated excitotoxicity, mitochondrial respiratory failure and microvascular damage. Antioxidant approaches include the inhibition and/or scavenging of superoxide, peroxynitrite, or carbonyl compounds, the inhibition of lipid peroxidation and the targeting of the endogenous antioxidant defense system. This review covers the preclinical and clinical literature supporting the role of ROS and RNS and their derived oxygen free radicals in the secondary injury response following acute traumatic brain injury (TBI) and spinal cord injury (SCI) and reviews the past and current trends in the development of antioxidant therapeutic strategies. Combinatorial treatment with the suggested mechanistically complementary antioxidants will also be discussed as a promising neuroprotective approach in TBI and SCI therapeutic research. This article is part of a Special Issue entitled: Antioxidants and antioxidant treatment in disease. PMID- 22080980 TI - Proteomes of hard and soft near-isogenic wheat lines reveal that kernel hardness is related to the amplification of a stress response during endosperm development. AB - Wheat kernel texture, a major trait determining the end-use quality of wheat flour, is mainly influenced by puroindolines. These small basic proteins display in vitro lipid binding and antimicrobial properties, but their cellular functions during grain development remain unknown. To gain an insight into their biological function, a comparative proteome analysis of two near-isogenic lines (NILs) of bread wheat Triticum aestivum L. cv. Falcon differing in the presence or absence of the puroindoline-a gene (Pina) and kernel hardness, was performed. Proteomes of the two NILs were compared at four developmental stages of the grain for the metabolic albumin/globulin fraction and the Triton-extracted amphiphilic fraction. Proteome variations showed that, during grain development, folding proteins and stress-related proteins were more abundant in the hard line compared with the soft one. These results, taken together with ultrastructural observations showing that the formation of the protein matrix occurred earlier in the hard line, suggested that a stress response, possibly the unfolded protein response, is induced earlier in the hard NIL than in the soft one leading to earlier endosperm cell death. Quantification of the albumin/globulin fraction and amphiphilic proteins at each developmental stage strengthened this hypothesis as a plateau was revealed from the 500 degrees Cd stage in the hard NIL whereas synthesis continued in the soft one. These results open new avenues concerning the function of puroindolines which could be involved in the storage protein folding machinery, consequently affecting the development of wheat endosperm and the formation of the protein matrix. PMID- 22080977 TI - Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington's disease. AB - Huntington's disease (HD) is a progressive, fatal neurodegenerative disease caused by expanded polyglutamine repeats in the HD gene. HD is characterized by chorea, seizures, involuntary movements, dystonia, cognitive decline, intellectual impairment and emotional disturbances. Research into mutant huntingtin (Htt) and mitochondria has found that mutant Htt interacts with the mitochondrial protein dynamin-related protein 1 (Drp1), enhances GTPase Drp1 enzymatic activity, and causes excessive mitochondrial fragmentation and abnormal distribution, leading to defective axonal transport of mitochondria and selective synaptic degeneration. This article summarizes latest developments in HD research and focuses on the role of abnormal mitochondrial dynamics and defective axonal transport in HD neurons. This article also discusses the therapeutic strategies that decrease mitochondrial fragmentation and neuronal damage in HD. PMID- 22080982 TI - The brave new world of antiplatelet therapy: seeking clarity in a world of increasing choice and complexity. PMID- 22080981 TI - Identification and genetic characterization of a gibberellin 2-oxidase gene that controls tree stature and reproductive growth in plum. AB - Several dwarf plum genotypes (Prunus salicina L.), due to deficiency of unknown gibberellin (GA) signalling, were identified. A cDNA encoding GA 2-oxidase (PslGA2ox), the major gibberellin catabolic enzyme in plants, was cloned and used to screen the GA-deficient hybrids. This resulted in the identification of a dwarf plum hybrid, designated as DGO24, that exhibits a markedly elevated PslGA2ox signal. Grafting 'Early Golden' (EG), a commercial plum cultivar, on DGO24 (EG/D) enhanced PslGA2ox accumulation in the scion part and generated trees of compact stature. Assessment of active GAs in such trees revealed that DGO24 and EG/D accumulated relatively much lower quantities of main bioactive GAs (GA(1) and GA(4)) than control trees (EG/M). Moreover, the physiological function of PslGA2ox was studied by determining the molecular and developmental consequences due to ectopic expression in Arabidopsis. Among several lines, two groups of homozygous transgenics that exhibited contrasting phenotypes were identified. Group-1 displayed a dwarf growth pattern typical of mutants with a GA deficiency including smaller leaves, shorter stems, and delay in the development of reproductive events. In contrast, Group-2 exhibited a 'GA overdose' phenotype as all the plants showed elongated growth, a typical response to GA application, even under limited GA conditions, potentially due to co-suppression of closely related Arabidopsis homologous. The studies reveal the possibility of utilizing PslGA2ox as a marker for developing size-controlling rootstocks in Prunus. PMID- 22080983 TI - Latest clinical data on testing for high on-treatment platelet reactivity. AB - Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes and in those who are undergoing percutaneous coronary intervention (PCI). Clopidogrel, a second-generation thienopyridine antiplatelet agent, is currently used to prevent vascular complications in atherothrombotic patients, to prevent stent thrombosis in patients undergoing PCI, and in the long term prevention of cardiovascular and cerebrovascular events. Unfortunately, despite treatment with clopidogrel, some patients continue to have cardiovascular events. This may be due in part to a suboptimal response to the drug, with minimal inhibition of platelet aggregation and/or high on-treatment platelet reactivity. Point-of-care testing of clopidogrel response, together with a reliable diagnostic cutoff, can identify patients with high on-treatment platelet reactivity and optimize their clinical management. This article reviews the impact of poor clopidogrel responsiveness on clinical outcomes, the major clinical studies using VerifyNow P2Y12 Assay(r) (Accumetrics, San Diego, CA) to assess on-clopidogrel platelet reactivity, and efforts to determine a reliable cutoff. PMID- 22080984 TI - Optimizing antiplatelet therapy following percutaneous coronary intervention: clinical pathways for platelet function testing. AB - Current guidelines recommend dual antiplatelet therapy (DAPT), which includes aspirin and a platelet P2Y(12) adenosine diphosphate (ADP) receptor antagonist, for treatment of patients with acute coronary syndrome and following percutaneous coronary intervention (PCI). Although DAPT significantly reduces stent thrombosis and major adverse cardiovascular events (MACE), there is considerable interindividual variability in the degree of platelet inhibition achieved with the most widely used ADP receptor antagonist, clopidogrel, and high on-treatment platelet activity in the setting of clopidogrel therapy (hyporesponsiveness) is associated with increased adverse cardiovascular events following PCI. Personalized tailoring of antiplatelet therapy guided by patient management algorithms and/or platelet function testing has the potential to reduce MACE and stent thrombosis. This article outlines specific algorithms for using potent new antiplatelet agents, such as prasugrel and ticagrelor, and platelet function "test and treat-to-target" strategies to reduce adverse cardiovascular events following PCI. PMID- 22080985 TI - Platelet function testing in practice: a case study. AB - Dual antiplatelet therapy with aspirin and a thienopyridine reduces ischemic cardiovascular events following percutaneous coronary intervention. However, despite this treatment, residual risk of ischemic events persists. Among other factors, enhanced platelet reactivity after thienopyridine therapy is associated with an increased risk of ischemic cardiovascular events. A heterogeneous and variable patient response to the thienopyridine clopidogrel exists and has been attributed to a number of genetic, pharmacologic, and clinical factors. Developments in point-of-care platelet function testing allow for the assessment of on-treatment platelet reactivity after thienopyridine therapy and thus identify poor responders. We report two cases of stent thrombosis in which the bedside rapid platelet function VerifyNow P2Y12 Assay(r) (Accumetrics, San Diego, CA) was used to determine on-treatment platelet reactivity and identify potential etiologies of the thrombotic events. PMID- 22080986 TI - Current options in oral antiplatelet strategies during percutaneous coronary interventions. AB - Dual antiplatelet therapy (DAPT) with aspirin and a P2Y(12) receptor blocker is the standard of care to prevent recurrent ischemic event occurrence in patients undergoing percutaneous intervention. Glycoprotein IIb/IIIa receptor inhibitors are used in addition to DAPT in the highest-risk clinical settings. The persistent occurrence of ischemic events in the presence of DAPT and the irrefutable demonstration of clopidogrel response variability are two potent arguments against the widely practiced nonselective or "one-size-fits-all" strategy of administering clopidogrel therapy and provides a strong rationale for monitoring clopidogrel therapy. New, potent P2Y(12) inhibitors such as prasugrel and ticagrelor are associated with greater platelet inhibition, faster onset of action, and better overall clinical outcomes compared with clopidogrel, but are associated with more non-surgery-related bleeding than clopidogrel. The inhibition of the platelet thrombin receptor may provide additional benefits in attenuating ischemic event occurrence in selected high-risk patients treated with DAPT. PMID- 22080987 TI - Antiplatelet therapy, cardiac surgery, and the risk of bleeding: the surgeon's perspective. AB - Antiplatelet therapy is widely accepted in the contemporary management of patients with coronary syndromes. Effective platelet inhibition can cause an increased risk of bleeding, which is more evident when patients are referred to surgical coronary revascularization. The cardiac surgeon should be familiar with all new antiplatelet drugs. In this article we compile the latest information about antiplatelet therapy and its impact on cardiac surgery. PMID- 22080988 TI - Correlation between transcranial motor and somatosensory-evoked potential findings in cervical myelopathy or radiculopathy during cervical spine surgery. AB - BACKGROUND: The correlation between electrophysiological recordings, MR images, and physical findings in cervical stenosis and cervical myelopathy are still open to debate. The goal of this study was to determine sensitivity of motor-evoked potential (MEP) and somatosensory-evoked potential (SSEP) in detecting cervical myelopathy and its correlates with the MRI findings in patients undergoing cervical spine surgeries. METHOD: Transcranial motor-evoked potentials (TcMEPs) and SSEPs were performed intraoperatively in 100 patients. The 'baseline' recordings of TcMEPs and SSEPs were correlated with patient's physical findings as well as the MR images. RESULTS: Posterior tibial and median nerves' scalp SSEP latencies were increased in myelopathic patients compared to the radiculopathy group. MEPs recorded from distal muscles such as abductor pollicis brevis and adductor hallucis (AH) muscles were more likely to be absent in myelopathic patients compared with the patients with only radiculopathy. The myelopathic patients were more likely to have no response (NR) for the lower extremity SSEP test compared with radiculopathy patients. CONCLUSION: MEP shows more sensitivity toward detecting myelopathy which is correlated well with abnormal MR images. PMID- 22080989 TI - Chronic stress enhances calcium mobilization and glutamate exocytosis in cerebrocortical synaptosomes from mice. AB - OBJECTIVES: Our previous study showed that acute restraint stress enhances depolarization-induced increases in intrasynaptosomal free calcium (Ca(2+)) concentration ([Ca(2+)](i)) and Ca(2+)-dependent glutamate release in mouse cerebrocortical nerve terminals (synaptosomes). In the present study, we investigated the effects of chronic stress on [Ca(2+)](i) and glutamate release in cerebrocortical synaptosomes from mice. METHODS: Male ddY strain mice were randomly assigned to one of two experimental groups: control group and chronic stressed group. Mice in the chronic stressed group were subjected to immobilization stress for 2 hours daily for a period of 21 days. [Ca(2+)](i) and glutamate release in cerebrocortical synaptosomes isolated from the mice were determined by fura-2 fluorescence assay and enzyme-linked fluorometric assay, respectively. RESULTS: Chronic stress caused a significant increase in resting [Ca(2+)](i) and significantly enhanced the ability of the depolarizing agents K(+) and 4-aminopyridine (4-AP) to increase [Ca(2+)](i). It also brought about a significant increase in spontaneous (unstimulated) glutamate release and significantly enhanced K(+)- and 4-AP-evoked Ca(2+)-dependent glutamate release. Synaptosomes were more sensitive to the depolarizing agents at lower concentrations following chronic stress than after acute stress. The pretreatment of synaptosomes with a combination of omega-agatoxin IVA (a P-type Ca(2+) channel blocker) and omega-conotoxin GVIA (an N-type Ca(2+) channel blocker) completely suppressed the enhancements of [Ca(2+)](i) and Ca(2+)-dependent glutamate release in chronic stressed mice. DISCUSSION: These results indicate that chronic stress enhances depolarization-evoked glutamate release by increasing [Ca(2+)](i) via stimulation of Ca(2+) entry through P- and N-type Ca(2+) channels, and that chronic stress increases the sensitivity to depolarizing agents. PMID- 22080990 TI - EEG non-linear feature extraction using correlation dimension and Hurst exponent. AB - In this work, we evaluated the differences between epileptic electroencephalogram (EEG) and interictal EEG by computing some non-linear features. Correlation dimension (CD) and Hurst exponent (H) were calculated for 100 segments of epileptic EEG and 100 segments of interictal EEG. A comparison was made between epileptic EEG and interictal EEG in those non-linear parameters. Results show that the mean values of CD are 2.64 for epileptic EEG and 4.55 for interictal EEG. We also calculated approximate entropy (ApEn) of those EEG signals. The mean values of ApEn are 0.90 for epileptic EEG and 4.55 for interictal EEG. The values of CD and ApEn of epileptic EEG are generally lower than those of interictal EEG, indicating less complexity of EEG signals during seizures. The mean values of Hurst exponent are 0.19 for epileptic EEG and 0.29 for interictal EEG. Hurst exponents for epileptic EEG and interictal EEG are both <0.5. This indicates that both epileptic and interictal EEGs show long-range anticorrelation. The value of Hurst exponent of epileptic EEG signals is lower than that of interictal EEG signals, showing that the degree of anticorrelation of epileptic EEG signals is larger than that of interictal EEG. Hence, the non-linear parameters such as CD and Hurst exponent can help interpret epileptic and interictal EEGs and their neurodynamics. PMID- 22080991 TI - Neuroprotective effects of mesenchymal stem cell transplantation in animal model of cerebellar degeneration. AB - BACKGROUND: The cerebellum has been considered a key structure for the processes involved in sensorimotor integration ultimately leading to motor planning and execution of coordinated movement. Thus, motor deficits and behavioral changes can be associated with cerebellar degeneration. METHODS: Here, the chemical neurotoxin pyridine-2,3-dicarboxylic acid (quinolinic acid, QA) used to create partially cerebellar degeneration in adult Wistar rats suitable for use in stem cell transplantation studies. Stereotaxicaly administration of QA (0.2 mmol) in the right cerebellar hemisphere (folia VI) caused noticeable motor disturbance in all treated animals. Forty-eights hours after causing lesion, rat bone marrow derived mesenchymal stem cells (MSCs) were transplanted into damaged cerebellar hemisphere. We investigated the role of MSC transplantation in forms of motor and non-motor learning that involves the cerebellum and its neuroprotective effects in Purkinje cells loss. RESULTS: CM-Dil labeling showed that the transplanted MSCs survived and migrated in the cerebellum 6 weeks after transplantation. The MSC-transplanted group showed markedly improved functional performance on the rotating rod test (P<=0.0001) and beam walking test (P<=0.0001) during 6 weeks compared with the controls. For non-motor learning, we used passive avoidance learning test in 3 weeks after transplantation. The results showed that MSC transplantation prevented the development of memory deficit caused by cerebellar degeneration (P<=0.001). Stereological analysis in 6 weeks after transplantation showed that QA significantly decreases Purkinje cells in vehicle-treated rats and MSC transplantation is neuroprotective and decreases Purkinje cell loss in MSC treated rats (P<=0.0001). CONCLUSION: The results indicate that transplantation of MSCs can significantly reduce the behavioral and neuroanatomical abnormalities of these animals during 6 weeks after engraftment. According to results of this assay, cell therapy by means of bone marrow-derived adult stem cells promises for treatment of cerebellar diseases. PMID- 22080992 TI - The course of dynamic cerebral autoregulation during cervical internal carotid artery occlusion. AB - OBJECTIVES: The selection of patients with cervical internal carotid artery occlusion (ICAO) for extracranial-intracranial bypass surgery is based on exhausted cerebrovascular reactivity to vasodilatory stimuli. However, a spontaneous increase in this reactivity can occur with time, questioning the ideal time for bypass surgery. In contrast, the natural course of dynamic cerebral autoregulation is not known in these patients. METHODS: Patients with cervical ICAO were examined at baseline and after a mean interval of 15 months. Dynamic autoregulation was determined by transcranial Doppler sonography in both middle cerebral arteries via respiratory-induced 0.1-Hz oscillations (phase, available for n=47 patients) and correlation analysis between diastolic blood pressure and Doppler signal (index Dx, n=55 patients). Pre-defined cut-off values and repeatability measures of healthy controls were used to define significant individual changes in autoregulation. RESULTS: Group mean comparisons between studies were not significant for any autoregulation parameter. The intraclass correlation coefficient between studies was high for phase (ipsilateral: 0.83; contralateral: 0.74), and moderate for Dx (ipsilateral: 0.63; contralateral: 0.35). There was no clear trend for an improvement across cut-off values. A significant individual improvement/deterioration in autoregulation occurred in 6%/6% for phase and 13%/9% for Dx. DISCUSSION: Dynamic autoregulation only rarely improves during the course of ICAO. This finding should be considered when deciding for or against a policy of delaying extracranial-intracranial bypass surgery for reasons of a potentially improving hemodynamic status. PMID- 22080993 TI - Luteolin reduces primary hippocampal neurons death induced by neuroinflammation. AB - OBJECTIVES: This study examined whether luteolin may exert an anti-inflammatory effect in microglia and may be neuroprotective by regulating microglia activation. METHODS: We treated BV2 microglia with 1.0 MUg/ml lipopolysaccharide (LPS) after incubation with luteolin for 1 hour, the nitric oxide (NO) levels were determined by a Griess reaction, the inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1beta) mRNA expression were determined by real-time PCR analysis, the iNOS and COX-2 protein induction were determined by Western blot analysis, and the levels of prostaglandin E(2) (PGE(2)), TNF-alpha, and IL-1beta were determined by enzyme-linked immunosorbent assay (ELISA) kits. Rat primary hippocampal neurons were co-cultured with LPS-activated BV2 microglia with 20 MUM luteolin for 24 hours, the hippocampal neurons viability was determined by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the number of apoptotic hippocampal neurons was determined by immunofluorescence detection. RESULTS: Luteolin significantly inhibited the expression of iNOS and COX-2 in LPS induced BV2 microglia. Moreover, the compound down-regulated the proinflammatory cytokines (TNF-alpha and IL-1beta) as well as the production of NO and PGE(2) in these cells. When hippocampal neurons were co-cultured with LPS-stimulated BV2 microglia, the administration of 20 MUM luteolin increased the neurons viability and reduced the number of apoptotic neurons. CONCLUSION: These data demonstrate that anti-inflammatory activity of luteolin in microglia contributes to its neuroprotective effect and suggest that it may have a potential therapeutic application in the treatment of neurodegenerative diseases. PMID- 22080994 TI - L-cysteine attenuates peroxynitrite-elicited cytotoxicity to spiral ganglion neurons: possible relation to hearing loss. AB - OBJECTIVES: The purpose of this work was to investigate whether L-cysteine was able to protect spiral ganglion neurons (SGNs) against peroxynitrite (ONOO(-)) elicited toxicity. METHODS: The rat SGNs were isolated and cultured in this work. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The morphological changes were examined under inverted phase contrast microscope. Cells underwent apoptosis were determined by TdT-mediated dUTP nick end labeling (TUNEL) assay. Intracellular glutathione (GSH) content, superoxide dismutase (SOD) activity and malonaldehyde (MDA) level were detected by biochemical methods. Laser scanning confocal microscope was employed to analyze cytosolic Ca(2+) concentration. RESULTS: Results showed that ONOO(-) reduced the cell viability of SGNs in a time- and dose-dependent manner. ONOO(-)-triggered cell damage was further confirmed via apoptotic pathway rather than necrosis. Pretreatment with L-cysteine (5 mM) for 12 hours could almost completely rescue SGNs from ONOO(-)-induced damage. The decrease in intracellular GSH content and SOD activity, as well as the increase in MDA level induced by ONOO(-) were correspondingly antagonized by the administration of L-cysteine. Furthermore, L-cysteine can significantly inhibit elevation of Ca(2+) concentration induced by ONOO(-). DISCUSSION: Our findings indicate that L-cysteine protects SGNs from ONOO(-)-induced damage via enhancing the antioxidative activity and, suppressing the lipid peroxidation as well as the release of cytosolic Ca(2+), thereby indicating that oxidation resistance was useful to prevent audiological diseases initiated by oxidative stress. PMID- 22080995 TI - Stent-assisted aneurysm coil embolization: safety and efficacy at a low-volume center. AB - BACKGROUND AND PURPOSE: To compare safety and efficacy of cerebral aneurysm embolization with and without Neuroform stent placement at a low procedural volume center. METHODS: Retrospective cohort study of unruptured aneurysm coil embolization with and without Neuroform stent assistance over a period of 53 months at a center performing 14.4 interventions per year. Neuroform stent assisted embolization was performed for 26 aneurysms in 25 patients (mean age: 61.3 years). Twelve patients (mean age: 64.3 years) with 12 unruptured aneurysms were treated without stent support. Comparative analysis of complications, angiographic findings, and clinical outcomes was performed. RESULTS: Procedural complications for the Neuroform stent group was 7.69% (2/26) versus 8.34% (1/12) for aneurysms without (P=0.7; OR: 1.1; CI: 0.09-13.35).The Modified Rankin Scale (MRS) and Glasgow Outcome Scale (GOS) scores for all patients in the stent and non-stent groups were 0 and 5, respectively. Three out of 20 aneurysms (15%) were retreated for major recurrence in the stent group and two of 10 (20%) in the non stent group (P=0.55; OR: 1.42; 95% CI: 0.20-10.23). At a mean follow-up of 16.9 months, persistent complete occlusion was observed in 36.8% (7/19) of aneurysms with stent support. At a mean of 15.9-month follow-up in 10 non-stented aneurysms, persistent complete occlusion was observed in 50% of aneurysms (P=0.69; OR=2.3; 95% CI: 0.38-14.2). CONCLUSION: Neuroform stent-assisted coil embolization at a low volume center is efficacious and does not increase procedural risk with optimal operator experience. PMID- 22080996 TI - Cerebrospinal fluid leak after microsurgical surgery in vestibular schwannomas via retrosigmoidal craniotomy. AB - OBJECTIVE: Cerebrospinal fluid (CSF) leak is still a common complication in surgery of vestibular schwannoma, increasing morbidity and prolonging hospital stay. Our single center study was performed to determine the incidences of CSF leaks after microsurgical removal of vestibular schwannoma via a retrosigmoidal approach with two different surgical closure techniques. METHODS: Between January 2003 and December 2009 in 81 patients, microsurgical tumor resection using a suboccipital, retrosigmoidal approach was performed with an interdisciplinary ENT and neurosurgical management was performed. In 41 cases, the dural closure was done using a sandwich technique: subdural closure with TissuFleece(r) respectively Spongostan(r), and after that dural suture and epidural Tachosil(r) were fixed on. In 40 cases, the dura was sealed epidurally with Tachosil after suture. In 65 cases, the posterior wall of the petrous bone was drilled. The closure was performed using muscle and FibrinGlue(r). All patients had a minimal follow-up of 1 year. RESULTS: Seven patients (8.6%) developed a CSF fistula. Three patients (3.7%) underwent surgical procedure because of persisting CSF fistula while in four cases (4.9%) spontaneous closure under lumbar drain was observed. Comparing the different techniques of dural sealing, we found in 41 patients with sandwich technique three CSF leaks (7.3%) while there were four CSF leaks (10%) in 40 patients with a single epidurally sealed dural closure (P=0.69). No rhinorrhea or otorhinorrhea was observed. No intracranial infection or meningitis in case of CSF leak occurred. CONCLUSION: Suture and occlusion of the dura is an important step to prevent CSF leak and postoperative infection. By comparing sandwich technique and single-layer dural sealing, no significant difference could be shown. PMID- 22080997 TI - Long-term antalgic effects of repetitive transcranial magnetic stimulation of motor cortex and serum beta-endorphin in patients with phantom pain. AB - OBJECTIVES: To assess the long-term analgesic effect of repetitive transcranial stimulation (rTMS) on chronic phantom pain using high frequency stimulation and to measure the serum beta-endorphin level pre- and post-rTMS. MATERIAL AND METHODS: The study included 27 patients with unilateral amputation; all patients had chronic phantom pain. The patients were classified into two groups. Seventeen patients received 10 minutes real rTMS over the hand area of motor cortex (20 Hz, 10 second trains, intensity 80% of motor threshold) every day for five consecutive days and 10 patients received sham stimulation. Pain was assessed using a visual analogue scale (VAS) and the Leeds assessment of neuropathic symptoms and signs (LANSS) scale, before and after the first, fifth sessions, one and two months after the last session. Quantitative determination of serum beta endorphin before and after five sessions was measured. RESULTS: There was no significant difference between true and sham groups in the duration of illness, VAS, LANSS scores and resting motor threshold in upper and lower limb amputation at the base line. VAS and LANS scores of the patients who received real rTMS decreased more over the course of the treatment through the different points of follow-up (after five sessions, one and two months) than those who received sham stimulation. Serum beta-endorphin was increased significantly after real stimulation with no changes in patients received shame. Serum beta-endorphin showed no significant correlation to Hamilton depression, anxiety, VAS and LANS scores in true or sham groups before or after five sessions for rTMS. CONCLUSION: These results confirm that five daily sessions of rTMS over motor cortex can produce long lasting pain relief in patients with phantom pain and it might be related to an elevation of serum beta-endorphin concentration. PMID- 22080999 TI - Hemifacial spasm caused by cross type vascular compression. AB - OBJECTIVES: The meatal segment of anterior inferior cerebellar artery usually crosses over the gap between cranial nerves VII and VIII, and may compress the cisternal portion (CP) of the facial nerve. This is defined as cross type compression, which is easy to be neglected and thus leads to poor outcome. Here our experience in treating patients of cross type hemifacial spasm (HFS) is reported. METHODS: Twenty-one patients of HFS due to cross type compression were treated with microvascular decompression (MVD) surgery with the aid of abnormal muscle response monitoring. RESULTS: In addition to cross type compression at CP, there were typical vascular compressions on the root exit zone and attached segment in 20 cases. After MVD surgery, 17 patients were cured, 3 patients achieved good resolution of spasm, and the other 1 patient got delayed resolution. Three patients had postoperative transient hearing loss and/or tinnitus. DISCUSSION: Even there are apparently typical vascular compressions at proximal portion of the facial nerve, the surgeon should be aware that cross type compression at the CP may co-exist. With the aid of abnormal muscle response (AMR) monitoring, MVD is efficient for patients due to cross type compression. PMID- 22080998 TI - Gait variability in Parkinson's disease: influence of walking speed and dopaminergic treatment. AB - OBJECTIVES: To study the effects of levodopa and walking speed on gait variability in individuals with Parkinson's disease (PD). METHODS: Thirty-three individuals with PD were studied. Their mean age was 70.61+/-9.23 year. The average time since diagnosis was 9.65+/-5.80 year. Gait variability was studied while 'OFF' and 'ON' dopaminergic medication when the subjects walked at their usual and fastest speeds. RESULTS: Variability of step time, double support time, stride length and stride velocity decreased significantly (P=0.037; P=0.037; P=0.022; P=0.043, respectively) after dopaminergic treatment. When subjects increased walking speed, the variability of stride length and stride velocity decreased significantly (P=0.038 and P=0.004, respectively) both while 'OFF' and 'ON' levodopa. Increasing walking speed did not change the variability of step time and double support time regardless of medication status. CONCLUSIONS: Levodopa decreased gait variability in persons with PD. Stride length and stride velocity variability appeared to be speed dependent parameters, whereas, the variability of step time and double support time appeared to be speed independent measures. Levodopa had positive effects on gait stability in PD. PMID- 22081000 TI - Sonographic and electrophysiological detection in patients with carpal tunnel syndrome. AB - OBJECTIVES: To assess prospectively the significance of sonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome (CTS), to look for proper parameters and cutoff values for the sonographic diagnosis, and to correlate with the electrophysiological findings. MATERIALS AND METHODS: This study involved 30 patients, who were clinically diagnosed as CTS merely based on their symptoms and signs; and 30 healthy volunteers were served as controls. Eligible subjects underwent sonographic and electromyographic detection. RESULTS: In the CTS patient group, the cross-sectional area (CSA) at the pisiform bone level (CSA2) and the diameter (D) of the median nerve increased. When the cutoff values of CSA2 and D were 0.105 cm(2) and 0.195 cm, the sensitivity, specificity and accuracy of the diagnosis were 91.5, 94.5, 94.1%, and 90.7, 80.4, 86.5%, respectively. Both CSA and D were negatively related to sensory conduction velocity, while CSA was positively related to distal motor latency. CONCLUSION: There is a good association of sonographic with electrophysiologic detection for the diagnosis of CTS. PMID- 22081001 TI - Lateralized alpha-motoneuron excitabilities during lying and standing of healthy individuals in relation to parkinsonian rigidity. AB - OBJECTIVES: To elucidate mechanisms of Parkinsonian rigidity by assessing excitability of alpha-motoneurons innervating right and left soleus muscles in healthy controls and Parkinson's disease (PD) patients with rigidities in the right, left and both legs. METHODS: One group of 45 controls was recruited and 60 PD patients in three groups: rigidities, predominantly in the right, left and both legs. H-reflex (H) and muscle response (M) were recorded from right and left soleus muscles during stimulations of the posterior tibial nerve at the popliteal fossa while lying and standing. The H/M ratio was taken as an index for motoneuron excitability. RESULTS: Mean H/M ratios were significantly different on the right and left sides, modified by postural changes in controls and PD patients. Analysis of variance showed that in healthy subjects the H/M ratio was: standing>lying (right), lying>standing (left). In right leg rigidity patients, the H/M ratio was greatest during standing, and smallest during lying. In left leg rigidity patients, the H/M ratios on the right and left sides were equally independent of posture. In controls, left H/M>right while lying, left, but =40 years of age, English speaking, cognitively intact, and having a diagnosis of stage III or IV tumor. Dyads were randomized to a nurse-delivered symptom management intervention (N = 88) versus the coach-led group (N = 81). Data were collected via telephone interviews at baseline, 10, and 16 weeks. RESULTS: There was no significant main effect of the problem-solving intervention on symptom assistance at 10 weeks, but there were two significant interactions, between trial arm and depressive symptoms and between baseline assistance with symptoms and relationship to the patient. Caregivers with lower depressive symptoms were more likely (OR = 1.99, 95% CI = 1.45-2.76) to provide assistance at 10 weeks if they received the nurse-delivered intervention. Spousal (versus non-spouses) caregivers who provided assistance at baseline were less likely to provide assistance at 10 weeks (OR = 0.58, 95% CI 0.36-0.94). No significant trial arm effects were found on caregiver emotional health, but assistance with greater number of symptoms was associated with worse caregiver depressive symptoms (p < 0.01) and burden (impact on schedule, p < 0.01). CONCLUSIONS: Findings suggest that a nurse-delivered problem-solving intervention increases family caregivers' level of assistance in symptom management for caregivers with lower levels of depressive symptoms. Data also suggest interventions focused solely on care recipient symptom management may not be effective in improving caregivers' emotional health. PMID- 22081057 TI - Evaluating adherence to recommended diets among cancer patients. AB - PURPOSE: We examined dietary and health-related behaviors among Korean cancer patients in the fourth Korean National Health and Nutrition Examination Survey. METHODS: To compare the dietary and health-related behaviors among cancer patients, patients who had recovered from cancer, and those who had never had cancer, we obtained odds ratio (OR)s and 95% confidence interval (CI)s for the adherence to American Institute for Cancer Research (AICR) recommendations or a Dietary Approaches to Stop Hypertension (DASH)-style diet using the multivariate polytomous logistic regression. RESULTS: A total of 103 cancer patients, 139 patients who had recovered from cancer, and 7,963 participants who had never had cancer were included. Patients who had ever been diagnosed with cancer were more likely to follow AICR recommendations or a DASH-style diet compared to those who had never had cancer. Compared to bottom tertile of the AICR adherence score, ORs (95% CIs) in the top tertile were 3.19 (1.86-5.46) for patients who recovered from cancer and 3.34 (1.81-6.17) for cancer patients. For a DASH-style diet, we found an OR of 2.26 (95% CI 1.28-3.99) for patients who recovered from cancer and an OR of 1.60 (95% CI 0.89-2.89) for cancer patients, comparing top to bottom tertiles. We also found that the degree of adherence among cancer patients was stronger among ever smokers than never smokers. CONCLUSIONS: Korean patients who had ever been diagnosed with cancer showed higher adherence to diets designed to prevent cancer or high blood pressure than those who had never had cancer. Our observations warrant further prospective studies to evaluate the association of adherence to a healthy diet with survival and quality of life among Asian cancer patients. PMID- 22081058 TI - Do elderly patients with metastatic cancer have worse quality of life scores? AB - PURPOSE: The purpose of this study is to compare self-reported quality of life (QOL) scores in old and young patients with metastatic cancer using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire. MATERIALS AND METHODS: Patients receiving palliative radiotherapy (RT) for bone metastases and brain metastases completed the QLQ-C15-PAL questionnaire prior to treatment. Using multiple linear regression analysis, a parametric test, the QLQ-C15-PAL scores were compared using 65 and 70 years as cutoff ages. RESULTS: A total of 340 patients were referred for palliative RT for bone metastases (n = 190) or brain metastases (n = 150). Physical functioning and appetite were worse in the older group using either 65 or 70 years as the cutoff age. Age-related differences in the QLQ-C15-PAL scores varied as a function of age cutoff used and location of metastatic site irradiated. CONCLUSION: Based on the (EORTC) QLQ-C15-PAL, elderly advanced cancer patients have a different QOL profile. Similar observations have been reported with the (EORTC) QLQ-C30 questionnaire. PMID- 22081059 TI - Children with cerebral palsy: racial disparities in functional limitations. AB - BACKGROUND: Previous studies of the frequency of cerebral palsy in the United States have found excess prevalence in black children relative to other groups. Whether the severity of cerebral palsy differs between black and white children has not previously been investigated. METHODS: A population-based surveillance system in 4 regions of the United States identified 476 children with cerebral palsy among 142,338 8-year-old children in 2006. Motor function was rated by the Gross Motor Function Classification System and grouped into 3 categories of severity. We used multiple imputation to account for missing information on motor function and calculated the race-specific prevalence of each cerebral palsy severity level. RESULTS: The prevalence of cerebral palsy was 3.7 per 1000 black children and 3.2 per 1000 white children (prevalence odds ratio [OR] = 1.2 [95% confidence interval = 1.0-1.4]). When stratified by severity of functional limitation, the racial disparity was present only for severe cerebral palsy (black vs. white prevalence OR=1.7 [1.1-2.4]). The excess prevalence of severe cerebral palsy in black children was evident in term and very preterm birth strata. CONCLUSION: Black children in the United States appear to have a higher prevalence of cerebral palsy overall than white children, although the excess prevalence of cerebral palsy in black children is seen only among those with the most severe limitations. Further research is needed to explore reasons for this disparity in functional limitations; potential mechanisms include racial differences in risk factors, access to interventions, and under-identification of mild cerebral palsy in black children. PMID- 22081060 TI - Perfluorinated compounds and subfecundity in pregnant women. AB - BACKGROUND: Perfluorinated compounds are ubiquitous pollutants; epidemiologic data suggest they may be associated with adverse health outcomes, including subfecundity. We examined subfecundity in relation to 2 perfluorinated compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). METHODS: This case-control analysis included 910 women enrolled in the Norwegian Mother and Child Cohort Study in 2003 and 2004. Around gestational week 17, women reported their time to pregnancy and provided blood samples. Cases consisted of 416 women with a time to pregnancy greater than 12 months, considered subfecund. Plasma concentrations of perfluorinated compounds were analyzed using liquid chromatography-mass spectrometry. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each pollutant quartile using logistic regression. Estimates were further stratified by parity. RESULTS: The median plasma concentration of PFOS was 13.0 ng/mL (interquartile range [IQR] = 10.3 16.6 ng/mL) and of PFOA was 2.2 ng/mL (IQR = 1.7-3.0 ng/mL). The relative odds of subfecundity among parous women was 2.1 (95% CI = 1.2-3.8) for the highest PFOS quartile and 2.1 (1.0-4.0) for the highest PFOA quartile. Among nulliparous women, the respective relative odds were 0.7 (0.4-1.3) and 0.5 (0.2-1.2). CONCLUSION: Previous studies suggest that the body burden of perfluorinated compounds decreases during pregnancy and lactation through transfer to the fetus and to breast milk. Afterward, the body burden may increase again. Among parous women, increased body burden may be due to a long interpregnancy interval rather than the cause of a long time to pregnancy. Therefore, data from nulliparous women may be more informative regarding toxic effects of perfluorinated compounds. Our results among nulliparous women did not support an association with subfecundity. PMID- 22081061 TI - Radon and skin cancer in southwest England: an ecologic study. AB - BACKGROUND: Radon, a naturally occurring radioactive gas, is a carcinogen that causes a small proportion of lung cancers among exposed populations. Theoretical models suggest that radon may also be a risk factor for skin cancer, but epidemiologic evidence for this relationship is weak. In this study, we investigated ecologic associations between environmental radon concentration and the incidence of various types of skin cancer. METHODS: We analyzed data for 287 small areas (postcode sectors) in southwest England for the years 2000-2004. Poisson regression was used to compare registration rates of malignant melanoma, basal cell carcinoma, and squamous cell carcinoma across mean indoor radon concentrations from household surveys. Analyses were adjusted for potentially confounding factors, including age, sex, population socioeconomic status, and mean hours of bright sunshine. RESULTS: No association was observed between mean postcode sector radon concentration and either malignant melanoma or basal cell carcinoma registration rates. However, sectors with higher radon levels had higher squamous cell carcinoma registration rates, with evidence of an exposure response relationship. Comparing highest and lowest radon categories, postcode sectors with mean radon >= 230 Bq/m(3) had registration rates 1.76 (95% confidence interval = 1.46-2.11) times those with mean radon 0-39 Bq/m(3). Associations persisted after adjustment for potential confounders. CONCLUSIONS: This ecologic study suggests that environmental radon exposure may be a risk factor for squamous cell carcinoma. Further study is warranted to overcome ecologic design limitations and to determine whether this relationship is generalizable to national and international settings. PMID- 22081062 TI - Berkson's bias, selection bias, and missing data. AB - Although Berkson's bias is widely recognized in the epidemiologic literature, it remains underappreciated as a model of both selection bias and bias due to missing data. Simple causal diagrams and 2 * 2 tables illustrate how Berkson's bias connects to collider bias and selection bias more generally, and show the strong analogies between Berksonian selection bias and bias due to missing data. In some situations, considerations of whether data are missing at random or missing not at random are less important than the causal structure of the missing data process. Although dealing with missing data always relies on strong assumptions about unobserved variables, the intuitions built with simple examples can provide a better understanding of approaches to missing data in real-world situations. PMID- 22081064 TI - The gene encoding the melanin-concentrating hormone receptor 1 is associated with schizophrenia in a Danish case-control sample. AB - OBJECTIVE: The MCHR1 gene encoding the melanin-concentrating hormone receptor 1 is located on chromosome 22q13.2 and has previously been associated with schizophrenia in a study of cases and controls from the Faroe Islands and Scotland. Herein we report an association between variations in the MCHR1 gene and schizophrenia, based on analyses of a larger sample and an increased number of single nucleotide polymorphisms (SNPs) than used in the previous study. METHODS: Eighteen SNPs in the MCHR1 gene region were genotyped in a Caucasian case-control sample from Denmark consisting of 390 individuals with schizophrenia and 814 control individuals. Sex-specific analysis and analysis of association with antipsychotic treatment were performed. RESULTS: Five SNPs in the proximal region of MCHR1 were significantly associated with schizophrenia. The associations seemed to be sex specific, predominantly seen in men where one SNP (rs133073) remained significant (P=0.003) after correction for multiple testing. When combining the P values in the proximal region of MCHR1, the region-wise P value was low (P=0.009) supporting that variations in this part of the gene is associated with schizophrenia. Furthermore, the association was stronger in patients responding to conventional and atypical antipsychotic medication except clozapine. CONCLUSION: Our results suggest that MCHR1 may influence schizophrenia susceptibility, in particular among men and patients responding to conventional (nonclozapine) treatment. PMID- 22081063 TI - Data mining approaches for genome-wide association of mood disorders. AB - BACKGROUND: Mood disorders are highly heritable forms of major mental illness. A major breakthrough in elucidating the genetic architecture of mood disorders was anticipated with the advent of genome-wide association studies (GWAS). However, to date few susceptibility loci have been conclusively identified. The genetic etiology of mood disorders appears to be quite complex, and as a result, alternative approaches for analyzing GWAS data are needed. Recently, a polygenic scoring approach that captures the effects of alleles across multiple loci was successfully applied to the analysis of GWAS data in schizophrenia and bipolar disorder (BP). However, this method may be overly simplistic in its approach to the complexity of genetic effects. Data mining methods are available that may be applied to analyze the high dimensional data generated by GWAS of complex psychiatric disorders. RESULTS: We sought to compare the performance of five data mining methods, namely, Bayesian networks, support vector machine, random forest, radial basis function network, and logistic regression, against the polygenic scoring approach in the analysis of GWAS data on BP. The different classification methods were trained on GWAS datasets from the Bipolar Genome Study (2191 cases with BP and 1434 controls) and their ability to accurately classify case/control status was tested on a GWAS dataset from the Wellcome Trust Case Control Consortium. CONCLUSION: The performance of the classifiers in the test dataset was evaluated by comparing area under the receiver operating characteristic curves. Bayesian networks performed the best of all the data mining classifiers, but none of these did significantly better than the polygenic score approach. We further examined a subset of single-nucleotide polymorphisms (SNPs) in genes that are expressed in the brain, under the hypothesis that these might be most relevant to BP susceptibility, but all the classifiers performed worse with this reduced set of SNPs. The discriminative accuracy of all of these methods is unlikely to be of diagnostic or clinical utility at the present time. Further research is needed to develop strategies for selecting sets of SNPs likely to be relevant to disease susceptibility and to determine if other data mining classifiers that utilize other algorithms for inferring relationships among the sets of SNPs may perform better. PMID- 22081065 TI - Management of detrusor external sphincter dyssynergia in neurogenic bladder. AB - Spinal cord injury (SCI) affects 11.5 to 53.4 individuals per million of the population in developed countries each year. SCI is caused by trauma, although it can also result from myelopathy, myelitis, vascular disease or arteriovenous malformations and multiple sclerosis. Patients with complete lesions of the spinal cord between spinal cord level T6 and S2, after they recover from spinal shock, generally exhibit involuntary bladder contractions without sensation, smooth sphincter synergy, but with detrusor striated sphincter dyssynergia (DESD). Those with lesions above spinal cord level T6 may experience, in addition, smooth sphincter dyssynergia and autonomic hyperreflexia. DESD is a debilitating problem in patients with SCI. It carries a high risk of complications, and even life expectancy can be affected. Nearly half of the patients with untreated DESD will develop deleterious urologic complications, due to high intravesical pressures, resulting in urolithiasis, urinary tract infection (UTI), vesicoureteral reflux (VUR), hydronephrosis, obstructive uropathy, and renal failure. The mainstay of treatment is the use of antimuscarinics and catheterization, but in those for whom this is not possible external sphincterotomy has been a last resort option. External sphincterotomy is associated with significant risks, including haemorrhage; erectile dysfunction and the possibility of redo procedures. Over the last decade alternatives have been investigated, such as urethral stents and intrasphincteric botulinum toxin injection. In this review, we will cover neurogenic DESD, with emphasis on definition, classifications, diagnosis and different therapeutic options available. PMID- 22081066 TI - Suppression of Myc oncogenic activity by nucleostemin haploinsufficiency. AB - Nucleostemin (NS), a nucleolar GTPase, is highly expressed in stem/progenitor cells and in most cancer cells. However, little is known about the regulation of its expression. Here, we identify the NS gene as a novel direct transcriptional target of the c-Myc oncoprotein. We show that Myc overexpression enhances NS transcription in cultured cells and in pre-neoplastic B cells from EMU-myc transgenic mice. Consistent with NS being downstream of Myc, NS expression parallels that of Myc in a large panel of human cancer cell lines. Using chromatin immunoprecipitation we show that c-Myc binds to a well-conserved E-box in the NS promoter. Critically, we show NS haploinsufficiency profoundly delays Myc-induced cancer formation in vivo. NS+/-EMU-myc transgenic mice have much slower rates of B-cell lymphoma development, with life spans twice that of their wild-type littermates. Moreover, we demonstrate that NS is essential for the proliferation of Myc-overexpressing cells in cultured cells and in vivo: impaired lymphoma development was associated with a drastic decrease of c-Myc-induced proliferation of pre-tumoural B cells. Finally, we provide evidence that in cell culture NS controls cell proliferation independently of p53 and that NS haploinsufficiency significantly delays lymphomagenesis in p53-deficient mice. Together these data indicate that NS functions downstream of Myc as a rate limiting regulator of cell proliferation and transformation, independently from its putative role within the p53 pathway. Targeting NS is therefore expected to compromise early tumour development irrespectively of the p53 status. PMID- 22081067 TI - EGFR signaling upregulates expression of microsomal prostaglandin E synthase-1 in cancer cells leading to enhanced tumorigenicity. AB - In this report we describe the contribution of prostaglandin E(2) (PGE(2)) derived from the inducible microsomal PGE-synthase type-1 (mPGES-1) to the epidermal growth factor receptor (EGFR) oncogenic drive in tumor epithelial cells and in tumor-bearing mice. EGFR stimulation upregulated expression of mPGES-1 in HT-29, A431 and A549 cancer cells. Egr-1, a transcription factor induced by EGF, mediated this response. The Egr-1 rise provoked the overexpression of mPGES-1 messenger and protein, and enhanced PGE(2) formation. These changes were suppressed either by silencing Egr-1, or by upstream blockade of EGFR or ERK1/2 signals. Further, in a clonogenic assay on tumor cells, EGF induced a florid tumorigenic phenotype, which regressed when mPGES-1 was silenced or knocked down. EGF-induced mPGES-1 overexpression in epithelial cell reduced E-cadherin expression, whereas enhancing that of vimentin, suggesting an incipient mesenchymal phenotype. Additionally, inhibiting the EGFR in mice bearing the A431 tumor, the mPGES-1 expression and the tumor growth, exhibited a parallel decline. In conclusion, these findings provide novel evidence that a tight cooperation between the EGF/EGFR and mPGES-1 leads to a significant tumorigenic gain in epithelial cells, and provide clues for controlling the vicious association. PMID- 22081068 TI - Cancer-associated alteration of pericentromeric heterochromatin may contribute to chromosome instability. AB - Many tumors exhibit elevated chromosome mis-segregation termed chromosome instability (CIN), which is likely to be a potent driver of tumor progression and drug resistance. Causes of CIN are poorly understood but probably include prior genome tetraploidization, centrosome amplification and mitotic checkpoint defects. This study identifies epigenetic alteration of the centromere as a potential contributor to the CIN phenotype. The centromere controls chromosome segregation and consists of higher-order repeat (HOR) alpha-satellite DNA packaged into two chromatin domains: the kinetochore, harboring the centromere specific H3 variant centromere protein A (CENP-A), and the pericentromeric heterochromatin, considered important for cohesion. Perturbation of centromeric chromatin in model systems causes CIN. As cancer cells exhibit widespread chromatin changes, we hypothesized that pericentromeric chromatin structure could also be affected, contributing to CIN. Cytological and chromatin immunoprecipitation and PCR (ChIP-PCR)-based analyses of HT1080 cancer cells showed that only one of the two HORs on chromosomes 5 and 7 incorporate CENP-A, an organization conserved in all normal and cancer-derived cells examined. Contrastingly, the heterochromatin marker H3K9me3 (trimethylation of H3 lysine 9) mapped to all four HORs and ChIP-PCR showed an altered pattern of H3K9me3 in cancer cell lines and breast tumors, consistent with a reduction on the kinetochore-forming HORs. The JMJD2B demethylase is overexpressed in breast tumors with a CIN phenotype, and overexpression of exogenous JMJD2B in cultured breast epithelial cells caused loss of centromere-associated H3K9me3 and increased CIN. These findings suggest that impaired maintenance of pericentromeric heterochromatin may contribute to CIN in cancer and be a novel therapeutic target. PMID- 22081069 TI - Atypical mechanism of NF-kappaB activation by TRE17/ubiquitin-specific protease 6 (USP6) oncogene and its requirement in tumorigenesis. AB - The NF-kappaB transcription factor has a central role in diverse processes, including inflammation, proliferation and cell survival, and its activity is dysregulated in diseases such as autoimmunity and cancer. We recently identified the TRE17/ubiquitin-specific protease 6 (USP6) oncogene as the first de ubiquitinating enzyme to activate NF-kappaB. TRE17/USP6 is translocated and overexpressed in aneurysmal bone cyst (ABC), a pediatric tumor characterized by extensive bone degradation and inflammatory recruitment. In the current study, we explore the mechanism by which TRE17 induces activation of NF-kappaB, and find that it activates the classical NF-kappaB pathway through an atypical mechanism that does not involve IkappaB degradation. TRE17 co-precipitates with IkappaB kinase (IKK), and IKK activity is augmented in stable cell lines overexpressing TRE17, in a USP-dependent manner. Optimal activation of NF-kappaB by TRE17 requires both catalytic subunits of IKK, distinguishing its mechanism from the classical and non-canonical pathways, which require either IKKbeta or IKKalpha, respectively. TRE17 stimulates phosphorylation of p65 at serine 536, a modification that has been associated with enhanced transcriptional activity and nuclear retention. Induction of S536 phosphorylation by TRE17 requires both IKKalpha and IKKbeta, as well as the IKKgamma/NEMO regulatory subunit of IKK. We further demonstrate that TRE17(long) is highly tumorigenic when overexpressed in NIH3T3 fibroblasts, and that inhibition of NF-kappaB significantly attenuates tumor formation. In summary, these studies uncover an unexpected signaling mechanism for activation of classical NF-kappaB by TRE17. They further reveal a critical role for NF-kappaB in TRE17-mediated tumorigenesis, and suggest that NF kappaB inhibitors may function as effective therapeutic agents in the treatment of ABC. PMID- 22081070 TI - The nuclear receptor TR3 regulates mTORC1 signaling in lung cancer cells expressing wild-type p53. AB - The orphan nuclear receptor TR3 (NR41A and Nur77) is overexpressed in most lung cancer patients and is a negative prognostic factor for patient survival. The function of TR3 was investigated in non-small-cell lung cancer A549 and H460 cells, and knockdown of TR3 by RNA interference (siTR3) inhibited cancer cell growth and induced apoptosis. The prosurvival activity of TR3 was due, in part, to formation of a p300/TR3/ specificity protein 1 complex bound to GC-rich promoter regions of survivin and other Sp-regulated genes (mechanism 1). However, in p53 wild-type A549 and H460 cells, siTR3 inhibited the mTORC1 pathway, and this was due to activation of p53 and induction of the p53-responsive gene sestrin 2, which subsequently activated the mTORC1 inhibitor AMP-activated protein kinase alpha (AMPKalpha) (mechanism 2). This demonstrates that the pro oncogenic activity of TR3 in lung cancer cells was due to inhibition of p53 and activation of mTORC1. 1,1-Bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C pPhOH) is a recently discovered inhibitor of TR3, which mimics the effects of siTR3. DIM-C-pPhOH inhibited growth and induced apoptosis in lung cancer cells and lung tumors in murine orthotopic and metastatic models, and this was accompanied by decreased expression of survivin and inhibition of mTORC1 signaling, demonstrating that inactivators of TR3 represent a novel class of mTORC1 inhibitors. PMID- 22081071 TI - Cathepsin D is partly endocytosed by the LRP1 receptor and inhibits LRP1 regulated intramembrane proteolysis. AB - The aspartic protease cathepsin-D (cath-D) is a marker of poor prognosis in breast cancer that is overexpressed and hypersecreted by human breast cancer cells. Secreted pro-cath-D binds to the extracellular domain of the beta-chain of the LDL receptor-related protein-1 (LRP1) in fibroblasts. The LRP1 receptor has an 85-kDa transmembrane beta-chain and a noncovalently attached 515-kDa extracellular alpha-chain. LRP1 acts by (1) internalizing many ligands via its alpha-chain, (2) activating signaling pathways by phosphorylating the LRP1beta chain tyrosine and (3) modulating gene transcription by regulated intramembrane proteolysis (RIP) of its beta-chain. LRP1 RIP involves two cleavages: the first liberates the LRP1 ectodomain to give a membrane-associated form, LRP1beta-CTF, and the second generates the LRP1beta-intracellular domain, LRP1beta-ICD, that modulates gene transcription. Here, we investigated the endocytosis of pro-cath-D by LRP1 and the effect of pro-cath-D/LRP1beta interaction on LRP1beta tyrosine phosphorylation and/or LRP1beta RIP. Our results indicate that pro-cath-D was partially endocytosed by LRP1 in fibroblasts. However, pro-cath-D and ectopic cath-D did not stimulate phosphorylation of the LRP1beta-chain tyrosine. Interestingly, ectopic cath-D and its catalytically inactive (D231N)cath-D, and pro-(D231N)cath-D all significantly inhibited LRP1 RIP by preventing LRP1beta-CTF production. Thus, cath-D inhibits LRP1 RIP independently of its catalytic activity by blocking the first cleavage. As cath-D triggers fibroblast outgrowth by LRP1, we propose that cath-D modulates the growth of fibroblasts by inhibiting LRP1 RIP in the breast tumor microenvironment. PMID- 22081072 TI - Mice deficient in MIM expression are predisposed to lymphomagenesis. AB - Missing in metastasis (MIM) is a member of newly emerged inverse Bin-Amphiphysin Rvs (BAR) domain protein family and a putative metastasis suppressor. Although reduced MIM expression has been associated with bladder, breast and gastric cancers, evidence for the role of MIM in tumor progression remains scarce and controversial. Herein we characterized a MIM knockout mouse strain and observed that MIM-deficient mice often developed enlarged spleens. Autopsy and histological analysis revealed that nearly 78% of MIM(-/-) mice developed tumors with features similar to diffuse large B lymphoma during a period from 1 to 2 years. MIM(-/-) mice also exhibited abnormal distribution of B cells in lymphoid organs with decrease in the spleen but increase in the bone marrow and the peripheral blood. Furthermore, the bone marrow of MIM(-/-) mice contained a higher percentage of pre-B2 cells but fewer immature B-cells than wild-type mice. In response to CXCL13, a B-cell chemokine released from splenic stromal cells, MIM-deficient B-cells did not undergo chemotaxis or morphological changes in response to the chemokine and also did not internalize CXCR5, the receptor of CXCL13. Microarray analyses demonstrated that MIM is the only member of the I-BAR domain family that was highly expressed in human B cells. However, low or absent MIM expression was common in either primary B-cell malignancies or established B cell acute lymphocytic leukemia or lymphomas. Thus, our data demonstrate for the first time an important role for MIM in B-cell development and suggest that predisposition of MIM-null mice to lymphomagenesis may involve aberrant interactions between B lineage cells and the lymphoid microenvironment. PMID- 22081073 TI - Recruitment of RPL11 at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and in an Mdm2-dependent manner. AB - Ribosomal proteins (RPs) activate the p53 tumour-suppressor protein upon disruption of the nucleolus. However, the exact mechanisms for p53 transcriptional activation through RPs are not well understood. We show that the RPL11 is rapidly but transiently recruited at promoter sites of p53-regulated genes upon nucleolar stress induced by actinomycin D (ActD). Characterisation of molecular events at p53 promoter sites shows that L11 is required for the recruitment of p53 transcriptional co-activators p300/CBP and p53 K382 acetylation. We found that direct binding to Mdm2 E3 ligase and NEDDylation of L11 are critical regulators for L11 promoter recruitment. Our data suggest that binding of L11 to Mdm2 at the promoter results in relief from Mdm2-mediated transcriptional repression of p53. Analysis of chromatin and RNA polymerase II markers suggests that L11 is involved in the initiation step of transcriptional activation. Furthermore, analysis of 36 ActD-induced genes shows that L11 and NEDD8 are global regulators of the p53 activation response. The studies provide insights on how nucleolar stress through L11 and NEDD8 can activate the transcriptional activity of p53. PMID- 22081075 TI - Bim must be able to engage all pro-survival Bcl-2 family members for efficient tumor suppression. AB - Overexpression of the transcriptional regulator Myc is thought to be the cause or a contributing factor in the development of a large number of human lymphomas and certain other cancers. Apoptotic cell death constitutes a tumor suppressive mechanism, particularly in the context of Myc overexpression. Accordingly, lymphoma development in EMU-Myc transgenic mice, which mimic the Myc/IgH chromosomal translocation that causes Burkitt lymphoma, is accelerated by concomitant overexpression of anti-apoptotic Bcl-2 family members or loss of pro apoptotic BH3-only proteins, such as Bim. Bim binds with high affinity to all pro survival Bcl-2-like proteins and can also interact with Bax/Bak, but it remains unclear which of these interactions are critical for its tumor suppressive function. We have previously generated knock-in mutant mice in which the BH3 region of Bim has been exchanged with that for Bad, Noxa or Puma so that it can only bind to select pro-survival Bcl-2-like proteins: Bim(Bad) binding to Bcl-2, Bcl-x(L) and Bcl-w, but not Mcl-1 or A1; Bim(Noxa) binding only to Mcl-1 and A1 and as a control, Bim(Puma), which can still bind all pro-survival Bcl-2-like proteins. We have now inter-crossed these Bim mutant mice with EMU-Myc transgenic mice, and found that both the Bim(Bad) and the Bim(Noxa) mutations but not the Bim(Puma) mutation greatly accelerate Myc-induced lymphoma development and increase leukemic burden. These results demonstrate that for optimal tumor suppressive activity, Bim must be able to interact with all and not just select pro-survival Bcl-2 family members. PMID- 22081074 TI - PTTG induces EMT through integrin alphaVbeta3-focal adhesion kinase signaling in lung cancer cells. AB - Pituitary tumor transforming gene (PTTG) is a well-studied oncogene for its role in tumorigenesis and serves as a marker of malignancy in several cancer types including lung. In the present study, we defined the role of PTTG in actin cytoskeleton remodeling, cell migration and induction of epithelial mesenchymal transition (EMT) through the regulation of integrin alpha(V)beta(3)-FAK (focal adhesion kinase) signaling pathway. Overexpression of PTTG through an adenovirus vector resulted in a significant increase in the expression of integrins alpha(V) and beta(3), a process that was reversed with the downregulation of PTTG expression through the use of an adenovirus expressing PTTG-specific small interfering RNA (siRNA). Western blot analysis of cells infected with adenovirus PTTG cDNA resulted in increased FAK and enhanced expression of adhesion complex molecules paxillin, metavincullin, and talin. Furthermore, downstream signaling genes Rac1, RhoA, Cdc42 and DOCK180 showed upregulation upon PTTG overexpression. This process was dependent on integrin alpha(V), as blockage by antagonist echistatin (RGD peptide) or alpha(V)-specific siRNA resulted in a decrease in FAK and subsequent adhesion molecules. Actin cytoskeleton disruption was detected as a result of integrin-FAK signaling by PTTG as well as enhanced cell motility. Taken together, our results suggest for the first time an important role of PTTG in regulation of integrins alpha(V) and beta(3) and adhesion-complex proteins leading to induction of EMT. PMID- 22081076 TI - LIN28: a regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer. AB - A tumor-suppressor gene, let-7 microRNA (miRNA) family, is often inactivated in various human malignancies. LIN28 is a RNA-binding protein that has been well characterized for regulation of let-7 maturation in undifferentiated embryonic stem cells at post-transcriptional level. Oncogenic regulation of let-7 miRNAs has been demonstrated in several human malignancies but their correlation with LIN28 has not been studied in breast cancer. We therefore explored a possible mechanism of tumorigenesis in breast carcinoma tissue via an alternation of let-7 miRNA precursor processing by LIN28 in this study. A total of 26 breast cancer surgical pathology specimens were evaluated for LIN28 and LIN28B expression using immunohistochemistry. We then isolated carcinoma cells in 21 cases using laser capture microdissection, and the miRNAs from these samples were profiled using PCR array analysis. LIN28 status was positively correlated with ERalpha, PR, and Ki-67 status and inversely correlated with HER2 status. These results suggest the possible involvement of LIN28 in regulation of sex steroid dependent cell proliferation of breast carcinoma cells. We further demonstrated that expression of let-7a, let-7c, let-7d (P=0.026) and let-7f (P=0.016) were inversely correlated with those of LIN28. These results also suggest that LIN28 promotes tumorigenic activity by suppressing let-7 miRNA maturation in breast carcinoma cells. PMID- 22081077 TI - Preimplantation genetic diagnosis for couples with a Robertsonian translocation: practical information for genetic counseling. AB - PURPOSE: To evaluate the proportions of abnormal and normal embryos detected by preimplantation genetic diagnosis (PGD) of infertile couples of whom one was a Robertsonian translocation (RT) carrier, and to provide practical information, including details of reproductive outcomes, to aid in genetic counseling of such couples. METHODS: We retrospectively analyzed all PGD cycles conducted to deal with RT at our center between January 2000 and December 2009. Subject demographic and clinical data were compared with the results of PGD. RESULTS: Employing PGD, we conducted a total of 66 cycles on 34 couples of whom one was an RT carrier, including 24 female and 10 male carriers. Of the 514 blastomeres tested, 161 (31.3%) were normal or balanced. Of the 57 cycles that included embryo transfer, 17 (29.8%) attained positivity for human chorionic gonadotropin (hCG). A total of 17 embryos were implanted and 16 babies, including two sets of twins, were born. The takehome baby rate was 41.2% per couple and the loss rate 6.6%. Receiver operating characteristic curve analysis showed that the proportion of alternate embryos associated with a sensitivity of 70.6% for prediction of clinical pregnancy following PGD was 0.31. Sex of the carrier and type of translocation were not significantly associated with pregnancy outcomes. CONCLUSION: Couples with RT may benefit from PGD; pregnancy success rate is improved and embryo loss reduced. We found that about 30% of embryos were of normal or balanced chromosomal constitution and that the percentage of normal or balanced embryos was predictive of PGD outcome. PMID- 22081080 TI - Magnetoelastic metamaterials. AB - The study of advanced artificial electromagnetic materials, known as metamaterials, provides a link from material science to theoretical and applied electrodynamics, as well as to electrical engineering. Being initially intended mainly to achieve negative refraction, the concept of metamaterials quickly covered a much broader range of applications, from microwaves to optics and even acoustics. In particular, nonlinear metamaterials established a new research direction giving rise to fruitful ideas for tunable and active artificial materials. Here we introduce the concept of magnetoelastic metamaterials, where a new type of nonlinear response emerges from mutual interaction. This is achieved by providing a mechanical degree of freedom so that the electromagnetic interaction in the metamaterial lattice is coupled to elastic interaction. This enables the electromagnetically induced forces to change the metamaterial structure, dynamically tuning its effective properties. This concept leads to a new generation of metamaterials, and can be compared to such fundamental concepts of modern physics as optomechanics of photonic structures or magnetoelasticity in magnetic materials. PMID- 22081081 TI - Induction of coherent magnetization switching in a few atomic layers of FeCo using voltage pulses. AB - The magnetization direction of a metallic magnet has generally been controlled by a magnetic field or by spin-current injection into nanosized magnetic cells. Both these methods use an electric current to control the magnetization direction; therefore, they are energy consuming. Magnetization control using an electric field is considered desirable because of its expected ultra-low power consumption and coherent behaviour. Previous experimental approaches towards achieving voltage control of magnetization switching have used single ferromagnetic layers with and without piezoelectric materials, ferromagnetic semiconductors, multiferroic materials, and their hybrid systems. However, the coherent control of magnetization using voltage signals has not thus far been realized. Also, bistable magnetization switching (which is essential in information storage) possesses intrinsic difficulties because an electric field does not break time reversal symmetry. Here, we demonstrate a coherent precessional magnetization switching using electric field pulses in nanoscale magnetic cells with a few atomic FeCo (001) epitaxial layers adjacent to a MgO barrier. Furthermore, we demonstrate the realization of bistable toggle switching using the coherent precessions. The estimated power consumption for single switching in the ideal equivalent switching circuit can be of the order of 10(4)k(B)T, suggesting a reduction factor of 1/500 when compared with that of the spin-current-injection switching process. PMID- 22081082 TI - Fano-resonant asymmetric metamaterials for ultrasensitive spectroscopy and identification of molecular monolayers. AB - Engineered optical metamaterials present a unique platform for biosensing applications owing to their ability to confine light to nanoscale regions and to their spectral selectivity. Infrared plasmonic metamaterials are especially attractive because their resonant response can be accurately tuned to that of the vibrational modes of the target biomolecules. Here we introduce an infrared plasmonic surface based on a Fano-resonant asymmetric metamaterial exhibiting sharp resonances caused by the interference between subradiant and superradiant plasmonic resonances. Owing to the metamaterial's asymmetry, the frequency of the subradiant resonance can be precisely determined and matched to the molecule's vibrational fingerprints. A multipixel array of Fano-resonant asymmetric metamaterials is used as a platform for multispectral biosensing of nanometre scale monolayers of recognition proteins and their surface orientation, as well as for detecting chemical binding of target antibodies to recognition proteins. PMID- 22081083 TI - Conductive dense hydrogen. AB - Molecular hydrogen is expected to exhibit metallic properties under megabar pressures. This metal is predicted to be superconducting with a very high critical temperature, T(c), of 200-400 K, and it may acquire a new quantum state as a metallic superfluid and a superconducting superfluid. It may potentially be recovered metastably at ambient pressures. However, experiments carried out at low temperatures, T<100 K, showed that at record pressures of 300 GPa, hydrogen remains in the molecular insulating state. Here we report on the transformation of normal molecular hydrogen at room temperature (295 K) to a conductive and metallic state. At 200 GPa the Raman frequency of the molecular vibron strongly decreased and the spectral width increased, evidencing a strong interaction between molecules. Deuterium behaved similarly. Above 220 GPa, hydrogen became opaque and electrically conductive. At 260-270 GPa, hydrogen transformed into a metal as the conductance of hydrogen sharply increased and changed little on further pressurizing up to 300 GPa or cooling to at least 30 K; and the sample reflected light well. The metallic phase transformed back at 295 K into molecular hydrogen at 200 GPa. This significant hysteresis indicates that the transformation of molecular hydrogen into a metal is accompanied by a first-order structural transition presumably into a monatomic liquid state. Our findings open an avenue for detailed and comprehensive studies of metallic hydrogen. PMID- 22081084 TI - Electric-field-assisted switching in magnetic tunnel junctions. AB - The advent of spin transfer torque effect accommodates site-specific switching of magnetic nanostructures by current alone without magnetic field. However, the critical current density required for usual spin torque switching remains stubbornly high around 10(6)-10(7) A cm(-2). It would be fundamentally transformative if an electric field through a voltage could assist or accomplish the switching of ferromagnets. Here we report electric-field-assisted reversible switching in CoFeB/MgO/CoFeB magnetic tunnel junctions with interfacial perpendicular magnetic anisotropy, where the coercivity, the magnetic configuration and the tunnelling magnetoresistance can be manipulated by voltage pulses associated with much smaller current densities. These results represent a crucial step towards ultralow energy switching in magnetic tunnel junctions, and open a new avenue for exploring other voltage-controlled spintronic devices. PMID- 22081085 TI - All-silica nanofluidic devices for DNA-analysis fabricated by imprint of sol-gel silica with silicon stamp. AB - We present a simple and cheap method for fabrication of silica nanofluidic devices for single-molecule studies. By imprinting sol-gel materials with a multi level stamp comprising micro- and nanofeatures, channels of different depth are produced in a single process step. Calcination of the imprinted hybrid sol-gel material produces purely inorganic silica, which has very low autofluorescence and can be fusion bonded to a glass lid. Compared to top-down processing of fused silica or silicon substrates, imprint of sol-gel silica enables fabrication of high-quality nanofluidic devices without expensive high-vacuum lithography and etching techniques. The applicability of the fabricated device for single molecule studies is demonstrated by measuring the extension of DNA molecules of different lengths confined in the nanochannels. PMID- 22081086 TI - Injection port silylation of gamma-hydroxybutyrate and trans-hydroxycrotonic acid: conditions optimisation and characterisation of the di-tert butyldimethylsilyl derivatives by GC-MS. AB - Silylation is usually carried out on gamma-hydroxybutyrate (GHB) for its analysis by Gas Chromatography/Mass Spectrometry (GCMS) and requires potentially long incubation times before injection during which the derivatisation reagent and derivatives (such as trimethyl-silyl compounds) can hydrolyse. Moreover, alternative internal standards (IS) are often useful depending on sample matrices, extraction/purification procedures, commercial availability and price. This study evaluated the possibility of silylating GHB with an injection port derivatisation procedure using N-methyl-N-[tert-butyldimethyl silyl]trifluoroacetimide (MTBSTFA) with 1% tert-butyldimethylchlorosilane (TBCS) as the derivatisation reagent, producing di-tert-butyldimethyl-silyl derivatives as a novel means of analyzing GHB. In parallel, trans-hydroxycrotonic acid (t HCA) was investigated as a potential IS for GHB quantification. Analyses were carried out with a temperature programmable injector and the GHB(t-BDMS)(2) and t HCA(t-BDMS)(2) derivatives were successfully produced, characterised and derivatisation conditions optimised. t-HCA behaved very similarly to GHB through the derivatisation processes and was used as the IS for the determination of urinary endogenous GHB concentrations in human subjects where the method showed a limit of detection of 0.049 MUg mL(-1), a limit of quantification of 0.162 MUg mL(-1), and a limit of confirmation of 1.33 MUg mL(-1), suitable for toxicological GHB concentration determination. PMID- 22081087 TI - Wavelike deformation traveling on a carbon nanotube. AB - The propagation of wavelike ripples on a carbon nanotube (CNT) induced by the radial impact of a C(60) molecule is investigated by molecular dynamics simulations. The ripples start at the impact point and spreads through the tube, accompanied by energy transfer. The ripples would effectively reduce the local energy concentration around the impact point. The propagation of ripples is clearly affected by the diameter but is independent of the chirality of the CNT. Noticeable diffraction occurs when the deformation ripples encounter obstacles or narrow slits, which indicates that the propagation of ripples can be used to detect defects in the CNT. This work provides new and exciting possibilities for CNTs to serve as energy buffers, sensors and new nanoelectromechanical devices. PMID- 22081088 TI - Stepping down asthma treatment: how and when. AB - PURPOSE OF REVIEW: Guidelines suggest that asthma medication should be reduced once asthma control is sustained. Moderate-dose inhaled corticosteroids (ICS) can typically be reduced, but questions remain about the lowest effective ICS dose and the role of non-ICS controllers in treatment reduction. Long-acting beta agonist (LABA) safety concerns have created controversy about how to step down patients on ICS/LABA therapy. This review will focus on the current status of these issues. RECENT FINDINGS: Intermittent ICS treatment, often in fixed combination with short-acting beta agonist, is an emerging strategy for control of mild asthma. Addition of leukotriene modifiers, LABAs, and omalizumab to ICS can allow for reduced ICS dosing. Doses of ICS that control symptoms may be inadequate to control exacerbations. Reducing ICS dose before discontinuing LABAs may be the more effective approach for patients on combination therapy. SUMMARY: Use of non-ICS controllers allows for ICS dose reduction with superior outcomes. Tapering of ICS prior to LABA discontinuation may be the favored approach for patients on ICS/LABA therapy, but an understanding of long-term outcomes and further safety data are required. The lowest ICS dose that adequately controls both asthma impairment and risk remains to be determined. PMID- 22081089 TI - Measures of asthma control. AB - PURPOSE OF REVIEW: Over the past decade, the concept of asthma control as distinct from asthma severity has been clearly defined. Well controlled asthma is the goal of therapy in all asthma patients. This review is a comprehensive description of the tools currently available for a methodical assessment of different aspects of asthma control in clinical practice and research. RECENT FINDINGS: Several questionnaires for assessing asthma control have been extensively validated in adults. In children, validation data are less extensive. Considerable overlap exists between asthma control measures and measures of asthma-specific quality of life. Asthma-specific quality-of-life questionnaires have been used as primary outcome measures in major clinical trials evaluating asthma therapy. Biomarkers that reflect eosinophilic inflammation of the airways are used as intermediate outcome measures to reflect the biological basis of asthma control. There is some controversy, however, over which biomarkers are best incorporated into therapeutic algorithms that attempt to achieve maximal asthma control while minimizing treatment intensity. SUMMARY: In designing clinical studies to evaluate different asthma therapies, researchers will find this review to be a useful resource in terms of choosing the appropriate tool for assessing asthma control. This is also a valuable resource for a methodical assessment of response to asthma therapy in routine clinical care. PMID- 22081090 TI - The indoor air and asthma: the role of cat allergens. AB - PURPOSE OF REVIEW: The objective is to discuss recent progress in our understanding of the role of the indoor environment in asthma, focusing on the special role of cat allergens. RECENT FINDINGS: Sensitization to Fel d 1 is the dominant event in inhalant responses to cat; however, there are also IgE responses to the lipocalin (Fel d 4), to cat albumin (Fel d 2), and to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) on cat IgA (Fel d 5w) and other molecules. The dose response and routes of sensitization for these allergens are now thought to be diverse. It is important to remember that exposure outside a house with a cat is sufficient to cause sensitization. Furthermore, the only solid evidence about a role in asthma relates to Fel d 1. Recently, it has been shown that tolerance associated with early exposure to cats can persist to age 18 and that IgE to alpha-gal (on cat IgA) is not related to asthma. In addition, a recent study of anti-IgE reinforces the evidence that IgE antibodies to indoor allergens make a major contribution to asthma severity. SUMMARY: Exposure to Fel d 1 in a home with a cat is far higher than the levels necessary to induce an allergic (IgE antibody) response. In keeping with that, children may develop tolerance, which can be long-lived. In addition, there is increasing evidence that IgE antibodies to an inhalant allergen, such as Fel d 1, dust mite, or cockroach, are causally related to lung inflammation and asthma. PMID- 22081091 TI - Predicting asthma exacerbations in children. AB - PURPOSE OF REVIEW: This review critically assesses recently published literature on predicting asthma exacerbations in children, while also providing general recommendations for future research in this field. RECENT FINDINGS: Current evidence suggests that every effort should be made to provide optimal treatment to achieve adequate asthma control, as this will significantly reduce the risk of severe disease exacerbations. Children who have had at least one asthma exacerbation in the previous year are at highest risk for subsequent exacerbations, regardless of disease severity and/or control. Although several tools and biomarkers to predict asthma exacerbations have been recently developed, these approaches need further validation and/or have only had partial success in identifying children at risk. SUMMARY: Although considerable progress has been made, much remains to be done. Future studies should clearly differentiate severe asthma exacerbations due to inadequate asthma control from those occurring in children whose asthma is well controlled, utilize standardized definitions of asthma exacerbations, and use a systematic approach to identify the best predictors after accounting for the multiple dimensions of the problem. Our ability to correctly predict the development of severe asthma exacerbations in an individual child should improve in parallel with increased knowledge and/or understanding of the complex interactions among genetic, environmental (e.g. viral infections) and lifestyle (e.g. adherence to treatment) factors underlying these events. PMID- 22081092 TI - Fibroblast polarization is a matrix-rigidity-dependent process controlled by focal adhesion mechanosensing. AB - Cell elongation and polarization are basic morphogenetic responses to extracellular matrix adhesion. We demonstrate here that human cultured fibroblasts readily polarize when plated on rigid, but not on compliant, substrates. On rigid surfaces, large and uniformly oriented focal adhesions are formed, whereas cells plated on compliant substrates form numerous small and radially oriented adhesions. Live-cell monitoring showed that focal adhesion alignment precedes the overall elongation of the cell, indicating that focal adhesion orientation may direct cell polarization. siRNA-mediated knockdown of 85 human protein tyrosine kinases (PTKs) induced distinct alterations in the cell polarization response, as well as diverse changes in cell traction force generation and focal adhesion formation. Remarkably, changes in rigidity dependent traction force development, or focal adhesion mechanosensing, were consistently accompanied by abnormalities in the cell polarization response. We propose that the different stages of cell polarization are regulated by multiple, PTK-dependent molecular checkpoints that jointly control cell contractility and focal-adhesion-mediated mechanosensing. PMID- 22081093 TI - A new cap for kinetochore fibre minus ends. AB - In mitotic spindles, each sister chromatid is directly attached to a spindle pole through microtubule bundles known as kinetochore fibres. Microspherule protein 1 (MCRS1) is now shown to support spindle assembly by localizing to the minus ends of kinetochore fibres and protecting them from depolymerization. PMID- 22081094 TI - K-fibre minus ends are stabilized by a RanGTP-dependent mechanism essential for functional spindle assembly. AB - Chromosome segregation requires the formation of K-fibres, microtubule bundles that attach sister kinetochores to spindle poles. Most K-fibre microtubules originate around the chromosomes through a non-centrosomal RanGTP-dependent pathway and become oriented with the plus ends attached to the kinetochore and the minus ends focused at the spindle poles. The capture and stabilization of microtubule plus ends at the kinetochore has been extensively studied but very little is known on how their minus-end dynamics are controlled. Here we show that MCRS1 is a RanGTP-regulated factor essential for non-centrosomal microtubule assembly. MCRS1 localizes to the minus ends of chromosomal microtubules and K fibres, where it protects them from depolymerization. Our data reveal the existence of a mechanism that stabilizes the minus ends of chromosomal microtubules and K-fibres, and is essential for the assembly of a functional bipolar spindle. PMID- 22081095 TI - Transarterial endovascular treatment in the management of life-threatening intra- and postoperative haemorrhages after otorhinolaryngological surgery. AB - Management of life-threatening postsurgical bleeding is complex. If conservative or surgical therapy is demanding, an endovascular treatment can be considered. The goal of this study was to evaluate the outcome of endovascular approaches in the diagnosis and therapy of otherwise intractable postoperative haemorrhages with a study design of outcomes research. Charts of all patients with postsurgical bleedings receiving endovascular treatment were reviewed for clinical outcome, complications, and demographic data. 15 patients were identified. They had rhinosurgery (12/15), tonsillectomy (2/15) or transoral tumour debulking (1/15) prior to the endovascular procedure. In more than 70%, the source of bleeding was directly located angiographically and subsequently superselectively embolized. The remaining patients suffered from post rhinosurgical epistaxis and underwent a bilateral embolization of the sphenopalatine artery. All bleedings were successfully controlled and no procedure-related complication was noted. In conclusion, endovascular treatment of life-threatening postsurgical haemorrhages should be considered if the source of bleeding is unknown or if surgery is difficult and may result in devastating postoperative complications. PMID- 22081096 TI - Tropomyosin sensitization in house dust mite allergic patients. AB - The growing popularity and frequency of consumption of seafood is accompanied by an increasing number of adverse reactions reported in literature. Allergic reactions to seafood can generate a variety of symptoms ranging from a mild oral allergy syndrome to keen anaphylactic reactions. Tropomyosin, the major shellfish allergen is regarded to be responsible for clinical cross-reactivity to inhaled house dust mites. The aim of the study was to investigate the prevalence of sensitization to tropomyosin in house dust mite allergic patients in southern Bavaria and to compare the results with allergic symptoms. Sera of house dust mite allergic patients (positive skin prick test, allergen-specific IgE and intranasal provocation) were screened for IgE antibodies to tropomyosin (Der p 10). Patients were contacted by phone to evaluate allergic symptoms when consuming seafood. IgE antibodies to house dust mite tropomyosin (Der p 10) could be found in 4 out of 93 sera (4.3%). Two of these four patients (50%) showed itching and swelling of oral mucosa accompanied by bronchial obstruction after consumption of shrimp. Two patients had no problems when eating seafood. None of the seronegative patients complained about any health problems during or after consumption of seafood. In conclusion, cross-reactivity to tropomyosin in house dust mite allergic patients in southern Bavaria, Germany is rarer than suspected. Beside the direct allergic reactions, a further part of reactions to seafood must therefore be ascribed to other mechanisms such as intoxication or intolerance to, e.g. additives in the food product. PMID- 22081097 TI - Ear melanoma: influence of perichondrium involvement in evaluating surgical strategy. AB - Adequate treatment of melanomas of the external ear offers unique surgical challenges because of the complex anatomical features of the auricle and the need for proper oncologic aggressiveness, as well as for valid aesthetic results. In this study, we evaluated nine different cases of melanoma of the auricle treated in our Institute between 1994 and 2008. Every enrolled patient underwent surgical excision, nonetheless reconstruction was performed with different surgical techniques. In accordance with histological reports, we could observe the absence of neoplastic cells in perichondral bone and in cartilagenous tissue, providing further assurance concerning the importance of preserving the outer ear in expectation of reconstruction. As a matter of fact, it has been proven that it is possible to reconstruct the auricle while guaranteeing oncologic safety in melanomas with a Breslow thickness >1 mm. Therefore, an excision preserving the cartilagenous tissue, thus allowing an efficient full-thickness cutaneous grafting may guarantee good functional and aesthetic results. In conclusion, the suggested therapeutic management may be considered in <1 mm melanomas without taking further unnecessary oncologic risks. PMID- 22081098 TI - Biomarkers predicting malignant progression of laryngeal epithelial precursor lesions: a systematic review. AB - Some laryngeal epithelial precursor lesions progress to invasive carcinoma and others do not. Routine light microscopic classification has limited value in predicting the evolution of these lesions. This article reviews the experience to date with the use of molecular markers for the prognostic evaluation of laryngeal epithelial precursor lesions. We conducted a thorough review of the published literature to identify those studies using biomarkers to predict malignant progression of laryngeal epithelial precursor lesions. Of the 336 studies identified in this systematic search, 15 met the inclusion criteria and form the basis of this review. Limited studies suggest that certain biomarkers are potentially reliable predictors of malignant progression including various regulators of cell adhesion and invasion (e.g. FAK, cortactin, osteopontin, and CD44v6) and proliferation-associated markers such as TGF-betaRII and Kv3.4. The predictive value of these markers, however, has yet to be confirmed in large scale prospective studies. Although the cell cycle-related proteins are the most frequently studied markers, none have been consistently reliable across multiple studies. The absence of standardization in methodologies, test interpretation, and other parameters may contribute to study inconsistencies. Various biomarkers have proved to have potential prognostic value and could be clinically relevant. The utility and prognostic power of these biomarkers should be confirmed in large, well-designed, standardized prospective studies. PMID- 22081099 TI - Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years. AB - The objective of this study was to describe a large Italian cohort of patients with late-onset glycogen storage disease type 2 (GSDII) at various stages of disease progression and to evaluate the clinical effectiveness of alglucosidase alpha enzyme replacement therapy (ERT). Previous studies showed in late-onset patients ERT efficacy against placebo and variable response in uncontrolled studies. Seventy-four juvenile or adult GSDII patients were treated with ERT in a multicenter open label, non-randomized study, from 12 months up to 54 months. Recombinant human alpha glucosidase (rh-GAA) was injected by intravenous route at 20 mg/kg every second week. Patients were divided into three groups according to ERT duration: Group A received treatment for 12-23 months (n = 16), Group B for 24-35 months (n = 14), and Group C for more than 36 months (n = 44). Clinical assessment included a 6-min walk test (6MWT), forced vital capacity (FVC), the Walton and Gardner-Medwin score, the number of hours of ventilation, body mass index, echocardiography and blood creatine kinase (CK). Included in our cohort were 33 males and 41 females (M:F = 0.8:1), with a mean age at first symptoms of 28.3 years (range 2-55 years) and a mean age of 43 years at study entry (range 7 72 years). Seven wheelchair bound patients, as well as 27 patients requiring ventilation support, were included. After treatment we could observe an increase in distance walked on the 6MWT in the large majority of patients (48/58; 83%), with an overall mean increase of 63 m (from 320 +/- 161 to 383 +/- 178 m). After treatment in the majority of patients FVC was improved or unchanged (45/69; 65%). In ventilated patients we observed an improvement in average number of hours off the ventilator (from 15.6 to 12.1 h). Six patients stopped mechanical ventilation and two others started it. The effect of therapy was not related to ERT duration. Nine of 64 patients (13%) that underwent to echocardiography showed a variable degree of cardiac hypertrophy (left ventriculum or septum), and a positive effect was observed after 36 months of ERT in one adult case. Discontinuation of treatment occurred in four patients: one drop-off case, one patient died for a sepsis after 34 months of treatment and two patients stopped ERT for worsening of general clinical condition. Mild adverse effects were observed in four cases (5%). This study represents the largest cohort of late-onset GSDII patients treated with ERT, and confirm a positive effect of treatment. These results, obtained in a large case series on therapy, indicate a favourable effect of ERT therapy, even in more advanced stage of the disease. PMID- 22081100 TI - Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients. AB - Patients in a minimally conscious state (MCS) show restricted signs of awareness but are unable to communicate. We assessed cerebral glucose metabolism in MCS patients and tested the hypothesis that this entity can be subcategorized into MCS- (i.e., patients only showing nonreflex behavior such as visual pursuit, localization of noxious stimulation and/or contingent behavior) and MCS+ (i.e., patients showing command following).Patterns of cerebral glucose metabolism were studied using [(18)F]-fluorodeoxyglucose-PET in 39 healthy volunteers (aged 46 +/ 18 years) and 27 MCS patients of whom 13 were MCS- (aged 49 +/- 19 years; 4 traumatic; 21 +/- 23 months post injury) and 14 MCS+ (aged 43 +/- 19 years; 5 traumatic; 19 +/- 26 months post injury). Results were thresholded for significance at false discovery rate corrected p < 0.05.We observed a metabolic impairment in a bilateral subcortical (thalamus and caudate) and cortical (fronto temporo-parietal) network in nontraumatic and traumatic MCS patients. Compared to MCS-, patients in MCS+ showed higher cerebral metabolism in left-sided cortical areas encompassing the language network, premotor, presupplementary motor, and sensorimotor cortices. A functional connectivity study showed that Broca's region was disconnected from the rest of the language network, mesiofrontal and cerebellar areas in MCS- as compared to MCS+ patients.The proposed subcategorization of MCS based on the presence or absence of command following showed a different functional neuroanatomy. MCS- is characterized by preserved right hemispheric cortical metabolism interpreted as evidence of residual sensory consciousness. MCS+ patients showed preserved metabolism and functional connectivity in language networks arguably reflecting some additional higher order or extended consciousness albeit devoid of clinical verbal or nonverbal expression. PMID- 22081101 TI - Neurolathyrism: two Ethiopian case reports and review of the literature. AB - Neurolathyrism is a toxic myelopathy caused by ingestion of the Lathyrus sativus grasspea. An irreversible acute to subacute spastic paraparesis or quadriparesis ensues. Despite public education, new cases of this preventable disease still occur. Two Ethiopian cases of neurolathyrism are reported to illustrate the disease, followed by a literature review. Two teenage male farmers from the same village developed irreversible spastic myelopathy following L. sativus ingestion. There was no sensory, sphincter or bulbar dysfunction. Likely causative factors identified were increased consumption of L. sativus prior to and following disease onset, heavy physical exertion and male gender, similar to those reported in the literature. Neurolathyrism is an entirely preventable neurotoxic myelopathy with permanent disability accrued. Treatment is symptomatic. Because of personal disability and subsequent socioeconomic effects, this disease warrants further public health measures to prevent occurrence. Education, avoidance of the grasspea and measures to reduce toxin burden are possible methods. PMID- 22081102 TI - Striatal hypermetabolism in limbic encephalitis. AB - Striatal hypermetabolism on 18FDG-PET scan is a neuroradiological finding that has been described in association with autoimmune disorders such as Sydenham chorea, lupus or antiphospholipid syndrome. Here, we report three patients with non-paraneoplastic limbic encephalitis characterized by 18FDG-PET hypermetabolism of both striata, in contrast with diffuse hypometabolism in the rest of the brain. All patients developed subacute dementia, and antibodies to voltage-gated potassium channels were found in all cases. Brain metabolism and neurological status improved within a few months of immunosuppressive therapy. The finding of striatal hypermetabolism on 18FDG-PET images could thus be highly indicative of limbic encephalitis associated with anti-neuropil antibodies. It could be of significant help in the diagnosis of this rare and treatable condition, and may also provide a useful marker of disease outcome. PMID- 22081103 TI - Focal pseudohypertrophy of the left hemi-tongue. PMID- 22081104 TI - Intratumoural lymph vessel density is related to presence of lymph node metastases and separates encapsulated from infiltrative papillary thyroid carcinoma. AB - Papillary thyroid carcinoma (PTC) gives frequently rise to nodal metastases via lymphatic vessels while follicular thyroid carcinoma (FTC) metastasises mainly via blood vessels to lung and bones. The follicular variant of PTC (FVPTC) encompasses the infiltrative subtype (I-FVPTC), which shares most of the features of classic PTC (CPTC), and the encapsulated subtype (E-FVPTC), which appears to be related to minimally invasive FTC. In an attempt to contribute to the understanding of the aforementioned differences, we evaluated intratumoural and peritumoural lymph vessels density (LVD), using the immunomarker D2-40 in a series of E-FVPTC, I-FVPTC, and CPTC with known BRAF and RAS status. None of the E-FVPTC cases presented extra-thyroid extension, lymph vessel invasion or nodal metastases, at variance with I-FVPTC and CPTC cases. The BRAF V600E mutation was detected in 8.3% of E-FVPTC, 25.0% of I-FVPTC and in 40.7% of CPTC, while N-RAS Q61R mutation was detected only in 10.3% of FVPTC cases. Only one case of E-FVPTC (8.3%) had intratumoural D2-40-stained vessels in contrast to their presence in 76.5% of the cases of I-FVPTC. Intratumoural LVD determined by D2-40 expression correlated with the occurrence of extra-thyroid extension, lymph vessel invasion and lymph node metastases in PTC cases. At variance with intratumoural LVD, peritumoural LVD was not associated with any clinic-pathological or molecular feature, being similar in E-FVPTC, I-FVPTC and CPTC. Our study highlights the role of intratumoural lymph vessels in PTC nodal metastisation and reinforces the importance of distinguishing E-FVPTC from I-FVPTC regarding invasiveness, metastatic pattern and molecular profile. PMID- 22081105 TI - T cell/histiocyte-rich large B-cell lymphoma: an update on its biology and classification. AB - T cell/histiocyte-rich large B-cell lymphoma (THRLBCL), originally considered an uncommon variant of Diffuse Large B-Cell Lymphoma (DLBCL), is recognized by the World Health Organisation as a separate clinicopathological entity since 2008. It predominantly affects middle aged men often presenting with advanced stage disease frequently involving spleen, liver and bone marrow at time of diagnosis. According to the WHO, this lymphoma is morphologically characterized by less than 10% of large neoplastic B cells in a background of abundant T cells and frequently histiocytes. Differentiating THRLBCL from other lymphoproliferative disorders such as Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) and Lymphocyte-Rich classical Hodgkin lymphoma (LRcHL) is important from a clinical point of view and can be achieved in most cases, given adequate biopsy specimens, by careful morphological and immunohistochemical evaluation of both the neoplastic cells as well as the nonneoplastic stromal component. According to this WHO definition, THRLBCL is still considered a clinically heterogeneous entity, though it is noted that especially the cases containing numerous histiocytes behave aggressively and show resistance to current therapies for DLBCL. Gene expression profiling studies of THRLBCL provided evidence for a prominent role for this histiocytic component that is important for a tolerogenic host immune response in which they may assist neoplastic cells in escaping the T cell-mediated immune surveillance. Therefore, reserving the diagnosis of THRLBCL to cases containing a large proportion of histiocytes might be relevant, as modulating their activity could provide new therapeutic options. PMID- 22081106 TI - Cyclooxygenase-2 expression in esophageal epithelium before and after photodynamic therapy for Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma. AB - Cyclooxygenase-2 expression is upregulated in Barrett's esophagus and esophageal adenocarcinoma. Photodynamic therapy using porfimer sodium can result in ablation of dysplasia and intramucosal carcinoma, eradication of Barrett's esophagus, and restitution of squamous epithelium. The aim of this study was to determine the effect of photodynamic therapy on cyclooxygenase-2 expression in esophageal epithelium. Paired pre- and post-photodynamic therapy biopsy samples from the same anatomical levels of 20 individuals who had undergone photodynamic therapy for Barrett's esophagus with high-grade dysplasia and/or intramucosal carcinoma were immunostained using a cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was graded in squamous epithelium, Barrett's esophagus, and neoplasia (if present) as follows: grade 0 (no staining), grade 1 (staining in 1-10% of cells), grade 2 (staining in 11-90% of cells), and grade 3 (staining in >90% of cells). Pre-photodynamic therapy median cyclooxygenase-2 expression was grade 2 (range 1-3) in neoplastic foci and grade 1 (range 1-3) in nondysplastic Barrett's esophagus (P=0.0009 for pairwise comparison). With the exception of a few cells staining in the basal epithelial layers, median cyclooxygenase-2 expression was graded as 0 (similar to controls) in both pre-photodynamic therapy squamous epithelium and post-photodynamic therapy neosquamous epithelium. This was significantly lower when compared to either neoplastic foci (P<0.0001) or nondysplastic Barrett's esophagus (P<0.0001) pre-photodynamic therapy. Notably, in four patients with post-photodynamic therapy recurrent neoplasia, cyclooxygenase-2 expression returned to elevated levels. Cyclooxygenase-2 expression is elevated in Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma prior to photodynamic therapy. Following successful photodynamic therapy, cyclooxygenase-2 expression in neosquamous epithelium returns to a low baseline level similar to that observed in native esophageal squamous epithelium. Post-photodynamic therapy neoplastic recurrence is associated with elevated cyclooxygenase-2 expression. Prospective studies should determine whether cyclooxygenase inhibitors have a role as adjuvant therapy to prevent recurrence of Barrett's esophagus following endoscopic therapy. PMID- 22081108 TI - Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation. AB - The XPD protein is a vital subunit of the general transcription factor TFIIH which is not only involved in transcription but is also an essential component of the eukaryotic nucleotide excision DNA repair (NER) pathway. XPD is a superfamily 2 5'-3' helicase containing an iron-sulphur cluster. Its helicase activity is indispensable for NER and it plays a role in the damage verification process. Here, we report the first structure of XPD from Thermoplasma acidophilum (taXPD) in complex with a short DNA fragment, thus revealing the polarity of the translocated strand and providing insights into how the enzyme achieves its 5'-3' directionality. Accompanied by a detailed mutational and biochemical analysis of taXPD, we define the path of the translocated DNA strand through the protein and identify amino acids that are critical for protein function. PMID- 22081107 TI - Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. AB - Eukaryotic chromosomes are replicated from multiple origins that initiate throughout the S-phase of the cell cycle. Why all origins do not fire simultaneously at the beginning of S-phase is not known, but two kinase activities, cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK), are continually required throughout the S-phase for all replication initiation events. Here, we show that the two CDK substrates Sld3 and Sld2 and their binding partner Dpb11, together with the DDK subunit Dbf4 are in low abundance in the budding yeast, Saccharomyces cerevisiae. Over-expression of these factors is sufficient to allow late firing origins of replication to initiate early and together with deletion of the histone deacetylase RPD3, promotes the firing of heterochromatic, dormant origins. We demonstrate that the normal programme of origin firing prevents inappropriate checkpoint activation and controls S-phase length in budding yeast. These results explain how the competition for limiting DDK kinase and CDK targets at origins regulates replication initiation kinetics during S-phase and establishes a unique system with which to investigate the biological roles of the temporal programme of origin firing. PMID- 22081109 TI - Inhibition of autophagy by TAB2 and TAB3. AB - Autophagic responses are coupled to the activation of the inhibitor of NF-kappaB kinase (IKK). Here, we report that the essential autophagy mediator Beclin 1 and TGFbeta-activated kinase 1 (TAK1)-binding proteins 2 and 3 (TAB2 and TAB3), two upstream activators of the TAK1-IKK signalling axis, constitutively interact with each other via their coiled-coil domains (CCDs). Upon autophagy induction, TAB2 and TAB3 dissociate from Beclin 1 and bind TAK1. Moreover, overexpression of TAB2 and TAB3 suppresses, while their depletion triggers, autophagy. The expression of the C-terminal domain of TAB2 or TAB3 or that of the CCD of Beclin 1 competitively disrupts the interaction between endogenous Beclin 1, TAB2 and TAB3, hence stimulating autophagy through a pathway that requires endogenous Beclin 1, TAK1 and IKK to be optimally efficient. These results point to the existence of an autophagy-stimulatory 'switch' whereby TAB2 and TAB3 abandon inhibitory interactions with Beclin 1 to engage in a stimulatory liaison with TAK1. PMID- 22081110 TI - Regulation of translocation polarity by helicase domain 1 in SF2B helicases. AB - Structurally similar superfamily I (SF1) and II (SF2) helicases translocate on single-stranded DNA (ssDNA) with defined polarity either in the 5'-3' or in the 3'-5' direction. Both 5'-3' and 3'-5' translocating helicases contain the same motor core comprising two RecA-like folds. SF1 helicases of opposite polarity bind ssDNA with the same orientation, and translocate in opposite directions by employing a reverse sequence of the conformational changes within the motor domains. Here, using proteolytic DNA and mutational analysis, we have determined that SF2B helicases bind ssDNA with the same orientation as their 3'-5' counterparts. Further, 5'-3' translocation polarity requires conserved residues in HD1 and the FeS cluster containing domain. Finally, we propose the FeS cluster containing domain also provides a wedge-like feature that is the point of duplex separation during unwinding. PMID- 22081111 TI - Synthetic biology approach to reconstituting the ubiquitylation cascade in bacteria. AB - Covalent modification of proteins with ubiquitin (Ub) is widely implicated in the control of protein function and fate. Over 100 deubiquitylating enzymes rapidly reverse this modification, posing challenges to the biochemical and biophysical characterization of ubiquitylated proteins. We circumvented this limitation with a synthetic biology approach of reconstructing the entire eukaryotic Ub cascade in bacteria. Co-expression of affinity-tagged substrates and Ub with E1, E2 and E3 enzymes allows efficient purification of ubiquitylated proteins in milligram quantity. Contrary to in-vitro assays that lead to spurious modification of several lysine residues of Rpn10 (regulatory proteasomal non-ATPase subunit), the reconstituted system faithfully recapitulates its monoubiquitylation on lysine 84 that is observed in vivo. Mass spectrometry revealed the ubiquitylation sites on the Mind bomb E3 ligase and the Ub receptors Rpn10 and Vps9. Forster resonance energy transfer (FRET) analyses of ubiquitylated Vps9 purified from bacteria revealed that although ubiquitylation occurs on the Vps9-GEF domain, it does not affect the guanine nucleotide exchanging factor (GEF) activity in vitro. Finally, we demonstrated that ubiquitylated Vps9 assumes a closed structure, which blocks additional Ub binding. Characterization of several ubiquitylated proteins demonstrated the integrity, specificity and fidelity of the system, and revealed new biological findings. PMID- 22081112 TI - Nausea and vomiting after breast cancer surgery, and relationship with tumor receptor status. AB - BACKGROUND: Breast surgery is associated with frequent post-operative nausea and vomiting (PONV). Studies have suggested that hormonal status affects PONV. Estrogen has been implicated in many emetic syndromes. Estrogen receptor (ER) and progesterone receptor (PR) status in breast tissue are hormonally affected. Kakugawa et al., in 2007, found a clear trend toward higher serum level of estrone, estradiol, and dehydroepiandrosterone sulfate in post menopausal women with PR-positive cancer. PURPOSE: To investigate the possibility of an association between ER and/or PR status of breast tumor and incidence of PONV after breast cancer surgery. METHODS: This observational study included 315 female patients undergoing major breast surgery. Relevant patient data, and intra operative and postoperative details were noted. Incidence of PONV was noted using the PONV score. Patients were divided into two age groups: less than or equal to 50 years and more than 50 years of age. The ER and/or PR status of the patient was unknown to the investigator until the final analysis. RESULTS: Use of the chi squared test revealed no association between ER and/or PR and total PONV. Patients below 50 years had higher incidence of total PONV (p = 0.023). In patients above 50 years, the incidence of PONV was higher in the ER-positive group (p = 0.018). CONCLUSION: The incidence of PONV is higher for patients below 50 years of age. The positive association between ER positivity and PONV in patients above 50 years of age could be attributed to the altered hormonal milieu in these patients and should be investigated further. PMID- 22081113 TI - Epidrum((r)): a new device to identify the epidural space with an epidural Tuohy needle. AB - Epidrum((r)) is an optimal pressure, loss of resistance device for identifying the epidural space. We investigated the usefulness of Epidrum versus the loss of resistance or hanging drop techniques while performing epidural anesthesia. Eighty adult patients who were scheduled for elective surgery under lumbar epidural anesthesia were randomized into two groups. The first group (Epidrum group) consisted of 40 adult patients who were scheduled for epidural anesthesia using Epidrum. The second group (control group) consisted of 40 adult patients who were scheduled for epidural anesthesia using the loss of resistance or hanging drop technique. We recorded the time required to identify the epidural space and outcomes of epidural catheterization. The attending anesthesiologists were also questioned regarding the ease of control of the Tuohy needle and of epidural space identification with each method. The time required to perform epidural anesthesia was significantly shorter in the Epidrum group than in the control group [28 s (10-76) vs. 90 s (34-185); median (interquartile range)] (p < 0.05). Tuohy needle control was significantly easier in the Epidrum group than in the control group (p < 0.05). Epidrum is useful for performing epidural anesthesia quickly while obtaining good Tuohy needle control. PMID- 22081114 TI - Utility of longitudinal paramedian view of ultrasound imaging for middle thoracic epidural anesthesia in children. AB - PURPOSE: The risk of nerve injury for pediatric thoracic epidural block increases stress for anesthesiologists. The purpose of this study was to investigate the usefulness of longitudinal ultrasound imaging for thoracic epidural block (T5-T6 or T6-T7) in anesthetized children scheduled for the Nuss procedure. METHODS: Neuraxial structure in the longitudinal paramedian section was observed using ultrasound imaging before epidural puncture (US group, n = 10). In the control group, usual epidural block without ultrasound was performed. Attempts were made to observe epidural catheterization in ultrasound imaging in three cases. RESULTS: Patient age ranged from 5 to 7 years. Time for epidural block in the US group [100 (77-116) s; median value (95% confidence interval)] was significantly shorter than that in the control group [165 (130-206) s; P = 0.001]. The difficulty score was significantly lower in the US group than in the control group (P < 0.001). Epidural catheterization was observed in all three cases in which the catheter manipulated the dura mater ventrally. There was a high correlation (r = 0.98, P < 0.001) between needle depth and ultrasound estimation of the skin-dura distance in the US group. CONCLUSION: We concluded that longitudinal paramedian ultrasound imaging could reduce performance time and the difficulty for anesthesiologists during epidural block. PMID- 22081115 TI - Patients' goals related to health and function in the first 13 months after allogeneic stem cell transplantation. AB - PURPOSE: Patient participation in goal setting and decision making is a core component of the rehabilitation process, but there is little information on what patients want to achieve after allogeneic stem cell transplantation (allo-SCT). The aim of this study was to describe adult patients' perceptions of goals related to health and function, as well as self-perceived limitations and facilitating strategies in the first 13 months after allo-SCT. METHODS: Fifteen patients with a median age of 44 years (range, 22-65 years) were interviewed on one occasion during the first year after allo-SCT. Data were analysed using qualitative content analysis. RESULTS: Results showed that patients felt that time after allo-SCT largely concerned: "to be healthy" and "to participate in a normal life". Some patients felt it was easy to set goals while others found it difficult. Most described goals had a long-term character. Patients were faced with a wide variety of limitations of which a few did not link to a described goal. Several facilitating strategies were described that either had or could help patients to reach their goals. CONCLUSIONS: Our results indicate that assistance with setting achievable goals, including individualised strategies and support from health care professionals to realise the goals, may assist in the rehabilitation to restore health and function after allo-SCT. PMID- 22081116 TI - Three-dimensional C-arm computed tomography reformation combined with fluoroscopic-guided sacroplasty for sacral metastases. AB - The aim of this retrospective study was to evaluate a sacroplasty technique, using three-dimensional C-arm CT reformation combined with fluoroscopic guidance for patients with severe painful sacral metastases. We studied the data of seven patients (average age 55.7 years) treated through trans-sacroiliac joint approach with the technique. Patients with additional thoracolumbar osteolytic metastases (five out of seven) also received concomitant vertebroplasty accordingly. Subjective significant pain relief was reported with visual analogue scale reduction >=4 in all seven patients at 1 month after procedure, six out of seven at 3 months, and five out of six at 6 months. Pain recurrence was reported in two patients at 3 and 6 months follow-up, respectively, associated with their clinical evidence of tumor progression. One patient died from underlying disease unrelated with the procedure. Sacroplasty under three-dimensional C-arm CT reformation combined with fluoroscopic guidance was a feasible, safe, and minimally invasive procedure that could provide both the precise control of needle placement and cement injection with one imaging system. PMID- 22081117 TI - Gastrointestinal symptoms after pelvic radiotherapy: a national survey of gastroenterologists. AB - PURPOSE: Seventeen thousand patients receive treatment with radical pelvic radiotherapy annually in the UK. Up to 50% develop significant gastrointestinal symptoms. The National Cancer Survivorship Initiative has identified access to specialist medical care for those with complications after cancer as one of their four key needs. We aimed to determine the current practice of British gastroenterologists with regards to chronic gastrointestinal symptoms after pelvic radiotherapy. METHODS: A questionnaire was developed and sent up to a maximum of five times to all UK consultant gastroenterologists. RESULTS: Eight hundred sixty-six gastroenterologists were approached and 165 (20%) responded. Sixty-one percent saw one to four patients annually with bowel symptoms after radiotherapy. Eighteen percent rate the current treatments as effective "often" or "most of the time". Forty-seven percent of gastroenterologists consider themselves "confident with basic cases", with 11% "confident in all cases". Fifty nine percent thinks a gastroenterologist with a specialist interest should manage these patients. Although only 29% thinks a specific service is required for these patients, 34% rates the current service as inadequate. The ideal service was considered to be gastroenterology-led, multidisciplinary and regional. Low referral rates, poor evidence-base and poor funding are cited as reasons for the current patchy services. CONCLUSIONS: The low response rate contrasts with that from a parallel survey of clinical oncologists. This may reflect the opinion that radiation-induced bowel toxicity is not a significant issue, which may be because only a small proportion of patients are referred to gastroenterologists. The development of new, evidence-based gastroenterology-led services is considered the optimal way to meet the needs of these patients. PMID- 22081118 TI - The effects on pain and activity of daily living caused by crusted exudation in patients with head and neck cancer treated with cetuximab and radiotherapy. AB - PURPOSE: To date, the specific role of "in-field" crusting exudation on pain and on activity of daily living (ADL) in head and neck cancer (HNSCC) patients undergoing treatment with cetuximab and radiochemotherapy has been neglected. The purpose of the study was to evaluate the role of crusting exudation on the severity of pain and ADL METHODS: Thirty-seven of the 45 HNSCC patients enrolled in the alternating radiotherapy, chemotherapy, and cetuximab trial were evaluated in this study. The main radiodermatitis signs (the intensity of erythema, the extension of dry, and moist desquamation and of necrosis)--including crusting exudation severity--pain, ADL, and radiodermatitis scores were registered at least weekly during and after treatment. The correlation between crusting exudation and pain or ADL was evaluated. RESULTS: The "in-field" crusting exudation score seemed to have the strongest correlation with pain (Spearman's rho = 0.897; p < 0.001) and the most intense influence on it (Co-B = 0.715; 95% C.I. = 0.643-0.787). However, it seemed to have a weaker correlation with ADL than the other clinical radiodermatitis signs. CONCLUSIONS: Crusts have the strongest correlation with pain in patients with Cetuximab-related radiation dermatitis. Moreover, the presence of crusts can lead operators to misclassify dermatitis as score 4, causing unnecessary delays or interruptions in treatment. PMID- 22081119 TI - Do patients' information needs decrease over the course of radiotherapy? AB - PURPOSE: We aimed to investigate if cancer patients' information needs decrease during radiotherapy and if so, which patient, consultation and radiation oncologist characteristics are associated with a decrease in information needs over time. METHODS: In this longitudinal study, patients (n = 104) completed a baseline questionnaire a week before the initial radiotherapy consultation, immediately following this initial consultation, and 1 week prior to the first follow-up visit, which took place on average 3-5 weeks after the initial visit. Besides information needs, measured by the Information Preference for Radiotherapy Patients scale, the questionnaire assessed patient, consultation and radiation oncologist characteristics. RESULTS: Information needs decreased over time, but remained at a high level. Being religious, being male, having low health literacy and higher perceived involvement during the consultation were all statistically significantly associated to a decrease in information needs on specific domains (e.g. procedures or side effects). CONCLUSIONS: Cancer patients' information needs decline between the initial consultation and the first follow up visit, but remain high. It is therefore advised to investigate the patients' information needs at every radiotherapy visit and not rely on giving information just once. Furthermore, radiation oncologists should check if the information given at first consultation is understood and remembered. By those means, tailored information giving becomes possible. PMID- 22081120 TI - Nanosphere templated metallic grating assisted enhanced fluorescence. AB - In this paper, enhanced fluorescence from a silver film coated nanosphere templated grating is presented. Initially, numerical simulation was performed to determine the plasmon resonance wavelength by varying the thickness of the silver film on top of a monolayer of 400 nm nanospheres. The simulation results are verified experimentally and tested for enhancing fluorescence from fluorescein isothiocyanate whose excitation wavelength closely matches with the plasmon resonance wavelength of the substrate with 100 nm silver film over nanosphere. The 12 times enhancement in the intensity is attributed to the local field enhancement in addition to the excitation of surface plasmon polaritons along the surface. PMID- 22081122 TI - Neuromuscular electrical stimulation versus traditional therapy in patients with Parkinson's disease and oropharyngeal dysphagia: effects on quality of life. AB - This study compares the effects of traditional logopedic dysphagia treatment with those of neuromuscular electrical stimulation (NMES) as adjunct to therapy on the quality of life in patients with Parkinson's disease and oropharyngeal dysphagia. Eighty-eight patients were randomized over three treatment groups. Traditional logopedic dysphagia treatment and traditional logopedic dysphagia treatment combined with NMES at sensor or motor level stimulation were compared. At three times (pretreatment, post-treatment, and 3 months following treatment), two quality-of-life questionnaires (SWAL-QOL and MD Anderson Dysphagia Inventory) and a single-item Dysphagia Severity Scale were scored. The Functional Oral Intake Scale was used to assess the dietary intake. After therapy, all groups showed significant improvement on the Dysphagia Severity Scale and restricted positive effects on quality of life. Minimal group differences were found. These effects remained unchanged 3 months following treatment. No significant correlations were found between dietary intake and quality of life. Logopedic dysphagia treatment results in a restricted increased quality of life in patients with Parkinson's disease. In this randomized controlled trial, all groups showed significant therapy effects on the Dysphagia Severity Scale and restricted improvements on the SWAL-QOL and the MDADI. However, only slight nonsignificant differences between groups were found. PMID- 22081121 TI - Protective potential of MMR vaccine against complete Freund's adjuvant-induced inflammation in rats. AB - The aim of the present study was to investigate the effect of MMR vaccine on inflammation which was induced by complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. Rats were randomly divided into the control, CFA, MMR and CFA + MMR groups. Inflammatory symptoms such as paw oedema was measured in CFA injected rats' paw. Body weight changes and alterations in some haematological parameters and oxidative stress markers following CFA injection were checked. In CFA-inflammed rats, there was a significant increase in rat paw thickness and decrease in body weight increment. MMR exhibited a significant anti-inflammatory effect as manifested by reduction in paw thickness and normal gain in body weight when administered 1 week prior to induction of inflammation. The altered haematological parameters (TLC) and oxidative stress markers (MDA, GSH, SOD) in the inflammed rats were significantly brought back to near normal by MMR treatment. In conclusion, MMR vaccine showed a reduction in rat paw thickness and it could significantly normalize the haematological and biochemical abnormalities in CFA-induced inflammatory pain model in rats. Our data suggested that MMR could be a potential protective agent against certain types of inflammatory pain. Further histopathological and radiological studies are required to confirm the possibility of developing novel therapeutic vaccines against some forms of arthritis. PMID- 22081123 TI - Study of the reaction 2-(p-nitrophenyl)ethyl bromide + OH- in dimeric micellar solutions. AB - The dehydrobromination reaction 2-(p-nitrophenyl)ethyl bromide + OH- was investigated in several alkanediyl-alpha-omega-bis(dodecyldimethylammonium) bromide, 12-s-12,2Br- (with s = 2, 3, 4, 5, 6, 8, 10, 12) micellar solutions, in the presence of NaOH 5 * 10-3 M. The kinetic data were quantitatively rationalized within the whole surfactant concentration range by using an equation based on the pseudophase ion-exchange model and taking the variations in the micellar ionization degree caused by the morphological transitions into account. The agreement between the theoretical and the experimental data was good in all the dimeric micellar media studied, except for the 12-2-12,2Br- micellar solutions. In this case, the strong tendency to micellar growth shown by the 12-2 12,2Br- micelles could be responsible for the lack of accordance. Results showed that the dimeric micelles accelerate the reaction more than two orders of magnitude as compared to water. PMID- 22081124 TI - Sonomyographic responses during voluntary isometric ramp contraction of the human rectus femoris muscle. AB - This paper aims to investigate the relationship between torque and muscle morphological change, which is derived from ultrasound image sequence and termed as sonomyography (SMG), during isometric ramp contraction of the rectus femoris (RF) muscle, and to further compare SMG with the electromyography (EMG) and mechanomyography (MMG), which represent the electrical and mechanical activities of the muscle. Nine subjects performed isometric ramp contraction of knee up to 90% of the maximal voluntary contraction (MVC) at speeds of 45, 22.5 and 15% MVC/s, and EMG, MMG and ultrasonography were simultaneously recorded from the RF muscle. Cross-sectional area, which was referred to as SMG, was automatically extracted from continuously captured ultrasound images using a newly developed image tracking algorithm. Polynomial regression analyses were applied to fit the EMG/MMG/SMG-to-torque relationships, and the regression coefficients of EMG, MMG, and SMG were compared. Moreover, the effect of contraction speed on SMG/EMG/MMG to-torque relationships was tested by pair-wise comparisons of the mean relationship curves at different speeds for EMG, MMG and SMG. The results show that continuous SMG could provide important morphological parameters of continuous muscle contraction. Compared with EMG and MMG, SMG exhibits different changing patterns with the increase of torque during voluntary isometric ramp contraction, and it is less influenced by the contraction speed. PMID- 22081125 TI - Change of muscle activation patterns in uphill cycling of varying slope. AB - In the present study, we quantitatively described and compared lower extremity neuromuscular patterns during level cycling (LC), 10 and 20% uphill cycling (UC). We hypothesized that both the timing and intensity of activity of selected lower extremity muscles will differ between steep (but not moderate slope) UC condition and LC. Twelve trained mountain bikers performed an experimental test with three different cycling conditions (level, 10% slope and 20% slope) with EMG monitoring of eight lower extremity muscles. Significant changes (p < 0.05) in muscle activation timing during 20% UC compared to LC (15 degrees later onset and 39 degrees earlier offset) were observed in m. rectus femoris (RF). Range of activity during 20% UC compared to LC was also significantly (p < 0.05) modified in m. vastus medialis, m. vastus lateralis (8 degrees and 5 degrees shorter) and m. biceps femoris (BF; 17 degrees longer). Furthermore, a reduction of EMG activity level was observed for RF and m. tibialis anterior (TA) during 20% UC compared to LC (25 and 19%; p < 0.05), while the opposite effect was observed for m. gluteus maximus (GM; 12%; p < 0.05). Peak cross-correlation coefficients in all cycling conditions for all muscles were high (all coefficients >= 0.83). We have shown that altered body orientation during steep, but not moderate, slope UC significantly modified the timing and intensity of several lower extremity muscles, the most affected being those that cross the hip joint and TA. The observed modifications in neuromuscular patterns during 20% UC could have a significant effect on lower extremity joint kinetics and cycling efficiency. PMID- 22081126 TI - Cyanine fluorophore derivatives with enhanced photostability. AB - Fluorescence applications requiring high photostability often depend on the use of solution additives to enhance fluorophore performance. Here we demonstrate that the direct or proximal conjugation of cyclooctatetraene (COT), 4-nitrobenzyl alcohol (NBA) or Trolox to the cyanine fluorophore Cy5 dramatically enhanced fluorophore photostability without otherwise affecting its native spectral characteristics. Such conjugation is a powerful means of improving the robustness of fluorescence-based applications demanding long-lived, nonblinking fluorescence emission. PMID- 22081127 TI - Embryonic stem cell-based mapping of developmental transcriptional programs. AB - The study of developmentally regulated transcription factors by chromatin immunoprecipitation and deep sequencing (ChIP-seq) faces two major obstacles: availability of ChIP-grade antibodies and access to sufficient number of cells. We describe versatile genome-wide analysis of transcription-factor binding sites by combining directed differentiation of embryonic stem cells and inducible expression of tagged proteins. We demonstrate its utility by mapping DNA-binding sites of transcription factors involved in motor neuron specification. PMID- 22081128 TI - Mechanism of nanoparticle actuation by responsive polymer brushes: from reconfigurable composite surfaces to plasmonic effects. AB - The mechanism of nanoparticle actuation by stimuli-responsive polymer brushes triggered by changes in the solution pH was discovered and investigated in detail in this study. The finding explains the high spectral sensitivity of the composite ultrathin film composed of a poly(2-vinylpyridine) (P2VP) brush that tunes the spacing between two kinds of nanoparticles-gold nanoislands immobilized on a transparent support and gold colloidal particles adsorbed on the brush. The optical response of the film relies on the phenomenon of localized surface plasmon resonances in the noble metal nanoparticles, giving rise to an extinction band in visible spectra, and a plasmon coupling between the particles and the islands that has a strong effect on the band position and intensity. Since the coupling is controlled by the interparticle spacing, the pH-triggered swelling shrinking transition in the P2VP brush leads to pronounced changes in the transmission spectra of the hybrid film. It was not established in the previous publications how the actuation of gold nanoparticles within a 10-15 nm interparticle distance could result in the 50-60 nm shift in the absorbance maximum in contrast to the model experiments and theoretical estimations of several nanometer shifts. In this work, the extinction band was deconvoluted into four spectrally separated and overlapping contributions that were attributed to different modes of interactions between the particles and the islands. These modes came into existence due to variations in the thickness of the grafted polymeric layer on the profiled surface of the islands. In situ atomic force microscopy measurements allowed us to explore the behavior of the Au particles as the P2VP brush switched between the swollen and collapsed states. In particular, we identified an interesting, previously unanticipated regime when a particle position in a polymer brush was switched between two distinct states: the particle exposed to the surface of the collapsed layer and the particle engulfed by the swollen brush. On average, the characteristic distance between the particles and the islands increased upon the brush swelling. The observed behavior was a result of the anchoring of the particles to polymeric chains that limited the particles' vertical motion range. The experimental findings will be used to design highly sensitive optical nanosensors based on a polymer-brush modulated interparticle plasmon coupling. PMID- 22081129 TI - Laboratory testing of anticoagulants: the present and the future. AB - This review provides an update on laboratory testing and monitoring for existing and emerging anticoagulants, starting with an overview of haemostasis and the routine coagulation tests currently employed within most haemostasis laboratories, including the prothrombin time (PT)/international normalised ratio (INR) and the activated partial thromboplastin time (APTT). Current anticoagulant therapy and laboratory monitoring is then discussed in terms of benefits and limitations, followed by a similar brief discussion of the new and emerging anticoagulants. The main focus, however, is laboratory testing related to vitamin K antagonists, heparin, lepirudin and the new agents dabigatran etexilate and rivaroxaban. Although the newer agents do not require laboratory monitoring, laboratory testing will occasionally be required, and pathology laboratories should become proactive in developing appropriate strategies. The tests most likely to fulfill this role are the ecarin clotting time (or chromogenic alternatives), and the chromogenic anti-Xa assay. Nevertheless, the dilute Russell viper venom time (dRVVT) assay may provide another alternative, and existing routine tests are also likely to be utilised for the foreseeable future, potentially also for laboratory testing of the new anticoagulants, albeit perhaps in modified form. PMID- 22081130 TI - Activation of beta-catenin is a late event in the pathogenesis of nephroblastomas and rarely correlated with genetic changes of the APC gene. AB - AIMS: Activation of beta-catenin has been identified as a possible mechanism for the development of nephroblastomas. In our study we investigated whether this activation occurs already in precursor lesions of nephroblastomas, called nephrogenic rests (NRs). Inactivation of the adenomatous polyposis coli (APC) protein is an important regulatory mechanism of activating beta-catenin. We clarified the role of APC by assessing loss of heterozygosity (LOH) and possible mutations within the genomic region. METHODS: Activation of beta-catenin was examined by immunohistochemistry identifying nuclear translocation. Two polymorphic loci of the APC gene were investigated for LOH and sequence analysis was performed for the mutation cluster region of the APC gene on formalin fixed, paraffin embedded samples. RESULTS: Four of the 18 nephroblastomas available for immunohistochemistry exhibited nuclear staining of beta-catenin, but none of the NRs. Analysis of LOH revealed 14 homozygous samples, 10 heterozygous tumours and six tumours exhibiting LOH of the APC gene. One blastema-type nephroblastoma showed nuclear localisation of beta-catenin in conjunction with LOH of the APC gene. Analysis of 12 nephroblastomas revealed no sequence aberration. CONCLUSION: Our results indicate that nuclear activation of beta-catenin is a late event in the tumorigenesis of nephroblastomas coinciding in some tumours with LOH of the APC gene. PMID- 22081131 TI - SLP-2 overexpression could serve as a prognostic factor in node positive and HER2 negative breast cancer. AB - AIMS: This study aimed to evaluate the utility as a prognostic factor of SLP-2 on the outcome of breast cancer patients. METHODS: We performed immunohistochemical analysis to examine the SLP-2 expression in a large panel of invasive breast cancer samples. RESULTS: Of the 496 samples, 261 showed overexpression of SLP-2. Importantly, there were significant associations between SLP-2 overexpression and tumour size (p = 0.002), lymph node/distant metastases, clinical stage (p < 0.001), HER2/neu expression (p = 0.003). In addition, there were obvious differences in levels of SLP-2 expression within four molecular subtypes of breast cancer (p = 0.011). High level SLP-2 expression was shown in tumour samples of HER2 and luminal B subtypes, and low level SLP-2 expression was shown in luminal A and triple negative subtypes, suggesting that overexpression of SLP 2 was closely correlated with HER2/neu expression, and that both SLP-2 and HER2/neu can play a role in lymph node/distant metastases of breast cancers. Thus lymph node status, HER2/neu and SLP-2 high-level expression can act as independent prognostic factors. CONCLUSIONS: There is an obvious link between SLP 2 and HER2/neu expression. Overexpression of SLP-2 is associated with poorer total survival, especially in lymph node positive coupled with HER2/neu negative patients. PMID- 22081132 TI - Mutational analysis of tumour suppressor gene NF2 in common solid cancers and acute leukaemias. AB - AIMS: Germline mutation of NF2 gene is a feature of neurofibromatosis type 2 familial cancer syndrome. Also, somatic point mutations of NF2 mutation have been reported in tumours originated from nerve structures. A recent study revealed that NF2 gene was mutated in renal cell carcinoma (RCC) as well, suggesting a possibility that NF2 gene might be somatically mutated in other human cancers. The aim of this study was to explore whether NF2 genes are somatically mutated, and contribute to tumorigenesis in common human cancers. METHODS: For this, we analysed the entire coding region of NF2 gene in 45 colorectal carcinomas, 45 gastric, 45 breast, 45 lung, 45 hepatocellular (HCC), 45 prostate carcinomas, and 45 acute leukaemias by a single-strand conformation polymorphism assay. RESULTS: Overall, we found NF2 mutations in one HCC (1/45; 2.2%) (hepatitis B virus related HCC), one lung carcinoma (1/45; 2.2%) (squamous cell carcinoma), and one acute leukaemia (1/45; 2.2%) (acute myelogenous leukaemia minimally differentiated). All of the mutations were missense mutations that would substitute amino acids in the NF2 protein (p.A238 V, p.A451T and p.R467K). CONCLUSION: Our data indicate that somatic mutation of NF2 gene is not prevalent in common human cancers, and its mutation somatically occurs in a minor fraction of HCC, lung cancer and acute leukaemia. These data suggest that somatic mutation of NF2 tumour suppressor gene may not play a central role in development of common cancers. PMID- 22081133 TI - 3-Glycidoxypropyltrimethoxysilane mediated in situ synthesis of noble metal nanoparticles: application to hydrogen peroxide sensing. AB - The in situ synthesis is reported of noble metal nanoparticles via 3 glycidoxypropyltrimethoxysilane mediated reduction of 3 aminopropyltrimethoxysilane treated metal salts during sol-gel processing. The method described involves the synthesis of uniform spherical nanoparticles of gold, silver and palladium with controlled size that can be directly utilized for thin film preparation. A detailed study of the synthesis and application of gold nanoparticles to the electrochemical detection of hydrogen peroxide was carried out and reveals that the amplification of hydrogen peroxide sensing is size dependent. In addition, these nanoparticles exhibit excellent compatibility towards composite preparation. As an example, a nanocomposite with Prussian Blue (PB) is synthesized and found to be useful for the fabrication of chemically modified electrodes (CME). The resulting CME shows dramatic improvement in the electrochemistry of PB with gradual enhancement in electrocatalytic efficiency towards hydrogen peroxide sensing. The nanocomposite is used to study the direct and horseradish peroxidase (HRP)-catalyzed reduction of hydrogen peroxide. The results recorded for hydrogen peroxide analysis show an improvement in sensitivity and limit of detection on decreasing the size of gold nanoparticles in all cases. PMID- 22081134 TI - Properties of L-type bovine spongiform encephalopathy in intraspecies passages. AB - The origin and transmission routes of atypical bovine spongiform encephalopathy (BSE) remain unclear. To assess whether the biological and biochemical characteristics of atypical L-type BSE detected in Japanese cattle (BSE/JP24) are conserved during serial passages within a single host, 3 calves were inoculated intracerebrally with a brain homogenate prepared from first-passaged BSE/JP24 affected cattle. Detailed immunohistochemical and neuropathologic analysis of the brains of second-passaged animals, which had developed the disease and survived for an average of 16 months after inoculation, revealed distribution of spongiform changes and disease-associated prion protein (PrP(Sc)) throughout the brain. Although immunolabeled PrP(Sc) obtained from brain tissue was characterized by the presence of PrP plaques and diffuse synaptic granular accumulations, no stellate-type deposits were detected. Western blot analysis suggested no obvious differences in PrP(Sc) molecular mass or glycoform pattern in the brains of first- and second-passaged cattle. These findings suggest failures to identify differences in mean incubation period and biochemical and neuropathologic properties of the BSE/JP24 prion between the first and second passages in cattle. PMID- 22081135 TI - Spatial distribution of putative growth factors in the guinea pig placenta and the effects of these factors, plasma, and bile on the growth and chemotaxis of Campylobacter jejuni. AB - The pregnant guinea pig is an effective model for studying abortifacient Campylobacter spp, and previous experiments have demonstrated that C. jejuni IA3902 has a marked predilection for the subplacenta while sparing the placental disc in this species. In the study described here, the growth and chemotaxis of IA3902 and a reference strain (NCTC 11168) are compared in the presence of subplacental and placental factors, as well as bile and plasma, from pregnant and nonpregnant guinea pigs. Both strains grew better in subplacental versus placental disc tissue extracts at 24 hours; however, only IA3902 maintained this enhancement at 48 hours. Histochemistry and lectin histochemistry were used to localize mucin, iron, and l-fucose within the placental unit. Mucin was most abundant in subplacental lacunae, the junctional zone, and visceral yolk sac placenta, while iron was most abundant in the placental disc, and L-fucose containing surface glycans were limited to the visceral yolk sac placenta. These 3 individual factors, along with progesterone and estradiol, were evaluated for effects on growth and chemotaxis of C. jejuni. Mucin, iron, and L-fucose were growth promoting, while l-fucose was also chemoattractive for both strains. Progesterone, estradiol, and pregnant guinea pig plasma did not affect growth or chemotaxis, and no difference was observed when bile from pregnant and nonpregnant animals was compared. These findings demonstrate the presence of specific factors within the guinea pig placental unit that drive chemotaxis and enhance growth of C. jejuni, shedding light on potential mechanisms underlying the fetoplacental tropism observed with this strain. PMID- 22081136 TI - P/S ligands derived from carbohydrates in Rh-catalyzed hydrosilylation of ketones. AB - Reported is the synthesis of a number of diastereomerically pure cationic Rh(I) complexes I starting from phosphinite thioglycosides. These complexes were used in the asymmetric hydrosilylation of prochiral ketones. The reactivity and enantioselectivity of the reaction was shown to be dependent on the pyranose ring, the substituent at the sulfur atom, the hydroxylic protective groups and most significantly on the alkene co-ligand. PMID- 22081137 TI - Profilin1 is required for glial cell adhesion and radial migration of cerebellar granule neurons. AB - Cerebellar granule neurons (CGNs) exploit Bergmann glia (BG) fibres for radial migration, and cell-cell contacts have a pivotal role in this process. Nevertheless, little is known about the mechanisms that control CGN-BG interaction. Here we demonstrate that the actin-binding protein profilin1 is essential for CGN-glial cell adhesion and radial migration. Profilin1 ablation from mouse brains leads to a cerebellar hypoplasia, aberrant organization of cerebellar cortex layers and ectopic CGNs. Conversely, neuronal progenitor proliferation, tangential migration of neurons and BG morphology appear to be independent of profilin1. Our mouse data and the mapping of developmental neuropathies to the chromosomal region of PFN1 suggest a similar function for profilin1 in humans. PMID- 22081138 TI - Teaching and textbooks by Jacobs Howy. PMID- 22081139 TI - Protein synthesis and translational control: at eye level with the ribosome. AB - At the EMBO Conference on 'Protein Synthesis and Translational Control' held in Heidelberg in September 2011, scientists shared their latest findings on the structure and function of the ribosome, mRNA-specific regulation of translation and the numerous quality control mechanisms that ensure accurate protein synthesis. PMID- 22081140 TI - Dictyostelium chemotaxis: essential Ras activation and accessory signalling pathways for amplification. AB - Central to chemotaxis is the molecular mechanism by which cells exhibit directed movement in shallow gradients of a chemoattractant. We used Dictyostelium mutants to investigate the minimal requirements for chemotaxis, and identified a basal signalling module providing activation of Ras at the leading edge, which is sufficient for chemotaxis. The signalling enzymes PI3K, TorC2, PLA2 and sGC are not required for Ras activation and chemotaxis to folate or to steep gradients of cAMP, but they provide a memory of direction and improved orientation of the cell, which together increase the sensitivity about 150-fold for chemotaxis in shallow cAMP gradients. PMID- 22081141 TI - Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. AB - The protein PCSK9 (proprotein convertase subtilisin/kexin type 9) is a key regulator of low-density lipoprotein receptor (LDLR) levels and cardiovascular health. We have determined the crystal structure of LDLR bound to PCSK9 at neutral pH. The structure shows LDLR in a new extended conformation. The PCSK9 C terminal domain is solvent exposed, enabling cofactor binding, whereas the catalytic domain and prodomain interact with LDLR epidermal growth factor(A) and beta-propeller domains, respectively. Thus, PCSK9 seems to hold LDLR in an extended conformation and to interfere with conformational rearrangements required for LDLR recycling. PMID- 22081143 TI - A new target for personalized medicine. PMID- 22081142 TI - Superinfection in malaria: Plasmodium shows its iron will. AB - After the bite of a malaria-infected mosquito, the Plasmodium sporozoite infects liver cells and produces thousands of merozoites, which then infect red blood cells, causing malaria. In malaria-endemic areas, several hundred infected mosquitoes can bite an individual each year, increasing the risk of superinfection. However, in infants that are yet to acquire immunity, superinfections are infrequent. We have recently shown that blood-stage parasitaemia, above a minimum threshold, impairs the growth of a subsequent sporozoite infection of liver cells. Blood-stage parasites stimulate the production of the host iron-regulatory factor hepcidin, which redistributes iron away from hepatocytes, reducing the development of the iron-dependent liver stage. This could explain why Plasmodium superinfection is not often found in young nonimmune children. Here, we discuss the impact that such protection from superinfection might have in epidemiological settings or in programmes for controlling malaria, as well as how the induction of hepcidin and redistribution of iron might influence anaemia and the outcome of non-Plasmodium co-infections. PMID- 22081144 TI - CD8alphaalpha and -alphabeta isotypes are equally recruited to the immunological synapse through their ability to bind to MHC class I. AB - Bimolecular fluorescence complementation was used to engineer CD8 molecules so that CD8alphaalpha and CD8alphabeta dimers can be independently visualized on the surface of a T cell during antigen recognition. Using this approach, we show that CD8alphaalpha is recruited to the immunological synapse almost as well as CD8alphabeta, but because the kinase Lck associates preferentially with CD8alphabeta in lipid rafts, CD8alphaalpha is the weaker co-receptor. During recognition of the strong CD8alphaalpha ligand H2-TL, CD8alphaalpha is preferentially recruited. Thus, recruitment of the two CD8 species correlates with their relative binding to the available ligands, rather than with the co receptor functions of the CD8 species. PMID- 22081146 TI - Keratometry evaluations with the Pentacam high resolution in comparison with the automated keratometry and conventional corneal topography. AB - PURPOSE: To determine the reliability and repeatability of keratometry (K) measurements obtained with the Pentacam high resolution (HR), automated keratometry, and corneal topography systems. METHODS: The right eyes of 46 healthy subjects were examined prospectively. Keratometry measurements in the flat (Kf) and steep (Ks) meridians were taken by 2 independent investigators with the Pentacam HR (Oculus, Wetzlar, Germany) followed by automated keratorefractometry (KR-8100; Topcon, Tokyo, Japan), and corneal topography (TMS 4; Tomey, Erlangen, Germany). RESULTS: The mean K readings of the Pentacam HR, automated keratometry, and corneal topography were 43.40/43.34 diopter (D), 43.99/43.98 D, and 43.80/43.83 D, respectively. The difference between the values was statistically significant (P < 0.0001, repeated measures analysis of variance). Strong significant correlation was observed between the Pentacam HR and keratometry (Kf: r = 0.952/0.954; Ks: r = 0.845, Spearman rank test), and Pentacam HR and corneal topography (Kf: r = 0.933/0.930; Ks: r = 0.838/0.829) (P < 0.0001). No significant difference was presented between the 2 investigators for any of the instruments (P = 0.215-0.983). Moreover, high correlation was found between the K readings of the observers (interoperator intraclass correlation coefficients ranged from 0.95 to 0.99). CONCLUSIONS: The Pentacam HR provided reliable K measurements in clinical practice in comparison with an automated keratometer and a corneal topographer. Based on the results, for patient follow-up, one keratometry device is recommended. PMID- 22081145 TI - Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients. AB - The aim of this dual-isotope SPECT imaging study was to evaluate striatal dopamine transporter (DAT) and D2 receptor availability in first-episode never treated and haloperidol-treated schizophrenic patients and whether the availability is associated with psychopathology. Twenty-four inpatients with a first acute schizophrenic episode were enrolled in the study; 12 of these patients were treated with haloperidol for 2 weeks before dual-isotope SPECT was performed, whereas the other 12 patients underwent the SPECT evaluation directly after enrollment. Twelve healthy control persons were also recruited and evaluated with the dual-isotope SPECT protocol. Psychopathology was assessed by the Positive and Negative Syndrome Scale and other scales. D2-radioligand binding did not differ between drug-naive patients and the control group but was significantly lower in the haloperidol-treated group. DAT availability was also significantly lower in the haloperidol patients than in the other two groups and differed significantly between drug-naive, positive-syndrome-type patients and healthy controls. The data obtained with the new dual-isotope SPECT technique reveal a direct effect of haloperidol at the D2 and DAT receptor level. PMID- 22081147 TI - Microkeratome-assisted superficial anterior lamellar keratoplasty for anterior stromal corneal opacities after penetrating keratoplasty. AB - PURPOSE: To describe the surgical technique and report the outcomes of patients treated with microkeratome-assisted superficial anterior lamellar keratoplasty for anterior stromal corneal opacities developing after penetrating keratoplasty (PK). METHODS: All patients with post-penetrating keratoplasty anterior stromal opacities treated with microkeratome-assisted superficial anterior lamellar keratoplasty between July 2005 and June 2007 were reviewed. A 130-MUm superficial keratectomy was performed, followed by the placement of an appropriately sized donor graft, which was secured with overlay sutures. Refraction, corneal topography, and uncorrected and best-corrected visual acuities (UCVA, BCVA, respectively) were noted at each examination. RESULTS: Nine eyes of 8 consecutive patients were identified. Causes of anterior stromal opacities included dystrophy recurrence (n = 3), post-photorefractive keratectomy haze (n = 2), and scarring after stromal melt (n = 4). BCVA improved in all 9 eyes at final follow-up, and 7 of 9 eyes achieved >=20/40 within the first month. Average follow-up period was 28 +/- 3.9 months. Refractive astigmatism also improved by an average of 0.7 diopters. CONCLUSIONS: Superficial anterior lamellar keratoplasty is a viable and effective alternative to repeat PK in treating anterior stromal scars. It avoids open-globe surgery and exposure to endothelial rejection associated with repeat PK, and visual rehabilitation is considerably quicker. PMID- 22081148 TI - Intradescemetic air bubble trapping during deep anterior lamellar keratoplasty. AB - We describe a case of a 52-year-old man in whom the appearance of an air bubble developed, trapped within the Descemet membrane (DM), that occurred during a planned deep anterior lamellar keratoplasty using the "big bubble" technique. This situation can occur because Descemet membrane's anatomic structure can be opened by the gas dissection; this complication may result in unanticipated results during and after this type of surgery. Surgeons should be aware of this specific risk, so they will recognize it when it occurs. Optical coherence tomography (OCT) imaging and surgical management are presented. PMID- 22081149 TI - Small-incision Descemet stripping automated endothelial keratoplasty: a comparison of small-incision tissue injector and forceps techniques. AB - PURPOSE: To describe a novel, small-incision, no-fold Descemet stripping automated endothelial keratoplasty (DSAEK) graft injector and to compare complications, visual acuity, and endothelial cell loss with a forceps technique. METHODS: An Institutional Review Board-approved, interventional, nonrandomized, consecutive case series analysis of 175 eyes undergoing DSAEK for Fuchs dystrophy and bullous keratopathy. The injector arm is prospective, and the forceps arm is retrospective. Seventy grafts were performed with a DSAEK graft injector, and 105 grafts were performed using a small-incision forceps technique. Preoperative and postoperative visual acuities at 3 and 6 months, 6-month endothelial cell counts, and complications, including graft dislocation, failure, and rejection, were recorded. Fifty-seven of 232 eyes met exclusion criteria for previous incisional corneal or glaucoma surgery. RESULTS: There were 4 eyes (5.7%) in the injector group and 29 eyes (27.6%) in the forceps group that required a re-bubble procedure because of graft detachment. One graft (1.4%) failed in the injector group and 7 grafts (6.5%) failed in the forceps group. Excluding eyes with other ocular comorbidities (43), in the injector group 74% were 20/40 or better at 6 months and 100% were 20/60 or better. In the forceps group, 72% were 20/40 or better at 6 months and 98% were 20/60 or better. Six-month postoperative endothelial cell counts were available for 84 (46 injector and 38 forceps) eyes, with an average cell loss of 28.3% in the injector group and 44.1% in the forceps group. CONCLUSIONS: DSAEK is an effective treatment of endothelial dysfunction. Surgical technique is important to limit endothelial cell loss and prevent complications, such as graft dislocation. The injector device has several advantages over the trifold forceps technique, including decreased endothelial cell loss, graft dislocation rate, and graft failure rate, and it reduces the DSAEK learning curve. DSAEK graft injectors likely will have a role in the future of endothelial keratoplasty. PMID- 22081150 TI - Randomized controlled trial of subconjunctival bevacizumab injection in impending recurrent pterygium: a pilot study. AB - PURPOSE: To investigate the efficacy and safety of subconjunctival bevacizumab injection for the treatment of impending recurrent pterygium. METHODS: A prospective, randomized, single-masked, controlled trial was conducted in 80 patients with impending recurrent pterygium. Patients were randomized into 4 groups using random tables: 20 patients served as a control and treatment groups received a single intralesional injection of 1.25 mg (20 patients, group 1), 2.5 mg (20 patients, group 2), or 3.75 mg (20 patients, group 3) of bevacizumab. Topical 0.1% fluorometholone and ocular lubricant were administered 4 times daily for 1 month in all groups. Severity of impending recurrent pterygium graded by photographic assessment (at baseline, 3 days, 1 week, and 2, 4, 8, and 12 weeks after treatment) and true recurrence were the main outcome measures. RESULTS: At 3 days, the conjunctival injection significantly decreased in all treatment groups (P < 0.01). A significant decrease in the conjunctival injection was still observed until 2 and 4 weeks in only groups 2 and 3, respectively (P < 0.05). The conjunctival hyperemia appeared to increase back to baseline at later time points. No significant difference in the mean severity score among the groups was observed. True recurrence was found in 62 patients with no statistically significant difference among the groups. No serious ocular or systemic adverse events were seen. CONCLUSIONS: A single subconjunctival bevacizumab injection seems to only partially and transiently decrease conjunctival vascularization in impending recurrent pterygium in a dose-dependent manner. This treatment does not cause regression or reduce the recurrent rate of impending recurrent pterygium. PMID- 22081151 TI - Ocular surface reconstruction after exposure to high concentrations of antiseptic solutions. AB - PURPOSE: To report the clinical course in accidental exposure of the cornea to antiseptic solutions in 3 cases. METHODS: Observational case series. Exposure to 20% chlorhexidine gluconate solution was observed in 2 cases and to 10% benzalkonium chloride solution in 1 case. RESULTS: Not only superficial damage but also toxicity to corneal endothelial cells leading to corneal edema was observed in all 3 cases. Epithelial transplantation was performed: autologous cultivated limbal epithelial transplantation (auto-CLET), conjunctivolimbal autograft (CLAU), or living-related cultivated limbal epithelial transplantation (lr-CLET). A stable ocular surface was achieved, although exposure to high concentrations of antiseptic solutions caused severe anterior chamber inflammation; cataract and glaucoma developed in 2 cases, requiring further surgical treatment. CONCLUSIONS: Exposure to high concentrations of antiseptics causes both ocular surface and intraocular damage. Epithelial transplantation enables restoration of a stable ocular surface. However, management of intraocular consequences, including secondary glaucoma and corneal endothelial damage, still remains a challenge in the prognosis of such cases. PMID- 22081152 TI - Corneal cross-linking in patients with radial keratotomy: short-term follow-up. AB - PURPOSE: To record visual and refractive data in eyes with previous radial keratotomy (RK) and corneal instability undergoing corneal cross-linking (CXL). METHODS: Case series of eyes with RK and refractive instability undergoing CXL with riboflavin and UV-A radiation. The following variables were recorded before 3 and 6 months after CXL: sphere, spherical equivalent (SE), uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), topographic astigmatism, mean topographic K (Km), pachymetry, and Q values. RESULTS: Seven eyes of 4 patients with pre-CXL variables included mean sphere [-0.7 +/- 3.2 diopters (D)], astigmatism (2.5 +/- 1.17 D), SE (-2.1 +/- 3.1 D), UCVA (0.3 +/- 2.0), BSCVA (0.63 +/- 0.36), Km (38.75 +/- 5.74 D), pachymetry (522 +/- 36.8 MUm), and Q (1.73 +/- 1.34). Three months after CXL, mean sphere was +1.0 +/- 3.0 D (P = 0.00); astigmatism, 2.5 +/- 1.2 D (P = 0.95); SE, 0.3 +/- 2.2 D (P = 0.008); UCVA, 0.41 +/- 2.7 (P = 0.22); BSCVA, 0.80 +/- 0.27 (P = 0.14); Km, 37.5 +/- 5.7 D (P = 0.3); pachymetry, 491 +/- 33.74 MUm (P = 0.00); and Q, 2.27 +/- 1.8 (P = 0.22). Six months after CXL, mean sphere was 0.53 +/- 3.5 D (P = 0.00); astigmatism, 1.62 +/- 1.76 D (P = 0.13); SE, 0.52 +/- 2.9 D (P = 0.023); UCVA, 0.60 +/- 2.0 (P = 0.018); BSCVA, 0.9 +/- 0.15 (P = 0.03); Km, 38.3 +/- 4.10 D (P = 0.64); and Q, 1.7 +/- 0.78 (P = 0.80). CONCLUSIONS: Short-term follow-up of RK patients treated with CXL showed clinical and statistically significant improvement. PMID- 22081153 TI - Myopic LASIK in psychiatric patients. AB - PURPOSE: To evaluate the surgical results obtained in patients with psychiatric disorders who underwent myopic laser in situ keratomileusis. (LASIK). METHODS: Retrospective study of 156 eyes of 82 patients who underwent LASIK to correct a myopic spherical equivalent (SE) at Clinica Baviera-Instituto Oftalmologico Europeo, Bilbao, Spain. All procedures were performed with the Technolas Keracor 217 Z excimer laser. Patients had a preoperative diagnosis of bipolar disorder (79 eyes of 42 patients), schizophrenia (61 eyes of 32 patients), or obsessive compulsive disorder (16 eyes of 8 patients). Before surgery, the average sphere of the series was -3.92 +/- 2.24 D in the first group, -3.45 +/- 2.03 D in the second group, and -3.39 +/- 1.97 D in the third group. We surveyed the patients to analyze subjective assessment from the patient's perspective. RESULTS: At the last available visit after treatment, we obtained an SE of +/-0.50 D in 85.71% of eyes with bipolar disorder, 88.52% of eyes with schizophrenia, and 93.75% of eyes with obsessive-compulsive disorder. The efficacy index was 1.00 +/- 0.20 in the first group, 1.03 +/- 0.21 in the second group, and 1.00 +/- 0.07 in the third group. No eye lost 2 lines or more of best spectacle-corrected visual acuity. CONCLUSIONS: We found that patients with compensated psychiatric disorders, of which the surgeon was aware, achieved excellent results after surgery, with no remarkable complications. Patients tolerated the procedures well and were satisfied. PMID- 22081154 TI - Clinical and histopathological outcomes of subconjunctival triamcinolone injection for the treatment of acute ocular alkali burn in rabbits. AB - PURPOSE: To evaluate the efficacy and safety of subconjunctival injection of triamcinolone in the treatment of acute ocular alkali burn in rabbits. METHODS: Two groups of 5 rabbits were subjected to alkali burn (1 N NaOH). One group was treated with 1 subconjunctival injection of 0.3 mL of triamcinolone and the other with 1 subconjunctival injection of 0.3 mL of 0.9% saline. The affected corneas were observed for vascularization and opacity approximately 10 minutes after the burn and also after 7, 14, and 21 days. Photographs were taken for observation and statistical analyses. At all time intervals, the corneas were classified according to predetermined scores. Twenty-one days after the treatment, the animals were anesthetized, and their eyes were enucleated and processed for histopathology. RESULTS: Greater vascularization and opacity appeared in the animals that were treated with saline than in those treated with subconjunctival triamcinolone (vascularization: 7 days, P = 0.0107; 14 days, P = 0.0099; and 21 days, P = 0.0088; opacity: 7 days, P = 0.0079; 14 days, P = 0.0112; and 21 days, P = 0.0255). These results were also compatible with the morphological and statistical analyses, which revealed a more intense inflammatory process in the group treated with saline (P = 0.0317). No complications, such as corneal melting, perforation, or infection, were observed. CONCLUSIONS: Subconjunctival injection of triamcinolone may be a therapeutic option for the treatment of acute ocular burn because it reduced the corneal inflammatory process, opacity, and vascularization, with no apparent clinical changes in the general state of the animal. PMID- 22081155 TI - Treatment of fungal keratitis from Fusarium infection by corneal cross-linking. AB - PURPOSE: To evaluate the efficacy of corneal cross-linking (CXL) (riboflavin-UV A) as a simple therapy in Fusarium keratitis. METHODS: Twenty-four rabbits were systemically anesthetized, and the stromata of their right corneas were inoculated with Fusarium solani [10(5) colony-forming units (CFU) per milliliter]. Rabbits were divided into 2 groups: one was treated with CXL 72 hours after infection and the other did not receive any treatment (control). All eyes in both the groups were examined before (days 0 and 3) and after (day 7) CXL treatment. The eyes were enucleated, and corneal buttons were sent for microbiological and histological examinations. RESULTS: All animals developed Fusarium keratitis; there was no statistically significant difference between groups before treatment (day 0, P = 0.397 and day 3, P = 0.702). After CXL treatment, the difference in clinical scores on day 7 between groups was statistically significant (P = 0.00); the CXL group showed significant lower clinical score. The CXL group had 22.45 +/- 5.09 CFU/g compared with 42.5 +/- 3.12 CFU/g in the control group; this difference was statistically significant (P = 0.01). In the 3 buttons of the control group, similar amounts of Fusarium hyphae and inflammatory cells were observed. In 2 of the 3 buttons analyzed from the CXL group, fewer Fusarium hyphae, inflammatory cells, and nonspecific stromal changes were observed compared with the control group. CONCLUSIONS: Treatment of fungal keratitis with CXL seems to be effective in decreasing the intensity and severity of infectious keratitis by F. solani. This therapy may be useful as a coadjuvant in the medical treatment of resistant infections. PMID- 22081156 TI - Cytokinesis remnants define first neuronal asymmetry in vivo. AB - Polarization of a neuron begins with the appearance of the first neurite, thus defining the ultimate growth axis. Unlike late occurring polarity events (such as axonal growth), very little is known about this fundamental process. We show here that, in Drosophila melanogaster neurons in vivo, the first membrane deformation occurred 3.6 min after precursor division. Clustering of adhesion complex components (Bazooka (Par-3), cadherin-catenin) marked this place by 2.8 min after division; the upstream phosphatidylinositol 4,5-bisphosphate, by 0.7 min after division; and the furrow components RhoA and Aurora kinase, from the time of cytokinesis. Local DE-cadherin inactivation prevented sprout formation, whereas perturbation of division orientation did not alter polarization from the cytokinesis pole. This is, to our knowledge, the first molecular study of initial neuronal polarization in vivo. The mechanisms of polarization seem to be defined at the precursor stage. PMID- 22081157 TI - Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo. AB - Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices. PMID- 22081159 TI - Experience-dependent plasticity of mature adult-born neurons. AB - The adult olfactory bulb and hippocampus are continuously supplied with newborn neurons that are thought to possess a capacity for plasticity only at a young neuronal age, mainly during the early stages of integration into the network. We find that the two main types of adult-born neurons in the mouse olfactory bulb undergo experience-dependent plasticity long after maturation and integration, as evidenced by stabilization of synaptic turnover rates. Thus, the potential time window for plasticity of adult-born neurons extends well into maturity. PMID- 22081158 TI - Leptin regulates the reward value of nutrient. AB - We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake. PMID- 22081160 TI - Inactivity-induced increase in nAChRs upregulates Shal K(+) channels to stabilize synaptic potentials. AB - Long-term synaptic changes, which are essential for learning and memory, are dependent on homeostatic mechanisms that stabilize neural activity. Homeostatic responses have also been implicated in pathological conditions, including nicotine addiction. Although multiple homeostatic pathways have been described, little is known about how compensatory responses are tuned to prevent them from overshooting their optimal range of activity. We found that prolonged inhibition of nicotinic acetylcholine receptors (nAChRs), the major excitatory receptors in the Drosophila CNS, resulted in a homeostatic increase in the Drosophila alpha7 (Dalpha7)-nAChR. This response then induced an increase in the transient A-type K(+) current carried by Shaker cognate L (Shal; also known as voltage-gated K(+) channel 4, Kv4) channels. Although increasing Dalpha7-nAChRs boosted miniature excitatory postsynaptic currents, the ensuing increase in Shal channels served to stabilize postsynaptic potentials. These data identify a previously unknown mechanism for fine tuning the homeostatic response. PMID- 22081161 TI - Nictation, a dispersal behavior of the nematode Caenorhabditis elegans, is regulated by IL2 neurons. AB - Many nematodes show a stage-specific behavior called nictation in which a worm stands on its tail and waves its head in three dimensions. Here we show that nictation is a dispersal behavior regulated by a specific set of neurons, the IL2 cells, in C. elegans. We established assays for nictation and showed that cholinergic transmission was required for nictation. Cell type-specific rescue experiments and genetic ablation experiments revealed that the IL2 ciliated head neurons were essential for nictation. Intact cilia in IL2 neurons, but not in other ciliated head neurons, were essential, as the restoration of the corresponding wild-type gene activity in IL2 neurons alone in cilia-defective mutants was sufficient to restore nictation. Optogenetic activation of IL2 neurons induced nictation, suggesting that signals from IL2 neurons are sufficient for nictation. Finally, we demonstrated that nictation is required for transmission of C. elegans to a new niche using flies as artificial carriers, suggesting a role of nictation as a dispersal and survival strategy under harsh conditions. PMID- 22081162 TI - Sympathetic magic and gambling: adherence to the law of contagion varies with gambling severity. AB - This study assessed adherence to the law of contagion by 118 undergraduate students (39 males). Participants were students who played a slot machine game after viewing a prior player who seemed to be winning ("lucky" condition) or losing ("unlucky" condition). Adherence to the law of contagion was assessed by the selection of the coin holder used by a "lucky" prior player and the avoidance of the coin holder used by an "unlucky" prior player. Contagion varied directly with scores on the Problem Gambling Severity Index and scores on the Luck/Perseverance subscale of the Gamblers' Belief Questionnaire (Steenbergh et al. in Psychol Addict Behav 16(2):143-149, 2002). Gamblers high in problem severity chose the "lucky" coin holder and avoided the "unlucky" coin holder significantly more than gamblers low in problem severity. Problem gamblers, therefore, exhibit evidence of magical thinking related to the transfer of a "lucky" essence. The same was the case for individuals with a strong level of belief that sheer continuation in gambling (luck perseverance) results in success and for individuals who believe that luck is a personal rather than a situational characteristic. All three variables (problem gambling severity, luck perseverance and personal luck) had direct effects on behavior reflecting irrational magical thinking. A belief that knowledge or skill has a role in successful gaming was unrelated to magical thinking. These findings suggest potential foci for cognitive interventions with problem gamblers and those with non-skill based evidence of irrational thinking. PMID- 22081163 TI - Is there still a need for strengthening optometrist referral and general public awareness regarding cataract even in developed countries? PMID- 22081164 TI - Nephrotic-range proteinuria in a child with retinoic acid syndrome. AB - BACKGROUND: All-trans retinoic acid (ATRA) is a vitamin A derivative that is used in combination with chemotherapy to treat acute promyelocytic leukemia (APL). A serious complication of ATRA is retinoic acid syndrome (RAS), which is characterized by an inflammatory reaction with capillary leakage and myeloid cell tissue invasion that presents with cardiopulmonary symptoms and occasionally acute kidney injury. CASE-DIAGNOSIS/TREATMENT: We report the case of a 3-year-old child with APL who developed transient nephrotic-range proteinuria (max urine protein:creatinine ratio 8.6) during two episodes of RAS while on ATRA therapy. ATRA was temporarily discontinued and the patient was treated with a 3-day course of dexamethasone during each episode. He maintained normal renal function throughout and the proteinuria completely resolved. CONCLUSIONS: This is the first reported occurrence of nephrotic-range proteinuria in a child treated with ATRA. Nephrologists should be aware that RAS is a serious complication of ATRA that may lead to proteinuria. PMID- 22081166 TI - The effect of family size on spanish simple and complex words. AB - This study presents the results of three experiments in which the Family Size (FS) effect is explored. The first experiment is carried out with no prime on simple words. The second and third experiments are carried out with morphological priming on complex words. In the first experiment a facilitatory effect of FS is observed: high FS targets produced faster responses than low FS targets. However, an inhibitory effect of Stem-FS is observed in the second experiment: low Stem-FS targets produced faster responses than high Stem-FS targets. In the third experiment a facilitatory effect is observed when the Affix-FS is manipulated: high Affix-FS targets produced faster responses than low Affix-FS targets. Overall data confirms that the effect of FS plays an important role in lexical access in Spanish. The results also show that the effect of FS is modulated by the lexical nature of the prime (lexical or sublexical) and by the number of candidates activated. Finally, it is suggested that the nonwords employed were decisive in obtaining the results mentioned. PMID- 22081165 TI - Treatment of children with Henoch-Schonlein purpura nephritis with mycophenolate mofetil. AB - BACKGROUND: Henoch-Schonlein purpura (HSP) can progress to Henoch-Schonlein purpura nephritis (HSPN), and the most effective management remains unclear. Our aim was to evaluate the efficacy of mycophenolate mofetil (MMF) for treating pediatric patients with HSPN and nephrotic-range proteinuria. METHODS: Twelve children, seven boys and five girls, mean age 8.33 (range 6-12) years at the time of HSPN diagnosis with nephrotic-range proteinuria, were treated with MMF. All patients failed steroid treatment, and mean proteinuria at the time of MMF initiation was 5.6 g/d. MMF dosage ranged from 20 to 25 mg/kg per day. Patients also received an angiotensin-converting enzyme inhibitor (cliazapril) at MMF initiation. Mean follow-up was 3.9 (range 2.3-5.5) years. RESULTS: All patients responded to MMF at a mean of 2.5 (range 1-4 months). Among the 12 patients, MMF was administered for 10 months in five, 12 months in six, and 15 months in one. At last follow-up, all patients had negative proteinuria and normal renal function, and no relapses were noted. No serious adverse effects of MMF were noted in any patient. CONCLUSION: MMF is useful for treating pediatric patients with HSPN and nephrotic-range proteinuria. PMID- 22081167 TI - Interactions among Glomus irregulare, arbuscular mycorrhizal spore-associated bacteria, and plant pathogens under in vitro conditions. AB - Arbuscular mycorrhizal (AM) fungi interact with bacteria (AM fungi-associated bacteria, AMB) in the mycorrhizosphere. We previously identified a set of AMB that enhance AM fungal colonization, plant growth, and inhibit pathogens. Here, we used transformed carrot root cultures in a two-compartment plate system for further in vitro studies on interactions taking place among Glomus irregulare (syn.Glomus intraradices), AMB, and plant pathogens. We found that exudates of G. irregulare stimulated growth of all ten AMB isolates tested in multi-well plates. AMB growth stimulation was observed also during co-cultivation of three of these AMB with G. irregulare in the hyphal compartment. In addition, co-cultivation stimulated growth of G. irregulare hyphae and spore production, as well as G. irregulare root colonization. GC/MS analysis in a preliminary screening of metabolites revealed differences in concentrations of several identified but also unidentified compounds in G. irregulare hyphal exudates. Exudates in presence of three different AMB isolates co-cultivated with G. irregulare contained several additional compounds that differed in amount compared with G. irregulare alone. The results indicate that G. irregulare exudates contain carbohydrates, amino acids, and unidentified compounds that could serve as a substrate to stimulate AMB growth. With regard to effects on plant pathogens, growth inhibition of Rhizoctonia solani, Verticillium dahliae, and Pectobacterium carotovorum ssp. carotovorum was evident in the presence of the AMB isolates tested together with the G. irregulare exudates. These in vitro studies suggest that G. irregulare and AMB stimulate growth of each other and that they together seem to provide an additive effect against growth of both fungal and bacterial pathogens. PMID- 22081169 TI - Prenatal nutrition among rural Bangladeshi pregnant women. AB - The expected outcome of pregnancy is a healthy mother with a healthy child. The single most important care which could prevent the negative outcomes of pregnancy is Antenatal Care (ANC). Proper and timely antenatal care can significantly reduce the risks of maternal mortality. In pregnancy, total cost is about 80,000 Kcal, and above normal energy requirements. To find out prenatal nutrition an exploratory study was carried out in seven villages of the Ward-2 of Jamtoil Union of Kamarkhand Upazila under Sirajganj District. Thirty pregnant women of different trimesters, gravida and parity had been studied employing the methods and techniques of "Ethnographic Field Work." Mean daily calorie consumption of the Key Informants (KIs) was 1480.49 Kcal without reference to their religious affiliation, family resource base, education, occupation, gravidity, parity and duration of pregnancy. This is indicated that the mean calorie intake of the Key Informants did not meet not only their prenatal nutritional need but also their requirement during pre-pregnancy period. It was observed that food intake was in no way different from that of the non-pregnant status. Antenatal care of rural inhabitants analyzed almost exclusively from biomedical perspectives, its cultural, socio-economic, gender, ecological and other relevant perspectives are mostly ignored. In order to have safe motherhood up through compliance of prenatal advice, nutritional one in particular, these factors should be taken into consideration. PMID- 22081168 TI - Paralemniscal TIP39 is induced in rat dams and may participate in maternal functions. AB - The paralemniscal area, situated between the pontine reticular formation and the lateral lemniscus in the pontomesencephalic tegmentum contains some tuberoinfundibular peptide of 39 residues (TIP39)-expressing neurons. In the present study, we measured a 4 times increase in the level of TIP39 mRNA in the paralemniscal area of lactating mothers as opposed to nulliparous females and mothers deprived of pups using real-time RT-PCR. In situ hybridization histochemistry and immunolabeling demonstrated that the induction of TIP39 in mothers takes place within the medial paralemniscal nucleus, a cytoarchitectonically distinct part of the paralemniscal area, and that the increase in TIP39 mRNA levels translates into elevated peptide levels in dams. The paralemniscal area has been implicated in maternal control as well as in pain perception. To establish the function of induced TIP39, we investigated the activation of TIP39 neurons in response to pup exposure as maternal, and formalin injection as noxious stimulus. Both stimuli elicited c-fos expression in the paralemniscal area. Subsequent double labeling demonstrated that 95% of neurons expressing Fos in response to pup exposure also contained TIP39 immunoreactivity and 91% of TIP39 neurons showed c-fos activation by pup exposure. In contrast, formalin-induced Fos does not co-localize with TIP39. Instead, most formalin activated neurons are situated medial to the TIP39 cell group. Our data indicate that paralemniscal neurons may be involved in the processing of maternal and nociceptive information. However, two different groups of paralemniscal neurons participate in the two functions. In particular, TIP39 neurons may participate in the control of maternal functions. PMID- 22081170 TI - Feeding practices and nutritional status of children under two years of age. AB - A descriptive cross sectional study was done in the department of Pediatrics Mymensingh Medical College Hospital. The purpose of the study was to assess breast feeding pattern, complementary feeding pattern, types of complementary foods and also to assess the nutritional status and to detect any relationship with the nutritional status and the feeding practices. Mothers with their children aged less than 2 years were included and very sick children, mother less children, handicapped children were excluded. Four hundred (400) consecutive children were enrolled from eight upazillas of Mymensingh district who were selected randomly. Out of 400 children, 214 children (53.5%) were male and 186 children (47.5%) were female and M:F was 1.2:1. Exclusive breastfeeding rate was 41.5%. Pre-lacteal feeding rate were 30.7% and most common pre-lacteal foods were honey and sugar water. Colostrum was given in 69.3% children. Breast feeding continued at the time of interview was 58.1%. Complementary feeding started in time in 35.8%, early weaning in 44.5% children. Type of complementary food was mainly luta (rice powder mixed with boiled water and sugar only) in 38.8% and khichuri (rice, pulses, soybean oil) in 19.5%. Bottle feeding rate was 31.30%. Around 43% children were underweight and 10.25% children were severely underweight and common in between 12 to 23 months of age group. Around 29% children were stunted among 11.25% were severely stunted. About 13.5% children were wasted and among them 2.5% were severely wasted. Stunting prevalent over the age of 9 months and wasting started after 6 months of age. Malnutrition was common in partially breast fed and early weaning with carbohydrate rich food. PMID- 22081171 TI - Intra-vaginal use of misoprostol for induction of labour in intrauterine death. AB - This prospective study was done in the Department of Obstetric & Gynaecology in Mymensingh Medical College & Hospital during the period of February 2006 to January 2007, to assess the efficacy of vaginal misoprostol for induction of labour in intrauterine foetal death cases and to detect any intrapartum or postpartum complications. For this study, 50 cases of IUD were selected among admitted patients who were diagnosed by detailed history, clinical examination and by USG. Fifty microgram of misoprostol was given per vaginally, which was repeated 4 hours interval upto effective uterine contraction to a maximum six doses. All the informations were recorded in a predesigned structured data collection sheet and data had been interpreted through appropriate statistical analysis. In this study, 46% patients were within 18-25 years of age and gestational age between 28-37 weeks was 80%. Regarding causes of IUD, commonest was idiopathic (52%), next was gestational hypertension, pre-eclampsia, impending eclampsia (28%). Most of the patients (80%) had no history of antenatal checkup and belongs to below average socioeconomic status. Most case (64%) had less Bishop's score (<3) & all cases had unfavourable cervix, score <6. Vaginal delivery was 98% and 2% needed caesarean section. Mean induction delivery interval was 11.8 hours. Induction delivery interval was within 6-23 hours and 66% cases needed 2-3 doses of vaginal misoprostol. Complications were found in a minor group of patients. Nausea, vomiting, occurred in 12% of cases. Others were fever (2%), shivering (6%), PPH (4%), chorioamniotitis (2%) etc. Vaginal misoprostol for cervical ripening and labour induction is very effective and shorten the time of induction delivery interval. On the other hand, misoprostol is quite cheap, easy to administer, well tolerability and less side effects. PMID- 22081172 TI - Correlation between clinical presentation, peroperative finding and histopathological report in acute appendicitis. AB - Acute appendicitis is usually encountered clinically as acute abdomen. Typical cases are easy to diagnose, but sometimes it is very difficult to make a diagnosis in atypical cases. The objective of the study was to determine the diagnostic accuracy in patient of clinically diagnosed acute appendicitis. This prospective study conducted in Mymensingh medical college hospital on 1136 patients presented with acute abdomen and clinically diagnosed as acute appendicitis from July 2004 to June 2010. Emergency appendicectomy was done in all consecutive patients after relevant investigation. Intraoperative findings along with histopathological reports were compared with clinical diagnosis. On the basis of histopathological report, 85.65% were found to have acute appendicitis with misdiagnosis in rest of the subjects requiring unnecessary explorations. Negative exploration was more in emergency than office hour. This may be due to diagnostic inaccuracy and decision-making in the management of the acute appendicitis. Management errors can be significantly reduced by accurate preoperative diagnosis of acute appendicitis by improving clinical skill and appropriate investigations. PMID- 22081173 TI - Superiority of measuring apolipoprotein B to conventional lipid profile predicting risk of acute coronary syndrome in young people. AB - The purpose of this study is to compare the importance and its superiority of apolipoprotein B (apoB) over conventional lipid profile for predicting risk of acute coronary syndrome in young people of Bangladesh. This case-control study was carried out in Department of Cardiology, of Mymensingh Medical College Hospital within the period from June 2009 to May 2010. A total 50 case of 18-45 years of age with first attack of acute coronary syndrome admitted in coronary care unit and 50 healthy controls of same age and sex distribution were studied. Twenty five (50.0%) of the studied case had hyper apoB condition, those low density lipoprotein cholesterol (LDL-C) level was normal, thus conventional lipid profile underestimated the risk. Among the controls 23(46.0%) with high LDL-C had hyper apoB condition. Hyper-ApoB in these controls may cause acute coronary syndrome in future. The present study shows significant association of apolipoprotein B as an independent determinant and estimation of apoB other than conventional lipid profile may be an alternative tool for predicting risk of development of acute coronary syndrome in young people. PMID- 22081174 TI - Postoperative pain relief following inguinal hernia repair in children by wound infiltration with levobupivacaine. AB - The present study has been designed to compare the postoperative pain relief for inguinal hernia repair in children through wound infiltration with levobupivacaine with that provided by paracetamol administration per rectaly. This interventional study was carried out in the Department of Paediatric surgery, Mymensingh Medical College Hospital, Mymensingh and Dhaka Medical College Hospital, Dhaka, during the period from January 2009 to September 2010. A total of 120 patients were included in this study. Among them 60 patients in Group-A (study group) where post incisional wound infiltration with levobupivacain after inguinal herniotomy and before skin closure was done and 60 patients in Group-B (control group) where paracetamol was given per rectally after anesthesia induction. Both groups were followed up post operatively for 23 hours. In Group A maximum analgesic period was 8.30 hours and minimum analgesic period was 5.30 hours. On the other hand in Group B maximum analgesic period was 6.50 hours and minimum analgesic period was 4.50 hours. Duration of post operative analgesia between two groups of the patients were significant [p<0.01]. Post incisional wound infiltration with levobupivacain has significantly better efficacy to rectal administration of paracetamol with respect to providing pain relief following inguinal hernia repair in children. Longer duration of analgesic action is more achieved in the Levobupivacaine group. PMID- 22081175 TI - Nonspirometric aspects of pulmonary function in subjects with dust industries. AB - Bangladesh is a developing country. Many workers are involved in different industries which are polluted with dust e.g. saw mill, rice mill, jarda factory etc. The present study may give a preliminary idea about the lung function status of those workers. The study has been designed to analyze the lung function status of those workers by measuring TCO2 aiming to recommend necessary steps to improved the quality of life of workers of dust industry in our socioeconomic context. This study was to evaluate pulmonary functional status of those workers who are exposed to dust in industries like saw mill 26.00 mmol/l, rice mill 31.10 mmol/l and jarda factory 22.11 mmol/l. In all groups p values were >0.1 which was not significant except jarda factory worker in which p value was <0.001 and it was highly significant. This study was carried out to increase the awareness of the workers and to reduce the cost of employment. PMID- 22081176 TI - Different doses of atropine on heart rate fluctuations during reversal of neuromuscular blockade. AB - It was a prospective comparative clinical study carried out in the Department of Anaesthesia, Combined Military Hospital (CMH), Dhaka, to evaluate the heart rate changes during reversal of neuromuscular blockade by using 3 different doses of atropine (in a mixture with neostigmine) and thereby detect comparatively safer dose. Sixty patients of ASA (American Society of Anesthesiologists) grade I and II physical status were divided equally into 3 groups. Neostigmine 0.05 mg/kg body weight mixed with atropine 0.02, 0.015 and 0.01 mg/kg body weight given intravenously in group A, B and C respectively during reversal. The 3 groups were compared in age, sex, body weight, and ASA grades, but there was no significant difference (p>0.05) between 3 groups. It is revealed that in Group C (atropine at a dose of 0.01 mg/kg with neostigmine), heart rate affected very little but salivary and tracheobronchial secretions were more. One of them had laryngospasm which was managed conservatively. In Group B (who received atropine 0.015 mg/kg) incidence of tachycardia observed was less than Group A (who received atropine 0.02 mg/kg). The patients of this group also had some salivary secretions but less than group C. Tachycardia was most marked in Group A but had minimum salivary secretions. Statistical analysis of heart rate changes in different times among the 3 Groups was significant (p<0.05). It was highly significant (p<0.01) in 1 minute after reversal. So relatively lower dose (0.015 mg/kg) of atropine with neostigmine than the conventional dose (0.02mg/kg) can be used to decrease tachycardia during reversal of neuromuscular blockade especially in haemodynamically unstable patients. PMID- 22081177 TI - Role of ETT to diagnose coronary artery disease. AB - The purpose of the study to predict the coronary arterial disease by exercise treadmill scoring system and to see the correlation of angiographic extent of coronary artery disease by high treadmill score in our country. The present prospective study carried out in the department of cardiology, Bangabandhu Sheikh Mujib Medical University, University Cardiac Centre during the period of January 2006 to July 2006. Based on inclusion and exclusion criteria a total of 80 patient of chronic stable angina or chest pain evaluation having positive ETT who were admitted in university cardiac centre in Bangabandhu Sheikh Mujib Medical University and underwent coronary angiogram within one month were the study population. Among 80 subjects 60(75%) were male and 20(25%) were female and male: female ratio 3:1 Mean age of male subject 51.37+/-9.08 years and mean age of female subjects were 43.75+/-7.67 years. Three quarter of the subject had the history of typical anginal pain followed by 21.3% atypical and 3.8% pain of non anginal origin. All the risk factors like, dyslipidemia (90%), HTN (68.8%) past smoker (45%), current smoker (32.5%), diabetes (36.3%), family history of coronary artery disease (25%) and sudden death of first degree relatives (8.8%); dyslipidemia was the highest percentage. Among 80 subjects more than one third 35% (28) of the subjects were observed to be normal by angiogram, 28.8% (23) had SVD, 16.3% (13) DVD and 20% (16) TVD. Approximately 70% of the significant stenosis was predicted as having high probability of 30.8% as intermediate probability and none as low probability with exercise test scores. Multi-vessel coronary artery disease were predicted by high probability exercise test score 82.8%. Thus high probability score needs urgent coronary angiogram. PMID- 22081178 TI - Comparative study between combination of famciclovir and prednisolone with prednisolone alone in acute Bell's palsy. AB - The antiviral drug acyclovir or its analogue, valacyclovir, has been applied in various trials on Bell's palsy with inconsistent results. We compared the therapeutic effect of famciclovir plus prednisolone with prednisolone alone, in patients with Bell's palsy. In a randomized, prospective trial, 68 patients were randomized to treatment with famciclovir and prednisolone (34 patients) or prednisolone alone (34 patients). All patients underwent supportive therapy. Severity of Bell's palsy was evaluated using the House-Brackmann scale (HBS). Follow-up was done after 1 week, 1 month and 3 months, with complete recovery defined as House-Brackmann grade I. The analysis revealed that recovery rates at month 1 and 3 were significantly higher in combination group than that of prednisolone only group (94.1% vs. 61.8% and 97.1% vs. 74.5% respectively). Again recovery from mild to moderate (HBS-II, III, IV) Bell's palsy occurred completely at month 3 and that of severe (HBS-V, VI) Bell's palsy was two-third of the patients. Again in severe Bell's palsy combination treatment increased the chance of complete recovery more than 10-fold than that of steroid only. The study results suggest that better outcome for Bell's palsy patients occurred if they were treated with prednisolone and famciclovir combination instead of prednisolone alone. In fact a considerable number of patients were benefited from additional antiviral therapy with famciclovir. PMID- 22081179 TI - Serum hyaluronic acid as a predictor of fibrosis in chronic hepatitis B and C virus infection. AB - Chronic hepatitis B and C virus infection can lead to cirrhosis and hepatocellular carcinoma. Several studies investigated the diagnostic and prognostic value of some biochemical markers to detect the hepatic fibrosis and found a correlation between serum markers and hepatic fibrosis. Among them serum hyaluronic acid (HA) has been identified as a potential marker of fibrosis or cirrhosis in different studies. A prospective study in 60 subjects was conducted to evaluate the association between serum HA and hepatic fibrosis. Thirty consecutive patients with chronic HBV or HCV infection undergoing liver biopsy were studied. Sera were obtained for HA using enzyme linked protein binding assay. Patients with hepatic fibrosis had higher serum HA concentration compared with healthy subjects (236.65 +/- 227.07 vs. 23.32 +/- 14.22 respectively, p<0.001). Correlation was found between high serum HA concentration and increasing degree of hepatic fibrosis (R-0.322 and p<0.041). This study had shown a good correlation between serum HA and different stages of hepatic fibrosis. So serum HA may be used as a useful marker of hepatic fibrosis. PMID- 22081180 TI - Outcome of pregnancy in patients with congenital heart diseases. AB - This prospective study was conducted to evaluate the outcome of pregnancies in women with congenital heart diseases. In this study 50 pregnant women age between 20-45 years with congenital heart diseases were included. Twenty two (44%) were presented with atrial septal defect, 12(24%) with ventricular septal defect, 5(10%) were with patent ductus arteriosus, 6(12%) with Fallot's tetralogy, 2(4%) with pulmonary stenosis, 2(4%) with Eisenmenger syndrome, 1(2%) with dextrocardia. Shortness of breath (60%) was the main presenting complaint. Normal vaginal delivery (52%) was done in majority of cases. Spontaneous abortion occurred in 16% of pregnancies. Major complications were heart failure 16%, arrhythmias 21%, cardiovascular mortality 4%, preeclampsia 4%, and eclampsia 2%. Premature birth 16%, fetal demise 4%, neonatal death 2% and cardiac anomaly at birth 2% were also observed. The outcome of pregnancy in women with congenital heart diseases is favourable with considerable maternal and neonatal complications. PMID- 22081181 TI - Management of differentiated thyroid carcinoma. AB - The study was done to determine the clinical, radiological and histopathological characteristics along with the management outcome of differentiated thyroid carcinoma. This Retrospective study included sixty patients with differentiated thyroid carcinoma presented to Department of Otolaryngology and Head-Neck Surgery at Dhaka Medical College Hospital and Apollo Hospitals Dhaka from June 2006 to December 2008. The data of each patient included age, sex, presenting symptoms and signs, provisional diagnosis, preoperative investigations, operation notes, histopathological examination and state at follow up. This study included 28 males and 32 females. The mean age was 42.7 years. Maximum patients presented at 4th decade. The commonest presentation was thyroid swelling followed by lateral neck swelling. Detailed clinical assessment before operative treatment has been done for all patients. Fifty five patients (91.66%) presented with single nodule. Distant metastasis was found in 2 cases. All patients underwent fine needle aspiration cytology which was conclusive in 38 patients (63.33%). All the sixty patients underwent surgical excision; either total thyroidectomy or completion thyroidectomy. Neck dissection was performed in 8 patients. All patients received postoperative radio-iodine. Fifty one cases were papillary carcinoma and 9 cases were follicular carcinoma. Except for one case with local recurrence the remaining cases were disease free on follow up (up to 10-40 months). One patient died with bone metastasis 2 years after operation. Of all thyroid cancers, majority cases are papillary cancer (85%). In contrast to other cancers, thyroid cancer is almost always curable. Most thyroid cancers grow slowly and are associated with a very favorable prognosis. Early diagnosis and treatment of the same is strongly advisable. PMID- 22081182 TI - Forgotten urological stent. AB - "Forgotten" Ureteral stent DJ stent related complication is not uncommon even in the era of modern urology in the developed world. In this context we have undertaken a retro-prospective study in relation to its various causes, complications, management and prevention of forgotten stents in a single teaching institute. The study period was from January'04 to December'09. The sample size was 60. The effect of "forgotten stent" in our study reflects mild UTI to various complications including severe renal failure. We had approached all of our cases judiciously using various modalities of minimal access endourological techniques either alone or in combinations with successful outcome. The study concluded that it is vary easy to prevent "forgotten stent" and so its complications. However if we confront such unwanted complications that could be managed successfully with the use of endourological techniques. We did not use other techniques like laparoscopy and open surgery in this study. PMID- 22081183 TI - Prevalence of stroke above forty years. AB - Number of elderly persons gradually increased in Bangladesh due to improved health awareness and health care. Age is the single most important risk factor for stroke. This study aims at finding the prevalence of stroke in a Bangladeshi population aged forty years and above. The cases of stroke were ascertained in two phases of door-to-door survey. In phase-I, trained interviewers performed face-to-face interview with subjects for the detection stroke cases using the World Health Organization (WHO) screening protocol for neurological diseases. In phase-II, subjects suspected to have a stroke underwent a clinical evaluation for diagnosis or exclusion of stroke by a neurological team. The study involved 15627 participants aged 40 years and above. A total of 47 participants found to have stroke, expressing an overall prevalence rate of 3.00 per 1000 (95% CI 0.95 to 2.45). Prevalence of stroke were 2.0, 3.0, 2.0, 10.0, and 10.0 per 1000 within age groups of 40-49 years, 50-59 years, 60-69 years, 70-79 years and 80 years and above age group respectively. Prevalence of stroke in people with age range 70-79 years compared to 40-49 years age range is 4.988 (95% CI 2.309 to 10.77) times and people with age range >=80 years compared to 40-49 years age range is 4.798 (95% CI 1.597 to14.416) times. Prevalence was higher among men in comparison with women. The male: female ratio is 3.44:2.41 per 1000 respectively. Bangladeshi male populations in rural areas are found to have stroke more than urban people. A large community based study should be undertaken to further confirm the result of this present study. PMID- 22081184 TI - Fluctuation of pain by weather change in musculoskeletal disorders. AB - In order to find out the fluctuation of pain by weather change, a descriptive cross-sectional study was conducted among 138 individuals having musculoskeletal disorders (MSDs) attending the out patient department (OPD) of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka, during March 2004 to June 2004. Data were collected by face to face interview employing a pre-tested interview schedule containing structured questions. Among 138 respondents, male were predominant (52.2%). Mean age of the respondents was 39.42+/-10.79 years, while the most common age group was found as '31 to 40 years'. By occupation, majority were housewives (40.58%), followed by businessmen (29.71%), service holder (15.22%), laborer (7.97%), and students (6.52%). The primary sites of pain were back and low back (38.4%), knee (24.6%), leg (8.7%), ankle and heel (8.0%), hand and wrist (6.5%), neck (5.8%), shoulder (5.8%), and elbow (2.2%). Highest number (47.8%) patients reported aching pain, while one fifth (20.3%) of them experienced burning pain. About 36.2 percent respondents mentioned 'prolonged standing' as the main cause of pain aggravation, while almost half (48.6%) of the patients perceived that 'application of heat' was the key relieving factor of their pain. About two third (63%) of the respondents were sensitive to weather change; among them 56.3 percent reported that their pain increased during cold weather. Moreover, more than two third (67.4%) study-patients experienced deterioration of pain due to seasonal variation; of them 59.1 percent reported that their pain was exacerbated in winter season. Of all respondents, less than one third (30.4%) experienced aggravation of pain due to lunar change; of them majority (85.7%) experienced increased pain during dark fortnights. Our study concluded that weather change might have an important role in fluctuation of pain among individuals having musculoskeletal disorders. PMID- 22081185 TI - Morphological pattern of glomerular diseases in adult nephrotic syndrome. AB - Nephrotic syndrome can result from a large number of glomerular lesions. The primary or idiopathic nephrotic syndrome is a condition which develops as a result of primary glomerular disorders of the kidney. From July 2005 to June 2007, renal biopsies were done in all patients of adult nephrotic syndrome. Renal biopsies were evaluated by light and immunofluorescence microscopy. Out of 74 renal biopsies primary nephrotic syndrome was 70. Male was 64.9% and; 35.1% was female patients. Average age was (33.14+/-11.70) years. The main morphological pattern was Mesangialproliferative glomerulonephritis 36.48% followed by membranoproliferative glomerulonephritis 20.27%. Membranous nephropathy (10.81%) was not much common in our country. PMID- 22081186 TI - Diagnosis of breast lump by fine needle aspiration cytology and mammography. AB - Breast carcinoma is the most common malignant tumour and the leading cause of death from cancer in women. A large number of patients in Bangladesh have been suffering from breast cancer. Now-a-days, Fine needle aspiration cytology (FNAC) is being performed as a pre-operative test to evaluate breast lump. FNAC is cost effective and can prevent unnecessary surgery. As FNAC became more reliable in diagnosing malignancy and thereby the use of frozen-section histology had been reduced by about 80%. But erroneous diagnosis is more common with FNAC than with histopathology. However, mammography can identify breast cancers too small to palpate on physical examination and theoretically beneficial to diagnose even noninvasive lesions. Present study aimed to see the accuracy of FNAC and mammography in the diagnosis of palpable breast lumps and to study their correlation. In this study 222 patients were included in the study and FNAC was done in all the patients. Mammography was done in 112 cases. Among these 112 patients 32 cases were found malignant. Histopathology was done in total 89 cases. Among 112 patients who were underwent mammography only 43 were found for histopathology. Finally, 36 cases were found malignant. Fibroadenoma is mostly found in below 20 years group and malignancy is mostly occurring in older age group. Mammography shows total 8 false positive and 5 false negative cases. FNAC shows only 1 false positive and 1 false negative case. On analysis mammography showed 82.76% sensitivity, 90.36% specificity, 75% Positive predictive value (PPV), 93.75% Negative predictive value (NPV) and 88.39% accuracy. FNAC showed 97.22% sensitivity, 99.46% specificity, 97.220% PPV, 99.46% NPV and 99.095% accuracy. Mammography was found to be less sensitive, specific and accurate in the diagnosis of breast lump though there is highly significant correlation among them. However, the study has shown a much higher performance of FNAC than other previous studies indicating the improved skill in cytological diagnosis to a satisfactory level. PMID- 22081187 TI - Physical training induced resting bradycardia and its association with cardiac autonomic nervous activities. AB - Regular physical exercise causes resting bradycardia. This exercise-induced resting bradycardia may be associated with exercise-induced changes in Cardiac autonomic nervous activities (CANA). Power Spectral Analysis (PSA) of Heart rate variability (HRV) is one of the most promising new techniques to quantify CANA. Regular physical exercise induced bradycardia is associated with exercise-induced adaptation in CANA. To observe the HRV parameters by frequency domain method (PSA), in male adolescent athletes in order to find out the influence of regular physical exercise on resting heart rate (HR) and CANA. The cross sectional study was carried out on 62 adolescent male athletes aged 12-18 years (group B), in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University from 1st July 2007 to 30th June 2008. For comparison 30 age, sex and socioeconomic condition matched apparently healthy sedentary subjects (group A) were also studied. The study group was selected from the BKSP (Bangladesh Krira Shikka Prothistan, Savar, Dhaka) and the control from a residential school of Dhaka city. HRV parameters were assessed by Polygraph (Polyrite D, version 2.2). For statistical analysis Independent-Samples t-test was done as applicable. Resting mean HR was significantly (p<0.001) lower in the athletes. The mean value of Total (variance), VLF, LF and HF power was significantly (p<0.001) higher in athletes than that of non-athetes. Regular physical exercise-induced resting bradycardia is associated with exercise-induced adaptation in cardiac autonomic nervous activities. PMID- 22081188 TI - Parental knowledge, attitude and practice related to blindness of children in some selected Upazilla of Bangladesh. AB - Early detection of blind children at the household and community level is critical in reducing the global burden of visual impairment and childhood blindness. The aim of the study is to identify a range of potential issues relating to parental awareness and perceptions of common eye diseases affecting children. It was a descriptive and cross sectional study. Parents were recruited from four selected Upazillas ('pouroshoba' - 25% and rural - 75%) in the Naogaon district of Bangladesh. The method used in this study to assess parental knowledge and belief was by means of a questionnaire. The selected subjects were interviewed in detail using a structured questionnaire. It is mentionable that among common eye disease, about three-fourth of the parents informed that vitamin A deficiency was the leading cause of blindness and more than one quarter believed that eye infection was the important cause of childhood blindness. Very few reported that injury in eye was the cause of childhood blindness. Analysis of respondents of this study revealed that half of the parents believed that childhood cataract is untreatable. Approximately 90% those surveyed were unaware of schooling systems for blind children and only 5% sought treatment from an ophthalmologist. This study also demonstrates that the health seeking behavior of parents and their extended families is poor. The mean age of the parents was 32.5+/-9.3 years, about 75% of parents had education up to primary level, and only 3.7% of them had graduation degree and above. The findings reinforce the necessity of parental awareness of common eye diseases in children and the importance of seeking timely advice including treatment based on informed decisions. PMID- 22081189 TI - Ondansetron versus granisetron in the prevention of chemotherapy induced nausea and vomiting in children with acute lymphoblastic leukemia. AB - Effect of ondansetron and granisetron were evaluated in sixty (60) children (age 4-11 years) irrespective of sex, diagnosed case of acute lymphoblastic leukemia (ALL) who received high dose methotrexate and did not receive any antiemetic 24 hours prior to HDMTX. This was a prospective, randomized, double-blind, single center study. Of 60 children, 30 received oral ondansetron (4mg) and rest 30 granisetron (1mg) half an hour before therapy. Drugs were randomly allocated with appropriate code. The patients were followed up from day 1 to day 5 of therapy. Episodes of nausea and vomiting were recorded and scorings was done every 24 hours following chemotherapy. No significant difference was found between two groups according to acute emesis (Day-1) (p=0.053). In day two and day three it was significant (p<0.05). In day four it was significant (p=0.002). Early chemotherapy induced nausea and vomiting (CINV) were controlled 90% in children who received granisetron and 70% in children who received ondansetron. Delayed (Day 2-4) CINV were controlled in 80% of children who received granisetron and 43.4% who received ondansetron (p<0.05). Granisetron group required additional doses only 3.3% cases and ondanseton group 30% cases on the second day (p<0.05). Result was significant between two groups. About 36.7% patients had episodes of nausea on day four of chemotherapy in ondansetron group and it was only 3.3% in granisetron group due to adverse effects of antiemetic drug itself (p=0.001). Maximum episodes of vomiting were found on the second day in ondansetron group 33.3% and in granisetron group 3.3% (p=0.003). Though adverse effects like headache, constipation, abdominal pain and loose motion were common in both group of children but their number was much less in children who received granisetron. On second day of therapy score of nausea and vomiting was maximum in ondansetron and minimum in granisetron treated on day 4 and the result was significant. So, to prevent acute and delayed CINV in children with ALL, oral graniseteron can be considered as more effective and well tolerated with minimum adverse effects compared with ondansetrons. PMID- 22081190 TI - Effect of low dose levodopa on motor outcome of different types of stroke. AB - This case control study interventional study was carried out in Neurology out patient department of Bangabandhu Sheikh Mujib Medical University (BSMMU) from January 2004 to June 2005. The aim of the study was to investigate the effect of low dose levodopa on motor outcome of patients with stroke both ischaemic and haemorrhagic. A total of 97 patients of stroke confirmed by computerized tomography (CT) scan of brain were included in the study. Of them 51 were treated with levodopa 125mg (L group) and physiotherapy while 46 patients (NL group) were treated only with physiotherapy without levodopa. The patients were followed up every 2 weeks interval for 8 weeks. Motor outcome was measured in Rivermead Mobility Index (RMI). Comparison was made between L & NL group irrespective of stroke types at the end of 4th visit. Also the effect of levodopa was assessed separately in ischaemic & haemorrhaegic stroke. The results of the study showed that the age of stroke patients was 54.70+/-15.07 years in L group & 58.10+/ 14.69 years in NL group. Ischaemic stroke patients were 72% and haemorrhagic stroke patients were 28%. The mean increase RMI score in L group irrespective of stroke subtypes was 6.9 while in NL group was 3.0. The increase in motor outcome was significantly higher in levodopa group than non-levodopa group (p<0.001). Similarly motor outcome measured in RMI score were significantly better individually in ischaemic & haemorrhagic stroke patients of L group than NL (p<0.001). So, the study result concludes that low dose levodopa improves motor outcome in patient with stroke both ischaemic and haemorrhagic. PMID- 22081191 TI - Prevalence and antimicrobial susceptibility of enterococcus species isolated from clinical specimens. AB - Multidrug-resistant enterococci are emerging as a leading nosocomial pathogen. Knowledge of the antimicrobial resistance profile is essential to formulate treatment guidelines for infection caused by enterococci. A total of 200 enterococcal strains were isolated from various clinical specimens from May 2009 to April 2010 in the Department of Microbiology, Bangladesh Institute of Health Sciences Hospital, Mirpur, Dhaka, Bangladesh. They were speciated and an antimicrobial susceptibility pattern was determined. E. faecalis (75.5%) was the most common species in all clinical specimens followed by E. faecium (7.5%) and E. duranes (3.5%). Polymicrobial infection was found in 24(12%) of the cases. The maximum susceptibility was observed with vancomycin (100%) followed by linezolid (96%), imipenem and nitrofurantoin (95%). About 30% high level aminoglycoside resistance (HLAR) was found in this study. PMID- 22081192 TI - Risk factors of hepatitis B virus infection in children. AB - Hepatitis B infection (HBV) is prevalent worldwide. Overall prevalence is about 3 percent in Bangladesh. Treatments of chronic HBV infection by antiviral drugs are costly and outcome of treatment is also restricted. Therefore risk factors identification is the logical & rational approach to prevent HBV infection. This case control study aimed to find out certain risk factors related to HBV infection in children. It was conducted on patients attending the Department of Paediatric Gastroenterology & Nutrition and Department of Virology of BSMMU and Khidmah Hospital, Dhaka. A total of one hundred cases and one hundred suitably matched controls were studied between October 2007 to May 2009.Variables used for the purpose of the study were younger age, use of mosquito nets, history of undergoing surgical procedures, history of taking intravenous drug and blood transfusion, maternal infection, dental procedures and abrasion during hair cut in barber shops. Chi-square test was done to measure the level of significance. Odds ratio was calculated to correlate the disease risk. Backward conditional logistic regression was also done for multivariate analysis. The study result showed that the frequency of HBV infection among the study population was higher (62.0%) among children of 7 to 12 years age group. In younger age group (0-6 years) prevalence was 18.0%. Respondents who did not use mosquito net during sleep on a regular basis had higher risk of developing HBV infection than those who used it regularly (p value 0.028). Children who underwent surgical procedures for any reason were significantly associated with HBV infection (p value 0.005). Intravenous drug use (p value 0.001), mother to child transmission (p value 0.001) and history of abrasion during hair cut in barber shops (p value 0.04) were also identified as significant risk factors. No significant association was observed with blood transfusion (p value 0.138) and dental procedures (p value 0.315). From this study it may be concluded that irregular use of mosquito nets, history of surgical procedures, history of parenteral medication, transmission from infected mothers and abrasion during hair cut in barber shops are the probable important risk factors of HBV infection in children. PMID- 22081193 TI - Disseminated tuberculosis presenting as acute coronary syndrome. AB - Tuberculosis is a major public health problem in Bangladesh. Though tuberculosis is common but acute myopericarditis can rarely be caused by tuberculosis infection. A case of disseminated tuberculosis presenting with features of acute coronary syndrome is presenting here. A 26 years old man was admitted for severe central chest pain for 2 days and fever for 2 months. His ECG showed ST segment elevation in chest leads, V1 to V4 with elevated Troponin I and high ESR. Chest X Ray depicted an enlarged cardiac shadow. Echocardiography demonstrated multiple dynamic cavitary lesions involving interventricular septum as well as anterior wall of the left ventricle within myocardium with moderate pericardial effusion with trivial mitral regurgitation. A CT scan of chest with contrast revealed multiple calcific communicating cavities within endocardium and myocardium involving interventricular septum and anterior wall of the left ventricle of heart and multiple cavitary lesions in the mid zone of left lung with bilateral mild pleural effusion. The patient made an excellent recovery on management of acute coronary syndrome and on antitubercular therapy. PMID- 22081194 TI - Pancreatic lipomatosis with massive steatorrhea. AB - Fat replacement of the exocrine pancreas is a rare cause of exocrine pancreatic failure. We report a case of 32-year-old man with weight loss and massive steatorrhea in whom abdominal computed tomography (CT) was diagnostic of pancreatic lipomatosis. The diagnosis was confirmed by needle aspiration cytological (FNAC) examination. Then oral pancreatic enzyme replacement in association with cimetidine led to a marked reduction of steatorrhea and weight gain. In this report it is emphasized that this lipomatosis can be demonstrated by non-invasive technique using abdominal CT-scan. PMID- 22081195 TI - Osteopetrosis. AB - A 15 years old Bangladeshi boy presented with hepatosplenomegaly, anaemia, multiple fractures (symptomatic and asymptomatic) without jaundice was investigated. Laboratory findings revealed leukoerythroblastic blood picture with reduced haemoglobin (7.7 gm/dl). Skeletal survey showed generalized increased bone density, sclerosed medulary space, Rugger-Jersey spine and diploic space filled with dense materials. Overlapping clinical features of both intermediate autosomal recessive and adult autosomal dominant variety of osteopetrosis were found in this patient but diagnosis were made on the basis of typical radiological finding which was mostly consistent with the adult autosomal dominant variety. The patient was treated conservatively and specialist consultation was taken in managing bony abnormalities. This patient was discharged with advised of subsequent follow-up. PMID- 22081196 TI - Primary disseminated MDR-TB in a Bangladeshi man: a silent and emerging clinical problem for clinicians. AB - A 26 years old Bangladeshi man experienced sudden gross haematuria for 10 days when he was working in Italy in June'07 that was resolved spontaneously. Six months' later he again developed haematuria and was admitted into an Italian hospital for its evaluation and management. In the mean time, he developed low grade fever, cough, back pain, spinal angulations, walking difficulty. His X-ray chest postero-anterior view revealed cavitary lesions in upper zones of both lung fields. Intravenous Urography (IVU) was done which revealed hydronephrosis and hydroureter of left kidney. Magnetic Resonance Imaging (MRI) of dorso-lumber spine revealed collapse of D10-12 and L4-5 vertebral bodies with perivertebral and epidural abscess. Sputum and urine smear for Acid-Fast-Bacilli (AFB) demonstrated the organisms on Z-N stain and AFB culture and sensitivity demonstrated that it was resistant to isoniazide, Rifampicin and streptomycin and diagnosed as primary disseminated multi-drug Resistant tuberculosis (MDR-TB). Second-line drugs were started in Italy on 15th January'08 and were continued thereafter in National Institute of Diseases of the Chest and Hospital (NIDCH). A ureteric stent which was given in Italy to get relief of hydro-ureter was removed in Dhaka. A neurosurgery (costo-transversectomy with decompression of spine) was done in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and patient get relief of back pain paresthesia. Lastly, his sputum and urine AFB smear and AFB culture became negative. So, primary disseminated MDR-TB with renal, spinal and pulmonary involvement was diagnosed in this Bangladeshi man who had a sputum AFB culture and sensitivity during his initial diagnostic work-up in Italy. It's an alarming case that demonstrated necessity of sputum AFB culture and sensitivity during initial diagnostic work-up. PMID- 22081197 TI - Tuberculosis of knee joint and tubercular pyomyositis of gastrocnemius muscle. AB - Extra-spinal musculoskeletal tuberculosis (TB) is rare and tubercular pyomyositis is extremely rare. Tuberculosis of the knee-joint is a haematogenous infection secondary to a focus of active disease elsewhere in the body which may not be found. Tubercular pyomyositis usually caused by invasion from the adjacent structures rather than a secondary spread. Here we describe a 40 years old male patient who presented to us with pain in the right knee joint for one and half years and pain and swelling of right calf muscle for fifteen days. He was eventually diagnosed as a case of tuberculosis of the right knee joint and tubercular pyomyositis of right gastrocnemius muscle on the basis of fine needle aspiration from the right calf that showed caseation necrosis with clusters of epithelial cells despite absence of systemic symptoms, the absence of other foci of active tuberculosis and a normal chest radiograph. PMID- 22081198 TI - Bilateral, symmetrical and extensive cerebral calcification in pseudohypoparathyroidism. AB - Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by hypocalcemia, hyperphosphatemia, increased serum concentration of parathyroid hormone (PTH), and insensitivity to the biological activity of PTH. Pseudohypoparathyroidism is rare sporadic or autosomal dominant disorder having several subtypes (type Ia, Ib, Ic, type II). We report a case who was 27 years old married lady having two children presented in the summer season 2009. Her trousseau's sign was positive, serum calcium 5.5 mg/dl, PTH 137 pgm/ml and CT scan of brain shows bilateral and symmetrical calcification. She had occasional doubtful seizure and headache for 7 years. Initially clinicians could not reach the diagnosis due to inadequate investigations. PMID- 22081199 TI - Colles' fracture - is it a signal of osteoporosis? AB - Asymptomatic post-menopausal osteoporosis is common but some-times associated with pain and deformity. Symptomatic osteoporosis is usually associated with fracture. A 59 years old post-menopausal woman presented with a history of acute low-back-pain. She had menopause for 12 years. She gave history of colles' fracture at about two years back. Her mother died as consequences of femoral neck fracture. MRI of vertebral spine showed demineralization with partial collapse of D6,7,12 and L1 vertebra. Dual energy X-ray absorptiometry of vertebra showed BMD T-score of -4.5. Patient was managed with IV infusion of zoledronic acid, oral intake of vitamin D and calcium supplements and with regular non-weight-bearing exercises. Her condition improved gradually. During post-menopausal period, every women must be aware of osteoporosis and any fracture in that time must be evaluated to rule out osteoporosis. PMID- 22081200 TI - Papillon-Lefevre syndrome. AB - Papillon-Lefevre syndrome is a very rare syndrome of autosomal recessive inheritance characterized by palmoplanter hyperkeratosis of the skin and severe periodontal disease extending to destruction of the alveolar bone surrounding deciduous and permanent teeth as they erupt leading to precocious loss of dentition. Although the exact pathogenesis of this syndrome is still unknown immunologic, microbiologic, and genetic bases have been proposed. Here we report a case of Papillon-Lefevre syndrome. The patient had generalized plaque accumulation along with halitosis, mobile teeth with periodontal pocket with pus exudation. Blood & biochemical report was within normal limit with a low CD3+ and CD4+. PMID- 22081201 TI - An overview of Brucellosis. AB - Brucellosis is the most important zoonotic disease caused by Brucella species comprising Gram negative, facultative, intracellular pathogens. The true incidence of human brucellosis is unknown for most countries of the world including Bangladesh. But brucellosis is not uncommon in our country. Due to its increasing incidence in many countries of the world it is an important issue now days. Domestic animals such as cattle, goats, sheep, pigs, camel, buffalo and dogs serve as a reservoir hosts. Transmission of brucellosis to humans occurs through the consumption of infected, unpasteurized animal milk and milk products, through direct contact with infected animal parts, through ruptures of skin and mucous membranes and through the inhalation of infected aerosolized particles. Due to variability of clinical features and limited availability of laboratory facilities, the disease remains largely under-reported. Early and specific diagnosis is important to ensure a favourable outcome regarding this zoonotic disease. PMID- 22081202 TI - Guillian-Barre syndrome. AB - Guillian-Barre syndrome (GBS) is the most common cause of acute flaccid paralysis. All age groups can be affected, more common in elderly. Campylobacter jejuni, a major cause of bacterial gastroenteritis worldwide has become recognized as a most frequent antecedent pathogen for GBS. A prospective case controlled study showed, positive C. Jejuni serology was found in an unprecedented high frequency of 57% as compared to 8% in family controls and 3% in control patients with other neurological diseases. In GBS there is molecular mimicry between epitops found in the cell walls of some micro-organisms and gangliosides in schwann cell membrane. Diagnosis is mainly clinical. The mainstay of treatment of GBS is supportive care and prevention of complications. Respiratory failure and autonomic dysfunction are the common causes of death from GBS. Plasma exchange and intravenous immunoglobulin therapy shorten the duration of ventilation and improve prognosis. Overall, prognosis of GBS is good. Eighty percent of patients recover completely within 3-6 months, 4% die, and the remainder suffers residual neurological disability. GBS may be prevented by development of a vaccine against C. Jejuni. Early and specific diagnosis is important to ensure a favourable outcome. PMID- 22081203 TI - Ad-hoc percutaneous coronary intervention and staged percutaneous coronary intervention. AB - Percutaneous coronary intervention (PCI) is a catheter based procedure where a catheter system is introduced through a systemic artery under local anesthesia in a stenotic coronary artery by controlled inflation of a distensible balloon. At early period, PCI was done in a separate session following coronary angiogram (Staged PCI) and it was more costly and hospital stay was long. As the expertization and laboratory facilities improved, the health care providers think about cost, hospital stay and patient convenience. So, to reduce the cost and patient preferred more PCI being done immediately following diagnostic catheterization (Ad-hoc PCI). Subsequently this Ad-hoc procedure becomes popular and now most of the PCI are Ad-hoc PCI worldwide. Rate of combined procedure (Ad hoc) progressively increased from 54% in 1990 to 88% in 2000 with a significant decrease in rate of complications. In the initial study of Ad-hoc PCI suggested that Ad-hoc PCI should be done in selected group of patients as there was some potential risk factors (e.g. Multivessel diseases, unstable angina, aortic valve disease, and recent infarction or thrombolytic therapy) for Ad-hoc procedure and some (e.g. Older age, multivessel PTCA and complex lesion PTCA) for staged procedure. But recent studies showed that no significant difference in respect of safety and efficacy between Ad-hoc and staged PCI. Previous studies, in the era of balloon angioplasty from 1985 to 1995, Haraphonges et al. (1988), Rozenman et al. (1995) and Kimmel et al. (1997) suggested that an ad hoc approach is safe, with potentially more complications in patients with unstable angina pectoris or other high-risk factors. However, these reports have been limited to observational studies representing single institution experiences with small samples and inclusion of patients who underwent emergency PCI procedures. In Bangladesh a prospective observational study was done among 120 patients to compare the outcome of Ad-hoc and staged PCI and high angiographic, procedural and clinical success rate with minimum complications were observed in Ad-hoc PCI in comparison to Staged PCI. PMID- 22081204 TI - The role of neuropsychological assessment in the functional outcomes of children with ADHD. AB - The value of evidence-based services is now recognized both within clinical communities and by the public at large. Increasingly, neuropsychologists must justify the necessity of often costly and time-consuming neuropsychological assessments in the diagnosis and treatment of common childhood disorders, such as Attention-deficit/Hyperactivity Disorder (ADHD). Published medical guidelines and prominent researchers, however, have argued against the need for formal neuropsychological assessment of ADHD. The present review examines the literature on developmental outcomes in childhood ADHD, with emphasis on the utility of formal neuropsychological assessment among children diagnosed and treated in primary care settings. The review yields three central findings: 1) adherence to published diagnostic guidelines for ADHD is poor among pediatric and primary care physicians; 2) ADHD most often co-exists with other disorders, thus diagnoses made without formal psychometric assessment can be incomplete or incorrect, ultimately increasing treatment costs; and, 3) untreated children with ADHD, and those who have untreated comorbidities, are at greater risk for poor outcomes in social, academic, vocational, and practical settings. The available literature suggests that neuropsychological assessment provides information that can potentially reduce risks for poor outcomes and improve quality of life among children with ADHD. Controlled studies directly examining the impact of neuropsychological assessments in improving outcomes among children with ADHD are needed. PMID- 22081205 TI - Amerindians normalized waist circumference and obesity diagnosis standarized by biochemical and HLA data. AB - Metabolic syndrome (MS) and obesity are principal causes of morbidity all over the World, particularly for their association to cardiovascular risk. Amerindians are often living in countries and remote areas with unavailable sophisticated diagnoses methodologies. However, waist-circumference is a reliable and easy to record parameter of visceral obesity and MS. Waist circumference normal values are not yet established in Amerindians: South Asian and Japanese values have been recommended for Amerindian use. The purpose of this study is to objectively define for the first time the waist circumference measure cut-off points for Amerindians. A total of 303 unrelated Amerindian adults recently immigrated to Madrid were studied; they were healthy, since they were questioned and tested as appropriate for blood donation. Waist-circumference was measured in these voluntary blood donors after written consent. Chosen subjects for study had HLA quasi-specific Amerindian genes and not gained weight since their relatively short time living in Spain. Amerindians with Type I or II diabetes or family antecedents were removed from the study. The biochemical parameter used to define normality for MS was the reliable serum HDL-cholesterol levels, whose values are diet independent. A Receiver Operating Characteristic analysis was used to compare the predictive validity and to find out the optimal cut-off points of waist circumference normal values. Cut-off points were <=88.5 cm in males and <=82.5 cm in females; these values were close to the median values (88 and 82.2 cm, respectively). Obtained waist circumference values recorded here in normal Amerindians are different to those previously recommended indirectly (those of South Asian/Japanese populations). These parameters may be of great value for American countries health care in order to predict and control MS and its cardiovascular complications. Other countries having a heavy Amerindian immigration (i.e.: USA, Spain) may also benefit for establishing specific Preventive Medicine programs. PMID- 22081206 TI - Swallowing, nutrition and patient-rated functional outcomes at 6 months following two non-surgical treatments for T1-T3 oropharyngeal cancer. AB - PURPOSE: Altered fractionation radiotherapy with concomitant boost (AFRT-CB) may be considered an alternative treatment for patients not appropriate for chemoradiation (CRT). As functional outcomes following AFRT-CB have been minimally reported, this exploratory paper describes the outcomes of patients managed with AFRT-CB or CRT at 6 months post-treatment. METHODS: Using a cross sectional analysis design, functional outcomes of 14 AFRT-CB and 17 CRT patients with T1-T3 oropharyngeal cancers were explored at 6 months post-treatment. Clinical and instrumental swallow assessments, weight and nutritional status, and the functional impact of treatment were examined. RESULTS: Inferior outcomes were observed for the CRT patients on the RBHOMS (p = 0.03) which was reflected in diet and fluid restrictions with 18% of the CRT group requiring modified fluids and diets. Although a trend (p = 0.07) was noted for increased lingual deficits and aspiration risk for fluids in the CRT group, no other significant differences were observed. Both groups experienced an average of 10 kg weight loss and reported reduced general and swallowing-related function. CONCLUSIONS: These preliminary data suggest functional outcomes following AFRT-CB and CRT were largely comparable at 6 months post-treatment. Treatment intensification in any form may contribute to impaired function which requires multidimensional intervention. Larger cohort investigations with systematic methodology are needed to further examine these initial findings. PMID- 22081207 TI - Increased oxidative stress in preschool children exposed to passive smoking. AB - OBJECTIVES: To study the effect of passive cigarette smoking on plasma oxidative and antioxidative status in passive smoking preschool children and to compare them with controls. METHODS: Thirty-four passive smoking (five to 50 cigarettes per day) preschool children (study group) and 32 controls who had never been exposed to cigarette smoke were randomly chosen from children aged from 4 to 6 years. Urinary cotinine and plasma indicators of oxidative and antioxidative status, i.e., total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI), were determined. RESULTS: Mean environmental cigarette consumption was 22+/-13 cigarettes per day in passive smoking children. Mean urinary cotinine levels were 77.6+/-41.4 ng/mL and 11.9+/-2.3 ng/mL in the study and control groups, respectively (p < 0.001). Mean plasma TAC levels were 0.95+/-0.13 mmol Trolox equivalent/L and 1.01+/-0.09 mmol Trolox equivalent/L, respectively (p = 0.039). Mean plasma TOS levels were 28.6+/-7.9 umol H2O2 equivalent/L and 18.5+/-6.3 umol H2O2 equivalent/L, respectively (p < 0.001). Mean OSI levels were 3.08+/-0.98 arbitrary units and 1.84+/-0.64 arbitrary units, respectively (p < 0.001). A small amount of cigarette smoke (five to 10 cigarettes per day) causes considerable oxidative stress. There were significant correlations between number of cigarettes consumed and oxidant status and OSI levels. CONCLUSIONS: Passive smoke is a potent oxidant in preschool children. Its deleterious effects are not limited just to heavy passive smoking, but also occur with exposure to small amounts of smoke. PMID- 22081210 TI - Dependence on the F0F1-ATP synthase for the activities of the hydrogen-oxidizing hydrogenases 1 and 2 during glucose and glycerol fermentation at high and low pH in Escherichia coli. AB - Escherichia coli has four [NiFe]-hydrogenases (Hyd); three of these, Hyd-1, Hyd-2 and Hyd-3 have been characterized well. In this study the requirement for the F(0)F(1)-ATP synthase for the activities of the hydrogen-oxidizing hydrogenases Hyd-1 and Hyd-2 was examined. During fermentative growth on glucose at pH 7.5 an E. coli F(0)F(1)-ATP synthase mutant (DK8) lacked hydrogenase activity. At pH 5.5 hydrogenase activity was only 20% that of the wild type. Using in-gel activity staining, it could be demonstrated that both Hyd-1 and Hyd-2 were essentially inactive at these pHs, indicating that the residual activity at pH 5.5 was due to the hydrogen-evolving Hyd-3 enzyme. During fermentative growth in the presence of glycerol, hydrogenase activity in the mutant was highest at pH 7.5 attaining a value of 0.76 U/mg, or ~50% of wild type activity, and Hyd-2 was only partially active at this pH, while Hyd-1 was inactive. Essentially no hydrogenase activity was measured at pH 5.5 during growth with glycerol. At this pH the mutant had a hydrogenase activity that was maximally only ~10% of wild type activity with either carbon substrate but a weak activity of both Hyd-1 and Hyd-2 could be detected. Taken together, these results demonstrate for the first time that the activity of the hydrogen-oxidizing hydrogenases in E. coli depends on an active F(0)F(1)-ATP synthase during growth at high and low pH. PMID- 22081209 TI - SOD1 and mitochondria in ALS: a dangerous liaison. AB - Mutant Cu,Zn superoxide dismutase (mutSOD1) is found in a subset of patients with familial amyotrophic lateral sclerosis (ALS), a fatal progressive paralysis due to loss of motor neurons. In the present article, we review existing evidence linking the expression of mutSOD1 to the many facets of mitochondrial dysfunction in ALS, with a focus on recent studies suggesting that the association and misfolding of the mutant protein (and possibly of the wild type protein as well) within these organelles is causally linked to their functional and structural alterations. Energy deficit, calcium mishandling and oxidative stress are paralleled by alteration in mitochondrial motility, dynamics and turnover and most probably lead to mitochondria-dependent cell death. Thus, the development of new, selective mitochondria-targeted therapies may constitute a promising approach in the treatment of SOD1-linked ALS. PMID- 22081211 TI - A comparative assessment of mitochondrial function in epimastigotes and bloodstream trypomastigotes of Trypanosoma cruzi. AB - Trypanosoma cruzi is a hemoflagellate protozoan that causes Chagas' disease. The life cycle of T. cruzi is complex and involves different evolutive forms that have to encounter different environmental conditions provided by the host. Herein, we performed a functional assessment of mitochondrial metabolism in the following two distinct evolutive forms of T. cruzi: the insect stage epimastigote and the freshly isolated bloodstream trypomastigote. We observed that in comparison to epimastigotes, bloodstream trypomastigotes facilitate the entry of electrons into the electron transport chain by increasing complex II-III activity. Interestingly, cytochrome c oxidase (CCO) activity and the expression of CCO subunit IV were reduced in bloodstream forms, creating an "electron bottleneck" that favored an increase in electron leakage and H(2)O(2) formation. We propose that the oxidative preconditioning provided by this mechanism confers protection to bloodstream trypomastigotes against the host immune system. In this scenario, mitochondrial remodeling during the T. cruzi life cycle may represent a key metabolic adaptation for parasite survival in different hosts. PMID- 22081212 TI - Molecular differential expression of voltage-gated sodium channel alpha and beta subunit mRNAs in five different mammalian cell lines. AB - Voltage-gated sodium channels are composed of one alpha subunit and one or more auxiliary beta subunits. A standard reverse transcription-polymerase chain reaction assay was used to detect the mRNAs encoding for seven alpha subunits (Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.6, Nav1.9) and for the two non covalently linked beta1 and beta3 auxiliary subunits in five different cell lines from rat, mouse and human origin. A semi-quantitavive RT-PCR analysis allowed to evaluate in each cell line, the relative expression level of each NaCh subunit previously detected. The expression profile of the cell lines was compared with that obtained from rat and mouse neural, skeletal muscle and cardiac tissues. This data provide a standard for the study of the modulation of the sodium channel expression in mammalian excitable tissues. PMID- 22081213 TI - Mapping nanomechanical properties of live cells using multi-harmonic atomic force microscopy. AB - The nanomechanical properties of living cells, such as their surface elastic response and adhesion, have important roles in cellular processes such as morphogenesis, mechano-transduction, focal adhesion, motility, metastasis and drug delivery. Techniques based on quasi-static atomic force microscopy techniques can map these properties, but they lack the spatial and temporal resolution that is needed to observe many of the relevant details. Here, we present a dynamic atomic force microscopy method to map quantitatively the nanomechanical properties of live cells with a throughput (measured in pixels/minute) that is ~10-1,000 times higher than that achieved with quasi static atomic force microscopy techniques. The local properties of a cell are derived from the 0th, 1st and 2nd harmonic components of the Fourier spectrum of the AFM cantilevers interacting with the cell surface. Local stiffness, stiffness gradient and the viscoelastic dissipation of live Escherichia coli bacteria, rat fibroblasts and human red blood cells were all mapped in buffer solutions. Our method is compatible with commercial atomic force microscopes and could be used to analyse mechanical changes in tumours, cells and biofilm formation with sub-10 nm detail. PMID- 22081214 TI - One- and two-dimensional photonic crystal microcavities in single crystal diamond. AB - Diamond is an attractive material for photonic quantum technologies because its colour centres have a number of outstanding properties, including bright single photon emission and long spin coherence times. To take advantage of these properties it is favourable to directly fabricate optical microcavities in high quality diamond samples. Such microcavities could be used to control the photons emitted by the colour centres or to couple widely separated spins. Here, we present a method for the fabrication of one- and two-dimensional photonic crystal microcavities with quality factors of up to 700 in single crystal diamond. Using a post-processing etching technique, we tune the cavity modes into resonance with the zero phonon line of an ensemble of silicon-vacancy colour centres, and we measure an intensity enhancement factor of 2.8. The controlled coupling of colour centres to photonic crystal microcavities could pave the way to larger-scale photonic quantum devices based on single crystal diamond. PMID- 22081215 TI - Ripple induced changes in the wavefunction of graphene: an example of a fundamental symmetry breaking. AB - Ideally, graphene may be regarded as a strictly 2-D structure. However, as it exists in a 3-D world, perturbations often distort this ideal 2-D structure. Under a variety of conditions graphene has been shown to develop ripples, which may have undesirable consequences for a variety of properties of graphene, such as electron transport. In addition to this, it has been speculated that ripples may be an intrinsic property of graphene, and it has also been suggested that unlocking the secrets of these ripples could be useful in the search for (an understanding of) the elusive Higgs boson. However, ripples in graphene can only be avoided, or utilized, if they can be reproducibly detected. Here we explore the most fundamental aspect of these ripples, that is, the effect of a static ripple structure on various properties of large graphene nanoflakes. We find that the mechanical, thermodynamic and electronic properties are unaltered by this fundamental rippling, but this spontaneous symmetry breaking induces a significant change in the structure of the wavefunction. This profound effect occurs only at the most basic level, but it should be, in principle, experimentally observable. PMID- 22081216 TI - Response shift in patients with multiple sclerosis: an application of three statistical techniques. AB - OBJECTIVE: With the evolution of theory and methods for detecting recalibration, reprioritization, and reconceptualization response shifts, the time has come to evaluate and compare the current statistical detection techniques. This manuscript presents an overview of a cross-method validation done on the same patient sample. METHODS: Three statistical techniques were used: Structural Equation Modeling, Latent Trajectory Analysis, and Recursive Partitioning and Regression Tree modeling. The study sample (n = 3,008) was drawn from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry to represent patients soon after diagnosis, classified as having either a self-reported relapsing, progressive, or stable disease trajectory. Patient-reported outcomes included the disease-specific Performance Scales and the Patient-Derived Disease Steps, and the generic SF-12v2 measure. RESULTS: Small response shift effect sizes were detected by all of the methods. Recalibration response shift was detected by Structural Equation Modeling, Recursive Partitioning Regression Tree demonstrated patterns consistent with all three types of response shift, and Latent Trajectory Analysis, although unable to distinguish types of response shift, did detect response shift in less than 1% of the sample. CONCLUSION: The methods and their findings were discussed for operationalization, interpretability, assumptions, ability to use all data points from the study sample, limitations, and strengths. Directions for future research are discussed. PMID- 22081217 TI - Validity and reliability of Persian version of Chronic Liver Disease Questionnaire (CLDQ). AB - PURPOSE: The aim of this study is to test the psychometric properties of the Persian version of the Chronic Liver Disease Questionnaire (CLDQ) in Iranian candidates for liver transplantation. METHOD: One hundred and fifty-five consecutive adult patients awaiting liver transplantation completed the Persian version of CLDQ and the short-form health survey (SF-36). The etiology of cirrhosis, Child Pugh classification and Model for End stage Liver Disease (MELD) scores were taken from medical records. RESULTS: The scaling success rate for convergent validity was 100% for all domains, and the success rate for item discriminant validity was 95.8% (139/145). The internal consistency (Cronbach alpha) for the domains ranged from 0.65 to 0.89. Multitrait-multimethod correlation matrix and factor analysis revealed that the CLDQ and SF-36 measure different constructs of quality of life. CONCLUSION: The Persian version of the CLDQ, a disease-specific questionnaire for measuring health-related quality of life, is accepted by liver transplantation candidates with adequate reliability and validity. There is no significant correlation of Child Pugh classification and MELD score with quality of life. PMID- 22081218 TI - 'All the burden on all the carers': exploring quality of life with family caregivers of Huntington's disease patients. AB - BACKGROUND: Existing research suggests that family caregivers of persons with Huntington's disease face a unique series of problems, linked to the complex nature of the disease. There is little research that explicitly investigates the impact of HD on the quality of life (QoL) of the family caregiver. The purpose of this study was to explore the quality of life issues for family carers of Huntington's disease patients in a focus group setting. METHODS: Participants were recruited via a Huntington's Disease Association (HDA) family conference day. Six semi-directed focus groups (n = 47) explored disease-specific aspects of QoL that were deemed important to family carers of this carer group. Data were analysed using Interpretative Phenomenological Analysis (IPA). RESULTS: Analysis of the focus group data identified four superordinate themes: 'Levels of Support', 'Dissatisfaction with Caregiving Role', 'Practical Aspects of Caring' and 'Feelings and Emotional Well-being'. CONCLUSIONS: These data provide evidence that QoL is compromised in many ways for HD family carers. The carers in this study often negated their own needs as their caregiving role overwhelmed them and 'took over' their lives. PMID- 22081220 TI - The National Center for Biomedical Ontology. AB - The National Center for Biomedical Ontology is now in its seventh year. The goals of this National Center for Biomedical Computing are to: create and maintain a repository of biomedical ontologies and terminologies; build tools and web services to enable the use of ontologies and terminologies in clinical and translational research; educate their trainees and the scientific community broadly about biomedical ontology and ontology-based technology and best practices; and collaborate with a variety of groups who develop and use ontologies and terminologies in biomedicine. The centerpiece of the National Center for Biomedical Ontology is a web-based resource known as BioPortal. BioPortal makes available for research in computationally useful forms more than 270 of the world's biomedical ontologies and terminologies, and supports a wide range of web services that enable investigators to use the ontologies to annotate and retrieve data, to generate value sets and special-purpose lexicons, and to perform advanced analytics on a wide range of biomedical data. PMID- 22081219 TI - The National Alliance for Medical Image Computing, a roadmap initiative to build a free and open source software infrastructure for translational research in medical image analysis. AB - The National Alliance for Medical Image Computing (NA-MIC), is a multi institutional, interdisciplinary community of researchers, who share the recognition that modern health care demands improved technologies to ease suffering and prolong productive life. Organized under the National Centers for Biomedical Computing 7 years ago, the mission of NA-MIC is to implement a robust and flexible open-source infrastructure for developing and applying advanced imaging technologies across a range of important biomedical research disciplines. A measure of its success, NA-MIC is now applying this technology to diseases that have immense impact on the duration and quality of life: cancer, heart disease, trauma, and degenerative genetic diseases. The targets of this technology range from group comparisons to subject-specific analysis. PMID- 22081221 TI - The Center for Computational Biology: resources, achievements, and challenges. AB - The Center for Computational Biology (CCB) is a multidisciplinary program where biomedical scientists, engineers, and clinicians work jointly to combine modern mathematical and computational techniques, to perform phenotypic and genotypic studies of biological structure, function, and physiology in health and disease. CCB has developed a computational framework built around the Manifold Atlas, an integrated biomedical computing environment that enables statistical inference on biological manifolds. These manifolds model biological structures, features, shapes, and flows, and support sophisticated morphometric and statistical analyses. The Manifold Atlas includes tools, workflows, and services for multimodal population-based modeling and analysis of biological manifolds. The broad spectrum of biomedical topics explored by CCB investigators include the study of normal and pathological brain development, maturation and aging, discovery of associations between neuroimaging and genetic biomarkers, and the modeling, analysis, and visualization of biological shape, form, and size. CCB supports a wide range of short-term and long-term collaborations with outside investigators, which drive the center's computational developments and focus the validation and dissemination of CCB resources to new areas and scientific domains. PMID- 22081222 TI - Simbios: an NIH national center for physics-based simulation of biological structures. AB - Physics-based simulation provides a powerful framework for understanding biological form and function. Simulations can be used by biologists to study macromolecular assemblies and by clinicians to design treatments for diseases. Simulations help biomedical researchers understand the physical constraints on biological systems as they engineer novel drugs, synthetic tissues, medical devices, and surgical interventions. Although individual biomedical investigators make outstanding contributions to physics-based simulation, the field has been fragmented. Applications are typically limited to a single physical scale, and individual investigators usually must create their own software. These conditions created a major barrier to advancing simulation capabilities. In 2004, we established a National Center for Physics-Based Simulation of Biological Structures (Simbios) to help integrate the field and accelerate biomedical research. In 6 years, Simbios has become a vibrant national center, with collaborators in 16 states and eight countries. Simbios focuses on problems at both the molecular scale and the organismal level, with a long-term goal of uniting these in accurate multiscale simulations. PMID- 22081223 TI - Using systems and structure biology tools to dissect cellular phenotypes. AB - The Center for the Multiscale Analysis of Genetic Networks (MAGNet, http://magnet.c2b2.columbia.edu) was established in 2005, with the mission of providing the biomedical research community with Structural and Systems Biology algorithms and software tools for the dissection of molecular interactions and for the interaction-based elucidation of cellular phenotypes. Over the last 7 years, MAGNet investigators have developed many novel analysis methodologies, which have led to important biological discoveries, including understanding the role of the DNA shape in protein-DNA binding specificity and the discovery of genes causally related to the presentation of malignant phenotypes, including lymphoma, glioma, and melanoma. Software tools implementing these methodologies have been broadly adopted by the research community and are made freely available through geWorkbench, the Center's integrated analysis platform. Additionally, MAGNet has been instrumental in organizing and developing key conferences and meetings focused on the emerging field of systems biology and regulatory genomics, with special focus on cancer-related research. PMID- 22081224 TI - iDASH: integrating data for analysis, anonymization, and sharing. AB - iDASH (integrating data for analysis, anonymization, and sharing) is the newest National Center for Biomedical Computing funded by the NIH. It focuses on algorithms and tools for sharing data in a privacy-preserving manner. Foundational privacy technology research performed within iDASH is coupled with innovative engineering for collaborative tool development and data-sharing capabilities in a private Health Insurance Portability and Accountability Act (HIPAA)-certified cloud. Driving Biological Projects, which span different biological levels (from molecules to individuals to populations) and focus on various health conditions, help guide research and development within this Center. Furthermore, training and dissemination efforts connect the Center with its stakeholders and educate data owners and data consumers on how to share and use clinical and biological data. Through these various mechanisms, iDASH implements its goal of providing biomedical and behavioral researchers with access to data, software, and a high-performance computing environment, thus enabling them to generate and test new hypotheses. PMID- 22081225 TI - A translational engine at the national scale: informatics for integrating biology and the bedside. AB - Informatics for integrating biology and the bedside (i2b2) seeks to provide the instrumentation for using the informational by-products of health care and the biological materials accumulated through the delivery of health care to conduct discovery research and to study the healthcare system in vivo. This complements existing efforts such as prospective cohort studies or trials outside the delivery of routine health care. i2b2 has been used to generate genome-wide studies at less than one tenth the cost and one tenth the time of conventionally performed studies as well as to identify important risk from commonly used medications. i2b2 has been adopted by over 60 academic health centers internationally. PMID- 22081226 TI - Distribution of prolactin receptors suggests an intraductal role for prolactin in the mouse and human mammary gland, a finding supported by analysis of signaling in polarized monolayer cultures. AB - Despite the important role of prolactin (PRL) in mammary gland development and function, little is known about the distribution of the different forms of the prolactin receptor (PRLR) under various physiological circumstances. Here, the distribution of the long (LF) and the short (S3 in mouse) receptor common to both mice and rats was determined by immunofluorescence on frozen sections of virgin, pregnant and lactating mouse mammary gland. Myoepithelial cells were consistently and intensely stained for both receptors. For luminal cells at all stages (ducts and alveoli), a large proportion of PRLR staining was unexpectedly present on the apical face. In the non-lactating state, no basal staining of luminal cells was detectable. During lactation, a proportion of both receptors moved to the basolateral surface. In vitro, HC11 cells showed constitutive expression of LF but expression of S3 only upon the formation of adherent junctions. Tight junction formation was accelerated by incubation in pseudo-phosphorylated PRL, as measured by transepithelial resistance and the expression and placement of the tight junction protein, zonula occludens-1. Once an intact monolayer had formed, all LF and S3 receptors were apical (akin to the non-lactating state) and only apical application of PRL activated the Jak2-STAT5 and ERK pathways. By contrast, basolateral application of PRL resulted in a reduction in basal ERK phosphorylation, suggesting an involvement of a dual specificity protein phosphatase. Normal human breast samples also showed apical PRLRs. These results demonstrate important contextual aspects of PRL-PRLR interactions with implications for the analysis of the role of PRL in breast cancer. PMID- 22081227 TI - Predicting phenotypic variation in yeast from individual genome sequences. AB - A central challenge in genetics is to predict phenotypic variation from individual genome sequences. Here we construct and evaluate phenotypic predictions for 19 strains of Saccharomyces cerevisiae. We use conservation-based methods to predict the impact of protein-coding variation within genes on protein function. We then rank strains using a prediction score that measures the total sum of function-altering changes in different sets of genes reported to influence over 100 phenotypes in genome-wide loss-of-function screens. We evaluate our predictions by comparing them with the observed growth rate and efficiency of 15 strains tested across 20 conditions in quantitative experiments. The median predictive performance, as measured by ROC AUC, was 0.76, and predictions were more accurate when the genes reported to influence a trait were highly connected in a functional gene network. PMID- 22081229 TI - Parallel bacterial evolution within multiple patients identifies candidate pathogenicity genes. AB - Bacterial pathogens evolve during the infection of their human host(1-8), but separating adaptive and neutral mutations remains challenging(9-11). Here we identify bacterial genes under adaptive evolution by tracking recurrent patterns of mutations in the same pathogenic strain during the infection of multiple individuals. We conducted a retrospective study of a Burkholderia dolosa outbreak among subjects with cystic fibrosis, sequencing the genomes of 112 isolates collected from 14 individuals over 16 years. We find that 17 bacterial genes acquired nonsynonymous mutations in multiple individuals, which indicates parallel adaptive evolution. Mutations in these genes affect important pathogenic phenotypes, including antibiotic resistance and bacterial membrane composition and implicate oxygen-dependent regulation as paramount in lung infections. Several genes have not previously been implicated in pathogenesis and may represent new therapeutic targets. The identification of parallel molecular evolution as a pathogen spreads among multiple individuals points to the key selection forces it experiences within human hosts. PMID- 22081228 TI - Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease. AB - Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 * 10( 11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 * 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 * 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease. PMID- 22081230 TI - Partial adenosine A1 receptor agonists for cardiovascular therapies. AB - Adenosine, a purine nucleoside, is present in all cells in tightly regulated concentrations. It has many different physiological effects in the whole body and in the heart. Adenosine activates four G protein-coupled receptors A1, A2a, A2b, and A3. Activation of myocardial A1 receptors has been shown to inhibit a variety of myocardial pathologies associated with ischemia and reperfusion injury, including stunning, arrhythmogenesis, coronary and ventricular dysfunction, acute myocardial infarction, apoptosis, and chronic heart failure, implying several options for new cardiovascular therapies for diseases, like angina pectoris, control of cardiac rhythm, ischemic injury during an acute coronary syndrome, or heart failure. However, the main issue of using full A1 receptor agonists in such indications is the broad physiologic spectrum of cardiac and extracardiac effects. Desired A1 receptor-mediated protective and regenerative cardiovascular effects might be counter-regulated by unintended side effects when considering full A1 receptor agonists. These effects can be overcome by partial A1 agonists. Partial A1 agonists can be used to trigger only some of the physiological responses of receptor activation depending on endogenous adenosine levels and on receptor reserve in different tissues. CV-Therapeutics reported the identification of a partial A1 receptor agonist CVT-3619, and recently, another partial A1 receptor agonist VCP28 was published. Both compounds are adenosine derivatives. Adenosine-like A1 receptor agonists often have the drawback of a short half-life and low bioavailability, making them not suitable for chronic oral therapy. We identified the first non-adenosine-like partial A1 receptor agonist(s) with pharmacokinetics optimal for oral once daily treatment and characterized the qualities of the partial character of the A1 receptor agonist(s) in preclinical and clinical studies. PMID- 22081231 TI - Ocular and oral grading of mucous membrane pemphigoid. AB - BACKGROUND: A variety of methods have been described for grading ocular mucous membrane pemphigoid (MMP), each with their own limitations. In contrast, there are no reported grading systems for involvement of the oral mucosa. We wished to evaluate two ocular (one established and one proposed) and an oral mucosal grading system for MMP. METHODS: Patients with MMP were assessed by three ophthalmologists and two oral medicine physicians. Ocular disease was graded using the system described by Rowsey and a proposed system based on measurement of vertical depth and horizontal width measured from the bulbar conjunctival aspect. Oral assessment used a 'mucosal disease severity score' originally described for lichen planus, in which 17 areas of the mouth are scored for involvement, together with a pain score. Levels of agreement were evaluated using Fleiss' Kappa Statistic (k). RESULTS: Forty-four patients with MMP encompassing mild to severe disease were included. Good levels of agreement were observed between observers for both vertical (k:0.86) (upper 95% CI: 1.03 mm) and horizontal (k:0.80) (upper 95% CI: 3.01 mm) involvement for the proposed ocular system and the Rowsey system (k: 0.83) (upper 95% confidence interval: 3.19 mm). There was a high coefficient of determination (R(2)) between the ocular grading systems (0.81, p < 0.01). Oral grading showed excellent levels of agreement (k: 0.71) between observers. There was no significant association between the severity of oral and ocular disease using described grading systems. CONCLUSIONS: The proposed grading systems for both oral and ocular involvement in MMP are easy to use, and show good agreement between observers. The proposed ocular system correlates well with a currently used system, and overcomes some of the difficulties encountered with existing systems. For the individual patient, changes greater than 1.5 mm (vertical) and 3 mm (horizontal) are significant. This may increase our ability to detect change or disease progression. Although the risk of ocular involvement in patients with only oral involvement has been demonstrated, the severity of oral and ocular disease are not well-correlated, due in part to an absence of an ocular disease activity score. PMID- 22081233 TI - XANES and XPS investigations of the local structure and final-state effects in amorphous metal silicates: (ZrO2)(x)(TiO2)(y)(SiO2)(1-x-y). AB - Amorphous quaternary [(ZrO(2))(x)(TiO(2))(y)(SiO(2))(1-x-y)] and ternary [(ZrO(2))(x)(SiO(2))(1-x)] silicates were synthesized using a sol-gel method and examined via XPS and XANES. Metal silicates are important industrial materials, though structural characterization is complicated because of their amorphous nature. Hard (Ti K- and Zr K-edge) and soft (Ti L(2,3)-edge) X-ray XANES spectra suggest the Ti and Zr coordination numbers in the quaternary silicates remain constant as the metal identity or total metal content (x, y, or x + y in the chemical formula) is varied. XPS core-line spectra from the quaternary silicates show large decreases in Ti 2p(3/2), Zr 3d(5/2), Si 2p(3/2), and O 1s binding energies due to increasing final-state relaxation with greater next-nearest neighbour substitution of Si for less-electronegative Ti/Zr, which was confirmed by analysis of the O Auger parameter. These decreases in binding energy occur without any changes in the ground-state energies (e.g., oxidation state) of these atoms, as examined by Ti L(2,3)-edge, Si L(2,3)-edge, and O K-edge XANES. Because most spectroscopic investigations are concerned with ground-state properties, knowledge of the contributions from final-state effects is important to understand the spectra from materials of interest. PMID- 22081232 TI - Proteomic profiling of human retinal pigment epithelium exposed to an advanced glycation-modified substrate. AB - PURPOSE: The retinal pigment epithelium (RPE) and underlying Bruch's membrane undergo significant modulation during ageing. Progressive, age-related modifications of lipids and proteins by advanced glycation end products (AGEs) at this cell-substrate interface have been implicated in RPE dysfunction and the progression to age-related macular degeneration (AMD). The pathogenic nature of these adducts in Bruch's membrane and their influence on the overlying RPE remains unclear. This study aimed to identify alterations in RPE protein expression in cells exposed to AGE-modified basement membrane (AGE-BM), to determine how this "aged" substrate impacts RPE function and to map the localisation of identified proteins in ageing retina. METHODS: Confluent ARPE-19 monolayers were cultured on AGE-BM and native, non-modified BM (BM). Following 28 day incubation, the proteome was profiled using 2-dimensional gel electrophoresis (2D), densitometry and image analysis was employed to map proteins of interest that were identified by electrospray ionisation mass spectrometry (ESI MS/MS). Immunocytochemistry was employed to localise identified proteins in ARPE-19 monolayers cultured on unmodified and AGE-BM and to analyze aged human retina. RESULTS: Image analysis detected altered protein spot densities between treatment groups, and proteins of interest were identified by LC ESI MS/MS which included heat-shock proteins, cytoskeletal and metabolic regulators. Immunocytochemistry revealed deubiquitinating enzyme ubiquitin carboxyterminal hydrolase-1 (UCH-L1), which was upregulated in AGE-exposed RPE and was also localised to RPE in human retinal sections. CONCLUSIONS: This study has demonstrated that AGE-modification of basement membrane alters the RPE proteome. Many proteins are changed in this ageing model, including UCHL-1, which could impact upon RPE degradative capacity. Accumulation of AGEs at Bruch"s membrane could play a significant role in age related dysfunction of the RPE. PMID- 22081234 TI - Urinary and dialysate losses of vitamin D-binding protein in children on chronic peritoneal dialysis. AB - BACKGROUND: Vitamin D deficiency is widely prevalent in chronic kidney disease [CKD] patients. The aim of our study was to determine whether losses of vitamin D binding protein [VDBP] in urine and dialysate contribute to circulating 25 hydroxyvitamin D [25OHD] levels in chronic peritoneal dialysis [PD] patients. METHODS: Dialysate, serum, and urine VDBP levels were measured in 16 children on PD and compared with serum and urine VDBP in ten CKD4-5 patients. Serum VDBP levels were correlated with total circulating 25OHD and peritoneal VDBP losses. RESULTS: The mean age of the study population was 9.4 +/- 3.8 years and the median time on dialysis 7.5 (1-18) months. In CKD4-5 patients, urinary VDBP losses were >300-fold higher than seen in age-matched healthy children and correlated with urinary albumin loss (p = 0.0008). There was a significant correlation between serum VDBP and total dialysate and urine losses of VDBP (p = 0.03, r = -0.53). Dialysate VDBP losses correlate with dialysate albumin loss (p = 0.01). VDBP losses in the long daytime dwell were higher than in the overnight drain (p = 0.04). Serum VDBP levels were lower in children with a longer dialysis vintage (p = 0.0004, r = -0.77). In PD patients, the mean total loss of VDBP in dialysate and urine was 1.91 +/- 1.6 MUmol/day, equivalent to ~7% of the total circulating level of VDBP in healthy controls. There was no correlation between 25(OH)D and VDBP. CONCLUSIONS: Peritoneal VDBP losses mirror both dialysate and urinary albumin losses, and are associated with a longer dialysis vintage but do not contribute to vitamin D deficiency in children on PD. PMID- 22081235 TI - Applied patent RFID systems for building reacting HEPA air ventilation system in hospital operation rooms. AB - RFID technology, an automatic identification and data capture technology to provide identification, tracing, security and so on, was widely applied to healthcare industry in these years. Employing HEPA ventilation system in hospital is a way to ensure healthful indoor air quality to protect patients and healthcare workers against hospital-acquired infections. However, the system consumes lots of electricity which cost a lot. This study aims to apply the RFID technology to offer a unique medical staff and patient identification, and reacting HEPA air ventilation system in order to reduce the cost, save energy and prevent the prevalence of hospital-acquired infection. The system, reacting HEPA air ventilation system, contains RFID tags (for medical staffs and patients), sensor, and reacting system which receives the information regarding the number of medical staff and the status of the surgery, and controls the air volume of the HEPA air ventilation system accordingly. A pilot program was carried out in a unit of operation rooms of a medical center with 1,500 beds located in central Taiwan from Jan to Aug 2010. The results found the air ventilation system was able to function much more efficiently with less energy consumed. Furthermore, the indoor air quality could still keep qualified and hospital-acquired infection or other occupational diseases could be prevented. PMID- 22081236 TI - A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis. AB - Microdialysis can be used in parallel to deep brain stimulation (DBS) to relate biochemical changes to the clinical outcome. The aim of the study was to use the finite element method to predict the tissue volume of influence (TVI(max)) and its cross-sectional radius (r (TVImax)) when using brain microdialysis, and visualize the TVI(max) in relation to patient anatomy. An equation based on Fick's law was used to simulate the TVI(max). Factorial design and regression analysis were used to investigate the impact of the diffusion coefficient, tortuosity and loss rate on the r (TVImax). A calf brain tissue experiment was performed to further evaluate these parameters. The model was implemented with pre-(MRI) and post-(CT) operative patient images for simulation of the TVI(max) for four patients undergoing microdialysis in parallel to DBS. Using physiologically relevant parameter values, the r (TVImax) for analytes with a diffusion coefficient D = 7.5 * 10-6 cm2/s was estimated to 0.85 +/- 0.25 mm. The simulations showed agreement with experimental data. Due to an implanted gold thread, the catheter positions were visible in the post-operative images. The TVI(max) was visualized for each catheter. The biochemical changes could thereby be related to their anatomical origin, facilitating interpretation of results. PMID- 22081237 TI - Gender differences in predicting antisocial behaviors: developmental consequences of physical and relational aggression. AB - This study investigated gender differences in the relationship of early physical and relational aggression to later peer rejection and overt and covert antisocial behaviors. Significant gender differences were found indicating physically aggressive boys were more likely than girls to experience later peer rejection. Early physical aggression was related to later overt antisocial behavior for boys and girls, and more strongly for girls than for boys. Early relational aggression was not associated with later forms of antisocial behavior. In the context of early physical aggression, for boys and girls peer rejection generally served to increment risk for later overt and covert antisocial behavior in an additive fashion. The data suggest some gender specificity in the social risk processes associated with the development of early overt and covert antisocial behaviors. PMID- 22081238 TI - Sexual dimorphism in clock genes expression in human adipose tissue. AB - BACKGROUND: This study was carried out to investigate whether sex-related differences exist in the adipocyte expression of clock genes from subcutaneous abdominal and visceral fat depots in severely obese patients. METHODS: We investigated 16 morbidly obese patients, eight men and eight women (mean age 45 +/- 20 years; mean BMI 46 +/- 6 kg/m(2)), undergoing laparoscopic gastric bypass surgery. Biopsies were taken as paired samples [subcutaneous and visceral adipose tissue (AT)] at the beginning of the surgical process at 11:00 h in the morning. Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were also studied. The expression of clock genes (PER2, BMAL1, and CRY1) was measured by quantitative real-time PCR, Western blot, and immunohistochemical analysis. RESULTS: Gene expression was significantly higher in women than in men for the three genes studied in both ATs (P < 0.05). In visceral fat, these differences were more marked. (P < 0.001). Western blot analysis partially confirmed these results since statistical differences were observed for PER2 in both ATs and for CRY1 in subcutaneous adipose tissue. There were no differences in BMAL1 protein expression. Interestingly, clock gene expression level was correlated with LDL-C and HDL-C (P < 0.05). Moreover, we found significant associations with body fat mass in women and with age in men. CONCLUSIONS: Clock genes expression is sex dependent in human adipose tissue from morbidly obese subjects and correlates to a decreased in metabolic syndrome-related traits. These preliminary results make necessary to go deep into the knowledge of the molecular basis of the sexual dimorphism in chronobiology. PMID- 22081239 TI - Learning curve of thoracic pedicle screw placement using the free-hand technique in scoliosis: how many screws needed for an apprentice? AB - PURPOSE: The purpose of this study is to evaluate the learning curve of thoracic pedicle screw (TPS) placement of an inexperienced apprentice in scoliosis with the free-hand technique. METHODS: The patients with scoliosis who underwent TPS inserted with the free-hand technique by the apprentice under the direction of a chief surgeon were included in this study. The TPS placement by the apprentice was evaluated by examining the assessed position in chronological subgroups of 30 screws. The TPS position was assessed on the postoperative computed tomography (CT) scan images using Zdichavsky grading evaluation system and pedicle breach. The rates of good and dangerous screw placement and the rates of pedicle breaches in each apprentice subgroup were compared with those in the chief surgeon group. RESULTS: Thirty-eight patients with 311 TPS were retrospectively analyzed in our study. Of all screws, 154 pedicle screws were inserted by the apprentice, and were divided chronologically into five subgroups. The rates of dangerous placement performed by the apprentice in the first two subgroups were 26.7 and 23.3%, respectively, and were significantly higher than 9.1% by the chief surgeon (P < 0.05). Meanwhile, the breach rate was 46.6% in subgroup 1 and 50.0% in subgroup 2, and was significantly higher than 29.3% in chief surgeon (P < 0.05). Furthermore, after the first 60 TPS placements, the assessed rates in apprentice reached to a stable level, and no significant difference could be found among the subgroups (subgroup 3, 4 and 5) and the chief surgeon group (P > 0.05). CONCLUSIONS: For an apprentice, an experience of at least 60 screw placements under the direction of an experienced surgeon is needed for inserting the TPS in scoliosis using the free-hand technique independently. PMID- 22081240 TI - Appendix stump closure with titanium clips in laparoscopic appendectomy. AB - PURPOSE: Different techniques, including clips, have been used to close the stump in laparoscopic appendectomy. The aim was to investigate the results after application of a newly developed titanium clip for this operation. METHODS: From June 2008 to February 2010, 104 patients from two different hospitals undergoing laparoscopic appendectomy were included in this prospective study. Closure of the appendix base was generally intended with a titanium double-shanked clip (DS Clip). The variables of interest were intra-and postoperative complications, operation time and hospital stay. Furthermore, an evaluation of the clip's practicability by the surgeon was performed using a standardised questionnaire. RESULTS: In 104 patients screened intraoperatively, four patients had to be excluded as the operating surgeon felt that the clip was not adequate for closing the stump, generally because of severe inflammation of the base of the appendix with involvement of the caecum. One patient developed an intra-abdominal abscess which had to be drained interventionally; no reoperations were necessary. The overall complication rate, the operation time and the hospital stay were well comparable with other devices for appendix stump closure such as staplers, loops or polymeric clips. The practicability of the clip was mainly rated as excellent or good by the operating surgeons. CONCLUSION: This study suggests that the presented titanium DS-Clip is a safe and cost-effective technique for securing the appendix base in laparoscopic appendectomy. The application is easy and can be learned quickly, making it a good option also for teaching hospitals. PMID- 22081241 TI - Preadolescents' and parents' dietary coping efficacy during behavioral family based weight control treatment. AB - Developmentally relevant high-risk dietary situations (e.g., parties where tempting foods are available) may influence overweight youth's weight control, as they increase risk for overeating. Better self-efficacy for coping with these situations-which preadolescents may learn from their parents-could foster successful weight control. Overweight preadolescents (N = 204) ages 7-12 years (67% female), each with one parent, separately completed the Hypothetical High Risk Situation Inventory (HHRSI) pre- and post-weight loss treatment. The HHRSI assesses temptation to overeat and confidence in refraining from overeating in response to four high-risk dietary scenarios. Participants generated coping strategies for each scenario. Coping strategies and confidence increased and temptation decreased from pre- to post-weight loss treatment. Parents' increase in confidence from pre- to post-treatment was associated with preadolescents' and parents' weight loss. Tailoring treatments to enhance parents' coping skills (e.g., building strategies, targeting high temptation/low confidence scenarios) may maximize preadolescents' weight control. PMID- 22081242 TI - Reply to "how to diagnose Mycoplasma pneumoniae etiology in a child with pneumonia". PMID- 22081243 TI - The process of identifying, solving and preventing drug related problems in the LIMM-study. AB - OBJECTIVE: To avoid negative effects of drug treatment and need for additional medical care, drug treatment must be individualised. Our research group has developed a model for clinical pharmacy which improves several aspects of the patient's drug treatment. This study describes the process behind these improvements, i.e. drug related problems identified by pharmacists within a clinical pharmacy service. SETTING: Three wards at a department of internal medicine. METHOD: Pharmacists performed systematic interventions during the patient's hospital stay, aiming to identify, solve and prevent drug related problems in the elderly. Identified drug related problems were put forward to the health care team and discussed. Information on identified problems, and their outcomes was collected and analysed. A questionnaire was used to evaluate the health care personnel's attitudes towards the process. MAIN OUTCOME MEASURE: The number of drug related problems identified by the clinical pharmacists, the proportion of problems discussed with the physicians, the proportion of problems adjusted by the physicians and whether pharmacists and physicians prioritised any subgroup of drug related problems when choosing which problems to address. Finally, we wanted to evaluate the health care personnel's attitudes towards the model. RESULTS: In total, 1,227 problem were identified in 190 patients. The pharmacists discussed 685 (55.8%) of the identified problems with the physicians who accepted 438 (63.9%) of the suggestions. There was no significant difference in which subgroup to put forward and which to adjust. There was a high response rate (84%) to the questionnaire, and the health care personnel estimated the benefits to be very high, both for the patients and for themselves. CONCLUSION: The process for identifying, solving and preventing drug related problems was good and the different types of problems were considered equally important. The addition of a clinical pharmacy service was considered very useful. This suggests that the addition of our clinical pharmacy service to the hospital setting add skills of great importance. PMID- 22081244 TI - The prevalence of chromosomal abnormalities in subgroups of infertile men. AB - BACKGROUND: The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of chromosomal abnormalities, possibly by using parameters other than sperm concentration. The aim of this study was to evaluate several clinical parameters in azoospermic and non-azoospermic men, in order to assess the prevalence of chromosomal abnormalities in different subgroups of infertile men. METHODS: In a retrospective cohort of 1223 azoospermic men and men eligible for ICSI treatment, we studied sperm parameters, hormone levels and medical history for an association with chromosomal abnormalities. RESULTS: The prevalence of chromosomal abnormalities in the cohort was 3.1%. No association was found between chromosomal abnormalities and sperm volume, concentration, progressive motility or total motile sperm count. Azoospermia was significantly associated with the presence of a chromosomal abnormality [15.2%, odds ratio (OR) 7.70, P < 0.001]. High gonadotrophin levels were also associated with an increased prevalence of chromosomal abnormalities (OR 2.96, P = 0.013). Azoospermic men with a positive andrologic history had a lower prevalence of chromosomal abnormalities than azoospermic men with an uneventful history (OR 0.28, P = 0.047). In non-azoospermic men, we found that none of the studied variables were associated with the prevalence of chromosomal abnormalities. CONCLUSIONS: We show that the highest prevalence of chromosomal abnormalities is found in hypergonadotrophic azoospermic men with an uneventful andrologic history. PMID- 22081245 TI - Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro. AB - BACKGROUND: Breast cancer development involves a series of mutations in a heterogeneous group of proto-oncogenes/tumor suppressor genes that alter mammary cells to create a microenvironment permissive to tumorigenesis. Exposure to hormones during infertility treatment may have a mutagenic effect on normal mammary epithelial cells, high-risk breast lesions and early-stage breast cancers. Our goal was to understand the association between infertility treatment and normal and cancerous breast cell proliferation. METHODS: MCF-10A normal mammary cells and the breast cancer cell lines MCF-7 [estrogen receptor (ER) positive, well differentiated] and HCC 1937 (ER-negative, aggressive, BRCA1 mutation) were treated with the weak ER activator clomiphene citrate and hormones that are increased during infertility treatment. Direct effects of treatment on cell proliferation and colony growth were determined. RESULTS: While clomiphene citrate had no effect on MCF-10A cells or MCF-7 breast cancer cells, it decreased proliferation of HCC 1937 versus untreated cells (P= 0.003). Estrogen had no effect on either MCF-10A or HCC 1937 cells but, as expected, increased cell proliferation (20-100 nM; P<=0.002) and colony growth (10-30 nM; P< 0.0001) of MCF-7 cells versus control. Conversely, progesterone decreased both proliferation (P= 0.001) and colony growth (P= 0.01) of MCF-10A cells, inhibited colony size of MCF-7 cells (P= 0.01) and decreased proliferation of HCC 1937 cells (P= 0.008) versus control. hCG (100 mIU/ml) decreased both proliferation (P <= 0.01) and colony growth (P <= 0.002) of all three cell lines. CONCLUSIONS: Although these data are preclinical, they support possible indirect estrogenic effects of infertility regimens on ER-positive breast cancer cells and validate the potential protective effect of pregnancy-related exposure to hCG. PMID- 22081246 TI - Impact of 'LH activity' supplementation on serum progesterone levels during controlled ovarian stimulation: a systematic review. AB - BACKGROUND: The influence of LH on serum progesterone rise during gonadotrophin stimulation is a matter of debate. The purpose of this analysis was to assess the impact of supplementation with 'LH activity' products on serum progesterone changes before hCG administration in GnRH analog-treated women. METHODS: A computerized literature search was performed to identify studies comparing FSH treatment alone to those that provided supplementation with 'LH activity' using hMG, recombinant (r)LH (rLH) or hCG in GnRH analog protocols. Data regarding stimulation regimens were extracted from those that reported serum progesterone levels at the time of hCG in order to assess the specific role of LH activity products. RESULTS: Serum progesterone determination at the time of hCG administration was performed in 34 out of 108 studies comparing the effects of FSH alone or in combination with LH activity products. In a vast majority, no significant difference in serum progesterone could be found between stimulation regimens. However, in four studies where LH activity (three hMG and one rLH) was administered from the beginning of ovarian stimulation, serum P-values were significantly decreased. In contrast, in two studies where LH activity (hCG) was provided during the late follicular phase, serum P-values were significantly increased. Analysis of confounding factors showed that the intensity of ovarian stimulation is the most important determining factor to explain serum progesterone elevation at the time of hCG administration, CONCLUSIONS: This systematic review shows that providing LH activity supplementation in combination with FSH during ovarian stimulation does not have a consistent effect on serum progesterone concentrations at the time of hCG administration. However, these data also suggest that, in accordance with physiological concept, the timing of LH activity administration could influence the impact on serum progesterone changes. PMID- 22081247 TI - Family-based analysis of susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder. A previous genome-wide association study (GWAS) identified five single nucleotide polymorphisms (SNPs) which were independently associated with PCOS in Han Chinese. To overcome population stratification, a family-based analysis was conducted to validate whether these five SNPs are associated with PCOS. METHODS: A total of 276 family trios (828 participants) having a proband with PCOS were included in the family-based study. The transmission disequilibrium test (TDT) was used to analyze the association between PCOS and five SNPs rs13429458, rs12478601, rs13405728, rs10818854 and rs2479106 in three susceptible loci 2p16.3, 2p21 and 9q33.3. RESULTS: A positive association was observed for the SNP rs13429458 (P= 3.74 * 10(-5)). CONCLUSIONS: TDT confirms that SNP rs13429458, in the THADA gene, is significantly associated with risk of PCOS. This family-based analysis enhances our previous case-control GWAS and provides further support for the role of susceptibility loci in PCOS. PMID- 22081248 TI - Development of clinical priority access criteria for assisted reproduction and its evaluation on 1386 infertile couples in New Zealand. AB - BACKGROUND: In New Zealand ranking patients for elective, publicly funded procedures uses clinical priority access criteria (CPAC). A CPAC to prioritize patients seeking assisted reproductive technology (ART) was developed in 1997 and implemented nationwide in 2000. This study describes the development of the ART CPAC tool and its evaluation on 1386 couples referred to a single tertiary service from 1998 to 2005. METHODS: A total of 48 health professionals and consumers assisted in criteria development. A score between 0 and 100 points was calculated for each couple and those who reached >=65 points were eligible for publicly funded ART. Couples beneath the treatment threshold were placed on active review; the review being the date the score was calculated to reach the treatment threshold. Couples who would never be eligible or who were on active review were offered private treatment. Treatments and outcomes (spontaneous and treatment dependent live birth pregnancies) were used to evaluate the criteria. RESULTS: Three social criteria (duration infertility, number of children and sterilization status) and two objective criteria (diagnosis and female age) formed the priority score. Of the evaluated couples, 643 (46%) were eligible within 1 year of referral (Group 1), 451 (33%) >1-5 years from referral (Group 2) and 292 (21%) couples were never eligible (Group 3). The predominant ART was IVF. A total of 480 couples had at least one IVF treatment with 404 (84%) having publicly funded treatment. A total of 762 (55%) women gave birth, 473 from treatment and 289 spontaneously. Group 1 had more pregnancies from treatment while Group 2 had most pregnancies overall being mainly from spontaneous pregnancies. Compared with Group 3 cases the hazard ratio using time to spontaneous live birth pregnancy for Group 1 couples was significantly lower, 0.51 (95% confidence interval 0.36-0.74) and for Group 2 cases significantly higher, 1.86, (1.35-2.58). Treatments using ART were evaluated for the three eligibility groups, with the never eligible divided into women age <40 (Group 3a) and woman age >=40 at referral (Group 3b). Compared with Group 1 cases the hazard ratio to treatment dependent live birth pregnancy was similar for Groups 2 and 3a but significantly lower for Group 3b (0.37, 0.14-0.90). CONCLUSIONS: The clinical priority access score was able to discriminate between the chance of pregnancy with and without treatment and those offered and not offered treatment. The CPAC is a useful model for informing the allocation of public funding for ART in other countries. PMID- 22081249 TI - Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage. AB - BACKGROUND: Angiogenesis is a key feature of endometrial development. Inappropriate endometrial vascular development has been associated with recurrent miscarriage (RM) with increased amounts of perivascular smooth muscle cells surrounding them. METHODS: In the current study, we have used immunohistochemistry to study temporal and spatial expression of a series of angiogenic growth factors (AGFs) and their receptors; vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2, VEGF-R3, platelet-derived growth factor (PDGF)-BB, PDGF-Ralpha, PDGF-Rbeta, transforming growth factor (TGF)-beta1, TGF-betaRI, TGF-betaRII, angiopoietin (Ang)-1, Ang-2 and Tie-2, in the proliferative, early secretory and mid-late secretory phase endometrium from control women as well as in the mid-late secretory phase of women with a history of RM. The AGFs and their receptors studied were immunostained and assessed separately in stromal, vascular smooth muscle, endothelial and glandular epithelial cells. Laser capture microdissection and real-time RT-PCR were used to confirm expression patterns observed by immunohistochemistry. RESULTS: Most AGFs investigated showed both temporal and spatial expression patterns in normal cycling endometrium. In addition, immunostaining intensity for several AGFs was altered in women with a history of RM, particularly in vascular smooth muscle cells (VSMCs). VSMC expression of TGF-beta1, VEGF-R1 and VEGF-R2 was increased while expression of PDGF-BB, TGF-betaRI, TGF-betaRII, Ang-2, VEGF-A and VEGF-C was reduced. CONCLUSIONS: This study confirms that the cycling endometrium is a highly angiogenic tissue and that this process is likely to be altered in women with a history of RM and may contribute to the aetiology of this condition. PMID- 22081250 TI - CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis. AB - BACKGROUND: Numerous studies have reported CFTR mutations in CBAVD (congenital bilateral absence of the vas deferens) patients, but their results are not completely consistent. Here, we present a systemic review and meta-analysis with emphasis on clarifying further the genetic association of CFTR mutations with CBAVD. METHODS: We searched the MEDLINE database until March, 2011 for eligible articles reporting CFTR mutations in CBAVD. Relevant data from each included study were abstracted by two independent reviewers. The overall frequency of CFTR mutations in CBAVD and the odds ratio (OR) for common specific alleles were pooled under random-effect or fixed-effect model as appropriate. Subgroup analysis was performed by ethnicity, and potential heterogeneity and bias were both assessed. RESULTS: Among CBAVD patients, 78% had at least one CFTR mutation, 46% having two and 28% only one. Moreover, the common heterozygous F508del/5T and F508del/R117H were observed in 17 and 4% of CBAVD cases respectively, and the allele frequency in CBAVD was 17% for F508del, 25% for 5T and 3% for R117H. Subgroup analysis indicated an increased frequency of cases with two mutations in Caucasian patients than in Non-Caucasian (68 versus 50%, P= 0.012), but no differences for cases with at least one mutation (88 versus 77%, P= 0.163) or with only one mutation (17 versus 25%, P= 0.115). Caucasian patients had higher F508del frequency, but lower 5T frequency, than Non-Caucasian (22 versus 8%, P= 0.001; 20 versus 31%, P= 0.009). Summary OR was 9.25 for 5T [95% confidence interval (CI) 7.07-12.11, P= 0.000], with moderate heterogeneity (I(2)= 49.20%, P= 0.019) and evident bias (Egger's test, P= 0.005), and it was 19.43 for 5T/(TG)12_13 (95% CI 10.48-30.03, P= 0.000) without any evidence of heterogeneity (I(2)= 0.1%, P= 0.391) and bias (Egger's test, P= 0.160). The OR for 5T/(TG)12_13 was significantly higher than that for 5T allele (P= 0.000). CONCLUSIONS: In summary, our results demonstrate a high frequency of CFTR mutations in CBAVD patients, and these exhibit evident ethnic differences. In addition, 5T allele and 5T/(TG)12_13 may contribute to the increased risk for CBAVD, with the 5T penetrance probably being modulated by adjacent (TG)12_13. PMID- 22081251 TI - Human embryonic development after blastomere removal: a time-lapse analysis. AB - BACKGROUND: Blastomere biopsy of human embryos is performed for preimplantation genetic diagnosis (PGD). The impact on further development is largely unexplored, though studies on mice suggest an influence on the hatching process. The objective of this study was to evaluate the effect of blastomere biopsy on early human embryonic development using time-lapse analysis. METHODS: Embryos from couples undergoing PGD treatment or IVF/ICSI were included. In the PGD group, 56 human embryos had one blastomere biopsied. As controls, 53 non-biopsied IVF/ICSI embryos were selected. All embryos were cultured until 5 days after fertilization in a time-lapse incubator (EmbryoScopeTM). Images of embryos were acquired every 20 min. Time-points of key embryonic events were registered, and development in the two groups was compared. RESULTS: Duration of the biopsied cell-stage in the PGD group was longer than in the control group (P < 0.001), causing biopsied embryos to reach subsequent embryonic stages until hatching at significantly later time-points (P(compaction) < 0.001; P(morula) < 0.001; P(earlyblast) < 0.001; P(fullblast) = 0.01), but with unchanged intervals. Embryos in the PGD group started hatching at the same time-point as the control group, but had a smaller diameter (P < 0.001), and a thicker zona pellucida (P < 0.001) when hatching. Time-lapse videos revealed that in the control group, expansion of the blastocyst caused continuous thinning of zona pellucida until the blastocyst hatched, whereas in the PGD group the blastocyst hatched through the opening in zona pellucida artificially introduced prior to the biopsy. CONCLUSIONS: We find that blastomere biopsy prolongs the biopsied cell-stage, possibly caused by a delayed compaction and alters the mechanism of hatching. PMID- 22081252 TI - Advanced renal mass imaging: diffusion and perfusion MRI. AB - Computed tomography (CT) is considered the imaging modality of choice in evaluation of renal lesions. The advantages of magnetic resonance imaging (MRI) compared to CT include superior soft tissue contrast, avoidance of ionizing radiation and iodinated contrast media, and the possibility of performing functional and advanced imaging techniques such as diffusion-weighted (DWI) and perfusion-weighted imaging (PWI). Although the traditional role of MRI in the evaluation of renal mass is primarily that of a problem-solving tool, DWI and PWI are expanding the role of MRI in management of renal cell cancers. DWI and PWI have shown considerable promise not only in renal lesion detection and characterization as benign or malignant, but also in assessment of renal cell cancer subtype and nuclear grade. Furthermore, these techniques have the potential to assist with tailoring patient- and disease-specific management by providing surgical planning in patients with localized renal cell cancer and assessing treatment response in patients with advanced renal cell cancer undergoing targeted chemotherapy. PMID- 22081253 TI - Techniques of biliary reconstruction following bile duct resection (with video). AB - In several clinical situations, including resection of malignant or benign biliary lesions, reconstruction of the biliary system using the Roux-en-Y jejunum limb has been adopted as the standard procedure. The basic technique and the procedural knowledge essential for most gastroenterological surgeons are described in this article, along with a video supplement. Low complication rates involving anastomotic insufficiency or stricture can be achieved by using proper surgical techniques, even following small bile duct reconstruction. Using the ropeway method to stabilize the bile duct and jejunal limb allows precise mucosa to-mucosa anastomosis with interrupted sutures of the posterior row of the anastomosis. Placement of a transanastomotic stent tube is the second step. The final step involves suturing the anterior row of the anastomosis. In contrast to the lower extrahepatic bile duct, the wall of the hilar or intrahepatic bile duct can be recognized within the fibrous connective tissue in the Glissonean pedicle. The portal side of the duct should be selected for the posterior wall during anastomosis owing to its thickness. Meticulous inspection to avoid overlooking small bile ducts could decrease the chance of postoperative intractable bile leakage. In reconstruction of small or fragile branches, a transanastomotic stent tube could work as an anchor for the anastomosis. PMID- 22081254 TI - Identification of novel hybrids between Cryptococcus neoformans var. grubii VNI and Cryptococcus gattii VGII. AB - Cryptococcus neoformans and Cryptococcus gattii are pathogenic yeasts causing meningoencephalitis in immunocompromised and immunocompetent hosts. The fungus is typically haploid, and sexual reproduction occurs normally between individuals with opposite mating types, alpha and a. C. neoformans var. grubii (serotype A) is comprised of molecular types VNI, VNII, and VNB, and C. neoformans var. neoformans (serotype D) contains the molecular type VNIV. Additionally, diploid or aneuploid AD hybrids (VNIII) have been reported. C. gattii contains the molecular types VGI, VGII, VGIII, and VGIV, which encompass both serotypes B and C. To identify possible hybrid strains, URA5-RFLP analysis was performed on 350 globally obtained clinical, environmental, and veterinary isolates. Four clinical isolates from cerebrospinal fluid showed combination patterns of C. neoformans var. grubii and C. gattii: Brazil (n = 2), Colombia (n = 1), and India (n = 1). These strains were monokaryotic and diploid or aneuploid. M13 PCR fingerprinting showed that they contained fragments of both proposed parental groups. Luminex IGS genotyping identified these isolates as hybrids with two different molecular type combinations: three VNI/VGII and one VNI/VGI. Blue color development on CGB agar was delayed in three isolates and absent in one. C. gattii-specific PCR confirmed the presence of C. gattii in the hybrids. CAP59 allele-specific PCR revealed that all the hybrids contained both serotype A and B alleles. Determination of mating-type allelic patterns by PCR revealed that the isolates were alphaA aB. This is the first study discovering novel natural hybrids between C. neoformans molecular type VNI and C. gattii molecular type VGII. PMID- 22081255 TI - Paracoccidioidal infection in HIV patients at an endemic area of paracoccidioidomycosis in Brazil. AB - The association between paracoccidioidomycosis (PCM) and AIDS is relatively rare in contrast to the higher incidence of other systemic mycosis. The explanation may be that AIDS is still predominantly an urban disease, and the PCM is endemic in Latin American rural areas. The aim of this study was to detect the prevalence of Paracoccidioides brasiliensis infection in HIV-positive patients at an endemic area of paracoccidioidomycosis in Brazil. Skin test with purified 43 kD glycoprotein (gp43) was performed in 90 HIV/AIDS patients. The prevalence found was 12.2% and it may be even greater, considering that HIV/AIDS patients may not respond to the intradermal test, which depends on cellular immunity for its positivity. PMID- 22081256 TI - Clopidogrel tapering as a strategy to attenuate platelet rebound phenomenon in patients with bare-metal stents. AB - Early clustering of adverse cardiovascular events after abrupt cessation of clopidogrel has been reported in patients with acute coronary syndromes. A platelet rebound phenomenon may contribute to this increased thrombotic risk and a gradual drug tapering may attenuate this proposed platelet effect. Accordingly, we aimed to assess the effect of clopidogrel tapering on platelet reactivity. Twenty patients who underwent elective percutaneous coronary interventions with bare metal stents receiving 3 months of clopidogrel therapy (75 mg daily) were randomized to either of two discontinuation strategies: (1) Off group-abrupt drug cessation or (2) Tapering group-receiving clopidogrel 75 mg every other day for 4 weeks duration. Light transmission aggregometry, induced by ADP (5 and 10 MUM) and collagen, was measured at four time-points (at baseline and 2, 4 and 6 weeks after randomization). In the off group, there was an early rise in platelet reactivity at 2 weeks after abrupt drug cessation compared to baseline, as measured by ADP 5 MUmol/l (39.6 +/- 2.8 vs. 67.9 +/- 6.0, P < 0.001). The tapering regimen suppressed this rebound platelet aggregation by ADP 5 MUmol/l at 2 weeks (P = 0.001) and 4 weeks (P = 0.001). Similar results were found with ADP 10 MUmol/l and collagen agonists. Abrupt cessation of clopidogrel results in an early rise in platelet aggregability in patients with BMS that is attenuated by a tapering regimen. Clopidogrel administration every other day may achieve similar levels of platelet inhibition as full dose therapy. Further investigations evaluating clopidogrel tapering strategies and their potential clinical impact are warranted. PMID- 22081257 TI - Growth hormone treatment in adults with Prader-Willi syndrome: the Scandinavian study. AB - Prader-Willi syndrome (PWS) is characterized by short stature, muscular hypotonia, cognitive dysfunction, and hyperphagia usually leading to severe obesity. Patients with PWS share similarities with growth hormone deficiency (GHD). Few studies have dealt with growth hormone (GH) treatment in PWS adults. The purpose of the Scandinavian study was to evaluate the effects of GH on body composition, lipid and glucose metabolism, physical performance and safety parameters in adults with PWS. Twenty-five women and 21 men with PWS were randomized to treatment with GH or placebo during 1 year followed by 2 years of open labeled GH treatment. At baseline 1/3 had normal BMI, six patients severe GHD, ten impaired glucose tolerance and seven diabetes. At 1 year insulin-like growth factor I (IGF-I) SDS had increased by 1.51 (P < 0.001) and body composition improved in the GH treated group. Visceral fat decreased by 22.9 ml (P = 0.004), abdominal subcutaneous fat by 70.9 ml (P = 0.003) and thigh fat by 21.3 ml (P = 0.013), whereas thigh muscle increased 6.0 ml (P = 0.005). Lean body mass increased 2.25 kg (P = 0.005), and total fat mass decreased 4.20 kg (P < 0.001). The positive effects on body composition were maintained after 2 years of GH treatment. Peak expiratory flow increased by 12% (P < 0.001) at 2 years of GH treatment. Lipid and glucose metabolism were unchanged, however, three patients developed diabetes at 2 years of GH treatment. In conclusion GH treatment had beneficial effects on the abnormal body composition without serious adverse events making it a logic treatment option in adults with PWS. PMID- 22081258 TI - A comprehensive, computer-model-based approach for diagnosis and treatment of complex acid-base disorders in critically-ill patients. AB - We have developed a computer-model-based approach to quantitatively diagnose the causes of metabolic acid-base disorders in critically-ill patients. We use an interstitial-plasma-erythrocyte (IPE) model that is sufficiently detailed to accurately calculate steady-state changes from normal in fluid volumes and electrolyte concentrations in a given patient due to a number of causes of acid base disorders. Normal fluid volumes for each patient are determined from their sex, height and weight using regression equations derived from measured data in humans. The model inputs (electrolyte masses and volumes) are altered to simulate the laboratory chemistry of each critically-ill patient. In this process, the model calculates changes in body-fluid volumes, osmolality and yields the individual values of IPE base excess (BE(IPE)) attributed to changes due to: (1) fluid dilution/contraction, (2) gain or loss of Cl(-), (3) hyper- or hypoalbuminemia, (4) presence of unmeasured ions, (5) gain of lactate, (6) gain or loss of phosphate, (7) gain or loss of calcium and magnesium, (8) gain or loss of potassium and (9) gain or loss of sodium. We use critically-ill patient data to show how our new approach is more informative and much simpler to interpret as compared to the approaches of Siggaard-Andersen or Stewart. We demonstrate how the model can be used at the bedside to diagnose acid-base disorders and suggest appropriate treatment. Hence, this new approach gives clinicians a new tool for diagnosing disorders and specifying fluid-therapy options for critically-ill patients. PMID- 22081259 TI - Capability of a new paediatric oesophageal Doppler monitor to detect changes in cardiac output during testing of external pacemakers after cardiac surgery. AB - BACKGROUND: The Cardio QPTM oesophageal Doppler monitor measures the velocity time integral of the blood flow in the descending aorta. Based on system integrated normograms of the aortic cross-sectional area of a paediatric population, the cardiac output is calculated and displayed. OBJECTIVE: Evaluation of the capability of the Cardio QPTM to detect changes in cardiac output during desynchronizing ventricular pacing (VVI) in children after cardiac surgery. PATIENTS: Eleven children (6 female, 5 male) with epicardial pacemaker electrodes admitted to the paediatric intensive care unit (PICU) after corrective surgery for congenital heart defects. Mean age: 6.3 (2.1-15.0) months, mean body weight: 5.3 (3.5-7.8) kg. INTERVENTIONS: After baseline measurements of cardiac output (base I), we performed 3 steps, each lasting 5 min: (1) ventricular pacing (VVI), (2) baseline (base II) recording, (3) atrial pacing (AOO). We measured the effects on haemodynamic parameters and blood gases as well as on the measured cardiac output. RESULTS: Ventricular pacing, with atrio-ventricular dyssynchrony, led to a significant drop in blood pressure and central venous saturation. Cardiac output parameters showed a decrease in stroke volume (SV) from 4.9+/-2.2 to 4.2+/-2.1 ml (P = 0.005) and cardiac index (CI) (2.6+/-1.1-2.1+/-0.8 ml/min/m(2)) (P = 0.009) during ventricular pacing. Cardiac index and haemodynamic parameters during atrial stimulation did not show significant changes from baseline. CONCLUSION: The Cardio QPTM seems to be capable of detecting slight changes in cardiac output. PMID- 22081260 TI - Whether ideal free or not, predatory mites distribute so as to maximize reproduction. AB - Ideal free distribution (IFD) models predict that animals distribute themselves such that no individual can increase its fitness by moving to another patch. Many empirical tests assume that the interference among animals is independent of density and do not quantify the effects of density on fitness traits. Using two species of predatory mites, we measured oviposition as a function of conspecific density. Subsequently, we used these functions to calculate expected distributions on two connected patches. We performed an experimental test of the distributions of mites on two such connected patches, among which one had a food accessibility rate that was twice as high as on the other. For one of the two species, Iphiseius degenerans, the distribution matched the expected distribution. The distribution also coincided with the ratio of food accessibility. The other species, Neoseiulus cucumeris, distributed itself differently than expected. However, the oviposition rates of both species did not differ significantly from the expected oviposition rates based on experiments on single patches. This suggests that the oviposition rate of N. cucumeris was not negatively affected by the observed distribution, despite the fact that N. cucumeris did not match the predicted distributions. Thus, the distribution of one mite species, I. degenerans, was in agreement with IFD theory, whereas for the other mite species, N. cucumeris, unknown factors may have influenced the distribution of the mites. We conclude that density-dependent fitness traits provide essential information for explaining animal distributions. PMID- 22081261 TI - Phenotypic plasticity facilitates resistance to climate change in a highly variable environment. AB - Increased summer drought will exacerbate the regeneration of many tree species at their lower latitudinal and altitudinal distribution limits. In vulnerable habitats, introduction of more drought-tolerant provenances or species is currently considered to accelerate tree species migration and facilitate forest persistence. Trade-offs between drought adaptation and growth plasticity might, however, limit the effectiveness of assisted migration, especially if introductions focus on provenances or species from different climatic regions. We tested in a common garden experiment the performance of Pinus sylvestris seedlings from the continental Central Alps under increased temperatures and extended spring and/or summer drought, and compared seedling emergence, survival and biomass allocation to that of P. sylvestris and closely related Pinus nigra from a Mediterranean seed source. Soil heating had only minor effects on seedling performance but high spring precipitation doubled the number of continental P. sylvestris seedlings present after the summer drought. At the same time, twice as many seedlings of the Mediterranean than the continental P. sylvestris provenance were present, which was due to both higher emergence and lower mortality under dry conditions. Both P. sylvestris provenances allocated similar amounts of biomass to roots when grown under low summer precipitation. Mediterranean seedlings, however, revealed lower phenotypic plasticity than continental seedlings under high precipitation, which might limit their competitive ability in continental Alpine forests in non-drought years. By contrast, high variability in the response of individual seedlings to summer drought indicates the potential of continental P. sylvestris provenances to adapt to changing environmental conditions. PMID- 22081262 TI - Determination of new prediction formula for nasal continuous positive airway pressure in Turkish patients with obstructive sleep apnea syndrome. AB - BACKGROUND: Race/ethnicity may play an important role in determining body size, severity of obstructive sleep apnea syndrome (OSAS), and effective continuous positive airway pressure (CPAP) (Peff). Turkey is composed of different ethnic groups. Therefore, the aims of this study were to determine new prediction formula for CPAP (Ppred) in Turkish OSAS patients, validate performance of this formula, and compare with Caucasian and Asian formulas. METHODS: Peff of 250 newly diagnosed moderate-to-severe OSAS patients were calculated by in-laboratory manual titration. Correlation and multiple linear regression analysis were used to model effects of ten anthropometric and polysomnographic variables such as neck circumference (NC) and oxygen desaturation index (ODI) on Peff. New formula was validated in different 130 OSAS patients and compared with previous formulas. RESULTS: The final prediction formula was [Formula: see text]. When Peff of control group was assessed, it was observed that mean Peff was 8.39 +/- 2.00 cmH(2)O and Ppred was 8.23 +/- 1.22 cmH(2)O. Ppred was within +/-3 cmH(2)O of Peff in 96.2% patients. Besides, Peff was significantly correlated with new formula, and prediction formulas developed for Caucasian and Asian populations (r = 0.651, p < 0.001, r = 0.648, p < 0.001, and r = 0.622, p < 0.001, respectively). CONCLUSIONS: It is shown that level of CPAP can be successfully predicted from our prediction formula, using NC and ODI and validated in Turkish OSAS patients. New equation correlates with other formulas developed for Caucasian and Asian populations. Our simple formula including ODI, marker of intermittent hypoxia, may be used easily in different populations. PMID- 22081264 TI - Automatic subarachnoid space segmentation and hemorrhage detection in clinical head CT scans. AB - PURPOSE: The subarachnoid space (SAS) lies between the arachnoid membrane and the pia mater of the human brain, normally filled with cerebrospinal fluid (CSF). Subarachnoid hemorrhage (SAH) is a serious complication of neurological disease that can have high mortality and high risk of disability. Computed tomography (CT) head scans are often used for diagnosing SAH which may be difficult when the hemorrhage is small or subtle. A computer-aided diagnosis system from CT images is thus developed to augment image interpretation. METHODS: Supervised learning using the probability of distance features of several landmarks was employed to recognize SAS. For each CT image, the SAS was approximated in four steps: (1) Landmarks including brain boundary, midsagittal plane (MSP), anterior and posterior intersection points of brain boundary with the MSP, and superior point of the brain were extracted. (2) Distances to all the landmarks were calculated for every pixel in the CT image, and combined to construct a high-dimensional feature vector. (3) Using head CT images with manually delineated SAS as training dataset, the prior probabilities of distances for pixels within SAS and non-SAS were computed. (4) Any pixel of a head CT scan in the testing dataset was classified as an SAS or non-SAS pixel in a Bayesian decision framework based on its distance features. RESULTS: The proposed method was validated on clinical head CT images by comparison with manual segmentation. The results showed that the automated method is consistent with the gold standard. Compared with elastic registration based on grayscale information, the proposed method was less affected by grayscale variation between normal controls and patients. Compared with manual delineation, the average spatial overlap, relative overlap, and similarity index were, respectively, 89, 63, and 76% for the automatic SAS approximation of the 69 head CT scans tested. The proposed method was tested for SAH detection and yielded a sensitivity of 100% and a specificity of 92%. CONCLUSION: Automated SAH detection with high sensitivity was shown feasible in a prototype computer-aided diagnosis system. The proposed method may be extended for computer-aided diagnosis of several CSF-related diseases relevant to SAS abnormalities. PMID- 22081263 TI - Transfusion risk in cancer patients with chemotherapy-induced anemia when initiating darbepoetin alfa therapy at a baseline hemoglobin level of <9 g/dL versus 9 to <10 g/dL versus >= 10 g/dL: an exploratory analysis of a phase 3 trial. AB - Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anemia (CIA). Safety concerns have prompted changes to the ESA-product information, which now recommends initiating ESAs at hemoglobin (Hb) levels < 10 g/dL (US) or <= 10 g/dL (EU). The present exploratory analysis of a DA trial examined how baseline-Hb levels at ESA initiation affect transfusion rates, Hb response, and safety outcomes in CIA patients. Data were retrospectively analyzed from a phase 3 trial of CIA patients randomised to 500 mcg DA every 3 weeks (Q3 W) or to 2.25 mcg/kg DA weekly (QW) for 15 weeks. In the current analysis, data were reanalyzed by baseline-Hb categories of <9 g/dL (n = 126), 9 to <10 g/dL (n = 225), and >= 10 g/dL (n = 354). The Q3 W and QW groups were combined. Transfusion rates were highest in the <9 g/dL baseline-Hb group in all time periods examined. The Kaplan-Meier percentage (95% CI) of patients achieving Hb >= 10 g/dL was 68% (59, 78) and 88% (82, 92) in the <9 g/dL and 9 to <10 g/dL baseline-Hb groups, respectively. With lower baseline-Hb, incidence of a >= 1 g/dL-Hb rise in 14 days progressively decreased. Incidence of venous thromboembolic events was similar in all baseline-Hb groups and similar between patients with or without a >= 1 g/dL-Hb rise in 14 days. Overall, transfusion risk increased and Hb response decreased at lower baseline-Hb levels in this exploratory analysis. When following ESA-product information to initiate ESAs at Hb <= 10 g/dL, the greatest benefit may be achieved when initiating close to 10 g/dL. Prospective studies are needed to further examine this hypothesis. PMID- 22081265 TI - Large soft tissue osteochondroma of the heel: a case report and literature review. AB - Soft tissue osteochondromas are the rare tumors of the foot. We present an unusual case of a 30-year-old woman who had a large osteochondroma originating from the soft tissue in the heel region. She made an uneventful recovery following excision. No recurrence was noted at 36 months follow-up. To the best of authors' knowledge, such presentation has not been reported before in the English language-based medical literature. PMID- 22081266 TI - Comment on: Successful treatment of methicillin-resistant Staphylococcus aureus mitral valve endocarditis with sequential linezolid and telavancin monotherapy following daptomycin failure. PMID- 22081267 TI - Comment on: AbaR4 replaces AbaR3 in a carbapenem-resistant Acinetobacter baumannii isolate belonging to global clone 1 from an Australian hospital. PMID- 22081268 TI - Could liposomal amphotericin B (L-AMB) lock solutions be useful to inhibit Candida spp. biofilms on silicone biomaterials? AB - OBJECTIVES: Candida infections associated with catheters remain difficult to manage. Antifungal lock strategies could be a therapeutic option when the device is difficult to remove or in combination with systemic treatment to increase efficacy. This study deals with the antibiofilm potential of liposomal amphotericin B (L-AMB) used as a lock solution to inhibit Candida albicans, Candida glabrata and Candida parapsilosis biofilms in vitro. METHODS: Biofilms aged 12 h and 5 days were formed on silicone catheters. L-AMB (200 or 1000 mg/L) was added to biofilms and catheters were incubated for 4, 12 or 24 h at 37 degrees C. L-AMB was then removed by washing. The metabolic activity of yeasts was assessed by the XTT method up to 48 h after the end of the locks to evaluate the persistence of the antibiofilm activity. Controls without antifungal were used as references to calculate the inhibition percentages induced by L-AMB lock solutions. RESULTS: L-AMB (200 and 1000 mg/L) inhibited, for up to 48 h, C. albicans and C. glabrata biofilms by >70%, regardless of the lock duration. The activity of L-AMB (200 mg/L) against C. parapsilosis mature biofilms was lower and less sustained, especially for 4 h locks. CONCLUSIONS: L-AMB (1000 mg/L) lock solutions strongly inhibited Candida spp. in young and mature biofilms for up to 48 h after the end of the lock. However, overall eradication of the biofilm was not obtained using 1000 mg/L L-AMB as a single lock. These results suggest the usefulness of systemic treatment combined with an L-AMB lock to control Candida spp. biofilms associated with catheters. PMID- 22081269 TI - Motion effects on SUV and lesion volume in 3D and 4D PET scanning. AB - To assess the effect of lesion motion and respiration rate on Standardised Uptake Value (SUV) and the ability of 4D PET to restore any loss in SUV and distortion of lesion volume on two PET/CT systems. A Perspex phantom with four cylindrical reservoirs filled with (18)F-FDG was used in this study. The cylinders measured 5, 10, 15, and 20 mm in diameter. A GE Discovery STE8 (GE Medical Systems Milwaukee, WI) and a Siemens Biograph 64/40 (Siemens Medical Solutions, Erlangen, Germany) scanner was used to acquire a stationary un-gated PET scan of the phantom. Multiple 10 min list mode 4D PET scans were acquired using the Varian RPM on the GE camera and the Anzai Gating system on the Siemens camera. The phantom was scanned at five different respiratory rates and motion amplitudes in a sinusoidal fashion, 15 RPM/1 cm, 15 RPM/2 cm, 15 RPM/4 cm, 30 RPM/2 cm and 7.5 RPM/2 cm (RPM-respirations per minute). Each scan was reconstructed into ten bins and as an un-gated static image. The SUVmax, SUVmean and volume were measured for all four reservoirs using Siemens TrueD analysis software. With increasing lesion movement the SUVmax and SUVmean decreased and the volume increased with the SUVmax in the smallest lesion underestimated by up to a factor of four. The SUVmax, SUVmean and volume were mostly recovered using 4D imaging regardless of amount of lesion displacement. The larger lesions showed better count recovery and volume correction than the smaller lesions. The respiratory rate had no effect of SUV or volume. Un-gated imaging of moving lesions decreases apparent SUV in small lesions significantly and overestimates volumes. 4D PET scanning recovers most of the apparent loss in SUV and distortion of volumes. PMID- 22081270 TI - A novel population balance model to investigate the kinetics of in vitro cell proliferation: part I. Model development. AB - In biotechnology and biomedicine reliable models of cell proliferation kinetics need to capture the relevant phenomena taking place during the mitotic cycle. To this aim, a novel mathematical model helpful to investigate the intrinsic kinetics of in vitro culture of adherent cells up to confluence is proposed in this work. Specifically, the attention is focused on the simulation of proliferation (increase of cell number) and maturation (increase of cell size and DNA content) till contact inhibition eventually takes place inside a Petri dish. Accordingly, the proposed model is based on a population balance (PB) approach that allows one to quantitatively describe cell cycle progression through the different phases the cells of the entire population experienced during their own life. In particular, the proposed model has been developed as a 2D, multi-staged, and unstructured PB, by considering a different sub-population of cells for any single phase of the cell cycle. These sub-populations are discriminated through cellular volume and DNA content, that both increase during the mitotic cycle. The adopted mathematical expressions of the transition rates between two subsequent phases and the temporal increase of cell volume and DNA content are thoroughly analyzed and discussed with respect to those ones available in the literature. Specifically, the corresponding uncertainties and pitfalls are pointed out, by also taking into account the difficulties and the limitations involved in the quantitative measurements currently practicable for these biological systems. A novel mathematical expression for contact inhibition in line with the PB model developed is also formulated, along with a proper comparison between modeled and measurable DNA distributions. The strategy for a reliable, independent tuning of the adjustable parameters involved in the proposed model along with its numerical solution is outlined in Part II of this work, where it is also shown how it can be profitably used to gain a deeper insight into the phenomena involved during cell cultivation under microgravity conditions. PMID- 22081271 TI - Rehabilitation using high-intensity physical training and long-term return-to work in cancer survivors. AB - INTRODUCTION: Due to large and increasing numbers of cancer survivors, long-term cancer-related health issues have become a major focus of attention. This study examined the relation between a high-intensity physical rehabilitation program and return-to-work in cancer survivors who had received chemotherapy. METHODS: The intervention group, consisting of 72 cancer survivors from one hospital (8 men and 64 women, mean age 49 years), followed an 18-weeks rehabilitation program including strength and interval training, and home-based activities. An age matched control group, consisting of 38 cancer survivors (9 men and 29 women), was recruited from two other hospitals. They received only standard medical care. All subjects were evaluated during a telephone interview on employment issues, conducted at +/-3 years after diagnosis. The main outcomes were change in working hours per week and time until return-to-work. RESULTS: Patients in the intervention group showed significant less reduction in working hours per week [ 5.0 h/week vs. -10.8 h/week (P = .03)]. Multivariate analyses showed that the training intervention, the age of patients, and the number of working hours pre diagnosis could explain the improvement in long-term participation at work. Time until (partial) return-to-work was 11.5 weeks for the intervention group versus 13.2 weeks for the control group (P = .40). On long-term follow-up, 78% of the participants from the intervention group versus 66% from the control group had returned to work on the pre-diagnosis level of working hours (P = .18). CONCLUSION: Rehabilitation using high-intensity physical training is useful for working patients to minimize the decreased ability to work resulting from cancer and its treatment. PMID- 22081272 TI - Locked intramedullary femoral nailing without fracture table or image intensifier. AB - The present retrospective study aims to evaluate the outcome in 41 patients of femoral shaft fractures, who had closed intramedullary nailing in lateral decubitus position without fracture table or image intensifier. Mean age was 33.2 (range, 18-70) years. The cannulated reamer in proximal fragment (as intramedullary joystick) and Schanz screw in the distal fragment (as percutaneous joystick) were simultaneously used to assist closed reduction of the fracture without the use of image intensifier. Closed reduction was successful in 38 patients. Open reduction was required in 3 patients. Schanz screw was used for closed reduction in 12 patients. Average number of intra-operative radiographic exposures was 4.4. Two patients had exchange nailing using large diameter nails. One patient had nonunion. Angular and rotatory malalignments were observed in seven patients. We are of the opinion that the present technique is a safe and reliable alternative to achieve closed locked intramedullary nailing and is best suited to stable, less comminuted (Winquist-Hansen types I and II) diaphyseal fractures of the femur. PMID- 22081273 TI - Pituitary immunoexpression of ghrelin in anorexia nervosa. AB - Ghrelin, an orexigenic hormone, is known to occur in the normal anterior pituitary where its physiologic role is uncertain but may include promotion of appetite. We sought to investigate anticipated differences in adenohypophysial and neurohypophysial ghrelin immunoexpression between normal subjects and patients with anorexia nervosa who had succumbed to complications of the disease. We hypothesized that the glands of anorexia nervosa patients would show relative diminished action in ghrelin content. The study included 12 autopsy-derived pituitaries of anorexia nervosa and 10 control glands. The streptavidin-biotin peroxidase complex method and double immunohistochemical staining method were used to determine which cell types expressed both ghrelin and adenohypophysial hormones. Nontumorous control pituitaries were also obtained at autopsy. In anorexia nervosa and control adenohypophyses, ghrelin was mainly localized in somatotrophs and to a lesser extent in corticotrophs and gonadotrophs. Ghrelin accumulated within nerve fibers and Herring bodies in the neurohypophysis and pituitary stalk. In the controls, ghrelin expression was apparent in only a few cases. It was mild and only along few nerve fibers. In the adenohypophyses of anorexia nervosa patients, ghrelin was not depleted. It appears that in these patients, ghrelin is transported in excess from the hypothalamic neurohypophysial tract to the neurohypophysis. PMID- 22081274 TI - Radioactive iodine (131I) therapy for differentiated thyroid cancer in Japan: current issues with historical review and future perspective. AB - Radioactive iodine (RAI, (131)I) has been used as a therapeutic agent for differentiated thyroid cancer (DTC) with over 50 years of history. Recently, it is now attracting attention in medical fields as one of the molecular targeting therapies, which is known as targeted radionuclide therapy. Radioactive iodine therapy (RIT) for DTC, however, is now at stake in Japan, because Japan is confronting several problems, including the recent occurrence of the Great East Japan Disaster (GEJD) in March 2011. RIT for DTC is strictly limited in Japan and requires hospitalization. Because of strict regulations, severe lack of medical facilities for RIT has become one of the most important medical problems, which results in prolonged waiting time for Japanese patients with DTC, including those with distant metastasis, who wish to receive RIT immediately. This situation is also due to various other factors, such as prolonged economic recession, super aging society, and subsequent rapidly changing medical environment. In addition, due to the experience of atomic bombings in Hiroshima and Nagasaki, Japanese people have strong feeling of "radiophobia". There is fear that GEJD and related radiation contamination may worsen this feeling, which might be reflected in more severe regulation of RIT. To overcome these difficulties, it is essential to collect and disclose all information about the circumstances around this therapy in Japan. In this review, we would like to look at this therapy through several lenses, including historical, cultural, medical, and socio-economic points of view. We believe that clarifying the problems is sure to lead to the resolution of this complicated situation. We have also included several recommendations for future improvements. PMID- 22081275 TI - Use of an oral effervescent agent in the evaluation of gastric 67Ga uptake. AB - OBJECTIVE: Gastric uptake of (67)Ga may be observed in patients with no obvious gastric lesions, as well as those with gastric malignancy. The aim of this study was to investigate whether the use of an effervescent agent aids in evaluating gastric (67)Ga uptake. METHODS: Twenty patients having or suspected of having gastric uptake on whole-body (67)Ga scintigrams were studied. Anterior abdominal images were obtained at baseline and after the oral intake of the effervescent agent (gas contrast image). The presence or absence of malignant gastric uptake was judged visually using the baseline image or gas contrast image. The judgment was compared with the clinical diagnosis, and the clinical usefulness of the gas contrast technique was assessed. RESULTS: In all patients, successful distension of the stomach was indicated in the gas contrast image. Clinical assessment showed gastric lesions in six patients (gastric involvement of lymphoma in 3, primary gastric lymphoma in 2, and adenocarcinoma in 1). The gas contrast image yielded accurate judgments of malignant gastric uptake in all patients except one with adenocarcinoma. Imaging after gastric distension induced by the oral effervescent agent contributed to excluding malignant gastric uptake in eight patients and demonstrating malignant gastric uptake in four patients. CONCLUSIONS: Benign gastric uptake may complicate the assessment of gastric lesions in (67)Ga scintigraphy. Additional spot imaging after oral intake of an effervescent agent can aid in evaluating malignant gastric lesions through gastric distension. PMID- 22081276 TI - Revisiting backward recall and benchmark memory effects: a reply to Bireta et al. (2010). AB - When participants are asked to recall lists of items in the reverse order, known as backward recall, several benchmark memory phenomena, such as the word length effect, are abolished (Bireta et al. Memory & Cognition 38:279-291, 2010). Bireta et al. (Memory & Cognition 38:279-291, 2010) suggested that in backward recall, reliance on order retention is increased at the expense of item retention, leading to the abolition of item-based phenomena. In a subsequent study, however, Guerard and Saint-Aubin (in press) showed that four lexical factors known to modulate item retention were unaffected by recall direction. In a series of five experiments, we examined the source of the discrepancy between the two studies. We revisited the effects of phonological similarity, word length, articulatory suppression, and irrelevant speech, using open and closed pools of words in backward and forward recall. The results are unequivocal in showing that none of these effects are influenced by recall direction, suggesting that Bireta et al.'s (Memory & Cognition 38:279-291, 2010) results are the consequence of their particular stimuli. PMID- 22081277 TI - Differences in the strength of distractor inhibition do not affect distractor response bindings. AB - Distractor inhibition and distractor-response binding were investigated in two experiments by analyzing distractor repetition benefits and their interaction with response repetition effects in a sequential-priming paradigm. Distractor repetition benefits were larger for distractors that were incompatible with the to-be-executed response (task-related distractors) than for distractors that were not assigned to a response (neutral distractors), indicating that the strength of distractor inhibition was a function of response interference for the distractors. In contrast, the distractor-response bindings were found to be of equal strength for both task-related and neutral distractors. Thus, differences in the strengths of distractor inhibition did not affect the integration of distractors with responses into event files. Instead, our results suggest that distractor-response binding and distractor inhibition are independent mechanisms that are recruited for the automatization of behavior and action control. PMID- 22081278 TI - Tropical and unusual infections of the musculoskeletal system. PMID- 22081279 TI - Diagnostic radiology in the tropics: technical considerations. AB - An estimated two thirds of the world's population is currently without access to diagnostic radiology services, and most of them live in resource-limited tropical regions with harsh environments. Most patients are diagnosed and treated in poorly equipped government-funded hospitals and clinics that have insufficiently trained staff and are barely operational. Any available imaging equipment is likely to be functioning suboptimally and be poorly maintained. The root of the problem is usually a lack of know-how and a quality culture, combined with insufficient basic equipment and infrastructure. Radiological imaging is an essential aspect of primary care and used in the critical diagnosis and management of trauma, tuberculosis, pneumonia, acquired immunodeficiency syndrome, cancer, and other respiratory and abdominal diseases. Considerations such as quality management and infrastructure, personnel, equipment, and radiation protection and safety are important to ensure the proper functioning and rational use of a diagnostic radiology facility in the tropics. PMID- 22081280 TI - Tuberculous osteomyelitis and spondylodiscitis. AB - Tuberculosis (TB) is no longer a disease limited to developing nations and is still a major cause of significant morbidity and mortality worldwide. The indolent clinical presentation, emergence of multidrug-resistant mycobacteria, and association with human immunodeficiency virus infection poses obstacles for early diagnosis and management. Compared with the other forms of TB, musculoskeletal involvement is relatively rare. Tuberculous spondylitis is the most common form of musculoskeletal TB and accounts for ~50% of cases. Extraspinal musculoskeletal TB shows a predilection for large weightbearing joints, long bones, and the skull. This article reviews the radiologic features of diverse forms of osseous TB and the diagnostic value of the different imaging techniques. It also reviews the imaging differential diagnoses, including other infections and malignancies/metastases. Conventional radiography is of key value in the diagnosis of musculoskeletal TB. Computed tomography, magnetic resonance imaging, and bone scintigraphy also play key roles in the early detection of disease and in demonstrating the extent of disease process and soft tissue involvement. Because delay in treatment significantly reduces the cure rate and increases the rate of complications and morbidity, early radiological diagnosis of TB is of paramount importance for appropriate management. PMID- 22081281 TI - Tuberculosis arthritis and tenosynovitis. AB - The incidence of extrapulmonary tuberculosis (TB) has been rising due to the increasing number of immunosuppressed patients. Musculoskeletal system accounts for 25% of extrapulmonary TB. Most of the musculoskeletal TB involves the spine. TB of peripheral joints and tendons occur infrequently, but if untreated, it can cause serious joint and tendon destruction as well as spread of the infection to the surrounding bursa, muscle, and other soft tissues. The diagnosis of TB of joints and tendons is difficult due to the nonspecific clinical manifestations and imaging features. Concurrent active pulmonary TB is present in <50% of the patients. A positive chest radiographic finding or a positive tuberculin test supports the diagnosis, but negative results do not exclude diagnosis. Although imaging features of TB of joints and tendons are nonspecific, certain findings such as relatively preserved joint space, juxta-articular osteoporosis, cold abscesses, para-articular soft tissue calcification, and rice bodies are suggestive of TB infection. Familiarity with these imaging features can help in making an early diagnosis and facilitating proper management. PMID- 22081282 TI - Musculoskeletal brucellosis. AB - Brucellosis is a zoonosis of worldwide distribution caused by small gram-negative nonencapsulated coccobacilli of the genus Brucella. It is characterized by a granulomatous reaction in the reticuloendothelial system. Because it affects several organs and tissues, it may have various clinical manifestations. Musculoskeletal involvement is one of the most common locations, and the frequency of bone and joint (osteoarticular) involvement of brucellosis varies between 10% and 85%. Osteoarticular involvement includes spondylitis, sacroiliitis, osteomyelitis, peripheral arthritis, bursitis, and tenosynovitis. The most common osteoarticular finding in children is monoarticular arthritis, mostly located in the knees and hips; whereas in adults, sacroiliitis is the most frequent. Imaging studies, including radiography, computed tomography (CT), magnetic resonance (MR) imaging, and bone scintigraphy, have been used for diagnosis. Radiography is limited to evaluating the focal form of spinal brucellosis and advanced disease at the joints. CT and bone scintigraphy have limited value because of their inadequate soft tissue resolution. MR imaging is the method of choice to assess the extent of disease and follow up the treatment response. However, MR imaging has a low specificity to predict the exact cause of an osteoarticular lesion, and in case of arthralgia or symptoms of osteomyelitis or spondylodiscitis, the index of suspicion should be high in regions where the disease is endemic. PMID- 22081283 TI - Musculoskeletal melioidosis. AB - Melioidosis is an infectious disease caused by Burkholderia pseudomallei, mostly affecting patients in Southeast Asia and northern Australia. The disease has been increasingly recognized around the world due to the increased levels of travel and population movement. Clinical manifestations of melioidosis range from fulminant septicemic illness to an indolent local infection. The disease often involves multiple organs, including the lung, spleen, liver, and other visceral organs. Musculoskeletal infection is usually seen as a part of multiorgan involvement, but localized musculoskeletal involvement may occur. The most common manifestation of musculoskeletal melioidosis is septic arthritis, followed by osteomyelitis, pyomyositis, and soft tissue abscesses. The clinical and radiological manifestations of musculoskeletal melioidosis are nonspecific, and the diagnosis needs a high level of suspicion. Associated infection of lungs and visceral organs is suggestive of melioidosis. The disease requires special laboratory facilities and treatment. Inappropriate or inadequate treatment leads to high mortality rate or long-term relapse of the disease. The causative organism of melioidosis, clinical manifestations, and imaging features of musculoskeletal melioidosis are reviewed. PMID- 22081284 TI - Tropical pyomyositis and necrotizing fasciitis. AB - Pyomyositis is a purulent infection of skeletal muscle that arises from hematogenous spread, usually with abscess formation. Necrotizing fasciitis is a more severe, rapidly progressive infection involving the superficial and deep fascia with necrosis and fluid collections that can be life threatening if left untreated. Both conditions may coexist, and concomitant cellulitis is often seen. A high incidence of these diseases occurs in the tropics, but they are increasingly being seen in temperate countries, due in part to their association with immunodeficiency conditions such as human immunodeficiency virus (HIV) infection, diabetes mellitus, and organ transplantation. This article aims to familiarize physicians with these entities, review their clinical manifestations and imaging features, and highlight the role of imaging in the management of patients with these conditions. PMID- 22081285 TI - Musculoskeletal fungal infections. AB - Fungal infections of the musculoskeletal system are uncommon. They are often found in immunosuppressed or patients with the acquired immunodeficiency syndrome or in patients with a history of travel to an endemic region. Infections often present with multifocal chronic osteomyelitis or chronic mono- or polyarthritis resembling osteoarticular tuberculosis. A clinical clue to the correct diagnosis is the presence of overlying skin sinuses. Radiologists can suggest the correct diagnosis with a good clinical history, although a biopsy and/or fungal culture is usually necessary before beginning treatment. PMID- 22081286 TI - Musculoskeletal coccidioidomycosis. AB - Coccidioidomycosis (valley fever) is a systemic fungal infection caused by soil fungi, Coccidioides species, and is associated with significant morbidity and mortality. This infection is endemic in northern Mexico, the southwestern United States, and parts of Central and South America. The risk factors include ethnicity (especially African and Pacific Island ancestry), male gender, and immunosuppression. The primary infection occurs in lungs, but fewer than 40% of patients are symptomatic. Fewer than 1% of infections result in disseminated disease, which may involve any organ. Skeletal infection occurs in 10 to 50% of these patients and is frequently multicentric with axial skeleton involvement. The diagnosis can be confirmed by culture of the organism or visual detection from cytological or histological specimens obtained from sites of disease. A presumptive diagnosis can be made in patients with a compatible illness and a positive serologic test. Imaging plays a significant role in diagnosis and follow up treatment of musculoskeletal coccidioidomycosis and includes radiography, magnetic resonance imaging, computed tomography, and bone scintigraphy. Skeletal coccidioidomycosis is difficult to treat and frequently requires a combination of medical therapy and surgical debridement. Medical therapy must be continued for a prolonged period of time, potentially for a lifetime in some patients. PMID- 22081287 TI - Musculoskeletal hydatid disease. AB - Hydatid disease is an infectious disease caused by the larval stage of the parasitic tapeworm Echinococcosis granulosus. Its distribution is worldwide. Although hydatid disease can develop in almost any part of the body, it is most commonly found in the liver and lung. Musculoskeletal involvement is rare. The radiological appearance of the hydatid disease of musculoskeletal system mimics tumors and other inflammatory conditions. Therefore preoperative diagnosis of musculoskeletal hydatid disease is sometimes difficult clinically and radiologically. On radiography, different radiographic changes may occur. In cases of osteolytic and inflammatory changes, it may mimic any variant of nonspecific or specific osteomyelitis. Bone erosion and destruction may lead to almost complete osteolysis, bone may distort, and on occasion, its radiologic appearances may be confused with those of a malignant bone tumor. Computed tomography (CT) is more accurate in delineating the area of destruction. The primary role of CT and magnetic resonance imaging is in the recognition of extraosseous spread of the hydatid disease within the soft tissues. This article reviews the pathological basis and the clinical and imaging features of musculoskeletal hydatid disease. PMID- 22081288 TI - Musculoskeletal infection in acquired immunodeficiency syndrome. AB - Musculoskeletal infection is one of the common manifestations of patients infected with human immunodeficiency virus and acquired immunodeficiency syndrome. With immune deficiency, patients are susceptible to a variety of nonopportunistic and opportunistic infections that can result in significant morbidity and mortality. Infection can involve any anatomical compartments resulting in infectious arthritis, osteomyelitis, pyomyositis, and soft tissue and skin infection. Imaging plays an important role in the early diagnosis and treatment planning for these patients. This article reviews the clinical manifestations of musculoskeletal infection together with reported causative organisms. We discuss the role of imaging and present radiological examples. PMID- 22081289 TI - Musculoskeletal complications of severe acute respiratory syndrome. AB - The severe acute respiratory syndrome (SARS) was a highly infectious pneumonia that emerged in southern China early in 2003. A large number of SARS patients experienced large joint arthralgia, although this was, for the most part, not associated with any abnormality on magnetic resonance imaging. The main musculoskeletal complications of SARS were osteonecrosis and reduced bone mass, and these arose not from the disease per se but as a sequel to treatment of SARS with high-dose steroids. SARS patients were almost universally steroid naive with no other known predisposition to osteonecrosis. Prevalence of osteonecrosis in SARS patients treated with steroids ranged from 5% to 58%. Osteonecrosis most commonly affected the proximal femur and femoral condyles and was most strongly related to cumulative steroid dose and duration of steroid therapy. Osteonecrosis risk was <1% in patients receiving <3 g and 13% in patients receiving >3 g cumulative prednisolone-equivalent dose. Most osteonecrotic lesions tended to improve with a reduction in lesion volume over a follow-up period of 5 years. The relative reduction in osteonecrotic lesion volume was greatest for smaller lesions. PMID- 22081290 TI - Imaging-guided biopsy in musculoskeletal infections. AB - Biopsies may be required in patients suspected to have musculoskeletal infections to confirm the diagnosis and also to identify the causative organism. Imaging guided biopsies have gained increased acceptance to obtain various types of tissues for diagnosis. Under image guidance, biopsies are done percutaneously, usually under local anesthesia. They are relatively safe, and complications are significantly less compared with open biopsies. In this article, we review the planning, indications, technique, and complications of imaging-guided percutaneous biopsy performed for musculoskeletal infections. PMID- 22081291 TI - Creatine and pyruvate prevent behavioral and oxidative stress alterations caused by hypertryptophanemia in rats. AB - It is known that the accumulation of tryptophan and its metabolites is related to brain damage associated with both hypertryptophanemia and neurodegenerative diseases. In this study, we investigated the effect of tryptophan administration on various parameters of behavior in the open-field task and oxidative stress, and the effects of creatine and pyruvate, on the effect of tryptophan. Forty, 60 day-old male Wistar rats, were randomly divided into four groups: saline, tryptophan, pyruvate + creatine, tryptophan + pyruvate + creatine. Animals received three subcutaneous injections of tryptophan (2 MUmol/g body weight each one at 3 h of intervals) and/or pyruvate (200 MUg/g body weight 1 h before tryptophan), and/or creatine (400 MUg/g body weight twice a day for 5 days before tryptophan twice a day for 5 days before training); controls received saline solution (NaCl 0.85%) at the same volumes (30 MUl/g body weight) than the other substances. Results showed that tryptophan increased the activity of the animals, suggesting a reduction in the ability of habituation to the environment. Tryptophan induced increase of TBA-RS and total sulfhydryls. The effects of tryptophan in the open field, and in oxidative stress were fully prevented by the combination of creatine plus pyruvate. In case these findings also occur in humans affected by hypertryptophanemia or other neurodegenerative disease in which tryptophan accumulates, it is feasible that oxidative stress may be involved in the mechanisms leading to the brain injury, suggesting that creatine and pyruvate supplementation could benefit patients affected by these disorders. PMID- 22081292 TI - Inpatient warfarin management: pharmacist management using a detailed dosing protocol. AB - Hospitalized patients receiving anticoagulants such as warfarin are at increased risk for adverse events because of difficulties maintaining a therapeutic international normalized ratio (INR). We sought to determine whether a detailed warfarin dosing protocol administered by pharmacists with minimal physician oversight significantly reduced the proportion of hospitalized patients with a supratherapeutic INR. We conducted a prospective, nonrandomized trial with patients on cardiology, internal medicine, and family medicine inpatient services who received at least 1 dose of warfarin while hospitalized. The baseline group included 293 patients, and the intervention group comprised 217 patients. Baseline characteristics were similar in each group, except that more patients received antibiotics in the intervention group. The defect rate (INR > 5 after receiving warfarin) in the baseline group was significantly higher than in the intervention group (7.85 vs. 1.85%). Conversely, the percentage of patients with an INR less than 1.7 after 4 warfarin doses was lower in the intervention patients, indicating overall improvement in therapeutic levels. Dosing discussions were required between the pharmacist and a physician for only 6% of intervention patients. The protocol effectively reduced overanticoagulation without increasing under anticoagulation during hospitalization and reduced the need for close physician oversight. PMID- 22081293 TI - Current status on plasma biomarkers for acute mesenteric ischemia. AB - Clinical diagnosis of acute mesenteric ischemia is difficult. The aim of this review is to provide current status on the search for an accurate plasma biomarker for acute mesenteric ischemia. A search using the medical subject heading terms marker and mesenteric ischemia or intestinal ischemia or superior mesenteric artery occlusion or mesenteric venous thrombosis in the Medline and Embase databases from 1980 to 2011. Studies without a control group or a control group consisted of healthy individuals (human studies), or studies on intestinal reperfusion were excluded. Twenty animal and twelve human studies were identified. In human studies, the studied series of patients had a control group that had a need of laparotomy (n = 2), suspected acute mesenteric ischemia (n = 7), acute abdomen (n = 2) or systemic inflammatory response syndrome (n = 1). D: dimer has been found to be the most consistent highly sensitive early marker, but specificity was low. The follow-up study on alpha-glutathione S-transferase yielded inferior sensitivity and accuracy than the preliminary study, clearly questioning the value of this marker. Intestinal fatty acid binding globulin (I FABP) and D: -lactate are both interesting markers, but the results were conflicting. Different cut-off levels have been used in the studies on I-FABP. The encouraging preliminary result of cobalt-albumin and urinary FABP as an accurate marker needs to be addressed in other study populations. The early clinical and laboratory diagnosis of intestinal ischemia remains a challenge. None of the proposed plasma-derived tests for acute mesenteric ischemia has as yet entered routine clinical practice. The proposed biomarkers need to be evaluated in a prospective clinical research project in patients with acute abdomen. PMID- 22081294 TI - Relationship between preoperative radial artery and postoperative arteriovenous fistula blood flow in hemodialysis patients. AB - BACKGROUND: It is recommended that arteriovenous fistula (AVF) blood flow should be more than 425 ml/min before cannulation. However, the relationship between preoperative radial artery flow (RAF) and postoperative AVF blood flow has still not been examined. METHODS: Sixty-one patients with end-stage kidney disease (ESKD) were examined. They had an AVF prepared at Juntendo University Hospital from July 2006 through August 2007. Preoperative RAF and postoperative AVF blood flows were measured by ultrasonography. RESULTS: AVF blood flow gradually increased after the operation. AVF blood flow was significantly correlated with preoperative RAF. When preoperative RAF exceeded 21.4 ml/min, AVF blood flow rose to more than 425 ml/min. The postoperative AVF blood flow in the group with RAF of more than 20 ml/min was significantly higher than that in those with less than 20 ml/min. Preoperative RAF of less than 20 ml/min had a significantly high risk of primary AVF failure within 8 months compared with that of more than 20 ml/min. CONCLUSIONS: It appears that measurement of RAF by ultrasonography is useful for estimating AVF blood flow postoperatively and can predict the risk of complications in ESKD patients. PMID- 22081295 TI - Evaluation of growth in low-body-weight kidney transplant Egyptian children: 25 year experience. AB - BACKGROUND: Identification of problems associated with kidney transplantation in low-body-weight children is an essential step toward improving graft function and patient survival as well as quality of life. PATIENTS AND METHODS: This study comprised 63 renal transplant children weighing 25 kg or less at time of renal transplantation. All children received a living donor renal allotransplant between December 1984 and March 2009. These children were retrospectively evaluated regarding their survival, graft survival as well as physical growth. RESULTS: Our patient and graft survival rates at 1, 5 and 10 years were 98.4%, 96.8% and 96.8%, and 94.9%, 82.6% and 58.4%, respectively. Significant risk factors for growth retardation post renal transplant were identified and included older age at time of transplant (p=0.019), female sex (p=0.010), retarded growth at time of transplant (p=0.011, by univariate analysis, and p=0.028, by multivariate analysis), incidence of chronic rejection (p=0.012), higher steroid cumulative dose (p=0.013) and graft dysfunction (p=0.009, by multivariate analysis). CONCLUSION: The current final height of low-body-weight transplant Egyptian children has remained suboptimal. The management of growth retardation posttransplant is multifactorial and should start early before transplantation, with optimal care of growth in children with chronic kidney disease. Moreover, expedited transplantation, whenever indicated, and optimization of posttransplant graft function with minimal steroid exposure are essential factors which were shown to be possible using immunosuppression based on tacrolimus plus mycophenolate mofetil, after basiliximab induction. PMID- 22081296 TI - GM-CSF contributes to prompt healing of ecthyma gangrenosum lesions in kidney transplant recipient. AB - BACKGROUND: Ecthyma gangrenosum (EG) is an unusual, potentially fatal cutaneous disease, commonly associated with Pseudomonas aeruginosa septicemia. CASE REPORT: We report the case of a 61-year-old man admitted to the Nephrology Department for fever, leukopenia and inguinal and scrotal painful lesions. Physical examination revealed inguinal and scrotal macules, nodules, blisters and ulcers with central necrosis. P. aeruginosa was isolated from an ulcer. EG was diagnosed. Because of the severe leukopenia, granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered until the white blood cell count significantly increased. Based on antibiogram, intravenous ceftazidime and teicoplanin were given for 11 days. Cutaneous manifestations were completely healed in about 2 months. CONCLUSION: We suggest that the combination of GM-CSF with appropriate antibiotics can resolve EG and avoid or minimize the risk of septicemia in immunosuppressed patients. PMID- 22081297 TI - Tandem high-dose chemotherapy and autologous stem cell transplantation for anaplastic ependymoma in children younger than 3 years of age. AB - The present study evaluates the feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in very young children with anaplastic ependymoma. We aimed both to improve survival and to avoid unacceptable late adverse effects of radiation therapy (RT) by avoiding or deferring RT until 3 years of age. Five consecutive patients younger than 3 years of age with anaplastic ependymoma were enrolled from April 2006 to November 2008. Tandem HDCT/autoSCT was given following six cycles of induction chemotherapy. RT was either not given or deferred until 3 years of age if the patient was in complete response after tandem HDCT/autoSCT. Median age at diagnosis was 16 (range 12-28) months. Four patients had significant residual tumor (>1.5 cm(2)) after initial surgery, and three had leptomeningeal seeding. Toxicities during induction chemotherapy and tandem HDCT/autoSCT were manageable. No tumor progressed during induction chemotherapy and tandem HDCT/autoSCT, and RT was thus avoided or deferred until 3 years of age in all patients. All patients are alive at median follow-up of 45 (range 31-62) months from diagnosis, although tumor progressed in one patient. No significant endocrine dysfunction occurred except for hypothyroidism in one patient. Cognitive function was also acceptable in all patients but one who had significant neurologic injury during surgery. Our results indicate that treatment with tandem HDCT/autoSCT is feasible in very young children with anaplastic ependymoma and may improve the survival of patients with acceptable long-term toxicity. PMID- 22081298 TI - Imaging of human mesenchymal stromal cells: homing to human brain tumors. AB - Human mesenchymal stromal cells (hMSC) can be used as a drug delivery vehicle for the treatment of GBM. However, tracking the migration and distribution of these transplanted cells is necessary to interpret therapeutic efficacy. We compared three labeling techniques for their ability to track the migration of transplanted hMSC in an orthotopic mouse xenograft model. hMSC were labeled with three different imaging tags (fluorescence, luciferase or ferumoxide) for imaging by fluorescence, bioluminescence or magnetic resonance imaging (MRI), respectively. hMSC were labeled for all imaging modalities without the use of transfection agents. The labeling efficacy of the tags was confirmed, followed by in vitro and in vivo migration assays to track hMSC migration towards U87 glioma cells. Our results confirmed that the labeled hMSC retained their migratory ability in vitro, similar to unlabeled hMSC. In addition, labeled hMSC migrated towards the U87 tumor site, demonstrating their retention of tumor tropism. hMSC tumor tropism was confirmed by all three imaging modalities; however, MRI provides both real time assessment and the high resolution needed for clinical studies. Our findings suggest that ferumoxide labeling of hMSC is feasible, does not alter their migratory ability and allows detection by MRI. Non invasive tracking of transplanted therapeutic hMSC in the brain will allow further development of human cell based therapies. PMID- 22081299 TI - High rate of infection control with one-stage revision of septic knee prostheses excluding MRSA and MRSE. AB - BACKGROUND: The rate of infection control for one-stage revision of infected knee arthroplasties is unclear as are the factors influencing infection control. Such factors include duration of infection and the type of infected prosthesis. QUESTIONS/PURPOSES: We therefore determined: (1) the rate of infection control with one-stage revision of septic knee prostheses, (2) the clinical knee scores that can be achieved, (3) whether the duration of infection or the type of prosthesis influence the level of infection control, and (4) whether different types of prostheses influence the knee scores. METHODS: We retrospectively reviewed prospectively collected data from 63 patients who underwent one-stage revisions of septic knee endoprostheses (six unicondylar, 37 primary total knee replacement prostheses, and 20 hinged knee endoprostheses) between 2004 and 2006. All were treated locally and systemically with microorganism-specific antibiotics. For this study we excluded patients with Methicillin-resistant Staphylococcus aureus and Methicillin-resistant Staphylococcus epidermidis or unknown microorganisms. The patients were examined for infection every 3 months and Oxford and Knee Society scores were assessed at the same time. The minimum followup was 24 months (mean followup, 36 months; range, 24-70 months). RESULTS: None of the patients with replacement unicondylar and primary total knee replacement prostheses had recurrence of infection. Three of the 20 patients with the hinged infected knee prostheses had recurrences; these three patients had chronic infections and had undergone two to three revision operations during at least a 5-year period. The likelihood of infection control was influenced by the duration of infection. The mean Knee Society knee score 24 months after surgery was 72 points (range, 20-98 points), the Knee Society function score was 71 points (range, 10-100 points), and the Oxford-12 knee score was 27 points (range, 13-44 points). CONCLUSIONS: One-stage revision of septic knee prostheses achieved an infection control rate of 95% and higher knee scores than reported for two stage revisions. Higher rates of recurrent infection appeared to be associated with long-term chronic infections of hinged prostheses. PMID- 22081300 TI - Bone screws have advantages in repair of experimental osteochondral fragments. AB - BACKGROUND: Cartilage defects are created on intraarticular osteochondral fragments at the entrance holes of fixation devices when these fragments are fixed to the original sites. Conventional fixation devices hinder repair of these defects and there is a latent risk of secondary osteoarthritis. We therefore developed a novel fixation device system consisting of bone screws made of cortical bone for osteochondral fragments to improve repair of these surface defects. QUESTIONS/PURPOSES: We asked whether bone screws had advantages over poly-L-lactic acid (PLLA) screws in terms of (1) gross assessment of the surface, (2) volume and histologic quality of the repair tissue, and (3) biomechanical assessment of the tissue stiffness. METHODS: We examined gross morphology, microCT, histology, and stiffness of the repaired tissue with PLLA (n = 32) and bone (n = 32) screws in a rabbit model of osteochondral fracture, compared with normal controls (n = 16). RESULTS: Gross morphology and histology revealed better quality with bone screws than with PLLA screws. Mean repaired volumes in microCT were 70.6% +/- 14% with bone screws and 50.3% +/- 15% with PLLA screws. Average stiffness values for PLLA screws, bone screws, and normal cartilage were 1.67 +/- 0.54 N/mm, 2.63 +/- 0.42 N/mm, and 3.15 +/- 0.49 N/mm, respectively. CONCLUSIONS: Our results show better repaired tissue was observed for quality and quantity when chondral fractures were treated with bone screws than when treated with PLLA screws. CLINICAL RELEVANCE: Bone screws made of cortical bone may have applications in clinical situations for the fixation of intraarticular osteochondral fragments. PMID- 22081301 TI - Chronic inhibition of endoplasmic reticulum stress and inflammation prevents ischaemia-induced vascular pathology in type II diabetic mice. AB - Endoplasmic reticulum (ER) stress and inflammation are important mechanisms that underlie many of the serious consequences of type II diabetes. However, the role of ER stress and inflammation in impaired ischaemia-induced neovascularization in type II diabetes is unknown. We studied ischaemia-induced neovascularization in the hind-limb of 4-week-old db - /db- mice and their controls treated with or without the ER stress inhibitor (tauroursodeoxycholic acid, TUDCA, 150 mg/kg per day) and interleukin-1 receptor antagonist (anakinra, 0.5 ug/mouse per day) for 4 weeks. Blood pressure was similar in all groups of mice. Blood glucose, insulin levels, and body weight were reduced in db - /db- mice treated with TUDCA. Increased cholesterol and reduced adiponectin in db - /db- mice were restored by TUDCA and anakinra treatment. ER stress and inflammation in the ischaemic hind limb in db - /db- mice were attenuated by TUDCA and anakinra treatment. Ischaemia induced neovascularization and blood flow recovery were significantly reduced in db - /db- mice compared to control. Interestingly, neovascularization and blood flow recovery were restored in db - /db- mice treated with TUDCA or anakinra compared to non-treated db - /db- mice. TUDCA and anakinra enhanced eNOS-cGMP, VEGFR2, and reduced ERK1/2 MAP-kinase signalling, while endothelial progenitor cell number was similar in all groups of mice. Our findings demonstrate that the inhibition of ER stress and inflammation prevents impaired ischaemia-induced neovascularization in type II diabetic mice. Thus, ER stress and inflammation could be potential targets for a novel therapeutic approach to prevent impaired ischaemia-induced vascular pathology in type II diabetes. PMID- 22081302 TI - Queen volatiles as a modulator of Tetragonisca angustula drone behavior. AB - Tetragonisca angustula mating occurs during the virgin queen nuptial flight, usually in the presence of a drone congregation area (DCA). The presence of virgin queen pheromone is considered the trigger for DCA establishment, although this has not been demonstrated experimentally. We established meliponaries, in different habitats, with T. angustula virgin queens during the main drone reproduction period. Eight DCAs were observed in urban areas, and all established outside or near colonies containing at least one virgin queen. The accumulation of drones in the DCAs occurred from 08:00 to 18:00 h and over 3-35 days. The number of drones in DCAs ranged from 60 to 2,000. In field trials, drones were attracted to virgin queens and also, unexpectedly, to physogastric queens. Volatiles collected from both virgin and physogastric queens elicited strong electoantennogram (EAG) responses from drones. Virgin and physogastric queen volatiles were qualitatively similar, but quantitatively different, in chemical composition. The queen's abdomen was the principal source of these compounds. Isopropyl hexanoate (IPH), the most abundant compound in virgin queen volatiles and one of the most abundant in physogastric queen volatiles, was identified as one of the compounds that elicited EAG responses and was demonstrated to attract drones in a field test. PMID- 22081303 TI - Role of androgen receptor CAG repeat polymorphism length in hypothalamic progesterone sensitivity in hyperandrogenic adolescent girls. PMID- 22081304 TI - Severity of inducible myocardial ischemia predicts incident acute coronary syndromes in asymptomatic individuals with a family history of premature coronary artery disease. AB - BACKGROUND: Although the severity of inducible ischemia provides incremental prognostic information in persons with known or suspected coronary artery disease (CAD), its significance for predicting long-term CAD outcomes in apparently healthy populations is unknown. This study was designed to evaluate the presence and degree of myocardial ischemia in asymptomatic siblings of persons with premature CAD <60 years of age and to determine its significance for predicting incident acute coronary syndromes (ACS) during follow-up of 5 to 25 years. METHODS: Siblings (n = 1,287, age 30-59 years, 55% female) were screened for traditional risk factors, underwent exercise treadmill testing with nuclear perfusion imaging, and were followed for the development of ACS (mean follow-up 11.6 +/- 5.1 years). The severity of ischemia was assessed by semiquantitative methods using the standard 17-segment model and then categorized by the percent maximal summed stress score as none (0%), minimal (1% to <5%), mild (5% to 10%), moderate (10% to 15%), or severe (>=15%). RESULTS: ACS occurred in 132 subjects (10.3%) and included sudden cardiac death (n = 13), acute MI (n = 62), and unstable angina with revascularization (n = 57). The presence of no (88%), minimal (6%), mild (5%), and moderate/severe (1%) ischemia was associated with an ACS incidence of 8.3%, 19.7%, 25.0%, and 38.9%, respectively (P < .0001 for trend). Kaplan-Meier event-free survival analyses by myocardial ischemia severity categories showed that even minimal and mild myocardial ischemia were associated with greater ACS incidence detectable as early as 2 years after baseline. A Cox proportional hazard model, adjusted for risk factors and follow-up time, showed that each 5% increment in the severity of ischemia resulted in a 77% increase in the hazard of incident ACS (P < .001). CONCLUSION: Inducible myocardial ischemia is prevalent in asymptomatic siblings of persons with early onset CAD. Most ischemia is minimal or mild in severity, and although the severity of ischemia is associated with the risk of ACS in a graded fashion, the presence of even minimal and mild perfusion defects predicts worse CAD outcomes in this population. PMID- 22081305 TI - A highly elastic and adhesive gelatin tissue sealant for gastrointestinal surgery and colon anastomosis. AB - BACKGROUND: We describe the development of a highly elastic and adhesive surgical tissue sealant, based on photochemically crosslinked gelatin, for sealing sutured incisions in the gastrointestinal (GI) tract in a rabbit surgical model and in a canine colon anastomosis study. METHODS: The study included in vitro assessment of mechanical parameters of the tissue sealant and in vivo analysis of burst strength and histology at 24 h, 3 days and 7 days post surgery, in a rabbit model, to assess progress of wound healing at the suture sites. Utility of this sealant to repair and seal a lower colonic resection and anastomosis procedure in a canine model was also investigated. RESULTS: We show that a photopolymerised gelatin tissue sealant provides effective sealing of GI incisions and facilitates wound healing with no evidence of inflammation up to 28 days post-surgery. Blending of derivatised gelatin with underivatised gelatin allowed tuning of elasticity and elastic modulus of the photopolymerised sealant to suit surgical applications. High tissue adhesive strength was maintained at all blend ratios and exceeded 100 kPa. CONCLUSIONS: This highly elastic and adhesive photopolymerised gelatin tissue sealant offers a number of advantages over currently available sealants suitable for GI surgical procedures. PMID- 22081306 TI - An examination of the thermodynamics of fusion, vaporization, and sublimation of ibuprofen and naproxen by correlation gas chromatography. AB - The vaporization enthalpies of (S)-ibuprofen and (S)-naproxen measured by correlation gas chromatography at T = 298.15 K are reported and compared with literature values. Adjustment of the fusion enthalpies of (RS)- and (S)-ibuprofen and (S)-naproxen to T = 298.15 K and combined with the vaporization enthalpy of the (S)-enantiomer of both ibuprofen and naproxen also at T = 298.15 K resulted in the sublimation enthalpies of both (S)-enantiomers. On the assumption that the vaporization enthalpy of the racemic form of ibuprofen is within the experimental uncertainty of the chiral form, the sublimation enthalpy of racemic ibuprofen was also evaluated. The vaporization and sublimation enthalpies compare favorably to the most of the literature values for the racemic form of ibuprofen but differ from the value reported for chiral ibuprofen. The literature values of (S) naproxen are somewhat smaller than the values measured in this work. The following vaporization enthalpies were measured for (S)-ibuprofen and (S) naproxen, respectively: DeltaH(vap) (298.15 K), 106.0 +/- 5.5, 132.2 +/- 5.0 kJ.mol(-1) . Sublimation enthalpies of 122.7 +/- 5.6 and 155.2 +/- 7.1 kJ.mol(-1) were calculated for the (S)-enantiomers of ibuprofen and naproxen and a value of 128.9 +/- 5.8 kJ.mol(-1) was estimated for the racemic form of ibuprofen. PMID- 22081307 TI - Lactobacillus plantarum and Lactobacillus buchneri as expression systems: evaluation of different origins of replication for the design of suitable shuttle vectors. AB - The objectives of this study were to establish transformation protocols for Lactobacillus plantarum CD033 and Lactobacillus buchneri CD034, two industrial silage strains and to test the influence of selected origins of replication on plasmid copy number, plasmid stability, and plasmid incompatibility in these strains. Electro-transformation protocols were optimized by examination of the influence of different electroporation solutions and cell wall weakening agents on transformation efficiency. Using Lithium acetate as cell wall weakening agent, we could achieve transformation efficiencies of 8 * 10(4) transformants per 1 MUg DNA for L. buchneri CD034 which is to our knowledge the highest described for this species up to now. In order to test feasibility of previously described origins of replication derived from Bacillus subtilis, L. plantarum, Lactococcus lactis, and two novel L. buchneri CD034 plasmids to drive replication in our two selected Lactobacillus strains, six shuttle vectors were constructed. Results indicate that, in terms of stable propagation and high gene copy numbers (up to 238 copies/chromosome), the most suitable origins of replication for the construction of expression vectors for the selected silage strains were the ones derived from the novel L. buchneri CD034 plasmids. PMID- 22081308 TI - Obstructive sleep apnea and the metabolic syndrome. PMID- 22081309 TI - CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function. AB - Myeloid-derived suppressor cells (MDSCs) are a subpopulation of myeloid cells with immunosuppressive function whose numbers are increased in conditions such as chronic infection, trauma, and cancer. Unlike murine MDSCs defined as CD11b(+)/Gr 1(+), there are no specific markers for human MDSCs. The goal of this study was to delineate a specific human MDSCs subpopulation in granulocytes from terminal cancer patients and investigate its clinical implications. Here, we show that the CD15(+)/CD16(low) subset was increased in terminal cancer patients compared with healthy donors (P = 0.009). Phorbol 12-myristate 13-acetate-activated granulocytes (CD16(low)/CD66b(++)/CD15(+)) that have a phenotype similar to MDSCs from cancer patients, effectively suppressed both proliferation and cytotoxicity of normal T cells. Among cancer patients, T-cell proliferation was highly suppressed by granulocytes isolated from terminal cancer patients with a high proportion of CD15(+)/CD16(low) cells. Patients with low peripheral blood levels of CD15(+)/CD16(low) cells had significantly longer survival than those with high levels (P = 0.0011). Patients with higher levels of CD15(+)/CD16(low) also tended to have poor performance status (P = 0.05). These data suggest that CD15(+)/CD16(low) granulocytes found in terminal cancer patients may play a role in the progression of cancer by inhibiting tumor immunity. PMID- 22081310 TI - Podoplanin expression during dysplasia-carcinoma sequence in the oral cavity. AB - Human podoplanin, a type-1 transmembrane sialomucin-like glycoprotein, is involved in cell migration, tumor cell invasion, and metastasis. However, the role of the protein in squamous cell carcinoma (SCC) has been unclear and immunohistochemical reactivity for podoplanin differs from organ-to-organ. In the present study, immunohistochemical and molecular biological analyses were performed to examine the importance of podoplanin expression in oral precancerous and cancerous lesions and metastases. We immunohistochemically investigated the expression of podoplanin in 103 precancerous lesions, 69 primary oral squamous cell carcinomas (OSCCs), and 32 metastases, and that of E-cadherin and vimentin in primary OSCCs with metastasis. Furthermore, human OSCC-derived cell lines preincubated with fibrous growth factor-basic, epidermal growth factor (EGF), and tumor growth factor-beta1 were subjected to real-time reverse transcription polymerase chain reaction. Immunoreactivity for podoplanin was detected in 89 (86.4%) of the precancerous lesions and the intensity was correlated with the degree of epithelial dysplasia (P = 0.016). Enhanced podoplanin expression was observed in 66 (95.7%) of the OSCCs and was significantly associated with a poor pathologic grade of differentiation (P = 0.020). Epithelial-mesenchymal transition was observed in 18 (58.1%) of the primary OSCCs with metastasis to regional lymph nodes. Messenger RNA for podoplanin was markedly increased after treatment with EGF in three OSCC cell lines. The present findings suggest that podoplanin is associated with tumor development via the oral dysplasia-carcinoma sequence and could be involved in a signaling pathway governing tumor growth and invasion in OSCC. PMID- 22081311 TI - SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues. AB - In the present study, we investigated mRNA expression patterns of both SOCS5 and SOCS6 in various normal and cancer tissues using a commercially available Cancer Profiling Array. We found that SOCS5 and SOCS6 had similar expression patterns in most cancer and healthy individuals, suggesting that these two genes are transcriptionally co-regulated. Tissue-specific up- or down-regulation of SOCS5 and SOCS6 was observed in several cancer tissues. Most importantly, thyroid gland cancer tissues exhibited large reductions of both SOCS5 and SOCS6 expressions. In addition, mRNA and protein levels of SOCS6 were down-regulated in liver cancer tissues. The results from our study may contribute to understanding SOCS5 and SOCS6 expression regulation in various cancer tissues, and show that these two factors may be used for diagnosing cancer. PMID- 22081312 TI - Purification and biochemical characterization of an organic-solvent-tolerant thioredoxin from dromedary pancreas. AB - We purified to homogeneity and characterized a heat stable thioredoxin which catalyzes thiol/disulfide exchange reaction, for the first time from dromedary pancreas. The purification involved heat and acidic treatment (90 degrees C; pH 2.5), precipitation by ammonium sulphate and ethanol, respectively followed by sequential column chromatography reverse HPLC column, and it resulted in an apparently pure protein after a 217-fold purification with a final yield of 55% of the initial thioredoxin activity. The thioredoxin preparation obtained was homogeneous as judged by polyacrylamide gel electrophoresis and the presence of valine as the only NHt-terminal amino acid. MALDI-TOF mass spectrometry revealed that the protein has a molecular mass of 11,302.9 Da. The first 40 amino-acid residues at the N-terminal extremity of purified DrTrx was determined by automatic Edman degradation and showed a high sequence homology with known Thioredoxin. It contained he tetrapeptide-Cys-Gly-Pro-Cys-, which constitutes the active site of mammalian thioredoxins. DrTrx activity was compatible with the presence of organic solvents and the maximum activity appeared at pH 7.5 using the insulin precipitation assay. Thioredoxin stability in the presence of organic solvents, as well as in acidic and alkaline pHs and at high temperatures makes it a good candidate for its application in pharmaceutical and food industry. PMID- 22081313 TI - Isolation of galectin-1 from human platelets: its interaction with actin. AB - Galectins are a family of animal lectins defined by their beta-galactoside binding specificity and a consensus sequence in their carbohydrate-recognition domain. Galectin-1 (Gal-1) is expressed as a non-covalently linked homodimer present in a variety of tissues. Here we describe its isolation from human platelets by a procedure involving ionic exchange chromatography and affinity chromatography on lactose-agarose. Platelet Gal-1 co-purifies with actin, forming an actin-Gal-1 complex which does no dissociate even after treatment with sodium dodecyl sulfate. The presence of both proteins was confirmed by Western blot and by trypsin digestion followed by mass spectrometry identification. By hemagglutination assays we studied the response of recombinant Gal-1/actin, mixed and pre-incubated in different proportions, and then tested against neuraminidase treated rabbit red blood cells. The complex formation was confirmed by confocal microscopy, showing that both proteins co-localised in resting platelets as well as in thrombin-activated ones. These results suggest that endogenous Gal-1 forms an intracellular complex with monomeric actin and that, after platelet activation, Gal-1 could play a role in the polymerization-depolymerization process of actin, which concludes in platelet aggregation. PMID- 22081314 TI - Are ICSI adolescents at risk for increased adiposity? AB - BACKGROUND: Puberty is a critical period for the development of cardio-metabolic disturbances, including a more central body fat distribution. It is still unclear if IVF and more specifically ICSI, can permanently and detrimentally affect body fat accumulation in the human offspring. Therefore, adiposity and body fat distribution in 14-year-old adolescents born after ICSI were investigated. METHODS: Body composition data, including anthropometry (weight, height and BMI), skinfold thicknesses (peripheral: triceps and biceps skinfolds; central: supra iliacal and subscapular skinfolds; total: sum of the four skinfolds) and circumferences (waist, mid-upper arm) were compared between 217 ICSI singletons (116 boys, 101 girls) and 223 singletons (115 boys, 108 girls) born after spontaneous conception (SC). ICSI teenagers were part of a previously published ICSI cohort followed since birth; SC controls were recruited from schools in the surroundings. RESULTS: Among all boys, no differences in body composition measurements were found between the ICSI and SC group, taking into account confounding variables. In boys with more advanced pubertal stages, a significantly higher sum of peripheral skinfolds was found in the ICSI group compared with the SC group (difference 3.5 mm, 95% confidence interval 0.3-6.6). In girls, peripheral adiposity assessed by skinfolds and mid-upper arm circumference, and central adiposity assessed by skinfolds and waist circumference as well as total adiposity assessed by BMI, the sum of four skinfold thicknesses and skinfold-derived body fat percentage were significantly higher in the ICSI group compared with the SC group, taking into account confounding variables (all P< 0.05). Neither parental nor early life factors could explain the differences. CONCLUSIONS: We found that pubertal ICSI girls were more prone to central, peripheral and total adiposity compared with their SC counterparts. ICSI adolescents with advanced pubertal stages showed more peripheral adiposity. Continued monitoring of body fat patterns in adolescents born after fertility treatment is mandatory in order to assess their risk for developing obesity and its related adverse health effects in adulthood. PMID- 22081315 TI - Concerted evolution of satellite DNA in Sarcocapnos: a matter of time. AB - SarkOne is a genus-specific satellite-DNA family, isolated from the genomes of the species of the genus Sarcocapnos. This satellite DNA is composed of repeats with a consensus length of 855 bp and a mean G+C content of 52.5%. We have sequenced a total of 189 SarkOne monomeric repeats belonging to a total of seven species of the genus Sarcocapnos. The comparative analysis of these sequences both at the intraspecific and the interspecific levels have revealed divergence patterns between species are proportional to between-species divergence according to the phylogeny of the genus. Our study demonstrates that the molecular drive leading to the concerted-evolution pattern of this satellite DNA is a time dependent process by which new mutations are spreading through genomes and populations at a gradual pace. However, time is a limiting factor in the observation of concerted evolution in some pairwise comparisons. Thus, pairwise comparisons of species sharing a recent common ancestor did not reveal nucleotide sites in transitional stages higher than stage III according to the Strachan's model. By contrast, there was a gradation in the percentage of upper transition stages (IV, V, VI) the more phylogenetically distant the species were. In addition, closely related species shared a high number of polymorphic sites, but these types of sites were not common when comparing more distant species. All these data are discussed in the light of current life-cycle models of satellite DNA evolution. PMID- 22081316 TI - Effect of adaptation strategies when feeding fresh cassava foliage on intake and physiological responses of lambs. AB - The objective of the experiment was to study different adaptation strategies to avoid HCN intoxication when feeding fresh cassava foliage to sheep. Twenty-four Phan Rang lambs (initial weight = 19.6 kg at 5.5 months of age) were used in the study. The four experimental diets contained guinea grass (Panicum maximum) supplemented with concentrate at 1.5% of body weight (BW) as dry matter (DM) (control) or supplemented with fresh cassava foliage (FCF) that was introduced into the diet with an adaptation period of 0 (FCF-0), 7 (FCF-7) or 21 (FCF-21) days before reaching the target feeding level of 2% of BW. The average intake of FCF expressed as DM was not different amongst the supplemented treatments and ranged from 1.4 to 1.5% of BW but gradually increased during the first 7 days without any adaptation. The hydrogen cyanide consumed varied from 5.1 to 5.4 mg/kg BW and no difference between treatments with cassava foliage in the diet was found. The live weight gain was significantly higher in the treatments control and FCF-7 compared to FCF-21. No significant differences in heart rate, respiration rate and rumen movement were found between diets. The thiocyanate concentration in the urine of the lambs increased concomitantly with the increase in fresh cassava foliage offered during the first part of the experiment. In conclusion, an adaptation period of approximately 7 days seems to be favourable in combined diets where cassava foliage is offered in quantities up to 2% of BW. This level of intake could enhance the intake and LWG of the lambs without any documented effects on heart rate, respiration rate or rumen movements. PMID- 22081317 TI - Biodiversity and prevalence of parasites of domestic pigeons (Columba livia domestica) in a selected semiarid zone of South Khorasan, Iran. AB - Five species of nematodes and cestodes were collected from alimentary canals of pigeons: the nematodes were two species: Ascaridia colombae (16.66%) and Hadjelia truncata (1.96%), while the cestodes were Cotugnia digonopora (13.79%), Raillietina magninumida (18.62%) and Raillietina achinobothridia (32.35%); fecal examination revealed: Eimeria spp. (40.19%) and Cryptosporidium oocysts (2.94%); and blood smears showed: Haemoproteus cloumbae (47/05%); in mouth, throat and larynx: Trichomonans gallinae (57.84%); four species of ectoparasites were collected from feathers and subcutaneous nodules as follows: feathers: Pseudolynchia canariensis (63.72%), Columbicola columbae (79.41%), Menopen gallinea (44.11%); subcutaneous nodules: Laminosioptes cysticola (1.96%). From the parasitic fauna identified in this study, it is imperative to institute an integrated parasitic control through constant changing of litter, regular use of antihelminthics, anticoccidials and dusting of birds with pesticides. PMID- 22081318 TI - Management, productivity and livelihood effects on Kenyan smallholder dairy farms from interventions addressing animal health and nutrition and milk quality. AB - We aimed to describe the management and productivity of this group of smallholder dairy farmers in Kenya at the beginning of an intervention program and to document relevant observed changes in the 3rd year of the intervention. A 3-year intervention program, focused on management of animal health and nutrition, and milk quality, was implemented by one Kenyan and two Canadian non-governmental organizations (one university based) to help improve the milk production and livelihoods of Kenyan smallholder dairy farmers (primarily women). Thirty farmers were enrolled and completed questionnaires at the start and end of the project. Focus groups were also conducted to obtain qualitative information on livelihood effects from the program. In 2004, 70% of the eligible youngstock (more than 15 months of age) were pregnant, and cows had a long average days-in-milk of 240 days. External parasites, poor hygiene, and long claws were not uncommon among cows, and 37% and 20% of the farms reported clinical intestinal parasitism and diarrhea in youngstock. In 2006, there were significant improvements in the proportion of farms planting high-protein forages, farms using better milking procedures, and on-farm milk storage methods. The reported mastitis incidence rate fell from 0.55 to 0.20 cases/cow-year (p < 0.01), and the average number of cows and youngstock significantly increased from 1.5 and 0.9 to 2.9 and 2.6, respectively. There were reported improvements in the livelihoods among the member families. The partnership-based intervention program significantly improved management and productivity of this group of smallholder dairy farmers in rural Kenya, leading to reported livelihood benefits. PMID- 22081319 TI - Reproductive performance in sows in relation to Japanese Encephalitis Virus seropositivity in an endemic area. AB - Japanese Encephalitis Virus (JEV) is considered an important reproductive pathogen in pigs. Most studies of the reproductive impact of JEV have been conducted in areas where the disease occurs in seasonal epidemics. In this study, the associations between seropositivity for JEV, measured with an IgG ELISA, and the number of piglets born alive and stillborn were investigated in a tropical area endemic for JEV in Vietnam. Sixty percent of sows from four farms in the Mekong delta of Vietnam were seropositive to JEV and the Odds Ratio for a sow being infected was highest (6.4) in sows above 3.5 years (95% confidence interval 2.2-18.3). There was an association between increasing Optical Density (OD) values from the ELISA and the number of stillborn piglets in sows less than 1.5 years, but no effect of seropositivity could be shown when all sows were studied. OD values had an effect (p = 0.04) on the number of piglets born alive in the statistical analysis only when interacting with the effect of the breeds. An increase in mean OD value of the herd was correlated (p < 0.0001) with an increase in the number of piglets born alive. In this study, there was evidence of a negative association between seropositivity for JEV and the reproductive performance only in sows less than 1.5 years in endemic areas. This could be explained by a year-round infection with the virus, which would lead to immunity in many gilts before their first pregnancy. This, in turn, may imply that JEV infection in pigs is of minor importance for the reproductive performance in endemic areas. PMID- 22081320 TI - Allopregnanolone potentiates the glutamate-mediated seizures induced by 4 aminopyridine in rat hippocampus in vivo. AB - Excitatory and inhibitory neurotransmission in the central nervous system can be modulated by neurosteroids. We previously found that in rat hippocampal slices allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), a positive GABA(A) receptor modulator, suppresses the epileptic discharges induced by 4 aminopyridine (4-AP), a convulsant K(+) channel blocker that stimulates glutamate release. Here, we tested the action of allopregnanolone on the epileptogenic and excitotoxic effects of the intrahippocampal administration of 4-AP in vivo. Drugs were perfused by a microdialysis cannula-electrode in the dorsal hippocampus and the EEG was recorded. Extracellular levels of aspartate, glutamate and GABA were analyzed by HPLC in the microdialysis fractions, and 24 h after the experiment the hippocampus was studied histologically. 4-AP induced intense epileptic discharges, increased the extracellular levels of aspartate, glutamate, and GABA by 383, 420, and 245%, respectively, and produced a notable neurodegeneration in CA1 and CA3 areas. Allopregnanolone administration alone did not affect the electrical activity, amino acids levels or cellular morphology, but when co infused with 4-AP incremented 55-77% the duration of the epileptic discharges, and potentiated 32-49% the release of glutamate in comparison with 4-AP alone. The 4-AP-induced neurodegeneration was not modified by allopregnanolone. The NMDA receptor antagonist MK-801 protected against the epilepsy and neurodegeneration produced by 4-AP, and allopregnanolone did not affect this protection. We conclude that, differently from the observations in vitro, allopregnanolone potentiated the stimulatory effect of 4-AP on glutamate release and that this may explain the potentiation of the epileptogenic effect of 4-AP in vivo. PMID- 22081321 TI - Protein deprivation attenuates Hsp expression in fat tissue. AB - For ruminants, dietary protein is the first limiting component to the utilization of low-quality forage. Throughout gestation, low-protein intake may result in prenatal programming that causes various metabolic disturbances and physiological modulations to dams and their developing embryos. We studied the effect of long term low-protein diet (LPD) on physiological, biochemical, and molecular parameters of the energy status in gestating beef cows. LPD resulted in significant reductions in feed intake and heart rate and promoted a negative retained energy status already after 3 weeks. Elevated levels of plasma creatinine and non-esterified fatty acids indicate endogenous degradation of fat and protein as a response to the demands in energy and nitrogen. Increasing levels of beta-hydroxybutyrate confirmed the negative energy status obtained by the physiological measurements. At the molecular level, subcutaneous fat, Hsp90, Hsp70, and proteasome subunits decreased significantly after 3 months on LPD, in parallel with an increase of adipocyte fatty acid-binding protein. These results may indicate a decrease in turn-over of proteins, at the cost of induced lipolysis, and suggest that the response to protein deprivation, when examined in an energy-storing tissue, includes downregulation of the constitutive heat shock proteins involved in the protein degradation pathway of energy production and upregulation of tissue-specific genes such as those involved in energy production from fat degradation. PMID- 22081322 TI - Simultaneous transcatheter aortic and mitral valve-in-valve implantation in a patient with degenerated bioprostheses and high surgical risk. AB - Transcatheter valve-in-valve implantation is evolving as a promising alternative to reoperative valve replacement in selected high-risk patients, considering the increasing need for redo surgery due to bioprosthetic degeneration in the future. Reoperative double valve replacements are particularly associated with an elevated surgical risk. The transapical access provides the opportunity to approach the aortic and mitral valves during one intervention. We report the case of a successful transcatheter valve-in-valve implantation in the aortic and mitral position within a single procedure. PMID- 22081323 TI - Inflammatory response in transapical transaortic valve replacement. AB - OBJECTIVE: Transapical aortic valve implantation (TA-AVI) has become a fast growing alternative to conventional aortic valve replacement (cAVR) particularly for patients burdened with serious comorbidities. We investigated whether the inflammatory response triggered by TA-AVI reflects the less invasive nature of this procedure. METHOD: In this prospective observational study 25 patients undergoing aortic valve replacement (AVR; 15 cAVR and 10 TA-AVI) were included. Serial plasma cytokine concentrations (IL-6, IL-8, and IL-10) were measured by commercially available enzyme-linked immunosorbent assay kits at six different time points before, during, and after surgery. RESULTS: Plasma levels of all three cytokines increased during and after both procedures and returned to baseline before the patient's discharge. Peak values of IL-6 were 258 +/- 113 pg/mL in AVR patients versus 111 +/- 101 pg/mL in TA-AVI patients and were reached 12 hours after surgery. For IL-8, peak values were 51 +/- 29 pg/mL 1 hour after surgery in AVR patients versus 15 +/- 20 pg/mL on wound closure in TA-AVI patients. Plasma levels of IL-6 and IL-8 were significantly reduced in the TA-AVI group as compared with cAVR. IL-10 is markedly activated in both groups yet its induction is more prominent in AVR patients with peak values of 51 +/- 28 pg/mL for AVR versus 24 +/- 18 pg/mL for TA-AVI on wound closure. CONCLUSION: TA-AVI compared with cAVR results in a significant reduction but not elimination of a systemic inflammatory response, which is attributable to cardiopulmonary bypass dependent and bypass-independent factors. PMID- 22081324 TI - Decarboxylation of ferulic acid to 4-vinyl guaiacol by Streptomyces setonii. AB - 4-vinyl guaiacol (3-methoxy 4-hydroxystyrene) can be obtained by decarboxylation of ferulic acid by the strain Streptomyces setonii ATCC 39116. The formation of this metabolite was favoured by microaerobic conditions and the culture medium employed, increasing progressively the product concentration from 543.3 up to 885.1 mg/l when aeration level was diminished, reaching a highest volumetric productivity of 70.4 mg/l h and a product yield of 1.11 mol/mol. The identity of the metabolite was confirmed by gas chromatography-mass spectrometry. A metabolic study of ferulic acid and the main degradation products (ferulic acid, 4-vinyl guaiacol, protocatechuic acid, vanillyl alcohol, vanillic acid and vanillin) suggested that ferulic acid was the only substrate capable to be transformed into 4-vinyl guaiacol by this strain of S. setonii. PMID- 22081325 TI - Adding value to the oil cake as a waste from oil processing industry: production of lipase and protease by Candida utilis in solid state fermentation. AB - Olive oil cake is a by-product from the olive oil processing industry and can be used for the lipase and protease production by Candida utilis in solid state fermentation. Different carbon and nitrogen sources were evaluated, and the results showed that the supplementation of the substrate with maltose and starch as carbon sources and yeast extract as a nitrogen source significantly increased the lipase production. The best results were obtained with maltose, whereas rather low lipase and protease activities were found with glucose and oleic acid. Response surface methodology and a five-level-three-factor central composite rotatable design were used to evaluate the effects of the initial moisture content, inoculum size and fermentation time on both lipase and protease activity levels. A lipase activity value of ~25 U g(-1) and a protease activity value of 110 U g(-1) were obtained under the optimized fermentation conditions. An alkaline treatment of the substrate appeared to be efficient, leading to increases of 39% and 133% in the lipase and protease production, respectively. The results showed that the olive cake could be a good source for enzyme production by solid state fermentation. PMID- 22081326 TI - Development of Saccharomyces cerevisiae producing higher levels of sulfur dioxide and glutathione to improve beer flavor stability. AB - Sulfur compounds, such as sulfite (SO(2)), hydrogen sulfide (H(2)S), and glutathione (GSH), play different roles in beer flavor stability. SO(2) and GSH have antiaging effects which are helpful to improve the flavor stability of beer, whereas H(2)S is undesirable to beer flavor because of its unpleasant aroma. Here, we report the development of Saccharomyces cerevisiae which produces higher levels of SO(2) and GSH but lower level of H(2)S to improve beer flavor stability by nongenetic engineering approaches. After two rounds of UV mutagenesis coupled with specific plate screening methods, one promising mutant named MV16 was obtained. Compared with the original strain, the SO(2) and GSH production of MV16 in fermenting liquor increased by 31% and 30.2%, respectively, while H(2)S content decreased by 74.9%, and the DPPH radical clearance and the resistance staling value of beer fermented by MV16 increased by 24.6% and 33.0%, respectively. The antioxidizability of the mutant was improved significantly. The strategy adopted in our study could be used to obtain S. cerevisiae of improved antiaging properties, and the mutant would be safe for public use. PMID- 22081327 TI - Purification and characterization of a mannose recognition lectin from Oreochromis niloticus (tilapia fish): cytokine production in mice splenocytes. AB - The aim of this work was to purify and partially characterize a mannose recognition lectin from Nile tilapia (Oreochromis niloticus) serum, named OniL. OniL was isolated through precipitation with ammonium sulfate and affinity chromatography (Concanavalin A-Sepharose 4B). In addition, we evaluated carbohydrate specificity, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) profiles, and in vitro immunomodulatory activity on mice splenocyte experimental cultures through cytotoxic assays and cytokine production. The ammonium sulfate fraction F2 showed the highest specific hemagglutinating activity (331) and was applied to affinity matrix. Adsorbed proteins (OniL) were eluted with methyl-alpha-D: -mannopyranoside. OniL, a 17-kDa protein by SDS-PAGE constituted by subunits of 11 and 6.6 kDa, showed highest affinity for methyl-alpha-D: -mannopyranoside and D: -mannose. Immunological assays, in vitro, showed that OniL did not show cytotoxicity against splenocytes, induced higher IFN-gamma production and lower IL-10 as well as nitrite release. In conclusion, OniL lectin was successfully purified and showed a preferential Th1 response in mice splenocytes. PMID- 22081328 TI - Determination of dimethyl phthalate in environment water samples by a highly sensitive indirect competitive ELISA. AB - Recent controversy over the discovery of clouding agents containing the banned chemical di(2-ethylhexyl) phthalate in beverages in 2011 in Taiwan has caused public concerns. For the detection of dimethyl phthalate (DMP) in environment water samples, an indirect competitive enzyme-linked immunosorbent assay (ic ELISA) was developed in this paper. Dimethyl 4-aminophthalate (4-DMAP) was covalently attached to bovine serum albumin as immunogen by a diazotization method. The conjugation of DMAP and ovalbumin as coating antigen was obtained in the same way. Polyclonal antibody was obtained from New Zealand white rabbits. Under the optimized conditions, DMP was detected in the concentration range of 0.02-419 ng/mL with a detection limit of 0.01 ng/mL. The proposed method has been applied to the analysis of river water, lake water, and rain water samples. Satisfactory recoveries were obtained ranging from 90.6% to 105.5%. The cross reactivities of the anti-DMP antibody to seven structurally related phthalate esters were below 10%. The data demonstrated that the ic-ELISA method described in our study is a simple, sensitive, and specific method and showed that this assay is a reliable tool to detect DMP in water samples. PMID- 22081329 TI - An optimum fermentation model established by genetic algorithm for biotransformation from crude polydatin to resveratrol. AB - Natural resveratrol is widely used in medicine, food, and cosmetic because of its pharmacological properties. Due to its low content in plants, this study was conducted to increase the yield of resveratrol by microorganism transformation. Fungi Aspergillus niger AN-2436 was employed in biotransformation to produce resveratrol from polydatin, and genetic algorithm (GA) was used to optimize the fermentation conditions. A transformation ratio of higher than 95% was achieved in the following conditions: culture temperature of 30.3 degrees C, inoculum size of 20% (v/v), rotating speed of 147 rpm, and cultivation time of 36 h. Compared with the polydatin absorbance under the experimental conditions obtained by single-factor, orthogonal experiments and average absorbance, the GA provides the optimum experimental conditions, under which the largest transformation rate was achieved. The final transformation product obtained was identified as resveratrol, and it was proved by high-performance liquid chromatography, infrared, mass spectrometry, and nuclear magnetic resonance. PMID- 22081330 TI - Production and characteristics of the whole-cell lipase from organic solvent tolerant Burkholderia sp. ZYB002. AB - The thermostable and organic solvent tolerant whole-cell lipase (WCL) was produced by Burkholderia sp. ZYB002 with broad spectrum organic solvent tolerance. The production medium of the WCL was primarily optimized, which resulted in the maximum activity of 22.8 U/mL and the 5.1-fold increase of the WCL yield. The optimized culture medium was as follows (% w/v or v/v): soybean meal 2, soybean oil 0.5, manganese sulfate 0.1, K(2)HPO(4) 0.1, olive oil 0.5, initial pH 6.0, inoculum density 2, liquid volume 35 mL in 250-mL Erlenmeyer flask, and incubation time 24 h. The biochemical characterization of the WCL from Burkholderia sp. ZYB002 was determined, and the results showed that the optimal pH and temperature for lipolytic activity of the WCL was 8.0 and 65 degrees C, respectively. The WCL was stable at temperature up to 70 degrees C for 1 h and retained 79.2% of its original activity. The WCL was highly stable in the pH range from 3.0 to 8.5 for 6 h. Ca(2+), K(+), Na(+), NO (3) (-) , etc. ions stimulated its lipolytic activity, whereas Zn(2+) ion caused inhibition effect. The WCL was also relatively stable in n-butanol at a final concentration of 50% (v/v) for 24 h. However, the WCL was strongly inhibited in Triton X-100 at a final concentration of 10% (v/v). The WCL with thermal resistance and organic solvent tolerance showed its great potential in various green industrial chemical processes. PMID- 22081331 TI - A laccase of Fomes durissimus MTCC-1173 and its role in the conversion of methylbenzene to benzaldehyde. AB - A laccase has been purified from the liquid culture growth medium containing bagasse particles of Fomes durissimus. The method involved concentration of the culture filtrate by ultrafiltration and anion exchange chromatography on diethyl aminoethyl cellulose. The sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and native polyacrylamide gel electrophoresis both gave single protein band indicating that the enzyme preparation was pure. The molecular mass of the purified laccase determined from SDS-PAGE analysis was 75 kDa. Using 2,6-dimethoxyphenol as the substrate, the determined K (m) and k (cat) values of the laccase are 182 MUM and 0.35 s(-1), respectively, giving a k (cat)/K (m) value of 1.92 * 10(3) M(-1) s(-1). The pH and temperature optimum were 4.0 and 35 degrees C, respectively. The purified laccase has yellow colour and does not show absorption band around 610 nm found in blue laccases. Moreover, it transformed methylbenzene to benzaldehyde in the absence of mediator molecules, property exhibited by yellow laccases. PMID- 22081332 TI - Genotypes and allele frequencies of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism among Bahraini population with type 2 diabetes mellitus and related diseases. AB - Insertion/deletion (I/D) polymorphism, of a 287-bp Alu repetitive sequence in intron 16 of the angiotensin-converting enzyme (ACE) gene has been shown to be associated with different types of diseases and has been widely investigated in different populations with different ethnic origins. Various reports were published suggesting inter-ethnic variations in the frequency of allelic forms of the ACE gene. The goal of this study was to test the distribution of alleles and the different genotypes of ACE (I/D) polymorphism in Bahraini subjects and compare the results with those obtained from other population studies. The Bahraini population is an Arabic peninsula population with a high prevalence of T2DM and hypertension. A total of 560 unrelated Bahraini individuals were recruited in this study and the presence (insertion)/absence (deletion) (I/D) polymorphism of a 287-bp Alu1 element inside intron 16 of the ACE gene was done by PCR-based assays and the presence or absence of the genotypes were analyzed by the gel electrophoresis. The distribution of II, ID, and DD genotypes showed differences among Bahraini subjects, and the frequency of the D allele was significantly (P < 0.05) higher in the studied group. The results obtained for the D allele are consistent with those obtained from previous studies among Arabs, Africans, and Caucasians, but differs significantly (P < 0.05) from those in Japanese and Chinese, thus proving the ethnic variation in the distribution of the ACE alleles in different populations. PMID- 22081333 TI - Diverse H. pylori strains, IL-10 promoter polymorphisms with high morbidity of gastric cancer in Hexi area of Gansu Province, China. AB - In Hexi area of Gansu Province, people have a higher susceptibility of gastric cancer than people in the rest area of China. There is substantial geographic variation in the incidence of gastric cancer. In this article, the present author explored the roles of H. pylori infection and IL-10 promoter polymorphisms in development of gastric cancer in this area. A total of 304 participants were admitted to our study, and they were divided into two groups: control group and case group. Blood samples from all subjects were collected for gene extraction using DNA extraction kits. IL-10 polymorphisms were determined by SNaPshot Multiplex. To test H. pylori infection and its typing H. pylori antibody Immunoblotting Kits were used. This research suggested that environmental factor played an important role in the pathogenesis of gastric carcinoma in the area, H. pylori infection increased the risk of gastric cancer (OR = 2.612, 95% CI 1.636 4.170) and subject with H. pylori I-type positive was at significantly higher risk for progression to gastric cancer (OR = 4.712, 95% CI 2.656-8.537). For subjects with the ATA/GCC or GCC/GCC haplotype of the IL-10-1082/-819/-592 polymorphism relative to the ATA/ATA haplotype group, the risk of gastric cancer development was significantly increased. It has been demonstrated that the presence of IL-10-819 C alleles and IL-10-592 C alleles was associated with an increased risk for gastric cancer development in H. pylori-infected patients and IL-10 promoter polymorphisms and H. pylori have a synergistic effect on gastric cancer in Hexi population. PMID- 22081334 TI - Risk of obesity and type 2 diabetes with tumor necrosis factor-alpha 308G/A gene polymorphism in metabolic syndrome and coronary artery disease subjects. AB - Tumor Necrosis Factor-alpha (TNF-alpha) has been implicated in the pathogenesis of insulin resistance and obesity. The increased expression of TNF-alpha in adipose tissue is known to induce insulin resistance, and a polymorphism at position -308 in the promoter region of TNF-alpha gene may lead to its increased transcription in adipocytes. The objective of this work was to determine the role of TNFalpha-308G/A gene polymorphism in metabolic syndrome (MetS) and coronary artery disease (CAD) with obesity and type 2 diabetes mellitus (T2DM). A total of 250 MetS and 224 CAD patients and 214 controls were studied. TNFalpha-308G/A polymorphism was detected from the whole blood genomic DNA using PCR amplification refractory mutation system. The 2 * 2 contingency tables and multiple regression analysis were used for determining the association of genotypes with obesity and type 2 diabetes mellitus (T2DM) in MetS and CAD subjects. In CAD subjects with T2DM, the AG genotypes showed a very strong association (P < 0.0001; OR 0.194, 95%CI 0.103-0.365). In CAD subjects with obesity, the AA (P = 0.049; OR 2.449) and AG genotypes showed a strong association (P < 0.0001; OR 0.206). In both males and females, AG genotype and G allele (P < 0.0001) showed a strong association with T2DM. In MetS subjects with T2DM, there was a strong association with AG (P = 0.002; OR 4.483) as well as AA+AG genotypes (P = 0.002; OR 4.255). The AA and AG genotype (P = 0.001; OR 5.497) in males showed a strong 4.6- and 5.4-fold risks, respectively, with obesity. In females, only AG genotype showed a strong 4.5-fold risk with obesity (P = 0.001). In MetS subjects with obesity, the AA genotype (P = 0.043; OR 3.352) as well as AG showed a very strong association (P = 0.001; OR 5.011). The AG genotypes showed a high 3.5-fold risk with T2DM in females (P = 0.011). In CAD subjects, AG genotype showed a protective effect in both obese males and females (P < 0.0001). Heterozygous TNFalpha-308G/A gene variant may be an important risk factor for MetS with T2DM and obesity in both males and females, but may have a protective role in CAD subjects with obesity and T2DM. A allele may be an important risk factor for MetS and CAD with obesity as well as CAD subjects with T2DM. PMID- 22081335 TI - Tumor staging and grading: a primer. AB - Cancer staging and grading are used to predict the clinical behavior of malignancies, establish appropriate therapies, and facilitate exchange of precise information between clinicians. The internationally accepted criteria for cancer staging, the tumor-node-metastasis (TNM) system, includes: (1) tumor size and local growth (T); (2) extent of lymph node metastases (N); and (3) occurrence of distant metastases (M). Clinical stage is established before initiation of therapy and depends on the physical examination, laboratory findings, and imaging studies. Pathologic stage is determined following surgical exploration of disease spread and histological examination of tissue. The TNM classification system has evolved over 50 years to accommodate increasing knowledge about cancer biology. Efforts are ongoing to keep the system both synchronized with the most sophisticated cancer technology and simple for ease of clinician/patient use. Upcoming molecular technologies, such as genomic and proteomic profiling of tumors, microRNA profiling, and even ex vivo living tumor tissue treatment, could improve the current TNM staging system. This chapter describes the current TNM system using breast, lung, ovarian, and prostate cancer examples. PMID- 22081336 TI - Clinical trial design in the age of molecular profiling. AB - The accelerating science of molecular profiling has necessitated a rapid evolution in clinical trial design. Traditional clinical research begins with Phase I studies to characterize dose-limiting toxicities and defines maximally tolerated doses of drugs in small numbers of patients. Traditional Phase II studies test these drugs at the doses discovered during Phase I drug development in small numbers of patients evaluating efficacy and safety. Phase III studies test new therapies to demonstrate improved activity or improved tolerability compared with a standard of care regimen or a placebo. The rapid advances in the understanding of signal transduction, and the identification of new potential diagnostic and therapeutic targets, now require the design and implementation of molecular clinical trials that are very different than traditional Phase I, II, or III trials. The main differentiating factor is the use of a molecular end point to stratify a subset of patients to receive a specific treatment regimen. This chapter focuses on the issues surrounding (a) the definition of clinical end points and the assessment of tumor response; (b) clinical trial design models to define the targeted pathway; and (c) the need for appropriate biomarkers to monitor the response. PMID- 22081337 TI - Personalized medicine: ethics for clinical trials. AB - Modern ethical codes in medicine were developed following World War II to provide respect for persons, beneficence, and justice in clinical research. Clinical trial medicine involves greater scrutiny than most research activities. In every instance, clinical trials have institutional review boards to ensure the medical procedure under study complies with regulatory requirements, privacy, informed consent, good practices, safety monitoring, adverse events reporting, and is free of conflicting interests. Mandatory training in medical ethics for all clinical staff is becoming more common, and at some institutions, knowledgeable patient advocates play a watchdog role. In personalized medicine, each patient becomes a clinical trial of one, based on the uniqueness of the person's illness and the relatively tailored treatment. These features imply a shared responsibility between the patient and the researchers because uncertainty exists over the outcome for each individual patient. This chapter introduces ethical considerations using case studies, with historical context, and describes general ethical guidelines for initiating a clinical trial. PMID- 22081338 TI - Reduction of preanalytical variability in specimen procurement for molecular profiling. AB - Despite the tremendous perceived value, and the predicted high abundance, of disease-associated tissue biomarkers, the number of biomarkers that have been validated for routine clinical use is very low. The major roadblock has been the sample-to-sample variability and perishability of biomolecules in tissue. A chief source of variability is biomolecule perturbation caused by sample handling, the time delays following procurement, and the method of preservation. Living tissue that has been separated from its blood supply during surgical procurement goes through defined stages of reactive changes preceding death, beginning with oxidative, hypoxic, and metabolic stress. These reactive fluctuations in the tissue biomolecules can occur within 20 min postexcision, and can significantly distort the levels of critical diagnostic and prognostic biomolecules. Depending on the delay time ex vivo, and manner of handling, protein biomarkers such as signal pathway phosphoproteins will be elevated or suppressed in a manner that does not represent the biomarker levels at the time of excision. Based on analysis of phosphoproteins, one of the most labile tissue protein biomarkers, we set forth tissue procurement guidelines for clinical research. We further propose the future use of a multipurpose fixative solution designed to stabilize, preserve and maintain proteins, nucleic acids, and tissue architecture. PMID- 22081339 TI - The human side of cancer biobanking. AB - The future success of translational research is critically dependent on the procurement and availability of high-quality tissue specimens linked to accurate histopathologic and clinical information about the individual banked specimen. The international community has awakened to this critical need only recently. Three major roadblocks have hindered the success of previous biobank consortiums: (1) Ethical issues surrounding patient consent and ownership of intellectual property, (2) Failure to properly preserve the molecular content of the tissue, and failure to reliably document clinical data linked to the specimen, and (3) Management issues: inadequate funding, competition for use of the tissue, inadequate personnel and facilities, and absence of dedicated database software. This chapter reviews these critical roadblocks and discusses international efforts to provide strategies to implement high-quality biobanks. PMID- 22081340 TI - Introduction to genomics. AB - The science of genomes: only within the past few decades have scientists progressed from the analysis of a single or a small number of genes at once to the investigation of thousands of genes, going from the study of the units of inheritance to the investigation of the whole genome of an organism. The science of the genomes, or "genomics," initially dedicated to the determination of DNA sequences (the nucleotide order on a given fragment of DNA), has promptly expanded toward a more functional level--studying the expression profiles and the roles of both genes and proteins. The aim of the chapter is to review some basic assumptions and definitions that are the fabric of genomics, and to elucidate key concepts and approaches on which genomics rely. PMID- 22081341 TI - Genomic profiling: cDNA arrays and oligoarrays. AB - The introduction of microarray technology, which is a multiplexed hybridization based process, allows simultaneous analysis of a large number of nucleic acid transcripts. This massively parallel analysis of a cellular genome will become essential for guiding disease diagnosis and molecular profiling of an individual patient's tumor. Nucleic acid based microarrays can be used for: gene expression profiling, single-nucleotide polymorphisms (SNPs) detection, array-comparative genomic hybridizations, comparisons of DNA-methylation status, and microRNA evaluation.A multitude of commercial platforms are available to construct and analyze the microarrays. Typical workflow for a microarray experiment is: preparation of cDNA or gDNA, array construction, hybridization, fluorescent detection, and analysis. Since many sources of variability can affect the outcome of one experiment and there is a multitide of microarray platforms available, microarray standards have been developed to provide industry-wide quality control and information related to each microarray. In this chapter, we review array construction, methodologies, and applications relevant to molecular profiling. PMID- 22081342 TI - Genome-wide methylation profiling in archival formalin-fixed paraffin-embedded tissue samples. AB - New technologies allow for genome-scale measurement of DNA methylation. In an effort to increase the clinical utility of DNA methylation as a biomarker, we have adapted a commercial bisulfite epigenotyping assay for genome-wide methylation profiling in archival formalin-fixed paraffin-embedded pathology specimens. This chapter takes the reader step by step through a biomarker discovery experiment to identify phenotype-correlated DNA methylation signatures in routine pathology specimens. PMID- 22081343 TI - An overview of microRNA methods: expression profiling and target identification. AB - MicroRNAs (miRNAs) are small, single-stranded RNA molecules encoded by genes that are transcribed from DNA but not translated into protein (noncoding RNA). The ability of miRNA to regulate the expression of, as yet, an unknown quantity of targets has recently become an area of huge interest to researchers studying many different areas in many species. Identifying miRNA targets provides functional insights and strategies for therapy. Furthermore, the recent advent of high throughput methods for profiling miRNA expression and for the identification of miRNA targets has ushered in a new era in the research of gene regulation. miRNA profiling further adds a new dimension of information for the molecular profiling of disease. Summarized herein are the methods used to query the expression of miRNAs at both an individual and global level. We have also described modern computational approaches to identifying miRNA target transcripts. PMID- 22081344 TI - Antibody validation by Western blotting. AB - Validation of antibodies is an integral part of translational research, particularly for biomarker discovery. Validation is essential to show the specificity of the reagent (antibody) and to confirm the identity of the protein biomarker, prior to implementing the biomarker in clinical studies.Antibody validation is the procedure in which a single antibody is thoroughly assayed for sensitivity and specificity. Although a plethora of commercial antibodies exist, antibody specificity must be thoroughly demonstrated using a complex biological sample, rather than a recombinant protein, prior to use in clinical translational research. In the simplest iteration, antibody specificity is determined by the presence of a single band in a complex biological sample, at the expected molecular weight, on a western blot.Numerous western blotting procedures are available, spanning the spectrum of single blots to multiplex blots, with images and quantitation generated by manual or automated systems. The basic principles of western blotting are (a) separation of protein mixtures by gel electrophoresis, (b) transfer of the proteins to a blot, (c) probing the blot for a protein or proteins of interest, and (d) subsequent detection of the protein by chemiluminescent, fluorescent, or colorimetric methods. This chapter focuses on the chemiluminescent detection of proteins using a manual western blotting system and a vacuum-enhanced detection system (SNAP i.d.TM, Millipore). PMID- 22081345 TI - Laser capture microdissection: Arcturus(XT) infrared capture and UV cutting methods. AB - Laser capture microdissection (LCM) is a technique that allows the precise procurement of enriched cell populations from a heterogeneous tissue under direct microscopic visualization. LCM can be used to harvest the cells of interest directly or can be used to isolate specific cells by ablating the unwanted cells, resulting in histologically enriched cell populations. The fundamental components of laser microdissection technology are (a) visualization of the cells of interest via microscopy, (b) transfer of laser energy to a thermolabile polymer with either the formation of a polymer-cell composite (capture method) or transfer of laser energy via an ultraviolet laser to photovolatize a region of tissue (cutting method), and (c) removal of cells of interest from the heterogeneous tissue section. Laser energy supplied by LCM instruments can be infrared (810 nm) or ultraviolet (355 nm). Infrared lasers melt thermolabile polymers for cell capture, whereas ultraviolet lasers ablate cells for either removal of unwanted cells or excision of a defined area of cells. LCM technology is applicable to an array of applications including mass spectrometry, DNA genotyping and loss-of-heterozygosity analysis, RNA transcript profiling, cDNA library generation, proteomics discovery, and signal kinase pathway profiling. This chapter describes the unique features of the Arcturus(XT) laser capture microdissection instrument, which incorporates both infrared capture and ultraviolet cutting technology in one instrument, using a proteomic downstream assay as a model. PMID- 22081346 TI - Antibody microarrays: analysis of cystic fibrosis. AB - Cystic fibrosis (CF) is the most common autosomal recessive disease in the USA and Europe, whose life-limiting phenotype is manifest on epithelial cells throughout the body. The principal cause of morbidity and mortality is a massively proinflammatory condition in the lung. The mutation responsible for most cases of CF is [DeltaF508]CFTR. However, the penetrance of the disease is quite variable, and adverse events leading to hospitalization cannot be easily predicted. Thus, there is a strong need for prognostic endpoints that might serve to identify impending clinical problems long before they happen. Our approach has been to search for proteomic signatures in easily accessed biological fluids that might identify the molecular basis for adverse events. We describe here a workflow that begins with patient-derived bronchial brush biopsies and progresses to analysis of serum and plasma from patients on antibody microarrays. PMID- 22081347 TI - Tissue microarrays as a tool in the discovery and validation of predictive biomarkers. AB - The tissue microarray (TMA) is the embodiment of high-throughput pathology. The platform combines tens to hundreds of tissue samples on a single microscope slide for interrogation with routine molecular pathology tools. TMAs have enabled the rapid and cost-effective screening of biomarkers for diagnostic, prognostic, and predictive utility. Most commonly applied to the field of oncology, the TMA has accelerated the development of new biomarkers, and is emerging as an essential tool in the discovery and validation of tissue biomarkers for use in personalized medicine. This chapter provides an overview of TMA technology and highlights the advantages of using TMAs as tools toward rapid introduction of new biomarkers for clinical use. PMID- 22081348 TI - Reverse-phase protein microarrays. AB - Cancer is the consequence of intra- and extracellular signaling network deregulation that derives from alteration of genetic and proteomic cellular homeostasis. Mapping the individual molecular circuitry of a patient's tumor cells is the starting point for rational personalized therapy.While genes and RNA encode information about cellular status, proteins are considered the engine of the cellular machine, as they are the effective elements that drive cellular functions, such as proliferation, migration, differentiation, and apoptosis. Consequently, investigations of the cellular protein network are considered a fundamental tool to understand cellular functions. In the last decades, increasing interest has been focused on the improvement of new technologies for proteomic analysis. In this context, reverse-phase protein microarrays (RPMAs) have been developed to study and analyze posttranslational modifications that are responsible for principal cell functions and activities. This innovative technology allows the investigation of protein activation as a consequence of protein-protein interaction or biochemical reactions, such as phosphorylation, glycosylation, ubiquitination, protein cleavage, and conformational alterations.Intracellular balance is carefully conserved by constant rearrangements of proteins through the activity of a series of kinases and phosphatases. Therefore, knowledge of the key cellular signaling cascades reveal information regarding the cellular processes driving a tumor's growth (such as cellular survival, proliferation, invasion, and cell death) and response to treatment.Alteration to cellular homeostasis, driven by elaborate intra- and extracellular interactions, has become one of the most studied fields in the era of personalized medicine and targeted therapy. RPMA technology is a valid tool that can be applied to protein analysis of several diseases for the potential to generate protein interaction and activation maps that lead to the identification of critical nodes for individualized or combinatorial target therapy. PMID- 22081349 TI - Serum low-molecular-weight protein fractionation for biomarker discovery. AB - Protein biomarkers provide the key diagnostic information for the detection of disease, risk of disease progression, and a patient's likely response to drug therapy. Potential biomarkers exist in biofluids, such as serum, urine, and cerebrospinal fluid. Unfortunately, discovering and validating protein biomarkers are hindered by the presence of high-molecular-weight proteins, such as serum albumin and immunoglobulins, which comprise 90% of the proteins present in these samples. High-abundance, high-molecular-weight proteins mask the low-molecular weight (LMW) proteins and peptides using conventional protein detection methods. Candidate biomarkers are believed to exist in very low concentrations and comprise less than 1% of serum proteins, and may be highly labile as well. Therefore, it is imperative to isolate and enrich LMW proteins from complex mixtures for biomarker discovery. This chapter describes a continuous -elution electrophoresis method, based on molecular weight sieving, to isolate specific molecular weight fractions for mass spectrometric, western blotting, or protein array analysis. PMID- 22081350 TI - Mass spectrometry-based biomarker discovery. AB - Discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomic is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues of interest or body fluids with subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. The aim of our chapter is to provide practical lab procedures for sample digestion and protein fractionation for subsequent mass spectrometry analysis. PMID- 22081351 TI - Mitochondrial proteome: toward the detection and profiling of disease associated alterations. AB - Existing at the heart of cellular energy metabolism, the mitochondrion is uniquely positioned to have a major impact on human disease processes. Examples of mitochondrial impact on human pathology abound and include etiologies ranging from inborn errors of metabolism to the site of activity of a variety of toxic compounds. In this review, the unique aspects of the mechanisms related to the mitochondrial proteome are discussed along with an overview of the literature related to mitochondrial proteomic exploration. The review includes discussion of potential areas for exploration and advantages of applying proteomic techniques to the study of mitochondria. PMID- 22081352 TI - Adult neural stem cells: isolation and propagation. AB - Individualized therapy using adult stem cells constitutes a revolutionary vision for molecular medicine of the future. The field of stem cell biology has accelerated dramatically such that it now appears feasible to treat an individual patient's disease with native or modified stem cells collected from the same patient. Neurodegenerative disease is a high-priority goal for stem cell therapy due to the tremendous clinical urgency to reduce the worldwide suffering associated with this class of diseases. This chapter focuses on adult neural stem cells as a prototype for the general field of adult stem cell therapy. Studies of the origin and function of neural stem cells reveals that the adult brain can generate new neurons. This finding provides the rationale for the therapeutic application of adult neural stem cells to treat neuronal damage or loss. Experimental progress in treating Parkinson's disease is discussed in some detail as an example of one of the most promising areas for adult neural stem cell therapy. Methods for neural stem cell isolation and propagation are included. PMID- 22081353 TI - Evanescent-wave field imaging: an introduction to total internal reflection fluorescence microscopy. AB - Advancements in technology and computational power in recent years have directly impacted modern microscopy through improvements in light detection, imaging software platforms, as well as integration of complex hardware systems. These successes have allowed for mainstream utilization of previously complex microscopic techniques such as total internal reflection fluorescence (TIRF) microscopy, revealing many aspects of cell biology not previously appreciated. Through the restriction of illumination to areas of cell-coverslip interfaces in combination with modern detectors, TIRF microscopy allows researchers in the life sciences a glimpse of dynamic cellular phenomena with resolutions never before achieved.This chapter provides a basic overview to the concept of TIRF microscopy and some considerations to setting up this technique in the lab. PMID- 22081354 TI - Construction and hyperspectral imaging of quantum dot lysate arrays. AB - The emerging field of proteomic molecular profiling will be driven by new technologies that can measure dozens to hundreds of proteins from a small sample input from a patient's biopsy. Lysate arrays, or reverse-phase protein microarrays, provide a platform for complex mixtures of proteins extracted from cells and tissues to be directly immobilized onto a solid support (such as a biochip with protein binding capacity) in diminutive volumes (picoliter-to nanoliter). The proteins are spotted using precision robotics and then quantitatively assayed using primary antibodies; important posttranslational modifications, such as phosphorylations that are important for protein activation, may also be assayed to provide an estimate of the regulation of cellular signaling. Until recently, chromogenic signals and fluorescence (using organic fluorophores) detection were two strategies relied upon for signal detection. Emerging regents such as quantum dots (Qdot(r) nanocrystals; QD) are now employed for improved performance. QD embody a more versatile detection system because the robust signals may be time averaged and the narrow spectral emissions enable many protein targets to be quantified within the same lysate spot. Previously, we found that commercially available pegylated, streptavidin conjugated QD were effective detection agents, with low-background affinities to spurious components within heterogeneous protein mixtures. Hyperspectral imaging allows the simultaneous detection of the different colored QD reagents within a single lysate spot. Here, we described the construction and imaging of QD lysate arrays. This technology is an emerging, enabling tool within the exciting, clinically oriented field of clinical tissue proteomics. PMID- 22081355 TI - Microarray data analysis: comparing two population means. AB - Scientists employing microarray profiling technology to compare sample sets generate data for a large number of endpoints. Assuming the experimental design minimized sources of bias, and the analytical technology was reliable, precise, and accurate, how does the experimentalist determine which endpoints are meaningfully different between the groups? Comparison of two population means for individual analysis measurements is the most common statistical problem associated with microarray data analysis. This chapter focuses on the hands-on procedures using SAS software to describe how to choose statistical methods to find the statistically significantly different endpoints between two groups of data generated from reverse phase protein microarrays. The four methods outlined are: (a) two-sample t-test, (b) Wilcoxon rank sum test, (c) one-sample t-test, and (d) Wilcoxon signed rank test. Two sample t-test is used for two independently normally distributed groups. One-sample t-test is used for a normally distributed difference of paired observations. Wilcoxon rank sum test is considered a nonparametric version of the two-sample t-test, and Wilcoxon signed rank test is considered a nonparametric version of the one-sample t-test. PMID- 22081356 TI - Bioinformatics/biostatistics: microarray analysis. AB - The quantity and complexity of the molecular-level data generated in both research and clinical settings require the use of sophisticated, powerful computational interpretation techniques. It is for this reason that bioinformatic analysis of complex molecular profiling data has become a fundamental technology in the development of personalized medicine. This chapter provides a high-level overview of the field of bioinformatics and outlines several, classic bioinformatic approaches. The highlighted approaches can be aptly applied to nearly any sort of high-dimensional genomic, proteomic, or metabolomic experiments. Reviewed technologies in this chapter include traditional clustering analysis, the Gene Expression Dynamics Inspector (GEDI), GoMiner (GoMiner), Gene Set Enrichment Analysis (GSEA), and the Learner of Functional Enrichment (LeFE). PMID- 22081357 TI - Structure-based functional design of drugs: from target to lead compound. AB - Proteomic and genomic discoveries have identified vast numbers of new drug targets for investigation. In the quest to discover drugs that modulate the function of these targets, identification of small-molecule drug leads is one of the earliest steps. Structure-based drug design has emerged as a valuable, inexpensive, and rapid computational resource that identifies lead compounds that are complementary to the structure of the target. Leads identified through this process are biologically evaluated and "hit compounds" with affinity and activity are further optimized. This chapter introduces the process of structure-based drug design, including preparation of the ligand database, preparation of the target structure, docking and scoring, and evaluation. PMID- 22081358 TI - Personalized medicine: changing the paradigm of drug development. AB - Despite an increased investment in research and development, there has been a steady decline in the number of drugs brought to market over the past 40 years. The tools of personalized medicine are refining diseases into molecular categories, and future therapeutics may be dictated by a patient's molecular profile relative to these categories. The adoption of a personalized medicine approach to drug development may improve the success rate by minimizing variability during each phase of the drug development process. This chapter describes the current paradigm of drug development and then discusses how molecular profiling/personalized medicine might be used to improve upon this paradigm. PMID- 22081359 TI - Grant writing tips for translational research. AB - All investigators face the same challenge - the highly competitive nature of the grant review process. Innovation alone is not enough to ensure grant supported funding. Applied clinical research requires a diverse collaborative team of investigators with specialized skills, a supportive clinical research environment, and access to clinical material. In addition, ethical limitations, and lack of animal models for many diseases, prevent direct mechanistic experiments that are possible using in vitro systems or animal models. Therefore, specific granting mechanisms and program initiatives target translational research studies. This chapter provides grant writing tips and lists resources that may prove helpful for new investigators seeking research funding in support of translational research, biobanking, and research utilizing molecular biomarkers. PMID- 22081360 TI - Inventions and patents: a practical tutorial. AB - Patents are designed to protect and encourage creativity and innovation. Patenting a biomedical discovery can be a requirement before a pharmaceutical company or biotech entity will invest in the lengthy and costly clinical testing necessary to achieve patient benefit. Although scientists and clinicians are well versed in research publication requirements, patent descriptions and claims are formatted in a manner quite different from a research paper. Patents require (a) a series of logical statements clearly delineating the boundaries of the novel aspects of the invention and (b) sufficient disclosure of the invention so that it can be reproduced by others. Patents are granted only for inventions that meet three conditions: novelty, nonobviousness, and usefulness. This chapter provides basic guidelines and definitions of technology transfer: inventions, inventorship, and patent filing, which are summarized using a question and answer format. PMID- 22081361 TI - Regulatory approval pathways for molecular diagnostic technology. AB - This chapter describes the basic categories for regulatory approval to sell/market a molecular profiling technology. The US Food and Drug Administration regulates and provides guidance, for marketing in vitro diagnostic devices (IVD). Three different paths currently exist for obtaining Food and Drug Administration (FDA) approval of an IVD: (a) If the new test can be shown to be substantially equivalent to an existing predicate test on the market, then the 510(k) is the regulatory path for new device approval. (b) If your new diagnostic technology cannot be considered substantially equivalent to an existing technology, and will be used to make a critical medical decision concerning the diagnosis, treatment, or medical management, then the premarket approval (PMA) is the regulatory path of choice. (c) If no predicate device exists and the test is of low or moderate risk, it may be eligible for a de novo reclassification. If the test is done "in house," in the designated laboratory only, for a patient sample that is sent to the laboratory from an outside physician's office or medical facility, then the test can be potentially marketed under "home brew" guidelines (also known as laboratory developed tests) regulated under the Clinical Laboratory Improvement Amendments (CLIA). The Centers for Medicare and Medicaid Services (CMS) assumes primary responsibility for financial management operations of the CLIA program, but the categorization of commercially marketed in vitro diagnostic tests under CLIA is the responsibility of the FDA. Definitions, guidelines, information sources, and instructions for data requirements are outlined for each regulatory pathway. PMID- 22081362 TI - Small business development for molecular diagnostics. AB - Molecular profiling, which is the application of molecular diagnostics technology to tissue and blood -specimens, is an integral element in the new era of molecular medicine and individualized therapy. Molecular diagnostics is a fertile ground for small business development because it can generate products that meet immediate demands in the health-care sector: (a) Detection of disease risk, or early-stage disease, with a higher specificity and sensitivity compared to previous testing methods, and (b) "Companion diagnostics" for stratifying patients to receive a treatment choice optimized to their individual disease. This chapter reviews the promise and challenges of business development in this field. Guidelines are provided for the creation of a business model and the generation of a marketing plan around a candidate molecular diagnostic product. Steps to commercialization are outlined using existing molecular diagnostics companies as learning examples. PMID- 22081363 TI - Recent progress in treatment of pulmonary arterial hypertension due to congenital heart disease. PMID- 22081364 TI - Rosuvastatin blocks hERG current and prolongs cardiac repolarization. AB - Blocking of the potassium current I(Kr) [human ether-a-go-go related gene (hERG)] is generally associated with an increased risk of long QT syndrome (LQTS). The 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, rosuvastatin, is a methanesulfonamide derivative, which shows structural similarities with several I(Kr) blockers. Hence, we assessed the effects of rosuvastatin on cardiac repolarization by using in vitro, ex vivo, and in vivo models. Patch clamp experiments on hERG-transfected human embryonic kidney (HEK) 293 cells established the potency of rosuvastatin to block hERG [half maximal inhibitory concentration (IC(50) ) = 195 nM]. We showed in isolated guinea pig hearts that 195 nM rosuvastatin prolonged (basic cycle length of 250 ms; p < 0.05) the monophasic action potential duration at 90% repolarization (MAPD(90) ) by 11 +/- 1 ms. Finally, rosuvastatin (10 mg/kg, intraperitoneal) prolonged corrected QT interval (QTc) in conscious and unrestrained guinea pigs from 201 +/- 1 to 210 +/ 2 ms (p < 0.05). Thus, rosuvastatin blocks I(Kr) and prolongs cardiac repolarization. In additional experiments, we also show that hERG blockade in HEK 293 cells was modulated by coexpression of efflux [breast cancer resistance protein (BCRP), multidrug resistance gene (MDR1)] and influx [organic anion transporting polypeptide (OATP) 2B1] transporters involved in the disposition and cardiac distribution of the drug. Genetic polymorphisms observed for BCRP, MDR1, and OATP2B1, and IC(50) determined for hERG blocking lead us to propose that some patients may be at risk of rosuvastatin-induced LQTS. PMID- 22081365 TI - Measuring pain impact versus pain severity using a numeric rating scale. AB - BACKGROUND: Routine assessments of pain using an intensity numeric rating scale (NRS) have improved documentation, but have not improved clinical outcomes. This may be, in part, due to the failure of the NRS to adequately predict patients' preferences for additional treatment. OBJECTIVE: To examine whether patients' illness perceptions have a stronger association with patient treatment preferences than the pain intensity NRS. DESIGN: Single face-to-face interview. PARTICIPANTS: Outpatients with chronic, noncancer, musculoskeletal pain. MAIN MEASURES: Experience of pain was measured using 18 illness perception items. Factor analysis of these items found that five factors accounted for 67.1% of the variance; 38% of the variance was accounted for by a single factor labeled "pain impact." Generalized linear models were used to examine how NRS scores and physical function compare with pain impact in predicting preferences for highly effective/high-risk treatment. KEY RESULTS: Two hundred forty-nine subjects agreed to participate. Neither NRS nor functioning predicted patient preference (NRS: chi2 = 1.92, df = 1, p = 0.16, physical functioning: chi2 = 2.48, df = 1, p = 0.11). In contrast, pain impact was significantly associated with the preference for a riskier/more effective treatment after adjusting for age, comorbidity, efficacy of current medications and numeracy (chi2 = 4.40, df = 1, p = 0.04). CONCLUSIONS: Tools that measure the impact of pain may be a more valuable screening instrument than the NRS. Further research is now needed to determine if measuring the impact of pain in clinical practice is more effective at triggering appropriate management than more restricted measures of pain such as the NRS. PMID- 22081366 TI - Genetic characterization of Escherichia coli O157:H7 strains isolated from the one-humped camel (Camelus dromedarius) by using microarray DNA technology. AB - From the Camelidae family members, several serotypes of Escherichia coli (E. coli) have recently been isolated from diarrhoeic and non-diarrhoeic faecal samples. To date Shiga toxin-producing E. coli (STEC) strains have never been typed in one-humped camel (Camelus dromedarius). In the present study, two E. coli O157:H7 strains isolated from sick dromedaries were investigated. Virulence gene profiles were determined using a custom E. coli virulence DNA microarray, composed of 70-mer oligonucleotide probes targeting 264 virulence or related genes of known E. coli pathotypes. Both strains displayed positive hybridization signals for the Locus of enterocyte effacement (LEE) gene probes (ler, eae, espA, espB, tir genes), two Shiga toxin probes (stx1 and stx2), the O157 O-antigen specific probe, various virulence plasmid (pO157) probes like katP in addition to other accessory virulence genes characterized in STEC. PMID- 22081367 TI - Effectiveness of AFLPs and retrotransposon-based markers for the identification of Portuguese grapevine cultivars and clones. AB - Grapevine germplasm, including 38 of the main Portuguese cultivars and three foreign cultivars, Pinot Noir, Pinot Blanc and Chasselas, used as a reference, and 37 true-to-type clones from the Alvarinho, Arinto, Loureiro, Moscatel Galego Branco, Trajadura and Vinhao cultivars were studied using AFLP and three retrotransposon-based molecular techniques, IRAP, REMAP and SSAP. To study the retrotransposon-based polymorphisms, 18 primers based on the LTR sequences of Tvv1, Gret1 and Vine-1 were used. In the analysis of 41 cultivars, 517 IRAP, REMAP, AFLP and SSAP fragments were obtained, 83% of which were polymorphic. For IRAP, only the Tvv1Fa primer amplified DNA fragments. In the REMAP analysis, the Tvv1Fa-Ms14 primer combination only produced polymorphic bands, and the Vine-1 primers produced mainly ISSR fragments. The highest number of polymorphic fragments was found for AFLP. Both AFLP and SSAP showed a greater capacity for identifying clones, resulting in 15 and 9 clones identified, respectively. Together, all of the techniques allowed for the identification of 54% of the studied clones, which is an important step in solving one of the challenges that viticulture currently faces. PMID- 22081368 TI - Promise of factor Xa inhibition in acute coronary syndromes. AB - Drugs that inhibit factor Xa have been shown to reduce mortality and morbidity in acute coronary syndromes (ACS). Presently, factor Xa inhibition is most often achieved indirectly with the heparins and, increasingly, fondaparinux. Despite effective anticoagulation with indirect factor Xa inhibition there remains considerable mortality and morbidity in ACS. The recently developed direct factor Xa inhibitors (the xabans) appear to offer promise as alternatives to the heparins. We review the evidence behind indirect and direct factor Xa inhibition in non-ST-segment elevation ACS, ST-segment elevation myocardial infarction, and with percutaneous coronary intervention. PMID- 22081369 TI - Recent trends of the emission characteristics from the road construction industry. PMID- 22081370 TI - Chemometric evaluation for the relation of BCR sequential extraction method and in vitro gastro-intestinal method for the assessment of metal bioavailability in contaminated soils in Turkey. AB - INTRODUCTION: A chemometric evaluation has been done to classify metal ions in soils and to determine whether or not the gastric and intestinal phases of a physiologically based extraction test bear any relation to any of the phases of the four-stage Community Bureau of Reference (BCR) extraction protocol. MATERIALS AND METHODS: Nine trace analytes (As, Ba, Cd, Cr, Cu, Mn, Ni, Pb and Zn) were determined in extracts obtained from the BCR sequential extraction procedure as well as from in vitro gastro-intestinal experiments. The results showed that high As, Pb, Zn and Cd concentrations were found in these soils. Principal component analysis (PCA) and linear discriminant analysis were used as classification techniques. Stepwise multiple linear regression analysis was applied to the data set to determine how the bioaccessibility of a metal is linked to the operationally defined fractions of metal speciation in soil. RESULTS AND DISCUSSION: This analysis showed that the metal concentrations in the intestinal and gastric extracts are mainly dependent on the concentrations found in BCR phases 1 and 2 for each metal ion except for Cr, which was mainly dependent on the concentrations found in BCR phase 3. From the chemometric technique of correlation analysis, it was concluded that the metals extracted using BCR phases 1 and 2 are more likely to be bioaccessible, i.e. are also extracted by gastric and intestinal digestion solutions. When the correlation and PCA results were interpreted together, it indicated that the bioaccessiblity of Zn, Pb, Mn and Cd were higher than As, Ba, Cr, Ni and Cu for these soils. PMID- 22081371 TI - Use of inorganic and organic wastes for in situ immobilisation of Pb and Zn in a contaminated alkaline soil. AB - PURPOSE: This study aims to examine whether addition of immobilising agents to a sandy, alkaline (pH = 8.1) soil, which had been contaminated with Pb and Zn by airborne particles from a Pb/Zn smelter, would substantially reduce metal bioavailability. METHODS: The effectiveness of five waste materials (blast furnace (BF) slag, alum water treatment (WT) sludge, red mud, sugar mill mud and green waste compost) as metal immobilising agents was evaluated by incubating them with a contaminated soil for a period of 12 months at rates of 5% and 10% (w/w), after which, Rhodes grass was grown in the soils in a greenhouse study. RESULTS: Additions of WT sludge, BF slag and red mud reduced CaCl(2), CH(3)COOH, HCl and EDTA-extractable Zn but compost and mill mud had no appreciable immobilising effects. Additions of all amendments reduced levels of CaCl(2), CH(3)COOH and HCl-extractable Pb although concentrations of EDTA-extractable Pb remained unchanged. A sequential extraction procedure showed that additions of mill mud and compost increased the percentage of total Pb and Zn present in the oxidisable fraction whilst additions of the other materials increased the percentage present in the residual fraction. Rhodes grass yields were promoted greatly by additions of red mud, compost and particularly mill mud, and yields were negatively correlated with tissue Pb concentrations and extractable Pb. CONCLUSIONS: Red mud was the most effective material for lowering extractable Pb and Zn levels simultaneously while mill mud and compost were notably effective for Pb. A field evaluation in the study area is justified. PMID- 22081372 TI - Bacterial community profiles from sediments of the Anacostia River using metabolic and molecular analyses. AB - BACKGROUND AIM AND SCOPE: Though the tidal Anacostia River, a highly polluted riverine system, has been well characterized with regard to contaminants, its overall resident bacterial populations have remained largely unknown. Improving the health of this system will rely upon enhanced understanding of the diversity and functions of these communities. Bacterial DNA was extracted from archived (AR, year 2000) and fresh sediments (RE, year 2006) collected from various locations within the Anacostia River. Using a combination of metabolic and molecular techniques, community snapshots of sediment bacterial diversity and activity were produced. RESULTS: Employing Biolog EcoPlates, metabolic analysis of RE sediments from July revealed similar utilization of amines, amino acids, carbohydrates, carboxylic acids, and polymers at all sites. Normalized optical density measurements demonstrated that for most compounds, utilizations were similar though when differences did occur, the downstream site was enhanced compared to one or both of the upstream sites. Using denaturing gradient gel electrophoresis, bacterial diversity fingerprints of operational taxonomic units (OTUs) were obtained. Dendograms of the banding patterns revealed qualitative relationships as well as differences between replicate samples from similar sites. Replicates from the AR sites shared several common OTUs, while RE sites were more varied. Species richness and Shannon diversity indices generally increased with increasingly downstream locations, and were significant for the AR sediments (analysis of variance, P < 0.0001). Carbon and nitrogen content and concentration of fine grain sediment (<63 MUm) were positively correlated with OTU richness (r (2) = 0.37, P = 0.0008; r (2) = 0.45, P < 0.0001; r (2) = 0.48, P = 0.001, respectively). CONCLUSIONS: This study demonstrated that the bacterial communities from all regions sampled were not only metabolically active with the capacity to utilize several different compounds as energy sources but also were genetically diverse. This study is the first to focus on the overall bacterial community, providing insight into this vital component of stream ecosystems. Understanding the bacterial components of aquatic systems such as the Anacostia River will increase our knowledge of the overall structure and function of the ecological communities in polluted systems, subsequently enhancing our ability to improve the health of this important tidal river. PMID- 22081373 TI - Lentivirus-delivered Kruppel-like factor 8 small interfering RNA inhibits gastric cancer cell growth in vitro and in vivo. AB - We found that the transcription factor Kruppel-like factor 8 (KLF8) was highly expressed in gastric cancer tissues and cell lines compared with adjacent noncancerous regions and gastric epithelial mucosa cells. We employed a lentivirus-mediated RNAi technique to knockdown KLF8 expression in gastric cancer cell line SGC7901 and observed its effects on cell growth in vitro and in vivo. Knockdown of KLF8 inhibited SGC7901 cell proliferation, promoted cell apoptosis, inhibited the tumorigenicity of SGC7901 cells, and significantly decreased tumor growth when the cells were injected into nude mice. These results indicated that overexpression of KLF8 may influence the biological behavior of SGC7901 gastric cancer cells. Knockdown of KLF8 expression by lentivirus-delivered siRNA may be useful as a therapeutic agent for the treatment of gastric cancer. PMID- 22081374 TI - Reduced expression of DNA repair genes (XRCC1, XPD, and OGG1) in squamous cell carcinoma of head and neck in North India. AB - Squamous cell carcinoma of head and neck (SCCHN) is the sixth most common cancer globally, and in India, it accounts for 30% of all cancer cases. Epidemiological studies have shown a positive association between defective DNA repair capacity and SCCHN. The underlying mechanism of their involvement is not well understood. In the present study, we have analyzed the relationship between SCCHN and the expression of DNA repair genes namely X-ray repair cross-complementing group 1 (XRCC1), xeroderma pigmentosum group D (XPD), and 8-oxoguanine DNA glycosylase (OGG1) in 75 SCCHN cases and equal number of matched healthy controls. Additionally, levels of DNA adduct [8-hydroxyguanine (8-OHdG)] in 45 SCCHN cases and 45 healthy controls were also determined, to ascertain a link between mRNA expression of these three genes and DNA adducts. The relative expression of XRCC1, XPD, and OGG1 in head and neck cancer patients was found to be significantly low as compared to controls. The percent difference of mean relative expression between cases and controls demonstrated maximum lowering in OGG1 (47.3%) > XPD (30.7%) > XRCC1 (25.2%). A negative Spearmen correlation between XRCC1 vs. 8-OHdG in cases was observed. In multivariate logistic regression analysis (adjusting for age, gender, smoking status, and alcohol use), low expression of XRCC1, XPD, and OGG1 was associated with a statistically significant increased risk of SCCHN [crude odds ratios (ORs) (95%CI) OR 2.10; (1.06-4.17), OR 2.76; (1.39-5.49), and 5.24 (2.38-11.52), respectively]. In conclusion, our study demonstrated that reduced expression of XRCC1, XPD, and OGG1 is associated with more than twofold increased risk in SCCHN. PMID- 22081375 TI - Altered expression of circadian clock genes in head and neck squamous cell carcinoma. AB - Head and neck squamous cell carcinoma (HNSCC) means a group of cancers developed from the upper aerodigestive tract, and 90% of them are squamous cell carcinomas. HNSCC is the tenth most commonly diagnosed form of cancer in males worldwide, but it is the seventh most common cause of cancer-related death. The circadian clock regulates daily rhythmic variations in various physiologic processes including sleep and activity, appetite, hormone levels, metabolism, and gene expression. Many recent studies have demonstrated that the disruption of circadian rhythm is associated with cancer development and tumor progression, such as chronic myeloid leukemia, hepatocellular carcinoma, endometrial carcinoma, and breast cancer. However the direct links between aberrant circadian clock gene expression and human malignancies, including HNSCC, remain largely unknown. In this study, the expression profiles of nine circadian clock genes of cancer tissue and noncancerous part from 40 patients of HNSCC were investigated. The expression of PER1, PER2, PER3, CRY1, CRY2, CKIepsilon, and BMAL1 showed significant downregulation in the cancer tissues (p < 0.005). Downregulated PER3, CRY2, and BMAL1 expression was correlated with more advanced cancer stages (p < 0.05). Downregulated PER3 and upregulated TIM expression correlated with larger tumor size (p < 0.05), and lower expression of PER3 correlated with deeper tumor invasion (p < 0.05). Poor survival was related to lower expression of PER1 (p < 0.05) and PER3 (p < 0.01). These results indicate a possible association of circadian clock gene, especially PER3, expression with the pathogenesis of HNSCC. PMID- 22081376 TI - COX-2 and survivin reduction may play a role in berberine-induced apoptosis in human ductal breast epithelial tumor cell line. AB - Berberine is an isoquinoline alkaloid that has several pharmacological effects such as antiinflammatory, antimicrobial, apoptosis-inducing and anticancer effects. It has been illustrated that the antiinflammatory effect is mediated by suppressing the nuclear factor-kappa B (NF-kappaB) that activates expression of some antiinflammatory and antiapoptotic proteins including cyclooxygenase-2(COX 2), inducible nitric oxide synthase (iNOS) and survivin; therefore, berberine may induce apoptosis by reducing antiinflammatory and antiapoptotic agents, which suggest the relationship between antiinflammatory and apoptosis pathways. For further illustration of the mechanism of berberine action, the human ductal breast epithelial tumor cell line (T47D cell line) was treated with different concentrations of berberine (25-100 MUM/ml). Berberine in 50 MUM/ml had the most reducing effect on cell viability and inducing of apoptosis. The level of COX-2, iNOS and survivin proteins decreased in berberine-treated cells; however, treatment of the cells with aspirin and aminoguanidine (AG), COX-2 and iNOS inhibitors, respectively, showed that despite the cell growth-reducing effect of aspirin, AG did not have a significant effect on cell viability. On the other hand, with the attention to reduction in survivin protein level in berberine treated cells, the results suggest that the apoptotic effect of berberine may be mediated by reduction in both of the COX-2 and survivin in T47D cell line, while the iNOS does not play any effective role in berberine-induced apoptosis. PMID- 22081377 TI - Is severe sepsis associated with new-onset atrial fibrillation and stroke? PMID- 22081379 TI - Cost function analysis for solid waste management: a developing country experience. AB - The need for improved cost planning methods for solid waste management (SWM) is particularly strong in emerging economies where problems are severe, expectations for improvements are high, but finances are constrained. Estimating cost functions is suggested as an improved cost planning method. The research uses 1999 data from 298 Indian municipalities, covering over 140 million people. Stepwise multiple regression involving eight predictor variables was conducted on costs to detect any statistically significant correlations. The average costs on either a per tonne or per capita basis are most influenced by the total number of staff employed per capita or per tonne. The results are believed to be due to labour costs being such a high fraction of total costs in developing countries. Due to high variability in labour intensity between municipalities the data showed no clear correlation between per tonne or per capita costs and population, indicating no economy-of-scale. The data used here are subject to significant conjecture over their quality and age; however, the unique nature of the study should help future researchers investigating costs in emerging economies. PMID- 22081378 TI - Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis. AB - CONTEXT: New-onset atrial fibrillation (AF) has been reported in 6% to 20% of patients with severe sepsis. Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in the setting of severe sepsis is uncertain. OBJECTIVE: To determine the in-hospital stroke and in hospital mortality risks associated with new-onset AF in patients with severe sepsis. DESIGN AND SETTING: Retrospective population-based cohort of California State Inpatient Database administrative claims data from nonfederal acute care hospitals for January 1 through December 31, 2007. PATIENTS: Data were available for 3,144,787 hospitalized adults. Severe sepsis (n = 49,082 [1.56%]) was defined by validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 995.92. New-onset AF was defined as AF that occurred during the hospital stay, after excluding AF cases present at admission. MAIN OUTCOME MEASURES: A priori outcome measures were in-hospital ischemic stroke (ICD 9-CM codes 433, 434, or 436) and mortality. RESULTS: Patients with severe sepsis were a mean age of 69 (SD, 16) years and 48% were women. New-onset AF occurred in 5.9% of patients with severe sepsis vs 0.65% of patients without severe sepsis (multivariable-adjusted odds ratio [OR], 6.82; 95% CI, 6.54-7.11; P < .001). Severe sepsis was present in 14% of all new-onset AF in hospitalized adults. Compared with severe sepsis patients without new-onset AF, patients with new onset AF during severe sepsis had greater risks of in-hospital stroke (75/2896 [2.6%] vs 306/46,186 [0.6%] strokes; adjusted OR, 2.70; 95% CI, 2.05-3.57; P < .001) and in-hospital mortality (1629 [56%] vs 18,027 [39%] deaths; adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P < .001). Findings were robust across 2 definitions of severe sepsis, multiple methods of addressing confounding, and multiple sensitivity analyses. CONCLUSION: Among patients with severe sepsis, patients with new-onset AF were at increased risk of in-hospital stroke and death compared with patients with no AF and patients with preexisting AF. PMID- 22081380 TI - Assessment of pharmaceutical waste management at selected hospitals and homes in Ghana. AB - The practice of use and disposal of waste from pharmaceuticals compromises the safety of the environment as well as representing a serious health risk, as they may accumulate and stay active for a long time in the aquatic environment. This article therefore presents the outcome of a study on pharmaceutical waste management practices at homes and hospitals in Ghana. The study was conducted at five healthcare institutions randomly selected in Ghana, namely two teaching hospitals (hospital A, hospital B), one regional hospital (hospital C), one district hospital (hospital D) and one quasi-governmental hospital (hospital E). Apart from hospital E which currently has a pharmaceutical waste separation programmr as well as drug return programme called DUMP (Disposal of Unused Medicines Program), all other hospitals visited do not have any separate collection and disposal programme for pharmaceutical waste. A survey was also carried out among the general public, involving the questioning of randomly selected participants in order to investigate the household disposal of unused and expired pharmaceuticals. The results from the survey showed that more than half of the respondents confirmed having unused, left-over or expired medicines at home and over 75% disposed of pharmaceutical waste through the normal waste bins which end up in the landfills or dump sites. PMID- 22081381 TI - Measuring the efficiency of a healthcare waste management system in Serbia with data envelopment analysis. AB - In 2007, the Serbian Ministry of Health initiated specific activities towards establishing a workable model based on the existing administrative framework, which corresponds to the needs of healthcare waste management throughout Serbia. The objective of this research was to identify the reforms carried out and their outcomes by estimating the efficiencies of a sample of 35 healthcare facilities engaged in the process of collection and treatment of healthcare waste, using data envelopment analysis. Twenty-one (60%) of the 35 healthcare facilities analysed were found to be technically inefficient, with an average level of inefficiency of 13%. This fact indicates deficiencies in the process of collection and treatment of healthcare waste and the information obtained and presented in this paper could be used for further improvement and development of healthcare waste management in Serbia. PMID- 22081382 TI - The effect of kaolin on the combustion of demolition wood under well-controlled conditions. AB - In an attempt to look at means for reduction of corrosion in boilers, combustion experiments are performed on demolition wood with kaolin as additive. The experiments were performed in a multi-fuel reactor with continuous feed of pellets and by applying staged air combustion. A total characterization of the elemental composition of the fuel, the bottom ash and some particle size stages of fly ash was performed. This was done in order to follow the fate of some of the problematic compounds in demolition wood as a function of kaolin addition and other combustion-related parameters. In particular chlorine and potassium distribution between the gas phase, the bottom ash and the fly ash is reported as a function of increased kaolin addition, reactor temperature and air staging. Kaolin addition of 5 and 10% were found to give the least aerosol load in the fly ash. In addition, the chlorine concentration in aerosol particles was at its lowest levels for the same addition of kaolin, although the difference between 5 and 10% addition was minimal. The reactor temperature was found to have a minimal effect on both the fly ash and bottom ash properties. PMID- 22081383 TI - Estimation of construction and demolition waste volume generation in new residential buildings in Spain. AB - The management planning of construction and demolition (C&D) waste uses a single indicator which does not provide enough detailed information. Therefore the determination and implementation of other innovative and precise indicators should be determined. The aim of this research work is to improve existing C&D waste quantification tools in the construction of new residential buildings in Spain. For this purpose, several housing projects were studied to determine an estimation of C&D waste generated during their construction process. This paper determines the values of three indicators to estimate the generation of C&D waste in new residential buildings in Spain, itemizing types of waste and construction stages. The inclusion of two more accurate indicators, in addition to the global one commonly in use, provides a significant improvement in C&D waste quantification tools and management planning. PMID- 22081384 TI - The major autolysin Acm2 from Lactobacillus plantarum undergoes cytoplasmic O glycosylation. AB - The major autolysin Acm2 from the probiotic strain Lactobacillus plantarum WCFS1 contains high proportions of alanine, serine, and threonine in its N-terminal so called AST domain. It has been suggested that this extracellular protein might be glycosylated, but this has not been experimentally verified. We used high resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) to study the possible occurrence of glycans on peptides generated from lactobacillary surface proteins by protease treatment. This approach yielded five glycopeptides in various glycoforms, all derived from the AST domain of Acm2. All five glycopeptides contained the hydroxy-amino acids serine and threonine, suggesting that Acm2 is O-glycosylated. By using lectin blotting with succinylated wheat germ agglutinin, and by comparing the wild-type strain with an Acm2-negative derivative (NZ3557), we found that the attached N-acetylhexosamines are most likely N-acetylglucosamines (GlcNAc). NZ3557 was further used as a genetic background to express an Acm2 variant lacking its secretion signal, resulting in intracellular expression of Acm2. We show that this intracellular version of Acm2 is also glycosylated, indicating that the GlcNAc modification is an intracellular process. PMID- 22081385 TI - Genome sequences and phylogenetic analysis of K88- and F18-positive porcine enterotoxigenic Escherichia coli. AB - Porcine enterotoxigenic Escherichia coli (ETEC) continues to result in major morbidity and mortality in the swine industry via postweaning diarrhea. The key virulence factors of ETEC strains, their serotypes, and their fimbrial components have been well studied. However, most studies to date have focused on plasmid encoded traits related to colonization and toxin production, and the chromosomal backgrounds of these strains have been largely understudied. Here, we generated the genomic sequences of K88-positive and F18-positive porcine ETEC strains and examined the phylogenetic distribution of clinical porcine ETEC strains and their plasmid-associated genetic content. The genomes of porcine ETEC strains UMNK88 and UMNF18 were both found to contain remarkable plasmid complements containing known virulence factors, potential novel virulence factors, and antimicrobial resistance-associated elements. The chromosomes of these strains also possessed several unique genomic islands containing hypothetical genes with similarity to classical virulence factors, although phage-associated genomic islands dominated the accessory genomes of these strains. Phylogenetic analysis of 78 clinical isolates associated with neonatal and porcine diarrhea revealed that a limited subset of porcine ETEC lineages exist that generally contain common toxin and fimbrial profiles, with many of the isolates belonging to the ST10, ST23, and ST169 multilocus sequencing types. These lineages were generally distinct from existing human ETEC database isolates. Overall, most porcine ETEC strains appear to have emerged from a limited subset of E. coli lineages that either have an increased propensity to carry plasmid-encoded virulence factors or have the appropriate ETEC core genome required for virulence. PMID- 22081386 TI - Involvement of the global Crp regulator in cyclic AMP-dependent utilization of aromatic amino acids by Pseudomonas putida. AB - The phhAB operon encodes a phenylalanine hydroxylase involved in the conversion of L-phenylalanine into L-tyrosine in Pseudomonas putida. The phhAB promoter is transcribed by RNA polymerase sigma-70 and is unusual in that the specific regulator PhhR acts as an enhancer protein that binds to two distant upstream sites (-75 to -92 and -132 to -149). There is an integration host factor (IHF) binding site that overlaps the proximal PhhR box, and, consequently, IHF acts as an inhibitor of transcription. Use of L-phenylalanine is compromised in a crp deficient background due to reduced expression from the phhAB promoter. Electrophoretic mobility shift assays and DNase I footprinting assays reveal that Crp binds at a site centered at -109 only in the presence of cyclic AMP (cAMP). We show, using circular permutation analysis, that the simultaneous binding of Crp/cAMP and PhhR bends DNA to bring positive regulators and RNA polymerase into close proximity. This nucleoprotein complex promotes transcription from phhA only in response to L-phenylalanine. PMID- 22081387 TI - Deletion of sigma(54) (rpoN) alters the rate of autolysis and biofilm formation in Enterococcus faecalis. AB - Transcription initiation is a critical step in bacterial gene regulation and is often controlled by transcription regulators. The alternate sigma factor (sigma(54)) is one such regulator that facilitates activator-dependent transcription initiation and thus modulates the expression of a variety of genes involved in metabolism and pathogenesis in bacteria. This study describes the role of sigma(54) in the nosocomial pathogen Enterococcus faecalis. Biofilm formation is one of the important pathogenic mechanisms of E. faecalis, as it elevates the organism's potential to cause surgical site and urinary tract infections. Lysis of bacterial cells within the population contributes to biofilm formation by providing extracellular DNA (eDNA) as a key component of the biofilm matrix. Deletion of rpoN rendered E. faecalis resistant to autolysis, which in turn impaired eDNA release. Despite the significant reduction in eDNA levels compared to the parental strain, the rpoN mutant formed more robust biofilms as observed using laser scanning confocal microscopy and Comstat analysis, indicating and emphasizing the presence of other matrix components. Initial adherence to a polystyrene surface was also enhanced in the mutant. Proteinase K treatment at early stages of biofilm development significantly reduced the accumulation of biofilm by the rpoN mutant. In conclusion, our data indicate that other factors in addition to eDNA might contribute to the overall composition of the enterococcal biofilm and that the regulatory role of sigma(54) governs the nature and composition of the biofilm matrix. PMID- 22081388 TI - Newly identified genetic variations in common Escherichia coli MG1655 stock cultures. AB - We have recently identified seven mutations in commonly used stocks of the sequenced Escherichia coli strain MG1655 which do not appear in the reference sequence. The mutations are likely to cause loss of function of the glpR and crl genes, which may have serious implications for physiological experiments using the affected strains. PMID- 22081389 TI - Loss of elongation factor P disrupts bacterial outer membrane integrity. AB - Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits increased uptake of the hydrophobic dye 1-N-phenylnaphthylamine (NPN). Analysis of the membrane proteomes of wild-type and efp mutant Salmonella strains reveals few changes, including the prominent overexpression of a single porin, KdgM, in the efp mutant outer membrane. Removal of KdgM in the efp mutant background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious overexpression of an outer membrane porin. PMID- 22081390 TI - Cj1386 is an ankyrin-containing protein involved in heme trafficking to catalase in Campylobacter jejuni. AB - Campylobacter jejuni, a microaerophilic bacterium, is the most frequent cause of human bacterial gastroenteritis. C. jejuni is exposed to harmful reactive oxygen species (ROS) produced during its own normal metabolic processes and during infection from the host immune system and from host intestinal microbiota. These ROS will damage DNA and proteins and cause peroxidation of lipids. Consequently, identifying ROS defense mechanisms is important for understanding how Campylobacter survives this environmental stress during infection. Construction of a DeltaCj1386 isogenic deletion mutant and phenotypic assays led to its discovery as a novel oxidative stress defense gene. The DeltaCj1386 mutant has an increased sensitivity toward hydrogen peroxide. The Cj1386 gene is located directly downstream from katA (catalase) in the C. jejuni genome. A DeltakatADelta Cj1386 double deletion mutant was constructed and exhibited a sensitivity to hydrogen peroxide similar to that seen in the DeltaCj1386 and DeltakatA single deletion mutants. This observation suggests that Cj1386 may be involved in the same detoxification pathway as catalase. Despite identical KatA abundances, catalase activity assays showed that the DeltaCj1386 mutant had a reduced catalase activity relative to that of wild-type C. jejuni. Heme quantification of KatA protein from the DeltaCj1386 mutant revealed a significant decrease in heme concentration. This indicates an important role for Cj1386 in heme trafficking to KatA within C. jejuni. Interestingly, the DeltaCj1386 mutant had a reduced ability to colonize the ceca of chicks and was outcompeted by the wild-type strain for colonization of the gastrointestinal tract of neonate piglets. These results indicate an important role for Cj1386 in Campylobacter colonization and pathogenesis. PMID- 22081391 TI - Thiosulfate reduction in Salmonella enterica is driven by the proton motive force. AB - Thiosulfate respiration in Salmonella enterica serovar Typhimurium is catalyzed by the membrane-bound enzyme thiosulfate reductase. Experiments with quinone biosynthesis mutants show that menaquinol is the sole electron donor to thiosulfate reductase. However, the reduction of thiosulfate by menaquinol is highly endergonic under standard conditions (DeltaE degrees ' = -328 mV). Thiosulfate reductase activity was found to depend on the proton motive force (PMF) across the cytoplasmic membrane. A structural model for thiosulfate reductase suggests that the PMF drives endergonic electron flow within the enzyme by a reverse loop mechanism. Thiosulfate reductase was able to catalyze the combined oxidation of sulfide and sulfite to thiosulfate in a reverse of the physiological reaction. In contrast to the forward reaction the exergonic thiosulfate-forming reaction was PMF independent. Electron transfer from formate to thiosulfate in whole cells occurs predominantly by intraspecies hydrogen transfer. PMID- 22081392 TI - Evidence that the folate-dependent proteins YgfZ and MnmEG have opposing effects on growth and on activity of the iron-sulfur enzyme MiaB. AB - The folate-dependent protein YgfZ of Escherichia coli participates in the synthesis and repair of iron-sulfur (Fe-S) clusters; it belongs to a family of enzymes that use folate to capture formaldehyde units. Ablation of ygfZ is known to reduce growth, to increase sensitivity to oxidative stress, and to lower the activities of MiaB and other Fe-S enzymes. It has been reported that the growth phenotype can be suppressed by disrupting the tRNA modification gene mnmE. We first confirmed the latter observation using deletions in a simpler, more defined genetic background. We then showed that deleting mnmE substantially restores MiaB activity in ygfZ deletant cells and that overexpressing MnmE with its partner MnmG exacerbates the growth and MiaB activity phenotypes of the ygfZ deletant. MnmE, with MnmG, normally mediates a folate-dependent transfer of a formaldehyde unit to tRNA, and the MnmEG-mediated effects on the phenotypes of the DeltaygfZ mutant apparently require folate, as evidenced by the effect of eliminating all folates by deleting folE. The expression of YgfZ was unaffected by deleting mnmE or overexpressing MnmEG or by folate status. Since formaldehyde transfer is a potential link between MnmEG and YgfZ, we inactivated formaldehyde detoxification by deleting frmA. This deletion had little effect on growth or MiaB activity in the DeltaygfZ strain in the presence of formaldehyde, making it unlikely that formaldehyde alone connects the actions of MnmEG and YgfZ. A more plausible explanation is that MnmEG erroneously transfers a folate-bound formaldehyde unit to MiaB and that YgfZ reverses this. PMID- 22081393 TI - A-type carrier protein ErpA is essential for formation of an active formate nitrate respiratory pathway in Escherichia coli K-12. AB - A-type carrier (ATC) proteins of the Isc (iron-sulfur cluster) and Suf (sulfur mobilization) iron-sulfur ([Fe-S]) cluster biogenesis pathways are proposed to traffic preformed [Fe-S] clusters to apoprotein targets. In this study, we analyzed the roles of the ATC proteins ErpA, IscA, and SufA in the maturation of the nitrate-inducible, multisubunit anaerobic respiratory enzymes formate dehydrogenase N (Fdh-N) and nitrate reductase (Nar). Mutants lacking SufA had enhanced activities of both enzymes. While both Fdh-N and Nar activities were strongly reduced in an iscA mutant, both enzymes were inactive in an erpA mutant and in a mutant unable to synthesize the [Fe-S] cluster scaffold protein IscU. It could be shown for both Fdh-N and Nar that loss of enzyme activity correlated with absence of the [Fe-S] cluster-containing small subunit. Moreover, a slowly migrating form of the catalytic subunit FdnG of Fdh-N was observed, consistent with impeded twin arginine translocation (TAT)-dependent transport. The highly related Fdh-O enzyme was also inactive in the erpA mutant. Although the Nar enzyme has its catalytic subunit NarG localized in the cytoplasm, it also exhibited aberrant migration in an erpA iscA mutant, suggesting that these modular enzymes lack catalytic integrity due to impaired cofactor biosynthesis. Cross-complementation experiments demonstrated that multicopy IscA could partially compensate for lack of ErpA with respect to Fdh-N activity but not Nar activity. These findings suggest that ErpA and IscA have overlapping roles in assembly of these anaerobic respiratory enzymes but demonstrate that ErpA is essential for the production of active enzymes. PMID- 22081394 TI - Structural insights into the catalytic mechanism of Escherichia coli selenophosphate synthetase. AB - Selenophosphate synthetase (SPS) catalyzes the synthesis of selenophosphate, the selenium donor for the biosynthesis of selenocysteine and 2-selenouridine residues in seleno-tRNA. Selenocysteine, known as the 21st amino acid, is then incorporated into proteins during translation to form selenoproteins which serve a variety of cellular processes. SPS activity is dependent on both Mg(2+) and K(+) and uses ATP, selenide, and water to catalyze the formation of AMP, orthophosphate, and selenophosphate. In this reaction, the gamma phosphate of ATP is transferred to the selenide to form selenophosphate, while ADP is hydrolyzed to form orthophosphate and AMP. Most of what is known about the function of SPS has derived from studies investigating Escherichia coli SPS (EcSPS) as a model system. Here we report the crystal structure of the C17S mutant of SPS from E. coli (EcSPS(C17S)) in apo form (without ATP bound). EcSPS(C17S) crystallizes as a homodimer, which was further characterized by analytical ultracentrifugation experiments. The glycine-rich N-terminal region (residues 1 through 47) was found in the open conformation and was mostly ordered in both structures, with a magnesium cofactor bound at the active site of each monomer involving conserved aspartate residues. Mutating these conserved residues (D51, D68, D91, and D227) along with N87, also found at the active site, to alanine completely abolished AMP production in our activity assays, highlighting their essential role for catalysis in EcSPS. Based on the structural and biochemical analysis of EcSPS reported here and using information obtained from similar studies done with SPS orthologs from Aquifex aeolicus and humans, we propose a catalytic mechanism for EcSPS-mediated selenophosphate synthesis. PMID- 22081395 TI - Benzoate mediates repression of C(4)-dicarboxylate utilization in "Aromatoleum aromaticum" EbN1. AB - Diauxic growth was observed in anaerobic C(4)-dicarboxylate-adapted cells of "Aromatoleum aromaticum" EbN1 due to preferred benzoate utilization from a substrate mixture of a C(4)-dicarboxylate (succinate, fumarate, or malate) and benzoate. Differential protein profiles (two-dimensional difference gel electrophoresis [2D DIGE]) revealed dynamic changes in abundance for proteins involved in anaerobic benzoate catabolism and C(4)-dicarboxylate uptake. In the first active growth phase, benzoate utilization was paralleled by maximal abundance of proteins involved in anaerobic benzoate degradation (e.g., benzoyl coenzyme A [CoA] reductase) and minimal abundance of DctP (EbA4158), the periplasmic binding protein of a predicted C(4)-dicarboxylate tripartite ATP independent periplasmic (TRAP) transporter (DctPQM). The opposite was observed during subsequent succinate utilization in the second active growth phase. The increased dctP (respectively, dctPQM) transcript and DctP protein abundance following benzoate depletion suggests that repression of C(4)-dicarboxylate uptake seems to be a main determinant for the observed diauxie. PMID- 22081396 TI - Distinct roles of beta-galactosidase paralogues of the rumen bacterium Mannheimia succiniciproducens. AB - Mannheimia succiniciproducens, a rumen bacterium belonging to the family Pasteurellaceae, has two putative beta-galactosidase genes, bgaA and bgaB, encoding polypeptides whose deduced amino acid sequences share 56% identity with each other and show approximately 30% identity to the Escherichia coli gene for LacZ. The M. succiniciproducens bgaA (MsbgaA) gene-deletion mutant was not able to grow on lactose as the sole carbon source, suggesting its essential role in lactose metabolism, whereas the MsbgaB gene-deletion mutant did not show any growth defect on a lactose medium. Furthermore, the expression of the MsbgaA gene was induced by the addition of lactose in the growth medium, whereas the MsbgaB gene was constitutively expressed independently of a carbon source. Biochemical characterization of the recombinant proteins revealed that MsBgaA is more efficient than MsBgaB in hydrolyzing o-nitrophenyl-beta-d-galactopyranoside and p nitrophenyl-beta-d-galactopyranoside. MsBgaA was highly specific for the hydrolysis of lactose, with a catalytic efficiency of 46.9 s(-1) mM(-1). However, MsBgaB was more efficient for the hydrolysis of lactulose than lactose, and the catalytic efficiency was 10.0 s(-1) mM(-1). Taken together, our results suggest that the beta-galactosidase paralogues of M. succiniciproducens BgaA and BgaB play a critical role in lactose metabolism and in an unknown but likely specific function for rumen bacteria, respectively. PMID- 22081397 TI - Perturbation of FliL interferes with Proteus mirabilis swarmer cell gene expression and differentiation. AB - Proteus mirabilis is a dimorphic, motile bacterium often associated with urinary tract infections. Colonization of urinary tract surfaces is aided by swarmer cell differentiation, which is initiated by inhibition of flagellar rotation when the bacteria first contact a surface. Mutations in fliL, encoding a flagellar structural protein with an enigmatic function, result in the inappropriate production of differentiated swarmer cells, called pseudoswarmer cells, under noninducing conditions, indicating involvement of FliL in the surface sensing pathway. In the present study, we compared the fliL transcriptome with that of wild-type swarmer cells and showed that nearly all genes associated with motility (flagellar class II and III genes) and chemotaxis are repressed. In contrast, spontaneous motile revertants of fliL cells that regained motility yet produced differentiated swarmer cells under noninducing conditions transcribed flagellar class II promoters at consistent levels. Expression of umoA (a known regulator of swarmer cells), flgF, and flgI increased significantly in both swarmer and pseudoswarmer cells, as did genes in a degenerate prophage region situated immediately adjacent to the Rcs phosphorelay system. Unlike swarmer cells, pseudoswarmers displayed increased activity, rather than transcription, of the flagellar master regulatory protein, FlhD(4)C(2), and analyses of the fliL parent strain and its motile revertants showed that they result from mutations altering the C-terminal 14 amino acids of FliL. Collectively, the data suggest a functional role for the C terminus of FliL in surface sensing and implicate UmoA as part of the signal relay leading to the master flagellar regulator FlhD(4)C(2), which ultimately controls swarmer cell differentiation. PMID- 22081398 TI - E622, a miniature, virulence-associated mobile element. AB - Miniature inverted terminal repeat elements (MITEs) are nonautonomous mobile elements that have a significant impact on bacterial evolution. Here we characterize E622, a 611-bp virulence-associated MITE from Pseudomonas syringae, which contains no coding region but has almost perfect 168-bp inverted repeats. Using an antibiotic coupling assay, we show that E622 is transposable and can mobilize an antibiotic resistance gene contained between its borders. Its predicted parent element, designated TnE622, has a typical transposon structure with a three-gene operon, consisting of resolvase, integrase, and exeA-like genes, which is bounded by the same terminal inverted repeats as E622. A broader genome level survey of the E622/TnE622 inverted repeats identified homologs in Pseudomonas, Salmonella, Shewanella, Erwinia, Pantoea, and the cyanobacteria Nostoc and Cyanothece, many of which appear to encompass known virulence genes, including genes encoding toxins, enzymes, and type III secreted effectors. Its association with niche-specific genetic determinants, along with its persistence and evolutionary diversification, indicates that this mobile element family has played a prominent role in the evolution of many agriculturally and clinically relevant pathogenic bacteria. PMID- 22081399 TI - In the NadR regulon, adhesins and diverse meningococcal functions are regulated in response to signals in human saliva. AB - The Neisseria meningitidis regulator NadR was shown to repress expression of the NadA adhesin and play a major role in NadA phase-variable expression. In this study, we identified through microarray analysis over 30 genes coregulated with nadA in the NadR mutant and defined members of the NadR regulon through in vitro DNA-binding assays. Two distinct types of promoter architectures (I and II) were identified for NadR targets, differing in both the number and position of NadR binding sites. All NadR-regulated genes investigated were found to respond to 4 hydroxyphenylacetic acid (4HPA), a small molecule secreted in human saliva, which was previously demonstrated to induce nadA expression by alleviating NadR dependent repression. Interestingly, two types of NadR 4HPA responsive activities were found on different NadR targets corresponding to the two types of genes identified by different promoter architectures: while NadA and the majority of NadR targets (type I) are induced, only the MafA adhesins (type II) are corepressed in response to the same 4HPA signal. This alternate behavior of NadR was confirmed in a panel of strains in response to 4HPA and after incubation in saliva. The in vitro NadR binding activity at type I and type II promoter regions is differentially affected by 4HPA, suggesting that the nature of the NadR binding sites may define the regulation to which they will be subjected. We conclude that NadR coordinates a broad transcriptional response to signals present in human saliva, mimicked in vitro by 4HPA, enabling the meningococcus to adapt to the relevant host niche. PMID- 22081400 TI - Functions of the duplicated hik31 operons in central metabolism and responses to light, dark, and carbon sources in Synechocystis sp. strain PCC 6803. AB - There are two closely related hik31 operons involved in signal transduction on the chromosome and the pSYSX plasmid in the cyanobacterium Synechocystis sp. strain PCC 6803. We studied the growth, cell morphology, and gene expression in operon and hik mutants for both copies, under different growth conditions, to examine whether the duplicated copies have the same or different functions and gene targets and whether they are similarly regulated. Phenotype analysis suggested that both operons regulated common and separate targets in the light and the dark. The chromosomal operon was involved in the negative control of autotrophic events, whereas the plasmid operon was involved in the positive control of heterotrophic events. Both the plasmid and double operon mutant cells were larger and had division defects. The growth data also showed a regulatory role for the chromosomal hik gene under high-CO(2) conditions and the plasmid operon under low-O(2) conditions. Metal stress experiments indicated a role for the chromosomal hik gene and operon in mediating Zn and Cd tolerance, the plasmid operon in Co tolerance, and the chromosomal operon and plasmid hik gene in Ni tolerance. We conclude that both operons are differentially and temporally regulated. We suggest that the chromosomal operon is the primarily expressed copy and the plasmid operon acts as a backup to maintain appropriate gene dosages. Both operons share an integrated regulatory relationship and are induced in high light, in glucose, and in active cell growth. Additionally, the plasmid operon is induced in the dark with or without glucose. PMID- 22081401 TI - The prrAB two-component system is essential for Mycobacterium tuberculosis viability and is induced under nitrogen-limiting conditions. AB - The Mycobacterium tuberculosis prrA-prrB (Rv0903c-Rv0902c) two-component regulatory system is expressed during intracellular growth in human macrophages and is required for early intracellular multiplication in murine macrophages, suggesting its importance in establishing infection. To better understand the function of the prrA-prrB two-component system, we defined the transcriptional characteristics of the prrA and prrB genes during exponential and stationary growth and upon exposure to different environmental stresses and attempted to generate a prrA-prrB deletion mutant. The prrA and prrB genes constitute an operon and are cotranscribed during logarithmic growth, with transcriptional levels decreasing in stationary phase and during hypoxia. Despite the transcriptional differences, PrrA protein levels remained relatively stable throughout growth and in hypoxia. Under conditions of nitrogen limitation, prrAB transcription was induced, while acidic pH stress and carbon starvation did not significantly alter transcript levels. Deletion of the prrAB operon on the chromosome of M. tuberculosis H37Rv occurred only in the presence of an episomal copy of the prrAB genes, indicating that this two-component system is essential for viability. Characterization of the prrAB locus in M. tuberculosis Mt21D3, a previously described prrA transposon mutant, revealed that this strain is not a true prrA knockout mutant. Rather, Tn5367 transposon insertion into the prrA promoter only decreased prrA and prrB transcription and PrrA levels in Mt21D3 compared to those in the parental Mt103 clinical strain. These data provide the first report describing the essentiality of the M. tuberculosis prrAB two component system and reveal insights into its potential role in mycobacterial growth and metabolism. PMID- 22081403 TI - Relative bioavailability of manganese proteinate for broilers fed a conventional corn-soybean meal diet. AB - An experiment was conducted to investigate the bioavailability of organic manganese proteinate (Mn) relative to inorganic Mn sulfate for broilers fed a conventional corn-soybean meal basal diet. A total of 448-day-old Arbor Acres commercial male chicks were fed the Mn-unsupplemented basal diet (control) or basal diet supplemented with 60, 120, or 180 mg Mn/kg from each Mn source. At 21 days of age, heart tissue was excised for testing DM, Mn concentration, manganese superoxide dismutase (MnSOD) activity, and MnSOD mRNA level. The Mn concentration, MnSOD activity, and MnSOD mRNA level in heart tissue increased (P < 0.01) linearly as dietary manganese concentration increased. Based on slope ratios from multiple linear regressions of the above three indices on added Mn level, there was no significant difference (P > 0.21) in bioavailability between Mn proteinate and Mn sulfate for broilers in this experiment. PMID- 22081402 TI - Deficiency in riboflavin biosynthesis affects tetrapyrrole biosynthesis in etiolated Arabidopsis tissue. AB - Tetrapyrrole biosynthesis is controlled by multiple environmental and endogenous cues. Etiolated T-DNA insertion mutants were screened for red fluorescence as result of elevated levels of protochlorophyllide and four red fluorescent in the dark (rfd) mutants were isolated and identified. rfd3 and rfd4 belong to the group of photomorphogenic cop/det/fus mutants. rfd1 and rfd2 had genetic lesions in RIBA1 and FLU encoding the dual-functional protein GTP cyclohydrolase II/3,4 dihydroxy-2-butanone-4-phosphate synthase and a negative regulator of tetrapyrrole biosynthesis, respectively. RIBA1 catalyses the initial reaction of the metabolic pathway of riboflavin biosynthesis and rfd1 contains reduced contents of riboflavin and the flavo-coenzymes FMN and FAD. Transcriptome analysis of rfd1 revealed up-regulated genes encoding nucleus-localized factors involved in cytokinin signalling and numerous down-regulated LEA genes as well as an auxin-inducible GH3 gene. Alteration of cytokinin metabolism of rfd1was confirmed by elevated contents of active forms of cytokinin and stimulated expression of an ARR6::GUS reporter construct. An etiolated quadruple ckx (cytokinin oxidase) mutant with impaired cytokinin degradation as well as different knockout mutants for the negative AUX/IAA regulators shy2-101 (iaa3), axr2-1 (iaa7) and slr-1 (iaa14) showed also excessive protochlorophyllide accumulation. The transcript levels of CHLH and HEMA1 encoding Mg chelatase and glutamyl-tRNA reductase were increased in rfd1 and the AUX/IAA loss-of-function mutants. It is proposed that reduced riboflavin synthesis impairs the activity of the flavin-containing cytokinin oxidase, increases cytokinin contents and de represses synthesis of 5-aminolevulinic acid of tetrapyrrole metabolism in darkness. As result of the mutant analyses, the antagonistic cytokinin and auxin signalling is required for a balanced tetrapyrrole biosynthesis in the dark. PMID- 22081404 TI - Chromium, selenium, and zinc multimineral enriched yeast supplementation ameliorates diabetes symptom in streptozocin-induced mice. AB - Chromium, selenium, and zinc malnutrition has been implicated in the pathogenesis of diabetic mellitus. This study aims to investigate the effects of novel multiminerals-enriched yeast (MMEY) which are minerals supplementation containing elevated levels of chromium, selenium, and zinc simultaneously in a diabetic animal model. Streptozocin-induced diabetic male Balb/c mice (n = 80) were randomly divided into diabetes control group and three treatment groups. They were administrated oral gavages with low, medium, or high doses of MMEY, respectively. Meanwhile, healthy male Balb/c mice (n = 40) of the same body weight were randomly assigned into normal control group and high dose of MMEY control group. After 8 weeks duration of treatment, the animals were sacrificed by cervical dislocation. Serum glucose concentrations, lipid profiles, oxidative/antioxidant, and immunity status were determined. No significant adverse effects were observed in the high-dose MMEY control group. Treatment of the diabetic mice with medium- or high-dose MMEY significantly decreased serum glucose, triglyceride, total cholesterol, and malondialdehyde and increased high density lipoprotein cholesterol, glutathione, and the activities of superoxide dismutase and glutathione peroxidase. In addition, MMEY ameliorated the pathological damage of the pancreatic islets, elevated the thymus or spleen coefficient, and increased the expressions of interleukin-2 and -4 in spleen lymphocytes compared with unsupplemented diabetic mice. In conclusion, these results indicate that supplemental MMEY inhibits hyperglycemia, abates oxidative stress, modulates disorders of lipid metabolism, and reduces the impairment of immune function in diabetic mice; especially notable are the protective effects of medium doses of MMEY on the islet cells of diabetic mice. PMID- 22081405 TI - Zinc upregulates the expression of osteoprotegerin in mouse osteoblasts MC3T3-E1 through PKC/MAPK pathways. AB - Zinc is an essential element for bone formation; however, its role in osteoblast has not been well understood. In the present study, we hypothesized that zinc could increase osteogenetic function by stimulating osteoblast proliferation and osteoprotegerin (OPG) activity. To test this hypothesis, osteoblastic MC3T3-E1 cells were cultured and treated with various concentrations of zinc (0, 10, 30, 50, 70, 110, 130, and 150 MUM) for 24 and 48 h. 3-[4,5-dimethylthiazol-2-y]-2,5 diphenyltetrazolium bromide assay showed that cell proliferation was significantly stimulated with 50 MUM zinc treatment. Furthermore, under the same treatment condition, OPG expression was significantly increased as evidenced by the results of RT-PCR and ELISA. However, the zinc-induced OPG expression was significantly attenuated when MC3T3-E1 cells were co-treated with either protein kinase C (PKC) inhibitor, GF109203X, or the Inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1), PD98059. Moreover, OPG expression was further increased when MC3T3-E1 cells were treated with PMA (the activator of protein of kinase C) in the presence of zinc. These results suggested that zinc would increase osteogenic function by stimulating PKC and MAPK signaling pathways. PMID- 22081406 TI - Regulation of [3H]d-aspartate release by the 5-F(2t)-isoprostane and its 5-epimer in isolated bovine retina. AB - We have evidence that 15-F2-isoprostanes (15-F2-IsoPs) regulate excitatory neurotransmitter release in ocular tissues. Although 5-F2-IsoPs are abundantly produced in mammals, their pharmacological actions on neurotransmitter release remain unknown. In the present study, we compared the effect of the 5-F2-IsoP epimer pair, 5-F(2t)-IsoP (C5-OH in beta-position) and 5-epi-5-F(2t)-IsoP (C5-OH in alpha-position), on K+-evoked [3H]D-aspartate release in isolated bovine retina. We further examined the role of prostanoid receptors on the inhibitory action of 5-epi-5-F(2t)-IsoP on [3H]D-aspartate overflow. Isolated bovine retina were prepared for studies of K+-evoked release of [3H]D-aspartate using the superfusion method. 5-epi-5-F(2t)-IsoP (0.01 nM to 1 MUM), attenuated K+-evoked [3H]D-aspartate release in a concentration-dependent manner, with the inhibitory effect of 26.9% (P < 0.001; IC25 = 0.2 MUM) being achieved at 1 MUM concentration. Its 5-(S)-OH-epimer, 5-F(2t)-IsoP (0.1 nM-1 MUM), exhibited an inhibitory biphasic action, yielding a maximal response of 35.7% (P < 0.001) at 10 nM concentration of the drug (IC25 value of 3 nM). Although the prostanoid receptor antagonists, AH 6809 (10 MUM; EP1-3/DP) and BAY-u3405 (10 MUM; DP/Tx) exhibited no effect on 5-epi-5-F(2t)-IsoP (10 nM-1 MUM)-mediated inhibition, SC 19220 (1 MUM; EP1) completely reversed 5-epi-5-F(2t)-IsoP (0.1 MUM and 1 MUM) induced attenuation of K+-evoked [3H]D-aspartate release. Similarly, both SC 51322 (10 MUM; EP1 and AH 23848 (1 MUM; EP4) reversed the inhibitory action elicited by 5-epi-5-F(2t)-IsoP (0.1 MUM) on the neurotransmitter release. We conclude that the 5-F2-IsoP epimer pair, 5-F(2t)-IsoP and 5-epi-5-F(2t)-IsoP, attenuate K+-induced [3H]D-aspartate release in isolated bovine retina presumably via prostanoid receptor dependent mechanisms. The trans-orientation of the allylic hydroxyl group at position C5 accounts for the apparent biphasic response exhibited by 5-F(2t)-IsoP on excitatory neurotransmitter release. PMID- 22081407 TI - Culturable bacterial communities on leaf sheaths and panicles of rice plants in Japan. AB - Culturable bacterial communities on rice plants were investigated from 2001 to 2003. In total, 1,394 bacterial isolates were obtained from the uppermost leaf sheaths at 1 month before heading time and from leaf sheaths and panicles at heading time. The average culturable bacterial population on the leaf sheaths was larger at heading time than at 1 month previously. Furthermore, the population was significantly larger on panicles than on leaf sheaths, suggesting that the bacterial population is influenced by the organs of rice plants. Larger proportions of bacteria were obtained from the macerates of leaf sheaths after washing with phosphate buffer, and most culturable bacteria were verified to inhabit the inside or inner surface, rather than the outer surface, of the tissues. Verification of the bacterial composition based on 16S rRNA gene sequences revealed that genera of Sphingomonas, Microbacterium, Methylobacterium, and Acidovorax tended to be dominant colonizers on leaf sheaths, whereas Pseudomonas and Pantoea were isolated mainly from the panicles, indicating that leaf sheaths and panicles harbor distinct communities. Furthermore, the richness of bacterial genera was less on both leaf sheaths and panicles at heading time compared with that observed 1 month before heading time. Phylogenetic analyses using bacterial isolates belonging to the four dominant genera inhabiting leaf sheaths at heading time revealed that particular bacterial groups in each genus colonized the leaf sheaths. PMID- 22081408 TI - Dietary shifts and human health: cancer and cardiovascular disease in a sustainable world. AB - INTRODUCTION: Increasing evidence suggests that optimal food choice is critical for sizable prevention of western diseases such as cardiovascular disease and cancer. The Mediterranean diet is an important step in this direction. Moreover, substantially lower rates of Western disease, even compared to Mediterranean countries, have been observed among hunter-gatherers and other non-western populations (Lindeberg 2010). Observational studies and controlled trials support the notion that an evolutionary perspective is helpful when designing food models for optimal human health. DISCUSSION: However, sustainable health for the individual patient is not enough: environmental sustainability must also be considered. Are fish and fruit sustainable for everyone? Are starchy root vegetables a better option than cereal grains? Is locally produced meat an underestimated wholesome food? These and other questions need to be addressed in order to cut greenhouse gases and the consumption of (blue) water and nonrenewable energy. PMID- 22081409 TI - Acute brain damage induced by acetaminophen in mice: effect of diphenyl diselenide on oxidative stress and mitochondrial dysfunction. AB - Organoselenium compounds exhibit antioxidant activity, as well as a variety of biological activities, with potential pharmacological and therapeutic applications. The aim of this study was to investigate the effect of diphenyl diselenide (PhSe)(2) in reversing oxidative brain damage and mitochondrial dysfunction caused by administration of acetaminophen (APAP) in mice. Mice received a toxic dose of APAP, followed by a dose of (PhSe)(2) 1 h later. Four hours after the administration of APAP, plasma was withdrawn from the mice and used for biochemical assays of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as markers of hepatotoxicity. Brain homogenate was examined to determine oxidative stress. Isolated brain mitochondria were examined to quantify mitochondrial transmembrane's electrical potential and mitochondrial swelling and to estimate reactive oxygen species (ROS) production. APAP administration caused an increase in plasma ALT and AST activities. APAP administration also caused a significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and dichlorofluorescein oxidation in brain homogenate. Similarly, mitochondrial swelling and ROS production increased after APAP administration. APAP treatment also caused a decrease in Na(+), K(+)- ATPase activity and in mitochondrial membrane potential. These alterations observed in the brain of APAP-treated mice were restored by (PhSe)(2). Glutathione levels were decreased by APAP, but (PhSe)(2) did not reverse this change. Treatment with (PhSe)(2) after APAP administration can reverse the neurotoxicity caused by a single toxic dose of APAP. The neuroprotective effect of (PhSe)(2) is likely associated with its antioxidant properties. PMID- 22081410 TI - The effect of coenzyme Q10 supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study. AB - OBJECTIVE: It has been shown that coenzyme Q(10) (CoQ(10)) supplementation in men with idiopathic oligoasthenoteratozoospermia (OAT) results in improved semen parameters. In present study, we evaluated the effects of coenzyme CoQ(10) supplementation on semen parameters and pregnancy rates in infertile men with idiopathic OAT. PATIENTS AND METHODS: Two hundred and eighty-seven infertile men with idiopathic OAT were recruited in this study. These patients were treated with CoQ(10) 300 mg orally twice daily for 12 months. Two semen analyses and determination of resting levels of sex hormones were done in all participants. Patients were followed up for another 12 months after CoQ(10) discontinuation. RESULTS: Mean sperm concentration, sperm progressive motility, and sperm with normal morphology improved significantly after 12-month CoQ(10) therapy by 113.7, 104.8, and 78.9%, respectively (all Ps < 0.05). The overall pregnancy rate was 34.1% within a mean of 8.4 +/- 4.7 months. CONCLUSIONS: CoQ(10) supplementation improves semen quality with beneficial effect on pregnancy rate. PMID- 22081411 TI - The quality of life of mothers of children with monosymptomatic enuresis nocturna. AB - BACKGROUND: The purpose of this study was to assess the effect of monosymptomatic nocturnal enuresis (MNE) on the quality of life of the mothers. METHODS: Mothers who have a child with MNE (n = 60) and mothers who have a child without any health problems (n = 90) were included in the study. Groups were similar for background variables (child's age, gender, and number of siblings; mother's age and marital status; and economic status of families and presence of health insurance). The key question was to determine whether or not the difference between the two groups in terms of the quality of life. All mothers underwent Short-Form Health Survey (SF-36) Questionnaire, Spielberg's State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). RESULTS: All SF-36 subscales except social functioning were significantly lower in mothers of enuretic children. The trait-anxiety score, the subcomponent of the STAI, was higher in mothers who have a child with enuresis nocturna (P < 0.001). The mean BDI score was higher in enuretic group (P < 0.001). There was no significant correlation between SF-36, STAI, and BDI scores and child's age, gender, number of siblings, and mother's age. CONCLUSION: This study shows that the quality of life of the mothers was negatively affected by having a child with MNE. PMID- 22081412 TI - Establishing the phylogenetic origin, history, and age of the narrow endemic Viola guadalupensis (Violaceae). AB - PREMISE OF THE STUDY: Climate change and shifts in land use are two major threats to biodiversity and are likely to disproportionately impact narrow endemics. Understanding their origins and the extent of their genetic diversity will enable land managers to better conserve these unique, highly localized gene pools. Viola guadalupensis is a narrow endemic of the Guadalupe Mountains (west Texas, USA). Its affinities within Viola section Chamaemelanium have been the subject of some debate. Furthermore, the polyploid and presumably reticulate relationships within this section remain largely unknown. METHODS: We counted chromosomes for V. guadalupensis. Phylogenies for the chloroplast trnL-F region and the low-copy nuclear gene GPI for 24 Viola taxa were generated and used to produce a polyploid phylogenetic network. Divergence dates were obtained by fossil calibration. KEY RESULTS: Meiotic chromosome counts revealed that V. guadalupensis is tetraploid (n = 12), and the presence of two GPI homoeologs further suggested allotetraploidy. Phylogenetic reconstructions showed that it originated through hybridization between unidentified members of subsection Canadenses (paternal parent) and subsection Nuttallianae (maternal parent). A fossil-calibrated relaxed clock dating analysis of GPI estimated the maximum age of V. guadalupensis to be 8.6 (5.7-11.6) Myr, suggesting the species evolved after the Guadalupe Mountains formed 12-13 Ma. CONCLUSIONS: Viola guadalupensis originated by intersubsectional hybridization followed by polyploidization. Within section Chamaemelanium, this phenomenon has occurred repeatedly in the last 9 Myr (at least for V. bakeri, V. douglasii, V. glabella, and V. sempervirens). Consequences for the systematics of the section are discussed. PMID- 22081413 TI - Subcellular targeting and biosynthesis of cyclotides in plant cells. AB - PREMISE OF THE STUDY: The cyclotide kalata B1 is found in the leaves of Oldenlandia affinis and is a potent insecticidal and nematocidal molecule. This peptide is cleaved from a precursor protein, Oak1, and ligation of the N- and C termini occurs to form a continuous peptide backbone. The subcellular location of the excision and cyclization reactions is unknown, and there is debate as to which enzyme catalyzes the event. To determine where in the plant cell Oak1 is processed, we prepared constructs encoding GFP (green fluorescent protein) linked to the cyclotide precursor Oak1. METHODS: The GFP constructs were transiently expressed in the leaves of Nicotiana benthamiana, and GFP fluorescence was observed in living cells using confocal microscopy. A Fei Mao (FM) styryl dye was infiltrated into whole leaves that were still growing and expressing GFP constructs, enabling the plasma membrane and the tonoplast to be highlighted for visualization of the vacuole in living cells. KEY RESULTS: The full length Oak1 precursor directed GFP to the vacuole, suggesting that excision and cyclization of the cyclotide domain occurs in the vacuole where the cyclotides are then stored. The N-terminal propeptide and N-terminal repeat of Oak1 were both sufficient to target GFP to the vacuole, although the C-terminal propeptide, which is essential for cyclization, was not a targeting signal. CONCLUSIONS: The vacuolar location of cyclotides supports our hypothesis that the vacuolar processing enzyme, asparaginyl endoproteinase, has a pivotal role in excision and cyclization from cyclotide precursors. PMID- 22081414 TI - Convergent evolution of a complex fruit structure in the tribe Brassiceae (Brassicaceae). AB - PREMISE OF STUDY: Many angiosperms have fruit morphologies that result in seeds from the same plant having different dispersal capabilities. A prime example is found in the Brassiceae (Brassicaceae), which has many members with segmented or heteroarthrocarpic fruits. Since only 40% of the genera are heteroarthrocarpic, this tribe provides an opportunity to study the evolution of an ecologically significant novelty and its variants. METHODS: We analyzed nuclear (PHYA) and plastid (matK) sequences from 66 accessions using maximum parsimony, maximum likelihood, and Bayesian inference approaches. The evolution of heteroarthrocarpy and its variants was evaluated using maximum parsimony and maximum likelihood ancestral state reconstructions. KEY RESULTS: Although nuclear and plastid phylogenies are incongruent with each other, the following findings are consistent: (1) Cakile, Crambe, Vella, and Zilla lineages are monophyletic; (2) the Nigra lineage is not monophyletic; and (3) within the Cakile clade, Cakile, Didesmus, and Erucaria are paraphyletic. Despite differences in the matK and PHYA topologies at both deep and shallow nodes, similar patterns of morphological evolution emerge. Heteroarthrocarpy, a complex morphological trait, has evolved multiple times across the tribe. Moreover, there are convergent transitions in dehiscence capabilities and fruit disarticulation across the tribe. CONCLUSIONS: We present the first explicit analysis of fruit evolution within the Brassiceae, which exemplifies evolutionary lability. The repeated loss and gain of segment dehiscence and disarticulation suggests conservation in the genetic pathway controlling abscission with differential expression across taxa. This study provides a strong foundation for future studies of mechanisms underlying variation in dispersal capabilities of Brassiceae. PMID- 22081415 TI - Competition between cytotypes changes across a longitudinal gradient in Centaurea stoebe (Asteraceae). AB - PREMISE OF THE STUDY: Polyploidy resulting from whole genome duplication has contributed to the adaptive evolution of many plant species. However, the conditions necessary for successful polyploid evolution and subsequent establishment and persistence in sympatry with diploid progenitors are often quite limited. One condition thought to be necessary for establishment is a substantial competitive superiority of the polyploid. METHODS: We conducted a pairwise competition experiment using diploid and tetraploid cytotypes of Centaurea stoebe L. to determine whether (1) tetraploids have greater competitive ability than diploids, (2) cytotypes from mixed-cytotype populations have more balanced competitive abilities than single-cytotype populations, and (3) competitive abilities change along a longitudinal gradient. KEY RESULTS: Across sampling localities, tetraploids did not produce greater aboveground biomass than diploids but suffered from greater intracytotypic competition. Tetraploids allocated greater biomass belowground than diploids, regardless of competition treatment, and had greater performance for traits associated with long-term persistence (bolted more frequently and produced more accessory rosettes). Competitive ability of tetraploids did not differ between single- and mixed cytotype populations but varied along a longitudinal gradient. Tetraploids were stronger intercytotypic competitors in Western Europe (Switzerland and Germany) than in Eastern Europe (Hungary and Slovakia), which indicates that cytotype coexistence may be more likely in Eastern Europe, the proposed origin of tetraploids, than in Western Europe. CONCLUSIONS: Our study addresses the importance of examining competitive interactions between cytotypes across their distributional range, as competitive interactions were not consistent across sampling localities. PMID- 22081416 TI - [Transurethral enucleation of bladder paraganglioma]. AB - Paraganglioma of the urinary bladder is a rare neoplasm that derives from ganglion cells located in the bladder wall and may morphologically simulate a urothelial carcinoma. The authors present the case of a vesical paraganglioma incidentally detected by ultrasound, and entirely removed by transurethral approach from detrusorial wall. Conventional approaches include surgery (partial cystectomy) or laparoscopic procedures, with inspection by transurethral endoscopy; in this case we wanted to avoid the combined approach considering the lesion diameter and the possibility of an easy removal. PMID- 22081417 TI - [Laparoscopic adrenalectomy in giant masses]. AB - BACKGROUND: Laparoscopic adrenalectomy is considered the treatment of choice in the surgical management of the most majority of the adrenal diseases. Nevertheless, one of the much discussed topics is the dimensional cut-off for the laparoscopic treatment and it is not clear if laparoscopy should be used in large adrenal masses.Introduction. Laparoscopic adrenalectomy is the goal standard in benign adrenal masses smaller than 6 cm, while its advantages in masses larger than this cut-off and in malignant lesions is still discussed. MATERIALS AND METHODS: We present six cases of laparoscopic adrenalectomy since November 2008 for masses between 7 and 15 cm; 4 men and 2 women. 3 right and 3 left. A complete adrenal endocrinological evaluation demonstrated that the lesions were not secreting tumors. All patients were studied with CT scan.The technique was performed using a flank approach with a 45 degrees tilt. We used 5 trocars in patients who had the masses on the right side, and 4 in those who had the lesions on the left side. After creating an adequate pneumoperitoneum through an open access, the posterior peritoneum cutting, mobilization of the colon, medial dissection of the adrenal gland, and ligation of the main adrenal vein were performed. The adrenal gland was carefully dissected by Ultracision. The mass was extracted by endobag through an additional subcostal port. The mean operative time was 120 minutes. Blood loss was about 50 cc. The drainage was removed on day 2 after surgery and the patient was discharged on day 3. No postoperative complication occurred. The anatomopathologic exam gave evidence of myelolipoma and hemorrhagic cyst. DISCUSSION: The benefits of the laparoscopic approach are widely demonstrated and consist of a shorter hospital stay, reduced morbility, decreased analgesic requirement, and reduced intraoperative blood loss. One of the most discussed topics is the dimensional cut-off and it is not clear if the laparoscopy approach should be used in large adrenal masses (considering the longer operative time and increasing blood loss). Many surgeons performed laparoscopic adrenalectomy for masses of up to 13 cm, thus demonstrating that this procedure is safe and effective. A limitation of laparoscopic approach for adrenal giant masses is the increased risk to treat an adrenal cortical carcinoma. CONCLUSIONS: Our experience, supported by the literature, demonstrates that the laparoscopic adrenalectomy is a feasible and effective surgical technique also in the case of giant masses. Preoperative diagnosis has a predominant role to determine the contraindication of this technique (invasive adrenal carcinoma). PMID- 22081418 TI - [A case of intravesical migration of an intrauterine device detected 14 years later]. AB - We report the case of a patient arrived because of urological symptoms characterized by terminal hematuria, strangury and dysuria due to migration into the bladder of an intrauterine contraceptive device (IUD) placed 14 years before and penetrated into the bladder with formation of lithiasis. These cases have already been described in literature, but the particular feature of this case is that the patient had been pregnant and had a eutocic delivery, she never voluntarily removed the IUD and nor was it found during a gynecologic laparoscopy. The patient underwent the surgical removal of the IUD and of the bladder stone, without detecting adjacent connective routes between uterus and bladder. PMID- 22081419 TI - [Thrombosed aneurysm of a segmental renal artery branch. Diagnostic and therapeutic approach]. AB - INTRODUCTION: We present the case of a 37-year-old man with a thrombosed aneurysm of a segmental branch of the left renal artery, which was diagnosed after a radiological investigation for colic-like pain, and treated conservatively with endovascular approach. MATERIALS AND METHODS: After repeated episodes of colic like pain in his left side with normal ultrasound of the urinary tract, A.R. (37 years old) undergoes a CT urogram of the abdomen, which shows a complete thrombosis of the middle third of the left renal artery, which is associated with hypoperfusion of the lower middle third of the kidney with suspected ischemia of the lower pole. In confirmation of the previous clinical scenario, we proceed with a urgent angiography, which identifies a pseudo-aneurysm, partially thrombosed, of the segmental branch of the left renal artery at the lower middle pole. During the hospitalization, the clinical picture is complicated by an unstable arterial hypertension associated with headache and nausea. A renal scintigraphy confirms a severe impairment of the renal function mainly at the level of the middle third of the lower left kidney. The total glomerular filtration rate sec. Gates was equal to 64.3 mL/min with a percentage breakdown of the global renal function of 28% to the right and 72% to the left. The location of the vascular defect argues for endovascular intervention in the attempt to preserve the remaining renal parenchyma. We proceed with a standard angiography with selective access to the left renal artery with a catheter via femoral artery Cobra 5Fx80 TERUSMO cm. The tortuosity of the thrombus and the angle of the aneurysm site prevent, despite several attempts, the passage of the guide wire for a possible stenting and fibrinolysis. We opt for the placement of 5 spirals at the aneurysm (Boston Soft GDC-10 SR 360 7mm x 15cm), in order to preserve the residual parenchyma, excluding the aneurysmal artery at risk of rupture and extent of the thrombus. RESULTS: Immediately after the procedure, the clinical picture remained stable with complete remission of painful symptoms and with a good blood pressure control. At about 6 months, the renal scintigraphy shows a filtered global impairment of 70%, 30% for the left kidney, a slight improvement over the previous controls. The blood pressure remains within the limits with amlodipine 5 mg. CONCLUSIONS: Renal artery aneurysms are uncommon and occur in approximately 0.09% of the general population. The etiopathogenesis at a young age is often dysplastic in nature and the diagnosis is made incidentally or during evaluation of related symptoms, being asymptomatic until they become complicated. Their treatment is proposed to prevent complications such as rupture or thrombosis. Given the extreme variability of presentation, the surgical technique, traditional or endoscopic, is at the surgeon's discretion. In our case, we opted for a conservative approach since the degree of renal parenchyma impairment and the patient's hemodynamic condition allowed to. PMID- 22081420 TI - Ex vivo models for training in endourology: construction of the model and simulation of training procedures. AB - BACKGROUND: Training in endourology by ex vivo models is an effective tool for unskilled urologists to get qualification. Urologists have different kinds of training models at urological conferences, but, in order to get skilled, they need models available at their own department. METHODS: The article describes how to build an ex vivo porcine model to train on the main endourological procedures. RESULTS: Questionnaires filled by the trainers attending the courses at our department, over the last three years, have proved the high degree of satisfaction about this kind of training system. CONCLUSIONS: Validation studies about these models still lack. The growing interest about them requires randomized controlled validation studies in the future, including large numbers of participants. PMID- 22081421 TI - [Multiple stones in atypical heterotopic reservoir in a patient with renal transplant: endourologic resolution]. AB - BACKGROUND: Urolithiasis is a frequent complication in a heterotopic reservoir and the surgical management could be a difficult problem. Open surgery is not recommended in patients with multiple previous surgeries. A less invasive technique, such as the endourologic procedures, would allow high stone-free rate and low surgical morbidity. INTRODUCTION: Stone formation in the reservoir is a well-known complication of urinary diversion. The incidence of lithiasis in patients with continent urinary diversion is reported as 12-52.5%. Most patients will have multiple physical factors, such as immobility, need for self catheterization and poor urine drainage, so that it is not certain that an intestinal reservoir is the cause of stones on its own. The management of urolithiasis in continent urinary diversion can be challenging and could be a difficult problem to solve. A less invasive technique, such as the endourologic procedures, is desiderable, especially in patients with kidney transplant and low immune defence. MATERIALS AND METHODS: We present the case of a 59-year-old woman with previous history of spina bifida and with neurogenic bladder. At a pediatric age, she underwent incontinent urinary diversion using a sigmo-colic conduit. For several years she had been suffering from kidney stones and recurrent urinary infections, which led to a left nephrectomy for pyonephrosis, subsequent deterioration of renal function and dialysis. In 2004, we performed an atypical continent and self-catheterizable reservoir using the previous colic conduit detubularized and ileum-cecal tract with Mitrofanoff system conduit of 14 Fr size. Finally, kidney transplant was carried out as last surgical procedure. Recently she has come to our attention for multiple and large reservoir stones. SURGICAL TECHNIQUE: preliminary exploration of the continent pouch with flexible cystoscope. Percutaneous access with Endovision degrees direct control through the afferent conduit with 8 Fr flexible ureteroscope. Dilation of percutaneous tract with pneumatic balloon and positioning 30 Fr Amplats sheet. Lithotripsy, with ultrasound and ballistic sources, was performed and the residual fragments were removed with grasping. At the end of the procedure, after controlling the complete clearance with flexible nephroscope and X-ray, a percutanous 12 Fr catheter and a 12 Fr Foley in the Mitrofanoff conduit were inserted. RESULTS: No fever or increase serum creatinine were observed in the post-operative time. On day 3, we removed the percutaneous foley and after 7 days we performed a cystography with a normal pouch configuration; no leakage or residual fragments were observed. The woman was discarge and returned to usual self-catheterization. The first 3-month post-operative control was regular; no infections or pain were reported. CONCLUSIONS: In special cases, like this one, the percutaneous procedure is preferred to open surgery for a best control of the pouch and a simple complete clearence of the fragments. PMID- 22081422 TI - [Endoscopic treatment with Wallgraft stenting of complete iatrogenic iliac ureteral injury in a high-risk surgical patient]. AB - BACKGROUND: Injury of the ureter is a potential complication of any difficult abdominopelvic surgical procedure, with an incidence ranging between 0.5% and 10% in most series. The treatment depends on the severity and the place of the lesion. The severe mid and upper ureteral injuries usually require complex treatment procedures, which can be contraindicated in case of severe comorbidities with high anesthesiologic risk. We report our experience in the endoscopic treatment with Wallgraft stenting of complete iatrogenic iliac ureteral injury in a high-risk surgical patient. METHODS: A 74-year-old female patient was admitted at our department due to a complete lesion of the right iliac ureter following right iliac artery aneurysm repair with iatrogenic ileal injury. The patient was in coma, affected by severe respiratory insufficiency, sepsis and uroperitoneum. These conditions contraindicated a general anesthesia encumbering the positioning of a nephrostomy, and influenced our indication of Wallgraft stent placement. The Wallgraft endoprosthesis (10 x 50 mm) is a self expanding super-alloy metallic high flexible stent covered by PET, which can be placed at the level of the lesion using fluoroscopy after introducing an angiographic catheter and guidewire. This procedure is usually indicated in the treatment of vascular lesions. RESULTS: After positioning the Wallgraft stent, pyelography showed a complete closure of the lesion. The patient's clinical condition improved quickly and remained stable at a follow-up of 45 months. CONCLUSIONS: Although the Wallgraft stent positioning cannot be considered as a standard treatment for all the complete ureteral lesions, it can be proposed in the management of some patients with severe comorbidities, which do not allow any other approach. PMID- 22081423 TI - Surgery and target agents for renal cell carcinoma treatment: the path between proper interaction. AB - BACKGROUND: Renal cell carcinoma accounts for 3% of all solid tumors and currently causes about 3,500 deaths/year in the UK. Once an orphan disease, it has undergone an impressive change in its natural history with an improvement in overall survival, thanks to the development of new target agents. INTRODUCTION: In its management, renal cell carcinoma has been treated with both surgical and medical approaches. Nowadays, many more drugs are available, especially in the metastatic setting, so that we should reconsider the peculiar role of surgery and its interaction with target agents. CONCLUSIONS: Cytoreductive nephrectomy still plays a major role in the management of the disease, though no really solid data have been still obtained. Adjuvant and neoadjuvant settings, instead, are still under evaluation, especially new adjuvant therapies involving the numerous target agents we have. Finally, metastasectomy has a controversial role, with some evidence of more efficacy than the medical treatment, though it shows too many biases to be considered certain. The picture that comes out suggests a complex frame, in which we have great power to act, but in which we need to better comprehend the interactions that could be created between surgery and medical therapies, to achieve an optimal multimodal treatment for renal cell carcinoma. PMID- 22081424 TI - Proteomic characterization of the late and persistent effects of cadmium at low doses on the rat liver. AB - To investigate the late and persistent effects of cadmium (Cd) at low doses on the liver and its potential mechanisms, male Wistar rats were given i.p. injection of Cd as CdCl2 at 20 nmol kg(-1) body weight every other day for 4 weeks. At weeks 20, 44 and 52, the livers from Cd-treated and age-matched control rats were examined pathologically and biochemically. Chronic exposure of rats to Cd at low doses induced mild pathological changes and persistent oxidative damage as well as cell proliferation. Hepatic proteins were analyzed with two dimensional electrophoresis (2-DE) and mass spectrometry. More than 1000 protein spots were detected by 2-DE. Ten proteins were distinguishable between Cd-treated and age-matched control groups at week 52 week after Cd treatment. Two of them were significantly down-regulated: prohibitin (PHB) and d-dopachrome tautomerase (DDT). By western blotting the down-regulated expression of PHB and DDT in the livers of Cd-treated rats was confirmed in both early (week 20) and late (week 52) time points. To further examine the down-regulation of antioxidant status in the Cd-treated livers, other common antioxidants, including superoxide dismutase and glutathione and one metal detoxification specific protein metallothionein, were also detected and found to be decreased, particularly at the late stage. These results suggest that mild histopathological changes, persistent oxidative damage and cell proliferation remained at the late stages (weeks 44-52) after rats were exposed to low-dose Cd. These persistent changes may be associated with the persistent down-regulation of cellular antioxidant systems. PMID- 22081425 TI - MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9. AB - Evidence for a regulatory role of the miR-34 family in senescence is growing. However, the exact role of miR-34 in aging in vivo remains unclear. Here, we report that a mir-34 loss-of-function mutation in Caenorhabditis elegans markedly delays the age-related physiological decline, extends lifespan, and increases resistance to heat and oxidative stress. We also found that RNAi against autophagy-related genes, atg4, bec-1, or atg9, significantly reversed the lifespan-extending effect of the mir-34 mutants. Furthermore, miR-34a inhibits Atg9A expression at the post-transcriptional level in vitro, and the miR-34a binding sequences in the 3'-UTR of Atg9A contributes to the modulation of Atg9A expression by miR-34a. Our results demonstrate that the C. elegans mir-34 mutation extends lifespan by enhancing autophagic flux in C. elegans, and that miR-34 represses autophagy by directly inhibiting the expression of the autophagy related proteins Atg9 in mammalian cells. PMID- 22081426 TI - A multimeasure approach to investigating affective appraisal of social information in Williams syndrome. AB - People with Williams syndrome (WS) have been consistently described as showing heightened sociability, gregariousness, and interest in people, in conjunction with an uneven cognitive profile and mild to moderate intellectual or learning disability. To explore the mechanisms underlying this unusual social-behavioral phenotype, we investigated whether individuals with WS show an atypical appraisal style and autonomic responsiveness to emotionally laden images with social or nonsocial content. Adolescents and adults with WS were compared to chronological age-matched and nonverbal mental age-matched groups in their responses to positive and negative images with or without social content, using measures of self-selected viewing time (SSVT), autonomic arousal reflected in pupil dilation measures, and likeability ratings. The participants with WS looked significantly longer at the social images compared to images without social content and had reduced arousal to the negative social images compared to the control groups. In contrast to the comparison groups, the explicit ratings of likeability in the WS group did not correlate with their SSVT; instead, they reflected an appraisal style of more extreme ratings. This distinctive pattern of viewing interest, likeability ratings, and autonomic arousal to images with social content in the WS group suggests that their heightened social drive may be related to atypical functioning of reward-related brain systems reflected in SSVT and autonomic reactivity measures, but not in explicit ratings. PMID- 22081427 TI - Glomerular expression of apelin and its association with proteinuria. AB - OBJECTIVE: To investigate the distribution and expression of apelin in kidney of adriamycin (ADR)-induced nephrotic rats, and to explore the possible association of apelin expression with the development of proteinuria. METHODS: Immunohistochemical staining for apelin was used to examine the expression and distribution of apelin in kidney of adriamycin (ADR)-induced nephrotic rats at 7, 14, 21 and 28 d after adriamycin injection. The level of serum apelin at 7, 14, 21 and 28 d after ADR injection was also determined with ELISA methods. Moreover the correlation of urine protein and glomerular expression of apelin was analyzed. RESULTS: The apelin protein was immunohistochemically detected along glomerular basement membrane (GBM) in the kidney of rats and significantly increased compared with normal control rats after ADR injection. The levels of 24 h proteinuria and serum apelin were also elevated after ADR injection. Moreover the production of proteinuria was correlated positively with the expression of apelin in kidney tissue (rs = 0.9427, P < 0.01). CONCLUSIONS: The glomerular expression of apelin increased significantly in ADR rats, which is correlated with urine protein. PMID- 22081428 TI - History of growth hormone therapy. AB - The first human to receive GH therapy was in 1956; it was of bovine origin and was given for 3 wk for metabolic balance studies revealing no effects. By 1958, three separate laboratories utilizing different extraction methods retrieved hGH from human pituitaries, purified it and used for clinical investigation. By 1959 presumed GHD patients were being given native hGH collected and extracted by various methods. Since 1 mg of hGH was needed to treat one patient per day, >360 human pituitaries were needed per patient per year. Thus, the availability of hGH was limited and was awarded on the basis of clinical research protocols approved by the National Pituitary Agency (NPA) established in 1961. hGH was dispensed and injected on a milligram weight basis with varied concentrations between batches from 0.5 units/mg to 2.0 units/mg of hGH. By 1977 a centralized laboratory was established to extract all human pituitaries in the US, this markedly improved the yield of hGH obtained and most remarkably, hGH of this laboratory was never associated with Creutzfeld-Jacob disease (CJD) resulting from the injection of apparently prior- contaminated hGH produced years earlier. However, widespread rhGH use was not possible even if a pituitary from each autopsy performed in the US was collected, this would only permit therapy for about 4,000 patients. Thus, the mass production of rhGH required the identification of the gene structure of the hormone, methodology that began in 1976 to make insulin by recombinant technology. Serendipity was manifest in 1985 when patients who had received hGH years previously were reported to have died of CJD. This led to the discontinuation of the distribution and use of hGH, at a time when a synthetic rhGH became available for clinical use. The creation of a synthetic rhGH was accompanied by unlimited supplies of hGH for investigation and therapy. However, the appropriate use and the potential abuse of this hormone are to be dealt with. The illegitimate use of rhGH, unequivocally the abuse by athletes is, and should be, of primary concern to society and should be halted. The abuse of prescribing rhGH in an attempt to retard the aging process also should receive attention. PMID- 22081430 TI - New evidence for a role of MICA in the pathogenesis of systemic lupus erythematosus: comment on the article by Yoshida et al. PMID- 22081429 TI - An emerging role of degrading proteinases in hypertension and the metabolic syndrome: autodigestion and receptor cleavage. AB - One of the major challenges for hypertension research is to identify the mechanisms that cause the comorbidities encountered in many hypertensive patients, as seen in the metabolic syndrome. An emerging body of evidence suggests that human and experimental hypertensives may exhibit uncontrolled activity of proteinases, including the family of matrix metalloproteinases, recognized for their ability to restructure the extracellular matrix proteins and to play a role in hypertrophy. We propose a new hypothesis that provides a molecular framework for the comorbidities of hypertension, diabetes, capillary rarefaction, immune suppression, and other cell and organ dysfunctions due to early and uncontrolled extracellular receptor cleavage by active proteinases. The proteinase and signaling activity in hypertensives requires further detailed analysis of the proteinase expression, the mechanisms causing proenzyme activation, and identification of the proteinase substrate. This work may open the opportunity for reassessment of old interventions and development of new interventions to manage hypertension and its comorbidities. PMID- 22081431 TI - Conditional deletion of Stat3 in mammary epithelium impairs the acute phase response and modulates immune cell numbers during post-lactational regression. AB - Mammary gland regression following weaning (involution) is associated with extensive cell death and the acquisition of an inflammatory signature. Characterizing the interplay between mammary epithelial cells, the re-emerging stroma and immune cells has implications for the understanding of the pathogenesis of pregnancy-associated breast cancer. Stat3 has a role in orchestrating cell death and involution, and we sought to determine whether expression of Stat3 by the mammary epithelium also influences the innate immune environment and inflammatory cell influx in the gland. We examined mice in which Stat3 is conditionally deleted only in the mammary epithelium. Distinct sets of genes associated with the acute phase response and innate immunity are markedly up-regulated during first phase involution in a Stat3-dependent manner. During second phase involution, chitinase 3-like 1, which has been associated with wound healing and chronic inflammatory conditions, is dramatically up-regulated by Stat3. Also at this time, the number of mammary macrophages and mast cells increases per unit area, and this increase is impaired in the absence of epithelial Stat3. Furthermore, expression of arginase-1 and Ym1, markers of alternatively activated macrophages, is significantly decreased in the absence of Stat3, whilst iNOS, a marker associated with classically activated macrophages, shows significantly increased expression in the Stat3-deleted glands. Thus, Stat3 is a key transcriptional regulator of genes associated with innate immunity and wound healing and influences mammary macrophage and mast cell numbers. The presence of epithelial Stat3 appears to polarize the macrophages and epithelial cells towards an alternatively activated phenotype, since in the absence of Stat3, the gland retains a phenotype associated with classically activated macrophages. These findings have relevance to the study of pregnancy-associated breast cancer and the role of Stat3 signalling in recruitment of alternatively activated tumour-associated macrophages in breast cancer. PMID- 22081432 TI - Two length variants of the microsatellite FH2295 as markers for body size of female Portuguese water dogs. AB - Genetic studies in purebred Portuguese water dogs (PWD) have previously identified genetic loci controlling skeleton size. The FH2295 genetic marker was reported to control 43.6% of the size variation in this breed. In the present study, we amplified and sequenced the genomic DNA from female PWD of different sizes in the region of the FH2295 genetic marker. Polymerase chain reaction (PCR) products of 700 and 800 bp were generated and sequencing revealed the presence of a microsatellite marker including either 5 or 24 repeats of the tetranucleotide sequence "CTTT". Dogs were divided into groups based on their genotypes: homozygote for the short allele (II) or homozygote for the long allele (BB) or heterozygote (IB). The smallest dogs were homozygous with 24 repeats and the largest dogs were homozygous with five repeats. Genetic transmission of the microsatellite marker appears to follow Mendelian laws since all puppies born to a homozygous small dog genotyped "BB" included one or two "B" allele. We applied a PCR method to characterize the sequence of the previously identified dog genetic marker FH2295 and propose that the length of the microsatellite identified could be used as a predictor for the body size of female PWD. PMID- 22081433 TI - Characterization of the hepatic cellular uptake of alpha(1) -acid glycoprotein (AGP), part 1: a peptide moiety of human AGP is recognized by the hemoglobin beta chain on mouse liver parenchymal cells. AB - Human alpha(1) -acid glycoprotein (AGP), a serum glycoprotein, is known to have anti-inflammatory activity. We recently reported that AGP was mainly incorporated into the liver in mice via a receptor-mediated pathway, although the mechanism for this was largely unknown. The objective of this study was to identify the specific cellular surface protein that recognizes the peptide moiety of AGP. Pharmacokinetic studies of (111) In-AGP and (111) In -recombinant glycan deficient AGP (rAGP) in mice demonstrated that both AGPs are mainly distributed to the liver and kidney, but hepatic and renal uptake clearance of rAGP was higher than that for AGP. Hepatic uptake of rAGP was inhibited in the presence of 100-fold excess of unlabeled AGP, indicating that the hepatic uptake of rAGP shared a common route with that of AGP and that it recognized the peptide moiety of AGPs. In ligand blotting analyses using crude cellular membrane fraction of mice liver, a band corresponding to a 16 kDa protein was observed to bind to both AGPs. Interestingly, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry MALDI-TOF-MS and western blotting analyses indicated that this 16 kDa protein is the hemoglobin beta-chain (HBB). It, therefore, appears that HBB is associated with the hepatic uptake of AGP via a direct interaction with its peptide moiety. PMID- 22081434 TI - Pruritus in primary myelofibrosis: clinical and laboratory correlates. AB - Recent clinical trials with JAK or mammalian target of rapamycin (mTOR) inhibitors in primary myelofibrosis (PMF) have identified pruritus as one of the most treatment-responsive disease traits. However, little is known about the prevalence of pruritus in PMF or its clinical and laboratory correlates. Among 566 consecutive patients with PMF seen at our institution, the presence or absence of pruritus was documented in 90 (16%) and 146 (26%) patients, respectively. Patients with pruritus were less likely to express MPLW515 (0% vs. 10%; P = 0.02) or leukopenia (8% vs. 24%; P = 0.002). The latter association was more pronounced in the absence of JAK2 or MPL mutations. Pruritus also clustered with marked leukocytosis (23% vs. 11%; P = 0.01) and JAK2V617F (71% vs. 59%; P = 0.08). Pruritus did not correlate with karyotype (P = 0.33), risk category per the Dynamic International Prognostic Scoring System (DIPSS)-plus (P = 0.37), DIPSS-plus-adjusted survival (P = 0.41), or leukemic transformation (P = 0.13). Plasma levels of 20 cytokines, which are known to be abnormally expressed in PMF, including IL-1b, IL-2R, IL-6, IL-8, and VEGF, were measured in 63 informative cases and showed no correlations with history of pruritus. We conclude that pruritus is relatively frequent in PMF and is prognostically irrelevant. The pathogenesis of PMF-associated pruritus is not necessarily linked to proinflammatory cytokines but may instead involve molecules that are either granulocyte-derived or influence granulopoiesis. The apparently differential effect of MPL vs. JAK2 mutations on pruritus requires further investigation. PMID- 22081435 TI - Biowaiver monographs for immediate-release solid oral dosage forms: quinine sulfate. AB - The biowaiver approach permits evaluation of bioequivalence (BE) using a set of laboratory tests, obviating the need for expensive and time-consuming pharmacokinetic BE studies provided that both the active pharmaceutical ingredient and the formulations can meet the specified criteria. In the present monograph, the biowaiver-relevant data including solubility and permeability data, therapeutic use and therapeutic index, pharmacokinetic properties, reported excipient interactions, and BE/bioavailability studies of quinine sulfate are itemized and discussed. Quinine sulfate has borderline solubility characteristics and, on the whole, is highly permeable. Thus, depending on the jurisdiction, it is assigned to Biopharmaceutics Classification System class I or II. Although these characteristics would suggest a low risk of bioinequivalence among oral quinine products, a recent pharmacokinetic study showed bioinequivalence of two products. Even though quinine does not, strictly speaking, fit the definition of a narrow therapeutic index drug, it shows dose-related and, in some cases, irreversible side effects and toxicities at concentrations not far above the therapeutic concentration range. Taking all relevant aspects into consideration, a biowaiver cannot be recommended for new quinine immediate-release multisource products or major post-approval changes of already marketed quinine products, and in such cases, BE should be evaluated using an in vivo BE study. PMID- 22081436 TI - Expression of Th17 cells in breast cancer tissue and its association with clinical parameters. AB - Th17 cells are newly identified effector CD4(+) T cells, which play an active role in inflammation and autoimmune diseases and may be relevant for anti-tumor defenses. In the present study, we examined expression of Th17 cells in specimens of breast cancer tissue and its association with clinical, pathology, and immunological parameters. Expression rates of Th17 and T regulatory (Treg) cells in breast cancer and normal (i.e. non-cancerous) tissue were evaluated using flow cytometry in 30 patients with breast carcinoma. Further, expression of interleukin-17 (IL-17), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in breast cancer tissue was evaluated by immunohistochemical staining. Associations between Th17 expression and other parameters were analyzed by multiple linear regression analysis. We observed that expression of Th17 cells was significantly higher in breast cancer compared to normal breast tissue. Further, expressions of IL-17, IL-1beta, and IL-6 in cancer tissue positively correlated with expression of Th17 cells. In addition, there was a negative association between the numbers of Th17 cells and TNM stage, blood vessel invasion, and increased numbers of metastatic lymph nodes. Finally, expression of Th17 was not associated with expression of Treg. In conclusion, Th17 cells appear to be involved in anti-tumor immune responses and are associated with a more favorable prognosis. PMID- 22081437 TI - TNF-alpha increases bone marrow mesenchymal stem cell migration to ischemic tissues. AB - The objective of this study was to analyze the influence of TNF-alpha on rat mesenchymal stem cells (MSCs) and to assess feasibility of MSC transplantation to repair ischemic injury. In this study, adhesion molecules and cell specific surface markers on MSCs were measured after exposure to different concentrations of TNF-alpha. MSCs stimulated with varying concentrations of TNF-alpha were cultured with aortic endothelial cells, and the adhesion rate was measured. MSCs were then stimulated with an optimum concentration of TNF-alpha as determined in vitro, and injected intravenously into rats with ischemic hind limb injury. The number of MSCs in muscle samples from the ischemic area was counted. The results showed that (1) TNF-alpha induced a concentration-dependent increase in VCAM-1 expression in MSCs, whereas the expression of L-selectin, ICAM-1 and VLA-4 did not change significantly. Expression of MSC-specific antigens was unchanged. (2) MSCs pretreated with 10 ng/ml TNF-alpha showed significantly increased adhesion to endothelial cells in vitro, and accumulated to a greater extent in the areas of ischemic damage in rat hind limbs. We were able to conclude that TNF-alpha has no effect on expression of MSC-specific markers, but can increase the expression of VCAM-1 on rat MSCs. Suitable concentrations of TNF-alpha can promote MSC adhesion to endothelial cells and migration to damaged tissue. PMID- 22081438 TI - Complications of implantable venous access devices in patients with sickle cell disease. AB - Implantable venous access devices (VADs) are used in sickle cell disease (SCD) for patients with poor venous access to facilitate chronic blood transfusions and manage acute complications. We attempted to define the frequency of bloodstream infections (BSI) and thrombosis in adults and children with SCD and VADs. We performed a single-institution, retrospective review of VAD-associated infection and thrombosis in patients with SCD. Thirty-two patients (median age 20 years, range, 1-59) had 86 VADs placed (median, 2.7 VADs per patient, range, 1-7) with a total of 41,292 catheter days (median, 1,376 days; range, 323-3,999). Mean catheter lifespan in adults (691 days +/- 123) was not significantly higher than children (614 days +/- 154). A total of 66 VAD-associated BSI (1.59 infections per 1,000 catheter days) occurred in 17 of 32 (53%) patients. Children with VADs had fewer BSI (3 of 10; 30%) than adults (14 of 22; 64%, P = 0.08). 24 catheter associated thromboses (0.49 thromboses per 1,000 catheter days) occurred in 10 of 32 (41%) of patients. Children also had fewer VAD-associated-thrombosis (1 of 10; 10%) than adults (9 of 22; 40%, P = 0.08). In conclusion, the use of VADs in SCD was linked to a significant rate of infection and thrombosis. PMID- 22081439 TI - A linear mixed model for predicting a binary event from longitudinal data under random effects misspecification. AB - The use of longitudinal data for predicting a subsequent binary event is often the focus of diagnostic studies. This is particularly important in obstetrics, where ultrasound measurements taken during fetal development may be useful for predicting various poor pregnancy outcomes. We propose a modeling framework for predicting a binary event from longitudinal measurements where a shared random effect links the two processes together. Under a Gaussian random effects assumption, the approach is simple to implement with standard statistical software. Using asymptotic and simulation results, we show that estimates of predictive accuracy under a Gaussian random effects distribution are robust to severe misspecification of this distribution. However, under some circumstances, estimates of individual risk may be sensitive to severe random effects misspecification. We illustrate the methodology with data from a longitudinal fetal growth study. PMID- 22081440 TI - Sleep problems and risk of fibromyalgia: longitudinal data on an adult female population in Norway. AB - OBJECTIVE: Sleep problems are common among patients with fibromyalgia (FM). However, it is not known whether poor sleep is a contributing factor in FM or a consequence of the illness. The aim of the current study was to prospectively investigate the association between self-reported sleep problems and risk of FM among adult women. METHODS: We longitudinally studied 12,350 women who did not have FM, musculoskeletal pain, or physical impairments at baseline (1984-1986). A generalized linear model was used to calculate the adjusted relative risk (RR) of FM at followup in 1995-1997. RESULTS: Incident FM was reported by 327 women at followup. A dose-dependent association was found between sleep problems and risk of FM (P for trend<0.001), with an adjusted RR of 3.43 (95% confidence interval [95% CI] 2.26-5.19) among women who reported having sleep problems often or always, compared to women who never experienced sleep problems. Age-stratified analysis showed that women age>=45 years who reported having sleep problems often or always had an adjusted RR of 5.41 (95% CI 2.65-11.05), whereas the corresponding RR for women ages 20-44 years who reported having sleep problems often or always was 2.98 (95% CI 1.76-5.05). CONCLUSION: These prospective data indicate a strong dose-dependent association between sleep problems and risk of FM. The association is somewhat, although not significantly, stronger in middle aged and older women than in younger women. PMID- 22081441 TI - Effect of short- and long-term strength exercise on cardiac oxidative stress and performance in rat. AB - Increase in heart metabolism during severe exercise facilitates production of ROS and result in oxidative stress. Due to shortage of information, the effect of chronic strength exercise on oxidative stress and contractile function of the heart was assessed to explore the threshold for oxidative stress in this kind of exercise training. Male Wistar rats (80) were divided into two test groups exercised 1 and 3 months and two control groups without exercise. Strength exercise was carried by wearing a Canvas Jacket with weights and forced rats to lift the weights. Rats were exercised at 70% of maximum lifted weight 6 days/week, four times/day, and 12 repetitions each time. Finally, the hearts of ten rats/group were homogenized and MDA, SOD, GPX, and catalase (CAT) were determined by ELISA method. In other ten rats/group, left ventricle systolic and end diastolic pressures (LVSP and LVEDP) and contractility indices (LVDP and +dp/dt max) and relaxation velocity (-dp/dt max) were recorded. The coronary outflow was collected. Short- and long-term strength exercise increased heart weight and heart/BW ratio (P < 0.05). In the 3-month exercise group, basal heart rate decreased (P < 0.05). LVEDP did not change but LVDP, +dp/dt max, -dp/dt max, and coronary flow significantly increased in both exercise groups (P < 0.05). None of MDA or SOD, GPX, and CAT significantly changed. The results showed that sub-maximal chronic strength exercise improves heart efficiency without increase in oxidative stress index or decrease in antioxidant defense capacity. These imply that long-time strength exercise up to this intensity is safe for cardiac health. PMID- 22081442 TI - Different regulation role of myostatin in differentiating pig ADSCs and MSCs into adipocytes. AB - Myostation (MSTN), which is primarily expressed in muscle, plays an important role in myogenic and adipogenic cells. However, there is little information about whether MSTN displays different roles between adipose-derived stem cells (ADSCs) and muscle satellite cells (MSCs). The two kinds of cells can both exist in the muscle and differentiate into adiposities. In this research, we isolated ADSCs and MSCs from porcine fat tissues and semitendinosus muscle, respectively, to investigate the effect of MSTN on the adipogenesis of those cells. ADSCs and MSCs were treated with recombinant human MSTN during the induction of adipogenesis or before the induction of differentiation. Then, we evaluated adipogenesis by Oil Red O staining and assessed the expression patterns of adipocyte-specific fatty acid binding protein (aP2) and peroxisome proliferator-activated receptor (PPAR) gamma using real-time polymerase chain reaction methods. Our results indicated that the treatment with MSTN before or during the induction of differentiation in MSCs could both inhibit the adipogenesis. However, the treatment with MSTN only during the induction of differentiation in ADSCs could suppress the adipogenesis. Those results showed that MSTN had different roles in the adipogenesis of ADSCs and MSCs. It can shed new light on the origin of adipocyte located in muscle. PMID- 22081443 TI - The role of diffusion tensor imaging in the study of cognitive aging. AB - This chapter gives an overview of the role that diffusion tensor MRI (DTI) can play in the study of cognitive decline that is associated with advancing age. A brief overview of biological injury processes that impinge on the aging brain is provided, and their overall effect on the integrity of neural architecture is described. Cognitive decline associated with aging, and white matter connectivity degradation as a biological substrate for that decline, is then described. We then briefly describe the technology of DTI as a means for in vivo, non-invasive interrogation of white matter connectivity, and relate it to FLAIR, a more traditional MRI method for assessing white matter injury. We then survey the existing findings on relationships between aging-associated neuropathological processes and DTI measurements on one hand; and relationships between DTI measurements and late-life cognitive function on the other. We conclude with a summary of current research directions in relation to DTI studies of cognitive aging. PMID- 22081445 TI - Prognostic significance of CD56 antigen expression in patients with acute myeloid leukemia. AB - The aims of this study were to investigate the frequency and prognostic relevance of CD56 expression in patients with acute myeloid leukemia (AML) and to compare the importance of CD56 expression with standard prognostic factors, such as age, leukocytosis, cytogenetic abnormalities and performance status. We analyzed the data of 184 newly diagnosed patients with non-promyelocytic AML and a follow-up of 36 months. The median patient age was 58 years, with a range of 18-79. CD56+ antigen was recorded in 40 patients (21.7%). CD56 + was the most significant risk factor for OS: P = 0.05. The most significant factor for a poor rate of CR was age >= 55 years (P = 0.001). CD56 positivity had no significant influence on CR rate, but it was the most significant risk factor for disease-free survival (P = 0.005). The CD56 antigen is an independent prognostic risk factor, and its presence should be measured regularly for a better prognostic assessment of patients with AML. PMID- 22081446 TI - Computed tomography scanning facilitates the diagnosis of sacroiliitis in patients with suspected spondylarthritis: results of a prospective multicenter French cohort study. AB - OBJECTIVE: To assess the performance of computed tomography (CT) scanning for ascertaining sacroiliitis in patients with suspected spondylarthritis (SpA). METHODS: The Echography in Spondylarthritis French cohort consists of 489 patients with suspected SpA. At baseline, all patients underwent clinical examination, HLA-B typing, and pelvic radiography. Pelvic CT scanning was performed if sacroiliitis on radiography was considered uncertain or if patients presented with buttock pain duration of >6 months. A set of 100 paired radiographs and CT scans was read in a blinded manner by 2 radiologists, and the kappa coefficient was used to assess their interreader reliability. One of the radiologists read the 173 available pairs of radiographs and CT scans performed at baseline. RESULTS: After training, interreader reliability was moderate for sacroiliitis grading on radiographs (kappa = 0.59), excellent on CT scans (kappa = 0.91), and excellent for ascertaining sacroiliitis on both radiographs (kappa = 1) and CT scans (kappa = 0.96). The first and second readers considered the quality of imaging to be excellent in 66% and 67%, respectively, of the radiographs (kappa = 0.88) and in 93% and 92%, respectively, of the CT scans (kappa = 0.93). Concordance between radiographs and CT scans was low for sacroiliitis grading (kappa = 0.08) or ascertainment (kappa = 0.16). Definite sacroiliitis was ascertained on radiographs in 6 patients (3.5%) (confirmed by CT scans in 4 patients) and on CT scans in 32 patients (18.5%). A history of uveitis was associated with definite sacroiliitis on radiographs (P = 0.04) and CT scans (P < 0.0001). CONCLUSION: Definite sacroiliitis was underestimated by radiography, as compared to CT scanning. CT scanning should facilitate the diagnosis of ankylosing spondylitis in patients with suspected SpA. PMID- 22081447 TI - Robust discrimination of glioblastomas from metastatic brain tumors on the basis of single-voxel (1)H MRS. AB - This article investigates methods for the accurate and robust differentiation of metastases from glioblastomas on the basis of single-voxel (1)H MRS information. Single-voxel (1)H MR spectra from a total of 109 patients (78 glioblastomas and 31 metastases) from the multicenter, international INTERPRET database, plus a test set of 40 patients (30 glioblastomas and 10 metastases) from three different centers in the Barcelona (Spain) metropolitan area, were analyzed using a robust method for feature (spectral frequency) selection coupled with a linear-in-the parameters single-layer perceptron classifier. For the test set, a parsimonious selection of five frequencies yielded an area under the receiver operating characteristic curve of 0.86, and an area under the convex hull of the receiver operating characteristic curve of 0.91. Moreover, these accurate results for the discrimination between glioblastomas and metastases were obtained using a small number of frequencies that are amenable to metabolic interpretation, which should ease their use as diagnostic markers. Importantly, the prediction can be expressed as a simple formula based on a linear combination of these frequencies. As a result, new cases could be straightforwardly predicted by integrating this formula into a computer-based medical decision support system. This work also shows that the combination of spectra acquired at different TEs (short TE, 20-32 ms; long TE, 135-144 ms) is key to the successful discrimination between glioblastomas and metastases from single-voxel (1)H MRS. PMID- 22081449 TI - Fair and just or just fair? Examining models of government--not-for-profit engagement under the Australian Social Inclusion Agenda. AB - This paper explores the interrelationship between two contemporary policy debates: one focused on the social determinants of health and the other on social (inclusion) policy within contemporary welfare regimes. In both debates, academics and policy makers alike are grappling with the balance between universal and targeted policy initiatives and the role of local 'delivery' organizations in promoting health and social equality. In this paper, we discuss these debates in the context of a recent social policy initiative in Australia: the Social Inclusion Agenda. We examine two proposed models of engagement between the government and the not-for-profit welfare sector for the delivery of social services. We conclude that the two models of engagement currently under consideration by the Australian government have substantially different outcomes for the health of disadvantaged communities and the creation of a more socially inclusive Australia. PMID- 22081448 TI - beta-Catenin determines upper airway progenitor cell fate and preinvasive squamous lung cancer progression by modulating epithelial-mesenchymal transition. AB - Human lung cancers, including squamous cell carcinoma (SCC) are a leading cause of death and, whilst evidence suggests that basal stem cells drive SCC initiation and progression, the mechanisms regulating these processes remain unknown. In this study we show that beta-catenin signalling regulates basal progenitor cell fate and subsequent SCC progression. In a cohort of preinvasive SCCs we established that elevated basal cell beta-catenin signalling is positively associated with increased disease severity, epithelial proliferation and reduced intercellular adhesiveness. We demonstrate that transgene-mediated beta-catenin inhibition within keratin 14-expressing basal cells delayed normal airway repair while basal cell-specific beta-catenin activation increased cell proliferation, directed differentiation and promoted elements of early epithelial-mesenchymal transition (EMT), including increased Snail transcription and reduced E-cadherin expression. These observations are recapitulated in normal human bronchial epithelial cells in vitro following both pharmacological beta-catenin activation and E-cadherin inhibition, and mirrored our findings in preinvasive SCCs. Overall, the data show that airway basal cell beta-catenin determines cell fate and its mis-expression is associated with the development of human lung cancer. PMID- 22081450 TI - Hemosiderin-containing plasma cells. PMID- 22081451 TI - The role of atomic level steric effects and attractive forces in protein folding. AB - Protein folding into tertiary structures is controlled by an interplay of attractive contact interactions and steric effects. We investigate the balance between these contributions using structure-based models using an all-atom representation of the structure combined with a coarse-grained contact potential. Tertiary contact interactions between atoms are collected into a single broad attractive well between the C(beta) atoms between each residue pair in a native contact. Through the width of these contact potentials we control their tolerance for deviations from the ideal structure and the spatial range of attractive interactions. In the compact native state dominant packing constraints limit the effects of a coarse-grained contact potential. During folding, however, the broad attractive potentials allow an early collapse that starts before the native local structure is completely adopted. As a consequence the folding transition is broadened and the free energy barrier is decreased. Eventually two-state folding behavior is lost completely for systems with very broad attractive potentials. The stabilization of native-like residue interactions in non-perfect geometries early in the folding process frequently leads to structural traps. Global mirror images are a notable example. These traps are penalized by the details of the repulsive interactions only after further collapse. Successful folding to the native state requires simultaneous guidance from both attractive and repulsive interactions. PMID- 22081452 TI - Effect of lipopolysaccharide on alteration of phospholipids and their fatty acid composition in spleen and thymus by in vitro metabolic labeling. AB - Lipopolysaccharide (LPS) is an endotoxin, a potent stimulator of immune response and induction of LPS leads to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). ARDS is a life-threatening disease worldwide with a high mortality rate. The immunological effect of LPS with spleen and thymus is well documented; however the impact on membrane phospholipid during endotoxemia has not yet been studied. Hence we aimed to investigate the influence of LPS on spleen and thymus phospholipid and fatty acid composition by [(32) P]orthophosphate labeling in rats. The in vitro labeling was carried out with phosphate-free medium (saline). Time course, LPS concentration-dependent, pre- and post-labeling with LPS and fatty acid analysis of phospholipid were performed. Labeling studies showed that 50 ug LPS specifically altered the major phospholipids, phosphatidylcholine and phosphatidylglycerol in spleen and phosphatidylcholine in thymus. Fatty acid analysis showed a marked alteration of unsaturated fatty acids/saturated fatty acids in spleen and thymus leading to immune impairment via the fatty acid remodeling pathway. Our present in vitro lipid metabolic labeling study could open up new vistas for exploring LPS-induced immune impairment in spleen and thymus, as well as the underlying mechanism. PMID- 22081453 TI - Passages 2012. PMID- 22081455 TI - Heating-induced phase transition of bupropion hydrobromide polymorphs. AB - Crystal phase transition and isothermal crystallization kinetics of bupropion hydrobromide is studied by thermal analysis, X-ray powder diffractometry, and scanning electron microscopy. As well known, bupropion hydrobromide has two stable polymorphic forms, form I and form II, during the production. Here it is found that form II will convert into form I with thermal treatment. Avrami exponent n is evaluated to be around 2.0 in the range 170 degrees C-190 degrees C, which indicates that the phase transition is a process of one-dimensional nucleation growth. This viewpoint is also confirmed by microscope morphology study. In addition, phase-transition active energy is calculated to be 239.4 kJ/mol, which means that a high energy barrier needs to be overcome to start up the phase transition. PMID- 22081456 TI - The agreement of left ventricular function parameters between (99m)Tc-tetrofosmin gated myocardial SPECT and gated myocardial MRI. AB - OBJECTIVE: The aim is to compare and evaluate the agreement of quantification of left ventricular functional parameters obtained by two different methods, (99m)Tc tetrofosmin gated myocardial perfusion SPECT (MPS) and cardiac magnetic resonance imaging (CMR). METHODS: Ten healthy male volunteers participated. Gated MPS data were acquired using 32 frames, which were also combined into 16- and 8-frame data set for the investigation. Gated CMR data were acquired using 8, 16 and 32-frame for the different sets. All examinations were conducted in resting and at exercise conditions. Quantitative measurements of end-diastolic volume (EDV), end systolic volume (ESV), left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR) and time to peak filling (TTPF) were done for each study, respectively. Finally, we evaluated the concordance of parameters between gated MPS and gated CMR by % difference and Bland-Altman plot analysis. RESULTS: LVEF showed favorable concordance in both rest and exercise conditions (% differences were around 10%). PER, PFR and TTPF also showed good concordances in rest conditions, under 32-frame gated collections particularly (% differences were around 10%). In exercise conditions, although the concordances were relatively good, certain variances were noted (% differences were around 20-25%). Regarding left ventricular volumes, the concordance were worse in both conditions (% differences were around 30-40%). CONCLUSIONS: In quantifying of left ventricular function parameter, gated CMR provides similar quantitative values comparing with gated MPS except for ventricular volumes in rest conditions. In contrast, there were certain variations except for LVEF in exercised examinations. When we follow patients by the same cardiac parameters with CMR and MPS, using parameters across the two modalities proved to be possible under rest condition. However, it is limited at exercise condition. PMID- 22081457 TI - A nuclear power plant accident in Fukushima: what should we do? PMID- 22081459 TI - A multicenter phase II study of darinaparsin in relapsed or refractory Hodgkin's and non-Hodgkin's lymphoma. PMID- 22081458 TI - Solution versus gas-phase modification of peptide cations with NHS-ester reagents. AB - A comparison between solution and gas phase modification of primary amine sites in model peptide cations with N-hydroxysuccinimide (NHS) ester reagents is presented. In all peptides, the site of modification in solution was directed to the N-terminus by conducting reactions at pH=5, whereas for the same peptides, a lysine residue was preferentially modified in the gas phase. The difference in pKa values of the N-terminus and epsilon-amino group of the lysine allows for a degree of control over sites of protonation of the peptides in aqueous solution. With removal of the dielectric and multiple charging of the peptide ions in the gas phase, the accommodation of excess charge can affect the preferred sites of reaction. Interaction of the lone pair of the primary nitrogen with a proton reduces its nucleophilicity and, as a result, its reactivity towards NHS-esters. While no evidence for reaction of the N-terminus with sulfo-NHS-acetate was noted in the model peptide cations, a charge inversion experiment using bis[sulfosuccinimidyl] suberate, a cross-linking reagent with two sulfo-NHS-ester functionalities, showed modification of the N-terminus. Hence, an unprotonated N terminus can serve as a nucleophile to displace NHS, which suggests that its lack of reactivity with the peptide cations is likely due to the participation of the N-terminus in solvating excess charge. PMID- 22081461 TI - An unusual case of lumbar paravertebral miositis ossificans mimicking muscular skeletal tumor. AB - Several lesions have clinical and radiological characteristics mimicking muscular skeletal tumor. Myositis ossificans usually presents a typical pattern making biopsy unnecessary; nevertheless, in rare cases, neoplasm must be ruled out. Biopsy is often sufficient to allow a diagnosis and a correct related treatment, but, unfortunately, sometimes it may lead to erroneous treatment. We report an unusual case of a lumbar paravertebral mass that had an MRI aspect similar to a chondrosarcoma, a histology pattern based on biopsy compatible with neurinoma and a definitive diagnosis of myosistis ossificans. PMID- 22081462 TI - [The reception of the PPmP by readers and scientists]. PMID- 22081463 TI - [Developmental psychopathology of narcissistic disorders]. AB - For the development of pathological narcissism, personality traits - partially genetically caused and derived from childhood experiences - play an important role. Current studies on the developmental psychopathology of narcissistic disorders are discussed with reference to the development of the self in children. Different developmental pathways underlie the grandiose (overt) and the vulnerable (covert) type of narcissistic disorders which are shown in 2 possible models. In these models parental admiration and coldness as well as dominant and manipulative behaviour lead to an overt subtype of narcissism, the experience of maltreatment and an increased sensitivity for negative experiences lead to a covert subtype of narcissism. PMID- 22081464 TI - [Psychological complaints by academic level among students seeking counseling]. AB - There is a lack of detailed surveys on the mental health of students. German university counseling centers have faced increasing demand, which is primarily due to the newly introduced Bachelor/Master system. The data of 251 students who consulted the Leipzig psychotherapeutic counseling center were examined with regard to complaints, symptoms and interpersonal problems. Significant differences were observed with respect to usage of the counseling center and interpersonal problems. Master's degree and state examination candidates sought counsel most often. Bachelor's degree students were least likely to seek help. Magister and Bachelor candidates showed a higher level of symptoms and interpersonal problems. Depression and work disruptions were the concerns mentioned most frequently. The findings should be examined further using additional samples. It should be clarified whether the likelihood of usage also differs with other forms of psychological help. PMID- 22081465 TI - [Assessment of communication skills with an OSCE among first year medical students]. AB - In order to determine if first year medical students of a Medical Psychology and Medical Sociology course have adopted basic physician patient communication skills, we developed an appropriate Objective Structured Clinical Examination (OSCE). The parcours took place in a pretest condition (n=182) and in the following semester under test condition, now relevant for passing the course (n=181). Reliability of the OSCE reached a medium degree (alpha=0.55/0.50). Results of written examinations and OSCE scores were weakly correlated. The correlation between task competence and patient-centeredness was higher in the pretest than under test condition. Female students mostly achieved higher scores than male students. Nearly all of the students (92%/97%) were in favor of continuing this examination. Physician-patient communication is a process of high complexity, but it can be tested by OSCE. Relevance for passing the course seems to enhance the learning behaviour. PMID- 22081466 TI - [Prevalence, comorbidity and severity of psychosomatic disorders in outpatients with Turkish migration background]. AB - In this study the prevalence and comorbidity of mental disorders were examined for the first time with the Structured Clinical Interview for DSM-IV (SCID-I) in a consecutive sample of Turkish speaking patients (n=51). The symptom severity of the depressiveness was measured with the Beck Depression Inventory (BDI), of the somatoform complaints with the Screening for Somatoform Symptoms (SOMS) and of the posttraumatic stress disorder (PTSD) with the Essen Trauma Inventory (ETI). The most common current diagnoses were the somatization disorder (41.2%; n=21), a single episode of major depression (37.3%; n=19) and the PTSD (31.4%; n=16). In 80.4% (n=41) of the patients at least one comorbid mental disorder was documented. In comparison with German reference values the Turkish patients showed a significant higher severity of the depressive and posttraumatic, however not of the somatoform symptomatology. PMID- 22081467 TI - [Diagnostic accuracy of the McLean Screening Instrument for borderline personality disorder in an inpatient sample who seek a disorder-specific treatment]. AB - Borderline personality disorder (BPD) is considered as the most prevalent personality disorder in an inpatient setting. The McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) was developed to identify individuals with BPD reliably, valid and economically. To examine the discriminatory ability and diagnostic efficiency of the German version of the MSI-BPD in a sample with patients who meet probable BPD and seek a disorder-related inpatient treatment program. Based on a sample (N=298) containing 178 BPD-patients (60%), the area under the curve was AUC=0.70 (CI 95%: 0.647. 84% of individuals with BPD (sensitivity) and 39% of individuals without BPD were identified correctly (specificity). Results suggest that a self rated screening measure as the MSI-BPD should not be used in a sample with patients who meet probable BPD. PMID- 22081468 TI - [Goodbye to the single sided test]. PMID- 22081469 TI - [Interdisciplinary training course Psychocardiology in primary care]. PMID- 22081470 TI - The excess burden of osteoarthritis in the province of Ontario, Canada. AB - OBJECTIVE: Little is known about the burden of osteoarthritis (OA) in Canada. This study was undertaken to estimate the excess burden of OA in Ontario, the largest province in Canada. METHODS: The records of Ontarian respondents to the Canadian Community Health Survey (CCHS) who provided consent to data linkage were linked to the Ontario Health Insurance Program physician claims database and the Discharge Abstract Database Inpatient and Day Procedure databases. Patients with OA (n = 1,474) were identified using CCHS 1.1 and the physician claims database. To determine the excess burden of OA, a control group matched by age, sex, and rural/urban status was created, with 3 controls per case (n = 4,422). Sociodemographic and medical characteristics, health-related quality of life, and 1-year physician, day (outpatient) procedure, and hospitalization costs were compared between the 2 groups. Regression analyses were performed to identify predictors of medical characteristics, health utility, and cost. RESULTS: The mean age of the OA patients and the control subjects was 66 years, and 74% of all study subjects were women. Several differences were observed between patients with OA and subjects without OA in terms of socioeconomic and medical characteristics. On a scale of 0-1, the mean utility value associated with OA was 0.68, compared to 0.84 for the control group (P < 0.0001), representing a utility decrement of 0.16. The 1-year physician, outpatient procedure, and hospitalization costs were significantly higher in the OA group than in the non OA group ($2,233 Canadian versus $1,033 Canadian, respectively; P < 0.0001). CONCLUSION: These results indicate that the excess burden of OA in Ontario is considerable. PMID- 22081471 TI - The effect of an educational intervention on meperidine use in Nova Scotia, Canada: a time series analysis. AB - PURPOSE: To evaluate the impact of a prescriber focused individual educational and audit-feedback intervention undertaken by the Nova Scotia Prescription Monitoring Program (NSPMP) in March/April 2007 to reduce meperidine use. METHOD: The NSPMP records all prescriptions for controlled substances dispensed in community pharmacies in Nova Scotia, Canada. Oral meperidine use from 1 July 2005 to 31 December 2009 was examined using NSPMP data. Monthly totals for the following were obtained: number of individual patients who filled at least one meperidine prescription, number of prescriptions, and number of tablets dispensed. Data were analyzed graphically to observe overall trends. The intervention effect was estimated on the logarithmic scale with autocorrelations over time modeled by an integrated autoregressive moving average model for each outcome measure. RESULTS: An overall trend toward decreasing use from July 2005 to December 2009 was apparent for all three outcome measures. The intervention was associated with a statistically significant reduction in meperidine use, after adjusting for the overall long-term trend. Compared with the pre intervention period, the monthly number of patients declined by 12% (p < 0.001; 95% confidence interval [CI] = 5%-18%), prescriptions by 10% (p < 0.001; 95%CI = 3%-17%), and tablets by 13.5% (p < 0.001, 95%CI = 6%-29%) in the post intervention period. CONCLUSION: Given the risks associated with meperidine, determining that this intervention successfully reduced meperidine use is encouraging. This study highlights the potential for using population data such as the NSPMP to evaluate the effectiveness of population-level interventions to improve medication use, including professional, organizational, financial, and regulatory initiatives. PMID- 22081472 TI - Abnormal or delayed development of the posterior membranous area of the brain: anatomy, ultrasound diagnosis, natural history and outcome of Blake's pouch cyst in the fetus. AB - OBJECTIVES: To review the normal and pathological development of the posterior membranous area (PMA) in the fetal brain, to define sonographic criteria with which to diagnose a Blake's pouch cyst (BPC) in the fetus and to review the ultrasound features, associations and outcome of 19 cases of BPC seen at our center over the last 5 years. METHODS: We conducted a MEDLINE search using the terms 'Blake's pouch', with or without 'fourth ventricle' or '4(th) ventricle', with or without 'roof' and identified articles describing normal and/or abnormal development of the PMA, whether or not they were cited in the limited clinical literature on BPC. A description of the normal and abnormal development of BPC was derived by collating these articles. The clinical retrospective study included 19 cases of posterior fossa anomalies with a final diagnosis of BPC seen at our institution. The following variables were assessed: referral indication, gestational age at diagnosis, ultrasound and magnetic resonance imaging (MRI) findings, associated anomalies, natural history and pregnancy and neonatal outcome. A transvaginal three-dimensional (3D) ultrasound examination was performed in all cases and 15 cases underwent MRI. To confirm the diagnosis, postnatal MRI, transfontanellar ultrasound or autopsy were available in all cases. RESULTS: Among the 19 cases reviewed, referral indications were: suspicion of vermian abnormality in 11 (58%) cases and other non-central nervous system anomaly in eight (42%) cases. Sonographically, all cases showed the following three signs: 1) normal anatomy and size of the vermis; 2) mild/moderate anti clockwise rotation of the vermis; 3) normal size of the cisterna magna. On 3D ultrasound, the upper wall of the cyst was clearly visible in 11/19 cases, with choroid plexuses on the superolateral margin of the cyst roof. On follow-up, the BPC had disappeared by 24-26 gestational weeks in six of the 11 cases which did not undergo termination of pregnancy (TOP), and remained unaltered until birth in the other five cases. There were associated anomalies in eight (42%) cases, in five of which this consisted of or included congenital heart disease. Karyotype was available in 14 cases, two of which were abnormal (both trisomy 21). Regarding pregnancy outcome, there were eight (42%) TOPs, two (10%) neonatal deaths and nine (48%) survivors. One neonate, in whom the BPC had disappeared by the time of birth, had obstructive hydrocephaly confirmed. Another neonate was diagnosed with Down syndrome after birth. Excluding the Down syndrome baby, neurodevelopmental outcome was normal at the time of writing in all eight cases. CONCLUSIONS: Based on our analysis of ultrasound features, we propose that for BPC to be diagnosed in a fetus the following three criteria should be fulfilled: 1) normal anatomy and size of the vermis; 2) mild/moderate anti-clockwise rotation of the vermis; 3) normal size of the cisterna magna. Furthermore, we found that BPC can undergo delayed fenestration at 24-26 weeks in more than 50% of cases. Finally, it seems that BPC shows a risk of association with extracardiac anomalies (heart defects in particular) and, to a lesser extent, trisomy 21. PMID- 22081473 TI - Yield of routine molecular analyses in colorectal cancer patients <=70 years to detect underlying Lynch syndrome. AB - Although early detection of Lynch syndrome (LS) is important, a considerable proportion of patients with LS remains unrecognized. We aimed to study the yield of LS detection by routine molecular analyses in colorectal cancer (CRC) patients until 70 years of age. We prospectively included consecutive CRC patients <=70 years. Tumour specimens were analysed for microsatellite instability (MSI), immunohistochemical mismatch-repair protein expression and MLH1-promoter methylation. Tumours were classified as either: (a) likely caused by LS; (b) sporadic microsatellite-unstable (MSI-H); or (c) microsatellite-stable (MSS). Predictors of LS were determined by multivariable logistic regression. A total of 1117 CRC patients (57% males, median age 61 years) were included. Fifty patients (4.5%, 95% CI 3.4-5.9) were likely to have LS, and 71 had a sporadic MSI-H tumour (6.4%, 95% CI 5.1-8.0). Thirty-five patients likely to have LS (70%) were aged > 50 years. A molecular profile compatible with LS was detected in 10% (15/144) of patients aged <=50, in 4% (15/377) of those aged 51-60 and in 3% (20/596) of patients > 61 years. Compared to MSS cases, patients likely to have LS were significantly younger (OR 3.9, 95% CI 1.7-8.7) and more often had right-sided CRCs (OR 14, 95% CI 6.0-34). In conclusion, molecular screening for LS in CRC patients <=70 years leads to identification of a molecular profile compatible with LS in 4.5% of patients, with most of them not fulfilling the age criterion (<=50 years) routinely used for LS assessment. Routine use of MSI testing may be considered in CRC patients up to the age of 70 years, with a central role for the pathologist in the selection of patients. PMID- 22081474 TI - Scheduled infliximab monotherapy to prevent recurrence of Crohn's disease following ileocolic or ileal resection: a 3-year prospective randomized open trial. AB - BACKGROUND: Infliximab (IFX) is effective for remission induction and maintenance of Crohn's disease (CD). This trial assessed the efficacy of scheduled maintenance IFX monotherapy to prevent postoperative CD recurrence. METHODS: Thirty-one CD patients who had ileocolic resection within the past 4 weeks were randomly assigned to scheduled IFX at 5 mg/kg intravenously every 8 weeks for 36 months (n = 15) or without IFX (control, n = 16). All patients were treated without immunomodulator or corticosteroid following surgery. The primary and secondary endpoints were remission rates at 12 and 36 months, defined as CD Activity Index (CDAI) <=150, an International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score <2, and C-reactive protein (CRP) <0.3 mg/dL. Additionally, endoscopic recurrences at 12 and 36 months were evaluated. RESULTS: At 12 and 36 months, 100%, and 93.3% of patients in the IFX group were in remission (IOIBD <2), respectively vs. 68.8% and 56.3% in the control arm (P < 0.03). Similarly, 86.7% and 86.7% of patients in the IFX group maintained serological remission (CRP <0.3 mg/dL) vs. 37.5% and 37.5% in the control arm (P < 0.02). Further, the IFX group achieved higher endoscopic remission at 12 months, 78.6% vs. 18.8% (P = 0.004). However, in the Kaplan-Meier survival analysis the CDAI scores between the two arms were not significantly different either at 12 or at 36 months. No adverse event (AE) was observed. CONCLUSIONS: An early intervention with IFX monotherapy should prevent clinical, serological, and endoscopic CD recurrence following ileocolic resection. Thiopurine naivety and eliminating the initial loading dose of IFX might minimize serious AEs. PMID- 22081475 TI - Systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease: a case review. PMID- 22081476 TI - A temperature-dependent conformational change of NADH oxidase from Thermus thermophilus HB8. AB - Using molecular dynamics simulations and steady-state fluorescence spectroscopy, we have identified a conformational change in the active site of a thermophilic flavoenzyme, NADH oxidase from Thermus thermophilus HB8 (NOX). The enzyme's far UV circular dichroism spectrum, intrinsic tryptophan fluorescence, and apparent molecular weight measured by dynamic light scattering varied little between 25 and 75 degrees C. However, the fluorescence of the tightly bound FAD cofactor increased approximately fourfold over this temperature range. This effect appears not to be due to aggregation, unfolding, cofactor dissociation, or changes in quaternary structure. We therefore attribute the change in flavin fluorescence to a temperature-dependent conformational change involving the NOX active site. Molecular dynamics simulations and the effects of mutating aromatic residues near the flavin suggest that the change in fluorescence results from a decrease in quenching by electron transfer from tyrosine 137 to the flavin. PMID- 22081477 TI - Cloning and extracellular expression of inulin fructotransferase from Arthrobacter aurescens SK 8.001 in E. coli. AB - BACKGROUND: Difructose anhydride (DFA) III is a natural and low-calorie sweetener. It stimulates the absorption of calcium and other minerals. Inulin fructotransferase (IFTase; EC 4.2.2.18), catalysing inulin hydrolysis to DFA III, is considered to be the most promising enzyme for the production of DFA III. RESULTS: IFTase gene from Arthrobacter aurescens SK 8.001 was cloned and sequenced. Transformant with native IFTase signal peptide was a useful system for extracellular over-expression of IFTase, and its extracellular IFTase activity reached 81.0 U mL(-1) . This value was 4.1-fold of that obtained with A. aurescens SK 8.001 for IFTase production. The recombinant IFTase was purified to electrophoretical homogeneity and characterized. The enzyme showed maximum activity at pH 6.0 and 55 degrees C, and retained 81.3% of its initial activity after incubation at 60 degrees C for 4 h. CONCLUSION: IFTase gene from A. aurescens SK 8.001 was cloned, sequenced and over-expressed in E. coli. IFTase was reported for the first time to be over-expressed extracellularly. The recombinant IFTase was purified and characterized, and shown to be a good candidate for potential application in DFA III production. PMID- 22081478 TI - Novel furosemide cocrystals and selection of high solubility drug forms. AB - Furosemide was screened in cocrystallization experiments with pharmaceutically acceptable coformer molecules to discover cocrystals of improved physicochemical properties, that is high solubility and good stability. Eight novel equimolar cocrystals of furosemide were obtained by liquid-assisted grinding with (i) caffeine, (ii) urea, (iii) p-aminobenzoic acid, (iv) acetamide, (v) nicotinamide, (vi) isonicotinamide, (vii) adenine, and (viii) cytosine. The product crystalline phases were characterized by powder x-ray diffraction, differential scanning calorimetry, infrared, Raman, near IR, and (13) C solid-state NMR spectroscopy. Furosemide-caffeine was characterized as a neutral cocrystal and furosemide cytosine an ionic salt by single crystal x-ray diffraction. The stability of furosemide-caffeine, furosemide-adenine, and furosemide-cytosine was comparable to the reference drug in 10% ethanol-water slurry; there was no evidence of dissociation of the cocrystal to furosemide for up to 48 h. The other five cocrystals transformed to furosemide within 24 h. The solubility order for the stable forms is furosemide-cytosine > furosemide-adenine > furosemide-caffeine, and their solubilities are approximately 11-, 7-, and 6-fold higher than furosemide. The dissolution rates of furosemide cocrystals were about two times faster than the pure drug. Three novel furosemide compounds of higher solubility and good phase stability were identified in a solid form screen. PMID- 22081479 TI - A structural and functional dissection of the cardiac stress response factor MS1. AB - MS1 is a protein predominantly expressed in cardiac and skeletal muscle that is upregulated in response to stress and contributes to development of hypertrophy. In the aortic banding model of left ventricular hypertrophy, its cardiac expression was significantly upregulated within 1 h. Its function is postulated to depend on its F-actin binding ability, located to the C-terminal half of the protein, which promotes stabilization of F-actin in the cell thus releasing myocardin-related transcription factors to the nucleus where they stimulate transcription in cooperation with serum response factor. Initial attempts to purify the protein only resulted in heavily degraded samples that showed distinct bands on SDS gels, suggesting the presence of stable domains. Using a combination of combinatorial domain hunting and sequence analysis, a set of potential domains was identified. The C-terminal half of the protein actually contains two independent F-actin binding domains. The most C-terminal fragment (294-375), named actin binding domain 2 (ABD2), is independently folded while a proximal fragment called ABD1 (193-296) binds to F-actin with higher affinity than ABD2 (KD 2.21 +/- 0.47 MUM vs. 10.61 +/- 0.7 MUM), but is not structured by itself in solution. NMR interaction experiments show that it binds and folds in a cooperative manner to F-actin, justifying the label of domain. The architecture of the MS1 C-terminus suggests that ABD1 alone could completely fulfill the F actin binding function opening up the intriguing possibility that ABD2, despite its high level of conservation, could have developed other functions. PMID- 22081480 TI - Test of the month: The chromogenic antifactor Xa assay. AB - As the number of anticoagulant drugs increases and new ones are brought to market, the utility of the routine screening coagulation tests of today--namely the prothrombin time and activated partial thromboplastin time--will be significantly reduced in many clinical situations. Although the new anticoagulants are designed to require less frequent monitoring, it is imperative that the proper test is selected in situations where monitoring is needed. In addition, tests that are designed for the new generation of drugs may be informative in certain situations for monitoring the anticoagulants that have been in use for many years. Here, we present the chromogenic antifactor Xa assay and demonstrate its utility and its limitations in monitoring three anticoagulant drugs (unfractionated heparin, low molecular weight heparin, and fondaparinux) as well as one emerging anticoagulant, rivaroxaban. PMID- 22081481 TI - Efficacy and safety of saxagliptin in drug-naive Asian patients with type 2 diabetes mellitus: a randomized controlled trial. AB - BACKGROUND: Few studies have assessed the use of new oral anti-diabetic agents in Asian populations. This study assesses the efficacy and safety of saxagliptin versus placebo in Asian patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Five hundred sixty-eight drug-naive adult patients with T2DM and glycated haemoglobin levels (HbA(1c)) of 7.0-10.0% (53-86 mmol/mol) were randomized 1 : 1 to receive saxagliptin 5 mg daily or placebo. Efficacy endpoints included changes from baseline to week 24 in HbA(1c) , fasting plasma glucose (FPG), post-prandial glucose area under the curve from 0 to 180 min (PPG AUC(0 180)), and the proportion of patients achieving HbA(1c) <7.0% (53 mmol/mol). Adverse events (AEs) and serious AEs (SAEs) were evaluated. RESULTS: Saxagliptin provided statistically significant adjusted mean decreases from baseline to week 24 compared with placebo, respectively, in HbA(1c) (-0.84% [-9 mmol/mol] versus 0.34% [-4 mmol/mol]; p < 0.0001), FPG (-0.90 versus -0.17 mmol/L; p < 0.0001), and PPG AUC(0-180) (-417 versus -235 mmol . min/L; p = 0.0010). A significantly greater proportion of patients achieved a therapeutic glycaemic response (HbA(1c) <7.0% [53 mmol/mol]) with saxagliptin (45.8%) versus placebo (28.8%; p < 0.0001). The proportions of patients who experienced >=1 AE (excluding hypoglycaemia) was 43.3% for saxagliptin and 35.6% for placebo. Few patients in either treatment group experienced an SAE (2.8%, saxagliptin; 1.4%, placebo). A low proportion of patients reported hypoglycaemic events (1.8%, saxagliptin; 0.7%, placebo). CONCLUSIONS: Saxagliptin improved glycaemic control and was well tolerated in drug-naive Asian patients with T2DM. PMID- 22081482 TI - Exploiting sparsity to accelerate noncontrast MR angiography in the context of parallel imaging. AB - Noncontrast techniques for peripheral MR angiography are receiving renewed interest because of safety concerns about the use of gadolinium in patients with renal insufficiency. One class of techniques involves subtraction of dark-blood images acquired during fast systolic flow from bright-blood images obtained during slow diastolic flow. The goal of this work was to determine whether the inherent sparsity of the difference images could be exploited to achieve greater acceleration without loss of image quality in the context of generalized autocalibrating partially parallel acquisition (GRAPPA). It is shown that noise amplification at high acceleration factors can be reduced by performing subtraction on the raw data, before calculation of the GRAPPA weights, rather than on the final magnitude images. Use of the difference data to calculate the GRAPPA weights decreases the geometry factor (g-factor), because the difference data represent a sparse image set. This demonstrates an inherent property of GRAPPA and does not require the use of compressed sensing. Application of this approach to highly accelerated data from healthy volunteers resulted in similar depiction of large arteries to that obtained with low acceleration and standard reconstruction. However, visualization of very small vessels and arterial branches was compromised. PMID- 22081483 TI - Proteome of formalin-fixed paraffin-embedded pancreatic ductal adenocarcinoma and lymph node metastases. AB - Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related death, largely due to metastatic disease. To better understand PDAC metastatic spread and identify novel therapeutic targets, we analysed the proteome of primary tumours and matched lymph node (LN) metastases. As frozen specimens of metastatic lesions are scarce, we examined formalin-fixed paraffin-embedded (FFPE) tissues. This poses technical challenges because of the cross-linkages induced by fixation. Using laser capture microdissection (PALM system), we isolated malignant epithelia from seven FFPE primary PDAC tumours and matched LN metastases. Following dissection, samples were analysed in duplicate using Multidimensional Protein Identification Technology (MudPIT); this resulted in the identification of 1504 proteins, 854 of which were common to all samples analysed. Comparison of the obtained proteins with data from previous proteomics studies on pancreatic tissue, pancreatic juice, serum, and urine resulted in a less than 30% overlap, indicating that our study has substantially expanded the current database of proteins expressed in this malignancy. Statistical analysis further showed that 115/854 proteins (13.5%) were significantly differentially expressed (g-value >= 3.8). Two proteins, S100P and 14-3-3 sigma, with highly significant g-values were confirmed to be significantly differentially expressed (S100P: p = 0.05 and 14-3-3 sigma: p < 0.001) in a larger series of 55 cases of matched primary PDAC and LN metastases using immunohistochemistry. Thus, laser capture microdissection of FFPE tissue coupled with downstream proteomic analysis is a valid approach for the investigation of metastatic PDAC. This is the first study to establish and compare the protein composition of primary PDAC and matched LN metastases, and has resulted in the identification of several potential epithelial-specific therapeutic targets, including 14-3-3 sigma and S100P. PMID- 22081484 TI - Los(T) in long-term care: empirical evidence from German data 2000-2009. AB - Using microdata, that is, representative samples of 114,403 German long-term care dependants (LTCDs) observed from 2000 to 2009, we give a comprehensive insight into the length of stay (LOS) in long-term care (LTC). Furthermore, this paper evaluates the effects of longevity on the LOS, thus revisiting the debate on the validity of the competing theories of compression or expansion of morbidity in LTC. The analysis finds significant effects on the LOS when AGE is controlled for, albeit do not confirm the time-to-death hypothesis. However, controlling for ASSESSMENT LEVEL suggests an improved health status of LTCDs over time, thus supporting the time-to-death hypothesis. An analysis of the mortality rates of LTCDs is to give insight into the opposing results. But the regression of mortality shows a divergence in the development of mortality rates for different disability levels. This is evidence to suggest that the 'improved' health status in LTC is not only due to actual changes in the health status, but also a consequence of political intervention. PMID- 22081485 TI - First-trimester diagnosis of cleft lip and palate using three-dimensional ultrasound. AB - OBJECTIVE: To determine whether systematic examination of primary and secondary palates using three-dimensional (3D) ultrasound aids in the identification of orofacial clefts in the first trimester. METHODS: 3D datasets were acquired prospectively from women undergoing first-trimester ultrasound screening for aneuploidy. Multiplanar mode display was used for offline analysis of (1) the primary palate in the coronal plane at the base of the retronasal triangle and (2) the secondary palate by virtual navigation in the axial plane. In addition, 3D datasets from three fetuses with a cleft palate diagnosed in the first trimester were retrospectively identified and included randomly in the study group. RESULTS: A total of 240 3D datasets from 237 pregnancies (including three sets of twins), 89% of which were obtained transabdominally and 11% transvaginally, were examined independently by three operators. The quality of the 3D datasets was classified subjectively as good, fair and poor in 76%, 20% and 4% of cases, respectively. Seven fetuses had an orofacial cleft; all involved both the primary palate and the secondary palate. Using 3D offline analysis, the primary palate was classified as intact in 229 (95%), cleft in nine (4%) and indeterminate in two (1%). Seven of the nine fetuses suspected to have a cleft affecting the primary palate had the cleft confirmed at birth or at postmortem examination (false-positive rate 0.9% (2/231)). The secondary palate was classified as intact in 217 (90%), cleft in six (3%) and indeterminate in 17 (7%). Clefts of the secondary palate were confirmed in all six suspected cases and missed in one, which was diagnosed at 16 weeks. The visualization rate was affected by the quality of the 3D dataset (P < 0.001) and gestational age at evaluation (P < 0.01). CONCLUSION: In our series, all cases of clefting of the primary palate and 86% of cases involving the secondary palate were visualized using 3D ultrasound with a satisfactory false-positive rate. Virtual navigation of the fetal palate using the multiplanar mode display seems to be useful in the diagnosis of clefting in the first trimester. PMID- 22081486 TI - Facile and large-scale fabrication of anisometric particles from fibers synthesized by colloid-electrospinning. AB - A new top-down approach is proposed to form large amounts of anisometric particles. Multicompartment fibers that present different domains composed of silica nanoparticles and larger polystyrene nanoparticles are fabricated by colloid-electrospinning and are subsequently calcinated and broken. The obtained fibers containing voids are subsequently cut via sonication to yield anisometric particles. It is shown that the majority of the fibers can be broken at the voids. PMID- 22081487 TI - Retrospective analysis of weekly intravenous immunoglobulin prophylaxis versus intravenous immunoglobulin by IgG level monitoring in hematopoietic stem cell transplant recipients. AB - Patients undergoing allogeneic hematopoietic stem cell transplant (allo HCT) have a higher incidence of infections partly due to secondary hypogammaglobulinemia. We evaluated the role of IVIG in allo HCT patients who received prophylactic IVIG 200 mg/kg once weekly regardless of IgG level (Group 1, n = 115) compared with patients who received IVIG based on IgG level <400 mg/dL (Group 2, n = 114). Primary endpoints were the utilization of IVIG, incidence of veno-occlusive disease (VOD), graft-versus-host disease (GVHD), and documented infections within the first 100 days after allo HCT. Patients in both groups were similar except for a higher number of matched unrelated donor (MUD) transplants in Group 2 (62 vs. 41, P = 0.01). There were no significant differences in the incidence all grades of GVHD (55 vs. 50), VOD (2 vs. 0) or infections in the two groups except for a higher incidence of para-influenza infections in group 1 (9 vs. 0, P = 0.003) coinciding with the flu season. We recommend monthly monitoring of IgG level and replacement only if IgG level is <400 mg/dL. PMID- 22081488 TI - Compressibility of binary powder formulations: investigation and evaluation with compaction equations. AB - The purpose of this work was to investigate and evaluate the powder compressibility of binary mixtures containing a well-compressible compound (microcrystalline cellulose) and a brittle active drug (paracetamol and mefenamic acid) and its progression after a drug load increase. Drug concentration range was 0%-100% (m/m) with 10% intervals. The powder formulations were compacted to several relative densities with the Zwick material tester. The compaction force and tensile strength were fitted to several mathematical models that give representative factors for the powder compressibility. The factors k and C (Heckel and modified Heckel equation) showed mostly a nonlinear correlation with increasing drug load. The biggest drop in both factors occurred at far regions and drug load ranges. This outcome is crucial because in binary mixtures the drug load regions with higher changeover of plotted factors could be a hint for an existing percolation threshold. The susceptibility value (Leuenberger equation) showed varying values for each formulation without the expected trend of decrease for higher drug loads. The outcomes of this study showed the main challenges for good formulation design. Thus, we conclude that such mathematical plots are mandatory for a scientific evaluation and prediction of the powder compaction process. PMID- 22081489 TI - Long-term outcome of pomalidomide therapy in myelofibrosis. AB - Ninety-four Mayo Clinic patients with myelofibrosis (MF) participated in two consecutive clinical trials of pomalidomide (0.5-3.5 mg/day), with or without prednisone. Overall anemia response was 27% and increased to 53% in JAK2V617F positive patients with <10 cm palpable splenomegaly and <5% circulating blasts; response rate was 0% in mutation-negative patients with either >=10 cm splenomegaly or >=5% circulating blasts (P = 0.0001). Median duration of anemia response was 16 months. Treatment effect on splenomegaly was negligible. To date, pomalidomide therapy has been discontinued in 86 (91%) patients at a rate of 68% at 1 year and 89% at 2 years. Grade 1 sensory neuropathy developed in 4 (13%) of 30 patients treated for >=1 year. Risk-adjusted survival in pomalidomide-treated primary MF patients (n = 72) was similar to their counterparts not exposed to the drug (n = 471; P = 0.19). Long-term follow-up of pomalidomide treatment in MF reveals palliative value for a select group of patients and treatment-emergent sensory neuropathy. PMID- 22081490 TI - Clients' and therapists' views of the therapeutic alliance: similarities, differences and relationship to therapy outcome. AB - To better understand how clients' and therapists' views of the therapeutic alliance differ and overlap, this study investigated, first, the components of the alliance that are relevant to the therapy participants; second, their relationship to post-therapy outcome; and third, the relationships between participants' alliance constructs. To identify participants' views, exploratory factor analyses were performed on clients' (n = 176) and therapists' (n = 133 observations) ratings of the Working Alliance Inventory (short form), the Helping Alliance Questionnaire and the California Psychotherapy Alliance Scales and conducted both on each measure separately and on the three measures combined. The results of the separate analyses indicated in general poor correspondence between the participant-derived components and each measure's a priori constructs. Results of the joint analyses suggested that clients view the alliance in terms of six basic components (Collaborative Work Relationship, Productive Work, Active Commitment, Bond, Non-disagreement on Goals/Tasks and Confident Progress), five of which were found to predict client-rated and/or therapist-rated post-therapy outcome. Results for therapists suggested four basic components (Collaborative Work Relationship, Therapist Confidence & Dedication, Client Commitment & Confidence, Client Working Ability), of which three predicted post-therapy outcome. Findings of significant, but modest to low moderate, correlations between several client and therapist joint factors suggested that despite similarities, the therapy partners' views of the alliance differ in important ways. Compared with therapists, clients appear to place greater emphasis on helpfulness, joint participation in the work of therapy and negative signs of the alliance. Implications of these findings are discussed. KEY PRACTITIONER MESSAGE: Therapists should not assume that their views of the therapeutic relationship and therapeutic work are shared by their clients and are encouraged to seek the client's feedback. Therapists may benefit from conveying that the client's perspective on problems and relevant work is valued and that they are working with the client as a team. Therapists may need to explicitly address how the therapeutic work is helpful and conducive to desired changes. PMID- 22081493 TI - Illuminating the early signaling pathway of a fungal light-oxygen-voltage photoreceptor. AB - Circadian clocks are molecular timekeepers encountered in a wide variety of organisms, which allow to adapt the cell's metabolism and behavior to the daily and seasonal periods. Their function is regulated by light-sensing proteins, among which Vivid, a light-oxygen-voltage (LOV) sensitive domain of the fungus Neurospora crassa, constitutes one of the most prominent examples. Although the major photochemical and structural changes during the photocycle of this photosensor have been elucidated through experimental means, its signal transduction pathway is still poorly resolved at the molecular level. In this article, we show through molecular dynamics simulation that the primary steps after adduct formation involve a switch of Gln182 in vicinity of the chromophore FAD (flavin-adenine-dinucleotide), followed by a coupling between the Ibeta- and Hbeta-strands through H-bond formation between Gln182 and Asn161 as well as subsequent weakening of the H-bonding interaction between the Ibeta- and Abeta strands. These processes then induce a reorientation of the Abeta-Bbeta-loop with respect to the protein core as well as a simultaneous contraction of the partially unfolded alpha-helix onto the alpha-Abeta-linker at the Ncap. Finally, we demonstrate through additional dimer simulations that the light-induced conformational changes, observed in the monomeric case, play a decisive role in controlling the dimerization tendency of Vivid with its partner domains and that the light-state homodimer shows a much larger affinity for aggregation than the dark state. PMID- 22081494 TI - Bioactivity of short-chain aliphatic ketones against adults of the granary weevil, Sitophilus granarius (L.). AB - BACKGROUND: The granary weevil, Sitophilus granarius (L.), is one of the most damaging pests of stored grains, causing severe quantitative and qualitative losses. Sustainable control means, alternative to the commonly used fumigants and broad-spectrum contact insecticides, are urgently needed owing to legislative limits, the development of resistant insect strains and increasing consumer demand for safe food. Short-chain aliphatic ketones, known to be emitted by cereal grains and previously identified as repellents to adult granary weevils, were evaluated for their ability to disrupt insect orientation towards wheat grains and as possible natural fumigants. RESULTS: In behavioural bioassays, 2 pentanone, 2-hexanone, 2-heptanone and 2,3-butanedione significantly reduced insect orientation towards odours of wheat grains, with 2-hexanone and 2 heptanone being the most active. In fumigation tests, all compounds were effective in killing weevil adults, but they performed differently according to chemical structure, speed of action and presence of wheat grains. In the presence of grains, the highest fumigant toxicity was shown by 2-pentanone (LC(50) = 8.4 +/- 1.0 mg L(-1)) after 24 h exposure, and by 2-pentanone (LC(50) = 4.5 +/- 0.3 mg L(-1)), 2-heptanone (LC(50) = 7.1 +/- 0.3 mg L(-1) ) and 2-hexanone (LC(50) = 8.1 +/- 0.6 mg L(-1)) 1 week after the treatment end. CONCLUSION: Short-chain aliphatic ketones have potential for applications in IPM programmes for the granary weevil because of their behaviour-altering activity and fumigant toxicity. PMID- 22081495 TI - Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. AB - The mechanism of genotoxic potential of the cancer chemotherapeutic drugs amsacrine and nocodazole in mouse bone marrow was investigated using a micronucleus test complemented by fluorescence in situ hybridization assay with mouse centromeric and telomeric DNA probes. In animals treated with different doses of amsacrine (0.5-12 mg kg(-1) ), the frequencies of micronucleated polychromatic erythrocytes increased significantly after treatment with 9 and 12 mg kg(-1) . A statistically significant increase in micronuclei frequency was also detected for 75 mg kg(-1) nocodazole (two exposures, spaced 24 h apart). Both compounds caused significant suppressions of erythroblast proliferation at higher doses. Furthermore, the present study demonstrated for the first time that amsacrine has high incidences of clastogenicity and low incidences of aneugenicity whereas nocodazole has high incidences of aneugenicity and low incidences of clastogenicity during mitotic phases in vivo. The assay also showed that chromosomes can be enclosed in the micronuclei before and after centromere separation. Therefore, the clinical use of these genotoxic drugs must be weighed against the risks of the development of chromosomal aberrations in cancer patients and medical personnel exposed to drug regimens that include these chemicals. PMID- 22081496 TI - Interpretability and importance of functionals in competing risks and multistate models. AB - The basic parameters in both survival analysis and more general multistate models, including the competing risks model and the illness-death model, are the transition hazards. It is often necessary to supplement the analysis of such models with other model parameters, which are all functionals of the transition hazards. Unfortunately, not all such functionals are equally meaningful in practical contexts, even though they may be mathematically well defined. We have found it useful to check whether the functionals satisfy three simple principles, which may be used as criteria for practical interpretability. PMID- 22081497 TI - Spironolactone and colitis: increased mortality in rodents and in humans. AB - BACKGROUND: Crohn's disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an antifibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is antifibrotic in the context of intestinal inflammation. METHODS: In vitro, spironolactone repressed fibrogenesis in transforming growth factor beta (TGF-beta)-stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation-induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since inflammatory bowel disease (IBD) patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). RESULTS: Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n = 390 deaths, P < 0.0001). In patients without liver disease, the adjusted odds ratio (OR) for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% confidence interval [CI]: 1.51-2.63) In contrast to the main effect of spironolactone mortality, multivariate modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted OR for mortality after CDI was 1.96 (95% CI: 1.50-2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82-2.00) for patients with liver disease on spironolactone when compared to a reference group without liver disease or spironolactone use. CONCLUSIONS: We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2-fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the U.S. PMID- 22081498 TI - Factors influencing bolus dwell times in healthy older adults assessed endoscopically. AB - OBJECTIVES/HYPOTHESIS: Scant data exist on normal bolus dwell time assessed during flexible endoscopic evaluation of swallowing (FEES). The purpose of this study was to examine bolus dwell time in healthy older adults. Because it has been previously reported that some healthy older adults aspirate, we also sought to determine if bolus dwell time varied as a function of aspiration status. STUDY DESIGN: Prospective. METHODS: Seventy-six healthy volunteers from the seventh, eighth, and ninth decades of life participated. Dwell times were analyzed via FEES as a function of pharyngeal location, liquid type, delivery method, puree type, viscosity, age, and gender. RESULTS: Longer dwell times were evidenced with the eldest participants, straw delivery, and the smallest volume. Adults in the ninth decade were 4.8 (P = .01) and 3.8 (P = .02) times more likely to have longer dwell times at the vallecula and 7.1 (P = .002) and 3.8 (P = 0.02) at the pyriform sinus than those in the seventh and eighth decades, respectively. Longer dwell times at the vallecula and pyriform sinuses were 2 and 2.38 times (P < .0001) more likely for straw than cup delivery, respectively. Boluses of 5 mL were 1.5 times (P < .05) more likely to result in longer dwell times than larger volumes. Bolus dwell times did not significantly differ as a function of aspiration status. CONCLUSIONS: Advanced age, straw delivery, and small volumes yielded longer dwell times. These variables should be considered before diagnosing an abnormal bolus dwell time in elder patients. PMID- 22081499 TI - Immunoregulatory defect in patients with active Crohn's disease. PMID- 22081500 TI - Neuropathology of sporadic Parkinson's disease: evaluation and changes of concepts. AB - Parkinson's disease (PD), one of the most frequent neurodegenerative disorders, is no longer considered a complex motor disorder characterized by extrapyramidal symptoms, but a progressive multisystem or-more correctly-multiorgan disease with variegated neurological and nonmotor deficiencies. It is morphologically featured not only by the degeneration of the dopaminergic nigrostriatal system, responsible for the core motor deficits, but by multifocal involvement of the central, peripheral and autonomic nervous system and other organs associated with widespread occurrence of Lewy bodies and dystrophic Lewy neurites. This results from deposition of abnormal alpha-synuclein (alphaSyn), the major protein marker of PD, and other synucleinopathies. Recent research has improved both the clinical and neuropathological diagnostic criteria of PD; it has further provided insights into the development and staging of alphaSyn and Lewy pathologies and has been useful in understanding the pathogenesis of PD. However, many challenges remain, for example, the role of Lewy bodies and the neurobiology of axons in the course of neurodegeneration, the relation between alphaSyn, Lewy pathology, and clinical deficits, as well as the interaction between alphaSyn and other pathologic proteins. Although genetic and experimental models have contributed to exploring the causes, pathomechanisms, and treatment options of PD, there is still a lack of an optimal animal model, and the etiology of this devastating disease is far from being elucidated. PMID- 22081501 TI - Solid dispersions of alpha-mangostin improve its aqueous solubility through self assembly of nanomicelles. AB - alpha-Mangostin is an oxygenated heterocyclic xanthone with remarkable pharmacological properties, but poor aqueous solubility and low oral bioavailability hinder its therapeutic application. This study sought to improve the compound's solubility and study the mechanism underlying solubility enhancement. Solid dispersions of alpha-mangostin were prepared in polyvinylpyrrolidone (PVP) by solvent evaporation method and showed substantial enhancement of alpha-mangostin's solubility from 0.2 +/- 0.2 MUg/mL to 2743 +/- 11 MUg/mL. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated interaction between alpha-mangostin and PVP. Transmission electron microscopy and dynamic light scattering showed self-assembly of round anionic nanomicelles with particle size in the range 99-127 nm. Powder X-ray diffraction indicated conversion of alpha-mangostin from crystalline into amorphous state, and scanning electron microscopy showed the presence of highly porous powder. Studies using the fluorescent probe pyrene showed that the critical micellar concentration is about 77.4 +/- 4 MUg/mL. Cellular uptake of nanomicelles was found to be mediated via endocytosis and indicated intracellular delivery of alpha-mangostin associated with potent cytotoxicity (median inhibitory concentration of 8.9 +/- 0.2 MUg/mL). Improved solubility, self assembly of nanomicelles, and intracellular delivery through endocytosis may enhance the pharmacological properties of alpha-mangostin, particularly antitumor efficacy. PMID- 22081502 TI - Novel 3D hexapod computer-assisted orthopaedic surgery system for closed diaphyseal fracture reduction. AB - BACKGROUND: Long-bone fractures are very common in trauma centers. The conventional Arbeitsgemeindschaft fur Osteosynthesefragen (AO) technique contributes to most fracture healing problems, and external fixation technology also has several disadvantages, so new techniques are being explored. METHOD: A novel hexapod computer-assisted fracture reduction system based on a 3D-CT image reconstruction process is presented for closed reduction of long-bone diaphyseal fractures. A new reduction technique and upgraded reduction device are described and the whole system has been validated. RESULTS: Ten bovine femoral fracture models were used with random fracture patterns. Tests results were as follows: residual deviation 1.24 + 0.65 mm for the axial deflection, 1.19 + 0.37 mm for the translation, 2.34 + 1.79 degrees for the angulation, and 2.83 + 0.9 degrees for the rotation. CONCLUSION: The reduction mechanism has the advantages of high positioning, reduction and computer accuracy, and intra-operative stability for both patients and surgical team. With further investigation, it could be applied in many kinds of long-bone diaphyseal fractures. PMID- 22081503 TI - Determination of salbutamol and salbutamol glucuronide in human urine by means of liquid chromatography-tandem mass spectrometry. AB - The determination of salbutamol and its glucuronide in human urine following the inhalative and oral administration of therapeutic doses of salbutamol preparations was performed by means of direct urine injection utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) and employing d(3)-salbutamol and d(3)-salbutamol glucuronide as internal standards. Unconjugated salbutamol was detected in all administration study urine samples. Salbutamol concentrations following inhalation were commonly (99%) below 1000 ng/ml whereas values after oral administration frequently (48%) exceeded this threshold. While salbutamol glucuronide was not detected in urine samples collected after inhalation of the drug, 26 out of 82 specimens obtained after oral application contained salbutamol glucuronide with a peak value of 63 ng/ml. The percentage of salbutamol glucuronide compared to unconjugated salbutamol was less than 3%. Authentic doping control urine samples indicating screening results for salbutamol less than 1000 ng/ml, showed salbutamol glucuronide concentrations between 2 and 6 ng/ml, whereas adverse analytical findings resulting from salbutamol levels higher than 1000 ng/ml, had salbutamol glucuronide values between 8 and 15 ng/ml. The approach enabled the rapid determination of salbutamol and its glucuronic acid conjugate in human urine and represents an alternative to existing procedures since time-consuming hydrolysis or derivatization steps were omitted. Moreover, the excretion of salbutamol glucuronide in human urine following the administration of salbutamol was proven. PMID- 22081504 TI - FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer. AB - To characterize the pattern of ETS rearrangements and to uncover novel ETS fusion genes, we analyzed 200 prostate carcinomas (PCa) with TaqMan low-density arrays (TLDAs), followed by selective analyses with fluorescence in situ hybridization (FISH), RT-PCR, and sequencing. Besides confirming the recurrent presence of ERG, ETV1, ETV4, and ETV5 rearrangements, we here report FLI1 as the fifth ETS transcription factor involved in fusion genes in prostate cancer. Outlier expression of the FLI1 gene was detected by TLDAs in one PCa that showed relative overexpression of FLI1 exons 4:5 as compared with FLI1 exons 2:3. A structural rearrangement was found using FISH probes flanking the FLI1 gene and RT-PCR and sequencing analyses showed fusion of SLC45A3 exon 1 with FLI1 exon 3. Interestingly, we found four cases with two different ETS rearrangements in the index tumor, thus revealing intratumor genetic heterogeneity. Correlation analysis with clinico-pathological data showed association of ERG rearrangements with locally advanced disease (pT3, P = 0.007) and MYC overexpression (P = 0.001), and association of ETV1 rearrangements with PTEN downregulation (P = 0.015). We report that FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer and that intratumor genetic heterogeneity of ETS rearrangements can occasionally be found in index primary tumors. PMID- 22081506 TI - Tunable lasing from a cholesteric liquid crystal film embedded with a liquid crystal nanopore network. AB - Continuous tuning of lasing wavelength is achieved in cholesteric liquid crystal lasers by embedding a network of nanopores with an average size of 10 nm filled with liquid crystals inside a polymerized matrix with helical order. The device possesses both high transparency and a fast response time because the tuning is driven by local reorientation of the liquid crystal molecules in the nanopores. PMID- 22081505 TI - Traumatic stress in acute leukemia. AB - OBJECTIVE: Acute leukemia is a condition with an acute onset that is associated with considerable morbidity and mortality. However, the psychological impact of this life-threatening condition and its intensive treatment has not been systematically examined. In the present study, we investigate the prevalence and correlates of post-traumatic stress symptoms in this population. METHODS: Patients with acute myeloid, lymphocytic, and promyelocytic leukemia who were newly diagnosed, recently relapsed, or treatment failures were recruited at a comprehensive cancer center in Toronto, Canada. Participants completed the Stanford Acute Stress Reaction Questionnaire, Memorial Symptom Assessment Scale, CARES Medical Interaction Subscale, and other psychosocial measures. A multivariate regression analysis was used to assess independent predictors of post-traumatic stress symptoms. RESULTS: Of the 205 participants, 58% were male, mean age was 50.1 +/- 15.4 years, 86% were recently diagnosed, and 94% were receiving active treatment. The mean Stanford Acute Stress Reaction Questionnaire score was 30.2 +/- 22.5, with 27 of 200 (14%) patients meeting criteria for acute stress disorder and 36 (18%) for subsyndromal acute stress disorder. Post traumatic stress symptoms were associated with more physical symptoms, physical symptom distress, attachment anxiety, and perceived difficulty communicating with health-care providers, and poorer spiritual well-being (all p < 0.05). CONCLUSIONS: The present study demonstrates that clinically significant symptoms of traumatic stress are common in acute leukemia and are linked to the degree of physical suffering, to satisfaction with relationships with health-care providers, and with individual psychological characteristics. Longitudinal study is needed to determine the natural history, but these findings suggest that intervention may be indicated to alleviate or prevent traumatic stress in this population. PMID- 22081507 TI - Abnormal eating behaviour in people with a specific phobia of vomiting (emetophobia). AB - OBJECTIVE: The aim of this study was to explore the eating behaviour in people with a specific phobia of vomiting (SPOV), and whether those identified as restricting their food had a greater degree of psychopathology and impairment than those who do not restrict their food. METHOD: We recruited 94 participants with SPOV. They were divided into those who reported restricting their food (SPOV R) (n = 32) because of fear of vomiting and those who did not restrict their food (SPOV-NR) (n = 62). RESULTS: People with SPOV frequently have abnormal eating behaviours to reduce the perceived risk of vomiting. Only 3.7% had a body mass index (BMI) of less than 17.5, and 8.5% had a BMI of less than 18.5. The SPOV-R group had significantly higher frequency of psychopathology and abnormal eating behaviours than the SPOV-NR group. DISCUSSION: Abnormal eating behaviour, BMI, and the degree of food restriction are important factors in the assessment of SPOV. PMID- 22081508 TI - Signal amplification by magnetic force on polydiacetylene supramolecules for detection of prostate cancer. AB - A method in which a permanent magnet is introduced onto polydiacetylene (PDA) vesicle chips is introduced for enhancement of the fluorescence of PDA vesicles. This strategy can be applied to general antibody-based PDA vesicle chips to detect clinically important biomarkers for disease diagnosis. PMID- 22081510 TI - Familial adenomatous polyposis, suspected HNPCC, and Crohn's disease: two cases. PMID- 22081509 TI - Matriptase protects against experimental colitis and promotes intestinal barrier recovery. AB - BACKGROUND: Matriptase is a membrane-anchored serine protease encoded by suppression of tumorigenicity-14 (ST14) that is required for epithelial barrier homeostasis. However, its functional role in inflammatory bowel disease (IBD) is unexplored. METHODS: Matriptase expression in control, Crohn's disease, and ulcerative colitis tissue specimens was studied by quantitative polymerase chain reaction (qPCR) and immunostaining. Matriptase function was investigated by subjecting St14 hypomorphic and control littermates to dextran sodium sulfate (DSS)-induced colitis and by siRNA silencing in cultured monolayers. Mice were analyzed for clinical, histological, molecular, and cellular effects. RESULTS: Matriptase protein and ST14 mRNA levels are significantly downregulated in inflamed colonic tissues from Crohn's disease and ulcerative colitis patients. Matriptase-deficient St14 hypomorphic mice administered DSS for 7 days followed by water without DSS for 3 days develop a severe colitis, with only 30% of the St14 hypomorphic mice surviving to day 14, compared with 100% of control littermates. Persistent colitis in surviving St14 hypomorphic mice was associated with sustained cytokine production, an inability to recover barrier integrity, and enhanced claudin-2 expression. Cytokines implicated in barrier disruption during IBD suppress matriptase expression in T84 epithelial monolayers and restoration of matriptase improves barrier integrity in the cytokine-perturbed monolayers. CONCLUSIONS: These data demonstrate a critical role for matriptase in restoring barrier function to injured intestinal mucosa during colitis, which is suppressed by excessive activation of the immune system. Strategies to enhance matriptase-mediated barrier recovery could be important for intervening in the cycle of inflammation associated with IBD. PMID- 22081511 TI - Estimating the prevalence of dementia: cognitive screening in Glasgow nursing homes. AB - OBJECTIVES: The purpose of this study is to establish existing levels of dementia in nursing homes. DESIGN: The design was a randomised sample of every sixth nursing home resident in Glasgow City. Cognitive testing of 341 residents was carried out using the Standardised Mini Mental State Examination (SMMSE). For clients who had difficulty participating, the Functional Assessment Staging Tool (FAST) was used. Existing dementia diagnoses were compared with the prevalence indicated through cognitive testing. MAIN OUTCOME MEASURES: Standardised Mini Mental State Examination and the FAST were used. SETTING: This study was conducted in the nursing homes in the Glasgow City Council Local Authority, Scotland, UK (N = 49). Forty-eight homes participated in the study and one declined. PARTICIPANTS: The participants were residents of the nursing homes in Glasgow City, including those in existing dementia units (sample = 422 of population 2532); 19 declined and 403 participated. RESULTS: Two hundred thirty four (58%) residents already had a diagnosis of dementia written in their care plans. One hundred twenty-eight residents (31.8%) without diagnosis of dementia in their care plans scored within the range of possible dementia (less than 24/30 on the SMMSE). A group of 55 (13.6%) residents had no diagnosis of dementia but had some type of cognitive impairment recorded in their notes and scored within the range of possible dementia on the SMMSE. CONCLUSION: Existing levels of dementia diagnosis are 58%. This study finds an additional 31.8% of residents without a diagnosis of dementia who score within the range of possible dementia, giving a ceiling of 89.8%. It appears that underdiagnosis of dementia exists within this 31.8% group. PMID- 22081512 TI - Determination of pelvic orientation from sparse ultrasound data for THA operated in the lateral position. AB - BACKGROUND: B-mode ultrasound imaging has the potential to replace conventional percutaneous digitization of bony landmarks in navigated total hip arthroplasties (THAs). For THAs operated in the lateral position, only one side of the pelvis is freely accessible. This paper presents a new ultrasound to statistical shape model (SSM) registration method for operating the pelvis in the lateral position, based on sparse ultrasound images, which does not interfere with the clinical routine in terms of redraping and repositioning the patient. METHODS: It is proposed to use the mid-sagittal plane of the pelvis to symmetrically reflect data derived from sparse B-mode ultrasound images of the ipsilateral patient side to the contralateral side. A SSM of the pelvis is registered to the bilaterally available data without additional information on the pubic tubercle region. RESULTS: The feasibility and robustness of the proposed method were evaluated by comprehensive in silico studies and laboratory experiments with plastic and dry cadaveric pelvises, showing a mean error of 3.48 +/- 1.10 degrees for anteversion angle and 1.26 +/- 1.62 degrees for inclination angle. CONCLUSION: Experimental results demonstrate that the symmetry property of the pelvis could be used for registration in the lateral position without accessing the error prone pubic tubercle landmarks. PMID- 22081513 TI - Angiogenic and antiangiogenic factors before and after resolution of maternal mirror syndrome. AB - Mirror syndrome is a rare condition that involves fetal hydrops, placentomegaly and severe maternal edema. The pathogenesis of this syndrome mimics endothelial dysfunction observed in pre-eclampsia. We report a case of maternal mirror syndrome caused by bilateral fetal hydrothorax that resolved after intrauterine pleuroamniotic shunt placement. At the time of the clinical manifestation there was an antiangiogenic state similar to that seen in pre-eclampsia, which resolved after fetal treatment. Our findings suggest that mirror syndrome is a manifestation of a broad spectrum of pathological conditions that induces an antiangiogenic state. PMID- 22081514 TI - Aurelia aurita-Cnidarian with a prominent medusiod stage. AB - Aurelia aurita has a complex life cycle that consists of several stages including alternating generations of medusa and polyps, huge sexual, and tiny asexual stages. Cnidarian is thought to possess two tissue layers: endoderm (gastroderm) and ectoderm, which are separated by mesoglea in medusa. The determination of the composition of the A. aurita jellyfish mesoglea was performed. New protein "mesoglein" was determined as one of the main components of mesoglea. Mesoglein is synthesized by mesogleal cells (Mc), which are populated A. aurita mesoglea as a high molecular mass precursor. Mc are involved in the formation of noncollagenous "elastic" fibers. Deduced amino acid sequence of mesoglein contains Zona Pellucida (ZP) domain and Delta/Serrate/Lag-2 domain. According to reverse transcription PCR, mesoglein is expressed in the mature medusa exclusively in the Mc. The sperm binding to the ZP is particularly important for successful fertilization. Antibodies against mesoglein stain the plate in the place of contact of germinal epithelium and oocyte. The structure found was named the "contact plate." The contact plate could be the precursor of the ZP. All our data suggest that Mc and, probably, the whole mesoglea originate from the epidermis (ectoderm). Computer search for mesoglein relatives reveals Nematostella and Trichoplax proteins as predicted ORFs, indicating that ZP proteins are quite ancient purchase in the evolution. PMID- 22081515 TI - NHLBI asthma guidelines: no benefit for patients? PMID- 22081516 TI - Mapping of homozygous deletions in verified esophageal adenocarcinoma cell lines and xenografts. AB - Human esophageal adenocarcinoma (EAC) cell lines and xenografts are powerful tools in the search for genetic alterations because these models are composed of pure human cancer cell populations without admixture of normal human cells. In particular detection of homozygous deletions (HDs) is easier using these pure populations of cancer cells. Identification of HDs could potentially lead to the subsequent identification of new tumor suppressor genes (TSGs) involved in esophageal adenocarcinogenesis. Genome wide single nucleotide polymorphism (SNP) arrays were used to identify HDs in 10 verified EAC cell lines and nine EAC xenografts. In total, 61 HDs (range 1-6 per sample) were detected and confirmed by polymerase chain reaction. Besides HDs observed in common fragile genomic regions (n = 26), and gene deserts (n = 8), 27 HDs were located in gene containing regions. HDs were noted for known TSGs, including CDKN2A, SMAD4 and CDH3/CDH1. Twenty-two new chromosomal regions were detected harboring potentially new TSGs involved in EAC carcinogenesis. Two of these regions of homozygous loss, encompassing the ITGAV and RUNX1 gene, were detected in multiple samples indicating a potential role in the carcinogenesis of EAC. To exclude culturing artifacts, these last two deletions were confirmed by fluorescent in situ hybridization in the primary tumors of which the involved cell lines and xenografts were derived. In summary, in this report we describe the identification of HDs in a series of verified EAC cell lines and xenografts. The deletions documented here are a step forward identifying the key genes involved in EAC development. PMID- 22081517 TI - Elevated sweat chloride concentration in children without cystic fibrosis who are receiving topiramate therapy. AB - BACKGROUND: Topiramate, which is used as an anticonvulsant and for migraine prophylaxis in children, causes oligohydrosis as a side-effect, but its effect on sweat chloride concentrations has not been studied systematically. METHODS: Twenty-one children receiving topiramate and 20 healthy controls with no signs or symptoms of pulmonary or gastrointestinal disease and a negative family history for cystic fibrosis (CF) underwent bilateral pilocarpine iontophoresis and sweat collection via Macroduct(r) system. RESULTS: Adequate samples (>15 ul volume) were obtained from 17/19 topiramate subjects (89%), and 19/20 (95%) controls. The mean sweat chloride concentration was 37.7 +/- 18.8 mmol/L for patients receiving topiramate, and 15.9 +/- 6.9 mmol/L for controls (p = 0.0001). The mean sweat volume was 29.1 +/- 17.4 ul for patients receiving topiramate, and 41.2 +/- 17.5 ul for controls (p = 0.037). Overall 8/17 (47%) of patients on topiramate with a measurable sweat chloride had either an intermediate (>40 mmol/L but <60 mmol/L) or elevated (>60 mmol/L) sweat chloride test result, while 0/19 control subjects had elevated sweat chloride (p = 0.0008). Further analysis of the in vitro activity of topiramate on cultured human bronchial epithelial cells in modified Ussing chambers showed no differences in chloride conductance measured in cells exposed to 10 or 50 ug/ml of topiramate when compared to non-exposed cells. CONCLUSIONS: This is the first report of a medication affecting sweat chloride values and shows that topiramate therapy can cause elevated sweat chloride concentrations in the absence of clinical manifestations of CF. PMID- 22081520 TI - Representing and comparing protein folds and fold families using three dimensional shape-density representations. AB - The question of how best to compare and classify the (three-dimensional) structures of proteins is one of the most important unsolved problems in computational biology. To help tackle this problem, we have developed a novel shape-density superposition algorithm called 3D-Blast which represents and superposes the shapes of protein backbone folds using the spherical polar Fourier correlation technique originally developed by us for protein docking. The utility of this approach is compared with several well-known protein structure alignment algorithms using receiver-operator-characteristic plots of queries against the "gold standard" CATH database. Despite being completely independent of protein sequences and using no information about the internal geometry of proteins, our results from searching the CATH database show that 3D-Blast is highly competitive compared to current state-of-the-art protein structure alignment algorithms. A novel and potentially very useful feature of our approach is that it allows an average or "consensus" fold to be calculated easily for a given group of protein structures. We find that using consensus shapes to represent entire fold families also gives very good database query performance. We propose that using the notion of consensus fold shapes could provide a powerful new way to index existing protein structure databases, and that it offers an objective way to cluster and classify all of the currently known folds in the protein universe. PMID- 22081519 TI - Considerations in high-resolution skeletal muscle diffusion tensor imaging using single-shot echo planar imaging with stimulated-echo preparation and sensitivity encoding. AB - Previous studies have shown that skeletal muscle diffusion tensor imaging (DTI) can noninvasively probe changes in the muscle fiber architecture and microstructure in diseased and damaged muscles. However, DTI fiber reconstruction in small muscles and in muscle regions close to aponeuroses and tendons remains challenging because of partial volume effects. Increasing the spatial resolution of skeletal muscle single-shot diffusion-weighted echo planar imaging (DW-EPI) can be hindered by the inherently low signal-to-noise ratio (SNR) of muscle DW EPI because of the short muscle T(2) and the high sensitivity of single-shot EPI to off-resonance effects and T(2)* blurring. In this article, eddy current compensated diffusion-weighted stimulated-echo preparation is combined with sensitivity encoding (SENSE) to maintain good SNR properties and to reduce the sensitivity to distortions and T(2)* blurring in high-resolution skeletal muscle single-shot DW-EPI. An analytical framework is developed to optimize the reduction factor and diffusion weighting time to achieve maximum SNR. Arguments for the selection of the experimental parameters are then presented considering the compromise between SNR, B(0)-induced distortions, T(2)* blurring effects and tissue incoherent motion effects. On the basis of the selected parameters in a high-resolution skeletal muscle single-shot DW-EPI protocol, imaging protocols at lower acquisition matrix sizes are defined with matched bandwidth in the phase encoding direction and SNR. In vivo results show that high-resolution skeletal muscle DTI with minimized sensitivity to geometric distortions and T(2)* blurring is feasible using the proposed methodology. In particular, a significant benefit is demonstrated from a reduction in partial volume effects for resolving multi pennate muscles and muscles with small cross-sections in calf muscle DTI. PMID- 22081518 TI - Channelled scaffolds for engineering myocardium with mechanical stimulation. AB - The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) of the heart are important characteristics in the engineering of functional myocardial tissue. This study reports on the development of chitosan-collagen scaffolds with micropores and an array of parallel channels (~ 200 um in diameter) that were specifically designed for cardiac tissue engineering using mechanical stimulation. The scaffolds were designed to have similar structural and mechanical properties of those of native heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1-2 mm thick) consisted of metabolically active cells that began to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stress promoted cell alignment, elongation, and expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs. PMID- 22081521 TI - Intra- and interoperator reliability of manual and semi-automated measurements of intracranial translucency. AB - OBJECTIVES: To assess the reproducibility of fetal intracranial translucency (IT) measurements performed manually or with SonoNT((r)), a semi-automated caliper placement technique recently introduced for nuchal translucency thickness (NT) measurement. METHODS: This was a retrospective study using 116 stored images of the head (mid-sagittal plane) from normal fetuses in dorsoposterior position at 11-13 weeks. Two experienced operators each measured the IT separately, twice manually and twice using the semi-automated software. Intraoperator and interoperator repeatability were assessed. The mean of the two manual measurements of the more experienced Operator 2 was considered as the 'gold standard'. RESULTS: Seven cases were excluded as the IT could not be recognized by the semi-automated software. In the remaining 109 cases, the interquartile range of the mean IT measurement was 1.9-2.4 mm for Operator 1 and 1.8-2.3 mm for Operator 2 for both the manual and the semi-automated IT measurements. The intraoperator SD for manual measurements was 0.091 mm for Operator 1 and 0.088 mm for Operator 2, and for semi-automated measurements it was 0.054 mm for Operator 1 and 0.067 mm for Operator 2. Concerning interoperator bias of the manual measurements, the mean difference between Operator 1 and Operator 2 was - 0.09 (95% CI, - 0.11 to - 0.07) mm. With respect to the gold standard, the mean bias of the semi-automated measurements was 0.01 (95% CI - 0.01 to 0.03) mm for Operator 1 and - 0.09 (95% CI - 0.11 to - 0.07) mm for Operator 2, indicating good agreement. CONCLUSIONS: Manual IT measurements are reproducible. In addition, IT can be assessed reliably using the semi-automated NT algorithm, leading to standardization of the IT assessment process. PMID- 22081522 TI - One-year investigator-blind randomized multicenter trial comparing Asacol 2.4 g once daily with 800 mg three times daily for maintenance of remission in ulcerative colitis. AB - BACKGROUND: Mesalazine (Asacol) is still widely prescribed in divided doses for ulcerative colitis (UC), despite evidence that adherence is improved by once daily (OD) prescribing. We aimed to investigate whether OD Asacol was as effective as three times (TDS) daily dosing, and to evaluate the role of treatment adherence. METHODS: An investigator-blind randomized trial was undertaken comparing OD Asacol (three 800 mg tablets) versus one 800 mg TDS in maintenance of remission of UC over 1 year. The primary endpoint was relapse rate, and noninferiority would be concluded if the lower limit of the two-sided 95% confidence interval (CI) of the difference in proportions relapsing (TDS-OD) exceeded -10%. Adherence was measured by tablet counts and self-reported adherence. A subgroup of patients used a bottle cap that recorded all bottle opening events. RESULTS: In all, 213 patients were randomized. In the intention to-treat (ITT) population, relapse rates were 31% (95% CI 22%-40%) in the OD and 45% (95% CI 35%-54%) in the TDS group. Primary analysis confirmed the noninferiority of OD dosing. Two of the study populations, ITT and per-protocol (PP), showed potential superiority of OD dosing. All measures of adherence showed that it was significantly better in the OD group. Multivariate analysis, however, showed OD dosing was associated with lower relapse risk independently of adherence. CONCLUSIONS: OD dosing with Asacol 2.4 g is as safe and effective as TDS dosing, and secondary analysis confirmed significantly reduced relapse rates. The benefit, however, was clinically borderline and may relate in part to ease of adherence. PMID- 22081523 TI - Glandular neoplasia and borderline endocervical reporting rates before and after conversion to the SurePath(TM) liquid-based cytology (LBC) system. AB - Reporting rates for glandular neoplasia in 464,754 cervical samples reported at six laboratories in 12-month periods before and after the implementation of SurepathTM LBC processing are compared. The introduction of LBC processing is seen to have resulted in a significant (P = 0.001) increase in the detection rate for endocervical glandular neoplasia (from 2.2 per 10,000 tests to 3.9 per 10,000) while maintaining high levels of reporting specificity. An observed fall in the number of samples reported as showing borderline glandular neoplasia falls short of statistical significance, and the reporting of possible endometrial and 'other' glandular abnormalities appears to be unaffected. The underlying reasons for the observed improvement in detection of endocervical glandular neoplasia are discussed. PMID- 22081525 TI - Divide and rule: cytodiagnosis of thyroid lesions using pattern analysis: a study of 233 cases. AB - Fine needle aspiration cytology (FNAC) of the thyroid is a simple, accurate, fast, economical and safe method for the diagnosis of thyroid lesions on FNA. The objective of this study was application of pattern analysis in the interpretation of thyroid lesions. Two hundred and thirty three cases of thyroid lesion were reviewed, which had histopathological correlation. Smears were classified based on primary (predominant) and secondary (next dominant) pattern and categorized. The variation between combined and final cytological diagnosis was correlated with the histopathological diagnosis. The sensitivity, specificity and diagnostic accuracy for the diagnosis of malignancy were 90.47, 100 and 99.14%. Our study demonstrates the feasibility and applicability of pattern analysis in diagnosing thyroid lesions, which could be easily reproducible. PMID- 22081524 TI - Cutaneous and subcutaneous metastases from internal malignancies: an analysis of cases diagnosed by fine needle aspiration. AB - Cutaneous and subcutaneous metastases from internal malignancies are rare and indicate a dismal outcome for the patient. This study is designed to analyze cases of cutaneous and subcutaneous metastases from a known or unknown primary and evaluate usefulness of fine needle aspiration cytology as a diagnostic modality. The present study is a retrospective analysis of 83 patients who were diagnosed with metastatic skin deposits on fine needle aspiration cytology. Seventy-four patients were previously diagnosed cases of malignancy and nine patients had metastatic deposits simultaneously with the primary tumor. The commonest malignancies showing cutaneous metastases were from breast, colon and rectum, lung, ovary, and thyroid. The differential diagnoses are from primary cutaneous tumors. FNAC provides a rapid diagnosis and should be used as a preferred first line diagnostic modality in such patients. In our study, FNAC yielded a sensitivity and specificity of 100% as a microscopic method for confirmation. PMID- 22081526 TI - Escherichia coli on pleural effusion smear. PMID- 22081527 TI - Calcinosis cutis: diagnosis by fine needle aspiration cytology--a rare case report. AB - Calcinosis cutis is characterized by deposition of calcium salts in the subcutaneous tissues in the body. In this study, we described a case of calcinosis cutis that was diagnosed by fine needle aspiration (FNA) in a 15-year old male. The patient presented with multiple nodules over right forearm and right knee. FNA smears showed flakes of amorphous material indicating calcium along with few macrophages. The presence of amorphous calcium salts along with histiocytes in the appropriate clinical settings is diagnostic of calcinosis cutis. PMID- 22081528 TI - Cytologic findings in two cases of dermoid cysts with malignant transformation. AB - While dermoid cysts are fairly commonly seen in the surgical pathology practice, rarely is the malignant transformation of dermoid cysts seen. Even rarer still is the cytopathologic report of this manifestation. In both of these case reports, the diagnosis of the malignant transformation of a dermoid cyst was made only after the initial cytologic diagnosis of malignancy had been reported and further investigation identified the source of the malignant cells. Unfortunately in both of these cases, the disease was detected at an advanced stage. To my knowledge and with a thorough literature search, the first case will be the first reported case of an adenocarcinoma in a dermoid cyst present in a Pap smear as the initial diagnosis. While the second case of malignant melanoma in a dermoid has been reported in ascitic fluid, such reports are rare. PMID- 22081529 TI - Fine-needle aspiration cytology of primitive neuroectodermal tumor of the urinary bladder: a case report. AB - Primitive neuroectodermal tumors (PNETs) are malignant small round cell tumors, which exhibit a variable degree of neural differentiation. These tumors are usually found in the extraosseous soft tissue and rarely in bones. Occasional cases of PNETs of the urinary bladder have been reported on histopathology. However, to the best of our knowledge, none have been diagnosed on fine-needle aspiration cytology (FNAC). A patient presented to the out-patient department with complaints of a slowly progressive lump in the lower abdomen, which was diagnosed as PNET on FNAC. The smears showed a dispersed population and sheets of malignant small round cells with focal rosette formation and perivascular arrangement of tumor cells. Periodic acid-Schiff staining showed strong cytoplasmic positivity. Immunocytochemistry of the cytology smears also showed strong membrane positivity for CD99 (MIC-2), which was also confirmed on histopathological examination. PNET of the urinary bladder is a distinct entity, which can be diagnosed on FNAC and confirmed by immunohistochemistry. A diagnosis of PNET should be considered as a differential diagnosis in urinary bladder masses, especially in adolescents and young adults. PMID- 22081530 TI - Fine-needle aspiration cytology with histological correlation of chordoma metastatic to the lung: a diagnostic dilemma. AB - Chordoma is an uncommon tumor initially believed to be benign due to the rarity of its metastasis. Cytological, morphological, and immunohistochemical features of chordoma, relating to its origin from notochordal remnants, allows for its accurate diagnosis. A 75-year-old man with a known history of tuberculosis (TB) presented with shortness of breath and a dry cough. A chest X-ray demonstrated a diffuse, infiltrative miliary pattern in both lungs. Bronchial washings submitted for culture and cytological examination did not identify any tuberculous bacilli. Fine needle aspiration cytology (FNAC) showed focal areas of myxoid regions with small, round, uniform mononuclear cells. There was a documented past history of chordoma arising from the L2 vertebrae. Because of the rarity of this lesion in the lung and the limited diagnostic material available with a clinical history of TB and lumbar chordoma, the pathological report rendered on the FNAC was "atypical cells suspicious for metastatic chordoma." A wedge biopsy of the lung confirmed the presence of metastatic pulmonary chordoma. Despite palliative treatment, he died within a year. Although the metastatic potential of chordomas has been recognized and documented, to the best of our knowledge, metastasis of chordoma to the lung diagnosed by FNAC with cytohistological correlation has not been previously reported in the English literature. PMID- 22081531 TI - Decoy cells and malignant cells coexisting in the urine from a transplant recipient with BK virus nephropathy and bladder adenocarcinoma. AB - The search for decoy cells (DC) in urine is widely used as screening for BK virus (BKV) reactivation in transplant recipients. BKV cytopathic effect of DC must not be confused with high-grade urothelial carcinoma. This report presents a case of coexistence of DC and malignant cells in the urine from a transplant recipient with BKV-associated nephropathy (BKVN) and bladder adenocarcinoma. A 38-year-old female with type 1 diabetes mellitus and end-stage renal disease underwent a simultaneous pancreas and kidney transplant. Four years post-transplantation, BK virus studies were performed for renal dysfunction. Isolated DC and DC in casts were identified in urine. Also, the tests for BKV DNA were positive in serum and renal allograft biopsy. BKVN was treatment-resistant and the patient returned to hemodialysis. A kidney transplant nephrectomy was performed 2 years later. The next urine cytology showed, in addition to DC, other distinct cells with nuclear atypia highly suggestive of malignancy. Some cells showed both, malignant and DC features. A bladder adenocarcinoma was diagnosed on biopsy and BKV proteins were demonstrated on tumor cells, supporting a possible role for BKV in the oncogenic pathway in this clinical setting. The presence of DC in the urine from a transplant recipient is the hallmark of BKV activation, but it does not exclude the existence of carcinoma. Furthermore, the presence of highly atypical cells should raise, not eliminate, the possibility of neoplastic transformation of the bladder. PMID- 22081532 TI - A uncommon cause of haemoptysis: metastatic collecting duct renal carcinoma. PMID- 22081533 TI - Apoptotic ciliated cells on sputum smear. PMID- 22081534 TI - How frequently are contraindicated or warned against combinations of drugs prescribed to patients receiving long-term opioid therapy for chronic pain? AB - PURPOSE: To analyse the proportion of patients treated with an opioid for chronic pain who were prescribed concomitant medications that are warned against or contraindicated in the German summary of product characteristics to determine if warnings on drug-drug interactions (DDIs) are observed. METHODS: This retrospective analysis used longitudinal aggregated patient data from the Intercontinental Marketing Services Disease Analyzer in Germany. Patients with two or more prescriptions of morphine, hydromorphone, oxycodone or tramadol from 1 January 2006 to 31 December 2008 were included; drugs prescribed within 30 days of an opioid prescription were identified as concomitant medications. The frequency of concomitant treatment with drugs warned against or contraindicated in the German opioid summary of product characteristics was determined. Concomitant treatment with drugs metabolised by CYP3A4 inhibitors and inducers and CYP2D6 inhibitors was also considered. RESULTS: The Intercontinental Marketing Services database contained 13,405 eligible patients; 72% had concomitant diseases which may increase the risk for DDIs (hypertension, diabetes mellitus, renal failure, renal glomerular disease or renal tubulointerstitial disease). Very few patients received concomitant prescriptions of an opioid with a contraindicated drug. Many patients were prescribed opioids concomitantly with drugs with potential for harmful safety-related DDIs or DDIs that alter the effectiveness of one or more of the opioids. A large proportion of all concomitant prescriptions with potential for DDIs were given to at-risk patients aged 65 years and older. CONCLUSIONS: Many patients that received an opioid for chronic pain were prescribed concomitant medications with the potential for safety-related DDIs or interactions that would alter the effectiveness of the opioid. PMID- 22081537 TI - Pulmonary diffusing capacity in healthy Caucasian children. AB - Previous studies of pulmonary diffusing capacity in children differed greatly in methodologies; numbers of subjects evaluated, and were performed prior to the latest ATS/ERS guidelines. The purpose of our study was to establish reference ranges for the diffusing capacity to carbon monoxide (DL(CO) ) and alveolar volume (V(A) ) in healthy Caucasian children using current international guidelines and contemporary equipment. Healthy children from the United States (N = 303) and from Australia (N = 176) performed acceptable measurements of single breath pulmonary diffusing capacity and alveolar volume according to current ATS/ERS guidelines. The natural log of DL(CO) and V(A) were associated with height, age and an age-sex interaction term, while DL(CO) /V(A) was related to height and the age-sex interaction term only. Adjustment of DL(CO) for hemoglobin (n = 303; USA data only) resulted is a small but significant decrease in DL(CO) of ~1% but did not significantly alter the regression equations. In this dataset there was no influence of center for DL(CO) or DL(CO) /V(A) , while Australian children had a statistically smaller V(A) (mean difference 0.14 L after accounting for height, age and age-sex; P = 0.012). We report that diffusing capacity outcomes can be collated from multiple centers using similar equipment and collection protocols. Using collated data we have derived regression equations for pulmonary diffusing capacity outcomes in healthy Caucasian children aged 5-19 years. PMID- 22081538 TI - Three-dimensional culture of mouse bone marrow cells on stroma formed within a porous scaffold: influence of scaffold shape and cryopreservation of the stromal layer on expansion of haematopoietic progenitor cells. AB - This study's primary goal was to develop an effective ex vivo expansion method for haematopoietic cells. 3D culture of mouse bone marrow cells was performed in porous scaffolds using a sheet or cube shape. Bone marrow cells were cultured on bone marrow-derived stromal layers formed within the scaffolds and the effect of scaffold shape on the expansion of haematopoietic cells was examined. In some experiments, stromal layers within cubic scaffolds were frozen and then used to culture bone marrow cells after thawing. Results show that after comparison, total cell density and expansion of haematopoietic cells were greater in cultures using the cubic scaffold, suggesting that it was superior to the sheet-like scaffold for expanding haematopoietic cells. When cryopreserved stroma was used, it effectively supported the expansion of haematopoietic cells, and a greater expansion of haematopoietic cells [(erythroid and haematopoietic progenitor cells (HPCs)] was achieved than in cultures with stromal cells that had not been cryopreserved. Expansion of cells using cryopreserved stroma had several other advantages such as a shorter culture period than the conventional method, a stable supply of stromal cells, and ease of handling and scaling up. As a result, this is an attractive method for ex vivo expansion of haematopoietic stem cells (HSCs) and HPCs for clinical use. PMID- 22081540 TI - Does pharmacological castration as adjuvant therapy for prostate cancer after radiotherapy affect anxiety and depression levels, cognitive functions and quality of life? AB - INTRODUCTION: Adjuvant hormonotherapy for prostate cancer patients after radical radiotherapy has a well-established value. However, the impact of such treatment on the patients' quality of life remains to be elucidated. OBJECTIVE: The objective is to assess the impact of adjuvant hormonotherapy with luteinizing hormone-releasing hormone analogue after radical radiotherapy on anxiety and depression levels, cognitive function, sexual function and quality of life of prostate cancer patients. MATERIAL AND METHODS: Two groups of patients were tested: men treated with adjuvant hormonotherapy (88 patients) and men without hormonotherapy (61 patients). Anxiety, depression and cognitive functions were evaluated. Patients answered questions addressing problems linked to hormonal equilibrium. The patients rated their mental status, physical status, quality of life and quality of their relationship. RESULTS: There were no statistically significant differences between patients on hormonotherapy and without hormonotherapy in the level of anxiety and depression (p = 0.844 and p = 0.954) as well as in cognitive function (p = 0.661). Satisfactory sexual performance was preserved in 9/65 patients (14%) on hormonotherapy and the same was applied to 19/49 patients (39%) without hormonotherapy. The difference was statistically significant (p = 0.003). Hormonotherapy was associated with decreased libido (p = 0.031), hot flushes (p < 0.001) and sweating (p < 0.001). No statistically significant differences were found between the groups in the self-rated physical and psychological well-being (p = 0.476 and p = 0.597), quality of life (p = 0.622) and quality of relationship (p = 0.064). CONCLUSIONS: Adjuvant hormonotherapy enhances neither anxiety nor depression, does not impair cognitive function but has a negative effect on the patients' sexual function. It does not worsen self-rated quality of relationship and quality of life. PMID- 22081541 TI - Liver nodules in Crohn's ileitis. PMID- 22081542 TI - High-sensitivity C-reactive protein for identification of disease phenotype, active disease, and clinical relapses in Crohn's disease: a marker for patient classification? AB - BACKGROUND: C-reactive protein (CRP) is a traditional nonspecific marker of inflammation, with Crohn's disease (CD) being associated with a strong CRP response. Thus far, no clear cutoff values have been determined. The authors' aim was to investigate whether high-sensitivity (hs)-CRP is useful for the identification disease phenotype, active disease, and relapse during follow-up, using a classification based on the hs-CRP value at diagnosis. METHODS: In all, 260 well-characterized, unrelated, consecutive CD patients (male/female: 120/140; duration: 7.0 +/- 6.1 years), with a complete clinical follow-up, were included. Hs-CRP, clinical activity according to the Harvey-Bradshaw Index, and clinical data (disease phenotype according to the Montreal Classification, extraintestinal manifestations, smoking habits, medical therapy, and surgical events) were prospectively collected between January 1, 2008 and June 1, 2010. Medical records prior to the prospective follow-up period were analyzed retrospectively. RESULTS: In all, 32.3% of CD patients had normal hs-CRP at diagnosis. Elevated hs-CRP at diagnosis was associated with disease location (P = 0.002), noninflammatory disease behavior (P = 0.058), and a subsequent need for later azathioprine/biological therapy (P < 0.001 and P = 0.024), respectively. The accuracy of hs-CRP for identifying patients with active disease during prospective follow-up was good (area under the curve [AUC]: 0.82, cutoff: 10.7 mg/L). AUC was better in patients with an elevated hs-CRP at diagnosis (AUC: 0.92, cutoff: 10.3 mg/L). In Kaplan-Meier and Cox-regression analyses, hs-CRP was an independent predictor of 3- (P = 0.007) or 12-month (P = 0.001) clinical relapses for patients in remission who had elevated hs-CRP at diagnosis. In addition, perianal involvement (P = 0.01) was associated with the 12-month relapse frequency. CONCLUSIONS: Our data suggest that hs-CRP positivity at diagnosis is associated with disease location and behavior, and in patients who are hs-CRP positive at diagnosis, is an accurate marker of disease activity and a predictor of short- and medium-term clinical flare-ups during follow-up. PMID- 22081543 TI - Sustaining the development and implementation of student-centered teaching nationally: the importance of a community of practice. AB - Although the idea of using a workshop to educate potential users about a set of materials or techniques is not new, the workshops described here go beyond simple dissemination and create ongoing communities of practice that support widespread and sustained improvement in the biochemistry classroom. The degree to which pedagogical innovations improve student learning on a national level depends on how broadly they are disseminated and how they are implemented and sustained. Workshops can be effective in disseminating ideas and techniques, but they often fail to sustain implementation. This paper describes Core Collaborators Workshops (CCWs) that were specifically designed for biochemistry faculty to improve the quality of active learning materials, support faculty in transforming their classrooms, and disseminate these efforts nationally. This CCW model proved very effective to date as shown by the fact that, 8 months after the last CCW, all workshop participants reported using at least some of the instructional materials discussed during the workshop. In addition, participants remarked that the superior community building and direct mentoring available through the CCWs greatly increased their confidence in implementing this new curricular approach and has made them more likely to act as leaders themselves. PMID- 22081544 TI - Building student proficiency with scientific literature using the Zotero reference manager platform. AB - While mastery of the scientific literature is a strongly desirable trait for undergraduate students, the sheer volume of the current literature has complicated the challenge of teaching scientific literacy. Part of the response to this ever-increasing volume of resources includes formal instruction in the use of reference manager software while engaging students with the primary literature. This article describes the incorporation of the reference manager program Zotero into a chemical literature course to facilitate the use of digital resources and to better enable them to use proper citation skills in their technical writing. PMID- 22081545 TI - Non-native English language speakers benefit most from the use of lecture capture in medical school. AB - Medical education in the United States and Canada continues to evolve. However, many of the changes in pedagogy are being made without appropriate evaluation. Here, we attempt to evaluate the effectiveness of lecture capture technology as a learning tool in Podiatric medical education. In this pilot project, student performance in an inaugural lecture capture-supported biochemistry course was compared to that in the previous academic year. To examine the impact of online lecture podcasts on student performance a within-subjects design was implemented, a two way ANCOVA with repeated measures. The use of lecture capture-supported pedagogy resulted in significantly higher student test scores, than achieved historically using traditional pedagogy. The overall course performance using this lecture capture-supported pedagogy was almost 6% higher than in the previous year. Non-native English language speakers benefitted more significantly from the lecture capture-supported pedagogy than native English language speakers, since their performance improved by 10.0 points. Given that underrepresented minority (URM) students, whose native language is not English, makes up a growing proportion of medical school matriculates, these observations support the use of lecture capture technology in other courses. Furthermore, this technology may also be used as part of an academic enrichment plan to improve performance on the American Podiatric Medical Licensing Examination, reduce the attrition of URM students and potentially address the predicted minority physician shortage in 2020. PMID- 22081546 TI - Enhanced podcasts for teaching biochemistry to veterinary students. AB - The teaching of biochemistry within medical disciplines presents certain challenges; firstly to relay a large body of complex facts and abstract concepts, and secondly to motivate students that this relatively difficult topic is worth their time to study. Here, nutrient biochemistry was taught within a multidisciplinary module as part of an undergraduate veterinary curriculum. The teaching approach was initially focussed on a mixture of didactic lectures and student-centred activities such as directed group/self learning. In subsequent years the core didactic lectures were replaced with enhanced podcasts covering the same material, along with the introduction of student presentations delivered within groups with both peer and facilitator assessment. These changes were accompanied by an increase in the time dedicated to this topic to allow sufficient time for students to work through podcasts and prepare presentations. The combination of these changes resulted in significant improvements in student performance within an in-course biochemistry long essay. These changes in the teaching approach, and particularly the introduction of extensive podcasts, was well received by students who perceived the process of going through the podcasts as time consuming but allowing them flexibility in both the pace that they studied this topic as well as the location and times that they studied it. PMID- 22081548 TI - pGLO mutagenesis: a laboratory procedure in molecular biology for biology students. AB - A five-session laboratory project was designed to familiarize or increase the laboratory proficiency of biology students and others with techniques and instruments commonly used in molecular biology research laboratories and industries. In this project, the EZ-Tn5 transposon is used to generate and screen a large number of cells transformed with mutagenized pGLO plasmid. EZ-Tn5 carries the kanamycin resistance (Kan(R)) gene, and the pGLO plasmid carries the beta lactamase gene for ampicillin resistance (Amp(R)), the gene encoding green fluorescent protein (GFP) and the arabinose operon repressor (araC). Insertion of the Tn5 transposon into pGLO occurs randomly, and any gene into which it inserts is knocked out. By screening cells transformed with mutagenized pGLO with kanamycin, ampicillin, arabinose and/or for GFP expression in different combinations, pGLO plasmids with mutations in different genes are identified. The locations of these insertions are then mapped approximately by restriction fragment analysis and precisely by sequence analysis of the pGLO plasmid. PMID- 22081547 TI - An exercise in molecular epidemiology: human rhinovirus prevalence and genetics. AB - Human rhinovirus (HRV) is one of the most common human respiratory pathogens and is responsible for the majority of upper respiratory illnesses. Recently, a phylogeny was constructed from all known American Type Culture Collection (ATCC) HRV sequences. From this study, three HRV classifications (HRVA, HRVB, and HRVC) were determined and techniques for classifying new isolates of HRV were reported. The genetic change of this virus in specific populations over time is of great interest to understand the evolution and epidemiology of viruses. To facilitate the collections of HRV sequences over a number of years, a virology experiment was designed in which students test nasal lavage samples to look for HRV infection. Students will learn a variety of techniques including RNA isolation, cDNA synthesis, qPCR, and agarose gel electrophoresis as well as bioinformatic skills though examination of sequences from the HRV-field isolates. Furthermore, students can look at symptom data from subjects to investigate correlations between symptom severity and factors such as stress and sleep patterns. Such information can be used to examine hypotheses regarding HRV mutation, symptom severity and epidemiology. PMID- 22081549 TI - Self-directed student research through analysis of microarray datasets: a computer-based functional genomics practical class for masters-level students. AB - This report describes a linked series of Masters-level computer practical workshops. They comprise an advanced functional genomics investigation, based upon analysis of a microarray dataset probing yeast DNA damage responses. The workshops require the students to analyse highly complex transcriptomics datasets, and were designed to stimulate active learning through experience of current research methods in bioinformatics and functional genomics. They seek to closely mimic a realistic research environment, and require the students first to propose research hypotheses, then test those hypotheses using specific sections of the microarray dataset. The complexity of the microarray data provides students with the freedom to propose their own unique hypotheses, tested using appropriate sections of the microarray data. This research latitude was highly regarded by students and is a strength of this practical. In addition, the focus on DNA damage by radiation and mutagenic chemicals allows them to place their results in a human medical context, and successfully sparks broad interest in the subject material. In evaluation, 79% of students scored the practical workshops on a five-point scale as 4 or 5 (totally effective) for student learning. More broadly, the general use of microarray data as a "student research playground" is also discussed. PMID- 22081550 TI - A linked series of laboratory exercises in molecular biology utilizing bioinformatics and GFP. AB - Molecular biologists commonly use bioinformatics to map and analyze DNA and protein sequences and to align different DNA and protein sequences for comparison. Additionally, biologists can create and view 3D models of protein structures to further understand intramolecular interactions. The primary goal of this 10-week laboratory was to introduce the importance of bioinformatics in molecular biology. Students employed multiprimer, site-directed mutagenesis to create variant colors from a plasmid expressing green fluorescent protein (GFP). Isolated mutant plasmid from Escherichia coli showing changes in fluorescence were sequenced. Students used sequence alignment tools, protein translator tools, protein modeling, and visualization to analyze the potential effect of their mutations within the protein structure. This laboratory linked molecular techniques and bioinformatics to promote and expand the understanding of experimental results in an upper-level undergraduate laboratory course. PMID- 22081551 TI - Commentary: analysis of examination questions expose low faculty expectations. PMID- 22081552 TI - Problem-solving test: submitochondrial localization of proteins. AB - Terms to be familiar with before you start to solve the test: mitochondria, outer membrane, inner membrane, intermembrane space, mitochondrial matrix, mitochondrial fraction, cell fractionation by differential centrifugation, pellet, supernatant, detergents, phenol, cytosolic fraction, integral and peripheral membrane proteins, hypotonic solution, SDS-polyacrylamide gel electrophoresis, Western blotting. PMID- 22081553 TI - Commentary: left hand, right hand and on the other hand. PMID- 22081554 TI - Proteopedia entry: triose phosphate isomerase. PMID- 22081556 TI - Factors accounting for a missed diagnosis of cystic fibrosis after newborn screening. AB - Newborn screening is a public health policy program involving the centralized testing laboratory, infant and their family, primary care provider, and subspecialist for confirmatory testing and follow-up of abnormal results. Cystic fibrosis (CF) newborn screening has now been enacted in all 50 states and the District of Columbia and throughout many countries in the world. Although CF neonatal screening will identify the vast majority of infants with CF, there are many factors in the newborn screening system that can lead to a missed diagnosis of CF. To inform clinicians, this article summarizes the CF newborn screening system and highlights 14 factors that can account for a missed diagnosis of CF. Care providers should maintain a high suspicion for CF if there are compatible symptoms, regardless of the results of the newborn screening test. These factors in newborn screening programs leading to a missed diagnosis of CF present opportunities for quality improvement in specimen collection, laboratory analysis of immunoreactive tryspinogen (IRT) and CF mutation testing, communication, and sweat testing. PMID- 22081557 TI - Comparing the effects of insulin glargine and thiazolidinediones on plasma lipids in type 2 diabetes: a patient-level pooled analysis. AB - BACKGROUND: The prevalence of dyslipidaemia and the risk of cardiovascular disease are elevated in patients with type 2 diabetes. This analysis compared the effects of insulin glargine versus thiazolidinediones (TZDs) on lipid profiles. METHODS: Patient-level data were pooled from two randomized clinical studies. The population included 552 men and women aged >18 years, diagnosed with type 2 diabetes for at least 6 months, on metformin and/or sulphonylurea, and with A(1C) >=7.5% and <12.0% at screening. Lipid outcome measures included change from baseline in lipid levels [low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, triglycerides, and free fatty acids] and attainment of lipid goals for LDL-C, non-HDL-C, and triglycerides. RESULTS: Both insulin glargine and TZDs improved lipid profiles from baseline values. Compared with TZDs, treatment with insulin glargine led to 7.9% greater reduction in LDL-C (p < 0.0003), 7.5% greater reduction in non-HDL-C (p < 0.0001), and 7.8% greater reduction in total cholesterol (p < 0.0001), whereas the HDL-C increase with TZD was 7.6% greater than that with insulin glargine (p < 0.0001). The percentage of patients attaining the lipid goals was comparable between insulin glargine and pioglitazone, but lower for rosiglitazone. Insulin glargine improved glycaemic control more than TZDs; however, insulin glargine caused more hypoglycaemia. Treatment with TZDs caused more weight gain and peripheral oedema. CONCLUSION: These findings suggest that the favourable effects of insulin glargine on plasma lipid profiles should be considered among the advantages of treatment with insulin glargine as they are for TZDs. PMID- 22081558 TI - Radial mechanical properties of single-walled boron nitride nanotubes. AB - The radial mechanical properties of single-walled boron nitride nanotubes (SW BNNTs) are investigated by atomic force microscopy. Nanomechanical measurements reveal the radial deformation of individual SW-BNNTs in both elastic and plastic regimes. The measured effective radial elastic moduli of SW-BNNTs are found to follow a decreasing trend with an increase in tube diameter, ranging from 40.78 to 1.85 GPa for tube diameters of 0.58 to 2.38 nm. The results show that SW-BNNTs have relatively lower effective radial elastic moduli than single-walled carbon nanotubes (SWCNTs). The axially strong, but radially supple characteristics suggest that SW-BNNTs may be superior to SWCNTs as reinforcing additives for nanocomposite applications. PMID- 22081559 TI - Lung function distinguishes preschool children with CF from healthy controls in a multi-center setting. AB - RATIONALE: Conducting clinical trials in cystic fibrosis (CF) preschoolers has been limited by lack of sensitive lung function measures performed across sites. OBJECTIVES: (1) Assess feasibility and short-term reproducibility of spirometry, forced oscillometry (FO), and inductance plethysmography (IP) in a multi-center preschool population; (2) compare ability of each technique to differentiate lung function of CF preschoolers and controls; (3) evaluate longitudinal changes in lung function; (4) estimate sample sizes for future trials. METHODS: A longitudinal, multi-center study of CF preschoolers was conducted utilizing standardized equipment, rigorous site training, and centralized lung function data review. CF subjects participated in up to four study visits 6 months apart, plus a 2-week reproducibility visit. Controls had one study visit. RESULTS: Ninety-three CF subjects and 87 controls participated. Acceptability rates were lowest for spirometry (55%) and highest for IP (77%). Spirometry success increased with age and having a prior acceptable measurement. FEV(1) , FEV(0.5) , and FEF(25-75) were lower for CF subjects than for controls; spirometric z-scores declined with age. IP measures of thoracoabdominal asynchrony were greater for CF subjects than for controls. FO indices did not distinguish CF from controls. FEV(1) and FEV(0.5) are able to detect the smallest treatment effect for a given sample size. CONCLUSIONS: Spirometry appears more sensitive than IP or FO for detecting lung disease in CF preschoolers; spirometric indices decline with age. Future trials using spirometry should include a run-in period for training and require acceptable data prior to enrollment. However, near-normal spirometric measurements in CF preschoolers may lead to difficulty detecting a treatment effect. PMID- 22081560 TI - PGA-associated heterotopic chondrocyte cocultures: implications of nasoseptal and auricular chondrocytes in articular cartilage repair. AB - The availability of autologous articular chondrocytes remains a limiting issue in matrix assisted autologous chondrocyte transplantation. Non-articular heterotopic chondrocytes could be an alternative autologous cell source. The aims of this study were to establish heterotopic chondrocyte cocultures to analyze cell-cell compatibilities and to characterize the chondrogenic potential of nasoseptal chondrocytes compared to articular chondrocytes. Primary porcine and human nasoseptal and articular chondrocytes were investigated for extracellular cartilage matrix (ECM) expression in a monolayer culture. 3D polyglycolic acid- (PGA) associated porcine heterotopic mono- and cocultures were assessed for cell vitality, types II, I, and total collagen-, and proteoglycan content. The type II collagen, lubricin, and Sox9 gene expressions were significantly higher in articular compared with nasoseptal monolayer chondrocytes, while type IX collagen expression was lower in articular chondrocytes. Only beta1-integrin gene expression was significantly inferior in humans but not in porcine nasoseptal compared with articular chondrocytes, indicating species-dependent differences. Heterotopic chondrocytes in PGA cultures revealed high vitality with proteoglycan rich hyaline-like ECM production. Similar amounts of type II collagen deposition and type II/I collagen ratios were found in heterotopic chondrocytes cultured on PGA compared to articular chondrocytes. Quantitative analyses revealed a time dependent increase in total collagen and proteoglycan content, whereby the differences between heterotopic and articular chondrocyte cultures were not significant. Nasoseptal and auricular chondrocytes monocultured in PGA or cocultured with articular chondrocytes revealed a comparable high chondrogenic potential in a tissue engineering setting, which created the opportunity to test them in vivo for articular cartilage repair. PMID- 22081561 TI - Bacterial whole-cell biosensor for glutamine with applications for quantifying and visualizing glutamine in plants. AB - A whole-cell biosensor for glutamine (GlnLux) was constructed by transforming an Escherichia coli glutamine (Gln) auxotroph with a constitutive lux reporter gene. Measurements of Gln in plant extracts using GlnLux correlated with quantification using high-performance liquid chromatography (Spearman's r = 0.95). GlnLux permitted charge-coupled-device (CCD) imaging of Gln from whole plant organs. PMID- 22081563 TI - Daphnia magna, a host for evaluation of bacterial virulence. AB - We show that Daphnia magna can be used to assess acute virulence of pathogens relevant to human health, such as Pseudomonas aeruginosa or Photorhabdus asymbiotica. Analysis of bacterial mutants suggests that P. aeruginosa uses similar mechanisms to infect Daphnia and other hosts. PMID- 22081562 TI - Distinct transcriptional profiles and phenotypes exhibited by Escherichia coli O157:H7 isolates related to the 2006 spinach-associated outbreak. AB - In 2006, a large outbreak of Escherichia coli O157:H7 was linked to the consumption of ready-to-eat bagged baby spinach in the United States. The likely sources of preharvest spinach contamination were soil and water that became contaminated via cattle or feral pigs in the proximity of the spinach fields. In this study, we compared the transcriptional profiles of 12 E. coli O157:H7 isolates that possess the same two-enzyme pulsed-field gel electrophoresis (PFGE) profile and are related temporally or geographically to the above outbreak. These E. coli O157:H7 isolates included three clinical isolates, five isolates from separate bags of spinach, and single isolates from pasture soil, river water, cow feces, and a feral pig. The three clinical isolates and two spinach bag isolates grown in cultures to stationary phase showed decreased expression of many sigma(S)-regulated genes, including gadA, osmE, osmY, and katE, compared with the soil, water, cow, feral pig, and the other three spinach bag isolates. The decreased expression of these sigma(S)-regulated genes was correlated with the decreased resistance of the isolates to acid stress, osmotic stress, and oxidative stress but increases in scavenging ability. We also observed that intraisolate variability was much more pronounced among the clinical and spinach isolates than among the environmental isolates. Together, the transcriptional and phenotypic differences of the spinach outbreak isolates of E. coli O157:H7 support the hypothesis that some variants within the spinach bag retained characteristics of the preharvest isolates, whereas other variants with altered gene expression and phenotypes infected the human host. PMID- 22081564 TI - Metagenomic analysis of stress genes in microbial mat communities from Antarctica and the High Arctic. AB - Polar and alpine microbial communities experience a variety of environmental stresses, including perennial cold and freezing; however, knowledge of genomic responses to such conditions is still rudimentary. We analyzed the metagenomes of cyanobacterial mats from Arctic and Antarctic ice shelves, using high-throughput pyrosequencing to test the hypotheses that consortia from these extreme polar habitats were similar in terms of major phyla and subphyla and consequently in their potential responses to environmental stresses. Statistical comparisons of the protein-coding genes showed similarities between the mats from the two poles, with the majority of genes derived from Proteobacteria and Cyanobacteria; however, the relative proportions differed, with cyanobacterial genes more prevalent in the Antarctic mat metagenome. Other differences included a higher representation of Actinobacteria and Alphaproteobacteria in the Arctic metagenomes, which may reflect the greater access to diasporas from both adjacent ice-free lands and the open ocean. Genes coding for functional responses to environmental stress (exopolysaccharides, cold shock proteins, and membrane modifications) were found in all of the metagenomes. However, in keeping with the greater exposure of the Arctic to long-range pollutants, sequences assigned to copper homeostasis genes were statistically (30%) more abundant in the Arctic samples. In contrast, more reads matching the sigma B genes were identified in the Antarctic mat, likely reflecting the more severe osmotic stress during freeze up of the Antarctic ponds. This study underscores the presence of diverse mechanisms of adaptation to cold and other stresses in polar mats, consistent with the proportional representation of major bacterial groups. PMID- 22081565 TI - Characterization and functional analyses of R-specific enoyl coenzyme A hydratases in polyhydroxyalkanoate-producing Ralstonia eutropha. AB - A genome survey of polyhydroxyalkanoate (PHA)-producing Ralstonia eutropha H16 detected the presence of 16 orthologs of R-specific enoyl coenzyme A (enoyl-CoA) hydratase, among which three proteins shared high homologies with the enzyme specific to enoyl-CoAs of medium chain length encoded by phaJ4 from Pseudomonas aeruginosa (phaJ4(Pa)). The recombinant forms of the three proteins, termed PhaJ4a(Re) to PhaJ4c(Re), actually showed enoyl-CoA hydratase activity with R specificity, and the catalytic efficiencies were elevated as the substrate chain length increased from C(4) to C(8). PhaJ4a(Re) and PhaJ4b(Re) showed >10-fold higher catalytic efficiency than PhaJ4c(Re). The functions of the new PhaJ4 proteins were investigated using previously engineered R. eutropha strains as host strains; these strains are capable of synthesizing poly((R)-3 hydroxybutyrate-co-(R)-3-hydroxyhexanoate) [P(3HB-co-3HHx)] from soybean oil. Deletion of phaJ4a(Re) from the chromosome resulted in significant decrease of 3HHx composition in the accumulated copolyester, whereas no change was observed with deletion of phaJ4b(Re) or phaJ4c(Re), indicating that only PhaJ4a(Re) was one of the major enzymes supplying the (R)-3HHx-CoA monomer through beta oxidation. Introduction of phaJ4a(Re) or phaJ4b(Re) into the R. eutropha strains using a broad-host-range vector enhanced the 3HHx composition of the copolyesters, but the introduction of phaJ4c(Re) did not. The two genes were then inserted into the pha operon on chromosome 1 of the engineered R. eutropha by homologous recombination. These modifications enabled the biosynthesis of P(3HB co-3HHx) composed of a larger 3HHx fraction without a negative impact on cell growth and PHA production on soybean oil, especially when phaJ4a(Re) or phaJ4b(Re) was tandemly introduced with phaJ(Ac) from Aeromonas caviae. PMID- 22081566 TI - Differential protection of Cry1Fa toxin against Spodoptera frugiperda larval gut proteases by cadherin orthologs correlates with increased synergism. AB - The Cry proteins produced by Bacillus thuringiensis (Bt) are the most widely used biopesticides effective against a range of crop pests and disease vectors. Like chemical pesticides, development of resistance is the primary threat to the long term efficacy of Bt toxins. Recently discovered cadherin-based Bt Cry synergists showed the potential to augment resistance management by improving efficacy of Cry toxins. However, the mode of action of Bt Cry synergists is thus far unclear. Here we elucidate the mechanism of cadherin-based Cry toxin synergism utilizing two cadherin peptides, Spodoptera frugiperda Cad (SfCad) and Manduca sexta Cad (MsCad), which differentially enhance Cry1Fa toxicity to Spodoptera frugiperda neonates. We show that differential SfCad- and MsCad-mediated protection of Cry1Fa toxin in the Spodoptera frugiperda midgut correlates with differential Cry1Fa toxicity enhancement. Both peptides exhibited high affinity for Cry1Fa toxin and an increased rate of Cry1Fa-induced pore formation in S. frugiperda. However, only SfCad bound the S. frugiperda brush border membrane vesicle and more effectively prolonged the stability of Cry1Fa toxin in the gut, explaining higher Cry1Fa enhancement by this peptide. This study shows that cadherin fragments may enhance B. thuringiensis toxicity by at least two different mechanisms or a combination thereof: (i) protection of Cry toxin from protease degradation in the insect midgut and (ii) enhancement of pore-forming ability of Cry toxin. PMID- 22081567 TI - Methicillin-resistant coagulase-negative staphylococci on pig farms as a reservoir of heterogeneous staphylococcal cassette chromosome mec elements. AB - Methicillin-resistant Staphylococcus aureus (MRSA) likely originated by acquisition of the staphylococcal cassette chromosome mec (SCCmec) from coagulase negative staphylococci (CNS). However, it is unknown whether the same SCCmec types are present in MRSA and CNS that reside in the same niche. Here we describe a study to determine the presence of a potential mecA reservoir among CNS recovered from 10 pig farms. The 44 strains belonged to 10 different Staphylococcus species. All S. aureus strains belonged to sequence type 398 (ST398), with SCCmec types V and IVa. Type IVc, as well as types III and VI, novel subtypes of type IV, and not-typeable types, were found in CNS. S. aureus, S. epidermidis, and S. haemolyticus shared SCCmec type V. The presence of SCCmec type IVc in several staphylococcal species isolated from one pig farm is noteworthy, suggesting exchange of this SCCmec type in CNS, but the general distribution of this SCCmec type still has to be established. In conclusion, this study shows that SCCmec types among staphylococcal species on pig farms are heterogeneous. On two farms, more than one recovered staphylococcal species harbored the same SCCmec type. We conclude that staphylococci on pig farms act as a reservoir of heterogeneous SCCmec elements. These staphylococci may act as a source for transfer of SCCmec to S. aureus. PMID- 22081568 TI - Colonization kinetics of different methicillin-resistant Staphylococcus aureus sequence types in pigs and host susceptibilities. AB - In this study we investigated the kinetics of colonization, the host susceptibility and transmissibility of methicillin-resistant Staphylococcus aureus (MRSA) after nasal treatment of pigs with three different MRSA strains of distinctive clonal lineages (sequence type 398 [ST398], ST8, and ST9), and origin in weaning piglets. The colonization dose of 5.0 * 10(8) CFU/animal was determined in preliminary animal studies. A total of 57 piglets were randomly divided into four test groups and one control group. Each of three test groups was inoculated intranasally with either MRSA ST8, MRSA ST9, or MRSA ST398. The fourth group was a mixture of animals inoculated with MRSA ST398 and noninoculated "sentinel" animals. Clinical signs, the nasal, conjunctival, and skin colonization of MRSA, fecal excretion, and organ distribution of MRSA, as well as different environmental samples were examined. After nasal inoculation with MRSA piglets of all four test groups showed no clinical signs of an MRSA infection. MRSA was present on the nasal mucosa, skin, and conjunctiva in all four test groups, including sentinel animals. Likewise, fecal excretion and internal colonization of MRSA ST8, ST9, and ST398 could be shown in each group. However, fecal excretion and the colonization rate of the nasal mucosa with MRSA ST9 were significantly lower in the first days after infection than in test groups infected with ST8 and ST398. The results of this study suggest differences in colonization potential of the different MRSA types in pigs. Furthermore, colonization of lymph nodes (e.g., the ileocecal lymph node) with MRSA of the clonal lineage ST398 was demonstrated. PMID- 22081569 TI - Diurnal variation in Enterococcus species composition in polluted ocean water and a potential role for the enterococcal carotenoid in protection against photoinactivation. AB - Enterococcus species composition was determined each hour for 72 h at a polluted marine beach in Avalon, Santa Catalina Island, CA. Species composition during the day was significantly different from that at night, based on an analysis of similarity. Enterococcus faecium and E. faecalis were more prevalent at night than during the day, while E. hirae and other Enterococcus species were more prevalent during the day than the night. Enterococcus spp. containing a yellow pigment were more common during the day than the night, suggesting that the pigmented phenotype may offer a competitive advantage under sunlit conditions. A laboratory microcosm experiment established that the pigmented E. casseliflavus isolate and a pigmented E. faecalis isolate recovered from the field site decay slower than a nonpigmented E. faecalis isolate in a solar simulator in simulated, clear seawater. This further supports the idea that the yellow carotenoid pigment in Enterococcus provides protection under sunlit conditions. The findings are in accordance with previous work with other carotenoid-containing nonphotosynthetic and photosynthetic bacteria that suggests that the carotenoid is able to quench reactive oxygen species capable of causing photoinactivation and photostress. The results suggest that using enterococcal species composition as a microbial source tracking tool may be hindered by the differential environmental persistence of pigmented and nonpigmented enterococci. PMID- 22081570 TI - Factors driving potential ammonia oxidation in Canadian arctic ecosystems: does spatial scale matter? AB - Ammonia oxidation is a major process in nitrogen cycling, and it plays a key role in nitrogen limited soil ecosystems such as those in the arctic. Although mm scale spatial dependency of ammonia oxidizers has been investigated, little is known about the field-scale spatial dependency of aerobic ammonia oxidation processes and ammonia-oxidizing archaeal and bacterial communities, particularly in arctic soils. The purpose of this study was to explore the drivers of ammonia oxidation at the field scale in cryosols (soils with permafrost within 1 m of the surface). We measured aerobic ammonia oxidation potential (both autotrophic and heterotrophic) and functional gene abundance (bacterial amoA and archaeal amoA) in 279 soil samples collected from three arctic ecosystems. The variability associated with quantifying genes was substantially less than the spatial variability observed in these soils, suggesting that molecular methods can be used reliably evaluate spatial dependency in arctic ecosystems. Ammonia-oxidizing archaeal and bacterial communities and aerobic ammonia oxidation were spatially autocorrelated. Gene abundances were spatially structured within 4 m, whereas biochemical processes were structured within 40 m. Ammonia oxidation was driven at small scales (<1m) by moisture and total organic carbon, whereas gene abundance and other edaphic factors drove ammonia oxidation at medium (1 to 10 m) and large (10 to 100 m) scales. In these arctic soils heterotrophs contributed between 29 and 47% of total ammonia oxidation potential. The spatial scale for aerobic ammonia oxidation genes differed from potential ammonia oxidation, suggesting that in arctic ecosystems edaphic, rather than genetic, factors are an important control on ammonia oxidation. PMID- 22081571 TI - Abundance and composition of epiphytic bacterial and archaeal ammonia oxidizers of marine red and brown macroalgae. AB - Ammonia-oxidizing bacteria (AOB) and archaea (AOA) are important for nitrogen cycling in marine ecosystems. Little is known about the diversity and abundance of these organisms on the surface of marine macroalgae, despite the algae's potential importance to create surfaces and local oxygen-rich environments supporting ammonia oxidation at depths with low dissolved oxygen levels. We determined the abundance and composition of the epiphytic bacterial and archaeal ammonia-oxidizing communities on three species of macroalgae, Osmundaria volubilis, Phyllophora crispa, and Laminaria rodriguezii, from the Balearic Islands (western Mediterranean Sea). Quantitative PCR of bacterial and archaeal 16S rRNA and amoA genes was performed. In contrast to what has been shown for most other marine environments, the macroalgae's surfaces were dominated by bacterial amoA genes rather than those from the archaeal counterpart. On the basis of the sequences retrieved from AOB and AOA amoA gene clone libraries from each algal species, the bacterial ammonia-oxidizing communities were related to Nitrosospira spp. and to Nitrosomonas europaea and only 6 out of 15 operational taxonomic units (OTUs) were specific for the host species. Conversely, the AOA diversity was higher (43 OTUs) and algal species specific, with 17 OTUs specific for L. rodriguezii, 3 for O. volubilis, and 9 for P. crispa. Altogether, the results suggest that marine macroalgae may exert an ecological niche for AOB in marine environments, potentially through specific microbe-host interactions. PMID- 22081573 TI - Genetic markers for rapid PCR-based identification of gull, Canada goose, duck, and chicken fecal contamination in water. AB - Avian feces contaminate waterways but contribute fewer human pathogens than human sources. Rapid identification and quantification of avian contamination would therefore be useful to prevent overestimation of human health risk. We used subtractive hybridization of PCR-amplified gull fecal 16S RNA genes to identify avian-specific fecal rRNA gene sequences. The subtracters were rRNA genes amplified from human, dog, cat, cow, and pig feces. Recovered sequences were related to Enterobacteriaceae (47%), Helicobacter (26%), Catellicoccus (11%), Fusobacterium (11%), and Campylobacter (5%). Three PCR assays, designated GFB, GFC, and GFD, were based on recovered sequence fragments. Quantitative PCR assays for GFC and GFD were developed using SYBR green. GFC detected down to 0.1 mg gull feces/100 ml (corresponding to 2 gull enterococci most probable number [MPN]/100 ml). GFD detected down to 0.1 mg chicken feces/100 ml (corresponding to 13 Escherichia coli MPN/100 ml). GFB and GFC were 97% and 94% specific to gulls, respectively. GFC cross-reacted with 35% of sheep samples but occurred at about 100,000 times lower concentrations in sheep. GFD was 100% avian specific and occurred in gulls, geese, chickens, and ducks. In the United States, Canada, and New Zealand, the three markers differed in their geographic distributions but were found across the range tested. These assays detected four important bird groups contributing to fecal contamination of waterways: gulls, geese, ducks, and chickens. Marker distributions across North America and in New Zealand suggest that they will have broad applicability in other parts of the world as well. PMID- 22081574 TI - Development of a simvastatin selection marker for a hyperthermophilic acidophile, Sulfolobus islandicus. AB - We report here a novel selectable marker for the hyperthermophilic crenarchaeon Sulfolobus islandicus. The marker cassette is composed of the sac7d promoter and the hmg gene coding for the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (P(sac7d)-hmg), which confers simvastatin resistance to this crenarchaeon. The basic plasmid vector pSSR was constructed by substituting the pyrEF gene of the expression vector pSeSD for P(sac7d)-hmg with which the Sulfolobus expression plasmids pSSRlacS, pSSRAherA, and pSSRNherA were constructed. Characterization of Sulfolobus transformants carrying pSSRlacS indicated that the plasmid was properly maintained under selection. High-level expression of the His(6)-tagged HerA helicase was obtained with the cells harboring pSSRAherA. The establishment of two efficient selectable markers (pyrEF and hmg) was subsequently exploited for genetic analysis. A herA merodiploid strain of S. islandicus was constructed using pyrEF marker and used as the host to obtain pSSRNherA transformant with simvastatin selection. While the gene knockout (DeltaherA) cells generated from the herA merodiploid cells failed to form colonies in the presence of 5-fluoroorotic acid (5-FOA), the mutant cells could be rescued by expression of the gene from a plasmid (pSSRNherA), because their transformants formed colonies on a solid medium containing 5-FOA and simvastatin. This demonstrates that HerA is essential for cell viability of S. islandicus. To our knowledge, this is the first application of an antibiotic selectable marker in genetic study for a hyperthermophilic acidophile and in the crenarchaeal lineage. PMID- 22081575 TI - Controlled gene expression in bifidobacteria by use of a bile-responsive element. AB - The promoter activity of the upstream region of the bile-inducible gene betA from Bifidobacterium longum subsp. longum NCC2705 was characterized. DNA fragments were cloned into the reporter vector pMDYAbfB, and the arabinofuranosidase activity was determined under different in vitro conditions. A segment of 469 bp was found to be the smallest operational unit that retains bile inducibility. The reporter activity was strongly affected by the presence of ox gall, cholate, and conjugated cholate, but not by other bile salts and cell-surface-acting compounds. Remarkably, this bile-inducible system was also active in other bifidobacteria containing betA homologs. PMID- 22081576 TI - Efficient biostimulation of native and introduced quorum-quenching Rhodococcus erythropolis populations is revealed by a combination of analytical chemistry, microbiology, and pyrosequencing. AB - Degradation of the quorum-sensing (QS) signals known as N-acylhomoserine lactones (AHL) by soil bacteria may be useful as a beneficial trait for protecting crops, such as potato plants, against the worldwide pathogen Pectobacterium. In this work, analytical chemistry and microbial and molecular approaches were combined to explore and compare biostimulation of native and introduced AHL-degrading Rhodococcus erythropolis populations in the rhizosphere of potato plants cultivated in farm greenhouses under hydroponic conditions. We first identified gamma-heptalactone (GHL) as a novel biostimulating agent that efficiently promotes plant root colonization by AHL-degrading R. erythropolis population. We also characterized an AHL-degrading biocontrol R. erythropolis isolate, R138, which was introduced in the potato rhizosphere. Moreover, root colonization by AHL-degrading bacteria receiving different combinations of GHL and R138 treatments was compared by using a cultivation-based approach (percentage of AHL degrading bacteria), pyrosequencing of PCR-amplified rrs loci (total bacterial community), and quantitative PCR (qPCR) of the qsdA gene, which encodes an AHL lactonase in R. erythropolis. Higher densities of the AHL-degrading R. erythropolis population in the rhizosphere were observed when GHL treatment was associated with biocontrol strain R138. Under this condition, the introduced R. erythropolis population displaced the native R. erythropolis population. Finally, chemical analyses revealed that GHL, gamma-caprolactone (GCL), and their by products, gamma-hydroxyheptanoic acid and gamma-hydroxycaproic acid, rapidly disappeared from the rhizosphere and did not accumulate in plant tissues. This integrative study highlights biostimulation as a potential innovative approach for improving root colonization by beneficial bacteria. PMID- 22081577 TI - Isolation of bacteria capable of growth with 2-methylisoborneol and geosmin as the sole carbon and energy sources. AB - Using a relatively simple enrichment technique, geosmin and 2-methylisoborneol (MIB)-biodegrading bacteria were isolated from a digestion basin in an aquaculture unit. Comparison of 16S rRNA gene sequences affiliated one of the three isolates with the Gram-positive genus Rhodococcus, while the other two isolates were found to be closely related to the Gram-negative family Comamonadaceae (Variovorax and Comamonas). Growth rates and geosmin and MIB removal rates by the isolates were determined under aerated and nonaerated conditions in mineral medium containing either of the two compounds as the sole carbon and energy source. All isolates exhibited their fastest growth under aerobic conditions, with generation times ranging from 3.1 to 5.7 h, compared to generation times of up to 19.1 h in the nonaerated flasks. Incubation of the isolates with additional carbon sources caused a significant increase in their growth rates, while removal rates of geosmin and MIB were significantly lower than those for incubation with only geosmin or MIB. By fluorescence in situ hybridization, members of the genera Rhodococcus and Comamonas were detected in geosmin- and MIB-enriched sludge from the digestion basin. PMID- 22081572 TI - Cow teat skin, a potential source of diverse microbial populations for cheese production. AB - The diversity of the microbial community on cow teat skin was evaluated using a culture-dependent method based on the use of different dairy-specific media, followed by the identification of isolates by 16S rRNA gene sequencing. This was combined with a direct molecular approach by cloning and 16S rRNA gene sequencing. This study highlighted the large diversity of the bacterial community that may be found on teat skin, where 79.8% of clones corresponded to various unidentified species as well as 66 identified species, mainly belonging to those commonly found in raw milk (Enterococcus, Pediococcus, Enterobacter, Pantoea, Aerococcus, and Staphylococcus). Several of them, such as nonstarter lactic acid bacteria (NSLAB), Staphylococcus, and Actinobacteria, may contribute to the development of the sensory characteristics of cheese during ripening. Therefore, teat skin could be an interesting source or vector of biodiversity for milk. Variations of microbial counts and diversity between the farms studied have been observed. Moreover, Staphylococcus auricularis, Staphylococcus devriesei, Staphylococcus arlettae, Streptococcus bovis, Streptococcus equinus, Clavibacter michiganensis, Coprococcus catus, or Arthrobacter gandavensis commensal bacteria of teat skin and teat canal, as well as human skin, are not common in milk, suggesting that there is a breakdown of microbial flow from animal to milk. It would then be interesting to thoroughly study this microbial flow from teat to milk. PMID- 22081578 TI - Molecular diversity of the syndinean genus Euduboscquella based on single-cell PCR analysis. AB - The genus Euduboscquella is one of a few described genera within the syndinean dinoflagellates, an enigmatic lineage with abundant diversity in marine environmental clone libraries based on small subunit (SSU) rRNA. The region composed of the SSU through to the partial large subunit (LSU) rRNA was determined from 40 individual tintinnid ciliate loricae infected with Euduboscquella sampled from eight surface water sites in the Northern Hemisphere, producing seven distinct SSU sequences. The corresponding host SSU rRNA region was also amplified from eight host species. The SSU tree of Euduboscquella and syndinean group I sequences from environmental clones had seven well-supported clades and one poorly supported clade across data sets from 57 to 692 total sequences. The genus Euduboscquella consistently formed a supported monophyletic clade within a single subclade of group I sequences. For most parasites with identical SSU sequences, the more variable internal transcribed spacer (ITS) to LSU rRNA regions were polymorphic at 3 to 10 sites. However, in E. cachoni there was variation between ITS to LSU copies at up to 20 sites within an individual, while in a parasite of Tintinnopsis spp., variation between different individuals ranged up to 19 polymorphic sites. However, applying the compensatory base change model to the ITS2 sequences suggested no compensatory changes within or between individuals with the same SSU sequence, while one to four compensatory changes between individuals with similar but not identical SSU sequences were found. Comparisons between host and parasite phylogenies do not suggest a simple pattern of host or parasite specificity. PMID- 22081579 TI - Characterization of Phascolarctobacterium succinatutens sp. nov., an asaccharolytic, succinate-utilizing bacterium isolated from human feces. AB - Isolation, cultivation, and characterization of the intestinal microorganisms are important for understanding the comprehensive physiology of the human gastrointestinal (GI) tract microbiota. Here, we isolated two novel bacterial strains, YIT 12067(T) and YIT 12068, from the feces of healthy human adults. Phylogenetic analysis indicated that they belonged to the same species and were most closely related to Phascolarctobacterium faecium ACM 3679(T), with 91.4% to 91.5% 16S rRNA gene sequence similarities, respectively. Substrate availability tests revealed that the isolates used only succinate; they did not ferment any other short-chain fatty acids or carbohydrates tested. When these strains were cocultured with the xylan-utilizing and succinate-producing bacterium Paraprevotella xylaniphila YIT 11841(T), in medium supplemented with xylan but not succinate, their cell numbers became 2 to 3 orders of magnitude higher than those of the monoculture; succinate became undetectable, and propionate was formed. Database analysis revealed that over 200 uncultured bacterial clones from the feces of humans and other mammals showed high sequence identity (>98.7%) to YIT 12067(T). Real-time PCR analysis also revealed that YIT 12067(T)-like bacteria were present in 21% of human fecal samples, at an average level of 3.34 * 10(8) cells/g feces. These results indicate that YIT 12067(T)-like bacteria are distributed broadly in the GI tract as subdominant members that may adapt to the intestinal environment by specializing to utilize the succinate generated by other bacterial species. The phylogenetic and physiological properties of YIT 12067(T) and YIT 12068 suggest that these strains represent a novel species, which we have designated Phascolarctobacterium succinatutens sp. nov. PMID- 22081580 TI - Acinetobacter insertion sequence ISAba11 belongs to a novel family that encodes transposases with a signature HHEK motif. AB - Experimental and in silico PCR analysis targeting ISAba11 and TnAbaR islands in 196 epidemiologically unrelated Acinetobacter strains representative of >=19 species were performed. The first two Acinetobacter baumannii ISAba11 elements identified had been found to map to the same site on TnAbaR transposons. However, no further evidence of physical linkage between the two elements was demonstrated. Indeed, examination of 25 definite or putative insertion sites suggested limited sequence specificity. Importantly, an aacC1-tagged version of ISAba11 was shown to actively transpose in A. baumannii. Similarity searches identified nine iso-ISAba11 elements in Acinetobacter and one in Enhydrobacter and single representatives of four distant homologs in bacteria belonging to the phyla "Cyanobacteria" and Proteobacteria. Phylogenetic, sequence, and structural analyses of ISAba11 and/or its associated transposase (Tnp(ISAba11)) suggested that these elements be assigned to a new family. All five homologs encode transposases with a shared extended signature comprising 16 invariant residues within the N2, N3, and C1 regions, four of which constituted the cardinal ISAba11 family HHEK motif that is substituted for the YREK DNA binding motif conserved in the IS4 family. Additionally, ISAba11 family members were associated with either no flanking direct repeat (DR) or an ISAba11-typical 5-bp DR and possessed variable-length terminal inverted repeats that exhibited extensive intrafamily sequence identity. Given the limited pairwise identity among Tnp(ISAba11) homologs and the observed restricted distribution of ISAba11, we propose that substantial gaps persist in the evolutionary record of ISAba11 and that this element represents a recent though potentially highly significant entrant into the A. baumannii gene pool. PMID- 22081581 TI - Community composition, toxigenicity, and environmental conditions during a cyanobacterial bloom occurring along 1,100 kilometers of the Murray River. AB - A cyanobacterial bloom impacted over 1,100 km of the Murray River, Australia, and its tributaries in 2009. Physicochemical conditions in the river were optimal to support a bloom at the time. The data suggest that at least three blooms occurred concurrently in different sections of the river, with each having a different community composition and associated cyanotoxin profile. Microscopic and genetic analyses suggested the presence of potentially toxic Anabaena circinalis, Microcystis flos-aquae, and Cylindrospermopsis raciborskii at many locations. Low concentrations of saxitoxins and cylindrospermopsin were detected in Anabaena and Cylindrospermopsis populations. A multiplex quantitative PCR was used, employing novel oligonucleotide primers and fluorescent TaqMan probes, to examine bloom toxigenicity. This single reaction method identified the presence of the major cyanotoxin-producing species present in these environmental samples and also quantified the various toxin biosynthesis genes. A large number of cells present throughout the bloom were not potential toxin producers or were present in numbers below the limit of detection of the assay and therefore not an immediate health risk. Potential toxin-producing cells, possessing the cylindrospermopsin biosynthesis gene (cyrA), predominated early in the bloom, while those possessing the saxitoxin biosynthesis gene (sxtA) were more common toward its decline. In this study, the concentrations of cyanotoxins measured via enzyme-linked immunosorbent assay (ELISA) correlated positively with the respective toxin gene copy numbers, indicating that the molecular method may be used as a proxy for bloom risk assessment. PMID- 22081582 TI - Extrafine aerosols and peripheral airway function in asthma. PMID- 22081583 TI - Estimating the annual number of false negative cystic fibrosis newborn screening tests. PMID- 22081584 TI - Analysis of the associations between lung function and clinical features in preschool children with cystic fibrosis. AB - OBJECTIVE: To analyze cross-sectional and longitudinal associations between lung function measures and clinical features in a cohort of preschool children with cystic fibrosis (CF). METHODS: Longitudinal eight-center observational study of children with CF aged 36-60 months at enrollment, who underwent semiannual pulmonary function tests (PFTs) for up to 2 years consisting of spirometry (all 8 sites), forced oscillometry (FO, 5 sites), and measures of thoracoabdominal asynchrony using respiratory inductive plethysmography (IP, 5 sites). RESULTS: Ninety-three subjects were enrolled; 181 acceptable spirometry measurements from 71 subjects, 128 FO from 47 subjects, and 142 IP from 50 subjects were available for analysis. Cross sectional analyses did not detect an association between any PFT parameter at enrollment and Pseudomonas aeruginosa (Pa) status, CF gene mutation class, Wisconsin cough score, Shwachman score, environmental tobacco smoke exposure, family history of asthma, or nutritional indices. In longitudinal analyses, Pa infection within 6 months preceding enrollment was associated with a significantly greater rate of decline in z-scores for forced expiratory flow between 25 and 75% of forced vital capacity (FEF(25-75) ) (-1.3 vs. -0.4 Z scores/year, P = 0.024) and greater thoracoabdominal asynchrony measured by IP (mean phase angle difference 4.6 degrees , P = 0.004). No other significant longitudinal associations were observed. CONCLUSIONS: Prior Pa infection is associated with a greater rate of decline in FEF(25-75) z-score and mild thoracoabdominal asynchrony in preschool children with CF. In this multicenter US study, significant associations between other lung function measures and clinical features were not detected. PMID- 22081585 TI - Kinetic modelling of DNA replication initiation in budding yeast. AB - DNA replication is restricted to a specific time window of the cell cycle, called S phase. Successful progression through S phase requires replication to be properly regulated to ensure that the entire genome is duplicated exactly once, without errors, in a timely fashion. As a result, DNA replication has evolved into a tightly regulated process involving the coordinated action of numerous factors that function in all phases of the cell cycle. Biochemical mechanisms driving the eukaryotic cell division cycle have been the subject of a number of mathematical models. However, cell cycle networks reported in literature so far have not addressed the steps of DNA replication events. In particular, the assembly of the replication machinery is crucial for the timing of S phase. This event, called "initiation", which occurs in late M / early G1 of the cell cycle, starts with the assembly of the pre-replicative complex (pre-RC) at the origins of replication on the DNA. Its activation depends on the availability of different kinase complexes, cyclin-dependent kinases (CDKs) and Dbf-dependent kinase (DDK), which phosphorylate specific components of the pre-RC to convert it into the pre-initiation complex (pre-IC). We have developed an ODE-based model of the network responsible for this process in budding yeast by using mass-action kinetics. We considered all steps from the assembly of the first components at the DNA replication origin up to the active replisome that recruits the polymerases and verified the computational dynamics with the available literature data. Our results highlighted the link between activation of CDK and DDK and the step-by-step formation of both pre-RC and pre-IC, suggesting S-CDK (Cdk1-Clb5,6) to be the main regulator of the process. PMID- 22081586 TI - Predicting protein complex geometries with linear scoring functions. AB - Protein-Protein interactions play an important role in many cellular processes. However experimental determination of the protein complex structure is quite difficult and time consuming. Hence, there is need for fast and accurate in silico protein docking methods. These methods generally consist of two stages: (i) a sampling algorithm that generates a large number of candidate complex geometries (decoys), and (ii) a scoring function that ranks these decoys such that nearnative decoys are higher ranked than other decoys. We have recently developed a neural network based scoring function that performed better than other state-of-the-art scoring functions on a benchmark of 65 protein complexes. Here, we use similar ideas to develop a method that is based on linear scoring functions. We compare the linear scoring function of the present study with other knowledge-based scoring functions such as ZDOCK 3.0, ZRANK and the previously developed neural network. Despite its simplicity the linear scoring function performs as good as the compared state-of-the-art methods and predictions are simple and rapid to compute. PMID- 22081587 TI - Characterizing common substructures of ligands for GPCR protein subfamilies. AB - The G-protein coupled receptor (GPCR) superfamily is the largest class of proteins with therapeutic value. More than 40% of present prescription drugs are GPCR ligands. The high therapeutic value of GPCR proteins and recent advancements in virtual screening methods gave rise to many virtual screening studies for GPCR ligands. However, in spite of vast amounts of research studying their functions and characteristics, 3D structures of most GPCRs are still unknown. This makes target-based virtual screenings of GPCR ligands extremely difficult, and successful virtual screening techniques rely heavily on ligand information. These virtual screening methods focus on specific features of ligands on GPCR protein level, and common features of ligands on higher levels of GPCR classification are yet to be studied. Here we extracted common substructures of GPCR ligands of GPCR protein subfamilies. We used the SIMCOMP, a graph-based chemical structure comparison program, and hierarchical clustering to reveal common substructures. We applied our method to 850 GPCR ligands and we found 53 common substructures covering 439 ligands. These substructures contribute to deeper understanding of structural features of GPCR ligands which can be used in new drug discovery methods. PMID- 22081589 TI - Comparison of gene expression profiles produced by CAGE, illumina microarray and real time RT-PCR. AB - Several technologies are currently used for gene expression profiling, such as Real Time RT-PCR, microarray and CAGE (Cap Analysis of Gene Expression). CAGE is a recently developed method for constructing transcriptome maps and it has been successfully applied to analyzing gene expressions in diverse biological studies. The principle of CAGE has been developed to address specific issues such as determination of transcriptional starting sites, the study of promoter regions and identification of new transcripts. Here, we present both quantitative and qualitative comparisons among three major gene expression quantification techniques, namely: CAGE, illumina microarray and Real Time RT-PCR, by showing that the quantitative values of each method are not interchangeable, however, each of them has unique characteristics which render all of them essential and complementary. Understanding the advantages and disadvantages of each technology will be useful in selecting the most appropriate technique for a determined purpose. PMID- 22081588 TI - A systems biology approach: modelling of Aquaporin-2 trafficking. AB - In healthy individuals, dehydration of the body leads to release of the hormone vasopressin from the pituitary. Via the bloodstream, vasopressin reaches the collecting duct cells in the kidney, where the water channel Aquaporin-2 (AQP2) is expressed. After stimulation of the vasopressin V2 receptor by vasopressin, intracellular AQP2-containing vesicles fuse with the apical plasma membrane of the collecting duct cells. This leads to increased water reabsorption from the pro-urine into the blood and therefore to enhanced retention of water within the body. Using existing biological data we propose a mathematical model of AQP-2 trafficking and regulation in collecting duct cells. Our model includes the vasopressin receptor, adenylate cyclase, protein kinase A, and intracellular as well as membrane located AQP2. To model the chemical reactions we used ordinary differential equations (ODEs) based on mass action kinetics. We employ known protein concentrations and time series data to estimate the kinetic parameters of our model and demonstrate its validity. Through generating, testing and ranking different versions of the model, we show that some model versions can describe the data well as soon as important regulatory parts such as the reduction of the signal by internalization of the vasopressin-receptor or the negative feedback loop representing phosphodiesterase activity are included. We perform time dependent sensitivity analysis to identify the reactions that have the greatest influence on the cAMP and membrane located AQP2 levels over time. We predict the time courses for membrane located AQP2 at different vasopressin concentrations, compare them with newly generated data and discuss the competencies of the model. PMID- 22081591 TI - Gene regulatory network clustering for graph layout based on microarray gene expression data. AB - We propose a statistical model realizing simultaneous estimation of gene regulatory network and gene module identification from time series gene expression data from microarray experiments. Under the assumption that genes in the same module are densely connected, the proposed method detects gene modules based on the variational Bayesian technique. The model can also incorporate existing biological prior knowledge such as protein subcellular localization. We apply the proposed model to the time series data from a synthetically generated network and verified the effectiveness of the proposed model. The proposed model is also applied the time series microarray data from HeLa cell. Detected gene module information gives the great help on drawing the estimated gene network. PMID- 22081590 TI - On the performance of methods for finding a switching mechanism in gene expression. AB - We address an issue of detecting a switching mechanism in gene expression, where two genes are positively correlated for one experimental condition while they are negatively correlated for another. We compare the performance of existing methods for this issue, roughly divided into two types: interaction test (IT) and the difference of correlation coefficients. Interaction test, currently a standard approach for detecting epistasis in genetics, is the log-likelihood ratio test between two logistic regressions with/without an interaction term, resulting in checking the strength of interaction between two genes. On the other hand, two correlation coefficients can be computed for two experimental conditions and the difference of them shows the alteration of expression trends in a more straightforward manner. In our experiments, we tested three different types of correlation coefficients: Pearson, Spearman and a midcorrelation (biweight midcorrelation). The experiment was performed by using ~ 2.3 * 10(9) combinations selected out of the GEO (Gene Expression Omnibus) database. We sorted all combinations according to the p-values of IT or by the absolute values of the difference of correlation coefficients and then visually evaluated the top ranked combinations in terms of the switching mechanism. The result showed that 1) combinations detected by IT included non-switching combinations and 2) Pearson was affected by outliers easily while Spearman and the midcorrelation seemed likely to avoid them. PMID- 22081592 TI - Fluxviz - Cytoscape plug-in for visualization of flux distributions in networks. AB - MOTIVATION: Methods like FBA and kinetic modeling are widely used to calculate fluxes in metabolic networks. For the analysis and understanding of simulation results and experimentally measured fluxes visualization software within the network context is indispensable. RESULTS: We present Flux Viz, an open-source Cytoscape plug-in for the visualization of flux distributions in molecular interaction networks. FluxViz supports (i) import of networks in a variety of formats (SBML, GML, XGMML, SIF, BioPAX, PSI-MI) (ii) import of flux distributions as CSV, Cytoscape attributes or VAL files (iii) limitation of views to flux carrying reactions (flux subnetwork) or network attributes like localization (iv) export of generated views (SVG, EPS, PDF, BMP, PNG). Though FluxViz was primarily developed as tool for the visualization of fluxes in metabolic networks and the analysis of simulation results from FASIMU, a flexible software for batch flux balance computation in large metabolic networks, it is not limited to biochemical reaction networks and FBA but can be applied to the visualization of arbitrary fluxes in arbitrary graphs. AVAILABILITY: The platform-independent program is an open-source project, freely available at http://sourceforge.net/projects/fluxvizplugin/ under GNU public license, including manual, tutorial and examples. PMID- 22081593 TI - Comprehensive genomic analysis of sulfur-relay pathway genes. AB - Many cofactors and nucleotides containing sulfur atoms are known to have important functions in a variety of organisms. Recently, the biosynthetic pathways of these sulfur containing compounds have been revealed, where many enzymes relay sulfur atoms. Increasing evidence also suggests that the prokaryotic sulfur-relay enzymes might be the evolutionary origin of ubiquitination and the related systems that control a wide range of physiological processes in eukaryotic cells. However, these sulfur-relay enzymes have been studied in only a small number of organisms. Here we carried out comparative genomic analysis and examined the presence and absence of sulfurtransferases utilized in the biosynthetic pathways of molybdenum cofactor (Moco), 2 thiouridine (S(2)U), and 4-thiouridine (S(4)U), and IscS, a cysteine desulfurase. We found that all eukaryotes and many other organisms lack the intermediate enzymes in S(2)U biosynthesis. It is also found that most genes lack rhodanese homology domain (RHD), a catalytic domain of sulfurtransferase. Some organisms have a conserved sequence composed of about 100 residues in the C terminus of TusA, different from RHD. Host-associated organisms have a tendency to lose Moco biosynthetic enzymes, and some organisms have MoaD-MoaE fusion protein. Our findings suggest that sulfur-relay pathways have been so diversified that some putative sulfurtransferases possibly function in other unknown pathways. PMID- 22081595 TI - Genome-wide analysis of plant UGT family based on sequence and substrate information. AB - UGTs (UDP glycosyltransferase) are the largest glycosyltransferase gene family in higher plants, modifying secondary metabolites, hormones, and xenobiotics. This gene family plays an important role in the vast diversity of plant secondary metabolites specific to species. Experimental data of biochemical activities and physiological roles of plant UGTs are increasing but most UGTs are not still functionally characterized. To understand their catalytic specificity and function from sequence data, phylogenetic analyses have been achieved mainly in Arabidopsis, but massive and comprehensive approach covering various species has not been applied yet. In this study, we collected 733 UGT sequences derived from 96 plant species and 252 substrate specificity data. We constructed a phylogenetic tree and divided most part of these genes into nine sequence groups, which are characterized by biochemical specificity. Furthermore, we performed genome-wide analysis of seven plant species UGTs by mapping them into these groups. We propose this is the first step to understand whole glycosylated secondary metabolites of each plant species from its genome information. PMID- 22081594 TI - Phylogenetic analysis of lipid mediator GPCRs. AB - Lipid mediator is the collective term for prostanoids, leukotrienes, lysophospholipids, platelet-activating factor, endocannabinoids and other bioactive lipids, that are involved in various physiological functions including inflammation, immune regulation and cellular development. They act by binding to their ligand-specific G-protein coupled receptors (GPCRs). Since 1990's a number of lipid GPCRs have been cloned in humans, with a few more identified in other vertebrates. However, the conservation of these receptors has been poorly investigated in other eukaryotes. Herein we performed a phylogenetic analysis by collecting their orthologs in 13 eukaryotes with complete genomes. The analysis shows that orthologs for prostanoid receptors are likely to be conserved in the 13 eukaryotes. In contrast, those for lysophospholipid and cannabinoid receptors appear to be conserved only in vertebrates and chordates. Receptors for leukotrienes and other bioactive lipids are limited to vertebrates. These results indicate that the lipid mediators and their receptors have coevolved with the development of highly modulated physiological functions such as immune regulation and the formation of the central nervous system. Accordingly, examining the presence and role of lipid mediator GPCR orthologs in invertebrate species can provide insight into the development of fundamental biological processes across diverse taxa. PMID- 22081597 TI - Analyzing gene coexpression data by an evolutionary model. AB - Coexpressed genes are tentatively translated into proteins that are involved in similar biological functions. Here, we constructed gene coexpression networks from collected microarray data of the organisms Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli. Their degree distributions show the common property of an overrepresentation of highly connected nodes followed by a sudden truncation. In order to analyze this behavior, we present an evolutionary model simulating the genetic evolution. This model assumes that new genes emerge by duplication from a small initial set of primordial genes. Our model does not include the removal of unused genes but selective pressure is indirectly taken into account by preferentially duplicating the old genes. Thus, gene duplication represents the emergence of a new gene and its successful establishment. After a duplication event, all genes are slightly but iteratively mutated, thus altering their expression patterns. Our model is capable of reproducing global properties of the investigated coexpression networks. We show that our model reflects the mean inter-node distances and especially the characteristic humps in the degree distribution that, in the biological examples, result from functionally related genes. PMID- 22081596 TI - Robust gene network analysis reveals alteration of the STAT5a network as a hallmark of prostate cancer. AB - We develop a general method to identify gene networks from pair-wise correlations between genes in a microarray data set and apply it to a public prostate cancer gene expression data from 69 primary prostate tumors. We define the degree of a node as the number of genes significantly associated with the node and identify hub genes as those with the highest degree. The correlation network was pruned using transcription factor binding information in VisANT (http://visant.bu.edu/) as a biological filter. The reliability of hub genes was determined using a strict permutation test. Separate networks for normal prostate samples, and prostate cancer samples from African Americans (AA) and European Americans (EA) were generated and compared. We found that the same hubs control disease progression in AA and EA networks. Combining AA and EA samples, we generated networks for low low (<7) and high (>=7) Gleason grade tumors. A comparison of their major hubs with those of the network for normal samples identified two types of changes associated with disease: (i) Some hub genes increased their degree in the tumor network compared to their degree in the normal network, suggesting that these genes are associated with gain of regulatory control in cancer (e.g. possible turning on of oncogenes). (ii) Some hubs reduced their degree in the tumor network compared to their degree in the normal network, suggesting that these genes are associated with loss of regulatory control in cancer (e.g. possible loss of tumor suppressor genes). A striking result was that for both AA and EA tumor samples, STAT5a, CEBPB and EGR1 are major hubs that gain neighbors compared to the normal prostate network. Conversely, HIF-lalpha is a major hub that loses connections in the prostate cancer network compared to the normal prostate network. We also find that the degree of these hubs changes progressively from normal to low grade to high grade disease, suggesting that these hubs are master regulators of prostate cancer and marks disease progression. STAT5a was identified as a central hub, with ~120 neighbors in the prostate cancer network and only 81 neighbors in the normal prostate network. Of the 120 neighbors of STAT5a, 57 are known cancer related genes, known to be involved in functional pathways associated with tumorigenesis. Our method is general and can easily be extended to identify and study networks associated with any two phenotypes. PMID- 22081598 TI - Collocation-based sparse estimation for constructing dynamic gene networks. AB - One of the open problems in systems biology is to infer dynamic gene networks describing the underlying biological process with mathematical, statistical and computational methods. The first-order difference equation-based models such as dynamic Bayesian networks and vector autoregressive models were used to infer time-lagged relationships between genes from time-series microarray data. However, two primary problems greatly reduce the effectiveness of current approaches. The first problem is the tacit assumption that time lag is stationary. The second is the inseparability between measurement noise and process noise (unmeasured disturbances that pass through time process). To address these problems, we propose a stochastic differential equation model for inferring continuous-time dynamic gene networks under the situation in which both of the process noise and the observation noise exist. We present a collocation based sparse estimation for simultaneous parameter estimation and model selection in the model. The collocation-based approach requires considerably less computational effort than traditional methods in ordinary stochastic differential equation models. We also incorporate various biological knowledge easily to refine the estimation accuracy with the proposed method. The results using simulated data and real time-series expression data of human primary small airway epithelial cells demonstrate that the proposed approach outperforms competing approaches and can provide significant genes influenced by gefitinib. PMID- 22081599 TI - Different groups of metabolic genes cluster around early and late firing origins of replication in budding yeast. AB - DNA replication is a fundamental process that is tightly regulated during the cell cycle. In budding yeast it starts from multiple origins of replication and proceeds in a timely fashion according to a reproducible temporal program until the entire DNA is replicated exactly once per cell cycle. In this program an origin seems to have an inherent firing probability at a specific time in S-phase that is conserved over the population. However, what exactly determines the origin initiation time remains obscure. In this work, we analyze the gene content that clusters around replication origins following the assumption that inherent origin properties that determine staggered initiation times could potentially be mirrored in the close origin proximity. We perform a Gene Ontology term enrichment test and find that metabolic genes are significantly over-represented in the regions that are close to the starting points of DNA replication. Furthermore, functional analysis also reveals that catabolic genes cluster around early firing origins, whereas anabolic genes can rather be found in the proximity of late firing origins of replication. We speculate that, in budding yeast, gene function around replication origins correlates with their intrinsic probability to initiate DNA replication at a given point in S-phase. PMID- 22081600 TI - Integer programming-based method for completing signaling pathways and its application to analysis of colorectal cancer. AB - Signaling pathways are often represented by networks where each node corresponds to a protein and each edge corresponds to a relationship between nodes such as activation, inhibition and binding. However, such signaling pathways in a cell may be affected by genetic and epigenetic alteration. Some edges may be deleted and some edges may be newly added. The current knowledge about known signaling pathways is available on some public databases, but most of the signaling pathways including changes upon the cell state alterations remain largely unknown. In this paper, we develop an integer programming-based method for inferring such changes by using gene expression data. We test our method on its ability to reconstruct the pathway of colorectal cancer in the KEGG database. PMID- 22081601 TI - G1 and G2 arrests in response to osmotic shock are robust properties of the budding yeast cell cycle. AB - Boolean modeling has been successfully applied to the budding yeast cell cycle to demonstrate that both its structure and its timing are robustly designed. However, from these studies few conclusions can be drawn how robust the cell cycle arrest upon osmotic stress and pheromone exposure might be. We therefore implement a compact Boolean model of the S. cerevisiae cell cycle including its interfaces with the High Osmolarity Glycerol (HOG) and the pheromone pathways. We show that all initial states of our model robustly converge to a cyclic attractor in the absence of stress inputs whereas pheromone exposure and osmotic stress lead to convergence to singleton states which correspond to G1 and G2 arrest in silico. A comparison with random Boolean networks reveals, that cell cycle arrest under osmotic stress is a highly robust property of the yeast cell cycle. We implemented our model using the novel frontend booleannetGUI to the python software booleannet. PMID- 22081602 TI - A dynamic programming algorithm to predict synthesis processes of tree-structured compounds with graph grammar. AB - For several decades, many methods have been developed for predicting organic synthesis paths. However these methods have non-polynomial computational time. In this paper, we propose a bottom-up dynamic programming algorithm to predict synthesis paths of target tree-structured compounds. In this approach, we transform the synthesis problem of tree-structured compounds to the generation problem of unordered trees by regarding tree-structured compounds and chemical reactions as unordered trees and rules, respectively. In order to represent rules corresponding to chemical reactions, we employ a subclass of NLC (Node Label Controlled) grammars. We also give some computational results on this algorithm. PMID- 22081603 TI - Studies of binding of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) to fibroblast growth factor inducible 14 (Fn14). AB - To perform highly sensitive cellular binding studies with TNF-like weak inducer of apoptosis (TWEAK), we developed a bioluminescent variant of soluble TWEAK (GpL FLAG-TNC-TWEAK) by fusing it genetically to the C terminus of the luciferase of Gaussia princeps (GpL). Equilibrium binding studies on human (HT1080 and HT29) and murine (Renca and B16) cell lines at 37 degrees C revealed high affinities of human TWEAK from 53 to 112 pm. The dissociation rate constant of the TWEAK Fn14 interaction was between 0.48*10(-3) s(-1) (HT29) and 0.58*10(-3) s(-1) (HT1080) for the human molecules, and the association rate constant obtained was 3.3*10(6) m(-1) s(-1) for both cell lines. It has been shown previously that oligomerization of soluble TWEAK trimers results in enhanced Fn14-mediated activation of the classical NFkappaB pathway. Binding studies with GpL-FLAG-TNC TWEAK trimers oligomerized by help of a FLAG tag-specific antibody gave no evidence for a major increase in Fn14 occupancy by oligomerized ligand despite strongly enhanced induction of the NFkappaB target IL8. Thus, aggregated complexes of soluble TWEAK and Fn14 have a higher intrinsic activity to stimulate the classical NFkappaB pathway and qualitatively differ from isolated trimeric TWEAK-Fn14 complexes. Furthermore, determination of IL8 induction as a function of occupied activated receptors revealed that the intrinsic capability of TNFR1 to stimulate the classical NFkappaB pathway and IL8 production was ~100-fold higher than Fn14. Thus, although ~25 activated TNFR1 trimers were sufficient to trigger half-maximal IL8 production, more than 2500 cell-bound oligomerized TWEAK trimers were required to elicit a similar response. PMID- 22081604 TI - Low resolution structure and dynamics of a colicin-receptor complex determined by neutron scattering. AB - Proteins that translocate across cell membranes need to overcome a significant hydrophobic barrier. This is usually accomplished via specialized protein complexes, which provide a polar transmembrane pore. Exceptions to this include bacterial toxins, which insert into and cross the lipid bilayer itself. We are studying the mechanism by which large antibacterial proteins enter Escherichia coli via specific outer membrane proteins. Here we describe the use of neutron scattering to investigate the interaction of colicin N with its outer membrane receptor protein OmpF. The positions of lipids, colicin N, and OmpF were separately resolved within complex structures by the use of selective deuteration. Neutron reflectivity showed, in real time, that OmpF mediates the insertion of colicin N into lipid monolayers. This data were complemented by Brewster Angle Microscopy images, which showed a lateral association of OmpF in the presence of colicin N. Small angle neutron scattering experiments then defined the three-dimensional structure of the colicin N-OmpF complex. This revealed that colicin N unfolds and binds to the OmpF-lipid interface. The implications of this unfolding step for colicin translocation across membranes are discussed. PMID- 22081605 TI - Galactose differentially modulates lunatic and manic fringe effects on Delta1 induced NOTCH signaling. AB - NOTCH signaling induced by Delta1 (DLL1) and Jagged1 (JAG1) NOTCH ligands is modulated by the beta3N-acetylglucosaminyl transferase Fringe. LFNG (Lunatic Fringe) and MFNG (Manic Fringe) transfer N-acetylglucosamine (GlcNAc) to O-fucose attached to EGF-like repeats of NOTCH receptors. In co-culture NOTCH signaling assays, LFNG generally enhances DLL1-induced, but inhibits JAG1-induced, NOTCH signaling. In mutant Chinese hamster ovary (CHO) cells that do not add galactose (Gal) to the GlcNAc transferred by Fringe, JAG1-induced NOTCH signaling is not inhibited by LFNG or MFNG. In mouse embryos lacking B4galt1, NOTCH signaling is subtly reduced during somitogenesis. Here we show that DLL1-induced NOTCH signaling in CHO cells was enhanced by LFNG, but this did not occur in either Lec8 or Lec20 CHO mutants lacking Gal on O-fucose glycans. Lec20 mutants corrected with a B4galt1 cDNA became responsive to LFNG. By contrast, MFNG promoted DLL1-induced NOTCH signaling better in the absence of Gal than in its presence. This effect was reversed in Lec8 cells corrected by expression of a UDP Gal transporter cDNA. The MFNG effect was abolished by a DDD to DDA mutation that inactivates MFNG GlcNAc transferase activity. The binding of soluble NOTCH ligands and NOTCH1/EGF1-36 generally reflected changes in NOTCH signaling caused by LFNG and MFNG. Therefore, the presence of Gal on O-fucose glycans differentially affects DLL1-induced NOTCH signaling modulated by LFNG versus MFNG. Gal enhances the effect of LFNG but inhibits the effect of MFNG on DLL1 induced NOTCH signaling, with functional consequences for regulating the strength of NOTCH signaling. PMID- 22081606 TI - Serine/threonine phosphatase Stp1 mediates post-transcriptional regulation of hemolysin, autolysis, and virulence of group B Streptococcus. AB - Elucidating how serine/threonine phosphatases regulate kinase function and bacterial virulence is critical for our ability to combat these infections. Group B streptococci (GBS) are beta-hemolytic Gram-positive bacteria that cause invasive infections in humans. To adapt to environmental changes, GBS encodes signaling mechanisms comprising two component systems and eukaryotic-like enzymes. We have previously described the importance of the serine/threonine kinase Stk1 to GBS pathogenesis. However, how the presence or absence of the cognate serine/threonine phosphatase Stp1 affects Stk1 function and GBS virulence is not known. Here, we show that GBS deficient only in Stp1 expression are markedly reduced for their ability to cause systemic infections, exhibit decreased beta-hemolysin/cytolysin activity, and show increased sensitivity to autolysis. Although transcription of genes important for beta-hemolysin/cytolysin expression and export is similar to the wild type (WT), 294 genes (excluding stp1) showed altered expression in the stp1 mutant and included autolysin genes. Furthermore, phosphopeptide enrichment analysis identified that 35 serine/threonine phosphopeptides, corresponding to 27 proteins, were unique to the stp1 mutant. This included phosphorylation of ATP synthase, DNA and RNA helicases, and proteins important for cell division and protein synthesis. Collectively, our results indicate that Stp1 is important for appropriate regulation of Stk1 function, hemolysin activity, autolysis, and GBS virulence. PMID- 22081607 TI - DHHC5 protein palmitoylates flotillin-2 and is rapidly degraded on induction of neuronal differentiation in cultured cells. AB - Post-translational palmitoylation of intracellular proteins is mediated by protein palmitoyltransferases belonging to the DHHC family, which share a common catalytic Asp-His-His-Cys (DHHC) motif. Several members have been implicated in neuronal development, neurotransmission, and synaptic plasticity. We previously observed that mice homozygous for a hypomorphic allele of the ZDHHC5 gene are impaired in context-dependent learning and memory. To identify potentially relevant protein substrates of DHHC5, we performed a quantitative proteomic analysis of stable isotope-labeled neuronal stem cell cultures from forebrains of normal and DHHC5-GT (gene-trapped) mice using the bioorthogonal palmitate analog 17-octadecynoic acid. We identified ~300 17-octadecynoic acid-modified and hydroxylamine-sensitive proteins, of which a subset was decreased in abundance in DHHC5-GT cells. Palmitoylation and oligomerization of one of these proteins (flotillin-2) was abolished in DHHC5-GT neuronal stem cells. In COS-1 cells, overexpression of DHHC5 markedly stimulated the palmitoylation of flotillin-2, strongly suggesting a direct enzyme-substrate relationship. Serendipitously, we found that down-regulation of DHHC5 was triggered within minutes following growth factor withdrawal from normal neural stem cells, a maneuver that is used to induce neural differentiation in culture. The effect was reversible for up to 4 h, and degradation was partially prevented by inhibitors of ubiquitin-mediated proteolysis. These findings suggest that protein palmitoylation can be regulated through changes in DHHC PAT levels in response to differentiation signals. PMID- 22081608 TI - Identification of novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease. AB - Primate-specific genes and isoforms could provide insight into human brain diseases. Our bioinformatic analysis revealed that there are possibly five isoforms of human GDNF gene with different pre- and pro-regions by inter- and intra-exon splicing. By using TaqMan primer probe sets, designed between exons, we verified the expression of all isoforms. Furthermore, a novel GDNFOS gene was found to be transcribed from the opposite strand of GDNF gene. GDNFOS gene has four exons that are spliced into different isoforms. GDNFOS1 and GDNFOS2 are long noncoding RNAs, and GDNFOS3 encodes a protein of 105 amino acids. To study human GDNF and GDNFOS regulation in neurodegenerative diseases, the protein and mRNA levels were measured by Western blot and RT-quantitative PCR, respectively, in postmortem middle temporal gyrus (MTG) of Alzheimer disease (AD) and Huntington disease (HD) patients in comparison with those of normal controls. In the MTG of AD patients, the mature GDNF peptide was down-regulated; however, the transcript of GDNF isoform from human exon 2 was up-regulated, whereas that of the conserved isoform from exon 1 remained unchanged in comparison with those of normal controls. In contrast, the mature GDNF peptide and the isoform mRNA levels were not changed in the MTG of HD. The findings of novel GDNF and GDNFOS isoforms and differences in tissue expression patterns dysregulated in AD brains may further reveal the role of endogenous GDNF in human brain diseases. PMID- 22081609 TI - Fat-derived factor omentin stimulates endothelial cell function and ischemia induced revascularization via endothelial nitric oxide synthase-dependent mechanism. AB - Obesity-related diseases are associated with vascular dysfunction and impaired revascularization. Omentin is a fat-derived secreted protein, which is down regulated in association with obese complications. Here, we investigated whether omentin modulates endothelial cell function and revascularization processes in vitro and in vivo. Systemic delivery of an adenoviral vector expressing omentin (Ad-omentin) enhanced blood flow recovery and capillary density in ischemic limbs of wild-type mice in vivo, which were accompanied by increased phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). In cultured human umbilical vein endothelial cells (HUVECs), a physiological concentration of recombinant omentin protein increased differentiation into vascular-like structures and decreased apoptotic activity under conditions of serum starvation. Treatment with omentin protein stimulated the phosphorylation of Akt and eNOS in HUVECs. Inhibition of Akt signaling by treatment with dominant-negative Akt or LY294002 blocked the stimulatory effects of omentin on differentiation and survival of HUVECs and reversed omentin-stimulated eNOS phosphorylation. Pretreatment with the NOS inhibitor also reduced the omentin-induced increase in HUVEC differentiation and survival. Omentin protein also stimulated the phosphorylation of AMP-activated protein kinase in HUVECs. Transduction with dominant-negative AMP-activated protein kinase diminished omentin-induced phosphorylation of Akt and omentin-stimulated increase in HUVEC differentiation and survival. Of importance, in contrast to wild-type mice, systemic administration of Ad-omentin did not affect blood flow in ischemic muscle in eNOS-deficient mice in vivo. These data indicate that omentin promotes endothelial cell function and revascularization in response to ischemia through its ability to stimulate an Akt eNOS signaling pathway. PMID- 22081610 TI - Aquaporin-9 protein is the primary route of hepatocyte glycerol uptake for glycerol gluconeogenesis in mice. AB - It has been hypothesized that aquaporin-9 (AQP9) is part of the unknown route of hepatocyte glycerol uptake. In a previous study, leptin receptor-deficient wild type mice became diabetic and suffered from fasting hyperglycemia whereas isogenic AQP9(-/-) knock-out mice remained normoglycemic. The reason for this improvement in AQP9(-/-) mice was not established before. Here, we show increased glucose output (by 123% +/- 36% S.E.) in primary hepatocyte culture when 0.5 mM extracellular glycerol was added. This increase depended on AQP9 because it was absent in AQP9(-/-) cells. Likewise, the increase was abolished by 25 MUM HTS13286 (IC(50) ~ 2 MUM), a novel AQP9 inhibitor, which we identified in a small molecule library screen. Similarly, AQP9 deletion or chemical inhibition eliminated glycerol-enhanced glucose output in perfused liver preparations. The following control experiments suggested inhibitor specificity to AQP9: (i) HTS13286 affected solute permeability in cell lines expressing AQP9, but not in cell lines expressing AQPs 3, 7, or 8. (ii) HTS13286 did not influence lactate- and pyruvate-dependent hepatocyte glucose output. (iii) HTS13286 did not affect glycerol kinase activity. Our experiments establish AQP9 as the primary route of hepatocyte glycerol uptake for gluconeogenesis and thereby explain the previously observed, alleviated diabetes in leptin receptor-deficient AQP9(-/-) mice. PMID- 22081611 TI - Insight into molecular basis of curing of [PSI+] prion by overexpression of 104 kDa heat shock protein (Hsp104). AB - Yeast prions are a powerful model for understanding the dynamics of protein aggregation associated with a number of human neurodegenerative disorders. The AAA+ protein disaggregase Hsp104 can sever the amyloid fibrils produced by yeast prions. This action results in the propagation of "seeds" that are transmitted to daughter cells during budding. Overexpression of Hsp104 eliminates the [PSI+] prion but not other prions. Using biochemical methods we identified Hsp104 binding sites in the highly charged middle domain of Sup35, the protein determinant of [PSI+]. Deletion of a short segment of the middle domain (amino acids 129-148) diminishes Hsp104 binding and strongly affects the ability of the middle domain to stimulate the ATPase activity of Hsp104. In yeast, [PSI+] maintained by Sup35 lacking this segment, like other prions, is propagated by Hsp104 but cannot be cured by Hsp104 overexpression. These results provide new insight into the enigmatic specificity of Hsp104-mediated curing of yeast prions and sheds light on the limitations of the ability of Hsp104 to eliminate aggregates produced by other aggregation-prone proteins. PMID- 22081612 TI - Ataxin-3 deubiquitination is coupled to Parkin ubiquitination via E2 ubiquitin conjugating enzyme. AB - We reported previously that parkin, a Parkinson disease-associated E3 ubiquitin ligase interacts with ataxin-3, a deubiquitinating enzyme associated with Machado Joseph disease. Ataxin-3 was found to counteract parkin self-ubiquitination both in vitro and in cells. Moreover, ataxin-3-dependent deubiquitination of parkin required the catalytic cysteine 14 in ataxin-3, although the precise mechanism remained unclear. We report here that ataxin-3 interferes with the attachment of ubiquitin (Ub) onto parkin in real-time during conjugation but is unable to hydrolyze previously assembled parkin-Ub conjugates. The mechanism involves an ataxin-3-dependent stabilization of the complex between parkin and the E2 Ub conjugating enzyme, which impedes the efficient charging of the E2 with Ub. Moreover, within this complex, the transfer of Ub from the E2 is diverted away from parkin and onto ataxin-3, further explaining how ataxin-3 deubiquitination is coupled to parkin ubiquitination. Taken together, our findings reveal an unexpected convergence upon the E2 Ub-conjugating enzyme in the regulation of an E3/deubiquitinating enzyme pair, with important implications for the function of parkin and ataxin-3, two proteins responsible for closely related neurodegenerative diseases. PMID- 22081615 TI - Metabolic syndrome in childhood from impaired carbohydrate metabolism to nonalcoholic fatty liver disease. AB - Compelling evidence supports the concept that nonalcoholic fatty liver disease (NAFLD) represents the hepatic component of metabolic syndrome (MetS). Intrahepatic fat seems to predict more strongly than does visceral adiposity an individual's cardiovascular risk and the likelihood that metabolic abnormalities are present in youth. Young individuals with fatty liver are more insulin resistant and present with a higher prevalence of metabolic abnormalities than do individuals without intrahepatic fat accumulation. They also present with a certain endothelial dysfunction and greater carotid intima-media thickness. Conversely, youth with MetS seem to have an increased risk of developing liver inflammation, a condition termed nonalcoholic steatohepatitis (NASH), and fibrosis. In the context of MetS, the liver is central in that it can drive both hepatic and systemic insulin resistance, trigger low-grade inflammation, and promote atherogenic processes. In the context of MetS, NAFLD and altered carbohydrate metabolism track from childhood to adulthood. Thus, prevention, recognition, and effective treatment of these two abnormalities may limit the burden of morbidity and mortality associated with obesity and may delay onset of cardiovascular disease in early adulthood. The present review aims at systematically presenting evidence of the critical interplay of fatty liver and altered glucose metabolism in youth. It attempts to provide pathogenetic explanations for such an association and the rationale for its treatment, with particular regard to nutritional interventions. Key teaching points: Overweight and obese youth should be screened for fatty liver disease once after puberty by liver function tests and ultrasonography. Screening for fatty liver should be accurately performed in young patients with features of metabolic syndrome. Obese patients with fatty liver are at increased risk for altered glucose metabolism, thus they should undergo an oral glucose tolerance test. A nutritional and behavioral intervention aimed at achieving a permanent change of the lifestyle in patients and their parents is recommended. PMID- 22081614 TI - Health effects of mixed fruit and vegetable concentrates: a systematic review of the clinical interventions. AB - Diets rich in fruits and vegetables (FV) have been associated with a reduced risk of chronic disease, including cardiovascular disease. Unfortunately, public health campaigns to increase FV intake have had limited success. A number of mixed concentrated FV products have been studied, which may help certain individuals improve nutrient status. However, the possible health benefits of FV supplements have not been systematically reviewed. We, therefore, undertook a systematic search of MEDLINE and EMBASE to identify clinical interventions that examined the effect of commercially available concentrated mixed FV supplements on cardiovascular disease risk factors. Twenty-two reports, which used commercially available products, were identified. None of the studies reported any serious adverse effects. Overall, daily consumption of FV supplements significantly increased serum concentrations of the major antioxidant provitamins and vitamins found in plant foods (beta-carotene, vitamins C and E) and folate. Functional changes, such as reduced serum homocysteine and markers of protein, lipid, and DNA oxidation, were also reported; in addition, the health advantages on markers of inflammation, immunity, and endothelial function are promising. Limitations of the available studies were related to the diversity of studies conducted with respect to design and study population and the variability in the measured outcomes and assays utilized. While mixed FV supplements may serve as an efficacious complement for individuals who have difficulty achieving their daily FV intake requirement, further research on additional retail preparations is warranted. Key teaching points: Mixed fruit and vegetable supplements produced from plant foods may serve as an efficacious complement to the habitual diet in individuals who have suboptimal intake or variety of nutrient-dense fruits and vegetables. Current research indicates that fruit and vegetable concentrates significantly increase serum levels of antioxidant provitamins and vitamins (beta carotene, vitamins C and E) and folate and reduce homocysteine and markers of oxidative stress. Mechanistic studies and larger, randomized, placebo-controlled double-blind trials in both healthy and high-risk populations are necessary to better understand the health effects of these supplements. PMID- 22081616 TI - Lycium barbarum increases caloric expenditure and decreases waist circumference in healthy overweight men and women: pilot study. AB - BACKGROUND: Lycium barbarum (L. barbarum), a traditional Asian medicinal therapy for diabetes and other conditions, has been shown to increase metabolic rate and to reduce body-weight gains in rodent models, as well as to produce clinical improvements in general feelings of well-being including energy level. OBJECTIVE: To investigate the impact of L. barbarum consumption on (1) caloric expenditure and (2) changes in morphometric parameters (waist circumference) in healthy human adults. METHOD: Two separate randomized, double-blind, placebo-controlled, small clinical studies were conducted using a standardized L. barbarum fruit juice, GoChi, and assessing its effects on (1) resting metabolic rate (RMR) and postprandial energy expenditure (PPEE) as measured by indirect calorimetry after single-bolus intake of 3 doses of L. barbarum (30, 60, and 120 ml) and placebo; and (2) waist circumference and other morphometric changes in a 14-day intervention trial (120-ml daily intake) in the subjects (age = 34 years, body mass index = 29 kg/m(2)). RESULTS: (1) A single bolus of L. barbarum intake increased PPEE 1 through 4 hours postintake over the baseline level in a dose dependent manner and was significantly higher than the placebo group by 10% at 1 hour postintake of 120 ml (p < 0.05). (2) In a 14-day intervention trial, L. barbarum was found to significantly decrease waist circumference by 5.5 +/- 0.8 cm (n = 15) compared with the preintervention measurements and placebo group at postintervention day 15 (p < 0.01). By contrast, the changes in the placebo group (n = 14) from preinterventions was 0.9 +/- 0.8 cm, which was not statistically significant. CONCLUSIONS: These results show that L. barbarum consumption increases metabolic rate and reduces the waist circumference, relative to placebo treated control subjects. PMID- 22081613 TI - Mechanism of start site selection by RNA polymerase II: interplay between TFIIB and Ssl2/XPB helicase subunit of TFIIH. AB - TFIIB is essential for transcription initiation by RNA polymerase II. TFIIB also cross-links to terminator regions and is required for gene loops that juxtapose promoter-terminator elements in a transcription-dependent manner. The Saccharomyces cerevisiae sua7-1 mutation encodes an altered form of TFIIB (E62K) that is defective for both start site selection and gene looping. Here we report the isolation of an ssl2 mutant, encoding an altered form of TFIIH, as a suppressor of the cold-sensitive growth defect of the sua7-1 mutation. Ssl2 (Rad25) is orthologous to human XPB and is a member of the SF2 family of ATP dependent DNA helicases. The ssl2 suppressor allele encodes an arginine replacement of the conserved histidine residue (H508R) located within the DEVH containing helicase domain. In addition to suppressing the TFIIB E62K growth defect, Ssl2 H508R partially restores both normal start site selection and gene looping. Moreover, Ssl2, like TFIIB, associates with promoter and terminator regions, and the diminished association of TFIIB E62K with the PMA1 terminator is restored by the Ssl2 H508R suppressor. These results define a novel, functional interaction between TFIIB and Ssl2 that affects start site selection and gene looping. PMID- 22081617 TI - Central obesity predicts non-Hodgkin's lymphoma mortality and overall obesity predicts leukemia mortality in adult Taiwanese. AB - OBJECTIVE: Obesity may increase the risk of neoplasia, including that of the lymphohematopoietic system. In a large Taiwanese cohort, we have evaluated whether body fat and its distribution is associated with non-Hodgkin's lymphoma (NHL) and leukemia mortalities. METHODS: During 1997-2007 in Taiwan, 383,956 subjects aged 19-98 years without any cancer history were obtained through a health screening center and followed up for a median of 7.2 years. Unit records were linked to the national death registry; ICD-9 codes were used to identify 143 NHL and 73 leukemia deaths. Objectively, height, weight, and waist circumference data were measured to calculate body mass index (BMI) and central obesity status. Based on World Health Organization criteria modified for Asia and Taiwan, BMI was classified to <18.5, 18.5-23.9, 24-26.9, and >= 27 kg/m(2). Waist circumference >= 90 cm in men and >= 80 cm in women was defined as central obesity. Cox proportional hazard regression models were adjusted for possible confounders including gender, age, education, smoking status, alcohol consumption, physical activity, and clinic location. RESULTS: BMI was not associated with NHL deaths, although the trend was significant, but central obesity with adjustment was (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.27-2.75) compared with non-centrally obese subjects. BMI, but not central obesity, was associated with leukemia mortality (HR = 1.93, 95% CI = 1.00-3.75). CONCLUSIONS: An increased risk for NHL with increased abdominal fatness and more so with lower BMI is apparent in Taiwanese; this may indicate that metabolically localized and proinflammatory fat is important. For leukemia, where most is myeloid leukemia, increased general fatness is evidently a risk with Taiwanese ethnicity. PMID- 22081618 TI - Mate tea (Ilex paraguariensis) improves glycemic and lipid profiles of type 2 diabetes and pre-diabetes individuals: a pilot study. AB - OBJECTIVES: Yerba mate (Ilex paraguariensis) infusions have been shown to reduce plasma glucose in animals and serum lipids in humans. The aim of this study was to evaluate the effects of roasted mate tea consumption, with or without dietary counseling, on the glycemic and lipid profiles of individuals with type 2 diabetes mellitus (T2DM) or pre-diabetes. METHODS: Twenty-nine T2DM and 29 pre diabetes subjects were divided into 3 groups: mate tea, dietary intervention, and mate tea and dietary intervention. Individuals drank 330 mL of roasted mate tea 3 times a day and/or received nutritional counseling over 60 days. Blood samples were collected and food intake was assessed at baseline and after 20, 40, and 60 days of treatments. RESULTS: Mate tea consumption decreased significantly the levels of fasting glucose (25.0 mg/dL), glycated hemoglobin A(1c) (HbA(1c)) (0.85%), and low-density lipoprotein cholesterol (LDL-c) (13.5 mg/dL) of T2DM subjects (p < 0.05); however, it did not change the intake of total energy, protein, carbohydrate, cholesterol, and fiber. In pre-diabetes individuals, mate tea consumption combined with nutritional counseling diminished significantly the levels of LDL-c (11 mg/dL), non-high-density lipoprotein cholesterol (HDL-c) (21.5 mg/dL), and triglycerides (53.0 mg/dL) (p < 0.05). Individuals of this group decreased significantly their consumption of total fat (14%), cholesterol (28%), and saturated (23.8%) and monounsaturated (28.0%) fatty acids, and increased their fiber intake by 35% (p < 0.05). CONCLUSIONS: Mate tea consumption improved the glycemic control and lipid profile of T2DM subjects, and mate tea consumption combined with nutritional intervention was highly effective in decreasing serum lipid parameters of pre-diabetes individuals, which may reduce their risk of developing coronary disease. PMID- 22081619 TI - Favorable effect of short-term lifestyle intervention on human paraoxonase-1 activity and adipokine levels in childhood obesity. AB - OBJECTIVE: The prevalence of obesity is increasing in adult and child populations throughout the world. Childhood obesity has a great impact on adult cardiovascular morbidity and mortality; treatment of this pathological state is important given the significant health consequences. We investigated the effect of short-term lifestyle changes on the alteration of human serum paraoxonase-1 (PON1) activities, leptin, adiponectin, E-selectin, and asymmetric dimethylarginine (ADMA) as atherogenic and antiatherogenic factors in obese children. PON1 protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low density lipoprotein (LDL) and therefore may protect against atherosclerosis. METHODS: A total of 23 white obese and overweight children (age, 11.43 +/- 1.78 years; 8 girls, 15 boys) participated in a 2-week long lifestyle camp based on a diet and exercise program. Overweight and obesity were defined according to the national body mass index (BMI) reference tables for age and sex. RESULTS: After a 2-week-long supervised diet and aerobic exercise program, obese children had significantly lower leptin (55.02 +/- 33.42 ng/ml vs 25.37 +/- 19.07 ng/ml; p < 0.0001), ADMA (0.68 +/- 0.15 MUmol/l vs 0.55 +/- 0.16 MUmol/l; p < 0.01), and E-selectin levels (67.19 +/- 30.35 ng/ml vs 46.51 +/- 18.40 ng/ml; p < 0.0001), whereas they had significantly higher PON1 paraoxonase activity (110.48 +/- 72.92 U/l vs 121.75 +/- 93.48 U/l; p < 0.05) besides the antiatherogenic alteration of the lipid profile and significant weight change (70.32 +/- 19.51 kg vs 67.01 +/- 18.75 kg, p < 0.0001; BMI, 28.95 +/- 5.05 kg/m(2) vs 27.43 +/- 4.82 kg/m(2), p < 0.0001). Adiponectin and PON1 arylesterase activity did not change significantly. CONCLUSIONS: Our investigation suggests that modifications in dietary habits and physical activity induce antiatherogenic changes in childhood obesity. These findings emphasize the major role of primary prevention and nonpharmaceutical treatment of childhood obesity through lifestyle changes based on diet and increased physical activity. PMID- 22081620 TI - Riboflavin status and its association with serum hs-CRP levels among clinical nurses with depression. AB - OBJECTIVE: The objective of present study was to assess the relationship between the dietary intake and blood status of riboflavin and the prevalence of systemic inflammation among both depressed and nondepressed nurses. METHODS: This was a cross-sectional study on 98 female clinical nurses (45 depressed and 53 nondepressed subjects). Depression status was assessed using the Beck Depression Inventory. We assessed dietary intake of riboflavin using 3-day 24-hour recalls. The serum concentrations of high-sensitive C-reactive protein (hs-CRP) were also measured. Riboflavin status was assessed as the erythrocyte glutathione reductase activity coefficient (EGRAC). RESULTS: Marginal riboflavin deficiency was more prevalent in depressed subjects (P = 0.028). The results of the dietary intake and status of riboflavin were classified to 3 tertiles of serum hs-CRP levels. In both nondepressed and depressed subjects, there was no significant difference between hs-CRP tertiles in dietary intakes of riboflavin, EGRAC, or riboflavin deficiencies. CONCLUSION: This study showed a higher prevalence of marginal riboflavin deficiency in depressed subjects. We found no association between dietary intake and status of riboflavin with low-grade systematic inflammation in nondepressed and depressed clinical nurses. PMID- 22081621 TI - Autism rates associated with nutrition and the WIC program. AB - OBJECTIVES: Autism rates in the United States are increasing at a rate of 15% per year. Autistic children are diagnosed by age 3 when they have problems communicating and interacting socially. This study uses nutritional epidemiology and an ecologic study design to link the possible cause of autism to nutrition by creating autism rates for the 50 states of America and comparing them with published measures of infant nutrition such as duration of exclusive breast feeding and participation in the Women, Infants, and Children (WIC) program. The percentage of infants with measles, mumps, and rubella (MMR) inoculations was also compared with the autism rates. Study DESIGN: Autism rates for each state were established. The percentage of infants who participate in the WIC program for low-income families was calculated for each of the 50 states as well as 21 New Jersey and 30 Oregon counties and compared with their autism rates. An ecologic study design with correlation coefficients is limited, but it is useful for generating hypotheses to be tested. RESULTS: The states with the highest WIC participation have significantly lower autism rates (p < 0.02). A similar pattern was observed in 21 New Jersey counties (p < 0.02) and 30 Oregon counties (p < 0.05). In contrast, there was a direct correlation with the increasing percentage of women exclusively breast-feeding from 2000-2004 (p < 0.001). Infants who were solely breast-fed had diets that contained less thiamine, riboflavin, and vitamin D than the minimal daily requirements (MDR). There was no correlation of MMR inoculations with the autism rate. CONCLUSION: The mothers who are exclusively breast-feeding should also continue their prenatal vitamins or their equivalent and make better dietary choices. These results suggest that autism may be nutritionally related to a possible deficiency of riboflavin or the cognitive vitamins such as thiamine or vitamin D. However, due to an ecologic study design there is a potential for fallacy because individuals were not examined. The results suggest the need for a robust observational study in advance of, and to confirm the need for, an intervention study. PMID- 22081625 TI - Polyclonal B lymphocytosis with binucleated lymphocytes in a man. PMID- 22081626 TI - Transplantation of porcine umbilical cord matrix mesenchymal stem cells in a mouse model of Parkinson's disease. AB - The present study compared mesenchymal stem cells derived from umbilical cord matrix (UCM-MSCs) with bone marrow (BM-MSCs) of miniature pigs on their phenotypic profiles and ability to differentiate in vitro into osteocytes, adipocytes and neuron-like cells. This study further evaluated the therapeutic potential of UCM-MSCs in a mouse Parkinson's disease (PD) model. Differences in expression of some cell surface and cytoplasm specific markers were evident between UCM-MSCs and BM-MSCs. However, the expression profile indicated the primitive nature of UCM-MSCs, along with their less or non-immunogenic features, compared with BM-MSCs. In vitro differentiation results showed that BM-MSCs had a higher tendency to form osteocytes and adipocytes, whereas UCM-MSCs possessed an increased potential to transform into immature or mature neuron-like cells. Based on these findings, UCM-MSCs were transplanted into the right substantia nigra (SN) of a mouse PD model. Transplantation of UCM-MSCs partially recovered the mouse PD model by showing an improvement in basic motor behaviour, as assessed by rotarod and bridge tests. These observations were further supported by the expression of markers, including nestin, tyrosine hydroxylase (TH), neuronal growth factor (NGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6), at the site of cell transplantation. Our findings of xenotransplantation have collectively suggested the potential utility of UCM-MSCs in developing viable therapeutic strategies for PD. PMID- 22081627 TI - Hypoxia-inducible factor-1alpha protein negatively regulates load-induced bone formation. AB - Mechanical loads induce profound anabolic effects in the skeleton, but the molecular mechanisms that transduce such signals are still poorly understood. In this study, we demonstrate that the hypoxia-inducible factor-1alpha (Hif-1alpha) is acutely up-regulated in response to exogenous mechanical stimuli secondary to prostanoid signaling and Akt/mTOR (mammalian target of rapamycin) activation. In this context, Hif-1alpha associates with beta-catenin to inhibit Wnt target genes associated with bone anabolic activity. Mice lacking Hif-1alpha in osteoblasts and osteocytes form more bone when subjected to tibia loading as a result of increased osteoblast activity. Taken together, these studies indicate that Hif 1alpha serves as a negative regulator of skeletal mechanotransduction to suppress load-induced bone formation by altering the sensitivity of osteoblasts and osteocytes to mechanical signals. PMID- 22081629 TI - Defra seeks views on controlling an outbreak of rabies. PMID- 22081630 TI - Parliamentary committees to examine AHVLA's plans for lab services. PMID- 22081628 TI - Effect of double growth factor release on cartilage tissue engineering. AB - The effects of double release of insulin-like growth factor I (IGF-I) and growth factor beta1 (TGF-beta1) from nanoparticles on the growth of bone marrow mesenchymal stem cells and their differentiation into cartilage cells were studied on PLGA scaffolds. The release was achieved by using nanoparticles of poly(lactic acid-co-glycolic acid) (PLGA) and poly(N-isopropylacrylamide) (PNIPAM) carrying IGF-I and TGF-beta1, respectively. On tissue culture polystyrene (TCPS), TGF-beta1 released from PNIPAM nanoparticles was found to have a significant effect on proliferation, while IGF-I encouraged differentiation, as shown by collagen type II deposition. The study was then conducted on macroporous (pore size 200-400 um) PLGA scaffolds. It was observed that the combination of IGF-I and TGF-beta1 yielded better results in terms of collagen type II and aggrecan expression than GF-free and single GF-containing applications. It thus appears that gradual release of a combination of growth factors from nanoparticles could make a significant contribution to the quality of the engineered cartilage tissue. PMID- 22081631 TI - Equestrian excellence acknowledged. PMID- 22081632 TI - Tracking rare tigers to help in conservation. PMID- 22081633 TI - Survey investigates pet owners' awareness of preventative medicine. PMID- 22081634 TI - Farm dog neutering scheme takes off. PMID- 22081635 TI - Focus on performance at 50th BEVA congress. PMID- 22081636 TI - Plotting how the land lies in livestock holdings. PMID- 22081637 TI - Potential of diagnostic markers in sustainable control of cattle parasites. PMID- 22081638 TI - British Veterinary Association annual general meeting, 2011. PMID- 22081639 TI - Non-healing hoof lesions in dairy cows. PMID- 22081640 TI - Human and veterinary general practice. PMID- 22081641 TI - Changes to the PDSA's charitable objectives. PMID- 22081642 TI - Veterinary specialists and fellows of the Royal College. PMID- 22081643 TI - Celebrating 60 years of the African Union - Interafrican Bureau for Animal Resources. PMID- 22081644 TI - Bluetongue-associated clinical signs in Israel. PMID- 22081645 TI - Insulin suppresses ghrelin-induced calcium signaling in neuropeptide Y neurons of the hypothalamic arcuate nucleus. AB - Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC) play an important role in feeding regulation. Plasma levels of ghrelin and insulin show reciprocal dynamics before and after meals. We hypothesized that ghrelin and insulin also exert reciprocal effects on ARC NPY neurons. Cytosolic Ca2+ concentration ([Ca2+](i)) was measured by fura-2 microfluorometry in single neurons isolated from ARC of adult rats, followed by immunocytochemical identification of NPY neurons. Ghrelin at 10-10 M increased [Ca2+](i) in isolated ARC neurons, and co-administration of insulin concentration-dependently suppressed the ghrelin-induced [Ca2+](i) increases. Insulin at 10-16 M, 10-14 M, 10-12 M and 10-10 M counteracted ghrelin action in 26%, 41%, 61% and 53% of ghrelin-responsive neurons, respectively, showing a maximal effect at 10-12 M, the estimated postprandial concentration of insulin in the brain. The majority (>70%) of the ghrelin-activated insulin-inhibited neurons were shown to contain NPY. Double-immunohistochemistry revealed that 85% of NPY neurons in ARC express insulin receptors. These data demonstrate that insulin directly interacts with ARC NPY neurons and counteracts ghrelin action. Our results suggest that postprandial increase in plasma insulin/ghrelin ratio and insulin inhibition of ghrelin action on ARC NPY neurons cooperate to effectively inhibit the neuron activity and terminate feeding. PMID- 22081646 TI - Role of medial prefrontal cortex dopamine in age differences in response to amphetamine in rats: locomotor activity after intra-mPFC injections of dopaminergic ligands. AB - Changes in medial prefrontal cortex (mPFC) dopamine receptor expression and in mPFC projections to the nucleus accumbens in adolescence suggest that there may be age differences in the regulation of drug-related behavior by the mPFC. The age-specific role of prelimbic D1 dopamine receptors on amphetamine-induced locomotor activity was investigated. In experiment 1, rats aged postnatal day 30 (P30), P45, and P75, corresponding to early and late adolescence and adulthood, were given an injection of D1 and D2 antagonists into the prelimbic mPFC before a systemic injection of 1.5 mg/kg of amphetamine and locomotor activity was recorded. In experiment 2, effects of intra-prelimbic injections of a D1 agonist and antagonist on locomotor activity produced by a lower dose (0.5 mg/kg) of amphetamine were investigated. D2 receptor antagonist did not alter amphetamine induced activity, whereas the D1 receptor antagonist reduced activity produced by 1.5 mg/kg of amphetamine more in P30 than in P45 and P75 rats. In addition, D1 agonist enhanced the locomotor activating effects of 0.5 mg/kg of amphetamine in adolescent rats and decreased activity in adult rats. These results suggest that insufficient activation of mPFC D1 receptors may underlie the reduced activity at the low dose of amphetamine in early adolescent compared to adult rats. PMID- 22081647 TI - Clinical skills assessment: comparison of student and examiner assessment in an objective structured clinical examination. AB - BACKGROUND: Learning of basic clinical skills is introduced in Years 1 and 2 of the MBBS Program; the Aga Khan University, Pakistan, through a structured Clinical Skills Teaching program. Acquisition of competence in performing these skills is assessed through use of the Objective Structured Clinical Examination (OSCE). Self-assessment is defined broadly as the involvement of learners in judging whether or not learner-identified standards have been met. OBJECTIVE: Compared Year 2 students' self-assessment of clinical skills with examiners' assessment of performance in an OSCE using a standard rating scale. METHODS: A self-assessment questionnaire was completed by all Year 2 students immediately after the OSCE. Students assessed their performance at three stations, using a performance rating scale. Examiners observed and evaluated the students during history-taking and physical examination using the same rating scale. RESULTS: There were significant positive correlations between examiners' assessments of performance and students' self-assessed ratings in taking consent, obtaining demographic information, history of presenting problems and summarization. Significant differences were observed in pre-procedural skills, comment on prostate, liver palpation percussion and spleen percussion. CONCLUSIONS: Findings highlight the strengths and weaknesses in clinical competence at the end of Year 2 and provide a direction to improve the gaps in the Clinical Skills Teaching program. PMID- 22081648 TI - Changing language: response to a change in conducting weekly rounds. PMID- 22081649 TI - The effectiveness of AGU-MCAT in predicting medical student performance in year one of the College of Medicine of the Arabian Gulf University. AB - INTRODUCTION: To graduate good doctors, medical schools should adopt proper student procedures to select among applicant students. When selecting students, many medical colleges focus solely on their academic achievement on high school examinations, which do not reflect all, important attributes of student. For several years, the College of Medicine and Medical Sciences of the Arabian Gulf University has introduced and administered the AGU-MCAT (Arabian Gulf University Medical College Assessment Test) for screening student applicants. This study aimed to assess the ability of the AGU-MCAT to predict students' performance during their first year college study, as an example of one school's multi dimensional admissions screening process. METHODS: The AGU-MCAT is made up of three parts, including a written test on science, a test of students' English language skills and an interview. In the first part, students' science knowledge is tested with 100 multiple choice questions. The English exam assesses students. English reading and listening skills. Lastly, students are interviewed by two faculty members and one senior student to assess their personal qualities. The 138 students who passed the AGU-MCAT in September 2008 and matriculated in the school were studied. Their performance during Year One including their performance on exams in the various disciplines was compared to their achievement on the three AGU-MCAT components. RESULTS: AGU-MCAT's total mark and its science component had the highest linear relationship to students' performance in the various disciplines in Year One, while the strongest predictor of students' performance at the end of Year One was the AGU-MCAT's science test (R2=45.5%). Students' grades in high school did not predict their achievement in Year One. CONCLUSION: The AGU-MCAT used to screen applicants to the school also predicts students' performance during their first year of medical school. PMID- 22081650 TI - Inappropriate drug donations: what has happened since the 1999 WHO guidelines? AB - CONTEXT: Drug donations to developing countries may be part of medical relief operations in acute emergencies, development aid in non-emergency situations, or a corporate donations programme. After a number of documented inappropriate drug donations, the World Health Organization developed the 'Guidelines for Drug Donations', with the second and final version published in 1999. OBJECTIVES: We reviewed the medical literature on drug donations since the Guidelines publication in 1999. DESIGN: Literature was retrieved from PubMed and other on line databases as well as from relevant websites providing medical literature for use in developing countries. We considered the following donations to be inappropriate: (i) essential drugs in excessive quantities; (ii) mixed unused drugs (unsorted medicines and free samples); and (iii) drug dumping (large quantities of useless medicines). RESULTS: We retrieved 25 publications dated after 1999, including 20 and 5 from the scientific literature and 'grey' literature (technical reports, working papers), respectively. New information concerned emergencies in East Timor, Mozambique, El Salvador, Gujarat State (India), Aceh (Indonesia) and Sri Lanka. Except for East Timor and Gujarat, inappropriate donations still occurred, accounting for 85%, 37%, 70% and 80% of donations in Mozambique, El Salvador, Aceh and Sri Lanka, respectively. Very little information was found on drug donations in non-emergency situations. CONCLUSION: There are few recent reports on the compliance of drug donations with the World Health Organization guidelines. For emergency situations, there is still room for improvement. Drug donations in non-emergency situations need to be evaluated. A reform of drug donations policy is needed. PMID- 22081651 TI - Feeling connected: technology and the support of clinical teachers in distant locations. AB - CONTEXT: This paper discusses a key finding arising from a qualitative research project which explored the provision of educational support to clinical teachers who were at least 100 kilometres distant from a university medical school. OBJECTIVES: We examined the preferences of clinical teachers in relation to the preferred use of technology as a medium for educational support. METHODS: A qualitative approach was used for which 19 participants were interviewed using structured interviews consisting of prepared open-ended questions. FINDINGS: All participants reported that they had a very positive association with the university. However, they overwhelmingly expressed a need to feel more strongly connected to the university and with each other. DISCUSSION: Although a trial of the videoconferencing technology had problems, there was still great potential to connect clinical teachers in a Community of Practice. PMID- 22081652 TI - A community health worker program for the prevention of malaria in eastern Kenya. AB - OBJECTIVE: To assess whether the development and implementation of a community health worker (CHW) project in rural Kenya was associated with an increase in knowledge about malaria and the use of insecticide-treated nets (ITNs) in children under five years of age. METHODS: A baseline knowledge and behavior questionnaire, adopted from the Kenyan Demographic Health Survey, was conducted in August 2007 by Kenyan health officials in 75 villages. Two CHWs were chosen from each village and trained in appropriate use of ITNs. The CHWs provided educational sessions and ITNs to mothers in their respective villages. A follow up survey was conducted in March 2008 of all families with children less than five years of age within randomly selected villages. The main questions addressed during the follow-up survey included knowledge about malaria and the practice of correctly using ITNs. FINDINGS: There were 267 surveys compiled for knowledge assessment before the intervention and 340 in the post-intervention analysis with an approximate 99% family participation rate. Of the families surveyed, 81% correctly knew the cause for malaria before the study and 93% after the CHW intervention (p < 0.01). Of those surveyed before the intervention, 70% owned and correctly used mosquito nets compared with 88% after the CHW intervention (p < 0.01). CONCLUSIONS: There was a significant increase in knowledge about malaria and use of ITNs after the implementation of the CHW program. PMID- 22081653 TI - Developing a self-directed workbook package for clinical skills training of medical students. PMID- 22081654 TI - Value of a health behavior change reflection assignment for health promotion learning. AB - INTRODUCTION: Health promotion is a recognized competency in the preparation and education of Addictions Counseling students. This qualitative study explores the value of a reflection assignment in an undergraduate health promotion course at the University of Lethbridge, Canada, towards developing Addictions Counseling students' health promotion competency. METHOD: In the course, students attempted a health behavior change of their own choosing, reflected on their experiences and completed a reflection paper. Thematic analysis was conducted on students' reflection papers (n=21) and on a transcript of a focus group with four students to generate a description of students' perceived value of the assignment for their learning, personal health, and future health promotion practice in the field of Addictions Counseling. RESULTS: Three themes marked students perceived increased capacity for healthy behavior and health promotion: (1) facilitating the change process; (2) integrating experiential and theoretical learning about health; and (3) growing as a health promotion practitioner and as a person with expanding capacity for health. DISCUSSION: This reflection assignment shows potential as both a learning process supporting future professional practice and as a tool for promoting health among undergraduate students. PMID- 22081655 TI - Changes in healthcare workers' knowledge about tuberculosis following a tuberculosis training programme. AB - BACKGROUND: In resource-limited countries, health policy makers and practitioners need to know whether healthcare workers have sufficient knowledge of tuberculosis and its management. OBJECTIVES: We conducted a study to: (1) measure knowledge changes among healthcare workers who participated in a tuberculosis training programme; and (2) make recommendations about future tuberculosis training for healthcare workers in the KwaZulu-Natal Department of Health. METHODS: A cross sectional study conducted in 2007 measured changes in tuberculosis knowledge of doctors, nurses and other healthcare workers after a training programme based on World Health Organization tuberculosis training modules. Data were collected before and after training using a self-administered, 98-item questionnaire covering eight components. RESULTS: A total of 267 healthcare workers, mean age 40.7 years, answered both pre- and post-training questionnaires. Mean total knowledge scores were low despite significant changes (p<0.001) from a pre training score of 59.5% to a post-training score of 66.5%. Nurses showed significant improvements in mean total knowledge scores (p<0.001) but had the lowest mean total knowledge score post-training, 63.2%. Doctors had significantly better pre-training (p<0.001) and post-training (p<0.001) mean total knowledge scores compared to nurses. CONCLUSIONS: Improvement in healthcare workers' overall knowledge of tuberculosis during a training programme was not clinically significant. Periodic field training and supervision should be considered to ensure tuberculosis knowledge improvements. PMID- 22081656 TI - Student-led peer-assisted learning: the Kuppi experience at the medical school of the University of Ruhuna in Sri Lanka. AB - CONTEXT: Peer-assisted learning (PAL) is described in the literature and is generally initiated with faculty assistance. The PAL process described here, called Kuppi classes, is exclusively organized and run by the students of the medical school of the University of Ruhuna. AIM: To explore students' experiences with Kuppi classes as a learning process. METHODS: A phenomenological research method with focus group discussions and in-depth interviews for data collection was used. Selection of students for the study ensured representation of genders, academic years of study, both Kuppi tutors and tutees, and both those who did and did not pass the prior examination in the medical school on the first attempt. FINDINGS: According to tutee and tutors, Kuppi was developed as a parallel process to fill in gaps in students' understanding and better explain unclear aspects of the formal curriculum. Within the Kuppi, students successfully use informality, familiarity and social bonds with one another to acquire the knowledge required for their examinations. CONCLUSIONS: This student-initiated PAL process appears to be succeeding for the students of our school. Some of their experiences may be helpful in implementing a PAL process or even improving the formal teaching processes in medical schools with similar academic, social and cultural environments. The need for a second, student-led curriculum should alert faculty to shortcomings in the formal curriculum and classes. PMID- 22081657 TI - Validation of the WHOQOL-BREF quality of life questionnaire for use with medical students. AB - PURPOSE: The purpose of the present study was to validate the use of the abbreviated version of the World Health Organization Quality of Life (WHOQOL BREF) questionnaire with medical students. METHODS: A sample of 274 medical students in their fourth and fifth years of study (80% response rate) completed the WHOQOL-BREF instrument. The four-domain factor structure of the questionnaire was tested using confirmatory factor analysis. A variety of other tests of reliability and validity were conducted. RESULTS: Goodness-of-fit indices from the confirmatory factor analysis were acceptable, and the factor structure of the WHOQOL-BREF was confirmed in this sample. Reliability was good, but three of the items showed strong ceiling effects. CONCLUSION: The WHOQOL-BREF is valid to use with medical students to assess health-related quality of life. Some items, such as those inquiring about pain and medication, may not be suitable for medical students or young people in general. PMID- 22081658 TI - Controlling errors to promote patient safety. PMID- 22081659 TI - Change in medical students' readiness for self-directed learning after a partially problem-based learning first year curriculum at the KIST medical college in Lalitpur, Nepal. AB - INTRODUCTION: Modern medical education and the requirement for lifelong learning place increasing emphasis on self-directed learning. Studies have not been done on readiness for self-directed learning (SDL) among medical students in Nepal. The present study was carried out to (1) measure and compare readiness for SDL among medical students, and (2) note differences in readiness for SDL according to students' personal characteristics at the beginning and end of the first year of the MBBS course for medical students at the KIST Medical College in Nepal. METHODS: The study was done using the Self-directed Learning Readiness Scale. Respondents' agreement with each of forty statements pertinent to self-directed learning readiness using a modified Likert-type scale was noted. The mean total and scores on the subcategories 'self-management', 'desire for learning' and 'self-control' were calculated and compared across subgroups of respondents and in January and August 2010 using appropriate parametric and non-parametric tests (p<0.05). RESULTS: All 100 students participated in January while 90 participated in August. The mean scores varied with certain demographic and background characteristics. The mean total score increased from 152.7 to 157.3 while the self-management score increased significantly from 48.6 to 50.2 from January to August. There were small increases in the mean desire for learning scores from 46.9 to 47.7 and in the self-control scores from 58 to 59 from January to August, but not in other scores. CONCLUSIONS: Self-directed learning scores were lower among these Nepalese students than reported elsewhere in the literature. Total scores and self-management scores improved at the end of the first year, but not scores on desire for learning and self-control. PMID- 22081660 TI - Orienting incoming medical students to the process of PBL through video. PMID- 22081661 TI - Evaluation of an interprofessional education communication skills initiative. AB - CONTEXT: Interprofessional education of pre-licensure students is viewed as an important precursor to developing healthcare professionals who are able to work collaboratively. OBJECTIVES: This study conducted a program evaluation of an innovative interprofessional communication skills initiative which incorporated problem-based learning, cooperative learning and standardized patients. METHODS: The communication skills session consisted of a three-hour, faculty facilitated, interactive format in which teams of five to eight students met to conduct an interview with a standardized patient and develop an interprofessional care plan. The program evaluation included measures of satisfaction, the Interprofessional Education Perception Scale (IEPS), the Readiness for Interprofessional Learning Scale (RIPLS), focus groups and individual interviews. FINDINGS: A total of 96 students from medical, nursing, physiotherapy, occupational therapy, midwifery, physician assistant and pharmacy programs self-selected to participate in the evaluation. Students rated their satisfaction with the communications skills sessions highly. There were small but statistically significant changes pre- and post-session in the IEPS. Qualitative analyses revealed that students perceived that they had learned about each others' scope of practice and built confidence in their communication skills. The skill of the facilitator and preparation for the experience were perceived to promote the success. DISCUSSION AND CONCLUSION: The demand for experiential events which provide students with the skills required to interact effectively in healthcare teams is likely to continue with the growing awareness of the need for interprofessional education. A learning experience which incorporates standardized patients and feedback from faculty facilitators can promote authentic interprofessional learning, and develop students' confidence to communicate in a team environment. PMID- 22081662 TI - Formative versus summative assessment. PMID- 22081664 TI - Continuing progress in primary healthcare education. PMID- 22081666 TI - Online optical coherence tomography during subthreshold laser irradiation. AB - PURPOSE: To investigate the role of real-time optical coherence tomography (OCT) in the detection of standard and nonvisible subthreshold laser irradiation. METHODS: We used an integrated platform consisting of a slit-lamp, a digital camera, a slit-lamp mounted OCT, and a 532-nm laser photocoagulator (Topcon Inc., Tokyo, Japan). The laser aiming beam and the OCT scan were aligned to obtain real time tomographic imaging of the irradiated area during laser exposure. Standard and subthreshold laser irradiation and simultaneous OCT acquisition were tested in artificial and biological samples. Laser testing cards were chosen as artificial samples. Freshly enucleated pig eyes were used for iris irradiation. RESULTS: Ophthalmoscopically visible reference burns were placed on the laser testing card in 2 parallel lines. Then, a series of laser spots with the same size and duration but different power were placed between the reference burns. Online OCT during laser irradiation detected changes in the reflectivity profile of the artificial sample at a power of 200 mW, in absence of ophthalmoscopically visible lesions. Similarly, reference burns were placed on pig iris and between them various laser spots were performed at ranging powers. Changes in the iris optical properties, as detected with online OCT, were produced with a power of 860 mW in absence of visible endpoint. CONCLUSIONS: Online OCT is able to identify non-ophthalmoscopically visible lesions during subthreshold laser irradiation either in artificial samples or in pig iris. PMID- 22081665 TI - Do AML patients with DNMT3A exon 23 mutations benefit from idarubicin as compared to daunorubicin? A single center experience. AB - Mutations in DNMT3A encoding DNA methyltransferase 3A were recently described in patients with acute myeloid leukemia. To assess their prognostic significance, we determined the mutational status of DNMT3A exon 23 in 288 patients with AML excluding acute promyelocytic leukemia, aged from 18 to 65 years and treated in Toulouse University Hospital. A mutation was detected in 39 patients (13.5%). All DNMT3A exon 23+ patients had intermediate-risk cytogenetics. Mutations significantly correlated with a higher WBC count (p less than 0.001), NPM1 and FLT3-ITD mutations (p=0.027). DNMT3A mutations were conserved through xenotransplantation in immunodeficient mice. No difference in outcome between DNMT3A exon 23+ and DNMT3A exon 23- patients was found even if the results were stratified by NPM1 or FLT3-ITD status. However, DNMT3A exon 23+ patients had better median DFS (not reached vs 11.6 months, p=0.009) and OS (not reached vs 14.3 months, p=0.005) as compared to DNMT3A exon 23- patients when treated with idarubicin, whereas patients treated with daunorubicin had similar outcome regardless the DNMT3A status. This study shows that DNMT3A mutations have no impact on outcome but could be a predictive factor for response to idarubicin and thus, could have a direct influence in the way AML patients should be managed. PMID- 22081668 TI - Reversal of sensation of conjunctival autograft after pterygium surgery. AB - PURPOSE: To evaluate sensation change at nasal and superior conjunctival and corneal quadrants after pterygium surgery with conjunctival autograft. METHODS: A prospective study was carried out in 14 patients. Seventeen eyes were operated for primary nasal pterygium. Sensation in nasal and superior conjunctival and corneal quadrants was measured with a Cochet-Bonnet aesthesiometer (CBA) before, and at 2 weeks, 1 month, and every month for 6 months after surgery. Preoperative and postoperative measurements were recorded and analyzed with Wilcoxon signed rank test. RESULTS: The mean patient age was 53.5 years (range 44-68). All patients had nasal primary pterygium and completed the 6-month follow-up. The conjunctival autograft was correctly positioned and fixed in all eyes with fibrin glue. Mean +/- SD sensations in conjunctival autograft were none (p<0.05) at 1 month, 4.28 +/- 5.34 mm (p<0.05) at 2 months, 12.85 +/- 2.67 mm (p<0.05) at 3 months, and returned to normal level, 23.57 +/- 2.43 mm (p>0.05), at 4 months. Mean sensations in superior conjunctival area where the autograft was harvested were 11.42 +/- 5.56 mm (p<0.05) at 1 month, and returned to normal level, 22.14 +/- 2.67 mm (p>0.05), at 2 months. Mean sensations in nasal corneal area after surgery were 7.81 +/- 4.06 mm (p<0.05) at 2 weeks, 26.42 +/- 2.43 mm (p<0.05) at 1 month, and returned to normal level, 49.00 +/- 3.38 mm (p>0.05), at 2 months. Mean sensations in superior corneal area did not change postoperatively. CONCLUSIONS: Anesthesia at first month and hypoesthesia at second and third month at conjunctival autograft was observed after pterygium surgery. Additionally, hypoesthesia was observed at nasal cornea and superior bulbar conjunctiva at the first month. PMID- 22081669 TI - Optic disc pit maculopathy: the value of small-gauge vitrectomy, peeling, laser treatment, and gas tamponade. AB - PURPOSE: To report the outcome of 10 patients with optic pit maculopathy (OPM) and evaluate the role of small-gauge vitrectomy, gas endotamponade, and additional laser photocoagulation treatment. METHODS: We retrospectively investigated 10 patients who underwent small-gauge, sutureless vitrectomy for OPM, detachment of the posterior hyaloid, internal limiting membrane (ILM) peeling, endolaser photocoagulation on the temporal margin of the optic disc, and gas tamponade. Preoperative and postoperative best-corrected visual acuity (BCVA) was recorded and optical coherence tomography (OCT) imaging was performed. RESULTS: Seven out of 10 patients gained at least 2 lines of vision; 2 patients gained 1 line of vision. Visual improvement occurred more than 3 months after surgery. One myopic patient developed a macular hole postoperatively, resulting in a poor functional result even though complete retinal attachment was achieved. The functional outcome did not always correlate well with the OCT imaging, in which complete retinal reattachment was observed in 5 out of 10 eyes. CONCLUSIONS: The therapeutic approach should include both small-gauge vitrectomy and ILM peeling to relieve vitreoretinal traction, as well as laser photocoagulation of the temporal margin of the optic disc in order to prevent vitreous fluid from entering the subretinal/intraretinal space. In addition, the patients should be told that visual recovery can take a long time. PMID- 22081670 TI - The effect of intravitreal bevacizumab (Avastin) injection on retinal blood flow velocity in patients with choroidal neovascularization. AB - PURPOSE: To study the short-term effects of intravitreal bevacizumab (Avastin) on retinal blood flow velocity and compare them to clinical outcomes assessed by optical coherence tomography (OCT) and tests of visual acuity. METHODS: The Retinal Function Imager (RFI) was used noninvasively and quantitatively to measure retinal blood flow velocity. Eight patients receiving intravitreal injection of Avastin for choroidal neovascularization (CNV) were included in this study. All were imaged by the RFI preinjection and 1 and 7 days postinjection. Visual acuity (VA) and OCT were recorded preinjection and 1 month postinjection. Comparisons were performed using paired Student t test and correlation using Spearman rank test. RESULTS: A good correlation was found between the 1-month change in VA and OCT measurements and the short-term change induced in blood flow velocity. Arterial and venous velocity changes 1 day after the injection correlated with the VA change (p<0.05). The 1-day arterial velocity changes correlated with total macular volume (p=0.02) and venous velocity changes correlated to central macular thickness (p = 0.04). CONCLUSIONS: The RFI provides a noninvasive technique to assess early hemodynamic responses to intravitreal injection of Avastin. These early changes may prove important for better understanding of the mechanism underlying this treatment and serve as a quantitative marker for treatment optimization. PMID- 22081671 TI - Retrospective study of rhegmatogenous retinal detachments secondary to round retinal holes. AB - PURPOSE: The authors aim to analyze the incidence, characteristics, surgical management, and outcome of patients presenting to St Thomas' Hospital with a rhegmatogenous retinal detachment secondary to atrophic round retinal holes. METHODS: This is a retrospective collation of patients presenting to a single surgeon with a round hole-associated retinal detachment between 2001 and 2009. Specific collation of demographics, retinal detachment features, choice of management, complications, requirement for further surgery, and ultimate surgical success with final visual acuity is reported. RESULTS: Fifty-six patients with a retinal detachment secondary to a round hole were identified (4.49% incidence). The cohort had a median age of 28.9 years (range 14 to 39) and a female predominance (64%). The median spherical equivalent refractive error was -5.5 diopters (range -1 to -18). The commonest quadrant with retinal holes was the inferotemporal quadrant (40% of patients). Approximately half of our cohort were identified to have lattice degeneration at any site and in either eye. The majority of patients received an external nondrainage procedure (92%) with cryotherapy (88%) and an explant (94%). Three patients required further surgery to achieve retinal reattachment and 12% required surgery for a retinal detachment in the fellow eye. At final follow-up, 78% achieved a visual acuity of 0.18 logMAR (6/12 Snellen) or better and the median final visual acuity was 0.00 logMAR (6/6 Snellen). CONCLUSIONS: Retinal detachments secondary to round holes have consistent characteristic features (young, myopic, female, inferior detachment). Surgical management is increasingly advocated and most achieve primary surgical success with a good final visual acuity. PMID- 22081672 TI - Performance of imaging devices versus optic disc and fiber layer photography in a clinical practice guideline for glaucoma diagnosis. AB - PURPOSE: To compare the performance of Moorfields Regression Analysis (MRA) and optical coherence tomography (OCT) with that of photographic evaluation of the optic nerve head and retinal nerve fiber layer (RNFL) in the application of the Finnish Evidence-Based Guideline for Open-Angle Glaucoma (FEBG-OAG). METHODS: Patients referred for glaucoma evaluation (n=312) and subjects selected from the general population (n=41) were included in the study. All subjects underwent ophthalmic evaluation, optic nerve head stereophotography, monochromatic RNFL photography, Heidelberg retina tomography, OCT, and laser polarimetry evaluation. The subjects were classified based on stereophotographic or MRA and OCT results by applying the FEBG-OAG. RESULTS: The specificity of the FEBG-OAG for detecting normal patients (stereophotography and imaging devices) was 78% (strict criteria) and 100% (liberal criteria). Agreement between the stereophotographic evaluation and evaluation based on MRA and OCT was 70.2%. Classification of subjects with similar management advice based on these evaluations had 70.5% agreement. Central corneal thickness was a confounding factor in glaucoma diagnosis. Large optic disc sizes played a major role in misleading the diagnosis compared to small discs. CONCLUSIONS: Central corneal thickness and large optic disc size are confounding factors in glaucoma diagnosis. Moorfields Regression Analysis and OCT allow for objective implementation of the FEBG-OAG compared to conventional stereophotographic evaluation of the neuroretinal structures. PMID- 22081673 TI - Overcoming the clinical-MR imaging paradox of multiple sclerosis: MR imaging data assessed with a random forest approach. AB - BACKGROUND AND PURPOSE: In MS, the relation between clinical and MR imaging measures is still suboptimal. We assessed the correlation of disability and specific impairment of the clinical functional system with overall and regional CNS damage in a large cohort of patients with MS with different clinical phenotypes by using a random forest approach. MATERIALS AND METHODS: Brain conventional MR imaging and DTI were performed in 172 patients with MS and 46 controls. Cervical cord MR imaging was performed in a subgroup of subjects. To evaluate whether MR imaging measures were able to correctly classify impairment in specific clinical domains, we performed a random forest analysis. RESULTS: Between-group differences were found for most of the MR imaging variables, which correlated significantly with clinical measures (r ranging from -0.57 to 0.55). The random forest analysis showed a high performance in identifying impaired versus unimpaired patients, with a global error between 7% (pyramidal functional system) and 31% (Ambulation Index) in the different outcomes considered. When considering the performance in the unimpaired and impaired groups, the random forest analysis showed a high performance in identifying patients with impaired sensory, cerebellar, and brain stem functions (error below 10%), while it performed poorly in defining impairment of visual and mental systems (error of 91% and 70%, respectively). In analyses with a good level of classification, for most functional systems, damage of the WM fiber bundles subserving their function, measured by using DTI tractography, had the highest classification power. CONCLUSIONS: Random forest analysis, especially if applied to DTI tractography data, is a valuable approach, which might contribute to overcoming the MS clinical-MR imaging paradox. PMID- 22081674 TI - Pediatric intracranial aneurysms: new and enlarging aneurysms after index aneurysm treatment or observation. AB - BACKGROUND AND PURPOSE: Children with brain aneurysms may be at higher risk than adults to develop new or enlarging aneurysms in a relatively short time. We sought to identify comorbidities and angiographic features in children that predict new aneurysm formation or enlargement of untreated aneurysms. MATERIALS AND METHODS: Retrospective analysis of the University of California-San Francisco Pediatric Aneurysm Cohort data base including medical records and imaging studies was performed. RESULTS: Of 83 patients harboring 114 intracranial aneurysms not associated with brain arteriovenous malformations or intracranial arteriovenous fistulas, 9 (8.4%) developed new or enlarging brain aneurysms an average of 4.2 years after initial presentation. Comorbidities that may be related to aneurysm formation were significantly higher in patients who developed new aneurysms (89%) as opposed to patients who did not develop new or enlarging aneurysms (41%; RR, 9.5; 95% CI, 1.9%-48%; P = .0099). Patients with multiple aneurysms at initial presentation were more likely than patients with a single aneurysm at presentation to develop a new or enlarging aneurysm (RR, 6.2; 95% CI, 2.1%-185; P = .0058). Patients who initially presented with at least 1 fusiform aneurysm were more likely to develop a new or enlarging aneurysm than patients who did not present with a fusiform aneurysm (RR, 22; 95% CI, 3.6%-68%; P = .00050). Index aneurysm treatment with parent artery occlusion also was associated with higher risk of new aneurysm formation (RR, 4.2; 95% CI, 1.3%-13%; P = .024). New aneurysms did not necessarily arise near index aneurysms. The only fatality in the series was due to subarachnoid hemorrhage from a new posterior circulation aneurysm arising 20 months after index anterior circulation aneurysm treatment in an immunosuppressed patient. CONCLUSIONS: Patients who presented with a fusiform aneurysm had a significantly greater incidence of developing a new aneurysm or enlargement of an index aneurysm than did those who presented with a saccular aneurysm. In our patient cohort, 8 of the 9 children who eventually developed new or enlarging brain aneurysms initially presented with fusiform aneurysm morphology. Other comorbidities or multiple aneurysms were also common in these patients at initial presentation. PMID- 22081675 TI - Structural brain abnormalities in patients with Parkinson disease: a comparative voxel-based analysis using T1-weighted MR imaging and magnetization transfer imaging. AB - BACKGROUND AND PURPOSE: In PD, tissue damage occurs in specific cortical and subcortical regions. Conventional MR images have only limited capacity to depict these structural changes. The purpose of the current study was to investigate whether voxel-based MT imaging could indicate structural abnormalities beyond atrophy measurable with T1-weighted MR imaging. MATERIALS AND METHODS: Thirty-six patients with PD without dementia (9 in H&Y stage 1, thirteen in H&Y 2, eleven in H&Y 3, three in H&Y 4) and 23 age-matched control subjects were studied with T1 weighted MR imaging and MT imaging. Voxel-based analyses of T1-weighted MR imaging was performed to investigate brain atrophy, while MT imaging was used to study abnormalities within existing tissue. Modulated GM and WM probability maps, sensitive to volume, and nonmodulated maps, indicative of tissue density, were obtained from T1-weighted MR imaging. Effects seen on MTR images, but absent on density maps, were attributed to damage of existing tissue. RESULTS: Contrary to T1-weighted MR imaging, MT imaging was sensitive to the progression of brain pathology of the neocortex and paraventricular WM. MTR images and T1-based volume images, but not density images, showed a progression of disease in the olfactory cortex, indicating the occurrence of atrophy as well as damage to existing tissue in this region. MTR images revealed bilateral damage to the SN, while T1-weighted MR imaging only showed left-sided abnormalities. CONCLUSIONS: The findings suggest that voxel-based MT imaging permits a whole-brain unbiased investigation of CNS structural integrity in PD and may be a valuable tool for identifying structural damage occurring without or before measurable atrophy. PMID- 22081676 TI - Strong magnets. PMID- 22081677 TI - Cerebral perfusion long term after therapeutic occlusion of the internal carotid artery in patients who tolerated angiographic balloon test occlusion. AB - BACKGROUND AND PURPOSE: Therapeutic carotid occlusion is an established technique for treatment of large and giant aneurysms of the ICA, in patients with synchronous venous filling on angiography during BTO. Concern remains that hemodynamic alterations after permanent occlusion will predispose the patient to new ischemic injury in the ipsilateral hemisphere. The purpose of this study was to assess whether BTO with synchronous venous filling is associated with normal CBF long term after carotid sacrifice. MATERIALS AND METHODS: Eleven patients were included (all women; mean age, 50.5 years; mean follow-up, 38.5 months). ASL with single and multiple TIs was used to assess CBF and its temporal characteristics. Selective ASL was used to assess actual territorial contribution of the ICA and BA. Collateral flow via the AcomA or PcomA or both was determined by time-resolved 3D PCMR. Paired t tests were used to compare CBF and timing parameters between hemispheres. RESULTS: Absolute CBF values were within the normal range. There was no significant CBF difference between hemispheres ipsilateral and contralateral to carotid sacrifice (49.4 +/- 11.2 versus 50.1 +/- 10.1 mL/100 g/min). Arterial arrival time and trailing edge time were significantly prolonged on the occlusion side (816 +/- 119 ms versus 741 +/- 103 ms, P = .001; and 1765 +/- 179 ms versus 1646 +/- 190 ms, P < .001). Two patients had collateral flow through the AcomA only and were found to have increased timing parameters compared with 9 patients with mixed collateral flow through both the AcomA and PcomA. CONCLUSIONS: In this small study, patients with synchronous venous filling during BTO had normal CBF long term after therapeutic ICA occlusion. PMID- 22081678 TI - Porcine brachial artery tortuosity for in vivo evaluation of neuroendovascular devices. AB - We report a novel model of arterial tortuosity in the porcine brachial artery for testing of endovascular devices in the flexed forelimb position. This provides an ideal vascular territory for an in vivo assessment of guidewires, microcatheters, and endovascular implants because it closely mimics the challenging curvature at the carotid siphon. PMID- 22081679 TI - Different patterns of fornix damage in idiopathic normal pressure hydrocephalus and Alzheimer disease. AB - BACKGROUND AND PURPOSE: The fornix contains efferent fibers of the hippocampus and is in close contact with the corpus callosum. Part of the fornix is directly attached to the corpus callosum, and another part is suspended from the corpus callosum via the septum pellucidum. DTI can be used to evaluate the morphology and microstructural integrity of the fornix. We examined the pattern of fornix damage in patients with iNPH or AD. MATERIALS AND METHODS: We enrolled 22 patients with iNPH, 20 with AD, and 20 healthy controls. DTI data were obtained. The morphology (volume, length, and mean cross-sectional area) and FA values of the fornix were evaluated by using tract-specific analysis and compared among groups. RESULTS: The volume, cross-sectional area, and FA value of the fornix were significantly smaller in patients with iNPH than in controls, whereas the length was significantly greater. In patients with AD, the volume, mean cross sectional area, and FA value of the fornix were significantly smaller than those in controls, whereas the length was not altered. The fornix was significantly longer in patients with iNPH than in patients with AD, whereas the volume and cross-sectional areas were significantly smaller. CONCLUSIONS: Our results suggest that the different pathogeneses of these diseases lead to fornix damage through different mechanisms: through mechanical stretching due to lateral ventricular enlargement and corpus callosum deformation in patients with iNPH, and through degeneration secondary to hippocampal atrophy in patients with AD. PMID- 22081680 TI - The effect of age and cerebral ischemia on diffusion-weighted proton MR spectroscopy of the human brain. AB - BACKGROUND AND PURPOSE: DW-MRS is a promising tool for the noninvasive identification of the cellular response to cerebral ischemia. To date, the potential confounding effects of aging and the stage of ischemia are unknown. We, therefore, examined the cross-sectional effects of age and different stages of cerebral ischemia on the diffusion of brain metabolites. MATERIALS AND METHODS: The ADCs of 3 major metabolites, including Cho, Cr, and NAA were measured by DW MRS in healthy younger (n = 26, 24 +/- 2.2 years of age) and older (n = 17, 63 +/ 7.0 years of age) adults, as well as in patients with acute (n = 7, 57 +/- 4.0 years of age) and subacute (n = 12, 62 +/- 7.8 years of age) cerebral ischemia. RESULTS: Compared with younger adults, healthy older adults presented with significantly reduced ADC values of NAA (P = .000052), Cr (P = .000018), and Cho (P = .00075). Meanwhile, the ADC values of NAA (F(2,36) = 6.057, P = .006), Cr (F(2,36) = 5.634, P = .008), and Cho (F(2,36) = 8.167, P = .001) were significantly different among the acute cerebral ischemia group, subacute cerebral ischemia group, and healthy older controls. These metabolites decreased in the acute stage of cerebral ischemia but increased in the subacute stage, compared with age-matched controls. CONCLUSIONS: The effect of age should be considered when analyzing diffusion of cerebral metabolites with DW-MRS. Our observations also suggest that metabolite diffusion data may be used to reveal changes in the intracellular environment, depending on the pathologic status of ischemia. PMID- 22081681 TI - Daydreaming about our metaphorical tool belt. PMID- 22081682 TI - Carotid artery wall thickness measured using CT: inter- and intraobserver agreement analysis. AB - SUMMARY: The purpose of this work was to compare inter- and intraobserver agreement in the analysis of CAWT by using MDCTA. The CAWT in 35 patients was quantified by 4 observers. Bland-Altman statistics were used to measure the agreement between observers. The results of our study demonstrated that the CAWT measured by using MDCTA shows a good reproducibility between observers by considering inter- and intraobserver agreement. PMID- 22081683 TI - Pituitary iron and volume imaging in healthy controls. AB - BACKGROUND AND PURPOSE: Patients with transfusional iron overload develop iron deposits in the pituitary gland, which are associated with volume loss and HH. The purpose of this study was to characterize R2 and volumetric data in a healthy population for diagnostic use in patients with transfusional iron overload. MATERIALS AND METHODS: One hundred healthy controls without iron overload between the ages of 2 and 48 were recruited to have MR imaging of the brain to assess their pituitary R2 and volume. Pituitary R2 was assessed with a 8-echo spin-echo sequence, and pituitary volumes, by a 3D spoiled gradient-echo sequence with 1 mm(3) resolution. A 2-component continuous piecewise linear approximation was used for creating volumetric and R2 nomograms. Equations were generated from regression relationships for convenient z-score calculation. RESULTS: Pituitary R2 rose weakly with age (r(2) = 0.19, P < .0001). Anterior and total pituitary volumes increased steadily up to 18 years of age, after which volume slightly decreased. Females had larger pituitary glands, most likely representing their larger lactotroph population. CONCLUSIONS: From these data, a clinician can calculate the z scores for R2 and pituitary volume in patients with iron overload. Normal ranges are well-differentiated from values previously associated with endocrine disease in transfusional siderosis; this finding suggests that preclinical iron overload can be recognized and appropriately treated. PMID- 22081684 TI - Dairy micronutrients: new insights and health benefits. Introduction. PMID- 22081685 TI - Milk and dairy products: a unique micronutrient combination. AB - Milk and dairy products contain micronutrients such as minerals and vitamins, which contribute to multiple and different vital functions in the organism. The mineral fraction is composed of macroelements (Ca, Mg, Na, K, P, and Cl) and oligoelements (Fe, Cu, Zn, and Se). From a physicochemical point of view, the chemical forms, the associations with other ions or organic molecules, and the location of macroelements such as Ca, Mg, Na, K, P, and Cl in milk are relatively well described and understood. Thus, it is admitted that these macroelements are differently distributed into aqueous and micellar phases of milk, depending on their nature. K, Na, and Cl ions are essentially in the aqueous phase, whereas Ca, P, and Mg are partly bound to the casein micelles. About one third of the Ca, half of the P, and two thirds of the Mg are located in the aqueous phase of milk. Dairy products are more or less rich in these different minerals. In cheeses, mineral content depends mainly on their processing. The Ca content is strongly related to the acidification step. Moreover, if acidification is associated with the draining step, the Ca content in the cheese will be reduced. Thus, the Ca content varies in the following increasing order: milks/fermented milks/fresh cheeses < soft cheeses < semi-hard cheeses < hard cheeses. The chemical forms and associations are less described than those present in milk. Concerning Ca, the formation of insoluble calcium phosphate, carbonate, and lactate is reported in some ripened cheeses. The NaCl content in cheeses depends on the salting of the curd. From a nutritional point of view, it is largely admitted that milk and dairy products are important sources of Ca, Mg, Zn, and Se. The vitamin fraction of milk and dairy products is composed of lipophilic (A, D, E, and K) and hydrophilic (B(1), B(2), B(3), B(5), B(6), B(8), B(9), B(12), and C) vitamins. Because of their hydrophobic properties, the lipophilic vitamins are mainly in the milk fat fraction (cream, butter). The hydrophilic vitamins are in the aqueous phase of milk. For one part of these vitamins, the concentrations described in the literature are not always homogenous and sometimes not in accordance between them; these discrepancies are due to the difficulty of the sample preparation and the use of appropriate methods for their quantification. However, there is no doubt of the significant contribution of milk and dairy products to the intake of vitamins. Milk and dairy are considered essential sources for vitamins. Key teaching points: Milk and dairy products are unique micronutrient combinations with recognized health benefits. The concentration, chemical forms, and location of different minerals are relatively well known and described. For example, Ca is present in dairy products in different forms: free, associated with citrate, inorganic and organic phosphates, and free fatty acids. Milk and dairy products are excellent sources of Ca, P, Mg, Zn, and Se. The concentration of vitamins in milk and dairy products is variable and depends on several factors such as biosynthesis, animal feeding, physicochemical conditions (heat, light, O(2), oxidant agents), and analytical methods for their determinations. Vitamins A, D, E, and K are mainly located in the lipid phase and vitamins of group B and C in the aqueous phase. Milk and dairy products are excellent sources of vitamins A, B(1), B(2), and B(12). PMID- 22081686 TI - The contribution of dairy products to micronutrient intakes in France. AB - OBJECTIVE: To assess the contribution of milk and dairy products to the intake of vitamins and minerals in the French population. METHODS: Data from the French Individual National Food Consumption Survey 2 (2005-2007) carried out in a representative sample of French people aged 3 to 79 years were used for analysis. RESULTS: Dairy products are strong contributors of calcium; iodine; phosphorus; potassium; zinc; vitamins B(2), B(12), B(5), and D; and retinol. Of all dairy products, milk contributes the most to the intake of these nutrients in children, whereas in adults, cheese and ultra-fresh dairy products contribute equally. CONCLUSION: Dairy products are an important source of vitamins and minerals in the French population and help strongly to meet micronutrient recommendations for both children and adults. PMID- 22081687 TI - The contribution of dairy products to micronutrient intake in the Netherlands. AB - OBJECTIVE: To assess the contribution of dairy products to the intake of various vitamins and minerals in several life stages in the Dutch population. METHOD: Data from 3 Dutch Food Consumption Surveys and the Leiden Longevity Study were used to estimate the contribution of dairy products--as percentage of total intake--to the intake of iron, copper, selenium, zinc, calcium, folic acid, vitamin D, vitamin C, and vitamin B(12). RESULTS: In young children, dairy products contributed substantially to the intake of calcium (73%), selenium (21%), iron (8%), zinc (39%), copper (12%), folic acid (24%), vitamin C (18%), vitamin D (16%), and vitamin B(12) (58%). Of all dairy products, milk contributed the most to the intake of these nutrients. In adults and elderly subjects, the contribution of dairy products to total micronutrient intake was 65%-68% for calcium, 18%-19% for selenium, 3%-4% for iron, 28%-31% for zinc, 6%-7% for copper, 17%-19% for folic acid, 10%-14% for vitamin C, 11%-16% for vitamin D, and 44%-46% for vitamin B(12). Milk as well as cheese contributed the most to the intake of these nutrients. CONCLUSIONS: Dairy products are an important source of vitamins and minerals in the Dutch population. Dairy products, especially milk and cheese, contribute substantially to the intake of calcium, selenium, zinc, and vitamin B(12). PMID- 22081688 TI - The contribution of milk and milk products to micronutrient density and affordability of the U.S. diet. AB - BACKGROUND: To be successful, dietary guidance needs to identify foods that are nutrient rich, affordable, and appealing. Analyses of dietary surveys on "what we eat in America" can now be supplemented by analyses of nutrient density as well as nutrient cost. OBJECTIVE: To explore the relative contribution of 9 food groups to energy and nutrient intakes and to assess the relative cost of selected nutrients by major food group. METHOD: Dietary intake data were provided by the 4 cycles of the continuous National Health and Nutrition Examination Survey (NHANES 2001-2002, 2003-2004, 2005-2006, and 2007-2008). Research on the nutritive value and cost of U.S. foods was made possible by the merging of the U.S. Department of Agriculture (USDA) Food and Nutrition Database for Dietary Studies (FNDDS 2.0) with the USDA food prices database. Nutrient densities were calculated per 100 kcal. Nutrient costs were calculated as the dollar cost of meeting 10% daily value for a given nutrient. RESULTS: Despite their low energy contribution (10% 13% of energy), milk and milk products contributed 47% of calcium, 42% of retinol, and 65% of vitamin D to the diets of children and adults. Milk and milk products were among the top sources of riboflavin, phosphorous, and vitamin B(12). Cost analyses showed that milk and milk products were by far the lowest cost source of dietary calcium and were among the lowest-cost sources of riboflavin and vitamin B(12). Vegetables and fruit were the lowest-cost sources of vitamin C, whereas dry beans and legumes were the lowest-cost sources of fiber. CONCLUSION: The nutrients-per-calorie and nutrient cost metrics can help identify affordable nutrient-rich foods. PMID- 22081689 TI - Evidence-based dietary guidance and the role of dairy products for appropriate nutrition in the elderly. AB - Food consumption surveys in the elderly come to the general conclusions that most elderly people outside institutions eat reasonably well. There is, however, tremendous variation in health status between older adults. The aging process is complex and influenced not only by factors intrinsic to the individual but also by extrinsic factors. The latter includes nutrition. In the various phases in the aging process, nutritional status and thus appropriate nutrition differ. Undernutrition is a great concern. In community-dwelling people older than 70 years, 5%-10% are undernourished, and for institutionalized elderly, this is up to 30%-65%. The cause is often inappropriate food consumption, and treatment is not always evidence based. National evidence-based dietary guidelines are mainly for healthy elderly people and vary between regions and even between institutes within the same region. To understand these differences, insight is required into the paradigm applied for nutritional science and the designs, selection of the older population, methodology, and endpoints of studies supplying the science behind the guidelines. A European project (Eurecca) compiles and harmonizes dietary guidelines. These activities underpin the need for sound evidence to improve the nutrition of older adults in different health phases. For frail elderly, there is also a plea to take into account results of studies on food satisfaction. First studies in this field show the effectiveness of an adapted social context for meals, appropriate nutritional care, and availability of tasty drinks and foods for selected groups of older adults. Because of the nutrient richness of dairy products and their good taste, these foods are helpful in the diet of healthy as well as frail elderly people. Key teaching points: Most elderly people eat reasonably well. There are, however, large differences in health status between elderly people and therefore also in nutrient requirements. Undernutrition is a main concern. In community-dwelling people older than 70 years, 5%-10% are undernourished, and for institutionalized elderly, this is up to 30%-65%. Evidence-based dietary guidelines are developed mainly for healthy elderly people and vary between regions. Harmonization will improve public health as well as clinical nutritional strategies. Given the nutrient density of dairy products, these products are included in balanced dietary advice for older adults. PMID- 22081690 TI - Calcium and phosphate: a duet of ions playing for bone health. AB - The acquisition and maintenance of bone mass and strength are influenced by environmental factors, including physical activity and nutrition. Among micronutrients, calcium (Ca) and inorganic (i) phosphate (P) are the two main constituents of hydroxyapatite, the bone mineral that strengthens the mechanical resistance of the organic matrix. Bone contains about 99% and 80% of the body's entire supply of Ca and P, respectively. The Ca/P mass ratio in bone is 2.2, which is similar to that measured in human milk. The initial step of Ca-Pi crystal nucleation takes place within matrix vesicles that bud from the plasma membrane of osteogenic cells and migrate into the extracellular skeletal compartment. They are endowed with a transport system that accumulates Pi inside the matrix vesicles, followed by the influx of Ca ions. This process leads to the formation of hydroxyapatite crystal and its subsequent association with the organic matrix collagen fibrils. In addition to this structural role, both Ca and Pi positively influence the activity of bone-forming and bone-resorbing cells. Pi plays a role in the maturation of osteocytes, the most abundant cells in bone. Osteocytes are implicated in bone mineralization and systemic Pi homeostasis. They produce fibroblast growth factor-23, a hormonal regulator of renal Pi reabsorption and 1,25-dihydroxy vitamin D production. This relationship is in keeping with the concept proposed several decades ago of a bone-kidney link in Pi homeostasis. In contrast to their tight association in bone formation and resorption, Ca and Pi renal reabsorption processes are independent from each other, driven by distinct molecular machineries. The distinct renal control is related to the different extraskeletal functions that Ca and Pi play in cellular metabolism. At both the renal and the intestinal levels, interactions of Ca and Pi have been documented that have important implications in the acquisition and maintenance of bone health, as well as in osteoporosis management. In the kidney, increased Pi intake enhances Ca reabsorption and Ca balance. During growth and adulthood, administration of Ca-Pi in a ratio close to that of dairy products leads to positive effects on bone health. In contrast, when separately ingested as pharmaceutical salt supplements, thus inducing large differences between Ca and Pi concentrations in the intestinal lumen, they might have adverse effects on bone health. In osteoporotic patients treated with anabolic agents, a Ca-Pi supplement appears to be preferable to carbonate or citrate Ca salt. In conclusion, Ca and Pi constitute a key duo for appropriate bone mineral acquisition and maintenance throughout life. Outside the skeleton, their essential but distinct physiological functions are controlled by specific transporters and hormonal systems that also serve to secure the appropriate supply of Ca and Pi for bone health. Key teaching points: Bone contains about 99% and 80% of the body's supply of Ca and P, respectively, as hydroxyapatite and has a Ca/P mass ratio of about 2.2, close to that measured in human milk. The first step of Ca-Pi crystal nucleation takes place within matrix vesicles that bud from the plasma membrane of osteogenic cells. In addition to their structural role, both Ca and Pi influence bone-forming and bone-resorbing cells. There is a bone kidney link in Pi homeostasis in which fibroblast growth factor-23, a molecule produced by osteocytes, appears to play a pivotal role. In contrast to their tight association during bone formation and resorption, both intestinal and renal Ca and Pi processes are independent of each other. Observational and interventional studies suggest that Ca-Pi salt or dairy products can exert positive effects on bone acquisition and maintenance. PMID- 22081691 TI - Human obesity: is insufficient calcium/dairy intake part of the problem? AB - Epidemiological data have shown that low calcium intake is a risk factor for overweight and obesity. The clinical implications of this relationship have been confirmed in weight loss studies performed in low calcium consumers in whom calcium or dairy supplementation accentuated body weight and fat loss. Up to now, laboratory studies and clinical trials have demonstrated that this effect may be explained by an increase in fat oxidation and fecal loss as well as a facilitation of appetite control. Taken together, these observations suggest that insufficient calcium intake can be part of the obesity problem in some individuals and that an increase in calcium/dairy intake is part of the solution. Key teaching points: Low dietary calcium intake is a significant risk factor for overweight in adults. Calcium/dairy supplementation may accentuate the impact of a weight-reducing program in obese low calcium consumers. Calcium/dairy supplementation promotes fecal fat loss and fat oxidation. Calcium/dairy supplementation favors a decrease in energy intake and a facilitation of appetite control in obese individuals during weight loss. PMID- 22081692 TI - Dairy products and the metabolic syndrome in a prospective study, DESIR. AB - OBJECTIVE: In previous cross-sectional analyses of the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, we have found inverse associations between dairy product consumption and metabolic syndrome (MetS) traits. We have now analyzed in a prospective way the influence of dairy product and calcium consumption at inclusion on the 9-year cumulative incidence of the MetS and associated traits in the French prospective study with a 9-year follow-up, DESIR. METHODS: After exclusion of diabetic subjects and those being on a diet at inclusion, 3417 men and women who completed a food frequency at baseline could be studied. Logistic regression models were used to study associations between dairy products and dietary calcium density at baseline and incident MetS and impaired fasting glycemia/type 2 diabetes (IFG/T2D) after adjusting for gender, age, and lifestyle parameters (alcohol, smoking, physical activity, fat intake). An additional model adjusting for the same covariates and for body mass index (BMI) was also used. Associations between dairy products and continuous variables were studied by repeated measures analysis of covariance, using the same covariates. RESULTS: Total dairy product consumption, dairy (except cheese) consumption, and dietary calcium density were inversely associated with incident MetS and IFG/T2D. Cheese consumption was negatively associated with incident MetS but not with glycemic disorders. All parameters were associated with lower diastolic blood pressure and triglycerides (average over the 9-year period) and with a lower BMI gain in the same period. Higher total dairy and cheese intake and calcium density were associated with a lower increase in waist circumference and triglycerides during the 9-year follow-up. CONCLUSION: In the French general population, these results show beneficial effects of dairy product consumption on the metabolic syndrome and glycemic disorders. Therefore, dairy product consumption could be protective against cardiovascular risk. PMID- 22081693 TI - Dairy products and cancer. AB - Cancer is a group of more than 100 diseases in which cells display uncontrolled growth, invasion, and sometimes metastasis. Milk and dairy products contain micronutrients and several bioactive constituents that may influence cancer risk and progression. Much of the focus of human, population-based studies has been on the effects of intake of milk and total dairy products or of calcium intake. Based on a systematic review of the epidemiologic literature, the World Cancer Research Fund and American Institute for Cancer Research report concluded there was a probable association between milk intake and lower risk of colorectal cancer, a probable association between diets high in calcium and increased risk of prostate cancer, and limited evidence of an association between milk intake and lower risk of bladder cancer. For other cancers, the evidence was mixed or lacking. Since the 2007 report, several additional, large-cohort studies have been published, including two that show an inverse association between intake of cultured dairy products and bladder cancer. Little is known about the potential effect of various bioactives produced during rumen microbe metabolism on cancer risk. Furthermore, studies support a role of live microbes present in some dairy products in the modulation of the human gut microbial community and gut metabolism. Given the growing appreciation for the role of the gut microbial community in relation to immune function and health and disease, including cancer, the potential role of various dairy products in the modulation of the human gut microbiome warrants further evaluation. Key teaching points: As a dietary exposure, dairy products are a complex group of foods and composition varies by region, which makes evaluation of their association with disease risk difficult. For most cancers, associations between cancer risk and intake of milk and dairy products have been examined only in a small number of cohort studies, and data are inconsistent or lacking. Meta-analyses of cohort data available to date support an inverse association between milk intake and risk of colorectal and bladder cancer and a positive association between diets high in calcium and risk of prostate cancer. Other constituents of dairy products, such as rumen derived metabolites, have not been evaluated extensively for cancer-preventive properties. The influence of live microbes in fermented dairy products and certain cheeses on the human gut microbiome and immune function is a growing area of study. PMID- 22081694 TI - Milk and acid-base balance: proposed hypothesis versus scientific evidence. AB - Recently the lay press has claimed a hypothetical association among dairy product consumption, generation of dietary acid, and harm to human health. This theoretical association is based on the idea that the protein and phosphate in milk and dairy products make them acid-producing foods, which cause our bodies to become acidified, promoting diseases of modern civilization. Some authors have suggested that dairy products are not helpful and perhaps detrimental to bone health because higher osteoporotic fracture incidence is observed in countries with higher dairy product consumption. However, scientific evidence does not support any of these claims. Milk and dairy products neither produce acid upon metabolism nor cause metabolic acidosis, and systemic pH is not influenced by diet. Observations of higher dairy product intake in countries with prevalent osteoporosis do not hold when urban environments are compared, likely due to physical labor in rural locations. Milk and other dairy products continue to be a good source of dietary protein and other nutrients. Key teaching points: Measurement of an acidic pH urine does not reflect metabolic acidosis or an adverse health condition. The modern diet, and dairy product consumption, does not make the body acidic. Alkaline diets alter urine pH but do not change systemic pH. Net acid excretion is not an important influence of calcium metabolism. Milk is not acid producing. Dietary phosphate does not have a negative impact on calcium metabolism, which is contrary to the acid-ash hypothesis. PMID- 22081696 TI - The relative value of strain and strain rate for defining intrinsic myocardial function. AB - It is well accepted that strain and strain rate deformation parameters are not only a measure of intrinsic myocardial contractility but are also influenced by changes in cardiac load and structure. To date, no information is available on the relative importance of these confounders. This study was designed to investigate how strain and strain rate, measured by Doppler echocardiography, relate to the individual factors that determine cardiac performance. Echocardiographic and conductance measurements were simultaneously performed in mice in which individual determinants of cardiac performance were mechanically and/or pharmacologically modulated. A multivariable analysis was performed with radial and circumferential strains and peak systolic radial and circumferential strain rates as dependent parameters and preload recruitable stroke work (PRSW), arterial elastance (E(a)), end-diastolic pressure, and left ventricular myocardial volume (LVMV) as independent factors representing myocardial contractility, afterload, preload, and myocardial volume, respectively. Radial strain was most influenced by E(a) (beta = -0.58, R(2) = 0.34), whereas circumferential strain was strongly associated with E(a) and moderately with LVMV (beta = 0.79 and -0.52, respectively, R(2) = 0.54). Radial strain rate was related to both PRSW and LVMV (beta = 0.79 and -0.62, respectively, R(2) = 0.50), whereas circumferential strain rate showed a prominent correlation only with PRSW (beta = -0.61, R(2) = 0.51). In conclusion, strain (both radial and circumferential) is not a good surrogate measure of intrinsic myocardial contractility unless the strong confounding influence of afterload is considered. Strain rate is a more robust measure of contractility that is less influenced by changes in cardiac load and structure. Thus, peak systolic strain rate is the more relevant parameter to assess myocardial contractile function noninvasively. PMID- 22081698 TI - Endothelial dysfunction as a cellular mechanism for vascular failure. AB - The regulation of vascular tone, vascular permeability, and thromboresistance is essential to maintain blood circulation and therefore tissue environments under physiological conditions. Atherogenic stimuli, including diabetes, dyslipidemia, and oxidative stress, induce vascular dysfunction, leading to atherosclerosis, which is a key pathological basis for cardiovascular diseases such as ischemic heart disease and stroke. We have proposed a novel concept termed "vascular failure" to comprehensively recognize the vascular dysfunction that contributes to the development of cardiovascular diseases. Vascular endothelial cells form the vascular endothelium as a monolayer that covers the vascular lumen and serves as an interface between circulating blood and immune cells. Endothelial cells regulate vascular function in collaboration with smooth muscle cells. Endothelial dysfunction under pathophysiological conditions contributes to the development of vascular dysfunction. Here, we address the barrier function and microtubule function of endothelial cells. Endothelial barrier function, mediated by cell-to cell junctions between endothelial cells, is regulated by small GTPases and kinases. Microtubule function, regulated by the acetylation of tubulin, a component of the microtubules, is a target of atherogenic stimuli. The elucidation of the molecular mechanisms of endothelial dysfunction as a cellular mechanism for vascular failure could provide novel therapeutic targets of cardiovascular diseases. PMID- 22081697 TI - Mathematical modeling mechanisms of arrhythmias in transgenic mouse heart overexpressing TNF-alpha. AB - Transgenic mice overexpressing tumor necrosis factor-alpha (TNF-alpha mice) possess many of the features of human heart failure, such as dilated cardiomyopathy, impaired Ca(2+) handling, arrhythmias, and decreased survival. Although TNF-alpha mice have been studied extensively with a number of experimental methods, the mechanisms of heart failure are not completely understood. We created a mathematical model that reproduced experimentally observed changes in the action potential (AP) and Ca(2+) handling of isolated TNF alpha mice ventricular myocytes. To study the contribution of the differences in ion currents, AP, Ca(2+) handling, and intercellular coupling to the development of arrhythmias in TNF-alpha mice, we further created several multicellular model tissues with combinations of wild-type (WT)/reduced gap junction conductance, WT/prolonged AP, and WT/decreased Na(+) current (I(Na)) amplitude. All model tissues were examined for susceptibility to Ca(2+) alternans, AP propagation block, and reentry. Our modeling results demonstrated that, similar to experimental data in TNF-alpha mice, Ca(2+) alternans in TNF-alpha tissues developed at longer basic cycle lengths. The greater susceptibility to Ca(2+) alternans was attributed to the prolonged AP, resulting in larger inactivation of I(Na), and to the decreased SR Ca(2+) uptake and corresponding smaller SR Ca(2+) load. Simulations demonstrated that AP prolongation induces an increased susceptibility to AP propagation block. Programmed stimulation of the model tissues with a premature impulse showed that reduced gap junction conduction increased the vulnerable window for initiation reentry, supporting the idea that reduced intercellular coupling is the major factor for reentrant arrhythmias in TNF-alpha mice. PMID- 22081699 TI - Constitutive overexpression of phosphomimetic phospholemman S68E mutant results in arrhythmias, early mortality, and heart failure: potential involvement of Na+/Ca2+ exchanger. AB - Expression and activity of cardiac Na(+)/Ca(2+) exchanger (NCX1) are altered in many disease states. We engineered mice in which the phosphomimetic phospholemman S68E mutant (inhibits NCX1 but not Na(+)-K(+)-ATPase) was constitutively overexpressed in a cardiac-specific manner (conS68E). At 4-6 wk, conS68E mice exhibited severe bradycardia, ventricular arrhythmias, increased left ventricular (LV) mass, decreased cardiac output (CO), and ~50% mortality compared with wild type (WT) littermates. Protein levels of NCX1, calsequestrin, ryanodine receptor, and alpha(1)- and alpha(2)-subunits of Na(+)-K(+)-ATPase were similar, but sarco(endo)plasmic reticulum Ca(2+)-ATPase was lower, whereas L-type Ca(2+) channels were higher in conS68E hearts. Resting membrane potential and action potential amplitude were similar, but action potential duration was dramatically prolonged in conS68E myocytes. Diastolic intracellular Ca(2+) ([Ca(2+)](i)) was higher, [Ca(2+)](i) transient and maximal contraction amplitudes were lower, and half-time of [Ca(2+)](i) transient decline was longer in conS68E myocytes. Intracellular Na(+) reached maximum within 3 min after isoproterenol addition, followed by decline in WT but not in conS68E myocytes. Na(+)/Ca(2+) exchange, L type Ca(2+), Na(+)-K(+)-ATPase, and depolarization-activated K(+) currents were decreased in conS68E myocytes. At 22 wk, bradycardia and increased LV mass persisted in conS68E survivors. Despite comparable baseline CO, conS68E survivors at 22 wk exhibited decreased chronotropic, inotropic, and lusitropic responses to isoproterenol. We conclude that constitutive overexpression of S68E mutant was detrimental, both in terms of depressed cardiac function and increased arrhythmogenesis. PMID- 22081700 TI - Cell-to-cell coupling in engineered pairs of rat ventricular cardiomyocytes: relation between Cx43 immunofluorescence and intercellular electrical conductance. AB - Gap junctions are composed of connexin (Cx) proteins, which mediate intercellular communication. Cx43 is the dominant Cx in ventricular myocardium, and Cx45 is present in trace amounts. Cx43 immunosignal has been associated with cell-to-cell coupling and electrical propagation, but no studies have directly correlated Cx43 immunosignal to electrical cell-to-cell conductance, g(j), in ventricular cardiomyocyte pairs. To assess the correlation between Cx43 immunosignal and g(j), we developed a method to determine both parameters from the same cell pair. Neonatal rat ventricular cardiomyocytes were seeded on micropatterned islands of fibronectin. This allowed formation of cell pairs with reproducible shapes and facilitated tracking of cell pair locations. Moreover, cell spreading was limited by the fibronectin pattern, which allowed us to increase cell height by reducing the surface area of the pattern. Whole cell dual voltage clamp was used to record g(j) of cell pairs after 3-5 days in culture. Fixation of cell pairs before removal of patch electrodes enabled preservation of cell morphology and offline identification of patched pairs. Subsequently, pairs were immunostained, and the volume of junctional Cx43 was quantified using confocal microscopy, image deconvolution, and three-dimensional reconstruction. Our results show a linear correlation between g(j) and Cx43 immunosignal within a range of 8-50 nS. PMID- 22081701 TI - Atypical Ca2+ currents in chromaffin cells from SHR and WKY rat strains result from the deficient expression of a splice variant of the alpha1D Ca2+ channel. AB - Ca(2+) currents (I(Ca)) recorded from adrenal chromaffin cells (CCs) of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats are similar to one another, but different from those recorded in other rodent species. I(Ca) in WKY/SHR CCs comprises an early, transient (I(Ca(e))) and a late, sustained component (I(Ca(s))). In Wistar CCs, I(Ca(e)) is absent, and I(Ca(s)) is of greater amplitude. Activation and steady-state inactivation of I(Ca(e)) and I(Ca(s)) in WKY/SHR CCs suggest the recruitment of at least two populations of Ca(2+) channels with different voltage dependence and kinetics. In WKY/SHR CCs, I(Ca(e)) is inhibited by nifedipine, enhanced by BAY K 8644, is not blocked by the mibefradil analog NNC 55-0396, and displays Ca(2+)-dependent inactivation and fast deactivation kinetics, suggesting that it results from the opening of L-type rather than T-type Ca(2+) channels. I(Ca(e)) properties suggest that it originates from the opening of Ca(2+) channels formed with the short splice variant (Ca(V)1.3(42A)). RT-PCR showed that expression of Ca(V)1.3(42A) mRNA is similar in both Wistar and WKY/SHR, but that the long variant (Ca(V)1.3(42)) is virtually absent in WKY/SHR. Thus I(Ca(e)) corresponds to the recruitment of Ca(V)1.3(42A) channels, unmasked by the absence of Ca(V)1.3(42) channels. Studies in WKY CCs do not report major functional alterations, despite the unusual expression pattern of Ca(V)1.3 splice variants. It remains to be established if more subtle functional alterations exist, and if the atypical splicing pattern of Ca(V)1.3 could be related to the functional and behavioral alterations reported in WKY/SHR rats, including their susceptibility to develop hypertension. PMID- 22081702 TI - Testosterone-induced relaxation of coronary arteries: activation of BKCa channels via the cGMP-dependent protein kinase. AB - Androgens are reported to have both beneficial and detrimental effects on human cardiovascular health. The aim of this study was to characterize nongenomic signaling mechanisms in coronary artery smooth muscle (CASM) and define the ionic basis of testosterone (TES) action. TES-induced relaxation of endothelium-denuded porcine coronary arteries was nearly abolished by 20 nM iberiotoxin, a highly specific inhibitor of large-conductance, calcium-activated potassium (BK(Ca)) channels. Molecular patch-clamp studies confirmed that nanomolar concentrations of TES stimulated BK(Ca) channel activity by ~100-fold and that inhibition of nitric oxide synthase (NOS) activity by N(G)-monomethyl-L-arginine nearly abolished this effect. Inhibition of nitric oxide (NO) synthesis or guanylyl cyclase activity also attenuated TES-induced coronary artery relaxation but did not alter relaxation due to 8-bromo-cGMP. Furthermore, we detected TES-stimulated NO production in porcine coronary arteries and in human CASM cells via stimulation of the type 1 neuronal NOS isoform. Inhibition of the cGMP-dependent protein kinase (PKG) attenuated TES-stimulated BK(Ca) channel activity, and direct assay determined that TES increased activity of PKG in a concentration dependent fashion. Last, the stimulatory effect of TES on BK(Ca) channel activity was mimicked by addition of purified PKG to the cytoplasmic surface of a cell free membrane patch from CASM myocytes (~100-fold increase). These findings indicate that TES-induced relaxation of endothelium-denuded coronary arteries is mediated, at least in part, by enhanced NO production, leading to cGMP synthesis and PKG activation, which, in turn, opens BK(Ca) channels. These findings provide a molecular mechanism that could help explain why androgens have been reported to relax coronary arteries and relieve angina pectoris. PMID- 22081703 TI - Cytoskeletal role in protection of the failing heart by beta-adrenergic blockade. AB - Formation of a dense microtubule network that impedes cardiac contraction and intracellular transport occurs in severe pressure overload hypertrophy. This process is highly dynamic, since microtubule depolymerization causes striking improvement in contractile function. A molecular etiology for this cytoskeletal alteration has been defined in terms of type 1 and type 2A phosphatase-dependent site-specific dephosphorylation of the predominant myocardial microtubule associated protein (MAP)4, which then decorates and stabilizes microtubules. This persistent phosphatase activation is dependent upon ongoing upstream activity of p21-activated kinase-1, or Pak1. Because cardiac beta-adrenergic activity is markedly and continuously increased in decompensated hypertrophy, and because beta-adrenergic activation of cardiac Pak1 and phosphatases has been demonstrated, we asked here whether the highly maladaptive cardiac microtubule phenotype seen in pathological hypertrophy is based on beta-adrenergic overdrive and thus could be reversed by beta-adrenergic blockade. The data in this study, which were designed to answer this question, show that such is the case; that is, beta(1)- (but not beta(2)-) adrenergic input activates this pathway, which consists of Pak1 activation, increased phosphatase activity, MAP4 dephosphorylation, and thus the stabilization of a dense microtubule network. These data were gathered in a feline model of severe right ventricular (RV) pressure overload hypertrophy in response to tight pulmonary artery banding (PAB) in which a stable, twofold increase in RV mass is reached by 2 wk after pressure overloading. After 2 wk of hypertrophy induction, these PAB cats during the following 2 wk either had no further treatment or had beta-adrenergic blockade. The pathological microtubule phenotype and the severe RV cellular contractile dysfunction otherwise seen in this model of RV hypertrophy (PAB No Treatment) was reversed in the treated (PAB beta-Blockade) cats. Thus these data provide both a specific etiology and a specific remedy for the abnormal microtubule network found in some forms of pathological cardiac hypertrophy. PMID- 22081704 TI - Aldosterone-induced brain MAPK signaling and sympathetic excitation are angiotensin II type-1 receptor dependent. AB - Angiotensin II (ANG II)-induced mitogen-activated protein kinase (MAPK) signaling upregulates angiotensin II type-1 receptors (AT(1)R) in hypothalamic paraventricular nucleus (PVN) and contributes to AT(1)R-mediated sympathetic excitation in heart failure. Aldosterone has similar effects to increase AT(1)R expression in the PVN and sympathetic drive. The present study was undertaken to determine whether aldosterone also activates the sympathetic nervous system via MAPK signaling and, if so, whether its effect is independent of ANG II and AT(1)R. In anesthetized rats, a 4-h intravenous infusion of aldosterone induced increases (P < 0.05) in phosphorylated (p-) p44/42 MAPK in PVN, PVN neuronal excitation, renal sympathetic nerve activity (RSNA), mean blood pressure (MBP), and heart rate (HR). Intracerebroventricular or bilateral PVN microinjection of the p44/42 MAPK inhibitor PD-98059 reduced the aldosterone-induced RSNA, HR, and MBP responses. Intracerebroventricular pretreatment (5 days earlier) with pooled small interfering RNAs targeting p44/42 MAPK reduced total and p-p44/42 MAPK, aldosterone-induced c-Fos expression in the PVN, and the aldosterone-induced increases in RSNA, HR, and MBP. Intracerebroventricular infusion of either the mineralocorticoid receptor antagonist RU-28318 or the AT(1)R antagonist losartan blocked aldosterone-induced phosphorylation of p44/42 MAPK and prevented the increases in RSNA, HR, and MBP. These data suggest that aldosterone-induced sympathetic excitation depends upon that AT(1)R-induced MAPK signaling in the brain. The short time course of this interaction suggests a nongenomic mechanism, perhaps via an aldosterone-induced transactivation of the AT(1)R as described in peripheral tissues. PMID- 22081705 TI - Exercise plus volume loading prevents orthostatic intolerance but not reduction in cerebral blood flow velocity after bed rest. AB - This study tested the hypothesis that reduction in cerebral blood flow (CBF) during orthostatic stress after bed rest can be ameliorated with volume loading, exercise, or both. Transcranial Doppler was used to measure changes in CBF velocity during lower body negative pressure (LBNP) before and after an 18-day bed rest in 33 healthy subjects. Subjects were assigned into four groups with similar age and sex: 1) supine cycling during bed rest (Exercise group; n = 7), 2) volume loading with Dextran infusion after bed rest to restore reduced left ventricular filling pressure (Dextran group; n = 7), 3) exercise combined with volume loading to prevent orthostatic intolerance (Ex-Dex group; n = 7), and 4) a control group (n = 12). LBNP tolerance was measured using a cumulative stress index (CSI). After bed rest, CBF velocity was reduced at a lower level of LBNP in the Control group, and the magnitude of reduction was greater in the Ex-Dex group. However, reduction in orthostatic tolerance was prevented in the Ex-Dex group. Notably, volume loading alone prevented greater reductions in CBF velocity after bed rest, but CSI was reduced still by 25%. Finally, decreases in CBF velocity during LBNP were correlated with reduction in cardiac output under all conditions (r(2) = 0.86; P = < 0.001). Taken together, these findings demonstrate that volume loading alone can ameliorate reductions in CBF during LBNP. However, the lack of associations between changes in CBF velocity and orthostatic tolerance suggests that reductions in CBF during LBNP under steady-state conditions by itself are unlikely to be a primary factor leading to orthostatic intolerance. PMID- 22081707 TI - Regulation of coronary venular barrier function by blood borne inflammatory mediators and pharmacological tools: insights from novel microvascular wall models. AB - We hypothesized that postcapillary venules play a central role in the control of the tightness of the coronary system as a whole, particularly under inflammatory conditions. Sandwich cultures of endothelial cells and pericytes of precapillary arteriolar or postcapillary venular origin from human myocardium as models of the respective vascular walls (sandwich cultures of precapillary arteriolar or postcapillary venular origin) were exposed to thrombin and components of the acutely activatable inflammatory system, and their hydraulic conductivity (L(P)) was registered. L(P) of SC-PAO remained low under all conditions (3.24 +/- 0.52.10(-8)cm.s(-1).cmH(2)O(-1)). In contrast, in the venular wall model, PGE(2), platelet-activating factor (PAF), leukotriene B(4) (LTB(4)), IL-6, and IL-8 induced a prompt, concentration-dependent, up to 10-fold increase in L(P) with synergistic support when combined. PAF and LTB(4) released by metabolically cooperating platelets, and polymorphonuclear leucocytes (PMNs) caused selectively venular endothelial cells to contract and to open their clefts widely. This breakdown of the barrier function was preventable and even reversible within 6-8 h by the presence of 50 MUM quercetin glucuronide (QG). LTB(4) synthesis was facilitated by biochemical involvement of erythrocytes. Platelets segregated in the arterioles and PMNs in the venules of blood-perfused human myocardium (histological studies on donor hearts refused for heart transplantation). Extrapolating these findings to the coronary microcirculation in vivo would imply that the latter's complex functionality after accumulation of blood borne inflammatory mediators can change rapidly due to selective breakdown of the postcapillary venular barrier. The resulting inflammatory edema and venulo thrombosis will severely impair myocardial performance. The protection afforded by QG could be of particular relevance in the context of cardiosurgical intervention. PMID- 22081706 TI - Tempol modulates changes in xenobiotic permeability and occludin oligomeric assemblies at the blood-brain barrier during inflammatory pain. AB - Our laboratory has shown that lambda-carrageenan-induced peripheral inflammatory pain (CIP) can alter tight junction (TJ) protein expression and/or assembly leading to changes in blood-brain barrier xenobiotic permeability. However, the role of reactive oxygen species (ROS) and subsequent oxidative stress during CIP is unknown. ROS (i.e., superoxide) are known to cause cellular damage in response to pain/inflammation. Therefore, we examined oxidative stress-associated effects at the blood-brain barrier (BBB) in CIP rats. During CIP, increased staining of nitrosylated proteins was detected in hind paw tissue and enhanced presence of protein adducts containing 3-nitrotyrosine occurred at two molecular weights (i.e., 85 and 44 kDa) in brain microvessels. Tempol, a pharmacological ROS scavenger, attenuated formation of 3-nitrotyrosine-containing proteins in both the hind paw and in brain microvessels when administered 10 min before footpad injection of lambda-carrageenan. Similarly, CIP increased 4-hydroxynoneal staining in brain microvessels and this effect was reduced by tempol. Brain permeability to [(14)C]sucrose and [(3)H]codeine was increased, and oligomeric assemblies of occludin, a critical TJ protein, were altered after 3 h CIP. Tempol attenuated both [(14)C]sucrose and [(3)H]codeine brain uptake as well as protected occludin oligomers from disruption in CIP animals, suggesting that ROS production/oxidative stress is involved in modulating BBB functional integrity during pain/inflammation. Interestingly, tempol administration reduced codeine analgesia in CIP animals, indicating that oxidative stress during pain/inflammation may affect opioid delivery to the brain and subsequent efficacy. Taken together, our data show for the first time that ROS pharmacological scavenging is a viable approach for maintaining BBB integrity and controlling central nervous system drug delivery during acute inflammatory pain. PMID- 22081708 TI - Prominent contribution of L-type Ca2+ channels to cutaneous neurovascular transmission that is revealed after spinal cord injury augments vasoconstriction. AB - In patients with spinal cord injury (SCI), somatosympathetic reflexes produce exaggerated decreases in skin blood flow below the lesion. This hypoperfusion appears to result from an increased responsiveness of cutaneous arterial vessels to neural activation. Here we investigated the mechanisms that underlie SCI induced enhancement of neurovascular transmission in a cutaneous vessel, the rat tail artery. Isometric contractions of arterial segments from T11 spinal cord transected and sham-operated rats were compared 6 wk postoperatively. SCI more than doubled the amplitudes of contractions of arteries in response to moderate frequencies of nerve stimulation (0.1 to 1 Hz). In arteries from SCI rats, but not those from sham-operated rats, the L-type Ca(2+) channel blocker nifedipine (1 MUM) reduced the amplitudes of nerve-evoked contractions. Furthermore, while the sensitivity to the agonists phenylephrine (alpha(1)-adrenoceptor selective) and clonidine (alpha(2)-adrenoceptor selective) did not differ significantly between arteries from SCI and sham-operated rats, nifedipine had a greater inhibitory effect on contractions to both agents in arteries from SCI rats. Although sensitivity to clonidine was unchanged, SCI selectively reduced the contribution of postjunctional alpha(2)-adenceptors to nerve-evoked contractions. In arteries from unoperated rats, the L-type channel agonist BAY K 8644 (0.1 MUM) produced a similar enhancement of nerve-evoked contraction to that produced by SCI and also selectively reduced the contribution of alpha(2)-adrenceptors to these responses. Together the findings demonstrate that the SCI-induced enhancement of neurovascular transmission in the rat tail artery can largely be accounted for by an increased contribution of L-type Ca(2+) channels to activation of the vascular smooth muscle. PMID- 22081710 TI - Corynebacterium epidermidicanis sp. nov., isolated from skin of a dog. AB - A Gram-stain-positive, pleomorphic, oxidase-negative, non-motile isolate from the skin of a dog, designated strain 410(T), was subjected to comprehensive taxonomic characterization. Comparison of the 16S rRNA gene sequences revealed that the novel isolate showed highest similarities to the type strains of Corynebacterium humireducens, Corynebacterium diphtheriae, Corynebacterium pseudotuberculosis and Corynebacterium ulcerans (96.1-96.8 %). The quinone system consisted predominantly of MK-8(H(2)) and MK-9(H(2)). The polar lipid profile of strain 410(T) contained the major compounds diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two unidentified phospholipids and four unidentified glycolipids. The polyamine pattern was composed of the major amines spermidine and spermine. In the fatty acid profile, predominantly straight chain, saturated and mono-unsaturated fatty acids were detected (C(18 : 1)omega9c, C(16 : 1)omega7c, C(16 : 0)). These chemotaxonomic traits are in agreement with those reported for representatives of the genus Corynebacterium. Strain 410(T) tested negative for diphtheria toxin. Physiological properties as well as unique traits in the polar lipid profile could be used to distinguish strain 410(T) from the most closely related species. These data suggest that strain 410(T) represents a novel species of the genus Corynebacterium, for which we propose the name Corynebacterium epidermidicanis sp. nov. The type strain is 410(T) (= DSM 45586(T) = LMG 26322(T) = CCUG 60915(T)). PMID- 22081709 TI - Mitochondrial Akt-regulated mitochondrial apoptosis signaling in cardiac muscle cells. AB - We recently reported translocation and activation of Akt in cardiac mitochondria. This study was to determine whether activation of Akt in mitochondria could inhibit apoptosis of cardiac muscle cells. Insulin stimulation induced translocation of phosphorylated Akt to the mitochondria in primary cardiomyocytes. A mitochondria-targeted constitutively active Akt was overexpressed via adenoviral vector and inhibited efflux of cytochrome c and apoptosis-inducing factor from mitochondria to cytosol and partially prevented loss of mitochondria cross-membrane electrochemical gradient. Activation of caspase 3 was suppressed in the cardiomyocytes transduced with mitochondria targeted active Akt, whereas a mitochondria-targeted dominant negative Akt enhanced activation of caspase 3. Terminal deoxynucleotidyl transferase dUTP mediated nick-end labeling assay showed that mitochondrial activation of Akt significantly reduced the number of apoptotic cells. When the endogenous Akt was abolished by LY294002, the antiapoptotic actions of mitochondrial Akt remained effective. These experiments suggested that mitochondrial Akt suppressed apoptosis signaling independent of cytosolic Akt in cardiac muscle cells. PMID- 22081711 TI - Parasphingopyxis lamellibrachiae gen. nov., sp. nov., isolated from a marine annelid worm. AB - A Gram-stain-negative, aerobic, motile, orange-pigmented, slightly halophilic, rod-shaped bacterium, designated strain JAMH 0132(T), was isolated from the trophosome of a tubeworm in Kagoshima Bay, Japan, and its taxonomic position was investigated using a polyphasic approach. The novel strain grew optimally at 28 30 degrees C and with about 2.0 % (w/v) NaCl. Chemotaxonomic analysis showed that Q-10 was the predominant respiratory quinone and that C(18 : 1)omega7c, C(16 : 0) 2-OH and C(16 : 0) were the major fatty acids. Sphingoglycolipid, phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylcholine were the major polar lipids. The genomic DNA G+C content was 60.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain JAMH 0132(T) belonged to the family Sphingomonadaceae, within the class Alphaproteobacteria. The novel strain appeared most closely related to Sphingopyxis baekryungensis SW-150(T) (95.1 % 16S rRNA gene sequence similarity) and showed less sequence similarity with representatives of the genera Blastomonas, Sphingomonas, Sphingosinicella and Novosphingobium (<94.8 %). In having no detectable polyamine, strain JAMH 0132(T) differed from members of all genera currently in the family Sphingomonadaceae. On the basis of its phenotypic properties and phylogenetic distinctiveness, strain JAMH 0132(T) represents a novel species of a new genus in the family Sphingomonadaceae for which the name Parasphingopyxis lamellibrachiae gen. nov., sp. nov. is proposed. The type strain of Parasphingopyxis lamellibrachiae gen. nov., sp. nov. is JAMH 0132(T) (= JCM 15549(T) = NCIMB 14486(T)). PMID- 22081712 TI - Kangiella taiwanensis sp. nov. and Kangiella marina sp. nov., marine bacteria isolated from shallow coastal water. AB - Two Gram-negative, heterotrophic, aerobic, marine bacteria, designated strains KT1(T) and KM1(T), were isolated from seawater samples collected from the shallow coastal regions of northern Taiwan. Cells grown in broth cultures were non flagellated rods. NaCl was required for growth. Optimal growth occurred with 2-5 % NaCl, at 25-30 degrees C and at pH 8. They grew aerobically and were not capable of anaerobic growth by fermenting D-glucose or other carbohydrates. Q-8 was the only isoprenoid quinone. The major polar lipid detected in strain KT1(T) was phosphatidylmonomethylethanolamine, whereas those detected in KM1(T) were phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine and an unidentified phospholipid. Cellular fatty acids were nearly all iso-branched, with iso-C(15 : 0) as the most abundant component (54.6-57.2 % of the total). Strains KT1(T) and KM1(T) had DNA G+C contents of 43.9 and 46.3 mol%, respectively. The two strains shared 98.1 % 16S rRNA gene sequence similarity; levels of similarity with the type strains of species of the genus Kangiella were 95.6-98.4 %. Data from the present taxonomic study conducted using a polyphasic approach revealed that the isolates could be classified as representatives of two novel species of the genus Kangiella, for which the names Kangiella taiwanensis sp. nov. (type strain KT1(T) = BCRC 80330(T) = JCM 17727(T)) and Kangiella marina sp. nov. (type strain KM1(T) = BCRC 80329(T) = JCM 17728(T)) are proposed. PMID- 22081713 TI - Arcanobacterium canis sp. nov., isolated from otitis externa of a dog, and emended description of the genus Arcanobacterium Collins et al. 1983 emend. Yassin et al. 2011. AB - A polyphasic taxonomic study was performed on an unidentified Arcanobacterium like Gram-stain-positive bacterium isolated from otitis externa of a dog. Comparative 16S rRNA gene sequencing showed that the bacterium belonged to the genus Arcanobacterium and was most closely related to the type strains of Arcanobacterium haemolyticum (97.2 %), Arcanobacterium hippocoleae (96.5 %) and Arcanobacterium phocae (96.4 %). The presence of the major menaquinone MK-9(H(4)) supported the affiliation of this strain to the genus Arcanobacterium. The polar lipid profile contained the major lipids phosphatidylcholine, diphosphatidylglycerol, phosphatidylinositol mannoside and an unidentified phospholipid (PL2). Major fatty acids were C(14 : 0), C(16 : 0), C(18 : 0), C(18 : 1)omega9c and C(18 : 2)omega6,9c/anteiso-C(18 : 0) (detected as a summed feature). C(10 : 0) and C(12 : 0) were present in minor amounts. The results of physiological and biochemical testing clearly distinguished the unknown bacterium from other species of the genus Arcanobacterium. Based on these tests, it is proposed that the unknown bacterium should be classified in the novel species Arcanobacterium canis sp. nov. The type strain of Arcanobacterium canis is P6775(T) (= CCM 7958(T) = CCUG 61573(T) = CIP 110339(T)). An emended description of the genus Arcanobacterium is also provided. PMID- 22081714 TI - Rhizobium grahamii sp. nov., from nodules of Dalea leporina, Leucaena leucocephala and Clitoria ternatea, and Rhizobium mesoamericanum sp. nov., from nodules of Phaseolus vulgaris, siratro, cowpea and Mimosa pudica. AB - Two novel related Rhizobium species, Rhizobium grahamii sp. nov. and Rhizobium mesoamericanum sp. nov., were identified by a polyphasic approach using DNA-DNA hybridization, whole-genome sequencing and phylogenetic and phenotypic characterization including nodulation of Leucaena leucocephala and Phaseolus vulgaris (bean). As similar bacteria were found in the Los Tuxtlas rainforest in Mexico and in Central America, we suggest the existence of a Mesoamerican microbiological corridor. The type strain of Rhizobium grahamii sp. nov. is CCGE 502(T) (= ATCC BAA-2124(T) = CFN 242(T) = Dal4(T) = HAMBI 3152(T)) and that of Rhizobium mesoamericanum sp. nov. is CCGE 501(T) (= ATCC BAA-2123(T) = HAMBI 3151(T) = CIP 110148(T) = 1847(T)). PMID- 22081715 TI - Burkholderia symbiotica sp. nov., isolated from root nodules of Mimosa spp. native to north-east Brazil. AB - Four strains, designated JPY-345(T), JPY-347, JPY-366 and JPY-581, were isolated from nitrogen-fixing nodules on the roots of two species of Mimosa, Mimosa cordistipula and Mimosa misera, that are native to North East Brazil, and their taxonomic positions were investigated by using a polyphasic approach. All four strains grew at 15-43 degrees C (optimum 35 degrees C), at pH 4-7 (optimum pH 5) and with 0-2 % (w/v) NaCl (optimum 0 % NaCl). On the basis of 16S rRNA gene sequence analysis, strain JPY-345(T) showed 97.3 % sequence similarity to the closest related species Burkholderia soli GP25-8(T), 97.3 % sequence similarity to Burkholderia caryophylli ATCC25418(T) and 97.1 % sequence similarity to Burkholderia kururiensis KP23(T). The predominant fatty acids of the strains were C(18 : 1)omega7c (36.1 %), C(16 : 0) (19.8 %) and summed feature 3, comprising C(16 : 1)omega7c and/or C(16 : 1)omega6c (11.5 %). The major isoprenoid quinone was Q-8 and the DNA G+C content of the strains was 64.2-65.7 mol%. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and several uncharacterized aminophospholipids and phospholipids. DNA-DNA hybridizations between the novel strain and recognized species of the genus Burkholderia yielded relatedness values of <51.8 %. On the basis of 16S rRNA and recA gene sequence similarities and chemotaxonomic and phenotypic data, the four strains represent a novel species in the genus Burkholderia, for which the name Burkholderia symbiotica sp. nov. is proposed. The type strain is JPY-345(T) (= LMG 26032(T) = BCRC 80258(T) = KCTC 23309(T)). PMID- 22081716 TI - Mongoliicoccus roseus gen. nov., sp. nov., an alkaliphilic bacterium isolated from a haloalkaline lake. AB - Two pink, non-motile, aerobic, alkaliphilic, halotolerant, Gram-negative cocci, designated MIM28(T) and MIM29, were isolated from the surface water of a haloalkaline lake on the Mongolia Plateau. The isolates grew optimally at 30-33 degrees C, at pH 8-9 and with 3-4 % (w/v) NaCl. The isolates were chemoheterotrophic and could assimilate carbohydrates, organic acids and amino acids. The major respiratory quinone was menaquinone MK-7. The major polar lipids were phosphatidylcholine and phosphatidylethanolamine. The predominant cellular fatty acids were iso-C(15 : 0) (13.8-17.5 %), anteiso-C(15 : 0) (10.5-11.2 %), iso-C(16 : 0) (9.9-13.0 %), C(16 : 0) (4.3-4.6 %), iso-C(17 : 0) (3.8-5.3 %), anteiso-C(17 : 0) (3.7-7.1 %), C(17 : 1)omega6c (4.6-6.4 %), iso-C(17 : 0) 3-OH (4.6-5.8 %), summed feature 3 (C(16 : 1)omega7c and/or C(16 : 1)omega6c; 4.0-6.4 %) and summed feature 9 (iso-C(17 : 1)omega9c and/or C(16 : 0) 10-methyl; 10.4 12.5 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolates were most closely related to Litoribacter ruber YIM CH208(T) (93.6 % 16S rRNA gene sequence similarity), the genus Echinicola (90.4-92 %) and other members of the family Cyclobacteriaceae (87.8-90 %). The DNA G+C contents of strains MIM28(T) and MIM29 were 62.8 and 62.2 mol%. On the basis of morphology, physiology, fatty acid composition, phylogeny and 16S rRNA gene sequence analysis, the isolates are assigned to a novel species of a new genus, for which we propose the name Mongoliicoccus roseus gen. nov., sp. nov.; the type strain of the type species is MIM28(T) (= ACCC 05511(T) = KCTC 19808(T)). PMID- 22081717 TI - Salinirepens amamiensis gen. nov., sp. nov., a member of the family Cryomorphaceae isolated from seawater, and emended descriptions of the genera Fluviicola and Wandonia. AB - The taxonomic position of bacterial strain AM11-6(T), isolated from seawater in Japan, was determined by using a polyphasic taxonomic approach. The strain was a strictly aerobic and Gram-staining-negative slender rod, motile by gliding. The major respiratory quinone was menaquinone-6 and the predominant cellular fatty acids were iso-C(15 : 0), iso-C(17 : 0) 3-OH, C(14 : 0) and iso-C(15 : 1) G. The polar lipid pattern indicated the presence of an unidentified phospholipid, several glycolipids and an unidentified polar lipid. The G+C content of the genomic DNA was 36.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain AM11-6(T) clustered with members of the genera Wandonia and Fluviicola in the family Cryomorphaceae of the phylum Bacteroidetes. The strain required NaCl and MgCl(2) for growth and could be differentiated from members of other genera in the family Cryomorphaceae by fatty acid composition and other phenotypic characters. On the basis of these results, we describe the novel genus and species, Salinirepens amamiensis gen. nov., sp. nov. The type strain of Salinirepens amamiensis is AM11-6(T) (= NBRC 101268(T) = NCIMB 14607(T)). Emended descriptions of the genera Fluviicola and Wandonia are also proposed. PMID- 22081718 TI - Cecembia lonarensis gen. nov., sp. nov., a haloalkalitolerant bacterium of the family Cyclobacteriaceae, isolated from a haloalkaline lake and emended descriptions of the genera Indibacter, Nitritalea and Belliella. AB - A novel Gram-staining-negative, rod-shaped, non-motile bacterium, designated strain LW9(T), was isolated from a water sample collected from Lonar Lake of Buldhana district, Maharashtra, India. Colonies and broth cultures were reddish orange due to the presence of carotenoid pigments. Strain LW9(T) was positive for catalase, ornithine decarboxylase and lysine decarboxylase activities and negative for gelatinase, oxidase, urease and lipase activities. The predominant fatty acids were iso-C(15 : 0) (31.3 %), iso-C(16 : 0) (9.3 %), anteiso-C(15 : 0) (7.3 %), iso-C(16 : 1) H (6.1 %), summed feature 3 (comprising C(16 : 1)omega7c/C(16 : 1)omega6c; 5.9 %), iso-C(17 : 1)omega9c (5.4 %) and iso-C(17 : 0) 3-OH (5.0 %). Strain LW9(T) contained MK-7 as the major respiratory quinone. The polar lipids consisted of phosphatidylethanolamine, two unidentified aminolipids and seven unidentified lipids. The DNA G+C content of strain LW9(T) was 40.5 mol%. 16S rRNA gene sequence analysis indicated that the type strains of Indibacter alkaliphilus and Aquiflexum balticum, two members of the family Cyclobacteriaceae (phylum 'Bacteroidetes') were the most closely related strains with sequence similarities of 93.0 and 94.0 %, respectively. Other members of the family Cyclobacteriaceae showed sequence similarities <93.0 %. Based on these phenotypic characteristics and on phylogenetic inference, strain LW9(T) is proposed as the representative of novel species in a new genus, Cecembia lonarensis gen. nov., sp. nov. The type strain of the type species, Cecembia lonarensis, is LW9(T) (= CCUG 58316(T) = KCTC 22772(T)). Emended descriptions of the genera Indibacter, Nitritalea and Belliella are also proposed. PMID- 22081719 TI - Pseudarcicella hirudinis gen. nov., sp. nov., isolated from the skin of the medical leech Hirudo medicinalis. AB - A pinkish-pigmented, Gram-stain-negative, rod-shaped, non-spore-forming bacterium, strain E92(T), was isolated from the skin of the medical leech Hirudo medicinalis, on R2A agar. 16S rRNA gene sequence analysis of strain E92(T) showed a relatively low 16S rRNA gene sequence similarity (93.0-93.5 %) to representatives of the genus Arcicella and 91.5-92.0 % to members of the genus Flectobacillus. The polar lipid profile was composed of the major compounds phosphatidylethanolamine, an unidentified aminophospholipid, an unidentified aminolipid and an unidentified polar lipid; glycolipids were not detected. The major quinone was menquinone MK-7, and the major compound in the polyamine pattern was spermidine. The predominant fatty acids were C(16 : 1)omega5c and C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH (detected as summed feature 3). The isolate did not contain C(14 : 0) or the hydroxyl fatty acid iso-C(17 : 0) 3-OH found in all representatives of the genera Arcicella and Flectobacillus, but did produce C(18 : 1)omega7c and 11-methyl C(18 : 1)omega7c which are not found in these two genera. The DNA G+C content of strain E92(T) was 64.4 mol%. The unique 16S rRNA gene sequence, and specific chemotaxonomic and physiological data revealed that strain E92(T) represents a new genus in the family Cytophagaceae for which we propose the name Pseudarcicella hirudinis gen. nov., sp. nov., with the type strain of the type species as E92(T) (= LMG 26720(T) = CCM 7988(T)). PMID- 22081720 TI - Bensingtonia rectispora sp. nov. and Bensingtonia bomiensis sp. nov., ballistoconidium-forming yeast species from Tibetan plant leaves. AB - Five yeast strains isolated from plant leaves collected in south-east Tibet formed cream to brownish colonies and produced asymmetrical ballistoconidia and CoQ-9 as the major ubiquinone. Sequence analysis of the 26S rRNA D1/D2 domain and the internal transcribed spacer region indicated that these strains represented two novel species of the genus Bensingtonia. The names Bensingtonia rectispora sp. nov. (type strain XZ 4C5(T) = CGMCC 2.02635(T) = CBS 10710(T)) and Bensingtonia bomiensis sp. nov. (type strain XZ 33D1(T) = CGMCC 2.02670(T) = CBS 10713(T)) are proposed for the two novel species, which are phylogenetically closely related to Bensingtonia naganoensis, Bensingtonia pseudonaganoensis and the type species of the genus, Bensingtonia ciliata. PMID- 22081721 TI - Oceanicaulis stylophorae sp. nov., isolated from the reef-building coral Stylophora pistillata. AB - A bacterial strain designated GISW-4(T) was isolated from the reef-building coral Stylophora pistillata, collected from seawater off the coast of southern Taiwan, and was characterized in this taxonomic study using a polyphasic approach. Strain GISW-4(T) was Gram-stain-negative, aerobic, beige, rod-shaped, and dimorphic, either non-motile with stalks (or prosthecae), or non-stalked and motile by means of a single polar flagellum. 16S rRNA gene sequence studies showed that the novel strain clustered with Oceanicaulis alexandrii C116-18(T) (98.9 % 16S rRNA gene sequence similarity). Strain GISW-4(T) exhibited optimal growth at 35-40 degrees C, 1-2 % (w/v) NaCl and at pH 7-9. The predominant cellular fatty acids (>10 %) were C(18 : 0), C(18 : 1)omega7c and C(18 : 1)omega7c 11-methyl. The predominant polar lipids were phosphatidylglycerol, sulfoquinovosyl diacylglycerol and two unknown phospholipids (PL1-2). The major respiratory quinones were ubiquinone Q 10 and Q-9, and the DNA G+C content was 61.6 mol%. The results of physiological and biochemical tests allowed clear phenotypic differentiation of strain GISW 4(T) from the type strain of O. alexandrii. It is evident from the genotypic, phenotypic and chemotaxonomic data that the isolate should be classified as a novel species of the genus Oceanicaulis. The name proposed for this taxon is Oceanicaulis stylophorae sp. nov., with the type strain GISW-4(T) (= LMG 25723(T) = BCRC 80207(T)). PMID- 22081722 TI - Pricia antarctica gen. nov., sp. nov., a member of the family Flavobacteriaceae, isolated from Antarctic intertidal sediment. AB - A yellow-coloured, rod-shaped, Gram-reaction- and Gram-staining-negative, non motile and aerobic bacterium, designated strain ZS1-8(T), was isolated from a sample of sandy intertidal sediment collected from the Antarctic coast. Flexirubin-type pigments were absent. In phylogenetic analyses based on 16S rRNA gene sequences, strain ZS1-8(T) formed a distinct phyletic line and the results indicated that the novel strain should be placed in a new genus within the family Flavobacteriaceae. In pairwise comparisons between strain ZS1-8(T) and recognized species, the levels of 16S rRNA gene sequence similarity were all <93.3 %. The strain required Ca(2+) and K(+) ions as well as NaCl for growth. Optimal growth was observed at pH 7.5-8.0, 17-19 degrees C and with 2-3 % (w/v) NaCl. The major fatty acids were iso-C(15 : 1) G, iso-C(15 : 0), summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c), an unknown acid with an equivalent chain-length of 13.565 and iso-C(17 : 0) 3-OH. The major respiratory quinone was MK-6. The predominant polar lipid was phosphatidylethanolamine. The genomic DNA G+C content was 43.9 mol%. Based on the phylogenetic, phenotypic and chemotaxonomic data, strain ZS1-8(T) represents a novel species in a new genus in the family Flavobacteriaceae for which the name Pricia antarctica gen. nov., sp. nov. is proposed. The type strain of the type species is ZS1-8(T) (= JCM 17291(T) = DSM 23421(T)). PMID- 22081723 TI - Luteolibacter luojiensis sp. nov., isolated from Arctic tundra soil, and emended description of the genus Luteolibacter. AB - A yellow-pigmented, Gram-reaction-negative, non-motile, aerobic bacterium, designated DR4-30(T), was isolated from tundra soil near Ny-Alesund, Svalbard Archipelago, Norway (78 degrees 58' N 12 degrees 03' E). Growth occurred at 4 28 degrees C (optimum 20-25 degrees C) and at pH 7-8 (optimum pH 7). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain DR4 30(T) belongs to the genus Luteolibacter in the family Verrucomicrobiaceae. The 16S rRNA gene sequence of this strain showed 95.4 and 94.7 % sequence similarity to those of Luteolibacter pohnpeiensis A4T-83(T) and Luteolibacter algae A5J-41 2(T), respectively. The major respiratory quinones were MK-9 and MK-10; the predominant cellular fatty acids were summed feature 3 (C(16 : 1)omega7c and/or C(16 : 1)omega6c; 20.7 %), iso-C(14 : 0) (20.3 %), C(17 : 0) (10.7 %), C(16 : 0) (8.0 %) and C(14 : 0) (6.6 %). The DNA G+C content was 57.3 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain DR4-30(T) represents a novel species of the genus Luteolibacter, for which the name Luteolibacter luojiensis sp. nov. is proposed. The type strain is DR4-30(T) (= CCTCC AB 2010415(T) = NRRL B-59669(T)). An emended description of the genus Luteolibacter is also provided. PMID- 22081725 TI - Determination of meropenem penetration into the lung from Sparse data. PMID- 22081726 TI - Growing skin: A computational model for skin expansion in reconstructive surgery. AB - The goal of this manuscript is to establish a novel computational model for stretch-induced skin growth during tissue expansion. Tissue expansion is a common surgical procedure to grow extra skin for reconstructing birth defects, burn injuries, or cancerous breasts. To model skin growth within the framework of nonlinear continuum mechanics, we adopt the multiplicative decomposition of the deformation gradient into an elastic and a growth part. Within this concept, we characterize growth as an irreversible, stretch-driven, transversely isotropic process parameterized in terms of a single scalar-valued growth multiplier, the in-plane area growth. To discretize its evolution in time, we apply an unconditionally stable, implicit Euler backward scheme. To discretize it in space, we utilize the finite element method. For maximum algorithmic efficiency and optimal convergence, we suggest an inner Newton iteration to locally update the growth multiplier at each integration point. This iteration is embedded within an outer Newton iteration to globally update the deformation at each finite element node. To demonstrate the characteristic features of skin growth, we simulate the process of gradual tissue expander inflation. To visualize growth induced residual stresses, we simulate a subsequent tissue expander deflation. In particular, we compare the spatio-temporal evolution of area growth, elastic strains, and residual stresses for four commonly available tissue expander geometries. We believe that predictive computational modeling can open new avenues in reconstructive surgery to rationalize and standardize clinical process parameters such as expander geometry, expander size, expander placement, and inflation timing. PMID- 22081727 TI - Does Telephone Audio Computer-Assisted Self-Interviewing Improve the Accuracy of Prevalence Estimates of Youth Smoking? Evidence from the UMass Tobacco Study. AB - Despite their advantage for obtaining representative samples of adolescents, telephone surveys have been regarded as inferior for collecting data on youth tobacco use because they yield lower estimates than school-based self administered surveys. Although no gold standard for smoking estimates exists, the lower estimates in telephone surveys have been attributed to underreporting due to youths' concern about parents or others overhearing their responses. Telephone audio computer-assisted self-interviewing (T-ACASI) is a cost-effective method for obtaining a representative sample of youths and provides increased privacy for the respondent. We hypothesized that using T-ACASI would encourage youths to more fully report smoking behavior compared to traditional interviewer administered telephone methods. Our analysis further assessed whether respondent age, gender, race/ethnicity, and parental attitude toward smoking moderated the relationship between survey mode and smoking reports. Using data from a statewide tobacco use survey that randomly assigned youth respondents to either T-ACASI or interviewer-administered mode, we found youths were more likely to report smoking behaviors in T-ACASI mode and that this was especially true for girls, particularly those who believed their parents would disapprove strongly of their smoking. Findings suggest that traditional telephone surveys may underestimate smoking prevalence in most girls by a factor of two, and that a technique for insuring privacy for these respondents is an important component of effective telephone survey methodology. PMID- 22081728 TI - The Social Structuring of Mental Health over the Adult Life Course: Advancing Theory in the Sociology of Aging. AB - The sociology of aging draws on a broad array of theoretical perspectives from several disciplines, but rarely has it developed its own. We build on past work to advance and empirically test a model of mental health framed in terms of structural theorizing and situated within the life course perspective. Whereas most prior research has been based on cross-sectional data, we utilize four waves of data from a nationally representative sample of American adults (Americans' Changing Lives Study) collected prospectively over a 15-year period and find that education, employment and marital status, as well as their consequences for income and health, effectively explain the increase in depressive symptoms after age 65. We also found significant cohort differences in age trajectories of mental health that were partly explained by historical increases in education. We demonstrate that a purely structural theory can take us far in explaining later life mental health. PMID- 22081729 TI - Effects of Employment-Based Programs on Families by Prior Levels of Disadvantage. AB - This study examines how welfare and employment policies affect subpopulations of low-income families that have different levels of initial disadvantage. Education, prior earnings, and welfare receipt are used to measure disadvantage. The analysis of data from experiments suggests that employment-based programs have no effects on economic well-being among the least-disadvantaged low-income, single-parent families, but they have positive effects on employment and income for the most-disadvantaged and moderately disadvantaged families. These programs increase school achievement and enrollment in center-based child care of children only in moderately disadvantaged families. The most-disadvantaged families are found to increase use of child care that is not center based. Parents in these families experience depressive symptoms and aggravation. The findings raise questions about how to support families at the lowest end of the economic spectrum. PMID- 22081730 TI - Total synthesis of (+/-)-gamma-lycorane via the electrocyclic ring closure of a divinylpyrroline. AB - A concise total synthesis of (+/-)-gamma-lycorane is described. The key step in the synthesis is the 6pi-electrocyclic ring closure of a divinylpyrroline to give a tetrahydroindole, which is subsequently hydrogenated to give the all-cis indolizidine core. PMID- 22081731 TI - Organocatalyzed enantioselective synthesis of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H chromene-3-carboxylates. AB - The organocatalyzed enantioselective synthesis of biologically active 2-amino-5 oxo-5,6,7,8-tetrahydro-4H-chromene-3-carboxylate derivatives was achieved using bifunctional cinchona alkaloids as the catalysts. Using quinine thiourea as the catalyst, the tandem Michael addition-cyclization reaction between 1,3 cyclohexanediones and alkylidenecyanoacetate derivatives gives the desired products in high yields (up to 92%) and good ee values (up to 82%). PMID- 22081732 TI - Outcome Trajectories in Drug Court: Do All Participants Have Drug Problems? AB - Graduation rates in drug courts average 50% to 70%, but it is unclear what proportion of graduates responded to the drug court services and what proportion might not have had serious drug problems upon entry. This study cluster-analyzed urine drug screen results during the first 14 weeks of treatment on 284 participants from three misdemeanor drug courts. A four-cluster solution (R(2) > .75) produced distinct subgroups characterized by (1) consistently drug-negative urine specimens (34% of the sample), (2) consistently drug-positive specimens (21%), (3) consistently missed urine specimens (26%), and (4) urine specimens that began as drug-positive but became progressively drug-negative over time (19%). These data suggest that approximately one-third of the participants might not have had serious drug problems upon entry. Approximately one-fifth appeared to respond to drug court services, and nearly one-half continued to exhibit problems after 14 weeks. Implications for adaptive programming in drug courts are discussed. PMID- 22081733 TI - Efficiency of European public higher education institutions: a two-stage multicountry approach. AB - The purpose of this study is to examine efficiency and its determinants in a set of higher education institutions (HEIs) from several European countries by means of non-parametric frontier techniques. Our analysis is based on a sample of 259 public HEIs from 7 European countries across the time period of 2001-2005. We conduct a two-stage DEA analysis (Simar and Wilson in J Economet 136:31-64, 2007), first evaluating DEA scores and then regressing them on potential covariates with the use of a bootstrapped truncated regression. Results indicate a considerable variability of efficiency scores within and between countries. Unit size (economies of scale), number and composition of faculties, sources of funding and gender staff composition are found to be among the crucial determinants of these units' performance. Specifically, we found evidence that a higher share of funds from external sources and a higher number of women among academic staff improve the efficiency of the institution. PMID- 22081734 TI - Achievement motives and emotional processes in children during problem-solving: Two experimental studies of their relation to performance in different achievement goal conditions. AB - In two studies, the influence of key emotional and motivational factors on performance in different achievement goal-type situations is examined. In study 1, based on 314 sixth-graders, two types of goal situations were induced; performance and mastery. The goals were examined with respect to important antecedents (e.g., motive dispositions) and several consequences (e.g., performance, satisfaction, pleasant affect, worry, and emotionality). The results showed that the motive to achieve success (M(s)) produced positive affects, satisfaction, and increased performance, whereas the motive to avoid failure (M(f)) produced worries and performance reduction. In study 2, based on 331 sixth graders, three types of goal situations were induced; performance-approach, performance-avoidance, and mastery goals. The findings revealed that the most important single factors positively related to performance were M(s) and mastery goal situation. In addition, high M(s) pupils performed better under mastery condition than under performance condition. Finally, avoidance-goal situation accentuate the negative effects of high M(f) on performance. PMID- 22081735 TI - Effects of orange juice pH on survival, urease activity and DNA profiles of Yersinia enterocolitica and Yersinia pseudotuberculosis stored at 4 degree C. AB - The objective of this study was to determine the survival, growth rate and possible cellular adaptation mechanisms of Y. pseudotuberculosis and Y. enterocolitica in orange juice under different pH conditions. Yersinia was inoculated in orange juice with adjusted pH levels of 3.9, 4.0, and 7.0 and stored at 4 C for 3, 24, 72 and 168 hours (h). The inter-and intra-species variation is significant to the pH and time of incubation variables (p<0.05). At 3.9 pH the CFU (colony forming units) count decreased significantly.At pH 3.9 and 4.0, Y. enterocolitica and Y. pseudotuberculosis survived for at least 30 days and 15 days, respectively. Yersinia that survived under low pH in orange juice revealed enhanced urease activity within 12 h of incubation. The attachment gene (ail) could not be detected by PCR in Y. enterocolitica from undiluted sample incubated for 24 h or longer. Moreover, the FesI-restriction profile was altered when Y. pseudotuberculosis was stored at pH 4.0 orange juice for 7 days. These results indicate that Yersinia could survive and grow at low pH and the survival mechanisms could also enable the bacteria to survive the stomach pH barrier to cause enteric infection. PMID- 22081736 TI - Measuring AIDS-Related Behaviors in Older Populations: Methodological Issues. AB - Because of a dearth of research on reporting biases in the measurement of HIV related sexual and drug use behaviors in older populations, it is frequently assumed that methodological findings of research conducted with younger populations will generalize to older respondents. In this study, estimates of the effect of the experimental manipulation of interview mode (interviewer administered vs. self-administered) were derived separately for three age strata: 12 to 49, 50 to 64, and 65+. Results of these analyses indicate that there were a number of noteworthy reversals in which interviewer-administered questioning in the older age strata produced higher esti-mates of the prevalence of substance use or alcohol-related problem behaviors. These results suggest that caution should be exercised in making generalizations from studies of reporting bias for HIV-related behaviors to older populations. PMID- 22081737 TI - Relationship-Specific Investments, Family Chaos, and Cohabitation Dissolution Following a Non-marital Birth. AB - Predictors of two types of cohabitation dissolution, dissolution with a continued romantic relationship and without (i.e. breakup), were examined using data from mothers cohabiting at the time of a non-marital birth in the Fragile Families and Child Wellbeing Study (n = 1624). Life tables indicated 64% of unions dissolved within 5 years; of these, 76% broke-up. Black mothers had the highest rates of dissolution. Maximum likelihood discrete-time event history results revealed that younger mothers were more likely to experience cohabitation dissolution into a breakup. Fewer relationship-specific investments and more family chaos were also associated with greater risk of cohabitation dissolution into a breakup. Mothers' multipartnered fertility and fewer relationship-specific investments were associated with greater risk of cohabitation dissolution with a continued romantic relationship. Post-dissolution, mothers who maintained a romantic relationship were more likely to reenter a union with their former partner while mothers whose union broke-up most often remained so. PMID- 22081738 TI - Emotions in Marital Conflict Interactions: Empathic Accuracy, Assumed Similarity, and the Moderating Context of Depressive Symptoms. AB - To examine affectivity in marital interaction, 267 couples participated in laboratory-based marital conflicts and afterward rated their own and their spouses' emotions of positivity, anger, sadness, and fear. Actor-Partner Interdependence Models (Cook & Kenny, 2005) estimated empathic accuracy and assumed similarity effects, with symptoms of depression tested as a moderator. Depressive symptoms moderated spouses' ratings of their partners' negative emotions such that assumed similarity was higher and empathic accuracy was lower in the context of elevated depressive symptoms. The results suggest that depression may influence spouses' judgments of how closely linked partner emotions are (i.e., assumed similarity) and spouses' abilities to accurately perceive their partners' negative emotions (i.e., empathic accuracy), potentially contributing to the established marital dysfunction-psychological distress cycle. PMID- 22081739 TI - Peer effects in learning HIV results. AB - How do neighbors positively or negatively influence individuals living in rural Malawi to learn their HIV results? Using data of location of homes and distance to neighbors, we measure the social network effects of neighbors' learning their HIV results on individuals own learning. Using the fact that neighbors were randomly offered monetary incentives of varying amounts to learn their HIV results, we find positive effects of neighbors attending clinics on others living nearby: a 10 percentage point increase of the percentage of neighbors (approximately 2.4 individuals) learning their HIV results increases the probability of learning HIV results by 1.1 percentage points. The strongest network effects are among closest neighbors; we find no effect among religious social networks. We also find a negative interaction between direct cash incentives and peers: the effect of peers doubles among those who were not offered any individual financial incentive to learn their HIV results. PMID- 22081740 TI - Yolk hormones and sexual conflict over parental investment in the pied flycatcher. AB - Female birds might be able to manipulate the parental effort of their male partner through elevated transfer of hormones to the eggs, since these hormones affect many chick traits that males might use as cues for adjusting the level of their investment. We experimentally studied whether female pied flycatchers Ficedula hypoleuca could manipulate male investment via yolk androgens. There is much more variation in yolk androgen levels between females than within clutches, and in order to change the androgen levels of the eggs, we swapped whole clutches between nests. To estimate the androgen levels of the clutch, we measured the androgen content of a single egg per clutch. Females did not succeed in manipulating male effort using yolk androgens, since there was no relationship between the division of parental care within a pair and either original or foster egg androgen levels. One of these relationships should have occurred if females were manipulating males. The proportion of feeding visits by the male was higher when the male was old (55%) than when he was young (45%) and females laid eggs with higher androgen levels when mated with a young male. Young males did not exhibit any responses to yolk androgen levels either, which indicates that females cannot exploit their effort more than that of old males. We suggest that females may allocate yolk androgens to adjust the growth trajectories of the chicks to poor growing conditions when mated with young males that are poor providers or occupying a poor territory. PMID- 22081741 TI - Facilitating comprehensive assessment of 12-step experiences: A Multidimensional Measure of Mutual-Help Activity. AB - Existing measures of 12-step mutual-help activity typically capture only a narrow range of experiences and combine fellowships with explicitly different substance specific emphases (e.g., Alcoholics versus Narcotics Anonymous). To help expand our knowledge in this important area, we report on the development and use of a comprehensive multidimensional measure of 12-step experiences in two clinical samples of young adults and adolescents (N=430). One-week test-retest reliability was verified on a subsample. Results indicated high content validity and reliability across seven dimensions of experience (meeting attendance, meeting participation, fellowship involvement, step work, mandated attendance, affiliation, and safety), and the measure successfully discriminated between samples on anticipated activity levels. This measure provides rich data on mutual help activities and deepens our understanding of individuals' experiences across different 12-step organizations. PMID- 22081742 TI - Automating Telephone Surveys: Using T-ACASI to Obtain Data on Sensitive Topics. AB - This paper describes a new interview data collection system that uses a personal computer equipped with a telephone interface card. This system, telephone audio computer-assisted self-interviewing or T-ACASI, offers the economy of telephone interviews while providing the privacy of self-administered questionnaires. We describe T-ACASI design considerations and operational characteristics. In addition, we present data from recent studies indicating that the T-ACASI system is stable, robust, and suitable for administering relatively long and complex questionnaires on sensitive topics, including drug use and sexual behaviors associated with HIV and other STDs. PMID- 22081743 TI - Implementing Audio-CASI on Windows' Platforms. AB - Audio computer-assisted self interviewing (Audio-CASI) technologies have recently been shown to provide important and sometimes dramatic improvements in the quality of survey measurements. This is particularly true for measurements requiring respondents to divulge highly sensitive information such as their sexual, drug use, or other sensitive behaviors. However, DOS-based Audio-CASI systems that were designed and adopted in the early 1990s have important limitations. Most salient is the poor control they provide for manipulating the video presentation of survey questions. This article reports our experiences adapting Audio-CASI to Microsoft Windows 3.1 and Windows 95 platforms. Overall, our Windows-based system provided the desired control over video presentation and afforded other advantages including compatibility with a much wider array of audio devices than our DOS-based Audio-CASI technologies. These advantages came at the cost of increased system requirements --including the need for both more RAM and larger hard disks. While these costs will be an issue for organizations converting large inventories of PCS to Windows Audio-CASI today, this will not be a serious constraint for organizations and individuals with small inventories of machines to upgrade or those purchasing new machines today. PMID- 22081744 TI - Using Touch Screen Audio-CASI to Obtain Data on Sensitive Topics. AB - This paper describes a new interview data collection system that uses a laptop personal computer equipped with a touch-sensitive video monitor. The touch-screen based audio computer-assisted self-interviewing system, or touch screen audio CASI, enhances the ease of use of conventional audio CASI systems while simultaneously providing the privacy of self-administered questionnaires. We describe touch screen audio-CASI design features and operational characteristics. In addition, we present data from a recent clinic-based experiment indicating that the touch audio-CASI system is stable, robust, and suitable for administering relatively long and complex questionnaires on sensitive topics, including drug use and sexual behaviors associated with HIV and other sexually transmitted diseases. PMID- 22081745 TI - Individuals with Fear of Blushing Explicitly and Automatically Associate Blushing with Social Costs. AB - To explain fear of blushing, it has been proposed that individuals with fear of blushing overestimate the social costs of their blushing. Current information processing models emphasize the relevance of differentiating between more automatic and more explicit cognitions, as both types of cognitions may independently influence behavior. The present study tested whether individuals with fear of blushing expect blushing to have more negative social consequences than controls, both on an explicit level and on a more automatic level. Automatic associations between blushing and social costs were assessed in a treatment seeking sample of individuals with fear of blushing who met DSM-IV criteria for social anxiety disorder (n = 49) and a non-anxious control group (n = 27) using a single-target Implicit Association Test (stIAT). In addition, participants' explicit expectations about the social costs of their blushing were assessed. Individuals with fear of blushing showed stronger associations between blushing and negative outcomes, as indicated by both stIAT and self-report. The findings support the view that automatic and explicit associations between blushing and social costs may both help to enhance our understanding of the cognitive processes that underlie fear of blushing. PMID- 22081746 TI - Reduction of Seed Dormancy in Echinacea pallida (Nutt.) Nutt. by In-dark Seed Selection and Breeding. AB - Strong seed dormancy has been an obstacle for field production of Echinacea species. Previous research on overcoming Echinacea seed dormancy has been extensive and focused on treatment methods, which involve time and expense, and are incompatible with organic production if synthetic chemicals are used. We have attempted to genetically reduce seed dormancy through selection and breeding in Echinacea, by using E. pallida as a model species. Three accessions were used in this study. Nine parent plants of each accession selected from early, in-dark germinated seeds (in-dark plants) or from late, in-light seeds (in-light plants) were planted and grouped by accession and germination treatment method for seed production through a polycross method. Germination tests indicated that these in dark plants produced seed (in-dark seed) with significantly reduced seed dormancy when tested under light or dark conditions in comparison to the seed of the in light plants (in-light seed). Among the three accessions, the in-dark seed germinated at much higher rates than did the in-light seed, more than 2* at 25 degrees C under light and up to an 83* increase in darkness, and up to an 8* increase over the corresponding parental seed lots under comparable germination conditions. In addition to these increases in germination, the in-dark seed showed early and synchronized germination as compared to the in-light seed. Since these results were achieved through only one cycle of selection and breeding, they strongly suggest that we have developed a very effective method for modifying seed dormancy in Echinacea. PMID- 22081747 TI - Sister Circles as a Culturally Relevant Intervention for Anxious African American Women. AB - Research on anxiety treatment with African American women reveals a need to develop interventions that address factors relevant to their lives. Such factors include feelings of isolation, multiple roles undertaken by Black women, and faith. A recurrent theme across treatment studies is the importance of having support from other Black women. Sister circles are support groups that build upon existing friendships, fictive kin networks, and the sense of community found among African Americans females. Sister circles appear to offer many of the components Black women desire in an anxiety intervention. In this article, we explore sister circles as an intervention for anxious African American women. Culturally-infused aspects from our sister circle work with middle-class African American women are presented. Further research is needed. PMID- 22081748 TI - PTEN-Associated Complexes: An Overview. AB - PTEN is a tumor suppressor best characterized for its role as a lipid phosphatase in antagonizing the PI3-kinase pathway. Several recent studies have identified proteins that form high molecular weight complexes with PTEN in different subcellular compartments. PTEN is critical for early embryonic development, cell proliferation, cell survival and stem cell function. The discovery of PTEN complex components may help our understanding of its biological functions. In this review, PTEN complex components, functions and their regulation will be discussed. PMID- 22081749 TI - Quantification of Thiopurine/UVA-Induced Singlet Oxygen Production. AB - Thiopurines were examined for their ability to produce singlet oxygen ((1)O(2)) with UVA light. The target compounds were three thiopurine prodrugs, azathioprine (Aza), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), and their S-methylated derivatives of 6-methylmercaptopurine (me6-MP) and 6-methylthioguanine (me6-TG). Our results showed that these thiopurines were efficient (1)O(2) sensitizers under UVA irradiation but rapidly lost their photoactivities for (1)O(2) production over time by a self-sensitized photooxidation of sulfur atoms in the presence of oxygen and UVA light. The initial quantum yields of (1)O(2) production were determined to be in the range of 0.30-0.6 in aqueous solutions. Substitution of a hydrogen atom with a nitroimidazole or methyl group at S decreased the efficacy of photosensitized (1)O(2) production as found for Aza, me6-MP and me6-TG. (1)O(2)-induced formation of 8-oxo-7,8-dihydro-2' dexyguanosine (8-oxodGuo) was assessed by incubation of 6-methylthiopurine/UVA treated calf thymus DNA with human repair enzyme 8-oxodGuo DNA glycosylase (hOGG1), followed by apurinic (AP) site determination. Because more 8-oxodGuo was formed in Tris D(2)O than in Tris H(2)O, (1)O(2) is implicated as a key species in the reaction. These findings provided quantitative information on the photosensitization efficacy of thiopurines and to some extent revealed the correlations between photoactivity and phototoxicity. PMID- 22081750 TI - Corrected Feedback: A Procedure to Enhance Recall of Informed Consent to Research among Substance Abusing Offenders. AB - This study examined the efficacy of corrected feedback for improving consent recall throughout the course of an ongoing longitudinal study. Participants (N = 135) were randomly assigned to either a corrected feedback or a no-feedback control condition. Participants completed a consent quiz 2-weeks after consenting to the host study and at months 1, 2, and 3. The corrected feedback group received corrections to erroneous responses and the no-feedback control group did not. The feedback group displayed significantly greater recall overall and in specific content areas (i.e., procedures, protections, risks/benefits). Results support the use of corrected feedback for improving consent recall. PMID- 22081751 TI - Do Research Intermediaries Reduce Perceived Coercion to Enter Research Trials Among Criminally Involved Substance Abusers? AB - We examined the efficacy of including a research intermediary (RI) during the consent process in reducing participants' perceptions of coercion to enroll in a research study. Eighty-four drug court clients being recruited into an ongoing study were randomized to receive a standard informed consent process alone (standard condition) or with an RI (intermediary condition). Before obtaining consent, RIs met with clients individually to discuss remaining concerns. Findings provided preliminary evidence that RIs reduced client perceptions that their participation might influence how clinical and judicial staff view them. This suggests that using RIs may improve participant autonomy in clinical studies. PMID- 22081752 TI - A 1.3-GHz LTS/HTS NMR Magnet-A Progress Report. AB - In this paper we present details of a 600 MHz HTS insert (H600) double pancake (DP) windings. It will first be operated in the bore of a 500 MHz LTS magnet, achieving a frequency of 1.1 GHz. Upon completion of H600, we will embark on the final phase (Phase 3B) of a 3-Phase program began in 2000: completion of a high resolution 1.3 GHz LTS/HTS magnet. In Phase 3B, the H600 will be coupled to a 700 MHz LTS magnet to achieve the ultimate frequency of 1.3 GHz. The HTS insert is composed of two concentric stacks of double pancakes, one wound with high strength BSCCO-2223 tape, the other with YBCO coated conductor. Details include conductor and coil parameters, winding procedure, DPs mechanical support and integration to the background 500 MHz LTS magnet. Test results of individual DPs in LN2 are also presented. PMID- 22081753 TI - Field Performance of an Optimized Stack of YBCO Square "Annuli" for a Compact NMR Magnet. AB - The spatial field homogeneity and time stability of a trapped field generated by a stack of YBCO square plates with a center hole (square "annuli") was investigated. By optimizing stacking of magnetized square annuli, we aim to construct a compact NMR magnet. The stacked magnet consists of 750 thin YBCO plates, each 40-mm square and 80- MUm thick with a 25-mm bore, and has a O10 mm room-temperature access for NMR measurement. To improve spatial field homogeneity of the 750-plate stack (YP750) a three-step optimization was performed: 1) statistical selection of best plates from supply plates; 2) field homogeneity measurement of multi-plate modules; and 3) optimal assembly of the modules to maximize field homogeneity. In this paper, we present analytical and experimental results of field homogeneity and temporal stability at 77 K, performed on YP750 and those of a hybrid stack, YPB750, in which two YBCO bulk annuli, each O46 mm and 16-mm thick with a 25-mm bore, are added to YP750, one at the top and the other at the bottom. PMID- 22081754 TI - Active Protection of an MgB(2) Test Coil. AB - This paper presents results of a study, experimental and computational, of a detect-and-activate-the-heater protection technique applied to a magnesium diboride (MgB(2)) test coil operated in semi-persistent mode. The test coil with a winding ID of 25 cm and wound with ~500-m long reacted MgB(2) wire was operated at 4.2 K immersed in a bath of liquid helium. In this active technique, upon the initiation of a "hot spot" of a length ~10 cm, induced by a "quench heater," a "protection heater" (PH) of ~600-cm long planted within the test coil is activated. The normal zone created by the PH is large enough to absorb the test coil's entire initial stored energy and still keeps the peak temperature within the winding below ~260 K. PMID- 22081755 TI - Estimating Causal Effects in Mediation Analysis using Propensity Scores. AB - Mediation is usually assessed by a regression-based or structural equation modeling (SEM) approach that we will refer to as the classical approach. This approach relies on the assumption that there are no confounders that influence both the mediator, M, and the outcome, Y. This assumption holds if individuals are randomly assigned to levels of M but generally random assignment is not possible. We propose the use of propensity scores to help remove the selection bias that may result when individuals are not randomly assigned to levels of M. The propensity score is the probability that an individual receives a particular level of M. Results from a simulation study are presented to demonstrate this approach, referred to as Classical + Propensity Model (C+PM), confirming that the population parameters are recovered and that selection bias is successfully dealt with. Comparisons are made to the classical approach that does not include propensity scores. Propensity scores were estimated by a logistic regression model. If all confounders are included in the propensity model, then the C+PM is unbiased. If some, but not all, of the confounders are included in the propensity model, then the C+PM estimates are biased although not as severely as the classical approach (i.e. no propensity model is included). PMID- 22081756 TI - Racial/Ethnic Differences in Effects of Welfare Policies on Early School Readiness and Later Achievement. AB - This study examined whether the effects of employment-based policies on children's math and reading achievement differed for African American, Latino and Caucasian children of welfare receiving parents, and if so, why. Two kinds of employment policies were examined: education-first programs with an emphasis on adult education and job training; and work-first programs with an emphasis on immediate employment. With data from two- and five-year follow-ups in four experimental demonstrations in Grand Rapids, Michigan (N = 591) and Riverside County, California (N = 629), there was evidence of small positive effects of the Grand Rapids and Riverside education-first programs on African American and Latino children's school readiness and math scores. An opposite pattern of effects emerged among Caucasian children. In one of the two sites, we found that Latino parents' higher levels of goals for pursuing their own education appeared to explain why their children benefited to a greater degree from the program than their Caucasian counterparts. PMID- 22081758 TI - Polymer physics of the cytoskeleton. AB - The cytoskeleton is generally visualized by light or electron microscopy as a meshwork of protein filaments that spans the space between the nuclear envelope and the plasma membrane. In most cell types, this meshwork is formed by a three dimensional composite network of actin filaments, microtubules (MT), and intermediate filaments (IF) together with the host of proteins that bind to the sides or ends of these linear polymers. Cytoskeletal binding proteins regulate filament length, crosslink filaments to each other, and apply forces to the filaments. One approach to modeling the mechanical properties of the cytoskeleton and of cell in general is to consider the elements of the cytoskeleton as polymers, using experimental methods and theoretical models developed for traditional polymers but modified for the much larger, stiffer, and fragile biopolymers comprising the cytoskeleton. The presence of motor proteins that move actin filaments and microtubules also creates a new class of active materials that are out of thermodynamic equilibrium, and unconstrained by limitations of the fluctuation-dissipation theorem. These active materials create rich opportunities for experimental design and theoretical developments. The degree to which the mechanics of live cells can usefully be modeled as highly complex polymer networks is by no means certain, and this article will discuss recent progress in quantitatively measuring cytoskeletal polymer systems and relating them to the properties of the cell. PMID- 22081759 TI - Effects of Traditional Gender Role Norms and Religious Fundamentalism on Self Identified Heterosexual Men's Attitudes, Anger, and Aggression Toward Gay Men and Lesbians. AB - Sexual prejudice and antigay anger were examined as mediators of the associations between traditional male gender norms, religious fundamentalism, and aggression toward gay men and lesbians. Participants were 201 self-identified heterosexual men recruited from the community to complete computer-administered measures of adherence to traditional male gender norms (i.e., status, toughness, antifemininity), religious fundamentalism, sexual prejudice, and frequency of aggression toward gay men and lesbians. Additionally, participants completed a structured interview designed to assess anger in response to a vignette depicting a male-male intimate relationship (i.e., partners saying "I love you," holding hands, kissing). Results showed that sexual prejudice and antigay anger partially mediated the effect of antifemininity on aggression and fully mediated the effect of religious fundamentalism on aggression. Sexual prejudice alone fully mediated the effect of status on aggression and neither sexual prejudice nor antigay anger mediated the effect of toughness on aggression. Further, results suggested that religious fundamentalism is a multifaceted construct of which some aspects increase risk for aggression toward gay men and lesbians, whereas other aspects decrease this risk. These data provide multivariate evidence from a nonprobability, community-based sample that extreme internalization of dominant cultural values can set the stage for violence toward marginalized groups. Implications for intervention programming and future research are reviewed. PMID- 22081757 TI - Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases. AB - Apoptosis is an important contributor to the pathophysiology of lung diseases such as acute lung injury (ALI) and chronic obstructive pulmonary disease (COPD). Furthermore, the cellular environment of these acute and chronic lung diseases favors the delayed clearance of apoptotic cells. This dysfunctional efferocytosis predisposes to the release of endogenous ligands from dying cells. These so called damage-associated molecular patterns (DAMPs) play an important role in the stimulation of innate immunity as well as in the induction of adaptive immunity, potentially against autoantigens. In this review, we explore the role of apoptosis in ALI and COPD, with particular attention to the contribution of DAMP release in augmenting the inflammatory response in these disease states. PMID- 22081760 TI - A Motion-Tracking Ultrasonic Sensor Array for Behavioral Monitoring. AB - The application of Kalman filtering to track subjects' movements during a behavioral experiment is discussed. Specifically, an overhead array of wireless, ultrasound sensors automatically tracks the position of a parent, child, and stranger over a 4.45 m * 4.23 m observation area. This WiPsy (Wireless sensors for Psychology research) system provides accurate, real-time quantitative metrics for psychological evaluation in lieu of traditional qualitative manual coding. Moreover, tracking subjects using ultrasound sensors is less error-prone than existing methods that track based on human coding of video. In particular, the Kalman filter, which forms the core of this tracking system, can locate targets with a mean square error of about 1.3 m(2). Overall, WiPsy strives to streamline data acquisition, processing, and analysis by providing previously unavailable assessment parameters. PMID- 22081761 TI - Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming. AB - We present a novel method for estimating tree-structured covariance matrices directly from observed continuous data. Specifically, we estimate a covariance matrix from observations of p continuous random variables encoding a stochastic process over a tree with p leaves. A representation of these classes of matrices as linear combinations of rank-one matrices indicating object partitions is used to formulate estimation as instances of well-studied numerical optimization problems.In particular, our estimates are based on projection, where the covariance estimate is the nearest tree-structured covariance matrix to an observed sample covariance matrix. The problem is posed as a linear or quadratic mixed-integer program (MIP) where a setting of the integer variables in the MIP specifies a set of tree topologies of the structured covariance matrix. We solve these problems to optimality using efficient and robust existing MIP solvers.We present a case study in phylogenetic analysis of gene expression and a simulation study comparing our method to distance-based tree estimating procedures. PMID- 22081762 TI - Increasing Flexibility in Children's Online Processing of Grammatical and Nonce Determiners in Fluent Speech. AB - Two experiments using online speech processing measures with 18- to 36-month-olds extended research by Gerken & McIntosh (1993) showing that young children's comprehension is disrupted when the grammatical determiner in a noun phrase is replaced with a nonce determiner (the car vs. po car). In Expt. 1, 18-month-olds were slower and less accurate to identify familiar nouns on nonce-article than grammatical-article trials, although older children who produced determiners in their own speech showed no disruption. However, when tested on novel words in Expt. 2, even linguistically advanced 34-month-olds had greater difficulty identifying familiar as well as newly learned object names preceded by a nonce article. Children's success in "listening through" an uninformative functor-like nonce syllable before a familiar noun was related to their level of grammatical competence, but their attention to the nonce article also varied with lexical familiarity and the overall redundancy of the processing context. PMID- 22081763 TI - Gold Micro-Flowers: One-Step Fabrication of Efficient, Highly Reproducible Surface-Enhanced Raman Spectroscopy Platform. AB - We present a new method enabling simultaneous synthesis and deposition of gold micro-flowers (AuMFs) on solid substrates in a one-pot process that uses two reagents, auric acid and hydroxylamine hydrochloride, in aqueous reaction mixture. The AuMFs deposited onto the substrate form mechanically stable gold layer of expanded nanostructured surface. The morphology of the AuMFs depends on and can be controlled by the composition of the reaction solution as well as by the reaction time. The nanostructured metallic layers obtained with our method are employed as efficient platforms for chemical and biological sensing based on surface-enhanced Raman spectroscopy (SERS). SERS spectra recorded by such platforms for p-mercaptobenzoic acid and phage lambda exhibit enhancement factors above 10(6) and excellent reproducibility. PMID- 22081764 TI - Theoretical Analysis the Optical Properties of Multi-coupled Silver Nanoshell Particles. AB - The surface plasmon resonances of silver nanoshell particles are studied by Green's function. The nanoshell system of plasmon resonances results from the coupling of the inner and outer shell surface plasmon. The shift of the nanoshell plasmon resonances wavelength is plotted against with different dielectric environments, several different dielectric cores, the ratio of the inner and outer radius, and also its assemblies. The results show that a red- and blue shifted localized surface plasmon can be tuned over an extended wavelength range by varying dielectric environments, the dielectric constants and the radius of nanoshell core respectively. In addition, the separation distances, the distribution of electrical field intensity, the incident directions and its polarizations are also investigated. The study is useful to broaden the application scopes of Raman spectroscopy and nano-optics. PMID- 22081765 TI - A cost-aggregating integer linear program for motif finding. AB - In the motif finding problem one seeks a set of mutually similar substrings within a collection of biological sequences. This is an important and widely studied problem, as such shared motifs in DNA often correspond to regulatory elements. We study a combinatorial framework where the goal is to find substrings of a given length such that the sum of their pairwise distances is minimized. We describe a novel integer linear program for the problem, which uses the fact that distances between substrings come from a limited set of possibilities allowing for aggregate consideration of sequence position pairs with the same distances. We show how to tighten its linear programming relaxation by adding an exponential set of constraints and give an efficient separation algorithm that can find violated constraints, thereby showing that the tightened linear program can still be solved in polynomial time. We apply our approach to find optimal solutions for the motif finding problem and show that it is effective in practice in uncovering known transcription factor binding sites. PMID- 22081766 TI - Choice of Biologic Therapy for Patients with Rheumatoid Arthritis: The Infection Perspective. AB - Biologicals revolutionized the treatment of Rheumatoid Arthritis (RA). The targeted suppression of key inflammatory pathways involved in joint inflammation and destruction allows better disease control, which, however, comes at the price of an elevated infection risk due to relative immunosuppression. The disease related infection risk and the infection risk associated with the use of TNF alpha inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol), rituximab, abatacept and tocilizumab are discussed. Risk factors clinicians need to take into account when selecting the most appropriate biologic therapy for RA patients, as well as precautions and screening concerning a number of specific infections, such as tuberculosis, intracellular bacterial infections, reactivation of chronic viral infections and HIV are reviewed. PMID- 22081768 TI - CRLX101 (formerly IT-101)-A Novel Nanopharmaceutical of Camptothecin in Clinical Development. AB - CRLX101 (formerly IT-101) is a first-in-class nanopharmaceutical, currently in Phase 2a development, which has been developed by covalently conjugating camptothecin (CPT) to a linear, cyclodextrin-polyethylene glycol (CD-PEG) co polymer that self-assembles into nanoparticles. As a nanometer-scale drug carrier system, the cyclodextrin polymeric nanoparticle technology, referred to as "CDP", has unique design features and capabilities. Specifically, CRLX101 preclinical and clinical data confirm that CDP can address not only solubility, formulation, toxicity, and pharmacokinetic challenges associated with administration of CPT, but more importantly, can impart unique biological properties that enhance CPT pharmacodynamics and efficacy. PMID- 22081767 TI - Cough and Asthma. AB - Cough is the most common complaint for which patients seek medical attention. Cough variant asthma (CVA) is a form of asthma, which presents solely with cough. CVA is one of the most common causes of chronic cough. More importantly, 30 to 40% of adult patients with CVA, unless adequately treated, may progress to classic asthma. CVA shares a number of pathophysiological features with classic asthma such as atopy, airway hyper-responsiveness, eosinophilic airway inflammation and various features of airway remodeling. Inhaled corticosteroids remain the most important form of treatment of CVA as they improve cough and reduce the risk of progression to classic asthma most likely through their prevention of airway remodeling and chronic airflow obstruction. PMID- 22081769 TI - Total laparoscopic hysterectomy versus total abdominal hysterectomy with bilateral salpingo-oophorectomy for endometrial carcinoma: a randomised controlled trial with 5-year follow-up. AB - This report is on recovery and long-term outcomes in a small-scale randomised controlled trial (RCT) after total laparoscopic hysterectomy versus total abdominal hysterectomy in (potential) endometrial carcinoma patients. An RCT was performed among women with atypical endometrial hyperplasia and endometrial carcinoma scheduled for hysterectomy in a teaching hospital in The Netherlands. Women were randomised to total laparoscopic hysterectomy versus total abdominal hysterectomy both with bilateral salpingo-oophorectomy and were followed until 5 years after the intervention. Patients completed the RAND 36-Item Short Form Health Survey (RAND-36), Quality of Recovery-40 (QoR-40) and Recovery Index-10 (RI-10) until 12 weeks after surgery. Main outcome measure was quality of life and recovery in the first 12 weeks after surgery. A linear mixed model was used for statistical analysis while accounting for baseline values where applicable. Seventeen women were included, of whom 11 allocated to the laparoscopic arm and 6 to the abdominal arm. Laparoscopic hysterectomy performed better on all scales and subscales used in the study. A statistically significant treatment effect, favouring laparoscopic hysterectomy, was found in the total RAND-36 (difference between groups 142 units, 95% confidence interval 46; 236). Clinical follow-up was completed after median 60 months, but this study was too small for conclusions regarding the safety and survival. Laparoscopic hysterectomy results in better postoperative quality of life in the first 12 weeks after surgery when compared with abdominal hysterectomy. PMID- 22081770 TI - THE AUTODIGESTION HYPOTHESIS AND RECEPTOR CLEAVAGE IN DIABETES AND HYPERTENSION. AB - One of the key features of cardiovascular complications, such as hypertension or diabetes, is that they often appear at the same time in the same individual together with other forms of co-morbidities. While clinically a recognized phenomenon, no molecular mechanism for such co-morbidities has received universal acceptance. We propose a new hypothesis that provides a molecular basis for co morbidities in hypertension due to unchecked proteolytic activity and receptor destruction. Testing of the hypothesis in the spontaneously hypertensive rat reveals an unchecked matrix metalloproteinase and serine protease activity in plasma and on several cardiovascular and parenchymal cells. The elevated proteolytic activity causes extracellular cleavage of multiple receptor types, such that cleavage of one receptor type leads to loss of the function carried out by this receptor. Proteolytic cleavage of the extracellular domain of the beta(2) adrenergic receptor in arteries and arterioles causes vasoconstriction and elevation of the central blood pressure while cleavage of the extracellular domain of the insulin receptor leads to insulin resistance and lack of transmembrane glucose transport. A diverse set of cell dysfunctions in the spontaneously hypertensive rat are accompanied by cleavage of the membrane receptors that are involved in these functions. Chronic inhibition of the unchecked protease activity in the spontaneously hypertensive rat serves to restore the extracellular receptor density and alleviates the corresponding cell dysfunctions. The mild unchecked proteolytic activity in the spontaneously hypertensive rat points towards a chronic autodigestion process as a contributor to the end organ injury encountered in this rat strain. The presence of various soluble receptors, which consist of extracellular fragments of membrane receptors, in the plasma of hypertensive and diabetic patients suggest that the autodigestion process may also be present in man. PMID- 22081771 TI - Tumor-stroma: In vivo assays and intravital imaging to study cell migration and metastasis. AB - The development of metastatic disease is often correlated with poor patient outcome in a variety of different cancers. The metastatic cascade is a complex, multistep process that involves the growth of the primary tumor and angiogenesis, invasion into the local environment, intravasation into the vasculature, tumor cell survival in the circulation, extravasation from the vasculature and sustained growth at secondary organ sites to form metastases. Although in vitro assays of single cell types can provide information regarding cell autonomous mechanisms contributing to metastasis, the in vivo microenvironment entails a network of interactions between cells which is also important. Insight into the mechanisms underlying tumor cell migration, invasion and metastasis in vivo has been aided by development of multiphoton microscopy and in vivo assays, which we will review here. PMID- 22081772 TI - A Neurobiological Model of Insomnia. AB - Insomnia is a common clinical condition resulting in significant costs and morbidity. Previous models of insomnia focusing on psychological and behavioral processes are useful clinically, but lack neurobiological specificity. We propose an insomnia model based on basic and clinical neuroscience findings, and hypothesize that insomnia results from persistent activity in wake-promoting neural structures during NREM sleep. The simultaneous occurrence of sleeping and waking neural activity helps to explain clinical phenomenology and treatment effects in insomnia. PMID- 22081773 TI - Physiologic Arousal to Social Stress in Children with Autism Spectrum Disorders: A Pilot Study. AB - Little is known about arousal to socially stressful situations in children with Autism Spectrum Disorders. This preliminary study investigates physiologic arousal in children with high functioning autism (HFA, n=19) compared to a comparison group (n=11) before, during, and after the Trier Social Stress Test. The HFA group was more likely to have a decrease in salivary cortisol following the stressor, while the comparison group was more likely to have an increase (p=.02). However, there was no difference in electrodermal activity, a measure of sympathetic arousal, or vagal tone, a measure of parasympathetic activity, between groups. These findings implicate a differential neuroendocrine response to social stress in children with HFA despite similar sympathetic and parasympathetic responses during a stressor. Further studies are required to substantiate this finding. PMID- 22081774 TI - What is it like to be a human? AB - The explicit link between awareness and sociality put forward in the accompanying article opens new doors to thinking about the evolutionary origins of consciousness. Human subjective experience undoubtedly has some features that are species-specific and others that are shared over a broad phylogenetic base. The authors' proposal that consciousness depends on high-level neural circuits evolved for social perception begs the question whether animals lacking such circuitry experience a fundamentally different form of consciousness from humans. It also highlights the need for comparative work elucidating neural mechanisms by which animals other than primates perceive and respond to their conspecifics. PMID- 22081775 TI - Problem Stabilization: A Metric for Problem Improvement in Home Visiting Clients. AB - BACKGROUND: Public health nurse (PHN) home visiting programs have been widely employed to improve life course trajectories for high risk mothers. Home visiting programs are often lengthy, during which PHNs simultaneously address multiple problems using diverse interventions over several client encounters. To manage PHN caseloads it is critical to understand the trajectory of client improvement and the optimal duration or services. PHN documentation data enable intervention trajectory research for specific client problems. A new metric called problem stabilization is proposed for evaluating interim improvement during PHN home visiting. Problem stabilization is an intervention pattern for a client problem that is characterized by co-occurring actions (i.e. teaching, guidance, and counseling; treatments and procedures; case management; and/or surveillance) during a client encounter; followed by surveillance actions only for that problem during a subsequent client encounter. The purpose of the study was to investigate problem stabilization during home visiting services for high risk mothers. METHODS: A retrospective cohort was created using family home visiting intervention documentation data from a local Midwest public health agency over a six year period (2000-2005). The data set consisted of Omaha System interventions for 720 high risk mothers. Analysis was conducted using descriptive statistics and Kaplan Meier curves. RESULTS: On average 30.1% of the time, client problems stabilized before discharge. Stabilization patterns differed by problem. Time to stabilization was longest for Caretaking/parenting and Antepartum/postpartum problems, and shortest for Residence and Mental health problems. CONCLUSIONS: Problem stabilization, a proposed intermediate outcome of PHN home visiting care, appears to be meaningful in describing client response to PHN intervention. This metric is an example of meaningful use of structured clinical electronic health record data for program evaluation and clinical decision support. PMID- 22081776 TI - Intervention costs and cost-effectiveness for a multiple-risk-factor diabetes self-management trial for Latinas: economic analysis of !Viva Bien! AB - Information on cost-effectiveness of multiple-risk-factor lifestyle interventions for Latinas with diabetes is lacking. The aim of this paper is to evaluate costs and cost-effectiveness for !Viva Bien!, a randomized trial targeting Latinas with type 2 diabetes. We estimated 6-month costs; calculated incremental costs per behavioral, biologic, and quality-of-life change; and performed sensitivity analyses from health plan and participant perspectives. Recruitment, intervention, and participant costs were estimated at $45,896, $432,433, and $179,697, respectively. This translates to $4,634 in intervention costs per !Viva Bien! participant; $7,723 in both per unit reduction in hemoglobin A1c and per unit reduction in body mass index. Although costs may be higher than interventions that address one risk factor, potential risks for longer-term health-care costs are high for this at-risk group. Given the benefits of !Viva Bien!, cost reductions are recommended to enhance its efficiency, adoption, and long-term maintenance without diluting its effectiveness. PMID- 22081777 TI - Human Cell Surface Receptors as Molecular Imaging Candidates for Metastatic Prostate Cancer. AB - Existing clinical imaging procedures lack sensitivity and specificity in detecting early prostate cancer bone metastatic lesions. In this study, we developed a highly reproducible bone metastasis xenograft model and identified possible molecular imaging candidates for detecting early bone metastatic lesions. Bone trophic human prostate cells (PC-3B1) were isolated and characterized for their ability to reach bone after intracardiac injection into SCID mice. The appearances of skeletal metastases were evaluated using digital radiographic imaging and confirmed by necropsy and histology. The PC-3B1 cells retain a bone homing phenotype after long term propagation in tissue culture and exhibit progressive bone lesions within 3 weeks following intracardiac injection. Comparative transcription signatures of PC-3 and PC-3B1 cells were determined using a cancer specific microarray and confirmed by RT-PCR analysis. The analysis identified increased expression of four cell surface molecules in PC-3B1 cells that may be suitable as molecular imaging candidates to detect bone micro metastases. PMID- 22081779 TI - COORDINATE DESCENT ALGORITHMS FOR NONCONVEX PENALIZED REGRESSION, WITH APPLICATIONS TO BIOLOGICAL FEATURE SELECTION. AB - A number of variable selection methods have been proposed involving nonconvex penalty functions. These methods, which include the smoothly clipped absolute deviation (SCAD) penalty and the minimax concave penalty (MCP), have been demonstrated to have attractive theoretical properties, but model fitting is not a straightforward task, and the resulting solutions may be unstable. Here, we demonstrate the potential of coordinate descent algorithms for fitting these models, establishing theoretical convergence properties and demonstrating that they are significantly faster than competing approaches. In addition, we demonstrate the utility of convexity diagnostics to determine regions of the parameter space in which the objective function is locally convex, even though the penalty is not. Our simulation study and data examples indicate that nonconvex penalties like MCP and SCAD are worthwhile alternatives to the lasso in many applications. In particular, our numerical results suggest that MCP is the preferred approach among the three methods. PMID- 22081780 TI - STATE-SPACE SOLUTIONS TO THE DYNAMIC MAGNETOENCEPHALOGRAPHY INVERSE PROBLEM USING HIGH PERFORMANCE COMPUTING. AB - Determining the magnitude and location of neural sources within the brain that are responsible for generating magnetoencephalography (MEG) signals measured on the surface of the head is a challenging problem in functional neuroimaging. The number of potential sources within the brain exceeds by an order of magnitude the number of recording sites. As a consequence, the estimates for the magnitude and location of the neural sources will be ill-conditioned because of the underdetermined nature of the problem. One well-known technique designed to address this imbalance is the minimum norm estimator (MNE). This approach imposes an L(2) regularization constraint that serves to stabilize and condition the source parameter estimates. However, these classes of regularizer are static in time and do not consider the temporal constraints inherent to the biophysics of the MEG experiment. In this paper we propose a dynamic state-space model that accounts for both spatial and temporal correlations within and across candidate intra-cortical sources. In our model, the observation model is derived from the steady-state solution to Maxwell's equations while the latent model representing neural dynamics is given by a random walk process. We show that the Kalman filter (KF) and the Kalman smoother [also known as the fixed-interval smoother (FIS)] may be used to solve the ensuing high-dimensional state-estimation problem. Using a well-known relationship between Bayesian estimation and Kalman filtering, we show that the MNE estimates carry a significant zero bias. Calculating these high dimensional state estimates is a computationally challenging task that requires High Performance Computing (HPC) resources. To this end, we employ the NSF Teragrid Supercomputing Network to compute the source estimates. We demonstrate improvement in performance of the state-space algorithm relative to MNE in analyses of simulated and actual somatosensory MEG experiments. Our findings establish the benefits of high-dimensional state-space modeling as an effective means to solve the MEG source localization problem. PMID- 22081778 TI - No acquisition: a new ambition for HIV vaccine development? AB - Development of a safe and effective prophylactic HIV-1 vaccine presents unique challenges. The pessimism following the failure of two HIV-1 vaccine concepts in clinical trials, HIV-1 gp120 and an adenovirus-based approach to induce only cellular immune responses, has been replaced by cautious optimism engendered by the RV144 trial outcome, the isolation of several new broadly reactive neutralizing monoclonal antibodies, and recent primate model data indicating prevention of viral acquisition by active or passive immunization. Intense efforts are underway to optimize immunogen design, adjuvants, and the tools for preclinical evaluation of candidate vaccines in primates, where correlates of protection can be examined in detail - as proof-of-concept for clinical trials. PMID- 22081781 TI - Risk Prediction for Prostate Cancer Recurrence Through Regularized Estimation with Simultaneous Adjustment for Nonlinear Clinical Effects. AB - In biomedical studies, it is of substantial interest to develop risk prediction scores using high-dimensional data such as gene expression data for clinical endpoints that are subject to censoring. In the presence of well-established clinical risk factors, investigators often prefer a procedure that also adjusts for these clinical variables. While accelerated failure time (AFT) models are a useful tool for the analysis of censored outcome data, it assumes that covariate effects on the logarithm of time-to-event are linear, which is often unrealistic in practice. We propose to build risk prediction scores through regularized rank estimation in partly linear AFT models, where high-dimensional data such as gene expression data are modeled linearly and important clinical variables are modeled nonlinearly using penalized regression splines. We show through simulation studies that our model has better operating characteristics compared to several existing models. In particular, we show that there is a non-negligible effect on prediction as well as feature selection when nonlinear clinical effects are misspecified as linear. This work is motivated by a recent prostate cancer study, where investigators collected gene expression data along with established prognostic clinical variables and the primary endpoint is time to prostate cancer recurrence. We analyzed the prostate cancer data and evaluated prediction performance of several models based on the extended c statistic for censored data, showing that 1) the relationship between the clinical variable, prostate specific antigen, and the prostate cancer recurrence is likely nonlinear, i.e., the time to recurrence decreases as PSA increases and it starts to level off when PSA becomes greater than 11; 2) correct specification of this nonlinear effect improves performance in prediction and feature selection; and 3) addition of gene expression data does not seem to further improve the performance of the resultant risk prediction scores. PMID- 22081782 TI - Heart Failure with Preserved Ejection Fraction: Persistent Diagnosis, Therapeutic Enigma. AB - Heart failure with preserved ejection fraction (HFPEF) is increasing in prevalence with the aging of the population, and morbidity and mortality rates are comparable to that of heart failure with reduced ejection fraction (HFREF). The diagnosis can be difficult to make, especially in older adults, stemming from the presence of multiple comorbid illnesses with confounding symptoms. New diagnostic tools have resulted in guidelines proposed to define and diagnose HFPEF. Recent literature focusing on the pathophysiology underlying this disease suggests multiple mechanisms are involved in the generation of the phenotype, such as abnormal relaxation and ventricular-vascular coupling, chronotropic incompetence, volume overload, and redistribution and /or endothelial dysfunction. Currently, no clinically proven treatments are shown to decrease morbidity and mortality in this population; however, there may be a novel multidisciplinary and multistage treatment strategy that can be studied to address this complex disease which incorporates pharmacologic and non pharmacologic therapeutics. PMID- 22081783 TI - Variability in small bowel histopathology reporting between different pathology practice settings: impact on the diagnosis of coeliac disease. AB - BACKGROUND AND AIMS: Coeliac disease (CD) diagnosis requires the detection of characteristic histological alterations of small bowel mucosa, which are prone to interobserver variability. This study evaluated the agreement in biopsy interpretation between different pathology practice types. METHODS: Biopsies from community hospitals (n=46), university hospitals (n=18) and commercial laboratories (n=38) were blindly assessed by a pathologist at our institution for differences in histopathology reporting and agreement in diagnosis of CD and degree of villous atrophy (VA) by kappa analysis. RESULTS: Agreement for primary diagnosis was very good between this institution and university hospitals (kappa=0.888), but moderate compared with community hospitals (kappa=0.465) or commercial laboratories (kappa=0.419). Diagnosis differed in 26 (25%) cases, leading to a 20% increase in CD diagnosis after review. Among those diagnosed with CD by both institutions (n=49), agreement in degree of VA was fair (kappa=0.292), with moderate agreement between the authors and commercial laboratories (kappa=0.500) and fair with university hospitals (kappa=0.290) or community hospitals (kappa=0.211). The degree of VA was upgraded in 27% and downgraded in 2%. Within different Marsh score categories, agreement was poor (kappa<0.0316) for scores 1 and 2, both missed at other centres, and fair or moderate for scores 3a and 3b. Information regarding degree of VA and intraepithelial lymphocytosis was lacking in 26% and 86% of reports and non quantifiable descriptors, eg, 'blunting' or 'marked atrophy' were prevalent. CONCLUSIONS: CD-related histological changes are underdiagnosed in community based hospitals and commercial pathology laboratories. Because incorrect biopsy interpretation can cause underdiagnosis of CD, greater CD awareness and uniformity in small bowel biopsy reporting is required among pathologists. PMID- 22081784 TI - Expression of NCAM and OCIAD1 in well-differentiated thyroid carcinoma: correlation with the risk of distant metastasis. AB - AIMS: The biomarkers representing the metastatic potential of well-differentiated thyroid carcinoma remain to be established. A study was undertaken to find whether the expression status of neural cell adhesion molecule (NCAM) and/or ovarian cancer immunoreactive antigen domain containing 1 (OCIAD1) is associated with the metastatic potential of differentiated thyroid carcinoma. METHODS: NCAM and OCIAD1 were analysed by immunohistochemistry on tissue microarrays. RESULTS: Among 214 well-differentiated thyroid carcinomas, 68 patients had distant metastases. Immunohistochemical analyses showed that the majority of benign thyroid lesions expressed NCAM while a significant proportion of thyroid carcinomas lost or had reduced NCAM expression. Both follicular and papillary carcinomas with distant metastasis had a significantly higher frequency of preserving NCAM expression. Hierarchical clustering analysis showed that OCIAD1 had significant differential expression between benign and malignant thyroid lesions. The overall metastatic-to-localised tumour ratio was higher in NCAM expressing clusters, but the difference between ratios of OCIAD1-positive and OCIAD1-negative subclusters was not significant. CONCLUSIONS: These analyses suggest that the preservation of NCAM expression in well-differentiated thyroid carcinoma is an indicator for a higher risk of distant metastasis. OCIAD1 is a potential biomarker of thyroid carcinoma but had no significant additive effect on the risk of distant metastasis. Further elucidation of the molecular mechanisms underlying the NCAM-mediated cellular processes will be beneficial for the development of effective treatments against the metastasis of thyroid carcinoma. PMID- 22081785 TI - Mucinous tumours of the ovary--primary and metastatic. PMID- 22081786 TI - Genomic gains and losses in malignant mesothelioma demonstrated by FISH analysis of paraffin-embedded tissues. AB - AIMS: Malignant mesothelioma (MM) results from the accumulation of a number of acquired genetic events at the onset. In MM, the most frequent changes were losses in 9p21, 1p36, 14q32 and 22q12, and gains in 5p, 7p and 8q24 by comparative genomic hybridisation analysis. Although the diagnostic utility of 9p21 homozygous deletion by fluorescence in situ hybridisation (FISH) analysis in MM has been reported recently, alterations of other genes have not been examined to any great extent. This study analysed the frequency of various genomic gains and losses in MM using FISH analysis. MATERIALS AND METHODS: The authors performed a FISH analysis using paraffin-embedded tissues from 42 cases of MM. RESULTS: Chromosomal losses in MM were found at 9p21 (83%), 1p36 (43%), 14q32 (43%) and 22q12 (38%), whereas gains were found at 5p15 (48%), 7p12 (38%) and 8q24 (45%). There were no cases of adenomatoid tumour, benign mesothelial multicystic tumour, reactive mesothelial hyperplasia or pleuritis showing any gains or losses. At least one genomic abnormality was identified in all cases of MM. Among various histological subtypes, the chromosomal abnormality tended to be more common in cases showing sarcomatous elements (biphasic or pure sarcomatoid) than in cases showing an epithelioid histology. CONCLUSIONS: The authors found various genomic gains and losses in MM by FISH analysis. The frequency of each genomic gain or loss examined in MM by FISH analysis almost agreed with the comparative genomic hybridisation technique in previous studies. This study suggests that genomic evaluation by FISH analysis might be helpful in distinguishing MM from benign mesothelial proliferation. PMID- 22081787 TI - Associations of Rsf-1 overexpression with poor therapeutic response and worse survival in patients with nasopharyngeal carcinoma. AB - AIMS: Deregulated chromatin remodelling often leads to aberrant gene expression in cells, thereby implicating tumour development and progression. As a subunit of remodelling and spacing factor complex, Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness in common carcinomas. However, the expression of Rsf-1 has never been reported in nasopharyngeal carcinoma (NPC). This study aimed at evaluating the expression status, associations with clincopathological variables and prognostic implications of Rsf-1 in a well-defined cohort of NPC. METHODS: Rsf-1 immunoexpression was retrospectively assessed in biopsies of 108 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The results were correlated with the clinicopathological features, therapeutic response, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-specific survival (DSS). RESULTS: Present in 49 cases (45%), Rsf-1 overexpression was associated with N(2,3) status (p=0.016), American Joint Committee on Cancer stage 3, 4 (p=0.004), and incomplete therapeutic response (p=0.041). In multivariate analyses, Rsf-1 overexpression not only emerged as the sole independent adverse prognosticator for LRFS (p=0.0002, RR 5.287) but also independently predicted worse DMFS (p=0.0011, RR 3.185) and DSS (p<0.0001, RR 4.442), along with T(3,4) (p=0.0454) and N(2,3) (p=0.0319), respectively. CONCLUSION: Rsf-1 overexpression is common and is associated with adverse prognosticators and therapeutic response, which confers tumour aggressiveness through chromatin remodelling, and represents a potential prognostic biomarker in NPC. PMID- 22081788 TI - Instituting a music listening intervention for critically ill patients receiving mechanical ventilation: Exemplars from two patient cases. AB - Music is an ideal intervention to reduce anxiety and promote relaxation in critically ill patients receiving mechanical ventilatory support. This article reviews the basis for a music listening intervention and describes two case examples with patients utilizing a music listening intervention to illustrate the implementation and use of the music listening protocol in this dynamic environment. The case examples illustrate the importance and necessity of engaging a music therapist in not only assessing the music preferences of patients, but also for implementing a music listening protocol to manage the varied and challenging needs of patients in the critical care setting. Additionally, the case examples presented in this paper demonstrate the wide array of music patients prefer and how the ease of a music listening protocol allows mechanically ventilated patients to engage in managing their own anxiety during this distressful experience. PMID- 22081789 TI - Systematic Chemical Mutagenesis Identifies a Potent Novel Apratoxin A/E Hybrid with Improved in Vivo Antitumor Activity. AB - Apratoxins are cytotoxic marine natural products that prevent cotranslational translocation early in the secretory pathway. We showed that apratoxins downregulate receptors and growth factor ligands, giving a one-two punch to cancer cells, particularly those that rely on autocrine loops. Through total synthesis, we tested the effects of amino acid substitutions, including alanine scanning, on the downregulation of receptor tyrosine kinases and vascular endothelial growth factor A (VEGF-A) and probed the stereospecificity of target engagement by epimerization of selected chiral centers. Differential effects on two types of secretory molecules suggest that the apratoxins' substrate selectivity with respect to inhibition of secretion may be tuned through structural modifications to provide tailored therapy. Our structure-activity relationship studies and medicinal chemistry efforts led to a potent inhibitor with in vivo efficacy in a colorectal tumor xenograft model without irreversible toxicity exerted by apratoxin A, demonstrating that this novel mechanism of action has therapeutic potential. PMID- 22081790 TI - Mimicking biological design and computing principles in artificial olfaction. AB - Biology has inspired solutions to many engineering problems, including chemical sensing. Modern approaches to chemical sensing have been based on the biological principle of combining cross-selective chemical sensors with a pattern recognition engine to identify odors. Here, we review some recent advances made in mimicking biological design and computing principles to develop an electronic nose. The resulting technology will have important applications in fundamental biological research, as well as in industrial, security, and medical domains. PMID- 22081791 TI - Resonant Mode Reduction in Radiofrequency Volume Coils for Ultrahigh Field Magnetic Resonance Imaging. AB - In a multimodal volume coil, only one mode can generate homogeneous Radiofrequency (RF) field for Magnetic Resonance Imaging. The existence of other modes may increase the volume coil design difficulties and potentially decreases coil performance. In this study, we introduce common-mode resonator technique to high and ultrahigh field volume coil designs to reduce the resonant mode while maintain the homogeneity of the RF field. To investigate the design method, the common-mode resonator was realized by using a microstrip line which was split along the central to become a pair of parallel transmission lines within which common-mode currents exist. Eight common-mode resonators were placed equidistantly along the circumference of a low loss dielectric cylinder to form a volume coil. Theoretical analysis and comparison between the 16-strut common-mode volume coil and a conventional 16-strut volume coil in terms of RF field homogeneity and efficiency was performed using Finite-Difference Time-Domain (FDTD) method at 298.2 MHz. MR imaging experiments were performed by using a prototype of the common-mode volume coil on a whole body 7 Tesla scanner. FDTD simulation results showed the reduced number of resonant modes of the common-mode volume coil over the conventional volume coil, while the RF field homogeneity of the two type volume coils was kept at the same level. MR imaging of a water phantom and a kiwi fruit showing the feasibility of the proposed method for simplifying the volume coil design is also presented. PMID- 22081792 TI - A measure for describing and comparing post-reproductive lifespan as a population trait. AB - 1. While-classical life-history theory does not predict post-reproductive lifespan (PRLS), it has been detected in a great number of taxa, leading to the view that it is a broadly conserved trait, and attempts to reconcile theory with these observations. We suggest an alternative: the apparently wide distribution of significant PRLS is an artifact of insufficient methods.2. PRLS is traditionally measured in units of time between each individual's last parturition and death, after excluding those individuals for whom this interval is short. A mean of this measure is then calculated as a population value. We show this traditional population measure (which we denote PrT) to be inconsistently calculated, inherently biased, strongly correlated with overall longevity, uninformative on the importance of PRLS in a population's life history, unable to use the most-commonly available form of relevant data and without a realistic null hypothesis. Using data altered to ensure that the null hypothesis is true, we find a false positive rate of 0.47 for PrT.3. We propose an alternative population measure, using life-table methods. Post-reproductive Representation (PrR) is the proportion of adult years lived which are post reproductive. We briefly derive PrR and discuss its properties. We employ a demographic simulation, based on the null hypothesis of simultaneous and proportional decline in survivorship and fecundity, to produce a null distribution for PrR based on the age-specific rates of a population.4. In an example analysis, using data on 84 populations of human and non-human primates, we demonstrate the ability of PrR to represent the effects of artificial protection from mortality and of humanness on PRLS. PrR is found to be higher for all human populations under a wide range of conditions than for any non-human primate in our sample. A strong effect of artificial protection is found, but humans under the most-adverse conditions still achieve PrR of >0.3.5. PrT should not be used as a population measure, and should be used as an individual measure only with great caution. The use of PrR as an intuitive, statistically valid and intercomparable population life-history measure is encouraged. PMID- 22081795 TI - Creating a Reinforcement Learning Controller for Functional Electrical Stimulation of a Human Arm. AB - Clinical tests have shown that the dynamics of a human arm, controlled using Functional Electrical Stimulation (FES), can vary significantly between and during trials. In this paper, we study the application of Reinforcement Learning to create a controller that can adapt to these changing dynamics of a human arm. Development and tests were done in simulation using a two-dimensional arm model and Hill-based muscle dynamics. An actor-critic architecture is used with artificial neural networks for both the actor and the critic. We begin by training it using a Proportional Derivative (PD) controller as a supervisor. We then make clinically relevant changes to the dynamics of the arm and test the actor-critic's ability to adapt without supervision in a reasonable number of episodes. PMID- 22081796 TI - Study of the antioxidant mechanisms of Trolox and eugenol with 2,2'-azobis(2 amidinepropane)dihydrochloride using ultra-high performance liquid chromatography coupled with tandem mass spectrometry. AB - The study of antioxidant mechanisms is a difficult task that involves the monitoring and identification of unknown intermediate and final products. Most of the time, the lifetime of intermediates is too short to allow their isolation and subsequent identification by nuclear magnetic resonance (NMR). The developments of ultra-high performance liquid chromatography (UHPLC) coupled with the advances in the acquisition rates of mass spectrometry could facilitate the research on antioxidant mechanisms. This work is based on the reaction involved in the Oxygen Radical Antioxidant Capacity (ORAC) and Total Radical trapping Antioxidant Parameter (TRAP) assays. Hence, the reaction between 2,2'-azobis(2 amidinepropane)dihydrochloride (AAPH) radicals and an antioxidant was carried out in the thermostatized autosampler of a chromatographic device. Then, the reaction media were injected every six minutes, and the compounds were separated by UHPLC and detected by mass spectrometry in scan mode. Nine consecutive injections were registered in a unique file, then the evolution of the reaction for one hour in a single run was monitored. In this way, the reaction mechanisms of Trolox and eugenol with AAPH were studied, leading to the detection of nine and thirteen different compounds, respectively. An exhaustive analysis of the spectra obtained in product ion scan mode led to the identification of the compounds. Most of them were species previously found in the literature, but others have never been reported, so tentative structures were suggested. All this allowed the proposal of several steps within the antioxidant mechanisms of Trolox and eugenol, showing the great performance of UHPLC-MS/MS to complement the use of NMR in antioxidant mechanistic studies. PMID- 22081794 TI - Proteasome malfunction activates macroautophagy in the heart. AB - Protein quality control (PQC) senses and repairs misfolded/unfolded proteins and, if the repair fails, degrades the terminally misfolded polypeptides through an intricate collaboration between molecular chaperones and targeted proteolysis. Proteolysis of damaged proteins is performed primarily by the ubiquitin proteasome system (UPS). Macroautophagy (commonly known as autophagy) may also play a role in PQC-associated proteolysis, especially when UPS function becomes inadequate. The development of a range of heart diseases, including bona fide cardiac proteinopathies and various forms of cardiac dysfunction has been linked to proteasome functional insufficiency (PFI). Both PFI and activation of autophagy have been observed in the heart of well-established mouse models of cardiac proteinopathy. A causal relationship between PFI and autophagic activation was suggested by a study using cultured cardiomyocytes but has not been established in the heart of intact animals. Taking advantage of an autophagy reporter, we demonstrated here that pharmacologically induced proteasome inhibition is sufficient to activate autophagy in cardiomyocytes in both intact animals and cell cultures, unveiling a potential cross-talk between the two major degradation pathways in cardiac PQC. PMID- 22081793 TI - Age-Induced Alterations in Hippocampal Function and Metabolism. AB - As the nervous system ages, a variety of changes occur in metabolism supporting glial and neuronal function, resulting in greater susceptibility to disease conditions. Changes with aging in the metabolic unit (i.e., neurons, glial cells and blood vessels) have been reported to include alterations of vascular reactivity, impaired transport of critical substrates underlying metabolism, enhanced reactive oxygen species production and alterations in calcium signaling. Some diseases are focused on the elderly, particularly cerebral ischemia, cognitive limitations, iatrogenic hypoglycemia, malignant brain tumors (i.e., glioblastoma), and Alzheimer's disease, partly due to metabolic alterations with aging. These metabolic changes with aging are discussed in light of primary theories of aging of the brain, which include mitochondrial, calcium dysfunction and enhanced oxidative damage. Here we focus on metabolic changes with aging which can influence the susceptibility of the brain to ischemia and cognitive function. Lastly, we describe treatment possibilities for these abnormal responses to aging, particularly the topic of caloric/dietary restriction, and possible mechanisms underlying this treatment direction. PMID- 22081797 TI - School discipline and disruptive classroom behavior: the moderating effects of student perceptions. AB - This study examines the relationship between school discipline and student classroom behavior. A traditional deterrence framework predicts that more severe discipline will reduce misbehavior. In contrast, normative perspectives suggest that compliance depends upon commitment to rules and authority, including perceptions of fairness and legitimacy. Using school and individual-level data from the National Education Longitudinal Study of 1988 and multilevel regression modeling, the author finds support for the normative perspective. Students who perceive school authority as legitimate and teacher-student relations as positive are rated as less disruptive. While perceptions of fairness also predict lower disruptions, the effects are mediated by positive teacher-student relations. Contrary to the deterrence framework, more school rules and higher perceived strictness predicts more, not less, disruptive behavior. In addition, a significant interaction effect suggests that attending schools with more severe punishments may have the unintended consequence of generating defiance among certain youth. PMID- 22081798 TI - The uneven patterning of welfare benefits at the twilight of AFDC: assessing the influence of institutions, race, and citizen preferences. AB - Scholars have been slow to test welfare state theories on the extensive subnational variation in the United States during the recent period of retrenchment. We assess institutional politics theories, literature on race and social policy, and public opinion arguments relative to levels of support in states' Aid to Families Dependent Children programs from 1982 until its elimination in 1996. Pooled time-series results demonstrate that the determinants of spending during retrenchment are mostly similar to those driving development and expansion. Pro-spending actors and professionalized state institutions limit benefit curtailment, while jurisdictions with larger African- American populations have lower benefits. Additionally, liberal citizens positively impact support and strengthen the effects of state institutions, but this effect is attenuated in states with larger African-American populations. PMID- 22081799 TI - Consequences of black exceptionalism? Interracial unions with blacks, depressive symptoms, and relationship satisfaction. AB - Using data from Wave 4 (2008) of the National Longitudinal Study of Adolescent Health (N = 7,466), we examine potential consequences of black exceptionalism in the context of interracial relationships among nonblack respondents. While increasing racial diversity and climbing rates of interracial unions have fostered the notion that racial boundaries within the United States are fading, our results add to the accumulating evidence that racial/ethnic boundaries persist in U.S. society. Results suggest that among non-Black respondents there is more stigma and disapproval attached to relationships with Blacks than there are to relationships with members of other racial/ethnic groups. Specifically, our results indicate that nonblack individuals with black partners have significantly more depressive symptoms and less relationship satisfaction than their counterparts with nonblack partners, regardless of respondent race and whether the nonblack partner is the same versus a different race from the respondent. Further, the relationship between partner race and depressive symptoms is partially and significantly mediated by relationship satisfaction. PMID- 22081800 TI - Limited access: gender, occupational composition, and flexible work scheduling. AB - The current study draws on national data to explore differences in access to flexible work scheduling by the gender composition of women's and men's occupations. Results show that those who work in integrated occupations are more likely to have access to flexible scheduling. Women and men do not take jobs with lower pay in return for greater access to flexibility. Instead, jobs with higher pay offer greater flexibility. Integrated occupations tend to offer the greatest access to flexible scheduling because of their structural locations. Part-time work is negatively associated with men's access to flexible scheduling but positively associated with women's access. Women have greater flexibility when they work for large establishments, whereas men have greater flexibility when they work for small establishments. PMID- 22081801 TI - The evolution of infectious agents in relation to sex. Proceedings of a symposium. October 21-23, 2010. Karlskoga, Sweden. PMID- 22081802 TI - Proceedings of the 131st Annual Meeting of the American Surgical Association. April 14-16, 2011. Boca Raton, Florida, USA. PMID- 22081803 TI - Best practices in systems interventions to reduce the burden of fractures. Proceedings of the Bone Health Conference. December 9-10, 2010. Washington, D.C., USA. PMID- 22081804 TI - [Not Available]. PMID- 22081805 TI - Proceedings of the Eighth International Nanomedicine and Drug Delivery Symposium (NanoDDS'10). October 3-5, 2010. Omaha, Nebraska, USA. PMID- 22081806 TI - Proceedings of the Sixth International Symposium on Interventional Electrophysiology in the Management of Cardiac Arrhythmias. September 24-26, 2010. Newport, Rhode Island. PMID- 22081807 TI - Festschrift to mark the retirement of Professor Bernard Gilmartin. Proceedings of a 2-day conference. September 2011. Birmingham, United Kingdom. PMID- 22081808 TI - The lateral sacral triangle--a decision support for secure transverse sacroiliac screw insertion. AB - Sacroiliac (SI) screw fixation represents an effective method to stabilise pelvic injuries. However, to date neither reliable radiological landmarks nor effective anatomical classifications of the sacrum exist. This study investigates the influence of variability in sacral shape on secure transverse SI-screw positioning. Furthermore, consistent correlations of these anatomical conditions are analysed with respect to standard planar pelvic views. For shape analysis, 80 human computed tomography data sets were segmented with the software Amira 4.2 to obtain 3D reconstructions. We identified anatomical conditions (ACs) according to the extent of the effect on the bony screw pathway. Subsequently, the pelvis was spatially aligned using representative bone protuberances in order to create standard Matta projections. In each view, the ACs were described in terms of distance from bone landmarks. Three-dimensional shape analysis revealed the height of the pedicular isthmus (PH) as the limiting variable for secure screw insertion. The lateral and outlet views allowed an orthogonal projection of PH. In the lateral view, the ratio of the lateral sacral triangle framed by the S1 body height and width showed a high correlation to PH (p = 0.0001). A boundary ratio of 1.5 represented a reliable variable to determine whether or not a screw can be inserted (positive predictive value: 97%). In the outlet view, the distance between the S1 endplate and the SI joint top level (EJ) strongly correlated with PH (p = 0.0001). With EJ 0 mm, screw insertion was possible in all cases (100%). SI-screw insertion requires a well-planned procedure. Orientation of the sacral pedicle is of extreme relevance. A narrow sacroiliac channel and high sacral shape variability limit secure screw placement. However, no determining parameters exist, allowing accurate prediction of secure screw insertion based on X-rays or fluoroscopy. The lateral sacral triangle in the lateral view represents a simple and accurate preoperative method of support for the surgeon's decision to undertake this procedure. No additional technical effort is necessary. A boundary ratio of 1.5 predicts a sufficient bone stock for at least one 7.3 mm screw. Furthermore, the evaluation of the outlet projection can be used to assess the safety of the operation. Basically, a preoperative lateral pelvic image should be mandatory. PMID- 22081809 TI - Treatment algorithm for complex injuries of the foot in paediatric patients. AB - BACKGROUND: Complex injuries of the foot in the paediatric population present difficult treatment challenges. While standardised protocols exist for the adult population to achieve an optimal result in the treatment of such injuries, therapy in paediatric patientsmust be managed without a firm treatment algorithm. METHODS: Medical records of all patients with a complex trauma of the foot treated at our Department over a period of 13 years were evaluated. A complex trauma of the foot was defined using the scoring system developed by Zwipp et al. (1997).24 Treatment and outcome were analysed. Additionally, our treatment algorithm of complex injuries of the foot in paediatric patients is presented. RESULTS: Twenty-nine patients were included in the study (79%m; 21% f, average age 12.1 years, ranging 2-16 years). Traffic accidents were the most common mechanism (n = 14; 48.3%), followed by a fall from a height in five patients (17.2%). Lawnmower injuries were found in another 3 patients (10.3%) and other mechanisms of injury in 7 patients (24.2%). The mean score according to Zwipp et al. (1997)24 was 5.8 points (range 5-8 points). While closed fractures were diagnosed in 20 (69%) patients, 9 patients (31%) presented open fractures. Operative intervention was necessary in 24 patients (82.8%). Fracture stabilisation could be realised using K-wires in 13 cases (54.2%), screws in 3 cases (12.5%) and plate fixation in 1 case (4.2%). Combined techniques including external fixation were applied in another 7 (29.1%) cases. The mean time between injury and latest follow-up examination was 5.7 years (range 13 months to 13 years). The mean functional outcome was 47.6 (29-56) points for the OAFQ, 15.1 (0 69) points for the FFI and 82.3 (59-100) points for the AOFAS Score. DISCUSSION: To regard the maxims in treating complex injuries and open fractures in the growing skeleton we developed a simple treatment algorithm for complex foot injuries in order to provide preservation of the soft tissue envelope, avoidance of infection, restoration of the axis and the articular surface. CONCLUSION: A complex trauma of the paediatric foot is a rare and challenging injury. Avoidance of infection, preservation of the soft tissue envelope and fracture healing will provide good functional outcome despite the severity of trauma. Long time follow up is essential to detect complications. PMID- 22081810 TI - Induction of senescence in melanoma: thinking outside the cell. PMID- 22081811 TI - Serine biosynthesis: fuel for the melanoma cell growth engine. PMID- 22081812 TI - A DUB for MITF: no myth, some dubiety. PMID- 22081813 TI - Cardiac injury and troponin testing after orthopaedic surgery. AB - BACKGROUND: Cardiac injury after orthopaedic surgery is an increasing problem particularly in an ageing population. The detection of cardiac injury has been aided by the use of cardiac troponins which has also raised questions about the utility of this enzyme in the post-operative setting. OBJECTIVE: This review evaluates the diagnosis and pathophysiology of myocardial infarction after orthopaedic surgery and examines how myocardial injury is detected, with particular emphasis on the role of troponin testing. SUBJECTS: Eight recent orthopaedic trials evaluating the use of troponin were identified in the literature and included in this review. RESULTS: This review found that the diagnosis of myocardial infarction ismore difficult after surgery since classic symptoms may be atypical or absent. Therefore, there ismore reliance on the typical rise and fall in troponin to diagnose cardiac injury especially because electrocardiograph changes may be hard to detect. The pathophysiology of ischaemia after orthopaedic surgery may be different to ischaemia in the non surgical setting. The incidence of troponin elevation is between 22 and 52.9% after emergency orthopaedic operations. Of note, patients sustaining a troponin elevation are often asymptomatic. Small studies have found troponin to be a prognostic marker of in-hospital cardiac complications, increased length of stay, increased likelihood of discharge to residential care and death at 1 year. No interventional studies have been published to date. CONCLUSION: Cardiac injury is an important complication after orthopaedic surgery. Studies have found that troponin testing can detect asymptomatic cardiac injury. These patients are at risk of poorer outcomes and future research should be directed towards treatment of these patients. PMID- 22081814 TI - Cold and desiccation tolerance. Festschrift honoring Karl Erik Zachariassen. PMID- 22081816 TI - Proceedings of the 57th International Congress of Meat Science and Technology (57th ICoMST). August 7-12, 2011. Ghent, Belgium. PMID- 22081815 TI - Urgent thoracotomy for penetrating chest trauma: analysis of 158 patients of a single center. AB - BACKGROUND: Penetrating injuries to the chest present a frequent and challenging problem, but the majority of these injuries can be managed non-?operatively. The aim of this study was to describe the incidence of penetrating chest trauma and the ultimate techniques used for operative management, as well as the diagnosis, complications, morbidity and mortality. METHODS: A retrospective 9-year review of patients who underwent an operative procedure following penetrating chest trauma was performed. The mechanism of injury, gender, age, physiological and outcome parameters, including injury severity score (ISS), chest abbreviated injury scale (AIS) score, lung injury scale score, concomitant injuries, time from admission to operating room, transfusion requirement, indications for thoracotomy, intra operative findings, operative procedures, length of hospital stay (LOS) and rate of mortality were recorded. RESULTS: A total of 1123 patients who were admitted with penetrating thoracic trauma were investigated. Of these, 158 patients (93 stabbings, 65 gunshots) underwent a thoracotomy within 24 h after the penetrating trauma. There were 146 (92.4%) male and 12 (7.6%) female patients, and their mean age was 25.72 9.33 (range, 15-54) years. The mean LOS was 10.65 8.30 (range, 5 65) days. Patients admitted after a gunshot had a significantly longer LOS than those admitted with a stab wound (gunshot, 13.53 9.92 days; stab wound, 8.76 6.42 days, p < 0.001). Patients who died had a significantly lower systolic blood pressure (SBP) on presentation in the emergency room (42.94 36.702 mm Hg) compared with those who survived (83.96 27.842 mm Hg, p = 0.001). The overall mortality rate was 10.8% (n = 17). Mortality for patients with stab wounds was 8/93 (8.6%) compared with 9/65 (13.8%) for patients with gunshot wounds (p = 0.29). Concomitant abdominal injuries (p = 0.01), diaphragmatic injury (p = 0.01), ISS (p = 0.001), chest AIS score (p < 0.05), ongoing output (p = 0.001), blood transfusion volume (p < 0.01) and SBP (p = 0.001) were associated with mortality. CONCLUSION: Penetrating injuries to the chest requiring a thoracotomy are uncommon, and lung-sparing techniques have become the most frequently used procedures for lung injuries. The presence of associated abdominal injuries increased the mortality five-fold. Factors that affected mortality were ISS, chest AIS score, SBP, ongoing chest output, blood transfusion volume, diaphragmatic injury and associated abdominal injury. PMID- 22081817 TI - [Tuberculosis in HIV infected]. PMID- 22081818 TI - Effects of bilateral adrenalectomy on the innate immune responses following trauma in rats. AB - BACKGROUND: The regulation of neuroendocrine hormones on the innate immune responses in trauma has not been fully understood. Previous studies have shown that the neuroendocrine hormones are important factors in their effects on immune parameters, depending on their concentration and timing instead of the simple suppressive effects. MATERIALS AND METHODS: A total of 144 Sprague-Dawley rats were divided randomly into sham, pulmonary blast injury (BI) and adrenalectomy plus pulmonary BI groups. Bilateral adrenalectomy was performed on rats, which were then subjected to blast injury. Following this, peripheral leucocyte responsiveness to lipopolysaccharide (LPS) stimulation, phagocytosis activities of macrophages and bacteria translocation (BT) were examined. Tumour necrosis factor-a (TNF-a) levels and the expression levels of scavenger receptor (SR) A, CD14, Toll-like receptor (TLR) 4 and MD2 were assayed with enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction, respectively. RESULTS: In adrenalectomised rats after pulmonary BI, the number of peripheral leucocytes was increased and the phagocytosis of peritoneal and splenic macrophages was decreased as compared to the BI group. Simultaneously, the gut-derived BT and TNF-a secretion in lung tissues were elevated, whilst the LPS-stimulated TNF-a synthesis by peripheral leucocyte responsiveness was reduced. Furthermore, the mRNA levels of SR-A, CD14, TLR4 and MD2 in lung tissues of adrenalectomised rats decreased. Adrenalectomised rats showed enhancement of inflammatory responses and severe tissue injuries in trauma. CONCLUSIONS: Release of adrenal hormones might enhance, rather than inhibit, the innate immune functions, particularly in the early stages of trauma. PMID- 22081819 TI - Light therapy by blue LED improves wound healing in an excision model in rats. AB - BACKGROUND: Low level light therapy (LLLT) is an attractive alternative to enhance wound healing. So far most studies are performed with red or infrared irradiation. However, we recently showed that blue light (470 nm) can significantly influence biological systems, improving perfusion by release of nitric oxide from nitrosyl complexes with haemoglobin in a skin flap model in rats. Here, we compared the effects of blue and red low level light by light emitting diodes (LEDs) on in vivo wound healing in an excision wound model in rats. METHODS: Circular excision wounds were surgically created on the dorsum of each rat. Excisions on either the left or right side were illuminated post-OP and on five consecutive days for 10 min by LED at 470 nm or 630 nm with an intensity of 50 mW/cm(2),while protecting the contralateral side from exposure. In the control group, neither side was illuminated. On day 7 post-OP, we analysed planimetric and histological parameters, as well as expression of keratin-1, keratin-10 and keratin-17 on mRNA level. RESULTS: Illumination substantially influenced wound healing. Blue light significantly decreased wound size on day 7, which correlated with enhanced epithelialisation. Light also affected mRNA expression. Both wavelengths decreased keratin-1 mRNA on day 7 post-OP, while keratin-10 mRNA level was elevated in both light treated group compared to control. Keratin-17 mRNA was also elevated in the red light group, but was unchanged in the blue light group. CONCLUSION: In contrast to previous studies, we showed that also blue light significantly influences wound healing. Furthermore, our data suggest that light therapy can play an important role in normotrophic wound healing by affecting keratin expression. Illumination would provide an easily applicable, safe and cost-effective treatment of surface wounds. PMID- 22081820 TI - Laccase mediator systems for eco-friendly production of medium-density fiberboard (MDF) on a pilot scale: physicochemical analysis of the reaction mechanism. AB - Increasing prices of petrochemical resins and possible harmful formaldehyde emissions from conventionally produced wood composites have resulted in increased interest in enzymatic binder systems as environmentally friendly alternatives for gluing lignocellulosic products. In this study, laccase mediator systems (LMSs) were used to activate lignin on wood fiber surfaces in the pilot-scale production of medium-density fiberboard (MDF) using a dry process. Three different mediators were applied: 4-hydroxybenzoic acid (HBA), 1-hydroxybenzotriazole (HBT), and acetosyringone (AS) of which HBA performed best. The mechanical properties of the manufactured boards produced with thermomechanical pulp (TMP) fibers, laccase, and HBA fulfilled all required European standards for wood-based panels. Oxygen consumption rates of the different LMSs and (13)C NMR spectroscopy results for treated TMP fibers were obtained for qualitative and quantitative analysis of lignin activation. The results show that reactions were most effective within the first 30 min of incubation. Oxygen consumption was fastest and highest for the LMS using HBA. (13)C NMR spectroscopy indicated the highest decrease of aromatic groups in the wood fiber lignin with this LMS. The data correlated well with the quality of the MDF. The required enzymatic reaction times allowed direct integration of the LMS into standard MDF production techniques. The results indicate that application of LMSs has a high potential for environmentally friendly MDF production. PMID- 22081821 TI - Alcohol-related injury visits: do we know the true prevalence in U.S. trauma centres? AB - INTRODUCTION: Alcohol consumption is a significant risk factor for injuries. Further, level I trauma centres are mandated to screen and provide a brief intervention for identified problem drinkers. However, a valid population-based estimate of the magnitude of the problem is unknown. Therefore, the goal of this study is to evaluate the extent to which the present literature provides a valid estimate of the prevalence of alcohol-related visits to U.S. trauma centres. METHODS: A Medline search for all articles from 1966 to 2007 that might provide prevalence estimates of alcohol-related visits to U.S. trauma centres yielded 836 articles in English language journals. This review included only papers whose main or secondary goal was to estimate the prevalence of positive blood alcohol concentration (BAC) or acute intoxication. Both a crude aggregate estimate and sample size adjusted estimate were calculated from the included papers and the coverage and comparability of methods were evaluated. RESULTS: Of the 15 studies that met inclusion criteria, incidence estimates of alcohol-related visits ranged from 26.2% to 62.5% and yielded an aggregate, weighted estimate of 32.5%. Target population, capture rate, and threshold for a positive screening result varied considerably across studies. No study provided a comprehensive estimate, i.e., of all trauma patients hospitalised, treated and released, or who died. CONCLUSIONS: Although the incidence of alcohol-related visits to U.S. trauma centres appears very high perhaps higher than any other medical setting, the validity of our aggregate estimate is threatened by crucial methodological considerations. The lack of a methodologically valid prevalence estimate hinders efforts to devise appropriate policies for trauma centres and across medical settings. PMID- 22081823 TI - Proceedings of the Texas Tuberculosis Research Symposium. February 7, 2009. Houston, Texas, USA. PMID- 22081822 TI - The association of compensation on longer term health status for people with musculoskeletal injuries following road traffic crashes: emergency department inception cohort study. AB - OBJECTIVE: To compare the health status of people claiming compensation for injuries sustained in road traffic crashes (RTC), with people who do not claim compensation. DESIGN: Prospective cohort study. SETTING: Australian Capital Territory, Australia and a fault based common law compensation scheme. SUBJECTS: People presenting to the emergency department with mild to moderate musculoskeletal injury following RTC. MAIN OUTCOME MEASURES: Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form 36 (SF-36) health status measure, Hospital Anxiety and Depression Scale (HADS) and the Functional Rating Index (FRI). These measures are recorded immediately post crash, at 6 and 12 months post crash. RESULTS: 95 people participated in the study and were enrolled a mean of 8.6 (median 8) days following the crash. 86% were followed up to 12 months after injury. Mean age was 37 years, 61% were female and 91% were employed at the time of their injury.33%ultimately claimed compensation, and 25% engaged a lawyer. There were no major differences in baseline personal characteristics or injury related factors between the groups. As expected, involvement as a passenger and in multiple vehicle crashes, were more frequent in the group claiming compensation. Over the duration of the study claiming compensation was associated with lower SF-36 PCS (5.5 (95%CI 8.6 to 2.4), p = 0.001), greater HADS-Anxiety (1.7 (95%CI 0.2-3.3), p = 0.048), and worse FRI (11.2 (95%CI 3.9-18.5), p = 0.003). There was a highly significant improvement in health status between baseline and 6 months after injury, but no further significant change between 6 and 12 months after injury. There was no difference in rate of improvement between the groups. Claiming compensation and psychological factors were independent predictors of worse health status at 12 months. CONCLUSION: In this study the group claiming compensation had overall worse health status following mild to moderate musculoskeletal injuries over the course of the study. There was no difference in rate of improvement between the groups. However, it is not possible to determine whether this negative effect was due to claiming compensation itself or the presence of other unmeasured factors. PMID- 22081824 TI - Temporal variation in childhood injury from common recreational activities. AB - BACKGROUND/PURPOSE: To investigate the month and day of the week of injury in common childhood activities using the National Electronic Injury Surveillance System database. METHODS: All emergency department visits 2002-2006 from bicycles/tricycles, scooters, playground equipment, swimming/water activities, skiing/snowboarding, trampolines, and skating were analysed. The NEISS weighted and stratified data set was analysed using SUDAAN software. Weekday and month of injury, gender, race, anatomical location of the injury, geographical location of injury, and disposition were tabulated. Simple variation by month or weekday was analysed using cosinor analysis; combined variation for both month and weekday was analysed by topographical analysis. RESULTS: There were an estimated 4.61 million emergency department visits for injuries from these activities in children in the United States. The average age was 9.5 years; there were 1.65 million girls (35.9%) and 2.97 boys (64.1%). Cosinor analysis demonstrated significant single peaks for month of injury for snow activities (January 27), trampolines (June 10), scooters (June 24), cycling (July 6), and water (July 12) activities. Double cosinor peaks were noted for skating (April 13 and September 12) and playground (April 22 and September 21) activities. Cosinor analyses demonstrated that the peak week days of injury were Monday for trampoline and snow activities, Saturday/Sunday for skating activities, Sunday for cycling, and Wednesday for playground equipment. There was no peak injury day for scooter or water activities. Topographical representation of paediatric injuries demonstrated that injuries from slides most frequently occurred April-May on Wednesdays and Saturdays, and those on swings April-May all days except Tuesday. Monkeybar injuries were bimodal, with the spring peak on Wednesday-Thursday in April/May and the fall peak Tuesday-Friday in September. Rollerblade injuries occurred Saturday-Sunday from March/April; rollerskates on Saturday-Sunday in January-April, and skateboards Saturday-Monday in August-October and Sundays in April. CONCLUSIONS: These findings can be used to further guide childhood injury prevention programmes/campaigns and especially track improvements after targeted prevention programmes. Public parks and schools should check/correct the status of playground landing surfaces just before the bimodal peaks. Education campaigns reinforcing the need for bicycle helmets could be concentrated immediately before the increase in cycling activity - March on weekends and April/May for weekdays. PMID- 22081825 TI - Special issue dedicated to Chad Mirkin in celebration of 20 years of influential research at Northwestern University. PMID- 22081826 TI - US lawsuit extends thalidomide's reach. PMID- 22081827 TI - Dragon offers ticket to Mars. PMID- 22081829 TI - [Abstracts of the VIth Latin American Congress for Treatment and Research in Multiple Sclerosis. August 12-14, 2010. Santiago, Chile]. PMID- 22081828 TI - Abstracts of the 114th Annual Congress and 41st Annual AOSA (American Optometric Student Association) Conference. June 2011. Salt Lake City, Utah, USA. PMID- 22081830 TI - Internal jugular thrombus revealed by fine-needle aspiration to be metastatic papillary thyroid carcinoma. PMID- 22081831 TI - The lower hemoglobin A(1c) value for the screening of prediabetes. PMID- 22081832 TI - Use of insulin detemir and insulin glargine during pregnancy: are the data convincing? PMID- 22081833 TI - Traces: making sense of urodynamics testing--part 7: Evaluation of bladder filling/storage: Evaluation of urethral sphincter incompetence and stress urinary incontinence. AB - The "Traces" series discusses how the urodynamic clinician generates usable data from a filling cystometrogram. Part 7 focuses on the question, "Is the urethral sphincter mechanism competent?" From a practical viewpoint, this question can be divided into two queries: 1) does this patient have observable urodynamic stress urinary incontinence (SUI), and 2) does this patient have intrinsic urethral sphincter incompetence, also referred to as intrinsic sphincter deficiency or a low pressure urethra? Signs of SUI include clinician observation of urine loss with coughing or during Valsalva's maneuver. Urodynamic SUI is the observation of urine loss with increased abdominal and intravesical pressures in the absence of a detrusor contraction. The most commonly used techniques for assessment of urethral sphincter function and SUI are the urethral pressure profile and the abdominal leak point pressure. Both are useful for answering these queries, but both tests are vulnerable to physiologic and technical artifacts that must be minimized to produce technically accurate and clinically meaningful results. PMID- 22081834 TI - The new urban politics as a politics of carbon control. AB - The new urban politics (NUP) literature has helped to draw attention to a new generation of entrepreneurial urban regimes involved in the competition to attract investment to cities. Interurban competition often had negative environmental consequences for the urban living place. Yet knowledge of the environment was not very central to understanding the NUP. Entrepreneurial urban regimes today are struggling to deal with climate change and reductions in greenhouse gas emissions. Carbon reduction strategies could have profound implications for interurban competition and the politics of urban development. This paper explores the rise of a distinctive low-carbon urban polity-carbon control-and examines its potential ramifications for a new environmental politics of urban development (NEPUD). The NEPUD signals the growing centrality of carbon control in discourses, strategies and struggles around urban development. Using examples from cities in the US and Europe, the paper examines how these new environmental policy considerations are being mainstreamed in urban development politics. Alongside competitiveness, the management of carbon emissions represents a new yet at the same time contestable mode of calculation in urban governance. PMID- 22081835 TI - The politics of urban informality in Philadelphia's recovery house movement. AB - There are some 60,000 vacant properties in the city of Philadelphia, 30,000 of which are abandoned row houses. In the neighbourhood of Kensington, street-level entrepreneurs have reconfigured hundreds of former working-class row homes to produce the Philadelphia recovery house movement: an extra-legal poverty survival strategy for addicts and alcoholics located in the city's poorest and most heavily blighted zones. The purpose of this paper is to explore, ethnographically, the ways in which informal poverty survival mechanisms articulate with the restructuring of the contemporary welfare state and the broader political economy of Philadelphia. It is argued that recovery house networks accommodate an interrelated set of political rationalities animated not only by retrenchment and the churning of welfare bodies, but also by the agency of informal operators and the politics of self-help. Working as an alternative and partially vestigial boundary institution or buffer zone to formal regimes of governance, the recovery house movement reflects the 'other story' of the new urban politics in Philadelphia. PMID- 22081836 TI - The neoliberal state and the penalization of misery. AB - The strategy adopted by the neoliberal state to maintain social order and safeguard private property in a context of economic deregulation and social precariousness has destroyed the welfare state and aggravated poverty, depriving the masses of any form of social protection while subjecting them to repression. The reinforcement of the repressive state apparatus is associated with the social instability provoked by the lack of social policies, the degradation of living conditions for the great majority of the population, and the amplification of income and property inequalities both in the so-called capitalist periphery and in the richest industrialized countries. The penalization of misery is revealed as a new expression of class domination. PMID- 22081837 TI - The evolution of human warfare. AB - Here we propose a new theory for the origins and evolution of human warfare as a complex social phenomenon involving several behavioral traits, including aggression, risk taking, male bonding, ingroup altruism, outgroup xenophobia, dominance and subordination, and territoriality, all of which are encoded in the human genome. Among the family of great apes only chimpanzees and humans engage in war; consequently, warfare emerged in their immediate common ancestor that lived in patrilocal groups who fought one another for females. The reasons for warfare changed when the common ancestor females began to immigrate into the groups of their choice, and again, during the agricultural revolution. PMID- 22081838 TI - In the hunt for the "sultans of smack:" dope, gangsters and the construction of the Turkish deep state. AB - This article traces the development and evolution of the Turkish heroin trade against the backdrop of the Republic of Turkey's long transition from imperial core to nation-state. In taking up heroin's relationship to modern Turkey, I would like to specifically explore the meaning and manifestations of what many inside and outside of academia have called the "deep state." Heroin, I argue, was and is one of the most vital enablers of the factional "deep state" rivalries that compete for power in Ankara, adding a steady violent dimension to local and national politics. PMID- 22081840 TI - Student perspective on the future of veterinary education. PMID- 22081839 TI - Prescription pattern of oral healthcare professionals in the use of anticonvulsants for trigeminal neuralgia. AB - OBJECTIVE: The purpose of this study was to investigate the current prescription pattern of oral healthcare professionals in the management of patients with trigeminal neuralgia at a local hospital. STUDY DESIGN: Data relating to a consecutive series of patients (n = 49) with typical trigeminal neuralgia was collected over a period of 6 months. RESULTS: Over half the subjects (70%) were using carbamazepine as the only form of medical therapy. Gabapentin was used in 20% of the subjects. A combination therapy or Topiramate was used in few of the patients in the study group (7.5%). CONCLUSION: Carbamazepine is still the main drug of choice in the management of trigeminal neuralgia. New anti-epileptic drugs have broadened the therapeutic options in those who cannot tolerate conventional carbamazepine therapy or surgical treatment. PMID- 22081841 TI - More thoughts on low-cost vaccination clinics. PMID- 22081842 TI - One health, veterinary public health, and demand for food from animal sources. PMID- 22081843 TI - Additional thoughts on changing veterinary education. PMID- 22081844 TI - The organizing of psychoanalysis in Britain. PMID- 22081845 TI - We (not-so) happy few: symbolic loss and mourning in Freud's psychoanalytic movement and the history of psychoanalysis. PMID- 22081846 TI - "You know that our old institute was entirely destroyed": on the history of the Frankfurt Psychoanalytical Institute (FPI), 1929-1933. PMID- 22081847 TI - [From the history of the agrarian landscape to rural history: the vital scientific heredity of Emilio Sereni]. PMID- 22081848 TI - [The daily functioning of justice in the late Middle Ages: account books as sources for criminal history]. PMID- 22081849 TI - [Eugenics in Argentina, 1890-1940]. PMID- 22081850 TI - [Silver mining and metallurgy in 17th-century New Spain]. PMID- 22081851 TI - [A quantitative analysis of the demand for fertilizer in Jiangnan during the Ming and Qing dynasties]. PMID- 22081852 TI - [Prevalence of conducting mammography tests in women obtained from population surveys: uses and limitations]. PMID- 22081853 TI - [Geographic and socio-economic aspects of access to mammography in Brazil, 2003 2008--interpretive comments]. PMID- 22081854 TI - Basic science and rotator cuff repair: where have we arrived? PMID- 22081855 TI - [Liver, pancreas, biliary tract cancer-2011 update]. PMID- 22081856 TI - [New pathological classification of pancreatic cancer-WHO 2010-]. PMID- 22081857 TI - [Progression of diagnostic technic for pancreas cancer]. PMID- 22081858 TI - Fusion gene vectors allowing for simultaneous drug selection, cell labeling, and reporter assay in vitro and in vivo. AB - Vector systems allowing simultaneously for rapid drug selection, cell labeling, and reporter assay are highly desirable in biomedical research including stem cell biology. Here, we present such a vector system including pCVpf or pCVpr, plasmids that express pf or pr, a fusion protein between puromycin acetyltransferase and green or red fluorescent protein from CV, the human cytomegalovirus enhancer/promoter. Transfection with pCVpf or pCVpr produced a ~10% efficiency of gene transfer. A 2-day pulse puromycin selection resulted in ~13-fold enrichment for transgenic cells, and continuous puromycin selection produced stable transgenic stem cell clones with retained pluripotency. Furthermore, we developed a PAC assay protocol for quantification of transgene expression. To test the usefulness for cell labeling and PAC assay in vivo, we constructed pVASpf containing pf linked to the regulatory sequence of medaka germ gene vasa and generated transgenic fish with visible GFP expression in germ cells. PAC assay revealed the highest expression in the testis. Interestingly, PAC activity was also detectable in somatic organs including the eye, which was validated by fluorescence in situ hybridization. Therefore, the pf and pr vectors provide a useful system for simultaneous drug selection, live labeling, and reporter assay in vitro and in vivo. PMID- 22081859 TI - Multiwalled carbon nanotubes induce a fibrogenic response by stimulating reactive oxygen species production, activating NF-kappaB signaling, and promoting fibroblast-to-myofibroblast transformation. AB - Carbon nanotubes (CNTs) are novel materials with unique electronic and mechanical properties. The extremely small size, fiberlike shape, large surface area, and unique surface chemistry render their distinctive chemical and physical characteristics and raise potential hazards to humans. Several reports have shown that pulmonary exposure to CNTs caused inflammation and lung fibrosis in rodents. The molecular mechanisms that govern CNT lung toxicity remain largely unaddressed. Here, we report that multiwalled carbon nanotubes (MWCNTs) have potent, dose-dependent toxicity on cultured human lung cells (BEAS-2B, A549, and WI38-VA13). Mechanistic analyses were carried out at subtoxic doses (<=20 MUg/mL, <= 24 h). MWCNTs induced substantial ROS production and mitochondrial damage, implicating oxidative stress in cellular damage by MWCNT. MWCNTs activated the NF kappaB signaling pathway in macrophages (RAW264.7) to increase the secretion of a panel of cytokines and chemokines (TNFalpha, IL-1beta, IL-6, IL-10, and MCP1) that promote inflammation. Activation of NF-kappaB involved rapid degradation of IkappaBalpha, nuclear accumulation of NF-kappaBp65, binding of NF-kappaB to specific DNA-binding sequences, and transactivation of target gene promoters. Finally, MWCNTs induced the production of profibrogenic growth factors TGFbeta1 and PDGF from macrophages that function as paracrine signals to promote the transformation of lung fibroblasts (WI38-VA13) into myofibroblasts, a key step in the development of fibrosis. Our results revealed that MWCNTs elicit multiple and intertwining signaling events involving oxidative damage, inflammatory cytokine production, and myofibroblast transformation, which potentially underlie the toxicity and fibrosis in human lungs by MWCNTs. PMID- 22081861 TI - Influence of surface temperature on the mechanism of atomic layer deposition of aluminum oxide using an oxygen plasma and ozone. AB - We have examined the role of substrate temperature on the surface reaction mechanisms during the atomic layer deposition (ALD) of Al(2)O(3) from trimethyl aluminum (TMA) in combination with an O(2) plasma and O(3) over a substrate temperature range of 70-200 degrees C. The ligand-exchange reactions were investigated using in situ attenuated total reflection Fourier transform infrared spectroscopy. Consistent with our previous work on ALD of Al(2)O(3) from an O(2) plasma and O(3) [Rai, V. R.; Vandalon, V.; Agarwal, S. Langmuir 2010, 26, 13732], both -OH groups and carbonates were the chemisorption sites for TMA over the entire temperature range explored. The concentration of surface -CH(3) groups after the TMA cycle was, however, strongly dependent on the surface temperature and the type of oxidizer, which in turn influenced the corresponding growth per cycle. The combustion of surface -CH(3) ligands was not complete at 70 degrees C during O(3) exposure, indicating that an O(2) plasma is a relatively stronger oxidizing agent. Further, in O(3)-assisted ALD, the ratio of mono- and bidentate carbonates on the surface after O(3) exposure was dependent on the substrate temperature. PMID- 22081860 TI - Fruit and vegetable and fried food consumption and 3-(2-deoxy-beta-D-erythro pentafuranosyl)pyrimido[1,2-alpha] purin-10(3H)-one deoxyguanosine adduct formation. AB - Diet has been shown to modulate M(1)dG adduct, a biomarker of oxidative stress and lipid peroxidation. Thus, we analysed the association between diet and M(1)dG in 120 controls and 67 Map Ta Phut industrial estate workers in Rayong, Thailand, to evaluate the influence of fruit and vegetables, and fried and charcoal grilled/barbecued food consumption on M(1)dG. M(1)dG was decreased in controls reporting to consume 14-17 servings/week of fruit and vegetables (mean ratio [MR]= 0.35, CI 0.18-0.69, p< 0.05). Conversely, a non-statistically significant M(1)dG increment was detected in controls consuming 9-18 servings/week of fried food (MR = 1.33, CI 0.88-2.00, p = 0.168). No effect of charcoal grilled/barbecued food was found. No effect of diet was observed in workers. An association with smoking was observed in controls (MR = 1.88, CI 1.14-3.10, p < 0.05), but not in workers. M(1)dG can induce mutations and/or methylation changes within the promoter regions of cancer-related genes, thus promotion of healthy eating practices should be recommended. PMID- 22081862 TI - Cross-cultural comparison of ADHD symptoms among Japanese and US university students. AB - Problems related to attention, hyperactivity, and impulsiveness are known to impact social, academic, and vocational success. When the problems begin in childhood and lead to impaired functioning, the syndrome is identified as attention-deficit/hyperactivity disorder (ADHD). Symptoms of the syndrome persist into adolescence and adulthood for many individuals, but less is known about characteristics of adults compared to children, especially adults attending university. Furthermore, there is little cross-national and cross-cultural research. This study compared DSM-IV-TR ADHD symptoms of US university students (N=271) to Japanese peers (N=712). Comparison of group means on a DSM-IV-TR-based checklist indicated that Japanese students reported more problems with inattention (and overall ADHD symptoms) but not hyperactive-impulsive symptoms. Although differences were statistically significant, effect sizes were small, indicating that for practical purposes, the students reported similar levels of symptoms. Japanese students reported higher rates of meeting or exceeding symptom counts that comprise diagnostic criteria for ADHD, but differences were quite small. Using DSM-IV-TR thresholds, 5.70% of US students and 6.27% of Japanese students reported enough symptoms to meet the cut-off for inattentive, hyperactive/impulsive, or combined type during childhood. With regard to recent problems, 2.66% of US students and 4.52% of Japanese students reported enough symptoms to meet the cut-off for one of the three subtypes. Comparisons using other methods of calculating rates are also provided. This research adds to the limited knowledge of ADHD symptoms in university students across countries and it supports the view that ADHD is not merely a cultural construct. This study is among the first to identify potential attention problems in Japanese university students. PMID- 22081864 TI - Editorial comment to inhibition of cortactin and SIRT1 expression attenuates migration and invasion of prostate cancer DU145 cells. PMID- 22081863 TI - Empirically derived subtypes of lifetime anxiety disorders: developmental and clinical correlates in U.S. adolescents. AB - OBJECTIVE: The current study examined the sex- and age-specific structure and comorbidity of lifetime anxiety disorders among U.S. adolescents. METHOD: The sample consisted of 2,539 adolescents (1,505 females and 1,034 males) from the National Comorbidity Survey-Adolescent Supplement who met criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev. [DSM-IV-TR]) lifetime anxiety disorders (American Psychiatric Association, 2000). Adolescents ranged in age from 13 to 18 years (M = 15.2 years, SE = 0.08 years) and were 39% non-White. Multiple-group latent class analysis was conducted by adolescent sex and age to identify subgroups of adolescents with similar anxiety disorder profiles. Developmental and clinical correlates of empirically derived classes were also examined to assess the nomological validity of identified subgroups. RESULTS: A 7-class solution provided the best fit to the data, with classes defined primarily by one rather than multiple anxiety disorders. Results also indicated that classes displayed similar diagnostic profiles across age, but varied by sex. Classes characterized by multiple anxiety disorders were consistently associated with a greater degree of persistence, clinical severity, impairment, and comorbidity with other DSM-IV-TR psychiatric disorders. CONCLUSIONS: The presentation of lifetime anxiety disorders among adolescents and the observation of unique correlates of specific classes provide initial evidence for the utility of individual DSM-IV-TR anxiety disorder categories. Although findings of the present study should be considered preliminary, results emphasize the potential value of early intervention and gender-specific conceptualization and treatment of anxiety disorders. PMID- 22081865 TI - Motives and decision making of potential living liver donors: comparisons between gender, relationships and ambivalence. AB - The motives and decision making of potential living liver donors are critical areas for transplant clinicians evaluating these candidates to understand, yet these topics remain relatively unstudied. Thus, we surveyed 77 prospective living liver donors at the point of donation evaluation using structured instruments to gather more information on their approach to and concerns about donation. We collected information on donation decision making, motives for donation and anticipated social and physical concerns about postdonation outcomes. We examined three additional characteristics of donors: gender, the relationship of the donor to the intended recipient and the presence of ambivalence about donation. Women had more concerns about their family/social responsibilities. Those donating to nonimmediate family were more likely to have been asked to donate but less likely to feel they had to donate. However, ambivalent donors were the most distinct having difficulties and concerns across most areas from their motivations for donating, to deciding to be tested and to donate, to concerns about the postdonation outcomes. We discuss the clinical relevance of these findings to donor evaluation and preparation. PMID- 22081866 TI - Mixed competition-predation: potential vs. realized interactions. AB - 1. Life-history omnivory or size-induced mixed competition-predation systems have under many conditions theoretically been shown to be fragile, whereas at the same time existing empirical data suggest such systems to be common in nature. 2. In a whole lake experiment covering 17 years, we analysed the effects of the introduction of the intraguild prey roach (Rutilus rutilus) on the population size and individual performance of the intraguild predator perch (Perca fluviatilis) and on resource levels in two low productivity systems. 3. A strong long-term effect of roach on the zooplankton resource but not on the macroinvertebrate resource was present. Competitive effects of roach on perch were observed in one of the lakes the first years after the introduction, but at the end of the study no competitive effect of roach on either size class of perch was observed in any of the two lakes. In contrast, a positive predatory effect reflected in improved growth rates of older perch was present. 4. The lack of a support for a competitive effect of roach on small perch raises the question of the importance of mixed competition-predation interactions in life-history omnivorous systems and the problem of comparing descriptive data on feeding relationships with theoretical predictions based on interaction modules. PMID- 22081867 TI - Monitoring of HIV type 1 DNA load and drug resistance in peripheral blood mononuclear cells during suppressive antiretroviral therapy does not predict virologic failure. AB - Our objective was to determine whether monitoring HIV-1 DNA concentration or new resistance mutations in peripheral blood mononuclear cells (PBMCs) during effective antiretroviral therapy (ART) predicts virologic failure. A retrospective analysis used blood specimens and clinical data from three nevirapine containing arms of a four-arm, open-label, randomized trial comparing ART regimens in HIV-1-infected children who had failed mono- or dual-nucleoside therapy. Sensitive assays compared cell-associated HIV-1 DNA concentrations and nevirapine (NVP) and lamivudine (3TC) resistance mutations in children with plasma HIV-1 RNA <400 copies(c)/ml who did or did not experience subsequent virologic failure. Forty-six children were analyzed through the last available follow-up specimen, collected at 48 (n=16) or 96 (n=30) weeks of ART. Thirty-five (76%) had sustained viral suppression and 11 (24%) had plasma viral rebound to >= 400 c/ml (virologic failure detected at a median of 36 weeks). HIV-1 DNA levels at baseline, 24, 48, and 96 weeks of ART were similar in children who did vs. did not experience virologic failure (p=0.82). HIV-1 DNA levels did not increase prior to viral rebound. NVP resistance mutations were detected in 91% of subjects in the failure group vs. 3% in the suppressed group (p <0.0001). Among nine evaluable children, NVP mutations were first detected prior to virologic failure in two (22%), at viral rebound in five (56%), and after failure in two (22%) children. HIV-1 DNA concentrations did not predict virologic failure in this cohort. New drug resistance mutations were detected in the PBMCs of a minority of virologically suppressed children who subsequently failed ART. PMID- 22081868 TI - Using a nurse invented T-Bar device in a rehabilitation program improved the range of motion for rotator cuff repair patients. AB - AIMS AND OBJECTIVES: This study investigates the effects on patient outcomes of using a T-bar in rehabilitation programs in shoulder arthroscopic surgical procedure patients. BACKGROUND: Orthopaedic nurses play an important role in facilitating restoration of patients' range of motion shoulder function. Conventionally, nurses instruct patients to use the unaffected arm to hold the surgical arm when performing range of motion. However, patients often have difficulty performing the entire range of motion efficiently in this manner. Therefore, nurses have invented a T-bar device to help patients perform range of motion in a rehabilitation program. DESIGN: A repeated-measure, quasi experimental study. METHOD: Sixty-eight participants were recruited from four orthopaedic wards of a medical center in Taipei, Taiwan. Of the patients meeting the inclusion criteria for the study, 33 were assigned to the experimental group and 35 to the comparison group. Both groups had the same shoulder rehabilitation program including identical activities, duration and frequency, except that the experimental group used the nurse invented T-bar device to facilitate range of motion while the comparison group used a conventional method. Data were collected when patients were admitted, five days and four weeks after the surgery. Outcome indicators were shoulder range of motion, muscle power and the American Shoulder and Elbow Society Shoulder Index. Statistical methods used for analysis included mean, standard deviation and repeated measures anova. RESULTS: All the participants completed the study. Results showed a significant improvement in shoulder abduction after surgery in experimental group versus the comparison group. No significant differences were found in other outcomes. CONCLUSIONS: The nurse invented T-bar device used in the rehabilitation program was effective in helping restore the abduction function of rotator cuff repair patients in our preliminary study. RELEVANCE TO CLINICAL PRACTICE: Using a T-bar in the rehabilitation program to improve range of motion may be considered for patients with shoulder surgery. PMID- 22081869 TI - Safer sex as the bolder choice: testosterone is positively correlated with safer sex behaviorally relevant attitudes in young men. AB - INTRODUCTION: Higher testosterone (T) is tied to risk-taking, especially in financial domains but also in health domains relevant to acquiring sexually transmitted infections (STIs). However, safer sex constructs could themselves carry the possibility of "social risk" due to sexual stigma or embarrassment, or could involve boldness or confidence because they could represent status displays of frequent sexual activity. AIM: To determine how T and behaviorally relevant attitudes about sexual risk-taking are linked, to better understand biopsychosocial aspects of sexual health related to STIs. METHODS: In 78 first year male college students, we examined correlations between salivary T and behaviorally relevant safer sex attitudes assessed via questionnaires. MAIN OUTCOME MEASURES: T, via saliva; safer sex attitudes, via a composite and the University of California, Los Angeles Multidimensional Condom Attitudes Scale (MCAS). RESULTS: Higher T was significantly correlated with higher scores on the following: safer sex likelihood composite, r(73)=0.33, P=0.003; the MCAS safer sex resilience, r(32)=0.36, P=0.037; and the MCAS condom purchase comfort, r(32)=0.37, P=0.031. Associations between T and safer sex likelihood and resilience were still robust after controlling for potential confounds, though the association between T and purchase comfort diminished to a trend. CONCLUSIONS: Higher T was positively linked with safer sex attitudes, especially those most closely tied to STI risk avoidance. Thus, future research and interventions for STI prevention should address the possibility that safer sex may be paradoxically perceived as a "bold" or "risky" choice even as it decreases STI risk. PMID- 22081871 TI - Association of smoking with wound complications after cesarean delivery. AB - OBJECTIVE: To determine whether smoking is an independent risk factor for wound dehiscence after cesarean delivery. METHODS: In this case-control study, medical records were reviewed for all patients with wound dehiscence after cesarean delivery during a 7-month period. Wound dehiscence was defined as separation of wound edges requiring treatment. Three control patients without such complications were randomly selected for each case patient. Univariate associations were assessed using t test or Fisher's exact test; univariate odds ratios (OR) and 95% confidence intervals (CI) were calculated with logistic regression. Multivariate associations were assessed with logistic regression on variables with a univariate association significant at p <= 0.10. RESULTS: Of 597 cesarean deliveries, 30 cases (5 %) with wound dehiscence were identified. As individual variables, smoking (46.7 vs. 21.1%, p < 0.01, cases vs. controls), histological chorioamnionitis (27.6 vs. 6.7%, p < 0.01) and preoperative hematocrit (34.0 +/- 3.2 vs. 35.4 +/- 3.4, p < 0.05) were significantly associated with wound complications. In a multivariate logistic regression model, only smoking (OR 5.32; 95% CI 1.77-15.97, p < 0.01) and histological chorioamnionitis (OR 5.62; 95% CI 1.43-22.11, p < 0.01) were independently associated with wound dehiscence. CONCLUSIONS: Smoking and histological chorioamnionitis are independently associated with wound dehiscence after cesarean delivery. PMID- 22081870 TI - Distribution of HPV genotypes in cervical intraepithelial lesions and cervical cancer in Tanzanian women. AB - BACKGROUND: Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection. RESULTS: 79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases. CONCLUSIONS: In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes. PMID- 22081872 TI - Fabrication of all-inorganic nanocrystal solids through matrix encapsulation of nanocrystal arrays. AB - A general strategy for low-temperature processing of colloidal nanocrystals into all-inorganic films is reported. The present methodology goes beyond the traditional ligand-interlinking scheme and relies on encapsulation of morphologically defined nanocrystal arrays into a matrix of a wide-band gap semiconductor, which preserves optoelectronic properties of individual nanoparticles while rendering the nanocrystal film photoconductive. Fabricated solids exhibit excellent thermal stability, which is attributed to the heteroepitaxial structure of nanocrystal-matrix interfaces, and show compelling light-harvesting performance in prototype solar cells. PMID- 22081873 TI - The effect of cocoa supplementation on hepatic steatosis, reactive oxygen species and LFABP in a rat model of NASH. AB - BACKGROUND: Non alcoholic steatohepatitis is hypothesised to develop via a mechanism involving fat accumulation and oxidative stress. The current study aimed to investigate if an increase in oxidative stress was associated with changes in the expression of liver fatty acid binding protein in a rat model of non alcoholic steatohepatitis and whether cocoa supplementation attenuated those changes. METHODS: Female Sprague Dawley rats were fed a high fat control diet, a high fat methionine choline deficient diet, or one of four 12.5% cocoa supplementation regimes in combination with the high fat methionine choline deficient diet. RESULTS: Liver fatty acid binding protein mRNA and protein levels were reduced in the liver of animals with fatty liver disease when compared to controls. Increased hepatic fat content was accompanied by higher levels of oxidative stress in animals with fatty liver disease when compared to controls. An inverse association was found between the levels of hepatic liver fatty acid binding protein and the level of hepatic oxidative stress in fatty liver disease. Elevated NADPH oxidase protein levels were detected in the liver of animals with increased severity in inflammation and fibrosis. Cocoa supplementation was associated with partial attenuation of these pathological changes, although the severity of liver disease induced by the methionine choline deficient diet prevented complete reversal of any disease associated changes. Red blood cell glutathione was increased by cocoa supplementation, whereas liver glutathione was reduced by cocoa compared to methionine choline deficient diet fed animals. CONCLUSION: These findings suggest a potential role for liver fatty acid binding protein and NADPH oxidase in the development of non alcoholic steatohepatitis. Furthermore, cocoa supplementation may have be of therapeutic benefit in less sever forms of NASH. PMID- 22081875 TI - Collateral nervous damages after cryoballoon pulmonary vein isolation. AB - INTRODUCTION: Various types of complications have been reported after atrial fibrillation (AF) ablation using radiofrequency energy, but those have not been well defined when using cryoballoon ablation technique. The objective of this prospective study was to assess types, incidence, and outcome of complications after cryoballoon pulmonary vein isolation (PVI). METHODS AND RESULTS: This prospective monocentric study included 66 consecutive patients (39 males, age 57 +/- 11 years) who underwent cryoballoon PVI for symptomatic paroxysmal AF. Phrenic nerve (PN) integrity was assessed by pacing from the superior vena cava during isolation of the right PVs. Before discharge, all patients were subjected to 24-hour Holter electrocardiograms, echocardiography, and esophagogastroduodenoscopy. Cardiac MRI was scheduled between 1 and 3 months postprocedure. At 3.7 +/- 1.7 months after ablation, patients underwent clinical review and 24-hour Holter electrocardiograms. The mean number of cryoballoon applications was 10.0 +/- 2.1 per patient and 2.5 +/- 1.0 per vein. A 28 mm cryoballoon was used in 49 patients (74%) and a 23 mm cryoballoon in the remaining 17 patients (26%). Twelve complications (18%) attributing to collateral nervous damage were noticed in 9 patients: asymptomatic gastroparesis was observed in 6 patients (9%), transient PN palsy (PNP) in 5 (8%), and symptomatic inappropriate sinus tachycardia requiring beta-blocker treatment in 1 (1%). Neither cryoballoon-related esophageal ulceration nor PV stenosis was observed. CONCLUSION: Gastroparesis and PNP could be observed in a significant number of cases after cryoballoon ablation of AF. These complications are likely due to cryo-induced damages to nervous structures surrounding the heart. PMID- 22081876 TI - A taboo within a stigma? a qualitative study of managing incontinence with people with dementia living at home. AB - BACKGROUND: Incontinence in people with dementia is one of the factors associated with the decision to move to a care home. Managing incontinence adds to carer burden and has been reported by family carers as more difficult to manage than behavioural symptoms. Active management strategies have been reported to be associated with less carer depression. The purpose of this study was to investigate carers' perceptions of the range of incontinence problems they helped their relative with and the strategies they employed to manage these. METHODS: Family carers of people with dementia living in their own homes were recruited through primary care, specialist community mental health services and voluntary organisations. Qualitative semi structured interviews were conducted either face to face or by telephone and thematically analysed. RESULTS: Thirty two carers were interviewed. They described a range of problems from supporting the person to remain independent in toileting, through to dealing with inappropriate behaviours, to containing and managing incontinence. All carers actively used problem solving strategies but sometimes these were not acceptable or understood by the person with dementia, particularly as the dementia progressed. Most carers reported protecting the person's dignity by not seeking health professionals help often until the point of a crisis. Once the carer has decided to seek help the responses from health professionals can be less than helpful, and carers report local health service policies on access to continence products to be inconsistent and often inappropriate to their circumstances. A few carers reported strategies for managing toileting and incontinence that have the potential for distress and harm to the person with dementia. CONCLUSIONS: Primary care professionals could be more proactive in enquiry, repeated over time, about toileting and incontinence problems and in giving advice and information to reduce crisis and problems. PMID- 22081874 TI - Antinociceptive and anti-exudative synergism between dexketoprofen and tramadol in a model of inflammatory pain in mice. AB - Preclinical studies have demonstrated antinociceptive synergism between dexketoprofen (DEX) and tramadol (TRM) in acute animal models of nociception. The aim of the present study was to investigate the type of interaction between DEX and TRM in a chronic musculoskeletal pain model in mice, which fairly replicates the characteristics of chronic osteoarticular pain in humans. Inflammation was induced by a subplantar injection of complete Freund's adjuvant (CFA) in male CF1 mice. Nociceptive thresholds were evaluated using the hot plate, the nocifensive spontaneous behavior and the acetone tests, while plasma extravasation (PE) was assessed with Evan's blue. We used the following experimental groups: control (no inflammation), acute (1 day after CFA injection), and chronic inflammation (7 days after CFA). Dose-response curves for DEX and TRM, individually and combined in a 1 : 1 proportion based on their potency were obtained, and the doses that produced a 50% inhibition calculated. The isobolographic analysis revealed that in all groups of study (no inflammation, acute, and chronic inflammation), the combination of DEX : TRM was synergistic, for both the inhibition of nociception and the PE. The results suggest that the DEX : TRM (1 : 1) combination could be useful in the management of acute and chronic inflammatory musculoskeletal pains in humans; in addition, the synergistic interaction between the drugs observed both during acute and chronic inflammation suggests that less doses would be required of each drug to obtain effective analgesia. PMID- 22081877 TI - Norwegian mastitis control programme. AB - This paper describes the methods and results of the Norwegian Mastitis Control Program implemented in 1982. The program has formed an integral part of the Norwegian Cattle Health Services (NCHS) since 1995. The NCHS also have specific programs for milk fever, ketosis, reproduction and calf diseases. The goal of the program is to improve udder health by keeping the bulk milk somatic cell count (BMSCC) low, to reduce the use of antibiotics, to keep the cost of mastitis low at herd level and improve the consumers' attitude to milk products. In 1996, a decision was made to reduce the use of antibiotics in all animal production enterprises in Norway by 25% within five years. Relevant data has been collected through the Norwegian Cattle Herd Recording System (NCHRS); including health records since 1975 and somatic cell count (SCC) data since 1980. These data have been integrated within the NCHRS. Since 2000, mastitis laboratory data have also been included in the NCHRS. Data on clinical disease, SCC and mastitis bacteriology have been presented to farmers and advisors in monthly health periodicals since 1996, and on the internet since 2005. In 1996, Norwegian recommendations on the treatment of mastitis were implemented. Optimal milking protocols and milking machine function have been emphasised and less emphasis has been placed on dry cow therapy. A selective dry cow therapy program (SDCTP) was implemented in 2006, and is still being implemented in new areas. Research demonstrates that the rate of clinical mastitis could be reduced by 15% after implementing SDCTP. The results so far show a 60% reduction in the clinical treatment of mastitis between 1994 and 2007, a reduction in BMSCC from 250,000 cells/ml to 114,000 cells/ml, and a total reduction in the mastitis cost from 0.23 NOK to 0.13 NOK per litre of milk delivered to the processors, corresponding to a fall from 9.2% to 1.7% of the milk price, respectively. This reduction is attributed to changes in attitude and breeding, eradicating bovine virus diarrhoea virus (BVDV) and a better implementation of mastitis prevention programmes. PMID- 22081878 TI - Smoking abstinence and depressive symptoms modulate the executive control system during emotional information processing. AB - Smoking abstinence disrupts affective and cognitive processes. In this study, functional magnetic resonance imaging (fMRI) was used to investigate the effects of smoking abstinence on emotional information processing. Smokers (n = 17) and non-smokers (n = 18) underwent fMRI while performing an emotional distractor oddball task in which rare targets were presented following negative and neutral task-irrelevant distractors. Smokers completed two sessions: once following 24 hour abstinence and once while satiated. The abstinent versus satiated states were compared by evaluating responses to distractor images and to targets following each distractor valence within frontal executive and limbic brain regions. Regression analyses were done to investigate whether self-reported negative affect influences brain response to images and targets. Exploratory regression analyses examined relations between baseline depressive symptoms and smoking state on brain function. Smoking state affected response to target detection in the right inferior frontal gyrus (IFG). During satiety, activation was greater in response to targets following negative versus neutral distractors; following abstinence, the reverse was observed. Withdrawal-related negative affect was associated with right insula activation to negative images. Finally, depression symptoms were associated with abstinence-induced hypoactive response to negative emotional distractors and task-relevant targets following negative distractors in frontal brain regions. Neural processes related to novelty detection/attention in the right IFG may be disrupted by smoking abstinence and negative stimuli. Reactivity to emotional stimuli and the interfering effects on cognition are moderated by the magnitude of smoking state-dependent negative affect and baseline depressive symptoms. PMID- 22081879 TI - Decision making in children and adolescents: impaired Iowa Gambling Task performance in early adolescence. AB - Disadvantageous decision making is cited as one of the premier problems in childhood development, underlying risky behavior and causing adolescents to make poor choices that could prove detrimental later in life. However, there are relatively few studies looking at the development of decision making in children and adolescents, and fewer still comparing it with the performance trajectories of more typically developing cognitive functions. In the current study, we measured the affective decision-making abilities of children and adolescents 8- to 17-years-old using the Iowa Gambling Task (IGT; Bechara, 2007) in conjunction with a battery of established cognitive neuropsychological assessments. In contrast to the typical linear development of executive functions, affective decision-making abilities progressed in a J-shaped curve. Younger, more developmentally naive children performed better on the IGT than older, early adolescent individuals, with performance becoming advantageous again toward the end of the teenage years. This trajectory is thought to coincide with asymmetric neural development in early adolescents, with relatively overactive striatal regions creating impulsive reward-driven responses that may go unchecked by the slower developing inhibitive frontal cortex. This trajectory is in stark contrast with the linear development of memory, speed of processing, and other cognitive abilities over the ages. PMID- 22081880 TI - Carry on: spontaneous object carrying in 13-month-old crawling and walking infants. AB - Carrying objects requires coordination of manual action and locomotion. This study investigated spontaneous carrying in 24 walkers who were 13 months old and 26 crawlers who were 13 months old during 1-hr, naturalistic observations in the infants' homes. Carrying was more common in walkers, but crawlers also carried objects. Typically, walkers carried objects in their hands, whereas crawlers multitasked by using their hands simultaneously for holding objects and supporting their bodies. Locomotor experience predicted frequency of carrying in both groups, suggesting that experienced crawlers and walkers perceive their increased abilities to handle objects while in motion. Despite additional biomechanical constraints imposed by holding an object, carrying may actually improve upright balance: Crawlers rarely fell while carrying an object, and walkers were more likely to fall without an object in hand than while carrying. Thus, without incurring an additional risk of falling, spontaneous carrying may provide infants with new avenues for combining locomotor and manual skills and for interacting with their environments. PMID- 22081881 TI - Dopaminergic polymorphisms and educational achievement: results from a longitudinal sample of Americans. AB - Although educational attainment has been found to be moderately heritable, research has yet to explore candidate genes for it. Drawing on data from the National Longitudinal Study of Adolescent Health, in the current study, we examined the association between polymorphisms in three dopaminergic genes (DAT1, DRD2, and DRD4), a dopamine index, and educational attainment. Statistically significant effects were found for DAT1, DRD2, DRD4, and the dopamine index for highest level of education. This study is the first to our knowledge that links measured genes to educational attainment. PMID- 22081882 TI - Accurate and simplified consideration of the probe geometrical defaults in scanning electrochemical microscopy: theoretical and experimental investigations. AB - Fabrication of scanning electrochemical microscopy (SECM) tips cannot always guarantee a perfect disk geometry. In the present work, the impact of these defaults is investigated both theoretically and experimentally. The situations where these defaults can accurately be taken into account by considering that the probe behaves like a microdisk with effective geometric parameters are determined. In these situations, the quantitative analysis of the experimental results is greatly simplified. The study also proposes expressions to evaluate the apparent microdisk parameters from a picture of the probe. PMID- 22081883 TI - Calycopterin promotes survival and outgrowth of neuron-like PC12 cells by attenuation of oxidative- and ER-stress-induced apoptosis along with inflammatory response. AB - There is mounting evidence implicating the role of oxidative stress induced by reactive oxygen species (ROS) in neurodegenerative disease, including Alzheimer's disease. Herein we investigated the neuroprotective potential of a natural flavonoid, calycopterin, against H(2)O(2)-induced cell death in differentiated PC12 cells. We pretreated PC12 cells with 25, 50, and 100 MUM calycopterin followed by the addition of H(2)O(2) as an oxidative stress agent. We measured cell viability by the MTT test and found that 50 MUM is the best protective concentration of calycopterin. Moreover, we measured six different parameters of neurite outgrowth. Interestingly, we found that calycopterin not only protects PC12 cells against H(2)O(2)-induced apoptosis but also defends against the destructive effect of oxidative stress on the criteria of neural differentiation. Calycopterin decreased ER stress-associated proteins including calpain and caspase-12, and suppressed ERK, JNK, and p38 MAPK phosphorylation. Moreover, calycopterin inhibited H(2)O(2)-induced nuclear translocation of nuclear factor kappaB, a known regulator of a host of genes involved in specific stress and inflammatory responses. This observation was perfectly in agreement with the decrease of COX-2 and TNF-alpha levels. Calycopterin reduced intracellular ROS levels and increased catalase activity. The protective effect of this compound could represent a promising approach for the treatment of neurodegenerative diseases. PMID- 22081884 TI - Synthesis of aziridines from alkenes and aryl azides with a reusable macrocyclic tetracarbene iron catalyst. AB - A new iron aziridination catalyst supported by a macrocyclic tetracarbene ligand has been synthesized. The catalyst, [((Me,Et)TC(Ph))Fe(NCCH(3))(2)](PF(6))(2), was synthesized from the tetraimidazolium precursor ((Me,Et)TC(Ph))(I)(4) and characterized by NMR spectroscopy, electrospray ionization mass spectrometry, and single-crystal X-ray diffraction. This iron complex catalyzes the aziridination of electron-donating aryl azides and a wide variety of substituted aliphatic alkenes, including tetrasubstituted ones, in a "C(2) + N(1)" addition reaction. Finally, the catalyst can be recovered and reused up to three additional times without significant reduction in yield. PMID- 22081885 TI - Azide functional monolayers grafted to a germanium surface: model substrates for ATR-IR studies of interfacial click reactions. AB - High-quality azide-functional substrates are prepared by a low temperature reaction of 11-bromoundecyltrichlorosilane with UV-ozone-treated germanium ATR-IR plates followed by nucleophilic substitution of the terminal bromine by addition of sodium azide. The resulting monolayer films are characterized by atomic force microscopy (AFM), contact angle analysis, X-ray photoelectron spectroscopy (XPS), attenuated total reflectance infrared spectroscopy (ATR-IR), and ellipsometry. XPS and ellipsometric thickness data correspond well to the results of molecular model calculations confirming the formation of a densely packed azide-functional monolayer. These azide-functional substrates enable interfacial "click" reactions with complementary alkyne-functional molecules to be studied in situ by ATR-IR. To illustrate their potential utility for kinetic studies we show that, in the presence of copper(I) catalyst, the azide-modified surfaces react rapidly and quantitatively with 5-chloro-pentyne to form triazoles via a 1,3-dipolar cycloaddition reaction. Time-resolved ATR-IR measurements indicate that the interfacial click reaction is initially first order in azide concentration as expected from the reaction mechanism, with a rate constant of 0.034 min(-1), and then transitions to apparent second order dependence, with a rate constant of 0.017 min(-1)/(chains/nm(2)), when the surface azide and triazole concentrations become similar, as predicted by Oyama et al. The reaction achieves an ultimate conversion of 50% consistent with the limit expected due to steric hindrance of the 5-chloro-pentyne reactant at the surface. PMID- 22081886 TI - Fouling of nanostructured insect cuticle: adhesion of natural and artificial contaminants. AB - The adhesional properties of contaminating particles of scales of various lengths were investigated for a wide range of micro- and nanostructured insect wing cuticles. The contaminating particles consisted of artificial hydrophilic (silica) and spherical hydrophobic (C(18)) particles, and natural pollen grains. Insect wing cuticle architectures with an open micro-/nanostructure framework demonstrated topographies for minimising solid-solid and solid-liquid contact areas. Such structuring of the wing membranes allows for a variety of removal mechanisms to contend with particle contact, such as wind and self-cleaning droplet interactions. Cuticles exhibiting high contact angles showed considerably lower particle adhesional forces than more hydrophilic insect surfaces. Values as low as 3 nN were recorded in air for silica of ~28 nm in diameter and <25 nN for silica particles 30 MUm in diameter. A similar adhesional trend was also observed for contact with pollen particles. PMID- 22081887 TI - Impaired Pavlovian conditioned inhibition in offenders with personality disorders. AB - Certain types of violent offending are often accompanied by evidence of personality disorders (PDs), a range of heterogeneous conditions characterized by disinhibited behaviours that are generally described as impulsive. The tasks previously used to show impulsivity deficits experimentally (in borderline personality disorder, BPD) have required participants to inhibit previously rewarded responses. To date, no research has examined the inhibition of responding based on Pavlovian stimulus-stimulus contingencies, formally "conditioned inhibition" (CI), in PDs. The present study used a computer-based task to measure excitatory and inhibitory learning within the same CI procedure in offenders recruited from the "personality disorder" and the "dangerous and severe personality disorder" units of a high-security psychiatric hospital. These offenders showed a striking and statistically significant change in the expression of inhibitory learning in a highly controlled procedure: The contextual information provided by conditioned inhibitors had virtually no effect on their prepotent associations. Moreover, this difference was not obviously attributable to nonspecific cognitive or motivational factors. Impaired CI would reduce the ability to learn to control associative triggers and so could provide an explanation of some types of offending behaviour. PMID- 22081889 TI - Maternal red blood cell folate concentration at 10-12 weeks gestation and pregnancy outcome. AB - OBJECTIVE: To determine if maternal circulating red blood cell (RBC) folate concentration in early pregnancy is associated with late gestation pregnancy complications including small for gestational age (SGA) infants, preeclampsia and preterm birth (PTB) in a socioeconomically disadvantaged population. METHOD: This was a retrospective case control study, conducted at Lyell McEwin Health Service, South Australia, including 400 primiparous women. RBC folate and demographic data were collected at 10-12 weeks gestation. Pregnancy outcome data were obtained from patient case notes. RESULTS: Patients who were folate deficient were more likely to develop pregnancy complications, specifically SGA (OR 6.9, 95% CI 2 24.3) and PTB (OR 5.4 95% CI 1.4-21.2). Those who were folate insufficient were also at increased risk of SGA (OR 3.0, 95% CI 1.3-7.7). No association between folate and preeclampsia was found. Women who were supplementing with folic acid delivered infants who were 179 g heavier (5.5% increased birth weight, P = 0.003) and 4.5 days later, compared to those who did not supplement. Furthermore, low RBC folate was associated with cigarette smoking (P < 0.001). CONCLUSIONS: Maternal RBC folate concentration in early pregnancy is associated with SGA and PTB, but not with preeclampsia. PMID- 22081890 TI - Introducing the Geneva Multimodal expression corpus for experimental research on emotion perception. AB - Research on the perception of emotional expressions in faces and voices is exploding in psychology, the neurosciences, and affective computing. This article provides an overview of some of the major emotion expression (EE) corpora currently available for empirical research and introduces a new, dynamic, multimodal corpus of emotion expressions, the Geneva Multimodal Emotion Portrayals Core Set (GEMEP-CS). The design features of the corpus are outlined and justified, and detailed validation data for the core set selection are presented and discussed. Finally, an associated database with microcoded facial, vocal, and body action elements, as well as observer ratings, is introduced. PMID- 22081888 TI - Cu(I)-catalyzed diamination of conjugated dienes. Complementary regioselectivity from two distinct mechanistic pathways involving Cu(II) and Cu(III) species. AB - Conjugated dienes can be diaminated at the internal and/or terminal double bonds using Cu(I) as catalyst and N,N-di-t-butyldiaziridinone (1) as nitrogen source. The regioselectivity is highly dependent upon the choice of Cu(I) catalyst and the substituents on diene substrates. The diamination likely proceeds via two mechanistically distinct pathways. The N-N bond of N,N-di-t-butyldiaziridinone (1) is first homolytically cleaved by the Cu(I) catalyst to form four-membered Cu(III) species A and Cu(II) radical species B, which are in rapid equilibrium. The internal diamination likely proceeds in a concerted manner via Cu(III) species A, and the terminal diamination likely involves Cu(II) radical species B. Kinetic studies have shown that the diamination is first-order in N,N-di-t butyldiaziridinone (1), zero-order in olefin, and first-order in total Cu(I) catalyst, and the cleavage of the N-N bond of 1 by the Cu(I) catalyst is the rate determining step. The internal diamination is favored by use of CuBr without ligand and electron-rich dienes. The terminal diamination is favored when using CuCl-L and dienes with radical-stabilizing groups. PMID- 22081891 TI - Risk factors of pregnancy-related lumbopelvic pain: a biopsychosocial approach. AB - AIMS AND OBJECTIVES: To examine the associations between pain-related psychological and social factors and pregnancy-related lumbopelvic pain intensity and interference after controlling biological factors. BACKGROUND: Pregnancy related lumbopelvic pain is prevalent and has been shown to interfere with women's quality of life. Although pain is a multidimensional phenomenon known to be influenced by psychosocial factors, the majority of previous research on this pregnancy-related lumbopelvic pain has focused on biological factors. DESIGN: Cross-sectional correlational research. METHOD: A sample of 183 pregnant women with lumbopelvic pain was recruited from a medical center in northern Taiwan. Study participants provided demographic information and were administered the Brief Pain Inventory and a modified Catastrophising subscale of the Coping Strategies Questionnaire. Multiple regressions were used to examine the associations among the study variables. RESULTS: Analyses indicated that lower education level was associated with higher pain intensity. Higher pain intensity during pregnancy and catastrophising cognitions were associated significantly with higher pain interference. Moreover, age moderated the strength of the association between pain intensity and pain interference. This association was stronger for older than for younger women. CONCLUSIONS: This study identified the psychosocial factors associated with pregnancy-related lumbopelvic pain intensity (educational level) and interference (pain intensity and catastrophising) and also a variable (age) that moderated the association between pain intensity and pain interference. The findings support a biopsychosocial approach in understanding the experience and impact of pregnancy-related lumbopelvic pain. RELEVANCE TO CLINICAL PRACTICE: Nurses should assess pregnant clients' age, educational level, pain intensity and pain catastrophising thoughts to help identify women who are more at risk for higher lumbopelvic pain intensity or interference. Women endorsing catastrophising cognitions should be referred to or provided with treatment to reduce the frequency of these cognitions that are known to have a negative impact on quality of life in other pain populations. PMID- 22081892 TI - Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. AB - We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming to assign a cause to every failure. We followed 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant. Sixty kidneys progressed to failure in the follow-up period (median 31.4 months). Failure was rare after T-cell-mediated rejection and acute kidney injury and common after antibody-mediated rejection or glomerulonephritis. We developed rules for using biopsy diagnoses, HLA antibody and clinical data to explain each failure. Excluding four with missing information, 56 failures were attributed to four causes: rejection 36 (64%), glomerulonephritis 10 (18%), polyoma virus nephropathy 4 (7%) and intercurrent events 6 (11%). Every rejection loss had evidence of antibody-mediated rejection by the time of failure. Among rejection losses, 17 of 36 (47%) had been independently identified as nonadherent by attending clinicians. Nonadherence was more frequent in patients who progressed to failure (32%) versus those who survived (3%). Pure T-cell-mediated rejection, acute kidney injury, drug toxicity and unexplained progressive fibrosis were not causes of loss. This prospective cohort indicates that many actual failures after indication biopsies manifest phenotypic features of antibody-mediated or mixed rejection and also underscores the major role of nonadherence. PMID- 22081893 TI - Subcutaneous penile insertion of domino fragments by incarcerated males in southwest United States prisons: a report of three cases. AB - INTRODUCTION: Self-insertion of penile foreign bodies is performed worldwide, largely due to a perception that it will enhance sexual performance and virility. There are relatively few cases reported in the United States. AIM: We report three cases of Hispanic men incarcerated in separate southwest United States prisons who utilized a similar technique to insert foreign bodies fabricated out of dominos into the subcutaneous tissues of the penis. METHODS: Details of the three cases were retrospectively reviewed. MAIN OUTCOME MEASURE: Resolution of the case. RESULTS: In each case, an incarcerated Hispanic male or fellow inmate filed a domino into a unique shape for placement under the penile skin. Utilizing the tip of a ballpoint pen or a sharpened shard of plastic to create a puncture wound, each man inserted the domino fragment into the subcutaneous tissue of the penis. All three men presented with infection requiring operative removal. CONCLUSIONS: Incarcerated males put themselves at risk for injury and infection when attempting penile enhancement with improvised equipment. PMID- 22081894 TI - Anti-oxidant defence mechanism in vitiliginous skin increases with skin type. AB - BACKGROUND: Vitiligo skin shows different burning capacity in people with different phototype. In normal skin antioxidant status is correlated to skin phototype, but unexpectedly it appears that there is a gradual decrease in burning susceptibility of depigmented skin of individuals with increasing phototype (II->VI). OBJECTIVE: To assess if the antioxidant response in the lesional vitiligo skin is involved in those protection mechanisms. Moreover, a possible correlation between cutaneous and systemic endogenous antioxidants in vitiligo patients has been investigated. METHODS: We enrolled in the study 29 patients with active vitiligo, divided into five groups according to skin type (II to VI). We analysed reduced and oxidized glutathione (GSH and GSSG, respectively), ubiquinone (CoQ10), catalase (Cat), superoxide dismutases (Cu/Zn SOD and Mn-SOD), GSH peroxidase (GSH-Px), as indexes of chemical and enzymatic antioxidants, in suction blister roofs as well as in peripheral blood mononuclear cells (PBMNCs). RESULTS: The vitiligo patients showed an imbalance of antioxidant network, both in depigmented skin and PBMNCs. Interestingly, in vitiligo skin a phototype-related increase of antioxidant enzyme activities (Cat, Mn-SOD and GPx) and GSH amount have been observed. Similarly in PMBNCs Cat and total SOD activities, as well as GSH content progressively increased from skin type II to skin type VI. Endogenous antioxidants in vitiligo skin are correlated to those in PBMNCs, suggesting that systemic and epidermal antioxidant network functionalities are connected. CONCLUSIONS: The correlation between antioxidant levels and clinical phototype confirmed the hypothesis that other factors than melanin determine largely the minimal erythema dose values in vitiligo lesional skin. PMID- 22081895 TI - Proarrhythmia following prior pulmonary vein isolation: what is the mechanism? PMID- 22081896 TI - A prospective longitudinal study of children's theory of mind and adolescent involvement in bullying. AB - BACKGROUND: Theory of mind (ToM) allows the understanding and prediction of other people's behaviours based on their mental states (e.g. beliefs). It is important for healthy social relationships and thus may contribute towards children's involvement in bullying. The present study investigated whether children involved in bullying during early adolescence had poor ToM in childhood. METHOD: Participants were members of the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative sample of 2,232 children and their families. We visited families when children were 5, 7, 10 and 12 years. ToM was assessed when the children were 5 years using eight standardized tasks. Identification of those children who were involved in bullying as victims, bullies and bully victims using mothers', teachers' and children's reports was carried out when they were 12 years' old. RESULTS: Poor ToM predicted becoming a victim (effect size, d = 0.26), bully (d = 0.25) or bully-victim (d = 0.44) in early adolescence. These associations remained for victims and bully-victims when child specific (e.g. IQ) and family factors (e.g. child maltreatment) were controlled for. Emotional and behavioural problems during middle childhood did not modify the association between poor ToM and adolescent bullying experiences. CONCLUSION: Identifying and supporting children with poor ToM early in life could help reduce their vulnerability for involvement in bullying and thus limit its adverse effects on mental health. PMID- 22081897 TI - Dynamical force and imaging characterization of superhydrophobic surfaces. AB - We devised a dangling cantilever optical lever setup with imaging that permits dynamical studies of superhydrophobic surfaces without the effects of gravitational acceleration for better insight into the mechanics. The setup enabled us to ascertain liquid loss and ascribe it to the interaction of liquid that just touched the superhydrophobic surface as it translated at various constant lateral speeds. At lower speeds (20-60 MUm/s), the interactions were characterized by a strong initial liquid pin (at up to 0.6 nN force) and depin followed by a series of smaller force pin and depins before sufficient liquid loss led to total liquid detachment from the surface. At higher translation speeds (80-100 MUm/s), the interactions were characterized by liquid pinning and depinning processes at a sustained force (around 0.7 nN) in which liquid loss was low enough to engender a much later liquid detachment (beyond 100 s). A linear reduction of the receding contact angle with time, but not with the advancing contact angle, was found up to the point of first liquid depinning. This suggested a stronger role played by the receding contact line in establishing liquid adherence to the superhydrophobic surface. The detachment process from the surface was also characterized by a liquid bridge driven to rupture by way of liquid being conveyed away from the bridge. PMID- 22081899 TI - A model of the cell nucleus for DNA damage calculations. AB - AIMS: Development of a computer model of genomic deoxyribonucleic acid (DNA) in the human cell nucleus for DNA damage and repair calculations. The model comprises the human genomic DNA, chromosomal domains, and loops attached to factories. MATERIAL AND METHODS: A model of canonical B-DNA was used to build the nucleosomes and the 30-nanometer solenoidal chromatin. In turn the chromatin was used to form the loops of factories in chromosome domains. The entire human genome was placed in a spherical nucleus of 10 micrometers diameter. To test the new target model, tracks of protons and alpha-particles were generated using Monte Carlo track structure codes PITS99 (Positive Ion Track Structure) and KURBUC. Damage sites induced in the genome were located and classified according to type and complexity. RESULTS: The three-dimensional structure of the genome starting with a canonical B-DNA model, nucleosomes, and chromatin loops in chromosomal domains are presented. The model was used to obtain frequencies of DNA damage induced by protons and alpha-particles by direct energy deposition, including single- and double-strand breaks, base damage, and clustered lesions. CONCLUSIONS: This three-dimensional model of the genome is the first such model using the full human genome for the next generation of more comprehensive modelling of DNA damage and repair. The model combines simple geometrical structures at the level of domains and factories with potentially full detail at the level of atoms in particular genes, allowing damage patterns in the latter to be simulated. PMID- 22081901 TI - Phytochemical analysis of Plantago sempervirens from Majella National Park. AB - In this study, we report the isolation and identification of several compounds from Plantago sempervirens Crantz, collected in the protected area of Majella National Park. We examined the polar fraction, in particular the iridoidic one. Aucubin, caryoptoside, plantarenaloside and gardoside were isolated and identified. For the first time, in this species, 8-epiloganic acid was recognised. Also, verbascoside, a phenylethanoid glycoside, was recognised in this plant. PMID- 22081903 TI - Acute twin-twin transfusion syndrome in labor: pathophysiology and associated factors. AB - OBJECTIVE: To review reported cases of acute twin-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies to help define variants of disease and determine associated factors. METHODS: PubMed literature review using the search terms, "acute" and "twin transfusion." Articles were reviewed for clinical factors. Reference lists were carefully assessed for any additional articles. In order to rule out sudden progression of chronic TTTS as the cause, gestational age >=31 weeks was chosen. Cases were classified into subsets of acute TTTS. RESULTS: There were 150 publications from 1942-2010. There were 51 cases that were classified into four variants of acute TTTS. Four cases were difficult to classify, with hemoglobin levels that were high normal and low normal, high normal and anemic, or low normal and polycythemic. Three publications defined the incidence for acute perinatal TTTS of 1.8-5.5% of monochorionic twins. Common factors associated with acute perinatal TTTS included monochorionicity and labor. CONCLUSIONS: Monochorionicity and labor are common factors underlying the propensity to acute perinatal TTTS. A spectrum of severity is for acute TTTS was seen. Perinatal specialists and neonatologists should be aware of the possibility of acute TTTS during labor, so rapid volume replacement can be performed for neonatal resuscitation. PMID- 22081904 TI - Rational design of stereoselectivity in the class II pyruvate aldolase BphI. AB - BphI, a pyruvate-specific class II aldolase, catalyzes the reversible carbon carbon bond formation of 4-hydroxy-2-oxoacids up to eight carbons in length. During the aldol addition catalyzed by BphI, the S-configured stereogenic center at C4 is created via attack of a pyruvate enolate intermediate on the si face of the aldehyde carbonyl of acetaldehyde to form 4(S)-hydroxy-2-oxopentanoate. Replacement of a Leu-87 residue within the active site of the enzyme with polar asparagine and bulky tryptophan led to enzymes with no detectable aldolase activity. These variants retained decarboxylase activity for the smaller oxaloacetate substrate, which is not inhibited by excess 4-hydroxy-2 oxopentanoate, confirming the results from molecular modeling that Leu-87 interacts with the C4-methyl of 4(S)-hydroxy-2-oxoacids. Double variants L87N;Y290F and L87W;Y290F were constructed to enable the binding of 4(R)-hydroxy 2-oxoacids by relieving the steric hindrance between the 5-methyl group of these compounds and the hydroxyl substituent on the phenyl ring of Tyr-290. The resultant enzymes were shown to exclusively utilize only 4(R)- and not 4(S) hydroxy-2-oxopentanoate as the substrate. Polarimetric analysis confirmed that the double variants are able to synthesize 4-hydroxy-2-oxoacids up to eight carbons in length, which were the opposite stereoisomer compared to those produced by the wild-type enzyme. Overall the k(cat)/K(m) values for pyruvate and aldehydes in the aldol addition reactions were affected <=10-fold in the double variants relative to the wild-type enzyme. Thus, stereocomplementary class II pyruvate aldolases are now available to create chiral 4-hydroxy-2-oxoacid skeletons as synthons for organic reactions. PMID- 22081906 TI - Mastitis diagnostics and performance monitoring: a practical approach. AB - In this paper a review is given of frequently used mastitis diagnostic methods in modern dairy practice. Methods used at the quarter, cow, herd and regional or national level are discussed, including their usability for performance monitoring in udder health. Future developments, such as systems in which milk derived parameters are combined with modern analytical techniques, are discussed. It is concluded that, although much knowledge is available and science is still developing and much knowledge is available, it is not always fully exploited in practice. PMID- 22081907 TI - Cytomegalovirus-specific regulatory and effector T cells share TCR clonality- possible relation to repetitive CMV infections. AB - Cytomegalovirus (CMV) infections have a major impact on morbidity and mortality of transplant patients. Among the complex antiviral T-cell response, CMV-IE-1 antigen-specific CD8+ cells are crucial for preventing CMV disease but do not protect from recurring/lasting CMV reactivation. Recently, we confirmed that adoptive transfer of autologous IE-1/pp65-specific T-cell lines was able to combat severe CMV disease; however, the control of CMV infection was only temporary. We hypothesized that CMV-induced regulatory T cells (iTreg) might be related to recurring/lasting CMV infection. In fact, kidney transplant patients with recurring CMV infections expressed enhanced suppression on CMV response. Analysis of in vitro expanded CD4+ epitope-specific cells revealed that CMV specific CD4+CD25(high) Treg cells functionally suppress CD25(low) effector T cells (Teff) upon epitope-specific reactivation. Their phenotype is similar to iTreg - CD39(high) /Helios-/IL-2(low) /IFNgamma(high) /IL-10+/-/TGFbeta-LAP+/ /FOXP3+ and methylated foxp3 locus. Remarkably, in vitro expanded CD4+CD25(high) iTreg share the same dominant TCR-Vbeta-CDR3 clones with functionally distinct CD4+CD25(low) Teff. Moreover, the same clones were present in freshly isolated CD4+CD25(high) and CD4+CD25(low) T cells suggesting their in vivo generation. These findings directly demonstrate that Teff and iTreg can differentiate from one "mother" clone with specificity to the same viral epitope and indicate that peripheral iTreg generation is related to frequent antigen appearance. PMID- 22081908 TI - Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report. AB - INTRODUCTION: Paroxysmal nocturnal hemoglobinuria is an acquired disorder of hemopoiesis and is characterized by recurrent episodes of intravascular hemolysis due to an increased sensitivity to complement-mediated hemolysis. Systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. We report a case of paroxysmal nocturnal hemoglobinuria that developed in a patient with systemic lupus erythematosus and lupus nephritis. CASE PRESENTATION: A 29-year old Mongolian woman had systemic lupus erythematosus, which manifested only as skin lesions when she was 12 years old. She had leg edema and proteinuria when she was 23 years old, and a renal biopsy revealed lupus nephritis (World Health Organization type IV). She had been treated with steroids and immunosuppressant therapy. At 29, she had headaches, nausea, general fatigue, and severe pancytopenia and was admitted to our hospital. A laboratory evaluation showed hemolytic anemia. Further examination showed a neutrophil alkaline phosphatase score of 46 points, a CD55 value of 18%, and a CD59 value of 78.6%. The results of Ham test and sugar water tests were positive. The constellation of symptoms throughout the clinical course and the laboratory findings suggested paroxysmal nocturnal hemoglobinuria. CONCLUSIONS: To the best of our knowledge, systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. Clinicians should be aware of the association between autoimmune and hematological diseases. PMID- 22081909 TI - Genetic moderation of contextual effects on negative arousal and parenting in African-American parents. AB - A three-stage context amplification model was tested with a sample of 345 African American parent-child dyads. The model combined the conceptual structure of stress generation with recent findings regarding genetic susceptibility. Because the 7R + allele of the dopamine transporter (DRD4) has the potential to enhance contextual priming and arousal, this allele was examined as a potential moderator of each stage of the amplification process. Particular attention was given to the hypothesized influence of parental negative arousal on valence of parent-child interactions. The literature on genetic susceptibility led to the hypothesis that DRD4 would moderate each stage of the model in a "for better or for worse" manner. The model was partially supported. DRD4 moderated effects at all three stages of the model and, as hypothesized, DRD4 moderated contextual effects on negative arousal in a "for better or for worse" manner. Effects on parent-child interaction, however, were moderated in a "for worse" manner only. These results indicate that parenting interactions may amplify the effects of positive and negative contexts in a stress-generating manner, and that a susceptibility framework captures the way in which DRD4 moderates the impact of context on negative arousal. PMID- 22081910 TI - Family functioning among returnees to Orthodox Judaism in Israel. AB - The role of religious conversion in marriages and family functioning has been little explored. The current study examined family functioning and parenting stress among returnees to Orthodox Judaism with adolescent children. Possible explanatory factors for difficulties, such as attachment insecurity, religious discord in families, and poor community integration, were also explored. Randomly selected samples of returnee and nonreturnee Orthodox Jews with adolescent children (N = 1632) completed measures of attachment, community integration, marital functioning, and parenting stress. Results indicate that returnees report greater family disengagement (lack of warmth), family chaos (lack of control), and parenting stress. They also reported higher religious discord, higher attachment insecurity, and poorer community integration, which all correlated with higher parenting stress, family disengagement (lack of warmth), and family chaos (lack of control). Moreover, differences between returnees and nonreturnees on family functioning and parenting stress were largely mediated by differences in the explanatory factors. These results substantiate previous anecdotal reports and suggest possible avenues for intervention among Orthodox returnees with family difficulties. They also support the relevance of religious factors in family functioning. PMID- 22081911 TI - Symptoms and uncertainty in breast cancer survivors in Korea: differences by treatment trajectory. AB - AIMS: The study compared the levels of symptoms and uncertainty, their associated factors, relationships between them and predictors of uncertainty by treatment trajectory among breast cancer survivors. BACKGROUND: Little is known with regard to how uncertainty and symptoms are related to treatment trajectory among breast cancer survivors. DESIGN: A cross-sectional descriptive design was used. METHOD: A total of 252 women with breast cancer, receiving cancer therapy, or having completed their therapy were recruited from the National Cancer Center in Korea. Measurements used included symptom subscales of the European Organization of Research and Therapy for Cancer QLQ-C30 and Breast Cancer Module BR23 and the Mishel Uncertainty in Illness Scale. RESULTS: Women in treatment reported more severe symptoms and higher levels of uncertainty than women having completed treatment. During treatment, most symptoms were positively correlated with the level of uncertainty, whereas, in women who had completed treatment, only dyspnoea, insomnia, systemic therapy side effects and arm symptoms positively correlated with uncertainty. There were also differences in predictors of uncertainty by treatment trajectory. Age, marital status and pain were significant predictors of uncertainty during treatment, while monthly income, dyspnoea and insomnia were predictors of uncertainty after treatment. CONCLUSIONS: Among breast cancer survivors, levels of symptoms and uncertainty, associated factors, relationships between them and predictors of uncertainty differed depending on treatment trajectory. RELEVANCE TO CLINICAL PRACTICE: To provide trajectory-sensitive nursing intervention for uncertainty among breast cancer survivors, age, marital status and pain should be considered during treatment, while factors such as economic status, dyspnoea and insomnia should be taken into account after treatment. PMID- 22081912 TI - ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. AB - Schistocytes are fragments of red blood cells (RBCs) produced by extrinsic mechanical damage within the circulation. The detection of schistocytes is an important morphological clue to the diagnosis of thrombotic microangiopathic anemia (TMA). Reporting criteria between different laboratories, however, are not uniform, owing to variability of shape and nature of fragments, as well as subjectivity and heterogeneity in their morphological assessment. Lack of standardization may lead to inconsistency or misdiagnosis, thereby affecting treatment and clinical outcome. The Schistocyte Working Group of the International Council for Standardization in Haematology (ICSH) has prepared specific recommendations to standardize schistocyte identification, enumeration, and reporting. They deal with the type of smear, method of counting, morphological description based on positive criteria (helmet cells, small, irregular triangular, or crescent-shaped cells, pointed projections, and lack of central pallor). A schistocyte count has a definite clinical value for the diagnosis of TMA in the absence of additional severe red cell shape abnormalities, with a confident threshold value of 1%. Automated counting of RBC fragments is also recommended by the ICSH Working Group as a useful complement to the microscope, according to the high predictive value of negative results, but worthy of further research and with limits in quantitation. PMID- 22081914 TI - The role of implantable cardiac electrical devices in patients with myotonic dystrophy. PMID- 22081915 TI - Synthesis of length-controlled polyvalent silver nanowire-DNA conjugates for sensitive and selective detection of DNA targets. AB - We have developed a facile method to rapidly synthesize the monodisperse silver nanowire-DNA conjugates with a constant diameter and systematically controllable lengths in the range of 0.5-2.5 MUm. The synthesis of silver nanowires takes advantage of poly(sodium 4-styrenesulfonate) as a structure-directing reagent and is performed under very mild conditions such as room temperature and aqueous media. The nanowires are densely conjugated with DNA sequences enough to exhibit the cooperative properties for the sensitive and selective detection of DNA targets. The limit of detection is 50 pM. PMID- 22081913 TI - New genes that extend Caenorhabditis elegans' lifespan in response to reproductive signals. AB - In Caenorhabditis elegans and Drosophila, removing germline stem cells increases lifespan. In C. elegans, this lifespan extension requires DAF-16, a FOXO transcription factor, and DAF-12, a nuclear hormone receptor. To better understand the regulatory relationships between DAF-16 and DAF-12, we used microarray analysis to identify downstream genes. We found that these two transcription factors influence the expression of distinct but overlapping sets of genes in response to loss of the germline. In addition, we identified several new genes that are required for loss of the germline to increase lifespan. One, phi-62, encodes a conserved, predicted RNA-binding protein. PHI-62 influences DAF 16-dependent transcription, possibly by collaborating with TCER-1, a putative transcription elongation factor, and FTT-2, a 14-3-3 protein known to bind DAF 16. Three other genes encode proteins involved in lipid metabolism; one is a triacylglycerol lipase, and another is an acyl-CoA reductase. These genes do not noticeably affect bulk fat storage levels; therefore, we propose a model in which they may influence production of a lifespan-extending signal or metabolite. PMID- 22081916 TI - Splanchnic vein thrombosis complicating severe acute pancreatitis. PMID- 22081917 TI - Fast-track programmes for hepatopancreatic resections: where do we stand? AB - BACKGROUND: Fast-track (FT) programmes represent a series of multimodal concepts that may reduce surgical stress and speed up convalescence after surgery. The aim of this systematic review was to evaluate FT programmes for patients undergoing hepatopancreatic surgery. METHODS: PubMed, Embase and the Cochrane Library databases were searched for studies of FT vs. conventional recovery strategies for liver and pancreatic resections. RESULTS: For liver surgery, three cohort studies were included. Primary hospital stay was significantly reduced after FT care in two of the three studies. There were no significant differences in rates of readmission, morbidity and mortality. For pancreatic surgery, three cohort studies and one case-control study were included. Primary hospital stay was significantly shorter after FT care in three out of the four studies. One study reported a significantly decreased readmission rate (7% vs. 25%; P= 0.027), and another study showed lower morbidity (47.2% vs. 58.7%; P < 0.01) in favour of the FT group. There was no difference in mortality between the FT and control groups. CONCLUSIONS: FT rehabilitation for liver and pancreatic surgical patients is feasible. Future investigation should focus on optimizing individual elements of the FT programme within the context of liver and pancreatic surgery. PMID- 22081918 TI - Natural history of pancreatitis-induced splenic vein thrombosis: a systematic review and meta-analysis of its incidence and rate of gastrointestinal bleeding. AB - BACKGROUND: Pancreatitis-induced splenic vein thrombosis (PISVT) is an acquired anatomic abnormality that impacts decision making in pancreatic surgery. Despite this influence, its incidence and the rate of associated gastrointestinal (GI) bleeding are imprecisely known. METHODS: The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to June 2010 for abstracts documenting PISVT in acute (AP) or chronic pancreatitis (CP). Two reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% confidence intervals. RESULTS: After review of 241 abstracts, 47 studies and 52 case reports were graded as relevant. These represent a cohort of 805 patients with PISVT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidences of PISVT of 14.1% in all patients, 22.6% in patients with AP and 12.4% in patients with CP. The incidence of associated splenomegaly was only 51.9% in these patients. Varices were identified in 53.0% of patients and were gastric in 77.3% of cases. The overall rate of GI bleeding was 12.3%. CONCLUSIONS: Although reported incidences of PISVT vary widely across studies, an overall incidence of 14.1% is reported. Splenomegaly is an unreliable sign of PISVT. Although the true natural history of PISVT remains unknown, the collective reported rate of associated GI bleeding is 12.3%. PMID- 22081920 TI - Splanchnic vein thrombosis in severe acute pancreatitis: a 2-year, single institution experience. AB - OBJECTIVES: This study aimed to determine current practice in the management and outcome of splanchnic vein thrombosis complicating acute pancreatitis (AP). METHODS: An audit of prospectively collected data for all patients presenting with AP was conducted. Patients with splanchnic vein thrombosis were grouped according to vessel involvement and whether or not systemic anticoagulation was administered. RESULTS: Of 127 consecutive patients admitted with AP, 20 had splanchnic venous thrombosis; in all cases the thrombosis was associated with a severe attack of AP. Involvement of the splenic vein (SV), portal vein (PV) and superior mesenteric vein (SMV) was observed in 14, 10 and three patients, respectively. Involvement of more than one vessel was observed in six patients (SV and PV in four patients; SMV and SV in one patient; all three veins in one patient). Thromboses were colocalized with collections in 19 patients. Only four patients received systemic anticoagulation. Resolution of thrombosis was observed in six patients over a median of 77 days. No significant differences were observed in recanalization rates following anticoagulation (P= 0.076). No complications associated with systemic anticoagulation occurred. One patient developed liver failure associated with progressive PV thrombosis and one patient died. CONCLUSIONS: Splanchnic vein thrombosis is a relatively common observation in severe AP and is associated with pancreatic necrosis and peripancreatic collections. Recanalization is observed in almost a third of patients, irrespective of whether or not they receive systemic anticoagulation. PMID- 22081919 TI - Metabolic syndrome and hepatic resection: improving outcome. AB - OBJECTIVE: A review of the peri-operative risk associated with hepatic resection in patients with metabolic syndrome (MetS) and identification of measures for the improvement of cardiometabolic disturbances and liver-related mortality. BACKGROUND: MetS and its hepatic manifestation non-alcoholic fatty liver disease (NAFLD) are associated with an increased operative mortality in spite of a significant improvement in peri-operative outcome after hepatic resection. METHODS: A review of the English literature on MetS, liver resection and steatosis was performed from 1980 to 2011 using the MEDLINE and PubMed databases. RESULTS: MetS is a predictor of NAFLD and patients with multiple metabolic risk factors may harbour non-alcoholic steatohepatitis (NASH) predictive of operative and cardiovascular mortality. Pre-operative diagnosis of unsuspected NASH with the selective use of a liver biopsy can modify the operative strategy by limiting the extent of hepatic resection, avoiding or altering the pre-operative chemotherapy regimen and the utilization of portal vein embolization. Thiazolidinediones are therapeutic for MetS and NASH and Vitamin E for active NASH; however, their utility in improving the peri-operative outcome after hepatic resection is unknown. A short-term regimen for weight loss improves post operative patient and liver-related outcomes in patients with >30% steatosis. Cardiovascular disease associated with MetS or NAFLD should be managed aggressively. Peri-operative measures to minimize thrombotic events and acute renal injury secondary to the pro-inflammatory, prothrombotic state of MetS may further improve the outcome. CONCLUSION: Potential candidates for hepatic resection should be screened for MetS as the pre-operative identification of NASH, short-term treatment of significant steatosis, cardiovascular risk assessment and optimization of each component of MetS may improve the peri operative outcome in this high-risk subset of patients. PMID- 22081921 TI - High-grade dysplasia of the cystic duct margin in the absence of malignancy after cholecystectomy. AB - BACKGROUND: A total of 750,000 cholecystectomies are performed annually in the USA. No data exist on patients with microscopic high-grade dysplasia at the cystic duct margin and the associated incidence of cholangiocarcinoma. METHODS: Pathology reports for 1992-2010 were reviewed for patients with high-grade dysplasia of the cystic duct margin in the absence of invasive gallbladder cancer. Clinical data were obtained from chart review. RESULTS: Five patients with high-grade dysplasia at the cystic duct margin without evidence of malignancy were identified. Radiologic imaging was abnormal in two patients. The cystic duct stump was abnormally dilated in both patients and one patient had an enlarged portacaval lymph node. All five patients underwent exploration and resection of either the cystic duct stump or the bile duct. Specimens in four of the patients showed no evidence of malignancy or dysplasia. One patient was found to have a node-positive adenocarcinoma of the cystic duct. CONCLUSIONS: High grade dysplasia at the cystic duct margin without evidence of invasive gallbladder cancer is rare. Patients with this finding should undergo cross sectional imaging and a diagnosis of an underlying cholangiocarcinoma should be considered, especially if imaging reveals any abnormalities. PMID- 22081922 TI - Factors associated with recidivism following pancreaticoduodenectomy. AB - OBJECTIVES: Factors related to readmission after pancreaticoduodenectomy (PD) may include postoperative morbidity and the functional status of the patient. This study aimed to retrospectively review our institution's experience of readmission of patients who had undergone Whipple procedure PD. METHODS: Recidivism was defined as readmission to the primary or a secondary hospital within, respectively, 30 days, 30-90 days or 90 days postoperatively. Associations between recidivism, perioperative factors and patient characteristics were evaluated. RESULTS: During the past 5 years, 30-day, 30-90-day and 90-day recidivism rates were 14.5%, 18.5% and 27.4%, respectively. The most common reasons for readmission included dehydration and/or malnutrition (37.5% of readmissions) and pain (12.5%). Patients who underwent PD for chronic pancreatitis were more likely to be readmitted within 90 days of surgery than patients who underwent PD for malignancy (P < 0.01). Intraoperative transfusion was also associated with 30-90-day and 90-day recidivism (P < 0.01). Preoperative comorbidities, including Charlson Comorbidity Index score, number of pre discharge complications, type of Whipple reconstruction, preoperative biliary stenting, need for vascular reconstruction and patient body mass index were not associated with recidivism. CONCLUSIONS: Our data confirm previous reports indicating high rates of readmission after PD. To our knowledge, this report is the first to demonstrate chronic pancreatitis as an independent risk factor for readmission. PMID- 22081923 TI - Conditional survival in pancreatic cancer: better than expected. AB - BACKGROUND: Traditional survival estimates after resection for pancreatic cancer are based on clinicopathological variables at the time of diagnosis. Estimates have not reflected time survived after resection, as investigated for other malignancies. The aim of the present study was to understand how survival estimates change after pancreatic resection for cancer based on time already survived (conditional survival). METHODS: Pancreatectomies performed for pancreatic ductal adenocarcinoma (PDAC) between 2001 and 2010 were reviewed. Clinicopathological variables were evaluated to identify predictors of survival. Expected survival according to a validated nomogram for pancreatic cancer as well as conditional survival estimates and actual survival were calculated. RESULTS: In all, 186 patients underwent pancreatic resection for PDAC [154 (82.8%) Whipple, 26 (14.0%) distal and 6 (3.2%) total]. Median (range) survival was 22 (3.4-107.3) months. Predictors of overall survival were: absence of nodal disease [odds ratio (OR) 8.8], age <67 years (OR 8.4) and lower stage (OR 4.3). Expected survival according to the nomogram was 70% (1 year), 39.5% (2 years) and 24% (3 years). As time passed, and overall and expected survival decreased, conditional survival increased. DISCUSSION: The available prognostic system for PDAC underestimated survival compared with actual survival in the present study. Conditional survival estimates, based on accrued lifespan, were better than either predicted or actual survival, suggesting that survival is a dynamic, rather than static, concept. Conditional survival may, therefore, be a useful tool to allow patients and clinicians to project subsequent survival based on time accrued since resection. PMID- 22081924 TI - Metastatic lymph nodes in hilar cholangiocarcinoma: does size matter? AB - AIM: To determine the diagnostic efficacy of the size criteria for the detection of metastatic lymph nodes (LN) in patients with hilar cholangiocarcinoma (HCCA). INTRODUCTION: LN metastasis is one of the most significant independent prognostic factors in patients with HCCA. Presently, in spite of the well known lack of sensitivity and specificity, one of the most used clinical criteria for nodal metastases is LN size. METHODS: Pathological slides of 147 patients who had undergone exploration for HCCA were assessed. The size (maximum and short axis diameter) of each single node was retrieved from the pathology report or measured from a section on the glass slide using a stereo microscope and a calibrated ruler integrated in the software. When a metastatic lesion was detected, the proportion of the lesion in relation to LN size was estimated. RESULTS: Out of 147 patients, 645 LN were retrieved and measured. In all, 106 nodes (16%) showed evidence of metastasis. The proportion of positive nodes was 8% in nodes <5 mm and 37% in nodes >30 mm. Ten per cent of LN smaller than 10 mm were positive, whereas only 23% of LN larger than 10 mm were metastastically involved. No clear cut-off point could be found. Similar results were found for the short axis diameter. In 50% of positive LN, the metastatic lesion accounted for 10% or less of the LN size. CONCLUSION: No cut-off point could be determined for accurately predicting nodal involvement. Therefore, imaging studies should not rely on LN size when assessing nodal involvement. PMID- 22081925 TI - Pre- and intraoperative variables affecting early outcomes in elderly patients undergoing pancreaticoduodenectomy. AB - BACKGROUND: Conflicting data exist regarding the safety of pancreatic resections in elderly patients. In this study we compared early complication and mortality rates between patients younger and older than 80 years of age who underwent pancreaticoduodenectomy using a validated national database. METHODS: The National Surgical Quality Improvement Program (NSQIP) database for 2005-2009 was used for this retrospective analysis. The primary outcome measures for our analysis were 30-day postoperative mortality, major complication rate and overall complication rate. RESULTS: A total of 6293 patients who underwent PD for any cause were included in the analysis. Of these, 9.4% were aged >=80 years. The incidence of 30-day mortality was significantly higher in patients aged >=80 years (6.3%) than in those aged <80 years (2.7%). Older patients were also noted to have higher rates of overall complications and serious complications. On multivariate analysis, age, ASA (American Society of Anesthesiologists) classification, reduced functional status, history of dyspnoea, and need for intraoperative transfusion were risk factors associated with the occurrence of overall complications, serious complications and postoperative mortality. CONCLUSIONS: This study shows that age among other factors is a determinant of postoperative morbidity and mortality following PD. PMID- 22081926 TI - Management of excluded bile ducts in paediatric orthotopic liver transplant recipients of technical variant allografts. AB - BACKGROUND: A strategy to increase the number of size- and weight-appropriate organs and decrease the paediatric waiting list mortality is wider application of sectional orthotopic liver transplantation (OLT). These technical variants consist of living donor, deceased donor reduced and split allografts. However, these grafts have an increased risk of biliary complications. An unusual and complex biliary complication which can lead to graft loss is inadvertent exclusion of a major segmental bile duct. We present four cases and describe an algorithm to correct these complications. METHODS: A retrospective review of the paediatric orthotopic liver transplantation database (2000-2010) at Washington University in St. Louis/St. Louis Children's Hospital was conducted. RESULTS: Sixty-eight patients (55%) received technical variant allografts. Four complications of excluded segmental bile ducts were identified. Percutaneous cholangiography provided diagnostic confirmation and stabilization with external biliary drainage. All patients required interval surgical revision of their hepaticojejunostomy for definitive drainage. Indwelling biliary stents aided intra-operative localization of the excluded ducts. All allografts were salvaged. DISCUSSION: Aggressive diagnosis, percutaneous decompression and interval revision hepaticojejunostomy are the main tenets of management of an excluded bile duct. Careful revision hepaticojejunostomy over a percutaneous biliary stent can result in restoration of biliary continuity and allograft survival. PMID- 22081927 TI - Endovascular stent graft placement in the treatment of a ruptured tuberculous pseudoaneurysm of the descending thoracic aorta secondary to Pott's disease of the spine. AB - Ruptured thoracic aortic tuberculous pseudoaneurysms as a complication of mycobacterium tuberculosis infection of the spine are rare. Conventional treatment of a ruptured tuberculous pseudoaneurysm involves surgery with graft interposition or patch repair. We report successful repair of a ruptured tuberculous pseudoaneurysm of the descending thoracic aorta by endovascular stent graft placement and provide a literature review of such entities. PMID- 22081928 TI - Editorial: seeking a new characterisation of learning disorders. PMID- 22081930 TI - Human papillomavirus genotype distribution in Madrid and correlation with cytological data. AB - BACKGROUND: Cervical cancer is the second most common cancer in women worldwide. Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor associated with cervical cancer. This study analysed the distribution of type-specific HPV infection among women with normal and abnormal cytology, to assess the potential benefit of prophylaxis with anti-HPV vaccines. METHODS: Cervical samples of 2,461 women (median age 34 years; range 15-75) from the centre of Spain were tested for HPV DNA. These included 1,656 samples with normal cytology (NC), 336 with atypical squamous cells of undetermined significance (ASCUS), 387 low-grade squamous intraepithelial lesions (LSILs), and 82 high grade squamous intraepithelial lesions (HSILs). HPV detection and genotyping were performed by PCR using 5'-biotinylated MY09/11 consensus primers, and reverse dot blot hybridisation. RESULTS: HPV infection was detected in 1,062 women (43.2%). Out of these, 334 (31%) samples had normal cytology and 728 (69%) showed some cytological abnormality: 284 (27%) ASCUS, 365 (34%) LSILs, and 79 (8%) HSILs. The most common genotype found was HPV 16 (28%) with the following distribution: 21% in NC samples, 31% in ASCUS, 26% in LSILs, and 51% in HSILs. HPV 53 was the second most frequent (16%): 16% in NC, 16% in ASCUS, 19% in LSILs, and 5% in HSILs. The third genotype was HPV 31 (12%): 10% in NC, 11% in ASCUS, 14% in LSILs, and 11% in HSILs. Co-infections were found in 366 samples (34%). In 25%, 36%, 45% and 20% of samples with NC, ASCUS, LSIL and HSIL, respectively, more than one genotype was found. CONCLUSIONS: HPV 16 was the most frequent genotype in our area, followed by HPV 53 and 31, with a low prevalence of HPV 18 even in HSILs. The frequency of genotypes 16, 52 and 58 increased significantly from ASCUS to HSILs. Although a vaccine against HPV 16 and 18 could theoretically prevent approximately 50% of HSILs, genotypes not covered by the vaccine are frequent in our population. Knowledge of the epidemiological distribution is necessary to predict the effect of vaccines on incidence of infection and evaluate cross-protection from current vaccines against infection with other types. PMID- 22081931 TI - Depression among carers of AIDS-orphaned and other-orphaned children in Umlazi Township, South Africa. AB - South Africa faces the challenge of supporting the well-being of adults caring for growing numbers of AIDS-orphaned children. These adults play a critical role in responses to the epidemic, but little information exists in regard to their mental health needs. This paper reports on findings from n=1599 adults, recruited through representative household sampling, who serve as primary carers for children in Umlazi Township, an HIV-endemic community. Overall, 22% of participants were carers of AIDS-orphaned children, 11% were carers of other orphaned children and 67% were carers of non-orphaned children. Prevalence of depression was 30.3%. Orphan carers, regardless of whether they cared for AIDS orphaned or other-orphaned children, were significantly more likely than carers of non-orphaned children to meet the clinical threshold for depression (35.2% vs. 27.9%, p < 0.01). In multivariate logistic regressions, food insecurity and being a female carer were identified as additional risk factors for greater depression. In contrast, households with access to running water and households dependent on salaries as the main source of income were identified as protective factors for disparities in depression. Mental health interventions are urgently needed to address an increased risk for depression among all orphan carers, not just those caring for AIDS-orphaned children. PMID- 22081932 TI - Synthesis, characterization and biological evaluation of ureidofibrate-like derivatives endowed with peroxisome proliferator-activated receptor activity. AB - A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. A calorimetric approach was used to characterize PPARgamma-ligand interactions, and docking experiments and X-ray studies were performed to explain the observed potency and efficacy. R-1 and S-1 were selected to evaluate several aspects of their biological activity. In an adipogenic assay, both enantiomers increased the expression of PPARgamma target genes and promoted the differentiation of 3T3-L1 fibroblasts to adipocytes. In vivo administration of these compounds to insulin resistant C57Bl/6J mice fed a high fat diet reduced visceral fat content and body weight. Examination of different metabolic parameters showed that R-1 and S-1 are insulin sensitizers. Notably, they also enhanced the expression of hepatic PPARalpha target genes indicating that their in vivo effects stemmed from an activation of both PPARalpha and gamma. Finally, the capability of R-1 and S-1 to inhibit cellular proliferation in colon cancer cell lines was also evaluated. PMID- 22081933 TI - A funny thing happened to me on the way to the universe: a Dread-Pirate-Roberts job? PMID- 22081934 TI - MCP-1 and CCR2 gene variants and the risk for osteoporosis and osteopenia. AB - AIM: In this study, we investigated whether monocyte chemotactic protein 1 (MCP 1) and CC chemokine receptor 2 (CCR2) gene polymorphisms account for an increased risk of osteoporosis or osteopenia. METHODS: Three hundred three postmenopausal women, 80 osteoporotic, 123 osteopenic, and 100 unrelated age-matched healthy controls, were included in the study. Genotyping of MCP-1 A2518G and CCR2 V64I gene polymorphisms were detected by PCR-RFLP. RESULTS: We, for the first time, demonstrated the positive association of MCP-1 GG, CCR2 Val/Ile, and CCR2 Val+ genotype with osteoporosis risk. However, CCR2 Ile/Ile genotype frequencies were high in the control group compared with those of the patients with osteoporosis and osteopenia. Haplotype analysis confirmed the association of MCP-1/CCR2 gene variants with osteopenia and revealed that the frequency of MCP-1 A:CCR2 Val haplotype was significantly higher in patients when compared with controls. CONCLUSIONS: In conclusion, our findings have suggested that MCP-1 and CCR2 gene variants were risk factors for osteoporosis and osteopenia. PMID- 22081935 TI - Proteomic analysis of secretagogue-stimulated neutrophils implicates a role for actin and actin-interacting proteins in Rac2-mediated granule exocytosis. AB - BACKGROUND: Neutrophils are abundant leukocytes that play a primary role in defence against pathogens. Neutrophils enter sites of infection where they eliminate pathogens via phagocytosis and the release of antimicrobial mediators via degranulation. Rho GTPases, particularly Rac2, play a key role in neutrophil degranulation. The purpose of this study was to identify Rac2-dependent changes in protein abundance in stimulated neutrophils. METHODS: We performed a proteomic analysis on secretagogue-stimulated bone marrow neutrophils that were isolated from wild-type and Rac2-/- mice. Protein abundance was analyzed by 2-dimensional SDS-PAGE of fluorescently labelled samples which allowed the detection ~3500 proteins. RESULTS: We identified 22 proteins that showed significant changes in abundance after secretagogue-stimulation of wild-type neutrophils, which did not occur in neutrophils isolated from Rac2-/- mice. As expected, the abundance of several granule proteins was reduced in wild-type cells; this did not occur in Rac2-/- neutrophils which confirms the requirement for Rac2 in degranulation. We also found changes in abundance of many actin remodelling proteins including coronin-1A, beta-actin and the F-actin capping protein, (CapZ-beta). Coronin-1A showed elevated levels of several isoforms after stimulation of neutrophils from wild-type, but not from Rac2-/- mice. These isoforms were immunoreactive with anti-phospho-threonine antibodies, suggesting that neutrophil stimulation triggers a Rac2-dependent kinase cascade that results in the phosphorylation of coronin-1A. CONCLUSION: The control of Rac2-mediated degranulation in neutrophils likely functions through actin remodelling via activation of several actin binding proteins. We found coronin-1A to be a novel downstream effector protein of this pathway that is threonine phosphorylated in response to secretagogue stimulation. PMID- 22081936 TI - Excessive gestational weight gain predicts large for gestational age neonates independent of maternal body mass index. AB - OBJECTIVE: To determine the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on large-for-gestational-age (LGA) birth weight (>=90th % ile). METHODS: We examined 4321 mother-infant pairs from the Ottawa and Kingston (OaK) birth cohort. Multivariate logistic regression (controlling for gestational and maternal age, pre-pregnancy weight, parity, smoking) were performed and odds ratios (ORs) calculated. RESULTS: Prior to pregnancy, a total of 23.7% of women were overweight and 16.2% obese. Only 29.3% of women met GWG targets recommended by the Institute of Medicine (IOM), whereas 57.7% exceeded the guidelines. Adjusting for smoking, parity, age, maternal height, and achieving the IOM's recommended GWG, overweight (OR 1.99; 95%CI 1.17 3.37) or obese (OR 2.64; 95% CI 1.59-4.39) pre-pregnancy was associated with a higher rate of LGA compared to women with normal BMI. In the same model, exceeding GWG guidelines was associated with higher rates of LGA (OR 2.86; 95% CI 2.09-3.92), as was parity (OR 1.49; 95% CI 1.22-1.82). Smoking (OR 0.53; 95%CI 0.35-0.79) was associated with decreased rates of LGA. The adjusted association with LGA was also estimated for women who exceeded the GWG guidelines and were overweight (OR 3.59; 95% CI 2.60-4.95) or obese (OR 6.71; 95% CI 4.83-9.31). CONCLUSION: Pregravid overweight or obesity and gaining in excess of the IOM 2009 GWG guidelines strongly increase a woman's chance of having a larger baby. Lifestyle interventions that aim to optimize GWG by incorporating healthy eating and exercise strategies during pregnancy should be investigated to determine their effects on LGA neonates and down-stream child obesity. PMID- 22081937 TI - Probing a complex of cytochrome c and cardiolipin by magnetic circular dichroism spectroscopy: implications for the initial events in apoptosis. AB - Oxidation of cardiolipin (CL) by its complex with cytochrome c (cyt c) plays a crucial role in triggering apoptosis. Through a combination of magnetic circular dichroism spectroscopy and potentiometric titrations, we show that both the ferric and ferrous forms of the heme group of a CL:cyt c complex exist as multiple conformers at a physiologically relevant pH of 7.4. For the ferric state, these conformers are His/Lys- and His/OH(-)-ligated. The ferrous state is predominantly high-spin and, most likely, His/-. Interconversion of the ferric and ferrous conformers is described by a single midpoint potential of -80 +/- 9 mV vs SHE. These results suggest that CL oxidation in mitochondria could occur by the reaction of molecular oxygen with the ferrous CL:cyt c complex in addition to the well-described reaction of peroxides with the ferric form. PMID- 22081938 TI - Does oral health matter in people's daily life? Oral health-related quality of life in adults 35-47 years of age in Norway. AB - OBJECTIVE: The aim of this study was to assess the effect of oral health on aspects of daily life measured by the Dental Impact Profile (DIP) in 35- to 47 year-old individuals in Norway, and to study associations between reported effects and demographic variables, subjectively assessed oral health, general health, oral health behaviour and clinical oral health. MATERIAL AND METHODS: A stratified randomized sample of 249 individuals received a questionnaire regarding demographic questions, dental visits, oral hygiene behaviour, self rated oral health and general health and satisfaction with oral health. The DIP measured the effects of oral health on daily life. Teeth present and caries experience were registered by clinical examination. Bi- and multivariate analyses and factor analysis were used. RESULTS: Items most frequently reported to be positively or negatively influenced by oral health were chewing and biting, eating, smiling and laughing, feeling comfortable and appearance. Only 1% reported no effects of oral health. Individuals with fewer than two decayed teeth, individuals who rated their oral health as good or practised good oral health habits reported more positive effects than others on oral quality of life (P <= 0.05). When the variables were included in multivariate analysis, none was statistically significant. The subscales of the DIP were somewhat different from the originally suggested subscales. CONCLUSIONS: This study showed that most adults reported oral health to be important for masticatory functions and confirmed that oral health also had impacts on other aspects of life. PMID- 22081939 TI - Treatment of mastitis during lactation. AB - Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials. PMID- 22081940 TI - The costs of repression: a meta-analysis on the relation between repressive coping and somatic diseases. AB - OBJECTIVE: When Freud introduced the term repression, he stated its pathogenic potential. Since then, this notion was adapted and continued to date. Surprisingly, there is no attempt to synthesize research on the effect of repressive coping on somatic diseases quantitatively. The current study closes this gap and examines the association between repressive coping as operationalized by Weinberger, Schwartz, and Davidson (1979) and the incidence of cancer, cardiovascular diseases, asthma, and diabetes by applying meta-analytic techniques. METHOD: An extensive literature search identified 22 studies that met all inclusion criteria and assessed a total of 6,775 participants. The study set was analyzed both as a whole sample (k = 22 studies) and disease-specific (k = 2 10 studies; no study found for diabetes). RESULTS: The results of the meta analysis indicate a higher risk for repressive copers to suffer from one of the investigated diseases, especially cancer (logOdds after diagnosis: 0.41; 95% confidence interval, 0.09-0.73, p = .012) and hypertension (logOdds: 0.59; 95% confidence interval, 0.32-0.86, p < .0001). After application of a continuity correction due to a missing control group the results for coronary heart disease imply an increased risk for nonrepressors to be affected. Results for cardiovascular diseases in general, heart attack, and asthma did not reach significance. CONCLUSIONS: The current meta-analysis revealed significant associations between repressive coping, cancer, and cardiovascular diseases, especially hypertension. These results add to the notion of repressive coping as a consequence of cancer as well as to its important role for the issue of hypertension. PMID- 22081941 TI - Knowing loved ones' end-of-life health care wishes: attachment security predicts caregivers' accuracy. AB - OBJECTIVE: At times, caregivers make life-and-death decisions for loved ones. Yet very little is known about the factors that make caregivers more or less accurate as surrogate decision makers for their loved ones. Previous research suggests that in low stress situations, individuals with high attachment-related anxiety are attentive to their relationship partners' wishes and concerns, but get overwhelmed by stressful situations. Individuals with high attachment-related avoidance are likely to avoid intimacy and stressful situations altogether. We hypothesized that both of these insecure attachment patterns limit surrogates' ability to process distressing information and should therefore be associated with lower accuracy in the stressful task of predicting their loved ones' end-of life health care wishes. METHOD: Older patients visiting a medical clinic stated their preferences toward end-of-life health care in different health contexts, and surrogate decision makers independently predicted those preferences. For comparison purposes, surrogates also predicted patients' perceptions of everyday living conditions so that surrogates' accuracy of their loved ones' perceptions in nonstressful situations could be assessed. RESULTS: Surrogates high on either type of insecure attachment dimension were less accurate in predicting their loved ones' end-of-life health care wishes. It is interesting to note that even though surrogates' attachment-related anxiety was associated with lower accuracy of end-of-life health care wishes of their loved ones, it was associated with higher accuracy in the nonstressful task of predicting their loved ones' everyday living conditions. CONCLUSIONS: Attachment orientation plays an important role in accuracy about loved ones' end-of-life health care wishes. Interventions may target emotion regulation strategies associated with insecure attachment orientations. PMID- 22081943 TI - Facile and efficient route to polyimide-TiO2 nanocomposite coating onto carbon fiber. AB - Polyamic acid-TiO(2) hybrid colloid emulsion with an average particle size of 200 nm was formed by dispersing nano-TiO(2) into polyamic acid colloidal emulsion. The polyimide-TiO(2) nanocomposite was coated onto carbon fiber by electrophoretic deposition. The primary properties of polyamic acid-TiO(2) hybrid colloid emulsion and polyimide-TiO(2) nanocomposite coating onto carbon fiber were characterized using laser scattering, ZetaPlus particle sizing, transmission electron microscopy, field-emission scanning electron microscope, Fourier transforms infrared spectroscopy, and X-ray Diffraction analysis. The results indicated that the small amount of nano-TiO(2) would be effectively dispersed in polyamic acid colloidal particles. The polyimide-TiO(2) hybrid nanocomposite coating carbon fiber sheet displayed an excellent photodegradation performance of methyl orange, which could be degraded more than 70 wt % after 10 cycles. PMID- 22081942 TI - A comprehensive assessment of mitochondrial protein synthesis and cellular proliferation with age and caloric restriction. AB - It is proposed that caloric restriction (CR) increases mitochondrial biogenesis. However, it is not clear why CR increases an energetically costly biosynthetic process. We hypothesized that 40% CR would decrease mitochondrial protein synthesis and would be regulated by translational rather than transcriptional mechanisms. We assessed cumulative mitochondrial protein synthesis over 6 weeks and its transcriptional and translational regulation in the liver, heart, and skeletal muscle of young (6 month), middle (12 month), and old (24 month) male B6D2F1 mice that were lifelong CR or ad lib (AL) controls. Mitochondrial protein synthesis was not different between AL and CR (fractional synthesis over 6 weeks (range): liver, 91-100%; heart, 74-85%; skeletal muscle, 53-72%) despite a decreased cellular proliferation in liver and heart with CR. With CR, there was an increase in AMP-activated protein kinase phosphorylation/total (P:T) in heart and liver, and an increase in peroxisome proliferator-activated receptor gamma coactivator 1-alpha mRNA in all tissues, but not protein. Ribosomal protein S6 was decreased with CR. In conclusion, CR maintained mitochondrial protein synthesis while decreasing cellular proliferation during a time of energetic stress, which is consistent with the concept that CR increases somatic maintenance. Alternative mechanisms to global translation initiation may be responsible for selective translation of mitochondrial proteins. PMID- 22081944 TI - Synchronous presentation of acute acalculous cholecystitis and appendicitis: a case report. AB - INTRODUCTION: Acute acalculous cholecystitis is traditionally associated with elderly or critically ill patients. CASE PRESENTATION: We present the case of an otherwise healthy 23-year-old Caucasian man who presented with acute right-sided abdominal pain. An ultrasound examination revealed evidence of acute acalculous cholecystitis. A laparoscopy was undertaken and the dual pathologies of acute acalculous cholecystitis and acute appendicitis were discovered and a laparoscopic cholecystectomy and appendectomy were performed. CONCLUSION: Acute acalculous cholecystitis is a rare clinical entity in young, healthy patients and this report describes the unusual association of acute acalculous cholecystitis and appendicitis. A single stage combined laparoscopic appendectomy and cholecystectomy is an effective treatment modality. PMID- 22081945 TI - Breakdown of the integration center: right atrial ganglionated plexus dysfunction in heart failure. PMID- 22081947 TI - Donor cell-derived acute myeloid leukemia after second allogenic cord blood transplantation in a patient with Fanconi anemia. AB - DCL following hematopoietic stem cell transplantation has been reported in approximately 5% of all leukemic relapses. There have been several reports on DCL, mainly AML after umbilical cord blood transplantation. In this case study, we present a young boy diagnosed with Fanconi anemia who underwent an umbilical cord blood transplantation. Because of the graft failure, he was retransplanted one month later, also with a cord blood transplant. Two years after the second transplant, he developed AML, where 100% of the cells were of female donor origin. The donor, a now 14-yr-old female, was recently reported healthy. PMID- 22081946 TI - Furfural reduction mechanism of a zinc-dependent alcohol dehydrogenase from Cupriavidus necator JMP134. AB - FurX is a tetrameric Zn-dependent alcohol dehydrogenase (ADH) from Cupriavidus necator JMP134. The enzyme rapidly reduces furfural with NADH as the reducing power. For the first time among characterized ADHs, the high-resolution structures of all reaction steps were obtained in a time-resolved manner, thereby illustrating the complete catalytic events of NADH-dependent reduction of furfural and the dynamic Zn(2+) coordination among Glu66, water, substrate and product. In the fully closed conformation of the NADH complex, the catalytic turnover proved faster than observed for the partially closed conformation due to an effective proton transfer network. The domain motion triggered by NAD(H) association/dissociation appeared to facilitate dynamic interchanges in Zn(2+) coordination with substrate and product molecules, ultimately increasing the enzymatic turnover rate. NAD(+) dissociation appeared to be a slow process, involving multiple steps in concert with a domain opening and reconfiguration of Glu66. This agrees with the report that the cofactor is not dissociated from FurX during ethanol-dependent reduction of furfural, in which ethanol reduces NAD(+) to NADH that is subsequently used for furfural reduction. PMID- 22081949 TI - Editorial: a new beginning and ending? PMID- 22081948 TI - The experience of empowerment in the patient-staff encounter: the patient's perspective. AB - AIM AND OBJECTIVE: The aim was to explore empowerment within the patient-staff encounter as experienced by out-patients with chronic kidney disease. BACKGROUND: Empowerment has an important role to play in the patient-staff relationship in the case of patients with a chronic disease. When it comes to patients with chronic kidney disease, there has been little research on empowerment, for which reason interviewing such patients about their experiences of empowerment will provide useful knowledge within the context of out-patient care. DESIGN: A qualitative interview study was chosen to gain an understanding of empowerment from the patient perspective. METHOD: The study was carried out at an out-patient clinic in Sweden and involved 20 patients with chronic kidney disease. The interviews were subjected to latent content analysis. RESULTS: Five of the seven sub-themes emerging from the analysis represented empowerment: Accessibility according to need, Confirming encounter, Trust in the competence of the healthcare staff, Participation in decision-making, Learning enables better self management. The other two represented non-empowerment: Meeting with nonchalance, Lack of dialogue and influence. From the seven sub-themes, one comprehensive theme was generated: Creation of trust and learning through encounter. CONCLUSION: The main finding regarding the central role of the creation of trust and learning through the patient-staff encounter underlines the importance of understanding empowerment from the patient's perspective. RELEVANCE TO CLINICAL PRACTICE: Nursing and other healthcare staff need knowledge and understanding of the meaning of empowerment from the patients' perspective to meet their needs in out-patient care. PMID- 22081951 TI - Validation of tool mark analysis of cut costal cartilage. AB - This study was designed to establish the potential error rate associated with the generally accepted method of tool mark analysis of cut marks in costal cartilage. Three knives with different blade types were used to make experimental cut marks in costal cartilage of pigs. Each cut surface was cast, and each cast was examined by three analysts working independently. The presence of striations, regularity of striations, and presence of a primary and secondary striation pattern were recorded for each cast. The distance between each striation was measured. The results showed that striations were not consistently impressed on the cut surface by the blade's cutting edge. Also, blade type classification by the presence or absence of striations led to a 65% misclassification rate. Use of the classification tree and cross-validation methods and inclusion of the mean interstriation distance decreased the error rate to c. 50%. PMID- 22081952 TI - Modes of (in)tolerance: South African Muslims and same-sex relationships. AB - In this study we interviewed members of a small, predominantly Muslim community in Johannesburg, South Africa, in order to ascertain attitudes towards people who engage in same-sex practices. We were interested in ascertaining whether community perceptions of homosexuality match the common (Western) assumption that Islam is profoundly homophobic. Our research, while preliminary, shows that although most people condemn same-sex practices on the grounds of religious principle, they also in practice did not act upon these views. Respondents held different views on whether a person is gay or lesbian as result of same-sex behaviour, on the one hand, or same-sex desire, on the other hand. This distinction accords with what was, for them, the difficulty of proving the same sex practices had occurred given strict Muslim standards of proof. Community attitudes to homosexuality usually involve denial and secrecy in order to maintain the social fabric of daily life and relationships between community members. PMID- 22081954 TI - Global trend in articles related to stereotactic published in science citation index-expanded. AB - BACKGROUND: This is the first article using bibliometrics to study the field of stereotactic related research. This study aims to evaluate the global scientific production of simulation research in the category of "stereotactic" during 1993 2008 and to provide insights on the characteristics of the stereotactic related research patterns, tendencies, and methods that might exist in the papers, as well as in leading countries and institutes. METHODS: In this study, "stereotactic*" was used as the keyword to search titles, abstracts, and keywords in the database of the Science Citation Index Expanded. All the articles referring to stereotactic during the studied years, were assessed by the following aspects: document type of publication, characteristics of publication outputs, distribution of outputs in journals, publication outputs of source country, source institute, and analysis of words cluster in title, author keywords, and KeyWords Plus. RESULTS: Eleven document types were found in the total 10 015 publications during 1993-2008. Clinical neurology was the most common category in stereotactic-related research. Neurosurgery listed in categories of clinical neurology and surgery, ranked first. The most productive country and institute were USA and University of Pittsburgh respectively. Words cluster analysis was elaborated regarding the issues of movement disorders, radiosurgery, tumor, and vascular/stroke, it revealed the sharp rise of articles from 1995 until the end of the period covered in "movement disorders" category. CONCLUSIONS: The results analyzed by this bibliometric method can show the research performance, significant events and major inventors, those attributed to stereotactic neurosurgery, and trend of stereotactic related research. PMID- 22081953 TI - Ozonated autohemotherapy: protection of kidneys from ischemia in rats subjected to unilateral nephrectomy. AB - BACKGROUND: Ozonated autohemotherapy (OA) has been previously successfully used in the treatment of patients affected by peripheral occlusive arterial disease. OA consists of an intrafemoral reinfusion of autologous blood previously exposed to a mixture of oxygen/ozone (O2/O3). This study analyzes the effects of OA in protecting rat kidney from ischemia and ischemia/reperfusion damage. METHODS: We performed OA 30 min before the induction of 60 min renal ischemia or at the induction of 60 min postischemic reperfusion in rats subjected to unilateral nephrectomy. In addition, to evidence the possible protection induced by O2/O3 on endothelial functions, the present study analyzes the in vitro effects of O2/O3 on oxygen consumption by human umbilical vein endothelial cells (HUVEC). RESULTS: 1) OA preserves rat kidney functions and architecture, as demonstrated by the improved levels of serum creatinine and blood urea nitrogen and by histology; 2) such protection does not correlate with the increase of plasmatic nitric oxide, but is compatible with a focal renal increase of renal betaNADPH-diaphorase; 3) treatment of HUVEC with O2/O3 significantly increases both the rate of oxygen consumption and the mitochondrial activity assessed by confocal microscopy. CONCLUSION: The preservation of the mitochondrial activity of endothelium could in vivo limit the endothelial dysfunction provoked by the Isc or Isc/R processes. PMID- 22081955 TI - Multiple cerebral aneurysms secondary to cardiac myxoma. AB - A 45-year-old lady presented with transient ischemic attack symptoms. Subsequent CT and DSA revealed multiple fusiform dilatations of cerebral vessels. A search for sources of emboli led to an atrial myxoma being found on echocardiogram. She made a good recovery after resection of the atrial myxoma. The aneurysms were managed conservatively. We discuss the association of multiple cerebral aneurysms with atrial myxoma. PMID- 22081956 TI - Oxford craniotomy infections database: a cost analysis of craniotomy infection. AB - We describe the process of establishing a large database for the investigation of craniotomy infection and the preliminary results of this database. The initial results have been used to generate a cost analysis for craniotomy infection. The craniotomy infections database prospectively registers craniotomy cases taking place in the John Radcliffe Hospital. In order to achieve this, each patient's details are registered at the time of operation and followed up to identify cases of infection. Infection was defined strictly according to Centre for Disease Control criteria and validated by at least two members of clinical staff. The first 10 months of data are presented here which identifies a total of 245 craniotomies and 20 verified craniotomy infections. An overall infection rate of 8% is identified, and the cost incurred by the neurosurgery department as a result of craniotomy infections is estimated at L1 85 660 for the 10-month period studied. This amounts to a cost per case of infection of L9283. PMID- 22081957 TI - General anxiety, depression, and physical health in relation to symptoms of heart focused anxiety- a cross sectional study among patients living with the risk of serious arrhythmias and sudden cardiac death. AB - OBJECTIVE: To investigate the role of three distinct symptoms of heart-focused anxiety (cardio-protective avoidance, heart-focused attention, and fear about heart sensations) in relation to general anxiety, depression and physical health in patients referred to specialized cardio-genetics outpatient clinics in Norway for genetic investigation and counseling. METHODS: Participants were 126 patients (mean age 45 years, 53.5% women). All patients were at higher risk than the average person for serious arrhythmias and sudden cardiac death (SCD) because of a personal or a family history of an inherited cardiac disorder (familial long QT syndrome or hypertrophic cardiomyopathy). Patients filled in, Hospital Anxiety and Depression Scale, Short-Form 36 Health Survey, and Cardiac Anxiety Questionnaire, two weeks before the scheduled counseling session. RESULTS: The patients experienced higher levels of general anxiety than expected in the general population (mean difference 1.1 (p < 0.01)). Hierarchical regression analyses showed that avoidance and fear was independently related to general anxiety, depression, and physical health beyond relevant demographic covariates (age, gender, having children) and clinical variables (clinical diagnosis, and a recent SCD in the family). In addition to heart-focused anxiety, having a clinical diagnosis was of importance for physical health, whereas a recent SCD in the family was independently related to general anxiety and depression, regardless of disease status. CONCLUSION: Avoidance and fear may be potentially modifiable symptoms. Because these distinct symptoms may have important roles in determining general anxiety, depression and physical health in at-risk individuals of inherited cardiac disorders, the present findings may have implications for the further development of genetic counseling for this patient group. PMID- 22081958 TI - Clinically important drug-drug interactions in primary care. AB - WHAT IS KNOWN AND OBJECTIVE: Drug-drug interactions (DDIs) cause considerable morbidity and mortality worldwide and may lead to hospital admission. Sophisticated computerized drug information and monitoring systems, more recently established in many of the emerging economies, including Malaysia, are capturing useful information on prescribing. Our aim is to report on an investigation of potentially serious DDIs, using a university primary care-based system capturing prescription records from its primary care services. METHODS: We retrospectively collected data from two academic years over 20 months from computerized databases at the Universiti Sains Malaysia (USM) from users of the USM primary care services. RESULTS AND DISCUSSION: Three hundred and eighty-six DDI events were observed in a cohort of 208 exposed patients from a total of 23,733 patients, representing a 2-year period prevalence of 876.4 per 100,000 patients. Of the 208 exposed patients, 138 (66.3%) were exposed to one DDI event, 29 (13.9%) to two DDI events, 15 (7.2%) to three DDI events, 6 (2.9%) to four DDI events and 20 (9.6%) to more than five DDI events. Overall, an increasing mean number of episodes of DDIs was noted among exposed patients within the age category >=70 years (P=0.01), an increasing trend in the number of medications prescribed (P<0.001) and an increasing trend in the number of long-term therapeutic groups (P<0.001). WHAT IS NEW AND CONCLUSION: We describe the prevalence of clinically important DDIs in an emerging economy setting and identify the more common potentially serious DDIs. In line with the observations in developed economies, a higher number of episodes of DDIs were seen in patients aged >=70 years and with more medications prescribed. The easiest method to reduce the frequency of DDIs is to reduce the number of medications prescribed. Therapeutic alternatives should be selected cautiously. PMID- 22081959 TI - Relationship between obesity/overweight status, sugar consumption and dental caries among adolescents in South India. AB - OBJECTIVE: To evaluate the relationship between obesity/overweight status, sugar consumption and dental caries among adolescents in Udupi District, India. METHODS: Study population consisted of 463 school children aged between 13 and 15 years. Information on age, sex, type of school attending and frequency of sugar consumption per day was recorded by a structured self-administered questionnaire. Body mass index (BMI) (height in metres and weight in kilograms) and caries measurements (DMFT) were taken by a trained recorder according to standard criteria. RESULTS: Majority of the children were having low normal weight, with 18.6% in overweight and 3.5% in obese groups. There was a significant difference in the frequency of sugar consumption between the BMI groups. Obese group of children had more caries than the overweight and low-normal-weight children. Correlation analysis showed significant positive relation with BMI, decayed teeth and DMFT. Regression analysis showed that caries experience had a significant association with male sex (OR = 2.09, CI = 1.01-4.33), overweight/obese (OR = 3.68, CI = 1.79-7.56) and frequency of sugar consumption more than once per day (OR = 3.13, CI = 1.25-7.85). CONCLUSION: There was a significant association between overweight/obesity and caries experience among school children of Udupi District. Obesity and dental caries have common risk determinants and require a comprehensive multidisciplinary approach to paediatric patients by both medical and dental healthcare professionals. PMID- 22081960 TI - Crystallographic proof for an extended hydrogen-bonding network in small prolyl isomerases. AB - Parvulins compose a family of small peptidyl-prolyl isomerases (PPIases) involved in protein folding and protein quality control. A number of amino acids in the catalytic cavity are highly conserved, but their precise role within the catalytic mechanism is unknown. The 0.8 A crystal structure of the prolyl isomerase domain of parvulin Par14 shows the electron density of hydrogen atoms between the D74, H42, H123, and T118 side chains. This threonine residue has previously not been associated with catalysis, but a corresponding T152A mutant of Pin1 shows a dramatic reduction of catalytic activity without compromising protein stability. The observed catalytic tetrad is strikingly conserved in Pin1- and parvulin-type proteins and hence constitutes a common feature of small peptidyl prolyl isomerases. PMID- 22081961 TI - Return to military weight standards after pregnancy in active duty working women: comparison of marine corps vs. navy. AB - OBJECTIVE: To compare the likelihood of being within weight standards before and after pregnancy between United States Marine Corps (USMC) and Navy (USN) active duty women (ADW). METHODS: ADW with singleton gestations who delivered at a USMC base were followed for 6 months to determine likelihood of returning to military weight standards. Odds ratio (OR), adjusted odds ratio (AOR) and 95% confidence intervals were calculated; p < 0.05 was considered significant. RESULTS: Similar proportions of USN and USMC ADW were within body weight standards one year prior to pregnancy (79%, 97%) and at first prenatal visit (69%, 96%), respectively. However, USMC ADW were significantly more likely to be within body weight standards at 3 months (AOR 4.30,1.28-14.43) and 6 months after delivery (AOR 9.94, 1.53-64.52) than USN ADW. Weight gained during pregnancy did not differ significantly for the two groups (40.4 lbs vs 44.2 lbs, p = 0.163). The likelihood of spontaneous vaginal delivery was significantly higher (OR 2.52, 1.20-5.27) and the mean birth weight was significantly lower (p = 0.0036) among USMC ADW as compared to USN ADW. CONCLUSIONS: Being within weight standards differs significantly for USMC and USN ADW after pregnancy. PMID- 22081962 TI - Farm management factors associated with bulk tank somatic cell count in Irish dairy herds. AB - The relationship between bulk tank somatic cell count (SCC) and farm management and infrastructure was examined using data from 398 randomly selected, yet representative, Irish dairy farms where the basal diet is grazed grass. Median bulk tank SCC for the farms was 282,887 cells/ml ranging from 82,209 to 773,028 cells/ml. Two questionnaires were administered through face-to-face contact with each farmer. Herd-level factors associated with bulk tank SCC were determined using linear models with annual somatic cell score (i.e., arithmetic mean of the natural logarithm of bulk tank SCC) included as the dependent variable. All herd level factors were analysed individually in separate regression models, which included an adjustment for geographical location of the farm; a multiple regression model was subsequently developed. Management practices associated with low SCC included the use of dry cow therapy, participation in a milk recording scheme and the use of teat disinfection post-milking. There was an association between low SCC and an increased level of hygiene and frequency of cleaning of the holding yard, passageways and cubicles. Herd management factors associated with bulk tank SCC in Irish grazing herds are generally in agreement with most previous studies from confinement systems of milk production. PMID- 22081963 TI - Chronic obstructive pulmonary disease (COPD) rehabilitation at primary health care centres - the KOALA project. AB - BACKGROUND: Implementation of pulmonary rehabilitation in primary health care in Denmark is a new challenge in the management of patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To assess the feasibility of introducing a nationwide web-based tool for data recording and quality assurance in the rehabilitation programmes and to evaluate whether patients are referred correctly according to Danish guidelines for community based COPD rehabilitation. METHODS: Participation in the KOALA project has been offered to the municipalities since October 2007. As of October 2010, 62 health-care centres have been invited to participate. We present summary statistics and correlation analyses of the 1699 patients who have been enrolled so far. RESULTS: Thirty-three municipalities are currently engaged in the KOALA project. Descriptive analyses reveal that 33% of the patients do not meet the criteria for pulmonary rehabilitation in terms of dyspnoea upon exertion at the baseline visit. Furthermore, information on severity of COPD is missing for 18% of the attendants. The majority of the referred patients have moderate COPD, which is in accordance with the intentions of rehabilitation in the community. Statistical analyses show that COPD-level and grade of dyspnoea are positively correlated and expose significant correlations between both COPD-level and dyspnoea and 6 minutes walking distance (6MWD), incremental shuttle walk distance (ISWT) and quality of life. CONCLUSIONS: We conclude that the municipalities in general are interested in the KOALA project as a mean of data recording and sharing and as a quality instrument. Summary statistics show that there is room for improvement in referral and baseline assessments of patients suitable for pulmonary rehabilitation in a community setting. PMID- 22081964 TI - The p66Shc knocked out mice are short lived under natural condition. AB - Deletion of the p66(Shc) gene results in lean and healthy mice, retards aging, and protects from aging-associated diseases, raising the question of why p66(Shc) has been selected, and what is its physiological role. We have investigated survival and reproduction of p66(Shc)-/- mice in a population living in a large outdoor enclosure for a year, subjected to food competition and exposed to winter temperatures. Under these conditions, deletion of p66(Shc) was strongly counterselected. Laboratory studies revealed that p66(Shc)-/- mice have defects in fat accumulation, thermoregulation, and reproduction, suggesting that p66(Shc) has been evolutionarily selected because of its role in energy metabolism. These findings imply that the health impact of targeting aging genes might depend on the specific energetic niche and caution should be exercised against premature conclusions regarding gene functions that have only been observed in protected laboratory conditions. PMID- 22081965 TI - Chemical nature of superhydrophobic aluminum alloy surfaces produced via a one step process using fluoroalkyl-silane in a base medium. AB - Various surface characterization techniques were used to study the modified surface chemistry of superhydrophobic aluminum alloy surfaces prepared by immersing the substrates in an aqueous solution containing sodium hydroxide and fluoroalkyl-silane (FAS-17) molecules. The creation of a rough micronanostructure on the treated surfaces was revealed by scanning electron microscopy (SEM). X-ray photoelectron spectroscopy (XPS) and infrared reflection absorption spectroscopy (IRRAS) confirmed the presence of low surface energy functional groups of fluorinated carbon on the superhydrophobic surfaces. IRRAS also revealed the presence of a large number of OH groups on the hydrophilic surfaces. A possible bonding mechanism of the FAS-17 molecules with the aluminum alloy surfaces has been suggested based on the IRRAS and XPS studies. The resulting surfaces demonstrated water contact angles as high as ~166 degrees and contact angle hystereses as low as ~4.5 degrees . A correlation between the contact angle, rms roughnesses, and the chemical nature of the surface has been elucidated. PMID- 22081966 TI - Functional characterization and target discovery of glycoside hydrolases from the digestome of the lower termite Coptotermes gestroi. AB - BACKGROUND: Lignocellulosic materials have been moved towards the forefront of the biofuel industry as a sustainable resource. However, saccharification and the production of bioproducts derived from plant cell wall biomass are complex and lengthy processes. The understanding of termite gut biology and feeding strategies may improve the current state of biomass conversion technology and bioproduct production. RESULTS: The study herein shows comprehensive functional characterization of crude body extracts from Coptotermes gestroi along with global proteomic analysis of the termite's digestome, targeting the identification of glycoside hydrolases and accessory proteins responsible for plant biomass conversion. The crude protein extract from C. gestroi was enzymatically efficient over a broad pH range on a series of natural polysaccharides, formed by glucose-, xylose-, mannan- and/or arabinose-containing polymers, linked by various types of glycosidic bonds, as well as ramification types. Our proteomic approach successfully identified a large number of relevant polypeptides in the C. gestroi digestome. A total of 55 different proteins were identified and classified into 29 CAZy families. Based on the total number of peptides identified, the majority of components found in the C. gestroi digestome were cellulose-degrading enzymes. Xylanolytic enzymes, mannan- hydrolytic enzymes, pectinases and starch-degrading and debranching enzymes were also identified. Our strategy enabled validation of liquid chromatography with tandem mass spectrometry recognized proteins, by enzymatic functional assays and by following the degradation products of specific 8-amino-1,3,6-pyrenetrisulfonic acid labeled oligosaccharides through capillary zone electrophoresis. CONCLUSIONS: Here we describe the first global study on the enzymatic repertoire involved in plant polysaccharide degradation by the lower termite C. gestroi. The biochemical characterization of whole body termite extracts evidenced their ability to cleave all types of glycosidic bonds present in plant polysaccharides. The comprehensive proteomic analysis, revealed a complete collection of hydrolytic enzymes including cellulases (GH1, GH3, GH5, GH7, GH9 and CBM 6), hemicellulases (GH2, GH10, GH11, GH16, GH43 and CBM 27) and pectinases (GH28 and GH29). PMID- 22081967 TI - Risk of mortality for ventricular arrhythmia in ambulatory LVAD patients. AB - BACKGROUND: There are limited data regarding the incidence and prognostic significance of ventricular arrhythmias (VA) in ambulatory continuous flow left ventricular assist device (LVAD) patients. METHODS: Sixty-one consecutive patients from November 1, 2006 through December 31, 2010 with an LVAD and implantable cardioverter defibrillator that survived to discharge from the LVAD implantation admission were studied. Follow-up began from date of discharge with both devices in situ and ended with death, transplant, on June 1, 2011. Pre-LVAD VA history was related to the primary endpoints of post-LVAD VA, mortality, and the combined endpoint of post-LVAD VA/mortality. RESULTS: During a mean follow-up of 622 days 19 patients (31%) experienced VA (14 episodes of VT, 5 episodes of VF). Pre-LVAD VA was predictive of post-LVAD VA (hazard ratio [HR] 2.91, P = 0.026) and the combined post-LVAD VA/mortality endpoint (HR 2.70, P = 0.021) but only displayed a nonsignificant association with mortality (HR 2.30, P = 0.11). In multivariate analysis, pre-LVAD VA remained a significant predictor of post LVAD VA (HR 2.84, P = 0.03) and the combined post-LVAD VA/mortality endpoint (HR 2.65, P = 0.025). Post-LVAD VA was the strongest univariate predictor of mortality (HR 13.92, P < 0.001) and remained so after multivariate adjustment (HR 9.69, P = 0.001). Post-LVAD VA occurred at a mean of 1 year from mortality events with 45% within 1 month. CONCLUSIONS: Pre-LVAD VA is a significant predictor of post-LVAD VA but not of mortality. VA in the continuous flow LVAD population carries a significant risk of mortality often within the first month. PMID- 22081968 TI - Pediatric liver transplantation - ethical dilemmas in a disabled patient. AB - Allocation of medical resources, especially resources with absolute scarcity such as organs for transplant, is a difficult task. Medical, surgical, and ethical considerations should be evaluated. In solid organ transplantation, ethics committees are the gate keepers that deal with moral philosophy when moral values are in conflict. Often, no good solution to a dilemma in these medical ethics exists. Our case presents split living liver donation for retransplantation in a mentally disabled girl, with few medical ethics principles at stake. PMID- 22081969 TI - Molecular analysis of the crenarchaeal flagellum. AB - The ability to move towards favourable conditions provides fundamental advantages to organisms. Interestingly, flagella as motility structures evolved independently in the bacterial and the archaeal kingdom. Whereas bacterial flagella have been intensively studied, our knowledge regarding the archaeal counterpart is mostly restricted to Euryarchaeota rather than crenarchaeal flagella. We therefore investigated the flagellar assembly system of the crenarchaeal model organism Sulfolobus acidocaldarius in vivo. Promoter studies and qRT-PCR analyses of the flagella gene cluster provided evidence that the expression of the fla genes was induced by tryptone starvation. Moreover, we confirmed presence of a secondary fla promoter within the flaB gene that regulates the transcription of downstream genes flaX-J. Markerless in-frame deletions for all fla genes encoded in the fla gene cluster were constructed. Western blot analysis of all fla deletion strains suggested hierarchical protein interactions during the archaeal flagella assembly. Moreover, functional analysis by thermomicroscopy revealed non-motile cells for each of the mutant strains. Electron micrographs demonstrated that lack of motility coincided with the loss of flagellar assembly. Thus we demonstrated that all seven fla genes are essential for crenarchaeal flagellum assembly and function. PMID- 22081970 TI - Identification of two independent nucleosome-binding domains in the transcriptional co-activator SPBP. AB - Transcriptional regulation requires co-ordinated action of transcription factors, co-activator complexes and general transcription factors to access specific loci in the dense chromatin structure. In the present study we demonstrate that the transcriptional co-regulator SPBP [stromelysin-1 PDGF (platelet-derived growth factor)-responsive element binding protein] contains two independent chromatin binding domains, the SPBP-(1551-1666) region and the C-terminal extended PHD [ePHD/ADD (extended plant homeodomain/ATRX-DNMT3-DNMT3L)] domain. The region 1551 1666 is a novel core nucleosome-interaction domain located adjacent to the AT hook motif in the DNA-binding domain. This novel nucleosome-binding region is critically important for proper localization of SPBP in the cell nucleus. The ePHD/ADD domain associates with nucleosomes in a histone tail-dependent manner, and has significant impact on the dynamic interaction between SPBP and chromatin. Furthermore, SPBP and its homologue RAI1 (retinoic-acid-inducible protein 1), are strongly enriched on chromatin in interphase HeLa cells, and both proteins display low nuclear mobility. RAI1 contains a region with homology to the novel nucleosome-binding region SPBP-(1551-1666) and an ePHD/ADD domain with ability to bind nucleosomes. These results indicate that the transcriptional co-regulator SPBP and its homologue RAI1 implicated in Smith-Magenis syndrome and Potocki Lupski syndrome both belong to the expanding family of chromatin-binding proteins containing several domains involved in specific chromatin interactions. PMID- 22081971 TI - Nurses' perceptions and attitudes towards computerisation in a private hospital. AB - AIMS: To explore nurses' attitudes and level of satisfaction in using the Hospital Information System in clinical practice. BACKGROUND: Application of the Hospital Information System is increasing and there is substantial evidence suggesting that the successful implementation of Hospital Information System is significantly related to nurses' attitudes. However, little information is currently available on the factors influencing those attitudes and their level of satisfaction in Hospital Information System use. DESIGN: Cross-sectional survey. METHODS: A stratified, random sampling of 342 nurses working in a Hong Kong private hospital and using Hospital Information System was recruited. A questionnaire was used to collect data on perceptions, level of satisfaction and attitudes towards Hospital Information System usage. Correlations and linear regressions were used to analyse the data. RESULTS: Multiple linear regression analysis showed that work units, perceived usefulness and information technology support are the three predictors of nurses' attitudes and level of satisfaction with the system. In addition, nurses who have higher perceived ease of use and better satisfaction towards using the system are associated with positive attitude. CONCLUSION: The study results serve to guide the nurse managers to develop information systems based on the nurses' needs. Previous studies regarded nurses' level of satisfaction as a part of nurses' attitude. What is of interest in this study is that nurses' satisfaction level can be viewed as an individual factor affecting nurses' attitudes. With a user-friendly system, nurses tend to be more satisfied and therefore potentially more engaged in its use. This may indirectly improve patient care by saving time on documentation and enhancing communication among departments. RELEVANCE TO CLINICAL PRACTICE: The nurse managers should promote an institutional culture to motivate staff towards positive acceptance of innovation. An effective collaboration with the information technology team would enhance a more efficient exchange of information to understand the complex factors of IT implementation. PMID- 22081973 TI - Membrane activity of tetra-p-guanidinoethylcalix[4]arene as a possible reason for its antibacterial properties. AB - Tetra-p-guanidinoethylcalix[4]arene trifluoroacetate salt (CX1) was synthesized recently as an antibacterial agent. It showed to be active in vitro against various Gram-positive and Gram-negative bacteria. To get more insight in the mechanism of the biological activity of this derivative, it was studied upon interactions with model lipid membranes. Langmuir monolayers were formed with zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine or 1,2-dimyristoyl-sn glycero-3-phosphoethanolamine, and with anionic 1,2-dimyristoyl-sn-glycero-3 phospho-rac-(1-glycerol) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine. The two classes of lipids were used, respectively, as model lipids of the eukaryotic and bacterial cell membranes. The monolayers were exposed to CX1 at different concentrations around the minimum inhibitory concentration found for E. coli . The surface pressure-area and surface potential-area compression isotherms, as well as Brewster angle microscopy and polarization-modulation infrared reflection absorption spectroscopy, were employed to study the monolayers. The results obtained show a higher affinity of CX1 for the anionic lipids, indicating importance of charge-charge interactions. On the basis of a comparative study of the behavior of CX1 and that of p-guanidinoethylphenol trifluoroacetate salt, we propose that interplay of charge-charge and apolar interactions between CX1 and lipids is responsible for the important reorganization of model membranes. This proposal may be helpful in developing new antibacterial calixarene derivatives. PMID- 22081974 TI - Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. AB - BACKGROUND: The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer. METHODS: Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible. RESULTS: Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 +/- 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 +/- 22.9% positively stained cancer cells. CONCLUSIONS: Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further. PMID- 22081975 TI - HIV serostatus disclosure and lived experiences of adolescents at the Transition Clinic of the Infectious Diseases Clinic in Kampala, Uganda: a qualitative study. AB - Most studies on HIV serostatus disclosure and adolescents focus on whether, how and when to disclose to adolescents their HIV diagnosis. Fewer studies have examined HIV serostatus disclosure by adolescents who know they are infected with HIV. This study presents qualitative data examining HIV serostatus and treatment disclosure practices and concerns of young people living with HIV in Uganda and the extent to which they are satisfied with current norms around HIV serostatus and treatment disclosure. We conducted two focus groups and interviewed 20 HIV infected young people aged 15-23 receiving HIV care and treatment at the Transition Clinic in Kampala. Respondents perceived disclosure as a relationship encompassing both communication and self-conduct. Adolescents employed unique strategies to disclose their HIV status, notably joking to "test the waters" and emotionally prepare the other person before later disclosing in a more serious manner. Findings reinforce the idea that HIV disclosure is a process, not a one time event. Interviewees anticipated both positive and negative outcomes of disclosure, including financial and emotional support, stigma, discrimination and rejection. They described a sense of violation of their autonomy when confidentiality was breached by third party disclosure, and also expressed fear of emotional distress for their loved ones. Although adolescents yearned to be in control of information about their HIV status and treatment, they have little space to call their own, and privacy is often compromised, especially because in traditional African settings, young people are considered to be dependents under the full responsibility of caregivers. Further exploration of disclosure outcomes and strategies specific to adolescents can help better tailor interventions towards youth. Antiretroviral therapy programmes should consider counselling for caretakers to appreciate and respect the privacy and disclosure concerns of their HIV-infected children. PMID- 22081977 TI - How is active transport associated with children's and adolescents' physical activity over time? AB - BACKGROUND: As few longitudinal studies have examined how active transport is associated with physical activity among children and adolescents over time, and how active transport tracks through childhood and adolescence, it is important to understand whether physically active children retain their activity patterns through adolescence. This study aimed to examine (a) tracking of active transport and of moderate-to-vigorous physical activity (MVPA) across childhood and adolescence in two age cohorts; and (b) associations between active transport and MVPA at three distinct time-points, over five years. METHODS: This longitudinal study of two cohorts aged 5-6 years (n = 134) and 10-12 years (n = 201) at baseline (T1), in Melbourne, Australia, gathered follow-up data at three (T2) and five years (T3). Walking/cycling to local destinations was survey-reported; while MVPA was recorded using accelerometers and mean time spent daily in MVPA on week days and on weekends was computed. Tracking of these behaviours was examined over five years using General Estimating Equations. Linear regression analyses were performed to examine associations between active transport and MVPA at each time point. RESULTS: Active transport tracked moderately among children (boys, betas = 0.36; girls, betas = 0.51) but not among adolescents. Physical activity tracked moderately (betas value range: 0.33-0.55) for both cohorts. Active transport was not associated with children's MVPA at any time-point, but was associated with adolescent boys' MVPA on week days at T1 (B = 1.37 (95% CI: 0.15, 2.59)), at T2 (B = 1.27 (95% CI: 0.03, 2.51)) and at T3 (B = 0.74 (95% CI: 0.01, 1.47)), and with adolescent girls' MVPA on week days (B = 0.40 (95% CI: 0.04, 0.76)) and on weekends (B = 0.54 (95% CI: 0.16, 0.93)) at T3 only. CONCLUSION: Active transport was associated only with boys' MVPA during early adolescence and with boys' and girls' MVPA during late adolescence. While active transport should be encouraged among all school-aged children, it may provide an important source of habitual physical activity for adolescent girls, in particular, among whom low and declining physical activity levels have been reported world-wide. PMID- 22081976 TI - Antimicrobial properties of amyloid peptides. AB - More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-beta structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape beta-strand-turn beta-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids not only are toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function. PMID- 22081978 TI - Predictors of work-related musculoskeletal disorders among dental hygienists. AB - OBJECTIVES: Work-related musculoskeletal disorders (MSD) have been recognized as a considerable problem for the dental hygiene profession, with the majority of professionals reporting musculoskeletal pain. The aim of this study was to investigate which risk factors may help predict MSD among Australian dental hygienists. METHODS: A modified version of the Standardised Nordic questionnaire was distributed to registered hygienists throughout Australia. RESULTS: Logistic regression analysis revealed a variety of work-related and psychosocial factors that correlate with reported MSD, including scaling tasks, type of practice and work interference in home life. Statistical predictors for non-reporting of MSD included wearing loupes, ergonomics education and wage satisfaction. Concerning is the impact on the profession, with an association between MSD and hygienists considering reducing working hours or even alternate careers. CONCLUSIONS: In general, it appears as though the causes of MSD among dental hygienists may be multifactorial, as may be the solutions to this problem. Further research is required to objectively examine whether controllable variables can be implemented as preventive strategies or interventions for MSD. PMID- 22081980 TI - 2011 Nobel Prize in Physiology or Medicine to three immunologists. PMID- 22081979 TI - Importance of the C2, N7, and C8 positions to the mutagenic potential of 8-Oxo-2' deoxyguanosine with two A family polymerases. AB - 8-Oxo-2'-deoxyguanosine (OdG) is a prominent DNA lesion produced from the reaction of 2'-deoxyguanosine (dG) with reactive oxygen species. While dG directs the insertion of only dCTP during replication, OdG can direct the insertion of either dCTP or dATP, allowing for the production of dG -> dT transversions. When replicated by Klenow fragment-exo (KF-exo), OdG preferentially directs the incorporation of dCTP over dATP, thus decreasing its mutagenic potential. However, when replicated by a highly related polymerase, the large fragment of polymerase I from Bacillus stearothermophilus (BF), dATP incorporation is preferred, and a higher mutagenic potential results. To gain insight into the reasons for this opposite preference and the effects of the C2, N7, and C8 positions on OdG mutagenicity, single-nucleotide insertions of dCTP and/or dATP opposite dG, OdG, and seven of their analogues were examined by steady state kinetics with both KF-exo and BF. Results from these studies suggest that the two enzymes behave similarly and are both sensitive not only to steric and electronic changes within the imidazole ring during both dCTP and dATP incorporation but also to the presence of the C2-exocyclic amine during dATP incorporation. The difference in incorporation preference opposite OdG appears to be due to a somewhat increased sensitivity to structural perturbations during dCTP incorporation with BF. Single-nucleotide extensions past the resulting base pairs were also studied and were not only similar between the two enzymes but also consistent with published ternary crystallographic studies with BF. These results are analyzed in the context of previous biochemical and structural studies, as well as stability studies with the resulting base pairs. PMID- 22081981 TI - A randomized trial investigating an iron-rich bread as a prophylaxis against iron deficiency in pregnancy. AB - The iron-rich bread (2.2 mg iron per 50 g slice) used in the study was developed using Eragrostis tef flour, naturally rich in iron. Iron deficiency is prevalent in pregnancy and compliance with supplements can be low. In this double-blind, randomized trial 34 Caucasian, primiparous antenatal patients were randomized to receive intervention bread or a placebo for 6 weeks. Women consumed on an average of 2.3 slices per day, providing a total of 5.0 mg iron. Using World Health Organisation (2001) haemoglobin cut-offs, 12% of participants eating the iron rich bread were iron deficient by the end of the study compared with 27% in the control group. For other markers of iron status, these were improved in the placebo versus the treatment group. For example, a significant decline in serum iron and transferrin saturation was not observed in this group. Findings demonstrate that other modes of delivery, i.e. food fortification, may be needed to generate 'physiological effects', or further measures are taken to improve intervention compliance. PMID- 22081982 TI - -NH- termination of the Si(111) surface by wet chemistry. AB - For over a quarter of a century the hydrogen-terminated Si(111) single crystalline surface has been the gold standard as a starting point for silicon surface modification chemistry. However, creating a well-defined and stable interface based on Si-N bonds has remained elusive. Despite the fact that azides, nitro compounds, and amines do lead to the formation of surface Si-N, each of these modification schemes produces additional carbon- or oxygen-containing functional groups that in turn react with the surface itself, leaving contaminants that affect the interface properties for any further modification protocols. We describe the preparation of a Si(111) surface functionalized predominantly with Si-NH-Si species based on chlorination followed by the room temperature ammonia treatment utilizing NH(3)-saturated tetrahydrofuran (THF). The obtained surface has been characterized by infrared spectroscopy and X-ray photoelectron spectroscopy. This analysis was supplemented with DFT calculations. This newly characterized surface will join the previously established H-Si(111) and Cl-Si(111) surfaces as a general starting point for the preparation of oxygen and carbon-free interfaces, with numerous potential applications. PMID- 22081983 TI - Gender differences in utilization of preventive care services in the United States. AB - BACKGROUND: The utilization of preventive care services in the United States remains low, despite health-care costs being as high as $2.3 trillion. While gender disparities have been known to exist for utilization of overall health care services, the same issue has not been probed for preventive care utilization. METHODS: A retrospective, cross-sectional study using the 2008 Medical Expenditure Panel Survey (MEPS). Preventive care services common to both genders were included (blood pressure checkup, cholesterol checkup, sigmoidoscopy/colonoscopy, flu shot, and dental checkup). Guideline adherence was determined using clinically accepted guidelines such as Joint National Committee 7 and the American Cancer Society. Descriptive statistics were used to describe the population, and chi-square analysis was used to determine the within group differences between the two genders. A multivariate logistic regression was built to determine the likelihood of guideline adherence based on gender while adjusting for known demographic confounders such as age, race, and ethnicity. RESULTS: There were 33,066 MEPS respondents for 2008. Of these, 4,291 to 30,629 met the inclusion criteria depending on the specific preventive care service being analyzed. Men were found to have significantly lower odds of using blood pressure check (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.32-0.38), cholesterol check (OR 0.64, CI 0.60-0.69), dental check (OR 0.71, CI 0.68-0.75), and flu shots (OR 0.71, CI 0.67-0.76). While men had lower utilization for sigmoidoscopy/colonoscopy, the difference was nonsignificant. CONCLUSIONS: Preventive care utilization was found to be higher in women than in men. The gender disparity issue needs to be explored in greater detail to understand these differences. PMID- 22081984 TI - Does attentional training improve numerical processing in developmental dyscalculia? AB - OBJECTIVE: Recently, a deficit in attention was found in those with pure developmental dyscalculia (DD). Accordingly, the present study aimed to examine the influence of attentional training on attention abilities, basic numerical abilities, and arithmetic in participants who were diagnosed as having DD. METHOD: Nine university students diagnosed as having DD (IQ and reading abilities in the normal range and no indication of attention-deficit hyperactivity disorder) and nine matched controls participated in attentional training (i.e., video game training). RESULTS: First, training modulated the orienting system; after training, the size of the validity effect (i.e., effect of valid vs. invalid) decreased. This effect was comparable in the two groups. Training modulated abnormalities in the attention systems of those with DD, that is, it reduced their enlarged congruity effect (i.e., faster responding when flanking arrows pointed to the same location as a center arrow). Second, in relation to the enumeration task, training reduced the reaction time of the DD group in the subitizing range but did not change their smaller-than-normal subitizing range. Finally, training improved performance in addition problems in both the DD and control groups. CONCLUSIONS: These results imply that attentional training does improve most of the attentional deficits of those with DD. In contrast, training did not improve the abnormalities of the DD group in arithmetic or basic numerical processing. Thus, in contrast to the domain-general hypothesis, the deficits in attention among those with DD and the deficits in numerical processing appear to originate from different sources. PMID- 22081985 TI - A study of asthma severity in adult twins. AB - INTRODUCTION: The tendency to develop asthma runs in families, but whether the severity of asthma symptoms is inherited is not known. OBJECTIVES: The aim of this study was to examine whether genetic factors influence the variation in the severity of asthma. METHODS: Of a sample of 21 133 adult twins from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins) who themselves and/or their co-twins reported a history of asthma at a questionnaire survey were clinically examined. The severity of asthma symptoms was graded according to a clinical interview, and markers of airway impairment and allergy were measured. RESULTS: After adjusting for confounders, genetic factors explained 24% (10%-37%), P = 0.0004, of the variation in overall asthma symptom severity, whereas non-shared environment accounted for the remaining 76% of the variation. A significant genetic component was also found for the severity of specific asthma symptoms; wheezing 12% (3%-22%), P = 0.007 and shortness of breath 17% (7%-27%), P = 0.0006, but not for chest tightness and cough. Asthma symptom severity correlated weakly with rhinitis severity as well as with objective markers of lung function, airway inflammation, airway responsiveness and allergic sensitization. CONCLUSION: The individual variation in asthma symptom severity is to some degree influenced by genetic factors, but environmental factors explain the main part of the variation. The genetic architectures underlying the severity of asthma symptoms and objectively measured asthma-related traits, respectively, seem to differ. PMID- 22081986 TI - Global trends in milk quality: implications for the Irish dairy industry. AB - The quality of Irish agricultural product will become increasingly important with the ongoing liberalisation of international trade. This paper presents a review of the global and Irish dairy industries; considers the impact of milk quality on farm profitability, food processing and human health, examines global trends in quality; and explores several models that are successfully being used to tackle milk quality concerns. There is a growing global demand for dairy products, fuelled in part by growing consumer wealth in developing countries. Global dairy trade represents only 6.2% of global production and demand currently outstrips supply. Although the Irish dairy industry is small by global standards, approximately 85% of annual production is exported annually. It is also the world's largest producer of powdered infant formula. Milk quality has an impact on human health, milk processing and on-farm profitability. Somatic cell count (SCC) is a key measure of milk quality, with a SCC not exceeding 400,000 cells/ml (the EU milk quality standard) generally accepted as the international export standard. There have been ongoing improvements in milk quality among both established and emerging international suppliers. A number of countries have developed successful industry-led models to tackle milk quality concerns. Based on international experiences, it is likely that problems with effective translation of knowledge to practice, rather than incomplete knowledge per se, are the more important constraints to national progress towards improved milk quality. PMID- 22081987 TI - High throughput screening of hydrolytic enzymes from termites using a natural substrate derived from sugarcane bagasse. AB - BACKGROUND: The description of new hydrolytic enzymes is an important step in the development of techniques which use lignocellulosic materials as a starting point for fuel production. Sugarcane bagasse, which is subjected to pre-treatment, hydrolysis and fermentation for the production of ethanol in several test refineries, is the most promising source of raw material for the production of second generation renewable fuels in Brazil. One problem when screening hydrolytic activities is that the activity against commercial substrates, such as carboxymethylcellulose, does not always correspond to the activity against the natural lignocellulosic material. Besides that, the macroscopic characteristics of the raw material, such as insolubility and heterogeneity, hinder its use for high throughput screenings. RESULTS: In this paper, we present the preparation of a colloidal suspension of particles obtained from sugarcane bagasse, with minimal chemical change in the lignocellulosic material, and demonstrate its use for high throughput assays of hydrolases using Brazilian termites as the screened organisms. CONCLUSIONS: Important differences between the use of the natural substrate and commercial cellulase substrates, such as carboxymethylcellulose or crystalline cellulose, were observed. This suggests that wood feeding termites, in contrast to litter feeding termites, might not be the best source for enzymes that degrade sugarcane biomass. PMID- 22081988 TI - Retrospective comparison of semipermanent and permanent cementation of implant supported single crowns and FDPs with regard to the incidence of survival and complications. AB - PURPOSE: To retrospectively compare the fixation modalities semipermanent and permanent for all cemented single crowns and Fixed Dental Prostheses (FDPs) placed at the Department of Prosthodontics in the years 2002 to 2010 with regard to the incidence of survival and complications. MATERIALS AND METHODS: Two hundred forty-one patients (48.5% male, mean age 57.3 years) received 166 FDPs and 232 single crowns. A total of 50.6% of the FDPs and 54.7% of the single crowns were fixed using semipermanent cements. Aside from fixation, age, gender, type, location, and material of the suprastructures were assessed as possible factors affecting complications, namely de-cementation, chipping, framework, or abutment fracture. RESULTS: During an observation period of up to 6.6 years (mean 2.24 years; standard deviation 1.38), the survival rates were 96.4% and 100% for FDPs (semipermanent/permanent cementation), and 98.4% and 92.4% for single crowns (semipermanent/permanent). The success rates achieved, counting every complication, for the FDPs were 61.9% and 70.7% (semipermanent/permanent) and for single crowns were 75.6% and 77.1% (semipermanent/permanent). The cement used had a significant effect on loss of retention of the FDPs (p = .006), but no significant effect on the retention of the single crowns. Cementation procedure exhibited no significant impact on chipping for both FDPs and single crowns. The frequency of framework or abutment fractures was too low for further statistical analyses. CONCLUSION: Both semipermanent and permanent cementation of FDPs and single crowns resulted in high survival rates. Within the limitations of the study design, because of the amount of chairside aftercare required, implant borne FDPs could be recommended for permanent cementation. PMID- 22081989 TI - Stimulus-induced dissociation of neuronal firing rates and local field potential gamma power and its relationship to the resonance blood oxygen level-dependent signal in macaque primary visual cortex. AB - The functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signal is regularly used to assign neuronal activity to cognitive function. Recent analyses have shown that the local field potential (LFP) gamma power is a better predictor of the fMRI BOLD signal than spiking activity. However, LFP gamma power and spiking activity are usually correlated, clouding the analysis of the neural basis of the BOLD signal. We show that changes in LFP gamma power and spiking activity in the primary visual cortex (V1) of the awake primate can be dissociated by using grating and plaid pattern stimuli, which differentially engage surround suppression and cross-orientation inhibition/facilitation within and between cortical columns. Grating presentation yielded substantial V1 LFP gamma frequency oscillations and significant multi unit activity. Plaid pattern presentation significantly reduced the LFP gamma power while increasing population multi-unit activity. The fMRI BOLD activity followed the LFP gamma power changes, not the multi-unit activity. Inference of neuronal activity from the fMRI BOLD signal thus requires detailed a priori knowledge of how different stimuli or tasks activate the cortical network. PMID- 22081990 TI - Allergic reaction to suture material after an ICD procedure: device infection mimicry. AB - When an implanted device is infected, complete explantation of the device system, including lead extraction, is usually required. Superficial problems with wound healing may be managed more conservatively, but distinguishing between a surface process and deeper infection can pose a clinical challenge. We present a case of poor wound healing after an ICD pocket revision procedure, and an allergic reaction to the suture material was found to be the cause. Diagnosis, management, and future implications of suture allergy are discussed. PMID- 22081991 TI - Transjugular liver biopsy in pediatric patients with left split liver transplantation and severe coagulation impairment. AB - The aim of this study is to report our experience in TJLB performed in pediatric patients who underwent partial LT using a left lateral segments graft. Eight consecutive TJLBs were performed in six patients with contraindication to percutaneous biopsy owing to severe coagulation impairment and ascites. All procedures were performed using an 18-gauge automated core needle biopsy. Median age of the patients was 44 months (range, 11-198). Median patients' weight was 13 kg (range, 8-45). Technical success was achieved in all cases without complications. The specimens were adequate for the diagnosis in all cases. PMID- 22081992 TI - An exploration of Singaporean parental experiences in managing school-aged children's postoperative pain: a descriptive qualitative approach. AB - AIMS AND OBJECTIVES: To enhance understanding of the experience of parents in managing their children's postoperative pain in Singapore. BACKGROUND: Parents play a significant role in their hospitalised child's postoperative pain care. Their active involvement may contribute to accurate pain assessment and effective pain management for their child. However, there is a lack of in-depth research exploring the experience of parents involved in their children's postoperative pain management. DESIGN: This study adopted a descriptive qualitative approach, which is situated in the interpretive paradigm. METHOD: Semi-structured interviews were conducted to collect data from 14 parents whose children were hospitalised in one of the three paediatric surgical wards in a hospital in Singapore in December 2009. Thematic analysis was used to analyse the data. RESULTS: Three themes were identified: 'Actions used by parents to alleviate their child's postoperative pain', 'Factors influencing parents' management of their child's postoperative pain' and 'Parents' needs in the process of caring for their child's postoperative pain'. Parents used a range of non pharmacological pain relief interventions for their child. Parental roles and expectations, bond between parent and child, support from nurses, family and own religious beliefs, as well as children's age and maturity level were factors which promoted parental participation, whereas parents' negative feelings, knowledge deficit and nurses' busy schedule were hindering factors. Parents expressed needs for more involvement in their child's care, adequate rest and information support from nurses. CONCLUSIONS: This study highlights the importance of involving parents in their child's postoperative pain management. It provides evidence for health care professionals to pay attention to factors that may influence parental participation and, therefore, guide their practice. RELEVANCE TO CLINICAL PRACTICE: Nurses need to provide parents with support and education to facilitate their roles and improve their child's postoperative pain management. PMID- 22081993 TI - Computationally-guided optimization of a docking hit to yield catechol diethers as potent anti-HIV agents. AB - A 5-MUM docking hit has been optimized to an extraordinarily potent (55 pM) non nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (FEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity. PMID- 22081994 TI - The Western Norway mental health interface study: a controlled intervention trial on referral letters between primary care and specialist mental health care. AB - BACKGROUND: Referral letters are the main communication means between Primary and Specialised Mental Health Care. However, studies of referral letters reveal that they lack important information, and how this lack of information affects the care for patients is unknown. This study aims to explore if and to what degree the quality of referral letters within Mental Health Care for adults can be improved and the potential improvement's impact on defined patient, professional and organisational related outcomes. METHODS AND DESIGN: A controlled study with pre and post test will be prepared and accomplished to explore the correlation between the content of referral letters and outcomes of the care for the referred patients. The study is performed in accordance with the guideline of the Medical Research Council on development and evaluation of complex interventions. Using a mixed method design, a stepwise model will be conducted: Firstly, process and outcome measures will be developed and tested. Secondly, by these measures, the results from an intervention group of General Practitioners (GPs) who receive a complex quality improvement intervention will be compared with results from a control group who perform "care as usual". Compliance to the introduced guideline will be measured as a mediator. DISCUSSION: The Western Norway Mental Health Interface Study is among the first trials to evaluate the impact of the quality of referral letters on the organization of care. This study will provide information that will be usable for healthcare managers and clinicians in both Primary and Specialised Care settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01374035. PMID- 22081995 TI - Reliability, reproducibility, and validation of five major histological scoring systems for experimental articular cartilage repair in the rabbit model. AB - Histological evaluation of the repair tissue is a main pillar in the advancing field of experimental articular cartilage repair. Despite their widespread use, the major histological scoring systems for cartilage repair have seldom been validated. We tested the hypotheses (1) that elementary scores have a better reproducibility compared with more complex systems and (2) that the data from these different histological scores correlate with the DNA and proteoglycan contents of the repair tissue. A total of 1,165 observations of cartilage repair based on histological sections (n=233) from an experimental investigation on the repair of standardized osteochondral defects in vivo were made by three investigators with different levels of experience in cartilage research to determine the inter- and intra-observer reproducibility of elementary (Pineda and Wakitani score) and complex (O'Driscoll, Sellers, Fortier score) histological grading systems. DNA and proteoglycan contents of the repair tissues from simultaneously created defects were determined and correlated with histological (a) overall score values, (b) matrix staining, and (c) cellular characteristics of the five scores. Finally, applying the proteoglycan content as validating test, sensitivity, and specificity of the grading systems were assessed. All histological scores provided high intra- (Pearson r=0.92-0.99) and inter-observer reliability (intra-class correlation=0.94-0.99), low numerical intra- and inter observer differences, and high internal correlations (Spearman's rho=0.63-0.91). No disparity in reliability and reproducibility was detected between elementary and complex scores or between investigators with different levels of experience (all p>0.05). Individual histological overall score values did not correlate with proteoglycan contents but with DNA contents of the repair tissue (O'Driscoll, Wakitani, Sellers score). In all systems, proteoglycan contents did not correlate with matrix staining (all p>0.05), but histological cellular characteristics correlated with total cell numbers (p<0.001). These data indicate that both elementary and comprehensive histological scores are suited to quantify cartilage repair. Histological and biochemical evaluations may serve as complementary tools to assess articular cartilage repair in vivo. PMID- 22081996 TI - A molecular switch based on current-driven rotation of an encapsulated cluster within a fullerene cage. AB - By scanning tunneling microscopy imaging and electronic structure theory, we investigate a single-molecule switch based on tunneling electron-driven rotation of a triangular Sc3N cluster within an icosahedral C80 fullerene cage among three pairs of enantiomorphic configurations. Bias-dependent action spectra and modeling implicate the antisymmetric stretch vibration of Sc3N cluster as the gateway for energy transfer from the tunneling electrons into the cluster rotation. Hierarchical switching of conductivity among multiple stationary states while maintaining a constant molecular shape, offers an advantage for the integration of endohedral fullerene-based single-molecule switches into multiple logic state molecular devices. PMID- 22081997 TI - Cholesterol effect on water permeability through DPPC and PSM lipid bilayers: a molecular dynamics study. AB - Water permeability of two different lipid bilayers of dipalmitoylphosphatidylcholine (DPPC) and palmitoylsphingomyelin (PSM) in the absence and presence of cholesterol (0-50 mol %) have been studied by molecular dynamics simulations to elucidate the molecular mechanism of the reduction in water leakage across the membranes by the addition of cholesterol. An enhanced free energy barrier was observed in these membranes with increased cholesterol concentration, and this was explained by the reduced cavity density around the cholesterol in the hydrophobic membrane core. There was an increase of trans conformers in the hydrophobic lipid chains adjacent to the cholesterol, which reduced the cavity density. The enhanced free energy barrier was found to be the main reason to reduce the water permeability with increased cholesterol concentration. At low cholesterol concentrations the PSM bilayer exhibited a higher free energy barrier than the DPPC bilayer for water permeation, while at greater than 30 mol % of cholesterol the difference became minor. This tendency for the PSM and DPPC bilayers to resemble each other at higher cholesterol concentrations was similar to commonly observed trends in several structural properties, such as order parameters, cross-sectional area per molecule, and cavity density profiles in the hydrophobic regions of bilayer membranes. These results demonstrate that DPPC and PSM bilayers with high cholesterol contents possess similar physical properties, which suggests that the solubility of cholesterol in these lipid bilayers has importance for an understanding of multicomponent lipid membranes with cholesterol. PMID- 22081998 TI - Brain-derived neurotrophic factor expression is repressed during myogenic differentiation by miR-206. AB - Brain-derived neurotrophic factor (BDNF) is required for efficient skeletal muscle regeneration and perturbing its expression causes abnormalities in the proliferation and differentiation of skeletal muscle cells. In this study, we investigated the mechanism of BDNF suppression that occurs during myogenic differentiation. BDNF is expressed at the mRNA level as two isoforms that differ in the length of their 3'UTRs as a result of alternative cleavage and polyadenylation. Sequence analysis revealed the presence of three miR-206 target sites in the long BDNF 3'UTR (BDNF-L), whereas only one site was found in the short mRNA BDNF 3'UTR (BDNF-S). miR-206 is known to regulate the differentiation of C2C12 myoblasts and its expression is induced during the transition from myoblasts to myotubes. We thus examined whether miR-206-mediated suppression is responsible for the expression pattern of BDNF during myogenic differentiation. BDNF-L was suppressed to a greater extent than BDNF-S during differentiation of C2C12 myoblasts. Transfection of a miR-206 precursor decreased activity of reporters representative of the BDNF-L 3'UTR, but not BDNF-S 3'UTR, and repressed endogenous BDNF mRNA levels. This suppression was found to be dependent on the presence of multiple miR-206 target sites in the BDNF-L 3'UTR. Conversely, suppression of miR-206 levels resulted in de-repression of BDNF 3'UTR reporter activity and increased endogenous BDNF-L mRNA levels. A receptor for BDNF, p75(NTR) , was also suppressed during differentiation and in response to miR-206, but this appeared to not be entirely mediated via a miR-206 target site its 3'UTR. Based on these observations, BDNF represents a novel target through which miR-206 controls the initiation and maintenance of the differentiated state of muscle cells. These results further suggest that miR-206 might play a role in regulating retrograde signaling of BDNF at the neuromuscular junction. PMID- 22081999 TI - Optimisation of whole blood and plasma manganese assay by ICP-MS without use of a collision cell. AB - BACKGROUND: Manganese (Mn) toxicity has been reported in patients receiving total parenteral nutrition. To avoid unnecessary exposure it is recommended by NICE (National Institute for Clinical Excellence) that blood Mn concentrations are monitored. The aim of the study was to develop a method using inductively coupled plasma mass spectrometry (ICP-MS) for the reliable determination of Mn in plasma and whole blood, as indices of acute and chronic exposure. METHODS: Whole blood and plasma samples were prepared by appropriate dilution (diluent containing 0.005% Triton X-100, 0.2% propan-2-ol, 0.2% butan-1-ol and 1% nitric acid) addition of an internal standard gallium, followed by centrifugation to remove cell debris. Thermo Fisher Scientific ExCell and X Series ICP-MS instruments were used to define and correct for polyatomic interference on Mn assay. RESULTS: Mn was quantified at mass 55 using aqueous calibration and the polyatomic interference from FeH was successfully eliminated by modified (Xt) skimmer cones but not with the collision cell (collision gas 7% H2 in He, flow rate 4-7 mL/min). The assay was validated showing good precision, limit of detection and percentage recovery. Good agreement was observed with the All Laboratory Trimmed Mean of External Quality Assurance samples y (in house)=1.1 (ALTM)-45.0 between values of 250 and 750 nmol/L. CONCLUSIONS: A method has been developed using ICP MS for the analysis of whole blood and plasma Mn incorporating a novel method of eliminating interference by utilizing the different geometries of the Xt interface cones. The procedure is simple and robust with good precision and recovery over a wide dynamic range. PMID- 22082000 TI - Methylation of miR-34a, miR-34b/c, miR-124-1 and miR-203 in Ph-negative myeloproliferative neoplasms. AB - BACKGROUND: MicroRNA (miR) miR-34a, -34b/c, -124-1 and -203 are tumor suppressor miRs implicated in carcinogenesis. METHODS: We studied DNA methylation of these miRs in Philadelphia-negative (Ph-ve) myeloproliferative neoplasms (MPNs). Methylation-specific PCR (MSP), verified by direct sequencing of the methylated MSP products, was performed in cell lines, normal controls and diagnostic marrow samples of patients with MPNs. RESULTS: Methylation of these miRs was absent in the normal controls. miR-34b/c were homozygously methylated in HEL cells but heterozygously in MEG-01. In HEL cells, homozygous miR-34b/c methylation was associated with miR silencing, and 5-aza-2'-deoxycytidine treatment led to re expression of both miR-34b and miR-34c, consistent with that both miRs are under the regulation of the same promoter CpG island. miR-34a was heterozygously methylated in MEG-01 and K-562. miR-203 was completely unmethylated in K-562 and SET-2 but no MSP amplification was found in both HEL and MEG-01, suggestive of miR deletion. In primary samples, four each had miR-34b/c and -203 methylation, in which two had concomitant methylation of miR-34b/c and -203. miR-34a was methylated in one patient and none had methylation of miR-124-1. Seven patients (15.6%) had methylation of at least one of the four miRs. miR methylation did not correlate with clinical parameters, disease complications or JAK2 V617F mutation. CONCLUSION: This is the first report of miR hypermethylation in MPNs. miR-203 hypermethylation is not specific to Ph+ve leukemias but also present in Ph-ve MPNs. miR-34b/c methylation was associated with reversible miR silencing. There was no correlation of miR methylation with clinical demographic data or outcome. PMID- 22082001 TI - Structure and stability of higher-order human telomeric quadruplexes. AB - G-quadruplex formation in the sequences 5'-(TTAGGG)(n) and 5'(TTAGGG)(n)TT (n = 4, 8, 12) was studied using circular dichroism, sedimentation velocity, differential scanning calorimetry, and molecular dynamics simulations. Sequences containing 8 and 12 repeats formed higher-order structures with two and three contiguous quadruplexes, respectively. Plausible structures for these sequences were determined by molecular dynamics simulations followed by experimental testing of predicted hydrodynamic properties by sedimentation velocity. These structures featured folding of the strand into contiguous quadruplexes with mixed hybrid conformations. Thermodynamic studies showed the strands folded spontaneous to contain the maximum number contiguous quadruplexes. For the sequence 5'(TTAGGG)(12)TT, more than 90% of the strands contained completely folded structures with three quadruplexes. Statistical mechanical-based deconvolution of thermograms for three quadruplex structures showed that each quadruplex melted independently with unique thermodynamic parmameters. Thermodynamic analysis revealed further that quadruplexes in higher-ordered structures were destabilized relative to their monomeric counterparts, with unfavorable coupling free energies. Quadruplex stability thus depends critically on the sequence and structural context. PMID- 22082002 TI - Improved Bevirimat resistance prediction by combination of structural and sequence-based classifiers. AB - BACKGROUND: Maturation inhibitors such as Bevirimat are a new class of antiretroviral drugs that hamper the cleavage of HIV-1 proteins into their functional active forms. They bind to these preproteins and inhibit their cleavage by the HIV-1 protease, resulting in non-functional virus particles. Nevertheless, there exist mutations in this region leading to resistance against Bevirimat. Highly specific and accurate tools to predict resistance to maturation inhibitors can help to identify patients, who might benefit from the usage of these new drugs. RESULTS: We tested several methods to improve Bevirimat resistance prediction in HIV-1. It turned out that combining structural and sequence-based information in classifier ensembles led to accurate and reliable predictions. Moreover, we were able to identify the most crucial regions for Bevirimat resistance computationally, which are in line with experimental results from other studies. CONCLUSIONS: Our analysis demonstrated the use of machine learning techniques to predict HIV-1 resistance against maturation inhibitors such as Bevirimat. New maturation inhibitors are already under development and might enlarge the arsenal of antiretroviral drugs in the future. Thus, accurate prediction tools are very useful to enable a personalized therapy. PMID- 22082003 TI - Corticomotor representation to a human forearm muscle changes following cervical spinal cord injury. AB - Functional imaging studies, using blood oxygen level-dependent signals, have demonstrated cortical reorganization of forearm muscle maps towards the denervated leg area following spinal cord injury (SCI). The extent of cortical reorganization was predicted by spinal atrophy. We therefore expected to see a similar shift in the motor output of corticospinal projections of the forearm towards more denervated lower body parts in volunteers with cervical injury. Therefore, we used magnetic resonance imaging-navigated transcranial magnetic stimulation (TMS) to non-invasively measure changes in cortical map reorganization of a forearm muscle in the primary motor cortex (M1) following human SCI. We recruited volunteers with chronic cervical injuries resulting in bilateral upper and lower motor impairment and severe cervical atrophy and healthy control participants. All participants underwent a T1-weighted anatomical scan prior to the TMS experiment. The motor thresholds of the extensor digitorum communis muscle (EDC) were defined, and its cortical muscle representation was mapped. The centre of gravity (CoG), the cortical silent period (CSP) and active motor thresholds (AMTs) were measured. Regression analysis was used to investigate relationships between trauma-related anatomical changes and TMS parameters. SCI participants had increased AMTs (P = 0.01) and increased CSP duration (P = 0.01). The CoG of the EDC motor-evoked potential map was located more posteriorly towards the anatomical hand representation of M1 in SCI participants than in controls (P = 0.03). Crucially, cord atrophy was negatively associated with AMT and CSP duration (r(2) >= 0.26, P < 0.05). In conclusion, greater spinal cord atrophy predicts changes at the cortical level that lead to reduced excitability and increased inhibition. Therefore, cortical forearm motor representations may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm following SCI. PMID- 22082004 TI - Role of titanium dioxide nanoparticles in the elevated uptake and retention of cadmium and zinc in Daphnia magna. AB - Titanium dioxide nanoparticles (nano-TiO(2)) are now widely applied in consumer products, and the dispersion of nano-TiO(2) may adsorb metals and modify their behavior and bioavailability in the aquatic environment. In the present study, the aqueous uptake, dietary assimilation efficiency (AE), and efflux rate constant (k(e)) of two toxic metals (cadmium-Cd, and zinc-Zn) adsorbed on nano TiO(2) in a freshwater zooplankton Daphnia magna were quantified. The biokinetics was then compared to daphnids that were exposed only to dissolved metals as controls. The aqueous uptake of Cd and Zn involved an initial rapid uptake and then an apparent saturation, and the uptake of metals was accompanied by an ingestion of nano-TiO(2). The AEs of Cd and Zn adsorbed on nano-TiO(2) were 24.6 +/- 2.4-44.5 +/- 3.7% and 30.4 +/- 3.4-51.8 +/- 5.0%, respectively, and decreased with increasing concentrations of nano-TiO(2). Furthermore, the difference between the AEs of Cd and Zn indicated that the desorption of Cd and Zn from nano TiO(2) may have occurred within the gut of daphnids. With the use of algae as carrier, the AEs of Cd and Zn adsorbed on nano-TiO(2) were significantly higher than those of Cd and Zn directly from nano-TiO(2). The efflux rate constants of Cd and Zn adsorbed on nano-TiO(2) in the zooplankton were significantly lower than those of Cd and Zn not adsorbed on nano-TiO(2). Our study shows that the uptake and retention of toxic metals is enhanced when they are adsorbed on nano TiO(2), and suggests more attention be paid to the potential influences of nano TiO(2) on the bioavailability and toxicity of other contaminants. PMID- 22082005 TI - Induction of group IVC phospholipase A2 in allergic asthma: transcriptional regulation by TNFalpha in bronchoepithelial cells. AB - Airway inflammation in allergen-induced asthma is associated with eicosanoid release. These bioactive lipids exhibit anti- and pro-inflammatory activities with relevance to pulmonary pathophysiology. We hypothesized that sensitization/challenge using an extract from the ubiquitous fungus Aspergillus fumigatus in a mouse model of allergic asthma would result in altered phospholipase gene expression, thus modulating the downstream eicosanoid pathway. We observed the most significant induction in the group IVC PLA2 (phospholipase A2) [also known as cPLA2gamma (cytosolic PLA2gamma) or PLA2G4C]. Our results infer that A. fumigatus extract can induce cPLA2gamma levels directly in eosinophils, whereas induction in lung epithelial cells is most likely to be a consequence of TNFalpha (tumour necrosis factor alpha) secretion by A. fumigatus activated macrophages. The mechanism of TNFalpha-dependent induction of cPLA2gamma gene expression was elucidated through a combination of promoter deletions, ChIP (chromatin immunoprecipitation) and overexpression studies in human bronchoepithelial cells, leading to the identification of functionally relevant CRE (cAMP-response element), NF-kappaB (nuclear factor kappaB) and E-box promoter elements. ChIP analysis demonstrated that RNA polymerase II, ATF-2 (activating transcription factor 2)-c-Jun, p65-p65 and USF (upstream stimulating factor) 1-USF2 complexes are recruited to the cPLA2gamma enhancer/promoter in response to TNFalpha, with overexpression and dominant-negative studies implying a strong level of co-operation and interplay between these factors. Overall, our results link cytokine-mediated alterations in cPLA2gamma gene expression with allergic asthma and outline a complex regulatory mechanism. PMID- 22082006 TI - Mini-scar inguinal herniotomy in selected children: comparative analysis of safety, effectiveness, and parents' satisfaction. AB - INTRODUCTION: Inguinal herniotomy in children is still dominated by conventional open inguinal herniotomy (COIH) as laparoscopic techniques have yet to demonstrate clear advantages. A technical modification that minimizes the incision of COIH in selected children can offer another minimally invasive alternative. A comparative analysis of safety, efficacy, and parental attitudes between mini-scar inguinal herniotomy (MSIH) and COIH was performed. MATERIALS AND METHODS: All inguinal herniotomy cases performed between January 2008 and April 2010 were reviewed. Patients who were younger than 6 months, presented with complicated hernias, or had an associated hydrocele were excluded. In the MSIH group the final scar length was prospectively measured and then retrospectively compared with a matched group of COIH. Parents in both groups were then interviewed using a standardized questionnaire to inquire about operative outcomes, their satisfaction level, and perception of the incision size. RESULTS: Of the 145 patients identified, 113 (79%) had completed the parental phone interview at a mean interval of 275+/-212 days. Forty (35%) underwent MSIH with a mean final incision length of 7.7+/-2 mm, and 73 (65%) underwent COIH. The two groups were similar in age, sex, and hernias' sides. Postoperative complication including recurrence rates did not differ between MSIH and COIH (2.5% versus 6.8%, P=.4). However, parents in the MSIH group were more likely to notice that the scar was smaller than what they have expected (odds ratio, 4.9; 95% confidence interval, 2.1-11.9) and were more likely to be very satisfied (odds ratio, 10.8; 95% confidence interval, 3.1-38). CONCLUSION: The safety and efficacy of MSIH are comparable to those of COIH. However, in the MSIH group, parents are more likely to notice the smaller scar, which might improve their satisfaction. PMID- 22082007 TI - Using conventional 3- and 5-mm straight instruments in laparoendoscopic single site pyeloplasty in children. AB - BACKGROUND: Laparoendoscopic single-site surgery (LESS) remains limited to a few relatively simple procedures in the field of pediatric surgery. We performed LESS pyeloplasty in children using conventional straight instruments and ports, and reviewed the perioperative data to evaluate the feasibility of this technique in pediatric patients. METHODS: Twenty-two consecutive patients with unilateral pelvic ureteral junction obstruction underwent LESS pyeloplasty. Their ages ranged from 2 to 134 months (mean: 56.9 months). Two 3-mm and one 5-mm conventional ports were placed in the single incision inside the umbilicus. Conventional 3-mm laparoscopic instruments and a 30-degree 5-mm camera were used for Anderson-Hynes pyeloplasty. A F4.7 or F3 pigtail stent was introduced through one of the instrument ports. A drainage was placed next to the anastomosis, which exited via the umbilical ring incision. The stent was removed 6 weeks postoperatively. RESULTS: All cases were successfully completed with no need for extra-umbilical incisions. The mean operative time was 198 minutes (range: 150 270 minutes). All patients could tolerate oral food intake on postoperative day 1. One case (4.5%) developed symptoms of anastomosis obstruction and required open renal stoma. No other significant complications occurred. CONCLUSION: LESS pyeloplasty is technically feasible in children. However, further experience and longer follow-up are necessary to appropriately evaluate the benefits and limitations of this technique. PMID- 22082009 TI - Assessment of alcohol problems using AUDIT in a prison setting: more than an 'aye or no' question. AB - BACKGROUND: Alcohol problems are a major UK and international public health issue. The prevalence of alcohol problems is markedly higher among prisoners than the general population. However, studies suggest alcohol problems among prisoners are under-detected, under-recorded and under-treated. Identifying offenders with alcohol problems is fundamental to providing high quality healthcare. This paper reports use of the AUDIT screening tool to assess alcohol problems among prisoners. METHODS: Universal screening was undertaken over ten weeks with all entrants to one male Scottish prison using the AUDIT standardised screening tool and supplementary contextual questions. The questionnaire was administered by trained prison officers during routine admission procedures. Overall 259 anonymised completed questionnaires were analysed. RESULTS: AUDIT scores showed a high prevalence of alcohol problems with 73% of prisoner scores indicating an alcohol use disorder (8+), including 36% having scores indicating 'possible dependence' (20-40). AUDIT scores indicating 'possible dependence' were most apparent among 18-24 and 40-64 year-olds (40% and 56% respectively). However, individual questions showed important differences, with younger drinkers less likely to demonstrate habitual and addictive behaviours than the older age group. Disparity between high levels of harmful/hazardous/dependent drinking and low levels of 'treatment' emerged (only 27% of prisoners with scores indicating 'possible dependence' reported being 'in treatment'). Self-reported associations between drinking alcohol and the index crime were identified among two-fifths of respondents, rising to half of those reporting violent crimes. CONCLUSIONS: To our knowledge, this is the first study to identify differing behaviours and needs among prisoners with high AUDIT score ranges, through additional analysis of individual questions. The study has identified high prevalence of alcohol use, varied problem behaviours, and links across drinking, crime and recidivism, supporting the argument for more extensive provision of alcohol-focused interventions in prisons. These should be carefully targeted based on initial screening and assessment, responsive, and include care pathways linking prisoners to community services. Finally, findings confirm the value and feasibility of routine use of the AUDIT screening tool in prison settings, to considerably enhance practice in the detection and understanding of alcohol problems, improving on current more limited questioning (e.g. 'yes or no' questions). PMID- 22082008 TI - Retooling manganese(III) porphyrin-based peroxynitrite decomposition catalysts for selectivity and oral activity: a potential new strategy for treating chronic pain. AB - Redox-active metalloporphyrins represent the most well-characterized class of catalysts capable of attenuating oxidative stress in vivo through the direct interception and decomposition of superoxide and peroxynitrite. While many interesting pharmacological probes have emerged from these studies, few catalysts have been developed with pharmaceutical properties in mind. Herein, we describe our efforts to identify new Mn(III)-porphyrin systems with enhanced membrane solubilizing properties. To this end, seven new Mn(III)-tetracyclohexenylporphyin (TCHP) analogues, 7, 10, 12, 15, and 16a-c, have been prepared in which the beta fused cyclohexenyl rings provide a means to shield the charged metal center from the membrane during passive transport. Compounds 7, 15, and 16a-c have been shown to be orally active and potent analgesics in a model of carrageenan-induced thermal hyperalgesia. In addition, oral administration of compound 7 (10-100 mg/kg, n=5) has been shown to dose dependently reverse mechano-allodynia in the CCI model of chronic neuropathic pain. PMID- 22082010 TI - A comparison between endodontics and implantology: an 8-year retrospective study. AB - PURPOSE: The aim of this study was to compare endodontic and implant treatments and to evaluate their predictability over an 8-year period on the basis of an analysis of survival data and a retrospective clinical study. MATERIALS AND METHODS: A group of 40 partially edentulous patients were selected for this study. Their teeth had been endodontically treated and rehabilitated using gold alloy and ceramic restorations. In these patients, 65 osseointegrated implants were restored with single gold alloy-ceramic crowns and monitored on a yearly basis for 8 years with standardized periapical radiographs, using a polivynilsiloxane occlusal key as a positioner. A total of nine patients who did not attend the yearly follow-up were excluded from the study. The Melloning and Triplett criteria were used to evaluate the clinical results obtained in the implant sites. The clinical results of the 56 endodontically treated teeth, restored with the fixed prosthesis of 40 patients, were analyzed according to probing depth as well as an assessment of the correct apical and coronal seals. The survival rate was calculated using the Kaplan-Meier method and the statistical significance was calculated using the chi-square test. RESULTS: During the follow-up of the endodontically treated elements, seven failures were detected (83.34%) and the success rate of implants inserted in the same patients was equal to 80.8%, with nine implants lost in 8 years. The survival analysis of the elements treated with both therapies was not statistically significant (p = .757) and the confidence interval was between 0.2455 and 2.777. CONCLUSION: In view of the superimposable results between the two therapies, it should be noted that the endodontically treated teeth could be interested by different pathologies while the restoration of the atrophic edentulous ridge with an implant support is predictable when patients comply with correct oral hygiene and when the occlusal loads are axially distributed in implant-protected occlusion. PMID- 22082011 TI - A national programme for mastitis control in Australia: Countdown Downunder. AB - In 1998, Countdown Downunder, Australia's national mastitis and cell count control programme, was created. With funding from the country's leading dairy organisation, Dairy Australia, this programme was originally intended to run for three years but is now in its tenth year. As it was the first time Australia had attempted a national approach to mastitis control on the farm, the first three years of the programme were largely concerned with the development of resources to be used by farmers and service providers. The second three years were devoted to training with both groups. Since that time, Countdown Downunder has entered into a second resource development phase. The goal of the programme was to achieve a reduction in the bulk milk somatic cell count from the Australian dairy herd. To achieve this, the programme had to develop resources with clear and consistent messages around mastitis and somatic cell count control on farms. It was determined that progress toward the goals would be made more rapidly if service providers were trained in the use of these resources prior to farmers. This paper reviews the Countdown Downunder programme from 1998 to 2007. PMID- 22082012 TI - Young and older adults' beliefs about effective ways to mitigate age-related memory decline. AB - This study investigated whether young and older adults vary in their beliefs about the impact of various mitigating factors on age-related memory decline. Eighty young (ages 18-23) and 80 older (ages 60-82) participants reported their beliefs about their own memory abilities and the strategies that they use in their everyday lives to attempt to control their memory. Participants also reported their beliefs about memory change with age for hypothetical target individuals who were described as using (or not using) various means to mitigate memory decline. There were no age differences in personal beliefs about control over current or future memory ability. However, the two age groups differed in the types of strategies they used in their everyday life to control their memory. Young adults were more likely to use internal memory strategies, whereas older adults were more likely to focus on cognitive exercise and maintaining physical health as ways to optimize their memory ability. There were no age differences in rated memory change across the life span in hypothetical individuals. Both young and older adults perceived strategies related to improving physical and cognitive health as effective means of mitigating memory loss with age, whereas internal memory strategies were perceived as less effective means for controlling age related memory decline. PMID- 22082013 TI - The effectiveness of updating metacognitive knowledge in the elderly: evidence from metamnemonic judgments of word frequency. AB - Accurate metacognitive knowledge is vital for optimal performance in self regulated learning. Yet older adults have deficiencies in implementing effective learning strategies and knowledge updating and consequently may not learn as effectively from task experience as younger adults. Here we assess the ability of older adults to update metacognitive knowledge about the effects of word frequency on recognition. Young adults have been shown to correct their misconceptions through experience with the task, but the greater difficulty older adults have with knowledge updating makes it unclear whether task experience will be sufficient for older adults. The performance of older adults in this experiment qualitatively replicates the results of a comparison group of younger subjects, indicating that both groups are able to correct their metacognitive knowledge through task experience. Older adults seem to possess more effective and flexible metacognition than sometimes suggested. PMID- 22082014 TI - Reading in healthy ageing: the influence of information structuring in sentences. AB - In three experiments, we investigated the cognitive effects of linguistic prominence to establish whether focus plays a similar or different role in modulating language processing in healthy ageing. Information structuring through the use of cleft sentences is known to increase the processing efficiency of anaphoric references to elements contained with a marked focus structure. It also protects these elements from becoming suppressed in the wake of subsequent information, suggesting selective mechanisms of enhancement and suppression. In Experiment 1 (using self-paced reading), we found that focus enhanced (faster) integration for anaphors referring to words contained within the scope of focus; but suppressed (slower) integration for anaphors to words contained outside of the scope of focus; and in some cases, the effects were larger in older adults. In Experiment 2 (using change detection), we showed that older adults relied more on the linguistic structure to enhance change detection when the changed word was in focus. In Experiment 3 (using delayed probe recognition and eye-tracking), we found that older adults recognized probes more accurately when they were made to elements within the scope of focus than when they were outside the scope of focus. These results indicate that older adults' ability to selectively attend or suppress concepts in a marked focus structure is preserved. PMID- 22082015 TI - Whoops, I did it again: commission errors in prospective memory. AB - Prospective memory research almost exclusively examines remembering to execute an intention, but the ability to forget completed intentions may be similarly important. We had younger and older adults perform a prospective memory task (press Q when you see corn or dancer) and then told them that the intention was completed. Participants later performed a lexical-decision task (Phase 2) in which the prospective memory cues reappeared. Initial prospective memory performance was similar between age groups, but older adults were more likely than younger adults to press Q during Phase 2 (i.e., commission errors). This study provides the first experimental demonstration of event-based prospective memory commission errors after all prospective memory tasks are finished and identifies multiple factors that increase risk for commission errors. PMID- 22082016 TI - Externalities from grain consumption: a survey. AB - The US Department of Agriculture (USDA) publishes their MyPyramid plan as a recommended eating model for all Americans. As part of this model, grain consumption is emphasized. This grain consumption has the potential to generate positive externalities, such as reduced rates of obesity, diabetes and other chronic diseases. Such positive externalities can potentially produce tangible economic benefits in terms of public health. In contrast, newer nutritional research shows that grain consumption may have negative effects on health for certain population groups. Celiac disease is four times as common as it was 50 years ago and is often under-diagnosed. Other population groups exhibit gluten sensitivity which can impact the development of asthma, allergies and neurological difficulties. This survey intends to provide a comprehensive description of both the positive and negative externalities associated with grain consumption and the resulting impact on human health. PMID- 22082017 TI - Yeast dynamin Vps1 and amphiphysin Rvs167 function together during endocytosis. AB - Dynamins are a conserved family of proteins involved in many membrane fusion and fission events. Previously, the dynamin-related protein Vps1 was shown to localize to endocytic sites, and yeast carrying deletions for genes encoding both the BAR domain protein Rvs167 and Vps1 had a more severe endocytic scission defect than either deletion alone. Vps1 and Rvs167 localize to endocytic sites at the onset of invagination and disassemble concomitant with inward vesicle movement. Rvs167-GFP localization is reduced in cells lacking vps1 suggesting that Vps1 influences Rvs167 association with the endocytic complex. Unlike classical dynamins, Vps1 does not have a proline-arginine domain that could interact with SH3 domain-containing proteins. Thus, while Rvs167 has an SH3 domain, it is not clear how an interaction would be mediated. Here, we demonstrate an interaction between Rvs167 SH3 domain and the single type I SH3 binding motif in Vps1. Mutant Vps1 that cannot bind Rvs167 rescues all membrane fusion/fission functions associated with Vps1 except for endocytic function, demonstrating the specificity and mechanistic importance of the interaction. In vitro, an Rvs161/Rvs167 heterodimer can disassemble Vps1 oligomers. Overall, the data support the idea that Vps1 and the amphiphysins function together to mediate scission during endocytosis in yeast. PMID- 22082018 TI - Multiscale photoacoustic microscopy of single-walled carbon nanotube-incorporated tissue engineering scaffolds. AB - Three-dimensional polymeric scaffolds provide structural support and function as substrates for cells and bioactive molecules necessary for tissue regeneration. Noninvasive real-time imaging of scaffolds and/or the process of tissue formation within the scaffold remains a challenge. Microcomputed tomography, the widely used technique to characterize polymeric scaffolds, shows poor contrast for scaffolds immersed in biological fluids, thereby limiting its utilities under physiological conditions. In this article, multiscale photoacoustic microscopy (PAM), consisting of both acoustic-resolution PAM (AR-PAM) and optical-resolution PAM (OR-PAM), was employed to image and characterize single-walled carbon nanotube (SWNT)-incorporated poly(lactic-co-glycolic acid) polymer scaffolds immersed in biological buffer. SWNTs were incorporated to reinforce the mechanical properties of the scaffolds, and to enhance the photoacoustic signal from the scaffolds. By choosing excitation wavelengths of 570 and 638 nm, multiscale PAM could spectroscopically differentiate the photoacoustic signals generated from blood and from carbon-nanotube-incorporated scaffolds. OR-PAM, providing a fine lateral resolution of 2.6 MUm with an adequate tissue penetration of 660 MUm, successfully quantified the average porosity and pore size of the scaffolds to be 86.5%+/-1.2% and 153+/-15 MUm in diameter, respectively. AR-PAM further extended the tissue penetration to 2 mm at the expense of lateral resolution (45 MUm). Our results suggest that PAM is a promising tool for noninvasive real-time imaging and monitoring of tissue engineering scaffolds in vitro, and in vivo under physiological conditions. PMID- 22082019 TI - Molecular characterization of novel TaNAC genes in wheat and overexpression of TaNAC2a confers drought tolerance in tobacco. AB - Plant-specific NAC (NAM/ATAF/CUC) transcription factors (TFs) have been reported to play a role in diverse stress responses and developmental processes. We show here that six new genes encoding NAC TFs in wheat (Triticum aestivum) were identified (named as TaNAC2a, TaNAC4a, TaNAC6, TaNAC7, TaNAC13 and TaNTL5, respectively), and we classified them into three groups: stress-related NACs, development-related NACs and NTLs (membrane-associated TFs belonging to NAC) by phylogenetic analysis. All TaNACs were induced by one or several kinds of stress treatments including dehydration, salinity and low temperature, whereas different genes showed different expression levels. All these TaNACs, except TaNAC7, were proven to have transcriptional activation activity in the yeast strain AH109 by transactivation analysis. Furthermore, subcellular localization analysis revealed that four TaNAC:GFP (green fluorescent protein) fusion proteins were localized in the nucleus, TaNAC2a:GFP mainly located in the nucleus and the plasma membrane, TaNTL5:GFP was associated with the membrane, while truncated TaNTL5(DeltaTM):GFP (lacking the transmembrane motif) was detected exclusively in the nucleus. Semi quantitative reverse transcription polymerase chain reaction analysis demonstrated that five genes exhibited organ-specific expression. Transgenic tobacco plants overexpressing TaNAC2a showed higher fresh weight and dry weight than non-transgenic plants under drought condition, which indicated that the transgene improved tobacco tolerance to drought treatment. Together, these results provided a preliminary characterization of six TaNACs, which possessed a potential role in improving stress tolerance and the regulation of development in wheat, and suggested that TaNAC2a was potentially useful for engineering drought tolerant plants. PMID- 22082020 TI - Leisure time emotional excitement increases endothelin-1 and interleukin-6 in cardiac patients. AB - OBJECTIVES. Emotional excitement may trigger serious cardiovascular (CV) events. Our objective was to compare the changes in potential surrogate markers of CV events in patients with coronary artery disease (CAD) during emotional excitement and exercise. DESIGN. Fifty-three enthusiastic ice-hockey spectators with stable CAD attended the Finnish national ice-hockey play-off matches and a maximal bicycle exercise. Plasma catecholamines, endothelin-1, interleukin-6, and markers of platelet activation and blood coagulation were determined before and during the match and before and after the exercise. RESULTS. Plasma endothelin-1 (2.82 +/- 0.21 vs. 2.94 +/- 0.25 pg/mL, p < 0.0001), noradrenaline (4.38 +/- 1.79 vs. 4.77 +/- 1.75 nmol/L, p = 0.009) and interleukin-6 (2.04 +/- 1.98 vs. 2.90 +/- 2.41 pg/mL, p < 0.0001) increased during the match, but markers of platelet activation and coagulation remained unchanged. Endothelin-1 did not change during exercise (2.73 +/- 0.17 vs. 2.72 +/- 0.19 pg/mL, p = 0.593) but noradrenaline (2.70 +/- 1.08 vs.10.6 +/- 5.5 nmol/L), adrenaline (0.23 +/- 0.13 vs. 0.52 +/- 0.37 nmol/L), interleukin-6 (1.77 +/- 1.59 vs. 2.43 +/- 1.78 pg/mL) and markers of platelet activation and blood coagulation increased significantly (p < 0.0001 for all). CONCLUSIONS. The responses of surrogate markers of acute CV events to emotional excitement and physical exercise are partly different. Emotional excitement causes concomitant increases in markers reflecting vulnerability to atherosclerotic plaque complications while physical exercise causes more prominent changes in markers of coagulation. PMID- 22082021 TI - The effect of cold application on pain due to chest tube removal. AB - AIM AND OBJECTIVES: The aim of the research is to determine the effect of cold application on the pain owing to chest tube removal for patients with single pleural chest tube. BACKGROUND: Removal of chest tubes causes patients to feel pain and interventions used for reducing the pain owing to the removal of chest tubes are not sufficient. DESIGN: Controlled clinical trial with repeated measures. METHODS: This study was conducted with 140 patients, of whom 70 patients were in the experimental group and 70 patients were in the control group, in a thoracic hospital in Turkey. Data were collected using a data collection form consisting of patients' demographic and health history and Visual Analogue Scale. Cold was applied to patients in the experimental group prior to chest tube removal. In the experimental group, skin temperature and pain intensity was measured for each patient at four time points. In the control group, pain intensity was evaluated for each patient at three time points. Data were evaluated using Chi-square and Repeated Measurements two-way anova tests. RESULTS: The Visual Analogue Scale score was measured immediately after the chest tube removal in the experimental group was 3.85, compared with 5.60 in the control group. There were significant differences on pain with cold application between the two groups prior and after the intervention. Age, gender, the number of days the chest tube was inserted and the chest tube insertion indication had no effect on the pain owing to chest tube removal. CONCLUSION: Cold application is effective in reducing the pain owing to chest tube removal. RELEVANCE TO CLINICAL PRACTICE: Cold application was recommended prior to chest tube removal to reduce the pain owing to removal of chest tube. PMID- 22082022 TI - Absorption of light in a single-nanowire silicon solar cell decorated with an octahedral silver nanocrystal. AB - In recent photovoltaic research, nanomaterials have offered two new approaches for trapping light within solar cells to increase their absorption: nanostructuring the absorbing semiconductor and using metallic nanostructures to couple light into the absorbing layer. This work combines these two approaches by decorating a single-nanowire silicon solar cell with an octahedral silver nanocrystal. Wavelength-dependent photocurrent measurements and finite-difference time domain simulations show that increases in photocurrent arise at wavelengths corresponding to the nanocrystal's surface plasmon resonances, while decreases occur at wavelengths corresponding to optical resonances of the nanowire. Scanning photocurrent mapping with submicrometer spatial resolution experimentally confirms that changes in the device's photocurrent come from the silver nanocrystal. These results demonstrate that understanding the interactions between nanoscale absorbers and plasmonic nanostructures is essential to optimizing the efficiency of nanostructured solar cells. PMID- 22082023 TI - Microbiologic characteristics and antimicrobial susceptibility of pacemaker/ICD infections: a moving target! PMID- 22082024 TI - Charge transport and glassy dynamics in ionic liquids. AB - Ionic liquids (ILs) exhibit unique features such as low melting points, low vapor pressures, wide liquidus temperature ranges, high thermal stability, high ionic conductivity, and wide electrochemical windows. As a result, they show promise for use in variety of applications: as reaction media, in batteries and supercapacitors, in solar and fuel cells, for electrochemical deposition of metals and semiconductors, for protein extraction and crystallization, and many others. Because of the ease with which they can be supercooled, ionic liquids offer new opportunities to investigate long-standing questions regarding the nature of the dynamic glass transition and its possible link to charge transport. Despite the significant steps achieved from experimental and theoretical studies, no generally accepted quantitative theory of dynamic glass transition to date has been capable of reproducing all the experimentally observed features. In this Account, we discuss recent studies of the interplay between charge transport and glassy dynamics in ionic liquids as investigated by a combination of several experimental techniques including broadband dielectric spectroscopy, pulsed field gradient nuclear magnetic resonance, dynamic mechanical spectroscopy, and differential scanning calorimetry. Based on Einstein-Smoluchowski relations, we use dielectric spectra of ionic liquids to determine diffusion coefficients in quantitative agreement with independent pulsed field gradient nuclear magnetic resonance measurements, but spanning a broader range of more than 10 orders of magnitude. This approach provides a novel opportunity to determine the electrical mobility and effective number density of charge carriers as well as their types of thermal activation from the measured dc conductivity separately. We also unravel the origin of the remarkable universality of charge transport in different classes of glass-forming ionic liquids. PMID- 22082025 TI - Near-infrared light-triggered dissociation of block copolymer micelles using upconverting nanoparticles. AB - We demonstrate a novel strategy enabling the use of a continuous-wave diode near infrared (NIR) laser to disrupt block copolymer (BCP) micelles and trigger the release of their "payloads". By encapsulating NaYF(4):TmYb upconverting nanoparticles (UCNPs) inside micelles of poly(ethylene oxide)-block-poly(4,5 dimethoxy-2-nitrobenzyl methacrylate) and exposing the micellar solution to 980 nm light, photons in the UV region are emitted by the UCNPs, which in turn are absorbed by o-nitrobenzyl groups on the micelle core-forming block, activating the photocleavage reaction and leading to the dissociation of BCP micelles and release of co-loaded hydrophobic species. Our strategy of using UCNPs as an internal UV or visible light source upon NIR light excitation represents a general and efficient method to circumvent the need for UV or visible light excitation that is a common drawback for light-responsive polymeric systems developed for potential biomedical applications. PMID- 22082026 TI - Experimental (IR/Raman and 1H/13C NMR) and theoretical (DFT) studies of the preferential conformations adopted by L-lactic acid oligomers and poly(L-lactic acid) homopolymer. AB - L-Lactic acid (L-LA) oligomers (up to the pentamer) were studied by three complementary approaches: vibrational (IR and Raman) and NMR ((1)H and (13)C) spectroscopies and DFT calculations. Vibrational and NMR spectra of L-LA oligomers and poly(L-lactic acid) (PLLA) homopolymer were recorded at room temperature and interpreted. Further insight into the structures (conformations) of the title systems was provided by theoretical B3LYP/6-311++G(d,p) studies. Calculated energies and computed vibrational and NMR spectra of the most stable conformers of L-LA oligomers, together with the experimental vibrational and NMR spectra, enabled the characterization of the preferred conformations adopted by PLLA chains. PMID- 22082027 TI - Expression of human protein S100A7 (psoriasin), preparation of antibody and application to human larynx squamous cell carcinoma. AB - BACKGROUND: Up-regulation of S100A7 (Psoriasin), a small calcium-binding protein, is associated with the development of several types of carcinomas, but its function and possibility to serve as a diagnostic or prognostic marker have not been fully defined. In order to prepare antibodies to the protein for immunohistochemical studies we produced the recombinant S100A7 protein in E. coli. mRNA extracted from human tracheal tumor tissue which was amplified by RT PCR to provide the region coding for the S100A7 gene. The amplified fragment was cloned in the vector pCR2.1-TOPO and sub-cloned in the expression vector pAE. The protein rS100A7 (His-tag) was expressed in E. coli BL21::DE3, purified by affinity chromatography on an Ni-NTA column, recovered in the 2.0 to 3.5 mg/mL range in culture medium, and used to produce a rabbit polyclonal antibody anti rS100A7 protein. The profile of this polyclonal antibody was evaluated in a tissue microarray. RESULTS: The rS100A7 (His-tag) protein was homogeneous by SDS PAGE and mass spectrometry and was used to produce an anti-recombinant S100A7 (His-tag) rabbit serum (polyclonal antibody anti-rS100A7). The molecular weight of rS100A7 (His-tag) protein determined by linear MALDI-TOF-MS was 12,655.91 Da. The theoretical mass calculated for the nonapeptide attached to the amino terminus is 12,653.26 Da (delta 2.65 Da). Immunostaining with the polyclonal anti rS100A7 protein generated showed reactivity with little or no background staining in head and neck squamous cell carcinoma cells, detecting S100A7 both in nucleus and cytoplasm. Lower levels of S100A7 were detected in non-neoplastic tissue. CONCLUSIONS: The polyclonal anti-rS100A7 antibody generated here yielded a good signal-to-noise contrast and should be useful for immunohistochemical detection of S100A7 protein. Its potential use for other epithelial lesions besides human larynx squamous cell carcinoma and non-neoplastic larynx should be explored in future. PMID- 22082028 TI - A preliminary characterization of the cytosolic glutathione transferase proteome from Drosophila melanogaster. AB - The cytosolic GST (glutathione transferase) superfamily has been annotated in the Drosophila melanogaster genome database. Of 36 genes, four undergo alternative splicing to yield a total of 41 GST proteins. In the present study, we have obtained the 41 transcripts encoding proteins by RT (reverse transcription)-PCR using RNA template from Drosophila S2 cells, an embryonic cell line. This observation suggests that all of the annotated DmGSTs (D. melanogaster GSTs) in the proteome are expressed in the late embryonic stages of D. melanogaster. To avoid confusion in naming these numerous DmGSTs, we have designated them following the universal GST nomenclature as well as previous designations that fit within this classification. Furthermore, in the cell line, we identified an apparent processed pseudogene, gste8, in addition to two isoforms from the Delta class that have been published previously. Only approximately one-third of the expressed DmGSTs could be purified by conventional GSH affinity chromatography. The diverse kinetic properties as well as physiological substrate specificity of the DmGSTs are such that each individual enzyme displayed a unique character even compared with members from the same class. PMID- 22082029 TI - Optimizing parameters for clinical-scale production of high IL-12 secreting dendritic cells pulsed with oxidized whole tumor cell lysate. AB - BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cell population for activating tumor-specific T cells. Due to the wide range of methods for generating DCs, there is no common protocol or defined set of criteria to validate the immunogenicity and function of DC vaccines. METHODS: Monocyte-derived DCs were generated during 4 days of culture with recombinant granulocyte-macrophage colony stimulating factor and interleukin-4, and pulsed with tumor lysate produced by hypochlorous acid oxidation of tumor cells. Different culture parameters for clinical-scale DC preparation were investigated, including: 1) culture media; 2) culture surface; 3) duration of activating DCs with lipopolysaccharide (LPS) and interferon (IFN)-gamma; 4) method of DC harvest; and 5) cryomedia and final DC product formulation. RESULTS: DCs cultured in CellGenix DC media containing 2% human AB serum expressed higher levels of maturation markers following lysate-loading and maturation compared to culturing with serum-free CellGenix DC media or AIM-V media, or 2% AB serum supplemented AIM-V media. NunclonTMDelta surface, but not Corning((r)) tissue-culture treated surface and Corning((r)) ultra-low attachment surface, were suitable for generating an optimal DC phenotype. Recombinant trypsin resulted in reduced major histocompatibility complex (MHC) Class I and II expression on mature lysate loaded DCs, however presentation of MHC Class I peptides by DCs was not impaired and cell viability was higher compared to cell scraping. Preservation of DCs with an infusible cryomedia containing Plasma-Lyte A, dextrose, sodium chloride injection, human serum albumin, and DMSO yielded higher cell viability compared to using human AB serum containing 10% DMSO. Finally, activating DCs for 16 hours with LPS and IFN-gamma stimulated robust mixed leukocyte reactions (MLRs), and high IL-12p70 production in vitro that continued for 24 hours after the cryopreserved DCs were thawed and replated in fresh media. CONCLUSIONS: This study examined criteria including DC phenotype, viability, IL-12p70 production and the ability to stimulate MLR as metrics of whole oxidized tumor lysate-pulsed DC immunogenicity and functionality. Development and optimization of this unique method is now being tested in a clinical trial of autologous oxidized tumor lysate-pulsed DC in clinical-scale in recurrent ovarian, primary peritoneal or fallopian tube cancer (NCT01132014). PMID- 22082030 TI - Lack of influence of extracellular polymeric substances (EPS) level on hydroxyl radical mediated disinfection of Escherichia coli. AB - Photolysis of nitrate, a prevalent constituent in agriculturally impacted waters, may influence pathogen attenuation in such systems through production of hydroxyl radical ((*)OH). This study focuses on the efficacy of (*)OH generated during nitrate photolysis in promoting E. coli die-off as a function of extracellular polymeric substances (EPS) coverage. EPS levels of four E. coli isolates were systematically altered through a sonication extraction method and photochemical batch experiments with a solar simulator examined isolate viability loss as a function of time in nitrate solutions. E. coli viability loss over time exhibited two regimes: an initial induction time, t(s), with little decay was followed by rapid exponential decay characterized by a first-order disinfection rate constant, k. Increasing steady-state (*)OH concentrations enhanced E. coli viability loss, increasing values of k and decreasing t(s) values, both of which were quantified with a multitarget bacterial disinfection model. Notably, at a given steady-state (*)OH concentration, values of t(s) and k were independent of EPS levels, nor did they vary among the different E. coli strains considered. Results herein show that while (*)OH generated via nitrate photolysis enhances rates of disinfection in surface water, the mechanism by which (*)OH kills E. coli is relatively insensitive to common bacterial variables. PMID- 22082031 TI - Computation of measures of effect size for neuroscience data sets. AB - The overwhelming majority of research in the neurosciences employs P-values stemming from tests of statistical significance to decide on the presence or absence of an effect of some treatment variable. Although a continuous variable, the P-value is commonly used to reach a dichotomous decision about the presence of an effect around an arbitrary criterion of 0.05. This analysis strategy is widely used, but has been heavily criticized in the past decades. To counter frequent misinterpretations of P-values, it has been advocated to complement or replace P-values with measures of effect size (MES). Many psychological, biological and medical journals now recommend reporting appropriate MES. One hindrance to the more frequent use of MES may be their scarcity in standard statistical software packages. Also, the arguably most widespread data analysis software in neuroscience, matlab, does not provide MES beyond correlation and receiver-operating characteristic analysis. Here we review the most common criticisms of significance testing and provide several examples from neuroscience where use of MES conveys insights not amenable through the use of P-values alone. We introduce an open-access matlab toolbox providing a wide range of MES to complement the frequently used types of hypothesis tests, such as t-tests and analysis of variance. The accompanying documentation provides calculation formulae, intuitive explanations and example calculations for each measure. The toolbox described is usable without sophisticated statistical knowledge and should be useful to neuroscientists wishing to enhance their repertoire of statistical reporting. PMID- 22082033 TI - Economic evaluation of duloxetine as a first-line treatment for painful diabetic peripheral neuropathy in Mexico. AB - OBJECTIVE: To perform an economic evaluation of duloxetine, pregabalin, and both branded and generic gabapentin for managing pain in patients with painful diabetic peripheral neuropathy (PDPN) in Mexico. RESEARCH DESIGN AND METHODS: The analysis was conducted using a 3-month decision model, which compares duloxetine 60 mg once daily (DUL), pregabalin 150 mg twice daily (PGB), and gabapentin 600 mg three-times daily (GBP) for PDPN patients with moderate-to-severe pain. A systematic review was performed and placebo-adjusted risk ratios for achieving good pain relief (GPR), adverse events (AE), and withdrawal owing to intolerable AE were calculated. Direct medical costs included drug acquisition and additional visits due to lack of efficacy (poor pain relief) or intolerable AE. Unit costs were taken from local sources. Adherence rates were used to estimate the expected drug costs. All costs are expressed in 2010 Mexican Pesos (MXN). Utility values drawn from published literature were applied to health states. The proportion of patients with GPR and quality-adjusted life years (QALY) were assessed. RESULTS: Branded-GBP was dominated by all the other options. PGB was more costly and less effective than DUL. Compared with branded-GBP and PGB, DUL led to savings of 1.01 and 1.74 million MXN (per 1000 patients). The incremental cost per QALY gained with DUL used instead of generic-GBP was $102 433 MXN. This amount is slightly lower than the estimated gross domestic product per capita in Mexico for 2010. During a second-order Monte Carlo simulation, DUL had the highest probability of being cost-effective (61%), followed by generic-GBP (25%) and PGB (14%). LIMITATIONS: Study limitations include a short timeframe and using data from different dosage schemes for GBP and PGB. CONCLUSIONS: This study suggests that DUL provides overall savings and better health outcomes compared with branded-GBP and PGB. Administering DUL rather than generic-GBP is a cost-effective intervention to manage PDPN in Mexico. PMID- 22082032 TI - Changing trends in mastitis. AB - The global dairy industry, the predominant pathogens causing mastitis, our understanding of mastitis pathogens and the host response to intramammary infection are changing rapidly. This paper aims to discuss changes in each of these aspects. Globalisation, energy demands, human population growth and climate change all affect the dairy industry. In many western countries, control programs for contagious mastitis have been in place for decades, resulting in a decrease in occurrence of Streptococcus agalactiae and Staphylococcus aureus mastitis and an increase in the relative impact of Streptococcus uberis and Escherichia coli mastitis. In some countries, Klebsiella spp. or Streptococcus dysgalactiae are appearing as important causes of mastitis. Differences between countries in legislation, veterinary and laboratory services and farmers' management practices affect the distribution and impact of mastitis pathogens. For pathogens that have traditionally been categorised as contagious, strain adaptation to human and bovine hosts has been recognised. For pathogens that are often categorised as environmental, strains causing transient and chronic infections are distinguished. The genetic basis underlying host adaptation and mechanisms of infection is being unravelled. Genomic information on pathogens and their hosts and improved knowledge of the host's innate and acquired immune responses to intramammary infections provide opportunities to expand our understanding of bovine mastitis. These developments will undoubtedly contribute to novel approaches to mastitis diagnostics and control. PMID- 22082034 TI - Lost in translation? Psychometric properties and construct validity of the English Essen Climate Evaluation Schema (EssenCES) social climate questionnaire. AB - The social climate of correctional (forensic) settings is likely to have a significant impact on the outcome of treatment and the overall functioning of these units. The Essen Climate Evaluation Schema (EssenCES) provides an objective way of measuring social climate that overcomes the content, length, and psychometric limitations of other measures. But the English translation of the EssenCES has yet to be sufficiently validated for use in forensic settings in the United Kingdom. The current study presents psychometric properties (factor structure and internal consistency) and an examination of construct validity with the English EssenCES. Satisfactory internal consistency was found for all EssenCES scales, and the expected three-factor structure was confirmed with both staff and residents and in prison and secure hospital settings using confirmatory factor analysis. Evidence to support construct validity was established using multilevel models, which showed statistically significant associations between scores on the EssenCES and scores on the Working Environment Scale, institutional aggression, and site security. Future validation work and potential practical applications of the EssenCES are discussed. PMID- 22082035 TI - The Unidimensional Relationship Closeness Scale (URCS): reliability and validity evidence for a new measure of relationship closeness. AB - A fundamental dimension along which all social and personal relationships vary is closeness. The Unidimensional Relationship Closeness Scale (URCS) is a 12-item self-report scale measuring the closeness of social and personal relationships. The reliability and validity of the URCS were assessed with college dating couples (N = 192), female friends and strangers (N = 330), friends (N = 170), and family members (N = 155). The results show that the scale is unidimensional, with high reliability across relationship types (M alpha = .96). Evidence consistent with validity included substantial within-couple agreement for the romantic couples (intraclass correlation = .41), substantial friend-stranger discrimination for the female friends (eta2 = .82), and measurement invariance across relationship types. Evidence of convergent and divergent validity was obtained for inclusion of other in the self and relational satisfaction, respectively. PMID- 22082036 TI - Do personality scale items function differently in people with high and low IQ? AB - Intelligence differences might contribute to true differences in personality traits. It is also possible that intelligence might contribute to differences in understanding and interpreting personality items. Previous studies have not distinguished clearly between these possibilities. Before it can be accepted that scale score differences actually reflect personality differences, personality items should show measurement invariance. The authors used item response theory to test measurement invariance in the five-factor model scales of the International Personality Item Pool (IPIP) and NEO-Five-Factor Inventory (NEO FFI) across two groups of participants from the Lothian Birth Cohort 1936 with relatively low and high cognitive abilities. Each group consisted of 320 individuals, with equal numbers of men and women. The mean IQ difference of the groups was 21 points. It was found that the IPIP and NEO-FFI items were measurement invariant across all five scales, making it possible to conclude that any differences in IPIP and NEO-FFI scores between people with low and high cognitive abilities reflected personality trait differences. PMID- 22082037 TI - Porcine-derived xenograft combined with a soft cortical membrane versus extraction alone for implant site development: a clinical study in humans. AB - BACKGROUND: An adequate alveolar crest is essential for implant placement in terms of esthetics and function. The objective of this randomized clinical trial was to compare the preservation of the alveolar ridge dimensions following tooth extraction using porcine-derived xenograft combined with a membrane versus extraction-alone (EXT) sites. METHODS: Fifteen patients who required double extraction of contralateral premolars and delayed implant placement were randomly selected to receive both ridge-preservation procedure and EXT. The test sites (alveolar ridge preservation [ARP]) included 15 sockets treated using a corticocancellous porcine bone xenograft (OsteoBiol(r) Gen-Os; Tecnoss srl, Giaveno, Italy) associated with a soft cortical membrane (OsteoBiol(r) Lamina; Tecnoss srl), while the corresponding control sites (EXT) were left without grafting for EXT. Horizontal and vertical ridge dimensions were recorded at baseline and 6 months after extractions. RESULTS: After 6 months, the EXT sites showed a significantly greater reabsorption of the buccolingual/palatal dimension of the alveolar ridge (3.7 +/- 1.2 mm) compared with the ARP sites (1.8 +/- 1.3 mm). The mean vertical ridge height reduction in the control sockets was 3.1 +/- 1.3 mm at the buccal sites and 2.4 +/- 1.6 mm at the lingual sites compared with 0.6 +/- 1.4 and 0.5 +/- 1.3 mm, respectively, in the test sockets. The differences between test and control sockets were not significant for the mesial and distal measurements. CONCLUSIONS: The placement of a porcine xenograft with a membrane in an extraction socket can be used to reduce the hard tissue reabsorption after tooth extraction compared with EXT. PMID- 22082038 TI - Skin surveillance intentions among family members of patients with melanoma. AB - BACKGROUND: First-degree relatives of individuals diagnosed with melanoma are at increased disease risk. However, many first-degree relatives do not receive a periodic total cutaneous examination from a health care provider or engage in regular skin self-examination. The goal of this study was to identify correlates of total cutaneous examination and skin self-examination intentions among first degree relatives of melanoma patients, thus providing insight on factors that should be targeted in future intervention research. METHODS: The participants were 545 first-degree relatives of melanoma patients at increased disease risk due to their risk factor profile and lack of skin surveillance behaviors. Participants completed a telephone survey regarding their total cutaneous examination and skin self-examination intentions and potential correlates, including demographics, medical factors, psychological factors, knowledge, and social influence factors. RESULTS: Intentions to receive a total cutaneous examination were higher among first-degree relatives with more education, those perceiving higher benefits and lower barriers to an examination, and those reporting greater physician and family support. Intentions to receive a skin self examination were higher among those with higher benefits and lower barriers to self-examination, and higher family support. CONCLUSIONS: Interventions to promote skin surveillance behaviors among first-degree relatives of melanoma patients should highlight the benefits of early detection of melanoma, address barriers to receipt of total cutaneous examination and engagement in skin self examination, and promote support from physicians and family members. PMID- 22082039 TI - Decellularized human cornea for reconstructing the corneal epithelium and anterior stroma. AB - In this project, we strived to develop a decellularized human cornea to use as a scaffold for reconstructing the corneal epithelium and anterior stroma. Human cadaver corneas were decellularized by five different methods, including detergent- and nondetergent-based approaches. The success of each method on the removal of cells from the cornea was investigated. The structural integrity of decellularized corneas was compared with the native cornea by electron microscopy. The integrity of the basement membrane of the epithelium was analyzed by histology and by the expression of collagen type IV, laminin, and fibronectin. Finally, the ability of the decellularized corneas to support the growth of human corneal epithelial cells and fibroblasts was assessed in vitro. Corneas processed using Triton X-100, liquid nitrogen, and poly(ethylene glycol) resulted in incomplete removal of cellular material. Corneas processed with the use of sodium dodecyl sulfate (SDS) or with sodium chloride (NaCl) plus nucleases successfully removed all cellular material; however, only the NaCl plus nuclease treatment kept the epithelial basement membrane completely intact. Corneas processed with NaCl plus nuclease supported both fibroblast and epithelial cell growth in vitro, while corneas treated with SDS supported the growth of only fibroblasts and not epithelial cells. Decellularized human corneas provide a scaffold that can support the growth of corneal epithelial cells and stromal fibroblasts. This approach may be useful for reconstructing the anterior cornea and limbus using autologous cells. PMID- 22082041 TI - High-performance graphene-based transparent flexible heaters. AB - We demonstrate high-performance, flexible, transparent heaters based on large scale graphene films synthesized by chemical vapor deposition on Cu foils. After multiple transfers and chemical doping processes, the graphene films show sheet resistance as low as ~43 Ohm/sq with ~89% optical transmittance, which are ideal as low-voltage transparent heaters. Time-dependent temperature profiles and heat distribution analyses show that the performance of graphene-based heaters is superior to that of conventional transparent heaters based on indium tin oxide. In addition, we confirmed that mechanical strain as high as ~4% did not substantially affect heater performance. Therefore, graphene-based, flexible, transparent heaters are expected to find uses in a broad range of applications, including automobile defogging/deicing systems and heatable smart windows. PMID- 22082040 TI - Functional polymorphisms in dopamine-related genes: effect on neurocognitive functioning in HIV+ adults. AB - Dopaminergic dysfunction is a putative mechanism underlying HIV-associated neurocognitive disorders. Dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) have been specifically implicated. We report analyses examining the main effects of functional polymorphisms within dopamine-modulating genes, as well as their interactive effects with disease severity, upon neurocognitive functioning in HIV+ adults. METHOD: A total of 184 HIV+ adults were included in the analysis. Three polymorphisms were examined within dopamine-modulating genes: COMT val158met, BDNF val66met, and the DAT 3' variable number tandem repeat. Separate hierarchical regression analyses for five neurocognitive domains (working memory, processing speed, learning, memory, motor) were conducted. Predictor variables were age, ethnicity, gender, education, CD4+ T-cell count, current depression, genotype, and an interaction term capturing genotype and disease severity (CD4). RESULTS: None of the polymorphisms or HIV disease variables significantly improved the hierarchical regression models. Younger age, higher education, and Caucasian ethnicity were almost invariably associated with better functioning across all five cognitive domains. A trend was noted for current depression as a predictor of motor and learning ability. CONCLUSION: This study did not find evidence to support direct or interactive effects of dopamine-related genes and HIV disease severity on neurocognitive functioning. PMID- 22082042 TI - Simultaneous existence of sustained double chamber tachycardias originating from the aortic sinus of Valsalva. AB - Monomorphic ventricular tachycardia is basically a benign phenomenon in patients without structural heart disease. The focal source of the tachycardia is usually located in the right ventricular outflow tract and more rarely in the left ventricular outflow tract. Aortic sinus of Valsalva (ASV) is a well-known source of atrial and ventricular tachycardias. We report a case with simultaneous existence of sustained atrial and ventricular tachycardias originating from ASV, which was successfully treated with radiofrequency catheter ablation. PMID- 22082043 TI - The effect of KCNJ11 polymorphism on the risk of type 2 diabetes: a global meta analysis based on 49 case-control studies. AB - Potassium inwardly rectifying channel, subfamily-J, member 11 (KCNJ11) gene encodes Kir6.2 subunits of the adenosine triphosphate (ATP)-sensitive potassium channel involved in glucose-mediated metabolic signaling pathway and has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) based on its function in glucose-stimulated insulin secretion. In the past decade, a number of case-control studies have been conducted to investigate the relationship between the KCNJ11 polymorphisms and T2D. However, these studies have yielded contradictory results. To investigate this inconsistency and derive a more precise estimation of the relationship, we conducted a comprehensive meta analysis of 64,403 cases and 122,945 controls from 49 published studies. Using the random-effects model, we found a significant association between E23K (rs5219) polymorphism and T2D risk with per-allele odds ratio of 1.13 (95% confidence interval: 1.10-1.15; p<10(-5)). Significant results were found in East Asians and Caucasians when stratified by ethnicity; whereas no significant associations were found among South Asians and other ethnic populations. In subgroup analysis by sample size, mean age and body mass index (BMI) of cases, mean BMI of controls and diagnostic criterion, significantly increased risks were found in all genetic models. This meta-analysis suggests that the E23K polymorphism in KCNJ11 is associated with elevated T2D risk, but these associations vary in different ethnic populations. PMID- 22082044 TI - Romiplostim efficacy in an acute myeloid leukemia patient with transfusion refractory thrombocytopenia. AB - BACKGROUND: Refractoriness to platelet (PLT) transfusion is a feared, life threatening complication in hematology-oncology patients. Despite increased PLT requirement and treatment costs, the clinical management is difficult and these patients had less favorable outcomes. CASE REPORT: We report on the efficacy of the thrombopoietic agent romiplostim in a patient with acute myeloid leukemia with chemotherapy-induced transfusion-refractory thrombocytopenia. CONCLUSION: Romiplostim could be very helpfull in the management of AML patients with transfusion refractory thrombocytopenia. PMID- 22082045 TI - Organogold clusters protected by phenylacetylene. AB - A new class of monolayer-protected Au clusters with Au-C covalent bonds (organogold clusters) was synthesized by ligating phenylacetylene (PhC=CH) to PVP stabilized Au clusters. Matrix-assisted laser desorption ionization mass spectrometry revealed for the first time a series of stable compositions of the organogold (Au:C(2)Ph) clusters. PMID- 22082046 TI - Consequences of butylated hydroxytoluene in the freezing extender on post-thaw characteristics of stallion spermatozoa in vitro. AB - Ejaculates from six pure Spanish stallions were split, and one subsample frozen in a commercial extender supplemented with the lipid soluble antioxidant butylated hydroxytoluene (BHT), while the other subsample served as control. After at least 4 weeks of storage, samples were thawed and post-thaw sperm quality analysed: sperm motility and kinematics using a CASA system, membrane and acrosome integrity and mitochondrial membrane potential using flow cytometry. The outcome of cryopreservation varied significantly among stallions. However, the supplementation with 1 mm BHT had no significant effect on any of the sperm parameters evaluated post-thaw. PMID- 22082048 TI - NADPH oxidase is involved in H2O2-induced differentiation of human promyelocytic leukaemia HL-60 cells. AB - The expression and activity of NADPH oxidase increase when HL-60 cells are induced into terminally differentiated cells. However, the function of NADPH oxidase in differentiation is not well elucidated. With 150-500 MUM H2O2 inducing differentiation of HL-60 cells, we measured phagocytosis of latex beads and investigated cell electrophoresis. Two inhibitors of NADPH oxidase, DPI (diphenyleneiodonium) and APO (apocynin), blocked the differentiation potential of cells induced by 200 MUM H2O2. However, H2O2 stimulated the generation of intracellular superoxide (O2*-), which decreased in the presence of the two inhibitors. DPI also inhibited H2O2-induced ERK (extracellular-signal-regulated kinase) activation, as detected by Western blotting. Furthermore, PD98059, the inhibitor of the ERK pathway, inhibited the differentiation of HL-60 cells induced by H2O2. This shows that H2O2 can activate NADPH oxidase, leading to O2*- production, followed by ERK activation and ultimately resulting in the differentiation of HL-60 cells. The data indicate that NADPH oxidase is an important cell signal regulating cell differentiation. PMID- 22082050 TI - Lulo cell line derived from Lutzomyia longipalpis (Diptera: Psychodidae): a novel model to assay Leishmania spp. and vector interaction. AB - BACKGROUND: Leishmania (Vianna) braziliensis, Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) chagasi are important parasites in the scenario of leishmaniasis in Brazil. During the life cycle of these parasites, the promastigote forms adhere to the midgut epithelial microvillii of phlebotomine insects to avoid being secreted along with digestive products. Lulo cells are a potential model that will help to understand the features of this adhesion phenomenon. Here, we analyze the interaction between Leishmania spp. promastigotes and Lulo cells in vitro, specifically focusing on adhesion events occurring between three Leishmania species and this cell line. METHODS: Confluent monolayers of Lulo cells were incubated with promastigotes and adhesion was assessed using both light microscopy and scanning electron microscopy. FINDINGS: The results indicate that species from the subgenera Leishmania and Viannia have great potential to adhere to Lulo cells. The highest adherence rate was observed for L. (L.) chagasi after 24 h of incubation with Lulo cells (27.3 +/- 1.8% of cells with adhered promastigotes), followed by L. (L.) amazonensis (16.0 +/- 0.7%) and L. (V.) braziliensis (3.0 +/- 0.7%), both after 48 h. In the ultrastructural analysis, promastigote adherence was also assessed by scanning electron microscopy, showing that, for parasites from both subgenera, adhesion occurs by both the body and the flagellum. The interaction of Lulo cells with Leishmania (L.) chagasi showed the participation of cytoplasmic projections from the former closely associating the parasites with the cells. CONCLUSIONS: We present evidence that Lulo cells can be useful in studies of insect-parasite interactions for Leishmania species. PMID- 22082051 TI - Salen-based coordination polymers of iron and the rare earth elements. AB - Reaction of N,N'-bis(4-carboxysalicylidene)ethylenediamine (H(4)L) with iron(III) chloride and lanthanide nitrates resulted in the coordination polymers of composition {[Ln(2)(FeLCl)(2)(NO(3))(2)(DMF)(5)].(DMF)(4)}(n) (Ln = Y, Eu, Gd, Tb, Dy). The polymers consist of iron-salen-based moieties having carboxylate linkers connected to rare earth atoms in a 1D chain structure. Thus, the iron salen complex acts as a "metalloligand". Because of the twisting of the chains, porous structures are formed and possess large free void space. The magnetic studies of selected compounds exhibit weak intramolecular antiferromagnetic interactions of Ln-Ln. At 3, 30, and 80 K, the Mossbauer spectra of the iron dysprosium compound show a strongly asymmetric quadrupole doublet with isomer shift and quadrupole splitting values typical for Fe(III) ions in high spin state. In addition, an anomalous temperature dependence of both isomer shift and quadrupole splitting has been observed. PMID- 22082049 TI - Multidimensional prognostic indices for use in COPD patient care. A systematic review. AB - BACKGROUND: A growing number of prognostic indices for chronic obstructive pulmonary disease (COPD) is developed for clinical use. Our aim is to identify, summarize and compare all published prognostic COPD indices, and to discuss their performance, usefulness and implementation in daily practice. METHODS: We performed a systematic literature search in both Pubmed and Embase up to September 2010. Selection criteria included primary publications of indices developed for stable COPD patients, that predict future outcome by a multidimensional scoring system, developed for and validated with COPD patients only. Two reviewers independently assessed the index quality using a structured screening form for systematically scoring prognostic studies. RESULTS: Of 7,028 articles screened, 13 studies comprising 15 indices were included. Only 1 index had been explored for its application in daily practice. We observed 21 different predictors and 7 prognostic outcomes, the latter reflecting mortality, hospitalization and exacerbation. Consistent strong predictors were FEV1 percentage predicted, age and dyspnoea. The quality of the studies underlying the indices varied between fairly poor and good. Statistical methods to assess the predictive abilities of the indices were heterogenic. They generally revealed moderate to good discrimination, when measured. LIMITATIONS: We focused on prognostic indices for stable disease only and, inevitably, quality judgment was prone to subjectivity. CONCLUSIONS: We identified 15 prognostic COPD indices. Although the prognostic performance of some of the indices has been validated, they all lack sufficient evidence for implementation. Whether or not the use of prognostic indices improves COPD disease management or patients' health is currently unknown; impact studies are required to establish this. PMID- 22082052 TI - Improvement on thermal performance of a disk-shaped miniature heat pipe with nanofluid. AB - The present study aims to investigate the effect of suspended nanoparticles in base fluids, namely nanofluids, on the thermal resistance of a disk-shaped miniature heat pipe [DMHP]. In this study, two types of nanoparticles, gold and carbon, in aqueous solution are used respectively. An experimental system was set up to measure the thermal resistance of the DMHP with both nanofluids and deionized [DI] water as the working medium. The measured results show that the thermal resistance of DMHP varies with the charge volume and the type of working medium. At the same charge volume, a significant reduction in thermal resistance of DMHP can be found if nanofluid is used instead of DI water. PMID- 22082053 TI - Genotypic diversity and spatial-temporal distribution of Symbiodinium clones in an abundant reef coral. AB - Genetic data are rapidly advancing our understanding of various biological systems including the ecology and evolution of coral-algal symbioses. The fine scale interactions between individual genotypes of host and symbiont remain largely unstudied and constitute a major gap in knowledge. By applying microsatellite markers developed for both host and symbiont, we investigated the intracolony diversity, prevalence and stability of Symbiodinium glynni (type D1) multilocus genotypes in association with dense populations of Pocillopora at two sites in the Gulf of California. The genetic diversity and allelic frequencies in reef populations of S. glynni remained stable over 3 years. Common clone genotypes persisted over this period, and no temporal population subdivision (Phi(PT) = 0.021 and -0.003) was detected. Collections from circular plots showed no statistical correlation between related Pocillopora individuals and their associations with particular S. glynni genotypes, with no spatial structuring or clonal aggregation across a reef for the symbiont. From permanent linear transects, samples were analysed from multiple locations within a colony and some were resampled approximately 1 year later. Many of these multisampled colonies (approximately 53%) were dominated by a single S. glynni genotype and tended to associate with the same symbiont genotype(s) over time, while colony ramets often possessed unrelated symbiont genotypes. In contrast to the species level, associations between genotypes of Pocillopora and S. glynni are apparently more flexible over space and time. The abundance of sexually recombinant genotypes of S. glynni combined with greater flexibility might provide adaptive mechanisms for these symbioses to evolve rapidly to changes in environmental conditions and allow particular symbiont genotypes to spread through a host population. PMID- 22082054 TI - Physical re-examination of parameters on a molecular collisions-based diffusion model for diffusivity prediction in polymers. AB - Molecular collisions, which are the microscopic origin of molecular diffusive motion, are affected by both the molecular surface area and the distance between molecules. Their product can be regarded as the free space around a penetrant molecule defined as the "shell-like free volume" and can be taken as a characteristic of molecular collisions. On the basis of this notion, a new diffusion theory has been developed. The model can predict molecular diffusivity in polymeric systems using only well-defined single-component parameters of molecular volume, molecular surface area, free volume, and pre-exponential factors. By consideration of the physical description of the model, the actual body moved and which neighbor molecules are collided with are the volume and the surface area of the penetrant molecular core. In the present study, a semiempirical quantum chemical calculation was used to calculate both of these parameters. The model and the newly developed parameters offer fairly good predictive ability. PMID- 22082055 TI - Design, synthesis, and incorporation of fluorous 5-methylcytosines into oligonucleotides. AB - A palladium-catalyzed Negishi coupling reaction has been developed to synthesize fluorous 5-methylcytosines. These fluorous nucleosides are incorporated into the oligonucleotides that correspond to part of the promoter region of Oct4, a master gene that undergoes dynamic DNA demethylation during cellular reprogramming. The separation of the fluorous oligonucleotides from its nonfluorous analogues has been achieved through solid-phase extraction over fluorous silica, suggesting its potential use in probing DNA demethylation. PMID- 22082056 TI - Implant survival rates after osteotome-mediated maxillary sinus augmentation: a systematic review. AB - PURPOSE: The aim of the present study was to systematically evaluate the implant survival rate after osteotome-mediated maxillary sinus augmentation with or without using grafting materials. MATERIALS AND METHODS: MEDLINE database was searched using a combination of specific search terms. Furthermore, a hand searching of the relevant journals and of the bibliographies of reviews was performed. Prospective and retrospective clinical studies with at least 20 patients treated by osteotome-mediated sinus floor elevation were included. RESULTS: Nineteen studies were selected for data analysis. A total of 1,822 patients, accounting for 3,131 implants were considered. Mean weighted cumulative implant survival at 1, 2, 3, and 5 years was estimated as 98.12%, 97.40%, 96.75%, and 95.81%, respectively. No significant difference was found in relation to the use of grafting material nor in relation to implant length. Overall implant survival was 92.7% for 331 implants placed in <5 mm ridge height and 96.9% for 2,525 implants inserted in >= 5 mm ridge height. The difference was significant (p = .0003). CONCLUSIONS: The transalveolar sinus augmentation technique could be a viable treatment in case of localized atrophy in the posterior maxilla even in case of minimal residual bone height. The prognosis can be more favorable when the residual ridge is at least 5 mm high. PMID- 22082057 TI - The infection of bad company: stigma by association. AB - Stigma by association represents the process through which the companions of stigmatized persons are discredited. Conduits for stigma by association range from the strong and enduring bonds of kinship to the arbitrary occasions of being seen in the company of someone who is stigmatized. A theoretical model is proposed in which both deliberative and spontaneous processes result in the spread of stigma to the companions of stigmatized persons. Support for this model was found across 3 studies that examined how explicit and implicit stigma relevant attitudes moderate stigma-by-association effects. When social relationships were meaningful (e.g., kinship), both explicit and implicit attitudes moderated the devaluation of stigmatized persons' companions. On the other hand, when social relationships appeared coincidental only implicit attitudes moderated companion devaluation. PMID- 22082058 TI - Chronic threat and contingent belonging: protective benefits of values affirmation on identity development. AB - Two longitudinal field experiments in a middle school examined how a brief "values affirmation" affects students' psychological experience and the relationship between psychological experience and environmental threat over 2 years. Together these studies suggest that values affirmations insulate individuals' sense of belonging from environmental threat during a key developmental transition. Study 1 provided an analysis of new data from a previously reported study. African American students in the control condition felt a decreasing sense of belonging during middle school, with low-performing students dropping more in 7th grade and high-performing students dropping more in 8th grade. The affirmation reduced this decline for both groups. Consistent with the notion that affirmation insulates belonging from environmental threat, affirmed African American students' sense of belonging in Study 1 fluctuated less over 2 years and became less contingent on academic performance. Based on the idea that developmentally sensitive interventions can have long-lasting benefits, Study 2 showed that the affirmation intervention was more effective if delivered before any drop in performance and subsequent psychological toll could unfold. The role of identity threat and affirmation in affecting the encoding of social experience, and the corresponding importance of timing treatments to developmentally sensitive periods, are explored. PMID- 22082059 TI - Control deprivation and styles of thinking. AB - Westerners habitually think in analytical ways, whereas East Asians tend to favor holistic styles of thinking. We replicated this difference but showed that it disappeared after control deprivation (Experiment 1). Brief experiences of control deprivation, which stimulate increased desire for control, caused Chinese participants to shift toward Western-style analytical thinking in multiple ways (Experiments 2-5). Western Caucasian participants also increased their use of analytical thinking after control deprivation (Experiment 6). Manipulations that required Chinese participants to think in Western, analytical ways caused their sense of personal control to increase (Experiments 7-9). Prolonged experiences of control deprivation, which past work suggested foster an attitude more akin to learned helplessness than striving for control, had the opposite effect of causing Chinese participants to shift back toward a strongly holistic style of thinking (Experiments 10-12). Taken together, the results support the reality of cultural differences in cognition but also the cross-cultural similarity of using analytical thinking when seeking to enhance personal control. PMID- 22082060 TI - Fundamental(ist) attribution error: Protestants are dispositionally focused. AB - Attribution theory has long enjoyed a prominent role in social psychological research, yet religious influences on attribution have not been well studied. We theorized and tested the hypothesis that Protestants would endorse internal attributions to a greater extent than would Catholics, because Protestantism focuses on the inward condition of the soul. In Study 1, Protestants made more internal, but not external, attributions than did Catholics. This effect survived controlling for Protestant work ethic, need for structure, and intrinsic and extrinsic religiosity. Study 2 showed that the Protestant-Catholic difference in internal attributions was significantly mediated by Protestants' greater belief in a soul. In Study 3, priming religion increased belief in a soul for Protestants but not for Catholics. Finally, Study 4 found that experimentally strengthening belief in a soul increased dispositional attributions among Protestants but did not change situational attributions. These studies expand the understanding of cultural differences in attributions by demonstrating a distinct effect of religion on dispositional attributions. PMID- 22082061 TI - Sensitive maintenance: a cognitive process underlying individual differences in memory for threatening information. AB - Dispositional styles of coping with threat influence memory for threatening information. In particular, sensitizers excel over repressors in their memory for threatening information after long retention intervals, but not after short ones. We therefore suggested that sensitizers, but not repressors, employ active maintenance processes during the retention interval to selectively retain threatening material. Sensitive maintenance was studied in 2 experiments in which participants were briefly exposed to threatening and nonthreatening pictures (Experiment 1, N = 128) or words (Experiment 2, N = 145). Following, we administered unannounced recognition tests before and after an intervening task that generated either high or low cognitive load, assuming that high cognitive load would impede sensitizers' memory maintenance of threatening material. Supporting our hypotheses, the same pattern of results was obtained in both experiments: Under low cognitive load, sensitizers forgot less threat material than repressors did; no such differences were observed under high cognitive load. PMID- 22082062 TI - Negative moods and the motivated remembering of past selves: the role of implicit theories of personal stability. AB - This research program explored how the positivity of people's memories of their past personal attributes is influenced by their desire to cope with negative mood states. The studies tested the hypothesis that beliefs and motives regarding the stability of personality will determine whether people idealize or derogate their earlier attributes in an attempt to repair distressing feelings. When knowledge structures or motives implying personal change are activated, people should derogate their past selves in response to negative moods; in contrast, when these factors imply personal stability, people should idealize their past selves in response to negative moods. Studies 1-3, which assessed the impact of mood negativity (neutral vs. negative) and theories (or motives) regarding personal change (change vs. stability) on the positivity of people's memories of their past attributes, supported this reasoning. Study 4 extended these findings by examining how an underlying mediating variable--mood-repair motivation--guides the effect of negative moods on recall of past selves. Implications of the results for research on temporal comparison, mood-congruent recall, and posttraumatic growth are discussed. PMID- 22082063 TI - Purple corn (Zea mays L.) phenolic compounds profile and its assessment as an agent against oxidative stress in isolated mouse organs. AB - This study was designed to determine the contents of total polyphenols, flavonoids, flavonols, flavanols, and anthocyanins of purple corn (Zea mays L.) extracts obtained with different methanol:water concentrations, acidified with 1% HCl (1 N). Another objective was to determine the antioxidant activity by 1,1 diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and deoxyribose assay, individual phenolic compounds by high-performance liquid chromatography (HPLC), and endogenous antioxidant enzyme (superoxide dismutase [SOD], catalase [CAT], and total peroxidase [TPX]) activity and lipid peroxidation activity (thiobarbituric acid-reactive substances [TBARS] assay) in isolated mouse organs. Overall, the highest total content of polyphenols, anthocyanins, flavonoids, flavonols, and flavanols was obtained with the 80:20 methanol:water extract, acidified with 1% HCl (1 N). The 50% inhibitory concentration values obtained by the DPPH and ABTS assays with this extract were 66.3 MUg/mL and 250 MUg/mL, respectively. The antioxidant activity by the FRAP assay was 26.1 MUM Trolox equivalents/g, whereas the deoxyribose assay presented 93.6% inhibition. Because of these results, the 80:20 methanol:water extract, acidified with 1% HCl (1 N), was used for the remaining tests. Eight phenolic compounds were identified by HPLC: chlorogenic acid, caffeic acid, rutin, ferulic acid, morin, quercetin, naringenin, and kaempferol. Furthermore, it was observed that the purple corn extract was capable of significantly reducing lipid peroxidation (lower malondialdehyde [MDA] concentrations by the TBARS assay) and at the same time increasing endogenous antioxidant enzyme (CAT, TPX, and SOD) activities in isolated mouse kidney, liver, and brain. On the basis of the results, it was concluded that the purple corn extract contained various bioactive phenolic compounds that exhibited considerable in vitro antioxidant activity, which correlated well with the decreased MDA formation and increase in activity of endogenous antioxidant enzymes observed in the isolated mouse organs. This warrants further in vivo studies with purple corn extracts to assess its antioxidant activity and other bioactivities. PMID- 22082064 TI - Anti-inflammatory effects of methanol extract of Codium fragile in lipopolysaccharide-stimulated RAW 264.7 cells. AB - The methanol extract of Codium fragile (MECF) has been reported to possess bioactive properties such as antidegranulation in eosinophils, as well as anti edema, antibacterial, and antiviral activities. However, little is known about the molecular effects of MECF on lipopolysaccharide (LPS)-induced inflammation. Therefore, we investigated whether MECF affects the expression of inflammatory mediators in LPS-stimulated RAW 264.7 cells. To evaluate the anti-inflammatory effects of MECF, the cells were pretreated with MECF for 1 hour and then cultured with LPS for 24 hours. Our results indicate that MECF significantly attenuated secretion of LPS-induced inflammatory mediators nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor (TNF)-alpha in RAW 264.7 cells. Additionally, LPS-induced mRNA and protein expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-alpha was decreased by pretreatment with MECF. These data indicate that MECF attenuates the expression of these inflammatory mediators at the transcriptional level. Therefore, we also investigated the effects of MECF on nuclear factor-kappaB (NF-kappaB) activity, which may be an important transcriptional factor for regulating the expression of iNOS, COX-2, and TNF-alpha mRNA. Our results showed that MECF reduced LPS-induced NF-kappaB activity via the suppression of nuclear translocation of the p50 and p65 NF-kappaB subunits and degradation of inhibitor of kappaB. In conclusion, we propose that MECF treatment down-regulates the expression and secretion of LPS induced inflammatory mediators by inhibiting NF-kappaB activity. PMID- 22082065 TI - Improved endothelial dysfunction by Cynanchum wilfordii in apolipoprotein E(-/-) mice fed a high fat/cholesterol diet. AB - Cynanchum wilfordii is used in traditional Chinese medicine with almost all parts of this plant considered beneficial for various vascular diseases. This study was performed to evaluate the effect of an ethanol extract of C. wilfordii (ECW) on vascular dysfunction in apolipoprotein E (apoE)(-/-) mice fed with high fat/cholesterol diets (HFCDs). The apoE(-/-) mice were fed HFCD consisting of 7.5% cocoa butter and 1.25% cholesterol, with or without 100 or 200 mg/day/kg ECW. Chronic ECW treatment significantly lessened the level of low-density lipoprotein (P<.05) and elevated that of high-density lipoprotein-cholesterol (P<.01). Chronic ECW treatment normalized the HFCD-induced increase in systolic blood pressure, maintained smooth and soft intimal endothelial layers, and decreased intima-media thickness in aortic sections of HFCD-fed apoE(-/-) mice. ECW significantly restored the diet-induced decrease in vasorelaxation response to acetylcholine; however, the response to sodium nitroprusside did not change. ECW clearly restored the HFCD-induced reduction in endothelial nitric oxide synthase expression levels in aortic tissue, leading to decreased vascular inflammation through an inhibition of cellular adhesion molecules such as E selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule 1 as well as endothelin-1 (ET-1) expression. In conclusion, ECW ameliorates endothelial dysfunction via improvement of the nitric oxide/cyclic GMP signaling pathway in a diet/genetic model of hyperlipidemia. ECW also substantially inhibited the development of atherosclerosis, possibly by inhibiting ET-1, cell adhesion molecules, and lesion formation, suggesting a vascular protective role for this herb in the treatment and prevention of atherosclerotic vascular disease. PMID- 22082066 TI - Inhibition of adhesion of uropathogenic Escherichia coli bacteria to uroepithelial cells by extracts from cranberry. AB - Cranberry extract has been reported as a therapeutic agent, mainly in urinary tract infections due to its anti-adhesive capacity. In order to compare the effects of proanthocyanidin (procyanidin) (PAC)-standardized cranberry extracts and commercial PAC A2, we first investigated the presence of genes encoding known adhesins on 13 strains of uropathogenic strains coming from patients with cystisis. After this characterization, the anti-adhesive effects of PAC A2 were assayed on selected uropathogenic Escherichia coli strains before testing cranberry extracts. Before checking inhibitory effect on bacterial adhesion to cells, we showed that neither PAC A2 or three cranberry extracts (A, B, and C) specifically inhibited the growth and did not supply any potential nutrient to E. coli strains, including the unrelated control strain. PAC A2 exhibited an inhibitory effect on the adhesion of two selected uropathogenic strains of E. coli. This work also showed that a preliminary exposure of bacteria to PAC A2 significantly reduced the adhesion. This phenomenon has been also observed with a lesser impact when uroepithelial cells were pretreated with PAC A2. Moreover, the assays were more robust when bacteria were in fast growing conditions (exponential phase): the adhesion to uroepithelial cells was greater. Significant reduction of adhesion to urepithelial cells was observed: around 80% of inhibition of adhesion with the cranberry extracts at equivalent PAC concentration of 50 MUg/mL. The effects of the different assayed extracts were not obviously different except for extract B, which inhibited approximately 55% of adhesion at an equivalent PAC concentration of 5 MUg/mL. PMID- 22082067 TI - Doenjang, a fermented soybean paste, decreased visceral fat accumulation and adipocyte size in rats fed with high fat diet more effectively than nonfermented soybeans. AB - Soybean is known to have an anti-obesity effect. We compared the anti-obesity effect of doenjang, a fermented soybean paste, with that of nonfermented soybeans in rats. Steamed soybeans and doenjang (steamed soybeans fermented and aged for 10 months) were sampled and freeze-dried. Male Sprague-Dawley rats were fed basal (BA) (5% fat), high fat (HF) (30% fat), HF+steamed soybeans (SOY), or HF+doenjang (DJ) diet ad libitum for 8 weeks. HF significantly increased body weight gain, liver weight, hepatic triglyceride (TG) and cholesterol levels, and epididymal fat pad weight compared with BA. Compared with HF, body weight gain and hepatic TG and cholesterol levels were significantly lower in SOY and DJ groups, but they were not significantly different from each other. DJ significantly reduced visceral fat weight and epididymal adipocyte size compared with HF, whereas SOY resulted in a mild reduction without significance. This was possibly because DJ showed lowered fatty acid synthase (FAS) activity and elevated carnitine palmitoyltransferase (CPT)-1 activity in liver tissue more than SOY. SOY and DJ did not affect serum total and high-density lipoprotein-cholesterol levels compared with HF; however, DJ significantly lowered the atherogenic index and serum leptin level. In conclusion, doenjang, a fermented soybean product, was more effective than soybeans for preventing diet-induced visceral fat accumulation, possibly because of its greater effects on CPT-1 activity stimulation and FAS activity suppression. These effects may be due in part to the higher content of aglycone isoflavones in doenjang. PMID- 22082068 TI - Antihypertensive and cardioprotective effects of pumpkin seed oil. AB - Pumpkin seed oil is a natural product commonly used in folk medicine for treatment of prostatic hypertrophy. In the present study, the effects of treatment with pumpkin seed oil on hypertension induced by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg /kg/day) in rats were studied and compared with those of the calcium channel blocker amlodipine. Pumpkin seed oil (40 or 100 mg/kg), amlodipine (0.9 mg/kg), or vehicle (control) was given once daily orally for 6 weeks. Arterial blood pressure (BP), heart rate, electrocardiogram (ECG) changes, levels of serum nitric oxide (NO) (the concentrations of nitrite/nitrate), plasma malondialdehyde (MDA), blood glutathione, and erythrocytic superoxide dismutase activity were measured. Histopathological examination of heart and aorta was conducted as well. L-NAME administration resulted in a significant increase in BP starting from the second week. Pumpkin seed oil or amlodipine treatment significantly reduced the elevation in BP by L-NAME and normalized the L-NAME-induced ECG changes-namely, prolongation of the RR interval, increased P wave duration, and ST elevation. Both treatments significantly decreased the elevated levels of MDA and reversed the decreased levels of NO metabolites to near normal values compared with the L NAME-treated group. Amlodipine also significantly increased blood glutathione content compared with normal (but not L-NAME-treated) rats. Pumpkin seed oil as well as amlodipine treatment protected against pathological alterations in heart and aorta induced by L-NAME. In conclusion, this study has shown that pumpkin seed oil exhibits an antihypertensive and cardioprotective effects through a mechanism that may involve generation of NO. PMID- 22082069 TI - Modifying effects of lemongrass essential oil on specific tissue response to the carcinogen N-methyl-N-nitrosurea in female BALB/c mice. AB - Lemongrass (Cymbopogon citratus Stapf) essential oil has been used worldwide because of its ethnobotanical and medicinal usefulness. Regarding its medicinal usefulness, the present study evaluated the beneficial effects of lemongrass essential oil (LGEO) oral treatment on cell proliferation and apoptosis events and on early development of hyperplastic lesions in the mammary gland, colon, and urinary bladder induced by N-methyl-N-nitrosourea (MNU) in female BALB/c mice. The animals were allocated into three groups: G1, treated with LGEO vehicle for 5 weeks (five times per week); G2, treated with LGEO vehicle as for G1 and MNU (two injections each of 30 mg/kg of body weight at weeks 3 and 5); and G3, treated with LGEO (five times each with 500 mg/kg of body weight per week) and MNU as for G2. Twenty-four hours after the last MNU application, all animals were euthanized, and mammary glands, colon, and urinary bladder were collected for histological and immunohistochemical analysis. LGEO oral treatment significantly changed the indexes of apoptosis and/or cellular proliferation for the tissues analyzed. In particular, the treatment reduced the incidence of hyperplastic lesions and increased apoptosis in mammary epithelial cells. This increment in the apoptosis response may be related to a favorable balance in Bcl-2/Bax immunoreactivity in mammary epithelial cells. These findings indicate that LGEO presented a protective role against early MNU-induced mammary gland alterations in BALB/c mice. PMID- 22082070 TI - Micromarrows--three-dimensional coculture of hematopoietic stem cells and mesenchymal stromal cells. AB - Hematopoietic stem cell (HSC) transplant is a well established curative therapy for some hematological malignancies. However, achieving adequate supply of HSC from some donor tissues can limit both its application and ultimate efficacy. The theory that this limitation could be overcome by expanding the HSC population before transplantation has motivated numerous laboratories to develop ex vivo expansion processes. Pioneering work in this field utilized stromal cells as support cells in cocultures with HSC to mimic the HSC niche. We hypothesized that through translation of this classic coculture system to a three-dimensional (3D) structure we could better replicate the niche environment and in turn enhance HSC expansion. Herein we describe a novel high-throughput 3D coculture system where murine-derived HSC can be cocultured with mesenchymal stem/stromal cells (MSC) in 3D microaggregates--which we term "micromarrows." Micromarrows were formed using surface modified microwells and their ability to support HSC expansion was compared to classic two-dimensional (2D) cocultures. While both 2D and 3D systems provide only a modest total cell expansion in the minimally supplemented medium, the micromarrow system supported the expansion of approximately twice as many HSC candidates as the 2D controls. Histology revealed that at day 7, the majority of bound hematopoietic cells reside in the outer layers of the aggregate. Quantitative polymerase chain reaction demonstrates that MSC maintained in 3D aggregates express significantly higher levels of key hematopoietic niche factors relative to their 2D equivalents. Thus, we propose that the micromarrow platform represents a promising first step toward a high-throughput HSC 3D coculture system that may enable in vitro HSC niche recapitulation and subsequent extensive in vitro HSC self-renewal. PMID- 22082071 TI - Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation. AB - BACKGROUND: Many factors have been put forward as a driving mechanism of surgery triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions. METHODS: A prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO2 insufflation at the 10 cm of water. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale. Statistical analysis was performed by the non-parametric t test and two way ANOVA using Bonferroni post-tests. RESULTS: More pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24th and 72nd; p < 0.01--120th and p < 0.001--168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 +/- 33.63) was observed after OS in comparison with LS (20.31 +/- 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group. CONCLUSIONS: MIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences. CO2 insufflation however, led to moderate inflammation and less adhesion formation. PMID- 22082072 TI - Improving the United States airline industry's capacity to provide safe and dignified services to travelers with disabilities: focus group findings. AB - PURPOSE: As a component of a training development project for intercity air travel providers, we investigated the capacity of the airline industry to meet the needs of travelers with disabilities by exploring: (1) the level of sensitivity among personnel to travelers' needs, (2) training currently provided, (3) areas in which additional training might be beneficial, and (4) organisational/systems-level commitment to dignified assistance to all travelers. METHOD: Forty-four airline/vendor employees participated in nine focus groups in four US cities. Groups were audio recorded and transcribed. A grounded-theory approach was used to develop a coding system which was then applied to transcripts to identify themes. RESULTS: Factors influencing capacity grouped broadly into four areas: characteristics of the job/system, characteristics of current training, characteristics of providers themselves, and characteristics of travelers. At an interpersonal level, providers were empathetic and desired to provide dignified services. They lacked training and adequate equipment in some cases, however, and organisational commitment varied between companies. Traveler characteristics were also shown to impact service delivery. CONCLUSIONS: Results are promising but additional regulatory and organisational policies are needed to ensure quality services. Providers and consumers of intercity air travel services may benefit from the findings and recommendations of this study. PMID- 22082073 TI - Family members' report on speech-language pathology and community services for persons with aphasia in Hong Kong. AB - PURPOSE: This study investigates (a) the provision of speech-language pathology (SLP) services and community resources in Hong Kong for persons with aphasia (PWA) and their families and (b) family members' perception of the service quality. METHODS: A self-administered 42-item questionnaire was distributed in two community support groups. The questions included information on the demography data of the PWAs, details of the SLP services and family members' perception of PWAs' satisfaction with the hospital-based services and resources in community support groups. RESULTS: Results from 37 completed questionnaires indicated most inpatient and outpatient SLP sessions were delivered weekly and monthly, respectively, in fewer than 30 min. The primary foci of these sessions were assessment and treatment of aphasia. While professional SLP services were unavailable in support groups, the activities attended most frequently by the PWAs and their families were communication groups and social gatherings, respectively. Overall satisfaction was highest with support groups, followed by hospital-based inpatient and outpatient services. CONCLUSIONS: The results provide commentary on the existing practices of post-stroke aphasia management in Hong Kong, and will provide new insights into the clinical care of the PWAs and their families. Such knowledge can allow better planning of resource and manpower allocation for aphasia rehabilitation. PMID- 22082074 TI - Feed-forward neural network assisted by discriminant analysis for the spectroscopic discriminantion of cracked spores Ganoderma lucidum: A prospective biotechnology production tool. AB - A major problem for manufacturers of cracked spores Ganoderma lucidum, a traditional functional food/Chinese medicine (TCM), is to ensure that raw materials are consistent as received from the producer. To address this, a feed forward artificial neural network (ANN) method assisted by linear discriminant analysis (LDA) and principal component analysis (PCA) was developed for the spectroscopic discrimination of cracked spores of Ganoderma lucidum from uncracked spores. 120 samples comprising cracked spores, uncracked spores and concentrate of Ganoderma lucidum were analyzed. Differences in the absorption spectra located at nu1 (1143 - 1037 cm-1), nu2 (1660 - 1560 cm-1), nu3 (1745 - 1716 cm-1) and nu4 (2845 - 2798 cm-1) were identified by applying fourier transform infra-red (FTIR) spectroscopy and used as variables for discriminant analysis. The utilization of spectra frequencies offered maximum chemical information provided by the absorption spectra. Uncracked spores gave rise to characteristic spectrum that permitted discrimination from its cracked physical state. Parallel application of variables derived from unsupervised LDA/PCA provided useful (feed-forward) information to achieve 100% classification integrity objective in ANN. 100% model validation was obtained by utilizing 30 independent samples. nu1 was used to construct the matrix-matched calibration curve (n = 10) based on 4 levels of concentration (20%, 40%, 60% and 80% uncracked spores in cracked spores). A coefficient of correlation (r) of 0.97 was obtained. Relative standard deviation (RSD) of 11% was achieved using 100% uncracked spores (n = 30). These results demonstrate the feasibility of utilizing a combination of spectroscopy and prospective statistical tools to perform non destructive food quality assessment in a high throughput environment. PMID- 22082075 TI - Interventricular septal mass in a patient with cardiac sarcoidosis. AB - Sarcoidosis is a granulomatous disease that may involve multiple organ systems. The prognosis of sarcoidosis is influenced by the presence and severity of cardiac lesions. Thinning of the wall in the ventricular septum has often been reported, whereas an interventricular septal mass is rare. We describe a case of cardiac sarcoidosis resulting in a myocardial mass in the basal portion of the interventricular septum that was sensitive to corticosteroid treatment. PMID- 22082076 TI - Porous one-dimensional nanostructures through confined cooperative self-assembly. AB - We report a simple confined self-assembly process to synthesize nanoporous one dimensional photoactive nanostructures. Through surfactant-assisted cooperative interactions (e.g., pi-pi stacking, ligand coordination, and so forth) of the macrocyclic building block, zinc meso-tetra (4-pyridyl) porphyrin (ZnTPyP), self assembled ZnTPyP nanowires and nanorods with controlled diameters and aspect ratios are prepared. Electron microscopy characterization in combination with X ray diffraction and gas sorption experiments indicate that these materials exhibit stable single-crystalline and high surface area nanoporous frameworks with well-defined external morphology. Optical characterizations using UV-vis spectroscopy and fluorescence imaging and spectroscopy show enhanced collective optical properties over the individual chromophores (ZnTPyP), favorable for exciton formation and transport. PMID- 22082077 TI - Review: unchained maladie - a reassessment of the role of Ubb(+1) -capped polyubiquitin chains in Alzheimer's disease. AB - Molecular misreading allows the formation of mutant proteins in the absence of gene mutations. A mechanism has been proposed by which a frameshift mutant of the ubiquitin protein, Ubb(+1) , which accumulates in an age-dependent manner as a result of molecular misreading, contributes to neuropathology in Alzheimer's disease (Lam et al. 2000). Specifically, in the Ubb(+1) -mediated proteasome inhibition hypothesis Ubb(+1) 'caps' unanchored (that is, nonsubstrate linked) polyubiquitin chains, which then act as dominant inhibitors of the 26S proteasome. A review of subsequent literature indicates that this original hypothesis is broadly supported, and offers new insights into the mechanisms accounting for the age-dependent accumulation of Ubb(+1) , and how Ubb(+1) mediated proteasome inhibition may contribute to Alzheimer's disease. Further, recent studies have highlighted a physiological role for free endogenous unanchored polyubiquitin chains in the direct activation of certain protein kinases. This raises the possibility that Ubb(+1) -capped unanchored polyubiquitin chains could also exert harmful effects through the aberrant activation of tau or other ubiquitin-dependent kinases, neuronal NF-kappaB activity or NF-kappaB-mediated neuroinflammatory processes. PMID- 22082078 TI - Experimental evidence for a phylogenetic Janzen-Connell effect in a subtropical forest. AB - Observational evidence increasingly suggests that the Janzen-Connell effect extends beyond the species boundary. However, this has not been confirmed experimentally. Herein, we present both observational and experimental evidence for a phylogenetic Janzen-Connell effect. In a subtropical forest in Guangdong province, China, we observed that co-occurring tree species are less phylogenetically related than expected. The inhibition effects of neighbouring trees on seedling survival decreased with increasing phylogenetic distance between them. In a shade-house experiment, we studied seedling survival of eight species on soil collected close to Castanopsis fissa relative to their survival on soil close to their own adult trees, and found that this relative survival rate increased with phylogenetic distance from C. fissa. This phylogenetic signal disappeared when seedlings were planted in fungicide-treated soil. Our results clearly support negative effects of phylogenetically similar neighbouring trees on seedling survival and suggest that these effects are caused by associated host specific fungal pathogens. PMID- 22082079 TI - A model-based approach to long-term recovery of limb apraxia after stroke. AB - Limb apraxia is a disorder affecting performance of gestures on verbal command (pantomime), on imitation, and/or in tool and action recognition. We aimed to examine recovery on tasks assessing both conceptual and production aspects of limb praxis in left (n = 22) and right (n = 15) stroke patients. Patients were assessed longitudinally on four conceptual tasks (action identification, tool naming by action, tool identification, and tool naming) and five production tasks (pantomime, pantomime by picture, concurrent imitation, delayed imitation, and tool use). They were grouped as impaired or not relative to the performance of a control sample (n = 27) and as acute-subacute (first assessment within 3 months post stroke) or chronic (over 3 months post stroke). Hierarchical linear modeling was used to analyze the data. Acute-subacute and chronic patients had similar average performance. All tasks, except action identification, showed evidence of recovery in both acute and chronic impaired patients. A faster rate of recovery among acute-subacute patients was observed only in the two pantomime tasks (action identification and tool identification were not compared on this factor). PMID- 22082080 TI - Glucose regulation is associated with attentional control performances in nondiabetic older adults. AB - Less efficient glucose regulation, the ability to metabolize glucose, has been associated with poorer cognitive performances in older individuals not meeting criteria for type 2 diabetes ( Messier, Tsiakas, Gagnon, & Desrochers, 2010 ). Yet, the influence of glucose regulation on attentional functions, which are sensitive to aging, is still unclear. The present study examined the relationship between glucose regulation and performances on attentional tasks in nondiabetic older adults. Twenty-two participants (60 years and older) were tested on neuropsychological tests of attention (Trail Making test, modified Stroop test) and on a computerized dual task, after receiving a 50-g glucose drink. Participants with the worse glucose regulation committed more errors on the switching condition of the modified Stroop test (p < .05) and tended to make more errors in divided-attention trials of the computerized dual task (p = .05). Altogether, these results suggest that glucose regulation may transiently influence performances of metabolically healthy older adults on tasks requiring switching attention. PMID- 22082081 TI - Italian norms for the Freedman version of the Clock Drawing Test. AB - BACKGROUND: The Clock Drawing Test (CDT) is a valid screening tool for the evaluation of cognitive decline. This study aimed to compute standardized norms for the Freedman version of the CDT in a population of 248 healthy Italian individuals aged from 20 to 89 years. METHOD: The effects of age, education, and gender on performance were assessed. Three conditions were administered: free drawn clock (FD), which required participants to draw the contour, numbers, hands, and center of the clock; predrawn clock (PD), in which numbers, hands, and center had to be included in a predrawn contour; examiner-drawn clock (ED), in which only hands and center had to be inserted in a template including a predrawn contour and numbers. Scores for each of the single conditions and a total score were calculated. RESULTS: Age had no effect on the FD condition, whereas a significant effect of age was found for the PD and ED conditions and the total score. Gender and education had no influence on any of the scores. Correction grids, cutoffs, and equivalent scores were computed. CONCLUSION: Standardized norms for the Freedman version of the CDT were collected in a large sample of healthy individuals. No adjustments were required for scores on the free-drawn condition, whereas raw scores on the predrawn and examiner-drawn conditions and the total score needed adjustments to account for age effects. The availability of standardized norms for this version of the CDT could increase the use of this comprehensive tool in the detection of dementia. PMID- 22082082 TI - Montreal Cognitive Assessment (MoCA): normative study for the Portuguese population. AB - The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening instrument with good psychometric features and an excellent sensitivity in the early detection of mild cognitive decline. The MoCA was applied to a community based sample of cognitively healthy adults (n = 650), stratified according to sociodemographic variables (age, gender, educational level, geographic region, geographic localization, and residence area), with a distribution similar to that observed in the Portuguese population. The normative data were determined according to age and education as these were the sociodemographic variables that most significantly contributed to the prediction of the MoCA scores, explaining 49% of their variance. PMID- 22082083 TI - Effects of immunosuppressive drugs on the cognitive functioning of renal transplant recipients: a pilot study. AB - Some renal transplant patients show cognitive, emotional, and behavioral changes as part of possible neurotoxic effects associated with immunosuppressive medication, especially tacrolimus. This study evaluated effects of immunosuppressive drugs on some cognitive tasks. Patients treated with sirolimus and cyclosporine reported some of the noncognitive side effects related to immunosuppressive treatment. We observed attention and working memory impairment in patients treated with sirolimus or tacrolimus. Performance of cyclosporine treated subjects was similar to that of healthy volunteer controls. Since the mood, anxiety, and sleep patterns measured were unaffected, it could be concluded that the cognitive deficit found was partly related to treatment. PMID- 22082084 TI - Executive functions, categorization of probabilities, and learning from feedback: what does really matter for decision making under explicit risk conditions? AB - In two experiments with healthy subjects, we used the Game of Dice Task (GDT), the Probability-Associated Gambling (PAG) task, the Iowa Gambling Task (IGT), and executive-function and logical thinking tasks to shed light on the underlying processes of decision making under risk. Results indicate that handling probabilities, as in the PAG task, is an important ingredient of GDT performance. Executive functions and logical thinking also play major roles in deciding in the GDT. Implicit feedback learning, as measured by the IGT, has little impact. Results suggest that good probability handling may compensate for the effects of weak executive functions in decisions under risk. PMID- 22082085 TI - Plasmacytoma of the skull. PMID- 22082087 TI - Coordination and organometallic chemistry of relevance to the rhodium-based catalyst for ethylene hydroamination. AB - The RhCl(3).3H(2)O/PPh(3)/nBu(4)PI catalytic system for the hydroamination of ethylene by aniline is shown to be thermally stable by a recycle experiment and by a kinetic profile study. The hypothesis of the reduction under catalytic conditions to a Rh(I) species is supported by the observation of a high catalytic activity for complex [RhI(PPh(3))(2)](2). New solution equilibrium studies on [RhX(PPh(3))(2)](2) (X = Cl, I) in the presence of ligands of relevance to the catalytic reaction (PPh(3), C(2)H(4), PhNH(2), X(-), and the model Et(2)NH amine) are reported. Complex [RhCl(PPh(3))(2)](2) shows broadening of the (31)P NMR signal upon addition of PhNH(2), indicating rapid equilibrium with a less thermodynamically stable adduct. The reaction with Et(2)NH gives extensive conversion into cis-RhCl(PPh(3))(2)(NHEt(2)), which is however in equilibrium with the starting material and free Et(2)NH. Excess NHEt(2) yields a H-bonded adduct cis-RhCl(PPh(3))(2)(Et(2)NH)...NHEt(2), in equilibrium with the precursors, as shown by IR spectroscopy. The iodide analogue [RhI(PPh(3))(2)](2) shows less pronounced reactions (no change with PhNH(2), less extensive addition of Et(2)NH with formation of cis-RhI(PPh(3))(2)(NHEt(2)), less extensive reaction of the latter with additional Et(2)NH to yield cis RhI(PPh(3))(2)(Et(2)NH)...NHEt(2). The two [RhX(PPh(3))(2)](2) compounds do not show any evidence for addition of the corresponding X(-) to yield a putative [RhX(2)(PPh(3))(2)](-) adduct. The product of C(2)H(4) addition to [RhI(PPh(3))(2)](2), trans-RhI(PPh(3))(2)(C(2)H(4)), has been characterized in solution. Treatment of the RhCl(3).3H(2)O/PPh(3)/nBu(4)PI/PhNH(2) mixture under catalytic conditions yields mostly [RhCl(PPh(3))(2)](2), and no significant halide exchange, demonstrating that the promoting effect of iodide must take place at the level of high energy catalytic intermediates. The equilibria have also been investigated at the computational level by DFT with treatment at the full QM level including solvation effects. The calculations confirm that the bridge splitting reaction is slightly less favorable for the iodido derivative. Overall, the study confirms the active role of rhodium(I) species in ethylene hydroamination catalyzed by RhCl(3).3H(2)O/PPh(3)/nBu(4)PI and suggest that the catalyst resting state is [RhCl(PPh(3))(2)](2) or its C(2)H(4) adduct, RhCl(PPh(3))(2)(C(2)H(4)), under high ethylene pressure. PMID- 22082086 TI - The novel allele HLA-B*35:167 differs from HLA-B*35:03:01 by the amino acid exchange Val152Glu. AB - HLA-B*35:167 allele differs from HLA-B*35:03:01 and HLA-B*35:70 by an amino acid exchange at position 152. PMID- 22082088 TI - Slice orientation and muscarinic acetylcholine receptor activation determine the involvement of N-methyl D-aspartate receptor subunit GluN2B in hippocampal area CA1 long-term depression. AB - BACKGROUND: The contribution of different GluN2 subunits of the N-methyl D aspartate (NMDA) receptor to the induction of bidirectional hippocampal synaptic plasticity is a controversial topic. As both supporting and refuting evidence for the hypothesis of subunit specialization in opposing directions of plasticity has accumulated since it was first proposed a few years ago, we hypothesize that differences in experimental conditions may have in part contributed to some of the inconsistent results from these studies. Here we investigate the controversial hypothesis that long-term depression (LTD) is preferentially induced by GluN2B-containing NMDA receptors in area CA1 of hippocampal slices. RESULTS: We find that brain slices from 2-3 week old rats prepared in the sagittal orientation have GluN2B-independent LTD whereas slices prepared in the coronal orientation have GluN2B-dependent LTD. There was no difference between the orientations in the fraction of the NMDAR EPSC sensitive to a GluN2B selective antagonist, leading us to believe that the intracellular signaling properties of the NMDARs were different in the two preparations. Coronal slices had greater association of LTD-related intracellular signaling protein RasGRF1 with GluN2B relative to sagittal slices. Antagonism of muscarinic acetylcholine receptors (mAChRs) in the sagittal slices returned LTD to a GluN2B-dependent form and increased the association of GluN2B with RasGRF1. CONCLUSIONS: These results suggest a novel form of NMDAR modulation by mAChRs and clarify some disagreement in the literature. PMID- 22082090 TI - Ultrafast transient optical studies of charge pair generation and recombination in poly-3-hexylthiophene(P3ht):[6,6]phenyl C61 butyric methyl acid ester (PCBM) blend films. AB - Charge generation and recombination are studied in blend films of poly-3 hexylthiophene (P3HT) and [6,6']phenyl C61 butyric acid methyl ester (PCBM) using ultrafast transient absorption spectroscopy. We find that the charge generation yield depends upon both blend film composition and thermal annealing. The data suggest that recombination occurs over a wide range of time scales and that, in the least favorable cases, the fastest charge recombination occurs on a time scale similar to exciton diffusion. The results are explained using a simple model that incorporates the effect of P3HT domain size on exciton diffusion and uses empirical models of recombination kinetics. We propose our method as a route to interpretation of spectroscopic data where different processes occur on similar time scales. PMID- 22082089 TI - Double-blind placebo-controlled evaluation of the PROMETATM protocol for methamphetamine dependence. AB - AIMS: To evaluate the efficacy and safety of the PROMETATM Protocol for treating methamphetamine dependence. DESIGN: A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only). SETTING: Three substance abuse treatment clinics: two in patient, one out-patient. PARTICIPANTS: Treatment-seeking, methamphetamine dependent adults (n = 120). MEASUREMENTS: Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial. FINDINGS: No statistically significant between-group differences were detected in urine drug test results, craving, treatment retention or adverse events. CONCLUSIONS: The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving. PMID- 22082092 TI - E pluribus plurima: multidimensional indices and clinical phenotypes in COPD. PMID- 22082093 TI - One-step fabrication of biocompatible chitosan-coated ZnS and ZnS:Mn2+ quantum dots via a gamma-radiation route. AB - Biocompatible chitosan-coated ZnS quantum dots [CS-ZnS QDs] and chitosan-coated ZnS:Mn2+ quantum dots [CS-ZnS:Mn2+ QDs] were successfully fabricated via a convenient one-step gamma-radiation route. The as-obtained QDs were around 5 nm in diameter with excellent water-solubility. These QDs emitting strong visible blue or orange light under UV excitation were successfully used as labels for PANC-1 cells. The cell experiments revealed that CS-ZnS and CS-ZnS:Mn2+ QDs showed low cytotoxicity and good biocompatibility, which offered possibilities for further biomedical applications. Moreover, this convenient synthesis strategy could be extended to fabricate other nanoparticles coated with chitosan.PACS: 81.07.Ta; 78.67.Hc; 82.35.Np; 87.85.Rs. PMID- 22082094 TI - Is it time for new initiatives in the blood center and/or the hospital to reduce bacterial risk of platelets? PMID- 22082095 TI - Test-enhanced learning in the classroom: long-term improvements from quizzing. AB - Three experiments examined whether quizzing promotes learning and retention of material from a social studies course with sixth grade students from a suburban middle school. The material used in the experiments was the course material students were to learn and some of the dependent measures were the actual tests on which students received grades. In within-subject designs, students received three low-stakes multiple-choice quizzes in Experiments 1 and 2 and performance on quizzed items was compared to that on items that were presented twice (Experiment 2) or items that were not presented on the initial quizzes (Experiments 1 and 2). We found that students' performance on both chapter exams and semester exams improved following quizzing relative to either not being quizzed or relative to the twice-presented items. In Experiment 3, students were given one multiple-choice quiz in class and encouraged to quiz themselves outside of class using a Web-based system. The assessment in this experiment was a short answer test in which students had to produce answers, but we also used multiple choice tests. Once again, we found that quizzing of material produced a positive effect on chapter and semester exams. These results show the robustness of retrieval practice via testing as a learning mechanism in a classroom setting using the subject matter of the course and (in most cases) the tests on which students received grades as the dependent measures. Our results add to a growing body of evidence that retrieval practice in the classroom can boost academic performance. PMID- 22082096 TI - Antidiarrheal activity of Laurus nobilis L. leaf extract in rats. AB - In Jordan, the leaves of Laurus nobilis (Family Lauraceae) have been used in folk medicine for the treatment of diarrhea, among other ailments. However, the ethnopharmacology of this plant needs to be scientifically validated. The present work was carried out to evaluate the scientific basis of the antidiarrheal effect of the aqueous extract of L. nobilis leaf. L. nobilis leaf extract significantly inhibited castor oil-induced diarrhea (effective concentration producing 50% of the maximum response [EC(50)]=150+/-6.4 mg/kg) and reduced castor oil-induced enteropooling in rats (EC(50)=162+/-5.9 mg/kg). The extract also significantly inhibited intestinal transit of a charcoal meal and exerted a significant dose dependent relaxation (EC(50)=71+/-5.3 mg/mL) on rat ileal smooth muscle. The aqueous extract tested positive for flavonoids, alkaloids, and tannins. These results established the efficacy of L. nobilis leaf aqueous extract as an antidiarrheal agent and are consistent with the popular use of the plant in the treatment of gastrointestinal disorders, particularly diarrhea. PMID- 22082097 TI - The hexane extract of Saussurea lappa and its active principle, dehydrocostus lactone, inhibit prostate cancer cell migration. AB - Saussurea lappa has been used in Chinese traditional medicine for the treatment of abdominal pain, tenesmus, nausea, and cancer; previous studies have shown that S. lappa also induces G(2) growth arrest and apoptosis in gastric cancer cells. In this study, we investigated the effects of hexane extracts of S. lappa (HESLs) on the migration of DU145 and TRAMP-C2 prostate cancer cells. DU145 and TRAMP-C2 cells were cultured in the presence of 0-4 MUg/mL HESL with or without 10 ng/mL epidermal growth factor (EGF). HESL inhibited the basal and EGF-induced migration of prostate cancer cells in a dose-dependent manner, whereas HESL did not influence the viability of these cancer cells under the conditions used in this study. Active fractions of HESL were separated via column chromatography, and the structure of the active principle was determined using (1)H and (13)C nuclear magnetic resonance spectroscopy. The active compound, dehydrocostus lactone (DHCL), in fraction 7 dose-dependently inhibited the basal and EGF-induced migration of prostate cancer cells. HESL and DHCL reduced matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 secretion but increased TIMP-2 levels in both the absence and presence of EGF. Our results demonstrate that the inhibition of MMP-9 secretion and the stimulation of TIMP-2 secretion contribute to reduced migration of DU145 cells treated with HESL and DHCL. These results indicate that HESL containing its active principle, DHCL, has potential as an antimetastatic agent for the treatment of prostate cancer. PMID- 22082098 TI - Anti-inflammatory activity of Pistacia khinjuk in different experimental models: isolation and characterization of its flavonoids and galloylated sugars. AB - The present study aimed at isolating and elucidating the structure of the main components of Pistacia khinjuk L. and exploring its potential anti-inflammatory effect in different experimental models. The extract was evaluated for anti inflammatory activity by measuring paw volume in three experimental models. Then, prostaglandin E2 (PGE2) level, ear edema, tissue myeloperoxidase (MPO) activity, histopathology, nitric oxide (NO) level, and tumor necrosis factor-alpha (TNF alpha) level were assessed. Seven phenolic compounds, mainly flavonoids and galloylated compounds, were isolated from the aqueous methanol extract: gallic acid (1), methyl gallate (2), quercetin-3-O-beta-D-4C1-galactopyranoside (hyperin) (3), myricetin-3-O-alpha-L-1C4-rhamnopyranoside (myricitrin) (4), 1,6 digalloyl-beta-D-glucose (5), 1,4-digalloyl-beta-D-glucopyranoside (6), and 2,3 di-O-galloyl-(alpha/beta)-4C1-glucopyranose (nilocitin) (7). The anti inflammatory activity was evidenced by decreased carrageenan-induced rat paw edema and PGE2 elevation. In the croton oil-induced ear edema model, MPO activity was significantly inhibited, and inflammatory histopathological changes were ameliorated. In the rat air pouch model, NO generation and TNF-alpha release were significantly inhibited. The isolation and nuclear magnetic resonance spectral data of compound 6 from the genus Pistacia are revealed for the first time. Also, P. khinjuk L. aqueous methanol extract possesses anti-inflammatory activity in several experimental models. PMID- 22082099 TI - Antioxidant and vasodilatory effects of blackberry and grape wines. AB - In contrast to the well-described various biological effects of grape wines, the potential effects of commonly consumed blackberry wine have not been studied. We examined in vitro antioxidant and vasodilatory effects of four blackberry wines and compared them with the effects of two red and two white grape wines. Although some blackberry wines had lower total phenolic content relative to the red grape wines, their antioxidant capacity was stronger, which may be related to a higher content of non-flavonoid compounds (most notably gallic acid) in blackberry wines. Although maximal vasodilation induced by blackberry wines was generally similar to that of red wines, blackberry wines were less potent vasodilators. Vasodilatory activity of all wines, in addition to their flavonoid and total phenolic content, was most significantly associated with their content of anthocyanins. No association of vasodilation with any individual polyphenolic compound was found. Our results indicate the biological potential of blackberry wines, which deserves deeper scientific attention. PMID- 22082100 TI - Anti-Candida activity of Mentha arvensis and Turnera ulmifolia. AB - Candidiasis is the most frequent infection by opportunistic fungi, frequently caused by Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida krusei. Mentha arvensis L. is a herbaceous plant that occurs throughout South America and is used as a tea and in the folk medicine. Turnera ulmifolia L. is already known to be of medicinal value. Ethanol extracts from M. arvensis and T. ulmifolia were assayed for antifungal activity against strains of C. albicans, C. tropicalis, and C. krusei. No clinically relevant antifungal activity was demonstrated by the extracts; however, a potentiation effect was observed when the extracts were applied with metronidazole against C. tropicalis. M. arvensis and T. ulmifolia could represent a source of natural products with modifying antifungal activity. PMID- 22082101 TI - Effect of the edible mushroom Mycoleptodonoides aitchisonii on transient global ischemia-induced monoamine metabolism changes in rat cerebral cortex. AB - We performed a transient bilateral common carotid artery occlusion on rats and investigated whether feeding an aqueous extract of Mycoleptodonoides aitchisonii, an edible mushroom, affected metabolism of monoamines in the cerebral cortex, possibly protecting against ischemic damage. Seventeen days after the surgery, concentrations of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and of homovanillic acid (HVA) in the cerebral cortex of the M. aitchisonii-fed group (MV) were higher than in the control ischemia (CV) group. The turnover rate of DA, which was indicated by (DOPAC+HVA)/DA, for the CV group was significantly lower than for the MV group, and the MV group value was the same rate as the sham-operated group. These data indicate that M. aitchisonii affects the dopaminergic neuronal system following brain ischemia damage in the cerebral cortex. PMID- 22082102 TI - The bioactive potential of red raspberry (Rubus idaeus L.) leaves in exhibiting cytotoxic and cytoprotective activity on human laryngeal carcinoma and colon adenocarcinoma. AB - In this article, the bioactive potential of red raspberry leaves, a by-product of this widely spread plant, mostly valued for its antioxidant-rich fruits, was determined. The polyphenolic profile and antioxidative properties of red raspberry leaf extract were determined and examined for potential biological activity. Cytotoxic effect, antioxidative/prooxidative effect, and effect on total glutathione concentration were determined in human laryngeal carcinoma (HEp2) and colon adenocarcinoma (SW 480) cell lines. SW 480 cells are more susceptible to raspberry leaf extract in comparison with HEp2 cells. The antioxidative nature of raspberry leaf extract was detected in HEp2 cells treated with hydrogen peroxide, as opposed to SW 480 cells, where raspberry leaf extract induced reactive oxygen species formation. Raspberry leaf extract increased total glutathione level in HEp2 cells. This effect was reinforced after 24 hours of recovery, indicating that induction was caused by products formed during cellular metabolism of compounds present in the extract. Comparison of the results obtained on these two cell lines indicates that cellular response to raspberry extract will depend on the type of the cells that are exposed to it. The results obtained confirmed the biological activity of red raspberry leaf polyphenols and showed that this traditional plant can supplement the daily intake of valuable natural antioxidants, which exhibit beneficial health effects. PMID- 22082103 TI - Repeated cerebral ischemia caused by extracranial carotid artery dolichoectasia. AB - We report the case of a 67-year-old man with repeating cerebral embolism caused by a dolichoectatic right common carotid artery. The patient had a history of hypertension, hypercholesterolemia, cigarette smoking, and a postoperative abdominal aortic aneurysm. He presented with a sudden onset of weakness of the left arm and leg. Magnetic resonance imaging revealed old and fresh infarction in the right cerebral hemisphere. Carotid duplex ultrasonography showed a dolichoectatic right common carotid artery with a maximum diameter of 39 mm with thick plaque and strong spontaneous echo contrast. The flow velocity was considerably reduced, which caused thrombus formation, and strong antithrombotic therapy was required. This case provides a rare example of ischemic stroke caused by extracranial carotid artery dolichoectasia. PMID- 22082104 TI - Synchronized release of Doxil and Nutlin-3 by remote degradation of polysaccharide matrices and its possible use in the local treatment of colorectal cancer. AB - A novel approach to the prevention of colorectal cancer (CRC) recurrence by the local, luminal application of the combined therapies: Nutlin-3 (NUT) and the liposomal preparation of doxorubicin, Doxil(*) (Doxil) is presented here. The two drug entities were loaded into calcium alginate beads, engineered to erode upon exposure to a de-crosslinking agent, to allow for the controlled, concomitant release of the two. The synchronized release-driven improved cytotoxicity of NUT and Doxil was tested in vitro in RKO (wild-type p53) and HT-29 (mutant p53) CRC cells, by measuring intracellular expression of p53, p21 and Mdm2, as well as monitoring cell proliferation and viable cell numbers. NUT treatment alone was identified to be cytotoxic exclusively towards RKO cells. However, coadministration of NUT enhanced Doxil's anti-proliferative effects and cell death induction in a synergistic manner in both cell types. It was also identified that combinatorial treatment in a wt p53 context affected the p53 pathway by elevating the expression of p53 and its target p21. The capability of the formulation to erode in the presence of a de-crosslinking agent was demonstrated in vivo in the cecum of the anesthetized rat using indomethacin as a poorly water-soluble PK probe. PMID- 22082105 TI - Biological evaluation of RGDfK-gold nanorod conjugates for prostate cancer treatment. AB - Selective delivery of gold nanorods (GNRs) to sites of prostate tumor angiogenesis is potentially advantageous for localized photothermal therapy. Here, we report the cellular uptake and biodistribution of GNRs surface functionalized with the cyclic RGDfK peptide. The GNRs were synthesized to have a surface plasmon resonance (SPR) peak at 800?nm and grafted with a thiolated poly(ethylene glycol) (PEG) corona with or without RGDfK. The binding and uptake of the targeted (RGDfK) and untargeted GNRs were evaluated in DU145 prostate cancer and human umbilical vein endothelial cells (HUVEC) by high-resolution dark field microscopy, inductively coupled plasma mass spectrometry (ICP-MS), and transmission electron microscopy (TEM). The biodistribution of both GNRs was then evaluated in prostate tumor bearing mice. Targeting of the RGDfK surface-modified GNRs was confirmed in vitro due to selective binding and uptake by endothelial cells. Tumor targeting was not observed in vivo, however, due to fast clearance of the RGDfK-GNRs from the blood. Further modifications of the nanoparticle?s surface properties are needed to enhance localization of the targetable system in sites of tumor angiogenesis. PMID- 22082106 TI - The diffusion of telehealth in rural American Indian communities: a retrospective survey of key stakeholders. AB - OBJECTIVE: Mental health issues are a serious concern for many American Indian Veterans, especially for post-traumatic stress disorder and related psychiatric conditions. Yet, acquiring mental health treatment can be a challenge in Native communities where specialized services are largely unavailable. Consequently, telehealth is increasingly being suggested as a way to expand healthcare access on or near reservation lands. In this study, we wanted to understand the factors affecting the diffusion of telehealth clinics that provided mental health care to rural, American Indian Veterans. MATERIALS AND METHODS: We surveyed 39 key personnel and stakeholders who were involved in the decision-making process, technological infrastructure, and implementation of three clinics. Using Roger Everett's Diffusion Theory as a framework, we gathered information about specific tasks, factors hindering progress, and personal reactions to telehealth both before and after implementation. RESULTS: Many participants expressed initial concerns about using telehealth; however, most became positive over time. Factors that influenced participants' viewpoint largely included patient and staff feedback and witnessing the fulfillment of a community health need. The use of outside information to support the implementation of the clinics and personal champions also showed considerable influence in the clinics' success. CONCLUSION: The findings presented here address critical gaps in our understanding of telehealth diffusion and inform research strategies regarding the cultural issues and outcomes related to telemental health services. Information contained in this report serves as a long overdue guide for developing telemental health programs and policies among American Indians, specifically, and rural populations in general. PMID- 22082107 TI - Barriers to telemedicine: survey of current users in acute care units. AB - CONTEXT: The present study of current telemedicine users is a unique attempt to understand the barriers and motivational factors related to the utilization of telemedicine. OBJECTIVE: A survey of emergency and critical care remote presence telemedicine users was conducted to determine the factors that motivate and the barriers that impede the acceptance and maintenance of a robotic telemedicine (RTM) program. SETTING: The majority of the survey users were in the Emergency Department or in the Intensive Care Unit. METHODS: E-mail invitations were sent to 483 individuals representing 63 healthcare institutions and groups in North America and Europe. Respondents were directed to a Web-based survey. The survey consisted of 96 separate questions, addressing user familiarity and 5-point Likert scales, addressing issues spanning the conceptual and practical issues surrounding adoption of telemedicine. RESULTS: A total of 106 surveys were completed, representing an individual response rate of 21.9% but an institutional response rate of 60.3%. More than two-thirds of the respondents were physicians who participated in active RTM programs. Across seven different topics related to barriers to implementing RTM, the majority of all respondents indicated that cultural issues did not constitute meaningful hurdles, technological matters were generally favorable, and that most personnel were agreeable to both achieving the buy-in to start an RTM program and to maintaining RTM once started. However, respondents proclaimed that RTM's success was still hampered by licensing, credentialing, and malpractice protection, as well as costs, billing, and reimbursement issues. Achieving immediate patient access, overcoming service gaps, improving quality, providing clinical support, maintaining patient satisfaction, and adhering to practice guidelines were viewed as significant motives for RTM implementation. CONCLUSIONS: The leading applications of RTM included emergency response and consultation. The patients, physicians, nurses, nor hospital executives served as barriers to implementation. However, licensing, costs for technology, and reimbursement for RTM continue to impede progress. PMID- 22082108 TI - Using a modified technology acceptance model to evaluate healthcare professionals' adoption of a new telemonitoring system. AB - OBJECTIVE: To examine the factors that could influence the decision of healthcare professionals to use a telemonitoring system. MATERIALS AND METHODS: A questionnaire, based on the Technology Acceptance Model (TAM), was developed. A panel of experts in technology assessment evaluated the face and content validity of the instrument. Two hundred and thirty-four questionnaires were distributed among nurses and doctors of the cardiology, pulmonology, and internal medicine departments of a tertiary hospital. Cronbach alpha was calculated to measure the internal consistency of the questionnaire items. Construct validity was evaluated using interitem correlation analysis. Logistic regression analysis was performed to test the theoretical model. Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were computed. RESULTS: A response rate of 39.7% was achieved. With the exception of one theoretical construct (Habit) that corresponds to behaviors that become automatized, Cronbach alpha values were acceptably high for the remaining constructs. Theoretical variables were well correlated with each other and with the dependent variable. The original TAM was good at predicting telemonitoring usage intention, Perceived Usefulness being the only significant predictor (OR: 5.28, 95% CI: 2.12-13.11). The model was still significant and more powerful when the other theoretical variables were added. However, the only significant predictor in the modified model was Facilitators (OR: 4.96, 95% CI: 1.59-15.55). CONCLUSION: The TAM is a good predictive model of healthcare professionals' intention to use telemonitoring. However, the perception of facilitators is the most important variable to consider for increasing doctors' and nurses' intention to use the new technology. PMID- 22082109 TI - Rapid successions affect microbial N-acetyl-glucosamine uptake patterns during a lacustrine spring phytoplankton bloom. AB - The vernal successions of phytoplankton, heterotrophic nanoflagellates (HNF) and viruses in temperate lakes result in alternating dominance of top-down and bottom up factors on the bacterial community. This may lead to asynchronous blooms of bacteria with different life strategies and affect the channelling of particular components of the dissolved organic matter (DOM) through microbial food webs. We followed the dynamics of several bacterial populations and of other components of the microbial food web throughout the spring phytoplankton bloom period in a pre alpine lake, and we assessed bacterial uptake patterns of two constituents of the labile DOM pool (N-acetyl-glucosamine [NAG] and leucine). There was a clear genotypic shift within the bacterial assemblage, from fast growing Cytophaga Flavobacteria (CF) affiliated with Fluviicola and from Betaproteobacteria (BET) of the Limnohabitans cluster to more grazing resistant AcI Actinobacteria (ACT) and to filamentous morphotypes. This was paralleled by successive blooms of viruses and HNF. We also noted the transient rise of other CF (related to Cyclobacteriaceae and Sphingobacteriaceae) that are not detected by fluorescence in situ hybridization with the general CF probe. Both, the average uptake rates of leucine and the fractions of leucine incorporating bacteria were approximately five to sixfold higher than of NAG. However, the composition of the NAG-active community was much more prone to genotypic successions, in particular of bacteria with different life strategies: While 'opportunistically' growing BET and CF dominated NAG uptake in the initial period ruled by bottom-up factors, ACT constituted the major fraction of NAG active cells during the subsequent phase of high predation pressure. This indicates that some ACT could profit from a substrate that might in parts have originated from the grazing of protists on their bacterial competitors. PMID- 22082110 TI - Design, synthesis, structure, and dehydrogenation reactivity of a water-soluble o iodoxybenzoic acid derivative bearing a trimethylammonium group. AB - 5-Trimethylammonio-1,3-dioxo-1,3-dihydro-1lambda(5)-benzo[d][1,2]iodoxol-1-ol anion (AIBX 1a), an o-iodoxybenzoic acid (IBX) derivative having the trimethylammonium moiety on its phenyl ring, possesses very good solubility in water and distinct oxidative properties from IBX, which is demonstrated in the oxidation of various beta-keto esters to the corresponding dehydrogenated products using water as cosolvent. The regeneration of AIBX 1a can be easily realized from the reaction mixture due to its good water solubility. PMID- 22082111 TI - Transmembrane extension and oligomerization of the CLIC1 chloride intracellular channel protein upon membrane interaction. AB - Chloride intracellular channel proteins (CLICs) differ from most ion channels as they can exist in both soluble and integral membrane forms. The CLICs are expressed as soluble proteins but can reversibly autoinsert into the membrane to form active ion channels. For CLIC1, the interaction with the lipid bilayer is enhanced under oxidative conditions. At present, little evidence is available characterizing the structure of the putative oligomeric CLIC integral membrane form. Previously, fluorescence resonance energy transfer (FRET) was used to monitor and model the conformational transition within CLIC1 as it interacts with the membrane bilayer. These results revealed a large-scale unfolding between the C- and N-domains of CLIC1 as it interacts with the membrane. In the present study, FRET was used to probe lipid-induced structural changes arising in the vicinity of the putative transmembrane region of CLIC1 (residues 24-46) under oxidative conditions. Intramolecular FRET distances are consistent with the model in which the N-terminal domain inserts into the bilayer as an extended alpha helix. Further, intermolecular FRET was performed between fluorescently labeled CLIC1 monomers within membranes. The intermolecular FRET shows that CLIC1 forms oligomers upon oxidation in the presence of the membranes. Fitting the data to symmetric oligomer models of the CLIC1 transmembrane form indicates that the structure is large and most consistent with a model comprising approximately six to eight subunits. PMID- 22082112 TI - Feeding difficulties in children with cerebral palsy: low-cost caregiver training in Dhaka, Bangladesh. AB - BACKGROUND: The majority of children with cerebral palsy have feeding difficulties, which, if not managed, result in stressful mealtimes, chronic malnutrition, respiratory disease, reduced quality of life for caregiver and child, and early death. In well-resourced countries, high- and low-cost medical interventions, ranging from gastrostomy tube feeding to caregiver training, are available. In resource-poor countries such as Bangladesh, the former is not viable and the latter is both scarce and its effectiveness not properly evaluated. The aim of this study was to evaluate the effectiveness of a low-cost, low-technology intervention to improve the feeding practices of carers of children with moderate-severe cerebral palsy and feeding difficulties in Bangladesh. METHODS: An opportunistic sample of 37 caregivers and their children aged 1-11 years were invited to a six-session training programme following an initial feeding assessment with brief advice. During home visits, pre- and post measures of nutritional status, chest health and feeding-related stress were taken and feeding practices were observed. A control phase was evaluated for 20 of the participant pairs following initial assessment with advice, while awaiting full training. RESULTS: A minimum of four training sessions showed significant improvements in the children's respiratory health (P = 0.005), cooperation during mealtimes (P = 0.003) and overall mood (P < 0.001). Improvements in growth were inconsistent. Dramatic reductions were observed in caregiver stress (P < 0.001). A significant difference in the outcomes following advice only compared with advice plus training was also observed. CONCLUSIONS: In situations of poverty, compliance is restricted by lack of education, finances and time. Nonetheless, carers with minimal formal education, living in conditions of extreme poverty were able to change feeding practices after a short, low-cost training intervention, with highly positive consequences. The availability of affordable food supplementation for this population, however, requires urgent attention. PMID- 22082113 TI - Art and authenticity: the importance of originals in judgments of value. AB - Why are original artworks valued more than identical duplicates? The present studies explore 2 mechanisms underlying the special value of original artwork: the assessment of the art object as a unique creative act (performance) and the degree of physical contact with the original artist (contagion). Across 5 experiments, participants were exposed to hypothetical scenarios in which an original object was duplicated. The type of object varied across experiments (e.g., a painting vs. a piece of furniture) as did the circumstances surrounding the creation of the original object and the duplicate. Overall, the results support assessments of performance and contagion as key factors underlying the value of original artwork, and they are consistent with the conclusion that the discrepancy in value between original artworks and perfect duplicates derives from people's lay theories about the domain of art, rather than from associations with particular kinds of art or certain cases of forgery. PMID- 22082114 TI - Performance costs when emotion tunes inappropriate cognitive abilities: implications for mental resources and behavior. AB - Emotion tunes cognition, such that approach-motivated positive states promote verbal cognition, whereas withdrawal-motivated negative states promote spatial cognition (Gray, 2001). The current research examined whether self-control resources become depleted and influence subsequent behavior when emotion tunes an inappropriate cognitive tendency. In 2 experiments, either an approach-motivated positive state or a withdrawal-motivated negative state was induced, and then participants completed a verbal or a spatial working memory task creating conditions of emotion-cognition alignment (e.g., approach/verbal) or misalignment (e.g., approach/spatial). A control condition was also included. To examine behavioral costs due to depleted self-control resources, participants completed either a Stroop task (Stroop, 1935; Experiment 1) or a Black/White implicit association test (IAT; Greenwald, McGhee, & Schwartz, 1998; Experiment 2). Participants in the misalignment conditions performed worse on the Stroop task, and they were worse at controlling their implicit attitude biases on the IAT. Thus, when emotion tunes inappropriate cognitive tendencies for one's current environment, self-control resources become depleted, impairing behavioral control. PMID- 22082115 TI - The interplay between nonsymbolic number and its continuous visual properties. AB - To date, researchers investigating nonsymbolic number processes devoted little attention to the visual properties of their stimuli. This is unexpected, as nonsymbolic number is defined by its visual characteristics. When number changes, its visual properties change accordingly. In this study, we investigated the influence of different visual properties on nonsymbolic number processes and show that the current assumptions about the relation between number and its visual characteristics are incorrect. Similar to previous studies, we controlled the visual cues: Each visual cue was not predictive of number. Nevertheless, participants showed congruency effects induced by the visual properties of the stimuli. These congruency effects scaled with the number of visual cues manipulated, implicating that people do not extract number from a visual scene independent of its visual cues. Instead, number judgments are based on the integration of information from multiple visual cues. Consequently, current ways to control the visual cues of the number stimuli are insufficient, as they control only a single variable at the time. And, more important, the existence of an approximate number system that can extract number independent of the visual cues appears unlikely. We therefore propose that number judgment is the result of the weighing of several distinct visual cues. PMID- 22082116 TI - Social class differences in N400 indicate differences in spontaneous trait inference. AB - An emerging literature indicates that dispositional bias in causal attribution of social behavior is weaker for people with working-class (vs. middle-class) backgrounds. However, it is unknown whether this difference is also present in spontaneous forms of trait inference. In the current work, American undergraduates were asked to merely memorize many pairings of a target face and a trait-implying behavior. In a subsequent lexical judgment task, after each face was presented as a fixation, either an implied trait or its antonym was given as a target. As expected, participants with college-educated parents (middle class) showed a strong N400 event-related potential component to the antonym (vs. the implied trait), suggesting spontaneous trait inference during the memorization phase. In contrast, those with high-school-educated parents (working class) showed no such effect. It is important to note that the N400 spontaneous trait inference effect was associated with perceived significance of dispositions in accounting for social behaviors. PMID- 22082117 TI - Oral sampling and human papillomavirus genotyping in HIV-infected patients. AB - BACKGROUND: Oral human papillomavirus (HPV) is associated with several health complications especially in combination with HIV infections. Screening may be useful, but methodologies and results have varied widely in previous studies. We conducted a pilot study in an HIV-positive population to evaluate HPV detection in four different oral sample types. METHODS: Upon enrollment, an oral-rinse (OR) sample was collected in 10 ml saline. Additional samples of the buccal mucosa, tonsils, and oral lesion if present were collected with cytology brushes. DNA was extracted using LC-MagNAPure, and the Linear Array HPV genotyping Assay (Roche) was used for HPV genotyping. RESULTS: In samples from 100 HIV-positive participants, HPV was detected in 39 (%) of the oral rinses, 13 (%) mucosal and 11 (12.9%) tonsil brushings. Of seven lesion brushings collected, four were HPV positive. All participants with HPV detected in mucosal, tonsil, or lesion brushings were also positive in the OR sample. Among the rinse samples, 27 different genotypes were detected with HPV84 (n = 6), HPV55 (n = 5), and HPV83 (n = 5) being the most common. Multiple infections were detected in 17 samples (range 2-9, mean 1.9 types). As potential cofactors, only receptive oral sex was significantly associated with HPV (P = 0.018, odds ratio 2.9, 95% CI 1.2-6.9). CONCLUSION: Sampling is a significant factor for oral prevalence studies. Oral rinse provides the best representation for HPV in the oral cavity. To evaluate associated cofactors other than receptive oral sex, larger studies with case control design are necessary. PMID- 22082118 TI - A retrospective study on the efficacy of pubic symphysis corticosteroid injections in the treatment of pubic symphysis pain. AB - OBJECTIVE: To report immediate and follow-up pain intensity outcomes of fluoroscopically guided contrast- enhanced pubic symphysis corticosteroid injections for patients with pubic symphysis pain (PSP). DESIGN: Retrospective medical record review. SETTING: Outpatient rehabilitation clinic. SUBJECTS: Patients with PSP who underwent pubic symphysis corticosteroid injection (PSI). INTERVENTION: Pubic symphysis corticosteroid injection. OUTCOME MEASURES: Pain intensity as measured by numeric rating scale (NRS). RESULTS: Fourteen patients (4 men and 10 women) underwent PSI. Five patients had PSP for less than 6 months, nine had chronic pain (>than 6 months). In 7 of the 10 women the pain was pregnancy related. All patients received other treatments prior to injection. Pubic symphysis tenderness was the most common physical examination finding (13/14 patients). Follow-up pain intensity (PI)-NRS improvement of greater than 2 points was considered clinically significant. At follow-up, improvement was not statistically significant (Wilcoxon signed-rank test, z=1.62 P=0.10). Patients with pain <6 months did not have a greater likelihood of benefit at follow-up compared with those with pain for >6 months (Fisher's exact test, P=0.775). CONCLUSIONS: PSIs do not provide clinically or statistically significant relief at follow-up in patients with PSP. PMID- 22082119 TI - Synthesis and self-assembly of thermoresponsive PEG-b-PNIPAM-b-PCL ABC triblock copolymer through the combination of atom transfer radical polymerization, ring opening polymerization, and click chemistry. AB - A well-defined thermoresponsive poly(ethylene glycol)-block-poly(N isopropylacrylamide)-block-poly(epsilon-caprolactone) (PEG(43)-b-PNIPAM(82)-b PCL(87)) triblock copolymer was synthesized by combination of atom transfer radical polymerization (ATRP), ring-opening polymerization (ROP), and click chemistry. The synthesis included the four steps, and all the structures of the polymers were determined. The thermoresponsive triblock copolymer can disperse in water at room temperature to form core-shell-corona micelles with the hydrophobic PCL block as core, the thermoresponsive PNIPAM block as shell, and the hydrophilic PEG block as corona. At temperatures above the lower critical solution temperature (LCST) of the PNIPAM block, the PNIPAM chains gradually collapse on the PCL core to shrink the size and change the structure of the resultant core-shell-corona micelles with temperature increasing. PMID- 22082120 TI - The desperate need for good-quality clinical trials to evaluate the optimal source and dose of fibrinogen in managing bleeding. AB - Recent interest in transfusion management of trauma patients has heightened expectation in the role of blood component therapy in improving patient outcome. Optimal transfusion support in supplementation with fibrinogen has not been defined by high-quality evidence. Current evidence comes mainly from case series and uncontrolled studies and does not support the superiority of one source of fibrinogen over another or the optimal schedule or dose for patient benefit. There are unanswered questions about safety, especially the effects on the risk of hospital-acquired venous thromboembolism, an important consideration in any therapy that alters the hemostatic balance. Studies of cost-effectiveness have not been considered in research. An international move to supplement fibrinogen more 'aggressively' without direct clinical evaluation beforehand represents a failed opportunity to improve our very limited understanding of optimal transfusion practice. PMID- 22082121 TI - Screening of the pelvic organ prolapse without a physical examination; (a community based study). AB - BACKGROUND: Pelvic organ prolapse (POP) is a silent disorder with a huge impact on women's quality of life. There is limited data from community-based studies conducted to determine the prevalence of POP as its assessment needs a pelvic examination. We aimed to develop a simple screening inventory for identification of pelvic organ prolapse and then evaluate its sensitivity and specificity. METHODS: This study had two phases. In the first phase in order to develop a simple inventory for assessment of POP, the Pelvic Floor Disorder Inventory (PFDI) was completed for a convenience sample of 200 women, aged 18-45 years, referred for annual gynecologic examination, and their pelvic organ prolapse was assessed using the standard protocol. The most sensitive and specific questions were selected as pelvic organ prolapse simple screening inventory (POPSSI). In the second phase, using a stratified multistage probability cluster sampling method, the sensitivity and specificity of the POPSSI was investigated in a non selected sample of 954 women recruited from among reproductive aged women living in four randomly selected provinces of Iran. RESULTS: The sensitivity and specificity of POPSSI for identification of pelvic organ prolapse in the general population were 45.5 and 87.4% respectively; these values were 96.7 and 20% among those women who were aware of their pelvic dysfunction. CONCLUSION: Community based screening studies on pelvic organ prolapse could be facilitated by using the POPSSI, the sensitivity of which would be enhanced through conducting of public awareness programs. PMID- 22082122 TI - Dronedarone in atrial fibrillation--Jekyll and Hyde? PMID- 22082123 TI - Characterization of four novel HLA alleles, including two in the same haplotype. AB - Characterization of the novel HLA alleles A*02:330, A*11:108, B*40:175, and B*40:176 is described. PMID- 22082124 TI - Comparison of nanofiltration efficacy in reducing infectivity of centrifuged versus ultracentrifuged 263K scrapie-infected brain homogenates in "spiked" albumin solutions. AB - BACKGROUND: The safety of plasma-derived products is of concern for possible transmission of variant Creutzfeldt-Jakob disease. The absence of validated screening tests requires the use of procedures to remove or inactivate prions during the manufacture of plasma-derived products to minimize the risk of transmission. These procedures need proper validation studies based on spiking human plasma or intermediate fractions of plasma fractionation with prions in a form as close as possible to that present in blood. STUDY DESIGN AND METHODS: Human albumin was spiked with low-speed or high-speed supernatants of 263K scrapie-infected hamster brain homogenates. Spiked albumin was then passed through a cascade of filters from 100 nm down to 20 to 15 nm. Residual infectivity was measured by bioassay. RESULTS: The overall removal of infectivity spiked into albumin through serial nanofiltration steps was 4 to 5 logs using low speed supernatant and 2 to 3 logs with high-speed supernatant. CONCLUSION: These findings confirm the utility of nanofiltration in removing infectivity from plasma (or other products) spiked with scrapie brain homogenate supernatants. However, efficiency is diminished using supernatants that have been ultracentrifuged to reduce aggregated forms of the infectious agent. Thus, filtration removal data based on experiments using "standard" low-speed centrifugation supernatants might overestimate the amount of prion removal in plasma or urine-derived therapeutic products. PMID- 22082125 TI - Four neonates with giant ovarian cysts: difficulties in diagnosis and decision making process. AB - OBJECTIVE: Ovarian cysts compose most of the intraabdominal cysts in fetal period. Most of them regress spontaneously at intrauterine or postnatal period. The cysts that are complicated and do not regress are excised generally. METHODS: Here we report a case series that consists of four newborns having giant (>= 10 cm) ovarian cysts. All of the patients were term infants and followed for ovarian cysts in intrauterine period. RESULTS: Patients were operated on 5, 11, 28, 47th days, respectively. Three patients had unilateral cysts (two right, one left) and one had bilateral cysts. One of the four patients had bilateral ovarian cysts, 100 * 95 mm in diameter on the left and 50 * 55 mm on the right, which was torsioned. CONCLUSION: The risk of complications is higher in bilateral cysts even they are smaller, and early surgical intervention should be done to these patients. During the operation of one of the patients, we detected the cyst at the opposite side that was shown by ultrasonography. Since the size of the mass is large, detecting the correct origin of the cyst is important for the selection of appropriate surgical approach. PMID- 22082126 TI - Correlated mutations via regularized multinomial regression. AB - BACKGROUND: In addition to sequence conservation, protein multiple sequence alignments contain evolutionary signal in the form of correlated variation among amino acid positions. This signal indicates positions in the sequence that influence each other, and can be applied for the prediction of intra- or intermolecular contacts. Although various approaches exist for the detection of such correlated mutations, in general these methods utilize only pairwise correlations. Hence, they tend to conflate direct and indirect dependencies. RESULTS: We propose RMRCM, a method for Regularized Multinomial Regression in order to obtain Correlated Mutations from protein multiple sequence alignments. Importantly, our method is not restricted to pairwise (column-column) comparisons only, but takes into account the network nature of relationships between protein residues in order to predict residue-residue contacts. The use of regularization ensures that the number of predicted links between columns in the multiple sequence alignment remains limited, preventing overprediction. Using simulated datasets we analyzed the performance of our approach in predicting residue residue contacts, and studied how it is influenced by various types of noise. For various biological datasets, validation with protein structure data indicates a good performance of the proposed algorithm for the prediction of residue-residue contacts, in comparison to previous results. RMRCM can also be applied to predict interactions (in addition to only predicting interaction sites or contact sites), as demonstrated by predicting PDZ-peptide interactions. CONCLUSIONS: A novel method is presented, which uses regularized multinomial regression in order to obtain correlated mutations from protein multiple sequence alignments. AVAILABILITY: R-code of our implementation is available via http://www.ab.wur.nl/rmrcm. PMID- 22082127 TI - Th17-related cytokines: new players in the control of chronic intestinal inflammation. AB - Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD) in man, are thought to be caused by an excessive and poorly controlled immune response that is directed against components of the normal microflora. The exact sequence of events by which this pathological process is triggered and maintained is not fully understood, but studies in experimental models of IBD and data emerging from recent clinical trials indicate that T cell derived cytokines are crucial mediators of the tissue damage. Although CD and UC have been traditionally considered two typical examples of T helper (Th)1 or Th2 associated disease respectively, it is now known that CD- and UC-related inflammation is also marked by enhanced production of cytokines made by a distinct subset of Th cells, termed Th17 cells. Th17 cytokines can have both tissue-protective and inflammatory effects in the gut and there is evidence that Th17 cells can alter their cytokine program according to the stimuli received and convert into Th1-producing cells. These novel findings have contributed to advancing our understanding of mechanisms of gut tissue damage and open new avenues for development of therapeutic strategies in IBD. PMID- 22082128 TI - Mineralocorticoid receptor antagonists for heart failure. AB - INTRODUCTION: Although mineralocorticoid receptor (MR) antagonists are indicated in systolic heart failure, they are underprescribed in patients with appropriate indications for their prescription and often used in those in whom the evidence for probable benefit is scant. The rate of adverse events in practice has exceeded that foreshadowed by randomized controlled trials (RCTs). With the recent publication of the landmark therapeutic trial (EMPHASIS), it is timely to review the appropriate use of these agents in heart failure. AREAS COVERED: This review addresses the pathophysiological importance of MR activation in heart failure and summarizes pivotal RCTs of MR antagonists in heart failure. EXPERT OPINION: MR antagonism reduces mortality and morbidity in heart failure with reduced systolic function in severe chronic disease, in heart failure complicating myocardial infarction and also in those with impaired systolic function (but only mild symptoms). Evidence for benefits in a significant proportion of 'real-life' patients with heart failure, including those with preserved left ventricular ejection fraction, is lacking. MR antagonism is an important part of the pharmaceutical armamentarium in managing heart failure but must be prescribed with careful case selection, taking note of the evidence of where risks are acceptable and benefits are likely. PMID- 22082129 TI - Intracranial angioplasty and stenting through direct carotid puncture. AB - BACKGROUND AND PURPOSE: To describe a case of successful intracranial angioplasty and stenting of a symptomatic middle cerebral artery (MCA) stenosis using a transcervical approach. METHODS: A 73-year-old woman presented with several ischemic strokes in the left MCA distribution. A diagnostic cerebral angiogram demonstrated more than 80% stenosis of her left MCA. Because the patient failed maximal medical therapy, it was decided to perform angioplasty and stenting. Given the patient's tortuous arch and rigid vessels, access was obtained through a transcutaneous puncture with direct visualization of the surgically exposed common carotid artery (CCA). RESULTS: The patient tolerated well the procedure and after successful stenting her symptoms resolved. CONCLUSION: Access of the intracranial circulation through direct CCA puncture may be a feasible alternative when the transfemoral access is not possible. The transcervical approach may be safe even with the use of antiplatelet medications and anticoagulation. PMID- 22082130 TI - Effect of cholesterol on the membrane interaction of Modelin-5 isoforms. AB - Modelin-5 isoforms were used to gain an insight into the effects of amidation on antimicrobial selectivity. When tested against Escherichia coli, amidation increased toxicity 10-fold (MIC = 31.25 MUM) while showing limited increased hemolytic activity (2% lysis). Our results show that both the amidated and non amidated peptides had a disordered structure in aqueous solution (<18% helical) and folded to form helices at the membrane interface (for example, >43% in the presence of DMPC). The stabilization of the helical structure by amidation has previously been shown to play a key role in increasing antibacterial efficacy. The presence of cholesterol in the membrane increases the packing density (C(s)( 1) values 25-33 mN m(-1)) and so prevents the peptide from forming stable association with the membrane, which is evidenced by the higher binding coefficient (K(d)) in the presence of cholesterol: 57.70 MUM for Modelin-5-COOH and 35.64 MUM for Modelin-5-CONH(2) compared to the presence of E. coli lipid extract (10 MUM), which would prevent local concentration of the peptide at the bilayer interface as seen by reduction in monolayer interaction. This in turn would be predicted to inhibit activity. PMID- 22082131 TI - Loss of heterozygosity (LOH) in tumour suppressor genes in benign and malignant mixed odontogenic tumours. AB - Although molecular alterations are reported in different types of odontogenic tumours, their pathogenesis remains to be established. Loss of heterozygosity (LOH) studies allow the identification of minimal regions of deletions of known or putative tumour suppressor genes, the losses of which may promote neoplastic growth. The purpose of this study was to investigate LOH in a set of odontogenic mixed tumours. Tumour suppressor gene loci on 3p, 9p, 11p, 11q and 17p chromosomes were analysed in five samples of ameloblastic fibroma (AF), three samples of ameloblastic fibro-odontoma (AFO) and three samples of ameloblastic fibrosarcoma (AFS). The most frequently lost genetic loci were p53 (17p13, 62%) and CHRNB1 (17p13, 55%). LOH at the chromosome regions 3p24.3, 9p22 and 9p22-p21 was identified only in AFS. No sample showed LOH at the chromosomal loci 3p21.2 and 11q13.4. For the region 9p22-p13, LOH occurred in one sample of AFO. The fractional allelic loss (FAL) was calculated for each sample. The mean FAL of the benign lesions (i.e. AF and AFO) was 22%, whereas the mean FAL of the malignant lesions (i.e. AFS) was 74.6%. In conclusion, our results show a higher FAL in AFS compared to its benign counterparts and reveal a different pattern of LOH of tumour suppressor genes in AFS, which may regulate changes in tumour behaviour. PMID- 22082132 TI - "I am nothing": experiences of loss among women suffering from severe birth injuries in Tanzania. AB - BACKGROUND: Despite the increased attention on maternal mortality during recent decades, which has resulted in maternal health being defined as a Millennium Development Goal (MDG), the disability and suffering from obstetric fistula remains a neglected issue in global health. Continuous leaking of urine and the physical, emotional and social suffering associated with it, has a profound impact on women's quality of life. This study seeks to explore the physical, cultural and psychological dimensions of living with obstetric fistula, and demonstrate how these experiences shape the identities of women affected by the condition. METHODS: A cross-sectional study with qualitative and quantitative components was used to explore the experiences of Tanzanian women living with obstetric fistula and those of their husbands. The study was conducted at the Comprehensive Community Based Rehabilitation Tanzania hospital in Dar es Salaam, Bugando Medical Centre in Mwanza, and Mpwapwa district, in Dodoma region. Conveniently selected samples of 16 women were interviewed, and 151 additional women responded to a questionnaire. In addition, 12 women affected by obstetric fistula and six husbands of these affected women participated in a focus group discussions. Data were analysed using content data analysis framework and statistical package for the social sciences (SPSS) version 15 for Microsoft windows. RESULTS: The study revealed a deep sense of loss. Loss of body control, loss of the social roles as women and wives, loss of integration in social life, and loss of dignity and self-worth were located at the core of these experiences. CONCLUSION: The women living with obstetric fistula experience a deep sense of loss that had negative impact on their identity and quality of life. Acknowledging affected women's real-life experiences is important in order to understand the occurrence and management of obstetric fistula, as well as prospects after treatment. This knowledge will help to improve women's sense of self-worth and maintain their identity as women, wives, friends and community members. Educational programmes to empower women socially and economically and counselling of families of women living with obstetric fistula may help these women receive medical and social support that is necessary. PMID- 22082133 TI - Association and microheterogeneity in aqueous 2-butoxyethanol solutions. AB - Molecular dynamics simulations are employed to investigate aggregation and microheterogeneity in dilute solutions of 2-butoxyethanol (BE) in water. The BE concentration is varied from near infinite dilution to the mole fraction X(BE) = 0.04. It was found that large systems (32,000 molecules) are necessary to accommodate the BE aggregates that form in this concentration range. Simulations were performed with two different force fields, and similar results were obtained. At very low concentration, BE aggregation is not observed, but evidence is found for intramolecular hydrogen bonds (between the hydroxyl hydrogen and the ether oxygen of the same BE molecule) that form five-member ring configurations, similar to those reported in experimental studies of BE in nonaqueous solvent. Initial signs of BE association appear at X(BE) ~ 0.005, after which aggregation occurs rapidly, with aggregates that can be described as micelle-like being fully formed at X(BE) ~ 0.02. This concentration agrees well with many experimental studies of aggregation in BE-water solutions. Between X(BE) = 0.02 and 0.04, the aggregates appear to grow a little in size, but the basic structure remains the same. At long range, the various pair correlation functions show clear density oscillations associated with BE aggregation. This allows us to identify the length scales of the existing microheterogeneity and to estimate the size of the BE aggregates. If we assume spherical aggregates, then our estimate of the radius at X(BE) = 0.04 (~42 A) is close to estimates obtained from light scattering and small-angle neutron scattering experiments. PMID- 22082135 TI - Sexual, psychological, and relational functioning in women after surgical treatment for vulvar malignancy: a literature review. AB - INTRODUCTION: Vulvectomy is an intrusive treatment option for women with vulvar malignancy that theoretically may affect sexual function. AIM: This study aims to provide a comprehensive review of the literature on the impact of surgical treatment for vulvar malignancy on sexual functioning, overall quality of life, and partner relationship. METHODS: Systematic search of the medical literature on PubMed, PsycINFO, Cochrane database, Google Scholar and Embase using a number of related terms including vulvar malignancy, vulvar cancer, vulva cancer, vulval cancer, vulvectomy, sexual function, partner relation, quality of life, and psychological functioning. MAIN OUTCOME MEASURE: Measures and indicators of sexual function, overall quality of life, and partner relationship following vulvectomy for vulvar malignancy. RESULTS: There is evidence that women who undergo surgical treatment for vulvar cancer or vulvar intraepithelial neoplasia are at high risk for sexual dysfunctions, dissatisfaction with partner relationship, and psychological difficulties. Factors associated with posttreatment sexual dysfunction include patient's increased age, poor overall well-being, history of depression, anxiety, and excision size of vulvar malignancy. CONCLUSIONS: Surgical treatment of vulvar cancer has a negative impact on sexual function, quality of life, and satisfaction with partner relationship. However, hitherto only little research effort has been directed to postoperative sexual well-being in vulvar cancer survivors. There is a need for more methodological sound prospective studies that explore sexual function, quality of life, and partner relationship and its predictors over time in vulvar cancer patients. PMID- 22082134 TI - A meta-analysis of CAG (cytarabine, aclarubicin, G-CSF) regimen for the treatment of 1029 patients with acute myeloid leukemia and myelodysplastic syndrome. AB - The regimen of cytarabine, aclarubicin and G-CSF (CAG) has been widely used in China and Japan for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We searched literature on CAG between 1995 and 2010 and performed a meta-analysis to determine its overall efficacy using a random-effects or fixed effects model. Thirty five trials with a total of 1029 AML (n = 814) and MDS (n = 215) patients were included for analysis. The CR rate of AML (57.9%) was significantly higher than that of MDS (45.7%) (p < 0.01). No difference in CR was noted between the new (56.7%) and relapsed/refractory AML (60.1%) (p > 0.05). The CR rate was also significantly higher in patients with favorable (64.5%) and intermediate (69.6%) karyotypes than those with unfavorable one (29.5%) (p < 0.05). Remarkably, the CR rate of CAG was significantly higher than those of non CAG regimens (odds ratio 2.43). CAG regimen was well tolerated, with cardiotoxicity in 2.3% and early death in 5.2% of the cases. In conclusion, CAG regimen was an effective and safe regimen for the treatment of AML, and may be more effective than non-CAG regimens. Randomized controlled trials are strongly recommended to evaluate its efficacy and safety in comparison with the current standard treatment. PMID- 22082136 TI - Enzymatically catalyzed synthesis of low-calorie structured lipid in a solvent free system: optimization by response surface methodology. AB - A kind of low-calorie structured lipid (LCSL) was obtained by interesterification of tributyrin (TB) and methyl stearate (St-ME), catalyzed by a commercially immobilized 1,3-specific lipase, Lipozyme RM IM from Rhizomucor miehei . The condition optimization of the process was conducted by using response surface methodology (RSM). The optimal conditions for highest conversion of St-ME and lowest content LLL-TAG (SSS and SSP; S, stearic acid; P, palmitic acid) were determined to be a reaction time 6.52 h, a substrate molar ratio (St-ME:TB) of 1.77:1, and an enzyme amount of 10.34% at a reaction temperature of 65 degrees C; under these conditions, the actually measured conversion of St-ME and content of LLL-TAG were 78.47 and 4.89% respectively, in good agreement with predicted values. The target product under optimal conditions after short-range molecular distillation showed solid fat content (SFC) values similar to those of cocoa butter substitutes (CBS), cocoa butter equivalent (CBE), and cocoa butters (CB), indicating its application for inclusion with other fats as cocoa butter substitutes. PMID- 22082137 TI - The use of botulinum toxins for the management of chronic pain and headache: making the most of an evidence-based medicine approach for these rapidly evolving treatments. PMID- 22082138 TI - Maternal effects and heritability of annual productivity. AB - Within-individual consistency and among-individual heterogeneity in fitness are prerequisites for selection to take place. Within-individual variation in productivity between years, however, can vary considerably, especially when organisms become older and more experienced. We examine individual consistency in annual productivity, the covariation between survival and annual productivity, and the sources of variation in annual productivity, while accounting for advancing age, to test the individual-quality and resource-allocation life history theory hypotheses. We use long-term data from a pedigreed, wild population of house sparrows. Within-individual annual productivity first increased and later decreased with age, but there were no selective mortality due to individual quality and no correlation between lifespan and productivity. Individuals were consistent in their annual productivity (C = 0.49). Narrow-sense heritability was low (h(2) = 0.09), but maternal effects explained much of the variation (M = 0.33). Such effects can influence evolutionary processes and are of major importance for our understanding of how variation in fitness can be maintained. PMID- 22082139 TI - Diffusion tensor imaging and tractography of the corticospinal tract in the presence of enlarged Virchow-Robin spaces. AB - BACKGROUND AND PURPOSE: We report a patient with abnormal diffusion tensor imaging (DTI) and tractography of the corticospinal tract caused by mass effect from adjacent enlarged Virchow-Robin spaces. METHODS: DTI was performed using 25 noncollinear directions. Fractional anisotropy (FA) and mean diffusivity (MD) maps were generated. Region-of-interest measurements of the corticospinal tracts were organized in histograms, and comparisons were made between sides. Statistical analysis consisted of a Wilcoxon rank-sum nonparametric test and a two-sample test of proportions to compare the relative percentage of voxels >.8. RESULTS: The patient had no signs or symptoms of motor weakness. The corticospinal tract adjacent to the enlarged Virchow-Robin spaces showed significant changes in the proportion of FA > .8, distribution of FA and distribution of MD (P < .001). CONCLUSIONS: Diffusion tensor changes may be caused by enlarged Virchow-Robin spaces in the absence of clinical signs or symptoms. We hypothesize that the DTI changes are due to alterations in the extravascular extracellular space. Tensor changes should be interpreted with caution in patients with space occupying mass lesions such as brain tumors. PMID- 22082140 TI - On the validity of the likelihood ratio test and consistency of resulting parameter estimates in joint linkage and linkage disequilibrium analysis under improperly specified parametric models. AB - It has been shown that parametric analysis of linkage disequilibrium conditional on linkage using an overly deterministic model can be optimal for family-based association analysis. However, if one applies this strategy carelessly, there is a risk of false inference. We analyse properties of such likelihood ratio tests when the assumed disease mode of inheritance is inaccurate. Under some conditions, problems result if one is not careful to consider what null hypothesis is being tested. We show that: (a) tests for which the null hypothesis assumes the absence of both linkage and association are independent of the true mode of inheritance; (b) likelihood ratio tests assuming either linkage or association under the null hypothesis may depend on the true mode of inheritance, leading to inconsistent parameter estimates, in particular under extremely deterministic models; (c) this problem cannot be eliminated by increasing sample size or adding population controls--as sample size increases, the chance of false positive inference goes to 100%; (d) this issue can lead to systematic false positive inference of association in regions of linkage. This is important because highly deterministic models are often used intentionally in model-based analyses because they can have more power than the true model, and are implicit in many model-free analysis methods. PMID- 22082141 TI - Evaluation of maternal knowledge level about neonatal jaundice. AB - OBJECTIVE: To evaluate the knowledge of mothers on neonatal jaundice. METHODS: This study was conducted on 161 mothers who had given birth to healthy newborns at Izmir Aegean Gynecology and Obstetrics Hospital between January 2010 and April 2010. A questionnaire was used to assess the mothers' knowledge on neonatal jaundice. Knowledge was evaluated as "sufficient" or "insufficient" based on responses. Sufficiently informed mothers were compared with insufficiently informed group for the knowledge level about neonatal jaundice. RESULTS: The rate of insufficiently informed mothers was 53.6%. Logistic regression analysis showed that education level and having a previous offspring with jaundice were independent variables affecting the mothers' knowledge level. Low education level was found to increase the probability of the mothers' knowledge level to be insufficient by 2.1 folds (OR 2.1, 95% CI 1.3-3.4; p = 0.003). Being informed beforehand by a previous offspring with jaundice increased the probability of the mothers' knowledge to be sufficient by twofolds (OR 2, 95% CI 1.1-3.7; p = 0.03). CONCLUSION: It is found that the mothers' knowledge about neonatal jaundice is insufficient. Maternal education level and having a previous offspring with jaundice are major factors affecting the knowledge of the mothers on hyperbilirubinemia. PMID- 22082142 TI - Canalization effect in the coagulation cascade and the interindividual variability of oral anticoagulant response. A simulation study. AB - BACKGROUND: Increasing the predictability and reducing the rate of side effects of oral anticoagulant treatment (OAT) requires further clarification of the cause of about 50% of the interindividual variability of OAT response that is currently unaccounted for. We explore numerically the hypothesis that the effect of the interindividual expression variability of coagulation proteins, which does not usually result in a variability of the coagulation times in untreated subjects, is unmasked by OAT. RESULTS: We developed a stochastic variant of the Hockin-Mann model of the tissue factor coagulation pathway, using literature data for the variability of coagulation protein levels in the blood of normal subjects. We simulated in vitro coagulation and estimated the Prothrombin Time and the INR across a model population. In a model of untreated subjects a "canalization effect" can be observed in that a coefficient of variation of up to 33% of each protein level results in a simulated INR of 1 with a clinically irrelevant dispersion of 0.12. When the mean and the standard deviation of vitamin-K dependent protein levels were reduced by 80%, corresponding to the usual Warfarin treatment intensity, the simulated INR was 2.98 +/- 0.48, a clinically relevant dispersion, corresponding to a reduction of the canalization effect.Then we combined the Hockin-Mann stochastic model with our previously published model of population response to Warfarin, that takes into account the genetical and the phenotypical variability of Warfarin pharmacokinetics and pharmacodynamics. We used the combined model to evaluate the coagulation protein variability effect on the variability of the Warfarin dose required to reach an INR target of 2.5. The dose variance when removing the coagulation protein variability was 30% lower. The dose was mostly related to the pretreatment levels of factors VII, X, and the tissue factor pathway inhibitor (TFPI). CONCLUSIONS: It may be worth exploring in experimental studies whether the pretreatment levels of coagulation proteins, in particular VII, X and TFPI, are predictors of the individual warfarin dose, even though, maybe due to a canalization-type effect, their effect on the INR variance in untreated subjects appears low. PMID- 22082143 TI - Medical management of neurocysticercosis. AB - INTRODUCTION: Neurocysticercosis (NCC) is considered to be the most common cause of acquired epilepsy worldwide. Formerly restricted to palliative measures, therapy for NCC has advanced with the advent of two drugs that are considered to be effective: praziquantel (PZQ) and albendazole (ALB). AREAS COVERED: All available articles regarding research related to the treatment of NCC were searched. Relevant articles were then reviewed and used as sources of information for this review. EXPERT OPINION: Anticysticercal therapy has been marked by intense controversy. Recent descriptions of spontaneous resolution of parenchymal cysticercosis with benign evolution, risks of complications and reports of no long-term benefits have reinforced the debate over the usefulness and safety of anticysticercal therapy. High interindividual variability and complex pharmacological interactions will require the close monitoring of plasma concentrations of ALB and PZQ metabolites in future trials. Given the relative scarcity of clinical trials, more comparative interventional studies - especially randomized controlled trials in long-term clinical evolution - are required to clarify the controversy over the validity of parasitic therapy in patients with NCC. PMID- 22082144 TI - Prevention of hepatorenal toxicity with Sonchus asper in gentamicin treated rats. AB - BACKGROUND: Sonchus asper possesses antioxidant capacity and is used in liver and kidney disorders. We have investigated the preventive effect of methanolic extract of Sonchus asper (SAME) on the gentamicin induced alterations in biochemical and morphological parameters in liver and kidneys of Sprague-Dawley male rat. METHODS: Acute oral toxicity studies were performed for selecting the therapeutic dose of SAME. 30 Sprague-Dawley male rats were equally divided into five groups with 06 animals in each. Group I received saline (0.5 ml/kg bw; 0.9% NaCl) while Group II administered with gentamicin 0.5 ml (100 mg/kg bw; i.p.) for ten days. Animals of Group III and Group IV received gentamicin and SAME 0.5 ml at a dose of 100 mg/kg bw and 200 mg/kg bw, respectively while Group V received only SAME at a dose of 200 mg/kg bw. Biochemical parameters including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyltransferase (gamma-GT), total cholesterol, triglycerides, total protein, albumin, creatinine, blood urea nitrogen (BUN), total bilirubin and direct bilirubin were determined in serum collected from various groups. Urinary out puts were measured in each group and also assessed for the level of protein and glucose. Lipid peroxides (TBARS), glutathione (GSH), DNA injuries and activities of antioxidant enzymes; catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) were determined in liver and renal samples. Histopathological studies of liver and kidneys were also carried out. RESULTS: On the basis of acute oral toxicity studies, 2000 mg/kg bw did not induce any toxicity in rats, 1/10th of the dose was selected for preventive treatment. Gentamicin increased the level of serum biomarkers; AST, ALT, ALP, LDH, gamma-GT, total cholesterol, triglycerides, total protein, albumin, creatinine, BUN, total and direct bilirubin; as were the urinary level of protein, glucose, and urinary output. Lipid peroxidation (TBARS) and DNA injuries increased while GSH contents and activities of antioxidant enzymes; CAT, POD, SOD decreased with gentamicin in liver and kidney samples. SAME administration, dose dependently, prevented the alteration in biochemical parameters and were supported by low level of tubular and glomerular injuries induced with gentamicin. CONCLUSION: These results suggested the preventive role of SAME for gentamicin induced toxicity that could be attributed by phytochemicals having antioxidant and free radical scavenging properties. PMID- 22082147 TI - Molecular basis for the substrate stereoselectivity in tryptophan dioxygenase. AB - Tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) are the only two heme proteins that catalyze the oxidation reaction of tryptophan (Trp) to N formylkynurenine. While human IDO is able to oxidize both L- and D-Trp, human TDO (hTDO) displays major specificity for L-Trp. In this work, we aim to interrogate the molecular basis for the substrate stereoselectivity of hTDO. Our previous molecular dynamics simulation studies of Xanthomonas campestris TDO (xcTDO) showed that a hydrogen bond between T254 (T342 in hTDO) and the ammonium group of the substrate is present in the L-Trp-bound enzyme, but not in the D-Trp-bound enzyme. The fact that this is the only notable structural alteration induced by the change in the stereo structure of the substrate prompted us to produce and characterize the T342A mutant of hTDO to evaluate the structural role of T342 in controlling the substrate stereoselectivity of the enzyme. The experimental results indicate that the mutation only slightly perturbs the global structural properties of the enzyme but totally abolishes the substrate stereoselectivity. Molecular dynamics simulations of xcTDO show that T254 controls the substrate stereoselectivity of the enzyme by (i) modulating the hydrogen bonding interaction between the NH(3)(+) group and epoxide oxygen of the ferryl-indole 2,3-epoxide intermediate of the enzyme and (ii) regulating the dynamics of two active site loops, loop(250-260) and loop(117-130), critical for substrate binding. PMID- 22082148 TI - Diffusion of ionic fluorescent probes atop polyelectrolyte brushes. AB - The lateral diffusion of ionic fluorescent molecules atop polyelectrolyte brushes was adopted to probe the distribution of counterions of the polyelectrolyte brushes. With a combination of single molecule fluorescence techniques, fluorescence correlation spectroscopy and single molecule fluorescence imaging, the lateral diffusion of the ionic probes (sulforhodamine B, rhodamine 6G) at the top of the model polyelectrolyte brushes with the opposite charges, poly([2 (methylacryloyloxyl)ethyl] trimethylammonium chloride) (PMETAC) and polystyrene sulfonate (PSS), was studied with different external salt concentrations. A huge decrease of the diffusion rate of the probes was observed at salt concentrations 2-3 orders of magnitude lower than that for any detectable change of brushes thickness could be observed. The results reflect the early collapse of the top portion of the polyelectrolyte brushes and also the penetration of the probes into the brushes due to the increase of osmotic pressure by the salt level in the solution. The diffusion of the fluorescent counterion can serve as a very sensitive probe of the structure atop the polyelectrolyte brushes. PMID- 22082146 TI - Human Papillomaviruses, p16INK4a and Akt expression in basal cell carcinoma. AB - BACKGROUND: The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC), is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC). The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients. METHODS: The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample. RESULTS: No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%), HPV100 (11,5%) and HPV15 (11,5%) all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3%) with the highest percentages (> 30%) of positive cells detected in 8 cases. A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a. CONCLUSIONS: Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15). The association of these viruses with the up regulation of p16INK4a and Akt/PI3K pathway suggests that in a subtype of BCC these viruses may exert a role in the carcinogenesis or in other, still undefined, biological property of these tumors. If this particular type of BCC reflects a different biology it will remain undisclosed until further studies on a larger number of samples will be performed. PMID- 22082149 TI - An outcomes analysis of over 200 revision surgeries for penile prosthesis implantation: a multicenter study. AB - INTRODUCTION: Inflatable penile prosthesis (IPP) implantation is a well established treatment for medically refractory erectile dysfunction, with long term reliability. Overall survival is 96% at 5 years and 60% at 15 years for primary (virgin) implantation. AIM: The aim of this study was to explore factors associated with success and complications of IPP revision surgery in a multicenter study. MAIN OUTCOME MEASURES: Reasons for revision including mechanical issues, patient dissatisfaction, corporal deformity, and supersonic transport (SST) deformity were recorded. METHODS: At four institutions, 214 clinically uninfected IPP revisions were performed between November 2000 and November 2007. Data were incomplete for 28 cases (14%). Failure-free survival was estimated using Kaplan-Meier's Meier product limit method. RESULTS: The majority of revisions were secondary to mechanical failure (N = 109; 65%) and combined erosion or infection (N = 17 + 15 = 32; 19%). Sixteen percent (N = 26) were carried out on functional uninfected prostheses secondary to patient dissatisfaction (N = 9), SST deformity (N = 10), scrotal hematoma (N = 2), or upsize revision because of corporal fibrosis (N = 5). Average age at revision was 66 years. Mean follow-up time was 55.7 months. In this study, 12 individuals required a secondary revision procedure or suffered a complication. Despite prior reports of high infection rates with revision surgery, only 5.7% of clinically uninfected and noneroded prostheses were complicated by infection or impending extrusion/erosion, following a revision washout protocol. Overall, 93% of cases were successfully revised, providing functioning IPPs. CONCLUSIONS: For this study population, component exchange followed by revision washout showed a low incidence of infection and subsequent mechanical failure. PMID- 22082151 TI - N-Directed aliphatic C-H borylation using borenium cation equivalents. AB - Highly electrophilic boron cations derived from hindered amine borane complexes have been shown to undergo intramolecular aliphatic C-H borylation. PMID- 22082152 TI - MiRNA-9 and MiRNA-200a distinguish hemangioblastomas from metastatic clear cell renal cell carcinomas in the CNS. AB - Central nervous system (CNS) tumors in von Hippel-Lindau syndrome (VHL) include hemangioblastomas and metastatic clear cell renal cell carcinomas (Met CCRCC). While these tumors often show similar histologic features, differentiating them is of significant importance as Met CCRCC are higher-grade tumors with worse prognosis. No single current immunohistochemical marker unequivocally differentiates between these two entities. MicroRNAs (miRNAs) are noncoding cellular small RNA molecules that play an important role in cancer. We hypothesized that hemangioblastomas and Met CCRCC display distinct miRNA signatures enabling their histologic differentiation. MiRNAs were profiled in 10 cases each of hemangioblastomas, Met CCRCC and primary CCRCC. Ten miRNAs had greater abundance (including miR-9 (~10-fold) and miR-135a (~7-fold)) and 39 miRNAs were lower [including miR-200a (~22-fold) and miR-200b (~12-fold)] in hemangioblastomas compared with Met CCRCC. Quantitative real-time RT-PCR in 20 hemangioblastomas and 13 Met CCRCC showed a 12-fold increase in miR-9 and a 15 fold decrease of miR-200a in hemangioblastomas compared with Met CCRCC. Finally, in situ hybridization for miR-9 in 15 hemangioblastomas and 10 Met CCRCC confirmed these results. Our data suggest that miR-9 and miR-200a can distinguish between hemangioblastomas and Met CCRCC. Further, these results may also provide insight in understanding the biology of hemangioblastomas. PMID- 22082153 TI - Optimal imaging of in vitro clot sonothrombolysis by MR-guided focused ultrasound. AB - BACKGROUND AND PURPOSE: As magnetic resonance-guided focused ultrasound (MRgFUS) sonothrombolysis relies on mechanical rather than thermal mechanisms to achieve clot lysis, thermometry is not useful for the intraoperative monitoring of clot breakdown by MRgFUS. Therefore, the purpose of this study was to evaluate the optimum imaging sequence for sonothrombolysis. METHODS: In vitro blood drawn from 6 healthy volunteers was imaged using T1, T2 spin-echo, and T2 gradient-echo (GRE) sequences both before and after sonication using an Insightec ExAblate 4000 FUS transducer. Signal intensities of the three MR imaging sequences were measured and normalized to background signal for each time point. Representative samples of the pre- and postsonication clot were also sent to pathology for hematologic analysis. RESULTS: After sonication, the clot in the treatment tube was fully lysed as evidenced by physical and hematologic evaluation. The difference between pre- and postsonicated normalized signal intensity ratios demonstrated statistical significance only on T2 and GRE sequences (P < .001). However, significant blooming artifact limited interpretation on all GRE images. CONCLUSION: T2 is the most appropriate sequence for the evaluation of mechanical MRgFUS sonothrombolysis of an in vitro clot. These findings are consistent across the oxidative states of clot up to 48 hours. PMID- 22082154 TI - Role of the 12q24.12 locus in the onset of preeclampsia: an Italian case-control study. AB - OBJECTIVE: The 12q24.12 locus has been reported to be involved in the control of many traits and also in severe diseases such as cardiovascular disease, hypertension and some immune-related disease. To our knowledge, no study has been published so far investigating the role of this locus in the pathogenesis of preeclampsia (PE). METHODS: We genotyped four single nucleotide polymorphisms (SNPs) in 12q24.12 locus in 198 preeclamptic, 224 chronic hypertensive and 265 normotensive women from Italy, to test the contribution polymorphisms/haplotypes on the onset of preeclampsia and their association with chronic hypertension. RESULTS: No association was observed for any single SNP, while a common haplotype CGTG (21% in normotensive women) revealed a possible protective effect (OR 0.64, 95% CI 0.42-0.97) against preeclampsia. CONCLUSIONS: Our data suggest that a common haplotype within 12q24.12 locus may be associated with a protective effect against preeclampsia. This observation may be linked with the potential role of this region in the control of microcirculation. To the best of our knowledge, our study is the first one that links the 12q24.12 locus with this life-threatening perinatal complication of unknown etiology. Further physiological and functional studies are needed to clarify the molecular mechanisms and pathways of preeclampsia. PMID- 22082155 TI - Simple estimation and test procedures in capture-mark-recapture mixed models. AB - The need to consider in capture-recapture models random effects besides fixed effects such as those of environmental covariates has been widely recognized over the last years. However, formal approaches require involved likelihood integrations, and conceptual and technical difficulties have slowed down the spread of capture-recapture mixed models among biologists. In this article, we evaluate simple procedures to test for the effect of an environmental covariate on parameters such as time-varying survival probabilities in presence of a random effect corresponding to unexplained environmental variation. We show that the usual likelihood ratio test between fixed models is strongly biased, and tends to detect too often a covariate effect. Permutation and analysis of deviance tests are shown to behave properly and are recommended. Permutation tests are implemented in the latest version of program E-SURGE. Our approach also applies to generalized linear mixed models. PMID- 22082156 TI - A whole genome screen for HIV restriction factors. AB - BACKGROUND: Upon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV) human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme), p21 and tetherin are well characterised. RESULTS: To identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line. CONCLUSIONS: We propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen. PMID- 22082157 TI - Do antidepressants work in patients with chronic obstructive pulmonary disease with comorbid depression? PMID- 22082158 TI - Rationale and expectations of the Pneumonia Etiology Research for Child Health (PERCH) study. PMID- 22082160 TI - Mometasone furoate/formoterol in the treatment of persistent asthma. AB - Mometasone furoate and formoterol fumarate dihydrate (MF/F) administered via metered-dose inhaler with a dose counter is a new fixed-dose combination of an inhaled corticosteroid and a long-acting beta2-agonist indicated for daily maintenance therapy in patients aged >=12 years with persistent asthma. Randomized, controlled trials have suggested that MF/F reduces asthma deteriorations while improving lung function and other measures of asthma control, including quality-of-life. Clinical safety studies lasting up to 1 year have found that MF/F has a low incidence of local and systemic side effects. PMID- 22082161 TI - Omalizumab in the treatment of asthma. AB - Omalizumab was introduced in 2003 and is the first asthma drug to target IgE, the allergic antibody that initiates the allergic cascade. Well-controlled studies and post-marketing clinical experience have shown it to be an effective and safe medication. Treatment guidelines now recommend omalizumab as an add-on option for patients with moderate-to-severe allergic asthma uncontrolled on high-dose inhaled corticosteroids and long-acting beta-agonists. Despite initial concerns, there is no evidence of any association with malignancy at this time. In our opinion, omalizumab is well-tolerated and significantly improves pulmonary function, decreases clinical symptoms and improves the quality of life in patients with uncontrolled allergic asthma. PMID- 22082162 TI - Artificial airways for the study of respiratory disease. AB - This review will focus on human cell-based experimental models to study respiratory diseases, in particular models of the large airways relevant to asthma and chronic obstructive pulmonary disease. Such models have the advantage of incorporating cells that can be derived from disease-relevant tissue and so have retained important genetic and epigenetic features that contribute to the human disease. These models can be used for mechanistic studies, target identification and validation and toxicological testing. While many models have been developed to varying degrees of sophistication, the challenge remains to develop an integrated system that recapitulates the complex cell-cell and cell matrix interactions that occur in vivo and to provide these with a 'circulation' to study the dynamics of immune and inflammatory cell influx and efflux. PMID- 22082163 TI - Targeting airway smooth muscle in airways diseases: an old concept with new twists. AB - Airway smooth muscle (ASM) manifests a hyper-responsive phenotype in airway disorders such as asthma. ASM also modulates immune responses by secreting mediators and expressing cell-surface molecules that promote recruitment of inflammatory cells to the lungs. The aim of the current article is to highlight therapeutics that may modulate ASM responses in airway disorders and exacerbations. PMID- 22082164 TI - Carbon nanotubes as delivery systems for respiratory disease: do the dangers outweigh the potential benefits? AB - Nanoparticle drug-delivery systems offer the potential for improved efficacy of treatment, and yet there are also potential risks associated with these novel therapeutic strategies. An attractive property of carbon nanotubes (CNTs) is that the tube- or fiber-like structure allows for extensive functionalization and loading of cargo. However, a large body of evidence indicates that CNTs may have adverse effects if used in drug delivery as they have been shown to cause pulmonary fibrosis and exacerbate lung disease in rodents with pre-existing lung diseases. Major factors that cause these toxic effects are the high aspect ratio, durability and residual metal content that generate reactive oxygen species. Therefore, careful consideration should be given to the possibility that lung inflammation or fibrosis could be significant side effects caused by a CNT-based drug-delivery system, thereby outweighing any potential beneficial effects of therapeutic treatment. However, functionalization of CNTs to modulate aspect ratio, biodegradability and to remove residual metals could allow for safe design of CNTs for use in drug delivery in certain circumstances. PMID- 22082165 TI - Systematic review of the effectiveness of breathing retraining in asthma management. AB - In asthma management, complementary and alternative medicine is enjoying a growing popularity worldwide. This review synthesizes the literature on complementary and alternative medicine techniques that utilize breathing retraining as their primary component and compares evidence from controlled trials with before-and-after trials. Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library electronic databases were searched. Reference lists of all publications were manually checked to identify studies not found through electronic searching. The selection criteria were met by 41 articles. Most randomized controlled trials (RCTs) of the Buteyko breathing technique demonstrated a significant decrease in beta(2)-agonist use while several found improvement in quality of life or decrease in inhaled corticosteroid use. Although few in number, RCTs of respiratory muscle training found a significant reduction in bronchodilator medication use. Where meta analyses could be done, they provided evidence of benefit from yoga, Buteyko breathing technique and physiotherapist-led breathing training in improving asthma-related quality of life. However, considerable heterogeneity was noted in some RCTs of yoga. It is reasonable for clinicians to offer qualified support to patients with asthma undertaking these breathing retraining techniques. PMID- 22082167 TI - Sarcoidosis of the upper and lower airways. AB - Sarcoidosis is a systemic granulomatous disease of undetermined etiology characterized by a variable clinical presentation and disease course. Although clinical granulomatous inflammation may occur within any organ system, more than 90% of sarcoidosis patients have lung disease. Sarcoidosis is considered an interstitial lung disease that is frequently characterized by restrictive physiologic dysfunction on pulmonary function tests. However, sarcoidosis also involves the airways (large and small), causing obstructive airways disease. It is one of a few interstitial lung diseases that affects the entire length of the respiratory tract - from the nose to the terminal bronchioles - and causes a broad spectrum of airways dysfunction. This article examines airway dysfunction in sarcoidosis. The anatomical structure of the airways is the organizational framework for our discussion. We discuss sarcoidosis involving the nose, sinuses, nasal passages, larynx, trachea, bronchi and small airways. Common complications of airways disease, such as, atelectasis, fibrosis, bullous leions, bronchiectasis, cavitary lesions and mycetomas, are also reviewed. PMID- 22082166 TI - The emerging relationship between the airway microbiota and chronic respiratory disease: clinical implications. AB - Until recently, relationships between evidence of colonization or infection by specific microbial species and the development, persistence or exacerbation of pulmonary disease have informed our opinions of airway microbiology. However, recent applications of culture-independent tools for microbiome profiling have revealed a more diverse microbiota than previously recognized in the airways of patients with chronic pulmonary disease. New evidence indicates that the composition of airway microbiota differs in states of health and disease and with severity of symptoms and that the microbiota, as a collective entity, may contribute to pathophysiologic processes associated with chronic airway disease. Here, we review the evolution of airway microbiology studies of chronic pulmonary disease, focusing on asthma, chronic obstructive pulmonary disease and cystic fibrosis. Building on evidence derived from traditional microbiological approaches and more recent culture-independent microbiome studies, we discuss the implications of recent findings on potential microbial determinants of respiratory health or disease. PMID- 22082168 TI - Mediastinal staging of non-small-cell lung cancer. AB - Accurate mediastinal staging is the hallmark of a sound thoracic oncology program. Mediastinal staging remains the most important validated tool for making treatment decisions for patients with non-small-cell lung cancer. The last few years have seen the emergence of several new techniques to improve mediastinal staging. This article summarizes the current state of the art of this rapidly evolving field. PMID- 22082170 TI - Ultrafast control of the internuclear distance with parabolic chirped pulses. AB - Recently, control over the bond length of a diatomic molecule with the use of parabolic chirped pulses was predicted on the basis of numerical calculations [Chang; et al. Phys. Rev. A 2010, 82, 063414]. To achieve the required bond elongation, a laser scheme was proposed that implies population inversion and vibrational trapping in a dissociative state. In this work we identify two regimes where the scheme works, called the strong and the weak adiabatic regimes. We define appropriate parameters to identify the thresholds where the different regimes operate. The strong adiabatic regime is characterized by a quasi-static process that requires longer pulses. The molecule is stabilized at a bond distance and at a time directly controlled by the pulse in a time-symmetrical way. In this work we analyze the degree of control over the period and elongation of the bond as a function of the pulse bandwidth. The weak adiabatic regime implies dynamic deformation of the bond, which allows for larger bond stretch and the use of shorter pulses. The dynamics is anharmonic and not time-symmetrical and the final state is a wave packet in the ground potential. We show how the vibrational energy of the wave packet can be controlled by changing the pulse duration. PMID- 22082171 TI - Interleukin (IL)-17 versus IL-27: opposite effects on tumor necrosis factor-alpha mediated chemokine production in human keratinocytes. AB - Tumor necrosis factor (TNF)-alpha is known to play a pivotal role in the pathogenesis of psoriasis. TNF-alpha has been shown to act directly on keratinocytes, thereby inducing the production of various kinds of chemokines, which contributes to the infiltration of leucocytes into the psoriatic lesions. Recent studies have shown that both interleukin (IL)-17 and IL-27 are increased in psoriatic lesional tissue. However, the interactions between TNF-alpha, IL-17 and IL-27 in chemokine production by keratinocytes have not been fully elucidated. Here, we examined in human keratinocytes how TNF-alpha, IL-17 and IL 27 affect production of chemokines that are involved in the pathogenesis of psoriasis. We found that IL-17 and IL-27 exert opposite effects on TNF-alpha mediated chemokine production. This suggests that lesional balance of IL-17 and IL-27 is involved in the recruitment of T cells, natural killer cells, neutrophils, monocytes or dendritic cells, thereby affecting inflammation in skin diseases. PMID- 22082173 TI - False-positive pregnancy tests following enterocystoplasty. AB - People with major congenital urological or neurological malformations invariably require bladder reconstruction with enterocystoplasty in early childhood. The improvement of the surgical management of these children has reflected significantly on their life expectancy. As a result, more young people with enterocystoplasty are being transitioned to adolescent clinics where they receive the usual counselling about sexual health and pregnancy risks. However, the possibility of false-positive urinary pregnancy tests in these young women remains an overlooked but essential message. The lack of awareness about this fact can result in significant patient anxiety and the potential for unnecessary interventions as exemplified by the three cases we have encountered. PMID- 22082172 TI - Percutaneous & Mini Invasive Achilles tendon repair. AB - Rupture of the Achilles tendon is a considerable cause of morbidity with reduced function following injury. Recent studies have shown little difference in outcome between the techniques of open and non-operative treatment using an early active rehabilitation programme. Meta-analyses have shown that non-operative management has increased risk of re-rupture whereas surgical intervention has risks of complications related to the wound and iatrogenic nerve injury. Minimally invasive surgery has been adopted as a way of reducing infections rates and wound breakdown however avoiding iatrogenic nerve injury must be considered. We discuss the techniques and outcomes of percutaneous and minimally invasive repairs of the Achilles tendon. PMID- 22082174 TI - Attitudes of medical students to medical leadership and management: a systematic review to inform curriculum development. AB - BACKGROUND: There is a growing acknowledgement that doctors need to develop leadership and management competences to become more actively involved in the planning, delivery and transformation of patient services. We undertook a systematic review of what is known concerning the knowledge, skills and attitudes of medical students regarding leadership and management. Here we report the results pertaining to the attitudes of students to provide evidence to inform curriculum development in this developing field of medical education. METHODS: We searched major electronic databases and citation indexes within the disciplines of medicine, education, social science and management. We undertook hand searching of major journals, and reference and citation tracking. We accessed websites of UK medical institutions and contacted individuals working within the field. RESULTS: 26 studies were included. Most were conducted in the USA, using mainly quantitative methods. We used inductive analysis of the topics addressed by each study to identity five main content areas: Quality Improvement; Managed Care, Use of Resources and Costs; General Leadership and Management; Role of the Doctor, and Patient Safety. Students have positive attitudes to clinical practice guidelines, quality improvement techniques and multidisciplinary teamwork, but mixed attitudes to managed care, cost containment and medical error. Education interventions had variable effects on students' attitudes. Medical students perceive a need for leadership and management education but identified lack of curriculum time and disinterest in some activities as potential barriers to implementation. CONCLUSIONS: The findings from our review may reflect the relatively little emphasis given to leadership and management in medical curricula. However, students recognise a need to develop leadership and management competences. Although further work needs to be undertaken, using rigorous methods, to identify the most effective and cost-effective curriculum innovations, this review offers the only currently available summary of work examining the attitudes of students to this important area of development for future doctors. PMID- 22082175 TI - Public policy, blood safety and haemovigilance. PMID- 22082176 TI - Patient consent for blood transfusion--recommendations from SaBTO. PMID- 22082177 TI - SaBTO review of blood donor selection criteria related to sexual behaviour. PMID- 22082179 TI - Protonation states of important acidic residues in the central Ca2+ ion binding sites of the Ca2+-ATPase: a molecular modeling study. AB - The P-type ATPases are responsible for the transport of cations across cell membranes. The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) transports two Ca2+ ions from the cytoplasm to the lumen of the sarco(endo)plasmic reticulum and countertransports two or three protons per catalytic cycle. Two binding sites for Ca2+ ions have been located via protein crystallography, including four acidic amino acid residues that are essential to the ion coordination. In this study, we present molecular dynamics (MD) simulations examining the protonation states of these amino acid residues in a Ca2+-free conformation of SERCA. Such knowledge will be important for an improved understanding of atomistic details of the transport mechanism of protons and Ca2+ ions. Eight combinations of the protonation of four central acidic residues, Glu309, Glu771, Asp800, and Glu908, are tested from 10 ns MD simulations with respect to protein stability and ability to maintain a structure similar to the crystal structure. The trajectories for the most prospective combinations of protonation states were elongated to 50 ns and subjected to more detailed analysis, including prediction of pK(a) values of the four acidic residues over the trajectories. From the simulations we find that the combination leaving only Asp800 as charged is most likely. The results are compared to available experimental data and explain the observed destabilization upon full deprotonation, resulting in the entry of cytoplasmic K+ ions into the Ca2+ binding sites during the simulation in which Ca2+ ions are absent. Furthermore, a hypothesis for the exchange of protons from the central binding cavity is proposed. PMID- 22082180 TI - The relationship between same-sex sexual experience, sexual distress, and female sexual dysfunction. AB - INTRODUCTION: There is little research estimating the occurrence of female sexual dysfunction (FSD) in women with same-sex sexual experience and none incorporating a key feature of standardized DSM-IV diagnoses-sexual distress. AIM: To investigate the prevalence of FSD in women with and without same-sex sexual experience and whether any effects of same-sex sexual experience on women's sexual functioning are moderated by frequency and type of sexual activity. METHODS: The sample consisted of 5,998 female individuals aged 18-49 years. Prevalence of FSD was assessed by the Female Sexual Function Index and an abbreviated version of the Female Sexual Distress Scale. Measurement of frequency and variation in sexual activity was conducted using a modified version of the Derogatis Sexual Functioning Inventory. Lifetime same-sex experience was assessed with a single question. MAIN OUTCOME MEASURES: Prevalence estimates of FSD. Odds ratios (ORs) with 95% confidence intervals (CIs) for the subsample-specific, mediating role of frequency and mode of sexual activities on FSD. RESULTS: Women with same-sex sexual experience (13.6%) engaged significantly more in all sexual activities (P < 0.01) compared with women without such experience. They further reported significantly more desire (Z = 3.1, P < 0.05) and satisfaction problems (z = 10.6, P < 0.001). When controlling patterns of sexual activities no significant effect of same-sex sexual experience on desire could be detected (OR 1.1, CI 95% 0.9-1.2, P > 0.1), whereas the significant association between same sex sexual experience and sexual dissatisfaction remained (OR 1.28, CI 95% 1.1 1.6, P < 0.05). Sexual distress was significantly more prevalent in women with same-sex sexual experience (23%) compared with their counterparts (19%). CONCLUSIONS: Same-sex sexual experience is related, both directly and indirectly, to FSD. Testing of the mediating factors underlying this association may offer important clues into the etiology of FSD in general. The results further highlight the need to consider sexual distress as a multidimensional concept. PMID- 22082181 TI - Implications of a local overproduction of tumor necrosis factor-alpha in complex regional pain syndrome. AB - OBJECTIVE: To review the implications of a local overproduction of tumor necrosis factor-alpha for the pathogenesis and treatment of complex regional pain syndrome. BACKGROUND: Elevated local production of tumor necrosis factor-alpha contributes to prolonged inflammation in the early stages of complex regional pain syndrome. Consequences could include hypoxia and necrosis of local tissues. METHODS: We conducted a review of articles published since 2000 on tumor necrosis factor-alpha in complex regional pain syndrome. RESULTS: We propose that exaggerated local inflammation, subsequent inhibition of N-type calcium channel currents in sympathetic vasoconstrictor neurons and reduced sympathetic neurotransmitter release from perivascular terminals disrupt sympathetic cutaneous vasoconstrictor activity in complex regional pain syndrome. The resultant microvascular disturbance could exacerbate inflammation in the affected limb. In addition, an underactive cholinergic anti-inflammatory pathway might lead to overproduction of tumor necrosis factor-alpha. The results of large, randomized controlled treatment studies that test the efficacy of selective anti tumor necrosis factor-alpha drugs in complex regional pain syndrome are not yet available. However, numerous small-scale studies and case reports indicate that anti-inflammatory drug treatments that directly or indirectly target tumor necrosis factor-alpha ameliorate pain and other symptoms in some cases. CONCLUSIONS: An exaggerated inflammatory cytokine cascade may contribute to sensory and autonomic disturbances in complex regional pain syndrome. Further investigation of anti-tumor necrosis factor-alpha therapy as a cost-effective treatment option for this devastating disease is required. Whether increased activity in the cholinergic anti-inflammatory pathway provides therapeutic benefits for complex regional pain syndrome also warrants further investigation. PMID- 22082182 TI - Magic carbon clusters in the chemical vapor deposition growth of graphene. AB - Ground-state structures of supported C clusters, C(N) (N = 16, ..., 26), on four selected transition metal surfaces [Rh(111), Ru(0001), Ni(111), and Cu(111)] are systematically explored by ab initio calculations. It is found that the core shell structured C(21), which is a fraction of C(60) possessing three isolated pentagons and C(3v) symmetry, is a very stable magic cluster on all these metal surfaces. Comparison with experimental scanning tunneling microscopy images, dI/dV curves, and cluster heights proves that C(21) is the experimentally observed dominating C precursor in graphene chemical vapor deposition (CVD) growth. The exceptional stability of the C(21) cluster is attributed to its high symmetry, core-shell geometry, and strong binding between edge C atoms and the metal surfaces. Besides, the high barrier of two C(21) clusters' dimerization explains its temperature-dependent behavior in graphene CVD growth. PMID- 22082183 TI - Ultrasound-guided upper extremity blocks - tips and tricks to improve the clinical practice. AB - Brachial plexus blockade in children can be used for a broad spectrum of clinical indications. Nevertheless, these regional anesthetic techniques are still underused in pediatric anesthesia that is mainly because of insufficient descriptions of the particular techniques. Ultrasound guidance enables direct visualization of neuronal and adjacent anatomical structures, the cannula, and the spread of local anesthetic. The most important issue in this context is theoretical background knowledge and intensive training of hand skills. The following review article discusses all relevant aspects of ultrasound-guided brachial plexus blockade. PMID- 22082184 TI - Age-related decrease of miRNA-92a levels in human CD8+ T-cells correlates with a reduction of naive T lymphocytes. AB - MicroRNA (miR)-17-92a expression plays a crucial role in lymphocyte ontogeny. We therefore set out to determine miR-92a expression levels in peripheral blood lymphocytes from healthy subjects to ascertain any association between these levels and ageing. We found a positive correlation between the miR-92a expression level and the percentages of RO-CD8+CD27+ (P = 0.0046) and CD3+CD8+CD62L+ (P = 0.0011). This suggests that the majority of miR-92a of CD8+ T cells is derived from naive cells, and the miR-92a expression level in CD8+ T cells declines progressively with age. These results indicate that the age-related attrition of naive T cells is linked to a reduction of miR-92a in human T -lymphocytes. Therefore, we should careful attention when evaluating human miRNA levels in T lymphocytes to use normal control values. PMID- 22082187 TI - Piriformis pyomyositis, an unusual presentation of leg pain post partum--case report and review of literature. AB - Piriformis pyomyositis is defined as a subacute infection of skeletal muscles associated with systemic infectious symptoms. In the literature it rarely occurs postpartum. We report a case of piriformis pyomyositis involving a parturient and review the published cases available in the literature. PMID- 22082186 TI - Relationship between Dietary and Other Lifestyle Habits and Cardiometabolic Risk Factors in Men. AB - BACKGROUND: Prevalence of men with cardiometabolic risk factors (CMRF) is increasing in Japan. Few studies have comprehensively examined the relation between lifestyles and CMRF. METHODS: We examined the baseline data from 3,498 male workers ages 19 to 69 years who participated in the high-risk and population strategy for occupational health promotion (HIPOP-OHP) study at 12 large-scale companies throughout Japan. The physical activity of each participant was classified according to the International Physical Activity Questionnaire (IPAQ). Dietary intake was surveyed by a semi-quantitative Food Frequency Questionnaire. We defined four CMRF in this study as follows: 1) high blood pressure (BP): systolic BP >= 130 mmHg, or diastolic BP >= 85 mmHg, or the use of antihypertensive drugs; 2) dyslipidemia: high-density lipoprotein-cholesterol concentration < 40 mg/dl, or triglycerides concentration >= 150 mg/dl, or on medication for dyslipidemia; 3) impaired glucose tolerance: fasting blood sugar concentration >=110 mg/dl; 4) obese: a body mass index >= 25 kg/m2. RESULTS: Those who had 0 to 4 CMRF accounted for 1,597 (45.7%), 1,032 (29.5%), 587 (16.8%), 236 (6.7%), and 44 (1.3%) participants, respectively, in the Poisson distribution. Poisson regression analysis revealed that independent factors that contributed to the number of CMRF were age (b = 0.020, P < 0.01), IPAQ (b = 0.091, P < 0.01), alcohol intake (ml/day) (b = 0.001, P = 0.03), percentage of protein intake (b = 0.059, P = 0.01), and total energy intake (kcal)(b = 0.0001, P < 0.01). Furthermore, alcohol intake and its frequency had differential effects. CONCLUSIONS: Alcohol intake, percent protein and total energy intake were positively associated, whereas drinking frequency and IPAQ were inversely associated, with the number of CMRF. PMID- 22082188 TI - Oligodeoxynucleotides inhibit Toll-like receptor 3 mediated cytotoxicity and CXCL8 release in keratinocytes. AB - Toll-like receptor 3 (TLR3) is an important sensor of viral infections and injury of self in keratinocytes. In this study, we stimulated primary keratinocytes with the TLR3-ligand polyI:C. This induced a toxic effect shown by up-regulation of the alarmin high-mobility group protein B1 and reduced responses in a MTT-assay. PolyI:C was a potent inducer of proinflammatory cytokines, and both these responses and the cytotoxic effects were found to be TLR3 dependent, as demonstrated by the use of siRNA for TLR3. Interestingly, co-stimulation with oligodeoxynucleotides (ODNs) inhibited all polyI:C induced effects. This inhibition was found to be mediated by the competition of endocytic uptake of polyI:C and ODNs. We have found polyI:C induced cytotoxicity and proinflammatory responses to be dependent of TLR3 and that this may be inhibited by ODNs. With these findings, we see a promising potential for ODNs in inhibiting TLR3-induced responses in inflammatory skin disorders. PMID- 22082189 TI - Improvement of antibiotic activity of Xenorhabdus bovienii by medium optimization using response surface methodology. AB - BACKGROUND: The production of secondary metabolites with antibiotic properties is a common characteristic to entomopathogenic bacteria Xenorhabdus spp. These metabolites not only have diverse chemical structures but also have a wide range of bioactivities with medicinal and agricultural interests such as antibiotic, antimycotic and insecticidal, nematicidal and antiulcer, antineoplastic and antiviral. It has been known that cultivation parameters are critical to the secondary metabolites produced by microorganisms. Even small changes in the culture medium may not only impact the quantity of certain compounds but also the general metabolic profile of microorganisms. Manipulating nutritional or environmental factors can promote the biosynthesis of secondary metabolites and thus facilitate the discovery of new natural products. This work was conducted to evaluate the influence of nutrition on the antibiotic production of X. bovienii YL002 and to optimize the medium to maximize its antibiotic production. RESULTS: Nutrition has high influence on the antibiotic production of X. bovienii YL002. Glycerol and soytone were identified as the best carbon and nitrogen sources that significantly affected the antibiotic production using one-factor-at-a-time approach. Response surface methodology (RSM) was applied to optimize the medium constituents (glycerol, soytone and minerals) for the antibiotic production of X. bovienii YL002. Higher antibiotic activity (337.5 U/mL) was obtained after optimization. The optimal levels of medium components were (g/L): glycerol 6.90, soytone 25.17, MgSO4.7H2O 1.57, (NH4)2SO4 2.55, KH2PO4 0.87, K2HPO4 1.11 and Na2SO4 1.81. An overall of 37.8% increase in the antibiotic activity of X. bovienii YL002 was obtained compared with that of the original medium. CONCLUSIONS: To the best of our knowledge, there are no reports on antibiotic production of X. boviebii by medium optimization using RSM. The results strongly support the use of RSM for medium optimization. The optimized medium not only resulted in a 37.8% increase of antibiotic activity, but also reduced the numbers of experiments. The chosen method of medium optimization was efficient, simple and less time consuming. This work will be useful for the development of X. bovienii cultivation process for efficient antibiotic production on a large scale, and for the development of more advanced control strategies on plant diseases. PMID- 22082190 TI - Solitary fibrous tumors and hemangiopericytomas of the meninges: overlapping pathological features and common prognostic factors suggest the same spectrum of tumors. AB - Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are distinct entities in the World Health Organization (WHO) classification of central nervous system (CNS) tumors while they belong to the same spectrum of tumors in other locations. Well-defined histological prognostic factors are also lacking for these tumors. In order to clarify the relationship between SFT and HPC and to find histological and immunohistochemical prognostic factors, we carried out a retrospective study in 89 patients. The following histological parameters were recorded: hypercellularity, collagenic areas, cytonuclear atypias, necrosis, mitotic count per 10 high-power fields, vasculo-nervous adherences defined by engulfment of vessel or nerve by the tumor, brain infiltration. We found overlapping histological and immunohistochemical features between SFT and HPC. The most relevant histological prognostic factors in the whole cohort for both progression-free survival (PFS) and overall survival (OS) in univariate analysis were hypercellularity, high mitotic count (>5 per 10 high power fields) and necrosis. On the basis of these results, we propose a new grading scheme for these tumors which was of pronostic value for both PFS and OS in uni- and multivariate analysis. As extent of surgery was also a prognostic factor for both PFS and OS in univariate analysis, we propose that management of SFT/HPC might be based both on quality of removal and histological grade. PMID- 22082191 TI - Mode of delivery and postpartum emotional distress: a cohort study of 55,814 women. AB - OBJECTIVE: To assess the association between mode of delivery and maternal postpartum emotional distress. DESIGN: A prospective study of women from 30 weeks of gestation to 6 months postpartum. SETTING: Pregnant women in Norway during the period 1998-2008. POPULATION: A total of 55,814 women from the Norwegian Mother and Child Cohort Study. METHODS: Emotional distress was reported in a short form of the Hopkins Symptom Checklist-25 (SCL-8) at 30 weeks of gestation and at 6 months postpartum. Information on mode of delivery was obtained from the Medical Birth Registry of Norway. MAIN OUTCOME MEASURES: Changes in SCL-8 score from 30 weeks of gestation to 6 months postpartum and presence of emotional distress at 6 months postpartum. RESULTS: Women with instrumental vaginal, emergency caesarean or elective caesarean deliveries had similar changes in SCL-8 score between 30 weeks of gestation and 6 months postpartum, as compared with women with unassisted vaginal delivery (adjusted regression coefficient, 0.00, 95% CI -0.01 to 0.01; 0.01, 95% CI 0.00-0.02; and -0.01, 95% CI -0.02 to 0.00, respectively). The corresponding odds ratios (ORs) associated with the presence of emotional distress at 6 months postpartum (SCL-8 >= 2.0) were: OR 1.01, 95% CI 0.86-1.18; OR 1.13, 95% CI 0.97-1.32; and OR 0.96, 95% CI 0.79-1.16, respectively. These estimates were adjusted for emotional distress during pregnancy and other potential confounding factors. Emotional distress during pregnancy showed the strongest association with the presence of emotional distress at 6 months postpartum (adjusted OR 14.09, 95% CI 12.77-15.55). CONCLUSIONS: Mode of delivery was not associated with a change in SCL-8 score from 30 weeks of gestation to 6 months postpartum or with the presence of emotional distress postpartum. PMID- 22082193 TI - Performance of conventional and range-separated hybrid density functionals in calculations of electronic circular dichroism spectra of transition metal complexes. AB - A number of density functionals, including 'pure' (nonhybrid) functionals, global hybrids, and range-separated hybrids, were used to calculate the electronic circular dichroism (CD) spectra of 10 tris-bidentate transition metal complexes. The results are compared to one another and to experimental CD spectra, in an effort to illustrate the shortcomings of particular approximations in time dependent density functional theory (TDDFT). The use of an origin invariant formalism to calculate magnetic transition dipole moments with the help of gauge including atomic orbitals (GIAOs) is also investigated. With valence basis sets of moderate flexibility, good agreement between GIAO results and rotatory strengths calculated from the dipole-velocity representation is obtained for selected test cases. Empirically broadened vertical CD spectra calculated with the global hybrid functionals B3LYP and PBE0 are found to agree overall the best with experimental CD spectra. PMID- 22082194 TI - p38alpha mitogen-activated protein kinase inhibitors, a patent review (2005 2011). AB - INTRODUCTION: Since the first biological factor that neutralized tumor necrosis (TNF)-alpha was brought to the market, there has been a desperate search for small molecules with the same efficacy in therapy of inflammatory disorders. One of the most promising targets is p38alpha mitogen-activated protein (MAP) kinase. This enzyme is a key player in a vast number of inflammatory and autoimmune processes. AREAS COVERED: Almost every international company doing research in drug discovery is or was involved in the development of compounds that inhibit p38alpha MAP kinase. Herein their patents and the corresponding publications are summarized. EXPERT OPINION: In the last few years, compounds have become more potent and more selective, for example, by induction of the so-called glycine flip. Furthermore, some companies are striving for selectivity with respect to isoforms. The increasing availability of rapid screening services, which include more than 400 kinases, has encouraged companies to reconsider traditional approaches. The most promising approach appears to be the development of linear binding molecules that feature a carbonyl oxygen that can enforce the glycine flip. Furthermore, recent projects increasingly target new fields of application, for example, pulmonary diseases. This might be the most important trend of the past few years. PMID- 22082195 TI - Current computer modeling cannot explain why two highly similar sequences fold into different structures. AB - The remarkable recent creation of two proteins that fold into two completely different and stable structures, exhibit different functions, yet differ by only a few amino acids poses a conundrum to those hoping to understand how sequence encodes structure. Here, computer modeling uniquely allows the characterization of not only the native structure of each minimally different sequence but also systems in which each sequence was modeled onto the fold of the alternate sequence. The reasons for the different structural preferences of two pairs of highly similar sequences are explored by a combination of structure analyses, comparison of potential energies calculated from energy-minimized single structures and trajectories produced from molecular dynamics simulations, and application of a novel method for calculating free energy differences. The sensitivity of such analyses to the choice of force field is also explored. Many of the hypotheses proposed on the basis of the nuclear magnetic resonance model structures of the proteins with 95% identical sequences are supported. However, each level of analysis provides different predictions regarding which sequence structure combination should be most favored, highlighting the fact that protein structure and stability result from a complex combination of interdependent factors. PMID- 22082196 TI - Influenza H1N1 (swine flu) vaccination: a safety surveillance feasibility study using self-reporting of serious adverse events and pregnancy outcomes. AB - AIMS: During the global H1N1 influenza A (swine flu) pandemic 2009-2010, swine flu vaccines were expeditiously licensed and a mass vaccination programme for high risk groups, including pregnant women, was introduced in the UK. This pilot active safety surveillance study was performed to establish the feasibility of rapidly monitoring the new swine flu vaccines in large patient numbers receiving or offered the vaccination under normal conditions of use within a short time frame. METHODS: A cohort design with safety data capture through modern technologies was carried out in Scotland, UK during the winter swine flu vaccination programme 2009-2010 in individuals receiving or offered the swine flu vaccination. The main outcome measures were self-reported serious adverse events (SAEs) and pregnancy outcomes. RESULTS: The cohort comprised 4066 people; 3754 vaccinated and 312 offered the vaccination but not vaccinated. There were 939 self-reported events (838 different events), 53 judged to fit SAE criteria by the investigators, with nine judged as possibly, probably or definitely vaccine related. None of the seven deaths (six in vaccinees) were judged as vaccine related. One hundred and twenty-eight women reported 130 pregnancies during the study with 117 pregnant at study start. There were reports of four miscarriages in three women and six possible congenital abnormalities in live births. CONCLUSIONS: Overall, no significant safety issues were identified. The methodology and use of modern technologies to collect safety data from large numbers of patients was successful and could be used again in similar safety studies. PMID- 22082197 TI - Total synthesis of the photoprotecting dipyrrolobenzoquinone (+)-terreusinone. AB - The first synthesis of (+)-terreusinone 1, a dipyrrolobenzoquinone with a potent UV-A protecting capability, is described. Key transformations include a one-pot Larock indolization-Sonogashira coupling reaction and the hydroamination of an unsubstituted ortho-alkynylaniline catalyzed by a cationic gold(I) complex. The synthesis proceeds in eight steps from commercially available starting materials, confirming the structure and absolute configuration of the natural product. PMID- 22082199 TI - The blackberry fruit: a review on its composition and chemistry, metabolism and bioavailability, and health benefits. AB - Blackberry (Rubus sp.) fruit contains high levels of anthocyanins and other phenolic compounds, mainly flavonols and ellagitannins, which contribute to its high antioxidant capacity and other biological activities. Blackberry phenolic composition and concentrations are known to be influenced by genetics, growing conditions, and maturation. Despite the current knowledge of their chemistry, research specific to blackberry phenolic compounds' health benefits, metabolism, bioavailability, and mechanism by which they confer health benefits is scarce. Blackberry phenolic compounds have protective effects on age-related neurodegenerative diseases and bone loss in vivo and can inhibit low-density lipoprotein and liposomal oxidation in vitro. Blackberry extracts have also exerted antimutagenic effects in vitro and in vivo by modifying cell signaling pathways and suppressing tumor promotion factors. However, the antiobesity, antidiabetic, antimicrobial, and anti-inflammatory properties of blackberry phenolic compounds need investigation. Similarly, studies that elucidate the in vivo physiologically effective concentrations of blackberry phenolic compounds are necessary. PMID- 22082200 TI - Sustained-release oxycodone tablets for moderate to severe painful diabetic peripheral neuropathy: a multicenter, open-labeled, postmarketing clinical observation. AB - OBJECTIVE: To evaluate the efficacy and safety of sustained-release (SR) oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy (DPN). Design. This was a multicenter, randomized, open labeled study. SETTING: This study was completed in 12 hospitals in China. PATIENTS: A total of 80 Chinese patients undergoing moderate to severe painful DPN. INTERVENTIONS: An initial dose of 10mg is recommended to be taken orally every 12 hours. Dose titration was done appropriately according to pain intensity and adverse reactions. OUTCOME MEASURES: Data record included days, dosage, analgesic efficacy, quality of sleep, adverse events, and combination therapy when patients were treated with SR oxycodone tablets. The continuous observation period was 6 weeks. RESULTS: After medication for 1 week, pain was significantly (P<0.01) relieved from 6.8+/-1.4 to 2.8+/-1.6. Onset time was within 45 minutes in nearly 60% of the patients, and within 1 hour in nearly 95% of that ones. More than 90% of the patients achieved stable analgesic dose within 3 days. After using SR oxycodone tablets for 1 week, sleep quality was significantly (P<0.01) improved. In week 1, the average dose of SR oxycodone tablets was 16.63+/-7.79mg. The average daily dose of most patients was about 20mg after 2 weeks. In all the enrolled patients, 38 (47.5%) had adverse reactions. No serious adverse reactions took place. CONCLUSION: The results of this clinical observation further elaborated the efficacy and safety of SR oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy in China. PMID- 22082201 TI - Modeling light trapping in nanostructured solar cells. AB - The integration of nanophotonic and plasmonic structures with solar cells offers the ability to control and confine light in nanoscale dimensions. These nanostructures can be used to couple incident sunlight into both localized and guided modes, enhancing absorption while reducing the quantity of material. Here we use electromagnetic modeling to study the resonances in a solar cell containing both plasmonic metal back contacts and nanostructured semiconductor top contacts, identify the local and guided modes contributing to enhanced absorption, and optimize the design. We then study the role of the different interfaces and show that Al is a viable plasmonic back contact material. PMID- 22082202 TI - Research on basis of reverse genetics system of a Sindbis-like virus XJ-160. AB - As a Sindbis-like virus (SINLV), XJ-160 virus was isolated from a pooled sample of Anopheles mosquitoes collected in Xinjiang, China, in 1990. Recombinant plasmid pBR-XJ160 is an infectious full-length cDNA clone of XJ-160 virus, from which rescued virus BR-XJ160 can be obtained by transcription in vitro and transfection. The BR-XJ160 virus raised in BHK-21 cells was indistinguishable from the XJ-160 virus in its biological properties, including its plaque morphology, growth kinetics and suckling mouse neurovirulence. On basis of pBR XJ160, the effects of substitutions within nonstructural protein 1 (nsP1) or nsP2 on the infectivity and pathogenesis of Sindbis virus (SINV) have been investigated. We have also confirmed the essential role of E2 glycoprotein, especially the domain of 145-150 (amino acid) aa, in SINV infection through the interaction with cellular heparan sulfate (HS). In addition, we have developed XJ 160 virus-based vector system, including replicon vector, defective helper (DH) plasmids and the packaging cell lines (PCLs). Here we provide an update of main development in the field concerned with XJ-160 virus. PMID- 22082203 TI - Sexual function in women with polycystic ovary syndrome. AB - INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrinologic disorder. Little is known about the effects of PCOS on overall sexual functioning, phases of the sexual response cycle, and sexual satisfaction. AIM: To compare the differences in sexual function between women with PCOS and controls, and to assess the relationship of serum testosterone, body mass index (BMI), hirsutism, and acne with sexual function scores in women with PCOS. METHODS: A cross-sectional analysis in which women who met the National Institute of Child Health and Human Development criteria for PCOS were compared with a group of healthy volunteers. MAIN OUTCOME MEASURES: Results from the validated Changes in Sexual Functioning Questionnaire (CSFQ) were used to assess sexual function. In women with PCOS, serum testosterone levels, BMI, self-reported hirsutism, and acne were assessed as independent variables. RESULTS: Ninety-two women with PCOS and 82 controls were studied. Based on total CSFQ scores, sexual dysfunction was present in 27.2% of cases vs. 24.4% of controls (not signifcant). Women with PCOS had a significantly lower orgasm/completion score compared with women in the control group (P < 0.001). Women with PCOS whose testosterone levels were >1 standard deviation above the mean had significantly better sexual functioning vs. those within 1 SD (P = 0.015) and those >1 SD below the mean (P = 0.033). In women with PCOS, increasing BMI was associated with a significant reduction in the orgasm/completion subdomain, but no significant associations were found in regard to acne or hirsutism. CONCLUSIONS: Women with PCOS have similar sexual functioning scores compared with controls except in regard to orgasm/completion. The subpopulation of women with PCOS whose serum testosterone levels are in the normal reproductive range are at increased risk for sexual dysfunction. PMID- 22082204 TI - L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function. AB - BACKGROUND: There are an increasing number of patients suffering from fatty liver caused by type 2 diabetes. We intended to study the preventive and therapeutic effect of L-carnitine (LC) on nonalcoholic fatty liver disease (NAFLD) in streptozotocin (STZ)-induced type 2 diabetic mice and to explore its possible mechanism. METHODS: Thirty male Kungming mice were randomly divided into five groups: control group, diabetic group, pre-treatment group (125 mg/kg BW), low dose (125 mg/kg BW) therapeutic group and high-dose (250 mg/kg BW) therapeutic group. The morphology of hepatocytes was observed by light and electron microscopy. LC and ALC (acetyl L-carnitine) concentrations in the liver were determined by high-performance liquid chromatography (HPLC). Moreover, liver weight, insulin levels and free fatty acid (FFA) and triglyceride (TG) levels in the liver and plasma were measured. RESULTS: Average liver LC and ALC levels were 33.7% and 20% lower, respectively, in diabetic mice compared to control mice (P < 0.05). After preventive and therapeutic treatment with LC, less hepatocyte steatosis, clearer crista and fewer glycogen granules in the mitochondria were observed. Decreased liver weight, TG levels, and FFA concentrations (P < 0.05) in the liver were also observed after treatment with LC in diabetic mice. Moreover, liver LC and ALC levels increased upon treatment with LC, whereas the ratio of LC and ALC decreased significantly (P < 0.01). CONCLUSION: LC supplements ameliorated fatty liver in type 2 diabetic mice by increasing fatty acid oxidation and decreasing the LC/ALC ratio in the liver. Therefore, oral administration of LC protected mitochondrial function in liver. PMID- 22082205 TI - Catalytic kinetic resolution of cyclic secondary amines. AB - The catalytic resolution of racemic cyclic amines has been achieved by an enantioselective amidation reaction featuring an achiral N-heterocyclic carbene catalyst and a new chiral hydroxamic acid cocatalyst working in concert. The reactions proceed at room temperature, do not generate nonvolatile byproducts, and provide enantioenriched amines by aqueous extraction. PMID- 22082206 TI - Evaluation of fetal nuchal translucency in 98 pregnancies at risk for severe spinal muscular atrophy: possible relevance of the SMN2 copy number. AB - OBJECTIVE: To study fetal nuchal translucency (NT) thickness as a possible early marker in fetuses at risk for severe spinal muscular atrophy (SMA). To investigate the significance of the survival motor neuron (SMN) 2 gene copy number in affected fetuses. METHODS: We performed 2D-ultrasound in 98 pregnancies at risk for SMA, all of which underwent prenatal molecular testing of the SMN1 gene. Crown-rump length (CRL) and NT measurements were obtained in all cases before chorionic villus sampling. Fetuses were diagnosed as healthy, carriers or affected according to the SMN1 molecular testing results. SMN2 copies were also tested in all affected fetuses. RESULTS: Nineteen fetuses were predicted to be affected due to the absence of the SMN1 gene, 18 of which had two SMN2 copies. Mean CRL and NT values did not differ between healthy, carrier and affected fetuses. In the remaining affected case who had only one SMN2 copy, the ultrasound examination showed a NT value of 4.98 mm and findings compatible with hypoplastic left heart. CONCLUSIONS: Most affected SMA fetuses have normal NT values. Our findings support the idea that SMN2 copy number in SMA fetuses is relevant for the development of congenital heart defects and increased NT values. PMID- 22082207 TI - Increased liver stiffness denotes hepatic dysfunction and mortality risk in critically ill non-cirrhotic patients at a medical ICU. AB - INTRODUCTION: Hepatic dysfunction is a common finding in critically ill patients on the ICU and directly influences survival. Liver stiffness can be measured by the novel method of transient elastography (fibroscan) and is closely associated with hepatic fibrosis in patients with chronic liver disease, but also is increased in patients with acute hepatitis, acute liver failure and cholestasis. We investigated liver stiffness as a potentially useful tool for early detection of patients with hepatic deterioration and risk stratification with respect to short- and long-term mortality. METHODS: We prospectively evaluated 108 consecutive critically ill patients at our medical intensive care unit (ICU) with subsequent longitudinal liver stiffness measurements (admission, Day 3, Day 7 and weekly thereafter) during the course of ICU treatment. Outcome was followed after discharge (median observation time 237 days). RESULTS: Liver stiffness could be reliably measured in 71% of ICU patients at admission (65% at Day 3, 63% at Day 7). Critically ill patients (n = 108) had significantly increased liver stiffness compared to sex- and age-matched standard care patients (n = 25). ICU patients with decompensated cirrhosis showed highest liver stiffness, whereas other critical diseases (for example, sepsis) and comorbidities (for example, diabetes, obesity) did not impact stiffness values. At admission to the ICU, liver stiffness is closely related to hepatic damage (liver synthesis, cholestasis, fibrosis markers). During the course of ICU treatment, fluid overload (renal failure, volume therapy) and increased central venous pressure (mechanical ventilation, heart failure) were major factors determining liver stiffness. Liver stiffness values > 18 kilopascal (kPa) at ICU admission were associated with increased ICU and long-term mortality, even in non-cirrhotic patients. CONCLUSIONS: Considering that liver stiffness cannot be validly measured in about 30% of ICU patients, transient elastography performed at ICU admission might be a useful tool to early identify liver dysfunction and predict mortality in critically ill patients at a medical ICU. PMID- 22082209 TI - The laboratory of clinical virology in monitoring patients undergoing monoclonal antibody therapy. AB - The relevant efficacy of monoclonal antibodies (mAbs) has resulted in the successful treatment of several diseases, although susceptibility to infections remains a major problem. This review summarizes aspects of the literature regarding viral infections and mAbs, specifically addressing the risk of infection/reactivation, the measures that can reduce this risk, and the role played by the laboratory of clinical virology in monitoring patients undergoing mAb therapy. PMID- 22082208 TI - Progressive multifocal leukoencephalopathy: an unexpected complication of modern therapeutic monoclonal antibody therapies. AB - Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the central nervous system, caused by the reactivation of the ubiquitous JC virus. PML usually occurs during severe immunosuppression, and the most common causes are represented by human immunodeficiency virus infection, lymphoproliferative disorders and other forms of cancer. Recently, the introduction of monoclonal antibodies (e.g. natalizumab, rituximab, efalizumab) in the treatment of several dysimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis and systemic lupus erythematosus, has led to an increased incidence of PML. This phenomenon has had severe consequences, leading, for example, to the withdrawal from the market of Efalizumab, and important restrictions in the use of the other compounds, all of which are characterized by high efficacy in improving prognosis and quality of life. In this review we will discuss clinical, laboratory and imaging findings of PML. In addition, proposed pathogenetic mechanisms promoting the reactivation of JC virus in the context of treatment with monoclonal antibodies will be described. PMID- 22082211 TI - Transferability of a modified embryonic stem cell test using a new endpoint for developmental neurotoxicity. AB - We developed and analyzed a new surrogate endpoint of the mouse embryonic stem cell test (EST) for developmental neurotoxicity. To determine the sensitivity, specificity, and transferability of the new endpoint, a pre-validation team from three independent laboratories optimized and standardized the protocol for neuronal differentiation of mouse embryonic stem cells (mESCs) by measuring the neuronal differentiation rates of mESCs under different culture conditions, such as the presence or absence of basic fibroblast growth factor (bFGF) in the growth media and varying lengths of culture. In addition, a component ratio of neuronal cells was measured by using flow cytometry analysis of beta-III tubulin (Tuj1) positive cells and real-time polymerase chain reaction analysis of microtubule associated protein 2 (MAP2) mRNA. Our results showed that the best growth was achieved by culturing mESCs for 12 d in N2B27 medium without bFGF or ascorbic acid. Lead (II) acetate and aroclor 1254 were used to test the usefulness of the new endpoint. When we used the known ID(50) values for lead (II) acetate in the EST model, it was classified as non-embryotoxic; however, when we used the new ID(50) values that we determined in this study, it was classified as weakly embryotoxic. Aroclor 1254 and penicillin G were also classified as weakly embryotoxic and non-embryotoxic compounds, respectively, when cardiac and neuronal differentiation ID(50) values were used. Therefore, our new surrogate endpoint for developmental neurotoxicity is not only sensitive and specific but also transferable among laboratories. PMID- 22082212 TI - Donors' perspectives on their postdonation information (PDI) event: a qualitative interview study of PDI donors. AB - BACKGROUND: Postdonation information (PDI) occurs when a donor fails to report a risk that would have resulted in deferral, but at some subsequent point is disclosed. Donors' perspectives on and perceived reasons for their PDIs have not been previously studied. STUDY DESIGN AND METHODS: A qualitative interview study was conducted with PDI, appropriately deferred (and not PDI), and accepted donors from the six REDS-II blood centers. Telephone interviews were conducted with donors using semistructured discussion guides after their most recent donation or donation attempt. Salient themes were identified within and across the three donor categories using interview recordings and notes. RESULTS: Sixty-six donors were interviewed (35 PDIs, 21 appropriately deferred, and 10 accepted). Cases could be grouped into one of three broad clusters according to the apparent primary reason for the PDI event: perceived changes in rules or application of more intensive screening procedures at this visit versus prior visit(s), issues of recall or interpretation of a question, and discrepancies in recollections of timing. CONCLUSIONS: While descriptive and demographic information exists on the numbers and types of PDI events and donors, there has never been a qualitative study exploring donation experiences and possible reasons for their PDIs. This exploratory study based on semistructured interviews of donors identified several potentially actionable areas including the need for screeners to clarify the meaning of and answers to certain questions and helping donors accurately remember the details and dates of deferrable activities. PMID- 22082213 TI - Saccade launch site as a predictor of fixation durations in reading: comments on Hand, Miellet, O'Donnell, and Sereno (2010). AB - An important question in research on eye movements in reading is whether word frequency and word predictability have additive or interactive effects on fixation durations. A fair number of studies have reported only additive effects of the frequency and predictability of a target word on reading times on that word, failing to show significant interactions. Recently, however, Hand, Miellet, O'Donnell, and Sereno (see record 2010-19099-001) reported interactive effects in a study that included the distance of the prior fixation from the target word (launch site). They reported that when the saccade into the target word was launched from very near to the word (within 3 characters), the predictability effect was larger for low frequency words, but when the saccade was launched from a medium distance (4-6 characters from the word) the predictability effect was larger for high frequency words. Hand et al. argued for the importance of including launch site in analyses of target word fixation durations. Here we describe several problems with Hand et al.'s use of analyses of variance in which launch site is divided into distinct ordinal levels. We describe a more appropriate way to analyze such data-linear mixed-effect models-and we use this method to show that launch site does not modulate the interaction between frequency and predictability in two other data sets. PMID- 22082214 TI - The locus of tool-transformation costs. AB - Transformations of hand movements by tools such as levers or electronic input devices can invoke performance costs compared to untransformed movements. This study investigated by means of the Psychological Refractory Period (PRP) paradigm at which stage of information processing such tool-transformation costs arise. We used an inversion transformation, that is, the movement of the operating hand was transformed into a spatially incompatible movement of a lever. As a basic tool transformation effect, the initiation of inverted tool movements was delayed compared to noninverted movements. Experiment 1 suggested a central (or postcentral) locus of this tool-transformation effect and ruled out a (precentral) perceptual locus. Experiments 2 and 3 confirmed the central locus and ruled out a later, motor-related stage of processing. The results show that spatially incompatible tool movements delay a capacity-limited stage of information processing, often referred to as response selection. PMID- 22082198 TI - Dronedarone in high-risk permanent atrial fibrillation. AB - BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.). PMID- 22082215 TI - Prior entry and temporal attention: cueing affects order errors in RSVP. AB - The law of prior entry states that attended objects come to consciousness more quickly than unattended ones. This has been well established in spatial cueing paradigms, where two task-relevant stimuli are presented near-simultaneously at two different locations. Here, we suggest that prior entry also plays a pivotal role in temporal attention paradigms, where stimuli appear at the same location but at distinct moments in time, in rapid serial presentation (RSVP). Specifically, we hypothesize that prior entry can explain temporal order reversals in reporting two targets from RSVP. In support of this, three experiments show that cueing attention toward either of the targets has a strong influence on order errors. We conclude that prior entry provides a viable explanation of the way in which relevant information is prioritized in RSVP. PMID- 22082216 TI - Global statistical learning in a visual search task. AB - Locating a target in a visual search task is facilitated when the target location is repeated on successive trials. Global statistical properties also influence visual search, but have often been confounded with local regularities (i.e., target location repetition). In two experiments, target locations were not repeated for four successive trials, but with a target location bias (i.e., the target appeared on one half of the display twice as often as the other). Participants quickly learned to make more first saccades to the side more likely to contain the target. With item-by-item search first saccades to the target were at chance. With a distributed search strategy first saccades to a target located on the biased side increased above chance. The results confirm that visual search behavior is sensitive to simple global statistics in the absence of trial-to trial target location repetitions. PMID- 22082217 TI - Average orientation is more accessible through object boundaries than surface features. AB - In a glance, the visual system can provide a summary of some kinds of information about objects in a scene. We explore how summary information about orientation is extracted and find that some representations of orientation are privileged over others. Participants judged the average orientation of either a set of 6 bars or 6 circular gratings. For bars, orientation information was carried by object boundary features, while for gratings, orientation was carried by internal surface features. The results showed more accurate averaging performance for bars than for gratings, even when controlling for potential differences in encoding precision for solitary objects. We suggest that, during orientation averaging, the visual system prioritizes object boundaries over surface features. This privilege for boundary features may lead to a better representation of the spatial layout of a scene. PMID- 22082218 TI - Validating clustering of molecular dynamics simulations using polymer models. AB - BACKGROUND: Molecular dynamics (MD) simulation is a powerful technique for sampling the meta-stable and transitional conformations of proteins and other biomolecules. Computational data clustering has emerged as a useful, automated technique for extracting conformational states from MD simulation data. Despite extensive application, relatively little work has been done to determine if the clustering algorithms are actually extracting useful information. A primary goal of this paper therefore is to provide such an understanding through a detailed analysis of data clustering applied to a series of increasingly complex biopolymer models. RESULTS: We develop a novel series of models using basic polymer theory that have intuitive, clearly-defined dynamics and exhibit the essential properties that we are seeking to identify in MD simulations of real biomolecules. We then apply spectral clustering, an algorithm particularly well suited for clustering polymer structures, to our models and MD simulations of several intrinsically disordered proteins. Clustering results for the polymer models provide clear evidence that the meta-stable and transitional conformations are detected by the algorithm. The results for the polymer models also help guide the analysis of the disordered protein simulations by comparing and contrasting the statistical properties of the extracted clusters. CONCLUSIONS: We have developed a framework for validating the performance and utility of clustering algorithms for studying molecular biopolymer simulations that utilizes several analytic and dynamic polymer models which exhibit well-behaved dynamics including: meta-stable states, transition states, helical structures, and stochastic dynamics. We show that spectral clustering is robust to anomalies introduced by structural alignment and that different structural classes of intrinsically disordered proteins can be reliably discriminated from the clustering results. To our knowledge, our framework is the first to utilize model polymers to rigorously test the utility of clustering algorithms for studying biopolymers. PMID- 22082219 TI - CRABP-II- and FABP5-independent all-trans retinoic acid resistance in COLO 16 human cutaneous squamous cancer cells. AB - The effect of all-trans retinoic acid (ATRA) on cutaneous squamous cell carcinomas (c-SCC) has been poorly described. Because the imbalance of CRABP-II mediated anticancer signalling and FABP5-mediated growth-promoting signalling was supposed to be related with ATRA sensitivities of cancer cells, COLO16 human c SCC cell line was selected to check underlying mechanism leading to ATRA resistance by multiple experimental approaches. The results revealed that COLO 16 cells were resistant to 15 MUm ATRA treatment. FABP5 as well as the elements related with CRABP-II signalling (CYP26A1, CYP26B1, CRABP-I, RARalpha/beta/gamma and RXRalpha/beta/gamma) and with FABP5 signalling (PPARbeta/delta) were expressed, but CRABP-II was undetectable in COLO 16 cells. 5-Aza treatment enhanced CRABP-II expression but further bisulfite sequencing PCR-DNA sequencing revealed no methylation in CRABP-II promoter region. Transfection of CRABP-II expressing plasmids or FABP5 siRNA or both successfully manipulated the level(s) of target gene expression but failed to overcome ATRA resistance in the transfectants. In conclusion, CRABP-II and FABP5 expression were imbalanced in ATRA-resistant COLO 16 cells. 5-Aza-enhanced CRABP-II expression and unmethylation in CRABP-II promoter region suggest the methylation of certain CRABP-II regulatory gene(s) in COLO 16 cells. As neither restoration of CRABP-II expression nor the increased CRABP-II versus FABP5 ratio can overcome ATRA resistance of COLO 16 cells, additional ATRA-resistant mechanism(s) may present in human c-SCCs and COLO 16 cells would be of value in addressing this issue. PMID- 22082220 TI - A novel DP2 receptor antagonist (AM-461): a patent evaluation of WO2011085033. AB - This application claims salts and crystalline forms of a previously disclosed DP2 receptor antagonist (2-[3-[2-(tert-butylsulfanylmethyl)-4-(2,2 dimethylpropanoylamino)phenoxy]-4-methoxy-phenyl]acetic acid (1)). It also claims compositions containing the free acid and its salts, especially the sodium salt and their use in the treatment of inflammatory and respiratory diseases, especially asthma. Notably, the application presents Phase I clinical data on compound (1). PMID- 22082221 TI - Microbiologic characteristics and in vitro susceptibility to antimicrobials in a large population of patients with cardiovascular implantable electronic device infection. AB - INTRODUCTION: The incidence of cardiovascular implantable electronic device (CIED) infection is steadily increasing. However, no consensus has been reached with respect to the type and duration of antimicrobial therapy in this specific population of patients. The role played by new anti-Staphylococcus agents has not been defined. The aims of this study were to describe the microbiological characteristics of a large population of patients with CIED infections and to test the in vitro susceptibility of the various strains to different antimicrobials. METHODS: Two hundred eighty-six patients with CIED infection were included. The minimal inhibitory concentrations of 9 antimicrobials, including linezolid, tigecycline, and daptomycin were measured against all strains of staphylococci isolated. RESULTS: Microbiologic confirmation was obtained in 252 (88%) patients, the vast majority were from Staphylococcus species (86%), 90% of these were coagulase negative strains and 10% were Staphylococcus aureus; 30.5% were methicillin-resistant. All strains were susceptible to vancomycin, nearly 15% of coagulase negative strains were nonsusceptible to teicoplanin, and nearly 100% of the strains were susceptible to the 3 new antimicrobials. CONCLUSIONS: In this large contemporary study, we show that Staphylococcus is by far the most common cause of CIED infections, with the majority due to coagulase negative strains. Methicillin-resistance is common in this population. Currently, we would recommend vancomycin as first-line empirical therapy. However, given that not all patients tolerate vancomycin, we believe that newer antimicrobial therapies should now be tested in clinical trials to establish their clinical effectiveness in treating patients with device infections. PMID- 22082222 TI - Acceleration of ammonium nitrite denitrification by freezing: determination of activation energy from the temperature of maximum reaction rate. AB - A reaction of ammonium nitrite in ice was investigated. Upon freezing, some nitrite is oxidized by dissolved oxygen and some nitrite reacts with ammonium to produce nitrogen and water in a denitrification reaction. The former reaction was accelerated only during freezing, and the latter one was accelerated even after the whole sample was frozen. The denitrification reaction proceeded at very low concentration in ice, which were conditions under which the reaction would not proceed in solution. The nitrogen production increased linearly with increasing initial concentration of ammonium nitrite. The concentration factor in the unfrozen solution in ice was estimated to be 50.6 when the initial concentration was 0.5 mmol dm(-3), as obtained from comparison of reaction rates in solution and in ice. A new method for determination of the activation energy is proposed that gives a value of 53 to 61 kJ mol(-1) for denitrification. The reaction order of the denitrification process is also determined using our method, and it is concluded to follow third-order kinetics. PMID- 22082223 TI - In Arabidopsis, the spatial and dynamic organization of the endoplasmic reticulum and Golgi apparatus is influenced by the integrity of the C-terminal domain of RHD3, a non-essential GTPase. AB - The mechanisms underlying the organization and dynamics of plant endomembranes are largely unknown. Arabidopsis RHD3, a distant member of the dynamin superfamily, has recently been implicated in plant ER morphology and Golgi movement through analyses of dominant-negative mutants of the putative GTPase domain in a heterologous system. Whether RHD3 is indispensable for ER architecture and what role regions other than the putative GTPase domain play in RHD3 function are unanswered questions. Here we characterized an EMS mutant, gom8, with disrupted Golgi movement and positioning and compromised ER shape and dynamics. gom8 mapped to a missense mutation in the RHD3 hairpin loop domain, causing accumulation of the mutant protein into large structures, a markedly different distribution compared with wild-type RHD3 over the ER network. Despite the GOM8 distribution, tubules fused in the peripheral ER of the gom8 mutant. These data imply that integrity of the hairpin region is important for the subcellular distribution of RHD3, and that reduced availability of RHD3 over the ER can cause ER morphology defects, but does not prevent peripheral fusion between tubules. This was confirmed by evidence that gom8 was phenocopied in an RHD3 null background. Furthermore, we established that the region encompassing the RHD3 hairpin domain and the C-terminal cytosolic domain is necessary for RHD3 function. We conclude that RHD3 is important in ER morphology, but is dispensable for peripheral ER tubulation in an endogenous context, and that its activity relies on the C-terminal region in addition to the GTPase domain. PMID- 22082225 TI - Longitudinal observation of changes in pain sensitivity during opioid tapering in patients with chronic low-back pain. AB - OBJECTIVE: Several studies have shown that exposure to opioids for short or long periods alters pain sensitivity. Little is known about changes in pain sensitivity during and after tapering of long-term prescribed opioid treatment in chronic low-back pain (cLBP) patients. DESIGN: The goal of this prospective longitudinal study was to investigate pain sensitivity in a homogeneous patient population (cLBP patients only) after tapering of long-term (17 months) opioid use and to monitor the changes in pain sensitivity for 6 months. METHODS: Pain sensitivity (thermal sensation and thermal pain thresholds in low back and nondominant hand) was measured by quantitative sensory testing (QST) at 1 day before (T1), 3 weeks after (T2), and 6 months after the start of opioid tapering (T3) in 35 patients with both cLBP and opioid medication (OP), 35 opioid-naive cLBP patients (ON), and 28 individuals with neither pain nor opioid intake (HC). RESULTS: Significant differences in heat pain thresholds were found among the three groups at all three time points (T1: P=0.001, T2: P=0.015, T3: P=0.008), but not between the two patient groups. OP patients showed lower cold pain thresholds at T2 than ON patients and HC. At T3, the heat pain thresholds of OP patients still remained lower than HC (P=0.017), while those of ON patients were normalized. CONCLUSIONS: Our findings suggest that long-term use of opioids does not reduce pain sensitivity in cLBP patients; opioid tapering may induce brief hyperalgesia that can be normalized over a longer period. PMID- 22082224 TI - Central venous catheter use in severe malaria: time to reconsider the World Health Organization guidelines? AB - BACKGROUND: To optimize the fluid status of adult patients with severe malaria, World Health Organization (WHO) guidelines recommend the insertion of a central venous catheter (CVC) and a target central venous pressure (CVP) of 0-5 cmH2O. However there are few data from clinical trials to support this recommendation. METHODS: Twenty-eight adult Indian and Bangladeshi patients admitted to the intensive care unit with severe falciparum malaria were enrolled in the study. All patients had a CVC inserted and had regular CVP measurements recorded. The CVP measurements were compared with markers of disease severity, clinical endpoints and volumetric measures derived from transpulmonary thermodilution. RESULTS: There was no correlation between the admission CVP and patient outcome (p = 0.67) or disease severity (p = 0.33). There was no correlation between the baseline CVP and the concomitant extravascular lung water (p = 0.62), global end diastolic volume (p = 0.88) or cardiac index (p = 0.44). There was no correlation between the baseline CVP and the likelihood of a patient being fluid responsive (p = 0.37). On the occasions when the CVP was in the WHO target range patients were usually hypovolaemic and often had pulmonary oedema by volumetric measures. Seven of 28 patients suffered a complication of the CVC insertion, although none were fatal. CONCLUSION: The WHO recommendation for the routine insertion of a CVC, and the maintenance of a CVP of 0-5 cmH2O in adults with severe malaria, should be reconsidered. PMID- 22082226 TI - Controlled chlorine plasma reaction for noninvasive graphene doping. AB - We investigated the chlorine plasma reaction with graphene and graphene nanoribbons and compared it with the hydrogen and fluorine plasma reactions. Unlike the rapid destruction of graphene by hydrogen and fluorine plasmas, much slower reaction kinetics between the chlorine plasma and graphene were observed, allowing for controlled chlorination. Electrical measurements on graphene sheets, graphene nanoribbons, and large graphene films grown by chemical vapor deposition showed p-type doping accompanied by a conductance increase, suggesting nondestructive doping via chlorination. Ab initio simulations were performed to rationalize the differences in fluorine, hydrogen, and chlorine functionalization of graphene. PMID- 22082227 TI - Quantitative proteomics reveal up-regulated protein expression of the SET complex associated with hepatocellular carcinoma. AB - We combined culture-derived isotope tags (CDITs) with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) to extensively survey abnormal protein expression associated with hepatocellular carcinoma (HCC) in clinical tissues. This approach yielded an in-depth quantitated proteome of 1360 proteins. Importantly, 267 proteins were significantly regulated with a fold change of at least 1.5. The proteins up-regulated in HCC tissues are involved in regulatory processes, such as the granzyme A-mediated apoptosis pathway (The GzmA pathway). The SET complex, a central component in the GzmA pathway, was significantly up-regulated in HCC tissue. The elevated expressions of all of the SET complex components were validated by Western blotting. Among them, ANP32A and APEX1 were further investigated by immunohistochemistry staining using tissue microarrays (59 cases), confirming their overexpression in tumors. The up regulation and nuclear accumulations of APEX1 was associated not only with HCC malignancy but also with HCC differentiation in 96 clinical HCC cases. Our work provided a systematic and quantitative analysis and demonstrated key changes in clinical HCC tissues. These proteomic signatures could help to unveil the underlying mechanisms of hepatocarcinogenesis and may be useful for the discovery of candidate biomarkers. PMID- 22082228 TI - Cutaneous type adult T-cell leukaemia/lymphoma successfully treated with narrowband ultraviolet B phototherapy. PMID- 22082229 TI - Carbon nanotube nucleation driven by catalyst morphology dynamics. AB - In situ observation of the carbon nanotube nucleation process accompanied by dynamic reconstruction of the catalyst particle morphology is considered within a thermodynamic approach. It reveals the driving force for the detachment of the sp(2)-carbon cap, so-called lift-off-a crucial event in nanotube growth. A continuum model and detailed atomistic calculations identify the critical factors in the lift-off process: (i) catalyst surface energy, affected by the chemisorbed carbon atoms at the exterior surface of the catalyst, exposed to the carbon feedstock; and (ii) the emergence of a pristine, high-energy facet under the sp(2)-carbon dome. This further allows one to evaluate the range of carbon feedstock chemical potential, where the lift-off process occurs, to be followed by emergence of single-walled nanotube, and provides insights into observed catalyst morphology oscillations leading to formation of multiwalled carbon nanotubes. PMID- 22082230 TI - Degarelix: an antagonist to GnRH--theoretical and treatment considerations in paraphilia. PMID- 22082231 TI - Meconium obstruction in absence of cystic fibrosis in low birth weight infants: an emerging challenge from increasing survival. AB - BACKGROUND: Meconium abnormalities are characterized by a wide spectrum of severity, from the meconium plug syndrome to the complicated meconium ileus associated with cystic fibrosis. Meconium Related Ileus in absence of Cystic Fibrosis includes a combination of highly viscid meconium and poor intestinal motility, low grade obstruction, benign systemic and abdominal examination, distended loops without air fluid levels. Associated risk factors are severe prematurity and low birth weight, Caesarean delivery, Maternal MgSO4 therapy, maternal diabetes. In the last 20 yrs a new specific type of these meconium related obstructions has been described in premature neonates with low birth weight. Its incidence has shown to increase while its management continues to be challenging and controversial for the risk of complicated obstruction and perforation. MATERIALS AND METHODS: Among 55 newborns admitted between 1992-2008 with Meconium Related Ileus as final diagnosis, data about Low Birth Weight infants (LBW < 1500 g) were extracted and compared to those of patients >= 1500 g. Hischsprung's Diseases and Cystic Fibrosis were excluded by rectal biopsy and genetic probe before discharge. A softening enema with Gastrografin was the first option whenever overt perforation was not present. Temporary stoma or trans appendiceal bowel irrigation were elected after unsuccessful enema while prompt surgical exploration was performed in perforated cases. NEC was excluded in all operated cases. Data collected were perinatal history and neonatal clinical data, radiological signs, clinical course and complications, management and outcome. RESULTS: 30 cases with BW >= 1500 g had an M/F ratio 16/14, Mean B.W. 3052 g, Mean G.A. 37 w Caesarean section rate 40%. There were 10 meconium plug syndrome, 4 small left colon syndromes, and 16 meconium ileus without Cystic Fibrosis. Five cases were born at our institution (inborn) versus 25 referred after a mean of 2, 4 Days (1-7) after birth in another Hospital (outborn). They were managed, after a Gastrografin enema with 90% success rate, by 1 temporary Ileostomy and 2 trans appendiceal irrigation. 25 cases with BW< 1500 g (LBW) had M/F ratio 11/14, Mean B.W. 818 g, Mean G.A. 27 w, Caesarean section rate 70%, assisted ventilation 16/25. There were 8 inborn and 17 outborn. Gastrografin enema was successful in 6 out 8 inborn infants only, all referred within one week from birth. There were 12 perforations mainly among late referred LBW outborn. CONCLUSIONS: Meconium Related Ileus without Cystic Fibrosis responds to conservative management and softening enema in most of mature infants. In LBW clinical course is initially benign but as any long standing bowel obstruction management may present particular challenges. Clinical and plain radiographic criteria are reliable for making diagnosis and testing for Cystic Fibrosis may not be indicated. Enema may be resolutive when performed in a proper environment. Perforated cases may be confused with NEC which is excluded by clinical history, no signs of sepsis, lab signs missing, abdominal signs missing, typical radiological signs missing. The higher complication rate is recorded among cases delivered and initially managed in Neonatal Units without co-located Surgical Facilities. Early diagnosis and aggressive medical therapy may lead to higher success rate and help avoiding surgical interventions. Surgical therapy in uncomplicated cases, unresponsive to medical management, should be minimally aggressive. PMID- 22082232 TI - Lexical representation of schwa words: two mackerels, but only one salami. AB - The present study investigated the lexical representations underlying the production of English schwa words. Two types of schwa words were compared: words with a schwa in poststress position (e.g., mackerel), whose schwa and reduced variants differ in a categorical way, and words with a schwa in prestress position (e.g., salami), whose variants differ in a noncategorical way. Participants named pseudohomophones and matched pseudowords corresponding to schwa and reduced variants of these words. Results revealed an advantage for pseudohomophones over matched pseudowords for both variants of poststress schwa words but only for schwa variants of prestress schwa words. As the pseudohomophone advantage is assumed to reflect the activation of a phonologically matching stored phonological representation, these results suggest that both variants of poststress schwa words are lexically represented while only schwa variants of prestress schwa words are. This result extends the proposal that words with two categorically distinct variants are stored in the production lexicon with 2 representations to another language and demonstrates that this 2 lexeme account does not generalize to pronunciation variants differing from one another in a noncategorical fashion. This finding challenges one of the widely shared assumption of generative models of word production: that content words have only 1 phonological representation. On the other hand, it provides further evidence in favor of another fundamental assumption of these models: that lexical representations are abstract sets of segments rather than fully detailed exemplars. PMID- 22082233 TI - Generating and evaluating options for decision making: the impact of sequentially presented evidence. AB - We examined how decision makers generate and evaluate hypotheses when data are presented sequentially. In the first 2 experiments, participants learned the relationship between data and possible causes of the data in a virtual environment. Data were then presented iteratively, and participants either generated hypotheses they thought caused the data or rated the probability of possible causes of the data. In a 3rd experiment, participants generated hypotheses and made probability judgments on the basis of previously stored general knowledge. Findings suggest that both the hypotheses one generates and the judged probability of those hypotheses are heavily influenced by the most recent evidence observed and by the diagnosticity of the evidence. Specifically, participants generated a narrow set of possible explanations when the presented evidence was diagnostic compared with when it was nondiagnostic, suggesting that nondiagnostic evidence entices participants to cast a wider net when generating hypotheses. PMID- 22082234 TI - Judge for yourself: reply to Evans and Buehner (2011). AB - In their comment, Evans and Buehner (2011) maintained that Fiedler and Kareev's (2006) conclusion that decision quality does not always increase with the size of information sample is wrong in every respect. They claimed, first, that the decision model proposed by Fiedler and Kareev is normatively incorrect and is not supported by earlier findings; second, that Fiedler and Kareev misinterpreted or misrepresented their own data, which show in fact a large-sample advantage; and third, that it is not true that small samples lead to clear data; rather, when clear data are observed people make do with small samples. In this rebuttal, we refute all these claims. First, the issue is whether the model is descriptively, not normatively, correct. Furthermore, earlier data are commensurate with our, not Evans and Buehner's, model. Second, our data do support our conclusion; it is Evans and Buehner's dismissal of some of our data that led them to their conclusions. Finally, Evans and Buehner's third point is discussed explicitly and at length in the original article. However, whereas Evans and Buehner only reiterate this point (and present it as novel), we continue from there and show that small samples are likely to result in clear data. PMID- 22082235 TI - EGCG inhibits the invasion of highly invasive CL1-5 lung cancer cells through suppressing MMP-2 expression via JNK signaling and induces G2/M arrest. AB - Tumor metastasis is the main obstacle to the treatment of lung cancer. According to previous findings, matrix metalloproteinase-2 (MMP-2) is closely correlated with metastatic potential in lung cancer. This study showed that epigallocatechin 3-gallate (EGCG), a natural polyphenol in green tea, is a potent inhibitor of MMP 2 expression. EGCG effectively suppressed the invasion and migration of highly invasive CL1-5 lung cancer cells. Gelatin zymography, Western blot analysis, and RT-PCR were used to investigate the effects of EGCG on MMP-2 expression. The effects of EGCG on cell cycle and apoptosis were determined by flow cytometry analysis. To investigate the effects of EGCG on cell migration and cell invasion, Transwell migration/invasion assays were used. EGCG downregulated MMP-2 expression at the transcriptional level in CL1-5 cells. Moreover, the treatment of CL1-5 cells with EGCG caused downregulation of c- Jun N-terminal kinase (JNK), resulting in repression of the translocation of transcriptional factors, Sp1, and NF-kappaB, from the cytosol into the nucleus. In addition, EGCG significantly and synergistically enhanced the antitumor effects of the clinical drug, docetaxel, in CL1-5 cells. Further, EGCG induced G2/M arrest at dosages higher than those of suppression in cell invasion in CL1-5 cells. These results reveal that EGCG might decrease MMP-2 mRNA expression through JNK signaling, further suggesting that a combination of EGCG and docetaxel may be a promising strategy to help increase the efficacy of docetaxel in suppressing metastasis in lung cancer cells. In addition, EGCG may suppress cell proliferation in CL1-5 cells through inducing G2/M arrest. PMID- 22082236 TI - Impact of catheter ablation on quality of life in patients with atrial fibrillation. PMID- 22082237 TI - Synthesis of (-)-swainsonine and (-)-8-epi-swainsonine by the addition of allenylmetals to chiral alpha,beta-alkoxy sulfinylimines. AB - The asymmetric synthesis of (-)-swainsonine and (-)-8-epi-swainsonine is reported through the addition of either the allenylzinc or the allenyl lithio cyanocuprate reagents derived from [3-(methoxymethoxy)prop-1-ynyl]trimethylsilane to enantiopure alpha,beta-dialkoxy N-tert-butanesulfinylimines derived from d erythronolactone. PMID- 22082238 TI - Potential role for elevated maternal enzymatic antioxidant status in Andean protection against altitude-associated SGA. AB - Oxidative stress has been implicated in the uteroplacental ischemia characteristic of preeclampsia and small-for-gestational-age (SGA) birth, both of which are more common at high (>2500 m) vs low altitude. Since Andeans are protected relative to Europeans from the altitude-associated rise in SGA, we asked whether alterations in maternal antioxidant status or oxidative stress contributed to their protection. Enzymatic antioxidant (erythrocyte catalase and superoxide dismutase [SOD]) activity and a plasma marker of lipid peroxidation (8 iso-PGF2alpha) were measured during pregnancy and in the non-pregnant state in Andean or European residents of low (400 m) or high altitude (3600-4100 m). Pregnancy and altitude increased catalase and/or SOD activity to a greater extent in Andeans than Europeans. 8-iso-PGF2alpha levels were independent of altitude and pregnancy. SOD was lower in mothers of SGA infants at weeks 20 and 36. Our findings are consistent with the possibility that elevated enzymatic antioxidant activity contributes to Andean protection against altitude-associated SGA. PMID- 22082239 TI - A two-year randomized trial of obesity treatment in primary care practice. AB - BACKGROUND: Calls for primary care providers (PCPs) to offer obese patients behavioral weight-loss counseling have not been accompanied by adequate guidance on how such care could be delivered. This randomized trial compared weight loss during a 2-year period in response to three lifestyle interventions, all delivered by PCPs in collaboration with auxiliary health professionals (lifestyle coaches) in their practices. METHODS: We randomly assigned 390 obese adults in six primary care practices to one of three types of intervention: usual care, consisting of quarterly PCP visits that included education about weight management; brief lifestyle counseling, consisting of quarterly PCP visits combined with brief monthly sessions with lifestyle coaches who instructed participants about behavioral weight control; or enhanced brief lifestyle counseling, which provided the same care as described for the previous intervention but included meal replacements or weight-loss medication (orlistat or sibutramine), chosen by the participants in consultation with the PCPs, to potentially increase weight loss. RESULTS: Of the 390 participants, 86% completed the 2-year trial, at which time, the mean (+/-SE) weight loss with usual care, brief lifestyle counseling, and enhanced brief lifestyle counseling was 1.7+/ 0.7, 2.9+/-0.7, and 4.6+/-0.7 kg, respectively. Initial weight decreased at least 5% in 21.5%, 26.0%, and 34.9% of the participants in the three groups, respectively. Enhanced lifestyle counseling was superior to usual care on both these measures of success (P=0.003 and P=0.02, respectively), with no other significant differences among the groups. The benefits of enhanced lifestyle counseling remained even after participants given sibutramine were excluded from the analyses. There were no significant differences between the intervention groups in the occurrence of serious adverse events. CONCLUSIONS: Enhanced weight loss counseling helps about one third of obese patients achieve long-term, clinically meaningful weight loss. (Funded by the National Heart, Lung, and Blood Institute; POWER-UP ClinicalTrials.gov number, NCT00826774.). PMID- 22082240 TI - A case study on co-exposure to a mixture of organic solvents in a Tunisian adhesive-producing company. AB - OBJECTIVES: to assess environmental and biological monitoring of exposure to organic solvents in a glue-manufacturing company in Sfax, Tunisia. METHODS: Exposure of volunteer workers, in the solvented glue-work-stations, in the control laboratory and in the storage rooms of the finished products, was assessed through indoor-air and urine measurements. Informed consent of the workers was obtained. RESULTS AND DISCUSSION: The exposure indexes were found with high values in the solvented workshop as well as in the control laboratory and were respectively, 8.40 and 3.12. These indexes were also correlated with hexane and toluene indoor air concentrations. As to urine, the obtained results for the 2,5-hexandione and hippuric acid, metabolites of hexane and toluene, respectively, were in accord with the indoor-air measurements, with an average of 0.46 mg/l and 1240 mg/g of creatinine. CONCLUSION: This study assessed for the first time biological exposure to organic solvents used in Tunisian adhesive industries. Although values are likely to underestimate true exposure levels, some figures exceed European and American occupational exposure guidelines. PMID- 22082241 TI - Clot lysis time and the risk of myocardial infarction and ischaemic stroke in young women; results from the RATIO case-control study. AB - Reduced overall fibrinolytic capacity increases the risk of myocardial infarction (MI), as demonstrated in studies with predominantly male participants. We determined the influence of altered fibrinolysis on the risk of MI and ischaemic stroke (IS) in young women. The RATIO (Risk of Arterial Thrombosis In relation to Oral contraceptives) study is a population-based case-control study including young women with MI (n=203), IS (N=175) and 638 matched healthy controls. Fibrinolytic potential was determined with a tissue factor/tissue plasminogen activator induced clot-lysis assay. Odds ratios (OR) adjusted for cardiovascular risk factors were obtained with logistic regression. Clot-lysis time (CLT) was divided into tertiles based on the control group (T1-T3), with T2 as reference. Hypofibrinolysis (prolonged CLT) was associated with an increase in risk of MI (T3 vs. T2, OR 2.8; 95%confidence interval [CI] 1.7-4.7). Hyperfibrinolysis (decreased CLT) had no clear effect (T1 vs. T2, OR 1.6; 95% CI 0.9-2.9). Hypofibrinolysis did not affect the risk of IS (T3 vs. T2, OR 1.5; 95% CI 0.7 3.0), whereas hyperfibrinolysis increased this risk (T1 vs. T2, OR 4.1; 95% CI 2.1-8.0). Oral contraceptive use and smoking further increased these risks. Hypofibrinolysis increases the risk for MI in young women, a finding similar to previous studies. Counter-intuitively, hyperfibrinolysis increased the risk of IS four-fold, which suggests that MI and IS have different aetiologies. PMID- 22082242 TI - Discovery of active enhancers through bidirectional expression of short transcripts. AB - BACKGROUND: Long-range regulatory elements, such as enhancers, exert substantial control over tissue-specific gene expression patterns. Genome-wide discovery of functional enhancers in different cell types is important for our understanding of genome function as well as human disease etiology. RESULTS: In this study, we developed an in silico approach to model the previously reported phenomenon of transcriptional pausing, accompanied by divergent transcription, at active promoters. We then used this model for large-scale prediction of non-promoter associated bidirectional expression of short transcripts. Our predictions were significantly enriched for DNase hypersensitive sites, histone H3 lysine 27 acetylation (H3K27ac), and other chromatin marks associated with active rather than poised or repressed enhancers. We also detected modest bidirectional expression at binding sites of the CCCTC-factor (CTCF) genome-wide, particularly those that overlap H3K27ac. CONCLUSIONS: Our findings indicate that the signature of bidirectional expression of short transcripts, learned from promoter-proximal transcriptional pausing, can be used to predict active long-range regulatory elements genome-wide, likely due in part to specific association of RNA polymerase with enhancer regions. PMID- 22082243 TI - DARC alleles and Duffy phenotypes in African Americans. AB - BACKGROUND: The DARC (Duffy blood group, chemokine receptor) gene encodes for a transmembrane glycoprotein that functions as a chemokine transporter, is a receptor for Plasmodium vivax and P. knowlesi, and expresses the Duffy blood group antigens (Fy). The Fy(a-b-) phenotype found in people of African descent is typically associated with a -67t>c mutation in the 5'-untranslated region (UTR), which prevents red blood cells being invaded by P. vivax and P. knowlesi. The aim of this study was to establish DARC allele frequencies in an African American blood donor cohort, determine a phylogenetic tree for DARC, and compare human and Neandertal DARC genes. STUDY DESIGN AND METHODS: The DARC nucleotide sequence of 54 African American blood donors was determined from genomic DNA. Heterozygous substitutions were resolved by sequencing of haplotype-specific amplifications. A phylogenetic tree for DARC was established using the neighbor-joining method with Pan troglodytes as root. RESULTS: A total of 108 haplotypes of the DARC gene could be unambiguously determined from nucleotide position -300 in the 5' UTR to +300 in the 3' UTR. Eleven different alleles were found, including the clinically relevant FY*A, FY*B, FY*B-67C, FY*B298A, and FY*X alleles. All phenotype predictions based on genotypes matched the serologically determined phenotypes exactly: 52% Fy(a-b-), 28% Fy(a-b+), and 20% Fy(a+b-). CONCLUSIONS: The nucleotide sequencing approach using one amplicon is a practical genotyping method for DARC and allows the determination of haplotypes even in heterozygous constellations. We developed a phylogenetic tree for DARC alleles and postulated a distinct FY*B allele as ancestral for the extant DARC alleles in humans. PMID- 22082245 TI - Burnout among foreign-born and native Swedish women: a longitudinal study. AB - The authors of this study addressed burnout experiences (generally defined as chronic depletion of an individual's energetic resources') over time in relation to other factors (e.g., distress, sleep difficulties, job demands, etc.) among foreign-born women and Swedish native women living in Stockholm. The study design was a longitudinal panel survey with two waves one year apart. In the first wave, 3,616 of 6,000 randomly selected women took part, and 2,300 of the initial 3,616 women also participated in the second wave; 427 were foreign-born women, and 1,873 were Swedish native women. Baseline/emerging distress, emerging sleep difficulties, worsening general social support, job demands at baseline/escalating during the assessment period, emerging unemployment, constraints in social support at work, and sustained/emerging financial strain were associated with future burnout, regardless of background. More foreign-born women than Swedish native women reported burnout, with these differences maintained at one-year follow-up. The factors related to burnout were largely the same in both groups, but smoking and cardiovascular disease were related to burnout only among foreign-born women. Younger age, job demands, and working hours were associated with burnout among Swedish native women. The authors found that the women had concurrent problems such as burnout, distress, and sleep problems, but foreign background was not independently related to burnout. PMID- 22082244 TI - Substance use behavior among early-adolescent Asian American girls: the impact of psychological and family factors. AB - Confronting developmental tasks and challenges associated with bridging two different cultures, Asian American adolescent girls face increasing risks for substance use. Identifying risk and protective factors in this population is essential, particularly when those factors can inform preventive programs. Guided by family interaction theory, the present cross-sectional study explored the associations of psychological and familial factors with use of alcohol, prescription drugs, and other drugs among early-adolescent Asian American girls. Between August 2007 and March 2008, 135 pairs of Asian American girls (mean age 13.21 years, SD=0.90) and their mothers (mean age 39.86 years, SD=6.99) were recruited from 19 states that had significant Asian populations. Girls and mothers each completed an online survey. Relative to girls who did not use substances, girls who did had higher levels of depressive symptoms, perceived peer substance use, and maternal substance use. Multiple logistic regression modeling revealed that they also had significantly lower levels of body satisfaction, problem-solving ability, parental monitoring, mother-daughter communication, family involvement, and family rules about substance use. Household composition, acculturation, and academic achievement were not associated with girls' substance use. These findings point to directions for substance abuse prevention programming among Asian American girls. PMID- 22082246 TI - Purposiveness and leisure-time physical activity in women in early midlife. AB - Physical activity in early midlife has important implications for women's health. The present cross-sectional study investigated the relation of purposiveness to leisure-time physical activity, as mediated by health investment, in a sample of women in early midlife. Participants were 211 women between the ages of 35 and 45 years (mean 40.55 years, SD = 3.11) who responded to the second wave of the study of Midlife Development in the United States. Participants were originally selected by means of a nationally representative random-digit-dialing procedure. A structural equation analysis of data with latent variables was conducted with MPLUS. Purposiveness was indexed by measures of purpose in life, personal growth, and future planning. Health investment was indexed by thought and effort committed to health and the extent to which individuals worked hard to stay healthy. Leisure-time physical activity was indexed by both moderate and vigorous leisure-time activity. Results, controlling for sociodemographic factors, showed that purposiveness was associated with more physical activity and that the relation between purposiveness and leisure-time physical activity was fully mediated by health investment. These results suggest that women with a sense of purpose may be better able to achieve acceptable levels of physical activity. PMID- 22082247 TI - Return to work outcomes of the Redesigning Daily Occupations (ReDO) program for women with stress-related disorders--a comparative study. AB - Stress-related disorders are a frequent cause for sick leave, with consequences such as great distress and adverse economic effects for the affected person and substantial costs for society. Identifying effective interventions that facilitate return to work is thus important. The aim of this study was to evaluate the effectiveness of the 16-week Redesigning Daily Occupations program as a work rehabilitation method for Swedish women with stress-related disorders. The authors of this study hypothesized that, compared to women who got Care as Usual, 12 months after completed rehabilitation a larger proportion of the Redesigning Daily Occupations women would have returned to work, and they would have less sick leave, perceive less stress, and have greater self-esteem. Forty two women entered the Redesigning Daily Occupations intervention and a matched comparison group received Care as Usual. The data, collected between 2007 and 2010, consisted of registry information and questionnaires targeting socio demographics, perceived stress, and self-esteem. The findings partly verified the hypotheses. A larger proportion of the Redesigning Daily Occupations women returned to work and they decreased their sick leave and increased their self esteem more than the Care as Usual group, but the groups did not differ in stress reduction. Thus, the Redesigning Daily Occupations seems to be a promising work rehabilitation method for women with stress-related disorders. PMID- 22082248 TI - Women's expectations of healthcare professionals in case of intimate partner violence in Serbia. AB - Women who have experienced intimate partner violence use health care services more often than non-abused women, but it is unclear what they expect from physicians in relation to their intimate partner violence experience. In this study the authors explored whether women in Serbia expect physicians to help them after having experienced intimate partner violence, what kind of help the women expected, and if none, why none is expected. The authors of this study conducted structured interviews with 120 women who visited six primary healthcare centres. Quantitative data were analyzed using descriptive statistics, while qualitative data were analyzed applying content analyses. The majority of women (81.7%) expected healthcare professionals to help them in the event of intimate partner violence, mainly through giving advice, information, contacting other institutions, services, and providing understanding and support. Fewer women expected help in the form of documenting violence and contacting police. Only a minority (8.3%) did not expect help, noting that intimate partner violence is beyond the scope of healthcare professionals' interest or competencies, and/or that violence was a private problem, while 10% were unsure about the role of physicians in the case of intimate partner violence. The majority of women in this study expected help with intimate partner violence. Physicians should be aware of these expectations and how to provide support to women experiencing intimate partner violence. PMID- 22082249 TI - Ebselen is a new skin depigmenting agent that inhibits melanin biosynthesis and melanosomal transfer. AB - We assessed the ability of ebselen, a glutathione peroxidase mimic, to reduce pigmentation in various models. In murine B16 melanocytes, 25 MUm ebselen inhibited melanogenesis and induced a depolymerisation of actin filaments. In co cultures of B16 melanocytes with BDVII keratinocytes, a pretreatment of melanocytes with ebselen resulted in a strong inhibition of melanosome transfer to keratinocytes, as shown under optical and electron microscopy. In reconstructed epidermis, topical 0.5% ebselen led to a twofold decrease of melanin without affecting the density of active melanocytes. A similar result was obtained with topical 0.5% ebselen in black guinea pig ears. Ebselen induced a decrease of epidermal melanin parallel to a localisation of melanin and melanosomes in the basal layer. Ebselen appears as a new depigmenting compound that inhibits melanin synthesis and melanosome transfer to keratinocytes. PMID- 22082250 TI - Effect of sleep-inducing music on sleep in persons with percutaneous transluminal coronary angiography in the cardiac care unit. AB - AIM AND OBJECTIVE: The study compared the effect of earplug-delivered sleep inducing music on sleep in persons with percutaneous transluminal coronary angiography in the cardiac care unit. BACKGROUND: Diverse types of music have been claimed to improve sleeping elsewhere, but relatively little is known in South Korea. Most studies investigating the effect of sleep-inducing music on sleep have involved persons with insomnia, even though many persons with cardiovascular disease in the intensive care unit suffer from sleeping problems. There is a need to investigate the effect of sleep-inducing music on sleep disorders in persons with percutaneous transluminal coronary angiography in the cardiac care unit. DESIGN: An experimental research design was used. METHODS: Data collection was conducted in the cardiac care unit of K University Hospital in D city, from 3 September-4 October 2010. Fifty-eight subjects participated and were randomly assigned to the experimental group (earplug-delivered sleep inducing music for 52 min beginning at 10:00 pm, while wearing an eyeshield, n = 29) and the control group (no music, but earplugs and eyeshield worn, n = 29). The quantity and quality of sleep were measured using questionnaires at 7 am the next morning for each group. RESULTS: Participants in the experimental group reported that the sleeping quantity and quality were significantly higher than control group (t = 3.181, p = 0.002, t = 5.269, p < 0.001, respectively). CONCLUSION: Sleep-inducing music significantly improved sleep in patients with percutaneous transluminal coronary angiography at a cardiac care unit. Offering earplugs and playing sleep-inducing music may be a meaningful and easily enacted nursing intervention to improve sleep for intensive care unit patients. RELEVANCE TO CLINICAL PRACTICE: Nurses working at cardiac care unit can use music to improve sleeping in clients with percutaneous transluminal coronary angiography. PMID- 22082251 TI - Whole mitochondrial genome sequencing of domestic horses reveals incorporation of extensive wild horse diversity during domestication. AB - BACKGROUND: DNA target enrichment by micro-array capture combined with high throughput sequencing technologies provides the possibility to obtain large amounts of sequence data (e.g. whole mitochondrial DNA genomes) from multiple individuals at relatively low costs. Previously, whole mitochondrial genome data for domestic horses (Equus caballus) were limited to only a few specimens and only short parts of the mtDNA genome (especially the hypervariable region) were investigated for larger sample sets. RESULTS: In this study we investigated whole mitochondrial genomes of 59 domestic horses from 44 breeds and a single Przewalski horse (Equus przewalski) using a recently described multiplex micro array capture approach. We found 473 variable positions within the domestic horses, 292 of which are parsimony-informative, providing a well resolved phylogenetic tree. Our divergence time estimate suggests that the mitochondrial genomes of modern horse breeds shared a common ancestor around 93,000 years ago and no later than 38,000 years ago. A Bayesian skyline plot (BSP) reveals a significant population expansion beginning 6,000-8,000 years ago with an ongoing exponential growth until the present, similar to other domestic animal species. Our data further suggest that a large sample of wild horse diversity was incorporated into the domestic population; specifically, at least 46 of the mtDNA lineages observed in domestic horses (73%) already existed before the beginning of domestication about 5,000 years ago. CONCLUSIONS: Our study provides a window into the maternal origins of extant domestic horses and confirms that modern domestic breeds present a wide sample of the mtDNA diversity found in ancestral, now extinct, wild horse populations. The data obtained allow us to detect a population expansion event coinciding with the beginning of domestication and to estimate both the minimum number of female horses incorporated into the domestic gene pool and the time depth of the domestic horse mtDNA gene pool. PMID- 22082252 TI - Modeling molecular acidity with electronic properties and Hammett constants for substituted benzoic acids. AB - Molecular acidity is an important physiochemical property essential in many fields of molecular studies, but an efficient and reliable computational approach to make accurate predictions is still missing. In this work, based on our previous studies to use gas phase electronic properties such as molecular electrostatic potential and valence natural atomic orbitals of the acidic atom and leaving proton, we demonstrate here that different approaches can be employed to tackle this problem. To that end, we employ 196 singly, doubly, and triply substituted benzoic acids for the study. We show that two different approaches are possible, one focusing on the carboxyl group through its localized electronic properties and the other on the substituting groups via Hammett constants and their additivity rule. Our present results clearly exhibit that with the linear models built from the singly substituted species, one can accurately predict the pK(a) values for the doubly and triply substituted species with both of these two approaches. The predictions from these approaches are consistent with each other and agree well with the experimental data. These intrinsically different approaches are the two manifestations of the same molecular acidity property, both valid and complementary to each other. PMID- 22082253 TI - Using previous models to bias structural learning in the hierarchical BOA. AB - Estimation of distribution algorithms (EDAs) are stochastic optimization techniques that explore the space of potential solutions by building and sampling explicit probabilistic models of promising candidate solutions. While the primary goal of applying EDAs is to discover the global optimum or at least its accurate approximation, besides this, any EDA provides us with a sequence of probabilistic models, which in most cases hold a great deal of information about the problem. Although using problem-specific knowledge has been shown to significantly improve performance of EDAs and other evolutionary algorithms, this readily available source of problem-specific information has been practically ignored by the EDA community. This paper takes the first step toward the use of probabilistic models obtained by EDAs to speed up the solution of similar problems in the future. More specifically, we propose two approaches to biasing model building in the hierarchical Bayesian optimization algorithm (hBOA) based on knowledge automatically learned from previous hBOA runs on similar problems. We show that the proposed methods lead to substantial speedups and argue that the methods should work well in other applications that require solving a large number of problems with similar structure. PMID- 22082254 TI - Upper abdominal cytoreduction and thoracoscopy for advanced epithelial ovarian cancer: unanswered questions and the impact on treatment. AB - Gynaecological oncologists, by conducting Phase II and III chemotherapy trials, have sought to improve survival in women with epithelial ovarian cancer. The greatest impact on survival has been the use of intraperitoneal chemotherapy in women who have had all visible disease removed. No change in drug regimen has had an impact on survival equivalent to that associated with complete cytoreduction or the use of intraperitoneal chemotherapy. Interestingly, these two treatment modalities (complete cytoreduction and intraperitoneal chemotherapy) have not been universally adopted. Most often it is the inability to achieve optimal cytoreduction in the upper abdomen that defines the limit of the cytoreductive effort, and ultimately the integration of intraperitoneal chemotherapy. The importance of identifying disease outside the abdominal cavity, along with achieving complete cytoreduction, is paramount, if the use of intraperitoneal chemotherapy is to be logically integrated in treatment algorithms for women with advanced-stage epithelial ovarian cancer. This report summarises pertinent literature on upper abdominal cytoreduction, discusses surgical techniques and introduces new data on women with epithelial ovarian cancer undergoing thoracoscopy, suggesting consideration of its incorporation into the surgical management of advanced epithelial ovarian cancer. PMID- 22082255 TI - Endovascular palliation of AVM-associated intractable trigeminal neuralgia via embolization of the artery of the foramen rotundum. AB - OBJECTIVE: Trigeminal neuralgia is rarely caused by arteriovenous malformations of the posterior fossa. Embolization of aberrant vessels can provide symptomatic relief; however, embolization is not always technically possible, and its effects can be temporary. Embolization of the nerve's blood supply could reduce its excitability and provide pain relief. SETTING: The study was set in an academic tertiary care center. STUDY DESIGN: The study was designed as a report of a clinical case. SUMMARY: The authors report the case of a 13-year-old girl with a large, unruptured posterior fossa arteriovenous malformation (AVM) presented with left-sided V2-division trigeminal neuralgia. She had undergone multiple previous embolizations of feeding vessels from the anterior inferior cerebellar artery with temporary relief of her symptoms. Embolization of the middle meningeal artery was attempted, but the vessel's tortuosity precluded safe catheterization. Instead, the artery of the foramen rotundum, which had minimal contribution to the AVM nidus, was embolized with Onyx copolymer. The patient had immediate cessation of her neuralgia, with a small area of hypesthesia above her left cheek. Complete pain relief lasted for 8 months, followed by a return of mild dysesthesia episodes not requiring intervention. CONCLUSION: This case may represent a new method of palliative treatment for AVM-associated trigeminal neuralgia, or potentially trigeminal neuralgia of other etiologies. Based on this case's success, a prospective study using additional provocative testing with intraarterial lidocaine is proposed. PMID- 22082256 TI - Application of ordinal logistic regression analysis in determining risk factors of child malnutrition in Bangladesh. AB - BACKGROUND: The study attempts to develop an ordinal logistic regression (OLR) model to identify the determinants of child malnutrition instead of developing traditional binary logistic regression (BLR) model using the data of Bangladesh Demographic and Health Survey 2004. METHODS: Based on weight-for-age anthropometric index (Z-score) child nutrition status is categorized into three groups-severely undernourished (< -3.0), moderately undernourished (-3.0 to 2.01) and nourished (>=-2.0). Since nutrition status is ordinal, an OLR model proportional odds model (POM) can be developed instead of two separate BLR models to find predictors of both malnutrition and severe malnutrition if the proportional odds assumption satisfies. The assumption is satisfied with low p value (0.144) due to violation of the assumption for one co-variate. So partial proportional odds model (PPOM) and two BLR models have also been developed to check the applicability of the OLR model. Graphical test has also been adopted for checking the proportional odds assumption. RESULTS: All the models determine that age of child, birth interval, mothers' education, maternal nutrition, household wealth status, child feeding index, and incidence of fever, ARI & diarrhoea were the significant predictors of child malnutrition; however, results of PPOM were more precise than those of other models. CONCLUSION: These findings clearly justify that OLR models (POM and PPOM) are appropriate to find predictors of malnutrition instead of BLR models. PMID- 22082258 TI - Noniterative exact solution to the phase problem in optical imaging implemented with scanning probe microscopy. AB - An object is characterized by its amplitude and phase. However, when acquiring optical data about such an object, using a recording medium such as a camera, phase information is lost. Crystallography experienced a breakthrough in phase retrieval for large molecular entities by Max Perutz's introduction of "heavy atoms" using the method of isomorphous replacement. The availability of scanning probe microscopy and its full integration with optical microscopy allows us to apply these X-ray concepts to implement "heavy atom" restoration of phase in optical phase retrieval. In analogy to the heavy atom method, we acquire Fourier intensities in place of an X-ray diffraction pattern, and in place of the heavy atom, we utilize a nanometrically translatable point source of light based on the propagating field of a cantilevered near-field scanning optical microscopic (NSOM) probe controlled by an atomic force microscope (AFM). This integration of NSOM/AFM technology with far-field imaging achieves robust phase retrieval independent of external parameters, leading to 3D optical imaging. The methodology has super-resolution potential, and thus, heavy atom restoration of phase with super-resolution (HARPS) shows the potential of transparently integrated scanning probe microscopy with optical and other imaging modalities such as electron or ion optical imaging. PMID- 22082257 TI - Poly(2-aminoethyl methacrylate) with well-defined chain length for DNA vaccine delivery to dendritic cells. AB - Poly(2-aminoethyl methacrylate) (PAEM) homopolymers with defined chain length and narrow molecular weight distribution were synthesized using atom transfer radical polymerization (ATRP), and a comprehensive study was conducted to evaluate the colloidal properties of PAEM/plasmid DNA polyplexes, the uptake and subcellular trafficking of polyplexes in antigen-presenting dendritic cells (DCs), and the biological performance of PAEM as a potential DNA vaccine carrier. PAEM of different chain length (45, 75, and 150 repeating units) showed varying strength in condensing plasmid DNA into narrowly dispersed nanoparticles with very low cytotoxicity. Longer polymer chain length resulted in higher levels of overall cellular uptake and nuclear uptake of plasmid DNA, but shorter polymer chains favored intracellular and intranuclear release of free plasmid from the polyplexes. Despite its simple chemical structure, PAEM transfected DCs very efficiently in vitro in media with or without serum and led to phenotypic maturation of DCs. When a model antigen-encoding ovalbumin plasmid was used, transfected DCs stimulated the activation of naive CD8(+) T cells to produce high levels of interferon-gamma. The efficiency of transfection, DC maturation, and CD8(+) T cell activation showed varying degrees of polymer chain-length dependence. These structurally defined cationic polymers may have much potential as efficient DNA vaccine carriers and immunostimulatory adjuvants. They may also serve as a model material system for elucidating structural and intracellular mechanisms of polymer-mediated DNA vaccine delivery. PMID- 22082259 TI - Lifestyle risk management--a qualitative analysis of women's descriptions of taking hormone therapy following surgically induced menopause. AB - AIM: This article is a report of a study that examined how women describe their decisions in relation to the use of menopausal hormone therapy following surgical menopause. BACKGROUND: Women who have had a surgically induced menopause generally experience more intense menopausal symptoms than natural menopause and are regularly prescribed menopausal hormone therapy. Since 2002 the risks associated with this therapy have been widely reported. METHOD: This study is a qualitative analysis of semi-structured interviews between March and May 2009 with 30 participants who had experienced surgical menopause and were, or had in the past, taken menopausal hormone therapy. This was a community sample recruited in Christchurch, New Zealand. A risk management theoretical approach underpinned the analysis. FINDINGS: The womens' descriptions of managing the risks associated with menopausal therapy fell into two main themes: Life has to go on and Waiting for someone to tell me. All these women had either made an active decision to continue on treatment because of the impact of menopausal symptoms or took their doctor's advice to continue. A less dominant theme but one that was also evident was Relying on my body to get me through in which the women had decided to discontinue treatment because they regarded it as unnatural. CONCLUSION: The study provided insights into how women utilize an experiential reasoning process to manage the health and lifestyle risks associated with taking menopausal hormone therapy. Nurses need to be aware of how this process influences women's reasoning processes when working with women following surgical menopause. PMID- 22082261 TI - Folding of human telomerase RNA pseudoknot using ion-jump and temperature-quench simulations. AB - Globally RNA folding occurs in multiple stages involving chain compaction and subsequent rearrangement by a number of parallel routes to the folded state. However, the sequence-dependent details of the folding pathways and the link between collapse and folding are poorly understood. To obtain a comprehensive picture of the thermodynamics and folding kinetics we used molecular simulations of coarse-grained model of a pseudoknot found in the conserved core domain of the human telomerase (hTR) by varying both temperature (T) and ion concentration (C). The phase diagram in the [T,C] plane shows that the boundary separating the folded and unfolded state for the finite 47-nucleotide system is relatively sharp, implying that from a thermodynamic perspective hTR behaves as an apparent two-state system. However, the folding kinetics following single C-jump or T quench is complicated, involving multiple channels to the native state. Although globally folding kinetics triggered by T-quench and C-jump are similar, the kinetics of chain compaction are vastly different, which reflects the role of initial conditions in directing folding and collapse. Remarkably, even after substantial reduction in the overall size of hTR, the ensemble of compact conformations are far from being nativelike, suggesting that the search for the folded state occurs among the ensemble of low-energy fluidlike globules. The rate of unfolding, which occurs in a single step, is faster upon C-decrease compared to a jump in temperature. To identify "hidden" states that are visited during the folding process we performed simulations by periodically interrupting the approach to the folded state by lowering C. These simulations show that hTR reaches the folded state through a small number of connected clusters that are repeatedly visited during the pulse sequence in which the folding or unfolding is interrupted. The results from interrupted folding simulations, which are in accord with non-equilibrium single-molecule folding of a large ribozyme, show that multiple probes are needed to reveal the invisible states that are sampled by RNA as it folds. Although we have illustrated the complexity of RNA folding using hTR as a case study, general arguments and qualitative comparisons to time resolved scattering experiments on Azoarcus group I ribozyme and single molecule non-equilibrium periodic ion-jump experiments establish the generality of our findings. PMID- 22082260 TI - Analysis of oxygen/glucose-deprivation-induced changes in SUMO3 conjugation using SILAC-based quantitative proteomics. AB - Transient cerebral ischemia dramatically activates small ubiquitin-like modifier (SUMO2/3) conjugation. In cells exposed to 6 h of transient oxygen/glucose deprivation (OGD), a model of ischemia, SUMOylation increases profoundly between 0 and 30 min following re-oxygenation. To elucidate the effect of transient OGD on SUMO conjugation of target proteins, we exposed neuroblastoma B35 cells expressing HA-SUMO3 to transient OGD and used stable isotope labeling with amino acids in cell culture (SILAC) to quantify OGD-induced changes in levels of specific SUMOylated proteins. Lysates from control and OGD-treated cells were mixed equally, and HA-tagged proteins were immunoprecipitated and analyzed by 1D SDS-PAGE-LC-MS/MS. We identified 188 putative SUMO3-conjugated proteins, including numerous transcription factors and coregulators, and PIAS2 and PIAS4 SUMO ligases, of which 22 were increased or decreased more than +/-2-fold. In addition to SUMO3, the levels of protein-conjugated SUMO1 and SUMO2, as well as ubiquitin, were all increased. Importantly, protein ubiquitination induced by OGD was completely blocked by gene silencing of SUMO2/3. Collectively, these results suggest several mechanisms for OGD-modulated SUMOylation, point to a number of signaling pathways that may be targets of SUMO-based signaling and recovery from ischemic stress, and demonstrate a tightly controlled crosstalk between the SUMO and ubiquitin conjugation pathways. PMID- 22082262 TI - Greater resting heart rate variability is associated with orgasms through penile vaginal intercourse, but not with orgasms from other sources. AB - INTRODUCTION: Resting heart rate variability (HRV), a marker of parasympathetic activity, is a predictor of health and longevity. Better erectile function is associated with greater resting HRV (assessed by high frequency power [HF]), and in both sexes, penile-vaginal intercourse (PVI) is the only sexual behavior consistently associated with indices of better physical and mental health, including greater resting HRV (assessed by standard deviation [SD] of heart rate [HR]). AIMS: To examine the hypotheses that greater frequency of orgasms attained through PVI (for women, without additional simultaneous clitoral stimulation; vaginal orgasm) are associated with greater resting HRV. A differential hypothesis is that HRV measures will be unrelated to orgasmic frequency from noncoital sexual activities. METHODS: Coitally experienced men and women (N = 143) had their heart rate measured for 5 minutes and reported the frequency of various sexual behaviors and corresponding orgasms in a recent representative month. MAIN OUTCOME MEASURES: Partial correlations and analyses of covariance controlling for social desirability responding were used to examine the associations of sexual activities with time and frequency domains of HRV. RESULTS: For men, greater resting SD of HR was associated with greater PVI orgasm frequency. For women, greater resting SD of HR was associated with any vaginal orgasm. These findings remained after controlling for cohabitation. Sexual activities were unrelated to HF. Lifetime number of PVI partners was unrelated to SD of HR and HF. CONCLUSIONS: Findings are discussed in the context of orgasms through PVI enhancing HRV, and greater parasympathetic tone favoring the capacity to engage in PVI, and in the case of women, to reach vaginal orgasm. The possibility of healthier people having greater resting HRV and more frequent orgasms through specifically PVI is also considered. PMID- 22082263 TI - Translational research in sepsis - an ultimate challenge? AB - In the era of evidence-based medicine, large, randomized, controlled, multicenter studies represent the "summit of evidence". In contrast to specialties like cardiology, the majority of randomized, controlled trials in critical care medicine, however, have failed to demonstrate a survival benefit; notably, despite encouraging results from experimental and phase-II clinical studies. The difficulty in translating our theoretical knowledge into successful multicenter randomized, controlled trials and subsequent treatment recommendations may represent one reason, why the mortality of septic shock still averages between 40-60%, although our knowledge about the underlying pathophysiology has considerably increased and international guidelines have widely been implemented. The present article elucidates some of the difficulties in translating research from bench to bedside. PMID- 22082264 TI - Cranberry proanthocyanidins: natural weapons against periodontal diseases. AB - Cranberry ( Vaccinium macrocarpon ) is known to have a beneficial effect on several aspects of human health. Proanthocyanidins (PACs), the most abundant flavonoids extracted from red cranberry fruits, have been reported to possess antimicrobial, antiadhesion, antioxidant, and anti-inflammatory properties. Recent in vitro studies have shown that cranberry PACs may be potential therapeutic agents for the prevention and management of periodontitis, an inflammatory disease of bacterial origin affecting tooth-supporting tissues. After presenting an overview of cranberry phytochemicals and their potential for human health benefits, this review will focus on the effects of cranberry PACs on connective tissue breakdown and alveolar bone destruction, as well as their potential for controlling periodontal diseases. Possible mechanisms of action of cranberry PACs include the inhibition of (i) bacterial and host-derived proteolytic enzymes, (ii) host inflammatory response, and (iii) osteoclast differentiation and activity. Given that cranberry PACs have shown interesting properties in in vitro studies, clinical trials are warranted to better evaluate the potential of these molecules for controlling periodontal diseases. PMID- 22082265 TI - PVI's inconvenient truths: lights out for dormant reconnection? PMID- 22082266 TI - Role of Epac proteins in mechanisms of cAMP-dependent immunoregulation. AB - This review presents observations on the role of Epac proteins (exchange protein directly activated by cAMP) in immunoregulation mechanisms. Signaling pathways that involve Epac proteins and their domain organization and functions are considered. The role of Epac1 protein expressed in the immune system cells is especially emphasized. Molecular mechanisms of the cAMP-dependent signal via Epac1 are analyzed in monocytes/macrophages, T-cells, and B-lymphocytes. The role of Epac1 is shown in the regulation of adhesion, leukocyte chemotaxis, as well as in phagocytosis and bacterial killing. The molecular cascade initiated by Epac1 is examined under conditions of antigen activation of T-cells and immature B lymphocytes. PMID- 22082267 TI - Whole Genome Methylation Scanning Based on phi29 Polymerase Amplification. AB - Identifying differences in DNA methylation is critical to understanding how epigenetics influences gene expression during processes such as development. Here, we propose a method that employs a single, methylation-sensitive restriction endonuclease of choice, to produce discrete pools of methylated and unmethylated DNA from the same sample. A pool of restriction fragments representing unmethylated regions of the genome is first obtained by digestion with a methylation-sensitive endonuclease. The restriction-digested DNA is then concatamerized in the presence of stuffer-adaptor DNA, which prevents interference from originally unmethylated DNA by blocking the ends of the restriction fragments. The concatamerized DNA is amplified by phi29 polymerase to remove methylation marks, and again digested with the same endonuclease to produce a pool of DNA fragments representing methylated portions of the genome. The two pools of DNA fragments thus obtained can be analyzed by end-sequencing or hybridization to a genomic array. In this report we detail a proof of concept experiment that demonstrates the feasibility of our method. PMID- 22082268 TI - Influence of placental mannose/n-acetyl glucosamine-binding proteins on the interaction of insulin and insulin-like growth factors with their receptors. AB - Placenta is a source of carbohydrate-binding proteins that function as molecular scavengers, but they could also be involved in interactions that assist in metabolic control. Mannose/N-acetyl-glucosamine (Man/GlcNAc)-binding proteins from placenta were isolated and their reactivity towards placental insulin and insulin-like growth factor receptors (IR and IGF-Rs) was analyzed. The lectins reduced the binding of insulin and IGF-I in a dose-dependent manner, while almost no effect was observed on the binding of IGF-II. The shape of the inhibition curves changed, suggesting altered binding specificity. The presence of sugar could not reverse completely the effect of the lectins, implicating both lectin sugar and protein-protein conformational recognition. Since biological molecules in our experimental system were those that are in close relation in vivo, placental Man/GlcNAc-specific lectins may be regarded as potential allosteric modulators of ligand-receptor interactions in a system of homologous ligands, selectively affecting only binding to tyrosine kinase type receptors (IR and IGF 1R). PMID- 22082269 TI - Influence of proteasome inhibitor bortezomib on the expression of multidrug resistance genes and Akt kinase activity. AB - The goal of this work was to study the mechanisms of ABC family transport proteins' regulation by a new-generation antitumor drug - the proteasome inhibitor bortezomib (Velcade). ABC transporters determine the multidrug resistance of tumor cells (MDR). We confirmed our previously discovered observation that bortezomib affects the expression of genes involved in the formation of MDR (ABCB1 gene, also known as MDR1, and ABCC1-MRP1), reducing the amount of their mRNA. This effect was found to depend on Akt kinase activity: the Akt activity inhibitor Ly 294002 increased the amount of MRP1 mRNA in KB 8-5 cells. It was also shown that bortezomib increased the amount of Akt kinase phosphorylated form in cell lines of malignant cells KB 8-5 and K 562/i-S9 that overexpressed ABCB1 transporter (Pgp), and did not affect the amount of activated Akt in the corresponding wild-type cells. When exposed to bortezomib, selection of resistant to it cell variants was much faster for a Pgp-overexpressing cell population (compared to wild-type cells). It is shown that bortezomib affects the amount of MRP1 gene mRNA, relocating the multifunctional protein YB-1, dependent on Akt activity, from cytoplasm to nuclei of MCF-7 breast cancer cells. The data indicate that the transcriptional activity of YB-1 might be one of the mechanisms that determine the effect of bortezomib on the amount of MRP1 gene mRNA. PMID- 22082270 TI - Telomerase activity in the bats Hipposideros armiger and Rousettus leschenaultia. AB - Telomerase activity was examined in two species of bat, Hipposideros armiger and Rousettus leschenaultia, which have similar body mass and lifespan but differ in use of hibernation. We found that telomerase activity was present in all tissues sampled, but it was greater in metabolically active tissues such as liver, spleen, and kidney. Of special interest is the raised activity found in the heterothermic bat H. armiger, and the hibernating bats having raised values for spleen, heart, and kidney. These findings show that maintenance of high levels of telomerase is an essential part of the regulation of cellular activities during hibernation. PMID- 22082271 TI - Mitochondria-targeted plastoquinone derivative SkQ(1) decreases ischemia reperfusion injury during liver hypothermic storage for transplantation. AB - The ability of the mitochondria-targeted plastoquinone derivative 10-(6' plastoquinonyl)decyl triphenylphosphonium (SkQ(1)) to decrease ischemia reperfusion injury in isolated liver during hypothermic storage (HS) was studied. Rat liver was stored for 24 h at 4 degrees C without or in the presence of 1 MUM SkQ(1) with following reperfusion for 60 min at 37 degrees C. The presence in the storage medium of SkQ(1) significantly decreased spontaneous production of reactive oxygen species and intensity of lipid peroxidation in the liver during HS and reperfusion. The GSH level after HS in solution with SkQ(1) was reliably higher, but reperfusion leveled this effect. At all stages of experiment the presence of SkQ(1) did not prevent the decrease of antioxidant enzyme activities such as catalase, GSH peroxidase, GSH reductase, and glucose-6-phosphate dehydrogenase. The addition of SkQ(1) to the storage medium improved energetic function of the liver, as was revealed in increased respiratory control index of mitochondria and ATP level. SkQ(1) exhibited positive effect on the liver secretory function and morphology after HS as revealed in enhanced bile flow rate during reperfusion and partial recovery of organ architectonics and state of liver sinusoids and hepatocytes. The data point to promising application of mitochondria-targeted antioxidants for correction of the ischemia-reperfusion injury of isolated liver during long-term cold storage before transplantation. PMID- 22082272 TI - Selenoprotein dSelK in Drosophila elevates release of Ca2+ from endoplasmic reticulum by upregulating expression of inositol 1,4,5-tris-phosphate receptor. AB - dSelK (G-rich), a homolog of human and mouse SelK, is one of three selenoproteins in Drosophila melanogaster. It is the only trans-membrane selenoprotein in D. melanogaster integrated into both the endoplasmic reticulum (ER) membrane and the Golgi apparatus. The gene expression profile of Drosophila Schneider 2 (S2) cells after the dsRNA interference (dsRNAi) targeting of dSelK was examined with the GeneChip Drosophila Genome 2.0 Array (Affymetrix), a high-density oligonucleotide microarray encompassing nearly the full Drosophila genome. The results showed that the transcriptional expression of eight genes whose proteins are located on (or related to) the ER or the Golgi apparatus was highly induced or repressed by the dsRNAi treatment. The mRNA levels of the inositol 1,4,5-tris-phosphate receptor (IP3 receptor), whose gene product is integrated into the ER membrane and regulates the release of Ca2+ from the ER to the cytosol, were significantly downregulated. In contrast, the expression of inositol 1,4,5-tris-phosphate kinase 1, which is a cytosolic protein with opposing functions to the IP3 receptor, was significantly upregulated. Quantitative real-time PCR verified these results. The concentration of intracellular free Ca2+ of the Drosophila S2 cells was significantly decreased after the knockdown of dSelK, whereas overexpression of dSelK significantly increased the intracellular free Ca2+ concentration. These results indicate that dSelK in D. melanogaster is involved in regulating the release of Ca2+ from the ER to the cytosol and may play important roles in the signal transduction pathways involving Ca2+ mobilization. PMID- 22082273 TI - Identification of latent periodicity in domains of alkaline proteases. AB - Internal repeats in protein sequences have wide-ranging implications for the structure and function of proteins. A keen analysis of the repeats in protein sequences may help us to better understand the structural organization of proteins and their evolutionary relations. In this paper, a mathematical method for searching for latent periodicity in protein sequences is developed. Using this method, we identified simple sequence repeats in the alkaline proteases and found that the sequences could show the same periodicity as their tertiary structures. This result may help us to reduce difficulties in the study of the relationship between sequences and their structures. PMID- 22082274 TI - Antiviral resistance mutations potentiate HBV surface antigen-induced transcription of hfgl2 prothrombinase gene. AB - Antiviral resistance mutations in the hepatitis B virus (HBV) polymerase (pol) gene have been demonstrated to play an important role in the progression of liver disease and the development of hepatocellular carcinoma. The HBV pol gene overlaps the S gene encoding surface antigen (HBsAg). Previous studies from our laboratory have shown that HBV core protein (HBc) and X protein (HBx), but not HBV S protein (HBs), promote hfgl2 prothrombinase transcription. To investigate whether the nucleotide (nucleoside)-induced resistant mutations of HBs potentiate transcription of hfgl2 prothrombinase gene, we generated two mutant HB expression constructs harboring rtM204V/sI195M or rtM204I/sW196L mutations. Two mutant expression plasmids were co-transfected with hfgl2 promoter luciferase-reporter plasmids and beta-galactosidase plasmid in CHO cells and HepG2 cells, respectively. Luciferase assay showed that the rtM204I/V mutant HBs could activate the transcription of hfgl2 promoter compared with the wild type HBs. Site-directed mutagenesis and further experiment (co-transfection) demonstrated that transcription factor Ets translocated to its cognate cis-element in the hfgl2 promoter. The results show that mutated HBs caused by antiviral drug resistance induce transcription of the hfgl2 gene dependent on the transcription factor Ets. PMID- 22082275 TI - Differential inhibition/inactivation of mitochondrial complex I implicates its alteration in malignant cells. AB - Methylglyoxal strongly inhibited mitochondrial respiration of a wide variety of malignant tissues including sarcoma of mice, whereas no such significant effect was noted on mitochondrial respiration of normal tissues with the exception of cardiac cells. This inhibition by methylglyoxal was found to be at the level of mitochondrial complex I (NADH dehydrogenase) of the electron transport chain. L Lactaldehyde, which is structurally and metabolically related to methylglyoxal, could protect against this inhibition. NADH dehydrogenase of submitochondrial particles of malignant and cardiac cells was inhibited by methylglyoxal. This enzyme of these cells was also inactivated by methylglyoxal. The possible involvement of lysine residue(s) for the activity of NADH dehydrogenase was also investigated by using lysine-specific reagents trinitrobenzenesulfonic acid (TNBS) and pyridoxal 5' phosphate (PP). Inactivation of NADH dehydrogenase by both TNBS and PP convincingly demonstrated the involvement of lysine residue(s) for the activity of the sarcoma and cardiac enzymes, whereas both TNBS and PP failed to inactivate the enzymes of skeletal muscle and liver. Together these studies demonstrate a specific effect of methylglyoxal on mitochondrial complex I of malignant cells and importantly some distinct alteration of this complex in cancer cells. PMID- 22082276 TI - Interaction of transketolase from human tissues with substrates. AB - The Michaelis constant values for substrates of transketolase from human tissues were determined over a wide range of substrate concentrations. It is shown that K(m) values determined by other authors are significantly overestimated and explained why this is so. PMID- 22082277 TI - DNase, RNase, and phosphatase activities of antibodies formed upon immunization by DNA, DNase I, and DNase II. AB - Relative DNase, RNase (efficiency of hydrolysis of ribo- and deoxyribooligonucleotides (ON)), and phosphatase (removal of the ON 5' terminal phosphate) catalytic activities of antibodies (AB) obtained after rabbit immunization by DNA, DNase I, and DNase II were compared. It is shown that electrophoretically homogeneous preparations of polyclonal AB from non-immunized rabbits did not exhibit such activities. Immunization of rabbits by DNA, DNase I, and DNase II results in generation of IgG abzymes that exhibit high activity in the ON hydrolysis reaction and even higher activity in cleavage of 5' terminal phosphate of ON. In this case K(m) values for supercoiled plasmid DNA and ON found in reactions of their AB-dependent nuclease hydrolysis and phosphatase cleavage of 5' terminal phosphate differ by 2-4 orders of magnitude. This shows that nuclease and phosphatase activities belong to different abzyme fractions within polyclonal AB. Thus, in this work data indicative of the possibility of a formation of antibodies exhibiting phosphatase activity after immunization of animals with DNA, DNase I, and DNase II, were obtained for the first time. Possible reasons for production of AB with phosphatase activity after immunization of rabbits with these immunogens are discussed. PMID- 22082278 TI - Charge transport anisotropy in n-type disk-shaped triphenylene tris(aroyleneimidazole)s. AB - Two novel n-type disk-shaped molecules containing a triphenylene core and three fused naphthaleneimide imidazole or peryleneimide imidazole "arms" are synthesized and characterized. The n-type charge carrier mobilities of these molecules are evaluated by both field effect transistors and space-charge limited current measurements, which exhibit drastically different mobility anisotropy. A strong correlation between film morphology and the charge transport behavior is established by X-ray scattering and atomic force microscopic analyses. PMID- 22082279 TI - Peripheral doses in patients undergoing Cyberknife treatment for intracranial lesions. A single centre experience. AB - BACKGROUND: Stereotactic radiosurgery/radiotherapy procedures are known to deliver a very high dose per fraction, and thus, the corresponding peripheral dose could be a limiting factor for the long term surviving patients. The aim of this clinical study was to measure the peripheral dose delivered to patients undergoing intracranial Cyberknife treatment, using the MOSFET dosimeters. The influence of the supplemental shielding, the number of monitor units and the collimator size to the peripheral dose were investigated. METHODS: MOSFET dosimeters were placed in preselected anatomical regions of the patient undergoing Cyberknife treatment, namely the thyroid gland, the nipple, the umbilicus and the pubic symphysis. RESULTS: The mean peripheral doses before the supplemental shielding was added to the Cyberknife unit were 51.79 cGy, 13.31 cGy and 10.07 cGy while after the shielding upgrade they were 38.40 cGy, 10.94 cGy, and 8.69 cGy, in the thyroid gland, the umbilicus and the pubic symphysis, respectively. The increase of the collimator size corresponds to an increase of the PD and becomes less significant at larger distances, indicating that at these distances the PD is predominate due to the head leakage and collimator scatter. CONCLUSION: Weighting the effect of the number of monitor units and the collimator size can be effectively used during the optimization procedure in order to choose the most suitable treatment plan that will deliver the maximum dose to the tumor, while being compatible with the dose constraints for the surrounding organs at risk. Attention is required in defining the thyroid gland as a structure of avoidance in the treatment plan especially in patients with benign diseases. PMID- 22082280 TI - Effects of co-existing alpha-thalassaemia in sickle cell disease on hydroxycarbamide therapy and circulating nucleic acids. PMID- 22082281 TI - A pilot feasibility trial of allocation of freshest available red blood cells versus standard care in critically ill patients. AB - BACKGROUND: Prolonged storage of red blood cells (RBCs) may increase posttransfusion adverse events in critically ill patients. We aimed to evaluate in intensive care unit (ICU) patients 1) the feasibility of allocating freshest available compatible RBCs versus standard care and 2) the suitability of this approach in the design of a large randomized controlled trial (RCT). STUDY DESIGN AND METHODS: Eligible patients from two adult ICUs were randomly assigned to receive either the freshest available compatible RBCs or the standard care (the oldest compatible available RBCs) for all transfusions during their ICU stay. Study group allocation was concealed from patients and bedside clinicians, but the transfusion service was unblinded. The study endpoints were the feasibility of the study procedures, including success of the ICU Web randomization, the ICU staff blinding, and the correct delivery of the RBC units by the transfusion service in accordance with the allocated study group. In addition, we measured the difference in age of RBC units between the two groups. RESULTS: During a 3 month period, 177 RBC units were delivered to 51 patients. All study procedures, including randomization, blinding, and delivery of blood in accordance with the study group were successful. The mean (+/-SD) of the mean age of the RBC received by each patient was lower in the "fresher blood" group compared with the standard care group (12.1 [+/-3.8] days vs. 23 [+/-8.4] days; p<0.001). CONCLUSION: Randomized delivery of the freshest available RBCs versus standard care to ICU patients who were prescribed transfusion for clinical reasons is feasible, with a clinically relevant degree of storage duration separation achievable between the two study groups. These findings support the feasibility of a future large pragmatic RCT. PMID- 22082282 TI - Cancer of the body of the uterus: trends in mortality and incidence in England, 1985-2008. AB - OBJECTIVE: To report on trends in mortality and incidence for uterine cancer in England, 1985-2008. DESIGN: Database analysis. SETTING: England. POPULATION: Data sets of English national mortality and cancer registration statistics. METHODS: Analysis of data from death certificates with a mention of malignant neoplasm of corpus uteri or malignant neoplasm of uterus without specification of part, and analysis of incidence data from cancer registries in England. MAIN OUTCOME MEASURES: Age-adjusted and age-specific trends in rates. RESULTS: Mortality rates in the UK declined from 41.3 per million women in 1985 until about 1999 (30.0 per million), and then increased to 35.9 per million in 2008. Incidence rates for those aged 55 years and over showed little or no change from 1985 to the early 1990s, but then increased: for example, for women aged 60-64 years, the rates per million women in 1985, 1993, 2001 and 2008 were, respectively, 448, 461, 647 and 728. Rates for younger women showed a decline, followed by an increase: for example, for women aged 50-54 years the corresponding rates were 290, 254, 267 and 294. Over the period 2001-2008, the age-adjusted average annual percentage increase was 2.55% per annum (95% CI 2.13-2.98%). The increase in incidence rates, observed from the 1990s, preceded the increase in mortality by about 10 years. CONCLUSIONS: After many years of declining rates, uterine cancer has become more common in the first decade of this century. One possible contributor to this increase may be an association with the increase in body mass index in women, but other causes are possible and are discussed. PMID- 22082283 TI - Azole resistance in Aspergillus: a growing public health menace. PMID- 22082285 TI - Report from Eurobiofilms 2011. AB - A considerable number of the world?s leading biofilm scientists are located in Denmark, and given the small size of Denmark it must to be the country with most biofilm researchers per capita! It was therefore appropriate that the Second European Biofilm Conference, Eurobiofilms 2011, was held in Copenhagen, Denmark. The conference was organized by the European Society of Clinical Microbiology and Infectious Diseases (ECSMID) Study Group on Biofilms (ESGB), and aimed to cover basic and clinical aspects of biofilms in order to encourage synergistic interdisciplinary interactions. Therefore, both basic biofilm science and clinically related biofilm science were presented at the joint keynote lectures, and the basic biofilm science symposia as well as clinically related biofilm science symposia were run in parallel. The main program was preceded by four workshops comprising: microfluid systems and confocal laser scanning microscopy; new techniques for visualization of biofilms; animal models of biofilm infections; and molecular diagnostics of biofilm bacteria. The number of attendees exceeded 300, who were from 31 countries on six continents, and more than 200 abstracts were submitted. The conference was opened by a warm welcome from Niels Hoiby (University of Copenhagen, Denmark), the president of the conference. PMID- 22082286 TI - Examining the requirements for nucleoporins by HIV-1. AB - A hallmark of HIV type 1 and other lentiviruses is their ability to infect and replicate in nondividing cells by commandeering host nuclear transport factors. During the early stages of infection, this is expected to permit the safe passage of viral preintegration complexes (PICs) through nuclear pores. Numerous nuclear transport factors have been identified as essential for HIV-1 infection by genome wide small interfering RNA screens, and many of these are currently under investigation. Here, using knockdown studies, Matreyek and Engelman further characterize the importance of transportin-3 and nuclear pore complex component nucleoporin 153 for the early stages of HIV-1 infection and show that these two proteins operate synergistically. Also, as was previously observed for transportin-3, they show that the requirement of nucleoporin 153 for PIC nuclear entry is determined by the HIV-1 Capsid protein. The refinement of the list of key nuclear pore complex and transport proteins required for PIC entry, along with a better understanding of the specific mechanisms employed, will undoubtedly lead to the development of future antiretroviral therapies that will have the potential to block HIV-1 viral DNA integration. PMID- 22082287 TI - Challenges in implementing HIV laboratory monitoring in resource-constrained settings: how to do more with less. AB - Laboratory monitoring for HIV disease in resource-limited settings has now become one of the key challenges for antiretroviral treatment (ART) access and success, as emphasized by the 2010 revised WHO guidelines for ART in resource-limited settings. Thus, the most common method for initiating ART, and monitoring treatment response in resource-constrained environments is the measurement of CD4 T-cell count. Affordable CD4 T-cell counting has gradually been made possible by using simple, compact and robust, low-cost, new-generation cytometers, operating as single-platform volumetric instruments. Several cost-effective point-of-care CD4 T-cell testing options are also already on the market, in order to improve access to CD4 T-cell monitoring, especially for rural patients, and to reduce loss-to-follow-up of patients. In addition, HIV RNA viral load measurement is becoming increasingly important, mainly for a systematic confirmation of first line ART failure before switching to second-line treatment to avoid belated as well as premature therapeutic decisions and their potentially negative consequences. Viral load testing should now be considered as the standard of care for therapeutic failure in all resource-limited settings. However, the measurement of HIV viral load remains a centralized marker, carried out in a limited number of reference laboratories. Finally, the costs of second-line ART regimens, rather than the laboratory test costs themselves, currently constitute the primary determinant of the total cost in ART switching. Laboratory monitoring strategies may become more attractive as price negotiations render second-line ART regimens less expensive worldwide. PMID- 22082288 TI - The many roles of the highly interactive HSV protein ICP27, a key regulator of infection. AB - Human herpes viruses cause an array of illnesses ranging from cancers for Epstein?Barr virus and Kaposi?s sarcoma-associated herpes virus, to painful skin lesions, and more rarely, keratitis and encephalitis for HSV. All herpes viruses encode a multifunctional protein, typified by HSV ICP27, which plays essential roles in viral infection. ICP27 functions in all stages of mRNA biogenesis from transcription, RNA processing and export through to translation. ICP27 has also been implicated in nuclear protein quality control, cell cycle control, activation of stress signaling pathways and prevention of apoptosis. ICP27 interacts with many proteins and it binds RNA. This article focuses on how ICP27 performs its many roles and highlights similarities with its homologs, which could be targets for antiviral intervention. PMID- 22082289 TI - Bacterial type I signal peptidases as antibiotic targets. AB - Despite an alarming increase in morbidity and mortality caused by multidrug resistant bacteria, the number of antibiotics available to efficiently combat them is dwindling. Consequently, there is a pressing need for new drugs, preferably with novel modes of action to avert the problem of cross-resistance. Several new targets have been proposed, including proteins essential in the protein secretion pathway such as the type I signal peptidase (SPase), indispensable for the release of the signal peptide during secretion of Sec- and Tat-dependent proteins. The type I SPase is considered to be an attractive target because it is essential, substantially different from the eukaryotic counterpart, and its active site is located at the outer leaflet of the cytoplasmic membrane, permitting relatively easy access to potential inhibitors. A few SPase inhibitors have already been identified, but their suitability as drugs is yet to be confirmed. An overview is given on the currently known SPase inhibitors, how they can give valuable information on the structural, biochemical and target validation aspects of the SPases, the approaches to identify them, and their future potential as drugs. PMID- 22082291 TI - The twin-arginine translocation system: contributions to the pathobiology of Campylobacter jejuni. AB - The twin-arginine translocation (Tat) system is specialized in the transport of folded proteins across the cytoplasmic membrane. Although the mechanisms that govern the Tat transport and its scope are not well understood, this system and its cognate substrates are involved in important functions that facilitate the adaptation and survival of bacteria. Evidence also exists that connects the Tat system to virulent traits of clinically relevant pathogens. Of interest is Campylobacter jejuni, an important foodborne pathogen that is capable of surviving in different hosts and environmental niches. Recent studies have shown that the Tat system in this bacterium mediates key metabolic and stress resistance traits. Furthermore, the majority of the identified Tat substrates in C. jejuni are cofactor-containing redox proteins that contribute to the bacterium?s branched electron transport chain, a component essential for survival under differing conditions. These studies as well as the absence of Tat homologs in the sequenced genomes of animals suggest that the Tat system might pose an attractive target for therapeutics against C. jejuni. PMID- 22082290 TI - Genetics of Coxiella burnetii: on the path of specialization. AB - Coxiella burnetii is an extremely infectious, zoonotic agent that causes Q fever in humans. With the exception of New Zealand, the bacterium is distributed worldwide. Coxiella is classified as a select agent based on its past and potential use as a bioweapon and its threat to public health. Despite decades of research, we know relatively little regarding Coxiella?s molecular pathogenesis, and a vaccine is not widely available. This article briefly reviews the unusual genetics of C. burnetii; a pathogen that retains telltale genetic mementos collected over the course of its evolutionary path from a free-living bacterium to an obligate intracellular parasite of eukaryotic host cell phagosomes. Understanding why these genetic elements are maintained may help us better understand the biology of this fascinating pathogen. PMID- 22082292 TI - Scenery of Staphylococcus implant infections in orthopedics. AB - Infection is still the major complication of orthopedic implants and projections based on the actual trend indicate that total hip and knee arthroplasties and their consequent infection burden are destined to greatly increase. Staphylococcus aureus and Staphylococcus epidermidis are the leading etiologic agents of orthopedic implant infection. Here we report on epidemiology of implant related Staphylococcus infections in orthopedics, also referring to our experience, and focus on the crucial role of bacterial adhesins and on their ability to direct the pathogenesis process. Bacteria initiate implant infection by adhering to biomaterials. In the early steps of infection, adhesins mediate the specific interaction between microbial cells and the extracellular matrix proteins filming biomaterial surface. Then adhesin-mediated anchorage allows bacteria to cling to the biomaterial surface and to produce a biofilm that favors their ability to resist antibiotics. With the aim to prevent implant-related infections, anti-infective and infection-resistant biomaterials are being developed. The research for novel therapeutic strategies is incited by the emergence of antibiotic-resistant bacteria. Vaccines against the adhesins or antisense molecules against virulence genes can open a future in combating implant infections. PMID- 22082296 TI - Proton transfer from 2-naphthol to aliphatic amines in supercritical CO2. AB - The proton transfer from 2-naphthol to aliphatic amines was studied in supercritical CO(2) (scCO(2)) and in cyclohexane as reference solvent, by absorption and fluorescence spectroscopy and by time-resolved emission. Irradiation of 2-naphthol in scCO(2) in the presence of ethyldiisopropylamine shows dynamic fluorescence quenching of the acidic form of 2-naphthol and emission from the basic form. Fluorescence excitation spectra show that the emission of the basic form is originated upon excitation of the acidic form. The interaction between 2-naphthol and the amines is described by the formation of a complex with proton donor-acceptor character in the ground and excited states of 2-naphthol. The acidity increase of 2-naphthol upon electronic excitation to the first excited singlet in scCO(2) is as high as in water. Proton transfer quantum yields of 0.6 can be easily achieved in scCO(2). The results have implications for carrying out acid-base catalyzed reactions in scCO(2). PMID- 22082294 TI - Vesicular transport systems in fungi. AB - Canonical and unconventional mechanisms of secretion in many eukaryotic cells are relatively well known. In contrast to the situation in animal cells, mechanisms of secretion in fungi must include the capacity for trans-cell wall passage of macromolecules to the extracellular space. Although these mechanisms remain somewhat elusive, several studies in recent years have suggested that vesicular transport is required for trans-cell wall secretion of large molecules. Several fungal molecules, including proteins, lipids, polysaccharides and pigments, are released to the extracellular space in vesicles. In pathogenic fungi, a number of these vesicular components are associated with fungal virulence. Indeed, extracellular vesicles produced by fungi can interfere with the immunomodulatory activity of host cells. Fungal vesicles share many functional aspects with mammalian exosomes and extracellular vesicles produced by bacteria, plants and protozoa, but their cellular origin remains unknown. Here, we discuss the involvement of vesicular transport systems in fungal physiology and pathogenesis, making parallels with the mammalian, bacterial, protozoan and plant cell literature. PMID- 22082297 TI - Injury of fornix in patients with intracerebral hemorrhage. AB - OBJECTIVES: Many diffusion tensor tractography (DTT) studies have reported on fornix injury in various diseases. However, there has been no DTT study on fornix injury by intracerebral hemorrhage (ICH). We attempted to investigate fornix body injury in patients with ICH, using DTT. METHODS: We identified 58 consecutive stroke patients using the following criteria: (1) first-ever stroke, (2) age: 45 65 years, (3) hemorrhage confined within the corona radiata and basal ganglion level, (4) an available DTT scan performed during the early stage of ICH (1-5 weeks after onset). Among 58 consecutive patients, we identified six patients who showed disruption at the fornix body. RESULTS: Following ICH, 10.7% of patients revealed complete disruption of the fornix body on DTT. Results from DTT of the fornix showed disruption in anterior and posterior portions of the fornix body in three patients, in the anterior portion of the fornix body in two patient, and in the posterior portion of the fornix body in one patient. CONCLUSIONS: We report on six patients who showed complete disruption of the fornix body following ICH. It is our belief that the fornix of patients with ICH could be evaluated using DTT. PMID- 22082293 TI - Gametocytogenesis in malaria parasite: commitment, development and regulation. AB - Malaria parasites have evolved a complicated life cycle alternating between two hosts. Gametocytes are produced in the vertebrate hosts and are obligatory for natural transmission of the parasites through mosquito vectors. The mechanism of sexual development in Plasmodium has been the focus of extensive studies. In the postgenomic era, the advent of genome-wide analytical tools and genetic manipulation technology has enabled rapid advancement of our knowledge in this area. Patterns of gene expression during sexual development, molecular distinction of the two sexes, and mechanisms underlying subsequent formation of gametes and their fertilization have been progressively elucidated. However, the triggers and mechanism of sexual development remain largely unknown. This article provides an update of our understanding of the molecular and cellular events associated with the decision for commitment to sexual development and regulation of gene expression during gametocytogenesis. Insights into the molecular mechanisms of gametocyte development are essential for designing proper control strategies for interruption of malaria transmission and ultimate elimination. PMID- 22082298 TI - The risk of cryptorchidism among sons of women working in horticulture in Denmark: a cohort study. AB - BACKGROUND: Androgens are crucial for normal testicular descent. Studies show that some pesticides have estrogenic or antiandrogenic effects, and that female workers exposed to pesticides have increased risk of having a boy with cryptorchidism. The main objective of the present study was to investigate whether pregnant women exposed to pesticides due to their work in horticulture experience excess risk of having sons with cryptorchidism. METHODS: We conducted a cohort study of pregnant women working in horticulture using four cohorts including one cohort established with data from the departments of occupational medicine in Jutland and Funen and three existing mother-child cohorts (n=1,468). A reference group was established from the entire Danish population of boys born in the period of 1986-2007 (n=783,817). Nationwide Danish health registers provided information on birth outcome, cryptorchidism diagnosis and orchiopexy. The level of occupational exposure to pesticides was assessed by expert judgment blinded towards outcome status. Risk of cryptorchidism among exposed horticulture workers compared to the background population and to unexposed horticulture workers was assessed by Cox regression models. RESULTS: Pesticide exposed women employed in horticulture had a hazard ratio (HR) of having cryptorchid sons of 1.39 (95% CI 0.84; 2.31) and a HR of orchiopexy of 1.34 (0.72; 2.49) compared to the background population. Analysis divided into separate cohorts revealed a significantly increased risk of cryptorchidism in cohort 2: HR 2.58 (1.07;6.20) and increased risk of orchiopexy in cohort 4: HR 2.76 (1.03;7.35), but no significant associations in the other cohorts. Compared to unexposed women working in horticulture, pesticide exposed women had a risk of having sons with cryptorchidism of 1.34 (0.30; 5.96) and of orchiopexy of 1.93 (0.24;15.4). CONCLUSIONS: The data are compatible with a slightly increased risk of cryptorchidism in sons of women exposed to pesticides by working in horticulture. PMID- 22082299 TI - Clear cell meningioma with histologically aggressive appearance and clinically aggressive behavior: a case report. AB - Clear cell meningioma (CCM) is an uncommon variant of meningioma, corresponding to WHO grade II. We present a case of CCM with histologically aggressive appearance and clinically aggressive behavior. The tumor demonstrated rapid regrowth and brain metastasis. The histological progression from the ordinal CCM to the atypical area and higher MIB-1 index was observed. We assume that the short time of recurrence and metastasis may result from atypical histological features in our case. If the CCM has a histologically aggressive appearance as in our case, we suggest that postoperative adjuvant radiotherapy should be performed despite total resection of the tumor. PMID- 22082300 TI - Worthless donations: male deception and female counter play in a nuptial gift giving spider. AB - BACKGROUND: In nuptial gift-giving species, benefits of acquiring a mate may select for male deception by donation of worthless gifts. We investigated the effect of worthless gifts on mating success in the spider Pisaura mirabilis. Males usually offer an insect prey wrapped in silk; however, worthless gifts containing inedible items are reported. We tested male mating success in the following experimental groups: protein enriched fly gift (PG), regular fly gift (FG), worthless gift (WG), or no gift (NG). RESULTS: Males that offered worthless gifts acquired similar mating success as males offering nutritional gifts, while males with no gift experienced reduced mating success. The results suggest that strong selection on the nuptial gift-giving trait facilitates male deception by donation of worthless gifts. Females terminated matings faster when males offered worthless donations; this demonstrate a cost of deception for the males as shorter matings lead to reduced sperm transfer and thus give the deceiving males a disadvantage in sperm competition. CONCLUSION: We propose that the gift wrapping trait allows males to exploit female foraging preference by disguising the gift content thus deceiving females into mating without acquiring direct benefits. Female preference for a genuine prey gift combined with control over mating duration, however, counteracts the male deception. PMID- 22082301 TI - The effect of an intervention combining self-efficacy theory and pedometers on promoting physical activity among adolescents. AB - AIM: To study the effect of an intervention combining self-efficacy theory and pedometers on promoting physical activity among adolescents. BACKGROUND: The beneficial effects of regular physical activity on health in youths are well documented. However, adolescence is found to be the age of greatest decline in physical activity participation. Physical activity participation among girls was generally less frequent and less intense than boys. Therefore, there is a strong need for effective interventions that can help promote physical activity in this population. DESIGN: An experimental design. METHODS: Two classes of female junior college students (mean age = 16) were randomly sampled from a total of four classes and, of those, one each was randomly assigned to either the intervention (n = 46) or the control group (n = 48). Self-efficacy was used as a core theoretical foundation of the intervention design, and pedometers were provided to the students in the intervention group. Distances between each domestic scenic spot were illustrated graphically in a walking log for students to mark the extent of their walking or running. Students in the control group participated in a usual physical education programme. The primary outcome was a change in the number of aerobic steps. The secondary outcomes were changes in cardiopulmonary endurance and exercise self-efficacy. RESULTS: At 12-week follow-up, the mean change in aerobic steps was 371 steps and 108 steps in the intervention and control group, respectively. The difference in mean change between the two groups was 467 steps. Effects of the intervention on changes of cardiopulmonary endurance and perceived exercise self-efficacy scores were not found. CONCLUSIONS: Among adolescent girls, a 12-week intervention designed on the theoretical foundation of self-efficacy theory and provision of pedometers was found to have an effect on increasing their physical activity. The intervention, using graphs of domestic scenic spots to represent the distance of walking or running as monitored by pedometers, might enhance motivation regarding physical activity. RELEVANCE TO CLINICAL PRACTICE: It is important for health professionals, including school health nurses, involved in the care of adolescent health, to design and provide a physical activity intervention combining self efficacy theory and provision of pedometer to promote physical activity. PMID- 22082302 TI - Isolated distal deep vein thrombosis: what we know and what we are doing. AB - Thromboses that are restricted to the infra-popliteal deep veins of the lower limbs (isolated distal deep vein thrombosis, IDDVT) are frequently diagnosed in subjects with suspected pulmonary embolism (PE; 7-10%) or DVT(4-15%), accounting for 31-56% of all diagnosed leg DVTs. Despite their frequency, IDDVTs still remain one of the most debated issues in the field of venous thromboembolism (VTE). Conflicting clinical results have resulted in differing opinions on the need to test for IDDVTs and how to treat them. Due to discordant results, the real risk of IDDVT-associated PE is not well established. IDDVTs are associated with (i) lower risk of recurrence when compared with other VTEs, and (ii) fewer late sequelae than proximal DVT. Diagnosis of IDDVT is based on ultrasound examination of all calf veins, which is more operator-dependent and less sensitive than proximal vein examination. A series of studies has shown, however, that a single complete ultrasound strategy in symptomatic patients has comparable clinical results to serial proximal ultrasound, allowing approximately 15% better DVT diagnosis. Optimal treatment of IDDVT is still controversial. Guidelines recommend anticoagulation for 12 weeks, although 6 weeks may be sufficient. There is, however, insufficient data to support the diagnosis and treatment of all IDDVTs, and the necessary criteria to identify subjects at higher risk of complication are lacking. It also seems likely that different approaches may be better for unprovoked or secondary events and for deep or muscle veins. Specifically designed and adequately powered clinical studies addressing the issue of IDDVT need to be urgently undertaken. PMID- 22082303 TI - Alkalinized lidocaine and heparin provide immediate relief of pain and urgency in patients with interstitial cystitis. AB - INTRODUCTION: It has been reported in an open-label study that the combination of alkalinized lidocaine and heparin can immediately relieve the symptoms of urinary urgency, frequency, and pain associated with interstitial cystitis (IC). This combination has also been reported to relieve pain associated with sex in patients with IC. AIM: The aim of this study was to corroborate these findings in a multicenter setting. METHODS: The study design was a multicenter prospective, double-blind, crossover, placebo-controlled trial. Each participant met all of the clinical National Institute of Diabetes and Digestive and Kidney Diseases criteria (excluding cystoscopy) for IC. Each patient received drug and control, in random order, within 48 hours of enrolling in the study. MAIN OUTCOME MEASURES: The primary outcome measure was percent change in pain score (11-point analog pain scale) 12 hours after receiving the drug or control. Secondary measures were the global assessment response (GAR) of symptoms and 12-hour average urgency reduction determined from 11-point urgency scales. RESULTS: Eighteen (18) patients completed the trial. The average reduction of pain over 12 hours was 21% for control and 42% for active drug (P = 0.0363). GAR was 13% for control and 50% for drug (P = 0.0137). Average urgency reduction was 13% for control and 35% for drug (P = 0.0328). CONCLUSIONS: The combination of alkalinized lidocaine and heparin provides up to 12 hours of relief from urgency and pain associated with IC. This combination provides significant immediate relief of symptoms for patients with IC. PMID- 22082304 TI - Binder phenotype in mothers affected with autoimmune disorders. AB - OBJECTIVE: To report four foetal cases of the Binder phenotype associated with maternal autoimmune disorders. PATIENTS AND METHODS: In three mothers with autoimmune diseases, 2D and 3D ultrasonographic measurements were made on four foetuses with the Binder profile, and were compared with postnatal phenotypes. RESULTS: The Binder phenotype can be detected in early pregnancy (14.5 WG). All foetuses had verticalized nasal bones and midfacial hypoplasia. Punctuate calcifications were found in almost all the cases. No specific maternal auto antibody has been associated with foetal Binder phenotype. CONCLUSION: Since the Binder phenotype can be diagnosed at ultrasound examination during pregnancy, it is important to establish the underlying cause so as to assess the foetal prognosis. This study stresses the importance of systematic checks for maternal autoimmune disease in cases of prenatally diagnosed Binder phenotypes. PMID- 22082305 TI - Azobenzene photoswitching without ultraviolet light. AB - Most azobenzene-based photoswitches use UV light for photoisomerization. This can limit their application in biological systems, where UV light can trigger unwanted responses, including cellular apoptosis. We have found that substitution of all four ortho positions with methoxy groups in an amidoazobenzene derivative leads to a substantial (~35 nm) red shift of the n-pi* band of the trans isomer, separating it from the cis n-pi* transition. This red shift makes trans-to-cis photoswitching possible using green light (530-560 nm). The cis state is thermally stable with a half-life of ~2.4 days in the dark in aqueous solution. Reverse (cis-to-trans) photoswitching can be accomplished with blue light (460 nm), so bidirectional photoswitching between thermally stable isomers is possible without using UV light at all. PMID- 22082306 TI - Phenomenological shifts for healthcare professionals after experiencing a research-based drama on living with dementia. AB - AIM: The aim of this article is to report research findings describing phenomenological shifts, that is, changes in patterns of lived experience, for healthcare professionals who attended a performance of a research-based drama, called I'm Still Here. BACKGROUND: The research drama, based on six studies, was created to help change the ways persons understand, think about and relate with persons living with dementia. METHODS: In 2006-2007, 50 healthcare professionals from various disciplines and eight nursing students participated in this study. Participants were recruited from four Canadian cities in the province of Ontario where focus groups were held before and after engaging in a live performance of I'm Still Here. FINDINGS: Analysis of focus group transcripts showed shifts in patterns of lived experience for the healthcare professional participants as evident in the participants' descriptions. The phenomenological shifts reflected a move from descriptions of 'diminishing humanness to discerning humanness', from 'disengaged care/mundane relating to reflexive relating in the now', and 'terrifying portrayals of loss to awakening to hopeful possibility'. The shifts described herein are supported with examples from the focus group transcripts. CONCLUSIONS: Findings reveal the power of drama as a vibrant and meaningful means of shifting understandings, images and intended actions of healthcare professions which have the potential to affect the lived experiences, relationships and quality of life of persons with dementia. PMID- 22082307 TI - Nanoparticle mediated targeting of VEGFR and cancer stem cells for cancer therapy. AB - Angiogenesis is a crucial process in tumor pathogenesis as it sustains malignant cells with nutrients and oxygen. It is well known that tumor cells secrete various growth factors, including VEGF, which triggers endothelial cells to form new capillaries. Prevention of expansion of new blood vessel networks results in reduced tumor size and metastasis. Production of VEGF is driven by hypoxia via transcriptional activation of the VEGF gene by HIF-1alpha.Tumours are now understood to contain different types of cells, and it is the cancer stem cells that retain the ability to drive the tumour's growth. They are called cancer stem cells because, like stem cells present in normal tissues of the body, they can self-renew and differentiate. These cancer stem cells are responsible for the relapse of cancer as they are found to be resistant to conventional modes of cancer therapy like chemotherapy and radiation.In this review, a novel mode of treatment of cancer is proposed, which utilizes the twin nanoparticle to target endothelial cells in the niche of cancer stem cell. The nanoparticle discussed in this review, is a twin nanoparticle of iron coated with gold, which targets VEGF positive cell in the vicinity of cancer stem cell. In the twin nanoparticle, one particle will recognize cancer stem cell, and another conjugated nanoparticle will recognize VEGF positive cells, thereby inhibiting endothelial cells in the proximity of cancer stem cell. This novel strategy will inhibit angiogenesis near cancer stem cell hence new tumour cannot grow and old tumour will be unable to metastasize. PMID- 22082308 TI - The expression and clinical significance of pSTAT3, VEGF and VEGF-C in pancreatic adenocarcinoma. AB - Signal transducers and activators of transcription 3 (STAT3) is a central cytoplasmic transcription factor and regulates a number of pathways important in tumorigenesis including cell cycle progression, apoptosis, tumor angiogenesis, invasion and metastasis.This study aims to investigate the expression of pSTAT3, VEGF and VEGF-C in pancreatic adenocarcinoma and their relations to the clinicopathological features, tumor angiogenesis and prognosis. In the present study, the expression of pSTAT3, VEGF and VEGF-C and microvascular density (MVD) were examined via immunohistochemistry. The clinicopathological information was collected and patients were regularly followed up. The relationship between the parameters and the clinicopathological features were analyzed, and the univariate and multivariate prognostic factors were also analyzed. The expression of pSTAT3 in tumor tissues was significantly higher in contrast to that in normal tissues, and pSTAT3 was related to VEGF and VEGF-C expression, MVD, tumor size, lymphogenous status and TNM staging (P<0.05). Survival analysis suggested that tumor size, TNM staging, pSTAT3 and VEGF expression were risk factors of prognosis, but no independent factors were found. We concluded that pSTAT3, which was a risk factor of prognosis, was abnormally expressed in pancreatic adenocarcinoma and related to tumor size, TNM staging and lymphatic metastasis. pSTAT3 may promote tumor angiogenesis via up-regulating VEGF on protein and even gene levels, and enhance the early lymphatic metastasis through VEGF-C. Better understanding of STAT3 signaling pathways in angiogenesis may contribute to the development of novel therapeutic strategies in angiogenesis and metastasis of pancreatic cancer. PMID- 22082309 TI - The influence of neuropilin-1 silencing on semaphorin 3A and 3C activity in B16(F10) murine melanoma cells. AB - Neuropilin-1 (Nrp1), originally characterized as an adhesion molecule in the nervous system, is a co-receptor for class-3 semaphorins. Neuropilins and semaphorins are highly expressed in a wide spectrum of tumors and have been shown to influence their growth and vascularization. Despite the growing body of data on neuropilin/semaphorin regulation of tumor growth, still the exact mechanism of their activity remains to be elucidated. Previously published data suggests that Nrp1 has both anti- and promigratory characteristics in different tumor types, although no data is available on its role in melanoma cells. In this paper, we studied the effect of Nrp1 downregulation on B16(F10) melanoma cells migration. Our results show that the silencing of Nrp1 significantly increases the overall mobility of B16(F10) cells and changes their morphology. Moreover, Nrp1-silenced B16(F10) cells show a decreased response to Sema3A. We also observed reduced binding of Sema3A to these cells. Contrarily, no changes were observed in the binding of Sema3C to Nrp1-silenced B16(F10) cells, nor in its chemorepellent activity. Our results suggest that modulation of B16(F10) cells migratory ability by semaphorin 3A can be preferentially mediated by Nrp1, while the contribution of semaphorin 3C in this process is less evident. In addition, silencing of Nrp1 did not change the migratory ability of B16(F10) cells towards VEGF. PMID- 22082310 TI - Repeated mitral valve replacement in a patient with extensive annular calcification. AB - BACKGROUND: Mitral valve replacement in the presence of severe annular calcification is a technical challenge. CASE REPORT: A 47-year-old lady who had undergone mitral and aortic valve replacement for rheumatic disease 27 years before presented with dyspnea. At reoperation, extensive mitral annular calcification was hindering the disc motion of the Starr-Edwards mitral prosthesis. The old prosthesis was removed and a St Jude Medical mechanical valve was implanted after thorough annular debridement. Postoperatively the patient developed paravalvular leak and hemolytic anemia, subsequently undergoing reoperation three days later. The mitral valve was replaced with an Edwards MIRA valve, with a bulkier sewing cuff, after more aggressive annular debridement. Although initially there was no paravalvular leak, it recurred five days later. The patient also developed a small cerebral hemorrhage. As the paravalvular leak and hemolytic anemia gradually worsened, the patient underwent reoperation 14 days later. A Carpentier-Edwards bioprosthetic valve with equine pericardial patches, one to cover the debrided calcified annulus, another as a collar around the prosthesis, was used to eliminate paravalvular leak. At 7 years postoperatively the patient is doing well without any evidence of paravalvular leak or structural valve deterioration. CONCLUSION: Mitral valve replacement using a bioprosthesis with equine pericardial patches was useful to overcome recurrent paravalvular leak due to severe mitral annular calcification. PMID- 22082311 TI - Strawberries, blueberries, and cranberries in the metabolic syndrome: clinical perspectives. AB - Emerging science supports therapeutic roles of strawberries, blueberries, and cranberries in metabolic syndrome, a prediabetic state characterized by several cardiovascular risk factors. Interventional studies reported by our group and others have demonstrated the following effects: strawberries lowering total and LDL-cholesterol, but not triglycerides, and decreasing surrogate biomarkers of atherosclerosis (malondialdehyde and adhesion molecules); blueberries lowering systolic and diastolic blood pressure and lipid oxidation and improving insulin resistance; and low-calorie cranberry juice selectively decreasing biomarkers of lipid oxidation (oxidized LDL) and inflammation (adhesion molecules) in metabolic syndrome. Mechanistic studies further explain these observations as up-regulation of endothelial nitric oxide synthase activity, reduction in renal oxidative damage, and inhibition of the activity of carbohydrate digestive enzymes or angiotensin-converting enzyme by these berries. These findings need confirmation in future studies with a focus on the effects of strawberry, blueberry, or cranberry intervention in clinical biomarkers and molecular mechanisms underlying the metabolic syndrome. PMID- 22082312 TI - Intraprocedural and long-term incomplete occlusion of the left atrial appendage following placement of the WATCHMAN device: a single center experience. AB - INTRODUCTION: Transcatheter left atrial appendage (LAA) closure with the WATCHMAN device has become one of the therapeutic options in atrial fibrillation (AF) patients who are at high risk for ischemic stroke. However, the incidence and evolution of incomplete occlusion of the LAA during and after placement of the WATCHMAN device has not been reported. METHODS AND RESULTS: Fifty-eight consecutive patients who had undergone WATCHMAN device implant were included in the study. Intraprocedural, 45-day and 12-month transesophageal echocardiogram images were reviewed and analyzed. Peridevice gap was noted in 16 (27.6%), 17 (29.3%), and 20 (34.5%) patients across the 3 time points. Intraprocedural gaps are more likely to be persistent until 12 months and become larger in size over time. New gap also occurs during follow-up even if the LAA was completely sealed at implantation. One patient had an ischemic stroke 4.7 months after implant; another patient developed a left atrial thrombus over the device 21.6 months after implant. Both patients had intraprocedural gap and discontinued warfarin therapy after the 45-day evaluation. CONCLUSION: Incomplete LAA occlusion with a gap between the WATCHMAN device surface and the LAA wall is relatively common. Intraprocedural gaps are more likely to become bigger over time and persist, while new gaps also occur during follow-up. Further studies are warranted to verify whether the presence and persistence of a peridevice gap is associated with increased risk of thromboembolic event in AF patients implanted with a WATCHMAN device. PMID- 22082313 TI - Platelet transfusion alters CD40L blood level and release capacity in patients suffering from thrombocytopenia. AB - BACKGROUND: Platelet (PLT)-derived cytokines, such as soluble CD40 ligand (sCD40L), play an important role in the development of adverse transfusion reactions associated with the administration of PLT products. In this study, we determined sCD40L concentration and release capacity in patients with thrombocytopenia before and after receiving a PLT transfusion. STUDY DESIGN AND METHODS: The study included 12 patients suffering from chemotherapy-induced thrombocytopenia. sCD40L levels and release capacity were measured in plasma samples of the patients before and after PLT administration as well as in the respective plateletpheresis concentrates by enzyme-linked immunosorbent assay. Sixteen healthy blood donors served as a control group. RESULTS: In PLT concentrates, elevated sCD40L levels (2567+/-134 pg/mL) were observed in comparison to plasma sCD40L levels in controls (238.4+/-35.3 pg/mL). sCD40L plasma concentration of patients with thrombocytopenia was significantly reduced (86.3+/-16.7 pg/mL) before transfusion and increased to nearly normal levels (204.4+/-24.8 pg/mL) after PLT administration. In parallel, the sCD40L release capacity per PLT showed no significant difference between controls and patients with thrombocytopenia before transfusion (33.3+/-2.6 and 29.3+/-4.6 ag/PLT, respectively) but was significantly reduced after PLT transfusion (22.4+/-2.7 compared to 29.3+/-4.6 ag/PLT). CONCLUSIONS: In patients with thrombocytopenia, sCD40L levels were clearly influenced by PLT transfusions: PLT administration led to a normalization of sCD40L plasma concentration. Nevertheless, adverse transfusion reactions did not occur in these patients. The sCD40L release capacity was enhanced by PLT administration dependent on the increase in the amount of PLT count. PMID- 22082314 TI - Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107). AB - The mammalian target of rapamycin (mTOR) signalling pathway has emerged as an important therapeutic target for acute myeloid leukaemia (AML). This study assessed the combination of temsirolimus, an mTOR inhibitor, and lower-dose clofarabine as salvage therapy in older patients with AML. Induction consisted of clofarabine 20mg/m(2) on days 1-5 and temsirolimus 25mg (flat dose) on days 1, 8 and 15. Patients achieving complete remission with (CR) or without (CRi) full haematological recovery could receive monthly temsirolimus maintenance. In 53 evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). Median disease-free survival was 3.5months, and median overall survival was 4months (9.1months for responders). The most common non-haematological severe adverse events included infection (48%), febrile neutropenia (34%) and transaminitis (11%). The 30-d all-cause induction mortality was 13%. Laboratory data from 25 patients demonstrated that a >50%in vivo inhibition of S6 ribosomal protein phosphorylation was highly correlated with response rate (75% with inhibition versus 0% without inhibition; P=0.0001), suggesting that targeting the mTOR pathway is clinically relevant. The acceptable safety profile and the predictive value of target inhibition encourage further investigation of this novel regimen. PMID- 22082315 TI - Microinjection of HSV-1 amplicon vector-mediated human proenkephalin into the periaqueductal grey attenuates neuropathic pain in rats. AB - We investigated the antinociceptive effect of microinjection of HSV-1 amplicon vector-mediated human proenkephalin (hPPE) into the ventral periaqueductal grey (PAG) on neuropathic pain in rats. Male Sprague-Dawley rats with chronic constriction injury (CCI)-induced neuropathic pain were microinjected into the ventral PAG with normal saline (NS), pHSVIRES-lacZ (SHZ), or HSV-1 amplicon vector pHSVIRES-hPPE-lacZ (SHPZ), respectively. Pain thresholds in the SHPZ treated rats were significantly higher at day 3, then reached peak at day 14 and lasted until day 35 after PAG administration, and these effects were reversed by naloxone. In contrast, NS or SHZ-treated rats did not significantly affect pain thresholds. These results demonstrated that microinjection of HSV-1 amplicon vector-mediated hPPE into the ventral PAG attenuates neuropathic pain in rats. PMID- 22082317 TI - Synthesis of the asperparaline core by a radical cascade. AB - A concise access to the pentacyclic core structure of the asperparalines is described. The key step is a radical cascade sequence comprised of a 1,6-hydrogen atom transfer followed by 6-exo-trig and 5-exo-trig cyclizations. PMID- 22082316 TI - Automated time activity classification based on global positioning system (GPS) tracking data. AB - BACKGROUND: Air pollution epidemiological studies are increasingly using global positioning system (GPS) to collect time-location data because they offer continuous tracking, high temporal resolution, and minimum reporting burden for participants. However, substantial uncertainties in the processing and classifying of raw GPS data create challenges for reliably characterizing time activity patterns. We developed and evaluated models to classify people's major time activity patterns from continuous GPS tracking data. METHODS: We developed and evaluated two automated models to classify major time activity patterns (i.e., indoor, outdoor static, outdoor walking, and in-vehicle travel) based on GPS time activity data collected under free living conditions for 47 participants (N = 131 person-days) from the Harbor Communities Time Location Study (HCTLS) in 2008 and supplemental GPS data collected from three UC-Irvine research staff (N = 21 person-days) in 2010. Time activity patterns used for model development were manually classified by research staff using information from participant GPS recordings, activity logs, and follow-up interviews. We evaluated two models: (a) a rule-based model that developed user-defined rules based on time, speed, and spatial location, and (b) a random forest decision tree model. RESULTS: Indoor, outdoor static, outdoor walking and in-vehicle travel activities accounted for 82.7%, 6.1%, 3.2% and 7.2% of manually-classified time activities in the HCTLS dataset, respectively. The rule-based model classified indoor and in-vehicle travel periods reasonably well (Indoor: sensitivity > 91%, specificity > 80%, and precision > 96%; in-vehicle travel: sensitivity > 71%, specificity > 99%, and precision > 88%), but the performance was moderate for outdoor static and outdoor walking predictions. No striking differences in performance were observed between the rule-based and the random forest models. The random forest model was fast and easy to execute, but was likely less robust than the rule-based model under the condition of biased or poor quality training data. CONCLUSIONS: Our models can successfully identify indoor and in-vehicle travel points from the raw GPS data, but challenges remain in developing models to distinguish outdoor static points and walking. Accurate training data are essential in developing reliable models in classifying time-activity patterns. PMID- 22082318 TI - Phosphorylated alpha-synuclein immunoreactivity in the posterior pituitary lobe. AB - Parkinson's disease is now recognized as a major form of alpha-synucleinopathy involving both the central and peripheral nervous systems. However, no research has focused on the posterior pituitary lobe (PPL), despite the fact that this organ also plays an important role in systemic homeostasis. In the present study, we aimed to distinguish phosphorylated alpha-synuclein (palphaSyn)-positive deposits in the PPL, as is observed in Lewy body- and non-Lewy body-related disorders. PalphaSyn deposits were immunohistochemically analyzed using formalin fixed, paraffin-embedded PPL specimens obtained from 60 autopsy cases. Among the cases with Lewy body-related disorders, PPL palphaSyn deposits were observed in almost all cases of Parkinson's disease (22/23), and in one case of dementia with Lewy bodies (1/1). On the other hand, only 3/36 cases of non-Lewy body-related disorders had palphaSyn immunoreactivity in the PPL. The present study confirms the presence of palphaSyn-positive deposits, as demonstrated by high specificity (97.1%) and sensitivity (88.5%), in both Parkinson's disease and dementia with Lewy bodies, suggesting that this finding can be a useful hallmark of Lewy body related disorders. PMID- 22082319 TI - Control of 1,3-cyclohexadiene photoisomerization using light-induced conical intersections. AB - We have studied the photoinduced isomerization from 1,3-cyclohexadiene to 1,3,5 hexatriene in the presence of an intense ultrafast laser pulse. We find that the laser field maximally suppresses isomerization if it is both polarized parallel to the excitation dipole and present 50 fs after the initial photoabsorption, at the time when the system is expected to be in the vicinity of a conical intersection that mediates this structural transition. A modified ab initio multiple spawning (AIMS) method shows that the laser induces a resonant coupling between the excited state and the ground state, i.e., a light-induced conical intersection. The theory accounts for the timing and direction of the effect. PMID- 22082320 TI - To lube or not to lube: experiences and perceptions of lubricant use in women with and without dyspareunia. AB - INTRODUCTION: There are few studies examining the relationship between lubricant use and sexual functioning, and no studies have examined this relationship in women with dyspareunia. Vaginal dryness is a prevalent complaint among women of all ages. There is an association between vaginal dryness and painful intercourse; therefore, women with dyspareunia represent a particularly relevant sample of women in which to investigate lubricant use. AIM: The aim of this study was to examine differences between women with and without dyspareunia in self reported natural lubrication and attitudes toward and use of personal lubricants. METHODS: Respondents completed an online survey including questions on demographics, gynecological/medical history, sexual functioning, and lubricant use and attitudes. MAIN OUTCOME MEASURES: The main outcome measures used were the Female Sexual Function Index (FSFI) and questions regarding attitudes toward and use of lubricants. RESULTS: Controls scored higher on the lubrication subscale of the FSFI than women with dyspareunia (P < 0.001). Women with dyspareunia reported greater frequency of lubricant use during sexual activity over the last year (P < 0.01). They were also more likely to use lubricant prior to penetration (P < 0.05). The most common use for controls was to enhance sexual experiences. This was also a common answer for women with dyspareunia; however, in this group, the most common reason was to reduce/alleviate pain. Lubricants were rated as less effective among women with dyspareunia vs. controls across all reported reasons for use. Nevertheless, lubricant use was still rated as being moderately effective in alleviating pain for women with dyspareunia. CONCLUSIONS: Women with dyspareunia have more difficulty with natural lubrication; it is consequently not surprising that they reported using lubricant more frequently than control women. Women with dyspareunia reported using lubricants more often than controls to try to prevent or alleviate pain and reported this as being a moderately effective strategy, suggesting that it may be a useful tool for some women with dyspareunia. PMID- 22082321 TI - Predicting factors of pressure ulcers in older Thai stroke patients living in urban communities. AB - AIM AND OBJECTIVE: To describe the contributing factors for pressure ulcer development in older Thai stroke patients in an urban community. BACKGROUND: Pressure ulcers are a common problem signifying a source of morbidity and mortality in older stroke patients. In the past, most studies have focused on the physiological factors affecting pressure ulcer development. However, studies related to effect of stroke severity and psychosocial factors in community-based setting have not found. DESIGN: Cross-sectional survey design. METHODS: One hundred and sixty-eight older stroke patients from urban communities in three districts in metropolitan Thailand were recruited for this cross sectional study. Data were collected from the Skin Assessment Tool, the Braden scale, the Canadian Neurological Scale, the Social Support Questionnaire and the Thai Geriatric Depression Scale for each patient. The results were analysed using multiple logistic regression and the chi-square test. RESULTS: Eighty older stroke patients who developed pressure ulcers (47.6%). The participants were aged between 60-93 years. Multiple logistic regression analysis was applied to calculate the odds ratio. The significant predicting factors for pressure ulcers were activity, moisture, nutrition, friction and shearing and depression. Sensory perception, mobility, severity of stroke and social support were not found to be significant predictors. CONCLUSIONS: Physiological factors and depression were found to be significant predicting factors for pressure ulcer development in older stroke patients living in an urban community. RELEVANCE TO CLINICAL PRACTICE: To help prevent pressure ulcers in older stroke patients, the findings suggest that healthcare providers assess activity, moisture, nutrition, friction and shearing, as well as psychological assessment for depression. The results indicate that models for pressure ulcer prevention merit further investigation. PMID- 22082322 TI - Anacetrapib: a new weapon against dyslipidemia. AB - Anacetrapib is a cholesteryl-ester-transfer-protein (CETP) inhibitor, a new class of experimental drugs in the treatment of primary hypercholesterolemia and dyslipidaemia associated with the metabolic syndrome. One of the major advantages of this agent is, apart from the significant decrease in LDL-C it produces a substantial increase in HDL-C. Phase I, II, and III clinical trials have shown that anacetrapib is safe alone or in combination with statins. However, longterm clinical trials are required in order to assess whether it reduces mortality in individuals at high-risk of cardiovascular disease. PMID- 22082323 TI - Olfactory dysfunction and cognitive impairment in age-related neurodegeneration: prevalence related to patient selection, diagnostic criteria and therapeutic treatment of aged clients receiving clinical neurology and community-based care. AB - A decrease in olfactory function with age has been attributed to a variety of factors including normal anatomical and physiological changes in aging, surgery, trauma, environmental factors, medications and disease. Olfactory impairment has also been associated with neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease. Deficits in these chemical senses cannot only reduce the pleasure and comfort from food, but represent risk factors for nutritional and immune deficiencies as well as adherence to specific dietary regimens. Therapy is limited, but one should be aware of the existing medical and surgical treatment modalities. Reactive oxygen and nitrogen species, copper and zinc ions, glycating agents and reactive aldehydes, protein cross-linking and proteolytic dysfunction may all contribute to neurodegeneration, olfactory dysfunction, AD. Carnosine (beta-alanyl- L-histidine) is a naturally-occurring, pluripotent, homeostatic transglycating agent. The olfactory lobe is normally enriched in carnosine and zinc. Loss of olfactory function and oxidative damage to olfactory tissue are early symptoms of AD. Protein and lipid oxidation and glycation are integral components of the AD pathophysiology. Carnosine can suppress amyloidbeta peptide toxicity, inhibit production of oxygen free radicals, scavenge hydroxyl radicals and reactive aldehydes, and suppresses protein glycation. The observations suggest that patented non-hydrolyzed carnosine lubricant drug delivery or perfume toilet water formulations combined with related moiety amino acid structures, such as beta-alanine, should be explored for therapeutic potential towards olfactory dysfunction, AD and other neurodegenerative disorders. "The olfactory system, anatomically, is right in the middle of the part of the brain that's very important for memory. There are strong neural connections between the two." ~ Donald Wilson. PMID- 22082325 TI - Unexpected high levels of vorinostat when combined with vinorelbine in patients with advanced cancer. AB - BACKGROUND: This study was a multi-centre, dose-escalation trial in patients with advanced cancers. Primary objective was to determine maximum tolerated dose (MTD) of vorinostat, a competitive inhibitor of histone deacetylase (HDAC), in combination with vinorelbine. Secondary aims were to determine (1) corresponding pharmacokinetics, (2) safety of this regimen, and (3) impact of UGT1A1 and 2B17 polymorphisms on vorinostat pharmacokinetics. METHODS: Starting dose of once daily oral vorinostat was 200 mg for 7 days every 21 days in combination with a 20-min intraveinous weekly infusion of vinorelbine 25 mg/m2, starting 4 hours after the first vorinostat dose. During cycle 1, blood samples were collected at day 1 for vorinostat and at days 1 and 8 for vinorelbine for pharmacokinetic evaluation. RESULTS: Seven patients were included. Most of adverse events observed were mild (grades 0-2) and reversible after treatment discontinuation (hemotological toxicity, asthenia, diarrhea, dyspnea, fever, hyperglycemia and nausea). Two patients had a dose limiting toxicity at the first dose level that consisted of grade 3 hyperglycemia and vinorelbine administration was delayed. The first dose-level was considered as the MDT and therefore dose escalation was stopped. Mean vorinostat plasma AUC was higher than reported previously at a similar dose when used as single agent or in combination with other cytotoxics. There was no obvious vinorelbine-vorinostat interaction nor any correlation with UGT1A1 or 2B17 polymorphisms. CONCLUSION: MDT of the combination was 200 mg oral vorinostat for 7 days in combination with 25 mg/m2 weekly vinorelbine. Severity of hyperglycemia was most likely related to unexpected high vorinostat exposures. PMID- 22082326 TI - Supplementation of glutamine and omega-3 polyunsaturated fatty acids as a novel therapeutic intervention targeting metabolic dysfunction and exercise intolerance in patients with heart failure. AB - With its increasing prevalence throughout the world, heart failure continues to be associated with high morbidity and mortality. Patients with heart failure develop progressive metabolic abnormalities, inflammation, and atrophy in the myocardium and skeletal muscle. Improvement in functional capacity as defined by exercise tolerance is essential for better quality of life and potentially survival of these patients. Therapeutic management options aimed at improving peripheral organ function are limited. Nutritional approaches with dietary supplementation in addition to current therapies are particularly appealing as they are novel and mechanistically different. In this article, we review the role of glutamine and omega-3 polyunsaturated fatty acids on metabolism and functional capacity in heart failure. These two compounds are of particular interest due to their synergistic role on oxidative metabolism, lipolysis and inflammation. PMID- 22082324 TI - Metabolic correction in the management of diabetic peripheral neuropathy: improving clinical results beyond symptom control. AB - Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyl-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metformin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk of developing DPN and how metabolic correction can reduce these risks. PMID- 22082327 TI - Drug-induced anemia and other red cell disorders: a guide in the age of polypharmacy. AB - Several medications have been linked to red blood cell (RBC) disorders. The frequency of these side effects varies, depending on the condition, but they can be associated with significant morbidity and mortality. The problem is likely to exacerbate in aging populations with frequent comorbidities, proportional to the growing number of medications used. Notable drug-related RBC disorders include hemolytic anemia, megaloblastic anemia, sideroblastic anemia, polycythemia, methemoglobinemia, anemia of irritation/inflammation, and anemia caused by suppression of RBC production. The list of medications that are associated with these disorders is long and includes many commonly-used drugs. This could pose a challenge in timely diagnosis and management of these disorders. Prior knowledge of the potential for drug-related RBC disorders and monitoring the patients who are being treated with medications known to cause RBC disorders are critical to ensure timely and effective response, should such adverse reactions occur. PMID- 22082328 TI - Antibiotic resistance of bacterial strains isolated from patients with community acquired urinary tract infections: an exploratory study in Palestine. AB - BACKGROUND AND OBJECTIVES: No studies about resistance of bacteria isolated from patients with community-acquired urinary tract infections (CA-UTI) or local guidelines for antibiotic use in these infections have been published or established in the West Bank, Palestine. The objectives of this study were to determine the (1) type and frequency of isolated bacteria and (2) their resistance to commonly used antibiotics. METHODS: A cross sectional study on community urinary isolates was carried out in Nablus, Palestine between November 2009 and April 2010. A convenience sampling method was used for collection of specimens. RESULTS: A total of 375 specimens were collected from 306 (81.6%) females and 69 (18.4%) males. Three hundred and thirty nine (90.4%) of isolated uropathogens were Gram-negative bacteria, of which 243 (71.7%) were Escherichia coli. Thirty six (9.6 %) of the total isolates were Gram-positive bacteria, of which 21 (58.3%) were Staphylococcus saprophyticus. High resistance rates were recorded for E. coli against trimethoprim/sulfamethoxazole (37%), nitrofurantoin (29%), ampicillin (65%), and nalidixic acid (37%). E. coli showed low resistance to amoxicillin/clavulanic acid, ciprofloxacin, cefotaxime and ceftriaxone with rates of 12.2, 17.2, 11.1, and 11.1% respectively. CONCLUSION: E. coli was the most frequent bacterium in the studied sample and showed high resistance to first line antibiotics. Our results highlight the need for developing local guidelines where elevated resistance to antibiotics should influence prescribing decisions. PMID- 22082329 TI - The clinical pharmacology of short acting analgo-sedatives in neonates. AB - Effective pain management remains an important indicator of the quality of care provided to neonates, not only from an ethical, but also from a clinical outcome perspective. Significant progresses in non-pharmacological therapies have been made. However - in the meanwhile - neonatal practice also evolved. These shifts in clinical care also induced in a shift in pharmacodynamic end points, and consequently, new pharmacological observations are needed with emphasis on short acting procedural analgo-sedatives. Analgo-sedation in neonates remains a balanced decision based on systematic assessment (pharmacodynamics, PD), followed by titrated administration of the most appropriate analgesic(s) (PK) with subsequent re-assessment (PD) to adapt and further titrate exposure and effects. In this review, we will focus on aspects of the clinical pharmacology (pharmacokinetics (PK) and -dynamics) of newly emerging, short acting analgo sedatives (midazolam, propofol, remifentanil, inhalational agents, ketamine) in neonates. Based on the currently available information on predictability of disposition and the limited pharmacodynamic side effects (hemodynamics, neuro apoptosis), it seems that remifentanil is the most promising compound for further evaluation. PMID- 22082331 TI - From laparoscopic assisted radical vaginal hysterectomy to vaginal assisted laparoscopic radical hysterectomy. AB - Radical hysterectomy with pelvic lymphadenectomy is the standard surgical treatment for patients with early stage cervical cancer. The majority of radical hysterectomies are performed with the open technique. However, laparoscopic, combined laparoscopic and vaginal, and robotic-assisted approaches may also be used. Compared with the abdominal radical hysterectomy (ARH), laparoscopic techniques are associated with less blood loss, shorter hospital stay, better cosmesis, and faster recovery. A further breakthrough in laparoscopic technique can only be made if safety and oncological clearance are comparable with ARH. We describe the technique and results of laparoscopic assisted radical vaginal hysterectomy and the transition to vaginal assisted laparoscopic radical hysterectomy. PMID- 22082330 TI - Bacterial vaginosis, Atopobium vaginae and nifuratel. AB - As bacterial vaginosis (BV) is a potential cause of obstetric complications and gynecological disorders, there is substantial interest in establishing the most effective treatment. Standard treatment - metronidazole or clindamycin, by either vaginal or oral route ? is followed by relapses in about 30% of cases, within a month from treatment completion. This inability to prevent recurrences reflects our lack of knowledge on the origins of BV. Atopobium vaginae has been recently reported to be associated with BV in around 80% of the cases and might be involved in the therapeutic failures. This review looks at the potential benefits of nifuratel against A. vaginae compared to the standard treatments with metronidazole and clindamycin. In vitro, nifuratel is able to inhibit the growth of A. vaginae, with a MIC range of 0.125-1 MUg/mL; it is active against G. vaginalis and does not affect lactobacilli. Metronidazole is active against A. vaginae only at very high concentrations (8-256 MUg/mL); it is partially active against G. vaginalis and also has no effect on lactobacilli. Clindamycin acts against A. vaginae with an MIC lower than 0.125 MUg/mL and is active on G. vaginalis but it also affects lactobacilli, altering the vaginal environment. These observations suggest that nifuratel is probably the most valid therapeutic agent for BV treatment. PMID- 22082332 TI - Nanoporous graphitic-C3N4@carbon metal-free electrocatalysts for highly efficient oxygen reduction. AB - Based on theoretical prediction, a g-C(3)N(4)@carbon metal-free oxygen reduction reaction (ORR) electrocatalyst was designed and synthesized by uniform incorporation of g-C(3)N(4) into a mesoporous carbon to enhance the electron transfer efficiency of g-C(3)N(4). The resulting g-C(3)N(4)@carbon composite exhibited competitive catalytic activity (11.3 mA cm(-2) kinetic-limiting current density at -0.6 V) and superior methanol tolerance compared to a commercial Pt/C catalyst. Furthermore, it demonstrated significantly higher catalytic efficiency (nearly 100% of four-electron ORR process selectivity) than a Pt/C catalyst. The proposed synthesis route is facile and low-cost, providing a feasible method for the development of highly efficient electrocatalysts. PMID- 22082333 TI - Microvesicles as novel biomarkers and therapeutic targets in transplantation medicine. AB - Microvesicles (MVs) including exosomes are emerging new biomarkers and potential regulators of inflammation and immunological processes. Such particles contain proteins and genetic information including DNA and microRNAs that may be of importance for cell/cell communication. However, their role during and after organ transplantation and immunomodulatory effects is only in its beginning of understanding. We here, in brief, introduce generation and biological importance of MVs, describe their (patho)physiological roles and their potential use as future biomarkers and therapeutic agents in transplantation medicine. Circulating MVs may have a great potential to detect possible immune rejections and MV modulation may emerge as a therapeutic approach in organ rejection therapy. PMID- 22082334 TI - 3D/4D sonography moved prenatal diagnosis of fetal anomalies from the second to the first trimester of pregnancy. AB - The introduction of 3D/4D sonography with high frequency transvaginal transducer has resulted in remarkable progress in ultrasonographic visualization of early embryos and fetuses and development of new fields of 3D sonoembryology. With the proper use of this new diagnostic modality and with experienced examiner, both structural and functional development in the first trimester of gestation can be assessed more objectively and reliable. Indeed new technology moved embryology from postmortem studies to the in vivo environment. Furthermore, there are good reasons to believe that 3D/4D sonography moved prenatal diagnosis of fetal abnormalities from the second to the first trimester of pregnancy. We will try to illustrate it with the number of convincing slides. PMID- 22082335 TI - Glutathione-deficient mice are susceptible to TCDD-Induced hepatocellular toxicity but resistant to steatosis. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) generates both hepatocellular injury and steatosis, processes that involve oxidative stress. Herein, we evaluated the role of the antioxidant glutathione (GSH) in TCDD-induced hepatotoxicity. Glutamate-cysteine ligase (GCL), comprising catalytic (GCLC) and modifier (GCLM) subunits, is rate limiting in de novo GSH biosynthesis; GCLM maintains GSH homeostasis by optimizing the catalytic efficiency of GCL holoenzyme. Gclm(-/-) transgenic mice exhibit 10-20% of normal tissue GSH levels. Gclm(-/-) and Gclm(+/+) wild-type (WT) female mice received TCDD for 3 consecutive days and were then examined 21 days later. As compared with WT littermates, Gclm(-/-) mice were more sensitive to TCDD-induced hepatocellular toxicity, exhibiting lower reduction potentials for GSH, lower ATP levels, and elevated levels of plasma glutamic oxaloacetic transaminase (GOT) and gamma-glutamyl transferase (GGT). However, the histopathology showed that TCDD-mediated steatosis, which occurs in WT mice, was absent in Gclm(-/-) mice. This finding was consistent with cDNA microarray expression analysis, revealing striking deficiencies in lipid biosynthesis pathways in Gclm(-/-) mice; qrt-PCR analysis confirmed that Gclm(-/ ) mice are deficient in expression of several lipid metabolism genes including Srebp2, Elovl6, Fasn, Scd1/2, Ppargc1a, and Ppara. We suggest that whereas GSH protects against TCDD-mediated hepatocellular damage, GSH deficiency confers resistance to TCDD-induced steatosis due to impaired lipid metabolism. PMID- 22082338 TI - Effects of denervation at ileocecal junction and ileocecal resection in dogs. AB - BACKGROUND: To investigate neural regulation at the ileocecal junction (ICJ) and motility changes after ileocecal resection (ICR). Previous studies showed normal basal motility at the ICJ directly by force transducers in dogs, but these observations were limited to normal contractile activity. METHODS: Continuous strain gauge recordings of stomach, terminal ileum, ileocecal sphincter (ICS), and colon were performed in dogs. The dogs were divided into four groups, namely control (CONT), extrinsic denervation at ICJ (ED), intrinsic denervation at ICJ (ID), and ICR groups. Colonic activity was recorded 2 h before a meal, in the early postprandial period (first 2 h), and in the late postprandial period (4-6 h after a meal). The meal lasted 5 min. KEY RESULTS: Motility index was significantly increased at the ICS (P = 0.0056) and proximal colon (P = 0.0059) after feeding. However, such changes were not observed in the ED and ID groups. The amplitude of contractions at proximal colon in the interdigestive state was significantly decreased by ED. In the ID and ICR groups, the numbers of nonmigrating contractions were significantly decreased (P < 0.05), and colonic migrating motor complex (CMMC) ratio was significantly higher than that of the CONT group (P < 0.001). The dogs in these two groups had diarrhea. CONCLUSIONS & INFERENCES: Gastrocolonic response at the ICJ may require both intrinsic and extrinsic innervation. When ID was performed, CMMC ratio increased. As a result, intraluminal water absorption may have decreased. ID may be one of the causes of diarrhea after ICR. PMID- 22082336 TI - Global assessment of genomic variation in cattle by genome resequencing and high throughput genotyping. AB - BACKGROUND: Integration of genomic variation with phenotypic information is an effective approach for uncovering genotype-phenotype associations. This requires an accurate identification of the different types of variation in individual genomes. RESULTS: We report the integration of the whole genome sequence of a single Holstein Friesian bull with data from single nucleotide polymorphism (SNP) and comparative genomic hybridization (CGH) array technologies to determine a comprehensive spectrum of genomic variation. The performance of resequencing SNP detection was assessed by combining SNPs that were identified to be either in identity by descent (IBD) or in copy number variation (CNV) with results from SNP array genotyping. Coding insertions and deletions (indels) were found to be enriched for size in multiples of 3 and were located near the N- and C-termini of proteins. For larger indels, a combination of split-read and read-pair approaches proved to be complementary in finding different signatures. CNVs were identified on the basis of the depth of sequenced reads, and by using SNP and CGH arrays. CONCLUSIONS: Our results provide high resolution mapping of diverse classes of genomic variation in an individual bovine genome and demonstrate that structural variation surpasses sequence variation as the main component of genomic variability. Better accuracy of SNP detection was achieved with little loss of sensitivity when algorithms that implemented mapping quality were used. IBD regions were found to be instrumental for calculating resequencing SNP accuracy, while SNP detection within CNVs tended to be less reliable. CNV discovery was affected dramatically by platform resolution and coverage biases. The combined data for this study showed that at a moderate level of sequencing coverage, an ensemble of platforms and tools can be applied together to maximize the accurate detection of sequence and structural variants. PMID- 22082339 TI - Myocardial recovery in peri-partum cardiomyopathy after continuous flow left ventricular assist device. AB - Left ventricular assist devices (LVADs) offer effective therapy for severe heart failure (HF) as bridge to transplantation or destination therapy. Rarely, the sustained unloading provided by the LVAD has led to cardiac reverse remodelling and recovery, permitting explantation of the device. We describe the clinical course of a patient with severe peri-partum cardiomyopathy (PPCM) rescued with a continuous flow LVAD, who experienced recovery and explantation. We discuss assessment of and criteria for recovery. PMID- 22082340 TI - Nutrition and udder health in dairy cows: a review. AB - Mastitis is still one of the three main diseases that affects the profitability of dairy farmers. Despite the implementation of the five-point mastitis control programme in the early 1970 s, the incidence in the UK has not reduced dramatically over the past 10 years. A review of the scientific literature indicates that there is a link between nutrition and mastitis in the dairy cow. The major impact of nutrition on udder health is via suppression of the immune system. Cows in negative energy balance are at a higher risk of ketosis and clinical ketosis is associated with a two-fold increase in the risk of clinical mastitis. Trace minerals and vitamins that can affect udder health are selenium and vitamin E, copper, zinc, and vitamin A and beta-carotene. PMID- 22082341 TI - East-West gradient in cardio-vascular mortality in Austria: how much can we explain by following the pattern of risk factors? AB - BACKGROUND: Various studies show major regional differences in the prevalence of cardio-vascular disease morbidity and mortality, both in Europe and within European countries. In Austria, these differences are documented by an East-West gradient with declining morbidity and mortality rates when moving from the East to the West of the country. It was the aim of this study to analyse if, and to what extent, socio-demographic and socio-economic determinants, social resources and health behaviour can contribute to the clarification of this East-West gradient by conducting secondary analyses of an existing Austrian health dataset. RESULTS: The data were analysed using bivariate analyses, as well as univariate and multivariate logistic regression models. These analyses revealed significant East-West gradients for various risk factors, as well as socio-demographic and socio-economic health determinants. There was a gradual decrease of hypertension, diabetes mellitus, obesity, and psycho-social discomfort in both sexes, with the highest prevalences in those Austrian regions with the highest cardio-vascular mortality and a stepwise decrease to the regions with the lowest cardio-vascular mortality. Controlling for educational level significantly raised the odds for diabetes, hypertension and obesity. In the results of the multivariate analyses, factors that significantly and independently predicted diabetes mellitus were geographic location, psycho-social discomfort, lack of physical exercise, and age in both sexes. For women these factors additionally included a low educational level, lack of social support, and being born abroad. CONCLUSIONS: Our study shows a clear gradual decline of cardio-vascular mortality and some of its risk factors from East to West in Austria. Concerning these risk factors, the geographic region and psycho-social discomfort showed the greatest association with diabetes mellitus, hypertension, and obesity. Hence, they contribute to the explanation of the variance in spatial cardio-vascular disease mortality. Yet, a large proportion of this variance remains unexplained. It would be of great importance to public health and preventive measures to take a closer look at spatial differences in cardio-vascular disease morbidity and mortality to better tailor programmes to the regional environments and settings. Our results also call for a greater importance of preventative measures for psycho-social discomfort and increase of social support. PMID- 22082342 TI - Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti-HBc titres or high anti-HBc titres with high anti-HBs titres in Japan: a prospective, individual NAT study of transfusion-transmitted HBV, HCV and HIV infections. AB - BACKGROUND: The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion-transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. STUDY DESIGN AND METHODS: Post-transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre-transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre-transfusion specimen was non-reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti-HBc titres or high anti-HBc with high anti HBs titres. RESULTS: Transfusion-transmitted HCV and HIV infections were not observed. One case of post-transfusion HBV infection was identified (rate, 0.0004675; 95% CI for the risk of transmission, 1 in 451-41,841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3.4% (72/2139), 7.2% (150/2091) and 0% (0/2040), respectively. Sixty-four anti-HBc- and/or anti-HBs-reactive blood components were transfused to 52 patients non reactive for anti-HBc or anti-HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). CONCLUSION: This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant. PMID- 22082343 TI - Are the symptoms of cannabis use disorder best accounted for by dimensional, categorical, or factor mixture models? A comparison of male and female young adults. AB - Despite the consensus that criteria for cannabis abuse and dependence and symptoms of withdrawal are best explained by a single latent liability, it remains unknown whether alternative models provide a better explanation of these criteria. A series of latent factor, latent class, and hybrid factor mixture models were fitted to data from 872 recent cannabis users from the Minnesota Twin Family Study who completed Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised, and 4th ed.) diagnostic criteria for cannabis abuse, dependence, and symptoms of withdrawal. Despite theoretical appeal, results did not support latent class or factor mixture modeling. Instead, symptoms of abuse, dependence, and withdrawal were better summarized by a single latent factor Cannabis Use Disorder (CUD) for male and female young adults. An almost 2-fold sex difference in item endorsement was best explained by a single mean difference on the CUD factor, indicating that young men have a greater latent liability toward expressing CUD. PMID- 22082344 TI - Reliability and validity of young adults' anonymous online reports of marijuana use and thoughts about use. AB - With growing interest in online assessment of substance abuse behaviors, there is a need to formally evaluate the validity of the data gathered. The current investigation evaluated the reliability and validity of anonymous, online reports of young adults' marijuana use and related cognitions. Young adults age 18 to 25 who had smoked at least one cigarette in the past 30 days were recruited over 14 months to complete an anonymous online survey. Of 3,106 eligible cases, 1,617 (52%) completed the entire survey. Of those, 54% (n = 884) reported past-month marijuana use (65% male, 70% Caucasian, mean age was 20.4 years [SD = 2.0]). Prevalence of marijuana use was reported reliably across three similar items, and interitem correlations ranged from fair to excellent for measures of marijuana dependence symptoms and thoughts about marijuana use. Marijuana use frequency demonstrated good construct validity through expected correlations with marijuana use constructs, and nonsignificant correlations with thoughts about tobacco use. Marijuana frequency distinguished among stages of change for marijuana use and goals for use, but not among gender, ethnicity, or employment groups. Marijuana use and thoughts about use differed by stage of change in the hypothesized directions. Self-reported marijuana use and associated cognitions reported anonymously online from young adults are generally reliable and valid. Online assessments of substance use broaden the reach of addictions research. PMID- 22082345 TI - The nature of coping in treatment for marijuana dependence: latent structure and validation of the Coping Strategies Scale. AB - The Coping Strategies Scale (CSS) was designed to assess adaptive changes in substance-use specific coping that result from treatment. This study sought to examine the latent structure of the CSS in the hope that it might shed light on the coping processes of drug users and guide the development of a brief version of the CSS. Respondents on the CSS were 751 men and women treated in 3 clinical trials for marijuana dependence. Posttreatment CSS data were analyzed to determine the nature of coping responses in patients who have been trained to use specific strategies to deal with substance use disorders. Exploratory factor analysis yielded 2 factors, categorized as problem-focused and emotion-focused coping, but confirmatory factor analysis did not support this structure. When infrequently endorsed items were removed, however, confirmatory factor analysis revealed a good fit to the data. Contrary to expectations, practical strategies that often form the basis for coping skills training, such as avoiding those who smoke, were not frequently endorsed. Problem-focused items reflected cognitive commitments to change. Emotion-focused items included cognitive reinterpretations of emotions to help manage emotional reactions. Brief versions of the CSS based on these factors showed good convergent and discriminant validity. The CSS, and the brief versions of the CSS, may prove useful in future treatment trials to evaluate effects of treatment on coping skills acquisition and utilization in substance dependent individuals. PMID- 22082346 TI - Successful catheter cryoablation of Hisian ectopy using 2 new diagnostic criteria based on unipolar and bipolar recordings of the His electrogram. AB - We describe the case of a 61-year-old woman who underwent successful catheter cryoablation of a symptomatic Hisian ectopy. Diagnosis was based on features of the HV interval assessed from a bipolar recording during mapping. The location of the arrhythmic focus was identified using simultaneous unipolar and bipolar recordings of the His electrogram. This case report highlights the use of 2 new criteria for the diagnosis and mapping of Hisian ectopy, and the successful use of cryothermia for the ablation of extrasystoles arising from the His bundle. PMID- 22082347 TI - Developing a minimum data set for electronic nursing handover. AB - AIMS AND OBJECTIVES: This study presents a minimum data set designed for an electronic system to complement verbal nursing handover. Background. Poor communication of patient information at handover has been implicated in adverse events with changes to clinical handover being proposed as a solution. This study developed a minimum data set for an electronic patient summary tool. DESIGN; Using an observational design the scope of information being presented by nurses at handover was identified in relation to a generic Nursing Handover Minimum Data Set. METHOD: Patient handovers (n = 195) were observed and digitally recorded across diverse specialties. RESULTS: Content analysis confirmed the frequent use of the Nursing Handover Minimum Data Set items across all specialties. The use of the items was affected by the patient context and the clinical setting. Aged care patients often had several clinical alerts reported (pressure areas, falls risk). Rapid changes in patient condition in emergency emphasised the need for a focus on observations and presenting problems. Mental health and maternity required further refinement of the items. CONCLUSION: The generic Nursing Handover Minimum Data Set can direct nurses to give a comprehensive account of their patient's condition and care. The data set needs to be flexible and adaptable to the patient context and setting and complements structured content verbal handover. This minimum data set provides an excellent framework for system development by clinicians, managers and information technologists. Educators can use this tool to teach student nurses, new graduates and experienced staff, about the patient information to be presented at handover. RELEVANCE TO CLINICAL PRACTICE: The Nursing Handover Minimum Data Set for electronic nursing handover complements verbal handover and provides a tool to give clinicians access to comprehensive information about all patients within the ward area. PMID- 22082349 TI - Protective effects of Rg2 on hypoxia-induced neuronal damage in hippocampal neurons. AB - We investigated the neuroprotective effects of Rg(2) in anoxic cultured hippocampal neurons of newborn rats. The cells were divided into a control group, nimodipine group (5 MUmol/L), Rg(2) (0.025 mmol/L), and Rg(2) (0.05 mmol/L) group. The apoptosis rate of hippocampal neurons was measured by flow cytometry with staining of PI. The intracellular calcium ion [Ca(2+)]i was observed with fluorospectrophotometer determined by fluorescent probe Fluo-2/AM. The contents of MDA and NO and the activities of SOD in the supernatants of cells were determined by biochemical methods. The results demonstrated that Rg(2) reduced the hypoxia-induced apoptosis, decreased the calcium overload in neurons, increased the activities of SOD, and decreased the contents of MDA and NO in the supernatants of cells. Our study suggests that Rg(2) has a neuroprotective effect against hypoxia-induced neuronal damage in hippocampal neurons mediated by anti apoptosis, blocking calcium over-influx into neuronal cells, eliminating the free radicals, and increasing the activities of anti-oxidative enzymes to inhibit the oxidative damages caused by anoxic. PMID- 22082350 TI - Emission mechanism of polyatomic ions Cs2Cl+ and Cs2BO2(+) in thermal ionization mass spectrometry with various carbon materials. AB - The emission behavior of polyatomic ions Cs(2)Cl(+) and Cs(2)BO(2)(+) in the presence of various carbon materials (Graphite, Carbon, SWNTs, and Fullerenes) in the ionization source of thermal ionization mass spectrometry (TIMS) has been investigated. The emission capacity of various carbon materials are remarkably different as evidenced by the obvious discrepancy in signal intensity of polyatomic ions and accuracy/precision of boron and chlorine isotopic composition determined using Cs(2)Cl(+)-graphite-PTIMS/Cs(2)BO(2)(+)-graphite-PTIMS methods. Combined with morphology and microstructure properties of four selected carbon materials, it could be concluded that the emission behavior of the polyatomic ions strongly depends on the microstructure of the carbon materials used. A surface-induced collision mechanism for formation of such kinds of polyatomic ions in the ionization source of TIMS has been proposed based on the optimized configuration of Cs(2)BO(2)(+) and Cs(2)Cl(+) ions in the gas phase using a molecular dynamics method. The combination of the geometry of the selected carbon materials with the configuration of two polyatomic ions explains the structure effect of carbon materials on the emission behavior of polyatomic ions, where graphite samples with perfect parallels and equidistant layers ensure the capacity of emission to the maximum extent, and fullerenes worsen the emission of polyatomic ions by blocking their pathway. PMID- 22082348 TI - Epigenetic modifications in cancer. AB - Cancer initiation and progression is controlled by both genetic and epigenetic events. The complexity of carcinogenesis cannot be accounted for by genetic alterations alone but also involves epigenetic changes. Epigenetics refers to the study of mechanisms that alter gene expression without altering the primary DNA sequence. Epigenetic mechanisms are heritable and reversible, and include changes in DNA methylation, histone modifications and small noncoding microRNAs (miRNA). Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Aberrant epigenetic modifications probably occur at a very early stage in neoplastic development, and they are widely described as essential players in cancer progression. Recent advances in epigenetics offer a better understanding of the underlying mechanism(s) of carcinogenesis and provide insight into the discovery of putative cancer biomarkers for early detection, disease monitoring, prognosis, and risk assessment. In this review, we summarize the current literature on epigenetic changes causing genetic alterations that are thought to contribute to cancer, and discuss the potential impact of epigenetics future research. PMID- 22082351 TI - The potential role of the lectin pathway of complement in the host defence of full-term intrauterine growth restricted neonates at birth. AB - OBJECTIVE: To prospectively investigate the potential role of the lectin pathway of complement in intrauterine-growth-restriction (IUGR, associated with impaired immunocompetence and increased risk for neonatal infections), by determining cord blood concentrations of mannose-binding lectin (MBL), H-ficolin and L-ficolin (important mediators of neonatal innate immunity) in IUGR and appropriate for gestational age (AGA) pregnancies. Furthermore, we aimed to describe correlations among cord blood MBL, H- and L-ficolin concentrations and with several demographic parameters of the infants at birth. METHODS: Serum MBL, H- and L ficolin concentrations were determined by ELISA in 154 mixed arteriovenous cord blood samples from IUGR (n = 50) and AGA (n = 104) singleton full-term infants. RESULTS: Cord blood MBL concentrations were significantly lower in IUGR cases than AGA controls (p = 0.029). No differences in cord blood H- and L-ficolin concentrations were observed between groups. In the IUGR group, cord blood MBL concentrations negatively correlated with respective L-ficolin ones (r = -0.442, p = 0.001). CONCLUSIONS: The relatively decreased MBL expression in IUGR fetuses at term could possibly contribute to IUGR-associated neonatal immunodeficiency, predisposing to increased susceptibility to infections. The negative correlation between MBL and L-ficolin concentrations in the IUGR group might suggest an underlying immune variation and needs to be further investigated. PMID- 22082352 TI - Determination of water-soluble arsenic compounds in commercial edible seaweed by LC-ICPMS. AB - This paper reports arsenic speciation in edible seaweed (from the Galician coast, northwestern Spain) produced for human consumption. Chondrus crispus , Porphyra purpurea , Ulva rigida , Laminaria ochroleuca , Laminaria saccharina , and Undaria pinnatifida were analyzed. The study focused on arsenosugars, the most frequently occurring arsenic species in algae. As(III) and As(V) were also determined in aqueous extracts. Total arsenic in the samples was determined by microwave digestion and inductively coupled plasma mass spectrometry (ICPMS). For arsenic speciation, a water extraction especially suitable for arsenosugars was used, and the arsenic species were analyzed by liquid chromatography with both anionic and cationic exchange and ICPMS detection (LC-ICPMS). The total arsenic content of the alga samples ranged from 5.8 to 56.8 mg As kg(-1). The mass budgets obtained in the extracts (column recovery * extraction efficiency) ranged from 38 to 92% except for U. pinnatifida (4%). The following compounds were detected in the extracts: arsenite (As(III)), arsenate (As(V)), methylarsonate (MA), dimethylarsinate (DMA), sulfonate sugar (SO(3)-sug), phosphate sugar (PO(4) sug), arsenobetaine (AB), and glycerol sugar (Gly-sug). The highest concentrations corresponded to the arsenosugars. PMID- 22082353 TI - Altered physiology of acid secretion in depression-prone Flinders rats results in exacerbated NSAID and stress-induced gastric damage. AB - BACKGROUND: Flinders Sensitive Line (FSL) rats are characterized by hypersensitivity to cholinergic stimuli and have been extensively used for studying depressive disorders. A link between depression and peptic ulcers has long been established; however, there is a lack of data from animal models. METHODS: We studied the physiology of acid secretion in FSL and Flinders Resistant Line (FRL) rats in vivo and in vitro. We also examined the susceptibility of Flinders rats to water immersion restraint stress (WIRS) or NSAID-induced gastric damage and explored the effect of an anticholinergic agent, atropine, in reversing this effect. KEY RESULTS: Basal acid output was more than twofold greater in FSL compared with FRL rats in vivo, 213.5 and 92.8 MUEq/3 h/100 g (P = 0.02), respectively. Carbachol was a more potent secretagog in vitro, and somatostatin was a less potent inhibitory agent, while paradoxically stimulating acid secretion over and above the carbachol response in gastric glands from FSL rats. The FSL rats were more susceptible to indomethacin and WIRS induced gastric mucosal damage compared with FRL rats. Atropine reduced acid output, which resulted in a reduction in indomethacin and stress-induced gastric damage in FSL rats. CONCLUSIONS & INFERENCES: Our study, for the first time, demonstrates that the altered vagally mediated physiology of acid secretion in depression-prone FSL rats contributes to gastric hypersecretion and, consequently, results in exacerbated stress and NSAID-induced gastric damage. Flinders rats may be a useful animal model for studying acid-related and also gastrointestinal functional disorders in depression. PMID- 22082354 TI - Human intravenous immunoglobulins suppress seizure activities and inhibit the activation of GFAP-positive astrocytes in the hippocampus of picrotoxin-kindled rats. AB - We previously showed that human intravenous immunoglobulin (IVIG) can lower seizure severity and prolong seizure latency in picrotoxin-kindled rats. The aim of this study was to further characterize the effects of IVIG on seizure activity and investigate its influence on astrocytes in the hippocampus of picrotoxin kindled rats. A rat kindling model was established by peritoneal injections of picrotoxin for 21 days in Wistar rats. Seventy-five rats were equally divided into five groups: picrotoxin, IVIG pretreatment, IVIG post-treatment, normal saline control, and IVIG control. Seizure severity was evaluated according to a six-stage classification. The number and morphology of glial fibrillary acidic protein (GFAP)-positive astrocytes were studied by immunohistochemistry using the anti-GFAP antibody. The cross-sectional area and grayscale of GFAP-positive astrocytes were also determined. In picrotoxin-kindled rats, pretreatment with IVIG appeared to inhibit full kindling rates, and it significantly reduced the number of GFAP-positive cells in the hippocampus (p < .001). IVIG also significantly (p < .001) attenuated the increase in the cross-sectional area and grayscale of GFAP-positive astrocytes in the hippocampus. Our results suggest that by suppressing the expression of GFAP, IVIGs may reduce seizure activity and inhibit the activation of GFAP-positive astrocytes in picrotoxin-kindled rats. PMID- 22082355 TI - Are there independent predisposing factors for postoperative infections following open heart surgery? AB - BACKGROUND: Nosocomial infections after cardiac surgery represent serious complications associated with substantial morbidity, mortality and economic burden. This study was undertaken to evaluate the frequency, characteristics, and risk factors of microbiologically documented nosocomial infections after cardiac surgery in a Cardio-Vascular Intensive Care Unit (CVICU). METHODS: All patients who underwent open heart surgery between May 2006 and March 2008 were enrolled in this prospective study. Pre-, intra- and postoperative variables were collected and examined as possible risk factors for development of nosocomial infections. The diagnosis of infection was always microbiologically confirmed. RESULTS: Infection occurred in 24 of 172 patients (13.95%). Out of 172 patients, 8 patients (4.65%) had superficial wound infection at the sternotomy site, 5 patients (2.9%) had central venous catheter infection, 4 patients (2.32%) had pneumonia, 9 patients (5.23%) had bacteremia, one patient (0.58%) had mediastinitis, one (0.58%) had harvest surgical site infection, one (0.58%) had urinary tract infection, and another one patient (0.58%) had other major infection. The mortality rate was 25% among the patients with infection and 3.48% among all patients who underwent cardiac surgery compared with 5.4% of patients who did not develop early postoperative infection after cardiac surgery. Culture results demonstrated equal frequencies of gram-positive cocci and gram-negative bacteria. A backward stepwise multivariable logistic regression model analysis identified diabetes mellitus (OR 5.92, CI 1.56 to 22.42, p = 0.009), duration of mechanical ventilation (OR 1.30, CI 1.005 to 1.69, p = 0.046), development of severe complications in the CICU (OR 18.66, CI 3.36 to 103.61, p = 0.001) and re admission to the CVICU (OR 8.59, CI 2.02 to 36.45, p = 0.004) as independent risk factors associated with development of nosocomial infection after cardiac surgery. CONCLUSIONS: We concluded that diabetes mellitus, the duration of mechanical ventilation, the presence of complications irrelevant to the infection during CVICU stay and CVICU re-admission are independent risk factors for the development of postoperative infection in cardiac surgery patients. PMID- 22082358 TI - Rosalyn Sussman Yalow: Bronx gal who made great. PMID- 22082356 TI - The MetJ regulon in gammaproteobacteria determined by comparative genomics methods. AB - BACKGROUND: Whole-genome sequencing of bacteria has proceeded at an exponential pace but annotation validation has lagged behind. For instance, the MetJ regulon, which controls methionine biosynthesis and transport, has been studied almost exclusively in E. coli and Salmonella, but homologs of MetJ exist in a variety of other species. These include some that are pathogenic (e.g. Yersinia) and some that are important for environmental remediation (e.g. Shewanella) but many of which have not been extensively characterized in the literature. RESULTS: We have determined the likely composition of the MetJ regulon in all species which have MetJ homologs using bioinformatics techniques. We show that the core genes known from E. coli are consistently regulated in other species, and we identify previously unknown members of the regulon. These include the cobalamin transporter, btuB; all the genes involved in the methionine salvage pathway; as well as several enzymes and transporters of unknown specificity. CONCLUSIONS: The MetJ regulon is present and functional in five orders of gammaproteobacteria: Enterobacteriales, Pasteurellales, Vibrionales, Aeromonadales and Alteromonadales. New regulatory activity for MetJ was identified in the genomic data and verified experimentally. This strategy should be applicable for the elucidation of regulatory pathways in other systems by using the extensive sequencing data currently being generated. PMID- 22082359 TI - Fibrodysplasia ossificans progressiva: a blueprint for metamorphosis. AB - The most important milestone in understanding a genetic disease is the identification of the causative mutation. However, such knowledge is often insufficient to decipher the pathophysiology of the disorder or to effectively treat those affected. Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling, genetic disease of progressive heterotopic endochondral ossification (HEO) enabled by missense mutations that promiscuously and provisionally activate ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor, in all affected individuals. While activating mutations of the ACVR1/ALK2 receptor are necessary, disease activity and progression also depend on altered cell and tissue physiology. Recent findings identify inflammatory and immunological factors, vascular-derived mesenchymal stem cells, and a hypoxic lesional microenvironment that trigger, promote, and enable episodic progression of FOP in the setting of the genetic mutation. Effective therapies for FOP will need to consider these seminal pathophysiologic interactions. PMID- 22082360 TI - Combinatorial control of ATF4-dependent gene transcription in osteoblasts. AB - Osteoblast-specific gene transcription requires interaction between bone cell specific transcription factors and more widely expressed transcriptional regulators. This is particularly evident for the basic domain-leucine zipper factor activating transcription factor 4 (ATF4), whose activity can be enhanced or inhibited through interaction with other leucine zipper proteins, intermediate filament proteins, components of the basic transcriptional machinery, nuclear matrix attachment molecules, or ubiquitously expressed transcription factors. We discuss the results supporting the relevance of these interactions and present the first evidence of a functional interaction between ATF4, FIAT (factor inhibiting ATF4-mediated transcription), and alphaNAC (nascent polypeptide associated complex and coactivator alpha), three proteins that have been previously shown to associate using various protein-protein interaction assays. PMID- 22082357 TI - Endothelial dysfunction in the apolipoprotein E-deficient mouse: insights into the influence of diet, gender and aging. AB - Since the early 1990s, several strains of genetically modified mice have been developed as models for experimental atherosclerosis. Among the available models, the apolipoprotein E-deficient (apoE-/-) mouse is of particular relevance because of its propensity to spontaneously develop hypercholesterolemia and atherosclerotic lesions that are similar to those found in humans, even when the mice are fed a chow diet. The main purpose of this review is to highlight the key achievements that have contributed to elucidating the mechanisms pertaining to vascular dysfunction in the apoE-/- mouse. First, we summarize lipoproteins and atherosclerosis phenotypes in the apoE-/- mouse, and then we briefly discuss controversial evidence relative to the influence of gender on the development of atherosclerosis in this murine model. Second, we discuss the main mechanisms underlying the endothelial dysfunction of conducting vessels and resistance vessels and examine how this vascular defect can be influenced by diet, aging and gender in the apoE-/- mouse. PMID- 22082361 TI - Sclerostin is overexpressed by plasma cells from multiple myeloma patients. AB - Sclerostin, an osteocyte-expressed negative regulator of bone formation, is one of the inhibitors of Wnt signaling that is a critical pathway in the correct process of osteoblast differentiation. It has been demonstrated that Wnt signaling through the secretion of Wnt inhibitors, such as DKK1, sFRP-2, and sFRP 3, plays a key role in the decreased osteoblast activity associated with multiple myeloma (MM) bone disease. We provide evidence that sclerostin is expressed by myeloma cells that are human myeloma cell lines and plasma cells (CD138(+) cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. Moreover, we show that there are no differences in sclerostin serum levels between MM patients and controls. Thus, our data indicate that MM cells, as a sclerostin source in the BM, could create a microenvironment with high sclerostin concentration that could contribute toward inhibiting osteoblast differentiation. PMID- 22082362 TI - Transcription factors in parathyroid development: lessons from hypoparathyroid disorders. AB - Parathyroid developmental anomalies, which result in hypoparathyroidism, are common and may occur in one in 4,000 live births. Parathyroids, in man, develop from the endodermal cells of the third and fourth pharyngeal pouches, whereas, in the mouse they develop solely from the endoderm of the third pharyngeal pouches. In addition, neural crest cells that arise from the embryonic mid- and hindbrain also contribute to parathyroid gland development. The molecular signaling pathways that are involved in determining the differentiation of the pharyngeal pouch endoderm into parathyroid cells are being elucidated by studies of patients with hypoparathyroidism and appropriate mouse models. These studies have revealed important roles for a number of transcription factors, which include Tbx1, Gata3, Gcm2, Sox3, Aire1 and members of the homeobox (Hox) and paired box (Pax) families. PMID- 22082363 TI - Antagonists of LRP6 regulate PTH-induced cAMP generation. AB - LRP6 is a common coreceoptor for different G protein-coupled seven-transmembrane receptors in production of cAMP. Extracelluar proteins sclerostin and DKK1, initially identified as antagonists for Wnt signaling by binding to LRP6, are negative regulators for bone formation. Here, we show that both sclerostin and DKK1 inhibit PTH-stimulated cAMP production. In addition, PTH suppresses expression of sclerostin in osteocytes in mice. We also found that sclerostin and DKK1 binds to LRP6 as antagonists to increase the availability of LRP6 to facilitate PTH signaling in a positive-feedback fashion. These studies reveal a previously unrecognized function of sclerostin and DKK1, which provides an alternative explanation for the application of sclerostin and DKK1 neutralization on enhancing bone formation as a potential therapy for skeletal diseases. PMID- 22082364 TI - Dental pulp stem cells: osteogenic differentiation and gene expression. AB - Dental pulp stem cells (DPSCs) are an adult stem cell population with high proliferative potential and the ability to differentiate in many cell types, and this has led scientists to consider these cells to be an alternative source of postnatal stem cells comparable to mesenchymal stem cells from bone marrow. In this work, we studied the osteoblastic phenotype developed by DPSCs cultured in osteogenic medium. In particular, we analyzed the expression of the typical osteoblast markers such as alkaline phosphatase, collagen type I, osteocalcin, osteopontin, as well as mineralized matrix production. Furthermore, the gene expression during DPSC differentiation into osteoblastic cells was studied by microarray technology. Using microarray and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we found that IGFBP-5, JunB, and NURR1 genes are upregulated during the differentiation of DPSCs. These data indicate that opportunely differentiated DPSCs show a correct osteoblastic phenotype. Therefore, during the osteoblastic differentiation process, IGFBP-5, JunB, and NURR1 gene expression is significantly increased. PMID- 22082365 TI - Adrenergic stimulation decreases osteoblast oxytocin synthesis. AB - Oxytocin (OT) regulates bone mass by inducing the differentiation of osteoblasts to a mature, mineralizing phenotype. We have shown recently that osteoblasts can synthesize OT. In view of known interactions between OT-ergic and adrenergic neurons in the central nervous system, we questioned whether the negative regulation of osteoblast differentiation by adrenergic nerves was mediated through its suppression of OT synthesis. We first confirmed that alpha(1b) and beta(2) adrenergic receptors were expressed on both primary murine osteoblasts and MC3T3-E1 cells. We then showed that alpha(1) and beta(2) adrenergic agonists downregulated OT synthesis, and that the effect of each agonist was reversed by its respective antagonist. The data suggest that the negative effects of adrenergic stimulation on bone mass could, in part, arise from decreased OT synthesis. PMID- 22082366 TI - An essential role for the circadian-regulated gene nocturnin in osteogenesis: the importance of local timekeeping in skeletal homeostasis. AB - The role of circadian proteins in regulating whole-body metabolism and bone turnover has been studied in detail and has led to the discovery of an elemental system for timekeeping involving the core genes Clock, Bmal1, Per, and Cry. Nocturnin (Noc; Ccrn4l), a peripheral circadian-regulated gene has been shown to play a very important role in regulating adipogenesis by deadenylation of key mRNAs and intracytoplasmic transport of PPARgamma. The role that it plays in osteogenesis has previously not been studied in detail. In this report we examined in vitro and in vivo osteogenesis in the presence and absence of Noc and show that loss of Noc enhances bone formation and can rescue rosiglitazone induced bone loss in mice. The circadian rhythm of Noc is likely to be an essential element of marrow stromal cell fate. PMID- 22082367 TI - Prostatic acid phosphatase is expressed in human prostate cancer bone metastases and promotes osteoblast differentiation. AB - Prostate cancer (PCa) bone metastases are a major cause of morbidity and mortality. There are no effective therapies for PCa bone metastases that prolong survival. Prostatic acid phosphatase (PAP) is a secretory protein expressed by PCa cells. We demonstrate that PAP is strongly expressed in PCa bone metastases in 7/7 patients, while prostate-specific antigen (PSA) is only weakly expressed. The human PCa cell line VCaP secretes PAP and induces an osteoblastic reaction in bone similar to that seen in human PCa bone metastases. Coculture of MC3T3 mouse preosteoblast cells with VCaP cells induces MC3T3 cell growth and differentiation as measured by alkaline phosphatase secretion, and this effect is inhibited by addition of the PAP-inhibitor, l-tartrate. Taken together, these data indicate that PAP is expressed in PCa bone metastases and may play a causal role in the osteoblastic phase of the disease. PMID- 22082368 TI - Immune regulation of the tumor/bone vicious cycle. AB - The bone destruction attending skeletal metastasis is mediated by tumor-recruited osteoclasts (OCs). Hence, OCs are principal therapeutic targets in afflicted individuals. On the other hand, one-third of patients develop further skeletal related events within two years of initiating antiresorptive therapies, suggesting that additional cells modulate bone tumor growth. Previous studies showing amelioration of bone metastases by targeting the OCs were performed in immune-compromised animals injected with human breast cancer cells. Consequently, the contribution of the immune system to bone tumor growth was unclear. Using genetic models of immune and OC modulation (PLCgamma2 and Lyn), as well as pharmacological inhibition of OCs and T cells, we now demonstrate that a condition of immune deficiency can interfere with the antitumor effects of OC blockade. Thus, our findings expand the current tumor/bone vicious cycle model to include T cells as additional regulators of bone tumor growth, regardless of the OC status. PMID- 22082369 TI - Altered matrix at the chondro-osseous junction leads to defects in lymphopoiesis. AB - The collagen X transgenic and null (ColX-Tg/KO) mice have revealed a link between endochondral ossification (EO) and hematopoiesis, and thus serve as model systems to study hematopoietic niches. The altered collagen X function in ColX-Tg/KO mice resulted not only in skeletal defects, which included changes in growth plate ultrastructure, altered localization of heparan sulfate proteoglycans (HSPG), and reduced trabecular bone, but also in hematopoietic defects, which included reduced B lymphocyte numbers throughout life without associated increases in B cell apoptosis. Consequently, the ColX-Tg/KO mice exhibited diminished in vitro and in vivo immune responses. Moreover, reduced expression of several hematopoietic and B lymphopoietic cytokines were measured from ColX-KO-derived hypertrophic chondrocyte and trabecular osteoblast cultures. Together, these data expand the current hematopoietic niche model by including the EO-derived extracellular matrix, for example, the collagen X/HSPG network, as well as the EO derived hypertrophic chondrocytes and trabecular osteoblasts as hematopoietic signal mediating cells. PMID- 22082370 TI - Feedback inhibition of osteoclastogenesis during inflammation by IL-10, M-CSF receptor shedding, and induction of IRF8. AB - Inflammation plays a key role in excessive bone loss in conditions such as rheumatoid arthritis and periodontitis. An important paradigm in immunology is that inflammatory factors activate feedback inhibition mechanisms to restrain inflammation and limit associated tissue damage. We hypothesized that inflammatory factors would activate similar feedback mechanisms to restrain bone loss in inflammatory settings. We have identified three mechanisms that inhibit osteoclastogenesis and are induced by inflammatory factors such as toll-like receptor ligands and cytokines; downregulation of expression of costimulatory molecules such as TREM-2; induction of shedding, and thereby inactivation of the M-CSF receptor c-Fms, leading to decreased RANK transcription; and induction of transcriptional repressors such as interferon regulatory factor 8. It is likely that these mechanisms work in a complementary and cooperative manner to fine tune the extent of osteoclastogenesis in inflammatory settings, and their augmentation may represent an alternative therapeutic approach to suppress bone resorption. PMID- 22082371 TI - Translational musculoskeletal science: is sarcopenia the next clinical target after osteoporosis? AB - Translational medicine must increasingly turn its attention to the aging population and the musculoskeletal deterioration that it entails. The latter involves the integrated function of both muscle and bone. Musculoskeletal science has an established interest in such problems in relationship to osteoporosis of bone. The introductory concepts in this paper consider the extent to which loss of muscle mass and function, or sarcopenia, will be the next major translational target. Its epidemiology shows parallels with that of osteoporosis, and the two tissues have a close functional relationship. Its etiology likely involves a loss of motor units combined with cellular signaling and endocrine changes. Finally, the possibility of modification of these physiological changes in the context of management of the sarcopenic condition is considered. PMID- 22082372 TI - HACCP-based quality risk management approach to udder health problems on dairy farms. AB - Against the background of prevailing udder health problems on dairy farms, this paper discusses a new approach to mastitis control. Current udder health control programmes, such as the 'five-point plan', are highlighted and their drawbacks indicated. The concept and principles of hazard analysis critical control points (HACCP) are introduced. The eight core elements of this concept are dealt with by using the example of a dairy herd with a mastitis problem due to Staphylococcus aureus. The various steps to be taken in the development of a HACCP-based quality risk management programme are illustrated through the application of core elements. Finally, it is shown that the HACCP key words, structure, organisation, planning, communication and formalisation; which do not frequently appear in conventional herd health and production management programmes can contribute to better udder health. The role of the veterinarian can be paramount and of added value, if he/she is willing to invest in new knowledge and skills, such as the HACCP concept, farm economics, animal nutrition, and particularly the role of coach to the dairy farmer in the implementation of preventative measures in relation to udder health. PMID- 22082373 TI - Sudden modification in QRS morphology during entrainment of ventricular tachycardia: what is the mechanism? PMID- 22082377 TI - Carol S. Dweck: Award for Distinguished Scientific Contributions. AB - Presents Carol S. Dweck, 2011 winner of the American Psychological Association Award for Distinguished Scientific Contributions. "For her insightful research and incisive theorizing concerning perceptions and interpretations of success and failure across many domains of human endeavor, but especially in the realm of academic achievement. Drawing on a series of innovative and elegant experimental paradigms, Carol S. Dweck has cast a theoretical net progressing from initial studies of learned helplessness to studies of the larger self-theories of ability, the activity goals individuals select, and the differential consequences associated with helpless versus mastery-oriented responses to difficult problems. Her widely cited work has produced, in addition, clever and effective strategies for promoting more functional incremental theories, learning goals, and persistence in students facing apparent failure." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082378 TI - Barry J. Everitt: Award for Distinguished Scientific Contributions. AB - Presents Barry J. Everitt, 2011 winner of the American Psychological Association Award for Distinguished Scientific Contributions. "For distinguished theoretical and empirical contributions to basic research in experimental psychology and neuroscience. Barry J. Everitt's original and elegant research has greatly added to the understanding of monoaminergic and glutamatergic regulation of cortico striatal-limbic function and its involvement in psychological processes and pathological states, notably addiction. His stellar contributions have included the development of animal models of addiction and groundbreaking studies on learning and memory processes. He has combined sophisticated behavioral approaches with molecular, cellular, anatomical, and psychopharmacological approaches in rodents. His energy and enthusiasm for research, creativity, and outstanding productivity have advanced our knowledge of brain function and inspired several generations of behavioral neuroscientists." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082379 TI - Trevor W. Robbins: Award for Distinguished Scientific Contributions. AB - Presents Trevor W. Robbins, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Contributions."For distinguished theoretical and empirical contributions to basic research in experimental psychology and neuroscience. Trevor W. Robbins has made innovative and landmark contributions to understanding monoaminergic and glutamatergic regulation of cortico-striatal-limbic function and its involvement in psychological processes and pathological states such as addiction, depression, schizophrenia, and attention-deficit/hyperactivity disorder. His pioneering accomplishments have included the development of methodologies for parallel sophisticated behavioral assessments in humans, rodents, and monkeys combined with psychopharmacological and imaging studies across species. His vigor and dedication to research, exemplary leadership, scholarship, and stellar productivity have advanced our knowledge of brain function and inspired several generations of cognitive neuroscientists." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082380 TI - Daniel M. Wegner: Award for Distinguished Scientific Contributions. AB - Presents Daniel M. Wegner, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Contributions. "For seminal contributions that span psychology's breadth--from cognitive to social to personality to clinical--and that reach beyond its borders to philosophy and neuroscience. Daniel M. Wegner's studies on transactive memory, action identification, ironic processes, and apparent mental causation all bear his characteristic mark: a beautiful idea brought to life by an elegant experiment. He has spent his scientific career identifying new and important problems and then offering solutions that sparkle with originality and insight. He has seen doors where others saw walls, opened them to reveal new rooms, and illuminated their dark corners." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082381 TI - Setting free the bears: escape from thought suppression. AB - A person who is asked to think aloud while trying not to think about a white bear will typically mention the bear once a minute. So how can people suppress unwanted thoughts? This article examines a series of indirect thought suppression techniques and therapies that have been explored for their efficacy as remedies for unwanted thoughts of all kinds and that offer some potential as means for effective suppression. The strategies that have some promise include focused distraction, stress and load avoidance, thought postponement, exposure and paradoxical approaches, acceptance and commitment, meditation, mindfulness, focused breathing, attention training, self-affirmation, hypnosis, and disclosure and writing. Many of these strategies entail thinking about and accepting unwanted thoughts rather than suppressing them--and so, setting free the bears. (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082383 TI - Alan E. Kazdin: Award for Distinguished Scientific Applications of Psychology. AB - Presents Alan E. Kazdin, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Applications of Psychology. "For outstanding and pathbreaking contributions to the understanding of the development, assessment, and treatment of psychopathology. Alan E. Kazdin's theoretically innovative, methodologically rigorous, and scientifically informed research has significantly advanced knowledge of child and adolescent psychopathologies such as depression and conduct problems. His writings on research strategies and methods have set a high standard for rigor in the field. His work and his ideas have had an enormous impact on the science, practice, and teaching of psychology, and his research has strengthened assessment and treatment of children and adolescents in scientific and clinical settings. His passion, energy, wisdom, and wit have inspired countless colleagues and students over the years, and his work will no doubt continue to do so for many generations to come." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082384 TI - Evidence-based treatment research: Advances, limitations, and next steps. AB - This article highlights the development of evidence-based treatments (EBTs), the accomplishment their development reflects, and the limitations of current variations as a way of providing mental health services and care. Rather than review EBTs, I use the occasion to provide an overview of my work on the development of treatments for children referred clinically for aggressive and antisocial behavior. This work reflects a larger genre of intervention research that has developed treatments for a variety of disorders. After years of research and a healthy list of EBTs, where are we and where do we need to be? It is still the case that most people in need of services do not receive them, and disparities in providing services remain enormous. The vast majority of therapies, whether evidence based or not, use a model of delivery (one-to-one in person treatment) that is inherently limited as a way of reaching the large swath of people in need of services. Multiple models of delivery of treatment are needed. The article underscores the importance of developing these models of delivery and optimizing that development by understanding better the mechanisms of therapeutic change. (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082386 TI - Nicholas Epley: Award for Distinguished Scientific Early Career Contributions to Psychology. AB - Presents Nicholas Epley, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For brilliant empirical and theoretical contributions to social cognition in general and for creative insights into how people understand the minds of others in particular. Nicholas Epley's empirical work demonstrates how basic mechanisms of social cognition can lead to interpersonal conflict and misunderstanding. His theoretical work expands social cognition beyond its traditional focus on human beings as targets of judgment, showing how basic mechanisms explain people's understanding of minds of all kinds, from pets to gadgets to gods. His work shows how social psychology, at its best, increases understanding of everyday life and inspires others to understand more." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082387 TI - Adam M. Grant: Award for Distinguished Scientific Early Career Contributions to Psychology. AB - Presents Adam M. Grant, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For extensive, elegant, and programmatic research on the power of relational job design in enhancing employee motivation, productivity, and satisfaction; for creative and rigorous studies documenting the profound and surprising effects of connecting employees to their impact on others; for highlighting prosocial motivation, not only extrinsic and intrinsic motivations, as a key force behind employee behavior; and for demonstrating by example the feasibility and benefits of conducting field experiments, yielding studies rich in internal validity, external validity, and practical impact. In addition to his accomplishments, Adam M. Grant is known for his generosity as a scholar, teacher, and colleague." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082388 TI - Wendy Johnson: Award for Distinguished Scientific Early Career Contributions to Psychology. AB - Presents Wendy Johnson, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For innovative research explicating the nature, origin, and consequences of individual differences in intelligence and personality. With methodological rigor and theoretical incisiveness, Wendy Johnson has addressed some of the most vexing questions in the psychology of individual differences. She has shown how genetic and environmental factors jointly influence many important life outcomes, explicated the structure of cognitive abilities, and demonstrated how cognitive ability and personality contribute to gender differences in academic achievement. Her consummate mastery of research methodology, genetics, personality theory, and human abilities has enabled her to advance an integrative program of research that is having a fundamental impact on the field." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082389 TI - Cindy Lustig: Award for Distinguished Scientific Early Career Contributions to Psychology. AB - Presents Cindy Lustig, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "Cindy Lustig has made groundbreaking contributions to the study of attention and memory. She has contributed to our understanding of the role of interference in implicit memory and of the neural underpinnings of age differences in cognition as well as to a developing literature on effective interventions to boost cognitive functioning. Her methods include a genetic approach to understanding variability in cognitive functioning in old age as well as the use of animal models. Her work has been widely cited and hailed for its innovative methods and findings." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082390 TI - David Melcher: Award for Distinguished Scientific Early Career Contributions to Psychology. AB - Presents David Melcher, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For his elegant and groundbreaking work on one of the most important problems in perceptual psychology, the transfer of perceptual representations across eye movements. David Melcher's innovative experiments used perceptual aftereffects to show how remapping of visual locations underlies the creation of the percept of a clear and stable world. His work on the accumulation of memory contributed importantly to the understanding of natural perceptual representations and their neural underpinnings. His elegant reviews of transsaccadic perception communicated to a broad audience the remarkable capacity of the brain to create seamless perceptual representations despite the disruptions produced by eye movements." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082393 TI - Roxane Cohen Silver: Award for Distinguished Senior Career Contributions to Psychology in the Public Interest. AB - Presents Roxane Cohen Silver, the 2011 winner of the American Psychological Association Award for Distinguished Senior Career Contributions to Psychology in the Public Interest. "Roxane Cohen Silver is an internationally known expert in psychological responses to trauma. Her exceptional research has examined adjustment to an array of crises, including sudden loss, war, natural disasters, community violence, and the 9/11 attacks. As an advisor to the U.S. Department of Homeland Security and in testimony to Congress, she has shaped policy concerning psychosocial dimensions of disaster preparedness and response. Through her service on the Board of Directors of Psychology Beyond Borders, she has addressed community health effects of terror and disasters. Her warmth, humor, and scholarship are truly inspiring, and she embodies the values this award was created to honor." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082394 TI - Edward A. Delgado-Romero: Award for Distinguished Early Career Contributions to Psychology in the Public Interest. AB - Presents Edward A. Delgado-Romero, the 2011 winner of the American Psychological Association Award for Distinguished Early Career Contributions to Psychology in the Public Interest. "Societies, professions, and individual citizens are enriched by the contributions of those who care. Edward A. Delgado-Romero has demonstrated through his scholarship, leadership in psychological associations such as the National Latina/Latino Psychological Association, and collaborations with universities and school districts in Georgia that he cares and is committed to addressing challenges in the provision of culturally sensitive psychological services to benefit the public interest. His example of servant leadership leaves a legacy to other early career professionals and graduate students alike. Es un hijo honorado." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082396 TI - Richard Rogers: Award for Distinguished Contributions to Research in Public Policy. AB - Presents Richard Rogers as the 2001 winner of the American Psychological Association Award for Distinguished Contributions to Research in Public Policy. "Richard Rogers casts a long shadow over the realm of psychological research with public policy implications. His achievements concerning criminal responsibility and malingering have been important and lasting, but his most uniquely impactful contribution to public policy is his enhancement of our understanding of the constitutional protections embodied in Miranda rights. His investigations have exploded the myth of a single, easily understood Miranda warning. The ramifications of this work are profound, especially for socially marginalized populations, and include its direct acknowledgment as the impetus for critical developments in American Bar Association policy on custodial interrogations." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082397 TI - Getting it wrong about Miranda rights: false beliefs, impaired reasoning, and professional neglect. AB - Television and other media inundate Americans with innumerable yet fragmentary examples of Miranda warnings; however, familiarity born of repeated exposures cannot be equated with accuracy or understanding. The intended purpose of these warnings is to inform and caution rather than to pacify and reassure--a purpose that cannot be realized when most custodial suspects assume that they already know everything the law insists they should be told. Painstakingly negotiated Constitutional safeguards are further imperiled when attorneys, judges, and forensic evaluators are lulled into complacency by the commonly held misconception that everyone understands their Miranda rights. This article elucidates certain false beliefs and misapprehensions regarding Miranda comprehension and identifies widespread neglect of these issues by the professional community. (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082400 TI - Jon Carlson: Award for Distinguished Career Contributions to Education and Training in Psychology. AB - Presents Jon Carlson as the 2011 winner of the American Psychological Association Award for Distinguished Career Contributions to Education and Training in Psychology. "For his contributions in creating educational and training materials in psychology for instruction and the public. Jon Carlson has a distinguished career in higher education, maintained an active private practice, served 34 years as a school psychologist/counselor, is a prolific author and scholar, and is an innovator in the development of media-based training materials. His contribution to education and training is noteworthy for the volume of his professional production, the scope of topics addressed, and his ability to provide meaningful tools to change how psychologists are trained. His audiovisual work documents the profession of psychology in terms of research and practice for current scholars and for future generations." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082402 TI - Arthur C. Graesser: Award for Distinguished Contributions of Applications of Psychology to Education and Training. AB - Presents Arthur C. Graesser as the 2011 winner of the American Psychological Association Award for Distinguished Contributions of Applications of Psychology to Education and Training. "As a multifaceted psychologist, cognitive engineer of useful education and training technologies, and mentor of new talent for the world of applied and translational cognitive science, Arthur C. Graesser is the perfect role model, showing how a strong scholar and intellect can shape both research and practice. His work is a mix of top-tier scholarship in psychology, education, intelligent systems, and computational linguistics. He combines cognitive science excellence with bold use of psychological knowledge and intelligent systems to design new generations of learning opportunities and to help lay the foundation for a translational science of learning." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082403 TI - Learning, thinking, and emoting with discourse technologies. AB - This is an unusual moment in the history of psychology because of landmark advances in digital information technologies, computational linguistics, and other fields that use the computer to analyze language, discourse, and behavior. The technologies developed from this interdisciplinary fusion are helping students learn and think in ways that are sensitive to their cognitive and emotional states. Recent projects have developed computer technologies that help us understand the nature of conversational discourse and text comprehension in addition to improving learning. AutoTutor and other systems with conversational agents (i.e., talking heads) help students learn by holding conversations in natural language. One version of AutoTutor is sensitive to the emotions of students in addition to their cognitive states. Coh-Metrix analyzes texts on multiple levels of language and discourse, such as text genre, cohesion, syntax, and word characteristics. Coh-Metrix can assist students, teachers, principals, and policymakers when they make decisions on the right text to assign to the right student at the right time. Computers are not perfect conversation partners and comprehenders of text, but the current systems are undeniably useful. (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082405 TI - Michael K. Scullin: Psi Chi/APA Edwin B. Newman Graduate Research Award. AB - Presents Michael K. Scullin as the 2011 winner of the American Psychological Association Psi Chi/APA Edwin B. Newman Graduate Research Award. "For an outstanding research paper that examines the relationship between prospective memory in executing a goal and various lapses of time from 20 minutes up to a 12- hour wake delay and a 12-hour sleep delay. The results suggest that consolidation processes active during sleep increase the probability of goal execution. The paper, titled 'Remembering to Execute a Goal: Sleep On It!' was published in Psychological Science in 2010 and was the basis for Michael K. Scullin's selection as the recipient of the 2011 Psi Chi/APA Edwin B. Newman Graduate Research Award. Mark A. McDaniel, PhD, served as faculty research advisor." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082408 TI - Ronald F. Levant: Award for Distinguished Professional Contributions to Applied Research. AB - Presents Ronald F. Levant as the 2011 winner of the American Psychological Association Award for Distinguished Professional Contributions to Applied Research. "Ronald F. Levant is one of the world's leading authorities on the psychology of men and masculinity. Through his pioneering research, he helped define gender role strain theory, fostered a multicultural understanding of fathering and masculinity issues, and developed and evaluated the Male Role Norms Inventory and the Normative Male Alexithymia Scale. He also established the empirical foundation for the normative male alexithymia hypothesis, which proposes that male socialization inhibits emotional expression in males, and he developed alexithymia reduction treatment, which is designed to prepare men to engage more fully in psychotherapy and to experience greater benefit from it." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082409 TI - Research in the psychology of men and masculinity using the gender role strain paradigm as a framework. AB - This article introduces the specialty area of the psychology of men and masculinity to the broader community of American psychologists, focusing on research conducted using the gender role strain paradigm. The review covers the rationale for and aims of the psychology of men and masculinity and the gender role strain paradigm. It provides an extensive discussion of masculinity ideologies--the core construct in the strain paradigm--including the definition of masculinity ideology and considerations of masculinity ideology versus masculinity ideologies, traditional masculinity ideology, the measurement of masculinity ideologies, the Male Role Norms Inventory-Revised, women's and adolescent's masculinity ideologies, and conformity to masculine norms. It then takes up the 3 types of masculine gender role strain (discrepancy, dysfunction, and trauma) and the normative male alexithymia hypothesis. Finally, it considers future research directions. (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082411 TI - Antonio E. Puente: Award for Distinguished Professional Contributions to Independent Practice. AB - Presents Antonio E. Puente as the 2011 winner of the American Psychological Association Award for Distinguished Professional Contributions to Independent Practice. "For his decades of efforts to enhance the recognition of psychologists in providing health care services, through his work with the Current Procedural Terminology (CPT) Panel to develop and maintain appropriate CPT codes for the breadth of professional practice; for his willingness to participate in litigation establishing the expertise of neuropsychologists to testify in court about their findings; for his tireless work in cross-cultural assessment relative to criminal trials; for his leadership of professional societies in clinical neuropsychology; for his promotion of legislation and policy at all levels of government; and for his countless other contributions to the enhancement of independent practice in psychology. Antonio Puente is a far-thinking visionary who freely shares his knowledge to improve the quality of psychological practice and the reimbursement system that attests to the worth of the profession. He is the very embodiment of the psychologist for whom this award is intended." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082412 TI - Psychology as a health care profession. AB - This article reviews the concept that professional psychology is synonymous with mental health. The acceptance of this concept results in limiting the potential impact that psychology has for both individuals and society. Historical antecedents of both psychology and professional psychology are considered as laying a foundation for a necessary paradigm shift from primarily mental health to health. Clinical neuropsychology, health psychology, and prescriptive authority are considered as three examples that may assist in guiding professional psychology toward inclusiveness into a broader health care arena. Limitations of the proposed paradigm and directions for its future are considered. (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082414 TI - Ronald H. Rozensky: Award for Distinguished Professional Contributions to Institutional Practice. AB - Presents Ronald H. Rozensky, the 2011 winner of the American Psychological Association Award for Distinguished Professional Contributions to Institutional Practice. "For his dedication and distinguished contributions to excellence in institutional practice through creative leadership in education, training, and patient care. Ronald H. Rozensky's accomplishments include serving as the founding editor of the Journal of Clinical Psychology in Medical Settings, contributing to federal health care policy recommendations while serving as chairperson of a Health Resources and Services Administration health care advisory committee, and working on regulatory changes made while representing APA on the Joint Commission on the Accreditation of Healthcare Organizations. A tireless champion of institutional practice while serving on APA's Board of Directors and as chairperson of the Boards of Educational and Professional Affairs and the Commission for the Recognition of Specialties and Proficiencies in Professional Psychology, he is a dynamic advocate for psychology's administrative independence in all settings and its interprofessional focus in health care." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082415 TI - The institution of the institutional practice of psychology: health care reform and psychology's future workforce. AB - Implications for the future of professional psychology are discussed and related to the Patient Protection and Affordable Care Act, patient-centered health care homes and accountable care organizations, and the growing importance of interprofessional competencies in health care. The need for increased information about the psychology workforce is related to the history of the institutional practice of psychology and how that data must be used to plan for the supply of psychologists required to meet the service demands of the changing health care system. Several challenges to the field of psychology are offered, along with steps that must be taken by the profession to prepare for increased institutionally based health care services in the future. (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082417 TI - Jordan M. Braciszewski: APA/APAGS Award for Distinguished Graduate Student in Professional Psychology. AB - Presents Jordan M. Braciszewski as the 2011 winner of the American psychological Association APA/APAGS Award for Distinguished Graduate Student in Professional Psychology. "For his concerted efforts to identify the needs of homeless and other at-risk populations and to design and provide necessary services for them. Jordan M. Braciszewski is committed to using applied psychological science and evidence-based intervention methods to assist the most disadvantaged in our society. He has already provided additions to the relevant research literature and has volunteered countless hours of his time to implement community-based interventions and provide direct services himself. He has sought out the training experiences necessary to assist him in doing an even better job in the future in these public service activities." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082419 TI - Dan Olweus: Award for Distinguished Contributions to the International Advancement of Psychology. AB - Presents Dan Olweus, the 2011 winner for the American Psychological Association Award for Distinguished Contributions to the International Advancement of Psychology. "For his lifelong commitment to understand bullying among children and create safe and humane school settings. Dan Olweus led the education of the global public about the nature and prevalence of bullying, its often serious consequences, and the behavior of adults that allows bullying to occur. He has done so as a careful researcher, a thoughtful theoretician, a creative program developer, and a tireless advocate. He uncovered the problem and created and evaluated a comprehensive solution. Throughout his career, he has been guided by a concern for careful psychological inquiry and a commitment to the promotion of human rights." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID- 22082420 TI - Headaches and academic performance in university students: a cross-sectional study. AB - OBJECTIVES: To estimate the 1-year prevalence of headache, its repercussion and its association with the academic performance of university students. METHODS: Cross-sectional study. Three hundred eighty students were randomly selected out of the 1718, 90.5% of them were interviewed. A semi-structured interview, the Headache Impact Test (HIT-6) and the Hospital Anxiety and Depression Scale were used. The variables related to academic performance: absenteeism, performance coefficient and number of failures in disciplines, were obtained by consulting the academic records. RESULTS: Three hundred forty-four students were interviewed. The headache prevalence was 87.2%. Migraine prevalence was 48.5%. Tension-type headache prevalence was 42.4%. During the 3 months prior to the interview, 8.7% sought emergency services, 30.8% missed class, and 30.8% had a reduction in their productive capacity because of headache. HIT-6: substantial/severe impact = 49%. Multiple linear regressions have shown that serious/very serious-impact headaches are significantly related to greater number of discipline failure and absenteeism. There was no association between student grades and headaches. CONCLUSION: A high prevalence of headache in the studied population was verified. A high headache impact on a student's life was associated with worse academic performance. PMID- 22082421 TI - Increase of capsaicin-induced trigeminal Fos-like immunoreactivity by 5-HT(7) receptors. AB - OBJECTIVE: To explore whether pharmacological stimulation of the 5 hydroxytryptamine(7) (5-HT(7) ) receptor modulates Fos-like immunoreactivity in the trigeminal nucleus caudalis of rats. BACKGROUND: The serotonin 5-HT(7) receptor was proposed to be involved in migraine pathogenesis and evidence suggests it plays a role in peripheral nociception and hyperalgesia through an action on sensory afferent neurons. METHODS: The potential activating or sensitizing role of 5-HT(7) receptors on trigeminal sensory neurons, as visualized by Fos-like immunoreactivity in the superficial layers of the trigeminal nucleus caudalis in rats, was investigated using the 5-HT(7) receptor agonist, LP-211, in the absence and the presence of intracisternal capsaicin, respectively. The agonist effect was characterized with the 5-HT(7) receptor antagonist, SB-656104. Male Wistar rats received a subcutaneous injection of LP 211, SB-656104, and SB-656104 + LP-211. They were then anesthetized and prepared to receive an intracisternal injection of capsaicin or its vehicle. Animals were perfused and brains removed; sections of the brain stem from the area postrema to the CI level were obtained and processed for Fos immunohistochemistry. RESULTS: Capsaicin but not its vehicle induced Fos-like immunoreactivity within laminae I and II of trigeminal nucleus caudalis. Pretreatment with LP-211 had no effect on Fos-like immunoreactivity but strongly increased the response produced by capsaicin; this effect was abolished by SB-656104. Interestingly, capsaicin induced Fos-like immunoreactivity was abolished by SB-656104 pretreatment thus suggesting involvement of endogenous 5-HT. CONCLUSIONS: Data suggest that 5-HT(7) receptors increase activation of meningeal trigeminovascular afferents and/or transmission of nociceptive information in the brain stem. This mechanism could be relevant in migraine and its prophylactic treatment. PMID- 22082422 TI - Photoreactivity of the occipital cortex measured by functional magnetic resonance imaging-blood oxygenation level dependent in migraine patients and healthy volunteers: pathophysiological implications. AB - BACKGROUND: The brain of migraineurs is hyperexcitable, particularly the occipital cortex, which is probably hypersensitive to light. Photophobia or hypersensitivity to light may be accounted for by an increased excitability of trigeminal, the visual pathways, and the occipital cortex. OBJECTIVE: To study light sensitivity and photophobia by assessing the response to light stimuli with functional magnetic resonance imaging-blood oxygenation level dependent (fMRI BOLD) of the occipital cortex in migraineurs and in controls. Also, to try to decipher the contribution of the occipital cortex to photophobia and whether the cortical reactivity of migraineurs may be part of a constitutional (defensive) mechanism or represents an acquired (sensitization) phenomenon. METHODS: Nineteen patients with migraine (7 with aura and 12 without aura) and 19 controls were studied with fMRI-BOLD during 4 increasing light intensities. Eight axial image sections of 0.5 cm that covered the occipital cortex were acquired for each intensity. We measured the extension and the intensity of activation for every light stimuli. Photophobia was estimated according to a 0 to 3 semiquantitative scale of light discomfort. RESULTS: Migraineurs had a significantly higher number of fMRI-activated voxels at low (320.4 for migraineurs [SD = 253.9] and 164.3 for controls [SD = 102.7], P = .027) and medium-low luminance levels (501.2 for migraineurs [SD = 279.5] and 331.1 for controls [SD = 194.3], P = .034) but not at medium-high (579.5 for migraineurs [SD = 201.4] and 510.2 for controls [SD = 239.5], P = .410) and high light stimuli (496.2 for migraineurs [SD = 216.2] and 394.7 for controls [SD = 240], P = .210). No differences were found with respect to the voxel activation intensity (amplitude of the BOLD wave) between migraineurs and controls (8.98 [SD = 2.58] vs 7.99 [SD = 2.57], P = .25; 10.82 [SD = 3.27] vs 9.81 [SD = 3.19], P = .31; 11.90 [SD = 3.18] vs 11.06 [SD = 2.56], P = .62; 11.45 [SD = 2.65] vs 10.25 [SD = 2.22], P = .16). Light discomfort was higher in the group of migraineurs at all the intensities tested, but there was no correlation with the number of activated voxels in the occipital cortex and photophobia. Repetitive light stimuli failed to demonstrate a lack of habituation in migraineurs. CONCLUSIONS: Migraineurs during interictal periods showed hyperxcitability of the visual cortex with a wider photoresponsive area, the underlying mechanism probably being dual: constitutional-defensive and acquired sensitizating. PMID- 22082423 TI - Acute striatal necrosis in hemiplegic migraine with de novo CACNA1A mutation. AB - We report the case of a 9-year-old girl with early-onset developmental delay, chronic ataxia and prolonged hemiplegic migraine episodes bringing about progressive deterioration. Two days into one episode, diffusion-weighted magnetic resonance imaging disclosed unilateral striatal abnormal signal consistent with cytotoxic edema, which evolved into atrophy on follow-up scans. Mutational screen of CACNA1A gene identified a de novo p.Tyr1387Cys mutation. PMID- 22082424 TI - Sumatriptan in excessive doses over 15 years in a patient with chronic cluster headache. AB - We report the case of a 49-year-old lady with cluster headache, who had received sumatriptan s.c. treatment for 15 years with daily dosages between 12 and 222 mg (average of 150 mg during the last year). The therapy was successful in aborting CH attacks. Long-term overdosage of sumatriptan was well tolerated, without adverse events. PMID- 22082425 TI - Bruxism, temporomandibular dysfunction, tension type headache, and migraine: a comment. PMID- 22082426 TI - Pathophysiology of chronic migraine and mode of action of preventive medications: a comment. PMID- 22082428 TI - Botulinum toxin and the treatment of headache: a clinical review. PMID- 22082430 TI - Chronic migraine: a road less travelled. PMID- 22082429 TI - Insights into the mechanism of onabotulinumtoxinA in chronic migraine. AB - OnabotulinumtoxinA has recently been approved by regulatory agencies in the UK and United States for treatment of chronic migraine based on data generated from the PREEMPT studies. As such, onabotulinumtoxinA is the only prophylactic therapy specifically approved for chronic migraine. Most headache clinicians would agree that acute episodic migraine and chronic migraine differ in their pathophysiology, etiology, diagnosis, and response to pharmacological as well as nonpharmacological therapies. Of the 7 botulinum neurotoxin serotypes, botulinum neurotoxin type A (onabotulinumtoxinA) has been the most thoroughly investigated in preclinical and clinical studies. Based on preclinical studies, onabotulinumtoxinA is known to inhibit the release of excitatory neurotransmitters from both motor and sensory neurons by preventing vesicle fusion to the cell membrane. In addition to the well-documented myorelaxant effects of this neurotoxin, onabotulinumtoxinA can exert a direct analgesic effect that likely involves inhibition of primary and secondary nociceptive neurons. The inhibitory effects of onabotulinumtoxinA are also likely to involve suppressing the activity of myogenic trigger points and decreasing the persistent nociceptive barrage that promotes and maintains central sensitization. This article describes possible mechanisms to explain how onabotulinumtoxinA functions as a therapy for chronic migraine and considers why treatment with the neurotoxin is not effective in some chronic migraineurs. PMID- 22082431 TI - Abuse and maltreatment: their effect on headache. PMID- 22082432 TI - The efficacy of acupressure at the Sanyinjiao point in the improvement of women's general health. AB - OBJECTIVES: This study's objective was to examine the effectiveness of Sanyinjiao point (SP6) acupressure on women's general health. DESIGN: This was a randomized, single-blind clinical trial. SETTING: The setting for this trial was at Medical University, Bojnoord University of Medical Science, Bojnoord, Iran. MATERIALS AND METHODS: Eighty-six (86) university students were recruited for this study. Their demographic characteristics were gathered before the intervention commenced. Participants completed General Health Questionnaires (GHQ) prior to participation. Next, they were randomly assigned to either the acupressure receiving group or the sham-pressure-receiving group. The study group received acupressure at the Sanyinjiao point, while the control group received sham pressure. OUTCOME MEASURES: Both groups completed GHQ after both the first and second months of intervention. Data analysis was carried out using SPSS version 13.5 for Windows. RESULTS: The mean age of those who completed the study was 20.84+/-1.64 years. Mean scores of GHQs were similar between groups before intervention (p>0.05). The general health of participants in both groups improved after intervention, and the amelioration in four domains was significant in the groups (p<0.05 within group). It was found that acupressure was more effective than sham pressure. In addition, there was a statistically significant difference between the two groups in the four domains of their general heath after the first month of the intervention (p<0.0001). Furthermore, the general health status of the participants changed much more after the second month in both the acupressure intervention and the sham pressure groups; nevertheless, acupressure was more effective than sham pressure (p<0.05). CONCLUSIONS: Both acupressure and sham pressure were effective in promoting women's general health; nevertheless, the efficacy of acupressure was more than that of sham pressure. SP6 acupressure could be regarded as a self-manageable approach to improve women's general health. PMID- 22082433 TI - The relationship between dental occlusion/temporomandibular joint status and general body health: part 2. Fascial connection of TMJ with other parts of the body. AB - In part 1 of this study, it was discussed that dental occlusion/temporomandibular joint (TMJ) status is functionally connected to general body health. The purpose of this part of the study was to attempt to formulate a conceptual account, the "fascial connection theory for TMJ and other parts of the body," to explain the functional connection between TMJ and other parts of the body. The first hypothesis that was studied is that TMJ and other parts of body are connected through the fascia as asserted by the myofascial-release schools, and the second one is that they are connected through the meridian system constituted of fascia (connective tissue). The fascial connection theory proposed here can explain the functional connection between dental occlusion/TMJ and other parts of the body based on either myofascial release or the qi and meridian system, or a combination of the two. Therefore, dental occlusion should be built up and maintained in a normal natural condition, and causes of deterioration of TMJ status should be treated in an effort to restore the natural condition. Other possible mechanisms that can account for these connections require elucidation, and additional experimental investigation should be undertaken. PMID- 22082438 TI - Sporting activity following colic surgery in horses: a retrospective study. AB - REASONS FOR PERFORMING STUDY: There is a paucity of studies addressing sporting activity and horse owners' satisfaction after horses have undergone colic surgery. OBJECTIVES: To determine 1) survival rate after colic surgery, 2) prevalence of horses returning to, or starting, sporting activities and 3) assess the owners' satisfaction regarding colic surgery. METHODS: Cases that underwent exploratory celiotomy for colic between January 2005 and August 2010 were reviewed. All horses that had one or more celiotomies and were discharged after colic surgery were included in a telephone questionnaire survey. Only horses that survived at least 6 months after colic surgery were included in the sporting activity analysis. Data extracted from the records included case details, intra operative diagnosis and surgical treatment. Information from a telephone questionnaire included the horses' post surgical details (horse alive or subjected to euthanasia, post operative complications, pre- and post surgical use, return to sporting activity, sporting performance, behavioural changes, management changes and recommendation by owner for colic surgery). A logistic regression model was used for the statistical analysis of post hospitalisation performance and an ordinal regression model used for analysis of post colic complications and of owner's recommendation of surgery. A Kaplan-Meier survival curve was computed to show survival of horses discharged after colic surgery. RESULTS: The survival rates (%) at 6, 12, 24, 36, 48 and 60 months were 95.3, 86.6, 80.9, 76.9, 62.1 and 57.6, respectively. A large majority of horses (86.1%) resumed or started sporting activities after colic surgery. The proportion of horses that the owners believed to achieve the same or better performance after surgery was 83.5%. In 89.9% of the cases, owners stated that they would recommend colic surgery. CONCLUSIONS: Horses discharged after colic surgery had a high long term survival rate. A high prevalence of horses resumed or started sporting activities with a high proportion of horses at their presurgical performance level. The large majority of owners of discharged horses were satisfied with colic surgery performed on their horses. PMID- 22082439 TI - Incidence of support limb laminitis in horses treated with half limb, full limb or transfixation pin casts: a retrospective study of 113 horses (2000-2009). AB - REASONS FOR PERFORMING STUDY: To determine the incidence of support limb laminitis among horses treated with half limb, full limb or transfixation pin casts and determine potential risk factors. METHODS: Medical records of 113 horses treated with half limb, full limb or transfixation pin casts at an equine referral hospital from 2000 to 2009 were reviewed. Associations between potential risk factors and development of support limb laminitis were evaluated by bivariable and multivariable logistic regression analyses. RESULTS: Of the 113 horses that received casts, 14 (12%) developed confirmed support limb laminitis. The bodyweight of the horse and duration of casting in weeks were significantly associated with support limb laminitis. Horses requiring full limb casts or transfixation pin casts were more likely to develop this complication than horses requiring half limb casts. There were no significant associations between developing support limb laminitis and weightbearing capacity on presentation to the hospital, the limb affected (fore- or hind), whether there was a fracture present or breed of horse. CONCLUSIONS: Support limb laminitis is a relatively common complication among horses treated with half limb, full limb and transfixation pin casts. Greater durations of casting and higher bodyweights increase the likelihood of developing this complication. POTENTIAL RELEVANCE: Support limb laminitis may occur secondary to any painful unilateral lameness and is not necessarily more likely to develop in horses with severe orthopaedic conditions such as fractures. However, heavier horses, those requiring casts for longer periods of time and those that require a full limb or transfixation pin cast as opposed to a half limb cast should be considered to have an increased risk for developing support limb laminitis post operatively. PMID- 22082440 TI - Phenylbutazone and flunixin meglumine used singly or in combination in experimental lameness in horses. AB - REASON FOR PERFORMING STUDY: Using an adjustable heart bar shoe model of foot pain, the objective of this study was to test the hypothesis that the combined use of phenylbutazone (PBZ) and flunixin meglumine (FM) would prove more efficacious in alleviating lameness than either drug alone. MATERIALS AND METHODS: One hour after induction of lameness at weekly intervals, 8 healthy adult Thoroughbred horses randomly underwent one of 4 i.v. treatments: saline (SAL) placebo (1 ml/45 kg bwt), PBZ (4.4 mg/kg bwt), FM (1.1 mg/kg bwt) or PBZ+FM (at the same dosages as given individually). Heart rate (HR) and lameness score (LS) responses were assessed in a blinded manner every 20 min for 5 h after lameness induction and then hourly for 12 h after treatment. Jugular venous blood samples were obtained at -1, 0, 0.05, 1, 2, 4, 6, 8, 10 and 12 h and subsequently analysed for drug concentrations. Repeated measures ANOVA and post hoc Tukey's test were used to identify analgesic effects at a significance level of P<0.05. RESULTS: Heart rate was lower in all nonsteroidal anti-inflammatory drug (NSAID) treated trials from 2 h to 10 h post treatment (P<0.05). Analgesic effects of FM and PBZ+FM, as evidenced by decreases in HR, lasted for 12 h post treatment (P<0.05). Lameness score decreased earlier in PBZ and PBZ+FM trials than in FM trials (P<0.05) and the analgesic effect on LS lasted for 12 h post treatment for all NSAID trials (P<0.05). Peak PBZ plasma concentration was 73.7 +/- 6.0 and 77.9 +/- 5.5 ug/ml. Peak FM concentration was 12.0 +/- 0.8 and 13.7 +/- 1.0 ug/ml. CONCLUSIONS: It was concluded that the combination of PBZ+FM was not more effective than either PBZ or FM alone. These data do not support the hypothesis that the combination is more efficacious at these dosages than either drug alone in this model of acute foot pain. PMID- 22082441 TI - Dynamic respiratory videoendoscopy in ridden sport horses: effect of head flexion, riding and airway inflammation in 129 cases. AB - REASONS FOR PERFORMING STUDY: Dynamic upper airway obstruction (UAO) is a cause of respiratory noise and sometimes poor performance in sport horses. Riding, head flexion and airway inflammation may impact upper respiratory tract stability during exercise. OBJECTIVES: To evaluate upper airway mechanical behaviour in ridden sport horses using overground endoscopy and the effect of head flexion, rider intervention and underlying airway inflammation on the pharynx and larynx. METHODS: Resting and exercising videoendoscopic recordings during ridden exercise were obtained in 129 sport horses referred mainly for respiratory noise, poor performance or routine evaluation. The rider modified poll flexion and way of riding during the test and associated changes in UAO were recorded. Presence of upper and lower airway inflammation was also assessed. RESULTS: Dynamic UAO was diagnosed in 91% (64/70) of the horses referred for respiratory noise and in 71% (29/41) of horses referred for poor performance. Pharyngeal instability was the most frequently diagnosed problem. However, differences were observed between dressage horses and showjumpers. Rider interaction and head flexion exacerbated upper airway instability and promoted the occurrence of complex UAO. Both lower airway inflammation and pharyngeal lymphoid hyperplasia were associated with pharyngeal instability, but not with any other UAO. CONCLUSIONS: Rider intervention during ridden exercise (i.e. the various movements a horse might be asked to perform) influences upper airway morphology and function and, in cases of upper airway dynamic obstruction, can contribute to increasing laryngeal and/or pharyngeal instability in sport horses. POTENTIAL RELEVANCE: As these are changes that would not usually be seen with treadmill videoendoscopy, ridden videoendoscopy should be the preferred method for evaluation of the upper airway in sport horses. PMID- 22082442 TI - Adaptation and validation of a bacteria-specific enzyme-linked immunosorbent assay for determination of farm-specific Lawsonia intracellularis seroprevalence in central Kentucky Thoroughbreds. AB - REASONS FOR PERFORMING STUDY: Lawsonia intracellularis is the causative agent of equine proliferative enteropathy (EPE), a disease for which no large-scale seroprevalence studies have been conducted. OBJECTIVES: To validate and use an equine-specific enzyme-linked immunosorbent assay (ELISA) for L. intracellularis to determine the seroprevalence of L. intracellularis on numerous farms. METHODS: An ELISA, in which purified antigen was used, was adapted from previous work in swine. A total of 337 Thoroughbreds from 25 central Kentucky farms were enrolled and monthly serum samples collected from August 2010 to January/February 2011. Samples were screened for L. intracellularis-specific antibodies using a modified ELISA. Farms were classified into one of 3 groups based on 3 year prior history with EPE. RESULTS: The ELISA intra-assay coefficient of variation (CV) was 6.73 and inter-assay CV was 9.60. An overall seroprevalence of 68% was obtained, with farm-specific seroprevalances ranging from 14 to 100%. A significant difference was found in the average seroprevalence (P<0.05) on farms with a confirmed recent history of EPE cases. Additionally, both lower average ELISA unit (EU) values (P = 0.079) and maximum EU values (P = 0.056) were detected on farms with no recent EPE history when compared to the other groups. A bimodal exposure distribution to L. intracellularis was detected in the fall and winter months. CONCLUSIONS: Recent history of EPE was associated with higher average seroprevalence indicating increased exposure on farms with prior cases of EPE. Seasonally bimodal exposure was also observed. POTENTIAL RELEVANCE: The adapted ELISA appears to be useful for determination of L. intracellularis-specific antibody levels. The high farm-specific seroprevalences and bimodal distribution of exposure to L. intracellularis were unexpected and suggest that farms with a previous history of EPE remain at risk due to heightened exposure levels beyond early winter. PMID- 22082443 TI - Efficacy of human chorionic gonadotropin to induce ovulation in the mare, when associated with a single dose of dexamethasone administered at breeding time. AB - REASONS FOR PERFORMING STUDY: Human chorionic gonadotropin (hCG) and dexamethasone have a role in the reproductive management protocols of mares susceptible to persistent mating-induced endometritis (PMIE). However, it is possible that there is interference between these 2 drugs. OBJECTIVES: The objective of this retrospective study was to determine the efficacy of hCG to induce ovulation in mares treated with dexamethasone at breeding time. METHODS: Medical records from 152 mares and 223 cycles were analysed. In 113 cycles, mares susceptible to PMIE were treated with 1500 iu hCG and a single dose of 50 mg dexamethasone, 110 cycles were used as controls and subsequent ovulation was assessed ultrasonographically and compared. RESULTS: Dexamethasone did not inhibit ovulation in mares susceptible to PMIE. CONCLUSIONS AND POTENTIAL RELEVANCE: Multiple administrations of dexamethasone to mares in early oestrus have induced ovulation failure. However, a single dose of dexamethasone, administered at breeding time, has been used as an effective modulator of PMIE in susceptible mares and does not interfere with efficacy of hCG to induce ovulation. PMID- 22082444 TI - Sperm selection using single layer centrifugation prior to cryopreservation can increase thawed sperm quality in stallions. AB - REASONS FOR PERFORMING STUDY: The increasing use of modern reproductive techniques in human medicine has led to a higher demand for isolation of motile sperm. Several of these isolation techniques have been adapted for veterinary use and can be applied for the selection of a superior sperm sample from stallion semen. Until recently a major disadvantage of such isolation techniques was the limitation in sperm volume that could be handled. Androcoll-E had been shown to be successful for processing large volumes of equine semen but there are few data to substantiate the potential beneficial effect of freezing an Androcoll-E selected equine sperm sample to obtain higher quality following thawing. OBJECTIVES AND METHODS: In this study, the effect of Androcoll-E treatment of sperm prior to cryopreservation was compared with cushioned centrifugation using ejaculates from 8 different stallions selected because they were known to have semen of differing quality following freezing. RESULTS: Androcoll-E treatment increased measures of semen quality prior to freezing. However, Androcoll-E treatment reduced the yield of sperm following centrifugation when compared with the cushion centrifuged control group (50.9 +/- 14.2% vs. 97.1 +/- 9.0%, respectively). Quality analysis following thawing showed an overall improved sperm quality for Androcoll-E treated samples and average post thaw progressive motility (PM) was 41.6% compared with 30.5% for the cushion centrifuged group. CONCLUSIONS AND POTENTIAL RELEVANCE: Androcoll-E can be used with good results to select a superior sperm population prior to cryopreservation, in order to produce good-quality frozen thawed semen. PMID- 22082445 TI - Nictitating membrane resection in the horse: a comparison of long-term outcomes using local vs. general anaesthesia. AB - REASONS FOR PERFORMING STUDY: Neoplasia, for which surgical excision is a frequent treatment, is the most common disease of the equine nictitating membrane. There is little long-term follow-up information available to the practitioner regarding the long-term effects of nictitating membrane excision on ocular health. No information is available to compare recurrence of primary neoplasia of the nictitating membrane after excision with local or general anaesthesia. OBJECTIVES: To evaluate the long-term complications of nictitating membrane resection in horses; recurrence of neoplasia of the nictitating membrane when nictitating membrane resection is performed under local vs. general anaesthesia and if the method of anaesthesia used to permit resection of the affected membrane influences the recurrence of neoplasia of the nictitating membrane after complete nictitating membrane resection. METHODS: Records of 26 horses receiving resection of the nictitating membrane for primary neoplasia of the nictitating membrane 1999-2009 were reviewed. Clinical examination findings, surgical procedure, anaesthesia type, histopathological findings and details of adjunctive treatment were recorded. Owners were contacted via telephone regarding post operative outcomes. Data were analysed using a Fisher's exact test (P<0.05). RESULTS: The most common long-term complication of nictitating membrane excision was mild ocular discharge. Squamous cell carcinoma was the most frequent histopathological diagnosis. Recurrence of neoplasia was uncommon (2/26 horses). No significant difference in the number of horses experiencing recurrence of neoplasia was detected between groups receiving general anaesthesia vs. those receiving local anaesthesia. CONCLUSIONS: Resection of the nictitating membrane in horses following local anaesthesia is not associated with increased risk of recurrence of neoplasia compared with excision under general anaesthesia. Resection of the nictitating membrane is not associated with any long-term ocular side effects and can be an effective modality for cure of primary neoplasia of the nictitating membrane in selected cases. PMID- 22082446 TI - In vitro comparison of three suture techniques for anastomosis of the equine small intestine. AB - REASONS FOR PERFORMING STUDY: The equine small intestine can be affected by a variety of disorders that may require some form of bypass or anastomosis. Many suture patterns have been used in equine anastomoses to minimise post operative complications, which include leakage from the anastomosis site, stenosis and adhesions. Because of the critical condition of horses undergoing colic surgery, it is imperative this is performed as quickly as possible. OBJECTIVES: To evaluate, in vitro, differences in the time of execution and leakage pressure between the Lembert single layer, Gambee and Lembert double layer suture patterns for intestinal anastomosis in the horse and correlate the time taken to complete the anastomosis and hemicircumference of the anastomotic site. METHODS: Small intestinal loops were anastomosed with one of the 3 suture patterns. The intestines, immersed in polyionic solution, were insufflated via a flexible rubber hose, connected to a sphygmomanometer bulb, inserted into the lumen at one end and fixed at 25 cm from the anastomosis site with a locking clip. A tube fixed in the same manner at the other end, connected to a pressure gauge, was used to evaluate the pressure at which leakage from the anastomosis site, revealed by the presence of bubbles, was present. RESULTS: The time spent in the execution of the Lembert single layer was significantly less than that for both Gambee and Lembert double layer. The leakage pressure of Lembert single layer was significantly higher than that recorded for both Gambee and Lembert double layer. CONCLUSIONS AND POTENTIAL RELEVANCE: This study shows that the continuous Lembert single layer pattern takes less time to execute and fails at higher pressures than the Lembert double layer or Gambee patterns. PMID- 22082447 TI - Changes in the content of bioactive polyphenolic compounds of olive mill wastewater by the action of exogenous enzymes. AB - The aim behind the present research is to develop an enzymatic treatment for olive mill wastewater (OMW) to release high amounts of simple phenolics having high antioxidant value. OMW was hydrolyzed by a mixed enzyme preparation rich in beta-glucosidase produced by Aspergillus niger . This research shows that A. niger beta-glucosidase played a major role in the release of simple phenolic compounds from OMW. These compounds were recovered by ethyl acetate extraction and identified by HPLC and LC-MS. The main identified phenolic compound is hydroxytyrosol. The results of enzymatic hydrolysis of OMW under optimum conditions indicated a maximum hydroxytyrosol concentration of 2.9 g L(-1) compared to 0.015 g L(-1) contained in the control (test without added enzyme). The above results prove that OMW is a potential substrate for producing hydroxytyrosol through enzymatic hydrolysis of its glycosides. PMID- 22082448 TI - Perspectives on the role of bioengineering in neurotrauma research. PMID- 22082449 TI - Blast-induced color change in photonic crystals corresponds with brain pathology. AB - A high incidence of blast exposure is a 21st century reality in counter insurgency warfare. However, thresholds for closed-head blast-induced traumatic brain injury (bTBI) remain unknown. Moreover, without objective information about relative blast exposure, warfighters with bTBI may not receive appropriate medical care and may remain in harm's way. Accordingly, we have engineered a blast injury dosimeter (BID) using a photonic crystalline material that changes color following blast exposure. The photonic crystals are fabricated using SU-8 via multi-beam interference laser lithography. The final BID is similar in appearance to an array of small colored stickers that may be affixed to uniforms or helmets in multiple locations. Although durable under normal conditions, the photonic crystalline micro- and nano-structure are precisely altered by blast to create a color change. These BIDs were evaluated using a rat model of bTBI, for which blast shockwave exposure was generated via a compressed air-driven shock tube. With prototype BID arrays affixed to the animals, we found that BID color changes corresponded with subtle brain pathologies, including neuronal degeneration and reactive astrocytosis. These subtle changes were most notable in the dentate gyrus of the hippocampus, cerebral cortex, and cerebellum. These data demonstrate the feasibility of using a materials-based, power-free colorimetric BID as the first self-contained blast sensor calibrated to correspond with brain pathology. PMID- 22082450 TI - Multistep ultrahigh performance liquid chromatography/tandem mass spectrometry analysis for untargeted quantification of glycating activity and identification of most relevant glycation products. AB - The use of advanced glycation end-products (AGEs) as biomarkers for diagnosis and clinical studies is still hampered by insufficient knowledge on clinically relevant structures formed from precursors associated with defined disease states. The present study conducted untargeted analysis of the glycating activity of AGE-precursors by ultrahigh performance liquid chromatography/tandem mass spectrometry multiple reaction monitoring (UHPLC/MSMS-MRM), monitoring the loss of a nonapeptide as the glycation target. Thus, the glycating activities of seven important AGE-precursors were determined (glucose 13% and the reactive carbonyl compounds glucosone 39%, 3-deoxyglucosone 15%, 3-deoxygalactosone 26%, 3,4 dideoxyglucosone-3-ene 79%, methylglyoxal 94%, and glyoxal 97% peptide loss; 12 h/37 degrees C). Furthermore, UHPLC/MSMS with simultaneous precursor ion scan and information-dependent acquisition of enhanced resolution spectra and subsequent product ion scan was applied for untargeted analysis of the major AGE structures derived from various AGE-precursors. The 20 most important modifications could be assigned to 8 AGE-structures previously reported in the literature. Seven loosely bound AGEs not yet covered by conventional methods were detected and assigned to hemiaminals. Five AGE structures did not match any known products. The method can be applied to analyze glycating activity and AGE structures formed from various other precursors under defined reaction conditions, supporting the selection and evaluation of diagnostic AGE-markers for clinical studies. PMID- 22082451 TI - Chemiosmotic coupling summarised. PMID- 22082452 TI - Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. 1966. AB - 50 years ago Peter Mitchell proposed the chemiosmotic hypothesis for which he was awarded the Nobel Prize for Chemistry in 1978. His comprehensive review on chemiosmotic coupling known as the first "Grey Book", has been reprinted here with permission, to offer an electronic record and easy access to this important contribution to the biochemical literature. This remarkable account of Peter Mitchell's ideas originally published in 1966 is a landmark and must-read publication for any scientist in the field of bioenergetics. As far as was possible, the wording and format of the original publication have been retained. Some changes were required for consistency with BBA formats though these do not affect scientific meaning. A scanned version of the original publication is also provided as a downloadable file in Supplementary Information and can be found online at doi:10.1016/j.bbabio.2011.09.018. See also Editorial in this issue by Peter R. Rich. Original title: CHEMIOSMOTIC COUPLING IN OXIDATIVE AND PHOTOSYNTHETIC PHOSPHORYLATION, by Peter Mitchell, Glynn Research Laboratories, Bodmin, Cornwall, England. PMID- 22082453 TI - Transcriptome and membrane fatty acid analyses reveal different strategies for responding to permeating and non-permeating solutes in the bacterium Sphingomonas wittichii. AB - BACKGROUND: Sphingomonas wittichii strain RW1 can completely oxidize dibenzo-p dioxins and dibenzofurans, which are persistent contaminants of soils and sediments. For successful application in soil bioremediation systems, strain RW1 must cope with fluctuations in water availability, or water potential. Thus far, however, little is known about the adaptive strategies used by Sphingomonas bacteria to respond to changes in water potential. To improve our understanding, strain RW1 was perturbed with either the cell-permeating solute sodium chloride or the non-permeating solute polyethylene glycol with a molecular weight of 8000 (PEG8000). These solutes are assumed to simulate the solute and matric components of the total water potential, respectively. The responses to these perturbations were then assessed and compared using a combination of growth assays, transcriptome profiling, and membrane fatty acid analyses. RESULTS: Under conditions producing a similar decrease in water potential but without effect on growth rate, there was only a limited shared response to perturbation with sodium chloride or PEG8000. This shared response included the increased expression of genes involved with trehalose and exopolysaccharide biosynthesis and the reduced expression of genes involved with flagella biosynthesis. Mostly, the responses to perturbation with sodium chloride or PEG8000 were very different. Only sodium chloride triggered the increased expression of two ECF-type RNA polymerase sigma factors and the differential expression of many genes involved with outer membrane and amino acid metabolism. In contrast, only PEG8000 triggered the increased expression of a heat shock-type RNA polymerase sigma factor along with many genes involved with protein turnover and repair. Membrane fatty acid analyses further corroborated these differences. The degree of saturation of membrane fatty acids increased after perturbation with sodium chloride but had the opposite effect and decreased after perturbation with PEG8000. CONCLUSIONS: A combination of growth assays, transcriptome profiling, and membrane fatty acid analyses revealed that permeating and non-permeating solutes trigger different adaptive responses in strain RW1, suggesting these solutes affect cells in fundamentally different ways. Future work is now needed that connects these responses with the responses observed in more realistic scenarios of soil desiccation. PMID- 22082454 TI - Asian perspectives on patient education and health care communication. PMID- 22082455 TI - The influence of light quality on C4 photosynthesis under steady-state conditions in Zea mays and Miscanthus*giganteus: changes in rates of photosynthesis but not the efficiency of the CO2 concentrating mechanism. AB - Differences in light quality penetration within a leaf and absorption by the photosystems alter rates of CO(2) assimilation in C(3) plants. It is also expected that light quality will have a profound impact on C(4) photosynthesis due to disrupted coordination of the C(4) and C(3) cycles. To test this hypothesis, we measured leaf gas exchange, (13) CO(2) discrimination (Delta(13) C), photosynthetic metabolite pools and Rubisco activation state in Zea mays and Miscanthus * giganteus under steady-state red, green, blue and white light. Photosynthetic rates, quantum yield of CO(2) assimilation, and maximum phosphoenolpyruvate carboxylase activity were significantly lower under blue light than white, red and green light in both species. However, similar leakiness under all light treatments suggests the C(4) and C(3) cycles were coordinated to maintain the photosynthetic efficiency. Measurements of photosynthetic metabolite pools also suggest coordination of C(4) and C(3) cycles across light treatments. The energy limitation under blue light affected both C(4) and C(3) cycles, as we observed a reduction in C(4) pumping of CO(2) into bundle-sheath cells and a limitation in the conversion of C(3) metabolite phosphoglycerate to triose phosphate. Overall, light quality affects rates of CO(2) assimilation, but not the efficiency of CO(2) concentrating mechanism. PMID- 22082456 TI - The hierarchical face: higher rankings lead to less cooperative looks. AB - In 3 studies, we tested the hypothesis that the higher ranked an individual's group is, the less cooperative the facial expression of that person is judged to be. Study 1 established this effect among business school deans, with observers rating individuals from higher ranked schools as appearing less cooperative, despite lacking prior knowledge of the latters' actual rankings. Study 2 then experimentally manipulated ranking, showing that the effect of rankings on facial expressions is driven by context rather than by individual differences per se. Finally, Study 3 demonstrated that the repercussions of this effect extend beyond the perception of cooperativeness to tangible behavioral outcomes in social interactions. Theoretical and practical implications of this phenomenon are discussed. PMID- 22082457 TI - Supervisors' upward exchange relationships and subordinate outcomes: testing the multilevel mediation role of empowerment. AB - This study empirically examined the proposition that supervisors' exchange relationships with their own supervisors (i.e., leader-leader exchange, or LLX) are related to their subordinates' work-related outcomes through 3 mechanisms: (a) leaders modeling their LLX to develop and maintain their exchange relationships with their subordinates (i.e., leader-member exchange, or LMX), (b) motivating the team and its members, captured by team and individual empowerment, and (c) facilitating the relationships between LMX and individual outcomes. Analyses of multisource and lagged data from 104 team supervisors and 577 subordinates showed that LMX mediated the positive relationship of LLX on subordinates' individual empowerment. Furthermore, team empowerment and individual empowerment sequentially mediated the positive relationships between LLX and subordinates' job satisfaction and job performance. The authors also found that the indirect relationships of LMX with job satisfaction and job performance via individual empowerment were stronger when LLX was higher. Theoretical and practical implications of these findings are discussed. PMID- 22082458 TI - The impact of help seeking on individual task performance: the moderating effect of help seekers' logics of action. AB - Drawing from achievement-goal theory and the social psychological literature on help seeking, we propose that it is the variance in the logic underpinning employees' help seeking that explains divergent findings regarding the relationship between help seeking and task performance. Using a sample of 110 newly hired customer contact employees, a prospective study design, and archival performance data, we found no evidence of a hypothesized main effect of help seeking on performance. However, we did find that the help seeking-performance relationship was conditioned by the degree to which help seekers endorse 2 alternative help-seeking logics (autonomous vs. dependent logic) such that the level of help seeking is more strongly related to performance among those either more strongly endorsing an autonomous help-seeking logic or more weakly endorsing a dependent help-seeking logic. PMID- 22082459 TI - Treatment-related mortality in children with acute myeloid leukaemia in Central America: incidence, timing and predictors. AB - BACKGROUND: Cure rates in paediatric acute myeloid leukaemia in low-income countries lag behind those in high-income countries, in part secondary to higher rates of treatment-related mortality. Patterns of treatment-related mortality are likely to differ between low and high-income centres. Understanding low-income setting patterns is necessary before effective interventions aimed at decreasing treatment-related mortality can be designed. Our aim was to describe the incidence, timing and predictors of treatment-related mortality among Central American children with acute myeloid leukaemia. PATIENTS AND METHODS: We evaluated patients younger than 21 years diagnosed with acute myeloid leukaemia from 2000 to 2008 in El Salvador, Honduras or Guatemala. Biologic, socioeconomic and nutritional variables collected prospectively were examined as potential predictors of treatment-related mortality. RESULTS: Among 279 patients, treatment related mortality occurred in 65 (23%). Of 65 deaths, 51 (78.5%) occurred before or during induction, resulting in an early death rate of 18.3%. The most common causes of treatment-related mortality were infection (29/65; 45%) and haemorrhage (13/65; 20%). Infection accounted for 33% of treatment-related mortality before remission induction therapy versus 40% during induction and 77% after induction (P = 0.03). Rates of treatment-related mortality did not vary between time periods 1 and 2 (24.8% versus 21.4%; P = 0.32). Only lower initial platelet count predicted early death (odds ratio per 10 * 10(9)/L = 0.88, 95% Confidence Interval (CI) 0.79-0.97; P < 0.001). CONCLUSIONS: Treatment-related mortality remains a significant cause of treatment failure. Supportive care interventions are needed. Children presenting with low initial platelet counts were at highest risk of induction death, suggesting that transfusion practices should be evaluated. PMID- 22082461 TI - Changing age of acne vulgaris visits: another sign of earlier puberty? AB - The objective of the current study was to assess changes in the onset of pubertal maturation by determining whether acne is occurring at an earlier age. We assessed the age at which acne is occurring by assessing trends in the age of people seeking medical attention for acne. The National Ambulatory Medical Care Survey database was used to analyze physician visits for acne vulgaris in children aged 6 to 18 from 1979 to 2007. The data were used to assess trends in the mean age of children with acne and to compare these trends according to race and sex. Regression analysis revealed a significant decrease in the mean age of children seeking treatment for acne over this 28-year period (p < 0.001). There was no significant change in the mean age of black children seeking treatment for acne. Black girls had the lowest mean age whereas white boys had the highest mean age. There has been a decrease in the average age of children seeking treatment for acne that may be indicative of earlier acne onset. This finding provides supporting evidence of the increasingly earlier onset of puberty in girls. PMID- 22082462 TI - A retrospective study of the management of pediatric kerion in Trichophyton tonsurans infection. AB - Kerion celsi is the inflammatory extreme of tinea capitis, representing a delayed hypersensitivity reaction to the causative dermatophyte. Some authors have advocated the use of oral corticosteroids in patients with kerion formation to inhibit the host inflammatory response and minimize the risk of scarring. This retrospective study analyzed the management and outcome of all children younger than 10 years old presenting to our pediatric dermatology service with tinea capitis resulting in kerion formation between 2003 and 2009. We propose that kerion treatment be directed toward the underlying dermatophyte. Oral and intralesional corticosteroids are an unnecessary adjunct to oral antifungal therapy for children with tinea capitis presenting with kerion in urban areas. PMID- 22082460 TI - Functional connectivity during language processing in acute cocaine withdrawal: a pilot study. AB - Recent research revealed decreased access to semantic and associative networks in acute cocaine withdrawal. In autism, such behavioral outcomes are associated with decreased functional connectivity using functional magnetic resonance imaging. Therefore, we wished to determine whether connectivity is also decreased in acute cocaine withdrawal. Eight subjects in acute cocaine withdrawal were compared to controls for connectivity in language areas while performing a task involving categorization of words according to semantic and phonological relatedness. Acute withdrawal subjects had significantly less overall connectivity during semantic relatedness, and a trend towards less connectivity during phonological relatedness. Of potential future interest is whether this might serve as an imaging marker for treatment in patients. PMID- 22082463 TI - Recurrence of infantile hemangiomas treated with propranolol. AB - Propranolol has shown to be effective in the treatment of infantile hemangiomas (IH), but several cases of recurrences have been reported so far. We describe five cases of IH recurrence after propranolol treatment was stopped in 26 patients treated with propranolol all of whom were observed for at least 9 months after treatment was discontinued. Recurrence was present in 5 of 26 cases, yielding a recurrence rate of 19%. All cases were in females. Time from withdrawal to recurrence ranged from 0 to 6 months. In four of five cases, the lesion relapsed after the age of 11 months. Four of the five cases presented partial recurrences, whereas in one case, recurrence was complete. In the majority of cases, recurrence appeared in the deep component of the IH. Early treatment withdrawal or a long proliferative phase of IH are potential causes of hemangioma recurrence, although the exact mechanism remains unclear. The vascular endothelial growth factor receptor might be involved, as well as incomplete apoptosis during treatment. PMID- 22082464 TI - Acute generalized exanthematous pustulosis and Coombs-positive hemolytic anemia in a child following Loxosceles reclusa envenomation. AB - Previously reported cases of acute generalized exanthematous pustulosis secondary to brown recluse spider bite have been questioned due to lack of identification of the spider or because of the concomitant administration of antibiotics. We report a 9-year-old boy who arrived at the emergency department with a confirmed Loxosceles reclusa bite to the neck. On the third day of hospitalization, he developed hundreds of monomorphous, sterile pustules, initially in intertriginous areas. The eruption disseminated and was followed by pinpoint desquamation typical for acute generalized exanthematous pustulosis. During this he also developed late onset Coombs-positive hemolytic anemia and systemic loxoscelism. Sphingomyelinase in Loxosceles venom induces the production of interleukin-8 and granulocyte-macrophage colony-stimulating factor, cytokines involved in the pathogenesis of acute generalized exanthematous pustulosis, providing a mechanism by which Loxosceles reclusa bite may trigger acute generalized exanthematous pustulosis. We suggest that this case adds Loxosceles envenomation to the spectrum of agents that can trigger acute generalized exanthematous pustulosis. PMID- 22082465 TI - Novel SLC39A4 mutation in acrodermatitis enteropathica. AB - Acrodermatitis enteropathica (AE) is a rare autosomal-recessive disorder characterized by dermatitis, alopecia, diarrhea, and retardation of growth and development. AE maps to 8q24.3 and is associated with mutations in the intestinal zinc transporter ZIP4 encoded by the gene SLC39A4. We describe a novel homozygous mutation, 1191insC, in SLC39A4 in a patient from Sierra Leone and suggest that AE should be considered within the differential diagnosis for acrodermatitis in children from Sierra Leone. Genetic testing for this founder mutation can be easily performed for this treatable disorder. PMID- 22082466 TI - A challenging case: Symmetrical drug related intertriginous and flexural exanthem, fixed drug eruption, or both? AB - We herein report a 12-year-old boy with amoxicillin-induced, recurrent, site specific, symmetrical, sharply demarcated reddish plaques on the buttocks and the major flexural and intertriginous areas. The lesions resolved with topical corticosteroids, leaving hyperpigmentation. Histopathology showed nonspecific features of inflammation and dermal melanophages. Amoxicillin was the probable inducer based on oral provocation test with Amoksina((r)) tablet, however patch testing with amoxicillin on previously affected and unaffected skin remained negative. The diagnosis was challenging because of the overlapping features of symmetrical drug-related intertriginous and flexural exanthema and fixed drug eruption. This one represents a unique and challenging one with overlapping clinical features of symmetrical drug-related intertriginous and flexural exanthem (SDRIFE) and fixed drug eruption (FDE). We discuss the possible immunopathogenetic mechanisms leading to the simultaneous occurrence of different phenotypes of drug eruption in the same patient. PMID- 22082467 TI - Phacomatosis pigmentokeratotica: a further case without extracutaneous anomalies and review of the condition. AB - Epidermal nevus syndrome is the term for the association of an epidermal nevus and extracutaneous anomalies, including neurologic, ophthalmic, and skeletal defects. Epidermal nevus syndromes include different disorders that share the feature of mosaicism. Phacomatosis pigmentokeratotica (PPK) is a distinctive new epidermal nevus syndrome first described in 1996 characterized by the presence of multiple organoid nevi with sebaceous differentiation, a speckled lentiginous nevus, and skeletal and neurologic abnormalities. Only a handful of cases of PPK without extracutaneous manifestations have been reported. We report here an individual with PPK with only cutaneous signs and confirm this distinctive syndrome has two subtypes according to the presence or absence of extracutaneous involvement. PMID- 22082468 TI - Asymptomatic purpuric lesions in segmental arrangement in a 10-year-old boy. PMID- 22082469 TI - Generalized eruptive white papules in a 9-year-old boy. PMID- 22082470 TI - Petechial-like lesions, eye abnormalities, and albuminuria in a young boy. PMID- 22082471 TI - Atypical diaper dermatitis: contact allergy to mercapto compounds. AB - We present a case of allergic contact dermatitis in an 18-month-old boy caused by type-IV allergy to mercapto mix and mercaptobenzothiazole as components of the elastic border of diapers. Allergic contact dermatitis should be included in the differential diagnosis of diaper dermatitis, especially in difficult-to-treat cases or atypical clinical presentation. PMID- 22082472 TI - Speckled lentiginous nevus syndrome: central nervous system abnormalities as a critical diagnostic feature. PMID- 22082473 TI - Marie-Unna hereditary hypotrichosis or autosomal recessive hereditary hypotrichosis with woolly hair: the diagnostic dilemma of labeling cases with hypotrichosis. PMID- 22082475 TI - Diffusion tensor imaging in episodic cluster headache. AB - BACKGROUND: Cluster headache (CH) is a rare headache disorder with severe unilateral headache bouts and autonomic symptoms. The pathophysiology of CH is not completely understood. Using a voxel-based morphometric paradigm or functional imaging, a key role of the hypothalamus and the pain matrix could be demonstrated during CH episodes. However, there are no diffusion tensor imaging (DTI) data investigating the white matter microstructure of the brain in patients with CH. Therefore, we used DTI to delineate microstructural changes in patients with CH in a headache-free state. METHODS: Seven male patients with episodic CH and 7 healthy subjects were included and examined with a routine 1.5 T magnetic resonance imaging scanner. Whole-head DTI scans measuring fractional anisotropy were analyzed without a priori hypotheses using track-based spatial statistics. RESULTS: We found significant microstructural brain tissue changes bilaterally in the white matter of the brainstem, the frontal lobe, the temporal lobe, the occipital lobe, the internal capsule, and on the right side of thalamus and cerebellum. There were further lesions in the basal frontal lobe that were part of the olfactory system. Alterations of fractional anisotropy in the brainstem might indicate changes of the medial lemniscus and central sympathetic pathways. CONCLUSIONS: Patients with episodic CH have microstructural brain changes in regions that belong to the pain matrix. Furthermore, we were able to detect structural changes suggesting an involvement of the olfactory system as well as lesions in the brainstem indicating an involvement of trigeminal and sympathetic systems. PMID- 22082476 TI - Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats. AB - BACKGROUND: Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an in vivo rat model of acute ischemic stroke. METHODS: Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1beta, TNF-alpha, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra. RESULTS: 24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p=0.001), cortical (p=0.002), and basal ganglia (p=0.036) infarct volumes. Hippocampal infarct volumes (p=0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1beta (79%; p<0.001), TNF-alpha (59%; p=0.001), IL-6 (47%; p=0.04), and CD11B (49%; p=0.001) in the infarcted cortex compared to controls. CONCLUSIONS: Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions. PMID- 22082477 TI - The TWEAK-Fn14 system: breaking the silence of cytokine-induced skeletal muscle wasting. AB - The occurrence of skeletal muscle atrophy, a devastating complication of a large number of disease states and inactivity/disuse conditions, provides a never ending quest to identify novel targets for its therapy. Proinflammatory cytokines are considered the mediators of muscle wasting in chronic diseases; however, their role in disuse atrophy has just begun to be elucidated. An inflammatory cytokine, tumor necrosis factor (TNF)- like weak inducer of apoptosis (TWEAK), has recently been identified as a potent inducer of skeletal muscle wasting. TWEAK activates various proteolytic pathways and stimulates the degradation of myofibril protein both in vitro and in vivo. Moreover, TWEAK mediates the loss of skeletal muscle mass and function in response to denervation, a model of disuse atrophy. Adult skeletal muscle express very low to minimal levels of TWEAK receptor, Fn14. Specific catabolic conditions such as denervation, immobilization, or unloading rapidly increase the expression of Fn14 in skeletal muscle which in turn stimulates the TWEAK activation of various catabolic pathways leading to muscle atrophy. In this article, we have discussed the emerging roles and the mechanisms of action of TWEAK-Fn14 system in skeletal muscle with particular reference to different models of muscle atrophy and injury and its potential to be used as a therapeutic target for prevention of muscle loss. PMID- 22082478 TI - Trends in wound repair: cellular and molecular basis of regenerative therapy using electromagnetic fields. AB - Chronic ulceration of the leg represents a major, underestimated problem of modern health care, involving physical and cosmetic impairment and social stigma along with high community costs for patients' treatment. The increasing prevalence of chronic ulcers, currently reported to be as much as 0.3% in the general population, should stimulate identification of more efficacious therapeutic approaches to achieve complete healing. The strategies of regenerative medicine based on small molecules, biomimetic scaffolds, gene or cell therapy, and electromagnetic field manipulation represent some of the modern therapeutic alternatives for wound healing. Here we review in an integrated, interdisciplinary approach the modern cellular and molecular mechanistic concepts regarding the involvement of extremely low frequency electromagnetic fields (ELF EMF) in the complex process of tissue repair, with particular focus on chronic wounds. The data analysis supports three main effects of electromagnetic fields on the wound healing pathways: 1) an antiinflammatory effect, by modulation of cytokine profile that induces the transition of the healing process from a chronic pro-inflammatory to an anti-inflammatory state; 2) a neo-angiogenic effect, by increased endothelial cells proliferation and tubulization and production of fibroblast growth factor (FGF)-2; and 3) a reepithelialization effect, by stimulation of collagen formation. We believe that utilization of ELF EMF in larger clinical trials designed to optimize these functional parameters would facilitate a better understanding of ELFEMF- induced healing mechanisms and lead to improved therapeutic outcomes for this disabling condition which is often totally resistant to treatment. PMID- 22082479 TI - miR221/222 in cancer: their role in tumor progression and response to therapy. AB - miRNAs are small non-coding RNAs of ~24 nt that can block mRNA translation and/or negatively regulate its stability. There is a large body of evidence that dysregulation of miRNAs is a hallmark of cancer. miRNAs are often aberrantly expressed and their function is linked to the regulation of oncogenes and/or tumor suppressor genes involved in cell signaling pathway. miR-221 and miR-222 are two highly homologous microRNAs, whose upregulation has been recently described in several types of human tumors. miR-221/222 have been considered to act as oncogenes or tumor suppressors, depending on tumor system. Silencing oncomiRs or gene therapy approaches, based on re-expression of miRNAs that are down-regulated in cancer cells, could represent a novel anti-tumor approach for integrated cancer therapy. Here we will review the role of miR-221/222 in cancer progression and their use as prognostic and therapeutic tools in cancer. PMID- 22082481 TI - Nitric oxide and cancer: the emerging role of S-nitrosylation. AB - Nitric oxide (NO) is a short-lived, endogenously produced gas that is highly diffusible across cell membranes and acts as a signaling molecule in the body. The redox state and chemistry of NO facilitate its interaction with various proteins thus regulating various intracellular and intercellular events. One of the key mechanisms by which NO regulates the function of various target proteins is through the coupling of a nitroso moiety from NO-derived metabolites to a reactive cysteine leading to the formation of a S-nitrosothiol (SNO), a process commonly known as S-nitrosylation. S-nitrosylation signaling events within the cell have led to the discovery of many other physiological functions of NO in many other types of cells including cancer cells. Only recently are the diverse roles of S-nitrosylation in cancer beginning to be understood. In the present review we discuss the recent evidence for the diverse roles of NO/SNO-related mechanisms in cancer biology and therapy, including the participation of NO in the pathogenesis of cancer, its duality in protecting against or inducing cancer cell death and the contribution of NO to metastatic processes. In addition, NO can be therapeutically used in the reversal of tumor cell resistance to cytotoxic drugs and as a sensitizing agent to chemo- and radiotherapy. Finally, recent studies providing evidence for NO-related mechanisms of epigenetic gene expression regulation will also be discussed. Undoubtedly, new exciting results will contribute to this rapidly expanding area of cancer research. PMID- 22082482 TI - The emerging role of endocrine disruptors in pathogenesis of insulin resistance: a concept implicating nonalcoholic fatty liver disease. AB - Endocrine disruptors or endocrine-disrupting chemicals (EDCs) represent a highly heterogeneous group of molecules found in the environment or in consumer products. Toxicology and epidemiology studies have suggested the involvement of diverse EDCs in an increasing number of metabolic disorders, including insulin resistance (IR) and IR-related co morbidities, such as obesity, type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome. Nonalcoholic fatty liver disease (NAFLD), another IR related condition, is emerging as a significant public health concern, affecting 30-45% of the general population in the Western world. To evaluate whether EDCs may also play a role in the pathogenesis of NAFLD, we reviewed the literature on well-studied EDCs, such as dioxins, bisphenol A, phthalates and other persistent organic pollutants, in relation to pathways that might contribute to the pathogenesis of fatty liver / NAFDL. Certain EDCs may be responsible for inducing alterations similar to those encountered in NAFLD either directly through a hepatotoxic effect and/or indirectly by triggering hepatic and systematic IR. Considering these effects, which act in concert with the effects of the epidemics of obesity and T2DM, EDCs may play a significant role in the pathogenesis of fatty liver, thereby increasing the prevalence of NAFLD worldwide. Translational studies and clinical trials investigating the association between EDCs and NAFLD are required to confirm and extent these studies. PMID- 22082480 TI - Hematopoietic stem cells: transcriptional regulation, ex vivo expansion and clinical application. AB - Maintenance of ex vivo hematopoietic stem cells (HSC) pool and its differentiated progeny is regulated by complex network of transcriptional factors, cell cycle proteins, extracellular matrix, and their microenvironment through an orchestrated fashion. Strides have been made to understand the mechanisms regulating in vivo quiescence and proliferation of HSCs to develop strategies for ex vivo expansion. Ex vivo expansion of HSCs is important to procure sufficient number of stem cells and as easily available source for HSC transplants for patients suffering from hematological disorders and malignancies. Our lab has established a nanofiber-based ex vivo expansion strategy for HSCs, while preserving their stem cell characteristics. Ex vivo expanded cells were also found biologically functional in various disease models. However, the therapeutic potential of expanded stem cells at clinical level still needs to be verified. This review outlines transcriptional factors that regulate development of HSCs and their commitment, genes that regulate cell cycle status, studies that attempt to develop an effective and efficient protocol for ex vivo expansion of HSCs and application of HSC in various non-malignant and malignant disorders. Overall the goal of the current review is to deliver an understanding of factors that are critical in resolving the challenges that limit the expansion of HSCs in vivo and ex vivo. PMID- 22082483 TI - HCV infection by cell-to-cell transmission: choice or necessity? AB - In vitro models of HCV infection have allowed for the clarifying of molecules and mechanisms involved in the main steps of virus cell-entry. HCV entry and neutralization appear to be closely related. Neutralizing antibodies inhibit the E2-CD81 binding, therefore CD81 is considered to be a major target of immune response. The tight-junction proteins are also implicated in E2-binding to CD81 and successive steps of virus entry, in cooperation with several co-receptors, whose involvement has still to be elucidated. Increasing evidence has emphasized the importance of cell-to-cell HCV-transmission in chronic infection. This route for infection could favour virus-escape from host-neutralization though its CD81 dependency is still debated. The main reasons which have delayed our understanding of HCV-infection are here critically reviewed, as are the challenges faced by investigators in the field. A deeper insight into the different pathways involved could help to elucidate some crucial features of HCV infection mechanisms and disclose important implications in its pathogenesis, which could help in suggesting new targets for successful immune prophylactic/therapeutic strategies. PMID- 22082484 TI - Involvement of IL-1R/TLR signalling in experimental autoimmune encephalomyelitis and multiple sclerosis. AB - Multiple sclerosis is a complex disease characterised by chronic inflammation, demyelination and axonal pathology resulting in progressive neurological disabilities. Multiple sclerosis is generally considered to be an autoimmune disease, even though the primary cause of the underlying autoimmune response is unknown. Epidemiological evidence suggests that both genetic and environmental factors play a key role in susceptibility to multiple sclerosis; however, the relative contributions of these factors in triggering the onset of the disease remain unclear. Several studies indicate that receptors belonging to the Interleukin-1 and Toll-like receptor families are crucially involved in the mechanisms underlying the development of experimental autoimmune encephalomyelitis, an animal model that mimics multiple sclerosis. Moreover, recent evidence highlights the importance of downstream signalling proteins in the Interleukin-1 and Toll-like receptor signalling pathways, namely, myeloid differentiation primary response protein 88 and Interleukin-1-receptor-associated kinase. This review summarises the current knowledge concerning the involvement of Interleukin-1/Toll-like receptor signalling in the development of experimental autoimmune encephalomyelitis and multiple sclerosis. A deeper understanding of the role of these important pathways in the pathogenesis of experimental autoimmune encephalomyelitis may eventually yield clinical benefits in the treatment of central nervous system-based inflammatory disorders. PMID- 22082485 TI - DNA repair mechanisms in colorectal carcinogenesis. AB - Colon cancer is among the most common cancers and the third cause of cancer deaths worldwide. If detected at an early stage, treatment might often lead to cure. The present review adduces the so far studied alterations in the expression of genes, as well as polymorphisms of genes engaged in DNA repair systems, with particular emphasis on indirect ones that are correlated with colorectal cancer. Such aberrations could be linked to an increased risk for the development of colorectal cancer and might serve as potential targets in the areas of prevention and therapy. PMID- 22082487 TI - Tomato plants overexpressing cryptochrome 2 reveal altered expression of energy and stress-related gene products in response to diurnal cues. AB - In order to sense and respond to the fluctuating light conditions, higher plants possess several families of photoreceptors, such as phytochromes (PHYs), cryptochromes (CRYs) and phototropins. CRYs are responsible for photomorphogenesis and play a role in circadian, developmental and adaptive growth regulation of plants. In tomato (Solanum lycopersicum), CRY2 controls vegetative development, flowering time, fruit antioxidant content as well as the diurnal transcription of several other photoreceptor genes. We applied large scale molecular approaches to identify altered transcripts and proteins in tomato wild-type (WT) versus a CRY2 overexpressing transgenic genotype, under a diurnal rhythm. Our results showed that tomato CRY2 profoundly affects both gene and protein expression in response to daily light cycle. Particularly altered molecular pathways are related to biotic/abiotic stress, photosynthesis, including components of the light and dark reactions and of starch and sucrose biosynthesis, as well as to secondary metabolism, such as phenylpropanoid, phenolic and flavonoid/anthocyanin biosynthesis pathways. One of the most interesting results is the coordinated up-regulation, in the transgenic genotype, of a consistent number of transcripts and proteins involved in photorespiration and photosynthesis. It is conceivable that light modulates the energetic metabolism of tomato through a fine CRY2-mediated transcriptional control. PMID- 22082488 TI - Dissociation, trauma, and the role of lived experience: toward a new conceptualization of voice hearing. AB - Voice hearing (VH) is often regarded as pathognomic for schizophrenia. The purpose of this article is to review and integrate historical, clinical, epidemiological, and phenomenological evidence in order to suggest that VH may be more appropriately understood as a dissociative rather than a psychotic phenomenon. First, we discuss the lifetime prevalence of VH in the general population, which is estimated to range between 1% and 16% for adult nonclinical populations and 2% and 41% in healthy adolescent samples. Second, we demonstrate how the ubiquity of VH phenomenology, including variables like voice location, content, and frequency, limits its diagnostic and prognostic utility for differentiating psychotic from trauma-spectrum and nonclinical populations. Finally, we report on the empirical associations between VH, measures of dissociation, and trauma particularly (though not exclusively) childhood sexual abuse. There are 2 main conclusions from this review. First, we argue that available evidence suggests that VH experiences, including those in the context of psychotic disorders, can be most appropriately understood as dissociated or disowned components of the self (or self-other relationships) that result from trauma, loss, or other interpersonal stressors. Second, we provide a rationale for clinicians to use psychotherapeutic methods for integrating life events as precipitating and/or maintaining factors for distressing voices. Potential mechanisms for the relationship between trauma, dissociation, VH, and clinical diagnosis are described, including the relevance of literature from the field of attachment in providing a diathesis for dissociation. Suggestions for future research are also discussed. PMID- 22082489 TI - Elevation of serum high molecular weight adiponectin in patients with Type 2 diabetes and orthostatic hypotension: association with arterial stiffness and hypercoagulability. AB - AIM: Orthostatic hypotension is a hallmark of diabetic autonomic neuropathy and is associated with increased mortality. The serum level of adiponectin is elevated in patients with heart failure or renal failure. In the present study, we measured serum levels of total and high molecular weight adiponectin in patients with Type 2 diabetes and orthostatic hypotension. We also investigated the relationship between the presence of orthostatic hypotension and various clinical variables in patients with Type 2 diabetes. METHODS: We studied 105 patients with Type 2 diabetes. Orthostatic hypotension was defined as a decrease of 20 mmHg or more in systolic blood pressure and/or 10 mmHg in diastolic blood pressure when blood pressure was measured for 3 min while standing. The brachial ankle pulse-wave velocity was also measured as an index of arterial stiffness. RESULTS: Orthostatic hypotension was found in 30 patients with diabetes (28.6%). The haematocrit and estimated glomerular filtration rate were significantly lower in patients with orthostatic hypotension than in those without it. Brachial-ankle pulse-wave velocity and serum total and high molecular weight adiponectin were significantly higher in patients with orthostatic hypotension than in those without. Furthermore, the high molecular weight/total adiponectin ratio was higher in patients with orthostatic hypotension than in those without and hypertension was more common in patients with orthostatic hypotension. Plasma prothrombin F1 + 2, a coagulation maker, was higher in patients with orthostatic hypotension than in those without, while there were no differences of fibrinolytic markers between the two groups. Multivariate analysis showed that HDL cholesterol, haematocrit, F1 + 2, brachial-ankle pulse-wave velocity and a decline of systolic blood pressure on standing were independent determinants of high molecular weight adiponectin. CONCLUSIONS: Patients with Type 2 diabetes and orthostatic hypotension had an elevated serum level of high molecular weight adiponectin, which was associated with the simultaneous presence of renal dysfunction, anaemia, arterial stiffness and hypercoagulability. PMID- 22082486 TI - Basal breast cancer: a complex and deadly molecular subtype. AB - During the last decade, gene expression profiling of breast cancer has revealed the existence of five molecular subtypes and allowed the establishment of a new classification. The basal subtype, which represents 15-25% of cases, is characterized by an expression profile similar to that of myoepithelial normal mammary cells. Basal tumors are frequently assimilated to triple-negative (TN) breast cancers. They display epidemiological and clinico-pathological features distinct from other subtypes. Their pattern of relapse is characterized by frequent and early relapses and visceral locations. Despite a relative sensitivity to chemotherapy, the prognosis is poor. Recent characterization of their molecular features, such as the dysfunction of the BRCA1 pathway or the frequent expression of EGFR, provides opportunities for optimizing the systemic treatment. Several clinical trials dedicated to basal or TN tumors are testing cytotoxic agents and/or molecularly targeted therapies. This review summarizes the current state of knowledge of this aggressive and hard-to-treat subtype of breast cancer. PMID- 22082490 TI - Simvastatin protects auditory hair cells from gentamicin-induced toxicity and activates Akt signaling in vitro. AB - BACKGROUND: Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, known as statins, are commonly used as cholesterol-lowering drugs. During the past decade, evidence has emerged that statins also have neuroprotective effects. Research in the retina has shown that simvastatin, a commonly used statin, increases Akt phosphorylation in vivo, indicating that the PI3K/Akt pathway contributes to the protective effects achieved. While research about neuroprotective effects have been conducted in several systems, the effects of statins on the inner ear are largely unknown. RESULTS: We evaluated whether the 3 hydroxy-3-methylglutaryl-coenzyme A reductase is present within the rat cochlea and whether simvastatin is able to protect auditory hair cells from gentamicin induced apoptotic cell death in a in vitro mouse model. Furthermore, we evaluated whether simvastatin increases Akt phosphorylation in the organ of Corti. We detected 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in organ of Corti, spiral ganglion, and stria vascularis by reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, we observed a dose-dependent and significant reduction of hair cell loss in organs of Corti treated with simvastatin in addition to gentamicin, as compared to samples treated with gentamicin alone. The protective effect of simvastatin was reversed by addition of mevalonate, a downstream metabolite blocked by simvastatin, demonstrating the specificity of protection. Finally, Western blotting showed an increase in organ of Corti Akt phosphorylation after simvastatin treatment in vitro. CONCLUSION: These results suggest a neuroprotective effect of statins in the inner ear, mediated by reduced 3-hydroxy-3-methylglutaryl-coenzyme A reductase metabolism and Akt activation. PMID- 22082492 TI - Host quality and spatial patterning in infections of the Eastern mudsnail (Ilyanassa obsoleta) by two trematodes (Himasthla quissetensis and Zoogonus rubellus). AB - Several studies have suggested that the fitness of a parasite can be directly impacted by the quality of its host. In such cases, selective pressures could act to funnel parasites towards the highest-quality hosts in a population. The results of this study demonstrate that snail host quality is strongly correlated with spatial patterning in trematode infections and that habitat type is the underlying driver for both of these variables. Two trematodes (Himasthla quissetensis and Zoogonus rubellus) with very different life cycles assume the same spatial infection pattern in populations of the first intermediate host (Ilyanassa obsoleta) in coastal marsh habitats. Infected snails are disproportionately recovered from intertidal panne habitats, which offer more hospitable environs for snails than do adjacent habitats (intertidal creeks, coastal flats, and subtidal creeks), in terms of protection from turbulence and wave action, as well as the availability of food stuffs. Snails in intertidal panne habitats are of higher quality when assessed in terms of average size specific mass, growth rate, and fecundity. In mark-recapture experiments, snails frequently dispersed into intertidal pannes but were never observed leaving them. In addition, field experiments demonstrate that snails confined to intertidal panne habitats are disproportionately infected by both trematode species, relative to conspecifics confined to adjacent habitats. Laboratory experiments show that infected snails suffer significant energetic losses and consume more than uninfected conspecifics, suggesting that infected snails in intertidal pannes may survive better than in adjacent habitats. We speculate that 1 possible mechanism for the observed patterns is that the life cycles of both trematode species allows them to contact the highest-quality snails in this marsh ecosystem. PMID- 22082491 TI - Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation. AB - RATIONALE: Fetal cells enter the maternal circulation during pregnancy and may persist in maternal tissue for decades as microchimeras. OBJECTIVE: Based on clinical observations of peripartum cardiomyopathy patients and the high rate of recovery they experience from heart failure, our objective was to determine whether fetal cells can migrate to the maternal heart and differentiate to cardiac cells. METHODS AND RESULTS: We report that fetal cells selectively home to injured maternal hearts and undergo differentiation into diverse cardiac lineages. Using enhanced green fluorescent protein (eGFP)-tagged fetuses, we demonstrate engraftment of multipotent fetal cells in injury zones of maternal hearts. In vivo, eGFP+ fetal cells form endothelial cells, smooth muscle cells, and cardiomyocytes. In vitro, fetal cells isolated from maternal hearts recapitulate these differentiation pathways, additionally forming vascular tubes and beating cardiomyocytes in a fusion-independent manner; ~40% of fetal cells in the maternal heart express Caudal-related homeobox2 (Cdx2), previously associated with trophoblast stem cells, thought to solely form placenta. CONCLUSIONS: Fetal maternal stem cell transfer appears to be a critical mechanism in the maternal response to cardiac injury. Furthermore, we have identified Cdx2 cells as a novel cell type for potential use in cardiovascular regenerative therapy. PMID- 22082493 TI - Themes elicited during motivational interviewing to improve glycaemic control in adults with Type 1 diabetes mellitus. AB - AIMS: To elicit the barriers and motivators to better diabetes self care in patients with Type 1 diabetes. METHODS: We obtained a purposive sample of 47 patients with Type 1 diabetes and persistent suboptimal glycaemic control from a randomized controlled trial of nurse-delivered psychological interventions. Each participant's second session of motivational interviewing was analysed using content analysis. RESULTS: Four major themes emerged: emotions of living with Type 1 diabetes, perceived barriers to diabetes management, motivators for change and methods of coping. Increased assistance and support from family and healthcare teams, the prospect of improved emotional and physical well-being and feelings of success were described as factors that might motivate participants to practice more effective self care. CONCLUSIONS: An enhanced awareness of the range of psychological concepts in diabetes may enable a better therapeutic relationship between clinicians and patients. PMID- 22082495 TI - A wearable robotic knee orthosis for gait training: a case-series of hemiparetic stroke survivors. AB - BACKGROUND AND AIM: Until recently, robotic devices for stroke rehabilitation had multi-joint designs that were often tethered to a treadmill for gait training. A new single-joint wearable robotic knee orthosis (RKO) has been designed that provides patient-initiated powered-assistance in untethered functional mobility. This case-series documents application of the wearable RKO in untethered functional training with stroke survivors. TECHNIQUE: Three ambulatory adult stroke survivors used a wearable RKO during 18 one-hour sessions within a six week physical therapy programme. Subjects were assessed with a variety of balance, gait and functional tests including the Berg Balance Scale (BBS); six minute walk test (6MWT); and Emory Functional Ambulation Profile (EFAP) at pre treatment, post-treatment, one-month and three-month follow-up. DISCUSSION: All subjects improved balance, gait and functional performances with mean individual improvements of 12.6% for BBS, 12.0% for 6MWT and 16.7% for EFAP post-treatment. No adverse events occurred. These three stroke survivors may have benefited from the task-specific functional training programme augmented by RKO use. PMID- 22082494 TI - Inhibin removes the inhibitory effects of activin on steroid enzyme expression and androgen production by normal ovarian thecal cells. AB - Activin and inhibin are important local modulators of theca cell steroidogenesis in the ovary. Using a serum-free primary theca cell culture system, this study investigated the effects of inhibin on theca cell androgen production and expression of steroidogenic enzymes. Androstenedione secretion from theca cells cultured in media containing activin, inhibin and follistatin was assessed by RIA over 144 h. Activin (1-100 ng/ml) suppressed androstenedione production. Inhibin (1-100 ng/ml) blocked the suppressive effects of added activin, but increased androstenedione production when added alone, suggesting it was blocking endogenous activin produced by theca cells. Addition of SB-431542 (activin receptor inhibitor) and follistatin (500 ng/ml) increased androstenedione production, supporting this concept. Infection of theca cells with adenoviruses expressing inhibitory Smad6 or 7 increased androstenedione secretion, confirming that the suppressive effects of activin required activation of the Smad2/3 pathway. Activin decreased the expression levels of steroidogenic acute regulatory protein (STAR), whereas STAR expression was increased by inhibin and SB-431542, alone and in combination. CYP11A was unaffected. The expression of CYP17 encoding 17alpha-hydroxylase was unaffected by activin but increased by inhibin and SB-431542, and when added in combination the effect was further enhanced. The expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) was significantly decreased by activin, while inhibin alone and in combination with SB-431542 both potently increased the expression of 3beta-HSD. In conclusion, activin suppressed theca cell androstenedione production by decreasing the expression of STAR and 3beta-HSD. Inhibin and other blockers of activin action reversed this effect, supporting the concept that endogenous thecal activin modulates androgen production in theca cells. PMID- 22082496 TI - Non-universal equilibrium crystal shape results from sticky steps. AB - The anisotropic surface free energy, Andreev surface free energy and equilibrium crystal shape (ECS) z = z(x,y) are calculated numerically using a transfer matrix approach with the density matrix renormalization group (DMRG) method. The adopted surface model is a restricted solid-on-solid (RSOS) model with 'sticky' steps, i.e. steps with a point-contact-type attraction between them (p-RSOS model). By analyzing the results, we obtain a first-order shape transition on the ECS profile around the (111) facet; and on the curved surface near the (001) facet edge, we obtain shape exponents having values different from those of the universal Gruber-Mullins-Pokrovsky-Talapov (GMPT) class. In order to elucidate the origin of the non-universal shape exponents, we calculate the slope dependence of the mean step height of 'step droplets' (bound states of steps) (n(p)) using the Monte Carlo method, where p = (?z/?x,?z/?y) and (.) represents the thermal average. Using the result of the |p| dependence of (n(p)), we derive a |p|-expanded expression for the non-universal surface free energy f(eff)(p), which contains quadratic terms with respect to |p|. The first-order shape transition and the non-universal shape exponents obtained by the DMRG calculations are reproduced thermodynamically from the non-universal surface free energy f(eff)(p). PMID- 22082497 TI - The 2011-2012 flu season is upon us. PMID- 22082498 TI - Survival of bacterial pathogens on paper and bacterial retrieval from paper to hands: preliminary results. AB - BACKGROUND: Paper is omnipresent on hospital units, but few studies have examined the possible role of paper in the spread of nosocomial pathogens. OBJECTIVE: To determine by laboratory investigation how long bacterial pathogens can survive on office paper and whether bacteria can be transferred from hands to paper and back to hands in a "worst-case scenario." METHODS: Samples of four bacterial pathogens (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus hirae) were prepared according to standard laboratory procedures. Sterile swatches of office paper were inoculated with the pathogens and bacterial survival was tested over seven days. To test the transmission of bacteria from one person's hands to paper and back to another person's hands, the fingertips of volunteers were inoculated with a nonpathogenic strain of E. coli; these volunteers then pressed the inoculum onto sterile paper swatches. Another group of volunteers whose hands had been moistened pressed their fingertips onto the contaminated paper swatches. Bacteria transferred to the moistened fingertips were cultivated according to standard laboratory procedures. RESULTS: The four tested organisms showed differences in length of survival depending on environmental room conditions, but were stable on paper for up to 72 hours and still cultivable after seven days. Test organisms were transferred to paper, survived on it, and were retransferred back to hands. CONCLUSION: Paper can serve as a vehicle for cross-contamination of bacterial pathogens in medical settings if current recommendations on hand hygiene aren't meticulously followed. PMID- 22082499 TI - Sarcopenic obesity: strategies for management. AB - OVERVIEW: Sarcopenia is the age-related loss of muscle mass. Sarcopenic obesity, which describes the process of muscle loss combined with increased body fat as people age, is associated with loss of strength and function, reduced quality of life, and early death. This article describes the clinical significance of sarcopenia and sarcopenic obesity, their pathophysiology, and management strategies for healthy older adults. Both diet and exercise are essential for preventing and reversing loss of muscle and gains in fat. Dietary approaches include protein supplementation and a high protein diet. Exercise strategies promote resistance training in order to maintain muscle mass and maximize energy expenditure. Nurses should be knowledgeable about this condition and its management and routinely educate older patients on the benefits of resistance training and dietary protein to prevent or reverse sarcopenia and sarcopenic obesity. PMID- 22082500 TI - Management of distressing procedures in children and young people: time to adhere to the guidelines. PMID- 22082501 TI - Competent for confidence at 12 years of age? PMID- 22082502 TI - Complete thoracic myelocystocele: a rare benign spinal dysraphism with clinical significance. PMID- 22082503 TI - Survey of undergraduate sleep medicine teaching in UK medical schools. PMID- 22082504 TI - Zinc finger nuclease and homing endonuclease-mediated assembly of multigene plant transformation vectors. AB - Binary vectors are an indispensable component of modern Agrobacterium tumefaciens mediated plant genetic transformation systems. A remarkable variety of binary plasmids have been developed to support the cloning and transfer of foreign genes into plant cells. The majority of these systems, however, are limited to the cloning and transfer of just a single gene of interest. Thus, plant biologists and biotechnologists face a major obstacle when planning the introduction of multigene traits into transgenic plants. Here, we describe the assembly of multitransgene binary vectors by using a combination of engineered zinc finger nucleases (ZFNs) and homing endonucleases. Our system is composed of a modified binary vector that has been engineered to carry an array of unique recognition sites for ZFNs and homing endonucleases and a family of modular satellite vectors. By combining the use of designed ZFNs and commercial restriction enzymes, multiple plant expression cassettes were sequentially cloned into the acceptor binary vector. Using this system, we produced binary vectors that carried up to nine genes. Arabidopsis (Arabidopsis thaliana) protoplasts and plants were transiently and stably transformed, respectively, by several multigene constructs, and the expression of the transformed genes was monitored across several generations. Because ZFNs can potentially be engineered to digest a wide variety of target sequences, our system allows overcoming the problem of the very limited number of commercial homing endonucleases. Thus, users of our system can enjoy a rich resource of plasmids that can be easily adapted to their various needs, and since our cloning system is based on ZFN and homing endonucleases, it may be possible to reconstruct other types of binary vectors and adapt our vectors for cloning on multigene vector systems in various binary plasmids. PMID- 22082505 TI - MYB8 controls inducible phenolamide levels by activating three novel hydroxycinnamoyl-coenzyme A:polyamine transferases in Nicotiana attenuata. AB - A large number of plants accumulate N-acylated polyamines (phenolamides [PAs]) in response to biotic and/or abiotic stress conditions. In the native tobacco (Nicotiana attenuata), the accumulation of two major PAs, caffeoylputrescine and dicaffeoylspermidine (DCS), after herbivore attack is known to be controlled by a key transcription factor, MYB8. Using a broadly targeted metabolomics approach, we show that a much larger spectrum of PAs composed of hydroxycinnamic acids and two polyamines, putrescine and spermidine, is regulated by this transcription factor. We cloned several novel MYB8-regulated genes, annotated as putative acyltransferases, and analyzed their function. One of the novel acyltransferases (AT1) is shown to encode a hydroxycinnamoyl-coenzyme A:putrescine acyltransferase responsible for caffeoylputrescine biosynthesis in tobacco. Another gene (acyltransferase DH29), specific for spermidine conjugation, mediates the initial acylation step in DCS formation. Although this enzyme was not able to perform the second acylation toward DCS biosynthesis, another acyltransferase gene, CV86, proposed to act on monoacylated spermidines, was isolated and partially characterized. The activation of MYB8 in response to herbivore attack and associated signals required the activity of LIPOXYGENASE3, a gene involved in jasmonic acid (JA) biosynthesis in N. attenuata. These new results allow us to reconstruct a complete branch in JA signaling that defends N. attenuata plants against herbivores: JA via MYB8's transcriptional control of AT1 and DH29 genes controls the entire branch of PA biosynthesis, which allows N. attenuata to mount a chemically diverse (and likely efficient) defense shield against herbivores. PMID- 22082507 TI - Involvement of sensory neurons in bone defect repair in rats. AB - We investigated bone repair in sensory-denervated rats, compared with controls, to elucidate the involvement of sensory neurons. Nine-week-old male Wistar rats received subcutaneous injections of capsaicin to denervate sensory neurons. Rats treated with the same amount of vehicle served as controls. A standardized bone defect was created on the parietal bone. We measured the amount of repaired bone with quantitative radiographic analysis and the mRNA expressions of osteocalcin and cathepsin K with real-time polymerase chain reaction (PCR). Quantitative radiographic analysis showed that the standard deviations and coefficients of variation for the amount of repaired bone were much higher in the capsaicin treated group than in the control group at any time point, which means that larger individual differences in the amount of repaired bone were found in capsaicin-treated rats than controls. Furthermore, radiographs showed radiolucency in pre-existing bone surrounding the standardized defect only in the capsaicin-treated group, and histological observation demonstrated some multinuclear cells corresponding to the radiolucent area. Real-time PCR indicated that there was no significant difference in the mRNA expression levels of osteocalcin and cathepsin K between the control group and the capsaicin-treated group. These results suggest that capsaicin-induced sensory denervation affects the bone defect repair. PMID- 22082506 TI - Nucleoli: composition, function, and dynamics. PMID- 22082508 TI - Husbandry risk factors associated with subclinical coccidiosis in young cattle. AB - This paper describes an observational longitudinal study of cattle farms in England and Wales, which aimed to identify management practices associated with the presence of Eimeria spp. infection in young cattle. Thirty cattle farms situated in England and Wales were selected and one group of more than 20 young cattle aged 5-18 months of age was monitored on each farm. Three variables were identified as significantly associated with status in a multivariable model. The odds of finding Eimeria spp. were lower on farms that kept sheep on the same premises as the cattle, as was an increase in the maximum age within the sampled group. The latter probably reflects the development of post-infection immunity within the sampled animals. Good water-trough hygiene protected against Eimeria spp. oocyst excretion, with the odds of detection being higher on farms where it was reported that the water troughs were not cleaned and emptied more than once per month. The value of frequent emptying and cleaning of water troughs in reducing the exposure of calves to Eimeria spp. and thus lowering the impact of coccidiosis, both clinical and subclinical should be communicated to cattle farmers. PMID- 22082509 TI - Gait analysis using 3D accelerometry in horses sedated with xylazine. AB - The aim of the present study was to verify the efficacy and sensitivity of an accelerometric device in detecting and quantifying the degree of movement alteration produced in horses sedated with xylazine. Horses (n=6) were randomly administered either xylazine or a control by intravenous injection, with at least 1 week between each treatment. A triaxial accelerometric device was used for the accelerometric gait assessment 15 min before (baseline) and 5, 15, 30, 45, 60, 75, 90, 105 and 120 min after each treatment. Eight different accelerometric parameters were calculated, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsion power, mediolateral power and total power, with the force of acceleration and the dorsoventral, mediolateral and craniocaudal (propulsive) parts of the power then calculated. Administration of xylazine decreased many of the parameters investigated, with significant differences for speed, stride frequency, dorsoventral power, propulsion power and total power at 5, 15, 30 and 45 min after injection. There were no significant differences in stride length values at any time point. Decreases in regularity values were evident with significant differences at every time point from 5 to 120 min following xylazine injection. Force values were also significantly reduced from 5 to 30 min after treatment and a redistribution of the total power was observed 5 min after injection as the mediolateral power increased significantly, while the dorsoventral power decreased. Accelerometry offers a practical, accurate, easy to use, portable and low cost method of objectively monitoring gait abnormalities at the walk in horses after sedation with xylazine. PMID- 22082510 TI - Preparation of 2-amino-2-C-glycosyl-acetonitriles from C-glycosyl aldehydes by Strecker reaction. AB - Synthesis of new 2-amino-2-C-D-glycosyl-acetonitriles in a Strecker reaction from various C-glycosyl aldehydes, chiral amines, and HCN was carried out. While aminonitriles from glycal and 2-deoxy-beta-D-glycosyl aldehydes were prepared in satisfactory yields, lower yields were obtained with C-glycosyl aldehydes. Strecker reaction with the benzyl-protected 1-C-formyl-D-galactal and S- or R-1 phenylethylamine (S-PEA or R-PEA) yielded predominantly the R-configured C glycosyl aminoacetonitrile. The direction of the nucleophilic addition appears to be governed by the configuration of the anomeric carbon with beta-linked sugars. Since the stereochemistry of the transition state is unknown according to the configuration of the major product a Felkin-Ahn selectivity can be mainly presumed. PMID- 22082511 TI - Novel in situ product removal technique for simultaneous production of propionic acid and vitamin B12 by expanded bed adsorption bioreactor. AB - A new type of in situ product removal (ISPR) technique of expanded bed adsorption (EBA) bioreactor was studied to simultaneously produce extracellular propionic acid and intracellular vitamin B12 by Propionibacterium freudenreichii CICC 10019. Resin screening experiments showed that the ZGA330 resin have the best biocompatibility and highest adsorption for propionic acid. Through the EBA bioreactor, propionic acid could be recovered efficiently by semi-continuous recirculation of the unfiltered broth, which eliminated the feedback inhibition of propionic acid. Fed-batch fermentation was carried out using the EBA system, resulting in a propionic acid concentration of 52.5 g L(-1) and vitamin B12 concentration of 43.04 mg L(-1) at 160 h, which correspond to product yields of 0.66 g g(-1) and 0.54 mg g(-1), respectively. The present study suggests that the EBA bioreactor can be utilized for the simple and economical production of propionic acid and vitamin B12 in a single fermentation process. PMID- 22082512 TI - A microwave reactor for characterization of pyrolyzed biomass. AB - A microwave reactor (MWR) was designed to investigate microwave-induced pyrolysis of biomass. Condensation of tars on the quartz reactor and the pipelines was prevented by an electric heating device, and a temperature control function allowed determination of product characteristics at constant temperatures. Temperature had an important influence on microwave pyrolysis; the yields of gas products increased from 17.69 wt.% to 22.27 wt.% and the ratio of combustible gas to total gas products increased from 67.21 vol.% to 77.14 vol.% as the temperature increased from 400 degrees C to 600 degrees C. A large number of volatiles was released as temperature increased, resulting in an increase in the number of pores of the coke and a uniform pore structure was obtained. The specific surface area of coke increased from 0.89 m(2)/g (400 degrees C) to 9.81m(2)/g (600 degrees C) and the pore volume increased from 0.006 cm(3)/g (400 degrees C) to 0.012 cm(3)/g (600 degrees C), but the average pore size decreased from 282.16 nm (400 degrees C) to 46.64 nm (600 degrees C). PMID- 22082513 TI - Venous thromboembolism prophylaxis in critically ill patients. AB - Venous thromboembolism (VTE) is a frequent but often silent complication of critical illness that has a negative impact on patient outcomes. The prevention of VTE is an essential component of patient care in the intensive care unit (ICU) setting, and is the focus of this article. The use of anticoagulant thromboprophylaxis significantly decreases the risk of VTE in ICU patients and is discussed at length. PMID- 22082514 TI - Vena cava interruption. AB - Anticoagulation has been proven to be effective in preventing and treating deep vein thrombosis and pulmonary embolus. However, many critically ill patients are unable to receive anticoagulation or suffer recurrent venous thromboembolism despite adequate treatment. This article examines the use of vena cava filters in the critically ill. Indications for, techniques, and complications of vena cava filter insertion are reviewed. The importance of vena cava filters with the option to be retrieved and bedside insertion in the intensive care unit is emphasized. PMID- 22082515 TI - Heparin-induced thrombocytopenia in critically ill patients. AB - Critically ill patients commonly evince thrombocytopenia, either evident on admission to the intensive care unit (ICU) or that develops during their stay. Heparin-induced thrombocytopenia (HIT) explains thrombocytopenia in only approximately 1/100 critically ill patients; also, only 1 or 2 in 10 ICU patients with a positive PF4-dependent enzyme immunoassay has "true" HIT. Thus, there is major potential for overdiagnosis of HIT in the ICU. A recent study showing that dalteparin is associated with a reduced frequency of HIT indicates that critically ill patients too can benefit from the HIT-reducing potential of this low molecular weight heparin preparation. PMID- 22082516 TI - Treatment of pulmonary embolism: anticoagulation, thrombolytic therapy, and complications of therapy. AB - During the last two decades, considerable progress in technology and clinical research methods have led to advances in the approach to the diagnosis, prevention, and treatment of acute venous thromboembolism (VTE). Despite this, however, the diagnosis is often delayed and preventive methods are often ignored. Thus, the morbidity and mortality associated with VTE remain high. The therapeutic approach to acute VTE is discussed in this article, with a particular focus on the intensive care unit setting. PMID- 22082517 TI - Diagnostic approach to deep venous thrombosis and pulmonary embolism in the critical care setting. AB - Considerable progress has been made during the last 30 years in the prevention, diagnosis, and therapy of venous thromboembolism. This article discusses the epidemiology, pathophysiology, and clinical presentation of the disease as well as the diagnostic uncertainty that exists in the critical care setting. Diagnostic approaches for deep venous thrombosis and pulmonary embolism are considered, including clinical prediction rules, D-dimer, contrast venography, duplex ultrasonography, computed tomographic angiography and venography, magnetic resonance imaging, ventilation-perfusion scanning, chest radiograph, arterial blood gases, electrocardiography, and echocardiography. PMID- 22082518 TI - Natural history of venous thromboembolism. AB - Venous thromboembolism (VTE) originates in systemic venous thrombosis and has different etiological mechanisms and natural history from arterial thrombosis. VTE typically originates as deep venous thrombosis in a lower extremity, where it may give rise to acute symptoms "upstream" from the obstructed vein, result in pulmonary embolism, and/or cause chronic venous obstruction. Pulmonary embolism may result in acute respiratory symptoms, cardiovascular collapse and, uncommonly, may also cause chronic disease. PMID- 22082519 TI - Major pulmonary embolism. AB - The scope and spectrum of pulmonary embolism (PE) that are likely to challenge the intensivist are dominantly confined to 2 scenarios; first, a patient presenting with undifferentiated shock or respiratory failure and, second, an established intensive care unit (ICU) or hospital patient who develops hemodynamically unstable PE after admission. In either scenario, the diagnostic approach and therapeutic options are challenging. Differentiating PE from other life-threatening cardiopulmonary disorders can be exceedingly difficult. This article will review a structured pathophysiologic approach to the diagnostic, resuscitative and management strategies related to PE in the ICU. PMID- 22082520 TI - Epidemiology and incidence: the scope of the problem and risk factors for development of venous thromboembolism. AB - The proportion of hospitalized patients with pulmonary embolism (PE) is increasing. Whether this represents more admissions with PE or more diagnoses made in hospitalized patients is uncertain. The proportion of hospitalized patients with deep venous thrombosis has decreased precipitously as a result of home treatment. Asians and Native Americans have a lower incidence of PE than whites or African Americans. The incidence of PE increases exponentially with age, but no age group, including infants and children, is immune. Several medical illnesses have now been shown to be associated with a higher risk for venous thromboembolism. Epidemiologic data and new information on risk factors provide insight into making an informed clinical assessment and evaluation for antithrombotic prophylaxis. PMID- 22082521 TI - Hypercoagulable states. AB - Hypercoagulable states can be inherited or acquired. Inherited hypercoagulable states can be caused by a loss of function of natural anticoagulant pathways or a gain of function in procoagulant pathways. Acquired hypercoagulable risk factors include a prior history of thrombosis, obesity, pregnancy, cancer and its treatment, antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and myeloproliferative disorders. Inherited hypercoagulable states combine with acquired risk factors to establish the intrinsic risk of venous thromboembolism for each individual. Venous thromboembolism occurs when the risk exceeds a critical threshold. Often a triggering factor, such as surgery, pregnancy, or estrogen therapy, is required to increase the risk above this critical threshold. PMID- 22082522 TI - Mortality risk assessment and the role of thrombolysis in pulmonary embolism. AB - Acute venous thromboembolism remains a frequent disease, with an incidence ranging between 23 and 69 cases per 100,000 population per year. Of these patients, approximately one-third present with clinical symptoms of acute pulmonary embolism (PE) and two-thirds with deep venous thrombosis (DVT). Recent registries and cohort studies suggest that approximately 10% of all patients with acute PE die during the first 1 to 3 months after diagnosis. Overall, 1% of all patients admitted to hospitals die of acute PE, and 10% of all hospital deaths are PE-related. These facts emphasize the need to better implement our knowledge on the pathophysiology of the disease, recognize the determinants of death or major adverse events in the early phase of acute PE, and most importantly, identify those patients who necessitate prompt medical, surgical, or interventional treatment to restore the patency of the pulmonary vasculature. PMID- 22082523 TI - Venous thromboembolism in critical care. PMID- 22082524 TI - When age is irrelevant: distractor inhibition and target activation in priming of pop-out. AB - OBJECTIVES: Recent research suggests that inhibition at early stages of visual processing may be age invariant. We test this proposal using a priming of pop-out (PoP) measure developed by Lamy, Antebi, Aviani, and Carmel (2008. Priming of pop out provides reliable measures of target activation and distractor inhibition in selective attention. Vision Research, 48, 30-41. doi:10.1016/j.visres.2007.10.009). In PoP, a unique item, which visually "pops out" in a field of distractors, grabs our attention faster when its defining feature (e.g., color red) repeats across trials and slower when distractor- and target-defining features switch between trials. Here, we explore whether the processes underlying PoP, which prevent access to distractors and facilitate access to the singleton, remain intact with age. METHOD: Participants faced a display of circles and judged the direction of a letter T inscribed within a uniquely colored circle. RESULTS: All underlying components of PoP were present in older and younger adults. Participants revealed distractor inhibition by responding faster to a color singleton when the color of surrounding distractors repeated and slower when the singleton assumed the color of distractors from the previous trial. DISCUSSION: Our findings suggest that the inhibitory processes underlying PoP remain intact with age. PMID- 22082525 TI - Corrosion in drinking water pipes: the importance of green rusts. AB - Complex crystallographic composition of the corrosion products is studied by diffraction methods and results obtained after different pre-treatment of samples are compared. The green rusts are found to be much more abundant in corrosion scales than it has been assumed so far. The characteristic and crystallographic composition of corrosion scales and deposits suspended in steady waters were analyzed by X-ray diffraction (XRD). The necessity of the examination of corrosion products in the wet conditions is indicated. The drying of the samples before analysis is shown to substantially change the crystallographic phases originally present in corrosion products. On sample drying the unstable green rusts is converted into more stable phases such as goethite and lepidocrocite, while the content of magnetite and siderite decreases. Three types of green rusts in wet materials sampled from tubercles are identified. Unexpectedly, in almost all corrosion scale samples significant amounts of the least stable green rust in chloride form was detected. Analysis of corrosion products suspended in steady water, which remained between tubercles and possibly in their interiors, revealed complex crystallographic composition of the sampled material. Goethite, lepidocrocite and magnetite as well as low amounts of siderite and quartz were present in all samples. Six different forms of green rusts were identified in the deposits separated from steady waters and the most abundant was carbonate green rust GR(CO(3)(2-))(I). PMID- 22082526 TI - Novel magnetically induced membrane vibration (MMV) for fouling control in membrane bioreactors. AB - Conventional submerged membrane bioreactors (MBRs) rely on the coarse bubbles aeration to generate shear at the liquid-membrane interface to limit membrane fouling. Unfortunately, it is a very energy consuming method, still often resulting in a rapid decrease of membrane permeability and consequently in higher expenses. In this paper, the feasibility of a novel magnetically induced membrane vibration (MMV) system was studied in a lab-scale MBR treating synthetic wastewater. The effects on membrane fouling of applied electrical power of different operation strategies, of membrane flux and of the presence of multiple membranes on one vibrating engine on membrane fouling were investigated. The filtration performance was evaluated by determining the filtration resistance profiles and critical flux. The results showed clear advantages of the vibrating system over conventional MBR processes by ensuring higher fluxes at lower fouling rates. Intermittent vibration was found a promising strategy for both efficient fouling control and significant energy saving. The optimised MMV system is presumed to lead to significant energy and cost reduction in up-scaled MBR operations. PMID- 22082527 TI - Reverse osmosis concentrate treatment via a PAC-MF accumulative countercurrent adsorption process. AB - Organic pollutants in reverse osmosis (RO) concentrates from wastewater reclamation are mainly comprised of low molecular weight biorefractory compounds. Generally, advanced oxidation methods for oxidizing these organics require a relatively high level of energy consumption. In addition, conventional adsorption removal methods require a large dose of activated carbon. However, the dose can be reduced if its full adsorption capacity can be used. Therefore, the combined technology of powdered activated carbon (PAC) adsorption and microfiltration (MF) membrane filtration was studied to develop a countercurrent two-stage adsorption process. A PAC accumulative adsorption prediction method was proposed based on the verification of a PAC multi-stage adsorption capacity equation. Moreover, the prediction method was amended for a more accurate prediction of the effluent quality because adsorption isotherm constants were affected by the initial adsorbate concentration. The required PAC dose for the accumulative countercurrent two-stage adsorption system was 0.6 g/L, whereas that of the conventional adsorption process was 1.05 g/L when the dilution factor(F) was 0.1 and the COD and DOC removal rates were set to 70% and 68.1%, respectively. Organic pollutants were satisfactorily removed with less consumption of PAC. Effluent from this combined technology can be further reclaimed by an RO process to improve the overall recovery rate to between 91.0% and 93.8% with both economic and environmental benefits. PMID- 22082528 TI - A model for predicting resuspension of Escherichia coli from streambed sediments. AB - To improve the modeling of water quality in watersheds, a model is developed to predict resuspension of Escherichia coli from sediment beds in streams. The resuspension rate is expressed as the product of the concentration of E. coli attached to sediment particles and an erosion rate adapted from work on sediment transport. The model uses parameter values mostly taken from previous work, and it accounts for properties of the flow through the bottom shear stress and properties of the sediment through the critical shear stresses for cohesive and non-cohesive sediment. Predictions were compared to resuspension rates inferred from a steady mass balance applied to measurements at sixteen locations in a watershed. The model's predictions matched the inferred rates well, especially when the diameter of particles to which E. coli attach was allowed to depend on the bottom shear stress. The model's sensitivity to the parameters depends on the contributions of particle packing and binding effects of clay to the critical shear stress. For the current data set, the uncertainty in the predictions is controlled by the concentration of E. coli attached to sediment particles and the slope used to estimate the bottom shear stress. PMID- 22082529 TI - Down-regulation of mitogen-inducible gene 6, a negative regulator of EGFR, enhances resistance to MEK inhibition in KRAS mutant cancer cells. AB - Previously, we found that KRAS mutant cancer cells showed variable response to AZD6244, a MEK inhibitor through differential activation of EGFR/AKT. To investigate its mechanism, we performed cDNA microarray using four KRAS mutant cancer cells. We found that treatment with AZD6244 reduced the expression of mitogen-inducible gene 6 (MIG6), a negative feedback regulator for EGFR, in AZD6244-resistant cells, while activity of EGFR and AKT was increased in these cells. Reconstitution or knockdown of MIG6 expression affected cancer cell responses to AZD6244. Treatment with a combination of EGFR inhibitor and AZD6244 inhibited cell proliferation synergistically without activation of AKT in AZD6244 resistant cells. Our study provides a mechanism of differential response to MEK inhibition in KRAS mutant cancer. PMID- 22082530 TI - DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol induced cell growth and restores expression of DNA repair genes in human breast cancer cells. AB - Prolonged exposure to elevated levels of estrogen is a risk factor for breast cancer. Though increased cell growth and loss of DNA repair capacity is one of the proposed mechanisms for estrogen-induced cancers, the mechanism through which estrogen induces cell growth and decreases DNA repair capacity is not clear. DNA hypermethylation is known to inactivate DNA repair genes and apoptotic response in cancer cells. Therefore, the objective of this study was to determine the role of DNA hypermethylation in estrogen-induced cell growth and regulation of DNA repair genes expression in breast cancer cells. To achieve this objective, the estrogen-responsive MCF-7 cells either pretreated with 5-aza-2-deoxycytidine (5 aza-dC) or untreated (as control) were exposed to 17 beta-estradiol (E2), and its effect on cell growth and expression of DNA repair genes were measured. The result revealed that 5-aza-dC abrogates the E2-induced growth in MCF-7 cells. An increased expression of OGG1, MSH4, and MLH1 by 5-aza-dC treatment alone, suggest the DNA hypermethylation as a potential cause for decreased expression of these genes in MCF-7 cells. The decreased expression of ERCC1, XPC, OGG1, and MLH1 by E2 alone and its restoration by co-treatment with 5-aza-dC further suggest that E2 reduces the expression of these DNA repair genes potentially through promoter hypermethylation. Reactivation of mismatch repair (MMR) gene MLH1 and abrogation of E2-induced cell growth by 5-aza-dC treatment suggest that estrogen causes increased growth in breast cancer cells potentially through the inhibition of MMR mediated apoptotic response. In summary, this study suggests that estrogen increases cell growth and decreases the DNA repair capacity in breast cancer cells, at least in part, through epigenetic mechanism. PMID- 22082531 TI - Anomalous diffusion and memory effects on the impedance spectroscopy for finite length situations. AB - The contribution of ions to the electrical impedance of an electrolytic cell limited by perfect blocking electrodes is determined by considering the role of the anomalous diffusion process and memory effects. Analytical solutions for fractional diffusion equations together with Poisson's equation relating the effective electric field to the net charge density are found. This procedure allows the construction of general expressions for the electrochemical impedance satisfying the Kramers-Kronig relations when the diffusion of ions in the cell is characterized by the usual, as well as by anomalous, behavior. PMID- 22082532 TI - Forgiveness results from integrating information about relationship value and exploitation risk. AB - Exploitation is a fact of life for social organisms, and natural selection gives rise to revenge mechanisms that are designed to deter such exploitations. However, humans may also possess cognitive forgiveness mechanisms designed to promote the restoration of valuable social relationships following exploitation. In the current article, the authors test the hypothesis that decisions about forgiveness result from a computational system that combines information about relationship value and exploitation risk to produce decisions about whom to forgive following interpersonal offenses. The authors examined the independent and interactive effects of relationship value and exploitation risk across two studies. In Study 1, controlling for other constructs related to forgiveness, the authors assessed relationship value and exploitation risk. In Study 2, participants experienced experimental manipulations of relationship value and exploitation risk. Across studies, using hypothetical and actual offenses and varied forgiveness measures, the combination of low exploitation risk and high relationship value predicted the greatest forgiveness. PMID- 22082533 TI - Computed tomography and magnetic resonance features of gliosarcoma: a study of 54 cases. AB - OBJECTIVE: To investigate the features of pathologically confirmed gliosarcomas using computed tomography (CT) and magnetic resonance (MR) imaging. METHODS: We retrospectively reviewed the cross-sectional CT and MR images of 54 patients (37 males and 17 females; mean age, 44.5 years; range, 13-74 years) with gliosarcomas confirmed by histopathology. RESULTS: Across all patients, there were 59 lesions. On nonenhanced CT and MR images, tumors were predominantly inhomogeneous. On the postcontrast CT and MR images, 50 (84.7%) irregular lesions had thick walls with a strong rim- and ringlike enhancement, whereas the remaining 9 (15.3%) round or oval lesions had even thin walls with an enhanced peripheral ring. Magnetic resonance spectroscopy showed increased choline and lactate values, along with decreased N-acetylaspartate and creatine values. On diffusion-weighted imaging, the tumor was slightly or markedly hyperintense compared with the white matter. CONCLUSION: A well-demarcated mass located peripherally, with rimlike or ring enhancement, is a common presentation of gliosarcoma on CT and MR images. In addition, magnetic resonance spectroscopy and diffusion-weighted imaging can be used to make a differential diagnosis. PMID- 22082534 TI - Dilated dysplastic vestibule: a new computed tomographic finding in patients with large vestibular aqueduct syndrome. AB - OBJECTIVE: Large vestibular aqueduct syndrome (LVAS) is one of the most common anomalies of the inner ear. The purpose of our study was to evaluate the vestibule for associated aberrations. In particular, we assessed the vestibular volume in patients with LVAS, compared it to an age-matched control population, and evaluated the relationship between the size of the vestibular aqueduct and the vestibule. METHODS: We reviewed studies of high-resolution computed tomography of temporal bone of 24 consecutive patients with LVAS (15 girls and 9 boys; average age, 8.1 years). Of these, 21 patients had bilateral LVAS and 3 patients had unilateral LVAS. Each ear was evaluated for the size of the vestibular aqueduct and the volume of the vestibule. Similar measurements were obtained in an age-matched control population (28 girls and 18 boys; average age, 8.3 years). RESULTS: The volume of the vestibule was found to be significantly enlarged in patients with LVAS compared to the control population (right ear, P < 0.0001; left ear, P < 0.0001). A linear correlation could be established between an enlarged vestibular aqueduct and corresponding increase in the volume of the vestibule (right side, P < 0.01; left side, P < 0.01). CONCLUSION: A dilated dysplastic vestibule is a consistently associated finding in patients with LVAS. PMID- 22082535 TI - Diagnostic usefulness of 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography in recurrent brain tumor. AB - OBJECTIVE: We evaluated the diagnostic usefulness of 3'-deoxy-3' [F]fluorothymidine (FLT) compared with 2-[F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in recurrent brain tumors. METHODS: Twenty patients with suspected recurrence after surgical removal of primary tumors were studied. The uptake was assessed visually and quantified by standardized uptake value (SUV) and SUV ratio of tumor to white matter, tumor to gray matter, and tumor to normal tissue. Final diagnoses were made by histopathology or clinical and radiological follow-up. RESULTS: Of 20 lesions, 15 were recurrences. 3'-Deoxy 3'-[F]fluorothymidine PET showed high diagnostic sensitivity (15/15 [100%]) and moderate specificity (3/5 [60.0%]). 2-[F]fluoro-2-deoxy-D-glucose PET showed moderate diagnostic sensitivity (11/15 [73.3%]) and specificity (4/5 [80%]). All of 4 recurrent tumors without FDG uptake showed FLT uptake. Tumor-to-normal tissue ratios (3.99 +/- 1.72) of recurrent tumors on FLT PET were significantly higher than tumor-to-white matter ratios (1.96 +/- 0.93) and tumor-to-gray matter ratios (1.32 +/- 0.33) on FDG PET (P < 0.001), although SUVs (0.62 +/- 0.32) of recurrent tumors on FLT PET were lower than those (2.44 +/- 1.02) on FDG PET (P < 0.001). CONCLUSION: 3'-Deoxy-3'-[F]fluorothymidine PET has a high sensitivity but a lower specificity, which has a limited role in the diagnosis of recurrent brain tumors as a complimentary tool of magnetic resonance imaging. PMID- 22082536 TI - Fetal MR imaging of constriction band syndrome involving the skull and brain. AB - We present here the case of a fetus with constriction band syndrome involving the skull and brain. Whereas prenatal ultrasound did not show direct signs of this condition, fetal magnetic resonance imaging (MRI) revealed it clearly. This may be the first case of constriction band syndrome to be diagnosed using fetal MRI. As a supplementary tool, fetal MRI may lead to an accurate diagnosis when prenatal ultrasound presents equivocal findings with respect to central nervous system development. PMID- 22082537 TI - Subarcuate artery and canal: an important anatomic variant. AB - An aberrant subarcuate artery and its related canal are rare. The presence of this variation has a surgical significance, that is, risk of hemorrhage, if accidentally nicked. It is therefore important to be aware of this entity, and its relative anatomy, to avoid any untoward complication. We present a case of a 29-year-old man who presented with hearing loss after trauma. High-resolution computed tomographic scan of the temporal bone demonstrated an enlarged subarcuate canal. PMID- 22082538 TI - Liver metastases from colorectal cancer treated with conventional and antiangiogenetic chemotherapy: evaluation with liver computed tomography perfusion and magnetic resonance diffusion-weighted imaging. AB - OBJECTIVE: The objectives of the study were to determine whether perfusion computed tomography (CT-p) and magnetic resonance diffusion-weighted imaging (MR DWI) can allow evaluation of the effects of chemotherapy combined with antiangiogenetic treatment on liver metastases in patients with advanced colorectal cancer and to determine if changes in CT-p and MR-DWI correlate with the response to therapy as assessed by conventional Response Evaluation Criteria in Solid Tumors (RECIST). METHODS: Eighteen patients with liver metastases from colorectal cancer underwent CT-p and MR-DWI before and 6 months after chemotherapy and antiangiogenetic treatment. Lesions were classified according to RECIST criteria (complete response [CR], partial response [PR], stable disease [SD], and progressive disease) and calculations of CT-p parameters including blood flow (BF), blood volume (BV), capillary permeability (CP), and MR-DWI apparent diffusion coefficient (ADC) values were performed; RECIST, CT-p, and MR DWI measurements at baseline and follow-up were tested for statistically significant differences using the paired-samples t test. Baseline and follow-up perfusion parameters of the lesions were also compared on the basis of therapy response assessed by RECIST criteria using independent-samples t test. P < 0.05 was considered indicative of a statistically significant difference for all statistical test. RESULTS: Six patients (6/18; 33.3%) were classified as PR (), and the remaining 12 (12/18; 66.7%) were classified as SD. On a per-lesion basis, 2 (2/32; 6.3%) cannot be identified at follow-up, 6 (6/32; 18.8%) showed a decrease in size of more than 30%, and 24 (24/32; 75%) were substantially stable in size. No cases of progressive disease were demonstrated at follow-up. No statistically significant differences were demonstrated between PR, CR, and SD lesions for BF (P = 0.19), BV (P = 0.14), and ADC (P = 0.68) measurements, whereas CP was significantly higher in CR and PR lesions (P = 0.038). Considering differences between baseline and follow-up values, no statistically significant differences were noted between PR and CR lesions versus SD lesions for CT-p values (BF: P = 0.77; BV: P = 0.15; CP: P = 0.64). A statistically significant difference between PR and CR lesions and SD lesions was noted for ADC values (P = 0.047). CONCLUSION: Both CT-p and MR-DWI can detect therapy-induced modifications in lesion vascularization before significant changes in size are evident. PMID- 22082539 TI - Three-phase helical computed tomographic findings of hepatic neuroendocrine tumors: pathologic correlation with revised WHO classification. AB - OBJECTIVE: To evaluate 3-phase helical computed tomographic (CT) findings of hepatic neuroendocrine tumors and to correlate them with pathologic diagnoses based on the revised World Health Organization classification. METHODS: Over a 14 year period, we collected 38 patients with pathologically proven neuroendocrine tumors of the liver, either primary or metastatic, who had 3-phase helical CT scans. CT findings were evaluated for the morphologic and enhancement patterns (ie, hepatocellular carcinomalike, cholangiocarcinomalike, and combined patterns), and correlated those with pathologic diagnoses. RESULTS: The morphologic patterns were variable regardless of the pathologic diagnoses, except necrosis (P = 0.024). For the enhancement pattern, almost half of the tumors showed hepatocellular carcinomalike pattern, and the other half showed cholangiocarcinomalike or combined patterns, without correlation between the enhancement pattern and pathologic diagnoses (P = 0.402). CONCLUSIONS: The CT features of hepatic neuroendocrine tumors were variable and did not correlate with their pathologic diagnoses. However, hepatic neuroendocrine tumors frequently show hepatocellular carcinomalike arterial enhancement, and often show cholangiocarcinomalike delayed enhancement. PMID- 22082540 TI - Evaluation of the maximum depth of intraluminal appendiceal fluid to diagnose appendicitis with a 64-detector row CT scanner. AB - OBJECTIVE: The objective of this study was to investigate whether the criterion "maximum depth of intraluminal appendiceal fluid greater than 2.6 mm" ("DEPTH >2.6 mm"), with the use of 64-detector row computed tomography, is useful to diagnose appendicitis. METHODS: We retrospectively evaluated 0.68-mm-thick images of 2894 intravenously enhanced abdominal-pelvic computed tomography using the following criteria: (1) appendiceal wall thickness greater than 3 mm, (2) appendiceal wall enhancement, (3) focal cecal wall thickening, (4) adjacent lymphadenopathy greater than 5 mm, (5) appendicolith, (6) periappendiceal inflammation, and (7) the new criterion, DEPTH >2.6 mm. Of the 2894 images, 1013 were classified into normal group (including 622 distended [diameter >6 mm] but normal appendices without adjacent lesions), modified group (235 distended normal appendices modified with adjacent lesions), proven-appendicitis group (82 operatively proven appendicitis cases), and clinical-appendicitis group (62 clinically certified appendicitis cases). RESULTS: The new criterion, DEPTH >2.6 mm, demonstrated both higher sensitivities and higher specificities in all groups (>90%), although this criterion showed lower specificities than some conventional criteria. In contrast, conventional criteria showed lower sensitivities or lower specificities (<60%) in one or more of these groups. CONCLUSIONS: DEPTH >2.6 mm is particularly useful for differentiating appendicitis from distended normal appendix. PMID- 22082541 TI - Can the patient with cirrhosis be imaged for hepatocellular carcinoma without gadolinium?: Comparison of combined T2-weighted, T2*-weighted, and diffusion weighted MRI with gadolinium-enhanced MRI using liver explantation standard. AB - PURPOSE: This study aimed to evaluate a non-gadolinium-enhanced magnetic resonance imaging (MRI) protocol including T2-weighted, T2*-weighted, and diffusion-weighted MRI sequences for identifying hepatocellular carcinoma (HCC) with liver explantation as the reference standard. Also, a stand-alone pre- and dynamic post-gadolinium-enhanced liver MRI data set was interpreted from the available patient data for relative comparison purposes. MATERIALS AND METHODS: A retrospective review identified 37 appropriately selected liver transplant patients who had had preoperative MRI. Two data sets were created from the MRI studies: (1) non-gadolinium-enhanced (including T2-weighted, T2*-weighted, and diffusion-weighted sequences) and (2) pre- and dynamic post-gadolinium-enhanced (3-dimensional T1-weighted gradient recalled echo) and were presented to 2 independent, blinded observers. A separate blinded observer assessed the pathologic results from liver explantation to establish the reference standard. RESULTS: On explant pathology, 21 of 37 patients had 31 HCC (mean [SD] largest diameter, 19 [9] cm; range, 7-40 mm). Per-lesion sensitivity of non-gadolinium enhanced MRI for identifying HCC was 52% (reader 1) and 55% (reader 2), and specificity was 90% (reader 1) and 88% (reader 2). Per-lesion sensitivity of the stand-alone pre- and dynamic post-gadolinium-enhanced MRI was 84% (reader 1) and 81% (reader 2), and specificity was 62% (reader 1) and 65% (reader 2). CONCLUSIONS: Non-gadolinium-enhanced MRI had a moderate sensitivity for HCC but had a high specificity. Although non-gadolinium-enhanced MRI cannot be recommended as a primary imaging approach for HCC, the results demonstrate the contribution of non-gadolinium-enhanced sequences to imaging of HCC. A non gadolinium-enhanced MRI protocol may have a diagnostic value when gadolinium cannot be administered. PMID- 22082542 TI - Computed tomographic cholangiography in living liver transplant donors: factors determining the degree of contrast enhancement. AB - OBJECTIVE: To determine factors affecting liver and bile duct contrast enhancement during computed tomographic cholangiography (CTC) in living-donor transplant candidates. METHODS: Forty-four candidates underwent preoperative triphasic CT followed by intravenous infusion of 20 mL of iodipamide for CTC. Body size indices and liver volume were correlated to parenchymal and biliary enhancement. Bile duct visibility was compared to duct enhancement. RESULTS: Poorly visualized first- and second-order bile ducts demonstrated diminished enhancement (P < 0.015). Both CTC parenchymal and biliary enhancement correlated inversely with body surface area, height, and weight (P < 0.001); inverse correlation was also seen between liver volume and parenchymal enhancement (P < 0.001). A moderately positive correlation was noted between CTC biliary and parenchymal portal venous enhancement (r = 0.421; P = 0.004). CONCLUSIONS: Computed tomographic cholangiography parenchymal and biliary enhancement diminishes with increased body size and liver volume, supporting a need for adjustable contrast dosing. Portal venous parenchymal enhancement may serve as a preinfusion indicator. PMID- 22082544 TI - Investigation of a logistic model for T2* dynamic susceptibility contrast magnetic resonance imaging (dscMRI) perfusion studies. AB - There are a number of T1- and T2-based dynamic contrast-enhanced magnetic resonance imaging pharmacokinetic modeling approaches to study cancer microvasculature. Alternatively, model-free approaches offer an easy, quantitative assessment of microcirculation. In this work, we investigate a 6 parameter model-free approach applied to a T2*-weighted echo-planar imaging bolus response curve. We tested this new approach on a small cohort of patients with clinically diagnosed primary rectal carcinoma before adjuvant chemoradiotherapy and surgical excision. Comparison with healthy muscle tissue shows that logistic parameters P1/P2, P4, and P5 offer good discrimination between tumor and healthy tissue. Bolus response logistic parameters P4 and P5 have been implicated in previous T1-based works as being important in the assessment of cancer malignancy. Further comparison of T2* parameters with signal attenuation amplitude (maximum signal drop) and percentage baseline signal loss also corroborates the models' ability to quantify the microenvironment. PMID- 22082543 TI - Clinical significance of the transitional phase at gadoxetate disodium-enhanced hepatic MRI for the diagnosis of hepatocellular carcinoma: preliminary results. AB - OBJECTIVES: To investigate the clinical significance of the "transitional phase" at gadoxetate disodium (Gd-EOB)-enhanced magnetic resonance imaging for diagnosing hepatocellular carcinoma (HCC). METHODS: We studied 54 patients with 70 histologically diagnosed HCC. Transitional- and hepatobiliary-phase (TP, HBP) images were acquired 3 and 20 minutes after Gd-EOB injection, respectively. Radiologists measured the size of the hepatic tumors on images and surgical specimens and qualitatively evaluated the signal intensity of the hepatic tumors during TP and HBP independently. RESULTS: In 4 patients with portal tumor embolism who had undergone percutaneous transhepatic portal embolization and who manifested arterioportal (AP) shunts, the low-intensity area was larger during HBP than TP. Of the 70 HCCs, 4 were of high signal intensity during HBP and 2 were of slightly low intensity during TP. CONCLUSION: Tumor extension seen during TP rather than HBP more accurately reflected histological findings in patients with HCC with portal tumor thrombi, percutaneous transhepatic portal embolization, or AP shunt. PMID- 22082545 TI - The prognostic value of vascular diameter measurements on routine chest computed tomography in patients not referred for cardiovascular indications. AB - OBJECTIVES: The aim of the study was to investigate whether diameter measurements of the thoracic aorta and the heart can be used as prognostic markers for future cardiovascular disease. METHODS: Following a case-cohort design, a total of 10,410 patients undergoing chest computed tomography were followed up for a mean period of 17 months. The ones with a cardiovascular indication were excluded. Diameter measurements were evaluated with Cox proportional hazard analysis. RESULTS: Five hundred fifteen incident cardiovascular events occurred during follow-up. The heart (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.03 1.06) and ascending thoracic (HR, 1.002; 95% CI, 1.001-1.004) diameter showed an exponential prognostic effect beyond a threshold diameter of, respectively, 11 and 30 mm; the descending aortic diameter (HR, 1.04; 95% CI, 1.01-1.13) and cardiothoracic ratio (HR, 1.06; 95% CI, 1.04-1.08) showed linear prognostic effects beyond, respectively, 25 and 0.45 mm. CONCLUSION: Intrathoracic diameter measurements can be used as markers to predict cardiovascular events in patients not referred for that disease outcome. PMID- 22082546 TI - Aortic endograft surveillance: use of fast-switch kVp dual-energy computed tomography with virtual noncontrast imaging. AB - OBJECTIVE: To assess endoleak detection and patients' radiation exposure using fast-switch peak kilovoltage (kVp) dual-energy computed tomography (DECT) with virtual noncontrast (VNC) imaging. METHODS: Institutional review board approved retrospective review of triphasic CTs for endograft follow-up: single-energy true noncontrast (TNC) and dual-energy arterial- and venous-phase postcontrast scans on GE HD-750 64-detector scanners. Iodine-subtracted VNC images generated from dual-energy data. Two radiologists (VNC readers) independently performed 2 reading sessions without TNC images: (1) arterial and VNC and (2) venous and VNC. Interrater agreement, leak detection sensitivity, and dose estimates were calculated. RESULTS: Original dictations described 24 endoleaks in 78 scans. Virtual noncontrast reader agreement was high (kappa = 0.78-0.79). Virtual noncontrast reader ranges for sensitivity and negative predictive value for leak detection were 87.5% to 95.8% and 94.0% to 98.0% in venous phase. Dose reduction estimate was 40% by eliminating one phase and 64% by eliminating 2 phases of imaging. CONCLUSION: Virtual noncontrast images from fast-switch peak kilovoltage DECT data can substitute for TNC imaging in the postendograft aorta, conferring substantial dose reduction. Eliminating 1 of 2 postcontrast phases further reduces dose, with greater negative predictive value for leak detection in the venous versus the arterial phase. Thus, the use of a monophasic venous-phase DECT with VNC images is suggested for long-term endograft surveillance in stable patients. PMID- 22082547 TI - Advanced adaptive axial-sequential prospectively electrocardiogram-triggered dual source coronary computed tomographic angiography in a patient with atrial fibrillation. AB - Atrial fibrillation is considered a relative contraindication to coronary computed tomographic angiography (CCTA) because image quality and radiation dose saving measures largely depend on low and stable heart rates. Most published experiences with CCTA during atrial fibrillation have relied on retrospective gating to mitigate artifacts via electrocardiogram editing. However, a large number of patients arrive at the CT suite with irregular heart rates. We present a case in which we used a prospectively electrocardiogram-triggered axial sequential scan mode with a novel arrhythmia protection algorithm to obtain motion-free, high-quality CCTA images at a low radiation dose. PMID- 22082548 TI - Use of dynamic phase subtraction (DPS) map in dynamic contrast-enhanced MRI of the breast. AB - BACKGROUND: The Breast Imaging Reporting and Data System (BI-RADS) of the American College of Radiology recommends careful examination of the region of interest (ROI) in areas that seem to show a washout pattern on time-intensity curve (TIC). However, it is difficult to identify malignancies because many benign lesions also show enhancement, and these include cysts, hemorrhage, fibrosis, and necrosis in the mass. PURPOSE: This study was performed to assess the performance of the dynamic phase subtraction (DPS) map for dynamic contrast enhanced magnetic resonance imaging (MRI) of the breast. A DPS map is a map image with pixel-by-pixel subtraction of an early-phase image from a delayed-phase image obtained in a dynamic study. MATERIALS AND METHODS: The use of the DPS map was analyzed retrospectively in 53 patients (32-84 years old) who underwent dynamic contrast-enhanced MRI of the breast. Sensitivity and specificity were compared with and without a DPS map for masses diagnosed as malignant lesions by biopsy. In addition, the patterns of time-intensity curves 30 seconds, 90 seconds, and 5 minutes after injection of contrast agent were compared with and without a DPS map. RESULTS: Sensitivity increased from 0.78 to 0.95, and specificity increased from 0.71 to 0.95 with reference to the DPS map. The pattern of TIC changed from continuous to a plateau in 9 cases, from a plateau to washout in 21 cases, and from continuous to washout in 7 cases. CONCLUSION: Use of the DPS map of dynamic contrast-enhanced MRI of the breast results in high detection rates of malignant masses, allows accurate ROI setting of TIC, and reduces operator's task. PMID- 22082549 TI - Internet-based videoconferencing and data collaboration for the imaging community. AB - Internet protocol-based digital data collaboration with videoconferencing is not yet well utilized in the imaging community. Videoconferencing, combined with proven low-cost solutions, can provide reliable functionality and speed, which will improve rapid, time-saving, and cost-effective communications, within large multifacility institutions or globally with the unlimited reach of the Internet. The aim of this project was to demonstrate the implementation of a low-cost hardware and software setup that facilitates global data collaboration using WebEx and GoToMeeting Internet protocol-based videoconferencing software. Both products' features were tested and evaluated for feasibility across 2 different Internet networks, including a video quality and recording assessment. Cross compatibility with an Apple OS is also noted in the evaluations. Departmental experiences with WebEx pertaining to clinical trials are also described. Real time remote presentation of dynamic data was generally consistent across platforms. A reliable and inexpensive hardware and software setup for complete Internet-based data collaboration/videoconferencing can be achieved. PMID- 22082550 TI - Compressive sensing-based interior tomography: preliminary clinical application. AB - Compressive sensing (CS)-based interior tomography is a state-of-the-art method for accurate image reconstruction from only locally truncated projections. Here, we report our preliminary interior tomography results reconstructed from raw projections of a patient acquired on a GE Discovery CT750 HD scanner. This is the first clinical application of the CS-based interior reconstruction techniques, and the results show an excellent match with those reconstructed from global projections. PMID- 22082552 TI - Simulation and adult learning. PMID- 22082553 TI - Growth of a simulation lab: engaging the learner is key to success. PMID- 22082554 TI - Procedural simulation. PMID- 22082555 TI - Physiological stress responses of emergency medicine residents during an immersive medical simulation scenario. PMID- 22082556 TI - Use of mannequin-based simulators in anesthesiology. PMID- 22082557 TI - Critical care simulation. PMID- 22082558 TI - Simulation applications in emergency medical services. PMID- 22082559 TI - High-fidelity simulation-emergency medicine. PMID- 22082560 TI - Simulations in internal medicine. PMID- 22082561 TI - Characterisation of [11C]PR04.MZ in Papio anubis baboon: a selective high affinity radioligand for quantitative imaging of the dopamine transporter. AB - N-(4-fluorobut-2-yn-1-yl)-2beta-carbomethoxy-3beta-(4'-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [(11)C]PR04.MZ ([(11)C]-1) has been developed using GMP compliant equipment. An adult female Papio anubis baboon was studied using a test-retest protocol with [(11)C]-1 in order to assess test retest reliability, metabolism and CNS distribution profile of the tracer in non human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (f(P)), plasma input functions and metabolic degradation of the radiotracer [(11)C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (V(T)) and non-displaceable binding potentials (BP(ND)) for various brain regions and the blood were obtained from kinetic modelling. [(11)C]-1 shows promising results as a selective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man. PMID- 22082562 TI - Methylenebissantin: a rare methylene-bridged bisflavonoid from Dodonaea viscosa which inhibits Plasmodium falciparum enoyl-ACP reductase. AB - A new methylene-bridged bisflavonoid, methylenebissantin (1), and nine known compounds, including flavonoids (2-5), diterpenoids (6 and 7), and phenol derivatives (8-10) were isolated from the aerial parts of Dodonaea viscosa Jacq. The structure elucidation was based on spectroscopic data analyses. The isolated compounds were evaluated for the inhibition of Plasmodium falciparum enoyl-ACP reductase (PfENR). Methylenebissantin (1) exhibited a moderate inhibition (IC(50) 91.13 MUM) against PfENR. PMID- 22082563 TI - A key cytochrome P450 hydroxylase in pradimicin biosynthesis. AB - Pradimicins A-C (1-3) are a group of antifungal and antiviral polyketides from Actinomadura hibisca. The sugar moieties in pradimicins are required for their biological activities. Consequently, the 5-OH that is used for glycosylation plays a critical role in pradimicin biosynthesis. A cytochrome P450 monooxygenase gene, pdmJ, was amplified from the genomic DNA of A. hibisca and expressed in Escherichia coli BL21(DE3). PdmJ introduced a hydroxyl group to G-2A (4), a key pradimicin biosynthetic intermediate, at C-5 to form JX134 (5). A d-Ala containing pradimicin analog, JX137a (6) was tested as an alternative substrate, but no product was detected by LC-MS, indicating that PdmJ has strict substrate specificity. Kinetic studies revealed a typical substrate inhibition of PdmJ activity. The optimal substrate concentration for the highest velocity is 115MUM under the test conditions. Moreover, the conversion rate of 4 to 5 was reduced by the presence of 6, likely due to competitive inhibition. Coexpression of PdmJ and a glucose 1-dehydrogenase in E. coli BL21(DE3) provides an efficient method to produce the important intermediate 5 from 4. PMID- 22082564 TI - Ocular ischemia with hypotony after injection of hyaluronic acid gel. AB - The authors experienced a case with ocular ischemia with hypotony following injection of a dermal filler for augmentation rhinoplasty. Immediately after injection, the patient demonstrated a permanent visual loss with typical fundus features of central retinal artery occlusion. Multiple crusted ulcerative patches around the nose and left periorbit developed, and the left eye became severely inflamed, ophthalmoplegic, and hypotonic. Signs of anterior and posterior segment ischemia were observed including severe cornea edema, iris atrophy, and chorioretinal swelling. The retrograde arterial embolization of hyaluronic acid gel from vascular branches of nasal tip to central retinal artery and long posterior ciliary artery was highly suspicious. After 6 months of follow up, skin lesions and eyeball movement became normalized, but progressive exudative and tractional retinal detachment was causing phthisis bulbi. PMID- 22082565 TI - Increased IL-17-producing CD4(+) T cells in patients with esophageal cancer. AB - Increased interleukin-17 (IL-17)-producing Th (Th17) cells have been described in a variety of human carcinoma cases, however, the mechanism of Th17 cells' accumulation in a tumor microenvironment remains elusive. This study was designed to investigate whether Th17 cells were involved in the development of esophageal cancer. We found that the proportion of Th17 cells increased within the peripheral blood and tumor tissues of esophageal cancer patients. Furthermore, the proportion of circulating Th17 cells was higher in advanced esophageal cancer patients than that in early esophageal cancer patients. In addition, the Th17 cells differentiation-related cytokines (IL-23, IL-1beta, and IL-6) and accumulation-related chemokines (CCL22 and CCL20) were present in a tumor microenvironment. Therefore, the findings may partly explain the cause for the increased proportion of Th17 cells and indicate a potential prognostic marker of Th17 cells in esophageal cancer. PMID- 22082566 TI - Serum amyloid A protects murine macrophages from lethal toxin-mediated death. AB - Lethal toxin, a key virulence factor produced by Bacillus anthracis, induces cell death, in part by disrupting numerous signaling pathways, in mouse macrophages. However, exposure to sublethal doses of lethal toxin allows some cells to survive. Because these pro-survival signaling events occur within a few hours after exposure to sublethal doses, we hypothesized that acute phase proteins might influence macrophage survival. Our data show that serum amyloid A (SAA) is produced in response to lethal toxin treatment. Moreover, pre-treatment of macrophages with exogenous SAA protected macrophages from lethal toxin-mediated death. Exogenous SAA activated the p38 mitogen activated protein kinase (MAP) kinase pathway, while lethal toxin mutants incapable of p38 activation were incapable of causing cell death. Chemical inhibition of the p38 activation pathway abrogated the protective effects of SAA. These data show that SAA affords protection against lethal toxin in mouse macrophages and link this response to the p38 pathway. PMID- 22082567 TI - Human myeloid dendritic cells treated with supernatants of rotavirus infected Caco-2 cells induce a poor Th1 response. AB - We have previously shown that human myeloid dendritic cells treated with purified rotavirus induce an allogenic Th1 response. To determine if rotavirus in the context of an intestinal microenvironment modulates the function of dendritic cells, we treated these cells with supernatants from non-infected or infected Caco-2 cells and studied their capacity to promote Th1 or Th2 responses. Dendritic cells treated with supernatants from rotavirus-infected Caco-2 cells promoted a significantly lower Th1 response, in comparison with those treated with purified rotavirus. We wanted to establish if TGF-beta1, induced, or TSLP, not induced, during rotavirus infection, could mediate this effect. Neutralization of TGF-beta but not TSLP in the supernatant prior to treatment of dendritic cells increased their capacity to promote a Th1 response. The results suggest that the TGF-beta1 induced by rotavirus could be an immune evasion mechanism, and may partially explain the poor rotavirus-specific T cell response we have previously evidenced. PMID- 22082568 TI - Induced cytokine response of human PMBC-cultures: correlation of gene expression and secretion profiling and the effect of cryopreservation. AB - The immune system is regulated by the complex interaction of multiple cytokines, which are secreted signaling molecules affecting other cells. In this work, we studied the cytokine response to several well-known stimulants, such as OKT-3, Con A, PWM, and SEB. Healthy donor cells (PBMCs) were cultivated for up to 72 h and the mRNA levels and cytokine release of four key cytokines (IL-2, IL-4, IFN gamma, and TNF-alpha) were analyzed by RT-PCR and bead-based multiplex analyses. The generated cytokine profiles showed characteristic expression patterns and secretion kinetics for each cytokine and substance. PWM/SEB and OKT-3 led to a very fast and long-lasting immune response, whereas Con A induced the slowest cytokine production. Cytokine concentrations also differed greatly. The highest IFN-gamma concentration was 1000 times higher than the respective IL-4 concentration. Gene expression and cytokine concentration profiles were strongly correlated during the time course. The chronological response of the donors' cytokine profiles coincided, but showed individual characteristics regarding the strength of the cytokine release. The comparison of stimulation experiments using freshly isolated and cryopreserved PBMCs showed that, for the observation of an immunological response at early points in time, gene expression experiments are more reliable than the measurement of cytokines in the cell culture supernatant. However, the freezing of cells influences the response significantly. The measurement of secreted proteins is the superior method at later points in time. PMID- 22082569 TI - Comparative dental development in Hispanopithecus laietanus and Pan troglodytes. PMID- 22082570 TI - Intrathecal combination of ziconotide and morphine for refractory cancer pain: a rapidly acting and effective choice. AB - Ziconotide is a nonopioid intrathecal analgesic drug used to manage moderate to severe chronic pain. The aim of this work is to assess the safety and efficacy of intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral opioids. Patients with malignant pain refractory to high oral opioids doses with a mean visual analogue scale of pain intensity (VASPI) score of >= 70 mm were enrolled. An IT combination therapy was administered: Ziconotide was started at a dose of 2.4 MUg/day, followed by increases of 1.2 MUg/day at intervals of at least 7 days, and an initial IT daily dose of morphine was calculated based on its oral daily dose. Percentage change in VASPI scores from baseline was calculated at 2 days, at 7 days, and weekly until the first 28 days. The mean percentage change of VASPI score from baseline was used for efficacy assessment. Safety was monitored based on adverse events and routine laboratory values. Twenty patients were enrolled, with a mean daily VASPI score at rest of 90+/-7. All had a disseminated cancer with bone metastases involving the spine. The percentage changes in VASPI mean scores from baseline to 2 days, 7 days, and 28 days were 39+/-13% (95% confidence interval [CI]=13.61 64.49, P<.001), 51+/-12% (95% CI=27.56-74.56, P<.001), and 62+/-13% (95% CI=36.03 87.89%, P<.001), respectively. Four patients experienced mild adverse events related to the study drugs. In conclusion, an IT combination of low doses of ziconotide and morphine allows safe and rapid control of oral opioid-refractory malignant pain. PMID- 22082571 TI - Automated image interpretation computer-assisted diagnostics. PMID- 22082572 TI - Where have all the pioneers gone? PMID- 22082573 TI - Following the cutting edge.... PMID- 22082574 TI - First clinical evaluation of a luminal self-expanding shield in patients with intermediate coronary lesions. AB - AIMS: Earlier generation self-expanding stents (SExS) showed high restenosis rates and long-term stent over-expansion. A novel SExS with reduced outward expansive force has been developed to overcome these limitations. This first-in human study aimed to evaluate the safety and feasibility of the low pressure self expanding nitinol-based vProtectTM luminal shield (LS) in the treatment of intermediate coronary lesions. METHODS AND RESULTS: A total of 29 patients with clinical evidence of myocardial ischaemia and intermediate de novo coronary lesions were included. The LS was deployed after low-pressure balloon pre dilatation. Acute procedural and device success was achieved in all patients. Angiographic follow-up at nine months showed an in-stent lumen loss of 0.50+/ 0.30 mm and a binary restenosis rate of 10.3%. There were no cases of late LS over-expansion or acute/late malapposition as evaluated by intravascular ultrasound (IVUS). The cumulative major adverse cardiac events (MACE) rate at nine months was 10.3%, consisting of three target lesion revascularisations, with no cases of death, myocardial infarction or stent thrombosis. CONCLUSIONS: Implantation of the LS in non-complex coronary lesions of intermediate severity was feasible, safe, and resulted in low rates of late loss and restenosis. IVUS analysis at nine months showed favourable mechanical properties of the LS without evidence of late device over-expansion. PMID- 22082575 TI - Comparison of target-lesion revascularisation between left main coronary artery bifurcations and left anterior descending coronary artery bifurcations using the one and two stent approach with sirolimus-eluting stents. AB - AIMS: Lesion location might influence the efficacy of the bifurcation two-stent approach relative to the one-stent approach. METHODS AND RESULTS: One-year outcomes after sirolimus-eluting stent (SES) implantation with the two-stent approach were compared to those with the one-stent approach in left main coronary artery (LMCA) bifurcation (945 lesions) and in left anterior descending coronary artery (LAD) bifurcation (1271 lesions). The two-stent approach was used more frequently in LMCA than in LAD. The target-lesion revascularisation (TLR) rate in the two-stent group was significantly higher than that in the one-stent group in LMCA (24.2% vs. 5.6%, p<0.0001), but not in LAD (9.0% vs. 5.4%, p=0.056). Adjusted odds ratio of two-stent versus one-stent for TLR was 4.93 (3.01-8.08, p<0.0001) in LMCA and 1.15 (0.64-2.07, p=0.63) in LAD, respectively (interaction p<0.0001). Angiographic restenosis rates in the main branch were significantly higher in the two-stent group in both LMCA and LAD (11.0% vs. 4.9%, p=0.02; and 13.2% vs. 6.8%, p=0.02). Restenosis rates in the side branch were significantly higher in the two-stent group in LMCA (35.3% vs. 14.5%, p<0.0001), but not in LAD (15.1% vs. 22.6%, p=0.07). CONCLUSIONS: Risk of TLR after bifurcation stenting in lesions that needed the two-stent approach was significantly different between LMCA and LAD bifurcations. PMID- 22082576 TI - Transendocardial autologous bone marrow in myocardial infarction induced heart failure, two-year follow-up in an open-label phase I safety study (the TABMMI study). AB - AIMS: To assess the hypothesis that fluoroscopically-guided helical needle transendocardial delivery of autologous bone marrow (ABM) mononuclear cells (MNCs) in chronic post myocardial infarction patients is safe and improves ejection fraction (EF). METHODS AND RESULTS: Twenty ischaemic heart failure patients with an EF <=40% were enrolled. ABMMNCs were prepared, counted for CD34+ and CD133+ content, and delivered percutaneously to the heart at 5 to 10 peri infarct sites. Two-dimensional (2D) transthoracic echocardiography, EF measurements, Holter, and exercise tolerance time (ETT) were performed at baseline, one week (wk), and 6, 12, and 24 months (mo). 96+/-29 million ABMMNCs were injected into 8.5+/-2.6 peri-infarct sites over 42+/-17 minutes (n=20). There were no adverse events associated with the catheter-based cell transplantation procedure or significant increases in ventricular events on Holter. EF improved over baseline from 34.9+/-4.3% to 41.9+/-5.1% at 12 mo to 42.2+/-7.1% (p=0.00005) at 24 mo. ETT improvements were statistically significant from 246+/-113 sec to 373+/-183 sec at 12 mo and 371+/-181 sec at 24 mo (p=0.006). CONCLUSIONS: ABMMNCs delivered with the helical needle transendocardial catheter was safe in this uncontrolled open label study. Increased EF and ETT support the safety of the procedure and technologies involved and warrant additional investigation. PMID- 22082577 TI - Evaluating the safety of very short-term (10 days) dual antiplatelet therapy after GenousTM bio-engineered R stentTM implantation: the multicentre pilot Genous trial. AB - AIMS: Percutaneous coronary stenting is synonymous with dual antiplatelet therapy, ranging from four weeks to lifelong. However, even short-term (four weeks) therapy with aspirin and thienopyridines is occasionally contraindicated. No study has ever appraised very short-term dual antiplatelet therapy after stenting. We thus aimed to exploit the pro-healing features of the GenousTM Bio engineered R stentTM (Genous) (OrbusNeich Medical Technologies, Hong Kong, People's Republic of China) and evaluate the safety of a 10-day dual antiplatelet regimen after its implantation in up to 50 patients. METHODS AND RESULTS: Forty nine consecutive patients with de novo lesions located in vessels able to receive a 2.5 mm Genous stent were included. After stenting, they received lifelong aspirin plus clopidogrel for 10 days. The primary endpoint of the study was sudden cardiac death, myocardial infarction or angiographic evidence of stent thrombosis ascribable to the study stent. Almost 70% of patients effectively discontinued clopidogrel nine to 11 days after stenting. At three-month clinical follow-up, no patient had died or reached the primary endpoint (95%; confidence interval 0-7.3%). Repeat revascularisation occurred instead in three (6.1%[2.1 16.5%]), with target lesion revascularisation in two (4.1%[1.1-13.7%]). CONCLUSIONS: Even very short-term dual antiplatelet therapy seems safe after coronary stenting with Genous in de novo coronary artery lesions located in secondary branch vessels. This preliminary exploratory study gives some support to planning a large trial to test the hypothesis of short dual antiplatelet therapy following Genous stent implantation. PMID- 22082578 TI - Optical coherence tomography for guidance of treatment of in-stent restenosis with cutting balloons. AB - AIMS: The treatment of in-stent restenosis (ISR) remains a challenge with poor immediate results and higher restenosis rate than in de novo lesions. We propose, based on a consecutive series of patients treated with cutting balloon, a strategy of aggressive device selection based on the results of serial FD-OCT assessment. METHODS AND RESULTS: Fourteen consecutive ISR lesions were evaluated both angiographically and with frequency domain optical coherence tomography (FD OCT) (C7; LightLab Imaging Inc., Westford, MA, USA). Cutting balloon (CB) was used in all cases, sized firstly according to conventional angiographic criteria and then upgraded based on OCT assessment with the aim of creating cuts as close as possible to the struts. OCT data analysis included measurements of lumen and stent area, minimal distance lumen-struts and residual plaque neointimal hyperplasia. With an OCT guided CB strategy, the final minimal lumen cross sectional area (MLCSA) after the final treatment reached 6.68+/-1.14 mm2, with a reduction from 69% to 25% of neointimal hyperplasia. In the patients with a two step strategy using a first CB guided by angiography and a second CB guided by OCT, the increase in CB diameter was 0.5 mm, achieving an increase in MLCSA area from 4.9+/-0.42 to 6.35+/-0.92 mm2 with a reduction from 41% to 27% of neointimal hyperplasia. CONCLUSIONS: The OCT measurements of strut-to-strut distance allow safe upsizing of the CB with an acceptable lumen increase before deployment of a new DES. The strategy appears of particular usefulness for a DEB strategy with no intention to implant new stents. PMID- 22082579 TI - In vitro and in vivo characterisation of biodegradable polymer-based drug-eluting stent. AB - AIMS: The objective of this study was to investigate the structural integrity and early vascular response of a polylactic acid-coated (i.e., biodegradable polymer) coronary drug-eluting stent (DES) (BioMatrixTM; Biosensors International, Singapore) to three currently marketed FDA/CE- mark approved non-erodible polymer coated DES in a porcine model. METHODS AND RESULTS: BioMatrixTM, XIENCE VTM (Abbott Vascular, Santa Clara, CA, USA), TAXUS(r) LiberteTM (Boston Scientific, Natick, MA, USA), and Cypher SELECTTM (Cordis, Johnson & Johnson, Miami, FL, USA) stents were implanted in pig coronaries for seven days. Polymer integrity was assessed by scanning electron microscopy (SEM) following tissue digestion. In vitro expansion of the BioMatrixTM was also performed. SEM analysis of in vivo stents demonstrated polymer defects on the abluminal surface of all DES including polymer cracking (BioMatrixTM), bridging (TAXUS LiberteTM), round-small defects (Cypher SELECTTM), and flaking (XIENCE VTM). Histologically, the myocardium revealed no evidence of acute myocardial infarction or microscopic scarring, moreover all intramyocardial vessels were found to be patent with no evidence of emboli. In vitro results demonstrated greater BioMatrixTM polymer cracking and lifting. CONCLUSIONS: These results illustrate the presence of polymer defects in all DES (TAXUS LiberteTM, Cypher SELECTTM, XIENCE VTM, BioMatrixTM) implanted seven-days in pigs, with absence of myocardial damage in this small number of samples. Polymer coating irregularity was greater in BioMatrixTM stent expanded in vitro as compared to in vivo, suggesting simulated benchtop deployment induces greater damage to the biodegradable polymer coating than in vivo deployment in healthy porcine coronary arteries. PMID- 22082580 TI - Percutaneous renal artery intervention versus medical therapy in patients with renal artery stenosis: a meta-analysis. AB - AIMS: Patients with renal artery stenosis are treated with percutaneous intervention, but randomised studies are inconclusive. We aimed to compare renal percutaneous revascularisation versus medical therapy. METHODS AND RESULTS: A systematic search for randomised controlled studies yielded three studies comparing renal angioplasty and two studies comparing renal angioplasty with stenting versus medical therapy, respectively. Six sets of data were extracted focusing on systolic and diastolic blood pressure as well as serum creatinine at follow-up. The five trials included 1,030 patients with renal artery stenosis. There was a trend toward, but no significant improvement in, systolic blood pressure (weighted mean difference [WMD] -2.76 mmHg, 95% confidence interval (CI) -5.71 to 0.18; p=0.07), diastolic blood pressure, (WMD -1.18 mmHg, 95% CI -2.69 to 0.32; p=0.12), or serum creatinine (WMD -7.26 mmol/L, 95% CI -14.99 to 0.47; p=0.07) in the patients who underwent percutaneous intervention compared to the medical therapy group. All but one trial showed at least a moderate overall bias risk. CONCLUSIONS: We did not find a significant improvement in blood pressure or renal function in patients with renal artery stenosis treated with renal artery revascularisation compared to medical therapy alone. However, trial quality was a limitation. PMID- 22082581 TI - Current insights in endovascular repair of ruptured abdominal aortic aneurysms. AB - In patients presenting with a ruptured abdominal aortic aneurysms (AAA), a choice can be made whether or not to offer treatment (selective treatment policy). Patients with a realistic expectation of survival after surgery, identified by several available prediction models, can be offered two treatment options: conventional "open" surgical repair and endovascular "minimally invasive" repair. Conventional open repair carries a significant morbidity and mortality, due to the combined effects of general anaesthesia and surgical exposure. Based on anatomical criteria assessed on a pre-operative CT angiography scan, approximately half of the ruptured AAA are suitable for endovascular aneurysm repair (EVAR). The majority of comparative studies show a clear trend towards lower perioperative mortality for endovascular repair compared to open surgery. The overall analyses of EVAR compared to open surgery, taking one randomised controlled trial and 23 available observational studies into account, showed a 38% decrease in 30-day or hospital mortality rate (Peto odds ratio 0.62; 95% CI 0.52 to 0.74). However, these mainly observational studies show considerable heterogeneity. Furthermore, potential selection bias, selecting patients for endovascular repair constituting a haemodynamically lower-risk category with a more favourable EVAR suitable anatomic configuration, makes a proper comparison unlikely. Therefore, randomised controlled trials, although difficult to perform in an acute severe condition like ruptured AAA, are needed to identify possible benefits of EVAR over open surgery in patients with a ruptured AAA. PMID- 22082582 TI - Cardiovascular risk profile of patients included in stent trials; a pooled analysis of individual patient data from randomised clinical trials: insights from 33 prospective stent trials in Europe. AB - AIMS: Few data document trends in cardiovascular (CV) risk-factors in patients with or without previous symptomatic CV disease. We assessed the prevalence and trends in (non) modifiable CV risk-factors, and the use of cardioprotective therapies in patients enrolled in coronary stent trials. METHODS AND RESULTS: This analysis included prospective data on 10,253 mainly European adults who were enrolled in 32 coronary stent studies between 1995 and 2006. Data was collected at the time of enrolment using a standardised patient clinical record form, and was analysed by considering three consecutive time periods: 1995-1997 (I), 1998 2002 (II) and 2003-2006 (III) rendering approximately equal numbers per period. Overall the proportion of active smokers remained constant (Period I to III: 28%, 27%, 21%, p=0.45), however the proportion increased in females below 50 years (about 2%/ year, R.RR: 1.20, P: 0.05 period III versus I). Prevalent diabetes increased (16%, 17%, 25%; p=0.029). The prevalence of a body-mass index (BMI) >=25 kg/m2 was high, but no trend was observed (69%, 68%, 70%; p=0.24). The proportion of patients with elevated blood pressure (i.e., >=140/90 mmHg, in diabetes >=130/80 mmHg) remained unchanged (55%, 50.%, 53%; p=0.22), despite an increase in the number of patients taking anti-hypertensive agents (84%, 89%, 90%; p=0.30). Conversely, the proportion of patients with elevated total cholesterol (i.e., >=4.5 mmol/L) decreased (80%, 66%, 52%; p=0.002), which was consistent with the increase in patients taking lipid lowering drugs (32%, 62%, 69%; p=0.083). The portion of patients reaching therapeutic targets for blood lipids improved, but no improvement was seen in blood pressure control (p=0.29). CONCLUSIONS: There is an unmet clinical need in primary and secondary CV prevention in Europe. Patients requiring PCI are an important target population in whom lifestyle changes and aggressive secondary preventative measures should be aimed. Ultimately PCI should open the door towards optimising secondary prevention. PMID- 22082583 TI - Tools & techniques: Percutaneous intervention of saphenous vein graft lesions. PMID- 22082584 TI - How should I treat pulmonary arteriovenous malformations in a patient with Rendu Osler disease presenting with transient ischaemic attack. AB - BACKGROUND: A 42-year-old man with no cardiovascular risk factors or history was admitted for evaluation of an episode of transient ischaemic attack (TIA). He had no cardiovascular risk factors and his physical examination was unremarkable. INVESTIGATION: Physical examination, electrography, transesophageal echocardiogram, coronary angiogram. DIAGNOSIS: Intrapulmonary shunting, in the presence of arteriovenous malformations, possible hereditary haemorrhagic telangectasia. TREATMENT: Transcatheter occlusion of multiple pulmonary arteriovenous malformations using an AMPLATZER vascular plug. PMID- 22082585 TI - Argan oil improves surrogate markers of CVD in humans. AB - Limited - though increasing - evidence suggests that argan oil might be endowed with potential healthful properties, mostly in the areas of CVD and prostate cancer. We sought to comprehensively determine the effects of argan oil supplementation on the plasma lipid profile and antioxidant status of a group of healthy Algerian subjects, compared with matched controls. A total of twenty healthy subjects consumed 15 g/d of argan oil - with toasted bread - for breakfast, during 4 weeks (intervention group), whereas twenty matched controls followed their habitual diet, but did not consume argan oil. The study lasted 30 d. At the end of the study, argan oil-supplemented subjects exhibited higher plasma vitamin E concentrations, lower total and LDL-cholesterol, lower TAG and improved plasma and cellular antioxidant profile, when compared with controls. In conclusion, we showed that Algerian argan oil is able to positively modulate some surrogate markers of CVD, through mechanisms which warrant further investigation. PMID- 22082586 TI - beta-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells. AB - BACKGROUND: Cyclooxygenase-2 (COX-2) overexpression in colorectal cancer increases levels of its pro-tumorigenic product prostaglandin E2 (PGE(2)). The recently identified colorectal tumour suppressor 15-prostaglandin dehydrogenase (15-PGDH) catalyses prostaglandin turnover and is downregulated at a very early stage in colorectal tumorigenesis; however, the mechanism responsible remains unclear. As Wnt/beta-catenin signalling is also deregulated early in colorectal neoplasia, a study was undertaken to determine whether beta-catenin represses 15 PGDH expression. METHODS: The effect of modulating Wnt/beta-catenin signalling (using beta-catenin siRNA, mutant TCF4, Wnt3A or GSK3 inhibition) on 15-PGDH mRNA, protein expression and promoter activity was determined in colorectal cell lines by immunoblotting, qRT-PCR and reporter assays. The effect of beta-catenin deletion in vivo was addressed by 15-PGDH immunostaining of beta-catenin(-/lox) villin-creERT2 mouse tissue. 15-PGDH promoter occupancy was determined using chromatin immunoprecipitation and PGE(2) levels by ELISA. RESULTS: The study shows for the first time that beta-catenin knockdown upregulates 15-PGDH in colorectal adenoma and carcinoma cells without affecting COX-2 protein levels. A dominant negative mutant form of TCF4 (dnTCF4), unable to bind beta-catenin, also upregulated 15-PGDH; conversely, increasing beta-catenin activity using Wnt3A or GSK3 inhibition downregulated 15-PGDH. Importantly, inducible beta-catenin deletion in vivo also upregulated intestinal epithelial 15-PGDH. 15-PGDH regulation occurred at the protein, mRNA and promoter activity levels and chromatin immunoprecipitation indicated beta-catenin/TCF4 binding to the 15-PGDH promoter. beta-catenin knockdown decreased PGE(2) levels, and this was significantly rescued by 15-PGDH siRNA. CONCLUSION: These data suggest a novel role for beta-catenin in promoting colorectal tumorigenesis through very early 15 PGDH suppression leading to increased PGE(2) levels, possibly even before COX-2 upregulation. PMID- 22082587 TI - Clinical application of a systems model of apoptosis execution for the prediction of colorectal cancer therapy responses and personalisation of therapy. AB - OBJECTIVE: Key to the clinical management of colorectal cancer is identifying tools which aid in assessing patient prognosis and determining more effective and personalised treatment strategies. We evaluated whether an experimental systems biology strategy which analyses the susceptibility of cancer cells to undergo caspase activation can be exploited to predict patient responses to 5 fluorouracil-based chemotherapy and to case-specifically identify potential alternative targeted treatments to reactivate apoptosis. DESIGN: We quantified five essential apoptosis-regulating proteins (Pro-Caspases 3 and 9, APAF-1, SMAC and XIAP) in samples of Stage II (n = 13) and III (n=17) tumour and normal colonic (n = 8) tissue using absolute quantitative immunoblotting and employed systems simulations of apoptosis signalling to predict the susceptibility of tumour cells to execute apoptosis. Additional systems analyses assessed the efficacy of novel apoptosis-inducing therapeutics such as XIAP antagonists, proteasome inhibitors and Pro-Caspase-3-activating compounds in restoring apoptosis execution in apoptosis-incompetent tumours. RESULTS: Comparisons of caspase activity profiles demonstrated that the likelihood of colorectal tumours to undergo apoptosis decreases with advancing disease stage. Systems-level analysis correctly predicted positive or negative outcome in 85% (p=0.004) of colorectal cancer patients receiving 5-fluorouracil based chemotherapy and significantly outperformed common uni- and multi-variate statistical approaches. Modelling of individual patient responses to novel apoptosis-inducing therapeutics revealed markedly different inter-individual responses. CONCLUSIONS: Our study represents the first proof-of-concept example demonstrating the significant clinical potential of systems biology-based approaches for predicting patient outcome and responsiveness to novel targeted treatment paradigms. PMID- 22082588 TI - Three cases of myasthenia gravis from one family with variations in clinical features and serum antibodies. AB - Myasthenia gravis, an autoimmune disorder affecting neuromuscular transmission, is mainly sporadic while familial cases are very rare. Usually familial myasthenia gravis cases have uniform clinical symptoms as well as serum anti acetylcholine receptor antibodies. Interestingly, in our cases varying clinical types of myasthenia gravis and seropositive/seronegative anti-acetylcholine receptor antibodies coexisted in the same family. The mother and her daughter both had ocular myasthenia gravis, detectable anti-acetylcholine receptor antibodies and non-detectable anti-muscle-specific kinase antibodies, and good responses to medications. The son displayed ocular symptoms at the onset, and then progressed into a generalized form after 1 year. His serum anti acetylcholine receptor antibodies and anti-muscle-specific kinase antibodies were both negative. Neither corticosteroids nor thymectomy alleviated his symptoms. Human leukocyte antigen DQA1*0301 allele sharing by the three patients may be involved in their genetic susceptibility to myasthenia gravis, and subtle differences in human leukocyte antigen DQB1 alleles may be associated with their variations in clinical features and serum antibodies. PMID- 22082589 TI - Neurotrophic corneal ulcer after retrobulbar injection of chlorpromazine. AB - An 80-year-old woman with a painful, poorly seeing right eye underwent retrobulbar chlorpromazine injection for pain control. After the injection, the patient's symptoms improved; however, a neurotrophic ulcer developed within 2 weeks after the procedure. It is postulated that chlorpromazine may lead to sensory denervation to the cornea with the subsequent development of neurotrophic keratopathy, as observed in this case. Awareness of this potential adverse effect is important for proper patient safety, education, and postinjection management. PMID- 22082590 TI - Non-traumatic subperiosteal orbital hematoma as a presenting sign of chronic myelogenous leukemia. AB - We present a case with a nontraumatic subperiosteal orbital hematoma as a presenting sign of chronic myelogenous leukemia. A previously healthy 34 year-old man presented with a 2-day history of right upper eyelid swelling. CT scan revealed a subperiosteal mass, and routine blood tests revealed a white blood cell count of 290,000/MUl with normal platelet count. Chronic myelogenous leukemia was diagnosed based on a subsequent bone marrow biopsy. After orbitotomy and evacuation of the hematoma, the patient's visual acuity and motility returned to normal. In conclusion, chronic myelogenous leukemia should be considered in the differential diagnosis of nontraumatic subperiosteal orbital hematoma. PMID- 22082591 TI - A unique case of foreign-body associated orbital myositis. AB - A 50-year-old woman presented with a 2-week history of diplopia and right-sided orbital pain with eye movement. Examination revealed an edematous, ptotic right upper eyelid with conjunctival hyperemia, proptosis, and significant limitation to upward and downward ductions on the right. MRI was significant for a homogeneously enhancing lesion within the superior rectus muscle. A laboratory evaluation seeking an infectious, inflammatory, or autoimmune process was nonrevealing. A diagnosis of orbital myositis was made, and the patient experienced significant improvement with oral corticosteroids. The patient's symptoms, however, recurred after attempts at a slow taper of the corticosteroids. An orbital biopsy of the lesion revealed fibroadipose tissue containing irregularly shaped yellow-white deposits birefringent under polarized light, suggestive of silica crystals. The patient denied any history of trauma or prior surgery. An intraorbital triamcinolone injection to the superior orbit allowed resolution of symptoms and a successful taper off systemic corticosteroids. PMID- 22082592 TI - Idiopathic inflammation of the orbit and contiguous structures. AB - Idiopathic orbital inflammation is a common cause of acute orbital signs and symptoms. It is typically confined to the bony orbit; however, it can rarely involve contiguous structures with or without lytic change raising clinical suspicion for malignancy. Three cases of idiopathic inflammation of the orbit that affected adjacent structures are reported here; 2 cases had maxillary sinus involvement, while a third had extension in the temporal fossa. PMID- 22082593 TI - Congenital dacryocystocele: comparative findings of dacryoendoscopy and histopathology in a patient. AB - A full-term baby girl showed a bluish mass at birth in the right medial canthal area. She later demonstrated dacryocystitis and cellulitis. Although probing was performed, it was unsuccessful, and the dacryocystitis and cellulitis worsened. Computed tomography showed a dilated lacrimal sac, an enlarged nasolacrimal canal and a nasal cyst. Topical and intravenous systemic antibiotics were then started, and the symptoms partially subsided. Surgery was performed under general anesthesia with endoscopic assistance, under which cystic distention was visualized beneath the inferior turbinate. A dacryoendoscope showed injection and hemorrhages on the inner wall of the cyst. Marsupialization of the cyst was performed. Histopathologic examination showed submucosal tissue including fibrous thickening with infiltration of mononuclear leukocytes. The patient remained symptom free 6 months thereafter. Dacryoendoscopy for a congenital dacryocystocele demonstrated injection with hemorrhages, and this inflammatory sign corresponded to the histopathologic findings. PMID- 22082594 TI - Isolated squamous cell carcinoma of the orbital apex. AB - A 43-year-old woman (Case 1), 63-year-old man (Case 2), and a 67-year-old man (Case 3) presented with diplopia (Cases 1, 2, and 3) and upper-eyelid ptosis (Cases 1 and 3). The cases had preceding cranial nerve V1 disturbances ranging from 3 months to 8 years. Each demonstrated complete internal ophthalmoplegia and external ophthalmoplegia. No case had a cutaneous squamous cell carcinoma (SCC) on presentation or by history. Imaging revealed isolated orbital apex masses. Tumor biopsies revealed SCCs of various differentiations. Systemic workup revealed no extraorbital malignancy. All received radiation therapy, and 2 patients underwent adjuvant chemotherapy. One patient is alive since diagnosis (49 months). In Case 2, SCC developed in the contralateral orbit, and the patient died 19 months after diagnosis; and Case 3 died 12 months after diagnosis. These isolated cases of orbital SCC may have arisen from orbital choristomatous squamous epithelium, may represent de novo or metastatic tumors, or may be manifestations of occult perineural spread. PMID- 22082595 TI - Histopathology of brow fat in thyroid-associated orbitopathy. AB - PURPOSE: We propose that brow enlargement seen in patients with thyroid associated orbitopathy (TAO) occurs secondary to the autoimmune process in Graves disease and that the changes in brow fat are histologically identical to those seen in orbital fat. METHODS: With informed consent, brow and orbital fat was obtained from patients with TAO and from patients with no significant past medical history undergoing orbital decompression, blepharoplasty, and/or brow fat removal. Histologic examination was performed on the orbital and brow fat. RESULTS: Fat histologies obtained from patients with TAO and those without known systemic disease were compared. Specimens from patients with TAO showed an increase of fibrosis and fibrous septae. Furthermore, certain biologic markers, including insulin-like growth factor 1 receptor beta (IGF-1Rbeta) and thyroid stimulating hormone receptor (TSHR), were increased in the fat obtained from patients with TAO. This was identical in both the brow and the orbital fat. Fat from patients with no significant past medical history showed normal fat histology, absence of fibrous septae, and decreased marker expression. CONCLUSION: Graves disease is a systemic autoimmune disease that affects patients in a variety of ways. In addition to the orbital changes seen in these patients, we have observed an increase in the brow fat compartment. We are intrigued to find that the histologic changes are identical in both the orbital and the brow fat of patients with TAO. The increased IGF-1Rbeta and TSHR expression in both the brow and the orbital fat further support their role as putative markers in patients with Graves disease. PMID- 22082596 TI - A unique association of granuloma of the lower eyelid to prior trauma. AB - A 5-year-old girl presented with a mass of the lower eyelid causing lower eyelid retraction and traction in upgaze. The patient had a recent history of minor trauma to the area. An orbitotomy was performed with lateral canthotomy and cantholysis to allow for dissection of the lesion, which was found in the anterior lamella of the lower eyelid. Pathologic review showed non-necrotizing granulomatous inflammation with granulation tissue. Reports of granulomas of the oral mucosa secondary to trauma are common in the dental literature. This is a unique case in that it is the first report of a subcutaneous granuloma of the eyelid arising secondary to trauma. PMID- 22082597 TI - Eyelid lacerations secondary to caesarean section delivery. AB - A 32-week-gestation female was delivered emergently via caesarian section to a mother in premature labor due to placental abruption. On delivery, the neonate was noted to have sustained right upper and lower eyelid full-thickness lacerations extending from the medial canthal area with associated right upper and lower full-thickness canalicular lacerations. The neonate underwent same-day surgical repair of her eyelid lacerations with stenting of her canalicular system with a Crawford tube. At 2 months postoperatively, the child is opening her right upper eyelid without any signs of deprivation ambylopia. This case demonstrates the need to inform expectant mothers of the intrinsic risks of periorbital trauma during the birthing process that may result in visual loss through either ambylopia and/or globe injury. PMID- 22082599 TI - Acute recurrence of orbital cavernous hemangioma in a young man: a case report. AB - A 29-year-old man presented with a history of prominent left eye of 6 months' duration. He also reported fluctuating blurred vision since 15 days ago. On examination, proptosis of 3 mm was noted in the left eye. Computed tomography (CT scan) of the orbits showed a well-circumscribed, hyperdense, intraconal mass lesion in left orbit, located in the inferotemporal quadrant. Orbitotomy was performed, and the tumor was delivered with an intact capsule. The clinical diagnosis of cavernous hemangioma was confirmed on histopathologic examination. The presence of intact capsule was confirmed grossly and with histopathology. The patient returned 6 weeks after surgery with recurrent proptosis. Repeated CT scan showed a recurrent intraconal mass of similar characteristics as in the primary presentation. A repeated orbitotomy was done, and the tumor was removed intact. Histopathology of the recurrent tumor confirmed the diagnosis of cavernous hemangioma. We report a rare case of orbital cavernous hemangioma with short-term recurrence (6 weeks). PMID- 22082598 TI - Blepharospasm in a patient with pontine capillary telangiectasia. AB - Blepharospasm is rarely due to an identifiable etiology. In the majority of cases, imaging fails to reveal any structural lesion. Here we describe an otherwise healthy patient with blepharospasm who was found to have pontine capillary telangiectasia. We propose a potential association between blepharospasm and pontine capillary telangiectasia. PMID- 22082600 TI - External dacryocystorhinostomy outcomes in sarcoidosis patients. AB - PURPOSE: To determine surgical outcomes after external dacryocystorhinostomy (DCR) surgery in patients with sarcoidosis. METHODS: We retrospectively reviewed the charts of all patients with sarcoidosis who underwent external DCR surgery between January 2001 and January 2010. Clinical data reviewed included patient demographics, immunosuppressive therapies, biopsy results, use of intraoperative triamcinolone, and postoperative outcomes and complications. Success was defined as resolution of epiphora. RESULTS: External DCR was performed on 13 sides of 9 patients with sarcoidosis. Four patients were systemically immunosuppressed with methotrexate or plaquenil, and 4 patients used inhaled corticosteroids only. Intraoperative biopsy in 10 cases (9 patients) revealed non-necrotizing granulomatous inflammation (8 cases) and chronic inflammation (2 cases). Silicone stents were removed at a mean of 2.9 months. Initial DCR surgery was successful in 10 of 13 (87%) surgeries with an average follow up of 31 months (range, 14 to 48 months). None of the 5 surgeries (4 patients) with intralesional triamcinolone injections failed, compared with 3 of 8 (38%) surgeries without intralesional triamcinolone. Of the 3 failures, 2 early failures (3 months) were successfully treated with balloon catheter dilation. In the one patient with a late failure (47 months), subsequent balloon catheter dilation failed. All 3 patients who experienced failures used inhaled corticosteroids only. In contrast, 4 of the 6 patients with successful surgery were systemically immunosuppressed. Complications such as punctal erosion, wound necrosis, or cerebrospinal fluid leak did not occur. CONCLUSIONS: External DCR surgery successfully treats nasolacrimal duct obstruction associated with sarcoidosis. Intralesional triamcinolone may improve the success rate without added complications. Long-term success may be less in patients not receiving systemic immunosuppressive therapy. PMID- 22082601 TI - Head and neck large cell neuroendocrine carcinoma should be separated from atypical carcinoid on the basis of different clinical features, overall survival, and pathogenesis. AB - According to the 2005 World Health Organization classification of head and neck tumors, neuroendocrine tumors can be subdivided into typical carcinoid, atypical carcinoid, and small cell carcinoma. Similar tumors diagnosed as large cell neuroendocrine carcinomas (LCNECs) in the lung are diagnosed as atypical carcinoids in the head and neck region. We studied neuroendocrine tumors and analyzed whether LCNEC should be separated from atypical carcinoid in the head and neck region. Twenty-three cases of primary head and neck neuroendocrine tumors were included and subdivided into typical carcinoid, atypical carcinoid, and small cell carcinoma according to the 2005 World Health Organization guidelines, and then LCNECs were separated from atypical carcinoids according to modified criteria using the Ki-67-labeling index and mitotic count. Clinical information and survival data were obtained, and immunohistochemical studies for p53 were conducted. The 5-year survival rates for the 2 typical carcinoids, 7 atypical carcinoids, 7 LCNECs, and 7 small cell carcinomas were 100.0%, 83.3%, 21.4%, and 20.8%, respectively (P=0.032). The LCNEC patients were older (mean age, 61 vs. 41 y; P=0.038), more commonly in advanced stage (stages III and IV 100% vs. 28.6%, P=0.01), with a poorer prognosis (5-year survival 21.4% vs. 83.3%, P=0.03), and more commonly had tumors overexpressing p53 (85.7% vs. 0%, P=0.005) as compared with atypical carcinoid patients. LCNECs should be separated from atypical carcinoids as a new entity of neuroendocrine carcinoma in the head and neck region. The new classification may provide better risk stratification and useful information for proper treatment. PMID- 22082602 TI - Composite intestinal adenoma-microcarcinoid. AB - Composite intestinal adenoma and microcarcinoid is a rare intestinal neoplasm consisting of intermingled adenomatous and well-differentiated neuroendocrine components. A few case reports and small series have suggested an indolent clinical course for this entity. We reported 7 cases of composite intestinal adenoma-microcarcinoid, including their morphologic features and clinical follow up, both in biopsy and resection specimens. We identified 7 cases of composite intestinal adenoma-microcarcinoid from our pathology database. Five were from the large intestine, and 2 were in the duodenum. Morphologically, all microcarcinoids exhibited low-grade cytologic atypia and were devoid of significant pleomorphism, necrosis, and mitotic activity. Among the 7 lesions, 6 had a lobular architecture with smooth borders and mucosa-confined microcarcinoids; none had neuroendocrine carcinoma in subsequent resections. However, 1 colonic case had carcinoid cells penetrating the muscularis mucosae into the submucosa with an infiltrative border, and the resection showed metastatic high-grade neuroendocrine carcinoma in 1 lymph node. Composite intestinal adenoma-microcarcinoid is extremely rare. Although composite mucosa-confined adenoma-microcarcinoid is likely to have an indolent behavior, submucosal invasion by the neuroendocrine component may be associated with aggressive behavior. PMID- 22082603 TI - Low-grade ovarian serous neoplasms (low-grade serous carcinoma and serous borderline tumor) associated with high-grade serous carcinoma or undifferentiated carcinoma: report of a series of cases of an unusual phenomenon. AB - Recent literature has suggested a dual pathway of ovarian serous carcinogenesis, with most serous carcinomas falling into 1 of 2 categories, low grade and high grade. These are considered to represent 2 distinct tumor types with a different underlying pathogenesis and associated with different molecular events, clinical behavior, and prognosis. Low-grade serous carcinoma is thought to evolve in many instances from a preexisting serous borderline tumor and cystadenoma. Given the distinct pathogenesis and different molecular events, it is expected that the coexistence of low-grade and high-grade serous carcinoma would be rare or may even be mutually exclusive; moreover, there are very few reported examples in the literature. We report a series of 7 cases in patients aged 34 to 78 years in whom ovarian low-grade serous carcinoma (4 cases, including 3 with associated serous borderline tumor), serous borderline tumor (2 cases), or seromucinous borderline tumor (1 case) was associated with a high-grade carcinoma, either high-grade serous (5 cases) or undifferentiated carcinoma (2 cases). The low-grade and high grade components coexisted in the original neoplasm in 4 cases, and the high grade component was present only in recurrence in 3 cases. In both instances, the undifferentiated carcinoma had a focal rhabdoid morphology, and alternative primary sites of tumor were excluded by a combination of clinical, radiologic, and pathologic parameters. We illustrate that low-grade serous carcinoma or serous borderline tumor ("low-grade" serous neoplasms) may rarely be associated with, and probably give rise to, a high-grade carcinoma, either high-grade serous or undifferentiated carcinoma. The coexistence of a low-grade serous neoplasm and undifferentiated carcinoma can be regarded as a form of dedifferentiation. p53 was diffusely positive in 4 of 6 high-grade carcinomas, which raises the possibility that secondary Tp53 mutation is important in high-grade transformation in some of these cases. WT1 was negative in the 2 undifferentiated carcinomas, and PAX8 was positive in 1, suggesting that the latter marker is more useful in helping to confirm a Mullerian origin in dedifferentiated low-grade serous neoplasms. PMID- 22082604 TI - Vascular invasion in infiltrating ductal adenocarcinoma of the pancreas can mimic pancreatic intraepithelial neoplasia: a histopathologic study of 209 cases. AB - Although vascular invasion is a well-established indicator of poor prognosis for patients with infiltrating ductal adenocarcinoma of the pancreas (PDAC), the histopathologic characteristics of vascular invasion are not well described. Hematoxylin and eosin-stained slides from 209 surgically resected infiltrating PDACs were systematically evaluated for the presence or absence of microscopic vascular invasion. For the cases with vascular invasion, we further categorized the histologic pattern of invasion into conventional and pancreatic intraepithelial neoplasia-like (PanIN-like). In addition, several histopathologic factors in the surrounding blood vessels, including lymphocytic infiltration and luminal fibrosis, were carefully assessed. Data were compared with clinicopathologic variables, including patient survival. Microscopic vascular invasion was observed in 136 of the 209 PDACs (65.1%). Vascular invasion mimicking pancreatic intraepithelial neoplasia (PanIN-like invasion) was observed in 94 of the 136 cases (69.1%) with vascular invasion. Microscopic vascular invasion was associated with increased tumor size (P=0.04), higher pT classification (P=0.003), lymph node metastasis (P<0.0001), and perineural invasion (P=0.005). Vascular invasion was inversely correlated with neo-adjuvant therapy (P<0.0001). Examination of adjacent blood vessels revealed that peritumoral blood vessels with intimal lymphocytes (P=0.002), intimal (P=0.007) and medial (P=0.001) fibrosis, and cancer cells in vascular wall (P<0.0001) were all highly associated with the intraluminal vascular invasion. In univariate analysis, patients whose cancers had microscopic vascular invasion (median survival, 15.3 mo) had a significantly worse survival than did patients with carcinomas without vascular invasion (25.1 mo; P=0.01, log-rank test). Microscopic vascular invasion is a poor prognostic indicator and can histologically mimic PanIN. PMID- 22082605 TI - Diffuse cystic lung disease of unexplained cause with coexistent small airway disease: a possible causal relationship? AB - Diffuse "true" cystic lung disease is rare, and the specificity of high resolution computed tomography (HRCT) has reduced the need for biopsy. We present 5 patients with similar clinical and HRCT features of cystic lung disease that were sufficiently atypical to warrant surgical lung biopsies that showed coexistent small airway diseases (SAD). There were 4 female patients and 1 male patient with a mean age of 43 years. All were never smokers. Four had symptoms such as dyspnea (1), cough (2), or both (1). HRCTs showed variably sized thin walled cystic airspaces without zonal distribution, some with prominent vessels in their walls. One case was unilateral. Surgical lung biopsy showed cystic change comprising localized loss of alveolar density with coexistent SADs [chronic bronchiolitis (n=2), eosinophilic bronchiolitis, probable asthma (n=1), and diffuse idiopathic neuroendocrine cell hyperplasia (n=2)]. Two patients who were tested for Birt-Hogg-Dube-related gene mutations proved negative, and all lacked other features of Birt-Hogg-Dube. We hypothesize that chronic damage to small airways may lead to cystic degeneration in a minority of patients. Precedents in relation to Sjogren syndrome and hypersensitivity pneumonitis raise the possibility of a causal association between pathologies in these 2 anatomic compartments, although HRCT data in relation to common SADs indicate that this would be a rare phenomenon. The driving factor remains unknown. PMID- 22082606 TI - Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with "neuroblastoma-like" schwannomatosis and a novel germline SMARCB1 mutation. AB - Epithelioid malignant peripheral nerve sheath tumors arising in preexisting schwannomas are extremely rare. We report an unusual example occurring in a patient with multiple schwannomas (schwannomatosis), all but 1 of which showed "neuroblastoma-like" histology. By immunohistochemistry, both the epithelioid malignant peripheral nerve sheath tumor and the schwannomas showed a complete loss of the Smarcb1 protein. Subsequent genetic evaluation revealed the presence of a novel germline mutation in the SMARCB1/INI1 gene in the patient and in 3 of her children, 2 of whom were diagnosed with atypical teratoid/rhabdoid tumors of the brain. PMID- 22082608 TI - The prevalence of pancreatic acinar differentiation in gastric adenocarcinoma: report of a case and immunohistochemical study of 111 additional cases. AB - Although pancreatic acinar metaplasia in the gastric mucosa is well recognized in chronic gastritis, gastric carcinoma with acinar differentiation is very rare. We encountered a case of gastric adenocarcinoma with prominent histologic and immunohistochemical features of pancreatic acinar differentiation in the absence of identifiable heterotopic pancreatic tissue. Distinct glandular and diffuse patterns of adenocarcinoma were also present, and there was focal mucin production. The tumor strongly expressed pancreatic exocrine enzymes trypsin and chymotrypsin, and focal neuroendocrine staining was also present. To investigate the prevalence of acinar differentiation in histologically typical gastric cancers, we performed immunohistochemical staining for trypsin and chymotrypsin on a tissue microarray containing 111 conventional gastric adenocarcinomas (60 intestinal, 28 mixed, 22 diffuse type, and 1 undifferentiated). No obvious morphologic evidence of acinar differentiation was identified in any of the 111 cases. Although some cases showed equivocal staining for at least 1 pancreatic exocrine enzyme on the initial tissue microarray sections, repeat immunohistochemical staining on representative whole-tissue sections failed to reproduce positive staining. Thus, acinar differentiation is rare in gastric adenocarcinomas, other than in histologically unusual cases such as the one we report, and in others from the literature, which are reviewed. PMID- 22082607 TI - Atypical teratoid/rhabdoid tumor arising in a ganglioglioma: genetic characterization. AB - Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon, aggressive, embryonal pediatric brain tumor that almost always develops de novo and does not arise within, or evolve from, other brain tumor types. Although rhabdoid morphology can be seen in other tumor types, these are phenotypic mimics and, with only rare exceptions, do not manifest the INI-1 deletion at the 22q11.2 locus or the INI-1 nuclear protein loss that characterizes AT/RT. A few reports of AT/RT evolving from a low-grade ganglioglioma (GG) or pleomorphic xanthoastrocytoma have appeared. We present the case of a 6-year-old boy with a large right parietal mass whose tumor at initial presentation manifested 2 distinct components: GG with neoplastic neurons, low MIB-1 rate, and retention of INI-1 nuclear immunostaining (immunohistochemical) and, second, AT/RT with rhabdoid cells, polyphenotypic immunohistochemical expression, high MIB-1 rate, and loss of INI-1 nuclear expression. The 2 areas were separately assessed by fluorescence in situ hybridization for monosomy 22; monosomy 22 was identified in the AT/RT component but not in the GG areas. BRAF V600E mutation, a genetic abnormality seen in a significant percentage of pleomorphic xanthoastrocytomas and GGs, was assessed by polymerase chain reaction and identified in the tumor. Dual abnormalities of INI 1 loss and V600E BRAF mutation were identified in a cell culture line established from cerebrospinal fluid metastatic tumor cells. This cell line exhibited extremely rapid growth rate and rhabdoid morphology. Results suggest a postclonal modification in a subset of GG cells, with acquisition of INI-1 loss, confirming by biological methods what was previously suspected in rare reports of AT/RT evolving from other tumor types. PMID- 22082609 TI - Plasma gelsolin: a general prognostic marker of health. AB - Plasma gelsolin (pGSN) is the only component of two member extracellular actin scavenger system capable of severing circulating actin microfilaments. Here, we put forth the hypothesis that pGSN level is an important and sensitive general prognostic biomarker for health and disease conditions in humans, urging the need for gelsolin replacement therapy to improve patient's health status. Clinical significance and the therapeutic importance of this protein have been well illustrated in animal models as well as in patients with various diseases. Patients with decreased pGSN levels were observed to have higher mortality rate, longer hospital stay and longer ventilation time in intensive care units as compared to healthy controls. pGSN levels were found to be increasing in patients recovering from diseases; furthermore, it has been confirmed that repletion with exogenous recombinant pGSN increases the survival rate in animal models of different acute insults. To be used as a biomarker of health, however, establishing the accurate levels of gelsolin in human plasma and understanding its variance with age, race, gender and health status is a prerequisite. Upon establishing the accurate levels of pGSN in healthy individuals, this biomarker would predict the prognosis/disease progression in multiple health conditions and help in prioritizing the ones in-need of gelsolin replacement therapy. PMID- 22082610 TI - [Renal toxicity of contrast agents in oncologic patients]. AB - Cancer patients frequently undergo imaging examinations to diagnosis but also to evaluate their responses to treatment. These patients are also at high risk of kidney impairment before considering the possible nephrotoxicity of their chemotherapy. In this context, it is overriding to know contrast agents induced risks and what are the good practices to avoid them. Renal function evaluation takes a major part in there. The X-ray radiology using iodinated contrast agent (ICA) exposes patients to acute renal failure. This induced nephropathy is prevented by adequate hydration prior to injection when the glomerular filtration rate (GFR) of the patient is less than 60 ml/min/1.73 m(2). For hardly nephrotoxic, gadolinium-based contrast agents (GBCA) injected in magnetic resonance imaging, were considered for a long as a safe alternative to ICA. Yet they may induce nephrogenic systemic fibrosis (NSF). The recommendations of European and U.S. drugs safety agencies have recently converged defining groups at risk of NSF based on the level of patients GFR and the type of GBCA used. How to assess the risk-benefit balance of the cancer patient for whom you should choose an informative, effective and safe imaging examination? PMID- 22082611 TI - Facing Europe: visualizing spontaneous in-group projection. AB - Individuals perceive their own group to be more typical of a shared superordinate identity than other groups are. This in-group projection process has been demonstrated with both self-report and indirect measures. The two studies reported here extend this research to the visual level, specifically, within the domain of faces. Using an innovative reverse-correlation approach, we found that German and Portuguese participants' visual representations of European faces resembled the appearance typical for their own national identity. This effect was found even among participants who explicitly denied that one nation was more typical of Europe than the other (Study 1). Moreover, Study 2 provides experimental evidence that in-group projection is restricted to inclusive superordinate groups, as the effect was not observed for visual representations of a category ("Australian") that did not include participants' in-group. Implications for the in-group projection model, as well as for the applicability of reverse-correlation paradigms, are discussed. PMID- 22082612 TI - Body configuration modulates the usage of local cues to direction in biological motion perception. AB - The presence of information in a visual display does not guarantee its use by the visual system. Studies of inversion effects in both face recognition and biological-motion perception have shown that the same information may be used by observers when it is presented in an upright display but not used when the display is inverted. In our study, we tested the inversion effect in scrambled biological-motion displays to investigate mechanisms that validate information contained in the local motion of a point-light walker. Using novel biological motion stimuli that contained no configural cues to the direction in which a walker was facing, we found that manipulating the relative vertical location of the walker's feet significantly affected observers' performance on a direction discrimination task. Our data demonstrate that, by themselves, local cues can almost unambiguously indicate the facing direction of the agent in biological motion stimuli. Additionally, we document a noteworthy interaction between local and global information and offer a new explanation for the effect of local inversion in biological-motion perception. PMID- 22082613 TI - Effects of soya oligosaccharides and soya oligopeptides on lipid metabolism in hyperlipidaemic rats. AB - In the present study, we aimed to examine the effects of soya oligosaccharides (SOS) and soya oligopeptides (SOP) on blood lipid levels, release of vasoactive substances, antioxidant activity and faecal bile acid (FBA) excretion in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats were evenly divided into five groups according to diets as follows: regular diet (control), HFD, HFD enriched with 2 % of SOS (SOS), HFD enriched with 3 % of SOP (SOP) and HFD enriched with 2 % SOS and 3 % SOP (SOSP). The results showed that SOS and SOP significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, whereas HDL cholesterol concentration was significantly increased. Furthermore, SOS and SOP reduced plasma apoB, apoE and the apoB:apoAI ratio, whereas apoAI was significantly increased. Moreover, SOS and SOP also reduced plasma thromboxane A2 (TXA2) and the TXA2:prostacyclin (PGI2) ratio, whereas plasma PGI2 and nitric oxide were significantly increased. In addition, SOS and SOP significantly reduced serum and liver malondialdehyde concentrations and increased FBA excretion. However, we did not observe obvious influences of SOS and SOP on superoxide dismutase activities in the liver of HFD-fed rats. The combination of 2 % SOS and 3 % SOP showed a more marked effect than SOS or SOP alone in improving the lipid profile, release of vasoactive substances and increasing FBA excretion (P < 0.05). In summary, SOS and SOP might help prevent atherosclerosis through improving abnormal blood lipid levels, regulating vasoactive substances and protecting against oxidative stress. PMID- 22082614 TI - Does 18F-FDG uptake by respiratory muscles on PET/CT correlate with chronic obstructive pulmonary disease? AB - (18)F-FDG muscle uptake is evident in some benign physiologic processes as seen in the respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) and labored breathing. The purpose of this study was to correlate the presence of COPD with the patterns of (18)F-FDG uptake by muscles as demonstrated by PET/CT scans. METHODS: (18)F-FDG PET/CT scans and pulmonary function tests (PFTs) were performed for 63 consecutive patients with newly diagnosed or highly suspected lung cancer. Presurgical pulmonary function tests by way of spirometry examinations were performed as the standard of care. Patients were grouped into those with normal spirometry findings and those with mild to very severe COPD. The guidelines of the Global Initiative for Chronic Obstructive Lung Disease were used for staging COPD and obstructive impairment. A nuclear medicine physician and 2 residents who did not know the COPD status retrospectively reviewed PET/CT scans and kept a log for cases of increased (18)F-FDG uptake in the respiratory muscles (diaphragm, intercostal muscles, and scalene muscles). The chi(2) test and Cramer V were used to evaluate the correlation between increased (18)F-FDG uptake by muscles and the presence of COPD. RESULTS: Sixty-three patients underwent both (18)F-FDG PET/CT and PFT within 1 mo of each another without interval therapy. Of the 63 patients, 26 (41%) had no spirometric obstruction and 37 (59%) had spirometric obstruction. Of these, 30 (81%) had a previously established diagnosis of COPD (1 mild, 26 moderate, 9 severe, and 1 very severe). Excessive (18)F-FDG uptake was seen in at least 2 of the 3 muscles (diaphragm and intercostal muscles) in 27 (73%) of the 37 patients with COPD and obstructive ventilatory impairment. The severity of COPD and obstruction showed a significant correlation with the presence of abnormal (18)F-FDG uptake by any of the 3 muscle types, particularly when 2 groups of muscles were involved (Cramer V = 0.60, chi(2) P < 0.001). CONCLUSION: Our study revealed a strong correlation between increased (18)F-FDG uptake by respiratory muscles and the presence of COPD. PMID- 22082616 TI - Co-morbidities associated with tuberculosis in an autopsy case series. AB - A retrospective review of cases of tuberculosis examined by our Autopsy Division was undertaken to determine the most common associated co-morbidities. Forty-six cases of tuberculosis were examined between 2000 and 2010. The subpopulation of decedents studied included a large number of incarcerated individuals and showed an age distribution from 30 to 78 years. Thirty-five of the cases reviewed showed one or more co-morbidities, primarily viral hepatitis C, cancer, human immunodeficiency virus (HIV), cardiovascular diseases, and chronic obstructive pulmonary diseases. Almost 30% of the cases showed evidence of extrapulmonary disease, including one case of tuberculous meningitis. In approximately 20% of the cases, rapid progressive or disseminated tuberculosis was identified as immediate cause of death. Tuberculosis was the immediate cause of death in 20% of the hepatitis C-infected group and in 14% of the decedents diagnosed with cancer, compared to over 45% of the HIV-infected decedents. This observation is consistent with previous studies reporting an enhanced mortality from tuberculosis in HIV-infected subjects. Interestingly, rapid progressive tuberculosis was identified as immediate cause of death in two cases with no associated co-morbidities; both decedents were young immunocompetent adults, suggesting an increasing susceptibility of this subpopulation to tuberculosis exposure and to severe disease. PMID- 22082615 TI - The DeltafbpA attenuated candidate vaccine from Mycobacterium tuberculosis, H37Rv primes for a stronger T-bet dependent Th1 immunity in mice. AB - The DeltafbpA candidate vaccine derived from Mycobacterium tuberculosis (H37Rv) (Mtb) protects mice better than BCG against tuberculosis, and we investigated the hypothesis that DeltafbpA may induce a stronger Th1 immunity. Since T-bet transcription factor regulates Th1 immunity, mice infected with DeltafbpA, BCG vaccine and related mycobacteria were analyzed for T-bet positive T cells. Mouse dendritic cells (DCs) or macrophages were also pulsed with excretory-secreted antigens (ES; Antigen-85B, ESAT-6 and CFP10) and cocultured with T cells from immunized or naive mice and tested for in vitro induction of T-bet and IFN-gamma. In both models, DeltafbpA mutant induced a stronger response of T-bet(+)CD4 T cells, which correlated with an increased expansion of IFN-gamma(+)CD4 T cells in vivo and in vitro. When DCs pulsed with ES antigens were allowed to stimulate T cells, ESAT-6 and CFP-10 failed to induce a recall expansion of T-bet(+)IFN gamma(+)CD4 T cells from BCG vaccinated mice. Thus, deletion of RD1 in BCG seems to reduce its ability to induce T-bet and induce stronger Th1 immunity. Finally, mice were vaccinated with DeltafbpA and BCG and challenged with virulent Mtb for evaluation of protection and T cell expansion. DeltafbpA vaccinated mice showed a rapid and stronger expansion of CD4(+)CXCR3(+) IFN-gamma(+) T cells in the lungs of Mtb challenged mice, compared to those which had BCG vaccine. DeltafbpA immunized mice also showed a better decline of the Mtb bacterial counts of the lungs. Mtb derived DeltafbpA candidate vaccine therefore induces qualitatively better T-bet dependent Th1 immunity than BCG vaccine. PMID- 22082617 TI - On the pathogenesis of post primary tuberculosis: the role of bronchial obstruction in the pathogenesis of cavities. AB - Mycobacterium tuberculosis produces two distinct types of disease: primary and post primary tuberculosis. We recently reported that post primary tuberculosis begins in immunocompetent adults as an endogenous lipid pneumonia that abruptly undergoes necrosis to produce cavities. Obstruction of bronchi by endobronchial tuberculosis is a consistent finding in developing post primary tuberculosis. This paper reports a case of obstructive pneumonia caused by cancer that underwent rapid necrosis to produce a cavity that was similar to those produce by tuberculosis. Analysis of this case with the relevant literature supports the hypothesis that bronchial obstruction is an essential contributor to the development of post primary tuberculosis and that it may help explain the localized suppression of host defense mechanisms in adult pulmonary tuberculosis. PMID- 22082618 TI - Anti-inflammatory effect with high intensity focused ultrasound-mediated pulsatile delivery of diclofenac. AB - A pulsatile ultrasound controlled drug release platform with diclofenac-loaded alginate microcapsules (fabricated with a home-made electrostatic device, 75% embedded rate) was established to evaluate anti-inflammation efficiency. Better anti-inflammation efficiency was found using the ultrasound system and the drug delivery can be adjusted based on the programmed ultrasound cycle. The results of the in vitro study show that an approx. 30% higher drug release rate was obtained by using continuous ultrasound irradiation (9-Watt, 180 min), and an approx. 16% higher drug release rate was obtained by using pulsatile ultrasound irradiation (9-Watt, 60 min) compared to without ultrasound activation. For the in vivo study, the anti-inflammatory test with carrageenan-induced rat's paw edema shows that diclofenac-loaded microcapsules followed by ultrasound irradiation (9-Watt, 60 min) contributed to an 81% inhibition rate, which was significantly higher than diclofenac only (approx. 60% higher). In addition, because of their heat conducting properties, gold nanoparticles encapsulated in the diclofenac-loaded microcapsules resulted in better drug release efficiency, but tended to depress the anti-inflammation effect. PMID- 22082619 TI - The role of microstructured and interconnected pore channels in a collagen-based nerve guide on axonal regeneration in peripheral nerves. AB - The use of bioengineered nerve guides as alternatives for autologous nerve transplantation (ANT) is a promising strategy for the repair of peripheral nerve defects. In the present investigation, we present a collagen-based micro structured nerve guide (Perimaix) for the repair of 2 cm rat sciatic nerve defects. Perimaix is an open-porous biodegradable nerve guide containing continuous, longitudinally orientated channels for orientated nerve growth. The effects of these nerve guides on axon regeneration by six weeks after implantation have been compared with those of ANT. Investigation of the regenerated sciatic nerve indicated that Perimaix strongly supported directed axon regeneration. When seeded with cultivated rat Schwann cells (SC), the Perimaix nerve guide was found to be almost as supportive of axon regeneration as ANT. The use of SC from transgenic green-fluorescent-protein (GFP) rats allowed us to detect the viability of donor SC at 1 week and 6 weeks after transplantation. The GFP-positive SC were aligned in a columnar fashion within the longitudinally orientated micro-channels. This cellular arrangement was not only observed prior to implantation, but also at one week and 6 weeks after implantation. It may be concluded that Perimaix nerve guides hold great promise for the repair of peripheral nerve defects. PMID- 22082621 TI - Hydrophobic polycationic coatings that inhibit biofilms and support bone healing during infection. AB - Adhesion of microorganisms to biomaterials with subsequent formation of biofilms on such foreign bodies as orthopedic trauma hardware is a critical factor in implant-associated infections; once a biofilm has been established, its microorganisms become recalcitrant to the host's immune surveillance and markedly resistant to drugs. We have previously reported that painting with the hydrophobic polycation N,N-dodecyl,methyl-PEI (PEI = polyethylenimine) renders solid surfaces bactericidal in vitro. Herein we observe that N,N-dodecyl,methyl PEI-derivatized titanium and stainless steel surfaces resist biofilm formation by Staphylococcus aureus compared to the untreated ones. Using imaging, microbiology , histopathology-, and scanning electron microscopy (SEM) experiments in a clinically relevant large-animal (sheep) trauma model, we subsequently demonstrate in vivo that orthopedic fracture hardware painted with N,N dodecyl,methyl-PEI not only prevents implant colonization with biofilm but also promotes bone healing. Functionalizing orthopedic hardware with hydrophobic polycations thus holds promise in supporting bone healing in the presence of infection in veterinary and human orthopedic patients. PMID- 22082620 TI - Effect of oligonucleotide mediated immobilization of bone morphogenic proteins on titanium surfaces. AB - The aim of the present study was to test the hypothesis that oligonucleotides can be used for anchorage and slow release of osteogenic growth factors such as BMP to enhance the osteogenic activity of a titanium implant surface. Strands of 60 mer non-coding DNA oligonucleotides (ODN) were bound to an acid-etched sandblasted cp Ti-surface by nanomechanical fixation using anodic polarization. RhBMP2 that had been conjugated to complementary strands of DNA oligonucleotides was then bound to the anchored ODN strands by hybridization. Binding studies showed a higher binding capacity compared to non-conjugated BMP2. Long term release experiments demonstrated a continuous release from all surfaces that was lowest for the conjugated BMP2 bound to the ODN anchor strands. Proliferation of human bone marrow stroma cells (hBMSC) was significantly increased on these surfaces. Immunofluorescence showed that hBMSC grown on surfaces coated with specifically bound conjugated BMP2 developed significantly higher numbers of focal adhesion points and exhibited significantly higher levels of transcription of osteogenic markers alkaline phosphatase and osteopontin at early intervals. Biological activity (induction of alkaline phosphatase) of conjugated BMP2 released from the surface was comparable to released non-conjugated BMP2, indicating that conjugation did not negatively affect the activity of the released molecules. In conclusion the present study has shown that BMP2 conjugated to ODN strands and hybridized to complementary ODN strands anchored to a titanium surface has led to slow growth factor release and can enhance the osteogenic activity of the titanium surface. PMID- 22082622 TI - L-eye to me: the combined role of Need for Cognition and facial trustworthiness in mimetic desires. AB - Recent studies showed that stimuli are evaluated more favourably when they are perceived to capture others' attention, an effect coined "mimetic desire". The aim of the present research was to examine the combined role of Need for Cognition and target's facial trustworthiness in this effect. Participants saw movie excerpts of trustworthy and untrustworthy 3D faces (Oosterhof & Todorov, 2008) turning their attention towards one art painting and away from another art painting. Results showed that looked-at paintings were preferred to looked-away paintings when associated with a trustworthy face. However, the reversed finding was observed for paintings associated with untrustworthy faces. The latter interaction was in turn moderated by participant's Need for Cognition, with a larger reversal effect for participants scoring lower on the NFC scale. Theoretical implications of these findings are discussed. PMID- 22082623 TI - Sharing transnational experiences of psychogeriatric units dedicated to the management of behavioral and psychological symptoms in demented patients. PMID- 22082624 TI - Occipitocervical fusion. AB - The evolution of occipitocervical fixation and new rigid universal screw-rod construct technology has allowed secure anchorage at each level of the occipitocervical junction with the elimination of rigid external orthoses. Rigid occipitocervical instrumentation constructs have achieved higher fusion rates and less postoperative immobilization-associated complications. Outcomes have improved compared with former nonrigid instrumentation techniques; however, with advances of rigid occipitocervical stabilization capability have come new challenges, risks, and operative techniques. A thorough understanding of the relevant cervical bony and soft tissue anatomy is essential for safe implantation and a successful outcome. PMID- 22082625 TI - C1-C2 posterior fixation: indications, technique, and results. AB - The atlantoaxial motion segment, which is responsible for half of the rotational motion in the cervical spine, is a complex junction of the first (C1) and second (C2) cervical vertebrae. Destabilization of this joint is multifactorial and can lead to pathologic motion with neurologic sequelae. Posterior spinal fixation of the C1-C2 articulation in the presence of instability has been well described in the literature. Early reports of interspinous/interlaminar wiring have evolved into modern-day pedicle screw/translaminar constructs, with excellent results. The success of a C1-C2 posterior fusion rests on appropriate indications and surgical techniques. PMID- 22082626 TI - Subaxial cervical and cervicothoracic fixation techniques--indications, techniques, and outcomes. AB - The subaxial and cervicothoracic junction is a relatively difficult area for spine surgeons to navigate. Because of different transitional stressors at the junction of the smaller cervical vertebrae and the larger thoracic segments, proximity to neurovascular structures, and complex anatomy, extreme care and precision must be assumed during fixation in these regions. Lateral mass screws, pedicle screws, and translaminar screws are currently the standard of choice in the subaxial cervical and upper thoracic spine. This article addresses the relevant surgical anatomy, pitfalls, and pearls associated with each of these fixation techniques. PMID- 22082627 TI - Posterior surgery for cervical myelopathy: indications, techniques, and outcomes. AB - This article details the controversies associated with the different treatment strategies in patients with cervical spondylotic myelopathy. The natural history, incidence, pathophysiology, physical examination, and imaging findings are discussed followed by the indications, techniques, and outcomes of patients treated with posterior cervical decompression via decompressive laminectomy, laminectomy and instrumented fusion, and laminoplasty. PMID- 22082628 TI - Anterior approach for complex cervical spondylotic myelopathy. AB - Cervical spondylotic myelopathy (CSM) is a slowly progressive disease resulting from age-related degenerative changes in the spine that can lead to spinal cord dysfunction and significant functional disability. The degenerative changes and abnormal motion lead to vertebral body subluxation, osteophyte formation, ligamentum flavum hypertrophy, and spinal canal narrowing. Repetitive movement during normal cervical motion may result in microtrauma to the spinal cord. Disease extent and location dictate the choice of surgical approach. Anterior spinal decompression and instrumented fusion is successful in preventing CSM progression and has been shown to result in functional improvement in most patients. PMID- 22082629 TI - Management of adjacent segment disease after cervical spinal fusion. AB - Adjacent segment disease (ASD) was described after long-term follow-up of patients treated with cervical fusion. The term describes new-onset radiculopathy or myelopathy referable to a motion segment adjacent to previous arthrodesis and often attributed to alterations in the biomechanical environment after fusion. Evidence suggests that ASD affects between 2% and 3% of patients per year. Although prevention of ASD was one major impetus behind the development of motion sparing surgery, the literature does not yet clearly distinguish a difference in the rate of ASD between fusion and disk replacement. Surgical techniques during index surgery may reduce the rate of ASD. PMID- 22082630 TI - Esophageal and vertebral artery injuries during complex cervical spine surgery- avoidance and management. AB - Vertebral artery and esophageal injuries are rare but feared complications of cervical spine surgery. Appropriate understanding of treatment algorithms for prompt intervention in the event of a vertebral artery injury minimizes the risk of exsanguination and/or profound neurologic consequences. Esophageal injuries are often more subtle, and although intraoperative injuries can sometimes be diagnosed at the time of surgery, they frequently do not present until the week after surgery. They can additionally be seen as a late complication of instrumentation usage and/or failure. Expedient diagnosis and management of these injuries minimize their impact and allow for optimal treatment outcome. PMID- 22082631 TI - Diagnosis and management of metastatic cervical spine tumors. AB - The bony spine is overall the third most common site for distant cancer metastasis, with the cervical spine involved in approximately 8 to 20% of metastatic spine disease cases. Diagnosis and management of metastatic spine disease requires disease categorization into the compartment involved, pathology of the lesion, and anatomic region involved. The diagnostic approach should commence with careful physical examination, and the workup should include plain radiographs, magnetic resonance imaging, computed tomography, and bone scintigraphy. Management ranges from palliative nonoperative to aggressive surgical treatment. Optimal management requires proper patient selection to individualize the most appropriate treatment modality. PMID- 22082632 TI - Management of cervical spine trauma: can a prognostic classification of injury determine clinical outcomes? AB - Although the management of cervical spine trauma is relatively complex, multiple classification systems have attempted to simplify it through the use of descriptive terms. Most historical classification systems failed to yield sufficient prognostic information to guide clinical treatment until the Subaxial Injury Classification system was developed. This classification system takes into account the injury morphology, discoligamentous complex, and the most important prognostic factor, neurologic status. The early results of this classification system have been encouraging and it is expected to improve spinal trauma care through enhancing more uniform nomenclature and communication for surgeons managing spinal trauma. PMID- 22082633 TI - Cervical total disk replacement: complications and avoidance. AB - Anterior cervical diskectomy and fusion for neurologic deficits, radicular arm pain, and neck pain refractory to conservative management are successful. The approach and procedure were first described in 1955 and have become the anterior cervical standard of care for orthopedic surgeons and neurosurgeons. Advancements and innovations have addressed disease processes of the cervical spine with motion-preserving technology. The possibility of obtaining anterior cervical decompression while maintaining adjacent segment motion led to the advent of cervical total disk replacement. The Food and Drug Administration has approved 3 cervical devices with other investigational device exemption trials under way. PMID- 22082634 TI - Surgical management of complex spinal deformity. AB - Surgical treatment of complex cervical spinal deformities can be challenging operations. Patients often present with debilitating conditions ranging from generalized decreased quality of life to quadriplegia. Surgical treatment can be divided into anterior, posterior, or combined procedures. A thorough understanding of anatomy, pathology, and treatment options is necessary. This article focuses on the surgical treatment of complex spinal deformity. PMID- 22082635 TI - Revision cervical spine surgery. AB - Principles of revision cervical spine surgery are based on adequate decompression of neural elements and mechanical stability via appropriate selection of surgical approach and constructs producing long-term stability with arthrodesis. When planning revision surgery, the surgeon must consider the cause of the underlying problem (eg, biological, mechanical), the potential for complications, and clinical outcomes that can reasonably be expected. This information should be clearly explained to the patient during the informed consent process. This article provides the spine care provider with an understanding of how to appropriately evaluate and manage the most common cervical conditions that require revision cervical spine surgery. PMID- 22082636 TI - Minimally invasive approaches to the cervical spine. AB - Minimally invasive approaches and operative techniques are becoming increasingly popular for the treatment of cervical spine disorders. Minimally invasive spine surgery attempts to decrease iatrogenic muscle injury, decrease pain, and speed postoperative recovery with the use of smaller incisions and specialized instruments. This article explains in detail minimally invasive approaches to the posterior spine, the techniques for posterior cervical foraminotomy and arthrodesis via lateral mass screw placement, and anterior cervical foraminotomy. Complications are also discussed. Additionally, illustrated cases are presented detailing the use of minimally invasive surgical techniques. PMID- 22082637 TI - Treatment of complex cervical spine disorders. Preface. PMID- 22082638 TI - Antiangiogenic therapy of breast cancer: how did we get here?: the road not taken. PMID- 22082639 TI - Heterogeneity of breast cancer: etiology and clinical relevance. AB - Cancer progression is a dynamic process of clonal adaptation to changing microenvironments. From the single founder cell until the clinical detection of tumours, there are consecutive clonal expansions and a constant acquisition of genetic and epigenetic alterations, events that contribute to the generation of intra-tumor heterogeneity. In breast cancer intra-tumor heterogeneity can arise from the differentiation of stem-like cells along with the clonal selection during tumor progression, and represents a major challenge for the design of effective therapies. To infer breast cancer progression and its response to particular treatments it is important to understand the origins of the inter- and intra-tumor heterogeneity and the forces that control tumor evolution. Insights about the evolution of breast cancer heterogeneity would contribute to the design of most effective therapeutic strategies to target the tumors at single clon level. This review is intended to give a general overview about the origins of breast cancer heterogeneity and its impact in the clinical management of the disease. PMID- 22082640 TI - Treatment for ALK-mutated non-small-cell lung cancer: a new miracle in the research race. AB - The discovery of anaplastic lymphoma kinase (ALK) rearrangements in a subset of patients with nonsmall- cell lung cancer (NSCLC) and its potential blockage by specific inhibitors such as crizotinib has been one of the latest advances in the treatment of this disease. In this article, we will review the most important clinical aspects of ALK alterations in NSCLC patients and the pending questions to answer: the most effective means of diagnosing ALK-rearranged NSCLC, and efficacy, toxicity profile and potential mechanisms of resistance to crizotinib. PMID- 22082641 TI - Non-FDG PET in oncology. AB - Although FDG PET and PET/CT have a well established role in the management of most cancer patients, they also have some limitations. For the last 15-20 years a growing number of non-FDG PET tracers have been used in research. Many of these new PET tracers are being investigated for the non-invasive assessment of different biologic functions in cancer cells. This unique information should contribute to making personalized cancer therapy a reality. This paper reviews the non-FDG PET tracers that are most likely to find clinical application, some of them in the near future. PMID- 22082642 TI - A new era in the treatment of melanoma: from biology to clinical practice. AB - Melanoma is the deadliest cutaneous malignancy and its incidence continues to grow. Until 2011, the treatment options for metastatic melanoma were scarce and without any overall survival benefit. The emergence of new targeted therapies for BRAF mutant melanoma (vemurafenib) and immunotherapy (ipilimumab) has changed the standard of care for this disease. The objective of the present review is to summarise the biological background of the new therapeutic approaches in melanoma, focusing on apoptosis resistance, immune modulation and angiogenesis, and the direct translation into clinical practice. PMID- 22082643 TI - Ameloblastoma, a rare benign odontogenic tumour: an interesting tumour review targeting the role of radiation therapy. AB - Ameloblastoma is known as a benign, slow-growing, rare, odontogenic neoplasm. The solid/multicystic, the unicystic with a fibrous connective-tissue capsule and the peripheral ameloblastoma represent the three well distinguished clinical types of ameloblastoma. Surgical resection with an attempt to achieve adequate free margins constitutes a well documented and accepted treatment modality. Controversies exist, however, with regard to the extent of operative intervention. Patients with inadequate or positive surgical margins or unresectable lesions can be treated with radiation or combined radiation and chemotherapy. The authors present a review of this sparse disease focusing on the special role and efficacy of radiation therapy in its management. PMID- 22082644 TI - Recommendations and expert opinion on the adjuvant treatment of colon cancer in Spain. AB - Adjuvant chemotherapy is the current standard in the management of patients with localised colon cancer (CC) following curative resection. The use of oxaliplatin plus 5 fluorouracil/leucovorin (FOLFOX) or oxaliplatin plus capecitabine-based (XELOX) regimens, both approved in Europe as adjuvant treatment for stage III CC, has improved prognosis in this stage, but questions on their usefulness in high risk stage II or elderly CC patients and on the role of some prognostic biomarkers are still pending. In April 2010, a consensus meeting on adjuvant CC treatment based on a revision of the most recent literature was held in Spain. The panel considered the use of adjuvant chemotherapy for high-risk stage II CC patients to be justified. Additionally, the more convenient administration of oral fluoropyrimidines vs. IV continuous infusion 5-FU would make XELOX a more suitable alternative for the patient. A more cautious decision should be taken when prescribing oxaliplatin treatment in patients aged >=70. PMID- 22082645 TI - VEGF-A-independent and angiogenesis-dependent tumour growth in patients with metastatic breast cancer. AB - BACKGROUND The mechanisms of tumour progression during anti-VEGF-A treatment are poorly understood. PATIENTS AND MATERIALS Two patients with metastatic breast cancer are described who developed new metastases while receiving anti-VEGF-A treatment. Angiogenic parameters were determined by CD34/Ki67 double staining, Chalkley counts (CC) and endothelial cell proliferation fractions (ECP). RT-PCR Taqman low-density arrays with a gene panel of 94 angiogenesis-related genes were performed on both metastases and compared to 10 unselected primary breast tumours. RESULTS Both lesions showed a high and intermediate CC of, respectively, 7.5+/-0.62 and 4.8+/-0.2. Both lesions had elevated ECP values of 14% and 8%. Low density array screening showed that VEGFR1 mRNA was overexpressed in both samples (z-score=7.85 and 7.81) compared to control samples (out of range [min-max]). Additional analysis confirmed this finding at the protein level by immunohistochemistry. CONCLUSION These observations suggest that tumour progression under continuous anti-VEGF-A continues to be angiogenesis dependent. Further exploration is needed to identify the mechanisms of anti-VEGF-A resistance in order to design combination-targeted therapies. PMID- 22082646 TI - Fine-needle aspiration cytopathology in the diagnosis of Wilms tumor. AB - BACKGROUND/PURPOSE The International Society of Paediatric Oncology (SIOP) protocol for Wilms tumor (WT) includes preoperative chemotherapy as the initial approach. However, an inadequate treatment may be performed in case of histological misdiagnosis. We evaluated the impact of fine-needle aspiration cytopathology (FNAC) in the diagnosis of unilateral WT in our group of patients. MATERIALS AND METHODS A retrospective descriptive study of patients with diagnosis of unilateral WT who underwent FNAC prior to neoadjuvant chemotherapy between 1993 and 2009 was performed. We reviewed the cytological diagnosis obtained by ultrasound-guided FNAC and the histological correlation with the resected specimens. RESULTS FNAC was performed in 66 patients with unilateral WT. In 57 of the 58 patients with positive FNAC for WT, the final diagnosis was correct (PPV: 98.2%). In 8 cases with negative FNAC for WT, the final diagnosis was positive for WT in 3 patients (NPV: 62.5%). Sensitivity was 95% and specificity was 83.3%. No complications were found associated with the procedure, except for an episode of haematuria, which resolved spontaneously. CONCLUSIONS FNAC is a useful and feasible technique in children that may confirm the suspected diagnosis of unilateral WT, avoiding inadequate preoperative chemotherapy in case of a non-Wilms renal tumor. PMID- 22082647 TI - Epidermal growth factor receptor (EGFR) mutations in a series of non-small-cell lung cancer (NSCLC) patients and response rate to EGFR-specific tyrosine kinase inhibitors (TKIs). AB - INTRODUCTION Epidermal growth factor receptor (EGFR) mutation related to tyrosine kinase inhibitors' (TKIs) responsiveness in non-small cell lung cancer (NSCLC) has become an important issue for therapeutic decision-making in NSCLC patients. MATERIAL AND METHODS Sixty-nine Caucasian NSCLC patients were screened for mutations in the tyrosine kinase (TK) domain of EGFR by direct sequencing from December 2005 to September 2010. RESULTS Activating mutations in the EGFR TK domain were found in 8 of 69 (11.6%) (7 deletions in exon 19 and one L858R mutation in exon 21). Seven of those mutations were found in adenocarcinoma and one mutation in bronchiolo-alveolar carcinoma; five of them in females (one smoker) and three of them in males (one smoker). All patients carrying activating mutations in the TK domain of EGFR were treated with TKIs. Ten patients not carrying an activating mutation in EGFR, who progressed after chemotherapy, were also treated with compassionate use of EGFR-specific TKIs (gefitinib or erlotinib). An objective response (partial response) was observed in all patients carrying an activating mutation in EGFR that received TKIs. Median overall survival for these patients has not been reached, however mean survival has been estimated at 39.5 months (95% CI, 22-57). CONCLUSIONS As previously reported, EGFR TK mutational analysis was a predictive test for response to targeted therapy with EGFR TKIs. The early identification of these patients consistently attains disease response and clearly improves outcomes. PMID- 22082648 TI - Uncertainties and CTV to PTV margins quantitative assessment using cone-beam CT technique in clinical application for prostate, and head and neck irradiation tumours. AB - PURPOSE To evaluate the magnitude of systematic and random errors from a subset of 100 prostate and 26 head and neck (H&N) cancer patients treated with conventional conformal radiotherapy and using image-guided radiotherapy (IGRT). After treatment, the uncertainties involved and the CTV to PTV margin were evaluated. MATERIAL AND METHODS An Elekta Synergy(r) linear accelerator was used, taking advantage of 3D on-board computed tomography. IGRT with no-action level (NAL) protocol was applied, reporting the 3D translation and rotation corrections. A statistical study was performed to analyse systematic, random and interobserver uncertainties, and, finally, to obtain the CTV to PTV margins. RESULTS The H&N patients' uncertainties found were smaller than those of prostate patients. The CTV to PTV margins assessed, following the guidelines found in the literature, in the three dimensions of space (right-left, superior-inferior, anterior-posterior) were (5.3, 3.5, 3.2) mm for H&N and (7.3, 7.0, 9.0) mm for prostate cancer treatments. CONCLUSIONS It was found that assessing all the involved uncertainties within radiation treatments was very revealing; their quality improves using IGRT techniques and performing extensive data analysis. PMID- 22082649 TI - Immunohistochemical expression of excision repair cross-complementing 1 (ERCC1) in non-small-cell lung cancer: implications for patient outcome. AB - INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13+/-2 months) than in those with ERCC1-negative tumours (27+/-5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20+/-3 months) than in those with ERCC1 negative tumours (33+/-5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients. PMID- 22082650 TI - Sexual maturation and aging of adult male mealybug (Hemiptera: Pseudococcidae). AB - The physiological age of adult males of seven mealybug species was measured in relation to the elongation of the male pair of the waxy caudal filaments. These filaments begin to emerge after eclosion and reached their maximum length from 29.4-46.6 h. The studied males were divided into three age groups, expressed as percentages of the total waxy caudal filaments length. Attraction to a sex pheromone source was significantly higher in the oldest male group (maximum filaments growth) compared with youngest one. Only the oldest male group copulated successfully; few of the younger males tested displayed 'courtship' behavior towards conspecific virgin females. The calculated duration of the sexually active phase of the adult male life cycle varied among species ranging from 34.4 to 46.6 h. There were marked variations in the strength of attraction to a pheromone source according to time of day. There was a continuous decrease in sexual activity from morning to evening. Our findings reveal clear maturation periods for adult males of the seven studied species. The long immature phase of the adult male mealybug is probably also related to several physiological processes that are needed to complete male maturation. The most noticeable change is the elongation of the waxy caudal filaments. However, mating may be performed at any time ambient conditions are suitable. Whereas male mealybug flight towards a pheromone source is restricted to a few hours, the male may continue mating activity throughout its sexually active period. PMID- 22082651 TI - At-line prediction of fatty acid profile in chicken breast using near infrared reflectance spectroscopy. AB - Near infrared reflectance (NIR) spectroscopy was evaluated as at-line technique to predict FA profile of chicken breast directly at the slaughterhouse. Intact breasts of 214 chickens were scanned by applying a fiber optic probe to the Pectoralis superficialis muscle. Meat samples were analyzed by gas chromatography as the reference method for the determination of FA composition. Calibration equations were developed considering NIR wavelengths between 1100 and 1830nm, and modified partial least square (MPLS) was chosen as the chemometrics method to perform the calibrations. Different mathematical pre-treatments were tested and the best calibration equation for each FA was retained. Near infrared reflectance spectroscopy did not result in satisfactory predictions of FA. The best predictions were observed for oleic acid (C18:1n-9), monounsaturated FA (MUFA), and polyunsaturated FA (PUFA), and for a few minor FA. Results suggest that for chicken breast muscle, a lean meat, it was not possible to predict FA using NIR spectroscopy as an at-line technique in the abattoir. PMID- 22082652 TI - Association of ABCC10 polymorphisms with nevirapine plasma concentrations in the German Competence Network for HIV/AIDS. AB - BACKGROUND: Nevirapine exhibits marked interpatient variability in pharmacokinetics. CYP2B6 activity and demographic factors are important, but there are a few data on drug transporters for nevirapine. ABCC10 (MRP7) is an efflux transporter highly expressed in liver, intestine, and peripheral blood cells. We investigated whether nevirapine is a substrate for ABCC10 and whether genetic variants contribute to variability in nevirapine plasma concentrations. METHODS: Accumulation of nevirapine was assessed in parental and ABCC10 transfected HEK293 cells (HEK293-ABCC10), CD4+ cells, and monocyte-derived macrophages from healthy volunteers (n=8). ABCC10 small interfering RNA studies were also conducted. DNA samples with paired plasma drug concentrations were available from 163 HIV-infected patients receiving nevirapine-containing regimens. Sequenom was used to screen 14 single nucleotide polymorphisms in ABCC10. Linear regression models were used to identify factors independently associated with nevirapine plasma concentration. RESULTS: Nevirapine accumulation was 37% lower in HEK293-ABCC10 cells compared with parental HEK293 cells (P=0.02), and this was reversed by cepharanthine (an ABCC10 inhibitor). After small interfering RNA knockdown of ABCC10, there was an increase in accumulation of nevirapine in CD4 cells (32%; P=0.03) and monocyte-derived macrophages (38%; P=0.04). Marked differences in the haplotype structure of ABCC10 was observed between White and Black patients in the cohort. In Whites, an exonic single nucleotide polymorphism (rs2125739) was significantly associated with nevirapine plasma concentration (P=0.02). Multivariate regression analysis identified carriage of a composite genotype of ABCC10 rs2125739 and CYP2B6 516G>T (P=0.001), time post dose (P=0.01) and BMI (P=0.07) to be independently associated with nevirapine plasma concentrations. CONCLUSION: Nevirapine is a substrate for ABCC10 and genetic variants influence its plasma concentrations. ABCC10 in lymphocytes and macrophages may also contribute to variability in intracellular permeation of nevirapine. Further studies are required to determine the clinical implications of these findings. PMID- 22082654 TI - The GNB3 C825T polymorphism influences platelet aggregation in human whole blood. AB - BACKGROUND: Platelet aggregation varies among individuals; and genetic factors may alter platelet activation through G-protein-coupled receptors, thus influencing results of point-of-care platelet aggregometry in whole blood. We tested the hypothesis that the C825T polymorphism of the gene GNB3 encoding the G protein beta-3 subunit and the platelet GPIIIa Pl(A1)/(A2) polymorphism of the glycoprotein IIIa influence platelet aggregation. METHODS: Evoked [thrombin receptor activating peptide (TRAP), ADP, TXA(2) agonist U46619, epinephrine, and collagen] platelet aggregation in whole blood was measured using impedance aggregometry (Multiplate) in 143 healthy individuals (age: 40.2 years +/-11.7 SD). Genotypes were determined using pyrosequencing and restriction analysis. Data were analyzed by linear one-way analysis of variance and Student's t-test, linear and multiple regression, and the chi(2)-test, as appropriate. RESULTS: Homozygous carriers of the GNB3 825C-allele showed significantly (P<=0.022) increased maximum aggregation for EC(75) dosages compared with CT and TT genotypes [e.g. ADP: CC 150+/-36 vs. TT 126+/-33 aggregation unit (AU); thrombin receptor activating peptide: CC 175+/-46 vs. TT 150+/-38 AU; U46619: CC 164+/-33 vs. 149+/-32 AU; epinephrine: CC 66+/-41 vs. TT 48+/-34 AU]. In contrast, genotypes of glycoprotein IIb/IIIa PI(A)-polymorphism had no effect. Regression analysis revealed the GNB3 C825T polymorphism as an independent factor for enhanced platelet aggregation, besides factors such as female sex and blood cell values. CONCLUSION: In human whole blood, the GNB3 825CC genotype is associated with enhanced platelet aggregation. PMID- 22082653 TI - Effects of vitamin A and D receptor gene polymorphisms/haplotypes on immune responses to measles vaccine. AB - OBJECTIVE: Vitamins A and D, and their receptors, are important regulators of the immune system, including vaccine immune response. We assessed the association between polymorphisms in the vitamin A receptors [retinoic acid receptor alpha, retinoic acid receptor beta (RARB), and retinoic acid receptor gamma] and vitamin D receptor (VDR)/retinoid X receptor alpha (RXRA) genes and interindividual variations in immune responses after two doses of measles vaccine in 745 children. METHODS: Using a tag single nucleotide polymorphism (SNP) approach, we genotyped 745 healthy children for the 391 polymorphisms in vitamin A receptor and VDR genes. RESULTS: The RARB haplotype (rs6800566/rs6550976/rs9834818) was significantly associated with variations in both measles antibody (global, P=0.013) and cytokine secretion levels, such as interleukin (IL)-10 (global, P=0.006), interferon (IFN)-alpha (global, P=0.008), and tumor necrosis factor alpha (global, P=0.039) in the Caucasian subgroup. Specifically, the RARB haplotype, AAC, was associated with higher (t-statistic: 3.27, P=0.001) measles antibody levels. At the other end of the spectrum, haplotype GG for rs6550978/rs6777544 was associated with lower antibody levels (t-statistic: 2.32, P=0.020) in the Caucasian subgroup. In a sensitivity analysis, the RARB haplotype, CTGGGCAA, remained marginally significant (P<0.02) when the single SNP rs12630816 was included in the model for IL-10 secretion levels. A significant association was found between lower measles-specific IFN-gamma Enzyme-linked immunosorbent spot responses and haplotypes rs11102986/rs11103473/rs11103482/rs10776909/rs12004589/rs35780541/rs2266677/rs875 44 (global, P=0.004) and rs6537944/rs3118571 (global, P<0.001) in the RXRA gene for Caucasians. We also found associations between multiple RARB, VDR, and RXRA SNPs/haplotypes and measles-specific IL-2, IL-6, IL-10, IFN-alpha, IFN-gamma, IFNlambda-1, and TNF-alpha cytokine secretions. CONCLUSION: Our results suggest that specific allelic variations and haplotypes in the vitamin A receptor and VDR genes may influence adaptive immune responses to measles vaccine. PMID- 22082655 TI - Transplacental transfer of melamine. AB - OBJECTIVE: To characterize transplacental transfer of melamine and related mechanisms as well as toxicity using human placental perfusion and cultured cells. METHODS: Transfer and toxicity were analyzed in 4-h perfusions with 10 MUM or 1 mM melamine, or 10 MUM melamine with 10 nM cyanuric acid (CYA). Efflux transporters were studied in accumulation assay and toxicity in BeWo cells by MTT assay. RESULTS: Of added melamine 34-45% was transferred to fetal circulation and CYA made no difference. Histology, hCG production, and PLAP activity indicated functionality of placental tissue with no grave toxicity. Highest concentration of melamine used (2 mM) with CYA and long treatment time decreased viability of BeWo cells. Inhibitors of ABCB1, ABCG2, ABCC2 did not affect the accumulation of melamine in cells. CONCLUSION: Melamine goes through human term placenta with no contribution of efflux transporters. Toxicity of melamine is low in placental tissue and BeWo cells. PMID- 22082656 TI - Regarding "Therapeutic plasma exchange in amitriptyline intoxication: case report and review of the literature". PMID- 22082657 TI - Leukopheresis for profound hyperleukocytosis. AB - BACKGROUND: Leukocytoreduction by leukopheresis is recommended for hyperleukocytosis with leukemia, especially when accompanied by neurologic or respiratory symptoms. A single 1-1.5 blood volume leukocytopheresis is expected to reduce the leukocyte count by 30-60%. CASE REPORT: A 35 year old man presented with a 2 month history of hearing and visual loss and was found to have chronic myelogenous leukemia (CML) in chronic phase with 700,000 WBC/MUL. The blast count was 1%. The spleen was markedly enlarged. He was referred for leukocytopheresis and treatment of his leukemia. Despite the extremely high white cell count, he had a hematocrit of 24, platelets of 161,000/MUL, and normal lung, liver and renal function. RESULTS: A 15 L leukocytapheresis was performed with a Cobe Spectra with the removal of 1.86 L of bloody fluid with a hematocrit of 10% and a leukocrit of 28%. The blood white cell count decreased from 599,000 to 498,500/MUL, and the patient felt better. He was started on hydroxyuria and 8 days later his WBC was 7000/MUL. DISCUSSION: The patient's oncologists were initially concerned by the only 17% reduction in his white cell count. However, calculations based on his hematocrit and leukocrit in blood and waste bag suggested that he was 140% blood volume expanded by his leukemia and that the cytopheresis removed about half of the extra volume along with an additional 250 mL of leukocytes, about 35% of his pre-treatment WBC volume. The case and its implications for similar patients are discussed. PMID- 22082658 TI - Rescue of synaptic failure and alleviation of learning and memory impairments in a trisomic mouse model of down syndrome. AB - Down syndrome (DS) is caused by the triplication of ~240 protein-coding genes on chromosome 21 and is the most prevalent form of developmental disability. This condition results in abnormalities in many organ systems, as well as in intellectual retardation. Many previous efforts to understand brain dysfunction in DS have indicated that cognitive deficits are coincident with reduced synaptic plasticity and decreased neuronal proliferation. One therapeutic strategy for optimizing the microenvironment for neuronal proliferation and synaptic plasticity in the brain is the use of neurotrophins to restore the homeostasis of the brain biochemical milieu. Here, we show that peripheral administration of Peptide 6, an 11-mer corresponding to an active region of ciliary neurotrophic factor, amino acid residues 146 to 156, can inhibit learning and memory impairments in Ts65Dn mice, a trisomic mouse model of DS. Long-term treatment with Peptide 6 enhanced the pool of neural progenitor cells in the hippocampus and increased levels of synaptic proteins crucial for synaptic plasticity. These findings suggest a therapeutic potential of Peptide 6 in promoting functional neural integration into networks, thereby strengthening biologic substrates of memory processing. PMID- 22082659 TI - Promoter variants determine gamma-aminobutyric acid homeostasis-related gene transcription in human epileptic hippocampi. AB - The functional consequences of single nucleotide polymorphisms associated with episodic brain disorders such as epilepsy and depression are unclear. Allelic associations with generalized epilepsies have been reported for single nucleotide polymorphisms rs1883415 (ALDH5A1; succinic semialdehyde dehydrogenase) and rs4906902 (GABRB3; GABAA beta3), both of which are present in the 5' regulatory region of genes involved in gamma-aminobutyric acid (GABA) homeostasis. To address their allelic association with episodic brain disorders and allele specific impact on the transcriptional regulation of these genes in human brain tissue, DNA and messenger RNA (mRNA) isolated from hippocampi were obtained at epilepsy surgery of 146 pharmacoresistant mesial temporal lobe epilepsy (mTLE) patients and from 651 healthy controls. We found that the C allele of rs1883415 is accumulated to a greater extentin mTLE versus controls. By real-time quantitative reverse transcription-polymerase chain reaction analyses, individuals homozygous for the C allele showed higher ALDH5A1 mRNA expression. The rs4906902 G allele of the GABRB3 gene was overrepresented in mTLE patients with depression; individuals homozygous for the G allele showed reduced GABRB3 mRNA expression. Bioinformatic analyses suggest that rs1883415 and rs4906902 alter the DNA binding affinity of the transcription factors Egr-3 in ALDH5A1 and MEF-2 in GABRB3 promoters, respectively. Using in vitro luciferase transfection assays, we observed that, in both cases, the transcription factors regulate gene expression depending on the allelic variant in the same direction as in the human hippocampi. Our data suggest that distinct promoter variants may sensitize individuals for differential, potentially stimulus-induced alterations of GABA homeostasis-relevant gene expression. This might contribute to the episodic onset of symptoms and point to new targets for pharmacotherapies. PMID- 22082661 TI - Clusterin overexpression and its possible protective role in transthyretin deposition in familial amyloidotic polyneuropathy. AB - Extracellular chaperones such as clusterin may contribute to extracellular protein homeostasis in neurodegenerative disorders. It has been implicated in fibrillogenesis and extracellular misfolded protein clearance in Alzheimer disease. We investigated the localization and potential functions of clusterin in familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by extracellular deposition of mutant transthyretin (TTR) in the peripheral nervous system. We observed increased clusterin expression in human FAP nerves, in the dorsal root ganglia of mutant TTR transgenic mice with TTR deposition, and in human neuroblastoma cells incubated with oligomeric TTR. Clusterin colocalized with extracellular TTR aggregates in human FAP nerves and was detected in aggregates extracted from FAP tissues. Abolition of clusterin expression using small interfering RNA in a HEK293 cell line that secretes wild type TTR resulted in increased TTR aggregation in the medium, thus suggesting a protective role for clusterin in inhibition of TTR aggregation. However, under the conditions examined, toxicity of oligomeric TTR in neuroblastoma cells was unaltered by clusterin gene silencing. These data suggest that clusterin can influence TTR aggregation but may not modulate TTR aggregate toxicity or play a role in TTR clearance in FAP. Further studies will elucidate neuroprotective mechanisms conferred by clusterin in FAP and other neurodegenerative diseases. PMID- 22082660 TI - Morphologic and functional correlates of synaptic pathology in the cathepsin D knockout mouse model of congenital neuronal ceroid lipofuscinosis. AB - Mutations in the cathepsin D (CTSD) gene cause an aggressive neurodegenerative disease (congenital neuronal ceroid lipofuscinosis) that leads to early death. Recent evidence suggests that presynaptic abnormalities play a major role in the pathogenesis of CTSD deficiencies. To identify the early events that lead to synaptic alterations, we investigated synaptic ultrastructure and function in presymptomatic CTSD knockout (Ctsd) mice. Electron microscopy revealed that there were significantly greater numbers of readily releasable synaptic vesicles present in Ctsd mice than in wild-type control mice as early as postnatal day 16. The size of this synaptic vesicle pool continued to increase with disease progression in the hippocampus and thalamus of the Ctsd mice. Electrophysiology revealed a markedly decreased frequency of miniature excitatory postsynaptic currents (mEPSCs) with no effect on paired-pulse modulation of the evoked excitatory post synaptic potentials in the hippocampus of Ctsd mice. The reduced mEPSCs frequency was observed before the appearance of epilepsy or any morphologic sign of synaptic degeneration. Taken together, these data indicate that CTSD is required for normal synaptic function and that a failure in synaptic trafficking or recycling may bean early and important pathologic mechanism in Ctsd mice; these presynaptic abnormalities may initiate synaptic degeneration in advance of subsequent neuronal loss. PMID- 22082662 TI - Angiogenesis is regulated by angiopoietins during experimental autoimmune encephalomyelitis and is indirectly related to vascular permeability. AB - The regulation of angiogenesis was studied over the course of the animal model of multiple sclerosis, acute experimental autoimmune encephalomyelitis (EAE) in mice using immunohistochemistry. During EAE, angiogenesis peaked 21 days after disease induction, with significant increases in gray matter and adjacent to the leptomeninges. Angiogenesis correlated with clinical and pathologic scores. Spinal cord expression of angiopoietin 1 (Ang-1) by neurons and glia was reduced at Day 14, but expression by inflammatory cells restored earlier levels at Day 21. Angiopoietin 2 expression increased markedly at Day 21 and was mostly associated with inflammatory cells. Levels of the angiopoietin receptor Tie-2 were reduced at Day 14, but recovered by day D21. Double labeling demonstrated Ang-1 expression on infiltrating CD3-positive T cells; Ang-2 was expressed by monocytes/macrophages. During EAE, the expression of vascular endothelial growth factor peaked at Day 14 and began to decrease by Day 21. Double labeling showed expression of Tie-2 and vascular endothelial growth factor receptor 2 but not Ang 2 in blood vessels at Day 21. Vascular permeability increased early in EAE, but was reduced by Day 21. Although individual values did not correlate with angiogenesis, the volume of permeable tissue showed a weak positive correlation with angiogenesis. These temporal changes in angiogenic factors suggest an integral role during EAE-related angiogenesis. PMID- 22082663 TI - Developmental aspects of the intracerebral microvasculature and perivascular spaces: insights into brain response to late-life diseases. AB - The development of the microvasculature of the human cerebral cortex offers insight into the response of the cerebral cortex to later-life brain injury. We describe the 3 basic and distinct components of the developmental anatomy of the cerebral cortical microvascular system. The first compartment is meningeal and, therefore, extracerebral. In addition to the major venous sinuses, arachnoidal arteries, and veins, the pial anastomotic capillary plexus that covers the surface of the developing and adult cerebral cortex represents the source of thepenetrating vessels that become the second component, the intracerebral extrinsic microvascular compartment. During embryogenesis, sprouting vascular elements from pial capillaries pierce the brain's external glial limiting membrane and penetrate the cortex. These vessels, which eventually differentiate into arterioles and venules, are separated from the cortical tissue by the extravascular Virchow-Robin compartment (V-RC) formed between the internal vascular and the external glial basal laminae. The V-RC remains open to the meningeal interstitial spaces and outside the blood-brain barrier (BBB) and acts asa prelymphatic drainage system for removal of substances that cannot be transported into the blood or catabolized intracellularly. The third element is the dense intracerebralintrinsic microvascular compartment. Intracerebral capillary vessels sprout from the perforating vessels, penetrate through the Virchow-Robin glial membrane, and enter the neuropil. Intracerebral capillaries lack smooth muscle and a V-RC and consist only of endothelial cells separated from the intracerebral space by a basal lamina. Their role as the physiological BBB is the exchange of oxygen, glucose, and small molecules. This developmental perspective highlights 3 principles: (a) the V-RC is intimately related to the cortical penetrating arterioles and venules and represents an inefficient protolymphatic system that lacks the anatomic and physiological constituents found in lymphatic beds elsewhere in the body; (b)the anatomic contiguity of the V-RC and the penetrating vascular compartment (arterioles and venules) implies that the pathology in 1 compartment could lead to dysfunction in the others; and (c) the anatomic localization of the immunologic BBB at the level of the penetrating venules might impose constraints on immunologically mediated transport involving the V-RC. PMID- 22082664 TI - Changes in brain beta-amyloid deposition and aquaporin 4 levels in response to altered agrin expression in mice. AB - Conditions that compromise the blood-brain barrier (BBB) have been increasingly implicated in the pathogenesis of Alzheimer disease (AD). AGRIN is a heparan sulfate proteoglycan found abundantly in basement membranes of the cerebral vasculature, where it has been proposed to serve a functional role in the BBB. Furthermore, AGRIN is the major heparan sulfate proteoglycan associated with amyloid plaques in AD brains. To examine the relationship of AGRIN, the BBB, and AD-related pathologies, we generated mice in which the Agrn gene was deleted from either endothelial cells or neurons using gene targeting or was overexpressed using a genomic transgene construct. These mice were combined with a transgenic model of AD that over expresses disease-associated forms of amyloid precursor protein and presenilin 1. In mice lacking endothelial cell expression of Agrn, the BBB remained intact but aquaporin 4 levels were reduced, indicating that the loss of AGRIN affects BBB-associated components. This change in Agrn resulted in an increase in beta-amyloid (Abeta) in the brain. Conversely, overexpression of Agrn decreased Abeta deposition, whereas elimination of Agrn from neurons did not change Abeta levels. These results indicate that AGRIN is important for maintaining BBB composition and that changes in Agrn expression (particularly vessel-associated AGRIN) influence Abeta homeostasis in mouse models of AD. PMID- 22082665 TI - On the occurrence of hypomyelination in a transgenic mouse model: a consequence of the myelin basic protein promoter? AB - Central nervous system hypomyelination is a feature common to a number of transgenic (Tg) mouse lines that express a variety of unrelated exogenous (i.e. non-central nervous system) transgenes. In this report, we document hypomyelination structurally by immunocytochemistry and functionally in the Tg line MBP-JE, which over expresses the chemokine CCL2 (MCP-1) within oligodendrocytes targeted by a myelin basic protein (MBP) promoter. Analysis of hypomyelinated optic nerves of Tg mice revealed progressive decrease in oligodendrocyte numbers with age (p < 0.01). Although molecular mechanisms underlying hypomyelination in this and other Tg models remain largely unknown, we present preliminary findings on oligodendrocyte progenitor cell (OPC) cultures in which, although OPC expressed CCR2, the receptor for CCL2, treatment with CCL2 had no significant effect on OPC proliferation, differentiation, or apoptosis. We suggest that hypomyelination in the MBP-JE model might not be due to CCL2 expression but rather the result of transcriptional dysfunction related to random insertion of the MBP promoter that disrupts myelinogenesis and leads to oligodendrocyte demise. Because an MBP promoter is a common denominator in most Tg lines displaying hypomyelination, we hypothesize that use of myelin gene sequences in the regulator region of Tg constructs might underlie this perturbation of myelination in such models. PMID- 22082666 TI - Strigolactone analogues and mimics derived from phthalimide, saccharine, p tolylmalondialdehyde, benzoic and salicylic acid as scaffolds. AB - A series of new strigolactone (SL) analogues is derived from simple and cheap starting materials. These SL analogues are designed using a working model. The first analogue is a modified Nijmegen-1, the second contains saccharin as substituent (bio-isosteric replacement of a carbonyl in Nijmegen-1 by a sulfonyl group) and the third one is derived from p-tolylmalondialdehyde. These new SL analogues are appreciably to highly active as germination stimulants of seeds of Striga hermonthica and Orobanche cernua. The SL analogue derived from saccharin is the most active one. A serendipitous and most rewarding finding is that the compound obtained by a direct coupling of saccharin with the chlorobutenolide exhibits a high germination activity especially towards O. cernua seeds. Two other SL mimics are obtained from benzoic and salicylic aid by a direct coupling reaction with chlorobutenolide, both of them are very active germinating agents. These SL mimics represent a new type of germination stimulants. A tentative molecular mechanism for the mode of action of these SL mimics has been proposed. PMID- 22082667 TI - Time-dependent botulinum neurotoxin serotype A metalloprotease inhibitors. AB - Botulinum neurotoxins (BoNTs) are the most lethal of biological substances, and are categorized as class A biothreat agents by the Centers for Disease Control and Prevention. There are currently no drugs to treat the deadly flaccid paralysis resulting from BoNT intoxication. Among the seven BoNT serotypes, the development of therapeutics to counter BoNT/A is a priority (due to its long half life in the neuronal cytosol and its ease of production). In this regard, the BoNT/A enzyme light chain (LC) component, a zinc metalloprotease responsible for the intracellular cleavage of synaptosomal-associated protein of 25 kDa, is a desirable target for developing post-BoNT/A intoxication rescue therapeutics. In an earlier study, we reported the high throughput screening of a library containing 70,000 compounds, and uncovered a novel class of benzimidazole acrylonitrile-based BoNT/A LC inhibitors. Herein, we present both structure activity relationships and a proposed mechanism of action for this novel inhibitor chemotype. PMID- 22082668 TI - Triglycerides are independently associated with albuminuria in Taiwanese Type 2 diabetic patients. AB - BACKGROUND: Lipid abnormalities in albuminuria in patients with Type 2 diabetes differ by race. AIM: To perform a biochemical investigation of association between dyslipidemia and albuminuria in Type 2 diabetes in Taiwan. MATERIALS/ SUBJECTS AND METHODS: We recruited a total of 2349 Chinese patients with Type 2 diabetes from two medical centers in Taiwan over a 1-yr period. Patients were categorized into those with normoalbuminuria, microalbuminuria, and macroalbuminuria defined as albumin-to-creatinine ratio of <30, 30- 299, and >=300 MUg/mg. We then investigated the significance of the clinical and biochemical parameters and risk of albuminuria. RESULTS: We found significant differences in total cholesterol (TC) between those with normoalbuminuria and micro/ macroalbuminuria, no significant difference in LDL cholesterol (LDL-C) among the 3 subgroups, a significant difference in HDL cholesterol (HDL-C) between those with normoalbuminuria and macroalbuminuria, and significant increases in triglyceride (TG) paralleling increases in albuminuria. TG was found by logistic regression to be significantly associated with micro/macroalbuminuria in our unadjusted model [odds ratio (OR) = 1.859 (1.596~2.165)], and remained significant after adjusting for various confounders [OR = 1.415 (1.123~1.784)]. Increases in albuminuria paralleled quartile increases in serum TG (p<0.001). CONCLUSIONS: We conclude that TG increases significantly throughout the 3 stages of albuminuria in Taiwanese Type 2 diabetic patients, but TC, HDL-C, and LDL-C do not. PMID- 22082671 TI - Introductory perspective. PMID- 22082670 TI - Is the association between ACE genes and blood pressure mediated by postnatal growth during the first 3 years? AB - Unlike the defined role of angiotensin-converting enzyme (ACE) gene in adult hypertension, ACE gene did not show direct influence on childhood blood pressure (BP), rather, seemed to be related to childhood growth with age-dependent characteristics. Thus, we examined intermediate effects of postnatal growth between the ACE polymorphisms and BP. We analyzed data from 257 children born in 2001-04 at Ewha Womans University Hospital in Seoul, Korea, and followed them up until 3 years of age. Children with excessive adiposity had higher BP, as rapid growers did to no-change and decelerated growers. The ACE II genotype was associated with greater growth acceleration than the DD genotype (II: 46.8% vs. DD: 23.9%), and with a higher BP. The interactions between ACE genotype and adiposity at age 3 were significant on the BP levels. The highest BP increase with the same degree of adiposity was observed in those with the II genotype [beta (SE) for BMI: 1.9 (0.9), p=0.04]; particularly, only rapid grown II carriers demonstrated statistical significance on this linear association. These results suggested that ACE polymorphisms and BP association are mediated by postnatal growth. Further studies are required to determine the age-specific ACE genetic effects and its undefined biological mechanism. PMID- 22082669 TI - Statistical mechanics and molecular dynamics in evaluating thermodynamic properties of biomolecular recognition. AB - Molecular recognition plays a central role in biochemical processes. Although well studied, understanding the mechanisms of recognition is inherently difficult due to the range of potential interactions, the molecular rearrangement associated with binding, and the time and length scales involved. Computational methods have the potential for not only complementing experiments that have been performed, but also in guiding future ones through their predictive abilities. In this review, we discuss how molecular dynamics (MD) simulations may be used in advancing our understanding of the thermodynamics that drive biomolecular recognition. We begin with a brief review of the statistical mechanics that form a basis for these methods. This is followed by a description of some of the most commonly used methods: thermodynamic pathways employing alchemical transformations and potential of mean force calculations, along with end-point calculations for free energy differences, and harmonic and quasi-harmonic analysis for entropic calculations. Finally, a few of the fundamental findings that have resulted from these methods are discussed, such as the role of configurational entropy and solvent in intermolecular interactions, along with selected results of the model system T4 lysozyme to illustrate potential and current limitations of these methods. PMID- 22082673 TI - Atrial fibrillation catheter ablation versus surgical ablation treatment (FAST): a 2-center randomized clinical trial. AB - BACKGROUND: Catheter ablation (CA) and minimally invasive surgical ablation (SA) have become accepted therapy for antiarrhythmic drug-refractory atrial fibrillation. This study describes the first randomized clinical trial comparing their efficacy and safety during a 12-month follow-up. METHODS AND RESULTS: One hundred twenty-four patients with antiarrhythmic drug-refractory atrial fibrillation with left atrial dilatation and hypertension (42 patients, 33%) or failed prior CA (82 patients, 67%) were randomized to CA (63 patients) or SA (61 patients). CA consisted of linear antral pulmonary vein isolation and optional additional lines. SA consisted of bipolar radiofrequency isolation of the bilateral pulmonary vein, ganglionated plexi ablation, and left atrial appendage excision with optional additional lines. Follow-up at 6 and 12 months was performed by ECG and 7-day Holter recording. The primary end point, freedom from left atrial arrhythmia >30 seconds without antiarrhythmic drugs after 12 months, was 36.5% for CA and 65.6% for SA (P=0.0022). There was no difference in effect for subgroups, which was consistent at both sites. The primary safety end point of significant adverse events during the 12-month follow-up was significantly higher for SA than for CA (n=21 [34.4%] versus n=10 [15.9%]; P=0.027), driven mainly by procedural complications such as pneumothorax, major bleeding, and the need for pacemaker. In the CA group, 1 patient died at 1 month of subarachnoid hemorrhage. CONCLUSION: In atrial fibrillation patients with dilated left atrium and hypertension or failed prior atrial fibrillation CA, SA is superior to CA in achieving freedom from left atrial arrhythmias after 12 months of follow-up, although the procedural adverse event rate is significantly higher for SA than for CA. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00662701. PMID- 22082676 TI - Referral, enrollment, and delivery of cardiac rehabilitation/secondary prevention programs at clinical centers and beyond: a presidential advisory from the American Heart Association. PMID- 22082674 TI - Pak1 as a novel therapeutic target for antihypertrophic treatment in the heart. AB - BACKGROUND: Stress-induced hypertrophic remodeling is a critical pathogenetic process leading to heart failure. Although many signal transduction cascades are demonstrated as important regulators to facilitate the induction of cardiac hypertrophy, the signaling pathways for suppressing hypertrophic remodeling remain largely unexplored. In this study, we identified p21-activated kinase 1 (Pak1) as a novel signaling regulator that antagonizes cardiac hypertrophy. METHODS AND RESULTS: Hypertrophic stress applied to primary neonatal rat cardiomyocytes (NRCMs) or murine hearts caused the activation of Pak1. Analysis of NRCMs expressing constitutively active Pak1 or in which Pak1 was silenced disclosed that Pak1 played an antihypertrophic role. To investigate the in vivo role of Pak1 in the heart, we generated mice with a cardiomyocyte-specific deletion of Pak1 (Pak1(cko)). When subjected to 2 weeks of pressure overload, Pak1(cko) mice developed greater cardiac hypertrophy with attendant blunting of JNK activation compared with controls, and these knockout mice underwent the transition into heart failure when prolonged stress was applied. Chronic angiotensin II infusion also caused increased cardiac hypertrophy in Pak1(cko) mice. Moreover, we discovered that the Pak1 activator FTY720, a sphingosine-like analog, was able to prevent pressure overload-induced hypertrophy in wild-type mice without compromising their cardiac functions. Meanwhile, FTY720 failed to exert such an effect on Pak1(cko) mice, suggesting that the antihypertrophic effect of FTY720 likely acts through Pak1 activation. CONCLUSIONS: These results, for the first time, establish Pak1 as a novel antihypertrophic regulator and suggest that it may be a potential therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID- 22082675 TI - A critical role for the protein apoptosis repressor with caspase recruitment domain in hypoxia-induced pulmonary hypertension. AB - BACKGROUND: Pulmonary hypertension (PH) is a lethal syndrome associated with the pathogenic remodeling of the pulmonary vasculature and the emergence of apoptosis resistant cells. Apoptosis repressor with caspase recruitment domain (ARC) is an inhibitor of multiple forms of cell death known to be abundantly expressed in striated muscle. We show for the first time that ARC is expressed in arterial smooth muscle cells of the pulmonary vasculature and is markedly upregulated in several experimental models of PH. In this study, we test the hypothesis that ARC expression is essential for the development of chronic hypoxia-induced PH. METHODS AND RESULTS: Experiments in which cells or mice were rendered ARC deficient revealed that ARC not only protected pulmonary arterial smooth muscle cells from hypoxia-induced death, but also facilitated growth factor-induced proliferation and hypertrophy and hypoxia-induced downregulation of selective voltage-gated potassium channels, the latter a hallmark of the syndrome in humans. Moreover, ARC-deficient mice exhibited diminished vascular remodeling, increased apoptosis, and decreased proliferation in response to chronic hypoxia, resulting in marked protection from PH in vivo. Patients with PH have significantly increased ARC expression not only in remodeled vessels but also in the lumen-occluding lesions associated with severe disease. CONCLUSIONS: These data show that ARC, previously unlinked to pulmonary hypertension, is a critical determinant of vascular remodeling in this syndrome. PMID- 22082677 TI - Heparin elevates circulating soluble fms-like tyrosine kinase-1 immunoreactivity in pregnant women receiving anticoagulation therapy. AB - BACKGROUND: Alterations in circulating levels of pro- and antiangiogenic factors have been associated with adverse pregnancy outcomes. Heparin is routinely administered to pregnant women, but without clear knowledge of its impact on these factors. METHODS AND RESULTS: We conducted a longitudinal study of 42 pregnant women. Twenty-one women received prophylactic heparin anticoagulation, and 21 healthy pregnant women served as controls. Compared with gestational age matched controls, heparin treatment was associated with increased circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1) in the third trimester (P<0.05), in the absence of preeclampsia, placental abruption, or fetal growth restriction. Heparin had no effect on circulating levels of vascular endothelial growth factor, placenta growth factor, or soluble endoglin as assessed by ELISA. In vitro, low-molecular weight and unfractionated heparins stimulated sFlt-1 release from placental villous explants, in a dose- and time-dependent manner. This effect was not due to placental apoptosis, necrosis, alteration in protein secretion, or increased transcription. Western blot analysis demonstrated that heparin induced shedding of the N-terminus of Flt-1 both in vivo and in vitro as indicated by a predominant band of 100-112 kDa. By using an in vitro angiogenesis assay, we demonstrated that serum of heparin-treated cases inhibited both basal and vascular endothelial growth factor-induced capillary-like tube formation. CONCLUSIONS: Heparin likely increases the maternal sFlt-1 through shedding of the extracellular domain of Flt-1 receptor. Our results imply that upregulation of circulating sFlt-1 immunoreactivity in pregnancy is not always associated with adverse outcomes, and that heparin's protective effects, if any, cannot be explained by promotion of angiogenesis. PMID- 22082678 TI - Pathogenic cycle between the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine and the leukocyte-derived hemoprotein myeloperoxidase. AB - BACKGROUND: The nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and the leukocyte-derived hemoprotein myeloperoxidase (MPO) are associated with cardiovascular diseases. Activation of monocytes and polymorphonuclear neutrophils (PMNs) with concomitant release of MPO is regulated in a nitric oxide dependent fashion. The aim of the study was to investigate a potential 2-way interaction between ADMA and MPO. METHODS AND RESULTS: Ex vivo, ADMA uptake by isolated human PMNs, the principal source of MPO in humans, significantly impaired nitric oxide synthase activity determined by gas chromatography-mass spectrometry. In humans, short-term ADMA infusion (0.0125 mg . kg(-1) . min(-1)) significantly increased MPO plasma concentrations. Functionally, PMN exposure to ADMA enhanced leukocyte adhesion to endothelial cells, augmented NADPH oxidase activity, and stimulated PMN degranulation, resulting in release of MPO. In vivo, a 28-day ADMA infusion (250 MUmol . kg(-1) . d(-1)) in C57Bl/6 mice significantly increased plasma MPO concentrations, whereas this ADMA effect on MPO was attenuated by human dimethylarginine dimethylaminohydrolase1 (hDDAH1) overexpression. Moreover, the MPO-derived reactive molecule hypochlorous acid impaired recombinant hDDAH1 activity in vitro. In MPO(-/-) mice, the lipopolysaccharide-induced increase in systemic ADMA concentrations was abrogated. CONCLUSIONS: ADMA profoundly impairs nitric oxide synthesis of PMNs, resulting in increased PMN adhesion to endothelial cells, superoxide generation, and release of MPO. In addition, MPO impairs DDAH1 activity. Our data reveal an ADMA-induced cycle of PMN activation, enhanced MPO release, and subsequent impairment of DDAH1 activity. These findings not only highlight so far unrecognized cytokine-like properties of ADMA but also identify MPO as a regulatory switch for ADMA bioavailability under inflammatory conditions. PMID- 22082679 TI - Absence of SOCS3 in the cardiomyocyte increases mortality in a gp130-dependent manner accompanied by contractile dysfunction and ventricular arrhythmias. AB - BACKGROUND: Suppressor of cytokine signaling-3 (SOCS3) is a key negative-feedback regulator of the gp130 receptor that provides crucial signaling for cardiac hypertrophy and survival; however, an in vivo role of SOCS3 regulation on cardiac gp130 signaling remains obscure. METHODS AND RESULTS: We generated cardiac specific SOCS3 knockout (SOCS3 cKO) mice. These mice showed increased activation of gp130 downstream signaling targets (STAT3, ERK1/2, AKT, and p38) from 15 weeks of age and developed cardiac dysfunction from approximately 25 weeks of age with signs of heart failure. Surprisingly, SOCS3 cKO failing hearts had minimal histological abnormalities with intact myofibril ultrastructure. In addition, Ca(2+) transients were significantly increased in SOCS3 cKO failing hearts compared with wild-type hearts. We also found that Ser23/24 residues of troponin I were hypophosphorylated in SOCS3 cKO hearts before the manifestation of cardiac dysfunction. These data suggested the presence of abnormalities in myofilament Ca(2+) sensitivity in SOCS3 cKO mice. In addition to the contractile dysfunction, we found various ventricular arrhythmias in SOCS3 cKO nonfailing hearts accompanied by a sarcoplasmic reticulum Ca(2+) overload. To determine the contribution of gp130 signaling to the cardiac phenotype that occurs with SOCS3 deficiency, we generated cardiac-specific gp130 and SOCS3 double KO mice. Double KO mice lived significantly longer and had different histological abnormalities when compared with SOCS3 cKO mice, thus demonstrating the importance of gp130 signaling in the SOCS3 cKO cardiac phenotype. CONCLUSIONS: Our results demonstrate an important role of SOCS3 regulation on cardiac gp130 signaling in the pathogenesis of contractile dysfunction and ventricular arrhythmias. PMID- 22082680 TI - A key role for matrix metalloproteinases and neutral sphingomyelinase-2 in transplant vasculopathy triggered by anti-HLA antibody. AB - BACKGROUND: Outcomes for organ transplantation are constantly improving because of advances in organ preservation, surgical techniques, immune clinical monitoring, and immunosuppressive treatment preventing acute transplant rejection. However, chronic rejection including transplant vasculopathy still limits long-term patient survival. Transplant vasculopathy is characterized by progressive neointimal hyperplasia leading to arterial stenosis and ischemic failure of the allograft. This work sought to decipher the manner in which the humoral immune response, mimicked by W6/32 anti-HLA antibody, contributes to transplant vasculopathy. METHODS AND RESULTS: Studies were performed in vitro on cultured human smooth muscle cells, ex vivo on human arterial segments, and in vivo in a model consisting of human arterial segments grafted into severe combined immunodeficiency/beige mice injected weekly with anti-HLA antibodies. We report that anti-HLA antibodies are mitogenic for smooth muscle cells through a signaling mechanism implicating matrix metalloproteinases (MMPs) (membrane type 1 MMP and MMP2) and neutral sphingomyelinase-2. This mitogenic signaling and subsequent DNA synthesis are blocked in smooth muscle cells silenced for MMP2 or for neutral sphingomyelinase-2 by small interfering RNAs, in smooth muscle cells transfected with a vector coding for a dominant-negative form of membrane type 1 MMP, and after treatment by pharmacological inhibitors of MMPs (Ro28-2653) or neutral sphingomyelinase-2 (GW4869). In vivo, Ro28-2653 and GW4869 reduced the intimal thickening induced by anti-HLA antibodies in human mesenteric arteries grafted into severe combined immunodeficiency/beige mice. CONCLUSIONS: These data highlight a crucial role for MMP2 and neutral sphingomyelinase-2 in vasculopathy triggered by a humoral immune response and open new perspectives for preventing transplant vasculopathy with the use of MMP and neutral sphingomyelinase inhibitors, in addition to conventional immunosuppression. PMID- 22082682 TI - Sympathetic nerve blocks, pragmatic trials, and responder analysis. PMID- 22082681 TI - Predictive value of the high-sensitivity troponin T assay and the simplified Pulmonary Embolism Severity Index in hemodynamically stable patients with acute pulmonary embolism: a prospective validation study. AB - BACKGROUND: The new, high-sensitivity troponin T (hsTnT) assay may improve risk stratification of normotensive patients with acute pulmonary embolism (PE). We externally validated the prognostic value of hsTnT, and of the simplified Pulmonary Embolism Severity Index (sPESI), in a large multicenter cohort. METHODS AND RESULTS: We prospectively examined 526 normotensive patients with acute PE; of those, 31 (5.9%) had an adverse 30-day outcome. The predefined hsTnT cutoff value of 14 pg/mL was associated with a high prognostic sensitivity and negative predictive value, comparable to those of the sPESI. Both hsTnT >=14 pg/mL (OR, 4.97 [95% CI, 1.71-14.43]; P=0.003) and sPESI >=1 point(s) (OR, 9.51 [2.24 40.29]; P=0.002) emerged, besides renal insufficiency (OR, 2.97 [1.42-6.22]; P=0.004), as predictors of early death or complications; in a multivariable model, they remained independent predictors of outcome (P=0.044 and 0.012, respectively). A total of 127 patients (24.1%) were identified as low risk by a sPESI of 0 and hsTnT <14 pg/mL; none of them had an adverse 30-day outcome. During 6-month follow-up, 52 patients (9.9%) died. Kaplan-Meier analysis illustrated that patients with hsTnT >=14 pg/mL (P=0.001) and those with sPESI >=1 (P<0.001) had a decreased probability of 6-month survival. Patients with sPESI of 0 and hsTnT <14 pg/mL at baseline had a 42% reduction in the risk of dying (hazard ratio, 0.58 [0.01-0.42]; P=0.005). CONCLUSIONS: The hsTnT assay and the sPESI improve risk stratification of acute PE. Combination of both modalities may yield additive prognostic information and particularly identify possible candidates for out-of-hospital treatment. PMID- 22082683 TI - Selective 5-HT(1A)-R-agonist repinotan prevents remifentanil-induced ventilatory depression and prolongs antinociception. AB - BACKGROUND: 5-HT(1A)-R-agonist repinotan was shown to counteract a morphine induced ventilatory depression but had pronociceptive effects at small doses (0.2 MUg/kg). It remained to be clarified (1) whether a moderate dose of repinotan, sufficient to stimulate spontaneous breathing, impairs antinociception if plasma concentration decreases over time, and if (2) moderate doses prevent ventilatory depression if given before the opioid. METHODS: A dose-response curve of the repinotan effects on spontaneous minute ventilation during continuous remifentanil infusion in anesthetized rats was established to identify moderate doses: (1) tail-flick reflex latencies to assess nociception were recorded until 60 min after cessation of a continuous remifentanil infusion with or without a concomitant moderate repinotan dose (10 MUg/kg), and (2) remifentanil boluses (2.5 MUg/kg) were given after repinotan (10 and 20 MUg/kg). RESULTS: (1) Remifentanil-induced antinociception lasted only 5 min after infusion was stopped (tail-flick reflex latencies; median [interquartile range], 97 [54-100]% of maximum possible effect; P = 0.034), but was extended by repinotan (10 MUg/kg) to 30 min (tail-flick reflex latencies, 100 [75-100]% of maximum possible effect; P = 0.031). Repinotan (10 MUg/kg) alone did not have any significant antinociceptive effect. (2) The ventilatory depression by remifentanil boluses (2.5 MUg/kg; minute ventilation, -65 [-81 to -56]%; P = 0.031, n = 5) was blunted by repinotan (20 MUg/kg; minute ventilation, -24 [-53 to 13]%; P = 0.313, compared with the pretreatment level). CONCLUSIONS: Repinotan prevented remifentanil-induced ventilatory depression in spontaneously breathing, anesthetized rats. Although repinotan did not depress nociception itself, it prolonged the profound antinociception after discontinuation of remifentanil infusion. PMID- 22082685 TI - Reliability and component structure of the modified Daily Symptom Report (DSR 20). AB - OBJECTIVES: The purpose of the present study was to modify Freeman et al.'s (1996) Daily Symptom Report (DSR) for premenstrual syndrome (PMS) by adding items depicting aggressive and impulsive symptoms, to explore the component structure of this revised measure (DSR-20) in a sample of PMS sufferers, and to compare their scores with those from controls during the follicular and luteal cycle phases. METHODS: The DSR-20 was administered to 140 PMS sufferers who were seeking treatment for PMS and 54 controls who considered themselves to be free from premenstrual complaints daily for three menstrual cycles. RESULTS: Cronbach's alpha was 0.95 for the luteal DSR-20 scores of the PMS sufferers, indicating very high internal consistency of the 20 items. Exploratory Principal Components Analysis (PCA) of the luteal ratings of the PMS sufferers identified two components with high internal consistency (>0.90), describing psychological and physical premenstrual symptoms. PMS sufferers scored significantly higher than the controls on each of these components during the luteal, but not follicular, phase. CONCLUSIONS: The DSR-20 total scale score is an internally consistent global measure of the intensity of PMS. The division of PMS symptoms into psychological and physical components, both of which significantly differentiated PMS sufferers from controls during the luteal phase, sheds further light on the description of PMS and provides a clinically relevant and practical means by which to summarise and interpret daily symptom ratings, necessary for the identification and investigation of the syndrome. PMID- 22082686 TI - Early predictors of short term neurodevelopmental outcome in asphyxiated cooled infants. A combined brain amplitude integrated electroencephalography and near infrared spectroscopy study. AB - BACKGROUND: Brain Cooling (BC) represents the elective treatment in asphyxiated newborns. Amplitude Integrated Electroencephalography (aEEG) and Near Infrared Spectroscopy (NIRS) monitoring may help to evaluate changes in cerebral electrical activity and cerebral hemodynamics during hypothermia. OBJECTIVES: To evaluate the prognostic value of aEEG time course and NIRS data in asphyxiated cooled infants. METHODS: Twelve term neonates admitted to our NICU with moderate severe Hypoxic-Ischemic Encephalopathy (HIE) underwent selective BC. aEEG and NIRS monitoring were started as soon as possible and maintained during the whole hypothermic treatment. Follow-up was scheduled at regular intervals; adverse outcome was defined as death, cerebral palsy (CP) or global quotient <88.7 at Griffiths' Scale. RESULTS: 2/12 Infants died, 2 developed CP, 1 was normal at 6 months of age and then lost at follow-up and 7 showed a normal outcome at least at 1 year of age. The aEEG background pattern at 24 h of life was abnormal in 10 newborns; only 4 of them developed an adverse outcome, whereas the 2 infants with a normal aEEG developed normally. In infants with adverse outcome NIRS showed a higher Tissue Oxygenation Index (TOI) than those with normal outcome (80.0+/ 10.5% vs 66.9+/-7.0%, p=0.057; 79.7+/-9.4% vs 67.1+/-7.9%, p=0.034; 80.2+/-8.8% vs 71.6+/-5.9%, p=0.069 at 6, 12 and 24 h of life, respectively). CONCLUSIONS: The aEEG background pattern at 24h of life loses its positive predictive value after BC implementation; TOI could be useful to predict early on infants that may benefit from other innovative therapies. PMID- 22082687 TI - Unusual Doppler trace in mitral stenosis: prominent isovolumic relaxation flow. PMID- 22082672 TI - Efficacy and safety of celivarone, with amiodarone as calibrator, in patients with an implantable cardioverter-defibrillator for prevention of implantable cardioverter-defibrillator interventions or death: the ALPHEE study. AB - BACKGROUND: Celivarone is a new antiarrhythmic agent developed for the treatment of ventricular arrhythmias. This study investigated the efficacy and safety of celivarone in preventing implantable cardioverter-defibrillator (ICD) interventions or death. METHODS AND RESULTS: Celivarone (50, 100, or 300 mg/d) was assessed compared with placebo in this randomized, double-blind, placebo controlled, parallel-group study. Amiodarone (200 mg/d after loading dose of 600 mg/d for 10 days) was used as a calibrator. A total of 486 patients with a left ventricular ejection fraction <=40% and at least 1 ICD intervention for ventricular tachycardia or ventricular fibrillation in the previous month or ICD implantation in the previous month for documented ventricular tachycardia/ventricular fibrillation were randomized. Median treatment duration was 9 months. The primary efficacy end point was occurrence of ventricular tachycardia/ventricular fibrillation-triggered ICD interventions (shocks or antitachycardia pacing) or sudden death. The proportion of patients experiencing an appropriate ICD intervention or sudden death was 61.5% in the placebo group; 67.0%, 58.8%, and 54.9% in the celivarone 50-, 100-, and 300-mg groups, respectively; and 45.3% in the amiodarone group. Hazard ratios versus placebo for the primary end point ranged from 0.860 for celivarone 300 mg to 1.199 for celivarone 50 mg. None of the comparisons versus placebo were statistically significant. Celivarone had an acceptable safety profile. CONCLUSIONS: Celivarone was not effective for the prevention of ICD interventions or sudden death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00993382. PMID- 22082684 TI - Relationship between testosterone deficiency and cardiovascular risk and mortality in adult men. AB - Classic male hypogonadism is associated with known adverse effects including decreased libido, erectile dysfunction, osteoporosis, and changes in body composition. Recently, we have come to appreciate that reduction in serum testosterone (T) levels resulting from aging or chronic disease or androgen deprivation therapy (ADT) have consequences similar to those seen in classic male hypogonadism which include increased fat mass, decreased lean body mass, decreased muscle strength, and sexual dysfunction. These data suggest that low T levels may represent a newly recognized cardiometabolic risk factor. Therefore, we carried out a careful review of the literature, focusing on major turning points of research and studies which gave more important and controversial contribution to the cardiovascular role of T. Observational studies and clinical trials investigating the relationship between T levels and cardiovascular disease and mortality were identified byMedline search. The results were synthesized, tabulated, and interpreted. The aim of this review is to discuss the association between low T levels and adverse metabolic profile such as insulin resistance, metabolic syndrome, and diabetes. We will also investigate the potential mechanisms by which male hypogonadism, especially age related or induced by ADT, may increase cardio-metabolic risk. Finally we will detail the emerging relationship between low T and mortality in men addressing also the reverse hypothesis that low T has a protective role by turning off T-dependent functions. PMID- 22082688 TI - Myocardial perfusion scintigraphy: technical innovations and evolving clinical applications. PMID- 22082689 TI - Cardiac MRI of Lyme disease myocarditis. PMID- 22082690 TI - Pulmonary hypertension due to a large acquired systemic arteriovenous fistula. PMID- 22082691 TI - Electron tomography of cells. AB - The electron microscope has contributed deep insights into biological structure since its invention nearly 80 years ago. Advances in instrumentation and methodology in recent decades have now enabled electron tomography to become the highest resolution three-dimensional (3D) imaging technique available for unique objects such as cells. Cells can be imaged either plastic-embedded or frozen hydrated. Then the series of projection images are aligned and back-projected to generate a 3D reconstruction or 'tomogram'. Here, we review how electron tomography has begun to reveal the molecular organization of cells and how the existing and upcoming technologies promise even greater insights into structural cell biology. PMID- 22082692 TI - Spinal cord tumor versus transverse myelitis. AB - BACKGROUND CONTEXT: Longitudinally extensive transverse myelitis (LETM) is one of the defining features of neuromyelitis optica (NMO). Despite the well-established criteria, clinical and paraclinical features, the disease is often misdiagnosed and erroneously treated. PURPOSE: We report on a case of LETM in a patient with spatially limited NMO spectrum disorder that was misdiagnosed as spinal cord tumor and underwent spinal cord biopsy. STUDY DESIGN: A 43-year-old female patient is described. METHODS: The patient developed spastic tetraparesis over 1 week. Spinal cord magnetic resonance imaging (MRI) revealed LETM, and she was treated with steroids and recovered. Nine months later, her condition worsened and repeat spinal cord MRI was interpreted as a large intramedullary tumor in the cervical region with irregular postcontrast enhancement. Biopsy revealed demyelination. Cerebrospinal fluid (CSF) analysis revealed positive oligoclonal IgG bands, and serum was positive for NMO-IgG antibody. RESULTS: The patient was diagnosed with spatially limited NMO spectrum disorder, treated with plasma exchange, high-dose corticosteroids, and cyclophosphamide, and with good recovery. CONCLUSIONS: The factors favoring inflammatory LETM are acute or subacute onset of clinical symptoms, positive oligoclonal bands in the CSF, positive NMO-IgG or other antibodies, and brain MRI showing demyelinating lesions. Postcontrast axial MRI sequences of the spinal cord can also be helpful. In doubtful situations, a trial of therapy and follow-up MRI a month later might be a more prudent approach if the patient is not rapidly deteriorating. PMID- 22082693 TI - Mantle cell lymphoma. PMID- 22082694 TI - Factors affecting patients' pain intensity during in office intravitreal injection procedure. AB - PURPOSE: To determine factors associated with patients' comfort during routine in office intravitreal injection. METHODS: Sixty patients receiving intravitreal injections over 15 months for macular edema because of diabetes, age-related macular degeneration, or retinal vein occlusion who were randomized into 3 groups to receive 1 of 3 commonly used forms of anesthesia-TetraVisc, proparacaine HCl, or tetracaine HCl-before receiving intravitreal injection were studied. Fifteen minutes after injection, patients were asked to rate their pain from 0 (no pain/no distress) to 10 (agonizing pain/unbearable distress) using a Visual Analog Pain score survey. Self-reported pain scores were stratified by age, gender, diagnosis, injection number, substance injected, needle gauge, and visual acuity improvement. RESULTS: Intravitreal injection was associated with low pain scores. Patients receiving tetracaine reported a statistically significant lower pain score (3.05 +/- 2.01) than patients receiving proparacaine (3.17 +/- 2.18) or TetraVisc (3.3 9+/- 2.26; P < 0.01). Other important factors influencing pain score significantly (P < 0.01) included improved vision from previous injection, female sex, and age >65 years. Pain scores decreased with each consecutive injection. CONCLUSION: Pain associated with intravitreal injection is generally mild, and may be associated with epidemiologic and environmental factors. PMID- 22082695 TI - Loss, gain, and the reframing of perspectives in long-term stroke survivors: a dynamic experience of quality of life. AB - PURPOSE: Little is known about stroke survivors' subjective quality of life experience. The purpose of this study was to understand the lived experience of quality of life in 6 long-term stroke survivors. METHOD: Using a phenomenological design, we interviewed participants (who were 21 months to 11 years post stroke) twice and gave them journals to write in between interviews. Data were evaluated using thematic analysis. RESULTS: The main theme, "It makes me feel like a human again," integrates 2 subthemes - activity loss: "That's what I miss" and awakening: "Reality comes to your world." The main theme describes quality of life as a constantly changing experience, and the subthemes elaborate on the process of change. CONCLUSION: Themes described quality of life as a dynamic experience that changed as activities of value were lost or gained and as participants experienced changes in their perspectives, beliefs, values, and behaviors. The discussion examines these themes through the lens of the Model of Human Occupation and the Shifting Perspectives Model of Chronic Illness. Clinical implications of the results are also discussed. PMID- 22082696 TI - Expanding poststroke depression research: movement toward a dyadic perspective. AB - Research on depression following stroke has traditionally been oriented toward understanding the experiences of individual survivors or their spousal caregivers outside of the context of their committed relationship. Moving toward a dyadic orientation to the problem of poststroke depression, in which the stroke survivor spouse dyad is viewed as the primary unit of analysis, will open the door to new lines of inquiry and may eventually lead to more effective treatments for survivors and their spouses. The first half of this article discusses the rationale for moving poststroke depression research toward a more dyadic perspective and highlights current efforts in this area. The second half of this article discusses some methodological challenges associated with dyadic data and the practical benefits of one statistical methodology, multilevel modeling, for examining depression in survivor-stroke dyads. PMID- 22082697 TI - A follow-up study of psychological problems after stroke. AB - PURPOSE: Psychological problems are common complications following stroke and have an impact on all aspects of recovery. This article investigates levels of psychological distress in patients during hospital admission and after discharge into the community. Early detection and review of poststroke psychological problems may optimize recovery from stroke as recommended in the national stroke guideline. Currently, there are very few follow-up investigations on poststroke mood disorders available that could inform clinical practice. METHOD: Psychological symptoms were defined as poststroke anxiety and depression and were measured using the Hospital Anxiety and Depression Scale (HADS). Revised cutoff scores for this clinical group were applied. Seventy-seven stroke patients were assessed in the hospital. Forty-two patients from this sample were reassessed after their discharge into the community. RESULTS: Patients in the hospital sample presented with mean anxiety and depression scores above the recommended cutoff for stroke. Far more than 50% of male and female patients presented with heightened psychological distress. Psychological symptoms were slightly less intense and less frequent in the follow-up after discharge sample. The differences between the HADS outcomes of hospitalized and community patients were nonsignificant but remained beyond cutoff for more than 50% of follow-up patients. CONCLUSION: The study highlights the importance of mood assessments for all stroke patients. The percentage of patients with residual psychological problems was lower than that reported in the literature. However, it is highly recommended for those patients with chronic poststroke psychological distress to have access to specialist psychological interventions. PMID- 22082698 TI - Boosting exercise beliefs and motivation through a psychological intervention designed for poststroke populations. AB - BACKGROUND: The effect of patient education on reducing stroke has had mixed effects, raising questions about how to achieve optimal benefit. Because past evaluations have typically lacked an appropriate theoretical base, the design of past research may have missed important effects. METHOD: This study used a social cognitive framework to identify variables that might change in response to education. A mixed design was used to evaluate 2 approaches to an intervention, both of which included education. Twenty-six seniors completed a measure of stroke knowledge and beliefs twice: before and after an intervention that was either "standard" (educational brochure plus activities that were not about stroke) or "enhanced" (educational brochure plus activities designed to enhance beliefs about stroke). Outcome measures were health beliefs, intention to exercise to reduce stroke, and stroke knowledge. RESULTS: Selected beliefs changed significantly over time but not differentially across conditions. Beliefs that changed were (1) perceived susceptibility to stroke, and (2) perceived benefit of exercise to reduce risk. Benefit beliefs, in particular, were strongly and positively associated with intention to exercise. CONCLUSION: Findings suggest that basic approaches to patient education may influence health beliefs. More effective stroke prevention programs may result from continued consideration of the role of health beliefs in such programs. PMID- 22082699 TI - Stroke patients' awareness of risk and readiness to change behaviors. AB - PURPOSE: Behavior change is an important component of secondary stroke prevention. The transtheoretical model, which describes behavior change as occurring through a series of stages, may be a useful way of assessing patients' readiness to change behavior. The model has been successfully applied to other chronic conditions and argues that people progressing "forward" through the stages are more likely to successfully change their behavior. The aim of this study was to describe stroke patients' readiness to change behaviors for stroke related risk factors using this model, in the absence of a behavior modification intervention. METHOD: Patients (n = 27) from an acute stroke ward of a major metropolitan hospital in Brisbane, Australia, were interviewed prior to and at 3 months following hospital discharge regarding their awareness of stroke risk factors and their readiness to change stroke risk-related behaviors. RESULTS: At both points in time, 30% of patients could not spontaneously nominate one or more stroke risk factors. Despite a trend of "forward" progression in stages of change between the 2 interviews for behaviors relating to hypertension, heart disease, and high cholesterol, there were no statistically significant changes over time for any of the behaviors. Patients' readiness to change stroke risk-related behaviors differed for each risk factor. CONCLUSION: Acknowledging that patients' readiness to change may differ for each risk factor may promote more effective facilitation of stroke secondary prevention behaviors. PMID- 22082700 TI - Understanding hope after stroke: a systematic review of the literature using concept analysis. AB - PURPOSE: Hope is said to be important in recovery from illness or injury, supporting adjustment, perseverance, and positive outcomes. There has been little exploration of hope in people after stroke. This is reflected in the literature, which lacks consistent definition and terminology. This purpose of this article is to clarify the concept of hope after stroke and to synthesize the findings to propose a working model of hope. METHOD: A systematic literature search was completed. Articles were included if they explored hope from the perspective of people with stroke or if hope was reported as a key finding in a study. Coding, analytic questions, and matrices were used to extract data and to compare, contrast, and synthesize conceptualizations, processes, and outcomes of hope. This was guided by a concept analysis methodology. RESULTS: The literature search identified 20 articles that met the inclusion criteria. Analysis of these articles suggested hope was conceptualized in 3 interrelated ways - as an inner state, as being outcome-oriented, and as an active process. Findings suggested that internal and external resources contributed to the development of hope. Hope was perceived to be linked with positive outcomes and functioned as a motivator and source of strength through recovery. Hope reflected elements also found in the concepts of expectations, goals, and optimism. CONCLUSION: This novel approach to analysis has furthered the understanding of hope. It has proposed a working model of hope that could be used by clinicians in considering hope with their clients and patients. PMID- 22082701 TI - An ecological approach to activity after stroke: it takes a community. AB - BACKGROUND: Biopsychosocial recovery from stroke is remarkable for some individuals, but the majority of stroke survivors have difficulty resuming activities. Even survivors with mild disability become disengaged. METHODS: Situational analysis grounded theory and ecological models were used to examine the barriers and facilitators to choice of everyday activities of stroke survivors aged 50 to 64 years. RESULTS: Resuming activities was an iterative process of scaffolding small tasks into activities through bargaining for access to practical support and inclusion into social situations. Although participants geared up to manage their condition and access activities, for the most part they were not in charge of the services and supports they required. They had little control over who was accepted to rehabilitation, for which services they qualified or disability policies. CONCLUSIONS: There are layers of interactions between individuals and multiple factors in their environments that influence participation. Low poststroke activity levels may be amenable to intervention. Further research should consider the following: (1) participation in activities through the lens of all levels of the socioecological model; (2) the impact of disability and aging-related stigma; (3) the results of ad hoc community navigation; and (4) the effects of restrictive health and disability policies on meaningful activity. PMID- 22082702 TI - Testing the effectiveness of knowledge and behavior therapy in patients of hemiplegic stroke. AB - OBJECTIVES: The purpose of this study was to examine demographic variables associated with anger and well-being in patients with stroke, to investigate the hypothesis that knowledge and behavior (K&B) therapy improves patients' emotional and physical well-being, and to discover psychological variables associated with therapeutic outcomes. METHODS: Seventy-seven patients with hemiplegic stroke were randomly assigned to either a control condition (the conventional therapy) or an experimental condition (K&B therapy). Both the experimental and control groups received physical therapy, which included prescribed medications and rehabilitation training programs for body functions. In addition, the experimental group received counseling, which consisted of a knowledge component and a behavioral training component. RESULTS: Patients' gender and ratings of stressful events were related to emotional health and well-being. Compared to the control group, the experimental group generally reported greater improvements in state anger, external anger, anger control, depression, quality of life, and activities of daily living. CONCLUSIONS: Consistent with our expectations, patients with stroke who received K&B training showed greater improvements in mental and physical health. Our findings suggest that the K&B therapy effectively targeted anger and improved the well-being among patients with stroke. It is our recommendation that K&B therapy should be implemented with a hospital's standard procedure for stroke recovery. PMID- 22082703 TI - Living successfully with aphasia: family members share their views. AB - Language and lifestyle changes experienced following the onset of aphasia extend beyond the individual to impact family members of persons with aphasia. Research exploring the meaning of living successfully with aphasia has explored the perspectives of individuals with aphasia and speech-language pathologists. Family members' views of living successfully with aphasia may also contribute valuable insights into positive adaptive processes and factors that may influence clinical interventions and community-based services for individuals with aphasia and their families. PURPOSE: To explore, from the perspectives of family members of individuals with aphasia, the meaning of living successfully with aphasia. METHOD: Twenty-four family members (nominated by individuals with aphasia) participated in semistructured in-depth interviews about living successfully with aphasia. Interviews were transcribed verbatim and analyzed using interpretative phenomenological analysis to identify themes relating to the meaning of living successfully with aphasia. RESULTS: Seven themes were identified from analysis of family member participant transcripts: getting involved in life, support for the person with aphasia, communication, family members' own needs, putting life in perspective, focusing on and celebrating strengths and improvements, and experiences with services. CONCLUSION: Findings provide evidence to support previous research indicating that aphasia affects the whole family and not just an individual. The inclusion of family members as part of the rehabilitation team is indicated. Family members' needs and priorities must be considered in conceptualizing living successfully with aphasia to ensure family members are included in intervention programs. PMID- 22082704 TI - Self-evaluation of driving simulator performance after stroke. AB - BACKGROUND AND PURPOSE: Despite the potential dangers associated with premature return to driving after stroke, very little research has examined the relationship between impaired self-awareness (ISA) and driving. This study examined self-awareness of driving simulator and neuropsychological performance among stroke patients, comparing them with healthy control participants. METHODS: Thirty stroke survivors and 30 controls each were asked for prediction and postdiction ratings of their performance on various driving simulator and neuropsychological tasks. Self-estimates versus actual performance discrepancy scores were calculated for various simulator and neuropsychological measures by converting scores to a shared metric. RESULTS: Across all measures, the stroke survivors greatly overestimated their performance in comparison with the accuracy of self-evaluations among the controls, thus suggesting ISA. This pattern of overestimating was observed on both novel (neuropsychological) and familiar (driving) tasks. However, there was some evidence to suggest that stroke survivors can benefit from feedback, as seen by increased accuracy in postdiction versus prediction self-evaluation scores. Both stroke survivors and controls also showed a greater shift toward accurate self-estimation on postdiction of driving performance than on postdiction of neuropsychological test performance. CONCLUSION: Although the temporal stability of the shift in awareness is not known, these results support the use of driving simulators as a useful and safe method of assessing and potentially improving stroke survivors' ISA. PMID- 22082705 TI - The effect of vocational rehabilitation on return-to-work rates post stroke: a systematic review. AB - PURPOSE: Returning to work has been identified as an important rehabilitation goal following stroke. Twenty percent of stroke survivors are of working age. The purpose of this systematic review was to determine the effect of vocational rehabilitation programs on return-to-work rates post stroke. METHOD: Searches were performed in electronic databases and Web-based sites. Studies were eligible for inclusion if they included an adult population of working age (18 to 65 years) who had survived a stroke and had participated in a vocational rehabilitation program. The exclusion criteria included any other type of rehabilitation that did not specifically address vocation, other diagnostic groups or studies where stroke population results were not reported independently, as well as publications not translated to English. The primary outcome was return-to-work rates. RESULTS: Six studies, involving a total of 462 participants, were included in this review. All studies were a retrospective single cohort design. The rates of employment following these vocational rehabilitation programs ranged from 12% to 49%. CONCLUSION: There was not an adequate number of high-quality trials to make recommendations that support or refute the use of specific vocational rehabilitation programs to increase return to-work rates following a stroke. Standardized terminology definitions as well as quality, randomized controlled trials are required before conclusions can be made about the effect of vocational rehabilitation programs on the return-to-work rates for stroke survivors. PMID- 22082706 TI - Cognitive behavior therapy, exercise, or both for treating chronic widespread pain. AB - BACKGROUND: The clinical impact of telephone-delivered cognitive behavioral therapy (TCBT), exercise, or a combined intervention in primary care patients with chronic widespread pain (CWP) is unclear. METHODS: A total of 442 patients with CWP (meeting the American College of Rheumatology criteria) were randomized to receive 6 months of TCBT, graded exercise, combined intervention, or treatment as usual (TAU). The primary outcome, using a 7-point patient global assessment scale of change in health since trial enrollment (range: very much worse to very much better), was assessed at baseline and 6 months (intervention end) and 9 months after randomization. A positive outcome was defined as "much better" or "very much better." Data were analyzed using logistic regression according to the intention-to-treat principle. RESULTS: The percentages reporting a positive outcome at 6 and 9 months, respectively, were TAU group, 8% and 8%; TCBT group, 30% and 33%; exercise group, 35% and 24%; and combined intervention group, 37% and 37% (P < .001). After adjustment for age, sex, center, and baseline predictors of outcome, active interventions improved outcome compared with TAU: TCBT (6 months: odds ratio [OR], 5.0 [95% CI, 2.0-12.5]; 9 months: OR, 5.4 [95% CI, 2.3-12.8]), exercise (6 months: OR, 6.1 [95% CI, 2.5-15.1]; 9 months: OR, 3.6 [95% CI, 1.5-8.5]), and combined intervention (6 months: OR, 7.1 [95% CI, 2.9 17.2]; 9 months: OR, 6.2 [95% CI, 2.7-14.4]). At 6 and 9 months, combined intervention was associated with improvements in the 36-Item Short Form Health Questionnaire physical component score and a reduction in passive coping strategies. Conclusions on cost-effectiveness were sensitive to missing data. CONCLUSION: TCBT was associated with substantial, statistically significant, and sustained improvements in patient global assessment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ISRCTN67013851. PMID- 22082707 TI - Implantable cardioverter/defibrillators in the primary prevention of sudden death: we know what to do but are we doing it? PMID- 22082708 TI - Early signals of harmful drugs. PMID- 22082709 TI - Balancing transparency and uncertainty. PMID- 22082710 TI - Thinking our way to better treatments of chronic pain. PMID- 22082711 TI - Optimal medical therapy use among patients receiving implantable cardioverter/defibrillators: insights from the National Cardiovascular Data Registry. PMID- 22082712 TI - Potential safety signals and their significance. PMID- 22082713 TI - Aortic stiffness is increased in acromegaly regardless the method of assessment. PMID- 22082714 TI - The incidence and characteristics of supraventricular tachycardia in left atrial isomerism: a high incidence of atrial fibrillation in young patients. AB - BACKGROUND: In left atrial isomerism (LAI), both atria show left atrial morphology. Although bradyarrhythmias are frequent and highly complex in LAI patients, previous studies have reported a low incidence of supraventricular tachycardia (SVT). METHODS: To evaluate the incidence and characteristics of SVT in LAI, we retrospectively evaluated the clinical characteristics of SVTs in 83 patients with LAI (age at last follow-up, 15.3+/-10.5 years). RESULTS: There were 27 SVTs in 19 patients (23%), including nine episodes of atrial fibrillation (AF) and eight non-reentrant SVTs. Sixteen of the 19 patients with SVT had histories of atriotomy, but the three patients with AF or non-reentrant tachycardia had no history of atriotomy. The rates of freedom from SVT were 66% and 59% at ages of 20 and 30 years, respectively; the corresponding rates for freedom from AF were 89% and 74%. In multivariate analysis, the predictors of SVT were age (OR, 1.14; 95% CI, 1.06-1.26; p=0.003) and sinus node dysfunction (SND) (OR, 3.88; 95% CI, 1.57-13.34; p=0.01). CONCLUSIONS: In patients with LAI, SVTs are common, and AF and non-reentrant SVTs are the major type of SVTs. The incidence of AF was high in young patients with LAI. The lack of anatomical barriers in the atria that allow the formation of macro-reentrant circuits may account for the higher incidence of AF and non-reentrant SVT than macro-reentrant tachycardia. Moreover, the increasing prevalence of SND with age should contribute to a higher incidence of SVT. PMID- 22082715 TI - Early onset of puberty in young girls: an Italian cross-sectional study. AB - BACKGROUND: International literature and clinical practice have referred to Marshall and Tanner data to define the physiological age at onset of puberty. A study in the United States (1997) showed an anticipation in pubertal onset, whereas several European studies did not confirm this trend. AIM: To describe the onset of secondary sexual characteristics in a large Italian population of girls and to compare it to reference literature data. SUBJECTS AND METHODS: A cross sectional study on 7311 2-14-yr-old girls who spontaneously requested a clinical evaluation for routine health check-up or acute illness by family pediatrician's offices in a northern Italian region (Lombardy), between September 2005 and November 2006. Trained family pediatricians performed a complete physical examination; pubertal status was evaluated following Tanner's criteria; breast development was assessed by palpation. RESULTS: Mean age of thelarche (B2), pubarche (PH2), menarche were 9.75, 10.09, and 12.49 yr, respectively. The prevalence of B2 and PH2 at ages 7-7.99 was 5.9% and 5.6%, respectively, at ages 8-8.99 was 15.5% and 13.8%, respectively. Mean time lapse from B2 to B3 and B2 to menarche was 1.46 and 2.74 yr, respectively. Mean age at menarche of our population and their respective mothers was almost identical. CONCLUSIONS: Our population presented earlier clinical signs of pubertal development than those defined by Marshall and Tanner. Mean age of menarche was not different in comparison to the previous generation. A different progression of pubertal development was found, in which the shift to B3 may have more clinical relevance. PMID- 22082716 TI - Livestock veterinarians at high risk of acquiring methicillin-resistant Staphylococcus aureus ST398. AB - The prevalence and risk factors associated with livestock-associated MRSA (LA MRSA) carriage was examined in Danish and Belgian veterinarians. The MRSA and LA MRSA carriage rates were 9.5% (95% CI 5.3-15.6) and 7.5% (95% CI 3.8-13.1) for MRSA and LA-MRSA, respectively, in Belgium and 1.4% (95% CI: 0.17-5.05) in Denmark (all Danish MRSA isolates belonged to the LA-MRSA genotype). All LA-MRSA isolates were resistant to tetracycline and 53.4% (7/13) showed a multi-resistant phenotype. LA-MRSA was significantly associated with veterinarians in contact with livestock (P=0.046). In the multivariable analysis, working with small animals in a veterinary clinic seems to be negatively associated (OR 0.15, 95% CI 0-1.0, P=0.05) and a strong direct association was found for LA-MRSA acquisition and exposure to live pigs (OR 12.1, 95% CI 1.6-548.5, P=0.01). Since carriage of MRSA ST398 may increase the risk of complications during hospitalization, our results underline that preventive measures may need to be developed for veterinary professionals, particularly for livestock veterinarians. PMID- 22082717 TI - The 30-year war on AIDS: have we reached the tipping point? PMID- 22082719 TI - Early awareness and uptake of an effective waiting room video intervention by STD clinics. AB - BACKGROUND: Successful diffusion and adoption is critical for the effectiveness and impact of a new intervention. The objective of this research was to evaluate the uptake and implementation of a newly released educational waiting room video in US sexually transmitted diseases (STD) Clinics. METHODS: A telephone survey was administered to a random sample of 73 clinic directors representing 76 US STD clinics 3 to 5 months following the availability of the intervention. A qualitative analysis was used to categorize survey responses and detect associations among them. RESULTS: Of the 76 clinics, 22% were aware of the intervention and 17% had ordered the intervention kit. The most frequently reported sources for hearing about the video were interpersonal communication/word of mouth, national conferences, and the STDPreventionOnline.org Website. The majority (74%) of clinic directors reported using state or local entities as primary sources of new information; however, reporting these channels was associated with unawareness of the new intervention. Facilitators to adoption included having adequate video/DVD equipment (55%) and a separate, nonshared waiting room for STD services in which to show the video (47%). CONCLUSIONS: The data from this sample suggest that making greater use of prominent thought leaders and interpersonal communication, including social networking, and professional groups may improve awareness of new interventions. Some barriers to adoption, such as lack of equipment, have relatively inexpensive solutions yet bureaucratic or technical support issues may still play a role. However, some structural barriers, such as shared waiting areas, will require innovative alternatives to conventional practice. PMID- 22082718 TI - The association between Trichomonas infection and incarceration in HIV seropositive and at-risk HIV-seronegative women. AB - BACKGROUND: The prevalence of Trichomonas vaginalis is higher among incarcerated women than in the general community. We sought to determine whether a history of incarceration itself was independently associated with trichomoniasis. METHODS: The HIV Epidemiology Research Study is a prospective cohort study of 871 HIV seropositive and 439 high-risk seronegative women in 4 urban centers (Bronx, NY; Detroit, MI; Providence, RI; Baltimore, MD). All participants enrolled between April 1993 and January 1995, with interviews and physical examinations conducted at baseline and at follow-up visits every 6 months up to 7 years. RESULTS: Of 1310 subjects, 427 (33%) reported being incarcerated on at least one occasion. In addition, 724 (55%) were found to have a sexually transmitted infection on at least one occasion during the study; baseline rates were 21% for T. vaginalis, 4.3% for Chlamydia trachomatis, 0.6% for N. gonorrhea, and 8% for syphilis. Incarceration was associated with the detection of trichomonas infection (between subject, odds ratio, 2.4; 95% confidence interval: 1.85-3.14; P < 0.01 and within subject, odds ratio, 1.56; 95% confidence interval: 1.26-1.92; P < 0.01). The association with incarceration remained significant after adjusting for age, race, HIV status, enrollment risk group, number of sexual partners, marital status, education, bacterial vaginosis, vaginal candidiasis, drug use (crack, cocaine, heroin), alcohol use, health insurance, receipt of public assistance, employment status, visit number, and study site. CONCLUSIONS: A history of incarceration was independently associated with the detection of trichomonas infection in a cohort of high-risk women. These data have implications for increased sexually transmitted infection prevention, screening, and treatment upon entry to jail as well as in the communities most affected by incarceration. PMID- 22082720 TI - Self-screening for Neisseria gonorrhoeae and Chlamydia trachomatis in the human immunodeficiency virus clinic--high yields and high acceptability. AB - BACKGROUND: Despite antiretroviral therapy (ART), incident human immunodeficiency virus (HIV) continues to rise, and sexually transmitted infections (STI) are well known for their part in HIV transmission. National guidelines recommend routine STI screening in HIV-positive individuals, but despite this, reported uptake remains low. METHODS: We implemented a nurse-led self-screening program for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in asymptomatic HIV patients. Self-collected samples were tested for CT and GC using the GenProbe Aptima Combo 2 assay. Clinical records were reviewed for ART history, CD4 T-cell count, and plasma viral load. A screening service evaluation questionnaire was handed out. RESULTS: During an 8-month period, 976 screens were performed. In all, 143 infections were detected which would have been missed without the screening program. Overall prevalence of infection among men who have sex with men was 17.4%: rectal CT and GC, 9.8% (56/571) and 4.2% (24/571), respectively; urethal CT and GC, 2.6% (16/605) and 1.3% (8/605), respectively; and pharyngeal CT and GC, 1.7% (10/589) and 3.9% (23/589), respectively. Among heterosexual men and women, the rates of CT were 2.1% (3/141) and 1.5% (3/201), and there was no GC. Transient viremia was observed at the time of STI diagnosis in 6 patients on ART. All men who have sex with men and most women found self-swabbing acceptable, and most patients indicated that they would like to be offered testing in future. CONCLUSION: These findings highlight the need for the introduction of similar screening approaches in HIV clinics. Self-collected specimens using sensitive and specific GC and CT nucleic acid amplification tests are a convenient and acceptable way of testing, and it may address some of the barriers to screening in this population. PMID- 22082721 TI - Racial/ethnic and gender differences among older adults in nonmonogamous partnerships, time spent single, and human immunodeficiency virus testing. AB - BACKGROUND: A higher frequency of nonmonogamy, due in part to lower marriage prevalence, may contribute to elevated human immunodeficiency virus (HIV)/sexually transmitted disease rates among older blacks. METHODS: To examine race and gender differences in nonmonogamy, time spent single (i.e., not married or cohabiting), and HIV testing in older adults, we analyzed US population-based data from the 2005-2006 National Social Life, Health, and Aging Project for 2825 heterosexual participants ages 57 to 85 years. RESULTS: Blacks spent greater portions of their adult lives single than did Hispanics or whites and were far more likely to report recent nonmonogamous partnerships (23.4% vs. 10.0% and 8.2%). Among individuals reporting sex in the prior 5 years, nonmonogamous partnerships were strongly associated with time spent single during the period. Control for time spent single and other covariates reduced the association of black race with nonmonogamous partnerships for men, but increased it for women. Less than 20% reported ever testing for HIV; less than 6% had been recommended testing by a provider. Testing rates, highest in black men and white women, differed little by history of nonmonogamous partnerships within gender strata. CONCLUSIONS: Singlehood helps to explain higher nonmonogamous partnership rates in older black men but not in older black women. Older adults rarely receive or are recommended HIV testing, a key strategy for reducing heterosexual HIV transmission. PMID- 22082722 TI - Sexually transmitted infections and risk behaviors among African American women who have sex with women: does sex with men make a difference? AB - OBJECTIVE: We sought to determine the prevalence of infection with Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, syphilis, and HIV among African American women who have sex with women (AAWSW), and compare sociodemographics, sexual risk behavior characteristics, and STI diagnoses among women reporting sex exclusively with women (exclusive AAWSW) to women reporting sex with both women and men (AAWSWM) during the past 12 months. METHODS: Eligible women presenting to the Mississippi State Department of Health STD Clinic between February 2009 and October 2010 were invited to participate. A survey on sociodemographics, sexual history, and sexual risk behavior characteristics was completed. Women were tested for the presence of C. trachomatis, N. gonorrhoeae, T. vaginalis, M. genitalium, syphilis, and HIV. RESULTS: A total of 196 African American women were enrolled; 56.6% of all women reported engaging in sexual activity exclusively with women (AAWSW) during the past 12 months and 40.8% reported engaging in sexual activity with both men and women (AAWSWM). As compared with exclusive AAWSW, AAWSWM were significantly more likely to report prior infection with C. trachomatis (35.0% vs. 13.5%, P < 0.001), prior infection with N. gonorrhoeae (28.75% vs. 2.7%, P < 0.001), and transactional sex (18.8% vs. 2.7%, P = 0.001). Additionally, 13.8% of AAWSWM reported having sex with a homosexual or bisexual man during the past 12 months. Trichomoniasis was diagnosed in 18.3% of all women, C. trachomatis in 11.0%, M. genitalium in 7.6%, and N. gonorrhoeae in 3.7%. There were no cases of syphilis or HIV. AAWSWM were significantly more likely to be diagnosed with trichomoniasis (25.0% vs. 13.5%, P = 0.04), C. trachomatis (22.5% vs. 2.7%, P < 0.001), N. gonorrhoeae (7.5% vs. 0.9%, P = 0.01), or any STI (47.5% vs. 18.3%, P < 0.001) than exclusive AAWSW. CONCLUSIONS: AAWSW in this study were at high risk for STI. AAWSWM, as a subgroup, may demonstrate heightened sexual risk-taking behaviors and higher STI rates compared with exclusive AAWSW. Sexual health services provided to AAWSW should take into account partner gender heterogeneity when counseling and screening for STI. PMID- 22082723 TI - Impact of age, gender, and pregnancy on syphilis screening using the Captia Syphilis-G assay. AB - BACKGROUND: Discordant results have been reported between treponemal-specific enzyme immunoassays (EIA) screening and confirmatory tests such as the Treponemal pallidum particle agglutination (TPPA) assay. The performance of IgG EIA screening in specific populations, such as pregnant women, is not well defined. We reviewed laboratory results of 34,251 samples from individuals who underwent IgG EIA screening at a large Boston academic medical center, so as to calculate positive concordance of these screening tests with a confirmatory TPPA or subsequent rapid plasma reagin (RPR) test by age, gender, pregnancy, and obstetric or gynecologic (Ob/Gyn) service. METHODS: We conducted a retrospective, cross-sectional study of the Captia Syph-G EIA serum samples between 2004 and 2007. Binary regression modeling was used to identify independent associations between demographic variables and positive concordance of EIA screening with RPR and confirmatory TPPA tests. RESULTS: Of 34,251 samples, 631 (1.8%) had a positive IgG EIA screen. In all, 79% of samples with a positive EIA had a reactive TPPA, and 48% had a positive RPR. Patients less than 40 years of age, females, and women on an Ob/Gyn clinical service had significantly lower rates of positive concordance between EIA screening and TPPA reactivity when covariate adjusted in regression modeling, whereas women on Ob/Gyn service were significantly associated with lower positive concordance with RPR testing. CONCLUSIONS: The relatively low positive concordances between EIA screening and confirmatory studies were more pronounced in low-risk patients, and it is important to define test performance in diverse patient populations. PMID- 22082724 TI - An evaluation of the natural history of bacterial vaginosis using transition models. AB - BACKGROUND: The natural history of bacterial vaginosis (BV) is complex given the variability across and within women over time. This article considers 3 different transition models for analyzing longitudinal BV data. METHODS: Data from the Longitudinal Study of Vaginal Flora were used to evaluate 3 transition modeling strategies: (1) a Markov regression, (2) a Markov regression with random effects, and (3) a mover-stayer model. The effect of covariates on the transition process of BV, defined as a Nugent score of 7 to 10, was estimated using a logistic regression parameterization. Models were compared using various model assessment techniques. We analyzed a subset of women completing all 5 visits (n = 1731) as well as the complete data (n = 3626), in which 1 or more visit measurements were missing. RESULTS: The Markov regression model had a poor fit to the data. A random-effects or mover-stayer model accounted for additional unexplained heterogeneity and had a better fit to the data. Across all models, douching was significantly associated with BV fluctuation. In the mover-stayer model, both douching and number of sexual partners were associated with persisting with (lambda11 = 0.90, P < 0.001; lambda12 = -0.41, P < 0.03, respectively) or without (lambda01 = -0.73, P < 0.001; lambda02 = -0.33, P = 0.023, respectively) BV across all visits. Using a random-effects model, we demonstrated that an individual propensity to initiate BV was positively associated with their propensity to resolve BV. CONCLUSIONS: Transition models that account for additional heterogeneity provide an attractive approach for describing the effect of covariates on the natural history of BV. PMID- 22082726 TI - Would gay men change their sexual behavior to reduce syphilis rates? AB - BACKGROUND: The community at which public health strategies for reducing syphilis epidemics are potentially targeted may have different considerations with regards to their sexual and health priorities. We aimed to elicit information on the acceptability of behavior change interventions among gay men for reducing syphilis transmission. METHODS: We conducted an online survey (n = 2306 participants) and focus groups to determine whether further sexual behavior change to reduce syphilis is likely to be acceptable to gay men in Australia. RESULTS: One quarter of survey respondents (26%) indicated that they would be highly likely to reduce partner acquisition rates in order to reduce their chances of syphilis infection. However, among the 475 (21%) men who reported greater than 10 partners in the previous 6 months, only 11% indicated being "highly likely" to reduce partner numbers to avoid syphilis. Among 606 (26%) survey respondents who reported not always using condoms in the previous 6 months, 34% indicated being highly likely to always use condoms with casual partners to avoid syphilis. In the focus groups, men indicated little commitment to sexual behavior change but some willingness to consider short-term changes to reduce community syphilis levels. CONCLUSIONS: Interventions promoting partner reduction or increased condom use are unlikely to be adopted on a long-term basis by men at greatest risk. Behavioral interventions alone are unlikely to materially contribute to syphilis prevention among gay men. PMID- 22082725 TI - Effect of sexual activity on vaginal colonization with hydrogen peroxide producing lactobacilli and Gardnerella vaginalis. AB - BACKGROUND: Bacterial vaginosis is associated with sexual activity, but mechanisms for this association are unclear. STUDY DESIGN: Cross-sectional analysis of data from women reporting sex with women who provided information on sexual behaviors as part of a study of vaginal bacteria was conducted. Vaginal bacteria were detected by semiquantitative culture. Binomial regression with log link evaluated associations between detection of bacteria and sexual behaviors reported to occur before enrollment. Linear regression evaluated associations between these behaviors and quantity of bacteria. RESULTS: Of the 320 women, 216 (68%) were colonized with H2O2-producing lactobacilli and 142 (44%) with Gardnerella vaginalis. Colonization with G. vaginalis was associated with >20 digital-vaginal sex acts (risk ratio, 2.01; 1.22, 3.29) or >10 toy-vaginal acts in the past 3 months (risk ratio, 1.76; 1.32, 2.36). Quantity of H2O2-producing lactobacilli was 1.3 log lower in colonized women reporting >10 acts of insertive vaginal sex-toy use in the past 3 months (95% confidence interval: -2.04, -0.56), 1.19 log lower with toy-vaginal sex in past 7 days (-1.75, -0.62), and 0.78 log lower in women sharing toys with a partner (-1.25, -0.31). CONCLUSIONS: Vaginal insertive use and sharing of sex toys were associated with decreased quantities of H2O2-producing lactobacilli and higher risk of colonization with G. vaginalis. PMID- 22082727 TI - Will changes in gay men's sexual behavior reduce syphilis rates? AB - BACKGROUND: Reducing rates of partner change and increasing condom usage among gay men are obvious targets for potentially reducing syphilis transmission among gay men. METHODS: We developed an agent-based stochastic model to examine syphilis transmission among a population of gay men, representative of gay men in Australia. This model was used to explore the potential impact of changes in sexual behavior over 1 month, 3 month, and indefinite time frames on syphilis epidemics. RESULTS: Simulations of interventions showed that short-term reductions in rates of partner change and increased condom use would have negligible impact on the long-term trends of syphilis epidemics. If no interventions are introduced, then the model forecasts that the syphilis prevalence in the population could continue to rise, with an increase of 80% in the number of men infected with syphilis during the next decade. However, if changes in sexual behavior are maintained in the long-term, then syphilis epidemics can be mitigated. If condom use is sustained at 80% in partnerships that are HIV discordant or of unknown status, then the prevalence of syphilis is estimated to decrease by 9% over 10 years. Similarly, if partner acquisition rates decrease by 25%, then there will be a 22% reduction in syphilis prevalence. CONCLUSIONS: Interventions promoting partner reduction or increased condom use would be ineffective in the short-term, and would have limited prospects for success in the long-term unless very large changes in behavior are sustained. Complementary social research indicates that such long-term changes in behavior are unlikely to be adopted, and therefore other intervention strategies need to be developed to reduce syphilis among gay men. PMID- 22082728 TI - What difference can we make in reducing syphilis among gay men? And how? PMID- 22082729 TI - Role of sexual transmission of HIV among young noninjection and injection opiate users: a respondent-driven sampling study. AB - BACKGROUND: Sexual transmissibility of HIV among young drug users in China has been investigated in few studies. The objective of this study was to examine the role of sexual transmission on HIV infection among injection drug users (IDUs) and noninjection drug users (NIDUs). METHODS: Respondent-driven sampling (RDS) was used to recruit 426 young heroin/opium drug users in Yunnan, China. Logistic regression modeling was performed to examine interrelationships among risky sexual behaviors, drug-use modes, and drug-use practices. RESULTS: Substantial proportions of NIDUs and IDUs reported engagement in risky sexual behaviors including: (1) multiple sexual partners (42% of NIDUs vs. 37% of IDUs), (2) concurrent sexual partnerships (48% vs. 46%), (3) commercial sex partners (23% vs. 24%), and sex partners who were NIDUs (14% vs. 17%). Both NIDUs and IDUs reported low levels of condom use with nonregular partners (48% vs. 42%) and regular partner (24% vs. 27%), and having a history of recent methamphetamine use (21% vs. 18%). Compared to IDUs, NIDUs reported having had fewer sex partners who were IDUs, fewer IDU network peers, more NIDU network peers, and having lower levels of HIV knowledge and self-perceived HIV risk. CONCLUSIONS: Generalization of the HIV epidemic from high-risk groups to the general population may be driven by risky sexual behavior among drug users. Reducing sexual transmission of HIV among both IDUs and NIDUs is the next major challenge for HIV intervention among drug users in China. PMID- 22082730 TI - The cytotoxic effects of three different bisphosphonates in-vitro on human gingival fibroblasts, osteoblasts and osteogenic sarcoma cells. AB - INTRODUCTION: Osteonecrosis of the jaw (ONJ) is an emerging condition in patients undergoing long-term administration of bisphosphonates (BP) for the treatment of osteoporosis and hypercalcaemia associated with malignancy, multiple myeloma, and metastatic breast and prostate cancers. This is a follow-up study, its purpose was to examine the effects in-vitro of intravenous zoledronic acid (ZOL) and pamidronate (PAM) and oral alendronate (FOS) on the human oral cavity using gingival fibroblasts and osteoblasts cells and, in addition, osteogenic sarcoma cells (SaOS-2-cells). MATERIALS AND METHODS: Human gingival fibroblasts, osteoblasts and SaOS-2-cells were seeded on multiple 6-well plates at a density of 5 * 10(5)cells in a 4-week cell culture. Four different concentrations (1, 5, 10, 20 MUM) of each BP (ZOL, PAM, FOS) and pyrophosphate were used in this study. RESULTS: All BP decreased collagen production and lowered cell proliferation in vitro. ZOL was the component with most inhibitory effect. CONCLUSION: The findings in this study suggest that ZOL, PAM and FOS generally diminish cell proliferation and collagen production of human gingival fibroblasts, osteoblasts and SaOS-2-cells. The present follow-up study shows that not only ZOL and PAM but also FOS have a strong inhibitory effect on collagen production and cell survival in-vitro. PMID- 22082731 TI - Clinical, therapeutic and prognostic features of osteosarcoma of the jaws - experience of 36 cases. AB - INTRODUCTION: Osteosarcoma of the jaws (OSJ) differs from osteosarcoma of other skeletal regions due to later development, a high mortality associated with the local disease, fewer incidences of metastases and its extreme rarity. In regard to clinical and pathological parameters as well as therapeutic approaches and prognosis, OSJ has not been specifically examined to date. In order to achieve a better understanding of this special malignancy, an evaluation of incidence, treatment and prognosis of patients with OSJ in our department over the past 38 years was conducted. MATERIALS AND METHODS: A retrospective analysis of patients with OSJ between 1972 and 2010 was performed. Information regarding patient characteristics, site of the lesion, main presenting symptoms, latency of initial diagnosis, treatment, histology, local recurrence, development of metastatic disease, duration of follow up and survival was obtained. The data were compared to the literature. RESULTS: Thirty-six patients (2-81 years, mean: 33.9, standard deviation: 21.3) were diagnosed and treated for OSJ (maxillar:mandibular nearly 1:2). Initial symptoms were local swelling (81%) and pain (47%). The latency period between fist symptoms and clinical presentation was 3.7 months (1-24). A radical resection alone was conducted in 15 patients. In nine patients, resection and radiotherapy was used. Resection with chemotherapy was the treatment of choice in seven patients. Five patients received a triple combination of resection, chemo- and radiation therapy. The osteoblastic subtype of osteosarcoma was most frequent (42%). In 15 cases (42%) local recurrences, in two cases (5%) metastasis were seen. Of these patients, 13 died within the observation period. One other patient (3%) died as a result of progressive pulmonary metastasis. A mean total survival rate of 61% could be seen whereas the highest survival rate (80%) was found in patients who were treated with neoadjuvant chemotherapy, radical resection and adjuvant radiation. Positive prognostic factors were a younger age and tumour-free resection margins. DISCUSSION: OSJ is a highly lethal tumour entity. According to the data at hand, therapy should possibly include chemotherapy, radical resection and irradiation. Nevertheless, due to the rarity of OSJ, information remains limited and the treatment of choice should be within the focus of clinical multi-centre studies. PMID- 22082732 TI - Mucormycosis of the head and neck: report of five cases with different presentations. AB - Mucormycosis is a lethal fungal disease with a general poor prognosis. Rhinocerebral presentation is the more frequent form. The purpose of this study was to review and show our experience in the management of 5 cases of mucormycosis of the head and neck with different clinical presentations. The high suspicion led us a prompt diagnosis and aggressive surgical treatment that allowed a good outcome in our series. PMID- 22082733 TI - Neonates with seizures: what to consider, how to image. AB - The immature brain is more prone to seize than the mature brain. Causes of seizure are multiple and affect different neuroimaging modalities. The most common associated diseases are hypoxia-ischemia, intracranial hemorrhage and cerebral infarction, central nervous system infections, and acute metabolic disturbances. Ultrasound (US) is not specific. Computed tomography (CT) carries the risk of irradiation and is not as productive as magnetic resonance (MR) imaging. MR imaging is the modality of choice; it is difficult to perform in a neonate, but it is more sensitive and versatile than US or CT, and is now widely used in specialized centers. PMID- 22082734 TI - MR imaging of the term and preterm neonate with diffuse brain injury. AB - Both term and preterm neonates suffer from diffuse brain injury. Global hypoxic ischemic injury (HII) describes the diffuse brain injury most common in term neonates. HII is thought to result from decreases in blood flow and oxygen supply. Diffuse white matter injury of prematurity describes the most common diffuse brain injury in preterm neonates. The cause is likely multifactorial. Magnetic resonance (MR) imaging is the most sensitive imaging technique for early diagnosis of brain injury in neonates. This article discusses neonatal diffuse brain injury, the role of MR imaging in predicting neurodevelopmental outcome, and research results using MR imaging techniques. PMID- 22082735 TI - MR imaging workup of inborn errors of metabolism of early postnatal onset. AB - Immediate or early postnatal onset forms of neurometabolic disorders represent a clinically important subgroup because these often present as a life-threatening episode of metabolic decompensation shortly after birth. This article focuses on this group of diseases, often referred to as "devastating neurometabolic diseases" of the newborn. Awareness of the most common entities and their clinical, biochemical, and diagnostic imaging manifestations is important because if undiagnosed and untreated, the diseases may have catastrophic consequences. Although formal diagnosis relies on laboratory tests, diagnostic imaging is often pivotal in both reaching the correct diagnosis and/or orienting further targeted investigative efforts. PMID- 22082736 TI - MR imaging of neonatal brain infections. AB - Infections of the brain in the postnatal period differ from those in older children as a result of a combination of distinct epidemiologic factors in general, and immaturity of neonatal brain and immunologic host response in particular. It has been recognized that clinical and neurologic signs are often nonspecific, sometimes scarce, and seldom correlate with the extent of neuroimaging findings, thus warranting an early MR imaging examination in the course of the disease, enabling rapid therapy institution and better clinical outcome. This article reviews most of postnatal pathogen agents involved in neonatal brain infections, related physiopathology, and neuroimaging findings. PMID- 22082737 TI - Birth-related injury to the head and cervical spine in neonates. AB - Birth-related injury is defined as any traumatic or ischemic event sustained during the process of delivery. Perinatally acquired disease processes secondary to birth-related injury can be traumatic or ischemic in nature. In this article, the authors focus on traumatic/mechanical injuries. Other diseases of the perinatal time period, including germinal matrix hemorrhages and hypoxic-ischemic encephalopathy, are beyond the objective of this review. PMID- 22082738 TI - Imaging of neonatal child abuse with an emphasis on abusive head trauma. AB - Child abuse and neglect is a serious clinical and socioeconomic problem that is sometimes underestimated. One of the most devastating forms is abusive head trauma. This review addresses the radiological workup in cases of suspected child abuse. The use of all modalities, and their advantages and disadvantages, is discussed. A special section is devoted to the radiological report in cases of child abuse, as a clinical record and a legal document. PMID- 22082739 TI - Congenital cardiovascular malformations: noninvasive imaging by MRI in neonates. AB - Owing largely to advances in fetal echocardiography, in most developed countries the diagnosis of severe congenital heart disease (CHD) is now made during gestation, and delivery is electively planned in hospitals that have the facilities and expertise to manage these patients, with magnetic resonance (MR) imaging performing an important complementary role. MR imaging as a sole imaging modality for comprehensive presurgical evaluation is also increasingly being explored. This article focuses on the imaging of neonatal CHD by MR, followed by a brief discussion of the safety of gadolinium-based contrast agents in this age group. PMID- 22082740 TI - Congenital cardiac defects and MR-guided planning of surgery. AB - In neonates and infants with congenital heart disease (CHD), cardiovascular magnetic resonance (CMR) is an established imaging modality in all patients in whom echocardiography does not provide sufficient information and definitive diagnosis. CMR is noninvasive, and does not involve vascular catheterization or ionizing radiation. Therefore the use of CMR obviates the potential risks of cardiac catheterization in critically ill infants. This article discusses the use of CMR in newborns with CHD before cardiac surgery, focusing on conotruncal anomalies, pulmonary venous anomalies, complex CHD in visceroatrial heterotaxy, borderline hypoplastic left heart syndrome, and the use of contrast medium in newborns. PMID- 22082741 TI - MR imaging of the neonatal musculoskeletal system. AB - Experience in magnetic resonance (MR) imaging of the neonatal musculoskeletal system is rapidly increasing. The exquisite ability of MR to image the soft tissues, especially cartilage, without radiation is its key strength. Although it is not practical or sensible to undertake MR imaging in conditions in which radiography and ultrasound provide adequate information, MR is proving to be a useful adjunct and problem-solving tool in many neonatal musculoskeletal conditions. PMID- 22082742 TI - MR imaging of the newborn. PMID- 22082746 TI - Pleomorphic adenoma of the submandibular gland in children: a case report and a review of the Japanese literature. AB - An 8-year-old girl was introduced to our department due to the presence of a left painless submandibular mass. The mass had been initially noticed at 7 years of age. Preoperative imaging showed the mass to have originated from the left submandibular gland. The mass was removed with a part of submandibular gland attached to it. The pathologic findings showed the mass to be pleomorphic adenoma without any malignant components. The postoperative clinical course was uneventful. During the 1-year follow-up period, no recurrence was noticed. In addition to the clinical report of our case, we reviewed the pertinent Japanese literature to clarify the clinical features of this disease in children. PMID- 22082744 TI - Histiocyte-rich xanthomatous pseudotumor mimicking relapse on positron emission tomography imaging in an adolescent with primary mediastinal diffuse large B-cell lymphoma. AB - Inflammatory pseudotumors (IPTs) are rare, enigmatic lesions that may develop as a late manifestation of a reparative process. We describe the case of a teenager with primary mediastinal subtype of diffuse large B-cell lymphoma who developed an IPT at the site of the original lymphoma, mimicking relapse of disease on positron emission tomography/computed tomography imaging. This is the first report of IPT in a teenager with mediastinal lymphoma. This case is an important reminder of the limitations of positron emission tomography/computed tomography imaging in patients with lymphoma and stresses the importance of histologic confirmation of suspected treatment failure or relapse. PMID- 22082743 TI - Juvenile cobalamin deficiency in a 17-year-old child with autonomic dysfunction and skin changes. AB - We report a rare case of juvenile cobalamin deficiency who presented at the age of 17 years. He was underweight and had skin changes, normocytic anemia, and autonomic dysfunction, which led to adynamic ileus and acute postrenal failure. The expected macrocytosis was masked by an underlying alpha-thalassemia trait. The patient had an excellent response to parenteral cobalamin treatment. PMID- 22082747 TI - A multimethod assessment of psychosocial functioning and late effects in survivors of childhood cancer and hematopoietic cell transplant. AB - Previous research in childhood cancer and hematopoietic cell transplant (HCT) survivorship has relied on the use of standardized questionnaires that assess symptoms of psychological functioning but do not sufficiently capture the cancer survivorship experience. Study aims are to quantitatively and qualitatively assess the psychosocial functioning of pediatric cancer and HCT survivors seen in a multidisciplinary survivorship clinic, determine survivorship concerns, and assess potential demographic and medical correlates of psychosocial outcomes. Data were collected using a retrospective chart review of a parent-report questionnaire of the child's psychological functioning, responses to a semistructured interview that qualitatively assessed adjustment to life after treatment, and documented medical late effects. Results indicated the majority of survivors had healthy psychological adjustment based upon a parent-report questionnaire. However, nearly 72% of survivors reported 1 or more survivorship concerns during the interview, with the primary concerns being current and future health or physical functioning, including the possibility of cancer recurrence. A content analysis of the interview responses indicated HCT survivors had more school or cognitive functioning concerns compared with survivors who did not have an HCT. Further research should use survivorship-specific measures to better identify survivors at risk and determine the impact of late effects on their quality of life. PMID- 22082748 TI - Breast-feeding for the management of painful procedures. PMID- 22082749 TI - Right pulmonary artery to left atrial fistula: a description of two cases, emphasising a diagnostic approach. AB - Right pulmonary artery to left atrial fistula is a rare pathology characterised by a right to left shunt. Another important aspect of this pathology is the difficulty encountered in making a diagnosis, which is why the diagnosis is frequently delayed into adulthood. A description of two cases is used to emphasise the importance of the different modes of echocardiography as a diagnostic tool in diagnosis, as well as the two different clinical forms that it adopts: a group of patients suffering cardiac failure and cyanosis without apparent cause generally in neonates and a second group of mostly older patients with dyspnoea and cyanosis without apparent cause. Symptoms thus differ depending on the time of presentation and are related to the size of the fistula. PMID- 22082751 TI - Flaporhexis: rapid and effective technique to limit epithelial ingrowth after LASIK enhancement. AB - We describe a method of lifting and replacing the laser in situ keratomileusis (LASIK) flap to reduce the incidence of epithelial ingrowth beneath the flap after LASIK enhancement. In the rapid flaporhexis technique, the flap edge is opened by 1 clock hour with a Sinskey hook and the flap is peeled back after the exposed edge is grasped with a forceps. When necessary, further blunt retraction of the flap is performed with a triangular polyvinyl acetate sponge. After ablation and before the flap is replaced, a triangular sponge is used to clear epithelial remnants from the interface. This method consistently produces a smooth epithelial dissection and decreases the possibility that epithelium is retained beneath the flap. PMID- 22082750 TI - Preoperative iris configuration and intraocular pressure after cataract surgery. AB - PURPOSE: To determine predictors of long-term intraocular pressure (IOP) after cataract surgery. SETTING: Hunter Holmes McGuire Veterans Administration Hospital, Richmond, Virginia, USA. DESIGN: Case series. METHODS: Clinical variables, IOP by applanation tonometry, anatomic features on anterior segment optical coherence tomography (AS-OCT), and gonioscopy were assessed before and after uneventful cataract surgery in eyes with open filtration angles. Multivariate linear regression of preoperative measurements was used to predict the mean IOP from 2 to 18 months postoperatively. RESULTS: The study enrolled 77 eyes (77 patients). Prediction of the mean postoperative IOP improved when up to 4 preoperative IOP values were averaged (r(2) = 0.20) compared with using the final preoperative IOP value only (r(2) = 0.13). The mean iris cross-sectional area decreased after surgery, from 3.84 mm(2) to 3.70 mm(2) (P=.01). The mean convex hull of the iris segments also decreased, from 5.05 mm(2) to 4.19 mm(2) (P<.001). The mean postoperative IOP was independently predicted by the preoperative average IOP, primary open-angle glaucoma, and the convex hull of cross-sectional iris segments (P=.001, model r(2) = 0.38) or iris cross-sectional area (P=.003, model r(2) = 0.36). Phacoemulsification parameters, incision type, and anterior chamber angle and depth did not predict postoperative IOP. CONCLUSIONS: Averaging up to 4 preoperative IOP values improved postoperative IOP predictions. A high iris cross-sectional area or convex hull of the iris segments on AS-OCT was associated with lower postoperative IOP. These findings might help identify patients who are likely to have the largest IOP drop after cataract surgery. PMID- 22082753 TI - Testosterone and cardiovascular risk in patients with erectile dysfunction. AB - BACKGROUND: The relationship between cardiovascular (CV) diseases (CVD) and testosterone (T) levels in men has not been completely clarified. AIM: To evaluate the association between T levels and CV risk in subjects with erectile dysfunction (ED) and to verify whether their body mass index might (BMI) represents a possible confounder in T-related CV stratification. MATERIAL AND METHODS: A consecutive series of 2269 male patients attending the Outpatient Clinic for ED was studied. The assessment of CV risk was evaluated using the engine derived from the Progetto Cuore study. RESULTS: After adjustment and for BMI and associated morbidities, SHBG-bound and -unbound T levels decreased as a function of CV risk assessed thorough Progetto Cuore risk engine. In addition, a higher prevalence of hypogonadism related symptoms and signs was associated with a higher CV risk. Among factors included in the Progetto Cuore risk engine age, total and HDL cholesterol and diabetes were all significantly associated with CV risk-dependent modification of total and calculated free-T levels. When the relationship between SHBG bound and unbound T and CV risk was evaluated as a function of obesity (BMI>30 kg/m(2)), all the aforementioned associations were confirmed only in non obese patients. CONCLUSIONS: Hypogonadism could be associated either with an increased or reduced CV risk, depending on the characteristics of subjects. Low T observed in obese patients might represent the result of higher CV risk rather than a direct pathogenetic mechanism. PMID- 22082752 TI - Comparison of clinical outcomes with 2 small-incision diffractive multifocal intraocular lenses. AB - PURPOSE: To evaluate and compare the clinical results of 2 diffractive multifocal small-incision intraocular lenses (IOLs) implanted after biaxial microincision cataract surgery (MICS). SETTING: Ataturk Training and Research Hospital, 2nd Ophthalmology Department, Ankara, Turkey. DESIGN: Comparative case series. METHODS: Eyes that had biaxial MICS with implantation of an Acri.Lisa 366D IOL (Group 1) or Acriva Reviol MFM 611 IOL (Group 2) were followed for at least 6 months postoperatively. Uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuities; corrected distance visual acuity; distance-corrected intermediate and near visual acuities; and contrast sensitivity measurements with and without glare were determined. Early and late complications and subjective complaints were recorded and evaluated. RESULTS: The study enrolled 60 eyes of 32 patients. The preoperative and intraoperative data were comparable in the 2 IOL groups. There were no statistically significant postoperative differences in the mean spherical equivalent (Group 1, -0.30 diopter (D) +/- 0.30 [SD]; Group 2, 0.26 +/- 0.28 D; P=.584), mean UDVA (0.80 +/- 0.14 and 0.86 +/- 0.17, respectively; P=.158), and mean Jaeger UNVA (1.46 +/- 0.73 and J 1.23 +/- 0.50, respectively; P=.155). However, there was a significant difference in mean Jaeger UIVA (3.06 +/- 0.90 and 2.23 +/- 0.72, respectively; P=.000). Mesopic contrast sensitivity and the incidence of complications and dysphotopsia symptoms were not significantly different between the 2 IOL groups. CONCLUSIONS: Both IOLs provided excellent distance and near visual acuity and contrast sensitivity. The Group 2 IOL gave better intermediate distance results. PMID- 22082754 TI - Microwave induced shift of the main phase transition in phosphatidylcholine membranes. AB - Numerous experimental evidence show that exposure of biological systems to extremely high frequency microwaves may induce significant effects even at low powers. These effects are thought to occur via nonthermal mechanisms involving primarily the interaction of microwaves with phospholipid membrane structures. However, no conclusive experimental evidence that biomembranes exhibit remarkable sensitivity to this radiation has been provided up to now. Here, deuterium nuclear magnetic resonance spectroscopy is used to study the effects of microwaves on 1,2-Dimyristoyl-sn-glycero-3-phosphatidylcholine/(2)H(2)O multilamellar vesicles that serve as biomimetic membranes. Here we show that, if the membrane is brought into close proximity to the transition point, microwaves induce a reduction of water ordering at the membrane interface, an upward shift of the main phase transition temperature and a broadening of the transition region. A deep dosimetric analysis shows that the above effects are nonthermal, indicating the need for a nonthermal hypothesis to explain them. This study suggests that exposure to high-frequency microwaves can have far reaching consequences on active biological systems. PMID- 22082755 TI - Early-stage Hodgkin disease in a 24-year-old woman. PMID- 22082756 TI - Low-grade follicular lymphoma of the small intestine: a challenge for management. PMID- 22082757 TI - MicroRNAs and cancer: introduction. PMID- 22082758 TI - MicroRNAs in the pathogenesis of cancer. AB - MicroRNAs (miRs) are small (19-25 nucleotides) non-protein-coding RNAs involved in development, differentiation, and aging; they act by inducing messenger RNA (mRNA) silencing through degradation, and post-transcriptional or decoy activity. miR profiles of human solid and hematologic malignancies have highlighted their potential value as tumor markers in cancer patient management. Different experimental lines of evidence have confirmed that deregulation of miRs not only results as consequence of cancer progression but also directly promotes tumor initiation and progression in a cause-effect manner. These findings reveal a potential and appealing role for miRs as cancer therapeutic targets. This review focuses on the causes and consequences of miR deregulation in carcinogenesis and tumor progression. The work aims at providing the molecular bases for the understanding of the potential role of miRs in the translational and clinical setting. PMID- 22082760 TI - MicroRNAs in mutagenesis, genomic instability, and DNA repair. AB - MicroRNAs (miRNAs) are aiding our understanding of cancer biology, and are now coming close to therapeutic use as well. Here, we focus specifically on the interaction between miRNAs and genomic instability. MiRNA regulation is essential to many cellular processes, and escape from this regulatory network seems to be a common characteristic of malignant transformation. Genomic instability may preferentially target miRNAs either because of selective pressure or because of inherent vulnerability related to their location near fragile sites. Furthermore, disruption of miRNA processing elements affords a more global release from miRNA regulation. Finally, we review how miRNAs function as both effectors and modulators of the DNA damage response, intricately weaved with traditional elements such as ATM, P53, and MMR. Thus, miRNAs are important substrates for genomic instability and play a crucial role in cellular DNA sensing and repair mechanisms. PMID- 22082759 TI - Alterations of microRNAs contribute to colon carcinogenesis. AB - MicroRNAs are being evaluated as biomarkers and therapeutic targets for colon cancer. MicroRNAs have a functional role in the initiation and progression of colon cancer. Altered microRNA expression is found in tumors and their expression patterns may serve as useful cancer biomarkers. Polymorphisms in microRNAs or microRNA binding sites may modify the risk of developing cancer. As we continue to improve our understanding of the role for microRNAs in the initiation and progression of cancer, one goal is to gain insights that will allow for the development of microRNAs as biomarkers and therapeutic targets for cancer. This review provides a current understanding of the connection between microRNAs and colon cancer. We will cover evidence that global microRNA expression patterns are altered in colon tumors, that specific microRNAs have a functional role in colon carcinogenesis, that polymorphisms in microRNAs may be associated with risk of colon cancer, and the potential for using circulating microRNAs as a noninvasive biomarker for the detection of cancer. PMID- 22082762 TI - MicroRNAs: toward the clinic for breast cancer patients. AB - Expression of microRNAs (miRNAs) has been found to be deregulated in all human cancers, where they may behave either as oncogenes or as tumor-suppressor genes. In the last 5 years, miRNA investigations in breast cancer represented an exciting area of discovery, which produced new knowledge on the molecular basis of this disease, tools for molecular classification, and new markers with diagnostic and prognostic relevance, as well as the discovery of novel breast cancer-predisposing genes. In this review, we describe current knowledge of the role of microRNAs in breast cancer. PMID- 22082761 TI - The role of microRNAs in human liver cancers. AB - Hepatocellular carcinoma (HCC) is a primary malignancy of the liver of global importance. Recent studies of the expression and role of microRNA (miRNA) in HCC are providing new insights into disease pathogenesis. In addition, therapeutic efforts targeting specific miRNAs are being evaluated in animal models of HCC. The potential of miRNAs as biomarkers of disease or prognostic markers is being explored. Herein, we review studies of miRNA expression in human HCC, and discuss recent advances in knowledge about the involvement and role of selected miRNAs in disease pathogenesis, as biomarkers, or as therapeutic targets for HCC. PMID- 22082763 TI - Clinical implications of microRNAs in lung cancer. AB - Lung cancer still represents a very deadly disease in strong need of new, effective, therapeutic approaches. MicroRNAs (miRNAs) represent a new category of noncoding RNAs with gene expression regulatory functions. Several studies have shown that miRNAs are frequently deregulated in lung cancer patients with respect to healthy individuals. These aberrations of the miRNome (defined as the full spectrum of miRNAs in a given genome) occur at several levels, including primary tumors and patient body fluids (such as blood and sputum), suggesting that miRNAs can be effectively used as biological markers with diagnostic, prognostic, and predictive implications. This review focuses on these translational aspects of research on the field of miRNAs and lung cancer. PMID- 22082764 TI - Potential applications of microRNAs in cancer diagnosis, prognosis, and treatment. AB - Early studies have established that microRNAs (miRNAs) are widely deregulated in cancer and play a critical role in cancer pathogenesis. Recent research efforts are directed now towards translating these basic discoveries into novel tests or treatments that could improve the diagnosis and outcome of cancer patients. In this review, we will summarize the potential applications of miRNAs for cancer diagnosis, prognosis, and treatment. In addition, we will discuss current pitfalls and future directions. PMID- 22082765 TI - Using virtual reality to provide health care information to people with intellectual disabilities: acceptability, usability, and potential utility. AB - BACKGROUND: People with intellectual disabilities have poor access to health care, which may be further compromised by a lack of accessible health information. To be effective, health information must be easily understood and remembered. People with intellectual disabilities learn better from multimodal information sources, and virtual reality offers a 3-dimensional (3D) computer generated environment that can be used for providing information and learning. To date, research into virtual reality experiences for people with intellectual disabilities has been limited to skill-based training and leisure opportunities within the young to mid age ranges. OBJECTIVE: This study assessed the acceptability, usability, and potential utility of a virtual reality experience as a means of providing health care-related information to people with intellectual disabilities. We designed a prototype multimodal experience based on a hospital scenario and situated on an island in the Second Life 3D virtual world. We wanted to know how people of different ages and with varying levels of cognitive function would participate in the customized virtual environment, what they understood from being there, and what they remembered a week later. METHODS: The study drew on qualitative data. We used a participatory research approach that involved working alongside people with intellectual disabilities and their supporters in a community setting. Cognitive function was assessed, using the Matrix Analogies Test and the British Picture Vocabulary Scale, to describe the sample. Participants, supported by facilitators, were video recorded accessing and engaging with the virtual environment. We assessed recall 1 week later, using a specialized interview technique. Data were downloaded into NVivo 8 and analyzed using the framework analysis technique. RESULTS: Study participants were 20 people aged between 20 and 80 years with mild to severe intellectual disabilities. All participants were able to access the environment and voluntarily stayed there for between 23 and 57 minutes. With facilitator support, all participants moved the avatar themselves. Participants engaged with the scenario as if they were actually there, indicating cognitive presence. Some referred back to previous medical experiences, indicating the potential for experiential knowledge to become the foundation of new learning and retention of knowledge. When interviewed, all participants remembered some aspects of the environment. CONCLUSIONS: A sample of adults with intellectual disabilities of all ages, and with varying levels of cognitive function, accessed and enjoyed a virtual-world environment that drew on a health care-related scenario, and remembered aspects of it a week later. The small sample size limits generalizability of findings, but the potential shown for experiential learning to aid retention of knowledge on which consent is based appears promising. Successfully delivering health care-related information in a non-National Health Service setting indicates potential for delivery in institutional, community, or home settings, thereby widening access to the information. PMID- 22082766 TI - The impact of rhythm complexity on brain activation during simple singing: an event-related fMRI study. AB - PURPOSE: Since rhythmical aspects of singing have been neglected up to now our objective was to investigate if it was possible to specify areas concerned with rhythm processing during simple singing. METHODS: In an event-related fMRI experiment we tested 30 healthy non-musicians with rhythm sequences, which had to be repeated as monotonously sung vowel changes with (1) regular groupings, (2) regular groupings and rests, and (3) irregular groupings. RESULTS: Common activations for all conditions were found in bilateral supplementary motor area, premotor cortex more distinct in the left hemisphere, left cingulate gyrus, and right basal ganglia. Only irregular groupings making the highest demands on attention, working memory, and sequencing capabilities resulted in additional activation of pars orbitalis and insula more distinct in the left hemisphere, as well as bilateral cingulate gyrus, and parietal lobes. Our analyses demonstrated that bilateral pars orbitalis (BA 47), insula, and left cingulate gyrus are core areas whose activity correlates with rhythm complexity. CONCLUSIONS: Rhythm structure is a decisive factor concerning lateralization as well as activation of specific areas during simple singing. This finding suggests a directed use of the singing voice e.g., in order to support language rehabilitation in patients. PMID- 22082767 TI - 4-iodophenyl isothiocyanate: a neuroprotective compound. AB - PURPOSE: Naturally occurring isothiocyanates (ITCs) are known to possess chemopreventive and neuroprotective properties. Our objective was to study the synthetic ITC 4-iodophenyl isothiocyanate (4-IPITC) in different models of neurodegeneration. METHODS: In vitro, we exposed primary cortical neurons to various insults such as excessive glutamate exposure, oxygen-glucose deprivation, oxidative stress and 1-methyl-phenylpyridinium (MPP+). In vivo, experimental autoimmune encephalomyelitis (EAE) was induced in dark agouti rats treated with 4 IPITC in 3 different concentrations (10, 20 and 40 mg/kg), orally for 28 days. In a Parkinson's model, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected in mice pretreated with 4-IPITC (5 mg/kg, orally) for 1 week. Nest building behavior at day 1, 3 and 6 after MPTP injection was assessed along with dopamine and metabolites, and tyrosine hydroxylase (TH) staining on termination day 6. RESULTS: 4-IPITC successfully reduced cell death in all in vitro assays. Moreover, in two independent neurite outgrowth assays the compound showed neurotrophic properties. In the EAE study, 4-IPITC significantly delayed the day of onset and decreased the cumulative EAE score. Although the number of animals in this MPTP study was limited, 4-IPITC showed potential for dampening toxicity. CONCLUSIONS: Taken together, our in vitro findings suggest robust neuroprotective and neurotrophic properties of 4-IPITC, which was confirmed in two in vivo models of neurodegeneration. PMID- 22082768 TI - Imaging in gynecology. PMID- 22082769 TI - Imaging of acute pelvic pain. AB - Determining the cause of acute pelvic pain in the female patient is often a clinical challenge. Diagnostic imaging can be invaluable in this situation. Ectopic pregnancy, pelvic inflammatory disease, and hemorrhagic ovarian cysts are the most commonly diagnosed gynecologic conditions presenting with acute pelvic pain. Ovarian torsion and degenerating fibroids occur less frequently. Other causes to consider include endometriosis, and postpartum causes such as endometritis, or ovarian vein thrombosis. Finally, nongynecologic conditions may overlap in their presentation of acute pelvic pain and should also be considered. The most important of these is acute appendicitis. PMID- 22082770 TI - Imaging of benign adnexal masses: characteristic presentations on ultrasound, computed tomography, and magnetic resonance imaging. AB - Adnexal masses are common in the general population. Although ovarian cancer is a significant cause of mortality, large screening studies demonstrate that the majority of adnexal masses are benign. These benign masses include physiologic cysts, paraovarian masses, and benign ovarian lesions. It is important that gynecologists and radiologists appreciate the appearance of these lesions on multiple imaging modalities, including ultrasound, computed tomography, and magnetic resonance imaging to avoid unnecessary intervention. PMID- 22082771 TI - Imaging of Mullerian duct anomalies. AB - Mullerian duct anomalies (MDAs) are relatively common disorders that are particularly relevant in patients with infertility, recurrent pregnancy loss, or a history of preterm labor. Accurate characterization of MDAs is crucial to the implementation of appropriate treatment. Various imaging modalities have been used in the evaluation of MDAs, including hysterosalpingography, ultrasound, and magnetic resonance imaging (MRI). Although hysterosalpingography and ultrasound may suggest a Mullerian duct anomaly, further evaluation by MRI is often required. MRI is the best imaging method available because of its superior ability to reliably visualize complex uterovaginal anatomy. PMID- 22082772 TI - Imaging of endometrial pathology. AB - The normal endometrium changes regularly with the menstrual cycle and atrophies after menopause. It is important to be aware of the normal spectrum of endometrial appearances at imaging to accurately detect and diagnose pathologic conditions. This article reviews imaging features of the normal and abnormal endometrium, and conditions which may mimic endometrial pathology. Emphasis will be on ultrasound with sonohysterography and magnetic resonance imaging as these are the imaging modalities of choice for evaluation of the endometrium. The complementary role of hysterosalpingography, computed tomography, and 18 fluorodeoxyglucose-positron emission tomography will also be discussed. PMID- 22082773 TI - Ovarian cancer: detection and radiologic staging. AB - Ovarian cancer is the second most common gynecologic malignancy. It is the deadliest, largely owing to late stage at the time of diagnosis. Ultrasound is modality of choice in the evaluation of suspected adnexal masses. Magnetic resonance imaging is an excellent problem solver when an adnexal mass is indeterminate on ultrasound. Staging of ovarian cancer remains surgical, though preoperative imaging can identify inoperable patients and identify suspicious sites for intraoperative biopsy. This article reviews the use of different imaging modalities in the detection and staging of ovarian carcinoma, and discusses imaging indications, radiologic features, and the shortcomings of imaging. PMID- 22082774 TI - Imaging of cervical pathology. AB - A variety of benign and malignant entities affect the uterine cervix. These are discussed and illustrated. Cross-sectional and functional imaging can improve the accuracy of traditional clinical cervical cancer staging. Emphasis is placed on magnetic resonance imaging for initial staging and fused positron emission tomography-computed tomography for restaging and surveillance. The imaging appearance of benign cervical pathology is reviewed with ultrasonography as the first-line imaging modality and magnetic resonance imaging for problem solving in difficult cases. PMID- 22082775 TI - Effect of colour LEDs on mycelia growth of Aspergillus ficuum and phytase production in photo-fermentations. AB - Aspergillus ficuum grown on plates and in liquid cultures were illuminated by a white fluorescent light and four different colour LED lights (white, blue, green and red) to evaluate the regulation of LED lights on fungal growth. Biomass conversion, pellet size and phytase activity were examined. In liquid culture, luminous intensity was highly correlated with the rate of biomass conversion but did not affect pellet size. The white fluorescent light contained several different wavelengths, and therefore, its effect on A. ficuum represents the cooperative effect of these wavelengths. Strong luminance of a white fluorescent light inhibited growth of A. ficuum mycelia on plates, whereas white LED light enhanced growth. The development of mycelia was also inhibited by blue LED light and enhanced by red LED light illumination. Investigating the effect of LED lights on the growth of A. ficuum could provide evidence on the luminous intensity that is sufficient for regulating fermentation by light. PMID- 22082776 TI - Lifetime-based sensing of the hyaluronidase using fluorescein labeled hyaluronic acid. AB - In this report we propose a lifetime-based sensing (LBS) for the detection of hyaluronidase (HA-ase). First, we heavily label hyaluronan macromolecules (HAs) with fluorescein amine. The fluorescein labeled HA (HA-Fl) has a weak fluorescence and short fluorescence lifetime due to an efficient self-quenching. Upon the addition of HA-ase, the brightness and lifetime of the sample increase. The cleavage of an HA macromolecule reduces the energy migration between fluorescein molecules and the degree of the self-quenching. A first order of the cleavage reaction depends on the amount of the HA-ase enzyme. We describe an HA ase sensing strategy based on the lifetime changes of the fluorescein labeled HA in the presence of HA-ase. We demonstrate that the calibration of the sensing response is the same for the average lifetime as for a single exponential decay approximation, which significantly simplifies the analysis of the sensing measurements. PMID- 22082777 TI - Nonneoplastic signet-ring cell change in gastrointestinal and biliary tracts: a pitfall for overdiagnosis. AB - Nonneoplastic signet-ring cell change (SRCC) is a rare but known phenomenon in gastrointestinal and biliary tracts and is always associated with underlying mucosal ulceration/erosion secondary to infection, ischemia, or other etiology. Because nonneoplastic SRCC closely mimics signet-ring cell adenocarcinoma (SRCA), differentiation of these 2 entities is critical because misdiagnosis of nonneoplastic SRCC as SRCA can lead to intense therapeutic interventions such as surgery and/or chemoradiation therapy. In this review, a brief overview on nonneoplastic SRCC in gastrointestinal and biliary tracts, including the spectrum of clinical presentation, important histologic features, and immunohistochemical markers that are useful in differentiating nonneoplastic SRCC from SRCA, is provided. The pathogenesis of nonneoplastic SRCC in gastrointestinal and biliary tracts is discussed. PMID- 22082778 TI - Post-ablation tubal sterilization syndrome. PMID- 22082779 TI - The final option. PMID- 22082780 TI - Prenatal screening for fetal aneuploidy. PMID- 22082781 TI - Prenatal screening for fetal aneuploidy. PMID- 22082782 TI - Evaluation of fetal liver volume by tridimensional ultrasound in women with gestational diabetes mellitus. AB - OBJECTIVE: To evaluate the effect of gestational diabetes mellitus (GDM) on fetal liver growth during the third trimester. METHODS: We performed a longitudinal study of pregnant women recruited at the time of GDM screening (24 to 28 weeks of gestation), with follow-up visits at 32 weeks, 36 weeks, and delivery. Women with GDM were followed with nutritional recommendations and insulin when necessary according to the Canadian Diabetes Association guidelines. Fetal liver volume was evaluated using 3-D ultrasound at each antenatal visit, and fetal liver growth was compared between women with and without GDM. RESULTS: Twenty-seven women were recruited, 10 with normal glucose tolerance (NGT) and 17 with confirmed GDM, five who required insulin and 12 who were treated by diet only. We found no difference in fetal liver volume between groups at any of the three visits, and median birth weight was also similar between groups. On the other hand, we found a strong correlation between fetal liver volume at 36 weeks' gestation and birth weight (rho = 0.61, P < 0.001). CONCLUSIONS: In our preliminary study, we found that fetal liver volume could be a strong predictor of infant birth weight independent of GDM status. This suggests that fetal liver volume of offspring of women with NGT is similar to that of offspring of women with GDM treated following recommended targets. Larger studies are required. PMID- 22082783 TI - Carbetocin versus oxytocin for prevention of postpartum hemorrhage in patients with severe preeclampsia: a double-blind randomized controlled trial. AB - OBJECTIVE: In patients with severe preeclampsia there is an increased risk of postpartum hemorrhage, but the hemodynamic changes associated with severe preeclampsia make the management of any kind of bleeding particularly troublesome. There are many pharmacological options for the management of postpartum hemorrhage, oxytocin being the first line of treatment. There is as yet no evidence about the safety and efficacy of using carbetocin, an oxytocin agonist, in these patients. We aimed to compare oxytocin with carbetocin for the routine prevention of postpartum hemorrhage in patients with severe preeclampsia. METHODS: We performed a prospective double-blind randomized controlled trial in 60 women with severe preeclampsia, recruited between July and September 2010. The women were randomized to receive either oxytocin or carbetocin during the third stage of labour. The primary outcome measure was postpartum hemorrhage requiring additional uterotonics, and the secondary outcome measures were the difference in hemoglobin levels between groups, the development of oliguria, and hemodynamic status (mean arterial pressure and heart rate) after administration of the drug. RESULTS: Carbetocin was as effective as oxytocin in the prevention of postpartum hemorrhage in women with severe preeclampsia. Carbetocin had a safety profile similar to that of oxytocin, and it was not associated with the development of oliguria or hypertension in this cohort. CONCLUSIONS: Carbetocin is an appropriate alternative to oxytocin for the prevention of postpartum hemorrhage in women with severe preeclampsia. Considering that it appears not to have a major hemodynamic effect in women with severe preeclampsia and that it uses a lower volume per dose than oxytocin, it should be considered a valid option in the management of the third stage of labour in women with hypertensive disorders of pregnancy. PMID- 22082784 TI - Comparison of maternity experiences of Canadian-born and recent and non-recent immigrant women: findings from the Canadian Maternity Experiences Survey. AB - OBJECTIVE: To compare the maternity experiences of immigrant women (recent, <= 5 years in Canada; non-recent > 5 years) with those of Canadian-born women. METHODS: This study was based on data from the Canadian Maternity Experiences Survey of the Public Health Agency of Canada. A stratified random sample of 6421 women was drawn from a sampling frame based on the 2006 Canadian Census of Population. Weighted proportions were calculated using survey sample weights. Multivariable logistic regression was used to estimate odds ratios comparing recent immigrant women with Canadian-born women and non-recent immigrant women with Canadian-born women, adjusting for education, income, parity, and maternal age. RESULTS: The sample comprised 7.5% recent immigrants, 16.3% non-recent immigrants, and 76.2% Canadian-born women. Immigrant women reported experiencing less physical abuse and stress, and they were less likely to smoke or consume alcohol during pregnancy, than Canadian women; however, they were more likely to report high levels of postpartum depression symptoms and were less likely to have access to social support, to take folic acid before and during pregnancy, to rate their own and their infant's health as optimal, and to place their infants on their backs for sleeping. Recent and non-recent immigrant women also had different experiences, suggesting that duration of residence in Canada plays a role in immigrant women's maternity experiences. CONCLUSION: These findings can assist clinicians and policy-makers to understand the disparities that exist between immigrant and non-immigrant women in order to address the needs of immigrant women more effectively. PMID- 22082786 TI - The Ottawa and Kingston (OaK) Birth Cohort: development and achievements. AB - OBJECTIVE: The Ottawa and Kingston (OaK) Birth Cohort collected data on maternal and infant genetic and epidemiologic variables in order to (1) explore the association between folate supplementation or thrombophilias and adverse, placenta-mediated pregnancy outcomes; (2) create a biobank of maternal and infant biological and genetic samples; and (3) stimulate future research using this cohort data. METHODS: A prospective cohort design was used to collect mother and infant data. Women were recruited at 12 to 20 weeks' gestation, during prenatal care visits at The Ottawa Hospital and Kingston General Hospital from October 2002 to April 2009. Data on maternal and infant demographics, maternal health, obstetrical history, and pregnancy outcomes were collected. Testing was done for biological/serological markers associated with adverse pregnancy outcomes. Maternal and cord blood samples were biobanked. RESULTS: A total of 8085 mothers were recruited to the OaK Birth Cohort. Analysis of the cohort data showed that taking multivitamin supplements containing folic acid was associated with a reduced risk of preeclampsia (aOR 0.37; 95% CI 0.18 to 0.75). The majority of participants agreed to have their genetic/biological samples biobanked (samples collected for n = 7241 mothers, n = 2175 infants) and to be re-contacted regarding future research opportunities. CONCLUSION: Birth cohorts are a useful tool in determining associations between risk factors and adverse maternal and fetal outcomes, and can serve as a repository of data for future research. Creating strong research partnerships helped enhance financial resources and increase participant recruitment potential. Epidemiological and biobanked data and samples from the OaK Birth Cohort are available for use by other investigators. PMID- 22082785 TI - Why do Canadian women fail to achieve optimal pre-conceptional folic acid supplementation? An observational study. AB - OBJECTIVES: To determine the factors that put Canadian women at risk for not supplementing with folic acid (FA) in the three months before conception, as recommended for the prevention of infant neural tube defects. METHODS: This study used data from the Canadian Maternity Experiences Survey. We used Poisson regression analysis with a robust variance to determine which factors were associated with women not supplementing with FA in the three months prior to pregnancy as compared with women who did supplement. RESULTS: Of the 6421 women surveyed, 57.7% were supplementing with FA pre-conceptionally. The risk factors associated with a lack of FA supplementation pre-conceptionally were maternal age <19 (prevalence ratio [PR] = 0.50; 95% CI 0.36 to 0.69) or 20 to 24 (PR = 0.75; 95% CI 0.67 to 0.84); education below high school level (PR = 0.73; 95% CI 0.61 to 0.87), at high school level (PR = 0.77; 95% CI 0.71 to 0.83), or at post secondary level other than university (PR = 0.93; 95% CI 0.88 to 0.97); being at or below the low-income cut-off (PR = 0.74; 95% CI 0.67 to 0.81); smoking before pregnancy (PR = 0.79; 95% CI 0.73 to 0.86); being non-fluent in the language of the health care provider (PR = 0.66; 95% CI 0.49 to 0.88); being obese (BMI >= 30) (PR = 0.91; 95% CI 0.85 to 0.98); being unemployed (PR = 0.94; 95% CI 0.89 to 1.00); and being born outside of Canada (PR = 0.79; 95% CI 0.74 to 0.84). CONCLUSION: Young maternal age, low education, low income, smoking, language barriers, obesity, unemployment, and being born outside Canada are risk factors for suboptimal or lack of FA supplementation pre-conceptionally. PMID- 22082787 TI - "They were my eggs; they were her babies": known oocyte donors' conceptualizations of their reproductive material. AB - OBJECTIVE: We sought the views of women who took part in an altruistic known oocyte donation program to provide insights into the dynamics of known oocyte donation in Canada. METHODS: Semi-structured interviews were conducted face-to face or by telephone with 15 Canadian women who had donated oocytes to a friend or a relative for family-building and 18 women who had received oocytes donated by a friend or a relative in the eight years prior to the interview. RESULTS: Donors and recipients recounted few problems with their experiences of oocyte donation. Donors' positive experiences were contingent on their desire to facilitate the family-building aspirations of a friend or relative and the trusting relationship they had with their recipient. These dynamics subsequently affected their perceptions regarding the embryos created using their oocytes and their relationship with any child born as a result of their donation. Most donors would not donate their oocytes to an anonymous recipient and would not support donating unused embryos created with their oocytes to an unknown recipient. CONCLUSION: Altruistic known donation is an important feature of oocyte donation programs in Canada, where commercial procurement of gametes is forbidden. Legal clarity, information, and psychosocial counselling are essential to minimize relationship problems in known oocyte donation. PMID- 22082788 TI - Revisiting the association between endometriosis and bipolar disorder. AB - OBJECTIVE: We sought to study the association between endometriosis and bipolar disorder. METHODS: Using the Structured Clinical Interview for DSM-IV Axis I Disorders, the prevalence of bipolar disorder was compared in 27 patients with endometriosis and 12 women with pelvic pain not related to endometriosis who were seen at a specialty gynaecology clinic for women with chronic pelvic pain. RESULTS: A significantly greater proportion of women in the endometriosis group were found to have bipolar disorder and a poorer quality of life than women with pelvic pain not related to endometriosis. CONCLUSION: There may be an association between endometriosis and bipolar disorder. An optimal approach to managing endometriosis should include evaluation and treatment of psychiatric comorbidity, particularly bipolar disorder. PMID- 22082789 TI - Randomized controlled trial of cystocele plication risks: a pilot study. AB - OBJECTIVE: We wished to determine the feasibility of a single-centre randomized controlled trial to investigate whether avoiding cystocele plication in women undergoing transvaginal repair of cystocele decreases the need for catheterization beyond the second postoperative day. METHODS: Patients undergoing transvaginal repair of cystocele were randomly assigned to either have or not have plication sutures during their procedure. We assessed the success of recruitment, physician acceptability, and adherence to protocol, and we also assessed the need for catheterization beyond the second postoperative day. RESULTS: Twenty-two women were randomized (a recruitment rate of 85%), and participating surgeons did not feel that one surgical technique was superior to the other. There were no protocol violations after randomization. No cases of postoperative voiding dysfunction were identified. CONCLUSION: A multicentre randomized controlled trial is required to determine the short-term and long-term risks and benefits of avoiding plication sutures in women undergoing transvaginal repair of cystocele. If patients and physicians support the study protocol, conducting such a trial is feasible. PMID- 22082790 TI - Oral contraceptives and venous thromboembolism: pill scares and public health. AB - Post-marketing surveillance of combined oral contraceptives (COCs) for rare complications such as venous thromboembolism (VTE) presents unique challenges. Prospective studies, which are costly and time consuming, have to date been undertaken by only a few contraceptive manufacturers willing to commit to full evaluation of product safety. Often such studies are conducted with the approval of regulatory authorities as a precondition for marketing. Alternatively, independent investigators with access to large databases have conducted retrospective studies to compare the incidence of VTE between new and older products. Such studies, however, run the risk of erroneous conclusions if they cannot ensure comparable risk profiles for users of these different products. Often database studies are unable to access information on important confounders, and medical records may not be available to validate the actual diagnosis of VTE. "Pill scares" generated following publication and media dissemination of worrisome findings, when the conclusions are in doubt and not corroborated by stronger prospective study designs, are frequently damaging to public health. From a review of recent publications on the VTE risk with drospirenone-containing COCs, it can be concluded that the best quality evidence does not support a difference in risk between users of COCs containing drospirenone and those of COCs containing levonorgestrel. PMID- 22082791 TI - The diagnosis and management of ovarian hyperstimulation syndrome. AB - OBJECTIVE: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management. OUTCOMES: These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes. EVIDENCE: Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words "ovarian hyperstimulation syndrome" and "gonadotropins," and guidelines created by other professional societies were reviewed. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). RECOMMENDATIONS: 1. Once the diagnosis of ovarian hyperstimulation syndrome is made, disease severity should be classified as mild, moderate, severe, or critical. (III-B) 2. The physician prescribing gonadotropins should inform each woman of her personal risk for ovarian hyperstimulation syndrome. (III-A) 3. In areas where patients do not have ready access to physicians familiar with the diagnosis and management of ovarian hyperstimulation syndrome, the physician prescribing gonadotropins should ensure that women are made aware that they should contact a physician or a member of the team within the hospital unit who has relevant experience, should the need arise. (III-B) 4. Outpatient management is recommended for women with mild and moderate ovarian hyperstimulation syndrome. If outpatient management for more severe ovarian hyperstimulation syndrome is to be undertaken, the physician should ensure that the woman is capable of adhering to clinical instructions and that there is a system in place to assess her status every 1 to 2 days. (III-A) 5. Paracentesis should be performed in admitted patients with tense ascites to alleviate their discomfort. (II-2B) 6. Outpatient culdocentesis should be considered for the prevention of disease progression in moderate or severe ovarian hyperstimulation syndrome. (II-2B) 7. Women with severe and critical ovarian hyperstimulation syndrome should be admitted to hospital for intravenous hydration and observation. (III-A) 8. Intravenous hydration should be initiated with a crystalloid solution to prevent hemoconcentration and provide adequate end organ perfusion. If end-organ perfusion is not maintained with a crystalloid solution, an alternate colloid solution should be administered. (II-2B) 9. Pain relief in admitted patients should be managed with acetaminophen and/or opioid analgesics. (III-B) Non-steroidal anti-inflammatory drugs with antiplatelet properties should not be used. (III-B) 10. Women with severe ovarian hyperstimulation syndrome should be considered for treatment with prophylactic doses of anticoagulants. (II-2B) 11. Critical ovarian hyperstimulation syndrome should be managed by a multidisciplinary team, according to the end organ affected. (III-C). PMID- 22082793 TI - Effect of attentional focus strategies on peak force and performance in the standing long jump. AB - Significant benefits in standing long jump performance have been demonstrated when subjects were provided verbal instructions that promoted an external focus of attention compared with an internal focus of attention, suggesting differences in ground reaction forces. The purpose of the present study was to evaluate peak force and jump performance between internal and external focus of attention strategies. Untrained subjects were assigned to both experimental conditions in which verbal instructions were provided to promote either an external or internal focus of attention. All subjects completed a total number of 5 standing long jumps. The results of the study demonstrated that the external focus of attention condition elicited significantly greater jump distance (153.6 +/- 38.6 cm) than the internal focus of attention condition (139.5 +/- 46.7 cm). There were no significant differences observed between conditions in peak force (1429.8 +/- 289.1 N and 1453.7 +/- 299.7 N, respectively). The results add to the growing body of literature describing the training and learning benefits of an external focus of attention. Practitioners should create standardized verbal instructions using an external focus of attention to maximize standing long jump performance. PMID- 22082794 TI - Enhancing jump performance after combined vs. maximal power, heavy-resistance, and plyometric training alone. AB - Saez Saez de villarreal, E, Izquierdo, M, and Gonzalez-Badillo, JJ. Enhancing jump performance after combined vs. maximal power, heavy-resistance, and plyometric training alone. J Strength Cond Res 25(12): 3274-3281, 2011-The purpose of this study was to examine the effects of 5 different stimuli on jumping ability and power production after 7 weeks of training. Sixty-five (47 men and 18 women) physical education students were randomly assigned to 5 experimental groups that performed: combination of all training methods (A); heavy-resistance training using full-squat exercise (i.e., 56-85% of 1 RM for 3-6 repetitions) (B); power-oriented strength training using a parallel-squat exercise (i.e., 100-130% of load that maximizes power output for 2-6 repetitions) (C); power-oriented strength training using a loaded countermovement jumping (i.e., 70-100% of load that maximizes power output for 2-5 repetitions; countermovement jump [CMJ]) (D); and plyometric jumping (E). The CMJ (cm), loaded CMJ (cm), maximum rate of force development (RFDmax) during early concentric phase of loaded CMJ (N.s) and power output during early concentric phase of loaded CMJ (watts) were measured before and after 7 weeks of training. Significant improvements in CMJ (from 7.8 to 13.2%) were observed in all groups. Significantly greater increases in power output during loaded jumps were observed in A (10-13%) and D (8-12%) groups compared with in the other groups. Significant increases in RFDmax were observed in A (20-30%), C (18-26%), and D (20-26%) groups. The results of this study provide evidence to suggest that if training program is designed and implemented correctly, both traditional slow velocity training and faster power-oriented strength training alone, or in combination with plyometric training, would provide a positive training stimulus to enhance jumping performance. PMID- 22082792 TI - Advanced reproductive age and fertility. AB - OBJECTIVE: To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART) and provide recommendations for their management, and to review investigations in the assessment of ovarian aging. OPTIONS: This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility. OUTCOMES: The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility. EVIDENCE: Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, ART). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). BENEFITS, HARMS, AND COSTS: Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology. RECOMMENDATIONS: 1. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. (II-2A) 2. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive. (III-B) 3. Ovarian reserve testing may be considered for women >= 35 years of age or for women < 35 years of age with risk factors for decreased ovarian reserve, such as a single ovary, previous ovarian surgery, poor response to follicle-stimulating hormone, previous exposure to chemotherapy or radiation, or unexplained infertility. (III B) 4. Ovarian reserve testing prior to assisted reproductive technology treatment may be used for counselling but has a poor predictive value for non-pregnancy and should be used to exclude women from treatment only if levels are significantly abnormal. (II-2A) 5. Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age. Women > 40 years should consider IVF if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation. (II-2B) 6. The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman's own eggs. (II-2B) 7. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established. (II-2A) 8. Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40. (III-B) 9. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small. (II-2C). PMID- 22082795 TI - Do compression garments enhance the active recovery process after high-intensity running? AB - Lovell, DI, Mason, DG, Delphinus, EM, and McLellan, CP. Do compression garments enhance the active recovery process after high-intensity running? J Strength Cond Res 25(12): 3264-3268, 2011-This study examined the effect of wearing waist-to ankle compression garments (CGs) on active recovery after moderate- and high intensity submaximal treadmill running. Twenty-five male semiprofessional rugby league players performed two 30-minute treadmill runs comprising of six 5-minute stages at 6 km.h, 10 km.h, approximately 85% VO(2)max, 6 km.h as a recovery stage followed by approximately 85% VO(2)max and 6 km.h wearing either CGs or regular running shorts in a randomized counterbalanced order with each person acting as his own control. All stages were followed by 30 seconds of rest during which a blood sample was collected to determine blood pH and blood lactate concentration [La]. Expired gases and heart rate (HR) were measured during the submaximal treadmill tests to determine metabolic variables with the average of the last 2 minutes used for data analysis. The HR and [La] were lower (p <= 0.05) after the first and second 6 km.h recovery bouts when wearing CGs compared with when wearing running shorts. The respiratory exchange ratio (RER) was higher and [La] lower (p <= 0.05) after the 10 km.h stage, and only RER was higher after both 85% VO(2)max stages when wearing CGs compared with when wearing running shorts. There was no difference in blood pH at any exercise stage when wearing the CGs and running shorts. The results of this study indicate that the wearing of CGs may augment the active recovery process in reducing [La] and HR after high-intensity exercise but not effect blood pH. The ability to reduce [La] and HR has important consequences for many sports that are intermittent in nature and consist of repeated bouts of high-intensity exercise interspersed with periods of low intensity exercise or recovery. PMID- 22082796 TI - Sulfonic acid functionalized poly(ethylene glycol dimethacrylate-1-vinyl-1,2,4 triazole) as a high-performance solid acid catalyst for the esterification of lactic acid with methanol. AB - Sulfonic acid functionalized poly(ethylene glycol dimethacrylate-1-vinyl-1,2,4 triazole), poly(EGDMA-VTAZ-SO(3)H), is evaluated in the esterification of lactic acid with methanol. From nitrogen physisorption data, high surface area (220 m(2)/g) and type IV isotherm are obtained. Conversion measurements indicate a stronger interaction of poly(EGDMA-VTAZ-20%SO(3)H) with water molecules than that occurring in poly(EGDMA-VTAZ-10%SO(3)H). Hence, the higher catalytic activity of poly(EGDMA-VTAZ-10%SO(3)H) is related to the more hydrophobic microenvironment of -SO(3)H sites, which reduces the acid site deactivation associated with adsorption of water generated during the reaction. Moreover, apparent activation energy is found to be 48.02 kJ mol(-1), which can be comparable with the literature values. PMID- 22082798 TI - Packing effects on argon and methanol adsorption inside graphitic cylindrical and slit pores: a GCMC simulation study. AB - Using Grand Canonical Monte Carlo simulation, we have studied the effects of confinement on argon and methanol adsorption in graphitic cylindrical and slit pores. Linear chain, zigzag and incomplete helical packing are observed for argon adsorption in cylindrical pores. However, for methanol adsorption different features appear because the electrostatic interactions favour configurations that maximize the hydrogen bonding among methanol molecules. We have found zigzag chains with hydrogen-bonded structures for methanol adsorption in cylindrical and slit pores. To investigate how dense the adsorbed phase is and how many molecules could be packed per unit physical volume of the solid, we consider two different definitions of pore density; one based on the physical volume and the other on the accessible volume. That based on accessible volume gives a measure of the fluid density, while that based on the physical volume gives a measure of how much adsorbate can be stored per unit volume of the adsorbent. It is found that the adsorbate is denser in cylindrical pores, but that slit pores can pack more molecules per unit solid volume. We also discuss the effects on the isosteric heat of argon and methanol of pore size, pore geometry and loading. PMID- 22082797 TI - Photoswitching in azobenzene self-assembled monolayers capped on zinc oxide: nanodots vs nanorods. AB - We report the synthesis and spectroscopic characterization of nanohybrid structures consisting of an azobenzene compound grafted on the surface of zinc oxide nanoparticles. Characteristic bathochromic shifts indicate that the azobenzene photochromic molecules self-assemble onto the surface of the nanocrystals. The extent of packing is dependent on the shape of the nanoparticle. ZnO nanorods, with flat facets, enable a tighter organization of the molecules in the self-assembled monolayer than in the case of nanodots that display a more curvated shape. Consistently, the efficiency of photochromic switching of the self-assembled monolayer on ZnO nanoparticles is also shown to be strongly affected by nanoparticle shape. PMID- 22082799 TI - Modeling carbon dioxide adsorption on polyethylenimine-functionalized TUD-1 mesoporous silica. AB - Samples of porous, foam-like TUD (Technische Universitat Delft)-1 mesoporous silica were functionalized with polyethylenimine and were used as a substrate for CO(2) adsorption. Produced solids were characterized by means of electron microscopy, thermogravimetric analysis, and N(2) adsorption/desorption at 77K, in order to prove that polymer chains efficiently filled the pores of functionalized samples. CO(2) adsorption isotherms on polyethylenimine-containing TUD-1 were evaluated at T=298, 313, 328, and 348 K for pressures up to 100 kPa by means of a volumetric technique. The CO(2) adsorption capacity proved to be significantly dependent on temperature, with the highest capacity encountered at T=348 K. The experimental data for CO(2) adsorption were satisfactorily described by means of the Langmuir isotherm, and the dependence of the isosteric heat on the fractional coverage of the adsorbent was evaluated by means of the van't Hoff equation, showing values in the order of 80 kJ/mol for a fractional coverage of about 50%. PMID- 22082800 TI - In situ synthesis of Pt/carbon nanofiber nanocomposites with enhanced electrocatalytic activity toward methanol oxidation. AB - Pt/carbon nanofiber (Pt/CNF) nanocomposites were facilely synthesized by the reduction of hexachloroplatinic acid (H(2)PtCl(6)) using formic acid (HCOOH) in aqueous solution containing electrospun carbon nanofibers at room temperature. The obtained Pt/CNF nanocomposites were characterized by TEM and EDX. The Pt nanoparticles could in situ grow on the surface of CNFs with small particle size, high loading density, and uniform dispersion by adjusting the concentration of H(2)PtCl(6) precursor. The electrocatalytic activities of the Pt/CNF nanocomposites were also studied. These Pt/CNF nanocomposites exhibited higher electrocatalytic activity toward methanol oxidation reaction compared with commercial E-TEK Pt/C catalyst. The results presented may offer a new approach to facilely synthesize direct methanol fuel cells (DMFCs) catalyst with enhanced electrocatalytic activity and low cost. PMID- 22082801 TI - An efficient route to aqueous phase synthesis of nanocrystalline gamma-Al2O3 with high porosity: from stable boehmite colloids to large pore mesoporous alumina. AB - In this paper we emphasise the important role of Pluronic F127 on the porosity of mesoporous alumina prepared from boehmite colloids. By focusing on the F127/boehmite interactions we show how the concepts of interface science may help to predict and improve the textural characteristics of mesoporous alumina. By varying the synthetic parameters, in particular the copolymer content, we show that the porosity of gamma-Al(2)O(3) can be enhanced by 400% and the average pore diameter can be expanded from 5 to 14 nm. These results are discussed in terms of interactions between the Pluronic F127 and boehmite colloids, and are correlated to the critical micelle concentration (CMC) of the copolymer. The textural characteristics of the mesoporous alumina can be further improved either by introducing hydrocarbons in the preformed boehmite/copolymer sols or by concentrating the sols. In comparison with as-synthesised alumina, those prepared with F127 showed improved thermal stability. Furthermore, boehmite/copolymer sols were stable for all surfactant concentrations investigated and can give high quality coatings suitable for catalytic applications. PMID- 22082802 TI - A novel orchid-like polyaniline superstructure by solvent-thermal method. AB - An orchid-like polyaniline (PANI) structures was synthesized by initialing the polymerization at 80 degrees C and growing at 25 degrees C using ethanol and water as co-solvent in the presence of toluene-p-sulfonic acid (p-TSA) as the dopant. The "flowers" are consisted of 8-14 pieces of "petals" with 5-8 MUm in length. By adjusting the molar ratio of p-TSA/aniline, the cooling rate and the component of the solvent, flake-like and peony-like morphology can also be obtained. The formation mechanism of the orchid-like structure is proposed. PMID- 22082803 TI - Interactions between beta-cyclodextrin and an amino acid-based anionic gemini surfactant derived from cysteine. AB - The interaction between beta-cyclodextrin (beta-CD) and an amino acid-based anionic gemini surfactant derived from cysteine (C(8)Cys)(2) was studied by three independent techniques: electrical conductivity, UV-Vis spectral displacement technique using phenolphthalein as probe, and (1)H NMR spectroscopy. The data obtained indicated the formation of a 1:1 inclusion complex between beta-CD and the gemini surfactant studied and allowed for the determination of the binding constant, K(1), by considering this stoichiometry. Electrical conductivity, spectral displacement technique, and NMR chemical shift measurements, obtained for aqueous beta-CD-surfactant systems, yielded consistent K(1) values in the order of 10(2) dm(3) mol(-1), typical of a weakly bound beta-CD-surfactant complex. The influence of the presence of the inclusion complex on the micellization process of the gemini surfactant has also been studied and the apparent critical micelle concentration (cmc(*)) has been obtained. Increasing beta-CD concentration was found to shift the cmc(*) to higher values, as complexed surfactant monomers are not available to form micelles and aggregation takes place only when all beta-CD cavities are occupied. PMID- 22082804 TI - Aberrant expressions of leptin and adiponectin receptor isoforms in chronic myeloid leukemia patients. AB - BACKGROUND: Leptin and adiponectin receptors mediate the role of leptin in stimulating the growth of leukemic cells and the protective function of adiponectin undertaken in several malignancies such as leukemia. In this study, we investigated the involvement of the expression of leptin and adiponectin receptors in chronic myeloid leukemia (CML) pathogenesis. METHODS: The expression of leptin receptor isoforms, OB-Rt, OB-Ra, and OB-Rb, and the expression of adiponectin receptors, AdipoR1 and AdipoR2, were measured as mRNA levels in two CML cell lines (K562 and Meg-01) and 20 CML patients and 24 healthy controls by using RT-PCR. RESULTS: OB-Rt and OB-Ra isoforms expression of the leptin receptors were found to be significantly lower in Meg-01 cell lines than K562 cells. All leptin receptors were downregulated in CML patients and more particularly OB-Rb level was found to be undetectably low in normal PBMC as well as in CML patients. AdipoR1 expression level was higher in Meg-01 than in K562, whereas AdipoR2 level was found to be unchanged in both cell lines. Interestingly, while AdipoR1 expression increased in CML patients, AdipoR2 decreased. Moreover, imatinib therapy did not affect both leptin and adiponectin isoform expressions. CONCLUSION: While the decrease in leptin receptor levels in CML patients was confirmed, the increase in AdipoR1 levels and relevant decrease in AdipoR2 levels depicted their possible involvement in CML pathogenesis. This suggests different functions of adiponectin receptors in CML development. PMID- 22082805 TI - Effects by anthrax toxins on hematopoiesis: a key role for cytokines as mediators. AB - An understanding of anthrax toxins on the emerging immune system and blood production are significant to medicine. This study examined the effects of anthrax toxin on hematopoiesis and determined roles for cytokines. Anthrax holotoxin toxin is three components: protective antigen (PA) binds to the target cell and mediates the entry of lethal factor (LF) and edema factor (EF). Anthrax toxin dramatically inhibits signaling in immune cells. We first identified the cell subsets that interacted with the protective antigen (PA) and then studied the effects on hematopoietic progenitors in clonogenic assays: granulocytic monocytic (CFU-GM) and late erythroid (CFU-E). Multi-color immunofluorescence with FITC-PA indicated its interaction with early and late myeloid cells. Clonogenic assays, in the presence or absence of holotoxin and individual toxin proteins resulted in significant suppression by hologenic toxic alone, despite the presence of growth-promoting cytokines. Antibodies to anthrax receptor (ATR1) reversed the suppressive effects, indicating specificity. Monomeric proteins showed different effects on myeloid and erythroid progenitors. Suppression was not due to cell death, based on undetectable active caspase 3. Cytokine array analyses with supernatants from toxin-stimulated stroma showed an increase in the hematopoietic suppressor, MIP-1alpha. This finding, in addition to our previous studies, showing an increase in IL-10, suggested indirect roles for cytokines in toxin-mediated hematopoietic suppression. The chemokine, SDF-1alpha was increased. Since SDF-1 is involved in the mobilization of hematopoietic cells, it is likely that anthrax holotoxin could induce cell exit from BM. In summary, anthrax holotoxin, but not individual toxins, exerted hematopoietic effects on myeloid and erythroid progenitors via specific receptor, partly through the induction of cytokines. PMID- 22082806 TI - Function and expression of renal epithelial sodium transporters in rats with thyroid dysfunction. AB - Thyroid disorders are accompanied by major changes in renal sodium handling and blood pressure. Sodium transporters play a crucial role in regulating sodium excretion. We determined the function and expression of type 3 Na/H (NHE3) exchanger, type 2 Na+K+2Cl co-transporter (NKCC2) co-transporter, NaCl co transporter (NCC) cotransporter, and epithelial sodium channel (ENaC) in hypoand hyperthyroid rats at 6 weeks after each thyroid disorder induction. We measured the renal response to functional blockade of the tubular sodium transporters, using acetazolamide to inhibit the activity of NHE3, furosemide for NKCC2, hydrochlorotiazide for NCC, and amiloride for ENaC. Expression of sodium transporters was analyzed by measuring the protein abundance by Western blot. The responsiveness to NHE3 inhibition and NHE3 protein was lower in hypothyroid rats and higher in hyperthyroid rats vs controls. Hypothyroid rats showed greater diuretic and natriuretic responses to NKCC2 and ENaC blockade and higher protein abundance of NKCC2 vs controls. Hyperthyroid rats showed greater protein expression of NKCC2 and NCC vs controls. Groups did not differ in responsiveness to NCC blockade. The expression and activity of ENaC were lower in hyperthyroid rats. In conclusion, reduced NHE3 activity may participate in the low blood pressure of hypothyroid rats and elevated NHE3 activity in the high blood pressure of hyperthyroid rats. These proximal alterations are counter-balanced by functional upregulation of NKCC2 and ENaC in downstream nephron segments of hypothyroid rats and by downregulation of alphaENaC activity and expression in hyperthyroid rats. PMID- 22082810 TI - Improvement of mitral valve coaptation with supraannular plication of the posterior annulus--a newly designed strip for posterior annular plication--. AB - PURPOSE: The aim of this study was to evaluate a newly-designed mitral annuloplasty strip (the Mitra-Lift((r)) strip) in patients undergoing mitral valve repair for mitral regurgitation (MR). METHODS: A total of 30 patients who underwent posterior mitral strip annuloplasty for moderately severe to severe MR were evaluated in this study. The strip annuloplasty (SA) consisted of the use of the newly-designed strip and the suture of the supra-annular atrial wall of 5.0 mm width and the posterior annulus. In addition to SA, six patients (20.0%) with tethered posterior leaflets required posterior leaflet augmentation. Improvement in MR and hemodynamic parameters of the valve with the fixed strip were assessed. RESULTS: After SA, all patients exhibited little or no MR, with no individual exhibiting signs of exacerbation during the follow-up period. A stable coaptation occurred below the strip and the posterior annulus due to forward movement and lifting of the posterior annulus without significant reduction of intercommissural dimension. During the cardiac cycle, the intercommissural dimensions showed considerable changes, which meant a dynamic motion of the anterior leaflet and the commissures. CONCLUSIONS: Formation of a stable leaflet coaptation was associated with a dynamic change of the intercommissural dimension during the cardiac cycle and resulted in a reliable, annuloplasty strip, representing a new concept in annuloplasty. PMID- 22082811 TI - Thoracoscopic segmentectomy with intraoperative evaluation of sentinel nodes for stage I non-small cell lung cancer. AB - OBJECTIVES: Segmentectomy is the treatment of choice for small-sized non-small cell lung cancer (NSCLC); however, it is difficult to decide the surgical procedure because accurate evaluation of hilar lymph node metastasis remains unclear. We here report the outcome of video-assisted thoracic surgery (VATS) segmentectomy with and without the assessment of sentinel nodes. MATERIALS AND METHODS: Eighty-three patients with stage IA NSCLC underwent VATS segmentectomy between January 2003 and December 2010. Twenty patients underwent indocyanine green fluorescence imaging for sentinel node biopsy (SNB) and 63 did not. Intraoperative real-time quantitative RT-PCR to determine the expression of CK-19 was used for evaluation of metastasis. Perioperative outcome, local recurrence rates and survival were compared in both groups. RESULTS: Sentinel lymph nodes were identified in 16 of 20 patients (80%) with segmentectomy in the SNB group. The false negative rate was 0%. By RT-PCR for CK-19 expression, only one of these patients showed positive sentinel nodes, which indicated isolated tumor cells; however, segmentectomy was not converted to lobectomy. Seven of 63 patients with VATS segementectomy without SNB and none of the SNB group relapsed. In the relapsed patients without SNB, 4 (6.3%) were local recurrences and 3 (4.7%) were distant metastases. Recurrence-free survival rates in both groups were not significantly different because of the short follow-up period of the SNB group. CONCLUSIONS: Our study demonstrated that VATS segmentectomy with SNB was useful for deciding intraoperatively to perform segmentectomy with an accurate lymph node status. PMID- 22082812 TI - Long-term results after the box pulmonary vein isolation procedure for chronic atrial fibrillation in mitral valve surgery. AB - BACKGROUND: We hypothesized that chronic atrial fibrillation (AF) originated from the pulmonary veins, and was maintained by irregular activations of the posterior left atrium. We had performed the box pulmonary vein isolation procedure for the elimination of chronic AF associated with solitary mitral valve disease from 1999 to 2004. This paper evaluated the long-term results of this procedure over more than 6 years, and discussed the role of the pulmonary veins and posterior left atrium in maintaining AF. METHODS: Fifty-three patients were examined after box pulmonary vein isolation procedure concomitant with solitary mitral valve surgery retrospectively. We divided the patients into two groups with or without the elimination of AF (AF group and non-AF group). The disappearance of AF was determined by electrocardiography, and atrial function was evaluated by transthoracic echocardiography. The elimination of chronic AF and the recovery of atrial systolic function after surgery were evaluated over more than 6 years of follow-up. RESULTS: In a total of 462.8 patient years of follow-up (range 6.3 to 11.5 years, mean: 8.9 +/- 2.7 years), AF disappeared in 77.3% of the patients (41/53) at 3 months and in 70.6% (36/51) of the patients at 6 years after the box pulmonary vein isolation, respectively. Among the preoperative variables, a long duration of AF and a large diameter of the left atrium were the predictive factors for recurrences of AF (p <0.05). There was no left atrial tachycardia even though we did not perform ablation towards the mitral valve annulus. CONCLUSIONS: The box pulmonary vein isolation procedure can terminate chronic AF associated with solitary mitral valve disease, and maintain a sinus rhythm for more than 6 years in 70% of chronic AF patients. This study implicates the pulmonary veins and posterior left atrium in maintaining chronic AF associated with mitral valve disease. PMID- 22082813 TI - Conact lens & anterior eye. PMID- 22082814 TI - Cardioprotective effect of apelin-13 on cardiac performance and remodeling in end stage heart failure. AB - BACKGROUND: Apelin and its cognate G protein-coupled receptor, APJ, constitute a signaling pathway with a positive inotropic effect on cardiac function. Recently, we and other investigators demonstrated that a reduction in myocardial apelin/APJ expression might play a critical role in experimental models of end-stage heart failure (HF). Therefore, we evaluated whether exogenous apelin infusion restores apelin/APJ expression and improves cardiac function in the failing heart of Dahl salt-sensitive hypertensive (DS) rats. METHODS AND RESULTS: High salt-loaded DS rats were treated with vehicle and pyroglutamylated apelin-13 (Pyr-AP13; 200ug.kg(-1).day(-1), IP) from the age of 11 to 18 weeks. Decreased end-systolic elastance and percent fractional shortening in failing rats was significantly ameliorated by Pyr-AP13. Pyr-AP13 effectively inhibited vascular lesion formation and suppressed expression of inflammation factors such as tumor necrosis factor alpha and interleukin-1beta protein. Downregulation of apelin and APJ expression, and phosphorylation of endothelial nitric oxide synthase at Ser(1177) and Akt at Ser(473) in failing rats was significantly increased by Pyr-AP13. Upregulation of NAD(P)H oxidase p22(phox), p47(phox), and gp91(phox) in DS rats was significantly suppressed by Pyr-AP13. CONCLUSIONS: Exogenous apelin-13 may ameliorate cardiac dysfunction and remodeling and restore apelin/APJ expression in DS rats with end stage HF. Thus, apelin-13 may have significant therapeutic potential for end stage HF. PMID- 22082815 TI - Routine depression assessment for patients with coronary artery disease. A new standard of care? PMID- 22082816 TI - Platelet inhibition and surgical bleeding. A plea for more science and evidence based guidelines. PMID- 22082817 TI - Renal protection from prolonged cold ischemia and warm reperfusion in hibernating squirrels. AB - BACKGROUND: We have previously shown that cold ischemia (CI) results in massive increases in caspase-3 activity, tubular apoptosis, and brush border injury (BBI) in mouse kidneys. During hibernation, the 13-lined ground squirrel (GS) cycles through repeated CI during torpor, followed by warm ischemia/reperfusion (WI) during interbout arousal (IBA). We sought to determine whether CI and WI during hibernation caused caspase-3 activation, tubular apoptosis, acute tubular necrosis, or BBI, and reduced renal function. We also determined whether protection was dependent on the stage of hibernation. METHODS: Radiotelemeters were implanted in 1-year-old GS, and core body temperature was remotely monitored. GS kidneys at various stages of hibernation were subjected to ex vivo CI. RESULTS: Tubular apoptosis was not detected and caspase-3-like activity was not different between hibernating and summer kidneys. Despite prolonged CI followed by WI and reperfusion, acute tubular necrosis and apoptosis did not occur in hibernating kidneys. BBI was absent in torpid kidneys but significantly increased in IBA kidneys and associated with an increase in caspase-3-like activity, suggesting that IBA kidneys are more susceptible to injury than summer or torpid kidneys. Renal function and urine concentrating ability diminished during torpor but returned during IBA. CONCLUSIONS: Despite BBI, IBA kidneys clear serum creatinine and concentrate urine. Kidneys from both summer and hibernating animals tolerated ex vivo CI, confirming that protection from apoptotic and necrotic cell death is independent of the stage of hibernation. An understanding of how renal protection occurs during hibernation may help in understanding the pathophysiology of delayed graft function. PMID- 22082818 TI - Temporal association between increased virus-specific Th17 response and spontaneous recovery from recurrent hepatitis C in a liver transplant recipient. AB - BACKGROUND: Spontaneous clearance of hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) is a rare occurrence. Here, we present detailed immunological analysis of an interferon naive OLT recipient receiving uninterrupted immunosuppression who cleared HCV spontaneously 2 years after transplantation. METHODS: Enzyme-linked immunospot assay analysis of peripheral T cell interferon gamma (IFN-gamma), interleukin (IL)-10, and IL-17 response to HCV core and nonstructural antigen 4 and enzyme-linked immunosorbent assay (ELISA) to collagen (Col) subtypes I, II, IV, and V were performed in the index patient at the time of viral clearance and compared with an OLT cohort with persistent viremia matched for time from OLT, immunosuppression, and histology. Enzyme linked immunospot assay and ELISA analysis were repeated on the patient 4 years after OLT. Transcription-mediated amplification assays were used to confirm viral clearance. RESULTS: Compared with a cohort of post-OLT and nontransplanted viremic HCV patients, the index patient with HCV clearance demonstrated higher IL 17, IL-10, and lower IFN-gamma response to nonstructural antigen 4 and core antigen and a higher titer of antibodies (Abs) to Col subtypes I, II, and V during clearance. On follow-up 2 years later, HCV-specific IFN-gamma was increased in the index patient, with a decline in IL-17 and IL-10 response and Col I, II, and V Ab titer. CONCLUSIONS: Virus-induced activation of Th-17 cells may contribute to HCV clearance post-OLT. Maintenance of viral suppression may be facilitated by restoration of Th1 (IFN-gamma) responses. Modulation of Th17 immunity deserves further attention as a therapeutic strategy in the treatment of HCV recurrence post-OLT. PMID- 22082819 TI - Tolerance to vascularized composite allografts in canine mixed hematopoietic chimeras. AB - BACKGROUND: Mixed donor-host chimerism, established through hematopoietic cell transplantation (HCT), is a reproducible strategy for the induction of tolerance toward solid organs. Here, we ask whether a nonmyeloablative conditioning regimen establishing mixed donor-host chimerism leads to tolerance of antigenic vascularized composite allografts. METHODS: Stable mixed chimerism was established in dogs given a sublethal dose (1-2 Gy) total body irradiation before and a short course of immunosuppression after dog leukocyte antigen-identical marrow transplantation. Vascularized composite allografts from marrow donors were performed after a median of 36 months (range, 4-54 months) after HCT. RESULTS: All marrow recipients maintained mixed donor-host hematopoietic chimerism and accepted vascularized composite allografts for periods ranging between 52 and 90 weeks; in turn, marrow donors rejected vascularized composite allografts from their respective marrow recipients within 18 to 29 days. Biopsies of muscle and skin of vascularized composite allografts from mixed chimeras showed few infiltrating cells compared with extensive infiltrates in biopsies of vascularized composite allografts from marrow donors. Elevated levels of CD3+ FoxP3+ T-regulatory cells were found in skin and muscle of vascularized composite allografts of mixed chimeras compared with normal tissues. In mixed chimeras, increased numbers of T-regulatory cells were found in draining compared with nondraining lymph nodes of vascularized composite allografts. CONCLUSIONS: These data suggest that nonmyeloablative HCT may form the basis for future clinical applications of solid organ transplantation and that T-regulatory cells may function toward maintenance of the vascularized composite allograft. PMID- 22082820 TI - Current status of hepatocyte transplantation. AB - Hepatocyte transplantation (HT) has been performed in patients with liver-based metabolic disease and acute liver failure as a potential alternative to liver transplantation. The results are encouraging in genetic liver conditions where HT can replace the missing enzyme or protein. However, there are limitations to the technique, which need to be overcome. Unused donor livers to isolate hepatocytes are in short supply and are often steatotic, although addition of N acetylcysteine improves the quality of the cells obtained. Hepatocytes are cryopreserved for later use and this is detrimental to metabolic function on thawing. There are improved cryopreservation protocols, but these need further refinement. Hepatocytes are usually infused into the hepatic portal vein with many cells rapidly cleared by the innate immune system, which needs to be prevented. It is difficult to detect engraftment of donor cells in the liver, and methods to track cells labeled with iron oxide magnetic resonance imaging contrast agents are being developed. Methods to increase cell engraftment based on portal embolization or irradiation of the liver are being assessed for clinical application. Encapsulation of hepatocytes allows cells to be transplanted intraperitoneally in acute liver failure with the advantage of avoiding immunosuppression. Alternative sources of hepatocytes, which could be derived from stem cells, are needed. Mesenchymal stem cells are currently being investigated particularly for their hepatotropic effects. Other sources of cells may be better if the potential for tumor formation can be avoided. With a greater supply of hepatocytes, wider use of HT and evaluation in different liver conditions should be possible. PMID- 22082822 TI - Ventilatory functions in cotton textile workers and the role of some inflammatory cytokines. AB - Exposure to cotton dust in industrial environments causes inflammation in the airways of the exposed workers. This may manifest as respiratory complaints and changes in the respiratory functions after work shift and in the baseline of their ventilatory functions. The study aimed to investigate the effect of occupational exposure to cotton dust on respiratory symptoms, ventilatory functions and pro-inflammatory cytokine levels (tumor necrosis factor alpha, interleukin 6 and interleukin 1beta). The study was conducted on 63 textile workers and 65 nonexposed subjects. Both groups were matched for age, socioeconomic status and smoking habit. The respirable dust measured in the workplace did not exceed the permissible values of the Egyptian law 1994. The bacterial counts detected were within the occupational exposure limits of the industrial settings. The results revealed that the percentage of respiratory symptoms was higher in textile workers. Respiratory complaints were chronic cough (33.2%), chronic bronchitis (39.7%) and dyspnea (23.8%) in textile workers compared to (6.2%, 6.2% and 1.5%), respectively, in controls. There was a marked reduction in the ventilatory functions (forced vital capacity and forced expiratory volume in 1 s) in the textile workers compared to the controls. The additive effect of smoking on the ventilatory functions was not apparent. The ventilatory functions of the workers were significantly positively correlated with the duration of exposure. The cytokines were insignificantly higher in the textile workers compared to their controls. The textile workers with respiratory complaints showed significant decline in ventilatory functions and elevation in the cytokine levels compared to the nonsymtomatizing workers with significant difference in interleukin 1beta and interleukin 6. In conclusion, the results supported the fact that exposure to cotton dust deteriorates ventilatory functions and elevates proinflammatory cytokine levels. Analysis of the release of cytokines can be used to evaluate the immune responses to organic dust-induced airway inflammation. PMID- 22082823 TI - Fatal methanol poisoning: features of liver histopathology. AB - Methanol poisoning has become a considerable problem in Iran. Liver can show some features of poisoning after methanol ingestion. Therefore, our concern was to examine liver tissue histopathology in fatal methanol poisoning cases in Iranian population. In this study, 44 cases of fatal methanol poisoning were identified in a year. The histological changes of the liver were reviewed. The most striking features of liver damage by light microscopy were micro-vesicular steatosis, macro-vesicular steatosis, focal hepatocyte necrosis, mild intra-hepatocyte bile stasis, feathery degeneration and hydropic degeneration. Blood and vitreous humor methanol concentrations were examined to confirm the proposed history of methanol poisoning. The majority of cases were men (86.36%). In conclusion, methanol poisoning can cause histological changes in liver tissues. Most importantly in cases with mean blood and vitreous humor methanol levels greater than 127 +/- 38.9 mg/dL more than one pathologic features were detected. PMID- 22082824 TI - Anti-inflammatory and antioxidant effects of infliximab in a rat model of intestinal ischemia/reperfusion injury. AB - The aim of this study was to investigate the possible protective effects of infliximab on oxidative stress, cell proliferation and apoptosis in the rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group comprised 10 animals. Sham group animals underwent laparotomy without I/R injury. I/R groups after undergoing laparotomy, 1 hour of superior mesenteric artery ligation occurred, which was followed by 1 hour of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered intravenously. All animals were killed at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no biochemical and histopathological changes have been reported regarding intestinal I/R injury in rats due to infliximab treatment. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased reduced superoxide dismutase and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Infliximab treatment significantly attenuated the severity of intestinal I/R injury, inhibiting I/R induced apoptosis, and cell proliferation. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects on the experimental intestinal I/R model of rats. PMID- 22082825 TI - Biochemical evidence on the potential role of organophosphates in hepatic glucose metabolism toward insulin resistance through inflammatory signaling and free radical pathways. AB - Several studies show that organophosphate pesticides exert several effects on glucose homeostasis. The current study investigates the influence of subchronic exposure to malathion (MT) on hepatic gluconeogenesis in relation to acetyl cholinesterase (AChE) inhibition, oxidative stress and inflammatory response in the rat. MT was administered by gavage at doses of 25, 50 and 100 mg/kg for 32 days. Fasting hyperglycemia was seen in line with an increased activity of hepatic phosphoenolpyruvate carboxykinase, glucose 6-phosphatase and tumor necrosis factor alpha. In addition to the impaired glucose tolerance and inhibition of AChE in a dose-dependent manner, there were significant increases in hepatic lipid peroxidation, carbonyl groups and 8-deoxyguanosine as the biomarkers of reactive oxygen species-mediated damage to lipid, protein and DNA, respectively. Altered quality of the liver in glucose production especially gluconeogenesis could be a compensatory mechanism against MT toxicity or even result in tissue damage. MT-induced insulin resistance in the liver occurs through oxidative and inflammatory signaling pathways. PMID- 22082826 TI - Heat stress decreases testicular germ cell proliferation and increases apoptosis in short term: an immunohistochemical and ultrastructural study. AB - Scrotal hyperthermia has been known as a cause of male infertility but the exact mechanism leading to impaired spermatogenesis is unknown. This work was aimed to investigate the role of scrotal hyperthermia on cell proliferation and apoptosis in testes. The rats were randomly allotted into one of the four experimental groups: A (control), B (1 day after scrotal hyperthermia), C (14 days after scrotal hyperthermia), and D (35 days after scrotal hyperthermia); each group comprised 7 animals. Scrotal hyperthermia was carried out in a thermostatically controlled water bath at 43 degrees C for 30 min once daily for 6 consecutive days. Control rats were treated in the same way, except the testes were immersed in a water bath maintained at 22 degrees C. Hyperthermia-exposed rats were killed under 50 mg/kg ketamine anaesthesia and tissue samples were obtained for biochemical and histopathological investigations. Hyperthermia treatment significantly decreased the testicular antioxidant system, including decreases in the glutathione level, superoxide dismutase, and glutathione peroxidase activities. Moreover, exposure to hyperthermia resulted in lipid peroxidation increase in testes. Our data indicate a significant reduction in the expression of proliferating cell nuclear antigen and an enhancement in the activity of terminal deoxynucleotidyl transferase dUTP nick end labelling after scrotal hyperthermia. In scrotal hyperthermia, the mitochondrial degeneration, dilatation of smooth endoplasmic reticulum, and enlarged intercellular spaces were observed in both Sertoli and spermatid cells. Scrotal hyperthermia is one of the major factors that impair spermatogenesis in testis. This heat stress is shown to be closely associated with oxidative stress, followed by apoptosis of germ cells. PMID- 22082827 TI - Tissues distribution of heavy metals and erythrocytes antioxidant status in rats exposed to Nigerian bonny light crude oil. AB - The harmful effects of folkloric uses of Nigerian bonny light crude oil (BLCO) in ailments management may outweigh the expected beneficial effects. We investigated the levels of heavy metal concentrations in the tissues as well as the effect of BLCO on the antioxidant status of erythrocytes of rats after oral exposure to 0, 200 and 800 mg/kg BLCO for 7 days. Analysis of heavy metal concentrations in BLCO showed that Zn > Fe > Pb > Cu > Ni. The trend of accumulation of the metals in the tissues is blood-Fe > Pb >Zn whereas Cu and Ni levels were not affected; Liver-Ni > Zn > Fe > Cu > Pb and Testes-Ni > Cu > Pb > Zn > Fe. The order of concentration of the metals in the tissues is as follows: iron-blood > liver > testes; zinc-liver > blood > testes; lead-blood > liver > testes; copper-testes > liver > blood; nickel-liver > testes > blood. Activities of the antioxidant enzymes of erythrocytes such as superoxide dismutase, catalase, glutathione S transferase and glutathione peroxidase increased significantly in a dose dependent manner with significant elevation in hydrogen peroxide and malondialdehyde levels, whereas glutathione level was not significantly decreased in BLCO-treated animals. Collectively, the results showed that BLCO induces oxidative damage to erythrocytes of rats. PMID- 22082828 TI - Aspergillus hazardous problem in ceramic workers. AB - Ceramic workers are at a high risk of developing respiratory problems as they are exposed to high levels of respirable dust containing silica and high microbial counts, including high Aspergillus counts. The aim of the study was to study the percentage of ceramic workers with positive Aspergillus (A.) through polymerase chain reaction (PCR) and specific IgE (sIgE) for the different Aspergillus species. PCR and specific IgE (sIgE) for the different Aspergillus species (A. flavus, A. fumigatus and A. niger) were estimated in 40 ceramic workers and 56 control subjects. Results revealed that 32.5% of the workers' sputum was PCR positive for Aspergillus. About 69.2% of them were A. flavus positive, 15.4% A. niger positive, 7.7% A. fumigatus positive and 7.7% A. flavus and A. fumigatus positive. The percentage change in sIgE for A. fumigatus between the workers and their controls was over 100%, while less than 50% for the other two species. The sIgE levels for the three Aspergillus species were not significantly correlated with the duration of exposure. Fungal exposure could be considered potential hazardous problem in ceramic industry. There were no significant correlations between the duration of exposure and the sIgE for the different Aspergillus species. PMID- 22082829 TI - Effect of fenugreek seed extract on adriamycin-induced hepatotoxicity and oxidative stress in albino rats. AB - The purpose of this work was to evaluate the effect of aqueous extract of fenugreek seeds against hepatotoxicity induced in albino rats by the anticancer drug adriamycin (ADR). Animals were given single dose of ADR (10 mg/kg body weight) and were killed after 2 and 4 weeks. Liver of ADR-treated animals showed histopathological and biochemical alterations. The histopathological changes include hepatic tissue impairment, cytoplasmic vacuolization of the hepatocytes, congestion of blood vessels, leucocytic infiltrations and fatty infiltration. Moreover, the expression of proliferating cell nuclear antigen was increased in ADR-treated rats. The liver enzymes, aspartate aminotransferase (ALT) and alanine aminotransferase (AST) were increased in the sera of treated rats. Moreover, ADR significantly increased the concentration of malondialdehyde (MDA) and decreased the activities of superoxide dismutase (SOD) and catalase (CAT) in hepatic tissue. Treating animals with ADR and aqueous extract of fenugreek (0.4 g/kg body weight) seeds led to an improvement in histological and biochemical alterations induced by ADR. The biochemical results showed that AST and ALT appeared normal together with reduction in the level of MDA (lipid peroxidation marker) and increase in SOD and CAT activities. It was concluded from this study that the aqueous extract fenugreek seeds has a beneficial impact on ADR-induced hepatotoxicity due to its antioxidant effect in albino rats. PMID- 22082830 TI - Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential. AB - Parkin is a multifunctional protein, including maintaining mitochondrial homeostasis. Recent evidence suggests that Parkin is recruited from the cytoplasm to damaged mitochondria with low membrane potential. We found that intracellular localization of Parkin changed with cellular growth phase. Parkin was preferentially localized in the mitochondria of cultured cells. The mitochondria with large amounts of Parkin showed preserved membrane potentials even during treatment with carbonyl cyanide m-chlorophenylhydrazone. Here we report a novel protein named Klokin 1 that transports Parkin to the mitochondria. Klokin 1 was localized to the mitochondria and enhanced mitochondrial expression of Parkin. Klokin 1 enhanced cell viability in Parkin-silenced cells. Klokin 1 expression was enhanced in the brains of Parkin-deficient mice but not in an autopsied PARK2 brain. Our findings indicate that mitochondrial Parkin prevents mitochondrial depolarization and that Klokin 1 may compensate for Parkin deficiency. PMID- 22082831 TI - Targeted mutation of SLC4A5 induces arterial hypertension and renal metabolic acidosis. AB - The human SLC4A5 gene has been identified as a hypertension susceptibility gene based on the association of single nucleotide polymorphisms with blood pressure (BP) levels and hypertension status. The biochemical basis of this association is unknown particularly since no single gene variant was linked to hypertension in humans. SLC4A5 (NBCe2, NBC4) is expressed in the collecting duct of the kidney and acts as an electrogenic ion-transporter that transports sodium and bicarbonate with a 1:2 or 1:3 stoichiometry allowing bicarbonate reabsorption with relatively minor concurrent sodium uptake. We have mutated the Slc4a5 gene in mice, which caused a persistent increase in systolic and diastolic BP. Slc4a5 mutant mice also displayed a compensated metabolic acidosis and hyporeninemic hypoaldosteronism. Analysis of kidney physiology revealed elevated fluid intake and urine excretion and increased glomerular filtration rate. Transcriptome analysis uncovers possible compensatory mechanisms induced by SLC4A5 mutation, including upregulation of SLC4A7 and pendrin as well as molecular mechanisms associated with hypertension. Induction of metabolic alkalosis eliminated the BP difference between wild-type and Slc4a5 mutant mice. We conclude that the impairment of the function of SLC4A5 favors development of a hypertensive state. We reason that the loss of sodium-sparing bicarbonate reabsorption by SLC4A5 initiates a regulatory cascade consisting of compensatory bicarbonate reabsorption via other sodium-bicarbonate transporters (e.g. SLC4A7) at the expense of an increased sodium uptake. This will ultimately raise BP and cause hypoaldosteronism, thus providing a mechanistic explanation for the linkage of the SLC4A5 locus to hypertension in humans. PMID- 22082833 TI - Cause of death for those with diabetes and/or cancer provides further support for an important role of vitamin D in reducing risk of many types of disease. PMID- 22082834 TI - Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl) 2-[4-(substituted) benzylidene]-hydrazinecarbothio amides. AB - Thirty six new N-(4-substituted phenyl)-2-[4-(substituted) benzylidene] hydrazinecarbothioamides were synthesized and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity was established in three seizure models i.e. MES, scMET and 6 Hz model. The most active compound was 2-[4 (4-chlorophenoxy)benzylidene]-N-(4-fluorophenyl)hydrazinecarbothioamide PC 31 which showed 100% protection at 0.5 h in the 6 Hz test. Compound 2-[4-(4 bromophenoxy) benzylidene]-N-(4-bromophenyl) hydrazinecarbothioamide PC 23 was found to be active in both the MES and 6 Hz test. A computational study was carried out from calculation of a pharmacophore pattern and the prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in the Lamarckian genetic algorithm based on flexible docking studies. PMID- 22082832 TI - Hyperpolarizing GABAergic transmission depends on KCC2 function and membrane potential. AB - KCC2 comprises the major Cl(-) extruding mechanism in most adult neurons. Hyperpolarizing GABAergic transmission depends on KCC2 function. We recently demonstrated that glutamate reduces KCC2 function by a phosphorylation-dependent mechanism that leads to excitatory GABA responses. Here we investigated the methods by which to estimate changes in E(GABA), as well as the processes that lead to depolarizing GABA responses and their effects on neuronal excitability. We demonstrated that current-clamp recordings of membrane potential responses to GABA can determine upper and lower limits of E(GABA). We also further characterized depolarizing GABA responses, which both excited and inhibited neurons. Our analyses revealed that persistently active GABA(A) receptors contributed to loading Cl(-) during the glutamate exposure, indicating that tonic inhibition can facilitate the development of depolarizing GABA responses and increase excitability after pathophysiological insults. Finally, we demonstrated that hyperpolarizing GABA responses could temporarily switch to depolarizing responses when they coincided with an afterhyperpolarization. PMID- 22082835 TI - Immunological similarity of thyroid stimulating antibody (TSAb) and thyroid blocking antibody (TBAb) with animal IgG. AB - Previously we reported neutralization and partial purification of TSAb and TBAb activity using heterophilic antibody (Ab) to animal IgG from Graves' disease. Thus, we examined immunological similarity of TSAb and TBAb with animal IgG using experimentally generated anti-animal IgG [dog (d), bovine (b), porcine (p) and rabbit (rb)] Abs. TBII activity of TSAb- and TBAb-positive serum was neutralized by these anti-animal IgG Abs. Applied TSAb- or TBAb-IgG protein (purified by Protein A) on these anti-animal IgG Abs-bound column was found mainly in the unbound fraction (UF) (>65%) and partially in the bound fraction(BF) (<35%). The TBII and TSAb activity of TSAb-IgG in the BF showed significantly higher than the UF. Thus, the ratio of TBII activity (U/L)/mg protein in the BF/UF was high. TBII activity of TBAb-IgG was similarly purified by this column. We examined immunological characteristics of TSAb-and TBAb-Fab or F(ab')2 using rabbit anti bF(ab')2 Ab. TBII and TSAb activity of TSAb-Fab or- F(ab')2 and TBII activity of TBAb-Fab or -F(ab')2 were neutralized by anti-bF(ab')2 Ab. Partial purification of TSAb- or TBAb-Fab and -F(ab')2 by anti-bF(ab')2 Ab-bound column was also possible. Immunological similarity of TSAb- and TBAb-IgG with animal IgG such as d, b, p, rb by anti-animal IgG Ab, and TSAb- or TBAb-Fab and -F(ab')2 with bFab by anti-bF(ab')2 Ab were demonstrated. These fact suggest that both Fab and Fc portion of TSAb- and TBAb-IgG molecule have immunological similarity with animal IgG. PMID- 22082836 TI - Neutralization and purification of thyroid stimulating antibody (TSAb) and thyroid blocking antibody (TBAb) by heterophilic antibody to animal IgG in Graves' disease. AB - There are several reports that sera from Graves' patients contain heterophilic antibody (Ab) to animal IgG such as human anti-mouse antibody (HAMA). We examined the binding of TSAb and TBAb with heterophilic Ab. The binding of animal IgG with patient's IgG was examined by the inhibition of animal IgG on the binding of labeled bovine (b) IgG with patient's IgG. The binding to labeled bIgG was detected in the serum of 5 patients (2.7 %) among 185 patients with Graves' disease. The binding of the labeled bIgG with patient's IgG was inhibited by animal serum or the crude IgG (45% ammonium sulfate fraction of serum)(such as dog, horse, bovine, porcine, goat, ovine, rabbit, guinea-pig, rat, mouse) except human, monkey and chick. This heterophilic Ab which had cross reaction with mammalian IgG (except human, monkey) was used as human anti-animal IgG Ab. TBII and TSAb activity of TSAb-positive serum, and TBII activity of TBAb positive serum were neutralized by incubation with this Ab-bound column. Partial purification of TSAb- or TBAb- IgG from Protein A-purified TSAb- or TBAb-IgG was possible using this Ab-bound column. TBII and TSAb activity of TSAb-IgG and TBII activity of TBAb-IgG were neutralized by incubation with rabbit anti-human (h) IgG Ab (having cross-reaction with animal IgG). Further purification of Protein A-purified TSAb-IgG or TBAb-IgG by rabbit anti-hIgG Ab-bound column was impossible. The binding of TSAb and TBAb with heterophlic Ab means that TSAb-and TBAb-specific IgG have immunological similarity with mammalian species IgG compared to human IgG. PMID- 22082837 TI - Association between Leapfrog safe practices score and hospital mortality in major surgery. AB - BACKGROUND: The Leapfrog Group reports on hospitals' adoption of the National Quality Forum Patient Safety Practices. However, it is unknown whether hospital compliance with these safe practices is associated with improved outcomes in patients undergoing major surgery. METHODS: We analyzed the association between hospital mortality and Leapfrog Safe Practices among patients undergoing coronary artery bypass graft surgery (n=18,565), abdominal aortic aneurysm repair (n=2777), and hip replacement (n=25,067) in hospitals participating in the 2007 Leapfrog Hospital Survey using logistic regression. RESULTS: After adjusting for patient and hospital factors, we found that the total safety score (adjusted odds ratio: 1.000, 95% confidence interval: 0.999-1.001) was not associated with hospital mortality. Computerized physician order entry and ICU physician staffing were also not associated with hospital mortality. CONCLUSIONS: We did not find evidence that patients undergoing major surgery at hospitals which scored higher on the Leapfrog Safe Practices Survey had lower mortality rates. The Leapfrog safe practices score as a standalone quality measure may have limited power to distinguish between high-quality and low-quality hospitals. PMID- 22082838 TI - Spitz nevi and other Spitzoid lesions part I. Background and diagnoses. AB - Spitz nevi are melanocytic proliferations that are characterized by spindled and/or epithelioid nevomelanocytes. First interpreted as juvenile melanoma, these lesions were later characterized as benign and were observed to affect all age groups. Today, contrasting opinions persist regarding the fundamental benignancy versus malignancy within the spectrum of Spitz tumors. Beyond clinical outcome, this controversy has also been fueled by complex and sometimes convoluted classification schemes based on pathologic characteristics. More recently, immunophenotypic and molecular analyses have begun to clarify the etiologic nature of these tumors. Recent evidence suggests that histopathologic features that suggest more aggressiveness in Spitz tumors relate to mitoses and inflammation. PMID- 22082840 TI - Alopecia areata incognita. PMID- 22082839 TI - Spitz nevi and other Spitzoid lesions part II. Natural history and management. AB - For dermatologists, evidence-based management guidelines for Spitz tumors have not been established. Despite the lack of a standardized approach, most dermatologists recommend the excision of Spitz tumors occurring in adults and adopt more conservative measures towards pediatric cases. The histopathologic attributes and the clinical scenario are factored into management in each case. While the metastatic behavior of certain Spitz tumors is well known, the malignant potential of these lesions remains unclear because they only rarely result in negative outcomes. The risks and benefits of adjunctive measures, such as sentinel lymph node biopsy and interferon use, remain untested and are subjects of ongoing controversy. (In part II of this continuing medical education article, we will continue to use the terminology defined in part I for purposes of continuity. "Spitz tumor" is used as the umbrella term for the entire category of lesions, "common Spitz nevi" refers to only the most typical lesions seen in pediatric cases, and "atypical Spitz tumors" encompass the "all other" category, which continues to cause debate.). PMID- 22082841 TI - Skin carcinogenesis and driving. PMID- 22082842 TI - Statins differ significantly in their anti-inflammatory activity. PMID- 22082843 TI - Left-sided skin cancers on the arm from driving? Past and future lessons from Australia. PMID- 22082845 TI - Antibiotic susceptibility of Corynebacterium minutissimum isolated from lesions of Turkish patients with erythrasma. PMID- 22082846 TI - A randomized controlled crossover trial: lidocaine injected at a 90-degree angle causes less pain than lidocaine injected at a 45-degree angle. PMID- 22082847 TI - The AC Rule for melanoma: a simpler tool for the wider community. PMID- 22082848 TI - Actinomycosis presenting as a destructive ulcerated plaque on the palate and gingiva. PMID- 22082849 TI - Gemcitabine-associated sweet syndrome-like eruption. PMID- 22082850 TI - Zoledronic acid-induced cutaneous B-cell pseudolymphoma. PMID- 22082853 TI - Mechanical fatigue cycling on teeth restored with fiber posts: impact of coronal grooves and diameter of glass fiber post on fracture resistance. AB - AIM: The aim of this paper was to evaluate the effect of different diameters and surface characteristics of a glass fiber post on the fracture resistance of teeth restored with fiber posts. METHODS: Eighty single-rooted bovine teeth were prepared, embedded in a PVC cylinder using acrylic resin, and allocated into 8 groups (N.=10) according to post diameter and shape: (smooth double-tapered fiber post) G1, G2, G3, and G4 with cervical diameters of 1.4 mm, 1.6 mm, 1.8 mm, and 2 mm, respectively; (double-tapered fiber posts with coronal grooves) G5, G6, G7, and G8 with cervical diameters of 1.4 mm, 1.6 mm, 1.8 mm, and 2 mm, respectively. A self-adhesive cement was used for post cementation, and the core build-up was standardized and made with composite resin. Specimens were stored for 7 days and then submitted to the mechanical fatigue testing (load=50 N., angle= 45 degrees , frequency=1 Hz, temperature=37 +/- 1 degrees C, number of cycles=1000000); the specimens that survived were submitted to static resistance testing (1 mm/min, 45 degrees ). The fracture loads and fracture modes was recorded. Data were submitted to 2-way ANOVA, post-hoc Tukey test and Pearson Correlation analysis. RESULTS: The cervical diameter of the post (P<0.0001) and surface characteristics (P=0.01013) significantly affected the fracture resistance (2-way ANOVA). Grooves reduced the fracture resistance when post diameter was 1.4 mm (G1 and G5). A moderate positive correlation was found between the fracture resistance and the fiber post diameter (r2=0.4445; P<0.0001) (Pearson correlation test). CONCLUSION: It appears that there is a direct relation between the diameter of the fiber post and the fracture strength of roots restored with fiber posts. But other factors may have influenced the fracture strength such as the reduction of intracanal dentin by the preparation for placement of wider fiber posts, since no difference was found for smooth fiber posts with different diameter. Otherwise, grooves at coronal part of the fiber post can damage the fracture resistance. PMID- 22082854 TI - Antimicrobial prescribing practice by dentists: a study from two primary care centres in UK. AB - AIM: Antimicrobials are often prescribed by dental practitioners for various dental conditions. However, non-adherence to standard prescribing guidelines is common in day to day dental practice. The aim of this paper was to investigate the types of antimicrobials used for various orofacial infections by primary care dental practitioners and to verify their adherence to standard prescribing guidelines. METHODS: Clinical data was analyzed from random electronic files of patients for whom antimicrobials were prescribed at two Dental Practices in UK between January 2009 and December 2010. British National Formulary (60th Edn), guidelines of Scottish Dental Clinical Effectiveness Programme and UK National Institute for Health and Clinical Excellence (NICE) Guidelines were used to identify adherence to prescribing guidelines. RESULTS: A total of 200 cases were analyzed. Amoxicillin (52%) was the commonest antimicrobial prescribed followed by metronidazole (43.5%). Mean age of the patients was 37.2 (+/- 15.1) years. Mean duration of antimicrobial prescription was for 4.3 (+/- 1.4) days. Non adherence to the standard prescribing guidelines was observed in 116 (58%) prescriptions. CONCLUSION: Amoxicillin continues to be the commonest antimicrobial preferred by primary care dental practitioners. Non-adherence to standard antimicrobial prescribing guidelines still remains high among primary care dentists. PMID- 22082855 TI - Comparison between two methods to evaluate temperature changes produced by composite light curing units and polymerization techniques. AB - AIM: This study evaluated the temperature change into the pulp chamber during the light curing of composite resin by direct (bovine tooth) and indirect (matrix) methods. METHODS: Direct method: fifty standardized cavities (2x2x2 mm) were prepared in bovine incisors, which were randomly assigned to evaluation of the temperature changes in the pulp chamber. Indirect method: temperature changes were evaluated through a dentine slice of 1.0 mm thickness in a elastomer cubic mold (2x2x2 mm). Filtek Z250 composite resin (3M/ESPE) was photo-activated using three light curing units: quartz-tungsten-halogen (QTH) by continuous, soft-start or intermittent light modulations; light emitting diode (LED); and plasma arc curing (PAC). Ten groups (N.=10) were established according to technique evaluation and photo-activation methods. All experiments were carried out in a controlled environment (37 degrees C and 50 +/- 10% relative humidity). The temperature changes were recorded using a digital thermometer attached to a type K thermocouple in contact with the dentin slice (indirect method) or in contact with the axial wall (dentin) of pulp chamber (direct method). The results were submitted to ANOVA and Tukey's test (alpha=0.05). RESULTS: Temperature changes were statistically higher for the matrix indirect method (2.56 oC) than bovine teeth direct method (1.17oC). The change temperature was statistically higher for the PAC (1.77 oC) when compared to other photo-activation modes in bovine teeth direct method. CONCLUSION: The two methods of temperature evaluation were different, however indirect method detected the higher temperature increase. Higher energy density arising from the light curing units and polymerization techniques promoted higher temperature increase. PMID- 22082856 TI - A consensus conference on management of the lower third molar. Italian Society of Odontostomatological Surgery. AB - During the first Congress of the Italian University Schools of Oral Surgery, held in Rome on 18-20th February, 2010, a task force was convened by the Italian Society of Odontostomatological Surgery (SIdCO) to summarize the data collected from the current literature on selected aspects relating to the mandibular third molar and its removal. The task of the Conference Participants was to review and analyze the pertinent literature and to elaborate conclusive recommendations for the management of the lower third molar. The statements made and the recommendations presented represent the consensus of the Conference, which can be considered the official statement of the SIdCO. PMID- 22082857 TI - Pit and fissure sealants: review of literature and application technique. AB - Molars and premolars are the most vulnerable teeth to caries attack. The high susceptibility of these teeth to caries is directly related to morphology of their occlusal surface that prevents both chemical cleaning by saliva and mechanical cleaning by toothbrush. Pit and fissures are therefore the most prone areas to caries and need special protection to prevent carious lesions. Fluoride is the only chemical element used for caries prevention. In fact, it favors the remineralisation of initial lesions, prevents the production of polysaccharides essential for the development and sustainment of bacterial plaque, and the absorption of salivary glycoprotein. Fluoride also reinforces enamel, making it less susceptible to caries. Two methods of fluoroprophylaxis have been proposed: the first is the systemic fluoroprophylaxis which is particularly efficient in preventing interproximal caries, but it does not form an adequate protective barrier on the occlusal surfaces; the other is the topical application of a fluoride gel to the tooth surface, although this second method does not significantly reduce the incidence of caries. The efficacy of the sealing procedures depends on the correct application technique. Observing an operative protocol will ensure a longer lasting retention of the sealant on the occlusal surface and subsequently prolongs the protection against caries. PMID- 22082858 TI - The controversial issue of centric relation: a historical and current dental perspective? AB - Human mandible is related to the anatomic skull in several positions among these; centric relation is a significant spatial position. It contributes not only as a reference position to build optimal occlusion in artificial dentition, but is also related to sound periodontal health and stomatognatic function. The purpose of this article is to critically discuss the historical and current definitions of centric relation, the different methods used for recording the same and its clinical implication in the restorative dental practice. PMID- 22082859 TI - Two-flap palatoplasty for treatment of oronasal fistula by trauma sequel. AB - The oronasal fistula is a chronic communication between the oral and nasal cavity that often affects patients with cleft palate. However, others uncommon causes of oronasal fistula are associated with facial traumas, infections and neoplasias. In this report we present a case of oronasal fistula as consequence of facial trauma that was treated by two flaps technique for palatoplasty. In this sense, we discussed treatment indications, surgical technique and patient prognostic of a relatively simple option that can provide a definitive repair with minimal morbidity. PMID- 22082860 TI - The reading man flap for closure of large meningomyelocele defects. AB - BACKGROUND: Closure of the skin defect in myelomeningocele repair is an essential step that determines the quality of the surgical result. In large myelomeningoceles, however, adequate skin coverage may not be accomplished by direct closure or skin undermining. In such cases, the skin defect is best repaired using flaps. The aim of this study is to evaluate the reading man procedure for closure of large meningomyelocele defect. METHODS: In this procedure, after neurosurgical repair and closure of the placode, the defect surgically becomes a circle in shape. Then, the circular defect is closed by transposition of two skin flaps designed in an unequal Z-plasty manner. Over 5 years, the reading man procedure was used for closure of large meningomyelocele defects in seven patients (four females and three males), aged between 1.5 and 6 months. The defect size was 10.5*7.25 cm (8.5*5.3 and 12.6*9.5 cm) on average. The localisation of the lesions was thoracolumbar in two patients and lumbosacral in five patients. RESULTS: In all patients, a successful tension-free one-stage closure was obtained without dog-ear formation. Except for one patient with minimal tip necrosis, healing was uneventful without any complications. There was no patient with late breakdown of the wound during 1.5 years (8 months-4 years) of mean follow-up. CONCLUSIONS: The reading man procedure enables the surgeon to achieve a tension-free defect closure of considerably large meningomyeleocele defects. Using two well-vascularised fasciocutaneous flaps, it provides a durable coverage and soft tissue padding over the neural tissues with no suture seam at midline. With these advantages, the Reading Man Procedure seems to be a useful and safe alternative for closure of large meningomyelocele defects. PMID- 22082861 TI - A transthyroidal method for arytenoid adduction: a basic anatomical study. AB - INTRODUCTION: Arytenoid adduction is a very effective procedure for medializing the posterior part of the vocal fold in vocal fold paralysis. Major drawback of the method is the technically sometimes-difficult access to the arytenoid with increased postoperative morbidity. Aim of this study was to provide basic anatomical data regarding the accessibility of the arytenoid cartilage through a thyroplasty window. Furthermore, to investigate the feasibility of an arytenoid adduction by fixation of a surgical screw to the arytenoid cartilage by using this approach. MATERIALS AND METHODS: 10 cadaver larynges, six female and four male, were dissected and measured for our points of interest. A standard manufacture-made surgical screw attached to a suture was anchored to the fovea oblonga of the arytenoid cartilage. RESULTS: Our anatomical measurements proved a mean distance from the posterior edge of the thyroid window to the arytenoid of about 8-9 mm in male larynges and 7-8 mm in female larynges. The distances did not differ significantly between the sexes. Pulling the anchored surgical screw medializes the posterior part of the vocal fold. DISCUSSION: Our data showed that there is a very constant morphometric relation between the thyroplasty window and the arytenoid cartilage. It is known that gender-related differences result in a veritable laryngeal dimorphism in nearly all absolute laryngeal dimensions. These differences appear to a much lesser extend in the distances from the surface to the depth, as was confirmed in our series. Using these findings led us to identification of the fovea oblonga near the muscular process as the most favorable point for fixation of a surgical screw through a conventional thyroplasty window. Pulling the attached suture medializes the arytenoid cartilage. PMID- 22082862 TI - The effect of experience on classification of voice quality. AB - OBJECTIVES/HYPOTHESIS: The purpose of this study was to compare the agreement among several groups of listeners with different types of experience in regard to classifying voice quality. STUDY DESIGN: This is a retrospective cross-sectional quasi-experimental design. METHOD: This study compared three groups: speech language pathologists who specialize in voice, singing voice teachers, and inexperienced listeners. All groups were asked to classify voice samples as breathy, rough, or normal. RESULTS: Results show a significant difference across all groups with speech-language pathologists demonstrating a substantial interrater agreement, kappa=0.67, z=103.07 (P<0.01); singing voice teachers demonstrating a moderate interrater agreement, kappa=0.53, z=79.10 (P<0.01); and inexperienced listeners demonstrating a fair interrater agreement, kappa=0.24, z=35.82 (P<0.01). CONCLUSIONS: Experienced listeners demonstrated a higher interrater agreement as compared with inexperienced listeners, with speech language pathologists demonstrating a superior agreement as compared with all groups. PMID- 22082863 TI - Laryngeal manifestations of relapsing polychondritis and a novel treatment option. AB - OBJECTIVES: Laryngotracheal involvement in relapsing polychondritis (RP) is rare. However, it is one of the most common causes of death in this patient population. We present three patients who primarily presented with laryngeal manifestations of RP and a novel treatment option for bamboo nodules. STUDY DESIGN: Retrospective chart review and comprehensive review of the literature. RESULTS: Two patients first presented to an otolaryngologist because of hoarseness and chronic cough that eventually progressed to dyspnea upon exertion. Laryngeal examination revealed subglottic stenoses. Upon rheumatologic workup both were diagnosed with RP. After treatment with steroids and immunosuppressive drugs, one of the patient's laryngeal symptoms improved, whereas the other required dilation procedures. Neither patient had classic auricular or nasal symptoms upon initial presentation. The third patient was being treated for spasmodic dysphonia and was noted to have bamboo nodules with accompanying dysphonia. Rheumatologic workup revealed RP and systemic treatment ensued. Unfortunately, her symptoms of hoarseness persisted despite systemic treatment. A pulsed-potassium-titanyl phosphate (KTP) laser was applied to the bilateral bamboo nodules, which eventually caused resolution of her vocal fold lesions and dysphonia. CONCLUSIONS: We present three patients with RP, all of whom sought health care by an otolaryngologist primarily. Awareness of this disease entity and the possibility for early laryngeal involvement is crucial for proper care of those with this life-threatening disease. PMID- 22082864 TI - Resolution of vocal fold polyps with conservative treatment. AB - OBJECTIVES: Vocal fold polyp is generally thought to require surgical removal. However, a certain proportion of polyps resolve with conservative treatment. This study was performed to clarify the frequency of spontaneous resolution of vocal fold polyp and identify features associated with polyps that are likely to resolve without surgery. STUDY DESIGN: Retrospective study. METHODS: A review of the medical records of patients diagnosed with vocal fold polyps in Tokyo Voice Center from January 2001 to December 2008. RESULTS: Of 644 patients with the diagnosis of vocal fold polyp, 132 received conservative treatment, 433 were treated surgically, and 79 dropped out without attending for further consultation after the initial visit. Of those treated conservatively, 55 experienced complete resolution after a mean of 5.1 months of follow-up from the outset, and 29 showed lesion shrinkage after a mean of 4.1 months of follow-up. Polyps that resolved with conservative therapy were more likely than those that remained unchanged or enlarged to occur in women, be smaller, and have a shorter duration of symptoms. We could not determine the superiority of voice therapy. CONCLUSIONS: At least 9.7% of vocal fold polyps might resolve without surgery. Conservative treatment should be considered as an option for selected patients with smaller and more recent-onset polyps. PMID- 22082865 TI - Glottal contact quotient in Mediterranean tongue trill. AB - OBJECTIVE: To determine the effect of a Mediterranean tongue trill (Zalghouta) on estimated glottal closed quotient (CQ). MATERIAL AND METHOD: A total of 10 female subjects participated in this study. Vocal fold CQ was measured for both sustained vowel [a] and the tongue trill named Zlaghouta using electroglottography. Frequencies and means (+/-standard deviation) were used to describe categorical and continuous variables, respectively. The Wilcoxon signed nonparametric test was used to determine any significant changes in CQ means pretrill and during trill. RESULTS: There was a significant decrease in the mean CQ during the Mediterranean tongue trill (Zalghouta) versus the sustained vowel [a] (P value of 0.002) by 15.98. When stratified by training status there was a significant decrease for the trained group (P value of 0.031) and a nonsignificant decrease for the untrained group (P value of 0.125). CONCLUSION: Zalghouta induces a decrease in the vocal fold contact time. The potential benefits of the Mediterranean tongue trill in vocal therapy need consideration. PMID- 22082866 TI - The effect of cochlear implantation on nasalance of speech in postlingually hearing-impaired adults. AB - OBJECTIVES/HYPOTHESIS: Hypernasality is considered a prevalent speech abnormality that could significantly contribute to the unintelligibility of the hearing impaired speakers. The aim of this study was to evaluate the effect of cochlear implantation and the duration of hearing loss on nasalance of speech of a postlingually impaired group of Saudi adult patients. STUDY DESIGN: Retrospective study. METHODS: This study included 25 postlingually hearing-impaired patients who underwent cochlear implantation and 25 age-matched control subjects. Patients were divided into three groups according to the duration of hearing loss. The nasometric data of the hearing-impaired group were compared with the control group. Also, the preoperative values were compared with the postoperative values 6, 12, and 24 months after surgery. RESULTS: Significant differences were demonstrated between the preimplantation nasalance scores of the three subgroups and between the patients and control groups. There were statistically significant differences demonstrated between the pre- and the postimplantation nasalance values for the three groups of patients. CONCLUSION: Cochlear implantation appears to have significant effects on improving the nasalance of the speech of postlingually hearing-impaired adult patients. However, the degree of improvement might vary according to the duration of hearing loss the patients had preimplantation. PMID- 22082867 TI - Validation and standardization of the Pediatric Voice Symptom Questionnaire: a double-form questionnaire for dysphonic children and their parents. AB - The aim of our study was to validate a Pediatric Voice Symptom Questionnaire (PVSQ) presenting with a parallel form for children and their parents. The items of the questionnaire were elaborated from the results of structured interviews with dysphonic children (DP) and normophonic children (NP) and their mothers and were tested for feasibility in a pilot study involving 42 normophonic children aged 5-13 years. The items were then administered in a test-retest mode to 333 children and their parents (154 boys and 179 girls with a mean age of 9 years, standard deviation: 1.8); 45 consulting DP, 34 nonconsulting dysphonics (NcDP), 163 NP, and 91 others. Classical statistical analyses and an item response modeling approach were used to analyze the results. High internal consistency and good test-retest stability were found. Significant differences between total score of the NP, DP, and NcDP groups were observed both in the children and the parents and also between parental and child score for the NP and NcDP groups (P<0.001-P=0.014). Correlations between child and parental scores were found only in the DP groups (r=0.478; P<0.001). Based on our results, the PVSQ is a valid and reliable instrument for the autoevaluation of dysphonia in the child population. PMID- 22082868 TI - Differences in vocal characteristics between Cantonese and English produced by proficient Cantonese-English bilingual speakers--a long-term average spectral analysis. AB - OBJECTIVES: The present study objectively examined the possible difference in vocal characteristics associated with English and Cantonese produced by proficient Cantonese-English bilingual speakers. SUBJECTS AND METHODS: Forty native speakers of Cantonese (20 males and 20 females) who were proficient in Cantonese and English participated in the study. An array of acoustical parameters, including fundamental frequency (F0) values and first spectral peak (FSP), mean spectral energy (MSE), and spectral tilt (ST) extracted from long term average speech spectra were obtained from connected speech samples produced in Cantonese and English by the bilingual speakers. Acoustical parameters were measured using Praat (P. Boersma & D. Weenink, Amsterdam, The Netherlands) and used to objectively describe the voice quality. RESULTS: Results indicated that female bilingual speakers had significantly higher F0 values in speaking English than Cantonese. Although exhibiting comparable FSP values, the bilingual speakers showed significantly higher MSE and lower ST values when speaking Cantonese compared with English. CONCLUSIONS: The present findings imply that, even with the same phonatory apparatus, language being spoken can have an effect on the speakers' voice quality. PMID- 22082869 TI - Activation of autophagy is required for muscle homeostasis during physical exercise. AB - Skeletal muscle fibers of collagen VI null (Col6a12/2) mice show signs of degeneration due to a block in autophagy, leading to the accumulation of damaged mitochondria and excessive apoptosis. Attempts to induce autophagic flux by subjecting these mutant mice to long-term or shorter bursts of physical activity are unsuccessful (see Grumati, et al., pp. 1415-23). In normal mice, the induction of autophagy in the skeletal muscles post-exercise is able to prevent the accumulation of damaged organelles and maintain cellular homeostasis. Thus, these studies provide an important connection between autophagy and exercise physiology. PMID- 22082870 TI - Impaired mitophagy at the heart of injury. AB - Recent publications link mitophagy mediated by PINK1 and Parkin with cardioprotection and attenuation of inflammation and cell death. The field is in need of methods to monitor mitochondrial turnover in vivo to support the development of new therapies targeting mitochondrial turnover. PMID- 22082871 TI - Expression pattern and functions of autophagy-related gene atg5 in zebrafish organogenesis. AB - The implications of autophagy-related genes in serious neural degenerative diseases have been well documented. However, the functions and regulation of the family genes in embryonic development remain to be rigorously studied. Here, we report on for the first time the important role of atg5 gene in zebrafish neurogenesis and organogenesis as evidenced by the spatiotemporal expression pattern and functional analysis. Using morpholino oligo knockdown and mRNA overexpression, we demonstrated that zebrafish atg5 is required for normal morphogenesis of brain regionalization and body plan as well as for expression regulation of neural gene markers: gli1, huC, nkx2.2, pink1, beta-synuclein, xb51 and zic1. We further demonstrated that ATG5 protein is involved in autophagy by LC3-II/LC3I ratio and rapamycin-induction experiments, and that ATG5 is capable of regulating expression of itself gene in the manner of a feedback inhibition loop. In addition, we found that expression of another autophagy-related gene, atg12, is maintained at a higher constant level like a housekeeping gene. This indicates that the formation of the ATG12-ATG5 conjugate may be dependent on ATG5 protein generation and its splicing, rather than on ATG12 protein in zebrafish. Importantly, in the present study, we provide a mechanistic insight into the regulation and functional roles of atg5 in development of zebrafish nervous system. PMID- 22082872 TI - Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an Atg12-5-16L2 complex. AB - A large protein complex consisting of Atg5, Atg12 and Atg16L1 has recently been shown to be essential for the elongation of isolation membranes (also called phagophores) during mammalian autophagy. However, the precise function and regulation of the Atg12-5-16L1 complex has largely remained unknown. In this study we identified a novel isoform of mammalian Atg16L, termed Atg16L2, that consists of the same domain structures as Atg16L1. Biochemical analysis revealed that Atg16L2 interacts with Atg5 and self-oligomerizes to form an ~800-kDa complex, the same as Atg16L1 does. A subcellular distribution analysis indicated that, despite forming the Atg12-5-16L2 complex, Atg16L2 is not recruited to phagophores and is mostly present in the cytosol. The results also showed that Atg16L2 is unable to compensate for the function of Atg16L1 in autophagosome formation, and knockdown of endogenous Atg16L2 did not affect autophagosome formation, indicating that Atg16L2 does not possess the ability to mediate canonical autophagy. Moreover, a chimeric analysis between Atg16L1 and Atg16L2 revealed that their difference in function in regard to autophagy is entirely attributable to the difference between their middle regions that contain a coiled coil domain. Based on the above findings, we propose that formation of the Atg12 5-16L complex is necessary but insufficient to mediate mammalian autophagy and that an additional function of the middle region (especially around amino acid residues 229-242) of Atg16L1 (e.g., interaction with an unidentified binding partner on phagophores) is required for autophagosome formation. PMID- 22082873 TI - Ins(1,4,5)P3 receptor-mediated Ca2+ signaling and autophagy induction are interrelated. AB - The role of intracellular Ca2+ signaling in starvation-induced autophagy remains unclear. Here, we examined Ca2+ dynamics during starvation-induced autophagy and the underlying molecular mechanisms. Tightly correlating with autophagy stimulation, we observed a remodeling of the Ca2+ signalosome. First, short periods of starvation (1 to 3 h) caused a prominent increase of the ER Ca2+-store content and enhanced agonist-induced Ca2+ release. The mechanism involved the upregulation of intralumenal ER Ca2+-binding proteins, calreticulin and Grp78/BiP, which increased the ER Ca2+-buffering capacity and reduced the ER Ca2+ leak. Second, starvation led to Ins(1,4,5)P3R sensitization. Immunoprecipitation experiments showed that during starvation Beclin 1, released from Bcl-2, first bound with increasing efficiency to Ins(1,4,5)P3Rs; after reaching a maximal binding after 3 h, binding, however, decreased again. The interaction site of Beclin 1 was determined to be present in the N-terminal Ins(1,4,5)P3-binding domain of the Ins(1,4,5)P3R. The starvation-induced Ins(1,4,5)P3R sensitization was abolished in cells treated with BECN1 siRNA, but not with ATG5 siRNA, pointing toward an essential role of Beclin 1 in this process. Moreover, recombinant Beclin 1 sensitized Ins(1,4,5)P3Rs in 45Ca2+-flux assays, indicating a direct regulation of Ins(1,4,5)P3R activity by Beclin 1. Finally, we found that Ins(1,4,5)P3R-mediated Ca2+ signaling was critical for starvation-induced autophagy stimulation, since the Ca2+ chelator BAPTA-AM as well as the Ins(1,4,5)P3R inhibitor xestospongin B abolished the increase in LC3 lipidation and GFP-LC3-puncta formation. Hence, our results indicate a tight and essential interrelation between intracellular Ca2+ signaling and autophagy stimulation as a proximal event in response to starvation. PMID- 22082874 TI - Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells. AB - Intracellular accumulation of altered proteins, including p62 and ubiquitinated proteins, is the basis of most neurodegenerative disorders. The relationship among the accumulation of altered proteins, autophagy, and spinal cord dysfunction by cervical spondylotic myelopathy has not been clarified. We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increased the expression of p62, ubiquitinated proteins, and LC3 II in neuronal cells. In addition, LC3 turnover assay and GFP-LC3 cleavage assay showed that hypoxic stress increased autophagy flux in neuronal cells. These findings suggest that hypoxic stress induces accumulation of p62 and autophagy in neuronal cells. The forced expression of p62 decreased the number of neuronal cells under hypoxic stress. These findings suggest that p62 accumulation under hypoxic stress promotes neuronal cell death. Treatment with 3-methyladenine, an autophagy inhibitor decreased the number of neuronal cells, whereas lithium chloride, an autophagy inducer increased the number of cells under hypoxic stress. These findings suggest that autophagy promotes neuronal cell survival under hypoxic stress. Our findings suggest that pharmacological inducers of autophagy may be useful for treating cervical spondylotic myelopathy patients. PMID- 22082876 TI - Mathematical arterialization of venous blood in emergency medicine patients. AB - OBJECTIVES: Arterial punctures represent a painful and unpleasant experience. Acid-base and oxygenation status can be assessed from peripheral venous blood, but agreement with arterial values is not always clinically acceptable. This study evaluates a method for mathematically transforming peripheral venous values into arterial values in emergency medicine patients. METHODS: Paired arterial and peripheral venous samples were analysed in groups A (47 patients) and B (101 patients), corresponding to the clinical need for arterial blood sampling (A) and without (B). Venous values were input into the mathematical arterialization method and the values of arterial pH, PCO2 and PO2 were calculated and compared with the measured values. RESULTS: The calculated and measured arterial pH and PCO2 values correlated well with the correlation coefficients (r ) of group A, pH 0.94, PCO2 0.97; group B, pH 0.87, PCO2 0.83; and Bland-Altman limits of agreement well within the limits of acceptable laboratory and clinical performance. The calculated values of arterial PO2 followed a set of predefined rules relating calculated and measured PO2 levels in all cases. The method represents an improvement on the use of venous blood alone where the correlation coefficients were as follows: group A, pH 0.85, PCO2 0.88; group B, pH 0.79, PCO2 0.59; and limits of agreement for PCO2 at the border of (group A) or beyond (group B) acceptable clinical limits. CONCLUSION: Application of the mathematical arterialization method may reduce the pain associated with assessment of acid base and oxygenation status, maximize the information obtained from peripheral venous blood and allow venous measurements to be presented as more commonly interpreted arterial values. PMID- 22082875 TI - Resveratrol-mediated autophagy requires WIPI-1-regulated LC3 lipidation in the absence of induced phagophore formation. AB - Canonical autophagy is positively regulated by the Beclin 1/phosphatidylinositol 3-kinase class III (PtdIns3KC3) complex that generates an essential phospholipid, phosphatidylinositol 3-phosphate (PtdIns(3)P), for the formation of autophagosomes. Previously, we identified the human WIPI protein family and found that WIPI-1 specifically binds PtdIns(3)P, accumulates at the phagophore and becomes a membrane protein of generated autophagosomes. Combining siRNA-mediated protein downregulation with automated high through-put analysis of PtdIns(3)P dependent autophagosomal membrane localization of WIPI-1, we found that WIPI-1 functions upstream of both Atg7 and Atg5, and stimulates an increase of LC3-II upon nutrient starvation. Resveratrol-mediated autophagy was shown to enter autophagic degradation in a noncanonical manner, independent of Beclin 1 but dependent on Atg7 and Atg5. By using electron microscopy, LC3 lipidation and GFP LC3 puncta-formation assays we confirmed these results and found that this effect is partially wortmannin-insensitive. In line with this, resveratrol did not promote phagophore localization of WIPI-1, WIPI-2 or the Atg16L complex above basal level. In fact, the presence of resveratrol in nutrient-free conditions inhibited phagophore localization of WIPI-1. Nevertheless, we found that resveratrol-mediated autophagy functionally depends on canonical-driven LC3-II production, as shown by siRNA-mediated downregulation of WIPI-1 or WIPI-2. From this it is tempting to speculate that resveratrol promotes noncanonical autophagic degradation downstream of the PtdIns(3)P-WIPI-Atg7-Atg5 pathway, by engaging a distinct subset of LC3-II that might be generated at membrane origins apart from canonical phagophore structures. PMID- 22082877 TI - Accuracy of urine dipstick in the detection of patients at risk for crush-induced rhabdomyolysis and acute kidney injury. AB - OBJECTIVES: To evaluate the utility of urine dipstick test (UDT) for detecting rhabdomyolysis and acute kidney injury (AKI) due to crush injury. METHODS: All the rescued victims of the Bam earthquake who had a documented urine analysis and serum creatine phosphokinase and creatinine levels during their hospitalization period were eligible to enter the study. The sensitivity and the specificity, along with the positive and negative likelihood ratios, of UDT in detecting at risk patients for rhabdomyolysis and crush-related AKI were calculated. RESULTS: Urine red blood cell count of 5 or less in blood-positive UDT, as a surrogate marker for myoglobinuria, was reported in 210 (31.7%) of the total 1821 urine analyses. Blood-positive UDTs (without considering the urine red blood cell count) had a 92.5% (95% confidence interval: 79.6-98.4) sensitivity in creatine phosphokinase, with a cut-off of 15,000 (IU/l). Comparing the results of the serum creatinine level and the urine blood, analysis showed that UDT had a sensitivity and a specificity of as high as 83.3 and 56.6% in detecting high-risk patients for AKI, respectively. CONCLUSION: UDT can be considered as an early screening tool for the detection and triage of patients at risk of developing AKI because of traumatic rhabdomyolysis after mass disasters. PMID- 22082878 TI - Absolute blood eosinophil count and 1-year mortality risk following hospitalization with acute heart failure. AB - OBJECTIVE: In acute heart failure (AHF), hemoglobin, red cell distribution width, mean platelet volume, leukocytes, and relative lymphocyte count have been associated with mortality. It is not known whether absolute blood neutrophil, eosinophil, and monocyte counts are mortality predictors. METHODS: One hundred and seventy-six patients hospitalized due to AHF were enrolled. Treatment modalities and comorbidities influencing leukocyte counts were excluded. Hemogram, pro-brain natriuretic peptide, D-dimer, biochemistry, thyroid hormones, sensitive C-reactive protein, and echocardiography were obtained. Cardiovascular deaths during the first year after hospitalization were determined. RESULTS: Leukocyte and absolute neutrophil count were significantly higher and absolute lymphocyte count and absolute eosinophil count (AEC) were significantly lower in deceased patients than patients who survived. Groups were similar in terms of monocyte counts. BMI albumin, estimated glomerular filtration rate, free T3, ejection fraction were significantly lower, and ferritin, uric acid, D-dimer, pro brain natriuretic peptide were significantly higher in deceased patients. Mitral regurgitation, hypotension, hyponatremia, and acute renal failure were also significantly more frequent among the deceased group. Binary logistic regression analysis employing significant variables showed that lower BMI, lower ejection fraction, hyponatremia, lower free T3, and lower AEC were independent predictors of death and as a whole were responsible from 81.8% of cardiovascular deaths. Death rate among patients with an AEC of 0.02 n/l*10 or less was 4.4-fold higher than patients with an AEC of more than 0.02 n/l*10. CONCLUSION: AEC of AHF patients measured at admission was found to be a stronger predictor of mortality than all other hemogram parameters and this is consistent with the increased sympatho-adrenal activity theory. PMID- 22082879 TI - The Clinical Decision Unit has a role to play in the management of acute undifferentiated abdominal pain. AB - INTRODUCTION AND AIMS: Patients with undifferentiated acute abdominal pain (AAP) frequently present to the Emergency Department (ED). The most common diagnosis is the nonspecific abdominal pain although missed occult surgical pathology in the haemodynamically stable patient with equivocal symptoms and signs is a potential source of morbidity. The objectives of this study were two-fold. Firstly, to ascertain the accuracy of ED clinicians in the diagnosis of AAP, and to delineate if there was a population of patients who would normally require admission to hospital that would be suitable to be managed on a Clinical Decision Unit (CDU) protocol. Secondly, to prospectively evaluate such a strategy by way of a pilot study. METHODS: An initial retrospective cohort study of consecutive patients presenting to the ED with undifferentiated AAP were analysed. Data were extracted on admission, length of stay and the correlation between initial ED clinical diagnosis and final discharge diagnosis. Following this, a protocol was developed within our institution for the management of patients with stable AAP on a CDU pathway. This was then formally evaluated over a period of 25 months as part of a quality improvement exercise. RESULTS: A total of 501 patients were analysed of whom 48% were admitted from the ED. The initial ED diagnosis was correct in 57% of patients, and 28% of admitted patients were discharged within 48 h with no specific intervention. During the period of the pilot study, 189 patients were entered on to the AAP CDU pathway, of which 85% were safely discharged directly from the CDU and 67% within 24 h. Of the 28 patients admitted only four required an operation. Use of the protocol in this population resulted in the initial ED assessment being correct in 69% of cases. CONCLUSION: The management of stable AAP within the ED environment on a well-defined CDU pathway is feasible and can facilitate safe, efficient and effective care with early discharge and an increase in the accuracy of the final diagnosis. PMID- 22082880 TI - Evaluating human, social and cultural capital in nurse education. AB - Using the concepts of human, social and cultural capital this paper will review the literature on these theories and evaluate their application to nurse education in the United Kingdom (UK). Each concept will be explored before considering the impact and application within nurse education. Issues of sponsorship via mentoring and increased skills and contribution to the knowledge economy alongside the delivery of quality care by nursing students will be discussed with reference to theory and current policy drivers. As nursing education moves to a graduate profession in the UK this paper evaluates the drivers of human, social and cultural capital that affect this development. PMID- 22082881 TI - Impact of a web based interactive simulation game (PULSE) on nursing students' experience and performance in life support training--a pilot study. AB - The delivery of effective life support measures is highly associated with the quality, design and implementation of the education that underpins it. Effectively responding to a critical event is a requirement for all nurses illustrating the need for effective educational approaches from pre-registration training through to enhancing and maintaining life support skills after qualification. This paper reports the findings of utilising a web-based multimedia simulation game PULSE (Platform for Undergraduate Life Support Education). The platform was developed to enhance the student experience of life support education, to motivate on-going learning and engagement and to improve psychomotor skills associated with the provision of Intermediate Life Support (ILS) training. Pre training participants played PULSE and during life support training data was collected from an intervention and a control group of final year undergraduate nursing students (N=34). Quantitative analysis of performance took place and qualitative data was generated from a questionnaire assessing the learning experience. A statistically significant difference was found between the competence the groups displayed in the three skills sets of checking equipment, airway assessment and the safe/effective use of defibrillator at ILS level, and PULSE was positively evaluated as an educational tool when used alongside traditional life support training. PMID- 22082882 TI - Relationship between kyphosis and Barrett's esophagus in Japanese patients. AB - BACKGROUND: Kyphosis is a risk factor for the presence of hiatal hernia, which is a strong predictor of Barrett's esophagus. However, the association between kyphosis and Barrett's esophagus has not yet been clarified. To investigate this relationship, the Cobb angle, a marker of kyphosis, was measured in patients with and without Barrett's esophagus. METHODS: From January 2006 to December 2010, 26 patients with long-segment Barrett's esophagus (LSBE) were retrospectively enrolled. As the comparative groups, 100 consecutive patients with short-segment Barrett's esophagus (SSBE) and 100 consecutive control patients without Barrett's esophagus were also enrolled in this study. Cobb angles were measured on lateral chest radiographs, and kyphosis was defined as a Cobb angle of greater than 50 degrees . Kyphosis, along with other patient characteristics, were evaluated as possible predictors for SSBE and LSBE. RESULTS: The mean Cobb angles in the non BE, SSBE, and LSBE groups were 31.6 degrees (95% CIs, 29.3 degrees -33.9 degrees ), 34.8 degrees (32.1 degrees -37.4 degrees ) and 49.4 degrees (44.9 degrees 53.9 degrees ), respectively. Statistically significant differences were found between the LSBE and the other 2 groups (p<0.001). The mean Cobb angles were 33.3 degrees +/-12.4 degrees and 37.0 degrees +/-14.1 degrees , respectively in patients without and with hiatal hernia (p=0.039). Predictors for Barrett's esophagus of any length were erosive esophagitis and hiatal hernia. Kyphosis had the highest odds ratio for the presence of LSBE (OR, 1.50; 95% CI, 1.05-1.94; p=0.033). Other predictors were hiatal hernia and the absence of Helicobacter pylori infection. CONCLUSION: Kyphosis is a risk factor for the presence of LSBE in Japanese patients. PMID- 22082883 TI - Partial splenic embolization facilitates the adherence to peginterferon in chronic hepatitis C with thrombocytopenia. AB - OBJECTIVE: Platelet counts before starting the treatment affect the discontinuation and dose reduction of peginterferon in chronic hepatitis C. Thrombocytopenia leads to failure to achieve sustained virological response. This study was undertaken to evaluate the efficacy of partial splenic embolization (PSE) prior to starting peginterferon therapy combined with ribavirin in chronic hepatitis C patients showing thrombocytopenia. PATIENTS AND METHODS: We compared the clinical features of 11 patients receiving PSE (PSE group) prior to starting the combined therapy with those of 13 patients not receiving PSE (non-PSE group). All of the patients showed platelet counts <=12*10(4)/mm(3) and serum hepatitis C virus-RNA levels >=100 KIU/mL at baseline. The end-point of PSE was a volume of splenic infarction over 75%. Peginterferon alpha-2b at a dose of 1.2 ug/kg was administered by subcutaneous injection once a week. The dose of ribavirin was weight adjusted. RESULTS: PSE was successfully performed without serious adverse events. The period from PSE to starting the combined therapy was 14 (6-27) days. After PSE, platelet counts were significantly increased. In PSE group, platelet counts during the combined therapy were maintained above those at baseline. In non-PSE group, platelet counts at the 2nd week after the start of the combined therapy significantly decreased to less than those at baseline. Overall, 80% adherence to expected peginterferon dose was not achieved in 5 patients (45%) of PSE group and in 11 (85%) of non-PSE group (p=0.043). CONCLUSION: Increased platelet counts after PSE facilitates the adherence to peginterferon therapy in chronic hepatitis C patients with thrombocytopenia. PMID- 22082884 TI - Rice cake ileus--a rare and ethnic but important disease status in east-southern Asia. AB - INTRODUCTION: Rice cake is a traditional but very popular food in Asia including Japan and has never been known as a cause of ileus. Rice cake is now becoming widespread in the United States and European countries along with other Japanese foods. We may encounter rice cake ileus all over the world. This study was aimed at characterizing the rice cake ileus. METHODS: We consecutively encountered 14 patients with rice cake ileus from April 2003 to October 2010 in our hospital. All of the characteristics of the cases were reviewed and analyzed. RESULTS: All patients had ingested rice cake by swallowing without chewing. It has most frequently occurred in January (57.1%). The main symptoms were abdominal colicky pain (100%) and nausea (85.7%) and physical findings included abdominal tenderness (100%) and muscular defense (28.6%). All patients improved by conservative therapy including fluid supply (100%), naso-gastric tube (28.6%) and long tube (28.6%) insertion. No patient needed emergency open surgery. CONCLUSION: Rice cake ileus which is caused by swallowing the rice cake without chewing, frequently occurs in January, has previous history of abdominal surgery and shows high density intestinal contents on CT and only needs conservative therapy. Globalism in food culture may provide a new disease entity. Therefore, we should be aware of this type of ileus and be prepared to manage it appropriately. PMID- 22082885 TI - Blood pressure and sympathetic nerve tone relation during hemodialysis may reflect cardiovascular dysfunction. AB - BACKGROUND: The blood pressure response to the rapid removal of fluid during hemodialysis is complex and the pathophysiological mechanisms underlying intradialytic hypotension are not clear and sometimes these mechanisms render dialysis difficult to continue. PURPOSE: We analyzed the changes in blood pressure and sympathetic nerve tone and attempted to clarify whether the dynamic pattern of this relationship reflects cardiovascular dysfunction. METHODS: The dynamic pattern of sympathetic nerve activity throughout dialysis was analyzed by frequency analysis of RR intervals recorded by 24 hours Holter electrocardiography in 64 patients and 3 minutes ECG every 15 minutes during dialysis in 121 stable end-stage renal failure patients who underwent maintenance hemodialysis. Blood pressure and fluid volume removed was measured every 15-30 minutes during dialysis and the average value of the ratio of low to high frequency components (LF/HF) was calculated as an index of sympathetic nerve tone. The relationship between removed fluid volume, systolic blood pressure (Bp) and LF/HF was analyzed. RESULTS: The patients were classified into 3 groups based on the correlation between the LF/HF and Bp as follows: positive (52 cases), inverse (54 cases), and not significant (NS; 61 cases). Eighteen patients who showed multiple arrhythmias, atrial fibrillation and other artifacts or noises were eliminated as they were inadequate for frequency analysis of RR intervals. The positive group was characterized by a hypotension-resistant response with a low LF/HF, whereas the inverse group was characterized by a hypotension-prone response with high LF/HF. These results suggest that cardiovascular dysfunction is responsible for the inverse correlation. CONCLUSION: Analysis of the relationship between sympathetic nerve tone and Bp is effective in predicting the existing of cardiovascular dysfunction. PMID- 22082886 TI - Prevalence of preexisting metabolic syndrome as defined by Japanese original criteria among patients with non-fatal myocardial infarction. AB - OBJECTIVE: We aimed to clarify the prevalence of preexisting Metabolic Syndrome (MetS) defined by the Japanese original criteria among patients with non-fatal myocardial infarction (MI). METHODS: This is a retrospective cohort study using the computer database obtained by the preliminary health checkup from April 2003 to December 2008. We extracted the subjects with newly developed non-fatal MI from the study population. The newly non-fatal MI was diagnosed by the history of coronary heart disease (CHD) and new appearance of abnormal Q wave on electrocardiograms. MetS was diagnosed by using the Japanese original criteria. If waist circumference was not available, BMI was used alternatively. We evaluated the prevalence of preexisting MetS and other risk factors of CHD among the subjects. We compared the prevalence of preexisting risk factors between MetS group and non-MetS group. RESULTS: From a study population of 298,455 subjects, 446 subjects with a history of CHD were found. Among the 446, 92 subjects (85 men and 7 women) with abnormal Q wave on electrocardiogram were found. The prevalence of preexisting MetS with non-fatal MI was 19.6% (95% CI; 15.5-23.7%). The prevalence of other preexisting risk factors were 60.0% with smoking history, 55.6% with over-work, 53.3% with stressful life and 36.1% with impaired glucose tolerance. These prevalence rates were not significantly different between MetS group and non-MetS group. Only the prevalence (22.3%) of elevated LDL-cholesterol in the non-MetS group was significantly higher than in the MetS group (14.4%). CONCLUSION: Preexisting MetS may be able to predict only 20% of future MI. To prevent future myocardial infarction, precaution guidance may be required for people with not only preexisting MetS but also other preexisting risk factors of CHD. PMID- 22082887 TI - Association of hemoglobin with ambulatory arterial stiffness index in untreated essential hypertensive patients without anemia. AB - OBJECTIVE: Increased hemoglobin (Hb) levels are known to be associated with increased cardiovascular events and mortality in hypertensive patients, but the underlying mechanism remains unclear. However, an increased Ambulatory Arterial Stiffness Index (AASI), the surrogate maker of arterial stiffness, has been proven to be an independent predictor of cardiovascular disease. This pilot study evaluated the association between Hb and AASI in untreated essential hypertensive patients without anemia. METHODS: A total of 566 untreated essential hypertensive patients without anemia were divided into Normal-Hb and High-Hb groups according to their Hb levels. The AASI and its symmetric calculation (Sym_AASI) were derived from 24h-Ambulatory Blood Pressure Monitoring (24h-ABPM). A multivariable linear regression analysis was performed to determine the relationship between Hb and AASI, Sym_AASI. RESULTS: High-Hb group (n=127) showed higher AASI and Sym_AASI (0.51+/-0.11 vs 0.43+/-0.12, p<0.001; 0.33+/-0.10 vs 0.27+/-0.08, p<0.001) compared to Normal-Hb group (n=439). Univariate correlation analysis showed that Hb levels were positively related to AASI and Sym_AASI values (r=0.459, p<0.001; r=0.353, p<0.001). After adjustment for age, sex, BMI, current smoker, eGFR, uric acid, total cholesterol, high-density lipoprotein, 24h-SBP, 24h-PP and dipper status, Hb persisted as a independent determinant of AASI and Sym_AASI (beta=0.402, p<0.001 and beta=0.298, p<0.001, respectively). CONCLUSION: High hemoglobin seems be to associated with increased AASI in untreated essential hypertensive patients without anemia. PMID- 22082888 TI - Significant correlation between visceral adiposity and high-sensitivity C reactive protein (hs-CRP) in Japanese subjects. AB - OBJECTIVE: High-sensitivity C-reactive protein (hs-CRP) is a marker for low-grade inflammation, as well as atherosclerosis, obesity, hyperglycemia and hypertension. Because the factor showing the strongest association with inflammation is currently unknown, we investigated the associations between hs CRP and clinical and biochemical characteristics in Japanese subjects with mild obesity or impaired glucose tolerance. METHODS: Subjects aged <65 years old, attending the Seirei Medical Examination Center, underwent complete physical and laboratory examinations. A total of 112 subjects (mean age 59.9+/-5.9 years old, males/females: n=50/62) with a waist circumference of >85 cm in males and >90 cm in females, homeostasis model assessment-insulin resistance (HOMA-IR) >=1.7, or impaired glucose tolerance were eligible for this study. All subjects had normal albuminuria. RESULTS: Log-transformed hs-CRP concentrations were significantly correlated with BMI (r=0.278, p<0.01), HOMA-IR (r=0.296, p<0.005), 2-h post challenge IRI during an oral glucose tolerance test (r=0.218, p<0.05), maximum intima-media thickness (r=0.240, p<0.05), visceral fat area evaluated by computed tomography (r=0.423, p<0.0001) and subcutaneous fat area (r=0.231, p<0.05). Multiple linear regression analysis showed that visceral fat was the most significantly correlated factor with hs-CRP. CONCLUSION: Visceral fat mass was a significant and independent predictor for serum hs-CRP levels in Japanese subjects with mild obesity and/or impaired glucose tolerance. PMID- 22082889 TI - PSP as distinguished from CBD, MSA-P and PD by clinical and imaging differences at an early stage. AB - OBJECTIVE: Because it is often difficult to precisely diagnose and distinguish progressive supranuclear palsy (PSP) from corticobasal degeneration (CBD), multiple system atrophy-parkinsonism (MSA-P) and Parkinson's disease (PD) at the onset of the disease, we compared the patients and clarified the features of these diseases. METHODS: We compared 77 PSP, 26 CBD, 26 MSA-P and 166 PD patients from clinical and imaging points of view including cerebral blood flow (CBF) in the frontal eye field. RESULTS: The clinical characteristics of PSP were supranuclear gaze disturbance, optokinetic nystagmus (OKN) impairment and falls at the first visit. On head MRI, midbrain tegmentum atrophy was much more frequently detected in PSP than in all of the other groups. Heart-to-mediastinum average count ratio (H/M) in iodine-123 meta-iodobenzyl guanidine ((123)I-MIBG) myocardial scintigraphy was not decreased in PSP, CBD, MSA-P and PD-Yahr 1 (-1), but patients of PD-2, 3, 4 and 5 showed a significant decrease compared with the PSP group. The CBF in the left frontal eye field of PD-3 group and that in right frontal eye field of PD-3 and PD-4 groups were lower than that of PSP group, although other groups showed a tendency without a significant decrease compared with PSP group. CONCLUSION: PSP is distinguishable from CBD, MSA-P and PD even at the early stage with extra-ocular movement (EOM) disturbance, falls, atrophy of the midbrain tegmentum, and H/M in (123)I-MIBG myocardial scintigraphy, and the reduction of CBF in area 8 could serve as a supplemental diagnostic method for distinguishing PSP from PD-3 or PD-4. PMID- 22082890 TI - Diagnosis of invasive fungal disease using serum (1->3)-beta-D-glucan: a bivariate meta-analysis. AB - BACKGROUND: The (1->3)-beta-D-Glucan (BG) assay has been approved for diagnosing invasive fungal disease (IFD). However, the test performance has been variable. We conducted a meta-analysis to determine the overall accuracy of BG assay for diagnosing IFD. METHODS: The sensitivity, specificity, and positive and negative likelihood ratios (PLR and NLR, respectively) of BG for diagnosing IFD were pooled using a bivariate meta-analysis. We also performed subgroup analyses. RESULTS: Twelve reports, including 15 studies, were included for the analysis (proven and probable IFD vs possible or no IFD). The sensitivity, specificity, PLR and NLR were 0.76 (95% CI, 0.67-0.83), 0.85 (95% CI, 0.73-0.92), 5.05 (95% CI, 2.71-9.43), and 0.28 (95% CI, 0.20-0.39), respectively. Subgroup analyses showed that the BG assay had higher specificities for patients with hematological disorders and a positive BG result with two consecutive samples. The combination of galactomannan and BG increased the specificity value to 0.98 (95% CI, 0.95 0.99) for diagnosing invasive aspergillosis. CONCLUSION: Serum BG determination is clinically useful for diagnosing IFD in at-risk patients, especially for hematology patients. The combination of galactomannan and BG was sufficient for diagnosing invasive aspergillosis. Since the BG assay is not absolutely sensitive and specific for IFD, the BG results should be interpreted in parallel with clinical findings. PMID- 22082891 TI - Management and treatment of osteoporosis in patients receiving long-term glucocorticoid treatment: current status of adherence to clinical guidelines and related factors. AB - OBJECTIVE: The aim of this study was to evaluate the adherence of guidelines for the management and treatment of glucocorticoid-induced osteoporosis, and to investigate whether it is associated with factors such as age, gender, glucocorticoid dose, physician specialty, and size of facility. METHODS: This was a cross-sectional study utilizing administrative data from a database of health insurance claims (2004-2007); 2,368 patients who received glucocorticoid treatment for >=90 days were extracted. The guideline adherence was determined by evaluations based on glucocorticoid prescription dose, prescription of anti osteoporosis drugs, and whether or not bone mineral density was measured. RESULTS: Overall proportion of guideline adherence was 23.3%. In cases in which the equivalent dose of prednisolone was <5 mg/d and >=5 mg/d, the adherence was 8.3% and 30.5% respectively. Factors correlating with low adherence included young age, male gender, and lower glucocorticoid doses. Surgery and otolaryngology specialties had lower adherence than internal medicine. Smaller clinical facilities had lower adherence than larger facilities. CONCLUSION: The adherence of guidelines for the management and treatment of glucocorticoid induced osteoporosis is still low, and improvements in treatment quality can be expected through education of patient groups and medical care providers with large deviations from the guidelines. PMID- 22082892 TI - A case of thyroid storm with multiple organ failure effectively treated with plasma exchange. AB - We describe a 48-year-old man with thyroid storm presenting with heart failure. He presented severely impaired left ventricular wall motion and a marked increase in the liver enzymes. He developed disseminated intravascular coagulation on day 2. Due to elevated serum thyroid hormone level, anti-thyroid hormone receptor antibody positivity, and his clinical symptoms, he was diagnosed as thyroid storm due to untreated Graves' disease. His condition did not improve even after 6 days of conventional therapy including steroids. After therapeutic plasma exchange was carried out, his thyroid hormone level decreased markedly. Consequently, his condition recovered gradually, and he was discharged at day 43. PMID- 22082893 TI - Pulmonary tumor thrombotic microangiopathy associated with esophageal squamous cell carcinoma. AB - Pulmonary tumor thrombotic microangiopathy (PTTM) is an uncommon cancer-related complication that has been most frequently reported to be associated with adenocarcinoma. We present a case of PTTM which developed in a 60-year-old man with esophageal carcinoma. One year after definitive treatment of the tumor, he developed pulmonary hypertension. Transbronchial lung biopsy (TBLB) specimens showed fibrocellular intimal proliferation and luminal stenosis of the small pulmonary vessels, which contained squamous cell carcinoma cells. Thus, PTTM associated with esophageal carcinoma was diagnosed. This is the first reported case of PTTM associated with esophageal squamous cell carcinoma. TBLB seemed to be useful for obtaining a definitive diagnosis. PMID- 22082894 TI - A pitfall of fractional flow reserve associated with the presence of collateral circulation. AB - An 82-year-old man had a severe stenosis in the proximal left anterior descending artery (LAD) and an intermediate stenosis in the distal right coronary artery (RCA). The territory of mid to distal LAD was perfused via an angiographically well-developed collateral circulation from the distal RCA. Fractional flow reserve (FFR) in the distal RCA was 0.84. After successful coronary intervention for the proximal LAD, repeat FFR in the distal RCA was 0.96. In this case, the severity of the stenosis in the donor artery was overestimated by using FFR due to the presence of well-developed collateral circulation. PMID- 22082895 TI - An appropriate defibrillation threshold obtained by the combined connection between two shock leads and ICD generator. AB - A 60-year-old man with arrhythmogenic right ventricular cardiomyopathy was readmitted for the battery exchange of his implantable cardioverter-defibrillator (ICD). Since (i) he had been treated with a dual-coil shock lead (Sprint Fidelis, Medtronic) and (ii) pre-operative venography showed mild collateral flow to the left subclavian vein, a single-coil lead was additionally implanted. However, the single-coil defibrillation system was unable to terminate the induced ventricular fibrillation (VF), thus dual defibrillation shock pathways were created using the connection to the superior vena cava coil of the Fidelis lead. The combined connections of the two shock leads provided an appropriate margin of the defibrillation threshold. PMID- 22082896 TI - Notable pink excreta and severe myocardial suppression in superwarfarin (difethialone) intoxication. AB - Patients rarely consult physicians before developing coagulopathy or bleeding in most reported cases of superwarfarin intoxication. A 57-year-old woman ingested red-dyed pellets of anticoagulant rodenticide containing difethialone and warfarin as well as tablets of nitrazepam. Although she presented to the hospital in a comatose state, notable pink-colored excreta hinted at the consumption of anticoagulant rodenticide, which led to the early diagnosis of superwarfarin intoxication. Supplementation of large doses of intravenous and oral vitamin K successfully prevented coagulopathy and bleeding. On the other hand, temporary and reversible myocardial suppression was extremely severe, and required the introduction of percutaneous cardiopulmonary support. PMID- 22082897 TI - Severe obliterative bronchitis associated with Stevens-Johnson syndrome. AB - We report a case of Stevens-Johnson syndrome (SJS) in which the patient had been diagnosed with severe obliterative bronchitis. A 29-year-old woman was admitted with a high fever and a widespread vesicular rash. She was diagnosed with SJS and betamethasone administration was started. After one month, her vesicular skin rash improved; however, she developed respiratory failure and was assisted with mechanical ventilation. Computed tomography of the chest demonstrated a hyperlucent lung with narrowing of the peripheral vessels. Bronchoscopy revealed an occlusion of the bronchus when the patient exhaled. The flow-volume curve revealed a severe obstructive pattern. The patient was diagnosed with obliterative bronchitis following SJS. She was treated with a bronchodilator and steroids, but could not breathe adequately without the ventilator. During the following year, her PaCO(2) increased to 100 torr and her heart function also continued to worsen. Despite intensive treatment, she died one year and seven months after the onset of SJS. In SJS and toxic epidermal necrolysis (TEN) patients, chronic pulmonary complications are rare, but there is no effective therapy for obliterative bronchitis following SJS/TEN. Therefore, early awareness of this condition is needed and lung transplantation must be considered at an early stage of this disease. PMID- 22082898 TI - Neuromyelitis optica in Japanese sisters. AB - We report cases of Japanese sisters with neuromyelitis optica (NMO). The elder sister was 25, when she was diagnosed with right optic neuritis. After 3 months, she developed left optic neuritis and myelitis. At age 27, she had the second relapse, but she has been free from episodes thereafter. The younger sister was 26, when she was diagnosed with optic neuritis. Thus far, she has 9 relapses, comprising both myelitis and optic neuritis. Both sisters had normal brain MRI scans, longitudinally extensive transverse myelitis over 3 vertebral segments, and positive results for anti-aquaporin-4 antibody (AQAP4Ab). They fulfilled the Wingerchuk criteria for definite NMO. Both sisters shared some immunogenetic factors, but they were not exposed to the same environmental factors after their early twenties. The final disability status was almost the same in both cases, and both showed a very benign course. These data suggest that genetic factors affect the age at onset and environmental factors may affect the frequency of relapse. PMID- 22082899 TI - p.Arg332Cys mutation of NOTCH3 gene in two unrelated Japanese families with CADASIL. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a cerebrovasuclar disease caused by NOTCH3 mutations, usually localized to exons 3 and 4. This report describes the clinical and neuroradiological findings of 2 subjects of two unrelated Japanese families who shared a common p.Arg332Cys mutation. The subject from family A presented syncope attacks as the sole clinical presentation at the beginning of his disease course. The subject from family B showed recurrent ischemic attacks, followed by a large intracranial hemorrhage. This is the first report to describe the detailed phenotypes of patients with a rare p.Arg332Cys mutation in Japan. PMID- 22082900 TI - A Japanese case with Nasu-Hakola disease of DAP12 gene mutation exhibiting precuneus hypoperfusion. AB - A 38-year-old Japanese man with Nasu-Hakola disease (NHD) had repeated pathological fractures and frontal lobe symptoms which developed when he was 18 and 26 years old, respectively. Neuropsychological testing showed memory impairment, and in particular, visuo-spatial memory at the age of 35. Furthermore, single-photon emission computed tomography revealed precuneus hypoperfusion. The patient later suffered prolonged convulsive seizures, which left him in a persistent vegetative state. Genetic testing confirmed a heterozygous mutation in the DAP12 gene (a single-base deletion of 141 G in exon 3) specific to NHD. Precuneus dysfunction might contribute to characteristic memory impairment of NHD. PMID- 22082901 TI - Sclerosing mesenteritis presenting as protein-losing enteropathy: a fatal case. AB - Sclerosing mesenteritis is a rare, benign disorder characterized by non-specific and chronic inflammation of the mesenteric adipose tissue. The disease usually presents with gastrointestinal symptoms and abdominal masses. The long-term prognosis is favorable, but it often becomes severe. In the present report we describe a 77-year-old man who presented with diarrhea, massive ascites and an abdominal mass. The rapid deterioration of the general condition of the patient limited invasive examinations and left the primary disease unclear. Despite symptomatic therapy, malnutrition and hypovolemia were prolonged, and he died. The definitive diagnosis of sclerosing mesenteritis and the cause of the fatal outcome were disclosed at autopsy. This case indicates that sclerosing mesenteritis is a potentially-fatal disease and the need for aggressive treatment should be discussed. PMID- 22082902 TI - Fulminant amebic colitis in an HIV-infected homosexual man. AB - We present a case of fulminant amebic colitis in a human immunodeficiency virus (HIV)-infected homosexual man. The patient developed colonic perforation over a short time despite empirical therapy with metronidazole, and underwent right hemicolectomy. Amebic colitis was pathologically diagnosed by identifying invasive trophozoites of Entamoeba in a surgical specimen. Amebic colitis is one of the important differential diagnoses of acute abdomen in HIV-infected patients and/or homosexual men, especially in East Asia. Although fulminant amebic colitis is a rare manifestation of amebiasis, early diagnosis and treatment are thought to be important to improve the outcome of this highly fatal complication. PMID- 22082903 TI - Visceral leishmaniasis mimicking as second line anti retroviral therapy failure. AB - Visceral leishmaniasis (VL) has increased as a complicating infection in subjects with human immunodeficiency virus (HIV) in developing countries. Both infections tend to lower the cell-mediated immunity resulting in poor drug response. In HIV positive subjects the clinical course as well as organ involvement of VL simulates tuberculosis, another very common tropical infection. We present a case of VL/HIV co-infection where the individual failed to respond to first and second line antiretroviral therapy with persistently low CD4 counts. This patient was also subjected empirically to antitubercular therapy with no clinical improvement; he was finally diagnosed as a case of VL in HIV upon revelation of amastigotes in bone marrow despite the initial negative serology on two occasions. He showed dramatic improvement in CD4 counts and clinical status on Amphotericin B therapy. In endemic areas and in HIV positive subjects a systemic and careful parasitology follow-up is necessary to ensure that no clinical form of leishmaniasis is overlooked. PMID- 22082904 TI - Emphysematous pyelonephritis concurrent with psoas muscle abscess. PMID- 22082905 TI - Polymorphic ventricular tachycardia complicated with Cushing syndrome. PMID- 22082906 TI - Isolated impairment of confrontation naming task due to left premotor subcortical infarct. PMID- 22082907 TI - Thoracic sandwich sign. PMID- 22082908 TI - Thinker's sign. PMID- 22082909 TI - Autoantibody profile and other immunological parameters in recurrent spontaneous abortion patients. AB - BACKGROUND: An autoimmune cause and related immunological alterations resulting in recurrent spontaneous abortion (RSA) have been suggested in patients with unknown etiology. MATERIALS AND METHODS: This study evaluated the autoantibody profile and other immunological parameters among RSA patients and normal pregnant women from Mumbai western India. Fifty RSA patients with unknown cause and greater than three consecutive abortions along with 50 normal pregnant women were studied for various auto antibodies such as ANA, anti-dsDNA, ANCA, AECA, 2 micro globulin, anti-HLA antibodies and ACLA using immunofluorescence microlymphocytotoxicity and ELISA. Immunological parameters such as HLA class I monoclonal antibody expression, CD3 (T cell), CD19 (B cell), and CD56 (NK cell) were estimated by flow cytometry. RESULTS: The results revealed 34% positivity of all auto antibodies tested among patients. ANA(12%), ANCA (20%), AECA (24%), ACLA (8%), anti-dsDNA(0%), beta2 microglobulin (14%), and anti-HLA antibodies(10%) among RSA patients were identified. An increased expression of HLA class I specific monoclonal antibody (10%) with HLA A3 (16%) specificity were found to correlate with shared HLA alleles among the RSA couples. Among normal pregnant (control) group ANA (2%), ANCA (2%), AECA (3%), ACLA (4%) and increased expression of CD56 with reduced HLA class I monoclonal were observed. CONCLUSION: Our findings suggest a possible role of various autoantibodies along with the related immunological parameters underlying RSA. PMID- 22082910 TI - Deciphering the transcriptional regulatory logic of amino acid metabolism. AB - Although metabolic networks have been reconstructed on a genome scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here we reconstruct such an integrated network for amino acid metabolism in Escherichia coli. Analysis of ChIP-chip and gene expression data for the transcription factors ArgR, Lrp and TrpR showed that 19 out of 20 amino acid biosynthetic pathways are either directly or indirectly controlled by these regulators. Classifying the regulated genes into three functional categories of transport, biosynthesis and metabolism leads to the elucidation of regulatory motifs that constitute the integrated network's basic building blocks. The regulatory logic of these motifs was determined on the basis of relationships between transcription factor binding and changes in the amount of transcript in response to exogenous amino acids. Remarkably, the resulting logic shows how amino acids are differentiated as signaling and nutrient molecules, revealing the overarching regulatory principles of the amino acid stimulon. PMID- 22082912 TI - Re: comparison of laparoendoscopic single-site radical nephrectomy with conventional laparoscopic radical nephrectomy for localized renal-cell carcinoma. PMID- 22082913 TI - Re: laparoendoscopic single-site surgery versus standard laparoscopic simple nephrectomy: a prospective randomized study. PMID- 22082911 TI - A neutral diphosphate mimic crosslinks the active site of human O-GlcNAc transferase. AB - Glycosyltransferases (Gtfs) catalyze the formation of a diverse array of glycoconjugates. Small-molecule inhibitors to manipulate Gtf activity in cells have long been sought as tools for understanding Gtf function. Success has been limited because of challenges in designing inhibitors that mimic the negatively charged diphosphate substrates. Here we report the mechanism of action of a small molecule that inhibits O-linked N-acetylglucosamine transferase (OGT), an essential human enzyme that modulates cell signaling pathways by catalyzing a unique intracellular post-translational modification, beta-O-GlcNAcylation. The molecule contains a five-heteroatom dicarbamate core that functions as a neutral diphosphate mimic. One dicarbamate carbonyl reacts with an essential active site lysine that anchors the diphosphate of the nucleotide-sugar substrate. A nearby cysteine then reacts with the lysine adduct to form a carbonyl crosslink in the OGT active site. Though this unprecedented double-displacement mechanism reflects the unique architecture of the OGT active site, related dicarbamate scaffolds may inhibit other enzymes that bind nucleotide-containing substrates. PMID- 22082914 TI - Re: long-term follow-up of the treatment of renal angiomyolipomas after selective arterial embolization with alcohol. PMID- 22082915 TI - Re: gemcitabine versus bacille Calmette-Guerin after initial bacille Calmette Guerin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial. PMID- 22082916 TI - Re: a new multimodality technique accurately maps the primary lymphatic landing sites of the bladder. PMID- 22082917 TI - Re: effect of a minimum lymph node policy in radical cystectomy and pelvic lymphadenectomy on lymph node yields, lymph node positivity rates, lymph node density, and survivorship in patients with bladder cancer. PMID- 22082918 TI - Re: Risk Profiles and Treatment Patterns Among Men Diagnosed as Having Prostate Cancer and a Prostate-Specific Antigen Level Below 4.0 ng/ml. PMID- 22082919 TI - Re: the relationship between prostate-specific antigen and prostate cancer risk: the prostate biopsy collaborative group. PMID- 22082920 TI - Re: years of potential life lost caused by prostate cancer deaths in the United States-projection from 2004 through 2050. PMID- 22082921 TI - Re: comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer. PMID- 22082922 TI - Re: impact of common medications on serum total prostate-specific antigen levels: analysis of the national health and nutrition examination survey. PMID- 22082923 TI - Re: Prevalence and Impact of Bacteriuria and/or Urinary Tract Infection in Interstitial Cystitis/Painful Bladder Syndrome. PMID- 22082924 TI - Re: Malignant Renal Cysts: Diagnostic Performance and Strong Predictors at MDCT. PMID- 22082925 TI - Re: Use of Inverted Fluoroscope's C-Arm During Endoscopic Treatment of Urinary Tract Obstruction in Pregnancy: A Practicable Solution to Cut Radiation. PMID- 22082926 TI - Re: multicenter experience with metallic ureteral stents for malignant and chronic benign ureteral obstruction. PMID- 22082927 TI - Re: Complications of the AdVance Transobturator Male Sling in the Treatment of Male Stress Urinary Incontinence. PMID- 22082928 TI - Re: penoscrotal plication as a uniform approach to reconstruction of penile curvature. PMID- 22082929 TI - Re: clinical experience in a modified roux-y-shaped sigmoid neobladder: assessment of complications and voiding patterns in 43 patients. PMID- 22082930 TI - Re: antagonists of growth hormone-releasing hormone inhibit the proliferation of human benign prostatic hyperplasia cells. PMID- 22082931 TI - Re: Long-Term Treatment and Prognostic Factors of alpha1-Blockers for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: A Pilot Study Comparing Naftopidil and Tamsulosin Hydrochloride. PMID- 22082932 TI - Re: effects of age on levator function and morphometry of the levator hiatus in women with pelvic floor disorders. PMID- 22082933 TI - Re: prevalence and correlates of nocturia in community-dwelling older adults. PMID- 22082934 TI - Re: lessons learned: impact of a continence promotion activity for older community-dwelling women. PMID- 22082935 TI - Re: randomized trial of transcutaneous tibial nerve stimulation to treat urge urinary incontinence in older women. PMID- 22082936 TI - Re: Effect of Sexual Function on Health-Related Quality of Life Mediated by Depressive Symptoms in Cardiac Rehabilitation. Findings of the SPARK Project in 493 Patients. PMID- 22082937 TI - Re: persistent sexual dysfunction impairs quality of life after cardiac transplantation. PMID- 22082938 TI - Re: A Low Intake of Antioxidant Nutrients is Associated With Poor Semen Quality in Patients Attending Fertility Clinics. PMID- 22082939 TI - Re: testicular spermatozoa have statistically significantly lower DNA damage compared with ejaculated spermatozoa in patients with unsuccessful oral antioxidant treatment. PMID- 22082940 TI - Re: soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence. PMID- 22082941 TI - Re: a novel application of 1H magnetic resonance spectroscopy: non-invasive identification of spermatogenesis in men with non-obstructive azoospermia. PMID- 22082942 TI - Re: cystic dysplasia of the rete testis: a case of spontaneous regression and review of published reports. PMID- 22082943 TI - Re: our initial experience with the technique of complete primary repair for bladder exstrophy. PMID- 22082944 TI - Re: renal impairment in children with cystic fibrosis. PMID- 22082945 TI - Re: reconstitution of experimental neurogenic bladder dysfunction using skeletal muscle-derived multipotent stem cells. PMID- 22082946 TI - Re: Innervation of Reconstructed Bladder Above the Level of Spinal Cord Injury for Inducing Micturition by Contractions of the Abdomen-to-Bladder Reflex Arc. PMID- 22082947 TI - Biliary atresia in the Netherlands: outcome of patients diagnosed between 1987 and 2008. AB - OBJECTIVE: To examine the outcome of biliary atresia (BA) and to identify prognostic factors using a national database. STUDY DESIGN: All children born between January 1987 and December 2008 who underwent the Kasai surgical procedure for BA were retrieved from the Netherlands Study Group on Biliary Atresia Registry database. Outcomes were measured in terms of clearance of jaundice (bilirubin <1.17 g/dL, or 20 MUmol/L, within 6 months after surgery) and 4-year transplant-free survival. Two cohorts, one from 1987-1997 and the other from 1998 2008, were compared. Survival rates were determined using Kaplan-Meier analysis, and prognostic factors were tested with univariate and multivariate analyses. RESULTS: Between January 1987 and December 2008, 214 patients underwent Kasai surgery for BA. In this series, the 4-year transplant-free survival was 46%+/-4%, and 4-year overall survival was 73%+/-3%. Clearance of jaundice, surgery within 60 days, and postoperative antibiotic prophylaxis use were independently associated with increased transplant-free survival. The yearly caseload per center (range, 0.5-2.1) was not correlated with transplant-free survival (r=0.024; P=.73). CONCLUSION: During the past 2 decades, outcome parameters have remained constant and are comparable with those reported from other Western countries, despite a relatively low annual caseload per center. Timely surgical correction and postoperative antibiotic therapy were associated with a higher transplant-free survival rate. PMID- 22082948 TI - Hypertension in a girl with severe coarctation of the aorta and renal agenesis. PMID- 22082949 TI - Non-blood group-specific red blood cell transfusions in preterm infants and necrotizing enterocolitis. PMID- 22082951 TI - Blood pressure in pediatric chronic kidney disease--it's in the ears of the beholder. PMID- 22082952 TI - Hip ultrasounds: where do we go from here? PMID- 22082953 TI - Longitudinal, three-dimensional analysis of head shape in children with and without deformational plagiocephaly or brachycephaly. AB - OBJECTIVES: To assess 3-dimensional (3D) changes in head shape in infancy and at age 18 months in children with and without plagiocephaly or brachycephaly. STUDY DESIGN: Using a longitudinal design, we evaluated head shape using 3D surface imaging. We compared the head shapes of children with (1) diagnosed deformational plagiocephaly or brachycephaly (cases; n=233); (2) unaffected controls, with no evidence of dysmorphology (n=167); and (3) affected controls, who despite having no previous diagnosis demonstrated skull dysmorphology on 3D surface imaging (n=70). RESULTS: Cases had greater skull flattening and asymmetry than unaffected controls at both time points, as did controls with skull dysmorphology. In all groups, head shapes became less flat and more symmetric over time. Among cases, symmetry improved slightly more for those who received orthotic treatment. CONCLUSIONS: Although head shape improves over time for children with deformational plagiocephaly or brachycephaly, skull dysmorphology persists relative to unaffected controls. Further research is needed to clarify the extent to which these differences are detectable to clinicians and lay observers. PMID- 22082955 TI - Development and validation of educational materials for food allergy. AB - OBJECTIVE: To develop and validate a food allergy educational program. STUDY DESIGN: Materials developed through focus groups and parental and expert review were submitted to 60 parents of newly referred children with a prior food allergy diagnosis and an epinephrine autoinjector. The main outcome was correct demonstration of an autoinjector. RESULTS: The correct number of autoinjector activation steps increased from 3.4 to 5.95 (of 6) after training (P < .001) and was 5.47 at 1 year (P < .05). The mean score for comfort with using the autoinjector (7-point Likert scale) before the curriculum was 4.63 (somewhat comfortable) and increased to 6.23 after the intervention (P < .05) and remained elevated at 1 year (6.03). Knowledge tests (maximum 15) increased from a mean score of 9.2 to 12.4 (P < .001) at the initial visit and remained at 12.7 at 1 year. The annualized rate of allergic reactions fell from 1.77 (historical) the year prior, to 0.42 (P < .001) after the program. On a 7-point Likert scale, all satisfaction categories remained above a favorable mean score of 6: straight forward, organized, interesting, relevant, and recommend to others. CONCLUSIONS: This food allergy educational curriculum for parents, now available online at no cost, showed high levels of satisfaction and efficacy. PMID- 22082956 TI - Radiotherapy as a risk factor for malignant melanoma after childhood skin hemangioma. AB - The aim of this study was to determine therapy-related risk factors for the development of melanoma after hemangioma. A cohort study was conducted among 4620 patients treated before 16 years of age for skin hemangioma in France. A nested case-control study was also conducted on 13 patients who developed a melanoma (cases) matched with five controls in cohort according to sex, age at the hemangioma diagnostic, the calendar year of occurrence of the hemangioma, and follow-up. The radiation dose received at the site of the melanoma and at the same site in controls was estimated, and named 'local dose'. A total of 13 melanomas were registered during an average follow-up of overall 35 years, the risk of developing melanoma after a hemangioma treatment was 2.5-fold higher [95% confidence interval (CI): 1.4-4.1] compared with that of the general population, this ratio being only 0.8 (95% CI: 0.05-3.6) in 896 patients who did not receive radiotherapy, but 3.0 (95% CI: 1.6-5.1) after radiotherapy. When adjusting on sex, age, and year of the treatment and follow-up duration, melanoma risk was 11.9 (95% CI: 1.4-123) times higher in patients treated with ytrium 90 than in the ones who did not received radiotherapy. In the case-control study, the risk of melanoma was not linked to the local radiation dose. Indeed, the increase in melanoma risk was observed even for very low local doses. Compared with the corresponding skin areas in patients who did not receive radiotherapy, the ones having received less than 0.001 Gy had a melanoma risk of 3.9 (95% CI: 0.5-32) and those who received more than 0.01 Gy had a risk of 6.9 (0.5-99). This study suggests that radiation therapy of skin hemangioma increases the risk of further melanoma, but we were not able to evidence a relation with the local dose. Nevertheless, childhood treated for hemangioma should be considered at risk for developing melanoma and suspicious pigmented lesions should be carefully evaluated even far from treated areas. PMID- 22082957 TI - Regional lymphatic immunity in melanoma. AB - Melanoma is an immunogenic tumor that has developed methods to successfully evade immune recognition, while paradoxically spreading through the lymphatic system. Increasing evidence supports that melanoma-derived factors suppress regional immunity within the host. At a very early stage, melanoma communicates with the tumor-draining lymph nodes, and prepares them for seeding of metastatic disease by stimulating lymphangiogenesis and downregulation of the sentinel lymph node immunity well before the malignant cells arrive. Investigations have demonstrated that the induction of suppressor cells, peripheral tolerance, and a less tumor responsive Th2 cytokine environment may provide a hospitable environment for subsequent lymphatic metastasis. Patients with early-stage disease may benefit from the restoration of the regional immune function to a level that controls the progression of residual occult metastases and ensures a durable clinical response. Herein we provide a succinct summary of the current progress in this field in order to guide future investigations. PMID- 22082958 TI - Listeria and autophagy escape: involvement of InlK, an internalin-like protein. AB - Autophagy is a cell-autonomous mechanism of innate immunity that protects the cytosol against bacterial infection. Invasive bacteria, including Listeria monocytogenes, have thus evolved strategies to counteract a process that limits their intracellular growth. ActA is a surface protein produced by L. monocytogenes to polymerize actin and mediate intra- and intercellular movements, which plays a critical role in autophagy escape. We have recently investigated the role of another L. monocytogenes surface protein, the internalin InlK, in the infection process. We showed that in the cytosol of infected cells, InlK interacts with the Major Vault Protein (MVP), the main component of cytoplasmic ribonucleoprotein particles named vaults. Although MVP has been implicated in a variety of key cellular process, its role remains elusive. We demonstrated that L. monocytogenes is able, via InlK, to decorate its surface with MVP in order to escape autophagic recognition. Strikingly, this new strategy used by L. monocytogenes to avoid autophagy is independent of ActA, suggesting that InlK-MVP interactions and actin polymerization are two processes that favor in the same manner the infection process. Understanding the role of MVP may provide new insights into bacterial infection and autophagy. PMID- 22082959 TI - Pro-tumorigenic function of autophagy in mammary oncogenesis. AB - Autophagy is a highly conserved catabolic cellular process by which cells degrade intracellular constituents in lysosomes, and its dysfunctions have been associated with a variety of human diseases including cancer. Previous studies have linked autophagy to both tumor-suppressive and promoting functions in different contexts, although the pro-tumorigenic function of autophagy has not been examined directly in breast or other cancers in animal models with intact immune functions in vivo. FIP200 (focal adhesion kinase family interacting protein of 200 kD) is a component of the ULK1-Atg13-FIP200-Atg101 complex that is essential for the induction of mammalian autophagy. In our recent study, we show that conditional knockout (KO) of FIP200 in the well-characterized MMTV-PyMT mouse model of human breast cancer significantly suppresses mammary tumorigenesis and progression. Similar to a number of recent studies in Ras-transformed cells, our studies revealed the importance of autophagy in promoting tumorigenesis through regulation of tumor cell glycolysis and proliferation. In addition to the intrinsic defects in proliferation of FIP200-null tumor cells, we also showed that FIP200 deletion in mammary tumor cells triggers increased host anti-tumor immune surveillance, which also contributes to the decreased mammary tumorigenesis and progression. Our study provides the first direct demonstration of a pro-tumorigenic role of autophagy in oncogene-driven tumor models with intact immune functions in vivo. They also suggest FIP200 and other autophagy proteins as potential therapeutic targets for cancer treatment, and raise a number of questions for future studies on the potentially dual functions of autophagy in promoting and suppressing tumorigenesis under different conditions in vivo. PMID- 22082960 TI - Autophagy: a new player in hepatic stellate cell activation. AB - Hepatic stellate cell (HSC) activation, the transition from a resident quiescent HSC to a myofibroblastic collagen-producing HSC, is a fundamental feature of liver fibrosis. Autophagy has been implicated in major liver pathologies, such as HCV infection and hepatocarcinoma. However, its role in HSC biology is largely unknown. Recently, we were able to demonstrate that HSC activation is followed by an increased autophagic flux and that its inhibition can partially inhibit the HSC myofibroblastic transition. These results point to autophagy as a possible target in the prevention of HSC activation. PMID- 22082954 TI - Physical activity, fitness, and serum leptin concentrations in adolescents. AB - OBJECTIVE: To examine the association of physical activity and fitness with leptin concentrations in European adolescents, after taking into account several potential confounders including total body fat (TBF). STUDY DESIGN: We conducted a cross-sectional study in a school setting for the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. This study included 902 (509 girls) adolescents aged 12.5-17.5 years. Weight, height, and TBF (sum of 6 skinfold thickness) were measured, and fat free mass and body mass index were calculated. Physical activity was assessed by accelerometry. Physical fitness was assessed by the handgrip, standing long jump, 4 * 10-m shuttle run, and 20-m shuttle run tests. Serum fasting leptin, insulin, and glucose concentrations were measured, and homeostasis model assessment was computed. Multiple linear regression models were used. RESULTS: Vigorous physical activity and fitness tests (all P < .05) were negatively associated with leptin, independently of several confounders including TBF and homeostasis model assessment. These associations remained significant after further controlling for each other (physical activity and fitness). CONCLUSION: These results suggest that vigorous physical activity and fitness moderate the levels of leptin concentrations, regardless of relevant confounders including TBF. Intervention programs addressed to increase high intensity physical activity and fitness as well as to assess its impact on leptin concentration are required. PMID- 22082962 TI - Circadian regulation of autophagy rhythm through transcription factor C/EBPbeta. AB - Temporal organization of nutrient and energy metabolism is important for maintaining homeostasis in mammals. Autophagy is a conserved cellular pathway that is activated in response to nutrient limitation, resulting in the degradation of cytoplasmic components and the release of amino acids and other nutrients. Recently, we reported that autophagy exhibits robust circadian rhythm in mouse liver, accompanied by cyclic induction of genes involved in various steps of autophagy. Rhythmic activation of physiological autophagy appears to be regulated by transcription factor C/EBPbeta, which is sufficient and required for nutritional and circadian regulation of autophagy gene expression. These findings provide new insight into transcriptional control of autophagy and reveal a potentially important role of autophagy cycles in metabolic homeostasis. PMID- 22082961 TI - Vid30 is required for the association of Vid vesicles and actin patches in the vacuole import and degradation pathway. AB - When Saccharomyces cerevisiae is starved of glucose, the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase (MDH2), isocitrate lyase (Icl1) and phosphoenolpyruvate carboxykinase (Pck1) are induced. However, when glucose is added to prolonged starved cells, these enzymes are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. Recent evidence suggests that the Vid pathway merges with the endocytic pathway at actin patches where endocytic vesicles are formed. The convergence of the Vid pathway with the endocytic pathway allows cells to remove intracellular and extracellular proteins simultaneously. However, the genes that regulate this step of the convergence have not been identified previously. Here we show that VID30 plays a critical role for the association of Vid vesicles and actin patches. Vid30 is constitutively expressed and interacts with Vid vesicle proteins Vid24 and Sec28 but not with the cargo protein FBPase. In the absence of SEC28 or VID24, Vid30 association with actin patches was prolonged. In cells lacking the VID30 gene, FBPase and Vid24 were not localized to actin patches, suggesting that Vid30 has a role in the association of Vid vesicles and actin patches. Vid30 contains a LisH and a CTLH domain, both of which are required for FBPase degradation. When these domains were deleted, FBPase trafficking to the vacuole was impaired. We suggest that Vid30 also has a role in the Vid pathway at a later step in a process that is mediated by the LisH and CTLH domains. PMID- 22082964 TI - The end of autophagic cell death? AB - In the mammalian system, cell death is often preceded or accompanied by autophagic vacuolization, a finding that initially led to the widespread belief that so-called "autophagic cell death" would be mediated by autophagy. Thanks to the availability of genetic tools to disable the autophagic machinery, it has become clear over recent years that autophagy usually constitutes a futile attempt of dying cells to adapt to lethal stress rather than a mechanism to execute a cell death program. Recently, we systematically addressed the question as to whether established or prospective anticancer agents may induce "autophagic cell death". Although a considerable portion among the 1,400 compounds that we evaluated induced autophagic puncta and actually increased autophagic flux, not a single one turned out to kill tumor cells through the induction of autophagy. Thus, knockdown of essential autophagy genes (such as ATG5 and ATG7) failed to prevent and rather accelerated chemotherapy-induced cell death, in spite of the fact that this manipulation efficiently inhibits autophagosome formation. Herein, we review these finding and--polemically--raise doubts as to the very existence of "autophagic cell death". PMID- 22082963 TI - DRAM-1 encodes multiple isoforms that regulate autophagy. AB - Macro(autophagy) is a cellular mechanism which delivers cytoplasmic constituents to lysosomes for degradation. Due to its role in maintaining cellular integrity, autophagy protects against various diseases including cancer. p53 is a major tumor suppressor gene which can modulate autophagy both positively and negatively. p53 induces autophagy via transcriptional activation of Damage Regulated Autophagy Modulator (DRAM-1). We report here that DRAM-1 encodes not just one mRNA, but a series of p53-inducible splice variants which are expressed at varying levels in multiple human and mouse cell lines. Two of these new splice variants, termed SV4 and SV5, result in mature mRNA species. Different to 'full length' DRAM-1 (SV1), SV4 and SV5 do not localise to lysosomes or endosomes, but instead partially localise to peroxisomes and autophagosomes respectively. In addition, SV4 and SV5 can also be found co-localised with certain markers of the endoplasmic reticulum. Similar to SV1, SV4 and SV5 do not appear to be inducers of programmed cell death, but they do modulate autophagy. In summary, these findings identify new autophagy regulators that provide insight into the control of autophagy downstream of p53. PMID- 22082965 TI - Propagation direction of natural mechanical oscillations in the biceps brachii muscle during voluntary contraction. AB - The aim of the study was to determine the directionality of the coupling of mechanical vibrations across the biceps brachii muscle at different frequencies of interest during voluntary contraction. The vibrations that are naturally generated by skeletal muscles were recorded by a two-dimensional array of skin mounted accelerometers over the biceps brachii muscle (surface mechanomyogram, S MMG) during voluntary isometric contractions in ten healthy young men. As a measure of the similarity of vibration between a given pair of accelerometers, the spatial coherence of S-MMG at low (f<25Hz) and high (f>25Hz) frequency bands were investigated to determine if the coupling of the natural mechanical vibrations were due to the different physiological muscle activity at low and high frequencies. In both frequency bands, spatial coherence values for sensor pairs aligned longitudinally along the proximal to distal ends of the biceps were significantly higher compared with those for the sensor pairs oriented perpendicular to the muscle fibers. This difference was more evident at the higher frequency band. The findings indicated that coherent mechanical oscillations mainly propagated along the longitudinal direction of the biceps brachii muscle fibers at high frequencies (f>25Hz). PMID- 22082966 TI - A protocol for computer-based protein structure and function prediction. AB - Genome sequencing projects have ciphered millions of protein sequence, which require knowledge of their structure and function to improve the understanding of their biological role. Although experimental methods can provide detailed information for a small fraction of these proteins, computational modeling is needed for the majority of protein molecules which are experimentally uncharacterized. The I-TASSER server is an on-line workbench for high-resolution modeling of protein structure and function. Given a protein sequence, a typical output from the I-TASSER server includes secondary structure prediction, predicted solvent accessibility of each residue, homologous template proteins detected by threading and structure alignments, up to five full-length tertiary structural models, and structure-based functional annotations for enzyme classification, Gene Ontology terms and protein-ligand binding sites. All the predictions are tagged with a confidence score which tells how accurate the predictions are without knowing the experimental data. To facilitate the special requests of end users, the server provides channels to accept user-specified inter-residue distance and contact maps to interactively change the I-TASSER modeling; it also allows users to specify any proteins as template, or to exclude any template proteins during the structure assembly simulations. The structural information could be collected by the users based on experimental evidences or biological insights with the purpose of improving the quality of I-TASSER predictions. The server was evaluated as the best programs for protein structure and function predictions in the recent community-wide CASP experiments. There are currently >20,000 registered scientists from over 100 countries who are using the on-line I-TASSER server. PMID- 22082967 TI - Is there still a place for LASER technology in modern neurosurgery? PMID- 22082968 TI - In situ reconstruction of parietal bone craniectomy after convexity meningioma resection. PMID- 22082969 TI - Pituitary carcinoma. PMID- 22082970 TI - Is it useful to administer routine antihelminthic therapy after the resection of intraventricular cysticercosis? PMID- 22082971 TI - A pathway to endoscopic bariatric therapies. AB - The American Society for Gastrointestinal Endoscopy (ASGE) is dedicated to advancing patient care and digestive health by promoting excellence in gastrointestinal endoscopy. The American Society for Metabolic and Bariatric Surgery (ASMBS) is dedicated to improving public health and well-being by lessening the burden of the disease of obesity and related diseases. They are the largest professional societies for their respective specialties of gastrointestinal endoscopy and bariatric surgery in the world. The ASGE/ASMBS task force was developed to collaboratively address opportunities for endoscopic approaches to obesity, reflecting the strengths of our disciplines, to improve patient and societal outcomes. This white paper is intended to provide a framework for, and a pathway towards, the development, investigation, and adoption of safe and effective endoscopic bariatric therapies (EBT). PMID- 22082975 TI - Temporal variation and provenance of thorium deposition observed at Tsukuba, Japan. AB - Temporal variations of monthly thorium (Th) deposition observed at Tsukuba, Japan during the period 1990-2007, comparing with plutonium deposition, was studied. The monthly (232)Th deposition as did (239,240)Pu, varied according to season and inter-annually. In particular, (232)Th deposition increased significantly in spring coinciding with Asian dust (Kosa) events. The (230)Th/(232)Th activity ratios vary according to sources and can therefore be used to differentiate between locally derived and remotely derived (232)Th. The (230)Th/(232)Th activity ratios in deposition samples showed large variability with high ratios occurring in early spring. These high (230)Th/(232)Th ratios in deposition can be attributed to local dust storms, especially in early spring, that cause resuspension of soils from cultivated fields which are characterized by high (230)Th/(232)Th activity ratios. The results reveal that both locally and remotely derived (232)Th deposition showed seasonal variations with maxima in spring, although the remotely derived fraction is dominant rather than the locally derived one. The (232)Th deposition maxima later in spring is attributable to the remotely derived fraction, corresponding to the Kosa events. Annual (232)Th deposition exhibited an increasing trend, suggesting the presence of sources other than soil dust such as fly ash from increasing coal burning. PMID- 22082976 TI - Please close this skin wound. AB - Acute cutaneous wounds following trauma are commonly encountered in the emergency department. This article explains the principles of their closure and provides advice on optimal management. Wound healing occurs in four phases: haemostatic, inflammatory, proliferative and maturation (Janis et al, 2010). The guidance below is based on the authors' personal practice, designed to promote transition through these stages and result in optimized healing with minimal scarring. It is intended to guide the reader through what can be a daunting prospect for many doctors in training: the acute closure of simple wounds. PMID- 22082977 TI - Splenomegaly. AB - Splenomegaly is a common finding on clinical examination, and frequently features in postgraduate assessments. The spleen does not normally descend below the left costal margin. The routine abdominal examination will identify whether the spleen is palpable, and if so splenomegaly is almost universally present. This is generally pathological and warrants investigation. PMID- 22082978 TI - Pregnancy and the liver. AB - In pregnancy the liver can be affected by diseases specific to pregnancy as well as unrelated conditions. The possible effect of the disease and its management on both the fetus and mother must be considered. Several physiological changes occur during pregnancy as liver metabolism is altered. Serum protein concentrations fall, with a decrease in serum albumin in part the result of the dilutional effect of an increase in plasma volume. Alanine transaminase and aspartate transaminase levels decrease (Table 1), complicating the diagnosis of disorders involving subtle changes in liver function. Alkaline phosphatase is also produced by the placenta, making this an unreliable marker of liver dysfunction in pregnancy. PMID- 22082979 TI - Management and prognosis of multiple sclerosis. AB - Multiple sclerosis is a common disease of the CNS. The first of these articles (Hassan-Smith and Douglas, 2011) examined its epidemiology and diagnosis. This article explores the management and prognosis of multiple sclerosis, including the rapidly evolving field of disease-modifying therapeutics. However, equally important is the management of problems related to chronic multiple sclerosis and knowledge of which symptomatic treatments may be helpful. Finally, the prognosis is discussed; vital when counselling newly diagnosed patients. PMID- 22082980 TI - Evaluation of global left ventricular systolic function using three-dimensional echocardiography speckle-tracking strain parameters. AB - BACKGROUND: The aim of this study was to evaluate the capacity and reproducibility of three-dimensional echocardiographic (3DE) strain parameters in the assessment of global left ventricular (LV) systolic function. METHODS: A total of 128 subjects with differing LV ejection fractions were investigated using two-dimensional echocardiographic (2DE) and 3DE strains. Three-dimensional echocardiographic strain allows obtaining longitudinal, circumferential, radial, and area strains. First, values of global longitudinal strain (GLS) by 2DE and 3DE speckle-tracking analyses were compared. Thereafter, 3DE strain parameters were correlated with LV ejection fraction and indexed output. Last, the variability of 3DE versus 2DE strain measurements as well as recorded time of analysis were assessed. RESULTS: After excluding 21 patients for insufficient image quality, four for arrhythmia, two for severe valvular disease, and one for severe dyspnea, the final population consisted of 100 patients. Comparison between 2DE and 3DE GLS revealed high correspondence (r = 0.91, y = 1.04x - 0.71) and mean error measurement of -1.3% (95% confidence interval, -5.7 to 3.2). Among strain parameters, global area strain exhibited the highest correlation with LV ejection fraction (y = -1.65 + 10.4, r = -0.92, P < .001). Intraobserver measurement variability proved acceptable: 8% for GLS (vs 6% on 2DE analysis), 7% for circumferential strain (vs 15% on 2DE analysis), 7% for radial strain (vs 33% on 2DE analysis), and 5% for global area strain. The mean error between two measurements was lower with 3DE than 2DE analysis for circumferential and radial strains but similar for GLS. The mean time of analysis was of 117 +/- 16 sec for 3DE analysis, which was 25% less than for 2DE analysis (P < .001). CONCLUSIONS: Of all strain parameters, new 3DE area strain correlated best with common LV systolic function parameters and is thus the most promising approach, while all 3DE strain markers exhibited good reproducibility. PMID- 22082981 TI - Elective oocyte cryopreservation: who should pay? AB - Despite the initial reactions of disapproval, more and more fertility clinics are now offering oocyte cryopreservation to healthy women in order to extend their reproductive options. However, so-called social freezing is not placed on an equal footing with 'regular' IVF treatments where public funding is concerned. In those countries or states where IVF patients receive a number of free cycles, we argue that fertilization and transfer cycles of women who proactively cryopreserved their oocytes should be covered. Moreover, when the argument of justice is consistently applied, coverage should also include the expenses of ovarian stimulation, oocyte retrieval and storage. Different modalities are possible: full coverage from the onset, reimbursement in cash or reimbursement in kind, by offering more free transfer cycles. PMID- 22082982 TI - The efficiency of male fertility restoration is dependent on the recovery kinetics of spermatogonial stem cells after cytotoxic treatment with busulfan in mice. AB - BACKGROUND: Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis and represent a crucial resource for male fertility restoration. It has not been well documented, however, whether the recovery of SSC population size after cytotoxic damage associates with the kinetics of male fertility restoration. We addressed this issue using the mouse as a model. METHODS: Following single injections of busulfan at 15, 30 or 45 mg/kg into male mice, we examined their ability to sire offspring at different times by natural mating and determined SSC numbers using spermatogonial transplantation. We measured testis physiological parameters (testis weights, sperm counts, serum and intratesticular testosterone levels, and histological assessments of spermatogenic recovery) and quantified the expression of glial-cell-line-derived neurotrophic factor (GDNF) transcripts. RESULTS: Regardless of busulfan doses, fertility was lost within 4 weeks after treatment, while more than 95% of SSCs were lost within 3 days. Fertility and SSC numbers gradually recovered with time, but the recoveries were delayed at higher busulfan doses. Interestingly, SSC numbers reached ~30% of before-treatment levels by 4 weeks prior to the time of fertility restoration, across the dose groups. Sperm counts were ~20% of before-treatment levels at the onset of fertility restoration, regardless of busulfan doses. We detected a significant increase in total GDNF mRNA per testis immediately after busulfan treatment. CONCLUSIONS: The loss and restoration of fertility after busulfan treatment are direct consequences of SSC loss and expansion. Our data suggest that there is a threshold in SSC numbers that allows for male fertility restoration and that the testicular somatic environment responds rapidly and temporarily to the loss of spermatogonia, including SSCs, by altering GDNF mRNA levels. This study provides fundamental information to clinically apply SSCs for male fertility restoration in the future. PMID- 22082983 TI - Overexpression of receptor for advanced glycation end products induces monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cell line. AB - AIM: The receptor for advanced glycation end-products (RAGE) has been suggested to play a pivotal role in the development of diabetic vasculopathy and atherosclerosis; however, due to its low expression, the physiological role of RAGE in vascular smooth muscle cells (VSMC) remains unknown. METHODS: Using VSMC lines stably expressing RAGE (RAGE-A10), we studied the molecular mechanism by which S100B, a RAGE ligand, induces proinflammatory gene expression. RESULTS: S100B induced NF-kappaB activation and the expression of several proinflammatory genes (MCP-1, IL-6, ICAM-1) at mRNA and protein levels in RAGE-A10, among which MCP-1 expression was the most robust. S100B-induced MCP-1 expression was dose dependently blocked by inhibitors of JNK (SP600125), p38 (SB203580), MEK-1 (U0126) as well as NF-kappaB (Bay117085). In RAGE-A10, S100B activated JNK, MEK-1 and p38. S100B-induced MCP-1 promoter activity via NF-kappaB binding sites and nuclear translocation of NF-kappaB p65 subunit were blocked by SP600125, U0126, and SB203580 in RAGE-A10. CONCLUSION: Our study demonstrates that S100B increased MCP-1 expression via NF-kappaB and mitogen-activated protein kinase (JNK, ERK1/2, and p38) pathways in RAGE-overexpressed A10 cell lines. Thus, RAGE-A10 could be a useful cell model for studying the molecular mechanism(s) of up-regulated RAGE in the vasculature. PMID- 22082984 TI - Studying cell behavior in whole zebrafish embryos by confocal live imaging: application to hematopoietic stem cells. AB - Confocal live imaging is a key tool for studying cell behavior in the whole zebrafish embryo. Here we provide a detailed protocol that is adaptable for imaging any progenitor cell behavior in live zebrafish embryos. As an example, we imaged the emergence of the first hematopoietic stem cells from the aorta. We discuss the importance of selecting the appropriate zebrafish transgenic line as well as methods for immobilization of embryos to be imaged. In addition, we highlight the confocal microscopy acquisition parameters required for stem cell imaging and the software tools we used to analyze 4D movies. The whole protocol takes 2 h 15 min and allows confocal live imaging from a few hours to several days. PMID- 22082985 TI - Chromatin immunoprecipitation and high-throughput sequencing from paraffin embedded pathology tissue. AB - Formalin-fixed, paraffin-embedded (FFPE) samples represent the gold standard for storage of pathology samples. Here we describe pathology tissue chromatin immunoprecipitation (PAT-ChIP), a technique for extraction and high-throughput analysis, by techniques such as ChIP-seq, of chromatin derived from FFPE samples. Technically, the main challenge of PAT-ChIP is the preparation of good-quality chromatin from FFPE samples. Here we provide a detailed explanation of the methodology used, the choice of reagents and the troubleshooting steps required to establish a robust chromatin preparation procedure. Other steps have also been adapted from existing techniques to optimize their use for PAT-ChIP-seq. The protocol requires 4 d from the start to the end of the PAT-ChIP procedure. PAT ChIP provides, for the first time, the chance to perform analyses of histone modifications and transcription factor binding on a genome-wide scale using patient-derived FFPE samples. This technique therefore allows the immediate use of pathology archives (even those that are several years old) for epigenetic analyses and the identification of candidate epigenetic biomarkers or targets. PMID- 22082986 TI - Generating human intestinal tissue from pluripotent stem cells in vitro. AB - Here we describe a protocol for generating 3D human intestinal tissues (called organoids) in vitro from human pluripotent stem cells (hPSCs). To generate intestinal organoids, pluripotent stem cells are first differentiated into FOXA2(+)SOX17(+) endoderm by treating the cells with activin A for 3 d. After endoderm induction, the pluripotent stem cells are patterned into CDX2(+) mid- and hindgut tissue using FGF4 and WNT3a. During this patterning step, 3D mid- or hindgut spheroids bud from the monolayer epithelium attached to the tissue culture dish. The 3D spheroids are further cultured in Matrigel along with prointestinal growth factors, and they proliferate and expand over 1-3 months to give rise to intestinal tissue, complete with intestinal mesenchyme and epithelium comprising all of the major intestinal cell types. To date, this is the only method for efficiently directing the differentiation of hPSCs into 3D human intestinal tissue in vitro. PMID- 22082988 TI - Efficacy of pregabalin in a case of stiff-person syndrome: clinical and neurophysiological evidence. AB - Symptomatic treatment of stiff-person syndrome (SPS) might be challenging and a significant improvement of stiffness and rigidity is generally reached with high doses of benzodiazepines or baclofen causing side effects. A 71-year old woman diagnosed with SPS complained of marked stiffness of trunk and lower limb muscles with sudden painful spasms. She was unable to walk and she could not lean on her right leg. Cortical silent period (CSP) duration evaluated from right abductor pollicis brevis (APB) with transcranial magnetic stimulation was shortened. Polygraphic electromyographic (EMG) evaluation from paraspinal and leg muscles disclosed continuous motor unit activity at rest with interference muscular pattern. Symptomatic treatment with diazepam was withdrawn because of excessive sedation. In order to relieve the intense lumbar pain, she was prescribed pregabalin; since the day after, rigidity and painful spasms dramatically improved and she could walk without assistance. The clinical benefit persisted at 3 months follow-up and was paralleled by almost complete disappearance of EMG activity at rest and prolongation of CSP. The clinical and electrophysiological data in this SPS patient suggest the possible efficacy of pregabalin as symptomatic treatment without any significant side effects, which needs to be replicated in larger case series. PMID- 22082987 TI - Measuring and interpreting point spread functions to determine confocal microscope resolution and ensure quality control. AB - This protocol outlines a procedure for collecting and analyzing point spread functions (PSFs). It describes how to prepare fluorescent microsphere samples, set up a confocal microscope to properly collect 3D confocal image data of the microspheres and perform PSF measurements. The analysis of the PSF is used to determine the resolution of the microscope and to identify any problems with the quality of the microscope's images. The PSF geometry is used as an indicator to identify problems with the objective lens, confocal laser scanning components and other relay optics. Identification of possible causes of PSF abnormalities and solutions to improve microscope performance are provided. The microsphere sample preparation requires 2-3 h plus an overnight drying period. The microscope setup requires 2 h (1 h for laser warm up), whereas collecting and analyzing the PSF images require an additional 2-3 h. PMID- 22082990 TI - Movement-related neuromagnetic fields and performances of single trial classifications. AB - In order to clarify whether neurophysiological profiles affect the performance of brain machine interfaces (BMI), we examined the relationships between amplitudes of movement-related cortical fields (MRCFs) and decoding performances during movement. Neuromagnetic activities were recorded in nine healthy participants during three types of unilateral upper limb movements. The movement types were inferred by a support vector machine. The amplitude of MRCF components, motor field (MF), movement-evoked field I (MEFI), and movement-evoked field II (MEFII) were compared with the decoding accuracies in all participants. Decoding accuracies at the latencies of MF, MEFI, and MEFII surpassed the chance level in all participants. In particular, accuracies at MEFI and MEFII were significantly higher in comparison with that of MF. The amplitudes and decoding accuracies were strongly correlated (MF, r(s)=0.90; MEFI, r(s)=0.90; and MEFII, r(s)=0.87). Our results show that the variation of MRCF components among participants reflects decoding performance. Neurophysiological profiles may serve as a predictor of individual BMI performance and assist in the improvement of general BMI performance. PMID- 22082989 TI - Specific knockdown of the D2 long dopamine receptor variant. AB - Dopamine signaling in the nucleus accumbens is critical in mediating the effects of cocaine. There are two splice variants of dopamine D2 receptors, D2L and D2S, which are believed to have different functional roles. Here, we show, that knocking down D2L selectively using viral-mediated short-hairpin RNA led to a slight but significant decrease in basal locomotor activity with no significant change in cocaine-induced stimulation of locomotion. The knockdown appears to produce a trend of reduced conditioned place preference to cocaine but the difference was not statistically significant. Our results demonstrated that the splice variants of D2 receptors can be selectively manipulated in vivo in specific brain regions allowing more specific studies of each D2 receptor isoform. PMID- 22082991 TI - Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC). AB - OBJECTIVE: To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery. METHODS: 90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008. RESULTS: Median age at time of surgery for bowel obstruction was 57 years (range, 26 to 85 years). All patients had received at least one line of platinum-based chemotherapy. Median time from diagnosis of primary disease to documented bowel obstruction requiring surgery was 19.5 months (range, 29 days-14 years). Median interval from date of completed course of chemotherapy preceding surgery for bowel obstruction was 3.8 months (range, 5 days-14 years). Ascites was present in 38/90(42%). 49/90(54%) underwent emergency surgery for bowel obstruction. The operative mortality and morbidity rates were 18% and 27%, respectively. Successful palliation, defined as adequate oral intake at least 60 days postoperative, was achieved in 59/90(66%). Only the absence of ascites was identified as a predictor for successful palliation (p=0.049). The median overall survival (OS) was 90.5 days (range, <1 day-6 years). Optimal debulking, treatment free interval (TFI) and elective versus emergency surgery did not predict survival or successful palliation from surgery for bowel obstruction (p>0.05). CONCLUSION: Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites. PMID- 22082993 TI - Indoor air pollution from gas cooking and infant neurodevelopment. AB - BACKGROUND: Gas cooking is a main source of indoor air pollutants, including nitrogen dioxide and particles. Because concerns are emerging for neurodevelopmental effects of air pollutants, we examined the relationship between indoor gas cooking during pregnancy and infant neurodevelopment. METHODS: Pregnant mothers were recruited between 2004 and 2008 to a prospective birth cohort study (INfancia y Medio Ambiente) in Spain during the first trimester of pregnancy. Third-trimester questionnaires collected information about the use of gas appliances at home. At age 11 to 22 months, children were assessed for mental development using the Bayley Scales of Infant Development. Linear regression models examined the association of gas cooking and standardized mental development scores (n = 1887 mother-child pairs). RESULTS: Gas cookers were present in 44% of homes. Gas cooking was related to a small decrease in the mental development score compared with use of other cookers (-2.5 points [95% confidence interval = -4.0 to -0.9]) independent of social class, maternal education, and other measured potential confounders. This decrease was strongest in children tested after the age of 14 months (-3.1 points [-5.1 to -1.1]) and when gas cooking was combined with less frequent use of an extractor fan. The negative association with gas cooking was relatively consistent across strata defined by social class, education, and other covariates. CONCLUSIONS: This study suggests a small adverse effect of indoor air pollution from gas cookers on the mental development of young children. PMID- 22082995 TI - Health effects of flooding in rural Bangladesh. AB - BACKGROUND: There is little information available on nontraumatic health risks as the result of floods, and on the factors that determine vulnerability to them (especially in low-income settings). We estimated the pattern of mortality, diarrhea, and acute respiratory infection following the 2004 floods in rural Bangladesh. METHODS: We conducted controlled interrupted time-series analysis of adverse health outcomes, from 2001 to 2007, in a cohort of 211,000 residents of the Matlab region classified as flooded or nonflooded in 2004. Ratios of mortality, diarrhea, and acute respiratory infection rates in flooded compared with nonflooded areas were calculated by week for mortality and diarrhea, and by month for acute respiratory infection. We controlled for baseline differences as well as normal seasonal patterns in the flooded and nonflooded areas. Variations in flood-related health risks were examined by age, income level, drinking-water source, latrine type, and service area. RESULTS: After fully controlling for pre flood rate differences and for seasonality, there was no clear evidence of excesses in mortality or diarrhea risk during or after flooding. For acute respiratory infection, we found no evidence of excess risk during the flood itself but a moderate increase in risk during the 6 months after the flood (relative risk = 1.25 [95% confidence interval = 1.06-1.47]) and the subsequent 18 months. CONCLUSIONS: We found little evidence of increased risk of diarrhea or mortality following the floods, but evidence of a moderate elevation in risk of acute respiratory infection during the 2 years after flooding. The discrepancies between our results and the apparent excesses for mortality and diarrhea reported in other situations, using less- controlled estimates, emphasize the importance of stringent confounder control. PMID- 22082994 TI - Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring. AB - BACKGROUND: Adequate vitamin D status in mothers during pregnancy may influence the health status of the child later in life. We assessed whether maternal circulating 25-hydroxyvitamin D (25[OH]D) concentrations in pregnancy are associated with risk of lower respiratory tract infections, wheezing, and asthma in the offspring. METHODS: Data were obtained from 1724 children of the INfancia y Medio Ambiente (INMA) Project, a population-based birth cohort study. Maternal circulating 25(OH)D concentrations were measured in pregnancy (mean gestational age = 12.6 [SD = 2.5] weeks). When the child was age 1 year, parents were asked if their child had a physician-confirmed history of lower respiratory tract infections or a history of wheezing. The questions about wheezing were repeated annually thereafter. Asthma was defined as parental report of doctor diagnosis of asthma or receiving treatment at the age of 4-6 years or wheezing since the age of 4 years. RESULTS: The median maternal circulating 25(OH)D concentration in pregnancy was 29.5 ng/mL (interquartile range, 22.5-37.1 ng/mL). After multivariable adjustment, there was a trend for an independent association between higher levels of maternal circulating 25(OH)D levels in pregnancy and decreased odds of lower respiratory tract infections in offspring (for cohort- and season-specific quartile Q4 vs. Q1, odds ratio = 0.67 [95% confidence interval = 0.50-0.90]; test for trend, P = 0.016). We found no association between 25(OH)D levels in pregnancy and risk of wheezing at age 1 year or 4 years, or asthma at age 4-6 years. CONCLUSIONS: Higher maternal circulating 25(OH)D concentrations in pregnancy were independently associated with lower risk of lower respiratory tract infections in offspring in the first year of life but not with wheezing or asthma in childhood. PMID- 22082996 TI - Cell phone use and crash risk: evidence for positive bias. AB - BACKGROUND: Recent epidemiologic studies have estimated little or no increased risk of automotive crashes related to cell phone conversations by the driver, whereas earlier case-crossover studies estimated the relative risk as close to 4. Did earlier studies introduce a positive bias in relative risk estimates by overestimating driving exposure in control windows? METHODS: Driving exposures in a "control" window and a corresponding "case" window on the subsequent day were tabulated across 100 days for 439 GPS-instrumented vehicles in the Puget Sound area during 2005-2006. RESULTS: For control windows containing at least some driving, driving exposure was about one-fourth that of case windows. Adjusting for this imbalance reduces relative risk estimates in the earlier case-crossover studies from 4 to 1. CONCLUSION: Earlier case-crossover studies likely overestimated the relative risk for cell phone conversations while driving by implicitly assuming that driving during a control window was full-time when it may have been only part-time. PMID- 22082998 TI - Functional somatic syndromes. AB - Common medical disorders that fail to achieve proportionate clinical or research attention are usually complex, hidden or stigmatized. Functional somatic syndromes are all three of these, complicated further by ongoing disagreements about terminology and diagnostic criteria. PMID- 22082999 TI - Frontline health care can be improved by bringing research into the clinic. AB - Progress in clinical research has played a huge role in the great improvements in frontline health care achieved over the last 50 years, both in general practice and in hospitals. PMID- 22082997 TI - Effects of ambient pollen concentrations on frequency and severity of asthma symptoms among asthmatic children. AB - BACKGROUND: Previous studies on the associations between ambient pollen exposures and daily respiratory symptoms have produced inconsistent results. We investigated these relationships in a cohort of asthmatic children using pollen exposure models to estimate individual ambient exposures. METHODS: Daily symptoms of wheeze, night symptoms, shortness of breath, chest tightness, persistent cough, and rescue medication use were recorded in a cohort of 430 children with asthma (age 4-12 years) in Connecticut, Massachusetts, and New York. Daily ambient exposures to tree, grass, weed, and total pollen were estimated using mixed-effects models. We stratified analyses by use of asthma maintenance medication and sensitization to grass or weed pollens. Separate logistic regression analyses using generalized estimating equations were performed for each symptom outcome and pollen type. We adjusted analyses for maximum daily temperature, maximum 8-hour average ozone, fine particles (PM2.5), season, and antibiotic use. RESULTS: Associations were observed among children sensitized to specific pollens; these associations varied by use of asthma maintenance medication. Exposures to even relatively low levels of weed pollen (6-9 grains/m(3)) were associated with increased shortness of breath, chest tightness, rescue medication use, wheeze, and persistent cough, compared with lower exposure among sensitized children on maintenance medication. Grass pollen exposures >= 2 grains/m(3) were associated with wheeze, night symptoms, shortness of breath, and persistent cough compared with lower exposure among sensitized children who did not take maintenance medication. CONCLUSION: Even low-level pollen exposure was associated with daily asthmatic symptoms. PMID- 22083001 TI - Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and new treatments. AB - Pseudomonas aeruginosa is the most problematic organism in patients with cystic fibrosis. This article reviews its pathogenic mechanisms, with particular relevance to the pathophysiology of the cystic fibrosis airway, and recent advances in therapeutic approaches. PMID- 22083002 TI - Lyme disease and the heart in the UK. AB - Heart involvement from Lyme disease is uncommon in the UK but, when it does occur, can be rapidly progressive and require intensive therapy. A history of exposure and frequently a characteristic rash (erythema migrans) are the cardinal features in diagnosis. PMID- 22083003 TI - Morbidity and mortality in schizophrenia. AB - Schizophrenia is known to increase morbidity and mortality. Physical illness in schizophrenia is influenced by a combination of genetic and environmental factors. This review highlights the multifactorial aetiology of morbidity and mortality in schizophrenia and considers the use of antipsychotics for patients with this disorder. PMID- 22083004 TI - Coexistent asymptomatic myeloma and hereditary cardiac amyloidosis: an unusual case of heart failure. AB - A 76-year-old Afro-Caribbean man presenting with heart failure was diagnosed with isolated cardiac amyloid. He had evidence of myeloma on bone marrow biopsy suggesting AL amyloid, the commonest type of systemic amyloidosis, as the underlying cause. He had no other myeloma-related organ damage. However, endocardial biopsy revealed amyloid fibrils composed of transthyretin and genetic typing established heterozygozity for the valine to isoleucine mutation at position 122 (Val122Ile). The diagnosis was therefore hereditary systemic amyloidosis as a result of a genetic transthyretin variant (ATTR) causing cardiac amyloidosis and coexistent asymptomatic myeloma. This requires symptomatic treatment of heart failure only. This article discusses a rare cause of heart failure and uses this case to illustrate that histological confirmation of the amyloid-causing protein is essential. Mistaken assumption of AL amyloid could have resulted in inappropriate cytotoxic therapy targeting the plasma cell clone. PMID- 22083005 TI - Positron emission tomography computed tomography in oncology. AB - The role of positron emission tomography computed tomography in oncological imaging has rapidly evolved. It has proven itself to be cost effective and alters patient management in a significant proportion of cases. This article discusses its current and future applications. PMID- 22083006 TI - Medical leadership: an international perspective. AB - Doctors are increasingly seen as key to embedding health service improvements and there has been much international debate over how best this can be achieved. This article takes an international perspective on medical leadership and leadership development through discussion of case study examples and initiatives from around the world. PMID- 22083007 TI - Learning to make better clinical decisions. AB - To achieve the optimum patient outcome one must be able to choose the most appropriate course of action. How this choice is made may not be actively contemplated, and there may be many unrecognized pitfalls for the unwary. An increased awareness of how we think should increase both the efficiency and success of clinical decision making. PMID- 22083008 TI - Inverted takotsubo cardiomyopathy secondary to adrenaline injection. AB - A young woman presented with severe chest pain and an inverted takotsubo cardiomyopathy following adrenaline injection for treatment of an allergic reaction. To the authors' knowledge, this is the first reported case of inverted takotsubo cardiomyopathy following systemic adrenaline administration. The case strongly suggests a central role of catecholamines in the pathogenesis of takotsubo cardiomyopathy. PMID- 22083009 TI - Vasodepressor syncope and recurrent pharyngeal carcinoma: a form of carotid sinus syndrome? AB - Syncope occurring in the setting of head and neck malignancy may have several possible causes. Local effects of a tumour in the parapharyngeal area may produce a syncopal syndrome similar to carotid sinus hypersensitivity, but with distinctive differentiating features. This article presents a case of profound vasodepressor syncope in a patient with recurrent pharyngeal malignancy, and discusses the mechanisms by which this occurs and the possible therapeutic options. PMID- 22083010 TI - Pulmonary and paradoxical embolism with platypnoea-orthodeoxia. AB - This article outlines the case of a 62-year-old man who presented with a deep vein thrombosis, pulmonary embolus and right middle cerebral artery territory ischaemic stroke in association with a patent foramen ovale with right-to-left shunting. Despite anticoagulation, he was noted to have desaturation and tachypnoea when upright, without other symptoms or cardiovascular compromise, that resolved on lying down. The article describes the syndrome of platypnoea orthodeoxia, characterized by breathlessness, hypoxia and/or cyanosis while in the upright position that improves on lying down, its relationship to this case, and its resolution by closure of the patent foramen ovale. PMID- 22083011 TI - Ileo-ileal intussusception from Crohn's ileitis. AB - Crohn's disease can cause abdominal pain and diarrhoea. A 33-year-old man presented with a 3-month history of recurrent abdominal pain and occasional diarrhoea. PMID- 22083012 TI - Sir Samuel Wilks (1824-1911): brilliant observer who 'rediscovered' Hodgkin's disease. AB - Guy's Hospital and its medical school rejoiced in a remarkable group of physicians in the 19th century. These included Richard Bright, a pioneer in the study of chronic nephritis, Thomas Addison, who described two diseases that bear his name (Addison's disease of the suprarenals and Addison's, or pernicious, anaemia), Thomas Hodgkin, who gave the first clear account of lymphadenoma and Sir William Gull, who documented myxoedema, its relationship to the thyroid and its resemblance to cretinism in children. PMID- 22083013 TI - Dupuytrent's disease and occupation: still a debate? PMID- 22083014 TI - Helping your children save for the future. AB - This autumn sees the launch of junior individual saving accounts, which allow family members and friends to save on behalf a child. This article explains what they are and the other options available to help parents save for their children's future. PMID- 22083016 TI - Supportive therapy with extracorporeal membrane oxygenation for acute respiratory distress syndrome. AB - Acute respiratory distress syndrome is a severe form of respiratory failure characterized by acute onset of significant hypoxaemia (PaO2:FiO2<200mmHg) with diffuse bilateral pulmonary air-space shadowing on chest X-ray, without clinical signs of heart failure (Bernard et al, 1994). It has a heterogeneous aetiology with wide-ranging pulmonary and extra-pulmonary causes. PMID- 22083017 TI - H2 dissociation on individual Pd atoms deposited on Cu(111). AB - We present a Molecular Dynamics (MD) study based on Density Functional Theory (DFT) calculations for H(2) interacting with a Pd-Cu(111) surface alloy for low Pd coverages, Theta(Pd). Our results show, in line with recent experimental data, that single isolated Pd atoms evaporated on Cu(111) significantly increase the reactivity of the otherwise inert pure Cu surface. On top of substitutional Pd atoms in the Pd-Cu(111) surface alloy, the activation energy barrier for H(2) dissociation is smaller than the lowest one found on Cu(111) by a factor of two: 0.25 eV vs. 0.46 eV. Also in agreement with experiments, our DFT-MD calculations show that a large fraction of the dissociating H atoms efficiently spillover from Pd (i.e. the active sites), thanks to their extra kinetic energy due to the ~0.50 eV chemisorption exothermicity. Still, our DFT-MD calculations predict a dissociative sticking probability for low energy H(2) molecules that is much smaller than the estimated value from scanning tunneling microscopy experiments. Thus, further theoretical and experimental investigations are required for a complete understanding of H(2) dissociation on low-Theta(Pd) Pd-Cu(111) surface alloys. PMID- 22083018 TI - Should minimization replace randomization in all clinical trials? PMID- 22083019 TI - Efficient derivation of human cardiac precursors and cardiomyocytes from pluripotent human embryonic stem cells with small molecule induction. AB - To date, the lack of a suitable human cardiac cell source has been the major setback in regenerating the human myocardium, either by cell-based transplantation or by cardiac tissue engineering. Cardiomyocytes become terminally-differentiated soon after birth and lose their ability to proliferate. There is no evidence that stem/progenitor cells derived from other sources, such as the bone marrow or the cord blood, are able to give rise to the contractile heart muscle cells following transplantation into the heart. The need to regenerate or repair the damaged heart muscle has not been met by adult stem cell therapy, either endogenous or via cell delivery. The genetically stable human embryonic stem cells (hESCs) have unlimited expansion ability and unrestricted plasticity, proffering a pluripotent reservoir for in vitro derivation of large supplies of human somatic cells that are restricted to the lineage in need of repair and regeneration. Due to the prevalence of cardiovascular disease worldwide and acute shortage of donor organs, there is intense interest in developing hESC-based therapies as an alternative approach. However, how to channel the wide differentiation potential of pluripotent hESCs efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and clinical translation. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, resulting in inefficient and uncontrollable lineage-commitment that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity (see a schematic in Fig. 1A). In addition, undefined foreign/animal biological supplements and/or feeders that have typically been used for the isolation, expansion, and differentiation of hESCs may make direct use of such cell-specialized grafts in patients problematic. To overcome these obstacles, we have resolved the elements of a defined culture system necessary and sufficient for sustaining the epiblast pluripotence of hESCs, serving as a platform for de novo derivation of clinically-suitable hESCs and effectively directing such hESCs uniformly towards clinically-relevant lineages by small molecules (see a schematic in Fig. 1B). After screening a variety of small molecules and growth factors, we found that such defined conditions rendered nicotinamide (NAM) sufficient to induce the specification of cardiomesoderm direct from pluripotent hESCs that further progressed to cardioblasts that generated human beating cardiomyocytes with high efficiency (Fig. 2). We defined conditions for induction of cardioblasts direct from pluripotent hESCs without an intervening multi-lineage embryoid body stage, enabling well-controlled efficient derivation of a large supply of human cardiac cells across the spectrum of developmental stages for cell-based therapeutics. PMID- 22083021 TI - Venous thromboembolism: Increased embolic risk from combined oral contraceptives. PMID- 22083022 TI - Radiation exposure from diagnostic imaging among patients with gastrointestinal disorders. AB - BACKGROUND & AIMS: There are concerns about levels of radiation exposure among patients who undergo diagnostic imaging for inflammatory bowel disease (IBD), compared with other gastrointestinal (GI) disorders. We quantified imaging studies and estimated the cumulative effective dose (CED) of radiation received by patients with organic and functional GI disorders. We also identified factors and diagnoses associated with high CEDs. METHODS: We analyzed data from 2590 patients who were diagnosed with GI disorders at a tertiary gastroenterology center from January 1999-January 2009 on the basis of International Statistical Classification of Diseases and Health-related Problems, 10th revision and Rome III criteria. High annual CED and high total CED were defined as figures exceeding the 90th percentile for the population. RESULTS: Diagnostic imaging was performed on 57% of the patients (1429 of 2509). High annual CEDs (>9.6 millisieverts/annum) were independently associated with Crohn's disease (odds ratio [OR], 5.3; P < .0001), organic small bowel disease (OR, 2.6; P < .005), and functional disorders of childhood and adolescence (OR, 9.8; P < .005). High total CEDs (>30.8 millisieverts) were independently associated with Crohn's disease (OR, 81.9; P < .0001), ulcerative colitis (OR, 19.0; P < .0001), indeterminate colitis (OR, 7.5; P < .0005), and the following non-IBD diagnoses: organic small bowel disorders (OR, 12.5; P < .0001), organic hepatic disorders (OR, 3.6; P < .01), and functional disorders of childhood and adolescence (OR, 13.8; P = .02). CONCLUSIONS: Higher levels of annual and total diagnostic radiation exposure are associated with IBD and with other organic and functional GI disorders. Evidence based guidelines for image analysis of patients with organic and functional gastrointestinal disorders, especially those that reduce radiation exposure, are needed. PMID- 22083020 TI - Transcatheter aortic valve implantation: current and future approaches. AB - The first human transcatheter aortic valve implantation (TAVI) in 2002, and several subsequent single-center series, showed the feasibility of this new approach for the treatment of patients with severe aortic stenosis who were considered to be at very high or prohibitive surgical risk. More-recent multicenter registries have confirmed the safety and efficacy of this procedure, despite a very-high-risk patient profile. Moreover, the randomized, controlled PARTNER trial has confirmed both the superiority of TAVI over medical treatment in patients not considered to be candidates for standard surgical aortic valve replacement and the noninferiority of TAVI compared with surgical aortic valve replacement in high-risk patients. The hemodynamics of transcatheter valves are usually excellent, although residual paravalvular aortic regurgitation (usually trivial or mild) is frequent. Stroke, major vascular complications, and conduction disturbances leading to permanent pacemaker implantation remain among the most-concerning periprocedural complications of TAVI. Nevertheless, promising preliminary data exist for long-term outcomes following TAVI, 'valve-in-valve' TAVI for surgical prosthesis dysfunction, and for the treatment of lower-risk patients. Improvements in transcatheter valve technology, optimization of procedural and midterm results, and confirmation of long-term durability of transcatheter valve prostheses will determine the expansion of TAVI towards the treatment of a broader spectrum of patients. PMID- 22083023 TI - Multidisciplinary management of hepatocellular carcinoma. AB - Hepatocellular carcinoma is a leading cause of death in patients with cirrhosis. Management algorithms continually are increasing in sophistication and involve application of single and multimodality treatments, including liver transplantation, hepatic resection, ablation, transarterial chemoembolization, radioembolization, and systemic chemotherapy. These treatments have been shown to increase survival times. As many as 75% of patients with limited-stage disease who are given curative therapies survive 5 years, whereas less than 20% of untreated patients survive 1 year. Treatment can be optimized based on the patient's tumor stage, hepatic reserve, and functional status. However, because of the heterogeneity in presentation among patients, a multidisciplinary approach is required to treat hepatocellular carcinoma, involving hepatologists, surgeons, interventional radiologists, and oncologists. We present each specialist's viewpoint on controversies and advances in the management of hepatocellular carcinoma. PMID- 22083024 TI - Efficacy of topical 5-aminosalicylates in preventing relapse of quiescent ulcerative colitis: a meta-analysis. AB - BACKGROUND & AIMS: Topical 5-aminosalicylates (5-ASAs) such as mesalamine are effective in inducing remission in patients with mild to moderately active ulcerative colitis (UC). However, there has been no meta-analysis of their efficacy in preventing relapse of quiescent UC. METHODS: We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials through July 2011 for randomized controlled trials comparing the effects of topical 5-ASAs with placebo in adults with quiescent UC. Dichotomous data were pooled to obtain relative risk (RR) of relapse of disease activity. The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Adverse events data were summarized. RESULTS: The search identified 3061 citations; we analyzed data from seven (555 patients). All trials used mesalamine, but only one included patients with extensive disease. The duration of therapy ranged from 6-24 months. The RR of relapse of disease activity in patients with quiescent UC who were given topical mesalamine, compared with placebo, was 0.60 (95% confidence interval, 0.49-0.73; NNT = 3); there was no significant heterogeneity between studies (I(2) = 21%, P = .27). No significant differences in rates of adverse events rates were detected (RR = 1.01; 95% confidence interval, 0.59-1.72). CONCLUSIONS: On the basis of a meta-analysis of 7 randomized controlled trials, topical mesalamine is effective in preventing relapse of quiescent UC, with no greater number of adverse events than placebo. However, because most studies included only patients with left-sided disease or proctitis, the efficacy of topical mesalamine in preventing relapse in patients with more extensive quiescent UC is not known. PMID- 22083025 TI - Mechanistic insights on one-phase vs. two-phase Brust-Schiffrin method synthesis of Au nanoparticles with dioctyl-diselenides. AB - Metal precursors in the one-phase (1p) and two-phase (2p) Brust-Schiffrin method (BSM) synthesis of Au nanoparticles (NPs) using dioctyl-diselenides were identified. A single dominant type of metal precursor was found in the 1p synthesis as compared to multiple ones in the 2p synthesis, which was proposed as the key reason why the former is better than the latter. PMID- 22083027 TI - Substrate selected polymorphism of epitaxially aligned tetraphenyl-porphyrin thin films. AB - Porphyrin molecules, of interest as versatile materials for organic electronics, are highly prone to formation of significantly different polymorphic phases. To elucidate the determinants for the specific polymorphic phase formed in thin films as well as for the arrangement of the molecules on a given substrate two different anisotropic substrate surfaces have been selected: KCl(100) and the oxygen reconstructed Cu(110) surface. We observe that the crystal structure of the thin films depends on the substrate, whereas the relative molecular orientations in both cases are similar. X-Ray and transmission electron diffraction of 30 nm thick tetraphenyl-porphyrin (H(2)TPP) and platinum tetraphenyl-porphyrin (PtTPP) thin films deposited on KCl(100) surfaces reveals that both kinds of molecules crystallize in a tetragonal polymorph with the (001) lattice planes, i.e. with their macrocycles, parallel to the substrate. Films deposited on the oxygen reconstructed Cu(110)-(2 * 1)O surface exhibit in contrast the triclinic polymorph even though molecules again align nearly parallel to the substrate surface as observed by LEED and X-ray diffraction. On both substrates we identify two driving forces for the epitaxial alignment of porphyrins: (i) molecules aligning with their macrocycles (nearly) parallel to the substrate surface and (ii) the porphyrin molecules forming a commensurate unit cell with the respective substrate. The polymorphic phase meeting both requirements is the most favorable to be formed on a given substrate and due to this structural flexibility in both cases well-ordered, epitaxially aligned porphyrin thin films are achieved. PMID- 22083026 TI - Attention training and the threat bias: an ERP study. AB - Anxiety is characterized by exaggerated attention to threat. Several studies suggest that this threat bias plays a causal role in the development and maintenance of anxiety disorders. Furthermore, although the threat bias can be reduced in anxious individuals and induced in non-anxious individual, the attentional mechanisms underlying these changes remain unclear. To address this issue, 49 non-anxious adults were randomly assigned to either attentional training toward or training away from threat using a modified version of the dot probe task. Behavioral measures of attentional biases were also generated pre- and post-training using the dot probe task. Event-related potentials (ERPs) were generated to threat and non-threat face pairs and probes during pre- and post training assessments. Effects of training on behavioral measures of the threat bias were significant, but only for those participants showing pre-training biases. Attention training also influenced early spatial attention, as measured by post-training P1 amplitudes to cues. Results illustrate the importance of taking pre-training attention biases in non-anxious individuals into account when evaluating the effects of attention training and tracking physiological changes in attention following training. PMID- 22083028 TI - Effect of anemia on hepatotoxicity of HAART in HIV patients in Benin city. AB - BACKGROUND: Hepatotoxicity is a relevant adverse effect of highly active antiretroviral Treatment owing to its frequency, and it can cause interruption of therapy, hepatitis, and death. There is dearth of information on hepatotoxicity arising from highly active antiretroviral therapy (HAART) in anemic patients. Anemia is the most common symptom in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. We studied the effect of anemia on hepatotoxicity in HIV patients who were about to start HAART, attending clinic, or in the medical wards. MATERIALS AND METHODS: This was a prospective study in which patients were recruited consecutively and followed up for 24 weeks. RESULTS: In all, 84 patients were recruited and 42 were enrolled as controls. The mean ages of the cases and controls were 35.2+/-9.9 and 35.5+/-9.0 years, respectively. The age range of the cases was 18-68 years with a median age of 31.5 years, whereas the mean age of the controls was 20-57 years with a median age of 33.5 years. There was no difference (t=0.197, df=124, and P=0.844). There were 61 females (72.6%) and 23 males (27.4%) in the cases, whereas in the controls, there were 34 females (81.0%) and 8 males (19.0%). Among the cases, 30 (35.7%) were anemic, while 54 (64.3%) were not anemic. Six (20%) of the anemic patients had hepatotoxicity, and 9 (16.7%) of the patients with normal packed cell volume had hepatotoxicity. Among the controls, all 42 (100%) patients had normal packed cell volume. Four (9.5%) of the patients had hepatotoxicity. There was no association between hepatotoxicity and anemia (chi(2) =3.243, df=2, P=0.198). CONCLUSION: Anemia did not affect hepatotoxicity of HAART in this study. PMID- 22083029 TI - A general method for evaluating incubation of sucrose craving in rats. AB - For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and relapse to food taking. Food craving conceptualized in this way is akin to drug craving in response to drug-paired cues. A rich literature has been developed around understanding the behavioral and neurobiological determinants of drug craving; we and others have been focusing recently on translating techniques from basic addiction research to better understand addiction-like behaviors related to food. As done in previous studies of drug craving, we examine sucrose craving behavior by utilizing a rat model of relapse. In this model, rats self-administer either drug or food in sessions over several days. In a session, lever responding delivers the reward along with a tone+light stimulus. Craving behavior is then operationally defined as responding in a subsequent session where the reward is not available. Rats will reliably respond for the tone+light stimulus, likely due to its acquired conditioned reinforcing properties. This behavior is sometimes referred to as sucrose seeking or cue reactivity. In the present discussion we will use the term "sucrose craving" to subsume both of these constructs. In the past decade, we have focused on how the length of time following reward self administration influences reward craving. Interestingly, rats increase responding for the reward-paired cue over the course of several weeks of a period of forced abstinence. This "incubation of craving" is observed in rats that have self administered either food or drugs of abuse. This time-dependent increase in craving we have identified in the animal model may have great potential relevance to human drug and food addiction behaviors. Here we present a protocol for assessing incubation of sucrose craving in rats. Variants of the procedure will be indicated where craving is assessed as responding for a discrete sucrose paired cue following extinction of lever pressing within the sucrose self administration context (Extinction without cues) or as responding for sucrose paired cues in a general extinction context (Extinction with cues). PMID- 22083030 TI - The role of atrial natriuretic peptide in modulating cardiac electrophysiology. AB - Since the discovery of atrial natriuretic peptide (ANP) in 1981, significant progress has been made in understanding the mechanism of its release and its role in salt and water balance in the body. It has also become clear that ANP plays a key role in cardiac electrophysiology, modulating the autonomic nervous system and regulating the function of cardiac ion channels. The clinical importance of this role was established when mutations in NPPA, the gene encoding ANP, were identified as a cause of familial atrial fibrillation. This review examines our current understanding of the electrophysiological effects of ANP, and their physiological relationship to clinical studies linking ANP and atrial fibrillation. PMID- 22083031 TI - Device surgery in the anticoagulated patient: the Goldilocks principle. PMID- 22083033 TI - To the editor--ablation of persistent atrial fibrillation. PMID- 22083037 TI - Control of medical comorbidities in individuals with HIV. AB - BACKGROUND: With improved combination antiretroviral therapy-related survival, diabetes and hypertension increasingly contribute to morbidity and mortality among individuals with HIV. However, there is limited data on diabetes and blood pressure control in this population. We examined whether virologic control is associated with control of diabetes and hypertension. METHODS: We examined HIV viral load, hemoglobin A1c (HbA1c), and blood pressure measurements from 70 diabetics and 291 hypertensives in the Johns Hopkins HIV Clinical Cohort, an urban, university-based cohort. All patients were treated for HIV and diabetes or hypertension. HbA1c and HIV-1 RNA were captured electronically from laboratory data, and blood pressure was collected electronically from vital signs taken at clinic visits. We used HIV-1 RNA values within 30 days of the HbA1c measurement or blood pressure measurement. The relationships between HIV-1 RNA and HbA1c and HIV-1 RNA and blood pressure were examined using separate random effects generalized least squares linear regression models. RESULTS: The study sample was predominantly male and black, with a high prevalence of comorbid hepatitis C virus infection and psychiatric illness. In multivariable analysis, each log(10) increase in HIV-1 RNA was associated with higher HbA1c (beta = 0.47 units, P < 0.001) among diabetics and higher mean arterial pressure among hypertensive patients (beta = 1.95 mmHg, P < 0.001). CONCLUSIONS: Suboptimal control of HIV, indicated by detectable viral load, correlates with suboptimal control of diabetes and hypertension, indicated by higher HbA1c and mean arterial pressure. Achieving control of multiple medical comorbidities and HIV simultaneously may require expansion of current adherence interventions focused primarily on antiretroviral therapy. PMID- 22083039 TI - Raman spectrum of supercritical C(18)O2 and re-evaluation of the Fermi resonance. AB - We report the first Raman spectra of fully (18)O-labeled supercritical CO(2) (scCO(2)) and various isotopic mixtures. The experimental results, coupled with ab initio molecular dynamics calculations, demonstrate that the frequencies assigned to the Fermi dyad of the CO(2) molecule transpose upon isotopic labeling of both oxygen atoms. Although the transposition of the Fermi dyad of CO(2) gas due to isotopic substitution has been discussed before, this is the first confirmation of the effect in the Raman spectrum of the supercritical fluid and provides necessary groundwork for future Raman spectroscopy studies of reactions in this important medium. More importantly, the work yields a quantitative assessment of the mixing of states upon labeling that provides the needed clarification concerning the pedigree of the assignments for the dyad of CO(2) under supercritical conditions. PMID- 22083040 TI - Disease prevention: Pain killer--cancer preventer. PMID- 22083038 TI - Efficacy of behavioral interventions to increase condom use and reduce sexually transmitted infections: a meta-analysis, 1991 to 2010. AB - OBJECTIVE: In the absence of an effective HIV vaccine, safer sexual practices are necessary to avert new infections. Therefore, we examined the efficacy of behavioral interventions to increase condom use and reduce sexually transmitted infections (STIs), including HIV. DESIGN: Studies that examined a behavioral intervention focusing on reducing sexual risk, used a randomized controlled trial or a quasi-experimental design with a comparison condition, and provided needed information to calculate effect sizes for condom use and any type of STI, including HIV. METHODS: Studies were retrieved from electronic databases (eg, PubMed, PsycINFO) and reference sections of relevant papers. Forty-two studies with 67 separate interventions (N = 40,665; M age = 26 years; 68% women; 59% Black) were included. Independent raters coded participant characteristics, design and methodological features, and intervention content. Weighted mean effect sizes, using both fixed-effects and random-effects models, were calculated. Potential moderators of intervention efficacy were assessed. RESULTS: Compared with controls, intervention participants increased their condom use [d+ = 0.17, 95% confidence interval (CI) = 0.04, 0.29; k = 67], had fewer incident STIs (d+ = 0.16, 95% CI = 0.04, 0.29; k = 62), including HIV (d+ = 0.46, 95% CI = 0.13, 0.79; k = 13). Sample (eg, ethnicity) and intervention features (eg, skills training) moderated the efficacy of the intervention. CONCLUSIONS: Behavioral interventions reduce sexual risk behavior and avert STIs and HIV. Translation and widespread dissemination of effective behavioral interventions are needed. PMID- 22083041 TI - Screening: get it off your chest. PMID- 22083043 TI - Platinum nanoparticles suppress osteoclastogenesis through scavenging of reactive oxygen species produced in RAW264.7 cells. AB - Recent research has shown that platinum nanoparticles (nano-Pt) efficiently quench reactive oxygen species (ROS) as a reducing catalyst. ROS have been suggested to regulate receptor activator of NF-kappaB ligand (RANKL)-stimulated osteoclast differentiation. In the present study, we examined the direct effects of platinum nano-Pt on RANKL-induced osteoclast differentiation of murine pre osteoclastic RAW 264.7 cells. The effect of the nano-Pt on the number of osteoclasts was measured and their effect on the mRNA expression for osteoclast differentiation was assayed using real-time PCR. Nano-Pt appeared to have a ROS scavenging activity. Nano-Pt decreased the number of osteoclasts (2+ nuclei) and large osteoclasts (8+ nuclei) in a dose-dependent manner without affecting cell viability. In addition, this agent significantly blocked RANKL-induced mRNA expression of osteoclastic differentiation genes such as c-fms, NFATc1, NFATc2, and DC-STAMP as well as that of osteoclast-specific marker genes including MMP-9, Cath-K, CLC7, ATP6i, CTR, and TRAP. Although nano-Pt attenuated expression of the ROS-producing NOX-family oxidases, Nox1 and Nox4, they up-regulated expression of Nox2, the major Nox enzyme in macrophages. These findings suggest that the nano Pt inhibit RANKL-stimulated osteoclast differentiation via their ROS scavenging property. The use of nano-Pt as scavengers of ROS that is generated by RANKL may be a novel and innovative therapy for bone diseases. PMID- 22083042 TI - Targeted therapies: how personal should we go? AB - Despite the development of drugs inhibiting the oncogenic proteins that cancer cells are dependent on, attempts to match targeted therapies to the genetic makeup of individual tumors is proving more difficult than expected. Until now, the paradigm has been a binary correlation between a mutated cancer gene and response to a given therapy. However, recent evidence indicates that different genetic alterations, such as mutations in different codons of a cancer gene, might be related to distinct sensitivity to targeted therapies. An example is the divergent effect that individual EGFR, PIK3CA and KRAS mutations might have on response or resistance to tailored drugs. Furthermore, the idea that the presence of a specific mutation translates into sensitivity or resistance to a particular drug is likely too simplistic, since it does not capture the complexity of the signaling pathways in an individual cancer. Only the overall genetic milieu (alterations in upstream and/or parallel pathways) ultimately determines the response of individual tumors to therapy. We have critically analyzed data supporting the genetic, biological and biochemical differences of individual mutations within a single cancer gene. The role of cancer mutations as predictors of sensitivity and resistance to targeted therapies is discussed, together with the implications for the 'personalized' treatment of cancer patients. PMID- 22083044 TI - Diabetes-induced central cholinergic neuronal loss and cognitive deficit are attenuated by tacrine and a Chinese herbal prescription, kangen-karyu: elucidation in type 2 diabetes db/db mice. AB - We investigated the effect of kangen-karyu (KK), a Chinese herbal prescription, on cognitive deficits and central cholinergic systems of type 2 diabetic db/db mice. Seven-week-old db/db (Y-db/db) mice received daily administration of test drugs during an experimental period of 12 weeks. At 18 weeks of age (O-db/db), the animals underwent the water maze test. Compared with age-matched control strain mice (O-m/m), vehicle-treated O-db/db mice showed impaired learning and memory performance. KK (100 - 200 mg/kg per day) and the reference drug tacrine (THA: 2.5 mg/kg per day) ameliorated the performance of O-db/db mice without affecting their serum glucose level. O-db/db mice had lower levels of brain derived neurotrophic factor (BDNF) mRNA and its protein in the brain than O-m/m mice. Expression levels of central cholinergic marker proteins in the hippocampus and the number of cholinergic cells in the medial septum and basal forebrain were also significantly lower in O-db/db than in O-m/m mice, whereas no significant differences in the expression levels of these factors and the cell number were found between Y-m/m and Y-db/db mice. KK and THA treatment significantly reversed the down-regulated levels of cholinergic markers, choline acetyltransferase positive cell number, and BDNF expression in db/db mice. These findings suggest that KK as well as THA prevents diabetes-induced cognitive deficits by attenuating dysfunction of central cholinergic systems. PMID- 22083045 TI - Altruism in clinical research: coordinators' orientation to their professional roles. AB - OBJECTIVE: Research coordinators have significant responsibilities in clinical trials that often require them to find unique ways to manage their jobs, thus reshaping their professional identities. The purpose of this study was to identify how research coordinators manage role and ethical conflicts within clinical research trials. METHODS: A qualitative study combining observation and 63 semistructured interviews at 25 research organizations was used. RESULTS: Altruism is a recurring theme in how research coordinators define and view their work. CONCLUSION: Altruism is adopted by research coordinators to: (1) Teach patient-subjects the appropriate reasons to participate in clinical research, (2) minimize the conflict between research and care, and (3) contest the undervaluation of coordinating. Altruism is a strategy used to handle the various conflicts they experience in a difficult job, and it has become part of the professional identity of clinical research coordinators. PMID- 22083046 TI - [Implantation of the endo-exo femur prosthesis to improve the mobility of amputees]. AB - OBJECTIVE: Improvement of function following above-knee amputation with an osseointegrated, transcutaneous femoral implant as a hard point for the exo prosthesis, the so-called endo-exo femur prosthesis (EEFP). INDICATIONS: Above knee amputation following trauma, tumor, or infection. CONTRAINDICATIONS: Diabetes, PAOD, psychiatric diseases, use of chemotherapeutic or corticosteroid medication, nonconcluded bone growth, lack of compliance, and florid infection at the time of implantation. SURGICAL TECHNIQUE: Performed as a two-step procedure: Stage 1 (implantation): sharp dissection of the end of the residual bone, adequate access to the intramedullar canal, cortical reaming using curettes and a flexible drill followed by cement-free, press-fit implantation of the endoprosthesis itself, closing of the soft tissue coat of the femur stump to reduce the risk of infection, assurance of primary and secondary stability via the metal spongiosa-like surface of the implant (Spongiosa Metal 2(r)). Stage 2 (exteriorization): 6 weeks postoperatively, opening of the skin at the distal point of the femur stump, the soft tissue between the skin and endoprosthesis is then removed and the double conus and the connecting adapter for the exoprothesis is attached. POSTOPERATIVE MANAGEMENT: Ascending weight bearing depending on bone quality. On average, full weight bearing can be achieved 8-10 weeks after stage 1 surgery. RESULTS: The first endo-exo femur prosthesis (EEFP) was implanted in 1999. Through December 2009, 39 cases were operated in Lubeck, early serosanguinous drainage, soft tissue problems at the stoma, and ascending infections after mobilization of the patients could be minimized by further development of the design of the EEFP. Intramedullary infections were the exception (1 of 39 patients). A total of 4 explantations had to be performed (3 due to infection and 1 due to prosthetic failure). Two of those patients were again provided with an EEFP. Overall, the EEFP improved the gait pattern because of the bone-guided transmission of muscle power, increased osseoperception, and improved economical energy balance. Of the 39 patients, 37 said that they would again undergo operation. PMID- 22083047 TI - Anatomical glenoid reconstruction via a J-bone graft for recurrent posttraumatic anterior shoulder dislocation. AB - OBJECTIVE: To reconstruct the anatomical glenoid shape in cases of osseous glenoid rim defects after recurrent posttraumatic anterior shoulder dislocation to restore stability without severely compromising the range of motion. INDICATIONS: Osseous glenoid defects after recurrent posttraumatic anterior shoulder dislocation. Suitable for primary stabilization as well as for revision surgery in cases previously operated on. CONTRAINDICATIONS: Recurrent anterior shoulder dislocations without glenoid rim defects. Hyperlax shoulders with multidirectional instability. Patients over 60 years of age due to compromised bone quality. Teenage patients due to incomplete apophyseal fusion at the iliac crest. SURGICAL TECHNIQUE: The subscapularis tendon and capsule are split. The humeral head is retracted laterally, and the glenoid defect is prepared and abraded with a rasp. A bicortical iliac crest bone block including crest and outer cortex is harvested and molded in a J-shaped manner. To incorporate the graft, a crevice on the glenoid rim is produced using a chisel. The keel is fitted into the preformed crevice with a spiked impactor. The graft's surface is contoured using a high-speed burr. RESULTS: A total of 47 shoulders were followed up after an average of 90 months (range 25-152 months). The mean Rowe scores were 94.3 for the affected shoulder and 96.8 for the uninjured shoulder. The Constant scores reached 93.5 and 95 points, respectively. Loss of external rotation was 4.4 degrees . In addition, 24 shoulders were followed-up by computed tomography (CT). There were no recurrences, with the exception of one traumatic graft fracture. Of 19 patients with arthropathy at follow-up, 11 already had arthropathy prior to the procedure. PMID- 22083049 TI - Longstanding hydrocele in adult Black Africans: Is preoperative scrotal ultrasound justified? AB - BACKGROUND: Longstanding hydrocele is very common among adult Black Africans. Preoperative scrotal ultrasound is widely used for adult patients presenting with hydrocele, with the main aim to rule out more serious underlying pathologies like malignancy or testicular torsion. This paper analyzes the findings and the necessity of automatic ordering of scrotal ultrasound in cases of longstanding hydrocele in adult Black Africans. MATERIALS AND METHODS: 102 consecutive patients with longstanding scrotal hydrocele were investigated clinically and all patients also had routine preoperative scrotal ultrasound. RESULTS: Overall, none of our patients had any serious underlying pathology associated with their hydrocele. 97% of the patients had simple hydrocele on ultrasound. Hydrocele is more common on the right (P=0.04) and is more bilateral in elderly patients (P=0.0002). CONCLUSIONS: Routine preoperative scrotal ultrasound does not seem to be justified in longstanding hydroceles. This is especially important considering the fact that most hydroceles are benign in origin and nature. PMID- 22083050 TI - Maternal mortality. PMID- 22083052 TI - Magnesium sulfate for fetal neuroprotection. PMID- 22083053 TI - Magnesium sulfate for neuroprotection in patients at risk for early preterm delivery: not yet. PMID- 22083055 TI - Cost-effectiveness of general anesthesia vs spinal anesthesia in fast-track abdominal benign hysterectomy. AB - OBJECTIVE: The study objective was to compare total costs for hospital stay and postoperative recovery for 2 groups of women who underwent fast-track abdominal benign hysterectomy: 1 group under general anesthesia; 1 group under spinal anesthesia. Costs were evaluated in relation to health-related quality of life. STUDY DESIGN: Costs of treatment were analyzed retrospectively with data from a randomized multicenter study at 5 hospitals in Sweden. Of 180 women who were scheduled for benign abdominal hysterectomy, 162 women were assigned randomly for the study: 80 women allocated to general anesthesia and 82 women to spinal anesthesia. RESULTS: Total costs (hospital costs plus cost-reduced productivity costs) were lower for the spinal anesthesia group. Women who had spinal anesthesia had a faster recovery that was measured by health-related quality of life and quality adjusted life-years gained in postoperative month 1. CONCLUSION: The use of spinal anesthesia for fast-track benign abdominal hysterectomy was more cost-effective than general anesthesia. PMID- 22083056 TI - Beyond the numbers: classifying contributory factors and potentially avoidable maternal deaths in New Zealand, 2006-2009. AB - OBJECTIVE: We sought to describe a new classification system for contributory factors in, and potential avoidability of, maternal deaths and to determine the contributory factors and potential avoidability among 4 years of maternal deaths in New Zealand. STUDY DESIGN: A new classification system for reporting contributory factors in all maternal deaths was developed from previous tools and applied to all maternal deaths in New Zealand from 2006 through 2009. RESULTS: There were 49 deaths and the maternal mortality ratio was 19.2/100,000 maternities. Contributory factors were identified in 55% of cases. An expert panel identified 35% of maternal deaths as potentially avoidable. In cases where potential avoidability was determined, there were nearly always 2 or 3 domains where contributory factors were identified. CONCLUSION: Almost one third of maternal deaths in New Zealand can be considered to be potentially avoidable. This methodology has the potential to identify areas for improvement in the quality of maternity care. PMID- 22083057 TI - First-trimester screening in triplets. AB - OBJECTIVE: The purpose of this study was to determine the performance of Down syndrome screening in triplet pregnancy. STUDY DESIGN: Nuchal translucency (NT; n = 794), nasal bone (n = 219), and biochemistry (n = 198) were evaluated in triplet pregnancy. Screening performance was evaluated with the use of delta and Gaussian models. RESULTS: The median multiples of the median values for free beta human chorionic gonadotropin and pregnancy-associated plasma protein A were 2.86 and 3.48, respectively. A significant correlation in delta NT within pregnancy was observed (0.46-0.68). The modeled false-positive rates were 11.7%, 7.4%, and 8.9% with the delta model and 11.9%, 6.6%, and 12.0% with the Gaussian model for NT, NT + nasal bone, and NT + biochemistry. Based on simulation, the detection rate at 12 weeks' gestation was 78%, 93%, and 80% for NT, NT + nasal bone, and NT + biochemistry at a 10% false-positive rate using either the delta or Gaussian models. CONCLUSION: In triplet pregnancy, the addition of nasal bone lowers the false-positive rate of nuchal translucency screening. More data are required on the effectiveness of biochemistry. PMID- 22083058 TI - Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia. AB - OBJECTIVE: We sought to investigate the mechanisms of action by which pravastatin improves vascular reactivity in a mouse model of preeclampsia induced by overexpression of soluble Fms-like tyrosine kinase-1 (sFlt)-1. STUDY DESIGN: Pregnant CD-1 mice were randomly allocated to tail vein injection with adenovirus carrying sFlt-1 or murine immunoglobulin G2 Fc (control), and thereafter to receive pravastatin (5 mg/kg/d) or water. Mice were sacrificed at gestational day 18. Protein expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor receptor-1, and hemeoxygenase-1 were assayed by Western blot in aorta, liver, and kidneys. Serum total cholesterol concentrations were measured. RESULTS: Pravastatin up-regulated eNOS expression in the aorta of sFlt 1 mice by nearly 2-fold (P = .005) to levels similar to control mice. Total cholesterol levels, vascular endothelial growth factor receptor-1, and hemeoxygenase-1 protein expression were similar across groups. CONCLUSION: Pravastatin prevents vascular dysfunction in part by up-regulation of eNOS in the vasculature. Our data support a role for statins in preeclampsia prevention. PMID- 22083059 TI - Comprehensive maternal hemorrhage protocols improve patient safety and reduce utilization of blood products. AB - OBJECTIVE: The purpose of this study was to assess the effectiveness of instituting a comprehensive protocol for the treatment of maternal hemorrhage. STUDY DESIGN: The protocol was separated into 4 stages, designated 0-3, based on the degree of blood loss and the patient response to interventions. Key components included admission risk assessment, measurement of blood loss, early but limited use of uterotonic agents, early presence of obstetrical and anesthesia staff, and transfusion with fixed ratios of blood products. Data were collected retrospectively and prospectively relative to the start of the protocol. RESULTS: We noted a significant shift toward resolution of maternal bleeding at an earlier stage (P < .01), use of fewer blood products (P < .01), and a 64% reduction in the rate of disseminated intravascular coagulation. In addition, there were significant improvements in staff and physician perceptions of patient safety (P < .01). CONCLUSION: Comprehensive maternal hemorrhage treatment protocols improve patient safety and reduce utilization of blood products. PMID- 22083060 TI - Use of alcohol-free antimicrobial mouth rinse is associated with decreased incidence of preterm birth in a high-risk population. AB - OBJECTIVE: We sought to determine if treatment of periodontal disease during pregnancy with an alcohol-free antimicrobial mouth rinse containing cetylpyridinium chloride impacts the incidence of preterm birth (PTB) in a high risk population. STUDY DESIGN: This single-blind clinical trial studied pregnant women (6-20 weeks' gestation) with periodontal disease who refused dental care. Subjects receiving mouth rinse were compared to designated controls who did not receive rinse (1 rinse:2 controls), balanced on prior PTB and smoking. Primary outcome was PTB <35 weeks. RESULTS: In all, 226 women were included in the analysis (71 mouth rinse subjects, 155 controls). Incidence of PTB <35 weeks was lower in the rinse group compared to controls (5.6% and 21.9% respectively, P < .01); relative risk was 0.26 (95% confidence interval, 0.096-0.70). Gestational age and birthweight were significantly higher in the rinse group (P < .01). CONCLUSION: A nonalcohol antimicrobial mouth rinse containing cetylpyridinium chloride was associated with decreased incidence of PTB <35 weeks. PMID- 22083061 TI - Midtrimester dilation and evacuation versus prostaglandin induction: a comparison of composite outcomes. AB - OBJECTIVE: The objective of the study was to determine the optimal procedure for midtrimester uterine evacuation. STUDY DESIGN: This was a retrospective cohort study of women undergoing midtrimester uterine evacuation by prostaglandin induction or dilation and evacuation (D&E). Primary outcome was composite complication, defined as any of the following: infection, need for additional surgery, unexpected admission or readmission, serious maternal morbidity, and/or maternal death. RESULTS: Two hundred twenty patients met inclusion criteria: 94 D&E and 126 induction. D&E was associated with less composite complications (15% vs 28%, P = .02), which persisted in adjusted analysis (adjusted odds ratio, 0.38; 95% confidence interval, 0.15-0.99; P = .05). Women in the induction group had higher rates of retained placenta requiring curettage (22% vs 2%, P = .01), whereas cervical injury was more common in the D&E group (5% vs 0%, P = .01). Median length of stay was significantly shorter in the D&E group (5.7 hours vs 28.4 hours, P < .001). CONCLUSION: Midtrimester D&E is associated with fewer complications than prostaglandin induction. PMID- 22083062 TI - A model patient: Female pelvic anatomy can be viewed in diverse 3-dimensional images with a new interactive tool. PMID- 22083063 TI - Discussion: 'Uterine artery embolization vs surgery' by van der Kooij et al. AB - In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: van der Kooij SM, Bipat S, Hehenkemp WJK, et al. Uterine artery embolization vs surgery in the treatment of symptomatic fibroids: a systematic review and metaanalysis. Am J Obstet Gynecol 2011;205:317.e1-18. PMID- 22083064 TI - Comments on Sheiner et al's "Pregnancy outcome of patients who conceive during or after the first year following bariatric surgery". PMID- 22083066 TI - Management of combined soft tissue and osseous defect of the midfoot with a free osteocutaneous radial forearm flap: a case report. AB - Extensive soft tissue and osseous defects of the foot are difficult to manage and often result in amputation. Most of these wounds are created by trauma, but other causes, such as infection and malignancy, can create similar defects. A variety of wound management options exist for the treatment of these challenging wounds, including negative pressure wound therapy, autogenous skin grafting, and the use of skin substitutes, as well as internal and external fixation methods. In the present report, we describe the use of a free osteocutaneous radial forearm flap to manage a 10-cm * 5-cm dorsal soft tissue defect and a 2.5-cm second metatarsal diaphyseal defect in an adult male. PMID- 22083067 TI - Function after total calcanectomy for malignant tumor in a child: is complex reconstruction necessary? AB - Complex reconstruction after calcaneal excision for aggressive or malignant tumors has been advocated. In this report we describe a 7-year-old child who underwent chemotherapy followed by total calcanectomy for a primitive neuroectodermal tumor of the calcaneum. The near-normal function achieved after the operation leads us to believe that complex reconstruction after calcaneal excision is not warranted in every pediatric case. This report also highlights the benefits of the Cincinnati incision for calcanectomy, and describes the gait abnormalities after the operation. To the best of our knowledge, a description of the gait abnormality observed after calcanectomy for tumor resection in a pediatric patient has not been reported up to now. PMID- 22083069 TI - Using cluster heat maps to investigate relationships between body composition and laboratory measurements in HIV-infected and HIV-uninfected children and young adults. AB - Cluster heat maps were used to investigate relationships between body composition, lipid levels, and glucose metabolism in HIV-infected and HIV uninfected children and young adults using data from a cross-sectional study. Three distinct clusters of participants were identified. One group had lower body fat and higher lipid measures and was mostly HIV infected. The other 2 groups were a mix of HIV-infected and HIV-uninfected participants. Of these, 1 cluster had more participants with higher body fat and insulin resistance, which are risk factors for future cardiovascular disease, and the other had relatively normal measurements on all outcomes. PMID- 22083068 TI - CCR5 expression is elevated on endocervical CD4+ T cells in healthy postmenopausal women. AB - BACKGROUND: New HIV-1 infections are increasing in older American women largely through heterosexual transmission. Activated CD4+ T cells and CCR5 expression are linked to HIV-1 susceptibility, but whether these parameters are altered in the cervix of older women is unknown. METHODS: Whole blood and in some instances endocervical brush samples were collected from healthy premenopausal (n = 22) and postmenopausal women (n = 24). Percentages of HLA-DR(DR)+CD38(38)+CD4+ T cells and HIV-1 chemokine coreceptor expression were determined by flow cytometry. RESULTS: Percentages of DR+38+CD4+ T cells were 6 times greater in cervix (median: 6.4%) than blood (median: 1.1%; P < 0.001) but did not differ within each compartment between premenopausal and postmenopausal women (P = 0.2). Postmenopausal women had greater percentages of CCR5+CD4+ and CCR5+DR+38+CD4+ T cells compared with premenopausal women in cervix (median: 70% vs. 42%, P = 0.005; and 80% vs. 57%; P = 0.05, respectively) and blood (medians: 22% vs. 13%, and 76% vs. 62%, respectively; P < 0.001). Postmenopausal women had more CCR5 molecules on cervical DR+38+CD4+ T cells (median: 3176) than premenopausal women (median: 1776; P = 0.02). Age and percent CCR5+CD4+ and CCR5+DR+38+CD4+ cells were linearly related in cervix (r(2) = 0.47, P < 0.001 and r(2) = 0.25, P = 0.01, respectively) and blood (r(2) = 0.20, P = 0.001 and r(2) = 0.31, P < 0.001; respectively), but confounding of age with menopause could not be excluded. Cervical CXCR4 expression did not differ substantially between premenopausal and postmenopausal women. CONCLUSIONS: Elevated cervical CCR5 expression in postmenopausal women may increase their risk for HIV-1 acquisition. Studies are needed to confirm whether elevated CCR5 expression confers increased HIV-1 susceptibility in postmenopausal women, and if it is related to hormonal or nonhormonal effects of aging. PMID- 22083070 TI - Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe. AB - BACKGROUND: Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF over calendar time have not been fully characterised in recent years. METHODS: Calendar time trends in the incidence and prevalence of TCVF from 2000 to 2009 were assessed in patients who started ART from January 1, 1998, and were followed within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). RESULTS: Of 91,764 patients followed for a median (interquartile range) of 4.1 (2.0-7.1) years, 2722 (3.0%) developed TCVF. The incidence of TCVF increased from 3.9 per 1000 person-years of follow-up [95% confidence interval (CI): 3.7 to 4.1] in 2000 to 8.8 per 1000 person-years of follow-up (95% CI: 8.5 to 9.0) in 2005, but then declined to 5.8 per 1000 person-years of follow-up (95% CI: 5.6 to 6.1) by 2009. The prevalence of TCVF was 0.3% (95% CI: 0.27% to 0.42%) at December 31, 2000, and then increased to 2.4% (95% CI: 2.24% to 2.50%) by the end of 2005. However, since 2005, TCVF prevalence seems to have stabilized and has remained below 3%. CONCLUSIONS: The prevalence of TCVF in people who started ART after 1998 has stabilized since around 2005, which most likely results from the decline in incidence of TCVF from this date. The introduction of improved regimens and better overall HIV care is likely to have contributed to these trends. Despite this progress, calendar trends should continue to be monitored in the long term. PMID- 22083072 TI - Associations of sexual identity or same-sex behaviors with history of childhood sexual abuse and HIV/STI risk in the United States. AB - OBJECTIVE: To measure associations of childhood sexual abuse (CSA) with sexual orientation, behaviors, and attractions and HIV/sexually transmitted infection (STI) incidence in a nationally representative sample of men and women. METHODS: Data from the 2004-2005 Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were analyzed, including frequencies of CSA and HIV/STI incidence for 5 subgroups defined by sexual orientation based on identity and behaviors and attraction to the same sex or opposite sex. RESULTS: Overall, 14.9% of women and 5.2% of men reported CSA. Among women, bisexuals, lesbians, and heterosexuals with same-sex partners had 5.3 times, 3.4 times, and 2.9 times the odds, respectively, for CSA occurring sometimes/more frequently (vs. never) compared with heterosexuals not having same-sex partners or attractions. Among men, bisexuals, gay men, and heterosexuals with same-sex partners had 12.8 times, 9.5 times, and 7.9 times the odds, respectively, for CSA. Men and women sometimes or frequently abused had significant increases in odds for HIV/STI incidence compared with those not abused. Among women, sexual minorities had 3.8 times the odds and heterosexuals had 2.8 times the odds, whereas among men, sexual minorities had 4.2 times odds and heterosexuals had 1.5 times odds. CONCLUSIONS: Extraordinarily high rates of CSA were observed for sexual minorities, and sexual minorities were more likely to have incident HIV or STIs, in this U.S. population survey. Identifying the impact of CSA among heterosexuals and sexual minorities in the US is a crucial first step in examining the sequelae of CSA, including the potential mediators of mental health and substance abuse disorders in the relationship between CSA and sexual risk taking. PMID- 22083071 TI - Efavirenz pharmacokinetics during the third trimester of pregnancy and postpartum. AB - BACKGROUND: The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg EFV once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6-12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile EFV area under the curve (AUC) in nonpregnant historical controls (40.0 mcg.hr(-1).mL(-1)) and a trough concentration of 1 mcg/mL. RESULTS: Twenty-five women were enrolled during the third trimester: median (range) age was 29.3 (18.9-42.9) years, weight 69.0 (40-130) kg, and gestational age 32.9 (30.1-38.7) weeks. Median (range) EFV AUC(0-24), C(max), and C(24 hours) were 55.4 mcg.hr(-1).mL(-1) (13.5-220.3), 5.4 mcg/mL (1.9-12.2), and 1.6 mcg/mL (0.23-8.13), respectively. EFV AUC and C(max) did not differ during pregnancy and postpartum but C(24 hours) was lower during the third trimester (1.6 vs. 2.1 mcg/mL, P = 0.01). During the third trimester, 5 of 25 (20%) women had an EFV AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. EFV cord blood/maternal concentration ratio was 0.49 (0.37-0.74). All women had a HIV-1 RNA viral load less than 400 copies per milliliter at delivery and 19 (76%) had a viral load below 50 copies per milliliter. One child was perinatally HIV infected. Three women were exposed to EFV throughout the first 6 weeks of pregnancy. EFV was well tolerated, and among the 25 infants, no congenital anomalies or newborn complications were reported. CONCLUSIONS: Changes in EFV pharmacokinetics during pregnancy compared with postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy. PMID- 22083074 TI - Suicidal single gunshot injury to the head: differences in site of entrance wound and direction of the bullet path between right- and left-handed--an autopsy study. AB - The aim of this study was to determine the differences in the anatomical site of a gunshot entrance wound and the direction of the bullet path between right- and left-handed subjects who committed a suicide by a single gunshot injury to the head. The retrospective autopsy study was performed for a 10-year period, and it included selected cases of single suicidal gunshot head injury, committed by handguns. We considered only contact or near-contact wounds. The sample included 479 deceased, with average age 47.1 +/- 19.1 years (range, 12-89 years): 432 males and 47 females, with 317 right-handed, 25 left-handed, and 137 subjects with unknown dominant hand. In our observed sample, most cases involved the right temple as the site of entrance gunshot wound (about 67%), followed by the mouth (16%), forehead (7%), left temple (6%), submental (2%), and parietal region (1%). The left temple, right temple, and forehead were the sites of the gunshot entrance wounds, which were the best predictors of the handedness of the deceased (Spearman rho = 0.149, P = 0.006). Our study showed that the direction of the bullet intracranial path in cases of suicide was even a more potent predictor of the handedness of the deceased (Spearman rho = 0.263, P = 0.000; Wald = 149.503, P = 0.000). PMID- 22083075 TI - The increase in the user rate of child seats is clearly an important factor in the decreases in the rates of death and serious injury. PMID- 22083073 TI - No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy. AB - BACKGROUND: Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV 1 replication. METHODS: We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation. RESULTS: Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV 1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV 1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation. CONCLUSIONS: In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection. PMID- 22083076 TI - Accidental hanging: a novel mobile suspension apparatus partially hidden inside the clothes. AB - Accidental hanging is uncommon. An immobile/fixed and exposed suspension apparatus is seen in almost all cases of hanging. A 50-year-old man, who was drunk, was trying to steal an iron rod by hiding it under his clothing. To secure hiding, he attached it to his body by a loose ligature around the neck, the waist belt of the sarong, and another band around the waist and by his underwear. Sometime later, because of ethanol intoxication, he fell asleep in the sitting position. While he was sitting on the floor, the iron rod was lifted up accidentally, and its upper end was wedged against the wall behind the victim, and the lower end was fixed against the floor. When he fell asleep, the weight of the tilted head acted as the constricting force compressing the neck by the ligature that was used to attach the iron rod to the neck. The cause of death was concluded as hanging in a man with ethanol intoxication. This case highlights a novel mobile suspension apparatus partially hidden inside the clothes, in a case of accidental hanging. A similar case has not been reported in the forensic literature. PMID- 22083077 TI - Radiographic examination using an X-ray tunnel (Passagix) before a forensic autopsy. PMID- 22083078 TI - Unusual death by rubber bullet: should these guns be reclassified as lethal weapons? PMID- 22083079 TI - Does hypernatremia cause subdural hematoma in children?: two case reports and a meta-analysis of the literature. AB - Hypernatremia has been causally linked with subdural hematoma (SDH), but more recently this has been called into question. Conversely, there is a well established link between SDH and injury. We wish to examine the evidence base that hypernatremia in infants and young children causes SDH.We present 2 cases of children with severe hypernatremia whose intracranial contents were assessed by imaging in the first case and postmortem examination in the second. Neither demonstrated SDH. The first case was important as the hypernatremia was iatrogenic occurring in a controlled hospital environment.We also searched the literature from 1950 to 2007, collecting data on all reported cases of hypernatremia in children younger than 7 years whose intracranial contents were examined by imaging, surgery, and/or postmortem examination. Of 124 cases reported in 31 articles, 112 cases developed hypernatremia in the community, and 12 in the hospital. Subdural hematoma was demonstrated in 7 cases, all of which had developed hypernatremia in the community under circumstances that would make it difficult to exclude nonaccidental injury. None of the 12 cases that developed hypernatremia in a controlled hospital environment had SDH.The evidence base supporting the hypothesis that hypernatremia causes SDH is poor, depending on isolated reports with uncertain histories. PMID- 22083080 TI - Fusarium verticillioides fungemia in a liver transplantation patient: successful treatment with voriconazole. AB - Fusarium is an opportunistic fungal pathogen which is emerging as a significant cause of morbidity and mortality in immunocompromised hosts. We present a rare case of F. verticillioides fungemia that occurred in a patient who underwent a second orthotopic liver transplantation for chronic rejection and completely responded to treatment with voriconazole. PMID- 22083081 TI - Tuberculosis patients are characterized by a low-IFN-gamma/high-TNF-alpha response to methylated HBHA produced in M. smegmatis. AB - Whole blood from Mycobacterium tuberculosis-infected subjects was stimulated with heparin-binding hemagglutinin (HBHA). Tuberculosis (TB) patients showed an HBHA specific T-cell response characterized by low-IFN-gamma/high-TNF-alpha secretion, while asymptomatic subjects with latent infection (LTBI) and TB patients under therapy showed a pattern with high IFN-gamma/low TNF-alpha. These results underscore the usefulness of HBHA in helping to distinguish LTBI subjects versus TB patients. PMID- 22083082 TI - Pelvic abscess caused by New Delhi metallo-beta-lactamase-1-producing Klebsiella oxytoca in Taiwan in a patient who underwent renal transplantation in China. PMID- 22083083 TI - The binding of curcumin to various types of canine amyloid proteins. AB - Curcumin is a constituent phenol compound of turmeric, and has been used as a dietary spice and Indian medicine. Curcumin has been reported to inhibit the formation of amyloid beta fibrils and aggregation. In this study, the binding activity of curcumin to various types of canine amyloid was examined. Tissue samples used were lesions of AA, AL, amyloid of canine amyloid-producing odontogenic tumor (Aapot), and senile cardiovascular amyloid (ScA). Curcumin stained all types of amyloid. The binding of curcumin to AA, ScA, and AL was lost by the KMnO(4) treatment, but Aapot maintained the binding. These findings indicate that curcumin binds several types of amyloid, while the binding sites of amyloid molecules might be different from that of Congo red. PMID- 22083084 TI - Alternative BSE risk assessment methodology for beef and beef offal imported into Japan. AB - The Food Safety Commission (FSC) of Japan, established in July 2003, has its own initiative to conduct risk assessments on food stuffs known as "self-tasking assessment". Within this framework, the FSC decided to conduct a risk assessment of beef and beef offal imported into Japan from countries with no previous BSE reports; thus, a methodology was formed to suit to this purpose. This methodology was partly based on the previous assessments of Japanese domestic beef and beef imported from U.S.A./Canada, but some modifications were made. Other organizations' assessment methods, such as those used for BSE status assessment in live cattle by the OIE and EFSA's GBR, were also consulted. In this review, the authors introduce this alternative methodology, which reflects (1) the risk of live cattle in the assessed country including temporal risks of BSE invasion and domestic propagation, with the assessment results verified by surveillance data, and (2) the risk of beef and beef offal consisting of cumulative BSE risk by types of slaughtering and meat production processes implemented and the status of mechanically recovered meat production. Other possible influencing factors such as atypical BSE cases were also reviewed. The key characteristic of the current assessment is a combination of the time-sequential risk level of live cattle and qualitative risk level of meat production at present in an assessed country. PMID- 22083085 TI - Norlittorine and norhyoscyamine identified as products of littorine and hyoscyamine metabolism by (13)C-labeling in Datura innoxia hairy roots. AB - The presence of two compounds, norlittorine and norhyoscyamine, has been reported in leaves and roots of Datura innoxia; however their metabolic origin in the tropane alkaloid pathway has remained unknown. Precise knowledge of this pathway is a necessary pre-requisite to optimize the production of hyoscyamine and scopolamine in D. innoxia hairy root cultures. The exact structure of norlittorine and norhyoscyamine was confirmed by LC-MS/MS and NMR analyses. Isotopic labeling experiments, using [1-(13)C]-phenylalanine, [1'-(13)C] littorine and [1'-(13)C]-hyoscyamine, combined with elicitor treatments, using methyl jasmonate, coronalon and 1-aminocyclopropane-1-carboxylic acid, were used to investigate the metabolic origin of the N-demethylated tropane alkaloids. The results suggest that norlittorine and norhyoscyamine are induced under stress conditions by conversion of littorine and hyoscyamine. We propose the N demethylation of tropane alkaloids as a mechanism to detoxify cells in overproducing conditions. PMID- 22083086 TI - Pharmacotherapy: vandetanib-a new therapeutic option in advanced medullary thyroid cancer. PMID- 22083087 TI - Obesity: influenza immunity impaired in obesity. PMID- 22083088 TI - Gastrointestinal hormones: uroguanylin-a new gut-derived weapon against obesity? AB - A recent report has identified uroguanylin as an endocrine signal that exerts a physiological role in energy homeostasis, adding another factor to the gut-brain axis. From a clinical point of view, several observations highlight the uroguanylin-guanylyl cyclase C pathway as a potential therapeutic target for the development of antiobesity drugs. PMID- 22083090 TI - Understanding the regioselectivity in Scholl reactions for the synthesis of oligoarenes. AB - A short reaction sequence leads to oligoarene derivatives utilising a regioselective Scholl reaction for the unprecedented cyclisation to the mono functionalised oligoarene under methanol elimination. Quantum-chemical investigations reveal the reason for the remarkably high regioselectivity. PMID- 22083089 TI - The multifactorial role of leptin in driving the breast cancer microenvironment. AB - Adipose-tissue-derived signaling molecules, including the adipokines, are emerging as key candidate molecules that link obesity with cancer. Peritumoral, stromal, adipose tissue and secreted adipokines, particularly leptin, have important roles in breast cancer biology. For example, leptin signaling contributes to the metabolic features associated with breast cancer malignancy, such as switching the cells' energy balance from mitochondrial beta-oxidation to the aerobic glycolytic pathway. Leptin also shapes the tumor microenvironment, mainly through its ability to potentiate both migration of endothelial cells and angiogenesis, and to sustain the recruitment of macrophages and monocytes, which in turn secrete vascular endothelial growth factor and proinflammatory cytokines. This article presents an overview of current knowledge on the involvement of leptin in the pathogenesis and progression of breast cancer, highlighted by human, in vitro and animal studies. Data are presented on the functional crosstalk between leptin and estrogen signaling, which further contributes to promotion of breast carcinogenesis. Finally, future perspectives and clinical applications in which leptin and the leptin receptor are considered as potential therapeutic targets for breast cancer are reviewed. PMID- 22083091 TI - Ab initio and empirical defect modeling of LaMnO(3+/-delta) for solid oxide fuel cell cathodes. AB - Sr doped LaMnO(3) is a perovskite widely used for solid oxide fuel cell (SOFC) cathodes. Therefore, there is significant interest in its defect chemistry. However, due to coupling of defect reactions and inadequate constraints of the defect reaction equilibrium constants obtained from thermogravimetry analysis, large discrepancies (up to 4 eV) exist in the literature for defect energetics for Sr doped LaMnO(3). In this work we demonstrate how ab initio energetics and empirical modelling can be combined to develop a defect model for LaMnO(3). Defect formation enthalpies, including concentration dependence due to defect interactions, are extracted from ab initio energies calculated at various defect concentrations. Defect formation entropies for the defect reactions in LaMnO(3) involving O(2-)(solid) <-> 1/2O(2)(gas) + 2e(-) are shown to be accessible through combining the gas phase thermodynamics and simple models for the solid phase vibrational contributions. This simple treatment introduces a useful constraint on fitting defect formation entropies. The predicted defect concentrations from the model show good agreement with experimental oxygen nonstoichiometry vs. P(O(2)) for a wide range of temperatures (T = 873-1473 K), suggesting the effectiveness of the ab initio defect energetics in describing the defect chemistry of LaMnO(3). Further incorporating a temperature dependent charge disproportionation energy within 0.0-0.2 eV, the model is capable of describing both defect chemistry and oxygen tracer diffusivity of LaMnO(3). The model suggests an important role for defect interactions which are typically excluded from LaMnO(3) defect models, and sensitivity of the oxygen defect concentration to the charge disproportionation energy in the high P(O(2)) region. Similar approaches to those used here can be used to model the defect chemistry for other complex oxides. PMID- 22083092 TI - Low abdominal contribution to breathing as daytime predictor of nocturnal desaturation in adolescents and young adults with Duchenne Muscular Dystrophy. AB - In the respiratory management of DMD patients it is still under debate what parameter should indicate the correct timing for institution of nocturnal non invasive ventilation (NIV), in addition to forced vital capacity, which is generally considered as a prognostic marker of disease progression. The aim of this study was to determine if volume variations of rib cage and abdominal compartments measured by Opto-Electronic Plethysmography can be helpful to distinguish between those patients who are in the early stages of nocturnal oxygen desaturation development and those who do not yet. Pulmonary function, abdominal contribution to tidal volume and to inspiratory capacity (%Abd IC) and a set of breathing pattern indexes were assessed in 40 DMD patients older than 14 years and not yet under nocturnal NIV. ROC analysis revealed that among all the considered parameters, %Abd IC in supine position was the best discriminator between DeSat (at least 10% of the night time with SpO(2) < 95%) and NonDeSat patients, providing an area under the curve with 95%CI equal to 0.752. In conclusion, in adolescents and adults DMD patients who present either no sign or only mild nocturnal oxygen desaturation, a reduced abdominal contribution to inspiratory capacity is a marker of the onset of diaphragm weakness and should be considered to identify the correct timing for the institution of nocturnal NIV. PMID- 22083093 TI - Extracranial carotid-vertebral bypass for endovascular access to complex posterior circulation aneurysms: a novel management approach. AB - BACKGROUND: Endovascular embolization is a desirable treatment option for complex posterior circulation aneurysms, particularly recurrent aneurysms or those in difficult-to-access surgical locations. However, endovascular access is occasionally prohibited by proximal vertebral artery (VA) occlusion or vessel tortuosity. One strategy in such instances involves creation of an extracranial bypass conduit to the distal VA. OBJECTIVE: To describe a novel strategy to allow for endovascular treatment of aneurysms at high risk for direct surgery. METHODS: Three cases of carotid-VA bypass performed to provide endovascular access to posterior circulation aneurysms were identified. The clinical indications, radiographic characteristics, operative technique, and outcomes were reviewed. RESULTS: Indications for bypass were previously clipped recurrent basilar tip aneurysm, previously coiled midbasilar aneurysm with compaction requiring stent placement, and distal intracranial VA aneurysm with iatrogenic vertebral dissection/occlusion after initial coil attempt. In all cases, routine endovascular access for primary or stent-assisted coiling was prohibited by VA tortuosity. Bypass with the use of interposition saphenous vein grafts was successfully performed to the C1-C2 region of the V2 segment without complications. The bypass was followed by successful endovascular treatment in all cases 2 to 6 weeks after surgery. In 1 patient, 2 recurrent treatments through the graft were subsequently performed for coil compaction. CONCLUSION: Extracranial carotid-VA bypass can be a valuable tool in the management of complex posterior circulation aneurysms. It is a safe and efficacious technique providing a conduit for repeated access to the posterior circulation in patients with otherwise prohibitive vertebral anatomy. PMID- 22083094 TI - Interactions between gaze-evoked blinks and gaze shifts in monkeys. AB - Rapid eyelid closure, or a blink, often accompanies head-restrained and head unrestrained gaze shifts. This study examines the interactions between such gaze evoked blinks and gaze shifts in monkeys. Blink probability increases with gaze amplitude and at a faster rate for head-unrestrained movements. Across animals, blink likelihood is inversely correlated with the average gaze velocity of large amplitude control movements. Gaze-evoked blinks induce robust perturbations in eye velocity. Peak and average velocities are reduced, duration is increased, but accuracy is preserved. The temporal features of the perturbation depend on factors such as the time of blink relative to gaze onset, inherent velocity kinematics of control movements, and perhaps initial eye-in-head position. Although variable across animals, the initial effect is a reduction in eye velocity, followed by a reacceleration that yields two or more peaks in its waveform. Interestingly, head velocity is not attenuated; instead, it peaks slightly later and with a larger magnitude. Gaze latency is slightly reduced on trials with gaze-evoked blinks, although the effect was more variable during head unrestrained movements; no reduction in head latency is observed. Preliminary data also demonstrate a similar perturbation of gaze-evoked blinks during vertical saccades. The results are compared with previously reported effects of reflexive blinks (evoked by air-puff delivered to one eye or supraorbital nerve stimulation) and discussed in terms of effects of blinks on saccadic suppression, neural correlates of the altered eye velocity signals, and implications on the hypothesis that the attenuation in eye velocity is produced by a head movement command. PMID- 22083095 TI - Pathological features of salivary gland cysts in a Shiba dog with GM1 gangliosidosis: a possible misdiagnosis as malignancy. AB - Salivary gland cysts are often concurrent with GM1 gangliosidosis in Shiba dogs. Although the etiology is unknown, these cysts may be misdiagnosed as malignant due to the accumulation of foamy cells. The present study investigated the cytological, histopathological, immunohistochemical and electron microscopic characteristics of salivary gland cysts in a Shiba dog affected with GM1 gangliosidosis. The salivary gland masses were surgically enucleated and examined clinicopathologically and pathologically in a 7-month-old Shiba dog with GM1 gangliosidosis. Many large cells with rich cytoplasm including vacuoles of various sizes, i.e., foamy cells, were observed in stamp smears from the cut surface of the masses and histopathologically in major parts of the cyst wall. Some of these foamy cells presented features similar to a spider-web appearance. The foamy cells were confirmed to have originated from macrophages based on marked immunohistochemical expression of vimentin, HLA-DR, lysozyme and Iba1. An ultrastructural study demonstrated electron-dense vesicular structures in the vacuolated cells. Therefore, the masses were diagnosed pathologically as benign salivary gland cysts with accumulation of foamy cells. In conclusion, the histopathological features of the salivary gland cysts in this Shiba dog were similar to those of lipoma and/or liposarcoma. In such cases, immunohistochemical and ultrastructural examinations were useful in the differential diagnosis. Practitioners, clinical pathologists and pathologists should take GM1 gangliosidosis into consideration when they encounter salivary gland cysts in Shiba dogs. PMID- 22083096 TI - Sonographic detection of small amounts of free peritoneal gas in beagle dogs. AB - The detection of small amounts of free peritoneal gas in the canine patient can pose a diagnostic dilemma. The objective of this study was to determine how much of this free gas could be detected ultrasonographically. Ultrasound examinations were carried out after increments (0.1 ml) of air were intraperitoneally injected. Via ultrasonography, 0.4 ml of free gas can be reliably detected. The authors concluded that ultrasonography is a very sensitive modality for the detection of small amounts of peritoneal free gas (above 0.4 ml). PMID- 22083097 TI - Do we need meshes in pelvic floor reconstruction? AB - OBJECTIVES: Transvaginally placed mesh in pelvic reconstructive surgery for women with pelvic organ prolapse has gained popularity because of excellent anatomical outcomes, but postoperative mesh-related complications have lead to a number of cautious reviews and warnings. This review focuses on functional outcomes after synthetic transvaginal mesh placement. METHODS: MEDLINE database was searched from 2010 to August 2011 for original articles on transvaginal mesh surgery for pelvic organ prolapse not included in recent reviews. The following search terms were used: pelvic organ prolapse, genital prolapse, cystocele, rectocele and mesh, synthetic graft, and repair. Studies were assessed and appropriate data extracted and tabularized. Studies were excluded if the follow-up time was less than 12 months and if studies did not contain original data or data on subjective outcome. RESULTS: Eleven studies irregularly reported functional outcomes. After trocar-guided transobturator vaginal mesh surgery, symptomatic recurrence of pelvic organ prolapse was reported between 7 and 33%. If analyzed cumulatively, 76 of 370 patients (21%) complained of prolapse symptoms postoperatively. De novo stress urinary incontinence occurred in 12-17% and persisted in up to 68% after trocar-guided mesh surgery. De novo dyspareunia was present between 2 and 15%, worsened or de novo dyspareunia between 25 and 44%. Deteriorating coital incontinence was described in 6 of 16 women after anterior Prolift in one trial. CONCLUSIONS: When counseling women for pelvic reconstructive surgery, we should provide them with evidence-based information on functional outcomes and subsequently take the patient's concerns and preferences into account. Pelvic floor symptoms were scarcely reported in reviewed trials, but demonstrated a worse scenario than anatomical outcomes. PMID- 22083098 TI - 18F-DOPA PET/CT biodistribution consideration in 107 consecutive patients with neuroendocrine tumours. AB - OBJECTIVE: L-6-fluoro 3,4-dihydroxyphenylalanine (18F-DOPA), an amino acid-based radiopharmaceutical, is increasingly being used in the detection and management of neuroendocrine tumours. Knowledge of the normal biodistribution of this radiopharmaceutical is essential for the proper interpretation of such studies, but the literature available is scanty due to the rarity of these tumours. The aim of this study is to evaluate the biodistribution pattern and normal variants of 18F-DOPA in a cohort of patients with neuroendocrine tumours using semiquantitative analysis (maximum standardized uptake value). METHODS: We analysed 107 consecutive 18F-DOPA PET/CT studies of patients referred with medullary carcinoma of the thyroid (43), phaeochromocytoma including cases of Von Hippel Lindau syndrome and multiple endocrine neoplasia type IIA cases (34), paraganglioma (14) and other neuroendocrine tumours (16). The study population were divided into two groups: those with negative 18F-DOPA PET/CT scans (32) and those with positive scans (75). The biodistribution of 18F-DOPA in each group was measured and compared between the two groups. RESULTS: The physiological biodistribution in the basal ganglia and liver parenchyma showed no variability between the two groups. Conversely, uptake in the pancreas (particularly the uncinate process) and adrenals showed considerable variability between the groups. However, these differences were found not to be significant on statistical analysis. CONCLUSION: The data presented may provide useful information in understanding the physiologic biodistribution of DOPA and its variants, for the purpose of improving the interpretation of 18F-DOPA PET/CT. PMID- 22083099 TI - [Complications of peripheral regional anesthesia]. AB - Peripheral regional anesthesia is a commonly used and safe procedure and eneral complications or side effects are generally rare. Nerve damage has an incidence <0.1% depending on the definition and the prognosis is good. To avoid bleeding complications the national standards of block performance under antithrombotic therapy should be respected. Intoxication is mainly the result of accidental intravenous administration and is difficult to treat but higher doses of intravenous lipid emulsions can improve the outcome. Potential infectious complications can occur mainly as a result of catheter techniques and require a strict aseptic approach. Further rare complications are allergies, dislocation of catheters and knotting or loops in catheters. Besides the general complications, there are some specific complications depending on the puncture site, such as pneumothorax or renal puncture. PMID- 22083100 TI - [Future-oriented design of ambulatory surgery. Organizational aspects and medical options]. AB - Ambulatory surgery continues to grow and is slowly becoming routine in the majority of cases. Although the development of ambulatory surgery in Germany appears to be somewhat delayed, this is actually a chance to learn from worldwide experiences and avoid the mistakes others made earlier. This article investigates current trends and developments in day case surgery and discusses the extended role and influence of the anesthetist in the perioperative setting. PMID- 22083102 TI - A comparison of two-electron chemistry performed by the manganese and iron heterodimer and homodimers. AB - Two-electron chemistry with an iron dimer, a manganese dimer, and a manganese iron dimer as a catalyst has been modeled using B3LYP* hybrid density functional theory. The recently discovered MnFe proteins form (at least) two functionally distinct groups, performing radical generation (class Ic ribonucleotide reductase subunit II) and substrate oxidations (subunit II-like ligand-binding oxidases, R2lox), respectively. Proteins from the latter group appear to be functionally similar to the diiron carboxylate proteins that perform two-electron oxidations of substrates, such as methane monooxygenase. To qualitatively determine the potential role of a MnFe center in R2lox, methane hydroxylation with the MnFe heterodimer and with the FeFe and MnMn homodimers is studied. The redox potential of the active state of the Mn(IV)Fe(IV) heterodimer is about 7 kcal mol(-1) lower than that of the active state of the Fe(IV)Fe(IV) homodimer, leading to a high barrier for the rate-limiting hydrogen abstraction with the MnFe site. If the entropy loss is not included, the barriers are lower, and the MnFe heterodimer can therefore have a role in R2lox as an oxidase for larger substrates exergonically bound to the protein. A MnMn center has a high barrier both with and without entropy loss. The higher stability of Fe(IV) in the presence of Mn(IV) in the other site compared with a second Fe(IV) suggests an explanation for the presence of the MnFe site in R2lox: to provide a metal center that is capable of two-electron chemistry, and which is more stable and less sensitive to external reductants than an Fe(IV)Fe(IV) site. PMID- 22083103 TI - Suzuki-Miyaura coupling of heteroaryl boronic acids and vinyl chlorides. AB - A protocol for the Suzuki-Miyaura coupling of heteroaryl boronic acids and vinyl chlorides that minimizes protodeboronation is described. A combination of catalytic amounts of Pd(OAc)(2) and SPhos in conjunction with CsF in isopropanol effectively affords a variety of coupled products. Surprisingly, a dramatic temperature dependence in product selectivity was observed. PMID- 22083104 TI - Ten years of BSE surveillance in Italy: neuropathological findings in clinically suspected cases. AB - Between 2001 and 2010, 244 clinically suspected cases of bovine spongiform encephalopathy (BSE) were reported in Italy. This report summarizes the neuropathological findings in cattle displaying clinical signs consistent with a diagnosis of BSE. All animal specimens were submitted for confirmatory testing; samples testing negative underwent neuropathological examination to establish the differential diagnosis. Immunohistochemistry for scrapie prion protein (PrPSc) at the level of frontal cortex was carried out to exclude atypical BSE. Neuropathological changes were detected in 34.9% of cases; no histological lesions were found in 52.3% of subjects; 12.8% of samples were found unsuitable for analysis. BSE was detected in one case, but no cases of atypical BSE were observed. This study identified the diseases most commonly encountered in the differential diagnosis of BSE; furthermore, it demonstrated that the surveillance system is necessary for monitoring neuropathological disease in cattle and for the detection of BSE cases. PMID- 22083101 TI - Uncovering the role of 5-hydroxymethylcytosine in the epigenome. AB - Just over 2 years ago, TET1 was found to catalyse the oxidation of 5 methylcytosine, a well-known epigenetic mark, into 5-hydroxymethylcytosine in mammalian DNA. The exciting prospect of a novel epigenetic modification that may dynamically regulate DNA methylation has led to the rapid accumulation of publications from a wide array of fields, from biochemistry to stem cell biology. Although we have only started to scratch the surface, interesting clues on the role of 5-hydroxymethylcytosine are quickly emerging. PMID- 22083106 TI - Acetylene and argon adsorption in a supramolecular organic zeolite. AB - The adsorption properties of a new nanoporous organic zeolite with respect to acetylene and Ar were studied by volumetric adsorption analysis, microcalorimetric experiments, and synchrotron high-resolution X-ray powder diffraction. This allowed us to locate the guest molecules inside the host channels and characterize the host-guest interactions. PMID- 22083105 TI - Performance and microbial community dynamics of a sulfate-reducing bioreactor treating coal generated acid mine drainage. AB - The effectiveness of a passive flow sulfate-reducing bioreactor processing acid mine drainage (AMD) generated from an abandoned coal mine in Southern Illinois was evaluated using geochemical and microbial community analysis 10 months post bioreactor construction. The results indicated that the treatment system was successful in both raising the pH of the AMD from 3.09 to 6.56 and in lowering the total iron level by 95.9%. While sulfate levels did decrease by 67.4%, the level post treatment (1153 mg/l) remained above recommended drinking water levels. Stimulation of biological sulfate reduction was indicated by a +2.600/00 increase in delta(34)S content of the remaining sulfate in the water post treatment. Bacterial community analysis targeting 16S rRNA and dsrAB genes indicated that the pre-treated samples were dominated by bacteria related to iron oxidizing Betaproteobacteria, while the post-treated water directly from the reactor outflow was dominated by sequences related to sulfur-oxidizing Epsilonproteobacteria and complex carbon degrading Bacteroidetes and Firmicutes phylums. Analysis of the post-treated water, prior to environmental release, revealed that the community shifted back to predominantly iron-oxidizing Betaproteobacteria. DsrA analysis implied limited diversity in the sulfate reducing population present in both the bioreactor outflow and oxidation pond samples. These results support the use of passive flow bioreactors to lower the acidity, metal, and sulfate levels present in the AMD at the Tab-Simco mine, but suggest modifications of the system are necessary to both stimulate sulfate reducing bacteria and inhibit sulfur-oxidizing bacteria. PMID- 22083107 TI - Skeletal remodeling following clinically relevant radiation-induced bone damage treated with zoledronic acid. AB - Our aim was to determine if zoledronic acid (ZA) changes (45)Ca pharmacokinetics and bone microstructure in irradiated, ovary-intact (I) and irradiated, ovariectomized mice (OVX), two groups with different patterns of skeletal damage. The hind limbs of I and OVX BALB/c mice received a single 16-Gy radiation dose, simulating pre- and postmenopausal female cancer patients undergoing radiation treatment. All I and OVX mice were radiolabeled with 15 MUCi (45)Ca. Mice were treated with or without a 0.5 mg/kg injection of ZA. The time course of bone mineral remodeling was evaluated using a fecal (45)Ca assay, measured by liquid scintillation. A group of nonirradiated, intact mice were used for the longitudinal evaluation of (45)Ca biodistribution. Distal femur bone histomorphometric parameters were measured using microCT at 50 days post-ZA intervention. Most (45)Ca was incorporated into the skeleton and eliminated from the soft tissues within 3-5 days postirradiation, attaining a steady state of excretion at 25-30 days. ZA intervention in both groups resulted in a rapid decrease in fecal (45)Ca excretion. There was a significant difference in (45)Ca excretion in the OVX +/- ZA (P = 0.005) group but not in the I +/- ZA (P = 0.655) group. The rate of excretion of fecal (45)Ca was slower in the OVX + ZA compared to the I + ZA group (P = 0.064). (45)Ca assay is useful to monitor the time course of bone mineral remodeling after an antiresorptive intervention in irradiated mice, providing a basis to investigate bone effects of cancer therapy protocols. For equivalent doses of ZA, recovery may depend on the nature and degree of skeletal damage. PMID- 22083108 TI - Landfill mining: a critical review of two decades of research. AB - Landfills have historically been seen as the ultimate solution for storing waste at minimum cost. It is now a well-known fact that such deposits have related implications such as long-term methane emissions, local pollution concerns, settling issues and limitations on urban development. Landfill mining has been suggested as a strategy to address such problems, and in principle means the excavation, processing, treatment and/or recycling of deposited materials. This study involves a literature review on landfill mining covering a meta-analysis of the main trends, objectives, topics and findings in 39 research papers published during the period 1988-2008. The results show that, so far, landfill mining has primarily been seen as a way to solve traditional management issues related to landfills such as lack of landfill space and local pollution concerns. Although most initiatives have involved some recovery of deposited resources, mainly cover soil and in some cases waste fuel, recycling efforts have often been largely secondary. Typically, simple soil excavation and screening equipment have therefore been applied, often demonstrating moderate performance in obtaining marketable recyclables. Several worldwide changes and recent research findings indicate the emergence of a new perspective on landfills as reservoirs for resource extraction. Although the potential of this approach appears significant, it is argued that facilitating implementation involves a number of research challenges in terms of technology innovation, clarifying the conditions for realization and developing standardized frameworks for evaluating economic and environmental performance from a systems perspective. In order to address these challenges, a combination of applied and theoretical research is required. PMID- 22083109 TI - Toxicity monitoring with primary cultured hepatocytes underestimates the acetaminophen-induced inflammatory responses of the mouse liver. AB - In vitro gene expression profiling with isolated hepatocytes has been used to assess the hepatotoxicity of certain chemicals because of animal welfare issues. However, whether an in vitro system can completely replace the in vivo system has yet to be elucidated in detail. Using a focused microarray established in our laboratory, we examined gene expression profiles in the mouse liver and primary cultured hepatocytes after treatment with different doses of acetaminophen, a widely used analgesic that frequently causes liver injury. The acute hepatotoxicity of acetaminophen was confirmed by showing the induction of an oxidative stress marker, heme oxygenase-1, elevated levels of serum transaminase, and histopathological findings. In vivo microarray and network analysis showed that acetaminophen treatment provoked alterations in relation to the inflammatory response, and that tumor necrosis factor-alpha plays a central role in related pathway alterations. By contrast, pathway analyses in in vitro isolated hepatocytes did not find such prominent changes in the inflammation-related networks compared with the in vivo situation. Thus, although in vitro gene expression profiles are useful for evaluating the direct toxicity of chemicals, indirect toxicities including inflammatory responses mediated by cell-cell interactions or secondary toxicity due to pathophysiological changes in the whole body may be overlooked. Our results indicate that the in vitro hepatotoxicity prediction system using isolated hepatocytes does not fully reflect the in vivo cellular response. An in vitro system may be appropriate, therefore, for high throughput screening to detect the direct hepatotoxicity of a test compound. PMID- 22083110 TI - Elemental and configural olfactory coding by antennal lobe neurons of the honeybee (Apis mellifera). AB - When smelling an odorant mixture, olfactory systems can be analytical (i.e. extract information about the mixture elements) or synthetic (i.e. creating a configural percept of the mixture). Here, we studied elemental and configural mixture coding in olfactory neurons of the honeybee antennal lobe, local neurons in particular. We conducted intracellular recordings and stimulated with monomolecular odorants and their coherent or incoherent binary mixtures to reproduce a temporally dynamic environment. We found that about half of the neurons responded as 'elemental neurons', i.e. responses evoked by mixtures reflected the underlying feature information from one of the components. The other half responded as 'configural neurons', i.e. responses to mixtures were clearly different from responses to their single components. Elemental neurons divided in late responders (above 60 ms) and early responder neurons (below 60 ms), whereas responses of configural coding neurons concentrated in-between these divisions. Latencies of neurons with configural responses express a tendency to be faster for coherent stimuli which implies employment in different processing circuits. PMID- 22083111 TI - Effect of maternal dietary intake on the weight of the newborn in Aligarh city, India. AB - BACKGROUND: This study aimed (1) To record the nutrient intake of the respondents and compare the same with the available recommended dietary allowances (RDA). (2) To assess the correlation between maternal dietary intake and the weight of newborn. MATERIALS AND METHODS: Two hundred and ninety two pregnant women. STUDY AREA: Five hospitals of Aligarh city, Uttar Pradesh. Study Tool and Data Collection: Interview schedule was administered to record information regarding dietary intake and weight of newborn. The data collection was initiated in April 2009 and was completed in March' 2010. DATA ANALYSIS: Statistical analysis was done by using version SPSS 17. Frequency distributions were calculated for all variables. Univariate and multivariate analysis were performed to determine the influence of the dietary intake on the birth weight of newborn. RESULTS: Results revealed that the nutrient intake in all trimesters of pregnancy was lower as compared to RDA. There were significant correlations between the nutrient intake of the mothers and the weight of newborn in all trimesters of pregnancy (P=0.01). CONCLUSION: It was found that the dietary intake during all trimesters of pregnancy were significantly associated with the birth weight. PMID- 22083115 TI - Transplantation: Liver steatosis and errors in estimation of standard liver volume. PMID- 22083118 TI - Pancreas: Limiting EUS misinterpretation of mucus as mural nodules in pancreatic cysts. PMID- 22083120 TI - Colorectal cancer: Fusobacterium nucleatum found in colon cancer tissue--could an infection cause colorectal cancer? PMID- 22083123 TI - Liver: Usefulness of noninvasive biomarkers of fibrosis in chronic liver disease. PMID- 22083124 TI - Pancreas: Oral microbiota and pancreatic disease. PMID- 22083127 TI - New perspectives on photosynthetic phosphorylation in the light of a torsional mechanism of energy transduction and ATP synthesis. AB - New perspectives on photophosphorylation have been offered from the standpoint of the torsional mechanism of energy transduction and ATP synthesis. New experimental data on the involvement of malate anions in ATP synthesis in an acid base malate bath procedure has been reported on spinach chloroplast thylakoids as the model system. The data cannot be reconciled with the chemiosmotic theory but has been shown to be naturally explained by the torsional mechanism. The path of malic acid in the acid and base stages of the experiment has been traced, offering further strong support to the new paradigm. Classical observations in the field have been re-interpreted in the light of these findings. A new concept of ion translocation, energy transduction and coupling at the overall physiological level in photophosphorylation has been presented and a large number of novel experimentally testable predictions have been made and shown to arise as logical consequences of the new perspectives. PMID- 22083126 TI - Mitochondrial pathobiology in ALS. AB - Amyotrophic lateral sclerosis (ALS) is the third most common human adult-onset neurodegenerative disease. Some forms of ALS are inherited, and disease-causing genes have been identified. Nevertheless, the mechanisms of neurodegeneration in ALS are unresolved. Genetic, biochemical, and morphological analyses of human ALS as well as cell and animal models of ALS reveal that mitochondria could have roles in this neurodegeneration. The varied functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations. Changes occur in mitochondrial respiratory chain enzymes and mitochondrial programmed cell death proteins in ALS. Transgenic mouse models of ALS reveal possible principles governing the biology of neurodegeneration that implicate mitochondria and the mitochondrial permeability transition pore. This paper reviews how mitochondrial pathobiology might contribute to the mechanisms of neurodegeneration in ALS. PMID- 22083128 TI - Architecture and characterization of sarcosine oxidase from Thermococcus kodakarensis KOD1. AB - Sarcosine oxidase (SOX) catalyzes the oxidation of the methyl group in sarcosine and transfer of the oxidized methyl group into the one-carbon metabolic pool. Here, we separately cloned and expressed alpha and beta subunit of SOX from Thermococcus kodakarensis KOD1 (TkSOX) in Escherichia coli and the recombinant proteins were purified to homogeneity. Gel filtration chromatography and transmission electron microscopy analysis showed that the alpha subunit formed a dimeric structure and behaved as an NADH dehydrogenase; beta subunit was a tetramer that had sarcosine oxidase and L: -proline dehydrogenase activity. The TkSOX complex assembled into the hetero-octameric (alphabeta)(4) form and had NADH dehydrogenase activity. Gold-label analysis indicated that alpha and beta subunits were oriented in the alternative form. Based on these results, we suggested that TkSOX was a multifunctional enzyme and that each subunit and (alphabeta)(4) complex may separately exist as a function enzyme in different conditions. PMID- 22083129 TI - Temperature responses of growth, photosynthesis, fatty acid and nitrate reductase in Antarctic and temperate Stichococcus. AB - Stichococcus, a genus of green algae, distributes in ice-free areas throughout Antarctica. To understand adaptive strategies of Stichococcus to permanently cold environments, the physiological responses to temperature of two psychrotolerants, S. bacillaris NJ-10 and S. minutus NJ-17, isolated from rock surfaces in Antarctica were compared with that of one temperate S. bacillaris FACHB753. Two Antarctic Stichococcus strains grew at temperature from 4 to 25 degrees C, while the temperate strain could grow above 30 degrees C but could not survive at 4 degrees C. The photosynthetic activity of FACHB753 at lower than 10 degrees C was less than that of Antarctic algae. Nitrate reductase in NJ-10 and NJ-17 had its optimal temperature at 20 degrees C, in comparison, the maximal activity of nitrate reductase in FACHB753 was found at 25 degrees C. When cultured at 4-15 degrees C a large portion of unsaturated fatty acids in the two Antarctic species was detected and the regulation of the degree of unsaturation of fatty acids by temperature was observed only above 15 degrees C, though the content of the major unsaturated fatty acid alphaC18:3 in FACHB753 decreased with the temperatures elevated from 10 to 25 degrees C. Elevated nitrate reductase activity and photosynthetic rates at low temperatures together with the high proportion of unsaturated fatty acids contribute to the ability of the Antarctic Stichococcus to thrive. PMID- 22083130 TI - Cooperative folding of tau peptide by coordination of group IIB metal cations during heparin-induced aggregation. AB - The group IIB elements, especially Cd(II) and Hg(II), are increasingly considered as potential environmental neurotoxins. This study demonstrates that the Alzheimer's tau fragment R2, corresponding to the second repeat of the microtubule-binding domain, can bind to Zn(II), Cd(II) and Hg(II). Isothermal titration calorimetry experiments suggest that the most likely coordination site is the thiol group of Cys291, and this is further confirmed by a control experiment using a C291A mutant peptide. Circular dichroism spectrum reveals that the coordination of group IIB cations, especially Hg(II), can induce pronounced conformational conversions in natively unfolded R2, from random coil to other ordered structures. ThS fluorescence assays and electron microscopy indicate that the group IIB cations promote heparin-induced aggregation of R2, giving relatively small R2 filaments. The efficiency in promoting aggregation, as well as inducing conformational conversion, varies strongly with the cation's polarizability. Based on these results, a model is proposed in which the cooperative folding of R2 through cross-bridging of group IIB cations is suggested to be a key factor in promoting aggregation, in addition to the effective neutralization of coulombic charge-charge repulsion by heparin, the poly-anion inducer. Our results provide clues to understanding the potential pathogenic role of group IIB metals in the development of neurofibrillary tangles, a typical hallmark of Alzheimer's disease. PMID- 22083131 TI - The Phaseolus vulgaris miR159a precursor encodes a second differentially expressed microRNA. AB - Plant microRNAs originate from a stem-loop structured single-stranded RNA precursor. Each stem-loop is processed to generate a mature microRNA that is recruited to an ARGONAUTE-containing multi-protein complex to direct silencing of its target mRNA. Here we report that the conserved plant miR159a precursor produces a second 21-nt long RNA with the properties of a microRNA. Its presence in different plant species is supported by its conservation in the stem-loop position and expression as determined by northern blot analysis. We show that successive processing by DCL1 produces this novel microRNA from the same precursor as miR159a. In contrast to the low levels observed in other plant models for the equivalent of miR159.2, in P. vulgaris, the accumulation of miR159.2 is easily detectable and when compared to miR159a, their expression patterns are distinct in different organs and growth conditions. Further evidence of the functionality of miR159.2 comes from its association with silencing complexes as demonstrated by co-immunoprecipitation experiments using an AGO1 specific antibody and processing of an artificial GFP reporter construct containing a complementary target sequence. These results indicate that the second small RNA corresponds to a microRNA, at least partially independent of miR159 activity, and that in plants a miRNA precursor may encode multiple regulatory small RNAs. PMID- 22083132 TI - Microarray analysis of broad-spectrum resistance derived from an indica cultivar Rathu Heenati. AB - Rathu Heenati (RHT) is a Sri Lankan rice cultivar that carries a brown planthopper (BPH) resistance gene, Bph3, and shows broad-spectrum resistance to all four biotypes of BPH. The BPH-resistance loci in RHT has been studied extensively and assigned to four different rice chromosomes (3, 4, 6, and 10) by different research groups, but the gene has not been cloned previously. An Affymetrix rice genome array containing 48,564 japonica and 1,260 indica sequences was used to analyze the potential resistance-related genes on the four chromosomes by comparative analysis of the differentially expressed genes between resistant and susceptible rice cultivars exposed to BPH attack. The microarray results showed that at least 17 genes related to induced resistance and at least 193 genes related to constitutive resistance in RHT. On chromosome 3, the AOC4 was hypothesized to be the most important candidate gene. On chromosome 6, no valuable candidate resistance gene was identified in the Bph3 localization region. In the three Quantitative trait locus regions of chromosomes 3, 4, and 10, the numbers of constitutive and induced resistance-related genes found were 17, 26, and 12, respectively. The major probe on chromosome 10 represents a constitutive expression gene with a very high absolute fold-change of 2,588.82. The microarray analysis indicated that BPH resistance in RHT is probably controlled by a series of resistance-related genes. This study provides valuable information for cloning, functional analysis and marker-assisted breeding of these BPH resistance genes. PMID- 22083133 TI - An unusual Me3SiI-promoted [4+2] annulation and reduction: an efficient approach to construct 4H-benzopyrans. AB - Me(3)SiI-promoted reaction of salicylic aldehydes with beta-dicarbonyl compounds provided a facile way to construct 4H-benzopyrans in moderate to good yields. This tandem reaction proceeds with high efficiency through nucleophilic addition, silyl enol ether formation, substitution, reduction, and intramolecular nucleophilic cyclization. PMID- 22083135 TI - Silver-catalyzed low-temperature CO isotopic scrambling reaction: 12C16O + 13C18O -> 12C18O + 13C16O. AB - In this paper we report on low-temperature CO isotopic scrambling ((12)C(16)O + (13)C(18)O ->(12)C(18)O + (13)C(16)O). The reaction proceeds on a commercial silver-exchanged zeolite even at about 100 K and requires an optimal reduction degree of the catalysts. PMID- 22083134 TI - New horizons for cholesterol ester transfer protein inhibitors. AB - High-density lipoprotein (HDL) cholesterol levels bear an inverse relationship to cardiovascular risk. To date, however, no intervention specifically targeting HDL has been demonstrated to reduce cardiovascular risk. Cholesterol ester transfer protein (CETP) mediates transfer of cholesterol ester from HDL to apolipoprotein B-containing particles. Most, but not all observational cohort studies indicate that genetic polymorphisms of CETP associated with reduced activity and higher HDL cholesterol levels are also associated with reduced cardiovascular risk. Some, but not all studies indicate that CETP inhibition in rabbits retards atherosclerosis, whereas transgenic CETP expression in mice promotes atherosclerosis. Torcetrapib, the first CETP inhibitor to reach phase III clinical development, was abandoned due to excess mortality associated with increases in aldosterone and blood pressure. Two other CETP inhibitors have entered phase III clinical development. Anacetrapib is a potent inhibitor of CETP that produces very large increases in HDL cholesterol and large reductions in low density lipoprotein (LDL) cholesterol, beyond those achieved with statins. Dalcetrapib is a less potent CETP inhibitor that produces smaller increases in HDL cholesterol with minimal effect on LDL cholesterol. Both agents appear to allow efflux of cholesterol from macrophages to HDL in vitro, and neither agent affects blood pressure or aldosterone in vivo. Two large cardiovascular outcomes trials, one with anacetrapib and one with dalcetrapib, should provide a conclusive test of the hypothesis that inhibition of CETP decreases cardiovascular risk. PMID- 22083137 TI - Reply to the comment by Carmelo Anile on the paper "Complexity analysis of the cerebrospinal fluid pulse waveform during infusion studies". PMID- 22083136 TI - Deficient language acquisition in children with single suture craniosynostosis and deformational posterior plagiocephaly. AB - PURPOSE: This study examined early language acquisition in children with single suture craniosynostosis (SSC) and in children with deformational posterior plagiocephaly. Our purpose was to determine whether infants with SSC have normal language acquisition at the age of 3 years, and whether infants with deformational posterior plagiocephaly demonstrate parallel development when compared with children with SSC. METHODS: The study population includes 61 infants. Twenty of them had synostosis of the sagittal suture, 12 synostosis of other suture and 29 deformational posterior plagiocephaly. Forty-nine of them were operated on a mean age of 10.6 months, and 12 were non-operated children with deformational posterior plagiocephaly. Language skills of participants were prospectively evaluated at the mean age of 3 years 4 months. RESULTS: About one half of the subjects (49%) had normal linguistic development, 30% had slight developmental problems and 21% had severe disorders in speech-language-related skills. These figures showed the prevalence of severe language disorders to be three times higher in our study population when compared with the general population. Children with sagittal synostosis managed better in all language skills compared with other types of SSC. Defective language development was found in deformational posterior plagiocephaly, both operated and non-operated. CONCLUSIONS: We found a noticeable developmental risk for specific language impairment in children with nonsyndromic SSC, and that the deviant language development is observable already in early infancy. Contrary to previous beliefs, the developmental risk for defective language development in deformational posterior plagiocephaly was found in both operated and non-operated subjects. PMID- 22083138 TI - Stem cells: on the front line. PMID- 22083140 TI - Inhibition of GSK3 by Wnt signalling--two contrasting models. AB - The key read-out of Wnt signalling is a change in the transcriptional profile of the cell, which is driven by beta-catenin. beta-catenin levels are normally kept low by a phosphorylation event that is mediated by glycogen synthase kinase 3 (GSK3, alpha- and beta-isoforms), which targets beta-catenin for ubiquitylation and proteasomal degradation. Wnt blocks this phosphorylation event, thereby allowing beta-catenin to accumulate and to co-activate transcription in the nucleus. Exactly how Wnt inhibits GSK3 activity towards beta-catenin is unclear and has been the focus of intensive research. Recent studies on the role of conserved PPPSPxS motifs in the cytoplasmic tail of low-density lipoprotein receptor-related protein (LRP, isoforms 5 and 6) culminated in a biochemical model: Wnt induces the phosphorylation of LRP6 PPPSPxS motifs, which consequently access the catalytic pocket of GSK3 as pseudo-substrates, thus directly blocking its activity against beta-catenin. A distinct cell-biological model was proposed more recently: Wnt proteins induce the uptake of GSK3 into multivesicular bodies (MVBs), an event that sequesters the enzyme away from newly synthesised beta catenin substrate in the cytoplasm, thus blocking its phosphorylation. This new model is based on intriguing observations but also challenges a body of existing evidence, so will require further experimental consolidation. We shall consider whether the two models apply to different modes of Wnt signaling: acute versus chronic. PMID- 22083139 TI - The haematopoietic stem cell niche at a glance. PMID- 22083141 TI - Complications associated with new-onset diabetes after kidney transplantation. AB - New-onset diabetes mellitus after kidney transplantation (NODAT) is widely acknowledged to be associated with increased morbidity and mortality, as well as poor quality of life. Clear evidence links the occurrence of NODAT to accelerated progression of some macrovascular and/or microvascular complications. However, the evidence that some complications commonly attributed to diabetes mellitus occur in the context of transplantation lacks robustness. Certain complications are transplantation-specific and prevalent, but others are not frequently observed or documented. For this reason, it is essential that clinicians are aware of the array of potential complications associated with NODAT in kidney allograft recipients. Rather than simply translating evidence from the general population to the high-risk transplant recipient, this Review aims to provide specific guidance on diabetes-related complications in the context of a complex transplantation environment. PMID- 22083142 TI - A transdisciplinary approach to the selection of moderators of an exercise promotion intervention: baseline data and rationale for Colorado STRIDE. AB - A transdisciplinary approach incorporating biological, psychological, behavioral, and genetic factors was taken to better identify proposed moderators of the effectiveness of an intervention to increase physical activity. This paper illustrates how theory-based individual difference variables can be integrated into a complex randomized controlled trial. The transdisciplinary framework guiding the selection of moderators, the COSTRIDE intervention study and sample, and the relationships among baseline variables are provided. Participants were non-active individuals randomly assigned to either the STRIDE exercise or health and-wellness contact control condition. Structural equation modeling was utilized to demonstrate that relationships among baseline variables confirm hypothesized relationships in the transdisciplinary framework. Preliminary data from COSTRIDE suggest that interventions among sedentary individuals may be more effective if a broader range of factors influencing physical activity are considered. PMID- 22083144 TI - Comparisons of zinc with cadmium in N2S2 coordination and as S-bonded adducts to tungsten carbonyls. AB - The synthesis and characterization of bis-mercaptoethanediazaheptane cadmium(II) is reported and compared to the analogous zinc complex. Of significance is the dimeric form of the [Zn(N(2)S(2))](2) complex achieves penta-coordination about zinc through a bridging thiolate whereas cadmium engages two thiolate as S bridges resulting in hexa-coordination about cadmium within a coordination polymer whose X-ray crystal structure is reported here. In the presence of W(CO)(5), this polymer breaks up, generating dimeric [Cd(N(2)S(2))](2) with two W(CO)(5) units appended to the terminal thiolates, a feat that is not observed for the zinc dimer analogue. The greater thiophilicity of cadmium over zinc is noted in several features of these complexes. PMID- 22083143 TI - Health professional advice for smoking and weight in adults with and without diabetes: findings from BRFSS. AB - Health risk behaviors including smoking and weight-gain can cause and exacerbate chronic diseases like diabetes. Brief provider advice is an effective intervention to reduce risk from these behaviors. However, behavioral advice is provided more often to those who already have a chronic illness when compared with those who are at risk. The purpose of this study is to determine whether the frequency of provider advice for smoking cessation and weight loss varies between overweight or obese smokers with and without diabetes. BRFSS data from a subset of overweight and obese smokers with (n = 848) and without (n = 6,279) diabetes were analyzed to determine differences in reported provider advice. Overweight and obese smokers with diabetes reported receiving more advice for both weight (46.4% vs. 23.4%, P < 0.001) and smoking (84.5% vs. 72.8%, P < 0.001) compared to those without diabetes. Advice for smoking cessation was reported two to three times more often than advice for weight. Nearly a quarter of those with diabetes and almost half of those without reported no receipt of advice about weight. Results indicate that providers are not adequately addressing overweight and obesity in patients with and at risk for diabetes. PMID- 22083145 TI - QTc behavior during exercise and genetic testing for the long-QT syndrome. PMID- 22083147 TI - Iron overload cardiomyopathy in clinical practice. PMID- 22083146 TI - Definition of early repolarization: a tug of war. PMID- 22083148 TI - Atrial fibrillation pathophysiology: implications for management. AB - Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important contributor to population morbidity and mortality. An arrhythmia that is particularly common in the elderly, AF is growing in prevalence with the aging of the population. Our understanding of the basic mechanisms that govern AF occurrence and persistence has been increasing rapidly. This article reviews the basic pathophysiology of AF over a broad range of levels, touching on the tissue mechanisms that maintain the arrhythmia, the relationship between clinical presentation and basic mechanisms, ion channel and transporter abnormalities that lead to ectopic impulse formation, basic models and tissue determinants of reentry, ion channel determinants of reentry, the nature and roles of electric and structural remodeling, autonomic neural components, anatomic factors, interactions between atrial and ventricular functional consequences of AF, and the basic determinants of atrial thromboembolism. We then review the potential implications of the basic pathophysiology of the arrhythmia for its management. We first discuss consequences for improved rhythm control pharmacotherapy: targeting underlying conditions, new atrium-selective drug targets, new targets for focal ectopic source suppression, and upstream therapy aiming to prevent remodeling. We then review the implications of basic mechanistic considerations for rate control therapy, AF ablation, and the prevention of thromboembolic events. We conclude with some thoughts about the future of translational research related to AF mechanisms. PMID- 22083149 TI - Giant intramural left ventricular rhabdomyoma in a newborn. PMID- 22083150 TI - An inverted location of the bicuspid valve disease: a variant of a variant. PMID- 22083151 TI - Advances in the epidemiology of heart failure and left ventricular remodeling. PMID- 22083153 TI - Letter by Falk regarding article, "An unusual heart failure: cardiac amyloidosis due to light chain myeloma". PMID- 22083154 TI - Letter by Anyfanti et al regarding article, "Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: a pilot study". PMID- 22083155 TI - Congenital lipoid adrenal hyperplasia (a rare form of adrenal insufficiency and ambiguous genitalia) caused by a novel mutation of the steroidogenic acute regulatory protein gene. AB - Congenital lipoid adrenal hyperplasia (lipoid CAH) is a rare autosomal recessive disorder of adrenal and gonadal steroidogenesis. It is most frequently caused by mutations in the steroidogenic acute regulatory protein (StAR) gene. Patients with lipoid CAH typically present with adrenal crisis in early infancy, and those with a 46,XY karyotype have female genitalia. However, it has been recently recognized that the phenotype can be quite variable, in that adrenal insufficiency is detected later in life and patients may have partially masculinized or even normal male genitalia. We report a patient assigned and reared as a female with a 46,XY karyotype and with a homozygous intron 2 (c.178+1G>C) splice site mutation of the StAR gene, which is a novel mutation that causes lipoid CAH. Her clinical presentation was somewhat atypical for a patient with classic lipoid CAH, marked by mild masculinization of the genitalia, detectable adrenal steroids at baseline, and ability to tolerate the stress of a surgical procedure with anesthesia without receiving glucocorticoid treatment. CONCLUSION: There is significant phenotypic variability among patients with lipoid CAH. While splice site mutations in the StAR gene lead to premature translational termination, resulting in truncated and non-functional proteins, there is phenotypic variability among patients with such mutations. Our patient appears to have the more atypical phenotype compared to reported patients with similar mutations. The molecular mechanism underlying this heterogeneity remains unclear. PMID- 22083156 TI - Detection of pulmonary arterial morphology in tetralogy of Fallot with pulmonary atresia by computed tomography: 12 years of experience. AB - Our aim was to evaluate the feasibility of using computed tomography (CT) to define the pulmonary artery anatomy in patients with tetralogy of Fallot and pulmonary atresia (TOF-PA). We retrospectively reviewed 110 patients with TOF-PA between 1995 and 2008. Those who received cardiac catheterization and surgery within 3 months of their CT examinations were enrolled. Based on Dr. Somerville's classification, the pulmonary arterial pattern was determined, including identifiable pulmonary trunk (type I), the presence of both left and right pulmonary arteries without trunk (II), only left or right pulmonary artery present (III), and absent intrapericardial pulmonary arteries (IV). The accuracy of both imaging modalities was evaluated with operation findings as the golden standard. The effective radiation doses and adverse events were also recorded. In the 64 eligible patients (median age, 23 months), CT and catheterization demonstrated accurate pulmonary arterial morphology in 60 (60/64) and 53 (53/64) TOF-PA patients, respectively. Thirty-two of 35 type I patients were correctly identified by CT, whereas 26 were correctly identified by catheterization (p = 0.03). Of the 20 type II TOF-PA patients, 19 were diagnosed by CT, whereas 18 were diagnosed by catheterization. CT and catheterization both successfully defined six type III and three type IV patients. The median calculated radiation doses caused by CT and catheterization were 4.5 and 5.6 mSv, respectively (p > 0.05). CONCLUSIONS: For patients with TOF-PA, CT could accurately delineate pulmonary arterial morphology with the same level of accuracy as cardiac catheterization. Therefore, CT can be considered a reasonable diagnostic alternative for such patients. PMID- 22083157 TI - Ambulatory and home blood pressure measurement: complementary rather than competitive methods. PMID- 22083159 TI - A new presentation of the chimeric CYP11B1/CYP11B2 gene with low prevalence of primary aldosteronism and atypical gene segregation pattern. AB - Familial hyperaldosteronism type I is caused by an unequal crossover of 11beta hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, giving rise to a chimeric CYP11B1/CYP11B2 gene (CG). We describe a family carrying a CG with high levels of free 18-hydroxycortisol but low prevalence of primary aldosteronism (PA) and an atypical CG inheritance pattern in a family of 4 generations with 16 adults and 13 children, we measured the arterial blood pressure, serum aldosterone, and plasma renin activity and then calculated the serum aldosterone:plasma renin activity ratio and urinary free 18-hydroxycortisol. We identified the CG by long-extension PCR and predicted its inheritance pattern. The CG was found in 24 of 29 subjects (10 children and 14 adults). In CG+ patients, hypertension and high 18-hydroxycortisol were prevalent (83% and 100%, respectively). High serum aldosterone:plasma renin activity ratio was more frequent in pediatric than adult patients (80% versus 36%; P<0.001). An inverse association between serum aldosterone:plasma renin activity ratio and age was observed (r=-0.48; P=0.018). Sequence analysis identified the CYP11B1/CYP11B2 crossover in a 50-bp region spanning intron 3 of CYP11B1 and exon 4 of CYP11B2. The CG segregation differs from an autosomal disease, showing 100% of CG penetrance in generations II and III. Statistical analysis suggests that inheritance pattern was not attributed to random segregation (P<0.001). In conclusion, we describe a family with an atypical CYP11B1/CYP11B2 gene inheritance pattern and variable phenotypic expression, where the majority of pediatric patients have primary aldosteronism. Most adults have normal aldosterone and renin levels, which could mask them as essential hypertensives. PMID- 22083158 TI - Role of uncoupled endothelial nitric oxide synthase in abdominal aortic aneurysm formation: treatment with folic acid. AB - It has been shown that endothelial NO synthase (eNOS) uncoupling occurs in hypertension and atherosclerosis. However, its causal role in vascular pathogenesis has not been characterized previously. Here, we challenged eNOS preuncoupled hyperphenylalaninemia (hph)-1 mice (deficient in eNOS cofactor tetrahydrobiopterin biosynthetic enzyme GTPCHI) with angiotensin II (Ang II; 0.7 mg/kg per day, 14 days). Both wild-type and hph-1 groups developed hypertension similarly up to day 6 to 7. Thereafter, ~14% of Ang II-infused (0.7 mg/kg per day) hph-1 mice (n=72) started to die suddenly of ruptured abdominal aortic aneurysm (AAA). Among the survivors, 65% developed AAA, resulting in a total morbidity rate of 79%. In contrast, none of the Ang II-infused wild-type mice died or developed AAA. Ang II progressively deteriorated eNOS uncoupling in hph-1 mice while augmenting tetrahydrobiopterin and nitric oxide (NO(.)) deficiencies. The abundance of the tetrahydrobiopterin salvage enzyme dihydrofolate reductase in the endothelium was decreased in hph-1 mice and further diminished by Ang II infusion. Intriguingly, restoration of dihydrofolate reductase expression by oral administration of folic acid or overexpression of dihydrofolate reductase completely prevented AAA formation in Ang II-infused hph-1 mice while attenuating progressive uncoupling of eNOS. Folic acid also attenuated vascular remodeling and inflammation characterized by medial elastin breakdown and augmented matrix metalloproteinase 2 activity and activation of matrix metalloproteinase 9, as well as macrophage infiltration. In conclusion, these data innovatively suggest a causal role of eNOS uncoupling/tetrahydrobiopterin deficiency in AAA formation. Therefore, oral folic acid administration, endothelium-targeted dihydrofolate reductase gene therapy, and perhaps other countermeasures directed against eNOS uncoupling could be used as new therapeutics for AAA. PMID- 22083160 TI - Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome. AB - Hutchinson-Gilford progeria syndrome is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in Hutchinson-Gilford progeria syndrome and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean: 13.00+/-3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and sex-matched controls in the intima-media (P<0.02), near adventitia (P<0.003), and deep adventitia (P<0.01), as was internal carotid artery mean flow velocity (P<0.0001). Ankle-brachial indices were abnormal in 78% of patients. Effective disease treatments may be heralded by normalizing trends of these noninvasive cardiovascular measures. The data demonstrate that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in Hutchinson-Gilford progeria syndrome. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in Hutchinson-Gilford progeria syndrome provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population. PMID- 22083161 TI - Peroxisome proliferator-activated receptor-gamma regulates inflammation and renin angiotensin system activity in the hypothalamic paraventricular nucleus and ameliorates peripheral manifestations of heart failure. AB - Activation of peroxisome proliferator-activated receptor (PPAR)-gamma, a nuclear transcription factor, has been shown to inhibit the production of proinflammatory cytokines and, in peripheral tissues, to downregulate the renin-angiotensin system. PPAR-gamma is expressed in key brain areas involved in cardiovascular and autonomic regulation. We hypothesized that activation of central PPAR-gamma would reduce sympathetic excitation and ameliorate peripheral manifestations of heart failure (HF) by inhibiting central inflammation and brain renin-angiotensin system activity. Two weeks after coronary artery ligation, HF rats received an intracerebroventricular infusion of the PPAR-gamma agonist pioglitazone or vehicle for another 2 weeks. PPAR-gamma expression in the paraventricular nucleus of hypothalamus, an important cardiovascular region, was unchanged in HF compared with sham-operated rats. However, PPAR-gamma DNA binding activity was reduced, nuclear factor-kappaB activity was increased, and expression of proinflammatory cytokines and angiotensin II type-1 receptor was augmented in the HF rats. Mean blood pressure response to ganglionic blockade was greater; plasma norepinephrine levels, lung/body weight, right ventricle/body weight, and left ventricular end diastolic pressure were increased; and maximal left ventricular dP/dt was decreased. All of these findings were ameliorated in HF rats treated with intracerebroventricular pioglitazone, which increased PPAR-gamma expression and DNA binding activity in the paraventricular nucleus of hypothalamus. The results demonstrate that cardiovascular and autonomic mechanisms leading to heart failure after myocardial infarction can be modulated by activation of PPAR-gamma in the brain. Central PPAR-gamma may be a novel target for treatment of sympathetic excitation in myocardial infarction-induced HF. PMID- 22083162 TI - Sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in salt-induced chronic kidney disease. AB - Hypertension is very prevalent in chronic kidney disease and critical for its prognosis. Sympathoexcitation and oxidative stress have been demonstrated to be involved in chronic kidney disease. We have shown previously that sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in the salt-sensitive hypertension model, Dahl salt-sensitive rats. Thus, we investigated whether sympathoexcitation by excessive brain oxidative stress could contribute to arterial pressure elevation in salt-induced chronic kidney disease model rats. Young (3-week-old) male Sprague-Dawley rats were randomly assigned to a uninephrectomy or sham operation and then subjected to either a normal salt (0.5%) or high-salt (8.0%) diet for 4 weeks. The young salt-loaded uninephrectomized rats exhibited sympathoexcitation, hypertension, and renal injury, proteinuria and global glomerulosclerosis together with tubulointerstitial damage. Under urethane anesthesia and artificial ventilation, renal sympathetic nerve activity, arterial pressure, and heart rate decreased to a greater degree in the salt-loaded uninephrectomized rats than in the nonsalt loaded uninephrectomized rats and the salt-loaded or nonsalt-loaded sham-operated rats, when Tempol, a membrane-permeable superoxide dismutase mimetic, was infused acutely into the lateral cerebral ventricle. Oxidative stress in the hypothalamus, measured by lucigenin chemiluminescence, was also significantly greater. Furthermore, in the salt-loaded uninephrectomized rats, antioxidant treatment with chronic intracerebroventricular Tempol decreased sympathetic nerve activity and arterial pressure, which, in turn, led to a decrease in renal damage. Similar effects were elicited by treatment with oral moxonidine, the central sympatholytic agent. In conclusion, sympathoexcitation by brain oxidative stress may mediate arterial pressure elevation in salt-induced chronic kidney disease. PMID- 22083163 TI - Ambulatory versus home versus clinic blood pressure: the association with subclinical cerebrovascular diseases: the Ohasama Study. AB - The usefulness of ambulatory, home, and casual/clinic blood pressure measurements to predict subclinical cerebrovascular diseases (silent cerebrovascular lesions and carotid atherosclerosis) was compared in a general population. Data on ambulatory, home, and casual/clinic blood pressures and brain MRI to detect silent cerebrovascular lesions were obtained in 1007 subjects aged >=55 years in a general population of Ohasama, Japan. Of the 1007 subjects, 583 underwent evaluation of the extent of carotid atherosclerosis. Twenty-four-hour, daytime, and nighttime ambulatory and home blood pressure levels were closely associated with the risk of silent cerebrovascular lesions and carotid atherosclerosis (all P<0.05). When home and one of the ambulatory blood pressure values were simultaneously included in the same regression model, each of the ambulatory blood pressure values remained a significant predictor of silent cerebrovascular lesions, whereas home blood pressure lost its predictive value. Of the ambulatory blood pressure values, nighttime blood pressure was the strongest predictor of silent cerebrovascular lesions. The home blood pressure value was more closely associated with the risk of carotid atherosclerosis than any of the ambulatory blood pressure values when home and one of the ambulatory blood pressure values were simultaneously included in the same regression model. The casual/clinic blood pressure value had no significant association with the risk of subclinical cerebrovascular diseases. Although the clinical indications for ambulatory blood pressure monitoring and home blood pressure measurements may overlap, the clinical significance of each method for predicting target organ damage may differ for different target organs. PMID- 22083164 TI - Council for [corrected] High Blood Pressure Research/InterAmerican Society of Hypertension/International Society of Hypertension: [corrected] first New Investigators Symposium at the High Blood Pressure Research 2011 Scientific Sessions. PMID- 22083165 TI - Conserved water-mediated H-bonding dynamics of catalytic His159 and Asp158: insight into a possible acid-base coupled mechanism in plant thiol protease. AB - Cysteine protease is ubiquitous in nature. Excess activity of this enzyme causes intercellular proteolysis, muscle tissue degradation, etc. The role of water mediated interactions in the stabilization of catalytically significant Asp158 and His159 was investigated by performing molecular dynamics simulation studies of 16 three-dimensional structures of plant thiol proteases. In the simulated structures, the hydrophilic W(1), W(2) and WD(1) centers form hydrogen bonds with the OD1 atom of Asp158 and the ND1 atom of His159. In the solvated structures, another water molecule, W(E), forms a hydrogen bond with the NE2 atom of His159. In the absence of the water molecule W(E), Trp177 (NE1) and Gln19 (NE2) directly interact with the NE2 atom of His159. All these hydrophilic centers (the locations of W(1), W(2), WD(1), and W(E)) are conserved, and they play a critical role in the stabilization of His-Asp complexes. In the water dynamics of solvated structures, the water molecules W(1) and W(2) form a water...water hydrogen bonded network with a few other water molecules. A few dynamical conformations or transition states involving direct (His159 ND1...Asp158 OD1) and water-mediated (His159 ND1...W(2)...Asp158 OD1) hydrogen-bonded complexes are envisaged from these studies. PMID- 22083166 TI - CYP2D6 genotype and dextromethorphan hydroxylation phenotype in an Ecuadorian population. AB - PURPOSE: Cytochrome P450 2D6 (CYP2D6) genotypes and the dextromethorphan/dextrorphan (DXM/DXT) metabolic ratio (MR), which is a marker of CYP2D6 activity, were studied in 118 unrelated healthy Ecuadorians. METHODS: Genotyping of CYP2D6 was performed by amplification of entire CYP2D6 gene by XL PCR for CYP2D6*5 and multiplication alleles and by real time-PCR for CYP2D6 *2, *3, *4, *6, *10, *17, *29, *35, *41, and copy number. The plasma levels of DXM and its metabolite DXT were determined on a high-performance liquid chromatography-UV system. RESULTS: The proportions of non-functional alleles were 0.4, 10.6, 0.8, 2.1, and 0% for CYP2D6*3, *4, *4 * N, *5, and *6, respectively. Genotypically, only one of the subjects (0.9%) was homozygous for two inactive alleles and phenotypically classified as a poor metabolizer (PM). The MRs (mean +/- standard deviation) corresponding to "activity scores" of 0, 0.5, 1, 1.5, 2, and 2.5 were 10.57 (n = 1), 1.63 +/- 0.35 (n = 2), 1.16 +/- 0.74 (n = 29), 1.00 +/- 0.47 (n = 8), 1.24 +/- 0.82 (n = 76), and 1.30 +/- 0.32 (n = 2), respectively. CONCLUSIONS: Our data suggest that only 1% of subjects of this Ecuadorian population were PMs and that none were phenotypically ultrarapid metabolizers, which is in agreement with previous findings in other Amerindian populations. PMID- 22083167 TI - Statins and associated risk of pneumonia: a systematic review and meta-analysis of observational studies. AB - PURPOSE: Statins have potential anti-inflammatory effects, but the association between statin use and lower incidence of pneumonia is unclear. We have therefore performed a systematic review on the risk of pneumonia in statin users versus non users. METHODS: MEDLINE and EMBASE were searched in December 2010 for controlled observational studies that reported on the risk of pneumonia in statin users. We performed a random effects meta-analysis and assessed heterogeneity using the I2 statistic. RESULTS: A total of 451 citations were screened, and ultimately nine studies (4 case-control, 4 retrospective cohort, 1 prospective cohort) with more than 3 million participants were included in the meta-analysis. Pooled analysis of seven studies that reported unadjusted data failed to show a significantly reduced risk of pneumonia [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.84-1.06, p = 0.33, I2 = 79%] in statin users as compared to non-users. However, a significant reduction in the likelihood of pneumonia associated with statin use (n = 8 studies, OR 0.85, 95% CI 0.75-0.97, p = 0.02, I2 = 81%) was found in the meta-analysis of adjusted data. Both analyses were limited by substantial statistical heterogeneity. Sensitivity analysis failed to fully clarify the source of heterogeneity, but cohort studies seemed to be less heterogenous (n = 5 studies, OR 0.92, 95% CI 0.84-1.01, I2 = 43%). CONCLUSION: Our findings indicate that the purported benefit of statins in preventing pneumonia is inconsistent, and of low magnitude, with upper bounds of the confidence interval being close to null. In view of the substantial statistical and clinical heterogeneity in the dataset, there is no convincing evidence to support the therapeutic application of statins for reducing the risk of pneumonia. PMID- 22083168 TI - Mutational analysis of NOG in esophageal atresia and tracheoesophageal fistula patients. AB - PURPOSE: The NOG protein is a secretory antagonist of bone morphogenetic proteins (BMPs). Nog-/- mouse embryos demonstrate proximal esophageal atresia (EA) and distal tracheoesophageal fistula (TEF) compatible with the most common configuration of EA/TEF observed in humans. Four microdeletions that span the NOG locus at 17q22 have been described in human patients having EA/TEF. We investigated the incidence of point mutations in the coding region of the NOG gene in human EA/TEF. METHODS: DNA was collected from 50 patients previously treated for EA/TEF. PCR was used to amplify the coding region of NOG. To detect single nucleotide polymorphisms (SNPs), amplicons were subjected to temperature gradient capillary electrophoresis (TGCE). Candidate SNPs were directly sequenced. RESULTS: TGCE analysis revealed a SNP in the coding region of NOG in 1 of 50 patients (2%). DNA sequencing revealed a synonymous SNP at position 468 (C T) of the NOG coding region. CONCLUSION: SNPs in the coding region of the NOG gene are identified infrequently in human cases of EA/TEF. Further investigation of SNPs in the promoter region of NOG is warranted, as is the effect of synonymous SNPs on NOG mRNA stability. PMID- 22083170 TI - Efficient synthesis of plate-like crystalline hydrated tungsten trioxide thin films with highly improved electrochromic performance. AB - Plate-like hydrated tungsten trioxide (3WO(3).H(2)O) films were grown on a fluorine doped tin oxide (FTO) coated transparent conductive substrate via an efficient, facile and template-free hydrothermal method. The film exhibited a fast coloration/bleaching response (t(c90%) = 4.3 s and t(b90%) = 1.4 s) and a high coloration efficiency (112.7 cm(2) C(-1)), which were probably due to a large surface area. PMID- 22083169 TI - Evolving perspectives in Wilson disease: diagnosis, treatment and monitoring. AB - Wilson disease (WD), the autosomal recessively inherited copper overload disorder, remains a diagnostic and therapeutic challenge. In the last decade, direct sequencing of the affected gene ATP7B became commercially available, but interpretation of the results still requires careful attention. Thus, a combination of tests reflecting the disturbed copper metabolism is needed to make the final diagnosis. Because of the low disease frequency, the existing treatment concepts are not based on controlled trails. Here, recent outcome reports of larger cohort studies challenge the recommended therapies and call for individualized treatment strategies. The notion, that certain medical regimens may either be insufficient to upkeep copper homeostasis or may lead to a clinically relevant overtreatment, demand a continuous monitoring of patients even after decades of therapy. In this article, we review current diagnostic and therapeutic approaches in WD. PMID- 22083171 TI - Density functional theory calculations for two-dimensional silicene with halogen functionalization. AB - The electronic structures and band gaps of silicene (the Si analogue of graphene) adsorbed with halogen elements are studied using the density functional theory based screened exchange local density approximation method. It is found that the band gaps of silicene adsorbed with F, Cl, Br and I have a nonmonotonic change as the periodic number of the halogen elements increases. This is attributed to the transfer of contributions to band gaps from Si-Si bonding to Si-halogen bonding. PMID- 22083172 TI - In the news: Doubt over Azilect(r) relabeling. PMID- 22083173 TI - Epilepsy: Electric source imaging--an inexpensive and reliable method to estimate the epileptic focus. PMID- 22083175 TI - Ultrafast energy transfer pathways in R-phycoerythrin from Polysiphonia urceolata. AB - Energy transfer (ET) processes between chromophores in R-phycoerythrin (R-PE) from Polysiphonia urceolata were studied by use of ultrafast spectroscopic methods. Several primary ET pathways were elaborated. A fluorescence decay component with a time constant of several hundred picoseconds observed by streak camera is tentatively assigned to the reversible formation of exciton traps between alpha84 and beta84 pigment pairs. In order to investigate much faster ET processes in R-PE, a noncollinear optical parametric amplifier based femtosecond time-resolved transient fluorescence spectrometer was employed. The results reveal that the ET between alpha84 and beta84 pigment pair has a time constant of 1-2 ps; the energy migration between alpha84 and beta84 pairs within the R-PE trimer has a time constant of 30-40 ps. We also demonstrated an ET process from phycourobilin to phycoerythrobilin with a time constant as fast as 2.5-3.0 ps, which was directly observed in fluorescence kinetics by selective excitation of the phycourobilin molecules acting as the energy donor. PMID- 22083177 TI - [Genomic imprinting and carcinogenesis]. AB - Genomic imprinting is an epigenetic marking and a stable transmission of monoallelic gene expression patterns in a parent of- origin-specific manner. Aberrant imprinting has been linked to a number of human genetic disorders, including congenital abnormalities, childhood cancer, behavior disorders, and cancer in adults. Imprinted genes play roles in carcinogenesis. Recently, progress in researched on epigenetic mechanisms of imprinted genes, in edition to analysis of the pathology of the oncogenetic mechanisms, has begun to be clinically applied to diagnostic methods, prevention, and cancer drug development. PMID- 22083176 TI - Pathogenic role of effector cells and immunoglobulins in cationic bovine serum albumin-induced membranous nephropathy. AB - Membranous nephropathy (MN) is an autoimmune-mediated glomerulonephritis. The roles of effector cells and immunoglobulins (Igs) in the mediation of glomerular injury in MN have not been fully elucidated. MN was induced by cationic bovine serum albumin (cBSA), and passive disease was induced by transferring effector cells or serum into severe combined immunodeficient (SCID) mice. MN could not be induced in SCID mice. Transfer of serum from MN mice, but not from normal control mice, to SCID mice induced granular immune complex deposits and pathologic proteinuria. Increased immunofluorescent staining for complement, oxidative stress, terminal deoxynucleotidyl transferase-mediated nick end-labeling assay positive cells, and augmented phospho-NF-kappaB staining were evident in the kidneys of MN serum recipients. However, no histological or clinical manifestations were exhibited by SCID mice that received an adoptive transfer of splenocytes. Adaptive immunity was essential for the development of MN. Specific Igs and their subsequent response contribute to the development of renal injury in cBSA-induced MN. PMID- 22083178 TI - [Management of extravasation of chemotherapeutic agents]. AB - Extravasation of chemotherapeutic agents can potentially cause severe skin damage such as ulceration, resulting in a dramatic decrease in quality of life in patients receiving chemotherapy. Although guidelines for treating extravasation were published in Japan a few years ago, practical procedures on how to deal with it, have not been presented in the guidelines yet due to a lack of supporting evidence. Therefore, each hospital should provide its own procedures to manage the extravasation of chemotherapeutic agents. We describe here the treatment of extravasation by topical injection of steroids. We have never experienced significant skin damage in patients after treatment with topical steroid injections. PMID- 22083179 TI - [Infusion reaction and anaphylaxis]. AB - Infusion reactions and allergic reactions are common side effects of anti-cancer drugs, and are known as hypersensitivity reactions. Patients with these severe reactions require close attention because these reactions sometimes lead to critical conditions. Infusion reactions are caused by cytokine release, although the precise mechanisms involved are still obscure. Infusion reactions are often caused by rituximab, an anti-CD20 antibody, and other monoclonal antibodies. Allergic reactions, mediated by IgE, are observed with a variety of chemotherapeutic drugs, especially platinum compounds and taxanes. An acute severe allergic reaction is called anaphylaxis, and is often fatal unless treated appropriately. In this review, we describe the prevention of hypersensitivity reactions and their treatment based on our clinical experience. PMID- 22083180 TI - [Risk management in ambulatory anti-cancer therapy, focusing on nausea and vomiting]. AB - Patients who receive ambulatory-based chemotherapy worry about nausea and vomiting leading to appetite loss, decreased activity, and finally, the lowering of QOL. The management of nausea and vomiting also prevents decreased body weight loss, encourages compliance with chemotherapy treatments, and promotes social activity. Recently, NCCN, ASCO, MASCC as well as JSCO guideline for antiemesis were updated and approved for delayed antiemetic drugs in Japan. According to these guidelines, we should administer antiemetic drugs appropriately to prevent anticipatory emesis. Last year, in a retrospective analysis of head and neck cancer, in a comparison of before and after the use of aprepitant, the use can improved the dose intensity of CDDP and one-year survival after chemotherapy. We need to have prospective analyses, but appropriate use of antiemetic drugs and management of chemotherapy lead to a better clinical outcome and safety. PMID- 22083181 TI - [Chemotherapy-induced stomatitis and diarrhea]. AB - Chemotherapy-induced mucositis is a clinically important and sometimes dose limiting toxicity of cancer treatment, including standard-dose chemotherapy, high dose chemotherapy and chemoradiotherapy. Consequently, dose reductions or treatment delays resulting from mucositis may impair treatment effectiveness. Symptoms are oral mucositis, dysphagia, abdominal pain and diarrhea, depending on the affected site. Although the underlying pathobiology of oral mucositis has been considerably elucidated over the past decade, there are few interventions for the prevention or treatment validated by randomized trials. The most commonly accepted intervention is basic oral care. Diarrhea is most common in patients treated with irinotecan and in some cases, life-threatening. No definitive interventions for the prevention of diarrhea exist, but there is evidence that loperamide and octreotide are effective for chemotherapy-induced diarrhea. In future, there is a need for well designed trials, preferably including a placebo or no treatment control, validating more effective interventions for managing chemotherapy- induced mucositis. PMID- 22083182 TI - [Skin toxicity]. AB - It has been suggested that skin symptoms may cause psychological distress associated with change in appearance, and affect patients' quality of life(QOL). Also, there is a correlation between the severity of skin disorder resulting from treatment with epidermal growth factor receptor(EGFR)inhibitors(cetuximab, panitumumab, erlotinib)and their clinical effects. Treatment with EGFR inhibitors needs to be continued as long as possible while treatment-related skin symptoms are managed appropriately. Adherence to this approach will benefit the patients. Daily self-skin care(keeping the skin surface clean, maintaining moisture retention, and preventing irritation)is the most important countermeasure for hand-foot syndrome resulting from oral administration of fluorinated pyrimidine anticancer drugs(capecitabine, S-1). An early introduction of effective countermeasures including dose reduction/establishment in the rest period is essential for management of such syndrome. PMID- 22083183 TI - [Chemotherapy-induced peripheral neuropathy]. AB - Chemotherapy-induced peripheral neuropathy(CIPN)is one of chemotherapy's common and disabling adverse effects. It may be caused by many chemotherapeutic agents including the taxanes(paclitaxel, docetaxel), the vinca alkaloids(vincristine, vinorelbine, vinblastine), the platinum analogues(cisplatin, carboplatin, oxaliplatin), bortezomib and thalidomide, among others. Once the symptoms have developed, they may lead to compromising patients' quality of life(QOL). For medical oncologists, the management of CIPN remains an important challenge. At the present time, no agent has shown enough solid beneficial evidence to be recommended for the treatment or/prophylaxis of CIPN. The standard of care for CIPN includes awareness and early detection of neuropathy, and dose reduction and/or discontinuation of the problematic agents. PMID- 22083184 TI - [The strategy for chemotherapy-induced myelosuppression]. AB - Myelosuppression is one of the most serious adverse effects induced by chemotherapy targeting solid tumors and hematological malignancies, and results in neutropenia, anemia and thrombocytopenia. In particular, prompt and appropriate treatments are required for febrile neutropenia, because that disease may be fatal. PMID- 22083185 TI - [Interstitial pneumonitis]. AB - The risk management of interstitial pneumonitis in cancer chemotherapy not only involves an adverse event by an anticancer drug, but there are four steps with the incidence of interstitial pneumonitis: 1 ) the time before chemotherapy treatment, selection of chemotherapy regimens and patients, 2 ) the time chemotherapy treatment is performed, 3 ) the time during following-up, 4 ) the time when interstitial pneumonitis occurs. It is necessary to decrease the risk of interstitial pneumonitis by several steps, cooperating with an entire medical staff. PMID- 22083186 TI - [A review of toxicity superselective intra-arterial concurrent chemoradiotherapy(SIACC)for oral cancer]. AB - Superselective intra-arterial concurrent chemoradiotherapy(SIACC)for oral cancer has been favored for its efficacy and ability to not damage organs. SIACC was applied to 13 previously untreated patients with oral cancer for the purpose of avoiding surgical resection of the primary tumor in our hospital from 2007 to 2009. Although a complete response of the primary tumor was achieved in all cases, various adverse events also occurred. All patients experienced leucopenia, and most patients suffered from mucotitis and dry mouth. One patient had dizziness and nausea due to the catheter insertion into the vertebra artery. Although SIACC is an important treatment strategy for oral cancer, careful attention for adverse events should be taken into account during and after treatment. PMID- 22083187 TI - [T2 laryngeal cancer study in our department]. AB - Laryngeal cancer is the most common malignant tumor in the head and neck region.Because early detection and treatment are possible, outcomes are relatively good.Many studies have reported on the treatment of laryngeal cancer.Different hospitals have used generally similar treatment regimens.However, factors such as laryngeal preservation and the treatment of choice for patients with T2 laryngeal cancer still differ among hospitals.Survival rates can be increased depending on treatment, sometimes at the cost of losing voice functions that could have been preserved.In our department, we have emphasized curative treatment and the preservation of organs and functions.We have mainly used chemoradiotherapy concurrently with S-1 and nedaplatin for the treatment of T2 laryngeal cancer.We studied 27 patients(23 men and 4 women)with T2 laryngeal cancer, who received first-line therapy in our department from April 2005 through March 2010. Their mean age was 64.1 years(range, 42 to 80).The mean follow-up period was 30.6 months(range, 2 to 60 months).The tumor-nodemetastasis classification was T2N0M0 in 24 patients, T2N1M0 in 1, and T2N2bM0 in 2.In our department, the disease-specific survival rate was 96.3%. The complete response rate was 88.9%, and the laryngeal preservation rate was 92.6%. PMID- 22083188 TI - [Retrospective analysis of pemetrexed plus cisplatin chemotherapy for elderly advanced non-small-cell lung cancer]. AB - BACKGROUND: The efficacy of pemetrexed(PEM)plus cisplatin(CDDP)therapy for chemotherapy-naive non-squamous cell lung cancer has been reported, but the effectiveness of such a regimen for elderly patients is unknown. PURPOSE: The aim of this study is to examine the efficacy and toxicity of CDDP plus PEM therapy for elderly patients, retrospectively. METHODS: We performed a retrospective analysis of six patients 75 years old or older with non-squamous lung cancer, who underwent CDDP plus PEM therapy from June 2009 to May 2010. RESULTS: The mean age was 79. 2 years old(range, 76-82), gender: 3 males/3 females; stage: III B/IV; 1/5, pathology: all patients had adenocarcinoma without epidermal growth factor receptor (EGFR)mutation, line: first/third; 5/1. The scheduled chemotherapy of four courses was completed in four patients. The overall response rate was 50%, and the disease control rate was 83%. Grade 3/4 neutropenia and thrombocytopenia were observed in 1/2 and 1/1 patients, respectively, but no blood transfusions were needed. Severe myelosuppression was shown in patients who were impaired in renal function. Grade 3 nausea or anorexia was also observed in 50%of patients. Therefore, two patients were terminated in one courses of therapy and long-term hospitalization for them was needed. CONCLUSION: Although CDDP plus PEM therapy for elderly patients has sufficient patients compliance because of its tolerable myelosuppression, it is necessary to pay attention to deterioration in renal function and to care for nausea during chemotherapy. PMID- 22083189 TI - [S-1-based chemotherapy for unresectable advanced gastric cancer of the elderly or patients with renal dysfunction]. AB - OBJECTIVE: S-1 based therapy is a valued standard chemotherapy regimen for unresectable gastric cancer in Japan. S-1/ CDDP therapy has been highly effective, especially for patients under 75 years old who have good organ function. However, it is the elderly and/or patients with renal dysfunction who make up the majority of the candidates for chemotherapy in general hospitals. These factors make it difficult to apply the results of RCTs to chemotherapy regimens. AIM AND METHODS: To investigate clinical outcomes, the medical records of patients who had received S-1 based chemotherapy for gastric cancer at our hospital from January 2002 to September 2009 were retrospectively reviewed. RESULTS: A total of 78 patients were evaluated for analyses. Among the patients, 23(29%)were the elderly, 8(10%)had renal dysfunction, and 27(35%)were either the elderly or those who had renal dysfunction. S-1/CDDP therapy was provided for 63% of the patients. Regarding the outcomes from therapy, RR was 44%, mPFS was 5. 4 months, and MST was 10. 6 months. Regarding survival benefit for OS, the elderly, the intestinal type, and therapy with S-1 alone were considered to be good factors in multi-variant analysis, but no significant differences were confirmed. CONCLUSION: In general practice, the elderly and/or patients with renal dysfunction account for 35%, and S-1-based chemotherapy has been proven to be very effective. However, additional effects of CDDP were not shown in this study. PMID- 22083190 TI - [The feasibility of oral fluoropyrimidines as adjuvant chemotherapy after resection and local coagulation therapy of colorectal liver metastases]. AB - OBJECTIVE: To evaluate the feasibility of oral fluoropyrimidines after resection and microwave coagulation(MCT), or radiofrequency ablation(RFA)of liver metastases from colorectal cancer. PATIENTS AND METHODS: Background factors, fluoropyrimidine administration(S-1 or UFT/LV), and adverse events were analyzed in 20 patients(17 males, 3 females; an average of 62. 4 years)with colorectal liver metastases after resection and RFA or MCT. RESULTS: The synchronous: metachronous metastases ratio was 13:7. Fifteen patients received the recommended dose and 5 received a reduced dose. S-1 was administered for 4 weeks followed by a 2-week rest for 7 patients, and for 2 weeks followed by a 1-week rest for 9 patients. UFT/LV was administered for 4 weeks followed by a 1-week rest for 4 patients. Fourteen patients(70%)had adverse events. One patient showed grade 3 leukocyte toxicity while other patients showed grade 1 or 2. Two patients discontinued chemotherapy because of grade 2 delirium and grade 2 CPK elevation; another 2 discontinued voluntarily. Eight patients with recurrence changed the rugs, while 8 of 12(67%)continued for 1 year. Median disease-free and med ian overall survival lengths were 16. 1 and 4 7. 6 months, respectively. CONCLUSION: S-1 and UFT /LV were used safely as adjuvant chemotherapies after the resection and local coagulation therapy of liver metastases. PMID- 22083191 TI - [High-throughput screening method of KRAS mutations at codons 12 and 13 in formalin-fixed paraffin-embedded tissue specimens of metastatic colorectal cancer]. AB - Clinical studies overseas using the therapeutic anti-EGFR monoclonal antibodies, cetuximab or panitumumab against metastatic colorectal cancer(mCRC), have revealed KRAS mutations as a negative predictive marker of response. Accordingly, the Ministry of Health, Labour and Welfare in Japan approved medical reimbursement of the KRAS mutation test in April 2010. Anti-EGFR monoclonal antibody therapies are now used as first-line treatment for patients with mCRC. To advance the simple high-throughput KRAS mutation test, we established a high throughput screening system for detecting KRAS mutations utilizing Luminex(xMAP)technology(the fluorescent bead-based multiplex analyte profiling method), in combination with the polymerase chain reaction-reverse sequence specific oligonucleotide method. Here we evaluated the basic performance of our system and confirmed its high specificity and reproducibility in detecting KRAS mutations at codons 12 and 13 in both plasmid DNAs carrying mutant KRAS genes and formalin-fixed paraffin-embedded tissues from mCRC patients. We demonstrated the KRAS mutation status in paraffin-embedded tissues of mCRC and confirmed that the results were comparable to those of the direct sequencing method. Our high throughput method has an advantage in simultaneous analysis of multiple mutations in one well of 96-well PCR plates, and will advance the KRAS mutation test in clinical laboratories. PMID- 22083192 TI - [The impact of systematic lymphadenectomy for early-stage ovarian carcinomas]. AB - Among the 161 cases of pT1 ovarian cancer treated at our hospital during the last 25 years, the impact of systematic lymphadenectomy was evaluated in 93 cases of the pT1N0M0 group(N0 group), 59 cases of the pT1NxM0(Nx group), and 9 cases of the pT1N1M0(N1 group). Significantly greater relapse-free survival(RFS)and overall survival(OS)were observed in 108 cases of the N0+N1 group compared to the Nx group(p=0. 006, p=0. 02). Multivariate analysis showed that systematic lymphadenectomy was a significant prognostic factor(hazard ratio 0. 473(95%CI, 0. 235-0. 951; p=0. 036). The present study suggested the systematic lymphadenectomy had a significant therapeutic effect on pT1 stage ovarian cancers. PMID- 22083193 TI - [Clinical analyses of oral squamous cell carcinoma patients showing a complete response to chemotherapy with S-1 alone]. AB - The purpose of this study was to investigate the effectiveness and safety of palliative chemotherapy using S-1 alone. We clinically analyzed 8 oral squamous cell carcinoma patients showing a complete response(CR)to chemotherapy with S-1 alone. These patients received chemotherapy consisting of 2 weeks' administration, including 5-days' administration and 2- days' termination, following a 1-week rest. Adverse effects were observed in 4 patients. However, all of them were grade 1 toxicities. The average length of S-1 administration before achieving CR was 9. 8 +/- 3. 1 weeks(3. 3 +/- 1. 0 courses). Seven patients had a recurrence. The prognosis of this group was 5 deaths by local recurrence, and 1 death by lymph node metastasis. The average length of disease progression was 447. 4 +/- 479. 5 days. Two patients, one who received surgery and the other who received irradiation after chemotherapy by S-1, are alive without tumors. The 1-year and 3-year disease-free survival rates were 100% and 37. 5%, respectively. PMID- 22083194 TI - [A case of esophageal cancer with intramural metastasis demonstrates a good clinical course after induction chemotherapy followed by chemoradiation]. AB - A 63-year-old man with dysphagia visited our hospital in February 2007. Esophagogastroduodenoscopy and computed tomography revealed that he suffered from advanced esophageal cancer with intramural metastasis at clinical stage III (T3N1). The patient underwent induction chemotherapy because he had great difficulty deciding which treatment would be more beneficial for him use dash surgery or chemoradiation. The reason for his in decision was that esophageal cancer with intramural metastasis is known to have a poor prognosis after surgery, and although chemoradiation is the more attractive therapy that avoids invasive surgery, it is very difficult to predict a response. Currently, he has survived for more than 3 years with no recurrence, after chemoradiation that followed a good response to induction chemotherapy. This result suggested that induction chemotherapy followed by chemoradiation can be one of the useful strategies for patients who have esophageal cancer with a negative prognosis factor for surgery, such as intramural metastasis. PMID- 22083195 TI - [A case of recurrent lymph node metastases of advanced colon cancer with penetration of the gastric wall, treated effectively by cetuximab monotherapy as third-line treatment]. AB - A 45-year-old man was first treated for lymph node metastases of colon cancer with FOLFIRI. After 13 courses, the lymph node metastases worsened, and he was treated with mFOLFOX6 plus bevacizumab as the second-line chemotherapy. After 8 courses, his anorexia and anemia became increasingly troublesome. We diagnosed this as the direct invasion of lymph node metastases to the gastric wall. As the third-line chemotherapy, cetuximab monotherapy was applied. The gastric ulcer lesion then began healing as a scar. In our progressive case, cetuximab monotherapy was effective as a third-line treatment. PMID- 22083196 TI - [A successful treatment of conversion chemotherapy by mFOLFOX6 plus cetuximab for initially unresectable synchronous colorectal liver metastases]. AB - A 63-year-old woman with a synchronous huge colorectal liver metastasis was referred to our institution.The lesion was technically diagnosed unresectable because the estimated future remnant liver volume was insufficient due to the invasion of the three hepatic veins and hepatic hilum.She underwent 7 courses of mFOLFOX6 and 14 administrations of cetuximab as conversion chemotherapy.Periodic abdominal CT scans revealed the tumor becoming PR, and she was free of cancer invasion to the left hepatic vein.After the remainder of chemotherapy lasting 4 weeks, right trisectionectomy and combined partial resection of the inferior vena cava and primary closure was performed.The postoperative course was uneventful and the patient was discharged at 20 days after the operation.She underwent chemotherapy postoperatively, and then underwent laparoscopic sigmoidectomy.A conversion chemotherapy using cetuximab may contribute to ward rapidly reducing tumor size and improving the resectability of initially unresectable huge colorectal liver metastases, thus leading to prolonged survival. PMID- 22083197 TI - [Synchronous double cancer of the gallbladder and rectum successfully treated with S-1 as second-line chemotherapy- a case report]. AB - A 66-year-old man was referred to our hospital with obstructive jaundice. Computed tomography(CT)scan showed thickening of the gallbladder wall, invasion into the liver bed, and thickening of the rectal wall. Colonoscopy revealed a type 2 rectal cancer, in which adenocarcinoma was identified by endoscopic biopsy. He was diagnosed with double-cancer of the gallbladder and rectum. Because his gallbladder cancer was more life threatening than his rectal cancer, gemcitabine was administered at 1, 000 mg/m2 on days 1, 8, and 15 of a 28-day course. After 3 courses of gemcitabine, the CT scan showed that the lymph nodes in the hepatoduodenal ligament had been enlarged, and duodenal stenosis had occurred as a result of gallbladder cancer invasion. S-1 was administered orally at doses of 120 mg/day twice daily on days 1-28 of a 42-day course. Partial response was confirmed by CT scan. After 8 courses of S-1, the gallbladder cancer had progressed and liver metastases had appeared. He subsequently died of disease progression. He survived for 17 months after the first course of chemotherapy, and the progression-free survival with S-1 was 10 months. Therefore, S-1 could be an effective agent for synchronous double cancer of the gallbladder and rectum. PMID- 22083198 TI - [A case of the usage of entecavir to prevent hepatitis B virus reactivation during chemotherapy in breast cancer patient]. AB - Hepatitis B virus(HBV)reactivation is a serious clinical problem for HBV infected patients, and one of its possible causes is chemotherapy for malignant disease. At the onset of active hepatitis, planned chemotherapy should be discontinued and acute or fetal fulminant hepatitis must be induced in some cases. Therefore, it is desirable to prevent virus reactivation during chemotherapy in HBV-positive patients. We report a case in which adjuvant chemotherapy for a breast cancer patient was accomplished safely by using entecavir. The patient was a 48-year-old woman with breast cancer whose HBV infection had been pointed out when she was 20 years old. Breast reconstruction was performed, followed by mastectomy. Pathological findings were invasive ductal carcinoma, three positive nodes, estrogen and progesterone receptor-positive, and HER2-negative. An adjuvant chemotherapy with anthracycline followed by taxane was planned. Blood chemistry revealed the seroconversion of HBV and the quantity of HBV-DNA was 2. 8 log copies/mL. Administration of the anti-virus agent, entecavir, was started three weeks before chemotherapy. The HBV-DNA was decreased under the titer of detection and no re-increase in HBV-DNA was found during chemotherapy. Planned chemotherapy was accomplished safely without HBV reactivation. PMID- 22083199 TI - [A case of pagetoid carcinoma of the breast in nearly complete response by primary systemic therapy]. AB - A 62-year-old female presented with an erosion of the left nipple. At the preoperative examination, it was diagnosed as a Pagetoid carcinoma with an invasive carcinoma. After primary systemic therapy(weekly paclitaxel/trastuzumab), we performed an operation. The only remaining Paget cell was confirmed in the resected specimen, and no other malignant cells were confirmed. There is no report that the preoperative chemotherapy for the Pagetoid carcinoma with an invasive carcinoma. The patient has had no evidence of recurrence 1. 5 years after the operation. PMID- 22083200 TI - [A case report-bleeding from the ulcer of wound for mastectomy after postoperative chemotherapy with bevacizumab for Sigmoid colon cancer]. AB - We report the case of a 65-year-old woman with a delayed radiation ulcer and bleeding caused by bevacizumab. She has been undergoing chemotherapy for advanced colon cancer for two years. She received a mastectomy and adjuvant chemoradiotherapy for right breast cancer twenty-one years ago, and colon cancer with liver metastasis was detected using PET two years ago. Since last year she has been treated with bevacizumab chemotherapy bevacizumab due to increased liver metastases. As a result, her radiation ulcer worsened and bleeding occurred repeatedly. On suspicion of an adverse event, we stopped the bevacizumab, and that improved the radiation ulcer and the bleeding. In this case, we discussed radiation induced ulcers, wound healing, and adverse events caused by bevacizumab. PMID- 22083201 TI - [A case of repeated bone metastases of breast carcinoma successfully treated by S 1 chemotherapy]. AB - We report a case of breast carcinoma with repeated recurrences in the right bone. The recurrent site of the bone was treated by radiation therapy with a total of 3 7. 5 Gy irradiation, and chemotherapy with the CMF regimen. After 2 years, recurrence was suspected in the same region because there was an elevation of the NCC-ST-439 tumor marker. We carried out chemotherapy with S-1 100mg/body/day. The NCC-ST-439 value returned to within the normal range after 3 months' administration of S -1, and continued in the normal value for 20 months. PMID- 22083202 TI - [A case of lung cancer showing marked reduction of pleural effusion by bevacizumab in combination with carboplatin and paclitaxel]. AB - A 63-year-old man was admitted to our hospital because of dyspnea. Chest computed tomographic(CT)scans showed right pleural effusion. He was diagnosed with adenocarcinoma of the lung(cTXN2M1a, stage IV). Although combination chemotherapy with 80 mg/m / 2 cisplatin(CDDP)and 60 mg/m2 docetaxel hydrate(DOC)was performed for 3 courses, the pleural effusion increased. As he had a progressive disease, his chemotherapy was changed to a new combination of AUC5 carboplatin(CBDCA), 200mg/m / 2 paclitaxel(PTX)and 15 mg/kg bevacizumab. After 2 courses, the pleural effusion dramatically decreased. During 6-month follow-up after the initial consultation, there has been no exacerbation. PMID- 22083203 TI - [Hypercalcemia associated with parathyroid hormone-related protein(PTHrP)in a patient with diffuse large- type B-cell lymphoma(DLBCL)]. AB - We report a patient with diffuse large-type B-cell lymphoma showing hypercalcemia and a raised PTHrP serum level. He was a 72-year-old man with a history of multiple bone fractures due to a traffic accident 3 month ago, and was transferred to our hospital for further evaluation of a hepatic mass and for his rapidly deteriorating general condition. He had been in good health until about 2 weeks ago, but he developed dehydration, azotemia, lethargy, and altered mentality on admission. Laboratory tests revealed hypercalcemia of1 5. 3mg/dL. The hypercalcemia was associated with a high plasma concentration of PTHrP, whereas the parathyroid hormone(PTH-C)was undetectable. After forced hydration and administration of furocemide and calcitonin, hypercalcemia was improved. CT and MRI imaging showed para-aortic lymphadenopathy and a huge mass involving most of the light hepatic lobe and spleen. The pathological diagnosis at liver biopsy was DLBCL. He received six courses of chemotherapy with R-CHOP and is now stable. There was no recurrence of hypercalcemia or an elevation of PTHrP serum level during chemotherapy. The existence of PTHrP produced by tumor cells was suspected, and may have been related to the hypercalcemia in our case. PMID- 22083204 TI - [A case of intravascular large B-cell lymphoma associated with transverse myelopathy]. AB - We present a 68-year-old man suffering from transverse myelopathy since May 2010. The spinal cord MRI showed a T2- hyperintense lesion invading the Th5 level spinal cord. Although the patient transiently responded to steroid-pulse therapy, his neurological symptoms degenerated three months after wards. On admission, he had an apparent hepatosplenomegaly, but no lymphadenopathy. A laboratory examination revealed bicytopenia and increased levels ofLDH and soluble IL-2 receptors. Histological analysis ofa skin biopsy specimen demonstrated proliferation of large atypical lymphoid cells positive for CD20 and CD79a in the small capillaries, leading to our diagnosis of intravascular large B-cell lymphoma(IVLBCL). Thus, the patient's progressive myelopathy was probably caused by IVLBCL invasion. The patient responded well to Rituximab-combined CHOP therapy(R-CHOP), and his neurological symptoms improved immediately. A spinal cord MRI showed the disappearance of the abnormal signal after two courses of R CHOP. IVLBCL often presents with neurological manifestations, including transverse myelopathy. PMID- 22083205 TI - [Problems and potential solutions of regional palliative care: a trial of the multiregional and multidisciplinary conference in the OPTIM study]. AB - Quality palliative care is required at the community level, and interaction among multidisciplinary practitioners from various regions might be useful for improving community palliative care. The aims of the present study are: 1)to evaluate the participant's-perception of the usefulness of the interactive conference of multidisciplinary multiregional healthcare practitioners, and 2)to clarify the areas needing to be improved in community palliative care, raised in the conference. A total of 336 multidisciplinary practitioners from 4 areas of Japan participated in the conference. Overall, more than 80% of the participants evaluated the conference as very useful or useful; more than half reported that the conference was very useful or useful to obtain a concrete solution for the obstacles and to utilize the lessons though the conference as a means to improve quality of care in their own community. The identified areas needing improvement are: 1)developing an interactive networking among healthcare practitioners and/or organizations in the community; 2)developing a system of high quality, easily available specialized palliative care service; 3)improving the knowledge and perception of medical professionals concerning palliative care and home care; 4)developing a collaborative care system between hospitals and community healthcare practitioners and/or organizations; 5)developing a collaborative care system among community healthcare practitioners and/or organizations; 6)optimizing existing resources available in the community; 7)improving the perception of patients and the general public about palliative care, home care, and cancer; and 8)to reevaluate the regulations, laws, healthcare system, and financial or human resources at the social level. PMID- 22083206 TI - Suppression of antigen-specific CD4+ T cell activation by SRA/CD204 through reducing the immunostimulatory capability of antigen-presenting cell. AB - Pattern recognition scavenger receptor SRA/CD204, primarily expressed on specialized antigen-presenting cells (APCs), including dendritic cells (DCs) and macrophages, has been implicated in multiple physiological and pathological processes, including atherosclerosis, Alzheimer's disease, endotoxic shock, host defense, and cancer development. SRA/CD204 was also recently shown to function as an attenuator of vaccine response and antitumor immunity. Here, we, for the first time, report that SRA/CD204 knockout (SRA(-/-)) mice developed a more robust CD4(+) T cell response than wild-type mice after ovalbumin immunization. Splenic DCs from the immunized SRA(-/-) mice were much more efficient than those from WT mice in stimulating naive OT-II cells, indicating that the suppressive activity of SRA/CD204 is mediated by DCs. Strikingly, antigen-exposed SRA(-/-) DCs with or without lipopolysaccharide treatment exhibited increased T-cell-stimulating activity in vitro, which was independent of the classical endocytic property of the SRA/CD204. Additionally, absence of SRA/CD204 resulted in significantly elevated IL12p35 expression in DCs upon CD40 ligation plus interferon gamma (IFN gamma) stimulation. Molecular studies reveal that SRA/CD204 inhibited the activation of STAT1, mitogen activated protein kinase p38, and nuclear factor kappa B signaling activation in DCs treated with anti-CD40 antibodies and IFN gamma. Furthermore, splenocytes from the generated SRA(-/-) OT-II mice showed heightened proliferation upon stimulation with OVA protein or MHC-II-restricted OVA(323-339) peptide compared with cells from the SRA(+/+) OT-II mice. These results not only establish a new role of SRA/CD204 in limiting the intrinsic immunogenicity of APCs and CD4(+) T cell activation but also provide additional insights into the molecular mechanisms involved in the immune suppression by this molecule. PMID- 22083207 TI - In response to "Prenatal screening of sialic acid storage disease and confirmation in cultured fibroblasts by LC-MS/MS" by van den Bosch et al. PMID- 22083208 TI - Predictors of impaired renal function among HIV infected patients commencing highly active antiretroviral therapy in Jos, Nigeria. AB - BACKGROUND: Kidney disease is a common complication of human immunodeficiency virus (HIV) infection even in the era of antiretroviral therapy, with kidney function being abnormal in up to 30% of HIV-infected patients. We determined the predictors of impaired renal function in HIV-infected adults initiating highly active antiretroviral therapy (HAART) in Nigeria. MATERIALS AND METHODS: This was a retrospective study among HIV-1 infected patients attending the antiretroviral clinic at the Jos University Teaching Hospital (JUTH), between November 2005 and November 2007. Data were analysed for age, gender, weight, WHO clinical stage, CD4 count, HIV-1 RNA viral load, HBsAg and anti-HCV antibody status. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Statistical analysis was done using Epi Info 3.5.1. RESULTS: Data for 491 (294 females and 197 males) eligible patients were abstracted. The mean age of this population was 38.8+/-8.87 years. One hundred and seventeen patients (23.8%; 95% CI, 20.2-27.9%) had a reduced eGFR (defined as <60 mL/min), with more females than males (28.6% vs. 16.8%; P=0.02) having reduced eGFR. Age and female sex were found to have significant associations with reduced eGFR. Adjusted odds ratios were 1.07 (95% CI, 1.04, 1.10) and 1.96 (95% CI, 1.23, 3.12) for age and female sex, respectively. CONCLUSIONS: Older age and female sex are independently associated with a higher likelihood of having lower eGFRs at initiation of HAART among our study population. We recommend assessment of renal function of HIV infected patients prior to initiation of HAART to guide the choice and dosing of antiretroviral drugs. PMID- 22083209 TI - The natural plant product sophocarpine ameliorates dextran sodium sulfate-induced colitis in mice by regulating cytokine balance. AB - INTRODUCTION: Sophora alopecuroides L., a traditional Chinese herbal remedy, has been widely used for treating enteritis and bacillary dysentery for many years. Sophocarpine is a major ingredient of S. alopecuroides L. and has a wide range of pharmacological effects. MATERIALS AND METHODS: In this study, we investigated the therapeutic potential of sophocarpine for treating dextran sulfate sodium (DSS)-induced experimental ulcerative colitis in C57BL/6 mice, a well characterized murine model of ulcerative colitis. Experimental colitis was induced in these mice by dissolving 5% DSS in their drinking water for 7 days and sophocarpine (60, 30, and 15 mg/kg of body weight) and sulfasalazine (520 mg/kg) were administered orally once a day for 7 days. RESULTS: Sophocarpine significantly ameliorated DSS-induced colitis as identified by a reduced disease activity index and wet weight of colons as well as recovery of body weight. Furthermore, the oral administration of sophocarpine significantly decreased myeloperoxidase activity and the level of interleukin (IL)-1 and IL-6 in serum (P < 0.01), while there was no significant effect on the level of IL-4. CONCLUSIONS: In conclusion, sophocarpine significantly ameliorated DSS-induced colitis in mice by regulating the pro- and anti-inflammatory cytokine production. Based upon our results, we suggest that sophocarpine is an effective agent for treating colonic inflammation. PMID- 22083210 TI - Functional analysis of protein targets by metabolomic approaches. AB - Proteomics methods, such as activity-based protein profiling, can be used to connect proteins to biology and disease. Some proteins found through unbiased methods are not well characterized, which makes it difficult to ascertain the role of these proteins. Metabolomics approaches are useful in characterizing proteins that regulate or bind metabolites. Here, we provide examples of the development and use of metabolomics approaches to elucidate protein-metabolite interactions. PMID- 22083211 TI - 20 years of DNA-encoded chemical libraries. AB - The identification of specific binding molecules is a central problem in chemistry, biology and medicine. Therefore, technologies, which facilitate ligand discovery, may substantially contribute to a better understanding of biological processes and to drug discovery. DNA-encoded chemical libraries represent a new inexpensive tool for the fast and efficient identification of ligands to target proteins of choice. Such libraries consist of collections of organic molecules, covalently linked to a unique DNA tag serving as an amplifiable identification bar code. DNA-encoding enables the in vitro selection of ligands by affinity capture at sub-picomolar concentrations on virtually any target protein of interest, in analogy to established selection methodologies like antibody phage display. Multiple strategies have been investigated by several academic and industrial laboratories for the construction of DNA-encoded chemical libraries comprising up to millions of DNA-encoded compounds. The implementation of next generation high-throughput sequencing enabled the rapid identification of binding molecules from DNA-encoded libraries of unprecedented size. This article reviews the development of DNA-encoded library technology and its evolution into a novel drug discovery tool, commenting on challenges, perspectives and opportunities for the different experimental approaches. PMID- 22083212 TI - Histopathology of surgically treated renal tumours in young adults: a developing country perspective. AB - BACKGROUND: There is no data on the histopathological characteristics of renal tumours in young adults in Pakistan. MATERIALS AND METHODS: We retrospectively analysed 133 young adults (age: 16 to <=40 years) who underwent nephrectomy for suspected renal cancer from 1994 till July 2010. The demographical and pathological parameters were determined from original surgical biopsy reports and case files, and analysed. RESULTS: The mean age of patients was 33.3 +/- 6.2 years. Overall, 121 (88.9%) renal tumours were malignant, and 15 (11%) benign. Among malignant tumours, renal cell carcinoma (RCC) was predominant (100/121; 82.6%). The subtypes of RCC included: clear cell RCC, 84 (84%); papillary RCC, 11 (11%), chromophobe RCC, 3 (3%) and sarcomatoid RCC, 2 (2%). Other malignant tumours included: transitional cell carcinoma (9/121; 7.4%), primitive neuroectodermal tumour (5/121; 4.1%), synovial sarcoma (2/121; 1.6%), Non Hodgkin's lymphoma (2/121; 1.6%), leiomyosarcoma (1/121; 0.8%), malignant fibrous histiocytoma (1/121; 0.8%) and squamous cell carcinoma (1/121; 0.8%). Among benign tumours, there were 11 cases of angiomyolipoma (11/15; 73.3%), three cases of oncocytoma (3/15; 20%) and one case of schwannoma (1/15; 6.6%). Almost two third (62.7%) patients had stage I/II tumours, 22 (18.1%) stage III and 23 (19%) stage IV disease at the time of surgery. CONCLUSION: A wide variety of renal tumours is documented in young adults with large size of the tumours and late presentation in our population. PMID- 22083215 TI - Ownership. PMID- 22083213 TI - Aberrant expression of intelectin-1 in gastric cancer: its relationship with clinicopathological features and prognosis. AB - PURPOSES: Human intelectin-1 (ITLN-1) is a novel identified galactose-binding lectin that is expressed in the colonic goblet cells. Since gastric adenocarcinomas can arise through a process of intestinalization, we speculate that ITLN-1 may be aberrantly expressed in gastric cancer. This study was undertaken to examine the ITLN-1 expression in gastric cancer and correlate it with clinical outcomes. METHODS: One hundred and ninety-six gastric cancer patients were evaluated for the ITLN-1 expression by immunohistochemistry. The ITLN-1 transcripts were measured by real-time quantitative PCR. RESULTS: ITLN-1 expression was absent in normal gastric mucosa, whereas areas of intestinal metaplasia revealed ITLN-1 immunoreactivity. One hundred and forty-two gastric cancer patients (72.4%) were positive for ITLN-1 expression. In a subtotal of 20 patients, ITLN-1 transcripts were significantly enhanced in gastric cancer tissues than in normal gastric mucosa (P < 0.001). The expression rate of ITLN-1 was higher in intestinal-type carcinomas than in diffuse-type carcinomas (P = 0.003). ITLN-1 positivity in gastric cancer was positively correlated with tumor differentiation (P = 0.001) and CDX2 expression (P < 0.001), and inversely correlated with depth of invasion (P = 0.007), lymph node metastasis (P = 0.001), distant metastasis (P = 0.014), clinical stage (P = 0.006), Ki-67 expression (P = 0.001), and heparanase expression (P < 0.001), without correlation with age, gender, tumor location, or tumor size. In univariate and multivariate analyses, ITLN-1 was an independent prognostic factor for longer survival of gastric cancer patients (P = 0.001). CONCLUSION: The aberrant ITLN-1 expression in gastric cancer is correlated with clinicopathological features and may be a useful prognostic factor for predicting the outcomes of gastric cancer patients. PMID- 22083214 TI - Noninvasive studies of central aortic pressure. AB - Our purpose is to review noninvasive methods for measuring central arterial pressure. Indices of central arterial pressure measured from central aortic and peripheral arterial waveforms have shown value in predicting cardiovascular events and death, as well as in guiding therapeutic management. This article reviews noninvasive techniques of measuring central arterial pressure that have been validated against intra-arterial pressure. This paper explains methods to derive central (aortic and carotid) pressure from radial and brachial sites. It focuses on specific issues of brachial calibration applied to carotid pressure waveforms, which were regarded as a surrogate of aortic pressures used in three major studies (Framingham, Asklepios, and Australian National Blood Pressure 2 studies). We explain why radial-based methods are superior to carotid-based methods for estimating central pressure. Physiological principles of pressure measurement need be satisfied to ensure accurate recording. PMID- 22083216 TI - Effect of the interaction between food state and the action of estrogen on oxytocinergic system activity. AB - Increased plasma osmolality by food intake evokes augmentation of plasma oxytocin (OT). Ovarian steroids may also influence the balance of body fluids by acting on OT neurones. Our aim was to determine if estrogen influences the activity of OT neurones in paraventricular nucleus (PVN) and supraoptic nucleus (SON) under different osmotic situations. Ovariectomized rats (OVX) were treated with either estradiol (E(2)) or vehicle and were divided into three groups: group I was fed ad libitum, group II underwent 48 h of fasting, and group III was refed after 48 h of fasting. On the day of the experiment, blood samples were collected to determine the plasma osmolality and OT. The animals were subsequently perfused, and OT/FOS immunofluorescence analysis was conducted on neurones in the PVN and the SON. When compared to animals which were fasted or fed ad libitum, the plasma osmolality of refed animals was higher, regardless of whether they were treated with vehicle or E(2). We observed neural activation of OT cells in vehicle- or E(2)-treated OVX rats refed after 48 h of fasting, but not in animals fed ad libitum or in animals that only underwent 48 h of fasting. Finally, the percentage of neurones that co-expressed OT and FOS was lower in both the PVN and the SON of animals treated with E(2) and refed, when compared to vehicle-treated animals. These results suggest that E(2) may have an inhibitory effect on OT neurones and may modulate the secretion of OT in response to the increase of osmolality induced by refeeding. PMID- 22083217 TI - Urocortin is a novel regulator of osteoclast differentiation and function through inhibition of a canonical transient receptor potential 1-like cation channel. AB - This study investigated the role of urocortin (UCN), a member of the corticotrophin-releasing factor (CRF) family of peptides, in osteoclast maturation and function. We found that 10(-7) M UCN significantly (P<0.05) suppressed osteoclast differentiation from bone marrow precursor cells in culture and reduced the expression of several osteoclastic markers. Furthermore, UCN potently suppressed osteoclast bone resorption, by significantly inhibiting both the plan area of bone resorbed by osteoclasts and actin ring formation within osteoclasts at 10(-9) M (P<0.05), with complete inhibition at 10(-7) M (P<0.001). UCN also inhibited osteoclast motility (10(-7) M) but had no effect on osteoclast survival. Osteoclasts expressed mRNA encoding both UCN and the CRF receptor 2beta subtype. Pre-osteoclasts however, expressed CRF receptor 2beta alone. Unstimulated osteoclasts contained constitutively active cation channel currents with a unitary conductance of 3-4 pS, which were inhibited by over 70% with UCN (10(-7) M). Compounds that regulate calcium signalling and energy status of the cell, both crucial for osteoclast activity were investigated. The non-selective cation channel blockers, lanthanum (La(3)(+)) and gadolinium (Gd(3)(+)), inhibited actin ring formation in osteoclasts, whereas modulators of voltage dependent Ca(2)(+) channels and K(ATP) channels had no effect. These findings show for the first time that UCN is a novel anti-resorptive molecule that acts through a direct effect on osteoclasts and their precursor cells. PMID- 22083218 TI - Connective tissue diseases: Unpicking Dupruyten disease etiology-is Wnt the way? PMID- 22083219 TI - Perioperative care for patients with rheumatic diseases. AB - The perioperative care of patients with rheumatic diseases is hampered by a lack of evidence-based recommendations. Rheumatologists are called upon to 'clear' their patients for surgery, yet the evidence upon which to base decisions is fractionated and inconsistent. We have systematically reviewed the current literature and developed suggestions for three key areas that require particular deliberations in patients with rheumatic diseases scheduled for surgery: the management of cardiovascular risk, use of immunosuppressive drugs, and states of altered coagulation. For patients with rheumatic diseases associated with increased cardiovascular risk, such as rheumatoid arthritis and systemic lupus erythematosus, we suggest following the American College of Cardiology-American Heart Association guidelines using the underlying disease as a risk modifier. Most evidence suggests a neutral effect of conventional DMARDs in the perioperative period, with no need to discontinue them prior to surgery. Conversely, we suggest minimizing perioperative steroid use and unnecessary 'steroid preps'. The potential benefits of discontinuing biologic drugs in the perioperative setting needs to be carefully balanced with the risks associated with a disease flare. We discuss the American College of Chest Physicians guidelines, which classify individuals with antiphospholipid antibody syndrome as high-risk patients for perioperative thrombosis who are likely to require bridging therapy in most perioperative settings. PMID- 22083221 TI - Screening: Assessing bone structure in the prediction of osteoporotic fractures. PMID- 22083220 TI - Cardiovascular safety of biologic therapies for the treatment of RA. AB - Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies. PMID- 22083222 TI - Experimental arthritis: EBV induces arthritis in mice. PMID- 22083223 TI - Validation of the Dutch version of the VascuQol questionnaire and the Amsterdam Linear Disability Score in patients with intermittent claudication. AB - PURPOSE: To assess the reliability and validity of the Dutch version of the vascular quality of life questionnaire (VascuQol) and the AMC Linear Disability Score (ALDS) in patients with stable intermittent claudication (IC). METHODS: During a 5-month period we performed a prospective study in which we included every patient with stable IC, who visited our vascular surgery outpatient clinic and consented to participate. Forty consecutive patients filled in the Dutch VascuQol, the ALDS, and Short Form-36 (SF-36). Twenty patients filled in the same questionnaires after 4 weeks. Internal reliability consistencies were expressed as Cronbach's alpha. Test-retest reliability was expressed as intraclass correlation coefficients (ICC). Construct validity was expressed as Spearman rho correlations between SF-36 and relevant domains of Dutch VascuQol and the ALDS. RESULTS: Internal reliability consistencies were, respectively, good and excellent for the total scores of VascuQol, SF-36, and ALDS (Cronbach's alpha. 0.87, 0.89, and 0.92). Test-retest reliability was excellent for the total VascuQol scores [ICC 0.91 (95% CI, 0.78-0.96)], and for the ALDS [ICC 0.90 (95% CI, 0.76-0.96)]. Spearman correlations between VascuQol, ALDS, and SF-36 domains varied from r = 0.34-0.79. CONCLUSION: The Dutch VascuQol is a valid and reliable questionnaire for assessment of Qol in patients with IC. This study confirms the good clinimetric properties of the ALDS for assessing disability in patients with IC. PMID- 22083224 TI - Solar hydrogen production with semiconductor metal oxides: new directions in experiment and theory. AB - An overview of a collaborative experimental and theoretical effort toward efficient hydrogen production via photoelectrochemical splitting of water into di hydrogen and di-oxygen is presented here. We present state-of-the-art experimental studies using hematite and TiO(2) functionalized with gold nanoparticles as photoanode materials, and theoretical studies on electro and photo-catalysis of water on a range of metal oxide semiconductor materials, including recently developed implementation of self-interaction corrected energy functionals. PMID- 22083226 TI - A novel BF2-chelated azadipyrromethene-fullerene dyad: synthesis, electrochemistry and photodynamics. AB - The synthesis, structure, electrochemistry and photodynamics of a BF(2)-chelated azadipyrromethene-fullerene dyad are reported in comparison with BF(2)-chelated azadipyrromethene without fullerene. The attachment of fullerene resulted in efficient generation of the triplet excited state of the azadipyrromethene via photoinduced electron transfer. PMID- 22083225 TI - Cooperation, conflict, and the evolution of queen pheromones. AB - While chemical communication regulates individual behavior in a wide variety of species, these communication systems are most elaborated in insect societies. In these complex systems, pheromones produced by the reproductive individuals (queens) are critical in establishing and maintaining dominant reproductive status over hundreds to thousands of workers. The proximate and ultimate mechanisms by which these intricate pheromone communication systems evolved are largely unknown, though there has been much debate over whether queen pheromones function as a control mechanism or as an honest signal facilitating cooperation. Here, we summarize results from recent studies in honey bees, bumble bees, wasps, ants and termites. We further discuss evolutionary mechanisms by which queen pheromone communication systems may have evolved. Overall, these studies suggest that queen-worker pheromone communication is a multi-component, labile dialog between the castes, rather than a simple, fixed signal-response system. We also discuss future approaches that can shed light on the proximate and ultimate mechanisms that underlie these complex systems by focusing on the development of increasingly sophisticated genomic tools and their potential applications to examine the molecular mechanisms that regulate pheromone production and perception. PMID- 22083227 TI - [Pertrochanteric fractures. What impact do surgical timing and implant choice have on the outcome?]. AB - Pertrochanteric fractures are grouped together with femoral neck fractures to represent the most frequent femur fractures in the region of the hip joint and usually occur in elderly people with preexisting conditions. Analysis of the data from the 2004/2005 quality assurance program of North Rhine-Westphalia shows, just as is the case for medial femoral neck fractures, that not only does delayed management increase risk-adjusted general and surgical complications but also mortality. PMID- 22083228 TI - [Suicide in old age: the underestimated risk. An analysis of 1,894 patients in the Trauma Registry of the German Trauma Society]. AB - BACKGROUND: In Germany, the number of suicides and suicide attempts (n = 9,616) exceeds the number of traffic deaths (n = 4,152) by far. It is unknown how many suicide attempts are treated in trauma centres. Due to a lack of registered suicide attempts in Germany, no data exist about injury patterns, mortality or duration of treatment. MATERIALS AND METHODS: We prospectively analysed data collected on emergency room patients from the Trauma Registry of the German Trauma Society (TR-DGU) between 1993 and 2009. All patients with an Injury Severity Score (ISS) >= 9, age >= 18 years and a documented suicide attempt were included in the study. The main target points were epidemiological data, cause of injury and injury patterns, ISS, gender distribution, mortality, duration of treatment and patients' psychiatric medical history. RESULTS: Of 42,248 patients of the TR-DGU, 1,894 were included in the study; 274 patients were >= 65 years old. The most common method was jumping from a height among the group of female patients, whereas the use of firearms predominated in the male group. The average ISS was 31 points in all patient groups. The mortality was highest in patients aged >= 65 years. Psychiatric disorders were found predominantly in women. CONCLUSION: Of all severely injured patients in trauma centres, 5% suffered their injuries as a consequence of a suicidal attempt. In women who survived initially, jumping from a height was the most frequently chosen method. In elderly men the use of firearms dominated. The significant increase of mortality in elderly patients, preexisting depressive conditions and the expected increase in the number of these patients as a consequence of the changed age pyramid should lead to more intensive recognition and treatment of this disease and possibly improved suicide prevention. PMID- 22083230 TI - Case report and review of the literature: secretory breast cancer in a 13-year old boy--10 years of follow up. AB - Carcinoma of the breast is very rare in childhood, accounting for less than 1% of all childhood malignancies and is especially rare in boys. Delay in diagnosis and treatment in children with breast cancer may occur because surgeons are very reluctant to perform biopsies on the developing breast, since these can cause future deformity. We report a case of male secretory breast carcinoma in a 13 year-old boy. Radical mastectomy was performed followed by chemotherapy. The patient is free of disease after 10 years. Secretory breast carcinoma (SBC) is the commonest type of breast carcinoma in children. In this article, we discuss the diagnosis and treatment options for breast cancer among children as well as features of SBC, based on a literature review. PMID- 22083229 TI - A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer. AB - Heat shock protein 90 (Hsp90) is an attractive target for breast cancer treatment, as it is required for the proper folding and stabilization of several proteins known to be involved in breast cancer growth and development. These proteins include the epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), progesterone receptor (PR), and src. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is an intravenous Hsp90 inhibitor in development for breast cancer treatment. We conducted a phase II study of 17-AAG 220 mg/m(2) on days 1, 4, 8, and 11 every 21 days in patients with metastatic and locally advanced breast cancer. Since we expected the molecular effects of Hsp90 inhibition to extend beyond just ER, PR, and HER2 down regulation and to impact a variety of other cellular proteins, patients were not selected based on ER, PR, or HER2 status. Eleven patients, including 6 patients with triple negative breast cancer, were enrolled and treated. There were no responses and 3 patients had stable disease as their best response. Five patients developed grade 3/4 toxicities, which were primarily hepatic and pulmonary. Based on these results, we do not recommend further study of 17-AAG at this dosing schedule or in unselected breast cancer patients. PMID- 22083231 TI - Breast epithelial cell proliferation is markedly increased with short-term high levels of endogenous estrogen secondary to controlled ovarian hyperstimulation. AB - Oocyte donors have high serum estradiol (E2) levels similar to the serum levels seen in the first trimester of pregnancy. We report in this article our studies comparing cell proliferation, Ki67 (MIB1), and estrogen and progesterone receptor levels (ERalpha, PRA, and PRB) in the breast terminal duct lobular units of oocyte donors, women in early pregnancy, and in normally cycling women. Breast tissue and blood samples were obtained from 10 oocyte donors, and 30 pregnant women at 5-18 weeks of gestation. Breast tissue samples were also obtained from 26 normally cycling women. In the oocyte donors: peak E2 (mean ~15,300 pmol/l) was reached on the day before oocyte (and tissue) donation; peak progesterone (P4; mean 36.3 nmol/l) was reached on the day of donation; Ki67 was positively associated with level of E2, and the mean Ki67 was 7.0% significantly greater than the mean 1.8% of cycling women. In the pregnant women: mean E2 rose from ~2,000 pmol/l at 5 weeks of gestation to ~27,000 pmol/l at 18 weeks; mean P4 did not change from ~40 nmol/l until around gestational week 11 when it increased to ~80 nmol/l; mean Ki67 was 15.4% and did not vary with gestational age or E2. Oocyte donors have greatly increased levels of E2 and of breast-cell proliferation, both comparable in the majority of donors to the levels seen in the first trimester of pregnancy. Whether their short durations of greatly increased E2 levels are associated with any long-term beneficial effects on the breast, as occurring in rodent models, is not known. PMID- 22083232 TI - Topoisomerase 2A gene amplification in breast cancer. Critical evaluation of different FISH probes. AB - The HER2 amplicon on chromosome 17q is variable in size and occasionally includes Topoisomerase 2A (TOP2A) at 17q21-22. It has been suggested that TOP2 co amplification, not HER2 amplification on chromosome 17q11.2-12, is a useful predictive marker of response to anthracycline-based chemotherapy in breast cancer patients. Given the significant toxicities of anthracyclines, the detection methods of TOP2A gene amplifications have to be standardized. We determined TOP2A gene alterations using two different fluorescence in situ hybridization (FISH) DNA probes. HER2 amplifications were identified with the PathVysion probe. TOP2A status of 42 HER2 amplified breast cancers was tested by FISH with PathVysion covering 160 kb and DAKO pharm DX covering 228 kb of the TOP2A amplicon. TOP2A protein expression was tested by immunohistochemistry. Multiplex-ligation dependent probe amplification (MLPA) was performed retrospectively in cases showing discrepancies. TOP2A was amplified in 15 of 42 cases (35%) with DAKO pharm DX and in 11 of 42 cases (26%) with PathVysion. In all four discrepant cases, MLPA showed no TOP2A amplification, but instead amplification of an upstream region including HER2. TOP2A was deleted in the same seven of 42 carcinomas (17%) with both probes. TOP2A protein expression was detected in all 42 tumours (100%) with high intratumoral heterogeneity. TOP2A amplification rate depends on the length of the hybridized probes for the TOP2A locus. Because TOP2A, not HER2, is a target of anthracyclines, non-overlapping DNA probes should be used to evaluate any associations between such alterations and response to anthracycline-based chemotherapy. PMID- 22083234 TI - Mapping of locus for autosomal dominant retinitis pigmentosa on chromosome 6q23. AB - Retinitis pigmentosa (RP) is a genetically heterogeneous group of retinal degenerative disorders resulting in severe visual loss and blindness that have remained incurable till date. We report the mapping of the disease locus in a 3 generation family of Indian origin with autosomal dominant RP (ADRP). Diagnosis of RP and recruitment was made after a complete clinical evaluation of all members. Manifestations of the disease included night blindness with blurred central vision in some cases, loss of peripheral vision, and diffuse degeneration of the retinal pigment epithelium. Linkage analysis using microsatellite markers was carried out on 34 members (14 affected). After testing for linkage to known retinal dystrophy loci as well as a subsequent genome-wide analysis, we detected linkage to markers on chromosome 6q23: D6S262 at 130 cM, D6S457 (130 cM) and D6S1656 (131 cM) gave significant 2-point LOD scores of 3.0-3.8. Multipoint LOD scores of >=3.0 were obtained for markers between 121 and 130 cM. Haplotype analysis with several markers in the same region on chromosome 6 shows a disease cosegregating region of about 25 Mb between 109 and 135 Mb. There are no known RP genes in this interval, which contains >100 genes. This study provides evidence for a novel ADRP locus on chromosome 6q23. PMID- 22083233 TI - Solid-phase submonomer synthesis of peptoid polymers and their self-assembly into highly-ordered nanosheets. AB - Peptoids are a novel class of biomimetic, non-natural, sequence-specific heteropolymers that resist proteolysis, exhibit potent biological activity, and fold into higher order nanostructures. Structurally similar to peptides, peptoids are poly N-substituted glycines, where the side chains are attached to the nitrogen rather than the alpha-carbon. Their ease of synthesis and structural diversity allows testing of basic design principles to drive de novo design and engineering of new biologically-active and nanostructured materials. Here, a simple manual peptoid synthesis protocol is presented that allows the synthesis of long chain polypeptoids (up to 50mers) in excellent yields. Only basic equipment, simple techniques (e.g. liquid transfer, filtration), and commercially available reagents are required, making peptoids an accessible addition to many researchers' toolkits. The peptoid backbone is grown one monomer at a time via the submonomer method which consists of a two-step monomer addition cycle: acylation and displacement. First, bromoacetic acid activated in situ with N,N' diisopropylcarbodiimide acylates a resin-bound secondary amine. Second, nucleophilic displacement of the bromide by a primary amine follows to introduce the side chain. The two-step cycle is iterated until the desired chain length is reached. The coupling efficiency of this two-step cycle routinely exceeds 98% and enables the synthesis of peptoids as long as 50 residues. Highly tunable, precise and chemically diverse sequences are achievable with the submonomer method as hundreds of readily available primary amines can be directly incorporated. Peptoids are emerging as a versatile biomimetic material for nanobioscience research because of their synthetic flexibility, robustness, and ordering at the atomic level. The folding of a single-chain, amphiphilic, information-rich polypeptoid into a highly-ordered nanosheet was recently demonstrated. This peptoid is a 36-mer that consists of only three different commercially available monomers: hydrophobic, cationic and anionic. The hydrophobic phenylethyl side chains are buried in the nanosheet core whereas the ionic amine and carboxyl side chains align on the hydrophilic faces. The peptoid nanosheets serve as a potential platform for membrane mimetics, protein mimetics, device fabrication, and sensors. Methods for peptoid synthesis, sheet formation, and microscopy imaging are described and provide a simple method to enable future peptoid nanosheet designs. PMID- 22083235 TI - Purification of a lectin from Arisaema erubescens (Wall.) Schott and its pro inflammatory effects. AB - The monocot lectin from the tubers of Arisaema erubescens (Wall.) Schott has been purified by consecutive hydrophobic chromatography and ion exchange chromatography methods. The molecular weight of this A. erubescens lectin (AEL) was determined to be about 12 kDa by high performance liquid chromatography (HPLC) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) methods. AEL could agglutinate rabbit erythrocytes. The haemagglutination activity of AEL was only inhibited by asialofetuin, while monosaccharide did not react. Rat paw edema and neutrophil migration models were used to investigate the pro-inflammatory activity of AEL. AEL (100 and 200 MUg/paw) could induce significant rat paw edema. In addition, AEL (100, 200 and 300 MUg/mL/cavity) could induce significant and dose-dependent neutrophil migration in the rat peritoneal cavities. Besides, AEL at doses ranging from 100 to 300 MUg/mL/cavity could significantly increase the concentration of nitric oxide (NO), prostaglandin E(2 )(PGE(2)) and tumor necrosis factor alpha (TNF-alpha) in peritoneal fluid. As compared with control animals, 75% depletion in the number of resident cells following peritoneal lavage did not reduce the AEL-induced neutrophil migration. However, pre-treatment with 3% thioglycollate which increased the peritoneal macrophage population by 201%, enhanced the neutrophil migration induced by AEL (200 MUg/mL/cavity) (p < 0.05). Reduction of peritoneal mast cell population by chronic treatment of rat peritoneal cavities with compound 48/80 (N-methyl-p-methoxyphenethylamine with formaldehyde) did not modify AEL-induced neutrophil migration. The results provided the basis for identifying the toxic components of A. erubescens and AEL could be a new useful tool for pro-inflammatory research. PMID- 22083236 TI - Synthesis of endohedral metallofullerene glycoconjugates by carbene addition. AB - Endohedral metallofullerene glycoconjugates were synthesized under mild conditions by carbene addition using appropriate glycosylidene-derived diazirine with La(2)@I(h)-C(80). NMR spectroscopic studies revealed that the glycoconjugate consists of two diastereomers of [6,6]-open mono-adducts. The electronic properties were characterized using Vis/NIR absorption spectroscopy and electrochemical measurements. This study demonstrates that glycosylidene carbene is useful to incorporate carbohydrate moieties onto endohedral metallofullerene surfaces. PMID- 22083239 TI - Metastasis of a ductal breast carcinoma to the buccal mucosa of the mandible with tooth involvement. AB - BACKGROUND: We present a metastatic tumour from the breast to the gingiva, with the rare finding of tooth invasion. Metastatic tumours to the oral region are uncommon. The breast is the most common primary site for metastatic tumours to the jawbones in women, with the mandible being most often affected. CASE REPORT: We report the case of a 52-year-old Caucasian woman who presented with a swelling of the buccal mucosa in the molar region of the left mandible. Biopsy revealed a metastatic lesion, with involvement of the two adjacent molars. Immunohistochemical analysis ruled out other malignancies and confirmed the diagnosis of a ductal breast carcinoma origin. DISCUSSION: Management in such cases should be in the context of the treatment of a metastatic disease that could prolong survival and improve quality of life, but is not curative. Tooth invasion has been described since 1910 for different primary malignancies with distant metastases to the oral cavity. This report seems to describe the second case in the literature of a metastatic breast carcinoma to the mandible with tooth invasion. Management in such cases should be in the context of the treatment of a metastatic disease that could prolong survival and improve quality of life, but is not curative. PMID- 22083238 TI - Novel insights into the pathomechanisms of skeletal muscle channelopathies. AB - The nondystrophic myotonias and primary periodic paralyses are an important group of genetic muscle diseases characterized by dysfunction of ion channels that regulate membrane excitability. Clinical manifestations vary and include myotonia, hyperkalemic and hypokalemic periodic paralysis, progressive myopathy, and cardiac arrhythmias. The severity of myotonia ranges from severe neonatal presentation causing respiratory compromise through to mild later-onset disease. It remains unclear why the frequency of attacks of paralysis varies greatly or why many patients develop a severe permanent fixed myopathy. Recent detailed characterizations of human genetic mutations in voltage-gated muscle sodium (gene: SCN4A), chloride (gene: CLCN1), calcium (gene: CACNA1S), and inward rectifier potassium (genes: KCNJ2, KCNJ18) channels have resulted in new insights into disease mechanisms, clinical phenotypic variation, and therapeutic options. PMID- 22083240 TI - In vivo monitoring of organ-selective distribution of CdHgTe/SiO2 nanoparticles in mouse model. AB - CdHgTe/SiO(2) nanoparticles were prepared by SiO(2) capping on the surface of CdHgTe QDs. The characteristics, such as optical spectra, photostability, size and cell toxicity were investigated. The dynamic distribution of CdHgTe/SiO(2) nanoparticles was in vivo monitored by near infrared fluorescence imaging system. CdHgTe/SiO(2) nanoparticles acted as a novel fluorescence probe have a maximum fluorescence emission of 785 nm and high photo-stability. The hydrodynamic diameter of CdHgTe/SiO(2) nanoparticles could be adjusted to 122.3 nm. Compared to CdHgTe QDs, inhibitory effects of CdHgTe/SiO(2) nanoparticles on proliferation of HCT116 cells decreased to a certain extent. CdHgTe/SiO(2) nanoparticles had their specific dynamic distribution behavior, which provided new perspectives for bio-distribution of nanoparticles. PMID- 22083241 TI - Urinary incontinence: incontinence guidelines--is lack of adherence a form of ageism? PMID- 22083242 TI - Therapy: two birds, one stone: tadalafil is an effective treatment for men with both BPH-LUTS and ED. PMID- 22083243 TI - Prostate cancer: Scribble complex protein deficiency promotes prostate tumors in vivo. PMID- 22083244 TI - Kidney cancer: zero-ischemia partial nephrectomy--further evaluations are needed. PMID- 22083245 TI - Prostate cancer: Vitamin E and prostate cancer--what is the real risk? PMID- 22083246 TI - The evaluation of myomectomies performed during cesarean section in our clinic. AB - BACKGROUND: We evaluated the data of patients who had applied myomectomy during cesarean section operation in our clinic between April, 2008 and December, 2010. OBJECTIVE: I0 n this period, 3689 cesarean sections were done in our clinic, we analyzed their data retrospectively and determined 27 myomectomy cases during cesarean section operation. The age of the patients, the numbers of pregnancy, parities, the rates of abortus, indications of cesarean, pregnancy weeks, residential areas of myoms detected during the cesarean and their size, were recorded. Furthermore, pre-operative and post-operative hemoglobin (Hb) values, differences between hemoglobin values, whether there was bleeding or not, the need of blood transfusion if it occurred, the duration of operation and hospitaization and the pathological diagnoses of myomectomy materials, were examined. MATERIALS AND METHODS: Retrospective study of myomectomies. RESULTS: The mean age of patients was 29.6+/-5.9 (19-42) and mean gestational age was 39.2+/-1.0(37-42) weeks. The mean size of the fibroids was 5.94+/-6.29 cm(3) (0.96-26.50 cm3). Subserous myoms were the most frequently seen ones (24 of 27 patients=89%) with fundal, corporal localizations in most of the instances. T0 he pre-operative and post-operative values of Hb were 11.8+/-1.52 (8.6-10.5) and 10.3+/-2.6 (6.9-13.3) g/dl respectively and the difference was statistically significant (P<0.001). Blood transfusion was not necessary in any patient. The mean duration of the operation was found to be 40.7+/-13.9 (13-60) minutes. CONCLUSION: Myomectomies can be performed safely during cesarean section by experienced obstetricians and gynecologists, and myomectomy performed for fibroids in appropriate localizations does not increase post-operative bleeding or maternal morbidity or mortality. PMID- 22083247 TI - Coloring genetically modified soybean grains with anthocyanins by suppression of the proanthocyanidin genes ANR1 and ANR2. AB - Detection and quantification of the levels of adventitious presence of genetically modified (GM) soybeans in non-GM grain shipments currently requires sophisticated tests that can have issues with their reproducibility. We show here that pigment biosynthesis in the soybean seed coat can be manipulated to provide a distinct color that would enable the simple visible detection of the GM soybean grain. We observed that a distinct red-brown grain color could be engineered by the simultaneous suppression of two proanthocyanidin (PA) genes, ANTHOCYANIDIN REDUCTASE1 (ANR1) and ANR2. Multiple reaction monitoring by liquid chromatography tandem mass spectrometry was used to quantify differentially accumulated seed coat metabolites, and revealed the redirection of metabolic flux into the anthocyanin pigment pathway and unexpectedly the flavonol-3-O-glucoside pathway. The upregulations of anthocyanin isogenes (DFR1 and GST26) and the anthocyanin/flavonol-3-O-glycosyltransferase (UGT78K2) were identified by quantitative RT-PCR to be endogenous feedback and feedforward responses to overaccumulation of upstream flavonoid intermediates resulting from ANR1 and ANR2 suppressions. These results suggested the transcription of flavonoid genes to be a key component of the mechanism responsible for the redirection of metabolite flux. This report identifies the suppression of PA genes to be a novel approach for engineering pigmentation in soybean grains. PMID- 22083249 TI - Quantum confinement controlled photocatalytic water splitting by suspended CdSe nanocrystals. AB - The photocatalytic hydrogen production of CdSe nanocrystals (1.75-4.81 nm) in the presence of aqueous sodium sulphite depends exponentially on the bandgap of the particles, confirming that the material's activity is controlled by the degree of quantum confinement. PMID- 22083250 TI - Bacterial diversity in the cecum of the world's largest living rodent (Hydrochoerus hydrochaeris). AB - The capybara (Hydrochoerus hydrochaeris) is the world's largest living rodent. Native to South America, this hindgut fermenter is herbivorous and coprophagous and uses its enlarged cecum to digest dietary plant material. The microbiota of specialized hindgut fermenters has remained largely unexplored. The aim of this work was to describe the composition of the bacterial community in the fermenting cecum of wild capybaras. The analysis of bacterial communities in the capybara cecum is a first step towards the functional characterization of microbial fermentation in this model of hindgut fermentation. We sampled cecal contents from five wild adult capybaras (three males and two females) in the Venezuelan plains. DNA from cecal contents was extracted, the 16S rDNA was amplified, and the amplicons were hybridized onto a DNA microarray (G2 PhyloChip). We found 933 bacterial operational taxonomic units (OTUs) from 182 families in 21 bacterial phyla in the capybara cecum. The core bacterial microbiota (present in at least four animals) was represented by 575 OTUs. About 86% of the cecal bacterial OTUs belong to only five phyla, namely, Firmicutes (322 OTUs), Proteobacteria (301 OTUs), Bacteroidetes (76 OTUs), Actinobacteria (69 OTUs), and Sphirochaetes (37 OTUs). The capybara harbors a diverse bacterial community that includes lineages involved in fiber degradation and nitrogen fixation in other herbivorous animals. PMID- 22083251 TI - New stem-sauropodomorph (Dinosauria, Saurischia) from the Triassic of Brazil. AB - Post-Triassic theropod, sauropodomorph, and ornithischian dinosaurs are readily recognized based on the set of traits that typically characterize each of these groups. On the contrary, most of the early members of those lineages lack such specializations, but share a range of generalized traits also seen in more basal dinosauromorphs. Here, we report on a new Late Triassic dinosaur from the Santa Maria Formation of Rio Grande do Sul, southern Brazil. The specimen comprises the disarticulated partial skeleton of a single individual, including most of the skull bones. Based on four phylogenetic analyses, the new dinosaur fits consistently on the sauropodomorph stem, but lacks several typical features of sauropodomorphs, showing dinosaur plesiomorphies together with some neotheropod traits. This is not an exception among basal dinosaurs, the early radiation of which is characterized by a mosaic pattern of character acquisition, resulting in the uncertain phylogenetic placement of various early members of the group. PMID- 22083252 TI - Seaweed intake and urinary sex hormone levels in preschool Japanese children. AB - PURPOSE: We investigated whether seaweed intake is associated with sex steroid levels in young Japanese children. METHODS: The design of the study was cross sectional and it was conducted in October-November 2006. Subjects were substantially healthy preschoolers, 230 boys and 198 girls, aged 3-6 years. Dietary data, including seaweed intake, were assessed using 3-day dietary records covering 2 consecutive weekdays and 1 weekend day. Urinary estrone, estradiol, testosterone, and 5-androstene-3beta,17alpha diol levels were measured by liquid chromatography-electrospray ionization tandem mass spectrometry. Urinary dehydroepiandrosterone level was measured with a radioimmunoassay. Steroid hormones were adjusted for urinary creatinine levels. RESULTS: Spearman's correlation coefficient between seaweed intake and estrone level was -0.144 (p = 0.030) in boys and -0.147 (p = 0.041) in girls after adjustments for age, BMI, and total energy intake. Seaweed intake was neither associated with estradiol, testosterone, 3beta,17alpha-AED nor with DHEA among boys and girls. CONCLUSIONS: The negative association between seaweed intake and estrone level suggests that dietary seaweed intake might affect estrogen metabolism in childhood. PMID- 22083253 TI - Neurofibromatosis 2011: a report of the Children's Tumor Foundation annual meeting. AB - The 2011 annual meeting of the Children's Tumor Foundation, the annual gathering of the neurofibromatosis (NF) research and clinical communities, was attended by 330 participants who discussed integration of new signaling pathways into NF research, the appreciation for NF mutations in sporadic cancers, and an expanding pre-clinical and clinical agenda. NF1, NF2, and schwannomatosis collectively affect approximately 100,000 persons in US, and result from mutations in different genes. Benign tumors of NF1 (neurofibroma and optic pathway glioma) and NF2 (schwannoma, ependymoma, and meningioma) and schwannomatosis (schwannoma) can cause significant morbidity, and there are no proven drug treatments for any form of NF. Each disorder is associated with additional manifestations causing morbidity. The research presentations described in this review covered basic science, preclinical testing, and results from clinical trials, and demonstrate the remarkable strides being taken toward understanding of and progress toward treatments for these disorders based on the close interaction among scientists and clinicians. PMID- 22083254 TI - Clinical and neuropathologic heterogeneity of c9FTD/ALS associated with hexanucleotide repeat expansion in C9ORF72. AB - Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are part of a disease spectrum associated with TDP-43 pathology. Strong evidence supporting this is the existence of kindreds with family members affected by FTD, ALS or mixed features of FTD and ALS, referred to as FTD-MND. Some of these families have linkage to chromosome 9, with hexanucleotide expansion mutation in a noncoding region of C9ORF72. Discovery of the mutation defines c9FTD/ALS. Prior to discovery of mutations in C9ORF72, it was assumed that TDP-43 pathology in c9FTD/ALS was uniform. In this study, we examined the neuropathology and clinical features of 20 cases of c9FTD/ALS from a brain bank for neurodegenerative disorders. Included are six patients clinically diagnosed with ALS, eight FTD, one FTD-MND and four Alzheimer-type dementia. Clinical information was unavailable for one patient. Pathologically, the cases all had TDP-43 pathology, but there were three major pathologic groups: ALS, FTLD-MND and FTLD-TDP. The ALS cases were morphologically similar to typical sporadic ALS with almost no extramotor TDP-43 pathology; all had oligodendroglial cytoplasmic inclusions. The FTLD-MND showed predominantly Mackenzie Type 3 TDP-43 pathology, and all had ALS like pathology in motor neurons, but more extensive extramotor pathology, with oligodendroglial cytoplasmic inclusions and infrequent hippocampal sclerosis. The FTLD-TDP cases had several features similar to FTLD-TDP due to mutations in the gene for progranulin, including Mackenzie Type 1 TDP-43 pathology with neuronal intranuclear inclusions and hippocampal sclerosis. FTLD-TDP patients were older and some were thought to have Alzheimer-type dementia. In addition to the FTD and ALS clinical presentations, the present study shows that c9FTD/ALS can have other presentations, possibly related to age of onset and the presence of hippocampal sclerosis. Moreover, there is pathologic heterogeneity not only between ALS and FTLD, but also within the FTLD group. Further studies are needed to address the molecular mechanism of clinical and pathological heterogeneity of c9FTD/ALS due to mutations in C9ORF72. PMID- 22083256 TI - Weight change during and after Ramadan fasting. AB - BACKGROUND: During Ramadan, observant Muslims fast from sunrise to sunset for a month. Knowing whether Ramadan fasting affects body weight has implications for health advice to the Muslim community, for understanding the effects of skipping meals on body weight, and for general weight management advice. METHODS: We compared body weight before and after the Ramadan fast and 1 month later in observant Muslims attending a Mosque in East London, UK. RESULTS: In 202 participants who provided weight at the beginning and the end of Ramadan, there was a small weight decrease (-0.84 kg, 95% CI = -0.6 to -1, P < 0.0001), with 46% of participants losing >1 kg. Participants who fasted throughout Ramadan lost significantly more weight (1 kg) than those who occasionally broke fast (0.3 kg, P = 0.013). In 87 participants who provided weight at the beginning and end of Ramadan and also 1 month later, all the lost weight was regained (+0.1 kg, 95% CI = 0.2-0.5, P = 0.504 compared with baseline). CONCLUSIONS: Observers of Ramadan lose on average about a kilogram of weight over 4 weeks, and the lost weight is quickly regained. Current weight management treatments generally assume that skipping meals leads to weight gain and advise against it. The finding suggests that further research is needed on the justification of the 'do not skip meals' advice. PMID- 22083255 TI - An experimental rat model of sporadic Alzheimer's disease and rescue of cognitive impairment with a neurotrophic peptide. AB - Alzheimer's disease (AD) is multifactorial and, to date, no single cause of the sporadic form of this disease, which accounts for over 99% of the cases, has been established. In AD brain, protein phosphatase-2A (PP2A) activity is known to be compromised due to the cleavage and translocation of its potent endogenous inhibitor, I2PP2A, from the neuronal nucleus to the cytoplasm. Here, we show that adeno-associated virus vector-induced expression of the N-terminal I2NTF and C terminal I2CTF halves of I2PP2A , also called SET, in brain reproduced key features of AD in Wistar rats. The I2NTF-CTF rats showed a decrease in brain PP2A activity, abnormal hyperphosphorylation and aggregation of tau, a loss of neuronal plasticity and impairment in spatial reference and working memories. To test whether early pharmacologic intervention with a neurotrophic molecule could rescue neurodegeneration and behavioral deficits, 2.5-month-old I2NTF-CTF rats and control littermates were treated for 40 days with Peptide 6, an 11-mer peptide corresponding to an active region of the ciliary neurotrophic factor. Peripheral administration of Peptide 6 rescued neurodegeneration and cognitive deficit in I2NTF-CTF animals by increasing dentate gyrus neurogenesis and mRNA level of brain derived neurotrophic factor. Moreover, Peptide 6-treated I2NTF-CTF rats showed a significant increase in dendritic and synaptic density as reflected by increased expression of synapsin I, synaptophysin and MAP2, especially in the pyramidal neurons of CA1 and CA3 of the hippocampus. PMID- 22083257 TI - Vemurafenib and BRAF inhibition: a new class of treatment for metastatic melanoma. AB - The U.S. Food and Drug Administration recently approved vemurafenib for the treatment of BRAF valine in exon 15, at codon 600 (V600E) mutant metastatic melanoma. Vemurafenib is a competitive small-molecule serine-threonine kinase inhibitor that functions by binding to the ATP-binding domain of mutant BRAF. Compared with dacarbazine chemotherapy, vemurafenib significantly improved the 6 month overall survival of patients from 64% to 84% and exhibited a response rate of approximately 50%. Median progression-free survival was also significantly improved with vemurafenib as compared with dacarbazine (5.3 versus 1.6 months, respectively), and this was consistent among groups analyzed, including age, sex, geography, Eastern Cooperative Oncology Group status, disease stage, and serum lactate dehydrogenase. The success of targeting melanoma genomics has created a paradigm shift for future drug development. Currently, the elucidation of resistant mechanisms to vemurafenib therapy remains an important area of active investigation that will shape rational drug treatments for melanoma. The development of vemurafenib, the role of BRAF targeting, and the changing landscape of treatment for melanoma provide a new foundation for clinical investigation. PMID- 22083259 TI - Electrochemical synthesis of CdS/ZnO nanotube arrays with excellent photoelectrochemical properties. AB - A facile electrochemical method was developed to synthesize CdS/ZnO nanotube arrays. Implemented as the photoanode in a photoelectrochemical cell, the CdS/ZnO nanotube arrays exhibited a photocurrent as high as 10.64 mA cm(-2). PMID- 22083260 TI - Differentiation of mesenchymal stem cells in heparin-containing hydrogels via coculture with osteoblasts. AB - The therapeutic potency of delivered mesenchymal stem cells (MSCs) in tissue engineering applications may be improved by priming cells toward a differentiated state via coculture with native, differentiated cells prior to implantation; however, there is a lack of understanding in what may be the most efficacious method. The objective of this study was to investigate the role of negatively charged heparin in priming hydrogel-encapsulated MSCs toward the osteoblastic lineage during coculture with a monolayer of osteoblasts in the absence of dexamethasone. MSCs encapsulated with higher amounts of heparin and cocultured with osteoblasts exhibited an over 36-fold increase in alkaline phosphatase activity and 13-fold increase in calcium accumulation by day 21, compared to MSCs cocultured with MSCs at the same heparin content. Moreover, hydrogels with higher amounts of heparin and cocultured with osteoblasts exhibited enhanced mineralization on the edges, suggesting that heparin may be important in sequestering osteoblast-secreted soluble factors, particularly on the surfaces of hydrogels. The ability of heparin to selectively interact with soluble positively charged proteins from the surroundings was confirmed through protein labeling and microscopy. These results suggest that heparin-containing hydrogels as part of a coculture system can be utilized as a versatile platform to study and enhance priming of MSCs toward various cell types for a wide variety of regenerative medicine-based therapies. PMID- 22083261 TI - Using reverse genetics to manipulate the NSs gene of the Rift Valley fever virus MP-12 strain to improve vaccine safety and efficacy. AB - Rift Valley fever virus (RVFV), which causes hemorrhagic fever, neurological disorders or blindness in humans, and a high rate abortion and fetal malformation in ruminants, has been classified as a HHS/USDA overlap select agent and a risk group 3 pathogen. It belongs to the genus Phlebovirus in the family Bunyaviridae and is one of the most virulent members of this family. Several reverse genetics systems for the RVFV MP-12 vaccine strain as well as wild-type RVFV strains, including ZH548 and ZH501, have been developed since 2006. The MP-12 strain (which is a risk group 2 pathogen and a non-select agent) is highly attenuated by several mutations in its M- and L-segments, but still carries virulent S-segment RNA, which encodes a functional virulence factor, NSs. The rMP12-C13type (C13type) carrying 69% in-frame deletion of NSs ORF lacks all the known NSs functions, while it replicates as efficient as does MP-12 in VeroE6 cells lacking type-I IFN. NSs induces a shut-off of host transcription including interferon (IFN)-beta mRNA and promotes degradation of double-stranded RNA-dependent protein kinase (PKR) at the post-translational level. IFN-beta is transcriptionally upregulated by interferon regulatory factor 3 (IRF-3), NF-kB and activator protein-1 (AP-1), and the binding of IFN-beta to IFN-alpha/beta receptor (IFNAR) stimulates the transcription of IFN-alpha genes or other interferon stimulated genes (ISGs), which induces host antiviral activities, whereas host transcription suppression including IFN-beta gene by NSs prevents the gene upregulations of those ISGs in response to viral replication although IRF-3, NF-kB and activator protein-1 (AP-1) can be activated by RVFV7. Thus, NSs is an excellent target to further attenuate MP-12, and to enhance host innate immune responses by abolishing the IFN-beta suppression function. Here, we describe a protocol for generating a recombinant MP-12 encoding mutated NSs, and provide an example of a screening method to identify NSs mutants lacking the function to suppress IFN beta mRNA synthesis. In addition to its essential role in innate immunity, type-I IFN is important for the maturation of dendritic cells and the induction of an adaptive immune response. Thus, NSs mutants inducing type-I IFN are further attenuated, but at the same time are more efficient at stimulating host immune responses than wild-type MP-12, which makes them ideal candidates for vaccination approaches. PMID- 22083263 TI - Stimulating visual exploration of the neglected space in the early stage of stroke by hemifield eye-patching: a randomized controlled trial in patients with right brain damage. AB - BACKGROUND: It has been well established that the presence of neglect is a predictor of poor functional outcome after stroke. Most rehabilitation studies on neglect have been performed with at least two months post-stroke. However, a recent series of stroke management indications highlight the importance of early rehabilitation treatment and evidence regarding neglect rehabilitation in the early phase after stroke is needed. AIM: To evaluate the effectiveness of right half-field patches in treating neglect in patients during the early phase of stroke. DESIGN: Randomized controlled trial. SETTING: Acute care setting in an urban general hospital. POPULATION: Eighteen patients with left unilateral neglect recruited among 56 patients consecutively admitted with right hemispheric stroke. METHODS: The patients were evaluated at pre-treatment, post-treatment, and at a 7-day follow-up. The experimental group received right half-field patch treatment (n=10) for approximately 8 hours a day for 15 consecutive days. The control group received visual scanning training (n=8) for 40 minutes every weekday in a 15 day period. RESULTS: Both groups significantly improved their performance in all outcome measures. No difference in the amount of improvement between the two groups was found. CONCLUSION: Right half-field eye patching could be a promising technique for treating visual spatial neglect during the early stages of stroke. CLINICAL REHABILITATION IMPACT: The eye-patching technique may represent an easily applicable and inexpensive method for neglect rehabilitation in the early stage after stroke. PMID- 22083262 TI - Defining the differences between episodic migraine and chronic migraine. AB - Chronic migraine (CM) and episodic migraine (EM) are part of the spectrum of migraine disorders, but they are distinct clinical entities. Population-based studies have shown that those with CM demonstrate higher individual and societal burden because they are significantly more disabled than those with EM and have greater impaired quality of life both inside and outside the home. Proper diagnosis of both conditions requires clearly defined clinical criteria. Diagnosis enables the initiation of appropriate treatments and risk-factor modification, which ultimately improve functional status and quality of life for persons with migraine. Recognizing that both disorders are on the spectrum of migraine, this review serves as a guide to define the disease state of CM as distinct from EM in terms of clinical, epidemiological, sociodemographic, and comorbidity profiles. PMID- 22083264 TI - Persistent hiccup after surgical resection of a brainstem arteriovenous malformation: a case successfully treated with gabapentin during rehabilitation. Case report. AB - Persistent hiccup rarely occurs during rehabilitation, but its management can prove to be very difficult, particularly in presence of associated dysphagia, requiring longer hospitalization and higher risk of severe clinical complications. We present a case of persistent hiccup after surgical resection of a brainstem arteriovenous malformation successfully treated with gabapentin during rehabilitation. PMID- 22083265 TI - Cause-specific mortality following radical prostatectomy. AB - BACKGROUND: To evaluate cause-specific mortality following radical prostatectomy (RP) in a population cohort of US men adjusting for competing risks. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to identify 120,392 men undergoing RP for clinically localized prostate cancer between 1988 and 2003. Cause-specific mortality data were extracted through 2006 and cumulative incidence was estimated using a competing risks approach. RESULTS: The stage distribution of the cancers was 32% local, 28% regional, 40% unknown, and 80% of tumors Gleason <= 7. Median follow-up was 7 years. The 15-year prostate cancer-specific mortality was 5.3% and the non-prostate cancer mortality was 30.6%. Stage, grade and race had minimal impact on non-prostate cancer mortality. At 15 years following surgery, mortality due to cardiovascular diseases was 11%, other cancers 9.1%, and other causes 10.5%. Among men >= 65 years, 15-year cancer specific mortality was 6% and non-prostate cancer mortality was 40.8%. CONCLUSIONS: Following RP, death from cardiovascular diseases, other cancers, and other causes is far more common than death from prostate cancer. In men diagnosed with prostate cancer, significant efforts should be made to prevent, diagnose, and treat these diseases. PMID- 22083266 TI - Predictive value in the analysis of RNASEL genotypes in relation to prostate cancer. AB - BACKGROUND: We would like to compare the different RNASEL genotypes with the stage of the cancer using parameters such as PSA levels, Gleason score and T stage, and to develop a clinical protocol for the monitoring of the disease for trying a better evolution of the patient. METHODS: A total of 231 patients with sporadic prostate cancer and 100 of controls were genotyped in RNASEL gene by sequencing the exons 1 and 3. A survey of clinical information was collected by a specialist following the Helsinki protocol. All patients and controls were interviewed by a researcher and signed their informed consent to participation in the study, which was approved by Ethics Committee of the hospital. The genetic information was processed and collected with an ABI PRISM Genetic Analyser 3130 using SeqScape software v.2.6. All the patients were analysed by comparing the genetic and clinical data. chi(2)-tests, Monte Carlo, Fisher tests and contigency tables were performed using SPSS v.15.0 and ARLEQUIN v.3.5 software on patient population. RESULTS: Significant differences were found only between patients and controls in D541E, R461Q and I97L genotypes, the remainder of the variants did not seem relevant to our population in contrast to other populations, such as north-Caucasians, Afro Americans and Ashkenazi Jews. The genotypes associated with the worst prognoses are G/G in D541E, A/A in R462Q and A/G in I97L. The controls were included in our study to determine an approximation of the genotype in our population compared with the patients, but they did not account for the statistical process. CONCLUSIONS: The genetic profile of patients with this cancer combined with other parameters could be used as a prognosis factor in deciding to give more radical and frequent treatments, depending on personal genotype. PMID- 22083267 TI - Cyclin-dependent kinase inhibitor, P276-00, inhibits HIF-1alpha and induces G2/M arrest under hypoxia in prostate cancer cells. AB - BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation and controls genes involved in glycolysis, angiogenesis, migration and invasion. Overexpression of HIF-1alpha has been demonstrated in many common human cancers. METHODS: Luciferase reporter gene assay under hypoxia and normoxia was used to demonstrate transcriptional inhibition of HIF-1 by P276-00. Detailed studies such as western blotting, reverse-transcriptase-PCR and immunofluorescence were carried out to elucidate its mechanism of action. Cytotoxic potential of P276-00 under normoxia and hypoxia was determined on prostate cancer cells using CCK-8 assay, and cell-cycle analysis was carried out using flow cytometry. Antiangiogenic activity of P276-00 was demonstrated by migration assay and tube-formation assay. Efficacy study of P276-00 was performed in a PC-3 xenograft model. RESULTS: P276-00 inhibits transcriptional activation of HIF-1 under hypoxia. It suppressed hypoxia-mediated nuclear HIF-1alpha expression, as well as phosphorylation of Akt and 4E-BP1 and abrogated expression of HIF-1-inducible gene viz. vascular endothelial growth factor. Under hypoxia, P276-00 did not exhibit enhanced cytotoxic activity in prostate cancer cells but arrested them in the G2/M phase of the cell cycle. The tubular formation of human umbilical vein endothelial cells and migration of prostate cancer cells were also inhibited by P276-00 in vitro. In addition, it demonstrated significant in vivo efficacy in the PC-3 xenograft model. CONCLUSIONS: Given its low toxicity profile, its demonstrated antitumor activity and its potential to inhibit the HIF-1 pathway, P276-00 should be considered as antiangiogenic chemotherapy for prostate cancer. PMID- 22083268 TI - Visible light-driven CO2 reduction by enzyme coupled CdS nanocrystals. AB - Assemblies of carbon monoxide dehydrogenase molecules with CdS nanocrystals show fast CO(2) reduction driven by visible light. Activity is strongly influenced by size and shape of nanocrystals, and by the nature of the electron donor. PMID- 22083270 TI - Egg production and quality under three housing systems in the tropics. AB - The aim of this study was to evaluate egg production and quality of Rhode Island Red (RIR) laying hens in an outdoor system in the subhumid tropic. Eighty RIR laying hens were measured in two periods and housed randomly under three treatments: outdoor (O), indoor (I) and in conventional cages (C). Egg weight (55.88, 53.76 and 57.16 g, for O, I and C, respectively), food intake/hen/day (138.94, 129.74 and 162.90 g, for O, I and C, respectively) and food efficiency (3.13, 3.22 and 3.96 for O, I and C, respectively) were significantly (P < 0.05) influenced by housing system; however, both egg production and final body weight were not different (P > 0.05). Yolk colour (10.76, 9.94 and 10.08 colour scale, for O, I and C, respectively), albumen weight (92.63, 92.28 and 90.08 g, for O, I and C, respectively) and yolk weight (15.19, 14.61, 15.48 g for O, I and C, respectively) were significantly (P < 0.05) influenced by housing system, but albumen height, Haugh units and egg shell weight remained similar (P > 0.05). Under the conditions of this study, outdoor egg production seems to be a sustainable system comparable to the commercial type based on wired cages. PMID- 22083269 TI - Changes of vitamins A, E, and C and lipid peroxidation status of breeding and pregnant sheep during dry seasons on medium-to-low quality forages. AB - This study assessed the changes of plasma vitamin A, E, and C and the lipid peroxidation status of sheep during breeding and pregnancy under drought conditions. The study was conducted on 105 cross-bred fat tailed ewes, 3-5 years old with body condition scores (BCS) of 2.5 to 3.5. The ewes were grazing on medium-to-low quality forages during summer and low quality forages within the succeeding months and had ad libitum access to a mixture of alfalfa hay (40%) and wheat straw (60%) in the afternoons. From 3 weeks before breeding till 1 month after the introduction of rams, 300 g of barley grain/head/day was offered to the ewes and then the supplemental grain was reduced to 100 g/head/day. For better synchronization of estrus cycles in ewes, they were isolated from the rams for at least 2 months and then kept in close proximity of the rams for 1 week before the introduction of the rams to the ewe flock. Then, whole blood samples were collected on days 1, 7, 21, and 120 after ram introduction. Vitamins A, E, and C were measured in plasma. Malondialdehyde (MDA) was measured in the hemolysate as a biomarker of lipid peroxidation. Plasma progesterone (P4) was measured in the samples of day 120 for assessing pregnancy status of the ewes. Vitamins A and C showed continuous and significant declines (P < 0.05) through days 1 to 120. Vitamin E declined only during the first 21 days of the study and remained almost constant till day 120. MDA concentration increased significantly at day 21. An elevated concentration of MDA was also detected at day 120. The difference between days 21 and 120 was not significant (P > 0.05). A positive correlation between vitamins E and C was detected at day 120 (r = 0.349, P < 0.01). Age and BCS did not affect the patterns of changes. Assuming that the ewes with P4 concentrations >=2.5 ng/ml were pregnant, 95 out of 105 ewes (90.5%) were pregnant at day 120 of the study. Under the conditions of the present study with medium-to-low quality pastures as the main sources of feed, ewes of various ages and body conditions may suffer from oxidative stress during breeding and pregnancy. PMID- 22083271 TI - Implementation of herd health program to improve survival of Boer goats in Malaysia. AB - A Boer goat breeding farm with 800 heads of breeder females, 50 breeder males, and 400 growing goats of various ages in Sabah, Malaysia was selected to study the effect of implementing herd health program. This included vaccination program against pneumonic mannheimiosis; fecal monitoring for helminthiasis, coccidiosis, and colibacillosis; and introduction of modified feeding regime comprised of day time grazing and feeding of cut grass and supplemented feed. The herd health program was implemented in September 2007 and the impact was observed on body weight gains, body scoring, and annual mortality among adults and kids. It was found that implementation of herd health program significantly (p < 0.05) increased the average body weight gains in both adults and kids from 1.8 g per kid and 0.6 g per adult in 2006 to 3.7 g per kid and 2.2 g per adult in 2008. The percentage of adults with body scoring of <3 was significantly (p < 0.05) reduced from 82.3% in 2006 to 77.6% in 2007 and 4% in 2008. Similarly, the annual mortality rate was significantly (p < 0.05) reduced from 6.5% among kids and 58.2% among adults in 2006 to 12.1% among kids and 10.4% among adults in 2007, and to 9.1% among kids and 1.1% among adults in 2008. Therefore, it was concluded that implementation of herd health program significantly improved the survival and performance of goats. PMID- 22083272 TI - In vitro evaluation, in vivo quantification, and microbial diversity studies of nutritional strategies for reducing enteric methane production. AB - The main objective of the present work was to study nutritive strategies for lessening the CH(4) formation associated to ruminant tropical diets. In vitro gas production technique was used for evaluating the effect of tannin-rich plants, essential oils, and biodiesel co-products on CH(4) formation in three individual studies and a small chamber system to measure CH(4) released by sheep for in vivo studies was developed. Microbial rumen population diversity from in vitro assays was studied using qPCR. In vitro studies with tanniniferous plants, herbal plant essential oils derived from thyme, fennel, ginger, black seed, and Eucalyptus oil (EuO) added to the basal diet and cakes of oleaginous plants (cotton, palm, castor plant, turnip, and lupine), which were included in the basal diet to replace soybean meal, presented significant differences regarding fermentation gas production and CH(4) formation. In vivo assays were performed according to the results of the in vitro assays. Mimosa caesalpineaefolia, when supplemented to a basal diet (Tifton-85 hay Cynodon sp, corn grain, soybean meal, cotton seed meal, and mineral mixture) fed to adult Santa Ines sheep reduced enteric CH(4) emission but the supplementation of the basal diet with EuO did not affect (P > 0.05) methane released. Regarding the microbial studies of rumen population diversity using qPCR with DNA samples collected from the in vitro trials, the results showed shifts in microbial communities of the tannin-rich plants in relation to control plant. This research demonstrated that tannin-rich M. caesepineapholia, essential oil from eucalyptus, and biodiesel co-products either in vitro or in vivo assays showed potential to mitigate CH(4) emission in ruminants. The microbial community study suggested that the reduction in CH(4) production may be attributed to a decrease in fermentable substrate rather than to a direct effect on methanogenesis. PMID- 22083273 TI - Hydroxy-fatty acid production in a Pseudomonas aeruginosa 42A2 PHA synthase mutant generated by directed mutagenesis. AB - Pseudomonas aeruginosa 42A2 growing on waste frying oils is capable to synthesize polyhydroxyalkanoic acids (PHAs) and hydroxy-fatty acids as a result of several enzymatic conversions. In order to study the physiological role of PHA biosynthesis in P. aeruginosa with respect to the synthesis of hydroxy-fatty acids, an unmarked deletion mutant deficient for PHA biosynthesis was generated in P. aeruginosa 42A2. A combination of the sacB-based negative selection system with a cre-lox antibiotic marker recycling method was used for mutant isolation. Electron microscopy, nuclear magnetic resonance analysis, and transmission electron microscopy confirmed that PHA accumulation was completely abolished in the mutant strain. Interestingly, the new mutant strain showed higher carbon and oxygen uptake rate than the wild-type strain and higher efficiency in the conversion of oleic acid into (E)-10-hydroxy-8-octadecenic acid-octadecenoic acid. PMID- 22083274 TI - Heterologous expression system in Aspergillus oryzae for fungal biosynthetic gene clusters of secondary metabolites. AB - Fungal secondary metabolites have been considered promising resources in the search for novel bioactive compounds. Given the high potential of fungi as genetic resources, it is essential to find an efficient way to link biosynthetic genes to the product in a heterologous system, because many genes for the secondary metabolite in the original strain are silent under standard laboratory conditions. In a previous study, we constructed a heterologous expression system for a biosynthetic gene cluster using Aspergillus oryzae as the host. To make the host more versatile for the expression of secondary metabolism genes, the expression levels of a global regulator, laeA, were increased by placing the A. oryzae laeA gene under the control of the constitutive active pgk promoter. In the A. oryzae overexpressing laeA, two clusters of heterologous biosynthetic genes [the monacolin K (MK) gene cluster from Monascus pilosus and the terrequinone A (TQ) gene cluster from Aspergillus nidulans] were successfully overexpressed, resulting in the production of the corresponding metabolite, MK or TQ. The successful production of secondary metabolites belonging to different structural groups, namely MK as a polyketide and TQ as a hybrid of amino acid and isoprenoid, indicated that the laeA-enriched A. oryzae was a versatile host for the heterologous expression of the biosynthetic gene cluster. PMID- 22083276 TI - Cloning and overexpression of ketopantoic acid reductase gene from Stenotrophomonas maltophilia and its application to stereospecific production of D-pantoic acid. AB - Ketopantoic acid (KPA) reductase catalyzes the stereospecific reduction of ketopantoic acid to D-pantoic acid. Based on the N-terminal amino acid sequence of KPA reductase from Stenotrophomonas maltophilia 845, the KPA reductase gene was cloned from S. maltophilia NBRC14161 and sequenced. This gene contains an open reading frame of 777 bp encoding 258 amino acid residues, and the deduced amino acid sequence showed high similarity to the SDR superfamily proteins. An expression vector, pETSmKPR, containing the full KPA reductase gene was constructed and introduced into Escherichia coli BL21 (DE3) to overexpress the enzyme. Bioreduction of KPA using E. coli transformant cells coexpressing KPA reductase together with cofactor regeneration enzyme gene was also performed. The conversion yield of KPA to D-pantoic acid reached over 88% with a substrate concentration up to 1.17 M. PMID- 22083275 TI - N-glycans are not required for the efficient degradation of the mutant Saccharomyces cerevisiae CPY* in Schizosaccharomyces pombe. AB - In eukaryotic cells, aberrant proteins generated in the endoplasmic reticulum (ER) are degraded by the ER-associated degradation (ERAD) pathway. Here, we report on the ERAD pathway of the fission yeast Schizosaccharomyces pombe. We constructed and expressed Saccharomyces cerevisiae wild-type CPY (ScCPY) and CPY G255R mutant (ScCPY*) in S. pombe. While ScCPY was glycosylated and efficiently transported to the vacuoles in S. pombe, ScCPY* was retained in the ER and was not processed to the matured form in these cells. Cycloheximide chase experiments revealed that ScCPY* was rapidly degraded in S. pombe, and its degradation depended on Hrd1p and Ubc7p homologs. We also found that Mnl1p and Yos9p, proteins that are essential for ERAD in S. cerevisiae, were not required for ScCPY* degradation in S. pombe. Moreover, the null-glycosylation mutant of ScCPY, CPY*0000, was rapidly degraded by the ERAD pathway. These results suggested that N-linked oligosaccharides are not important for the recognition of luminal proteins for ERAD in S. pombe cells. PMID- 22083277 TI - Enzyme immobilization for biodiesel production. AB - Biodiesel has attracted more and more attention in recent years because of its biodegradability, environmentally friendliness, and renewability. Contrary to the conventional chemical catalysis method to produce biodiesel, the biochemical catalysis method developed quickly in the past decade and many immobilized enzymes are commercially available to meet the large-scale industrialization of biodiesel. This review is focusing on the current status of biodiesel production by biochemical catalysis method, especially the commercial enzyme and its immobilization for biodiesel production. Consequently, we believe that biochemical catalysis with immobilized enzymes is bound to be an alternative method instead of chemical catalysis in biodiesel production in the near future. PMID- 22083278 TI - Construction of a new recombinant protein expression system in the basidiomycetous yeast Cryptococcus sp. strain S-2 and enhancement of the production of a cutinase-like enzyme. AB - Yeast host-vector systems have been very successful in expressing recombinant proteins. However, because there are some proteins that cannot be expressed with existing systems, there is a need for new yeast expression systems. Here we describe a new host-vector system based on the basidiomycetous yeast Cryptococcus sp. strain S-2 (S-2). Two advantages of S-2 are that it naturally produces some very useful enzymes, so it would be a good system for expressing multiple copies of some of its genes, and that, it is a nonhazardous species. The orotate phosphoribosyltransferase (OPRTase, EC 2.4.2.10) gene (URA5) was selected as a selectable marker for transformation in the new host-vector system. URA5 was isolated and introduced into a uracil auxotroph of S-2 by electroporation. To demonstrate the S-2 system, we selected one of its unique enzymes, a plastic degrading cutinase-like enzyme (CLE). We were able to insert multiple copies of the CLE gene (CLE1) into the chromosomes in a high fraction of the targeted cells. Under optimal conditions, one transformant exhibited 3.5 times higher CLE activity than the wild type. Expression vectors, including an inducible promoter (the promoter for the xylanase or alpha-amylase gene), were constructed for recombinant protein production, and green fluorescent protein was expressed under the control of these promoters. The xylanase promoter was more tightly controlled. Furthermore, putting CLE1 under the control of the xylanase promoter, which is induced by xylose, increased CLE activity of the culture medium to approximately 15 times greater than that of the wild type. PMID- 22083279 TI - Wild-type and feedback-resistant phosphoribosyl pyrophosphate synthetases from Bacillus amyloliquefaciens: purification, characterization, and application to increase purine nucleoside production. AB - Bacillus strains are used for the industrial production of the purine nucleosides inosine and guanosine, which are raw materials for the synthesis of the flavor enhancers disodium inosinate and disodium guanylate. An important precursor of purine nucleosides is 5-phospho-alpha-D: -ribosyl-1-pyrophosphate, which is synthesized by phosphoribosyl pyrophosphate synthetase (PRS, EC 2.7.6.1). Class I PRSs are widespread in bacteria and mammals, are highly conserved among different organisms, and are negatively regulated by two end products of purine biosynthesis, adenosine 5'-diphosphate (ADP) and guanosine 5'-diphosphate (GDP). The D52H, N114S, and L129I mutations in the human PRS isozyme I (PRS1) have been reported to cause uric acid overproduction and gout due to allosteric deregulation and enzyme superactivity. In this study, to find feedback-resistant Bacillus amyloliquefaciens PRS, the influence of the D58H, N120S, and L135I mutations (corresponding to the D52H, N114S, and L129I mutations in PRS1, respectively) on PRS enzymatic properties has been studied. Recombinant histidine tagged wild-type PRS and three mutant PRSs were expressed in Escherichia coli, purified, and characterized. The N120S and L135I mutations were found to release the enzyme from ADP and GDP inhibition and significantly increase its sensitivity to inorganic phosphate (P(i)) activation. In contrast, PRS with the D58H mutation exhibited nearly identical sensitivity to ADP and GDP as the wild-type protein and had a notably greater P(i) requirement for activation. The N120S and L135I mutations improved B. amyloliquefaciens and Bacillus subtilis purine nucleoside producing strains. PMID- 22083280 TI - Simvastatin ameliorates angiotensin II-induced endothelial dysfunction through restoration of Rho-BH4-eNOS-NO pathway. AB - Endothelial dysfunction contributes to the initiation and development of hypertension. We previously found that simvastatin moderately decreases blood pressure in 2-kidney-2-clip (2k2c) renal hypertension, but the precise mechanisms are still unclear. The present study was designed to examine the protective actions of simvastatin in 2k2c-evoked endothelial dysfunction and also delineate the underlying mechanisms. Here we show that 2k2c-induced elevation in plasma angiotensin II impaired acetylcholine-induced endothelium-dependent vascular relaxation, suppressed endothelial NO synthase (eNOS) activity and reduced nitric oxide (NO) production. Additionally, the levels of tetrahydrobiopterin (BH4), an essential cofactor of eNOS, as well as the activity of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for BH4 synthesis, were markedly reduced. Administration of simvastatin significantly improved acetylcholine-induced endothelium-dependent carotid arteries relaxation at 9 weeks in reno-hypertensive rats. Notably, GTPCH I activity, BH4 production, p-eNOS expression and NO levels in the vascular endothelium were elevated as a result of simvastatin administration. In cultured rat arterial endothelial cells, simvastatin restored BH4, GTPCH I activity and NO release impaired by angiotensin II, and pretreatment with mevalonate (MVA) or geranylgeranyl pyrophosphate (GGPP) abolished the beneficial effects exerted by simvastatin. Moreover, RhoA inhibitor C3 exoenzyme, Rho kinase inhibitor Y-27632 and dominant negative mutant of RhoA prevented BH4 and NO loss due to Ang II treatment. Taken together, normalization of BH4-eNOS-NO pathway at least in part accounts for the beneficial actions of simvastatin on vascular endothelium during 2k2c hypertension, and RhoA-Rho kinase pathway is involved in regulation of BH4 production. PMID- 22083281 TI - [Neurological psychiatric medicolegal assessment]. PMID- 22083282 TI - [Drug treatment of epilepsy]. AB - Modern medical treatment of epilepsy renders two out of three newly diagnosed epilepsy patients seizure-free. More than 20 drugs are currently available and even for epilepsy specialists it may not be easy to select the drug which is best suited for the individual patient. Current guidelines recommend drugs with proven efficacy and optimal tolerability that address the individual needs of the patient. Non-enzyme-inducing agents are preferred if possible, to protect the patient from loss of efficacy when taking other medications for life-threatening disorders. In one out of three patients, seizure freedom is currently not possible due to drug-resistance, which requires a prompt diagnostic and therapeutic reevaluation of the epilepsy. PMID- 22083283 TI - Behavioral plasticity in an invaded system: non-native whelks recognize risk from native crabs. AB - Inducible defenses have the potential to affect both invasion success and the structure of invaded communities. However, little is known about the cues used for risk-recognition that influence the expression of inducible defenses in invasive prey, because they involve a novel threat. In laboratory experiments, we investigated behavioral defenses induced by a native crab on two invasive oyster drills (marine whelks Urosalpinx cinerea and Ocinebrina inornata). Both drills hid more often and reduced their feeding rates when they detected predators consuming conspecific prey. Examination of the responses of U. cinerea to specific cue sources (predator kairomones, conspecific alarm cues) indicated that this species had the strongest responses to cues from injured conspecifics, but that it did recognize the novel crab predator. Our observation of native predator (per se) recognition by an invasive marine prey is novel. In addition, we observed that neither species of drill reduced their defensive behavior to reflect predation risk shared by a group of prey. The lack of density dependence in risk-assessment could cause populations of invasive prey to transmit both quantitatively and qualitatively different community effects over the course of an invasion as abundance changes. Together, these findings demonstrate several ways that the risk-assessment strategies could be important in establishment and post-establishment dynamics of invasive prey. PMID- 22083284 TI - Non-linear effects of drought under shade: reconciling physiological and ecological models in plant communities. AB - The combined effects of shade and drought on plant performance and the implications for species interactions are highly debated in plant ecology. Empirical evidence for positive and negative effects of shade on the performance of plants under dry conditions supports two contrasting theoretical models about the role of shade under dry conditions: the trade-off and the facilitation hypotheses. We performed a meta-analysis of field and greenhouse studies evaluating the effects of drought at two or more irradiance levels on nine response variables describing plant physiological condition, growth, and survival. We explored differences in plant response across plant functional types, ecosystem types and methodological approaches. The data were best fit using quadratic models indicating a humped-back shape response to drought along an irradiance gradient for survival, whole plant biomass, maximum photosynthetic capacity, stomatal conductance and maximal photochemical efficiency. Drought effects were ameliorated at intermediate irradiance, becoming more severe at higher or lower light levels. This general pattern was maintained when controlling for potential variations in the strength of the drought treatment among light levels. Our quantitative meta-analysis indicates that dense shade ameliorates drought especially among drought-intolerant and shade-tolerant species. Wet tropical species showed larger negative effects of drought with increasing irradiance than semiarid and cold temperate species. Non-linear responses to irradiance were stronger under field conditions than under controlled greenhouse conditions. Non-linear responses to drought along the irradiance gradient reconciliate opposing views in plant ecology, indicating that facilitation is more likely within certain range of environmental conditions, fading under deep shade, especially for drought-tolerant species. PMID- 22083286 TI - Biphenotypic surface epithelial cells in the gastrointestinal tube with mixed epithelial-myofibroblastic differentiation: a paradigm. AB - Epithelial cells and myofibroblasts are well-characterized histomorphological elements of tissues. They are distinguished from one another on the basis of topography and of differences in cytokeratin (CK) and alpha-smooth muscle actin (SMA) expression. Certain epithelial cells exhibit CK / SMA co-expression. This study aimed to define the immunophenotypical characteristics of these biphenotypic cells with respect to cytodifferentiation (broad spectrum of CKs, SMA), cell-cell interaction (E-cadherin, adenomatous polyposis coli - APC, beta catenin), and cell survival (cyclooxygenase-2 - Cox-2). At the routine gastrointestinal pathology service of the Department of Pathology, University of Szeged, tissue samples were identified from instances of cervical inlet patch (n = 5), Barrett's esophagus (n=5), gastritis (n=5), fundic gland polyp (n=2), gastric neoplastic polyp (n=1), inflammatory bowel disease (n=5), and colonic neoplastic polyp (n=3). that contained epithelial cells expressing SMA. These biphenotypic cells were further immunophenotyped. Foregut-derived biphenotypic cells expressed CKs 7 and 20, while hindgut-derived biphenotypic cells expressed only CK 20. Subepithelial myofibroblasts adjacent to biphenotypic epithelium expressed Cox-2, SMA, and beta-catenin, as did biphenotypic cells. Myofibroblasts, however, did not express CKs. In neoplastic polyps, APC expression weakened as cytologic atypism increased, while intermingled biphenotypic cells in neoplastic glands overexpressed APC, as did myofibroblasts beneath. CK subspecies expression in biphenotypic cells reflects embryonic development of the gastrointestinal tract. The immunophenotyping analysis addresses bidirectional (via transdifferentiation from epithelia into myofibroblasts or vice versa) formation of biphenotypic cells within damaged epithelium, a phenomenon that must be further analysed. PMID- 22083287 TI - Labeling stem cells with ferumoxytol, an FDA-approved iron oxide nanoparticle. AB - Stem cell based therapies offer significant potential for the field of regenerative medicine. However, much remains to be understood regarding the in vivo kinetics of transplanted cells. A non-invasive method to repetitively monitor transplanted stem cells in vivo would allow investigators to directly monitor stem cell transplants and identify successful or unsuccessful engraftment outcomes. A wide range of stem cells continues to be investigated for countless applications. This protocol focuses on 3 different stem cell populations: human embryonic kidney 293 (HEK293) cells, human mesenchymal stem cells (hMSC) and induced pluripotent stem (iPS) cells. HEK 293 cells are derived from human embryonic kidney cells grown in culture with sheared adenovirus 5 DNA. These cells are widely used in research because they are easily cultured, grow quickly and are easily transfected. hMSCs are found in adult marrow. These cells can be replicated as undifferentiated cells while maintaining multipotency or the potential to differentiate into a limited number of cell fates. hMSCs can differentiate to lineages of mesenchymal tissues, including osteoblasts, adipocytes, chondrocytes, tendon, muscle, and marrow stroma. iPS cells are genetically reprogrammed adult cells that have been modified to express genes and factors similar to defining properties of embryonic stem cells. These cells are pluripotent meaning they have the capacity to differentiate into all cell lineages. Both hMSCs and iPS cells have demonstrated tissue regenerative capacity in-vivo. Magnetic resonance (MR) imaging together with the use of superparamagnetic iron oxide (SPIO) nanoparticle cell labels have proven effective for in vivo tracking of stem cells due to the near microscopic anatomical resolution, a longer blood half-life that permits longitudinal imaging and the high sensitivity for cell detection provided by MR imaging of SPIO nanoparticles. In addition, MR imaging with the use of SPIOs is clinically translatable. SPIOs are composed of an iron oxide core with a dextran, carboxydextran or starch surface coat that serves to contain the bioreactive iron core from plasma components. These agents create local magnetic field inhomogeneities that lead to a decreased signal on T2-weighted MR images. Unfortunately, SPIOs are no longer being manufactured. Second generation, ultrasmall SPIOs (USPIO), however, offer a viable alternative. Ferumoxytol (FerahemeTM) is one USPIO composed of a non-stoichiometric magnetite core surrounded by a polyglucose sorbitol carboxymethylether coat. The colloidal, particle size of ferumoxytol is 17-30 nm as determined by light scattering. The molecular weight is 750 kDa, and the relaxivity constant at 2T MRI field is 58.609 mM(-1) sec(-1) strength. Ferumoxytol was recently FDA-approved as an iron supplement for treatment of iron deficiency in patients with renal failure. Our group has applied this agent in an "off label" use for cell labeling applications. Our technique demonstrates efficient labeling of stem cells with ferumoxytol that leads to significant MR signal effects of labeled cells on MR images. This technique may be applied for non-invasive monitoring of stem cell therapies in pre-clinical and clinical settings. PMID- 22083288 TI - [Recommendations for sedation during flexible bronchoscopy]. AB - Flexible bronchoscopy is a standard examination today and is conducted not only in nearly every hospital but also in privately owned practices. The vast majority of patients want sedation for this examination. Such a procedure is nearly always necessary in complex and interventional procedures, irrespective of the patient's wish. The recommendation at hand to use sedation measures for flexible bronchoscopy is based on the results of numerous clinical studies and also takes account of individual experiences in this area. The structural and procedural requirements and the requirements for staff training are defined and should describe the minimum standard when it comes to conducting a bronchoscopy under sedation. Furthermore the drugs recommended for sedation are discussed and their methods of application shown. Finally the recommendations also include suggestions for patient clarification, monitoring and discharge. They should provide the examiner with concrete operating options and therefore above all increase patient safety. PMID- 22083289 TI - [New recommendations for contact tracing in tuberculosis]. PMID- 22083291 TI - [Obstructive airway disorders representing occupational diseases]. AB - Obstructive airway diseases, i. e., bronchial asthma and COPD, have a prevalence of about 5 % each in our population. 5 to 25 % of the cases are caused by the impact of hazardous substances in workplace atmospheres. Pathophysiologically and according to legal definitions on occupational diseases, allergic disorders (occupational disease no 4301) have to be differentiated from those of chemically irritative genesis (occupational disease no 4302 and predominantly also no 1315) and from afflictions in coal miners induced by inorganic dust (occupational disease no 4111). At present, hard coal mine dust is still the prevailing noxious agent followed by flour/baking additives, fumes occurring during welding, casting and cutting procedures, and isocyanates. In the majority of cases, the prognosis is not good and depends on the duration of exposure to the causative impact. This emphasises the urgency of early diagnosis and targetted individual prevention. The new international labelling of working materials hazardous to health (GHS; EU: CLP) also refers to inhalative noxae. It replaces the hitherto valid R und S notes by hazard statements (H) and precautionary statements (P) as well as by new hazard pictograms. PMID- 22083292 TI - [Cardiopulmonary exercise testing in occupational medical fitness examination and assessment]. AB - Medical expert opinion by occupational physicians and pneumologists has two main objectives: making a diagnosis with probability bordering on certainty and clarifying a causal relationship to a present or former occupational exposure to irritant toxic, allergenic or fibrosing dusts, gases, welding fumes or mineral fibres. Especially for conditions that are associated with exertional dyspnea, the diagnosis at rest using spirometry, body plethysmography, pulmonary function test, blood gas analysis, electrocardiogram and echocardiography is of limited use. This paper identifies the indications for cardiopulmonary exercise testing (CPET) in occupational medicine, explains the related measurements and their differential diagnostic value with special consideration of the flow-volume curve under exercise as well as the alveolar-arterial oxygen gradient. Diagnostic statements on the relevance of oxygen uptake measured at continuous and peak load compared to the wattage ascertained on the bicycle ergometer are presented. Characteristic CPET findings are explained in terms of their differential diagnostic significance. Furthermore, the importance of CPET for the assessment of occupational disease-related functional loss (clinical proportions in the reduction of working capacity) is shown. PMID- 22083293 TI - [Differential diagnosis and therapy of pulmonary diseases with angiitis and granulomatosis]. PMID- 22083294 TI - [In memory of Prof Dr. med. Hans-Ludwig Hahn]. PMID- 22083295 TI - Synthesis of 1,2,3-triazole-fused heterocycles via Pd-catalyzed cyclization of 5 iodotriazoles. AB - A convenient approach toward polycyclic frameworks containing fused 1,2,3 triazoles is described. The synthesis consists of a Cu-catalyzed cycloaddition and an intramolecular Pd-catalyzed direct arylation or Heck reaction, and affords the products in good to excellent yields. PMID- 22083296 TI - Angiogenesis and vasculopathy in systemic sclerosis: evolving concepts. AB - Systemic sclerosis (scleroderma [SSc]) is a multifactorial disease characterized by inflammation, extensive and progressive fibrosis, and multiple vasculopathies. The vascular manifestations can be seen early in the pathogenesis of the disease and include malformed capillaries, Raynaud's phenomenon, and digital ulcers. As the disease progresses, the vasculopathy proceeds to significant clinical manifestations, including renal crisis and pulmonary arterial hypertension. Moreover, later stages of the disease are marked by increasingly avascular areas. Despite the obliteration of microvascular structures, compensatory vasculogenesis and angiogenesis do not occur normally. This is in spite of a general increase in many potent angiogenic factors. Recent studies are beginning to examine this paradox and subsequent paucity of an angiogenic response in SSc. In this review, we discuss these findings and examine the role that chemokine and growth factor receptors, proteases, adhesion molecules, and transcription factors play in the dysregulation of angiogenesis in SSc. PMID- 22083297 TI - Extremity doses of nuclear medicine personnel: a concern. PMID- 22083298 TI - The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure. AB - PURPOSE: Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO(2)) in patients with chronic heart failure using (11)C-acetate positron emission tomography (PET). METHODS: We prospectively enrolled 21 patients with severe heart failure. (11)C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. RESULTS: Under resting conditions, the values of myocardial blood flow (MBF), MVO(2) and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 +/- 0.18 ml min(-1) g(-1) with the device off and 0.80 +/- 0.15 ml min(-1) g(-1) with the device on (p = 0.818), MVO(2) was 6.81 +/- 1.69 ml/min/100 g with the device off and 7.15 +/- 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 +/ 1.14 mmHg ml/m(2) with the device off and 5.21 +/- 1.36 mmHg ml/m(2) with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO(2) and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. CONCLUSION: These results indicate that CCM does not induce increased MVO(2), even under stress conditions. PMID- 22083299 TI - Profile and prevalence of malnutrition in children with spinal cord injuries assessment of the Screening Tool for Assessment of Malnutrition in Paediatrics (STAMP). AB - BACKGROUND: Data on the prevalence of malnutrition in paediatric patients with spinal cord injury (SCI) are limited. The present study aimed to establish the risk of (i) under-nutrition by using the Screening Tool for Assessment of Malnutrition in Paediatrics: STAMP (score >=2) and (ii) over-nutrition by body mass index (BMI) centile (>=91st: overweight; >=98th: obese). METHODS: After obtaining informed consent, a standardized questionnaire was used to collect baseline demographic data and nutrition risk score; BMI was measured and routine blood biochemistry was reviewed in every child (>6 months and <18 years) admitted to the SCI centre. RESULTS: Sixty-two children (mean age, 11.4 years; s.d., 4.9; median, 13 years; interquartile range, 7.8-15.6, 39.4% female) with SCI (46.5% tetraplegia, 53.4% complete SCI) were assessed. Prevalence of over-nutrition was high (BMI centile >=91st, 41.1%; >=98th, 25.5%). Under-nutrition risk was 47.1% (STAMP >=2). Only 60% of these 'at risk' patients were referred for further nutritional assessment. Associated phenomena included previous intensive care (55.6 versus 20.8%, P<0.05), mechanical ventilation (58.3 versus 18.2%, P<0.01) and past need for artificial nutrition support (75 versus 12.8%, P<0.01). CONCLUSIONS: Both over- and under-nutrition appear common in children with SCI. Our data indicate, furthermore, that children at nutritional risk are under managed. Future research is needed to complete the validation of the screening tools and to determine how effective intervention can be ensured. PMID- 22083300 TI - Characterization of H5N1 highly pathogenic avian influenza viruses isolated from poultry in Pakistan 2006-2008. AB - Nine avian influenza viruses (AIV), H5N1 subtype, were isolated from dead poultry in the Karachi region of Pakistan from 2006 to 2008. The intravenous pathogenicity indices and HA protein cleavage sites of all nine viruses were consistent with highly pathogenic AIV. Based on phylogenetic analysis of the HA genes, these isolates belong to clade 2.2 and both the HA and NA are closely related to each other (nucleotide identities above 99.0%) and to other Middle Eastern H5N1 AIV isolates (nucleotide identities above 98.0%). The phylogenetic data suggest that the virus in both epornitics of H5N1 HPAIV in commercial poultry in the Karachi region of Pakistan between 2006 and 2008 were from a very closely related source, however, there is inadequate epidemiological data to determine what the reservoir was for the virus between the 2006 and 2007 outbreaks other than that there was a single introduction into the region. PMID- 22083301 TI - Raising chickens in city backyards: the public health role. AB - There is increasing interest in raising chickens in urban settings across North America. Current regulations on backyard chickens vary by jurisdiction due to concerns about perceived health threats. Proposed negative impacts on public health and community well-being include infectious diseases acquired through rearing practices or consumption of eggs, inappropriate waste management, interaction with pests and predators and nuisance factors such as noise and odour. Proposed benefits are derived largely from the human-animal bond and from feelings of autonomy over food selection. The importance or validity of claims of positive and negative effects cannot be supported by literature specific to the urban agriculture context. Public health practitioners might approach this issue in a manner analogous to concerns over keeping domestic pets. PMID- 22083302 TI - Is the Y chromosome disappearing?--both sides of the argument. AB - On August 31, 2011 at the 18th International Chromosome Conference in Manchester, Jenny Graves took on Jenn Hughes to debate the demise (or otherwise) of the mammalian Y chromosome. Sex chromosome evolution is an example of convergence; there are numerous examples of XY and ZW systems with varying degrees of differentiation and isolated examples of the Y disappearing in some lineages. It is agreed that the Y was once genetically identical to its partner and that the present-day human sex chromosomes retain only traces of their shared ancestry. The euchromatic portion of the male-specific region of the Y is ~1/6 of the size of the X and has only ~1/12 the number of genes. The big question however is whether this degradation will continue or whether it has reached a point of equilibrium. Jenny Graves argued that the Y chromosome is subject to higher rates of variation and inefficient selection and that Ys (and Ws) degrade inexorably. She argued that there is evidence that the Y in other mammals has undergone lineage-specific degradation and already disappeared in some rodent lineages. She also pointed out that there is practically nothing left of the original human Y and the added part of the human Y is degrading rapidly. Jenn Hughes on the other hand argued that the Y has not disappeared yet and it has been around for hundreds of millions of years. She stated that it has shown that it can outsmart genetic decay in the absence of "normal" recombination and that most of its genes on the human Y exhibit signs of purifying selection. She noted that it has added at least eight different genes, many of which have subsequently expanded in copy number, and that it has not lost any genes since the human and chimpanzee diverged ~6 million years ago. The issue was put to the vote with an exact 50/50 split among the opinion of the audience; an interesting (though perhaps not entirely unexpected) skew however was noted in the sex ratio of those for and against the notion. PMID- 22083303 TI - Tracking chromosome dynamics in live yeast cells: coordinated movement of rDNA homologs and anaphase disassembly of the nucleolus during meiosis. AB - A prerequisite for determination of chromosome dynamics in live cells is development of a method for staining or marking the chromosome of interest. We describe here a unique chromosome-tracking system that differentially marks two large chromosome segments from homologs in the budding yeast Saccharomyces cerevisiae. Using yeast genetics and the special features at the repetitive ribosomal RNA (rRNA) gene cluster, we incorporated arrays of the tet operator and the lac operator into each repeat of the two rDNA homologs by homologous recombination. Expression of tet repressor-fused green fluorescent protein and lac repressor-fused red fluorescent protein in engineered cells led to the differential labeling of rDNA homologs. Using live-cell three-dimensional fluorescence microscopy, we showed that homologs undergo contraction and expansion cycles in an actin-dependent manner during meiosis and that chromosome mobility appears to be correlated with nuclear positioning. Our observations further revealed that, in contrast to mitosis, in meiosis the yeast nucleolus, the site of rRNA processing, was disassembled upon anaphase onset, suggesting a differential regulation of the rDNA array during meiotic chromosome segregation. Because rRNA genes are highly conserved, a similar chromosome-engineering approach may be adaptable in other eukaryotes for functional assays of chromosome organization in live cells. PMID- 22083304 TI - Ion currents induced by ATP and angiotensin II in cultured follicular cells of Xenopus laevis. AB - Xenopus laevis oocytes are commonly used to study the biophysical and pharmacological properties of foreign ion channels and receptors, but little is known about those endogenously expressed in their enveloping layer of follicular cells (FCs). Whole-cell recordings and the perforated patch-clamp technique in cultured FCs held at -60 mV revealed that ATP (20-250 MUM) generates inward currents of 465 +/- 93 pA (mean +/- standard error) in ~60% of the FCs studied, whereas outward currents of 317 +/- 100 pA were found in ~5% of the cells. The net effect of ATP on the FCs was to activate both mono- and biphasic inward currents, with an associated increase in membrane chloride conductance. Two microelectrode voltage-clamp recordings of nude oocytes held at -60 mV disclosed that ATP elicited biphasic inward currents, corresponding to the well-known F(in) and S(in)-like currents. ATP receptor antagonists like suramin, TNP-ATP, and RB2 did not inhibit any of these responses. On the other hand, when using whole-cell recordings, 1 MUM Ang II yielded smooth inward currents of 157 +/- 45 pA in ~16% of the FC held at -60 mV. The net Ang II response, mediated by the activation of the AT(1) receptor, was a chloride current inhibited by 10 nM ZD7155. This study will help to better understand the roles of ATP and Ang II receptors in the physiology of X. laevis oocytes. PMID- 22083305 TI - Jolkinolide B from Euphorbia fischeriana Steud induces apoptosis in human leukemic U937 cells through PI3K/Akt and XIAP pathways. AB - Jolkinolide B, a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud, is known to induce apoptosis in cancer cells. However, the molecular mechanism of its anti-cancer activity has not been fully elucidated. In the present study, we found that Jolkinolide B reduced cell viability and induced apoptosis in a dose- and time-dependent manner in human leukemic U937. The induction of apoptosis was also accompanied by the downregulation of PI3K/Akt and the inhibitor of apoptosis protein (IAP) family proteins. Moreover, we observed that Jolkinolide B treatment resulted in activation of caspase-3 and -9, which may partly explain the anti-cancer activity of Jolkinolide B. Taken together, our study for the first time suggest that Jolkinolide B is able to enhance apoptosis of U937 cells, at least in part, through downregulation of PI3K/Akt and IAP family proteins. Moreover, triggering of caspase-3 and -9 activation mediated apoptotic induction. PMID- 22083306 TI - Nuclear factor-kappaB2 represses Sp1-mediated transcription at the CD99 promoter. AB - Downregulation of the CD99 antigen on the surface of Hodgkin's lymphoma (HL) cells via EBV LMP1-mediated NF-kappaB suppression of Sp1 transcriptional activity is known to be associated with the appearance of pathogenic Reed-Sternberg cells. Here, we show that in addition, EBV LMP1 heterologous NF-kappaB activators such as CD30 and CD40 repress the CD99 promoter, which contains multiple Sp1-binding sites but no NF-kappaB binding sites. In addition, NF-kappaB-inducing kinase (NIK) repressed the CD99 promoter while NIK kinase mutants and JNK inhibitory protein failed to do so. Of the NF-kappaB subunits, NF-kappaB2 (p52) alone or in combination with other Rel subunits consistently inhibited the CD99, while NF kappaB1 (p50) showed a marginal repressive effect. Furthermore, while transfection of LMP1 repressed the CD99 promoter in wild-type or NF-kappaB1 deficient MEFs, the same repression was not observed in NF-kappaB2 (p52) deficient MEFs, indicating that NF-kappaB2 (p52) is required for LMP1-mediated repression of the CD99 promoter. Consistently, basal activity of the CD99 promoter was significantly higher in IKKalpha(-/-) and IKKbeta(-/-) MEFs, but not in IKKGamma(-/-) MEFs compared to the wild-type control MEFs. Sp1-binding sites were directly used in the repression, because a synthetic Sp1 reporter with 10 Sp1-binding sites from the CD99 promoter was repressed by LMP1 or p52 transfection. These data indicate that LMP1-mediated NF-kappaB2 exhibits the major inhibitory role in the transcription at the CD99 promoter. PMID- 22083308 TI - Dentinal sensitivity among a selected group of young adults in Nigeria. AB - BACKGROUND: There is paucity of data on the prevalence of dentinal sensitivity outside the hospital setting and impact of dentinal sensitivity among young adults in Africa. This study aimed to determine the prevalence and impact of dentinal sensitivity among young adults in Nigeria. MATERIALS AND METHODS: A cross-sectional survey was conducted among the undergraduates of University of Benin in August, 2010. Self-administered questionnaire elicited information on demography, self-reported dentinal sensitivity, the trigger factor, action taken, functional, and psychological impact. RESULTS: The prevalence of dentinal sensitivity was 211 (52.8%) among the participants and it was significantly higher in females than males (P=0.027). Participants experienced shocking sensation more on the left-side of the mouth. The most common trigger factor for the dentinal sensitivity was due to cold drink [169 (80.1%)]. Among the participants with dentinal sensitivity, majority [139 (65.9%)] have not taken any action and only 24 (11.4%) have visited the dentist because of the problem. Dentinal sensitivity exhibited psychological impact among the participants as 64 (30.3) reported unhappiness due to the shocking sensation. Eating and talking were disturbed, respectively, in 59 (28.0%) and 12 (5.7%) of the participants. CONCLUSION: The prevalence of dentinal sensitivity was high which was significantly higher in females than males. Despite the negative functional and psychological impact among the participants, only a few sought dental professional care. Screening for dentinal sensitivity at community level is required to proffer early treatment and ameliorate its impact on the populace. PMID- 22083307 TI - Time-dependent changes in lipid metabolism in mice with methionine choline deficiency-induced fatty liver disease. AB - Methionine and choline-deficient diet (MCD)-induced fatty liver is one of the best-studied animal models of fatty liver disease. The present study was performed to clarify the relative contributions of individual lipid metabolic pathways to the pathogenesis of MCD-induced fatty liver. Hepatic lipogenesis mediated by the sterol regulatory element-binding protein (SREBP-1c) was increased at 1 week, but not at 6 weeks, of MCD feeding. On the other hand, (14)C palmitate oxidation did not change at 1 week, but significantly decreased at 6 weeks. This decrease was associated with increased expression of fatty acid translocase, a key enzyme involved in fatty acid uptake. Expression of endoplasmic reticulum stress markers was increased in mice given MCD for both 1 and 6 weeks. These findings suggest the presence of time-dependent differences in lipid metabolism in MCD-induced fatty liver disease: SREBP-1c-mediated lipogenesis is important in the early stages of fatty liver disease, whereas increased fatty acid uptake and decreased fatty acid oxidation become more important in the later stages. PMID- 22083309 TI - [New ultrasound technologies for the diagnostics of prostate cancer]. AB - CLINICAL/METHODOLOGICAL ISSUE: Prostate cancer is the most common cancer in men. The diagnosis is based on prostate-specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasound (TRUS) guided biopsy. These techniques have considerable limitations, which result in unnecessary biopsies. Furthermore the biopsies are associated with morbidity and costs. STANDARD RADIOLOGICAL METHODS: Standard gray-scale ultrasound has a low sensitivity and specificity for prostate cancer detection. METHODOLOGICAL INNOVATIONS: New ultrasound technologies, including color- and power Doppler ultrasound, contrast enhanced US and real-time sonoelastography have shown to improve prostate cancer diagnosis. PERFORMANCE: Contrast-enhanced ultrasound has shown a sensitivity of 100% (95% CI, 95%), a negative predictive value (NPV) of 99.8% and a positive predictive value (PPV) of 88.8% for prostate cancer detection. Real-time sonoelastography has shown a sensitivity of 86%, a specificity of 81% and NPV of 91% for prostate cancer diagnosis. ACHIEVEMENTS: Most studies show that these new ultrasound modalities demonstrate a 1.5 to 2.5 times higher detection of prostate cancer per biopsy specimen compared with systematic biopsy. Multicenter studies results are at present lacking but are, however ongoing. PRACTICAL RECOMMENDATIONS: In patients with suspected prostate cancer (elevated PSA, suspicious DRE) these new ultrasound techniques should be used. These techniques can detect prostate cancer and allow a targeted biopsy approach. PMID- 22083310 TI - [CT-guided biopsies and drainage]. AB - Following the implementation of computed tomography (CT) or ultrasound-guided biopsy of solid tumors and the puncture and drainage of liquid processes, the number of surgical open biopsies and curative operations for abscess drainage has declined. Such CT-guided interventions are performed in nearly every organ. Instead of aspiration biopsies, more and more core biopsies are being performed to allow histopathological evaluation and thus allowing targeted therapy.This article is intended to give a general overview of techniques, materials, indications and contraindications. Ultrasound-guided biopsies as well as large bore vacuum biopsies of the breast are not included in this review. PMID- 22083312 TI - Changes in coagulation and hemodynamics during pregnancy: a prospective longitudinal study of 58 cases. AB - PURPOSE: To investigate changes and establish reference values in coagulation, anticoagulation, fibrinolysis, anti-fibrinolysis and hemodynamics during normal pregnancy. METHODS: A total of 58 women with singleton pregnancies were recruited. Blood and ultrasound examinations were performed in the 10th-14th, 20th-24th, and 30th-34th weeks of pregnancy. The same examinations were performed in 50 non-pregnant women who were selected as the control group. RESULTS: Levels of fibrinogen, thrombin time, fibronectin, prothrombin activated fragments 1+2 and thrombomodulin were higher in early pregnancy than those in the control group (P < 0.05). Fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time, thromboxane B2, prothrombin activated fragments 1+2, thrombomodulin, D-dimer, and plasminogen activator inhibitor-2 were statistically different between the mid pregnancy and the control group (P < 0.05). Meanwhile, fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time, fibronectin, thromboxane B2, prothrombin activated fragments 1+2, thrombomodulin, and plasminogen activator inhibitor-2 were obviously elevated in late pregnancy as compared with the control group (P < 0.05). Moreover, fibrinogen, thromboxane B2, prothrombin activated fragment 1+2, D-dimer plasminogen, and activator inhibitor-2 gradually increased during pregnancy with some fluctuation. Prothrombin time, activated partial thromboplastin time, thrombin time, international normalized ratio, and thrombomodulin as well as systolic/diastolic ratio, pulsatility index, and resistance index in uterine arteries showed a tendency to decrease in pregnant women. CONCLUSIONS: Coagulation, anti-coagulation, fibrinolytic and anti-fibrinolytic activities are enhanced and balanced at a higher level during pregnancy. In addition, uterine artery and umbilical artery hemodynamics become more baby friendly (i.e., high flow and low resistance). PMID- 22083313 TI - Critical analysis of risk factors for shoulder dystocia. AB - OBJECTIVE: The study was aimed to define trends, risk factors and perinatal outcome associated with shoulder dystocia (SD). METHODS: A population-based study comparing all singleton deliveries with and without SD was conducted. Statistical analysis was performed using multiple logistic regression analysis. RESULTS: Shoulder dystocia complicated 0.2% (n = 451) of all deliveries included in the study (n = 240,189). The rate of SD declined from 0.4% in 1988 to 0.13% in 2009. Independent risk factors for SD in a multivariable analysis were fetal macrosomia (birth-weight >= 4 kg; OR = 16.1; 95% CI 13.2-19.6, P < 0.001), failure of labor to progress during the second stage (OR = 2.4; 95% CI 1.5-3.7, P < 0.001), diabetes mellitus (OR = 1.8; 95% CI 1.4-2.3, P < 0.001) and advanced maternal age (years, OR = 1.02; 95% CI 1.001-1.03, P = 0.029). Perinatal mortality was significantly higher after SD as compared to the comparison group (6.2 vs. 1.4%, P <0.001). Another multivariable analysis, with perinatal mortality as the outcome variable, controlling for confounders such as maternal age, gestational age, diabetes mellitus, etc. was constructed; SD was noted as an independent risk factor for perinatal mortality (adjusted OR = 11.1; 95% CI 7.2-17.1, P < 0.001). CONCLUSIONS: Shoulder dystocia, associated with macrosomia, labor dystocia, diabetes mellitus, and advanced maternal age, is an independent risk factor for perinatal mortality. In an era of increased rate of cesarean deliveries, and perhaps increased accuracy of birth weight estimation, the rate of shoulder dystocia gradually declines. PMID- 22083314 TI - Effect of rosehip (Rosa canina L.) phytochemicals on stable free radicals and human cancer cells. AB - BACKGROUND: The commercial development of plants as sources of antioxidants that can be used to enhance the properties of foods, for nutritional purposes and preservation as well as for prevention of oxidation-related diseases, is currently of major interest. Rosehip (Rosa canina L.) is a rich source of vitamin C and polyphenols. RESULTS: Phytochemicals in rosehip tea were separated into three fractions: Fr1 (vitamin C, 39.17 mg kg(-1)), Fr2 (flavonoids, 451.05 ug kg( 1)) and Fr3 (phenolic acids, 504.69 ug kg(-1)). Quercetin and ellagic acid were the most abundant polyphenolic compounds. Rosehip fractions, primarily rosehip flavonoids (EC(50) = 49 mg L(-1)), showed high antioxidant activity towards 2,2 diphenyl-1-picrylhydrazyl radicals (DPPH(*)). Cell growth effects of rosehip fractions were assessed in HeLa, MCF7 and HT-29 cell lines, with the lowest IC(50) values being determined for rosehip flavonoids, (80.63, 248.03 and 363.95 mg L(-1) respectively). However, the vitamin C fraction did not inhibit the growth of tested tumour cells. CONCLUSION: The results of this study confirm that vitamin C and flavonoids are responsible for the antioxidant activity of rosehip tea, while only polyphenols contribute to its antiproliferative activity. PMID- 22083316 TI - Adhesion frequency assay for in situ kinetics analysis of cross-junctional molecular interactions at the cell-cell interface. AB - The micropipette adhesion assay was developed in 1998 to measure two-dimensional (2D) receptor-ligand binding kinetics. The assay uses a human red blood cell (RBC) as adhesion sensor and presenting cell for one of the interacting molecules. It employs micromanipulation to bring the RBC into contact with another cell that expresses the other interacting molecule with precisely controlled area and time to enable bond formation. The adhesion event is detected as RBC elongation upon pulling the two cells apart. By controlling the density of the ligands immobilized on the RBC surface, the probability of adhesion is kept in mid-range between 0 and 1. The adhesion probability is estimated from the frequency of adhesion events in a sequence of repeated contact cycles between the two cells for a given contact time. Varying the contact time generates a binding curve. Fitting a probabilistic model for receptor-ligand reaction kinetics to the binding curve returns the 2D affinity and off-rate. The assay has been validated using interactions of Fcgamma receptors with IgG Fc, selectins with glycoconjugate ligands, integrins with ligands, homotypical cadherin binding, T cell receptor and coreceptor with peptide-major histocompatibility complexes. The method has been used to quantify regulations of 2D kinetics by biophysical factors, such as the membrane microtopology, membrane anchor, molecular orientation and length, carrier stiffness, curvature, and impingement force, as well as biochemical factors, such as modulators of the cytoskeleton and membrane microenvironment where the interacting molecules reside and the surface organization of these molecules. The method has also been used to study the concurrent binding of dual receptor-ligand species, and trimolecular interactions using a modified model. The major advantage of the method is that it allows study of receptors in their native membrane environment. The results could be very different from those obtained using purified receptors. It also allows study of the receptor-ligand interactions in a sub-second timescale with temporal resolution well beyond the typical biochemical methods. To illustrate the micropipette adhesion frequency method, we show kinetics measurement of intercellular adhesion molecule 1 (ICAM-1) functionalized on RBCs binding to integrin alpha(L)beta(2) on neutrophils with dimeric E-selectin in the solution to activate alpha(L)beta(2). PMID- 22083318 TI - Minimally invasive treatment of rectovaginal fistula. AB - BACKGROUND: Rectovaginal fistulas (RVFs) are a rare surgical condition. Their treatment is extremely difficult, and no standard surgical technique is accepted worldwide. This report describes a new approach using transanal endoscopic microsurgery (TEM) to treat RVFs. METHODS: A retrospective review of 13 patients who underwent repair of rectovaginal fistula using TEM between 2001 and 2008 was undertaken. The surgical technique is widely described, and the advantages of the endorectal approach are noted. RESULTS: The median follow-up period was 25 months, and the median age of the patients was 44 years (range, 25-70 years). The mean operative time was 130 min (range, 90-150 min), and the hospital stay was 5 days (range, 3-8 days). One patient experienced recurrence. This patient underwent reoperation with TEM and experienced re-recurrence. Two patients had minor complications (hematoma of the septum and abscess of the septum), which were treated with medical therapy. For two patients, a moderate sphincter hypotonia was registered. CONCLUSIONS: A new technique for treating RVFs using TEM is presented. The authors strongly recommend this approach that avoids any incision of the perineal area, which is very painful and can damage sphincter functions. PMID- 22083319 TI - Video. Repeated transvaginal notes: is it possible? AB - PURPOSE: Transvaginal surgery has been performed by gynecologists for decades with abundant literature supporting its efficacy and safety. Recently, several groups reported on the NOTES transvaginal (TV) approach for extrapelvic disease. Nevertheless, repeated TV access for NOTES has never been reported to date. Two cases of "repeated" TV access for NOTES cholecystectomy after TV hybrid sleeve gastrectomy are described. METHODS: Two women, aged 57 and 32 years, developed symptomatic cholelithiasis respectively 6 and 8 months after TV sleeve gastrectomy for morbid obesity. Sleeve gastrectomy: a 2-cm posterior colpotomy was performed under laparoscopic control between the uterosacral ligaments. A double-channel endoscope and a 60-cm-long laparoscopic grasper were introduced transvaginally. Two abdominal ports were placed to allow the introduction of the stapling device and to assist during the procedure. An intragastric endoscope served to expose the stomach and to calibrate the gastric sleeve, which was performed in the standard fashion. Colpotomy was closed by separate 3/0 Vicryl stitches. At cholecystectomy, an exploratory laparoscopy ascertained the feasibility of a NOTES cholecystectomy. The posterior vaginal vault was carefully examined before regaining peritoneal access with the technique described above. Cholecystectomy was performed by using a double-channel endoscope introduced TV and a 5-mm transabdominal port. Follow-up consisted of 3 and 6 months pelvic examination and interview, which included sexual function assessment by sexual function questionnaire (SFQ31). RESULTS: Both operations were performed successfully with no intraoperative or postoperative complications. At cholecystectomy, minimal pelvic adhesions were found with no vaginal scarring at the colpotomy site. No bleeding, pain, or vaginal infection occurred after both procedures. Patients resumed sexual activity 5.2 weeks postoperatively with a consistently normal SFQ31. CONCLUSIONS: This report suggests that, in experienced hands, repeated TV access for extrapelvic surgery is possible and safe, putting forward the intriguing promises of less adhesions formation. PMID- 22083320 TI - Plasma from the second and third weeks after open colorectal resection for cancer stimulates in vitro endothelial cell growth, migration, and invasion. AB - INTRODUCTION: Angiogenesis is central to wound healing and tumor growth. Postoperative (postop) plasma from weeks 2 and 3 after minimally invasive colorectal resection (MICR) stimulates endothelial cell (EC) migration (MIG), invasion (INV), and proliferation (all vital to angiogenesis) compared with preoperative (preop) plasma results and may promote postop tumor growth. The purpose of this study was to determine whether plasma from open colorectal resection (OCR) patients has similar proangiogenic EC effects in vitro. METHODS: OCR cancer patient plasma from institutional review board-approved banks was used; patients with preop and one postop sample from postoperative days (POD) 7 33 were eligible. Samples were bundled into 7- to 13-day periods and considered as single time points. In vitro cultures of human umbilical venous ECs were used for the EC proliferation (BPF, Branch Point Formation), INV, and MIG assays performed with preop, POD 7-13, POD 14-20, and POD 21-33 plasma. Data were analyzed by paired t test and were reported as mean +/- standard deviation (significance, P < 0.05). RESULTS: Plasma from 53 cancer patients (25 rectal and 28 colon) was used. Because of limited postop samples, the number for each time point varies: POD 7-13, n = 30; POD 14-20, n = 26; and POD 21-33, n = 17. In vitro EC BPF was significantly greater at the POD 7-13 (P < 0.0001) and POD 14-20 (P < 0.0001) time points versus preop results. Significantly greater EC INV and MIG were noted on POD 7-13 and POD 14-20 versus the preop plasma results (P < 0.0001). In regards to POD 21-33, a significantly greater result was noted only for the INV assay versus preop. CONCLUSIONS: Plasma from weeks 2 and 3 after OCR stimulates in vitro EC BPF, INV, and MIG. A significant difference from preop baseline was noted only for the INV assay in week 4. The OCR and previous MICR results were largely similar. Tumor angiogenesis may be stimulated after OCR and MICR for 3 weeks. Further studies are warranted. PMID- 22083322 TI - Single-incision laparoscopic cholecystectomy using a modified dome-down approach with conventional laparoscopic instruments. AB - INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) may increase the risk of bile duct injury due to compromised operative exposure. Dome-down laparoscopic cholecystectomy provides the ability to evaluate the cystic duct circumferentially prior to its division, thus minimizing the risks of bile duct injury. This study assesses the feasibility and safety of SILC using a modified dome-down approach with all conventional laparoscopic instruments. METHODS: Three low-profile 5-mm trocars are placed via a single transumbilical incision. The two working trocars are aimed laterally via the rectus to achieve adequate triangulation. An extralong 5-mm 30o laparoscope with an L-shaped light-cord adaptor is used to yield more external working space. Cephalic liver retraction is achieved with one transabdominal suture through the gallbladder fundus. Leaving the gallbladder fundus attached to the liver bed, a window is first created between the gallbladder body and the liver. The dissection is then carried down retrograde toward the porta hepatis. A 360o view of the gallbladder cystic duct junction is achieved prior to transecting the cystic duct. The gallbladder is then freed by separation of the fundal attachments. The specimen is retrieved by enlarging the fascial incision. All fascial defects are then primarily closed. RESULTS: Sixteen patients (mean age 31 years, mean BMI 26.3 kg/m(2)) were enrolled in this study. Thirteen had elective surgery for symptomatic cholelithiasis, and three had emergency surgery for acute cholecystitis. Mean operating time was 80.3 min, and blood loss was minimal. All patients were discharged within 24 h without complications. Follow-up at 1 month revealed a barely visible scar within the umbilicus. CONCLUSIONS: SILC using a modified dome-down approach is technically feasible with all straight instruments, and it is safe because of good delineation of ductal anatomy. Adoption of this approach may minimize the risk of bile duct injury during early experience of SILC. PMID- 22083321 TI - Effects of laparoscopic Roux-en-Y gastric bypass on glucose-6 phosphate dehydrogenase activity in obese type 2 diabetics. AB - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway that provides the majority of NADPH required for lipid biosynthesis. G6PD overexpression has been implicated in insulin resistance, hyperlipidemia, and increased oxidative stress in animals. This study examines G6PD expression in obese diabetic and nondiabetic subjects pre- and post laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Patients undergoing LRYGB were recruited for the IRB-approved study and placed in either the diabetic (n = 11) or nondiabetic group (n = 16) (diabetic, HbA1c > 6.5%; nondiabetic, HbA1c < 6.0%). Blood samples were collected at baseline and throughout the first 3 postoperative months. Liver, adipose, and omental samples were taken during surgery. Results are expressed as mean +/- SEM and were compared statistically using the Mann-Whitney test. RESULTS: The two groups were not significantly different at baseline except for fasting glucose and HbA1c. G6PD activity (nm/min/mg protein) was significantly higher in red blood cells (RBCs) (3.12 +/- 1.39 vs. 0.67 +/- 0.14) and liver (17.23 +/- 2.40 vs. 9.74 +/- 2.18) in diabetics compared to nondiabetics. There was good correlation between increased liver G6PD activity and the severity of diabetes as measured by HbA1c (r (2) = 0.525) and fasting glucose (r (2) = 0.542). No significant difference was found in the adipose or omental G6PD expression. Both groups experienced a significant increase in G6PD blood activity shortly following surgery (1 week) followed by a reduction 3 months after surgery. CONCLUSION: These results are the first ever seen in human subjects and demonstrate increased G6PD activity in diabetics compared to nondiabetics. These results suggest a correlation between G6PD activity and the severity of type 2 diabetes. The early increases in G6PD activity after LRYGB were unexpected and longer follow-up is needed to determine the effects of LRYGB on G6PD activity. PMID- 22083323 TI - Multimedia manuscript. Thoracoscopic management of chylothorax after esophagectomy. AB - BACKGROUND: Chylothorax after esophagectomy is a potentially life-threatening complication, with a reported incidence rate of 1-4%. Two cases of postoperative chylothorax successfully managed thoracoscopically are reported. METHODS: In case 1, a 61-year-old man presenting with an adenocarcinoma of the lower esophagus underwent laparoscopic transhiatal esophagectomy after neoadjuvant chemotherapy. The thoracic duct was identified, and no obvious leaks were detected. The thoracic drain was removed on postoperative day (POD) 6, and chest X-rays were normal. The patient was discharged on POD 10. On POD 20, he was readmitted for acute cardiopulmonary distress. Computed tomography scan showed a massive right collection. After insertion of a chest tube, 8 l of chylous fluid were drained. Once hemodynamic stabilization had been established, the patient was scheduled for surgery. In case 2, a 54-year-old woman presenting with esophageal stenosis after caustic injury refractory to balloon dilation and stenting underwent esophagectomy. Mediastinal dissection was difficult due to fibrotic reaction. On POD 2, the patient presented with a massive chylothorax. In both cases, three trocars were inserted in the right pleural cavity. An incomplete lateral injury of the thoracic duct was found in case 1, and a complete transection proximal to the cervical anastomosis next to the left subclavian was found in case 2. Clips and sutures were used first to seal the duct. Fibrin glue was applied to reinforce the closure. A chest tube was left in place. RESULTS: The operative time was 60 min in case 1 and 55 min in case 2. The chylothorax did not recur, although the postoperative course was longer in case 2 due to associate comorbidities. CONCLUSIONS: The thoracic duct is exposed to injuries during esophagectomies, especially in cases of cancer and postcaustic injuries, leading to fibrotic reaction of the surrounding tissue. Early and delayed chylothorax can be managed efficiently by a thoracoscopic approach replicating the sealing techniques used in thoracotomy. PMID- 22083324 TI - Single-stage treatment with intraoperative ERCP: management of patients with possible choledocholithiasis and gallbladder in situ in a non-tertiary Spanish hospital. AB - BACKGROUND: The best way to reduce endoscopic retrograde cholangiopancreatography (ERCP) complications is not to perform it if it is unnecessary. Both intraoperative and postoperative ERCP rely on use of intraoperative cholangiography as a final diagnostic test for choledocholithiasis (CLD) whenever clinical data are unable to rule out CLD. Intraoperative ERCP could become a therapeutic option when a previous preoperative ERCP fails. We present our experience with intraoperative ERCP. PATIENTS AND METHODS: This is a descriptive and prospective study of a cohort of 82 patients with moderate risk of CLD. They were operated on by laparoscopic cholecystectomy with intraoperative cholangiography (IOC). We performed intraoperative ERCP using the rendezvous technique. RESULTS: Thirty-six out of 82 patients had an abnormal IOC study. Mean age was 58.7 years (standard deviation, SD 16.6, 25-83 years), and 60.6% were females. Ultrasound study showed that 51.4% of patients had a dilated bile duct. Magnetic resonance cholangiography (MRC) was performed on three patients (8.3%). The success rate of intraoperative ERCP was 88.2%. Three out of the 36 patients (8.8%) had ERCP complications [2 mild papillary bleeding (5.8%), 1 acute pancreatitis (2.9%)]. The rate of conversion to open surgery was 5% with a surgical complications rate of 4% [one injured duct and two surgical bleeding which required re-operation (2.5%)]. There were no mortalities. Four patients (11.1%) needed post-surgical ERCP, with a residual CLD rate of 5.6% (two patients) in the postoperative period. Mean surgical time was 181 min (SD 60, 75 345 min). Mean hospital stay was 6.2 days (SD 4.7, 2-24 days). CONCLUSIONS: Intraoperative ERCP is an option to prevent performing ERCP unnecessarily on patients with moderate risk of CLD not confirmed using appropriate radiological studies. It can resolve the biliary disease in a single step with a similar success rate to standard ERCP, but with low morbidity, especially of acute pancreatitis. The residual CLD rate is also very low. PMID- 22083325 TI - Laparoendoscopic single-site surgery versus conventional laparoscopic varicocele ligation in men with palpable varicocele: a randomized, clinical study. AB - OBJECTIVE: This study was designed to compare the outcomes of two different surgical techniques: conventional transperitoneal laparoscopic varicocele ligation (CTL-VL), and laparoendoscopic single-site varicocele ligation (LESS VL), using transumbilical home-made single port device. METHODS: Our sample included 82 male patients with 92 clinically palpable varicoceles who underwent varicocelectomy. The patients were randomly allocated to one of two groups according to varicocele ligation technique. Early postoperative complications, hospital stay, time to return to work, degree of satisfaction, and semen parameters were assessed. A visual analogue scale (VAS) pain score that ranged from 0 to 10 and analgesia requirements during the postoperative course were used to evaluate postoperative pain. RESULTS: The operating room time and hospital stay of the two study groups were comparable, but time to return to normal activity was significantly shorter in the LESS group compared with the CTL group (P = 0.025). Both VAS and the postoperative use of analgesics were significantly lower during postoperative days 2 (P = 0.005) and 3 (P = 0.047) in patients who underwent LESS-VL compared with patients who underwent CTL-VL. Significant improvements in sperm count, motility, and morphology were observed in both groups (P < 0.001; at each of the variables in both groups), but the proportion of patients who showed improvement was not significantly different between the two groups. CONCLUSIONS: This relatively small-scale study suggests that LESS-VL is a safe and effective alternative to CTL-VL that provides surgeons with a minimally invasive surgical option and the ability to hide the surgical incision within the umbilicus. PMID- 22083326 TI - A comparative study of multiport versus laparoendoscopic single-site adrenalectomy for benign adrenal tumors. AB - BACKGROUND: The safety and feasibility of laparoendoscopic single-site (LESS) adrenalectomy for benign adrenal lesions was proved in early clinical series. However, the advantages of LESS over multiport laparoscopic adrenalectomy still are under investigation. METHODS: Since October 2009, the authors have prospectively performed LESS retroperitoneal adrenalectomy for 21 consecutive patients with benign adrenal tumors (LESS group). Another 28 patients with benign adrenal tumors were prospectively collected between June 2006 and October 2009 and served as a multiport laparoscopic adrenalectomy group. The patients' demographic data, operating time, estimated blood loss, peri- and postoperative complications, and short-term outcome were collected for further analysis. RESULTS: The demographic data were comparable between the two groups in terms of the patient age, gender, body mass index (BMI), laterality, diagnosis, and resected specimen weight. No major complication or mortality occurred in either group. Neither group had any conversions. No differences were observed between the two groups in terms of intraoperative hemodynamic status or peri- or postoperative complications. The LESS patients had quicker resumption of oral intake (0.18 vs 1 day; p < 0.001), a shorter hospital stay (2 vs 4 days; p < 0.001), and a reduced analgesic requirement postoperatively (0 vs 0.84 mg/kg; p = 0.023) than the multiport laparoscopic patients. CONCLUSIONS: The results demonstrate that LESS adrenalectomy is as safe and effective as conventional multiport laparoscopic adrenalectomy for benign adrenal tumors. In addition, LESS adrenalectomy provides short-term convalescence advantages over multiport laparoscopic adrenalectomy. PMID- 22083327 TI - Mesh fixation with a barbed anchor suture results in significantly less strangulation of the abdominal wall. AB - BACKGROUND: Laparoscopic ventral hernia repair using an underlay mesh frequently requires suture fixation across the abdominal wall, which results in significant postoperative pain. This study investigates the utility of a novel mesh fixation technique to reduce the strangulation force on the abdominal wall. METHODS: Multiple 2-cm(2) pieces of polyester mesh (Parietex Composite, Covidien) were placed as an underlay against a porcine abdominal wall. Fixation was accomplished using either the standard 0-polyglyconate or the 0-polyglyconate barbed anchor suture designed to hold in tissue without the need to tie a knot (V-Loc 180; Covidien). Suture fixation began with a stab wound incision in the skin. A suture passing device then was used to pass the suture across the abdominal wall and through the mesh. The suture passer was removed and reintroduced through the same stab wound incision but at a different fascial entry point 1.5 cm away. The tail of the suture was grasped and pulled up through both the mesh and the abdominal wall, creating a full-thickness U-stitch. One tail of the suture was attached to a tensiometer, and the strangulation force on the abdominal wall was measured while the suture was tied (standard) or looped (barbed). To compare pullout force, the tensiometer was attached to either the mesh or the suture, and traction was applied until material failure or suture pull through. Results are expressed as mean +/- standard deviation. Comparisons were performed using Student's t-test. RESULTS: Eight pieces of mesh were placed for each suture. The average force required to secure the barbed suture (0.59 +/- 0.08 kg) was significantly less than the force needed to secure the standard suture (2.17 +/- 0.58 kg) (P < 0.0001). Table 1 compares the suture pullout forces with the mesh failure forces. Although the pullout force for the standard suture is significantly greater than for the barbed suture, both sutures have a pullout strength significantly greater than the mesh failure force. Table 1 Suture fixation forces for standard and barbed sutures Suture fixation force (kg) Standard suture 2.17 +/- 0.58 Barbed suture 0.59 +/- 0.08 P < 0.0001 CONCLUSIONS: A barbed anchor suture used to secure mesh to the abdominal wall requires nearly 75% less strangulation force than a standard monofilament suture while still providing significantly greater pullout force than that required for the mesh to tear and fail. This method of mesh fixation should result in less postoperative pain and warrants a clinical trial. PMID- 22083329 TI - Sympathetic chain clipping for hyperhidrosis is not a reversible procedure. AB - BACKGROUND: Many techniques have been used to treat palmar hyperhidrosis. Compensatory sweating is a difficult adverse effect. Clipping has been proposed because of its supposed reversibility when clips are removed at a later date. The primary aims of this article are to investigate the neuronal lesion of the sympathetic chain caused by clipping and to study the possibility of regeneration after removal of the clips. METHODS: We performed an experimental study at the Minimally Invasive Surgery Centre Jesus Uson in Caceres (Spain). We used a swine model, performing clipping, unclipping, and extirpation of different segments of sympathetic chain with clips and after clip removal, following a chronogram of 10, 20, and 30 days. Pathologic studies of specimens and statistics were done at the University of Seville. RESULTS: Ten days after clipping, all sympathetic chains displayed evident Wallerian degeneration. Twenty days after clipping, Wallerian degeneration of myelinated fibers was more widespread and also more striking. Thirty days after clipping, a very marked macrophagic reaction was visible, with multiple signs of phagocytosis of myelin debris. By 30 days post operation and 20 days after clip removal, a few residual myelin and amyelinated fibers were visible. These findings suggest that axon regeneration is not possible. CONCLUSIONS: There are Wallerian degeneration and axon loss 10 days after clipping. The almost total absence of myelinated and amyelinated fibers following clip removal suggests that there was no nerve regeneration, and that therefore clipping cannot be considered a reversible technique. PMID- 22083328 TI - Laparoscopic versus open distal pancreatectomy: a systematic review of comparative studies. AB - INTRODUCTION: The laparoscopic approach to distal pancreatectomy (DP) for benign and malignant diseases appears to offer advantages and is replacing open surgery in some centers. This review examined the evidence from published data of comparative studies of laparoscopic versus open DP. METHODS: The Medline and PubMed databases were searched and relevant English language publications were systematically retrieved. Data were pooled by two independent reviewers. The results shown represent mean. RESULTS: Up to December 2010, 13 comparative studies of laparoscopic versus open DP were identified of which two were excluded, leaving 503 and 588 patients respectively for analysis. The conversion rate was 9.5%. The groups were comparable for age and sex, whilst open surgery was associated with significantly higher incidence of malignant pathology (20.1 vs. 15.0%) and larger tumors (3.9 vs. 3.5 cm) compared with laparoscopic surgery. There were no differences between the two approaches with regard to the operative time (220 vs. 208 min), rate of postoperative pancreatic fistula (16.1 vs. 19.5%), and mortality (0.6 vs. 0.5%). However, the laparoscopic approach was associated with significantly lower operative blood loss (237 vs. 562 ml), higher spleen preservation rate (37.8 vs. 8%), lower morbidity (30.5 vs. 38.4%), and shorter postoperative hospital stay (9.1 vs. 14.7 days). CONCLUSIONS: The laparoscopic approach to DP offers advantages over open surgery with lower operative morbidity, higher spleen preservation rate, and shorter hospital stay; these benefits are particularly observed in patients with benign disease and borderline malignancy. The experience with laparoscopic DP for malignant disease remains limited, and long-term follow-up data are required to clearly define this role. PMID- 22083330 TI - Laparoscopic ventral hernia repair: does primary repair in addition to placement of mesh decrease recurrence? AB - BACKGROUND: The advent of laparoscopic ventral hernia repair (LVHR) not only reduced the morbidity associated with open repair but also led to a decrease in the hernia recurrence rate. However, the rate continues to remain significant. METHODS: A retrospective observational study was conducted on 193 patients who were treated with LVHR by two minimally invasive surgeons in a 24-month period. The patient population was broadly divided into two groups based on the laparoscopic repair of the fascial defect with mesh underlay, or with primary suture repair and mesh underlay (PSR + MU). Patient demographics, rates of hernia recurrence, and other associated complications were compared between the two groups. Patient variables and the clinical outcomes were analyzed with descriptive statistics and chi-square test. RESULTS: One hundred ninety-three consecutive patients underwent LVHR for incisional (n = 136), umbilical (n = 44), epigastric (n = 9), and parastomal (n = 4) hernia. Hernia recurrence was documented in eight patients (4.1%). The mean follow-up period was 10.5 months (range 1-36 months). Incisional hernias accounted for all eight recurrences. The rate of recurrence in those treated with PSR + MU was 3% (two of 67 cases) in comparison with 4.8% (six of 126 patients) associated with mesh alone. The rate of recurrence in the recurrent hernia group, treated with mesh only, was 10.5% (four of 38 patients) compared with 4.8% (one of 21 patients) in the PSR + MU group. CONCLUSIONS: Primary laparoscopic repair along with mesh placement for the management of ventral hernia was found to be effective in selected cases as evidenced by the low rate of recurrence when compared with conventional laparoscopic repair with mesh alone. Further retrospective and prospective studies, with larger patient enrollment, are warranted to confirm the benefit of this technique over traditional repair. PMID- 22083331 TI - Intermediate results of a prospective randomized controlled trial of traditional four-port laparoscopic cholecystectomy versus single-incision laparoscopic cholecystectomy. AB - BACKGROUND: Minimally invasive techniques have become an integral part of general surgery, with recent investigation into single-incision laparoscopic cholecystectomy (SILC). This study presents a prospective, randomized, multicenter, single-blind trial of SILC compared with four-port cholecystectomy (4PLC) with the goal of assessing safety, feasibility, and factors predicting outcomes. METHODS: Patients with biliary colic and documented gallstones or polyps or with biliary dyskinesia were randomized to SILC or 4PLC. Data measures included operative details, adverse events, and conversion to 4PLC or laparotomy. Pain, cosmesis, and quality-of-life scores were documented. Patients were followed for 12 months. RESULTS: Two hundred patients were randomized to SILC (n = 117) or 4PLC (n = 80) (3 patients chose not to participate after randomization). Patients were similar except for body mass index (BMI), which was lower in the SILC patients (28.9 vs. 31.0, p = 0.011). One SILC patient required conversion to 4PLC. Operative time was longer for SILC (57 vs. 45 min, p < 0.0001), but outcomes, including total adverse events, were similar (34% vs. 38%, p = 0.55). Cosmesis scores favored SILC (p < 0.002), but pain scores were lower for 4PLC (1 point difference in 10-point scale, p < 0.028) despite equal analgesia use. Wound complications were greater after SILC (10% vs. 3%, p = 0.047), but hernia recurrence was equivalent for both procedures (1.3% vs. 3.4%, p = 0.65). Univariate analysis showed female gender, SILC, and younger age to be predictors for increased pain scores, while SILC was associated with improved cosmesis scores. CONCLUSIONS: In this multicenter randomized controlled trial of SILC versus 4PLC, SILC appears to be safe with a similar biliary complication profile. Pain scores and wound complication rates are higher for SILC; however, cosmesis scores favored SILC. For patients preferring a better cosmetic outcome and willing to accept possible increased postoperative pain, SILC offers a safe alternative to the standard 4PLC. Further follow-up is needed to detail the long term risk of wound morbidities, including hernia recurrence. PMID- 22083333 TI - Trainees' adenoma detection rate is higher if >= 10 minutes is spent on withdrawal during colonoscopy. AB - BACKGROUND: It has been demonstrated that prolonged colonoscopic withdrawal times (WT; >6 min) are beneficial for the adenoma detection rate (ADR) for experienced endoscopists. There are little data, however, to guide the appropriate colonoscopic withdrawal times for trainees. The purpose of this study was to determine whether there is a relationship between WTs and ADR for first-year fellows training in colonoscopy. METHODS: This is a prospective study of first year gastroenterology fellows at a single academic teaching hospital who documented each colonoscopy with a self-report form over the course of an academic year (March 2010 to February 2011). The internal policy for the trainees was to have at least a 6-min withdrawal time for each colonoscopy. RESULTS: Four first-year fellows in gastroenterology at an academic medical center completed self-reports for 1,210 colonoscopies. Mean WT was 10.2 +/- 3.4 min. The aggregate polyp detection rate was 33.2% and the aggregate ADR was 22.3%. For colonoscopies with WT < 10 min, ADR was 9.5%, and for colonoscopies with WT >= 10 min, ADR was 32.3% (p < 0.001). When the quality indicator of 25% goal ADR for males and 15% goal ADR for females is applied, this aggregate rate is achieved for both sexes for screening colonoscopies (n = 676) with WT >= 10 min. CONCLUSIONS: First-year trainees had a significantly higher ADR if their colonoscopic WT is >= 10 min. PMID- 22083332 TI - Testicular functions, chronic groin pain, and quality of life after laparoscopic and open mesh repair of inguinal hernia: a prospective randomized controlled trial. AB - BACKGROUND: Laparoscopic inguinal hernia repair is still not the gold standard for patients with inguinal hernia. The aim of this study was to compare testicular dysfunction, incidence and factors influencing chronic groin pain, and quality of life after laparoscopic and open mesh repair. METHODS: One hundred twenty patients were studied in a prospective randomized trial. One hundred seventeen patients completed the required follow-up, 60 following laparoscopic repair and 57 following open repair. Testicular functions were assessed by testicular volume, blood flow, and hormones, and quality of life was assessed with Short Form 36 version 2 preoperatively and postoperatively at 3 months. Pain was assessed at different time intervals preoperatively and postoperatively. RESULTS: Preoperative profiles of both groups were well matched. A significant decrease in testicular volume (p = 0.01) and less improvement in blood flow (p = 0.048) was seen after open repair. There was also a significant reduction in serum testosterone level (p = 0.02) with a significant increase in FSH and LH level (p < 0.001); however, there was no testicular atrophy. Incidence and severity of chronic groin pain were significantly less after laparoscopic repair during normal and strenuous activities, though they were similar to those after open repair during rest after 3 months postoperatively. Age, preoperative pain, pain at 1 week, and open repair were found to be independent risk factors for chronic pain on multivariate analysis. Quality of life was significantly better postoperatively in terms of physical functions, role physical, bodily pain, and general health after laparoscopic repair. CONCLUSION: Laparoscopic repair seems favorable in terms of better preservation of testicular functions, lower incidence of acute and chronic groin pain, and significant improvement in quality of life when compared to open repair. Younger age, preoperative pain, pain after 1 week postoperatively, and open mesh repair were found to be significant risk factors for chronic groin pain. PMID- 22083334 TI - Medical image analysis: computer-aided diagnosis of gastric cancer invasion on endoscopic images. AB - BACKGROUND: The aim of this study was to investigate the efficacy of diagnosing depth of wall invasion of gastric cancer on endoscopic images using computer aided pattern recognition. METHODS: The back propagation algorithm was used for computer training. Data of 344 patients who underwent gastrectomy or endoscopic tumor resection between 2001 and 2010 and their 902 endoscopic images were collected. The images were divided into ten groups among which the number of patients and images were almost equally distributed according to T staging. The computer learning was performed using about 800 images from all but one group, and the accuracy rate of diagnosing the depth of wall invasion of gastric cancer was calculated using the remaining group of about 90 images. The various numbers of input layers, hidden layers, and learning counts were updated, and the ideal setting was decided. Similar learning and diagnostic procedures were repeated ten times using every group and all 902 images were tested. The accuracy rate was calculated based on the ideal setting. RESULTS: The most appropriate setting was a resolution of 16 * 16, a hidden layer of 240, and a learning count of 50. In the next step, using all the images on the ideal setting, the overall accuracy rate was 64.7%. The diagnostic accuracy was 77.2, 49.1, 51.0, and 55.3% in the T1, T2, T3, and T4 stagings, respectively. The accuracy was 68.9% in T1a(M) staging and 63.6% in T1b(SM) staging. The positive predictive values were 80.1, 41.6, 51.4, and 55.8% in the T1, T2, T3, and T4 staging, respectively. It was 69.2% in T1a(M) staging and 68.3% in T1b(SM) staging. CONCLUSION: Computer-aided diagnosis is useful for diagnosing depth of wall invasion of gastric cancer on endoscopic images. PMID- 22083335 TI - A review of the role of GERD-induced aspiration after lung transplantation. AB - The increased prevalence of gastroesophageal reflux disease (GERD) in lung transplantation patients has been established; however, many questions persist regarding the relationship of GERD to aspiration and its potential to induce pulmonary allograft failure. Moreover, the biological implications of aspiration in lung transplantation have yet to be fully elucidated. The goal of this review was to assess the relationship between GERD and aspiration, focusing on the role of these events in the development of allograft injury after lung transplantation. PMID- 22083336 TI - Endoscopic ultrasound-guided endoscopic necrosectomy of the pancreas: is irrigation necessary? AB - BACKGROUND: Findings have shown endoscopic necrosectomy to be beneficial for patients with symptomatic pancreatic necrosis accessible for an endoscopic approach. The available studies show that endoscopic necrosectomy requires a multitude of subsequent procedures including repeat irrigation for removal of the necrotic material. This study aimed to investigate the need for additional irrigation in patients with necrotizing pancreatitis treated by endoscopic necrosectomy. METHODS: The study enrolled 35 consecutive patients (27 men) with a median age of 59 years who had pancreatic necrosis treated with endoscopic necrosectomy. Endoscopic ultrasound-guided internal drainage and consecutive endoscopic necrosectomy was combined with interval multistenting of the cavity. Neither endoscopic nor external irrigation was part of the procedure. RESULTS: An average of 6.2 endoscopy sessions per patient were needed for access, necrosectomy, and stent management. The in-hospital mortality rate was 6% (2/35), including one procedure-related death resulting from postinterventional aspiration. The immediate morbidity rate was 9% (3/35). It was possible to achieve clinical remission for all the surviving patients with no additional surgery needed for management of the necroses. The median follow-up period was 23 months. CONCLUSION: Neither endoscopic nor external flushing is needed for successful endoscopic treatment of symptomatic necroses. Even without irrigation, the outcome for patients treated with endoscopic necrosectomy is comparable to that described in the published data. PMID- 22083337 TI - Possible mortality reduction by endoscopic sphincterotomy during endoscopic retrograde cholangiopancreatography: a population-based case-control study. AB - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is widely used for young patients, but ERCP and endoscopic sphincterotomy in particular are reported to be associated with increased complication and mortality rates. This study aimed to calculate mortality and to identify risk factors for death within 90 days after ERCP for nonmalignant disease. METHODS: From the Swedish Hospital Discharge Registry, the authors identified all individuals in Stockholm County who had undergone in-patient ERCP during 1990-2003. Among these individuals, they excluded those recorded in the Swedish Cancer Registry as having a diagnosis of malignancy in the liver, pancreas, or bile ducts. Cases, defined as patients who had died within 90 days after the procedure, were identified by cross-linkage to the causes of death registry. Control subjects were randomly sampled from the same cohort. The medical records were studied to discern risk factors for death after ERCP. RESULTS: The mortality rate was 1.6%. Advanced age, severe comorbidity, high complexity of the procedure, and occurrence of a complication were associated with death within 90 days, whereas a previous cholecystectomy or the simultaneous performance of an endoscopic sphincterotomy reduced the risk. CONCLUSIONS: Old age and comorbidity are the main risk factors for death after ERCP, but a complex procedure or the occurrence of a complication also seems to increase short-term mortality. The performance of a sphincterotomy may reduce the risk of death, possibly by facilitating adequate drainage. A previous cholecystectomy also may decrease the risk of death after ERCP. PMID- 22083338 TI - Robot-assisted total gastrectomy is comparable with laparoscopically assisted total gastrectomy for early gastric cancer. AB - BACKGROUND: Laparoscopically assisted total gastrectomy (LATG) is technically difficult. Robot surgery has theoretical advantages such as increased degrees of freedom of instruments and a three-dimensional view. The current study aimed to determine whether a robot-assisted total gastrectomy (RATG) has a real benefit over LATG in terms of surgical and oncologic outcomes. METHODS: A single-center case-control study was conducted. The study included 36 patients who underwent RATG and 65 patients who underwent LATG at the National Cancer Center in Korea between February 2009 and May 2011. No patients were excluded from the analysis within the study period. Clinicopathologic data, operative data, postoperative morbidity, and pathologic data were analyzed by Student's t-tests and Chi-square tests, as indicated. RESULTS: The mean age of the patients was 53.9 +/- 11.7 years in the RATG group and 56.9 +/- 12.3 years in the LATG group (P = 0.236). The mean BMI was 23.2 +/- 2.5 kg/m(2) in the RATG group and 23.6 +/- 3.4 kg/m(2) in the LATG group (P = 0.494). The mean postoperative hospital stay was 8.8 +/- 3.3 days in the RATG group and 10.3 +/- 10.8 days in the LATG group (P = 0.416). The mean operative time was 305.8 +/- 115.8 min in the RATG group and 210.2 +/- 57.7 min in the LATG group (P < 0.001). The mean number of dissected lymph nodes was 42.8 +/- 12.7 in the RATG group and 39.4 +/- 13.4 in the LATG group (P = 0.209). Postoperative complications were experienced by 6 patients (16.7%) in the RATG group and 10 patients (15.4%) in the LATG group (P = 0.866). CONCLUSION: Despite early experiences, RATG was shown to be comparable with LATG in terms of surgical and oncologic outcomes. However, no apparent benefit is associated with RATG to date. PMID- 22083339 TI - The safety of biologic mesh for laparoscopic repair of large, complicated hiatal hernia. AB - BACKGROUND: Biologic mesh is widely used for repair of large, complicated hiatal hernias. Recently, there have been reports of complications after its implantation. We studied the course of a large group of patients who had undergone hiatal hernia repair with use of biologic mesh to determine the rate of immediate and late complications related to its use. METHODS: All patients who had biologic mesh placed at the hiatus and who had been followed for at least 1 year were included. Perioperative data were reviewed, and a questionnaire was administered, designed to identify symptoms of gastroesophageal reflux, other symptoms such as dysphagia, and all other operative or endoscopic interventions that occurred after mesh implantation. In addition, postoperative radiologic and endoscopic studies were reviewed to assess signs of complications related to use of mesh. RESULTS: There were 126 patients eligible for the study. We were able to contact 73 of these patients, at median follow-up of 45 months. No mesh-related complications were found. The frequency and severity of heartburn, regurgitation, and dysphagia improved significantly compared with preoperative values, and 89% of the patients reported good to excellent results in terms of overall satisfaction. Six patients recorded worsening of dysphagia postoperatively, but after careful work-up and review of each individual case, no case seemed to be directly related to the mesh. No erosions, strictures, or other complications directly related to use of mesh were found. One patient required reoperation due to hiatal hernia recurrence with gastroesophageal reflux disease (GERD) symptoms. CONCLUSIONS: Use of biologic mesh for laparoscopic repair of large, complicated hiatal hernias appears safe. There were no major complications related to the mesh, and overall satisfaction with the operation was very good. PMID- 22083341 TI - Measuring sensitivity to conflicts of interest: a preliminary test of method. AB - This study presents and develops test methods for assessing sensitivity to conflict of interest (COIsen). We are aware of no study assessing COIsen, but note that some popular methods for assessing ethical sensitivity and related constructs (which include COIsen) are flawed in that their presentation of stimulus material to subjects actually guides subjects to attend to ethical (or related) issues. The method tested here was designed to avoid this flaw. Using adaptations of two existing cases, a quota sample of 12 students was interviewed. Our method used funnel-sequenced, open-ended interviews that were audiotaped and transcribed, then subjected to a form of cognitive mapping. These maps revealed the presence of "indicators" of COIsen. We found that COIsen can be measured and that the global COIsen score generated by our method is able to reveal much variation across subjects, making it a worthwhile candidate for further consideration. PMID- 22083340 TI - Three new sensitive and specific heat-shock protein 70 PCRs for global Leishmania species identification. AB - The heat-shock protein 70 gene (hsp70) has been exploited for Leishmania species identification in the New and Old World, using PCR followed by restriction fragment length polymorphism (RFLP) analysis. Current PCR presents limitations in terms of sensitivity, which hampers its use for analyzing clinical and biological samples, and specificity, which makes it inappropriate to discriminate between Leishmania and other trypanosomatids. The aim of the study was to improve the sensitivity and specificity of a previously reported hsp70 PCR using alternative PCR primers and RFLPs. Following in silico analysis of available sequences, three new PCR primer sets and restriction digest schemes were tested on a globally representative panel of 114 Leishmania strains, various other infectious agents, and clinical samples. The largest new PCR fragment retained the discriminatory power from RFLP, while two smaller fragments discriminated less species. The detection limit of the new PCRs was between 0.05 and 0.5 parasite genomes, they amplified clinical samples more efficiently, and were Leishmania specific. We succeeded in significantly improving the specificity and sensitivity of the PCRs for hsp70 Leishmania species typing. The improved PCR-RFLP assays can impact diagnosis, treatment, and epidemiological studies of leishmaniasis in any setting worldwide. PMID- 22083342 TI - Arsenic toxicity in a sediment-dwelling polychaete: detoxification and arsenic metabolism. AB - The accumulation, subcellular distribution and speciation of arsenic in the polychaete Arenicola marina were investigated under different laboratory exposure conditions representing a range of metal bioavailabilities, to gain an insight into the physiological mechanisms of how A. marina handles bioaccumulated arsenic and to improve our understanding of the potential ecotoxicological significance of bioaccumulated arsenic in this deposit-feeder. The exposure conditions included exposure to sublethal concentrations of dissolved arsenate, exposure to sublethal concentrations of sediment-bound metal mining mixtures, and exposure to lethal concentrations of sediment-bound metal mining mixtures and arsenic- and multiple metal-spiked sediments. The sub-lethal exposures indicate that arsenic bioaccumulated by the deposit-feeding polychaete A. marina is stored in the cytosol as heat stable proteins (~50%) including metallothioneins, possibly as As (III)-thiol complexes. The remaining arsenic is mainly accumulated in the fraction containing cellular debris (~20%), with decreasing proportions accumulated in the metal-rich granules, organelles and heat-sensitive proteins fractions. A biological detoxified metal compartment including heat stable proteins and the fraction containing metal-rich granules is capable of binding arsenic coming into the cells at a constant rate under sublethal arsenic bioavailabilities. The remaining arsenic entering the cell is bound loosely into the cellular debris fraction, which can be subsequently released and diverted to an expanding detoxified pool. Our results suggest that a metal sensitive compartment comprising the cellular debris, enzymes and organelles fractions may be more representative of the toxic effects observed. PMID- 22083343 TI - Labelling of granulocytes by phagocytic engulfment with 64Cu-labelled chitosan coated magnetic nanoparticles. AB - PURPOSE: The aim of the present work was to perform the labelling of granulocytes by their engulfment with chitosan-coated magnetic (64)Cu nanoparticles (MNPs) in order to obtain a radiopharmaceutical suitable for dual imaging (PET-MRI) of inflammatory/infective diseases. PROCEDURES: Specimens of 5-20 mg MNPs were washed with saline-isotonic solution and recuperated by magnetic decantation; 15 58 MUg Cu(2+) (CuCl(2).H(2)O) in 50 MUl of acidified (pH 5.5) saline solution was added to the MNPs re-suspended saline-isotonic solution; 10 mg MNPs was allowed to react with 16 MUg (64)Cu [(64)Ni(p,n) at 12-9 MeV] followed by anion exchange chromatography with a specific activity of 56 MBq/MUg. Pellets of granulocytes were obtained from peripheral blood; MNPs engulfment by granulocytes was obtained and granulocyte-engulfed viability was assessed by the trypan blue exclusion (TBE) test performed at 5 min, 2 h and 4 h; assessment of the release of (64)Cu from labelled granulocytes in plasma was performed by measuring the radioactivity of both the cellular pellet and the supernatant solution. RESULTS: Our data showed the binding capacity of chitosan-coated MNPs for cationic metal. The amount of Cu(+2) chelated captured per milligram of MNPs was constant and independent of the reagent concentrations. In all cases, more than 90% of the engulfed granulocytes were positive to the TBE test. The MNPs were localised within the cells. CONCLUSION: In our in vitro model, MNPs are taken up by granulocytes through phagocytosis, whereas previously described methods were based on the use of a chelating agent that permit Cu to cross the cell membrane. Moreover, the (64)Cu-engulfed granulocytes showed a high stability of up to 80% of retained radioactivity after 24 h of incubation. PMID- 22083344 TI - Discrimination, family relationships, and major depression among Asian Americans. AB - Depression represents a growing concern among Asian Americans. This study examined whether discrimination and family dynamics are associated with depression in this population. Weighted logistic regressions using nationally representative data on Asian American adults (N = 2095) were used to examine associations between discrimination, negative interactions with relatives, family support, and 12-month major depressive disorder (MDD). Discrimination (odds ratio [OR] = 2.13, 95% confidence interval [CI] = 1.67, 2.71) and negative interactions with relatives (OR = 1.28, 95% CI = 1.03, 1.58) were positively associated with MDD. Family support was associated with lower MDD (OR = 0.73, 95% CI = 0.59, 0.89), and buffered lower levels of discrimination. Results suggest that discrimination may have negative mental health implications, and also point to the importance of family relationships for depression among Asian Americans. Findings suggest that providers may consider stress experienced at multiple ecological levels to address Asian American mental health needs. PMID- 22083346 TI - MicroRNA regulation in cancer-associated fibroblasts. AB - The microenvironment of cancer cells has proven to be a critical component of tumors that strongly influences cancer development and progression into invasive and metastatic disease. Compared to normal tissue, dramatic differences in gene expression occur in multiple cell types that constitute the tumor microenvironment including cancer-associated fibroblasts (CAFs) that are important stromal components of growing tumors. In this review, we present recent advances in understanding how microRNAs are deregulated in cancer-associated fibroblasts (CAFs) and how this affects tumor biology. The microRNA signature of CAFs is discussed with respect to their functional relevance to tumor cells as well as other cell types involved in tumor homeostasis. PMID- 22083345 TI - Immunotherapy with IL-10- and IFN-gamma-producing CD4 effector cells modulate "Natural" and "Inducible" CD4 TReg cell subpopulation levels: observations in four cases of patients with ovarian cancer. AB - Adoptive T cell therapy for cancer patients optimally requires participation of CD4 T cells. In this phase I/II study, we assessed the therapeutic effects of adoptively transferred IL-10- and IFN-gamma-producing CD4 effector cells in patients with recurrent ovarian cancer. Using MUC1 peptide and IL-2 for ex vivo CD4 effector cell generation, we show that three monthly treatment cycles of autologous T cell restimulation and local intraperitoneal re-infusion-modulated T cell-mediated immune responses that were associated with enhanced patient survival. One patient remains disease-free, another patient experienced prolonged survival for nearly 16 months with recurrent disease, and two patients expired within 3-5 months following final infusion. Prolonged survivors showed elevated levels of systemic CD3(+)CD4(+)CD25(+) and CD3(+)CD4(+)CD25(-) T cells when compared to that of pre-treatment levels and similarly treated short-term survivors. Such cell populations among these patients contained variable levels of "Inducible" Tr1 (CD4(+)CD25(-)FoxP3(-)IL-10(+)) and "Natural" (CD4(+)CD25(+)CD45RO(+)FoxP3(+)) TReg cell numbers and ratios that were associated with prolonged and/or disease-free survival. Moreover, peptide restimulated T cells from these patients showed an elevation in both IFN-gamma production, memory cell phenotype, and select TNF family ligands associated with enhanced T cell survival and apoptosis-inducing activities. This suggests that intraperitoneally administered Th1-like cells, producing elevated levels of IL 10, may require and/or induce differential levels of distinct systemic TReg subpopulations that influence, in part, long-term tumor immunity and enhanced memory/effector CD4-mediated therapeutic potentials. Furthermore, treatment efficacy and enhanced memory cell phenotype did not appear to be dependent on TReg cell numbers but upon ratios of "Inducible" and "Natural" TReg subpopulations. PMID- 22083347 TI - Calreticulin as a potential diagnostic biomarker for lung cancer. AB - Calreticulin (CRT) is an endoplasmic reticulum luminal Ca(2+)-binding chaperone protein. By immunizing mice with recombinant fragment (rCRT/39-272), six clones of monoclonal antibodies (mAbs) were generated and characterized. Based on these mAbs, a microplate chemiluminescent enzyme immunoassay (CLEIA) system with a measured limit of detection of 0.09 ng/ml was developed. Using this CLEIA system, it was found that soluble CRT (sCRT) level in serum samples from 58 lung cancer patients was significantly higher than that from 40 healthy individuals (only 9 were detectable, P < 0.0001). Among them, serum sCRT in the small cell lung cancer was lower than that in adenocarcinoma (P = 0.0085), while both were lower than that in the squamous cell carcinoma (P = 0.013, P = 0.0012, respectively). Moreover, it was found that sCRT in sera from the patients after chemotherapy was higher than that from the patients without chemotherapy (P = 0.042). Further study by immunohistochemistry showed that CRT was also highly expressed in the cytoplasm and on the membrane of the lung cancer cells, while there was a trace amount of CRT expression in normal lung cells. Correspondingly, the expression level of CRT on lung cancer cell membrane was associated with the tumor pathological grade. This study demonstrates that sCRT concentration in sera of lung cancer patients is higher than that in sera of healthy individuals, and CRT expression level on lung cancer cell membrane is associated with tumor pathological classification and grade. These findings suggest that CRT may be used as a biomarker in lung cancer prediction and diagnosis. PMID- 22083348 TI - [Certification of colorectal cancer units -- a critical overview on the basis of unsettled aspects]. AB - In this contribution the rational of colorectal cancer centre certification is discussed on the basis of previously published literature and several unsettled factors which are not yet considered as influencing the quality of cancer treatment. The representation of the theme cannot be comprehensive or complete. The readers should be stimulated by one or the other topic to reach their own critical assessment. Due to several limitations of the published literature and the various unsettled aspects, the purpose of colorectal cancer centre certification is called into question. PMID- 22083349 TI - [Left renal vein - optional collateral damage in aortic aneurysm surgery?]. PMID- 22083350 TI - [Anorectal melanoma--a retrospective analysis of seven cases]. PMID- 22083351 TI - A genomic approach to predict synergistic combinations for breast cancer treatment. AB - We leverage genomic and biochemical data to identify synergistic drug regimens for breast cancer. In order to study the mechanism of the histone deacetylase (HDAC) inhibitors valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) in breast cancer, we generated and validated genomic profiles of drug response using a series of breast cancer cell lines sensitive to each drug. These genomic profiles were then used to model drug response in human breast tumors and show significant correlation between VPA and SAHA response profiles in multiple breast tumor data sets, highlighting their similar mechanism of action. The genes deregulated by VPA and SAHA converge on the cell cycle pathway (Bayes factor 5.21 and 5.94, respectively; P-value 10(-8.6) and 10(-9), respectively). In particular, VPA and SAHA upregulate key cyclin-dependent kinase (CDK) inhibitors. In two independent datasets, cancer cells treated with CDK inhibitors have similar gene expression profile changes to the cellular response to HDAC inhibitors. Together, these results led us to hypothesize that VPA and SAHA may interact synergistically with CDK inhibitors such as PD-033299. Experiments show that HDAC and CDK inhibitors have statistically significant synergy in both breast cancer cell lines and primary 3-dimensional cultures of cells from pleural effusions of patients. Therefore, synergistic relationships between HDAC and CDK inhibitors may provide an effective combinatorial regimen for breast cancer. Importantly, these studies provide an example of how genomic analysis of drug response profiles can be used to design rational drug combinations for cancer treatment. PMID- 22083352 TI - In situ controlled growth of well-dispersed gold nanoparticles in TiO2 nanotube arrays as recyclable substrates for surface-enhanced Raman scattering. AB - In this paper, well-aligned Au-decorated TiO(2) nanotube arrays with high surface enhanced Raman scattering (SERS) enhancement were prepared using a facile in situ reduction and controlled growth approach. The gold nanoparticles are well dispersed and assembled on the mouth surface and the inside of the TiO(2) nanotubes without clogging. The structure and optical properties of the Au decorated TiO(2) nanotube arrays have been characterized. The Au-decorated TiO(2) nanotube arrays were employed as SERS-active substrates, which exhibit good performance due to long-range coupling between Au nanoparticles, and TiO(2) assisted enhanced charge-transfer from Au to Rh6G. The SERS activity of the substrates strongly depends on the crystallite size and level of aggregation. The substrates display significant fluorescence quenching ability and uniform SERS responses throughout the whole surface area. Particularly, good recyclability is shown. The photocatalytic property of Au-decorated TiO(2) nanotube array was exploited to recycle the substrate through UV light photocatalytic purification. The experimental results showed that the substrate is featured by high reproducibility and can be used as a highly efficient SERS substrate for multiple detection of different chemical and biological molecules. PMID- 22083353 TI - Enantioselective organocatalytic fluorination using organofluoro nucleophiles. AB - Synthetic fluorinated compounds are enormously useful in areas such as materials, agrochemicals, pharmaceuticals and fine chemicals. While methods of electrophilic fluorination have been extensively developed to stereoselectively install fluorine atoms onto molecules, nucleophilic fluorination is a much less explored approach. Recently, several organofluoro reagents have been designed and used as nucleophiles in the asymmetric synthesis of fluorinated compounds, significantly expanding the scope of enantio-enriched fluorine-containing compounds that can be synthesised. Such organofluoro nucleophiles are particularly useful in organocatalytic transformations. In this review, recent advances in the application of organofluoro nucleophiles in organocatalysis are summarised. PMID- 22083354 TI - Molecular sequence variations of the lipoxygenase-2 gene in soybean. AB - Soybean lipoxygenase genes comprise a multi-gene family, with the seed lipoxygenase isozymes LOX1, LOX2, and LOX3 present in soybean seeds. Among these, the LOX2 isozyme is primarily responsible for the "beany" flavor of most soybean seeds. The variety, Jinpumkong 2, having null alleles (lx1, lx2, and lx3) lacks the three seed lipoxygenases; so, sequence variations between the lipoxygenase-2 genes of Pureunkong (Lx2) and Jinpumkong 2 (lx2) cultivars were examined. One indel, four single nucleotide polymorphisms (SNPs), a 175-bp fragment in the 5' flanking sequence, and a missense mutation within the coding region were found in Jinpumkong 2. The distribution of the sequence variations was investigated among 90 recombinant inbred lines (RILs) derived from a cross of Pureunkong * Jinpumkong 2 and in 480 germplasm accessions with various origins and maturity groups. Evidence for a genetic bottleneck was observed: the 175-bp fragment was rare in Glycine max, but present in the majority of the G. soja accessions. Furthermore, the 175-bp fragment was not detected in the 5' upstream region of the Lx2 gene on chromosome (Chr) 13 in Williams 82; instead, a similar 175-bp fragment was positioned in the homeologous region on Chr 15. The findings indicated that the novel fragment identified was originally present in the Lx2 region prior to the recent genome duplication in soybean, but became rare in the G. max gene pool. The missense mutation of the conserved histidine residue of the lx2 allele was developed into a single nucleotide-amplified polymorphism (SNAP) marker. The missense mutation showed a perfect correlation with the LOX2-lacking phenotype, so the SNAP marker is expected to facilitate breeding of soybean cultivars which lack the LOX2 isozyme. PMID- 22083355 TI - Intron-length polymorphism identifies a Y2K4 dehydrin variant linked to superior freezing tolerance in alfalfa. AB - Breeding alfalfa (Medicago sativa L.) with superior freezing tolerance could be accelerated by the identification of molecular markers associated to that trait. Dehydrins are a group of highly hydrophilic proteins that have been related to low temperature tolerance. We previously identified a dehydrin restriction fragment length polymorphism (RFLP) among populations recurrently selected for superior tolerance to freezing (TF). Analysis of crosses between genotypes with (D+) or without (D-) that RFLP revealed a significant impact on freezing tolerance. In this study, we sought to develop a PCR marker for freezing tolerance based on prior evidence of a relationship between size variation in Y(2)K(4) dehydrins and the RFLP. Results confirm the enrichment of Y(2)K(4) sequences of intermediate size (G2 group) in response to recurrent selection and in the D+ progeny. Analysis of genomic sequences revealed significant intron length polymorphism (ILP) within the G2 group. G2 sequences with a characteristic short intron were more frequently found in D+ genotypes. Amplification using sequence-characterized amplified region (SCAR) primers bordering the intron confirmed an increase in the number of fragments with small introns in the D+ progeny and in the ATF5 population obtained after five cycles of recurrent selection for superior TF within the cultivar Apica (ATF0). Conversely, there was a reduction in the number of fragments with long introns in the D+ progeny and in ATF5 as compared to ATF0. Recurrent selection for superior tolerance to freezing in combination with ILP identified a sequence variant of Y(2)K(4) dehydrins associated to the phenotypic response to selection. PMID- 22083356 TI - Identifying novel QTLs for submergence tolerance in rice cultivars IR72 and Madabaru. AB - Short-term submergence is a recurring problem in many rice production areas. The SUB1 gene, derived from the tolerant variety FR13A, has been transferred to a number of widely grown varieties, allowing them to withstand complete submergence for up to 2 weeks. However, in areas where longer-term submergence occurs, improved varieties having higher tolerance levels are needed. To search for novel quantitative trait loci (QTLs) from other donors, an F(2:3) population between IR72 and Madabaru, both moderately tolerant varieties, was investigated. After a repeated phenotyping of 466 families under submergence stress, a subset of 80 families selected from the two extreme phenotypic tails was used for the QTL analysis. Phenotypic data showed transgressive segregation, with several families having an even higher survival rate than the FR13A-derived tolerant check (IR40931). Four QTLs were identified on chromosomes 1, 2, 9, and 12; the largest QTL on chromosome 1 had a LOD score of 11.2 and R (2) of 52.3%. A QTL mapping to the SUB1 region on chromosome 9, with a LOD score of 3.6 and R (2) of 18.6%, had the tolerant allele from Madabaru, while the other three QTLs had tolerant alleles from IR72. The identification of three non-SUB1 QTLs from IR72 suggests that an alternative pathway may be present in this variety that is independent of the ethylene-dependent pathway mediated by the SUB1A gene. These novel QTLs can be combined with SUB1 using marker assisted backcrossing in an effort to enhance the level of submergence tolerance for flood-prone areas. PMID- 22083357 TI - Feasibility of three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging as a prognostic factor in patients with sudden hearing loss. AB - The aim of this study was to confirm the feasibility of high signal on three dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D FLAIR MRI) as one of the prognostic factors in recovery of sudden idiopathic hearing loss. A retrospective study was conducted using patients who were diagnosed with unilateral sudden idiopathic hearing loss from January 2008 to December 2010. A total of 120 patients were enrolled in for this study. High intensity signal in the inner ear on precontrast 3D FLAIR MRI was observed in 31 patients (25.8%; FHS) and labyrinthine enhancement was not observed in another 89 patients (FNS; 74.2%). There was no significant difference in patients' characteristics between two groups except final hearing. Final puretone average of the FHS group was 49.4 dB, significantly worse than FNS group's 36.7 dB (p = 0.037 < 0.05). Final hearing was related to initial hearing, accompanying dizziness, and abnormal auditory brainstem response result by multiple regression analysis. However, presence of high-intensity signal on precontrast 3D FLAIR MRI did not affect final hearing significantly. Significant difference due to the presence of dizziness in final hearing was observed in whole patients and in the FHS group, whereas no significant difference in final hearing was observed in FNS group. (p = 0.063 > 0.05). From these findings, the presence of high-intensity signal on 3D FLAIR MRI is a subfactor related to dizziness rather than a single poor prognostic factor and the absence of high-intensity signal on 3D FLAIR MRI can possibly imply relative good prognosis. PMID- 22083358 TI - The relationship between Bell's palsy and morphometric aspects of the facial nerve. AB - Epidemiological data of Bell's palsy (BP) have been reported. For example, the annual incidence of BP is 15-30 per 100,000 persons, with equal numbers of men and women affected, and there is no predilection for either side of the face. However, details of the relationship between BP and morphometric aspects of the facial nerve have not been available in textbooks. We performed a morphometric analysis of human facial nerve fibers and estimated the total number of myelinated axons (TN) and average transverse area of myelinated axons (ATA). The facial nerve showed a significant decrease of TN with increasing age (r = -0.77; p < 0.01), but showed no significant changes of ATA with age (r = -0.01; p = 0.96). We supposed that the TN decrease with age was a factor in the delayed recovery from BP seen in the elderly. Moreover, the TN and ATA showed no significant differences between female and male specimens (p < 0.05), or between the right and left side specimens (p < 0.05). Our present results seem to explain the absence of significant sex and affected side differences in BP. PMID- 22083360 TI - Assessing somatic hypermutation in Ramos B cells after overexpression or knockdown of specific genes. AB - B cells start their life with low affinity antibodies generated by V(D)J recombination. However, upon detecting a pathogen, the variable (V) region of an immunoglobulin (Ig) gene is mutated approximately 100,000-fold more than the rest of the genome through somatic hypermutation (SHM), resulting in high affinity antibodies. In addition, class switch recombination (CSR) produces antibodies with different effector functions depending on the kind of immune response that is needed for a particular pathogen. Both CSR and SHM are initiated by activation induced cytidine deaminase (AID), which deaminates cytosine residues in DNA to produce uracils. These uracils are processed by error-prone forms of repair pathways, eventually leading to mutations and recombination. Our current understanding of the molecular details of SHM and CSR come from a combination of studies in mice, primary cells, cell lines, and cell-free experiments. Mouse models remain the gold standard with genetic knockouts showing critical roles for many repair factors (e.g. Ung, Msh2, Msh6, Exo1, and polymerase eta). However, not all genes are amenable for knockout studies. For example, knockouts of several double-strand break repair proteins are embryonically lethal or impair B cell development. Moreover, sometimes the specific function of a protein in SHM or CSR may be masked by more global defects caused by the knockout. In addition, since experiments in mice can be lengthy, altering expression of individual genes in cell lines has become an increasingly popular first step to identifying and characterizing candidate genes. Ramos - a Burkitt lymphoma cell line that constitutively undergoes SHM - has been a popular cell-line model to study SHM. One advantage of Ramos cells is that they have a built-in convenient semi quantitative measure of SHM. Wild type cells express IgM and, as they pick up mutations, some of the mutations knock out IgM expression. Therefore, assaying IgM loss by fluorescence-activated cell scanning (FACS) provides a quick read-out for the level of SHM. A more quantitative measurement of SHM can be obtained by directly sequencing the antibody genes. Since Ramos cells are difficult to transfect, we produce stable derivatives that have increased or lowered expression of an individual gene by infecting cells with retroviral or lentiviral constructs that contain either an overexpression cassette or a short hairpin RNA (shRNA), respectively. Here, we describe how we infect Ramos cells and then use these cells to investigate the role of specific genes on SHM (Figure 1). PMID- 22083361 TI - Does lengthening and then plating (LAP) shorten duration of external fixation? AB - BACKGROUND: Classic bone lengthening requires patients wear external fixation for the distraction and consolidation phases and there is fracture risk after frame removal. Our technique of lengthening with the Taylor Spatial Frame(TM) and then insertion of a locked plate allows earlier removal of the external fixator during consolidation. Plate insertion is accomplished through a clean pin-free zone avoiding contamination and before frame removal maintaining bone position. QUESTIONS/PURPOSES: We asked (1) whether lengthening and then plating (LAP) decrease the time for external fixation (2) how alignment and complications compare with those of the classic method. METHODS: We performed a retrospective case-matched comparison between LAP and the classic technique with 27 extremities in each group. We compared time wearing the frame, bone healing index, external fixation index, joint ROM, alignment, and complications. RESULTS: The time wearing the frame and external fixation index were lower in the LAP group (4.5 versus 6.2 months and 1.5 versus 2 months/cm). Deviation from normal alignment was observed in seven and six patients in the LAP and classic group, respectively. Varus malalignment in two patients in the LAP group was associated with plate breakage. The incidence of pin-tract infection was greater in the classic group (12 versus two). No deep infections occurred in the LAP group. CONCLUSIONS: The LAP technique shortened the time patients wore the external fixator but was associated with a high incidence of varus deformity. Stronger plates may help prevent deformity and allow earlier removal of the frame. LEVEL OF EVIDENCE: Level III, therapeutic study (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22083362 TI - Hyperkalaemia in a female patient with systemic lupus erythematosus. PMID- 22083364 TI - Henoch-Schonlein nephritis with nephrotic state in children: predictors of poor outcomes. PMID- 22083365 TI - Molecular Adsorbents Recirculating System dialysis in children with cholestatic pruritus. AB - BACKGROUND: Cholestatic pruritus may severely compromise quality of life. The Molecular Adsorbents Recirculating System (MARS) allows removal of pruritogenic substances without exposure to foreign proteins. Pediatric data, however, are scant. METHODS: We retrospectively analyzed the efficacy of MARS in three boys with severe cholestatic pruritus. They received a total of 135 MARS sessions during 8, 4, and 13 months prior to liver transplantation. Total serum bilirubin and bile acids were monitored, and pruritus was assessed by a numerical rating scale (NRS 0 = no pruritus, 10 = maximal pruritus). RESULTS: MARS sessions were initially performed three times weekly at a mean duration of 6.3 +/- 1.4 h. Sessions could be reduced to once weekly and once every other week in two patients. Pre-MARS plasma bile acid concentrations averaged 207 +/- 67 MUmol/l. They declined to 67 +/- 9%, 48 +/- 3%, 38 +/- 14%, and 37 +/- 5% of baseline within 2, 4, 6 and 8 h of therapy, respectively (all p < 0.05). The average interdialytic increase of plasma bile acids was 34 +/- 33 MUmol/l per day. Mean NRS score decreased from 6.5 +/- 2.3 to 3.3 +/- 2.9 (p < 0.01). Skin lesions from itching disappeared. All MARS treatments were well tolerated. CONCLUSION: MARS dialysis substantially reduces cholestatic pruritus in children refractory to pharmacological treatment. PMID- 22083366 TI - Individually customised fetal weight charts derived from ultrasound measurements: the Generation R Study. AB - Maternal and fetal characteristics are important determinants of fetal growth potential, and should ideally be taken into consideration when evaluating fetal growth variation. We developed a model for individually customised growth charts for estimated fetal weight, which takes into account physiological maternal and fetal characteristics known at the start of pregnancy. We used fetal ultrasound data of 8,162 pregnant women participating in the Generation R Study, a prospective, population-based cohort study from early pregnancy onwards. A repeated measurements regression model was constructed, using backward selection procedures for identifying relevant maternal and fetal characteristics. The final model for estimating expected fetal weight included gestational age, fetal sex, parity, ethnicity, maternal age, height and weight. Using this model, we developed individually customised growth charts, and their corresponding standard deviations, for fetal weight from 18 weeks onwards. Of the total of 495 fetuses who were classified as small size for gestational age (<10th percentile) when fetal weight was evaluated using the normal population growth chart, 80 (16%) were in the normal range when individually customised growth charts were used. 550 fetuses were classified as small size for gestational age using individually customised growth charts, and 135 of them (25%) were classified as normal if the unadjusted reference chart was used. In conclusion, this is the first study using ultrasound measurements in a large population-based study to fit a model to construct individually customised growth charts, taking into account physiological maternal and fetal characteristics. These charts might be useful for use in epidemiological studies and in clinical practice. PMID- 22083368 TI - Development of a minimally invasive laser needle system: effects on cortical bone of osteoporotic mice. AB - Many studies have shown the positive effects of low-level laser therapy in the treatment of bone disease. However, laser radiation is scattered in the skin surface which reduces the initial photon density for tissue penetration and consequently the therapeutic efficacy. We developed a minimally invasive laser needle system (MILNS) to avoid laser scattering in tissue and investigated its stimulatory effects in the cortical bone of osteoporotic mice. The MILNS was designed to stimulate cortical bone directly by employing fine hollow needles to guide 100 MUm optical fibers. The study animals comprised 12 mice which were subjected to sciatic denervation of the right hind limb and were randomly divided into two groups, a sham group and a laser group which were treated using the MILNS for 2 weeks without and with laser irradiation, respectively. In vivo micro CT images were taken to analyze the structural parameters and bone mineral density. After 2 weeks of treatment with the MILNS, the relative changes in mean polar moment inertia, cross-section thickness, and periosteal perimeter were significantly higher in the laser group than in the sham group. Moreover, the distribution of bone mineral density index was higher in the laser group. The MILNS was developed as a minimally invasive treatment modality for bone disease and resulted in positive therapeutic efficacy in the cortical bone of osteoporotic mice. PMID- 22083369 TI - RFID sensor-tags feeding a context-aware rule-based healthcare monitoring system. AB - Along with the growing of the aging population and the necessity of efficient wellness systems, there is a mounting demand for new technological solutions able to support remote and proactive healthcare. An answer to this need could be provided by the joint use of the emerging Radio Frequency Identification (RFID) technologies and advanced software choices. This paper presents a proposal for a context-aware infrastructure for ubiquitous and pervasive monitoring of heterogeneous healthcare-related scenarios, fed by RFID-based wireless sensors nodes. The software framework is based on a general purpose architecture exploiting three key implementation choices: ontology representation, multi-agent paradigm and rule-based logic. From the hardware point of view, the sensing and gathering of context-data is demanded to a new Enhanced RFID Sensor-Tag. This new device, de facto, makes possible the easy integration between RFID and generic sensors, guaranteeing flexibility and preserving the benefits in terms of simplicity of use and low cost of UHF RFID technology. The system is very efficient and versatile and its customization to new scenarios requires a very reduced effort, substantially limited to the update/extension of the ontology codification. Its effectiveness is demonstrated by reporting both customization effort and performance results obtained from validation in two different healthcare monitoring contexts. PMID- 22083370 TI - Implement the RFID position based system of automatic tablets packaging machine for patient safety. AB - Patient safety has been regarded as the most important quality policy of hospital management. The medicine dispensing definitely plays an influential role in the Joint Commission International Accreditation Standards. The problem we are going to discuss in this paper is that the function of detecting mistakes does not exist in the Automatic Tablets packaging machine (ATPM) in the hospital pharmacy department when the pharmacists implement the replenishment of cassettes. In this situation, there are higher possibilities of placing the wrong cassettes back to the wrong positions, so that the human errors will lead to a crucial impact on total inpatients undoubtedly. Therefore, this study aims to design the RFID (Radio frequency identification) position based system (PBS) for the ATPM with passive high frequency (HF) model. At first, we placed the HF tags on each cassette and installed the HF readers on the cabinets for each position. Then, the system works on the reading loop to verify ID numbers and positions on each cassette. Next, the system would detect whether the orbit opens or not and controls the readers' working power consumption for drug storage temperature. Finally, we use the RFID PBS of the ATPM to achieve the goal of avoiding the medication errors at any time for patient safety. PMID- 22083372 TI - Indications and outcome of abdominal myomectomy in University of Maiduguri Teaching Hospital: Review of ten year. AB - BACKGROUND: Abdominal myomectomy is a common modality of treatment for large and symptomatic uterine fibroid in women who wish to retain their fertility. Though frequently performed the procedure may still be associated with complications. MATERIALS AND METHODS: A retrospective review of all patients who had abdominal myomectomy from January 1999 to December 2008 at the University of Maiduguri Teaching Hospital. Information on the Sociodemographic characteristics, indication for the myomectomy, uterine size, pre and post operative packed cell volume (PCV), intraoperative findings, cadre of surgeon, duration of hospital stay and complications were obtained. RESULTS: The rate of abdominal myomectomy was 3.34%. Majority of the patients (79.8%) aged 30-49 years, and most (58.9%) were nulliparas. Abdominal mass (63.7%), menorrhagia (57.7%), and subfertility 55.2% were the leading indications for abdominal myomectomy. Complications were seen in 10.9% of the cases, 55.5 % of which were wound infections. Clinical and intra operative factors associated with complications included menorrhagia (P=0.003), estimated blood loss (EBL) >=500mls (P=0.005) and post operative PCV of <30% (P=0.081). CONCLUSION: Complication rate after myomectomy was low with menorrhagia and EBL >= 500 mls being significantly associated with development of complication. PMID- 22083373 TI - Detection and determination of manganese concentration in water using a fiber Bragg grating coupled with nanotechnology. AB - Through this paper we experimentally demonstrate the fabrication of a fiber Bragg grating (FBG) chemical sensor to detect and determine the manganese concentration in water and compare our results with sophisticated spectroscopic methods, such as atomic absorption spectrometry and the inductively coupled plasma method. Here we propose a simple method to develop a thin layer of gold nanoparticles above the etched grating region to enhance the sensitivity of the reflected spectrum of the FBG. By doing so, we achieve a sensitivity of 1.26 nm/parts per million in determining the trace level of Mn in water. Proper reagents are used to detect manganese in water. PMID- 22083374 TI - High precision dynamic multi-interface profilometry with optical coherence tomography. AB - Optical coherence tomography (OCT) has mostly been used for high-speed volume imaging but its profilometry potentials have not been fully exploited. This paper demonstrates high precision (as good as ~50 nm) multi-interface profilometry using a Fourier domain OCT system without special antivibration devices. The precision is up to 2 orders of magnitude better than the depth resolution of the OCT. Detailed analysis of the precision achieved for different surfaces is presented. The multi-interface profiles are obtained as a by-product of the tomography data. OCT has the advantage in speed and sensitivity at detecting rough and internal interfaces versus conventional optical profilometry. An application of the technique to the dynamic monitoring of varnish drying on paintlike substrates is demonstrated, which provides a better understanding of the formation of surface roughness. The technique has potential benefits in the fields of art conservation, coatings technology, and soft matter physics. PMID- 22083371 TI - The use of external fixation combined with vacuum sealing drainage to treat open comminuted fractures of tibia in the Wenchuan earthquake. AB - PURPOSE: The purpose of this study was to review the results of external fixation combined with vacuum sealing drainage (VSD) to treat patients who sustained tibial and fibular fractures in the Wenchuan earthquake. METHODS: We retrospectively analysed 179 cases (of which 85 were classified as Gustilo grade III) of open comminuted fracture of the tibia and fibula caused by the Wenchuan earthquake. The patients were followed up for an average of 15 months; detailed records were kept on their function and recovery. RESULTS: After caring for the life-threatening injuries; fractures were treated by external fixation, with VSD used on the surface or in the cavity of the wound after debridement. Antibiotics were administered on the basis of drug sensitivity test results. After the infection had been controlled and healthy granulation tissue had developed, the patients underwent secondary suture, free skin grafting, or skin flap transfer. CONCLUSION: Good results can be achieved when external fixation combined with vacuum sealing drainage were used to treat open comminuted fractures of tibia and fibula in the Wenchuan earthquake. PMID- 22083375 TI - Optical programmable Boolean logic unit. AB - Logic units are the building blocks of many important computational operations likes arithmetic, multiplexer-demultiplexer, radix conversion, parity checker cum generator, etc. Multifunctional logic operation is very much essential in this respect. Here a programmable Boolean logic unit is proposed that can perform 16 Boolean logical operations from a single optical input according to the programming input without changing the circuit design. This circuit has two outputs. One output is complementary to the other. Hence no loss of data can occur. The circuit is basically designed by a 2*2 polarization independent optical cross bar switch. Performance of the proposed circuit has been achieved by doing numerical simulations. The binary logical states (0,1) are represented by the absence of light (null) and presence of light, respectively. PMID- 22083376 TI - Measurement of the surface profile of an axicon lens with a polarization phase shifting shearing interferometer. AB - We present a Twyman-Green interferometer (TGI)-based polarization phase-shifting shearing interferometric technique for testing the conical surface of an axicon (AX) lens. In this technique, the annular beam generated due to the passing of an expanded collimated laser beam traveling along the axis of revolution of the transparent glass AX element is split up into its reflected and transmitted components, having the plane of polarization in the orthogonal planes, by the polarization beam splitter (PBS) cube of the TGI-based optical setup. The split up components are made to travel unequal paths along the two arms of the TGI and are recombined by the PBS. Because of the difference in path lengths traveled by the annular conical beams, a linear shear is introduced along the radial direction between the interfering components. Thus, the resulting interference pattern gives a map of the optical path difference (OPD) between two successive close points along a radial direction on the conical surface of the AX lens. The OPD map along radial directions, and hence the slopes/profiles of the conical surface, are obtained by applying polarization phase-shifting interferometry. Results obtained for an AX lens are presented. PMID- 22083377 TI - Information-theoretic analysis of a stimulated-Brillouin-scattering-based slow light system. AB - We use an information-theoretic method developed by Neifeld and Lee [J. Opt. Soc. Am. A 25, C31 (2008)] to analyze the performance of a slow-light system. Slow light is realized in this system via stimulated Brillouin scattering in a 2 km long, room-temperature, highly nonlinear fiber pumped by a laser whose spectrum is tailored and broadened to 5 GHz. We compute the information throughput (IT), which quantifies the fraction of information transferred from the source to the receiver and the information delay (ID), which quantifies the delay of a data stream at which the information transfer is largest, for a range of experimental parameters. We also measure the eye-opening (EO) and signal-to-noise ratio (SNR) of the transmitted data stream and find that they scale in a similar fashion to the information-theoretic method. Our experimental findings are compared to a model of the slow-light system that accounts for all pertinent noise sources in the system as well as data-pulse distortion due to the filtering effect of the SBS process. The agreement between our observations and the predictions of our model is very good. Furthermore, we compare measurements of the IT for an optimal flattop gain profile and for a Gaussian-shaped gain profile. For a given pump beam power, we find that the optimal profile gives a 36% larger ID and somewhat higher IT compared to the Gaussian profile. Specifically, the optimal (Gaussian) profile produces a fractional slow-light ID of 0.94 (0.69) and an IT of 0.86 (0.86) at a pump-beam power of 450 mW and a data rate of 2.5 Gbps. Thus, the optimal profile better utilizes the available pump-beam power, which is often a valuable resource in a system design. PMID- 22083378 TI - Dirac bra-ket in radiometry of quasi-homogeneous sources. AB - The concept of "throughput" is used in traditional radiometry of Lambertian sources for computing and estimating the radiant flux passed through a pair of stops, in particular through the window and the pupil of an optical system. It is shown that in a more general case of quasi-homogeneous sources for energetic calculations of the perfect optical system, one must use instead of the throughput a functional that is similar to the famous "Dirac bra-ket." This functional takes into account the radiation pattern of the source. As the Dirac bra-ket satisfies the axioms of the inner product, powerful mathematical tools of functional analysis for the energy calculation of the optical systems are used. The main equations and principles of radiometry (the principle of reversibility and Maxwell's principle) are reformulated from the concept "throughput" into the concept "Dirac bra-ket." For generalization of Maxwell's principle to the class of quasi-homogeneous sources the concept of "effective stops" is introduced. PMID- 22083379 TI - 3D video visualization employing wavelet multilevel decomposition. AB - This study analyzed the implementation and performance of a framework that can be efficiently applied to three-dimensional (3D) video sequence visualization. The proposed algorithm is based on wavelets and wavelet atomic functions used in the computation of disparity maps. The proposed algorithm employs wavelet multilevel decomposition and 3D visualization via color anaglyphs synthesis. Simulations were run on synthetic images, synthetic video sequences, and real-life video sequences. Results shows that this novel approach performs better in depth and spatial perception tasks compared to existing methods, both in terms of objective criteria such as quantity of bad disparities and similarity structural index measure and the more subjective measure of human vision. PMID- 22083381 TI - Passive frequency stabilization in Nd:YAG pulse laser using reflective volume Bragg grating. AB - We demonstrate a stable Q-switched single-longitudinal-mode (SLM) Nd:YAG laser using a volume Bragg grating as the output coupler. The reflective volume Bragg grating, serving as a longitudinal selector and passive frequency stabilizer, effectively eliminates the mode hopping effect of the laser. The maximum output energy of the SLM obtained from the current experimental setup is 18.5 mJ. The maximum separation of frequencies is significantly less than the longitudinal mode separation, indicating that a stable SLM laser is achieved. PMID- 22083382 TI - Evolution process from ghost diffraction to ghost imaging in a lensless imaging system. AB - Ghost diffraction and ghost imaging are investigated in a lensless imaging system. The evolution process from ghost diffraction to ghost imaging is discussed when the object is moved far away from the source in the test arm. The relation of ghost diffraction and imaging is also studied, and it is found that the visibility of ghost imaging is always better than that of ghost diffraction. PMID- 22083383 TI - Analytical approach to thermal lensing in end-pumped Yb:YAG thin-disk laser. AB - Thermal lensing in the thin-disk laser influences the output beam quality and optical efficiency significantly. In this paper, an analytical approach is taken to study the production mechanisms, features, and influences of thermal lensing in the end-pumped thin-disk laser. We calculate the distributions of temperature, stress, strain, and expansion in the disk and the curvature of the crystal using an analytic method. The expressions of the thermal lens focal length depending on the radius are presented. The optical path difference, a major cause of thermal lensing, is induced by the thermo-optical effect, the photoelastic effect, and inhomogeneous distribution of thermal expansion and the excited population. Thermal lensing is found to be aspheric with undesired aberrations and birefringence effects. Furthermore, a convex mirror due to the axial temperature gradient occurs in a free disk, and the convex mirror is found to be spherical in the center region of the disk. Based on the results of our analysis, the aspect ratio and size of the laser mode of the gain region may be adjusted to limit the damaging effects of thermal lensing. PMID- 22083384 TI - Nonmechanical transverse scanning laser Doppler velocimeter using wavelength change. AB - A transverse scanning laser Doppler velocimeter (LDV) that does not require any moving mechanism in its sensor probe is proposed, and the scanning function is demonstrated theoretically and experimentally. In the proposed scanning LDV, the measurement position is transversely scanned on the basis of a wavelength change induced by a tunable laser and a combination of a grating and a Dove prism. To demonstrate the scanning function in the transverse direction, an experiment was carried out using a setup of the sensor probe consisting of bulk optical components. The experimental results indicate that a transverse scanning function was successfully obtained. The scanning range in the vertical direction is estimated to be 11.3 mm over wavelengths of 1520 to 1570 nm. PMID- 22083385 TI - Effects of manufacturing errors on diffraction efficiency for multilayer diffractive optical elements. AB - The effect of manufacturing errors on diffraction efficiency for multilayer diffractive optical elements (MLDOEs) used in imaging optical systems is discussed in this paper. The relationship of diffraction efficiency and depth scaling errors are analyzed for two different cases: the two relative depth scaling errors change in the same sign and in the opposite sign. For the first condition, the corresponding diffraction efficiency decreases more slowly. The effect of periodic width errors on diffraction efficiency is also evaluated. When the two major manufacturing errors coexist, the magnitude of the decrease of diffraction efficiency is analyzed for MLDOEs. The result can be used for analyzing the effects of the manufacturing errors on diffraction efficiency for MLDOEs. PMID- 22083386 TI - Influences of pyramid prism deflection on inversion of wind velocity and temperature in a novel static polarization wind imaging interferometer. AB - The principle of the novel static polarization wind imaging interferometer (NSPWII) [Acta Opt. Sin. 28, 700 (2008)] based on a pyramid prism is described. Since the measured wind velocity and temperature depend on the transmittance of the pyramid prism, the deflection of the prism introduced by vibration would produce some measuring errors. In this paper, with an assumed deflection case, we analyze its influence on the derived wind velocity and temperature theoretically. The relative error of the inversion temperature and variety of the inversion velocity as they changed with the deflection angle are discussed. PMID- 22083387 TI - Comparison of structure and performance between extended blue and standard transmission-mode GaAs photocathode modules. AB - Extended blue and standard transmission-mode GaAs photocathode modules were prepared, respectively, by metal organic chemical vapor deposition. The experimental reflectivity, transmissivity, and spectral response curves were measured and compared separately. The integral sensitivities are 1980 MUA/lm and 2022 MUA/lm for both the modules. By use of the revised quantum yield formula, the experimental spectral response curves are fitted to obtain the structure parameters. The fitted results show that the Ga(1-x)Al(x)As window layer with varied aluminum components is beneficial to improve extended blue GaAs photocathode module. In addition, the layer-thickness and aluminum component in the window layer determine the extended blue performance, while the thickness of the GaAs active layer settles the long-waveband performance for the transmission mode GaAs photocathode module. PMID- 22083388 TI - Prediction formulas for nasal continuous positive airway pressure in patients with obstructive sleep apnea syndrome. PMID- 22083389 TI - Synthesis of functionalized tetrahydro-1,3-diazepin-2-ones and 1-carbamoyl-1H pyrroles via ring expansion and ring expansion/ring contraction of tetrahydropyrimidines. AB - A general approach to 6-phenylthio-substituted 2,3,4,5-tetrahydro-1H-1,3-diazepin 2-ones based on the ring expansion reaction of 1,2,3,4-tetrahydropyrimidin-2-ones under the action of nucleophiles has been developed. The first step of the synthesis was preparation of N-[(2-benzoyloxy-1-tosyl)ethyl]urea by three component condensation of 2-benzoyloxyethanal, urea and p-toluenesulfinic acid. Nucleophilic substitution of the tosyl group in the obtained sulfone with sodium enolates of alpha-phenylthioketones followed by cyclization-dehydration, and debenzoylation gave 4-hydroxymethyl-5-phenylthio-1,2,3,4-tetrahydropyrimidin-2 ones which were transformed into the 4-mesyloxymethyl-derivatives. Treatment of the latter with nucleophilic reagents, such as NaCN, sodium diethyl malonate, PhSNa, MeONa, NaBH(4), sodium succinimide, or potassium phthalimide, afforded the target multi-functionalized diazepinones. The obtained 6-phenylthio-diazepinones and their 6-tosyl-substituted analogues were converted into 3-substituted 1 carbamoyl-1H-pyrroles under acidic conditions as a result of ring contraction. Effective one-pot synthesis of the latter from 4-mesyloxymethyl-pyrimidines was realized using a ring expansion/ring contraction sequence. PMID- 22083390 TI - The relationships between employment, clinical status, and psychiatric hospitalisation in patients with schizophrenia receiving either IPS or a conventional vocational rehabilitation programme. AB - PURPOSE: Positive relationships between employment and clinical status have been found in several studies. However, an unequivocal interpretation of these relationships is difficult on the basis of common statistical methods. METHODS: In this analysis, a structural equation model approach for longitudinal data was applied to identify the direction of statistical relationships between hours worked, clinical status and days in psychiatric hospital in 312 persons with schizophrenia who participated in a multi-centre randomised controlled trial comparing the effectiveness of Individual Placement and Support (IPS) with conventional vocational services in six study settings across Europe. Data were analysed by an autoregressive cross-lagged effects model, an autoregressive cross lagged model with random intercepts and an autoregressive latent trajectory model. RESULTS: Comparison of model fit parameters suggested the autoregressive cross-lagged effects model to be the best approach for the given data structure. All models indicated that patients who received an IPS intervention spent more hours in competitive employment and, due to indirect positive effects of employment on clinical status, spent fewer days in psychiatric hospitals than patients who received conventional vocational training. CONCLUSIONS: Results support the hypothesis that the IPS intervention has positive effects not only on vocational but also on clinical outcomes in patients with schizophrenia. PMID- 22083393 TI - The vasodilator stress ECG: should depression cause anxiety? PMID- 22083394 TI - In vitro azadirachtin production by hairy root cultivation of Azadirachta indica in nutrient mist bioreactor. AB - Azadirachtin, a well-known biopesticide is a secondary metabolite conventionally extracted from the seeds of Azadirachta indica. The present study involved in vitro azadirachtin production by developing hairy roots of A. indica via Agrobacterium rhizogenes-mediated transformation of A. indica explants. Liquid culture of hairy roots was established in shake flask to study the kinetics of growth and azadirachtin production. A biomass production of 13.3 g/L dry weight (specific growth rate of 0.7 day(-1)) was obtained after 25 days of cultivation period with an azadirachtin yield of 3.3 mg/g root biomass. To overcome the mass transfer limitation in conventionally used liquid-phase reactors, batch cultivation of hairy roots was carried out in gas-phase reactors (nutrient spray and nutrient mist bioreactor) to investigate the possible scale-up of A. indica hairy root culture. The nano-size nutrient mist particles generated from the nozzle of the nutrient mist bioreactor could penetrate till the inner core of the inoculated root matrix, facilitating uniform growth during high-density cultivation of hairy roots. A biomass production of 9.8 g/L dry weight with azadirachtin accumulation of 2.8 mg/g biomass (27.4 mg/L) could be achieved in 25 days of batch cultivation period, which was equivalent to a volumetric productivity of 1.09 mg/L per day of azadirachtin. PMID- 22083391 TI - Executive summary of the report by the WPA section on pharmacopsychiatry on general and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders. AB - Current gold standard in the treatment of depression includes pharmacotherapeutic and psychotherapeutic strategies together with social support. Due to the actually discussed controversies concerning the differential efficacy of antidepressants, a contribution to a comprehensive clarification seems to be necessary to avert further deterioration and uncertainty from patients, relatives, and their treating psychiatrists and general practitioners. Both efficacy and clinical effectiveness of antidepressants in the treatment of depressive disorders can be confirmed. Clinically meaningful antidepressant treatment effects were confirmed in different types of studies. Methodological issues of randomized controlled studies, meta-analyses, and effectiveness studies will be discussed. Furthermore, actual data about the differential efficacy and effectiveness of antidepressants with distinct pharmacodynamic properties and about outcome differences in studies using antidepressants and/or psychotherapy are discussed. This is followed by a clinically oriented depiction-the differential clinical effectiveness of different pharmacodynamic modes of action of antidepressants in different subtypes of depressive disorders. It can be summarized that the spectrum of different antidepressant treatments has broadened during the last decades. The efficacy and clinical effectiveness of antidepressants is statistically significant and clinically relevant and proven repeatedly. For further optimizing antidepressant treatment plans, clearly structured treatment algorithms and the implementation of psychotherapy seem to be useful. A modern individualized antidepressant treatment in most cases is a well-tolerated and efficacious tool to minimize the negative impact of the otherwise devastating and life-threatening outcome of depressive disorders. PMID- 22083395 TI - Genome shuffling enhanced epsilon-poly-L-lysine production by improving glucose tolerance of Streptomyces graminearus. AB - The productivity of epsilon-poly-L: -lysine (epsilon-PL) in currently reported wild-type strains is low. Here we improved glucose tolerance of a Streptomyces graminearus strain LS-B1 by genome shuffling while simultaneously enhancing the epsilon-PL productivity. The starting population was generated by ultraviolet irradiation and nitrosoguanidine mutagenesis and then subjected for recursive protoplast fusion. The positive colonies from library, created by fusing the inactivated protoplasts were screened on agar plates containing different concentrations of glucose. Characterization of all recombinants and wild-type strain in shake-flask fermentation indicated the compatibility of two phenotypes of glucose tolerance and epsilon-PL yield enhancement. The best performing recombinant, F3-4, was isolated after three rounds of genome shuffling, whose epsilon-PL production was about 88% higher than that of the parent strain. In batch fermentation test, the epsilon-PL concentration was obtained as 2.4 g/L by F3-4 compared with 1.6 g/L of wild type. Fed-batch fermentation by F3-4 was carried out and the epsilon-PL production accumulated to 13.5 g/L when initial glucose concentration was improved from 50 to 85 g/L. Enzyme activities of hexokinase, pyruvate kinase, and citrate synthase revealed that the glycolytic pathway and tricarboxylic acid circle way in F3-4 were more active than those in wild type, which was a possible reason for enhanced epsilon-PL production. PMID- 22083397 TI - Geochemical evidence for the origin of vanadium in an urban environment. AB - The city of Salamanca in central Mexico is surrounded by heavy industry, i.e., a refinery, a thermoelectric plant and chemical industries. Variable concentrations of vanadium (V) have been reported in the groundwater, and their presence has been related to particulates so this hypothesis was tested by sampling soil in the urban area and the surrounding uncontaminated country site. The 0-10-cm soil layer in the industrial and rural area was analyzed for V and other metal trace elements found in hydrocarbons, i.e., chromium (Cr), lead (Pb), zinc (Zn), and nickel (Ni). The concentrations of V were higher in the urban rather than in the rural soil, reaching values of >600 mg kg(-1) in the urban soils. In the rural area, V in the soil was related to regional geology, i.e., volcanic rocks such as basalts and rhyolites but not in the urban area where it was related to particulate distribution mostly emitted from the industries burning fuel oil number 6. PMID- 22083398 TI - Development of fuzzy air quality index using soft computing approach. AB - Proper assessment of air quality status in an atmosphere based on limited observations is an essential task for meeting the goals of environmental management. A number of classification methods are available for estimating the changing status of air quality. However, a discrepancy frequently arises from the quality criteria of air employed and vagueness or fuzziness embedded in the decision making output values. Owing to inherent imprecision, difficulties always exist in some conventional methodologies like air quality index when describing integrated air quality conditions with respect to various pollutants parameters and time of exposure. In recent years, the fuzzy logic-based methods have demonstrated to be appropriated to address uncertainty and subjectivity in environmental issues. In the present study, a methodology based on fuzzy inference systems (FIS) to assess air quality is proposed. This paper presents a comparative study to assess status of air quality using fuzzy logic technique and that of conventional technique. The findings clearly indicate that the FIS may successfully harmonize inherent discrepancies and interpret complex conditions. PMID- 22083399 TI - Chemometric study on the trace metal accumulation in the sediments of the Cochin Estuary--Southwest coast of India. AB - The distribution and accumulation of trace metals in the sediments of the Cochin estuary during the pre-monsoon, monsoon and post-monsoon periods were investigated. Sediment samples from 14 locations were collected and analysed for the metal contents (Mg, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb), organic carbon, total nitrogen, total sulphur and grain size. The data were processed using statistical tools like correlation, factor and cluster analysis. The study revealed an enrichment of Cd and Zn in the study area particularly at station 2, which is confirmed by enrichment factor, contamination factor and geoaccumulation index. The factor analysis revealed that the source of Cd and Zn may be same. The study indicated that the spatial variation for the metals like Mg, Cr, Fe, Co, Ni, Cu, Zn, Cd and Pb were predominant unlike Mn which shows a temporal variation. The strong association of trace metals with Fe and Mn hydroxides and oxides are prominent along the Cochin estuary. The anthropogenic inputs of industrial effluents mainly control the trace metals enrichment in the Cochin estuary. PMID- 22083400 TI - Soil pollution under the effect of treated municipal wastewater. AB - Soil heavy metal pollution due to wastewater reuse was assessed by means of the concentration factor (CF) and/or pollution load index (PLI).In this respect, a greenhouse pot experiment was conducted, using a completely randomized block design, including five treatments of treated municipal wastewater (0%, 25%, 50%, 75%, and 100%), in four replications. Brassica oleracea var. Capitata was used as a test crop. The optimum CFs were expressed as a function of maximum dry matter of cabbage plant parts yield, and the values obtained per plant part were as follows: stems-Zn-CF 2.96, Co-CF 0.85, Ni-CF 0.92; whole plant-Cu-CF 3.90, Ni-CF 0.87, and Pb-CF 11.52; and leaves-Pb-CF 11.78. The PLI was calculated as the geometric mean of the CF of each metal, and was related to the maximum dry mater yield of cabbage stems and heads. The optimum values found were: stems PLI 1.99 2.55 and heads 2.25. PMID- 22083402 TI - Square wave adsorptive stripping voltammetric determination of diazinon in its insecticidal formulations. AB - The pesticide diazinon was determined in its insecticidal formulations by square wave adsorptive stripping voltammetry. The method of its determination is based on the irreversible reduction reaction at the hanging mercury drop electrode. The optimal signal was detected at -1.05 V vs. Ag/AgCl in Britton-Robinson buffer at pH 4.4. Various parameters such as pH, buffer concentration, frequency, amplitude, step potential, accumulation time, and potential were investigated to enhance the sensitivity of the determination. The highest response was recorded at an accumulation potential -0.4 V, accumulation time 60 s, amplitude 75 mV, frequency 100 Hz, and step potential 5 mV. The pesticide electrochemical behavior was considered under experimental conditions. The electroanalytical procedure enabled diazinon determination in the concentration range 4.0 * 10(-8)-3.9 * 10( 7) mol L(-1) in supporting electrolyte. The detection and quantification limit were found to be 1.1 * 10(-8) and 3.7 * 10(-8) mol L(-1), respectively. The method was applied successfully in the determination of the active ingredients in the insecticidal formulations Diazinon 10GR and Beaphar 275. PMID- 22083401 TI - Study of electromagnetic radiation pollution in an Indian city. AB - Electromagnetic radiation emitted by cell phone towers is a form of environmental pollution and is a new health hazard, especially to children and patients. The present studies were taken to estimate the microwave/RF pollution by measuring radiation power densities near schools and hospitals of Chandigarh city in India. The cell phone radiations were measured using a handheld portable power density meter TES 593 and specific absorption rates were estimated from the measured values. These values of electromagnetic radiation in the environment were compared with the levels at which biological system of humans and animals starts getting affected. The values were also compared with the international exposure limits set by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). The highest measured power density was 11.48 mW/m(2) which is 1,148% of the biological limit. The results indicated that the exposure levels in the city were below the ICNIRP limit, but much above the biological limit. PMID- 22083403 TI - Effects of selected soil properties on phytoremediation applicability for heavy metal-contaminated soils in the Apulia region, Southern Italy. AB - Phytoremediation is a well-known promising alternative to conventional approaches used for the remediation of diffused and moderated contaminated soils. The evaluation of the accumulation, availability, and interactions of heavy metals in soil is a priority objective for the possible use of phytoremediation techniques such as phytoextraction and phytostabilization. The soils used in this work were collected from a number of sites inside a protected area in the Apulia region (Southern Italy), which were contaminated by various heavy metals originated from the disposal of wastes of different sources of origin. Soils examined contained Cd, Cr, Cu, Ni, Pb, and Zn in amounts exceeding the critical limits imposed by EU and Italian laws. However, the alkaline conditions, high organic matter content, and silty to silty loamy texture of soils examined would suggest a reduced availability of heavy metals to plants. Due to the high total content but the low available fraction of heavy metals analyzed, especially Cr, phytoextraction appears not to be a promising remediation approach in the sites examined, whereas phytostabilization appears to be the best technique for metal decontamination in the studied areas. PMID- 22083404 TI - Effect of various refrigeration temperatures on quality of shell eggs. AB - BACKGROUND: The objective of this study was to evaluate the effects of low storage temperatures on shell egg quality. RESULTS: Approximately 2100 shell eggs were collected and stored at - 1.1, 0.6, 2.2, 3.9, 5.6 and 7.2 degrees C for up to 4 weeks. Eighteen eggs at each storage temperature were evaluated after 0, 2, 7, 14, 21 and 28 days of storage. Haugh units (HU), yolk index (YI), albumen pH (pHA), yolk pH (pHY) and angel food cake density (CD) were measured. Shell egg quality tended to be preserved better at below 2.2 degrees C, as high HU and YI values relative to eggs stored at 7.2 degrees C were determined on day 28. However, storage at - 1.1 degrees C tended to cause the opposite effect, especially highly declined HU values over time. Significantly different HU values of shell eggs were measured after 14 days of storage, with eggs stored at 0.6 and 2.2 degrees C having the highest HU values, 80.42 and 77.97 respectively. CONCLUSION: A lower temperature limit for shell egg storage could be established between 0.6 and 2.2 degrees C, as both temperatures showed the highest HU values, 77.88 and 77.60 respectively, after 28 days of storage. PMID- 22083405 TI - Determination of normal dimension of the spleen by ultrasound in an endemic tropical environment. AB - BACKGROUND: To determine the normal dimensions of spleen by ultrasonography in our environment exposed to endemic tropical infection and infestation. MATERIALS AND METHODS: A prospective study of normal spleen ultrasound-based measurements in 200 Nigerian adults at the University of Benin Teaching Hospital Benin, Nigeria. RESULTS: There were 91 males and 109 females; their age ranged between 20 and 60 years. For the males the mean age was 32.4 years (+/- 9.2 SD), mean height was 175.0 cm (+/-7.3 SD), mean weight was 72.5 kg (+/-10.1 SD), and mean body mass index was 23.6 (+/-2.8 SD) and the females the mean age was 29.7 years (+/-9.0 SD) mean height was 164.6 cm (+/-5.8 SD), mean weight 64.1 kg (+/-12.9 SD), and mean BMI was 24.9 (+/-1.4 SD). For the males the mean splenic length, width, depth, and volume were 11.1 cm (+/-0.9 SD), 4.4 cm (+/-0.5 SD), 7.8 cm (+/ 0.6 SD), and 202.7 cm(3) (+/-49.4 SD), respectively. For the females the corresponding values of splenic length, width, depth, and volume were 10.1 cm (+/ 0.7 SD), 4.0 cm (+/-0.4 SD), 7.1 cm (+/-0.5 SD), and 153.7 cm(3) (+/-33.2 SD), respectively. CONCLUSION: Comparison between mean splenic dimension parameters for males and females (from unpaired t-test determination) showed a statistically significant difference (P<0.001 for splenic length, width, depth, and volume). There was also statistically significant increasing value correlation between subjects' weight and height (in favor of height) when compared to spleen length, width, depth, and volume. The other parameters show no significant correlation in both female and male. In particular there was also no statistically significant correlation of splenic measurements with age in either sex. This is similar to what was noted in other centers. PMID- 22083406 TI - A thermal manikin with human thermoregulatory control: implementation and validation. AB - Tens of different sorts of thermal manikins are employed worldwide, mainly in the evaluation of clothing thermal insulation and thermal environments. They are regulated thermally using simplified control modes. This paper reports on the implementation and validation of a new thermoregulatory control mode for thermal manikins. The new control mode is based on a multi-segmental Pierce (MSP) model. In this study, the MSP control mode was implemented, using the LabVIEW platform, onto the control system of the thermal manikin 'Therminator'. The MSP mode was then used to estimate the segmental equivalent temperature (t(eq)) along with constant surface temperature (CST) mode under two asymmetric thermal conditions. Furthermore, subjective tests under the same two conditions were carried out using 17 human subjects. The estimated segmental t(eq) from the experiments with the two modes and from the subjective assessment were compared in order to validate the use of the MSP mode for the estimation of t(eq). The results showed that the t(eq) values estimated by the MSP mode were closer to the subjective mean votes under the two test conditions for most body segments and compared favourably with values estimated by the CST mode. PMID- 22083407 TI - Stem cell transplantation in an in vitro simulated ischemia/reperfusion model. AB - Stem cell transplantation protocols are finding their way into clinical practice. Getting better results, making the protocols more robust, and finding new sources for implantable cells are the focus of recent research. Investigating the effectiveness of cell therapies is not an easy task and new tools are needed to investigate the mechanisms involved in the treatment process. We designed an experimental protocol of ischemia/reperfusion in order to allow the observation of cellular connections and even subcellular mechanisms during ischemia/reperfusion injury and after stem cell transplantation and to evaluate the efficacy of cell therapy. H9c2 cardiomyoblast cells were placed onto cell culture plates. Ischemia was simulated with 150 minutes in a glucose free medium with oxygen level below 0.5%. Then, normal media and oxygen levels were reintroduced to simulate reperfusion. After oxygen glucose deprivation, the damaged cells were treated with transplantation of labeled human bone marrow derived mesenchymal stem cells by adding them to the culture. Mesenchymal stem cells are preferred in clinical trials because they are easily accessible with minimal invasive surgery, easily expandable and autologous. After 24 hours of co cultivation, cells were stained with calcein and ethidium-homodimer to differentiate between live and dead cells. This setup allowed us to investigate the intercellular connections using confocal fluorescent microscopy and to quantify the survival rate of postischemic cells by flow cytometry. Confocal microscopy showed the interactions of the two cell populations such as cell fusion and formation of intercellular nanotubes. Flow cytometry analysis revealed 3 clusters of damaged cells which can be plotted on a graph and analyzed statistically. These populations can be investigated separately and conclusions can be drawn on these data on the effectiveness of the simulated therapeutical approach. PMID- 22083408 TI - Uterine fibroids: Which treatment? PMID- 22083409 TI - Rhytidoplasty without periauricular scar. AB - As plastic surgeons, it has always been our goal to reduce the scarring associated with facial plastic surgeries. These scars generally occur on the scalp and in both the pre- and retroauricular areas. In 194 of our patients who underwent rhytidoplasties, we successfully eliminated these retroauricular and preauricular scars. To achieve these results, we did not make periauricular incisions; instead, we made a superior incision, a subcutaneous dissection, and used various surgical maneuvers such as subdermal plication and structural grafting. By utilizing this facelift technique, we were able to eliminate the appearance of periauricular scars associated with facial plastic surgery, reduce complications, achieve natural-looking results, and increase patient satisfaction. PMID- 22083410 TI - Primary nasal tip surgery: a conservative approach. AB - BACKGROUND: Rhinoplasty and rhinoseptoplasty are very important and complex surgical procedures because the nose plays a pivotal aesthetic role in the face and an important functional role in breathing. Mild bulbous, plunging, undefined tips are very common, and tip refining and repositioning often are required surgical procedures. METHODS: For 97 selected patients, the authors performed their personal technique consisting of a transcartilaginous approach, incomplete vertical interruption, and retrograde undermining of the lower lateral cartilages to improve tip projection and definition. The five aspects analyzed were nasal tip symmetry, nostril symmetry, tip projection, tip definition, and appearance of the nasal tip only. Each parameter was assessed using pre- and postoperative quantification according to a visual analog scale. Postoperative evaluation was performed during a mean follow-up period of 1 year. RESULTS: The results at 1 year showed high rates of improvement in tip definition (mean, 7.9+/-2.4) and nasal tip only evaluation (mean, 6.5+/-3.1). The patients reported an improvement in nasal tip symmetry (mean, 4.2+/-3.2), nostril symmetry (mean, 4.5+/-4.1), and tip projection (mean, 5.8+/-2.9). CONCLUSIONS: This simple, safe, and effective technique is proposed for mild bulbous, plunging, undefined, and hypoprojected tips. PMID- 22083411 TI - Subfascial breast augmentation: is there any advantage over the submammary plane? AB - Subfascial (SF) breast augmentation has been proposed as an alternative to placement of a breast prosthesis in a subpectoral (SP) or direct submammary (SM) plane, producing advantages over both techniques. This study compares complication rates in 200 SF-placed implants with 83 SM implants, undertaken over a 51-month period by a single surgeon. No statistical difference was found in the complication rate or patient satisfaction of one technique over the other. No clinical advantage can be demonstrated by placing breast prostheses behind the pectoral fascia compared to directly behind the breast. PMID- 22083412 TI - A study of postural changes after breast augmentation. AB - BACKGROUND: A number of factors, including body mass and one's mood, may influence posture. Breast augmentation results not only in a significant improvement in body image-related feelings and self-esteem but also in a sudden change in body mass. The aim of this study was to assess postural changes following breast augmentation by studying body position, orientation through space, and center of pressure. METHODS: Patients with breast hypoplasia who underwent breast augmentation were enrolled. Posture evaluation was performed before and 1, 4, and 12 months after surgery by quantifying the center of mass using the FastrakTM system and the center of pressure using stabilometry. The Wilcoxon signed-rank sum test was used to compare value modifications. RESULTS: Forty-eight patients were enrolled in the study. A retropositioning of the upper part of the body, confirmed by baropodometric analysis, was evident in the early postoperative period. We subsequently observed a reprogramming of the biomechanical system, which reached a state of equilibrium 1 year after surgery, with a slight retropositioning of the head and a compensatory anterior positioning of the pelvis. CONCLUSION: We believe that with respect to posture, the role played by psychological aspects is even more important than that played by changes in body mass. Indeed, hypomastia is often associated with kyphosis because patients try to hide what they consider a deficiency. Following breast augmentation, the discovery of new breasts overcomes the dissatisfaction with the patient's own body image, increases self-esteem, and modifies posture regardless of the changes in body mass due to the insertion of the implants. PMID- 22083413 TI - The diagnosis and treatment of thyroid-associated ophthalmopathy. AB - BACKGROUND: Little is written in the plastic surgery literature about thyroid associated ophthalmopathy (TAO), a condition that is separate from Graves-Basedow disease and may not be accompanied by hyperthyroidism. Many patients with this disease frequently seek periocular aesthetic reconstruction prior to medical workup. METHODS: This study presents a comprehensive review of the literature surrounding TAO in order to better understand the prevalence, diagnosis, pathophysiology, and appropriate management of TAO. RESULTS: TAO is frequently under- or misdiagnosed by health-care providers. Patients seeking blepharoplasty or other oculoplastic procedures may have underlying TAO, and the prevalence of TAO in patients who have had a blepharoplasty is approximately 3%. This condition occurs five times more often in women than in men. As a product of the relatively high prevalence of this disease and its underdiagnosis, TAO patients may experience perioperative and late complications due to surgery. CONCLUSION: Blepharoplasties performed on TAO patients must be undertaken with care and insight to avoid cosmetic and functional complications. PMID- 22083414 TI - Sorption of polycyclic aromatic hydrocarbons (PAHs) to low and high density polyethylene (PE). AB - BACKGROUND, AIM, AND SCOPE: According to their high sorption capacity polyethylene (PE) passive samplers are often used for the analysis of polycyclic aromatic hydrocarbons (PAHs) in the aquatic environment. PE is also one of the primary synthetic polymers found in oceans, and sorption of PAHs to marine PE debris may determine PAH exposure and therefore hazards in marine ecosystems. Thus, an understanding of the sorption process is of great importance. In the present study, the sorption of several PAHs with different polarities to low density polyethylene (LDPE) and high density polyethylene (HDPE) was studied in order to improve our understanding of the influence of material properties on the Fickian diffusion of PAHs into PE. MATERIALS AND METHODS: Batch sorption experiments were performed with aqueous solutions containing acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, and LPDE or HDPE pellets. Samples were shaken in the dark at 20 +/- 1 degrees C for 16 time intervals within one week. Concentrations of PAHs were determined in the aqueous samples using solid-phase microextraction coupled with gas chromatography-mass spectrometry. The distribution coefficients (K (PE)) between PE and water were estimated from different models reported in the literature. Kinetic sorption of the PAHs into the plastic pellets was described by a diffusion model based on Fick's second law in spherical coordinates. RESULTS AND DISCUSSION: A comparison between different models describing the equilibrium distribution of PAHs between PE and water revealed that the sorption equilibrium seemed to be driven by parameters other than, or in addition to, organic carbon. For both plastic types, diffusion coefficients decreased while the molecular weight of the PAHs increased which indicates a hindered diffusion through the matrix as a result of a larger molecule size. Higher diffusion coefficients were derived for LPDE than for HDPE indicating a greater sorption velocity for LPDE according to the lower polymer density. CONCLUSIONS: Our results revealed that equilibrium time could be shortened during passive sampling as polymer membranes of lower density are used. In some areas, marine ecosystems may not be in equilibrium with respect to concentrations of organic contaminants and abundance of marine plastic debris. In such cases, different polymer densities should be taken into account in risk assessments. PMID- 22083415 TI - Clinical image: salmonella mycotic aneurysm in a patient receiving etanercept for rheumatoid arthritis. PMID- 22083416 TI - Skeletal rearrangements resulting from reactions of 1,6:2,3- and 1,6:3,4 dianhydro-beta-D-hexopyranoses with diethylaminosulphur trifluoride. AB - A complete series of eight 1,6:2,3- and 1,6:3,4-dianhydro-beta-D-hexopyranoses were subjected to fluorination with DAST. The 1,6:3,4-dianhydropyranoses yielded solely products of skeletal rearrangement resulting from migration of the tetrahydropyran oxygen (educts of D-altro and D-talo configuration) or of the 1,6 anhydro bridge oxygen (D-allo, D-galacto). The major products yielded by the 1,6:2,3-dianhydropyranoses were compounds arising from nucleophilic substitution, with configuration at C4 either retained (D-talo, D-gulo) or inverted (D-manno), or from C6 migration (D-allo). The minor products in the 1,6:2,3-series resulted from migration of the tetrahydropyran oxygen (D-gulo) or the oxirane oxygen (D manno), or from nucleophilic substitution with retention of configuration (D manno). The structure of most of the rearranged products was verified by X-ray crystallography. PMID- 22083417 TI - Adenocarcinoma arising in an intramural diverticulum presenting as a long standing submucosal tumor. AB - We report a rare case of adenocarcinoma arising in a gastric partial diverticulum in the upper portion of the stomach. The lesion had been followed up for approximately 14 years as a gastric submucosal tumor. However, a recent regular check-up revealed mucous material with some neoplastic tissue discharged from the top of the lesion. A surgically resected specimen showed a well-demarcated submucosal lesion identical to a pseudo-diverticulum carrying a distinctive intramucosal minimally invasive adenocarcinoma in part, with surrounding non neoplastic but hyperplastic mucosal components. Intestinal phenotype, along with gastric foveolar, pyloric gland-type phenotypes, and neoplastic cells with neuroendocrine differentiation, were also identified in the adenocarcinoma. Chronic and persistent irritation within the diverticulum was postulated to be implicated in the carcinogenesis of the lesion, which carried no definite Helicobacter pylori microorganisms. We believe it is crucial not to overlook carcinoma in a diverticulum presenting as a long-standing submucosal tumor. PMID- 22083418 TI - A case of lymph node metastasis following a curative endoscopic submucosal dissection of an early gastric cancer. AB - Currently in Japan, differentiated gastric submucosal invasive cancers <500 MUm (SM1) with negative lymphovascular involvement are included in expanded pathological criteria for curative endoscopic treatment. This is based on a retrospective examination of surgical resection cases in which patients suitable for such expanded criteria were determined to have a negligible risk of lymph node metastasis. We performed endoscopic submucosal dissection on a 65-year-old male with early gastric cancer in April 2005, and pathology revealed a well differentiated adenocarcinoma, 21 * 10 mm in size, SM1 invasion depth and negative lymphovascular invasion as well as tumor-free margins, so the case was diagnosed as a curative resection. This case, however, resulted in lymph node metastasis that was diagnosed by endoscopic ultrasonography with fine-needle aspiration biopsy in May 2009. Distal gastrectomy with D2 lymph node dissection was then performed, confirming lymph node metastasis from the original gastric cancer. PMID- 22083419 TI - Quality of life beyond the early postoperative period after laparoscopy-assisted distal gastrectomy: the level of patient expectation as the essence of quality of life. AB - BACKGROUND: The aim of this study was to compare the quality of life after the early postoperative period and before reaching 5 years postoperatively between patients who underwent laparoscopy-assisted distal gastrectomy (Group A) and patients who underwent open distal subtotal gastrectomy (Group B). METHODS: The Korean versions of the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and a gastric cancer-specific module, the EORTC QLQ-STO22, were used to assess the quality of life of 80 patients who underwent laparoscopy-assisted distal gastrectomy or open distal subtotal gastrectomy for gastric cancer. The postoperative period ranged between 6 months and 5 years. RESULTS: The global health status/quality of life scores of Groups A and B were 56.0 +/- 19.0 and 57.4 +/- 18.2, respectively (p = 0.729). Group A experienced worse quality of life in role functioning (p = 0.026), cognitive functioning (p = 0.034), fatigue (p = 0.039), eating restrictions (p = 0.009), and anxiety (p = 0.033). Group A showed a trend to experience worse quality of life in physical functioning, emotional functioning, social functioning, insomnia, and body image, albeit without statistical significance. CONCLUSION: After the early postoperative period and before achieving long-term survival, patients who underwent laparoscopy-assisted distal gastrectomy appeared to experience lower quality of life compared to patients who underwent open distal subtotal gastrectomy. This finding may be associated with the patients' erroneously high expectations of laparoscopy-assisted distal gastrectomy. PMID- 22083420 TI - CD83(+) dendritic cells and Foxp3(+) regulatory T cells in primary lesions and regional lymph nodes are inversely correlated with prognosis of gastric cancer. AB - BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells that are central to the regulation, maturation, and maintenance of the cellular immune response against cancer. In contrast, CD4(+)CD25(+) regulatory T cells (Tregs) play a central role in self-tolerance and suppress antitumor immunity. In this study, we investigated the clinical significance of mature CD83(+) DCs and Foxp3(+) Tregs in the primary tumor and regional lymph nodes from the viewpoint of the two opposing players in the immune responses. METHODS: We investigated, immunohistochemically, the density of CD83(+) DCs and Foxp3(+) Tregs in primary lesions of gastric cancer (n = 123), as well as in regional lymph nodes with (n = 40) or without metastasis (n = 40). RESULTS: Decreased density of CD83(+) DCs and increased density of Foxp3(+) Tregs were observed in the primary tumor and metastatic lymph nodes. Density was significantly correlated with certain clinicopathological features. Poor prognosis was observed in patients with a low density of CD83(+) DCs and a high density of Foxp3(+) Tregs in primary lesions. For patients with metastatic lymph nodes, the density of CD83(+) DCs in negative lymph nodes was found to be an independent prognostic factor by multivariate analysis. CONCLUSION: The density of CD83(+) DCs and Foxp3(+) Tregs was inversely correlated with tumor progression and reflected the prognosis of gastric cancer. PMID- 22083421 TI - Occupational exposure influences on gender differences in respiratory health. AB - BACKGROUND: The aim of this study was to evaluate gender differences in the respiratory health of workers exposed to organic and inorganic dusts. METHODS: Meta-analysis techniques incorporating logistic regression were applied to a combined file of 12 occupational health studies. RESULTS: Meta-analysis of data on 1,367 women and 4,240 men showed that women had higher odds of shortness of breath whether exposed to inorganic dust or having no occupational exposure, with an overall odds ratio (OR) of 2.07 (95% confidence interval [CI] = 1.57-2.73) adjusted for smoking status, age, body mass index (BMI), ethnic status, atopy, and job duration. Inorganic dust exposure was associated with the highest odds of asthma (adjusted OR = 8.38, 95% CI = 1.72-40.89) for women compared to men, but no differences were found for unexposed workers. With organic dust exposure, men had elevated odds for occasional wheeze and worse lung function compared to women. CONCLUSION: Within the limitations of this analysis, gender differences in respiratory health, as suggested by population-based studies, were confirmed in our analysis of occupational health studies, with the general type of exposure, organic or inorganic, generally determining the extent of differences. The higher risks for women compared to men for shortness of breath were robust regardless of work exposure category, with the highest odds ratios found for asthma. PMID- 22083422 TI - [Which hip articulation bearing for which patient? : Tribology of the future]. AB - Replacement of the hip joint has become an exceptionally successful procedure since the inauguration of the low friction principle by Charnley. Aseptic osteolysis and joint dislocation have been addressed by the development of wear optimized materials and the introduction of larger heads. As an increase in head diameter against polyethylene causes wear increase, larger hard-on-hard bearings were introduced, which exhibit reduced wear and reduced dislocation risk with increasing head diameter. These findings were derived from standard simulator testing, not sufficiently considering the risk of fluid film breakdown under adverse conditions, which can cause a dramatic increase in wear and friction proportional to the head diameter. Such adverse conditions can occur clinically in patients due to several factors and have caused the presently observed unexpected problems with these new designs. Standardized preclinical testing has to be viewed as a minimum requirement but certainly not as a guarantee for the clinical success of new materials and designs even if the testing is adapted to the current patient requirements, which is presently not the case. The future of tribology lies in the prevention of adverse conditions in patients, the improvement and optimized use of proven existing materials and not in the use of new materials. PMID- 22083423 TI - Changes in trace metals in hemolymph of baculovirus-infected noctuid larvae. AB - We studied how biologically relevant trace metals (i.e., micronutrients) in the hemolymph of larval Heliothis virescens and Helicoverpa zea (Lepidoptera: Noctuidae) changed in response to per os baculovirus infection, larval development, and injection of heat-killed bacteria. Concentrations of hemolymph Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, and Zn were measured using inductively coupled plasma-mass spectrometry. H. virescens larvae exhibited greater fluctuations in hemolymph trace metal levels in response to baculovirus infection and development than did H. zea larvae. H. zea single nucleopolyhedrosis virus infection significantly altered the levels of Cu, Fe, Mg, Mn, Mo, and Zn in fourth instar H. virescens larvae. Conversely, in fifth instar H. virescens and both H. zea instar infections, no metal levels were significantly different between infected and uninfected larvae. In fourth instar H. virescens hemolymph, Cu, Fe, Mo, and Zn increased during development. Cu, Fe, Mg, Mn, Mo, and Zn levels changed significantly during development in fifth instar H. virescens as well as both H. zea instars. Based on this analysis, metals were identified whose levels changed during development in both species and during the immune response of H. virescens larvae. PMID- 22083424 TI - The interactions of glutathione-capped CdTe quantum dots with trypsin. AB - Due to their unique fluorescent properties, quantum dots present a great potential for biolabelling applications; however, the toxic interactions of quantum dots with biopolymers are little known. The toxic interactions of glutathione-capped CdTe quantum dots with trypsin were studied in this paper using synchronous fluorescence spectroscopy, fluorescence emission spectra, and UV-vis absorption spectra. The interaction between CdTe quantum dots and trypsin resulted in structure changes of trypsin and inhibited trypsin's activity. Fluorescence emission spectra revealed that the quenching mechanism of trypsin by CdTe quantum dots was a static quenching process. The binding constant and the number of binding sites at 288 and 298 K were calculated to be 1.98 * 10(6) L mol(-1) and 1.37, and 6.43 * 10(4) L mol(-1) and 1.09, respectively. Hydrogen bonds and van der Waals' forces played major roles in this process. PMID- 22083425 TI - Anti-genotoxic potential of casein phosphopeptides (CPPs): a class of fermented milk peptides against low background radiation and prevention of cancer in radiation workers. AB - BACKGROUND: Radiation workers are constantly exposed to low background radiation which is their occupational hazard. This continuous and prolonged exposure produces genotoxicity and cancerous condition in many workers. The authors have tested casein phosphopeptides (CPP) as a radioprotectant against low background radiation using animal models. METHODS: Fermented milk was produced by addition of a bacterial culture, Lactobacillus acidophilus to a commercially available milk brand. After the fermentation process is completed in the milk, CPP is isolated from fermented milk by enzymatic hydrolysis-based method. The radioprotective role of CPP was proved using albino mice and Catla catla fish. RESULTS: The micronucleus assay showed higher level of cell deformation and micronucleus formation in the control animal cells than the test animal cells. CPP has found to be having radioprotective activity potential. CONCLUSIONS: This radioprotective potential of CPP can be harnessed to produce formulations which can be used by radiation workers and personnel exposed to low ionization background as an occupational hazard, thus reducing the risk and preventing any type of cancer. PMID- 22083426 TI - Treatment options in end-stage heart failure: where to go from here? AB - Chronic heart failure is a major healthcare problem associated with high morbidity and mortality. Despite significant progress in treatment strategies, the prognosis of heart failure patients remains poor. The golden standard treatment for heart failure is heart transplantation after failure of medical therapy, surgery and/or cardiac resynchronisation therapy. In order to improve patients' outcome and quality of life, new emerging treatment modalities are currently being investigated, including mechanical cardiac support devices, of which the left ventricular assist device is the most promising treatment option. Structured care for heart failure patients according to the most recent international heart failure guidelines may further contribute to optimal decision making. This article will review the conventional and novel treatment modalities of heart failure. PMID- 22083427 TI - Delayed pseudoaneurysm of the internal mammary artery: conservative management. PMID- 22083428 TI - Imaging the prosthetic valve sewing ring thrombosis using real-time three dimensional transoesophageal echocardiography. PMID- 22083429 TI - Pulmonary arterial hypertension: an update. AB - Pulmonary arterial hypertension (PAH), defined as group 1 of the World Heart Organisation (WHO) classification of pulmonary hypertension, is an uncommon disorder of the pulmonary vascular system. It is characterised by an increased pulmonary artery pressure, increased pulmonary vascular resistance and specific histological changes. It is a progressive disease finally resulting in right heart failure and premature death. Typical symptoms are dyspnoea at exercise, chest pain and syncope; furthermore clinical signs of right heart failure develop with disease progression. Echocardiography is the key investigation when pulmonary hypertension is suspected, but a reliable diagnosis of PAH and associated conditions requires an intense work-up including invasive measurement by right heart catheterisation. Treatment includes general measures and drugs targeting the pulmonary artery tone and vascular remodelling. This advanced medical therapy has significantly improved morbidity and mortality in patients with PAH in the last decade. Combinations of these drugs are indicated when treatment goals of disease stabilisation are not met. In patients refractory to medical therapy lung transplantation should be considered an option. PMID- 22083432 TI - Involvement of the capsular genu in reward-related feeding. PMID- 22083431 TI - Personality traits in patients with Parkinson's disease: assessment and clinical implications. AB - This study reviews empirical evidence on the association between personality traits and Parkinson's disease (PD), with a twofold aim. First, to better identify non-motor symptoms, such as affective symptoms and personality changes, that could help to define the pre-motor phase of PD; second, to better understand the neurobiological bases of personality traits, a goal that is not fully accomplished by a purely anatomical approach. A literature review was performed on studies of personality traits in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in July 2011. We found evidence that the existence of a characteristic premorbid personality profile of PD patients is not actually sustained by robust empirical evidence, mainly due to the methodological bias of the retrospective assessment of personality; PD patients present a personality profile of low novelty seeking and high harm avoidance. We concluded that the definition of a pre-motor phase of PD, based on non-motor symptoms, should search for the presence of concomitant affective disorders and for a positive psychiatric history for affective disorders rather than for a typical personality profile or personality changes. The low novelty seeking profile is probably related to the dopaminergic deficit, while the high harm avoidance profile is probably associated with the presence of affective disorders. Clinical implications of these findings, in regard to personality assessment and pharmacological treatments in PD, are also discussed. PMID- 22083433 TI - Emergency surgery in patients who have undergone recent radiotherapy is associated with increased complications and mortality: review of 536 patients. AB - BACKGROUND: There is a paucity of data regarding patients undergoing emergency surgery following radiotherapy. This study examines the morbidity and mortality of patients having emergent surgery <=90 days after irradiation. METHODS: We identified patients >=18 years of age in the American College of Surgeons National Surgical Quality Improvement Program (Radiation group) who underwent irradiation <=90 days before emergency surgery. Patients receiving concomitant chemotherapy were excluded. Subjects were compared to a Control group that did not have preoperative irradiation but underwent similar emergent procedures (matched 1:1 on age and procedure). Demographic and clinical characteristics, including patient co-morbidities, functional status, and preoperative laboratory values, were assessed. Primary outcomes included 30-day postoperative morbidity and mortality. Log-transformed data, bivariate and multivariate linear and conditional logistic regression were used. RESULTS: A total of 536 patients were included, 268 per group. Patient demographics and preoperative co-morbidities were similar between groups. The Radiation group had more mortality [23.9% vs. 11.6%, P < 0.001; odds ratio (OR) 2.4], major complications (45.1% vs. 34.7%, P = 0.014; OR 1.55), and a greater likelihood of sustaining a complication (48.1% vs. 38.1%, P = 0.019; OR 1.51). Days from admission to operation, operating time, likelihood of reoperation, days from operation to death, and length of hospital stay were not statistically different. By conditional logistic regression, death was independently associated with irradiation, chronic obstructive pulmonary disease (COPD), impaired preoperative functional status, and thrombocytopenia; and a major complication was associated with COPD, hypoalbuminemia, and preoperative wound infection. CONCLUSIONS: Patients who require emergent surgery <=90 days after irradiation sustain increased morbidity and mortality. Optimizing the nutritional and functional status of these patients may improve surgical outcomes. PMID- 22083434 TI - Risk factors for prolonged postoperative ileus after colorectal cancer surgery. AB - BACKGROUND: The aim of this study was to analyze factors contributing to prolonged postoperative ileus (POI) after elective bowel resection in patients with colorectal cancer. METHODS: This was a retrospective review of a prospectively maintained database of patients operated on for colorectal cancer during 2006-2009. Patients with abdominal procedures and bowel resection without anastomotic leakage were included. Prolonged POI was defined as no flatus by postoperative day (POD) 6, with or without intolerance to oral intake by POD 6. Variables studied included demographics, prior medical conditions, details of the surgical procedure, and hospital stay. RESULTS: A total of 773 patients met the inclusion criteria. POI occurred in 15.9%. The mean hospital stay was 11 days without POI and 20 days for POI patients (P < 0.001). Factors associated with POI in the univariate analysis were ASA III-IV (P < 0.005), male sex (P < 0.004), smoking (P < 0.015), chronic pulmonary disease (COPD) (P < 0.002), rectal cancer (P < 0.02), and ileostomy (P < 0.001). Multivariate logistic regression analysis showed male sex [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.04-3.5]; COPD (OR 1.9, 95% CI 1.25-31.0), and ileostomy (OR 1.9; 95% CI 1.23-3.07) as risk factors for POI. CONCLUSIONS: The risk of POI seems increased in patients with preoperative COPD and patients with an ileostomy, especially in men. Consideration of these factors could be important for the prevention and treatment of POI. PMID- 22083435 TI - Dexamethasone for prevention of postoperative nausea and vomiting in patients undergoing thyroidectomy: meta-analysis of randomized controlled trials. AB - BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication after thyroidectomy. Steroids effectively reduce nausea, pain, and inflammation; therefore, preoperative administration of steroids ought to improve these surgical outcomes. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) that compared preoperative single-dose administration of dexamethasone with no dexamethasone in patients undergoing thyroidectomy. The primary outcome was occurrence of PONV within 24 h, and the secondary outcomes were pain, use of analgesics, and steroid-related complications. RESULTS: Five RCTs were included with a total of 497 patients. A statistically and clinically significant difference in the incidence of PONV was found in favor of dexamethasone [relative risk (RR) 0.38; 95% confidence interval (CI) 0.30-0.49). The visual analog pain score was significantly diminished (weighted mean difference, WMD)-1.50; 95% CI-2.54 to -0.46) at 24 h. The incidence of analgesics use was also reduced (RR 0.61; 95% CI 0.41-0.90) in the dexamethasone group. No steroid-related complications were noted. CONCLUSIONS: A single preoperative administration of dexamethasone reduced the incidence of PONV and analgesic requirements in patients undergoing thyroidectomy. Prophylactic use of steroids for patients undergoing thyroidectomy is safe and should be considered for routine clinical practice. PMID- 22083436 TI - The importance of preoperative laryngeal examination before thyroidectomy and the usefulness of a voice questionnaire in screening. AB - BACKGROUND: The objectives of this study were to emphasize the importance of preoperative laryngeal examination before thyroidectomy by investigating the incidence of coincident abnormal laryngeal conditions that impair the quality of voice, and evaluate the usefulness of the "thyroidectomy-related voice questionnaire" as a screening tool. METHODS: Five hundred consecutive patients scheduled to undergo thyroidectomy underwent preoperative laryngeal examination and voice analysis and completed the questionnaire. According to the laryngeal examination results, patients were classified into normal and abnormal groups. Acoustic-analysis results and questionnaire scores were compared between the two groups, and correlations between acoustic parameters and questionnaire scores were evaluated. The cutoff score of the questionnaire that can effectively discriminate between the two groups was also determined. RESULTS: The incidence of abnormal laryngeal conditions was 35.8%. The most common finding was laryngopharyngeal reflux (27.2%) followed by vocal nodule (4.8%), vocal polyp (1.8%), vocal cord palsy (1.2%), Reinke's edema (0.4%), vocal cyst (0.2%), and vocal sulcus (0.2%). The perceptual grade of voice quality (0.33 +/- 0.49 for normal group vs. 0.65 +/- 0.62 for abnormal group, P = 0.000) and the questionnaire scores (3.21 +/- 5.47 for normal group vs. 13.41 +/- 11.67 for abnormal group, P = 0.000) of the two groups were significantly different, and there was a significant correlation between objective voice parameters and questionnaire scores. A questionnaire score of 5 showed the best sensitivity (74%) and specificity (71%) in discriminating between the two groups. CONCLUSIONS: The incidence of coincident abnormal laryngeal conditions is relatively high; therefore, voice screening before thyroidectomy is important. The "thyroidectomy-related voice questionnaire" is a simple and effective screening tool to detect preexisting laryngeal disorders that can affect the quality of voice. PMID- 22083437 TI - The prevalence and some metabolic traits of Brochothrix thermosphacta in meat and meat products packaged in different ways. AB - BACKGROUND: The effect of Brochothrix thermosphacta on the quality of meat and meat products is of vital importance in connection with Regulation EC/178/2002 extending the definition of unsafe foodstuffs to encompass all those which are unfit for human consumption. This study aimed to determine the prevalence of B. thermosphacta in meat and meat products packaged under different conditions and to estimate the effect of B. thermosphacta strains on product quality based on their protein and lipid degradation activity. RESULTS: B. thermosphacta was absent in only two of 132 samples. All other samples were contaminated with this bacterium (10(1) to 10(9) cfu g(-1) meat and 10(2) to 10(8) cfu g(-1) meat product). In products stored under high-oxygen atmosphere Brochothrix cells accounted for almost 100% total mesophilic count (TMC) and below 50% TMC in oxygen-free atmosphere. While the tested B. thermosphacta strains did not show any proteolytic activity, most of them displayed lipolytic activity at 25 degrees C and some even at 4 degrees C. CONCLUSION: B. thermosphacta is commonly present in meat and meat products packaged in different ways. This bacterium can display lipolytic activity also at refrigeration temperature. Its over proliferation can be inhibited through vacuum packaging or packaging under a modified atmosphere with reduced oxygen content. PMID- 22083438 TI - The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster. AB - Resveratrol, a polyphenolic compound, has been shown to extend lifespan in different organisms. Emerging evidence suggests that the prolongevity effect of resveratrol depends on dietary composition. However, the mechanisms underlying the interaction of resveratrol and dietary nutrients in modulating lifespan remain elusive. Here, we investigated the effect of resveratrol on lifespan of Drosophila melanogaster fed diets differing in the concentrations of sugar, yeast extract, and palmitic acid representing carbohydrate, protein, and fat, respectively. Resveratrol at up to 200 MUM in diets did not affect lifespan of wild-type female flies fed a standard, restricted or high sugar-low protein diet, but extended lifespan of females fed a low sugar-high protein diet. Resveratrol at 400 MUM extended lifespan of females fed a high-fat diet. Lifespan extension by resveratrol was associated with downregulation of genes in aging-related pathways, including antioxidant peroxiredoxins, insulin-like peptides involved in insulin-like signaling and several downstream genes in Jun-kinase signaling involved in oxidative stress response. Furthermore, resveratrol increased lifespan of superoxide dismutase 1 (sod1) knockdown mutant females fed a standard or high-fat diet. No lifespan extension by resveratrol was observed in wild-type and sod1 knockdown males under the culture conditions in this study. Our results suggest that the gender-specific prolongevity effect of resveratrol is influenced by dietary composition and resveratrol promotes the survival of flies by modulating genetic pathways that can reduce cellular damage. This study reveals the context-dependent effect of resveratrol on lifespan and suggests the importance of dietary nutrients in implementation of effective aging interventions using dietary supplements. PMID- 22083440 TI - Use of Self-Organizing Maps for Balanced Scorecard analysis to monitor the performance of dialysis clinic chains. AB - The Balanced Scorecard (BSC) is a validated tool to monitor enterprise performances against specific objectives. Through the choice and the evaluation of strategic Key Performance Indicators (KPIs), it provides a measure of the past company's outcome and allows planning future managerial strategies. The Fresenius Medical Care (FME) BSC makes use of 30 KPIs for a continuous quality improvement strategy within its dialysis clinics. Each KPI is monthly associated to a score that summarizes the clinic efficiency for that month. Standard statistical methods are currently used to analyze the BSC data and to give a comprehensive view of the corporate improvements to the top management. We herein propose the Self-Organizing Maps (SOMs) as an innovative approach to extrapolate information from the FME BSC data and to present it in an easy-readable informative form. A SOM is a computational technique that allows projecting high-dimensional datasets to a two-dimensional space (map), thus providing a compressed representation. The SOM unsupervised (self-organizing) training procedure results in a map that preserves similarity relations existing in the original dataset; in this way, the information contained in the high-dimensional space can be more easily visualized and understood. The present work demonstrates the effectiveness of the SOM approach in extracting useful information from the 30-dimensional BSC dataset: indeed, SOMs enabled both to highlight expected relationships between the KPIs and to uncover results not predictable with traditional analyses. Hence we suggest SOMs as a reliable complementary approach to the standard methods for BSC interpretation. PMID- 22083439 TI - A worldwide investigation of tuberculosis epidemics. AB - We analyse the tuberculosis (TB) epidemics of 211 countries with a view to proposing more efficient and targeted TB control strategies. Countries are classified by how their TB case notification rates have evolved over time and the age distribution of those suffering from active TB disease in 2008. Further analysis of key statistics associated with each of the countries shows the impact of different indicators. As expected, HIV is a key driver of TB epidemics and affects their age-distribution and their scale. The level of development of a country and its wealth also vary with the shape and scale of a country's TB epidemic. Immigration has an influence on the shape of TB epidemics, which is particularly pronounced in highly developed countries with low levels of TB disease in the native population. We conclude by proposing how the TB control programme in each country analysed should prioritise its efforts. PMID- 22083441 TI - Modelling human resources policies with Markov models: an illustration with the South African nursing labour market. AB - This article proposes a modelling framework to simulate and assess the immediate and long-term effects of policy interventions to attract and retain nurses in rural areas. Specifically, we use a Markov model to model the dynamics of movements of health care workers in a professional labour market. A model is developed to simulate the movements of South African nurses between different segments of the labour market over time. The model builds upon a series of assumptions that are stated in details, and uses predictions generated by discrete choice experiments. The results demonstrate the ability of Markov models to model the effects of human resources policy interventions in the short and long run. They highlight the effects of time on the effectiveness of some potential policy interventions, whose immediate positive effects can be eroded as different adverse effects appear. Despite its complexity, this innovative method provides a transparent and useful tool to inform the design of policies to address rural staff shortages. PMID- 22083444 TI - The Altemeier procedure using biologic mesh. AB - Transperineal rectosigmoidectomy is a relatively safe operation for the treatment of rectal prolapse; however, it carries a high rate of recurrence. The use of biologic mesh to buttress the repair and support the pelvic floor muscles may decrease the rate of recurrence. The technique for performing an Altemeier procedure with biologic mesh is described. PMID- 22083443 TI - Simple excision and closure of a distal limb of loop colostomy prolapse by stapler device. AB - Stomal prolapse is one of the common complications in transverse colostomy and can be managed conservatively in most cases; however, laparotomy and reconstruction of the stoma may sometimes be required, especially in case of irreducible colostomy prolapse. We have reported a simple local repair with reconstruction of the loop colostomy. We herein report a new more simple technique to avoid laparotomy and allow excision of the irreducible colostomy prolapse and complete closure of the distal limb of loop colostomy when no decompression is required in the distal limb of the stoma. In this procedure, the number of stapler and the time with blood loss for the operation can be saved. PMID- 22083445 TI - The state of the journal: a report to AJH readers, reviewers, and authors. PMID- 22083447 TI - NKCC1 as an epigenetically regulated transporter involved in blood pressure elevation with age. PMID- 22083448 TI - Rapid cortisol assay increases the success of adrenal vein sampling. PMID- 22083449 TI - Generation of accurate aortic pressure waves from calibrated upper limb pressure waveforms. PMID- 22083452 TI - Neuronal growth promoting sesquiterpene-neolignans; syntheses and biological studies. AB - The use of small molecules that can promote neuronal growth represents a promising approach to regenerative science. Along these lines we have developed separate short or modular syntheses of the natural products caryolanemagnolol and clovanemagnolol, small molecules previously shown to promote neuronal growth and induce choline acetyltransferase activity. The postulated biosynthetic pathways, potentially leading to the assembly of these molecules in nature, have guided the laboratory syntheses, allowing the preparation of both natural products in as few as two steps. With synthetic access to the compounds as single enantiomers we have examined clovanemagnolol's ability to promote the growth of embryonic hippocampal and cortical neurons. Clovanemagnolol has been shown to be a potent neurotrophic agent, promoting neuronal growth at concentrations of 10 nM. PMID- 22083453 TI - MRP1 expressed on Burkitt's lymphoma cells was depleted by catfish egg lectin through Gb3-glycosphingolipid and enhanced cytotoxic effect of drugs. AB - A novel anticancer mechanism of catfish (Silurus asotus) egg lectin (SAL) was found to occur via the down-regulation of the membrane transopter protein, MRP1 (multidrug resistance associate protein-1) on Burkitt's lymphoma cells through Gb3(Galalpha1-4Galbeta1-4Glc)-glycosphingolipid. Although SAL did not influence the viability of the cells directly, only 10 and 100 ng/mL of vincristine and etoposide, respectively induced anticancer effects when the lectin was applied in conjunction with these drugs. These phenomena were specifically inhibited by the co-presence of the alpha-galactoside, melibiose, which is a strong haptenic sugar of SAL that mimicks Gb3. The degree of expression regulation of the transporter proteins on the cells surface was investigated through the examination of the binding between SAL and Gb3-glycosphingolipid by immunological and molecular biological procedures. PCR data showed that MRP1 was more highly expressed when compared to another ATP-binding cassette family, multi-drug resistant protein and the expression levels of MRP1 on the cells were specifically dose- and time dependently depleted by the addition of SAL. These results were also evaluated by immunological procedures using FACS and western-blotting. Small interfering RNA coding a part of MRP1 was transfected to Raji cells to knock down the protein, and cell death was increased by 10% when vincristine was administered at a concentration as low as 10 ng/mL compared to non-transfected cells. These results indicated that SAL possesses the potential to enhance the anticancer activites of low-concentrations of vincristine by the down-regulating the MRP1 gene expression to inhibit the multidrug resistance by binding to the target ligand Gb3 glycosphingolipid on Burkitt's lymphoma cells. PMID- 22083454 TI - A study evaluating the effect of mifepristone (RU-486) for the treatment of leiomyomata uteri. AB - BACKGROUND: To estimate the efficacy of daily administration of 25 mg mifepristone for the treatment of uterine leiomyoma. MATERIALS AND METHODS: A total of 30 women were to receive 25 mg mifepristone daily for a period of 6 months. Abdominal ultrasonography was performed before treatment, at 3 months and after 6 months, to evaluate the leiomyoma size and uterine volume. Endometrial biopsy was done after the treatment. Efficacy was estimated by the reduction in leiomyoma size, uterine volume, and improvement in quality of life. RESULTS: After 180 days of treatment, there was a 47% decrease in the leiomyoma volume and a 53% decrease in the uterine volume. Symptomatic improvement was noted. Twenty three of 30 women (75.7%) became amenorrheic after the treatment. Endometrial biopsy after treatment revealed simple hyperplasia in two of 30 women. CONCLUSION: 25 mg mifepristone produces reduction in leiomyoma size and uterine volume and produces symptomatic improvement in women with fibroids. PMID- 22083455 TI - Single-step synthesis of pyrazoles using titanium catalysis. AB - A simple titanium complex catalyzes the coupling of alkynes, isonitriles, and monosubstituted hydrazines to generate substituted pyrazoles in a single step. PMID- 22083456 TI - Developing a provisional definition of flare in patients with established gout. AB - OBJECTIVE: Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. METHODS: Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. RESULTS: The mean +/- SD age of the study participants was 56.2 +/- 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (0-10 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). CONCLUSION: We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials. PMID- 22083458 TI - Cell cycle proteins in brain in mild cognitive impairment: insights into progression to Alzheimer disease. AB - Recent studies have demonstrated the re-emergence of cell cycle proteins in brain as patients progress from the early stages of mild cognitive impairment (MCI) into Alzheimer's disease (AD). Oxidative stress markers present in AD have also been shown to be present in MCI brain suggesting that these events occur in early stages of the disease. The levels of key cell cycle proteins, such as CDK2, CDK5, cyclin G1, and BRAC1 have all been found to be elevated in MCI brain compared to age-matched control. Further, peptidyl prolyl cis-trans isomerase (Pin1), a protein that plays an important role in regulating the activity of key proteins, such as CDK5, GSK3-beta, and PP2A that are involved in both the phosphorylation state of Tau and in the cell cycle, has been found to be oxidatively modified and downregulated in both AD and MCI brain. Hyperphosphorylation of Tau then results in synapse loss and the characteristic Tau aggregation as neurofibrillary tangles, an AD hallmark. In this review, we summarized the role of cell cycle dysregulation in the progression of disease from MCI to AD. Based on the current literature, it is tempting to speculate that a combination of oxidative stress and cell cycle dysfunction conceivably leads to neurodegeneration. PMID- 22083459 TI - Protective efficacy of coenzyme Q10 against DDVP-induced cognitive impairments and neurodegeneration in rats. AB - The present study was carried out to elucidate the effects of coenzyme Q(10) (CoQ(10)) against cognitive impairments induced by dichlorvos (DDVP). We have previously shown organophosphate, DDVP-induced impairments in neurobehavioral indices viz. rota rod, passive avoidance, and water maze tests. In addition to this, we have also reported that chronic DDVP exposure leads to decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I-III activity. Administration of CoQ(10) (4.5 mg/kg, i.p. for 12 weeks prior to DDVP administration daily) to DDVP-treated rats improved cognitive performance in passive avoidance task and Morris water maze test. Furthermore, CoQ(10) treatment also reduced oxidative stress (as evident by reduced malondialdehyde, decreased ROS and increased Mn-SOD activity) in DDVP treated rats' hippocampus region, along with enhanced activity of complexes I-III and complex IV. Electron microscope studies of rat hippocampus mitochondria revealed that CoQ(10) administration leads to near normal physiology of mitochondria with well-defined cristae compared with DDVP-treated animals where enlarged mitochondria with distorted cristae are observed. CoQ(10) administration also attenuated neuronal damage in hippocampus as evident from histopathological studies. These results demonstrate the beneficial effects of CoQ(10) against organophosphate-induced cognitive impairments and hippocampal neuronal degeneration. PMID- 22083462 TI - Nicking enzyme based homogeneous aptasensors for amplification detection of protein. AB - A simple and highly sensitive homogeneous aptasensor is developed, which relies on nicking enzyme. The sensitivity of this newly proposed aptasensor is about three orders of magnitude higher than that of traditional homogeneous aptasensors. Furthermore, it is capable of detecting target protein in real samples. PMID- 22083460 TI - Common pathways of autoimmune inflammatory myopathies and genetic neuromuscular disorders. AB - It has been shown that many hereditary motor neuron diseases are caused by mutation of RNA processing enzymes. Survival of motor neuron 1 (SMN1) is well known as a causative gene for spinal muscular atrophy (SMA) and mutations of glycyl- and tyrosyl-tRNA synthetases are identified as a cause of distal SMA and Charcot-Marie-Tooth disease. Why and how the dysfunction of these ubiquitously expressed genes involved in RNA processing can cause a specific neurological disorder is not well understood. Interestingly, SMN complex has been identified recently as a new target of autoantibodies in polymyositis (PM). Autoantibodies in systemic rheumatic diseases are clinically useful biomarkers associated with a particular diagnosis, subset of a disease, or certain clinical characteristics. Many autoantibodies produced in patients with polymyositis/dermatomyositis (PM/DM) target RNA-protein complexes such as aminoacyl tRNA synthetases. It is interesting to note these same RNA-protein complexes recognized by autoantibodies in PM/DM are also responsible for genetic neuromuscular disease. Certain RNA protein complexes are also targets of autoantibodies in paraneoplastic neurological disorders. Thus, there are several interesting associations between RNA-processing enzymes and neuromuscular disorders. Although pathogenetic roles of autoantibodies to intracellular antigens are generally considered unlikely, understanding the mechanisms of antigen selection in a particular disease and specific neurological symptoms caused by disruption of ubiquitous RNA-processing enzyme may help identify a common path in genetic neuromuscular disorders and autoimmunity in inflammatory myopathies. PMID- 22083463 TI - Fasciae anatomy. PMID- 22083464 TI - The strength to cope: spirituality and faith in chronic disease. AB - The lifelong management of a chronic condition requires considerable mental fortitude and commitment in social adjustment and adherence to medical advice. In examining strategies of adaptation, we draw on ethnographic research, including interviews with 69 people with type 2 diabetes and/or cardiovascular disease. We explore how they incorporate spirituality into their self-management routines, with positive impact on their health and wellbeing, and highlight the role of spiritual practices in supporting people with chronic conditions mentally, physically and socially, so encouraging personal responsibility for one's health and wellbeing. PMID- 22083465 TI - Genetic features of the widespread plasmid coding for the carbapenemase OXA-48. AB - Complete sequencing of plasmid pOXA-48a carrying the bla(OXA-48) gene from a Klebsiella pneumoniae isolate was performed. Its backbone corresponded to that of an IncL/M-type plasmid, in which the bla(OXA-48) gene had been integrated through the acquisition of the Tn1999 composite transposon without any other antibiotic resistance gene. Molecular epidemiology using a collection of international OXA 48 producers revealed the wide diffusion of pOXA-48a or closely related plasmids. PMID- 22083466 TI - Penetration of doripenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers. AB - Sufficient antibiotic concentrations at the infection site are a prerequisite for good bacterial killing. This study was performed to determine pharmacokinetics of doripenem in soft tissues and saliva. Six healthy male volunteers received a single intravenous infusion of 500 mg doripenem over 1 h. The concentrations of doripenem were measured over 8 h in saliva, plasma, and extracellular space fluid of skeletal muscle and subcutaneous adipose tissue employing in vivo microdialysis. Unbound drug concentrations were determined using ultra-high performance liquid chromatography-tandem mass spectrometry. Maximum concentrations of doripenem were 15.3 +/- 6.0 mg/liter in plasma, 9.9 +/- 2.3 mg/liter in subcutaneous adipose tissue, 6.6 +/- 2.9 mg/liter in skeletal muscle, and 0.5 +/- 0.2 mg/liter in saliva. Areas under the concentration-time curve (AUC) from 0 to infinity were 26.3 +/- 10.1, 20.4 +/- 3.8, 12.8 +/- 3.0, and 1.0 +/- 0.5 mg . h/liter in plasma, adipose tissue, skeletal muscle, and saliva, respectively. Ratios of AUC in adipose tissue, skeletal muscle, and saliva to those in plasma were 0.84 +/- 0.28, 0.53 +/- 0.19, and 0.04 +/- 0.03, respectively. In all six volunteers, a threshold of >=40% for "time above MIC," an index indicative of good antimicrobial activity, was exceeded in adipose tissue for MICs of <=2 mg/liter and in skeletal muscle for MICs <=1.5 mg/liter. Doripenem penetrates well into interstitial space fluid of skeletal muscle and adipose tissue, suggesting good antimicrobial activity in infected soft tissues, whereas it is detectable in relatively low concentrations in saliva. PMID- 22083467 TI - Phenotypic and genotypic analysis of in vitro-selected artemisinin-resistant progeny of Plasmodium falciparum. AB - Emergence of artemisinin resistance in Cambodia highlights the importance of characterizing resistance to this class of drugs. Previously, intermediate levels of resistance in Plasmodium falciparum were generated in vitro for artelinic acid (AL) and artemisinin (QHS). Here we expanded on earlier selection efforts to produce levels of clinically relevant concentrations, and the resulting lines were characterized genotypically and phenotypically. Recrudescence assays determined the ability of resistant and parent lines to recover following exposure to clinically relevant levels of drugs. Interestingly, the parent clone (D6) tolerated up to 1,500 ng/ml QHS, but the resistant parasite, D6.QHS340*3, recovered following exposure to 2,400 ng/ml QHS. Resistant D6, W2, and TM91c235 parasites all exhibited elevated 50% inhibitory concentrations (IC(50)s) to multiple artemisinin drugs, with >3-fold resistance to QHS and AL; however, the degree of resistance obtained with standard methods was remarkably less than expected for parasite lines that recovered from 2,400-ng/ml drug pressure. A novel assay format with radiolabeled hypoxanthine demonstrated a greater degree of resistance in vitro than the standard SYBR green method. Analysis of merozoite number in resistant parasites found D6 and TM91c235 resistant progeny had significantly fewer merozoites than parent strains, whereas W2 resistant progeny had significantly more. Amplification of pfmdr1 increased proportionately to the increased drug levels tolerated by W2 and TM91c235, but not in resistant D6. In summary, we define the artemisinin resistance phenotype as a decrease in susceptibility to artemisinins along with the ability to recover from drug induced dormancy following supraclinical concentrations of the drug. PMID- 22083468 TI - PD 404,182 is a virocidal small molecule that disrupts hepatitis C virus and human immunodeficiency virus. AB - We describe a virucidal small molecule, PD 404,182, that is effective against hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The median 50% inhibitory concentrations (IC(50)s) for the antiviral effect of PD 404,182 against HCV and HIV in cell culture are 11 and 1 MUM, respectively. The antiviral activity of PD 404,182 is due to the physical disruption of virions that is accompanied to various degrees (depending on the virus and exposure temperature/time) by the release of viral nucleic acids into the surrounding medium. PD 404,182 does not directly lyse liposomal membranes even after extended exposure, and it shows no attenuation in antiviral activity when preincubated with liposomes of various lipid compositions, suggesting that the compound inactivates viruses through interaction with a nonlipid structural component of the virus. The virucidal activity of PD 404,182 appears to be virus specific, as little to no viral inactivation was detected with the enveloped Dengue and Sindbis viruses. PD 404,182 effectively inactivates a broad range of primary isolates of HIV-1 as well as HIV-2 and simian immunodeficiency virus (SIV), and it does not exhibit significant cytotoxicity with multiple human cell lines in vitro (50% cytotoxic concentration, >300 MUM). The compound is fully active in cervical fluids, although it exhibits decreased potency in the presence of human serum, retains its full antiviral potency for 8 h when in contact with cells, and is effective against both cell-free and cell-associated HIV. These qualities make PD 404,182 an attractive candidate anti-HIV microbicide for the prevention of HIV transmission through sexual intercourse. PMID- 22083469 TI - Activities of E1210 and comparator agents tested by CLSI and EUCAST broth microdilution methods against Fusarium and Scedosporium species identified using molecular methods. AB - Fusarium (n = 67) and Scedosporium (n = 63) clinical isolates were tested by two reference broth microdilution (BMD) methods against a novel broad-spectrum (active against both yeasts and molds) antifungal, E1210, and comparator agents. E1210 inhibits the inositol acylation step in glycophosphatidylinositol (GPI) biosynthesis, resulting in defects in fungal cell wall biosynthesis. Five species complex organisms/species of Fusarium (4 isolates unspeciated) and 28 Scedosporium apiospermum, 7 Scedosporium aurantiacum, and 28 Scedosporium prolificans species were identified by molecular techniques. Comparator antifungal agents included anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B. E1210 was highly active against all of the tested isolates, with minimum effective concentration (MEC)/MIC(90) values (MUg/ml) for E1210, anidulafungin, caspofungin, itraconazole, posaconazole, voriconazole, and amphotericin B, respectively, for Fusarium of 0.12, >16, >16, >8, >8, 8, and 4 MUg/ml. E1210 was very potent against the Scedosporium spp. tested. The E1210 MEC(90) was 0.12 MUg/ml for S. apiospermum, but 1 to >8 MUg/ml for other tested agents. Against S. aurantiacum, the MEC(50) for E1210 was 0.06 MUg/ml versus 0.5 to >8 MUg/ml for the comparators. Against S. prolificans, the MEC(90) for E1210 was only 0.12 MUg/ml, compared to >4 MUg/ml for amphotericin B and >8 MUg/ml for itraconazole, posaconazole, and voriconazole. Both CLSI and EUCAST methods were highly concordant for E1210 and all comparator agents. The essential agreement (EA; +/-2 doubling dilutions) was >93% for all comparisons, with the exception of posaconazole and F. oxysporum species complex (SC) (60%), posaconazole and S. aurantiacum (85.7%), and voriconazole and S. aurantiacum (85.7%). In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either of the CLSI or EUCAST BMD methods, each producing very similar results. PMID- 22083470 TI - Characterization of CIA-1, an Ambler class A extended-spectrum beta-lactamase from Chryseobacterium indologenes. AB - An Ambler class A beta-lactamase gene, bla(CIA-1), was cloned from the reference strain Chryseobacterium indologenes ATCC 29897 and expressed in Escherichia coli BL21. The bla(CIA-1) gene encodes a novel extended-spectrum beta-lactamase (ESBL) that shared 68% and 60% identities with the CGA-1 and CME-1 beta-lactamases, respectively. bla(CIA-1)-like genes were detected from clinical isolates. In addition to the metallo-beta-lactamase IND of Ambler class B, C. indologenes has a class A ESBL gene, bla(CIA-1), located on the chromosome. PMID- 22083471 TI - Population pharmacokinetics of liposomal amphotericin B and caspofungin in allogeneic hematopoietic stem cell recipients. AB - Liposomal amphotericin B (LAMB) and caspofungin (CAS) are important antifungal agents in allogeneic hematopoietic stem cell transplant (aHSCT) recipients. Little is known, however, about the pharmacokinetics (PK) of both agents and their combination in this population. The PK of LAMB and CAS and the potential for PK interactions between both agents were investigated within a risk stratified, randomized phase II clinical trial in 53 adult aHSCT recipients with granulocytopenia and refractory fever. Patients received either LAMB (n = 17; 3 mg/kg once a day [QD]), CAS (n = 19; 50 mg QD; day 1, 70 mg), or the combination of both (CAS-LAMB; n = 17) for a median duration of 10 to 13 days (range, 4 to 28 days) until defervescence and granulocyte recovery. PK sampling was performed on days 1 and 4. Drug concentrations in plasma (LAMB, 405 samples; CAS, 458 samples) were quantified by high-pressure liquid chromatography and were analyzed using population pharmacokinetic modeling. CAS concentration data best fitted a two compartment model with a proportional error model and interindividual variability (IIV) for clearance (CL) and central volume of distribution (V(1)) (CL, 0.462 liter/h +/- 25%; V(1), 8.33 liters +/- 29%; intercompartmental clearance [Q], 1.25 liters/h; peripheral volume of distribution [V(2)], 3.59 liters). Concentration data for LAMB best fitted a two-compartment model with a proportional error model and IIV for all parameters (CL, 1.22 liters/h +/- 64%; V(1), 19.2 liters +/- 38%; Q, 2.18 liters/h +/- 47%; V(2), 52.8 liters +/- 84%). Internal model validation showed predictability and robustness of both models. None of the covariates tested (LAMB or CAS comedication, gender, body weight, age, body surface area, serum bilirubin, and creatinine clearance) further improved the models. In summary, the disposition of LAMB and CAS was best described by two-compartment models. Drug exposures in aHSCT patients were comparable to those in other populations, and no PK interactions were observed between the two compounds. PMID- 22083472 TI - In vitro activities of candidate microbicides against cell-associated HIV. AB - Most research on HIV transmission and microbicides focuses on the inhibition of cell-free virus (CFV) present in genital secretions. However, an effective microbicide should also block the transmission of cell-associated virus (CAV) originating from seminal T cells and macrophages. Because inhibition of CAV remains controversial, especially for viral entry inhibitors, we developed a novel in vitro assay to evaluate the activities of different classes of candidate microbicides against cell-free HIV and HIV-infected leukocytes (i.e., resting peripheral blood mononuclear cells [PBMC], activated PBMC, and monocyte-derived macrophages). The assay is based on two CD4(+) CXCR4(+) T-cell lines (R5MaRBLE and X4MaRBLE) that both contain a firefly luciferase reporter gene but differ in the expression of the CCR5 coreceptor. Consequently, the quantification of the luciferase activities and the Gag p24 concentrations in cocultures of R5-tropic HIV-infected leukocytes with each cell line separately allowed us to discriminate between the infection of the cell lines (i.e., target cells), the ongoing infection in the HIV-infected leukocytes (i.e., effector cells), and the total infection of the coculture (i.e., effector plus target cells). All 14 antiretrovirals tested were able to block target cell infection by all three sources of CAV, although a small decrease in activity (2- to 18-fold) was observed for all entry inhibitors. On the other hand, the production of Gag p24 by the infected effector cells could be blocked only by protease inhibitors. Overall, these results show that entry and protease inhibitors are eligible drug classes for inclusion in future combination microbicides. PMID- 22083473 TI - Ertapenem pharmacokinetics and pharmacodynamics during continuous ambulatory peritoneal dialysis. AB - Scant data exist for the pharmacokinetics (PK) of ertapenem in patients on continuous ambulatory peritoneal dialysis (CAPD). The goals of this study were to characterize the PK profile of ertapenem during CAPD, determine the extent of ertapenem penetration into the peritoneal cavity, and quantify the probability of the target attainment (PTA) profile in the serum and peritoneal cavity. A single dose PK study was conducted in seven patients on CAPD. Population PK modeling and Monte Carlo simulation determined the probability that ertapenem at 500 mg intravenously (i.v.) every 24 h (q24h) would achieve concentrations in excess of the MIC for 40% of the dosing interval (40% T>MIC, where T is time) in the serum and peritoneal cavity. Monte Carlo simulation was also used to calculate the peritoneal cavity/serum mean and median penetration ratios by estimating the area under the concentration-time curve in the peritoneal cavity and serum (AUC(Peritoneal) and AUC(Serum), respectively) from zero to infinity after a single simulated dose. The population mean (+/- standard deviation [SD]) values for the apparent volume in the central compartment, clearance, and apparent volume in the peritoneal cavity were 2.78 (0.62) liters, 0.24 (0.07) liters/hr, and 5.81 (2.05) liters, respectively. The mean (SD) AUC(Peritoneal)/AUC(Serum) ratio was 1.039 (0.861), and the median penetration ratio was 0.801 (interquartile range, 0.486 to 1.317). In both the serum and peritoneal cavity, ertapenem at 500 mg i.v. q24h was very likely (>90%) to achieve the pharmacodynamic target for MICs of <=2 mg/liter. The simulations suggest that 500 mg of ertapenem i.v. q24h is very likely to achieve the exposure target associated with clinical efficacy in both the serum and peritoneal cavity against the range of MIC values deemed susceptible by the Clinical and Laboratory Standards Institute. PMID- 22083474 TI - Inactivation of the lipopeptide antibiotic daptomycin by hydrolytic mechanisms. AB - The lipopeptide daptomycin is a member of the newest FDA-approved antimicrobial class, exhibiting potency against a broad range of Gram-positive pathogens with only rare incidences of clinical resistance. Environmental bacteria harbor an abundance of resistance determinants orthologous to those in pathogens and thus may serve as an early-warning system for future clinical emergence. A collection of morphologically diverse environmental actinomycetes demonstrating unprecedented frequencies of daptomycin resistance and high levels of resistance by antibiotic inactivation was characterized to elucidate modes of drug inactivation. In vivo studies revealed that hydrolysis plays a key role, resulting in one or both of the following structural modifications: ring hydrolysis resulting in linearization (in 44% of inactivating isolates) or deacylation of the lipid tail (29%). Characterization of the mechanism in actinomycete WAC4713 (a Streptomyces sp. with an MIC of 512 MUg/ml) demonstrated a constitutive resistance phenotype and established daptomycin's circularizing ester linkage to be the site of hydrolysis. Characterization of the hydrolase responsible revealed it to be likely a serine protease. These studies suggested that daptomycin is susceptible to general proteolytic hydrolysis, which was further supported by studies using proteases of diverse origin. These findings represent the first comprehensive characterization of daptomycin inactivation in any bacterial class and may not only presage a future mechanism of clinical resistance but also suggest strategies for the development of new lipopeptides. PMID- 22083475 TI - In vitro and in vivo activity of solithromycin (CEM-101) against Plasmodium species. AB - With the emergence of Plasmodium falciparum infections exhibiting increased parasite clearance times in response to treatment with artemisinin-based combination therapies, the need for new therapeutic agents is urgent. Solithromycin, a potent new fluoroketolide currently in development, has been shown to be an effective, broad-spectrum antimicrobial agent. Malarial parasites possess an unusual organelle, termed the apicoplast, which carries a cryptic genome of prokaryotic origin that encodes its own translation and transcription machinery. Given the similarity of apicoplast and bacterial ribosomes, we have examined solithromycin for antimalarial activity. Other antibiotics known to target the apicoplast, such as the macrolide azithromycin, demonstrate a delayed death effect, whereby treated asexual blood-stage parasites die in the second generation of drug exposure. Solithromycin demonstrated potent in vitro activity against the NF54 strain of P. falciparum, as well as against two multidrug resistant strains, Dd2 and 7G8. The dramatic increase in potency observed after two generations of exposure suggests that it targets the apicoplast. Solithromycin also retained potency against azithromycin-resistant parasites derived from Dd2 and 7G8, although these lines did demonstrate a degree of cross resistance. In an in vivo model of P. berghei infection in mice, solithromycin demonstrated a 100% cure rate when administered as a dosage regimen of four doses of 100 mg/kg of body weight, the same dose required for artesunate or chloroquine to achieve 100% cure rates in this rodent malaria model. These promising in vitro and in vivo data support further investigations into the development of solithromycin as an antimalarial agent. PMID- 22083476 TI - Characterization of the inhibitor-resistant SHV beta-lactamase SHV-107 in a clinical Klebsiella pneumoniae strain coproducing GES-7 enzyme. AB - The clinical Klebsiella pneumoniae INSRA6884 strain exhibited nonsusceptibility to all penicillins tested (MICs of 64 to >2,048 MUg/ml). The MICs of penicillins were weakly reduced by clavulanate (from 2,048 to 512 MUg/ml), and tazobactam restored piperacillin susceptibility. Molecular characterization identified the genes bla(GES-7) and a new beta-lactamase gene, bla(SHV-107), which encoded an enzyme that differed from SHV-1 by the amino acid substitutions Leu35Gln and Thr235Ala. The SHV-107-producing Escherichia coli strain exhibited only a beta lactam resistance phenotype with respect to amoxicillin, ticarcillin, and amoxicillin-clavulanate combination. The kinetic parameters of the purified SHV 107 enzyme revealed a high affinity for penicillins. However, catalytic efficiency for these antibiotics was lower for SHV-107 than for SHV-1. No hydrolysis was detected against oxyimino-beta-lactams. The 50% inhibitory concentration (IC(50)) for clavulanic acid was 9-fold higher for SHV-107 than for SHV-1, but the inhibitory effects of tazobactam were unchanged. Molecular dynamics simulation suggested that the Thr235Ala substitution affects the accommodation of clavulanate in the binding site and therefore its inhibitory activity. PMID- 22083477 TI - Blood, tissue, and intracellular concentrations of erythromycin and its metabolite anhydroerythromycin during and after therapy. AB - For macrolides, clinical activity but also the development of bacterial resistance has been attributed to prolonged therapeutic and subtherapeutic concentrations. Although erythromycin is a long-established antimicrobial, concomitant determination of the pharmacokinetics of erythromycin and its metabolites in different compartments is limited. To better characterize the pharmacokinetics of erythromycin and its anhydrometabolite (anhydroerythromycin [AHE]) in different compartments during and after the end of treatment with 500 mg of erythromycin four times daily, concentration-time profiles were determined in plasma, interstitial space of muscle and subcutaneous adipose tissue, and white blood cells (WBCs) at days 1 and 3 of treatment and 2 and 7 days after end of therapy. In WBCs, concentrations of erythromycin exceeded those in plasma approximately 40-fold, while free concentrations in plasma and tissue were comparable. The observed delay of peak concentrations in tissue might be caused by fast initial cellular uptake. Two days after the end of treatment, subinhibitory concentrations were observed in plasma and interstitial space of both soft tissues, while 7 days after the end of treatment, erythromycin was not detectable in any compartment. This relatively short period of subinhibitory concentrations may be advantageous compared to other macrolides. The ratio of erythromycin over AHE on day 1 was highest in plasma (2.81 +/- 3.45) and lowest in WBCs (0.27 +/- 0.22). While the ratio remained constant between single dose and steady state, after the end of treatment the concentration of AHE declined more slowly than that of the parent compound, indicating the importance of the metabolite for the prolonged drug interaction of erythromycin. PMID- 22083478 TI - Emergence of carbapenem-resistant non-baumannii species of Acinetobacter harboring a blaOXA-51-like gene that is intrinsic to A. baumannii. AB - The bla(OXA-51)-like gene, originally intrinsic to Acinetobacter baumannii, had been detected in two clones of Acinetobacter nosocomialis and one clone of Acinetobacter genomic species "Close to 13TU." These bla(OXA-51)-like genes, all preceded by ISAba1, were located on plasmids that might have originated with A. baumannii. The plasmid-borne ISAba1--bla(OXA-51)-like confers a high level of carbapenem resistance and affects the accuracy of using bla(OXA-51)-like detection as a tool for differentiating A. baumannii from other Acinetobacter species. PMID- 22083479 TI - Decoding the functional roles of cationic side chains of the major antimicrobial region of human cathelicidin LL-37. AB - Human cathelicidin LL-37 is a critical cationic antimicrobial peptide for host defense against infection, immune modulation, and wound healing. This article elucidates the functional roles of the cationic side chains of the major antimicrobial region of LL-37, corresponding to residues 17 to 32 (designated GF 17). Antimicrobial assays, killing kinetics studies, and vesicle leakage experiments all indicate that a conversion of lysines to arginines affected the ability of the peptide to kill the Gram-positive Staphylococcus aureus strain USA300. Alanine scanning experiments show that S. aureus is less sensitive than Escherichia coli to a single cationic residue mutation of GF-17. Among the five cationic residues, R23 appears to be somewhat important in killing S. aureus. However, R23 and K25 of GF-17 are of prime importance in killing the Gram negative organism E. coli. In particular, R23 is essential for (i) rapid recognition, (ii) permeation of the E. coli outer membrane, (iii) clustering of anionic lipids in a membrane system mimicking the E. coli inner membrane, and (iv) membrane disruption. Bacterial aggregation (i.e., rapid recognition via charge neutralization) is the first step of the peptide action. Structurally, R23 is located in the interface (i.e., the first action layer), a situation ideal for the interactions listed above. In contrast, residues K18, R19, and R29 are on the hydrophilic surface of the amphipathic helix and play only a secondary role. Mapping of the functional spectrum of cationic residues of GF-17 provides a solid basis for engineering bacterium-specific antimicrobials using this highly potent template. PMID- 22083480 TI - Characterization of the inhibition mechanism of HIV-1 nucleocapsid protein chaperone activities by methylated oligoribonucleotides. AB - Since currently available therapies against HIV/AIDS still show important drawbacks, the development of novel anti-HIV treatments is a key issue. We recently characterized methylated oligoribonucleotides (mONs) that extensively inhibit HIV-1 replication in primary T cells at nanomolar concentrations. The mONs were shown to target both HIV-1 reverse transcriptase (RT) and the nucleocapsid protein (NC), which is an essential partner of RT during viral DNA synthesis. To further understand the mechanism of such mONs, we studied by isothermal titration calorimetry and fluorescence-based techniques their NC binding properties and ability to inhibit the nucleic acid chaperone properties of NC. Notably, we investigated the ability of mONs to inhibit the NC-induced destabilization of the HIV-1 cTAR (complementary DNA sequence to TAR [transactivation response element]) stem-loop and the NC-promoted cTAR annealing to its complementary sequence, required at the early stage of HIV-1 viral DNA synthesis. Moreover, we compared the activity of the mONs to that of a number of modified and nonmodified oligonucleotides. Results show that the mONs inhibit NC by a competitive mechanism whereby the mONs tightly bind the NC peptide, mainly through nonelectrostatic interactions with the hydrophobic platform at the top of the NC zinc fingers. Taken together, these results favor the notion that the mONs impair the process of the RT-directed viral DNA synthesis by sequestering NC molecules, thus preventing the chaperoning of viral DNA synthesis by NC. These findings contribute to the understanding of the molecular basis for NC inhibition by mONs, which could be used for the rational design of antiretroviral compounds targeting HIV-1 NC protein. PMID- 22083482 TI - Effects of Melaleuca alternifolia (tea tree) essential oil and the major monoterpene component terpinen-4-ol on the development of single- and multistep antibiotic resistance and antimicrobial susceptibility. AB - This study examined the effect of subinhibitory Melaleuca alternifolia (tea tree) essential oil on the development of antibiotic resistance in Staphylococcus aureus and Escherichia coli. Frequencies of single-step antibiotic-resistant mutants were determined by inoculating bacteria cultured with or without subinhibitory tea tree oil onto agar containing 2 to 8 times the MIC of each antibiotic and with or without tea tree oil. Whereas most differences in resistance frequencies were relatively minor, the combination of kanamycin and tea tree oil yielded approximately 10-fold fewer resistant E. coli mutants than kanamycin alone. The development of multistep antibiotic resistance in the presence of tea tree oil or terpinen-4-ol was examined by culturing S. aureus and E. coli isolates daily with antibiotic alone, antibiotic with tea tree oil, and antibiotic with terpinen-4-ol for 6 days. Median MICs for each antibiotic alone increased 4- to 16-fold by day 6. Subinhibitory tea tree oil or terpinen-4-ol did not greatly alter results, with day 6 median MICs being either the same as or one concentration different from those for antibiotic alone. For tea tree oil and terpinen-4-ol alone, day 6 median MICs had increased 4-fold for S. aureus (n = 18) and 2-fold for E. coli (n = 18) from baseline values. Lastly, few significant changes in antimicrobial susceptibility were seen for S. aureus and S. epidermidis isolates that had been serially subcultured 14 to 22 times with subinhibitory terpinen-4-ol. Overall, these data indicate that tea tree oil and terpinen-4-ol have little impact on the development of antimicrobial resistance and susceptibility. PMID- 22083481 TI - Antiviral breadth and combination potential of peptide triazole HIV-1 entry inhibitors. AB - The first stage of human immunodeficiency virus type 1 (HIV-1) infection involves the fusion of viral and host cellular membranes mediated by viral envelope glycoprotein gp120. Inhibitors that specifically target gp120 are gaining increased attention as therapeutics or preventatives to prevent the spread of HIV 1. One promising new group of inhibitors is the peptide triazoles, which bind to gp120 and simultaneously block its interaction with both CD4 and the coreceptor. In this study, we assessed the most potent peptide triazole, HNG-156, for inhibitory breadth, cytotoxicity, and efficacy, both alone and in combination with other antiviral compounds, against HIV-1. HNG-156 inhibited a panel of 16 subtype B and C isolates of HIV-1 in a single-round infection assay. Inhibition of cell infection by replication-competent clinical isolates of HIV-1 was also observed with HNG-156. We found that HNG-156 had a greater than predicted effect when combined with several other entry inhibitors or the reverse transcriptase inhibitor tenofovir. Overall, we find that HNG-156 is noncytotoxic, has a broad inhibition profile, and provides a positive combination with several inhibitors of the HIV-1 life cycle. These results support the pursuit of efficacy and toxicity analyses in more advanced cell and animal models to develop peptide triazole family inhibitors of HIV-1 into antagonists of HIV-1 infection. PMID- 22083483 TI - Yersinia pestis AcrAB-TolC in antibiotic resistance and virulence. AB - The efflux pump AcrAB is important in the antibiotic resistance and virulence of several pathogenic bacteria. We report that deletion of the Yersinia pestis AcrAB TolC homolog leads to increased susceptibility to diverse substrates, including, though unlike in Escherichia coli, the aminoglycosides. Neither is the Y. pestis pump affected by the efflux pump inhibitor phenylalanine-arginine beta naphthylamide. In mouse plague models, pump deletion does not have a significant effect on tissue colonization. PMID- 22083484 TI - Evaluation of once-daily vancomycin against methicillin-resistant Staphylococcus aureus in a hollow-fiber infection model. AB - For methicillin-resistant Staphylococcus aureus (MRSA) infections, data suggest that the clinical response is significantly better if the total vancomycin area under the concentration-time curve (AUC)/MIC ratio is >=400. While the AUC/MIC ratio is the accepted pharmacokinetic/pharmacodynamic (PK/PD) index for vancomycin, this target has been achieved using multiple daily doses. We are unaware of a systematically designed dose fractionation study to compare the bactericidal activity of once-daily administration to that of traditional twice daily administration. A dose fractionation study was performed with vancomycin in an in vitro hollow-fiber infection model against an MRSA USA300 strain (MIC of 0.75 MUg/ml) using an inoculum of ~10(6) CFU/ml. The three vancomycin regimens evaluated for 168 h were 2 g every 24 h (q24h) as a 1-h infusion, 1 g q12h as a 1 h infusion, and 2 g q24h as a continuous infusion. Free steady-state concentrations (assuming 45% binding) for a total daily AUC/MIC ratio of >=400 were simulated for all regimens. A validated liquid chromatography-tandem mass spectrometry method was used to determine vancomycin concentrations. Although once-daily and twice-daily dosage regimens exhibited total trough concentrations of <15 MUg/ml, all regimens achieved similar bactericidal activities between 24 and 168 h and suppressed the amplification of nonsusceptible subpopulations. No colonies were found on agar plates with 3* MIC for any of the treatment arms. Overall, the results suggest that once-daily vancomycin administration is feasible from a PK/PD perspective and merits further inquiry in the clinical arena. PMID- 22083485 TI - Prospective investigation of nasal mupirocin, hexachlorophene body wash, and systemic antibiotics for prevention of recurrent community-associated methicillin resistant Staphylococcus aureus infections. AB - Recurrent community-associated methicillin-resistant Staphylococcus aureus (CA MRSA) skin infections are an increasingly common problem. However, there are no data on the efficacy of decolonization regimens. We prospectively evaluated 31 patients with recurrent CA-MRSA skin infections who received nasal mupirocin, topical hexachlorophene body wash, and an oral anti-MRSA antibiotic. The mean number of MRSA infections after the intervention decreased significantly from baseline (0.03 versus 0.84 infections/month, P = <0.0001). This regimen appears promising at preventing recurrent CA-MRSA infections. PMID- 22083486 TI - Micafungin concentrations in the plasma and burn eschar of severely burned patients. AB - Micafungin concentrations in plasma and burn eschar after daily intravenous infusion (1 h) of micafungin (200 to 300 mg) were investigated for six patients with severe burns. Micafungin treatment was initiated more than 72 h after the burn injuries. The peak and trough levels in the plasma after the initial administration and repeated administrations for more than 4 days were comparable with or slightly lower than the reported values for healthy volunteers. Micafungin concentrations in the plasma and burn eschar were between 3.6 and >1,000 times higher than the reported MIC(90)s of micafungin against clinically important Candida and Aspergillus species. PMID- 22083487 TI - Complete sequence of broad-host-range plasmid pRIO-5 harboring the extended spectrum-beta-lactamase gene blaBES-1. AB - Broad-host-range plasmid pRIO-5, harboring the extended-spectrum beta-lactamase bla(BES-1) gene in Serratia marcescens, was fully sequenced. Analysis of the 12,957-bp sequence of this IncP6-type plasmid revealed that the bla(BES-1) gene was associated with two copies of the insertion sequence IS26. The promoter responsible for the bla(BES-1) expression was hybrid, made of a -35 box located inside the inverted repeat of IS26 and a -10 box inside a remnant of an insertion sequence. PMID- 22083488 TI - Interplay between single resistance-associated mutations in the HIV-1 protease and viral infectivity, protease activity, and inhibitor sensitivity. AB - Resistance-associated mutations in the HIV-1 protease modify viral fitness through changes in the catalytic activity and altered binding affinity for substrates and inhibitors. In this report, we examine the effects of 31 mutations at 26 amino acid positions in protease to determine their impact on infectivity and protease inhibitor sensitivity. We found that primary resistance mutations individually decrease fitness and generally increase sensitivity to protease inhibitors, indicating that reduced virion-associated protease activity reduces virion infectivity and the reduced level of per virion protease activity is then more easily titrated by a protease inhibitor. Conversely, mutations at more variable positions (compensatory mutations) confer low-level decreases in sensitivity to all protease inhibitors with little effect on infectivity. We found significant differences in the observed effect on infectivity with a pseudotype virus assay that requires the protease to cleave the cytoplasmic tail of the amphotropic murine leukemia virus (MuLV) Env protein. Additionally, we were able to mimic the fitness loss associated with resistance mutations by directly reducing the level of virion-associated protease activity. Virions containing 50% of a D25A mutant protease were 3- to 5-fold more sensitive to protease inhibitors. This level of reduction in protease activity also resulted in a 2-fold increase in sensitivity to nonnucleoside inhibitors of reverse transcriptase and a similar increase in sensitivity to zidovudine (AZT), indicating a pleiotropic effect associated with reduced protease activity. These results highlight the interplay between enzyme activity, viral fitness, and inhibitor mechanism and sensitivity in the closed system of the viral replication complex. PMID- 22083489 TI - The class A beta-lactamase FTU-1 is native to Francisella tularensis. AB - The class A beta-lactamase FTU-1 produces resistance to penicillins and ceftazidime but not to any other beta-lactam antibiotics tested. FTU-1 hydrolyzes penicillin antibiotics with catalytic efficiencies of 10(5) to 10(6) M(-1) s(-1) and cephalosporins and carbapenems with catalytic efficiencies of 10(2) to 10(3) M(-1) s(-1), but the monobactam aztreonam and the cephamycin cefoxitin are not substrates for the enzyme. FTU-1 shares 21 to 34% amino acid sequence identity with other class A beta-lactamases and harbors two cysteine residues conserved in all class A carbapenemases. FTU-1 is the first weak class A carbapenemase that is native to Francisella tularensis. PMID- 22083490 TI - Pyranocoumarins isolated from Peucedanum praeruptorum Dunn suppress lipopolysaccharide-induced inflammatory response in murine macrophages through inhibition of NF-kappaB and STAT3 activation. AB - Praeruptorin C, D, and E (PC, PD, and PE) are three pyranocoumarins isolated from the dried root of Peucedanum praeruptorum Dunn of Umbelliferae. In the present study, we investigated the anti-inflammatory effect of these compounds in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Pyranocoumarins significantly inhibited LPS-induced production of nitric oxide, interleukin-6 (IL 6), and tumor necrosis factor-alpha (TNF-alpha). The mRNA and protein expressions of inducible nitric oxide synthase, IL-6, and TNF-alpha were also suppressed by these compounds. Both PD and PE exhibited greater anti-inflammatory activities than PC. Further study showed that pyranocoumarins suppressed the cytoplasmic loss of inhibitor kappaB-alpha protein and inhibited the translocation of NF kappaB from cytoplasm to nucleus. In addition, pyranocoumarins suppressed LPS induced STAT3 tyrosine phosphorylation. Taken together, the results suggest that pyranocoumarins may exert anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages through the inhibition of NF-kappaB and STAT3 activation. PMID- 22083491 TI - Acute oxidative stress affects IL-8 and TNF-alpha expression in IPEC-J2 porcine epithelial cells. AB - Reactive oxygen species are implicated in cell and tissue damage in a number of diseases including acute and chronic inflammation of the gut. Effects of H(2)O(2) exposure on non-carcinogenic porcine epithelial cell line, IPEC-J2 cells cultured on collagen-coated membrane inserts were monitored based on transepithelial electrical resistance (TER) change, extent of necrotic cell damage, gene expression of inflammatory cytokines IL-8 and TNF-alpha. Furthermore, the junction proteins claudin-1 and E-cadherin were also investigated by immunohistochemistry. Peroxide (1mM) increased IL-8 and TNF-alpha gene expression levels significantly allowing 1 h recovery time without affecting the cellular distribution of junction proteins, TER and cell survival rate. In conclusion, the IPEC-J2 cell line on membrane insert was introduced as a fast and reliable investigation tool for oxidative stimuli-triggered intestinal inflammation and in the future as a screening method for antioxidant and probiotic candidates. PMID- 22083493 TI - Absence of caveolin-1 alters heat shock protein expression in spontaneous mammary tumors driven by Her-2/neu expression. AB - In a previous study, we measured caveolin-1 protein levels, both in the normal breast and in breast cancer. The study revealed no association between caveolin-1 expression in the epithelial compartment and clinical disease outcome. However, high levels of caveolin-1 in the stromal tissue surrounding the tumor associated strongly with reduced metastasis and improved survival. Using an animal model, we found that the onset of mammary tumors driven by Her-2/neu expression was accelerated in mice lacking caveolin-1. We have analysed the heat shock protein (Hsp) response in the tumors of mice lacking caveolin-1. In all cases, the mammary tumors were estrogen and progesterone receptor negative, and the levels of Her-2/neu (evaluated by immunohistochemistry) were not different between the caveolin-1 +/+ (n = 8) and the caveolin-1 -/- (n = 7) tumors. However, a significant reduction in the extent of apoptosis was observed in mammary tumors from animals lacking caveolin-1. While Bcl-2, Bax, and survivin levels in the tumors were not different, the amount of HSPA (Hsp70) was almost double in the caveolin-1 -/- tumors. In contrast, HSPB1 (Hsp27/Hsp25) levels were significantly lower in the caveolin-1 -/- tumors. The mammary tumors from caveolin-1 null mice expressed more HSPC4 (gp96 or grp94), but HSPC1 (Hsp90), HSPA5 (grp78), HSPD1 (Hsp60), and CHOP were not altered. No significant changes in these proteins were found in the stroma surrounding these tumors. These results demonstrate that the disruption of the Cav-1 gene can cause alterations of specific Hsps as well as tumor development. PMID- 22083494 TI - Synthesis of geminal bisphosphonates via organocatalyzed enantioselective Michael additions of cyclic ketones and 4-piperidones. AB - A Michael addition reaction of cyclic ketones and piperidones to a vinyl phosphonate is described. The reaction, catalyzed by chiral diamines, produced geminal gamma-oxobisphosphonates in high yields (up to 92%) and very high ees (up to >99%). Disubstituted ketones gave drs of up to 8 : 92. The synthesis and characterization of several new compounds with potential biological activity is described. PMID- 22083495 TI - Revisiting polymer statistical physics to account for the presence of long-range correlated structural disorder in 2D DNA chains. AB - We elaborate on a generalization of the 2D wormlike chain (WLC) model that accounts for the presence of long-range correlations (LRC) in the intrinsic curvature distribution of eukaryotic DNA. This model predicts some decrease of the DNA persistence length resulting from some large-scale intrinsic curvature induced by sequence-dependent persistent random distribution of local bending sites. When assisting exact analytical calculations by numerical DNA simulations, we show that the conjugated contributions of i) the thermal curvature fluctuations characterized by the "dynamic" persistence length l(p)(d) = 2A, where A is the elastic bending modulus, and ii) the intrinsic LRC curvature disorder of amplitude sigma(o) and Hurst exponent H > 1/2, characterized by a "static" persistence length l(p)(H) = A(1/2H)sigma(o)(-1/H) Gamma(1/2H + 1), can be described by a continuum of generalized WLC (GWLC) models parametrized by the LRC exponent H. We use perturbation analysis to investigate the two limiting cases of weak static disorder (w(H) << 1 and weak dynamical fluctuations (1/w (H) << 1), where w(H) = l(p)(d)/l(p)(H) is a dimensionless parameter. From a quantitative point of view, our study demonstrates that even for a small value of the LRC (H approximately equal 0.6-0.8) static disorder amplitude sigma(o) ~ 10( 2), as previously reported for genomic DNA, the decrease of the persistence length from the WLC prediction l(p)(d) can be very significant, up to twofold. The implications of these results on the first steps of compaction of DNA in eukaryotic cells are discussed. PMID- 22083496 TI - Fatty acid composition of Celta pig breed as influenced by sex and location of fat in the carcass. AB - BACKGROUND: The influence of sex and location of fat in the carcass on the fatty acid profile of Celta pigs was studied. Twenty pigs (10 castrated males and 10 females) from the Carballina line were used. RESULTS: The fatty acids composition was predominated by monounsaturated fatty acids (MUFA; approximately 48% of total methyl esters), followed by saturated fatty acids (SFA; approximately 40% of total methyl esters) and, finally, polyunsaturated fatty acids (PUFA; approximately 12% of total methyl esters). The sex and location of fat in the carcass showed significant differences in PUFA and SFA content while both factors were not significantly different with respect to MUFA content. Linoleic, linolenic, eicosatrienoic and arachidonic fatty acids showed the largest difference among the three locations (intramuscular, subcutaneous ventral and subcutaneous dorsal) of the fat in the carcass. CONCLUSION: The fatty acid profile that we observed in the fat of the Celta pigs does not differ greatly from those described by other authors in other autochthonous pig breeds. Principal component analysis offered a good separation of the mean samples according to the sex and location of fat of the pigs. PMID- 22083497 TI - Neutrophil gelatinase-associated lipocalin is instrumental in the pathogenesis of antibody-mediated nephritis in mice. AB - OBJECTIVE: The mechanism by which anti-DNA antibodies mediate lupus nephritis has yet to be conclusively determined. Previously, we found that treatment of mesangial cells with anti-DNA antibodies induced high expression of neutrophil gelatinase-associated lipocalin (NGAL), an iron-binding protein up-regulated in response to kidney injury. We undertook this study to determine whether NGAL is instrumental in the pathogenesis of nephritis, is induced as part of repair, or is irrelevant to damage/repair pathways. METHODS: To investigate the role of NGAL in antibody-mediated nephritis, we induced nephrotoxic nephritis by passive antibody transfer to 129/SyJ and C57BL/6 mice. To determine if NGAL up-regulation is instrumental, we compared the severity of renal damage in NGAL wild-type mice and NGAL-knockout mice following induction of nephrotoxic nephritis. RESULTS: We found that kidney NGAL expression, as well as urine NGAL levels, were significantly increased in mice with nephrotoxic nephritis as compared to control injected mice. Tight correlations were observed between NGAL expression, renal histopathology, and urine NGAL excretion. NGAL-knockout mice had attenuated proteinuria and improved renal histopathology compared to wild-type mice. Similarly, following nephritis induction, NGAL injection significantly exacerbated nephritis and decreased survival. NGAL induced apoptosis via caspase 3 activation and up-regulated inflammatory gene expression in kidney cells in vitro and when injected in vivo. CONCLUSION: We conclude that kidney binding of pathogenic antibodies stimulates local expression of NGAL, which plays a crucial role in the pathogenesis of nephritis via promotion of inflammation and apoptosis. NGAL blockade may be a novel therapeutic approach for the treatment of nephritis mediated by pathogenic antibodies, including anti-glomerular basement membrane disease and lupus nephritis. PMID- 22083498 TI - Demonstration and manifestation of self-determination and illness resistance--a qualitative study of long-term maintenance of physical activity in posttreatment cancer survivors. AB - OBJECTIVE: The aim of this study was to describe posttreatment cancer survivors' lived experience of long-term maintenance of physical activity (PA). METHODS: A qualitative, salutogenetic-oriented study was conducted based on four audiotaped, semistructured focus group interviews. Interviewee selection was carried out through purposeful sampling. Twenty-three cancer survivors (17 women and 6 men; median age 50 years, range 29-70) who were physically inactive prior to their diagnosis but who had been exercising regularly for a minimum of 18 months posttreatment participated in the study. The participants were recruited from The Copenhagen PACT Study that evaluated the effect of a one-year rehabilitation program (supervised exercise [weekly], expert lectures [trimonthly], in-group coaching [bimonthly] and individual coaching [3 * 1 h]). Data were analyzed by use of systematic condensation analysis inspired by Giorgi's descriptive phenomenological methodology (see Sketch of a psychological phenomenological method, in: Giorgi A (ed.), Phenomenology and Psychological Research, Duquesne University Press, Pittsburgh, 1985). RESULTS: The analysis revealed five categories, which were summarized into an overall sentence describing the essence of long-term PA maintenance in cancer survivors: demonstration and manifestation of self-determination and illness resistance. In sum, the participants described regular PA as a prerequisite for feeling and staying well and preserving and pursuing own potentials whereby PA maintenance becomes a goal in itself. CONCLUSIONS: This study indicates that cancer survivors' continued motivation for PA may be dependent on the fulfillment of a personal and conscious experience of being in the process of creating and living a comprehensible and meaningful life. Future theory-based interventions to encourage PA maintenance in cancer survivors could potentially benefit by integration of humanistic and existential psychology in addition to social cognitive theory and theory of planned behavior. PMID- 22083499 TI - Influence of the valgus force during knee flexion in neutral rotation. AB - PURPOSE: The pivot shift test is generally accepted to be a clinically useful tool. In the current study, the authors aimed to determine the minimum amount of valgus force required to elicit a positive pivot shift test utilizing a mechanized pivot shifter device in ACL-deficient knees. The authors proposed that increasing the applied force from a minimum critical value would lead to greater magnitudes of femoro-tibial translation. MATERIALS AND METHODS: Six fresh-frozen pelvis-to-toes specimens were used in this cadaveric study. Tracking and recording of tibiofemoral kinematics during throughout testing was achieved by an image-free surgical navigation system with dedicated ACL software. A load cell was attached to the mechanized pivot shifter through a three-degree-of-freedom arm. Valgus force magnitudes of 0-5 kg were then sequentially applied, and knee flexion in neutral rotation was performed on the ACL-deficient knees. A total of two trials were performed for each force. RESULTS: The greatest difference in lateral and medial compartment translation, during the pivot shift test, utilizing a mechanized pivot shifter in an ACL-deficient knee, was measured between an applied valgus force of 0 and 1 kg. The mean difference between 4 and 5 kg was 0.2 mm (CI = -11.29 to 10.89) for the lateral compartment, and there was no difference in translation for the medial compartment (CI = -17.43 to 17.43). CONCLUSIONS: The principal finding of the current study was that a greater force does not produce a greater magnitude of femoro-tibial translation during knee flexion in neutral rotation, contrary to the initial hypothesis. PMID- 22083500 TI - Behavioral and molecular evidence for a feedback interaction between morphine and HIV-1 viral proteins. AB - Morphine use and addiction is common among HIV infected individuals. There is an abundance of research supporting the effects of morphine and other mu opioid receptor (MOR) ligands, on the function of HIV-1 viral proteins and progression of HIV-1 viral infection to AIDS. On the other hand, there is much less research that investigates the possible effects of the persistent presence of HIV-1 viral proteins on the expression of the MOR and the analgesic and rewarding effects of MOR ligands such as morphine. While researchers have made a great deal of progress in the past several years, the overall investigation of the interaction between opiates such as morphine and HIV-1 viral proteins is largely unilateral. It has become widely accepted that drugs of abuse interact with HIV-1 viral proteins, but the mechanisms by which this takes place are only recently being discovered. Molecular and behavioral research suggests a feedback interaction between morphine and HIV-1 viral proteins. This interaction is mediated largely by the MOR as well as interplay between MOR ligands and cytokines, chemokines and their receptors. Some of the mechanisms underlying the feedback interaction between morphine and HIV-1 viral proteins has been demonstrated using cell culture and the recently engineered HIV-1 transgenic (HIV-1Tg) rat models. PMID- 22083501 TI - Patterns and predictors of self-medication amongst antenatal clients in Ibadan, Nigeria. AB - BACKGROUND: Self-medication is widely practiced in the study area, as many drugs are available over-the-counter, in addition to the use of local herbal preparations. Also, apprehension about the dangers of drug use in pregnancy appears to affect the compliance of prescribed medication. This study assess the drug use profile of an antenatal population. MATERIALS AND METHODS: This was a questionnaire-based descriptive study of 410 antenatal clients attending primary, secondary and tertiary centers in Ibadan, Nigeria. The variables analysed were demographic data of respondents and level of health care received. Outcome measures were use of prescribed drugs, self-medication or herbal preparations. Chi-tests and logistic regression were used for statistical analysis. RESULTS: All patients on prescribed medication for medical conditions claimed to be compliant with their drugs. Exactly 19.2% admitted to self-medication, mostly hematinics and pain-relieving pills (acetaminophen). No one admitted to alcohol or tobacco use, but 46.3%, especially attendees of the rural center (OR 5.79; 95% CI 2.56-13.10), ingested herbal concoctions while pregnant. Married women (OR 0.2; 95% CI 0.05-0.75) or those whose spouses had higher education (OR 0.43; 95% CI 0.21-0.89) were less likely to practice self-medication, while hypertensive women were more likely to practice it (OR 22.54; 95% CI 3.81-133.49). CONCLUSIONS: Social support has a role in safe drug use practices. This should be used to advantage by encouraging partners' attendance at antenatal sessions. Patients need counseling on the dangers of procuring their usual prescription drugs without consultation. Use of herbal concoctions needs to be explored in the community. PMID- 22083502 TI - An unusual cause of acute renal failure in a patient with surgical hypoparathyroidism: nephrocalcinosis. PMID- 22083503 TI - Papillary thyroid microcarcinoma in struma ovarii. PMID- 22083504 TI - Quantification of image quality using information theory. AB - Aims of present study were to examine usefulness of information theory in visual assessment of image quality. We applied first order approximation of the Shannon's information theory to compute information losses (IL). Images of a contrast-detail mammography (CDMAM) phantom were acquired with computed radiographies for various radiation doses. Information content was defined as the entropy Sigmap( i )log(1/p ( i )), in which detection probabilities p ( i ) were calculated from distribution of detection rate of the CDMAM. IL was defined as the difference between information content and information obtained. IL decreased with increases in the disk diameters (P < 0.0001, ANOVA) and in the radiation doses (P < 0.002, F-test). Sums of IL, which we call total information losses (TIL), were closely correlated with the image quality figures (r = 0.985). TIL was dependent on the distribution of image reading ability of each examinee, even when average reading ratio was the same in the group. TIL was shown to be sensitive to the observers' distribution of image readings and was expected to improve the evaluation of image quality. PMID- 22083506 TI - Commentary Re: Botox Article by Berger & Knoll IPH 19(5):243-244 on "The efficacy of botulinum toxin type A in managing chronic musculoskeletal pain: a systematic review and meta analysis". PMID- 22083507 TI - A parametric model fitting time to first event for overdispersed data: application to time to relapse in multiple sclerosis. AB - In this article, we propose a parametric model for the distribution of time to first event when events are overdispersed and can be properly fitted by a Negative Binomial distribution. This is a very common situation in medical statistics, when the occurrence of events is summarized as a count for each patient and the simple Poisson model is not adequate to account for overdispersion of data. In this situation, studying the time of occurrence of the first event can be of interest. From the Negative Binomial distribution of counts, we derive a new parametric model for time to first event and apply it to fit the distribution of time to first relapse in multiple sclerosis (MS). We develop the regression model with methods for covariate estimation. We show that, as the Negative Binomial model properly fits relapse counts data, this new model matches quite perfectly the distribution of time to first relapse, as tested in two large datasets of MS patients. Finally we compare its performance, when fitting time to first relapse in MS, with other models widely used in survival analysis (the semiparametric Cox model and the parametric exponential, Weibull, log-logistic and log-normal models). PMID- 22083509 TI - Beneficial effect of myricetin on renal functions in streptozotocin-induced diabetes. AB - Myricetin is a naturally occurring flavonoid that is known to decrease plasma glucose levels in diabetes; however, its influence on renal functions has not yet been determined. This study investigated the effect of myricetin on structural and functional changes occurring in diabetic nephropathy. Male Albino Wistar rats were divided into three groups: normoglycemic, diabetic and myricetin-treated diabetic. Diabetes was induced by intraperitoneal (ip) injection of streptozotocin (50 mg/kg), and rats having fasting blood glucose (FBG) levels greater than 200 mg/dl were included in the study. Treatment of myricetin (6 mg/day ip) was initiated 16 weeks after diabetes was confirmed. Light microscopy was performed on hematoxylin-eosin- and Masson's trichrome-stained sections to evaluate the effect of myricetin on structural changes in the kidney, while creatinine clearance, blood urea nitrogen (BUN), kidney weight, urine volume and protein were measured to assess kidney functions. Activities of glutathione peroxidase (GPx) and xanthine oxidase (XO) were also measured in renal tissues obtained from all experimental groups. Myricetin treatment significantly decreased glomerulosclerosis and reduced BUN, urinary volume and protein excretion, which was profoundly increased in diabetic rats. Decreased creatinine clearance measured in diabetic rats was significantly increased following myricetin treatment. Myricetin also restored altered renal activities of GPx and XO, which were decreased and increased in diabetic rats, respectively. In conclusion, myricetin improved altered renal functions and restored renal activities of GPx and XO in diabetic rats. Obtained data suggest that myricetin could be of therapeutic potential in diabetic nephropathy. PMID- 22083510 TI - Oct4 links multiple epigenetic pathways to the pluripotency network. AB - Oct4 is a well-known transcription factor that plays fundamental roles in stem cell self-renewal, pluripotency, and somatic cell reprogramming. However, limited information is available on Oct4-associated protein complexes and their intrinsic protein-protein interactions that dictate Oct4's critical regulatory activities. Here we employed an improved affinity purification approach combined with mass spectrometry to purify Oct4 protein complexes in mouse embryonic stem cells (mESCs), and discovered many novel Oct4 partners important for self-renewal and pluripotency of mESCs. Notably, we found that Oct4 is associated with multiple chromatin-modifying complexes with documented as well as newly proved functional significance in stem cell maintenance and somatic cell reprogramming. Our study establishes a solid biochemical basis for genetic and epigenetic regulation of stem cell pluripotency and provides a framework for exploring alternative factor based reprogramming strategies. PMID- 22083511 TI - Live imaging of newly formed lymphatic vessels in the cornea. PMID- 22083512 TI - Late effects on haemostasis after haematopoietic stem cell transplantation. AB - Allogeneic and autologous hematopoietic stem cell transplantations are important therapeutic options for patients with hematologic disorders. Hemostatic complications are frequent after hematopoietic stem cell transplantation with a considerable morbidity and mortality. The incidence of bleedings and thrombosis is highest in the first few weeks after transplantation, but may also occur later. However, beyond the first year of transplantation only limited data are available. In long-term survivors the risk for premature atherosclerosis increases over time after allogeneic hematopoietic stem cell transplantation and it is higher than in the age-adjusted general population and in recipients of autologous transplantation. PMID- 22083513 TI - A mathematical model of cell cycle progression applied to the MCF-7 breast cancer cell line. AB - In this paper, we present a model of cell cycle progression and apply it to cells of the MCF-7 breast cancer cell line. We consider cells existing in the three typical cell cycle phases determined using flow cytometry: the G1, S, and G2/M phases. We further break each phase up into model phases in order to capture certain features such as cells remaining in phases for a minimum amount of time. The model is also able to capture the environmentally responsive part of the G1 phase, allowing for quantification of the number of environmentally responsive cells at each point in time. The model parameters are carefully chosen using data from various sources in the biological literature. The model is then validated against a variety of experiments, and the excellent fit with experimental results allows for insight into the mechanisms that influence observed biological phenomena. In particular, the model is used to question the common assumption that a 'slow cycling population' is necessary to explain some results. Finally, an extension is proposed, where cell death is included in order to accurately model the effects of tamoxifen, a common first line anticancer drug in breast cancer patients. We conclude that the model has strong potential to be used as an aid in future experiments to gain further insight into cell cycle progression and cell death. PMID- 22083514 TI - Identification of patients with indolent B cell lymphoma sensitive to rituximab monotherapy. AB - The potential predictive value of tumor bulk, genetic, and immunological variants in patients with low-grade non-Hodgkin's lymphoma to respond to treatment with rituximab (RTX) monotherapy was evaluated. Thus, the value of assessing the effect of 18-fluoro-desoxy-D-glucose (FDG) uptake on PET scan, polymorphisms in Fc gamma receptor (FcgammaR) IIIa-158, FcgammaRIIa-131, and C1qA-276 genes in predicting the response to treatment were evaluated in 50 low-grade non-Hodgkin's lymphoma patients. The influence of RTX pharmacokinetics, plasma levels of the B cell-activating factor (BAFF), and human antichimeric antibodies was also investigated. The therapeutic response was evaluated 10 weeks after treatment using revised Cheson's criteria. Lower maximal standardized uptake values (SUV(max)) at baseline were predictive of complete response. FcgammaRIIIa-158 polymorphism was also associated with complete response to RTX confirming previous findings, whereas polymorphisms in the FcgammaRIIa-131 and C1qA-276 genes were not. Lower blood levels of RTX were observed in males, but the effectiveness of RTX in males and females was the same. BAFF was not detectable in plasma before or after treatment, and no patients developed human antichimeric antibodies. Low-grade non-Hodgkin's lymphoma patients with a low SUV(max) at baseline and an FcgammaRIIIa-158 V/V genotype generally had a complete response to RTX. PMID- 22083515 TI - Center-by-center results of a multicenter prospective trial to determine the inter-observer correlation of the simplified POP-Q in describing pelvic organ prolapse. AB - INTRODUCTION AND HYPOTHESIS: This study was conducted to determine the differences in the inter-observer agreement of the simplified Pelvic Organ Prolapse Quantification (POP-Q) system from center to center in a large international multicenter study. METHODS: This is a secondary analysis of the results of a large prospective single blind multicenter trial studying the inter observer agreement of a simplified POP-Q exam. Twelve centers from four continents with a total of 511 subjects were included in this study. The number of subjects recruited per center ranged from 20 to 81. Each patient was independently examined by two investigators, with examination order randomly assigned and investigators blinded to each other's result. The weighted kappa statistic was used to evaluate the inter-observer agreement. RESULTS: Good and significant associations were observed on the anterior, posterior, and apical segments. Six out of 11 sites did not provide adequate number of subjects with prior hysterectomy for weighted kappa statistics or achieve significance regarding vaginal cuff measurement. CONCLUSIONS: The simplified POP-Q demonstrated good inter-examiner agreement across multiple centers. PMID- 22083518 TI - Middle pancreatectomy. AB - Middle pancreatectomy is parenchyma- and adjacent organ-sparing pancreatectomy indicated for small tumors located in the body, but deeply located in the gland, and therefore hard to enucleate. Others lesions including pancreatic trauma or arteriovenous malformation are also candidate targets. Invasive ductal carcinoma, even when the tumor is small enough, is not eligible because the most of these tumors show extrapancreatic invasion. After exposure of neck to body of the pancreas, middle pancreatectomy was performed by proximal and distal transection, reconstruction after Roux-Y pancreaticojejunostomy, which is the most common. This procedure is low-invasive and allow the preservation of exocrine and endocrine pancreatic function without loss of duodenal passage, however, it also has a high morbidity associated with pancreatic fistula. This article provides indications and surgical techniques with special focus on the procedure of middle pancreatectomy. PMID- 22083517 TI - Pancreaticoduodenectomy for invasive pancreatic cancer (with video). AB - Pancreaticoduodenectomy (PD) is the only treatment option that potentially provides a cure for pancreatic head cancer. Various arrangements and modifications have been proposed to achieve pathological margin negative (R0) resection safely. In this article, we introduce a standard procedure for PD, including pancreaticogastrostomy with invagination and mattress sutures (video clip provided), for invasive ductal carcinoma of the pancreatic head, with a description of the need-to-know pitfalls for Board-certified HBP surgeons in Japan. The important points in performing PD for pancreatic cancer are: (1) While dissecting connective tissue and nerve plexus as well as lymph nodes, maintain a dissection plane to expose the surfaces of vessels or other organs to be preserved to achieve R0 resection: i.e., while dissecting the anterior surface of the inferior vena cava and the right side of the superior mesenteric artery, these vessels should be completely exposed with the connective tissue and nerve plexuses being attached to the resection side. (2) There should be early interruption of the afferent blood supply via the inferior pancreaticoduodenal artery to reduce blood loss by avoiding congestion of the pancreatic head and to increase the operative safety (video clip provided). (3) Eligibility for PD should be carefully evaluated because there are many "resectable" but not many "curable" cases. In addition, the clinical significance of various modifications of the surgical techniques used for PD are also discussed. PMID- 22083516 TI - Loss of matrilin 1 does not exacerbate the skeletal phenotype in a mouse model of multiple epiphyseal dysplasia caused by a Matn3 V194D mutation. AB - OBJECTIVE: Mutations in matrilin 3 can result in multiple epiphyseal dysplasia (MED), a disease characterized by delayed and irregular bone growth and early onset osteoarthritis. Although intracellular retention of the majority of mutant matrilin 3 was previously observed in a murine model of MED caused by a Matn3 V194D mutation, some mutant protein was secreted into the extracellular matrix. Thus, it was proposed that secretion of mutant matrilin 3 may be dependent on the formation of hetero-oligomers with matrilin 1. The aim of this study was to investigate the hypothesis that deletion of matrilin 1 would abolish the formation of matrilin 1/matrilin 3 hetero-oligomers, eliminate the secretion of mutant matrilin 3, and influence disease severity. METHODS: Mice with a Matn3 V194D mutation were crossed with Matn1-null mice, generating mice that were homozygous for V194D and null for matrilin 1. This novel mouse was used for in depth phenotyping, while cartilage and chondrocytes were studied both histochemically and biochemically. RESULTS: Endochondral ossification was not disrupted any further in mice with a double V194D mutation compared with mice with a single mutation. A similar proportion of mutant matrilin 3 was present in the extracellular matrix, and the amount of retained mutant matrilin 3 was not noticeably increased. Retained mutant matrilin 3 formed disulfide-bonded aggregates and caused the co-retention of matrilin 1. CONCLUSION: We showed that secretion of matrilin 3 V194D mutant protein is not dependent on hetero oligomerization with matrilin 1, and that the total ablation of matrilin 1 expression has no impact on disease severity in mice with MED. Mutant matrilin 3 oligomers form non-native disulfide-bonded aggregates through the misfolded A domain. PMID- 22083519 TI - Development of more labile low electron count Co(I) sources: mild, catalytic functionalization of activated alkanes using a [(Cp*Co)2-MU-(eta4:eta4-arene)] complex. AB - Catalytic transfer dehydrogenation of silyl protected amines, requiring sp(3) C-H bond activation, is mediated by a bridging arene complex of the type [(Cp*Co)(2) MU-(eta(4):eta(4)-arene)] under mild conditions. Mechanistic and qualitative rate studies establish the compound as a more reactive Co(I) source when compared to other known Cp*Co(I) complexes. PMID- 22083520 TI - Characterization of a multilayer film activated with Lactobacillus curvatus CRL705 bacteriocins. AB - BACKGROUND: Bacteriocins produced by lactic acid bacteria offer enormous promise for food safety preservation. In this study an active multilayer film obtained by the incorporation of lactocin 705 and lactocin AL705, two bacteriocins produced by Lactobacillus curvatus CRL705 with antimicrobial activity against Lactobacillus plantarum CRL691 and Listeria innocua 7, respectively, was characterized for its potential application in active packaging technology. Film activity performance at different storage conditions, bacteriocins transfer into water and sunflower oil, and film surface properties were evaluated. RESULTS: Film activity against L. innocua 7 was maintained during 2, 4 and 6 weeks at 30, 10 and 5 degrees C respectively. At 30 and 10 degrees C, activity loss against L. plantarum CRL691 was observed on the second week of storage and after the fourth week at 5 degrees C. Results showed no significant difference for active multilayer film contact angle and seal properties compared to the control (without bacteriocins). A decrease in lactocin 705 inhibitory activity after sunflower oil contact was observed, while lactocin AL705 remained unaffected. After water contact, film activity was retained for both bacteriocins. CONCLUSIONS: As demonstrated by antimicrobial activity and physico-mechanical properties retention, lactocin 705 and AL705 active multilayer film present potential for application in active packaging technology. PMID- 22083521 TI - A multiscale description of molecular adsorption on gold nanoparticles by nonlinear optical spectroscopy. AB - Nonlinear optical Sum and Difference-Frequency spectroscopies are used to probe and model the surface of thiophenol-functionalised gold nanoparticles grafted on a Si(100) substrate through two different silanization procedures. By scanning the [980-1100 cm(-1)] infrared spectral range with the CLIO Free Electron Laser, ring deformation vibrations of adsorbed thiophenol are investigated. Quantitative data analysis addresses three levels of organization: microscopic, nanoscopic and molecular. Grafting with p-aminophenyl-trimethoxysilane shows an increase of around 40% in surface density of nanoparticles (N(s)) as compared to 3 aminopropyl-triethoxysilane. The relative amplitudes of the resonant and nonresonant contributions to the SFG and DFG spectra are discussed in terms of N(s), Fresnel reflectivity factors and local amplification of the nonlinear signals by coupling to the surface plasmon of the particles. They are shown to quantitatively scale with N(s), as measured by atomic force microscopy. Vibration mode assignment is performed through a critical analysis of literature data on IR and Raman spectroscopies coupled to DFT calculations, for which a methodology specific to molecules adsorbed on gold atoms is discussed. PMID- 22083522 TI - The benefit of myomectomy in women aged 40 years and above: Experience in an urban teaching hospital in Nigeria. AB - BACKGROUND: Abdominal myomectomy remains the mainstay of surgical management of uterine fibroids in our environment. However, its benefit in women aged 40 years and above remains debatable. MATERIALS AND METHODS: An 11-year prospective study was conducted involving 98 women, aged 40 years and above, who had abdominal myomectomy for the treatment of uterine fibroid at the University of Maiduguri Teaching Hospital, Maiduguri. They were followed up regularly for 1-6 years to detect conception, resolution of symptoms and obstetrics performance. Data were analyzed using SPSS version 13. RESULTS: The mean age of the patients was 42.6+/ 2.9 years and 77 (78.6%) of them were nulliparous. Lower abdominal swelling was the commonest clinical presentation and the mean uterine size was 18.6+/-8.5 weeks. Infertility with uterine fibroids was the indication for myomectomy in majority of the cases [48 (48.9%)], while pregnancy complications accounted for 11.2% (11) of the cases Fertility restoration was 10.4% among the infertile patients. There was complete resolution of symptoms in 35.9% of those who required symptomatic relief, and term pregnancies were recorded in 72.7% of patients with pregnancy complications. CONCLUSION: Myomectomy is the recommended treatment of uterine fibroids in women aged 40 years and above with infertility and who wish to become pregnant. If there is no need for further fertility preservation, hysterectomy should be offered. PMID- 22083523 TI - Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients. AB - PURPOSE: To evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in patients with locally advanced basal-like breast cancers (BLBCs). PATIENTS AND METHODS: Thirty two BLBC patients receiving NACT with an anthracycline-based regimen plus taxane were included in this study. The immunoreactivities of MGMT, MLH1, MSH2 and BRCA1 before and after NACT were evaluated. RESULTS: A pCR was obtained in 10 of 32 cases (31%). Cancer-related (P = 0.013) and disease-free (P = 0.023) survival rates were significantly higher in the pCR group than in the non-pCR group. In biopsy samples before NACT, attenuated expression of MGMT, MLH1, MSH2 and BRCA1 was observed in 12/32 (38%), 0/32 (0%), 5/32 (16%) and 28/32 (88%) cases, respectively. On evaluation of pCR, patients' characteristics (patients' age, menopausal status, or clinical and pathological stages) and immunohistochemical patterns, attenuated expression of MGMT was only found to be significantly predictive of a pCR (P = 0.018). Paired biopsy sample before NACT and a surgical tumor material after NACT were available for 19 cases of non-pCR. In these cases, decrease in expression during NACT were more frequently observed for MGMT as compared to MLH1, MSH2 or BRCA1 (P = 0.021). CONCLUSIONS: MGMT status is a predictive factor for pCR with neoadjuvant anthracycline-based plus taxane combination chemotherapy, which may be helpful in the selection of appropriate NACT for Japanese patients with BLBC. PMID- 22083524 TI - Sea cucumber aquaculture in the Western Indian ocean: challenges for sustainable livelihood and stock improvement. AB - The decline in sea cucumber fisheries that serve the Asian dried seafood market has prompted an increase in global sea cucumber aquaculture. The tropical sandfish (Holothuria scabra) has, in this context, been reared and produced with mixed success. In the Western Indian Ocean, villagers often participate in the export fishery for sea cucumbers as a source of income. However, with a growing concern of depleted stocks introduction of hatcheries to farm sandfish as a community livelihood and to replenish wild stocks is being promoted. This review identifies and discusses a number of aspects that constitute constraints or implications with regard to development of sandfish farming in the region. The conclusion is that for sandfish farming to live up to its expectations the possible impacts need to be further studied, and that improved evaluation of ongoing projects is required. In the interim, a precautionary approach toward new enterprise activities is suggested. PMID- 22083525 TI - Lysine acetylation in obesity, diabetes and metabolic disease. AB - Histone acetyltransferases (HATs) and histone deacetylases (HDACs) mediate acetylation and deacetylation of histone proteins and transcription factors. There is abundant evidence that these enzymes regulate the acetylation state of many cytoplasmic proteins, including lysine residues in important metabolic enzymes. Lysine acetylation regulates major cellular functions as a common post transcriptional modification of proteins, conserved from prokaryotes to humans. In this article, we refer to HATs and HDACs broadly as lysine acetyltransferases (KATs) and deacetylases (KDACs). Lysine acetylation is vitally important in both immunological and metabolic pathways and may regulate the balance between energy storage and expenditure. Obesity, type II diabetes and cardiovascular disease (metabolic syndrome) are widely recognised as features of a chronic low-grade inflammatory state, involving significant alterations in primary immunometabolism. Identifying effective therapeutic and preventive options to treat this multi-factorial syndrome has proven to be very challenging, with an emerging focus on developing anti-inflammatory agents that can combat adiposity and metabolic disease. Here, we summarise current evidence and understanding of innate immune and metabolic pathways relevant to adiposity and metabolic disease regulated by lysine acetylation. Developing this understanding in greater detail may facilitate strategic development of novel and enzyme-specific lysine deacetylase modulators that regulate both metabolic and immune systems. PMID- 22083526 TI - Arginase-dependent suppression by CpG-ODN plus IFA-induced splenic myeloid CD11b(+)Gr1(+) cells. AB - The ability of synthetic oligodeoxynucleotides containing unmethylated cytosine guanine motifs (CpG-ODN) to induce both stimulatory and counter-regulatory responses offers novel opportunities for using these molecules as immunomodulatory agents in different therapeutic strategies. Here, we investigated the potential of CpG-ODN to activate the arginase (ARG) enzyme in vivo and focused on the consequences of this activation in T-cell proliferation. Challenging mice subcutaneously with CpG-ODN emulsified in incomplete Freund's adjuvant (IFA) induced ARG and reduced T-cell proliferation associated with CD3zeta chain downregulation. Interestingly, impaired T-cell expansion correlated with elevated levels of CD11b(+)Gr1(+) myeloid cells localized near T-cell areas in the spleen. In addition, purified CD11b(+) cells obtained from the spleen of CpG-ODN+IFA-treated mice exhibited increased ARG activity and ARG I expression along with an augmented [(3)H]-L-arginine uptake. CD11b(+) myeloid cells significantly suppressed T-cell proliferation and CD3zeta chain expression induced by a polyclonal stimulus. Furthermore, these effects could be recovered by the addition of excess L-arginine or by treatment of CD11b(+) cells with a specific ARG inhibitor. This study provides a novel evidence that CpG-ODN+IFA are able to induce splenic CD11b(+) cells with ARG activity, with this population being responsible for the impaired T-cell proliferation observed after the treatment with CpG-ODN+IFA. These results underscore a key role of CpG-ODN on ARG activity in vivo and add support to the growing body of evidence in favor of a counter-regulatory role for CpG-ODN in an immune response. PMID- 22083527 TI - HDACi: molecular mechanisms and therapeutic implications in the innate immune system. AB - Histone deacetylase inhibitors (HDACi) are an emerging class of novel anti-cancer drugs that cause growth arrest, differentiation and apoptosis of tumor cells. In addition, many advances have been made in understanding the immunoregulation of Toll-like receptors, NOD-like receptors and interferons that have recently generated new momentum for the study of HDACi in immunity as a whole, and in the regulation of these innate signaling pathways specifically. HDACi have shown promise as new anti-inflammatory and immunosuppressant agents. They have also demonstrated great potency and relative selectivity in various human/animal models of inflammatory diseases. This review focuses on recent progress and the current state of HDACi knowledge, as well as the molecular mechanisms and therapeutic potential of HDACi for the treatment of inflammatory diseases and cancers. PMID- 22083528 TI - HDAC inhibitors in HIV. AB - Combination antiretroviral therapy (cART) has led to a very substantial reduction in morbidity and mortality in HIV-infected patients; however, cART alone is unable to cure HIV and therapy is lifelong. Therefore, a new strategy to cure HIV is urgently needed. There is now a concerted effort from scientists, clinicians and funding agencies to identify ways to achieve either a functional cure (long term control of HIV in the absence of cART) or a sterilizing cure (elimination of all HIV-infected cells). Multiple strategies aiming at achieving a cure for HIV are currently being investigated, including both pharmacotherapy and gene therapy. In this review, we will review the rationale as well as in vitro and clinical trial data that support the role of histone deacetylase inhibitors as one approach to cure HIV. PMID- 22083529 TI - Sensitivity of human dental pulp cells to eighteen chemical agents used for endodontic treatments in dentistry. AB - To determine the adverse effects against human dental pulp tissue, the sensitivity of human dental pulp cells (D824 cells) to 18 chemical agents used for endodontic treatments in dentistry was examined. The cytotoxicity, as determined by a decrease in colony-forming ability of cells treated with the chemical agents, increased as the concentration increased. As a quantitative measure of the cytotoxic effect, LC(50), the concentration which induces a 50% lethality, was extrapolated from the concentration-response curves. The rank of the chemical agents according to their cytotoxic effect (LC(50)) was sodium arsenite > formaldehyde > hydrogen peroxide > zinc oxide > thymol ~ iodoform ~ eugenol > guaiacol > ethylenediaminetetraacetic acid ~ iodine > procaine > lidocaine ~ chloramphenicol ~ m-cresol > calcium hydroxide ~ sodium hypochlorite ~ phenol ~ p-phenolsulfonic acid. To compare the cytotoxicity and the levels of apoptosis and mRNA expression of five genes related to the function of dental pulp tissue, D824 cells treated with the LC(50) concentrations of chemical agents were assayed by the TUNEL method and quantitative reverse transcription polymerase chain reaction analysis, respectively. The inducibility of apoptotic cells and the level of mRNA expression of the genes varied with the chemical agents, indicating that both effects occurred independent of the rank of cytotoxic effect of the chemical agents. The results not only provide information concerning cytotoxicity of various chemical agents to human dental pulp cells, but also show an insight into the diversity of the pharmacodynamic action of the chemical agents. PMID- 22083530 TI - Conversion reaction mimicking a high spinal anesthesia. PMID- 22083531 TI - Effect of surgeon volume on outcome following pancreaticoduodenectomy in a high volume hospital. AB - BACKGROUND: Despite the close relationship between hospital volume and mortality after pancreaticoduodenectomy (PD), the role of surgeon volume still remains an open issue. Retrospective multi-institutional reviews considered only in-hospital mortality, whereas no data about major complications are available so far. The aim of this study is to assess the independent impact of surgeon volume on outcome after PD in a single high-volume institution. METHODS: Demographics and clinical and surgical variables were prospectively collected on 610 patients who underwent PD from August 2001 to August 2009. The cutoff value to categorize high and low-volume surgeons (HVS and LVS, respectively) was 12 PD/year. The primary endpoint was operative mortality (death within 30-day post-discharge). Secondary endpoints were morbidity, pancreatic fistula (PF), and length of hospital stay (LOS). RESULTS: In the whole series, mortality was 4.1%, overall morbidity was 61.3%, and PF rate was 27.5%. Two HVS performed 358 PD (58.6%), while six LVS performed 252 PD (41.4%). Mortality was 3.9% for HVS and 4.3% for LVS (p=0.84). The major complication rate was similar for HVS and LVS (14.5% vs. 16.2%). The PF rate was higher for LVS (32.4% vs. 24.1%, p=0.03). The mean LOS was 15.5 days for HVS vs. 16.9 days for LVS (p=0.11). At multivariate analysis, risk factors for PF occurrence were LVS, soft pancreatic stump, small duct diameter, and longer operative time. CONCLUSION: Low-volume surgeons had a higher PF rate. However, this did not increase mortality and major morbidity rates probably because of the protective effect of high-volume hospital in improving patient rescue from life threatening complications. PMID- 22083532 TI - LFA-1 expression in a series of colorectal adenocarcinomas. AB - INTRODUCTION: LFA-1 is an adhesion molecule which belongs to the beta2-integrin family. Overexpression of LFA-1 in hepatic natural killer cells has been associated with increased apoptosis of neoplastic cells in colorectal cancer (CRC); moreover, studies in CRC have linked LFA-1 overexpression in neoplastic cells with vascular intrusion through adhesion to endothelial cells, thus implying a possible role in creation of metastases. AIMS AND METHODS: We studied the expression of LFA-1 in a series of 82 patients with CRC. A standard three step immunohistochemical analysis was performed on formalin-fixed, paraffin embedded tissue sections. An IgG2a anti-CD11a monoclonal antibody was used. Cases were characterized according to clinicopathological variables including sex, age, tumor localization, size, grade, Dukes stage, wall invasion, and presence of metastatic lymph nodes (mLNs) or distal metastases. RESULTS: LFA-1 was expressed at the primary tumor site in 51 cases and 6/33 cases with metastatic lymphnodes. In Dukes D cases (n = 4), only one case was LFA-1(+). LFA-1 expression at the primary tumor site was associated with the absence of metastatic disease and with Dukes B stage. However, in those cases with LFA-1 expression in cancer cells in mLNs, this was associated with its expression at the primary tumor site. CONCLUSION: The positive association of LFA-1 expression in mLNs when the primary tumor site is also LFA-1(+) could imply an adaptation advantage of this specific cellular clone to its micro-environment, predisposing it to creation of mLNs, pointing to a role for LFA-1 in creation of mLNs in CRC. PMID- 22083533 TI - Concomitant Nonfunctional Pancreatic Neuroendocrine Tumor and Gastric GIST in a Patient Without Neurofibromatosis Type 1. PMID- 22083534 TI - Sustainable food and local development. PMID- 22083535 TI - A centrifuge simulated push-pull manoeuvre with subsequent reduced +Gz tolerance. AB - The push-pull effect (PPE) has been recognized as a deleterious contributor to fatal flight accidents. The purpose of the study was to establish a push-pull manoeuvre (PPM) simulation with a tri-axes centrifuge, studying the effect of this PPM on the +Gz tolerance, and to make this simulation suitable for pilot centrifuge training. The PPM was realized through pre-programmed acceleration profiles consisting of -1 Gz for 5 s followed by a +Gz plateau for 10 s. Relaxed +Gz tolerance recordings were obtained from 20 healthy male fighter aircraft pilots and 6 healthy male volunteers through exposure to pre-programmed profiles with and without previous -1 Gz exposure. A statistically significant decrease in +Gz tolerance was seen in all subjects after -1 Gz for 5 s exposure, 0.87 +/- 0.13 G in the volunteer group and 0.95 +/- 0.25 G in the pilot group. The ear opacity pulse as a +Gz tolerance endpoint criterion was sometimes found to be unreliable during the PPM experiments. The simulated PPM in this study elicited a PPE, which was obvious from the significant reduction in +Gz tolerance. The PPM profile appears useful to be included in centrifuge training. PMID- 22083536 TI - Comparison of the acute impact of maximal arm and leg aerobic exercise on arterial stiffness. AB - Acute aerobic exercise decreases arterial stiffness based on the intensity of the exercise and the arterial segment studied. Arm exercise may differentially affect arterial stiffness compared to leg exercise but this has not been studied. We hypothesized that maximal aerobic exercise would reduce local peripheral pulse wave velocity i.e. femoral-dorsalis pedis (LPWV) following leg exercise and carotid-radial (APWV) following arm exercise without any crossover effect. The main purpose of the study is to compare the effects of maximal arm versus leg aerobic exercise on peripheral and central arterial stiffness. Fifteen healthy participants (9 males and 6 females, 25 +/- 5 years) performed maximal arm ergometer and leg-ergometer exercise in a randomized, crossover design. Peripheral and central pulse wave velocities (PWV) were obtained using applanation tonometry before and 10 min after each maximal exercise bout. 2 * 2 repeated measures analysis of variance was used to detect differences between conditions. There was a significant interaction in the APWV between the two exercise modes. However, there was no condition or interaction effect on LPWV following maximal arm versus leg exercise. There was no significant difference in central PWV between conditions or with time. There was no change in MAP (75 +/- 6 77 +/- 3) after maximal arm exercise as compared to the maximal leg exercise (73 +/- 6-80 +/- 2). Arm exercise produced a more generalized effect on arterial stiffness than leg exercise. The prescription of upper limb exercise may be considered for purposes of eliciting post-exercise systemic changes in arterial stiffness. PMID- 22083537 TI - The art of medicine: recognising influenza and pneumonia. PMID- 22083538 TI - Knowledge of asthma management by general practitioners in Karachi, Pakistan: comparison with international guidelines. AB - BACKGROUND: Suboptimal management of asthma by general practitioners (GPs) can lead to poor health outcomes AIMS: To assess the management of common asthma presentations by GPs using the Global Initiative for Asthma (GINA) guidelines as a comparative tool. METHODS: A cross-sectional survey was conducted in Karachi, Pakistan. Of 250 GPs approached, 192 completed a self-administered questionnaire regarding pathology, key history points, risk factors, diagnosis, and management of asthma. RESULTS: Overall, 28.6% of GPs had adequate knowledge of the core concepts of asthma, while only 10.4% had adequate practice in asthma management. About 78% of GPs had inadequate knowledge of pathology, about 90% had inadequate knowledge of medications to be used, and 63% had inadequate knowledge regarding diet restrictions. Knowledge regarding symptoms not usually associated with asthma was adequate, as was knowledge regarding non-pharmacological management (79% each). Practices regarding asthma diagnosis were good (99.0%). However, practices regarding acute exacerbations and patients who wish to exercise were inadequate in 85.9% and 82.8% of GPs, respectively. CONCLUSIONS: The majority of GPs had poor knowledge and practice of asthma. We recommend initiation of programmes to improve their knowledge and practices. PMID- 22083540 TI - Relationship between cardiovascular disease knowledge and race/ethnicity, education, and weight status. AB - BACKGROUND: Inadequate cardiovascular disease (CVD) knowledge has been cited to account for the imperfect decline in CVD among women over the last 2 decades. HYPOTHESIS: Due to concerns that at-risk women might not know the leading cause of death or symptoms of a heart attack, our goal was to assess the relationship between CVD knowledge race/ethnicity, education, and body mass index (BMI). METHODS: Using a structured questionnaire, CVD knowledge, socio-demographics, risk factors, and BMI were evaluated in 681 women. RESULTS: Participants included Hispanic, 42.1% (n = 287); non-Hispanic white (NHW), 40.2% (n = 274); non Hispanic black (NHB), 7.3% (n = 50); and Asian/Pacific Islander (A/PI), 8.7% (n = 59). Average BMI was 26.3 +/- 6.1 kg/m(2) . Hypertension was more frequent among overweight (45%) and obese (62%) than normal weight (24%) (P < 0.0001), elevated total cholesterol was more frequent among overweight (41%) and obese (44%) than normal weight (30%) (P < 0.05 and P < 0.01, respectively), and diabetes was more frequent among obese (25%) than normal weight (5%) (P < 0.0001). Knowledge of the leading cause of death and symptoms of a heart attack varied by race/ethnicity and education (P < 0.001) but not BMI. Concerning the leading cause of death among women in the United States, 87.6% (240/274) NHW answered correctly compared to 64% (32/50) NHB (P < 0.05), 28.3% (80/283) Hispanic (P < 0.0001), and 55.9% (33/59) A/PI (P < 0.001). Among participants with <=12 years of education, 21.2% knew the leading cause of death and 49.3% knew heart attack symptoms vs 75.7% and 75.5%, respectively, for >12 years (both P < 0.0001). CONCLUSIONS: Effective prevention strategies for at-risk populations need to escalate CVD knowledge and awareness among the undereducated and minority women. PMID- 22083541 TI - Trabecular bone score (TBS): available knowledge, clinical relevance, and future prospects. AB - The diagnosis of osteoporosis rests on areal bone mineral density (BMD) measurement using DXA. Cancellous bone microarchitecture is a key determinant of bone strength but cannot be measured using DXA. To meet the need for a clinical tool capable of assessing bone microarchitecture, the TBS was developed. The TBS is a texture parameter that evaluates pixel gray-level variations in DXA images of the lumbar spine. The TBS variations may reflect bone microarchitecture. We explain the general principles used to compute the TBS, and we report the correlations between TBS and microarchitectural parameters. Several limitations of the TBS as it is used now are pointed out. We discuss data from currently available clinical studies on the ability of the TBS to identify patients with fractures and to evaluate the fracture risk. We conclude that this new index emphasizes the failure of the BMD T-score to fully capture the fragility fracture risk. However, although microarchitecture may influence the TBS, today, to the best of our understanding, there is no sufficient evidence that a TBS measurement provides reliable information on the status of the bone microarchitecture for a given patient. The TBS depends on gray-level variations and in a projectional image obtained in vivo, these variations can have many causes. Nevertheless, as clinical studies suggest that the TBS predicts the risk of fracture even after adjustment for BMD, we are encouraged to learn more about this score. Additional studies will have to be performed to assess the advantages and limitations of the TBS, in order to ensure that it is used appropriately in clinical practice. PMID- 22083544 TI - Chemical composition of ripe fruits of Rubus chamaemorus L. grown in different habitats. AB - BACKGROUND: Cloudberry (Rubus chamaemorus L.) is one of the most valuable berry producing plants because of its nutritional properties. The chemical composition and crop yield of ripe fruits of cloudberry grown wild in 10 habitats in northern Finland was analysed over two consecutive summers. For comparison, two clones of cultivated cloudberries were studied as well. RESULTS: The concentrations of citric and malic acids, alpha-tocopherol, anthocyanins and beta-carotene had notable variations between habitats. In particularly, cloudberries grown on open habitats had higher content of citric acid and less alpha-tocopherol compared to those grown on shaded sites. In a colder and rainy summer the content of anthocyanins and the unsaturation level of fatty acids were significantly higher than in a warmer and drier summer. Crop yields were higher in the warmer summer, except in open sites where yields were quite equal. CONCLUSION: Cloudberries grown in open habitats showed notable differences in chemical composition when compared to those grown on shaded sites. Results suggest that the amount of sunlight and temperature levels could be the main factors affecting crop yield and chemical composition of cloudberry. In addition, the amount of rainfall may have an effect on anthocyanin concentrations. PMID- 22083543 TI - The loss of alpha2beta1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis. AB - OBJECTIVE: Integrin alpha2beta1 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for alpha2beta1 integrin in regulating both cell attachment and expression of matrix-degrading enzymes such as matrix metalloproteinases (MMPs), mice that lack the alpha2 integrin subunit (Itga2(-/-) mice) develop normally and are fertile. We undertook this study to investigate the effect of Itga2 deficiency in 2 different mouse models of destructive arthritis: the antigen-induced arthritis (AIA) mouse model and the human tumor necrosis factor alpha (TNFalpha)-transgenic mouse model. METHODS: AIA was induced in the knee joints of Itga2(-/-) mice and wild-type controls. Human TNF transgenic mice were crossed with Itga2(-/-) mice and were assessed clinically and histopathologically for signs of arthritis, inflammation, bone erosion, and cartilage damage. MMP expression, proliferation, fibroblast attachment, and ERK activation were determined. RESULTS: Under arthritic conditions, Itga2 deficiency led to decreased severity of joint pathology. Specifically, Itga2(-/-) mice showed less severe clinical symptoms and dramatically reduced pannus formation and cartilage erosion. Mice lacking alpha2beta1 integrin exhibited reduced MMP-3 expression, both in their sera and in fibroblast-like synoviocytes (FLS), due to impaired ERK activation. Further, both the proliferation and attachment of FLS to cartilage were partially dependent on alpha2beta1 integrin in vitro and in vivo. CONCLUSION: Our findings suggest that alpha2beta1 integrin contributes significantly to inflammatory cartilage destruction by promoting fibroblast proliferation and attachment and MMP expression. PMID- 22083545 TI - Reduced field of view MRI with rapid, B1-robust outer volume suppression. AB - MRI scans are inefficient when the size of the anatomy under investigation is small relative to the subject's full extent. The field of view must be expanded, and acquisition times accordingly prolonged. Shorter scans are feasible with reduced field of view imaging (rFOV) using outer volume suppression (OVS), a magnetization preparation sequence that attenuates signal outside a region of interest (ROI). This work presents a new OVS sequence with a cylindrical ROI, short duration, and improved tolerance for B(1)+ inhomogeneity. The sequence consists of a nonselective adiabatic tipdown pulse, which provides B(1)+-robust signal suppression, and a fast 2D spiral cylindrical tipback pulse. Analysis of the Bloch equations with transverse initial magnetization reveals a conjugate symmetric constraint for tipback pulses with small flip angles. This property is exploited to achieve two-shot performance from the single-shot tipback pulse. The OVS sequence is validated in phantoms and in vivo with multislice spiral imaging at 3 T. The relative signal-to-noise ratio efficiency of the proposed sequence was 98% in a phantom and 75-90% in vivo. The effectiveness is demonstrated with cardiovascular rFOV imaging, which exhibits improved resolution and reduced artifacts compared to conventional, full field of view imaging. PMID- 22083546 TI - Involvement of calcium-sensing receptor in oxLDL-induced MMP-2 production in vascular smooth muscle cells via PI3K/Akt pathway. AB - Matrix metalloproteinase-2 (MMP-2) is constitutively expressed in vascular smooth muscle cells (VSMCs) and up-regulated in atherosclerotic lesion by various stimuli, such as oxidized low-density lipoprotein (oxLDL). Calcium-sensing receptor (CaSR) is also expressed in VSMCs, but it remains unclear whether CaSR is associated with overproduction of MMP-2 in VSMCs. In this study, the expression of MMP-2 was detected by real-time PCR and Western blot analysis, and the gelatinolytic activity of MMP-2 was measured using gelatin zymography. Our results showed that oxLDL enhanced MMP-2 expression and activity in rat aortic VSMCs in a time- and dose-dependent manner. In addition, CaSR expression was up regulated by oxLDL. Manipulating CaSR function in these cells by NPS2390 (an antagonist of CaSR) or GdCl(3) (an agonist of CaSR) affected the oxLDL-induced MMP-2 production. In VSMCs, oxLDL stimulated the rapid activation of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, as determined by Western blot analysis. Phosphorylation of Akt and MMP-2 production stimulated by oxLDL were attenuated by LY294002 (a specific inhibitor of PI3K). Activation of Akt was suppressed by NPS2390 but enhanced by GdCl(3). In contrast, oxLDL had no stimulatory effect on the phosphorylation of JNK, and pretreatment with SP600125 (an inhibitor of JNK) produced no significant effect on oxLDL-induced MMP-2 production. These results suggest that CaSR mediates oxLDL-induced MMP-2 production in VSMCs via PI3K/Akt signal pathway. PMID- 22083547 TI - Progression of apoptic signaling from mesenteric ischemia-reperfusion injury to lungs: correlation in the level of ER chaperones expression. AB - Multiple organ dysfunction syndrome (MODS) is characterized by the development of probably reversible, progressive dysfunction of vital systems in two or more organs, directly undamaged by surgery or other trauma. The organs which have the most common potential dysfunction are lungs, liver, kidneys, heart and gastrointestinal tract. The small intestine is the source of production of proinflammatory mediators leading and contributing to multiorgan failure. The endoplasmic reticulum (ER), after ischemia and post-ischemic reperfusion, is significantly involved in the activation of enterocyte apoptosis. The purpose of this study was to determine the stage of apoptosis in the lungs, initiated through inflammatory response from the small intestine. We analyzed changes in mRNA levels of pro-apoptotic genes Gadd153 (Chop) and anti-apoptotic genes Grp78 (Bip) in the small intestine wall and lung parenchyma. During experimental procedure the rats underwent 60 min of ischemia, caused by complete occlusion of the mesenteric arteria cranialis, with subsequent reperfusion and evaluation after 1 h, 24 h and 30 days (from R1, R24 to R30, respectively, each group n = 8). The gene expression levels were measured using RT-PCR followed by electrophoresis and visualization under UV. In the lungs we detected significantly lower level of expression Grp78 by 45 +/- 6.9%. This suggests that ischemic attack and subsequent reperfusion did not promote ER stress in the lungs through induction of Gadd153 expression in the small intestine. There is still no effective approach to the treatment of affected ischemic intestine tissue, to stop the processes with could eventually lead to MODS. Therefore it is necessary to study changes in the damaged tissue at the molecular level and try to suggest possible therapeutic defined routes to the protection of tissue. PMID- 22083548 TI - Arterio-venous differences in peripheral blood mononuclear cells across human adipose tissue and the effect of adrenaline infusion. AB - Recent evidence indicates that adipose tissue macrophages and lymphocytes have a major role in the pathophysiology of obesity. The arterio-venous (A-V) difference technique has been used very effectively to understand adipose tissue metabolism in humans in vivo, and we set out to investigate whether it is possible to apply and use this technique to determine A-V differences for peripheral blood mononuclear cells (PBMCs) across human adipose tissue. We used flow-cytometric analysis of arterial blood and venous blood draining upper- (abdominal) and lower body (femoral) adipose tissue depots in middle-aged volunteers (age 45+/-8 years, BMI 25.9+/-4.1 kg m(-2)). We determined A-V differences for various PBMCs. In basal conditions, there was evidence of modest retention of some PBMCs in adipose tissue, whereas the infusion of low-dose (physiological) adrenaline led to a marked release of many PBMCs (with little evidence of depot-specific differences). In addition to the demonstration that this approach is technically feasible, these results also indicate that physiological stimuli that change adrenaline concentrations and/or adipose tissue blood flow (such as physical activity) provoke the release of PBMCs from femoral and abdominal adipose depots. PMID- 22083549 TI - Study of eight GWAS-identified common variants for association with obesity related indices in Chinese children at puberty. AB - OBJECTIVE: Genome-wide association studies (GWAS) have identified some common variants associated with obesity risk in European descents. However, their influences on obesity-related indices for the Chinese children at puberty are not widely clear yet. To address this question, we conducted a study that aims to examine effects of eight previously reported GWAS single-nucleotide polymorphisms (SNPs) on four obesity-related indices in a sample of Chinese children aged 10-12 years. METHODS: Anthropometric indices were measured in 1688 children (10.8+/-0.4 years, boys=877, girls=811) from Shanghai Children's Sleep Project. Eight SNPs within the NEGR1, TMEM18, GNPDA2, MTCH2, SH2B1, FTO, MC4R and KCTD15 genes were genotyped using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Linear regression and genetic additive model were used to test for the association betweens SNPs and obesity-related indices (weight, body mass index (BMI), waist-to-height ratio and body fat). RESULTS: Only two SNPs, rs6548238 (TMEM18) and rs9939609 (FTO), were associated with all obesity-related indices with P<0.05. After adjusting for multiple tests, rs9939609 is the only one significantly associated with the indices. SNPs, rs6548238 and rs9939609 explained 0.28% (P=0.03) and 0.54% (P=0.002) variance of BMI, respectively, that are almost two-fold of the previously GWAS-reported effects. In addition, rs6548238 was associated with four indices in boys, but not in girls. In contrast, rs9939609 showed a strong association only in girls. Six other SNPs, rs2815752 (NEGR1), rs10938397 (GNPDA2), rs10838738 (MTCH2), rs7498665 (SH2B1), rs17782313 (MC4R) and rs11084753 (KCTD15), were not associated with obesity (P>0.05). CONCLUSIONS: Variants of TMEM18 and FTO are associated with obesity indices during puberty in Chinese children, but candidate SNPs of NEGR1, GNPDA2, MTCH2, SH2B1, MC4R and KCTD15 have no significant effects on obesity indices. The findings also suggest that obesity susceptibility genes may exert more obvious effects during children's puberty. In addition, gender differences may exist in various obesity-related genes. PMID- 22083550 TI - Altered expression of gustatory-signaling elements in gastric tissue of morbidly obese patients. AB - OBJECTIVE: Sensing of nutrients in the stomach is of crucial importance for the regulation of ingestive behavior especially in the context of metabolic dysfunctions such as obesity. Cells in the gastric mucosa with taste-signaling elements are considered as candidates for sensing the composition of ingested food and consequently modulate gastrointestinal processes. To assess whether obesity might have an impact on gastric chemosensory cells, gastric tissue samples from morbidly obese patients and normal-weight subjects were compared using a reverse transcriptase (RT)-PCR, qPCR and immunohistochemical approach. RESULTS: Analysis of biopsy tissue samples from human stomach revealed that transcripts for the taste-signaling elements, including the receptor T1R3 involved in the reception of amino acids and carbohydrates, the fatty acid receptor GPR120, the G protein gustducin, the effector enzyme PLCbeta2 and the ion channel TRPM5 are present in the human gastric mucosa and led to the visualization of candidate chemosensory cells in the stomach expressing gustatory marker molecules. RT-PCR and qPCR analyses indicated striking differences in the expression profiles of specimens from obese subjects compared with controls. For GPR120, gustducin, PLCbeta2 and TRPM5 the expression levels were increased, whereas for T1R3 the level decreased. Using TRPM5 as an example, we found that the higher expression level was associated with a higher number of TRPM5 cells in gastric tissue samples from obese patients. This remarkable change was accompanied by an increased number of ghrelin-positive cells. CONCLUSIONS: Our findings argue for a relationship between the amount of food intake and/or the energy status and the number of candidate chemosensory cells in the gastric mucosa. PMID- 22083551 TI - Leptin-deficient (ob/ob) mouse ovaries show fatty degeneration, enhanced apoptosis and decreased expression of steroidogenic acute regulatory enzyme. AB - OBJECTIVE: Leptin-deficient (ob/ob) mice are obese and infertile. Dysfunctions of the ovaries are preferentially related to leptin-deficiency. DESIGN: Morphological and molecular biological obesity-dependent changes in ob/ob ovaries. SUBJECTS: Ovaries were obtained from three-month-old mice either homozygote (ob/ob) and heterozygote (ob/+) or wild-type (C57BL6, WT) for the investigation by light and electron microscopy, as well as for western blot analysis of lectin-like oxidised low density lipoprotein receptor (LOX-1), Toll like receptor 4 (TLR4), CD36, cleaved caspase-3, microtubule-associated protein light chain 3 (LC3), and the steroidogenic acute regulatory protein (StAR). RESULTS: Compared with control ovaries with corpora lutea, ob/ob ovaries lacked corpora lutea, follicular atresia was at a higher rate; lipid droplets accumulated in follicle cells and in the oocyte with damaged mitochondria; the basement membrane of follicles was thickened. LOX-1 and CD36 expressions were comparable for all three groups. Ob/ob ovaries showed significantly higher levels of TLR4 and cleaved caspase-3 than the ones from the control groups. The high LC3 II/I ratio in the WT and ob/+ ovaries was related to the presence of corpora lutea. The StAR protein was lower in the ob/ob ovaries signifying reduced steroidogenesis. CONCLUSIONS: Excessive lipid storage causes disorders of ovarian function in ob/ob mice. The local lipid overload leads to advanced follicular atresia with apoptosis and defect steroidogenesis. We suggest that the changes in lipid metabolism lead to increased oxidative stress and thereby, they are an important reason of anovulation and infertility. PMID- 22083553 TI - Computer-based route-definition system for peripheral bronchoscopy. AB - Multi-detector computed tomography (MDCT) scanners produce high-resolution images of the chest. Given a patient's MDCT scan, a physician can use an image-guided intervention system to first plan and later perform bronchoscopy to diagnostic sites situated deep in the lung periphery. An accurate definition of complete routes through the airway tree leading to the diagnostic sites, however, is vital for avoiding navigation errors during image-guided bronchoscopy. We present a system for the robust definition of complete airway routes suitable for image guided bronchoscopy. The system incorporates both automatic and semiautomatic MDCT analysis methods for this purpose. Using an intuitive graphical user interface, the user invokes automatic analysis on a patient's MDCT scan to produce a series of preliminary routes. Next, the user visually inspects each route and quickly corrects the observed route defects using the built-in semiautomatic methods. Application of the system to a human study for the planning and guidance of peripheral bronchoscopy demonstrates the efficacy of the system. PMID- 22083552 TI - Depression and anxiety diagnoses are not associated with delayed resolution of abnormal mammograms and pap tests among vulnerable women. AB - BACKGROUND: Delays in care after abnormal cancer screening contribute to disparities in cancer outcomes. Women with psychiatric disorders are less likely to receive cancer screening and may also have delays in diagnostic resolution after an abnormal screening test. OBJECTIVE: To determine if depression and anxiety are associated with delays in resolution after abnormal mammograms and Pap tests in a vulnerable population of urban women. DESIGN: We conducted retrospective chart reviews of electronic medical records to identify women who had a diagnosis of depression or anxiety in the year prior to the abnormal mammogram or Pap test. We used time-to-event analysis to analyze the outcome of time to resolution after abnormal cancer screening, and Cox proportional hazards regression modeling to control for confounding. PARTICIPANTS: Women receiving care in six Boston-area community health centers 2004-2005: 523 with abnormal mammograms, 474 with abnormal Pap tests. RESULTS: Of the women with abnormal mammogram and pap tests, 19% and 16%, respectively, had co-morbid depression. There was no difference in time to diagnostic resolution between depressed and not-depressed women for those with abnormal mammograms (aHR = 0.9, 95 CI 0.7,1.1) or Pap tests (aHR = 0.9, 95 CI 0.7,1.3). CONCLUSIONS: An active diagnosis of depression and/or anxiety in the year prior to an abnormal mammogram or Pap test was not associated with a prolonged time to diagnostic resolution. Our findings imply that documented mood disorders do not identify an additional barrier to resolution after abnormal cancer screening in a vulnerable population of women. PMID- 22083554 TI - Type 2 diabetes mellitus and prognosis in early stage breast cancer women. AB - It has been suggested that type 2 diabetes mellitus may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The aim of this study was to determine the impact of diabetes on disease-free survival (DFS) following mastectomy for breast cancer patients. The cases included in this retrospective study were selected from breast cancer women who had undergone mastectomy and completed adjuvant chemotherapy from 1998 to 2010. Patients were classified into two groups: diabetic and non-diabetic. Patients' age, sex, menopausal status, body mass index (BMI), histopathological features, tumor size, lymph node involvement, hormone receptor and HER2-neu status, and treatment types were recorded. There were 483 breast cancer patients included in the study. Postmenopausal patients' rate (53.7% vs. 36.8%, P = 0.016) and mean BMI levels were statistically higher (32.2 vs. 27.9, P = 0.007) in diabetic patients. There was no statistical difference for histological subgroup, grade, ER and PR positivity, HER2-neu overexpression rate, and tumor size between the diabetic and non-diabetic group. Lymph node involvements were statistically higher in diabetic patients compared with non-diabetic patients (P = 0.013). Median disease-free survival is 81 months (95% CI, 61.6-100.4) in non-diabetic patients and 36 months (95% CI, 13.6-58.4) in diabetic patients (P < 0.001). The odds ratio of recurrence was significantly increased in those with HER2-neu overexpression and lymph node involvement and decreased with PR-positive tumors. Our results suggest that diabetes is an independent prognostic factor for breast cancer. PMID- 22083556 TI - Differential prognostic effect of revascularization according to a simple comorbidity index in high-risk non-ST-segment elevation acute coronary syndrome. AB - BACKGROUND: Data on the effect of revascularization on outcome in patients with high-risk non-ST-segment elevation acute coronary syndrome (NSTEACS) and significant comorbidities are scarce. Recently, a simple comorbidity index (SCI) including 5 comorbidities (renal failure, dementia, peripheral artery disease, heart failure, and prior myocardial infarction [MI]) has shown to be a useful tool for risk stratification. Nevertheless, therapeutic implications have not been derived. HYPOTHESIS: We sought to evaluate the prognostic effect attributable to revascularization in NSTEACS according the SCI score. METHODS: We included 1017 consecutive patients with NSTEACS. The effect of revascularization on a combined end point of all-cause mortality or nonfatal MI was evaluated by Cox regression according to SCI categories. RESULTS: A total of 560 (55.1%), 236 (23.2%), and 221 (21.7%) patients showed 0, 1, and >=2 points according to the SCI, respectively. Coronary angiography was performed in 725 patients (71.5%), and 450 patients (44.3%) underwent revascularization. During a median follow-up of 16 months (interquartile range, 12-36 months), 305 (30%) patients experienced the combined end point (202 deaths [19.9%] and 170 MIs [16.7%]). In multivariate analysis, a differential prognostic effect of revascularization was observed comparing SCI >=2 vs 0 (P for interaction = 0.008). Thus, revascularization was associated with a greater prognostic benefit in patients with SCI >=2 (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.29-0.89), P = 0.018), whereas no significant benefit was observed in those with 0 and 1 point (HR: 1.31, 95% CI: 0.88-1.94, P = 0.171 and HR: 1.11, 95% CI: 0.70-1.76, P = 0.651, respectively). CONCLUSIONS: In NSTEACS, the SCI score appears to be a useful tool for identifying a subset of patients with a significant long-term death/MI risk reduction attributable to revascularization. PMID- 22083558 TI - Discovery of potential antipsychotic agents possessing pro-cognitive properties. AB - Current antipsychotic drug therapies for schizophrenia have limited efficacy and are notably ineffective at addressing the cognitive deficits associated with this disorder. The present study was designed to develop effective antipsychotic agents that would also ameliorate the cognitive deficits associated with this disease. In vitro studies comprised of binding and functional assays were utilized to identify compounds with the receptor profile that could provide both antipsychotic and pro-cognitive features. Antipsychotic and cognitive models assessing in vivo activity of these compounds included locomotor activity assays and novel object recognition assays. We developed a series of potential antipsychotic agents with a novel receptor activity profile comprised of muscarinic M(1) receptor agonism in addition to dopamine D(2) antagonism and serotonin 5-HT(2A) inverse agonism. Like other antipsychotic agents, these compounds reverse both amphetamine and dizocilpine-induced hyperactivity in animals. In addition, unlike other antipsychotic drugs, these compounds demonstrate pro-cognitive actions in the novel object recognition assay. The dual attributes of antipsychotic and pro-cognitive actions distinguish these compounds from other antipsychotic drugs and suggest that these compounds are prototype molecules in the development of novel pro-cognitive antipsychotic agents. PMID- 22083560 TI - Established HPLC fraction analysis to predict furanocoumarin-based herb-drug metabolic interactions. AB - An attempt was made in this study to predict the potential for metabolic interactions of herbal extracts of drugs from their chromatographic profiles in reverse-phase high-performance liquid chromatography (RP-HPLC). Twenty-nine structurally related furanocoumarin compounds with known inhibitory interactions with cytochrome P450 3A (CYP3A), which is important for phase-I drug metabolism, were selected as a model system. A sigmoidal relationship was established between the CYP3A inhibitory potency (y) and the RP-HPLC total peak response unit (R(u), x) as y = 85.36 x (14.86 + x)-1 with a correlation coefficient of 0.63. The sigmoidal curve could be divided into three ranges designated low, medium and high risk that were used to indicate the relative inhibitory potency of the metabolic interactions of herbs or traditional Chinese herb medicines with CYP3A. These predictive classifications provide information or might be useful for 'risk category' decisions concerning herb-drug interactions. PMID- 22083559 TI - Importance of the Kir6.2 N-terminus for the interaction of glibenclamide and repaglinide with the pancreatic K(ATP) channel. AB - The pancreatic K(ATP) channel, SUR1/Kir6.2, couples insulin secretion to the plasma glucose level. The channel is an octamer with four Kir6.2 subunits forming the pore and four sulphonylurea receptors (SUR1) regulating channel activity. SUR1 is an ABC protein with adenosine triphosphate (ATP)ase activity which activates the channel. It also contains the binding site for antidiabetic drugs like glibenclamide and repaglinide which close the channel by disrupting the stimulatory effect SUR-ATPase (MgATP-dependent) and by stabilising a long-lived closed channel state (MgATP-independent). In this study, we examined the effects of progressive truncation of the Kir6.2 N-terminus up to 20 amino acids on equilibrium binding and channel closure by glibenclamide and repaglinide, on the channel activating effect of the opener, 6-chloro-3-(1-methylcyclobutyl)amino-4H thieno[3,2-e]-1,2,4thiadiazine 1,1-dioxide (NNC 55-0462), and on the binding kinetics of [(3)H]glibenclamide. Kir and SUR were transiently coexpressed in HEK cells and [(3)H]glibenclamide binding and patch-clamp experiments were performed in whole cells at 37 degrees C and in isolated inside/out patches at 22 degrees C. Truncation of the first 5 N-terminal amino acids abolished most of the affinity increase for glibenclamide and repaglinide that is produced by the association of Kir6.2 with SUR1. Progressive truncation continuously reduced the potency and efficacy of these drugs in closing the channel and impaired the ability to stabilise the closed state more than the ability to disrupt channel stimulation by SUR-ATPase. The effects of NNC 55-0462 were unchanged. Progressive truncation also speeded up dissociation of [(3)H]glibenclamide from the channel when dissociation was induced by an excess of (unlabelled) glibenclamide. This suggests the existence of a putative low affinity glibenclamide site on the channel whose affinity increases upon truncation. The data show that progressive truncation of the Kir6.2 N-terminus impairs the transduction of drug binding into channel closure more strongly than drug binding but leaves the effect of the opener NNC 55-0462 unchanged. PMID- 22083561 TI - Noise and ischemic heart disease. PMID- 22083562 TI - Differences in apparent diffusion coefficients of brain metabolites between grey and white matter in the human brain measured at 7 T. AB - Diffusion weighted spectroscopy can provide microstructural information that is specific to compartmental geometry. So far, in human brain, apparent diffusion coefficients (ADCs) of only the metabolites N-acetyl aspartate, creatine (tCr) and choline (tCho) have been assessed. High field MR at 7 T allows the collection and analysis of diffusion weighted spectroscopy data of additional metabolites of interest such as glutamate (Glu), N-acetyl aspartyl glutamate, and glutamine (Gln), which are of interest due to their different compartmentalization and role in brain physiology. In this study, we performed (1)H diffusion weighted spectroscopy at 7 T using a diffusion-weighted PRESS sequence in parietal white matter (n = 6) and occipital grey matter (n = 7). Data were analyzed using the LCmodel. ADCs could reliably be obtained of N-acetyl aspartate, tCr, tCho, Glu, Gln in grey and white matter, and N-acetyl aspartyl glutamate in white matter. Significant differences in ADC values were observed between grey and white matter for all metabolites. ADCs in grey matter were consistently lower than in white matter. These differences can probably be attributed to different compartmentalization as well as to the differential impact of diffusion time on ADC of different molecules under conditions of restricted diffusion. PMID- 22083563 TI - Young women with family history of breast cancer and their risk factors for benign breast disease. AB - BACKGROUND: Breast cancer (BC) patients wonder how their daughters might reduce their risk. The authors investigated childhood/adolescent risk factors for benign breast disease (BBD), a well-documented risk factor for BC, among girls with a family history. METHODS: GUTS (the Growing Up Today Study) includes females, aged 9 to 15 years in 1996, who completed annual questionnaires during 1996 to 2001, then in 2003, 2005, and 2007. Participants provided information regarding alcohol, menarche, height, and body mass index (BMI; kg/m(2)). Peak height growth velocity (PHV; in./y) was estimated from longitudinal heights. On 2005-2007 surveys, 6888 women (18-27 years old) reported whether they were diagnosed with biopsy-confirmed BBD (n = 67 cases); 6741 women (noncases) reported no BBD. Participants' mothers reported their own biopsy-confirmed BBD and BC, and BC in their sisters and mothers. Stratified by family history, logistic models investigated BBD risk factors. RESULTS: Young women whose mothers or aunts had BC were more likely to be diagnosed with BBD (odds ratio [OR], 2.34; P = .01), as were those with maternal BBD (OR, 1.59; P = .095). Adolescents with BC family history (mother, aunt, grandmother) who consumed alcohol (7 drinks/wk) doubled their BBD risk (OR, 2.28; P = .01), similar to those with maternal BBD (OR, 1.96; P = .02). Girls whose mother or aunt had BC saw their BBD risk elevated with higher PHV (OR, 1.82 [inch/yr]; P = .05). Among girls with no family history, BBD risk appeared to be related to other factors: childhood BMI, adolescent waist circumference, and adult height. CONCLUSIONS: Adolescents with family history may reduce their risk by avoiding alcohol. Separate risk factors were observed among girls with family history versus girls with no family history, possibly reflecting different causes of BC. PMID- 22083564 TI - Growth, yield and seed composition of native Australian legumes with potential as grain crops. AB - BACKGROUND: Many Australian native legumes grow in arid and nutrient-poor environments. Yet few Australian herbaceous legumes have been investigated for domestication potential. This study compared growth and reproductive traits, grain yield and seed composition of 17 native Australian legumes with three commercial grain legumes. RESULTS: Seed yields of seven native legumes were > 40% of Cicer arietnum, with highest seed yields and harvest indices in Glycine sp. (14.4 g per plant, 0.54 g g(-1) ) and Lotus cruentus (10.2 g per plant, 0.65 g g( 1) ). Five native species flowered earlier than field pea (Pisum sativa) (109 days), though many were slower to flower and set seed. Largest seeds were found in Glycine canescens (17 mg), with seed of other native species 14 times smaller than commercial cultivars. Seed composition of many native legumes was similar to commercial cultivars (200-330 g protein kg(-1) dry weight (DW), 130-430 g dietary fibre kg(-1) DW). Two Cullen species had high fat content (>110 g kg(-1) DW) and Trigonella sauvissima had the highest crude protein content (370 g kg(-1) DW). CONCLUSION: The seed composition and reproductive traits of some wild native Australian legumes suggest they could offer potential as grain crops for soils and environments where the current grain legumes are uneconomic. Further evaluation of genetic diversity, especially for seed size, overall productivity, and reproductive development is needed. PMID- 22083565 TI - A new route towards nanoporous TiO2 as powders or thin films from the thermal treatment of titanium-based hybrid materials. AB - Calcination of cyclopentadienyltitanium-based organic-inorganic hybrid materials at 450-500 degrees C led to the formation of anatase titanium dioxide as white powders consisting of a porous network of aggregated nanoparticles, the nanoporosity detected being related to the inter-particle space. Depending on the calcination temperatures, the surface area of the titanium dioxide particles varied from 65 to 158 m(2) g(-1). PMID- 22083567 TI - Comprehensive approach to restoration of function in patients with radiation induced pharyngoesophageal stenosis: report of 31 patients and proposal of new classification scheme. AB - BACKGROUND: The treatment for upper aerodigestive tract malignancy with external beam radiation therapy and chemotherapy can result in a "cure," yet result in pharyngoesophageal (PE) stenosis. To improve communication, compare therapeutic results, and assist in treatment planning, we developed a new classification system to describe PE stenoses. Additionally, we analyzed our 6-year experience. METHODS: The new classification system was defined and used to assess patient management. RESULTS: Thirty-one patients underwent treatment for PE stenoses using: 4 rendezvous dilations, 3 regional, and 24 free tissue transfers. Overall success was based on airway status, speech, and swallowing outcomes. CONCLUSION: Classification of posttreatment stenoses has been applied to this patient group. It is effective in defining the problem and considerations related to treatment planning and surgical access when augmentation pharyngoplasty is required. Patients with an intact larynx have many issues that make recovery of function less consistent, despite segment restoration. PMID- 22083566 TI - Exploratory investigation on nitro- and phospho-proteome cerebellum changes in hyperammonemia and hepatic encephalopathy rat models. AB - Hepatic encephalopathy (HE) is a neurological disease associated with hepatic dysfunction. Current knowledge suggests that hyperammonemia, related to liver failure, is a main factor contributing to the cerebral alterations in HE and that hyperammonemia might impair signal transduction associated with post translational modification of proteins such as tyrosine-nitration and phosphorylation. However, the molecular bases of the HE remain unclear and very little is known about the occurrence of post-translational modification on in vivo proteins. In this exploratory study we look for evidence of post-translation modifications of proteins in the cerebellum of experimental HE rat models using a proteomic approach. For the first time we showed that hyperammonemia without liver failure (HA rats) and experimental HE with liver failure due to portacaval shunt (PCS rats) lead to a reduced protein nitration in rat cerebellum, where the undernitrated proteins were involved in energy metabolism and cytoskeleton remodelling. Moreover we showed that tyrosine nitration loss of these proteins was not necessarily associated to a change in their phosphorylation state as result of the disease. Interestingly the rat cerebellum phosphoproteome was mainly perturbed in PCS rats, whereas HA rats did not shown appreciable changes in their phosphoprotein profile. Since the protein nitration level decreased similarly in the cerebellum of both HA and PCS rats, this implies that the two disease models share common effects but also present some differential signalling effects in the cerebellum of the same animals. This study highlights the interest for studying the concerted action of multiple signalling pathways in HE development. PMID- 22083568 TI - Differences in serum zn levels in acutely ill and recovered adolescents and young adults with anorexia nervosa--a pilot study. AB - Preliminary evidence suggests that changes in zinc (Zn) metabolism are associated with anorexia nervosa (AN). However, data are scarce regarding potential differences in serum Zn concentrations in adolescent and young adult patients with AN. It was the aim of the present pilot study to compare serum Zn concentrations between acutely ill and remitted adolescent and young adult female patients with AN and female controls. Zn concentrations were higher in remitted compared with acutely ill patients. Zn concentrations were also higher in remitted patients compared with controls, but there was no significant difference in Zn concentrations between acutely ill patients and controls. The present study provides preliminary evidence for differences in serum Zn status in recovered patients with AN. These differences are likely influenced by reported food preferences, in particular as regards Ca2+ and phosphorus-containing foods. However, because of limited statistical power, future research involving larger samples is necessary. PMID- 22083569 TI - Dramatic increases in carotid stenting despite nonconclusive data. PMID- 22083570 TI - Goals of care for hip fracture: promoting independence and reducing mortality. PMID- 22083571 TI - Atrial fibrillation in the otherwise healthy patient: still a cause for concern. PMID- 22083572 TI - Growth in dementia-associated hospitalizations among the oldest old in the United States: implications for ethical health services planning. PMID- 22083573 TI - Hearing loss prevalence in the United States. PMID- 22083574 TI - Invited commentary--creating the future of aging. PMID- 22083575 TI - Psychological distress as a risk factor for dementia death. PMID- 22083576 TI - More is less. PMID- 22083577 TI - QRS morphology rather than QRS duration for predicting CRT response. PMID- 22083578 TI - Acid suppressive therapy in noncritically ill patients. PMID- 22083579 TI - Disclosure of outside income. PMID- 22083580 TI - Autonomic mechanisms associated with heart rate and vasoconstrictor reserves. AB - INTRODUCTION: Hemorrhage is accompanied by baroreflex-mediated tachycardia and vasoconstriction. The difference between baseline and maximum responses is defined as the heart rate (HR) and vasoconstrictor 'reserve'. OBJECTIVE: To test the hypothesis that higher HR and vasoconstrictor reserves in subjects with high tolerance (HT) to central hypovolemia is associated with greater reserve for sympathoexcitation and vagal withdrawal compared with low tolerant (LT) subjects. METHODS: R-R intervals (RRI), systolic arterial pressure (SAP), estimated stroke volume, and muscle sympathetic nerve activity (MSNA) were measured during lower body negative pressure (LBNP) designed to induce pre-syncope. Subjects with tolerance <= 60 mmHg LBNP were classified as LT (n = 22) while subjects who tolerated LBNP levels >60 mmHg were classified as HT (n = 56). Spontaneous cardiac baroreflex sensitivity (BRS) was assessed via RRI-SAP down-down sequences. RESULTS: HR reserve in HT subjects (+52 +/- 2 bpm) was twofold greater (P < 0.001) than that in LT subjects (+27 +/- 3 bpm). Vasoconstrictor reserve in the HT group (+3.4 +/- 0.5 pru) was greater (P = 0.04) than that of the LT group (+1.9 +/- 0.3 pru). HT subjects demonstrated greater (P <= 0.03) BRS reserve ( 14.2 +/- 1.8 ms/mmHg) and MSNA reserve (+41 +/- 2 bursts/min) compared with LT subjects (-7.4 +/- 1.7 ms/mmHg and +26 +/- 7 bursts/min). INTERPRETATION: Our data support the hypothesis that greater physiological reserve capacity for tachycardia and vasoconstriction related to high tolerance to central hypovolemia is associated with greater reserves for sympathoexcitation and cardiac vagal withdrawal. PMID- 22083581 TI - An embryonic stem cell-based system for rapid analysis of transcriptional enhancers. AB - With the growing use of genome-wide screens for cis-regulatory elements, there is a pressing need for platforms that enable fast and cost-effective experimental validation of identified hits in relevant developmental and tissue contexts. Here, we describe a murine embryonic stem cell (ESC)-based system that facilitates rapid analysis of putative transcriptional enhancers. Candidate enhancers are targeted with high efficiency to a defined genomic locus via recombinase-mediated cassette exchange. Targeted ESCs are subsequently differentiated in vitro into desired cell types, where enhancer activity is monitored by reporter gene expression. As a proof of principle, we analyzed a previously characterized, Sonic hedgehog (Shh)-dependent, V3 interneuron progenitor (pV3)-specific enhancer for the Nkx2.2 gene, and observed highly specific enhancer activity. Given the broad potential of ESCs to generate a spectrum of cell types, this system can serve as an effective platform for the characterization of gene regulatory networks controlling cell fate specification and cell function. PMID- 22083582 TI - Polydimethylsiloxane-functionalized monolithic silica column for reversed-phase capillary liquid chromatography. AB - A polydimethylsiloxane (PDMS)-modified monolithic silica column was prepared for performing reversed-phase capillary liquid chromatography. The prepared PDMS column has a permeability of 6.4*10(-14) m(2) with a plate height <9.2 MUm. Alkylbenzenes and polycyclic aromatic hydrocarbons (PAHs) were well separated with the PDMS stationary phase, which exhibited similar selectivity and separation mechanism to that of octadecyl stationary phase. The hydrophobic interactions between the analytes and the PDMS stationary phase mainly play the roles for the separation of alkylbenzenes and PAHs. The characteristics of the PDMS column for the separation of alkylbenzenes and PAHs demonstrated that it would be a promising alternative to the octadecyl column. PMID- 22083584 TI - Peritoneal sarcomatosis associated with telemetry implants in Sprague Dawley CD rats: a review of eight cases. AB - Surgical implantation of radiotelemetric transmitters is a current practice to collect a variety of physiological parameters in unrestrained laboratory animals, and in rodents in particular. In this study, the incidence of peritoneal sarcomatosis arising secondary to surgically implanted telemetry devices (< 15% of implanted Sprague Dawley rats) is considered to represent a significant issue for both animal welfare and data validity in affected animals. Macroscopically, the telemetry-associated fibrosarcomas spread along the visceral and parietal peritoneum and mesentery surrounding abdominal organs. The histologic morphology of these sarcomas was typically an undifferentiated sarcoma, although well differentiated fibrosarcomas and telangiectatic and pleomorphic variants were noted. Using special stains such as Masson's Trichrome demonstrated a collagenous extracellular matrix in 50% of these rats, which is consistent with a fibroblastic origin. Immunohistochemical studies clearly delineated the mesenchymal components of the sarcomas (fibroblasts and smooth muscle cells); one case, however, was diagnosed as an osteosarcoma. PMID- 22083583 TI - Intrasplenic transplantation of isolated adult rat hepatocytes: sex-reversal and/or suppression of the major constituent isoforms of cytochrome P450. AB - Adult male and female rat hepatocytes were individually transplanted into the spleens of adult male and female rats. The recipients were euthanized at either eight, sixteen, thirty, or forty-five weeks following transplantation, at which time hepatic and splenic levels of liver-specific rat albumin mRNA as well as sex dependent transcript levels of CYP2C11, -2C12, -2C7, -2A1, and -3A2-which accounts for > 60% of the total concentration of hepatic constituent cytochrome P450-were determined. Whereas the pre-infused hepatocytes expressed their expected cytochrome P450 sexual dimorphisms (female-specific CYP2C12, male specific CYP3A2, and female-predominant CYP2A1), their post-transplantational competence now reflected the sexual dimorphisms of the recipient (as observed in the host's liver), which supports the concept that the sex-dependent growth hormone circulating profiles are the determinants regulating the expression levels of hepatic cytochrome P450. Also expressed at normal concentrations in the pre-infused hepatocytes, male-specific CYP2C11 and female-predominant CYP2C7 were inexplicably undetectable in the spleens of both recipient males and females, regardless of the sex of the donor hepatocytes, almost one year after transplantation. PMID- 22083586 TI - Small molecule immunomodulatory drugs: challenges and approaches for balancing efficacy with toxicity. AB - As the molecular pathobiology of immunologically based diseases, such as rheumatoid arthritis, has become clearer, pharmaceutical researchers have responded with highly efficacious and selective biological compounds. In contrast to older, nonspecific small-molecule therapeutics, the exquisite species sensitivity of monoclonal antibodies has introduced new challenges to preclinical safety studies. Repeated exposure of animals to biopharmaceutical compounds tends to be restricted in the species in which these compounds have pharmacological action, and it tends to stimulate antidrug immune responses with acceleration of clearance, thereby limiting the duration of repeat-dose studies and potentially resulting in hypersensitivity reactions. Thus, the safety testing of biopharmaceutical compounds has necessitated the use of relatively short-term studies in rodents, whereas nonhuman primates have become the primary tool for large-animal, repeat-dose studies. However, as the number of highly targeted and efficacious small-molecule immunomodulators rapidly increases, these molecules will be developed in a manner similar to that of other small molecules with regard to safety assessment. Because such approaches inherently push drug levels to achieve maximally tolerated doses, the pharmacologic specificity of these new small-molecule drugs may be lost as they affect additional receptors and pathways. Therefore, toxicologic pathologists must refamiliarize themselves with the consequences of profound immunosuppression in species other than nonhuman primates. The interrelationships of cytokine signaling and receptor biology are complex, highly integrated, and at times paradoxical, and the loss of specificity at high doses may result in unforeseen consequences caused by the impact on complex down-stream pathways that culminate in exaggerated and adverse responses. The species specificity of such responses may not be inherently familiar or anticipated. PMID- 22083585 TI - Comparative long-term preclinical safety evaluation of two glatiramoid compounds (glatiramer Acetate, Copaxone(R), and TV-5010, protiramer) in rats and monkeys. AB - Glatiramer acetate (GA), the active ingredient in Copaxone(r), is a complex mixture of polypeptides used for the treatment of relapsing remitting multiple sclerosis. Glatiramoids are related mixtures that may differ in some characteristics of the prototype molecule. Our aim is to describe the long-term toxicity studies with protiramer (TV-5010), a new glatiramoid, in comparison with similar studies conducted with GA. The toxicity of twice-weekly subcutaneous injections of protiramer to Sprague-Dawley rats (twenty-six weeks) and cynomolgus monkeys (fifty-two weeks) was compared with similar studies done with daily subcutaneous injections of GA. Daily treatment with GA was safe and well tolerated, without systemic effects or death. Protiramer administration was not as well tolerated as GA and led to dose- and time-related mortalities, probably mediated through severe injection-site lesions both in rats and in monkeys. Bridging fibrosis in the liver and severe progressive nephropathy were seen in rats. A dose-related increase in eosinophils was observed in monkeys. The protiramer toxicity studies show that minor variations in the manufacturing of glatiramoids may lead to significant toxic effects. It is therefore essential that the safety of any new glatiramoid be studied in long-term preclinical studies before exposing humans. PMID- 22083587 TI - Association of coronary artery calcium with severity of myocardial ischemia in left anterior descending, left circumflex, and right coronary artery territories. AB - BACKGROUND: An increasing coronary artery calcium score is associated with a higher likelihood of myocardial ischemia. HYPOTHESIS: The association of the coronary calcium score with myocardial ischemia in different coronary arteries needed to be investigated. METHODS: We correlated the coronary artery calcium (CAC) score with the severity of myocardial ischemia diagnosed by myocardial perfusion imaging in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) territories in 206 patients, mean age 66 years, without cardiac stents or coronary artery surgery. RESULTS: The mean CAC score in the LAD coronary artery was 160 +/- 218 in patients with no or mild ischemia and 336 +/- 379 in patients with moderate or severe ischemia (P = 0.039). The mean CAC score in the LCX coronary artery was 57 +/- 117 in patients with no or mild ischemia and 161 +/- 191 in patients with moderate or severe ischemia (P = 0.018). The mean CAC score in the RCA was 114 +/- 237 in patients with no or mild ischemia and 261 +/- 321 in patients with moderate or severe ischemia (P = 0.045). Stepwise linear regression analysis showed that male gender (P < 0.0001), age (P < 0.0001), and moderate or severe ischemia (P = 0.023) were significantly associated with high LAD coronary artery CAC scores. Male gender (P < 0.0001), age (P = 0.0002), and moderate or severe ischemia (P = 0.006) were significantly associated with high LCX coronary artery CAC scores. Male gender (P < 0.0001) and age (P < 0.0001) were significantly associated with high RCA CAC scores. CONCLUSIONS: Higher CAC scores are significantly associated with moderate or severe ischemia in the LAD and LCX coronary arteries. PMID- 22083588 TI - HDXFinder: automated analysis and data reporting of deuterium/hydrogen exchange mass spectrometry. AB - Hydrogen/deuterium exchange in combination with mass spectrometry (H/D MS) is a sensitive technique for detection of changes in protein conformation and dynamics. However, wide application of H/D MS has been hindered, in part, by the lack of computational tools necessary for efficient analysis of the large data sets associated with this technique. We report a novel web-based application for automatic analysis of H/D MS experimental data. This application relies on the high resolution of mass spectrometers to extract all isotopic envelopes before correlating these envelopes with individual peptides. Although a fully automatic analysis is possible, a variety of graphical tools are included to aid in the verification of correlations and rankings of the isotopic peptide envelopes. As a demonstration, the rate constants for H/D exchange of peptides from rabbit muscle pyruvate kinase are mapped onto the structure of this protein. PMID- 22083589 TI - Detection and characterization of low abundance glycopeptides via higher-energy C trap dissociation and orbitrap mass analysis. AB - Broad-scale mass spectrometric analyses of glycopeptides are constrained by the considerable complexity inherent to glycoproteomics, and techniques are still being actively developed to address the associated analytical difficulties. Here we apply Orbitrap mass analysis and higher-energy C-trap dissociation (HCD) to facilitate detailed insights into the compositions and heterogeneity of complex mixtures of low abundance glycopeptides. By generating diagnostic oxonium product ions at mass measurement errors of <5 ppm, highly selective glycopeptide precursor ion detections are made at sub-fmol limits of detection: analyses of proteolytic digests of a hen egg glycoprotein mixture detect 88 previously uncharacterized glycopeptides from 666 precursor ions selected for MS/MS, with only one false positive due to co-fragmentation of a non-glycosylated peptide with a glycopeptide. We also demonstrate that by (1) identifying multiple series of glycoforms using high mass accuracy single stage MS spectra, and (2) performing product ion scans at optimized HCD collision energies, the identification of peptide + N-acetylhexosamine (HexNAc) ions (Y1 ions) can be readily achieved at <5 ppm mass measurement errors. These data allow base peptide sequences and glycan compositional information to be attained with high confidence, even for glycopeptides that produce weak precursor ion signals and/or low quality MS/MS spectra. The glycopeptides characterized from low fmol abundances using these methods allow two previously unreported glycosylation sites on the Gallus gallus protein ovoglycoprotein (amino acids 82 and 90) to be confirmed; considerable glycan heterogeneities at amino acid 90 of ovoglycoprotein, and amino acids 34 and 77 of Gallus gallus ovomucoid are also revealed. PMID- 22083590 TI - Formation and fragmentation of radical peptide anions: insights from vacuum ultra violet spectroscopy. AB - We have studied the photodissociation of gas-phase deprotonated caerulein anions by vacuum ultraviolet (VUV) photons in the 4.5 to 20 eV range, as provided by the DESIRS beamline at the synchrotron radiation facility SOLEIL (France). Caerulein is a sulphated peptide with three aromatic residues and nine amide bonds. Electron loss is found to be the major relaxation channel at every photon energy. However, an increase in the fragmentation efficiency (neutral losses and peptide backbone cleavages) as a function of the energy is also observed. The oxidized ions, generated by electron photodetachment were further isolated and activated by collision (CID) in a MS(3) scheme. The branching ratios of the different fragments observed by CID as a function of the initial VUV photon energy are found to be independent of the initial photon energy. Thus, there is no memory effect of the initial excitation energy on the fragmentation channels of the oxidized species on the time scale of our tandem MS experiment. We also report photofragment yields as a function of photon energy for doubly deprotonated caerulein ions, for both closed-shell ([M-2H](2-)) non-radical ions and open shell ([M-3H](2-*)) radical ions. These latter ions are generated by electron photodetachment from [M-3H](3-) precursor ions. The detachment yield increases monotonically with the energy with the appearance of several absorption bands. Spectra for radical and non-radical ions are quite similar in terms of observed bands; however, the VUV fragmentation yield is enhanced by the presence of a radical in caerulein peptides. PMID- 22083591 TI - Individual differences in the effects of environmental stimuli on cocaine choice in socially housed male cynomolgus monkeys. AB - RATIONALE: Studies in laboratory animals have demonstrated an influence of environmentally derived stress and enrichment on the reinforcing effects of stimulants. OBJECTIVE: To characterize the effects of acute exposure to ethologically valid environmental stimuli on the reinforcing strength of cocaine relative to food in socially housed monkeys. MATERIALS AND METHODS: Choice between cocaine and food was assessed in subsets of 16 socially housed (4/pen) male cynomolgus monkeys immediately after the following manipulations: (1) treats placed in home cage, (2) a 10-min exposure to a rubber snake, or (3) 3 to 7 days of living in a larger environment without cage mates. RESULTS: Placing treats in the home cage shifted the cocaine dose-response curve to the left in five monkeys tested and to the right in 4 of 12 animals. The rubber snake significantly shifted the cocaine choice curve to the left in dominant monkeys. Exposure to an enlarged environment decreased cocaine choice in 9 of 15 monkeys; this effect was transient and not related to social rank. Repeated testing did not affect cocaine choice. CONCLUSIONS: Brief exposure to environmental events hypothesized to be stressors or enrichment altered cocaine choice, although not all individuals were affected and the effects were transient. Importantly, the data suggest that implementing positive changes in the environment produced effects that are clinically desirable. Understanding the behavioral and neurobiological mechanisms mediating sensitivity to environmental events in socially housed animals will lead to better treatment strategies for drug addiction. PMID- 22083592 TI - Anxiogenic-like effects of chronic cannabidiol administration in rats. AB - RATIONALE: Several pre-clinical and human-based studies have shown that acutely administered cannabidiol (CBD) can produce anxiolytic-like effects OBJECTIVES: The present study investigated the effects of chronic administration of CBD on rat behaviour and on the expression of brain proteins. METHODS: Male Lister hooded rats (150-200 g, n = 8 per group) received daily injections of CBD (10 mg/kg, i.p.) for 14 days. The rats were subjected to two behavioural tests: locomotor activity and conditioned emotional response (CER). The expression of brain-derived neurotrophic factor (BDNF), its receptor tyrosine kinase B (Trk B), extracellular signal-regulated kinases (ERK1/2) and phospho-ERK1/2 and the transcription factor cyclic AMP response element binding protein activation (CREB) and phospho-CREB were determined in brain regions such as the frontal cortex and hippocampus using Western immunoblotting. RESULTS: CBD significantly increased the time spent freezing in the CER test with no effect on locomotor activity. CBD significantly reduced BDNF expression in the hippocampus and frontal cortex with no change in the striatum. In addition, CBD significantly reduced TrkB expression in the hippocampus with a strong trend towards reduction in the striatum but had no effect in the frontal cortex. In the hippocampus, CBD had no effect on ERK1/2 or phospho-ERK2, but in the frontal cortex, CBD significantly reduced phospho-ERK1/2 expression without affecting total ERK. CONCLUSION: Chronic administration of CBD produced an anxiogenic-like effect in clear opposition to the acute anxiolytic profile previously reported. In addition, CBD decreased the expression of proteins that have been shown to be enhanced by chronic treatment with antidepressant/anxiolytic drugs. PMID- 22083593 TI - Trypanocidal activity of ergosterol peroxide from Pleurotus ostreatus. AB - Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi, is a public health problem in South America affecting millions of people, and more recently several thousands in countries where the disease is not endemic. Due to the magnitude of the problem, finding a cure for this disease remains a major challenge. The aim of this study is to evaluate the trypanocidal activity of ergosterol peroxide (5alpha, 8alpha-epidioxy-22E-ergosta-6, 22-dien-3beta-ol) isolated from Pleurotus ostreatus (Jacq.) P. Kumm. f. sp. Florida. The ergosterol peroxide showed strong trypanocidal activity on the intracellular form of T. cruzi. Ergosterol peroxide had an inhibitory concentration (IC50) of 6.74 ug/mL on T. cruzi, but showed no lytic action on erythrocytes and no cytotoxic effect on mammalian cells at concentrations higher than 1600 ug/mL. The interaction of Trypanosoma cruzi with ergosterol peroxide in vitro resulted in a strong lytic activity possibly due to the disruption of the parasite membrane. This is the first report of trypanocidal activity, a new biological property of ergosterol peroxide isolated from Pleurotus ostreatus (Jacq.) P. Kumm. f. sp. Florida. PMID- 22083594 TI - Local SAR in parallel transmission pulse design. AB - The management of local and global power deposition in human subjects (specific absorption rate, SAR) is a fundamental constraint to the application of parallel transmission (pTx) systems. Even though the pTx and single channel have to meet the same SAR requirements, the complex behavior of the spatial distribution of local SAR for transmission arrays poses problems that are not encountered in conventional single-channel systems and places additional requirements on pTx radio frequency pulse design. We propose a pTx pulse design method which builds on recent work to capture the spatial distribution of local SAR in numerical tissue models in a compressed parameterization in order to incorporate local SAR constraints within computation times that accommodate pTx pulse design during an in vivo magnetic resonance imaging scan. Additionally, the algorithm yields a protocol-specific ultimate peak in local SAR, which is shown to bound the achievable peak local SAR for a given excitation profile fidelity. The performance of the approach was demonstrated using a numerical human head model and a 7 Tesla eight-channel transmit array. The method reduced peak local 10 g SAR by 14-66% for slice-selective pTx excitations and 2D selective pTx excitations compared to a pTx pulse design constrained only by global SAR. The primary tradeoff incurred for reducing peak local SAR was an increase in global SAR, up to 34% for the evaluated examples, which is favorable in cases where local SAR constraints dominate the pulse applications. PMID- 22083595 TI - Extraction, identification and characterization of the water-insoluble proteins from tobacco biomass. AB - BACKGROUND: Tobacco leaves are a potential candidate for plant proteins, yielding fourfold more protein per acre than soybeans. However, more than 60% of these proteins are water-insoluble and remain in the residue (referred to as 'tobacco biomass') after aqueous extraction. Efficient extraction of tobacco biomass proteins (TBPs) could boost the development of value-added products from tobaccos. RESULTS: TBPs were resistant to salt extraction at pH 2.0-12.0, but they were readily extracted by organic solvents. A simplified extracting method, including mechanical homogenization, a first extraction with a methanol-water mixture (40/60, v/v) and a second one with water at pH 6.0, recovered at most 68% of the TBPs. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated the presence of both the water-soluble tobacco F(1) protein and the less soluble cell wall proteins in TBPs, while Fourier transform infrared spectra suggested the coexistence of TBPs with polysaccharides (especially pectin). Meanwhile, a higher content of hydrophobic amino acids was found in TBPs compared with water-extractable tobacco proteins. The amino acid score of TBPs was 0.71, with cysteine and methionine being the primary limiting amino acids. CONCLUSION: Satisfying recovery of TBPs was achieved using a two step organic solvent extraction. The hydrophobicity and protein-pectin interaction of TBPs explained for this result. PMID- 22083596 TI - Stool DNA testing for the detection of pancreatic cancer: assessment of methylation marker candidates. AB - BACKGROUND: Pancreatic cancer (PanC) presents at late stage with high mortality. Effective early detection methods are needed. Aberrantly methylated genes are unexplored as markers for noninvasive detection by stool testing. The authors aimed to select discriminant methylated genes and to assess accuracy of these and mutant KRAS in stool to detect PanC. METHODS: Nine target genes were assayed by real-time methylation-specific polymerase chain reaction (MSP) in bisulfite treated DNA from microdissected frozen specimens of 24 PanC cases and 30 normal colon controls. Archived stools from 58 PanC cases and 65 controls matched on sex, age, and smoking were analyzed. Target genes from fecal supernatants were enriched by hybrid capture, bisulfite-treated, and assayed by MSP. KRAS mutations were assayed using the QuARTS technique. RESULTS: Areas under the receiver operating characteristics curves (AUCs) for tissue BMP3, NDRG4, EYA4, UCHL1, MDFI, Vimentin, CNTNAP2, SFRP2, and TFPI2 were 0.90, 0.79, 0.78, 0.78, 0.77, 0.77, 0.69, 0.67, and 0.66, respectively. The top 4 markers and mutant KRAS were evaluated in stool. BMP3 was the most discriminant methylation marker in stool. At 90% specificity, methylated BMP3 alone detected 51% of PanCs, mutant KRAS detected 50%, and combination detected 67%. AUCs for methylated BMP3, mutant KRAS, and combination in stool were 0.73, 0.75, and 0.85, respectively. CONCLUSIONS: This study demonstrates that stool assay of a methylated gene marker can detect PanC. Among candidate methylated markers discriminant in tissue, BMP3 alone performed well in stool. Combining methylated BMP3 and mutant KRAS increased stool detection over either marker alone. PMID- 22083597 TI - Influences on blockade by t-butylbicyclo-phosphoro-thionate of GABA(A) receptor spontaneous gating, agonist activation and desensitization. AB - Picrotoxin and t-butylbicyclophosphorothionate (TBPS) are GABA(A) receptor (GABA(A)R) open channel blockers. However, picrotoxin displaceable [(35)S]TBPS binding to alpha1beta2gamma2 GABA(A)Rs occurs in the absence of GABA, suggesting that access to the binding site is independent of activation. Alternatively, spontaneous gating may provide access to the channel. In the absence of episodic GABA application, picrotoxin and TBPS blocked (by 91 +/- 3% and 85 +/- 5%, respectively) GABA-evoked currents mediated by alpha1beta2gamma2 receptors. We used two approaches to inhibit spontaneous GABA(A)R gating, bicuculline, which inhibits spontaneous current in the absence of exogenous agonist and the alpha1(K278M) mutant subunit. Whole-cell patch-clamp recordings demonstrated that alpha1(K278M)beta2gamma2 receptors have negligible spontaneous gating. Application of bicuculline to alpha1beta2gamma2 receptors in the absence of exogenous GABA caused a 35% reduction of current blockade by TBPS and reduced [(35)S]TBPS binding by 25%. Consistent with this, in the absence of exogenous GABA, alpha1(K278M)beta2gamma2 receptors exhibited reduced blockade by TBPS current compared to wild-type receptors. These data suggest that a decrease in spontaneous gating reduces accessibility of TBPS to its binding site. GABA application during picrotoxin or TBPS administration enhanced alpha1beta2gamma2 receptor blockade (to 98% in both cases). The GABA-dependent component of TBPS blockade accounts for the stimulation of [(35)S]TBPS binding to alpha1beta2gamma2 receptors seen with GABA (1 MUm) application. Moreover, application of GABA at concentrations that cause significant steady-state desensitization reduced [(35)S]TBPS binding. The alpha1(K278M) subunit slowed desensitization kinetics and increased the rate of deactivation of GABA-evoked currents. Furthermore, there was a marked increase in the GABA EC(50) for desensitization of alpha1(K278M)beta2gamma2 receptors associated with a large increase in the GABA dependent stimulation of [(35)S]TBPS binding. These data establish a relationship between GABA(A)R function and the three phases of [(35)S]TBPS binding seen in the absence and the presence of GABA. PMID- 22083598 TI - Phosphodiesterase 4 inhibition attenuates plasma volume loss and transvascular exchange in volume-expanded mice. AB - We tested the hypothesis that inhibition of phosphodiesterase 4 (PDE4) with rolipram to increase vascular endothelial cAMP and stabilize the endothelial barrier would attenuate the action of endogenous atrial natriuretic peptide (ANP) to increase vascular permeability to the plasma protein albumin after an acute plasma volume expansion. After rolipram pretreatment (8 mg (kg body wt)(-1), intraperitoneal, 30 min) more than 95% of the peak increase in plasma volume after volume expansion (4.5% bovine serum albumin, 114 MUl (g body wt)(-1) h(-1), 15 min) remained in the vascular space 75 min after the end of infusion, whereas only 67% of the fluid was retained in volume-expanded animals with no rolipram pretreatment. Rolipram significantly decreased 30 min fluorescently labelled albumin clearance (MUl (g dry wt)(-1)) relative to untreated volume-expanded controls in skin (e.g. back, 10.4 +/- 1.6 vs. 19.5 +/- 3.6, P = 0.04), muscle (e.g. hamstring, 15.0 +/- 1.9 vs. 20.8 +/- 1.4, P = 0.04) and in colon, caecum, and rectum (average reduction close to 50%). The mass of muscle and skin tissue accounted for 70% of volume-expansion-dependent albumin shifts from plasma to interstitium. The results are consistent with observations that the PDE4 inhibitor rolipram attenuates ANP-induced increases in vascular permeability after infusion of exogenous ANP and observations of elevated central venous pressure after a similar volume expansion in mice with selective deletion of the endothelial ANP receptor. These observations may form the basis for new strategies to retain intravenous fluid containing macromolecules. PMID- 22083599 TI - Intrinsic morphological diversity of thick-tufted layer 5 pyramidal neurons ensures robust and invariant properties of in silico synaptic connections. AB - The morphology of neocortical pyramidal neurons is not only highly characteristic but also displays an intrinsic diversity that renders each neuron morphologically unique. We investigated the significance of this intrinsic morphological diversity in in silico networks composed of thick-tufted layer 5 (TTL5) pyramidal neurons, by comparing the in silico and in vitro properties of TTL5 synaptic connections. The synaptic locations of in silico connections were determined by placing 3D reconstructed TTL5 neurons randomly in a volume equivalent to that of layer 5 in the juvenile rat somatosensory cortex and using a 'collision detection' algorithm to identify the incidental loci of axo-dendritic overlap. The activation time of the modelled synapses and their biophysical properties were characterized based on experimental measurements. We found that the anatomical loci of synapses and the physiological properties of the somatically recorded EPSPs closely matched those recorded experimentally without the need for any fine-tuning. Furthermore, perturbations to both the physiological or anatomical parameters of the model did not alter the average physiological properties of the population of modelled synaptic connections. This microcircuit level robust behaviour was due to the intrinsic diversity of the morphology of pyramidal neurons in the microcircuit. We conclude that synaptic transmission in a network of TTL5 neurons is highly invariant across microcircuits suggesting that intrinsic diversity is a mechanism to ensure the same average synaptic properties in different animals of the same species. Finally, we show that the average physiological properties of the TTL5 microcircuit are surprisingly robust to anatomical and physiological perturbations also partly due to the intrinsic diversity of pyramidal neuron morphology. PMID- 22083600 TI - Lobule-specific membrane excitability of cerebellar Purkinje cells. AB - Cerebellar Purkinje cells (PCs) are the sole output of the cerebellar cortex and function as key to a variety of learning-related behaviours by integrating multimodal afferent inputs. Intrinsic membrane excitability of neurons determines the input-output relationship, and therefore governs the functions of neural circuits. Cerebellar vermis consists of ten lobules (lobules I-X), and each lobule receives different sensory information. However, lobule-specific differences of electrophysiological properties of PC are incompletely understood. To address this question, we performed a systematic comparison of membrane properties of PCs from different lobules (lobules III-V vs. X). Two types of firing patterns (tonic firing and complex bursting) were identified in response to depolarizing current injections in lobule III-V PCs, whereas four distinct firing patterns (tonic firing, complex bursting, initial bursting and gap firing) were observed in lobule X. A-type K(+) current and early inactivation of fast Na(+) conductance with activation of 4-aminopyridine-sensitive conductances were shown to be responsible for the formation of gap firing and initial bursting patterns, respectively, which were observed only in lobule X. In response to current injection, PCs in lobule X spiked with wider dynamic range. These differences in firing pattern and membrane properties probably contribute to signal processing of afferent inputs in lobule-specific fashion, and particularly diversity of discharge patterns in lobule X, as a part of the vestibulocerebellum, might be involved in strict coordination of a precise temporal response to a wide range of head movements. PMID- 22083601 TI - Physiological characterization and functional heterogeneity of narrow-field mammalian amacrine cells. AB - Light-evoked responses of 106 morphologically identified narrow-field amacrine cells (ACs) were studied in dark-adapted mouse retinal slices. Forty-five cells exhibit AIIAC morphology, 55% of which show characteristic AIIAC physiological properties (AIIAC1s) and the remaining 45% display different physiological responses, suggesting that AIIACs are functionally heterogeneous. Moreover, we found that 42 cells exhibit morphology that resembles the seven morphological types of glycine-positive ACs (GlyAC1-7) reported in the rat retina, and for the first time assigned light response and function properties to these morphological types of glycinergic ACs in the mouse retina. In addition, five narrow-field ACs exhibited morphology resembling that of the GlyAC5 or GlyAC7 but with different physiological responses (GlyAC5(#) and GlyAC7(#)). Therefore, the eight morphological types of narrow-field ACs exhibit 12 classes of physiological responses. Furthermore, we found ACs whose physiological responses were indistinguishable from those of GlyAC3 or GlyAC4s but with different morphology (GlyAC3* or GlyAC4*). These observations suggest that although the majority of narrow-field mammalian ACs forms discrete functional groups that correlate with their morphology, a significant number of these cells with similar morphology do not display the same light responses, and some with similar light responses do not exhibit the same morphology. PMID- 22083602 TI - Chronic imaging of cortical sensory map dynamics using a genetically encoded calcium indicator. AB - In vivo optical imaging can reveal the dynamics of large-scale cortical activity, but methods for chronic recording are limited. Here we present a technique for long-term investigation of cortical map dynamics using wide-field ratiometric fluorescence imaging of the genetically encoded calcium indicator (GECI) Yellow Cameleon 3.60. We find that wide-field GECI signals report sensory-evoked activity in anaesthetized mouse somatosensory cortex with high sensitivity and spatiotemporal precision, and furthermore, can be measured repeatedly in separate imaging sessions over multiple weeks. This method opens new possibilities for the longitudinal study of stability and plasticity of cortical sensory representations. PMID- 22083603 TI - Postsynaptic BDNF signalling regulates long-term potentiation at thalamo-amygdala afferents. AB - The neurotrophin brain-derived neurotrophic factor (BDNF) is known to regulate synaptic plasticity and memory formation in the hippocampus and the neocortex of the mammalian brain. In contrast, a role of BDNF in mediating synaptic plasticity and fear learning in the amygdala is just beginning to evolve. Using patch clamp recordings from projection neurons of the dorsal lateral amygdala (LA) in acute slices of mice, we now investigated the cellular mechanism of BDNF-mediated long term potentiation (LTP) of excitatory postsynaptic currents (EPSCs) in the amygdala. LTP was elicited in cortical and thalamic synaptic inputs by pairing postsynaptic depolarisation with presynaptic stimulation. LTP in the cortico amygdala pathway was not changed in heterozygous BDNF-knockout (BDNF(+/-)) mice. In contrast, pairing induced LTP in the thalamic input was abolished in BDNF(+/-) mice (BDNF(+/-): 104.0 +/- 5.7% of initial EPSC values; WT: 132.5 +/- 7.3%). Likewise, inhibition of BDNF/TrkB signalling with TrkB-IgGs as scavenger molecules for endogenous BDNF blocked LTP in wild-type mice in this pathway (TrkB IgG: 102.7 +/- 6.9% of initial EPSC values; control: 132.5 +/- 8.7%). Inclusion of the tyrosine kinase inhibitor K252a in the pipette solution also prevented the induction of LTP in the thalamic pathway, indicating a postsynaptic site of action of BDNF in regulating LTP. Reduced BDNF levels in BDNF(+/-) mice did not affect intrinsic membrane properties of LA projection neurons. Likewise, presynaptic glutamate release, and postsynaptic membrane properties also remained unaffected in BDNF(+/-) mice. These data suggest a postsynaptic site of action of BDNF in mediating LTP selectively in the thalamic fear conditioning pathway. PMID- 22083604 TI - State of the art: surgery for endemic goiter. PMID- 22083605 TI - Inflammation and repeated infections in CGD: two sides of a coin. AB - Chronic granulomatous disease (CGD) is an uncommon congenital immunodeficiency seen approximately in 1 of 250,000 individuals. It is caused by a profound defect in a burst of oxygen consumption that normally accompanies phagocytosis in all myeloid cells (neutrophils, eosinophils, monocytes, and macrophages). This "respiratory burst" involves the catalytic conversion of molecular oxygen to the oxygen free-radical superoxide, which in turn gives rise to hydrogen peroxide, hypochlorous acid, and hydroxyl radicals. These oxygen derivatives play a critical role in the killing of pathogenic bacteria and fungi. As a result of the failure to activate the respiratory burst in their phagocytes, the majority of CGD patients suffer from severe recurrent infections and rather unexplained prolonged inflammatory reactions that may result in granulomatous lesions. Both may cause severe organ dysfunction depending on the tissues involved. Preventive measures as well as rapid (invasive) diagnostic procedures are required to successfully treat CGD. Hematopoietic stem cell transplantation may be a serious option in some of the patients. PMID- 22083607 TI - Rosai-Dorfman disease: presentation, diagnosis, and treatment. AB - BACKGROUND: Sinus histiocytosis with massive lymphadenopathy or Rosai-Dorfman disease (RDD) is a rare benign disease with nodal and extranodal involvement. METHODS AND RESULTS: Herein, we report 3 cases in which the patients presented with nasal masses. In addition, 2 of the 3 patients had subglottic lesions. Only 2 of the 3 patients had cervical lymphadenopathy, which is the commonest presentation of RDD. Histopathology via fine-needle aspiration cytology (FNAC) or open biopsy is required for diagnosis. Emperipolesis with S-100 immunohistochemical staining is characteristic. The disease runs a benign course and the literature reports that treatment can vary from steroids, to cytotoxic chemotherapy to radiotherapy with variable outcomes. Surgical intervention may be necessary for airway protection. CONCLUSION: RDD is self-limiting, but can sometimes be a life-threatening condition. Treatment should be tailored to the individual patient. PMID- 22083608 TI - 2,2'-Dithiobis(5-nitropyridine) (DTNP) as an effective and gentle deprotectant for common cysteine protecting groups. AB - Of all the commercially available amino acid derivatives for solid phase peptide synthesis, none has a greater abundance of side-chain protection diversity than cysteine. The high reactivity of the cysteine thiol necessitates its attenuation during peptide construction. Moreover, the propensity of cysteine residues within a peptide or protein sequence to form disulfide connectivity allows the opportunity for the peptide chemist to install these disulfides iteratively as a post-synthetic manipulation through the judicious placement of orthogonal pairs of cysteine S-protection within the peptide's architecture. It is important to continuously discover new vectors of deprotection for these different blocking protocols in order to achieve the highest degree of orthogonality between the removal of one species in the presence of another. We report here a complete investigation of the scope and limitations of the deprotective potential of 2,2' dithiobis(5-nitropyridine) (DTNP) on a selection of commercially available Cys S protecting groups. The gentle conditions of DTNP in a TFA solvent system show a remarkable ability to deprotect some cysteine blocking functionality traditionally removable only by more harsh or forcing conditions. Beyond illustrating the deprotective ability of this reagent cocktail within a cysteine containing peptide sequence, the utility of this method was further demonstrated through iterative disulfide formation in oxytocin and apamin test peptides. It is shown that this methodology has high potential as a stand-alone cysteine deprotection technique or in further manipulation of disulfide architecture within a more complex cysteine-containing peptide template. PMID- 22083609 TI - Histology of plastic embedded amphibian embryos and larvae. AB - Amphibians including the South African clawed frog Xenopus laevis, its close relative Xenopus tropicalis, and the Mexican axolotl (Ambystoma mexicanum) are important vertebrate models for cell biology, development, and regeneration. For the analysis of embryos and larva with altered gene expression in gain-of function or loss-of-function studies histology is increasingly important. Here, we discuss plastic or resin embedding of embryos as valuable alternatives to conventional paraffin embedding. For example, microwave-assisted tissue processing, combined with embedding in the glycol methacrylate Technovit 7100, is a fast, simple, and reliable method to obtain state-of-the-art histology with high resolution of cellular details in less than a day. Microwave-processed samples embedded in Epon 812 are also useful for transmission electron microscopy. Finally, Technovit-embedded samples are well suited for serial section analysis of embryos labeled either by whole-mount immunofluorescence, or with tracers such as GFP or fluorescent dextrans. Therefore, plastic embedding offers a versatile alternative to paraffin embedding for routine histology and immunocytochemistry of amphibian embryos. PMID- 22083606 TI - Eukaryotic DNA damage checkpoint activation in response to double-strand breaks. AB - Double-strand breaks (DSBs) are the most detrimental form of DNA damage. Failure to repair these cytotoxic lesions can result in genome rearrangements conducive to the development of many diseases, including cancer. The DNA damage response (DDR) ensures the rapid detection and repair of DSBs in order to maintain genome integrity. Central to the DDR are the DNA damage checkpoints. When activated by DNA damage, these sophisticated surveillance mechanisms induce transient cell cycle arrests, allowing sufficient time for DNA repair. Since the term "checkpoint" was coined over 20 years ago, our understanding of the molecular mechanisms governing the DNA damage checkpoint has advanced significantly. These pathways are highly conserved from yeast to humans. Thus, significant findings in yeast may be extrapolated to vertebrates, greatly facilitating the molecular dissection of these complex regulatory networks. This review focuses on the cellular response to DSBs in Saccharomyces cerevisiae, providing a comprehensive overview of how these signalling pathways function to orchestrate the cellular response to DNA damage and preserve genome stability in eukaryotic cells. PMID- 22083611 TI - Effect of methotrexate on inflammatory cells redistribution in experimental adjuvant arthritis. AB - The aim of this study was to evaluate the morphological changes in the spleen, the thymus and the knee joints of rats with experimental adjuvant arthritis induced by Mycobacterium butyricum in the incomplete Freund's adjuvant and the effect of treatment with methotrexate (MTX). Particular attention was aimed on the redistribution of granulocytes in the tissues during the inflammatory process. Clinical parameters, e.g., joint edema, body weight and of gamma glutamyl transferase (GGT) activity as an inflammatory marker, have also been determined. Induction of adjuvant arthritis caused a significant decrease in granulocyte number in the spleen and vice versa a significant increase in the knee joints, but without significant changes in the thymus. Treatment with methotrexate reversed this phenomenon by increasing the granulocyte number in the spleen and decreasing it in knee joints. MTX decreased the joint edema as well as the activity of GGT in the spleen, modified the size of the white pulp of the spleen and increased the cortex/medulla ratio in the thymus. The observed changes support the anti-inflammatory and immunomodulatory properties of MTX supporting its use as the first-line medication in patients with rheumatoid arthritis. PMID- 22083612 TI - Association study of the candidate gene for knee osteoarthritis in Koreans. AB - The aim of this study was to examine a single-nucleotide polymorphism (SNP) rs7639618 of double von Willebrand factor (DVWA) gene for the association with osteoarthritis (OA) susceptibility in Korean cohort. The study was a part of the Korean cohort study. Two thousand four hundred sixty-two subjects aged 50 years and older who were derived from the cohort and who were assessed for OA at the knee were genotyped. The anteroposterior extended-view weight-bearing radiographs of the knees were obtained. Of the subjects, 725 subjects had radiographic OA. Genomic DNA was extracted from peripheral blood using a QIAamp DNA Blood Mini Kit (Qiagen, Valencia, CA). Genotyping was performed using High Resolution Melt or the Taq-Man allelic discrimination assay and the Rotor-Gene 6000 (Corbett Research, Sydney,Australia). Associations were tested by calculating the odds ratios (ORs) and 95% confidence intervals (95% CIs), using logistic regression analysis with adjustments for age, gender, and body mass index (BMI). The mean age of the OA patients (females: 554 subjects, 76.4%) was 67.4 (7.9) years. The intraobserver agreement was high for the identification of osteophytes (kappa: 0.80) and joint space narrowing (kappa: 0.70). There was no significant difference (all P values > 0.05) in the genotype or allele frequencies between the patients with OA and healthy controls. There was also no significant difference when the cases were adjusted by age, gender, and BMI. The associations of DVWA SNPs with OA were noted in previous studies and were not found in the Korean OA cohort. PMID- 22083610 TI - Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. AB - Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented. PMID- 22083613 TI - Differential proteomic analysis of renal tissue in lupus nephritis using iTRAQ reagent technology. AB - In clinical practice, it is difficult to monitor the repeating relapse in patients suffering from systemic lupus erythematosus (SLE), who usually associated with some potential complications, for example, lupus nephritis (LN), repetition renal biopsy is necessary to determine LN flares. To identify and quantify the total proteins in renal tissue of LN patients, isobaric tags for relative and absolute quantification (iTRAQ) technology was performed. Eight-plex iTRAQ coupled with multiple chromatographic fractionation and tandem mass spectrometry were used to analyze total proteins in renal tissue of LN patients and healthy controls. Proteins were identified by mascot, which expressed differentially were noted. A total of 490 distinct proteins were identified, 113 proteins were up-regulation or down-regulation at one fold or more alteration in levels. Among of them, there was significant deviation of four proteins between our present iTRAQ study, which are up-regulated heterogeneous nuclear ribonucleoprotein (hnRNP-), Annexins and down-regulated Argininosuccinate synthetase (ASS), aldolase. iTRAQ-based quantitative proteomic technology is efficiently applicable for identification and relative quantitation of proteome of renal tissue. Differentially expressed proteome profiles of LN patients are determined. And further investigation is necessary using large cohorts of patient samples with long-term clinical follow-up data, to assess the usefulness of the pathogenesis and novel biomarker candidates of LN, which may develop a new way for diagnosis of LN. PMID- 22083614 TI - Bamboo nodes associated with mixed connective tissue disease as a cause of hoarseness. AB - Vocal fold lesions related to autoimmune diseases are rheumatoid nodules and, to a lesser extent, bamboo nodes. Mostly transverse, they are located in the middle third of the vocal cord and exhibit a yellowish appearance. The characteristic shape of these lesions led to their name. These vocal fold deposits may interfere with the normal vibratory cycle during phonation and thus may be an unusual cause of hoarseness. We present a 43-year-old woman with known mixed connective tissue disease and a dysphonia. Laryngostroboscopy showed bamboo nodes as described above. We applied several laryngeal injections of cortisone as described previously in the literature. Since this treatment did not lead to a sufficient voice improvement, we attempted to surgically remove the deposits. After the surgery, the voice improved considerably. In all patients with rheumatic diseases who suffer from a rough, breathy, or unstable voice, a laryngostroboscopic examination should be done. If, however, a bamboo node lesion of the vocal folds is found by the laryngologists, an associated autoimmune disorder must be assumed, and adequate diagnostic procedures have to be initiated. Local laryngeal injections (1-3 times) with steroids should be the first line of therapy. In unsuccessful cases, subsequent surgery can be a useful treatment of bamboo nodes to stabilize and improve voice quality. PMID- 22083615 TI - The prevalence and progression of radiographic knee osteoarthritis over 6 years in a population-based cohort of middle-aged subjects. AB - Details of the development of early knee osteoarthritis (OA) are largely unknown. The prevalence and progression of radiographic knee OA over 6 years in middle aged subjects with chronic knee pain is investigated. In a prospective population based study, tibiofemoral (TF) and patellofemoral (PF) radiographs were graded in 128 subjects (mean age 45 +/- 6.2 years) for the presence of osteophytes and joint space narrowing (JSN). Radiographic progression was defined as: (i) the presence of osteophytes and/or JSN in subjects with no previous OA or (ii) an increase in the grade and/or number of already existing osteophytes and/or JSN. Altogether 56% (72/128) of subjects had knee OA, the majority of them was diagnosed with OA grade 1. In 57% of cases, radiographic OA was based on the presence of osteophytes alone versus 13% on JSN. More than 1/3 of subjects had isolated PF joint involvement. Knee OA progression rate over 6 years was 56% (71/128). During 6 years, a non-linear course of radiographic OA progression with intermittent periods of progression and stabilization was observed. Individual course of OA revealed distinct subsets of radiographic progression. Osteophytosis is an important early radiographic sign of OA and its progression. Isolated PF joint involvement is a frequent expression of knee OA. In middle-aged subjects, the progression rate of knee OA over 6 years was 56%. A non-linear course of radiographic OA progression was observed. Several radiographic subsets refer to the heterogeneity of the OA process. PMID- 22083616 TI - Anti-cyclic citrullinated peptide antibodies and rheumatoid factor sera titers in leprosy patients from Mexico. AB - Leprosy offers a broad spectrum of altered immunological sceneries, ranging from strong cell-mediated immune responses seen in tuberculoid leprosy (TT), through borderline leprosy (BB), to the virtual absence of T cell responses characteristic in lepromatous leprosy (LL). The exact mechanism of autoantibodies production remains unknown in leprosy and other chronic inflammatory diseases and also the contribution of these antibodies to the pathogenesis of the disease. The aim of this study is to evaluate the frequency and profiles of serum anti-cyclic citrullinated peptide antibodies (a-CCP), rheumatoid factor (RF) and its relationship with leprosy spectrum. Serum samples from 67 leprosy patients (54 LL, 5 TT and 8 BB) and 46 clinically healthy subjects (CHS) from the same endemic region were investigated. The clinical chart and questionnaire were used to obtain clinical information. Anti-cyclic citrullinated peptide antibodies (a-CCP) were measured by enzyme-linked immunosorbent assay, whereas the rheumatoid factor (RF) levels were measured by nephelometric method. The mean age of patients was 51.5 +/- 13 years. Sera levels of a-CCP where higher in leprosy patients than in CHS (5.9 +/- 11.6 vs. 0.3 +/- 0.29) (P < 0.0001); the same pattern was found for RF sera titers without reaching statistical significance (16.8 +/- 22.5 vs. 9.9 +/- 3) (P = NS). We did not find a correlation between a-CCP and RF Rho =0.02786 (IC 95%) P = 0.8229. However, LL patients had higher a-CCP and RF levels than TT patients. Although an absence in correlation was observed, the serum levels of a CCP antibodies and RF appeared to be useful in distinguishing LL from TT patients with a limited significance in detecting reactional leprosy patients. PMID- 22083617 TI - Synovial fluid and serum levels of IL-17, IL-23, and CCL-20 in rheumatoid arthritis and psoriatic arthritis: a Tunisian cross-sectional study. PMID- 22083619 TI - Anakinra: a safe and effective first-line treatment in systemic onset juvenile idiopathic arthritis (SoJIA). AB - Systemic onset juvenile idiopathic arthritis (SoJIA) is a rare inflammatory disorder. It can result in disease and treatment-related disability. SoJIA is characterized by remitting fevers, evanescent rash, generalized lymphadenopathy, hepatomegaly/splenomegaly, and/or serositis. Non-responsiveness to standard therapy with corticosteroids and disease modifying antirheumatic drugs is not uncommon. IL-1beta has been shown to be a main contributor to the pathogenesis of SoJIA. Anakinra, a recombinant IL-1beta receptor antagonist, was shown to be effective in small cohorts of therapy-resistant adult and pediatric Still's patients. In order to assess the efficacy and safety of first-line anakinra treatment in SoJIA, we reviewed the charts of all SoJIA patients in our institution from 2005 to 2010, searching for first-line anakinra-treated patients. We report the clinical and laboratory course of four SoJIA patients. The mean follow-up was 13.5 (range: 2-50) months. Anakinra was started at doses from 1.5 to 4 mg/kg for a median duration of 3 (range: 3-18) months. Two patients responded to anakinra mono-therapy; two cases required corticosteroids. Normalized body temperatures and the absence of evanescent rashes were achieved after a median of 4 (range: 2-10) days. We did not see treatment-related adverse reactions other than local injection site inflammation. This is the first single center series, reporting anakinra as first-line treatment in SoJIA. We show rapid efficacy of anakinra in early SoJIA with reduced treatment-related side effects. A subset of patients remains corticosteroid dependent. Further studies are warranted to follow larger cohorts and to assess long-term safety. PMID- 22083618 TI - Anomalies of intra-synovial citrullination: is there any interest in the diagnosis of early rheumatoid arthritis? AB - Autoantibodies to citrullinated proteins (ACPA) are specifically associated with rheumatoid arthritis (RA) and seem to play an important role in its pathogenesis. The specific immunological conflict between ACPA and citrullinated fibrin plays a major role in the self-maintenance of synovial inflammation by forming fibrin deposits in the synovial tissue. These deposits, secondarily citrullinated by a local peptidylarginine deiminase (PADI) enzyme activity, seem to maintain the immunological conflict and the inflammation. Our objective in this work is to study the anomalies of citrullination in a group of patients with early RA, in comparison with a control group of patients suffering from undetermined inflammatory arthritis, osteoarthritis and spondyloarthropathy. For this purpose, we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of ACPA in serum and synovial fluid. By immunohistochemistry, subtype 4 of PADI was also sought in the synovial biopsies taken from all our patients. We found that the ACPA levels in serum and synovial fluid were significantly higher in patients with RA. The enzyme PADI4 was found only in the group with RA and was statistically correlated with ACPA mean levels in sera and synovial fluid. The expression of PADI4 seems to correlate with intra-synovial deposits of fibrin in RA. However, determination of synovial ACPA levels and detection of intra synovial PADI4 deposits are of no additional benefit compared with assessment of ACPA levels in serum for the diagnosis of early RA. PMID- 22083620 TI - An unusual cause of hemichorea-hemiballism in a patient with systemic lupus erythematosus. PMID- 22083621 TI - Meeting report: novel targets for cancer and connective tissues diseases. PMID- 22083622 TI - Comparison of single-port laparoscopy, standard laparoscopy, and robotic surgery in patients with endometrial cancer. AB - BACKGROUND: The aim of this study was to evaluate single-port laparoscopy (SPL) for the surgical treatment of presumed early-stage endometrial cancer and to compare surgical outcomes to laparoscopy and robotics. METHODS: A multi institutional, matched retrospective cohort study was performed. All patients with clinical stage I or occult stage II endometrial cancer who underwent SPL hysterectomy, bilateral salpingo-oophorectomy +/- lymphadenectomy from April 2009 to September 2010 were identified. Outcomes were compared with patients matched by age, body mass index (BMI), tumor histology, and grade, who underwent laparoscopy or robotic surgery. Data was analyzed using Kruskal-Wallis 1-way analysis of variance and chi-square test for frequency data. A P value of <.05 was considered significant. RESULTS: A total of 90 matched patients (30 SPL, 30 LSC, and 30 robotic) were included in the study. There were no significant differences in median operating time or estimated blood loss between the 3 groups. The median number of pelvic lymph nodes obtained was significantly higher in the robotic (17.0 [8-36] and SPL group (16.0 [11-21]) compared with the laparoscopy group (13.0 [3-18]) P = .04. However, there was no significant difference in the median number of para-aortic nodes obtained between the 3 groups. There was no significant difference between the groups in length of hospital stay, comorbid conditions, complication rates, or operative times. CONCLUSIONS: Our findings suggest SPL surgery for endometrial carcinoma is feasible with similar operating times, hospital length of stay, complication rates, and estimated blood loss when compared with laparoscopy and robotics. PMID- 22083623 TI - Determination of quinine in beverages by online coupling capillary isotachophoresis to capillary zone electrophoresis with UV spectrophotometric detection. AB - The present study illustrates the possibilities of capillary isotachophoresis (CITP) online coupled with capillary zone electrophoresis (CZE) and hyphenated with fiber-based spectrophotometric diode array detection (DAD) for the direct, highly reliable, and ultrasensitive determination of quinine (QUI) in real multicomponent ionic matrices (beverages). Here, the CITP provided an effective online sample pretreatment (preseparation and preconcentration) prior to the CZE separation. Due to the CITP sample preconcentration, a simple UV-visible absorbance spectrophotometric detection was sufficient for obtaining very low concentration limits of detection (~2.3 ng/mL). Enhanced separation selectivity due to the combination of different separation mechanisms (CITP vs. CZE) enabled to obtain a pure analyte zone, suitable for its detection and quantitation in the directly injected real samples. The spectrophotometric DAD, unlike single wavelength UV detection, enabled to characterize the purity (i.e. spectral homogeneity) of the analyte zone and preliminary data indicate structurally related compounds via characteristic spectra recorded in the interval of 200-600 nm. The proposed CITP-CZE-DAD method was characterized by favorable performance parameters (sensitivity, linearity, precision, recovery, accuracy, robustness, and selectivity) and successfully applied to the control of QUI and potential QUI impurities in commercial beverages. This method is proposed as a routine automatized method for the highly reliable quality food control. PMID- 22083624 TI - Stable transformation and cloning mediated by piggyBac vector and RNA interference knockdown of Drosophila ovarian cell line. AB - An in vitro study is a powerful method for elucidating gene functions in cellular and developmental events. However, until date, no reliable in vitro transformation, cloning, or knockdown system has been reported for Drosophila cells, with the exception of S2 and Kc cells. In this study, we demonstrated that the piggyBac vector stably integrates donor DNA into ovarian somatic sheets derived from follicle stem cells. The transformed ovarian somatic sheet cells were easily cloned with a new piggyBac selection vector carrying enhanced green fluorescent protein and dihydrofolate reductase genes, egfp, and dhfr, respectively, in culture media containing methotrexate, an inhibitor of DNA synthesis. Donor egfp continued to be expressed at a high level in long-term culture. Furthermore, the translation of donor egfp was inhibited by treatment with double-stranded RNA derived from the target gene. The transfection and cloning methods mediated by the piggyBac vector would thus be useful for future analyses of gene functions in OSS cells and possibly be applicable to other Drosophila cell lines. PMID- 22083625 TI - Antioxidant effect of a phytoestrogen equol on cultured muscle cells of embryonic broilers. AB - Previous studies have shown that the in ovo injection of equol can markedly improve the water-holding capacity of muscles of broilers chickens at 7 wk of age through promotion of the antioxidant status. We aimed to investigate directly the antioxidant effects of equol on muscle cells in broilers. Muscle cells were separated from leg muscle of embryos on the 11th day of incubation and treated with equol and H(2)O(2), either alone or together. Cells were pretreated with medium containing 1, 10, or 100 MUM equol for 1 h prior to the addition of 1 mM H(2)O(2) for a further 1 h. Photomicrographs of cells were obtained. Cell viability, malondialdehyde (MDA) content, and L-lactate dehydrogenase (LDH) activity in the cell supernatant, as well as intracellular total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities were determined. Treatment with 1 mM H(2)O(2) caused serious damage to cells, indicated by comets with no clear head region but a very apparent tail of DNA fragments. Pretreatment with low (1 MUM) but not high concentrations of equol (10 MUM) inhibited cell damage, while 100 MUM equol caused more serious damage than H(2)O(2) alone. Pretreatment with 1 MUM equol had no effect on cell viability, while pretreatment with 10 and 100 MUM equol significantly decreased cell viability in a dose dependent manner. Compared with H(2)O(2) alone, pretreatment with low-dosage equol markedly decreased LDH activity and MDA production in the supernatant, significantly increased intracellular T-SOD activity (P < 0.05) and tended to increase intracellular GSH-Px activity (0.05 < P < 0.1). Pretreatment with high dosage equol (10 and 100 MUM) significantly enhanced LDH activity, but had no effect on MDA content, T-SOD or GSH-Px activity induced by H(2)O(2,) except for an obvious increase in GSH-Px activity caused by 10 MUM equol. These results indicate that equol at low dosage can prevent skeletal muscle cell damage induced by H(2)O(2), while pretreatment with high-dosage equol shows a synergistic effect with H(2)O(2) in inducing cell damage. PMID- 22083626 TI - Study strategies of college students: are self-testing and scheduling related to achievement? AB - Previous studies, such as those by Kornell and Bjork (Psychonomic Bulletin & Review, 14:219-224, 2007) and Karpicke, Butler, and Roediger (Memory, 17:471-479, 2009), have surveyed college students' use of various study strategies, including self-testing and rereading. These studies have documented that some students do use self-testing (but largely for monitoring memory) and rereading, but the researchers did not assess whether individual differences in strategy use were related to student achievement. Thus, we surveyed 324 undergraduates about their study habits as well as their college grade point average (GPA). Importantly, the survey included questions about self-testing, scheduling one's study, and a checklist of strategies commonly used by students or recommended by cognitive research. Use of self-testing and rereading were both positively associated with GPA. Scheduling of study time was also an important factor: Low performers were more likely to engage in late-night studying than were high performers; massing (vs. spacing) of study was associated with the use of fewer study strategies overall; and all students-but especially low performers-were driven by impending deadlines. Thus, self-testing, rereading, and scheduling of study play important roles in real-world student achievement. PMID- 22083628 TI - Changing careers in chemistry. PMID- 22083627 TI - Active and passive contributions to spatial learning. AB - It seems intuitively obvious that active exploration of a new environment will lead to better spatial learning than will passive exposure. However, the literature on this issue is decidedly mixed-in part, because the concept itself is not well defined. We identify five potential components of active spatial learning and review the evidence regarding their role in the acquisition of landmark, route, and survey knowledge. We find that (1) idiothetic information in walking contributes to metric survey knowledge, (2) there is little evidence as yet that decision making during exploration contributes to route or survey knowledge, (3) attention to place-action associations and relevant spatial relations contributes to route and survey knowledge, although landmarks and boundaries appear to be learned without effort, (4) route and survey information are differentially encoded in subunits of working memory, and (5) there is preliminary evidence that mental manipulation of such properties facilitates spatial learning. Idiothetic information appears to be necessary to reveal the influence of attention and, possibly, decision making in survey learning, which may explain the mixed results in desktop virtual reality. Thus, there is indeed an active advantage in spatial learning, which manifests itself in the task dependent acquisition of route and survey knowledge. PMID- 22083629 TI - Growth hormone secretagogues: out of competition. AB - Growth hormone secretagogues (GHS) constitute a new GH deficiency treatment increasing exponentially in number and improved potency and bioavailability over the last decade. The growth hormone releasing activity makes these compounds attractive for the artificial improvement of the human sports skills, now that recombinant human growth hormone (rhGH) administration is effectively detected. The GHS family is extremely diverse both in number and chemical heterogeneity and keeps growing continuously. In this paper, a general screening test is proposed. To develop a universal method, the single common property of growth hormone secretagogues has been targeted: their capacity to bind to the GHS receptor 1a (GHS-R1a). Pretreated urine samples have been tested in a competition assay where eventually the GHS presence detached a radiolabelled ligand from the receptor in a dose-dependent manner. Blank urine samples were processed to determine potential age, gender and exercise effects, and to define a threshold beyond which a specimen is considered positive. Samples from a growth hormone releasing peptide 2 (GHRP-2) excretion study corroborated the screening assay applicability with a detection window of approximately 4.5 h, and results were confirmed by comparison with a dedicated LC-MS quantification of the intact compound. PMID- 22083630 TI - A novel off-center paddle impeller (OPI) dissolution testing system for reproducible dissolution testing of solid dosage forms. AB - Dissolution testing is routinely conducted in the pharmaceutical industry to provide in vitro drug release information for quality control purposes. The most common dissolution testing system for solid dosage forms is the United States Pharmacopeia (USP) Dissolution Testing Apparatus 2. This apparatus is very sensitive to the initial location of the tablet, which cannot be controlled because the tablet is dropped into the vessel at the beginning of the test and it may rest at random locations at the vessel's bottom. In this work, a modified Apparatus 2 in which the impeller was placed 8 mm off center in the vessel was designed and tested. This new design was termed "OPI" for "off-center paddle impeller." Dissolution tests were conducted with the OPI apparatus for nine different tablet locations using both disintegrating tablets (prednisone) and nondisintegrating tablets (salicylic acid). The dissolution profiles in the OPI apparatus were largely independent of the tablet location at the vessel's bottom, whereas those obtained in the Standard System generated statistically different profiles depending on the tablet location. The newly proposed OPI system can effectively eliminate artifacts generated by random settling of the tablet at the vessel's bottom, thus making the test more robust. PMID- 22083631 TI - Magnesium nutrition on accumulation and transport of amino acids in tea plants. AB - BACKGROUND: Free amino acids in young tea shoots are important chemical constituents, remarkably influencing the quality of green teas. Nutrient solution, soil pot and field experiments were conducted to investigate the effect of magnesium nutritional status on accumulation and transport of free amino acids in tea plants (Camellia sinensis (L.) O. Kuntze). RESULTS: A sufficient supply of Mg in nutrient solution increased biomass production and concentrations of free amino acids, notably theanine in young shoots and roots, without affecting total N in the leaves, absorption rates of inorganic N and glutamine synthetase activity. Amino acids in xylem saps and phloem exudates or total sugars in phloem exudates of tea plants from pot and field experiments showed their highest levels in bud breaking and shoot extension in early spring (March and early April). Application of Mg increased the amounts of amino acids and total sugars in the xylem saps and phloem exudates. CONCLUSION: Adequate supply of Mg nutrient promoted the synthesis of theanine in roots and its accumulation in the young shoots of tea plants. Magnesium nutritional status was an important factor influencing the mobility of amino acids and sugars via xylem and phloem especially when N and C reserves remobilized to support spring growth of young shoots. PMID- 22083634 TI - PPAR-alpha targeting in kidney fibrosis: is BAY PP1 just another renoprotector? AB - Interstitial fibrosis plays a major role in the progression of renal diseases. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) ligands are increasingly explored for their potential to reverse or halt tubulointerstitial fibrosis. This Commentary discusses new findings by Boor et al., who show that BAY PP1, a novel PPAR-alpha agonist, ameliorates renal fibrosis and dysfunction. PMID- 22083635 TI - Old friends form alliance against podocytes. AB - Wang and colleagues identify the activation of Wnt signaling as an important downstream event in transforming growth factor-beta-mediated podocyte injury. Supported by other recent studies, canonical Wnt signaling is emerging as a critical stress pathway in podocytes and may be exploited for therapeutic strategies in the treatment of glomerulopathies. PMID- 22083636 TI - Blockade of PDGF receptor signaling reduces myofibroblast number and attenuates renal fibrosis. AB - Fibrosis can be considered as wound healing that never ceases, and activated fibroblasts (myofibroblasts) probably play a critical role in this unabated tissue repair process. In the setting of renal fibrosis, two central questions remain unanswered: Where do activated myofibroblasts come from; and what mechanism or mechanisms keep them activated? The study by Chen and colleagues addresses the role of platelet-derived growth factor receptor (PDGFR) signaling in the activation of myofibroblasts. PMID- 22083637 TI - Warfarin-related nephropathy can be mimicked by an interaction between sulfonamide derivatives and vitamin K antagonists. PMID- 22083638 TI - Dental caries in renal tubular acidosis. PMID- 22083639 TI - Multiplexed immunoassay of thyroglobulin autoantibodies in patients with differentiated thyroid carcinoma. AB - BACKGROUND: Thyroglobulin (Tg) antibodies (TgAb) screening is recommended in patients with differentiated thyroid carcinoma (DTC) to validate Tg measurements. We compared a new multiplexed and 2 conventional TgAb immunoassays in patients with DTC and healthy controls. METHODS: TgAb were measured by 2 conventional automated immunoassays and a multiplexed immunoassay in sera from 163 patients with DTC and 64 controls. RESULTS: No significant differences were found between the different assays when the suggested manufacturer cutoffs were used. The positive rate of multiplexed assay, but not of conventional assays, significantly increased when limits of detection were used as cutoff. CONCLUSION: Further technical evaluations are necessary to explain the very high rate of detectable TgAb values in both patients with DTC and controls by the multiplexed assay. For the moment, we suggest caution in using such methods in the current clinical practice. PMID- 22083640 TI - The ventriculophasic response revisited: analysis of clinical correlations using a new proposed definition derived in pacemaker patients. AB - BACKGROUND: The ventriculophasic response (VR) refers to shortening of atrial cycle length during heart block when a QRS complex is interposed between P waves. No formal quantitative definition has heretofore been proposed, nor have its potential clinical correlations been studied. HYPOTHESIS: We hypothesized that VR is present in selected patients who are distinguished by clinical features from those who lack VR. METHODS: Pacing devices were temporarily programmed to VVI mode at 30 ppm as electrocardiogram and intracardiac electrograms were recorded at 50 mm/sec paper speed. We measured the percentage decrease in a P-P interval (A-A interval on the atrial electrogram) containing a QRS, compared to the preceding P-P interval. Left ventricular ejection fraction (LVEF) was measured by echocardiogram. RESULTS: Shortening of P-P interval was observed chiefly when the interposed QRS occurred early in the anticipated P-P interval (as judged by the preceding P-P interval). P-P shortening of 0% to 3% occurred randomly. Defining VR as being a >3% P-P interval shortening when an interposed QRS occurred in the first 60% of the anticipated P-P interval, we found that VR was present in 28 (55%) of our patients. It was quite reproducible, was more common in women (81% vs 37% of men; P = 0.004), and positively correlated with LVEF (r = 0.41, P = 0.004). It did not correlate with age, diabetes, or beta-blocker use. CONCLUSIONS: Using our newly derived definition of VR, we found the phenomenon was present in 55% of our patients. It was reproducible and more commonly seen in women and patients with LVEF >=40%. PMID- 22083641 TI - ClC-5 mutations associated with Dent's disease: a major role of the dimer interface. AB - Dent's disease is an X-linked recessive disorder affecting the proximal tubules. Mutations in the 2Cl(-)/H(+) exchanger ClC-5 gene CLCN5 are frequently associated with Dent's disease. Functional characterization of mutations of CLCN5 have helped to elucidate the physiopathology of Dent's disease and provided evidence that several different mechanisms underlie the ClC-5 dysfunction in Dent's disease. Modeling studies indicate that many CLCN5 mutations are located at the interface between the monomers of ClC-5, demonstrating that this protein region plays an important role in Dent's disease. On the basis of functional data, CLCN5 mutations can be divided into three different classes. Class 1 mutations impair processing and folding, and as a result, the ClC-5 mutants are retained within the endoplasmic reticulum and targeted for degradation by quality control mechanisms. Class 2 mutations induce a delay in protein processing and reduce the stability of ClC-5. As a consequence, the cell surface expression and currents of the ClC-5 mutants are lower. Class 3 mutations do not alter the trafficking of ClC-5 to the cell surface and early endosomes but induce altered electrical activity. Here, we discuss the functional consequences of the three classes of CLCN5 mutations on ClC-5 structure and function. PMID- 22083642 TI - Brainstem mechanisms of paradoxical (REM) sleep generation. AB - Paradoxical sleep (PS) is characterized by EEG activation with a disappearance of muscle tone and the occurrence of rapid eye movements (REM) in contrast to slow wave sleep (SWS, also known as non-REM sleep) identified by the presence of delta waves. Soon after the discovery of PS, it was demonstrated that the structures necessary and sufficient for its genesis are restricted to the brainstem. We review here recent results indicating that brainstem glutamatergic and GABAergic, rather than cholinergic and monoaminergic, neurons play a key role in the genesis of PS. We hypothesize that the entrance to PS from SWS is due to the activation of PS-on glutamatergic neurons localized in the pontine sublaterodorsal tegmental nucleus. The activation of these neurons would be due to a permanent glutamatergic input arising from the lateral and ventrolateral periaqueductal gray (vlPAG) and the removal at the onset of PS of a GABAergic inhibition present during W and SWS. Such inhibition would be coming from PS-off GABAergic neurons localized in the vlPAG and the adjacent deep mesencephalic reticular nucleus. The cessation of activity of these PS-off GABAergic neurons at the onset and during PS would be due to direct projections from intermingled GABAergic PS-on neurons. Activation of PS would depend on the reciprocal interactions between the GABAergic PS-on and PS-off neurons, intrinsic cellular and molecular events, and integration of multiple physiological parameters. PMID- 22083643 TI - Mechanisms of sleep-disordered breathing: causes and consequences. AB - Obstructive sleep apnea (OSA) is very common in the general population and is characterized by ineffective inspiratory efforts against a collapsed upper airway during sleep. Collapse occurs mainly at the level of the velopharynx and oropharynx due to a combination of predisposing anatomy and the withdrawal of pharyngeal dilator activity during sleep. Central sleep apnea (CSA) is a manifestation of chemoreflex control instability, leading to periods of inadequate respiratory drive sufficient to trigger breathing, usually alternating with periods of hyperventilation. While both forms of apnea are the result of differing pathophysiology, it has become increasingly clear that OSA and CSA often coexist in the same patient, the existence of one can predispose to the other, and that the two are not as distinct as previously thought. Both OSA and CSA exert a number of acute deleterious effects including intermittent hypoxia, arousals from sleep, and swings in negative intrathoracic pressure, which in turn lead to chronic physiologic consequences such as autonomic dysregulation, endothelial dysfunction, and cardiac remodeling. These underlying pathophysiological mechanisms provide a framework for understanding why OSA and CSA may predispose to cardiovascular diseases like ischemic heart disease and stroke. PMID- 22083645 TI - In vivo three-dimensional whole-brain pulsed steady-state chemical exchange saturation transfer at 7 T. AB - Chemical exchange saturation transfer (CEST) is a technique to indirectly detect pools of exchangeable protons through the water signal. To increase its applicability to human studies, it is needed to develop sensitive pulse sequences for rapidly acquiring whole-organ images while adhering to stringent amplifier duty cycle limitations and specific absorption rate restrictions. In addition, the interfering effects of direct water saturation and conventional magnetization transfer contrast complicate CEST quantification and need to be reduced as much as possible. It is shown that for protons exchanging with rates of less than 50 100 Hz, such as imaged in amide proton transfer experiments, these problems can be addressed by using a three-dimensional steady state pulsed acquisition of limited B(1) strength (~ 1 MUT). Such an approach exploits the fact that the direct water saturation width, magnetization transfer contrast magnitude, and specific absorption rate increase strongly with B(1) , while the size of the CEST effect for such protons depends minimally on B(1) . A short repetition time (65 ms) steady-state sequence consisting of a brief saturation pulse (25 ms) and a segmented echo-planar imaging train allowed acquisition of a three-dimensional whole-brain volume in approximately 11 s per saturation frequency, while remaining well within specific absorption rate and duty cycle limits. Magnetization transfer contrast was strongly reduced, but substantial saturation effects were found at frequencies upfield from water, which still confound the use of magnetization transfer asymmetry analysis. Fortunately, the limited width of the direct water saturation signal could be exploited to fit it with a Lorentzian function allowing CEST quantification. Amide proton transfer effects ranged between 1.5% and 2.5% in selected white and grey matter regions. This power and time-efficient 3D pulsed CEST acquisition scheme should aid endogenous CEST quantification at both high and low fields. PMID- 22083646 TI - Interference of low-molecular substances with the thioflavin-T fluorescence assay of amyloid fibrils. AB - Abnormal fibrillization of amyloidogenic peptides/proteins has been linked to various neurodegenerative diseases such as Alzheimer's and Parkinson's disease as well as with type-II diabetes mellitus. The kinetics of protein fibrillization is commonly studied by using a fluorescent dye Thioflavin T (ThT) that binds to protein fibrils and exerts increased fluorescence intensity in bound state. Recently, it has been demonstrated that several low-molecular weight compounds like Basic Blue 41, Basic Blue 12, Azure C, and Tannic acid interfere with the fluorescence of ThT bound to Alzheimers' amyloid-beta fibrils and cause false positive results during the screening of fibrillization inhibitors. In the current study, we demonstrated that the same selected substances also decrease the fluorescence signal of ThT bound to insulin fibrils already at submicromolar or micromolar concentrations. Kinetic experiments show that unlike to true inhibitors, these compounds did neither decrease the fibrillization rate nor increase the lag-period. Absence of soluble insulin in the end of the experiment confirmed that these compounds do not disaggregate the insulin fibrils and, thus, are not fibrillization inhibitors at concentrations studied. Our results show that interference with ThT test is a general phenomenon and more attention has to be paid to interpretation of kinetic results of protein fibrillization obtained by using fluorescent dyes. PMID- 22083644 TI - Identification of the muscarinic pathway underlying cessation of sleep-related burst activity in rat thalamocortical relay neurons. AB - Modulation of the standing outward current (I (SO)) by muscarinic acetylcholine (ACh) receptor (MAChR) stimulation is fundamental for the state-dependent change in activity mode of thalamocortical relay (TC) neurons. Here, we probe the contribution of MAChR subtypes, G proteins, phospholipase C (PLC), and two pore domain K(+) (K(2P)) channels to this signaling cascade. By the use of spadin and A293 as specific blockers, we identify TWIK-related K(+) (TREK)-1 channel as new targets and confirm TWIK-related acid-sensitve K(+) (TASK)-1 channels as known effectors of muscarinic signaling in TC neurons. These findings were confirmed using a high affinity blocker of TASK-3 and TREK-1, namely, tetrahexylammonium chloride. It was found that the effect of muscarinic stimulation was inhibited by M(1)AChR-(pirenzepine, MT-7) and M(3)AChR-specific (4-DAMP) antagonists, phosphoinositide-specific PLCbeta (PI-PLC) inhibitors (U73122, ET-18-OCH(3)), but not the phosphatidylcholine-specific PLC (PC-PLC) blocker D609. By comparison, depleting guanosine-5'-triphosphate (GTP) in the intracellular milieu nearly completely abolished the effect of MAChR stimulation. The block of TASK and TREK channels was accompanied by a reduction of the muscarinic effect on I (SO). Current-clamp recordings revealed a membrane depolarization following MAChR stimulation, which was sufficient to switch TC neurons from burst to tonic firing under control conditions but not during block of M(1)AChR/M(3)AChR and in the absence of intracellular GTP. These findings point to a critical role of G proteins and PLC as well as TASK and TREK channels in the muscarinic modulation of thalamic activity modes. PMID- 22083647 TI - Spinal cord glioneuronal tumor with neuropil-like islands with 1p/19q deletion in an adult with low-grade cerebral oligodendroglioma. AB - Glioneuronal tumor with neuropil-like islands (GTNI) is considered a rare variant of astrocytoma, characterized by discrete aggregates of cells expressing neuronal markers that punctuate a GFAP-positive glial background. Of the 24 published GTNI cases, only two occurred in adult spinal cords; none occurred concurrent with another CNS tumor; and none of those tested exhibited the 1p/19q deletion typical of oligodendroglioma. A 48-year-old man without significant past medical history was diagnosed with a WHO grade II oligodendroglioma by stereotactic biopsy of a lesion discovered after the patient suffered a generalized tonic-clonic seizure. By FISH analysis, this tumor exhibited the 1p/19q deletion present in up to 80% of oligodendrogliomas. The patient received 14 monthly cycles of temozolomide, and his cerebral tumor had a minor response. When the patient subsequently reported progressive paresthesias of his lower extremities, an MRI revealed an enhancing, cystic tumor of the thoracic spinal cord that was diagnosed as GTNI by histological analysis. By FISH analysis, this lesion exhibited the same 1p/19q deletion present in the concurrent cerebral oligodendroglioma. This case of a spinal cord GTNI with 1p/19q deletions constitutes the third report of a spinal cord GTNI in an adult patient; the first report of a GTNI in an individual with a separate CNS neoplasm; and the first report of a GTNI with 1p/19q deletions. This case establishes a potential genetic kinship between GTNI and oligodendroglioma that warrants further investigation. PMID- 22083648 TI - Characterization of a novel Xenopus tropicalis cell line as a model for in vitro studies. AB - Cell lines are useful tools to facilitate in vitro studies of many biological and molecular processes. We describe a new permanent fibroblast-type cell line obtained from disaggregated Xenopus tropicalis limb bud. The cell line population doubling time was ~24 h. Its karyotype was genetically stable with a chromosome number of 2n = 21 and a chromosome 10 trisomy. These cells could be readily transfected and expressed transgenes faithfully. We obtained stable transformants using transposon-based gene transfer technology. These cells responded to thyroid hormone and thus can provide a complementary research tool to study thyroid hormone signaling events. In conclusion, this cell line baptized "Speedy" should prove useful to couple in vitro and in vivo biological studies in the X. tropicalis frog model. PMID- 22083649 TI - Random BAC FISH of monocot plants reveals differential distribution of repetitive DNA elements in small and large chromosome species. AB - BAC FISH (fluorescence in situ hybridization using bacterial artificial chromosome probes) is a useful cytogenetic technique for physical mapping, chromosome marker screening, and comparative genomics. As a large genomic fragment with repetitive sequences is inserted in each BAC clone, random BAC FISH without adding competitive DNA can unveil complex chromosome organization of the repetitive elements in plants. Here we performed the comparative analysis of the random BAC FISH in monocot plants including species having small chromosomes (rice and asparagus) and those having large chromosomes (hexaploid wheat, onion, and spider lily) in order to understand a whole view of the repetitive element organization in Poales and Asparagales monocots. More unique and less dense dispersed signals of BAC FISH were observed in species with smaller chromosomes in both the Poales and Asparagales species. In the case of large-chromosome species, 75-85% of the BAC clones were detected as dispersed repetitive FISH signals along entire chromosomes. The BAC FISH of Lycoris did not even show localized repetitive patterns (e.g., centromeric localization) of signals. PMID- 22083650 TI - Functional characterization of sugarcane MYB transcription factor gene promoter (PScMYBAS1) in response to abiotic stresses and hormones. AB - The sugarcane (Saccharum officinarum) stress-related MYB transcription factor gene, ScMYBAS1, demonstrated induced response to water deficit and salt stress in our previous study. To elucidate its stress tolerance mechanism at the transcriptional level, we isolated and characterized the promoter (PScMYBAS1, 1,033 bp) flanking the 5' ScMYBAS1 coding region from the sugarcane genome. A series of PScMYBAS1 deletion derivatives from the transcription start site (-56, 152, -303, -442, -613, -777, -843, -1,033) was fused to the uidA reporter gene (GUS) and each deletion construct was analyzed by Agrobacterium-mediated transient transformation in tobacco leaves subjected to dehydration, salinity, cold, wounding, gibberellic acid (GA), salicylic acid (SA), and methyl jasmonic acid (MeJA). Deletion analysis of the promoter, PScMYBAS1, suggested that the 303 bp promoter region was required for basal expression. Promoter fragments, 777 bp or longer showed ~twofold to ~fourfold increased induction of GUS in response to abiotic stress (dehydration, salt, cold, wounding) and hormone (SA, MeJA) treatments. These findings further our understanding of the regulation of ScMYBAS1 expression and provide a new stress-inducible promoter system in transgenic plants. PMID- 22083651 TI - Determination of hydrate inhibitor in crude oil by nanoextraction-gas chromatography. AB - This work focused on the quantitation of methanol as a hydrate inhibitor in crude oil. The novelty is nanoextraction of a polar compound from a complex non-polar matrix and selection of the proper fiber with maximum selectivity, loading percent, and lifetime. This approach not only does not require specific instrumentation, such as multiple columns and selective detectors, but also has eliminated the use of organic solvent and avoids the insertion of water inside the GC columns. The objective is optimization of extraction conditions, GC adjustments, and data processing. Experiments were conducted on the real sample of Iranian offshore crude oil by a carboxen/PDMS fiber via GC equipped with a cross-linked polyethylene glycol column and flame ionization detector. The results revealed that this fiber adsorbed the alcohols among other light non polar compounds of crude oil. Moreover, the interference effects of ethanol were solved by proper selection of the thermal program. The LOD, LOQ, and linear range of this approach were determined to be 3.9, 12.9, and 14-229 ppm for methanol, respectively. Using the standard calibration and the standard addition methods, the relative errors of 1.6-7.2 and 5.3-14.0% were determined. PMID- 22083652 TI - Heuristic value of eclecticism in theory development: the case of Piagetian Vygotskian dialogue about proportional reasoning. AB - Koppe's proposition of four layers in theoretical building are used here in the exploration of a specific case of eclectic combination, the use of Piagetian and Vygotskian general approaches to the analysis of proportional reasoning as a cognitive mathematical ability. It is proposed here that the eclectic consideration of these contributions depends on the consideration of their specificity, in the sense that they highlight different aspects of the phenomenon under scrutiny, and also on the consideration of the coherence between this eclectic convergence and premises in terms of schools of thought under which each contribution is framed. We conclude proposing in accordance to S. Koppe's proposal that eclecticism can be valuable and heuristic in theory development, but this contribution will depend largely on the effort in establishing careful relations between the four layers of theory-building. PMID- 22083653 TI - What are the important decisions in the lives of german and Indian university students? The structure of real-life decision-making processes. AB - In intercultural research, bias is sometimes introduced when a methodological approach that was mostly developed within one of the cultures (usually the Western one) is chosen. Instead of identifying and controlling such bias after data collection and during analysis, eliminating and minimizing bias during planning and while conducting the research is much more advisable. Particularly cross-cultural decision-making research has been hindered by the lack of instruments that are equally applicable in different cultures, resulting in biased findings. We have proposed a methodology for comparing cultures that uses qualitative methods and have used it in a comparison of German and Indian students' most important decision-making situations. In the first study, we identified common and different decision-making situations and recommended major areas for further cross-cultural research on decision making. In the second study, we made an attempt to explore the factors underlying important decision making areas in the two cultures. Semi-structured interviews were conducted to look for strong similarities and differences between cultures. Transcribed interview data were analyzed qualitatively using thematic analysis. Several themes were identified and descriptions of factors influencing decision making were derived inductively from interviews with students. Similarities and differences are explained in detail and a further, quantitative survey in different cultures is recommended. PMID- 22083654 TI - Effects of individual differences on the efficacy of different distracters during visual sexual stimulation in women. AB - Distractions from sexual cues have been shown to decrease the sexual response, but it is unclear how distracters decrease sexual response. Individual differences may modulate the efficacy of distracters. Forty women viewed three sexual films while their labial temperature and continuous self-reported sexual arousal were monitored. One sexual film had simultaneous verbal distracters concerning dissatisfaction with one's physical appearance (higher salience distracter), a second had distracters concerning daily chores (lower salience distracter), and the third sexual film had no distracters. Participant's reporting greater relationship satisfaction and more communication with their partner about their own physical appearance were expected to decrease the efficacy (increased sexual arousal) of the distracters concerning physical appearance. Contrary to expectations, women who received less feedback about their body from their partners reported less sexual arousal during a sexual film with body distracters than a sexual film with general distracters or a sexual film with no distracters. All women exhibited lower labial temperature in Minutes 2 and 3 of the sexual film with body image distracters as compared to the other two sexual films. Possible explanations explored include self-verification theory and individual differences in the indicators that women consider when rating their sexual arousal. PMID- 22083655 TI - Online sexual activity: cross-national comparison between United States and Peruvian college students. AB - The current generation of college students commonly uses the Internet for myriad sexually-related purposes. Yet, it has been suggested that usage of the Internet for sexual purposes might lead to psychological problems. In this study, undergraduate students from a public university in the U.S. (n = 320) and Peru (n = 251) completed questionnaires addressing their online sexual activity (OSA), psychological adjustment, and family environment and communication. Results indicated that Peruvians used the Internet significantly more than U.S. students to view sexually-explicit material (SEM), find sexual partners, and search for sex-related information. Men, irrespective of nationality, used the Internet to view SEM significantly more than women. Social support, religiosity, and erotophilia were found to moderate the relations between nationality and OSA. In absolute terms, both national groups, on average, engaged in OSA a relatively low number of hours each week. Further, no differences were found in maladjustment between those who engage in OSA and those who do not, suggesting that concerns over OSA are probably unwarranted. PMID- 22083656 TI - Risk reduction practices in men who have sex with men in Switzerland: serosorting, strategic positioning, and withdrawal before ejaculation. AB - The aim of this study was to identify predictors of intentional use of the HIV risk reduction practices of serosorting, strategic positioning, and withdrawal before ejaculation during unprotected anal intercourse (UAI) with casual partners. A cross-sectional survey pertaining to the Swiss HIV behavioral surveillance system, using an anonymous self-administered questionnaire, was conducted in 2007 in a self-selected sample of men having sex with other men (MSM). Analysis was restricted to participants with UAI with casual partner(s) (N = 410). Logistic regression was used to estimate factors associated with intentional use of serosorting, strategic positioning, and withdrawal before ejaculation. In the previous 12 months, 71% of participants reported having UAI with a casual partner of different or unknown HIV-status. Of these, 47% reported practicing withdrawal, 38% serosorting, and 25% strategic positioning. In the 319 participants with known HIV-status, serosorting was associated with frequent Internet use to find partners (OR = 2.32), STI (OR = 2.07), and HIV testing in the past 12 months (OR = 1.81). Strategic positioning was associated with HIV status (OR = 0.13) and having UAI with a partner of different or unknown HIV status (OR = 3.57). Withdrawal was more frequently practiced by HIV-negative participants or participants reporting high numbers of sexual partners (OR = 2.48) and having UAI with a partner of unknown or different serostatus (OR = 2.08). Risk reduction practices are widely used by MSM, each practice having its own specificities. Further research is needed to determine the contextual factors surrounding harm reduction practices, particularly the strategic or opportunistic nature of their use. PMID- 22083657 TI - "We belong to them": the costs of funding for rape crisis centers. AB - This research explores the transformation of rape crisis centers and whether directors, staff, interns, and volunteers see changes as beneficial or detrimental to rape crisis centers and the victims they serve. Data from 63 interviews with directors, staff, interns, and volunteers from six rape crisis centers located in four East Coast states indicate that although centers may have been formed for different reasons depending on when they opened, all have become more professional, rely less on volunteers, engage in more collaboration with other agencies, and have largely abandoned their traditional activism agenda. Traditional activism through political protests and membership in consciousness raising groups has been replaced by community education and outreach. Some of these changes are viewed as positive whereas others are viewed as negative. PMID- 22083658 TI - A test for psychometric function shift. AB - A nonparametric, small-sample-size test for the homogeneity of two psychometric functions against the left- and right-shift alternatives has been developed. The test is designed to determine whether it is safe to amalgamate psychometric functions obtained in different experimental sessions. The sum of the lower and upper p-values of the exact (conditional) Fisher test for several 2 * 2 contingency tables (one for each point of the psychometric function) is employed as the test statistic. The probability distribution of the statistic under the null (homogeneity) hypothesis is evaluated to obtain corresponding p-values. Power functions of the test have been computed by randomly generating samples from Weibull psychometric functions. The test is free of any assumptions about the shape of the psychometric function; it requires only that all observations are statistically independent. PMID- 22083659 TI - Clusterwise HICLAS: a generic modeling strategy to trace similarities and differences in multiblock binary data. AB - In many areas of the behavioral sciences, different groups of objects are measured on the same set of binary variables, resulting in coupled binary object * variable data blocks. Take, as an example, success/failure scores for different samples of testees, with each sample belonging to a different country, regarding a set of test items. When dealing with such data, a key challenge consists of uncovering the differences and similarities between the structural mechanisms that underlie the different blocks. To tackle this challenge for the case of a single data block, one may rely on HICLAS, in which the variables are reduced to a limited set of binary bundles that represent the underlying structural mechanisms, and the objects are given scores for these bundles. In the case of multiple binary data blocks, one may perform HICLAS on each data block separately. However, such an analysis strategy obscures the similarities and, in the case of many data blocks, also the differences between the blocks. To resolve this problem, we proposed the new Clusterwise HICLAS generic modeling strategy. In this strategy, the different data blocks are assumed to form a set of mutually exclusive clusters. For each cluster, different bundles are derived. As such, blocks belonging to the same cluster have the same bundles, whereas blocks of different clusters are modeled with different bundles. Furthermore, we evaluated the performance of Clusterwise HICLAS by means of an extensive simulation study and by applying the strategy to coupled binary data regarding emotion differentiation and regulation. PMID- 22083660 TI - OpenSesame: an open-source, graphical experiment builder for the social sciences. AB - In the present article, we introduce OpenSesame, a graphical experiment builder for the social sciences. OpenSesame is free, open-source, and cross-platform. It features a comprehensive and intuitive graphical user interface and supports Python scripting for complex tasks. Additional functionality, such as support for eyetrackers, input devices, and video playback, is available through plug-ins. OpenSesame can be used in combination with existing software for creating experiments. PMID- 22083661 TI - On the reliability, consistency, and method-specificity based on the CT-C(M-1) model. AB - In the present study, we discuss reliability, consistency, and method specificity based on the CT-C(M - 1) model, which provides clear definitions of trait and method factors and can facilitate parameter estimation. Properties of the reliability coefficient, the consistency coefficient, and the method-specificity coefficient of the summated score for a trait factor are addressed. The consistency coefficient and the method-specificity coefficient are both functions of the number of items, the average item consistency, and the average item method specificity. The usefulness of the findings is demonstrated in an alternative approach proposed for scale reduction. The approach, taking into account both traits and methods, helps identify the items leading to the maximum of convergent validity or method effects. The approach, illustrated with a simulated data set, is recommended for scale development based on multitrait-multimethod designs. PMID- 22083662 TI - Effect of Ginkgo biloba extract (GbE-761) on the survival of fasciocutaneous flaps in rats. AB - Cutaneous and fasciocutaneous flaps are used widely in the surgical reconstruction of various body segments, especially to cover exposed vital tissues. Partial or total necrosis of these flaps, secondary to insufficient tissue irrigation, is one possible complication. Therefore, investigations into antiplatelet aggregation, vasodilation and antioxidant properties are highly significant. The aim of the present study was to analyse the effect of GbE 761 on the survival of fasciocutaneous flaps in rats. For that purpose, GbE 761 was administered to 30 rats after the creation of 10 * 3 cm dorsal flaps on each animal. The rats were divided into three equal groups. GbE 761 was administered to Group A, starting immediately after surgery; Group B received it 24 h after the flap was cut; and Group C (controls) received 0.9% NaCl solution. The average area of necrosis was 29.53% in Group A, 26.25% in Group B and 46.12% in Group C. The difference between Groups B and C was statistically significant (p = 0.026). These initial findings suggest that GbE 761 administered on day 1 after surgery reduces the percentage of necrosis in fasciocutaneous flaps, relative to not giving GbE at all. PMID- 22083663 TI - Perspectives to breed for improved baking quality wheat varieties adapted to organic growing conditions. AB - Northwestern European consumers like their bread to be voluminous and easy to chew. These attributes require a raw material that is rich in protein with, among other characteristics, a suitable ratio between gliadins and glutenins. Achieving this is a challenge for organic growers, because they lack cultivars that can realise high protein concentrations under the relatively low and variable availability of nitrogen during the grain-filling phase common in organic farming. Relatively low protein content in wheat grains thus needs to be compensated by a high proportion of high-quality protein. Organic farming therefore needs cultivars with genes encoding for optimal levels of glutenins and gliadins, a maximum ability for nitrogen uptake, a large storage capacity of nitrogen in the biomass, an adequate balance between vegetative and reproductive growth, a high nitrogen translocation efficiency for the vegetative parts into the grains during grain filling and an efficient conversion of nitrogen into high quality proteins. In this perspective paper the options to breed and grow such varieties are discussed. PMID- 22083664 TI - Comparison of aortic and carotid arterial stiffness parameters in patients with verified coronary artery disease. AB - BACKGROUND: Arterial stiffness parameters are commonly used to determine the development of atherosclerotic disease. The independent predictive value of aortic stiffness has been demonstrated for coronary events. HYPOTHESIS: The aim of our study was to compare regional and local arterial functional parameters measured by 2 different noninvasive methods in patients with verified coronary artery disease (CAD). We also compared and contrasted these stiffness parameters to the coronary SYNTAX score in patients who had undergone coronary angiography. METHODS: In this study, 125 CAD patients were involved, and similar noninvasive measurements were performed on 125 healthy subjects. The regional velocity of the aortic pulse wave (PWVao) was measured by a novel oscillometric device, and the common carotid artery was studied by a Doppler echo-tracking system to determine the local carotid pulse wave velocity (PWVcar). The augmentation index (AIx), which varies proportionately with the resistance of the small arteries, was recorded simultaneously. RESULTS: In the CAD group, the PWVao and aortic augmentation index (Alxao) values increased significantly (10.1 +/- 2.3 m/sec and 34.2% +/- 14.6%) compared to the control group (9.6 +/- 1.5 m/sec and 30.9% +/- 12%; P < 0.05). We observed similar significant increases in the local stiffness parameters (PWVcar and carotid augmentation index [Alxcar]) in patients with verified CAD. Further, we found a strong correlation for PWV and AIx values that were measured with the Arteriograph and those obtained using the echo-tracking method (r = 0.57, P < 0.001 for PWV; and r = 0.65, P < 0.001 for AIx values). CONCLUSIONS: Our results indicate that local and regional arterial stiffness parameters provide similar information on impaired arterial stiffening in patients with verified CAD. PMID- 22083665 TI - The use of N-methylpyrrolidone as a cosolvent and oxidant in pharmaceutical stress testing. AB - The use of N-methylpyrrolidone (NMP) as an oxidant and cosolvent in pharmaceutical stress testing (forced degradation) is examined. Various active pharmaceutical ingredients were heated in NMP-water solutions under nitrogen, air, and oxygen and then analyzed by high-performance liquid chromatography, usually with ultraviolet diode array detection and mass spectrometry detection. In some cases, degradation products were isolated and characterized by nuclear magnetic resonance. The NMP-water-air-heat system provided oxidative and hydrolytic degradation products. The observed oxidation products were consistent with products expected from free radical autoxidation, reactions with hydroperoxides, and possibly singlet oxygen. Oxidative and hydrolytic pathways could be distinguished by comparison of the reactions carried out under air/oxygen and nitrogen. In many cases, the oxidation products observed during stress testing were also observed during formal stability studies of drug products. The NMP-water-air-heat stress condition facilitates various oxidative degradation pathways, which are often relevant to drug product on stability. This approach facilitates stability-indicating method development and helps elucidate degradation pathways. PMID- 22083666 TI - Murine model of neuromuscular electrical stimulation on squamous cell carcinoma: potential implications for dysphagia therapy. AB - BACKGROUND: Dysphagia is a potential consequence of treatment for head and neck cancer. Neuromuscular electrical stimulation (NMES) has evolved as a treatment option, with the goal of improved swallow function in patients with chronic dysphagia. However, the effects of NMES on tumorigenicity are unknown and often confound the initiation of this therapy, potentially limiting its efficacy in treating patients with head and neck cancer. METHODS: Squamous cell carcinoma was grown in the flank of athymic, nude mice. Mice were randomized into treatment and control groups; the experimental group received daily NMES directly to the flank for 8 days. RESULTS: Tumor volumes, recorded on days 0, 3, 7, and 10, demonstrated no significant differences between groups on each day of measurement. Immunohistochemical analysis of apoptosis, proliferation, and vascularization also failed to demonstrate statistically significant differences between treated and untreated groups. CONCLUSIONS: NMES does not promote the growth of underlying tumor in our model. These data may provide preliminary evidence that applying electrical stimulation over the muscles of the anterior neck does not increase the risk of tumorigenicity. Early initiation of NMES in this challenging population may be feasible from an oncologic standpoint. PMID- 22083667 TI - Peripheral assessment of the genes AQP4, PBP and TH in patients with Parkinson's disease. AB - Parkinson's disease (PD) typically appears in late middle-aged and in elderly persons progressing over a period of several years. The characteristic pathological features of PD patients include defective motor function and cognitive function affecting the quality of life of PD patients. Oxidative stress is considered to a play a central role along with various other factors in the pathogenesis of PD and the incidence and prevalence of the disease is incessantly increasing worldwide. The objective of the current study was to assess mRNA expressional changes of AQP4, TH and PBP in blood samples of control and patients with PD. The study included 30 healthy controls and 90 PD patients subjected to treatment through the entire period of the study. RNA isolation was carried out using blood samples of the subjects recruited in the study and used for RT-PCR analysis of AQP4, TH as well as PBP. The mRNA expressions of AQP4 and TH were found to be reduced whereas that of PBP was found to be elevated when compared with those of healthy control samples. The statistically analysed data were presented which could be helpful for appreciation of PD pathology reflecting in the blood samples of PD population. PMID- 22083669 TI - Characterization of novel germline c-kit gene mutation, KIT-Tyr553Cys, observed in a family with multiple gastrointestinal stromal tumors. AB - We found a novel type germline mutation at exon 11 of the c-kit gene, which results in a substitution of Tyr to Cys at codon 553 of the c-kit gene product (KIT-Tyr553Cys), in a 68-year-old female patient with multiple gastrointestinal stromal tumors (GISTs). In the present study, we carried out mutational analysis in her family members to determine the carriers and characterized the mutation by introducing the corresponding mutation (murine KIT-Tyr552Cys) into expression vector possessing murine c-kit cDNA. Mutational analysis of peripheral blood leukocytes of her family members revealed that a 44-year-old son had the same mutation, but at present he had neither apparent symptoms nor images of multiple GISTs. By transfection with the expression vector possessing the murine mutant c kit cDNA, interleukin-3-dependent Ba/F3 murine lymphoid cells started growing autonomously without any growth factors, indicating that the mutation was considered to be of gain-of-function. Imatinib, a small molecule of tyrosine kinase inhibitor, effectively inhibited autophosphorylation of KIT-Tyr552Cys. Nilotinib, another small molecule of the KIT inhibitor, also effectively inhibited autophosphorylation of KIT-Tyr552Cys. In fact, proliferation of Ba/F3 cells expressing KIT-Tyr552Cys was effectively inhibited by both imatinib and nilotinib. These findings indicate that the novel type human KIT-Tyr553Cys mutation is the cause of the present familial and multiple GISTs, and that both imatinib and nilotinib might effectively inhibit the growth of GISTs developing in the patients of this family. PMID- 22083668 TI - The role of the Golgi-resident SPCA Ca2+/Mn2+ pump in ionic homeostasis and neural function. AB - Recent evidence highlights the functional importance of the Golgi apparatus (GA) in neurological diseases. The functions of the mammalian GA, in addition to the processing and transport of cargo, also include ionic homeostasis. Besides Ca2+ release channels which serves GA as an agonist-sensitive intracellular Ca2+ store, and Ca2+-binding proteins, the GA contains Ca2+-uptake mechanisms consisting of the well-known sarco-endoplasmic reticulum Ca2+-transport ATPases and the much less characterized secretory-pathway Ca2+-transport ATPases (SPCA). SPCA can transport both Ca2+ and Mn2+ into the Golgi lumen and therefore is involved in the cytosolic and intra-Golgi Ca2+ and Mn2+ homeostasis. It has shown that both of the mRNA and protein of SPCAs are highly expressed in brain. In addition, brain is the region with the highest activity of SPCA isoforms, which may be related to the involvement of Ca2+ and Mn2+ homeostasis in neural functions. In this review, we compile some recent findings showing that the SPCA isoform plays a much more important role in intracellular ionic homeostasis than previously anticipated and illustrating the involvement of SPCA isoforms in certain neurophysiological or neuropathological process. We are interested in gaining insight into the intricate role of the SPCA pumps to explain the GA specific functions in neurological disorders. PMID- 22083670 TI - Wnt activation is implicated in glioblastoma radioresistance. AB - Glioblastoma (GBM) patients have dismal median survival even with the most rigorous treatments currently available. Radiotherapy is the most effective non surgical therapy for GBM patients; however, patients succumb due to tumor recurrence within a year. To develop a curative therapeutic approach, we need to better understand the underlying molecular mechanism of radiation resistance in GBM. Towards this goal, we developed an in vivo orthotopic GBM model system that mimics the radiation response of human GBM, using both established-GBM cell line and patient-derived freshly dissociated GBM specimen. In-vivo ionizing radiation (IR) treatment prolonged the survival of mice with intracranical tumor derived from U373MG, but failed to prevent tumor recurrence. U373MG and GBM578 cells isolated after in-vivo IR (U373-IR and 578-IR) were more clonogenic and enriched with stem cell-like characteristics, compared with mock-treated control tumor cells. Transcriptomic analyses and quantitative real-time reverse-transcription PCR analyses using these matched GBM cells before and after radiation treatment revealed that Wnt pathways were preferentially activated in post-IR GBM cells. U373-IR cells and 578-IR were enriched with cells positive for both active beta catenin (ABC) and Sox2 population, and this subpopulation was further increased after additional in-vitro radiation treatment, suggesting that radiation resistance of GBM is mediated due, in part, to the activation of stem cell associated pathways including Wnt. Finally, pharmacological and siRNA inhibition of Wnt pathway significantly decreased the survival and clonogenicity of GBM cells and reduced their ABC(+)/Sox2(+) population. Together, these data suggest that Wnt activation is a molecular mechanism to confer GBM radioresistance and an important therapeutic target. PMID- 22083671 TI - Bevacizumab attenuates major signaling cascades and eIF4E translation initiation factor in multiple myeloma cells. AB - Multiple myeloma (MM), a malignancy of plasma cells, remains fatal despite introduction of novel therapies, partially due to humoral factors, including vascular endothelial growth factor (VEGF), in their microenvironment. The aim of this study was to explore the efficacy of anti-VEGF treatment with bevacizumab directly on MM cells. Particular attention was directed to the affect of VEGF inhibition on protein translation initiation. Experiments were conducted on MM cells (lines, bone marrow (BM) samples) cultured on plastic. Inhibition of VEGF was achieved with the clinically employed anti-VEGF antibody, bevacizumab, as a platform and its consequences on viability, proliferation, and survival was assessed. VEGF downstream signals of established importance to MM cell biology were assayed as well, with particular emphasis on translation initiation factor eIF4E. We showed that blocking VEGF is deleterious to the MM cells and causes cytostasis. This was evidenced in MM cell lines, as well as in primary BM samples (BM MM). A common bevacizumab-induced attenuation of critical signaling effectors was determined: VEGFR1, mTOR, c-Myc, Akt, STAT3, (cell lines) and eIF4E translation initiation factor (lines and BM). ERK1/2 displayed a variegated response to bevacizumab (lines). Utilizing a constitutively Akt-expressing MM model, we showed that the effect of bevacizumab on viability and eIF4E status is Akt-dependent. Of note, the effect of bevacizumab was achieved with high concentrations (2 mg/ml), but was shown to be specific. These findings demonstrate that bevacizumab has a direct influence on major pathways critically activated in MM that is independent from its established effect on angiogenesis. The cytostatic effect of VEGF inhibition on MM cells underscores its potential in combined therapy, and our findings, regarding its influence on translation initiation, suggest that drugs that unbalance cellular proteostasis may be particularly effective. PMID- 22083672 TI - Whole again: the practice of foreskin restoration. PMID- 22083673 TI - No regulatory double standard for natural health products. PMID- 22083674 TI - The role of seroepidemiology in the comprehensive surveillance of vaccine preventable diseases. PMID- 22083675 TI - WHO mulls phase out of vaccine linked to polio outbreaks. PMID- 22083677 TI - Provinces to support national clinical guidelines strategy. PMID- 22083678 TI - Could parenting programs lead to lower health care costs in future generations? PMID- 22083679 TI - Longitudinally extensive transverse myelitis: a catastrophic presentation of a flare-up of systemic lupus erythematosus. PMID- 22083680 TI - Family medicine's obligation to society. PMID- 22083682 TI - Busting myths about guidelines. PMID- 22083681 TI - Childhood aggression, withdrawal and likeability, and the use of health care later: a longitudinal study. AB - BACKGROUND: Literature suggests that early patterns of aggressive behaviour in both girls and boys are predictive of a variety of health risks in adulthood. However, longitudinal examination of the predictive links between childhood aggression, negative physical health outcomes in adulthood and overall use of health care has not been done. We looked at use of health care and a variety of physical health outcomes in adulthood to extend the current body of knowledge regarding the long-term negative sequelae of childhood aggression. METHODS: Participants of the Concordia Longitudinal Risk Project were eligible for the current study if they had received medical care in the province of Quebec between 1992 and 2006, and if we were able to retrieve their medical and education records. Our primary outcome was use of the health care system, as determined using records from the Regie de l'assurance maladie du Quebec and the Ministere de la sante et des services sociaux. Our controlled variables were socioeconomic status of the neighbourhood in which participants lived in 1986 and level of education. We used hierarchical multiple regression to explore the association between childhood behaviour and physical health in adulthood. RESULTS: During the 15-year period studied, childhood agression corresponded to an increase in medical visits (8.1% per 1 standard deviation increase in agression), and injuries (10.7%) or lifestyle-related illnesses (44.2%), visits to specialists (6.2%) and visits to emergency departments (12.4%). We saw a positive relation between social withdrawal during childhood and government-funded visits to dentists. Peer-rated likeability during childhood showed negative relations with use of health care (overall), medical visits due to injuries and government funded visits to dentists. INTERPRETATION: Childhood aggression is a health risk that should be considered when designing interventions to improve public health and diminish the costs of medical services, particularly when considering interventions targeting children and families. PMID- 22083683 TI - Recurrent appendicitis after appendectomy. PMID- 22083684 TI - Incidence of bleeding from gastroduodenal ulcers in patients with end-stage renal disease receiving hemodialysis. AB - BACKGROUND: Few large population-based studies have compared the incidence of bleeding of gastroduodenal ulcers between patients with and without end-stage renal disease. We investigated the association between ulcer bleeding and end stage renal disease in patients receiving hemodialysis, and we sought to identify risk factors for ulcer bleeding. METHODS: We performed a nationwide seven-year population study using data from the National Health Insurance Research Database in Taiwan. We identified 36 474 patients with end-stage renal disease who were receiving hemodialysis, 6320 patients with chronic kidney disease and 36 034 controls matched for age, sex and medication use. We performed log-rank testing to analyze differences in survival time without ulcer bleeding among the three groups. We performed Cox proportional hazard regressions to evaluate the risk factors for ulcer bleeding among the three groups and to identify risk factors in patients receiving hemodialysis. RESULTS: Patients receiving hemodialysis and those with chronic kidney disease had a significantly higher incidence of ulcer bleeding than controls had (p<0.001). Hemodialysis (hazard ratio [HR] 5.24, 95% confidence interval [CI] 4.67-5.86) and chronic kidney disease (HR 1.95, 95% CI 1.62-2.35) were independently associated with an increased risk of ulcer bleeding. Diabetes mellitus, coronary artery disease, cirrhosis and use of nonsteroidal anti-inflammatory drugs were risk factors for ulcer bleeding in patients with end-stage renal disease who were receiving hemodialysis INTERPRETATION: Patients with end-stage renal disease who are receiving hemodialysis had a high risk of ulcer bleeding. Diabetes mellitus, coronary artery disease, cirrhosis and the use of nonsteroidal anti-inflammatory drugs were important risk factors for ulcer bleeding in these patients. PMID- 22083685 TI - The eggshell in the C. elegans oocyte-to-embryo transition. AB - In egg-laying animals, embryonic development takes place within the highly specialized environment provided by the eggshell and its underlying extracellular matrix. Far from being simply a passive physical support, the eggshell is a key player in many early developmental events. Herein, we review current understanding of eggshell structure, biosynthesis, and function in zygotic development of the nematode, C. elegans. Beginning at sperm contact or entry, eggshell layers are produced sequentially. The earlier outer layers are required for secretion or organization of inner layers, and layers differ in composition and function. Developmental events that depend on the eggshell include polyspermy barrier generation, high fidelity meiotic chromosome segregation, osmotic barrier synthesis, polar body extrusion, anterior-posterior polarization, and organization of membrane and cortical proteins. The C. elegans eggshell is proving to be an excellent, tractable system to study the molecular cues of the extracellular matrix that instruct cell polarity and early development. PMID- 22083686 TI - One- and comprehensive two-dimensional high-performance liquid chromatography analysis of alkylphenol polyethoxylates. AB - High-performance liquid chromatography (HPLC) analysis of alkylphenol polyethoxylates (APnEOs) in one-dimensional (1-D) mode usually separates either the ethoxy or alkyl moiety distribution and requires different modes for adequate resolution. Simultaneous complete separation of variable ethoxymer chain lengths and variable alkyl end groups using 1-D-HPLC has not been reported and suggests that multidimensional (MDLC) or comprehensive two-dimensional liquid chromatography (LC*LC) might offer a suitable separation approach for this goal. This study compares different separation modes--normal phase LC (NPLC), reversed phase LC (RPLC) and hydrophilic interaction chromatography (HILIC)--in terms of separation for alkyl and ethoxy distributions. RPLC provided adequate separation of octyl and nonyl APnEOs using an isocratic elution program and was selected as second dimension ((2)D) for LC*LC. NPLC offered better resolution than HILIC; however, non-polar NPLC solvent immiscibility with RPLC mobile phases leads to HILIC being chosen as first dimension ((1)D). The HILIC*RPLC system was evaluated by analysis of four APnEO mixtures. Complete simultaneous separation of APnEOs into individual oligomers, with each alkyl end group resolved, demonstrated the capability of the LC*LC method. Different descriptors and metrics for assessing system orthogonality were investigated to evaluate HILIC*RPLC performance. A relatively high dimensionality of 1.76 was demonstrated. PMID- 22083687 TI - Antinociceptive effect of [Met5]enkephalin semicarbazide is not affected by dipeptidyl carboxypeptidase-I. AB - Dipeptidyl carboxypeptidase-I is an enzyme involved in the biological degradation of enkephalins. It has been suggested that C-terminal amidation of enkephalins enhances their resistance to dipeptidyl carboxypeptidase-I-mediated biodegradation. In this study, a novel [Met5]enkephalin amide (MEA) analogue [Met5]enkephalin (ME)-semicarbazide synthesized by another laboratory in our group was assessed for its antinociceptive effects compared with ME-ethylamide, MEA and ME, using tail flick test. To protect the administered drugs from biodegradation, rats were pretreated with peptidase inhibitors including amastatin, phosphoramidon and captopril. Then captopril (dipeptidyl carboxypeptidase-I inhibitor) was deleted from the peptidase inhibitors' combination for evaluating in vivo resistance of the synthetic drugs to dipeptidyl carboxypeptidase-I. According to the results, ME-semicarbazide and MEA were resistant enough to dipeptidyl carboxypeptidase-I to exert their strong antinociception following intrathecal administration even in the absence of captopril, whereas the antinociceptive effects produced by ME-ethylamide (10 nmol) were abolished in rats not pretreated with captopril, indicating that significant amounts of the ME-ethylamide were degraded by dipeptidyl carboxypeptidase-I. Replacement of the amide moiety of MEA with semicarbazide provides a new ME derivative, with high analgesic effects as well as more resistance to dipeptidyl carboxypeptidase-I-mediated biodegradation. PMID- 22083689 TI - Surgical management of muscular trabecular ventricular septal defects. AB - Despite recent advances in diagnosis, surgical techniques, and postoperative care of children with congenital cardiac defects, muscular trabecular ventricular septal defects (VSDs) are still a therapeutic challenge. Among these defects, it is more difficult to achieve secure and complete closure of low trabecular or apical VSDs because of the presence of numerous muscular trabeculations overlying the defect. When they are associated with "Swiss cheese"-type of VSDs, it is almost impossible to visualize the true edges of the defect through the transatrial approach. Consequently, there remains an unacceptable incidence of mortality and morbidity when compared to those that occur with closure of the usual perimembranous VSD. Although various techniques for closure of these difficult trabecular VSDs have been attempted, there is still a significant incidence of complications in the surgical management of trabecular VSDs, mostly significant residual shunts, a need for multiple reoperations, and severe left ventricular dysfunction. This article describes the anatomical details and classification of muscular trabecular VSDs. It also reviews several techniques currently utilized and their outcomes. PMID- 22083690 TI - Two-staged treatment strategy in patients with severe carotid or cerebrovascular diseases undergoing coronary artery bypass grafting. AB - PURPOSE: There is no clear consensus on how to treat patients undergoing coronary artery bypass grafting (CABG) who have severe concomitant carotidcerebral artery stenosis. The aim of this study was to evaluate our surgical results in patients with severe carotid and/or cerebrovascular disease undergoing CABG. METHODS: Between October 2003 and April 2009, a total of 47 such patients were treated at our institution with the following strategies: (1) protective carotid artery stenting for severe carotid stenosis performed either before (n = 20) or after (n = 5) CABG or (2) a superficial temporal artery-middle cerebral artery anastomosis procedure followed by CABG if indicated (n = 4). Off-pump CABG was performed in 75% of the patients. RESULTS: There were no major perioperative strokes or in hospital deaths; however, three patients had transient ischemic attacks and two had minor strokes during the early post-CABG period. All of the patients with postoperative cerebrovascular events had had unilateral carotid artery occlusion. There were no late deaths during the follow-up period (up to 6 years, with a mean of 27 months). However, major adverse cardiocerebrovascular events (MACCE) occurred in seven patients (14.9%). The rates of freedom from MACCE at 1 and 3 years were 92% and 74%, respectively. CONCLUSION: It appears that our two-staged approach is safe and may reduce the risk of postoperative cerebrovascular events. PMID- 22083691 TI - Systolic anterior motion after mitral valve repair: predicting factors and management. AB - PURPOSE: The aim of this study was to determine the mechanism of systolic anterior motion (SAM) after mitral valve (MV) repair by analyzing the clinical data of patients with MV repair. METHODS: A total of 104 MV repairs were performed for patients with isolated degenerative posterior leaflet prolapse. Eight patients (7.7%) developed SAM with severe mitral regurgitation. We compared the preoperative and intraoperative findings of the two groups (8 patients in the SAM group, 96 in the non-SAM group) and reported the clinical courses of the SAM patients. RESULTS: Preoperative left ventricular end-diastolic and end-systolic diameters were significantly smaller and the preoperative left ventricular ejection fraction was significantly greater in the SAM group than in the non-SAM group. The number of patients with a sigmoid septum and the number with anterior leaflet-septal contact (LSC) during diastole were significantly larger in the SAM group. Incidence of billowing posterior leaflet, prolapsed segments, and operative techniques were comparable for the two groups. SAM improved with correction of hemodynamic status in four patients. In four other patients secondary cardiopulmonary bypass was required to resolve SAM. SAM resolved with additional repairs in two patients, whereas the other two required MV replacement. Of the six patients in whom conservative treatment or re-repair was successful, one had recurrent SAM 3 months after surgery. CONCLUSION: The sigmoid septum and LSC may predict SAM after MV repair. A strict follow-up is imperative for patients with persistent or recurrent SAM. PMID- 22083692 TI - Effect of CD4+ T-lymphocyte count on hospital outcome of elective general thoracic surgery patients with human immunodeficiency virus. AB - PURPOSE: Traditionally, the chief surgical indicator for human immunodeficiency virus (HIV)-infected patients was the CD4-positive T-lymphocyte count; however, there is no current consensus. Reports published after 2006 indicated that HIV infected patients had a higher incidence of postoperative pneumonia and higher 12 month mortality rates. In addition, CD4 counts had no relation to the in-hospital outcome. Therefore, we retrospectively examined all of the previous patients who underwent operations in our department on the basis of these findings. METHODS: Regardless of the initiation of highly active anti-retroviral therapy (HAART), we retrospectively reviewed 10 general thoracic surgeries performed in our department according to the CD4 cell count, HIV-ribonucleic acid (RNA) viral load, time of HAART initiation, operating time, amount of blood, postoperative course, and period of observation. RESULTS: There was no incidence of postoperative pneumonia or wound infection. There were also no complications during the perioperative period. One patient died 7 months after surgery. CONCLUSION: Our retrospective study demonstrates that the indicator for elective general thoracic surgery is not the CD4-positive T-lymphocyte count and that the initiation of HAART may reduce the 12-month mortality rates. In HIV-positive patients, regardless of the CD4-positive T-lymphocyte count, surgeons can operate in the same manner as they would with HIV-negative patients. PMID- 22083693 TI - Surgical treatment for gastrointestinal metastasis of non-small-cell lung cancer after pulmonary resection. AB - PURPOSE: Gastrointestinal metastasis is not common in recurrent non-small-cell lung cancer (NSCLC) patients. There is thus limited information on clinical outcome for these patients. This report presents the clinical characteristics and outcomes of patients with gastrointestinal metastasis after pulmonary resection. METHODS: The study retrospectively analyzed nine NSCLC patients with gastrointestinal metastases. RESULTS: Gastrointestinal metastases were observed in the small intestine (n = 4), colon or rectum (n = 4), and stomach (n = 1). All of the patients were symptomatic. The median survival after gastrointestinal recurrence was 10.8 months. Gastrointestinal surgery was performed in five patients, whereas no cancer treatment was indicated in the remaining four patients. Three patients who underwent surgery for a solitary metastasis survived for more than 2 years after surgery with no other recurrence. CONCLUSION: Surgical resection of gastrointestinal metastasis is indicated not only for symptom relief but also for providing a potentially long-term survival if the patients are properly selected. PMID- 22083694 TI - Reoperation for prosthetic ventricular septal defect patch endocarditis: long term results with an autologous atrial septal patch. AB - Treatment of prosthetic patch endocarditis after closure of a ventricular septal defect is challenging. It is essential to reduce inflammation and prevent recurrence of endocarditis. We report a successful case of reclosure of a ventricular septal defect using an autologous atrial septal patch taken from the fossa ovalis. There were no complications, and the long-term results were satisfactory. The autologous septal patch might be a promising material for prosthetic patch endocarditis. PMID- 22083695 TI - Temporary ventricular overdrive pacing for electrical storm after coronary artery bypass grafting. AB - A 57-year-old man who had been receiving chemotherapy for multiple myeloma complained of chest pain and was diagnosed with coronary artery disease. Coronary artery bypass grafting without cardiopulmonary bypass was performed smoothly, and extubation was done in the operating room. The next evening, cluster of ventricular tachycardia and fibrillation triggered by ventricular premature contractions occurred and required multiple electrical defibrillations. Despite intravenous administration of lidocaine, amiodarone, magnesium, and beta-blocker, the storm sustained and was suppressed only by temporary ventricular overdrive pacing. He was discharged on foot. PMID- 22083696 TI - Isolated right diaphragmatic rupture following blunt trauma. AB - Blunt diaphragmatic injuries are usually caused by blunt trauma or penetrating injuries. The diagnosis may be delayed or missed because of the confusing clinical and radiographic findings and the presence of multiple associated injuries. We report the case of an isolated right diaphragm rupture in a 56-year old man who sustained blunt thoracic trauma after car accident 2 weeks before presentation. No other injuries were detected, and he was subjected to laparotomy. Diaphragmatic rupture is perceived as an emergency entity. The late appearance of such an injury, without other accompanying injuries, is rare and should be in mind by clinicians treating trauma patients who have a delayed presentation after the injury. PMID- 22083697 TI - Benign fibrous histiocytoma arising from the intercostal space. AB - Benign fibrous histiocytoma is a tumor of unknown etiology that is believed to be of mixed fibroblastic and histiocytic origin. Deep benign fibrous histiocytomas are most commonly found in the lower limbs or the head and neck region; it is relatively rare that they are seen in the intercostal space. Only six case reports of this entity are described in the literature. We report a 20-year-old woman who suffered from a painless swelling in the left chest wall, with a computed tomographic correlation. The lesion was totally excised, and histopathology revealed a benign fibrous histiocytoma. This is the first case of a benign fibrous histiocytoma that arose from the intercostal space reported in the English-language literature. The six cases reported in the medical literature are also discussed. PMID- 22083698 TI - Bronchopulmonary foregut malformation. AB - Bronchopulmonary foregut malformation (BPFM) is a rare anomaly of accessory pulmonary tissue that usually arises from esophagus or stomach. We present a case of extralobar pulmonary sequestration (ELS) connecting with the esophagus by a cyst, the inner wall of which is lined with squamous epithelium or respiratory epithelium. BPFM is sometimes used to group a number of ventral anomalies of accessory pulmonary tissue. The term currently refers specifically to those lesions composed of sequestrations that retain communication with the gastrointestinal tract. Usually the communication is a well-formed muscular tube lined with stratified squamous or columnar epithelium. The presence of both epithelia in a communication that is a component of the BPFM suggests embryogenesis. We describe an adult with BPFM composed of ELS and a connecting stalk to the esophagus by a foregut cyst that contains both squamous epithelium and respiratory epithelium. PMID- 22083699 TI - Postoperative bronchial stump fistula after lobectomy: response to occlusion with polyglycolic acid mesh and fibrin glue via bronchoscopy. AB - Bronchial stump fistula after resection of lung cancer is an extremely difficult to treat postoperative complication. Endoscopic fistula closure is a favorable alternative, potentially avoiding major surgical intervention. an 80-year-old man underwent curative resection of squamous cell carcinoma by left upper lobectomy of the lung. The patient suddenly developed massive subcutaneous emphysema on postoperative day 10. Bronchoscopy revealed a fistula about 3 mm in diameter at the lateral edge of the bronchial stump. Concentrated fibrinogen 0.5 ml (fluid A) was sprinkled on the bronchial fistula initially, and then pieces of polyglycolic acid mesh presoaked in fluid A or fluid B (thrombin) of the fibrin glue were pushed with biopsy forceps into the fistula in an alternating fashion (A->B->A >B) under endotracheal local anesthesia. Air leakage was stopped, and the patient did not develop empyema. Particularly for patients in poor general condition, our noninvasive technique seems to serve as a therapy of first choice. PMID- 22083700 TI - The enolase of Borrelia burgdorferi is a plasminogen receptor released in outer membrane vesicles. AB - The agent of Lyme disease, Borrelia burgdorferi, has a number of outer membrane proteins that are differentially regulated during its life cycle. In addition to their physiological functions in the organism, these proteins also likely serve different functions in invasiveness and immune evasion. In borreliae, as well as in other bacteria, a number of membrane proteins have been implicated in binding plasminogen. The activation and transformation of plasminogen into its proteolytically active form, plasmin, enhances the ability of the bacteria to disseminate in the host. Outer membrane vesicles of B. burgdorferi contain enolase, a glycolytic-cycle enzyme that catalyzes 2-phosphoglycerate to form phosphoenolpyruvate, which is also a known plasminogen receptor in Gram-positive bacteria. The enolase was cloned, expressed, purified, and used to generate rabbit antienolase serum. The enolase binds plasminogen in a lysine-dependent manner but not through ionic interactions. Although it is present in the outer membrane, microscopy and proteinase K treatment showed that enolase does not appear to be exposed on the surface. However, enolase in the outer membrane vesicles is accessible to proteolytic degradation by proteinase K. Samples from experimentally and tick-infected mice and rabbits as well as from Lyme disease patients exhibit recognition of enolase in serologic assays. Thus, this immunogenic plasminogen receptor released in outer membrane vesicles could be responsible for external proteolysis in the pericellular environment and have roles in nutrition and in enhancing dissemination. PMID- 22083701 TI - Novel protein substrates of the phospho-form modification system in Neisseria gonorrhoeae and their connection to O-linked protein glycosylation. AB - The zwitterionic phospho-form moieties phosphoethanolamine (PE) and phosphocholine (PC) are important components of bacterial membranes and cell surfaces. The major type IV pilus subunit protein of Neisseria gonorrhoeae, PilE, undergoes posttranslational modifications with these moieties via the activity of the pilin phospho-form transferase PptA. A number of observations relating to colocalization of phospho-form and O-linked glycan attachment sites in PilE suggested that these modifications might be either functionally or mechanistically linked or interact directly or indirectly. Moreover, it was unknown whether the phenomenon of phospho-form modification was solely dedicated to PilE or if other neisserial protein targets might exist. In light of these concerns, we screened for evidence of phospho-form modification on other membrane glycoproteins targeted by the broad-spectrum O-linked glycosylation system. In this way, two periplasmic lipoproteins, NGO1043 and NGO1237, were identified as substrates for PE addition. As seen previously for PilE, sites of PE modifications were clustered with those of glycan attachment. In the case of NGO1043, evidence for at least six serine phospho-form attachment sites was found, and further analyses revealed that at least two of these serines were also attachment sites for glycan. Finally, mutations altering glycosylation status led to the presence of pptA-dependent PC modifications on both proteins. Together, these results reinforce the associations established in PilE and provide evidence for dynamic interplay between phospho-form modification and O-linked glycosylation. The observations also suggest that phospho-form modifications likely contribute biologically at both intracellular and extracellular levels. PMID- 22083702 TI - RrgB321, a fusion protein of the three variants of the pneumococcal pilus backbone RrgB, is protective in vivo and elicits opsonic antibodies. AB - Streptococcus pneumoniae pilus 1 is present in 30 to 50% of invasive disease causing strains and is composed of three subunits: the adhesin RrgA, the major backbone subunit RrgB, and the minor ancillary protein RrgC. RrgB exists in three distinct genetic variants and, when used to immunize mice, induces an immune response specific for each variant. To generate an antigen able to protect against the infection caused by all pilus-positive S. pneumoniae strains, we engineered a fusion protein containing the three RrgB variants (RrgB321). RrgB321 elicited antibodies against proteins from organisms in the three clades and protected mice against challenge with piliated pneumococcal strains. RrgB321 antisera mediated complement-dependent opsonophagocytosis of piliated strains at levels comparable to those achieved with the PCV7 glycoconjugate vaccine. These results suggest that a vaccine composed of RrgB321 has the potential to cover 30% or more of all pneumococcal strains and support the inclusion of this fusion protein in a multicomponent vaccine against S. pneumoniae. PMID- 22083703 TI - The Acinetobacter baumannii biofilm-associated protein plays a role in adherence to human epithelial cells. AB - Acinetobacter baumannii is a significant source of nosocomial infections worldwide. This bacterium has the ability to survive and persist on multiple abiotic surfaces in health care facilities, and once a focus has been established, this opportunistic pathogen is difficult to eradicate. This paper demonstrates that the A. baumannii biofilm-associated protein (Bap) is necessary for mature biofilm formation on medically relevant surfaces, including polypropylene, polystyrene, and titanium. Scanning electron microscopy analyses of biofilms show that Bap is required for three-dimensional tower structure and water channel formation. In conjunction with persistence on abiotic surfaces, adherence to eukaryotic cells is an important step in bacterial colonization resulting in infection of the host. We have described Bap as the surface structure involved in adherence of A. baumannii to both normal human bronchial epithelial cells and normal human neonatal keratinocytes. However, Bap is not involved in internalization of the bacterium in these two cell lines. Furthermore, this study shows that the presence of Bap increases the bacterial cell surface hydrophobicity. The results of this study are pertinent, as the data lead to a better understanding of the role of Bap in biofilm formation on medical surfaces and in colonization of the host. PMID- 22083704 TI - Protection of piglets against Edema disease by maternal immunization with Stx2e toxoid. AB - Edema disease (ED) in piglets is caused by Shiga toxin Stx2e-producing Escherichia coli. We show that a genetically disarmed Stx2e toxoid is a safe antigen that generates antiserum protecting piglets against the Stx2e toxin. Immunization of suckling piglets with the Stx2e toxoid was safe, had no adverse effects on growth of the piglets, and resulted in effective prevention of edema disease clinical symptoms after challenge with the Stx2e toxin. Our data showed that maternal immunity against the Stx2e toxoid can be transmitted from the vaccinated sows to the piglets via the colostrum. Very high levels of Stx2e specific serum antibodies persisted in these piglets until 1 month postweaning, bridging the critical period in which the weaned piglets are most susceptible to edema infection. Challenge with Stx2e toxin resulted in clinical signs of edema disease and death of all control piglets from nonimmunized sows, whereas none of the piglets from immunized sows developed clinical signs of ED. PMID- 22083705 TI - Entamoeba histolytica induces intestinal cathelicidins but is resistant to cathelicidin-mediated killing. AB - The enteric protozoan parasite Entamoeba histolytica is the cause of potentially fatal amebic colitis and liver abscesses. E. histolytica trophozoites colonize the colon, where they induce inflammation, penetrate the mucosa, and disrupt the host immune system. The early establishment of E. histolytica in the colon occurs in the presence of antimicrobial human (LL-37) and murine (CRAMP [cathelin related antimicrobial peptide]) cathelicidins, essential components of the mammalian innate defense system in the intestine. Studying this early step in the pathogenesis of amebic colitis, we demonstrate that E. histolytica trophozoites or their released proteinases, including cysteine proteinase 1 (EhCP1), induce intestinal cathelicidins in human intestinal epithelial cell lines and in a mouse model of amebic colitis. Despite induction, E. histolytica trophozoites were found to be resistant to killing by these antimicrobial peptides, and LL-37 and CRAMP were rapidly cleaved by released amebic cysteine proteases. The cathelicidin fragments however, did maintain their antimicrobial activity against bacteria. Degradation of intestinal cathelicidins is a novel function of E. histolytica cysteine proteinases in the evasion of the innate immune system in the bowel. Thus, early intestinal epithelial colonization of invasive trophozoites involves a complex interplay in which the ultimate outcome of infection depends in part on the balance between degradation of cathelicidins by amebic released cysteine proteinases and upregulation of proinflammatory mediators which trigger the inflammatory response. PMID- 22083706 TI - Immunobiotic Lactobacillus jensenii elicits anti-inflammatory activity in porcine intestinal epithelial cells by modulating negative regulators of the Toll-like receptor signaling pathway. AB - The effect of Lactobacillus jensenii TL2937 on the inflammatory immune response triggered by enterotoxigenic Escherichia coli (ETEC) and lipopolysaccharide (LPS) in a porcine intestinal epitheliocyte cell line (PIE cells) was evaluated. Challenges with ETEC or LPS elicited Toll-like receptor 4 (TLR4)-mediated inflammatory responses in cultured PIE cells, indicating that our cell line may be useful for studying inflammation in the guts of weaning piglets. In addition, we demonstrated that L. jensenii TL2937 attenuated the expression of proinflammatory cytokines and chemokines caused by ETEC or LPS challenge by downregulating TLR4-dependent nuclear factorkappaB (NF-kappaB) and mitogen activated protein kinase (MAPK) activation. Furthermore, we demonstrated that L. jensenii TL2937 stimulation of PIE cells upregulated three negative regulators of TLRs: A20, Bcl-3, and MKP-1, deepening the understanding of an immunobiotic mechanism of action. L. jensenii TL2937-mediated induction of negative regulators of TLRs would have a substantial physiological impact on homeostasis in PIE cells, because excessive TLR inflammatory signaling would be downregulated. These results indicated that PIE cells can be used to study the mechanisms involved in the protective activity of immunobiotics against intestinal inflammatory damage and may provide useful information for the development of new immunologically functional feeds that help to prevent inflammatory intestinal disorders, including weaning-associated intestinal inflammation. PMID- 22083707 TI - Mitogen-activated protein kinase-dependent interleukin-1alpha intracrine signaling is modulated by YopP during Yersinia enterocolitica infection. AB - Yersinia enterocolitica is a food-borne pathogen that preferentially infects the Peyer's patches and mesenteric lymph nodes, causing an acute inflammatory reaction. Even though Y. enterocolitica induces a robust inflammatory response during infection, the bacterium has evolved a number of virulence factors to limit the extent of this response. We previously demonstrated that interleukin 1alpha (IL-1alpha) was critical for the induction of gut inflammation characteristic of Y. enterocolitica infection. More recently, the known actions of IL-1alpha are becoming more complex because IL-1alpha can function both as a proinflammatory cytokine and as a nuclear factor. In this study, we tested the ability of Y. enterocolitica to modulate intracellular IL-1alpha-dependent IL-8 production in epithelial cells. Nuclear translocation of pre-IL-1alpha protein and IL-1alpha-dependent secretion of IL-8 into the culture supernatant were increased during infection with a strain lacking the 70-kDa virulence plasmid compared to the case during infection with the wild type, suggesting that Yersinia outer proteins (Yops) might be involved in modulating intracellular IL 1alpha signaling. Infection of HeLa cells with a strain lacking the yopP gene resulted in increased nuclear translocation of pre-IL-1alpha and IL-1alpha dependent secretion of IL-8 similar to what is observed with bacteria lacking the virulence plasmid. YopP is a protein acetylase that inhibits mitogen-activated protein kinase (MAP kinase)- and NF-kappaB-dependent signal transduction pathways. Nuclear translocation of pre-IL-1alpha and IL-1alpha-dependent secretion of IL-8 in response to Yersinia enterocolitica infection were dependent on extracellular signal-regulated kinase (ERK) and p38 MAP kinase signaling but independent of NF-kappaB. These data suggest that Y. enterocolitica inhibits intracellular pre-IL-1alpha signaling and subsequent proinflammatory responses through inhibition of MAP kinase pathways. PMID- 22083708 TI - Tissue barriers of the human placenta to infection with Toxoplasma gondii. AB - Toxoplasma gondii is a ubiquitous, obligate intracellular parasite capable of crossing the placenta to cause spontaneous abortion, preterm labor, or significant disease in the surviving neonate. Exploration of the cellular and histological components of the placental barrier is in its infancy, and both how and where T. gondii breaches it are unknown. The human placenta presents two anatomical interfaces between maternal cells and fetal cells (trophoblasts): (i) the villous region where maternal blood bathes syncytialized trophoblasts for nutrient exchange and (ii) the maternal decidua, where mononuclear, extravillous trophoblasts anchor the villous region to the uterus. Using first-trimester human placental explants, we demonstrate that the latter site is significantly more vulnerable to infection, despite presenting a vastly smaller surface. This is consistent with past findings concerning two vertically transmitted viruses and one bacterium. We further explore whether three genetically distinct T. gondii types (I, II, and III) are capable of preferential placental infection and survival in this model. We find no difference in these strains' ability to infect placental explants; however, slightly slower growth is evident in type II (Prugniaud [Pru]) parasites relative to other cell types, although this did not quite achieve statistical significance. PMID- 22083709 TI - Disruption of the phospholipase D gene attenuates the virulence of Aspergillus fumigatus. AB - Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In this study, disruption of the pld gene encoding phospholipase D (PLD), an important member of the phospholipase protein family in A. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity of A. fumigatus. The pld gene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization of A. fumigatus into A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 MUM phosphatidic acid, the PLD product. Indeed, complementation of pld restored the PLD activity and internalization capacity of A. fumigatus. Phagocytosis of A. fumigatus conidia by J774 macrophages was not affected by the absence of the pld gene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization of A. fumigatus into A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of the pld gene attenuated the virulence of A. fumigatus in mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD of A. fumigatus regulates its internalization into lung epithelial cells and may represent an important virulence factor for A. fumigatus infection. PMID- 22083710 TI - The repeat-in-toxin family member TosA mediates adherence of uropathogenic Escherichia coli and survival during bacteremia. AB - Uropathogenic Escherichia coli (UPEC) is responsible for the majority of uncomplicated urinary tract infections (UTI) and represents the most common bacterial infection in adults. UPEC utilizes a wide range of virulence factors to colonize the host, including the novel repeat-in-toxin (RTX) protein TosA, which is specifically expressed in the host urinary tract and contributes significantly to the virulence and survival of UPEC. tosA, found in strains within the B2 phylogenetic subgroup of E. coli, serves as a marker for strains that also contain a large number of well-characterized UPEC virulence factors. The presence of tosA in an E. coli isolate predicts successful colonization of the murine model of ascending UTI, regardless of the source of the isolate. Here, a detailed analysis of the function of tosA revealed that this gene is transcriptionally linked to genes encoding a conserved type 1 secretion system similar to other RTX family members. TosA localized to the cell surface and was found to mediate (i) adherence to host cells derived from the upper urinary tract and (ii) survival in disseminated infections and (iii) to enhance lethality during sepsis (as assessed in two different animal models of infection). An experimental vaccine, using purified TosA, protected vaccinated animals against urosepsis. From this work, it was concluded that TosA belongs to a novel group of RTX proteins that mediate adherence and host damage during UTI and urosepsis and could be a novel target for the development of therapeutics to treat ascending UTIs. PMID- 22083711 TI - Pathoadaptive conditional regulation of the type VI secretion system in Vibrio cholerae O1 strains. AB - The most recently discovered secretion pathway in gram-negative bacteria, the type VI secretion system (T6SS), is present in many species and is considered important for the survival of non-O1 non-O139 Vibrio cholerae in aquatic environments. Until now, it was not known whether there is a functionally active T6SS in wild-type V. cholerae O1 strains, the cause of cholera disease in humans. Here, we demonstrate the presence of a functionally active T6SS in wild-type V. cholerae O1 strains, as evidenced by the secretion of the T6SS substrate Hcp, which required several gene products encoded within the putative vas gene cluster. Our analyses showed that the T6SS of wild-type V. cholerae O1 strain A1552 was functionally activated when the bacteria were grown under high osmolarity conditions. The T6SS was also active when the bacteria were grown under low temperature (23 degrees C), suggesting that the system may be important for the survival of the bacterium in the environment. A test of the interbacterial virulence of V. cholerae strain A1552 against an Escherichia coli K-12 strain showed that it was strongly enhanced under high osmolarity and that it depended on the hcp genes. Interestingly, we found that the newly recognized osmoregulatory protein OscR plays a role in the regulation of T6SS gene expression and secretion of Hcp from V. cholerae O1 strains. PMID- 22083712 TI - Infection of mice by Salmonella enterica serovar Enteritidis involves additional genes that are absent in the genome of serovar Typhimurium. AB - Salmonella enterica serovar Enteritidis causes a systemic, typhoid-like infection in newly hatched poultry and mice. In the present study, a library of 54,000 transposon mutants of S. Enteritidis phage type 4 (PT4) strain P125109 was screened for mutants deficient in the in vivo colonization of the BALB/c mouse model using a microarray-based negative-selection screening. Mutants in genes known to contribute to systemic infection (e.g., Salmonella pathogenicity island 2 [SPI-2], aro, rfa, rfb, phoP, and phoQ) and enteric infection (e.g., SPI-1 and SPI-5) in this and other Salmonella serovars displayed colonization defects in our assay. In addition, a strong attenuation was observed for mutants in genes and genomic islands that are not present in S. Typhimurium or in most other Salmonella serovars. These genes include a type I restriction/modification system (SEN4290 to SEN4292), the peg fimbrial operon (SEN2144A to SEN2145B), a putative pathogenicity island (SEN1970 to SEN1999), and a type VI secretion system remnant SEN1001, encoding a hypothetical protein containing a lysin motif (LysM) domain associated with peptidoglycan binding. Proliferation defects for mutants in these individual genes and in exemplar genes for each of these clusters were confirmed in competitive infections with wild-type S. Enteritidis. A DeltaSEN1001 mutant was defective for survival within RAW264.7 murine macrophages in vitro. Complementation assays directly linked the SEN1001 gene to phenotypes observed in vivo and in vitro. The genes identified here may perform novel virulence functions not characterized in previous Salmonella models. PMID- 22083714 TI - Oral infection with signature-tagged Listeria monocytogenes reveals organ specific growth and dissemination routes in guinea pigs. AB - Listeria monocytogenes causes a serious food-borne disease due to its ability to spread from the intestine to other organs, a process that is poorly understood. In this study we used 20 signature-tagged wild-type clones of L. monocytogenes in guinea pigs in combination with extensive quantitative data analysis to gain insight into extraintestinal dissemination. We show that L. monocytogenes colonized the liver in all asymptomatic animals. Spread to the liver occurred as early as 4 h after ingestion via a direct pathway from the intestine to the liver. This direct pathway contributed significantly to the bacterial load in the liver and was followed by a second wave of dissemination via the mesenteric lymph nodes (indirect pathway). Furthermore, bacteria were eliminated in the liver, whereas small intestinal villi provided a niche for bacterial replication, indicating organ-specific differences in net bacterial growth. Bacteria were shed back from intestinal villi into the small intestinal lumen and reinfected the Peyer's patches. Together, these results support a novel dissemination model where L. monocytogenes replicates in intestinal villi, is shed into the lumen, and reinfects intestinal immune cells that traffic to liver and mesenteric lymph nodes, a process that occurs even during asymptomatic colonization. PMID- 22083713 TI - The Neisseria meningitidis ZnuD zinc receptor contributes to interactions with epithelial cells and supports heme utilization when expressed in Escherichia coli. AB - Neisseria meningitidis employs redundant heme acquisition mechanisms, including TonB receptor-dependent and receptor-independent uptakes. The TonB-dependent zinc receptor ZnuD shares significant sequence similarity to HumA, a heme receptor of Moraxella catarrhalis, and contains conserved motifs found in many heme utilization proteins. We present data showing that, when expressed in Escherichia coli, ZnuD allowed heme capture on the cell surface and supported the heme dependent growth of an E. coli hemA strain. Heme agarose captured ZnuD in enriched outer membrane fractions, and this binding was inhibited by excess free heme, supporting ZnuD's specific interaction with heme. However, no heme utilization defect was detected in the meningococcal znuD mutant, likely due to unknown redundant TonB-independent heme uptake mechanisms. Meningococcal replication within epithelial cells requires a functional TonB, and we found that both the znuD and tonB mutants were defective not only in survival within epithelial cells but also in adherence to and invasion of epithelial cells. Ectopic complementation rescued these phenotypes. Interestingly, while znuD expression was repressed by Zur with zinc as a cofactor, it also was induced by iron in a Zur-independent manner. A specific interaction of meningococcal Fur protein with the znuD promoter was demonstrated by electrophoretic mobility shift assay (EMSA). Thus, the meningococcal ZnuD receptor likely participates in both zinc and heme acquisition, is regulated by both Zur and Fur, and is important for meningococcal interaction with epithelial cells. PMID- 22083715 TI - The Vsa shield of Mycoplasma pulmonis is antiphagocytic. AB - The infection of mice with Mycoplasma pulmonis is a model for studying chronic mycoplasmal respiratory disease. Many in vivo and in vitro studies have used the organism to gain a better understanding of host-pathogen interactions in chronic respiratory infection. The organism's Vsa proteins contain an extensive tandem repeat region. The length of the tandem repeat unit varies from as few as 11 amino acids to as many as 19. The number of tandem repeats can be as high as 60. The number of repeats varies at a high frequency due to slipped-strand mispairing events that occur during DNA replication. When the number of repeats is high, e.g., 40, the mycoplasma is resistant to lysis by complement but does not form a robust biofilm. When the number of repeats is low, e.g., 5, the mycoplasma is killed by complement when the cells are dispersed but has the capacity to form a biofilm that resists complement. Here, we examine the role of the Vsa proteins in the avoidance of phagocytosis and find that cells producing a protein with many tandem repeats are relatively resistant to killing by macrophages. These results may be pertinent to understanding the functions of similar proteins that have extensive repeat regions in other microbes. PMID- 22083716 TI - Fusion of HSA influences TNF-alpha neutralizing activity of shTNFRs. AB - Soluble human tumor necrosis factor receptors (shTNFRI and shTNFRII) are antagonists of tumor necrosis factor-alpha (TNF-alpha) and are under clinical investigation as therapy for autoimmune diseases and transplant rejection. However, shTNFRI and shTNFRII are limited for clinical usage because of their short half-lives in vivo. Recombinant TNF-alpha receptors (infliximab and etanercept) are used in treatment of rheumatoid arthritis and Crohn's disease but are also being tested for a number of other autoimmune diseases. Human serum albumin (HSA) has been used to construct long-acting fusion proteins. Here, we report the effect of fusion of HSA with shTNFRI and with shTNFRII on shTNFR's neutralizing activity against TNF-alpha. HSA fusion proteins were separately expressed in Pichia pastoris. Purified recombinant shTNFRI-HSA, HSA-shTNFRI and HSA-shTNFRII could block the cytolytic activity of TNF-alpha in L929 cells, and the fusion at N-terminus of shTNFRI could result in larger degree of activity decline than that at the C-terminus. Activity of three fusion proteins was much weaker than etanercept, which demonstrated that fusion of HSA significantly influenced TNF-alpha neutralizing activity of shTNFRs. Compared with Fc fragment, HSA fusion technology may therefore not be an ideal strategy in development of long-acting shTNFRs protein drugs. PMID- 22083717 TI - Small RNA RyhB as a potential tool used for metabolic engineering in Escherichia coli. AB - Small RNA (RyhB) was overexpressed artificially using an arabinose-inducible system in Escherichia coli and resulted in more succinate (7-fold) accumulation, which suggested that RyhB had a strong effect on sdhCDAB genes. Acetate was also increased indicating that RyhB had a comprehensive influence on glucose central metabolism. RyhB might therefore be useful for metabolic engineering of E. coli. PMID- 22083718 TI - Virus-binding activity of the truncated C subunit of porcine aminopeptidase N expressed in Escherichia coli. AB - Seven overlapping truncated forms of the C subunit of porcine aminopeptidase N (pAPN-C) were expressed in Escherichia coli. By western blotting and ELISA test, all recombinant proteins were recognized by the antibody against native porcine aminopeptidase N. Recombinant proteins, rpAPN-C2 (aa 623-722) and rpAPN-C3 (aa 673-772), had the highest binding activity with swine transmissible gastroenteritis virus among the truncated pAPN-C recombinant proteins. The overlapping region (aa 673-722) between rpAPN-C2 and rpAPN-C3 is indicated to play a key role in viral binding. PMID- 22083719 TI - Ultrahigh field systems and applications at 7 T and beyond: progress, pitfalls, and potential. AB - About 150 researchers around the world convened at the Chateau Lake Louise on February 20-23, 2011 to present and discuss the latest research in human and animal imaging and spectroscopy at field strengths of 7 T or above (termed ultrahigh field) at the third ISMRM-sponsored high field workshop. The clear overall message from the workshop presentations and discussion is that ultrahigh field imaging is gaining momentum with regard to new clinically relevant findings, anatomic and functional MRI results, susceptibility contrast advancements, solutions to high field-related image quality challenges, and to generally push the limits of resolution and speed of high field imaging. This meeting report is organized in a manner reflecting the meeting organization itself, covering the seven sessions that were approximately titled: (1) high field overview from head to body to spectroscopy; (2) susceptibility imaging; (3) proffered session on susceptibility, ultrafast imaging, unique contrast at 7 T, and angiography; (4) neuroscience applications; (5) proffered session on coils, shimming, parallel imaging, diffusion tensor imaging, and MRI-PET fusion; (6) high field animal imaging and spectroscopy, as well as a vendor overview, and (7) Cutting edge technology at 7 T. PMID- 22083720 TI - Sexuality in patients undergoing haematopoietic stem cell transplantation. AB - McKee and Schover have suggested that sexuality is an aspect of intimacy that is frequently compromised by cancer and its treatments. Cancer, both in terms of diagnosis and treatments, may have a dramatic impact on both intimacy and sexuality. There is a body of published research addressing sexual concerns among patients with prostatic, testicular, breast, and rectal cancers. This issue seems to be less well documented in patients who have undergone haematopoietic stem cell transplantation (HSCT). In this review, we seek to elaborate different points regarding sexuality and how it is affected in patients undergoing HSCT, with the aim of identifying optimum solutions for such patients in confronting such problems in the course of cancer treatment. PMID- 22083721 TI - Effect of alternating magnetic field treatments on enzymatic parameters of cellulase. AB - BACKGROUND: Cellulase is an enzyme of the glycosyl hydrolase family that catalyses the cleavage of beta-1,4 glycosidic bonds in cellulose. In this study an alternating magnetic field was applied to evaluate cellulase activity using carboxymethyl cellulose (CMC) as substrate. RESULTS: The maximum and minimum activities of cellulase occurred when magnetic fields of 2.2 and 4.2 mT respectively were applied for 20 min. Following these treatments, the enzymatic parameters K(m) and V(m) were determined based on fitting to the Michaelis-Menten equations. Generally, K(m) showed the opposite trend to V(m) under magnetic field treatments. Treatment of enzyme/substrate solutions at 4.2 mT inhibited enzyme activity whereas treatment at 2.2 mT promoted it. CONCLUSION: It appears that treating enzyme/substrate solutions with different magnetic fields can inhibit or promote enzyme activity. Further research is needed to determine how the magnetic field influences the enzyme and substrate. PMID- 22083722 TI - Atrial natriuretic peptides in Han Wistar, Sprague-Dawley and spontaneously hypertensive rats. AB - The atrial natriuretic peptide (ANP) and its precursor (N-terminal fragment of atrial natriuretic peptide, NT-proANP) are natriuretic peptides released into the circulation as a consequence of an acute atrial stretch. As for the brain natriuretic peptide and its N-terminal fragment, the biological significance of ANP and NT-proANP has been widely studied in humans, but the literature is lacking information about the determination of these biomarkers in veterinary medicine and, in particular, in the toxicological species used in preclinical pharmaceutical drug development. This paper describes the evaluation of ANP and NT-proANP levels in a healthy population of Han Wistar and Sprague-Dawley rats, as well as in a rodent model of hypertension (Spontaneously Hypertensive rats). Both biomarkers were measured by mean of two commercially available enzyme immunoassays and serum levels were correlated with heart weight and histopathological findings in the heart, with the aim of building an integrated assessment of the significance of these biomarkers. Results obtained demonstrated that NT-proANP and ANP can be accurately measured in the different rat strains, with NT-proANP concentrations higher than those of ANP, as expected because of its longer half-life. In addition, both correlated well with cardiac hypertrophy evaluated by means of heart weight and histopathological examination. NT-proANP and ANP represent reliable markers of cardiac hypertrophy in the rat. PMID- 22083723 TI - Pharmaceutical interventions on prescription problems in a Danish pharmacy setting. AB - BACKGROUND: International studies regarding pharmacists' interventions towards prescription problems produce highly variable results. The only peer-reviewed study in a Danish setting estimated an intervention rate of 2.3 per 1,000 prescriptions. With the introduction of a new tool for registration, we hypothesized that a better estimate could be obtained. OBJECTIVE: We aimed to produce an up-to-date estimate of the extent and type of pharmacists' interventions towards prescription problems in a Danish pharmacy setting SETTING: The study was conducted at Copenhagen Sonderbro Pharmacy, a large urban 24-hour pharmacy. METHOD: Data were collected prospectively through an electronic form. All interventions were primarily classified as either clinical or administrative in nature, and further classified in a number of pre-determined subcategories. Furthermore, information about age, sex, time of day, the wording of the prescription, the performed intervention, the person performing the intervention and the type of prescriber were recorded. All entries were manually validated by a study pharmacist. MAIN OUTCOME MEASURE: The intervention rate, given as the number of interventions per 1,000 prescriptions. RESULTS: We found 599 validated interventions. Thirty-two percent of the interventions were clinical and 68% administrative by nature. Fifty-one percent of the administrative and 35% of the clinical interventions were regarding antibiotics. In the study period, a total of 55,522 prescriptions were filled out together with 3,069 dose-dispensing packages, giving a rate of 10.2 (9.4-11.1) interventions per 1,000 prescriptions. CONCLUSION: We found an intervention rate substantially higher than reported in previous Danish studies. PMID- 22083724 TI - Diabetes knowledge, medication adherence and glycemic control among patients with type 2 diabetes. AB - BACKGROUND: Most of interventions that have attempted to improve medication adherence in type 2 diabetes have been educational; on the assumption that knowledge regarding diabetes might affect patients' adherence to their treatment regimen. OBJECTIVES: The purpose of the study was to investigate any association of knowledge and medication adherence with glycemic control in patients with type 2 diabetes mellitus. Setting The study was conducted at the Diabetes Outpatients Clinic, Hospital Pulau Penang. METHODS: A cross-sectional study was conducted with a convenience sample of 540 adult patients with type 2 diabetes attending the clinic. A questionnaire including previously validated Michigan Diabetes Knowledge Test and Morisky Medication Adherence Scale was used and the patients' medical records were reviewed for haemoglobin A1C (HbA1C) levels and other disease-related information. A total of 35 (6.48%) patients were excluded after data collection due to lack of HbA1C results. RESULTS: Five hundred and five patients were included in the final analysis, with a mean age of 58.15 years (SD = 9.16), 50.7% males and median HbA1C of 7.6 (IQR was 6.7-8.9). The median total knowledge score was 7.0 (IQR was 5.0-10.0) while the median adherence score was 6.5 (IQR was 4.75-7.75). Significant correlations were found between the three variables (HbA1C, knowledge and adherence). A significantly higher score for knowledge and adherence (P < 0.05) was found in those patients with lower HbA1C. Higher diabetes knowledge, higher medication adherence and using mono-therapy were significant predictors of good glycemic control in the multivariate analysis. CONCLUSION: Patients' knowledge about diabetes is associated with better medication adherence and better glycemic control. In addition to other factors affecting medication adherence and glycemic control, healthcare providers should pay attention to knowledge about diabetes that the patients carry towards medication adherence. PMID- 22083725 TI - Octreotide-modified N-octyl-O, N-carboxymethyl chitosan micelles as potential carriers for targeted antitumor drug delivery. AB - Octreotide (OCT) was recently found to have high binding affinity to the positive tumor cells of somatostatin receptors (SSTRs). In this study, octreotide-Phe polyethylene glycol-stearic acid was first successfully synthesized and used as a targeting molecule for N-octyl-O, N-carboxymethyl chitosan (OCC). Doxorubicin (DOX) was loaded into OCT-modified OCC micelles (DOX-OCC-OCT). The drug-loaded micelles obtained exhibited spherical shape, small particle sizes, and negative zeta potentials. The cytotoxicity of DOX-OCC-OCT micelles against MCF-7 cells (SSTRs expressing) was found to significantly increase with the increased amount of OCT modification, whereas no significant difference was observed against WI-38 cells (no SSTRs expressing). Results of flow cytometry, fluorescence microscopy, and confocal laser scanning microscopy confirmed that DOX-OCC-OCT micelles could remarkably increase the uptake of DOX in MCF-7 cells. All the results indicated that OCC-OCT micelles may be a promising intracellular targeting carrier for efficient delivery of antitumor drugs into tumor cells. PMID- 22083726 TI - Lentiviral-mediated RNAi knockdown yields a novel mouse model for studying Cyp2b function. AB - There are few in vivo knockout models available to study the function of Cyp2 members involved in the metabolism of endogenous and exogenous chemicals. These models may help provide insight into the cytochrome P450s (CYPs) responsible for the detoxification and activation of drugs, environmental toxicants, and endobiotics. The aim of this work is to produce a potent Cyp2b-knockdown (KD) mouse for subsequent study of Cyp2b function. We made a quintuple Cyp2b-KD mouse using lentiviral-promoted short hairpin RNA (shRNA) homologous to all five murine Cyp2b subfamily members (Cyp2b9, 2b10, 2b13, 2b19, and 2b23). The Cyp2b-KD mice are viable, fertile, and without obvious gross abnormalities except for an increase in liver weight. Expression of the three hepatic Cyp2b members, 2b9, 2b10, and 2b13, is significantly repressed as demonstrated by quantitative real time PCR and Western blotting. The constitutive androstane receptor activator, 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), was used to determine if shRNA-mediated Cyp2b10 repression could be outcompeted by Cyp2b10 induction. TCPOBOP-treated Cyp2b-KD mice show 80-90% less Cyp2b protein expression than TCPOBOP-treated wild-type (WT) mice, demonstrating that Cyp induction does not outcompete the repressive function of the shRNA. Untreated and TCPOBOP-treated Cyp2b-KD mice are poor metabolizers of parathion compared with WT mice. Furthermore, Cyp2b-KD mice are sensitive to parathion, an organophosphate insecticide primarily metabolized by Cyp2b enzymes, when compared with WT mice. In summary, we designed an shRNA construct that repressed the expression and activity of multiple Cyp2b enzymes. We foresee that this novel Cyp2b-KD mouse model will significantly improve our understanding of the role of Cyp2b enzymes in chemical sensitivity and drug metabolism. PMID- 22083727 TI - Understanding ciliated epithelia: the power of Xenopus. AB - Ciliated epithelia are important in a wide variety of biological contexts where they generate directed fluid flow. Here we address the fundamental advances in understanding ciliated epithelia that have been achieved using Xenopus as a model system. Xenopus embryos are covered with a ciliated epithelium that propels fluid unidirectionally across their surface. The external nature of this tissue, coupled with the molecular tools available in Xenopus and the ease of microscopic analysis on intact animals has thrust Xenopus to the forefront of ciliated epithelia biology. We discuss advances in understanding the molecular regulators of ciliated epithelia cell fate as well as basic aspects of ciliated epithelia cell biology including ciliogenesis and cell polarity. PMID- 22083728 TI - De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. AB - A small number of rare, recurrent genomic copy number variants (CNVs) are known to substantially increase susceptibility to schizophrenia. As a consequence of the low fecundity in people with schizophrenia and other neurodevelopmental phenotypes to which these CNVs contribute, CNVs with large effects on risk are likely to be rapidly removed from the population by natural selection. Accordingly, such CNVs must frequently occur as recurrent de novo mutations. In a sample of 662 schizophrenia proband-parent trios, we found that rare de novo CNV mutations were significantly more frequent in cases (5.1% all cases, 5.5% family history negative) compared with 2.2% among 2623 controls, confirming the involvement of de novo CNVs in the pathogenesis of schizophrenia. Eight de novo CNVs occurred at four known schizophrenia loci (3q29, 15q11.2, 15q13.3 and 16p11.2). De novo CNVs of known pathogenic significance in other genomic disorders were also observed, including deletion at the TAR (thrombocytopenia absent radius) region on 1q21.1 and duplication at the WBS (Williams-Beuren syndrome) region at 7q11.23. Multiple de novos spanned genes encoding members of the DLG (discs large) family of membrane-associated guanylate kinases (MAGUKs) that are components of the postsynaptic density (PSD). Two de novos also affected EHMT1, a histone methyl transferase known to directly regulate DLG family members. Using a systems biology approach and merging novel CNV and proteomics data sets, systematic analysis of synaptic protein complexes showed that, compared with control CNVs, case de novos were significantly enriched for the PSD proteome (P=1.72 * 10-6. This was largely explained by enrichment for members of the N-methyl-D-aspartate receptor (NMDAR) (P=4.24 * 10-6) and neuronal activity regulated cytoskeleton-associated protein (ARC) (P=3.78 * 10-8) postsynaptic signalling complexes. In an analysis of 18 492 subjects (7907 cases and 10 585 controls), case CNVs were enriched for members of the NMDAR complex (P=0.0015) but not ARC (P=0.14). Our data indicate that defects in NMDAR postsynaptic signalling and, possibly, ARC complexes, which are known to be important in synaptic plasticity and cognition, play a significant role in the pathogenesis of schizophrenia. PMID- 22083730 TI - Replication of association between a SLITRK1 haplotype and Tourette Syndrome in a large sample of families. PMID- 22083729 TI - Pharmacogenetics in psychiatry: translating research into clinical practice. AB - Pharmacogenetic/pharmacogenomic (PGx) approaches to psychopharmacology aim to identify clinically meaningful predictors of drug efficacy and/or side-effect burden. To date, however, PGx studies in psychiatry have not yielded compelling results, and clinical utilization of PGx testing in psychiatry is extremely limited. In this review, the authors provide a brief overview on the status of PGx studies in psychiatry, review the commercialization process for PGx tests and then discuss methodological considerations that may enhance the potential for clinically applicable PGx tests in psychiatry. The authors focus on design considerations that include increased ascertainment of subjects in the earliest phases of illness, discuss the advantages of drug-induced adverse events as phenotypes for examination and emphasize the importance of maximizing adherence to treatment in pharmacogenetic studies. Finally, the authors discuss unique aspects of pharmacogenetic studies that may distinguish them from studies of other complex traits. Taken together, these data provide insights into the design and methodological considerations that may enhance the potential for clinical utility of PGx studies. PMID- 22083731 TI - Genetic modulation of neural response during working memory in healthy individuals: interaction of glucocorticoid receptor and dopaminergic genes. AB - Suboptimal performance in working memory (WM) tasks and inefficient prefrontal cortex functioning are related to dysregulation of dopaminergic (DA) and hypothalamic-pituitary-adrenal systems. The aim of the present study was to investigate the joint effect of genetic polymorphisms coding for DA catabolism and glucocorticoid receptor (GR, NR3C1) on brain functioning. The study group (90 right-handed white Caucasian healthy individuals) underwent functional magnetic resonance imaging experiments to examine blood oxygenation level dependent (BOLD) response during a WM task with varying cognitive load (1-, 2- and 3-back). We have also examined skin conductance response (SCR) during the WM task and resting state cerebral blood flow with continuous arterial spin labelling. The genetic markers of interest included Catechol-O-Methyl-Transferase (COMT) (Met(158)Val) and NR3C1 single-nucleotide polymorphisms (BclI C/G rs41423247, 9beta A/G rs6198 and rs1866388 A/G). Haplotype-based analyses showed (i) a significant effect of COMT polymorphism on left anterior cingulate cortex, with greater deactivation in Met carriers than in Val/Val homozygotes; (ii) a significant effect of BclI polymorphism on right dorsolateral prefrontal cortex (DLPFC), with greater activation in G/G carriers than in C carriers and (iii) an interactive effect of BclI (G/G) and COMT (Met/Met) polymorphisms, which was associated with greater activation in right DLPFC. These effects remained significant after controlling for whole-brain resting-state blood flow. SCR amplitude was positively correlated with right DLPFC activation during WM. This study demonstrated that GR and COMT markers exert their separate, as well as interactive, effects on DLPFC function. Epistasis of COMT and BclI minor alleles is associated with higher activation, suggesting lower efficiency, of DLPFC during WM. PMID- 22083732 TI - Synthesis of polyester nanoparticles in miniemulsion obtained by radical ring opening of BMDO and their potential as biodegradable drug carriers. AB - 5,6-Benzo-2-methylene-1,3-dioxepane (BMDO) is used to obtain degradable polymeric nanoparticles via a statistical free-radical copolymerization with MMA and styrene in direct miniemulsion. The nanoparticles are analyzed by means of IR, NMR, DLS, SEM, and TEM. They show excellent cellular uptake and drug delivery properties. The cellular uptake into HeLa cells of particles resulting from copolymerization of BMDO with styrene is drastically enhanced compared to pure polystyrene. As a model drug system, paclitaxel is incorporated in PBMDO particles and its release and the effect on HeLa cells is studied and compared to commercial drug formulations. It is found that a drug delivery system based on PBMDO shows an excellent pharmacological effect. PMID- 22083733 TI - In silico implementation of synthetic gene networks. AB - Computational synthetic biology has borrowed methods, concepts, and techniques from systems biology and electrical engineering. Features of tools for the analysis of biochemical networks and the design of electric circuits have been combined to develop new software, where Standard Biological Parts (physically stored at the MIT Registry) have a mathematical description, based on mass action or Hill kinetics, and can be assembled into genetic networks in a visual, "drag & drop" fashion. Recent tools provide the user with databases, simulation environments, formal languages, and even algorithms for circuit automatic design to refine and speed up gene network construction. Moreover, advances in automation of DNA assembly indicate that synthetic biology software soon will drive the wet-lab implementation of DNA sequences. PMID- 22083734 TI - Standardization in synthetic biology. AB - Synthetic Biology is founded on the idea that complex biological systems are built most effectively when the task is divided in abstracted layers and all required components are readily available and well-described. This requires interdisciplinary collaboration at several levels and a common understanding of the functioning of each component. Standardization of the physical composition and the description of each part is required as well as a controlled vocabulary to aid design and ensure interoperability. Here, we describe standardization initiatives from several disciplines, which can contribute to Synthetic Biology. We provide examples of the concerted standardization efforts of the BioBricks Foundation comprising the request for comments (RFC) and the Registry of Standardized Biological parts as well as the international Genetically Engineered Machine (iGEM) competition. PMID- 22083735 TI - Robust optimal design of synthetic biological networks. AB - In engineering, the use of mathematical modeling for design purposes has a long history. Long before any technical realization, a system is planned, simulated, and tested extensively on the computer. In biosciences, however, the application of model-based design before going to the wet lab is still rather rare but has particularly high potential in synthetic biology. We demonstrate exemplarily how mathematical modeling and numerical optimization can be used for the design of a circadian rhythm that is supposed to oscillate robustly with respect to uncertainty in system parameters. PMID- 22083736 TI - Predicting synthetic gene networks. AB - Synthetic biology aims at designing and building new biological functions in living organisms. The complexity of cellular regulation (regulatory, metabolic, and signaling interactions, and their coordinated action) can be tackled via the development of quantitative mathematical models. These models are useful to test biological hypotheses and observations, and to predict the possible behaviors of a synthetic network. Indeed, synthetic biology uses such models to design synthetic networks, prior to their construction in the cell, to perform specific tasks, or to change a biological process in a desired way. The synthetic network is built by assembling biological "parts" taken from different systems; therefore it is fundamental to identify, isolate, and test regulatory motifs which occur frequently in biological pathways. In this chapter, we describe how to model and predict the behavior of synthetic networks in two difference cases: (1) a synthetic network composed of five genes regulating each other through a variety of regulatory interactions in the yeast Saccharomyces cerevisiae (2) a synthetic transcriptional positive feedback loop stably integrated in Human Embryonic Kidney 293 cells (HEK293). PMID- 22083737 TI - Reprogramming a GFP reporter gene subjects it to complex lentiviral gene regulation. AB - Late human immunodeficiency virus (HIV)-derived RNAs encoding relevant therapeutic targets or promising vaccine compounds, such as the HIV-1 group specific antigen (Gag), are translocated from the nucleus into the cytoplasm via sophisticated export machinery. Relevant steps include the concerted action of several cis-acting RNA elements with the viral Rev-shuttle protein and several cellular components (Ran1/Exportin; Crm1). Based on detailed understanding of the molecular mechanisms guiding this complex process, we used rational codon usage modification to design and reprogram a GFP encoding reporter RNA now exactly mimicking the complex transcriptional and posttranscriptional regulation of late lentiviral mRNAs. PMID- 22083738 TI - A high-throughput microfluidic method for generating and characterizing transcription factor mutant libraries. AB - Characterizing libraries of mutant proteins is a challenging task, but can lead to detailed functional insights on a specific protein, and general insights for families of proteins such as transcription factors. Challenges in mutant protein screening consist in synthesizing the necessary expression-ready DNA constructs and transforming them into a suitable host for protein expression. Protein purification and characterization are also non-trivial tasks that are not easily scalable to hundreds or thousands of protein variants. Here we describe a method based on a high-throughput microfluidic platform to screen and characterize the binding profile of hundreds of transcription factor variants. DNA constructs are synthesized by a rapid two-step PCR approach without the need of cloning or transformation steps. All transcription factor mutants are expressed on-chip followed by characterization of their binding specificities against 64 different DNA target sequences. The current microfluidic platform can synthesize and characterize up to 2,400 protein-DNA pairs in parallel. The platform method is also generally applicable, allowing high-throughput functional studies of proteins. PMID- 22083739 TI - Identifying and optimizing intracellular protein-protein interactions using bacterial genetic selection. AB - Protein-protein interactions are crucial for the vast majority of biological processes. To fully understand these processes therefore requires methods for identifying protein interactions within the complex cellular environment. To isolate interacting proteins, we have developed a simple and reliable genetic selection by exploiting the inbuilt "hitchhiker" mechanism of the Escherichia coli twin-arginine translocation (Tat) pathway. This method is based on the unique ability of the Tat system to efficiently co-localize noncovalent complexes of two folded polypeptides to the periplasmic space of E. coli. The genetic selection is comprised of two engineered fusion proteins: an N-terminal Tat signal peptide fused to the protein of interest, and the known or putative partner protein fused to mature TEM-1 beta-lactamase. The efficiency with which co-localized beta-lactamase chimeras are exported in the periplasm, and thus confer ampicillin resistance to cells, is directly linked to the relative binding affinity of the protein-ligand system. Thus, ampicillin resistance can be used as a convenient readout for identifying and optimizing protein interactions in E. coli. Furthermore, because Tat substrates must be correctly folded for export, our method favors the identification of soluble, non-aggregating, protease resistant protein pairs. Overall, we anticipate that this new selection tool will be useful for discovering and engineering protein drugs, protein complexes for structural biology, factors that inhibit PPIs, and components for synthetic biology. PMID- 22083740 TI - Zinc-finger nucleases-based genome engineering to generate isogenic human cell lines. AB - Customized zinc-finger nucleases (ZFNs) have developed into a promising technology to precisely alter mammalian genomes for biomedical research, biotechnology, or human gene therapy. In the context of synthetic biology, the targeted integration of a transgene or reporter cassette into a "neutral site" of the human genome, such as the AAVS1 locus, permits the generation of isogenic human cell lines with two major advantages over standard genetic manipulation techniques: minimal integration site-dependent effects on the transgene and, vice versa, no functional perturbation of the host-cell transcriptome. Here we describe in detail how ZFNs can be employed to target integration of a transgene cassette into the AAVS1 locus and how to characterize the targeted cells by PCR based genotyping. PMID- 22083741 TI - RNA-based networks: using RNA aptamers and ribozymes as synthetic genetic devices. AB - Within the last few years, a set of synthetic riboswitches has been engineered, which expands the toolbox of genetic regulatory devices. Small molecule binding aptamers have been used for the design of such riboswitches by insertion into untranslated regions of mRNAs, exploiting the fact that upon ligand binding the RNA structure interferes either with translation initiation or pre-mRNA splicing in yeast. In combination with self-cleaving ribozymes, aptamers have been used to modulate RNA stability. In this chapter, we discuss the applicability of different aptamers, ways to identify novel genetic devices, the pros and cons of various insertion sites and the application of allosteric ribozymes. Our expertise help to apply synthetic riboswitches to engineer complex genetic circuits. PMID- 22083742 TI - MicroRNA circuits for transcriptional logic. AB - One of the longstanding challenges in synthetic biology is rational design of complex regulatory circuitry with multiple biological inputs, complex internal processing, and physiologically active outputs. We have previously proposed how to address this challenge in the case of transcription factor inputs. Here we describe the methods used to construct these synthetic circuits, capable of performing logic integration of transcription factor inputs using microRNA expression vectors and RNA interference (RNAi). The circuits operate in mammalian cells and they can serve as starting point for more complex synthetic information processing networks in these cells. PMID- 22083743 TI - Light-regulated gene expression in yeast. AB - An important basic requirement of synthetic genetic networks is the option of external control of gene expression. Although several chemically inducible systems are available, all of these suffer from the common problem: the chemical inducers are difficult to remove so that to terminate the response. We have described a regulatory expression system for yeast, which employs light as inducer. This light switch translates light-controlled protein-protein interactions into the transcription of selected genes in a dose-dependent and reversible manner. PMID- 22083744 TI - Light-controlled gene switches in mammalian cells. AB - Remote control of cells is a desirable feature in synthetic biology. We established a light-switchable interfering peptide (iPEP) which controls gene expression by modulating the activity of a transcription factor. For photo switching, the iPEP is cross-linked with a cis-trans isomerizable cross-linker in such a way that the light-activated cis form enables inhibitor folding rendering it active, whereas the dark-adapted trans form forces the inhibitor into an inactive form. Switching can be repeated in both directions. The iPEP acts as dominant-negative inhibitor targeting c-Jun and c-Fos of the transcription factor activator protein-1 (AP-1). Light-activated peptides exhibited much stronger inhibition of AP-1:DNA complexes and interference with gene transcription than their nonactivated counter parts. In this chapter, we provide protocols for cross linking, peptide purification, observation of structural changes upon photo switching, DNA binding analyses as well as gene expression studies in mammalian cells. PMID- 22083745 TI - Expressed protein modifications: making synthetic proteins. AB - Techniques to manipulate cellular gene expression such that amino acid analogs not encoded by the genetic code are incorporated into a polypeptide chain have recently gained increasing interest. The so-called noncanonical amino acids often have unusual properties that can be translated into target proteins by reprogrammed ribosomal protein synthesis. Residue-specific substitution of a specific canonical amino acid by its analogs provokes global effects in the resulting protein congeners that include improved stability or catalytic activity, reduced redox sensitivity, as well as altered spectral properties. Thus, the approach holds great promise for the engineering of synthetic proteins.This contribution describes a protocol for the incorporation of a noncanonical amino acid into a target protein expressed in an appropriate amino acid auxotrophic E. coli strain. PMID- 22083746 TI - Using transcription machinery engineering to elicit complex cellular phenotypes. AB - Cellular hosts are widely used for the production of chemical compounds, including pharmaceutics, fuels, and specialty chemicals. However, common metabolic engineering techniques are limited in their capacity to elicit multigenic, complex phenotypes. These phenotypes can include non-pathway-based traits, such as tolerance and productivity. Global transcription machinery engineering (gTME) is a generic methodology for eliciting these complex cellular phenotypes. In gTME, dominant mutant alleles of a transcription-related protein are screened for their ability to reprogram cellular metabolism and regulation, resulting in a unique and desired phenotype. gTME has been successfully applied to both prokaryotic and eukaryotic systems, resulting in improved environmental tolerances, metabolite production, and substrate utilization. The underlying principle involves creating mutant libraries of transcription factors, screening for a desired phenotype, and iterating the process in a directed evolution fashion. The successes of this approach and details for its implementation and application are described here. PMID- 22083747 TI - Streamlining of a Pseudomonas putida genome using a combinatorial deletion method based on minitransposon insertion and the Flp-FRT recombination system. AB - Here, we document a technique to reduce the size of the genome of Pseudomonas putida by using a combinatorial mini-Tn5-targeted Flp-FRT recombination system. This method combines random insertions with the site-specific Flp-FRT recombination system to generate successive random deletions in a single strain in which parts of the genome are excised via the action of the cognate flippase. For this purpose, we have generated two mini-Tn5 transposon mutant libraries with single and double integrations of either mini-Tn5 KpF alone or mini-Tn5 KpF in parallel with mini-Tn5 TF, respectively. These mini-Tn5 transposons carry different selectable markers and each has an FRT (Flippase Recognition Target) site. Mapping of the position of both mini-Tn5 transposons in the chromosome of P. putida was conducted by Arbitrary Primed-PCR (AP-PCR). Subsequent sequencing of the PCR fragments led to the identification of the coordinates of the transposons and the orientation of both FRT sites. Under specific laboratory conditions, both FRT sites were recognized by the flippase, and the deletion of a nonessential intervening genomic segment along with the transposon backbones occurred without inheritance of any marker genes. PMID- 22083748 TI - Transposon-based and plasmid-based genetic tools for editing genomes of gram negative bacteria. AB - A good part of the contemporary synthetic biology agenda aims at reprogramming microorganisms to enhance existing functions and/or perform new tasks. Moreover, the functioning of complex regulatory networks, or even a single gene, is revealed only when perturbations are entered in the corresponding dynamic systems and the outcome monitored. These endeavors rely on the availability of genetic tools to successfully modify a la carte the chromosome of target bacteria. Key aspects to this end include the removal of undesired genomic segments, systems for the production of directed mutants and allelic replacements, random mutant libraries to discover new functions, and means to stably implant larger genetic networks into the genome of specific hosts. The list of gram-negative species that are appealing for such genetic refactoring operations is growingly expanding. However, the repertoire of available molecular techniques to do so is very limited beyond Escherichia coli. In this chapter, utilization of novel tools is described (exemplified in two plasmids systems: pBAM1 and pEMG) tailored for facilitating chromosomal engineering procedures in a wide variety of gram negative microorganisms. PMID- 22083749 TI - Synthetic networks: oscillators and toggle switches for Escherichia coli. AB - Bacterial synthetic gene networks are constructed by manipulating the regulation of genes inside a cell, with the purpose of eliciting novel regulatory behaviors. The methods for manipulating genes and gene regulation in E. coli are well established, making it the preferred host for basic studies of synthetic networks. We focus our work on constructing two kinds of synthetic gene networks: toggle switches (bistable systems) and oscillators. Toggle switches are capable of exhibiting two stable steady states of gene expression (OFF and ON) without stable intermediate states; the steady state reached by the system depends on the previous history of the system. Biological oscillators exhibit regular cycles in gene expression around an unstable steady state. Studying these two kinds of synthetic networks helps advance our understanding of natural bistable systems and oscillators, such as the circadian oscillators controlling gene expression in many types of cells, and the genetic systems controlling the cell cycle and differentiation in metazoans. PMID- 22083750 TI - Studying microbial communities in biofilms. AB - Most microorganisms in nature subsist as heterogeneous surface-associated communities called biofilms. In biofilms members of one or more microbial species live together for multiple generations, and this allows them to cooperate and co adapt. The ability to reliably manipulate, characterize, and engineer microbial biofilms will enable controlled studies of ecosystem dynamics and unprecedented design opportunities for biological sensors and actuators. Biofilms can be grown in the laboratory, and spatial structure, gene expression, and productivity (total biomass accumulation) can be observed and quantified as a function of time using confocal laser scanning microscopy. This chapter details the materials and methods necessary to grow and study engineered microbial communities in biofilms. PMID- 22083751 TI - Quantitative analysis of the spatiotemporal dynamics of a synthetic predator-prey ecosystem. AB - A major focus in synthetic biology is the rational design and implementation of gene circuits to control dynamics of individual cells and, increasingly, cellular populations. Population-level control is highlighted in recent studies which attempt to design and implement synthetic ecosystems (or engineered microbial consortia). On the one hand, these engineered systems may serve as a critical technological foundation for practical applications. On the other hand, they may serve as well-defined model systems to examine biological questions of broad relevance. Here, using a synthetic predator-prey ecosystem as an example, we illustrate the basic experimental techniques involved in system implementation and characterization. By extension, these techniques are applicable to the analysis of other microbial-based synthetic or natural ecosystems. PMID- 22083752 TI - Drosophila S2 Schneider cells: a useful tool for rebuilding and redesigning approaches in synthetic biology. AB - Synthetic biology is an engineering approach to biology. A synthetic biologist wants to describe biological molecules and their subdomains as well-defined parts of a molecular machine. To achieve this goal, synthetic biologists rebuild minimal functional biological systems from well-defined parts or they design new molecules that do not exist in nature but have new and useful functions. In short, these engineering approaches can be summarized as "rebuild, alter, and understand." The Drosophila S2 Schneider cell is a useful tool for both rebuilding and redesigning approaches. S2 cells are phagocytic cells that easily take up large amounts of DNA from the cell culture. They, thus, have a high cotransfection rate, allowing the coexpression of up to 12 different proteins. We have developed a transient transfection protocol allowing the rapid and parallel analysis of wild-type and altered forms of a biological system. This chapter describes our methods to rebuild and better understand mammalian signaling systems in the evolutionary distant environment of Drosophila S2 cells. PMID- 22083753 TI - Synthetic gene networks in plant systems. AB - Synthetic biology methods are routinely applied in the plant field as in other eukaryotic model systems. Several synthetic components have been developed in plants and an increasing number of studies report on the assembly into functional synthetic genetic circuits. This chapter gives an overview of the existing plant genetic networks and describes in detail the application of two systems for inducible gene expression. The ethanol-inducible system relies on the ethanol responsive interaction of the AlcA transcriptional activator and the AlcR receptor resulting in the transcription of the gene of interest (GOI). In comparison, the translational fusion of GOI and the glucocorticoid receptor (GR) domain leads to the dexamethasone-dependent nuclear translocation of the GOI::GR protein. This chapter contains detailed protocols for the application of both systems in the model plants potato and Arabidopsis, respectively. PMID- 22083755 TI - Synthetic gene networks as blueprint for smart hydrogels. AB - The rapidly emerging ability to design and construct synthetic gene networks in mammalian cells is based on the availability of mutually compatible genetic switches that enable the time-dependent induction of transgene expression in response to the dose of an externally applied stimulus. As these genetic switches are inherently compatible with mammalian cell physiology, they are as well predestined to control the functionality of cell-free synthetic devices within an overall physiologic background. In this chapter, we describe how a genetic switch that was originally designed for gene therapeutic studies can be applied in materials science to design and construct a biohybrid hydrogel that can be used to release a therapeutic growth factor in response to an externally applied stimulus for controlling cell fate and function in a time- and space-resolved manner. PMID- 22083754 TI - Design and construction of synthetic gene networks in mammalian cells. AB - Advances in the development of molecular tools for the inducible control of transcription, translation, and protein degradation are the basis for the rapidly emerging design and construction of synthetic gene networks in mammalian cells.In this chapter, we describe such tools and how they can be integrated into a synthetic gene network with desired functionality. The network design and construction process is illustrated in the form of a detailed protocol for the implementation of a logic NOR gate based on an inducible promoter combined with an inducible protein degradation system. PMID- 22083756 TI - Antibacterial potential of hGlyrichin encoded by a human gene. AB - Emerging multidrug-resistant (MDR) bacteria are an enormous threat to human life because of their resistance to currently available antibiotics. The genes encoding antibacterial peptides have been studied extensively and are excellent candidates for a new generation of antibiotic drugs to fight MDR bacteria. In contrast to traditional antibiotics, antibacterial peptides, which do not cause drug resistance, have an unparalleled advantage. However, because most antibacterial peptides originate in species other than humans, the hetero immunological rejection of antibacterial peptides is a key disadvantage that limits their clinical application. In this study, we identify hGlyrichin as a potential human antibacterial polypeptide. The hGlyrichin polypeptide kills a variety of bacteria including the MDR bacteria methicillin-resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa, and MDR tubercle bacillus. A 19 amino acid peptide (pCM19) at positions 42-60 of hGlyrichin is crucial for its antibacterial activity. The hGlyrichin polypeptide kills bacteria through the destruction of the bacterial membrane. In addition, all peptides that are homologous to hGlyrichin have antibacterial activity and can penetrate the bacterial membrane. Importantly, hGlyrichin does not cause hemolytic side effects in vitro or in vivo. Therefore, based on the virtues of hGlyrichin, i.e., the absence of hetero-immunological rejection and hemolytic side effects and the unambiguous efficacy of killing pathogenic MDR bacteria, we propose hGlyrichin as a potential human antibacterial polypeptide. PMID- 22083757 TI - Successful treatment of anaplastic meningioma metastatic to cervical lymph nodes. AB - BACKGROUND: Cervical lymph node metastases of meningioma represent an important diagnostic and treatment challenge. Not only has this entity been rarely described, but successful treatment has never been reported in the literature. METHODS AND RESULTS: This case report was conducted using reviews of the literature. A 58-year-old man with a history of resected anaplastic meningioma was referred for a right neck mass. Excisional biopsy revealed metastatic meningioma, and a metastatic workup was negative. Modified radical neck dissection showed positivity in 5 lymph nodes. The patient received adjuvant intensity-modulated radiation therapy (IMRT), for a mean target dose of 60 Gray (Gy). Two years after treatment, the patient was disease free. Eleven cases of cervical lymph node metastasis of meningioma were identified in our literature search, and none described successful treatment of this entity. CONCLUSION: Cervical lymph node metastasis of anaplastic meningioma is potentially treatable with surgical resection and IMRT, although further studies with long-term follow up are necessary. PMID- 22083758 TI - The influence of field strength on the apparent diffusion coefficient of 3He gas in human lungs. AB - The (3)He MR diffusion signal is sensitive to lung microstructure, but it is also affected by the presence of background field inhomogeneities induced by the magnetic susceptibility difference at the air-tissue interface. These susceptibility-induced gradients, which are dependent on field strength, have been assumed negligible in theoretical models used to extract airway morphometric information from (3)He MR diffusion data at field strengths up to 4.7 T. In this work, the effect of susceptibility gradients on (3)He apparent diffusion coefficient is demonstrated with experiments in healthy volunteers at two B(0) field strengths: 1.5 and 3 T. Apparent diffusion coefficient values obtained at 3 T were systematically larger than at 1.5 T, demonstrating that susceptibility effects are statistically significant even at clinical field strengths (B(0) <= 3 T) and introduce biases in the estimates of airway dimensions (e.g., mean linear intercept up to 17% larger at 3 T than 1.5 T). Susceptibility effects should be taken into account in the development of theoretical models of lung (3)He MR diffusion and considered when interpreting (3)He apparent diffusion coefficients obtained at different B(0). PMID- 22083759 TI - High-temperature dielectric response of ferroelectric relaxors. AB - It has long been considered that polar nanoregions in relaxors form at Burns temperature T(d) ~ 600K. High-temperature dielectric investigations of Pb(Mg(1/3)Nb(2/3)) O(3) (PMN) single crystal, PMN-PbTiO(3) ceramics, and (Pb,La) (Zr,Ti)O(3) ceramics reveal, however, that dielectric dispersion, detected around 600K, is due to the Maxwell-Wagner-type contributions of surface layers. The intrinsic response was analyzed in terms of the universal scaling, taking into account the asymptotic and the correction-to-scaling behavior, and the results imply much higher T(d) or formation of polar nanoregions in a broad temperature range. High values of the dielectric constant indicate, however, that polar order already exists at the highest measured temperatures of 800K. The obtained critical exponents indicate critical behavior associated with universality classes typically found in spin glasses. PMID- 22083760 TI - Terahertz dielectric response of ferroelectric Ba(x)Sr(1-x)TiO3 thin films. AB - Terahertz time-domain spectroscopy has been used to investigate the dielectric and optical properties of ferroelectric Ba(x)Sr(1-x)TiO(3) thin films for nominal x-values of 0.4, 0.6, and 0.8 in the frequency range of 0.3 to 2.5 THz. The ferroelectric thin films were deposited at approximately 700 nm thickness on [001] MgO substrate by pulsed laser deposition. The measured complex dielectric and optical constants were compared with the Cole-Cole relaxation model. The results show that the Cole-Cole relaxation model fits well with the data throughout the frequency range and the dielectric relaxation behavior of ferroelectric Ba(x)Sr(1-x)TiO(3) thin films varies with the films compositions. Among the compositions of Ba(x)Sr(1-x)TiO(3) films with different Ba/Sr ratios, Ba(0.6)Sr(0.4)TiO(3) has the highest dielectric constants and the shortest dielectric relaxation time. PMID- 22083761 TI - 80-MHz intravascular ultrasound transducer using PMN-PT free-standing film. AB - [Pb(Mg(1/3)Nb(2/3))O(3)](0.63)[PbTiO(3)](0.37) (PMN-PT) free-standing film of comparable piezoelectric properties to bulk material with thickness of 30 MUm has been fabricated using a modified precursor coating approach. At 1 kHz, the dielectric permittivity and loss were 4364 and 0.033, respectively. The remnant polarization and coercive field were 28 MUC/cm(2) and 18.43 kV/cm. The electromechanical coupling coefficient k(t) was measured to be 0.55, which was close to that of bulk PMN-PT single-crystal material. Based on this film, high frequency (82 MHz) miniature ultrasonic transducers were fabricated with 65% bandwidth and 23 dB insertion loss. Axial and lateral resolutions were determined to be as high as 35 and 176 MUm. In vitro intravascular imaging on healthy rabbit aorta was performed using the thin film transducers. In comparison with a 35-MHz IVUS transducer, the 80-MHz transducer showed superior resolution and contrast with satisfactory penetration depth. The imaging results suggest that PMN-PT free standing thin film technology is a feasible and efficient way to fabricate very high-frequency ultrasonic transducers. PMID- 22083762 TI - Miniaturized acceleration sensors with in-plane polarized piezoelectric thin films produced by micromachining. AB - Miniaturized acceleration sensors employing piezoelectric thin films were fabricated through batch micromachining with silicon and silicon-on-insulator (SOI) wafers. The acceleration sensors comprised multiple suspension beams supporting a central seismic mass. Ferroelectric (Pb,La)(Zr,Ti) O(3) (PLZT) thin films were coated and in-plane polarized on the surfaces of the suspension beams for realizing electromechanical conversion through the piezoelectric effect. Interdigital electrodes were formed on the PLZT films and connected in parallel. Finite element analyses were conducted for the stress and strain distributions, providing guidance to the structural design, including optimizing electrode positioning for collecting the electrical output constructively. Uniformity of the beam thickness and sample consistency were significantly improved by using SOI wafers instead of silicon wafers. The measurement results showed that all the sensor samples had fundamental resonances of symmetric out-of-plane vibration mode at frequencies in the range of 8 to 35 kHz, depending on the sample dimensions. These sensors exhibited stable electrical outputs in response to acceleration input, achieving a high signal-to-noise ratio without any external amplifier or signal conditioning. PMID- 22083763 TI - Oscillator frequency stability improvement by means of negative feedback. AB - A novel, simple method is proposed to increase the frequency stability of an oscillator. An additional negative feedback is used in combination with the positive loop of the harmonic oscillator to decrease the phase sensitivity to fluctuations of parameters other than the resonator. The main advantage of the proposed correction approach is that it does not require expensive external elements such as mixers or resonators. The validity of the method is theoretically demonstrated on a Colpitts oscillator using the control system theory approach and numerical simulations, and is experimentally verified with phase noise measurements of an actual oscillator-mockup. It is shown that the medium-term frequency stability can be easily improved by a factor of ten. PMID- 22083764 TI - Assessment of viscous and elastic properties of sub-wavelength layered soft tissues using shear wave spectroscopy: theoretical framework and in vitro experimental validation. AB - In elastography, quantitative imaging of soft tissue elastic properties is provided by local shear wave speed estimation. Shear wave imaging in a homogeneous medium thicker than the shear wavelength is eased by a simple relationship between shear wave speed and local shear modulus. In thin layered organs, the shear wave is guided and thus undergoes dispersive effects. This case is encountered in medical applications such as elastography of skin layers, corneas, or arterial walls. In this work, we proposed and validated shear wave spectroscopy as a method for elastic modulus quantification in such layered tissues. Shear wave dispersion curves in thin layers were obtained by finite difference simulations and numerical solving of the boundary conditions. In addition, an analytical approximation of the dispersion equation was derived from the leaky Lamb wave theory. In vitro dispersion curves obtained from phantoms were consistent with numerical studies (deviation <1.4%). The least-mean-squares fitting of the dispersion curves enables a quantitative and accurate (error < 5% of the transverse speed) assessment of the elasticity. Dispersion curves were also found to be poorly influenced by shear viscosity. This phenomenon allows independent recovery of the shear modulus and the viscosity, using, respectively, the dispersion curve and the attenuation estimation along the propagation axis. PMID- 22083765 TI - Dual-pulse frequency compounded superharmonic imaging. AB - Tissue second-harmonic imaging is currently the default mode in commercial diagnostic ultrasound systems. A new modality, superharmonic imaging (SHI), combines the third through fifth harmonics originating from nonlinear wave propagation through tissue. SHI could further improve the resolution and quality of echographic images. The superharmonics have gaps between the harmonics because the transducer has a limited bandwidth of about 70% to 80%. This causes ghost reflection artifacts in the superharmonic echo image. In this work, a new dual pulse frequency compounding (DPFC) method to eliminate these artifacts is introduced. In the DPFC SHI method, each trace is constructed by summing two firings with slightly different center frequencies. The feasibility of the method was established using a single-element transducer. Its acoustic field was modeled in KZK simulations and compared with the corresponding measurements obtained with a hydrophone apparatus. Subsequently, the method was implemented on and optimized for a setup consisting of an interleaved phased-array transducer (44 elements at 1 MHz and 44 elements at 3.7 MHz, optimized for echocardiography) and a programmable ultrasound system. DPFC SHI effectively suppresses the ghost reflection artifacts associated with imaging using multiple harmonics. Moreover, compared with the single-pulse third harmonic, DPFC SHI improved the axial resolution by 3.1 and 1.6 times at the -6-dB and -20-dB levels, respectively. Hence, DPFC offers the possibility of generating harmonic images of a higher quality at a cost of a moderate frame rate reduction. PMID- 22083766 TI - Time-delay spectrometry measurement of magnitude and phase of hydrophone response. AB - A method based on time-delay spectrometry (TDS) was developed for measuring both magnitude and phase response of a hydrophone. The method was tested on several types of hydrophones used in medical ultrasound exposimetry over the range from 5 to 18 MHz. These included polyvinylidene fluoride (PVDF) spot-poled membrane, needle, and capsule designs. One needle hydrophone was designed for high intensity focused ultrasound (HIFU) applications. The average reproducibility (after repositioning the hydrophone) of the phase measurement was 2.4 degrees . The minimum-phase model, which implies that the phase response is equal to the inverse Hilbert transform of the natural logarithm of the magnitude response, was tested with TDS hydrophone data. Direct TDS-based measurements of hydrophone phase responses agreed well with calculations based on the minimum-phase model, with rms differences of 1.76 degrees (PVDF spot-poled membrane hydrophone), 3.10 degrees (PVDF capsule hydrophone), 3.43 degrees (PVDF needle hydrophone), and 3.36 degrees (ceramic needle hydrophone) over the range from 5 to 18 MHz. Therefore, phase responses for several types of hydrophones may be inferred from measurements of their magnitude responses. Calculation of phase response based on magnitude response using the minimumphase model is a relatively simple and practical alternative to direct measurement of phase. PMID- 22083768 TI - A restoration framework for ultrasonic tissue characterization. AB - Ultrasonic tissue characterization has become an area of intensive research. This procedure generally relies on the analysis of the unprocessed echo signal. Because the ultrasound echo is degraded by the non-ideal system point spread function, a deconvolution step could be employed to provide an estimate of the tissue response that could then be exploited for a more accurate characterization. In medical ultrasound, deconvolution is commonly used to increase diagnostic reliability of ultrasound images by improving their contrast and resolution. Most successful algorithms address deconvolution in a maximum a posteriori estimation framework; this typically leads to the solution of l(2) norm or (1)-norm constrained optimization problems, depending on the choice of the prior distribution. Although these techniques are sufficient to obtain relevant image visual quality improvements, the obtained reflectivity estimates are, however, not appropriate for classification purposes. In this context, we introduce in this paper a maximum a posteriori deconvolution framework expressly derived to improve tissue characterization. The algorithm overcomes limitations associated with standard techniques by using a nonstandard prior model for the tissue response. We present an evaluation of the algorithm performance using both computer simulations and tissue-mimicking phantoms. These studies reveal increased accuracy in the characterization of media with different properties. A comparison with state-of-the-art Wiener and l(1)-norm deconvolution techniques attests to the superiority of the proposed algorithm. PMID- 22083767 TI - Lesion generation through ribs using histotripsy therapy without aberration correction. AB - This study investigates the feasibility of using high-intensity pulsed therapeutic ultrasound, or histotripsy, to non-invasively generate lesions through the ribs. Histotripsy therapy mechanically ablates tissue through the generation of a cavitation bubble cloud, which occurs when the focal pressure exceeds a certain threshold. We hypothesize that histotripsy can generate precise lesions through the ribs without aberration correction if the main lobe retains its shape and exceeds the cavitation initiation threshold and the secondary lobes remain below the threshold. To test this hypothesis, a 750-kHz focused transducer was used to generate lesions in tissue-mimicking phantoms with and without the presence of rib aberrators. In all cases, 8000 pulses with 16 to 18 MPa peak rarefactional pressure at a repetition frequency of 100 Hz were applied without aberration correction. Despite the high secondary lobes introduced by the aberrators, high-speed imaging showed that bubble clouds were generated exclusively at the focus, resulting in well-confined lesions with comparable dimensions. Collateral damage from secondary lobes was negligible, caused by single bubbles that failed to form a cloud. These results support our hypothesis, suggesting that histotripsy has a high tolerance for aberrated fields and can generate confined focal lesions through rib obstacles without aberration correction. PMID- 22083770 TI - Analysis of interaction between two SAW modes in Pt grating on langasite cut (0 degrees , 138.5 degrees , 26.6 degrees ). AB - The numerical technique based on a previously developed rational approximation of harmonic admittance of a periodic grating was applied to analysis of SAW behavior in platinum grating on langasite cut with Euler angles (0 degrees , 138.5 degrees , 26.6 degrees ). The approximation is able to take into account interaction between surface and bulk waves or between two SAW modes. SAW dispersion was calculated at different values of electrode thickness varying between 1% and 4% of wavelength. It was found that with increasing Pt thickness, SAW behavior in the grating is strongly affected by interaction between two SAW modes propagating in the same orientation. An additional stopband, which results from this interaction, occurs at certain detuning from synchronous reflection condition and can cause spurious resonances of the admittance function. Interaction between two SAW modes is also responsible for anomalously slow growth of reflectivity with increasing platinum thickness. PMID- 22083769 TI - Use of smoothing splines for analysis of backscattered ultrasonic waveforms: application to monitoring of steroid treatment of dystrophic mice. AB - Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by progressive weakness and wasting of skeletal and cardiac muscle; boys present with weakness by the age of 5 years and, if left untreated, are unable to walk without assistance by the age of 10 years. Therapy for DMD has been primarily palliative, with oral steroids emerging as a first-line approach even though this treatment has serious side-effects. Consequently, low-cost imaging technology suitable for improved diagnosis and treatment monitoring of DMD would be of great value, especially in remote and underserved areas. Previously, we reported use of the logarithm of the signal energy, log [E(f)], and a new method for ultrasound signal characterization using entropy, H(f), to monitor prednisolone treatment of skeletal muscle in a dystrophin-deficient mouse model. Three groups were studied: mdx mice treated with prednisolone, a control group of mdx mice treated with saline, and a control group of wild-type mice treated with saline. It was found that both log [E(f)] and H(f) were required to statistically differentiate the three groups. In the current study, we show that preprocessing of the raw ultrasound using optimal smoothing splines before computation of either log [E(f)] or a rapidly computable variant of Hf, denoted I(f,infinity), permits delineation of all three groups by either metric alone. This opens the way to the ultimate goal of this study, which is identification and implementation of new diagnostically sensitive algorithms on the new generation of low-cost hand-held clinical ultrasonic imaging systems. PMID- 22083771 TI - Revisited mode-expansion method for elastic strips. AB - The mode-expansion method is widely applied in waveguide analysis. Particular applications usually include only a few modes to obtain explicit analytical results for simple waveguides. Here, we apply the method to the evaluation of the dynamic properties of elastic strips; to obtain useful results for thin strips, tens of plate modes must be involved in the expansion, representing the vibration shape of the strip. Although this increases the numerical complexity of the analysis, it is still easy for both numerical implementation and for physical interpretation of results. The final result we seek in this paper is the matrix of harmonic impedance of strips that provides dependence of displacements on both upper and lower sides of a strip of rectangular cross-section on arbitrary traction applied to these sides, where both the traction and displacements are expressed in the spatial Fourier series (other sides of strips are assumed to be stress-free). Detailed discussion of numerical issues is provided for isotropic strips and example applications are presented for strips interacting with surface waves or with other strips arranged in a "woodpile" super-lattice. PMID- 22083772 TI - Maximization of the effective impulse delivered by a high-frequency/low-frequency planetary drill tool. AB - Ultrasonic tools are used for a variety of cutting applications in surgery and the food industry, but when they are applied to harder materials, such as rock, their cutting performance declines because of the low effective impulse delivered by each vibration cycle. To overcome this problem, a technique known as high frequency/low-frequency (or alternatively, ultrasonic/sonic) drilling is employed. In this approach, an ultrasonic step-horn is used to deliver an impulse to a free mass which subsequently moves toward a drilling bit, delivering the impulse on contact. The free mass then rebounds to complete the cycle. The horn has time between impacts to build significant vibration amplitude and thus delivers a much larger impulse to the free mass than could be delivered if it were applied directly to the target. To maximize the impulse delivered to the target by the cutting bit, both the momentum transfer from the ultrasonic horn to the free mass and the dynamics of the horn/free mass/cutting bit stack must be optimized. This paper uses finite element techniques to optimize the ultrasonic horns and numerical propagation of the stack dynamics to maximize the delivered effective impulse, validated in both cases by extensive experimental analysis. PMID- 22083773 TI - A cylindrical traveling wave ultrasonic motor using a circumferential composite transducer. AB - This paper intends to present and verify a new idea for constructing traveling wave ultrasonic motors that may effectively avoid the drawbacks of conventional traveling wave motors using bonded PZT plates as the exciting elements. In the configuration of the motor's stator, a composite sandwich type transducer is used to excite a traveling wave in a cylinder with two cantilevers as the coupling bridges between the transducer and the cylinder. The design process of the stator is described using the FEM modal analysis method, and the establishment of traveling wave on the cylindrical stator was simulated by FEM transient analysis. To verify the theoretical analysis results, a laser Doppler scanner was employed to test the mode shapes of a prototype stator excited by the longitudinal and bending vibrations respectively. Finally, to validate the design idea, a prototype motor was fabricated and tested; the typical output features are no load speed of 156 rpm and maximum torque of 0.75 N.m under exciting voltages of 70 V(rms) applied to excite the longitudinal vibration of the transducer and 200 V(rms) applied to excite the bending vibration. PMID- 22083774 TI - Fast direct solution of 3-D scattering problems via nonuniform grid-based matrix compression. AB - A fast non-iterative algorithm for the solution of large 3-D acoustic scattering problems is presented. The proposed approach can be used in conjunction with the conventional boundary element discretization of the integral equations of acoustic scattering. The algorithm involves domain decomposition and uses the nonuniform grid (NG) approach for the initial compression of the interactions between each subdomain and the rest of the scatterer. These interactions, represented by the off-diagonal blocks of the boundary element method matrix, are then further compressed while constructing sets of interacting and local basis and testing functions. The compressed matrix is obtained by eliminating the local degrees of freedom through the Schur's complement-based technique procedure applied to the diagonal blocks. In the solution process, the interacting unknowns are first determined by solving the compressed system equations. Subsequently, the local degrees of freedom are determined for each subdomain. The proposed technique effectively reduces the oversampling typically needed when using low order discretization techniques and provides significant computational savings. PMID- 22083775 TI - Membrane hydrophone phase characteristics through nonlinear acoustics measurements. AB - This work considers the need for both the amplitude and phase to fully characterize polyvinylidene fluoride (PVDF) membrane hydrophones and presents a comprehensive discussion of the nonlinear acoustic measurements utilized to extract the phase information and the experimental results taken with two widely used PVDF membrane hydrophones up to 100 MHz. A semi-empirical computer model utilized the hyperbolic propagation operator to predict the nonlinear pressure field and provide the complex frequency response of the corresponding source transducer. The PVDF hydrophone phase characteristics, which were obtained directly from the difference between the computer-modeled nonlinear field simulation and the corresponding measured harmonic frequency phase values, agree to within 10% with the phase predictions obtained from receive-transfer-function simulations based on software modeling of the membrane's physical properties. Cable loading effects and membrane hydrophone resonances were distinguished and identified through a series of impedance measurements and receive transfer function simulations on the hydrophones including their hard-wired coaxial cables. The results obtained indicate that the PVDF membrane hydrophone's phase versus frequency plot exhibits oscillations about a monotonically decreasing line. The maxima and minima inflection point slopes occur at the membrane thickness resonances and antiresonances, respectively. A cable resonance was seen at 100 MHz for the hydrophone with a 1-m cable attached, but not seen for the hydrophone with a shorter 0.65-m cable. PMID- 22083776 TI - ZnO-based FBAR resonators with carbon nanotube electrodes. AB - Film bulk acoustic resonator (FBAR) devices with carbon nanotube (CNT) electrodes directly grown on a ZnO film by thermal chemical vapor deposition have been fabricated. CNT electrodes possess a very low density and high acoustic impedance, which reduces the intrinsic mass loading effect resulting from the electrodes? weight and better confines the longitudinal acoustic standing waves inside the resonator, in turn providing a resonator with a higher quality factor. The influence of the CNTs on the frequency response of the FBAR devices was studied by comparing two identical sets of devices; one set comprised FBARs fabricated with chromium/ gold bilayer electrodes, and the second set comprised FBARs fabricated with CNT electrodes. It was found that the CNTs had a significant effect on attenuating traveling waves at the surface of the FBARs' membranes because of their high elastic stiffness. Three-dimensional finite element analysis of the devices fabricated was carried out, and the numerical simulations were consistent with the experimental results obtained. PMID- 22083777 TI - A hybrid method for calibrating acoustic arrays. AB - A method to calibrate the elements of large arrays devoted to underwater applications is presented. The goal is to measure the sensitivity and directivity of the elements over their full bandwidth. The main constraint comes from the bounded geometry of the experimental setups that limits the duration of the time windows available for analyzing the received signals. Using a short wideband pulse is detrimental to obtaining high signal-to-noise ratios. A classical method for handling this problem is time-delay spectrometry (TDS), which is based on the transmission of a linear frequency- modulated signal combined with a sliding frequency filter. An alternative, hybrid method based on the transmission of a sequence of time-frequency-limited signals is proposed. This hybrid method is shown to provide the same spectral density as TDS in the frequency scanning, but the filtering process is quite different. The transmitted signals are designed to take advantage of the coherent sums of the received signals to track the time of flight of the direct paths between the source and the elements. In addition, a fitting process based on the calibration geometry of data acquisition enables the boundaries of the interference-free time windows to be precisely delineated. An example of the application is described. PMID- 22083778 TI - Modeling of surface acoustic wave strain sensors using coupling-of-modes analysis. AB - SAW devices may be configured as strain sensors, providing passive, wireless strain measurement in demanding conditions. A key consideration is the modeling of the sensors, enabling different device designs to be considered. This paper presents a simulation scheme using coupling-of-modes (COM) analysis which allows both the frequency response of a SAW strain sensor and its bias sensitivity to be evaluated. Example applications are presented to demonstrate the use of the model. PMID- 22083779 TI - Determination of mass density, dielectric, elastic, and piezoelectric constants of bulk GaN crystal. AB - Mass density, dielectric, elastic, and piezoelectric constants of bulk GaN crystal were determined. Mass density was obtained from the measured ratio of mass to volume of a cuboid. The dielectric constants were determined from the measured capacitances of an interdigital transducer (IDT) deposited on a Z-cut plate and from a parallel plate capacitor fabricated from this plate. The elastic and piezoelectric constants were determined by comparing the measured and calculated SAW velocities and electromechanical coupling coefficients on the Z- and X-cut plates. The following new constants were obtained: mass density p = 5986 kg/m(3); relative dielectric constants (at constant strain S) epsilon(S)(11)/epsilon(0) = 8.6 and epsilon(S)(11)/epsilon(0) = 10.5, where epsilon(0) is a dielectric constant of free space; elastic constants (at constant electric field E) C(E)(11) = 349.7, C(E)(12) = 128.1, C(E)(13) = 129.4, C(E)(33) = 430.3, and C(E)(44) = 96.5 GPa; and piezoelectric constants e(33) = 0.84, e(31) = -0.47, and e(15) = -0.41 C/m(2). PMID- 22083780 TI - Deep-collapse operation of capacitive micromachined ultrasonic transducers. AB - Capacitive micromachined ultrasonic transducers (CMUTs) have been introduced as a promising technology for ultrasound imaging and therapeutic ultrasound applications which require high transmitted pressures for increased penetration, high signal-to-noise ratio, and fast heating. However, output power limitation of CMUTs compared with piezoelectrics has been a major drawback. In this work, we show that the output pressure of CMUTs can be significantly increased by deep collapse operation, which utilizes an electrical pulse excitation much higher than the collapse voltage. We extend the analyses made for CMUTs working in the conventional (uncollapsed) region to the collapsed region and experimentally verify the findings. The static deflection profile of a collapsed membrane is calculated by an analytical approach within 0.6% error when compared with static, electromechanical finite element method (FEM) simulations. The electrical and mechanical restoring forces acting on a collapsed membrane are calculated. It is demonstrated that the stored mechanical energy and the electrical energy increase nonlinearly with increasing pulse amplitude if the membrane has a full-coverage top electrode. Utilizing higher restoring and electrical forces in the deep collapsed region, we measure 3.5 MPa peak-to-peak pressure centered at 6.8 MHz with a 106% fractional bandwidth at the surface of the transducer with a collapse voltage of 35 V, when the pulse amplitude is 160 V. The experimental results are verified using transient FEM simulations. PMID- 22083781 TI - Comparison of template-matching and singular-spectrum-analysis methods for imaging implanted brachytherapy seeds. AB - Brachytherapy using small implanted radioactive seeds is becoming an increasingly popular method for treating prostate cancer, in which a radiation oncologist implants seeds in the prostate transperineally under ultrasound guidance. Dosimetry software determines the optimal placement of seeds for achieving the prescribed dose based on ultrasonic determination of the gland boundaries. However, because of prostate movement and distortion during the implantation procedure, some seeds may not be placed in the desired locations; this causes the delivered dose to differ from the prescribed dose. Current ultrasonic imaging methods generally cannot depict the implanted seeds accurately. We are investigating new ultrasonic imaging methods that show promise for enhancing the visibility of seeds and thereby enabling real-time detection and correction of seed-placement errors during the implantation procedure. Real-time correction of seed-placement errors will improve the therapeutic radiation dose delivered to target tissues. In this work, we compare the potential performance of a template matching method and a previously published method based on singular spectrum analysis for imaging seeds. In particular, we evaluated how changes in seed angle and position relative to the ultrasound beam affect seed detection. The conclusion of the present study is that singular spectrum analysis has better sensitivity but template matching is more resistant to false positives; both perform well enough to make seed detection clinically feasible over a relevant range of angles and positions. Combining the information provided by the two methods may further reduce ambiguities in determining where seeds are located. PMID- 22083782 TI - Radially composite piezoelectric ceramic tubular transducer in radial vibration. AB - The radially composite piezoelectric tubular transducer is studied. It is composed of radially poled piezoelectric and a long metal tube. The electro mechanical equivalent circuit of the radially poled piezoelectric and metal tube in radial vibration is obtained. Based on the force and velocity boundary conditions, the six-port electro-mechanical equivalent circuit for the composite tubular transducer is given and the resonance/anti-resonance frequency equations are obtained. The relationship between the resonance frequency and the dimensions is analyzed. Numerically simulated results obtained by the finite element method are compared with those from the analytical method. Composite piezoelectric tubular transducers are designed and manufactured. The resonance/anti-resonance frequencies are measured, and it is shown that the theoretical results are in good agreement with the simulated and experimental results. It is expected that radially composite piezoelectric tubular transducers can be used as high-power ultrasonic radiators in ultrasonic applications, such as ultrasonic liquid processing. PMID- 22083783 TI - Limitations of meta-analyses. PMID- 22083784 TI - The use of glass beads cultivation system to study the global effect of the ppk gene inactivation in Streptomyces lividans. AB - The glass beads cultivation system developed in our laboratory for physiological studies of filamentous microorganisms supports differentiation and allows complete recovery of bacterial colonies and their natural products from cultivation plates. Here, we used this system to study the global effect of ppk gene disruption in Streptomyces lividans. The ppk encoding the enzyme polyphosphate kinase (P) catalyses the reversible polymerisation of gamma phosphate of ATP to polyphosphates. The resulting are phosphate and energy stock polymers. Because P activity impacts the overall energetic state of the cell, it is also connected to secondary metabolite (e.g. antibiotic) biosynthesis. We analysed the global effects of the disruption of this gene including its influence on the production of pigmented antibiotics, on morphological differentiation, on the levels of ATP and on the whole cytoplasmic protein expression pattern of S. lividans. We observed that the S. lividans ppk mutant produced antibiotics earlier and in greater amount than the wild-type (wt) strain. On the other hand, we did not observe any obvious effect on colony morphological development. In agreement with the function of Ppk, we detected much lower levels of ATP in ppk- mutant than in the wt strain. Proteomic analysis revealed that the genes that were influenced by ppk inactivation included enzymes involved in carbon or nitrogen metabolism, phosphate transport and components of the cell translational machinery. We showed that the synthesis of translation elongation factor Tu is during sporulation much higher in ppk- mutant than in wild-type strain. PMID- 22083785 TI - Genetic and virulence characterization of Streptococcus suis type 2 isolates from swine in the provinces of Zhejiang and Henan, China. AB - This study was aimed to examine the genetic characteristics of 44 Streptococcus suis type 2 (SS2) isolates and the virulence attributes of 23 representative isolates. Multilocus sequence typing revealed five sequence types (ST1, ST7, ST28, ST86, and ST162) with 19 isolates assigned to ST7 (43.2%), 14 to ST1 (31.8%), and 9 to ST28 (20.5%). PCR typing of the pilus gene clusters classified the isolates into three types: A (72.7%), B (22.7%), and N (4.5%). All isolates of pilus types A and N were assigned to the ST1 complex containing ST1, ST7, and ST86, while those of type B belonged to the ST27 complex comprising ST28 and ST162. Only two strains had the putative pathogenicity island 89-kb cluster (89K) and were of type N. The type B strains had a significantly lower adhesion, were more readily killed by macrophage, and had lower virulence to mice than those of types A and N. We conclude that SS2 strains of both ST1 and ST27 complexes, parallel to pilus types A and B, were prevalent in the pig populations in Zhejiang Province, and ST7 and ST1 strains were the predominant genotypes in the diseased pigs with pneumonia. PMID- 22083786 TI - A survey on distribution and toxigenicity of Aspergillus flavus from indoor and outdoor hospital environments. AB - In the present study, genetic diversity and mycotoxin profiles of Aspergillus flavus isolated from air (indoors and outdoors), levels (surfaces), and soils of five hospitals in Southwest Iran were examined. From a total of 146 Aspergillus colonies, 63 isolates were finally identified as A. flavus by a combination of colony morphology, microscopic criteria, and mycotoxin profiles. No Aspergillus parasiticus was isolated from examined samples. Chromatographic analyses of A. flavus isolates cultured on yeast extract-sucrose broth by tip culture method showed that approximately 10% and 45% of the isolates were able to produce aflatoxin B(1) (AFB(1)) and cyclopiazonic acid (CPA), respectively. Around 40% of the isolates produced sclerotia on Czapek-Dox agar. The isolates were classified into four chemotypes based on the ability to produce AF and CPA that majority of them (55.5%) belonged to chemotype IV comprising non-mycotoxigenic isolates. Random amplified polymorphic DNA (RAPD) profiles generated by a combination of four selected primers were used to assess genetic relatedness of 16 selected toxigenic and non-toxigenic isolates. The resulting dendrogram demonstrated the formation of two separate clusters for the A. flavus comprised both mycotoxigenic and non-toxigenic isolates in a random distribution. The obtained results in this study showed that RAPD profiling is a promising and efficient tool to determine intra-specific genetic variation among A. flavus populations from hospital environments. A. flavus isolates, either toxigenic or non-toxigenic, should be considered as potential threats for hospitalized patients due to their obvious role in the etiology of nosocomial aspergillosis. PMID- 22083787 TI - Diagnostic properties of three conventional selective plating media for selection of Bacillus cereus, B. thuringiensis and B. weihenstephanensis. AB - The aim of this study was to assess the diagnostic properties of the two selective plating media and a chromogenic medium for identification of Bacillus cereus. The 324 isolates were B. cereus (37%), Bacillus weihenstephanensis (45%) or Bacillus thuringiensis (18%), as identified by a new combination of techniques. All isolates were growing on mannitol-egg yolk-polymyxin agar (MYP), and they did not form acid from mannitol. However, a significant lower number of B. thuringiensis isolates did not show lecithinase activity. All isolates were also growing on polymyxin-egg yolk-mannitol-bromothymol blue agar (PEMBA); however, 11% isolates indicated that they did produce acid from mannitol, and 15% isolates did not show any lecithinase activity. Five of the isolates did not grow at all on the chromogenic agar, and 14 of the growing isolates were beta glucosidase negative. It is concluded that the two recommended selective plating media MYP and PEMBA for detection of B. cereus group bacteria both have their limitations for identification of some B. cereus, B. weihenstephanensis or B. thuringiensis. However, MYP is preferable compared to PEMBA. The chromogenic medium has its own advantages and limitations, and some of the limitations seem to be solved by incubation at 30 degrees C instead of the recommended 37 degrees C. PMID- 22083788 TI - The role of ABC efflux pump, Rv1456c-Rv1457c-Rv1458c, from Mycobacterium tuberculosis clinical isolates in China. AB - Recently the ATP-binding cassette (ABC) efflux pumps have been proved to be a major component of drug resistance in Mycobacterium tuberculosis. The objective of this study was to investigate the expression profiles of Rv1456c-Rv1457c Rv1458c efflux system in clinical isolates of M. tuberculosis and its involvement in drug-resistance mechanisms. Significantly increased mRNA expression of Rv1456c, Rv1457c, and Rv1458c appeared among the clinical isolates (P < 0.05), which are resistant to at least one of the four first-line drugs including rifampin, isoniazid, streptomycin, and ethambutol. In addition, overexpression of this efflux system was more frequently found in multidrug-resistant and extensively drug-resistant M. tuberculosis strains. Therefore, Rv1456c-Rv1457c Rv1458c efflux pumps may play an important role in drug resistance of treatment of M. tuberculosis. Further investigation of this gene may lead to the development of countermeasures against M. tuberculosis drug resistance. PMID- 22083789 TI - Mutational biosynthesis of neomycin analogs by a mutant of neomycin-producing Streptomyces fradiae. AB - Neomycin, produced by Streptomyces fradiae, has been widely used for the treatment of bacterial infections in clinical and agricultural applications. In this study, a neomycin nonproducing mutant of S. fradiae was obtained by gene disruption technique for mutational biosynthesis. A crucial gene neoC (neo7) which encodes 2-deoxystreptamine (2-DOS) synthases was disrupted. The mutant could resume producing neomycin in the presence of 2-DOS. Salen derivatives of 2 DOS were synthesized and individually added to cultures of the mutant. Antibacterial activity of the mutasynthesis products against Staphylococcus aureus and four plant pathogenic bacteria (Pseudomonas solanacarum, Erwinia carotovora, Xanthomonas oryzae, and Xanthomonas campestris) was detected quantitatively by Oxford cup method. It is suggested that all 2-DOS derivatives were incorporated by the mutant into new active neomycin analogs except for 2-DOS derivative 2d ((1R,2r,3S,4R,6S)-4,6-bis((E)-3,5-di-tert-butyl-2 hydroxybenzylideneamino)cyclohexane-1,2,3-triol). Neomycin analogs produced by feeding 2-DOS derivative 2a ((1R,2r,3S,4R,6S)-4,6-bis((E)-2 hydroxybenzylideneamino)cyclohexane-1,2,3-triol) to cultures of the mutant displayed a similar antibacterial activity with neomycin produced by wild strain. PMID- 22083790 TI - BioMart: driving a paradigm change in biological data management. PMID- 22083791 TI - Effects of oligosaccharides on phase transition temperatures and rheological characteristics of waxy rice starch dispersion. AB - BACKGROUND: The creation of starch-based foods incorporated with functional ingredients such as probiotics is of great current interest in the food industry. This study aimed to investigate the effects of prebiotic oligosaccharides on the phase transition temperatures and rheological characteristics of waxy rice starch dispersions. Four oligosaccharides were applied to the rice starch dispersions: chitooligosaccharides, fructooligosaccharides, isomaltooligosaccharides and xylooligosaccharides. RESULTS: The addition of 125 g kg(-1) oligosaccharides elevated the onset and peak temperatures for gelatinisation of 200-400 g kg(-1) waxy rice starch dispersions. The temperature of the storage modulus (G') for gelatinisation increased markedly on adding fructooligosaccharides to 200-300 g kg(-1) waxy rice starch. For gelatinisation of 300 g kg(-1) rice starch dispersion the effectiveness of the oligosaccharides in changing the above parameters was as follows: chitooligosaccharides > fructooligosaccharides > isomaltooligosaccharides > xylooligosaccharides. Moreover, their effectiveness was dependent on the amylose content, as illustrated by comparing waxy and non waxy rice starches (amylose contents 9-256 g kg(-1)). Importantly, the logarithmic G'(95) change was linearly and negatively correlated with amylose content. CONCLUSION: The results suggest that oligosaccharide-containing rice starch dispersions may potentially be used for the formulation of oligosaccharide containing starchy functional foods owing to the rheological changes of these starch dispersions. PMID- 22083792 TI - Forced degradation of therapeutic proteins. AB - The scope of this paper is to review approaches used for forced degradation (synonym, stress testing) of therapeutic proteins. Forced degradation studies play a central role in the development of therapeutic proteins, for example, for candidate selection, molecule characterization, formulation development, assay development, and comparability studies. Typical stress methods are addressed within this review, such as exposure to elevated temperatures, freeze-thawing, mechanical stress, oxidation, light, as well as various materials and devices used in the clinics during final administration. Stability testing is briefly described as far as relevant to the discussion of forced degradation studies. Whereas stability-testing requirements are defined in regulatory guidelines, standard procedures for forced degradation of therapeutic proteins are largely unavailable, except for photostability. Possible selection criteria to identify appropriate stress conditions and recommendations for setting up forced degradation studies for the different phases of development of therapeutic proteins are presented. PMID- 22083794 TI - Modification of poly(ether urethane) with fluorinated phosphorylcholine polyurethane for improvement of the blood compatibility. AB - In order to improve the blood compatibility, poly(ether urethane) (PEU) and fluorinated phosphorylcholine polyurethane (P-HFPC) were used to prepare PU/P HFPC blends by solution mixing. The hemocompatibility in vitro was evaluated with protein adsorption and platelet-rich plasma (PRP) contact tests. It was found that the amount of adsorbed protein on surface was decreased by 87%, and almost no platelet adhesion and activation was observed on the surface of blends when P HFPC content was above 5 wt %. After adding P-HFPC, the blends basically kept favorable mechanical properties of PEU though the content of P-HFPC rises to 20 wt %. To better understand the relationship between structure and properties, the phase structure and surface property of the blend films were further investigated via differential scanning calorimetry, dynamic mechanical analysis, atomic force microscopy, X-ray photoelectron spectroscopy, and contact angle measurements. The results indicated that the fluorinated phosphorylcholine units could be easily enriched on the surface of blend films due to the phase separation between the PEU and P-HFPC. Therefore, ordinary poly(ether urethane)s can obtain both satisfactory blood compatibility and good mechanical properties just by blending with small amount of P-HFPC. PMID- 22083793 TI - Shadow enhancers: frequently asked questions about distributed cis-regulatory information and enhancer redundancy. AB - This paper, in the form of a frequently asked questions page (FAQ), addresses outstanding questions about "shadow enhancers", quasi-redundant cis-regulatory elements, and their proposed roles in transcriptional control. Questions include: What exactly are shadow enhancers? How many genes have shadow/redundant/distributed enhancers? How redundant are these elements? What is the function of distributed enhancers? How modular are enhancers? Is it useful to study a single enhancer in isolation? In addition, a revised definition of "shadow enhancers" is proposed, and possible mechanisms of shadow enhancer function and evolution are discussed. PMID- 22083795 TI - Development of a biodegradable, temperature-sensitive dextran-based polymer as a cell-detaching substrate. AB - A biodegradable, temperature-sensitive dextran-allyl isocyanate-ethylamine (TSDAIE) as a nonenzymatic cell detachment polymeric substrate for human endothelial progenitor cells (EPCs) is developed and examined. The lower critical solution temperature of TSDAIE is determined; its phase transition occurrs at 18 to 22 degrees C. For EPC culture, cell culture flasks are coated with TSDAIE and type I collagen. The TSDAIE coating enables EPC detachment when the culture is cooled to 4 degrees C. The concentration of TSDAIE affects EPC attachment, which is thereby used to optimize the concentration of TSDAIE for coating. At the determined optimal concentration, TSDAIE is found to be compatible for use in EPC culture as revealed by cell attachment, spreading, proliferation, and phenotype. Overall, biodegradable TSDAIE shows promise for applications that culture and expand EPCs including vascular regenerative medicine and tissue engineering. PMID- 22083796 TI - Symptoms and signs of posterior circulation ischemia in the new England medical center posterior circulation registry. AB - OBJECTIVE: To evaluate the frequencies of symptoms and signs in patients with posterior circulation ischemia in a large case series of prospectively collected patients. DESIGN: Case series. SETTING: Outpatient and inpatient setting at the New England Medical Center, a tertiary care referral center in Boston, Massachusetts. PATIENTS: Consecutive sample of 407 adult patients who had stroke and/or transient ischemic attacks in the posterior circulation within 6 months of study inclusion. All patients were examined by senior stroke neurologists. All patients had either computed tomography or magnetic resonance imaging of the brain as well as vascular imaging of the head and neck. The study included 256 men (63%) and 151 women (37%). MAIN OUTCOME MEASURES: Frequencies of posterior circulation ischemic symptoms and signs. These outcome measures were planned before data collection began. Correlations between symptoms and signs with separate vascular territories of the posterior circulation were then analyzed. RESULTS: The most frequent posterior circulation symptoms were dizziness (47%), unilateral limb weakness (41%), dysarthria (31%), headache (28%), and nausea or vomiting (27%). The most frequent signs were unilateral limb weakness (38%), gait ataxia (31%), unilateral limb ataxia (30%), dysarthria (28%), and nystagmus (24%). Logistic regression analysis reveals that the clinical features dysphagia (P = .004; 95% CI, 1.8-24.4), nausea or vomiting (P = .002; 95% CI, 1.6-8.2), dizziness (P = .047; 95% CI, 1.0-5.4), and Horner syndrome (P = .001; 95% CI, 2.4 26.6) were positively correlated with the proximal vascular territory. Unilateral limb weakness (P = .001; 95% CI, 1.7-8.7) and cranial nerve VII deficits (P = .02; 95% CI, 1.1-5.3) were positively correlated with the middle territory. Limb sensory deficit (P = .001; 95% CI, 1.8-7.8), lethargy (P = .001; 95% CI, 2.3 12.4), and visual field loss (P = .001; 95% CI, 5.3-23.9) were positively correlated with the distal territory. CONCLUSIONS: We report the most frequent symptoms and signs in the largest published registry, the New England Medical Center Posterior Circulation Registry, of patients with posterior circulation ischemia who had complete neurological examinations and extensive cerebrovascular imaging. Knowledge of the vascular territory involved aids in the diagnosis of the causative vascular lesion and stroke mechanism. PMID- 22083797 TI - Clinical significance of rare copy number variations in epilepsy: a case-control survey using microarray-based comparative genomic hybridization. AB - OBJECTIVE: To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. DESIGN: Prospective cohort study. SETTING: Epilepsy centers in Italy. PATIENTS: Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. MAIN OUTCOME MEASURES: Identification of copy number variations (CNVs) and gene enrichment. RESULTS: Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = .03) and showed higher gene content (P = .02) than those in control subjects. The CNVs larger than 1 megabase (P = .002) and including more than 10 genes (P = .005) occurred more frequently in patients than in control subjects. Nine patients (34.6%) among those harboring rare CNVs showed rearrangements associated with emerging microdeletion or microduplication syndromes. Mental retardation and neuropsychiatric features were associated with rare CNVs (P = .004), whereas epilepsy type was not. The CNV rate in patients with epilepsy and mental retardation or neuropsychiatric features is not different from that observed in patients with mental retardation only. Moreover, significant enrichment of genes involved in ion transport was observed within CNVs identified in patients with epilepsy. CONCLUSIONS: Patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs, particularly when associated with mental retardation and neuropsychiatric features. The limited overlap between CNVs observed in the epilepsy group and those observed in the group with mental retardation only as well as the involvement of specific (ion channel) genes indicate a specific association between the identified CNVs and epilepsy. Screening for CNVs should be performed for diagnostic purposes preferentially in patients with epilepsy and mental retardation or neuropsychiatric features. PMID- 22083798 TI - The evaluation of distal symmetric polyneuropathy: a physician survey of clinical practice. AB - OBJECTIVE: To define current clinical practice for evaluating distal symmetric polyneuropathy. DESIGN: Using a modified Dillman method, we sent surveys to 600 internists, 600 neurologists, and 45 neuromuscular specialists selected from the American Medical Association Physician Masterfile. Survey questions pertained to which tests providers would order in the following 3 scenarios: (1) the initial evaluation of distal symmetric polyneuropathy, (2) the use of additional tests if the initial evaluation was unrevealing, and (3) patients with diabetes. The t test was used to compare the number of tests ordered by physician type, and the chi(2) test was used to compare proportions of tests ordered. SETTING: National survey of physicians. PARTICIPANTS: Internists, neurologists, and neuromuscular specialists. RESULTS: The response rate was 35%. Overall, many tests were ordered for the full evaluation of distal symmetric polyneuropathy (mean [SD], 16.5 [7.2] tests), and there was substantial variation within and between provider types. Internists ordered fewer tests (mean [SD], 14.5 [6.1] tests) than did neurologists (mean [SD], 17.5 [7.9] tests) (P < .001). Regarding the glucose tolerance test, substantial differences were found between physician types, with neurologists and neuromuscular specialists ordering this test more frequently (28.6% and 72.3%, respectively) and internists ordering it less frequently (4.1%). A brain and/or spine magnetic resonance imaging scan was ordered by 19.8% of internists and 12.9% of neurologists. CONCLUSIONS: From the supporting evidence, current practice intent on evaluating distal symmetric polyneuropathy is highly variable and differs widely. For this disorder of the peripheral nerves, a high-yield test such as the glucose tolerance test is rarely used, whereas magnetic resonance imaging is likely overused. Research that defines the optimal evaluation of distal symmetric polyneuropathy has the potential to result in more efficient care. PMID- 22083799 TI - Low serum vitamin D levels and recurrent inflammatory spinal cord disease. AB - BACKGROUND: Low 25-hydroxyvitamin D levels have been associated with a higher risk of developing multiple sclerosis and increased relapse rates in patients with multiple sclerosis. As a sterol hormone involved in multiple immunologic pathways, vitamin D may play a role in preventing monophasic immune-mediated central nervous system attacks from developing into recurrent disease. OBJECTIVE: To investigate the association between low serum vitamin D levels and recurrent spinal cord disease. DESIGN, SETTING, AND PATIENTS: We performed a retrospective analysis at Johns Hopkins Transverse Myelitis Center, Baltimore, Maryland, evaluating 25-hydroxyvitamin D levels in 77 patients with monophasic and recurrent inflammatory diseases of the spinal cord. MAIN OUTCOME MEASURE: Levels of 25-hydroxyvitamin D. RESULTS: Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race. CONCLUSIONS: This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease. PMID- 22083800 TI - The evolution of academic neurology: new information will bring new meaning. AB - We are on the cusp of what promises to be an era of unprecedented progress in neurology. Even with current fiscal constraints and serious concerns about how health care will be organized and financed, in the next 2 decades progress in neurology and neurological science will create important new insights into understanding the brain as we decipher its disorders and discover and apply effective treatments. PMID- 22083801 TI - Classification of cause of motor weakness in traumatic brain injury using diffusion tensor imaging. AB - BACKGROUND: Many studies have attempted to elucidate the causes of motor weakness in patients with traumatic brain injury (TBI). Most of these studies have focused on the specific cause of motor weakness. However, little is known about the classification and elucidation of the causes of motor weakness in consecutive patients with TBI. OBJECTIVE: To attempt to classify with diffusion tensor imaging the causes of motor weakness in patients with TBI by conducting an analysis of the injury mechanism of the corticospinal tract (CST). DESIGN: Retrospective study. SETTING: Rehabilitation department of a university hospital. Patients We recruited 41 consecutive patients who showed motor weakness among patients with TBI admitted for rehabilitation. MAIN OUTCOME MEASURES: We classified the causes of weakness according to the injury mechanism of the CST on diffusion tensor imaging. RESULTS: Injury mechanisms of the CST were classified as follows, in order: diffuse axonal injury, 24 patients (58.5%); traumatic intracerebral hemorrhage, 9 patients (21.9%); transtentorial herniation, 6 patients (14.6%); and focal cortical contusion, 4 patients (9.8%). In patients with diffuse axonal injury, the mean number of lesions composing CST injury was 3.6 (range, 2-6) and CST injury locations were as follows: the pons (61%), the cerebral peduncle (50%), the medulla (40%), the posterior limb of the internal capsule (17%), and the corona radiata (13%). CONCLUSION: We found that diffusion tensor imaging was useful in elucidation and classification of the causes of motor weakness resulting from CST injury in patients with TBI. PMID- 22083802 TI - Metastases to the oral region from pleural mesothelioma: Clinicopathologic review. AB - BACKGROUND: Malignant mesothelioma is a rare neoplasm that usually develops after exposure to asbestos and particularly involves the pleural cavity. It has a poor prognosis with aggressive local invasion and metastatic spread. METHODS: The literature relating to malignant mesothelioma metastatic to the oral region was reviewed. RESULTS: In all, 14 cases of malignant mesothelioma metastatic to the oral cavity were found. All were from pleural mesotheliomas, the tongue was the most common site of metastasis (8/14), and most metastases (9/13) were of the epithelioid type. The newly reported case is only the second report of a mesothelioma metastasizing to the buccal mucosa. It showed strong immunopositivity for keratin markers, vimentin, calretinin, and Wilms tumor product-1. CONCLUSIONS: The incidence of mesothelioma is predicted to continue to increase for at least another decade. Clinicians and pathologists should be aware of this lesion and its propensity to metastasize to the oral cavity. PMID- 22083803 TI - Catechol-O-methyltransferase Val158Met and the risk of dyskinesias in Parkinson's disease. AB - BACKGROUND: The A-allele of the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with decreased enzymatic activity and higher dopamine availability. METHODS: We studied 219 patients with PD who were free of dyskinesias at baseline and underwent thorough annual examinations. RESULTS: The A-allele of the COMT Val158Met polymorphism was related to an increased risk of developing dyskinesias during follow-up, in a dose-dependent manner (adjusted hazard ratios for the AG and AA genotypes [compared to GG]: 2.09 [95% confidence interval (CI), 1.07-4.06] and 2.81 [CI, 1.43-5.54], respectively). CONCLUSIONS: This finding suggests that genetic factors may affect susceptibility to dyskinesias in PD. PMID- 22083804 TI - Comparative activity and mechanism of action of three types of bovine antimicrobial peptides against pathogenic Prototheca spp. AB - The yeast-like algae of the genus Prototheca are ubiquitous saprophytes causing infections in immunocompromised patients and granulomatous mastitis in cattle. Few available therapies and the rapid spread of resistant strains worldwide support the need for novel drugs against protothecosis. Host defence antimicrobial peptides inactivate a wide array of pathogens and are a rich source of leads, with the advantage of being largely unaffected by microbial resistance mechanisms. Three structurally diverse bovine peptides [BMAP-28, Bac5 and lingual antimicrobial peptide (LAP)] have thus been tested for their capacity to inactivate Prototheca spp. In minimum inhibitory concentration (MIC) assays, they were all effective in the micromolar range against clinical mastitis isolates as well as a Prototheca wickerhamii reference strain. BMAP-28 sterilized Prototheca cultures within 30-60 min at its MIC, induced cell permeabilization with near 100% release of cellular adenosine triphosphate and resulted in extensive surface blebbing and release of intracellular material as observed by scanning electron microscopy. Bac5 and LAP inactivated Prototheca following 3-6 h incubation at fourfold their MIC and did not result in detectable surface damage despite 70-90% killing, suggesting they act via non-lytic mechanisms. In circular dichroism studies, the conformation of BMAP-28, but not that of Bac5 or LAP, was affected by interaction with liposomes mimicking algal membranes. Our results indicate that BMAP-28, Bac5 and LAP kill Prototheca with distinct potencies, killing kinetics, and modes of action and may be appropriate for protothecal mastitis treatment. In addition, the ability of Bac5 and LAP to act via non-lytic mechanisms may be exploited for the development of target-selective drugs. PMID- 22083810 TI - MG132 treatment during oocyte maturation improves embryonic development after somatic cell nuclear transfer and alters oocyte and embryo transcript abundance in pigs. AB - The objective of this study was to examine the effect of treating pig oocytes during in vitro maturation (IVM) with a proteasome inhibitor, MG132, on oocyte maturation and embryonic development. In one series of experiments, oocytes from medium-sized follicles (3-8 mm in diameter) were untreated (MCO) or treated with MG132 during 0-22 hr (M0-22) or 30-42 hr (M30-42) of IVM. There was no significant effect of MG132 on nuclear maturation or cytoplasmic maturation (as assessed by intracellular amounts of glutathione and p34cdc2 kinase activity). Blastocyst formation after parthenogenetic activation (PA) and somatic cell nuclear transfer (SCNT), however, was increased for M30-42 (65.2% and 27.7% for PA and SCNT, respectively) compared to MCO (42.6% and 13.6%, respectively) and M0 22 (45.3% and 19.5%, respectively; P<0.05). Expression of PCNA and ERK2 was increased in M30-42 for IVM oocytes while transcript abundance for POUF51, DNMT1, FGFR2, and PCNA was increased in M30-42 for 4-cell SCNT embryos. When oocytes derived from small follicles (<3 mm in diameter) were untreated (SCO) or treated with MG132 during 0-22 hr (S0-22), 30-42 hr (S30-42) of IVM, or 0-22 and 30-42 hr of IVM (S0-22/30-42), expression of POU5F1, DNMT1, FGFR2, and PCNA and blastocyst formation were increased for SCNT embryos derived from S30 to 42 (16.5%) and S0 22/30-42 oocytes (20.8%) as compared to embryos from SCO (8.7%) or S0-22 oocytes (8.8%; P<0.05). Results demonstrate that treatment of oocytes with MG132 during the later stage of IVM improves embryonic development and alters gene expression in pigs. PMID- 22083811 TI - Concentration-dependent displacement of cholesterol in micelles by hydrophobic rice bran protein hydrolysates. AB - BACKGROUND: Rice bran, containing about 100-150 g kg(-1) protein, is a by-product of rice milling that has only become an available ingredient in recent years owing to the centralisation of rice milling. Rice bran, but not its protein fraction or hydrolysates, has been shown to have a hypocholesterolaemic effect. Peptides from soy, milk and other foods have been proposed to have hypocholesterolaemic effects based on their ability to lower cholesterol solubility in bile acid/phosphotidyl choline micelles. RESULTS: Rice bran protein hydrolysates (RBPHs) were prepared and investigated for their potential to lower cholesterol concentration in micelles. The RBPHs were produced by digestion using four different peptidases, alcalase 2.4L((r)), neutrase 0.8L((r)), papaya latex papain and porcine pancreas trypsin, and then fractionated by hydrophobicity using styrene/divinylbeneze resins. Alcalase 2.4L((r)) produced the highest degree of hydrolysis, and the resulting hydrolysates had the highest micellar cholesterol inhibition ability in an in vitro hypocholesterolaemic test. The adsorption dynamics of four different macroporous resins, DA201-C, Sepabeads SP207 and SP825 and Diaion HP20, were determined using the Langmuir isotherm model. DA201-C had the highest adsorption capacity with an equilibrium concentration of 220 mg g(-1). The hydrolysates eluted with 25, 50, 75 and 95% (v/v) ethanol lowered the micellar cholesterol concentration by 11.88, 14.76, 19.37 and 7.56% respectively. CONCLUSION: A hydrophobic fraction of RBPH had the highest inhibitory activity on micellar cholesterol, which suggests that it may have hypocholesterolaemic properties. PMID- 22083812 TI - Optimized conditions for a quantitative SELDI TOF MS protein assay. AB - The development of peptide/protein analyte assays for the purpose of diagnostic tests is driven by multiple factors, including sample availability, required throughput, and quantitative reproducibility. Laser Desorption/ionization mass spectrometry methods (LDI-MS) are particularly well suited for both peptide and protein characterization, and combining chromatographic surfaces directly onto the MS probe in the form of surface enhanced laser desorption/ionization (SELDI) biochips has improved the reproducibility of analyte detection and provided effective relative quantitation. Here, we provide methods for developing reproducible SELDI-based assays by providing a complex artificial protein matrix background within the sample to be analyzed that allows for a common and reproducible ionization background as well as internal normalization standards. Using this approach, quantitative assays can be developed with CVs typically less than 10% across assays and days. Although the method has been extensively and successfully implemented in association with a protein matrix from E. coli, any other source for the complex protein matrix can be considered as long as it adheres to a set of conditions including the following: (1) the protein matrix must not provide interferences with the analyte to be detected, (2) the protein matrix must be sufficiently complex such that a majority of ion current generated from the desorption of the sample comes from the complex protein matrix, and (3) specific and well-resolved protein matrix peaks must be present within the mass range of the analyte of interest for appropriate normalization. PMID- 22083813 TI - Solid-phase fractionation strategies applied to proteomics investigations. AB - Methods for protein fractionation in the proteomics investigation field are relatively numerous. They apply to the prefractionation of the sample to obtain less complex protein mixtures for an easier analysis; they are also used as a means to evidence specific proteins or protein classes otherwise impossible to detect. They involve depletion of high-abundance proteins suppressing the signal of dilute species; they are also capable to enhance the detectability of low abundance species while concomitantly decreasing the concentration of abundant proteins such as albumin in serum and hemoglobin in red blood cell lysates. Fractionation of proteomes is also used for the isolation of targeted species that are selected for their different expression under certain pathological conditions and that are detected by mass spectrometry. Two unconventional methods of large interest in proteomics due to the low level of protein redundancy between fractions are also reported.All these methods are reviewed and detailed method given to allow specialists of proteomics investigation to access selected separation methods generally dispersed on different technical reviews or books. PMID- 22083814 TI - Data processing and analysis using ProteinChip(r) data manager software. AB - Mass spectrometry-based clinical proteomics and biomarker research require the processing of large numbers of patient samples in order to attain the statistical significance required to produce robust biomarker candidates. When processed using the high-sensitivity and high-throughput Surface Enhanced Laser Desorption/Ionization ProteinChip SELDI system, the result is an enormous amount of mass spectrometric profiling data. The time and effort required to mine this data and the quality of the candidate biomarkers generated is largely dependent on the quality and appropriate use of the software tools available. This chapter describes the typical workflow for processing and analyzing SELDI data using both univariate and unsupervised multivariate analysis tools. PMID- 22083815 TI - Purification and identification of candidate biomarkers discovered using SELDI TOF MS. AB - Purification and identification of candidate biomarkers is a critical step in the biomarker development process, since it provides insight into the disease biology and facilitates the development of analyte-specific assays. Top-down biomarker discovery workflows like SELDI-TOF MS yield candidate markers that are identified based on native mass. Positive identification of these candidate biomarkers requires further enrichment and/or purification. While purification methods must be optimized for each protein target, there are two general workflows. Native peptides under approximately 4 kDa can be subjected to direct sequence analysis using a tandem mass spectrometer whereas proteins over approximately 4 kDa usually require proteolytic digestion prior to MS/MS analysis. In both cases, partial purification is usually necessary to enrich the candidate biomarker relative to other proteins in a complex biological mixture. This chapter provides detailed protocols for protein purification (including anion exchange, metal affinity, and reverse phase chromatography as well as SDS-PAGE) and identification (including protein processing, digestion, and database searching). PMID- 22083816 TI - Biomarker discovery in serum/plasma using surface enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry. AB - Proteins and peptides that undergo variations in concentration or state as a result of a biological process or disease may be used as biomarkers for the diagnosis or prognosis of diseases and/or for the monitoring of therapy. Serum/plasma is one of the most easily obtained patient specimens and contains thousands of proteins produced and secreted from cells and tissues. While serum/plasma is a valuable specimen for protein biomarker research, especially in the area of infectious diseases, the dynamic range of the proteome presents a technical challenge. Serum/plasma is dominated by high abundance proteins, such as albumin, immunoglobulins, haptogloblulin, which constitute almost 90% of the total serum/plasma protein by weight and make the detection of the low abundance proteins difficult. Therefore, effective fractionation and separation methods are essential to detect potential biomarker proteins present in small quantities for mass spectrometry.The current tests for blood-borne protozoan diseases are inadequate by monitoring treatment efficacy or for prognosis and also lack sensitivity and specificity. To overcome these limitations, we began a program to develop novel assays for infectious diseases using mass spectrometric data directly as well as "next generation" assays that exploit the richness of the MS data converted to standard platforms. Here we focus on high-throughput fractionation and proteomic analysis using Surface Enhanced Laser Desorption Ionization Time of Flight (SELDI-TOF) mass spectrometry platform. Separation and enrichment is achieved using stepwise anion exchange fractionation prior to analysis on multiple ProteinChip array chemistries. We have used this approach successfully to identify proteins/peptides or protein "profiles" (biomarkers) in subjects chronically infected with blood-borne protozoan parasites (i.e. Chagas disease, babesia, toxoplasma, malaria), fascioliosis, and cysticercosis. PMID- 22083818 TI - Profiling of urine using ProteinChip(r) technology. AB - Urine is an extremely valuable sample type for biomarker discovery due to the non invasive collection and the relatively low protein content, which makes detection of perturbations associated with disease easier. SELDI-TOF analysis is ideally suited for analysis of urine since the chromatographic capture mechanism can tolerate salt and urea in the urine sample that would otherwise need to be removed prior to mass spectrometric analysis. While neat urine can be analyzed directly on ProteinChip arrays, urine can also benefit from an enrichment step, which has been shown to increase the number of proteins detected more than twofold. Because urine volume and contents can vary substantially between individuals and within individuals over time, sample collection and storage should be carefully controlled to assure reproducible and clinically relevant results. PMID- 22083817 TI - Plasma proteomic profiling of pediatric osteosarcoma. AB - The development of a sensitive, specific, and non-invasive approach for cancer detection will facilitate early detection and, hence, improve the outcome of individuals with known cancer predispositions. Proteomic profiling of blood emerges to be a logical choice of such non-invasive or minimal invasive detection. However, plasma biomarker discovery of pediatric cancers lags behind that of adult cancers, suggesting more efforts are needed in this area. In this study, we used surface-enhanced laser desorption/ionization-time of flight mass spectrometry to profile plasma proteome in osteosarcoma patients. Osteosarcoma is a bone cancer that affects many children and young adults. We have shown that the plasma proteome contains a unique cancer signature that can distinguish patients with osteosarcoma from those with a benign bone disease. To improve cancer biomarker discovery in plasma, we have also shown that depletion of two highly abundant plasma proteins increases the detection sensitivity of lower-abundance proteins. The combination of depletion and proteomic profiling may increase the chance of identifying tumor-derived proteins within the plasma of pediatric cancer patients. PMID- 22083819 TI - Protein profiling of cerebrospinal fluid. AB - The cerebrospinal fluid (CSF) perfuses the brain and spinal cord. CSF contains proteins and peptides important for brain physiology and potentially also relevant for brain pathology. Hence, CSF is the perfect source to search for new biomarkers to improve diagnosis of neurological diseases as well as to monitor the performance of disease-modifying drugs. This chapter presents methods for SELDI-TOF profiling of CSF as well as useful advice regarding pre-analytical factors to be considered. PMID- 22083820 TI - SELDI-TOF mass spectrometry-based protein profiling of tissue samples for toxicological studies. AB - Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) has become a popular method for protein profiling in clinical diagnosis, as well as in toxicological studies. It combines solid-phase chromatography with TOF-MS on a single platform, which enables the application of crude samples, such as plasma or tissue lysate. In this chapter, we outline two methods that enable the extraction of proteins from tissue samples for subsequent application on ProteinChip arrays. The first method is the extraction of proteins only from tissue using simply lysis buffers. The second method is helpful if proteins, as well as RNA or DNA, should be extracted from one and the same piece of tissue and is based on phenol-chloroform separation. Although initially developed for liver and kidney tissue both methods can be used for other tissue types. PMID- 22083821 TI - Proteomic analysis of skeletal muscle tissue using SELDI-TOF MS: application to disuse atrophy. AB - Skeletal muscle atrophy in response to disuse/unloading is a complex adaptation that involves many components of the muscle tissue. The underlying mechanisms that initiate and control the loss of muscle tissue during this response, especially contractile proteins located within the myofibers, are as yet unclear. One approach capable of distinguishing protein changes specifically associated with disuse/unloading-induced skeletal muscle atrophy is to compare the proteomic profiles of similar muscles between control, unloaded/atrophied, and unloaded/"atrophy-protected" experimental conditions. By utilizing a subtractive proteomic analysis approach, those proteins specifically modulated during the atrophic response can be identified and discriminated from those associated with disuse in general. We here describe the use of SELDI-TOF MS coupled with micro scale preparative ion-exchange chromatography to detect proteins potentially specifically associated with the atrophic response in rat skeletal muscle. PMID- 22083822 TI - Profiling cervical lavage fluid by SELDI-TOF mass spectrometry. AB - The mucosal surface of the female genital tract is the first site of contact for many sexually transmitted infections and serves as the first layer of defense. This layer has components of both the innate and adaptive immune systems to protect against infections. For these reasons, this fluid is a major focus of study to understand the pathogenesis of different infectious diseases. Novel tools are available to allow for the analysis of the components of this mucosal layer, including the area of proteomics. The emergence of proteomics has allowed for the development of many types of platforms for protein profiling, including gel-based technologies (2-dimensional differential in-gel electrophoresis) and mass spectrometry-based techniques. SELDI-TOF, a mass spectrometry-based platform coupled to on-chip chromatographic separation, has been developed as a high throughput technique to profile complex protein samples. This chapter will outline detailed methods to profile cervical mucosal samples by SELDI-TOF and can serve as a guideline for other types of mucosal samples. PMID- 22083823 TI - Isolation and proteomic analysis of platelets by SELDI-TOF MS. AB - Many growth factors, leukotrines, and biological ligands are not circulating free in plasma or serum, except in the case of late or disseminated disease. During early tumor growth and angiogenesis, platelets actively and selectively sequester regulators of angiogenesis and, as such, the platelet protein content can be used as a marker of early tumor growth or angiogenesis. With the recent increase in the clinical use of biologic modifiers in cancer and chronic disease therapy, the search for markers of early disease, therapeutic response, and/or recurrence has suggested that analysis of platelet proteins may be more relevant and accurate. We provide a guideline for the proteomic analysis of platelet proteome, placing specific emphasis on angiogenesis regulators, even though other platelet proteins may serve as markers of disease in the future. The analysis of serum/plasma has been fraught with difficulties because of the extraordinarily large number of proteins and because some of the proteins are contained in extraordinarily large amounts, masking the less abundant proteins. Thus, platelets may provide a much more biologically relevant analyte for biomarker discovery. PMID- 22083824 TI - Using SELDI-TOF mass spectrometry on amniotic fluid and for clinical proteomics and theranostics in disorders of pregnancy. AB - Clinical proteomics encompasses a multitude of experimental approaches, tools, and techniques based on proteomics technology which are directly aimed to accelerate and improve diagnosis and treatment of human diseases. Surface enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectrometry is a variant of matrix-enhanced laser desorption ionization (MALDI) that makes use of chemically-modified surfaces to reduce the complexity of biological samples prior to separation in the mass analyzer. Compared to other proteomic techniques, SELDI has several important advantages such as ability to analyze complex biological samples with minimal pre-processing, ease of handling and high throughput. Importantly, once the biomarker or combination of biomarkers with potential clinical value has been established, validation analyses can be conducted in close proximity to clinical settings which is important for establishing the utility of new diagnostics in clinical decision making and perhaps future theranostic interventions. This chapter provides protocols for experimental design and methodology aimed at (1) discovering biologically relevant biomarkers in amniotic fluid using SELDI-TOF; (2) validating the clinical utility of the biomarkers as new diagnostics; (3) translating the biomarker findings into pathophysiological phenomena to provide further insight and extend the current understanding of the disease process. Many of the principles described herein for amniotic fluid could be generalized to studies involving other types of biological samples and other clinical questions. PMID- 22083826 TI - Analysis of protein-protein interaction using proteinchip array-based SELDI-TOF mass spectrometry. AB - Protein-protein interactions are key elements in the assembly of cellular regulatory and signaling protein complexes that integrate and transmit signals and information in controlling and regulating various cellular processes and functions. Many conventional methods of studying protein-protein interaction, such as the immuno-precipitation and immuno-blotting assay and the affinity column pull-down and chromatographic analysis, are very time-consuming and labor intensive and lack accuracy and sensitivity. We have developed a simple, rapid, and sensitive assay using a ProteinChip array and SELDI-TOF mass spectrometry to analyze protein-protein interactions and map the crucial elements that are directly involved in these interactions. First, a purified "bait" protein or a synthetic peptide of interest is immobilized onto the preactivated surface of a PS10 or PS20 ProteinChip and the unoccupied surfaces on the chip are protected by application of a layer ethanolamine to prevent them from binding to other non interactive proteins. Then, the target-containing cellular protein lysate or synthetic peptide containing the predicted amino acid sequence of protein interaction motif is applied to the protected array with immobilized bait protein/peptide. The nonspecific proteins/peptides are washed off under various stringent conditions and only the proteins specifically interacting with the bait protein/peptide remain on the chip. Last, the captured interacting protein/peptide complexes are then analyzed by SELDI-TOF mass spectrometry and their identities are confirmed by their predicted distinctive masses. This method can be used to unambiguously detect the specific protein-protein interaction of known proteins/peptides, to easily identify potential cellular targets of proteins of interest, and to accurately analyze and map the structural elements of a given protein and its target proteins using synthetic peptides with the predicted potential protein interaction motifs. PMID- 22083827 TI - Quantitation of amyloid beta peptides in CSF by surface enhanced MALDI-TOF. AB - Alzheimer's disease is characterized by the deposition of amyloid plaques in the brain. The major components of these plaques are beta-amyloid (Abeta) peptides. The CSF concentration of these peptides can therefore provide a valuable biomarker for potentially predicting the state of disease and/or monitoring the efficacy of a drug aiming to inhibit the formation of amyloid plaques. Although the concentration of a given peptide in CSF can easily be measured by ELISA methods, few methods are able to simultaneously observe and distinguish between various peptides of similar yet slightly different amino acid composition. The Surface Enhanced Laser Desorption/Ionization-Time Of Flight mass spectrometry (SELDI-TOF) technology, a platform combining the use of an antibody and MALDI TOF, can be used to simultaneously detect and quantitate various Abeta peptides with sensitivities in the picomolar range. PMID- 22083825 TI - High throughput profiling of serum phosphoproteins/peptides using the SELDI-TOF MS platform. AB - Protein phosphorylation is a dynamic post-translational modification that plays a critical role in the regulation of a wide spectrum of biological events and cellular functions including signal transduction, gene expression, cell proliferation, and apoptosis. Determination of the sites and magnitudes of protein phosphorylation has been an essential step in the analysis of the control of many biological systems. A high throughput analysis of phosphorylation of proteins would provide a simple, logical, and useful tool for a functional dissection and prediction of biological functions and signaling pathways in association with these important molecular events. We have developed a functional proteomics technique using the ProteinChip array-based SELDI-TOF-MS analysis for high throughput profiling of phosphoproteins/phosphopeptides in human serum for the early detection and diagnosis as well as for the molecular staging of human cancer. The methodology and experimental approach consists of five steps: (1) generation of a total peptide pool of serum proteins by a global trypsin digestion; (2) rapid isolation of phosphopeptides from the total serum peptide pool by an affinity selection, purification, and enrichment using a novel automated micro-bioprocessing system with phospho-antibody-conjugated paramagnetic beads and a hybrid magnet plate; (3) high throughput phosphopeptide analysis on ProteinChip arrays by automated SELDI-TOF-MS; and (4) bioinformatics and statistical methods for data analysis. This method with appropriate modifications may be equally applicable to serine-, threonine- and tyrosine phosphorylated proteins and for selectively isolating, profiling, and identifying phosphopeptides present in a highly complex phosphor-peptide mixture prepared from various human specimens such as cells, tissue samples, and serum and other body fluids. PMID- 22083828 TI - Impact of the extraction procedure on the kinetics of anthocyanin and colour degradation of roselle extracts during storage. AB - BACKGROUND: The stability of anthocyanins and colour of aqueous extracts from roselle (Hibiscus sabdariffa L.) was investigated during storage at 4-45 degrees C. The effect of the extraction procedure (cold or hot extraction with or without pasteurisation) on the kinetic behaviour was determined. RESULTS: Data analysis showed first-order kinetics for the evolution of anthocyanin content, colour density, colour strength and browning index. Three models (Arrhenius, Eyring and Ball) were used to represent the temperature dependence of the reaction rates. The three models allowed the prediction of colour modifications according to the storage temperature over 6 months. Activation energies ranged from 22 to 26 kJ mol(-1) for anthocyanin degradation and from 18 to 34 kJ mol(-1) for colour parameter modification. The degradation rate during storage depended on the extraction procedure. When heated, the extracts were clearly less stable. Their colour changed faster during storage especially when hot water and pasteurisation were used. CONCLUSION: Although the anthocyanin content and initial colour were not modified, the extraction conditions, especially temperature, greatly affected the stability of the extracts during storage. Further studies are needed to understand the mechanisms involved. PMID- 22083829 TI - Label-free identification and characterization of human pluripotent stem cell derived cardiomyocytes using second harmonic generation (SHG) microscopy. AB - Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) are a potentially unlimited source of cardiomyocytes (CMs) for cardiac transplantation therapies. The establishment of pure PSC-CM populations is important for this application, but is hampered by a lack of CM-specific surface markers suitable for their identification and sorting. Contemporary purification techniques are either non specific or require genetic modification. We report a second harmonic generation (SHG) signal detectable in PSC-CMs that is attributable to sarcomeric myosin, dependent on PSC-CM maturity, and retained while PSC-CMs are in suspension. Our study demonstrates the feasibility of developing a SHG-activated flow cytometer for the non-invasive purification of PSC-CMs. PMID- 22083830 TI - Effects of PEGylation and immune complex formation on the pharmacokinetics and biodistribution of recombinant interleukin 10 in mice. AB - Interleukin 10 (IL-10) is a potent cytokine homodimer with multiple immunoregulatory functions. Here, we have characterized the effects of PEGylation and formation of human IL-10 (hIL-10)/humanized anti-human IL-10 (halphahIL-10) immune complexes in the pharmacokinetics, biodistribution, and biotransformation of IL-10 in mice. To assess the fate of native, PEGylated, and antibody-bound IL 10; we implemented an analytical set of fluorescence emission-linked assays. Plasma size exclusion chromatography analysis indicated that fluoro-labeled native and PEGylated murine IL-10 (PEG-mIL-10) are stable in the circulation. PEGylation of IL-10 resulted in a 21-fold increased exposure, 2.7-fold increase in half-life, and 20-fold reduction in clearance. Kidney is the major organ of disposition for both native and PEGylated mIL-10 with renal uptake directly related to systemic clearance. The fluorescence signal in the kidneys reached tissue/blood ratios up to 150 and 20 for native and PEG-mIL-10, respectively. hIL 10/halphahIL-10 immune complexes are detectable in the circulation without evidence of unbound or degraded hIL-10. The exposure of hIL-10 present in immune complexes versus that of hIL-10 alone increased from 0.53 to 11.28 MUg . day/ml, with a half-life of 1.16 days and a 23-fold reduction in clearance. Unlike hIL-10 alone, antibody-bound hIL-10 was targeted mainly to the liver with minimal renal distribution. In addition, we found an 11-fold reduction (from 9.9 to 113 nM) in binding to the neonatal Fc receptor (FcRn) when the halphahIL10 antibody is conjugated to hIL-10. The potential changes in FcRn binding in vivo and increased liver uptake may explain the unique pharmacokinetic properties of hIL 10/halphahIL-10 immune complexes. PMID- 22083831 TI - Quantitative analysis of free flap volume changes in head and neck reconstruction. AB - BACKGROUND: The purpose of this study was to determine whether free flap volume decreases or increases in the long-term postoperative period. METHODS: We used a retrospective analysis of 17 patients to measure muscle and fat volume in free flap with 3-dimensional (3D) images using the AZE Virtual Place Lexus64. RESULTS: Seventeen patients underwent free flap reconstruction with rectus abdominis musculocutaneous flaps (n = 11) or anterolateral thigh flaps (n = 6). Median follow-up was 28.9 months (range, 2.1-48.4 months). Total flap volume was significantly decreased in flaps including >=40% muscle (p = .011). Mean final muscle volume was 50% at an average of 12 months. Final fat volume was significantly higher for cases with no evidence of disease (mean, 116.7%) than for died-of-the-disease cases (mean, 70.3%; p = .007). CONCLUSION: Use of free flaps with a high ratio of fat to muscle is sustainable and can gain volume over time, as transplanted fat can increase depending on host condition. PMID- 22083832 TI - Antibiotic prophylaxis in cardiac surgery: systematic review and meta-analysis. AB - BACKGROUND: Antibiotic prophylaxis is recommended in cardiac surgery. Current debate concerns the type of antibiotic(s), dosing and the duration of prophylaxis. METHODS: Systematic review of randomized controlled trials comparing one antibiotic regimen versus another in cardiac surgery. We searched The Cochrane Library, PubMed, LILACS, conference proceedings and bibliographies. Two reviewers independently extracted the data. The primary outcome was deep sternal wound infections (DSWIs). Meta-analysis was performed using the Mantel-Haenszel fixed-effect method. Risk ratios (RRs) with 95% confidence intervals (95% CIs) are reported. RESULTS: Fifty-nine trials were included. There were no significant differences in DSWI or all other categories of surgical site infections (SSIs) for antibiotic prophylaxis with beta-lactams comprising a Gram-negative spectrum of coverage versus prophylaxis targeting Gram-positive bacteria, but the former led to a significantly lower rate of post-operative pneumonia (RR 0.68, 95% CI 0.51-0.90) and all-cause mortality (RR 0.66, 95% CI 0.47-0.92). In trials comparing different antibiotic regimens for different durations, prophylaxis duration of <=24 h post-operation led to higher rates of DSWI (RR 1.83, 95% CI 1.25-2.66), any sternal SSI, surgical interventions for SSI and endocarditis compared with longer duration prophylaxis. There was no advantage of regimens lasting >48 h post-operation. In the comparison of glycopeptides versus beta lactams, an advantage of glycopeptides was observed when comparators were given for similar duration and for beta-lactams when given for a longer duration than the glycopeptides. There was no significant advantage of high antibiotic dosing. CONCLUSIONS: Evidence supports second- or third-generation cephalosporins for cardiac surgery prophylaxis and points at a possible advantage of prophylaxis prolongation up to 48 h post-operatively. PMID- 22083833 TI - Streptavidin-coated TiO2 surfaces are biologically inert: protein adsorption and osteoblast adhesion studies. AB - Non-fouling TiO2 surfaces are attractive for a wide range of applications such as biosensors and medical devices, where biologically inert surfaces are needed. Typically, this is achieved by controlled surface modifications which prevent protein adsorption. For example, polyethylene glycol (PEG) or PEG-derived polymers have been widely applied to render TiO2 surfaces biologically inert. These surfaces have been further modified in order to achieve specific bio activation. Therefore, there have been efforts to specifically functionalize TiO2 surfaces with polymers with embedded biotin motives, which can be used to couple streptavidin for further functionalization. As an alternative, here a streptavidin layer was immobilized by self-assembly directly on a biotinylated TiO2 surface, thus forming an anti-adhesive matrix, which can be selectively bio activated. The anti-adhesive properties of these substrates were analyzed by studying the interaction of the surface coating with fibronectin, lysozym, and osteoblast cells using surface plasmon resonance spectroscopy, atomic force microscopy, and light microscopy. In contrast to non-modified TiO2 surfaces, streptavidin-coated TiO2 surfaces led to a very biologically inert substrate, making this type of surface coating a promising alternative to polymer coatings of TiO2 surfaces. PMID- 22083834 TI - Chemical control of spin propagation between heterometallic rings. AB - We present a synthetic, structural, theoretical, and spectroscopic study of a family of heterometallic ring dimers which have the formula [{Cr(7)NiF(3)(Etglu)(O(2)CtBu)(15)}(2)(NLN)], in which Etglu is the pentadeprotonated form of the sugar N-ethyl-D-glucamine, and NLN is an aromatic bridging diimine ligand. By varying NLN we are able to adjust the strength of the interaction between rings with the aim of understanding how to tune our system to achieve weak magnetic communication between the spins, a prerequisite for quantum entanglement. Micro-SQUID and EPR data reveal that the magnetic coupling between rings is partly related to the through-bond distance between the spin centers, but also depends on spin-polarization mechanisms and torsion angles between aromatic rings. Density functional theory (DFT) calculations allow us to make predictions of how such chemically variable parameters could be used to tune very precisely the interaction in such systems. For possible applications in quantum information processing and molecular spintronics, such precise control is essential. PMID- 22083835 TI - Solution structure by nuclear magnetic resonance of the two lantibiotics 97518 and NAI-107. AB - Lantibiotics 97518 and NAI-107, produced by the related genera Planomonospora and Microbispora respectively, are members of a family of nisin-related compounds. They represent promising compounds to treat infections caused by multiresistant Gram-positive pathogens. Despite their similar structure and a similar antibacterial spectrum, the two lantibiotics exhibit significant differences in their potency. To gain an insight into the structure-activity relationships, their conformational properties in solution are determined by NMR. After carrying out an NOE analysis of 2D (1)H NMR spectra, high-resolution 3D structures are determined using molecular dynamics simulations. PMID- 22083836 TI - Dentatorubral-pallidoluysian atrophy: haplotype of Asian origin in 2 Italian families. PMID- 22083837 TI - Expert's comment concerning Grand Rounds case entitled "Congenital kypho scoliosis: a case of thoracic insufficiency syndrome and the limitations of treatment" (by A.D. Chatterjee, K. Hassan and M.P. Grevitt). PMID- 22083838 TI - Iliac crest orientation and geometry in able-bodied and non-treated adolescent idiopathic scoliosis girls with moderate and severe spinal deformity. AB - PURPOSE: To identify pelvic rotation and/or distortion in able-bodied and untreated AIS girls with moderate and severe scoliosis and verify association of pelvic morphological changes with Cobb angle increase. METHODS: The 3D coordinates of nine anatomic bony landmarks were identified to estimate pelvic orientation using a Flock of Birds system. The distances between the first sacral vertebral body (S1) and each of the eight iliac spine landmarks in all three planes were calculated to identify pelvic distortion. Analysis of variance was used to assess pelvic orientation and determine pelvic distortion. Pearson coefficients of correlation were used to identify any relationships between Cobb angle and pelvic morphological parameters. RESULTS: Pelvic orientation was similar in able-bodied and scoliotic girls regardless of the severity of the spinal deformity. Significant differences were observed in pelvic morphology between AIS with severe untreated scoliosis and those with a moderate scoliosis for the right anterosuperior iliac spines (ASIS), the tip of the superior iliac crest (TSIC) and the widest tip of the iliac crest (WTIC) widths from S1. Statistically significant correlations were observed between the Cobb angles and the iliac crest distances measured from S1. CONCLUSIONS: Differences in iliac spine geometries occurred in the transverse plane correlating to Cobb angles which suggest altered bone growth in AIS girls. Such findings could indicate right thoracic spinal deformity as a result of pelvic torsion. PMID- 22083839 TI - The Nottingham Hip Fracture Score as a predictor of early discharge following fractured neck of femur. AB - BACKGROUND: hip fracture represents a huge medical, social and financial burden on patients, their carers and the health and social care systems. For survivors, return to their own home may be a key outcome. The Nottingham Hip Fracture Score (NHFS) is a validated score, based on admission characteristics, for predicting 30-day and 1-year mortality that may be of benefit in predicting return-to-home, directly from the acute orthopaedic ward. OBJECTIVE: to assess the utility of the NHFS as a predictor of return-to-home in patients following hip fracture. METHODS: the NHFS was calculated for all patients admitted from their own home and the correlation between the NHFS and eventual return-to-home was calculated, as well as the probability of discharge by within 7, 14 and 21 days. RESULTS: a total of 6,123 patients were available for analysis. Of which, 3,699 (60%) were discharged from acute hospital to their own home. Increasing NHFS was negatively correlated with eventual return-to-home (r(2) = 0.949) and with the proportion of patients discharged back to their own home at 7, 14 and 21 postoperative days, respectively (r(2) = 0.84, 0.94, 0.96, respectively). CONCLUSIONS: the NHFS is a reliable tool for predicting return-to-home. It may be useful for discharge planning, and for the design of future research trials. PMID- 22083840 TI - Is there a role for physical activity in preventing cognitive decline in people with mild cognitive impairment? AB - Mild cognitive impairment (MCI) is a common clinical syndrome that identifies people at high risk of developing dementia. Although treatments for MCI are currently unavailable, preliminary evidence has identified potential neuro protective effects of physical activity, which may lead to improved outcomes. However, there is uncertainty regarding the effectiveness, feasibility and acceptability of this treatment strategy. These uncertainties require further investigation before physical activity interventions can be recommended for routine care. PMID- 22083841 TI - Computational chemistry in pharmaceutical research: at the crossroads. AB - Computational approaches are an integral part of pharmaceutical research. However, there are many of unsolved key questions that limit the scientific progress in the still evolving computational field and its impact on drug discovery. Importantly, a number of these questions are not new but date back many years. Hence, it might be difficult to conclusively answer them in the foreseeable future. Moreover, the computational field as a whole is characterized by a high degree of heterogeneity and so is, unfortunately, the quality of its scientific output. In light of this situation, it is proposed that changes in scientific standards and culture should be seriously considered now in order to lay a foundation for future progress in computational research. PMID- 22083842 TI - Intragenomic conflict of maternal HLA haplotypes: a potential link between vigorous intrauterine growth and risk of autoimmunity in adulthood. PMID- 22083843 TI - [Package leaflets of pharmaceutical products - a closed book?]. PMID- 22083844 TI - Spatiotemporal control over growth factor delivery from collagen-based membrane. AB - Exogenous administration of growth factors has been identified as a potential therapeutic approach for healing wounds. A way to enhance the efficacy of growth factors would be to achieve spatiotemporal control over their delivery to desired sites for an extended period. In this study, we designed and prepared a kind of double-layered collagen membrane, a dense layer and a loose layer, which incorporated basic fibroblast growth factor (bFGF)-loaded chitosan-heparin nanoparticles. The nanoparticles were prepared by polyelectrolyte gelation process and then were sandwiched between the two layers of collagen membrane. The release of model protein human serum albumin (HSA) from the double-layered membrane was tracked by radio-label assay, and the bioactivity of the growth factor on fibroblast cell (L929) was evaluated by MTT assay. The release of protein displayed a spatiotemporal control model and its release in undesired direction was lessened. The bFGF maintained the bioactivities after release from the membranes. Moreover, different release amounts of bFGF from the different layers of the membrane induced significant difference in cell proliferation when the cells were seeded on the different layers of membrane in vitro. This kind of double-layered collagen membrane could have potential applications in the field of tissue repair due to the spatiotemporal control over growth factor delivery, the mild fabrication conditions, and the simple processes. PMID- 22083845 TI - Are anchoring vignettes ratings sensitive to vignette age and sex? AB - Anchoring vignettes are commonly used to study and correct for differential item functioning and response bias in subjective survey questions. Self-assessed health status is a leading example. A crucial assumption of the vignette methodology is 'vignette equivalence': The health status of the person described in the vignette must be perceived by all respondents in the same way. We use data from a survey experiment conducted with a sample of almost 5000 older Americans to validate this assumption. We find weak evidence that respondents' vignette ratings may be sensitive to the sex and, for older respondents, also to the age (implied by the first name) of the person described in the vignette. Our findings suggest that vignette equivalence may not hold, at least if the potentially subtle connotations of vignette persons' names are not fully controlled. PMID- 22083846 TI - Effect of micro-oxygenation on sensory characteristics and consumer preference of Cabernet Sauvignon wine. AB - BACKGROUND: The main objective of this study was to improve the structure of a Cabernet Sauvignon red wine in a short period of time by micro-oxygenation (MOX) at high rates (25 and 50 mL L(-1) month(-1) ), the effects of which were evaluated based on sensory characteristics and consumer preference. Sensory data were analysed by principal component analysis, discriminant analysis and ordinal logistic regression (OLR). RESULTS: MOX led to significant differences in the colour, colour stability and phenolic compounds of wine. Sensory characteristics also changed through MOX treatment, and wine experts were able to discriminate between MOX-treated and untreated samples, with olfactory intensity, complexity, astringency and roundness being the main discriminating characteristics. Ordinal logistic regression enabled identification of the sensory characteristics that drove consumer preference. CONCLUSION: MOX at high rates improved the sensory characteristics of wine and may therefore be considered a valid technique for obtaining structured wines in a short period of time, i.e. within just a few months after the vintage. The results highlight the need for (i) careful selection of the MOX dosage rate and duration (the 25 mL L(-1) month(-1) dose for 6 days provided the best result) and (ii) continuous monitoring of the MOX treatment. PMID- 22083848 TI - The influence of movement on the localization precision of sub-resolution particles in fluorescence microscopy. AB - Obtaining sub-resolution particle positions in fluorescence microscopy images is essential for single particle tracking and high-resolution localization microscopy. While the localization precision of stationary single molecules or particles is well understood, the influence of particle motion during image acquisition has been largely neglected. Here, we address this issue and provide a theoretical description on how particle motion influences the centroid localization precision, both in case of 2-D and 3-D diffusion. In addition, a novel method is proposed, based on dual-channel imaging, for the experimental determination of the localization precision of moving particles. For typical single particle tracking experiments, we show that the localization precision is approximately two-fold worse than expected from the stationary theory. Strikingly, we find that the most popular localization method, based on the fitting of a Gaussian distribution, breaks down for lateral diffusion. Instead, the centroid localization method is found to perform well under all conditions. PMID- 22083847 TI - Solvent exposures and Parkinson disease risk in twins. AB - OBJECTIVE: Several case reports have linked solvent exposure to Parkinson disease (PD), but few studies have assessed associations with specific agents using an analytic epidemiologic design. We tested the hypothesis that exposure to specific solvents is associated with PD risk using a discordant twin pair design. METHODS: Ninety-nine twin pairs discordant for PD ascertained from the National Academy of Sciences/National Research Council World War II Veteran Twins Cohort were interviewed regarding lifetime occupations and hobbies using detailed job task specific questionnaires. Exposures to 6 specific solvents selected a priori were estimated by expert raters unaware of case status. RESULTS: Ever exposure to trichloroethylene (TCE) was associated with significantly increased risk of PD (odds ratio [OR], 6.1; 95% confidence interval [CI] 1.2-33; p = 0.034), and exposure to perchloroethylene (PERC) and carbon tetrachloride (CCl(4) ) tended toward significance (respectively: OR, 10.5; 95% CI, 0.97-113; p = 0.053; OR, 2.3; 95% CI, 0.9-6.1; p = 0.088). Results were similar for estimates of exposure duration and cumulative lifetime exposure. INTERPRETATION: Exposure to specific solvents may increase risk of PD. TCE is the most common organic contaminant in groundwater, and PERC and CCl(4) are also ubiquitous in the environment. Our findings require replication in other populations with well-characterized exposures, but the potential public health implications are substantial. PMID- 22083849 TI - One-step method for isolation and purification of native beta-lactoglobulin from bovine whey. AB - BACKGROUND: The major whey protein beta-lactoglobulin (BLG) has been widely studied for its functional properties. The aim of this study was to develop an efficient, inexpensive and rapid one-step method for the isolation and purification of BLG while preserving its native structure. RESULTS: BLG was purified from defatted whey obtained from raw cow's milk by anion exchange chromatography. Protein purity and identity were determined using reverse phase high-performance liquid chromatography and mass spectrometry. Total BLG yield was 80% with protein purity from 97 to 99%. BLG isoforms A and B were separated into fractions of 91 and 99% purity respectively. The structure and native conformation of the isolated BLG were compared with those of standard commercial BLG by circular dichroism spectrometry, susceptibility to various crosslinking enzymes and enzyme-linked immunosorbent assay inhibition. CONCLUSION: The proposed method is very useful for the rapid preparation of BLG suitable for studying antigenic and molecular characteristics of this protein, as well as the effect of food processing on these properties. The procedure requires only 1 day for the purification of about 300 mg of BLG from a single run using a small column (2.5 cm * 20 cm) of diethylaminoethyl Sephadex and has potential for scaling up. PMID- 22083850 TI - Design and photophysical properties of zinc(II) porphyrin-containing dendrons linked to a central artificial special pair. AB - The click chemistry synthesis and photophysical properties, notably photo-induced energy and electron transfers between the central core and the peripheral chromophores of a series of artificial special pair-dendron systems (dendron = G1, G2, G3; Gx = zinc(II) tetra-meso-arylporphyrin-containing polyimides) built upon a central core of dimethylxanthenebis(metal(II) porphyrin) (metal = zinc, copper), are reported. The dendrons act as singlet and triplet energy acceptors or donors, depending on the dendrimeric systems. The presence of the paramagnetic d(9) copper(II) in the dendrimers promotes singlet-triplet energy transfer from the zinc(II) tetra-meso-arylporphyrin to the bis(copper(II) porphyrin) unit and slow triplet-triplet energy transfer from the central bis(copper(II) porphyrin) fragment to the peripheral zinc(II) tetra-meso-arylporphyrin. If bis(zinc(II) porphyrin) is the central core, evidence for chain folding is observed; this is unambiguously demonstrated by the presence of triplet-triplet energy transfer in the heterobimetallic systems, a process that can only occur at short distances. PMID- 22083851 TI - Endoscopic endonasal removal of laterally extended clival chordoma using side viewing scopes. AB - BACKGROUND: The transsphenoidal approach provides a straight and direct route to the clival chordoma, but has limitations for removing the tumor compartment extending laterally into the space posterior to the paraclival internal carotid artery. To overcome the limitations, a side-viewing endoscope and malleable/steerable instruments were employed. METHODS: Four clinical cases with clival chordoma extending into the retro-carotid space were analyzed for extent of resection, complications and clinical outcome. FINDINGS: The retro-carotid tumor compartment was removed in all cases under 30- and 70-degree side-viewing endoscopes using a malleable dissector and/or steerable forceps, resulting in gross total removal of the entire tumor. Single cases were complicated by transient abducens nerve palsy and cerebrospinal fluid leakage, which required surgical revision. All patients have been symptom free without tumor recurrence during the mean postoperative follow-up of 21.3 months. CONCLUSIONS: Though a longer follow-up is needed to evaluate its effectiveness in long-term tumor control, the surgical maneuver using the side-viewing endoscope is effective for removing laterally extended clival chordomas. PMID- 22083852 TI - Secondary normal pressure hydrocephalus in a patient with isolated frontal dilatation--an insight into pathophysiology? AB - Current theories of the pathophysiology of normal pressure hydrocephalus suggest the classical symptoms are a consequence of disruption of normal frontal function. We present the case of a 70-year-old patient with an isolated, frontal dilatation of his lateral ventricles in the presence of a complete triad as supportive of these theories. PMID- 22083854 TI - Cobalt-catalyzed coupling of alkyl iodides with alkenes: deprotonation of hydridocobalt enables turnover. PMID- 22083856 TI - ToF-SIMS analysis of chemical heterogenities in inkjet micro-array printed drug/polymer formulations. AB - Three different formulations comprising two drugs, felodipine and hydrochlorothiazide (HCT) and two polymers, poly(vinyl pyrolidone) (PVP) and poly(lactic-co-glycolic acid) (PLGA) were inkjet printed as micro-dot arrays and analysed on an individual micro-spot basis by time-of-flight secondary ion mass spectrometry (ToF-SIMS). For the HCT/PLGA formulation, the spots showed heterogeneity of the drug and other chemical constituents. To further investigate these heterogeneities, multivariate curve resolution was applied to the ToF-SIMS hyperspectral image datasets. This approach successfully identified distinct chemical components elucidating the HCT, PLGA, substrate material, and contaminants based on sulphur, phosphorous and sodium chloride. Spots printed using either of the drugs with PVP exhibited full substrate coverage and a uniform distribution of the active ingredient along with all other constituents within the printed spot area. This represents the preferred situation in terms of stability and controlling the release of a drug from a polymer matrix. PMID- 22083857 TI - A combined chitosan/nano-size hydroxyapatite system for the controlled release of icariin. AB - Icariin, a plant-derived flavonol glycoside, has been proved as an osteoinductive agent for bone regeneration. For this reason, we developed an icariin-loaded chitosan/nano-sized hydroxyapatite (IC-CS/HA) system which controls the release kinetics of icariin to enhance bone repairing. First, by Fourier transform infrared spectroscopy, we found that icariin was stable in the system developed without undergoing any chemical changes. On the other hand, X-ray diffraction, scanning electron microscopy and mechanical test revealed that the introduction of icariin did not remarkably change the phase, morphology, porosity and mechanical strength of the CS/HA composite. Then the hydrolytic degradation and drug release kinetics in vitro were investigated by incubation in phosphate buffered saline solution. The results indicated that the icariin was released in a temporally controlled manner and the release kinetics could be governed by degradation of both chitosan and hydroxyapatite matrix. Finally the in vitro bioactivity assay revealed that the loaded icariin was biologically active as evidenced by stimulation of bone marrow derived stroma cell alkaline phosphatase activity and formation of mineralized nodules. This successful IC-CS/HA system offers a new delivery method of osteoinductive agents and a useful scaffold design for bone regeneration. PMID- 22083858 TI - [Treatment related swallowing dysfunction and the potentialities of IMRT]. AB - Altered fractionated radiotherapy and concurrent chemoradiation could improve local control and survival for patients with locally advanced head and neck cancer. However, intensified treatment seems to increase late toxicity. Late swallowing dysfunction is common and has a large impact on quality of life and can get life-threatening character. Recent studies could show interrelations between the radiation dose to certain anatomical structures involved in the swallowing process and the risk of swallowing dysfunction. Important structures seem to be the pharyngeal constrictors and the supraglottic and glottic larynx. Further prospective clinical validations using standardized diagnostic protocols for dysphagia are necessary to establish dose constraints to anatomical structures involved in swallowing. PMID- 22083860 TI - [Prognosis of surgically treated primary parotid gland cancer - an evaluation of 231 cases]. AB - We present our results on the prognosis of parotid gland cancer with the help of a group of patients who were treated in a standardised manner and received a long term follow-up.We retrospectively analysed the clinicopathological data of 231 patients with a surgically treated primary parotid gland cancer and calculated survival parameters. The mean follow-up time was 52 months.The 5- and 10-year overall survival rate was 74.2% and 66.9%. 70 patients got a locoregional recurrence, 18.6% of those even after more than 5 years. Initial facial nerve palsy was a significant negative prognostic indicator for the disease-free survival. The most frequent histological subtypes could be divided into 3 prognostic groups with significant differences in the survival. The pathological tumour stage was a prognostic indicator for a worse overall and disease-free survival. The pT-stage, the pN-stage and the existence of distant metastases were independent prognostic factors.The group of patients is mainly characterised by the large size, the standardised therapy and the long follow-up time. We could show that the facial nerve palsy is a severe negative prognostic factor. For practical purpose, the classification into 3 histological subgroups seemed to be of great help. This should be considered in patient follow-up. Due to the amount of late recurrences, we propose a follow-up time longer than 5 years. We propose standardized surgery including total parotidectomy in combination with neck dissection. PMID- 22083861 TI - [Evaluation of the Dresden Tympanoplasty Model (DTM)]. AB - The training of microsurgical motor skills is essentiell for surgical education if the interests of the patient are to be safeguarded. In otosurgery the complex anatomy of the temporal bone and variations necessitate a special training before performing surgery on a patient. We therefore developed and evaluated a simplified middle ear model for acquiring first microsurgical skills in tympanoplasty.The simplified tympanoplasty model consists of the outer ear canal and a tympanic cavity. A stapes model is placed in projection of the upper posterior tympanic membrane quadrant at the medial wall of the simulated tympanic cavity. To imitate the annular ligament flexibility the stapes is fixed on a soft plastic pad. 41 subjects evaluated the model's anatomical analogy, the comparability to the real surgical situation and the general model properties the using a special questionnaire.The tympanoplasty model was very well evaluated by all participants. It is a reasonably priced model and a useful tool in microsurgical skills training. Thereby, it closes the gap between theoretical training and real operation conditions. PMID- 22083862 TI - [Recurrent periorbital swelling - intraorbital foreign body]. PMID- 22083863 TI - [A dubious middle ear trauma]. PMID- 22083864 TI - [From the expert's office: a new grading table for the reduction in earning capacity for the occupational cancer of larynx]. PMID- 22083865 TI - Knowledge, attitude and behaviour of the University of Ibadan women towards cancer of the cervix and its prevention. AB - OBJECTIVES: The two commonest cancers in Nigerian women are cancers of the breast and the cervix. Cancer of the cervix is the second commonest cancer and is a killer disease worldwide. The main objective of this study is to find out the knowledge, attitude and practices of the female university staff towards cancer of the cervix as a leadership group in the local effort towards cancer prevention. METHODOLOGY: A sample of 302 female staff of the University of Ibadan, which comprised 151 academic and 151 non-academic staff was studied. These were all the female members of staff who were met during the study visitation of all the departments on the main campus of the university and who were willing to participate in the study. A self-constructed and validated instrument called the knowledge, attitude and practice towards cervical cancer scale was used in collecting data for the study. RESULTS: Two hundred and forty two (79.1%) were aware of the disease, whereas 19.9% (60) were not aware. The academic staff were statistically significantly more knowledgeable of cervical cancer than the non-academic staff (p = 0.05). Two hundred and thirty-two (232 or 76.82%) have a positive attitude towards preventive measures for cancer of the cervix such as Pap smear or ascetic acid test. However, as much as 210 (73.5%) of the women had never undertaken a Pap smear or other screening test for the condition. CONCLUSION: There is need for more education and promotion of cancer screening and services in this locality. PMID- 22083866 TI - Accelerating progress at contaminated sediment sites: moving from guidance to practice. AB - Contaminated sediments are a pervasive problem in the United States. Significant economic, ecological, and social issues are intertwined in addressing the nation's contaminated sediment problem. Managing contaminated sediments has become increasingly resource intensive, with some investigations costing tens of millions of dollars and the majority of remediation projects proceeding at a slow pace. At present, the approaches typically used to investigate, evaluate, and remediate contaminated sediment sites in the United States have largely fallen short of producing timely, risk-based, cost-effective, long-term solutions. With the purpose of identifying opportunities for accelerating progress at contaminated sediment sites, the US Army Corps of Engineers-Engineer Research and Development Center and the Sediment Management Work Group convened a workshop with experienced experts from government, industry, consulting, and academia. Workshop participants identified 5 actions that, if implemented, would accelerate the progress and increase the effectiveness of risk management at contaminated sediment sites. These actions included: 1) development of a detailed and explicit project vision and accompanying objectives, achievable short-term and long-term goals, and metrics of remedy success at the outset of a project, with refinement occurring as needed throughout the duration of the project; 2) strategic engagement of stakeholders in a more direct and meaningful process; 3) optimization of risk reduction, risk management processes, and remedy selection addressing 2 important elements: a) the deliberate use of early action remedies, where appropriate, to accelerate risk reduction; and b) the systematic and sequential development of a suite of actions applicable to the ultimate remedy, starting with monitored natural recovery and adding engineering actions as needed to satisfy the project's objectives; 4) an incentive process that encourages and rewards risk reduction; and 5) pursuit of sediment remediation projects as a public-private collaborative enterprise. These 5 actions provide a clear path for connecting current US regulatory guidance to improved practices that produce better applications of science and risk management and more effective and efficient solutions at contaminated sediment sites. PMID- 22083868 TI - Exploring iron-based multifunctional catalysts for Fischer-Tropsch synthesis: a review. AB - The continuous increase in oil prices together with an increase in carbon dioxide concentration in the atmosphere has prompted an increased interest in the production of liquid fuels from non-petroleum sources to ensure the continuation of our worldwide demands while maximizing CO(2) utilization. In this sense, the Fischer-Tropsch (FT) technology provides a feasible option to render high value added hydrocarbons. Alternative sources, such as biomass or coal, offer a real possibility to realize these purposes by making use of H(2)-deficient or CO(2) rich syngas feeds. The management of such feeds ideally relies on the use of iron catalysts, which exhibit the unique ability to adjust the H(2)/CO molar ratio to an optimum value for hydrocarbon synthesis through the water-gas-shift reaction. Taking advantage of the emerging attention to hybrid FT-synthesis catalysts based on cobalt and their associated benefits, an overview of the current state of literature in the field of iron-based multifunctional catalysts is presented. Of particular interest is the use of zeolites in combination with a FT catalyst in a one-stage operation, herein named multifunctional, which offer key opportunities in the modification of desired product distributions and selectivity, to eventually overcome the quality limitations of the fuels prepared under intrinsic FT conditions. This review focuses on promising research activities addressing the conversion of syngas to liquid fuels mediated by iron-based multifunctional materials, highlights their preparation and properties, and discusses their implication and challenges in the area of carbon utilization through H(2)/CO(+CO(2)) mixtures. PMID- 22083869 TI - Hydrogen sorption from the Mg(NH2)2-KH system and synthesis of an amide-imide complex of KMg(NH)(NH2). AB - The interaction between KH and Mg(NH(2))(2) is investigated. Results from temperature-programmed desorption measurements on samples of [Mg(NH(2))(2)][KH](x) (x=0.5, 1.0, and 2.0) indicated that dehydrogenation from [Mg(NH(2))(2)][KH] occurred through a two-step reaction with an onset temperature as low as 60 degrees C. Accompanied by hydrogen release, K(2)Mg(NH(2))(4) and MgNH successively developed at lower temperatures, whereas KMg(NH)(NH(2)) developed at higher temperatures. However, when dehydrogenation was conducted under isothermal and near-equilibrium conditions, a single-step reaction that led to the formation of KMg(NH)(NH(2)) was observed. KMg(NH)(NH(2)) is a new amide imide complex. The synthesis of KMg(NH)(NH(2)) can be achieved either by dehydrogenation of the [Mg(NH(2))(2)][KH] mixture or by thermal decomposition of the [K(2)Mg(NH(2))(4)][Mg(NH(2))(2)] mixture. PMID- 22083870 TI - Remarkable uptake of CO2 and CH4 by graphene-Like borocarbonitrides, BxCyNz. AB - The surface areas and uptake of CO(2) and CH(4) by four graphene samples are measured and compared with activated charcoal. The surface areas are in the range of 5-640 m(2) g(-1), whereas the CO(2) and CH(4) uptake values are in the range of 18-45 wt % (at 195 K, 0.1 MPa) and 0-2.8 wt % (at 273 K, 5 MPa), respectively. The CO(2) and CH(4) uptake values of the graphene samples vary linearly with the surface area. In contrast, graphene-like B(x)C(y)N(z) samples with compositions close to BC(2)N exhibit surface areas in the range of 1500-1990 m(2) g(-1) and CO(2) and CH(4) uptake values in the ranges 97-128 wt % (at 195 K, 0.1 MPa) and 7.5-17.3 wt %, respectively. The uptake of these gases varies exponentially with the surface area of the B(x)C(y)Z(n) samples, and the uptake of CH(4) varies proportionally with that of CO(2). The uptake of CO(2) for the best BC(2)N sample is 64 wt % at 298 K. The large uptake of both CO(2) and CH(4) gases by BC(2)N betters the performance of graphenes and activated charcoal. First-principles calculations show that the adsorption of CO(2) and CH(4) is more favored on BCN samples compared to graphene. PMID- 22083872 TI - Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. AB - BACKGROUND: Oral carcinoma is an important malignancy throughout the world. MicroRNAs (miRNAs) are endogenously expressed, non-coding RNAs that regulate post transcriptional levels of targeted mRNAs. MiRNA-31(miR-31) is significantly upregulated in oral carcinoma tissues and plays oncogenic roles in oral carcinogenesis. METHODS: We analyzed the levels of miR-31 in saliva of patients with oral carcinoma (n = 45), oral verrucous leukoplakia (n = 10), and control healthy individuals (n = 24) by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Salivary miR-31 was significantly increased in patients with oral carcinoma at all clinical stages, including very small tumors. However, our preliminary analysis showed no increase of salivary miR-31 in patients with oral verrucous leukoplakia relative to controls. The miR-31 was more abundant in saliva than in plasma, suggesting salivary miR-31 was a more sensitive marker for oral malignancy. After excision of oral carcinoma, salivary miR-31 was remarkably reduced, indicating that most of the upregulated salivary miR-31 came from tumor tissues. CONCLUSION: Our results point to a potential application of salivary miR-31 as a biomarker for early detection and postoperative follow-up of oral carcinoma. PMID- 22083873 TI - Pharmacist intervention in primary care to improve outcomes in patients with left ventricular systolic dysfunction. AB - BACKGROUND: Meta-analysis of small trials suggests that pharmacist-led collaborative review and revision of medical treatment may improve outcomes in heart failure. METHODS AND RESULTS: We studied patients with left ventricular systolic dysfunction in a cluster-randomized controlled, event driven, trial in primary care. We allocated 87 practices (1090 patients) to pharmacist intervention and 87 practices (1074 patients) to usual care. The intervention was delivered by non-specialist pharmacists working with family doctors to optimize medical treatment. The primary outcome was a composite of death or hospital admission for worsening heart failure. This trial is registered, number ISRCTN70118765. The median follow-up was 4.7 years. At baseline, 86% of patients in both groups were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. In patients not receiving one or other of these medications, or receiving less than the recommended dose, treatment was started, or the dose increased, in 33.1% of patients in the intervention group and in 18.5% of the usual care group [odds ratio (OR) 2.26, 95% CI 1.64-3.10; P< 0.001]. At baseline, 62% of each group were treated with a beta-blocker and the proportions starting or having an increase in the dose were 17.9% in the intervention group and 11.1% in the usual care group (OR 1.76, 95% CI 1.31-2.35; P< 0.001). The primary outcome occurred in 35.8% of patients in the intervention group and 35.4% in the usual care group (hazard ratio 0.97, 95% CI 0.83-1.14; P = 0.72). There was no difference in any secondary outcome. CONCLUSION: A low intensity, pharmacist-led collaborative intervention in primary care resulted in modest improvements in prescribing of disease-modifying medications but did not improve clinical outcomes in a population that was relatively well treated at baseline. PMID- 22083874 TI - Composition of milk from minor dairy animals and buffalo breeds: a biodiversity perspective. AB - A comprehensive review is presented of the nutrient composition for buffalo, mare, and dromedary camel milks at the level of breed, and species-level data for yak, mithun, musk ox, donkey, Bactrian camel, llama, alpaca, reindeer and moose milks. Average values of nutrients were calculated and compared. Interspecies values (g 100 g-1) were 0.7-16.1 for total fat, 1.6-10.5 for protein, 2.6-6.6 for lactose, and 67.9-90.8 for water. Reindeer and moose milks had the highest fat and protein concentrations and the lowest lactose contents. Mare and donkey milks had the lowest protein and fat contents, in addition to showing the most appropriate fatty acid profile for human nutrition. Dromedary camel milk was most similar to cow milk in proximate composition. Moose milk was the richest in minerals, having values as high as 358 mg 100 g-1 for calcium, 158 mg 100 g-1 for sodium and 150 mg 100 g-1 for phosphorus. Interbreed differences of 4 g 100 g-1 were observed in total fat in buffalo, yak, mare and dromedary camel milks. Large interbreed differences were also present in the mineral contents in mare, buffalo and dromedary camel milks. By bringing together these compositional data, we hope to usefully widen the biodiversity knowledge base, which may contribute to the conservation and sustainable use of milk from underutilized dairy breeds and species, and to improved food and nutrition security, particularly in developing countries. PMID- 22083875 TI - N-(Imidazolidin-2-ylidene)-1-arylmethanamine oxides: synthesis, structure and pharmacological evaluation. AB - A high yielding three-step procedure was applied for the synthesis of N (imidazolidin-2-ylidene)-1-arylmethanamine oxides 3 (alpha-aminonitrones) starting from the easily accessible imidazolidin-2-one O-benzyl oxime 1. The alpha-aminonitrone-alpha-iminohydroxyloamine tautomerism of these products was studied theoretically and the structures of the synthesised compounds were confirmed by single crystal X-ray crystallographic analysis. The compounds were evaluated in vitro for their binding affinities to alpha(1) and alpha(2) adrenoceptors as well as imidazoline I(1) and I(2) receptors. The highest potencies at the alpha(2) adrenergic receptors were observed for compounds bearing biphenyl (4h, K(i) = 9 nM) and naphthyl (4i, K(i) = 92 nM) moieties. Compounds 4h and 4i were further tested in vivo for their cardiovascular and sedative-hypnotic effects in rats. PMID- 22083876 TI - Lateral extension of pi conjugation along the bay regions of bisanthene through a Diels-Alder cycloaddition reaction. AB - Diels-Alder cycloaddition reactions at the bay regions of bisanthene (1) with dienophiles such as 1,4-naphthoquinone have been investigated. The products were submitted to nucleophilic addition followed by reductive aromatization reactions to afford the laterally extended bisanthene derivatives 2 and 3. Attempted synthesis of a larger expanded bisanthene 4 revealed an unexpected hydrogenation reaction at the last reductive aromatization step. Unusual Michael addition was observed on quinone 14, which was obtained by Diels-Alder reaction between 1 and 1,4-anthraquinone. Compounds 1-3 exhibited near-infrared (NIR) absorption and emission with high-to-moderate fluorescent quantum yields. Their structures and absorption spectra were studied by density function theory and non-planar twisted structures were calculated for 2 and 3. All compounds showed amphoteric redox behavior with multiple oxidation/reduction waves. Oxidative titration with SbCl(5) gave stable radical cations, and the process was followed by UV/Vis/NIR spectroscopic measurements. Their photostability was measured and correlated to their different geometries and electronic structures. PMID- 22083877 TI - [Editorial: Pharmazie in unserer Zeit 5/2011]. PMID- 22083878 TI - The presumed atypical chemokine receptor CXCR7 signals through G(i/o) proteins in primary rodent astrocytes and human glioma cells. AB - SDF-1/CXCL12 binds to the chemokine receptors, CXCR4 and CXCR7, and controls cell proliferation and migration during development, tumorigenesis, and inflammatory processes. It is currently assumed that CXCR7 would represent an atypical or scavenger chemokine receptor which modulates the function of CXCR4. Contrasting this view, we demonstrated recently that CXCR7 actively mediates SDF-1 signaling in primary astrocytes. Here, we provide evidence that CXCR7 affects astrocytic cell signaling and function through pertussis toxin-sensitive G(i/o) proteins. SDF-1-dependent activation of G(i/o) proteins and subsequent increases in intracellular Ca(2+) concentration persisted in primary rodent astrocytes with depleted expression of CXCR4, but were abolished in astrocytes with depleted expression of CXCR7. Moreover, CXCR7-mediated effects of SDF-1 on Erk and Akt signaling as well as on astrocytic proliferation and migration were all sensitive to pertussis toxin. Likewise, pertussis toxin abolished SDF-1-induced activation of Erk and Akt in CXCR7-only expressing human glioma cell lines. Finally, consistent with a ligand-biased function of CXCR7 in astrocytes, the alternate CXCR7 ligand, I-TAC/CXCL11, activated Erk and Akt through beta-arrestin. The demonstration that SDF-1-bound CXCR7 activates G(i/o) proteins in astrocytes could help to explain some discrepancies previously observed for the function of CXCR4 and CXCR7 in other cell types. PMID- 22083879 TI - The role of cytoplasmic nanospaces in smooth muscle cell Ca2+ signalling. AB - We address the importance of cytoplasmic nanospaces in Ca(2+) transport and signalling in smooth muscle cells and how quantitative modelling can shed significant light on the understanding of signalling mechanisms. Increasingly more convincing evidence supports the view that these nanospaces--nanometre-scale spaces between organellar membranes, hosting cell signalling machinery--are key to Ca(2+) signalling as much as Ca(2+) transporters and Ca(2+) storing organelles. Our research suggests that the origin of certain diseases is to be sought in the disruption of the proper functioning of cytoplasmic nanospaces. We begin with a historical perspective on the study of smooth muscle cell plasma membrane-sarcoplasmic reticulum nanospaces, including experimental evidence of their role in the generation of asynchronous Ca(2+) waves. We then summarize how stochastic modelling approaches have aided and guided our understanding of two basic functional steps leading to healthy smooth muscle cell contraction. We furthermore outline how more sophisticated and realistic quantitative stochastic modelling is now being employed not only to deepen our understanding but also to aid in the hypothesis generation for further experimental investigation. PMID- 22083880 TI - Al NMR: a novel NMR data processing program optimized for sparse sampling. AB - Sparse sampling in biomolecular multidimensional NMR offers increased acquisition speed and resolution and, if appropriate conditions are met, an increase in sensitivity. Sparse sampling of indirectly detected time domains combined with the direct truly multidimensional Fourier transform has elicited particular attention because of the ability to generate a final spectrum amenable to traditional analysis techniques. A number of sparse sampling schemes have been described including radial sampling, random sampling, concentric sampling and variations thereof. A fundamental feature of these sampling schemes is that the resulting time domain data array is not amenable to traditional Fourier transform based processing and phasing correction techniques. In addition, radial sampling approaches offer a number of advantages and capabilities that are also not accessible using standard NMR processing techniques. These include sensitivity enhancement, sub-matrix processing and determination of minimal sets of sampling angles. Here we describe a new software package (Al NMR) that enables these capabilities in the context of a general NMR data processing environment. PMID- 22083881 TI - Alteration of ictal and interictal perfusion in patients with paroxysmal kinesigenic dyskinesia. AB - Although previous cerebral blood flow studies have suggested that the basal ganglia or thalamus are involved in the pathogenesis of paroxysmal kinesigenic dyskinesia (PKD), the precise anatomic substrate or pathophysiological networks associated with PKD remain unclear. Here, ictal and interictal single photon emission computed tomography (SPECT) in 2 patients with idiopathic PKD compared to 6 age-matched normal controls and the perfusion findings of subtraction ictal SPECT co-registered to MRI (SISCOM) in 1 patient are reported. The interictal and ictal perfusion changes were different in each of the patients and there were no consistent anatomic substrates observed. 2 patients had significant perfusion changes in the left frontal/temporal cortices compared to controls, whereas the others showed an increased uptake of 99mTc-ethyl cysteinate dimer (ECD) in the left occipital area on subtraction SPECT imaging. The results of this study suggest that the pathophysiology of PKD cannot be simply explained by lesions of the basal ganglia or thalamus, and that other associated areas of the cortex are likely involved in these movement disorders. PMID- 22083882 TI - Complicated pneumococcal meningitis in a fully vaccinated child: value of magnetic resonance imaging monitoring. AB - We present a unique case of life-threatening pneumococcal meningitis complicated by vasculitis in a fully vaccinated 4-year-old female with the heptavalent conjugate vaccine for Streptococcus pneumoniae (PCV7). Serotype 23F was isolated in both blood and cerebral spinal fluid (CSF) samples. Pulses of methylprednisolone were promptly initiated in addition to antibiotics leading to a good recovery. CSF studies and magnetic resonance imaging (MRI) of the brain were used for diagnosis and monitoring the response to corticoid therapy. We report the investigations of a child with failure of PCV7 vaccine to protect against vaccine-serotype invasive disease. Use of corticosteroids and temporal association with changes in brain imaging are described for the first time in literature. PMID- 22083884 TI - Barcoded nucleotides. PMID- 22083883 TI - Molecular interactions between glycopeptide vancomycin and bacterial cell wall peptide analogues. AB - The molecular interactions of the glycopeptide antibiotic vancomycin (Van) with bacterial cell wall analogues N,N'-diacetyl-L-Lys-D-Ala-D-Ala (Ac(2) KdAdA) and N,N'-diacetyl-L-Lys-D-Ala-D-Lac (Ac(2) KdAdL) were investigated in neat water, phosphate buffer and HEPES buffer by using fluorescence correlation spectroscopy (FCS) and molecular dynamics (MD) simulations. The FCS determined dissociation constants (k(d)) show that the intrinsic binding affinity between Van and the drug-sensitive peptide ligand Ac(2)KdAdA remains invariant when the solvent is changed from neat water to either PBS or HEPES buffer; this demonstrates that there are no obvious solvent effects on the association between Van and Ac(2)KdAdA due to the strong intermolecular interaction between the two moieties. When compared to Ac(2)KdAdA, a significantly larger k(d) value was observed for the binding between the drug-resistant peptide ligand Ac(2)KdAdL and Van. Furthermore, the k(d) increased by about 8- to 11-times when the solvent was changed from neat water to 10 mM phosphate/HEPES buffer. The stability of the Ac(2)KdAdL-Van complex was dependent on the concentration of the buffer and k(d) increases as the concentration of either phosphate ions or HEPES increased until an equilibrium was attained. Both FCS and MD simulation studies clearly showed that the components constituting the buffer solution (e.g., phosphate ions and HEPES) are involved in molecular interactions with the binding pocket of Van and they profoundly affect the intrinsic stability of the complex formed between the low-affinity Ac(2)KdAdL and Van. These results could help us to better understand the detailed structure and activity of glycopeptide antibiotic derivatives toward bacterial cell wall peptide analogues, and can further facilitate the development of new drug candidates against drug-resistant bacterial strains. PMID- 22083885 TI - Prevention of radiation-induced xerostomia by submandibular gland transfer. AB - BACKGROUND: This study was carried out for the purpose of evaluating the efficacy of submandibular gland transfer to prevent radiation-induced xerostomia. METHODS: Thirty-eight patients with oropharyngeal carcinoma were recruited. Twenty-six submandibular glands were transferred into the submental space to elude radiotherapy in 24 patients (transfer group); the submandibular gland was not disturbed in the control group (n = 14). The salivary flow rate, xerostomia, and quality of life (QOL) were assessed preoperatively, postoperatively, and after radiotherapy. The swallowing function was then evaluated after radiotherapy. RESULTS: All the transferred glands survived and functioned after radiotherapy. The submandibular salivary flow rate recovered by 6 months after radiotherapy in the transfer group, whereas the flow rate declined drastically after radiotherapy and remained at a low level in the longer term in the control group. Two years after radiotherapy, 92.3% of patients in the transfer group had no or minimal xerostomia. QOL in the transfer group was better than that in the control group from 3 months after radiotherapy. Histologically, the majority of the transferred glands had normal glandular acini and ducts. There was no significant difference in dysphagia between the groups. CONCLUSIONS: The submandibular gland can be successfully transferred to the submental space, thus preserving salivary function and preventing radiation-induced xerostomia. The transfer of the submandibular gland can improve the QOL by alleviating xerostomia, although it did not relieve dysphagia in this study. PMID- 22083887 TI - Optimal apheresis treatment volume for the efficacy and safety of leukocytapheresis with Cellsorba in patients with active ulcerative colitis. AB - BACKGROUND: Leukocytapheresis (LCAP) is used as an adjunct therapy for patients with active ulcerative colitis (UC). Although, LCAP is routinely performed at 3,000 mL per session, we were interested to see that if this can be replaced with bodyweight (BW) adjusted volume. METHODS: In an open label prospective trial, the clinical response to BW adjusted LCAP (BWA-LCAP) was evaluated in 14 patients with active UC. Fourteen demography matched UC patients who had been treated with the routine 3,000 mL LCAP were randomly sampled from our database as a control group. All patients were given 10 weekly LCAP sessions. In the BWA-LCAP group, the processed blood volume (PBV) was set at 30 mL/kg * BW/session. Baseline demographic measures were not significantly different between the two groups. RESULTS: The average PBV in the BWA-LCAP group was 1971.0 +/- 330.0 mL, range 1,020-2,460. In both groups, the average UC clinical disease activity index, the endoscopic index, and the concomitant prednisolone dosage were significantly and equally reduced during the course of 10 LCAP. Accordingly, at the end of the trial, no significant difference was seen in any outcome measure between the two groups. However, a significantly higher incidence of adverse event (AE) was observed in the routine 3,000 mL LCAP group as compared with the BWA-LCAP group (P < 0.01). CONCLUSIONS: The outcomes of this investigation showed that the therapeutic efficacy of LCAP based on 30 mL/kg * BW is similar to the routine 3,000 mL per session LCAP. However, BWA-LCAP should be favored if one is to see the full potential of LCAP without AE. PMID- 22083888 TI - Highly sensitive and specific detection of neonicotinoid insecticide imidacloprid in environmental and food samples by a polyclonal antibody-based enzyme-linked immunosorbent assay. AB - BACKGROUND: Imidacloprid is one of the main neonicotinoid insecticides widely used in agriculture owing its broad spectrum of activity and low bioaccumulation. However, imidacloprid is toxic to honey bees and other beneficial organisms, and its residues may occur in environmental and food samples, posing a potential hazard to consumers. In this study the imidacloprid derivative bearing a three atom length spacer was synthesized and coupled to carrier proteins. Highly sensitive and specific polyclonal antibodies against imidacloprid were successfully produced and the polyclonal antibody-based enzyme-linked immunosorbent assay (pAb-ELISA) was developed. RESULTS: The ELISA standard curve was constructed within the concentration range 0.1-100 ng mL(-1). The IC(50) value for nine standard curves was in the range 1.2-3.0 ng mL(-1) and the limit of detection was 0.03-0.16 ng mL(-1). The sensitivity of the assay was one order of magnitude higher than that in most published papers. There was almost no cross reactivity of the antibody with four structurally related compounds (acetamiprid, nicotine, clothianidin and nitenpyram) and six other compounds, indicating that the assay displays not only high sensitivity but also high specificity. No detectable imidacloprid was found in 11 collected environmental and food samples by the assay. For imidacloprid-spiked samples, acceptable recoveries of 73.4 94.4% and intra-assay coefficients of variation of 2.2-12.8% were obtained. The assay was also validated with high-performance liquid chromatography (HPLC) and a good correlation of ELISA with HPLC was achieved. CONCLUSION: The proposed ELISA provides a sensitive, specific, simple and cost-effective quantitative/screening method for detecting imidacloprid in environmental and food samples. PMID- 22083890 TI - Interaction of hesperetin glucuronide conjugates with human BCRP, MRP2 and MRP3 as detected in membrane vesicles of overexpressing baculovirus-infected Sf9 cells. AB - The citrus flavonoid hesperetin (4'-methoxy-3',5,7-trihydroxyflavanone) is the aglycone of hesperidin, the major flavonoid present in sweet oranges. Hesperetin 7-O-glucuronide (H7G) and hesperetin 3'-O-glucuronide (H3'G) are the two most abundant metabolites of hesperetin in vivo. In this study, their interaction with specific ABC transporters, believed to play a role in the disposition and bioavailability of hesperetin, was studied using Sf9 membranes from cells overexpressing human BCRP (ABCG2), MRP2 (ABCC2) and MRP3 (ABCC3). Both H7G and H3'G were tested for their potential to activate and inhibit ATPase activity, and to inhibit vesicular transport by these transporters. Both H7G and H3'G demonstrated interaction with all tested ABC transporters, especially with BCRP and MRP3. An interesting difference between H7G and H3'G was seen with respect to the interaction with BCRP: H7G stimulated the ATPase activity of BCRP up to 76% of the maximal effect generated by the reference activator sulfasalazine, with an EC(50) of 0.45 uM, suggesting that H7G is a high affinity substrate of BCRP, whereas H3'G did not stimulate BCRP ATPase activity. Only moderate inhibition of BCRP ATPase activity at high H3'G concentrations was observed. This study provides information on the potential of hesperetin glucuronide conjugates to act as specific ABC transporter substrates or inhibitors and indicates that regio specific glucuronidation could affect the disposition of hesperetin. PMID- 22083891 TI - Chiral self-assembled solid microspheres: a novel multifunctional microphotonic device. AB - Solid chiral microspheres with unique and multifunctional optical properties are produced from cholesteric liquid crystal-water emulsions using photopolymerization processes. These self-organizing microspheres exhibit different internal configurations of helicoidal structures with radial, conical or cylindrical geometries, depending on the physicochemical characteristics of the precursor liquid crystal emulsion. PMID- 22083892 TI - Tissue transglutaminase, inflammation, and cancer: how intimate is the relationship? AB - Despite significant advances in surgery and biology, cancer remains a major health problem. It is now well accepted that metastasis and cancer cells' acquired or inherent resistance to conventional therapies are major roadblocks to successful treatment. Chronic inflammation is an important driving force that provides a favorable platform for cancer's progression and development and suggests a link between inflammation and metastatic transformation. However, how chronic inflammation contributes to metastatic cell transformation is not well understood. According to the current theory of cancer progression, a small subpopulation of cancer stem cells (CSCs) in tumors is responsible for their metastasis, resistance, and sustenance. Whether CSCs originate from normal stem cells or from dedifferentiation of terminally differentiated cells remains unknown. Recent evidence indicates that stem cells are not unique; malignant or nonmalignant cells can reprogram and de-differentiate to acquire a stemness phenotype. Thus, phenotypic plasticity may exist between stem cells and non-stem cells, and a dynamic equilibrium may exist between the two phenotypes. Moreover, this equilibrium may shift in one direction or another on the basis of contextual signals in the microenvironment that influence the interconversion between stem and non-stem cell compartments. Whether the inflammatory microenvironment influences this interconversion and shifts the dynamic equilibrium towards stem cell compartments remains unknown. We recently found that aberrant tissue transglutaminase (TG2) expression induces the mesenchymal transition (EMT) and stem cell characteristics in epithelial cells. This finding, in conjunction with the observation that inflammatory signals (e.g., TGFbeta, TNFalpha, and NF kappaB) which induce EMT, also induce TG2 expression, suggests a possible link between TG2, inflammation, and cancer progression. In this review, we summarize TG2-driven processes in inflammation and their implications in cancer progression. PMID- 22083893 TI - Involvement of AtoSC two-component system in Escherichia coli flagellar regulon. AB - The AtoSC two-component system in Escherichia coli is a key regulator of many physiological processes. We report here the contribution of AtoSC in E. coli motility and chemotaxis. AtoSC locus deletion in DeltaatoSC cells renders cells not motile or responsive against any chemoattractant or repellent independently of the AtoSC inducer's presence. AtoSC expression through plasmid complemented the DeltaatoSC phenotype. Cells expressing either AtoS or AtoC demonstrated analogous motility and chemotactic phenotypes as DeltaatoSC cells, independently of AtoSC inducer's presence. Mutations of AtoC phosphate-acceptor sites diminished or abrogated E. coli chemotaxis. trAtoC, the AtoC constitutive active form which lacks its receiver domain, up-regulated E. coli motility. AtoSC enhanced the transcription of the flhDC and fliAZY operons and to a lesser extent of the flgBCDEFGHIJKL operon. The AtoSC-mediated regulation of motility and chemotactic response required also the expression of the CheAY system. The AtoSC inducers enhanced the AtoSC-mediated motility and chemotaxis. Acetoacetate or spermidine further promoted the responses of only AtoSC-expressing cells, while Ca(2+) demonstrated its effects independently of AtoSC. Histamine regulated bacterial chemotaxis only in atoSC (+) cells in a concentration-dependent manner while reversed the AtoSC-mediated effects when added at high concentrations. The trAtoC-controlled motility effects were enhanced by acetoacetate or spermidine, but not by histamine. These data reveal that AtoSC system regulates the motility and chemotaxis of E. coli, participating in the transcriptional induction of the main promoters of the chemotactic regulon and modifying the motility and chemotactic phenotypes in an induction-dependent mechanism. PMID- 22083895 TI - Assessing the effectiveness of environmental enrichment in bottlenose dolphins (Tursiops truncatus). AB - Environmental enrichment is often used to improve well-being and reduce stereotyped behaviors in animals under human care. However, the use of objects to enrich animal environments should not be considered to be effective until its success has been scientifically demonstrated. This study was conducted at Asterix Park in France in April 2009. The study investigated the use of 21 familiar objects with a group of six bottlenose dolphins (Tursiops truncatus). The dolphin trainers introduced four different objects into the dolphin pool every day on a rotating basis. Using a focal-object sampling method, we collected and analyzed data from twenty-one 15 min sessions. The results revealed a positive correlation between interest behaviors and interactive behaviors. Some dolphins had "favorite toys". However, only 50% of objects elicited manipulative behaviors. These findings demonstrate that dolphins do not treat all objects provided to them as "toys". Behavioral changes in the animals subsequent to the introduction of objects do not necessarily indicate an enrichment effect of the objects; rather, the motivation for the dolphins' behaviors toward the objects must be investigated. The animals' behavior must be considered in light of the social context and of the animals' individual behavioral profiles. The relevance of a constructivist approach to evaluating the effectiveness of enrichment programs is discussed. PMID- 22083896 TI - Astragaloside IV and cycloastragenol stimulate the phosphorylation of extracellular signal-regulated protein kinase in multiple cell types. AB - Two Chinese herb-derived small molecule telomerase activators, astragaloside IV (AG-IV) and cycloastragenol (CAG), have recently been shown to improve the proliferative response of CD8+ T lymphocytes from HIV-infected patients by upregulating telomerase activity. Here, we examined the signaling mechanism of AG IV and CAG. Telomerase activity in human embryonic kidney HEK293 fibroblasts was increased upon treatment with increasing concentrations of AG-IV or CAG. Both compounds induced the phosphorylation of extracellular signal-regulated protein kinase (ERK) in a time- and dose-dependent manner in HEK293 cells and HEK-neo keratinocytes. AG-IV and CAG also stimulated ERK phosphorylation in other cell lines of lung, brain, mammary, endothelial, and hematopoietic origins. Use of selective inhibitors and dominant negative mutants revealed the involvement of c Src, MEK (ERK kinase), and epidermal growth factor receptor in CAG-induced ERK phosphorylation. Our data indicate that AG-IV and CAG may exert their cellular effects through the activation of the Src/MEK/ERK pathway. PMID- 22083897 TI - 20-OH-ecdysone prevents hot flushes in ovariectomized rats. AB - Hot flushes are due to the lack of estrogens and are the most characteristic climacteric complaints. Hormone replacement therapy was the standard treatment but now its use is limited because of side effects. Need therefore arises to search for non-estrogenic alternatives. The molting hormone 20-beta hydroxyecdysone (Ecd) is produced by several plants including spinach and has no estrogenic or androgenic properties but enhances GABAergic effects in neurons. Since GABAergic compounds can ameliorate hot flushes, we investigated the effects of Ecd on subcutaneous body temperature of intact and ovariectomized (ovx) rats. The subcutaneous body temperature was recorded at 5-min intervals over a period of 3 hours. Rats were then ovx, and skin temperatures were recorded after an acute intravenous (5 mg) and during subchronic and chronic oral application of Ecd (73 mg/animal/day). For additional control purposes, a group of ovx rats received food containing estradiol-17 beta (E2). Skin temperature in individual ovx animals fluctuated largely with peaks (hot flushes) occurring every 20-40 minutes. Following the i.v. treatment with Ecd, skin temperature dropped by more than 1 degrees C, an effect much larger than in the controls. One and two weeks later, hot flushes were only seen in ovx controls but not in intact, E2-, or Ecd treated animals. As a consequence, E2 and Ecd intake significantly (p < 0.05) reduced the mean temperature in ovx rats during the various time points of the study. These results suggest that Ecd is efficient to prevent hot flushes in ovx rats. PMID- 22083894 TI - Drosophila as a model for epithelial tube formation. AB - Epithelial tubular organs are essential for life in higher organisms and include the pancreas and other secretory organs that function as biological factories for the synthesis and delivery of secreted enzymes, hormones, and nutrients essential for tissue homeostasis and viability. The lungs, which are necessary for gas exchange, vocalization, and maintaining blood pH, are organized as highly branched tubular epithelia. Tubular organs include arteries, veins, and lymphatics, high-speed passageways for delivery and uptake of nutrients, liquids, gases, and immune cells. The kidneys and components of the reproductive system are also epithelial tubes. Both the heart and central nervous system of many vertebrates begin as epithelial tubes. Thus, it is not surprising that defects in tube formation and maintenance underlie many human diseases. Accordingly, a thorough understanding how tubes form and are maintained is essential to developing better diagnostics and therapeutics. Among the best-characterized tubular organs are the Drosophila salivary gland and trachea, organs whose relative simplicity have allowed for in depth analysis of gene function, yielding key mechanistic insight into tube initiation, remodeling and maintenance. Here, we review our current understanding of salivary gland and trachea formation - highlighting recent discoveries into how these organs attain their final form and function. PMID- 22083898 TI - Evaluation of the antibacterial activity of Chilean plants traditionally used for wound healing therapy against multidrug-resistant Staphylococcus aureus. AB - Anti-staphylococcal activity of Chilean medicinal plants traditionally used by the Huilliche people for wound healing therapy was evaluated against nine Staphylococcus aureus strains. Three extracts of 26 plant samples (20 species) were evaluated by agar overlay bioautography and MIC determination. Total phenolics and tannins were determined, and the antibacterial contribution of the latter was evaluated. The diffusion assay showed that 17 species were active against susceptible S. AUREUS and that 15 species were active against resistant S. aureus. Removal of tannins from extracts rendered only six species active. MIC determination showed that 20 extracts had antibacterial activity on all eight strains, and the most potent MIC value was 64 ug/mL. Remarkably, 37 extracts were active against the otherwise multidrug-resistant vanthida strain. Our findings support the wound healing properties of Huilliche medicinal plants and the hypothesis that these plants are promising sources of potential anti staphylococcal agents towards multidrug-resistant strains. PMID- 22083899 TI - Phosphodiesterase I-inhibiting Diels-Alder adducts from the leaves of Morus mesozygia. AB - A new 2-arylbenzofuran derivative, (+)-dimethylsmoracin O (1), and three new Diels-Alder type adducts, mesozygins A-C (2-4), in addition to eight known compounds, artonin I (5), chalcomaracin (6), norartocarpetin (7), moracin L (8), mulberrofuran F (9), moracin M (10), moracin C (11), and morachalcone A (12),were isolated from the leaves of Morus mesozygia Stapf. Structures were elucidated by spectroscopic data analyses. Compounds 2-7 displayed a potent phosphodiesterase I inhibitory activity. PMID- 22083900 TI - Metabolites of the mangrove fungus Xylaria sp. BL321 from the South China Sea. AB - Two new lactones, 1 and 2, together with five known compounds, 3-7, were isolated from the marine mangrove fungus Xylaria sp. BL321. Their structures were determined by comprehensive analysis of their MS and NMR spectroscopic data. The absolute configurations of 1 and 2 were established on the basis of electronic circular dichroism calculations. It was found that the exocyclic double bond of 1 rearranged into a cyclic double bond to form a new crystal compound (1a) in diluted NaOH solution. Compound 3 was isolated for the first time as a natural product; its absolute configuration was determined by single-crystal X-ray crystallography. Compounds 4-7 displayed cytotoxicity against human breast cancer cell lines MCF-7 and MDA-MB-435, while compounds 1- 3 were inactive (IC(50) > 50 uM). PMID- 22083901 TI - Comparison of the conductance of three types of porphyrin-based molecular wires: beta,meso,beta-fused tapes, meso-Butadiyne-linked and twisted meso-meso linked oligomers. AB - The length dependence of charge transport is evaluated in three families of porphyrin-based wires. Planar edge-fused tapes and alkyne-linked oligomers mediate efficient charge transport with exceptionally shallow distance dependence, whereas the conductances of the twisted singly linked chains decrease steeply with increasing oligomer length. The planar tapes are more conjugated than the alkyne-linked oligomers, but these two types of wires have similar conductance attenuation factors. PMID- 22083902 TI - 2,2'-Biphospholes: building blocks for tuning the HOMO-LUMO gap of pi-systems using covalent bonding and metal coordination. PMID- 22083903 TI - Indications for pedicled pectoralis major flap in a free tissue transfer practice. AB - BACKGROUND: The pedicled pectoralis major myocutaneous flap (PMMF) was highly used over the last 3 decades. The current era of free tissue transfer has gradually relegated the PMMF to a secondary role. METHODS: In a retrospective review of all patients undergoing pedicled PMMF from 2002 to now, we sought to determine the current role and assess the outcomes of the PMMF in a primary microvascular head and neck reconstructive center. RESULTS: Fifty-five PMMFs were performed in 53 patients (24 myocutaneous and 31 myofascial); group 1 consisted of 20 patients (38%) who underwent a secondary PMMF after a free flap complication (flap failure 9/20, fistula 5/20, wound breakdown with great vessel exposure 3/20, loss of soft tissue skin paddle 2/20, and delayed hematoma in 1/20); group 2 included 18 patients (33%) who had a simultaneous free flap with a PMMF for dead space filler or cervical skin/great vessel coverage reconstruction, whereas the remaining 15 patients (29%) in group 3 underwent primary PMMF for reconstruction of cervical skin defect, great vessel coverage, pharyngocutaneous fistula, infection, and dead space filler. Complications of PMMF included 3 hematomas, 2 partial dehiscences, 1 chest wall abscess, and 1 case of mastitis. Because of cervical tethering, 14 of 53 patients underwent secondary pectoralis myectomy with cervical contracture release at a mean of 10.3 months after initial surgery. CONCLUSION: The pedicled PMMF continues to serve an important role in head and neck reconstruction in the microvascular era with notable uses for free flap rescue, with simultaneous free flap reconstruction and for primary reconstruction in select circumstances with an overall acceptable short- and long term morbidity profile. PMID- 22083904 TI - Blue emitting 3pi-2spiro terfluorene-indenofluorene isomers: a structure properties relationship study. AB - Two novel terfluorenyl derivatives, 2,2'',7,7''-tetrakis(9,9-dioctyl-9H-fluoren-2 yl)dispiro[fluorene-9,11'-indeno-(2,1-a)-fluorene-12',9''-fluorene] ((2,1-a)-DST IF) and 2,2'',7,7''-tetrakis(9,9-dioctyl-9H-fluoren-2-yl)dispiro- [fluorene-9,6' indeno-(1,2-b)-fluorene-12',9''-fluorene] ((1,2-b)-DST-IF) have been synthesized by two different synthetic approaches. These terfluorenyl derivatives possess a different central indenofluorene core, namely (2,1-a)-indenofluorene or (1,2-b) indenofluorene, which imposes two distinct geometry profiles, and different structural environments for the terfluorenyl fluorophores that translates into drastically different optical and electrochemical properties for (2,1-a)-DST-IF and (1,2-b)-DST-IF. These properties have been carefully studied through a combined experimental and theoretical approach. The (2,1-a)-DST-IF isomer has been successfully used as emitting layer in a blue single-layer small-molecule organic light-emitting diode (SMOLED) and appears as the first example of a blue emission arising from intramolecular terfluorenyl excimers. Regarding the importance of terfluorenyl derivatives in organic electronics, the present structure-properties relationship study, may open new avenues in the design of efficient blue fluorophores. PMID- 22083905 TI - Osteoporosis Patient Treatment Satisfaction Questionnaire in postmenopausal women intermittently treated with oral bisphosphonates: the BRAVO study. AB - The Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q) is a psychometric measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The study was a multicenter, nationwide, cross-sectional, patient reported outcome study conducted to evaluate treatment satisfaction and quality of life using the OPSAT-Q in patients receiving oral bisphosphonate therapy. This study enrolled postmenopausal women from 43 hospitals and 112 clinics who had intermittently taken oral bisphosphonates for treatment of osteoporosis. 4,220 postmenopausal Korean women with a mean age of 65.3 years and a mean body mass index of 22.9 kg/m(2) participated in the study. All items within each subscale domain were more highly correlated with their hypothesized subscale domain relative to the other subscale domains, and all 16 items were significantly correlated with an overall composite satisfaction score (CSS). All scores showed acceptable internal consistency reliability (Cronbach's alpha >0.70, range 0.88 0.91). Comparisons of OPSAT-Q scores were made between selective subgroups of participants: monthly versus weekly administration, years of taking bisphosphonates, smoking habitus, acid-related medication and comorbid conditions. Mean OPSAT-Q subscale domains and CSS were higher for users of monthly bisphosphonates, with shorter duration, non-smokers, and non-users of acid-related medication. Mean OPSAT-Q subscale domain scores of side-effects were high for absence of comorbid conditions. The OPSAT-Q demonstrated acceptable measurement properties, including validity and reliability of subscale domains and CSS, in oriental women with postmenopausal osteoporosis. Postmenopausal women intermittently using oral bisphosphonate therapy reported increased satisfaction with monthly administration, with shorter duration, non-smokers, non-users of acid-related medication, and an absence of comorbid conditions. PMID- 22083906 TI - Asymptomatic Paget's bone disease in ethnic Thais: a series of four case reports and a review of the literature. AB - Paget's bone disease is quite common in some parts of Europe and countries inhabited by European emigrants, but it is rare in Asia. There have been only 13 reported cases in Southeast Asia, including one reported case from Thailand. Half of the previously reported cases had bone symptoms and the other half were asymptomatic, but were incidentally discovered when patients were being investigated for other medical problems. Here are reported cases of four asymptomatic patients who presented elevation of serum alkaline phosphatase during routine annual medical checkups. All patients were of Chinese descent and all cases were proven by biopsy. Based on this experience, we are of the opinion that a substantial number of unrecognized cases of Paget's disease exist among ethnic Thais. We feel that they would be revealed if clinicians were alerted of its presence and if they included it as a possible diagnosis together with metastasis and osteoporosis when examining bone lesions or when results for elevated serum alkaline phosphatase are detected during routine checkups. We also anticipate that a higher prevalence of this disease may occur in future Thai generations due to the addition of offspring from Asian-European intermarriages to offspring of Chinese descent in the ethnic Thai population. PMID- 22083907 TI - Triterpenoid saponins from the genus Camellia. PMID- 22083908 TI - Chemical constituents of plants from the genus Machilus. PMID- 22083909 TI - Chemical constituents of plants from the genus Trigonostemon. PMID- 22083910 TI - Historical variation of structural novelty in a natural product library. AB - To evaluate the potential of natural products as novel structure suppliers, a historical analysis was performed on the structural novelty of a natural product library, viz., the Chapman & Hall/CRC Dictionary of Natural Products. The results show that although the unexplored natural product universe is still ample, it is more and more difficult to find novel agents from nature, with the discovery probability of novel structures and scaffolds being lower than 50% in the near future, which mainly results from the intrinsic redundancy of natural products and, thus, is unlikely to be reversed merely through technical progresses. PMID- 22083911 TI - Chemical characterization and genetic relationships among Ocimum basilicum L. cultivars. AB - Twenty-seven Ocimum basilicum cultivars were subjected to a chemical characterization of essential oil components by gas chromatography/mass spectrometry (GC/MS) and a genetic characterization using the amplified fragment length polymorphism (AFLP) technique. Since the same 27 accessions had previously been classified into six morphotypes, these analyses allowed us to make detailed comparisons of chemistry, genetics, and morphology. The chemical composition and morphology of the studied cultivars appeared to have a strong genetic component. The AFLP analysis revealed a distinction between the green and purple morphotypes. The green morphotypes predominantly utilized the terpene biosynthetic pathway, while most purple morphotypes primarily utilized the phenylpropene biosynthetic pathway. The GC/MS analysis led to identification of 87 volatiles. Among the 27 cultivars, five chemotypes were identified. A detailed characterization of the essential oil constituents indicated the existence of both specific combinations of compounds and 'private' compounds with the potential to be used in many aspects of human life. The established relationship between a genetic profile, chemical composition, and morphology represents an important step in future breeding programs and in the cultivation of this species. PMID- 22083912 TI - Composition of the essential oils in various organs at different developmental stages of Ammi visnaga (L.) Lam. from Tunisia. AB - The composition of the essential oils isolated by hydrodistillation from various organs at different development stages of Ammi visnaga (L.) Lam. growing in Tunisia was determined by GC/MS analysis. In particular, the oil profiles of the leaves, stems, flower buds, roots, umbels, and fruits have been examined during the whole life cycle. The oil from the flowering aerial parts was characterized by a high content of isoamyl 2-methylbutanoate. After flowering and during desiccation and fructification, the umbels and fruits expressed a high content of linalool. The oils, extracted from the roots collected in the vegetatif, buds floral, and floral stages, were rich in monoterpene aldehydes, oxygenated monoterpenes, and monoterpene hydrocarbons. The highest level of non-terpene hydrocarbons was found at the flower-bud stage, represented by 61.3% of nonane. Among the monoterpenes, sabinene (12.5%) and beta-pinene (8.5%) were identified in the flower buds. PMID- 22083913 TI - Volatiles of Curcuma mangga Val. & Zijp (Zingiberaceae) from Malaysia. AB - Analysis by GC and GC/MS of the essential oil obtained from Malaysian Curcuma mangga Val. & Zijp (Zingiberaceae) rhizomes allowed the identification of 97 constituents, comprising 89.5% of the total oil composition. The major compounds were identified as myrcene (1; 46.5%) and beta-pinene (2; 14.6%). The chemical composition of this and additional 13 oils obtained from selected Curcuma L. taxa were compared using multivariate statistical analyses (agglomerative hierarchical cluster analysis and principal component analysis). The results of the statistical analyses of this particular data set pointed out that 1 could be potentially used as a valuable infrageneric chemotaxonomical marker for C. mangga. Moreover, it seems that C. mangga, C. xanthorrhiza Roxb., and C. longa L. are, with respect to the volatile secondary metabolites, closely related. In addition, comparison of the essential oil profiles revealed a potential influence of the environmental (geographical) factors, alongside with the genetic ones, on the production of volatile secondary metabolites in Curcuma taxa. PMID- 22083914 TI - New flavanones from the leaves of Cryptocarya chinensis and their antituberculosis activity. AB - Four new flavanones, cryptoflavanones A-D (1-4, resp.), together with eight known compounds, were isolated from the leaves of Cryptocarya chinensis. The structures of these new compounds were determined by spectral analyses. Among the isolated compounds, pinocembrin (5) and cryptocaryone (6) exhibited antituberculosis activity against Mycobacterium tuberculosis H(37) Rv strain in vitro with MIC values of 3.5 and 25.0 MUg/ml, respectively. PMID- 22083915 TI - Novel tirucallane-type triterpenoids from Aphanamixis grandifolia. AB - Phytochemical investigation on the stem bark of Aphanamixis grandifolia afforded five novel tirucallane-type triterpenoids, (13alpha,14beta,17alpha,23Z)-25 methoxy-21,23-epoxylanosta-7,20(22),23-triene-3,21-dione (1), (13alpha,14beta,17alpha,23Z)-21,23-epoxylanosta-7,20(22),23,25-tetraene-3,21 dione (2), (3R,5R, 9R,10R,13S,14S,17S)-17-{(2R,3S,5R)-5-[(2S)-3,3-dimethyloxiran 2-yl]-2,3,4,5-tetrahydro-2,5-dimethoxyfuran-3-yl}-4,4,10,13,14-pentamethyl 2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3 ol (3), (5R,9R,10R,13S,14S,17S)-17-{(2R,3S,5R)-5-[(2S)-3,3-dimethyloxiran-2-yl] 2,5-dimethoxytetrahydrofuran-3-yl}-1,2,4,5,6,9,10,11,12,13,14,15,16,17 tetradecahydro-4,4,10,13,14-pentamethyl-3H-cyclopenta[a]phenanthren-3-one (4), and (3alpha,13alpha,14beta,17alpha,20S,23R)-23-ethoxy-3-hydroxy-21,23-epoxylanost 7-en-24-one (5). The (1) H- and (13) C-NMR spectra of all compounds were fully assigned using a combination of 2D-NMR experiments, including HSQC, HMBC, and ROESY sequences. The structure of 1 with the absolute configuration was determined by ECD calculation. Compounds 3 and 4 showed moderate activities against human MCF-7 and HeLa cancer cells. PMID- 22083916 TI - Synthesis of (glycopyranosyl-triazolyl)-purines and their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B). AB - Development of novel purine derivatives has attracted considerable interest, since both purine and purine-based nucleosides display a wide range of crucial biological activities in nature. We report here a novel expansion of these studies by introducing gluco- or galactopyranosyl scaffold to the N- or 9 position (or both) of 6-Cl purine moiety via Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. By such an efficient reaction, a series of glycosyl-triazolyl purines were successfully synthesized in good yields. Biological evaluation showed that the majority of these glycoconjugates were good PTP1B inhibitors with IC(50) values in low micromolar range (1.5-11.1 MUM). The benzylated sugar derivatives displayed better inhibitory potency than that of the acetylated ones. Replacement of Cl by MeO at C(6) of the purine moiety decreased the inhibition in the case of benzylated (glycosyl-mono-triazolyl)-purines 11 and 12 (IC(50) >80 MUM), whereas MeO-substituted benzylated bis[galactosyl-triazolyl]-purine 16 possessed the best inhibitory activity with an IC(50) value of 1.5 MUM. Additionally, these compounds exhibited 2- to 57-fold selectivity over other PTPs (TCPTP, SHP1, SHP2, and LAR). PMID- 22083917 TI - Sea sand disruption method (SSDM) as a valuable tool for isolating essential oil components from conifers. AB - Essential oils are one of nature's most precious gifts with surprisingly potent and outstanding properties. Coniferous oils, for instance, are nowadays being used extensively to treat or prevent many types of infections, modify immune responses, soothe inflammations, stabilize moods, and to help ease all forms of non-acute pain. Given the broad spectrum of usage of coniferous essential oils, a fast, safe, simple, and efficient sample-preparation method is needed in the estimation procedure of essential oil components in fresh plant material. Generally, the time- and energy-consuming steam distillation (SD) is applied for this purpose. This paper will compare SD, pressurized liquid extraction (PLE), matrix solid-phase dispersion (MSPD), and the sea sand disruption method (SSDM) as isolation techniques to obtain aroma components from Scots pine (Pinus sylvestris), spruce (Picea abies), and Douglas fir (Pseudotsuga menziesii). According to the obtained data, SSDM is the most efficient sample preparation method in determining the essential oil composition of conifers. Moreover, SSDM requires small organic solvent amounts and a short extraction time, which makes it an advantageous alternative procedure for the routine analysis of coniferous oils. The superiority of SSDM over MSPD efficiency is ascertained, as there are no chemical interactions between the plant cell components and the sand. This fact confirms the reliability and efficacy of SSDM for the analysis of volatile oil components. PMID- 22083918 TI - Volatile components of whole and different plant parts of bastard balm (Melittis melissophyllum L., Lamiaceae) collected in Central Italy and Slovakia. AB - The aim of this work was to trap the volatiles released from whole frozen and dry aerial parts, and, separately, from different organs (leaves, stems, corolla and calyx) of bastard balm (Melittis melissophyllum L., Lamiaceae) populations collected in Italy and Slovakia by HS-SPME, and to identify the headspace constituents responsible for the characteristic aroma impression by GC/FID and GC/MS techniques. Among more than 100 volatile components detected, the C(8) alcohol oct-1-en-3-ol, responsible for the typical mushroom-like odor, and the phenolic coumarin, with a characteristic sweet and creamy vanilla bean odor, played a major role in the aroma of whole aerial parts and different plant organ samples. In particular, dry calyx parts could be proposed as flavoring agent in food products as mushroom aroma enhancer. Multivariate chemometric techniques, such as cluster analysis and principal component analysis, were used to characterize the sample populations according to the geographical origin and processing of plant material. PMID- 22083919 TI - Secondary metabolites from two species of Pulicaria and their cytotoxic activity. AB - Two new compounds, the sesquiterpene (1E,5E)-8beta-acetoxy-4alpha-hydroxy-7betaH germacra-1(10),5-dien-14-oic acid (2), and a nor-sesquiterpene, (5E)-8beta acetoxy-4alpha-hydroxy-7betaH-germacr-5-en-10-one (3), were isolated from Pulicaria canariensis ssp. lanata, along with ten known compounds, including the flavonoid 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (4). From Pulicaria burchardii, we isolated seven known compounds; the physical and spectroscopic data of the triterpenoid 3beta-hydroxytaraxaster-20-en-30-al (1) are reported. The structures of compounds 1-3 were determined on the basis of HR-MS, and 1D- and 2D-NMR studies. The structure of 2 was corroborated by X-ray crystal diffraction. Cell viability experiments revealed that the semisynthetic flavonoid 4b was the most cytotoxic compound against human leukemia cells, and the cytotoxicity was caused by induction of apoptosis, as determined by microscopy of nuclear changes. PMID- 22083920 TI - Glucosinolate distribution in aerial parts of Degenia velebitica. AB - The glucosinolates present in the leaf, stem, and seed extracts of Degenia velebitica (Degen) Hayek were characterized and quantified according to the ISO 9167-1 method, which is based on the HPLC analysis of desulfoglucosinolates. The stems contained glucoalyssin (3a) as the major compound as well as glucoberteroin (1a) and glucoaubrietin (4a). The leaves contained three glucosinolates, the major one being 3a, followed by glucobrassicanapin (2a) and 1a. Glucoberteroin (1a) was the major glucosinolate in the seeds, along with the two minor glucosinolates 3a and glucoerucin (5a). The content of 1a in the whole, non defatted seeds amounted to 4% (w/w). The compound was characterized as its desulfo counterpart by spectroscopic techniques. PMID- 22083922 TI - Honatisine, a novel diterpenoid alkaloid, and six known alkaloids from Delphinium honanense and their cytotoxic activity. AB - A novel diterpene alkaloid named honatisine (1) has been isolated from the whole plants of Delphinium honanense, along with six known alkaloids, siwanine E (2), isoatisine (3), atisine (4), delcorinine (5), uraphine (6), and nordhagenine A (7). Their structures were deduced on the basis of their spectral data. All of them were evaluated by a SRB assay for their cytotoxicity, and compound 1 showed a significant cytotoxic activity (IC(50) =3.16 MUM) against the MCF-7 cell line. PMID- 22083921 TI - Armenin and isoarmenin--two prenylated coumarins from the aerial parts of Artemisia armeniaca. AB - The reversed-phase (RP) preparative HPLC analyses of the MeOH extract of the aerial parts of Artemisia armeniaca yielded four prenylated coumarins, 7-hydroxy 8-(4-hydroxy-3-methylbutoxy)coumarin (named armenin), 8-hydroxy-7-(4-hydroxy-3 methylbutoxy)coumarin (named isoarmenin), lacarol, and deoxylacarol, together with five other compounds, including three flavonoid glycosides, quercetin 3-O beta-D-glucopyranoside, rutin, and kaempferol 3-O-beta-D-glucopyranoside, and chlorogenic acid, and tryptophan. (10E,12Z)-9-Hydroxyoctadeca-10,12-dienoic acid (beta-dimorphecolic acid) was isolated from the CH(2)Cl(2) extract. Armenin and isoarmenin were new coumarins. Structures of all compounds were determined by spectroscopic means, including UV, MS, 1D- and 2D-NMR. The in vitro free-radical scavenging property of the extracts and isolated compounds was evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. PMID- 22083923 TI - Phenolic compounds from the rhizomes of Dioscorea bulbifera. AB - One new bibenzyl, 7, and one new diarylheptanone, diobulbinone A (18), together with sixteen known compounds, 1-6 and 8-17, have been isolated form the rhizomes of Dioscorea bulbifera. Their structures were elucidated by NMR and MS analyses. Compound 7 showed high antioxidant capacity in FRAP assay and DPPH radical scavenging activity. PMID- 22083924 TI - Four new doramectin congeners with acaricidal and insecticidal activity from Streptomyces avermitilis NEAU1069. AB - Four new doramectin congeners, 1-4, were isolated from Streptomyces avermitilis NEAU1069. The structures of 1-4 were elucidated on the basis of spectroscopic analysis, including 1D- and 2D-NMR as well as HR-ESI-MS, ESI-MS, UV, and IR, and comparison with literature data. All compounds exhibited noticeable acaricidal and insecticidal activities. Especially compound 2 was found to be the most potent pesticide of the compounds evaluated with the IC(50) values of 10.2, 65.1 and 124.4 MUg/ml against adult two-spotted spider mites (Tetranychus urticae Koch), two-spotted spider mite eggs, and Mythimna separata, respectively, which are comparable to those of commercial pesticide milbemycin A(3)/A(4) as positive reference. PMID- 22083925 TI - Phenolic derivatives from Ruprechtia polystachya and their inhibitory activities on the glucose-6-phosphatase system. AB - Two new compounds, 5-methyl-2-(2-methylbutanoyl)phloroglucinol 1-O-(6-O-beta-D apiofuranosyl)-beta-D-glucopyranoside (1) and trans-2,3-dihydrokaempferol 3-O-(4 O-sulfo)-alpha-L-arabinopyranoside (2), together with 14 known flavonoids, trans dihydrokaempferol 3-O-alpha-L-arabinopyranoside (3), trans-taxifolin 3-O-alpha-L arabinofuranoside (4), quercetin 3-O-alpha-L-rhamnopyranoside (5), quercetin 3'-O alpha-L-arabinofuranoside (6), catechin 3-O-alpha-L-rhamnopyranoside (7), trans taxifolin 3-O-alpha-L-arabinopyranoside (8), cis-dihydrokaempferol 3-O-alpha-L arabinopyranoside (9), catechin (10), myricetin 3-O-alpha-L-rhamnopyranoside (11), quercetin 3-O-alpha-L-arabinopyranoside (12), quercetin 3-O-alpha-L arabinofuranoside (13), quercetin 3-O-(3"-galloyl)-alpha-L-rhamnopyranoside (14), quercetin 3-O-(2"-galloyl)-alpha-L-rhamnopyranoside (15), and epicatechin 3-O gallate (16), were isolated from the leaves of Ruprechtia polystachya Griseb. (Polygonaceae). Their structures were established on the basis of extensive 1D- and 2D-NMR experiments as well as MS analyses. All compounds, except 1, showed inhibition of the enzyme glucose-6-phosphatase in intact microsomes. PMID- 22083926 TI - Triterpenes from the fungus Poria cocos and their inhibitory activity on nitric oxide production in mouse macrophages via blockade of activating protein-1 pathway. AB - Two new triterpenes, 29-hydroxydehydrotumulosic acid (1) and 29 hydroxydehydropachymic acid (2), together with six known compounds, dehydropachymic acid (3), dehydrotumulosic acid (4), 29-hydroxypolyporenic acid C (5), polyporenic acid C (6), tumulosic acid (7), and pachymic acid (8), were isolated from the dried sclerotia of Poria cocos. In the in vitro bioassays, these isolated compounds reduced, in a dose-dependent manner, nitric oxide (NO) production from lipopolysaccharide (LPS)-induced RAW 264.7 cells, with compounds 5 and 6, the IC(50) values of which were 16.8+/-2.7 and 18.2+/-3.3 MUM, respectively, exhibiting the greatest inhibition activity. Further Western blot analysis conducted on cells pre-treated with compounds 5 and 6, and luciferase assays on activator protein 1-dependent gene expression revealed that the inhibited NO release was attributed to the reduced expression of iNOs (=inducible NO synthase) enzymes, which might be regulated via the blockade of activator protein-1 signaling pathway. PMID- 22083927 TI - Anticandidal activity of the essential oil of Nepeta transcaucasica Grossh. AB - Hydrodistallation of the aerial parts of Nepeta transcaucasica Grossh. (Lamiaceae), collected in Agri, Dogubayazit Province, afforded an essential oil that was characterized by GC and GC/MS analyses. Twenty-seven compounds, representing 97.69% of the total oil composition, were identified, and 4aalpha,7alpha,7abeta-nepetalactone (1; 39%), 4aalpha,7alpha,7aalpha nepetalactone (2; 28%), and germacrene D (3; 15%) constituted the major components. The anticandidal effects of the oil were evaluated against seven Candida strains by using the broth microdilution method. The oil showed good inhibitory effects against C. glabrata and C. tropicalis at minimal inhibitory concentrations (MICs) of 0.09 and 0.375 mg/ml, respectively. PMID- 22083928 TI - Chemical composition and in vitro schistosomicidal activity of the essential oil of Plectranthus neochilus grown in Southeast Brazil. AB - The chemical composition and the in vitro schistosomicidal effects of the essential oil of Plectranthus neochilus (PN-EO) grown in Southeast Brazil was studied. beta-Caryophyllene (1; 28.23%), alpha-thujene (2; 12.22%), alpha-pinene (3; 12.63%), beta-pinene (4; 6.19%), germacrene D (5; 5.36%), and caryophyllene oxide (6; 5.37%) were the major essential oil constituents. This chemical composition differed from that previously reported for specimens harvested in Africa. Concerning the in vitro schistosomicidal activity against adult Schistosoma mansoni worms, PN-EO was considered to be active, but less effective than the positive control praziquantel (PZQ) in terms of separation of coupled pairs, mortality, decrease in the motor activity, and tegumental alterations. However, PN-EO caused an interesting dose-dependent reduction in the number and the percentage of developed S. mansoni eggs. These results suggest that PN-EO might be very promising for the development of new schistosomicidal agents. PMID- 22083929 TI - Chemistry students and human rights. PMID- 22083930 TI - Effect of feed intake level on ileal digestibilities of crude protein and amino acids in diets for piglets. AB - BACKGROUND: The study was conducted to determine the effect of graded levels of feed intake on apparent (AID) and standardized (SID) ileal digestibilities of crude protein (CP) and amino acids (AA) in diets for piglets. The piglets were surgically fitted with simple T-cannulas at the distal ileum. The cornstarch casein-soybean meal-based diets were fed at three graded levels of feed intake corresponding to 30, 45 and 60 g kg(-1) body weight (BW) per day. RESULTS: The AID and SID of most AA were quadratically affected by the feed intake level (P<=0.05). Initially, both AID and SID of most AA increased up to 1.9 percentage units as the feed intake level was increased from 30 to 45 g kg(-1) BW. Thereafter, these AID and SID values decreased by 2.6 and 2.7 percentage units, respectively, as the feed intake level was further increased from 45 to 60 g kg( 1) BW. CONCLUSION: Because the voluntary feed intake is highly variable in piglets after weaning, comparison of ileal AA digestibilities between and within studies may be confounded by variations in feed intake level. Thus, when designing digestibility studies with piglets, a standardization of feed intake should be taken into consideration. PMID- 22083931 TI - Recruitment and enrollment of caregivers for a lifestyle physical activity clinical trial. AB - This article presents the efficacy of the recruitment framework used for a clinical trial with sedentary family caregivers of persons with Alzheimer's disease. An integrated social marketing approach with principles of community based participatory research provided the theoretical framework for organizing recruitment activities. This multi-pronged approach meant that caregivers were identified from a range of geographic locations and numerous sources including a federally funded Alzheimer's disease center, health care providers, community based and senior organizations, and broad-based media. Study enrollment projections were exceeded by 11% and resulted in enrolling n = 211 caregivers into this clinical trial. We conclude that social marketing and community-based approaches provide a solid foundation for organizing recruitment activities for clinical trials with older adults. PMID- 22083932 TI - Predicting pulmonary adenocarcinoma outcome based on a cytology grading system. AB - BACKGROUND: Pulmonary adenocarcinoma (AD) has a variety of architectural patterns. Recently, a 3-tiered histological pattern-based grading system was developed for stage I lung AD, stratifying patients into low, intermediate, and high risk for recurrence. However, cytology may serve as the primary method for diagnosis in patients with inoperable disease. Attempts to correlate architecture between parallel cytological and histological preparations have not been successful. Therefore, we evaluated cytomorphologic features of previously histologically graded AD to identify features of potential prognostic significance. METHODS: One hundred and thirteen fine-needle aspirations with excised adenocarcinomas were reviewed. In the liquid-based preparation, we evaluated cell arrangements(flat sheets vs 3-D clusters vs single cells), nuclear features (size variability, shape, and contour),nucleoli (prominent or inconspicuous), presence of nuclear inclusions, chromatin (fine, coarse,or clumped), and quality of background. The features were tested by multivariate analysis to identify associations with histological grade and disease-free survival (DFS), and a cytological score was generated. RESULTS: Nuclear size, chromatin pattern, and nuclear contours showed a significant association with histological grade and DFS. These features were included in the composite cytological score (range,0-5). By grouping the cytological scores, we stratified the tumors into low (median DFS, 100%), intermediate(median DFS, 78%), and high (median DFS, 55%) rate of recurrence (P 1/4 .008). There was a good correlation with the histological grading system. CONCLUSIONS: In liquid-based preparations, distinctive cytological features of pulmonary adenocarcinoma correlate with levels of histological differentiation and can be combined into a score with prognostic significance. PMID- 22083933 TI - Effect of diet on the incidence of and mortality owing to gastritis and renal disease in captive cheetahs (Acinonyx jubatus) in South Africa. AB - Seventy-two adult cheetahs were evaluated for the degree of gastritis by endoscopic biopsy and for renal disease by serum creatinine. Cheetahs free of Grade 3 gastritis and renal disease were placed on Trial A; remaining cheetahs were placed on Trial B, which ran concurrently. All cheetahs were monitored for 4 years. Cheetahs exited Trial A and entered Trial B if they developed Grade 3 gastritis or renal disease. Cheetahs exited Trial B if they developed clinical gastritis or renal disease that required a dietary change or aggressive medical therapy or died owing to either disease. Cheetahs on Trial A were fed either a supplemented meat diet (N = 26) or commercial cat food (N = 22). Cheetahs on Trial B were fed either the same meat diet (N = 28) or a commercial dry cat food formulated for renal disease (N = 16). Cheetahs fed meat on Trial A had a daily hazard of developing Grade 3 gastritis 2.21 times higher (95% CI 0.95-5.15) than cheetahs fed commercial cat food. This hazard was not statistically significant (P = 0.07). Mean gastritis scores were not significantly different between the two groups. Cheetahs fed commercial cat food in both Trials had lower serum urea levels and higher creatinine levels than those fed meat. Evidence for the effect of diet in cheetahs with gastritis and/or renal disease (Trial B) was inconclusive. The number of cheetahs dying of gastritis or renal disease at the facility has dropped markedly since the study began. These results indicate that diet may play an important role in the incidence of Grade 3 gastritis and that dietary and/or therapeutic management of gastritis may reduce mortality owing to gastritis and renal disease in captive cheetahs. PMID- 22083934 TI - Location, location, cis-mutation. PMID- 22083935 TI - BAG3 in heart disease: novel clues for cardiomyocyte survival from the Z-disk? PMID- 22083936 TI - High-performance organic optoelectronic devices enhanced by surface plasmon resonance. AB - The surface plasmon effect on polymer solar cells and polymer light-emitting diodes is demonstrated by using metal nanoparticles prepared from block copolymer templates. Light absorption of the polymer thin layer is increased with the incorporation of metallic nanostructures, resulting in a significant surface plasmon effect in the optoelectronic devices. PMID- 22083937 TI - Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma. AB - BACKGROUND: Tumor markers are genes or their products expressed exclusively or preferentially in tumor cells and cancer-testis antigens (CTAs) form a group of genes with a typical expression pattern expressed in a variety of malignant neoplasms. CTAs are considered potential targets for cancer vaccines. It is possible that the CTA MAGE-A4 (melanoma antigen) and MAGE-C1 are expressed in carcinoma of the oral cavity and are related with survival. METHODS: This study involved immunohistochemical analysis of 23 patients with oral squamous cell carcinoma (SCC) and was carried out using antibodies for MAGE-A4 and MAGE-C1. Fisher's exact test and log-rank test were used to evaluate the results. RESULTS: The expression of the MAGE-A4 and MAGE-C1 were 56.5% and 47.8% without statistical difference in studied variables and survival. CONCLUSION: The expression of at least 1 CTA was present in 78.3% of the patients, however, without correlation with clinicopathologic variables and survival. PMID- 22083938 TI - Quinone-based, redox-active resorcin[4]arene cavitands. PMID- 22083939 TI - Squaraine dyes as efficient coupling bridges between triarylamine redox centres. AB - Various indolenine squarylium dyes with additional electron-donating amine redox centres have been synthesised and their redox chemistry has been studied. A combination of cyclic voltammetry, spectro-electrochemistry and DFT calculations has been used to characterise the electronic structure of the mono-, di- and, in one case, trications. All monocations still retain the cyanine-like, delocalised character due to the relatively low redox potential of the squaraine bridge and are therefore compounds of Robin-Day class III. Thus we extended previous studies on organic mixed-valence systems by using the indolenine squaraine moiety as very electron-rich bridge between two electron-donating amine redox centres to provoke a strong coupling between the additional redox centres. We synthesised TA3, which has an N-N distance of 26 bonds between the triarylamine redox centres and is to our knowledge the longest bis(triarylamine) radical cation that is completely delocalised. We furthermore show that altering the symmetry of a squaraine dye by substitution of a squaric ring oxygen atom by a dicyanomethylene group has a direct impact on the optical properties of the monocations. In case of the dications, it turned out that the energetically most stable state of dianisylamine-substituted squaraines is an anti-ferromagnetically coupled open shell singlet state. PMID- 22083940 TI - Risk factors of cardiac troponin T elevation in patients with stable coronary artery disease after elective coronary drug-eluting stent implantation. AB - BACKGROUND: Cardiac troponin T elevation after coronary intervention has been demonstrated to be associated with the prognosis of coronary artery disease (CAD). However, there were few studies about comprehensive risk factors analysis of troponin T elevation after elective drug-eluting stent (DES) implantation. HYPOTHESIS: The prognosis of CAD after coronary interventions was associated with clinical and procedural risk factors of CAD, such as age, hypertension, severity extent of CAD and so on. METHODS: From March to December in 2010, patients with stable CAD were admitted for elective coronary intervention in our hospital. They were divided into an elevated troponin T group and a normal troponin T group by postprocedural troponin T. Clinical factors, laboratory-test factors, and angiographic factors (such as gender, age, cholesterol, Gensini score, and others) were analyzed. RESULTS: A total of 209 patients with an average age of 64.0 +/- 9.9 years were enrolled in the study: 70 patients with elevated troponin T (>=0.03 ng/mL) after DES implantation and 139 patients with normal troponin T (<0.03 ng/mL). After univariate analysis, we found that age, hypertension, total cholesterol, low density lipoprotein-cholesterol (LDL-C), Gensini score, number of stenosed vessels, and total implanted stents were associated with postprocedural troponin T elevation. According to the results of multivariate analysis, we found that age, total cholesterol, number of stenosed vessels, and number of implanted stents were independent risk factors of postprocedural troponin T elevation. CONCLUSIONS: Age, serum total cholesterol, number of stenosed vessels, and number of implanted stents could be independent risk factors of troponin T elevation after elective DES implantation. PMID- 22083941 TI - Molecular mechanisms for anti-aging by natural dietary compounds. AB - Aging is defined as a normal decline in survival with advancing age; however, the recent researches have showed that physiological functions of the body change during the aging process. Majority of the changes are often subject to a higher risk of developing diseases, such as cardiovascular disease, type II diabetes, Alzheimer's disease, Parkinson's disease, as well as the dysregulated immune and inflammatory disorders. Aging process is controlled by a complicated and precise signaling network that involved in energy homeostasis, cellular metabolism and stress resistance. Over the past few decades, research in natural dietary compounds by various organism and animal models provides a new strategy for anti aging. Natural dietary compounds act through a variety mechanisms to extend lifespan and prevent age-related diseases. This review summarizes the current understanding on signaling pathways of aging and knowledge and underlying mechanism of natural dietary compounds that provide potential application on anti aging and improve heath in human. PMID- 22083942 TI - Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration. AB - The notochordal cell (NC) of the nucleus pulposus (NP) is considered a potential NP progenitor cell, and early intervertebral disk (IVD) degeneration involves replacement of NCs by chondrocyte-like cells (CLCs). Wnt/beta-catenin signaling plays a crucial role in maintaining the notochordal fate during embryogenesis, but is also involved in tissue degeneration and regeneration. The canine species, which can be subdivided into non-chondrodystrophic and chondrodystrophic breeds, is characterized by differential maintenance of the NC: in non-chondrodystrophic dogs, the NC remains the predominant cell type during the majority of life, with IVD degeneration only occurring at old age; conversely, in chondrodystrophic dogs the NC is lost early in life, with concurrent degeneration of all IVDs. This study investigated Wnt/beta-catenin signaling in the healthy, NC-rich NP and early degenerated, CLC-rich NP of both breed types by immunohistochemistry of beta-catenin and relative gene expression of brachyury and cytokeratin 8 (notochordal markers) and Wnt targets axin2, cyclin D1, and c-myc. Both NCs and CLCs showed nuclear and cytoplasmic beta-catenin protein expression and axin2 gene expression, but beta-catenin signal intensity and Wnt target gene expression were higher in the CLC-rich NP. Primary NCs in monolayer culture (normoxic conditions) showed Wnt/beta-catenin signaling comparable to the in vivo situation, with increased cyclin D1 and c-myc gene expression. In conclusion, Wnt/beta-catenin signaling activity in the NC within the NC-rich NP and in culture supports the role of this cell as a potential progenitor cell; increased Wnt/beta-catenin signaling activity in early IVD degeneration may be a reflection of its dual role. PMID- 22083943 TI - Nanoscale DNA tetrahedra improve biomolecular recognition on patterned surfaces. AB - The bottom-up approach of DNA nano-biotechnology can create biomaterials with defined properties relevant for a wide range of applications. This report describes nanoscale DNA tetrahedra that are beneficial to the field of biosensing and the targeted immobilization of biochemical receptors on substrate surfaces. The DNA nanostructures act as immobilization agents that are able to present individual molecules at a defined nanoscale distance to the solvent thereby improving biomolecular recognition of analytes. The tetrahedral display devices are self-assembled from four oligonucleotides. Three of the four tetrahedron vertices are equipped with disulfide groups to enable oriented binding to gold surfaces. The fourth vertex at the top of the bound tetrahedron presents the biomolecular receptor to the solvent. In assays testing the molecular accessibility via DNA hybridization and protein capturing, tetrahedron-tethered receptors outperformed conventional immobilization approaches with regard to specificity and amount of captured polypeptide by a factor of up to seven. The bottom-up strategy of creating DNA tetrahedrons is also compatible with the top down route of nanopatterning of inorganic substrates, as demonstrated by the specific coating of micro- to nanoscale gold squares amid surrounding blank or poly(ethylene glycol)-passivated glass surfaces. DNA tetrahedra can create biofunctionalized surfaces of rationally designed properties that are of relevance in analytical chemistry, cell biology, and single-molecule biophysics. PMID- 22083944 TI - Differential effect of beta-blockers for heart rate control in coronary artery disease. AB - BACKGROUND: Resting heart rate is an independent risk factor for cardiovascular disease and is mainly controlled by beta-blockers (BBs). BBs are part of the optimal medical treatment for coronary artery disease (CAD), and their benefit correlates with resting heart rate (RHR) reduction. HYPOTHESIS: RHR is poorly controlled in daily practice among patients with stable cardiovascular disease, and control is only achieved by some BBs. METHODS: Observational, cross sectional, and multicenter study of CAD patients recruited nationwide from 20 institutions. Antecedents, risk factors, and treatments were collected. Controlled RHR was considered at <70 bpm. RESULTS: The mean age of the 2897 patients included was 67.4 years (11.4%), and 75.9% were males. Patients treated with a BB (56.5%) had a lower mean age and comorbidities. The mean RHR was 69.6 bpm (12.6). A significantly lower RHR was observed in patients treated with a BB compared to the rest (67.2 vs 73.0 bpm; P<0.01), and no difference was observed in patients treated with a calciumchannel blocker (CCB). The analysis by individual agents identified that only patients treated with atenolol, bisoprolol, and metoprolol had significantly lower RHR than those not receiving a BB. No differences were observed in mean doses of each agent according to RHR control, except for verapamil. BB treatment was independently associated with RHR control (odds ratio [OR]: 2.42, 95% CI: 2.05-2.87; P<0.01), and no association was found for nondihydropyridine CCBs (OR: 0.99, 95% CI: 0.96-1.02; P = 0.38). Bisoprolol (OR: 1.56, 95% CI: 1.38-1.78; P<0.01), atenolol (OR: 2.01, 95% CI: 1.57-3.49; P<0.01), and metoprolol (OR: 1.29, 95% CI: 1.04-1618; P = 0.04) were independently associated with RHR control. CONCLUSIONS: RHR is poorly controlled in CAD patients, and although BBs are the most efficient therapy, in daily clinical practice RHR <70 bpm is only independently associated with atenolol, bisoprolol, or metoprolol. PMID- 22083945 TI - Mapping hemodynamic correlates of seizures using fMRI: A review. AB - Functional magnetic resonance imaging (fMRI) is able to detect changes in blood oxygenation level associated with neuronal activity throughout the brain. For more than a decade, fMRI alone or in combination with simultaneous EEG recording (EEG-fMRI) has been used to investigate the hemodynamic changes associated with interictal and ictal epileptic discharges. This is the first literature review to focus on the various fMRI acquisition and data analysis methods applied to map epileptic seizure-related hemodynamic changes from the first report of an fMRI scan of a seizure to the present day. Two types of data analysis approaches, based on temporal correlation and data driven, are explained and contrasted. The spatial and temporal relationship between the observed hemodynamic changes using fMRI and other non-invasive and invasive electrophysiological and imaging data is considered. We then describe the role of fMRI in localizing and exploring the networks involved in spontaneous and triggered seizure onset and propagation. We also discuss that fMRI alone and combined with EEG hold great promise in the investigation of seizure-related hemodynamic changes non-invasively in humans. We think that this will lead to significant improvements in our understanding of seizures with important consequences for the treatment of epilepsy. PMID- 22083948 TI - Cross-coupling of aryl Grignard reagents with aryl iodides and bromides through S(RN)1 pathway. PMID- 22083949 TI - Plasma Epstein-Barr virus DNA concentration and clearance rate as novel prognostic factors for metastatic nasopharyngeal carcinoma. AB - BACKGROUND: To investigate the pretreatment copy number and the clearance rate of plasma Epstein-Barr virus (EBV) DNA as novel prognostic outcome markers for metastatic nasopharyngeal carcinoma (NPC). METHODS: Seventy-three patients with metastatic NPC were treated at outpatient department. Plasma EBV DNA concentrations and half-life values of plasma viral clearance rates, were determined by real-time quantitative polymerase chain reaction. RESULTS: Treatment response evaluated after 3 to 6 months of treatment showed that the overall response rate was 53.5%. The pretreatment plasma EBV DNA concentrations and the half-life of plasma EBV DNA clearance rates had significant effects on treatment response and overall survival prediction. In the chemotherapy regimen, gemcitabine plus cisplatin had a better treatment outcome than the cisplatin plus oral UFT and calcium folinate-based regimens. CONCLUSIONS: The pretreatment plasma EBV DNA copy number and their clearance rates are significant predictors for NPC treatment outcome. PMID- 22083951 TI - New insights into cyclobutenone rearrangements: a total synthesis of the natural ROS-generating anti-cancer agent cribrostatin 6. AB - Aryl- and heteroarylcyclobutenone rearrangements proceed in excellent yield under continuous-flow conditions. The former shows a Hammett correlation with sigma(I) providing strong evidence that electrocyclisation is the rate-determining step and has a late transition state. The reaction has been modelled by using DFT and CCSD(T) methods, with the latter giving excellent correlation with the experimental rate constant. A short and efficient total synthesis of cribrostatin 6, an anti-neoplastic and anti-microbial agent, provides a topical demonstration of the value of this method. PMID- 22083950 TI - Regulation of epithelial permeability by the actin cytoskeleton. AB - The actin cytoskeleton is a dynamic structure necessary for cell and tissue organization, including the maintenance of epithelial barriers. The epithelial barrier regulates the movement of ions, macromolecules, immune cells, and pathogens, and is thus essential for normal organ function. Disruption in the epithelial barrier has been shown to coincide with alterations of the actin cytoskeleton in several disease states. These disruptions primarily manifest as increased movement through the paracellular space, which is normally regulated by tight junctions (TJ). Despite extensive research demonstrating a direct link between the actin cytoskeleton and epithelial permeability, our understanding of the physiological mechanisms that link permeability and tight junction structure are still limited. In this review, we explore the role of the actin cytoskeleton at TJ and present several areas for future study. PMID- 22083952 TI - The forkhead transcription factor FOXK2 promotes AP-1-mediated transcriptional regulation. AB - The transcriptional control circuitry in eukaryotic cells is complex and is orchestrated by combinatorially acting transcription factors. Forkhead transcription factors often function in concert with heterotypic transcription factors to specify distinct transcriptional programs. Here, we demonstrate that FOXK2 participates in combinatorial transcriptional control with the AP-1 transcription factor. FOXK2 binding regions are widespread throughout the genome and are often coassociated with AP-1 binding motifs. FOXK2 acts to promote AP-1 dependent gene expression changes in response to activation of the AP-1 pathway. In this context, FOXK2 is required for the efficient recruitment of AP-1 to chromatin. Thus, we have uncovered an important new molecular mechanism that controls AP-1-dependent gene expression. PMID- 22083953 TI - RBFOX2 promotes protein 4.1R exon 16 selection via U1 snRNP recruitment. AB - The erythroid differentiation-specific splicing switch of protein 4.1R exon 16, which encodes a spectrin/actin-binding peptide critical for erythrocyte membrane stability, is modulated by the differentiation-induced splicing factor RBFOX2. We have now characterized the mechanism by which RBFOX2 regulates exon 16 splicing through the downstream intronic element UGCAUG. Exon 16 possesses a weak 5' splice site (GAG/GTTTGT), which when strengthened to a consensus sequence (GAG/GTAAGT) leads to near-total exon 16 inclusion. Impaired RBFOX2 binding reduces exon 16 inclusion in the context of the native weak 5' splice site, but not the engineered strong 5' splice site, implying that RBFOX2 achieves its effect by promoting utilization of the weak 5' splice site. We further demonstrate that RBFOX2 increases U1 snRNP recruitment to the weak 5' splice site through direct interaction between its C-terminal domain (CTD) and the zinc finger region of U1C and that the CTD is required for the effect of RBFOX2 on exon 16 splicing. Our data suggest a novel mechanism for exon 16 5' splice site activation in which the binding of RBFOX2 to downstream intronic splicing enhancers stabilizes the pre-mRNA-U1 snRNP complex through interactions with U1C. PMID- 22083954 TI - Novel roles of Caenorhabditis elegans heterochromatin protein HP1 and linker histone in the regulation of innate immune gene expression. AB - Linker histone (H1) and heterochromatin protein 1 (HP1) are essential components of heterochromatin which contribute to the transcriptional repression of genes. It has been shown that the methylation mark of vertebrate histone H1 is specifically recognized by the chromodomain of HP1. However, the exact biological role of linker histone binding to HP1 has not been determined. Here, we investigate the function of the Caenorhabditis elegans H1 variant HIS-24 and the HP1-like proteins HPL-1 and HPL-2 in the cooperative transcriptional regulation of immune-relevant genes. We provide the first evidence that HPL-1 interacts with HIS-24 monomethylated at lysine 14 (HIS-24K14me1) and associates in vivo with promoters of genes involved in antimicrobial response. We also report an increase in overall cellular levels and alterations in the distribution of HIS-24K14me1 after infection with pathogenic bacteria. HIS-24K14me1 localization changes from being mostly nuclear to both nuclear and cytoplasmic in the intestinal cells of infected animals. Our results highlight an antimicrobial role of HIS-24K14me1 and suggest a functional link between epigenetic regulation by an HP1/H1 complex and the innate immune system in C. elegans. PMID- 22083955 TI - Occludin: one protein, many forms. AB - Intercellular tight junctions (TJs) exhibit a complex molecular architecture involving the regulated cointeraction of cytoplasmic adaptor proteins (e.g., zonula occludens) and integral membrane linker proteins (e.g., occludin and claudins). They provide structural integrity to epithelial and endothelial tissues and create highly polarized barriers essential to homeostatic maintenance within vertebrate physiological systems, while their dysregulation is an established pathophysiological hallmark of many diseases (e.g., cancer, stroke, and inflammatory lung disease). The junctional complex itself is a highly dynamic signaling entity wherein participant proteins constantly undergo a blend of regulatory modifications in response to diverse physiological and pathological cues, ultimately diversifying the overall adhesive properties of the TJ. Occludin, a 65-kDa tetraspan integral membrane protein, contributes to TJ stabilization and optimal barrier function. This paper reviews our current knowledge of how tissue occludin is specifically modified at the posttranscriptional and posttranslational levels in diverse circumstances, with associated consequences for TJ dynamics and epithelial/endothelial homeostasis. Mechanistic concepts such as splice variance and alternate promoter usage, proteolysis, phosphorylation, dimerization, and ubiquitination are comprehensively examined, and possible avenues for future investigation highlighted. PMID- 22083956 TI - CBP mediates NF-kappaB-dependent histone acetylation and estrogen receptor recruitment to an estrogen response element in the BIRC3 promoter. AB - Estrogen receptor (ER) and NF-kappaB are transcription factors with profound effects on breast cancer cell proliferation and survival. While many studies demonstrate that ER and NF-kappaB can repress each other, we previously identified a gene signature that is synergistically upregulated by these two factors in more aggressive luminal B breast tumors. Herein, we examine a novel mechanism of cross talk between ER and NF-kappaB that results in the upregulation of the antiapoptotic gene BIRC3 (also known as cIAP2). We demonstrate that NF kappaB, acting through two response elements, is required for ER recruitment to an adjacent estrogen response element (ERE) in the BIRC3 promoter. This effect is accompanied by a major increase in NF-kappaB-dependent histone acetylation around the ERE. Interestingly, CBP, a histone acetyltransferase previously implicated in repressive interactions between ER and NF-kappaB, plays a permissive role by promoting histone acetylation and ER recruitment, as well as enhanced expression of BIRC3. These findings suggest a new gene regulatory mechanism by which inflammation and NF-kappaB activation can influence ER recruitment to inherently inactive ER binding sites. This fine-tuning mechanism may explain how two factors that generally repress each other's activity may work together on certain genes to promote breast cancer cell survival and tumor progression. PMID- 22083957 TI - Integration of regulatory networks by NKX3-1 promotes androgen-dependent prostate cancer survival. AB - The NKX3-1 gene is a homeobox gene required for prostate tumor progression, but how it functions is unclear. Here, using chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) we showed that NKX3-1 colocalizes with the androgen receptor (AR) across the prostate cancer genome. We uncovered two distinct mechanisms by which NKX3-1 controls the AR transcriptional network in prostate cancer. First, NKX3-1 and AR directly regulate each other in a feed forward regulatory loop. Second, NKX3-1 collaborates with AR and FoxA1 to mediate genes in advanced and recurrent prostate carcinoma. NKX3-1- and AR-coregulated genes include those found in the "protein trafficking" process, which integrates oncogenic signaling pathways. Moreover, we demonstrate that NKX3-1, AR, and FoxA1 promote prostate cancer cell survival by directly upregulating RAB3B, a member of the RAB GTPase family. Finally, we show that RAB3B is overexpressed in prostate cancer patients, suggesting that RAB3B together with AR, FoxA1, and NKX3-1 are important regulators of prostate cancer progression. Collectively, our work highlights a novel hierarchical transcriptional regulatory network between NKX3 1, AR, and the RAB GTPase signaling pathway that is critical for the genetic molecular-phenotypic paradigm in androgen-dependent prostate cancer. PMID- 22083958 TI - Histone H1 recruitment by CHD8 is essential for suppression of the Wnt-beta catenin signaling pathway. AB - Members of the chromodomain helicase DNA-binding (CHD) family of proteins are thought to regulate gene expression. Among mammalian CHD proteins, CHD8 was originally isolated as a negative regulator of the Wnt-beta-catenin signaling pathway that binds directly to beta-catenin and suppresses its transactivation activity. The mechanism by which CHD8 inhibits beta-catenin-dependent transcription has been unclear, however. Here we show that CHD8 promotes the association of beta-catenin and histone H1, with formation of the trimeric complex on chromatin being required for inhibition of beta-catenin-dependent transactivation. A CHD8 mutant that lacks the histone H1 binding domain did not show such inhibitory activity, indicating that histone H1 recruitment is essential for the inhibitory effect of CHD8. Furthermore, either depletion of histone H1 or expression of a dominant negative mutant of this protein resulted in enhancement of the response to Wnt signaling. These observations reveal a new mode of regulation of the Wnt signaling pathway by CHD8, which counteracts beta catenin function through recruitment of histone H1 to Wnt target genes. Given that CHD8 is expressed predominantly during embryogenesis, it may thus contribute to setting a threshold for responsiveness to Wnt signaling that operates in a development-dependent manner. PMID- 22083959 TI - RAD6 regulates the dosage of p53 by a combination of transcriptional and posttranscriptional mechanisms. AB - Maintaining an appropriate cellular concentration of p53 is critical for cell survival and normal development in various organisms. In this study, we provide evidence that the human E2 ubiquitin-conjugating enzyme RAD6 plays a critical role in regulating p53 protein levels under both normal and stress conditions. Knockdown and overexpression of RAD6 affected p53 turnover and transcription. We showed that RAD6 can form a ternary complex with MDM2 and p53 that contributes to the degradation of p53. Chromatin immunoprecipitation (ChIP) analysis showed that RAD6 also binds to the promoter and coding regions of the p53 gene and modulates the levels of H3K4 and K79 methylation on local chromatin. When the cells were exposed to stress stimuli, the RAD6-MDM2-p53 ternary complex was disrupted; RAD6 was then recruited to the chromatin of the p53 gene, resulting in an increase in histone methylation and p53 transcription. Further studies showed that stress induced p53 transcriptional activation, cell apoptosis, and disrupted cell cycle progression are all RAD6 dependent. Overall, this work demonstrates that RAD6 regulates p53 levels in a "yin-yang" manner through a combination of two distinct mechanisms in mammalian cells. PMID- 22083960 TI - Recognition of CpG island chromatin by KDM2A requires direct and specific interaction with linker DNA. AB - Up to 70% of human genes are associated with regions of nonmethylated DNA called CpG islands (S. Saxonov, P. Berg, and D. L. Brutlag, Proc. Natl. Acad. Sci. U. S. A. 103:1412-1417, 2006). Usually associated with the 5' end of genes, CpG islands are thought to impact gene expression. We previously demonstrated that the histone demethylase KDM2A is specifically recruited to CpG islands to define a unique chromatin architecture and highlight gene regulatory regions in large and complex mammalian genomes. This targeting relies on a zinc finger CXXC DNA binding domain (ZF-CXXC), but how this demethylase interfaces with CpG island chromatin in vivo remains unknown. Here we demonstrate, using defined chromatin templates in vitro and chromatin profiling in vivo, that nucleosomes are a major barrier to KDM2A binding and that CpG islands are directly interpreted by the ZF CXXC domain through specific interaction with linker DNA. Furthermore, KDM2A appears to be constrained to CpG islands not only by their nonmethylated state but also by a combination of methylated DNA and nucleosome occlusion elsewhere in the genome. Our observations suggest that both DNA sequence and chromatin structure are defining factors in interpreting CpG island chromatin and translation of the CpG signal. More generally, these features of CpG island recognition suggest that chromatin structure and accessibility play a major role in defining how transcription factors recognize DNA and regulatory elements genome-wide. PMID- 22083961 TI - The evolutionarily conserved protein Las1 is required for pre-rRNA processing at both ends of ITS2. AB - Ribosome synthesis entails the formation of mature rRNAs from long precursor molecules, following a complex pre-rRNA processing pathway. Why the generation of mature rRNA ends is so complicated is unclear. Nor is it understood how pre-rRNA processing is coordinated at distant sites on pre-rRNA molecules. Here we characterized, in budding yeast and human cells, the evolutionarily conserved protein Las1. We found that, in both species, Las1 is required to process ITS2, which separates the 5.8S and 25S/28S rRNAs. In yeast, Las1 is required for pre rRNA processing at both ends of ITS2. It is required for Rrp6-dependent formation of the 5.8S rRNA 3' end and for Rat1-dependent formation of the 25S rRNA 5' end. We further show that the Rat1-Rai1 5'-3' exoribonuclease (exoRNase) complex functionally connects processing at both ends of the 5.8S rRNA. We suggest that pre-rRNA processing is coordinated at both ends of 5.8S rRNA and both ends of ITS2, which are brought together by pre-rRNA folding, by an RNA processing complex. Consistently, we note the conspicuous presence of ~7- or 8-nucleotide extensions on both ends of 5.8S rRNA precursors and at the 5' end of pre-25S RNAs suggestive of a protected spacer fragment of similar length. PMID- 22083962 TI - Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle. AB - Mitochondrial dysfunction in skeletal muscle has been implicated in the development of insulin resistance and type 2 diabetes. Considering the importance of mitochondrial dynamics in mitochondrial and cellular functions, we hypothesized that obesity and excess energy intake shift the balance of mitochondrial dynamics, further contributing to mitochondrial dysfunction and metabolic deterioration in skeletal muscle. First, we revealed that excess palmitate (PA), but not hyperglycemia, hyperinsulinemia, or elevated tumor necrosis factor alpha, induced mitochondrial fragmentation and increased mitochondrion-associated Drp1 and Fis1 in differentiated C2C12 muscle cells. This fragmentation was associated with increased oxidative stress, mitochondrial depolarization, loss of ATP production, and reduced insulin-stimulated glucose uptake. Both genetic and pharmacological inhibition of Drp1 attenuated PA-induced mitochondrial fragmentation, mitochondrial depolarization, and insulin resistance in C2C12 cells. Furthermore, we found smaller and shorter mitochondria and increased mitochondrial fission machinery in the skeletal muscle of mice with genetic obesity and those with diet-induced obesity. Inhibition of mitochondrial fission improved the muscle insulin signaling and systemic insulin sensitivity of obese mice. Our findings indicated that aberrant mitochondrial fission is causally associated with mitochondrial dysfunction and insulin resistance in skeletal muscle. Thus, disruption of mitochondrial dynamics may underlie the pathogenesis of muscle insulin resistance in obesity and type 2 diabetes. PMID- 22083963 TI - Visualizing human telomerase activity with primer-modified Au nanoparticles. AB - Telomerase is over-expressed in over 85% of all known human tumors. This renders the enzyme a valuable biomarker for cancer diagnosis and an important therapeutic target. The most widely used telomeric repeat amplification protocol (TRAP) assay has been questioned for telomerase detection. It is reported that human telomerase activity can be visualized by using primer-modified Au nanoparticles. The working principle is based on the elongated primers conjugated to the gold nanoparticle (AuNP) surface, which can fold into a G-quadruplex to protect the AuNPs from the aggregation. The developed simple and sensitive colorimetric assay can measure telomerase activity down to 1 HeLa cell uL(-1). More importantly, this assay can be easily extended to high-throughput and automatic format. The AuNP-TS method is PCR-free and therefore avoids the amplification-related errors and becomes more reliable to evaluate telomerase activity. This assay has also been used for initial screening of telomerase inhibitors as anticancer drug agents. PMID- 22083965 TI - A general strategy for the perfluoroalkylation of arenes and arylbromides by using arylboronate esters and [(phen)CuR(F)]. AB - A versatile method for the synthesis of aryl perfluoroalkanes from arenes and aryl bromides is described. Substituted arenes or aryl bromides are converted in situ to an aryl boronate ester that readily undergoes perfluoroalkylation in air with [(phen)CuR(F)]. A broad range of aryl bromide substrates were perfluoroalkylated in good yield for the first time. [(phen)CuCF(3)] is now commercially available and has been prepared on 20 g scale. PMID- 22083966 TI - Concise review: Multidimensional regulation of the hematopoietic stem cell state. AB - Hematopoietic stem cells (HSCs) are characterized by their unique function to produce all lineages of blood cells throughout life. Such tissue-specific function of HSC is attributed to their ability to execute self-renewal and multilineage differentiation. Accumulating evidence indicates that the undifferentiated state of HSC is characterized by dynamic maintenance of chromatin structures and epigenetic plasticity. Conversely, quiescence, self renewal, and differentiation of HSCs are dictated by complex regulatory mechanisms involving specific transcription factors and microenvironmental crosstalk between stem cells and multiple compartments of niches in bone marrows. Thus, multidimensional regulatory inputs are integrated into two opposing characters of HSCs-maintenance of undifferentiated state analogous to pluripotent stem cells but execution of tissue-specific hematopoietic functions. Further studies on the interplay of such regulatory forces as "cell fate determinant" will likely shed the light on diverse spectrums of tissue-specific stem cells. PMID- 22083964 TI - Biological responses of human mesenchymal stem cells to titanium wear debris particles. AB - Wear debris-induced osteolysis is a major cause of orthopedic implant aseptic loosening, and various cell types, including macrophages, monocytes, osteoblasts, and osteoclasts, are involved. We recently showed that mesenchymal stem/osteoprogenitor cells (MSCs) are another target, and that endocytosis of titanium (Ti) particles causes reduced MSC proliferation and osteogenic differentiation. Here we investigated the mechanistic aspects of the endocytosis mediated responses of MSCs to Ti particulates. Dose-dependent effects were observed on cell viability, with doses >300 Ti particles/cell resulting in drastic cell death. To maintain cell viability and analyze particle-induced effects, doses <300 particles/cell were used. Increased production of interleukin 8 (IL-8), but not IL-6, was observed in treated MSCs, while levels of TGF-beta, IL-1beta, and TNF-alpha were undetectable in treated or control cells, suggesting MSCs as a likely major producer of IL-8 in the periprosthetic zone. Disruptions in cytoskeletal and adherens junction organization were also observed in Ti particles-treated MSCs. However, neither IL-8 and IL-6 treatment nor conditioned medium from Ti particle-treated MSCs failed to affect MSC osteogenic differentiation. Among other Ti particle-induced cytokines, only GM-CSF appeared to mimic the effects of reduced cell viability and osteogenesis. Taken together, these results strongly suggest that MSCs play both responder and initiator roles in mediating the osteolytic effects of the presence of wear debris particles in periprosthetic zones. PMID- 22083967 TI - A novel in situ probe for oxygen uptake rate measurement in mammalian cell cultures. AB - The newly developed in situ oxygen uptake rate (in situ OUR) probe presented in this article is based on the in situ microscope technology platform. It is designed to measure the oxygen uptake rate (OUR) of mammalian cells, an important parameter for metabolic flux analysis, inside a reactor (in situ) and in real time. The system isolates a known volume of cell culture from the bulk inside the bioreactor, monitors the oxygen consumption over time, and releases the sample again. The sample is mixed during the measurement with a new agitation system to keep the cells in suspension and prevent oxygen concentration gradients. The OUR measurement system also doubles as a standard dissolved oxygen (DO) probe for process monitoring when it is not performing OUR measurements. It can be equipped with two different types of optical sensors (i.e., DO, pH) simultaneously or a conventional polarographic DO-probe (Clark type). This new probe was successfully tested in baby hamster kidney perfusion cell cultures. PMID- 22083968 TI - Concurrent chemoradiation for adenoid cystic carcinoma of the head and neck. AB - BACKGROUND: We performed a retrospective review of patients with nonresected head and neck adenoid cystic carcinoma (ACC) treated with concurrent chemoradiation. METHODS: Sixteen patients (nasopharynx 7, oropharynx 4, trachea 3, oral and nasal cavity 1 each) were treated at 3 tertiary care centers. Six patients received intraarterial cisplatin and 10 received intravenous cisplatin or carboplatin concurrently with radiation. RESULTS: Thirteen patients are alive, 7 without signs of disease with a median follow-up of 61 months. Tumor progression was noted in 8 patients (50%) (distant metastasis in 5 patients and local tumor progression in 3 patients) with a median time to progression of 25 months (range, 4-52 months). Overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) rates at 5 years were 87%, 39%, and 61%, respectively. CONCLUSION: Concurrent chemoradiation is a feasible treatment option and may lead to sustained locoregional tumor control in patients with nonresected ACC of the head and neck. PMID- 22083970 TI - Asymmetric synthesis of tetrahydroquinolines with quaternary stereocenters through the Povarov reaction. AB - The asymmetric Povarov reaction with alpha-alkyl styrenes as dienophiles was catalyzed by an N,N'-dioxide L4-Sc(OTf)(3) complex. Enantiopure tetrahydroquinoline derivatives with a quaternary stereocenter at the C4 position were synthesized for the first time. A wide variety of alpha-alkyl styrenes and N aryl aldimines were tolerated in the reaction, to give excellent diastereo- (up to 99:1 d.r.) and enantioselectivities (92 to >99% ee). In addition, the reaction could be performed on the gram scale without any loss of yield, diastereoselectivity, or enantioselectivity. An intermolecular hydrogen-shift reaction was found to be a side reaction, which offered a method to synthesize the corresponding quinoline derivatives with chiral quaternary sterocenters. PMID- 22083971 TI - Preparative isolation and purification of antioxidative diarylheptanoid derivatives from Alnus japonica by high-speed counter-current chromatography. AB - This study employed the online HPLC-2,2'-azino-bis(3-ethylbenzthiazoline-6 sulphonic acid) (ABTS)(+) bioassay to rapidly determine the antioxidant compounds occurring in the crude extract of Alnus japonica. The negative peaks of the ABTS(+) radical scavenging detection system, which indicated the presence of antioxidant activity, were monitored by measuring the decrease in absorbance at 734 nm. The ABTS(+)-based antioxidant activity profile showed that three negative peaks exhibited antioxidant activity. High-speed counter-current chromatography (HSCCC) was used for preparative scale separation of the three active peaks from the extract. The purity of the isolated compounds was analyzed by HPLC and their structures were identified by (1)H- and (13)C-nuclear magnetic resonance spectrometry (NMR), heteronuclear multiple bond correlation (HMBC), and heteronuclear single quantum correlation (HSQC). Two solvent systems composed of n-hexane/ethylacetate/methanol/water (4:6:4:6, v/v) and of ethyl acetate/methanol/water (1:0.1:1, v/v) were performed in high-speed counter current chromatography. Consequently, a total of 527 mg of hirsutanonol 5-O-beta D-glucopyranoside, 80.04 mg of 3-deoxohirsutenonol 5-O-beta-D-glucopyranoside, and 91.0 mg of hirsutenone were obtained with purity of 94.7, 90.5, and 98.6%, respectively. PMID- 22083972 TI - Failure characteristics of the isolated distal radius in response to dynamic impact loading. AB - We examined the mechanical response of the distal radius pre-fracture and at fracture under dynamic impact loads. The distal third of eight human cadaveric radii were potted and placed in a custom designed pneumatic impact system. The distal intra-articular surface of the radius rested against a model scaphoid and lunate, simulating 45 degrees of wrist extension. The scaphoid and lunate were attached to a load cell that in turn was attached to an impact plate. Impulsive impacts were applied at increasing energy levels, in 10 J increments, until fracture occurred. Three 45 degrees stacked strain gauge rosettes were affixed along the length of the radius quantifying the bone strains. The mean (SD) fracture energy was 45.5 (16) J. The mean (SD) resultant impact reaction force (IRFr) at failure was 2,142 (1,229) N, resulting in high compressive strains at the distal (2,718 (1,698) uepsilon) and proximal radius (3,664 (1,890) uepsilon). We successfully reproduced consistent fracture patterns in response to dynamic loads. The fracture energy and forces reported here are lower and the strains are higher than those previously reported and can likely be attributed to the controlled, incremental, dynamic nature of the applied loads. PMID- 22083969 TI - Enantioselective decarboxylative alkylation reactions: catalyst development, substrate scope, and mechanistic studies. AB - alpha-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic beta-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID- 22083973 TI - Copper-catalyzed borylation reactions of alkynes and arynes. PMID- 22083974 TI - In vivo fate mapping identifies mesenchymal progenitor cells. AB - Adult mesenchymal progenitor cells have enormous potential for use in regenerative medicine. However, the true identity of the progenitors in vivo and their progeny has not been precisely defined. We hypothesize that cells expressing a smooth muscle alpha-actin promoter (alphaSMA)-directed Cre transgene represent mesenchymal progenitors of adult bone tissue. By combining complementary colors in combination with transgenes activating at mature stages of the lineage, we characterized the phenotype and confirmed the ability of isolated alphaSMA(+) cells to progress from a progenitor to fully mature state. In vivo lineage tracing experiments using a new bone formation model confirmed the osteogenic phenotype of alphaSMA(+) cells. In vitro analysis of the in vivo labeled SMA9(+) cells supported their differentiation potential into mesenchymal lineages. Using a fracture-healing model, alphaSMA9(+) cells served as a pool of fibrocartilage and skeletal progenitors. Confirmation of the transition of alphaSMA9(+) progenitor cells to mature osteoblasts during fracture healing was assessed by activation of bone-specific Col2.3emd transgene. Our findings provide a novel in vivo identification of defined population of mesenchymal progenitor cells with active role in bone remodeling and regeneration. PMID- 22083975 TI - Use of computational fluid dynamics as a tool for establishing process design space for mixing in a bioreactor. AB - The concept of "design space" plays an integral part in implementation of quality by design for pharmaceutical products. ICH Q8 defines design space as "the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post-approval change process. Design space is proposed by the applicant and is subject to regulatory assessment and approval." Computational fluid dynamics (CFD) is increasingly being used as a tool for modeling of hydrodynamics and mass transfer. In this study, a laboratory-scale aerated bioreactor is modeled using CFD. Eulerian-Eulerian multiphase model is used along with dispersed k-epsilon turbulent model. Population balance model is incorporated to account for bubble breakage and coalescence. Multiple reference frame model is used for the rotating region. We demonstrate the usefulness of CFD modeling for evaluating the effects of typical process parameters like impeller speed, gas flow rate, and liquid height on the mass transfer coefficient (k(L)a). Design of experiments is utilized to establish a design space for the above mentioned parameters for a given permissible range of k(L)a. PMID- 22083976 TI - Copolymers comprising 2,7-carbazole and bis-benzothiadiazole units for bulk heterojunction solar cells. AB - On the basis of theoretical considerations of the intramolecular charge transfer (ICT) effect, we have designed a series of donor (D)-acceptor (A) conjugated polymers based on bis-benzothiadiazole (BBT). A PPP-type copolymer of electron rich 2,7-carbazole (CZ) and electron-deficient BBT units poly[N-(2 decyltetradecyl)-2,7-carbazole-co-7,7'-{4,4'-bis-(2,1,3-benzothiadiazole)}] (PCZ BBT), a PPV-type copolymer poly[N-(2-decyltetradecyl)-2,7-carbazolevinylene-co 7,7'-{4,4'-bis-(2,1,3-benzothiadiazolevinylene)}] (PCZV-BBTV), and a tercopolymer based on carbazole, thiophene, and BBT poly[N-(2-decyltetradecyl)-2,7-(di-2 thienyl)carbazole-co-7,7'-{4,4'-bis-(2,1,3-benzothiadiazole)}] (PDTCZ-BBT) have been synthesized to understand the influence of BBT acceptor structure and linkage on the photovoltaic characteristics of the resulting materials. Both the HOMO and LUMO of the resulting polymers are found to be deeper-lying than those of benzothiadiazole-based polymers. The measured electrochemical band gaps (eV) are in the following order: PDTCZ-BBT (1.65 eV) < PCZV-BBTV (1.69 eV) < PCZ-BBT (1.75 eV). All the polymers provide a photovoltaic response when blended with a fullerene derivative as an electron acceptor. The best cell reaches a power conversion efficiency of 2.07 % estimated under standard solar light conditions (AM1.5G, 100 mW cm(-2)). We demonstrate for the first time that BBT-based polymers are promising materials for use in bulk-heterojunction solar cells. PMID- 22083978 TI - An unusual organoyttrium alkyl complex containing a [C5HMe3(eta(3)-CH2)-C5H4N kappa]- ligand and an elusive cyclopentadienide-based scandium tuck-over zwitterion obtained by C-H bond activation. AB - The acid-base reaction between Y(CH(2)SiMe(3))(3)(thf)(2) and the pyridyl functionalized cyclopentadienyl (Cp) ligand C(5)Me(4)H-C(5)H(4)N (1 equiv) at 0 degrees C afforded a mixture of two products: (eta(5):kappa-C(5)Me(4) C(5)H(4)N)Y(CH(2)SiMe(3))(2)(thf) (1 a) and (eta(5):kappa-C(5)Me(4) C(5)H(4)N)(2)YCH(2)SiMe(3) (1 b), in a 5:2 ratio. Addition of the same ligand (2 equiv) to Y(CH(2)SiMe(3))(3)(thf)(2), however, generated 1 b together with the novel complex 1 c, the first well defined yttrium mono(alkyl) complex (eta(5):kappa-C(5)Me(4)-C(5)H(4)N)[C(5)HMe(3)(eta(3)-CH(2))-C(5)H(4)N kappa]Y(CH(2)SiMe(3)) containing a rare kappa/eta(3)-allylic coordination mode in which the C-H bond activation occurs unexpectedly with the allylic methyl group rather than conventionally on Cp ring. If the central metal was changed to lutetium, the equimolar reaction between Lu(CH(2)SiMe(3))(3)(thf)(2) and C(5)Me(4)H-C(5)H(4)N exclusively afforded the bis(alkyl) product (eta(5):kappa C(5)Me(4)-C(5)H(4)N)Lu(CH(2)SiMe(3))(2)(thf) (2 a). Similarly, the reaction between the ligand (2 equiv) and Lu(CH(2)SiMe(3))(3)(thf)(2) gave the mono(alkyl) complex (eta(5):kappa-C(5)Me(4)-C(5)H(4)N)(2)LuCH(2)SiMe(3) (2 b), in which no ligand redistribution was observed. Strikingly, treatment of Sc(CH(2)SiMe(3))(3)(thf)(2) with C(5)Me(4)H-C(5)H(4)N in either 1:1 or 1:2 ratio at 0 degrees C generated the first cyclopentadienide-based scandium zwitterionic "tuck-over" complex 3, (eta(5):kappa-C(5)Me(4)-C(5)H(4)N)Sc(thf)[MU eta(5):eta(1):kappa-C(5)Me(3)(CH(2))-C(5)H(4)N]Sc(CH(2)SiMe(3))(3). In the zwitterion, the dianionic ligand [C(5)Me(3)(CH(2))-C(5)H(4)N](2-) binds both to Sc1(3+) and to Sc2(3+), in eta(5) and eta(1)/kappa modes. In addition, the reaction chemistry, the molecular structures, and the mechanism are also discussed in detail. PMID- 22083977 TI - Novel germline CDKN2A mutation associated with head and neck squamous cell carcinomas and melanomas. AB - BACKGROUND: The ability to identify individuals at increased risk of cancer is of immediate clinical relevance. Germline mutations in the CDKN2A locus, encoding the key tumor suppressor proteins p16/INK4A and p14/ARF, are frequently present in kindreds with hereditary cutaneous melanoma but have seldom been reported in families with genetic susceptibility to head and neck squamous cell carcinomas (HNSCC). METHODS: We report the pedigree of a patient with an unusually high incidence of HNSCC and melanomas. CDKN2A mutation analysis was performed with standard capillary sequencing and multiplex ligation-dependent probe amplification. RESULTS: A previously unreported germline CDKN2A mutation affecting only the p16/INK4A open reading frame, c.106delG (p.Ala36ArgfsX17), was detected in the proband. This mutation causes a premature termination codon. CONCLUSIONS: Our report emphasizes the need to consider germinal CDKN2A mutations in the differential diagnosis of familial HNSCC and the importance of awareness of these tumors in carriers of CDKN2A mutations. PMID- 22083979 TI - Guest-responsive fluorescence of inclusion crystals with pi-stacked supramolecular beads. PMID- 22083980 TI - Enlightening the past: analytical proof for the use of Pistacia exudates in ancient Egyptian embalming resins. AB - Mastic, the resinous exudate of the evergreen shrub Pistacia lentiscus, is frequently discussed as one of the ingredients used for embalming in ancient Egypt. We show the identification of mastic in ancient Egyptian embalming resins by an unambiguous assignment of the mastic triterpenoid fingerprint consisting of moronic acid, oleanonic acid, isomasticadienonic and masticadienonic acid through the consolidation of NMR and GC/MS analysis. Differences in the observed triterpenoid fingerprints between mummy specimens suggest that more than one plant species served as the triterpenoid resin source. Analysis of the triterpenoid acids of ancient embalming resin samples in the form of their methyl and trimethylsilyl esters is compared. In addition we show a simple way to differentiate between residues of mastic from its use as incense during embalming or from direct mastic application in the embalming resin. PMID- 22083981 TI - Traditional Chinese medicine syndrome distribution in chronic hepatitis B populations: a systematic review. AB - Many patients with chronic hepatitis B (CHB) seek help from traditional Chinese medicine (TCM). TCM treatment is based on syndrome differentiation. This study aimed to investigate the syndrome distribution in populations of CHB patients. The pre-specific search strategy was set, and 93 studies (20,106 participants) were identified by electronic and hand searches. The methodological quality of included studies was assessed. Data on syndrome distribution and correlations between syndromes and severity of CHB, were extracted and analyzed. Forty-seven syndromes were identified under 24 different syndrome diagnosis systems for CHB. The majority of included studies reported Liver Depression and Spleen Deficiency (LDSD) (52.54% of studies) or Liver-Gallbladder Dampness Heat (LGDH)/Dampness Heat Obstructing Middle Energizer (DHME) (32.20%) as the major syndromes in CHB patients without cirrhosis. Pooled analysis revealed that LDSD and LGDH/DHME accounted for 61.19% of participants without cirrhosis. In addition, Liver-Kidney Yin Deficiency (LKYinD) (40.99%) and Spleen-Kidney Yang Deficiency (SKYangD) (40.43%) syndromes were common in patients with severe CHB. The percentage of patients with Blood Stasis syndrome increased as the disease progressed to cirrhosis (32.09%). To conclude, LDSD and LGDH/DHME syndromes are found in a significant majority of CHB patients, particularly in the early stages. LKYinD, SKYangD and Blood Stasis dominate in patients at more advanced stages. More epidemiological studies of high methodological quality on syndrome distribution in CHB and standardization of syndrome differentiation for CHB are required to confirm the trends indicated by the studies reviewed here; confirming these trends can increase the efficacy of treatment and give guidance to doctors. PMID- 22083982 TI - Anticancer activity of Nigella sativa (black seed) - a review. AB - Nigella sativa (N. sativa) seed has been an important nutritional flavoring agent and natural remedy for many ailments for centuries in ancient systems of medicine, e.g. Unani, Ayurveda, Chinese and Arabic Medicines. Many active components have been isolated from N. sativa, including thymoquinone, thymohydroquinone, dithymoquinone, thymol, carvacrol, nigellimine-N-oxide, nigellicine, nigellidine and alpha-hederin. In addition, quite a few pharmacological effects of N. sativa seed, its oil, various extracts and active components have been identified to include immune stimulation, anti-inflammation, hypoglycemic, antihypertensive, antiasthmatic, antimicrobial, antiparasitic, antioxidant and anticancer effects. Only a few authors have reviewed the medicinal properties of N. sativa and given some description of the anticancer effects. A literature search has revealed that a lot more studies have been recently carried out related to the anticancer activities of N. sativa and some of its active compounds, such as thymoquinone and alpha-hederin. Acute and chronic toxicity studies have recently confirmed the safety of N. sativa oil and its most abundant active component, thymoquinone, particularly when given orally. The present work is aimed at summarizing the extremely valuable work done by various investigators on the effects of N. sativa seed, its extracts and active principles against cancer. Those related to the underlying mechanism of action, derivatives of thymoquinone, nano thymoquinone and combinations of thymoquinone with the currently used cytotoxic drugs are of particular interest. We hope this review will encourage interested researchers to conduct further preclinical and clinical studies to evaluate the anticancer activities of N. sativa, its active constituents and their derivatives. PMID- 22083983 TI - Applications of nanoparticles in herbal medicine: zedoary turmeric oil and its active compound beta-elemene. AB - Zedoary turmeric oil and its main active ingredient beta-elemene are novel plant derived anticancer agents with long-term clinical application history and low toxicity, which have been approved by the Chinese SFDA to treat different tumors including cancers of the brain, ovary, prostate, breast, lungs, liver, colon, and other tissues. Unfortunately, their hydrophobic properties, poor stabilities and low bioavailabilities seriously hamper their applications in clinic. Therefore, more attention should be paid to develop novel drug delivery systems for zedoary turmeric oil and beta-elemene to enhance their overall quality. Recently, increased research has been carried out on a nanoparticle drug delivery system of zedoary turmeric oil and beta-elemene to solve their poor aqueous solubilities and low bioavailabilities in vivo with much remarkable achievements springing up in the last decade. This review presents the novel nanoparticle formulations of zedoary turmeric oil and beta-elemene and introduces the possible future prospects of their further study. PMID- 22083985 TI - Acupuncture for treatment of noncyclic breast pain: a pilot study. AB - Noncyclic breast pain is a common breast disorder prompting women to seek medical evaluation. We aimed to perform a pilot study on the relief of noncyclic breast pain using acupuncture. Thirty-seven women seen at a diagnostic breast clinic between April 2003 and January 2009 were enrolled. Treatment consisted of four acupuncture sessions over two weeks, with three months of follow-up. Response to treatment was measured with use of a breast pain questionnaire, a quality of life (QOL) questionnaire, and the Cleeland Brief Pain Inventory (BPI) assessed at baseline, end of treatment, and three months after treatment. Data were analyzed using standard descriptive statistics. Twenty-two patients completed four acupuncture sessions. Pain described as throbbing and heavy decreased significantly after acupuncture (p = 0.04 and p = 0.03, respectively). After treatment, pain scores (on the 10-point BPI scale) decreased by an average of 3.5 points for the worst pain during the previous month (p = 0.001), by 2.7 points for average pain (p < 0.001), and by 2.3 points for pain interference (p = 0.002). The percentage of patients reporting a clinically meaningful decrease of 2 points from baseline to the end of treatment included 67% (12/18) for the worst pain, 65% (11/17) for average pain, and 56% (10/18) for pain interference. QOL data showed no improvement in QOL measures (mental, physical, emotional, social, or spiritual well-being). The results of this preliminary study suggest that a randomized controlled trial may be warranted to evaluate the effect of acupuncture on noncyclic breast pain, as well as the optimal frequency of acupuncture treatments. PMID- 22083984 TI - Bioactivity enhancement of herbal supplements by intestinal microbiota focusing on ginsenosides. AB - Intestinal microbiota contribute to diverse mammalian processes including the metabolic functions of drugs. It is a potential new territory for drug targeting, especially for dietary herbal products. Because most herbal medicines are orally administered, the chemical profile and corresponding bioactivities of herbal medicines may be altered by intestinal microbiota. Ginseng is one of the most commonly used herbs and it is an attractive natural product to study its effect in the body. In this review, after briefly introducing the interactions of herbal products and gut microbiota, we discuss the microbiota-mediated metabolism of ginsenosides in ginseng and red ginseng. In particular, the major metabolite compound K and its pharmacological advances are described including anticancer, antidiabetic and anti-inflammatory effects. In summary, the intestinal microbiota may play an important role in mediating the metabolism bioactivity of herbal medicines. PMID- 22083986 TI - Effects of auricular acupuncture on heart rate, oxygen consumption and blood lactic acid for elite basketball athletes. AB - This study investigated the effects of auricular acupuncture on athletes' recovery abilities after exercise. Subjects were selected from twenty-four male elite university basketball players, randomly divided into two groups: auricular acupuncture group (AAG), and normal control group (NCG), each group containing twelve subjects. Auricular acupuncture was experimented to each AAG athlete while no auricular acupuncture was conducted to each NCG athlete. Each subject in both groups performed a ride on the stationary bike until exhausted. The data of heart rate (HR(max)), oxygen consumption (VO(2 max)), and blood lactic acid were measured at four points of time: during the rest period after warm-ups and at the 5th, 30th and 60th minutes post-exercise, respectively. One-way ANOVA and repeated Scheffe methods were used to test the differences of the data between these two groups. The results showed that both HR(max) and blood lactic acid in AAG were significantly lower than those in NCG at the 30th and 60th minutes post exercise. This suggests that auricular acupuncture can enhance athletes' recovery abilities after aggressive exercise. PMID- 22083987 TI - Effect of acupressure in treating urodynamic stress incontinence: a randomized controlled trial. AB - The efficacy of acupressure therapy in managing urodynamic stress incontinence has not been fully investigated. This study evaluates the effects of a validated acupressure protocol for treating women with urodynamic stress incontinence. A randomized, single-blinded, placebo-controlled trial with a before-and-after study design was conducted. Eighty-one women aged between 18 and 60 were recruited at a urogynecology clinic in an acute hospital in Hong Kong. Participants were randomly assigned to an intervention (acupressure) group, a sham group, or a usual care (control) group. A validated acupressure protocol was employed in the intervention group. The intervention comprised three weekly sessions of 30 minutes each for a total of thirty sessions. Outcome measures included pelvic floor muscle strength, number of episodes of urine leakage over four days, self-reported severity of urine leakage, and responses on the Chinese version of the King's Health Questionnaire. No adverse effects were reported. Five percent of the participants dropped out of the study. Intention-to-treat analysis was conducted, the results indicated significant differences in pelvic floor muscle strength across the three groups (H =7.05, p =0.03) and in self reported severity of urine leakage between the intervention and control groups (Z = -2.48, p = 0.01). Significant improvement in all domains of the Chinese version of the King's Health Questionnaire was evident in the intervention group. Acupressure is a simple and non-invasive intervention that appears to have positive physiological and psychological effects on women with urodynamic stress incontinence. The findings support acupressure as an intervention option for managing urodynamic stress incontinence in women. PMID- 22083989 TI - Hot water extracted Lycium barbarum and Rehmannia glutinosa inhibit liver inflammation and fibrosis in rats. AB - Polysaccharide-rich Lycium barbarum and Rehmannia glutinosa have been considered to have immune-modulating activity. This study investigated the effects of water extracted Lycium barbarum and Rehmannia glutinosa (HE) on carbon tetrachloride (CCl(4))-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into: normal diet + peritoneal injection of olive oil (control), normal diet + CCl(4) injection (CCl(4)), 1 * HE (0.05% HE for each) + CCl(4) (1 * HE), and 3 * HE (0.15% HE for each) + CCl(4) (3 * HE) groups. Rats were injected with 40% CCl(4) at a dose of 0.75 ml/kg body weight once a week for seven weeks, one week after herbal extract treatment. After eight week herbal extract treatment, pathohistological examination showed that both 1* and 3 * HE treatments diminished necrotic hepatocytes, chemoattraction of inflammatory cells, and liver fibrosis. Both 1* and 3 * HE treatments decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and reduced hepatic levels of pro-inflammatory cytokines - tumor necrosis factor-alpha and interleukin-1beta - compared to CCl(4) treatment alone. The 1 * HE treatment increased hepatic anti inflammatory cytokine IL-10 levels. Both the 1* and 3 * HE treatments suppressed liver fibrosis biomarkers - transforming growth factor-beta1 and hydroxyproline. Therefore, treatment with water extracted Lycium barbarum and Rehmannia glutinosa (0.05% and 0.15% for each) for eight weeks protects against necrotic damage, indicated by decreases in plasma ALT and AST activities, and suppresses liver fibrosis by down-regulation of liver inflammation in rats with CCl(4)-induced liver injury. PMID- 22083988 TI - Ultra-performance liquid chromatography and time-of-flight mass spectrometry analysis of ginsenoside metabolites in human plasma. AB - American ginseng is a commonly used herbal medicine in the United States. When ginseng is taken orally, its active components, ginsenosides, are reportedly biotransformed by intestinal microbiota. Previous pharmacokinetic evaluations of ginseng in humans have focused on its parent constituents. However, the metabolites, especially those transformed by intestinal microbiota, have not been carefully studied. We used an ultra-performance liquid chromatography/time-of flight mass spectrometry (UPLC/TOF-MS) method to determine 15 ginsenosides and/or metabolites and their bioavailability in humans. Six healthy human subjects received a single oral dose of 10 g of American ginseng root powder, after which samples of their blood were collected at 0, 2, 4, 7, 9 and 12 h for measurement of ginsenoside/metabolite levels in plasma. Ginsenosides Rb1, Rd, Rg2 and compound K (C-K) were detected in human plasma samples at different time points. The Rb1 concentration peak was 19.90 +/- 5.43 ng/ml at 4 h. C-K was detected from 7 h to 12 h with 7.32 +/- 1.35 ng/ml at 12 h. Since the last time point was at 12 h, C-K peak level was not observed. The areas under the concentration curves (AUC) from 0 to 12 h were 155.0 +/- 19.5 ng?h/ml for Rb1 and 26.4 +/- 6.4 ng?h/ml for C-K, respectively. The gradual decrease of Rb1 levels and the delayed increase in levels of C-K observed in human subjects supported previous reports that enteric microbiota played a key role in transforming Rb1 to C-K. PMID- 22083990 TI - Scutellarin attenuates human-neutrophil-elastase-induced mucus production by inhibiting the PKC-ERK signaling pathway in vitro and in vivo. AB - The aim of this study was to investigate the influence of scutellarin on mucus production induced by human neutrophil elastase (HNE) and the possible in vitro and in vivo mechanisms. To this purpose, cells were incubated with saline, scutellarin or gefitinib for 60 min and exposed to 0.1 MUM HNE for 24 h. After being pretreated respectively with saline, scutellarin or gefitinib, rats were challenged intratracheally with HNE by means of nebulization for 30 days. The expression of mucin (MUC) 5AC, protein kinase C (PKC), and extracellular signal regulated kinase 1/2 (ERK1/2) was assessed by ELISA, RT-PCR or Western blotting. The results showed that scutellarin inhibited MUC5AC mRNA and protein expressions induced by HNE in a concentration-dependent manner in vitro. In the in vivo model, scutellarin significantly attenuated MUC5AC mRNA expression and goblet cell hyperplasia in rats treated with HNE for 30 days, as well as decreased the phosporylation of PKC and ERK1/2 compared to the HNE control group. Therefore, our study showed that scutellarin could prevent mucus hypersecretion by inhibiting the PKC-ERK signaling pathway. Inhalation scutellarin may be valuable in the treatment of chronic inflammatory lung disease. PMID- 22083991 TI - Puerarin accelerates peripheral nerve regeneration. AB - This study investigates the effect of puerarin (PR) on peripheral nerve regeneration in vitro and in vivo. PR at concentrations of 1, 10, and 100 MUM significantly promoted survival and outgrowth of cultured Schwann cells, as compared to the controls treated with culture medium only. in vivo study, peripheral nerve regeneration was evaluated across a 15-mm gap in the sciatic nerve of rats using a silicone rubber nerve chamber filled with PR solution. The control group chambers were filled with normal saline only. At the end of eight weeks, animals in the PR groups, especially at a concentration of 1 MUM, had a significantly higher density of myelinated axons, greater evoked action potential area, and a larger nerve conductive velocity, as compared to the controls. All experimental results indicate that PR treatment promotes nerve growth and is a promising herbal medicine for recovery of regenerating peripheral nerves. PMID- 22083992 TI - In vitro activity of Paris polyphylla smith against enterovirus 71 and coxsackievirus B3 and its immune modulation. AB - Enterovirus 71 (EV71) and coxsackievirus B3 (CVB3) have resulted in severe pathogenesis caused by the host's immune response, including the cytokine cascade. Paris polyphylla Smith is a folk medicinal plant in Asia traditionally prescribed for the reduction of pain and elimination of poisoning. In this study, we investigated the anti-EV71 and CVB3 activity of P. polyphylla Smith as well as its immune modulation. The IC(50) for the P. polyphylla Smith 95% ethanol extract against EV71 and CVB3 were 12.5-23% and 99-156% of that of ribavirin, a positive control. Prevention of viral infection, viral inactivation, and anti-viral replication effects against both EV71 and CVB3 were demonstrated by the extract, the anti-viral replication effect being dominant. The extract significantly increased IL-6 production in both EV71- and CVB3-infected cells. A high correlation was possibly demonstrated between the high amounts of IL-6 induction in the EV71 and CVB3-infected cells and the anti-viral replication activity of the extract. In conclusion, good anti-EV71 and CVB3 activity was observed in the P. polyphylla Smith 95% ethanol extract. The high amounts of IL-6 induction in the virus-infected cells played a key role in the anti-viral activity of the extract. PMID- 22083993 TI - Herbal cocktail ka-mi-kae-kyuk-tang stimulates mouse bone marrow stem cell hematopoiesis and janus-activated kinase 2/signal transducer and activator of transcription 5 pathway. AB - Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail. Our collaborative team has shown that it has potent anti-angiogenic, anti-cancer and anti-metastatic activities in vivo without observable side effects. We have documented evidence for KMKKT to alleviate drug-induced hematotoxicity in vivo. In the present study, we investigated the mechanistic and signaling events through which KMKKT enhances hematopoiesis, using hematopoietic stem cells (HSCs) isolated from the bone marrow of 8-12 week-old C57BL/6 mice. Our results show that KMKKT significantly increased the expression of the hematopoietic cytokines interleukin (IL)-3, stem cell factor (SCF), granulocyte-macrophage-colony stimulating factor (GM-CSF), thrombopoietin (TPO) and erythropoietin (EPO) at the level of mRNA and secretion in HSCs. KMKKT also increased the expression of c Kit, a cytokine receptor expressed in HSCs. In addition, KMKKT enhanced phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5), and increased the binding activity of STAT5 to gamma interferon activated sites (GAS) that mediate JAK2 downstream signaling. Furthermore, we found that KMKKT significantly enhanced the growth rate of colony forming unit granulocyte erythrocyte monocyte macrophages (CFU-GEMM) and burst forming unit erythroid (BFU-E) of mouse HSCs (mHSCs) stimulated by IL-3/EPO. Overall, our results demonstrated that KMKKT alleviated drug-induced side effects through enhanced hematopoiesis, at least in part through cytokine-mediated JAK2/STAT5 signaling. PMID- 22083994 TI - Royal jelly reduces melanin synthesis through down-regulation of tyrosinase expression. AB - For cosmetic reasons, the demand for effective and safe skin-whitening agents is high. Since the key enzyme in the melanin synthetic pathway is tyrosinase, many depigmenting agents in the treatment of hyperpigmentation act as tyrosinase inhibitors. In this study, we have investigated the hypo-pigmentary mechanism of royal jelly in a mouse melanocyte cell line, B16F1. Treatment of B16F1 cells with royal jelly markedly inhibited melanin biosynthesis in a dose-dependent manner. Decreased melanin content occurred through the decrease of tyrosinase activity. The mRNA levels of tyrosinase were also reduced by royal jelly. These results suggest that royal jelly reduces melanin synthesis by down-regulation of tyrosinase mRNA transcription and serves as a new candidate in the design of new skin-whitening or therapeutic agents. PMID- 22083995 TI - The chloroform fraction of Solanum nigrum suppresses nitric oxide and tumor necrosis factor-alpha in LPS-stimulated mouse peritoneal macrophages through inhibition of p38, JNK and ERK1/2. AB - Solanum nigrum L., commonly known as black nightshade, is used worldwide for the treatment of skin and mucosal ulcers, liver cirrhosis and edema. We aimed to determine the anti-inflammatory active fraction of S. nigrum by serial extractions. S. nigrum was first extracted with methanol, then fractionated with chloroform and water. The effects of S. nigrum fractions, diosgenin and alpha solanine on LPS/interferon-gamma-induced nitric oxide (NO) and inducible NO synthase (iNOS), or LPS-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, in mouse peritoneal macrophages were determined. Western blotting analysis was used to detect LPS-induced phosphorylation of p38, JNK and ERK1/2. The chloroform fraction of S. nigrum was cytotoxic in a time and concentration dependent manner; however, the methanol and water fractions were not. The chloroform fraction reduced NO through inhibition of iNOS synthesis and inhibited TNF-alpha and IL-6 at the level of protein secretion; the methanol and water fractions showed a weak or no effect. The chloroform fraction also suppressed p38, JNK and ERK1/2. Diosgenin and alpha-solanine were cytotoxic at a high concentration. In particular, diosgenin was able to inhibit TNF-alpha and IL 6, but both compounds did not affect LPS-induced iNOS expression. These results indicate that the anti-inflammatory compounds of S. nigrum exist preferentially in the nonpolar fraction, ruling out the possibility that diosgenin and alpha solanine are the likely candidates. The inhibition of iNOS, TNF-alpha and IL-6 by the chloroform fraction may be partly due to the suppression of p38, JNK and ERK1/2. Further study is required to identify the active compounds of S. nigrum. PMID- 22083996 TI - Antioxidant, anti-inflammatory and antiproliferative activities of Kalanchoe gracilis (L.) DC stem. AB - Oxidative stress and inflammation are related to several chronic diseases including cancer and atherosclerosis. Kalanchoe gracilis (L.) DC is a special folk medicinal plant in Taiwan. The aim of this study was to evaluate the antioxidant, anti-inflammatory and antiproliferative activities of the methanolic extract and fractions of the stem of K. gracilis. TEAC, total phenolic compound content, total flavonoid content, DPPH radical scavenging activity, reducing power, inhibition of NO production in LPS-induced RAW264.7 cells, and inhibition of cancer cell proliferation were analyzed. Among all fractions, the chloroform fraction showed the highest TEAC and DPPH radical scavenging activities. The chloroform fraction also had the highest content of polyphenols and flavonoids. Chloroform fractions also decreased LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. The antiproliferative activities of the methanolic extract and fractions were studied in vitro using HepG2 cells, and the results were consistent with their antioxidant capacities. Chloroform fractions had the highest antiproliferative activity with an IC(50) of 136.85 +/- 2.32 MUg/ml. Eupafolin also had good pharmacological activity in the antioxidant, anti inflammation and antiproliferative. Eupafolin might be an important bioactive compound in the stem of K. gracilis. The above experimental data indicated that the stem of K. gracilis is a potent antioxidant medicinal plant, and such efficacy may be mainly attributed to its polyphenolic compounds. PMID- 22083997 TI - Self-renewal of leukemia stem cells in Friend virus-induced erythroleukemia requires proviral insertional activation of Spi1 and hedgehog signaling but not mutation of p53. AB - Friend virus induces erythroleukemia through a characteristic two-stage progression. The prevailing model proposes that during the initial, polyclonal stage of disease most of the infected cells terminally differentiate, resulting in acute erythrocytosis. In the late stage of disease, a clonal leukemia develops through the acquisition of new mutations--proviral insertional activation of Spi1/Pu.1 and mutation of p53. Previous work from our laboratory demonstrated that Friend virus activates the bone morphogenic protein 4 (BMP4)-dependent stress erythropoiesis pathway, which leads to the rapid expansion of stress erythroid progenitors, which are the targets for Friend virus in the spleen. We recently showed that stress erythroid progenitors have intrinsic self-renewal ability and therefore could function as leukemia stem cells (LSCs) when infected with Friend virus. Here, we show that the two stages of Friend virus-induced disease are caused by infection of distinct stress progenitor populations in the spleen. The development of leukemia relies on the ability of the virus to hijack the intrinsic self-renewal capability of stress erythroid progenitors leading to the generation of LSCs. Two signals are required for the self-renewal of Friend virus LSCs proviral insertional activation of Spi1/Pu.1 and Hedgehog-dependent signaling. Surprisingly, mutation of p53 is not observed in LSCs. These data establish a new model for Friend virus-induced erythroleukemia and demonstrate the utility of Friend virus as a model system to study LSC self-renewal. PMID- 22083999 TI - Microwave-assisted organocatalytic enantioselective intramolecular aza-Michael reaction with alpha,beta-unsaturated ketones. AB - An organocatalytic enantioselective intramolecular aza-Michael reaction of carbamates bearing conjugated ketones as Michael acceptors is described. By using 9-amino-9-deoxy-epi-hydroquinine as the catalyst and pentafluoropropionic acid as a co-catalyst, a series of piperidines, pyrrolidines, and the corresponding benzo fused derivatives (indolines, isoindolines, tetrahydroquinolines, and tetrahydroisoquinolines) can be obtained in excellent yields and enantioselectivities. In addition, the use of microwave irradiation at 60 degrees C improves the efficiency of the process giving rise to the final products with comparable yields and enantiomeric excesses. Some mechanistic insights are also considered. PMID- 22083998 TI - Accelerated phase-contrast cine MRI using k-t SPARSE-SENSE. AB - Phase-contrast (PC) cine MRI is a promising method for assessment of pathologic hemodynamics, including cardiovascular and hepatoportal vascular dynamics, but its low data acquisition efficiency limits the achievable spatial and temporal resolutions within clinically acceptable breath-hold durations. We propose to accelerate PC cine MRI using an approach which combines compressed sensing and parallel imaging (k-t SPARSE-SENSE). We validated the proposed 6-fold accelerated PC cine MRI against 3-fold accelerated PC cine MRI with parallel imaging (generalized autocalibrating partially parallel acquisitions). With the programmable flow pump, we simulated a time varying waveform emulating hepatic blood flow. Normalized root mean square error between two sets of velocity measurements was 2.59%. In multiple blood vessels of 12 control subjects, two sets of mean velocity measurements were in good agreement (mean difference = 0.29 cm/s; lower and upper 95% limits of agreement = -5.26 and 4.67 cm/s, respectively). The mean phase noise, defined as the standard deviation of the phase in a homogeneous stationary region, was significantly lower for k-t SPARSE SENSE than for generalized autocalibrating partially parallel acquisitions (0.05 +/- 0.01 vs. 0.19 +/- 0.06 radians, respectively; P < 0.01). The proposed 6-fold accelerated PC cine MRI pulse sequence with k-t SPARSE-SENSE is a promising investigational method for rapid velocity measurement with relatively high spatial (1.7 mm * 1.7 mm) and temporal (~35 ms) resolutions. PMID- 22084000 TI - Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis. AB - The aim of this study is to find the potential biomarkers from the rat hepatocellular carcinoma (HCC) disease model by using a non-target metabolomics method, and test their usefulness in early human HCC diagnosis. The serum metabolic profiling of the diethylnitrosamine-induced rat HCC model, which presents a stepwise histopathological progression that is similar to human HCC, was performed using liquid chromatography-mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. Three metabolites, taurocholic acid, lysophosphoethanolamine 16:0, and lysophosphatidylcholine 22:5, were defined as "marker metabolites," which can be used to distinguish the different stages of chemical hepatocarcinogenesis. These metabolites represented the abnormal metabolism during the progress of hepatocarcinogenesis, which could also be found in patients. To test their diagnosis potential 412 sera from 262 patients with HCC, 76 patients with cirrhosis and 74 patients with chronic hepatitis B were collected and studied, it was found that 3 marker metabolites were effective for the discrimination of small liver tumor (solitary nodules of less than 2 cm in diameter) patients, achieved a sensitivity of 80.5% and a specificity of 80.1%,which is better than those of alpha-fetoprotein (53 and 64%, respectively). Moreover, they were also effective for the discrimination of all HCCs and chronic liver disease patients, which could achieve a sensitivity of 87.5% and a specificity of 72.3%, better than those of alpha-fetoprotein (61.2 and 64%). These results indicate metabolomics method has the potential of finding biomarkers for the early diagnosis of HCC. PMID- 22084001 TI - Cryogun cryotherapy for oral leukoplakia. AB - BACKGROUND: Our previous study showed that cotton-swab cryotherapy is an alternative treatment modality for oral leukoplakia. METHODS: This study used liquid nitrogen spray with a cryogun (cryogun cryotherapy) to treat 60 oral leukoplakia lesions. RESULTS: Complete regression was achieved in all 60 oral leukoplakia lesions after cryogun cryotherapy. We found that 60 oral leukoplakia lesions treated with cryogen cryotherapy needed significantly fewer mean treatments (3.1 +/- 1.3) to achieve complete regression than 60 previously reported oral leukoplakia lesions treated with cotton-swab cryotherapy (mean, 6.3 +/- 3.8 treatments). Oral leukoplakia lesions on oral mucosal sites other than the tongue, <2 cm(2) , with epithelial dysplasia, or with a surface keratin thickness <55 MUm required significantly fewer cryogun cryotherapy treatments to achieve complete regression. CONCLUSIONS: For treatment of oral leukoplakia, the cryogun cryotherapy needed fewer mean treatments to achieve complete regression of the lesions than the cotton-swab cryotherapy. PMID- 22084002 TI - Conformational and electronic consequences in crafting extended, pi-conjugated, light-harvesting macrocycles. AB - The synthesis of a new series of free-base, Ni(II) and Zn(II) 2,3,12,13 tetra(ethynyl)-5,10,15,20-tetraphenyl porphyrins is described. Upon heating, two of the four ethynyl moieties undergo Bergman cyclization to afford the monocyclized 2,3-diethynyl-5,20-diphenylpiceno[10,11,12,13,14,15-jklmn]porphyrin in 30 %, 10 %, and trace yields, respectively. The structures of all products were investigated by using quantum chemical calculations and the free-base analogue was isolated and crystallized; all compounds show significant deviation from the idealized planar structure. No fully-cyclized bispiceno[20,1,2,3,4,5,10,11,12,13,14,15-fghij]porphyrin was isolated from the reaction mixture. To understand why only two of the four enthynyl groups undergo Bergman cyclization, the reaction coordinates were examined by using DFT at the PWPW91/cc-pVTZ(-f) level coupled to a continuum solvation model. The barrier to cyclization of the second pair of ethynyl groups was found to be 5.5 kcal mol( 1) higher than the first, suggesting a negative cooperative effect and significantly slower rate for the second cyclization. Cyclization reactions for model porphyrin-enediynes with ethene- and H-functionality substitutions at the meso-phenyl rings were also examined, and found to have a similar barrier to diradical formation for the second cyclization event as for the first in these highly planar molecules. By enforcing an artificial 30 degrees cant in two of the pyrrole rings of the porphyrin, the second barrier was increased by 2 kcal mol(-1) in the ethene model system; this suggests that the disruption of the pi conjugation of the extended porphyrin structure is the cause of the increased barrier to the second cyclization event. PMID- 22084005 TI - HILIC-MS/MS method development for targeted quantitation of metabolites: practical considerations from a clinical diagnostic perspective. AB - The development of targeted assays for polar molecules is a persistent challenge in quantitative metabolite measurement. In addressing these challenges, hydrophilic interaction liquid chromatography (HILIC) has proved to be a valuable, though under-used and poorly understood chromatographic technique. This work has addressed a number of components that are intrinsic in development of a high-throughput, specific and sensitive assay for metabolites using HILIC-MS/MS. Generally accepted HILIC doctrine, such as addition of water to all mobile phases and re-equilibration time, was shown to be flawed under gradient HILIC mode. The effect of non-classical mobile phase additives on HILIC-MS/MS specificity, sensitivity and assay throughput was shown for endogenous metabolites. A broad evaluation of columns and mobile phases for the retention of varied molecular classes was performed, elucidating the empirical nature of HILIC method development. Application of the empirical evaluations performed in the paper was demonstrated by detailing a method development cycle for methylmalonic acid to achieve a highly selective and sensitive HILIC-MS/MS quantitation capable of high throughput analysis for clinical utility. PMID- 22084006 TI - Reduced resolution transit delay prescan for quantitative continuous arterial spin labeling perfusion imaging. AB - Arterial spin labeling perfusion MRI can suffer from artifacts and quantification errors when the time delay between labeling and arrival of labeled blood in the tissue is uncertain. This transit delay is particularly uncertain in broad clinical populations, where reduced or collateral flow may occur. Measurement of transit delay by acquisition of the arterial spin labeling signal at many different time delays typically extends the imaging time and degrades the sensitivity of the resulting perfusion images. Acquisition of transit delay maps at the same spatial resolution as perfusion images may not be necessary, however, because transit delay maps tend to contain little high spatial resolution information. Here, we propose the use of a reduced spatial resolution arterial spin labeling prescan for the rapid measurement of transit delay. Approaches to using the derived transit delay information to optimize and quantify higher resolution continuous arterial spin labeling perfusion images are described. Results in normal volunteers demonstrate heterogeneity of transit delay across different brain regions that lead to quantification errors without the transit maps and demonstrate the feasibility of this approach to perfusion and transit delay quantification. PMID- 22084007 TI - Sequential linear neighborhood propagation for semi-supervised protein function prediction. AB - Predicting protein function is one of the most challenging problems of the post genomic era. The development of experimental methods for genome scale analysis of molecular interaction networks has provided new approaches to inferring protein function. In this paper we introduce a new graph-based semi-supervised classification algorithm Sequential Linear Neighborhood Propagation (SLNP), which addresses the problem of the classification of partially labeled protein interaction networks. The proposed SLNP first constructs a sequence of node sets according to their shortest distance to the labeled nodes, and then predicts the function of the unlabel proteins from the set closer to labeled one, using Linear Neighborhood Propagation. Its performance is assessed on the Saccharomyces cerevisiae PPI network data sets, with good results compared with three current state-of-the-art algorithms, especially in settings where only a small fraction of the proteins are labeled. PMID- 22084008 TI - A graph-based semantic similarity measure for the gene ontology. AB - Existing methods for calculating semantic similarities between pairs of Gene Ontology (GO) terms and gene products often rely on external databases like Gene Ontology Annotation (GOA) that annotate gene products using the GO terms. This dependency leads to some limitations in real applications. Here, we present a semantic similarity algorithm (SSA), that relies exclusively on the GO. When calculating the semantic similarity between a pair of input GO terms, SSA takes into account the shortest path between them, the depth of their nearest common ancestor, and a novel similarity score calculated between the definitions of the involved GO terms. In our work, we use SSA to calculate semantic similarities between pairs of proteins by combining pairwise semantic similarities between the GO terms that annotate the involved proteins. The reliability of SSA was evaluated by comparing the resulting semantic similarities between proteins with the functional similarities between proteins derived from expert annotations or sequence similarity. Comparisons with existing state-of-the-art methods showed that SSA is highly competitive with the other methods. SSA provides a reliable measure for semantics similarity independent of external databases of functional annotation observations. PMID- 22084009 TI - Using binding profiles to predict binding sites of target RNAs. AB - Prediction of RNA-RNA interaction is a key to elucidating possible functions of small non-coding RNAs, and a number of computational methods have been proposed to analyze interacting RNA secondary structures. In this article, we focus on predicting binding sites of target RNAs that are expected to interact with regulatory antisense RNAs in a general form of interaction. For this purpose, we propose bistaRNA, a novel method for predicting multiple binding sites of target RNAs. bistaRNA employs binding profiles that represent scores for hybridized structures, leading to reducing the computational cost for interaction prediction. bistaRNA considers an ensemble of equilibrium interacting structures and seeks to maximize expected accuracy using dynamic programming. Experimental results on real interaction data validate good accuracy and fast computation time of bistaRNA as compared with several competitive methods. Moreover, we aim to find new targets given specific antisense RNAs, which provides interesting insights into antisense RNA regulation. bistaRNA is implemented in C++. The program and Supplementary Material are available at http://rna.naist.jp/program/bistarna/. PMID- 22084010 TI - A new genotype calling method for affymetrix SNP arrays. AB - Current genotype-calling methods such as Robust Linear Model with Mahalanobis Distance Classifier (RLMM) and Corrected Robust Linear Model with Maximum Likelihood Classification (CRLMM) provide accurate calling results for Affymetrix Single Nucleotide Polymorphisms (SNP) chips. However, these methods are computationally expensive as they employ preprocess procedures, including chip data normalization and other sophisticated statistical techniques. In the small sample case the accuracy rate may drop significantly. We develop a new genotype calling method for Affymetrix 100 k and 500 k SNP chips. A two-stage classification scheme is proposed to obtain a fast genotype calling algorithm. The first stage uses unsupervised classification to quickly discriminate genotypes with high accuracy for the majority of the SNPs. And the second stage employs a supervised classification method to incorporate allele frequency information either from the HapMap data or from a self-training scheme. Confidence score is provided for every genotype call. The overall performance is shown to be comparable to that of CRLMM as verified by the known gold standard HapMap data and is superior in small sample cases. The new algorithm is computationally simple and standalone in the sense that a self-training scheme can be used without employing any other training data. A package implementing the calling algorithm is freely available at http://www.sfs.ecnu.edu.cn/teachers/xuj_en.html. PMID- 22084011 TI - Verification of phylogenetic inference programs using metamorphic testing. AB - Many phylogenetic inference programs are available to infer evolutionary relationships among taxa using aligned sequences of characters, typically DNA or amino acids. These programs are often used to infer the evolutionary history of species. However, in most cases it is impossible to systematically verify the correctness of the tree returned by these programs, as the correct evolutionary history is generally unknown and unknowable. In addition, it is nearly impossible to verify whether any non-trivial tree is correct in accordance to the specification of the often complicated search and scoring algorithms. This difficulty is known as the oracle problem of software testing: there is no oracle that we can use to verify the correctness of the returned tree. This makes it very challenging to test the correctness of any phylogenetic inference programs. Here, we demonstrate how to apply a simple software testing technique, called Metamorphic Testing, to alleviate the oracle problem in testing phylogenetic inference programs. We have used both real and randomly generated test inputs to evaluate the effectiveness of metamorphic testing, and found that metamorphic testing can detect failures effectively in faulty phylogenetic inference programs with both types of test inputs. PMID- 22084012 TI - JAGUC--a software package for environmental diversity analyses. AB - BACKGROUND: The study of microbial diversity and community structures heavily relies on the analyses of sequence data, predominantly taxonomic marker genes like the small subunit of the ribosomal RNA (SSU rRNA) amplified from environmental samples. Until recently, the "gold standard" for this strategy was the cloning and Sanger sequencing of amplified target genes, usually restricted to a few hundred sequences per sample due to relatively high costs and labor intensity. The recent introduction of massive parallel tag sequencing strategies like pyrosequencing (454 sequencing) has opened a new window into microbial biodiversity research. Due to its swift nature and relatively low expense, this strategy produces millions of environmental SSU rDNA sequences granting the opportunity to gain deep insights into the true diversity and complexity of microbial communities. The bottleneck, however, is the computational processing of these massive sequence data, without which, biologists are hardly able to exploit the full information included in these sequence data. RESULTS: The freely available standalone software package JAGUC implements a broad regime of different functions, allowing for efficient and convenient processing of a huge number of sequence tags, including importing custom-made reference data bases for basic local alignment searches, user-defined quality and search filters for analyses of specific sets of sequences, pairwise alignment-based sequence similarity calculations and clustering as well as sampling saturation and rank abundance analyses. In initial applications, JAGUC successfully analyzed hundreds of thousands of sequence data (eukaryote SSU rRNA genes) from aquatic samples and also was applied for quality assessments of different pyrosequencing platforms. CONCLUSIONS: The new program package JAGUC is a tool that bridges the gap between computational and biological sciences. It enables biologists to process large sequence data sets in order to infer biological meaning from hundreds of thousands of raw sequence data. JAGUC offers advantages over available tools which are further discussed in this manuscript. PMID- 22084013 TI - Comparison of two academic software packages for analyzing two-dimensional gel images. AB - One of the key limitations for proteomic studies using two-dimensional (2D) gel is the lack of automatic, fast, robust, and reliable methods for detecting, matching, and quantifying protein spots. Although there are commercial software packages for 2D gel image analysis, extensive human intervention is still needed for spot detection and matching, which is time-consuming and error-prone. Moreover, the commercial software packages are usually expensive and non-open source. Thus, it is very beneficial for researchers to have free software that is fast, fully automatic, and robust. In this paper, we review and compare two recently developed and publicly available software packages, RegStatGel and Pinnacle, for analyzing 2D gel images. These two software packages share some common features and also have some fundamental difference in the aspects of spot detection and quantification. Based on our experience, RegStatGel is much better in terms of spot detection and matching. It also contains more advanced statistical tools and is more user-friendly. In contrast, Pinnacle is quite sensitive to background noise and relies on external statistical software packages for statistical analysis. PMID- 22084014 TI - How to choose a normalization strategy for miRNA quantitative real-time (qPCR) arrays. AB - Low-density arrays for quantitative real-time PCR (qPCR) are increasingly being used as an experimental technique for miRNA expression profiling. As with gene expression profiling using microarrays, data from such experiments needs effective analysis methods to produce reliable and high-quality results. In the pre-processing of the data, one crucial analysis step is normalization, which aims to reduce measurement errors and technical variability among arrays that might have arisen during the execution of the experiments. However, there are currently a number of different approaches to choose among and an unsuitable applied method may induce misleading effects, which could affect the subsequent analysis steps and thereby any conclusions drawn from the results. The choice of normalization method is hence an important issue to consider. In this study we present the comparison of a number of data-driven normalization methods for TaqMan low-density arrays for qPCR and different descriptive statistical techniques that can facilitate the choice of normalization method. The performance of the normalization methods was assessed and compared against each other as well as against standard normalization using endogenous controls. The results clearly show that the data-driven methods reduce variation and represent robust alternatives to using endogenous controls. PMID- 22084015 TI - Hierarchical mesoporous zeolites: direct self-assembly synthesis in a conventional surfactant solution by kinetic control over the zeolite seed formation. AB - By kinetic control over the zeolite seed formation, we report the direct fabrication of hierarchical mesoporous zeolites using hexadecyl trimethyl ammonium bromide (CTAB) as the soft template in a conventional solution route. Nanometer-sized, subnanocrystal-type zeolite seeds with a high degree of polymerization are essential to prevent the formation of a separate amorphous mesoporous phase and the phase separation between the mesophase and zeolite crystals in the presence of CTAB and a certain amount of ethanol. The mechanisms for the formation of hierarchically porous zeolites in the solution process, including the effect of mother liquid aging, formation of subnanocrystal zeolite seeds and their self-assembly effect with CTAB, and the role of ethanol are proposed and discussed in detail. The prepared mesoporous ZSM-5 zeolite showed much higher catalytic activity than conventional counterparts for aldol condensations involving large molecules, especially in the synthesis of vesidryl. PMID- 22084016 TI - HOXB4 can enhance the differentiation of embryonic stem cells by modulating the hematopoietic niche. AB - Hematopoietic differentiation of embryonic stem cells (ESCs) in vitro has been used as a model to study early hematopoietic development, and it is well documented that hematopoietic differentiation can be enhanced by overexpression of HOXB4. HOXB4 is expressed in hematopoietic progenitor cells (HPCs) where it promotes self-renewal, but it is also expressed in the primitive streak of the gastrulating embryo. This led us to hypothesize that HOXB4 might modulate gene expression in prehematopoietic mesoderm and that this property might contribute to its prohematopoietic effect in differentiating ESCs. To test our hypothesis, we developed a conditionally activated HOXB4 expression system using the mutant estrogen receptor (ER(T2)) and showed that a pulse of HOXB4 prior to HPC emergence in differentiating ESCs led to an increase in hematopoietic differentiation. Expression profiling revealed an increase in the expression of genes associated with paraxial mesoderm that gives rise to the hematopoietic niche. Therefore, we considered that HOXB4 might modulate the formation of the hematopoietic niche as well as the production of hematopoietic cells per se. Cell mixing experiments supported this hypothesis demonstrating that HOXB4 activation can generate a paracrine as well as a cell autonomous effect on hematopoietic differentiation. We provide evidence to demonstrate that this activity is partly mediated by the secreted protein FRZB. PMID- 22084017 TI - Longitudinal analysis of voice quality in patients with early glottic cancer after transoral laser microsurgery. AB - BACKGROUND: We conducted longitudinal voice evaluations in patients with early glottic cancer who underwent transoral laser microsurgery (TLM) to determine the time to stability. METHODS: Twenty-five patients underwent TLM, including 13 limited cordectomies (type I and type II) and 12 extended cordectomies (type III to type IV). Multidimensional voice evaluations were performed before treatment and at 1, 3, 6, and 12 months after treatment. RESULTS: Voice parameters of asthenicity, strain, mean airflow rate (MFR), voice handicap index (VHI) functional, VHI-physical, and VHI-total scores improved in all patients. Most patients had improved 6 months after TLM. Patients with extended cordectomy showed higher breathiness, MFR, VHI-functional, and VHI-total scores. Healing was complete in all cases by 6 months and in a majority of cases (76%) by 3 months. CONCLUSIONS: Voice quality achieved stability 6 months after TLM. Comparing treatment outcomes and surgical intervention are not recommended within 6 months of surgery. PMID- 22084018 TI - A fluorophoric-axle-based, nonfluororescent, metallo anti-[3]pseudorotaxane: recovery of fluorescence by means of an axle substitution reaction. AB - A Cu(2+)-templated, multinuclear, nonfluorescent, anti-[3]pseudorotaxane was synthesized on a fluorophoric axle. The Cu(2+)-templated [3]pseudorotaxane was characterized by the electrospray ionization mass spectroscopy (ESI-MS), UV/Vis and EPR spectroscopy, and single-crystal X-ray data. The ESI-MS showed peaks that support the formation of [3]pseudorotaxane. The UV/Vis spectrum of [3]pseudorotaxane in CH(3)CN showed a characteristic d-d band of a Cu(2+) complex at 650 nm. Further, the X-band in the EPR spectrum of [3]pseudorotaxane suggested a distorted square-pyramidal geometry of Cu(2+). Importantly, formation of the [3]pseudorotaxane was confirmed by the single-crystal X-ray structural analysis, which showed that one fluorophoric axle was threaded into two Cu(2+) macrocyclic wheels (MC-Cu(2+)) with an anti conformation. The UV/Vis and fluorescence titration experiments were carried out to follow the solution-state formation of [3]pseudorotaxane by MC-Cu(2+) and fluorophoric axle in CH(3)CN. In both studies, the sigmoidal curve fit supported the formation of 1:2 complex of the fluorophoric axle and MC-Cu(2+) complex. Secondly, the release of the fluorophoric axle from the nonfluorescent [3]pseudorotaxane through the formation of a [2]pseudorotaxane was demonstrated by titrating a solution of the [3]pseudorotaxane with a stronger bidentate chelating ligand, such as 1,10 phenanthroline (Phen). Substitution of the fluorophoric axle from the [3]pseudorotaxane with about 100% efficiency was achieved by the addition of approximately two equivalents of Phen, and the formation of a Phen-threaded [2]pseudorotaxane was established by ESI-MS of the resulting solution and a single-crystal X-ray study. Axle substitution was also confirmed by a fluorescence titration experiment, which showed a step-wise recovery of the fluorescence intensity of the fluorophoric axle. The association constants for the formation of the [3]- and [2]pseudrotaxanes were calculated from the fluorescence and UV/Vis data. In addition, 2,2'-bipyridine (BPy), which is a relatively weaker bidendate chelating ligand compared to Phen, showed an inefficient and incomplete axle substitution of the [3]pseudorotaxane, although BPy previously showed the formation of [2]pseudrotaxane with the MC-Cu(2+) wheel in solution and ESI-MS studies. In this context, the formation of a BPy-threaded [2]pseudrotaxane was further established by single-crystal X-ray diffraction study. PMID- 22084019 TI - Genetic vs. phenotypic responses of trees to altitude. PMID- 22084020 TI - Growth and physiology of olive pioneer and fibrous roots exposed to soil moisture deficits. AB - In woody plants, pioneer roots are the main roots used to expand the root system horizontally and vertically whereas fibrous 'feeder' roots are chiefly used in the absorption of water and nutrients. Because of their different roles, we expected newly emerged pioneer and fibrous roots to respond differently to restrictions in soil moisture. We hypothesized that fibrous roots would exhibit greater growth plasticity and greater physiological impairment from soil moisture deficits, especially under heterogeneous conditions. We compared the responses of fibrous and pioneer roots of olive seedlings (Olea europaea) to localized and uniform soil moisture deficits in transparent containers in the greenhouse. In comparison with uniformly wet conditions, uniformly dry conditions caused reduced shoot photosynthesis and reduced shoot growth, but no significant effect on root morphology, root respiration (measured in aerated buffer solution using excised roots) or electrolyte leakage as a function of root age. Under heterogeneous soil moisture conditions, root growth tended to preferentially occur in the moist sector, especially in the pioneer roots. In comparison with pioneer roots in the moist sector, pioneer roots in the dry sector had higher tissue density and higher suberin content, but no shift in root respiration, non-structural carbohydrates or electrolyte leakage. In contrast, fibrous roots in the dry sector exhibited evidence of impaired physiology in older (>38 days) roots compared with similar age fibrous roots in the moist sector. While we anticipated that, compared with pioneer roots, fibrous roots would be more sensitive to soil moisture deficits as expressed by higher electrolyte leakage, we did not expect the strong growth plasticity of pioneer roots under heterogeneous soil moisture conditions. Differentiating the responses of these two very different root types can improve our understanding of how different portions of the root system of woody plants cope with soil moisture deficits. PMID- 22084021 TI - Boron nutrition affects the carbon metabolism of silver birch seedlings. AB - Boron (B) is an essential micronutrient whose deficiency is common both in agriculture and in silviculture. Boron deficiency impairs the growth of plants and affects many metabolic processes like carbohydrate metabolism. Boron deficiency and also excess B may decrease the sink demand by decreasing the growth and sugar transport which may lead to the accumulation of carbohydrates and down-regulation of photosynthesis. In this study, we investigated the effects of B nutrition on the soluble and storage carbohydrate concentrations of summer leaves and autumn buds in a deciduous tree species, Betula pendula Roth. In addition, we investigated the changes in the pools of condensed tannins between summer and autumn harvests. One-year-old birch seedlings were fertilized with a complete nutrient solution containing three different levels of B: 0, 30 and 100% of the standard level for complete nutrient solution. Half of the seedlings were harvested after summer period and another half when leaves abscised. The highest B fertilization level (B100) caused an accumulation of starch and a decrease in the concentrations of hexoses (glucose and fructose) in summer leaves, whereas in the B0 seedlings, hexoses (mainly glucose) accumulated and starch decreased. These changes in carbohydrate concentrations might be related to the changes in the sink demand since the autumn growth was the smallest for the B100 seedlings and largest for the B30 seedlings that did not accumulate carbohydrates. The autumn buds of B30 seedlings contained the lowest levels of glucose, glycerol, raffinose and total polyols, which was probably due to the dilution effect of the deposition of other substances like phenols. Condensed tannins accumulated in high amounts in the birch stems during the hardening of seedlings and the largest accumulation was detected in the B30 treatment. Our results suggest that B nutrition of birch seedlings affects the carbohydrate and phenol metabolism and may play an important role in the hardening process of the seedlings. PMID- 22084022 TI - The pathogenic white-rot fungus Heterobasidion parviporum triggers non-specific defence responses in the bark of Norway spruce. AB - Norway spruce [Picea abies (L.) Karst.] is one of the economically most important conifer species in Europe. The major pathogen on Norway spruce is Heterobasidion parviporum (Fr.) Niemela & Korhonen. To achieve a better understanding of Norway spruce's defence mechanisms, transcriptional responses in bark to H. parviporum infection were compared with the response to wounding using cDNA-amplified fragment length polymorphism. The majority of the recovered transcript-derived fragments (TDFs) showed a similar expression pattern for infection and wounding treatment, although inoculated samples showed an enhanced reaction. Genes related to systemic acquired resistance, e.g., PR1, accumulated after H. parviporum infection. Simultaneously, several transcripts involved in various aspects of jasmonic acid (JA)- and ethylene (ET)-mediated signalling accumulated. Genes involved in the ubiquitin/proteasome system were also regulated. Expression patterns have been confirmed by quantitative polymerase chain reaction. The expression patterns of the isolated TDFs suggest that infection with H. parviporum in Norway spruce induces a broad defence, with many similarities to non-specific defence responses in angiosperms. The parallel induction of salicylic acid- and JA/ET-mediated pathways implies spatially separated responses in different cell layers, with and without hyphal contact. A set of TDFs were analysed in an independent experiment with unrelated material treated with wounding or with inoculation with H. parviporum or Phlebiopsis gigantea, verifying the original observations and underlining the non-specific defence responses. In addition, our data suggest that rerouting of carbon in secondary metabolism is an integral part of Norway spruce induced defence. We report the sequences of three 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase genes (PaDAHP1, PaDAHP2 and PaDAHP3) and their relative expression in response to wounding and infection with H. parviporum and P. gigantea. The results clearly indicate differential regulation of the three DAHPs in the induced defence responses in Norway spruce. This study gives insights into the central mechanisms in the induced defences in Norway spruce. PMID- 22084023 TI - Probing the effects of one-electron reduction and protonation on the electronic properties of the Fe-S clusters in the active-ready form of [FeFe]-hydrogenases. A QM/MM investigation. AB - A QM/MM investigation of the active-ready (H(ox)) form of [FeFe]-hydrogenase from D. desulfuricans, in which the electronic properties of all Fe-S clusters (H, F and F') have been simultaneously described using DFT, was carried out with the aim of disclosing a possible interplay between the H-cluster and the accessory iron-sulfur clusters in the initial steps of the catalytic process leading to H(2) formation. It turned out that one-electron addition to the active-ready form leads to reduction of the F'-cluster and not of the H-cluster. Protonation of the H-cluster in H(ox) is unlikely, and in any case it would not trigger electron transfer from the accessory Fe(4)S(4) clusters to the active site. Instead, one electron reduction and protonation of the active-ready form trigger electron transfer within the protein, a key event in the catalytic cycle. In particular, protonation of the H-cluster after one-electron reduction of the enzyme lowers the energy of the lowest unoccupied molecular orbitals localized on the H-cluster to such an extent that a long-range electron transfer from the F'-cluster towards the H-cluster itself is allowed. PMID- 22084024 TI - Separation and purification of isorhamnetin 3-sulphate from Flaveria bidentis (L.) Kuntze by counter-current chromatography comparing two kinds of solvent systems. AB - The first preparative separation of a flavonoid sulphate isorhamnetin 3-sulphate from Flaveria bidentis (L.) Kuntze by counter-current chromatography (CCC) was presented. Two kinds of solvent systems were used. A conventional organic/aqueous solvent system n-butanol-ethyl acetate-water (4:1:5, v/v) was used, yielding isorhamnetin 3-sulphate 2.0 mg with a purity of 93.4% from 83 mg of pre-enriched crude extract obtained from 553 mg ethanol extract by macroporous resin. A one component organic/salt-containing system composed of n-butanol-0.25% sodium chloride aqueous solution (1:1, v/v) was also used, and the LC column packed with macroporous resin has been employed for desalination of the target compound purified from CCC. As a result, 2.1 mg of isorhamnetin 3-sulphate with a purity of over 97% has been isolated from 402 mg of crude extract without pre enrichment. Compared with the conventional organic/aqueous system, the one component organic/salt-containing aqueous system was more suitable for the separation of isorhamnetin 3-sulphate, and purer target compound was obtained from the crude extract without pre-enrichment using the new solvent system. The chemical structure was confirmed by ESI-MS and (1)H, (13)C NMR. In summary, our results indicated that CCC using one-component organic/salt-containing aqueous solution is very promising and powerful for high-throughput purification of isorhamnetin 3-sulphate from Flaveria bidentis (L.) Kuntze. PMID- 22084025 TI - Optically transmitted and inductively coupled electric reference to access in vivo concentrations for quantitative proton-decoupled 13C magnetic resonance spectroscopy. AB - This report describes our efforts on quantification of tissue metabolite concentrations in mM by nuclear Overhauser enhanced and proton decoupled (13) C magnetic resonance spectroscopy and the Electric Reference To access In vivo Concentrations (ERETIC) method. Previous work showed that a calibrated synthetic magnetic resonance spectroscopy-like signal transmitted through an optical fiber and inductively coupled into a transmit/receive coil represents a reliable reference standard for in vivo (1) H magnetic resonance spectroscopy quantification on a clinical platform. In this work, we introduce a related implementation that enables simultaneous proton decoupling and ERETIC-based metabolite quantification and hence extends the applicability of the ERETIC method to nuclear Overhauser enhanced and proton decoupled in vivo (13) C magnetic resonance spectroscopy. In addition, ERETIC signal stability under the influence of simultaneous proton decoupling is investigated. The proposed quantification method was cross-validated against internal and external reference standards on human skeletal muscle. The ERETIC signal intensity stability was 100.65 +/- 4.18% over 3 months including measurements with and without proton decoupling. Glycogen and unsaturated fatty acid concentrations measured with the ERETIC method were in excellent agreement with internal creatine and external phantom reference methods, showing a difference of 1.85 +/- 1.21% for glycogen and 1.84 +/- 1.00% for unsaturated fatty acid between ERETIC and creatine-based quantification, whereas the deviations between external reference and creatine based quantification are 6.95 +/- 9.52% and 3.19 +/- 2.60%, respectively. PMID- 22084026 TI - Benzo[e]pyrene skeleton dipyrylium dication with a strong donor-acceptor-donor interaction, and its two-electron reduced molecule. AB - The donor-acceptor-donor (D-A-D) conjugated molecules 1,4 bis(diarylaminophenylethynyl)anthraquinone (1,4-Am(2)Aq) and 1,4 bis(ferrocenylethynyl)anthraquinone (1,4-Fc(2)Aq), undergo a double proton cyclization reaction with bis(trifluoromethanesulfone)imide acid (TFSIH) to yield 1,4-bis(diarylaminophenyl or ferrocenyl) dipyrylium salts [1,4 R(2)Pyl(2)](TFSI)(2) (R=Am or Fc) with novel planar pentacyclic structures similar to the aromatic benzo[e]pyrene-type skeleton. [1,4-Am(2)Pyl(2)](TFSI)(2) could be reduced to give the neutral molecule [1,4-Am(2)Pyl(2)](0), which is stable and maintains the benzo[e]pyrene-type skeleton. To the best of our knowledge, this is the first oxygen-atom-containing polycyclic aromatic hydrocarbon with 22 (4n+2) pi-electrons. The obtained condensed-ring benzo[e]pyrene-type skeleton compounds show physical and chemical properties that are significantly different from those of [1,5-Am(2)Pyl(2)](TFSI)(2), which has a perylene-type skeleton. PMID- 22084028 TI - Surgical management of T1 oropharyngeal carcinoma. AB - BACKGROUND: The purpose of this study was to assess the efficacy of primary transoral surgery in the management of T1 oropharyngeal carcinoma. METHODS: A retrospective evaluation was conducted on the files of all patients treated with primary surgery for pT1 oropharyngeal carcinoma at a tertiary referral center between 1976 and 2005. RESULTS: A total of 223 cases were assessed. Disease specific survival was 88% and local control 93%. Transoral surgery with the use of CO(2) laser or electrocautery was adopted in every case. Positive surgical margins and regional disease were found to significantly worsen prognosis. A low rate of complications and satisfactory retention of pharyngeal function were noted. CONCLUSIONS: Primary transoral surgical treatment is very effective against T1 oropharyngeal carcinoma. A low rate of complications should be expected. However, in every case complete excision of the tumor must be accomplished and the neck included in the primary treatment plan. PMID- 22084027 TI - Nitric oxide sustains long-term skeletal muscle regeneration by regulating fate of satellite cells via signaling pathways requiring Vangl2 and cyclic GMP. AB - Satellite cells are myogenic precursors that proliferate, activate, and differentiate on muscle injury to sustain the regenerative capacity of adult skeletal muscle; in this process, they self-renew through the return to quiescence of the cycling progeny. This mechanism, while efficient in physiological conditions does not prevent exhaustion of satellite cells in pathologies such as muscular dystrophy where numerous rounds of damage occur. Here, we describe a key role of nitric oxide, an important signaling molecule in adult skeletal muscle, on satellite cells maintenance, studied ex vivo on isolated myofibers and in vivo using the alpha-sarcoglycan null mouse model of dystrophy and a cardiotoxin-induced model of repetitive damage. Nitric oxide stimulated satellite cells proliferation in a pathway dependent on cGMP generation. Furthermore, it increased the number of Pax7(+)/Myf5(-) cells in a cGMP-independent pathway requiring enhanced expression of Vangl2, a member of the planar cell polarity pathway involved in the Wnt noncanonical pathway. The enhanced self-renewal ability of satellite cells induced by nitric oxide is sufficient to delay the reduction of the satellite cell pool during repetitive acute and chronic damages, favoring muscle regeneration; in the alpha-sarcoglycan null dystrophic mouse, it also slowed disease progression persistently. These results identify nitric oxide as a key messenger in satellite cells maintenance, expand the significance of the Vangl2-dependent Wnt noncanonical pathway in myogenesis, and indicate novel strategies to optimize nitric oxide-based therapies for muscular dystrophy. PMID- 22084029 TI - All organic host-guest crystals based on a dumb-bell-shaped conjugated host for light harvesting through resonant energy transfer. AB - Together we glow: Fully organic host-guest crystals with two dyes inserted in their parallel nanochannels display broad emission in the visible range thanks to resonant energy transfer. The conjugated host crystal provides light harvesting in the UV region. PMID- 22084030 TI - Energy transfer tunes phosphorescent color of single-dopant white OLEDs. PMID- 22084031 TI - Electromembrane extraction of peptides--fundamental studies on the supported liquid membrane. AB - A large screening of different components in the supported liquid membrane (SLM) in electromembrane extraction (EME) was performed to test the extraction efficiency on eight model peptides. Electromembrane extraction from a 500 MUL acidified aqueous sample containing the model peptides in the concentration 10 MUg/mL was used. Extraction time was 5 min with an electric potential of 10 V and 900 rpm agitation of the sample vial. The samples were extracted through a hollow fiber-based SLM with different compositions of organic solvents and carriers. A small volume of acidified acceptor solution (25 MUL) was after extraction analyzed directly, or with some dilution, on CE or HPLC. This article has identified mono- or di-substituted phosphate groups as the prominent group of carrier molecules needed to obtain acceptable recoveries. For the organic solvents, primary alcohols and ketones have shown promise regarding recovery and reproducibility, with some differences in selectivity. A new composition of the SLM, namely 2-octanone and tridecyl phosphate (90:10 w/w) has proved to give higher extraction recoveries and lower standard deviation than SLMs previously reported in the literature. PMID- 22084032 TI - Survey of the frequency and perceived stressfulness of ethical dilemmas encountered in UK veterinary practice. AB - The scale of the ethical challenges faced by veterinary surgeons and their perceived stressful consequences were investigated via a short questionnaire, completed by 58 practising veterinary surgeons. Respondents were asked to report how frequently they faced ethical dilemmas, and to rate on a simple numerical scale (zero to 10) how stressful they found three common scenarios. Fifty seven per cent of respondents reported that they faced one to two dilemmas per week, while 34 per cent stated they typically faced three to five dilemmas per week. The three scenarios provided were all rated as highly stressful with 'client wishing to continue treatment despite poor animal welfare' rated as the most stressful (median 9). The female veterinary surgeons gave two of the scenarios significantly higher stress ratings than the male veterinary surgeons. Stress ratings were not influenced by number of years in practice (which ranged from one to more than 25 years). The results show that veterinary surgeons regularly face ethical dilemmas and that they find these stressful. This has implications for the wellbeing of veterinary surgeons and supports the case for increased provision of training and support, especially for those who entered the profession before undergraduate ethics teaching was widely available. PMID- 22084033 TI - Human neural stem cell tropism to metastatic breast cancer. AB - Metastasis to multiple organs is the primary cause of mortality in breast cancer patients. The poor prognosis for patients with metastatic breast cancer and toxic side effects of currently available treatments necessitate the development of effective tumor-selective therapies. Neural stem cells (NSCs) possess inherent tumor tropic properties that enable them to overcome many obstacles of drug delivery that limit effective chemotherapy strategies for breast cancer. We report that increased NSC tropism to breast tumor cell lines is strongly correlated with the invasiveness of cancer cells. Interleukin 6 (IL-6) was identified as a major cytokine mediating NSC tropism to invasive breast cancer cells. We show for the first time in a preclinical mouse model of metastatic human breast cancer that NSCs preferentially target tumor metastases in multiple organs, including liver, lung, lymph nodes, and femur, versus the primary intramammary fat pad tumor. For proof-of-concept of stem cell-mediated breast cancer therapy, NSCs were genetically modified to secrete rabbit carboxylesterase (rCE), an enzyme that activates the CPT-11 prodrug to SN-38, a potent topoisomerase I inhibitor, to effect tumor-localized chemotherapy. In vitro data demonstrate that exposure of breast cancer cells to conditioned media from rCE secreting NSCs (NSC.rCE) increased their sensitivity to CPT-11 by 200-fold. In vivo, treatment of tumor-bearing mice with NSC.rCE cells in combination with CPT 11 resulted in reduction of metastatic tumor burden in lung and lymph nodes. These data suggest that NSC-mediated enzyme/prodrug therapy may be more effective and less toxic than currently available chemotherapy strategies for breast cancer metastases. PMID- 22084034 TI - Ectopic mediastinal goiter successfully managed via cervical approach: case report and review of the literature. AB - BACKGROUND: Ectopic mediastinal goiter is a rare entity that presents diagnostic and treatment challenges to the clinician. METHODS: A case of primary ectopic mediastinal goiter is presented and use of a cervical approach for excision is described herein. Additionally, precedent literature highlighting surgical treatment approaches is reviewed. RESULTS: The distinction between primary and secondary ectopic mediastinal goiter is significant as this indicates the vascular supply to the ectopic mass. Previous authors suggested open thoracic procedures for all primary mediastinal goiters to safely divide intrathoracic vascular supply, but favorably positioned anterior mediastinal goiter may be safely removed via cervical approach. This is the second case of primary ectopic mediastinal goiter successfully resected via cervical approach. CONCLUSION: Select cases of primary mediastinal goiter may be amenable to excision via cervical approach, avoiding potential complications of open thoracic procedures. Additionally, CT-guided biopsy is an effective tool in preoperative diagnosis of anterior mediastinal masses. PMID- 22084036 TI - Synthesis of tripeptide mimetics based on dihydroquinolinone and benzoxazinone scaffolds. PMID- 22084037 TI - Online tissue discrimination for transcutaneous needle guidance applications using broadband impedance spectroscopy. AB - This paper reports on a novel system architecture for measuring impedance spectra of a biological tissue close to the tip of a hollow needle. The measurement is performed online using fast broadband chirp signals. The time domain measurement raw data are transformed into the transfer function of the tissue in frequency domain. Correlation technique is used to analyze the characteristic shape of the derived tissue transfer function with respect to known "library functions" for different types of tissue derived in earlier experiments. Based on the resulting correlation coefficients the exact type of tissue is determined. A bipolar coaxial needle is constructed, simulated by finite element method and tested during various in vitro and in vivo experiments. The results show a good spatial resolution of approximately 1.0 mm for a needle with a diameter of 2.0 mm. The correlation coefficients for the three tested tissue types muscle, fat, and blood allow for a clear tissue classification. Best results have been obtained using the characteristic phase diagrams for each tissue. Correlated to the corresponding library transfer function the coefficients are in the range of +0.96 to +0.99 for the matching tissue. In return, the resulting coefficients for correlation with nonmatching tissues are in the range of -0.93 to +0.81. PMID- 22084035 TI - Simple, fast, tissue-specific bacterial artificial chromosome transgenesis in Xenopus. AB - We have developed a method of injecting bacterial artificial chromosome (BAC) DNA into Xenopus embryos that is simple and efficient, and results in consistent and tissue-specific expression of transgenes cloned into BAC vectors. Working with large pieces of DNA, as can be accommodated by BACs, is necessary when studying large or complex genes and conducive to studying the function of long-range regulatory elements that act to control developmentally restricted gene expression. We recombineered fluorescent reporters into three Xenopus tropicalis BAC clones targeting three different genes and report that up to 60% of injected embryos express the reporter in a manner consistent with endogenous expression. The behavior of these BACs, which are replicated after injection, contrasts with that of smaller plasmids, which degrade relatively quickly when injected as circular molecules and generally fail to recapitulate endogenous expression when not integrated into the Xenopus genome. PMID- 22084038 TI - Cross validation for selection of cortical interaction models from scalp EEG or MEG. AB - A cross-validation (CV) method based on state-space framework is introduced for comparing the fidelity of different cortical interaction models to the measured scalp electroencephalogram (EEG) or magnetoencephalography (MEG) data being modeled. A state equation models the cortical interaction dynamics and an observation equation represents the scalp measurement of cortical activity and noise. The measured data are partitioned into training and test sets. The training set is used to estimate model parameters and the model quality is evaluated by computing test data innovations for the estimated model. Two CV metrics normalized mean square error and log-likelihood are estimated by averaging over different training/test partitions of the data. The effectiveness of this method of model selection is illustrated by comparing two linear modeling methods and two nonlinear modeling methods on simulated EEG data derived using both known dynamic systems and measured electrocorticography data from an epilepsy patient. PMID- 22084039 TI - Setting adaptive spike detection threshold for smoothed TEO based on robust statistics theory. AB - We propose a novel approach aimed at adaptively setting the threshold of the smoothed Teager energy operator (STEO) detector to be used in extracellular recording of neural signals. In this proposed approach, to set the adaptive threshold of the STEO detector, we derive the relationship between the low-order statistics of its input signal and the ones of its output signal. This relationship is determined with only the background noise component assumed to be present at the input. Robust statistics theory techniques were used to achieve an unbiased estimation of these low-order statistics of the background noise component directly from the neural input signal. In this paper, the emphasis is made on extracellular neural recordings. However, the proposed method can be used in the analysis of different biomedical signals where spikes are important for diagnostic (e.g., ECG, EEG, etc.). We validated the efficacy of the proposed method using synthetic neural signals constructed from real neural recordings signals. Four different sets of extracellular recordings from four distinct neural sources have been exploited to that purpose. The first dataset is recorded from an adult male monkey using the Utath 10*10 microelectrode array implemented in the prefrontal cortex, the second one was obtained from the visual cortex of a rat using a stainless-steel-tipped microelectrode, the third dataset came from recording in a human medial lobe using intracranial electrode, and finally, the fourth one was extracted from recordings in a macaque parietal cortex using a single tetrode. Simulation results show that our approach is effective and robust, and outperforms state-of-the-art adaptive detection methods in its category (i.e., efficient and simple, and do not require a priori knowledge about neural spike waveforms shapes). PMID- 22084040 TI - Personalized tooth shape estimation from radiograph and cast. AB - Three-dimensional geometric information of teeth is usually needed in pre- and postoperative diagnoses of orthodontic dentistry. The computerized tomography can provide comprehensive 3-D teeth geometries. However, there is still a discussion on computed tomography (CT) as a routine in orthodontic dentistry due to radiation dose. Moreover, the CT is useless when a dentist needs to extract 3-D structures from old archive files with only radiographs and casts, where patient's teeth changed ever since. In this paper, we propose a reconstruction framework for patient-specific teeth based on an integration of 2-D radiographs and digitized casts. The reconstruction is under a template-fitting framework. The shape and orientation of teeth templates are tuned in accordance with patient's radiographs. Specially, the tooth root morphology is controlled by 2-D contours in radiographs. With ray tracing and a contour plane assumption, 2-D root contours in radiographs are projected back to 3-D space, and guide tooth root deformations. Moreover, the template's crown is deformed nonrigidly to fit digitized casts that bear patient's crown details. The system allows 3-D tooth reconstruction with patient-specific geometric details from just casts and 2-D radiographs. PMID- 22084041 TI - DiBa: a data-driven Bayesian algorithm for sleep spindle detection. AB - Although the spontaneous brain rhythms of sleep have commanded much recent interest, their detection and analysis remains suboptimal. In this paper, we develop a data-driven Bayesian algorithm for sleep spindle detection on the electroencephalography (EEG). The algorithm exploits the Karhunen-Loeve transform and Bayesian hypothesis testing to produce the instantaneous probability of a spindle's presence with maximal resolution. In addition to possessing flexibility, transparency, and scalability, this algorithm could perform at levels superior to standard methods for EEG event detection. PMID- 22084042 TI - Optimal multiresolution blending of confocal microscope images. AB - Typical mosaicing schemes assume that to-be-combined images are equally informative; thus, the images are processed in a similar manner. However, the new imaging technique for confocal fluorescence images has revealed a problem when two asymmetrically informative biological images are stitched during microscope image mosaicing. The latter process is widely used in biological studies to generate a higher resolution image by combining multiple images taken at different times and angles. To resolve the earlier problem, we propose a multiresolution optimization approach that evaluates the blending coefficients based on the relative importance of the overlapping regions of the to-be-combined image pair. The blending coefficients are the optimal solution obtained by a quadratic programming algorithm with constraints that are enforced by the biological requirements. We demonstrate the efficacy of the proposed approach on several confocal microscope fluorescence images and compare the results with those derived by other methods. PMID- 22084043 TI - Modeling the slow wave shapes of spreading depression in a rat cortex: a methodology for seeking physiological parameters. AB - Spreading depression (SD) consists of a transient significant suppression of the spontaneous neural electrical activity that spreads slowly across regions of the gray matter in a wave form. Nowadays, this phenomenon is being studied by means of mathematical and computational models to reproduce the main characteristics of SD. Given the high number of parameters and their unknown ranges of variation, the setting of parameters for current SD models is usually a hard task that must be addressed in order to make such models reproduce real data. In this paper, we present a 1-D model which is able to reproduce the most important characteristics of SD waves observed in laboratory experiments: the slow extracellular potential shift and extracellular ionic concentration variations regarding speed, shape, and amplitude. Such a reproduction is possible due to a methodology that we introduced to set the parameters of the SD models. The methodology allows the impact of each parameter on the results produced by the model and the range of parameters for which the model displays plausible behavior to be determined. The methodology also helps to identify features that the model cannot produce and it gives insights about what parts of the model should be modified to improve its capacities through the identification of parameters involved with each behavior. PMID- 22084044 TI - Vibrotactile pattern recognition: a portable compact tactile matrix. AB - Compact tactile matrix (CTM) is a vibrotactile device composed of a seven-by seven array of electromechanical vibrators "tactip" used to represent tactile patterns applied to a small skin area. The CTM uses a dynamic feature to generate spatiotemporal tactile patterns. The design requirements focus particularly on maximizing the transmission of the vibration from one tactip to the others as well as to the skin over a square area of 16 cm (2) while simultaneously minimizing the transmission of vibrations throughout the overall structure of the CTM. Experiments were conducted on 22 unpracticed subjects to evaluate how the CTM could be used to develop a tactile semantics for communication of instructions in order to test the ability of the subjects to identify: 1) directional prescriptors for gesture guidance and 2) instructional commands for operational task requirements in a military context. The results indicate that, after familiarization, recognition accuracies in the tactile patterns were remarkably precise for more 80% of the subjects. PMID- 22084046 TI - A splitting-based iterative algorithm for accelerated statistical X-ray CT reconstruction. AB - Statistical image reconstruction using penalized weighted least-squares (PWLS) criteria can improve image-quality in X-ray computed tomography (CT). However, the huge dynamic range of the statistical weights leads to a highly shift-variant inverse problem making it difficult to precondition and accelerate existing iterative algorithms that attack the statistical model directly. We propose to alleviate the problem by using a variable-splitting scheme that separates the shift-variant and ("nearly") invariant components of the statistical data model and also decouples the regularization term. This leads to an equivalent constrained problem that we tackle using the classical method-of-multipliers framework with alternating minimization. The specific form of our splitting yields an alternating direction method of multipliers (ADMM) algorithm with an inner-step involving a "nearly" shift-invariant linear system that is suitable for FFT-based preconditioning using cone-type filters. The proposed method can efficiently handle a variety of convex regularization criteria including smooth edge-preserving regularizers and nonsmooth sparsity-promoting ones based on the l(1)-norm and total variation. Numerical experiments with synthetic and real in vivo human data illustrate that cone-filter preconditioners accelerate the proposed ADMM resulting in fast convergence of ADMM compared to conventional (nonlinear conjugate gradient, ordered subsets) and state-of-the-art (MFISTA, split-Bregman) algorithms that are applicable for CT. PMID- 22084047 TI - Three-dimensional in silico breast phantoms for multimodal image simulations. AB - Anatomic simulators have provided researchers with the realistic objects needed to develop and evaluate medical imaging approaches. Today we have new insights into the cellular biology of breast tissues that is driving many new targeted diagnostic and therapeutic approaches, including molecular imaging. We report on our initial efforts to build a scalable framework for the construction of realistic 3-D in silico breast phantoms (ISBP) capable of leveraging existing knowledge and yet adaptable to fully integrate future discoveries. The ISBP frames are developed with scalable anatomical shapes and morphologic features as adapted from a rich literature on this topic. Frames are populated with tissue subtypes essential for imaging and object contrast functions are assigned. These data can be resampled to match the intrinsics scales of various imaging modalities; we explore mammography, sonography and computed tomography. Initial comparisons between simulated and clinical images demonstrate reasonable agreement and provides guidance for future development of a more realistic ISBP. An end-to-end simulation of breast images is described to demonstrate techniques for including stochastic variability and deterministic physical principles on which image formation is based. PMID- 22084048 TI - Motion correction in dual gated cardiac PET using mass-preserving image registration. AB - Respiratory and cardiac motion leads to image degradation in positron emission tomography (PET) studies of the human heart. In this paper we present a novel approach to motion correction based on dual gating and mass-preserving hyperelastic image registration. Thereby, we account for intensity modulations caused by the highly nonrigid cardiac motion. This leads to accurate and realistic motion estimates which are quantitatively validated on software phantom data and carried over to clinically relevant data using a hardware phantom. For patient data, the proposed method is first evaluated in a high statistic (20 min scans) dual gating study of 21 patients. It is shown that the proposed approach properly corrects PET images for dual-cardiac as well as respiratory-motion. In a second study the list mode data of the same patients is cropped to a scan time reasonable for clinical practice (3 min). This low statistic study not only shows the clinical applicability of our method but also demonstrates its robustness against noise obtained by hyperelastic regularization. PMID- 22084049 TI - Robust image deblurring with an inaccurate blur kernel. AB - Most existing nonblind image deblurring methods assume that the blur kernel is free of error. However, it is often unavoidable in practice that the input blur kernel is erroneous to some extent. Sometimes, the error could be severe, e.g., for images degraded by nonuniform motion blurring. When an inaccurate blur kernel is used as the input, significant distortions will appear in the image recovered by existing methods. In this paper, we present a novel convex minimization model that explicitly takes account of error in the blur kernel. The resulting minimization problem can be efficiently solved by the so-called accelerated proximal gradient method. In addition, a new boundary extension scheme is incorporated in the proposed model to further improve the results. The experiments on both synthesized and real images showed the efficiency and robustness of our algorithm to both the image noise and the model error in the blur kernel. PMID- 22084050 TI - Robust multichannel blind deconvolution via fast alternating minimization. AB - Blind deconvolution, which comprises simultaneous blur and image estimations, is a strongly ill-posed problem. It is by now well known that if multiple images of the same scene are acquired, this multichannel (MC) blind deconvolution problem is better posed and allows blur estimation directly from the degraded images. We improve the MC idea by adding robustness to noise and stability in the case of large blurs or if the blur size is vastly overestimated. We formulate blind deconvolution as an l(1) -regularized optimization problem and seek a solution by alternately optimizing with respect to the image and with respect to blurs. Each optimization step is converted to a constrained problem by variable splitting and then is addressed with an augmented Lagrangian method, which permits simple and fast implementation in the Fourier domain. The rapid convergence of the proposed method is illustrated on synthetically blurred data. Applicability is also demonstrated on the deconvolution of real photos taken by a digital camera. PMID- 22084051 TI - Selective recognition of cysteine in its free and protein-bound states by the Zn2+ complex of a triazole-based calix[4]arene conjugate. PMID- 22084052 TI - Connectivity analysis as a novel approach to motor decoding for prosthesis control. AB - The use of neural signals for prosthesis control is an emerging frontier of research to restore lost function to amputees and the paralyzed. Electrocorticography (ECoG) brain-machine interfaces (BMI) are an alternative to EEG and neural spiking and local field potential BMI approaches. Conventional ECoG BMIs rely on spectral analysis at specific electrode sites to extract signals for controlling prostheses. We compare traditional features with information about the connectivity of an ECoG electrode network. We use time varying dynamic Bayesian networks (TV-DBN) to determine connectivity between ECoG channels in humans during a motor task. We show that, on average, TV-DBN connectivity decreases from baseline preceding movement and then becomes negative, indicating an alteration in the phase relationship between electrode pairs. In some subjects, this change occurs preceding and during movement, before changes in low or high frequency power. We tested TV-DBN output in a hand kinematic decoder and obtained an average correlation coefficient (r(2)) between actual and predicted joint angle of 0.40, and as high as 0.66 in one subject. This result compares favorably with spectral feature decoders, for which the average correlation coefficient was 0.13. This work introduces a new feature set based on connectivity and demonstrates its potential to improve ECoG BMI accuracy. PMID- 22084053 TI - Aerodynamics of cyclist posture, bicycle and helmet characteristics in time trial stage. AB - The present work is focused on the aerodynamic study of different parameters, including both the posture of a cyclist's upper limbs and the saddle position, in time trial (TT) stages. The aerodynamic influence of a TT helmet large visor is also quantified as a function of the helmet inclination. Experiments conducted in a wind tunnel on nine professional cyclists provided drag force and frontal area measurements to determine the drag force coefficient. Data statistical analysis clearly shows that the hands positioning on shifters and the elbows joined together are significantly reducing the cyclist drag force. Concerning the saddle position, the drag force is shown to be significantly increased (about 3%) when the saddle is raised. The usual helmet inclination appears to be the inclination value minimizing the drag force. Moreover, the addition of a large visor on the helmet is shown to provide a drag coefficient reduction as a function of the helmet inclination. Present results indicate that variations in the TT cyclist posture, the saddle position and the helmet visor can produce a significant gain in time (up to 2.2%) during stages. PMID- 22084054 TI - Enantioselective intermolecular carbon-carbon bond formation of glyoxylate imines with allylstannanes catalyzed by tropos BIPHEP-gold(I) complexes with Au-Au interactions. PMID- 22084055 TI - Impact response and simulation of damaged ulna with internal fixation. AB - The objectives of this work were to explore a methodology that combines static and dynamic finite element (FE) analysis, linear elastic fracture mechanics (LEFM) and experimental methods to investigate a worst-case scenario in which a previously damaged bone plate system is subjected to an impact load. Cadaver ulnas with and without midshaft dynamic compression plates are subjected to a static three-point bend test and loaded such that subcritical crack growth occurs as predicted by a hybrid method that couples LEFM and static FE. The plated and unplated bones are then unloaded and subsequently subjected to a midshaft transverse impact test. A dynamic strain-based FE model is also developed to model the midshaft transverse impact test. The average value of the impact energy required for failure was observed to be 10.53% greater for the plated set. There appears to be a trade-off between impact damage and impact resistance when ulnas are supported by fixation devices. Predictions from the dynamic FE model are shown to corroborate inferences from the experimental approach. PMID- 22084057 TI - Antibacterial compounds from the mushroom Ganoderma colossum from Nigeria. AB - Three colossolactones (colossolactone E, colossolactone B and 23 hydroxycolossolactone E) were isolated and characterized from an n hexane:dichloromethane (2:7) extract of Ganoderma colossum using chromatographic techniques. The antimicrobial activity of the three compounds was then tested against Gram-positive and Gram-negative bacteria. The activity was evaluated by the thin-layer chromatography agar overlay method. The results showed that colossolactone E and 23-hydroxycolossolactone E were active against Bacillus subtilis and Pseudomonas syringae. Colossolactone B was not active against the bacteria. Their structures were elucidated by spectroscopic methods. Potency of the compounds against bacteria tested supports the use of this mushroom in therapeutic medicine. PMID- 22084058 TI - Influence of shear stress on behaviors of piezoelectric voltages in bone. AB - The piezoelectric properties of bone play an important role in the bone remodeling process and can be employed in clinical bone repair. In this study, the piezo-voltage of bone between two surfaces of a bone beam under bending deformation was measured using an ultra-high-input impedance bioamplifier. The influence of shear stress on the signs of piezo-voltages in bone was determined by comparing and contrasting the results from three-point and four-point bending experiments. From the three-point bending experiment, the study found that the signs of piezo-voltages depend only on shear stress and are not sensitive to the normal stress. PMID- 22084059 TI - An antithrombotic fucoidan, unlike heparin, does not prolong bleeding time in a murine arterial thrombosis model: a comparative study of Undaria pinnatifida sporophylls and Fucus vesiculosus. AB - The antithrombotic activities and bleeding effects of selected fucoidans (source from either Undaria pinnatifida sporophylls or from Fucus vesiculosus) have been compared with heparin in the ferric chloride-induced arterial thrombus mouse model. Thrombosis was induced by applying 5% ferric chloride for 3 min on the carotid artery region of Balb/c mouse. Five minutes prior to thrombus induction, mice were infused through the tail vein with either saline (control) or polysaccharides. Either fucoidan or heparin was dosed at 0.1, 1.25, 2.5, 5.0, 10, 25, or 50 mg/kg intravenously (i.v.) The carotid blood flow was monitored until more than 60 min post-thrombus induction. Mouse tail transection bleeding time was measured up to 60 min after making a cut in the mouse tail. Both antithrombotic and bleeding effects were observed in a dose-dependent manner for both fucoidans and heparin. Thrombus formation was totally (reflected by Doppler flow meter) inhibited at either 5 or 50 mg/kg of unfractionated Undaria fucoidan or a low-molecular-weight Undaria fucoidan fraction, respectively, without prolonging the time-to-stop bleeding compared with the control (p < 0.01). The total inhibition of thrombus formation was observed for unfractionated Fucus fucoidan at 25 mg/kg where the time-to-stop bleeding was still significantly prolonged, by as much as 8 +/- 1.7 min (p < 0.02). In contrast the heparin treated group showed total inhibition of thrombus formation even at a small dose of 0.8 mg/kg (400 IU) at which bleeding continued until 60 min. In conclusion algal fucoidans are highly antithrombotic without potential haemorrhagic effects compared with heparin in the arterial thrombus model, but this property differs from algal species to species, and from the molecular structure of fucoidans. PMID- 22084060 TI - The antimutagenic effect of mistletoe lectin (Viscum album L. var. coloratum agglutinin). AB - A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. var. coloratum agglutinin, VCA), which is known for its anticancer activity, was isolated from mistletoe. In this study, we investigated the antimutagenic potentials of VCA by using the pre-incubation method of the Ames test (Salmonella typhimurium TA98 and TA100) in the presence or absence of S9 mixture. Viscum album L. var. coloratum agglutinin was assessed for its antimutagenic properties against the mutagens 2-aminoanthracene (2AA) and furylfuramide (AF-2) for strain TA98, and sodium azide (NaN(3) ) and 2-aminoanthracene (2AA) for strain TA100. The concentrations used for this test compound were 100, 200 and 400 ug per plate. Viscum album L. var. coloratum agglutinin showed moderate, but not negligible, protective effects regarding the antimutagenic properties against the direct-acting mutagens NaN(3) and AF-2. Furthermore, VCA was more effective in preventing the mutagenicity of the indirect-acting mutagen 2-AA (in the presence of S9) when tested with both TA98 and TA100. In conclusion, this report has shown broad ranging antimutagenic effects of VCA to numerous mutagens in TA98 and TA100 Salmonella typhimurium strains. Although the data presented here cannot be applied in vivo, they can support other antimutagenic and anticarcinogenic findings for VCA. PMID- 22084061 TI - Red clover extract ameliorates dyslipidemia in streptozotocin-induced diabetic C57BL/6 mice by activating hepatic PPARalpha. AB - The effects of red clover extract and its bioactive components, biochanin A and formononetin, on the blood glucose and lipid levels of streptozotocin (STZ) induced-diabetic mice were investigated. Male diabetic C57BL/6 mice were induced by multiple low-dose STZ administration and then treated with red clover extract or isoflavones for a period of 3 weeks. Red clover extract had no significant effect on lowering the blood glucose levels of STZ-diabetic mice. Similarly, biochanin A and formononetin exerted no hypoglycemic effect. However, the serum triglycerides, total cholesterols and low-density lipoprotein-cholesterol levels for STZ-diabetic mice receiving red clover extract were significantly lower than that of untreated STZ-diabetic mice. In addition, treatment with biochanin A or formononetin significantly ameliorated these lipid profiles in diabetic mice. The mRNA expression of two target genes transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR) alpha were determined by semi-quantitative RT-PCR and biochanin A or formononetin were found to significantly down-regulate hepatic APOC3 expression, whereas they had no significant effect on hepatic APOA5 expression. Thus we conclude that red clover extract and biochanin A or formononetin significantly ameliorate the lipid profiles of STZ-diabetic mice and these effects are achieved at least in part by activating hepatic PPARalpha. PMID- 22084063 TI - Direct-bandgap light-emitting germanium in tensilely strained nanomembranes. AB - Silicon, germanium, and related alloys, which provide the leading materials platform of electronics, are extremely inefficient light emitters because of the indirect nature of their fundamental energy bandgap. This basic materials property has so far hindered the development of group-IV photonic active devices, including diode lasers, thereby significantly limiting our ability to integrate electronic and photonic functionalities at the chip level. Here we show that Ge nanomembranes (i.e., single-crystal sheets no more than a few tens of nanometers thick) can be used to overcome this materials limitation. Theoretical studies have predicted that tensile strain in Ge lowers the direct energy bandgap relative to the indirect one. We demonstrate that mechanically stressed nanomembranes allow for the introduction of sufficient biaxial tensile strain to transform Ge into a direct-bandgap material with strongly enhanced light-emission efficiency, capable of supporting population inversion as required for providing optical gain. PMID- 22084062 TI - Frozen steady states in active systems. AB - Even simple active systems can show a plethora of intriguing phenomena and often we find complexity where we would have expected simplicity. One striking example is the occurrence of a quiescent or absorbing state with frozen fluctuations that at first sight seems to be impossible for active matter driven by the incessant input of energy. While such states were reported for externally driven systems through macroscopic shear or agitation, the investigation of frozen active states in inherently active systems like cytoskeletal suspensions or active gels is still at large. Using high-density motility assay experiments, we demonstrate that frozen steady states can arise in active systems if active transport is coupled to growth processes. The experiments are complemented by agent-based simulations which identify the coupling between self-organization, growth, and mechanical properties to be responsible for the pattern formation process. PMID- 22084064 TI - Nitrosyl hydride (HNO) replaces dioxygen in nitroxygenase activity of manganese quercetin dioxygenase. AB - Quercetin dioxygenase (QDO) catalyzes the oxidation of the flavonol quercetin with dioxygen, cleaving the central heterocyclic ring and releasing CO. The QDO from Bacillus subtilis is unusual in that it has been shown to be active with several divalent metal cofactors such as Fe, Mn, and Co. Previous comparison of the catalytic activities suggest that Mn(II) is the preferred cofactor for this enzyme. We herein report the unprecedented substitution of nitrosyl hydride (HNO) for dioxygen in the activity of Mn-QDO, resulting in the incorporation of both N and O atoms into the product. Turnover is demonstrated by consumption of quercetin and other related substrates under anaerobic conditions in the presence of HNO-releasing compounds and the enzyme. As with dioxygenase activity, a nonenzymatic base-catalyzed reaction of quercetin with HNO is observed above pH 7, but no enhancement of this basal reactivity is found upon addition of divalent metal salts. Unique and regioselective N-containing products ((14)N/(15)N) have been characterized by MS analysis for both the enzymatic and nonenzymatic reactions. Of the several metallo-QDO enzymes examined for nitroxygenase activity under anaerobic condition, only the Mn(II) is active; the Fe(II) and Co(II) substituted enzymes show little or no activity. This result represents an enzymatic catalysis which we denote nitroxygenase activity; the unique reactivity of the Mn-QDO suggests a metal-mediated electron transfer mechanism rather than metal activation of the substrate's inherent base-catalyzed reactivity. PMID- 22084065 TI - Imaging guided trials of the angiogenesis inhibitor sunitinib in mouse models predict efficacy in pancreatic neuroendocrine but not ductal carcinoma. AB - Preclinical trials in mice represent a critical step in the evaluation of experimental therapeutics. Genetically engineered mouse models (GEMMs) represent a promising platform for the evaluation of drugs, particularly those targeting the tumor microenvironment. We evaluated sunitinib, an angiogenesis inhibitor that targets VEGF and PDGF receptor signaling, in two GEMMs of pancreatic cancer. Sunitinib did not reduce tumor burden in pancreatic ductal adenocarcinoma (PDAC), whereas tumor burden was reduced in the pancreatic neuroendocrine tumor (PNET) model, the latter results confirming and extending previous studies. To explore the basis for the lack of pathologic response in PDAC, we used noninvasive microbubble contrast-enhanced ultrasound imaging, which revealed that sunitinib reduced blood flow both in PDAC and in PNET, concomitant with a reduction in vessel density; nevertheless, PDAC tumors continued to grow, whereas PNET were growth impaired. These results parallel the response in humans, where sunitinib recently garnered FDA and European approval in PNET, whereas two antiangiogenic drugs failed to demonstrate efficacy in PDAC clinical trials. The demonstration of on-target activity but with discordant benefit in the PDAC and PNET GEMMs illustrates the potential value of linked preclinical and clinical trials. PMID- 22084066 TI - Differential effects on p53-mediated cell cycle arrest vs. apoptosis by p90. AB - p53 functions as a central node for organizing whether the cell responds to stress with apoptosis or cell cycle arrest; however, the molecular events that lead to apoptotic responses are not completely understood. Here, we identified p90 (also called Coiled-Coil Domain Containing 8) as a unique regulator for p53. p90 has no obvious effects on either the levels of p53 or p53-mediated cell cycle arrest but is specifically required for p53-mediated apoptosis upon DNA damage. Notably, p90 is crucial for Tip60-dependent p53 acetylation at Lys120, therefore facilitating activation of the proapoptotic targets. These studies indicate that p90 is a critical cofactor for p53-mediated apoptosis through promoting Tip60 mediated p53 acetylation. PMID- 22084067 TI - Organ aging and susceptibility to cancer may be related to the geometry of the stem cell niche. AB - Telomere loss at each cell replication limits the proliferative capacity of normal cells, including adult stem cells. Entering replicative senescence protects dividing cells from neoplastic transformation, but also contributes to aging of the tissue. Recent experiments have shown that intestinal mouse stem cells divide symmetrically, at random make decisions to remain stem cells or to differentiate, and gradually lose telomeric DNA. A cell's decision whether to differentiate or to remain a stem cell depends on the local cellular and chemical environment and thus tissue architecture is expected to play role in cell proliferation dynamics. To take into account the structure of the stem cell niche in determining its proliferative potential and susceptibility to cancer, a theoretical model is introduced and the niche proliferative potential is quantified for different architectures. The niche proliferative potential is quantitatively related to the proliferative potential of the individual stem cells for different structural classes of the stem cell niche. Stem cells at the periphery of a niche are under pressure to divide and to differentiate, as well as to maintain the stem cell niche boundary, and thus the geometry of the stem cell niche is expected to play a role in determining the stem cell division sequence and differentiation. Smaller surface-to-volume ratio is associated with higher susceptibility to cancer, higher tissue renewal capacity, and decreased aging rate. Several testable experimental predictions are discussed, as well the presence of stochastic effects. PMID- 22084068 TI - Landslide-dammed paleolake perturbs marine sedimentation and drives genetic change in anadromous fish. AB - Large bedrock landslides have been shown to modulate rates and processes of river activity by forming dams, forcing upstream aggradation of water and sediment, and generating catastrophic outburst floods. Less apparent is the effect of large landslide dams on river ecosystems and marine sedimentation. Combining analyses of 1-m resolution topographic data (acquired via airborne laser mapping) and field investigation, we present evidence for a large, landslide-dammed paleolake along the Eel River, CA. The landslide mass initiated from a high-relief, resistant outcrop which failed catastrophically, blocking the Eel River with an approximately 130-m-tall dam. Support for the resulting 55-km-long, 1.3-km(3) lake includes subtle shorelines cut into bounding terrain, deltas, and lacustrine sediments radiocarbon dated to 22.5 ka. The landslide provides an explanation for the recent genetic divergence of local anadromous (ocean-run) steelhead trout (Oncorhynchus mykiss) by blocking their migration route and causing gene flow between summer run and winter run reproductive ecotypes. Further, the dam arrested the prodigious flux of sediment down the Eel River; this cessation is recorded in marine sedimentary deposits as a 10-fold reduction in deposition rates of Eel-derived sediment and constitutes a rare example of a terrestrial event transmitted through the dispersal system and recorded offshore. PMID- 22084069 TI - Low absorption losses of strongly coupled surface plasmons in nanoparticle assemblies. AB - Coupled surface plasmons in one-dimensional assemblies of metal nanoparticles have attracted significant attention because strong interparticle interactions lead to large electromagnetic field enhancements that can be exploited for localizing and amplifying electromagnetic radiation in nanoscale structures. Ohmic loss (i.e., absorption by the metal), however, limits the performance of any application due to nonradiative surface plasmon relaxation. While absorption losses have been studied theoretically, they have not been quantified experimentally for strongly coupled surface plasmons. Here, we report on the ohmic loss in one-dimensional assemblies of gold nanoparticles with small interparticle separations of only a few nanometers and hence strong plasmon coupling. Both the absorption and scattering cross-sections of coupled surface plasmons were determined and compared to electrodynamic simulations. A lower absorption and higher scattering cross-section for coupled surface plasmons compared to surface plasmons of isolated nanoparticles suggest that coupled surface plasmons suffer smaller ohmic losses and therefore act as better antennas. These experimental results provide important insight for the design of plasmonic devices. PMID- 22084070 TI - Assessment of individual radionuclide distributions from the Fukushima nuclear accident covering central-east Japan. AB - A tremendous amount of radioactivity was discharged because of the damage to cooling systems of nuclear reactors in the Fukushima No. 1 nuclear power plant in March 2011. Fukushima and its adjacent prefectures were contaminated with fission products from the accident. Here, we show a geographical distribution of radioactive iodine, tellurium, and cesium in the surface soils of central-east Japan as determined by gamma-ray spectrometry. Especially in Fukushima prefecture, contaminated area spreads around Iitate and Naka-Dori for all the radionuclides we measured. Distributions of the radionuclides were affected by the physical state of each nuclide as well as geographical features. Considering meteorological conditions, it is concluded that the radioactive material transported on March 15 was the major contributor to contamination in Fukushima prefecture, whereas the radioactive material transported on March 21 was the major source in Ibaraki, Tochigi, Saitama, and Chiba prefectures and in Tokyo. PMID- 22084071 TI - Evolutionary dynamics of feedback escape and the development of stem-cell-driven cancers. AB - Cancers are thought to arise in tissue stem cells, and similar to healthy tissue, are thought to be maintained by a small population of tumor stem or initiating cells, whereas the majority of tumor cells are more differentiated with limited replicative potential. Healthy tissue homeostasis is achieved by feedback loops, and particular importance has been attached to signals secreted from differentiated cells that inhibit stem-cell division and stem-cell self-renewal, as documented in the olfactory epithelium and other tissues. Therefore, a key event in carcinogenesis must be escape from these feedback loops, which is studied here using evolutionary computational models. We find that out of all potential evolutionary pathways, only one unique sequence of phenotypic transitions can lead to complete escape in stem-cell-driven tumors, even though the required mutations for these transitions are certainly tissue specific. This insight, supported by data, facilitates the search for driver mutations and for therapeutic targets. Different growth patterns can result from feedback escape, which we call "inhibited," "uninhibited," and "sigmoidal," and which are found in published data. The finding of inhibited growth patterns in data indicates that besides architecture, the regulatory mechanisms of healthy tissue continue to operate to a degree in tumors. PMID- 22084072 TI - Evidence for an allosteric mechanism of substrate release from membrane transporter accessory binding proteins. AB - Numerous membrane importers rely on accessory water-soluble proteins to capture their substrates. These substrate-binding proteins (SBP) have a strong affinity for their ligands; yet, substrate release onto the low-affinity membrane transporter must occur for uptake to proceed. It is generally accepted that release is facilitated by the association of SBP and transporter, upon which the SBP adopts a conformation similar to the unliganded state, whose affinity is sufficiently reduced. Despite the appeal of this mechanism, however, direct supporting evidence is lacking. Here, we use experimental and theoretical methods to demonstrate that an allosteric mechanism of enhanced substrate release is indeed plausible. First, we report the atomic-resolution structure of apo TeaA, the SBP of the Na(+)-coupled ectoine TRAP transporter TeaBC from Halomonas elongata DSM2581(T), and compare it with the substrate-bound structure previously reported. Conformational free-energy landscape calculations based upon molecular dynamics simulations are then used to dissect the mechanism that couples ectoine binding to structural change in TeaA. These insights allow us to design a triple mutation that biases TeaA toward apo-like conformations without directly perturbing the binding cleft, thus mimicking the influence of the membrane transporter. Calorimetric measurements demonstrate that the ectoine affinity of the conformationally biased triple mutant is 100-fold weaker than that of the wild type. By contrast, a control mutant predicted to be conformationally unbiased displays wild-type affinity. This work thus demonstrates that substrate release from SBPs onto their membrane transporters can be facilitated by the latter through a mechanism of allosteric modulation of the former. PMID- 22084073 TI - Friction mechanism of individual multilayered nanoparticles. AB - Inorganic nanoparticles of layered [two-dimensional (2D)] compounds with hollow polyhedral structure, known as fullerene-like nanoparticles (IF), were found to have excellent lubricating properties. This behavior can be explained by superposition of three main mechanisms: rolling, sliding, and exfoliation material transfer (third body). In order to elucidate the tribological mechanism of individual nanoparticles in different regimes, in situ axial nanocompression and shearing forces were applied to individual nanoparticles using a high resolution scanning electron microscope. Gold nanoparticles deposited onto the IF nanoparticles surface served as markers, delineating the motion of individual IF nanoparticle. It can be concluded from these experiments that rolling is an important lubrication mechanism for IF-WS(2) in the relatively low range of normal stress (0.96 +/- 0.38 GPa). Sliding is shown to be relevant under slightly higher normal stress, where the spacing between the two mating surfaces does not permit free rolling of the nanoparticles. Exfoliation of the IF nanoparticles becomes the dominant mechanism at the high end of normal stress; above 1.2 GPa and (slow) shear; i.e., boundary lubrication conditions. It is argued that the modus operandi of the nanoparticles depends on their degree of crystallinity (defects); sizes; shape, and their mechanical characteristics. This study suggests that the rolling mechanism, which leads to low friction and wear, could be attained by improving the sphericity of the IF nanoparticle, the dispersion (deagglomeration) of the nanoparticles, and the smoothness of the mating surfaces. PMID- 22084074 TI - Cesium-137 deposition and contamination of Japanese soils due to the Fukushima nuclear accident. AB - The largest concern on the cesium-137 ((137)Cs) deposition and its soil contamination due to the emission from the Fukushima Daiichi Nuclear Power Plant (NPP) showed up after a massive quake on March 11, 2011. Cesium-137 ((137)Cs) with a half-life of 30.1 y causes the largest concerns because of its deleterious effect on agriculture and stock farming, and, thus, human life for decades. Removal of (137)Cs contaminated soils or land use limitations in areas where removal is not possible is, therefore, an urgent issue. A challenge lies in the fact that estimates of (137)Cs emissions from the Fukushima NPP are extremely uncertain, therefore, the distribution of (137)Cs in the environment is poorly constrained. Here, we estimate total (137)Cs deposition by integrating daily observations of (137)Cs deposition in each prefecture in Japan with relative deposition distribution patterns from a Lagrangian particle dispersion model, FLEXPART. We show that (137)Cs strongly contaminated the soils in large areas of eastern and northeastern Japan, whereas western Japan was sheltered by mountain ranges. The soils around Fukushima NPP and neighboring prefectures have been extensively contaminated with depositions of more than 100,000 and 10,000 MBq km( 2), respectively. Total (137)Cs depositions over two domains: (i) the Japan Islands and the surrounding ocean (130-150 degrees E and 30-46 degrees N) and, (ii) the Japan Islands, were estimated to be approximately 6.7 and 1.3 PBq, [corrected] respectively.We hope our (137)Cs deposition maps will help to coordinate decontamination efforts and plan regulatory measures in Japan. PMID- 22084075 TI - An entirely specific type I A-kinase anchoring protein that can sequester two molecules of protein kinase A at mitochondria. AB - A-kinase anchoring proteins (AKAPs) tether the cAMP-dependent protein kinase (PKA) to intracellular sites where they preferentially phosphorylate target substrates. Most AKAPs exhibit nanomolar affinity for the regulatory (RII) subunit of the type II PKA holoenzyme, whereas dual-specificity anchoring proteins also bind the type I (RI) regulatory subunit of PKA with 10-100-fold lower affinity. A range of cellular, biochemical, biophysical, and genetic approaches comprehensively establish that sphingosine kinase interacting protein (SKIP) is a truly type I-specific AKAP. Mapping studies located anchoring sites between residues 925-949 and 1,140-1,175 of SKIP that bind RI with dissociation constants of 73 and 774 nM, respectively. Molecular modeling and site-directed mutagenesis approaches identify Phe 929 and Tyr 1,151 as RI-selective binding determinants in each anchoring site. SKIP complexes exist in different states of RI-occupancy as single-molecule pull-down photobleaching experiments show that 41 +/- 10% of SKIP sequesters two YFP-RI dimers, whereas 59 +/- 10% of the anchoring protein binds a single YFP-RI dimer. Imaging, proteomic analysis, and subcellular fractionation experiments reveal that SKIP is enriched at the inner mitochondrial membrane where it associates with a prominent PKA substrate, the coiled-coil helix protein ChChd3. PMID- 22084076 TI - Mechanical stochastic tug-of-war models cannot explain bidirectional lipid droplet transport. AB - Intracellular transport via the microtubule motors kinesin and dynein plays an important role in maintaining cell structure and function. Often, multiple kinesin or dynein motors move the same cargo. Their collective function depends critically on the single motors' detachment kinetics under load, which we experimentally measure here. This experimental constraint--combined with other experimentally determined parameters--is then incorporated into theoretical stochastic and mean-field models. Comparison of modeling results and in vitro data shows good agreement for the stochastic, but not mean-field, model. Many cargos in vivo move bidirectionally, frequently reversing course. Because both kinesin and dynein are present on the cargos, one popular hypothesis explaining the frequent reversals is that the opposite-polarity motors engage in unregulated stochastic tugs-of-war. Then, the cargos' motion can be explained entirely by the outcome of these opposite-motor competitions. Here, we use fully calibrated stochastic and mean-field models to test the tug-of-war hypothesis. Neither model agrees well with our in vivo data, suggesting that, in addition to inevitable tugs-of-war between opposite motors, there is an additional level of regulation not included in the models. PMID- 22084077 TI - Socially transmitted gut microbiota protect bumble bees against an intestinal parasite. AB - Populations of important pollinators, such as bumble bees and honey bees, are declining at alarming rates worldwide. Parasites are likely contributing to this phenomenon. A distinct resident community of bacteria has recently been identified in bumble bees and honey bees that is not shared with related solitary bee species. We now show that the presence of these microbiota protects bee hosts against a widespread and highly virulent natural parasite (Crithidia bombi) in an experimental setting. We add further support to this antagonistic relationship from patterns found in field data. For the successful establishment of these microbiota and a protective effect, exposure to feces from nest mates was needed after pupal eclosion. Transmission of beneficial gut bacteria could therefore represent an important benefit of sociality. Our results stress the importance of considering the host microbiota as an "extended immune phenotype" in addition to the host immune system itself and provide a unique perspective to understanding bees in health and disease. PMID- 22084079 TI - Two processes support visual recognition memory in rhesus monkeys. AB - A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans. PMID- 22084078 TI - Basic residues in the T-cell receptor zeta cytoplasmic domain mediate membrane association and modulate signaling. AB - The T-cell receptor (TCR) consists of a TCRalphabeta heterodimer, a TCRzeta homodimer, and CD3gammaepsilon and CD3deltaepsilon heterodimers. The precise mechanism of T-cell triggering following TCR ligand engagement remains elusive. Previous studies reported that the cytoplasmic tail of CD3epsilon binds to the plasma membrane through a basic residue-rich stretch (BRS) and proposed that dissociation from the membrane is required for phosphorylation thereof. In this report we show that BRS motifs within the cytoplasmic tail of TCRzeta mediate association with the plasma membrane and that TCR engagement results in TCRzeta dissociation from the membrane. This dissociation requires phosphorylation of the TCRzeta immunoreceptor tyrosine-based activation motifs by lymphocyte cell specificprotein tyrosine kinase (Lck) but not zeta-chain-associated protein kinase 70 binding. Mutations of the TCRzeta BRS motifs that disrupt this membrane association attenuate proximal and distal responses induced by TCR engagement. These mutations appear to alter the localization of TCRzeta with respect to Lck as well as the mobility of the TCR complex. This study reveals that tyrosine phosphorylation of the TCRzeta cytoplasmic domain regulates its association with the plasma membrane and highlights the functional importance of TCRzeta BRS motifs. PMID- 22084080 TI - On the strengths and drawbacks of tsunami-buffer forests. PMID- 22084081 TI - Social network models predict movement and connectivity in ecological landscapes. AB - Network analysis is on the rise across scientific disciplines because of its ability to reveal complex, and often emergent, patterns and dynamics. Nonetheless, a growing concern in network analysis is the use of limited data for constructing networks. This concern is strikingly relevant to ecology and conservation biology, where network analysis is used to infer connectivity across landscapes. In this context, movement among patches is the crucial parameter for interpreting connectivity but because of the difficulty of collecting reliable movement data, most network analysis proceeds with only indirect information on movement across landscapes rather than using observed movement to construct networks. Statistical models developed for social networks provide promising alternatives for landscape network construction because they can leverage limited movement information to predict linkages. Using two mark-recapture datasets on individual movement and connectivity across landscapes, we test whether commonly used network constructions for interpreting connectivity can predict actual linkages and network structure, and we contrast these approaches to social network models. We find that currently applied network constructions for assessing connectivity consistently, and substantially, overpredict actual connectivity, resulting in considerable overestimation of metapopulation lifetime. Furthermore, social network models provide accurate predictions of network structure, and can do so with remarkably limited data on movement. Social network models offer a flexible and powerful way for not only understanding the factors influencing connectivity but also for providing more reliable estimates of connectivity and metapopulation persistence in the face of limited data. PMID- 22084082 TI - Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care. AB - Neuropeptide Y (NPY) plays an important role in stress, anxiety, obesity, and energy homeostasis via activation of NPY-Y1 receptors (Y1Rs) in the brain. However, global knockout of the Npy1r gene has low or no impact on anxiety and body weight. To uncover the role of limbic Y1Rs, we generated conditional knockout mice in which the inactivation of the Npy1r gene was restricted to excitatory neurons of the forebrain, starting from juvenile stages (Npy1r(rfb)). Npy1r(rfb) mice exhibited increased anxiety and reduced body weight, less adipose tissue, and lower serum leptin levels. Npy1r(rfb) mutants also had a hyperactive hypothalamic-pituitary-adrenocortical axis, as indicated by higher peripheral corticosterone and higher density of NPY immunoreactive fibers and corticotropin releasing hormone immunoreactive cell bodies in the paraventricular hypothalamic nucleus. Importantly, through fostering experiments, we determined that differences in phenotype between Npy1r(rfb) and Npy1r(2lox) mice became apparent when both genotypes were raised by FVB/J but not by C57BL/6J dams, suggesting that limbic Y1Rs are key targets of maternal care-induced programming of anxiety and energy homeostasis. PMID- 22084083 TI - Conformational lability in the class II MHC 310 helix and adjacent extended strand dictate HLA-DM susceptibility and peptide exchange. AB - HLA-DM is required for efficient peptide exchange on class II MHC molecules, but its mechanism of action is controversial. We trapped an intermediate state of class II MHC HLA-DR1 by substitution of alphaF54, resulting in a protein with increased HLA-DM binding affinity, weakened MHC-peptide hydrogen bonding as measured by hydrogen-deuterium exchange mass spectrometry, and increased susceptibility to DM-mediated peptide exchange. Structural analysis revealed a set of concerted conformational alterations at the N-terminal end of the peptide binding site. These results suggest that interaction with HLA-DM is driven by a conformational change of the MHC II protein in the region of the alpha-subunit 3(10) helix and adjacent extended strand region, and provide a model for the mechanism of DM-mediated peptide exchange. PMID- 22084084 TI - Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation. AB - Pancreatic beta-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing beta-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of beta-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in beta-cell differentiation in the zebrafish, including down regulation of GTP production and retinoic acid biosynthesis. PMID- 22084085 TI - Nonlinear response of summer temperature to Holocene insolation forcing in Alaska. AB - Regional climate responses to large-scale forcings, such as precessional changes in solar irradiation and increases in anthropogenic greenhouse gases, may be nonlinear as a result of complex interactions among earth system components. Such nonlinear behaviors constitute a major source of climate "surprises" with important socioeconomic and ecological implications. Paleorecords are key for elucidating patterns and mechanisms of nonlinear responses to radiative forcing, but their utility has been greatly limited by the paucity of quantitative temperature reconstructions. Here we present Holocene July temperature reconstructions on the basis of midge analysis of sediment cores from three Alaskan lakes. Results show that summer temperatures during 10,000-5,500 calibrated years (cal) B.P. were generally lower than modern and that peak summer temperatures around 5,000 were followed by a decreasing trend toward the present. These patterns stand in stark contrast with the trend of precessional insolation, which decreased by ~10% from 10,000 y ago to the present. Cool summers before 5,500 cal B.P. coincided with extensive summer ice cover in the western Arctic Ocean, persistence of a positive phase of the Arctic Oscillation, predominantly La Nina-like conditions, and variation in the position of the Alaskan treeline. These results illustrate nonlinear responses of summer temperatures to Holocene insolation radiative forcing in the Alaskan sub-Arctic, possibly because of state changes in the Arctic Oscillation and El Nino-Southern Oscillation and associated land-atmosphere-ocean feedbacks. PMID- 22084086 TI - Transcriptomic resilience to global warming in the seagrass Zostera marina, a marine foundation species. AB - Large-scale transcription profiling via direct cDNA sequencing provides important insights as to how foundation species cope with increasing climatic extremes predicted under global warming. Species distributed along a thermal cline, such as the ecologically important seagrass Zostera marina, provide an opportunity to assess temperature effects on gene expression as a function of their long-term adaptation to heat stress. We exposed a southern and northern European population of Zostera marina from contrasting thermal environments to a realistic heat wave in a common-stress garden. In a fully crossed experiment, eight cDNA libraries, each comprising ~125 000 reads, were obtained during and after a simulated heat wave, along with nonstressed control treatments. Although gene-expression patterns during stress were similar in both populations and were dominated by classical heat-shock proteins, transcription profiles diverged after the heat wave. Gene-expression patterns in southern genotypes returned to control values immediately, but genotypes from the northern site failed to recover and revealed the induction of genes involved in protein degradation, indicating failed metabolic compensation to high sea-surface temperature. We conclude that the return of gene-expression patterns during recovery provides critical information on thermal adaptation in aquatic habitats under climatic stress. As a unifying concept for ecological genomics, we propose transcriptomic resilience, analogous to ecological resilience, as an important measure to predict the tolerance of individuals and hence the fate of local populations in the face of global warming. PMID- 22084088 TI - First synchronous retreat of ice shelves marks a new phase of polar deglaciation. PMID- 22084087 TI - Increase in dNTP pool size during the DNA damage response plays a key role in spontaneous and induced-mutagenesis in Escherichia coli. AB - Exposure of Escherichia coli to UV light increases expression of NrdAB, the major ribonucleotide reductase leading to a moderate increase in dNTP levels. The role of elevated dNTP levels during translesion synthesis (TLS) across specific replication-blocking lesions was investigated. Here we show that although the specialized DNA polymerase PolV is necessary for replication across UV-lesions, such as cyclobutane pyrimidine dimers or pyrimidine(6-4)pyrimidone photoproduct, Pol V per se is not sufficient. Indeed, efficient TLS additionally requires elevated dNTP levels. Similarly, for the bypass of an N-2-acetylaminofluorene guanine adduct that requires Pol II instead of PolV, efficient TLS is only observed under conditions of high dNTP levels. We suggest that increased dNTP levels transiently modify the activity balance of Pol III (i.e., increasing the polymerase and reducing the proofreading functions). Indeed, we show that the stimulation of TLS by elevated dNTP levels can be mimicked by genetic inactivation of the proofreading function (mutD5 allele). We also show that spontaneous mutagenesis increases proportionally to dNTP pool levels, thus defining a unique spontaneous mutator phenotype. The so-called "dNTP mutator" phenotype does not depend upon any of the specialized DNA polymerases, and is thus likely to reflect an increase in Pol III's own replication errors because of the modified activity balance of Pol III. As up-regulation of the dNTP pool size represents a common physiological response to DNA damage, the present model is likely to represent a general and unique paradigm for TLS pathways in many organisms. PMID- 22084089 TI - Metacommunity theory explains the emergence of food web complexity. AB - Food webs are highly complex ecological networks, dynamic in both space and time. Metacommunity models are now at the core of unified theories of biodiversity, but to date they have not addressed food web complexity. Here we show that metacommunity theory can explain the emergence of species-rich food webs with complex network topologies. Our analysis shows that network branching in the food web is maximized at intermediate colonization rates and limited dispersal scales, which also leads to concomitant peaks in species diversity. Increased food web complexity and species diversity are made possible by the structural role played by network branches that are supported by omnivore and generalist feeding links. Thus, in contrast to traditional food web theory, which emphasizes the destabilizing effect of omnivory feeding in closed systems, metacommunity theory predicts that these feeding links, which are commonly observed in empirical food webs, play a critical structural role as food webs assemble in space. As this mechanism functions at the metacommunity level, evidence for its operation in nature will be obtained through multiscale surveys of food web structure. Finally, we apply our theory to reveal the effects of habitat destruction on network complexity and metacommunity diversity. PMID- 22084090 TI - Statistical learning of visual transitions in monkey inferotemporal cortex. AB - One of the most fundamental functions of the brain is to predict upcoming events on the basis of the recent past. A closely related function is to signal when a prediction has been violated. The identity of the brain regions that mediate these functions is not known. We set out to determine whether they are implemented at the level of single neurons in the visual system. We gave monkeys prolonged exposure to pairs of images presented in fixed sequence so that each leading image became a strong predictor for the corresponding trailing image. We then monitored the responses of neurons in the inferotemporal cortex to image sequences that obeyed or violated the transitional rules imposed during training. Inferotemporal neurons exhibited a transitional surprise effect, responding much more strongly to unpredicted transitions than to predicted transitions. Thus, neurons even in the visual system make experience-based predictions and react when they fail. PMID- 22084091 TI - Cell cycle adaptations of embryonic stem cells. AB - ES cells proliferate with very short gap phases yet maintain their capacity to differentiate. It had been thought that the levels of cyclins and other substrates of ubiquitin ligase APC/C remain nearly constant and Cdk activity remains constitutively high in mouse ES cells. Here we demonstrate that APC/C (anaphase-promoting complex/cyclosome) enzyme is active in ES cells but attenuated by high levels of the Emi1 (early mitotic inhibitor-1) protein. Despite the presence of high Cdk activity during the G1 phase, chromatin can be effectively licensed for DNA replication and fast entry into the S phase can still occur. High Cdk activity during S-G2-M phases produces high levels of the DNA replication factor Cdt1, and this leads to efficient Mcm proteins loading on chromatin after mitotic exit. Although disturbing the usual balance between Cdk activity and APC/C activity found in somatic cells, a few key adaptations allow normal progression of a very rapid cell cycle. PMID- 22084092 TI - Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing. AB - Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG) 1 activates class I ADP ribosylation factors (ARFs) by accelerating the replacement of bound GDP with GTP to initiate recruitment of coat proteins for membrane vesicle formation. Among proteins that interact with BIG1, kinesin family member 21A (KIF21A), a plus-end-directed motor protein, moves cargo away from the microtubule-organizing center (MTOC) on microtubules. Because KANK1, a protein containing N-terminal KN, C-terminal ankyrin-repeat, and intervening coiled-coil domains, has multiple actions in cells and also interacts with KIF21A, we explored a possible interaction between it and BIG1. We obtained evidence for a functional and physical association between these proteins, and found that the effects of BIG1 and KANK1 depletion on cell migration in wound-healing assays were remarkably similar. Treatment of cells with BIG1- or KANK1-specific siRNA interfered significantly with directed cell migration and initial orientation of Golgi/MTOC toward the leading edge, which was not mimicked by KIF21A depletion. Although colocalization of overexpressed KANK1 and endogenous BIG1 in HeLa cells was not clear microscopically, their reciprocal immunoprecipitation (IP) is compatible with the presence of small percentages of each protein in the same complexes. Depletion or overexpression of BIG1 protein appeared not to affect KANK1 distribution. Our data identify actions of both BIG1 and KANK1 in regulating cell polarity during directed migration; these actions are consistent with the presence of both BIG1 and KANK1 in dynamic multimolecular complexes that maintain Golgi/MTOC orientation, differ from those that might contain all three proteins (BIG1, KIF21A, and KANK1), and function in directed transport along microtubules. PMID- 22084093 TI - Glucocorticoid therapy of antigen-induced arthritis depends on the dimerized glucocorticoid receptor in T cells. AB - Despite several side effects, glucocorticoids (GCs) have been widely used for 60 y to treat rheumatoid arthritis on the basis of their antiinflammatory effects. However, the cells targeted by GCs and the transcriptional mechanisms underlying their actions through the glucocorticoid receptor (GR) in steroid therapy remain poorly defined. Using cell type-specific GR-deficient mice subjected to antigen induced arthritis (AIA) as a model of human rheumatoid arthritis, we show that GC action on T cells but not myeloid cells is critical for therapeutic intervention in AIA. Furthermore, the resistance of mice expressing a DNA binding-defective GR (GR(dim)) to GC treatment reveals that dimerization of the GR is indispensable for the antiinflammatory effects. In these mice, the GC-induced suppression of T(H)1 and T(H)17 cell-derived proinflammatory cytokines is impaired. Our finding that IL-17A(-/-) mice are resistant to GC therapy, whereas IFN-gamma(-/-) mice respond as efficiently as WT mice implies that IL-17-producing T cells and not IFN-gamma-producing T cells are the most important targets for an efficient GC therapy. The present study's identification of the critical cell type and the mode of GR action in steroid therapy of AIA significantly advances our understanding of steroid therapy and should lead to therapies with greater efficiency and fewer side effects. PMID- 22084094 TI - Wing patterning gene redefines the mimetic history of Heliconius butterflies. AB - The mimetic butterflies Heliconius erato and Heliconius melpomene have undergone parallel radiations to form a near-identical patchwork of over 20 different wing pattern races across the Neotropics. Previous molecular phylogenetic work on these radiations has suggested that similar but geographically disjunct color patterns arose multiple times independently in each species. The neutral markers used in these studies, however, can move freely across color pattern boundaries, and therefore might not represent the history of the adaptive traits as accurately as markers linked to color pattern genes. To assess the evolutionary histories across different loci, we compared relationships among races within H. erato and within H. melpomene using a series of unlinked genes, genes linked to color pattern loci, and optix, a gene recently shown to control red color-pattern variation. We found that although unlinked genes partition populations by geographic region, optix had a different history, structuring lineages by red color patterns and supporting a single origin of red-rayed patterns within each species. Genes closely linked (80-250 kb) to optix exhibited only weak associations with color pattern. This study empirically demonstrates the necessity of examining phenotype-determining genomic regions to understand the history of adaptive change in rapidly radiating lineages. With these refined relationships, we resolve a long-standing debate about the origins of the races within each species, supporting the hypothesis that the red-rayed Amazonian pattern evolved recently and expanded, causing disjunctions of more ancestral patterns. PMID- 22084095 TI - An antinociceptive role for substance P in acid-induced chronic muscle pain. AB - Release of substance P (SP) from nociceptive nerve fibers and activation of its receptor neurokinin 1 (NK1) are important effectors in the transmission of pain signals. Nonetheless, the role of SP in muscle pain remains unknown. Here we show that a single i.m. acid injection in mice lacking SP signaling by deletion of the tachykinin precursor 1 (Tac1) gene or coadministration of NK1 receptor antagonists produces long-lasting hyperalgesia rather than the transient hyperalgesia seen in control animals. The inhibitory effect of SP was found exclusively in neurons expressing acid-sensing ion channel 3, where SP enhances M channel-like potassium currents through the NK1 receptor in a G protein independent but tyrosine kinase-dependent manner. Furthermore, the SP signaling could alter action potential thresholds and modulate the expression of TTX resistant sodium currents in medium-sized muscle nociceptors. Thus, i.m. SP mediates an unconventional NK1 receptor signal pathway to inhibit acid activation in muscle nociceptors, resulting in an unexpected antinociceptive effect against chronic mechanical hyperalgesia, here induced by repeated i.m. acid injection. PMID- 22084096 TI - Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans. AB - Populations of seasonal influenza virus experience strong annual bottlenecks that pose a considerable extinction risk. It has been suggested that an influenza source population located in tropical Southeast or East Asia seeds annual temperate epidemics. Here we investigate the seasonal dynamics and migration patterns of influenza A H3N2 virus by analysis of virus samples obtained from 2003 to 2006 from Australia, Europe, Japan, New York, New Zealand, Southeast Asia, and newly sequenced viruses from Hong Kong. In contrast to annual temperate epidemics, relatively low levels of relative genetic diversity and no seasonal fluctuations characterized virus populations in tropical Southeast Asia and Hong Kong. Bayesian phylogeographic analysis using discrete temporal and spatial characters reveal high rates of viral migration between urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, this was dependent on virus input from temperate regions and these tropical regions did not maintain a source for annual H3N2 influenza epidemics. We further show that multiple lineages may seed annual influenza epidemics, and that each region may function as a potential source population. We therefore propose that the global persistence of H3N2 influenza A virus is the result of a migrating metapopulation in which multiple different localities may seed seasonal epidemics in temperate regions in a given year. Such complex global migration dynamics may confound control efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses. PMID- 22084097 TI - Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis. AB - Multiwalled carbon nanotubes (MWCNTs) have the potential for widespread applications in engineering and materials science. However, because of their needle-like shape and high durability, concerns have been raised that MWCNTs may induce asbestos-like pathogenicity. Although recent studies have demonstrated that MWCNTs induce various types of reactivities, the physicochemical features of MWCNTs that determine their cytotoxicity and carcinogenicity in mesothelial cells remain unclear. Here, we showed that the deleterious effects of nonfunctionalized MWCNTs on human mesothelial cells were associated with their diameter-dependent piercing of the cell membrane. Thin MWCNTs (diameter ~ 50 nm) with high crystallinity showed mesothelial cell membrane piercing and cytotoxicity in vitro and subsequent inflammogenicity and mesotheliomagenicity in vivo. In contrast, thick (diameter ~ 150 nm) or tangled (diameter ~ 2-20 nm) MWCNTs were less toxic, inflammogenic, and carcinogenic. Thin and thick MWCNTs similarly affected macrophages. Mesotheliomas induced by MWCNTs shared homozygous deletion of Cdkn2a/2b tumor suppressor genes, similar to mesotheliomas induced by asbestos. Thus, we propose that different degrees of direct mesothelial injury by thin and thick MWCNTs are responsible for the extent of inflammogenicity and carcinogenicity. This work suggests that control of the diameter of MWCNTs could reduce the potential hazard to human health. PMID- 22084098 TI - Does evening sun increase the risk of skin cancer? PMID- 22084099 TI - Tripartite motif 8 (TRIM8) modulates TNFalpha- and IL-1beta-triggered NF-kappaB activation by targeting TAK1 for K63-linked polyubiquitination. AB - The tripartite motif (TRIM)-containing proteins are a family of proteins that have been known to be involved in divergent biological processes, including important roles in immune responses through regulating various signaling pathways. In this study, we identified a member of the TRIM family, TRIM8, as a positive regulator of tumor necrosis factor-alpha (TNFalpha) and interleukin 1beta (IL-1beta)-triggered NF-kappaB activation. Overexpression of TRIM8 activated NF-kappaB and potentiated TNFalpha- and IL-1beta-induced activation of NF-kappaB, whereas knockdown of TRIM8 had opposite effects. Coimmunoprecipitations indicated that TRIM8 interacted with TGFbeta activated kinase 1 (TAK1), a serine/threonine kinase essential for TNFalpha- and IL-beta induced NF-kappaB activation. Furthermore, we found that TRIM8 mediated K63 linked polyubiquitination of TAK1 triggered by TNFalpha and IL-1beta. Our findings demonstrate that TRIM8 serves as a critical regulator of TNFalpha- and IL-1beta-induced NF-kappaB activation by mediating K63-linked polyubiquitination of TAK1. PMID- 22084100 TI - Intragenic alternative splicing coordination is essential for Caenorhabditis elegans slo-1 gene function. AB - Alternative splicing is critical for diversifying eukaryotic proteomes, but the rules governing and coordinating splicing events among multiple alternate splice sites within individual genes are not well understood. We developed a quantitative PCR-based strategy to quantify the expression of the 12 transcripts encoded by the Caenorhabditis elegans slo-1 gene, containing three alternate splice sites. Using conditional probability-based models, we show that splicing events are coordinated across these sites. Further, we identify a point mutation in an intron adjacent to one alternate splice site that disrupts alternative splicing at all three sites. This mutation leads to aberrant synaptic transmission at the neuromuscular junction. In a genomic survey, we found that a UAAAUC element disrupted by this mutation is enriched in introns flanking alternate exons in genes with multiple alternate splice sites. These results establish that proper coordination of intragenic alternative splicing is essential for normal physiology of slo-1 in vivo and identify putative specialized cis-regulatory elements that regulate the coordination of intragenic alternative splicing. PMID- 22084101 TI - Profile of Michael Grunstein. PMID- 22084102 TI - Heroin relapse requires long-term potentiation-like plasticity mediated by NMDA2b containing receptors. AB - Persistent relapse to addictive drugs constitutes the most challenging problem in addiction therapy, and is linked to impaired prefrontal cortex regulation of motivated behaviors involving the nucleus accumbens. Using a rat model of heroin addiction, we show that relapse requires long-term potentiation (LTP)-like increases in synaptic strength in the prefrontal cortex projection to the nucleus accumbens. The increased synaptic strength was paralleled by dendritic spine enlargement in accumbens spiny neurons and required up-regulated surface expression of NMDA2b-containing receptors (NR2B). Accordingly, blocking NR2B before reinstating heroin-seeking prevented the induction of LTP-like changes in spine remodeling and synaptic strength, and inhibited heroin relapse. These data show that LTP-like neuroplasticity in prefrontal-accumbens synapses is initiated by NR2B stimulation and strongly contributes to heroin relapse. Moreover, the data reveal NR2B-containing NMDA receptors as a previously unexplored therapeutic target for treating heroin addiction. PMID- 22084103 TI - Dynamic social networks promote cooperation in experiments with humans. AB - Human populations are both highly cooperative and highly organized. Human interactions are not random but rather are structured in social networks. Importantly, ties in these networks often are dynamic, changing in response to the behavior of one's social partners. This dynamic structure permits an important form of conditional action that has been explored theoretically but has received little empirical attention: People can respond to the cooperation and defection of those around them by making or breaking network links. Here, we present experimental evidence of the power of using strategic link formation and dissolution, and the network modification it entails, to stabilize cooperation in sizable groups. Our experiments explore large-scale cooperation, where subjects' cooperative actions are equally beneficial to all those with whom they interact. Consistent with previous research, we find that cooperation decays over time when social networks are shuffled randomly every round or are fixed across all rounds. We also find that, when networks are dynamic but are updated only infrequently, cooperation again fails. However, when subjects can update their network connections frequently, we see a qualitatively different outcome: Cooperation is maintained at a high level through network rewiring. Subjects preferentially break links with defectors and form new links with cooperators, creating an incentive to cooperate and leading to substantial changes in network structure. Our experiments confirm the predictions of a set of evolutionary game theoretic models and demonstrate the important role that dynamic social networks can play in supporting large-scale human cooperation. PMID- 22084104 TI - Developmental stalling and organ-autonomous regulation of morphogenesis. AB - Timing of organ development during embryogenesis is coordinated such that at birth, organ and fetal size and maturity are appropriately proportioned. The extent to which local developmental timers are integrated with each other and with the signaling interactions that regulate morphogenesis to achieve this end is not understood. Using the absolute requirement for a signaling pathway activity (bone morphogenetic protein, BMP) during a critical stage of tooth development, we show that suboptimal levels of BMP signaling do not lead to abnormal morphogenesis, as suggested by mutants affecting BMP signaling, but to a 24-h stalling of the intrinsic developmental clock of the tooth. During this time, BMP levels accumulate to reach critical levels whereupon tooth development restarts, accelerates to catch up with development of the rest of the embryo and completes normal morphogenesis. This suggests that individual organs can autonomously control their developmental timing to adjust their stage of development to that of other organs. We also find that although BMP signaling is critical for the bud-to-cap transition in all teeth, levels of BMP signaling are regulated differently in multicusped teeth. We identify an interaction between two homeodomain transcription factors, Barx1 and Msx1, which is responsible for setting critical levels of BMP activity in multicusped teeth and provides evidence that correlates the levels of Barx1 transcriptional activity with cuspal complexity. This study highlights the importance of absolute levels of signaling activity for development and illustrates remarkable self-regulation in organogenesis that ensures coordination of developmental processes such that timing is subordinate to developmental structure. PMID- 22084105 TI - Acrosome-reacted mouse spermatozoa recovered from the perivitelline space can fertilize other eggs. AB - Many investigators maintain that spermatozoa that have initiated the acrosome reaction (AR) before reaching the surface of the egg's zona pellucida (ZP) are unable to bind and penetrate the ZP. A recent study has revealed that most fertilizing mouse spermatozoa initiate the AR before contacting the ZP. We found that acrosome-reacted spermatozoa collected from the perivitelline space of Cd9 null mice (whose egg plasma membranes are incapable of fusing with spermatozoa) were able to pass through both the cumulus and ZP of WT mouse eggs and produced live offspring. This means that the spermatozoa we used had the ability to pass through the ZP at least twice. Apparently, some spermatozoa that had undergone the AR long before contact with the ZP remained capable of crossing the ZP and fertilizing eggs. Thus, the concept that acrosome-reacted spermatozoa are unable to bind to the ZP and have lost their fertilizing capacity must be reconsidered. PMID- 22084106 TI - alpha-Oscillations in the monkey sensorimotor network influence discrimination performance by rhythmical inhibition of neuronal spiking. AB - Extensive work in humans using magneto- and electroencephalography strongly suggests that decreased oscillatory alpha-activity (8-14 Hz) facilitates processing in a given region, whereas increased alpha-activity serves to actively suppress irrelevant or interfering processing. However, little work has been done to understand how alpha-activity is linked to neuronal firing. Here, we simultaneously recorded local field potentials and spikes from somatosensory, premotor, and motor regions while a trained monkey performed a vibrotactile discrimination task. In the local field potentials we observed strong activity in the alpha-band, which decreased in the sensorimotor regions during the discrimination task. This alpha-power decrease predicted better discrimination performance. Furthermore, the alpha-oscillations demonstrated a rhythmic relation with the spiking, such that firing was highest at the trough of the alpha-cycle. Firing rates increased with a decrease in alpha-power. These findings suggest that alpha-oscillations exercise a strong inhibitory influence on both spike timing and firing rate. Thus, the pulsed inhibition by alpha-oscillations plays an important functional role in the extended sensorimotor system. PMID- 22084107 TI - Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition. AB - Individuals who are homozygous for the G allele of the rs53576 SNP of the oxytocin receptor (OXTR) gene tend to be more prosocial than carriers of the A allele. However, little is known about how these differences manifest behaviorally and whether they are readily detectable by outside observers, both critical questions in theoretical accounts of prosociality. In the present study, we used thin-slicing methodology to test the hypotheses that (i) individual differences in rs53576 genotype predict how prosocial observers judge target individuals to be on the basis of brief observations of behavior, and (ii) that variation in targets' nonverbal displays of affiliative cues would account for these judgment differences. In line with predictions, we found that individuals homozygous for the G allele were judged to be more prosocial than carriers of the A allele. These differences were completely accounted for by variations in the expression of affiliative cues. Thus, individual differences in rs53576 are associated with behavioral manifestations of prosociality, which ultimately guide the judgments others make about the individual. PMID- 22084108 TI - Oceanic islands are not sinks of biodiversity in spore-producing plants. AB - Islands have traditionally been considered as migratory and evolutionary dead ends for two main reasons: island colonizers are typically assumed to lose their dispersal power, and continental back colonization has been regarded as unlikely because of niche preemption. The hypothesis that islands might actually represent dynamic refugia and migratory stepping stones for species that are effective dispersers, and in particular, for spore-producing plants, is formally tested here, using the archipelagos of the Azores, Canary Islands, and Madeira, as a model. Population genetic analyses based on nuclear microsatellite variation indicate that dispersal ability of the moss Platyhypnidium riparioides does not decrease in the island setting. The analyses further show that, unlike island populations, mainland (southwestern Europe and North Africa) populations underwent a severe bottleneck during the last glacial maximum (LGM). Our results thus refute the traditional view of islands as the end of the colonization road and point to a different perception of North Atlantic archipelagos as major sources of biodiversity for the postglacial recolonization of Europe by spore producing plants. PMID- 22084109 TI - QnAs with Bruce M. Spiegelman. PMID- 22084110 TI - Ecological mechanisms underlying the sustainability of the agricultural heritage rice-fish coculture system. AB - For centuries, traditional agricultural systems have contributed to food and livelihood security throughout the world. Recognizing the ecological legacy in the traditional agricultural systems may help us develop novel sustainable agriculture. We examine how rice-fish coculture (RF), which has been designated a "globally important agricultural heritage system," has been maintained for over 1,200 y in south China. A field survey demonstrated that although rice yield and rice-yield stability are similar in RF and rice monoculture (RM), RF requires 68% less pesticide and 24% less chemical fertilizer than RM. A field experiment confirmed this result. We documented that a mutually beneficial relationship between rice and fish develops in RF: Fish reduce rice pests and rice favors fish by moderating the water environment. This positive relationship between rice and fish reduces the need for pesticides in RF. Our results also indicate a complementary use of nitrogen (N) between rice and fish in RF, resulting in low N fertilizer application and low N release into the environment. These findings provide unique insights into how positive interactions and complementary use of resource between species generate emergent ecosystem properties and how modern agricultural systems might be improved by exploiting synergies between species. PMID- 22084111 TI - POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to multiple transporters. AB - Specialized proteins in the plasma membrane, endoplasmic reticulum (ER), and mitochondria tightly regulate intracellular calcium. A unique mechanism called store-operated calcium entry is activated when ER calcium is depleted, serving to restore intra-ER calcium levels. An ER calcium sensor, stromal interaction molecule 1 (STIM1), translocates within the ER membrane upon store depletion to the juxtaplasma membrane domain, where it interacts with intracellular domains of a highly calcium-selective plasma membrane ion channel, Orai1. STIM1 gates Orai1, allowing calcium to enter the cytoplasm, where it repletes the ER store via calcium-ATPases pumps. Here, we performed affinity purification of Orai1 from Jurkat cells to identify partner of STIM1 (POST), a 10-transmembrane-spanning segment protein of unknown function. The protein is located in the plasma membrane and ER. POST-Orai1 binding is store depletion-independent. On store depletion, the protein binds STIM1 and moves within the ER to localize near the cell membrane. This protein, TMEM20 (POST), does not affect store-operated calcium entry but does reduce plasma membrane Ca(2+) pump activity. Store depletion promotes STIM1-POST complex binding to smooth ER and plasma membrane Ca(2+) ATPases (SERCAs and PMCAs, respectively), Na/K-ATPase, as well as to the nuclear transporters, importins-beta and exportins. PMID- 22084112 TI - Different levels of the Tripartite motif protein, Anomalies in sensory axon patterning (Asap), regulate distinct axonal projections of Drosophila sensory neurons. AB - The axonal projection pattern of sensory neurons typically is regulated by environmental signals, but how different sensory afferents can establish distinct projections in the same environment remains largely unknown. Drosophila class IV dendrite arborization (C4da) sensory neurons project subtype-specific axonal branches in the ventral nerve cord, and we show that the Tripartite motif protein, Anomalies in sensory axon patterning (Asap) is a critical determinant of the axonal projection patterns of different C4da neurons. Asap is highly expressed in C4da neurons with both ipsilateral and contralateral axonal projections, but the Asap level is low in neurons that have only ipsilateral projections. Mutations in asap cause a specific loss of contralateral projections, whereas overexpression of Asap induces ectopic contralateral projections in C4da neurons. We also show by biochemical and genetic analysis that Asap regulates Netrin signaling, at least in part by linking the Netrin receptor Frazzled to the downstream effector Pico. In the absence of Asap, the sensory afferent connectivity within the ventral nerve cord is disrupted, resulting in specific larval behavioral deficits. These results indicate that different levels of Asap determine distinct patterns of axonal projections of C4da neurons by modulating Netrin signaling and that the Asap-mediated axonal projection is critical for assembly of a functional sensory circuit. PMID- 22084113 TI - Parasitoid-specific induction of plant responses to parasitized herbivores affects colonization by subsequent herbivores. AB - Plants are exposed to a suite of herbivorous attackers that often arrive sequentially. Herbivory affects interactions between the host plants and subsequently attacking herbivores. Moreover, plants may respond to herbivory by emitting volatile organic compounds (VOCs) that attract carnivorous natural enemies of the herbivores. However, information borne by VOCs is ubiquitous and may attract carnivores, such as parasitoids, that differ in their effectiveness at releasing the plant from its herbivorous attackers. Furthermore, the development of parasitoids within their herbivorous hosts, attacking a given host plant, may influence the elicitation of defensive reactions in the host plant. This may, in turn, affect the behavior of subsequent herbivores attacking the host plant. Here, we show that the species identity of a parasitoid had a more significant effect on defense responses of Brassica oleracea plants than the species identity of the herbivorous hosts of the parasitoids. Consequently, B. oleracea plants that were damaged by caterpillars (Pieris spp.) parasitized by different parasitoid species varied in the degree to which diamondback moths (Plutella xylostella) selected the plants for oviposition. Attracting parasitoids in general benefitted the plants by reducing diamondback moth colonization. However, the species of parasitoid that parasitized the herbivore significantly affected the magnitude of this benefit by its species-specific effect on herbivore-plant interactions mediated by caterpillar regurgitant. Our findings show that information-mediated indirect defense may lead to unpredictable consequences for plants when considering trait-mediated effects of parasitized caterpillars on the host plant and their consequences because of community-wide responses to induced plants. PMID- 22084114 TI - Modeling rotavirus strain dynamics in developed countries to understand the potential impact of vaccination on genotype distributions. AB - Understanding how immunity shapes the dynamics of multistrain pathogens is essential in determining the selective pressures imposed by vaccines. There is currently much interest in elucidating the strain dynamics of rotavirus to determine whether vaccination may lead to the replacement of vaccine-type strains. In developed countries, G1P[8] strains constitute the majority of rotavirus infections most years, but occasionally other genotypes dominate for reasons that are not well understood. We developed a mathematical model to examine the interaction of five common rotavirus genotypes. We explored a range of estimates for the relative strength of homotypic vs. heterotypic immunity and compared model predictions against observed genotype patterns from six countries. We then incorporated vaccination in the model to examine its impact on rotavirus incidence and the distribution of strains. Our model can explain the coexistence and cyclical pattern in the distribution of genotypes observed in most developed countries. The predicted frequency of cycling depends on the relative strength of homotypic vs. heterotypic immunity. Vaccination that provides strong protection against G1 and weaker protection against other strains will likely lead to an increase in the relative prevalence of non-G1 strains, whereas a vaccine that provides equally strong immunity against all strains may promote the continued predominance of G1. Overall, however, disease incidence is expected to be substantially reduced under both scenarios and remain below prevaccination levels despite the possible emergence of new strains. Better understanding of homotypic vs. heterotypic immunity, both natural and vaccine-induced, will be critical in predicting the impact of vaccination. PMID- 22084116 TI - Shedding light on the vitamin D-tuberculosis-HIV connection. PMID- 22084115 TI - Crystal structure of the Lassa virus nucleoprotein-RNA complex reveals a gating mechanism for RNA binding. AB - Arenaviruses cause disease in industrialized and developing nations alike. Among them, the hemorrhagic fever virus Lassa is responsible for ~300,000-500,000 infections/y in Western Africa. The arenavirus nucleoprotein (NP) forms the protein scaffold of the genomic ribonucleoprotein complexes and is critical for transcription and replication of the viral genome. Here, we present crystal structures of the RNA-binding domain of Lassa virus NP in complex with ssRNA. This structure shows, in contrast to the predicted model, that RNA binds in a deep, basic crevice located entirely within the N-terminal domain. Furthermore, the NP-ssRNA structures presented here, combined with hydrogen-deuterium exchange/MS and functional studies, suggest a gating mechanism by which NP opens to accept RNA. Directed mutagenesis and functional studies provide a unique look into how the arenavirus NPs bind to and protect the viral genome and also suggest the likely assembly by which viral ribonucleoprotein complexes are organized. PMID- 22084117 TI - LRRC52 (leucine-rich-repeat-containing protein 52), a testis-specific auxiliary subunit of the alkalization-activated Slo3 channel. AB - KSper, a pH-dependent K(+) current in mouse spermatozoa that is critical for fertility, is activated by alkalization in the range of pH 6.4-7.2 at membrane potentials between -50 and 0 mV. Although the KSper pore-forming subunit is encoded by the Slo3 gene, heterologously expressed Slo3 channels are largely closed at potentials negative to 0 mV at physiological pH. Here we identify a Slo3-associating protein, LRRC52 (leucine-rich repeat-containing 52), that shifts Slo3 gating into a range of voltages and pH values similar to that producing KSper current activation. Message for LRRC52, a homolog of the Slo1-modifying LRRC26 protein, is enriched in testis relative to other homologous LRRC subunits and is developmentally regulated in concert with that for Slo3. LRRC52 protein is detected only in testis. It is markedly diminished from Slo3(-/-) testis and completely absent from Slo3(-/-) sperm, indicating that LRRC52 expression is critically dependent on the presence of Slo3. We also examined the ability of other LRRC subunits homologous to LRRC26 and LRRC52 to modify Slo3 currents. Although both LRRC26 and LRRC52 are able to modify Slo3 function, LRRC52 is the stronger modifier of Slo3 function. Effects of other related subunits were weaker or absent. We propose that LRRC52 is a testis-enriched Slo3 auxiliary subunit that helps define the specific alkalization dependence of KSper activation. Together, LRRC52 and LRRC26 define a new family of auxiliary subunits capable of critically modifying the gating behavior of Slo family channels. PMID- 22084118 TI - Construction of regulatory networks using expression time-series data of a genotyped population. AB - The inference of regulatory and biochemical networks from large-scale genomics data is a basic problem in molecular biology. The goal is to generate testable hypotheses of gene-to-gene influences and subsequently to design bench experiments to confirm these network predictions. Coexpression of genes in large scale gene-expression data implies coregulation and potential gene-gene interactions, but provide little information about the direction of influences. Here, we use both time-series data and genetics data to infer directionality of edges in regulatory networks: time-series data contain information about the chronological order of regulatory events and genetics data allow us to map DNA variations to variations at the RNA level. We generate microarray data measuring time-dependent gene-expression levels in 95 genotyped yeast segregants subjected to a drug perturbation. We develop a Bayesian model averaging regression algorithm that incorporates external information from diverse data types to infer regulatory networks from the time-series and genetics data. Our algorithm is capable of generating feedback loops. We show that our inferred network recovers existing and novel regulatory relationships. Following network construction, we generate independent microarray data on selected deletion mutants to prospectively test network predictions. We demonstrate the potential of our network to discover de novo transcription-factor binding sites. Applying our construction method to previously published data demonstrates that our method is competitive with leading network construction algorithms in the literature. PMID- 22084120 TI - Wnt signaling and a Smad pathway blockade direct the differentiation of human pluripotent stem cells to multipotent neural crest cells. AB - Neural crest stem cells can be isolated from differentiated cultures of human pluripotent stem cells, but the process is inefficient and requires cell sorting to obtain a highly enriched population. No specific method for directed differentiation of human pluripotent cells toward neural crest stem cells has yet been reported. This severely restricts the utility of these cells as a model for disease and development and for more applied purposes such as cell therapy and tissue engineering. In this report, we use small-molecule compounds in a single step method for the efficient generation of self-renewing neural crest-like stem cells in chemically defined media. This approach is accomplished directly from human pluripotent cells without the need for coculture on feeder layers or cell sorting to obtain a highly enriched population. Critical to this approach is the activation of canonical Wnt signaling and concurrent suppression of the Activin A/Nodal pathway. Over 12-14 d, pluripotent cells are efficiently specified along the neuroectoderm lineage toward p75(+) Hnk1(+) Ap2(+) neural crest-like cells with little or no contamination by Pax6(+) neural progenitors. This cell population can be clonally amplified and maintained for >25 passages (>100 d) while retaining the capacity to differentiate into peripheral neurons, smooth muscle cells, and mesenchymal precursor cells. Neural crest-like stem cell derived mesenchymal precursors have the capacity for differentiation into osteocytes, chondrocytes, and adipocytes. In sum, we have developed methods for the efficient generation of self-renewing neural crest stem cells that greatly enhance their potential utility in disease modeling and regenerative medicine. PMID- 22084121 TI - Constitutive exposure of phosphatidylserine on viable cells. AB - Apoptotic cells are quickly recognized and engulfed by phagocytes to prevent the release of noxious materials from dying cells. Phosphatidylserine (PS) exposed on the surface of apoptotic cells is a proposed "eat-me" signal for the phagocytes. Transmembrane protein 16F (TMEM16F), a membrane protein with eight transmembrane segments, has the Ca-dependent phospholipid scramblase activity. Here we show that when lymphoma cells were transformed with a constitutively active form of TMEM16F, they exposed a high level of PS that was comparable to that observed on apoptotic cells. The PS-exposing cells were morphologically normal and grew normally. They efficiently responded to interleukin 3 and underwent apoptosis upon treatment with Fas ligand. The viable PS-exposing cells bound to peritoneal macrophages at 4 degrees C, but not at 25 degrees C. Accordingly, these cells were not engulfed by macrophages. When apoptotic cells were injected i.v. into mice, they were phagocytosed by CD11c(+)CD8(+) dendritic cells (DCs) in the spleen, but the PS-exposing living cells were not phagocytosed by these DCs. Furthermore, when PS-exposing lymphoma cells were transplanted s.c. into nude mice, they generated tumors as efficiently as parental lymphoma cells that did not expose PS. These results indicated that PS exposure alone is not sufficient to be recognized by macrophages as an eat-me signal. PMID- 22084122 TI - Cholesterol level and statin use in Alzheimer disease: II. Review of human trials and recommendations. AB - Substantial evidence has accumulated in support of the hypothesis that elevated cholesterol levels increase the risk of developing Alzheimer disease (AD). As a result, much work has investigated the potential use of lipid-lowering agents, particularly statins, as preventive or therapeutic agents for AD. Although epidemiology and preclinical statin research (described in part I of this review) have generally supported an adverse role of high cholesterol levels regarding AD, human studies of statins (reviewed herein) show highly variable outcomes, making it difficult to draw firm conclusions. We identify several confounding factors among the human studies, including differing blood-brain barrier permeabilities among statins, the stage in AD at which statins were administered, and the drugs' pleiotropic metabolic effects, all of which contribute to the substantial variability observed to date. We recommend that future human studies of this important therapeutic topic (1) take the blood-brain barrier permeabilities of statins into account when analyzing results, (2) include specific analyses of the effects on low- and high-density lipoprotein cholesterol, and, most important, (3) conduct statin treatment trials solely in patients with mild AD, who have the best chance for disease modification. PMID- 22084123 TI - Coping with death and dying on a neurology inpatient service: death rounds as an educational initiative for residents. AB - BACKGROUND: Residents in neurology may feel unprepared to care for dying patients. We developed Death Rounds to provide emotional support and end-of-life care teaching for residents caring for dying patients on the inpatient neurology service. Death Rounds are monthly 1-hour clinical case discussions where residents identify issues through shared experiences. OBJECTIVE: To survey neurology residents' perceptions of Death Rounds with respect to end-of-life care teaching and emotional support. Design, Setting, and PARTICIPANTS: We conducted an electronic survey of all (n = 26) neurology residents and recent residency graduates at the University of Washington 2 years after instituting monthly Death Rounds. Main Outcome Measure The survey consisted of 10 questions examining residents' perceptions of the extent to which Death Rounds provided emotional support and end-of-life care teaching. We dichotomized responses to statements about Death Rounds as agree or disagree. RESULTS: All 26 residents responded to the survey and attended at least 1 Death Rounds session. More than half of residents attended more than 3 sessions. Residents agreed that Death Rounds helped them cope with dying patients (17 residents [65%]), delivered closure for the team (16 residents [61%]), and provided emotional support, more for the team (18 residents [69%]) than the individual (10 residents [38%]). Most residents felt that Death Rounds provided useful teaching about end-of-life care (18 residents [69%]), and they were satisfied overall with Death Rounds (16 residents [61%]). CONCLUSIONS: Death Rounds afford an opportunity for physicians-in training to process as a group their feelings, intense emotions, and insecurities while learning from the dying process. In our inpatient neurology service, most residents found it a rewarding and valuable experience. PMID- 22084124 TI - Interferon beta-1b for the treatment of primary progressive multiple sclerosis: five-year clinical trial follow-up. AB - OBJECTIVES: To investigate, during the 5-year period without treatment after termination of a 2-year clinical trial of interferon beta-1b for the treatment of primary progressive multiple sclerosis, differences in the evolution of clinical variables and magnetic resonance imaging results between trial arms and to investigate correlations between in-trial changes in Multiple Sclerosis Functional Composite (MSFC) score and magnetic resonance imaging variables and Expanded Disability Status Scale (EDSS) score evolution. DESIGN: Five-year clinical trial follow-up. SETTING: Clinical Neuroimmunology Unit, Multiple Sclerosis Centre of Catalonia, Autonomous University of Barcelona, Spain. Patients Seventy-three patients received interferon beta-1b or placebo during the trial. MAIN OUTCOME MEASURES: After 5 years without treatment, the EDSS and MSFC measures were scored for 63 and 59 patients, respectively. Neuropsychological and magnetic resonance imaging assessments were performed for 59 and 50 patients, respectively. RESULTS: After 5 years without treatment, the interferon beta-1b group had better 9-Hole Peg Test (P = .02) and Word List Generation Test (P < .001) scores, and their magnetization transfer ratio measures in the normal-appearing white matter were significantly higher (P = .02, P = .009, and P = .03 for the mean, peak location, and peak height magnetic transfer ratios, respectively). During the entire study period (from trial baseline to assessment at 5 years without treatment), the placebo group showed a greater decrease in brain parenchymal fraction (P = .004). The in-trial increase of lesions correlated with the worsening of the EDSS score during the 5-year period without treatment (P = .004). CONCLUSIONS: Modest but beneficial effects of interferon beta-1b on clinical variables and brain atrophy development were observed 5 years after trial termination. Moreover, in-trial lesion activity correlated with EDSS progression after trial termination. Therefore, we provide evidence to consider immunomodulation as a sensible approach to treat primary progressive multiple sclerosis. PMID- 22084125 TI - Natalizumab and impedance of the homing of CD34+ hematopoietic progenitors. AB - BACKGROUND: Treatment with natalizumab, an antibody blocking the alpha4-integrin, is associated with increased numbers of circulating CD34+ cells in the peripheral blood of patients with multiple sclerosis. OBJECTIVE: To determine whether natalizumab mobilizes CD34+ cells from or inhibits homing to the bone marrow (BM). DESIGN: Fifty-two patients with relapsing-remitting multiple sclerosis treated with natalizumab were included. Flow cytometric analyses; polymerase chain reaction assays for JC (John Cunningham) virus DNA detection; and adhesion, migration, and apoptosis assays of immunomagnetically enriched peripheral blood and BM CD34+ cells were conducted. A comparison was made with CD34+ cells from granulocyte colony-stimulating factor-mobilized peripheral blood or steady-state BM of age- and sex-matched healthy donors. RESULTS: We found adhesion and migration of peripheral blood-derived CD34+ cells to be reduced. In BM aspirates from natalizumab-treated patients, the cellularity, the proportion, and the adhesive capacity of CD34+ cells were normal. The JC virus was undetectable. CONCLUSIONS: Natalizumab mediates an increase in circulating CD34+ cells by interfering with homing to the BM. Thus, CD34+ cells appear unlikely to represent a source mobilizing JC virus out of the BM in patients treated with natalizumab. PMID- 22084126 TI - Brain involvement in neuromyelitis optica spectrum disorders. AB - BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSDs) are severe inflammatory demyelinating disorders of the central nervous system. Brain involvement is increasingly recognized. OBJECTIVE: To study brain involvement in NMOSDs among Hong Kong Chinese patients. DESIGN: Retrospective study of patients with NMOSDs. SETTING: Tertiary medical center in Hong Kong. Patients Thirty-four Hong Kong Chinese patients with NMOSDs of 2 years or longer were recruited. INTERVENTIONS: Brain and spinal cord magnetic resonance imaging was performed during NMOSD attacks and was repeated yearly for the first 3 years. MAIN OUTCOME MEASURES: We evaluated clinical features of NMOSDs associated with brain involvement and brain lesions on magnetic resonance imaging. RESULTS: Among 34 patients with NMOSDs of 2 years or longer, 20 (59%) had brain involvement. The mean age at onset among these 20 patients was 45.6 years (age range, 19-67 years); 18 were women. Eleven patients (32% of all the patients with NMOSDs) had clinical manifestation of brain involvement, 19 patients (56%) had brain abnormalities on magnetic resonance imaging consistent with inflammatory demyelination, and 2 patients (6%) fulfilled criteria for multiple sclerosis. Clinical manifestation of brain involvement included the following: trigeminal neuralgia; vomiting, vertigo, ataxia, dysphagia, and tetraparesis from lesions around the third and fourth ventricles and aqueduct; homonymous hemianopia, aphasia, hemiparesis, and cognitive impairment from extensive hemispheric white matter lesions; and ataxia, diplopia, hiccups, facial sensory loss, internuclear ophthalmoplegia, hemisensory loss, and hemiparesis from other lesions in the midbrain, pons, cerebellar peduncles, and medulla. Eight patients (24%) developed brainstem encephalitis clinically, and brainstem encephalitis was the initial clinical manifestation in 6 patients (18%). Brain abnormalities on magnetic resonance imaging were detected in brainstem in 15 patients (44%), hemispheric periventricular white matter in 7 patients (21%), deep white matter in 7 patients (21%), corpus callosum in 4 patients (12%), subcortical white matter in 3 patients (9%), thalamus in 2 patients (6%), hypothalamus in 1 patient (3%), basal ganglia in 1 patient (3%), internal capsule in 1 patient (3%), periaqueductal gray matter in 1 patient (3%), and around the third and fourth ventricles in 1 patient (3%); large confluent lesions were detected in 2 patients (6%). CONCLUSION: Brain involvement manifesting clinically as brainstem encephalitis is common among Hong Kong Chinese patients with NMOSDs. PMID- 22084127 TI - SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. AB - BACKGROUND: The SQSTM1 gene encodes p62, a major pathologic protein involved in neurodegeneration. OBJECTIVE: To examine whether SQSTM1 mutations contribute to familial and sporadic amyotrophic lateral sclerosis (ALS). DESIGN: Case-control study. SETTING: Academic research. Patients A cohort of 546 patients with familial (n = 340) or sporadic (n = 206) ALS seen at a major academic referral center were screened for SQSTM1 mutations. MAIN OUTCOME MEASURES: We evaluated the distribution of missense, deletion, silent, and intronic variants in SQSTM1 among our cohort of patients with ALS. In silico analysis of variants was performed to predict alterations in p62 structure and function. RESULTS: We identified 10 novel SQSTM1 mutations (9 heterozygous missense and 1 deletion) in 15 patients (6 with familial ALS and 9 with sporadic ALS). Predictive in silico analysis classified 8 of 9 missense variants as pathogenic. CONCLUSIONS: Using candidate gene identification based on prior biological knowledge and the functional prediction of rare variants, we identified several novel SQSTM1 mutations in patients with ALS. Our findings provide evidence of a direct genetic role for p62 in ALS pathogenesis and suggest that regulation of protein degradation pathways may represent an important therapeutic target in motor neuron degeneration. PMID- 22084128 TI - Prefrontal cortex and executive function impairments in primary breast cancer. AB - OBJECTIVES: To examine differences in prefrontal-executive function between breast cancer (BC) survivors with and without a history of chemotherapy treatment compared with healthy control women and to determine the associations between prefrontal cortex deficits and behavioral impairments, as well as certain demographic and disease variables. DESIGN: Observational study. SETTING: University-based research facility. PARTICIPANTS: Twenty-five women with BC who had received chemotherapy, 19 women with BC who had not received chemotherapy, and 18 healthy female controls, all matched for age and other demographic variables. RESULTS: Women with BC demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls. The chemotherapy group also demonstrated significantly reduced left caudal lateral prefrontal cortex activation and increased perseverative errors and reduced processing speed compared with the other 2 groups. Reduced left caudal lateral prefrontal cortex activation was significantly correlated with higher disease severity and elevated subjective executive dysfunction in the chemotherapy-treated women. Older age and lower educational level were associated with increased executive function impairment in the chemotherapy group. CONCLUSIONS: These findings provide further evidence of neurological impairment associated with primary BC irrespective of treatment history. The left caudal lateral prefrontal region may be particularly vulnerable to the effects of chemotherapy and/or disease severity and may represent a novel biomarker of subjective executive dysfunction in chemotherapy-treated women. Furthermore, negative effects of chemotherapy on brain function may be exacerbated by such factors as increased age and lower educational level. PMID- 22084129 TI - Relationship between chronic atrial fibrillation and worse outcomes in stroke patients after intravenous thrombolysis. AB - BACKGROUND: It is unclear whether stroke patients with atrial fibrillation (AF) are prone to adverse outcomes following treatment with intravenous recombinant tissue plasminogen activator, and whether the burden of AF affects these outcomes. OBJECTIVE: To investigate the contribution of AF (whether it be a first detected episode of AF or chronic AF) to stroke outcomes in patients treated with intravenous recombinant tissue plasminogen activator. DESIGN: Retrospective study. SETTING: Academic hospital. Patients Consecutive patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator within 3 hours from symptom onset were included. Vascular risk factors, stroke characteristics, and outcome measures were compared between patients with and without AF. MAIN OUTCOME MEASURES: Symptomatic intracranial hemorrhage and poor functional recovery (modified Rankin Scale score of >2). RESULTS: Of the 214 patients who were studied (mean [SD] age, 74 [14] years, with 50% of patients being men), 21 had a first-detected episode of AF, and 55 had chronic AF. The incidence of symptomatic intracranial hemorrhage was significantly higher in patients with chronic AF than in patients without AF (16% vs 5%), and the incidence of poor functional recovery was significantly higher in patients with chronic AF than in patients without AF (62% vs 44%). The increase in risk of symptomatic intracranial hemorrhage (but not in poor functional recovery) among patients with chronic AF remained significant after adjusting for age and baseline National Institutes of Health Stroke Scale score (odds ratio, 2.95 [95% CI, 1.12-9.30]). Patients with chronic AF who developed a symptomatic intracranial hemorrhage had a longer duration of AF than those who did not (59 vs 23 months), and patients with chronic AF who had a poor functional recovery had a longer duration of AF than those who did not (36 vs 16 months) (P < .05). By contrast, there were no differences in outcomes between patients with a first detected episode of AF and those without AF, and between patients with paroxysmal AF and those with persistent or permanent AF. CONCLUSIONS: Patients with chronic AF have worse stroke outcomes than do patients without AF, and the risk for worse outcomes was greater in patients with a longer duration of AF. PMID- 22084130 TI - Clusterin as an Alzheimer biomarker. PMID- 22084132 TI - New type of cortical neuroplasticity after nerve repair in brachial plexus lesions. AB - BACKGROUND: In brachial plexus avulsion, a recent technique connects the ending of the disrupted musculocutaneous nerve to the side of the intact phrenic nerve to regain elbow flexion. This requires the phrenic nerve to perform a new double function: independent control of breathing and elbow flexion. Neuroplastic changes associated with acquisition of double nerve functions have not yet been investigated. OBJECTIVE: To evaluate neuroplastic changes associated with acquisition of double nerve functions in a monofunctional nerve (phrenic nerve). DESIGN: Clinical and functional magnetic resonance imaging investigations during arm movements, forced inspiration, and motor control tasks. SETTING: Investigations at the Medical University of Vienna, Vienna, Austria. PARTICIPANTS: Three healthy control subjects, 2 patients with phrenic nerve end to-side coaptation, and 1 control patient with C7 end-to-end coaptation (same clinical presentation but phrenic nerve unchanged). RESULTS: Clinical documentation showed that both patients with phrenic nerve end-to-side coaptation were able to control the diaphragm and the biceps independently via the same phrenic nerve. In contrast to all controls, both patients with phrenic nerve end to-side coaptation activated the cortical diaphragm areas with flexion of the diseased arm. CONCLUSION: Our functional magnetic resonance imaging data indicate that the patient's cortical diaphragm areas reorganize in such a way that independent control of breathing and elbow flexion is possible with the same neuronal population. PMID- 22084131 TI - Positron emission tomography and neuropathologic estimates of fibrillar amyloid beta in a patient with Down syndrome and Alzheimer disease. AB - BACKGROUND: Down syndrome appears to be associated with a virtually certain risk of fibrillar amyloid-beta (Abeta) pathology by the age of 40 and a very high risk of dementia at older ages. The positron emission tomography (PET) ligand florbetapir F18 has been shown to characterize fibrillar Abeta in the living human brain and to provide a close correlation with subsequent Abeta neuropathology in individuals proximate to and after the end of life. The extent to which the most frequently used PET ligands can be used to detect fibrillar Abeta in patients with Down syndrome remains to be determined. OBJECTIVES: To characterize PET estimates of fibrillar Abeta burden in a Down syndrome patient very close to the end of life and to compare them with neuropathologic assessment made after his death. Design/ METHODS: With the family's informed consent, florbetapir PET was used to study a 55-year-old Down syndrome patient with Alzheimer disease near the end of life; his brain was donated for neuropathologic assessment when he died 14 days later. Visual ratings of cerebral florbetapir uptake were performed by trained readers who were masked to the patient's diagnosis as part of a larger study, and an automated algorithm was used to characterize regional-to-cerebellar standard uptake value ratios in 6 cerebral regions of interest. Neuropathologic assessments were performed masked to the patient's diagnosis or PET measurements. RESULTS: Visual ratings and automated analyses of the PET image revealed a heavy fibrillar Abeta burden in cortical, striatal, and thalamic regions, similar to that reported for patients with late onset Alzheimer disease. This matched neuropathologic findings of frequent neuritic and diffuse plaques, as well as frequent amyloid angiopathy, except for neuropathologically demonstrated frequent cerebellar diffuse plaques and amyloid angiopathy that were not detected by the PET scan. CONCLUSIONS: Florbetapir PET can be used to detect increased cerebral-to-cerebellar fibrillar Abeta burden in a Down syndrome patient with Alzheimer disease, even in the presence of frequent amyloid angiopathy and diffuse plaques in the cerebellum. Additional studies are needed to determine the extent to which PET could be used to detect and to track fibrillar Abeta and to evaluate investigational Abeta-modifying treatments in the presymptomatic and symptomatic stages of Alzheimer disease. PMID- 22084133 TI - Whipple limbic encephalitis. AB - OBJECTIVE: To describe a relapse of Whipple disease revealed by isolated limbic encephalitis with no other signs of systemic involvement. DESIGN: Case report. SETTING: University Hospital of Strasbourg, Strasbourg, France. Patient A 41 year-old patient. MAIN OUTCOME MEASURES: Cognitive functions and results of cerebrospinal fluid analysis and brain magnetic resonance imaging. RESULTS: A 41 year-old patient was hospitalized for headache associated with anterograde amnesia and temporospatial disorientation. Whipple disease with systemic manifestations was diagnosed 4 years previously and insufficiently treated. The neuropsychological evaluation showed impaired episodic memory and executive functions. Analysis of the cerebrospinal fluid showed increased lymphocytes and a positive Tropheryma whipplei polymerase chain reaction result. Cerebral magnetic resonance imaging revealed a typical pattern of limbic encephalitis with an intense signal in the amygdalae and hippocampi. The outcome under antibiotic treatment was marked by partial improvement of the cognitive disorders, disappearance of the positive T whipplei polymerase chain reaction result in cerebrospinal fluid, and a clear decrease of inflammation on brain magnetic resonance imaging. CONCLUSIONS: Whipple disease can present as limbic encephalitis. Few cases have been previously described in the literature. Such diagnosis is of importance because of the specific treatment. PMID- 22084134 TI - Ring sign on diffusion-weighted imaging. PMID- 22084135 TI - Pontine ring-enhancing glioblastoma multiforme-like fungal abscess. PMID- 22084136 TI - Unilateral tongue atrophy and fasciculation. PMID- 22084137 TI - Limitations of NIS database in evaluation of epilepsy surgery morbidity and mortality. PMID- 22084138 TI - The European Society of Cardiology publishes its first Guidelines on peripheral artery diseases. PMID- 22084140 TI - Remembrances of Walter M. Fitch. PMID- 22084141 TI - BRIEF: Computing a Local Binary Descriptor Very Fast. AB - Binary descriptors are becoming increasingly popular as a means to compare feature points very fast while requiring comparatively small amounts of memory. The typical approach to creating them is to first compute floating-point ones, using an algorithm such as SIFT, and then to binarize them. In this paper, we show that we can directly compute a binary descriptor, which we call BRIEF, on the basis of simple intensity difference tests. As a result, BRIEF is very fast both to build and to match. We compare it against SURF and SIFT on standard benchmarks and show that it yields comparable recognition accuracy, while running in an almost vanishing fraction of the time required by either. PMID- 22084142 TI - Combining Single and Packet-Ray Tracing for Arbitrary Ray Distributions on the Intel MIC Architecture. AB - Wide-SIMD hardware is power and area efficient, but it is challenging to efficiently map ray tracing algorithms to such hardware especially when the rays are incoherent. The two most commonly used schemes are either packet tracing, or relying on a separate traversal stack for each SIMD lane. Both work great for coherent rays, but suffer when rays are incoherent: The former experiences a dramatic loss of SIMD utilization once rays diverge; the latter requires a large local storage, and generates multiple incoherent streams of memory accesses that present challenges for the memory system. In this paper, we introduce a single ray tracing scheme for incoherent rays that uses just one traversal stack on 16 wide SIMD hardware. It uses a bounding-volume hierarchy with a branching factor of four as the acceleration structure, exploits four-wide SIMD in each box and primitive intersection test, and uses 16-wide SIMD by always performing four such node or primitive tests in parallel. We then extend this scheme to a hybrid tracing scheme that automatically adapts to varying ray coherence by starting out with a 16-wide packet scheme and switching to the new single-ray scheme as soon as rays diverge. We show that on the Intel Many Integrated Core architecture this hybrid scheme consistently, and over a wide range of scenes and ray distributions, outperforms both packet and single-ray tracing. PMID- 22084143 TI - A Curvature-Adaptive Implicit Surface Reconstruction for Irregularly Spaced Points. AB - A curvature-adaptive implicit surface reconstruction for noisy and irregularly spaced points in 3D is introduced. The reconstructed surface traces the zero crossings of a signed field obtained from the sum of first-derivative anisotropic Gaussians centered at the points. The standard deviations of the anisotropic Gaussians are adapted to surface curvatures estimated from local data. A key characteristic of the formulation is its ability to smooth more along edges than across them, thereby preserving shape details while smoothing noise. The behavior of the proposed method under various density and organization of points is investigated and surface reconstruction results are compared with those obtained by well-known methods in the literature. PMID- 22084144 TI - Tuning self-motion perception in virtual reality with visual illusions. AB - Motion perception in immersive virtual environments significantly differs from the real world. For example, previous work has shown that users tend to underestimate travel distances in virtual environments (VEs). As a solution to this problem, researchers proposed to scale the mapped virtual camera motion relative to the tracked real-world movement of a user until real and virtual motion are perceived as equal, i.e., real-world movements could be mapped with a larger gain to the VE in order to compensate for the underestimation. However, introducing discrepancies between real and virtual motion can become a problem, in particular, due to misalignments of both worlds and distorted space cognition. In this paper, we describe a different approach that introduces apparent self motion illusions by manipulating optic flow fields during movements in VEs. These manipulations can affect self-motion perception in VEs, but omit a quantitative discrepancy between real and virtual motions. In particular, we consider to which regions of the virtual view these apparent self-motion illusions can be applied, i.e., the ground plane or peripheral vision. Therefore, we introduce four illusions and show in experiments that optic flow manipulation can significantly affect users' self-motion judgments. Furthermore, we show that with such manipulations of optic flow fields the underestimation of travel distances can be compensated. PMID- 22084145 TI - Designing filters for fast-known NcRNA identification. AB - Detecting members of known noncoding RNA (ncRNA) families in genomic DNA is an important part of sequence annotation. However, the most widely used tool for modeling ncRNA families, the covariance model (CM), incurs a high-computational cost when used for genome-wide search. This cost can be reduced by using a filter to exclude sequences that are unlikely to contain the ncRNA of interest, applying the CM only where it is likely to match strongly. Despite recent advances, designing an efficient filter that can detect ncRNA instances lacking strong conservation while excluding most irrelevant sequences remains challenging. In this work, we design three types of filters based on multiple secondary structure profiles (SSPs). An SSP augments a regular profile (i.e., a position weight matrix) with secondary structure information but can still be efficiently scanned against long sequences. Multi-SSPbased filters combine evidence from multiple SSP matches and can achieve high sensitivity and specificity. Our SSP-based filters are extensively tested in BRAliBase III data set, Rfam 9.0, and a published soil metagenomic data set. In addition, we compare the SSPbased filters with several other ncRNA search tools including Infernal (with profile HMMs as filters), ERPIN, and tRNAscan-SE. Our experiments demonstrate that carefully designed SSP filters can achieve significant speedup over unfiltered CM search while maintaining high sensitivity for various ncRNA families. The designed filters and filter-scanning programs are available at our website: www.cse.msu.edu/~yannisun/ssp/. PMID- 22084146 TI - Eigen-genomic system dynamic-pattern analysis (ESDA): modeling mRNA degradation and self-regulation. AB - High-throughput methods systematically measure the internal state of the entire cell, but powerful computational tools are needed to infer dynamics from their raw data. Therefore, we have developed a new computational method, Eigen-genomic System Dynamic-pattern Analysis (ESDA), which uses systems theory to infer dynamic parameters from a time series of gene expression measurements. As many genes are measured at a modest number of time points, estimation of the system matrix is underdetermined and traditional approaches for estimating dynamic parameters are ineffective; thus, ESDA uses the principle of dimensionality reduction to overcome the data imbalance. Since degradation rates are naturally confounded by self-regulation, our model estimates an effective degradation rate that is the difference between self-regulation and degradation. We demonstrate that ESDA is able to recover effective degradation rates with reasonable accuracy in simulation. We also apply ESDA to a budding yeast dataset, and find that effective degradation rates are normally slower than experimentally measured degradation rates. Our results suggest that either self-regulation is widespread in budding yeast and that self-promotion dominates self-inhibition, or that self regulation may be rare and that experimental methods for measuring degradation rates based on transcription arrest may severely overestimate true degradation rates in healthy cells. PMID- 22084147 TI - Identification of essential proteins based on edge clustering coefficient. AB - Identification of essential proteins is key to understanding the minimal requirements for cellular life and important for drug design. The rapid increase of available protein-protein interaction (PPI) data has made it possible to detect protein essentiality on network level. A series of centrality measures have been proposed to discover essential proteins based on network topology. However, most of them tended to focus only on the location of single protein, but ignored the relevance between interactions and protein essentiality. In this paper, a new centrality measure for identifying essential proteins based on edge clustering coefficient, named as NC, is proposed. Different from previous centrality measures, NC considers both the centrality of a node and the relationship between it and its neighbors. For each interaction in the network, we calculate its edge clustering coefficient. A node's essentiality is determined by the sum of the edge clustering coefficients of interactions connecting it and its neighbors. The new centrality measure NC takes into account the modular nature of protein essentiality. NC is applied to three different types of yeast protein-protein interaction networks, which are obtained from the DIP database, the MIPS database and the BioGRID database, respectively. The experimental results on the three different networks show that the number of essential proteins discovered by NC universally exceeds that discovered by the six other centrality measures: DC, BC, CC, SC, EC, and IC. Moreover, the essential proteins discovered by NC show significant cluster effect. PMID- 22084148 TI - A framework for incorporating functional interrelationships into protein function prediction algorithms. AB - The functional annotation of proteins is one of the most important tasks in the post-genomic era. Although many computational approaches have been developed in recent years to predict protein function, most of these traditional algorithms do not take interrelationships among functional terms into account, such as different GO terms usually coannotate with some common proteins. In this study, we propose a new functional similarity measure in the form of Jaccard coefficient to quantify these interrelationships and also develop a framework for incorporating GO term similarity into protein function prediction process. The experimental results of cross-validation on S. cerevisiae and Homo sapiens data sets demonstrate that our method is able to improve the performance of protein function prediction. In addition, we find that small size terms associated with a few of proteins obtain more benefit than the large size ones when considering functional interrelationships. We also compare our similarity measure with other two widely used measures, and results indicate that when incorporated into function prediction algorithms, our proposed measure is more effective. Experiment results also illustrate that our algorithms outperform two previous competing algorithms, which also take functional interrelationships into account, in prediction accuracy. Finally, we show that our method is robust to annotations in the database which are not complete at present. These results give new insights about the importance of functional interrelationships in protein function prediction. PMID- 22084149 TI - A top-r feature selection algorithm for microarray gene expression data. AB - Most of the conventional feature selection algorithms have a drawback whereby a weakly ranked gene that could perform well in terms of classification accuracy with an appropriate subset of genes will be left out of the selection. Considering this shortcoming, we propose a feature selection algorithm in gene expression data analysis of sample classifications. The proposed algorithm first divides genes into subsets, the sizes of which are relatively small (roughly of size h), then selects informative smaller subsets of genes (of size r < h) from a subset and merges the chosen genes with another gene subset (of size r) to update the gene subset. We repeat this process until all subsets are merged into one informative subset. We illustrate the effectiveness of the proposed algorithm by analyzing three distinct gene expression data sets. Our method shows promising classification accuracy for all the test data sets. We also show the relevance of the selected genes in terms of their biological functions. PMID- 22084150 TI - A new efficient data structure for storage and retrieval of multiple biosequences. AB - Today's genome analysis applications require sequence representations allowing for fast access to their contents while also being memory-efficient enough to facilitate analyses of large-scale data. While a wide variety of sequence representations exist, lack of a generic implementation of efficient sequence storage has led to a plethora of poorly reusable or programming language-specific implementations. We present a novel, space-efficient data structure (GtEncseq) for storing multiple biological sequences of variable alphabet size, with customizable character transformations, wildcard support and an assortment of internal representations optimized for different distributions of wildcards and sequence lengths. For the human genome (3.1 gigabases, including 237 million wildcard characters) our representation requires only 2 + 8 × 10^-6bits per character. Implemented in C, our portable software implementation provides a variety of methods for random and sequential access to characters and substrings (including different reading directions) using an object-oriented interface. In addition, it includes access to metadata like sequence descriptions or character distributions. The library is extensible to be used from various scripting languages. GtEncseq is much more versatile than previous solutions, adding features that were previously unavailable. Benchmarks show that it is competitive with respect to space and time requirements. PMID- 22084151 TI - Low-dose Erythropoietin reduces risk of heart failure induced by anti-cancer therapy. PMID- 22084152 TI - Microsatellite instability in colorectal cancer: time to stop hiding! PMID- 22084153 TI - Impact of phosphodiesterase 8B gene rs4704397 variation on thyroid homeostasis in childhood obesity. AB - CONTEXT: Several studies demonstrated that obese children have higher TSH than normal-weight children. The polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene showed an association with TSH. OBJECTIVES: i) To assess the effect of PDE8B on TSH in obese children; ii) to dissect the role of obesity degree in modulating this association; and iii) to stratify the individual risk to show hyperthyrotropinaemia according to PDE8B genotype. METHODS: Eight hundred and sixty-seven Italian obese children were investigated. Clinical data and thyroid hormones were evaluated and the PDE8B rs4704397 was genotyped. RESULTS: PDE8B A/A homozygous subjects showed higher TSH (P=0.0005) compared with A/G or G/G. No differences were found for peripheral thyroid hormones. Among A/A children, 22% had hyperthyrotropinaemia, compared with 11.6% of heterozygotes and 10.8% of G/G (P=0.0008). Consistently, A/A had an odds ratio (OR) to show abnormal TSH level of 2.25 (P=0.0004). Body mass index (BMI) appeared correlated with TSH (P=0.0001), but the strength of the effect of PDE8B on TSH was independent of BMI (P=0.1). Children were subdivided into six groups according to obesity degree and genotypes. PDE8B A/A with BMI SDS above 3 had the highest OR (OR 2.6, P=0.0015) to have hyperthyrotropinaemia, whereas G/G with BMI SDS below 3 showed the lowest possibilities (OR 0.3, P=0.005). CONCLUSIONS: We have shown: i) in obese children, PDE8B is associated with TSH; ii) the interaction between adiposity and PDE8B on TSH is not synergistic, but follows an additive model; and iii) impact of this association in the stratification of individual risk to have hyperthyrotropinaemia. PMID- 22084154 TI - Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation. AB - Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases. PMID- 22084155 TI - Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d'etude des Tumeurs Endocrines database. AB - OBJECTIVE: Limited data regarding adrenal involvement in multiple endocrine neoplasia type 1 (MEN1) is available. We describe the characteristics of MEN1 associated adrenal lesions in a large cohort to provide a rationale for their management. METHODS: Analysis of records from 715 MEN1 patients from a multicentre database between 1956 and 2008. Adrenal lesions were compared with those from a multicentre cohort of 144 patients with adrenal sporadic incidentalomas. RESULTS: Adrenal enlargement was reported in 20.4% (146/715) of patients. Adrenal tumours (>10 mm in size) accounted for 58.1% of these cases (10.1% of the whole patient cohort). Tumours were bilateral and >40 mm in size in 12.5 and 19.4% of cases respectively. Hormonal hypersecretion was restricted to patients with tumours and occurred in 15.3% of them. Compared with incidentalomas, MEN1-related tumours exhibited more cases of primary hyperaldosteronism, fewer pheochromocytomas and more adrenocortical carcinomas (ACCs; 13.8 vs 1.3%). Ten ACCs occurred in eight patients. Interestingly, ACCs occurred after several years of follow-up of small adrenal tumours in two of the eight affected patients. Nine of the ten ACCs were classified as stage I or II according to the European Network for the Study of Adrenal Tumors. No evident genotype/phenotype correlation was found for the occurrence of adrenal lesions, endocrine hypersecretion or ACC. CONCLUSIONS: Adrenal pathology in MEN1 differs from that observed in sporadic incidentalomas. In the absence of relevant symptoms, endocrine biology can be restricted to patients with adrenal tumours and should focus on steroid secretion including the aldosterone-renin system. MEN1 is a high-risk condition for the occurrence of ACCs. It should be considered regardless of the size of the tumour. PMID- 22084156 TI - The utility of basal serum LH in prediction of central precocious puberty in girls. AB - OBJECTIVE: The mainstay of distinction between prepubertal girls and girls who are suspected of having central precocious puberty (CPP) is based on gonadotropin measurements after a GnRH stimulation test to evaluate hypothalamic-pituitary gonadal axis maturity. The objective of this study was to determine whether a single basal gonadotropin measurement carries a useful predictive value in verifying or refuting the diagnosis of CPP. DESIGN AND METHODS: Basal serum LH and FSH were measured by a chemiluminescent immunometric assay in a cohort of girls who had been evaluated for CPP before and after GnRH stimulation test. Peak LH levels higher than 5 IU/l were considered a pubertal response. RESULTS: Eighty girls with suspected breast development before 8 years of age were enrolled to the study, out of whom 42 had CPP. Low basal serum LH (<=0.1 IU/l) was sufficient to rule out the diagnosis of CPP in 94.7% of the 38 prepubertal girls; the sensitivity of basal LH levels for this purpose was only 64%. The basal FSH and the basal LH to FSH ratio achieved less efficient predictive value with 76 and 71% sensitivity and 73 and 86% specificity respectively. CONCLUSION: A single basal LH measurement may be adequate to confirm but not to refute the presence of CPP in most of the girls who are evaluated for early pubertal signs. PMID- 22084158 TI - Three-dimensional distribution of the vitelliform lesion, photoreceptors, and retinal pigment epithelium in the macula of patients with best vitelliform macular dystrophy. AB - OBJECTIVE: To describe the anatomical phenotypes of Best vitelliform macular dystrophy (BVMD) with spectral-domain optical coherence tomography (SD-OCT) in a large series of patients with confirmed mutations in the BEST1 gene. METHODS: In our retrospective observational case series, we assessed 15 patients (30 eyes) with a clinical diagnosis of vitelliform macular dystrophy who were found to have mutations in the BEST1 gene. Color fundus photographs and SD-OCT images were evaluated and compared with those of 15 age-matched controls (30 eyes). Using a validated 3-dimensional SD-OCT segmentation algorithm, we calculated the equivalent thickness of photoreceptors and the equivalent thickness of the retinal pigment epithelium for each patient. The photoreceptor equivalent thickness and the retinal pigment epithelium (RPE) equivalent thickness were compared in all patients, in a region of the macula outside the central lesion for patients with BVMD and outside the fovea in control patients. Paired t tests were used for statistical analysis. RESULTS: The SD-OCT findings revealed that the vitelliform lesion consists of material above the RPE and below the outer segment tips. Additionally, drusen-like deposition of sub-RPE material was notable, and several patients exhibited a sub-RPE fibrotic nodule. Patients with BVMD had a mean photoreceptor equivalent thickness of 28.3 MUm, and control patients had a mean photoreceptor equivalent thickness of 21.8 MUm, a mean difference of 6.5 MUm (P < .01), whereas the mean RPE equivalent thickness was not statistically different between patients with BVMD and control patients (P = .53). CONCLUSIONS: The SD-OCT findings suggest that vitelliform material is located in the subretinal space and that BVMD is associated with diffuse photoreceptor outer segment abnormalities overlying a structurally normal RPE. CLINICAL RELEVANCE: These findings provide new insight into the pathophysiology of BVMD and thus have implications for the development of therapeutic interventions. PMID- 22084157 TI - Glaucoma-related adverse events in the Infant Aphakia Treatment Study: 1-year results. AB - OBJECTIVES: To report the incidence of glaucoma and glaucoma suspects in the IATS, and to evaluate risk factors for the development of a glaucoma-related adverse event in patients in the IATS in the first year of follow-up. METHODS: A total of 114 infants between 1 and 6 months of age with a unilateral congenital cataract were assigned to undergo cataract surgery either with or without an intraocular lens implant. Standardized definitions of glaucoma and glaucoma suspect were created and used in the IATS. RESULTS: Of these 114 patients, 10 (9%) developed glaucoma and 4 (4%) had glaucoma suspect, for a total of 14 patients (12%) with a glaucoma-related adverse event in the treated eye through the first year of follow-up. Of the 57 patients who underwent lensectomy and anterior vitrectomy, 5 (9%) developed a glaucoma-related adverse event; of the 57 patients who underwent an intraocular lens implant, 9 (16%) developed a glaucoma related adverse event. The odds of developing a glaucoma-related adverse event were 3.1 times higher for a child with persistent fetal vasculature and 1.6 times higher for each month of age younger at cataract surgery. CONCLUSIONS: Modern surgical techniques do not eliminate the early development of glaucoma following congenital cataract surgery with or without an intraocular lens implant. Younger patients with or without persistent fetal vasculature seem more likely to develop a glaucoma-related adverse event in the first year of follow-up. Vigilance for the early development of glaucoma is needed following congenital cataract surgery, especially when surgery is performed during early infancy or for a child with persistent fetal vasculature. Five-year follow-up data for the IATS will likely reveal more glaucoma-related adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00212134. PMID- 22084160 TI - Prevention and management of graft detachment in descemet membrane endothelial keratoplasty. AB - OBJECTIVE: To describe the prevention and management of various types of graft detachment after Descemet membrane endothelial keratoplasty. METHODS: In 150 consecutive eyes that underwent Descemet membrane endothelial keratoplasty, the incidence and type of graft detachment were studied at 1, 3, 6, 9, 12, and 24 months after surgery in a nonrandomized, prospective clinical study at a tertiary referral center. Four groups of detachments were identified: a partial detachment of one-third or less of the graft surface area (n = 16; group 1); a partial detachment of more than one-third of the graft surface area (n = 8; group 2); a graft positioned upside down (n = 4; group 3); and a free-floating Descemet roll in the host anterior chamber (n = 8; group 4). RESULTS: Partial or complete graft detachment was found in 36 cases (24%), of which 18 (12%) were clinically significant. All 24 eyes with a partial detachment (groups 1 and 2) showed spontaneous corneal clearance, and all but 6 of these eyes (75%) reached visual acuity of 20/40 or better (>=0.5). A reversed clearance pattern and interface spikes were observed in eyes with the graft positioned upside down (group 3). Eyes with a free-floating graft (group 4) showed persistent corneal edema. Detachments were associated with inward folds (12 eyes [33%]), insufficient air bubble support (7 eyes [19%]), upside-down graft positioning (4 eyes [11%]), use of plastic materials (2 eyes [6%]), irido-graft synechiae (1 eye [3%]), poor endothelial morphology (1 eye [3%]), and stromal irregularity under the main incision (1 eye [3%]); 14 (58%) of the partial detachments were localized inferiorly. CONCLUSIONS: Awaiting spontaneous clearance may be advocated in eyes with a partial detachment. Minor adjustments in surgical protocol as well as careful patient selection may further reduce the incidence of graft detachment after Descemet membrane endothelial keratoplasty to 4% or less. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00521898. PMID- 22084159 TI - Retinal microvascular signs and disability in the Cardiovascular Health Study. AB - OBJECTIVE: To study the associations of retinal microvascular changes, which are associated with systemic conditions and cognitive decline, with disability in performing activities of daily living (ADL). DESIGN: Prospective cohort study of 1487 community-dwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as self-reported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction. RESULTS: During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1% vs 7.1%; adjusted hazard ratio, 1.45; 95% confidence interval, 1.24-1.69; P < .001). There was no evidence of interaction by advanced carotid atherosclerosis (P > .10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging. CONCLUSIONS: These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction. PMID- 22084162 TI - Genomic c-Myc quadruplex DNA selectively kills leukemia. AB - c-Myc, a key regulator of cell cycle and proliferation, is commonly overexpressed in leukemia and associated with poor prognosis. Conventional antisense oligonucleotides targeting c-myc may attenuate leukemic cell growth, however, are poorly taken into cells, rapidly degraded, and have unwanted effects on normal cells. The c-myc promoter contains a guanine-rich sequence (PU27) capable of forming quadruplex (four-stranded) DNA, which may negatively regulate c-myc transcription. However, its biological significance is unknown. We show that treatment of leukemia with an oligonucleotide encoding the genomic PU27 sequence induces cell-cycle arrest and death by oncotic necrosis due to PU27-mediated suppression of c-myc mRNA/protein expression. Furthermore, PU27 is abundantly taken into cells, localized in the cytoplasm/nucleus, inherently stable in serum and intracellularly, and has no effect on normal cells. Suppression of c-myc expression by PU27 caused significant DNA damage, cell and mitochondrial swelling, and membrane permeability characteristic of oncotic necrosis. Induction of oncosis caused mitochondrial dysfunction, depletion of cellular ATP levels, and enhanced oxidative stress. This novel antileukemic strategy addresses current concerns of oligonucleotide therapeutics including problems with uptake, stability, and unintentional effects on normal cells and is the first report of selective cancer cell killing by a genomic DNA sequence. PMID- 22084163 TI - Effective targeting of Hedgehog signaling in a medulloblastoma model with PF 5274857, a potent and selective Smoothened antagonist that penetrates the blood brain barrier. AB - Inhibition of the Smoothened (Smo) represents a promising therapeutic strategy for treating malignant tumors that are dependent on the Hedgehog (Hh) signaling pathway. PF-5274857 is a novel Smo antagonist that specifically binds to Smo with a K(i) of 4.6 +/- 1.1 nmol/L and completely blocks the transcriptional activity of the downstream gene Gli1 with an IC(50) of 2.7 +/- 1.4 nmol/L in cells. This Smo antagonist showed robust antitumor activity in a mouse model of medulloblastoma with an in vivo IC(50) of 8.9 +/- 2.6 nmol/L. The downregulation of Gli1 is closely linked to the tumor growth inhibition in patched(+/-) medulloblastoma mice. Mathematical analysis of the relationship between the drug's pharmacokinetics and Gli1 pharmacodynamics in patched(+/-) medulloblastoma tumor models yielded similar tumor and skin Gli1 IC(50) values, suggesting that skin can be used as a surrogate tissue for the measurement of tumor Gli1 levels. In addition, PF-5274857 was found to effectively penetrate the blood-brain barrier and inhibit Smo activity in the brain of primary medulloblastoma mice, resulting in improved animal survival rates. The brain permeability of PF-5274857 was also confirmed and quantified in nontumor-bearing preclinical species with an intact blood-brain barrier. PF-5274857 was orally available and metabolically stable in vivo. These findings suggest that PF-5274857 is a potentially attractive clinical candidate for the treatment of tumor types including brain tumors and brain metastasis driven by an activated Hh pathway. PMID- 22084164 TI - Vascular disruption in combination with mTOR inhibition in renal cell carcinoma. AB - Renal cell carcinoma (RCC) is an angiogenesis-dependent and hypoxia-driven malignancy. As a result, there has been an increased interest in the use of antiangiogenic agents for the management of RCC in patients. However, the activity of tumor-vascular disrupting agents (tumor-VDA) has not been extensively examined against RCC. In this study, we investigated the therapeutic efficacy of the tumor-VDA ASA404 (DMXAA, 5,6-dimethylxanthenone-4-acetic acid, or vadimezan) in combination with the mTOR inhibitor everolimus (RAD001) against RCC. In vitro studies were carried out using human umbilical vein endothelial cells and in vivo studies using orthotopic RENCA tumors and immunohistochemical patient tumor derived RCC xenografts. MRI was used to characterize the vascular response of orthotopic RENCA xenografts to combination treatment. Therapeutic efficacy was determined by tumor growth measurements and histopathologic evaluation. ASA404/everolimus combination resulted in enhanced inhibition of endothelial cell sprouting in the 3-dimensional spheroid assay. MRI of orthotopic RENCA xenografts revealed an early increase in permeability 4 hours posttreatment with ASA404, but not with everolimus. Twenty-four hours after treatment, a significant reduction in blood volume was observed with combination treatment. Correlative CD31/NG2 staining of tumor sections confirmed marked vascular damage following combination therapy. Histologic sections showed extensive necrosis and a reduction in the viable rim following combination treatment compared with VDA treatment alone. These results show the potential of combining tumor-VDAs with mTOR inhibitors in RCC. Further investigation into this novel combination strategy is warranted. PMID- 22084165 TI - Targeting interleukin-4 receptor alpha with hybrid peptide for effective cancer therapy. AB - Interleukin-4 receptor alpha (IL-4Ralpha) chain is highly expressed on the surface of various human solid tumors. We designed a novel hybrid peptide termed IL-4Ralpha-lytic peptide that targets the IL-4Ralpha chain. The IL-4Ralpha-lytic peptide contains a target moiety to bind to IL-4Ralpha and a cellular toxic lytic peptide that selectively kills cancer cells. The anticancer activity of the IL 4Ralpha-lytic peptide was evaluated in vitro and in vivo. It was found that the IL-4Ralpha-lytic peptide has cytotoxic activity in cancer cell lines expressing IL-4Ralpha, determined by quantitative real-time PCR. The IC(50) ratios of the lytic peptide to the IL-4Ralpha-lytic peptide correlated well with the expression levels of IL-4Ralpha on cancer cells (r = 0.80). In addition, IL-4Ralpha-lytic peptide administered either intratumoraly or intravenously significantly inhibited tumor growth in xenograft model of human pancreatic cancer (BXPC-3) in mice. These results indicate that the IL-4Ralpha-lytic peptide generated in this study has a potent and selective anticancer potential against IL-4Ralpha-positive solid cancers. PMID- 22084166 TI - Induction of vascular endothelial growth factor secretion by childhood acute lymphoblastic leukemia cells via the FLT-3 signaling pathway. AB - Human leukemia cells secrete VEGF, which can act in a paracrine manner within the bone marrow microenvironment to promote leukemia cell survival and proliferation. The FLT-3 receptor tyrosine kinase plays an essential role in regulating normal hematopoiesis, but its constitutive activation via mutation in acute leukemias is generally associated with poor outcome. The aim of this study was to investigate interactions between the FLT-3 and VEGF signaling pathways in acute leukemia using cell lines and ex vivo cultures of pediatric acute lymphoblastic leukemia cells following expansion of direct patient explants in immunodeficient mice. Different xenograft lines exhibited variable cell surface FLT-3 expression, as well as basal and FLT-3 ligand-induced VEGF secretion, whereas the MV4;11 cell line, which expresses constitutively active FLT-3, secreted high levels of VEGF. The FLT-3 inhibitor, SU11657, significantly reduced VEGF secretion in three of six xenograft lines and MV4;11 cells, in conjunction with inhibition of FLT-3 tyrosine phosphorylation. Moreover, exposure of xenograft cells to the FLT-3 blocking antibody, D43, also reduced VEGF secretion to basal levels and decreased FLT-3 tyrosine phosphorylation. In terms of downstream signaling, SU11657 and D43 both caused dephosphorylation of extracellular signal-regulated kinase 1/2, with no changes in AKT or STAT5 phosphorylation. Finally, partial knockdown of FLT-3 expression by short interfering RNA also resulted in inhibition of VEGF secretion. These results indicate that FLT-3 signaling plays a central role in the regulation of VEGF secretion and that inhibition of the FLT-3/VEGF pathway may disrupt paracrine signaling between leukemia cells and the bone marrow microenvironment. PMID- 22084167 TI - Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo. AB - In this study, we investigated the functional role of Akt and c-jun-NH(2)-kinase (JNK) signaling cascades in apigenin-induced apoptosis in U937 human leukemia cells and anti-leukemic activity of apigenin in vivo. Apigenin induced apoptosis by inactivation of Akt with a concomitant activation of JNK, Mcl-1 and Bcl-2 downregulation, cytochrome c release from mitochondria, and activation of caspases. Constitutively active myristolated Akt prevented apigenin-induced JNK, caspase activation, and apoptosis. Conversely, LY294002 and a dominant-negative construct of Akt potentiated apigenin-induced apoptosis in leukemia cells. Interruption of the JNK pathway showed marked reduction in apigenin-induced caspase activation and apoptosis in leukemia cells. Furthermore, in vivo administration of apigenin resulted in attenuation of tumor growth in U937 xenografts accompanied by inactivation of Akt and activation of JNK. Attenuation of tumor growth in U937 xenografts by apigenin raises the possibility that apigenin may have clinical implications and can be further tested for incorporating in leukemia treatment regimens. PMID- 22084168 TI - Gene expression profile in response to doxorubicin-rapamycin combined treatment of HER-2-overexpressing human mammary epithelial cell lines. AB - HER-2-positive breast cancers frequently sustain elevated AKT/mTOR signaling, which has been associated with resistance to doxorubicin treatment. Here, we investigated whether rapamycin, an mTOR inhibitor, increased the sensitivity to doxorubicin therapy in two HER-2-overexpressing cell lines: C5.2, which was derived from the parental HB4a by transfection with HER-2 and SKBR3, which exhibits HER-2 amplification. The epithelial mammary cell line HB4a was also analyzed. The combined treatment using 20 nmol/L of rapamycin and 30 nmol/L of doxorubicin arrested HB4a and C5.2 cells in S to G(2)-M, whereas SKBR3 cells showed an increase in the G(0)-G(1) phase. Rapamycin increased the sensitivity to doxorubicin in HER-2-overexpressing cells by approximately 2-fold, suggesting that the combination displayed a more effective antiproliferative action. Gene expression profiling showed that these results might reflect alterations in genes involved in canonical pathways related to purine metabolism, oxidative phosphorylation, protein ubiquitination, and mitochondrial dysfunction. A set of 122 genes modulated by the combined treatment and specifically related to HER-2 overexpression was determined by finding genes commonly regulated in both C5.2 and SKBR3 that were not affected in HB4a cells. Network analysis of this particular set showed a smaller subgroup of genes in which coexpression pattern in HB4a cells was disrupted in C5.2 and SKBR3. Altogether, our data showed a subset of genes that might be more robust than individual markers in predicting the response of HER-2-overexpressing breast cancers to doxorubicin and rapamycin combination. PMID- 22084171 TI - Targeting allosteric regulatory modules in oncoproteins: "drugging the undruggable". PMID- 22084169 TI - Targeted mutations in the ATR pathway define agent-specific requirements for cancer cell growth and survival. AB - Many anticancer agents induce DNA strand breaks or cause the accumulation of DNA replication intermediates. The protein encoded by ataxia-telangiectasia mutated and Rad 3-related (ATR) generates signals in response to these altered DNA structures and activates cellular survival responses. Accordingly, ATR has drawn increased attention as a potential target for novel therapeutic strategies designed to potentiate the effects of existing drugs. In this study, we use a unique panel of genetically modified human cancer cells to unambiguously test the roles of upstream and downstream components of the ATR pathway in the responses to common therapeutic agents. Upstream, the S-phase-specific cyclin-dependent kinase (Cdk) 2 was required for robust activation of ATR in response to diverse chemotherapeutic agents. While Cdk2-mediated ATR activation promoted cell survival after treatment with many drugs, signaling from ATR directly to the checkpoint kinase Chk1 was required for survival responses to only a subset of the drugs tested. These results show that specifically inhibiting the Cdk2/ATR/Chk1 pathway via distinct regulators can differentially sensitize cancer cells to a wide range of therapeutic agents. PMID- 22084174 TI - Role of imaging in the diagnosis, staging, and treatment of thymoma. AB - Thymoma is a rare mediastinal neoplasm but is the most common primary neoplasm of the anterior mediastinum. There have been only a few published reports assessing this disease. Furthermore, many of these reports are from a single institution and span several decades, which may lead to potentially misleading conclusions related to diagnosis, staging, and treatment. Computed tomography is the imaging modality of choice for evaluating thymoma and can help distinguish thymoma from other anterior mediastinal abnormalities. Tumor stage and extent of resection are the most important prognostic factors. Tumors that are encapsulated and are amenable to complete resection have a good prognosis, whereas invasive and unresectable tumors have a poor prognosis regardless of their histologic characteristics. Radiologists must be aware of the full spectrum of imaging findings of thymoma, the standard guidelines for diagnostic evaluation, and how imaging findings affect therapeutic decisions. PMID- 22084170 TI - MK1775, a selective Wee1 inhibitor, shows single-agent antitumor activity against sarcoma cells. AB - Wee1 is a critical component of the G(2)-M cell-cycle checkpoint control and mediates cell-cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by a selective small molecule inhibitor MK1775 can abrogate G(2)-M checkpoint, resulting in premature mitotic entry and cell death. MK1775 has recently been tested in preclinical and clinical studies of human carcinoma to enhance the cytotoxic effect of DNA-damaging agents. However, its role in mesenchymal tumors, especially as a single agent, has not been explored. Here, we studied the cytotoxic effect of MK1775 in various sarcoma cell lines and patient derived tumor explants ex vivo. Our data show that MK1775 treatment at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death in all sarcomas tested. In MK1775-treated cells, CDC2 activity was enhanced, as determined by decreased inhibitory phosphorylation of tyrosine-15 residue and increased expression of phosphorylated histone H3, a marker of mitotic entry. The cytotoxic effect of Wee1 inhibition on sarcoma cells seems to be independent of p53 status as all sarcoma cell lines with different p53 mutation were highly sensitive to MK1775 treatment. Finally, in patient derived sarcoma samples, we showed that MK1775 as a single agent causes significant apoptotic cell death, suggesting that Wee1 inhibition may represent a novel approach in the treatment of sarcomas. PMID- 22084176 TI - Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. AB - Sclerosing bone dysplasias are skeletal abnormalities of varying severity with a wide range of radiologic, clinical, and genetic features. Hereditary sclerosing bone dysplasias result from some disturbance in the pathways involved in osteoblast or osteoclast regulation, leading to abnormal accumulation of bone. Several genes have been discovered that, when disrupted, result in specific types of hereditary sclerosing bone dysplasia (osteopetrosis, pyknodysostosis, osteopoikilosis, osteopathia striata, progressive diaphyseal dysplasia, hereditary multiple diaphyseal sclerosis, hyperostosis corticalis generalisata), many of which exhibit similar pathologic mechanisms involving endochondral or intramembranous ossification and some of which share similar underlying genetic defects. Nonhereditary dysplasias include intramedullary osteosclerosis, melorheostosis, and overlap syndromes, whereas acquired syndromes with increased bone density, which may simulate sclerosing bone dysplasias, include osteoblastic metastases, Paget disease of bone, Erdheim-Chester disease, myelofibrosis, and sickle cell disease. Knowledge of the radiologic appearances, distribution, and associated clinical findings of hereditary and nonhereditary sclerosing bone dysplasias and acquired syndromes with increased bone density is crucial for accurate diagnosis. PMID- 22084177 TI - AIRP best cases in radiologic-pathologic correlation: synovial chondrosarcoma. PMID- 22084178 TI - Masses and malformations of the third ventricle: normal anatomic relationships and differential diagnoses. AB - The third ventricle lies in the center of the brain. It is surrounded by critical nuclear structures (the hypothalamus and thalami) and important glandular structures (the pituitary and pineal glands). Although a wide array of pathologic processes may involve the third ventricle, most are extrinsic masses. By understanding the anatomic boundaries of the third ventricle and its relationship to adjacent structures, it is possible to create short lists of differential diagnoses. Third ventricle masses can be classified as arising in or immediately adjacent to one of five locations: anterior, posterior, inferior, foramen of Monro, and intraventricular. Anterior masses involve the optic and infundibular recesses, posterior masses affect or arise in the posterior commissure and pineal gland, and inferior masses involve or affect the ventricle floor. Masses may also arise at or adjacent to the foramen of Monro or entirely within the third ventricle. Of the intraventricular masses, chordoid glioma-a rare low-grade primary neoplasm-is unique to the third ventricle. Congenital malformations of the third ventricle are uncommon and are most often noted during childhood. Most commonly, these anomalies represent malformations of the neurohypophysis, which may manifest as hormonal abnormalities, or stenosis of the aqueduct of Sylvius, which manifests as dilatation of the third and lateral ventricles (hydrocephalus). PMID- 22084179 TI - Primary lesions of the root of the tongue. AB - In the assessment of the head and neck, differential diagnoses can be formulated by subdividing the anatomy into spaces along identifiable and logical boundaries. In the oral cavity, the root of the tongue is notably unlike adjacent regions due to structural and tissue-specific differences. The majority of lesions found in the root of the tongue are congenital and benign, representing ectopic tissues of thyroidal, epidermal, dermal, foregut, venous, and lymphatic origin. A greater number of acquired neoplasms and infections are seen in the adjacent sublingual, submandibular, and oropharyngeal regions of the base of the tongue, presumably due to their greater exposure to mucosal surfaces and lymphatic tissues. Many lesions of the root of the tongue have clinical and imaging characteristics that can help narrow the differential diagnosis, and surgical management may be required. Familiarity with these lesions and how they differ from other lesions of the oral cavity and oropharynx can significantly aid in their diagnosis and treatment. PMID- 22084180 TI - Soft tissue tumors of the head and neck: imaging-based review of the WHO classification. AB - The World Health Organization (WHO) system for defining and classifying soft tissue tumors is usually applied to lesions that occur in the trunk and extremities, but it also provides an excellent framework for characterizing nonepithelial extraskeletal tumors of the head and neck. Although nonepithelial extraskeletal tumors are in the minority among head and neck lesions, they are by no means rare. The WHO classification system recognizes nine major types based on histologic differentiation: adipocytic, fibroblastic or myofibroblastic, fibrohistiocytic, smooth muscle, skeletal muscle, vascular, pericytic, and chondro-osseous tumors, as well as soft tissue tumors of uncertain differentiation. Tumors of each histologic type may be further subclassified on the basis of their biologic behavior as benign, intermediate (ie, having malignant potential), or malignant. Imaging plays an important role in the noninvasive diagnosis and characterization of nonepithelial soft tissue tumors of the head and neck, providing clues about tumor grade, composition, extent, and involvement of adjacent structures. Although the imaging characteristics of many such tumors are nonspecific, consideration of the clinical history in concert with the imaging findings may help limit the differential diagnosis or even allow reliable diagnosis of some of these tumors. PMID- 22084181 TI - Distinguishing breast skin lesions from superficial breast parenchymal lesions: diagnostic criteria, imaging characteristics, and pitfalls. AB - Superficial lesions are commonly encountered in the breast and may be located in the dermis, hypodermis (subcutaneous fat), or parenchyma. The differential diagnosis varies for each anatomic layer. Dermal lesions that are seen by breast imagers are usually benign skin cysts. Hypodermal lesions, although usually benign, may include lesions that arise from anterior terminal duct lobular units and include papilloma, adenosis, fibroadenoma, and breast cancer. To avoid misclassifying a small superficial breast cancer as a benign dermal lesion, it is necessary to understand superficial breast and skin anatomy and the mammographic, ultrasonographic (U.S.), and magnetic resonance (MR) imaging signs that indicate that a lesion is dermal. Mammography is the optimal modality for localizing calcifications to the dermis or hypodermis. However, U.S. typically has higher resolution for localizing masses than mammography and MR imaging. At US, a lesion may be categorized as dermal (a) if it is contained entirely within the dermis, (b) if a tract that extends from the lesion to the skin is seen, or (c) if a claw of tissue surrounding the margin of the lesion is present. As with other breast lesions, suspicious imaging features should be sought in addition to determining the anatomic origin. If histologic analysis is necessary to characterize lesions with an unknown cause or origin, precautions must be taken to decrease patient morbidity. PMID- 22084182 TI - Paget disease of the breast: mammographic, US, and MR imaging findings with pathologic correlation. AB - Paget disease is a rare malignancy of the breast characterized by infiltration of the nipple epidermis by adenocarcinoma cells. The clinical features of Paget disease are characteristic and should increase the likelihood of the diagnosis being made. An important point is that more than 90% of cases of Paget disease are associated with an additional underlying breast malignancy. Paget disease is frequently associated with ductal carcinoma in situ (DCIS) in the underlying lactiferous ducts of the nipple-areolar complex; it may even be associated with DCIS or invasive breast cancer elsewhere in the breast, at least 2 cm from the nipple-areolar complex. Nevertheless, mammographic findings may be negative in up to 50% of cases. Magnetic resonance (MR) imaging can be useful in patients with Paget disease for evaluation of the nipple-areolar complex and identification of an additional underlying malignancy in the breast. The appropriate surgical treatment must be carefully selected and individualized on the basis of radiologic findings, especially those obtained with breast MR imaging. PMID- 22084183 TI - saline-infused sonohysterography: tips for achieving greater success. AB - Saline-infused sonohysterography (SIS) may help improve visualization of the endometrium and endometrial cavity and assess tubal patency. Although most SIS procedures are straightforward, a variety of pitfalls may lead to an unsuccessful procedure or incomplete evaluation. SIS should be scheduled between days 4 and 10 of the patient's menstrual cycle, when the endometrium is at its thinnest, and physiologic changes during the secretory phase are not present. Performing preprocedure imaging serves many purposes, such as depicting hydrosalpinx, causes of uterine and adnexal tenderness, and pelvic inflammatory disease, as well as assessing the size and position of the uterus and the orientation of the cervix. It is important not to presume that fibroids are the cause of bleeding when the endometrium is obscured at preprocedure imaging. Obstacles to a successful procedure include issues related to patient anxiety and discomfort, which may be prevented or minimized at almost every step of the procedure. Inability to obtain access to the cervix is the most common cause of unsuccessful SIS; proper patient positioning in a semi-upright lithotomy position is important. Injection of air during any US-guided procedure may lead to shadowing that obscures the region of interest. Adequate distention of the endometrial cavity is crucial for successful SIS, and optimal positioning of the distended balloon may improve the degree of distention. However, poor distention may be indicative of an underlying pathologic condition. Knowledge of these pitfalls and the strategies to overcome them may prevent premature or unnecessary termination of an otherwise successful study. PMID- 22084184 TI - Pelvic reconstruction with omental and VRAM flaps: anatomy, surgical technique, normal postoperative findings, and complications. AB - Soft-tissue reconstruction of the pelvis with vascularized tissue flaps has become an increasingly common procedure. The types of flaps and the indications for their use vary, but all flap procedures are performed with the goal of transferring tissue from a donor site to a recipient site to restore form and function, obliterate dead space, and create an environment favorable to wound healing. Oncologic surgeries, including total pelvic exenteration and abdominoperineal resection, are the leading indications for pelvic reconstruction. The pedicle flaps most commonly used for pelvic reconstruction following these oncologic interventions are the vertical rectus abdominis myocutaneous flap (VRAM) and the omental pedicle flap. Familiarity with the surgical techniques used for pelvic reconstruction with these flaps is crucial for the accurate interpretation of cross-sectional imaging studies, allowing the radiologist to distinguish between normal postoperative findings and complications or recurrent disease. PMID- 22084185 TI - Imaging manifestations of abdominal fat necrosis and its mimics. AB - Intraabdominal fat is a metabolically active tissue that may undergo necrosis through a number of mechanisms. Fat necrosis is a common finding at abdominal cross-sectional imaging, and it may cause abdominal pain, mimic findings of acute abdomen, or be asymptomatic and accompany other pathophysiologic processes. Common processes that are present in fat necrosis include torsion of an epiploic appendage, infarction of the greater omentum, and fat necrosis related to trauma or pancreatitis. In addition, other pathologic processes that involve fat may be visualized at computed tomography, including focal lipohypertrophy, pathologic fat paucity (lipodystrophies), and malignancies such as liposarcoma, which may mimic benign causes of fat stranding. Because fat necrosis and malignant processes such as liposarcoma and peritoneal carcinomatosis may mimic one another, knowledge of a patient's clinical history and prior imaging studies is essential for accurate diagnosis. PMID- 22084186 TI - AIRP best cases in radiologic-pathologic correlation: spindle cell carcinoma of the esophagus. PMID- 22084188 TI - Interpretation of SPECT/CT myocardial perfusion images: common artifacts and quality control techniques. AB - Nuclear medicine has long played an important role in the noninvasive evaluation of known or suspected coronary artery disease. The development of single photon emission computed tomography (SPECT) led to improved assessments of myocardial perfusion, and the use of electrocardiographic gating made accurate measurements of ventricular wall motion, ejection fractions, and ventricular volumes possible. With the use of hybrid SPECT/computed tomography (CT) scanning systems, the cardiac functional parameters can be measured in a single imaging session. These recent advances in imaging technology have not only enhanced image quality but also improved diagnostic sensitivity and specificity in the detection of clinically relevant coronary artery disease. The CT-based attenuation maps obtained with hybrid SPECT/CT systems also have been useful for improving diagnostic accuracy. However, when attenuation correction and other advanced image data postprocessing techniques are used, unexpected artifacts may arise. The artifacts most commonly encountered are related to the characteristics either of the technology or of the patient. Thus, close attention to the details of acquisition protocols, processing techniques, and image interpretation is needed to ensure high diagnostic quality in myocardial perfusion studies. PMID- 22084189 TI - Novel oncologic drugs: what they do and how they affect images. AB - Targeted therapies are designed to interfere with specific aberrant biologic pathways involved in tumor development. The main classes of novel oncologic drugs include antiangiogenic drugs, antivascular agents, drugs interfering with EGFR HER2 or KIT receptors, inhibitors of the PI3K/Akt/mTOR pathway, and hormonal therapies. Cancer cells usurp normal signal transduction pathways used by growth factors to stimulate proliferation and sustain viability. The interaction of growth factors with their receptors activates different intracellular pathways affecting key tumor biologic processes such as neoangiogenesis, tumor metabolism, and tumor proliferation. The response of tumors to anticancer therapy can be evaluated with anatomic response assessment, qualitative response assessment, and response assessment with functional and molecular imaging. Angiogenesis can be measured by means of perfusion imaging with computed tomography and magnetic resonance (MR) imaging. Diffusion-weighted MR imaging allows imaging evaluation of tumor cellularity. The main imaging techniques for studying tumor metabolism in vivo are positron emission tomography and MR spectroscopy. Familiarity with imaging findings secondary to tumor response to targeted therapies may help the radiologist better assist the clinician in accurate evaluation of tumor response to these anticancer treatments. Functional and molecular imaging techniques may provide valuable data and augment conventional assessment of tumor response to targeted therapies. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.317115108/-/DC1. PMID- 22084190 TI - Radiologic assessment of response to therapy: comparison of RECIST Versions 1.1 and 1.0. AB - Improvements in radiologic imaging technology and therapeutic options available for management of tumors have necessitated the revision of guidelines for the imaging-based assessment of tumor response to therapy. The purpose of this article is to familiarize radiologists with the modifications to the Response Evaluation Criteria in Solid Tumors (RECIST) that have been incorporated in the latest version of the guidelines, RECIST 1.1. The most important differences between this version and the previous one, RECIST 1.0, include reductions in the maximum number of lesions per patient and per organ that may be targeted for measurement, augmentation of the criteria defining progressive disease, additional guidelines for reporting findings of lesions that are too small to measure and for measuring lesions that appear to have fragmented or coalesced at follow-up imaging, new criteria for characterizing lymphadenopathy, new criteria for selecting bone lesions and cystic lesions as targets for measurement, and the inclusion of findings at positron emission tomography among the indicators of disease response. PMID- 22084191 TI - Vascular abnormalities of the breast: arterial and venous disorders, vascular masses, and mimic lesions with radiologic-pathologic correlation. AB - Vascular abnormalities of the breast include a wide spectrum of arterial and venous disorders, as well as benign and malignant vascular masses. Multimodality imaging is often necessary to accurately diagnose several of these uncommon conditions, and pathologic correlation can be important for accurate diagnosis of vascular masses. After a review of the vascular anatomy of the breast, the authors discuss the imaging appearance of several native arterial disorders (atherosclerosis and aneurysm) and venous disorders (superior vena cava syndrome, congestive heart failure, thrombophlebitis, and varix). Benign vascular tumors (hemangioma, lymphangioma, and angiolipoma) and malignant vascular tumors (angiosarcoma and hemangiopericytoma) that may be encountered in the breast are also reviewed. In addition, pitfalls in the correct interpretation of vascular breast lesions (devascularization of masses and pathologic mimics) are reviewed. Understanding and assessing normal and pathologic breast vasculature will permit more accurate diagnosis and treatment planning and allow breast imagers to have a more active role in breast care. PMID- 22084192 TI - Enlargement of the inferior intercavernous sinus: a new sign for the diagnosis of craniospinal hypotension. PMID- 22084193 TI - Dabigatran. PMID- 22084194 TI - Bone marrow therapy for myocardial infarction. PMID- 22084196 TI - BGMUT: NCBI dbRBC database of allelic variations of genes encoding antigens of blood group systems. AB - Analogous to human leukocyte antigens, blood group antigens are surface markers on the erythrocyte cell membrane whose structures differ among individuals and which can be serologically identified. The Blood Group Antigen Gene Mutation Database (BGMUT) is an online repository of allelic variations in genes that determine the antigens of various human blood group systems. The database is manually curated with allelic information collated from scientific literature and from direct submissions from research laboratories. Currently, the database documents sequence variations of a total of 1251 alleles of all 40 gene loci that together are known to affect antigens of 30 human blood group systems. When available, information on the geographic or ethnic prevalence of an allele is also provided. The BGMUT website also has general information on the human blood group systems and the genes responsible for them. BGMUT is a part of the dbRBC resource of the National Center for Biotechnology Information, USA, and is available online at http://www.ncbi.nlm.nih.gov/projects/gv/rbc/xslcgi.fcgi?cmd=bgmut. The database should be of use to members of the transfusion medicine community, those interested in studies of genetic variation and related topics such as human migrations, and students as well as members of the general public. PMID- 22084195 TI - Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial. AB - CONTEXT: Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation. OBJECTIVE: To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] <=45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011. INTERVENTIONS: Intracoronary infusion of 150 * 10(6) autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing. MAIN OUTCOME MEASURES: Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size. RESULTS: A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline. CONCLUSION: Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00684060. PMID- 22084197 TI - AP endonuclease independent repair of abasic sites in Schizosaccharomyces pombe. AB - Abasic (AP) sites are formed spontaneously and are inevitably intermediates during base excision repair of DNA base damages. AP sites are both mutagenic and cytotoxic and key enzymes for their removal are AP endonucleases. However, AP endonuclease independent repair initiated by DNA glycosylases performing beta,delta-elimination cleavage of the AP sites has been described in mammalian cells. Here, we describe another AP endonuclease independent repair pathway for removal of AP sites in Schizosaccharomyces pombe that is initiated by a bifunctional DNA glycosylase, Nth1 and followed by cleavage of the baseless sugar residue by tyrosyl phosphodiesterase Tdp1. We propose that repair is completed by the action of a polynucleotide kinase, a DNA polymerase and finally a DNA ligase to seal the gap. A fission yeast double mutant of the major AP endonuclease Apn2 and Tdp1 shows synergistic increase in MMS sensitivity, substantiating that Apn2 and Tdp1 process the same substrate. These results add new knowledge to the complex cellular response to AP sites, which could be exploited in chemotherapy where synthetic lethality is a key strategy of treatment. PMID- 22084198 TI - PLEXdb: gene expression resources for plants and plant pathogens. AB - PLEXdb (http://www.plexdb.org), in partnership with community databases, supports comparisons of gene expression across multiple plant and pathogen species, promoting individuals and/or consortia to upload genome-scale data sets to contrast them to previously archived data. These analyses facilitate the interpretation of structure, function and regulation of genes in economically important plants. A list of Gene Atlas experiments highlights data sets that give responses across different developmental stages, conditions and tissues. Tools at PLEXdb allow users to perform complex analyses quickly and easily. The Model Genome Interrogator (MGI) tool supports mapping gene lists onto corresponding genes from model plant organisms, including rice and Arabidopsis. MGI predicts homologies, displays gene structures and supporting information for annotated genes and full-length cDNAs. The gene list-processing wizard guides users through PLEXdb functions for creating, analyzing, annotating and managing gene lists. Users can upload their own lists or create them from the output of PLEXdb tools, and then apply diverse higher level analyses, such as ANOVA and clustering. PLEXdb also provides methods for users to track how gene expression changes across many different experiments using the Gene OscilloScope. This tool can identify interesting expression patterns, such as up-regulation under diverse conditions or checking any gene's suitability as a steady-state control. PMID- 22084199 TI - Solution structure and DNA-binding properties of the phosphoesterase domain of DNA ligase D. AB - The phosphoesterase (PE) domain of the bacterial DNA repair enzyme LigD possesses distinctive manganese-dependent 3'-phosphomonoesterase and 3'-phosphodiesterase activities. PE exemplifies a new family of DNA end-healing enzymes found in all phylogenetic domains. Here, we determined the structure of the PE domain of Pseudomonas aeruginosa LigD (PaePE) using solution NMR methodology. PaePE has a disordered N-terminus and a well-folded core that differs in instructive ways from the crystal structure of a PaePE*Mn(2+)* sulfate complex, especially at the active site that is found to be conformationally dynamic. Chemical shift perturbations in the presence of primer-template duplexes with 3' deoxynucleotide, 3'-deoxynucleotide 3'-phosphate, or 3' ribonucleotide termini reveal the surface used by PaePE to bind substrate DNA and suggest a more efficient engagement in the presence of a 3'-ribonucleotide. Spectral perturbations measured in the presence of weakly catalytic (Cd(2+)) and inhibitory (Zn(2+)) metals provide evidence for significant conformational changes at and near the active site, compared to the relatively modest changes elicited by Mn(2+). PMID- 22084200 TI - AH-DB: collecting protein structure pairs before and after binding. AB - This work presents the Apo-Holo DataBase (AH-DB, http://ahdb.ee.ncku.edu.tw/ and http://ahdb.csbb.ntu.edu.tw/), which provides corresponding pairs of protein structures before and after binding. Conformational transitions are commonly observed in various protein interactions that are involved in important biological functions. For example, copper-zinc superoxide dismutase (SOD1), which destroys free superoxide radicals in the body, undergoes a large conformational transition from an 'open' state (apo structure) to a 'closed' state (holo structure). Many studies have utilized collections of apo-holo structure pairs to investigate the conformational transitions and critical residues. However, the collection process is usually complicated, varies from study to study and produces a small-scale data set. AH-DB is designed to provide an easy and unified way to prepare such data, which is generated by identifying/mapping molecules in different Protein Data Bank (PDB) entries. Conformational transitions are identified based on a refined alignment scheme to overcome the challenge that many structures in the PDB database are only protein fragments and not complete proteins. There are 746,314 apo-holo pairs in AH-DB, which is about 30 times those in the second largest collection of similar data. AH-DB provides sophisticated interfaces for searching apo-holo structure pairs and exploring conformational transitions from apo structures to the corresponding holo structures. PMID- 22084201 TI - Improving patient safety via automated laboratory-based adverse event grading. AB - The identification and grading of adverse events (AEs) during the conduct of clinical trials is a labor-intensive and error-prone process. This paper describes and evaluates a software tool developed by City of Hope to automate complex algorithms to assess laboratory results and identify and grade AEs. We compared AEs identified by the automated system with those previously assessed manually, to evaluate missed/misgraded AEs. We also conducted a prospective paired time assessment of automated versus manual AE assessment. We found a substantial improvement in accuracy/completeness with the automated grading tool, which identified an additional 17% of severe grade 3-4 AEs that had been missed/misgraded manually. The automated system also provided an average time saving of 5.5 min per treatment course. With 400 ongoing treatment trials at City of Hope and an average of 1800 laboratory results requiring assessment per study, the implications of these findings for patient safety are enormous. PMID- 22084202 TI - Prevalence rate and dentoskeletal features associated with buccally displaced maxillary canines. AB - The aim of the study was to analyse the prevalence and distribution of buccally displaced canines (BDCs) in subjects scheduled for orthodontic treatment and to investigate the association between BDC and sagittal, vertical, and transverse dentoskeletal relationships. A study sample of 1852 subjects was examined, and it was divided randomly into two groups. A first group of 252 subjects served as control group: the 'reference' prevalence rates for the examined parameters were calculated in this group. The remaining 1600 subjects comprised the sample from which the experimental BDC group was derived. Presence of unilateral or bilateral maxillary BDC, ANB, and SN GOGn angles for sagittal and vertical skeletal relationships, intercanine and intermolar distances, and tooth crowding at the maxillary arch were recorded for each subject. The statistical significance of differences between the BDC and the control groups in transverse relations and tooth crowding at the upper arch was tested by means of independent sample t tests. Chi-square tests were performed to compare the prevalence rates of BDC and also sagittal and vertical skeletal features in the two groups. The prevalence rate of BDC was 3.06 per cent with a male-to-female ratio of 1:1. BDC subjects exhibited a significant association with hyperdivergent skeletal relationships (38.8%), reduced maxillary intercanine width, and crowding in the upper arch. The presence of specific dentoskeletal characteristics can be considered as a risk indicator for developing a buccal displacement of upper permanent canines. PMID- 22084203 TI - Prognostic implications of dipyridamole cardiac MR imaging: a prospective multicenter registry. AB - PURPOSE: To evaluate dipyridamole cardiac magnetic resonance (MR) imaging in the prediction of major events (MEs) in patients with ischemic chest pain in a large multicenter registry. MATERIALS AND METHODS: Institutional ethics committee approval and written informed consent were obtained. A total of 1722 patients who were undergoing cardiac MR imaging for chest pain were included. Wall motion abnormalities (WMAs) at rest, hyperemia perfusion defect (PD), late gadolinium enhancement (LGE), and inducible WMA were analyzed (abnormal if more than one abnormal segment was seen) with the 17-segment model. A cardiac MR categorization was created: category 1, no PD, LGE, or inducible WMA; category 2, PD without LGE and inducible WMA; category 3, LGE without inducible WMA; and category 4, inducible WMA. The association with ME was analyzed by using Cox proportional hazard regression multivariate models. RESULTS: During a median follow-up period of 308 days, 61 MEs (4%) occurred (36 cardiac deaths, 25 nonfatal myocardial infarctions). MEs were associated with a greater extent of WMA, PD, LGE, and inducible WMA (P <= .001 for all analyses). In multivariable analyses, PD (P = .002) and inducible WMA (P = .0001) were the only cardiac MR predictors. ME rate in categories 1, 2, 3, and 4 was 2% (14 of 901 patients), 3% (six of 219 patients), 4% (15 of 409 patients), and 14% (26 of 193 patients), respectively (category 4 vs category 1, adjusted P < .001). Cardiac MR-directed revascularization was performed in 242 patients (14%) and reduced the risk of ME in only category 4 (7% [six of 92 patients] vs 26% [26 of 101 patients], P = .0004). CONCLUSION: Dipyridamole cardiac MR imaging can be used to predict MEs in patients with ischemic chest pain. Patients with inducible WMA are at the highest risk for MEs and benefit the most from revascularization. PMID- 22084204 TI - Vasculitis: molecular imaging by targeting the inflammatory enzyme myeloperoxidase. AB - PURPOSE: To determine if a molecular imaging approach targeting the highly oxidative enzyme myeloperoxidase (MPO) can help noninvasively identify and confirm sites of vascular wall inflammation in a murine model of vasculitis. MATERIALS AND METHODS: Animal experiments were approved by the institutional animal care committee. Twenty-six mice were studied, including eight MPO deficient and six sham-operated mice as controls. Vasculitis was induced with intraperitoneal injection of Candida albicans water-soluble fraction (CAWS). Aortic root magnetic resonance imaging was performed after intravenous injection of the activatable MPO sensor (bis-5-hydroxytryptamide diethylenetriaminepentatacetate gadolinium) (n = 23), referred to as MPO-Gd, or gadopentetate dimeglumine (n = 10). Seven mice were randomly assigned to receive either MPO-Gd or gadopentetate dimeglumine first. Aortic root specimens were collected for biochemical and histopathologic analyses to validate imaging findings. Statistical significance was calculated for contrast-to-noise ratios (CNRs) by using the paired t test. RESULTS: In the aortic root, the mean MPO-Gd CNRs after agent injection (CNR = 28.1) were more than 2.5-fold higher than those of sham-operated mice imaged with MPO-Gd and vasculitis mice imaged with gadopentetate dimeglumine (CNR = 10.6) (P < .05). MPO-Gd MR imaging helped identify areas of vasculitis that were not seen at unenhanced and contrast material-enhanced imaging with gadopentetate dimeglumine. Histopathologic and biochemical analyses for MPO and myeloid cells confirmed imaging findings. In MPO deficient mice, injection of CAWS did not result in a vasculitis phenotype, implying a key role of the imaging target in disease cause. CONCLUSION: Molecular imaging targeting MPO can be a useful biomarker to noninvasively detect and confirm inflammation in vasculitis by using a murine model of Kawasaki disease. PMID- 22084205 TI - Chronic multiple sclerosis lesions: characterization with high-field-strength MR imaging. AB - PURPOSE: To elucidate the mechanism of magnetic resonance (MR) imaging contrast in multiple sclerosis (MS) lesion appearance by using susceptibility-weighted imaging and to assess with histologic correlation the role of iron and myelin in generating this MR imaging contrast. MATERIALS AND METHODS: Each patient provided written consent to a human subject protocol approved by an institutional review board. High-spatial-resolution susceptibility-weighted 7.0-T MR images were obtained in 21 patients with MS. Contrast patterns in quantitative phase and R2* images, derived from 7.0-T data, were investigated in 220 areas defined as chronic MS lesions on conventional T2-weighted fluid-attenuated inversion recovery, T2-weighted, and T1-weighted spin-echo images. The presence of positive or negative phase shifts (ie, decreased or increased MR frequency, respectively) was assessed in each lesion. In addition, postmortem MR imaging was performed at 7.0 T and 11.7 T, and its results were correlated with those of immunohistochemical staining specific for myelin, iron, and ferritin. RESULTS: The majority (133 [60.5%] of 220) of the identified lesions had a normal phase and reduced R2*. A substantial fraction of the lesions (84 [38.2%] of 220) had negative phase shift, either uniformly or at their rim, and a variety of appearances on R2* maps. These two lesion contrast patterns were reproduced in the postmortem MR imaging study. Comparison with histologic findings showed that, while R2* reduction corresponded to severe loss of both iron and myelin, negative phase shift corresponded to focal iron deposits with myelin loss. CONCLUSION: Combined analysis of 7.0-T R2* and phase data may help in characterizing the pathologic features of MS lesions. The observed R2* decreases suggest profound myelin loss, whereas negative phase shifts suggest a focal iron accumulation. PMID- 22084206 TI - Reduced iodine load at CT pulmonary angiography with dual-energy monochromatic imaging: comparison with standard CT pulmonary angiography--a prospective randomized trial. AB - PURPOSE: To compare quantitative and subjective image quality and radiation dose between standard computed tomographic (CT) pulmonary angiography (CTPA) and CTPA with a dual-energy technique with reduced iodine load. MATERIALS AND METHODS: This prospective study was approved by the institutional review board and each participant provided informed consent. Ninety-four patients (59% male; mean age +/- standard deviation, 62 years +/- 15) were randomized to one of two protocols: standard CTPA (100-120 kVp) with standard contrast medium injection (n = 46) and dual-energy CTPA (image reconstruction at 50 keV) with the same injection volume as in the standard protocol but composed of contrast medium and saline in a 1:1 fashion, resulting in 50% reduction in iodine load (n = 48). Signal intensity and noise in three central and two segmental pulmonary arteries were measured; signal to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. A five point scale was used to subjectively evaluate vascular enhancement and image noise. The proportion of diagnostic (score, >= 3) studies and the interreader agreement regarding the dichotomized diagnostic versus nondiagnostic scale were compared between the two groups. RESULTS: Compared with standard CTPA, dual energy CTPA demonstrated higher signal intensity in all pulmonary arteries (all P < .01), inferior noise only in segmental arteries (P < .05), higher SNR and CNR (both P < .05), and compatible effective dose (P > .05). The five-point score was higher in the standard CTPA protocol (P < .05). The interreader agreement regarding the dichotomized diagnostic versus nondiagnostic scale was similar (P > .05) between the two groups. CONCLUSION: Dual-energy CTPA with image reconstruction at 50 keV allows a significant reduction in iodine load while improving intravascular signal intensity, maintaining SNR and with comparable radiation dose. PMID- 22084207 TI - Determination of grade and subtype of meningiomas by using histogram analysis of diffusion-tensor imaging metrics. AB - PURPOSE: To determine whether histogram analysis of diffusion-tensor (DT) magnetic resonance (MR) imaging metrics, including tensor shape measurements, can help determine the grades and subtypes of meningiomas. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study. Nine atypical, three anaplastic, and 39 typical meningiomas were retrospectively studied. The 39 typical meningiomas included one secretory meningioma and 11 fibroblastic, 11 transitional, 14 meningothelial, and two angiomatous meningiomas. DT imaging metrics, including fractional anisotropy, mean diffusivity, linear anisotropy coefficient, planar anisotropy coefficient (CP), spherical anisotropy coefficient (CS), and eigenvalue skewness (SK), as well as normalized signal intensity from contrast-enhanced T1- and T2-weighted images, were measured from the enhancing region of the tumor. Mean, variance, skewness, and kurtosis were extracted from the histograms. A two-level decision tree was designed, and a multivariate logistic regression analysis was used at each level to determine the best model for classification. RESULTS: Histogram skewness of SK and kurtosis of SK were significantly higher in atypical and anaplastic meningiomas than in typical meningiomas (P<.01). Among typical meningiomas, significant differences in histogram measures of CP and CS between fibroblastic meningiomas and other subtypes were observed (P<.01). The best model for differentiating atypical and anaplastic meningiomas from typical meningiomas consisted of mean and skewness of SK and kurtosis of T1 signal intensity, with an area under the receiver operating characteristic curve (AUC) of 0.946. The best model for differentiating fibroblastic meningiomas from other subtypes consisted of skewness of T2 signal intensity and kurtosis of CP (AUC, 0.970). CONCLUSION: Histogram analysis of DT imaging metrics can help determine the grades and subtypes of meningiomas, which can better assist in surgical planning. PMID- 22084208 TI - New reference values for the neonatal cerebral ventricles. AB - PURPOSE: To establish new cross-sectional reference values for the size of the lateral ventricles in a large cohort of neonates between 24 and 42 weeks' gestational age (GA) as well as longitudinal reference values for the follow-up of very preterm infants born at less than 30 weeks' gestation. MATERIALS AND METHODS: Institutional review board approval and parental written informed consent were obtained for this prospective cohort study of 625 neonates (58% male patients) with a median GA of 33.4 weeks (range, 24.7-42.6 weeks). All infants underwent cranial ultrasonography (US) within 4 days after birth to evaluate the size of the lateral ventricles. Scanning was repeated in 301 preterm and term neonates within the 1st week of life to assess the presence of ventricular reopening. Seventy-nine very preterm infants (GA, <30 weeks) were prospectively included for cranial US at term-equivalent age (TEA). US measurements were performed of the ventricular index (VI), anterior horn width (AHW), and thalamo occipital distance (TOD). Statistical analysis was conducted by using a paired t test, multilevel analysis, and analysis of covariance. RESULTS: Cross-sectional reference values for the VI and TOD increased with maturity, whereas the AHW remained constant. Vaginal birth was independently associated with a slightly smaller AHW following birth and with an increase in AHW within the 1st week of life (P < .05). Preterm-born infants showed a larger ventricular size at TEA compared with term infants (P < .001). CONCLUSION: New cross-sectional and longitudinal reference curves were established for the size of the neonatal lateral ventricles, which may allow for early identification and quantification of ventriculomegaly due to either posthemorrhagic ventricular dilation or periventricular white matter loss. PMID- 22084209 TI - Distinguishing benign from malignant masses at breast US: combined US elastography and color doppler US--influence on radiologist accuracy. AB - PURPOSE: To investigate the effect of the combined use of ultrasonographic (US) elastography and color Doppler US on the accuracy of radiologists in distinguishing benign from malignant nonpalpable breast masses and in making the decision for biopsy recommendations at B-mode US. MATERIALS AND METHODS: This prospective study was conducted with institutional review board approval; written informed consent was obtained. A cohort of 367 biopsy-proved cases in 319 women (age range, 22-78 years; mean age, 48.6 years) with B-mode US, US elastographic, and Doppler US images was included. Five blinded readers independently scored the likelihood of malignancy for four data sets (ie, B-mode US alone, B-mode US and elastography, B-mode US and Doppler US, and B-mode US, US elastography, and Doppler US). The area under the receiver operating characteristic curve (A(z)) values, sensitivities, and specificities of each data set were compared. RESULTS: The A(z) of B-mode US, US elastography, and Doppler US (average, 0.844; range, 0.797-0.876) was greater than that of B-mode US alone (average, 0.771; range, 0.738-0.798) for all readers (P = .001 for readers 1, 2, and 3; P < .001 for reader 4; P = .002 for reader 5). When both elastography and Doppler scores were negative, leading to strict downgrading, the specificity increased for all readers from an average of 25.3% (75.4 of 298; range, 6.4%-40.9%) to 34.0% (101.2 of 298; range, 26.5%-48.7%) (P < .001 for readers 1, 2, 4, and 5; P = .016 for reader 3) without a significant change in sensitivity. CONCLUSION: Combined use of US elastography and color Doppler US increases both the accuracy in distinguishing benign from malignant masses and the specificity in decision making for biopsy recommendation at B-mode US. PMID- 22084210 TI - When does a radiologist's recommendation for follow-up result in high-cost imaging? AB - PURPOSE: To measure the proportion of high-cost imaging generated by a radiologist's recommendation and to identify the imaging findings resulting in follow-up. MATERIALS AND METHODS: This retrospective HIPAA-compliant study had institutional review board approval, with waiver of informed consent. A recommended examination was defined as one performed within a single episode of care (defined as fewer than 60 days after the initial imaging) following a radiologist's recommendation in a prior examination report. Chest and abdominal computed tomography (CT), brain and lumbar spine magnetic resonance (MR) imaging, and body positron emission tomography were included for analysis. From a database of all radiology examinations (approximately 200,000) at one institution over a 6 month period, a computerized search identified all high-cost examinations that were preceded by an examination containing a radiologist recommendation. Medical records were reviewed to verify accuracy of the recommending-recommended examination pairs and to determine the reason for the radiologist's recommendation. For proportions, 95% confidence intervals were calculated. RESULTS: Overall, 1558 of 29,232 (5.3%) high-cost examinations followed a radiologist's recommendation. Chest CT was the high-cost examination most often resulting from a radiologist's recommendation (878 of 9331, 9.4%), followed by abdominal CT (390 of 10,258, 3.8%) and brain MR imaging (222 of 6436, 3.4%). The examination types with the highest numbers of follow-up examinations were chest radiography (n=431), chest CT (n=410), abdominal CT (n=214), and abdominal ultrasonography (n=120). The most common findings resulting in follow-up were pulmonary nodules or masses (559 of 1558, 35.9%), other pulmonary abnormalities (150 of 1558, 9.6%), adenopathy (103 of 1558, 6.6%), renal lesions (101 of 1558, 6.5%), and negative examination findings (101 of 1558, 6.5%). CONCLUSION: Radiologists' recommendations account for only a small proportion of outpatient high-cost imaging examinations. Pulmonary nodule follow-up is the most common cause for radiologist-generated examinations. PMID- 22084211 TI - Acute lower intestinal bleeding: feasibility and diagnostic performance of CT angiography. AB - PURPOSE: To assess the diagnostic performance of computed tomographic (CT) angiography as the initial diagnostic examination for patients presenting to the emergency room with acute lower intestinal bleeding. MATERIALS AND METHODS: The study was reviewed and approved by the ethics committee, and written informed consent was obtained from each patient or their closest relative when the clinical condition precluded consent by the patient. This prospective study comprised 47 patients (27 men, 20 women; mean age, 68 years) with acute lower gastrointestinal tract bleeding who were referred to undergo emergency colonoscopy for evaluation. CT angiography was performed in all patients shortly after arrival to the emergency room. Findings identified at CT angiography included active extravasation (ongoing hemorrhage) or hyperattenuating intraluminal contents on noncontrast material-enhanced images (recent hemorrhage). Presence and location of bleeding and likely cause of hemorrhage were determined and compared with the standard of reference (angiography, colonoscopy, or surgical findings). Data collected were analyzed with a statistical software package. Sensitivity, specificity, and positive and negative predictive values of CT angiography in depicting ongoing or recent hemorrhage were calculated and compared with those of standard of reference. RESULTS: CT angiography demonstrated active bleeding in 14 patients and intraluminal hyperattenuating material in six patients. The sensitivity, specificity, positive predictive value, and negative predictive value of CT angiography in depicting active or recent bleeding were 100% (19 of 19), 96% (27 of 28), 95% (19 of 20), and 100% (27 of 27), respectively. Findings of CT angiography and the standard of reference were concordant for determining definite or potential cause of bleeding in 44 of 47 patients (93% accuracy). CONCLUSION: CT angiography performed in the emergency setting in patients with acute lower intestinal bleeding is feasible and correctly depicts the presence and location of active or recent hemorrhage, as well as the potential cause, in the majority of patients. PMID- 22084212 TI - Roadway characteristics and pediatric pedestrian injury. AB - Changing the built environment is a sound, but often underutilized approach to injury control. The authors reviewed the literature and conducted a meta-analysis to synthesize the evidence on the association of roadway characteristics with risk of pediatric pedestrian injury. To synthesize the data, they converted results to odds ratios based on direct results or abstracted outcomes and used Bayesian meta-analytic approaches by modeling outcomes as the logit of a normally distributed set of outcomes with vague prior distributions for the central measure of effect and its variance. On the basis of 10 studies of roadway features restricted exclusively to pediatric populations, the synthesized effect estimate for the association of roadway characteristics with pedestrian injury risk was 2.5 (95% credible interval: 1.8, 3.2). The probability of a new study showing an association between the built roadway and pediatric pedestrian injury was nearly 100%. The authors concluded that the built environment is directly related to the risk of pedestrian injury. This review and meta-analysis suggests that even modest interventions to the built roadway environment may result in meaningful reductions in the risk of pediatric pedestrian injury. PMID- 22084213 TI - Postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin for the treatment of high-risk retinoblastoma. AB - BACKGROUND: Analysis of 52 eyes with high-risk retinoblastoma managed with postenucleation adjuvant chemotherapy using vincristine sulfate, etoposide phosphate, and carboplatin showed no evidence of systemic metastasis in any case during a mean (range) follow-up of 66 (12-202) months. PURPOSE: To determine the efficacy of postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin in the prevention of metastasis for patients with high-risk retinoblastoma. METHODS: Retrospective, nonrandomized, interventional case series of 52 eyes in 51 patients with high-risk retinoblastoma consisting of tumor invasion into the anterior segment, posterior uvea 3 mm or greater, postlaminar optic nerve, or any combination of posterior uvea and optic nerve involvement. RESULTS: Of 51 consecutive patients with high-risk retinoblastoma, there were 30 males (59%) and 21 females (41%), with a median age of 28 months at diagnosis. All 52 eyes were classified as group E. The main histopathologic risk factors included anterior segment invasion (7 [13%]), isolated massive posterior uveal invasion of 3 mm or greater (6 [12%]), isolated postlaminar optic nerve invasion (15 [29%]), or any posterior uveal invasion with any optic nerve involvement (24 [46%]). There was additional invasion into the sclera (3 [6%]) and extrascleral structures, including the orbit (1 [2%]). A single histopathologic high-risk factor was present in 32 eyes (62%), whereas 20 eyes (38%) manifested 2 or more high-risk characteristics. Based on previously published series, untreated high risk retinoblastoma carries at least a 24% risk for metastatic disease. In the present series, using vincristine, etoposide, and carboplatin in all cases, there was no metastasis during a mean follow-up of 66 months (median [range], 55 [12 202] months). CONCLUSIONS: Retinoblastoma with invasion into the postlaminar optic nerve and/or posterior uvea is at high risk for metastasis and death. In this study, postenucleation chemotherapy using vincristine, etoposide, and carboplatin was effective in preventing metastasis in every case (100%). PMID- 22084214 TI - Outcomes of integrating genetics in management of patients with retinoblastoma. AB - OBJECTIVE: To present the outcome of a comprehensive team approach to provide genetic evaluation and testing for a large cohort of children diagnosed with retinoblastoma. METHODS: The multidisciplinary team included pediatric oncologists, an ophthalmologist, an ophthalmic pathologist, a geneticist, and genetic counselors. Retrospective data from 8 years included 90 initial evaluations, of which 81 probands were diagnosed with retinoblastoma (34 bilateral and 47 unilateral) and 9 were evaluated because of a positive family history. RESULTS: Genetic testing was accomplished equivalently in bilateral and unilateral cases in 51 of 81 patients (63%). In 5 of 30 patients (17%), with unilateral disease an RB1 mutation was identified in peripheral blood samples. In another 7 of 30 patients (23%), mutation analysis confirmed the occurrence of sporadic retinoblastoma. Overall, genetic testing of 48 at-risk family members from 21 families revealed 6 individuals positive and 42 negative for the familial mutation. CONCLUSIONS: Our study emphasizes that genetics can be incorporated into the management plan of all retinoblastoma patients using a team approach to ensure timely evaluations and appropriate counseling. Genetic evaluations improved risk prediction for patients and family members as well as prevented overutilization of clinical screening tests, which had potential morbidity for relatives documented to not carry an RB1 mutation. PMID- 22084215 TI - Real-time ophthalmoscopic findings of superselective intraophthalmic artery chemotherapy in a nonhuman primate model. AB - OBJECTIVE: To report real-time ophthalmoscopic findings during superselective intraophthalmic artery chemotherapy (SSIOAC) in a nonhuman primate model. METHODS: Six adult male Rhesus macaques (Macacca mulatta) were randomly assigned to 1 of 2 treatment cohorts: melphalan (5 mg/30 mL) or carboplatin (30 mg/30 mL). Each animal underwent 3 separate SSIOAC procedures at 3-week intervals. Digital retinal images were obtained during each infusion. Intravenous fluorescein angiography was performed immediately after each procedure. RESULTS: All SSIOAC procedures were successfully completed. Toxicities were equally distributed between drug cohorts. Systemic toxicities included mild bone marrow suppression in all animals and anorexia in 1. One animal had greater than 50% narrowing of the treated ophthalmic artery after its second infusion. All 18 procedures (100%) resulted in pulsatile optic nerve and choroid blanching, retinal artery narrowing, and retinal edema. Of the 18 procedures, retinal artery sheathing was found during 17 (94%), and retinal artery precipitates were seen in 10 (56%); choroidal hypoperfusion was seen by fluorescein angiogram in 18 (100%). CONCLUSION: Real-time ophthalmic investigations are useful and, in our nonhuman primate model, indicate prevalent, acute ocular vascular toxicities during SSIOAC. CLINICAL RELEVANCE: Real-time retinal imaging is feasible in a nonhuman primate model of SSIOAC. Application to SSIOAC in children may shed insight into reported vascular toxicities. PMID- 22084216 TI - Aceruloplasminemia: retinal histopathologic manifestations and iron-mediated melanosome degradation. AB - OBJECTIVE: To examine the retinal histopathologic manifestation of aceruloplasminemia, an autosomal recessive disease caused by mutation of the ferroxidase ceruloplasmin, resulting in tissue iron overload. METHODS: The morphologic features of the human aceruloplasminemic retina were studied with light and electron microscopy. Retinal iron accumulation was assessed with Perls Prussian blue staining, immunohistochemistry, and secondary ion mass spectrometry. RESULTS: Light and electron microscopic analysis revealed several ocular pathologic findings that resembled age-related macular degeneration, including retinal pigment epithelium (RPE) depigmentation, atrophy and hypertrophy, nodular and diffuse drusen, and lipofuscin and melanolipofuscin granules. Complement deposition was detected in drusen. The RPE cells and neural retina had increased levels of iron. Two major types of RPE cells were observed: melanosome rich and melanosome poor. Melanosome-rich cells had increased levels of iron and melanolipofuscin. The melanolipofuscin granules were observed in large aggregates, where some of the melanosomes were degrading. Melanosome-poor cells lacked melanosomes, melanolipofuscin, and lipofuscin but contained electron dense aggregates high in iron, phosphorus, and sulfur. CONCLUSIONS: The findings in the aceruloplasminemic retina resemble some of those found in age-related macular degeneration. Also, they suggest that melanosomes in the RPE can be degraded via iron-mediated reactive oxygen species production. CLINICAL RELEVANCE: Mechanisms underlying the pathologic mechanisms found in aceruloplasminemia also may be important in age-related macular degeneration. PMID- 22084217 TI - Phenotypic characterization of 3 families with autosomal dominant retinitis pigmentosa due to mutations in KLHL7. AB - OBJECTIVE: To characterize the visual phenotype caused by mutations in the BTB Kelch protein, KLHL7, responsible for the RP42 form of autosomal dominant retinitis pigmentosa (RP). METHODS: Comprehensive ophthalmic testing included visual acuity, static visual field, kinetic visual field, dark adaptometry, full field electroretinography, spectral-domain optical coherence tomography, and fundus photography. Longitudinal visual function data (range, 15-27 years) were available for some of the affected individuals. RESULTS: We report a phenotypic assessment of 3 unrelated families, each harboring different KLHL7 mutations (c.458C>T, c.449G>A, and c.457G>A). The fundi showed classic signs of RP. Best corrected visual acuity was 20/50 or better in at least one eye up to age 65 years. Static and kinetic visual fields showed concentric constriction to central 10 degrees to 20 degrees by age 65 years; 2 patients with Goldmann perimetry exhibited bilateral visual field retention in the far periphery. Both rod and cone full-field electroretinographic amplitudes were substantially lower than normal, with a decline rate of 3% per year in cone 31-Hz flicker response. Rod and cone activation and inactivation variables were abnormal. Spectral-domain optical coherence tomography indicated retention of foveal inner segment-outer segment junction through age 65 years. CONCLUSIONS: Mutations in KLHL7 are associated with a late-onset form of autosomal dominant retinal degeneration that preferentially affects the rod photoreceptors. Full-field electroretinographic findings, including recovery kinetics, are consistent with those observed in other forms of autosomal dominant RP. CLINICAL RELEVANCE: The phenotypes are similar among patients with 3 types of KLHL7 mutations (c.458C>T, c.449G>A, and c.457G>A). Strong retention of foveal function and bilateral concentric constriction of visual fields with far periphery sparing may guide mutation screening in autosomal dominant RP. PMID- 22084218 TI - Analysis of pars plana vitrectomy for optic pit-related maculopathy with intraoperative optical coherence tomography: a possible connection with the vitreous cavity. AB - Optimal management of optic pit-related maculopathy remains to be determined. The fluid source for the maculopathy also remains controversial. In this article, we present a unique surgical technique for internal drainage of the intraretinal fluid and describe the intraoperative use of spectral-domain optical coherence tomography to assist in the surgical management of this condition. Pars plana vitrectomy was performed with elevation of the posterior hyaloid. Following an air-fluid exchange, aspiration over the optic nerve pit was performed. Following aspiration, intraoperative spectral-domain optical coherence tomography demonstrated collapse of the retinoschisis, strongly suggesting a connection between the vitreous cavity and the intraretinal fluid. PMID- 22084219 TI - Intra-arterial chemotherapy for advanced retinoblastoma: is the time right for a prospective clinical trial? PMID- 22084220 TI - Superselective intraophthalmic artery chemotherapy: what we do not know. PMID- 22084221 TI - Chemosurgery for retinoblastoma: what we know after 5 years. PMID- 22084222 TI - Acute retinal necrosis after herpes zoster vaccination. PMID- 22084223 TI - Vitelliform retinopathy in metastatic cutaneous melanoma with choroidal involvement. PMID- 22084224 TI - Cutaneous halo nevi following plaque radiotherapy for uveal melanoma. PMID- 22084225 TI - Histopathologic, immunohistochemical, ultrastructural, and cytogenetic analysis of oncocytic uveal melanoma. PMID- 22084226 TI - Solitary epithelioid histiocytoma (reticulohistiocytoma) of the eyelid. PMID- 22084227 TI - Obviating endophthalmitis after cataract surgery: excellent wound closure is the key. PMID- 22084229 TI - Colobomas and amblyopia. PMID- 22084231 TI - Chloroquine and hydroxychloroquine toxicity. PMID- 22084232 TI - Proportionate topographic areas of retinal zones 1, 2, and 3 for use in describing infectious retinitis. PMID- 22084233 TI - Peripheral retinal nonperfusion in septo-optic dysplasia. PMID- 22084234 TI - Cardiac hypertrophy is positively regulated by MicroRNA miR-23a. AB - MicroRNAs (miRNAs) are a class of small noncoding RNAs that mediate post transcriptional gene silencing. Myocardial hypertrophy is frequently associated with the development of heart failure. A variety of miRNAs are involved in the regulation of cardiac hypertrophy, however, the molecular targets of miRNAs in the cardiac hypertrophic cascades remain to be fully identified. We produced miR 23a transgenic mice, and these mice exhibit exaggerated cardiac hypertrophy in response to the stimulation with phenylephrine or pressure overload by transverse aortic banding. The endogenous miR-23a is up-regulated upon treatment with phenylephrine, endothelin-1, or transverse aortic banding. Knockdown of miR-23a attenuates hypertrophic responses. To identify the downstream targets of miR-23a, we found that transcription factor Foxo3a is suppressed by miR-23a. Luciferase assay indicates that miR-23a directly inhibits the translation activity of Foxo3a 3' UTR. Introduction or knockdown of miR-23a leads to the alterations of Foxo3a protein levels. Enforced expression of the constitutively active form of Foxo3a counteracts the provocative effect of miR-23a on hypertrophy. Furthermore, we observed that miR-23a is able to alter the expression levels of manganese superoxide dismutase and the consequent reactive oxygen species, and this effect is mediated by Foxo3a. In addition, our results show that miR-23a and Foxo3a bi transgenic mice exhibit a reduced hypertrophic response compared with the miR-23a transgenic mice alone. Our present study reveals that miR-23a can mediate the hypertrophic signal through regulating Foxo3a. They form an axis in hypertrophic machinery and can be targets for the development of hypertrophic treatment. PMID- 22084235 TI - Core fucosylation of MU heavy chains regulates assembly and intracellular signaling of precursor B cell receptors. AB - alpha1,6-Fucosyltransferase (Fut8) knock-out (Fut8(-/-)) mice showed an abnormality in pre-B cell generation. Membrane assembly of pre-BCR is a crucial checkpoint for pre-B cell differentiation and proliferation in both humans and mice. The assembly of pre-BCR on the cell surface was substantially blocked in the Fut8-knockdown pre-B cell line, 70Z/3-KD cells, and then completely restored by re-introduction of the Fut8 gene to 70Z/3-KD (70Z/3-KD-re) cells. Moreover, loss of alpha1,6-fucosylation (also called core fucosylation) of MUHC was associated with the suppression of the interaction between MUHC and lambda5. In contrast to Fut8(+/+) CD19(+)CD43(-) cells, the subpopulation expressing the MUHC.lambda5 complex in the Fut8(-/-) CD19(+)CD43(-) cell fraction was decreased. The pre-BCR-mediated tyrosine phosphorylation of CD79a and activation of Btk were attenuated in Fut8-KD cells, and restored in 70Z/3-KD-re cells. The frequency of CD19(low)CD43(-) cells (pre-B cell enriched fraction) was also reduced in Fut8(-/ ) bone marrow cells, and then the levels of IgM, IgG, and IgA of 12-week-old Fut8(-/-) mice sera were significantly lower than those of Fut8(+/+) mice. Our results suggest that the core fucosylation of MUHC mediates the assembly of pre BCR to regulate pre-BCR intracellular signaling and pre-B cell proliferation. PMID- 22084236 TI - Lipocalin-2 (24p3/neutrophil gelatinase-associated lipocalin (NGAL)) receptor is expressed in distal nephron and mediates protein endocytosis. AB - In the kidney, bulk reabsorption of filtered proteins occurs in the proximal tubule via receptor-mediated endocytosis (RME) through the multiligand receptor complex megalin-cubilin. Other mechanisms and nephron sites for RME of proteins are unclear. Recently, the secreted protein 24p3 (lipocalin-2, neutrophil gelatinase-associated lipocalin (NGAL)), which is expressed in the distal nephron, has been identified as a sensitive biomarker of kidney damage. A high affinity receptor for 24p3 (24p3R) that is involved in endocytotic iron delivery has also been cloned. We investigated the localization of 24p3R in rodent kidney and its role in RME of protein-metal complexes and albumin. Immunostaining of kidney tissue showed expression of 24p3R in apical membranes of distal tubules and collecting ducts, but not of proximal tubule. The differential expression of 24p3R in these nephron segments was confirmed in the respective cell lines. CHO cells transiently transfected with 24p3R or distal tubule cells internalized submicromolar concentrations of fluorescence-coupled proteins transferrin, albumin, or metallothionein (MT) as well as the toxic cadmium-MT (Cd2+(7)-MT) complex, which caused cell death. Uptake of MT or transferrin and Cd2+(7)-MT toxicity were prevented by picomolar concentrations of 24p3. An EC50 of 123+/-50 nM was determined for binding of MT to 24p3R by microscale thermophoresis. Hence, 24p3R binds proteins filtered by the kidney with high affinity and may contribute to RME of proteins, including 24p3, and to Cd2+(7)-MT toxicity in distal nephron segments. PMID- 22084237 TI - Outer membrane lipoprotein Lpp is Gram-negative bacterial cell surface receptor for cationic antimicrobial peptides. AB - Antimicrobial peptides/proteins (AMPs) are important components of the host innate defense mechanisms. Here we demonstrate that the outer membrane lipoprotein, Lpp, of Enterobacteriaceae interacts with and promotes susceptibility to the bactericidal activities of AMPs. The oligomeric Lpp was specifically recognized by several cationic alpha-helical AMPs, including SMAP 29, CAP-18, and LL-37; AMP-mediated bactericidal activities were blocked by anti Lpp antibody blocking. Blebbing of the outer membrane and increase in membrane permeability occurred in association with the coordinate internalization of Lpp and AMP. Interestingly, the specific binding of AMP to Lpp was resistant to divalent cations and salts, which were able to inhibit the bactericidal activities of some AMPs. Furthermore, using His-tagged Lpp as a ligand, we retrieved several characterized AMPs, including SMAP-29 and hRNase 7, from a peptide library containing crude mammalian cell lysates. Overall, this study explores a new mechanism and target of antimicrobial activity and provides a novel method for screening of antimicrobials for use against drug-resistant bacteria. PMID- 22084238 TI - Intramembrane proton binding site linked to activation of bacterial pentameric ion channel. AB - Prokaryotic orthologs of eukaryotic Cys-loop receptor channels recently emerged as structural and mechanistic surrogates to investigate this superfamily of intercellular signaling proteins. Here, we examine proton activation of the prokaryotic ortholog GLIC using patch clamp electrophysiology, mutagenesis, and molecular dynamics (MD) simulations. Whole-cell current recordings from human embryonic kidney (HEK) 293 cells expressing GLIC show half-maximal activation at pH 6, close to the pK(a) of histidine, implicating the three native His residues in proton sensing linked to activation. The mutation H235F abolishes proton activation, H277Y is without effect, and all nine mutations of His-127 prevent expression on the cell surface. In the GLIC crystal structure, His-235 on transmembrane (TM) alpha-helix 2, hydrogen bonds to the main chain carbonyl oxygen of Ile-259 on TM alpha-helix 3. MD simulations show that when His-235 is protonated, the hydrogen bond persists, and the channel remains in the open conformation, whereas when His-235 is deprotonated, the hydrogen bond dissociates, and the channel closes. Mutations of the proximal Tyr-263, which also links TM alpha-helices 2 and 3 via a hydrogen bond, alter proton sensitivity over a 1.5 pH unit range. MD simulations show that mutations of Tyr-263 alter the hydrogen bonding capacity of His-235. The overall findings show that His-235 in the TM region of GLIC is a novel proton binding site linked to channel activation. PMID- 22084239 TI - Energetics of cyclic AMP binding to HCN channel C terminus reveal negative cooperativity. AB - Cyclic AMP binds to the HCN channel C terminus and variably stabilizes its open state. Using isothermal titration calorimetry, we show that cAMP binds to one subunit of tetrameric HCN2 and HCN4 C termini with high affinity (~0.12 MUM) and subsequently with low affinity (~1 MUM) to the remaining three subunits. Changes induced by high affinity binding already exist in both a constrained HCN2 tetramer and the unconstrained HCN1 tetramer. Natural "preactivation" of HCN1 may explain both the smaller effect of cAMP on stabilizing its open state and the opening of unliganded HCN1, which occurs as though already disinhibited. PMID- 22084240 TI - Nitric oxide storage and transport in cells are mediated by glutathione S transferase P1-1 and multidrug resistance protein 1 via dinitrosyl iron complexes. AB - Nitrogen monoxide (NO) plays a role in the cytotoxic mechanisms of activated macrophages against tumor cells by inducing iron release. We showed that NO mediated iron efflux from cells required glutathione (GSH) (Watts, R. N., and Richardson, D. R. (2001) J. Biol. Chem. 276, 4724-4732) and that the GSH conjugate transporter, multidrug resistance-associated protein 1 (MRP1), mediates this release potentially as a dinitrosyl-dithiol iron complex (DNIC; Watts, R. N., Hawkins, C., Ponka, P., and Richardson, D. R. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 7670-7675). Recently, glutathione S-transferase P1-1 (GST P1-1) was shown to bind DNICs as dinitrosyl-diglutathionyl iron complexes. Considering this and that GSTs and MRP1 form an integrated detoxification unit with chemotherapeutics, we assessed whether these proteins coordinately regulate storage and transport of DNICs as long lived NO intermediates. Cells transfected with GSTP1 (but not GSTA1 or GSTM1) significantly decreased NO-mediated 59Fe release from cells. This NO-mediated 59Fe efflux and the effect of GST P1-1 on preventing this were observed with NO-generating agents and also in cells transfected with inducible nitric oxide synthase. Notably, 59Fe accumulated in cells within GST P1-1-containing fractions, indicating an alteration in intracellular 59Fe distribution. Furthermore, electron paramagnetic resonance studies showed that MCF7-VP cells transfected with GSTP1 contain significantly greater levels of a unique DNIC signal. These investigations indicate that GST P1 1 acts to sequester NO as DNICs, reducing their transport out of the cell by MRP1. Cell proliferation studies demonstrated the importance of the combined effect of GST P1-1 and MRP1 in protecting cells from the cytotoxic effects of NO. Thus, the DNIC storage function of GST P1-1 and ability of MRP1 to efflux DNICs are vital in protection against NO cytotoxicity. PMID- 22084241 TI - Discovery of intracellular heme-binding protein HrtR, which controls heme efflux by the conserved HrtB-HrtA transporter in Lactococcus lactis. AB - Most commensal and food bacteria lack heme biosynthesis genes. For several of these, the capture of environmental heme is a means of activating aerobic respiration metabolism. Our previous studies in the Gram-positive bacterium Lactococcus lactis showed that heme exposure strongly induced expression of a single operon, called here hrtRBA, encoding an ortholog of the conserved membrane hrt (heme-regulated transporter) and a unique transcriptional regulator that we named HrtR. We show that HrtR expressed as a fusion protein is a heme-binding protein. Heme iron interaction with HrtR is non-covalent, hexacoordinated, and involves two histidines, His-72 and His-149. HrtR specifically binds a 15-nt palindromic sequence in the hrtRBA promoter region, which is needed for hrtRBA repression. HrtR-DNA binding is abolished by heme addition, which activates expression of the HrtB-HrtA (HrtBA) transporter in vitro and in vivo. The use of HrtR as an intracellular heme sensor appears to be conserved among numerous commensal bacteria, in contrast with numerous Gram-positive pathogens that use an extracellular heme-sensing system, HssRS, to regulate hrt. Finally, we show for the first time that HrtBA permease controls heme toxicity by its direct and specific efflux. The use of an intracellular heme sensor to control heme efflux constitutes a novel paradigm for bacterial heme homeostasis. PMID- 22084242 TI - Two-pronged binding with bromodomain-containing protein 4 liberates positive transcription elongation factor b from inactive ribonucleoprotein complexes. AB - The positive transcription elongation factor b (P-TEFb) exists in two forms in cells as follows: an inactive form where the core components cyclin T1 and CDK9 are incorporated in the 7SK small nuclear ribonucleoprotein complex containing the inhibitory molecule HEXIM1, and an active form, part of which associates with the bromodomain-containing protein BRD4. Here, we define a novel interaction between P-TEFb and BRD4 involving tri-acetylated cyclin T1 (acK380, acK386, and acK309) and the second bromodomain in BRD4. This interaction is observed with the short splice variant of BRD4 (amino acids 1-722) lacking a previously defined C terminal P-TEFb-interacting domain (PID). Notably, P-TEFb complexes associated with short BRD4 contain HEXIM1 and 7SK snRNA, implicating the PID in the liberation of P-TEFb from the 7SK small nuclear ribonucleoprotein complex (7SK snPNP). Overexpression of the PID alone in cells dissociates HEXIM1 and 7SK snRNA from P-TEFb, but it is not sufficient to activate P-TEFb-dependent transcription of the HIV LTR. Our data support a model where two BRD4 domains, the second bromodomain and the PID, bind P-TEFb and are required for full transcriptional activation of P-TEFb response genes. PMID- 22084244 TI - An electrostatic switch controls palmitoylation of the large conductance voltage- and calcium-activated potassium (BK) channel. AB - Protein palmitoylation is a major dynamic posttranslational regulator of protein function. However, mechanisms that control palmitoylation are poorly understood. In many proteins, palmitoylation occurs at cysteine residues juxtaposed to membrane-anchoring domains such as transmembrane helices, sites of irreversible lipid modification, or hydrophobic and/or polybasic domains. In particular, polybasic domains represent an attractive mechanism to dynamically control protein palmitoylation, as the function of these domains can be dramatically influenced by protein phosphorylation. Here we demonstrate that a polybasic domain immediately upstream of palmitoylated cysteine residues within an alternatively spliced insert in the C terminus of the large conductance calcium- and voltage-activated potassium channel is an important determinant of channel palmitoylation and function. Mutation of basic amino acids to acidic residues within the polybasic domain results in inhibition of channel palmitoylation and a significant right-shift in channel half maximal voltage for activation. Importantly, protein kinase A-dependent phosphorylation of a single serine residue within the core of the polybasic domain, which results in channel inhibition, also reduces channel palmitoylation. These data demonstrate the key role of the polybasic domain in controlling stress-regulated exon palmitoylation and suggests that phosphorylation controls the domain by acting as an electrostatic switch. PMID- 22084243 TI - Regulation of arginine acquisition and virulence gene expression in the human pathogen Streptococcus pneumoniae by transcription regulators ArgR1 and AhrC. AB - In this study, we investigated for the first time the transcriptional response of the human pathogen Streptococcus pneumoniae to fluctuating concentrations of arginine, an essential amino acid for this bacterium. By means of DNA microarray analyses, several operons and genes were found, the expression of which was affected by the concentration of arginine in the medium. Five of the identified operons were demonstrated to be directly repressed in the presence of high arginine concentrations via the concerted action of the ArgR-type regulators ArgR1 and AhrC. These ArgR1/AhrC targets encompass the putative amino acid transport genes artPQ, abpA, abpB, and aapA; the arginine biosynthetic genes argGH; and the virulence genes aliB and lmB/adcAII-phtD encoding an oligopeptide binding lipoprotein and cell surface Zn(2+)-scavenging units, respectively. In addition, the data indicate that three of the amino acid transport genes encode an arginine ATP-binding cassette transporter unit required for efficient growth during arginine limitation. Instead of regulating arginine biosynthetic and catabolic genes as has been reported for other Gram-positive bacteria, our findings suggest that the physiological function of ArgR1/AhrC in S. pneumoniae is to ensure optimal uptake of arginine from the surrounding milieu. PMID- 22084245 TI - Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 CRK-associated substrate. AB - Protein-tyrosine kinase 6 (PTK6) is a non-myristoylated intracellular tyrosine kinase evolutionarily related to Src kinases. Aberrant PTK6 expression and intracellular localization have been detected in human prostate tumors. In the PC3 prostate cancer cell line, the pool of endogenous activated PTK6, which is phosphorylated on tyrosine residue 342, is localized at the membrane. Expression of ectopic membrane-targeted PTK6 led to dramatic morphology changes and formation of peripheral adhesion complexes in PC3 cells. Peripheral adhesion complex formation was dependent upon PTK6 kinase activity. We demonstrated that p130 CRK-associated substrate (p130CAS) is a novel direct substrate of PTK6, and it works as a crucial adapter protein in inducing peripheral adhesion complexes. Activation of ERK5 downstream of p130CAS was indispensable for this process. Knockdown of endogenous PTK6 led to reduced cell migration and p130CAS phosphorylation, whereas knockdown of p130CAS attenuated oncogenic signaling induced by membrane-targeted PTK6, including ERK5 and AKT activation. Expression of membrane-targeted PTK6 promoted cell migration, which could be impaired by knockdown of p130CAS or ERK5. Our study reveals a novel function for PTK6 at the plasma membrane and suggests that the PTK6-p130CAS-ERK5 signaling cascade plays an important role in cancer cell migration and invasion. PMID- 22084246 TI - Hypoxia-induced acidosis uncouples the STIM-Orai calcium signaling complex. AB - The endoplasmic reticulum Ca(2+)-sensing STIM proteins mediate Ca(2+) entry signals by coupling to activate plasma membrane Orai channels. We reveal that STIM-Orai coupling is rapidly blocked by hypoxia and the ensuing decrease in cytosolic pH. In smooth muscle cells or HEK293 cells coexpressing STIM1 and Orai1, acute hypoxic conditions rapidly blocked store-operated Ca(2+) entry and the Orai1-mediated Ca(2+) release-activated Ca(2+) current (I(CRAC)). Hypoxia induced blockade of Ca(2+) entry and I(CRAC) was reversed by NH(4)(+)-induced cytosolic alkalinization. Hypoxia and acidification both blocked I(CRAC) induced by the short STIM1 Orai-activating region. Although hypoxia induced STIM1 translocation into junctions, it did not dissociate the STIM1-Orai1 complex. However, both hypoxia and cytosolic acidosis rapidly decreased Forster resonance energy transfer (FRET) between STIM1-YFP and Orai1-CFP. Thus, although hypoxia promotes STIM1 junctional accumulation, the ensuing acidification functionally uncouples the STIM1-Orai1 complex providing an important mechanism protecting cells from Ca(2+) overload under hypoxic stress conditions. PMID- 22084247 TI - CUEDC2 (CUE domain-containing 2) and SOCS3 (suppressors of cytokine signaling 3) cooperate to negatively regulate Janus kinase 1/signal transducers and activators of transcription 3 signaling. AB - Janus kinase 1/signal transducers and activators of transcription 3 (JAK1/STAT3) pathway is one of the recognized oncogenic signaling pathways that frequently overactivated in a variety of human tumors. Despite rapid progress in elucidating the molecular mechanisms of activation of JAK/STAT pathway, the processes that regulate JAK/STAT deactivation need to be further clarified. Here we demonstrate that CUE domain-containing 2 (CUEDC2) inhibits cytokine-induced phosphorylation of JAK1 and STAT3 and the subsequent STAT3 transcriptional activity. Further analysis by a yeast two-hybrid assay showed that CUEDC2 could engage in a specific interaction with a key JAK/STAT inhibitor, SOCS3 (suppressors of cytokine signaling 3). The interaction between CUEDC2 and SOCS3 is required for the inhibitory effect of CUEDC2 on JAK1 and STAT3 activity. Additionally, we found CUEDC2 functions collaboratively with SOCS3 to inhibit JAK1/STAT3 signaling by increasing SOCS3 stability via enhancing its association with Elongin C. Therefore, our findings revealed a new biological activity for CUEDC2 as the regulator of JAK1/STAT3 signaling and paved the way to a better understanding of the mechanisms by which SOCS3 has been linked to suppression of the JAK/STAT pathway. PMID- 22084248 TI - Up-regulation of the neuronal nicotinic receptor alpha7 by HIV glycoprotein 120: potential implications for HIV-associated neurocognitive disorder. AB - Approximately 30-50% of the >30 million HIV-infected subjects develop neurological complications ranging from mild symptoms to dementia. HIV does not infect neurons, and the molecular mechanisms behind HIV-associated neurocognitive decline are not understood. There are several hypotheses to explain the development of dementia in HIV(+) individuals, including neuroinflammation mediated by infected microglia and neuronal toxicity by HIV proteins. A key protein associated with the neurological complications of HIV, gp120, forms part of the viral envelope and can be found in the CSF of infected individuals. HIV-1 gp120 interacts with several receptors including CD4, CCR5, CXCR4, and nicotinic acetylcholine receptors (nAChRs). However, the role of nAChRs in HIV-associated neurocognitive disorder has not been investigated. We studied the effects of gp120(IIIB) on the expression and function of the nicotinic receptor alpha7 (alpha7-nAChR). Our results show that gp120, through activation of the CXCR4 chemokine receptor, induces a functional up-regulation of alpha7-nAChRs. Because alpha7-nAChRs have a high permeability to Ca(2+), we performed TUNEL staining to investigate the effects of receptor up-regulation on cell viability. Our data revealed an increase in cell death, which was blocked by the selective antagonist alpha-bungarotoxin. The in vitro data are supported by RT-PCR and Western blot analysis, confirming a remarkable up-regulation of the alpha7-nAChR in gp120 transgenic mice brains. Specifically, alpha7-nAChR up-regulation is observed in mouse striatum, a region severely affected in HIV(+) patients. In summary, CXCR4 activation induces up-regulation of alpha7-nAChR, causing cell death, suggesting that alpha7-nAChR is a previously unrecognized contributor to the neurotoxicity associated with HIV infection. PMID- 22084249 TI - Increasing rate of cleavage at boundary between non-structural proteins 4B and 5A inhibits replication of hepatitis C virus. AB - In hepatitis C virus, non-structural proteins are cleaved from the viral polyprotein by viral encoded proteases. Although proteolytic processing goes to completion, the rate of cleavage differs between different boundaries, primarily due to the sequence at these positions. However, it is not known whether slow cleavage is important for viral replication or a consequence of restrictions on sequences that can be tolerated at the cleaved ends of non-structural proteins. To address this question, mutations were introduced into the NS4B side of the NS4B5A boundary, and their effect on replication and polyprotein processing was examined in the context of a subgenomic replicon. Single mutations that modestly increased the rate of boundary processing were phenotypically silent, but a double mutation, which further increased the rate of boundary cleavage, was lethal. Rescue experiments relying on viral RNA polymerase-induced error failed to identify second site compensatory mutations. Use of a replicon library with codon degeneracy did allow identification of second site compensatory mutations, some of which fell exclusively within the NS5A side of the boundary. These mutations slowed boundary cleavage and only enhanced replication in the context of the original lethal NS4B double mutation. Overall, the data indicate that slow cleavage of the NS4B5A boundary is important and identify a previously unrecognized role for NS4B5A-containing precursors requiring them to exist for a minimum finite period of time. PMID- 22084250 TI - Elucidation of acid-induced unfolding and aggregation of human immunoglobulin IgG1 and IgG2 Fc. AB - Understanding the underlying mechanisms of Fc aggregation is an important prerequisite for developing stable and efficacious antibody-based therapeutics. In our study, high resolution two-dimensional nuclear magnetic resonance (NMR) was employed to probe structural changes in the IgG1 Fc. A series of (1)H-(15)N heteronuclear single-quantum correlation NMR spectra were collected between pH 2.5 and 4.7 to assess whether unfolding of C(H)2 domains precedes that of C(H)3 domains. The same pH range was subsequently screened in Fc aggregation experiments that utilized molecules of IgG1 and IgG2 subclasses with varying levels of C(H)2 glycosylation. In addition, differential scanning calorimetry data were collected over a pH range of 3-7 to assess changes in C(H)2 and C(H)3 thermostability. As a result, compelling evidence was gathered that emphasizes the importance of C(H)2 stability in determining the rate and extent of Fc aggregation. In particular, we found that Fc domains of the IgG1 subclass have a lower propensity to aggregate compared with those of the IgG2 subclass. Our data for glycosylated, partially deglycosylated, and fully deglycosylated molecules further revealed the criticality of C(H)2 glycans in modulating Fc aggregation. These findings provide important insights into the stability of Fc-based therapeutics and promote better understanding of their acid-induced aggregation process. PMID- 22084251 TI - Multiple site acetylation of Rictor stimulates mammalian target of rapamycin complex 2 (mTORC2)-dependent phosphorylation of Akt protein. AB - The serine/threonine protein kinase Akt is a critical regulator of cell growth and survival in response to growth factors. A key step in Akt activation is phosphorylation at Ser-473 by the mammalian target of rapamycin (mTOR) complex 2 (mTORC2). Although Rictor is required for the stability and activity of mTORC2, little is known about functional regions or post-translational modifications within Rictor that are responsible for regulating mTORC2. Here, we demonstrate that Rictor contains two distinct central regions critical for mTORC2 function. One we refer to as the stability region because it is critical for interaction with Sin1.1 and LST8, and a second adjacent region is required for multisite acetylation. p300-mediated acetylation of Rictor increases mTORC2 activity toward Akt, whereas site-directed mutants within the acetylation region of Rictor exhibit reduced insulin-like growth factor 1 (IGF-1)-stimulated mTORC2 kinase activity. Inhibition of deacetylases, including the NAD+-dependent sirtuins, promotes Rictor acetylation and IGF-1-mediated Akt phosphorylation. These results suggest that multiple-site acetylation of Rictor signals for increased activation of mTORC2, providing a critical link between nutrient-sensitive deacetylases and mTORC2 signaling to Akt. PMID- 22084252 TI - rNA: a fast and accurate short reads numerical aligner. AB - SUMMARY: The advent of high-throughput sequencers (HTS) introduced the need of new tools in order to analyse the large amount of data that those machines are able to produce. The mandatory first step for a wide range of analyses is the alignment of the sequences against a reference genome. We present a major update to our rNA (randomized Numerical Aligner) tool. The main feature of rNA is the fact that it achieves an accuracy greater than the majority of other tools in a feasible amount of time. rNA executables and source codes are freely downloadable at http://iga-rna.sourceforge.net/. CONTACT: vezzi@appliedgenomics.org; delfabbro@appliedgenomics.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22084253 TI - Feature-based classifiers for somatic mutation detection in tumour-normal paired sequencing data. AB - MOTIVATION: The study of cancer genomes now routinely involves using next generation sequencing technology (NGS) to profile tumours for single nucleotide variant (SNV) somatic mutations. However, surprisingly few published bioinformatics methods exist for the specific purpose of identifying somatic mutations from NGS data and existing tools are often inaccurate, yielding intolerably high false prediction rates. As such, the computational problem of accurately inferring somatic mutations from paired tumour/normal NGS data remains an unsolved challenge. RESULTS: We present the comparison of four standard supervised machine learning algorithms for the purpose of somatic SNV prediction in tumour/normal NGS experiments. To evaluate these approaches (random forest, Bayesian additive regression tree, support vector machine and logistic regression), we constructed 106 features representing 3369 candidate somatic SNVs from 48 breast cancer genomes, originally predicted with naive methods and subsequently revalidated to establish ground truth labels. We trained the classifiers on this data (consisting of 1015 true somatic mutations and 2354 non somatic mutation positions) and conducted a rigorous evaluation of these methods using a cross-validation framework and hold-out test NGS data from both exome capture and whole genome shotgun platforms. All learning algorithms employing predictive discriminative approaches with feature selection improved the predictive accuracy over standard approaches by statistically significant margins. In addition, using unsupervised clustering of the ground truth 'false positive' predictions, we noted several distinct classes and present evidence suggesting non-overlapping sources of technical artefacts illuminating important directions for future study. AVAILABILITY: Software called MutationSeq and datasets are available from http://compbio.bccrc.ca. PMID- 22084254 TI - Gene set analysis in the cloud. AB - Cloud computing offers low cost and highly flexible opportunities in bioinformatics. Its potential has already been demonstrated in high-throughput sequence data analysis. Pathway-based or gene set analysis of expression data has received relatively less attention. We developed a gene set analysis algorithm for biomarker identification in the cloud. The resulting tool, YunBe, is ready to use on Amazon Web Services. Moreover, here we compare its performance to those obtained with desktop and computing cluster solutions. AVAILABILITY AND IMPLEMENTATION: YunBe is open-source and freely accessible within the Amazon Elastic MapReduce service at s3n://lrcv-crp-sante/app/yunbe.jar. Source code and user's guidelines can be downloaded from http://tinyurl.com/yunbedownload. PMID- 22084255 TI - PubChem promiscuity: a web resource for gathering compound promiscuity data from PubChem. AB - SUMMARY: Promiscuity counts allow for a better understanding of a compound's assay activity profile and drug potential. Although PubChem contains a vast amount of compound and assay data, it currently does not have a convenient or efficient method to obtain in-depth promiscuity counts for compounds. PubChem promiscuity fills this gap. It is a Java servlet that uses NCBI Entrez (eUtils) web services to interact with PubChem and provide promiscuity counts in a variety of categories along with compound descriptors, including PAINS-based functional group detection. AVAILABILITY: http://chemutils.florida.scripps.edu/pcpromiscuity CONTACT: southern@scripps.edu PMID- 22084256 TI - Discovering transcription factor regulatory targets using gene expression and binding data. AB - MOTIVATION: Identifying the target genes regulated by transcription factors (TFs) is the most basic step in understanding gene regulation. Recent advances in high throughput sequencing technology, together with chromatin immunoprecipitation (ChIP), enable mapping TF binding sites genome wide, but it is not possible to infer function from binding alone. This is especially true in mammalian systems, where regulation often occurs through long-range enhancers in gene-rich neighborhoods, rather than proximal promoters, preventing straightforward assignment of a binding site to a target gene. RESULTS: We present EMBER (Expectation Maximization of Binding and Expression pRofiles), a method that integrates high-throughput binding data (e.g. ChIP-chip or ChIP-seq) with gene expression data (e.g. DNA microarray) via an unsupervised machine learning algorithm for inferring the gene targets of sets of TF binding sites. Genes selected are those that match overrepresented expression patterns, which can be used to provide information about multiple TF regulatory modes. We apply the method to genome-wide human breast cancer data and demonstrate that EMBER confirms a role for the TFs estrogen receptor alpha, retinoic acid receptors alpha and gamma in breast cancer development, whereas the conventional approach of assigning regulatory targets based on proximity does not. Additionally, we compare several predicted target genes from EMBER to interactions inferred previously, examine combinatorial effects of TFs on gene regulation and illustrate the ability of EMBER to discover multiple modes of regulation. AVAILABILITY: All code used for this work is available at http://dinner group.uchicago.edu/downloads.html. PMID- 22084257 TI - Where the United States falls down and how we might stand up. PMID- 22084258 TI - When lightning strikes. PMID- 22084259 TI - Impact of insurance and hospital ownership on hospital length of stay among patients with ambulatory care-sensitive conditions. AB - PURPOSE Some studies suggest proprietary (for-profit) hospitals are maximizing financial margins from patient care by limiting therapies or decreasing length of stay for uninsured patients. This study examines the role of insurance related to length of stay once the patient is in the hospital and risk for mortality, particularly in a for-profit environment. METHODS We undertook an analysis of hospitalizations in the National Hospital Discharge Survey (NHDS) of the 5-year period of 2003 to 2007 for patients aged 18 to 64 years (unweighted n = 849,866; weighted n = 90 million). The analysis included those who were hospitalized with both ambulatory care-sensitive conditions (ACSCs), hospitalizations considered to be preventable, and non-ACSCs. We analyzed the transformed mean length of stay between individuals who had Medicaid or all other insurance types while hospitalized and those who were hospitalized without insurance. This analysis was stratified by hospital ownership. We also examined the relationship between in hospital mortality and insurance status. RESULTS After controlling for comorbidities; age, sex, and race/ethnicity; and hospitalizations with either an ACSC or non-ACSC diagnosis, patients without insurance tended to have a significantly shorter length of stay. Across all hospital types, the mean length of stay for ACSCs was significantly shorter for individuals without insurance (2.77 days) than for those with either private insurance (2.89 days, P = .04) or Medicaid (3.19, P <.01). Among hospitalizations for ACSCs, in-hospital mortality rate for individuals with either private insurance or Medicaid was not significantly different from the mortality rate for those without insurance. CONCLUSIONS Patients without insurance have shorter lengths of stay for both ACSCs and non-ACSCs. Future research should examine whether patients without insurance are being discharged prematurely. PMID- 22084260 TI - Effect of closure of a local safety-net hospital on primary care physicians' perceptions of their role in patient care. AB - PURPOSE We examined how the closure of a large safety-net hospital in Los Angeles County, California, affected local primary care physicians. METHODS We conducted semistructured interviews with 42 primary care physicians who practiced in both underserved and nonunderserved settings in Los Angeles County. Two investigators independently reviewed and coded transcripts. Three investigators used pile sorting to sort the codes into themes. RESULTS Overall, 28 of 42 physicians (67%) described some effect of the hospital closure on their practices. Three major themes emerged regarding the impact of the closure on the affected physicians: (1) reduced local access to specialist consultations, direct hospital admissions, and timely emergency department evaluation; (2) more patient delays in care and worse health outcomes because of poor patient understanding of the health care system changes; and (3) loss of colleagues and opportunities to teach residents and medical students. CONCLUSIONS Physicians in close proximity to the closed hospital-even those practicing in nonunderserved settings-reported difficulty getting their patients needed care that extended beyond the anticipated loss of inpatient services. There is a need for greater recognition of and support for the role primary care physicians play in coordinating care; promoting continuity of care; and informing patients, clinic administrators and policy makers about system changes during such transitions. PMID- 22084262 TI - Trends in quality during medical home transformation. AB - PURPOSE We describe changes over time in performance on measures of technical quality and patient experience as a group of primary care clinics transformed themselves into level III patient-centered medical homes. METHODS A group of 21 Minnesota primary care clinics achieving level III recognition as medical homes by the National Committee for Quality Assurance has been tracking a variety of quality and patient satisfaction measures for years. We analyzed trends in these measures and compared them with those of other medical groups in the community to estimate what we might expect as other primary care sites gear up to achieve medical home status. RESULTS The clinics in this group achieved a 1% to 3% increase per year in patient satisfaction and a 2% to 7% increase per year in performance on quality measures for diabetes, coronary artery disease, preventive services, and generic medication use. When compared with the average for other medical groups in the region, the rates of increase were greater for satisfaction, but similar for the quality measures. CONCLUSIONS Achieving medical home recognition was associated with improvements in quality and patient satisfaction for these clinics, but the rate of improvement is slow and does not always exceed levels in the surrounding community in Minnesota (which are also improving). Expectations for large and rapid change are probably unrealistic. PMID- 22084261 TI - Parent and child usual source of care and children's receipt of health care services. AB - PURPOSE In the United States, children who have a usual source of care (USC) have better access to health care than those who do not, but little is known about how parental USC affects children's access. We examined the association between child and parent USC patterns and children's access to health care services. METHODS We undertook a secondary analysis of nationally representative, cross-sectional data from children participating in the 2002-2007 Medical Expenditure Panel Survey (n = 56,302). We assessed 10 outcome measures: insurance coverage gaps, no doctor visits in the past year, less than yearly dental visits, unmet medical and prescription needs, delayed care, problems getting care, and unmet preventive counseling needs regarding healthy eating, regular exercise, car safety devices, and bicycle helmets. RESULTS Among children, 78.6% had a USC and at least 1 parent with a USC, whereas 12.4% had a USC but no parent USC. Children with a USC but no parent USC had a higher likelihood of several unmet needs, including an insurance coverage gap (adjusted risk ratio [aRR] 1.33; 95% confidence interval [CI], 1.21-1.47), an unmet medical or prescription need (aRR 1.70; 95% CI 1.09 2.65), and no yearly dental visits (aRR 1.12; 95% CI 1.06-1.18), compared with children with a USC whose parent(s) had a USC. CONCLUSIONS Among children with a USC, having no parent USC was associated with a higher likelihood of reporting unmet needs when compared with children whose parent(s) had a USC. Policy reforms should ensure access to a USC for all family members. PMID- 22084263 TI - Complaints against family physicians submitted to disciplinary tribunals in the Netherlands: lessons for patient safety. AB - PURPOSE We analyzed the disciplinary law verdicts concerning family physicians, submitted to the Dutch disciplinary law system, to identify domains of high risk of harm for patients in family practice. METHODS The Dutch disciplinary law system offers patients the opportunity to file complaints against physicians outside a legal malpractice system, without possibility of financial compensation in case of verdicts in which the physician was found to be at fault. We performed an analysis of 250 random disciplinary law verdicts on Dutch family physicians submitted to disciplinary tribunals and published between 2008 and 2010. Our analysis focused on clinical domains represented in the verdicts with serious permanent damage or death. RESULTS Of the 74 complaints with a serious health outcome, 44.6% (n = 33) were related to a wrong diagnosis, 23.0% (n = 17) to insufficient care, 8.1% (n = 6) to a wrong treatment, 8.1% (n = 6) to a late arrival at a house visit, 5.4% (n = 4) to a late referral to the hospital, and 1.4% (n = 1) to insufficient information given; 9.5% (n = 7) consisted of other complaints. The wrong or late diagnosis-related cases mostly consisted of myocardial infarction and stroke (35.1%) and malignancies (33.7%). The family physician was disciplined as a result of 37 of these 74 complaints (50%). Logistic regression analysis showed that a serious outcome was associated with a higher probability of disciplinary measures (B=0.703; P =.02) CONCLUSIONS The disciplinary law system in the Netherlands differs fundamentally from a legal malpractice system. It can be used to learn from patients' complaints with a view on improving patient safety. PMID- 22084264 TI - Translating cholesterol guidelines into primary care practice: a multimodal cluster randomized trial. AB - PURPOSE We wanted to determine whether an intervention based on patient activation and a physician decision support tool was more effective than usual care for improving adherence to National Cholesterol Education Program guidelines. METHODS A 1-year cluster randomized controlled trial was performed using 30 primary care practices (4,105 patients) in southeastern New England. The main outcome was the percentage of patients screened for hyperlipidemia and treated to their low-density lipoprotein (LDL) and non-high-density lipoprotein (HDL) cholesterol goals. RESULTS After 1 year of intervention, both randomized practice groups improved screening (89% screened), and 74% of patients in both groups were at their LDL and non-HDL cholesterol goals (P <.001). Using intent-to treat analysis, we found no statistically significant differences between practice groups in screening or percentage of patients who achieved LDL and non HDL cholesterol goals. Post hoc analysis showed practices who made high use of the patient activation kiosk were more likely to have patients screened (odds ratio [OR] = 2.54; 95% confidence interval [CI], 1.97-3.27) compared with those who made infrequent or no use. Additionally, physicians who made high use of decision support tools were more likely to have their patients at their LDL cholesterol goals (OR = 1.27; 95% CI, 1.07-1.50) and non-HDL goals (OR = 1.23; 95% CI, 1.04-1.46) than low-use or no-use physicians. CONCLUSION This study showed null results with the intent-to-treat analysis regarding the benefits of a patient activation and a decision support tool in improving cholesterol management in primary care practices. Post hoc analysis showed a potential benefit in practices that used the e-health tools more frequently in screening and management of dyslipidemia. Further research on how to incorporate and increase adoption of user-friendly, patient-centered e-health tools to improve screening and management of chronic diseases and their risk factors is warranted. PMID- 22084266 TI - Promoting healthy lifestyles and decreasing childhood obesity: increasing physician effectiveness through advocacy. AB - Childhood obesity is a well-documented public health crisis. Even many children who are not overweight have inadequate physical activity, poor nutrition, excessive television and other screen time, or some combination thereof. The solution lies in the community. Environmental interventions are among the most effective for improving public health. In addition to addressing lifestyle issues in the office, physicians should advocate for environmental approaches. We can advocate at institutional, local, state, and federal levels through speaking, writing, and collaborating with others. In the United States, the timing is right to synergize with efforts such as the White House Task Force on Childhood Obesity and the Surgeon General's emphasis on changing the national conversation "from a negative one about obesity and illness" to a positive one about health and fitness. PMID- 22084265 TI - Patient-doctor depth-of-relationship scale: development and validation. AB - PURPOSE Because patient-doctor continuity has been measured in its longitudinal rather than its personal dimension, evidence to show that seeing the same doctor leads to better patient care is weak. Existing relational measures of patient doctor continuity are limited, so we developed a new patient self-completion instrument designed to specifically measure patient-doctor depth of relationship. METHODS Draft versions of the questionnaire were tested with patients in face-to face interviews and 2 rounds of pilot testing. The final instrument was completed by patients attending routine appointments with their general practitioner, and some were sent a follow-up questionnaire. Scale structure, validity, and reliability were assessed. RESULTS Face validity of candidate items was confirmed in interviews with 11 patients. Data from the pilot rounds 1 (n = 375) and 2 (n = 154) were used to refine and shorten the questionnaire. The final instrument comprised a single scale of 8 items and had good internal reliability (Cronbach's alpha = .93). In the main study (N = 490), seeing the same doctor was associated with deep patient-doctor relationships, but the relationship appeared to be nonlinear (overall adjusted odds ratio = 1.5; 95% CI, 1.2-1.8). Test-retest reliability in a sample of participants (n = 154) was good (intracluster correlation coefficient 0.87; 95% CI, 0.53-0.97). CONCLUSIONS The Patient-Doctor Depth-of-Relationship Scale is a novel, conceptually grounded questionnaire that is easy for patients to complete and is psychometrically robust. Future research will further establish its validity and answer whether patient-doctor depth of relationship is associated with improved patient care. PMID- 22084267 TI - Family physicians leaving their clinic--the Balint group as an opportunity to say good-bye. AB - The cornerstone of family medicine is the belief in both the continuity and availability of care. These beliefs are challenged when a doctor leaves his or her clinic because of personal reasons. In the example described in this article, the involvement of colleagues in a Balint group led a doctor to a flash insight into her conflicting feelings related to leaving her clinic. The group process helped her to prepare and deal with her own feelings and needs, as well as those of her patients and staff. Balint groups are a secure place to explore and gain insight into the emotional aspects of attachment and separation of physicians from their patients. PMID- 22084268 TI - AAFP's new president urges family physicians to "be part of the unstoppable force of family medicine". PMID- 22084269 TI - Pisacano Leadership Foundation names 2011 Pisacano Scholars. PMID- 22084270 TI - Building a high-performance organization for the discipline. PMID- 22084271 TI - Leadership in an age of uncertainty and austerity. PMID- 22084272 TI - Implications of the 2011 ACGME duty hour rules. PMID- 22084273 TI - Lessons learned from rebuilding a primary care infrastructure: a Canadian perspective. PMID- 22084276 TI - POLG-related disorders: defects of the nuclear and mitochondrial genome interaction. PMID- 22084277 TI - Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. PMID- 22084278 TI - SPP1 genotype is a determinant of disease severity in Duchenne muscular dystrophy: predicting the severity of Duchenne muscular dystrophy: implications for treatment. PMID- 22084279 TI - The outer arterial wall layers are primarily affected in spontaneous cervical artery dissection. PMID- 22084280 TI - Teaching NeuroImages: apathetic variant of frontotemporal dementia. PMID- 22084281 TI - Teaching NeuroImages: perineural spread of basal cell carcinoma along the trigeminal nerve. PMID- 22084282 TI - Teaching NeuroImages: recurrent vertebrobasilar embolism out of a blind sack. PMID- 22084283 TI - Reduced uptake of [18F]FDOPA PET in asymptomatic welders with occupational manganese exposure. PMID- 22084284 TI - A new golden age: testing general relativity with cosmology. AB - Gravity drives the evolution of the Universe and is at the heart of its complexity. Einstein's field equations can be used to work out the detailed dynamics of space and time and to calculate the emergence of large-scale structure in the distribution of galaxies and radiation. Over the past few years, it has become clear that cosmological observations can be used not only to constrain different world models within the context of Einstein gravity but also to constrain the theory of gravity itself. In this article, we look at different aspects of this new field in which cosmology is used to test theories of gravity with a wide range of observations. PMID- 22084285 TI - One gravitational potential or two? Forecasts and tests. AB - The metric of a perturbed Robertson-Walker space-time is characterized by three functions: a scale-factor giving the expansion history and two potentials that generalize the single potential of Newtonian gravity. The Newtonian potential induces peculiar velocities and, from these, the growth of matter fluctuations. Massless particles respond equally to the Newtonian potential and to a curvature potential. The difference of the two potentials, called the gravitational slip, is predicted to be very small in general relativity, but can be substantial in modified gravity theories. The two potentials can be measured, and gravity tested on cosmological scales, by combining weak gravitational lensing or the integrated Sachs-Wolfe effect with galaxy peculiar velocities or clustering. PMID- 22084286 TI - Modifications of gravity. AB - General relativity (GR) is a phenomenologically successful theory that rests on firm foundations, but has not been tested on cosmological scales. The deep mystery of dark energy (and possibly even the requirement of cold dark matter (CDM)) has increased the need for testing modifications to GR, as the inference of such otherwise undetected fluids depends crucially on the theory of gravity. Here, I discuss a general scheme for constructing consistent and covariant modifications to the Einstein equations. This framework is such that there is a clear connection between the modification and the underlying field content that produces it. I argue that this is mandatory for distinguishing modifications of gravity from conventional fluids. I give a non-trivial example, a simple metric based modification of the fluctuation equations for which the background is exact LambdaCDM, but differs from it in the perturbations. I show how this can be generalized and solved in terms of two arbitrary functions. Finally, I discuss future prospects and directions of research. PMID- 22084287 TI - Constraints on gravity on cosmic scales with upcoming large-scale structure surveys. AB - We consider how upcoming, prospective large-scale structure surveys, measuring galaxy weak lensing and position in tandem with the cosmic microwave background temperature anisotropies, constrain cosmic scale modifications to general relativity. In such theories, both the homogeneous expansion history and the growth of large-scale structure can have signatures of the modification. We consider an equation of state figure of merit parameter, and introduce an analogous figure of merit parameter for modified gravity, to quantify the relative constraints. We discuss how assumptions about the presence of astrophysical and instrumental systematics such as galaxy bias, intrinsic alignments, weak lensing shear calibration uncertainties and photometric redshift offsets can impact the prospective dark energy constraints. PMID- 22084288 TI - Model-independent tests of cosmic gravity. AB - Gravitation governs the expansion and fate of the universe, and the growth of large-scale structure within it, but has not been tested in detail on these cosmic scales. The observed acceleration of the expansion may provide signs of gravitational laws beyond general relativity (GR). Since the form of any such extension is not clear, from either theory or data, we adopt a model-independent approach to parametrizing deviations to the Einstein framework. We explore the phase space dynamics of two key post-GR functions and derive a classification scheme, and an absolute criterion on accuracy necessary for distinguishing classes of gravity models. Future surveys will be able to constrain the post-GR functions' amplitudes and forms to the required precision, and hence reveal new aspects of gravitation. PMID- 22084289 TI - A gravitational puzzle. AB - The challenge to understand the physical origin of the cosmic acceleration is framed as a problem of gravitation. Specifically, does the relationship between stress-energy and space-time curvature differ on large scales from the predictions of general relativity. In this article, we describe efforts to model and test a generalized relationship between the matter and the metric using cosmological observations. Late-time tracers of large-scale structure, including the cosmic microwave background, weak gravitational lensing, and clustering are shown to provide good tests of the proposed solution. Current data are very close to proving a critical test, leaving only a small window in parameter space in the case that the generalized relationship is scale free above galactic scales. PMID- 22084290 TI - Tensor-vector-scalar-modified gravity: from small scale to cosmology. AB - The impressive success of the standard cosmological model has suggested to many that its ingredients are all that one needs to explain galaxies and their systems. I summarize a number of known problems with this programme. They might signal the failure of standard gravity theory on galaxy scales. The requisite hints as to the alternative gravity theory may lie with the modified Newtonian dynamics (MOND) paradigm, which has proved to be an effective summary of galaxy phenomenology. A simple nonlinear modified gravity theory does justice to MOND at the non-relativistic level, but cannot be consistently promoted to relativistic status. The obstacles were first side-stepped with the formulation of tensor vector-scalar theory (TeVeS), a covariant-modified gravity theory. I review its structure, its MOND and Newtonian limits, and its performance in the face of galaxy phenomenology. I also summarize features of TeVeS cosmology and describe the confrontation with data from strong and weak gravitational lensing. PMID- 22084291 TI - Modifying gravity: you cannot always get what you want. AB - The combination of general relativity (GR) and the Standard Model of particle physics disagrees with numerous observations on scales from our Solar System up. In the canonical concordance model of Lambda cold dark matter (LambdaCDM) cosmology, many of these contradictions between theory and data are removed or alleviated by the introduction of three completely independent new components of stress energy--the inflaton, dark matter and dark energy. Each of these in its turn is meant to have dominated (or to currently dominate) the dynamics of the Universe. There is, until now, no non-gravitational evidence for any of these dark sectors, nor is there evidence (though there may be motivation) for the required extension of the Standard Model. An alternative is to imagine that it is GR that must be modified to account for some or all of these disagreements. Certain coincidences of scale even suggest that one might expect not to make independent modifications of the theory to replace each of the three dark sectors. Because they must address the most different types of data, attempts to replace dark matter with modified gravity are the most controversial. A phenomenological model (or family of models), modified Newtonian dynamics, has, over the last few years, seen several covariant realizations. We discuss a number of challenges that any model that seeks to replace dark matter with modified gravity must face: the loss of Birkhoff's theorem, and the calculational simplifications it implies; the failure to explain clusters, whether static or interacting, and the consequent need to introduce dark matter of some form, whether hot dark matter neutrinos or dark fields that arise in new sectors of the modified gravity theory; the intrusion of cosmological expansion into the modified force law, which arises precisely because of the coincidence in scale between the centripetal acceleration at which Newtonian gravity fails in galaxies and the cosmic acceleration. We conclude with the observation that, although modified gravity may indeed manage to replace dark matter, it is likely to do so by becoming or at least incorporating a dark matter theory itself. PMID- 22084292 TI - Testing general relativity: from local to cosmological scales. AB - I summarize various tests of general relativity on astrophysical scales, based on the large-scale structure of the universe but also on other systems, in particular the constants of physics. I emphasize the importance of hypotheses on the geometric structures of our universe while performing such tests and discuss their complementarity as well as their possible extensions. PMID- 22084293 TI - Redshift-space distortions. AB - Comparing measurements of redshift-space distortions (RSDs) with geometrical observations of the expansion of the Universe offers tremendous potential for testing general relativity on very large scales. The basic linear theory of RSDs in the distant-observer limit has been known for 25 years and the effect has been conclusively observed in numerous galaxy surveys. The next generation of galaxy survey will observe many millions of galaxies over volumes of many tens of Gpc(3). They will provide RSD measurements of such exquisite precision that we will have to carefully analyse and correct for many systematic deviations from this simple picture in order to fully exploit the statistical precision obtained. We review RSD theory and show how ubiquitous RSDs actually are, and then consider a number of potential systematic effects, shamelessly highlighting recent work in which we have been involved. This review ends by looking ahead to the future surveys that will make the next generation of RSD measurements. PMID- 22084294 TI - Cosmological probes of modified gravity: the nonlinear regime. AB - We review the effects of modified gravity on large-scale structure in the nonlinear regime, focusing on f(R) gravity and the Dvali-Gabadadze-Porrati model, for which full N-body simulations have been performed. In particular, we discuss the abundance of massive halos, the nonlinear matter power spectrum and the dynamics within clusters and galaxies, with particular emphasis on the screening mechanisms present in these models. PMID- 22084295 TI - Designing surveys for tests of gravity. AB - Modified gravity theories may provide an alternative to dark energy to explain cosmic acceleration. We argue that the observational programme developed to test dark energy needs to be augmented to capture new tests of gravity on astrophysical scales. Several distinct signatures of gravity theories exist outside the 'linear' regime, especially owing to the screening mechanism that operates inside halos such as the Milky Way to ensure that gravity tests in the solar system are satisfied. This opens up several decades in length scale and classes of galaxies at low redshift that can be exploited by surveys. While theoretical work on models of gravity is in the early stages, we can already identify new regimes that cosmological surveys could target to test gravity. These include: (i) a small-scale component that focuses on the interior and vicinity of galaxy and cluster halos, (ii) spectroscopy of low-redshift galaxies, especially galaxies smaller than the Milky Way, in environments that range from voids to clusters, and (iii) a programme of combining lensing and dynamical information, from imaging and spectroscopic surveys, respectively, on the same (or statistically identical) sample of galaxies. PMID- 22084296 TI - Model selection for modified gravity. AB - In this article, we review model selection predictions for modified gravity scenarios as an explanation for the observed acceleration of the expansion history of the Universe. We present analytical procedures for calculating expected Bayesian evidence values in two cases: (i) that modified gravity is a simple parametrized extension of general relativity (GR; two nested models), such that a Bayes' factor can be calculated, and (ii) that we have a class of non nested models where a rank-ordering of evidence values is required. We show that, in the case of a minimal modified gravity parametrization, we can expect large area photometric and spectroscopic surveys, using three-dimensional cosmic shear and baryonic acoustic oscillations, to 'decisively' distinguish modified gravity models over GR (or vice versa), with odds of ?1:100. It is apparent that the potential discovery space for modified gravity models is large, even in a simple extension to gravity models, where Newton's constant G is allowed to vary as a function of time and length scale. On the time and length scales where dark energy dominates, it is only through large-scale cosmological experiments that we can hope to understand the nature of gravity. PMID- 22084297 TI - What do we really know about dark energy? AB - In this paper, we discuss what we truly know about dark energy. I shall argue that, to date, our single indication for the existence of dark energy comes from distance measurements and their relation to redshift. Supernovae, cosmic microwave background anisotropies and observations of baryon acoustic oscillations simply tell us that the observed distance to a given redshift z is larger than the one expected from a Friedmann-Lemaitre universe with matter only and the locally measured Hubble parameter. PMID- 22084298 TI - Is the Universe homogeneous? AB - The standard model of cosmology is based on the existence of homogeneous surfaces as the background arena for structure formation. Homogeneity underpins both general relativistic and modified gravity models and is central to the way in which we interpret observations of the cosmic microwave background (CMB) and the galaxy distribution. However, homogeneity cannot be directly observed in the galaxy distribution or CMB, even with perfect observations, since we observe on the past light cone and not on spatial surfaces. We can directly observe and test for isotropy, but to link this to homogeneity we need to assume the Copernican principle (CP). First, we discuss the link between isotropic observations on the past light cone and isotropic space-time geometry: what observations do we need to be isotropic in order to deduce space-time isotropy? Second, we discuss what we can say with the Copernican assumption. The most powerful result is based on the CMB: the vanishing of the dipole, quadrupole and octupole of the CMB is sufficient to impose homogeneity. Real observations lead to near-isotropy on large scales--does this lead to near-homogeneity? There are important partial results, and we discuss why this remains a difficult open question. Thus, we are currently unable to prove homogeneity of the Universe on large scales, even with the CP. However, we can use observations of the cosmic microwave background, galaxies and clusters to test homogeneity itself. PMID- 22084299 TI - Confirmation of the Copernican principle through the anisotropic kinetic Sunyaev Zel'dovich effect. AB - The Copernican principle remains largely unproven at Gpc radial scale and above. Generally, violations of this type cause a first-order anisotropic kinetic Sunyaev Zel'dovich (kSZ) effect. Here we show that, if large-scale radial inhomogeneities have amplitude large enough to explain the 'dark energy' phenomena, the induced kSZ power spectrum will be orders of magnitude larger than the Atacama cosmology telescope/South Pole telescope upper limit. This single test rules out the void model as the cause of the apparent cosmic acceleration, confirms the Copernican principle on Gpc radial scale and above, and closes a loophole in the standard cosmology. PMID- 22084300 TI - Arrhythmia-induced cardiomyopathies: the riddle of the chicken and the egg still unanswered? AB - The hypothesis testing of inappropriate fast, irregular, or asynchronous myocardial contraction provoking cardiomyopathy has been the primary focus of numerous research efforts, especially during the last few decades. Rapid ventricular rates resulting from supraventricular arrhythmias and atrial fibrillation (AF), irregularity of heart rhythm-basic element of AF-and asynchrony, as a consequence of right ventricular pacing, bundle branch block, or frequent premature ventricular complexes, have been established as primary causes of arrhythmia-induced cardiomyopathy. The main pathophysiological pathways involved have been clarified, including neurohumoral activation, energy stores depletion, and abnormalities in stress and strain. Unfortunately, from a clinical point of view, patients usually seek medical advice only when symptoms develop, while the causative arrhythmia may be present for months or years, resulting in myocardial remodelling, diastolic, and systolic dysfunction. In some cases, making a definite diagnosis may become a strenuous exercise for the treating physician, as the arrhythmia may not be present and, additionally, therapy must be applied for the diagnosis to be confirmed retrospectively. The diagnostic process is also hardened due to the fact that strict diagnosing criteria are still a matter of discrepancy. Therapy options include pharmaceutical agents trials, catheter-based therapies and, in the context of chronic ventricular pacing, resynchronization. For the majority of patients, partial or complete recovery is expected, although they have to be followed up thoroughly due to the risk of recurrence. Large, randomized controlled trials are more than necessary to optimize patients' stratification and therapeutic strategy choices. PMID- 22084301 TI - Doubly robust estimation of the generalized impact fraction. AB - The attributable fraction (AF) is commonly used in epidemiology to quantify the impact of an exposure to a disease. Recently, Sjolander and Vansteelandt (2011. Doubly robust estimation of attributable fractions. Biostatistics 12, 112-121) introduced the doubly robust (DR) estimator of the AF, which involves positing models for both the exposure and the outcome and is consistent if at least one of these models is correct. In this article, we derived a DR estimator of the generalized impact fraction (IF) with a polytomous exposure. The IF is a measure that generalizes the AF by allowing the possibility of incomplete removal of the exposure. We demonstrated the performance of the proposed estimator via a simulation study and by application to data from a large prospective cohort study conducted in Japan. PMID- 22084302 TI - Gene-environment interaction testing in family-based association studies with phenotypically ascertained samples: a causal inference approach. AB - We propose a method for testing gene-environment (G * E) interactions on a complex trait in family-based studies in which a phenotypic ascertainment criterion has been imposed. This novel approach employs G-estimation, a semiparametric estimation technique from the causal inference literature, to avoid modeling of the association between the environmental exposure and the phenotype, to gain robustness against unmeasured confounding due to population substructure, and to acknowledge the ascertainment conditions. The proposed test allows for incomplete parental genotypes. It is compared by simulation studies to an analogous conditional likelihood-based approach and to the QBAT-I test, which also invokes the G-estimation principle but ignores ascertainment. We apply our approach to a study of chronic obstructive pulmonary disorder. PMID- 22084303 TI - Denise Montell: lighting the way in border cell migration by Caitlin Sedwick. PMID- 22084304 TI - The secret life of alpha-catenin: moonlighting in morphogenesis. AB - Cadherin-based intercellular adhesions are important determinants of proper tissue architecture. These adhesions must be both stable and dynamic to maintain tissue integrity as cells undergo morphogenetic movements during development. The role of alpha-catenin in this process has been vigorously debated due to conflicting in vitro and in vivo evidence regarding its molecular mechanism of action. Recent data supports the classical view that alpha-catenin facilitates actin attachments at adherens junctions, but also suggests that alpha-catenin may act as a force transducer, and may have additional roles in the cytoplasm. These multiple functions for alpha-catenin converge on the regulation of adhesion and may help to explain its stable yet dynamic nature. PMID- 22084305 TI - The Rap1-Rgl-Ral signaling network regulates neuroblast cortical polarity and spindle orientation. AB - A crucial first step in asymmetric cell division is to establish an axis of cell polarity along which the mitotic spindle aligns. Drosophila melanogaster neural stem cells, called neuroblasts (NBs), divide asymmetrically through intrinsic polarity cues, which regulate spindle orientation and cortical polarity. In this paper, we show that the Ras-like small guanosine triphosphatase Rap1 signals through the Ral guanine nucleotide exchange factor Rgl and the PDZ protein Canoe (Cno; AF-6/Afadin in vertebrates) to modulate the NB division axis and its apicobasal cortical polarity. Rap1 is slightly enriched at the apical pole of metaphase/anaphase NBs and was found in a complex with atypical protein kinase C and Par6 in vivo. Loss of function and gain of function of Rap1, Rgl, and Ral proteins disrupt the mitotic axis orientation, the localization of Cno and Mushroom body defect, and the localization of cell fate determinants. We propose that the Rap1-Rgl-Ral signaling network is a novel mechanism that cooperates with other intrinsic polarity cues to modulate asymmetric NB division. PMID- 22084306 TI - CENP-A exceeds microtubule attachment sites in centromere clusters of both budding and fission yeast. AB - The stoichiometries of kinetochores and their constituent proteins in yeast and vertebrate cells were determined using the histone H3 variant CENP-A, known as Cse4 in budding yeast, as a counting standard. One Cse4-containing nucleosome exists in the centromere (CEN) of each chromosome, so it has been assumed that each anaphase CEN/kinetochore cluster contains 32 Cse4 molecules. We report that anaphase CEN clusters instead contained approximately fourfold more Cse4 in Saccharomyces cerevisiae and ~40-fold more CENP-A (Cnp1) in Schizosaccharomyces pombe than predicted. These results suggest that the number of CENP-A molecules exceeds the number of kinetochore-microtubule (MT) attachment sites on each chromosome and that CENP-A is not the sole determinant of kinetochore assembly sites in either yeast. In addition, we show that fission yeast has enough Dam1 DASH complex for ring formation around attached MTs. The results of this study suggest the need for significant revision of existing CEN/kinetochore architectural models. PMID- 22084307 TI - Point centromeres contain more than a single centromere-specific Cse4 (CENP-A) nucleosome. AB - Cse4 is the budding yeast homologue of CENP-A, a modified histone H3 that specifies the base of kinetochores in all eukaryotes. Budding yeast is unique in having only one kinetochore microtubule attachment site per centromere. The centromere is specified by CEN DNA, a sequence-specific binding complex (CBF3), and a Cse4-containing nucleosome. Here we compare the ratio of kinetochore proximal Cse4-GFP fluorescence at anaphase to several standards including purified EGFP molecules in vitro to generate a calibration curve for the copy number of GFP-fusion proteins. Our results yield a mean of ~5 Cse4s, ~3 inner kinetochore CBF3 complexes, and ~20 outer kinetochore Ndc80 complexes. Our calibrated measurements increase 2.5-3-fold protein copy numbers at eukaryotic kinetochores based on previous ratio measurements assuming two Cse4s per budding yeast kinetochore. All approximately five Cse4s may be associated with the CEN nucleosome, but we show that a mean of three Cse4s could be located within flanking nucleosomes at random sites that differ between chromosomes. PMID- 22084308 TI - Sticky/Citron kinase maintains proper RhoA localization at the cleavage site during cytokinesis. AB - In many organisms, the small guanosine triphosphatase RhoA controls assembly and contraction of the actomyosin ring during cytokinesis by activating different effectors. Although the role of some RhoA effectors like formins and Rho kinase is reasonably understood, the functions of another putative effector, Citron kinase (CIT-K), are still debated. In this paper, we show that, contrary to previous models, the Drosophila melanogaster CIT-K orthologue Sticky (Sti) does not require interaction with RhoA to localize to the cleavage site. Instead, RhoA fails to form a compact ring in late cytokinesis after Sti depletion, and this function requires Sti kinase activity. Moreover, we found that the Sti Citron Nik1 homology domain interacts with RhoA regardless of its status, indicating that Sti is not a canonical RhoA effector. Finally, Sti depletion caused an increase of phosphorylated myosin regulatory light chain at the cleavage site in late cytokinesis. We propose that Sti/CIT-K maintains correct RhoA localization at the cleavage site, which is necessary for proper RhoA activity and contractile ring dynamics. PMID- 22084310 TI - Astrocyte pVHL and HIF-alpha isoforms are required for embryonic-to-adult vascular transition in the eye. AB - Successful transition from embryonic to adult circulation is critical for survival of mammalian organisms. This shift occurs in the central cardiovascular circulation and in the eye as oxygen tension increases. However, its regulation is not well understood. We have used combinatorial gene deletion and overexpression assays to assess the effect of astrocyte-targeted deletion of von Hippel-Lindau tumor suppressor (Vhl), hypoxia-inducible factor-alphas (Hif alphas), and Vegf on the normal regression of the hyaloidal vessels, the fetal ocular circulation system. Astrocytic Vhl deletion induced accelerated hyaloidal regression and subsequent massive secondary outgrowth. Combinatorial gene deletion involving Vhl, Hif-alphas, and Vegf genes revealed that HIF 2alpha/vascular endothelial growth factor signaling induces secondary outgrowth in Vhl mutants. Conversely, HIF-1alpha regulated macrophage migration inhibitory factor and promoted macrophage infiltration that accelerates hyaloidal vessel regression. The phenotype observed in Vhl mutants strongly resembles human persistent hyperplastic primary vitreous cases and may provide insights into vascular remodeling mechanisms in other systems. PMID- 22084309 TI - Two single-headed myosin V motors bound to a tetrameric adapter protein form a processive complex. AB - Myo4p, one of two class V myosins in budding yeast, continuously transports messenger RNA (mRNA) cargo in the cell but is nonprocessive when characterized in vitro. The adapter protein She3p tightly binds to the Myo4p rod, forming a single headed motor complex. In this paper, we show that two Myo4p-She3p motors are recruited by the tetrameric mRNA-binding protein She2p to form a processive double-headed complex. The binding site for She3p was mapped to a single alpha helix that protrudes at right angles from She2p. Processive runs of several micrometers on yeast actin-tropomyosin filaments were observed only in the presence of She2p, and, thus, motor activity is regulated by cargo binding. While moving processively, each head steps ~72 nm in a hand-over-hand motion. Coupling two high-duty cycle monomeric motors via a common cargo-binding adapter protein creates a complex with transport properties comparable with a single dimeric processive motor such as vertebrate myosin Va. PMID- 22084311 TI - Blood and body fluid exposures in the French military. AB - BACKGROUND: Occupational exposure to blood and body fluids (BBFs) is a hazard of many occupations, particularly hospital-based health care providers. However, non hospital-based health care workers (HCWs) and other personnel not providing health care are also at risk. AIMS: To present the results of surveillance of accidental exposure to BBFs among non-hospital-based French military personnel between 2007 and 2009, comparing different occupational categories. METHODS: The study population included all French military personnel subjected to occupational BBF exposure in a non-hospital setting. BBF exposure was defined as any percutaneous (needlestick injury, scalpel cut, etc.) or mucocutaneous (splash to mucosa, eyes or non-intact skin) exposure to blood, a biological fluid contaminated with blood or a fluid known to transmit blood-borne pathogens. RESULTS: Between 1 January 2007 and 31 December 2009, 704 occupational BBF exposures were reported in non-hospital-based French military personnel. Annualized BBF exposure incidence rates were statistically different among health care workers in non-hospital settings, firefighters, 'gendarmes' and other military personnel, with respectively 38.7, 5.4, 0.8 and 0.1 exposures per 1000 persons per year. Among the 97 cases of HIV post-exposure prophylaxis (PEP) initiated, the source patient's HIV status was unknown in 78 cases (84%). CONCLUSIONS: These results suggest that the appropriateness of HIV PEP initiation in the French military should be reviewed. Adapting French guidelines for managing BBF exposure, for non-hospital-based environments should be considered. PMID- 22084312 TI - A functional variant in the core promoter of the CD95 cell death receptor gene predicts prognosis in acute promyelocytic leukemia. AB - Up to 15% of acute promyelocytic leukemia (APL) patients fail to achieve or maintain remission. We investigated a common G > A polymorphism at position -1377 (rs2234767) in the core promoter of the CD95 cell death receptor gene in 708 subjects with acute myeloid leukemia, including 231 patients with APL. Compared with the GG genotype, carrier status for the -1377A variant was associated with a significantly worse prognosis in APL patients. Carriers were more likely to fail remission induction (odds ratio = 4.22; 95% confidence interval, 1.41-12.6, P = .01), were more likely to die during the first 8 weeks of remission induction therapy (hazard ratio = 7.26; 95% confidence interval, 2.39-22.9, P = .0005), and had a significantly worse 5-year overall survival (odds ratio = 2.14; 95% confidence interval, 1.10-4.15, P = .03). The -1377A variant destroys a binding site for the SP1 transcriptional regulator and is associated with lower transcriptional activity of the CD95 promoter. Identifying patients at high risk of life-threatening events, such as remission induction failure, is a high priority in APL, especially because such events represent a major cause of death despite the introduction of differentiation therapy. PMID- 22084313 TI - Functional CSF-1 receptors are located at the nuclear envelope and activated via the p110delta isoform of PI 3-kinase. AB - Colony stimulating factor-1 (CSF-1) and its receptor (CSF-1R) are key regulators of macrophage biology, and their elevated expression in cancer cells has been linked to poor prognosis. CSF-1Rs are thought to function at the plasma membrane. We show here that functional CSF-1Rs are present at the nuclear envelope of various cell types, including primary macrophages, human cancer cell lines, and primary human carcinomas. In response to CSF-1, added to intact cells or isolated nuclei, nucleus-associated CSF-1R became phosphorylated and triggered the phosphorylation of Akt and p27 inside the nucleus. Extracellularly added CSF-1 was also found to colocalize with nucleus-associated CSF-1Rs. All these activities were found to depend selectively on the activity of the p110delta isoform of phosphoinositide 3-kinase (PI3K). This finding was related to the p110delta-dependent translocation of exogenous CSF-1 to the nucleus-associated CSF-1Rs, correlating with a prominent role of p110delta in activation of the Rab5 GTPase, a key regulator of the endocytic trafficking. siRNA-silencing of Rab5a phenocopied p110delta inactivation and nuclear CSF-1 signaling. Our work demonstrates for the first time the presence of functional nucleus-associated CSF 1Rs, which are activated by extracellular CSF-1 by a mechanism that involves p110delta and Rab5 activity. These findings may have important implications in cancer development. PMID- 22084314 TI - A rice transmembrane bZIP transcription factor, OsbZIP39, regulates the endoplasmic reticulum stress response. AB - The endoplasmic reticulum (ER) responds to the accumulation of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways. These pathways are known as the ER stress response or the unfolded protein response. In this study, three rice basic leucine zipper (bZIP) transcription factors (OsbZIP39, OsbZIP50 and OsbZIP60) containing putative transmembrane domains (TMDs) in their C-terminal regions were identified as candidates of the ER stress sensor transducer. One of these proteins, OsbZIP39, was characterized in this study. OsbZIP39 was shown to associate with microsomes as a membrane-integrated protein using the subcellular fractionation method. When the full length and a truncated form of OsbZIP39 without the TMD (OsbZIP39DeltaC) was fused to green fluorescent protein (GFP) and transfected into rice protoplasts, the proteins were identified in the cytoplasm and nucleus, respectively. This suggests that OsbZIP39 may be converted into a soluble truncated form by proteolytic cleavage and subsequently translocated to the nucleus. Expression of OsbZIP39DeltaC clearly activated the binding protein 1 (BiP1) promoter in a rice protoplast transient assay. Overexpression of OsbZIP39DeltaC in stable transgenic rice also led to the up-regulation of several ER stress response genes including BiP1 and OsbZIP50 in the absence of ER stress. However, in the OsbZIP39DeltaC-overexpressing line, OsbZIP50 mRNA did not undergo IRE1 (inositol-requiring protein 1)-mediated cytoplasmic splicing that is required for its activation. These data indicate that OsbZIP39 may be directly involved in the regulation of several ER stress response genes. PMID- 22084316 TI - Renal transplantation. PMID- 22084315 TI - Extensive genomic variation within clonal complexes of Neisseria meningitidis. AB - Meningococcal disease is a widely distributed complex disease affecting all age categories. It can cause severe meningitis and septicemia, especially in unvaccinated infants and young children. The causative agent, Neisseria meningitidis (Nm), can be phenotypically and genetically differentiated into serogroups and sequence types (STs) and has a highly dynamic population structure. To obtain a deeper understanding of the epidemiology of Nm, we sequenced seven Nm genomes. Large-scale genomic analysis was conducted with these 7 Nm genomes, 27 additional Nm genomes from GenBank, and 4 other Neisseria genomes. We observed extensive homologous recombination in all gene functional categories among different Nm genomes. Homologous recombination is so frequent that it has resulted in numerous chimeric open reading frames, including genes in the capsule biosynthesis cluster and loci targeted by commercial vaccines. Our results reveal that, despite widespread use, evolutionary relationships inferred from the standard seven-gene multilocus sequence typing (MLST) method could not predict virulence gene content or strain phenotype. In fact, up to 28% of the virulence-associated genes could differ between strains of identical STs. Consistent with previous studies, we found that allelic recombination is also associated with alterations in antibiotic susceptibility. Overall, these findings emphasize the extensive genomic plasticity of Nm and the limitations of standard molecular methods to quantify this genotypic and phenotypic diversity. PMID- 22084317 TI - Be more radical, vocal, and bold to improve patient safety, conference hears. PMID- 22084318 TI - Nature defends itself in High Court over issue of "freedom of scientific expression". PMID- 22084319 TI - Medical researchers in Germany receive largest grants of all university disciplines. PMID- 22084320 TI - Definition of refugee is inadequate for current patterns of migration in armed conflicts, report says. PMID- 22084321 TI - EU is set to use innovative solutions to help elderly people live more healthily. PMID- 22084322 TI - Government is not taking responsibility for improving air quality, MPs say. PMID- 22084323 TI - Attitudes toward newborn screening for cytomegalovirus infection. AB - OBJECTIVE: Newborns are not routinely screened for cytomegalovirus (CMV), the leading infectious cause of developmental disability. Congenital CMV satisfies a number of criteria for inclusion in newborn screening, and screening potentially offers benefits. Screening could also introduce harms such as anxiety and unnecessary costs for the families of the substantial proportion of CMV-infected children who never develop CMV-related disabilities. Our objective was to assess attitudes toward newborn screening for CMV. METHODS: We analyzed responses to 5 statements about CMV and newborn screening from 3922 participants in the 2009 HealthStyles survey, a national mail survey designed to include a group similar to the US population with respect to gender, age, race/ethnicity, income, and household size. Two-step cluster analysis was performed to identify clusters of parental attitudes. RESULTS: The majority of respondents strongly or somewhat agreed that they would want to have their newborn tested for CMV even if it was not performed routinely (84%), they had to pay $20 (87%), or CMV-related problems never developed (84%). Nearly half (47%) of them "would worry that the CMV test would lead to unneeded doctor visits and expenses," and 32% "think CMV problems are too rare to worry about." Three clusters of parent respondents were identified on the basis of their attitudes toward CMV screening: "strongly in favor" (31%), "moderately in favor" (49%), and "weakly opposed" (20%). CONCLUSIONS: Among most parents, costs, worry, and anxiety associated with newborn screening for CMV would be acceptable. Although attitudes were generally favorable, a minority of the parents were weakly opposed to newborn screening for CMV. PMID- 22084324 TI - Contemporary ethical issues in human milk-banking in the United States. AB - Donor human milk has been used in the United States for >90 years, but recent advances in human milk science and laboratory techniques have led to increasing use of this resource. Pediatricians began using donor human milk in the 1900s in response to anecdotal observation that premature infants had better health outcomes when receiving their own mothers' milk. Since then, a formalized human milk-banking system developed in the mid-1980s and distributed >1 million ounces of pasteurized donor human milk in 2008. Despite growth in the use of pasteurized donor human milk, there is little discussion in the medical literature regarding the ethical considerations of collection and use of this resource. Key ethical considerations include issues surrounding medical decision-making and informed consent, increasing the limited supply of human milk, how ethically to allocate this scarce resource, and concerns linked to the marketing of a human milk. PMID- 22084325 TI - Medical-legal partnership: impact on patients with sickle cell disease. AB - OBJECTIVE: To determine the types of legal problems addressed by the Health Law Partnership (HeLP) and the impact of the legal interventions in pediatric patients with sickle cell disease (SCD) or its variants. We hypothesized that an interdisciplinary team that includes lawyers would positively affect the social determinants of health that affect patients with SCD. METHODS: The HeLP database was retrospectively queried for all patients with the diagnosis of SCD or 1 of its variants who had been seen by the lawyers of HeLP between April 2004 and September 2010. Data collected in this cohort of patients included income level of the patient/client, the initial presenting problems, any patient/parent/guardian problems identified during the legal checkup, and the type of legal assistance provided. Estimated annualized financial outcomes were calculated. RESULTS: From April 2004 through September 2010, 71 parents/guardians with 76 children with SCD were referred to the HeLP for legal intervention. Of the 71 parents/guardians, 33 were at <100% of the federal poverty level. There were 106 initial case problems identified in the 71 parents/guardians; 51 of 106 problems were directly related to the child. An additional 93 issues were identified during the legal checkup. Of 106 cases, 99 were closed with 21 resulting in a measurable gain of benefits. CONCLUSIONS: In a cohort of families of children with SCD, incorporating access to legal services as part of the care plan resulted in a positive impact on these patients/parents/guardians. The impact was directly attributable to the intervention of the HeLP. PMID- 22084326 TI - Adolescent vaccination-coverage levels in the United States: 2006-2009. AB - BACKGROUND: From 2005 through 2007, 3 vaccines were added to the adolescent vaccination schedule: tetanus-diphtheria-acellular pertussis (TdaP); meningococcal conjugate (MenACWY); and human papillomavirus (HPV) for girls. OBJECTIVE: To assess implementation of new adolescent vaccination recommendations. METHODS: Data from the 2006-2009 National Immunization Survey Teen, an annual provider-verified random-digit-dial survey of vaccination coverage in US adolescents aged 13 to 17 years, were analyzed. Main outcome measures included percentage of adolescents who received each vaccine according to survey year; potential coverage if all vaccines were administered during the same vaccination visit; and, among unvaccinated adolescents, the reasons for not receiving vaccine. RESULTS: Between 2006 and 2009, >=1 TdaP and >=1 MenACWY coverage increased from 11% to 56% and 12% to 54%, respectively. Between 2007 and 2009, >=1 HPV coverage among girls increased from 25% to 44%; between 2008 and 2009, >=3 HPV coverage increased from 18% to 27%. In 2009, vaccination coverage could have been >80% for Td/TdaP and MenACWY and as high as 74% for the first HPV dose if providers had administered all recommended vaccines during the same vaccination visit. For all years, the top reported reasons for not vaccinating were no knowledge about the vaccine, provider did not recommend, and vaccine is not needed/necessary (for TdaP and MenACWY) and adolescent is not sexually active, no knowledge about the vaccine, and vaccine is not needed/necessary (for HPV). CONCLUSIONS: Adolescent vaccination coverage is increasing but could be improved. Strategies are needed to increase parental knowledge about adolescent vaccines and improve provider recommendation and administration of all vaccines during the same visit. PMID- 22084327 TI - Delayed acyclovir and outcomes of children hospitalized with eczema herpeticum. AB - OBJECTIVE: To describe the epidemiology and outcomes of children hospitalized with eczema herpeticum and to determine the association with delayed acyclovir on outcomes. PATIENTS AND METHODS: This was a multicenter retrospective cohort study conducted between January 1, 2001, and March 31, 2010, of 1331 children aged 2 months to 17 years with eczema herpeticum from 42 tertiary care children's hospitals in the Pediatric Health Information System database. Multivariable linear regression models determined the association between delayed acyclovir therapy and the main outcome measure: hospital length of stay (LOS). RESULTS: There were no deaths during the study period. Staphylococcus aureus infection was diagnosed in 30.3% of the patients; 3.9% of the patients had a bloodstream infection. Fifty-one patients (3.8%) required ICU admission. There were 893 patients (67.1%) who received acyclovir on the first day of admission. The median LOS increased with each day delay in acyclovir initiation. In multivariable analysis, delay of acyclovir initiation by 1 day was associated with an 11% increased LOS (95% confidence interval [CI]: 3%-20%; P = .008), and LOS increased by 41% when acyclovir was started on day 3 (95% CI: 19%-67%; P < .001) and by 98% when started on day 4 to 7 (95% CI: 60%-145%; P < .001). Use of topical corticosteroids on day 1 of hospitalization was not associated with LOS. CONCLUSIONS: Delay of acyclovir initiation is associated with increased LOS in hospitalized children with eczema herpeticum. Use of topical corticosteroids on admission is not associated with increased LOS. The mortality rate of hospitalized children with eczema herpeticum is low. PMID- 22084328 TI - Leveraging state immunization information systems to measure the effectiveness of rotavirus vaccine. AB - OBJECTIVE: Electronic immunization information systems (IISs) are now established in almost all US states. We used the IIS in Minnesota, Georgia, and Connecticut for immunization data and as the source of 1 of 2 control groups to measure pentavalent rotavirus vaccine (RV5) effectiveness (VE) using case-control methodology. PATIENTS AND METHODS: Case-subjects were vaccine-eligible children who presented to 1 of 5 hospitals or emergency departments with gastroenteritis and had rotavirus antigen detected in stool during any of 3 rotavirus seasons (2007-2009). Two control groups were used: children with gastroenteritis who tested negative for rotavirus and children from the IIS matched by zip code and birth date. In Minnesota and Georgia, immunization records for rotavirus-positive and -negative children were also obtained from providers. RESULTS: Overall, 402 (96%) rotavirus case-subjects and 825 (97%) rotavirus-negative controls who met eligibility criteria were found in the IISs. Ten IIS controls were identified for each case. VE estimates for RV5 were similar across control groups, immunization data sources, and states. VE point estimates for 3 vs 0 doses were 89% to 94% among children aged 8 months or older and 86% to 92% among those aged 24 months or older. VE for 2 doses was >=90% among children aged 8 months or older, and VE for 1 dose was 66% among those aged 6 weeks through 5 months. CONCLUSIONS: Three RV5 doses confer sustained protection against rotavirus disease during the first 3 years of life in US children. Two RV5 doses also seem to provide good protection. IISs can be valuable tools for assessing the effectiveness of vaccines administered to young children. PMID- 22084329 TI - Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. PMID- 22084330 TI - Preoperative anxiety and pain sensitivity are independent predictors of propofol and sevoflurane requirements in general anaesthesia. AB - BACKGROUND: Psychological factors are thought to drive inter-patient variations in anaesthetic and analgesic requirements. This cross-sectional study investigated whether preoperative psychological factors can predict anaesthetic requirements and postoperative pain. METHODS: Before total thyroidectomy, 100 consecutive women completed the Spielberger's State-Trait Anxiety Inventory (STAI) and the pain sensitivity questionnaire (PSQ). Target-controlled propofol was administered for induction of anaesthesia, and sevoflurane-oxygen-air was given to maintain equal depths of anaesthesia, as determined by bispectral index (BIS) monitoring. RESULTS: Patients with higher anxiety scores (state and trait) required greater amounts of propofol to reach light (BIS=85) and moderate (BIS=75) levels of sedation, but only trait anxiety was significantly associated with propofol requirements in reaching a deep level of sedation (BIS=65). The MAC hour of sevoflurane was significantly correlated only with PSQ scores. The postoperative pain intensity was significantly correlated with both STAI and PSQ. CONCLUSIONS: Preoperative anxiety and pain sensitivity are independent predictors of propofol and sevoflurane requirements in general anaesthesia. Anaesthetic and analgesic doses could be modified based on the patient's preoperative anxiety and pain sensitivity. PMID- 22084331 TI - Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. AB - BACKGROUND: Guidelines recommend that patients receiving warfarin undergo international normalized ratio (INR) monitoring every 4 weeks. OBJECTIVE: To investigate whether assessment of warfarin dosing every 12 weeks is as safe as assessment every 4 weeks. DESIGN: Noninferiority randomized trial. The randomization schedule (in a 1:1 ratio) was computer-generated, and allocation was concealed until the database was locked by using a centralized schedule. Patients, study and clinical personnel, adjudicators of clinical events, and the study statistician were blinded to treatment assignment. (ClinicalTrials.gov registration number: NCT00356759) SETTING: Single center in Hamilton, Ontario, Canada. PATIENTS: 250 patients receiving long-term warfarin therapy, whose dose was unchanged for at least 6 months; 226 completed the study. INTERVENTION: Dosing assessment every 12 weeks (n = 124) compared with every 4 weeks (n = 126) for 12 months. Patients in the 12-week group were tested every 4 weeks; sham INRs within the target range were reported for two of the three 4-week periods. MEASUREMENTS: Percentage of time in the therapeutic range (primary outcome) and number of extreme INRs, changes in maintenance dose, major bleeding events, objectively verified thromboembolism, and death (secondary outcomes). RESULTS: The percentage of time in the therapeutic range was 74.1% (SD, 18.8%) in the 4 week group compared with 71.6% (SD, 20.0%) in the 12-week group (absolute difference, 2.5 percentage points [1-sided 97.5% upper confidence bound, 7.3 percentage points]; noninferiority P = 0.020 for a 7.5-percentage point margin). Fewer patients in the 12-week group than in the 4-week group had any dose changes (37.1% vs. 55.6%; absolute difference, 18.5 percentage points [95% CI, 6.1 to 30.0 percentage points]; P = 0.004). Secondary outcomes did not differ between groups. LIMITATIONS: Patients in the 12-week group had testing and contact with clinic staff every 4 weeks. The study was conducted at a single center and used surrogate outcomes. CONCLUSION: Assessment of warfarin dosing every 12 weeks seems to be safe and noninferior to assessment every 4 weeks. A comparison of INR testing, patient contact, and warfarin dose assessment every 12 weeks versus every 4 weeks is necessary before INR testing every 12 weeks can be routinely recommended for practice. PRIMARY FUNDING SOURCE: Physicians' Services Incorporated Foundation. PMID- 22084332 TI - Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. AB - BACKGROUND: CHADS(2) is a simple, validated risk score for predicting the risk for stroke in patients with atrial fibrillation not treated with anticoagulants. There are sparse data on the risk for thrombotic and bleeding complications according to the CHADS(2) score in patients receiving anticoagulant therapy. OBJECTIVE: To evaluate the prognostic importance of CHADS(2) risk score in patients with atrial fibrillation receiving oral anticoagulants, including the vitamin K antagonist warfarin and the direct thrombin inhibitor dabigatran. DESIGN: Subgroup analysis of a randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00262600) SETTING: Multinational study setting. PATIENTS: 18 112 patients with atrial fibrillation who were receiving oral anticoagulants. MEASUREMENTS: Baseline CHADS(2) score, which assigns 1 point each for congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and 2 points for stroke. RESULTS: Distribution of CHADS(2) scores were as follows: 0 to 1-5775 patients; 2-6455 patients; and 3 to 6-5882 patients. Annual rates of the primary outcome of stroke or systemic embolism among all participants were 0.93% in patients with a CHADS(2) score of 0 to 1, 1.22% in those with a score of 2, and 2.24% in those with a score of 3 to 6. Annual rates of other outcomes among all participants with CHADS(2) scores of 0 to 1, 2, and 3 to 6, respectively, were the following: major bleeding, 2.26%, 3.11%, and 4.42%; intracranial bleeding, 0.31%, 0.40%, and 0.61%; and vascular mortality, 1.35%, 2.39%, and 3.68% (P < 0.001 for all comparisons). Rates of stroke or systemic embolism, major and intracranial bleeding, and vascular and total mortality each increased in the warfarin and dabigatran groups as CHADS(2) score increased. The rates of stroke or systemic embolism with dabigatran, 150 mg twice daily, and of intracranial bleeding with dabigatran, 150 mg or 110 mg twice daily, were lower than those with warfarin; there was no significant heterogeneity in subgroups defined by CHADS(2) scores. LIMITATION: These analyses were not prespecified and should be deemed exploratory. CONCLUSION: Higher CHADS(2) scores were associated with increased risks for stroke or systemic embolism, bleeding, and death in patients with atrial fibrillation receiving oral anticoagulants. PRIMARY FUNDING SOURCE: Boehringer Ingelheim. PMID- 22084334 TI - Whole-body vibration therapy for osteoporosis: state of the science. AB - Clinical guidelines for osteoporosis recommend dietary and pharmacologic interventions and weight-bearing exercise to prevent bone fractures. These interventions sometimes have low adherence and can cause adverse effects. A proposed alternative or adjunctive treatment is whole-body vibration therapy (WBV), in which energy produced by a forced oscillation is transferred to an individual from a mechanical vibration platform. Whole-body vibration platforms are not approved by the U.S. Food and Drug Administration for medical purposes. This review provides a broad overview of important issues related to WBV therapy for prevention and treatment of osteoporosis. Relying on key informants and a search of the gray and published literature from January 2000 to August 2011, the investigators found that the designs of WBV platforms and protocols for their use vary widely. The optimal target population for the therapy is not defined. Although WBV has some theoretical advantages, key informants have voiced several concerns, including uncertain safety and potential consumer confusion between low intensity vibration platforms intended for osteoporosis therapy and high intensity platforms intended for exercise. Finally, the scant literature did not establish whether WBV therapy leads to clinically important increases in bone mineral density or reduces risk for fracture. PMID- 22084333 TI - Effect of 12 months of whole-body vibration therapy on bone density and structure in postmenopausal women: a randomized trial. AB - BACKGROUND: Although data from studies in animals demonstrated beneficial effects of whole-body vibration (WBV) therapy on bone, clinical trials in postmenopausal women showed conflicting results. OBJECTIVE: To determine whether WBV improves bone density and structure. DESIGN: A 12-month, single-center, superiority, randomized, controlled trial with 3 parallel groups. (ClinicalTrials.gov registration number: NCT00420940) SETTING: Toronto General Hospital, Ontario, Canada. PARTICIPANTS: 202 healthy postmenopausal women with bone mineral density (BMD) T-scores between -1.0 and -2.5 who were not receiving prescription bone medications. INTERVENTION: Participants were randomly assigned to 1 of 3 groups (1:1:1 ratio) by using a block-randomization scheme and sealed envelopes. They were asked to stand on a low-magnitude (0.3g) 90-Hz or 30-Hz WBV platform for 20 minutes daily or to serve as control participants; all participants received calcium and vitamin D. MEASUREMENTS: Bone outcome assessors, who were blinded to group assignment, determined trabecular volumetric BMD and other measurements of the distal tibia and distal radius with high-resolution peripheral quantitative computed tomography and areal BMD with dual-energy x-ray absorptiometry at baseline and at 12 months. RESULTS: 12 months of WBV therapy had no significant effect on any bone outcomes compared with no WBV therapy. For the primary outcome of tibial trabecular volumetric BMD, mean change from baseline was 0.4 mg/cm(3) (95% CI, -0.4 to 1.2 mg/cm(3)) in the 90-Hz WBV group, -0.1 mg/cm(3) (CI, -1.0 to 0.8 mg/cm(3)) in the 30-Hz WBV group, and -0.2 mg/cm(3) (CI, -1.1 to 0.6 mg/cm(3)) in the control group (P = 0.55). Changes in areal BMD at the femoral neck, total hip, and lumbar spine were also similar among the groups. Overall, low-magnitude WBV at both 90 and 30 Hz was well-tolerated. LIMITATIONS: Adherence to WBV ranged from 65% to 79%. Double-blinding was not possible. CONCLUSION: Whole-body vibration therapy at 0.3g and 90 or 30 Hz for 12 months did not alter BMD or bone structure in postmenopausal women who received calcium and vitamin D supplementation. PMID- 22084335 TI - Promises and challenges of stem cell research for regenerative medicine. AB - In recent years, stem cells have generated increasing excitement, with frequent claims that they are revolutionizing medicine. For those not directly involved in stem cell research, however, it can be difficult to separate fact from fiction or realistic expectation from wishful thinking. This article aims to provide internists with a clear and concise introduction to the field. While recounting some scientific and medical milestones, the authors discuss the 3 main varieties of stem cells-adult, embryonic, and induced pluripotent-comparing their advantages and disadvantages for clinical medicine. The authors have sought to avoid the moral and political debates surrounding stem cell research, focusing instead on scientific and medical issues. PMID- 22084336 TI - Learning the respective roles of warfarin and dabigatran to prevent stroke in patients with nonvalvular atrial fibrillation. PMID- 22084337 TI - A matter of the heart. PMID- 22084338 TI - House call. PMID- 22084339 TI - Hospital care and medical utilization after discharge. PMID- 22084340 TI - Hospital care and medical utilization after discharge. PMID- 22084341 TI - Hospital care and medical utilization after discharge. PMID- 22084342 TI - Hospital care and medical utilization after discharge. PMID- 22084343 TI - Hospital care and medical utilization after discharge. PMID- 22084344 TI - Hospital care and medical utilization after discharge. PMID- 22084345 TI - Hospital care and medical utilization after discharge. PMID- 22084346 TI - Therapy-related acute myelogenous leukemia in a hydroxyurea-treated patient with sickle cell anemia. PMID- 22084347 TI - Summaries for patients: can people who are receiving steady doses of warfarin have their dose assessed less frequently? PMID- 22084348 TI - Summaries for patients: whole-body vibration therapy for the prevention of bone loss. PMID- 22084349 TI - ACP Journal Club. Simvastatin plus ezetimibe reduced major atherosclerotic events in patients with chronic kidney disease. PMID- 22084350 TI - ACP Journal Club. Review: lowering systolic BP to <= 135 mm Hg reduces CV events in type 2 diabetes/IFG/IGT. PMID- 22084351 TI - ACP Journal Club. Review: cholecalciferol (vitamin D3) reduces mortality in adults; other forms of vitamin D do not. PMID- 22084352 TI - ACP Journal Club. Influenza vaccination reduced cardiovascular events in patients hospitalized with an acute coronary syndrome. PMID- 22084353 TI - ACP Journal Club. Screening with low-dose computed tomography reduced lung cancer mortality in high-risk patients. PMID- 22084354 TI - ACP Journal Club. Adding short-term androgen-deprivation therapy to radiotherapy improved survival in localized prostate cancer. PMID- 22084355 TI - ACP Journal Club. Review: pregabalin and other drugs reduce pain in patients with painful diabetic neuropathy. PMID- 22084356 TI - ACP Journal Club. Systematic pain management reduced agitation in nursing home residents with dementia. PMID- 22084357 TI - ACP Journal Club. Review: cholinesterase inhibitors but not memantine increase syncope in older adults with mild cognitive impairment or dementia. PMID- 22084358 TI - ACP Journal Club. Late initiation of parenteral nutrition reduced length of intensive care unit stay. PMID- 22084359 TI - ACP Journal Club. Review: several instruments are accurate for evaluating patient capacity for medical treatment decision-making. PMID- 22084360 TI - ACP Journal Club. A 5-item score predicted risk for warfarin-associated major hemorrhage in patients with atrial fibrillation. PMID- 22084362 TI - Novel staging system for predicting disease-specific survival in patients with breast cancer treated with surgery as the first intervention: time to modify the current American Joint Committee on Cancer staging system. AB - PURPOSE: American Joint Committee on Cancer (AJCC) staging is used to determine breast cancer prognosis, yet patient survival within each stage shows wide variation. We hypothesized that differences in biology influence this variation and that addition of biologic markers to AJCC staging improves determination of prognosis. PATIENTS AND METHODS: We identified a cohort of 3,728 patients who underwent surgery as the first intervention between 1997 and 2006. A Cox proportional hazards model, with backward stepwise exclusion of factors and stratification on pathologic stage (PS), was used to test the significance of adding grade (G), lymphovascular invasion (L), estrogen receptor (ER) status (E), progesterone receptor (PR) status, combined ER and PR status (EP), or combined ER, PR, and human epidermal growth factor receptor 2 status (M). We assigned values of 0 to 2 to these disease-specific survival (DSS) -associated factors and assessed six different staging systems: PS, PS + G, PS + G L, PS + G E, PS + G EP, and PS + G M. We compared 5-year DSS rates, Akaike's information criterion (AIC), and Harrell's concordance index (C-index) between systems. Surveillance, Epidemiology, and End Results data were used as the external validation cohort (n = 26,711). RESULTS: Median follow-up was 6.5 years, and 5-year DSS rate was 97.4%. The PS + G E status staging system was most precise, with a low AIC (1,931.9) and the highest C-index (0.80). PS + G E status was confirmed to stratify outcomes in internal bootstrapping samples and the external validation cohort. CONCLUSION: Our results validate an improved breast cancer staging system that incorporates grade and ER status. We recommend that biologic markers be incorporated into revised versions of the AJCC staging system. PMID- 22084361 TI - Aspirin in the chemoprevention of colorectal neoplasia: an overview. AB - Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term posttrial follow-up of nearly 14,000 patients from four randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about five years was associated with a 34% reduction in 20-year CRC mortality. A separate metaanalysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in four randomized adenoma prevention trials showed that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least two years, there was a 50% or more reduction in the risk of CRC commencing five years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin's anticancer effect require further investigation. PMID- 22084363 TI - Acute isolated transmural neutropenic gastritis. PMID- 22084364 TI - Multiple cytokine-producing solitary plasmacytoma of bone with expression of cytokine receptors. PMID- 22084365 TI - Activity of alemtuzumab in acute myelogenous leukemia and myelodysplastic syndrome with chromosome 7 aberrations. PMID- 22084366 TI - Predicting survival after curative colectomy for cancer: individualizing colon cancer staging. AB - PURPOSE: Cancer staging determines extent of disease, facilitating prognostication and treatment decision making. The American Joint Committee on Cancer (AJCC) TNM classification system is the most commonly used staging algorithm for colon cancer, categorizing patients on the basis of only these three variables (tumor, node, and metastasis). The purpose of this study was to extend the seventh edition of the AJCC staging system for colon cancer to incorporate additional information available from tumor registries, thereby improving prognostic accuracy. METHODS: Records from 128,853 patients with primary colon cancer reported to the Surveillance, Epidemiology and End Results Program from 1994 to 2005 were used to construct and validate three survival models for patients with primary curative-intent surgery. Independent training/test data sets were used to develop and test alternative models. The seventh edition TNM staging system was compared with models supplementing TNM staging with additional demographic and tumor variables available from the registry by calculating a concordance index, performing calibration, and identifying the area under receiver operating characteristic (ROC) curves. RESULTS: Inclusion of additional registry covariates improved prognostic estimates. The concordance index rose from 0.60 (95% CI, 0.59 to 0.61) for the AJCC model, with T- and N-stage variables, to 0.68 (95% CI, 0.67 to 0.68) for the model including tumor grade, number of collected metastatic lymph nodes, age, and sex. ROC curves for the extended model had higher sensitivity, at all values of specificity, than the TNM system; calibration curves indicated no deviation from the reference line. CONCLUSION: Prognostic models incorporating readily available data elements outperform the current AJCC system. These models can assist in personalizing treatment and follow-up for patients with colon cancer. PMID- 22084368 TI - The care people need and the education of physicians. PMID- 22084369 TI - Prognostic impact of morphologic and phenotypic features of childhood ALK positive anaplastic large-cell lymphoma: results of the ALCL99 study. AB - PURPOSE: The prognostic value of pathologic characteristics of childhood ALK positive anaplastic large-cell lymphomas (ALCL), such as histologic subtypes, immunophenotype, and presence of the t(2;5) translocation or its variants, was assessed. PATIENTS AND METHODS: All 375 patients with systemic ALK-positive ALCL included in an international trial launched by the European Intergroup for Childhood Non-Hodgkin's Lymphoma were reviewed by an international panel of pathologists based on conventional hematoxylin and eosin-stained and immunostained sections and classified according to the 2001 WHO classification. RESULTS: A small-cell (SC) or lymphohistiocytic (LH) component was observed in 114 (32%) of 361 patients, whereas ALCL of common type was diagnosed in 235 (65%) of 361 patients. Regarding the histologic subtyping of patients within the two categories of ALCL (with v without SC/LH component), the concordance between the national and international reviews was quite good, with a kappa index equal to 0.67 (95% CI, 0.57 to 0.75). The presence of an SC/LH component was significantly associated with a high risk of failure (hazard ratio [HR], 2.0; 95% CI, 1.3 to 3.0; P = .002) in the multivariate analysis controlling for clinical characteristics, as well as the perivascular pattern (HR, 1.7; 95% CI, 1.1 to 2.7; P = .01), whereas CD3 positivity was significantly associated with a high risk of failure only in univariate analysis. CONCLUSION: Our study, which to our knowledge includes the largest series of childhood systemic ALK-positive ALCL so far, demonstrates the adverse prognostic value of SC and/or LH morphologic features. Combining these histologic characteristics with other biologic or clinical factors might have a high potential for future risk stratification and treatment. PMID- 22084370 TI - Taxane doublets for metastatic breast cancer: do we need another cytotoxic pair or another approach? PMID- 22084371 TI - Survival data from a phase II, open-label study of pazopanib or lapatinib monotherapy in patients with advanced and recurrent cervical cancer. PMID- 22084372 TI - Medical oncologists' attitudes and practice in cancer pain management: a national survey. AB - PURPOSE: To evaluate the attitudes, knowledge, and practices of US medical oncologists that are related to management of cancer pain. METHODS: An anonymous survey was mailed to a geographically representative sample of medical oncologists randomly selected from the American Medical Association's Physician Master File. RESULTS: From a total of 2,000 oncologists, 354 responded to the original questionnaire and 256 responded to one of two subsequent shortened versions (overall response rate, 32%). Responders were demographically similar to all US medical oncologists. Using numeric rating scales of 0 to 10, oncologists rated their specialty highly for the ability to manage cancer pain (median, 7; interquartile range [IQR], 6 to 8) but rated their peers as more conservative prescribers than themselves (median, 3; IQR, 2 to 5). The quality of pain management training during medical school and residency was rated as 3 (IQR, 1 to 5) and 5 (IQR, 3 to 7), respectively. The most important barriers to pain management were poor assessment (median, 6; IQR, 4 to 7) and patient reluctance to take opioids (median, 6; IQR, 5 to 7) or report pain (median, 6; IQR, 4 to 7). Other barriers included physician reluctance to prescribe opioids (median, 5; IQR, 3 to 7) and perceived excessive regulation (median, 4; IQR, 2 to 7). In response to two vignettes describing challenging clinical scenarios, 60% and 87%, respectively, endorsed treatment decisions that would be considered unacceptable by pain specialists. Frequent referrals to pain or palliative care specialists were reported by only 14% and 16%, respectively. CONCLUSION: These data suggest that, for more than 20 years, a focus on cancer pain has not adequately addressed the perception of treatment barriers or limitations in pain-related knowledge and practice within the oncology community. Additional efforts are needed to achieve meaningful progress. PMID- 22084373 TI - Adverse prognostic impact of abnormal lesions detected by genome-wide single nucleotide polymorphism array-based karyotyping analysis in acute myeloid leukemia with normal karyotype. AB - PURPOSE: This study attempted to analyze the prognostic role of single nucleotide polymorphism array (SNP-A) -based karyotying in 133 patients with acute myeloid leukemia with normal karyotype (AML-NK), which presents with diverse clinical outcomes, thus requiring further stratification of patient subgroups according to their prognoses. PATIENTS AND METHODS: A total of 133 patients with AML-NK confirmed by metaphase cytogenetics (MC) and fluorescent in situ hybridization analysis were included in this study. Analysis by Genome-Wide Human SNP 6.0 Array was performed by using DNAs derived from marrow samples at diagnosis. RESULTS: Forty-three patients (32.3%) had at least one abnormal SNP lesion that was not detected by MC. One hundred thirteen abnormal SNP lesions included 55 losses, 23 gains, and 35 copy-neutral losses of heterozygosity. Multivariate analyses showed that detection of abnormal SNP lesions by SNP-A karyotyping results in an unfavorable prognostic value for overall survival (hazard ratio [HR], 2.69; 95% CI, 1.50 to 4.82; P = .001); other significant prognostic factors included secondary AML (HR, 5.55; 95% CI, 1.80 to 17.14; P = .003), presence of the FLT3 mutation (HR, 3.17; 95% CI, 1.71 to 5.87; P < .001), and age (HR, 1.03; 95% CI, 1.01 to 1.05; P = .020). CONCLUSION: Our data demonstrated that abnormal SNP lesions detected by SNP-A karyotyping might indicate an adverse prognosis in patients with AML-NK, thus requiring a more sophisticated treatment strategy for improvement of treatment outcomes. PMID- 22084374 TI - Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group. AB - PURPOSE: The objective of this phase III study was to compare the efficacy of gemcitabine plus docetaxel (GD) versus docetaxel in patients with advanced breast cancer. PATIENTS AND METHODS: Predominantly human epidermal growth factor receptor 2 (HER2) -negative patients were randomly assigned to gemcitabine (1,000 mg/m(2)) on days 1 and 8 plus docetaxel (75 mg/m(2)) on day 8 or to docetaxel (100 mg/m(2)) on day 1, every 21 days. Patients were untreated or had prior (neo)adjuvant chemotherapy or a single anthracycline-based chemotherapy regimen for metastatic breast cancer. The primary end point was time to progression (TTP), and secondary end points were overall survival (OS), response rate (RR), and toxicity. RESULTS: A total of 170 patients were allocated to GD, and 167 were allocated to docetaxel. Median TTP on GD was 10.3 months versus 8.3 months on docetaxel (hazard ratio [HR], 0.77; 95% CI, 0.59 to 1.01; log-rank P = .06). The adjusted Cox proportional model for TTP showed a significant difference favoring the combination (HR, 0.68; 95% CI, 0.51 to 0.90; P = .007). However, RR was similar (GD, 36%; docetaxel, 34%), and OS was not different (P = .57). Grades 3 to 4 neutropenia was common (GD, 75%; docetaxel, 69%); infection was reported in 26% and 21% of patients in the GD and docetaxel groups, respectively. Grades 3 to 4 thrombocytopenia was more frequent with GD (GD, 16%; docetaxel, 0.6%), and peripheral neuropathy was higher with docetaxel (GD, 5%; docetaxel, 16%). CONCLUSION: GD compared with docetaxel demonstrated increased TTP in metastatic breast cancer. However, RR and OS were similar. Thus, the addition of gemcitabine failed to demonstrate any clinically meaningful benefit when combined with docetaxel. PMID- 22084375 TI - The cell cycle. Preface. PMID- 22084376 TI - The cell cycle. PMID- 22084377 TI - Quiescence: early evolutionary origins and universality do not imply uniformity. AB - Cell cycle investigations have focused on relentless exponential proliferation of cells, an unsustainable situation in nature. Proliferation of cells, whether microbial or metazoan, is interrupted by periods of quiescence. The vast majority of cells in an adult metazoan lie quiescent. As disruptions in this quiescence are at the foundation of cancer, it will be important for the field to turn its attention to the mechanisms regulating quiescence. While often presented as a single topic, there are multiple forms of quiescence each with complex inputs, some of which are tied to conceptually challenging aspects of metazoan regulation such as size control. In an effort to expose the enormity of the challenge, I describe the differing biological purposes of quiescence, and the coupling of quiescence in metazoans to growth and to the structuring of tissues during development. I emphasize studies in the organism rather than in tissue culture, because these expose the diversity of regulation. While quiescence is likely to be a primitive biological process, it appears that in adapting quiescence to its many distinct biological settings, evolution has diversified it. Consideration of quiescence in different models gives us an overview of this diversity. PMID- 22084378 TI - Nutrient limitations alter cell division control and chromosome segregation through growth-related kinases and phosphatases. AB - In dividing fission yeast Schizosaccharomyces pombe cells, the balance between Wee1 kinase and Cdc25 phosphatase which control the cyclin-dependent kinase (CDK) at the G2-M transition determines the rod-shaped cell length. Under nitrogen source starvation or glucose limitation, however, cell size determination is considerably modulated, and cell size shortening occurs for wild-type cells. For several mutants of kinases or phosphatases, including CDK, target of rapamycin complex (TORC) 1 and 2, stress-responsive mitogen-activated protein kinase (MAPK) Sty1/Spc1, MAPK kinase Wis1, calcium- and calmodulin-dependent protein kinase kinase-like Ssp1, and type 2A and 2A-related phosphatases inhibitor Sds23, this cell shortening does not normally occur. In tor1 and ssp1 mutants, cell elongation is observed. Sds23 that binds to and inhibits 2A and 2A-related phosphatases is synergistic with Ssp1 in the cell size determination and survival under low glucose and nitrogen source. Tor2 (TORC1) is required for growth, whereas Tor1 (TORC2) is needed for determining division size according to different nutrient conditions. Surprisingly, in growth-diminished tor2 mutant or rapamycin-treated cells, the requirement of separase/Cut1-securin/Cut2 essential for chromosome segregation is greatly alleviated. By contrast, defects of tor1 with secruin/cut2 or overproduction of Cut1 are additive. While Tor1 and Tor2 are opposite in their apparent functions, both may actually coordinate cell division with growth in response to the changes in nutrients. PMID- 22084379 TI - Regulation of entry into gametogenesis. AB - Gametogenesis is a fundamental aspect of sexual reproduction in eukaryotes. In the unicellular fungi Saccharomyces cerevisiae (budding yeast) and Schizosaccharomyces pombe (fission yeast), where this developmental programme has been extensively studied, entry into gametogenesis requires the convergence of multiple signals on the promoter of a master regulator. Starvation signals and cellular mating-type information promote the transcription of cell fate inducers, which in turn initiate a transcriptional cascade that propels a unique type of cell division, meiosis, and gamete morphogenesis. Here, we will provide an overview of how entry into gametogenesis is initiated in budding and fission yeast and discuss potential conserved features in the germ cell development of higher eukaryotes. PMID- 22084380 TI - Evolution of networks and sequences in eukaryotic cell cycle control. AB - The molecular networks regulating the G1-S transition in budding yeast and mammals are strikingly similar in network structure. However, many of the individual proteins performing similar network roles appear to have unrelated amino acid sequences, suggesting either extremely rapid sequence evolution, or true polyphyly of proteins carrying out identical network roles. A yeast/mammal comparison suggests that network topology, and its associated dynamic properties, rather than regulatory proteins themselves may be the most important elements conserved through evolution. However, recent deep phylogenetic studies show that fungal and animal lineages are relatively closely related in the opisthokont branch of eukaryotes. The presence in plants of cell cycle regulators such as Rb, E2F and cyclins A and D, that appear lost in yeast, suggests cell cycle control in the last common ancestor of the eukaryotes was implemented with this set of regulatory proteins. Forward genetics in non-opisthokonts, such as plants or their green algal relatives, will provide direct information on cell cycle control in these organisms, and may elucidate the potentially more complex cell cycle control network of the last common eukaryotic ancestor. PMID- 22084381 TI - Quality control in the initiation of eukaryotic DNA replication. AB - Origins of DNA replication must be regulated to ensure that the entire genome is replicated precisely once in each cell cycle. In human cells, this requires that tens of thousands of replication origins are activated exactly once per cell cycle. Failure to do so can lead to cell death or genome rearrangements such as those associated with cancer. Systems ensuring efficient initiation of replication, while also providing a robust block to re-initiation, play a crucial role in genome stability. In this review, I will discuss some of the strategies used by cells to ensure once per cell cycle replication and provide a quantitative framework to evaluate the relative importance and efficiency of individual pathways involved in this regulation. PMID- 22084382 TI - Surviving chromosome replication: the many roles of the S-phase checkpoint pathway. AB - Checkpoints were originally identified as signalling pathways that delay mitosis in response to DNA damage or defects in chromosome replication, allowing time for DNA repair to occur. The ATR (ataxia- and rad-related) and ATM (ataxia-mutated) protein kinases are recruited to defective replication forks or to sites of DNA damage, and are thought to initiate the DNA damage response in all eukaryotes. In addition to delaying cell cycle progression, however, the S-phase checkpoint pathway also controls chromosome replication and DNA repair pathways in a highly complex fashion, in order to preserve genome integrity. Much of our understanding of this regulation has come from studies of yeasts, in which the best characterized targets are the stimulation of ribonucleotide reductase activity by multiple mechanisms, and the inhibition of new initiation events at later origins of DNA replication. In addition, however, the S-phase checkpoint also plays a more enigmatic and apparently critical role in preserving the functional integrity of defective replication forks, by mechanisms that are still understood poorly. This review considers some of the key experiments that have led to our current understanding of this highly complex pathway. PMID- 22084383 TI - Regulatory networks integrating cell cycle control with DNA damage checkpoints and double-strand break repair. AB - Double-strand breaks (DSBs), arising from exposure to exogenous clastogens or as a by-product of endogenous cellular metabolism, pose grave threats to genome integrity. DSBs can sever whole chromosomes, leading to chromosomal instability, a hallmark of cancer. Healing broken DNA takes time, and it is therefore essential to temporarily halt cell division while DSB repair is underway. The seminal discovery of cyclin-dependent kinases as master regulators of the cell cycle unleashed a series of studies aimed at defining how the DNA damage response network delays cell division. These efforts culminated with the identification of Cdc25, the protein phosphatase that activates Cdc2/Cdk1, as a critical target of the checkpoint kinase Chk1. However, regulation works both ways, as recent studies have revealed that Cdc2 activity and cell cycle position determine whether DSBs are repaired by non-homologous end-joining or homologous recombination (HR). Central to this regulation are the proteins that initiate the processing of DNA ends for HR repair, Mre11-Rad50-Nbs1 protein complex and Ctp1/Sae2/CtIP, and the checkpoint kinases Tel1/ATM and Rad3/ATR. Here, we review recent findings and provide insight on how proteins that regulate cell cycle progression affect DSB repair, and, conversely how proteins that repair DSBs affect cell cycle progression. PMID- 22084384 TI - A quantitative model for cyclin-dependent kinase control of the cell cycle: revisited. AB - The eukaryotic cell division cycle encompasses an ordered series of events. Chromosomal DNA is replicated during S phase of the cell cycle before being distributed to daughter cells in mitosis. Both S phase and mitosis in turn consist of an intricately ordered sequence of molecular events. How cell cycle ordering is achieved, to promote healthy cell proliferation and avert insults on genomic integrity, has been a theme of Paul Nurse's research. To explain a key aspect of cell cycle ordering, sequential S phase and mitosis, Stern & Nurse proposed 'A quantitative model for cdc2 control of S phase and mitosis in fission yeast'. In this model, S phase and mitosis are ordered by their dependence on increasing levels of cyclin-dependent kinase (Cdk) activity. Alternative mechanisms for ordering have been proposed that rely on checkpoint controls or on sequential waves of cyclins with distinct substrate specificities. Here, we review these ideas in the light of experimental evidence that has meanwhile accumulated. Quantitative Cdk control emerges as the basis for cell cycle ordering, fine-tuned by cyclin specificity and checkpoints. We propose a molecular explanation for quantitative Cdk control, based on thresholds imposed by Cdk-counteracting phosphatases, and discuss its implications. PMID- 22084385 TI - Switches and latches: a biochemical tug-of-war between the kinases and phosphatases that control mitosis. AB - Activation of the cyclin-dependent kinase (Cdk1) cyclin B (CycB) complex (Cdk1:CycB) in mitosis brings about a remarkable extent of protein phosphorylation. Cdk1:CycB activation is switch-like, controlled by two auto amplification loops--Cdk1:CycB activates its activating phosphatase, Cdc25, and inhibits its inhibiting kinase, Wee1. Recent experimental evidence suggests that parallel to Cdk1:CycB activation during mitosis, there is inhibition of its counteracting phosphatase activity. We argue that the downregulation of the phosphatase is not just a simple latch that suppresses futile cycles of phosphorylation/dephosphorylation during mitosis. Instead, we propose that phosphatase regulation creates coherent feed-forward loops and adds extra amplification loops to the Cdk1:CycB regulatory network, thus forming an integral part of the mitotic switch. These network motifs further strengthen the bistable characteristic of the mitotic switch, which is based on the antagonistic interaction of two groups of proteins: M-phase promoting factors (Cdk1:CycB, Cdc25, Greatwall and Endosulfine/Arpp19) and interphase promoting factors (Wee1, PP2A-B55 and a Greatwall counteracting phosphatase, probably PP1). The bistable character of the switch implies the existence of a CycB threshold for entry into mitosis. The end of G2 phase is determined by the point where CycB level crosses the CycB threshold for Cdk1 activation. PMID- 22084386 TI - Spindle assembly checkpoint: the third decade. AB - The spindle assembly checkpoint controls cell cycle progression during mitosis, synchronizing it with the attachment of chromosomes to spindle microtubules. After the discovery of the mitotic arrest deficient (MAD) and budding uninhibited by benzymidazole (BUB) genes as crucial checkpoint components in 1991, the second decade of checkpoint studies (2001-2010) witnessed crucial advances in the elucidation of the mechanism through which the checkpoint effector, the mitotic checkpoint complex, targets the anaphase-promoting complex (APC/C) to prevent progression into anaphase. Concomitantly, the discovery that the Ndc80 complex and other components of the microtubule-binding interface of kinetochores are essential for the checkpoint response finally asserted that kinetochores are crucial for the checkpoint response. Nevertheless, the relationship between kinetochores and checkpoint control remains poorly understood. Crucial advances in this area in the third decade of checkpoint studies (2011-2020) are likely to be brought about by the characterization of the mechanism of kinetochore recruitment, activation and inactivation of checkpoint proteins, which remains elusive for the majority of checkpoint components. Here, we take a molecular view on the main challenges hampering this task. PMID- 22084387 TI - Structural insights into anaphase-promoting complex function and mechanism. AB - The anaphase-promoting complex or cyclosome (APC/C) controls sister chromatid segregation and the exit from mitosis by catalysing the ubiquitylation of cyclins and other cell cycle regulatory proteins. This unusually large E3 RING-cullin ubiquitin ligase is assembled from 13 different proteins. Selection of APC/C targets is controlled through recognition of short destruction motifs, predominantly the D box and KEN box. APC/C-mediated coordination of cell cycle progression is achieved through the temporal regulation of APC/C activity and substrate specificity, exerted through a combination of co-activator subunits, reversible phosphorylation and inhibitory proteins and complexes. Recent structural and biochemical studies of the APC/C are beginning to reveal an understanding of the roles of individual APC/C subunits and co-activators and how they mutually interact to mediate APC/C functions. This review focuses on the findings showing how information on the structural organization of the APC/C provides insights into the role of co-activators and core APC/C subunits in mediating substrate recognition. Mechanisms of regulating and modulating substrate recognition are discussed in the context of controlling the binding of the co-activator to the APC/C, and the accessibility and conformation of the co activator when bound to the APC/C. PMID- 22084388 TI - The Renaissance or the cuckoo clock. AB - '...in Italy, for thirty years under the Borgias, they had warfare, terror, murder and bloodshed, but they produced Michelangelo, Leonardo da Vinci and the Renaissance. In Switzerland, they had brotherly love, they had five hundred years of democracy and peace-and what did that produce? The cuckoo clock'. Orson Welles as Harry Lime: The Third Man. Orson Welles might have been a little unfair on the Swiss, after all cuckoo clocks were developed in the Schwartzwald, but, more importantly, Swiss democracy gives remarkably stable government with considerable decision-making at the local level. The alternative is the battling city-states of Renaissance Italy: culturally rich but chaotic at a higher level of organization. As our understanding of the cell cycle improves, it appears that the cell is organized more along the lines of Switzerland than Renaissance Italy, and one major challenge is to determine how local decisions are made and coordinated to produce the robust cell cycle mechanisms that we observe in the cell as a whole. PMID- 22084389 TI - Whither systems biology. AB - Cell biologists are interested in how complexity arises from the interaction of different molecules. However, cells are many orders of magnitude larger than the protein-binding interfaces. To bridge these vast difference in scales, biologists construct hierarchies of organization of cellular structures. I describe how systems biology provides an approach to bridge these different scales. PMID- 22084391 TI - A population-based assessment of live births in women with systemic lupus erythematosus. AB - OBJECTIVES: The authors aim to calculate the number of live births, before and after systemic lupus erythematosus (SLE) diagnosis, in women diagnosed during their reproductive years and to compare this with general population rates. METHODS: The authors identified women with SLE using Quebec administrative databases (1 January 1994 to 31 December 2003). The authors determined the number of live births, and calculated the standardised incidence ratio (SIR) of observed to expected live births. RESULTS: 1334 women with SLE were identified. Overall, the number of live births over the interval (559) was below that which would be expected (708) (SIR 0.79; 95% CI 0.73 to 0.86). Compared with the general population, live births were substantially lower after SLE diagnosis (SIR 0.62; 95% CI 0.55 to 0.70) than before diagnosis (SIR 1.01; 95% CI 0.90 to 1.13). CONCLUSION: After diagnosis, women with SLE have substantially fewer live births than the general population. PMID- 22084390 TI - Translational regulation of the cell cycle: when, where, how and why? AB - Translational regulation contributes to the control of archetypal and specialized cell cycles, such as the meiotic and early embryonic cycles. Late meiosis and early embryogenesis unfold in the absence of transcription, so they particularly rely on translational repression and activation of stored maternal mRNAs. Here, we present examples of cell cycle regulators that are translationally controlled during different cell cycle and developmental transitions in model organisms ranging from yeast to mouse. Our focus also is on the RNA-binding proteins that affect cell cycle progression by recognizing special features in untranslated regions of mRNAs. Recent research highlights the significance of the cytoplasmic polyadenylation element-binding protein (CPEB). CPEB determines polyadenylation status, and consequently translational efficiency, of its target mRNAs in both transcriptionally active somatic cells as well as in transcriptionally silent mature Xenopus oocytes and early embryos. We discuss the role of CPEB in mediating the translational timing and in some cases spindle-localized translation of critical regulators of Xenopus oogenesis and early embryogenesis. We conclude by outlining potential directions and approaches that may provide further insights into the translational control of the cell cycle. PMID- 22084392 TI - Interleukin-1beta-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet's disease: an open-label pilot study. AB - OBJECTIVE: Uveitis and retinal vasculitis are sight-threatening manifestations of Behcet's disease with limited treatment options. This pilot study aimed to evaluate the safety, pharmacokinetics and clinical activity of XOMA 052 (gevokizumab), a recombinant humanised anti-interleukin 1beta antibody, in Behcet's disease patients with uveitis. METHODS: Patients with acute posterior or panuveitis, and/or retinal vasculitis, resistant to azathioprine and/or ciclosporin, and receiving 10 mg/day or less of prednisolone, were enrolled into the 98-day study. Immunosuppressive agents were discontinued at baseline. Patients received a single infusion of XOMA 052 (0.3 mg/kg). The safety and uveitis status and pharmacokinetics of XOMA 052 were evaluated. RESULTS: Seven patients enrolled and completed the study. No treatment-related adverse event was observed. XOMA 052 treatment was associated with rapid and durable clinical response in all patients. Complete resolution of intraocular inflammation was achieved in 4-21 days (median 14 days), with a median duration of response of 49 days (range 21-97 days); one patient remained exacerbation free throughout the study. CONCLUSIONS: Well tolerated, XOMA 052 resulted in a rapid onset and sustained reduction in intraocular inflammation in patients with resistant uveitis and retinal vasculitis. Moreover, the effect was observed despite discontinuation of immunosuppressive agents and without the need to increase corticosteroid dosages. PMID- 22084393 TI - IgG from patients with pulmonary arterial hypertension and/or systemic sclerosis binds to vascular smooth muscle cells and induces cell contraction. AB - OBJECTIVES: Pulmonary arterial hypertension (PAH) is characterised by remodelling of pulmonary arteries with enhanced vascular smooth muscle cell (VSMC) contraction, migration and proliferation. The authors investigated the presence of antibodies to human VSMCs in the serum of patients with systemic sclerosis with or without PAH and idiopathic PAH (iPAH). METHODS AND RESULTS: Antibodies to VSMCs were detected by immunofluorescence in sera from healthy controls and patients with scleroderma without PAH, scleroderma-associated PAH and iPAH. Serum IgG from these patients induced contraction of VSMCs in a collagen matrix in contrast with IgG from healthy controls. Several protein spots of interest and target antigens were identified by two-dimensional immunoblotting and MS, including stress-induced phosphoprotein 1 and alpha-enolase. Finally, antibodies to stress-induced phosphoprotein 1 were detected by ELISA in sera from 84%, 76% and 24% of patients with scleroderma without PAH, scleroderma-associated PAH and iPAH, respectively, compared with only 3% of healthy controls. CONCLUSION: The authors have identified IgG that binds to VSMCs in the serum of patients with scleroderma and iPAH. These antibodies may be pathogenic by modulating vascular contraction. The target antigens of these antibodies are stress-induced phosphoprotein 1 and alpha-enolase. PMID- 22084394 TI - Autophagy activation by rapamycin reduces severity of experimental osteoarthritis. AB - OBJECTIVES: Osteoarthritis is associated with cell death and extracellular matrix degradation in articular cartilage. Autophagy is an essential cellular homeostasis mechanism that was found to be deficient in ageing and osteoarthritic cartilage. This study determined whether pharmacological inhibition of the mammalian target of rapamycin (mTOR), a key inhibitor of autophagy, has disease modifying activity in experimental osteoarthritis. METHODS: Experimental osteoarthritis was induced by transection of the medial meniscotibial ligament and the medial collateral ligament in 2-month-old C57Bl/6 mice (n=36). Rapamycin (1 mg/kg weight/day) (n=18 mice) or dimethyl sulphoxide vehicle control (n=18 mice) was administered intraperitoneally for 10 weeks. Histopathological changes in articular cartilage and synovium were examined by using semiquantitative scoring systems. Rapamycin effects on mTOR signalling, autophagy, cartilage homeostasis and inflammation were analysed by immunohistochemistry and immunofluorescence staining. RESULTS: Rapamycin affected the mTOR signalling pathway in mouse knee joints as indicated by the inhibition of ribosomal protein S6 phosphorylation, a target of mTOR and activation of LC3, a main marker of autophagy. The severity of cartilage degradation was significantly (p<0.01) reduced in the rapamycin-treated group compared with the control group and this was associated with a significant (p<0.05) decrease in synovitis. Rapamycin treatment also maintained cartilage cellularity and decreased ADAMTS-5 and interleukin-1beta expression in articular cartilage. CONCLUSIONS: These results suggest that rapamycin, at least in part by autophagy activation, reduces the severity of experimental osteoarthritis. Pharmacological activation of autophagy may be an effective therapeutic approach for osteoarthritis. PMID- 22084395 TI - Anti-Ro52 monoclonal antibodies specific for amino acid 200-239, but not other Ro52 epitopes, induce congenital heart block in a rat model. AB - BACKGROUND: Congenital heart block (CHB) may develop in fetuses of women with anti-Ro/La autoantibodies following placental transfer of maternal autoantibodies and disruption of the fetal atrioventricular (AV) conduction system. Animal models of CHB currently rely on immunisation or transfer of anti-Ro/La antibodies purified from mothers of children with CHB, which does not allow precise identification of the disease-inducing antibody specificity. OBJECTIVE: To determine the ability of different anti-Ro52 monoclonal antibodies to induce cardiac electrophysiological abnormalities in vivo and affect the calcium homoeostasis of cardiomyocytes in vitro. METHODS: Monoclonal antibodies recognising different domains of Ro52 were generated and injected into pregnant rats, and ECG was recorded on newborn pups. Cultures of rat neonatal cardiomyocytes were established to assess the effect of the different anti-Ro52 monoclonal antibodies on calcium homoeostasis. RESULTS: First-degree AV block and bradycardia developed after maternal transfer of antibodies specific for amino acids 200-239 of Ro52 (p200), while pups exposed to antibodies targeting N- or C terminal epitopes of Ro52 did not show any electrocardiogram abnormalities. Addition of an anti-p200 antibody to cultured cardiomyocytes induced calcium dyshomoeostasis in a time- and dose-dependent manner, while addition of other Ro52 antibodies had no effect. CONCLUSION: These data for the first time show unambiguously that antibodies specific for amino acids 200-239 of Ro52 can induce cardiac conduction defects in the absence of other autoantibodies, and may therefore be the main initiators of cardiac pathology in the pool of anti-Ro52 antibodies in mothers of children with CHB. PMID- 22084396 TI - Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC 0941 triggers robust apoptosis and tumor growth inhibition. AB - Combinations of MAP/ERK kinase (MEK) and phosphoinositide 3-kinase (PI3K) inhibitors have shown promise in preclinical cancer models, leading to the initiation of clinical trials cotargeting these two key cancer signaling pathways. GDC-0973, a novel selective MEK inhibitor, and GDC-0941, a class I PI3K inhibitor, are in early stage clinical trials as both single agents and in combination. The discovery of these selective inhibitors has allowed investigation into the precise effects of combining inhibitors of two major signaling branches downstream of RAS. Here, we investigated multiple biomarkers in the mitogen-activated protein kinase (MAPK) and PI3K pathway to search for points of convergence that explain the increased apoptosis seen in combination. Using washout studies in vitro and alternate dosing schedules in mice, we showed that intermittent inhibition of the PI3K and MAPK pathway is sufficient for efficacy in BRAF and KRAS mutant cancer cells. The combination of GDC-0973 with the PI3K inhibitor GDC-0941 resulted in combination efficacy in vitro and in vivo via induction of biomarkers associated with apoptosis, including Bcl-2 family proapoptotic regulators. Therefore, these data suggest that continuous exposure of MEK and PI3K inhibitors in combination is not required for efficacy in preclinical cancer models and that sustained effects on downstream apoptosis biomarkers can be observed in response to intermittent dosing. PMID- 22084397 TI - Novel transcriptional targets of the SRY-HMG box transcription factor SOX4 link its expression to the development of small cell lung cancer. AB - The HMG box transcription factor SOX4 involved in neuronal development is amplified and overexpressed in a subset of lung cancers, suggesting that it may be a driver oncogene. In this study, we sought to develop this hypothesis including by defining targets of SOX4 that may mediate its involvement in lung cancer. Ablating SOX4 expression in SOX4-amplified lung cancer cells revealed a gene expression signature that included genes involved in neuronal development such as PCDHB, MYB, RBP1, and TEAD2. Direct recruitment of SOX4 to gene promoters was associated with their upregulation upon ectopic overexpression of SOX4. We confirmed upregulation of the SOX4 expression signature in a panel of primary lung tumors, validating their specific response by a comparison using embryonic fibroblasts from Sox4-deficient mice. Interestingly, we found that small cell lung cancer (SCLC), a subtype of lung cancer with neuroendocrine characteristics, was generally characterized by high levels of SOX2, SOX4, and SOX11 along with the SOX4-specific gene expression signature identified. Taken together, our findings identify a functional role for SOX genes in SCLC, particularly for SOX4 and several novel targets defined in this study. PMID- 22084398 TI - Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. AB - Altered metabolism in cancer cells is suspected to contribute to chemoresistance, but the precise mechanisms are unclear. Here, we show that intracellular ATP levels are a core determinant in the development of acquired cross-drug resistance of human colon cancer cells that harbor different genetic backgrounds. Drug-resistant cells were characterized by defective mitochondrial ATP production, elevated aerobic glycolysis, higher absolute levels of intracellular ATP, and enhanced HIF-1alpha-mediated signaling. Interestingly, direct delivery of ATP into cross-chemoresistant cells destabilized HIF-1alpha and inhibited glycolysis. Thus, drug-resistant cells exhibit a greater "ATP debt" defined as the extra amount of ATP needed to maintain homeostasis of survival pathways under genotoxic stress. Direct delivery of ATP was sufficient to render drug-sensitive cells drug resistant. Conversely, depleting ATP by cell treatment with an inhibitor of glycolysis, 3-bromopyruvate, was sufficient to sensitize cells cross resistant to multiple chemotherapeutic drugs. In revealing that intracellular ATP levels are a core determinant of chemoresistance in colon cancer cells, our findings may offer a foundation for new improvements to colon cancer treatment. PMID- 22084399 TI - Norathyriol suppresses skin cancers induced by solar ultraviolet radiation by targeting ERK kinases. AB - Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G(2)-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-kappaB during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer. PMID- 22084401 TI - Psychological stress and cytokine production in multiple sclerosis: correlation with disease symptomatology. AB - OBJECTIVE: Psychological variables such as perceived stress appear to play a role in symptom onset or disease exacerbation in multiple sclerosis (MS). The authors sought to determine if perceived stress is indeed associated with the expression of pro-inflammatory cytokines and disease symptoms in individuals with MS. To do so, the authors examined the relationships among disease symptomatology, perceived stress, and cytokine production from peripheral blood mononuclear cells in 42 outpatients with MS and 36 normative controls. METHOD: The authors drew peripheral blood from all subjects prior to the completion of a series of psychological instruments. The authors measured stress using the Perceived Stress scale and negative mood with the Profile of Mood States. Disease symptoms were measured using the Multiple Sclerosis Symptom Checklist. Cytokine production was induced separately by lipopolysaccharide and a combination of phytohemagglutinin and phorbol-12-myristate-13-acetate. RESULTS: In MS subjects, the induced production of interleukin (IL)-6 and IL-10 positively correlated with psychological stress, mood disturbance, and disease symptomatology. In contrast, psychological stress in control subjects significantly correlated with level of tumor necrosis factor-alpha (TNF-alpha), and mood disturbance correlated with levels of TNF-alpha and interferon-gamma. As well, compared to controls, MS subjects exhibited a significant fourfold increase in the production of IL-12. CONCLUSION: There is, in those with MS, a pattern of IL-6 and IL-10 production that correlates significantly with perceived stress and disease symptomatology. PMID- 22084400 TI - The brief family relationship scale: a brief measure of the relationship dimension in family functioning. AB - The Relationship dimension of the Family Environment Scale, which consists of the Cohesion, Expressiveness, and Conflict subscales, measures a person's perception of the quality of his or her family relationship functioning. This study investigates an adaptation of the Relationship dimension of the Family Environment Scale for Alaska Native youth. The authors tested the adapted measure, the Brief Family Relationship Scale, for psychometric properties and internal structure with 284 12- to 18-year-old predominately Yup'ik Eskimo Alaska Native adolescents from rural, remote communities. This non-Western cultural group is hypothesized to display higher levels of collectivism traditionally organized around an extended kinship family structure. Results demonstrate a subset of the adapted items function satisfactorily, a three-response alternative format provided meaningful information, and the subscale's underlying structure is best described through three distinct first-order factors, organized under one higher order factor. Convergent and discriminant validity of the Brief Family Relationship Scale was assessed through correlational analysis. PMID- 22084402 TI - Fatigue-related gene networks identified in CD14+ cells isolated from HIV infected patients: part II: statistical analysis. AB - PURPOSE: In limited samples of valuable biological tissues, univariate ranking methods of microarray analyses often fail to show significant differences among expression profiles. In order to allow for hypothesis generation, novel statistical modeling systems can be greatly beneficial. The authors applied new statistical approaches to solve the issue of limited experimental data to generate new hypotheses in CD14(+) cells of patients with HIV-related fatigue (HRF) and healthy controls. METHODOLOGY: We compared gene expression profiles of CD14(+) cells of nucleoside reverse transcriptase inhibitor (NRTI)-treated HIV patients with low versus high fatigue to healthy controls (n = 5 each). With novel Bayesian modeling procedures, the authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. Sparse association and liquid association networks further elucidated the possible biological pathways in which these genes are involved. RELEVANCE FOR NURSING PRACTICE: Genetic networks developed in a comprehensive Bayesian framework from small sample sizes allow nursing researchers to design future research approaches to address such issues as HRF. IMPLICATION FOR PRACTICE: The findings from this pilot study may take us one step closer to the development of useful biomarker targets for fatigue status. Specific and reliable tests are needed to diagnosis, monitor and treat fatigue and mitochondrial dysfunction. PMID- 22084403 TI - Pain and inflammation in women with early-stage breast cancer prior to induction of chemotherapy. AB - CONTEXT: Pain is a commonly experienced and distressing symptom in women with breast cancer (BCA), and recent evidence suggests that immune activation may be associated with pain and other co-occurring symptoms. However, no studies to date have explored the relationships among perceived pain and biomarkers of inflammation in women with early-stage BCA during the initial course of treatment. OBJECTIVES: The purpose of this research study was to examine the relationships among pro- and anti-inflammatory biomarkers and the presence of pain and other symptoms (anxiety, depression, fatigue, and sleep disorder) prior to induction of chemotherapy. METHOD: This was a secondary analysis of data that measured perceived symptoms, including the presence of pain and pain interference, and plasma levels of pro- and anti-inflammatory cytokines and C reactive protein (CRP) in women with early-stage BCA (N = 32) at 1 month postsurgery but prior to induction of chemotherapy. RESULTS: Women experiencing pain had significantly higher levels of CRP (p < .01), interleukin (IL) 13 (p < .02), and IL-7 (p < .02) and more pain interference (p < .01), depression (p < .01), and sleep disturbance (p < .01) compared to women reporting no pain. CONCLUSION: The presence of pain during the initial course of treatment in women with early-stage BCA was associated with significantly higher levels of CRP, IL 7, and IL-13, suggesting a potential role of immune activation in perceived pain. Further research to examine the precise effects of these biological factors in modulating pain is needed. Perceived pain was also associated with multiple co occurring symptoms, and this finding has important implications for symptom management. PMID- 22084404 TI - Lymphocyte recovery after breast cancer treatment and mindfulness-based stress reduction (MBSR) therapy. AB - OBJECTIVES: This randomized controlled trial was conducted to examine immune recovery following breast cancer (BC) therapy and evaluate the effect of mindfulness-based stress reduction therapy (MBSR) on immune recovery with emphasis on lymphocyte subsets, T cell activation, and production of T-helper 1 (Th1; interferon [IFN]-gamma) and T-helper 2 (Th2; interleukin-4 [IL-4]) cytokines. METHOD: Participants who completed the study consisted of 82 patients diagnosed with Stage 0-III BC, who received lumpectomy and adjuvant radiation +/- chemotherapy. Patients were randomized into an MBSR(BC) intervention program or a control (usual care) group. Immune cell measures were assessed at baseline and within 2 weeks after the 6-week intervention. The numbers and percentages of lymphocyte subsets, activated T cells, and Th1 and Th2 cells in peripheral blood samples were determined by immunostaining and flow cytometry. RESULTS: Immune subset recovery after cancer treatment showed positive associations with time since treatment completion. The B and natural killer (NK) cells were more susceptible than T cells in being suppressed by cancer treatment. Women who received MBSR(BC) had T cells more readily activated by the mitogen phytohemagglutinin (PHA) and an increase in the Th1/Th2 ratio. Activation was also higher for the MBSR(BC) group if <12 weeks from the end of treatment and women in MBSR(BC) <12 weeks had higher T cell count for CD4(+). CONCLUSION: MBSR(BC) promotes a more rapid recovery of functional T cells capable of being activated by a mitogen with the Th1 phenotype, whereas substantial recovery of B and NK cells after completion of cancer treatment appears to occur independent of stress-reducing interventions. PMID- 22084405 TI - Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity. AB - Ecotropic viral integration site 1 (Evi1), a transcription factor of the SET/PR domain protein family, is essential for the maintenance of hematopoietic stem cells (HSCs) in mice and is overexpressed in several myeloid malignancies. Here, we generate reporter mice in which an internal ribosome entry site (IRES)-GFP cassette is knocked-in to the Evi1 locus. Using these mice, we find that Evi1 is predominantly expressed in long-term HSCs (LT-HSCs) in adult bone marrow, and in the hematopoietic stem/progenitor fraction in the aorta-gonad-mesonephros, placenta, and fetal liver of embryos. In both fetal and adult hematopoietic systems, Evi1 expression marks cells with long-term multilineage repopulating activity. When combined with conventional HSC surface markers, sorting according to Evi1 expression markedly enhances purification of cells with HSC activity. Evi1 heterozygosity leads to marked impairment of the self-renewal capacity of LT HSCs, whereas overexpression of Evi1 suppresses differentiation and boosts self renewal activity. Reintroduction of Evi1, but not Mds1-Evi1, rescues the HSC defects caused by Evi1 heterozygosity. Thus, in addition to documenting a specific relationship between Evi1 expression and HSC self-renewal activity, these findings highlight the utility of Evi1-IRES-GFP reporter mice for the identification and sorting of functional HSCs. PMID- 22084406 TI - Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice. AB - Foxp3(+) regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor beta (TGF-beta) and retinoic acid. We found that the CD11c(high) dendritic cell fraction was the most potent at inducing high numbers of alloreactive Foxp3(+) cells. The induced CD4(+)CD25(+)Foxp3(+) cells appeared after extensive proliferation. When purified from the MLR, iT reg cells suppressed both primary and secondary MLR in vitro in an antigen-specific manner. After transfer into allogeneic mice, iT reg cells persisted for 6 mo and prevented graft versus host disease (GVHD) caused by co transferred CD45RB(hi) T cells. Similar findings were made when iT reg cells were transferred after onset of GVHD. The CNS2 intronic sequence of the Foxp3 gene in the persisting iT reg cells was as demethylated as the corresponding sequence of naturally occurring T reg cells. These results indicate that induced Foxp3(+) T reg cells, after proliferating and differentiating into antigen-specific suppressive T cells, can persist for long periods while suppressing a powerful inflammatory disease. PMID- 22084408 TI - Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo. AB - Plasmacytoid dendritic cells (pDCs) specialize in the secretion of type I interferons (IFN-I) and thus are considered critical mediators of antiviral responses. We recently reported that pDCs have a very early but limited and transient capacity to curtail viral infections. Additionally, pDC numbers are not sustained in human infections caused by Hepatitis B or C viruses (HBV and HCV) and HIV. Thus, the numbers and/or function of pDCs appear to be regulated during the course of viral infection. In this study, we show that splenic pDCs are reduced in vivo during several systemic viral infections and after administration of synthetic toll-like receptor ligands. We demonstrate that IFN-I, regardless of the source, contributes to this decline and mediates pDC death via the intrinsic apoptosis pathway. These findings demonstrate a feedback control mechanism by which IFN-I modulates pDC numbers, thus fine-tuning systemic IFN-I response to viruses. IFN-I-mediated control of pDCs may explain the loss of pDCs during human infections caused by HBV, HCV, or HIV and has important therapeutic implications for settings in which IFN-I is used to treat infections and autoimmune diseases. PMID- 22084407 TI - Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. AB - Skeletal muscle catabolism is a co-morbidity of many chronic diseases and is the result of systemic inflammation. Although direct inflammatory cytokine action on muscle promotes atrophy, nonmuscle sites of action for inflammatory mediators are less well described. We demonstrate that central nervous system (CNS)-delimited interleukin 1beta (IL-1beta) signaling alone can evoke a catabolic program in muscle, rapidly inducing atrophy. This effect is dependent on hypothalamic pituitary-adrenal (HPA) axis activation, as CNS IL-1beta-induced atrophy is abrogated by adrenalectomy. Furthermore, we identified a glucocorticoid responsive gene expression pattern conserved in models of acute and chronic inflammatory muscle atrophy. In contrast with studies suggesting that the direct action of inflammatory cytokines on muscle is sufficient to induce catabolism, adrenalectomy also blocks the atrophy program in response to systemic inflammation, demonstrating that glucocorticoids are requisite for this process. Additionally, circulating levels of glucocorticoids equivalent to those produced under inflammatory conditions are sufficient to cause profound muscle wasting. Together, these data suggest that a significant component of inflammation-induced muscle catabolism occurs indirectly via a relay in the CNS. PMID- 22084409 TI - IGSF4 is a novel TCR zeta-chain-interacting protein that enhances TCR-mediated signaling. AB - Immunoglobulin superfamily member 4 (IGSF4) is a known ligand of CRTAM, a receptor expressed in activated NKT and CD8(+) T cells, but its function in T cell immunity has not been elucidated. In this study, we show that IGSF4 directly interacts with the T cell receptor (TCR) zeta-chain and enhances TCR signaling by enhancing zeta-chain phosphorylation. Ectopic overexpression of IGSF4 enhances TCR-mediated T cell activation. In contrast, IGSF4 knockdown shows a dramatic decrease in markers associated with T cell activation compared with those in control small interfering RNA. The transmembrane domain is essential for TCR zeta chain association and clustering to the immunological synapse, and the ectodomain is associated with T cell interaction with antigen-presenting cells (APCs). IGSF4 deficient mice have impaired TCR-mediated thymocyte selection and maturation. Furthermore, these mice reveal attenuated effector T cell functions accompanied by defective TCR signaling. Collectively, the results indicate that IGSF4 plays a central role in T cell functioning by dual independent mechanisms, control of TCR signaling and control of T cell-APC interaction. PMID- 22084411 TI - Retraction. Foxp3-positive macrophages display immunosuppressive properties and promote tumor growth. PMID- 22084410 TI - Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor kappaB-mediated pathogenic pathways. AB - TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic lateral sclerosis (ALS). In this study, we report that TDP-43 and nuclear factor kappaB (NF-kappaB) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with p65 in glial and neuronal cells from ALS patients and mice expressing wild-type and mutant TDP-43 transgenes but not in cells from healthy individuals or nontransgenic mice. TDP-43 acted as a co-activator of p65, and glial cells expressing higher amounts of TDP-43 produced more proinflammatory cytokines and neurotoxic mediators after stimulation with lipopolysaccharide or reactive oxygen species. TDP-43 overexpression in neurons also increased their vulnerability to toxic mediators. Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-kappaB activity, reduced denervation in the neuromuscular junction and ALS disease symptoms. We propose that TDP-43 deregulation contributes to ALS pathogenesis in part by enhancing NF-kappaB activation and that NF-kappaB may constitute a therapeutic target for the disease. PMID- 22084412 TI - Prevention of venous thromboembolism using enoxaparin in day surgery: results of the SMART noninterventional study. AB - We aimed to confirm the results of randomized, controlled trials on enoxaparin prophylaxis in unselected patients undergoing day surgery. The primary end point was the incidence of thromboembolic events during prophylaxis and up to 48 hours thereafter. A total of 11 794 patients, consisting of 52.1% male with mean age of 49.2 +/- 15.7 were included. In all, 61.5% had no predisposing risk factors and 67.1% received no concomitant medication with the potential to increase bleeding. Patients were exposed to 20 mg (63.6%) and 40 mg (36.4%) of enoxaparin for a mean of 12.4 +/- 9.8 days. Forty-four patients (0.39%) had confirmed symptomatic deep venous thrombosis and 1 patient confirmed pulmonary embolism. Bleeding occurred in 3.47% of patients (3.29% minor bleeding). Differences between 20 and 40 mg enoxaparin were negligible. Adverse drug reactions were experienced by 3.1% of patients. The present study results demonstrate that it is effective and tolerable to use a risk stratified dose of 20 or 40 mg enoxaparin in patients undergoing day surgery. PMID- 22084413 TI - Prevalence of factor V Leiden G1691A, MTHFR C677T, and prothrombin G20210A among Asian Indian sickle cell patients. AB - The prevalence of factor V (FV) Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated among 90 sickle trait, 61 sickle homozygous, 75 sickle beta thalassemia, and 15 HbSD Asian Indian sickle cell patients. In all, 297 healthy controls were evaluated to compare the polymorphism frequency. The prevalence of FV Leiden heterozygous G>A were significant in the group (P = .02), while PRT G20210A polymorphism was not seen among patients as well as controls. However, an increased frequency of the MTHFR 677 C>T genotype was seen among patients as well as controls, but this was not statistically significant (P = .13). This suggested a low impact of inherited hypercoagulability risk factors in the pathogenesis of sickle cell disease and/or its complications. PMID- 22084414 TI - Ischemic stroke in the setting of chronic immune thrombocytopenia in an elderly patient--a therapeutic dilemma. AB - Chronic immune thrombocytopenia (ITP) carries a poor prognosis in the elderly patients. Increasing evidence proposes that a subgroup of patients with chronic ITP may be more susceptible to ischemic stroke. An 84-year-old Caucasian man with multiple ischemic stroke risk factors presented with acute onset of slurred speech, confusion, and unsteady gait. Physical examination and neurologic imaging were consistent with a new left thalamic infarct. Platelet counts ranged between 40 000 * 10(9)/L and 65 000 * 10(9) /L. Antiplatelet therapy for his newly acquired stroke was not initiated considering his low platelet counts and for mildly symptomatic thrombocytopenia, and the patient was discharged home. Both hematologic and neurologic guidelines for the management of chronic ITP and stroke have contradictory goals. Although anticoagulation is mandated in acute stroke, ITP causes low platelet counts that increase bleeding complications. PMID- 22084415 TI - Cl(-) concentration changes and desensitization of GABA(A) and glycine receptors. AB - Desensitization of ligand-gated ion channels plays a critical role for the information transfer between neurons. The current view on gamma-aminobutyric acid (GABA)(A) and glycine receptors includes significant rapid components of desensitization as well as cross-desensitization between the two receptor types. Here, we analyze the mechanism of apparent cross-desensitization between native GABA(A) and glycine receptors in rat central neurons and quantify to what extent the current decay in the presence of ligand is a result of desensitization versus changes in intracellular Cl(-) concentration ([Cl(-)](i)). We show that apparent cross-desensitization of currents evoked by GABA and by glycine is caused by changes in [Cl(-)](i). We also show that changes in [Cl(-)](i) are critical for the decay of current in the presence of either GABA or glycine, whereas changes in conductance often play a minor role only. Thus, the currents decayed significantly quicker than the conductances, which decayed with time constants of several seconds and in some cells did not decay below the value at peak current during 20-s agonist application. By taking the cytosolic volume into account and numerically computing the membrane currents and expected changes in [Cl(-)](i), we provide a theoretical framework for the observed effects. Modeling diffusional exchange of Cl(-) between cytosol and patch pipettes, we also show that considerable changes in [Cl(-)](i) may be expected and cause rapidly decaying current components in conventional whole cell or outside-out patch recordings. The findings imply that a reevaluation of the desensitization properties of GABA(A) and glycine receptors is needed. PMID- 22084417 TI - Psychodynamic Parenthood Therapy: a model for therapeutic work with parents and parenthood. AB - The approach to therapeutic work with parents in psychotherapy has been described in the literature in various ways but is not well defined. This article will give a short review of four main types of therapeutic work with parents: 1) Meeting to update and to accompany parents (Periodic update meeting with parents complementary to the child's psychotherapy), 2) Parental counseling (guidance), 3) Parent-child therapy (Relationship or dyadic therapy), 4) Family therapy. The claim is made that those approaches, important and effective as they are, do not deal with the parent as a main issue, and do not place enough attention on parenthood. This article offers a model referred to here as Psychodynamic Parenthood Therapy (PPT). PPT is a dynamic therapeutic intervention with parents based upon a contract focusing mainly on working on their parenthood. In general, a parent's negative feelings towards his parenthood or towards his child are some of the basic issues that can be helped by this approach. After clarifying the guidelines for choosing PPT, both the contract and the process itself will be explained. The process deals with parenthood: internalizations, unconscious feelings, intergenerational transmissions and parental identity. In comparison with other methods which do not deal specifically with parenthood, PPT will often lead to a meaningful and effective therapeutic result. PMID- 22084416 TI - Expression and characterization of the bacterial mechanosensitive channel MscS in Xenopus laevis oocytes. AB - We have successfully expressed and characterized mechanosensitive channel of small conductance (MscS) from Escherichia coli in oocytes of the African clawed frog, Xenopus laevis. MscS expressed in oocytes has the same single-channel conductance and voltage dependence as the channel in its native environment. Two hallmarks of MscS activity, the presence of conducting substates at high potentials and reversible adaptation to a sustained stimulus, are also exhibited by oocyte-expressed MscS. In addition to its ease of use, the oocyte system allows the user to work with relatively large patches, which could be an advantage for the visualization of membrane deformation. Furthermore, MscS can now be compared directly to its eukaryotic homologues or to other mechanosensitive channels that are not easily studied in E. coli. PMID- 22084418 TI - Problems with binary gender discourse: using context to promote flexibility and connection in gender identity. AB - Western society recognises male and female sex from physiological attributes, such as genitals and chromosomes. 'Gender' is the social and cultural expectation of how males and females should think, behave and how they should be treated by others (Diamond, 2002). Some children and adolescents experience distress, marginalization, and abuse associated with their gender identifications, preferences and behaviours, which are inconsistent with those expected of their biological sex. Often their families and society find gender non-conformity at best difficult, at worst offensive, distressing and intolerable. There is increasing focus on how mental health professionals work with difference in gender and sexual identity and recent publications highlight the shift from pathologizing transgender to a more 'identity-based' perspective, focussing more on the stigmatizing affects of the environment and the impact on the individual (Bockting, 2009). This article describes the challenges of binary gender discourse for young people and their wider contexts and considers how clinicians may more helpfully respond to avoid unhelpful binaries and so keep the young person in mind. The therapeutic aims of the UK Gender Identity Development Service (GIDS) for children and young people are considered and examples of our work provided. PMID- 22084419 TI - YeastBook: an encyclopedia of the reference eukaryotic cell. PMID- 22084420 TI - DNA sequence-mediated, evolutionarily rapid redistribution of meiotic recombination hotspots. AB - Hotspots regulate the position and frequency of Spo11 (Rec12)-initiated meiotic recombination, but paradoxically they are suicidal and are somehow resurrected elsewhere in the genome. After the DNA sequence-dependent activation of hotspots was discovered in fission yeast, nearly two decades elapsed before the key realizations that (A) DNA site-dependent regulation is broadly conserved and (B) individual eukaryotes have multiple different DNA sequence motifs that activate hotspots. From our perspective, such findings provide a conceptually straightforward solution to the hotspot paradox and can explain other, seemingly complex features of meiotic recombination. We describe how a small number of single-base-pair substitutions can generate hotspots de novo and dramatically alter their distribution in the genome. This model also shows how equilibrium rate kinetics could maintain the presence of hotspots over evolutionary timescales, without strong selective pressures invoked previously, and explains why hotspots localize preferentially to intergenic regions and introns. The model is robust enough to account for all hotspots of humans and chimpanzees repositioned since their divergence from the latest common ancestor. PMID- 22084421 TI - Yeast: an experimental organism for 21st Century biology. AB - In this essay, we revisit the status of yeast as a model system for biology. We first summarize important contributions of yeast to eukaryotic biology that we anticipated in 1988 in our first article on the subject. We then describe transformative developments that we did not anticipate, most of which followed the publication of the complete genomic sequence of Saccharomyces cerevisiae in 1996. In the intervening 23 years it appears to us that yeast has graduated from a position as the premier model for eukaryotic cell biology to become the pioneer organism that has facilitated the establishment of the entirely new fields of study called "functional genomics" and "systems biology." These new fields look beyond the functions of individual genes and proteins, focusing on how these interact and work together to determine the properties of living cells and organisms. PMID- 22084425 TI - Notch-1 and Notch-4 biomarker expression in triple-negative breast cancer. AB - Triple-negative breast cancer (TNBC) demonstrates lack of expression of hormone receptors and human epidermal growth factor receptor. However, there is no targeted therapy for TNBC. The authors analyzed 29 TNBC cases for Notch-1 and Notch-4 biomarker expression and subcellular location, Ki67 proliferation rate, and relevant clinical/survival data. Results demonstrated an unfavorable Ki67 rate in 90% of cases, Notch-1 expression in tumor and endothelial cells in 100% of cases, and Notch-4 expression in tumor cells in 73% of cases and endothelial cells in 100% of cases. Additionally, subcellular localization of Notch-1 and Notch-4 was predominantly nuclear and cytoplasmic. In conclusion, (a) the majority of TNBCs are high-grade infiltrating ductal carcinomas with high Ki67 proliferation rate and (b) both Notch-1 and Notch-4 receptors are overexpressed in tumor and vascular endothelial cells with subcellular localization different from that of hormone-positive breast cancer. Targeting Notch signaling with gamma secretase inhibitors should to be explored to further improve the survival rate of TNBC patients. PMID- 22084426 TI - Intra-abdominal clear-cell sarcoma: a report of 3 cases, including 1 case with unusual morphological features, and review of the literature. AB - Clear-cell sarcoma (CCS) is a soft-tissue neoplasm that morphologically resembles cutaneous malignant melanoma but has a distinct molecular profile. Gastrointestinal and intra-abdominal CCSs are very rare. Here, the authors present 3 cases of intra-abdominal CCS and review the literature. Of these cases, 2 involved the small bowel, and 1 involved the peritoneum. Cases 1 and 3 had the characteristic CCS morphology, but case 2 was morphologically unusual and therefore difficult to diagnose. It had relatively small cells with less prominence of clear cells; many pseudoglandular structures were also present. It also showed aberrant expression of epithelial membrane antigen (EMA). The other 2 cases also involved some diagnostic uncertainty and were therefore referred to specialized centers. The authors wish to emphasize the importance of molecular studies in making a conclusive diagnosis of intra-abdominal CCS. PMID- 22084427 TI - Cutaneous pseudolymphoma following tattoo application: report of two new cases of a potential lymphoma mimicker. AB - The authors report 2 cases of cutaneous pseudolymphoma that occurred in 2 young adult patients who referred for relentlessly growing nodules that appeared within 4 to 5 months after the application of a mercury-based tattoo. Systemic symptoms were not present and there was no evidence of lymph node enlargement. Clinically, both lesions were limited to the red, mercury-based areas of the tattoo. Microscopic examination featured a dense cellular infiltrate composed of polytypic T cells in the upper to mid-dermis, coupled with focal interface tissue reaction. Scattered macrophages contained finely granular particles in their cytoplasm. In addition, extracellular pigment particles were also recognized. Collections of epithelioid macrophages were present in both cases and were reminiscent of epithelioid granulomas. This study confirms evidence that, among skin diseases featuring a dense lymphoid infiltrate, cutaneous pseudolymphoma secondary to tattooing is a rare but not exceptional source of diagnostic challenges. PMID- 22084428 TI - "Fruiting bodies" of Aspergillus flavus: a rare finding in histopathology. PMID- 22084429 TI - Late recurrence of a seminoma of the testis with a poorly differentiated neuroendocrine carcinoma component. AB - The frequency and clinical relevance of late recurrences of testicular germ cells tumors (GCTs) has increased in the past few decades because of the improved survival of patients following the introduction, in the late 1970s, of cisplatin based chemotherapy. The late recurrences of GCT may take extremely variable features and occur several years after the primary tumor, making the diagnosis a challenge for both clinicians and pathologists. This study reports a case of a testicular seminoma that relapsed 28 years after surgery as an undifferentiated GCT with a heterologous component of neuroendocrine carcinoma that was initially misdiagnosed as a metastasis of primary intestinal tumor. PMID- 22084430 TI - Intestinal ancylostomiasis: an unusual histologic finding. PMID- 22084423 TI - Sporulation in the budding yeast Saccharomyces cerevisiae. AB - In response to nitrogen starvation in the presence of a poor carbon source, diploid cells of the yeast Saccharomyces cerevisiae undergo meiosis and package the haploid nuclei produced in meiosis into spores. The formation of spores requires an unusual cell division event in which daughter cells are formed within the cytoplasm of the mother cell. This process involves the de novo generation of two different cellular structures: novel membrane compartments within the cell cytoplasm that give rise to the spore plasma membrane and an extensive spore wall that protects the spore from environmental insults. This article summarizes what is known about the molecular mechanisms controlling spore assembly with particular attention to how constitutive cellular functions are modified to create novel behaviors during this developmental process. Key regulatory points on the sporulation pathway are also discussed as well as the possible role of sporulation in the natural ecology of S. cerevisiae. PMID- 22084422 TI - Transcriptional regulation in Saccharomyces cerevisiae: transcription factor regulation and function, mechanisms of initiation, and roles of activators and coactivators. AB - Here we review recent advances in understanding the regulation of mRNA synthesis in Saccharomyces cerevisiae. Many fundamental gene regulatory mechanisms have been conserved in all eukaryotes, and budding yeast has been at the forefront in the discovery and dissection of these conserved mechanisms. Topics covered include upstream activation sequence and promoter structure, transcription factor classification, and examples of regulated transcription factor activity. We also examine advances in understanding the RNA polymerase II transcription machinery, conserved coactivator complexes, transcription activation domains, and the cooperation of these factors in gene regulatory mechanisms. PMID- 22084431 TI - Leukemic priming of resting NK cells is killer Ig-like receptor independent but requires CD15-mediated CD2 ligation and natural cytotoxicity receptors. AB - Resting human NK cells require a two-stage activation process that we have previously described as "priming" and "triggering." NK-sensitive tumor cells provide both priming and triggering signals. NK-resistant tumors evade lysis, mostly by failure to prime; however, we recently reported a tumor cell line (CTV 1) that primes resting NK cells but fails to trigger lysis. In this article, we report two additional leukemia cell lines that prime NK cells but are resistant to lysis. Tumor-mediated NK priming is via CD2 binding to a ligand within CD15 on the tumor cell. NK-resistant RAJI cells became susceptible to NK lysis following transfection and expression of CD15. Blockade of CD15 on K562 cells or on CD15(+) RAJI cells significantly inhibited lysis, as did blockade of CD2 on resting NK cells. NK priming via CD2 induced CD16 shedding, releasing CD3zeta to the CD2, leading to its phosphorylation and the subsequent phosphorylation of linker for activation of T cells and STAT-5 and synthesis of IFN-gamma. Blockade of C-type lectin receptors significantly suppressed the tumor-mediated priming of NK cells, whereas blockade of Ig-superfamily-like receptors had no effect at the NK-priming stage. Tumor priming of resting NK cells was irrespective of HLA expression, and blockade of HLA-killer Ig-like receptor interactions did not influence the incidence or degree of priming. However, CD15-CD2 interactions were critical for NK priming and were required, even in the absence of HLA-mediated NK inhibition. Tumor-mediated priming led to a sustained primed state, and the activated NK cells retained the ability to lyse NK-resistant tumors, even after cryopreservation. PMID- 22084432 TI - Cutting edge: microRNA-181 promotes human NK cell development by regulating Notch signaling. AB - MicroRNAs (miRs) have recently been identified as important regulators of gene expression at the posttranscriptional level. Although it has clearly been established that miRs influence the ontogeny of several immune cell lineages, the role of individual miRs during NK cell development has not been described. In this study, we show that miR-181 expression levels have a profound impact on the development of human NK cells from CD34(+) hematopoietic progenitor cells and IFN gamma production in primary CD56(+) NK cells. We also demonstrate that nemo-like kinase (NLK), an inhibitor of Notch signaling, is a target of miR-181 in NK cells, and knockdown of NLK mirrors the developmental effect of miR-181 overexpression. We conclude that miR-181 promotes NK cell development, at least in part, through the suppression of NLK, providing an important link between miRs and Notch signaling. PMID- 22084433 TI - Expansion of functionally anergic CD21-/low marginal zone-like B cell clones in hepatitis C virus infection-related autoimmunity. AB - Homeostasis of peripheral B cell subsets is disturbed during chronic hepatitis C virus (HCV) infection, leading to the occurrence of autoimmunity and B cell lymphoproliferation. However, mechanisms by which HCV causes lymphoproliferation remain controversial. We report in this article on the elevated number of clonal CD21(-/low)IgM(+)CD27(+) marginal zone (MZ)-like B cells, which correlates with autoimmunity and lymphoproliferation in HCV patients. We found an increase in autoreactive BCRs using V(H)1-69 and V(H)4-34 genes in CD21(-/low) MZ B cells. CD21(-/low) MZ B cells showed impaired calcium-mediated signaling, did not upregulate activation markers, and did not proliferate in response to BCR triggering. CD21(-/low) MZ B cells also were prone to dying faster than their CD21(+) counterparts, suggesting that these B cells were anergic. CD21(-/low) MZ B cells, in contrast, remained responsive to TLR9 stimulation. Gene array analyses revealed the critical role of Early growth response 2 and Cbl-b in the induction of anergy. Therefore, HCV patients who display high frequencies of unresponsive CD21(-/low) MZ B cells are more susceptible to developing autoimmunity and/or lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells. PMID- 22084434 TI - Hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection. AB - Hepcidin is one of the regulators of iron metabolism. The expression of hepcidin is induced in spleens and livers of mice infected with pathogenic bacteria. Recent studies have indicated that serum hepcidin level is also increased in human subjects infected with Plasmodium falciparum. The mechanism of the regulation of hepcidin expression and its role in the infection of malaria remains unknown. In this study, we determined the expression of hepcidin in livers of mice infected with Plasmodium berghei. The expression of hepcidin in the liver was upregulated and downregulated during the early and late stages of malaria infection, respectively. Inflammation and erythropoietin, rather than the iron-sensing pathway, are involved in the regulation of hepcidin expression in livers of infected mice. Meanwhile, we investigated the effect of hepcidin on the survival of mice infected with P. berghei. Treatment of malaria-infected mice with anti-hepcidin neutralizing Abs promoted the rates of parasitemia and mortality. In contrast, lentiviral vector-mediated overexpression of hepcidin improved the outcome of P. berghei infection in mice. Our data demonstrate an important role of hepcidin in modulating the course and outcome of blood-stage malaria. PMID- 22084436 TI - Alloantibodies against MHC class I: a novel mechanism of neonatal pancytopenia linked to vaccination. AB - Fetal/neonatal alloimmune thrombocytopenia is a frequent disease in humans where alloantibodies against platelet Ags lead to platelet destruction and hemorrhage. Although a role in the disease for Abs against MHC has been suspected, this has not been formally demonstrated. Since 2007, a hemorrhagic syndrome due to thrombocytopenia and designated as bovine neonatal pancytopenia (BNP) has been recognized in calves in several European countries. An inactivated antiviral vaccine is strongly suspected to be involved in this syndrome because of its highly frequent use in the dams of affected calves. In this study, we show that BNP is an alloimmune disease, as we reproduced the signs by transferring serum Abs from vaccinated BNP dams into healthy neonatal calves. Ab specificity was strongly associated with the presence of allogeneic MHC class I Abs in the dams. MHC class I staining was also observed on Madin-Darby bovine kidney cells, a cell line related to the one used to produce the vaccine Ag. Our report emphatically demonstrates that alloimmunization against MHC class I is associated with a substantial risk of developing cytopenia-associated syndromes in neonates when a cell line of the same species is used to produce an inactivated vaccine injected into the mother. PMID- 22084435 TI - IL-15 regulates homeostasis and terminal maturation of NKT cells. AB - Semi-invariant NKT cells are thymus-derived innate-like lymphocytes that modulate microbial and tumor immunity as well as autoimmune diseases. These immunoregulatory properties of NKT cells are acquired during their development. Much has been learned regarding the molecular and cellular cues that promote NKT cell development, yet how these cells are maintained in the thymus and the periphery and how they acquire functional competence are incompletely understood. We found that IL-15 induced several Bcl-2 family survival factors in thymic and splenic NKT cells in vitro. Yet, IL-15-mediated thymic and peripheral NKT cell survival critically depended on Bcl-x(L) expression. Additionally, IL-15 regulated thymic developmental stage 2 to stage 3 lineage progression and terminal NKT cell differentiation. Global gene expression analyses and validation revealed that IL-15 regulated Tbx21 (T-bet) expression in thymic NKT cells. The loss of IL-15 also resulted in poor expression of key effector molecules such as IFN-gamma, granzyme A and C, as well as several NK cell receptors, which are also regulated by T-bet in NKT cells. Taken together, our findings reveal a critical role for IL-15 in NKT cell survival, which is mediated by Bcl-x(L), and effector differentiation, which is consistent with a role of T-bet in regulating terminal maturation. PMID- 22084437 TI - An MHC class Ib-restricted CD8+ T cell response to lymphocytic choriomeningitis virus. AB - Conventional MHC class Ia-restricted CD8(+) T cells play a dominant role in the host response to virus infections, but recent studies indicate that T cells with specificity for nonclassical MHC class Ib molecules may also participate in host defense. To investigate the potential role of class Ib molecules in anti-viral immune responses, K(b-/-)D(b-/-)CIITA(-/-) mice lacking expression of MHC class Ia and class II molecules were infected with lymphocytic choriomeningitis virus (LCMV). These animals have a large class Ib-selected CD8(+) T cell population and they were observed to mediate partial (but incomplete) virus clearance during acute LCMV infection as compared with K(b-/-)D(b-/-)beta(2)-microglobulin(-/-) mice that lack expression of both MHC class Ia and class Ib molecules. Infection was associated with expansion of splenic CD8(+) T cells and induction of granzyme B and IFN-gamma effector molecules in CD8(+) T cells. Partial virus clearance was dependent on CD8(+) cells. In vitro T cell restimulation assays demonstrated induction of a population of beta(2)-microglobulin-dependent, MHC class Ib restricted CD8(+) T cells with specificity for viral Ags and yet to be defined nonclassical MHC molecules. MHC class Ib-restricted CD8(+) T cell responses were also observed after infection of K(b-/-)D(b-/-)mice despite the low number of CD8(+) T cells in these animals. Long-term infection studies demonstrated chronic infection and gradual depletion of CD8(+) T cells in K(b-/-)D(b-/-)CIITA(-/-) mice, demonstrating that class Ia molecules are required for viral clearance. These findings demonstrate that class Ib-restricted CD8(+) T cells have the potential to participate in the host immune response to LCMV. PMID- 22084438 TI - Transfer of regulatory properties from tolerogenic to proinflammatory dendritic cells via induced autoreactive regulatory T cells. AB - Infectious tolerance is a term generally assigned to the process through which regulatory T cells (Tregs) transfer immunoregulatory properties to other T cells. In this study, we demonstrated that a similar process applies to human dendritic cells (DCs), albeit through a different mechanism. We induced and cloned proinsulin-specific Tregs using tolerogenic DCs and investigated mechanisms by which induced Ag-specific regulatory T cells (iaTregs) endorse the suppressive effects. iaTregs expressed FOXP3, programmed death-1, and membrane-bound TGF-beta and upregulated IL-10 and CTLA-4 after stimulation with the cognate Ag. The iaTregs suppressed effector T cells only when both encountered the cognate Ags on the same APCs (linked suppression). This occurred independently of IL-10, TGF beta, programmed death-1, or CTLA-4. Instead, iaTregs used a granzyme B-mediated mechanism to kill B cells and monocytes, whereas proinflammatory DCs that resisted being killed were induced to upregulate the inhibitory receptors B7 (family) homolog 3 and ICOS ligand. These re-educated mature monocyte-derived dendritic cells (mDCs) suppressed effector T cells and induced IL-10-producing cells from the naive T cell pool. Our data indicated that human tolerogenic DCs confer infectious tolerance by inducing Ag-specific Tregs, which, in turn, re educate proinflammatory mature DCs into DCs with regulatory properties. PMID- 22084440 TI - Cutting edge: loss of alpha4 integrin expression differentially affects the homing of Th1 and Th17 cells. AB - The neutralization of alpha4 integrin is currently used as treatment in several autoimmune diseases and is thought to prevent the entry of most immune cells in target tissues. In this study, we showed that selective deletion of alpha4 integrin in T cells did not prevent but delayed the development of experimental autoimmune encephalomyelitis. Whereas both Th1 and Th17 cells infiltrate the CNS of wild-type mice, T cells present in the CNS of mice lacking alpha4 integrin were mainly enriched in Th17 cells, suggesting that this T cell subset uses other integrins to access the CNS. In contrast, alpha4 integrin expression is important for Th1 cells to enter the CNS and for the stability of their Th1-associated genetic program. Therefore, our data suggest that anti-alpha4 integrin Ab treatment may be more efficient in the treatment of Th1- rather than Th17 mediated disease. PMID- 22084439 TI - Neutralizing IL-6 reduces human arterial allograft rejection by allowing emergence of CD161+ CD4+ regulatory T cells. AB - Perioperative injuries to an allograft exacerbate graft rejection, which in humans is primarily mediated by effector memory T cells. IL-6 transcripts in human coronary artery segments rapidly increase posttransplantation into immunodeficient mouse hosts compared with those of pretransplant specimens and fall dramatically by 30 d. Adoptive transfer of human PBMCs allogeneic to the artery 2 d postoperatively results in T cell infiltrates and intimal expansion 4 wk later. Ab neutralization of human IL-6 reduces the magnitude of intimal expansion and total T cell infiltration but increases the relative expression of CD161 while decreasing other Th17 markers. Coculture of MHC class II-expressing human endothelial cells (ECs) with allogeneic CD4(+) memory T cells results in T cell activation and EC secretion of IL-6. Neutralizing IL-6 in primary allogeneic T cell-EC cocultures results in enhanced T cell proliferation of CD161(+) CD4(+) T cells, reduces total T cell proliferation upon restimulation in secondary cultures (an effect dependent on CD161(+) T cells), increases expression of FOXP3 in CD161(+) T cells, and generates T cells that suppress proliferation of freshly isolated T cells. These data suggest that IL-6 released from injured allograft vessels enhances allogeneic T cell infiltration and intimal expansion in a model of human allograft rejection by inhibiting an increase in CD161(+) regulatory T cells. PMID- 22084441 TI - Rat and mouse CD94 associate directly with the activating transmembrane adaptor proteins DAP12 and DAP10 and activate NK cell cytotoxicity. AB - Signaling by the CD94/NKG2 heterodimeric NK cell receptor family has been well characterized in the human but has remained unclear in the mouse and rat. In the human, the activating receptor CD94/NKG2C associates with DAP12 by an ionic bond between oppositely charged residues within the transmembrane regions of NKG2C and DAP12. The lysine residue responsible for DAP12 association is absent in rat and mouse NKG2C and -E, raising questions about signaling mechanisms in these species. As a possible substitute, rat and mouse NKG2C and -E contain an arginine residue in the transition between the transmembrane and stalk regions. In this article, we demonstrate that, similar to their human orthologs, NKG2A inhibits, whereas NKG2C activates, rat NK cells. Redirected lysis assays using NK cells transfected with a mutated NKG2C construct indicated that the activating function of CD94/NKG2C did not depend on the transmembrane/stalk region arginine residue. Flow cytometry and biochemical analysis demonstrated that both DAP12 and DAP10 can associate with rat CD94/NKG2C. Surprisingly, DAP12 and DAP10 did not associate with NKG2C but instead with CD94. These associations depended on a transmembrane lysine residue in CD94 that is unique to rodents. Thus, in the mouse and rat, the ability to bind activating adaptor proteins has been transferred from NKG2C/E to the CD94 chain as a result of mutation events in both chains. Remarkable from a phylogenetic perspective, this sheds new light on the evolution and function of the CD94/NKG2 receptor family. PMID- 22084442 TI - Granzyme B regulates antiviral CD8+ T cell responses. AB - CTLs and NK cells use the perforin/granzyme cytotoxic pathway to kill virally infected cells and tumors. Human regulatory T cells also express functional granzymes and perforin and can induce autologous target cell death in vitro. Perforin-deficient mice die of excessive immune responses after viral challenges, implicating a potential role for this pathway in immune regulation. To further investigate the role of granzyme B in immune regulation in response to viral infections, we characterized the immune response in wild-type, granzyme B deficient, and perforin-deficient mice infected with Sendai virus. Interestingly, granzyme B-deficient mice, and to a lesser extent perforin-deficient mice, exhibited a significant increase in the number of Ag-specific CD8(+) T cells in the lungs and draining lymph nodes of virally infected animals. This increase was not the result of failure in viral clearance because viral titers in granzyme B deficient mice were similar to wild-type mice and significantly less than perforin-deficient mice. Regulatory T cells from WT mice expressed high levels of granzyme B in response to infection, and depletion of regulatory T cells from these mice resulted in an increase in the number of Ag-specific CD8(+) T cells, similar to that observed in granzyme B-deficient mice. Furthermore, granzyme B deficient regulatory T cells displayed defective suppression of CD8(+) T cell proliferation in vitro. Taken together, these results suggest a role for granzyme B in the regulatory T cell compartment in immune regulation to viral infections. PMID- 22084443 TI - Structural basis of diverse peptide accommodation by the rhesus macaque MHC class I molecule Mamu-B*17: insights into immune protection from simian immunodeficiency virus. AB - The MHC class I molecule Mamu-B*17 has been associated with elite control of SIV infection in rhesus macaques, akin to the protective effects described for HLA B*57 in HIV-infected individuals. In this study, we determined the crystal structures of Mamu-B*17 in complex with eight different peptides corresponding to immunodominant SIV(mac)239-derived CD8(+) T cell epitopes: HW8 (HLEVQGYW), GW10 (GSHLEVQGYW), MW9 (MHPAQTSQW), QW9 (QTSQWDDPW), FW9 (FQWMGYELW), MF8 (MRHVLEPF), IW9 (IRYPKTFGW), and IW11 (IRYPKTFGWLW). The structures reveal that not only P2, but also P1 and P3, can be used as N-terminal anchor residues by Mamu-B*17 restricted peptides. Moreover, the N-terminal anchor residues exhibit a broad chemical specificity, encompassing basic (H and R), bulky polar aliphatic (Q), and small (T) residues. In contrast, Mamu-B*17 exhibits a very narrow preference for aromatic residues (W and F) at the C terminus, similar to that displayed by HLA-B*57. Flexibility within the whole peptide-binding groove contributes to the accommodation of these diverse peptides, which adopt distinct conformations. Furthermore, the unusually large pocket D enables compensation from other peptide residues if P3 is occupied by an amino acid with a small side chain. In addition, residues located at likely TCR contact regions present highly flexible conformations, which may impact TCR repertoire profiles. These findings provide novel insights into the structural basis of diverse peptide accommodation by Mamu B*17 and highlight unique atomic features that might contribute to the protective effect of this MHC I molecule in SIV-infected rhesus macaques. PMID- 22084445 TI - Lactate: a metabolic key player in cancer. AB - Increased glucose uptake and accumulation of lactate, even under normoxic conditions (i.e., aerobic glycolysis or the Warburg Effect), is a common feature of cancer cells. This phenomenon clearly indicates that lactate is not a surrogate of tumor hypoxia. Tumor lactate can predict for metastases and overall survival of patients, as shown by several studies of different entities. Metastasis of tumors is promoted by lactate-induced secretion of hyaluronan by tumor-associated fibroblasts that create a milieu favorable for migration. Lactate itself has been found to induce the migration of cells and cell clusters. Furthermore, radioresistance has been positively correlated with lactate concentrations, suggesting an antioxidative capacity of lactate. Findings on interactions of tumor metabolites with immune cells indicate a contribution of lactate to the immune escape. Furthermore, lactate bridges the gap between high lactate levels in wound healing, chronic inflammation, and cancer development. Tumor cells ensure sufficient oxygen and nutrient supply for proliferation through lactate-induced secretion of VEGF, resulting in the formation of new vessels. In summary, accumulation of lactate in solid tumors is a pivotal and early event in the development of malignancies. The determination of lactate should enter further clinical trials to confirm its relevance in cancer biology. PMID- 22084446 TI - Tyrosine isomers mediate the classical phenomenon of concomitant tumor resistance. AB - Concomitant tumor resistance (CR) is a phenomenon originally described in 1906 in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although recent studies have indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In this study, we identify this serum factor as tyrosine in its meta and ortho isoforms. In three different murine models of cancer that generate CR, both meta-tyrosine and ortho-tyrosine inhibited tumor growth. In addition, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isoforms were mediated, in part, by early inhibition of mitogen activated protein/extracellular signal-regulated kinase pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors, an issue of pivotal importance to oncologists and their patients. PMID- 22084447 TI - Neurobehavioral effects of acute exposure to isoparaffinic and cycloparaffinic hydrocarbons. AB - This article reports neurobehavioral tests in rats with C5-C11 isoparaffinic and cycloparaffinic hydrocarbons. Testing, conducted shortly after exposure, evaluated the effects in several domains including clinical effects, motor activity, functional observations, and visual discrimination performance. Isopentane and cyclopentane did not produce any evidence of acute central nervous system (CNS) effects at levels up to 20 000 mg/m(3). A C(6)/C(7) mixed cycloparaffinic solvent produced minor, reversible changes in latency to response in visual discrimination testing at 14 000 mg/m(3); the no-effect level was 4200 mg/m(3). A C(8) isoparaffin produced no effects at 14 000 mg/m(3), the highest level tested. A C(9)/C(11) isoparaffinic solvent produced minor acute CNS effects at 5000 mg/m(3), with 1500 mg/m(3) as the no-effect level. A C(10) cycloparaffinic solvent did not produce any statistically significant CNS effects at 5000 mg/m(3). These studies were designed to provide data that may be useful in setting occupational exposure limits for C5-C11 isoparaffinic and cycloparaffinic hydrocarbons. PMID- 22084448 TI - Time course of treatment effect of OROS(r) methylphenidate in children with ADHD. AB - OBJECTIVE: The authors evaluated the time course of the treatment effect of Osmotic-Release Oral System methylphenidate (OROS((r)) MPH) HCl (Concerta((r)), Raritan, NJ) CII in children with ADHD. METHOD: Data were combined from two double-blind, randomized, placebo-controlled, cross-over, analog classroom studies in children (9-12 years) with ADHD. Participants received an individualized dose of placebo or OROS((r)) MPH on two laboratory school days. Permanent Product Math Test and Swanson, Kotkin, Agler, M-Flynn, and Pelham scores were evaluated 0.5 hr before dosing and 1, 2, 4, 10, 11, and 12.5 hr post dose. Analysis used a repeated-measures mixed model. RESULTS: Treatment effects were present at all postdose assessment points (p < .0001 for all comparisons, n = 139). Adverse events were similar to previous reports for OROS((r)) MPH. CONCLUSION: A robust treatment effect occurred with OROS((r)) MPH; onset was at 1 hr and persisted for at least 12.5 hr after dosing. PMID- 22084449 TI - Health advocate: what do we expect of family physicians? PMID- 22084452 TI - Should patients be entitled to cesarean section on demand?: Yes. PMID- 22084451 TI - Prescription opioid abuse: what is the real problem and how do we fix it? PMID- 22084453 TI - Should patients be entitled to cesarean section on demand?: No. PMID- 22084455 TI - Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 1: general population. AB - OBJECTIVE: To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. QUALITY OF EVIDENCE: Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. MAIN MESSAGE: Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. CONCLUSION: Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety. PMID- 22084456 TI - Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 2: special populations. AB - OBJECTIVE: To provide family physicians with a practical clinical summary of opioid prescribing for specific populations based on recommendations from the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain. QUALITY OF EVIDENCE: Researchers for the guideline conducted a systematic review of the literature, focusing on reviews of the effectiveness and safety of opioids in specific populations. MAIN MESSAGE: Family physicians can minimize the risks of overdose, sedation, misuse, and addiction through the use of strategies tailored to the age and health status of patients. For patients at high risk of addiction, opioids should be reserved for well-defined nociceptive or neuropathic pain conditions that have not responded to first-line treatments. Opioids should be titrated slowly, with frequent dispensing and close monitoring for signs of misuse. Suspected opioid addiction is managed with structured opioid therapy, methadone or buprenorphine treatment, or abstinence-based treatment. Patients with mood and anxiety disorders tend to have a blunted analgesic response to opioids, are at higher risk of misuse, and are often taking sedating drugs that interact adversely with opioids. Precautions similar to those for other high-risk patients should be employed. The opioid should be tapered if the patient's pain remains severe despite an adequate trial of opioid therapy. In the elderly, sedation, falls, and overdose can be minimized through lower initial doses, slower titration, benzodiazepine tapering, and careful patient education. For pregnant women taking daily opioid therapy, the opioids should be slowly tapered and discontinued. If this is not possible, they should be tapered to the lowest effective dose. Opioid-dependent pregnant women should receive methadone treatment. Adolescents are at high risk of opioid overdose, misuse, and addiction. Patients with adolescents living at home should store their opioid medication safely. Adolescents rarely require long-term opioid therapy. CONCLUSION: Family physicians must take into consideration the patient's age, psychiatric status, level of risk of addiction, and other factors when prescribing opioids for chronic pain. PMID- 22084457 TI - Prophylactic use of antimalarials during pregnancy. AB - QUESTION: Some of my pregnant patients wish to travel to malaria-endemic regions. Are there medications that can be used safely during pregnancy for malaria prophylaxis? ANSWER: Pregnant women should avoid travel to malaria-endemic areas if possible. However, if travel cannot be avoided, measures to prevent mosquito bites, along with an effective chemoprophylaxis regimen, should be implemented. Chloroquine or hydroxychloroquine are considered safe to use in all trimesters of pregnancy. Mefloquine is the agent of choice for chloroquine-resistant areas, and evidence suggests it is not associated with an increased risk to the fetus. Although the atovaquone-proguanil drug combination is not currently recommended for use during pregnancy, limited data suggest that it is not harmful to the fetus. Doxycycline and primaquine are not recommended during pregnancy. PMID- 22084458 TI - Update on acute otitis media in children younger than 2 years of age. AB - QUESTION: As concern about antimicrobial resistance grows, I am aware of the need to reduce unnecessary antibiotic treatment; however, in my practice I see many children with acute otitis media (AOM) and this is the most common reason I prescribe antibiotics. Most of these children are young and otherwise healthy, and I am uncertain about when to prescribe antibiotics and when to endorse "watchful waiting." Which children will benefit from antibiotic treatment? ANSWER: Current Canadian guidelines recommend all children younger than 2 years of age with otalgia due to AOM and fever greater than 39 degrees C be considered for treatment with amoxicillin. Watchful waiting is indicated only for children older than 6 months with mild-to-moderate AOM. Recent evidence suggests young children with a definitive diagnosis of AOM will benefit from antibiotics and experience fewer treatment failures compared with placebo, regardless of the severity of otitis. These studies do not challenge watchful waiting directly, and determining which children will improve spontaneously remains an enigma. PMID- 22084459 TI - Delayed antibiotic prescriptions for URTIs. PMID- 22084460 TI - Common cold. PMID- 22084461 TI - Dermacase. Can you identify this condition? Nevus anemicus. PMID- 22084462 TI - Ophthaproblem. Can you identify this condition? Temporal arteritis. PMID- 22084463 TI - Part 12. Systematic desensitization. PMID- 22084466 TI - Advocating for the advocate. PMID- 22084464 TI - Age equity in different models of primary care practice in Ontario. AB - OBJECTIVE: To assess whether the model of service delivery affects the equity of the care provided across age groups. DESIGN: Cross-sectional study. SETTING: Ontario. PARTICIPANTS: One hundred thirty-seven practices, including traditional fee-for-service practices, salaried community health centres (CHCs), and capitation-based family health networks and health service organizations. MAIN OUTCOME MEASURES: To compare the quality of care across age groups using multilevel linear or logistic regressions. Health service delivery measures and health promotion were assessed through patient surveys (N = 5111), which were based on the Primary Care Assessment Tool, and prevention and chronic disease management were assessed, based on Canadian recommendations for care, through chart abstraction (N = 4108). RESULTS: Older individuals reported better health service delivery in all models. This age effect ranged from 1.9% to 5.7%, and was larger in the 2 capitation-based models. Individuals aged younger than 30 years attending CHCs had more features of disadvantage (ie, living below the poverty line and without high school education) and were more likely than older individuals to report discussing at least 1 health promotion subject at the index visit. These differences were deemed an appropriate response to greater needs in these younger individuals. The prevention score showed an age-sex interaction in all models, with adherence to recommended care dropping with age for women. These results are largely attributable to the fact that maneuvers recommended for younger women are considerably more likely to be performed than other maneuvers. Chronic disease management scores showed an inverted U relationship with age in fee-for-service practices, family health networks, and health service organizations but not in CHCs. CONCLUSION: The salaried model might have an organizational structure that is more conducive to providing appropriate care across age groups. The thrust toward adopting capitation-based payment is unlikely to have an effect on age disparities. PMID- 22084467 TI - Continuity: middle C--a very good place to start. PMID- 22084470 TI - Cesarean section on demand: is it a fad or an advance in medical practice? PMID- 22084471 TI - Addiction medicine and substance abuse care. PMID- 22084472 TI - Comprehensive treatment program for pregnant substance users in a family medicine clinic. AB - PROBLEM BEING ADDRESSED: Substance use during pregnancy is a substantial public health problem and a risk factor for poor neonatal outcomes. Prenatal care is often provided in high-risk pregnancy units, separate from addiction treatment. OBJECTIVE OF PROGRAM: To provide comprehensive prenatal care and addiction treatment in a family medicine setting. DESCRIPTION OF PROGRAM: The Toronto Centre for Substance Use in Pregnancy (T-CUP) is a family medicine-based program in a large urban city in Ontario. The T-CUP program comprises an interdisciplinary team using a one-stop access model to provide comprehensive services for pregnant women with a history of alcohol or drug abuse, including prenatal and postnatal medical care, addiction counseling, and assistance with complex psychosocial needs. EVALUATION: A retrospective chart review was performed, including charts for 121 women who received care at T-CUP from August 2000 to January 2006. Women demonstrated a high compliance rate with prenatal care attendance. Most women reported reduction in a variety of drug use categories. Significant differences were found especially among women who presented earlier in their pregnancies (P < .05). As a result, neonatal outcomes were satisfactory and approximately 75% of newborns were discharged home in the care of their mothers. CONCLUSION: Pregnant substance-using women have positive maternal and infant health outcomes when they receive comprehensive care in a family medicine setting. PMID- 22084473 TI - Characteristics of chronic pain patients in a rural teaching practice. AB - OBJECTIVE: To describe the characteristics of chronic noncancer pain (CNCP) patients taking oxycodone or its derivatives in a rural teaching practice. DESIGN: Characteristics of CNCP patients taking oxycodone over a 5-year period (September 2003 to September 2008) were compared with those of patients not taking opioid medications using a retrospective chart audit. SETTING: A rural teaching practice in southwestern Ontario. PARTICIPANTS: A total of 103 patients taking chronic oxycodone therapy for CNCP and a random sample of 104 patients not taking opioid medication. MAIN OUTCOME MEASURES: Number of visits, health problems, sex, and previous history of addiction and mental illness. RESULTS: Patients with CNCP taking oxycodone had significantly more health problems (P < .001), including drug and tobacco addictions. They had more than 3 times as many clinic visits during the same period of time as patients not taking opioid medication (mean of 39.0 vs 12.8 visits, P < .001). CONCLUSION: Patients with CNCP in this rural teaching practice had significantly more health issues (P < .001) and were more likely to have a history of addiction than other patients were. They created more work with significantly more visits over the same period compared with the comparison group. PMID- 22084474 TI - Narcotic-exposed neonates in a First Nations population in northwestern Ontario: incidence and implications. AB - OBJECTIVE: To document the incidence of neonatal abstinence syndrome (NAS) and the rate of narcotic use during pregnancy in northwestern Ontario, where narcotic abuse is a growing social and medical problem. DESIGN: Retrospective chart review. SETTING: The Sioux Lookout Meno Ya Win Health Centre catchment area in northwestern Ontario. PARTICIPANTS: Mothers and neonates for the 482 live births that took place in the 18-month study period (January 2009 to June 2010). MAIN OUTCOME MEASURES: Maternal drug use and neonatal outcomes were documented. RESULTS: The incidence of narcotic (oxycodone) abuse during pregnancy increased from a low of 8.4% at the beginning of the study period to a high of 17.2% by mid 2010. Narcotic-using mothers were more likely to also use nicotine and alcohol, to have premature deliveries, and to be episodic users. Narcotic-exposed neonates experienced NAS 29.5% of the time; daily maternal use was associated with a higher rate of NAS (66.0%). While all infants roomed in with their mothers, exposed infants were more likely to require transfer to a tertiary care nursery. Infants with severe NAS were treated with oral morphine and had significantly longer hospital stays compared with the entire cohort (4.5 vs 1.5 days, P = .004). Narcotic abuse during pregnancy in our region is not currently associated with increased rates of HIV or hepatitis C infection, as intravenous route of administration is less common at present than intranasal and oral ingestion. CONCLUSION: Narcotic abuse during pregnancy is a considerable problem in First Nations communities in northwestern Ontario. Community-based initiatives need to be developed to address this issue, and medical and nursing staff need to develop surveillance, assessment, and therapeutic responses. Passive neonatal addiction and withdrawal result from maternal narcotic use during pregnancy. Rates of opioid use among pregnant Canadian women are unknown. PMID- 22084475 TI - Pharmacists' experiences with dispensing opioids: provincial survey. AB - OBJECTIVE: To explore pharmacists' beliefs, practices, and experiences regarding opioid dispensing. DESIGN: Mailed survey. SETTING: The province of Ontario. PARTICIPANTS: A total of 1011 pharmacists selected from the Ontario College of Pharmacists' registration list. MAIN OUTCOME MEASURES: Pharmacists' experiences with opioid-related adverse events (intoxication and aberrant drug-related behaviour) and their interactions with physicians. RESULTS: A total of 652 pharmacists returned the survey, for a response rate of 64%. Most (86%) reported that they were concerned about several or many of their patients who were taking opioids; 36% reported that at least 1 patient was intoxicated from opioids while visiting their pharmacies within the past year. Reasons for opioid intoxication included the patient taking more than prescribed (84%), the patient using alcohol or sedating drugs along with the opioid (69.9%), or the prescribed dose being too high (34%). Participants' most common concerns in the 3 months before the survey were patients coming in early for prescription refills, suspected double doctoring, and requests for replacement doses for lost medication (reported frequently by 39%, 12%, and 16% of respondents, respectively). Pharmacists were concerned about physician practices, such as prescribing benzodiazepines along with opioids. Pharmacists reported difficulty in reaching physicians directly by telephone (43%), and indicated that physicians frequently did not return their calls promptly (28%). The strategies rated as most helpful for improving opioid dispensing were a provincial prescription database and opioid prescribing guidelines. CONCLUSION: Pharmacists commonly observe opioid intoxication and aberrant drug-related behaviour in their patients but have difficulty communicating their concerns to physicians. System-wide strategies are urgently needed to improve the safety of opioid prescribing and to enhance communication between physicians and pharmacists. PMID- 22084481 TI - Return of the "intimate outsider": current trends and issues in family nursing research revisited. AB - This article reviews family nursing research published from 1996 to 2011. This is a follow-up to a review published in the Journal of Family Nursing in 1995. Findings from the first review are compared with this one, trends in family nursing scholarship are identified, and predictions and suggestions for future directions are offered. The latest generation of family nursing scholarship is conceptually and methodologically sound, and there is evidence of more multidisciplinary and interdisciplinary research conducted by family nursing researchers. Scholars are paying more attention to issues of diversity and family context at present than in the past, although there are still aspects of diversity that need more attention. Strong research programs in family nursing exist worldwide; an international synergism has helped promote rapid expansion of family nursing research and theory development. A vigorous movement to promote research to practice initiatives and greater attention to family interventions are exciting developments. PMID- 22084479 TI - Frequent and widespread vascular abnormalities in human signal transducer and activator of transcription 3 deficiency. AB - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) deficiency is responsible for autosomal dominant hyperimmunoglobulin E syndrome, characterized by recurrent bacterial and fungal infections, connective tissue abnormalities, hyperimmunoglobulin E, and Th17 lymphopenia. Although vascular abnormalities have been reported in some patients, the prevalence, characteristics, and etiology of these features have yet to be described. METHODS AND RESULTS: We prospectively screened 21 adult STAT3-deficient patients [corrected] (median age, 26 years; range, 17-44 years) [corrected] for vascular abnormalities. We explored the entire arterial vasculature with whole-body magnetic resonance imaging angiography, coronary multislice computed tomography, and echo-tracking-based imaging specifically for the [corrected] carotid arteries. We also assayed for serum biomarkers of inflammation and endothelial dysfunction. Finally, we studied murine models of aortic aneurysm in the presence and absence of inhibitors of STAT3-dependent signaling. Ninety-five percent of patients showed brain abnormalities (white matter hyperintensities, lacunar lesions suggestive of ischemic infarcts, and atrophy). We reported peripheral and brain artery abnormalities in 84% of the patients and detected coronary artery abnormalities in 50% of the patients. The most frequent vascular abnormalities were ectasia and aneurysm. The carotid intima-media thickness was markedly decreased, with a substantial increase in circumferential wall stress, indicating the occurrence of hypotrophic arterial remodeling in this STAT3-deficient population. Systemic inflammatory biomarker levels correlated poorly with the vascular phenotype. In vivo inhibition of STAT3 signaling or blockade of IL-17A resulted in a marked increase in aneurysm severity and fatal rupture in mouse models. CONCLUSIONS: Vascular abnormalities are highly prevalent in patients with STAT3 deficiency. This feature is consistent with the greater susceptibility to vascular aneurysm observed after inhibition of STAT3-dependent signaling in mouse models. PMID- 22084482 TI - Contending and adapting every day: norwegian parents' lived experience of having a child with ADHD. AB - Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood disorders, and little attention has been paid to the parents and their experiences. The aim of this study was to gain a deeper understanding of the Norwegian parents' lived experiences of having a child with an ADHD diagnosis. A descriptive design using phenomenological approach was chosen as the research method. Individual qualitative interviews with nine parents, who were members of the ADHD Association, were conducted. The interviews were analyzed according to Colaizzi's method. The essential structure of the parents' experiences was Contending and Adapting Every Day-Windsurfing in unpredictable waters which was embedded in the interrelated main themes: Maintaining the Self and Parenthood, and Interacting With the Surrounding World. Being the parent of a child with ADHD is a demanding situation. Nurses need to address the needs of these parents and focus on the family unit. PMID- 22084483 TI - Misconceptions about missed conceptions: the meanings of emergency contraceptive pills use among young adult couples. AB - Emergency contraceptive pills (ECP) are a safe and efficacious backup method of birth control. Despite widespread availability, ECP is underutilized by young women. While partner level of involvement has been shown to influence contraceptive behavior, there is a dearth of knowledge regarding any possible association between partner influence and ECP use. To better understand the reasons for the seemingly underuse of ECP, a grounded theory study was conducted to elucidate the relationship of couple dynamics and knowledge of, attitudes toward, and decision making regarding the use of ECP in coupled young adults. Consistent with contemporary constructivist grounded theory methods, several categories were identified including the meanings associated with ECP use. This article presents an elaboration of this particular finding. The meanings that participants ascribed to ECP use represented a continuum of value attributes regarding ethics, safety, efficacy, and responsibility. PMID- 22084484 TI - Family functioning of child-rearing Japanese families on family-accompanied work assignments in Hong Kong. AB - Although the number of employees on overseas assignments accompanied by their families has increased steadily, little is known about the effects of this experience on family functioning. Japanese families on family-accompanied assignments living in Hong Kong were compared with families living in Japan (consisting of 135 and 248 paired partners, respectively). Applying an ecological framework, family functioning was examined using the Feetham Family Functioning Survey-Japanese (FFFS-J). Japanese wives living in Hong Kong rated family functioning lower, particularly in the area of "relationship between family and family members." Between paired marital partners living in Hong Kong, the level of satisfaction in the area of "relationship between family and society" was significantly lower for wives than for husbands. This study provides application of the family ecological framework in families in a multicultural environment and identifies potential areas for family assessment and intervention that may of interest to health care professionals who care for families living away from their home countries. PMID- 22084486 TI - International Family Nursing Association (IFNA): Update and Membership Recruitment. PMID- 22084488 TI - Tolerance and effects of FK506 (tacrolimus) on nerve regeneration: a pilot study. AB - In adults, the outcome of nerve suture and nerve autograft remains generally unsatisfactory. FK506 (tacrolimus), an immunosuppressant drug used in transplantation, has been reported in animal studies to enhance nerve regeneration. In hand transplantation patients, nerve regeneration was unexpectedly good and rapid, and this observation has been attributed to FK506. The present Phase II experiment investigated the tolerance to FK506 after nerve suture or autograft, and the potential effects of the drug on axonal regeneration. Following strict criteria, five patients were included in this study. Within 7 days of nerve repair (median, ulnar and sciatic transections), patients received FK506 (aiming for blood concentrations between 5 and 8 ng/ml) for a total duration of 60 days. The patients were carefully followed with clinical and biological monitoring in order to detect side-effects. A clinical and electrophysiological assessment of the effect of FK506 on nerve regeneration was conducted. No undesirable side-effect was observed during or after FK506 treatment, but one non-compliant patient discontinued treatment. There was no evident improvement of sensory, motor or functional recovery at the end of the follow-up period (average duration 39.8 months), as compared to the expected clinical result without treatment. Although statistically non-significant, FK506 seemed to accelerate the progression of the Hoffmann-Tinel sign, but without impact on the final result. PMID- 22084489 TI - Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis. AB - BACKGROUND: Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV 6). Their role in MS clinical course is less clear, however. METHODS: Prospective cohort of 198 persons with clinically definite MS, followed 2002-5, and serum samples obtained from all subjects at study entry to measure anti-HHV-6 and anti EBV (Epstein-Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis; association with disability/progression evaluated using linear regression or multilevel mixed effects linear regression. RESULTS: For the 145 persons with relapsing-remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend (p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores; however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males. DISCUSSION: These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing-remitting MS clinical course. PMID- 22084490 TI - Effects of 3 weeks' whole body vibration training on muscle strength and functional mobility in hospitalized persons with multiple sclerosis. AB - BACKGROUND: Exercise therapy in persons with multiple sclerosis (MS) is effective for improving muscle strength and functional mobility. OBJECTIVE: To investigate, in MS patients attending an in-patient rehabilitation program, the additional effects of a 3-week exercise program, performed on a whole body vibration platform, on muscle strength and functionality. METHODS: Median Expanded Disability Status Scale (EDSS) of participating patients was 5.5. This randomized controlled trial differentiated a MS control group (n = 17) and two exercise groups performing exercises on a vibration platform (WBV-full group, n = 20) and on the platform additionally covered by a damping mat (WBV-light group, n = 18). Exercise groups performed, during 10 training sessions, six static and dynamic exercises standing on a platform vibrating at high frequency and low amplitude. Isometric muscle strength of quadriceps, hamstrings, tibialis anterior and gluteus medius was measured with a hand-held dynamometer. Functional mobility was measured with Berg Balance Scale (BBS), 3-minute walk test and Timed Get up and Go test. RESULTS: Eight drop-outs occurred in the exercise groups (WBV-full = 4, WBV-light = 4), but were unrelated to WBV as type of intervention. Across groups, significant time effects were found for all muscle groups. For maximal quadriceps and hamstrings muscle strength, interaction effects were found with post-hoc tests indicating exercise group-significant improvements in the WBV-full group only. Significant time effects were found for all functional tests. Improvements on the BBS and 3-minute walk test were larger in training than in control groups, but no significant interactions were found. CONCLUSIONS: A 3-week exercise program on a vibration plate significantly improved muscle strength, but not functionality, in persons with MS. PMID- 22084491 TI - Incidence and causes for syringe driver site reactions in palliative care: A prospective hospice-based study. AB - BACKGROUND: Syringe drivers are routinely used in palliative care for the subcutaneous infusion of drugs for pain and symptom control. Local site reactions occurring at the site of infusion can lead to patient discomfort and the potential for sub-optimal symptom control. AIM: The aim of this study was to investigate whether there was a correlation between drugs administered subcutaneously via a syringe driver and the incidence of syringe driver site reactions, further linking this to time to syringe driver site reaction. DESIGN: Prospective quantitative data collection of syringe driver use for 170 hospice inpatients. SETTING/PARTICIPANTS: Specialist palliative care inpatient facility in the UK. Syringe driver recording forms were retrieved from case notes of consecutive patients who received medication via a syringe driver. RESULTS: An association between the presence of cyclizine and levomepromazine and the incidence of syringe driver site reactions was identified. A marked difference in incidence of syringe driver site reaction was observed between the two study centres (26.5% vs. 7.7%). Although baseline patient characteristics were comparable, a difference in practice between the centres was identified, i.e. use of parenteral cannulae. An association between the time a syringe driver was in situ and the occurrence of a syringe driver site reaction was also demonstrated. CONCLUSIONS: Recommendations can be made for the frequency of syringe driver site changes based on which drugs are in use. Incidental findings from the study have been used to change practice at the hospice study site, with regard to choice of parenteral cannulae. PMID- 22084492 TI - The impact of body-part-naming training on the accuracy of imitative performances in 2- to 3-year-old children. AB - A series of three experiments explored the relationship between 3-year-old children's ability to name target body parts and their untrained matching of target hand-to-body touches. Nine participants, 3 per experiment, were presented with repeated generalized imitation tests in a multiple-baseline procedure, interspersed with step-by-step training that enabled them to (i) tact the target locations on their own and the experimenter's bodies or (ii) respond accurately as listeners to the experimenter's tacts of the target locations. Prompts for on task naming of target body parts were also provided later in the procedure. In Experiment 1, only tact training followed by listener probes were conducted; in Experiment 2, tacting was trained first and listener behavior second, whereas in Experiment 3 listener training preceded tact training. Both tact and listener training resulted in emergence of naming together with significant and large improvements in the children's matching performances; this was true for each child and across most target gestures. The present series of experiments provides evidence that naming--the most basic form of self-instructional behavior--may be one means of establishing untrained matching as measured in generalized imitation tests. This demonstration has a bearing on our interpretation of imitation reported in the behavior analytic, cognitive developmental, and comparative literature. PMID- 22084493 TI - Contextual influences on resistance to disruption in children with intellectual disabilities. AB - Training context can influence resistance to disruption under differing reinforcement schedules. With nonhumans, when relatively lean and rich reinforcement schedules are experienced in the context of a multiple schedule, greater resistance is found in the rich than the lean component, as described by behavioral momentum theory. By contrast, when the schedules are experienced in separated blocks of sessions (i.e., as single schedules), resistance is not consistently greater in either component. In the current study, two groups of 6 children with intellectual disabilities responded to stimuli presented in relatively lean or rich components. For both, reinforcers were delivered according to the same variable-interval reinforcement schedule; additionally, the rich component included the delivery of response-independent reinforcers. The Within group was trained on a multiple schedule in which lean and rich components alternated regularly within sessions; the Blocked group was trained on two single schedules in which sessions with either the lean or rich schedule were conducted in successive blocks. Disruption tests presented a concurrently available alternative stimulus disrupter signaling the availability of tangible reinforcers. All 6 Within participants showed greater resistance to disruption in the rich component, consistent with behavioral momentum theory. By contrast, there was no consistent or significant difference in resistance for Blocked participants. This finding is potentially relevant to the development of interventions in applied settings, where such interventions often approximate single schedules and include response-independent reinforcers. PMID- 22084494 TI - Emergent identity matching after successive matching training, I: reflexivity or generalized identity. AB - This research investigated the source of an ostensible reflexivity effect in pigeons reported by Sweeney and Urcuioli (2010). In Experiment 1, pigeons learned two symmetrically reinforced symbolic successive matching tasks (hue-form and form-hue) using red-green and triangle-horizontal line stimuli. They differed in their third concurrently trained baseline task: form-form matching with stimuli appearing in the symbolic tasks (triangle and horizontal) for one group versus hue-hue matching with stimuli not appearing in the symbolic tasks (blue and white) for the other. During subsequent nonreinforced probe tests, all pigeons in the former group and most pigeons in the latter group responded more to the comparisons on matching than on nonmatching red-green probes. In Experiment 2, the latter group was tested on nonreinforced form-form probes. One of the 4 pigeons responded significantly more to the comparisons on matching than on nonmatching triangle-horizontal probes. These data are consistent with generalized identity and at least one other interpretation of the reflexivity results and question the functional stimulus assumption of Urcuioli's (2008) stimulus-class theory. PMID- 22084495 TI - Whatever gave you that idea? False memories following equivalence training: a behavioral account of the misinformation effect. AB - The misinformation effect is a term used in the cognitive psychological literature to describe both experimental and real-world instances in which misleading information is incorporated into an account of an historical event. In many real-world situations, it is not possible to identify a distinct source of misinformation, and it appears that the witness may have inferred a false memory by integrating information from a variety of sources. In a stimulus equivalence task, a small number of trained relations between some members of a class of arbitrary stimuli result in a large number of untrained, or emergent relations, between all members of the class. Misleading information was introduced into a simple memory task between a learning phase and a recognition test by means of a match-to-sample stimulus equivalence task that included both stimuli from the original learning task and novel stimuli. At the recognition test, participants given equivalence training were more likely to misidentify patterns than those who were not given such training. The misinformation effect was distinct from the effects of prior stimulus exposure, or partial stimulus control. In summary, stimulus equivalence processes may underlie some real-world manifestations of the misinformation effect. PMID- 22084496 TI - A mechanism for reducing delay discounting by altering temporal attention. AB - Rewards that are not immediately available are discounted compared to rewards that are immediately available. The more a person discounts a delayed reward, the more likely that person is to have a range of behavioral problems, including clinical disorders. This latter observation has motivated the search for interventions that reduce discounting. One surprisingly simple method to reduce discounting is an "explicit-zero" reframing that states default or null outcomes. Reframing a classical discounting choice as "something now but nothing later" versus "nothing now but more later" decreases discount rates. However, it is not clear how this "explicit-zero" framing intervention works. The present studies delineate and test two possible mechanisms to explain the phenomenon. One mechanism proposes that the explicit-zero framing creates the impression of an improving sequence, thereby enhancing the present value of the delayed reward. A second possible mechanism posits an increase in attention allocation to temporally distant reward representations. In four experiments, we distinguish between these two hypothesized mechanisms and conclude that the temporal attention hypothesis is superior for explaining our results. We propose a model of temporal attention whereby framing affects intertemporal preferences by modifying present bias. PMID- 22084497 TI - Some determinants of remote behavioral history effects in humans. AB - Undergraduates were exposed to a series of reinforcement schedules: first, to a fixed-ratio (FR) schedule in the presence of one stimulus and to a differential reinforcement-of-low-rate (DRL) schedule in the presence of another (multiple FR DRL training), then to a fixed-interval (FI) schedule in the presence of a third stimulus (FI baseline), next to the FI schedule under the stimuli previously correlated with the FR and DRL schedules (multiple FI FI testing), and, finally, to a single session of the multiple FR DRL schedule again (multiple FR DRL testing). Response rates during the multiple FI FI schedule were higher under the former FR stimulus than under the former DRL stimulus. This effect of remote histories was prolonged when either the number of FI-baseline sessions was small or zero, or the time interval between the multiple FR DRL training and the multiple FI FI testing was short. Response rates under these two stimuli converged with continued exposure to the multiple FI FI schedule in most cases, but quickly differentiated when the schedule returned to the multiple FR DRL. PMID- 22084498 TI - Relational discrimination by pigeons in a go/no-go procedure with compound stimuli: a methodological note. AB - A go/no-go procedure with compound stimuli typically establishes emergent behavior that parallels in structure and typical outcome that of conventional tests for symmetric, transitive, and equivalence relations in normally capable adults. The present study employed a go/no-go compound stimulus procedure with pigeons. During training, pecks to two-component compounds A1B1, A2B2, B1C1, and B2C2 were followed by food. Pecks to compounds A1B2, A2B1, B1C2, and B2C1 re started the 30-s stimulus presentation interval. The absence of pecking to those compounds for 30 s ended the trial. Subsequent tests presented these components in new spatial arrangements and/or in recombinative compounds that together corresponded to conventional tests of symmetry, transitivity, and equivalence: B1A1, B2A2, C1B1, C2B2, A1C1, A2C2, C1A1, C2A2 vs. B1A2, B2A1, C1B2, C2B1, A1C2, A2C1, C1A2, C2A1 (positive vs. negative instances of symmetric, transitive, and equivalence relations). On tests for symmetric relations, all pigeons behaved in a manner consistent with training on both positive instances (i.e., by responding) and on negative instances (i.e., by not responding). By contrast, the pigeons' behavior on tests for transitivity and equivalence was inconsistent with baseline training, thus failing to show the recombinative discrimination performance that is typical of normally capable humans when trained and tested using the go/no-go procedure with compound stimuli. PMID- 22084499 TI - Delay discounting: I'm a k, you're a k. AB - Delay discounting is the decline in the present value of a reward with delay to its receipt. Across a variety of species, populations, and reward types, value declines hyperbolically with delay. Value declines steeply with shorter delays, but more shallowly with longer delays. Quantitative modeling provides precise measures to characterize the form of the discount function. These measures may be regarded as higher-order dependent variables, intervening variables, or hypothetical constructs. I suggest the degree of delay discounting may be a personality trait. In the end, the ontological status of measures of delay discounting is irrelevant. Whatever delay discounting may be, its study has provided the field of behavior analysis and other areas measures with robust generality and predictive validity for a variety of significant human problems. Research on moderating the degree of delay discounting has the potential to produce substantial societal benefits. PMID- 22084501 TI - Global action on social determinants of health. PMID- 22084502 TI - Social determinants of health: practical solutions to deal with a well-recognized issue. PMID- 22084504 TI - Behind the "Glasgow effect". AB - Michael Reid reports on how the Scottish city is tackling the stark inequities in its people's health. PMID- 22084506 TI - A decade towards better health in Chile. AB - In 1990, after 17 years of dictatorship, Chile started rebuilding its political system with a focus on improving social conditions and health. A recent study of the last 10 years shows some positive results. Irene Helmke reports. PMID- 22084505 TI - Tackling social factors to save lives in India. AB - Health inequalities persist amid a booming economy. Patralekha Chatterjee reports. PMID- 22084507 TI - Dealing with the big picture in Australia. AB - Public health challenges cannot be tackled by departments of health alone. Matthew Heath reports on how the state government of South Australia is taking a new approach. PMID- 22084508 TI - Brazil calls for pact on social factors to improve health. AB - As host of the World Conference on Social Determinants of Health on 19-21 October 2011, Brazil has shown its commitment to tackling social factors to improve people's health and well-being. Minister of Health Alexandre Padilha talks to the WHO Bulletin about what his country has done in this respect and his hopes for the conference. PMID- 22084509 TI - Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008. AB - OBJECTIVE: To carry out a descriptive analysis of mesothelioma deaths reported worldwide between 1994 and 2008. METHODS: We extracted data on mesothelioma deaths reported to the World Health Organization mortality database since 1994, when the disease was first recorded. We also sought information from other English-language sources. Crude and age-adjusted mortality rates were calculated and mortality trends were assessed from the annual percentage change in the age adjusted mortality rate. FINDINGS: In total, 92,253 mesothelioma deaths were reported by 83 countries. Crude and age-adjusted mortality rates were 6.2 and 4.9 per million population, respectively. The age-adjusted mortality rate increased by 5.37% per year and consequently more than doubled during the study period. The mean age at death was 70 years and the male-to-female ratio was 3.6:1. The disease distribution by anatomical site was: pleura, 41.3%; peritoneum, 4.5%; pericardium, 0.3%; and unspecified sites, 43.1%. The geographical distribution of deaths was skewed towards high-income countries: the United States of America reported the highest number, while over 50% of all deaths occurred in Europe. In contrast, less than 12% occurred in middle- and low-income countries. The overall trend in the age-adjusted mortality rate was increasing in Europe and Japan but decreasing in the United States. CONCLUSION: The number of mesothelioma deaths reported and the number of countries reporting deaths increased during the study period, probably due to better disease recognition and an increase in incidence. The different time trends observed between countries may be an early indication that the disease burden is slowly shifting towards those that have used asbestos more recently. PMID- 22084510 TI - Excess child mortality after discharge from hospital in Kilifi, Kenya: a retrospective cohort analysis. AB - OBJECTIVE: To explore excess paediatric mortality after discharge from Kilifi District Hospital, Kenya, and its duration and risk factors. METHODS: Hospital and demographic data were used to describe post-discharge mortality and survival probability in children aged < 15 years, by age group and clinical syndrome. Cox regression models were developed to identify risk factors. FINDINGS: In 2004 2008, approximately 111,000 children were followed for 555,000 person-years. We analysed 14,971 discharges and 535 deaths occurring within 365 days of discharge. Mortality was higher in the post-discharge cohort than in the community cohort (age-adjusted rate ratio, RR: 7.7; 95% confidence interval, CI: 6.6-8.9) and declined little over time. An increased post-discharge mortality hazard was found in children aged < 5 years with the following: weight-for-age Z score < -4 (hazard ratio, HR: 6.5); weight-for-age Z score > -4 but < -3 (HR: 3.4); hypoxia (HR: 2.3); bacteraemia (HR: 1.8); hepatomegaly (HR: 2.3); jaundice (HR: 1.8); hospital stay > 13 days (HR: 1.8). Older age was protective (reference < 1 month): 6-23 months, HR: 0.8; 2-4 years, HR: 0.6. Children with at least one risk factor accounted for 545 (33%) of the 1655 annual discharges and for 39 (47%) of the 83 discharge-associated deaths. CONCLUSION: Hospital admission selects vulnerable children with a sustained increased risk of dying. The risk factors identified provide an empiric basis for effective outpatient follow-up. PMID- 22084511 TI - Childhood and adult mortality from unintentional falls in India. AB - OBJECTIVE: To estimate fall-related mortality by type of fall in India. METHODS: The authors analysed unintentional injury data from the ongoing Million Death Study from 2001-2003 using verbal autopsy and coding of all deaths in accordance with the International statistical classification of diseases and related health problems, tenth revision, in a nationally representative sample of 1.1 million homes throughout the country. FINDINGS: Falls accounted for 25% (2003/8023) of all deaths from unintentional injury and were the second leading cause of such deaths. An estimated 160,000 fall-related deaths occurred in India in 2005; of these, nearly 20,000 were in children aged 0-14 years. The unintentional-fall related mortality rate (MR) per 100,000 population was 14.5 (99% confidence interval, CI: 13.7-15.4). Rates were similar for males and females at 14.9 (99% CI: 13.7-16.0) and 14.2 (99% CI: 13.1-15.4) per 100,000 population, respectively. People aged 70 years or older had the highest mortality rate from unintentional falls (MR: 271.2; 99% CI: 249.0-293.5), and the rate was higher among women (MR: 281; 99% CI: 249.7-311.3). Falls on the same level were the most common among older adults, whereas falls from heights were more common in younger age groups. CONCLUSION: In India, unintentional falls are a major public health problem that disproportionately affects older women and children. The contexts in which these falls occur and the resulting morbidity and disability need to be better understood. In India there is an urgent need to develop, test and implement interventions aimed at preventing falls. PMID- 22084512 TI - Risk factors for Mycobacterium tuberculosis infection among children in Greenland. AB - OBJECTIVE: To examine the risk factors for Mycobacterium tuberculosis infection (MTI) among Greenlandic children for the purpose of identifying those at highest risk of infection. METHODS: Between 2005 and 2007, 1797 Greenlandic schoolchildren in five different areas were tested for MTI with an interferon gamma release assay (IGRA) and a tuberculin skin test (TST). Parents or guardians were surveyed using a standardized self-administered questionnaire to obtain data on crowding in the household, parents' educational level and the child's health status. Demographic data for each child--i.e. parents' place of birth, number of siblings, distance between siblings (next younger and next older), birth order and mother's age when the child was born--were also extracted from a public registry. Logistic regression was used to check for associations between these variables and MTI, and all results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Children were considered to have MTI if they tested positive on both the IGRA assay and the TST. FINDINGS: The overall prevalence of MTI was 8.5% (152/1797). MTI was diagnosed in 26.7% of the children with a known TB contact, as opposed to 6.4% of the children without such contact. Overall, the MTI rate was higher among Inuit children (OR: 4.22; 95% CI: 1.55-11.5) and among children born less than one year after the birth of the next older sibling (OR: 2.48; 95% CI: 1.33-4.63). Self-reported TB contact modified the profile to include household crowding and low mother's education. Children who had an older MTI-positive sibling were much more likely to test positive for MTI themselves (OR: 14.2; 95% CI: 5.75-35.0) than children without an infected older sibling. CONCLUSION: Ethnicity, sibling relations, number of household residents and maternal level of education are factors associated with the risk of TB infection among children in Greenland. The strong household clustering of MTI suggests that family sources of exposure are important. PMID- 22084513 TI - Preoperative visual acuity among cataract surgery patients and countries' state of development: a global study. AB - OBJECTIVE: To describe the preoperative surgical case mix among patients undergoing cataract extraction and explore associations between case mix, country level of development (as measured by the Human Development Index, HDI) and cataract surgery rates (CSRs). METHODS: Ophthalmologists in 50 countries were invited to join the newly-established International Eye Research Network and asked to complete a web-based questionnaire about their eye hospitals. Those who complied received a data collection form for recording demographic and clinical data on 100 consecutive patients about to undergo cataract surgery. Countries were ranked into five HDI categories and multivariable regression was used to explore associations. FINDINGS: Ophthalmologists at 112 eye hospitals (54% of them nongovernmental) in 50 countries provided data on 11,048 cataract procedures over 9 months in 2008. Patients whose visual acuity (VA) before surgery was < 6/60 in the better eye comprised 47% of the total case mix in poorly developed countries and 1% in developed countries (P < 0.001). Overall, 72% of the eyes undergoing surgery had a VA < 6/60. Very low VA before cataract surgery was strongly associated with poor development at the country level and inversely associated with national CSR. CONCLUSION: The proportion of patients with very poor preoperative VA is a simple indicator that can be easily measured periodically to monitor progress in ophthalmological services. Additionally, the internet can be an effective tool for developing and supporting an ophthalmological research network capable of providing a global snapshot of service activity, particularly in developing countries. PMID- 22084514 TI - Health-care-associated infection in Africa: a systematic review. AB - OBJECTIVE: To assess the epidemiology of endemic health-care-associated infection (HAI) in Africa. METHODS: Three databases (PubMed, the Cochrane Library, and the WHO regional medical database for Africa) were searched to identify studies published from 1995 to 2009 on the epidemiology of HAI in African countries. No language restriction was applied. Available abstract books of leading international infection control conferences were also searched from 2004 to 2009. FINDINGS: The eligibility criteria for inclusion in the review were met by 19 articles, only 2 of which met the criterion of high quality. Four relevant abstracts were retrieved from the international conference literature. The hospital-wide prevalence of HAI varied between 2.5% and 14.8%; in surgical wards, the cumulative incidence ranged from 5.7% to 45.8%. The largest number of studies focused on surgical site infection, whose cumulative incidence ranged from 2.5% to 30.9%. Data on causative pathogens were available from a few studies only and highlighted the importance of gram-negative rods, particularly in surgical site infection and ventilator-associated pneumonia. CONCLUSION: Limited information is available on the endemic burden of HAI in Africa, but our review reveals that its frequency is much higher than in developed countries. There is an urgent need to identify and implement feasible and sustainable approaches to strengthen HAI prevention, surveillance and control in Africa. PMID- 22084516 TI - Action on social determinants of health is essential to tackle noncommunicable diseases. PMID- 22084515 TI - Estimated global incidence of Japanese encephalitis: a systematic review. AB - OBJECTIVE: To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts. METHODS: Thirty-two areas endemic for JE in 24 Asian and Western Pacific countries were sorted into 10 incidence groups on the basis of published data and expert opinion. Population-based surveillance studies using laboratory-confirmed cases were sought for each incidence group by a computerized search of the scientific literature. When no eligible studies existed for a particular incidence group, incidence data were extrapolated from related groups. FINDINGS: A total of 12 eligible studies representing 7 of 10 incidence groups in 24 JE endemic countries were identified. Approximately 67,900 JE cases typically occur annually (overall incidence: 1.8 per 100,000), of which only about 10% are reported to the World Health Organization. Approximately 33,900 (50%) of these cases occur in China (excluding Taiwan) and approximately 51,000 (75%) occur in children aged 0-14 years (incidence: 5.4 per 100,000). Approximately 55,000 (81%) cases occur in areas with well established or developing JE vaccination programmes, while approximately 12,900 (19%) occur in areas with minimal or no JE vaccination programmes. CONCLUSION: Recent data allowed us to refine the estimate of the global incidence of JE, which remains substantial despite improvements in vaccination coverage. More and better incidence studies in selected countries, particularly China and India, are needed to further refine these estimates. PMID- 22084518 TI - Impact of non-health policies on infant mortality through the social determinants pathway. PMID- 22084519 TI - Maternal death surveillance and response. PMID- 22084520 TI - Public health round-up. PMID- 22084521 TI - Family planning gains ground. AB - Once a taboo subject, family planning is increasingly being recognized as essential for social and economic development in countries in WHO's Eastern Mediterranean Region. Dale Gavlak reports from Jordan. PMID- 22084522 TI - Mixed uptake of social media among public health specialists. AB - Public health organizations are starting to use social media.Some specialists say they hold untapped potential for public health. Ben Jones reports. PMID- 22084523 TI - Will the Arab spring bring better health to Egyptians? AB - Parliamentary elections in Egypt this month look set to change the political landscape. Former member of parliament and equity campaigner Hoda Rashad tells Fiona Fleck why the country's public health programmes need to take a social justice approach. PMID- 22084524 TI - Twenty-year trends in the prevalence of disability in China. AB - OBJECTIVE: To evaluate changes in the age-adjusted prevalence of disability in transitional China from 1987 to 2006. METHODS: Data from nationally representative surveys conducted in 1987 and 2006 were used to calculate age adjusted disability prevalence rates by applying appropriate sample weights and directly adjusting to the age distribution of the 1990 Chinese population. Trends were assessed in terms of average annual percentage change. FINDINGS: The estimated number of disabled people in China in 1987 and 2006 was 52.7 and 84.6 million, respectively, corresponding to a weighted prevalence of 4.9% and 6.5%. The age-adjusted prevalence of disability decreased by an average of 0.5% per year (average annual percentage change, AAPC: -0.5%; 95% confidence interval, CI: -0.7 to -0.4) during 1987-2006. However, it increased by an average of 0.3% (AAPC: 0.3%; 95% CI: 0.1 to 0.5) per year in males and by an average of 1.0% (AAPC: 1.0%; 95% CI: 0.8 to 1.2) per year among rural residents, whereas among females it showed an average annual decrease of 1.5% (AAPC: -1.5%; 95% CI: -1.7 to -1.3) and among urban residents, an average annual decrease of 3.9% (AAPC: 3.9%; 95% CI: -4.3 to -3.5). Despite significant declining trends for hearing and speech, intellectual and visual disabilities, the annual age-adjusted prevalence of physical and mental disabilities increased by an average of 11.2% (AAPC: 11.2%; 95% CI: 10.5 to 11.9) and 13.3% (AAPC: 13.3%; 95% CI: 10.7 to 16.2), respectively. CONCLUSION: In China, the age-adjusted prevalence of disability has declined since 1987, with inconsistencies dependent on the type of disability. These findings call for continuing and specific efforts to prevent disabilities in China. PMID- 22084525 TI - Syphilis test availability and uptake at medical facilities in southern China. AB - OBJECTIVE: To examine syphilis testing capacity, screening coverage rates and types of syphilis tests used in medical facilities in southern China. METHODS: Eleven of the 14 municipalities in Guangdong province participated. Data on syphilis testing capacity, screening coverage and types of syphilis tests used were collected from all types of public medical facilities offering prenatal care (n = 109). A total of 494 680 women who delivered during 2004-2008 were studied. FINDINGS: In 2008, 54 196 pregnant women (43.1%) were not screened for syphilis. Among such women, 32 863 (60.6%) attended clinics without any syphilis testing capacity and 21 333 (39.4%) attended clinics that performed testing but were not screened. The likelihood of not having syphilis test capacity was much higher for hygiene stations (odds ratio, OR: 10; 95% confidence interval, CI: 4-25), services at the township level (OR: 33; 95% CI: 10-100) and services with <= 1000 deliveries per year (OR: 1.002; 95% CI: 1.001-1.003). These same service characteristics correlated with lower screening coverage rates (P < 0.01). Only one antenatal clinic had the capacity to conduct both treponemal and non treponemal tests for diagnosing syphilis. CONCLUSION: Syphilis screening is available in very few of the basic medical facilities offering prenatal care where most neonates in southern China are delivered. In light of this and of the increasing incidence of syphilis in the area, expanding point-of-care rapid syphilis testing is a priority. PMID- 22084526 TI - Under-registration of deaths in Thailand in 2005-2006: results of cross-matching data from two sources. AB - OBJECTIVE: To estimate the magnitude of under-registration of deaths, by age and sex, in Thailand. METHODS: THE DATA IN THIS STUDY WERE DERIVED FROM TWO SOURCES: the Thai Survey of Population Changes (SPC) 2005-2006, a consecutive multi-round household survey conducted over a 12-month period, and Thailand's vital registration records. SPC death entries for people of all ages were matched to 2005-2006 death records from vital registration. The principles of a dual records system were applied to estimate the magnitude of under-registration of deaths, classified by age and sex, using the Chandrasekaran-Deming formula. FINDINGS: Overall under-registration of deaths during 2005-2006 was 9.00% (95% confidence interval, CI: 8.95-9.05) for males and 8.36% (95% CI: 8.31-8.41) for females. For both males and females, under-registration decreased as age increased. Under registration was greatest among people of either sex aged 1-4 years, whereas it was < 10% among people 60 years of age and older, both males and females. CONCLUSION: These findings provided correction factors that can be used for adjusting mortality data from the registration system. PMID- 22084527 TI - Iodine status in late pregnancy and psychosocial determinants of iodized salt use in rural northern Viet Nam. AB - OBJECTIVE: To establish iodine status among pregnant women in rural northern Viet Nam and explore psychosocial predictors of the use of iodized salt in their households. METHODS: This prospective study included pregnant women registered in health stations in randomly-selected communes in Ha Nam province. At recruitment (< 20 weeks of gestation), sociodemographic factors, reproductive health, intimate partner relationship, family violence, symptoms of common mental disorders and use of micronutrient supplements were assessed. During a second assessment (> 28 weeks of gestation) a urine specimen was collected to measure urinary iodine concentration (UIC) and iodized salt use was assessed. Predictors were explored through univariable analyses and multivariable linear and logistic regression. FINDINGS: The 413 pregnant women who provided data for this study had a median UIC of 70 ug/l; nearly 83% had a UIC lower than the 150 ug/l recommended by the World Health Organization; only 73.6% reported using iodized salt in any form in their households. Iodized salt use was lower among nulliparous women (odds ratio, OR: 0.56; 95% confidence interval, CI: 0.32-0.96); less educated women (OR: 0.34; 95% CI: 0.16-0.71); factory workers or small-scale traders (OR: 0.52; 95% CI: 0.31-0.86), government workers (OR: 0.35; 95% CI: 0.13-0.89) and women with common mental disorders at recruitment (OR: 0.61; 95% CI: 0.38-0.98). CONCLUSION: The decline in the use of iodized salt in Viet Nam since the National Iodine Deficiency Disorders Control Programme was suspended in 2005 has placed pregnant women and their infants in rural areas at risk of iodine deficiency disorders. PMID- 22084528 TI - Human papillomavirus vaccine delivery strategies that achieved high coverage in low- and middle-income countries. AB - OBJECTIVE: To assess human papillomavirus (HPV) vaccination coverage after demonstration projects conducted in India, Peru, Uganda and Viet Nam by PATH and national governments and to explore the reasons for vaccine acceptance or refusal. METHODS: Vaccines were delivered through schools or health centres or in combination with other health interventions, and either monthly or through campaigns at fixed time points. Using a two-stage cluster sample design, the authors selected households in demonstration project areas and interviewed over 7000 parents or guardians of adolescent girls to assess coverage and acceptability. They defined full vaccination as the receipt of all three vaccine doses and used an open-ended question to explore acceptability. FINDINGS: Vaccination coverage in school-based programmes was 82.6% (95% confidence interval, CI: 79.3-85.6) in Peru, 88.9% (95% CI: 84.7-92.4) in 2009 in Uganda and 96.1% (95% CI: 93.0-97.8) in 2009 in Viet Nam. In India, a campaign approach achieved 77.2% (95% CI: 72.4-81.6) to 87.8% (95% CI: 84.3-91.3) coverage, whereas monthly delivery achieved 68.4% (95% CI: 63.4-73.4) to 83.3% (95% CI: 79.3-87.3) coverage. More than two thirds of respondents gave as reasons for accepting the HPV vaccine that: (i) it protects against cervical cancer; (ii) it prevents disease, or (iii) vaccines are good. Refusal was more often driven by programmatic considerations (e.g. school absenteeism) than by opposition to the vaccine. CONCLUSION: High coverage with HPV vaccine among young adolescent girls was achieved through various delivery strategies in the developing countries studied. Reinforcing positive motivators for vaccine acceptance is likely to facilitate uptake. PMID- 22084529 TI - Evaluating large-scale health programmes at a district level in resource-limited countries. AB - Recent experience in evaluating large-scale global health programmes has highlighted the need to consider contextual differences between sites implementing the same intervention. Traditional randomized controlled trials are ill-suited for this purpose, as they are designed to identify whether an intervention works, not how, when and why it works. In this paper we review several evaluation designs that attempt to account for contextual factors that contribute to intervention effectiveness. Using these designs as a base, we propose a set of principles that may help to capture information on context. Finally, we propose a tool, called a driver diagram, traditionally used in implementation that would allow evaluators to systematically monitor changing dynamics in project implementation and identify contextual variation across sites. We describe an implementation-related example from South Africa to underline the strengths of the tool. If used across multiple sites and multiple projects, the resulting driver diagrams could be pooled together to form a generalized theory for how, when and why a widely-used intervention works. Mechanisms similar to the driver diagram are urgently needed to complement existing evaluations of large-scale implementation efforts. PMID- 22084530 TI - Can pharmacogenomics improve malaria drug policy? AB - Coordinated global efforts to prevent and control malaria have been a tour-de force for public health, but success appears to have reached a plateau in many parts of the world. While this is a multifaceted problem, policy strategies have largely ignored genetic variations in humans as a factor that influences both selection and dosing of antimalarial drugs. This includes attempts to decrease toxicity, increase effectiveness and reduce the development of drug resistance, thereby lowering health care costs. We review the potential hurdles to developing and implementing pharmacogenetic-guided policies at a national or regional scale for the treatment of uncomplicated falciparum malaria. We also consider current knowledge on some component drugs of artemisinin combination therapies and ways to increase our understanding of host genetics, with the goal of guiding policy decisions for drug selection. PMID- 22084533 TI - Let us all join hands in strengthening the publication process. PMID- 22084531 TI - Redesigning the AIDS response for long-term impact. AB - Three decades since the human immunodeficiency virus (HIV) was identified, the pandemic of acquired immunodeficiency syndrome (AIDS) has developed into diverse epidemics around the world. In many populations, HIV infection has become endemic. While there is good progress on expanding access to treatment, with an estimated 6.6 million people on antiretroviral therapy at the end of 2010, prevention efforts are still highly inadequate with 2.6 million new infections occurring in 2009. Demand for treatment is increasing while funding is becoming more scarce and activism is waning. In 2007, the Joint United Nations Programme on HIV/AIDS (UNAIDS) established an independent forum called aids2031 to take a critical look at the global HIV/AIDS response. This paper outlines four key areas for a re-designed AIDS response based on the deliberations of this initiative and on the learning and experience of the first three decades of the epidemic: (i) a new culture of knowledge generation and utilization; (ii) transformed prevention and treatment to increase effectiveness; (iii) increased efficiency through better management and maximizing synergies with other programmes; and (iv) investment for the long term. Across all these areas is a strong emphasis on local capacity building, leadership, programme priorities and budgets. PMID- 22084534 TI - Traffic related air pollution and respiratory morbidity. PMID- 22084535 TI - Mapping of asthma research in India: A scientometric analysis of publications output during 1999-2008. AB - OBJECTIVE: This study analyzes the research output of India in asthma during the period from 1999 till 2008. It analyzes the growth, rank and global publications share, citation impact, share of international collaborative papers, contribution of major collaborative partner countries and contribution of various subject fields. It also analyzes the characteristics of most productive institutions, authors and high-cited papers. MATERIALS AND METHODS: SCOPUS database has been used to retrieve the data on publication output in asthma research. RESULTS: India ranks 15(th) position among the top 23 countries in asthma research, with its global publication share of 1.27% (862 papers), registering an average citation per paper of 3.43 and achieved an h-index of 33 during 1999-2008. CONCLUSION: Indian research output on asthma is quite low in the global context as reflected from its publication output per thousand population (0.001) and its world publication share (1.27%) during 1999-2008. Also, the impact and quality of Indian research is low compared to select developed and developing countries. PMID- 22084536 TI - Normative values for maximal respiratory pressures in an Indian Mangalore population: A cross-sectional pilot study. AB - OBJECTIVE: The objective of the pilot study is to obtain normal maximal inspiratory and expiratory pressures for individuals in the age group 20-70 years in the Mangalore population and to predict normal values according to age, sex, height, and weight using the regression equation. MATERIALS AND METHODS: Two hundred and fifty subjects were selected through a convenient method of sampling. Fifty subjects each were enrolled in the following age groups: 20 to 29, 30 to 39, 40 to 49, 50 to 59, and 60 to 70. Each group had 50 subjects (males-25 and females-25). Baseline data such as height, weight, body mass index were recorded. Maximal inspiratory pressure (PI) and expiratory pressure (PE) were determined following standardized protocol. RESULT: With regard to PI max and PE max, the measured values were significantly lower than those recorded in previous studies for both males (30%) and females (20%). We found that age served as the best factor for the prediction of PI max and PE max in both genders. CONCLUSION: The results of this study can be used to predict respiratory muscle strength in healthy adult subjects, and the strategy employed in this study will serve as a useful, simple, reproducible, rapid assessment of respiratory muscle function and also aid the planning of treatment. PMID- 22084537 TI - Respiratory effects of air pollutants among nonsmoking traffic policemen of Patiala, India. AB - BACKGROUND: Air pollution due to road traffic is a serious health hazard and thus the persons who are continuously exposed, may be at an increased risk. Although several studies have confirmed the ill effects of air pollutants on the lung function of traffic policemen, only a few have investigated the relationship between respiratory health and duration of exposure in this category of occupationally exposed persons. AIM: The study was carried out with the aim of evaluating the extent of impairment in lung function in traffic policemen in respect to an unexposed control group having the same age group. MATERIALS AND METHODS: A cross-sectional study was conducted in which the spirometric parameters of a group of 100 nonsmoking traffic policemen, aged 20-55 years, working in and around Patiala city, were compared with those obtained in an age matched control group, consisting of 100 healthy males, serving in the Punjab Police, who have never done traffic duty and are thus not exposed to traffic pollution. Lung function was done with MEDSPIROR. The data on the overall health status of the subjects was collected using the standard Respirator Medical Evaluation Questionnaire. The statistical analysis was carried out with SPSS PC software version 13. RESULTS: Traffic policemen recorded a significant decline in various parameters, such as forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), and peak expiratory flow rate (PEFR) when compared with controls, and is probably due to exposure to vehicular pollution. It was also observed that in traffic policemen with >8 years of exposure, the values of FVC (2.7 L), FEV(1) (1.8 L), and PEFR (7.5 L/s) were significantly lower than those obtained in traffic policemen with <8 years of exposure, in whom the values were 2.9 L, 2.3 L, and 7.7 L/s for FVC, FEV(1), and PEFR, respectively. CONCLUSION: The effect of pollution by vehicular exhausts may be responsible for these pulmonary function impairments. PMID- 22084538 TI - Chronic obstructive pulmonary disease: Does gender really matter? AB - BACKGROUND: Limited data is available on the clinical expression of chronic obstructive pulmonary disease (COPD) from India. The impact of gender on expression of COPD has received even less attention. Apart from tobacco smoke, indoor air pollution, especially from biomass fuel may play an important role in development of COPD in women. MATERIALS AND METHODS: Seven hundred and two patients of COPD were studied regarding the etiological and risk factors leading to COPD, gender-related differences in clinical presentation, radiological expression of COPD and the co-morbidities in COPD. RESULTS: Tobacco smoke in the form of beedi smoking was the predominant smoke exposure in males, whereas smoke from biofuel burning was the predominant exposure in females. As compared to males, females were younger, reported more dyspnea, more severe bronchial obstruction, more exacerbations, and exhibited higher prevalence of systemic features. Also, females smoked less and had lesser incidence of productive cough, lower body mass index, lesser co-morbidities and less number of hospital admissions as compared to males. Males were more likely than females to have an emphysema-predominant phenotype, while airway-predominant disease was more common among females. CONCLUSION: The current study shows that gender-related differences do exist in COPD patients. Understanding these differences in etiological agent and clinical picture will help early diagnosis of COPD in females. PMID- 22084539 TI - Manifestations of tuberculosis in HIV/AIDS patients and its relationship with CD4 count. AB - BACKGROUND: HIV/AIDS pandemic is responsible for the resurgence of TB worldwide, resulting in increased morbidity and mortality. HIV and Mycobacterium tuberculosis have a synergistic interaction; each propagates progression of the other. Coinfection with HIV infection leads to difficulties in both the diagnosis and treatment of tuberculosis, increase risk of death, treatment failure and relapse. OBJECTIVE: The aim of the present study is to study the clinical, radiological profile of pulmonary and extrapulmonary tuberculosis (EPTB) in HIV seropositive patients and their relationship to CD4 counts. MATERIALS AND METHODS: It was a prospective study conducted over a period of 1 year in the department of medicine, Indira Gandhi Medical College, Shimla. We examined 87 HIV infected patients with associated tuberculosis recruited from the department of medicine and antiretroviral center and were subjected to thorough clinical examination, X-ray chest, tuberculin testing and sputum examination for AFB and necessary relevant investigations for EPTB. RESULTS: Most common affected age group was 31-40 years. EPTB is the commonest form of TB in our study detected in 65 patients. Commonest EPTB was CNS tuberculosis. Disseminated tuberculosis was only found in patient with CD4 count less than 200/cmm. Majority of lymph node TB was diagnosed by fine needle aspiration cytology (FNAC) examination. All patients with AFB-positive lymph node had CD4 count below 200/cum. CONCLUSIONS: The results of this study provide information regarding the various forms of TB and their presentation in HIV-infected persons. Early diagnosis of tuberculosis and prompt institution of antitubercular treatment (ATT) reduces mortality and morbidity significantly. In resource-poor areas, the diagnosis can be established with cytological/biochemical analysis of fluid, histopathological examination and ZN staining of tissue coupled with radiological features and response to ATT. Therefore, adequate knowledge of the manifestations of tuberculosis in HIV infected patients is absolutely necessary for optimal management and to reduce mortality and morbidity. PMID- 22084540 TI - Clinical characteristics and treatment outcomes in 132 patients with malignant mesothelioma. AB - PURPOSE: Our objective is to scrutinize clinical, laboratory, radiological characteristics, treatment regimens, and treatment outcomes of malignant mesothelioma (MM) cases in our hospital. MATERIALS AND METHODS: We investigated, retrospectively, the clinical characteristics and treatment outcomes of all 132 MM patients at Dicle University Hospital between January 2006 and April 2010. RESULTS: A total of 82 (62.1%) patients were male, and 50 (37.9%) female. Median age was 56.0 years. Mean survival time was 9.6+/-6.9 months. Mean survival time of patients who had received best supportive care was 7.5 months, chemotherapy 10.4 months, and multimodality treatment regimen 12.6 months. Patients in the multimodality treatment group survived longer than did those in the other two groups (P=0.042). A total of 76 patients received chemotherapy, of whom 17 (22.3%) were administered Cisplatin/Carboplatin and Gemcitabine, 58 (76.4%) Cisplatin/Carboplatin and Pemetrexed, and one (1.3%) Cisplatin + Docetaxel. Complete and partial response to treatment in patients receiving Cisplatin/Carboplatin and Gemcitabine was found 47.1% and Cisplatin/Carboplatin and Pemetrexed was found 50.0% (P>0.05). CONCLUSIONS: MM related to asbestos exposure is seen frequently in Turkey. Patients present with the typical clinical features of dyspnea, weight loss, and chest pain. Survival analysis shows that patients receiving multimodality treatment may be better. PMID- 22084541 TI - Impact of inhalation therapy on oral health. AB - Inhalation therapy has been employed as the mainstay of the treatment in chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Beta-2 agonists, anticholinergic bronchodilators, inhaled corticosteroids, and sodium cromoglycate are often used alone or in combination in an inhaled form. Studies have shown that inhaled drugs used in the treatment have some adverse effects on the oral health based on their dosage, frequency, and duration of use. Several oral conditions such as xerostomia, dental caries, candidiasis, ulceration, gingivitis, periodontitis, and taste changes have been associated with inhalation therapy. Since the prevalence of chronic respiratory diseases is rising, it is important to provide optimal oral care to the individuals receiving inhalation therapy. This article will review the influence of inhaled drugs on the oral health of individuals and adequate management and prevention of the same. PMID- 22084542 TI - Pulmonary rehabilitation: An overview. AB - The burden of chronic obstructive pulmonary disease (COPD) has increased recently in developing countries. On the other hand, structured or non-structured rehabilitation services for COPD patients are not routinely available in these countries. We, therefore, planned this review to re-emphasize the emerging benefits of pulmonary rehabilitation in COPD population. Aim of this review is to stimulate pulmonary physicians in India and other resource-poor areas of the world so that they start using pulmonary rehabilitation or its components more often. The search included standard english literature PubMed citation of relevant original articles, review articles and practice guidelines. The articles and reviews were searched including standard MeSH terms - Rehabilitation (TIAB) and pulmonary disease, chronic obstructive/therapy (MAJOR) and guidelines (TIAB). Available 58 articles in English including 23 reviews from July 2001 to October 2010 were screened for evidence-based benefits regarding respiratory rehabilitation as a whole or its different components. The cross references and current citations relating to primary articles were also included for description. No attempt was done to make a systematic analysis because our purpose was not to derive evidence-based recommendations from database and because sufficient evidence is already available for benefits of selected components of pulmonary rehabilitation in COPD patients. Pulmonary rehabilitation has emerged as an important modality as an adjunct to other therapies in patients of COPD. Limited and more cost-effective protocols are to be developed and executed by healthcare providers, especially in developing countries like India. PMID- 22084543 TI - Hughes-Stovin syndrome: A rare cause of hemoptysis. AB - Multiple pulmonary artery aneurysms are seen along with venous thrombosis in Hughes-Stovin syndrome, which many investigators believe is an incomplete form of Behcet's disease. We present a case of hemoptysis with multiple pulmonary artery aneurysms, femoral vein thrombosis, and oral ulcers with emphasis on its CT features. PMID- 22084544 TI - A rapidly developing lung mass diagnosed as desmoplastic small round cell tumor. AB - We present a case of a young male who presented with complaints of fever along with cough and sputum. He was diagnosed with having right pleural effusion. He was already taking anti-tubercular therapy for one month before presentation. He was started on intravenous antibiotics and continued on anti-tubercular therapy in our hospital, based on his high leukocyte count, pleural fluid analysis, and ultrasonographic report of multiple hypoechoic areas in the liver. His symptoms continued to worsen and he subsequently developed mediastinal widening and a left lung mass. Commuted tomography (CT)-guided biopsy of the lung mass revealed a desmoplastic small-round-cell tumor. Desmoplastic small-round-cell tumor is a rare and aggressive tumor, which presents rarely as a mediastinal and lung mass. This tumor has very poor prognosis. PMID- 22084545 TI - Subcutaneous emphysema due to bronchial foreign body demonstrated by multidetector-row computed tomography. AB - Foreign body aspiration is an important cause of emergency hospital admissions in young children less than 3 years of age. It may manifest with acute respiratory difficulty, choking and wheeze acutely or may be asymptomatic. Surgical emphysema is an unusual presentation of bronchial foreign body aspiration in young children. We describe an infant with bronchial foreign body aspiration that manifested with subcutaneous emphysema and pneumomediastinum. Multidetector-row CT with virtual bronchoscopy helped in the diagnosis by detecting and localizing the intraluminal foreign body in the right main bronchus that was removed with rigid bronchoscopy. PMID- 22084546 TI - Cement dust exposure-related emphysema in a construction worker. AB - Although, smoking is considered the most important predisposing factor in development of emphysema; environmental exposures also play an important role. There have been several studies on work related respiratory symptoms and ventilatory disorders among employees of cement industry. We report a case of cement exposure related emphysema in 75 years old woman construction worker. PMID- 22084547 TI - Herniation of unruptured tuberculous lung abscess into chest wall without pleural or bronchial spillage. AB - A 22-year-old unmarried man presented to the chest outpatient department with a history of productive cough of two-month duration. He also complained of pain and swelling on the anterior aspect of right side of chest of one-month duration. Imaging studies of the thorax, including chest roentgenography and computerized tomography, revealed an unruptured lung abscess which had herniated into the chest wall. Culture of pus aspirated from the chest wall swelling grew Mycobacterium tuberculosis. He was diagnosed to have a tuberculous lung abscess which had extended into the chest wall, without spillage into the pleural cavity or the bronchial tree. Antituberculosis drugs were prescribed, and he responded to the treatment with complete resolution of the lesion. PMID- 22084548 TI - Spontaneous esophageal-pleural fistula. AB - Spontaneous esophageal-pleural fistula (EPF) is a rare entity. We describe a case in a middle-aged female who presented with severe retrosternal chest pain and shortness of breadth. Chest computed tomography showed right EPF and hydropneumothorax. She was managed conservatively keeping the chest tube drainage and performing feeding jejunostomy. A brief review of the imaging finding and management of EPF is discussed. PMID- 22084549 TI - Traumatic esophago-bronchopleural fistula-CT finding and treatment using glue: A procedure not so commonly performed. AB - Bronchopleural fistulas can occur from a number of causes (infective, traumatic, or neoplastic). Combined esophageal-pleural and bronchopleural fistula is not a common entity and previously has been reported after pneumonectomy. We describe the imaging findings and procedure of endoscopic glue injection in a case of combined esophageal-pleural and bronchopleural fistula after penetrating thoracic trauma. The treatment included esophageal exclusion for esophageal-pleural fistula, followed by endoscopic injection of glue for closure of bronchopleural fistula. The fistulae were completely sealed. PMID- 22084550 TI - Right hilar mass with hemoptysis: An unusual presentation of uncommon disorder. AB - Common differential diagnosis of lung and hilar opacity includes infectious pathology or a mitotic lesion. Behcet's disease (BD) is a rarely diagnosed disease in Indian subcontinent. BD is a multisystem inflammatory disorder that presents with recurrent orogenital ulceration, uveitis, and erythema nodosum. We present here the case of a patient who presented with recurrent hemoptysis with radiological picture of hilar mass, during the evaluation of which the diagnosis of BD was established. PMID- 22084552 TI - Two cases of aspiration of calcium tablets. AB - Two clinical cases of aspiration are reported in elderly ladies with differing presentations following inhalation of the same brand of calcium tablet. One of the patients distinctly recalled the choking episode, whereas the other failed to do so making the diagnosis of aspiration difficult. One of the aspirated tablets was successfully retrieved during rigid bronchoscopy after the patient reported several months of cough requiring multiple courses of antibiotics. The other aspirated tablet was coughed up by the patient after the successful treatment of a pneumonia complicated by a parapneumonic effusion. PMID- 22084551 TI - Solitary plasmacytoma of the rib: A rare case. AB - Localized solitary plasmacytoma of the bone is a rare disease and is characterized by only one or two isolated bone lesions with no evidence of disease dissemination. We report a case of solitary plasmacytoma of the rib in a 43-year-old female. The patient underwent complete en-bloc resection of the chest wall including rib, muscle, and parietal pleura. Patient is asymptomatic without any recurrence after two and half years of follow up. PMID- 22084553 TI - Hydatidothorax. PMID- 22084554 TI - Hemoptysis with a classical radiological sign. AB - There can be various causes for hemoptysis. We present here a case of hemoptysis in which the chest X-ray helped us to arrive at the diagnosis because of a classical sign. This highlights the need of identifying this finding for prompt recognition of the cause of hemoptysis. PMID- 22084555 TI - Habits of tobacco use among the medical and non-medical students of Kolkata. PMID- 22084556 TI - A study on habits of tobacco use among medical and non-medical students of Kolkata. PMID- 22084557 TI - Mycobacteria in keloid. PMID- 22084558 TI - Closed needle pleural biopsy: A victim of western advancement? PMID- 22084559 TI - Percutaneous closed-needle pleural biopsy and undiagnosed exudative pleural effusion. PMID- 22084560 TI - Pneumothorax in hair dye poisoning: An unrecognized danger. PMID- 22084561 TI - Publication: An essential step in research. PMID- 22084562 TI - Characterization and inference of gene gain/loss along burkholderia evolutionary history. AB - A comparative analysis of 60 complete Burkholderia genomes was conducted to obtain insight in the evolutionary history behind the diversity and pathogenicity at species level. A concatenated multiprotein phyletic pattern and a dataset with Burkholderia clusters of orthologous genes (BuCOGs) were constructed. The extent of horizontal gene transfer (HGT) was assessed using a Markov based probabilistic method. A reconstruction of the gene gains and losses history shows that more than half of the Burkholderia genes families are inferred to have experienced HGT at least once during their evolution. Further analysis revealed that the number of gene gain and loss was correlated with the branch length. Genomic islands (GEIs) analysis based on evolutionary history reconstruction not only revealed that most genes in ancient GEIs were gained but also suggested that the fraction of the genome located in GEIs in the small chromosomes is higher than in the large chromosomes in Burkholderia. The mapping of coexpressed genes onto biological pathway schemes revealed that pathogenicity of Burkholderia strains is probably mainly determined by the gained genes in its ancestor. Taken together, our results strongly support that gene gain and loss especially in ancient evolutionary history play an important role in strain divergence, pathogenicity determinants of Burkholderia and GEIs formation. PMID- 22084563 TI - On the Interplay between the Evolvability and Network Robustness in an Evolutionary Biological Network: A Systems Biology Approach. AB - In the evolutionary process, the random transmission and mutation of genes provide biological diversities for natural selection. In order to preserve functional phenotypes between generations, gene networks need to evolve robustly under the influence of random perturbations. Therefore, the robustness of the phenotype, in the evolutionary process, exerts a selection force on gene networks to keep network functions. However, gene networks need to adjust, by variations in genetic content, to generate phenotypes for new challenges in the network's evolution, ie, the evolvability. Hence, there should be some interplay between the evolvability and network robustness in evolutionary gene networks. In this study, the interplay between the evolvability and network robustness of a gene network and a biochemical network is discussed from a nonlinear stochastic system point of view. It was found that if the genetic robustness plus environmental robustness is less than the network robustness, the phenotype of the biological network is robust in evolution. The tradeoff between the genetic robustness and environmental robustness in evolution is discussed from the stochastic stability robustness and sensitivity of the nonlinear stochastic biological network, which may be relevant to the statistical tradeoff between bias and variance, the so called bias/variance dilemma. Further, the tradeoff could be considered as an antagonistic pleiotropic action of a gene network and discussed from the systems biology perspective. PMID- 22084564 TI - Mathematical prognostic biomarker models for treatment response and survival in epithelial ovarian cancer. AB - Following initial standard chemotherapy (platinum/taxol), more than 75% of those patients with advanced stage epithelial ovarian cancer (EOC) experience a recurrence. There are currently no accurate prognostic tests that, at the time of the diagnosis/surgery, can identify those patients with advanced stage EOC who will respond to chemotherapy. Using a novel mathematical theory, we have developed three prognostic biomarker models (complex mathematical functions) that based on a global gene expression analysis of tumor tissue collected during surgery and prior to the commencement of chemotherapy-can identify with a high accuracy those patients with advanced stage EOC who will respond to the standard chemotherapy [long-term survivors (>7 yrs)] and those who will not do so [short term survivors (<3 yrs)]. Our three prognostic biomarker models were developed with 34 subjects and validated with 20 unknown (new and different) subjects. Both the overall biomarker model sensitivity and specificity ranged from 95.83% to 100.00%. The 12 most significant genes identified, which are also the input variables to the three mathematical functions, constitute three distinct gene networks with the following functions: 1) production of cytoskeletal components, 2) cell proliferation, and 3) cell energy production. The first gene network is directly associated with the mechanism of action of anti-tubulin chemotherapeutic agents, such as taxanes and epothilones. This could have a significant impact in the discovery of new, more effective pharmacological treatments that may significantly extend the survival of patients with advanced stage EOC. PMID- 22084565 TI - Improved Statistical Analysis for Array CGH-Based DNA Copy Number Aberrations. AB - Array-based comparative genomic hybridization (aCGH) allows measuring DNA copy number at the whole genome scale. In cancer studies, one may be interested in identifying DNA copy number aberrations (CNAs) associated with certain clinicopathological characteristics such as cancer metastasis. We proposed to define test regions based on copy number pattern profiles across multiple samples, using either smoothed log(2)-ratio or discrete data of copy number gain/loss calls. Association test performed on the refined test regions instead of the probes has improved power due to reduced number of tests. We also compared three types of measurement of copy number levels, normalized log(2)-ratio, smoothed log(2)-ratio, and copy number gain or loss calls in statistical hypothesis testing. The relative strengths and weaknesses of the proposed method were demonstrated using both simulation studies and real data analysis of a liver cancer study. PMID- 22084567 TI - Erratum for "Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide". AB - [This corrects the article on p. 7 in vol. 6, PMID: 21461292.]. PMID- 22084566 TI - New short term prediction method for chemical carcinogenicity by hepatic transcript profiling following 28-day toxicity tests in rats. AB - We have previously shown the hepatic gene expression profiles of carcinogens in 28-day toxicity tests were clustered into three major groups (Group-1 to 3). Here, we developed a new prediction method for Group-1 carcinogens which consist mainly of genotoxic rat hepatocarcinogens. The prediction formula was generated by a support vector machine using 5 selected genes as the predictive genes and predictive score was introduced to judge carcinogenicity. It correctly predicted the carcinogenicity of all 17 Group-1 chemicals and 22 of 24 non-carcinogens regardless of genotoxicity. In the dose-response study, the prediction score was altered from negative to positive as the dose increased, indicating that the characteristic gene expression profile emerged over a range of carcinogen specific doses. We conclude that the prediction formula can quantitatively predict the carcinogenicity of Group-1 carcinogens. The same method may be applied to other groups of carcinogens to build a total system for prediction of carcinogenicity. PMID- 22084568 TI - Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice. AB - AIM: Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA) developed to measure a specific MMP12-derived fragment of mimecan, MMCN-151, in apolipoprotein-E knockout (ApoE-KO) mice. METHODS AND RESULTS: A mouse monoclonal antibody raised against MMCN-151 was used to develop a competitive ELISA. The assay was validated using samples from 20 ApoE-KO and 20 wild type [C57 BL/6] male mice fed a normal or high-fat diet (HFD) for up to 20 weeks. The technical reliability of the assay was established with intra-assay variability <2% and inter-assay variability <10%. The lowest limit of quantification of MMCN-151 was 0.5 ng/ml. ApoE-KO mice fed a HFD for 20 weeks had four-fold increased circulating levels of MMCN-151 compared to baseline, whereas MMCN-151 levels in control mice on HFD increased two-fold compared with baseline. After 10 weeks of a HFD, a significant difference in MMCN-151 levels was observed between ApoE-KO and control mice (P = 0.005) and became more significant at 20 weeks (P = 0.002). CONCLUSIONS: The newly developed assay is a reliable detector of MMCN-151 levels which ultimately may be useful indicators of arterial remodeling in patients affected by atherosclerotic disease. PMID- 22084569 TI - The primary cilium as a biomarker in the hypoxic adaptation of bone marrow derived mesenchymal stromal cells: a role for the secreted frizzled-related proteins. AB - A pivotal role in guiding mesenchymal stem cell (MSC) differentiation has recently been attributed to the primary cilium. This solitary, non-motile microtubule-based organelle emerging from the cell surface acts as a sensorial membrane structure reflecting developmental and adaptive processes associated with pathologies including human cystic kidney disease, skeletal malformations, obesity and cancer. Given that the intrinsic hypoxic adaptation of MSC remains poorly understood within ischemic tissues or hypoxic tumours, we questioned whether the hypoxia inducible factor-1alpha (HIF-1alpha) might be a downstream effector regulating cilium maintenance. We show that murine bone marrow-derived MSC cultured under hypoxic conditions (1.2% O(2)) lose their primary cilia in a time-dependent manner. Gene silencing of HIF-1alpha prevented cilia loss in hypoxic cultures, and generation of MSC expressing a constitutively active HIF 1alpha (MSC-HIF) was found to decrease primary cilium formation. A Wnt pathway related gene expression array was also performed on MSC-HIF and indicated that the secreted Frizzled-related proteins (sFRP)-1, -3 and -4 were down-regulated, while sFRP-2 was up-regulated. Overexpression of recombinant sFRP-2 or gene silencing of sFRP-1, -3 and -4 in MSC led to primary cilium disruption. These results indicate a molecular signalling mechanism for the hypoxic disruption of the primary cilium in MSC involving an HIF-1alpha/sFRP axis. This mechanism contributes to our understanding of the adaptive processes possibly involved in the oncogenic transformation and tumour-supporting potential of MSC. Our current observations also open up the possibility for the primary cilia to serve as a biomarker in MSC adaptation to low oxygen tension within (patho)physiological microenvironments. PMID- 22084570 TI - Detection of suPAR in the Saliva of Healthy Young Adults: Comparison with Plasma Levels. AB - The soluble urokinase plasminogen activator receptor (suPAR) has been detected in blood, plasma, serum, urine, ovarian cystic fluid, and cerebrospinal fluid. Elevated suPAR levels in plasma have been associated with negative outcomes in various diseases, such as bacteremia, sepsis, SIRS, cardiovascular disease, cancer, and tuberculosis. The primary aim of this study was to investigate whether suPAR can be detected in saliva from healthy individuals and thus, if saliva suPAR can be related to plasma suPAR, CRP, BMI, or gender. Blood and unstimulated whole saliva was collected from 20 healthy individuals (10 female and 10 male, median age of 28 years; range 21-41). CRP and suPAR were measured with ELISA in saliva and serum/plasma. suPAR was detected in all saliva samples in the 5.2-28.1 ng/mL range, with a median value of 17.1 ng/mL. Saliva suPAR was significantly higher (P < 0.001) but not correlated to plasma suPAR in healthy young adults with normal plasma suPAR levels. suPAR and CRP levels were correlated in blood but not in saliva. No correlation was found between BMI, age, or gender and suPAR in saliva. PMID- 22084571 TI - Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni. AB - The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts. PMID- 22084572 TI - Functional Annotation Analytics of Rhodopseudomonas palustris Genomes. AB - Rhodopseudomonas palustris, a nonsulphur purple photosynthetic bacteria, has been extensively investigated for its metabolic versatility including ability to produce hydrogen gas from sunlight and biomass. The availability of the finished genome sequences of six R. palustris strains (BisA53, BisB18, BisB5, CGA009, HaA2 and TIE-1) combined with online bioinformatics software for integrated analysis presents new opportunities to determine the genomic basis of metabolic versatility and ecological lifestyles of the bacteria species. The purpose of this investigation was to compare the functional annotations available for multiple R. palustris genomes to identify annotations that can be further investigated for strain-specific or uniquely shared phenotypic characteristics. A total of 2,355 protein family Pfam domain annotations were clustered based on presence or absence in the six genomes. The clustering process identified groups of functional annotations including those that could be verified as strain specific or uniquely shared phenotypes. For example, genes encoding water/glycerol transport were present in the genome sequences of strains CGA009 and BisB5, but absent in strains BisA53, BisB18, HaA2 and TIE-1. Protein structural homology modeling predicted that the two orthologous 240 aa R. palustris aquaporins have water-specific transport function. Based on observations in other microbes, the presence of aquaporin in R. palustris strains may improve freeze tolerance in natural conditions of rapid freezing such as nitrogen fixation at low temperatures where access to liquid water is a limiting factor for nitrogenase activation. In the case of adaptive loss of aquaporin genes, strains may be better adapted to survive in conditions of high-sugar content such as fermentation of biomass for biohydrogen production. Finally, web based resources were developed to allow for interactive, user-defined selection of the relationship between protein family annotations and the R. palustris genomes. PMID- 22084573 TI - In Vitro Enhanced Sensitivity to Cisplatin in D67Y BRCA1 RING Domain Protein. AB - BRCA1 is a tumor suppressor protein involved in maintaining genomic integrity through multiple functions in DNA damage repair, transcriptional regulation, cell cycle checkpoint, and protein ubiquitination. The BRCA1-BARD1 RING complex has an E3 ubiquitin ligase function that plays essential roles in response to DNA damage repair. BRCA1-associated cancers have been shown to confer a hypersensitivity to chemotherapeutic agents. Here, we have studied the functional consequence of the in vitro E3 ubiquitin ligase activity and cisplatin sensitivity of the missense mutation D67Y BRCA1 RING domain. The D67Y BRCA1 RING domain protein exhibited the reduced ubiquitination function, and was more susceptible to the drug than the D67E or wild-type BRCA1 RING domain protein. This evidence emphasized the potential of using the BRCA1 dysfunction as an important determinant of chemotherapy responses in breast cancer. PMID- 22084575 TI - Economic aspects of sanitation in developing countries. AB - BACKGROUND: Improved sanitation has been shown to have great impacts on people's health and economy. However, the progress of achieving the Millennium Development Goals (MDGs) on halving the proportion of people without access to clean water and basic sanitation by 2015 has thus far been delayed. One of the reasons for the slow progress is that policy makers, as well as the general public, have not fully understood the importance of the improved sanitation solutions. This paper, by gathering relevant research findings, aims to report and discuss currently available evidence on the economic aspects of sanitation, including the economic impacts of unimproved sanitation and the costs and economic benefits of some common improved sanitation options in developing countries. METHODS: DATA USED IN THIS PAPER WERE OBTAINED FROM DIFFERENT INFORMATION SOURCES: international and national journal articles and reports, web-based statistics, and fact sheets. We used both online search and hand search methods to gather the information. RESULTS: Scientific evidence has demonstrated that the economic cost associated with poor sanitation is substantial. At the global level, failure to meet the MDG water and sanitation target would have ramifications in the area of US$38 billion, and sanitation accounts for 92% of this amount. In developing countries, the spending required to provide new coverage to meet the MDG sanitation target (not including program costs) is US$142 billion (US$ year 2005). This translates to a per capita spending of US$28 for sanitation. Annually, this translates to roughly US$14 million. The evidence complied in this paper demonstrates that investing in sanitation is socially and economically worthwhile. For every US$1 invested, achieving the sanitation MDG target and universal sanitation access in the non-OECD countries would result in a global return of US$9.1 and US$11.2, respectively. CONCLUSION: Given the current state of knowledge, sanitation is undeniably a profitable investment. It is clear that achieving the MDG sanitation target not only saves lives but also provides a foundation for economic growth. PMID- 22084574 TI - Exemestane in the adjuvant treatment of breast cancer in postmenopausal women. AB - Exemestane is an irreversible inhibitor of the aromatase enzyme, which is a key component in the production of estrogen. The majority of breast cancers are sensitive to the proliferative effects of estrogen. Exemestane is approved for the adjuvant treatment of postmenopausal women with breast cancer after 2 to 3 years of tamoxifen therapy, based on a 32% improvement in disease-free survival compared with 5 years of tamoxifen alone (P < 0.001). Exemestane has also shown clinical benefits as an upfront therapy. The safety profile of exemestane shares some side effects with tamoxifen (hot flashes and arthralgia), but is not associated with an increased risk of endometrial cancer or thromboembolic events. This review will discuss in detail the efficacy and safety of exemestane in early breast cancer. PMID- 22084576 TI - Introductory editorial. PMID- 22084577 TI - Tryptophan research in panic disorder. AB - A considerable body of evidence suggests the involvement of serotonin neurotransmission in the pathogenesis of panic disorder. Research on pathways and functions of tryptophan, an essential amino acid converted into serotonin, may advance our understanding of serotonergic actions in panic disorder and related phenomena. The investigative approaches in this field include manipulations of tryptophan availability as well as genetic association and functional brain imaging studies. In this review we examine the principle findings of these studies and propose further research directions. PMID- 22084579 TI - Paolo guidetti. PMID- 22084578 TI - Kynurenine pathway metabolites in humans: disease and healthy States. AB - Tryptophan is an essential amino acid that can be metabolised through different pathways, a major route being the kynurenine pathway. The first enzyme of the pathway, indoleamine-2,3-dioxygenase, is strongly stimulated by inflammatory molecules, particularly interferon gamma. Thus, the kynurenine pathway is often systematically up-regulated when the immune response is activated. The biological significance is that 1) the depletion of tryptophan and generation of kynurenines play a key modulatory role in the immune response; and 2) some of the kynurenines, such as quinolinic acid, 3-hydroxykynurenine and kynurenic acid, are neuroactive. The kynurenine pathway has been demonstrated to be involved in many diseases and disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, AIDS dementia complex, malaria, cancer, depression and schizophrenia, where imbalances in tryptophan and kynurenines have been found. This review compiles most of these studies and provides an overview of how the kynurenine pathway might be contributing to disease development, and the concentrations of tryptophan and kynurenines in the serum, cerebrospinal fluid and brain tissues in control and patient subjects. PMID- 22084581 TI - Production and Peripheral Roles of 5-HTP, a Precursor of Serotonin. AB - Serotonin (5-hydroxytryptamine [5-HT]) has been implicated in a variety of physiological and pathological functions. Multiple steps of enzyme reactions enable biosynthesis of 5-HT. The first and rate-limiting step of the reaction is the synthesis of 5-hydroxy-L-tryptophan (5-HTP) from L-tryptophan. This step is dictated by an enzyme, tryptophan hydroxylase (TPH). TPH requires 6R-L-erythro 5,6,7,8-tetrahydrobiopterin (BH4) as a co-substrate of TPH. 5-HTP has been simply regarded as a precursor of 5-HT and it is believed that the biological significance of 5-HTP is essentially ascribed to the production of 5-HT. However, recent works shed light on the specific functions of 5-HTP in the periphery. In this review article, we focus on the specific roles of exogenous 5-HTP as well as the endogenous 5-HTP in the gut epithelial cells. Since systemic treatment with 5 HTP is applied to patients with lower 5-HT levels, the studies on the specific role of 5-HTP might create an opportunity to explore the effects of exogenously applied 5-HTP in the gut in man. PMID- 22084580 TI - Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-wake Cycle and Immune Function: Streptopelia Risoria as a Model. AB - In the present review we summarize the relationship between the amino acid, tryptophan, the neurotransmitter, serotonin, and the indole, melatonin, with the rhythms of sleep/wake and the immune response along with the possible connections between the alterations in these rhythms due to aging and the so-called "serotonin and melatonin deficiency state." The decrease associated with aging of the brain and circulating levels of serotonin and melatonin seemingly contributes to the alterations of both the sleep/wake cycle and the immune response that typically accompany old age. The supplemental administration of tryptophan, e.g. the inclusion of tryptophan-enriched food in the diet, might help to remediate these age-related alterations due to its capacity of raise the serotonin and melatonin levels in the brain and blood. Herein, we also summarize a set of studies related to the potential role that tryptophan, and its derived product melatonin, may play in the restoration of the aged circadian rhythms of sleep/wake and immune response, taking the ringdove (Streptopeliarisoria) as a suitable model. PMID- 22084582 TI - Effects of Kynurenine Pathway Metabolites on Intracellular NAD Synthesis and Cell Death in Human Primary Astrocytes and Neurons. AB - The kynurenine pathway (KP) is a major route of L-tryptophan catabolism resulting in the production of the essential pyridine nucleotide nicotinamide adenine dinucleotide, (NAD(+)). Up-regulation of the KP during inflammation leads to the release of a number of biologically active metabolites into the brain. We hypothesised that while some of the extracellular KP metabolites may be beneficial for intracellular NAD(+) synthesis and cell survival at physiological concentrations, they may contribute to neuronal and astroglial dysfunction and cell death at pathophysiological concentrations. In this study, we found that treatment of human primary neurons and astrocytes with 3-hydroxyanthranilic acid (3-HAA), 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), and picolinic acid (PIC) at concentrations below 100 nM significantly increased intracellular NAD(+) levels compared to non-treated cells. However, a dose dependent decrease in intracellular NAD(+) levels and increased extracellular LDH activity was observed in human astrocytes and neurons treated with 3-HAA, 3-HK, QUIN and PIC at concentrations >100 nM and kynurenine (KYN), at concentrations above 1 MUM. Intracellular NAD(+) levels were unchanged in the presence of the neuroprotectant, kynurenic acid (KYNA), and a dose dependent increase in intracellular NAD(+) levels was observed for TRP up to 1 mM. While anthranilic acid (AA) increased intracellular NAD(+) levels at concentration below 10 MUM in astrocytes. NAD(+) depletion and cell death was observed in AA treated neurons at concentrations above 500 nM. Therefore, the differing responses of astrocytes and neurons to an increase in KP metabolites should be considered when assessing KP toxicity during neuroinflammation. PMID- 22084583 TI - The physiological action of picolinic Acid in the human brain. AB - Picolinic Acid is an endogenous metabolite of L-tryptophan (TRP) that has been reported to possess a wide range of neuroprotective, immunological, and anti proliferative affects within the body. However the salient physiological function of this molecule is yet to be established. The synthesis of picolinic acid as a product of the kynurenine pathway (KP) suggests that, similar to other KP metabolites, picolinic acid may play a role in the pathogenesis of inflammatory disorders within the CNS and possibly other organs.In this paper we review the limited body of literature dealing with the physiological actions of picolinic acid in the CNS and its associated synthesis via the kynurenine pathway in health and disease. Discrepancies and gaps in our current knowledge of picolinic acid are identified highlighting areas of research to promote a more complete understanding of its endogenous function in the brain. PMID- 22084585 TI - Endogenous Kynurenine Aminotransferases Inhibitor is Proposed to Act as "Glia Depressing Factor" (GDF). AB - The endogenous neuroinhibitory amino acid receptor antagonist kynurenic acid (KYNA) has been hypothetically linked to physiological processes and to the pathogenesis of several brain disorders. The aim of this study was to search KYNA metabolism i.e. KYNA levels and enzymes synthesising KYNA kynurenine aminotransferase I and II (KAT I and II) in the central nervous system (CNS) and in the peripheral nervous system. Within the investigated species we found a remarkably low KYNA content (3.4 nM) in piglet's serum compared to rat and human serum. Furthermore, in contrast to high KAT activity present in rat and human livers, a lack of KAT I and KAT II activity was found in piglet liver and other piglet peripheral organs. Therefore we attempted to find a reason for the absence of KYNA formation in piglet peripheral tissue and we researched to find if KYNA formation in rat liver homogenate (measured under standard assay conditions for KAT activity) can be influenced by the application of piglet tissue homogenates and other body fluids. KYNA formation in rat liver homogenate was investigated in the presence of piglet liver, piglet brain, rat brain and human brain homogenates, and also in the presence of cerebrospinal fluid (CSF) of the control and of Multiple Sclerosis patients. We found a significant and dose dependent reduction of rat liver KAT I and KAT II activities in the presence of piglet brain, piglet liver, and human brain, but not in the presence of rat brain homogenate. Interestingly, CSF of the human control subjects significantly lowered rat liver KAT I activity. Furthermore, the inhibitory effect of CSF of Multiple Sclerosis (MS) patients was significantly weaker when compared to the CSF of control subjects. Our data, for the first time, indicated the presence of active component(s)-depressing factor-in the body, which was able to block KYNA formation. Reduced KAT inhibitory effect by CSF of MS patients would suggest a lowered "depressing factor" level in CSF of MS patients and is possibly responsible for an enhancement of KYNA formation and for glia activation and gliosis in the CNS. Subsequently, two fractions obtained after centrifugation of CSF from patients with Neuroborreliosis showed a significantly different ability to block KAT I activity. The CSF-sediment fraction exerts a stronger inhibitory activity than the CSF-supernatant fraction, supporting further the presence of a depressing factor. For the first time, data revealed and demonstrated the ability of endogenous components to block KYNA's synthesis. We propose that a glia depressing factor (GDF), which is abundantly present in the body, might simultaneously control glia cell's KAT activity, respectively KYNA synthesis and also glia proliferation. The mechanism(s) of action, the composition and structure of this factor needs to be further elaborated. PMID- 22084584 TI - Role of the NMDA-receptor in Prepulse Inhibition in the Rat. AB - Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan. Studies have revealed increased brain KYNA levels in patients with schizophrenia. Prepulse inhibition (PPI) is a behavioral model for sensorimotor gating and found to be reduced in schizophrenia. Previous studies have shown that pharmacologically elevated brain KYNA levels disrupt PPI in the rat. The aim of the present study was to investigate the receptor(s) involved in this effect. Rats were treated with different drugs selectively blocking each of the sites that KYNA antagonizes, namely the glutamate recognition site of the N-methyl-D-aspartate receptor (NMDAR), the alpha7* nicotinic acetylcholine receptor (alpha7nAChR) and the glycine site of the NMDAR. Kynurenine (200 mg/kg) was given to replicate the effects of increased levels of KYNA on PPI. In order to block the glutamate recognition site of the NMDAR, CGS 19755 (10 mg/kg) or SDZ 220-581 (2.5 mg/kg) were administered and to antagonize the alpha7nAChR methyllycaconitine (MLA; 6 mg/kg) was given. L-701,324 (1 and 4 mg/kg) or 4-Chloro-kynurenine (4-Cl-KYN; 25, 50 and 100 mg/kg), a drug in situ converted to 7-Chloro-kynurenic acid, were used to block the glycine-site of the NMDAR. Administration of SDZ 220-581 or CGS 19755 was associated with a robust reduction in PPI, whereas L-701,324, 4-Cl-KYN or MLA failed to alter PPI. Kynurenine increased brain KYNA levels 5-fold and tended to decrease PPI. The present study suggests that neither antagonism of the glycine-site of the NMDA receptor nor antagonism of the alpha7nAChR disrupts PPI, rather with regard to the effects of KYNA, blockade of the glutamate recognition site is necessary to reduce PPI. PMID- 22084586 TI - Editorial ISTRY Special Issue. PMID- 22084588 TI - Accelerated tryptophan degradation predicts poor survival in trauma and sepsis patients. AB - Immune system activation and inflammation accompanies immune dysfunction in trauma and sepsis patients. Immunodeficiency may develop in such patients as one consequence of an activated chronic pro-inflammatory response. According to recent data, degradation of L-tryptophan (TRP) via the kynurenine (KYN) pathway by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO) could represent an important contributor to the deficient responsiveness of immunocompetent cells. Compared to healthy controls, patients post trauma or with sepsis had increasing KYN concentrations and KYN to TRP ratios (KYN/TRP) whereas TRP concentrations decreased. Likewise, concentrations of cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and of immune activation marker neopterin increased in patients (all p < 0.001). Furthermore in patients KYN/TRP, KYN and neopterin concentrations were further increasing (all p < 0.001), whereas the changes of TRP, TNF-alpha and IL-6 concentrations were not significant. Compared to the survivors, the non-survivors had a higher concentration of KYN, neopterin, TNF-alpha and IL-6 as well as a higher KYN/TRP ratio. KYN/TRP correlated with neopterin (p < 0.001) and also with TNF-alpha (p < 0.01) and IL-6 concentrations (p < 0.05) and inversely with the in vitro response of stimulated monocytes. We conclude that increased TRP degradation in patients post trauma is closely associated with immune activation. Cytokines released during the pro-inflammatory response may induce the activity of IDO and thus accelerate TRP degradation. Thus, increased IDO activity most likely represents a result of host response to pro-inflammation in patients. Data support a possible role of inflammation-induced IDO in the diminished immunoresponsiveness in patients. PMID- 22084587 TI - On the Biological Importance of the 3-hydroxyanthranilic Acid: Anthranilic Acid Ratio. AB - Of the major components of the kynurenine pathway for the oxidative metabolism of tryptophan, most attention has focussed on the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid, and the glutamate receptor blocker kynurenic acid. However, there is increasing evidence that the redox-active compound 3 hydroxyanthranilic acid may also have potent actions on cell function in the nervous and immune systems, and recent clinical data show marked changes in the levels of this compound, associated with changes in anthranilic acid levels, in patients with a range of neurological and other disorders including osteoporosis, chronic brain injury, Huntington's disease, coronary heart disease, thoracic disease, stroke and depression. In most cases, there is a decrease in 3 hydroxyanthranilic acid levels and an increase in anthranilic acid levels. In this paper, we summarise the range of data obtained to date, and hypothesise that the levels of 3-hydroxyanthranilic acid or the ratio of 3-hydroxyanthranilic acid to anthranilic acid levels, may contribute to disorders with an inflammatory component, and may represent a novel marker for the assessment of inflammation and its progression. Data are presented which suggest that the ratio between these two compounds is not a simple determinant of neuronal viability. Finally, a hypothesis is presented to account for the development of the observed changes in 3-hydroxyanthranilic acid and anthranilate levels in inflammation and it is suggested that the change of the 3HAA:AA ratio, particularly in the brain, could possibly be a protective response to limit primary and secondary damage. PMID- 22084589 TI - Serum levels of tryptophan, 5-hydroxytryptophan and serotonin in patients affected with different forms of amenorrhea. AB - Tryptophan (Trp) is present in the serum, partly bound to albumine and in the free form. The unbound portion of circulating tryptophan has the property of crossing the hematoencephalic barrier and being converted within the brain into serotonin (5-HT) through the enzymatic processes of hydroxylation and decarboxylation. The serotoninergic system plays an important role in neuroendocrine control of reproductive hormone secretion, and in particular, it may influence GnRH pulsatility, a function essential for reproductive processes. In this study, we analysed serum levels of tryptophan, serotonin and 5 hydroxytryptophan (5-HTP) in women with three different forms of amenorrhea: 16 patients were diagnosed with anorexia nervosa, 60 patients with functional hypothalamic amenorrhea, and 14 patients with hyperprolactinemia. Data were compared with those of a group of 25 healthy women. Serum Trp levels were significantly (P <= 0.05) lower in the anorexic (11.64 +/- 0.53 MUg/ml, mean +/- S.E.) than in the control (12.98 +/- 0.37 MUg/ml) groups. In addition, in the anorexic group a statistical dispersion of Trp values was shown indicating a bimodal data distribution suggesting the existence of two different subgroups of patients. Regarding 5-HTP, an increase of its serum level was observed in all the groups with amenorrhea with the highest value in hyperprolactinemic patients. On the contrary, no statistical differences in serum 5-HT levels among the four analyzed groups were observed.This study shows that women affected by various forms of amenorrhea present an altered metabolism of tryptophan via serotonin and, in particular, markedly high differences are observed between the two subgroups of anorexic patients. PMID- 22084590 TI - Indoleamine 2,3-dioxygenase in human hematopoietic stem cell transplantation. AB - In recent years tryptophan metabolism and its rate limiting enzyme indoleamine 2,3-dioxygenase (IDO) have attracted increasing attention for their potential to modulate immune responses including the regulation of transplantation tolerance. The focus of this review is to discuss some features of IDO activity which particularly relate to hematopoietic stem cell transplantation (HSCT). HSCT invariably involves the establishment of some degree of a donor-derived immune system in the recipient. Thus, the outstanding feature of tolerance in HSCT is that in this type of transplantation it is not rejection, which causes the most severe problems to HSCT recipients, but the reverse, graft-versus-host (GvH) directed immune responses. We will discuss the peculiar role of IDO activity and accelerated tryptophan metabolism at the interface between immune activation and immune suppression and delineate from theoretical and experimental evidence the potential significance of IDO in mediating tolerance in HSCT. Finally, we will examine therapeutic options for exploitation of IDO activity in the generation of allo-antigen-specific tolerance, i.e. avoiding allo-reactivity while maintaining immunocompetence, in HSCT. PMID- 22084591 TI - Proteasomal Degradation of Indoleamine 2,3-Dioxygenase in CD8 Dendritic Cells is Mediated by Suppressor of Cytokine Signaling 3 (SOCS3). AB - Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step of tryptophan catabolism in a specific pathway, resulting in a series of extracellular messengers collectively known as kynurenines. IDO has been recognized as an authentic regulator of immunity not only in mammalian pregnancy, but also in infection, autoimmunity, inflammation, allergy, transplantation, and neoplasia. Its suppressive effects are mostly mediated by dendritic cells (DCs) and involve tryptophan deprivation and/or production of kynurenines, which act on IDO-negative DCs as well as CD4(+) and CD8(+) T cells. We have found that mouse IDO contains two tyrosine residues within two distinct putative immunoreceptor tyrosine-based inhibitory motifs, VPY(115)CEL and LLY(253)EGV. We have also found that Suppressor of Cytokine Signaling 3 (SOCS3)-known to interact with phosphotyrosine-containing peptides and be selectively induced by interleukin 6 (IL-6)-binds mouse IDO, recruits the ECS (Elongin-Cullin-SOCS) E3 ligase, and targets the IDO/SOCS3 complex for proteasomal degradation. This event underlies the ability of IL-6 to convert otherwise tolerogenic, IDO-competent DCs into immunogenic cells. Thus onset of immunity in response to antigen within an early inflammatory context demands that IDO be degraded in tolerogenic DCs. These studies support the finding that IDO is regulated by proteasomal degradation in response to immunogenic and inflammatory stimuli. PMID- 22084592 TI - Effects of acute tryptophan depletion on three different types of behavioral impulsivity. AB - INTRODUCTION: While central nervous system serotonin has been implicated in a variety of problematic impulsive behaviors, biological manipulation of brain serotonin using acute tryptophan depletion for studying changes in impulsive behavior has received little attention. METHODS: Using identical treatment conditions, we examined the effects of reduced serotonin synthesis for each of three matched groups using acute tryptophan depletion. Thirty healthy men and women (ages 18-45) were assigned to perform one of three tasks assessing different types of behavioral impulsivity: response initiation, response inhibition, and consequence sensitivity (N = 90). Participants completed two experimental days during which each consumed either a tryptophan-depletion or balanced-placebo amino-acid formulation and completed 5 sessions of their respective tasks at 0.25 h before and 1.5, 4.0, 5.0, and 6.0 h after beverage consumption. RESULTS: During peak effectiveness (5.0 h to 6.0 h following amino acid consumption), depletion produced selective differences dependent on the type of impulsivity being tested. Specifically, relative to baseline testing (pre depletion), response initiation impulsivity was significantly increased during the peak effects of depletion. And, when compared to placebo control, both response initiation and consequence sensitivity impulsivity were increased during the peak effects of depletion. CONCLUSION: Though response initiation and consequence sensitivity impulsivity were affected by tryptophan depletion, response inhibition impulsivity was not, suggesting that other biological processes may underlie this specific component of impulsivity. Future research in other populations or using different pharmacological agents is warranted to further examine the biological processes underlying these components of impulsivity. PMID- 22084593 TI - IDO-Mediated Tryptophan Degradation in the Pathogenesis of Malignant Tumor Disease. AB - Immune escape is a fundamental trait of cancer in which the Th1-type cytokine interferon- gamma (IFN-gamma) seems to play a key role. Among other tumoricidal biochemical pathways, IFN-gamma induces the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in a variety of cells including macrophages, dendritic cells (DCs) and tumor cells. IDO activity has been shown to reflect the extent and the course in a plethora of malignancies including prostate, colorectal, pancreatic, cervical, endometrial, gastric, lung, bladder, ovarian, esophageal and renal cell carcinomas, glioblastomas, mesotheliomas, and melanomas. Furthermore IDO activity during malignant tumor diseases seems to be part of the tumoricidal immune defense strategy, which in the long run is detrimental to the host, when tryptophan deprivation and production of pro apoptotic tryptophan catabolites counteract T-cell responsiveness. PMID- 22084595 TI - Kynurenine Pathway Metabolism is Involved in the Maintenance of the Intracellular NAD Concentration in Human Primary Astrocytes. AB - Efficient synthesis of NAD(+) is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s) by which cells of the central nervous system produce NAD(+). The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP) and de novo NAD(+) synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD(+) levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD(+) levels after 24 hrs. This decrease in NAD(+) was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide. PMID- 22084597 TI - Alzheimer's and seizures: interleukin-18, indoleamine 2,3-dioxygenase and quinolinic Acid. AB - Emergent seizures are common in Alzheimer's disease (AD), although the mechanisms mediating this are unknown. It is proposed that stress induced interleukin-18 (IL 18), via interferon-gamma (IFNy) and independently, increases indoleamine 2,3 dioxygenase (IDO) and subsequent quinolinic acid (QA) in microglia. QA increases seizures and concurrently contributes to neuronal loss via excitotoxicity. The ApoE4 allele interacts with IL-18 polymorphisms to increase the risk of AD, and seems likely to potentiate the emergence of seizures. Concurrent changes in IDO and the kynurenine pathways at the blood-brain-barrier (BBB) have implications for treatment, including in the efficacy of different anti-hypertensives. Melatonin is proposed to inhibit these overlapping excitotoxic and neurodegenerative processes, and would be a useful adjunctive treatment. PMID- 22084596 TI - Understanding the roles of the kynurenine pathway in multiple sclerosis progression. AB - The kynurenine pathway (KP) is a major degradative pathway of tryptophan ultimately leading to the production of nicotinamide adenine dinucleotide (NAD(+)) and is also one of the major regulatory mechanisms of the immune response. The KP is known to be involved in several neuroinflammatory disorders including Alzheimer's disease, amyotrophic lateral sclerosis, AIDS dementia complex, Parkinson's disease, schizophrenia, Huntington's disease and brain tumours. However, the KP remains a relatively new topic for the field of multiple sclerosis (MS). Over the last 2-3 years, some evidence has progressively emerged suggesting that the KP is likely to be involved in the pathogenesis of autoimmune diseases especially MS. Some KP modulators are already in clinical trials for other inflammatory diseases and would potentially provide a new and important therapeutic strategy for MS patients. This review summarizes the known relationships between the KP and MS. PMID- 22084594 TI - Tryptophan, Neurodegeneration and HIV-Associated Neurocognitive Disorder. AB - This review presents an up-to-date assessment of the role of the tryptophan metabolic and catabolic pathways in neurodegenerative disease and HIV-associated neurocognitive disorder. The kynurenine pathway and the effects of each of its enzymes and products are reviewed. The differential expression of the kynurenine pathway in cells within the brain, including inflammatory cells, is explored given the increasing recognition of the importance of inflammation in neurodegenerative disease. An overview of common mechanisms of neurodegeneration is presented before a review and discussion of the evidence for a pathogenetic role of the kynurenine pathway in Alzheimer's disease, HIV-associated neurocognitive disorder, Huntington's disease, motor neurone disease, and Parkinson's disease. PMID- 22084598 TI - Rapid Isocratic Liquid Chromatographic Separation and Quantification of Tryptophan and Six kynurenine Metabolites in Biological Samples with Ultraviolet and Fluorimetric Detection. AB - A simple, rapid isocratic liquid chromatographic procedure with ultraviolet and fluorimetric detection is described for the separation and quantification of L tryptophan (Trp) and six of its kynurenine metabolites (kynurenine, 3 hydroxykynurenine, and 3-hydroxyanthranilic, kynurenic, xanthurenic and anthranilic acids). Using the Perkin Elmer LC 200 system, a reverse phase Synergi 4 MU fusion-RP80 A column (250 * 4.6 mm) (Phenomenex), and a mobile phase of 10 mM sodium dihydrogen phosphate: methanol (73:27, by vol) at pH 2.8 and a flow rate of 1.0-1.2 ml/min at 37 degrees C, a run took ~13 min. The run took <7 min at 40 degrees C and a 1.4 ml/min flow rate. Limits of detection of all 7 analytes were 5-72 nM and their recoveries from human plasma and rat serum and liver varied between 62% and 111%. This simple method is suitable for high throughput work and can be further developed to include quinolinic acid and other Trp metabolites. PMID- 22084599 TI - Tryptophan oxidative metabolism catalyzed by geobacillus stearothermophilus: a thermophile isolated from kuwait soil contaminated with petroleum hydrocarbons. AB - Tryptophan metabolism has been extensively studied in humans as well as in soil. Its metabolism takes place mainly through kynurenine pathway yielding hydroxylated, deaminated and many other products of physiological significance. However, tryptophan metabolism has not been studied in an isolated thermophilic bacterium. Geobacillus stearothermophilus is a local thermophile isolated from Kuwait desert soil contaminated with petroleum hydrocarbons. The bacterium grows well at 65 degrees C in 0.05 M phosphate buffer (pH 7), when supplied with organic compounds as a carbon source and has a good potential for transformation of steroids and related molecules. In the present study, we used tryptophan ethyl ester as a carbon source for the bacterium to study the catabolism of the amino acid at pH 5 and pH 7. In this endeavor, we have resolved twenty one transformation products of tryptophan by GC/LC and have identified them through their mass spectral fragmentation. PMID- 22084600 TI - Tryptophan transport in human fibroblast cells-a functional characterization. AB - There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to identify the main transporters of tryptophan in fibroblast cell lines from healthy controls.Tryptophan kinetic parameters (V(max) and K(m)) at low and high concentrations were measured in fibroblasts using the cluster tray method. Uptake of (3)H (5)-L-tryptophan at different concentrations in the presence and absence of excess concentrations of inhibitors or combinations of inhibitors of amino acid transporters were also measured. Tryptophan transport at high concentration (0.5 mM) had low affinity and high V(max) and the LAT1 isoform of system-L was responsible for approximately 40% of the total uptake of tryptophan. In comparison, tryptophan transport at low concentration (50 nM) had higher affinity, lower V(max) and approximately 80% of tryptophan uptake was transported by system-L with LAT1 as the major isoform. The uptake of tryptophan at the low concentration was mainly sodium (Na(+)) dependent, while uptake at high substrate concentration was mainly Na(+) independent. A series of different transporter inhibitors had varying inhibitory effects on tryptophan uptake.This study indicates that tryptophan is transported by multiple transporters that are active at different substrate concentrations in human fibroblast cells. The tryptophan transport trough system-L was mainly facilitated by the LAT1 isoform, at both low and high substrate concentrations of tryptophan. PMID- 22084601 TI - Effects of Kynurenine Pathway Inhibition on NAD Metabolism and Cell Viability in Human Primary Astrocytes and Neurons. AB - The kynurenine pathway (KP) is the principle route of L-Tryptophan (TRP) metabolism, producing several neurotoxic and neuroprotective metabolic precursors before complete oxidation to the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD(+)). KP inhibition may prove therapeutic in central nervous system (CNS) inflammation by reducing the production of excitotoxins such as quinolinic acid (QUIN). However, KP metabolism may also be cytoprotective through the de novo synthesis of intracellular NAD(+). We tested the hypothesis that the KP is directly involved in the maintenance of intracellular NAD(+) levels and SIRT1 function in primary astrocytes and neurons through regulation of NAD(+) synthesis. Competitive inhibition of indoleamine 2,3 dioxygenase (IDO), and quinolinic acid phosphoribosyltransferase (QPRT) activities with 1-methyl-L Tryptophan (1-MT), and phthalic acid (PA) respectively, resulted in a dose dependent decrease in intracellular NAD(+) levels and sirtuin deacetylase-1 (SIRT1) activity, and correlated directly with reduced cell viability. These results support the hypothesis that the primary role of KP activation during neuroinflammation is to maintain NAD(+) levels through de novo synthesis from TRP. Inhibition of KP metabolism under these conditions can compromise cell viability, NAD-dependent SIRT1 activity and CNS function, unless alternative precursors for NAD(+) synthesis are made available. PMID- 22084602 TI - L-Tryptophan Production by Auxotrophic and Analogue Resistant Mutants of Aureobacterium flavescens. AB - A number of tyrosine plus phenylalanine double auxotrophic mutants were isolated by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) treatment of a locally isolated strain of Aureobacterium flavescens of which 11A(39) and 11A(17) were selected on the basis of their tryptophan production in a mineral salt medium over other isolated mutant strains. The mutational block in the aromatic amino acid biosynthetic pathway of the selected double auxotrophs were determined. By controlling pH of the production medium to near neutrality, the active growth period could be extended up to 72 h and more tryptophan was accumulated compared to pH unregulated culture where the active growth ceased after 48 h. Further improvement of the tryptophan production has been achieved by stepwise isolation of a mutant strain resistant to the tryptophan analogues p-fluorotryptophan (FT) and 5-methyl tryptophan (MT) from the 11A(39). Demand for L-tryptophan as food additive and therapeutic agent is increasing day by day throughout the World, particularly in the underdeveloped and developing countries like India. Still to date India depends on other countries for L-tryptophan. The aim of this work is to develop a potent high yielding, feed back insensitive mutant strain and optimization of its medium pH for maximum production of tryptophan. PMID- 22084603 TI - Kynurenine pathway Hypothesis: The nature of the chronic Fatigue syndrome (cFs) Revisited. PMID- 22084604 TI - Diffuse Idiopathic Skeletal Hyperostosis (DISH)-A Rare Etiology of Dysphagia. AB - A 72-year-old gentleman presented to the hospital with progressively worsening dysphagia to soft foods and liquids. He was diagnosed with severe pharyngeal dysphagia by modified barium swallow. A CT scan of the neck with IV contrast showed anterior flowing of bridging osteophytes from C3-C6, indicative of DISH, resulting in esophageal impingement. He underwent resection of the DISH segments. Following the surgery, a PEG tube for nutrition supplementation was placed. However, the PEG tube was removed after five months when the speech and swallow evaluation showed no residual dysphagia. DISH is a rare non-inflammatory condition that results in pathological ossification and calcification of the anterolateral spinal ligaments. PMID- 22084605 TI - Asymptomatic pulmonary hypertension in systemic lupus erythematosus. AB - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious and often fatal complication of systemic lupus erythematosus (SLE). Because the diagnosis of PAH often is made years after symptom onset, early diagnostic strategies are essential. Doppler echocardiography currently is considered the noninvasive screening test of choice for evaluating pulmonary hypertension. AIM: Screening for asymptomatic pulmonary hypertension in systemic lupus erythematosus patients using Doppler echocardiography, and correlating it with inflammatory parameters of the disease. PATIENTS AND METHODS: Doppler echocardiography was performed in 74 patients with systemic lupus erythematosus over one year (66 adult and 8 juvenile), adult SLE included 57 patients with adult-onset and 9 patients with childhood-onset. Pulmonary hypertension was diagnosed if the peak systolic pressure gradient at the tricuspid valve was more than 30 mmHg. All patients were subjected to full history taking, rheumatological examination, laboratory studies and chest x-ray. RESULTS: In seventy four SLE patients, the pulmonary hypertension was detected in 8 patients (10.8%), 7 adult-onset SLE patients (aged from 19 to 30 years) and 1 juvenile SLE (aged 12 years). The range of pulmonary artery systolic pressure was 34-61.2 mmHg (43.19 +/- 9.28). No significant differences between patients with and those without pulmonary hypertension as regard clinical features. Significantly higher frequencies of rheumatoid factor and anti-cardiolipin antibodies were found in patients with pulmonary hypertension versus those without (P = 0.02, P = 0.008 respectively). Positive rheumatoid factor and ACL were significantly associated with occurrence of PAH in SLE (P = 0.007, P = 0.006 respectively). No significant correlations were found between pulmonary artery pressure, disease duration, SLE Disease Activity Index (SLEDAI), ESR, and anti-ds DNA. CONCLUSION: Patients with SLE have an increased risk of pulmonary arterial hypertension. Echocardiography should be used as a screening tool in patients at high risk for development of pulmonary hypertension. Positive anti-cardiolipin antibodies and rheumatoid factor were significant predictors of pulmonary hypertension in our study. PMID- 22084606 TI - Bone mineral density changes in patients with recent-onset rheumatoid arthritis. AB - BACKGROUND: Osteoporosis and related fragility fractures are one of the most common complications seen in patients with rheumatoid arthritis (RA) and dramatically affect quality of life. OBJECTIVE: To evaluate changes in bone mineral density in patients with recent onset rheumatoid arthritis (<1 year) and its correlation if any with a modified DAS-28 score and simple erosion narrowing score (SENS). METHODS: This study included 30 patients with recent-onset rheumatoid arthritis fulfilling the new American College of Rheumatology/European League Against Rheumatism diagnostic criteria for rheumatoid arthritis and 20 healthy volunteers as controls. All were subjected to a complete blood count, erythrocyte sedimentation rate, C-reactive protein, liver function tests, renal function tests, rheumatoid factor, and plain x-rays of the hands and feet. Dual energy x-ray absorptiometry DEXA was used to measure bone mineral density (BMD) of the left proximal femur, lumbar spine (L1-L4), and lower distal radius at the time of recruitment. RESULTS: In the RA patients, 13.3% had osteoporosis, 50% had osteopenia, and 36.7% had normal BMD. The most common site of osteoporosis was the lumbar spine (four patients, 13.3%) followed by the femur (two patients, 6.6%), and forearm (only one patient, 3.3%). There was a significantly higher percentage of osteoporosis among RA males than females and the difference was statistically significant (P = 0.009). Osteoporosis was more common in patients treated with corticosteroids and disease modifying antirheumatic drugs (DMARDs) than in patients treated with only nonsteroidal anti-inflammatory drugs (P = 0.004). Higher disease activity (DAS-28) was found in RA patients with osteoporosis compared to RA patients with normal BMD or osteopenia, but the difference was not statistically significant. Osteoporotic RA patients were found to have a higher SENS score for radiological damage than nonosteoporotic ones. CONCLUSION: BMD changes do occur in patients with early RA, and are not necessarily correlated with disease activity (DAS-28). However, a significant negative correlation was found between BMD and the score of radiological damage (SENS). Dual energy x-ray absorptiometry is an important investigation to assess BMD in early RA patients. PMID- 22084607 TI - Extended release niacin-laropiprant in patients with hypercholesterolemia or mixed dyslipidemias improves clinical parameters. AB - The progression of atherosclerosis remains a major cause of morbidity and mortality. Plaque formation is an immunological response driven by a number of risk factors, and reduction of risk is the primary goal of treatment. The role of LDL-C is well established and statins have proved effective drugs, although the relative risk reduction is only around 30%. The importance of other factors notably low HDL-C and high TGs-has become increasingly clear and the search for alternative strategies continues. Niacin is particularly effective in achieving normalization of HDL-C but is clinically underutilized due to the side effect of cutaneous flushing. The discovery that flushing is mediated by mechanisms distinct from the lipid-lowering effects has led to the development of combination drugs with reduced side effects. This review considers the evidence regarding the clinical efficacy of extended-release niacin and the DP1 antagonist laropiprant in the treatment of hypercholesterolemia and mixed dyslipidemias. PMID- 22084609 TI - Bihemispheric subcortical infarcts in the middle cerebral artery territory. AB - BACKGROUND AND PURPOSE: Previous studies have suggested embolic mechanisms for bihemispheric subcortical infarcts involving the anterior and posterior circulation. However, the mechanism of bihemispheric subcortical infarcts in middle cerebral artery (MCA) territories remains uncertain. We describe a patient with acute bihemispheric subcortical infarcts in restricted MCA territories suggesting an embolic mechanism. CASE DESCRIPTION: A 62-year-old woman with a history of hypertension and hyperlipidemia suddenly presented with left hemiplegia. Diffusion-weighted and T(2)-weighted magnetic resolution imaging of the brain showed multiple subcortical high intensity in the MCA territories. There were no acute infarctions in the cerebrum, brain stem, or cerebellum, including cortical lesions. The patient had no carotid, internal carotid artery, or MCA disease. CONCLUSION: Bihemispheric subcortical infarcts in the MCA territory are likely to have a proximal embolic source and such infarcts could be associated with multiple subcortical infarcts due to small vessel disease. PMID- 22084608 TI - Safety and efficacy of dronedarone in the treatment of atrial fibrillation/flutter. AB - Dronedarone is an amiodarone analog but differs structurally from amiodarone in that the iodine moiety was removed and a methane-sulfonyl group was added. These modifications reduced thyroid and other end-organ adverse effects and makes dronedarone less lipophilic, shortening its half-life. Dronedarone has been shown to prevent atrial fibrillation/flutter (AF/AFl) recurrences in several multi center trials. In addition to its rhythm control properties, dronedarone has rate control properties and slows the ventricular response during AF. Dronedarone is approved in Europe for rhythm and rate control indications. In patients with decompensated heart failure, dronedarone treatment increased mortality and cardiovascular hospitalizations. However, when dronedarone was used in elderly high risk AF/AFl patients excluding such high risk heart failure, cardiovascular hospitalizations were significantly reduced and the drug was approved in the USA for this indication in 2009 by the Food and Drug Administration. Updated guidelines suggest dronedarone as a front-line antiarrhythmic in many patients with AF/Fl but caution that the drug should not be used in patients with advanced heart failure. In addition, the recent results of the PALLAS trial suggest that dronedarone should not be used in the long-term treatment of patients with permanent AF. PMID- 22084610 TI - A case of cutaneous infection caused by mycobacterium szulgai with progression to acute respiratory distress syndrome. AB - A 59-year-old man presented with a skin eruption and bilateral swelling of the legs. Soon after the initial presentation, he developed acute respiratory distress syndrome (ARDS) with miliary lung nodules. Culture of samples from the skin ulcers, sputum, and bronchoalveolar lavage fluid all revealed Mycobacterium szulgai infection. The patient was successfully treated with antituberculosis drugs. M. szulgai infection is very rarely reported worldwide, and disseminated infection usually occurs in immunocompromised patients. However, the present patient was a non-immunocompromised case, although he was a hepatitis B virus carrier. While the progression to ARDS from M. tuberculosis infection is well known, this is the first case of M. szulgai infection progressing to ARDS. PMID- 22084611 TI - Traumatic Abdominal Wall Hernia: A Case Report of High-Energy Type without Surgical Repair. AB - Repair of traumatic abdominal wall hernia (TAWH) has been reported to be necessary. Reported here is one case of TAWH without repair. A 27-year-old man was accidentally sandwiched between a rock and a truck and admitted to our emergency department. There was a swelling of 10 cm in the right upper quadrant of the abdomen. The enhanced computed tomographic scan demonstrated a large abdominal wall muscular defect, transverse colon protrusion, and the presence of subcutaneous emphysema at the site. Based on these findings, lacerated transverse colon entrapped in TAWH was diagnosed. The patient underwent emergency laparotomy for laceration of the transverse colon, duodenum and pancreas, and open book fracture of the pelvis. Repair of the hernia was not performed because of the possibility of abscess formation by stool contamination. However, the hernia disappeared and the patient is doing well without recurrence of hernia 16 months after injury. PMID- 22084612 TI - Spontaneous Transient Lateral Thoracic Lung Herniation Resulting in Systemic Inflammatory Response Syndrome (SIRS) and Subsequent Contralateral Lung Injury. AB - Lung herniation is a relatively rare clinical entity that is most commonly either congenital or acquired traumatically. We describe a case of spontaneous lung herniation secondary to acute cough in an obese male smoker complicated by contralateral acute lung injury and systemic inflammatory response syndrome (SIRS). Mechanisms of lung herniation, classification, diagnosis, and management will be discussed. PMID- 22084613 TI - A boy with non-herpes simplex acute limbic encephalitis and antiglutamate receptor antibodies. AB - This report concerns a 12-year-old male with intractable seizures over a long period. The case fulfilled the diagnostic criteria for nonherpetic acute limbic encephalitis. He had frequent convulsions starting with a partial seizure at the left angle of the mouth and progressing to secondary generalized seizures. He was treated with several anticonvulsants, combined with methylprednisolone and gamma globulin under mechanical ventilation. However, his convulsions reappeared after tapering of the barbiturate. His magnetic resonance imaging showed a high intensity area in the hippocampus by FLAIR and diffusion. After five months he recovered without serious sequelae. Virological studies, including for herpes simplex virus, were all negative. He was transiently positive for antiglutamate receptor antibodies in cerebrospinal fluid and serum. PMID- 22084614 TI - Treatment with etanercept in a patient with rheumatoid arthritis-associated interstitial lung disease. AB - We report a case of a 52-year-old woman with a 1-year history of rheumatoid arthritis-associated interstitial lung disease referred to hospital because of aggravated pulmonary symptoms in spite of intensive treatment including prednisone, azathioprine and triptergium glycoside. We subsequently initiated treatment with 25 mg of etanercept, subcutaneously injected twice weekly. Following 6 months of therapy with this agent, sustained improvement in dyspnea, cough was reported by the patient and respiratory function test showed marked improvement. The improvement was confirmed by reduced middle and lower lung markings on chest radiography and high-resolution CT scan. This report suggests etanercept may be effective in the treatment of rheumatoid arthritis-associated interstitial lung disease. PMID- 22084615 TI - Reduced hypoxia risk in a systemic sclerosis patient with interstitial lung disease after long-term pulmonary rehabilitation. AB - Pulmonary rehabilitation is effective for improving exercise capacity in patients with interstitial lung disease (ILD), and most programs last about 8 weeks. A 43 year-old male patient with systemic sclerosis and oxygen saturation (SpO(2)) declining because of severe ILD was hospitalized for treatment of chronic skin ulcers. During admission, he completed a 27-week walking exercise program with SpO(2) monitoring. Consequently, continuous walking distance without severe hypoxia (SpO(2) > 90%) increased from 60 m to 300 m after the program, although his six-minute walking distance remained the same. This suggests that walking exercise for several months may reduce the risk of hypoxia in patients with ILD, even though exercise capacity does not improve. PMID- 22084616 TI - Arterial stiffness in lower limb amputees. AB - BACKGROUND: A high carotid-femoral pulse wave velocity (PWV) has been related to increased cardiovascular morbidity and mortality, but has not been previously evaluated in amputees. The aim of this study was to compare PWV between amputees and nonamputees. METHODS: In this cross-sectional study, data were collected from 60 male lower limb amputees and 86 male age-matched nonamputees. PWV was measured noninvasively using a Complior((r)) device. All participants underwent laboratory investigations and anthropometry. The difference in PWV between amputee and nonamputees was estimated. Multivariate regression was used to adjust for differences between the groups as a result of potential confounders. RESULTS: PWV was higher in amputees than in nonamputees (10.8 +/- 1.9 m/sec versus 9.9 +/- 1.8 m/sec, P = 0.008, respectively). This difference remained even after adjusting for confounding factors. CONCLUSION: A higher PWV was demonstrated in lower limb amputees. Routine assessment of PWV may contribute to cardiovascular risk stratification in amputees. PMID- 22084617 TI - Roflumilast, a Novel Phosphodiesterase 4 Inhibitor, for COPD Patients with a History of Exacerbations. AB - Acute exacerbations of COPD (AECOPD) are major clinical events. They are associated with a more rapid decline in lung function, poorer quality of life scores, and an increased risk of dying. Exacerbations that require hospitalization have particular significance. Approximately 40% of the AECOPD patients who require hospitalization will die in the subsequent year. Since many AECOPD require hospitalization, they account for most of the expense of caring for COPD patients. Treatment with long-acting bronchodilators and combination inhaled corticosteroid/long-acting bronchodilator inhalers reduces but does not eliminate AECOPD. Roflumilast, a selective phosphodiesterase 4 (PDE4) inhibitor, is an anti-inflammatory medication that improves lung function in patients with COPD. In patients with more severe airway obstruction, clinical features of chronic bronchitis, and a history of AECOPD, roflumilast reduces the frequency of AECOPD when given in combination with short-acting bronchodilators, long-acting bronchodilators, or inhaled corticosteroids. It is generally well tolerated but the most common adverse effects include diarrhea, nausea, weight loss, and headaches. In clinical trials, patients treated with roflumilast experienced weight loss that averaged just over 2 kg but was primarily due to the loss of fat tissue. Weight loss was least in underweight patients and obese patients experienced the greatest weight loss. An unexpected benefit of treatment with roflumilast was that fasting blood glucose and hemoglobin A1c levels improved in patients with comorbid type 2 diabetes mellitus. Roflumilast, the first selective PDE4 inhibitor to be marketed, is a promising drug for the management of COPD patients with more severe disease. PMID- 22084618 TI - Sleep insufficiency, sleep health problems and performance in high school students. AB - A survey on sleep schedule, sleep health, school performance and school start times was conducted in 1,941 adolescents. A high level of early and circadian disadvantaged sleep/wake schedules during weekdays was observed. Shorter sleep duration on weekdays was reported, especially in upper classmen. Complaints of inadequate sleep and sleepiness during weekdays, alarm clock use, and napping were prevalent. Night awakening and prolonged sleep onset were common and associated with poor school performance. Students with a sleep length of less than 7 hours on both weekdays and weekends exhibited poorer performance, while those who made up this sleep loss on weekends did not. The total number of poor sleep factors in an individual also correlated with poor school performance. Earlier school start times were associated with a perception of poor sleep quality, shorter sleep duration and more sleep health problems. We conclude that sleep inadequacies and sleep health problems were prevalent in this population, especially in those who started school earlier in the morning, and that these poor sleep factors were associated with school performance. PMID- 22084620 TI - Antitumor Efficacy of Intravesical BCG, Gemcitabine, Interferon-alpha and Interleukin-2 as Mono- or Combination-Therapy for Bladder Cancer in an Orthotopic Tumor Model. AB - OBJECTIVE: To reduce adverse effects and improve efficacy of intravesical BCG for bladder cancer, alternative treatment options were investigated in an orthotopic rat tumor model. METHODS: Superficial bladder cancer was established in syngeneic female rat bladders by instillation of AY-27 cells. Animals were randomly assigned to treatment groups including dose escalation of intravesical BCG with or without interferon-alpha (IFN-alpha) or interleukin-2 (IL-2); or graded doses of gemcitabine alone; or BCG plus gemcitabine. Treatments were given twice weekly for 3 weeks. Rats in control groups received saline instillations. Treatment response was monitored by animals' well-being, survival days, tumor growth inhibition, and histological examination at necropsy. RESULTS: Rats receiving monotherapy with intravesical BCG, gemcitabine, or IFN-alpha, attained significantly better survival and tumor reduction compared with control (P = 0.002; 0.001; 0.002, respectively, Log-rank Test). A dose-dependent treatment response was observed in animals with established bladder tumor receiving escalated BCG instillations. Only high-dose BCG significantly improved animal survival. Although high-dose BCG plus gemcitabine or IFN-alpha did not increase benefit over monotherapies, low-dose BCG plus IL-2 did show improved efficacy (P = 0.01). CONCLUSION: Intravesical monotherapies with gemcitabine and IFN-alpha were as effective as BCG for treatment of early non-muscle-invasive urothelial bladder cancer in this immune competent rat model. Combining these agents with high-dose BCG did not further increase efficacy. However, combining low-dose BCG with IL-2 enhanced BCG effectiveness. PMID- 22084621 TI - Management Options in Advanced Prostate Cancer: What is the Role for Sipuleucel T? AB - Most prostate cancer-related deaths occur in patients with castration-resistant prostate cancer (CRPC). Until recently, only therapy with docetaxel and prednisone has been shown to prolong survival in men with metastatic CRPC. With the United States Food and Drug Administration (US FDA) approvals of sipuleucel T, cabazitaxel, and abiraterone acetate, all based on improvement in overall survival, the landscape for management of men with metastatic CRPC has dramatically changed. In this review we will discuss the pivotal clinical trial data leading to these approvals, with particular focus on the unique indication for sipuleucel-T and the implications for optimal management and sequencing of treatment in this patient population. PMID- 22084622 TI - Tyrosine kinase inhibitors in the treatment of advanced renal cell carcinoma: focus on pazopanib. AB - Advances in our understanding of renal cancer biology have led to a new treatment paradigm in renal cancer. Tyrosine kinase inhibitors (TKI), that target the intracellular kinase domain of the VEGF receptor, have become established as the most successful class of agent in this disease. Three TKIs are currently approved for use in patients with advanced disease. Newer, more potent inhibitors have reached phase III clinical testing, meaning others are likely to follow. In 2009, pazopanib became the most recent TKI to receive FDA approval. This review sets out to discuss the key opportunities and challenges associated with TKI use in RCC, focusing particularly on pazopanib. We also review the current place of pazopanib in the management of patients with advanced disease, in what is a rapidly evolving therapeutic landscape. PMID- 22084623 TI - Outreach to Improve Patient Education at South Carolina Free Medical Clinics. AB - The University of South Carolina (USC) School of Medicine (SOM) librarians have partnered with eight free medical clinics in South Carolina to enhance patient education efforts. During these outreach projects, project librarians purchased and installed computers, projectors, screens, LCD monitors, and touch-screen information kiosks equipment in each clinic, conducted MedlinePlus training sessions with clinic staff, and added links to MedlinePlus on the patient education area of the clinics' websites. As a result, the free medical clinics incorporated MedlinePlus into their patient education classes or use the self playing tutorials in patient waiting rooms. PMID- 22084624 TI - Fast Track THR: One Hospital's Experience with a 2-Day Length of Stay Protocol for Total Hip Replacement. AB - BACKGROUND: Current trends in total joint replacement have focused on shorter hospital stays. PURPOSE: This study aimed to determine if a pathway for total hip replacement (THR) with the goal of a 2-day discharge (fast track) is safe and effective compared to our traditional pathway (control). METHODS: One hundred forty-nine patients undergoing unilateral, uncomplicated, THR were enrolled in an accelerated postoperative pathway and 134 were enrolled in the traditional pathway. Patients were followed prospectively and outcomes included hospital length of stay, intra- and postoperative complications, readmissions, reoperations. A statistical model was created to determine factors predictive of a 2-day discharge. RESULTS: At 1 year, there were no differences in complications, readmissions, or reoperations. The average length of stay decreased from 4.1 to 2.6 days (p < 0.0001). In the fast track group, 58% of patients were discharged home within 2 days. Barriers to a 2-day discharge were postoperative pain, nausea, and dizziness. The only preoperative factor that was predictive of a 2-day discharge was hypertension. CONCLUSIONS: In a select group of patients, a protocol that allows for a 2-day discharge following THR is safe and effective. PMID- 22084625 TI - Repeated 24-hour recalls versus dietary records for estimating nutrient intakes in a national food consumption survey. AB - BACKGROUND: The methodology used in the first Belgian food consumption survey followed to a large extent the instructions of the European Food Consumption (EFCOSUM) reports, where repeated 24-hour recalls (24HR) using EPIC-SOFT were recommended. OBJECTIVES: To evaluate the relative validity of two non-consecutive 24HR using EPIC-SOFT by comparison with 5-day estimated dietary records (EDR). To assess misreporting in energy for both methods by comparing energy intake with energy expenditure from accelerometery in a subsample. DESIGN: A total of 175 subjects (aged 15 and over) were recruited to participate in the study. Repeated 24HR were performed with an interval of 2-8 weeks. After completion of the second interview, subjects were instructed to keep an EDR. Dietary intakes were adjusted for within-person variability to reflect usual intakes. A Student's t-test was calculated to assess differences between both methods. Spearman and Kappa correlation coefficients were used to investigate agreement. RESULTS: In total, 127 subjects completed the required repeated 24HR, as well as the five record days. From 76 participants, accelerometer data were available. In both methods, about 35% of participants had ratios of Energy Intake/Total Energy Expenditure (EI/TEE) above or below 95% confidence intervals for EI/TEE, suggesting misreporting of energy. Significant differences between the two dietary intake methods were found for total energy, total fat, fatty acids, cholesterol, alcohol, vitamin C, thiamine, riboflavin and iron. In general, intakes from 24HR were higher compared to EDR. Correlation coefficients for all nutrients ranged from 0.16 for thiamine to 0.70 for water. CONCLUSIONS: The results from this study show that in the context of nutritional surveillance, duplicate 24HR can be used to asses intakes of protein, carbohydrates, starch, sugar, water, potassium and calcium. PMID- 22084619 TI - Inhibitors of Glioma Growth that Reveal the Tumour to the Immune System. AB - Treated glioblastoma patients survive from 6 to 14 months. In the first part of this review, we describe glioma origins, cancer stem cells and the genomic alterations that generate dysregulated cell division, with enhanced proliferation and diverse response to radiation and chemotherapy. We review the pathways that mediate tumour cell proliferation, neo-angiogenesis, tumor cell invasion, as well as necrotic and apoptotic cell death. Then, we examine the ability of gliomas to evade and suppress the host immune system, exhibited at the levels of antigen recognition and immune activation, limiting the effective signaling between glioma and host immune cells.The second part of the review presents current therapies and their drawbacks. This is followed by a summary of the work of our laboratory during the past 20 years, on oligosaccharide and glycosphingolipid inhibitors of astroblast and astrocytoma division. Neurostatins, the O-acetylated forms of gangliosides GD1b and GT1b naturally present in mammalian brain, are cytostatic for normal astroblasts, but cytotoxic for rat C6 glioma cells and human astrocytoma grades III and IV, with ID50 values ranging from 200 to 450 nM. The inhibitors do not affect neurons or fibroblasts up to concentrations of 4 MUM or higher.At least four different neurostatin-activated, cell-mediated antitumoral processes, lead to tumor destruction: (i) inhibition of tumor neovascularization; (ii) activation of microglia; (iii) activation of natural killer (NK) cells; (iv) activation of cytotoxic lymphocytes (CTL). The enhanced antigenicity of neurostatin-treated glioma cells, could be related to their increased expression of connexin 43. Because neurostatins and their analogues show specific activity and no toxicity for normal cells, a clinical trial would be the logical next step. PMID- 22084626 TI - Climate change and environmental impacts on maternal and newborn health with focus on Arctic populations. AB - BACKGROUND: In 2007, the Intergovernmental Panel on Climate Change (IPCC) presented a report on global warming and the impact of human activities on global warming. Later the Lancet commission identified six ways human health could be affected. Among these were not environmental factors which are also believed to be important for human health. In this paper we therefore focus on environmental factors, climate change and the predicted effects on maternal and newborn health. Arctic issues are discussed specifically considering their exposure and sensitivity to long range transported contaminants. METHODS: Considering that the different parts of pregnancy are particularly sensitive time periods for the effects of environmental exposure, this review focuses on the impacts on maternal and newborn health. Environmental stressors known to affects human health and how these will change with the predicted climate change are addressed. Air pollution and food security are crucial issues for the pregnant population in a changing climate, especially indoor climate and food security in Arctic areas. RESULTS: The total number of environmental factors is today responsible for a large number of the global deaths, especially in young children. Climate change will most likely lead to an increase in this number. Exposure to the different environmental stressors especially air pollution will in most parts of the world increase with climate change, even though some areas might face lower exposure. Populations at risk today are believed to be most heavily affected. As for the persistent organic pollutants a warming climate leads to a remobilisation and a possible increase in food chain exposure in the Arctic and thus increased risk for Arctic populations. This is especially the case for mercury. The perspective for the next generations will be closely connected to the expected temperature changes; changes in housing conditions; changes in exposure patterns; predicted increased exposure to Mercury because of increased emissions and increased biological availability. CONCLUSIONS: A number of environmental stressors are predicted to increase with climate change and increasingly affecting human health. Efforts should be put on reducing risk for the next generation, thus global politics and research effort should focus on maternal and newborn health. PMID- 22084627 TI - Mapping spikes to sensations. AB - Single-unit recordings conducted during perceptual decision-making tasks have yielded tremendous insights into the neural coding of sensory stimuli. In such experiments, detection or discrimination behavior (the psychometric data) is observed in parallel with spike trains in sensory neurons (the neurometric data). Frequently, candidate neural codes for information read-out are pitted against each other by transforming the neurometric data in some way and asking which code's performance most closely approximates the psychometric performance. The code that matches the psychometric performance best is retained as a viable candidate and the others are rejected. In following this strategy, psychometric data is often considered to provide an unbiased measure of perceptual sensitivity. It is rarely acknowledged that psychometric data result from a complex interplay of sensory and non-sensory processes and that neglect of these processes may result in misestimating psychophysical sensitivity. This again may lead to erroneous conclusions regarding the adequacy of candidate neural codes. In this review, we first discuss requirements on the neural data for a subsequent neurometric-psychometric comparison. We then focus on different psychophysical tasks for the assessment of detection and discrimination performance and the cognitive processes that may underlie their execution. We discuss further factors that may compromise psychometric performance and how they can be detected or avoided. We believe that these considerations point to shortcomings in our understanding of the processes underlying perceptual decisions, and therefore offer potential for future research. PMID- 22084628 TI - The circadian clock, reward, and memory. AB - During our daily activities, we experience variations in our cognitive performance, which is often accompanied by cravings for small rewards, such as consuming coffee or chocolate. This indicates that the time of day, cognitive performance, and reward may be related to one another. This review will summarize data that describe the influence of the circadian clock on addiction and mood related behavior and put the data into perspective in relation to memory processes. PMID- 22084631 TI - MEGen: A Physiologically Based Pharmacokinetic Model Generator. AB - Physiologically based pharmacokinetic models are being used in an increasing number of different areas. However, they are perceived as complex, data hungry, resource intensive, and time consuming. In addition, model validation and verification are hindered by the relative complexity of the equations. To begin to address these issues a web application called MEGen for the rapid construction and documentation of bespoke deterministic PBPK model code is under development. MEGen comprises a parameter database and a model code generator that produces code for use in several commercial software packages and one that is freely available. Here we present an overview of the current capabilities of MEGen, and discuss future developments. PMID- 22084629 TI - Moving forward: advances in the treatment of movement disorders with deep brain stimulation. AB - The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson's disease (PD), tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS) has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced PD can be treated with thalamic, globus pallidus internus (GPi), or subthalamic nucleus (STN) DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. While multiple regions of the brain have been targeted for DBS in the treatment of these movement disorders, this review article focuses on those that are most commonly used in current clinical practice. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted. PMID- 22084630 TI - Modulation of neuronal signal transduction and memory formation by synaptic zinc. AB - The physiological role of synaptic zinc has remained largely enigmatic since its initial detection in hippocampal mossy fibers over 50 years ago. The past few years have witnessed a number of studies highlighting the ability of zinc ions to regulate ion channels and intracellular signaling pathways implicated in neuroplasticity, and others that shed some light on the elusive role of synaptic zinc in learning and memory. Recent behavioral studies using knock-out mice for the synapse-specific zinc transporter ZnT-3 indicate that vesicular zinc is required for the formation of memories dependent on the hippocampus and the amygdala, two brain centers that are prominently innervated by zinc-rich fibers. A common theme emerging from this research is the activity-dependent regulation of the Erk1/2 mitogen-activated-protein kinase pathway by synaptic zinc through diverse mechanisms in neurons. Here we discuss current knowledge on how synaptic zinc may play a role in cognition through its impact on neuronal signaling. PMID- 22084634 TI - Bilingualism and creativity: benefits in convergent thinking come with losses in divergent thinking. AB - Bilingualism is commonly assumed to improve creativity but the mechanisms underlying creative acts, and the way these mechanisms are affected by bilingualism, are not very well understood. We hypothesize that learning to master multiple languages drives individuals toward a relatively focused cognitive-control state that exerts strong top-down impact on information processing and creates strong local competition for selection between cognitive codes. Considering the control requirements posed by creativity tasks tapping into convergent and divergent thinking, this predicts that high-proficient bilinguals should outperform low-proficient bilinguals in convergent thinking, while low-proficient bilinguals might be better in divergent thinking. Comparing low- and high-proficient bilinguals on convergent-thinking and divergent-thinking tasks indeed showed a high-proficient bilingual advantage for convergent thinking but a low-proficient bilingual advantage for fluency in divergent thinking. These findings suggest that bilingualism should not be related to "creativity" as a unitary concept but, rather, to the specific processes and mechanisms that underlie creativity. PMID- 22084633 TI - Heart rate variability and non-linear dynamics in risk stratification. AB - The time-domain measures and power-spectral analysis of heart rate variability (HRV) are classic conventional methods to assess the complex regulatory system between autonomic nervous system and heart rate and are most widely used. There are abundant scientific data about the prognostic significance of the conventional measurements of HRV in patients with various conditions, particularly with myocardial infarction. Some studies have suggested that some newer measures describing non-linear dynamics of heart rate, such as fractal measures, may reveal prognostic information beyond that obtained by the conventional measures of HRV. An ideal risk indicator could specifically predict sudden arrhythmic death as the implantable cardioverter-defibrillator (ICD) therapy can prevent such events. There are numerically more sudden deaths among post-infarction patients with better preserved left ventricular function than in those with severe left ventricular dysfunction. Recent data support the concept that HRV measurements, when analyzed several weeks after acute myocardial infarction, predict life-threatening ventricular tachyarrhythmias in patients with moderately depressed left ventricular function. However, well-designed prospective randomized studies are needed to evaluate whether the ICD therapy based on the assessment of HRV alone or with other risk indicators improves the patients' prognosis. Several issues, such as the optimal target population, optimal timing of HRV measurements, optimal methods of HRV analysis, and optimal cutpoints for different HRV parameters, need clarification before the HRV analysis can be a widespread clinical tool in risk stratification. PMID- 22084632 TI - Neurotoxins and their binding areas on voltage-gated sodium channels. AB - Voltage-gated sodium channels (VGSCs) are large transmembrane proteins that conduct sodium ions across the membrane and by doing so they generate signals of communication between many kinds of tissues. They are responsible for the generation and propagation of action potentials in excitable cells, in close collaboration with other channels like potassium channels. Therefore, genetic defects in sodium channel genes can cause a wide variety of diseases, generally called "channelopathies." The first insights into the mechanism of action potentials and the involvement of sodium channels originated from Hodgkin and Huxley for which they were awarded the Nobel Prize in 1963. These concepts still form the basis for understanding the function of VGSCs. When VGSCs sense a sufficient change in membrane potential, they are activated and consequently generate a massive influx of sodium ions. Immediately after, channels will start to inactivate and currents decrease. In the inactivated state, channels stay refractory for new stimuli and they must return to the closed state before being susceptible to a new depolarization. On the other hand, studies with neurotoxins like tetrodotoxin (TTX) and saxitoxin (STX) also contributed largely to our today's understanding of the structure and function of ion channels and of VGSCs specifically. Moreover, neurotoxins acting on ion channels turned out to be valuable lead compounds in the development of new drugs for the enormous range of diseases in which ion channels are involved. A recent example of a synthetic neurotoxin that made it to the market is ziconotide (Prialt((r)), Elan). The original peptide, omega-MVIIA, is derived from the cone snail Conus magus and now FDA/EMA-approved for the management of severe chronic pain by blocking the N-type voltage-gated calcium channels in pain fibers. This review focuses on the current status of research on neurotoxins acting on VGSC, their contribution to further unravel the structure and function of VGSC and their potential as novel lead compounds in drug development. PMID- 22084635 TI - Cultural differences in affect intensity perception in the context of advertising. AB - Cultural differences in the perception of positive affect intensity within an advertising context were investigated among American, Japanese, and Russian participants. Participants were asked to rate the intensity of facial expressions of positive emotions, which displayed either subtle, low intensity, or salient, high intensity expressions of positive affect. In agreement with previous findings from cross-cultural psychological research, current results demonstrate both cross-cultural agreement and differences in the perception of positive affect intensity across the three cultures. Specifically, American participants perceived high arousal (HA) images as significantly less calm than participants from the other two cultures, while the Japanese participants perceived low arousal (LA) images as significantly more excited than participants from the other cultures. The underlying mechanisms of these cultural differences were further investigated through difference scores that probed for cultural differences in perception and categorization of positive emotions. Findings indicate that rating differences are due to (1) perceptual differences in the extent to which HA images were discriminated from LA images, and (2) categorization differences in the extent to which facial expressions were grouped into affect intensity categories. Specifically, American participants revealed significantly higher perceptual differentiation between arousal levels of facial expressions in high and intermediate intensity categories. Japanese participants, on the other hand, did not discriminate between high and low arousal affect categories to the same extent as did the American and Russian participants. These findings indicate the presence of cultural differences in underlying decoding mechanisms of facial expressions of positive affect intensity. Implications of these results for global advertising are discussed. PMID- 22084636 TI - Monetary Incentives Improve Performance, Sometimes: Speed and Accuracy Matter, and so Might Preparation. PMID- 22084638 TI - Larger Error Signals in Major Depression are Associated with Better Avoidance Learning. AB - The medial prefrontal cortex (mPFC) is particularly reactive to signals of error, punishment, and conflict in the service of behavioral adaptation and it is consistently implicated in the etiology of major depressive disorder (MDD). This association makes conceptual sense, given that MDD has been associated with hyper reactivity in neural systems associated with punishment processing. Yet in practice, depression-related variance in measures of mPFC functioning often fails to relate to performance. For example, neuroelectric reflections of mediofrontal error signals are often found to be larger in MDD, but a deficit in post-error performance suggests that these error signals are not being used to rapidly adapt behavior. Thus, it remains unknown if depression-related variance in error signals reflects a meaningful alteration in the use of error or punishment information. However, larger mediofrontal error signals have also been related to another behavioral tendency: increased accuracy in avoidance learning. The integrity of this error-avoidance system remains untested in MDD. In this study, EEG was recorded as 21 symptomatic, drug-free participants with current or past MDD and 24 control participants performed a probabilistic reinforcement learning task. Depressed participants had larger mid-frontal EEG responses to error feedback than controls. The direct relationship between error signal amplitudes and avoidance learning accuracy was replicated. Crucially, this relationship was stronger in depressed participants for high conflict "lose-lose" situations, demonstrating a selective alteration of avoidance learning. This investigation provided evidence that larger error signal amplitudes in depression are associated with increased avoidance learning, identifying a candidate mechanistic model for hypersensitivity to negative outcomes in depression. PMID- 22084637 TI - A potential role of the inferior frontal gyrus and anterior insula in cognitive control, brain rhythms, and event-related potentials. AB - IN THE PRESENT PAPER, WE REVIEW EVIDENCE FOR OF A MODEL IN WHICH THE INFERIOR FRONTAL GYRUS/ANTERIOR INSULA (IFG/AI) AREA IS INVOLVED IN ELABORATE ATTENTIONAL AND WORKING MEMORY PROCESSING AND WE PRESENT THE HYPOTHESIS THAT THIS PROCESSING MAY TAKE DIFFERENT FORMS AND MAY HAVE DIFFERENT EFFECTS, DEPENDING ON THE TASK AT HAND: (1) it may facilitate fast and accurate responding, or (2) it may cause slow responding when prolonged elaborate processing is required to increase accuracy of responding, or (3) it may interfere with accuracy and speed of next trial (for instance, post-error) performance when prolonged elaborate processing interferes with processing of the next stimulus. We present our viewpoint that ventrolateral corticolimbic control pathways, including the IFG/AI, and mediodorsal corticolimbic control pathways, including dorsal anterior cingulate cortex areas, play partly separable, but interacting roles in adaptive behavior in environmental conditions that differ in the level of predictability: compared to dorsal feed-forward control, the ventral corticolimbic control pathways implement control over actions through higher responsiveness to momentary environmental stimuli. This latter control mode is associated with an attentional focus on stimuli that are urgent or close in time and space, while the former control mode is associated with a broader, more global focus in time and space. Both control pathways have developed extensively through evolution, and both developed their own "cognitive controls," such that neither one can be properly described as purely "cognitive" or "emotional." We discuss literature that suggests that the role of IFG/AI in top-down control is reflected in cortical rhythms and event-related potentials. Together, the literature suggests that the IFG/AI is an important node in brain networks that control cognitive and emotional processing and behavior. PMID- 22084639 TI - Is the genetic landscape of the deep subsurface biosphere affected by viruses? AB - Viruses are powerful manipulators of microbial diversity, biogeochemistry, and evolution in the marine environment. Viruses can directly influence the genetic capabilities and the fitness of their hosts through the use of fitness factors and through horizontal gene transfer. However, the impact of viruses on microbial ecology and evolution is often overlooked in studies of the deep subsurface biosphere. Subsurface habitats connected to hydrothermal vent systems are characterized by constant fluid flux, dynamic environmental variability, and high microbial diversity. In such conditions, high adaptability would be an evolutionary asset, and the potential for frequent host-virus interactions would be high, increasing the likelihood that cellular hosts could acquire novel functions. Here, we review evidence supporting this hypothesis, including data indicating that microbial communities in subsurface hydrothermal fluids are exposed to a high rate of viral infection, as well as viral metagenomic data suggesting that the vent viral assemblage is particularly enriched in genes that facilitate horizontal gene transfer and host adaptability. Therefore, viruses are likely to play a crucial role in facilitating adaptability to the extreme conditions of these regions of the deep subsurface biosphere. We also discuss how these results might apply to other regions of the deep subsurface, where the nature of virus-host interactions would be altered, but possibly no less important, compared to more energetic hydrothermal systems. PMID- 22084640 TI - The potential for poly (ADP-ribose) polymerase inhibitors in cancer therapy. AB - The modulation of DNA repair pathways for therapeutic benefit in cancer has now become a reality with the development of poly (ADP-ribose) polymerase inhibitors (PARPi). PARP is involved in single-strand DNA breaks, which in the presence of defective homologous recombination repair lead to double-strand DNA breaks, the most lethal form of DNA damage. These agents therefore may be the drugs of choice for BRCA mutant breast and ovarian cancers. PARPi result in synergistic antitumor effects when combined with cisplatin, temozolomide, topoisomerase inhibitors and ionizing radiation. The indications for PARPi lie beyond BRCA mutations and may include genomic and functional defects in DNA repair and damage response pathways. Several PARPi are in the clinical development phase at this time and, given the recent failure of a phase III clinical trial of iniparib in triple negative breast cancer, the identification of structural and functional differences between these inhibitors becomes critical. Acquired resistance to PARPi is being noted and represents an important limitation in this field. A concise review of the literature in this field is presented. PMID- 22084641 TI - Preventing bowel cancer: an insight for clinicians. AB - Worldwide, colorectal cancer causes 610,000 deaths annually with 38,000 new cases diagnosed in the UK and 16,000 deaths each year. The prognosis is directly related to the staging of the cancer at diagnosis, with an overall 5-year survival rate of approximately 50%. However, for localized disease the figure is much higher at 90%, although unfortunately many cancers present at an advanced stage. Importantly, there is the potential to reduce the incidence because most tumours arise from premalignant adenomatous polyps, which if detected and removed interrupts the adenoma-adenocarcinoma sequence. In addition, identifying colorectal cancer at an early stage can impact on the mortality rates for this neoplasm. The current screening options for bowel cancer include analysis of stool for occult blood and endoscopic assessments of the colorectum, including flexible sigmoidoscopy and full colonoscopy. The aim of this review is to present information on the natural history of colorectal cancer, the evaluation of the different screening modalities and the current faecal occult blood screening program within the UK National Health Service, and to discuss how dietary factors and aspirin may affect aetiology. PMID- 22084642 TI - The potential for crizotinib in non-small cell lung cancer: a perspective review. AB - Tyrosine kinases have a crucial role as key regulators of signaling pathways that influence cell differentiation and growth. Dysregulation of tyrosine kinase mediated signaling is understood to be an important oncogenic driver. Genetic rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) gene occur in non-small cell lung cancer (NSCLC), anaplastic large cell lymphomoas, inflammatory myofibroblastic tumors, and other cancers. Cells with abnormal ALK signaling are sensitive to ALK inhibitors such as crizotinib. This review will highlight the discovery of the fusion between echinoderm microtubule associated protein-like 4 (EML4) and ALK as an oncogenic driver, recognition of other ALK gene rearrangements in NSCLC, and the confirmation that crizotinib is an effective treatment for patients with ALK-positive NSCLC. Work is underway to further define the role for crizotinib in the treatment of ALK-positive lung cancer and other cancers and to investigate the molecular mechanisms for resistance to ALK inhibition with crizotinib. PMID- 22084643 TI - Zoledronic acid in breast cancer: latest findings and interpretations. AB - The intravenous nitrogen-containing bisphosphonate zoledronic acid has been shown to block multiple steps in tumor metastasis (e.g. angiogenesis, invasion, adhesion, proliferation) in preclinical and translational studies. Moreover, clinical data from the ABCSG-12 and ZO-FAST trials demonstrate significantly improved disease-free survival with zoledronic acid in the adjuvant breast cancer setting. In contrast to these two trials, recent interim results from the AZURE trial do not show a benefit from adding zoledronic acid to adjuvant therapy in the overall patient population. However, subset analyses of AZURE data show that zoledronic acid significantly improved overall survival in women who were more than 5 years postmenopausal or older than 60 years at baseline. Similarly, subset analyses of the ABCSG-12 trial data demonstrate greater benefits from zoledronic acid treatment in patients who theoretically would have achieved more complete ovarian suppression. These observations, together with the AZURE postmenopausal data, suggest that the endocrine environment may affect the potential anticancer activity of zoledronic acid. Indeed, current data support the possibility that zoledronic acid might be most effective for improving disease-free survival in the adjuvant breast cancer setting in women who are postmenopausal or have endocrine therapy-induced menopause. PMID- 22084644 TI - Malignant melanoma in the elderly: different regional disease and poorer prognosis. AB - PURPOSE: Age is a poor prognostic factor in melanoma patients. Elderly melanoma patients have a different presentation and clinical course than younger patients. We evaluated the impact of age >=70 years (yrs) on the diagnosis and natural history of melanoma. METHODS: Retrospective review of 610 patients with malignant melanoma entered into a prospective sentinel lymph node (SLN) database, treated from June 1997 to June 2010. Disease characteristics and clinical outcomes were compared between patients >=70 yrs vs. <70 yrs of age. RESULTS: 237 patients (39%) were >=70 yrs. Elderly patients had a higher proportion of head and neck melanomas (34% vs. 20%, p<0.001), and greater mean tumor thickness (2.4mm vs. 1.8mm, p<0.001). A greater proportion of T3 or T4 melanoma was seen in the elderly (p<0.001) as well as a greater mean number of mitotic figures: 3.6/mm(2) vs. 2.7/mm(2) (p=0.005). Despite greater mean thickness, the incidence of SLN metastases was less in the >=70 yrs group with T3/T4 melanomas (18% vs. 33%, p=0.02). The elderly had a higher rate of local and in-transit recurrences, 14.5% vs. 3.4% at 5 yrs (p<0.001). 5 yr disease-specific mortality and overall mortality were worse for those >=70 yrs: 16% vs. 8% (p=0.004), and 30% vs. 12% (p<0.001), respectively. CONCLUSIONS: Elderly (>=70 yrs) melanoma patients present with thicker melanomas and a higher mitotic rate but have fewer SLN metastases. Melanoma in the elderly is more common on the head and neck. Higher incidence of local/in-transit metastases is seen among the elderly. Five-year disease-specific mortality and overall mortality are both worse for these patients. PMID- 22084645 TI - Complications following expander/implant breast reconstruction utilizing acellular dermal matrix: a systematic review and meta-analysis. AB - BACKGROUND: The recent increase in popularity of acellular dermal matrix assistance in immediate expander/implant breast reconstruction has led to variety of viewpoints. Many studies are published indicating an increase in complications with the use of acellular dermal matrix, while others indicate there is no increase in complications. METHODS: This meta-analysis utilizes information from available studies that directly compare one specific type of acellular dermal matrix with traditional methods of immediate expander/implant breast reconstruction. Eight studies were found through a meticulous literature search that met these criteria. RESULTS: There was more than a 2-fold increase in the number of infections and explanations in the acellular dermal matrix group compared to the control. There was a 3-fold increase in seroma formation in the acellular dermal matrix group compared to the control. There was a significant difference of intraoperative fill volumes between the acellular dermal matrix group compared to the control. CONCLUSIONS: This study illustrates that after pooling all available date regarding the use of acellular dermal matrix in immediate expander/implant breast reconstruction there appears to be an increased rate of complications. However, the increased intraoperative fill volume may lead to ultimately greater patient satisfaction. PMID- 22084647 TI - Quality control for diagnostic oral microbiology laboratories in European countries. AB - Participation in diagnostic microbiology internal and external quality control (QC) processes is good laboratory practice and an essential component of a quality management system. However, no QC scheme for diagnostic oral microbiology existed until 2009 when the Clinical Oral Microbiology (COMB) Network was created. At the European Oral Microbiology Workshop in 2008, 12 laboratories processing clinical oral microbiological samples were identified. All these were recruited to participate into the study and six laboratories from six European countries completed both the online survey and the first QC round. Three additional laboratories participated in the second round. Based on the survey, European oral microbiology laboratories process a significant (mean per laboratory 4,135) number of diagnostic samples from the oral cavity annually. A majority of the laboratories did not participate in any internal or external QC programme and nearly half of the laboratories did not have standard operating procedures for the tests they performed. In both QC rounds, there was a large variation in the results, interpretation and reporting of antibiotic susceptibility testing among the laboratories. In conclusion, the results of this study demonstrate the need for harmonisation of laboratory processing methods and interpretation of results for oral microbiology specimens. The QC rounds highlighted the value of external QC in evaluating the efficacy and safety of processes, materials and methods used in the laboratory. The use of standardised methods is also a prerequisite for multi-centre epidemiological studies that can provide important information on emerging microbes and trends in anti-microbial susceptibility for empirical prescribing in oro-facial infections. PMID- 22084648 TI - Treatment of Acute Promyelocytic Leukemia with AIDA Based Regimen. Update of a Tunisian Single Center Study. AB - In Tunisia, the ATRA era began in 1998 with the use, consecutively, of two regimens combining ATRA and an anthracycline with cytarabine (APL93), and without cytarabine (LPA99). From 2004, 51 patients with confirmed APL either by t(15;17) or PML/RARA were treated according to the PETHEMA LPA 99 trial. Forty three patients achieved CR (86%). The remaining seven patients had early death (one died before treatment onset): four caused by differentiation syndrome (DS) and three died from central nervous system hemorrhage. Multivariate analysis revealed that female gender (P=0.045), baseline WBC> 10 G/L (P=0.041) and serum creatinine > 1.4mg/dl (P=0.021) were predictive of mortality during induction. DS was observed in 16 patients (32%) after a median onset time of 15 days from treatment onset (range, 2-29). Body mass index >= 30 (P=0.01) remained independent predictor of DS. Occurrence of hypertensive peaks significantly predicted occurrence of DS (P=0.011) and was significantly associated with high BMI (p=0.003). With a median follow-up of 50 months, 5 year cumulative incidence of relapse, event free and overall survival were 4.7%, 74% and 78%, respectively. PMID- 22084649 TI - ATRA Induced Reactive Hemophagocytosis: a Case Report. AB - All trans-retinoic acid (ATRA) is a targeted therapy, used in Acute Promyelcytic leukemia (APL) and causes the abnormal promyelocytes to differentiate in to mature leucocytes, however their clearance in vivo is not known. ATRA has been found to be associated with hemophagocytosis, but sometimes one may find phagocytosis of differentiated cells by histiocytes without the overt manifestations of hemophagocytic syndrome. We report a case of APL showing differentiated cells being phagocytosed by marrow histiocytes while patient was getting ATRA therapy. PMID- 22084646 TI - The use of growth factors and other humoral agents to accelerate and enhance burn wound healing. AB - OBJECTIVE: Certain cytokines, especially those known as growth factors, have been demonstrated to mediate or modulate burn wound healing. Experimental and clinical evidence suggests that there are therapeutic advantages to the wound healing process when these agents are utilized. Positive effects have been reported for 4 types of wounds seen in the burn patient: partial-thickness wounds, full thickness wounds, interstices of meshed skin grafts, and skin graft donor sites. METHODS: A comprehensive literature search was performed using the MEDLINE, Ovid, and Web of Science databases to identify pertinent articles regarding growth factors and other cytokines in burns and wound healing. RESULTS: The current knowledge about cytokine growth factors and their potential therapeutic applications in burn wound healing are discussed and reviewed. CONCLUSIONS: Platelet-derived growth factor, fibroblast growth factors, epidermal growth factors, transforming growth factor alpha, vascular endothelial growth factor, insulin-like growth factor I, nerve growth factor, transforming growth factor beta, granulocyte-macrophage colony-stimulating factor, and amnion-derived cellular cytokine solution have all been suggested to enhance the rate and quality of healing in 1 or more of these wounds encountered in burn care. PMID- 22084650 TI - A case series highlighting the relative frequencies of the common, uncommon and atypical/unusual hematological findings on bone marrow examination in cases of visceral leishmaniasis. AB - INTRODUCTION: Bone marrow aspiration and biopsy still remains as one of the vital tests for confirmation of diagnosis of visceral Leishmaniasis. The aim of the present study is to assess the relative frequency of common, uncommon and atypical hematological findings in cases of Visceral Leishmaniasis. MATERIALS #ENTITYSTARTX00026; METHODS: A total of 16 cases of Leishmaniasis diagnosed on Bone marrow examination over a period of two years (2008-2010), were retrieved from the archives and the peripheral blood smear, bone marrow aspiration smears and trephine biopsies were examined for the common, uncommon and atypical features as described in the literature. RESULTS: Out of the total of 16 cases, 10 were pediatric and 6 adult cases. The common findings like pancytopenia, peripheral blood monocytosis, increased histiocytes on aspirate smears and granulomas on biopsies were noted in 12/16 (75%), 9/16 (56.25%), 13/16 (81.2%) and 11/16 (69%) cases respectively. Amongst the uncommon findings, hemophagocytosis was noted in 12/16 (75%) cases, plasma cells with inclusions in 6/16 (37.5%) and LD bodies in cells other than histiocytes in 4/16 (25%) cases. The atypical findings included organism aggregates noted in 9/16 (56%) cases, Pelger-Heut cells seen in 4/16 (25%) cases and increased focal vascularity on biopsies in 10/16 (62.5%) cases. The average parasite density (APD) on smears was 3+ and the range of positivity was 1+ to 5+. CONCLUSION: The knowledge of these morphological clues can assist us in searching for LD bodies and correctly diagnosing the condition without excessive dependence on unnecessary and sophisticated tests. PMID- 22084651 TI - Coexisting pulmonary tuberculosis and mucormycosis in a patient with aplastic anemia post allogenic stem cell transplantation. AB - Infections are the most common cause of morbidity and mortality in allogenic stem cell transplant recipients. Survival of the patient depends on the accurate diagnosis of the infectious agents and prompt and effective management of the infection alongwith maintenance of adequate immunosuppression post transplantation. We here reported a case of aplastic anemia who developed left upper lobe consolidation post allogenic stem cell transplantation and was found to have combined infection with tuberculosis and mucormycosis. This is the first case of combined infection with tuberculosis and mucormycosis reported in such a host, with a favourable outcome. PMID- 22084653 TI - Clinical profile of dengue infection in patients with hematological diseases. AB - Managing hematological disorders in a tropical country presents several unique diagnostic and management problems. Apart from the disease process, we need to be aware of infections that can exacerbate or mimic serious hematological problems. We present here a series of five patients with pre-existing hematological diseases who were infected by dengue virus. These cases highlight the need to keep a strong suspicion of common endemic diseases in tropical countries before considering extensive workup for the basic hematological disease. There was no mortality and all patients recovered without any significant impact on their pre existing hematological condition inspite of their low baseline blood counts. There was no excessive bleeding, prolonged stay in the hospital or relapse of underlying hematological disease in these patients and the only major concern was the increased anxiety among both the patient and treating physician regarding the relapse/progression of pre-existing hematological disease. PMID- 22084652 TI - Treatment of acute promyelocytic leukemia with high white cell blood counts. AB - Acute promyelocytic leukemia (APL) with WBC above 10 G/L has long been considered, even in the all-trans retinoic acid (ATRA) era, to carry a relatively poor prognosis (compared to APL with WBC below 10 G/L), due to increased early mortality and relapse. However, early deaths can to a large extent be avoided if specific measures are rapidly instigated, including prompt referral to a specialized center, immediate onset of ATRA and chemotherapy, treatment of coagulopathy with adequate platelet transfusional support, and prevention and management of differentiation syndrome. Strategies to reduce relapse rate include chemotherapy reinforcement with cytarabine and/or arsenic trioxide during consolidation, prolonged maintenance treatment, especially with ATRA and low dose chemotherapy, and possibly, although this is debated, intrathecal prophylaxis to prevent central nervous system relapse. By applying those measures, outcomes of patients with high risk APL have considerably improved, and have become in many studies almost similar to those of standard risk APL patients. PMID- 22084654 TI - Takayasu arteritis initially mimicking infective endocarditis. AB - Takayasu's arteritis (TA) is a chronic inflammatory disease that affects large vessels, predominantly the aorta and its main branches, leading to vessel wall thickening, fibrosis and stenosis. Cardiac and vascular symptoms are also commonly present at disease onset. In TA with thoracic or abdominal involvement, although murmur can be present at physical examination, the pulse difference may be absent. Here, we report a case of TA who initially resembled infective endocarditis and had widespread thoracic murmur. PMID- 22084655 TI - Possible clinical failure of artemether-lumefantrine in an italian traveler with uncomplicated falciparum malaria. AB - Artemisinin-combination therapies (ACTs) are recommended for the treatment of uncomplicated malaria in endemic areas with multidrug resistant Plasmodium falciparum. We report a case of possible artemether-lumefantrine clinical failure in an Italian traveler with uncomplicated P. falciparum malaria imported from Democratic Republic of Congo. PMID- 22084656 TI - Cauda Equina Enhancing Lesion in an HIV-Infected Patient. Case Report and Literature Review. AB - We report the case of an HIV-infected young men with neuro-toxoplasmosis localized in the spinal cord. The patient received chemotherapy and immunotherapy for Burkitt lymphoma one year before. At the time of the diagnosis of toxoplasmosis, he was on prophylaxis with trimethoprim and sulfamethoxazole and in complete remission of Burkitt lymphoma. The CD4+ T cell count was 270/MUl and the HIV viremia was undetectable. These findings suggest that in this patient, the immunodeficiency promoting the neurologic toxoplasmosis arose more from previous immuno-chemotherapy than from the HIV-infection itself. On the whole, this case highlights that the risk stratification for opportunistic infections of HIV-infected patients should carefully consider their previous medical history and therapies received. PMID- 22084657 TI - Simplifying thromboprophylaxis could improve outcomes in orthopaedic surgery. AB - Venous thromboembolism is a serious complication after total hip or knee surgery, and there is a well-established clinical need for thromboprophylaxis. However, in a large number of cases adequate administration of thromboprophylaxis does not seem to occur after total joint arthroplasty. A major challenge in the management of thromboprophylaxis is to balance the benefits of treatment with the risks, including bleeding complications. Another potential barrier to the optimal use of thromboprophylaxis could be the inconvenience of currently available agents. Many surgeons therefore adopt a conservative approach towards thromboprophylaxis. Simplifying therapy with more convenient, efficacious, and safe anticoagulants could change attitudes to anticoagulant use and improve adherence to thromboprophylactic guidelines. PMID- 22084658 TI - New oral anticoagulants for thromboprophylaxis after elective total hip and knee arthroplasty. AB - Anticoagulant drugs reduce the risk of venous thromboembolic events after total hip and knee arthroplasty. However, the use of current drugs, such as low molecular weight heparins, is hampered by their subcutaneous route of administration. The use of vitamin K antagonists is hampered by the requirement for routine coagulation monitoring and dose titration to provide effective anticoagulation without an increased risk of bleeding and numerous food and drug interactions. Clearly, there is a need for new oral, fixed-dose anticoagulant drugs that do not require coagulation monitoring, while demonstrating similar or better efficacy and safety profiles when compared with current agents. PMID- 22084659 TI - Thrombin a-chain: activation remnant or allosteric effector? AB - Although prothrombin is one of the most widely studied enzymes in biology, the role of the thrombin A-chain has been neglected in comparison to the other domains. This paper summarizes the current data on the prothrombin catalytic domain A-chain region and the subsequent thrombin A-chain. Attention is given to biochemical characterization of naturally occurring prothrombin A-chain mutations and alanine scanning mutants in this region. While originally considered to be simply an activation remnant with little physiologic function, the thrombin A chain is now thought to play a role as an allosteric effector in enzymatic reactions and may also be a structural scaffold to stabilize the protease domain. PMID- 22084660 TI - Different Finite Durations of Anticoagulation and Outcomes following Idiopathic Venous Thromboembolism: A Meta-Analysis. AB - Introduction. Controversy remains over the optimal length of anticoagulation following idiopathic venous thromboembolism. We sought to determine if a longer, finite course of anticoagulation offered additional benefit over a short course in the initial treatment of the first episode of idiopathic venous thromboembolism. Data Extraction. Rates of deep venous thrombosis, pulmonary embolism, combined venous thromboembolism, major bleeding, and mortality were extracted from prospective trials enrolling patients with first time, idiopathic venous thromboembolism. Data was pooled using random effects meta-regression. Results. Ten trials, with a total of 3225 patients, met inclusion criteria. For each additional month of initial anticoagulation, once therapy was stopped, recurrent venous thromboembolism (0.03 (95% CI: -0.28 to 0.35); P = .24), mortality (-0.10 (95% CI: -0.24 to 0.04); P = .15), and major bleeding (-0.01 (95% CI: -0.05 to 0.02); P = .44) rates measured in percent per patient years, did not significantly change. CONCLUSIONS: Patients with an initial idiopathic venous thromboembolism should be treated with 3 to 6 months of secondary prophylaxis with vitamin K antagonists. At that time, a decision between continuing with indefinite therapy can be made, but there is no benefit to a longer (but finite) course of therapy. PMID- 22084661 TI - The Potential Value of Near Patient Platelet Function Testing in PCI: Randomised Comparison of 600 mg versus 900 mg Clopidogrel Loading Doses. AB - Whilst poor response to clopidogrel is associated with adverse outcomes uncertainty exists as to how (a) response should be assessed and (b) poor responders managed. We utilised VerifyNow P2Y12 and short Thrombelastography (TEG) to assess 900 mg doses in (i) initial poor responders to 600 mg and (ii) in a randomised comparison with 600 mg. Blood was taken before and six hours post clopidogrel in (i) 30 volunteers receiving 600 mg (poor responders received 900 mg > two weeks later) and (ii) 60 patients randomized 1 : 1 to 600 mg or 900 mg doses. Poor response was defined as TEG %Clotting Inhibition (%CIn) or VerifyNow Platelet Response Unit (PRU) reduction <30%. (i) Poor responders to 600 mg had greater PRU reduction (45.0 versus 20.1%, P = 0.03) and greater %CIn (22.9 versus -15.1%, P = 0.01) after 900 mg but (ii) there were no significant differences between the patient groups. Near-patient assessment of response to clopidogrel is feasible and clinically useful. Whilst ineffective on a population basis 900 mg doses increase the effect of clopidogrel in initial poor responders. PMID- 22084662 TI - Urinary Prothrombin Fragment 1+2 in relation to Development of Non-Symptomatic and Symptomatic Venous Thromboembolic Events following Total Knee Replacement. AB - Prothrombin fragment 1+2 is excreted in urine (uF1+2) as a result of in vivo thrombin generation and can be a marker of coagulation status after an operative procedure. This study compared uF1+2 levels in patients with symptomatic and non symptomatic venous thromboembolism (VTE) after total knee replacement (TKR) and in event-free sex- and age-matched controls. Significantly higher median uF1+2 levels were seen in the VTE patients on days 1, 3, and the day of venography (mostly day 7) after TKR compared with controls. The uF1+2 levels tended to be high in some patients with symptomatic VTE; however, the discriminatory efficacy of the test could not be evaluated. In conclusion, this study showed that patients with VTE tend to have significantly higher uF1+2 levels compared with patients without events between days 1 and 7 after TKR surgery. Measurement of uF1+2 could provide a simple, non-invasive clinical test to identify patients at risk of VTE. PMID- 22084663 TI - Deep vein thrombosis prophylaxis in trauma patients. AB - Deep vein thrombosis (DVT) and pulmonary embolism (PE) are known collectively as venous thromboembolism (VTE). Venous thromboembolic events are common and potentially life-threatening complications following trauma with an incidence of 5 to 63%. DVT prophylaxis is essential in the management of trauma patients. Currently, the optimal VTE prophylaxis strategy for trauma patients is unknown. Traditionally, pelvic and lower extremity fractures, head injury, and prolonged immobilization have been considered risk factors for VTE; however it is unclear which combination of risk factors defines a high-risk group. Modalities available for trauma patient thromboprophylaxis are classified into pharmacologic anticoagulation, mechanical prophylaxis, and inferior vena cava (IVC) filters. The available pharmacologic agents include low-dose heparin (LDH), low molecular weight heparin (LMWH), and factor Xa inhibitors. Mechanical prophylaxis methods include graduated compression stockings (GCSs), pneumatic compression devices (PCDs), and A-V foot pumps. IVCs are traditionally used in high risk patients in whom pharmacological prophylaxis is contraindicated. Both EAST and ACCP guidelines recommend primary use of LMWHs in trauma patients; however there are still controversies regarding the definitive VTE prophylaxis in trauma patients. Large randomized prospective clinical studies would be required to provide level I evidence to define the optimal VTE prophylaxis in trauma patients. PMID- 22084664 TI - Clinical use of the low-molecular-weight heparins in cancer patients: focus on the improved patient outcomes. AB - Patients with malignant neoplastic diseases represent a high-risk population relative to thromboembolic disease. With the advent of improved and accessible diagnostic technology, for example, ultrasound and/or spiral CT scans, timely diagnosis of venous thromboembolic events (VTE) is readily accomplished. The introduction of low-molecular-weight heparin (LMWH) approximately two decades ago (in contrast to unfractionated heparin and vitamin K antagonists) has provided a class of agents with a favorable therapeutic index. In the review to follow, the literature regarding the use of LMWH in oncologic patient populations is summarized. Topics addressed include prophylaxis, and treatment as well as consideration of the potential anti-neoplastic properties of this class of drugs. PMID- 22084666 TI - Incidence of Deep Vein Thrombosis in Hospitalized Chinese Medical Patients and the Impact of DVT Prophylaxis. AB - Objective. To evaluate the incidence of deep vein thrombosis in hospitalized Chinese medical patients and the impact of DVT prophylaxis. Methods. All cases of confirmed proximal DVT from 1 January 2005 to 31 December 2008 were reviewed retrospectively to determine the presence of risk factors and whether DVT developed: during hospitalization in medical wards or in case of readmission with a diagnosis of DVT within 14 days of discharge from a recent admission to medical wards. The impact of prophylaxis will be estimated by comparing the annual incidence of proximal DVT among medical patients hospitalized from 2005 to 2007 with that of 2008 (DVT prophylaxis commonly used). Results. From 1 January 2005 to 31 December 2008, 3938 Doppler ultrasound studies were performed for suspected DVT. Proximal DVT was diagnosed in 687 patients. The calculated incidence of proximal DVT among medical patients hospitalized for at least two days was 1.8%, 2%, and 1.7% for the year 2005, 2006, and 2007, respectively. The incidence was 1.1% for 2008 (P < .001). Conclusion. Proximal DVT was substantial in Chinese medical patients, and DVT prophylaxis might reduce such risk. PMID- 22084665 TI - Thrombocytosis: diagnostic evaluation, thrombotic risk stratification, and risk based management strategies. AB - Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID- 22084667 TI - The use of a scoring system to guide thromboprophylaxis in a high-risk pregnant population. AB - Guidelines for thromboprophylaxis in pregnancy are usually based upon clinical observations and expert opinion. For optimal impact, their use must be attended by consistency in the advice given to women. In this observational study, we evaluated the performance of a scoring system, used as a guide for clinicians administering dalteparin to pregnant women at increased risk of venous thromboembolism. The work included 47 women treated with dalteparin prior to adoption of the scoring system and 58 women treated with dalteparin after its adoption. The indication for thromboprophylaxis was recorded in each case together with details of the regimen employed, obstetric, and haematological outcomes. The main outcome measure was to determine whether consistency improved after adoption of the scoring system. We also recorded the occurrence of any new venous thromboembolism, haemorrhage, the use of regional anaesthesia during labour, evidence of allergy, and thrombocytopenia. We found that use of the scoring system improved the consistency of advice and increased the mean duration of thromboprophylaxis. None of the subjects suffered venous thromboembolism after assessment using the scoring system. There was no increase in obstetric or anaesthetic morbidity when dalteparin was given antenatally period and no evidence of heparin-induced thrombocytopenia. PMID- 22084668 TI - The CYTO-PV: A Large-Scale Trial Testing the Intensity of CYTOreductive Therapy to Prevent Cardiovascular Events in Patients with Polycythemia Vera. AB - Polycythemia vera (PV) is a chronic myeloproliferative disorder whose major morbidity and mortality are thrombohaemorragic events. Current guidelines advise maintaining hematocrit (HCT) level below 45% in males and 42% in females. Such targets lean on pathophysiological reasoning, while evidence from ECLAP and PVSG 01, the two largest prospective studies in this disease, suggests no difference in the rate of thrombosis in patients maintained at different HCT values below 50%-52%. Cytoreductive therapy in PV (CYTO-PV) is a multicenter, randomized, and controlled trial assess the benefit/risk profile of cytoreductive therapy with phlebotomy or HU aimed at maintaining HCT < 45% versus maintaining HCT in the range 45%-50%. CYTO-PV is being conducted in the framework of the Gruppo Italiano Malattie Ematologiche nell'Adulto (GIMEMA) and is funded by the Italian Drug Agency (AIFA). It is an independent trial with broad recruitment criteria to mimic clinical practice. We describe here the study and its advancement status. Conclusions. Clinical research in rare disease can be carried out with limited funds, provided a research hypothesis is felt as clinically relevant by a scientific community willing to share knowledge on the outcome of clinical practice, thus producing scientific results useful to improve treatment and prognosis of patients. PMID- 22084669 TI - Venous thromboembolism following colorectal surgery for suspected or confirmed malignancy. AB - Surgery for colorectal cancer conveys a high risk of venous thromboembolism (VTE). The effect of thromboprophylactic regimens of varying duration on the incidence of VTE was assessed in 417 patients undergoing surgery between 2005 and 2009 for colorectal cancer. Low-dose unfractionated heparin (LDUH) was used in 52.7% of patients, low-molecular-weight heparin (LMWH) in 35.3%, and 10.7% received LDUH followed by LMWH. Pharmacological prophylaxis was continued after hospitalisation in 31.6%. Major bleeding occurred in 4% of patients. The 30-day mortality rate was 1.9%. The incidence of symptomatic VTE from hospital admission for surgery to 12 months after was 2.4%. There were no in-hospital VTE events. The majority of events occurred in the three-month period after discharge, but there were VTE events up to 12 months, especially in patients with more advanced cancer and multiple comorbidities. PMID- 22084670 TI - Gender and Vascular Complications in the JAK2 V617F-Positive Myeloproliferative Neoplasms. AB - We previously found that gender influenced the JAK2 V617F allele burden, but it is unknown whether this gender difference in molecular epidemiology influences complications in the myeloproliferative neoplasms (MPNs). Historically, vascular complications represented the most common cause of mortality in polycythemia vera and essential thrombocytosis and contributed to morbidity in primary myelofibrosis. To determine the influence of gender on vascular complications, we retrospectively analyzed associations between gender and vascular complications. Despite their younger age, less prevalent dyslipidemia or smoking history, lower white blood counts, and lower JAK2 V617F allele burden, women had higher rates of abdominal venous thrombosis and comparable rates of all vascular complications. Vascular risk is currently not easily stratified by MPN-disease burden or traditional risk factors. Our analysis contributes to growing literature emphasizing gender differences in the MPN and further supports the important impact of individual and host variation on MPN clinical manifestations, and especially vascular risk. PMID- 22084671 TI - Emergency Physician Performed Ultrasound for DVT Evaluation. AB - Deep vein thrombosis is a common condition that is often difficult to diagnose and may be lethal when allowed to progress. However, early implementation of treatment substantially improves the disease prognosis. Therefore, care must be taken to both acquire an accurate differential diagnosis for patients with symptoms as well as to screen at-risk asymptomatic individuals. Many diagnostic tools exist to evaluate deep vein thrombosis. Compression ultrasonography is currently the most effective diagnostic tool in the emergency department, shown to be highly accurate at minimal expense. However, limited availability of ultrasound technicians may result in delayed imaging or in a decision not to image low-risk cases. Many studies support emergency physiciansas capable of accurately diagnosing deep vein thrombosis using bedside ultrasound. Further integration of ultrasound into the training of emergency physicians for use in evaluating deep vein thrombosis will improve patient care and cost-effective treatment. PMID- 22084672 TI - Treatment of Deep Vein Thrombosis with Continuous IV Infusion of LMWH: A Retrospective Study in 32 Children. AB - Thirty-two consecutive children aged 0-18 years with VTE treated with LMWH administered as a continuous infusion (CI) were identified at the Children's University Hospital Brno. The treatment led to at least partial resolution of the thrombus within two weeks in 85% of patients. There were no adverse events or increased bleeding reported in any patients. No recurrences were observed during a followup period of 6 months. Although continuous infusion should not replace subcutaneous (SC) administration of LMWH, CI appeared to be safe and efficient and may provide an alternate method of administering LMWH in a subset of the paediatric population where SC administration may not be feasible. Further prospective studies are needed to support the promising findings of our pilot clinical observation. PMID- 22084673 TI - Are we missing post-thrombotic syndrome syndrome? An orthopaedic perspective in lower limb arthroplasty. AB - 2-5% of patients undergoing hip or knee arthroplasty develop a symptomatic DVT; there is evidence to suggest that without prophylaxis 40-60% of patients have a subclinical DVT. This can be reduced by around half with appropriate thromboprophylaxis; there still remains a significant incidence of subclinical DVT. Therefore, it is important to know, as orthopaedic surgeons, if our patients undergoing large joint arthroplasty are being adversely affected. Post-thrombotic syndrome (PTS) is usually associated with symptomatic DVT, and the purpose of this paper is to address if asymptomatic DVT is also associated with an increased risk of PTS. The majority of evidence gathered does not support a link; therefore, there is no evidence to warrant a change in practice to warn patients of a potential risk or to routinely screen asymptomatic patients. PMID- 22084674 TI - Postthrombotic syndrome: surgical possibilities. AB - Postthrombotic syndrome (PTS) is a late outcome of deep vein thrombosis characterized by cramping pain, swelling, hyperpigmentation, eczema, lipodermatosclerosis, and ulceration in the leg due to increased venous outflow resistance and reflux venous flow. Newer surgical and endovascular interventions have a promising result in the management of postthrombotic syndrome. Early surgical or endovascular interventions in appropriately selected patients may decrease the incidence of recurrent ulceration and skin changes and provide a better quality of life. Duplex and IVUS (intravenous ultrasound) along with venography serve as cornerstone investigative tools for assessment of reflux and obstruction. Venous obstruction, if present, should be addressed earlier than reflux. It requires endovenous stenting, endophlebectomy, or open bypass procedures. Venous stripping, foam sclerotherapy, radiofrequency, or laser ablation are used to abolish superficial venous reflux. Valvuloplasty procedures are useful for incompetent but intact deep venous valves, while transposition or axillary vein autotransplantation is done for completely destroyed valves. PMID- 22084675 TI - Heat shock protein: hard worker or bad offender for gastric diseases. AB - Heat shock proteins (HSPs) have core housekeeping functions in the cells where they are built-in components of folding, signal transduction pathways, and quality control functions for which they proofread the structure of proteins and repair misfolded conformers. Helicobacter pylori (H. pylori) infection leads to significant inflammations in the gastric mucosa, which is closely associated with development of either precancerous lesion including chronic atrophic gastritis or gastric cancer in addition to, peptic ulcer disease, and mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, the association between H. pylori infection and role of HSP has been focused as an important issue because there had been rather conflicting publications showing that HSPs as a good worker for defense against H. pylori infection, whereas HSPs as a bad offender contributing to the progression of H. pylori-associated gastric carcinogenesis in addition to aggravation of gastric inflammation. In this paper regarding proteomic discovery of HSPs related to H. pylori-associated gastric diseases, we introduce several evidences obtained from proteomic analysis dealing with friend or foe role of HSP in H. pylori infection from a cellular level to human diseases. The implication of HSPs in alcoholic or NSAIDs-induced gastritis and the intervening of HSPs in biological changes exemplified with TGF-beta signaling, key tumor suppressor growth factors regulating inflammation, immune function, and carcinogenesis were further introduced. PMID- 22084676 TI - p73-Binding Partners and Their Functional Significance. AB - p73 is one of the tumor-suppressor p53 family of nuclear transcription factor. As expected from the structural similarity between p53 and p73, p73 has a tumor suppressive function. However, p73 was rarely mutated in human primary tumors. Under normal physiological conditions, p73 is kept at an extremely low level to allow cells normal growth. In response to a certain subset of DNA damages, p73 is induced dramatically and transactivates an overlapping set of p53-target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death. Cells undergo cell cycle arrest and/or apoptotic cell death depending on the type and strength of DNA damages. p73 is regulated largely through the posttranslational modifications such as phosphorylation and acetylation. These chemical modifications are tightly linked to direct protein-protein interactions. In the present paper, the authors describe the functional significance of the protein-protein interactions in the regulation of proapoptotic p73. PMID- 22084677 TI - Heat shock proteins in the human eye. AB - Heat shock proteins (Hsps) are believed to primarily protect and maintain cell viability under stressful conditions such as those occurring during thermal and oxidative challenges chiefly by refolding and stabilizing proteins. Hsps are found throughout the various tissues of the eye where they are thought to confer protection from disease states such as cataract, glaucoma, and cancer. This minireview summarizes the placement, properties, and roles of Hsps in the eye and aims to provide a better comprehension of their function and involvement in ocular disease pathogenesis. PMID- 22084678 TI - Proteomic Signatures of the Zebrafish (Danio rerio) Embryo: Sensitivity and Specificity in Toxicity Assessment of Chemicals. AB - Studies using embryos of the zebrafish Danio rerio (DarT) instead of adult fish for characterising the (eco-) toxic potential of chemicals have been proposed as animal replacing methods. Effect analysis at the molecular level might enhance sensitivity, specificity, and predictive value of the embryonal studies. The present paper aimed to test the potential of toxicoproteomics with zebrafish eleutheroembryos for sensitive and specific toxicity assessment. 2-DE-based toxicoproteomics was performed applying low-dose (EC(10)) exposure for 48 h with three-model substances Rotenone, 4,6-dinitro-o-cresol (DNOC) and Diclofenac. By multivariate "pattern-only" PCA and univariate statistical analyses, alterations in the embryonal proteome were detectable in nonetheless visibly intact organisms and treatment with the three substances was distinguishable at the molecular level. Toxicoproteomics enabled the enhancement of sensitivity and specificity of the embryonal toxicity assay and bear the potency to identify protein markers serving as general stress markers and early diagnosis of toxic stress. PMID- 22084679 TI - Expression of Heat Shock and Other Stress Response Proteins in Ticks and Cultured Tick Cells in Response to Anaplasma spp. Infection and Heat Shock. AB - Ticks are ectoparasites of animals and humans that serve as vectors of Anaplasma and other pathogens that affect humans and animals worldwide. Ticks and the pathogens that they transmit have coevolved molecular interactions involving genetic traits of both the tick and the pathogen that mediate their development and survival. In this paper, the expression of heat shock proteins (HSPs) and other stress response proteins (SRPs) was characterized in ticks and cultured tick cells by proteomics and transcriptomics analyses in response to Anaplasma spp. infection and heat shock. The results of these studies demonstrated that the stress response was activated in ticks and cultured tick cells after Anaplasma spp. infection and heat shock. However, in the natural vector-pathogen relationship, HSPs and other SRPs were not strongly activated, which likely resulted from tick-pathogen coevolution. These results also demonstrated pathogen and tick-specific differences in the expression of HSPs and other SRPs in ticks and cultured tick cells infected with Anaplasma spp. and suggested the existence of post-transcriptional mechanisms induced by Anaplasma spp. to control tick response to infection. These results illustrated the complexity of the stress response in ticks and suggested a function for the HSPs and other SRPs during Anaplasma spp. infection. PMID- 22084680 TI - Comparative proteomic analysis of proteins involved in the tumorigenic process of seminal vesicle carcinoma in transgenic mice. AB - We studied the seminal vesicle secretion (SVS) of transgenic mice by using one dimensional gel electrophoresis combined with LTQ-FT ICR MS analysis to explore protein expression profiles. Using unique peptide numbers as a cut-off criterion, 79 proteins were identified with high confidence in the SVS proteome. Label-free quantitative analysis was performed by using the IDEAL_Q software program. Furthermore, western blot assays were performed to validate the expression of seminal vesicle proteins. Sulfhydryl oxidase 1, glia-derived nexin, SVS1, SVS3, and SVS6 showed overexpression in SVS during cancer development. With high sequence similarity to human semenogelin, SVS2 is the most abundance protein in SVS and is dramatically decreased during the tumorigenic process. Our results indicate that these protein candidates could serve as potential targets for monitoring seminal vesicle carcinoma. Moreover, this information can provide clues for investigating seminal vesicle secretion-containing seminal plasma for related human diseases. PMID- 22084681 TI - Cladribine and Fludarabine Nucleoside Change the Levels of CD Antigens on B Lymphoproliferative Disorders. AB - The purine analogs, fludarabine nucleoside (FdA), and cladribine (CdA) (1 MUM, 24 hours), significantly changed the levels of some surface antigens on the human B cell lines MEC2 and Raji. Changes in the surface proteins were identified using a Cluster of Differentiation (CD) antibody microarray that captures live cells and confirmed by flow cytometry. For Raji cells, CdA up-regulated CD10, CD54, CD80, and CD86, with repression of CD22, while FdA up-regulated CD20, CD54, CD80, CD86 and CD95. For MEC2 cells, CdA up-regulated CD11a, CD20, CD43, CD45, CD52, CD54, CD62L, CD80, CD86, and CD95, but FdA had no effect. Up-regulation of particular CD antigens induced on a B-cell lymphoproliferative disorder by a purine analog could provide targets for therapeutic antibodies with synergistic cell killing. PMID- 22084682 TI - Proteomics in melanoma biomarker discovery: great potential, many obstacles. AB - The present clinical staging of melanoma stratifies patients into heterogeneous groups, resulting in the application of aggressive therapies to large populations, diluting impact and increasing toxicity. To move to a new era of therapeutic decisions based on highly specific tumor profiling, the discovery and validation of new prognostic and predictive biomarkers in melanoma is critical. Genomic profiling, which is showing promise in other solid tumors, requires fresh tissue from a large number of primary tumors, and thus faces a unique challenge in melanoma. For this and other reasons, proteomics appears to be an ideal choice for the discovery of new melanoma biomarkers. Several approaches to proteomics have been utilized in the search for clinically relevant biomarkers, but to date the results have been relatively limited. This article will review the present work using both tissue and serum proteomics in the search for melanoma biomarkers, highlighting both the relative advantages and disadvantages of each approach. In addition, we review several of the major obstacles that need to be overcome in order to advance the field. PMID- 22084684 TI - Protein biomarkers for the early detection of breast cancer. AB - Advances in breast cancer control will be greatly aided by early detection so as to diagnose and treat breast cancer in its preinvasive state prior to metastasis. For breast cancer, the second leading cause of cancer-related death among women in the United States, early detection does allow for increased treatment options, including surgical resection, with a corresponding better patient response. Unfortunately, however, many patients' tumors are diagnosed following metastasis, thus making it more difficult to successfully treat the malignancy. There are, at present, no existing validated plasma/serum biomarkers for breast cancer. Only a few biomarkers (such as HER-2/neu, estrogen receptor, and progesterone receptor) have utility for diagnosis and prognosis. Thus, there is a great need for new biomarkers for breast cancer. This paper will focus on the identification of new serum protein biomarkers with utility for the early detection of breast cancer. PMID- 22084683 TI - Secretome Analysis of Skeletal Myogenesis Using SILAC and Shotgun Proteomics. AB - Myogenesis, the formation of skeletal muscle, is a multistep event that commences with myoblast proliferation, followed by cell-cycle arrest, and finally the formation of multinucleated myotubes via fusion of mononucleated myoblasts. Each step is orchestrated by well-documented intracellular factors, such as cytoplasmic signalling molecules and nuclear transcription factors. Regardless, the key step in getting a more comprehensive understanding of the regulation of myogenesis is to explore the extracellular factors that are capable of eliciting the downstream intracellular factors. This could further provide valuable insight into the acute cellular response to extrinsic cues in maintaining normal muscle development. In this paper, we survey the intracellular factors that respond to extracellular cues that are responsible for the cascades of events during myogenesis: myoblast proliferation, cell-cycle arrest of myoblasts, and differentiation of myoblasts into myotubes. This focus on extracellular perspective of muscle development illustrates our mass spectrometry-based proteomic approaches to identify differentially expressed secreted factors during skeletal myogenesis. PMID- 22084685 TI - Proteomics in pancreatic cancer research. AB - Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and deeply affects the life of people. Therefore, the earlier diagnosis and better treatments are urgently needed. In recent years, the proteomic technologies are well established and growing rapidly and have been widely applied in clinical applications, especially in pancreatic cancer research. In this paper, we attempt to discuss the development of current proteomic technologies and the application of proteomics to the field of pancreatic cancer research. This will explore the potential perspective in revealing pathogenesis, making the diagnosis earlier and treatment. PMID- 22084686 TI - Phosphorylation: the molecular switch of double-strand break repair. AB - Repair of double-stranded breaks (DSBs) is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ), homologous recombination (HR), or the inclusive DNA damage response (DDR). These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms. PMID- 22084687 TI - Clinical utility of serum autoantibodies detected by protein microarray in melanoma. AB - Better prognostic and predictive markers in melanoma are needed to select patients for therapy. We utilized a dual-lectin affinity chromatography and a natural protein microarray-based analysis to select a subproteome of target glycoproteins to profile serum antibodies against melanoma associated antigens that may predict nodal positivity. We identified 5 melanoma-associated antigens using this microarray coupled to mass spectrometry; GRP75, GRP94, ASAH1, CTSD and LDHB. We evaluated their predictive value for nodal status adjusting for age, gender, Breslow thickness, mitotic rate and ulceration using standard logistic regression. After adjustment, ASAH1, CTSD and LDHB were significantly negatively associated with nodal status (P = 0.0008) and GRP94 was significantly positively associated (P = 0.014). Our best multivariate model for nodal positivity included Breslow thickness, presence of serum anti-ASAH1, anti-LDHB or anti-CTSD, and presence of serum anti-GRP94, with an area under the ROC curve of 0.869. If validated, these results show promise for selecting clinically node negative patients for SLN biopsy. In addition, there is strong potential for glycoprotein microarray to screen serum autoantibodies that may identify patients at high risk of distant metastases or those likely or unlikely to respond to treatment, and these proteins may serve as targets for intervention. PMID- 22084688 TI - PolyAlign: A Versatile LC-MS Data Alignment Tool for Landmark-Selected and Automated Use. AB - We present a versatile user-friendly software tool, PolyAlign, for the alignment of multiple LC-MS signal maps with the option of manual landmark setting or automated alignment. One of the spectral images is selected as a reference map, and after manually setting the landmarks, the program warps the images using either polynomial or Hermite transformation. The software provides an option for automated landmark finding. The software includes a very fast zoom-in function synchronized between the images, which facilitate detecting correspondences between the adjacent images. Such an interactive visual process enables the analyst to decide when the alignment is satisfactory and to correct known irregularities. We demonstrate that the software provides significant improvements in the alignment of LC-MALDI data, with 10-15 landmark pairs, and it is also applicable to correcting electrospray LC-MS data. The results with practical data show substantial improvement in peak alignment compared to MZmine, which was among the best analysis packages in a recent assessment. The PolyAlign software is freely available and easily accessible as an integrated component of the popular MZmine software, and also as a simpler stand-alone Perl implementation to preview data and apply landmark directed polynomial transformation. PMID- 22084689 TI - Heat shock proteins in association with heat tolerance in grasses. AB - The grass family Poaceae includes annual species cultivated as major grain crops and perennial species cultivated as forage or turf grasses. Heat stress is a primary factor limiting growth and productivity of cool-season grass species and is becoming a more significant problem in the context of global warming. Plants have developed various mechanisms in heat-stress adaptation, including changes in protein metabolism such as the induction of heat shock proteins (HSPs). This paper summarizes the structure and function of major HSPs, recent research progress on the association of HSPs with grass tolerance to heat stress, and incorporation of HSPs in heat-tolerant grass breeding. PMID- 22084690 TI - Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia (A T) Patients Using a LC/MS-Based Label-Free Protein Quantification Technology. AB - Cerebrospinal fluid (CSF) has been used for biomarker discovery of neurodegenerative diseases in humans since biological changes in the brain can be seen in this biofluid. Inactivation of A-T-mutated protein (ATM), a multifunctional protein kinase, is responsible for A-T, yet biochemical studies have not succeeded in conclusively identifying the molecular mechanism(s) underlying the neurodegeneration seen in A-T patients or the proteins that can be used as biomarkers for neurologic assessment of A-T or as potential therapeutic targets. In this study, we applied a high-throughput LC/MS-based label-free protein quantification technology to quantitatively characterize the proteins in CSF samples in order to identify differentially expressed proteins that can serve as potential biomarker candidates for A-T. Among 204 identified CSF proteins with high peptide-identification confidence, thirteen showed significant protein expression changes. Bioinformatic analysis revealed that these 13 proteins are either involved in neurodegenerative disorders or cancer. Future molecular and functional characterization of these proteins would provide more insights into the potential therapeutic targets for the treatment of A-T and the biomarkers that can be used to monitor or predict A-T disease progression. Clinical validation studies are required before any of these proteins can be developed into clinically useful biomarkers. PMID- 22084691 TI - Glycoproteomics-based identification of cancer biomarkers. AB - Protein glycosylation is one of the most common posttranslational modifications in mammalian cells. It is involved in many biological pathways and molecular functions and is well suited for proteomics-based disease investigations. Aberrant protein glycosylation may be associated with disease processes. Specific glycoforms of glycoproteins may serve as potential biomarkers for the early detection of disease or as biomarkers for the evaluation of therapeutic efficacy for treatment of cancer, diabetes, and other diseases. Recent technological developments, including lectin affinity chromatography and mass spectrometry, have provided researchers the ability to obtain detailed information concerning protein glycosylation. These in-depth investigations, including profiling and quantifying glycoprotein expression, as well as comprehensive glycan structural analyses may provide important information leading to the development of disease related biomarkers. This paper describes methodologies for the detection of cancer-related glycoprotein and glycan structural alterations and briefly summarizes several current cancer-related findings. PMID- 22084692 TI - Venous thromboembolism: classification, risk factors, diagnosis, and management. AB - Venous thromboembolism (VTE) is categorised as deep venous thrombosis (DVT) and pulmonary embolism (PE). VTE is associated with high morbidity and causes a huge financial burden on patients, hospitals, and governments. Both acquired and hereditary risks factors contribute to VTE. To diagnose VTE, noninvasive cost effective diagnostic algorithms including clinical probability assessment and D dimer measurement may be employed followup by compression ultrasonography for suspected DVT patients and multidetector computed tomography angiography for suspected PE patients. There are pharmacological and mechanical interventions to manage and prevent VTE. The pharmacological approaches mainly target pathways in coagulation cascade nonspecifically: conventional anticoagulants or specifically: new generation of anticoagulants. Excess bleeding is one of the major risk factors for pharmacological interventions. Hence, nonpharmacological or mechanical approaches such as inferior vena cava filters, graduated compression stockings, and intermittent pneumatic compression devices in combination with pharmacological interventions or alone may be a good approach to manage VTE. PMID- 22084693 TI - Hepatitis C virus-related lymphomagenesis in a mouse model. AB - B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor alpha-subunit (sIL-2Ralpha) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1(_/_)/CN2 mice). Irf 1(_/_)/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes. PMID- 22084694 TI - POEMS Syndrome Presentation with an Abscess within the Plasmacytoma-A Rare Case Report. AB - POEMS Syndrome is a rare cause of demyelinating and axonal mixed neuropathy. Plasmacytomas are usually seen in POEMS syndrome and can be osseous or extramedullary. Plasmacytomas presenting as an abscess has not been noted earlier. Our patient presented with localized hyperpigmented patch on the back and later developed progressive weakness in upper and lower limbs. Initially serum and urine protein electrophoresis were normal. The patient was thought to have Chronic Inflammatory Demyelinating Polyneuropathy and was treated accordingly without any improvement. Repeat serum protein electrophoresis showed monoclonal gammopathy. MRI of the back revealed an abscess in the paravertebral soft tissues reaching up to the skin. Needle biopsy was consistent with plasmacytoma. Later, he developed a purulent fungating lesion in the lower midback. Antibiotics were started and local resection was done followed by radiation. Pathology of the resected mass showed plasmacytoma extensively involving subcutaneous soft tissue and bone. The patient improved with the treatment. Cystic plasmacytomas and abscess within the plasmacytoma has not been reported earlier. Whether abscess formation is part of the disease spectrum due to infiltration of overlying tissue or is secondary to localized immunosuppression is unknown. Local treatment of a single plasmacytoma is useful in ameliorating systemic symptoms. PMID- 22084695 TI - Relapse of Acute Myeloid Leukemia with t(16;21)(p11;q22) Mimicking Autoimmune Pancreatitis after Second Allogeneic Bone Marrow Transplantation. AB - We report the case of a 37-year-old woman who had a relapse of acute myeloid leukemia (AML) during treatment for chronic graft versus host disease (cGVHD) after allogeneic bone marrow transplantation. She was originally suspected of having autoimmune pancreatitis. Relapse of AML often occurs at extramedullary sites. Whereas the pancreas is rare as an organ of AML relapse, physicians should be aware that enlargement of the pancreas could be a sign of relapsed AML when excluding autoimmune pancreatitis, particularly during active cGVHD after allogeneic stem cell transplantation. PMID- 22084696 TI - Management of warfarin anticoagulation in patients with fractured neck of femur. AB - Background. Most orthopaedic units do not have a policy for reversal of anticoagulation in patients with hip fractures. The aim of this study was to examine the current practice in a district general hospital and determine difference in the time to surgery, if any, with cessation of warfarin versus cessation and treatment with vitamin K. Methods. A retrospective review of the case notes between January 2005 and December 2008 identified 1797 patients with fracture neck of femur. Fifty seven (3.2%) patients were on warfarin at the time of admission. Patients were divided into 2 groups (A and B). Group A patients (16/57; 28%) were treated with cessation of warfarin only and group B patients (41; 72%) received pharmacological therapy in addition to stopping warfarin. Time to surgery between the two groups was compared. Results. The mean INR on admission was 2.9 (range 1.7-6.5) and prior to surgery 1.4 (range 1.0-2.1). Thirty eight patients received vitamin K only and 3 patients received fresh frozen plasma and vitamin K. The average time to surgery was 4.4 days in group A and 2.4 days in group B. The difference was statistically significant (P < .01). Conclusion. Reversal of high INR is important to avoid significant delay in surgery. There is a need for a national policy for reversing warfarin anticoagulation in patients with hip fractures requiring surgery. Vitamin K is safe and effective for anticoagulation reversal in hip fracture patients. PMID- 22084697 TI - Coexistence of plasma cell dyscrasia with prefibrotic stage of primary myelofibrosis: a case report. AB - Introduction. Coexistence of myeloproliferative neoplasms with lymphoproliferative syndromes has been described in the past, whereas plasma cell dyscrasias seem to be the most common cases. Case Presentation. We present a case of a 59-year-old Caucasian female of Greek origin who presented with thrombocytosis. Clinical and laboratory investigation disclosed the presence of a smoldering myeloma with coexisting histological and molecular characteristics of primary myelofibrosis. The patient had the acquired point mutation V617F in the JAK2 gene but not the bcr-abl rearrangement and was treated for myelofibrosis with subsequent improvement of all haematological parameters without evidence of myelomatic evolution. Conclusion. We present the first case in the literature of a smoldering myeloma coexisting with primary myelofibrosis. The underlying pathogenetic mechanism could be either related to the presence of a pluripotent neoplastic stem cell capable to differentiate into both lymphoid and myeloid cells or be related to two separate nosologic entities. PMID- 22084698 TI - Iron depletion: an ameliorating factor for sickle cell disease? AB - We report some observations from our laboratory practice that might be important for the treatment of sickle cell disease (SCD). We describe data from two cases indicating that iron depletion might have a beneficial effect diminishing the formation of HbS in favor of HbF, possibly reducing the severity of the disease. We believe that it would be worthwhile to monitor the course of the disease comparing cases with identical genotypes with and without iron depletion, and we advise to consider chelation therapy to reduce iron overload in patients with SCD. PMID- 22084699 TI - Extranodal MALT Lymphoma of the Right Triceps Muscle following Influenza Vaccine Injection: A Rare Case with an Interesting Presentation. AB - The study describes a case of a 67-year-old female who developed a Stage I E marginal zone lymphoma of the right triceps muscle 1 month after influenza vaccination at the same site. She was treated with single modality, involved field radiation therapy (IFRT) to 4000 cGy in 20 fractions with excellent response and no evidence of disease after one year followup. PMID- 22084701 TI - The role of albumin in human toxicology of cobalt: contribution from a clinical case. AB - The distribution and adverse effects, especially to optic and acoustic nerves, of cobalt released from a hip arthroplasty and its association with albumin were studied. The analysis of cobalt was performed in plasma, whole blood, urine, and cerebrospinal fluid by inductively coupled plasma mass spectrometry (ICP-MS). The fraction of albumin binding the metal was determined by colorimetric assay using dithiothreitol (DTT). In all the biological matrices very high levels of cobalt were measured, but contrary to expected, a higher concentration in whole blood than in plasma was observed. The determination of altered albumin confirmed this hypothesis. This evidence might indicate an alteration in the binding of cobalt to albumin and a consequent increase in the concentration of the diffusible (free) fraction of the metal. This appears an interesting starting point for further investigations for identifying and better understanding cobalt neurotoxicity, apparently not so frequent in occupational medicine and clinical practice. PMID- 22084700 TI - A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma. AB - Anthracycline-based chemotherapy remains standard treatment for peripheral T-cell lymphoma (PTCL) although its benefits have been questioned. We performed systematic literature review and meta-analyses examining the complete response (CR) and overall survival (OS) rates for patients with PTCL. The CR rate for PTCL patients ranged from 35.9% (95% CI 23.4-50.7%) for enteropathy-type T-cell lymphoma (ETTL) to 65.8% (95% CI 54.0-75.9%) for anaplastic large cell lymphoma (ALCL). The 5-year OS was 38.5% (95% CI 35.5-41.6%) for all PTCL patients and ranged from 20.3% (95% CI 12.5-31.2%) for ETTL to 56.5% (95% CI 42.8-69.2%) for ALCL. These data suggest that there is marked heterogeneity across PTCL subtypes in the benefits of anthracycline-based chemotherapy. While anthracyclines produce CR in half of PTCL patients, this yields reasonable 5-year OS for patients with ALCL but not for those with PTCL-NOS or ETTL. Novel agents and regimens are needed to improve outcomes for these patients. PMID- 22084702 TI - Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia/Duarte alpha(2)beta(2)). AB - WE REPORT THE FIRST CASE OF COSEGREGATION OF TWO HAEMOGLOBINS (HBS): HbG Philadelphia [alpha68(E17)Asn -> Lys] and HbDuarte [beta62(E6)Ala -> Pro]. The proband is a young patient heterozygous also for beta degrees -thalassaemia. We detected exclusively two haemoglobin variants: HbDuarte and HbG Philadelphia/Duarte. Functional study of the new double variant HbG Philadelphia/Duarte exhibited an increase in oxygen affinity, with a slight decrease of cooperativity and Bohr effect. This functional behaviour is attributed to beta62Ala -> Pro instead of alpha68Asn -> Lys substitution. Indeed, HbG-Philadelphia isolated in our laboratory from blood cells donor carrier for this variant is not affected by any functional modification, whereas purified Hb Duarte showed functional properties very similar to the double variant. NMR and MD simulation studies confirmed that the presence of Pro instead of Ala at the beta62 position produces displacement of the E helix and modifications of the tertiary structure. The substitution alpha68(E17)Asn -> Lys does not cause significant structural and dynamical modifications of the protein. A possible structure-based rational of substitution effects is suggested. PMID- 22084703 TI - Hematological reference values for healthy adults in togo. AB - The hematological reference values are very important for diagnostic orientation and treatment decision. The aim of this study was to establish hematological reference values for healthy adults in Togo. A total of 2571 voluntary blood donors participated to this study. Only 1349 subjects negative for HIV, HBV, HCV, malaria, and without hemoglobin abnormalities in electrophoresis and hypochromia on blood smear, were definitively retained for the study. Median hemoglobin level was higher in males than females (15.1 g/dL versus 13.0 g/dL, p = 0.000). Median total WBC (4.2*10(9)/L) and absolute neutrophil counts (1.6*10(9)/L) were similar by gender. The median lymphocyte counts in males and females were, respectively, 2.1*10(9)/L and 2.2*10(9)/L (p = 0.11). The median platelet count was lower in males than females (236*10(9)/L versus 247*10(9)/L, p = 0.004). Our median values for RBC parameters differ from those of African countries probably because of our inclusion criteria which eliminate most cases with iron deficiency and/or thalassemia. PMID- 22084704 TI - Hemoglobin disorders in South India. AB - Cation exchange-high performance liquid chromatography (CE-HPLC) is increasingly being used as a first line of investigation for hemoglobinopathies and thalassemias. Together with a complete blood count, the CE-HPLC is effective in categorizing hemoglobinopathies as traits, homozygous disorders and compound heterozygous disorders. We carried out a one year study in Apollo Hospitals, Chennai (Tamil Nadu, South India) during which 543 abnormal chromatogram patterns were seen. The commonest disorder we encountered was beta-thalassemia trait (37.9%), followed by HbE trait (23.2%), homozygous HbE disease (18.9%), HbS trait (5.3%), HbE beta-thalassemia (4.6%), HbS beta-thalassemia (2.5%), beta thalassemia major (2.3%), HbH (1.6%), homozygous HbS (1.4%), HbD trait (0.7%). The average value of HbA2 in beta-thalassemia minor was 5.4%. beta-thalassemia major had an average HbF of 88% and in HbH the mean A2 was 1.4%. Among the HbE disorders the HbA2 + HbE was 30.1% in the heterozygous state, 90.8% in the homozygous state and 54.8% in HbE beta-thalassemia. In the sickle cell disorders, HbS varied from 30.9% in the trait to 79.9% in the homozygous state to 65.6% in HbS beta-thalassemia. PMID- 22084705 TI - Late effect of the cervical irradiation on periodontal status and cariogen flora in hodgkin lymphoma patients. AB - Cervical radiotherapy may leads to elevated caries risk in Hodgkin-lymphoma (HL) patients. Our aim was to estimate the late effect of cervical irradiation on periodontal status in HL patients. Patients filled out query-form, their clinical data were collected, periodontal status was examined, decayed-missing-filled teeth and periodontal-indexes were calculated. We examined 68 patients who received, 64 patients who did not received cervical radiotherapy and 51 control person. 23.5% of cervical irradiated, 18.15% of not irradiated patients and 17.64% of controls had subjective xerostomia, but it was not objective by sialometry. Mean decayed-missing-filled-teeth-index was 22.53 among irradiated, 21.54 among not irradiated patients while it was 17.23 in control group. Periodontal index was 2.47, 2.42, and 2.14 in different groups. Difference between decayed-missing-filled-teeth indexes of irradiated patients and controls was significant. We have to emphasize the importance of prevention and closer dental observation of HL patients. PMID- 22084706 TI - Splenic complications of sickle cell anemia and the role of splenectomy. AB - Sickle cell disease is one of the common hemoglobinopathies in the world. It can affect any part of the body and one of the most common and an early organ to be affected in SCA is the spleen. It is commonly enlarged during the first decade of life but then undergoes progressive atrophy leading to autosplenectomy. This however is not the case always and sometimes splenomegaly persist necessitating splenectomy for a variety of reasons including acute splenic sequestration crisis, hypersplenism, massive splenic infarction and splenic abscess. Splenic complications of SCA are known to be associated with an increased morbidity and in some it may lead to mortality. To obviate this, splenectomy becomes an essential part of their management. This review is based on our experience in the management of 173 children with various splenic complications of SCA necessitating splenectomy. PMID- 22084707 TI - Clinical challenges of primary diffuse large B-cell lymphoma of the dura: case report and literature review. AB - Primary dural lymphoma is a rare disease with more indolent clinical behavior compared to primary central nervous system lymphoma. The majority of the reported cases were indolent marginal zone lymphoma subtype with more predilections to the spine. Herein, we are presenting a case of intracranial, diffuse large B-cell lymphoma of the dura that was diagnosed and treated at our institution. We are presenting the challenges in the treatment based on a review of the literature. PMID- 22084708 TI - Antitumor Activity of Citrus maxima (Burm.) Merr. Leaves in Ehrlich's Ascites Carcinoma Cell-Treated Mice. AB - Context. The plant Citrus maxima Merr. (Rutaceae), commonly known as shaddock or pomelo is indigenous to tropical parts of Asia. The objective of present study is to evaluate the methanol extract of Citrus maxima leaves for its antitumor activity against Ehrlich's Ascites Carcinoma cell in Swiss albino mice. Experimental design. The antitumor activity of methanol extract of Citrus maxima leaves (MECM) was evaluated against Ehrlich Ascites Carcinoma (EAC) cell line in Swiss albino mice. 2 * 10(6) cells were inoculated in different groups of animals. MECM (200 and 400 mg/kg BW i.p.) was administered for nine consecutive days. On day 10th half the animals of different groups were sacrificed for determination of tumor and haematological parameters and the rest half were kept with sufficient food and water ad libitum for determination of increase in life span. Result and Discussions. Oral administration of the extract at the doses of 200 and 400 mg/kg significantly decreased tumor parameters such as tumor volume, viable tumor cell count and increased body weight, hematological parameters and life span in respect of the EAC control mice. Conclusion. Experimental design exhibits significant antitumor activity of the extract (MECM) in a dose dependant manner. PMID- 22084709 TI - Evaluation of genetic variations in organic cationic transporter 3 in depressed and nondepressed subjects. AB - Organic cationic transporter 3 (OCT3, SLS22A3) has only recently emerged as one of the regulators of monoaminergic neurotransmission, which plays a critical role in the pathogenesis of depression and is a potential new antidepressant drug target. OCT3 single-nucleotide polymorphisms (SNPs) have been investigated for their association with psychiatric disorders such as methamphetamine use disorder and obsessive-compulsive disorder in children and adolescents, but not depression. This study was designed to evaluate the allele frequencies of seven OCT3 SNPs in a US Caucasian depressed population and compare these frequencies with a control group of nondepressed subjects. Informed consent and a DNA sample were obtained from 157 subjects and analysis was performed using real-time PCR. Allele and genotype frequencies were compared using a t-test and the Pearson chi square analysis, respectively. There were no significant differences in OCT3 allele or genotype frequencies between the depressed and non-depressed groups for all seven SNPs evaluated. PMID- 22084710 TI - Novel Phenazine 5,10-Dioxides Release OH in Simulated Hypoxia and Induce Reduction of Tumour Volume In Vivo. AB - Phenazine 5,10-dioxides (PDOs) are a new class of bioreductive cytotoxins, which could act towards tumours containing hypoxic regions. The PDOs selective-hypoxic bioreduction was probed in vitro; however, the mechanism of action has not been completely explained. Besides, PDOs in vivo antitumour activities have not been demonstrated hitherto. We study the mechanism of hypoxic/normoxic cytotoxicity of PDO representative members. Electron spin resonance is used to confirm (*)OH production, alkaline comet assay to determine genotoxicity, and gel electrophoresis and flow cytometry to analyze DNA fragmentation and cell cycle distribution. Chemically induced rat breast tumours are employed to evaluate in vivo activities. For the most selective cytotoxin, 7(8)-bromo-2-hydroxyphenazine 5,10-dioxide (PDO1), exclusive hypoxic (*)OH production is evidenced, while for the unselective ones, (*)OH is produced in both conditions (normoxia and simulated hypoxia). In normoxia (Caco-2 cells), PDO1 induces cell-cycle arrest and DNA fragmentation but does not significantly induce apoptosis neither at IC(50) nor IC(80). No difference in the comet-assay scores are observed in normoxia and simulated hypoxia being the unselective 2-amino-7(8)-bromophenazine 5,10-dioxide (PDO2) the most genotoxic. The in vivo efficacy with the absence of systemic toxicity of PDO1 and PDO2 is checked out. Results from this study highlight the potential of PDOs as new therapeutics for cancer. PMID- 22084711 TI - Dendritic cell-based graft tolerance. AB - It has recently been demonstrated that mouse and human dendritic cells (DCs) can produce IL-2 after activation. However the role of the IL2/IL2R pathway in DC functions has not yet been fully elucidated. The results presented in this study provide several new insights into the role of this pathway in DCs. We report that stimulation of human monocyte-derived DCs with LPS strongly upregulated CD25 (alpha chain of the IL2R) expression. In additon, by using a humanized monoclonal antibody against CD25, we demonstrated that the IL2 signalling in DC upregulated both IL-12 and gammaIFN production but decreased IL10 synthesis. We also found that LPS-matured DCs produced IL2. Taken together, these results suggest that IL 2 actively contributes to the DC activation through an autocrine pathway. Furthermore, our results indicate that the IL2 pathway in DC is involved in the development of T-helper priming ability and in the upregulation of surface markers characteristic of a "mature" phenotype. This study therefore provide new molecular clues regarding the split between these two phenomena and unravel new mechanisms of action of anti-CD25 monoclonal antibodies that may contribute to their action in several human immunological disorders such as autoimmune diseases and acute allograft rejection. PMID- 22084712 TI - Bioremediation of pharmaceuticals, pesticides, and petrochemicals with gomeya/cow dung. AB - Use and misuse of pharmaceuticals, pesticides, and petrochemicals by man is causing havoc with nature, as they persist as such or as their toxic metabolites. These pollutants bioaccumulate in environment, and they ultimately reach man through various means. They are hazardous because of potential toxicity, mutagenicity, carcinogenicity, and genotoxicity. To rejuvenate nature, remediation methods currently available are usually expensive and might convert one toxic pollutant to another. Bioremediation methods use naturally occurring microorganisms to detoxify man-made pollutants so that they change pollutants to innocuous products that make soil fertile in the process. Taking cue from Ayurveda, Gomeya/cow dung is used as an excellent bioremediation method. Thus, utilizing freely available cow dung as slurry or after composting in rural areas, is a cheap and effective measure to bioremediate the harmful pollutants. Yet, more research in this direction is warranted to bioremediate nonbiodegradable, potentially toxic pollutants. PMID- 22084713 TI - Carvedilol-Afforded Protection against Daunorubicin-Induced Cardiomyopathic Rats In Vivo: Effects on Cardiac Fibrosis and Hypertrophy. AB - Anthracyclines, most powerful anticancer agents, suffer from their cardiotoxic effects, which may be due to the induction of oxidative stress. Carvedilol, a third-generation, nonselective beta-adrenoreceptor antagonist, possesses both reactive oxygen species (ROS) scavenging and ROS suppressive effects. It showed protective effects against daunorubicin- (DNR-) induced cardiac toxicity by reducing oxidative stress and apoptosis. This study therefore was designed to examine the effects of carvedilol on DNR-induced cardiomyopathic rats, focused on the changes of left ventricular function, cardiac fibrosis, and hypertrophy. Carvedilol increased survival rate, prevented systolic and diastolic dysfunction, and attenuated myocardial fibrosis and hypertrophy. DNR alone treated rats showed upregulated myocardial expression of ANP, PKC-alpha, OPN, and TGF-beta1 and downregulation of GATA-4 in comparison with control, and treatment with carvedilol significantly reversed these changes. The results of the present study add the available evidences on the cardioprotection by carvedilol when associated with anthracyclines and explain the mechanisms underlying the benefits of their coadministration. PMID- 22084714 TI - Effect of rosmarinic and caffeic acids on inflammatory and nociception process in rats. AB - Rosmarinic acid is commonly found in species of the Boraginaceae and the subfamily Nepetoideae (Lamiaceae). It has a number of interesting biological activities, for example, antiviral, antibacterial, anti-inflammatory, and antioxidant. The aim of the present study was to investigate the effect of the i.p. administration of caffeic and rosmarinic acid (5 and 10 mg/kg) on anti inflammatory and nociceptive response using carrageenan-induced pleurisy model and tail-flick assay in rats. The analysis of cells in the pleural exudates revealed a reduction of 66% of the number of leukocytes that migrated to the pleural cavity in the animals treated with 5 mg/kg caffeic acid, and of 92.9% for the animals treated with 10 mg/kg in comparison with the control group. These exudates showed a balanced distribution of polymorphonuclear (PMN) and mononuclear (MN) cells, differently from the control group, in which PMN cells were predominant. The analysis to tail-flick latency was increased in the group treated with 10 mg/kg caffeic acid characterizing a nociceptive response. While there was no difference between control group and animals treated with rosmarinic. PMID- 22084715 TI - Efficacy and Safety of COX-2 Inhibitors in the Clinical Management of Arthritis: Mini Review. AB - In the clinical management of arthritis, the choice of nonsteroidal anti inflammatory drug (NSAID) remains confusing and controversial. A common practice on the choice of NSAID in clinical management of arthritis is the risk benefit ratio. The main objective of this review is to addresses the main arguments for the pharmacological and clinical use of COX-2 inhibitors in relation to nonselective NSAIDs for the clinical management of arthritis. This review concluded that, both NSAIDs and COX-2 inhibitors are equally effective and are associated with increased risk of GI, renal, and CV, adverse effects. Complete understanding of the patient's comorbid conditions and concomitant medications, coupled with precise monitoring during the treatment, may help to decrease the threat of adverse effects induced by nonselective NSAIDs and selective COX-2 inhibitors. PMID- 22084716 TI - Hypolipidemic and Antiobesity-Like Activity of Standardised Extract of Hypericum perforatum L. in Rats. AB - Hypericum perforatum is known to have diverse medicinal uses for centuries. The antidepressant activity of Hypericum perforatum is widely accepted and proved in both animal and clinical studies. Present study was undertaken to investigate the effect of Hypericum perforatum in a battery of animal models for metabolic disorder. Hypericum is tested for hypolipidemic activity in normal rats, antiobesity activity in high-fat-diet induced obese rats, and fructose-fed rats. Hypericum was orally administered as suspension in 0.3% carboxymethyl cellulose at the doses of 100 and 200 mg/kg body weight for 15 consecutive days. Hypericum significantly lowered total cholesterol and low-density cholesterol in normal rats. Hypericum significantly inhibited weight gain in high-fat-fed rats. In fructose-fed rats, Hypericum normalised the dyslipidemia induced by fructose feeding and improved the insulin sensitivity. Taken together, Hypericum could be the antidepressant therapy of choice for patients suffering from comorbid diabetes and obesity. PMID- 22084717 TI - Chloroformic and Methanolic Extracts of Olea europaea L. Leaves Present Anti Inflammatory and Analgesic Activities. AB - Olea europaea L. is used in traditional medicine in the Mediterranean areas. Its natural products are used in the treatment of different disorders, like fighting fever and some infectious diseases such as malaria, the treatment of arrhythmia, and relief of intestinal spasms. The aim of the current study is to investigate the possible anti-inflammatory and anatinociceptive effects of methanol and chloroformic extracts prepared from leaves of Olea europaea L. The anti inflammatory and antinociceptive effects of the different extracts of Olea europaea leaves were assessed after intraperitoneal administration into rats and mice, using the carrageenan-induced paw edema model in rats to test the anti inflammatory effect and the acetic acid-induced writhing in mice to test the analgesic effect. The chloroformic and methanolic leaves extracts, studied at the doses of 50, 100, and 200 mg/kg (Body Weight: BW), exhibited significant dose dependent anti-inflammatory and analgesic activities. Based on the results obtained, it can be concluded that Olea europaea leaves extracts have anti inflammatory and antinociceptive effects. PMID- 22084718 TI - Antioxidant Activity of Aspergillus fumigatus. AB - The antioxidant activity of Aspergillus fumigatus was assayed by different procedures and correlated with its extracellular total phenolic contents. Different physio-chemical parameters were optimized to enhance the activity. The culture grown under stationary conditions for 10 days at 25 degrees C at pH 7 gave the best antioxidant activity. Statistical approaches demonstrated sucrose and NaNO(3) to be the most suitable carbon and nitrogen sources, respectively. Response surface analysis showed 5% sucrose, 0.05% NaNO(3), and incubation temperature of 35 degrees C to be the optimal conditions for best expression of antioxidant activity. Under these conditions, the antioxidant potential assayed through different procedures was 89.8%, 70.1%, and 70.2% scavenging effect for DPPH radical, ferrous ion and nitric oxide ion, respectively. The reducing power showed an absorbance of 1.0 and FRAP assay revealed the activity of 60.5%. Extracellular total phenolic content and antioxidant activity as assayed by different procedures positively correlated. PMID- 22084719 TI - Control of Clinical Pathogens by the Haemolymph of Paratelphusa hydrodromous, a Freshwater Crab. AB - In the present study, effort has been made to find the antimicrobial activity of haemolymph collected from freshwater crab, Paratelphusa hydrodromous. The haemolymph collected was tested for antimicrobial assay by disc diffusion method against clinical pathogens. Five bacterial species, namely, Escherichia coli, Klebsiella pneumonia, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and five fungal strains, namely and Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Rhizopus sp., and Mucor sp., were selected for the study. The result shows a strong response of haemolymph against the clinical pathogens which confirms the immune mechanism of the freshwater crab. PMID- 22084720 TI - Studies on Wound Healing Activity of Heliotropium indicum Linn. Leaves on Rats. AB - The petroleum ether, chloroform, methanol, and aqueous extracts of Heliotropium indicum Linn. (Family: Boraginaceae) were separately evaluated for their wound healing activity in rats using excision (normal and infected), incision, and dead space wound models. The effects of test samples on the rate of wound healing were assessed by the rate of wound closure, period of epithelialisation, wound breaking strength, weights of the granulation tissue, determination of hydroxyproline, super oxide dismutase (SOD), catalase, and histopathology of the granulation tissues. Nitrofurazone (0.2% w/w) in simple ointment I. P. was used as reference standard for the activity comparison. The results revealed significant promotion of wound healing with both methanol and aqueous extracts with more promising activity with the methanol extract compared to other extracts under study. In the wound infection model (with S. aureus and P. aeruginosa), the methanol extract showed significant healing activity similar to the reference standard nitrofurazone. Significant increase in the granulation tissue weight, increased hydroxyproline content, and increased activity of SOD and catalase level with the animals treated with methanol extract in dead space wound model further augmented the wound healing potential of H. indicum. The present work substantiates its validity of the folklore use. PMID- 22084721 TI - Increased excretion of c4-carnitine species after a therapeutic acetylsalicylic Acid dose: evidence for an inhibitory effect on short-chain Fatty Acid metabolism. AB - Acetylsalicylic acid and/or its metabolites are implicated to have various effects on metabolism and, especially, on mitochondrial function. These effects include both inhibitory and stimulatory effects. We investigated the effect of both combined and separate oral acetylsalicylic acid and acetaminophen administration at therapeutic doses on the urinary metabolite profile of human subjects. In this paper, we provided in vivo evidence, in human subjects, of a statistically significant increase in isobutyrylcarnitine after the administration of a therapeutic dose of acetylsalicylic acid. We, therefore, propose an inhibitory effect of acetylsalicylic acid on the short-chain fatty acid metabolism, possibly at the level of isobutyryl-CoA dehydrogenase. PMID- 22084722 TI - Potential Agents against Plasma Leakage. AB - Shock due to severe plasma leakage may happen in infectious diseases such as severe dengue and sepsis due to various bacterial infections, which may be deleterious and may lead to death. Various substances and proteins are known to modulate the effects of proleakage mediators and counteract the deleterious effect of plasma leakage. Some of the various substances and proteins such as focal adhesion kinase (FAK), the Rho GTPases, protein kinase A, and caveolin-1 have dual actions; therefore they are not suitable for therapy. However, sphingosine 1phosphate and its receptor agonists, Angiopoetin-1, Slit, and Bbeta15-42 may be promising. PMID- 22084723 TI - Colon carcinoma presenting with a synchronous oesophageal carcinoma and Basal cell carcinoma of the skin. AB - With advances in diagnostic techniques and treatment modalities, the number of patients identified with colorectal carcinoma who develop multiple primary malignancies during long-term followup has been increasing. We report a patient who developed three histologically distinct malignancies. Primary colon carcinoma treated radically followed by an 8-year disease-free period. The patient then presented with progressive dysphagia and was investigated and diagnosed to have a synchronous multicentric squamous cell carcinoma of the oesophagus and basal cell carcinoma of the skin. There was a simultaneous multicentric recurrence in the colon. This case is worth mentioning because the clustering of three primary malignancies (synchronous and metachronous) is of rare occurrence in a single patient, and, to our knowledge, this is the first report of this combination occurring in the same individual. In addition, the report emphasizes the importance of evaluating patients with known colonic primary neoplasms for synchronous colonic and extracolonic tumors. PMID- 22084724 TI - Identification of HN-1-Peptide Target in Head and Neck Squamous Cell Carcinoma Cells. AB - The HN-1 module was previously reported to ensure efficient targeting of head and neck squamous cell carcinoma (HNSCC). Aim of this work was to indentify the target of HN-1. Targeting of HN-1 peptide was compared in normal epithelial cells (BEAS-2B) and in HNSCC tumor cells (SCC-25 and Detroit 562). Experimental, cell culture, cell polarity, and adhesion conditions were tested; structure models of peptides were created. Indeed, HN-1 was able to target HNSCC tumor cells in the previously published conditions. The targeting efficiency of immortalized normal epithelial cells was significantly lower. Nevertheless, in other experimental conditions the binding was less efficient and not specific. A scrambled sequence of HN-1, with altered order of amino acids showed even better targeting efficiency than HN-1. HN-1 was only uptaken in adherent cells, not in suspension. In conclusion, HN-1-peptide-targeting is not based on sequence specificity, but more on electrostatic interactions with the cell surface of the tumor cells. PMID- 22084725 TI - High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients. AB - Background. Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system-related genes are activated and have prognostic significance in Ewing's sarcoma family of tumors (ESFTs). Method. Data analysis was performed on gene expression profiles of 44 ESFT patients, 11 ESFT cell lines, and 18 normal skeletal muscle samples. Differential expression of 238 inflammation and 299 macrophage-related genes was analysed by t-test, and survival analysis was performed according to gene expression. Results. Inflammatory genes are activated in ESFT patient samples, as 38 of 238 (16%) inflammatory genes were upregulated (P < 0.001) when compared to cell lines. This inflammatory gene activation was characterized by significant enrichment of macrophage-related gene expression with 58 of 299 (19%) of genes upregulated (P < 0.001). High expression of complement component 5 (C5) correlated with better event-free (P = 0.01) and overall survival (P = 0.004) in a dose-dependent manner. C5 and its receptor C5aR1 expression was verified at protein level by immunohistochemistry on an independent ESFT tumour tissue microarray. Conclusion. Immune system-related gene activation is observed in ESFT patient samples, and prognostically significant inflammatory genes (C5, JAK1, and IL8) for ESFT were identified. PMID- 22084726 TI - Role and efficacy of intraoperative evaluation of resection adequacy in conservative breast surgery. AB - In the present study we considered the histology of 51 patients who have undergone breast conservative surgery and the related 54 re-excisions that were performed in the same surgical procedure or in delayed procedures, in order to evaluate the role of intraoperative re-excisions in completing tumor removal. In 13% of the cases the re excision obtained the resection of the target lesion. In this study, the occurrence of residual neoplastic lesions in intraoperative re excisions (24%) is lower than in delayed re-excisions (62%; P = .03). The residual lesions that we could find with definitive histology of re excision specimens are related with lesions with ill defined profile. In 77% of the cases of re excision with tumoral residual the lesion was close to the new resection margin, thus the re-excisions couldn't achieve an adequate ablation of the neoplasm. Invasive or preinvasive nature of the main lesion resected for each case and the approach to the evaluation of the first resection specimen adequacy (surgical or radiological) don't affect the rate of tumoral residual in intraoperative re-excisions. In conclusion, our data are consistent with a low efficacy of intraoperative re excision in obtaining a complete removal of the tumor; intraoperative radiologic evaluation of the first resection specimen is however imperative in defining the effective removal of the target lesion. PMID- 22084727 TI - The role of tobacco-derived carcinogens in pancreas cancer. AB - The extremely poor outcome from pancreas cancer is well known. However, its aetiology less well appreciated, and the molecular mechanisms underlying this are poorly understood. Tobacco usage is one of the strongest risk factors for this disease, and this is a completely avoidable hazard. In addition, there are well described hereditary diseases which predispose, and familial pancreas cancer. We have sought here to summarise the role of tobacco-derived carcinogens and the mode of their tumorigenic action on the pancreas. There is compelling evidence from animal and human studies (laboratory including cell line studies and epidemiologic) that tobacco derived carcinogens cause pancreas cancer. However, the manner in which they do so is not entirely apparent. There is also compelling evidence that synergism with genetic and other life-style factors-like diet obesity-results in a multifactorial causation of the disease. Ascertaining the role of tobacco carcinogens in the development of this cancer and their interaction with other risk factors will enable novel therapeutic and preventative strategies to improve outcome from this appalling malignancy. PMID- 22084728 TI - Anti-inflammatory drugs reduce the risk of hepatocellular carcinoma development. AB - Nowadays, patients with chronic hepatitis C in all countries are generally treated with interferon (IFN), and more than 50% of patients become HCV-RNA negative following PEG-IFN plus ribavirin therapy, but unfortunately, the IFN therapy is not effective in about 70% of patients with HCV-associated LC. In Japan, HCC actually develops in about 7% of those patients every year. A strategy for preventing HCC development other than IFN therapy is, therefore, urgently needed for those patients. We reported that the recurrence rate and the development of HCC was more rapid in the high serum ALT level (>80 IU) patients with HCV-associated LC. Sho-saiko-to, Juzen-taiho-to, and stronger-neo minophagen C are herbal medicines used in Japan to treat chronic viral liver diseases, and they work by reducing inflammatory processes and controlling ALT levels. Aggressive reduction therapy for ALT levels in HCV-LC patients could significantly prevent HCC development. PMID- 22084730 TI - Cytotoxic Activity of Peripheral Blood Mononuclear Leukocytes, Activated by Interleukin-2/beta-Cyclodextrin Nanocomposition against Androgen Receptor Negative Prostate Cancers. AB - Nanocomposition comprised of interleukin-2 in suboptimal noneffective concentration and beta-cyclodextrin was studied in vitro. This preparation as well as interleukin-2 in optimal concentration was shown to increase natural killer activity to K-562 cells and cytotoxicity of activated peripheral blood mononuclear cells (PBMCs) against PC-3 and DU 145 cells. At the same time beta cyclodextrin or interleukin-2 in equimolar concentrations did not influence the spontaneous killer activity of PBMC. This combination of cyclodextrin + interleukin-2 led to the decrease of interleukin-2 effective concentration by an order. This phenomenon could be explained by cyclodextrins ability to promote the formation of nanoparticles with drugs, which results in enhancing their water solubility and bioavailability. Besides, interleukine-2/beta-cyclodextrin nanocomposition as opposed to interleukin-2 alone led to increasing the number of not only lymphocytes, but also macrophages contained in activated PBMC population. Application of low concentration of interleukin-2 allowing for good clinical efficiency may significantly mitigate the side effects of the drug and enable to develop adoption of immunotherapy for patients with androgen-resistant prostate cancer. PMID- 22084729 TI - The chemopreventive properties and therapeutic modulation of green tea polyphenols in oral squamous cell carcinoma. AB - Chemoprevention is a relatively novel and promising approach for controlling cancer that uses specific natural products or synthetic agents to suppress, reverse, or prevent premalignancy before transformation into invasive cancer. Oral cavity squamous cell carcinoma (OCSCC) represents a large, worldwide health burden with approximately 274,000 cases diagnosed annually worldwide. Smoking and alcohol consumption are major inducers of OCSCC. Recently, the human papilloma virus was also shown to potentially be an etiologic factor. Due to its easily identifiable risk factors and the presence of premalignant regions, oral cancer makes a good candidate for chemoprevention. Green tea is the most widely consumed beverage in the world, and it has received considerable attention because of its abundant, scientifically proven, beneficial effects on human health. In this review, we discuss the role of green tea in oral cancer chemoprevention with regard to the multiple molecular mechanisms proposed in various in vitro, in vivo, and clinical trials. PMID- 22084731 TI - Cancer Risk and Behavioral Factors, Comorbidities, and Functional Status in the US Elderly Population. AB - About 80% of all cancers are diagnosed in the elderly and up to 75% of cancers are associated with behavioral factors. An approach to estimate the contribution of various measurable factors, including behavior/lifestyle, to cancer risk in the US elderly population is presented. The nationally representative National Long-Term Care Survey (NLTCS) data were used for measuring functional status and behavioral factors in the US elderly population (65+), and Medicare Claims files linked to each person from the NLTCS were used for estimating cancer incidence. The associations (i.e., relative risks) of selected factors with risks of breast, prostate, lung and colon cancers were evaluated and discussed. Behavioral risk factors significantly affected cancer risks in the US elderly. The most influential of potentially preventable risk factors can be detected with this approach using NLTCS-Medicare linked dataset and for further deeper analyses employing other datasets with detailed risk factors description. PMID- 22084732 TI - Olfactory neuroblastomas: an experience of 24 years. AB - Objective. The aim of this study was to evaluate clinicopathological findings and the efficacy of the treatment modalities used in patients with olfactory neuroblastomas. Study Design. Retrospective record review. Setting. Istanbul University, Cerrahpasa Medical Faculty, medical oncology outpatient clinic. Subjects and Methods. There were 3 stage A tumors, 5 stage B and 11 stage C according to the Kadish staging system. There were 5 grade I/II and 12 grade III/IV according to the Hyams' histopathologic system. Involvement to orbita was detected in eight patients at the time of diagnosis. Results. The median follow up period was 23.7 months. The 5-year survival rate for the whole group was 26%. The stage A/B groups exhibited a better survival rate than the C group with 2 year survival rates being 25 versus 71% respectively (P = .008). The grade I/II groups exhibited a better survival rate than the grade III/IV groups with 2-year survival rates being 50 versus 16% respectively (P = .001). The group who had orbital involvement exhibited a poor survival rate than the group of patients who had no involvement of the orbital. Conclusion. In our study, tumor stage, histopathologic grading, involvement of the orbita, brain and bone marow metastases were the statistically significant prognostic factors. PMID- 22084733 TI - Axillary dissection in breast cancer patients with metastatic sentinel node: to do or not to do? Suggestions from our series. AB - Several studies have put to question and evaluated the indication and prognosis of sentinel lymph node biopsy (SNLB) as sole treatment in human breast cancer. We reviewed 1588 patients who underwent axillary surgery. In 239 patients, axillary lymph node dissection (ALND) was performed following positive fine needle aspiration cytology (FNAC), and, in 299 cases, ALND was executed after positive SNLB. The most dramatic result from our data is that patients with either micrometastasis of the sentinel lymph node (SLN) or only metastatic SLN have, respectively, an 84.5% and a 75.0% chance of having no other nodal involvement. We believe a more refined patient selection is neccessary when considering ALND. Where the primary tumor is larger than 5 cm, where radio or adjuvant therapies are not indicated, in cases of FNAC+ nodes, and in cases presenting more than one metastatic sentinel node, we prefer to carry out ALND. Having thus said, however, our data suggests that it is wise not to perform ALND in almost all cases presenting positive SLNs. PMID- 22084734 TI - Differentiated thyroid cancer in navarra (Spain): historic cohort results (1987 2003). AB - Introduction. Navarra has the highest incidence of differentiated thyroid cancer in Spain. The aim of this study was to review its management carried out by the Navarra's multidisciplinary Thyroid Disease Unit, from 1987 to 2003. Material and Methods. 325 patients were studied to find the incidence, prevalence, and prognostic factors. Statistical analysis comprised univariate and multivariate Cox proportional hazards regression models for survival and tumor recurrence. Results. The average annual incidence was 3.6 per 100,000 inhabitants, with a final prevalence of 82.4 per 100,000. Regarding survival and recurrence, statistical significance was observed for stage IV, follicular carcinoma, capsular and prethyroid muscles invasion, and T4 group. Only survival was related to tumour size larger than 40 mm. Only recurrence was related to lymph node metastases and radioiodine dose higher than 100 mCi. Conclusions. Attendance of patients in a functional unit setting has allowed us to classify them into three risk groups. PMID- 22084735 TI - 3-5 BI-RADs Microcalcifications: Correlation between MRI and Histological Findings. AB - Purpose. To evaluate the correlation between MRI and histopathological findings in patients with mammographically detected 3-5 BI-RAD (Breast Imaging Reporting And Data Systems) microcalcifications and to allow a better surgical planning. Materials and Method. 62 female Patients (age 50 +/- 12) with screening detected 3-5 BI-RAD microcalcifications underwent dynamic 3 T contrast-enhanced breast MRI. After 30-day (range 24-36 days) period, 55 Patients underwent biopsy using stereotactic vacuum-assisted biopsy (VAB), 5 Patients underwent stereotactic mammographically guided biopsy, and 2 Patients underwent MRI-guided VAB. Results. Microhistology examination demonstrated 36 malignant lesions and 26 benign lesions. The analysis of MRI findings identified 8 cases of MRI BI-RADS 5, 23 cases of MRI BI-RADS 4, 11 cases of MRI BI-RADS 3, 4 cases type A and 7 cases type B, and 20 cases of MRI BI-RADS 1-2. MRI sensitivity, specificity, positive predictive value, and negative predictive value were 88.8%, 76.9%, 84.2%, and 83.3%, respectively. PMID- 22084736 TI - "Il corpo ritrovato": dermocosmetological skin care project for the oncologic patient. AB - Neoplastic disease and its therapeutic options have a huge impact on the patient's quality of life from both the emotional and the working point of view. The project "Il Corpo Ritrovato" aims at creating an interdisciplinary network of physicians to improve the quality of life of the oncologic patient, focusing on such important aspects as dermocosmetological skin care but also on the evaluation of new therapeutic and diagnostic algorithms in order to make further progress in the field of prevention. PMID- 22084737 TI - Does radioiodine therapy in patients with differentiated thyroid cancer increase the frequency of another malignant neoplasm? AB - Objectives. To compare the frequency of another primary malignancy in patients with differentiated thyroid carcinoma (DTC) who received radioiodine therapy or not ((131)I). Material and Methods. 168 cases of DTC patients were retrospectively evaluated as to the frequency of another neoplasia by comparing patients with and without it, taking into account clinical, laboratory, and therapeutic parameters. Results. Another primary malignancy occurred in 8.9% of patients. Of these, 53.3% showed the malignancy before (131)I and 46.7% after it. By comparing both groups, the age at the moment of diagnosis of another neoplasia was 46.1 +/- 20.2 years for the group before (131)I therapy and of 69.4 +/- 11.4 years for the group after it (P = 0.02). Of the 148 patients treated with (131)I, 4.7% developed another malignancy. The latter were older (61 +/- 17 years) than those who did not show another cancer type (44.1 +/- 14.2 years) (P < 0.05). Conclusion. The frequency of another neoplasia found after (131)I was similar to that found before (131)I. PMID- 22084738 TI - Cancers of the appendix: review of the literatures. AB - Cancers of the appendix are rare. Most of them are found accidentally on appendectomies performed for appendicitis. When reviewed, majority of the tumors were carcinoid, adenoma, and lymphoma. Adenocarcinomas of appendix are only 0.08% of all cancers and the treatment remains controversial. Here we are reporting a 46-year-old male presented with symptoms of appendicitis, diagnosed with adenocarcinoma of the appendix. The patient was treated with appendectomy and refused further surgical intervention to complete hemicolectomy. Up to date, he remains asymptomatic. We performed literature review of the tumors of the appendix. Most of the benign conditions are treated with surgery alone. Lymphomas require CHOP-like chemotherapy and carcinoid syndrome treatment with somatostatin analogues. It is generally recommended that right hemicolectomy is the preferred treatment for adenocarcinoma of appendix. The role of chemotherapy is unclear due to lacking randomized trials but seems to be accepted if there is lymph node involvement or peritoneal seeding. PMID- 22084739 TI - Angiomyolipoma of the right adrenal gland. AB - Adrenal angiomyolipoma is rare. Only four cases have been reported so far. These are commonly found in Kidney but extrarenal sites are also mentioned. Angiomyolipoma arising in adrenal is very rare entity, usually asymptomatic, diagnosed incidentally on radiological investigation of abdomen for other conditions. We report our experience with a 45-year-old woman who presented with epigastric discomfort. A computerised tomography (CT) scan showed an adrenal mass. Laparoscopic adrenalectomy was performed and the histopathological features confirmed the diagnosis of adrenal angiomyolipoma. The patient recovered without any complications following surgery. PMID- 22084740 TI - Living Donor Liver Transplantation for Caroli's Disease: A Report of Two Cases. AB - Caroli's disease (CD) is a rare autosomal recessive disorder characterized by intrahepatic cystic dilatation of the bile ducts. Patients with bilobar or progressive disease may require orthotopic liver transplantation (OLT). In the MELD era, living donor liver transplantation (LDLT) raised as the ultimate treatment option for these patients, once their MELD score is usually low. Herein, we describe 2 cases of patients (a 2-year-old girl and a 19-year-old teenager) that successfully underwent LDLT as a treatment for diffuse CD. The good postoperative courses of the two cases indicate that LDLT is a feasible option in the treatment of this disorder, even in complicated or early age patients. PMID- 22084741 TI - Congenital anterior urethral diverticulum in children: a case report and review. AB - Congenital anterior urethral diverticulum (CAUD) is an uncommon condition in children. We describe 2 patients of CAUD who presented with ventral penile swelling; in one, the site of swelling was just proximal to corona which is quite rare. The diagnosis was made on USG and MCU. Both patients had normal renal function. Open diverticulectomy and primary repair was done in both patients. PMID- 22084742 TI - Median nerve repair with autologous sciatic nerve graft: a case report. AB - Background. Peripheral nerve injury treatment options are limited to primary nerve repair, nerve grafting, and tendon transfers. In this case, a large suitable donor site was easily accessible and delayed grafting was indicative of poor prognosis. Case Description. A 25-year-old soldier presented to a military hospital in Afghanistan following a roadside bomb attack. The patient had a medial shrapnel wound in the bicipital groove with a cool pulseless hand and catastrophic lower extremity injuries. Bilateral above-the-knee amputations (AKAs) and exploration of the medial shrapnel wound were undertaken. A 7 cm traumatic defect in the median nerve was repaired with interpositional sciatic nerve graft harvested from the AKA. Conclusion. Recovery of motor function after nerve grafting is dependent on motor axons reinnervating target muscles, making proximal nerve injuries problematic. We identify a potential nerve harvest site in patients with lower extremity amputations in need of long segment nerve repairs. PMID- 22084743 TI - Subarachnoid-pleural fistula: applied anatomy of the thoracic spinal nerve root. AB - Subarachnoid-pleural fistula (SPF) is a rare complication of chest or spine operations for neoplastic disease. Concomitant dural and parietal pleural defects permit flow of cerebrospinal fluid into the pleural cavity or intrapleural air into the subarachnoid space. Dural injury recognized intraoperatively permits immediate repair, but unnoticed damage may cause postoperative pleural effusion, intracranial hypotension, meningitis, or pneumocephalus. We review two cases of SPF following surgical intervention for chest wall metastatic disease to motivate a detailed review of the anatomy of neural, osseous, and ligamentous structures at the intervertebral foramen. We further provide recommendations for avoidance and detection of such complication. PMID- 22084745 TI - Footballer's Lateral Meniscus: Anterior Horn Tears of the Lateral Meniscus with a Stable Knee. AB - This paper aimed to identify the characteristics of isolated anterior horn tear of the lateral meniscus in footballers who underwent arthroscopic surgery. We identified 8 patients with stable knee and no ligament injury, who had only isolated anterior horn tear of the lateral meniscus between 2007 and 2009. All 8 patients were footballers, comprising 7 men and 1 woman with mean age of 18.6 years. Arthroscopy revealed multiple longitudinal tears in 2 patients, longitudinal tear in 2 patients, degenerative tear in 3 patients, and flap tear in 1 patient. Two patients were treated by repair, five by partial excision, and one by rasping only. The mean Lysholm score was 65 before surgery and recovered to 89 at the last followup, on average 12 months after surgery. Anterior horn tear of the lateral meniscus in footballers with a stable knee is characterized by pain at the anterolateral aspect of the knee during knee extension, especially when kicking a ball, and pain during weight-bearing knee extension, together with MRI finding of hyperintense signal in the anterior horn of the lateral meniscus. Preoperative diagnosis may be possible based on these findings in footballers. PMID- 22084744 TI - Transanal resection of rectal lipoma mimicking rectal prolapse: description of a case and review of the literature. AB - Submucosal lipomas of the large bowel are uncommon. Occasionally, they occur in the rectum and may cause aspecific symptoms; presentation with rectal prolapse is very unusual and may lead to a misdiagnosis of simple mucosal prolapse. The paper describes an additional case of a prolapsing rectal mass that led to diagnosis and surgical treatment of a rectal lipoma under local anesthesia. PMID- 22084746 TI - Synchronous Laparoscopic Radical Nephrectomy Left and Contralateral Right Hemicolectomy during the Same Endoscopic Procedure. AB - Synchronous renal cell carcinoma in patients with colorectal carcinoma is reported in various percentages ranging from 0.03 up to 4.85% (Halak et al. (2000), Capra et al. (2003)). When surgical treatment is indicated usually two separate operations are planned for resection. In open surgery, in such cases simultaneous resection is recommended if possible. Few reports have described the resection of colorectal and renal cell carcinoma in a single laparoscopic procedure. We have shown that combining left radical nephrectomy and right hemicolectomy is technically feasible, safe and that overall operative time can be limited. In our case operative time was 210 minutes, blood loss 100 milliliters, and duration of hospital stay was 8 days. Adequate port placement, preoperative scheduling, and surgical experience are essential to achieve this goal. PMID- 22084747 TI - Two unusual gastrointestinal foreign bodies. AB - Swallowed foreign bodies are common in the pediatric age group, but fortunately, the majority of them pass spontaneously without any adverse effects. Tube gastrostomy is an excellent method to provide prolonged enteral feeding. It is, however, associated with complications, namely, intraperitoneal leak and distal migration of the gastrostomy tube causing gastric outlet obstruction. This paper describes two unusual gastrointestinal foreign bodies, one was swallowed, while the other one was a complication of a tube gastrostomy. PMID- 22084748 TI - Dystonia and the role of deep brain stimulation. AB - Dystonia is a painful, disabling disease whose cause in many cases remains unknown. It has historically been treated with a variety methodologies including baclofen pumps, Botox injection, peripheral denervation, and stereotactic surgery. Deep brain stimulation (DBS) is emerging as a viable treatment option for selected patients with dystonia. Results of DBS for dystonia appear to be more consistently superior in patients with primary versus secondary forms of the disorder. Patients with secondary dystonia, due to a variety of causes, may still be candidates for DBS surgery, although the results may not be as consistently good. The procedure is relatively safe with a small likelihood of morbidity and mortality. A randomized trial is needed to determine who are the best patients and when it is best to proceed with surgery. PMID- 22084750 TI - Emergency pancreaticoduodenectomy in duodenal paraganglioma: case report. AB - Duodenal gangliocytic paraganglioma (DGP) is a rare tumor that characteristically occurs in the second part of duodenum. These appear as submucosal masses that protrude into the lumen of a duodenum. Gastrointestinal bleeding is the commonest manifestation of DGP. Metastatic spread to regional lymph nodes occurs rarely. Surgical resection is the treatment of choice for DGP. A case of a DGP is reported in young female who presented with a recurrent upper gastrointestinal bleeding. Upper gastrointestinal endoscopy (UGIE) documented a mass in the ampullary region with ulceration in its middle which was bleeding. Recurrent gastrointestinal bleeding necessitated an emergency pancreaticoduodenectomy. Histopathology of specimen documented gangliocytic paraganglioma. PMID- 22084749 TI - Surgical brain metastases: management and outcome related to prognostic indexes: a critical review of a ten-year series. AB - Brain metastasis are the most common neoplastic lesions of the nervous system. Many cancer patients are diagnosed on the basis of a first clinical presentation of cancer on the basis of a single or multiple brain lesions. Brain metastases are manifestations of primary disease progression and often determine a poor prognosis. Not all patients with a brain metastases undergo surgery: many are submitted to alternative or palliative treatments. Management of patients with brain metastases is still controversial, and many studies have been developed to determine which is the best therapy. Furthermore, management of patients operated for a brain metastasis is often difficult. Chemotherapy, stereotactic radiosurgery, panencephalic radiation therapy, and surgery, in combination or alone, are the means most commonly used. We report our experience in the management of a ten-year series of surgical brain metastasis and discuss our results in the preoperative and postoperative management of this complex condition. PMID- 22084752 TI - A rare presentation of pellet injury in the neck. AB - Penetrating neck injuries are dangerous and deserve emergency treatment by virtue of the vital structures present underneath. There is a potential risk of unrecognized vascular injury and retained foreign bodies with their associated complications in these wounds. Therefore, an early diagnostic workup to localize the site of injury and an immediate neck exploration are important. PMID- 22084751 TI - Cerebral melanoma metastases: a critical review on diagnostic methods and therapeutic options. AB - Malignant melanoma represents the third most common cause for cerebral metastases after breast and lung cancer. Central nervous system (CNS) metastases occur in 10 to 40% of patients with melanoma. Most of the symptoms of CNS melanoma metastases are unspecific and depend on localization of the lesion. All patients with new neurological signs and a previous primary melanoma lesion must be investigated. Although primary diagnosis may rely on computed tomography scan, magnetic resonance images are usually used in order to study more precisely the characteristics of the lesions in and to embase the surgical plan. Other possible complementary exams are: positron emission tomography, iofetamine cintilography, immunohistochemistry of liquor, monoclonal antibody immunocytology, optical coherence tomography, and transcriptase-polymerase chain reaction. Treatment procedures are indicated based on patient clinical status, presence of unique or multiple lesions, and family agreement. Often surgery, radiosurgery, whole brain radiotherapy, and chemotherapy are combined in order to obtain longer remissions and optimal symptom relieve. Corticoids may be also useful in those cases that present with remarkable peritumoral edema and important mass effect. Despite of the advance in therapeutic options, prognosis for patients with melanoma brain metastases remains poor with a median survival time of six months after diagnosis. PMID- 22084753 TI - Ectopic sequestered thyroid tissue: an unusual cause of a mediastinal mass. AB - An 80-year-old female presented with an incidental finding of a retrosternal mass on magnetic resonance imaging. Ultrasound demonstrated a mediastinal lesion adjacent to but separate from the inferior pole of the right thyroid lobe. Fine needle aspiration cytology demonstrated colloid and follicular cells. At surgery, the right thyroid lobe was found to be normal. A discrete 5 cm nodule was found in the anterior mediastinum separate from the thyroid and just anterior and to the right of the trachea and thymus. The nodule had a vascular pedicle arising from the mediastinum. The differential diagnosis included metastatic thyroid carcinoma. Histology was consistent with a benign ectopic sequestered thyroid nodule. Extensive investigations demonstrated no sign of a thyroid malignancy. PMID- 22084754 TI - The results of vascular and biliary variations in turks liver donors: comparison with others. AB - Objective. To evaluate liver anatomy with a view to access unerring surgery in liver donors. Summary Background Data. Liver transplantation, the unique curative treatment option for end-stage hepatic failure, has become routinely practicable, which was inconceivable in the past. But, the vascular and biliary anatomy of the liver has not been completely disclosed yet. Methods. From 1994 to 2009, we have done a research on 496 liver donors. The data were accumulated and categorized according to the most widely used classification systems. Results. Of 496 liver donors, 393 (79.1%) underwent the right donor hepatectomy, 98 (19.9%) were performed the left lateral segmentectomy, and 5 donors (1%) underwent the left donor hepatectomy surgery. Given the data regarding to 398 liver donors undergone right and left donor hepatectomy, arteries, bile ducts, and portal vein showed classical anatomy in 107 (21.6%) donors. Variations in all three systems were found in 16 donors (3.2%). In the remaining 275 donors (75.2%), anatomical variations were found at either of arterial, biliary, or portal system. Conclusions. Our study could come up to actual estimate in liver anatomy as any of donors have not been removed in our institute due to high hilar dissection technique. PMID- 22084755 TI - Arthroscopic treatment of stiff elbow. AB - Contracture of the elbow represents a disabling condition that can impair a person's quality of life. Regardless of the event that causes an elbow contracture, the conservative or surgical treatment is usually considered technically difficult and associated with complications. When the conservative treatment fails to restore an acceptable range of motion in the elbow, open techniques have been shown to be successful options. More recently the use of arthroscopy has become more popular for several reasons. These reasons include better visualization of intra-articular structures, less tissue trauma from open incisions, and potentially the ability to begin early postoperative motion. The purpose of this paper is to review the indications, complications, and results of arthroscopic management of a stiff elbow. PMID- 22084756 TI - Giant splenic artery aneurysm: case report. AB - Splenic artery aneurysm is the third most common location of intra-abdominal aneurysms. Giant splenic artery aneurysm is rarely seen and is at a high risk of rupture. Location and size of the splenic artery aneurysm determine the likelihood of rupture. A case of giant splenic artery aneurysm in a 35-year-old woman is reported. She presented with upper gastrointestinal bleeding. She had splenomegaly and extrahepatic hepatic portal hypertension. Angiography confirmed a giant splenic artery aneurysm measuring 8 * 10 centimeters, located in middle and distal two-thirds of the splenic artery. Surgical treatment in the form of in toto excision of aneurysm with splenectomy and devascularization was performed. PMID- 22084757 TI - Pilot study on the efficiency of the biostimulation with autologous plasma rich in platelet growth factors in otorhinolaryngology: otologic surgery (tympanoplasty type I). AB - When otologic procedures that involve tympanic membrane repairs are performed, biomaterials or biological tissues as normal as grafts are used. At the moment, biological material from the own patient is used with varying success rates. The procedure used and the patient's tissue repair capabilities tend to determine the outcome. We present a preliminary study on tympanic membrane perforation repairs using an autograft obtained by manipulating platelet degranulation and the coagulation cascade and reinforced with a seal using platelet growth factors. We present three cases in which we used this procedure. The results will be valued based on the tympanic perforation closure index. With this study, we want to assess the effectiveness of tympanic perforation repairs with this technically simple method. If this method was objectively proved to be effective, it would lead to lower patient morbidity and sanitary costs. PMID- 22084758 TI - Strangulated tension viscerothorax with gangrene of the stomach in missed traumatic diaphragmatic rupture. AB - Acquired diaphragmatic hernias are usually posttraumatic in occurrence. In patients who have blunt trauma and associated diaphragmatic hernia, the diagnosis may be missed or delayed, often leading to poor treatment outcomes. We present a rare occurrence of tension viscerothorax due to missed traumatic diaphragmatic rupture in a 25-year-old woman whose condition was complicated by gangrene and perforation of the fundus as well as questionable viability of the anterior wall of the body of the stomach. The patient had a successful emergency transabdominal suture plication of the diaphragm and gastroplasty and has remained symptomless 3 months postoperatively. PMID- 22084759 TI - A review of posttraumatic bowel injuries in ibadan. AB - Background. Bowel injuries are a leading cause of morbidity and mortality following trauma. Evaluating patients who sustained abdominal trauma with bowel injury may pose a significant diagnostic challenge to the surgeon. Prompt recognition and timely intervention is necessary to improve outcome. Aim. This study was undertaken to evaluate treatment and outcome of patients with bowel trauma. Methods. A 5-year retrospective study of all patients presenting with abdominal trauma requiring surgical intervention seen in the UCH Ibadan, Nigeria was undertaken. Results. There were 71 patients (59 males and 12 females). The majority of cases (70%) occurred between the 3rd and 5th decades of life. Some 37 patients (52%) sustained blunt abdominal injury, while 34 patients (48%) sustained penetrating abdominal injury. There were 27 patients with bowel injuries (38%). Isolated bowel injuries occurred in 19 patients (27%). The most common surgical operation performed was simple closure. There were 3 deaths in patients with bowel injuries. Conclusion. Most cases of bowel injury can be managed by simple closure, a technique that is not so technically demanding for surgeons in less-developed countries. This study has also incidentally identified a "rule of six" for patients with bowel injuries and abdominal trauma. PMID- 22084760 TI - Simultaneous use of cannulated reamer and schanz screw for closed intramedullary femoral nailing. AB - Introduction. Closed reduction is a critical component of the intramedullary nailing and at times can be difficult and technically challenging resulting in increased operative time. Fluoroscopy is used extensively to achieve closed reduction which increases the intra-operative radiation exposure. Materials and Methods. Sixty patients with femoral diaphyseal fractures treated by locked intramedullary nailing were randomized in two groups. In group I, fracture reduction was performed under fluoroscopy with a cannulated reamer in the proximal fragment or with simultaneous use of a cannulated reamer in the proximal fragment and a Schanz screw in the distal fragment. Patients in group II had fracture reduction under fluoroscopy alone. Results. Closed reduction was achieved in 29 patients in group I and 25 patients in group II. The guide wire insertion time, time for nail insertion and its distal locking, total operative time, and total fluoroscopic time were 26.57, 27.93, 68.03, and 0.19 minutes in group I, compared with 30.87, 27.83, 69.93, and 0.24 minutes in group II, respectively. The average number of images taken to achieve guide wire insertion, for nail insertion and its locking and for the complete procedure in group I, respectively, was 12.33, 25.27, and 37.6 compared with 22.1, 26.17, and 48.27, respectively, in group II. Conclusion. The use of cannulated reamer in proximal fragment as intramedullary joystick and Schanz screw and in the distal fragment as percutaneous joystick facilitates closed reduction of the fracture during closed intramedullary femoral nailing with statistically significant reduction in guide wire insertion time and radiation exposure. PMID- 22084761 TI - Collateral tissue damage by several types of coagulation (monopolar, bipolar, cold plasma and ultrasonic) in a minimally invasive, perfused liver model. AB - Hemostasis in minimally invasive surgery causes tissue damage. Regardless of the method of production of thermal energy, a quick and safe coagulation is essential for its clinical use. In this study we examined the tissue damage in the isolated perfused pig liver using monopolar, bipolar, cold plasma, and ultrasonic coagulation. In a minimally invasive in vitro setup, a 2-3 cm slice of the edge of the perfused pig liver was resected. After hemostasis was achieved, liver tissue of the coagulated area was given to histopathological examination. The depth of tissue necrosis, the height of tissue loss, and the time until sufficient hemostasis was reached were analyzed. The lowest risk for extensive tissue damage could be shown for the bipolar technique, combined with the highest efficiency in hemostasis. Using cold plasma, coagulation time was longer with a deeper tissue damage. Monopolar technique showed the worst results with the highest tissue damage and a long coagulation time. Ultrasonic coagulation was not useful for coagulation of large bleeding areas. In summary, bipolar technique led to less tissue damage and best coagulation results in our minimally invasive model. These results could be important to recommend bipolar coagulation for clinical use in minimally invasive surgery. PMID- 22084762 TI - Malignant peripheral nerve sheath tumors in Africa: a clinicopathological study. AB - Introduction. Malignant peripheral nerve sheath tumors (MPNSTs) are rare, aggressive soft tissue sarcomas associated with poor prognosis, that most commonly affect patients aged 20 to 50 years, but have also been reported in children. There is little reported in literature on these tumors in Africa. Materials and Methods. A search of the hospital pathology database between 1992 and 2008 revealed 333 nerve sheath tumors, of which 31 were MPNSTs. Four representative case reports are presented. Discussion. MNPSTs have rarely been reported from sub-Saharan Africa; in this study, they constituted 9.3% of all nerve sheath tumors. The trunk (42%) and limbs (45%) were the most frequently affected anatomical sites. Late presentation of malignant lesions in this environment is exemplified by the four case presentations patients. Conclusions. This report confirms observations from studies on MPNSTs from other environments. Anatomically centrally located MPNSTs may have a higher incidence in sub-Saharan Africa than in the West. Because NF1-associated MPNSTs are difficult to diagnose clinically, and because surgery is the only mode of therapy that offers a complete cure, a lifetime follow-up is important, as this would enable diagnosis of early lesions amenable to surgical extirpation. PMID- 22084763 TI - Secondary tuberculosis of breast: case report. AB - Tuberculosis of breast is a rare disease which is difficult to differentiate from carcinoma of breast. The involvement of breast can be primary or secondary to some focus in body. A case of secondary tuberculosis of right breast in a 21-year old female from Kashmir, India, is being reported. Presentation was as a painless discharging sinus of right breast. A tubercular foci of rib was the affecting source of disease. No other evidence of tuberculosis was present in the body. Resection of involved rib segment, along with the discharging sinus, was performed. The patient had antitubercular therapy for 9 months, with no recurrence seen in followup. PMID- 22084764 TI - Adjuvant perioperative intraperitoneal chemotherapy in locally advanced colorectal carcinoma: preliminary results. AB - Background and Aims. Intraperitoneal chemotherapy is a basic tool in the treatment of peritoneal malignancy. The purpose of the study is to investigate the effect of adjuvant perioperative intraperitoneal chemotherapy in the treatment of locally advanced colorectal cancer. Patients and Methods. Patients with T(3) and T(4) colorectal carcinomas that underwent R(0) resection received either hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC group = 40 patients) or early postoperative intraperitoneal chemotherapy (EPIC group = 67 patients). The survival, the recurrences and the sites of recurrence were assessed. Results. The 3-year survival rate for HIPEC group was 100% and for EPIC group 69% (P = .011). Nodal infiltration was found to be the single prognostic indicator of survival. The incidence of recurrence in EPIC group was higher than in HIPEC group (P = .009). The independent indicators of recurrence were the use of HIPEC and the degree of differentiation (P < .05). Conclusions. Intraperitoneal chemotherapy, particularly HIPEC, as an adjuvant in locally advanced colorectal carcinomas appears to improve survival and decrease the incidence of recurrence. PMID- 22084765 TI - Alimentation impact of treatments of 254 oropharyngeal cancers (1998-2003). AB - Objective. To analyze the functional impact of the various possible treatments of oropharyngeal squamous cell carcinomas to find the main prognostic factors of dysphagia induced by these treatments. Patients. Clinical data from 254 patients treated for squamous cell carcinoma of the oropharynx between 1998 and 2003 were retrospectively analyzed. A multivariate model enabled us to evaluate the role of each potentially harmful factor on swallowing. Main Outcome Measures. The significant factors influencing the consumption of liquid, pasty, and normal food were the same: the initial T stage and the type of treatment. Conclusion. Whatever the possible and selected treatment was, the impact on the functional capacities, and thus, the quality of life of the patients was considerable. Even though we could not significantly demonstrate exclusive radiotherapy caused more long-term undesirable effects than surgery followed by radiotherapy, our daily practice has shown that we should favour the latter. PMID- 22084766 TI - Spontaneous Hepatic Rupture with Intraperitoneal Hemorrhage without Underlying Etiology: A Report of Two Cases. AB - Spontaneous hepatic rupture is a rare event most often occurring in association with underlying liver disease or pregnancy. We report two unusual cases of hepatic rupture without any identifiable pathology, trauma, or comorbid conditions. PMID- 22084767 TI - Perils of prolonged impaction of oesophageal foreign bodies. AB - Ill-conceived effort at removal of impacted foreign bodies (FBs) in oesophagus vies with delay in removal as the causes of morbidity and mortality. Most oesophageal FBs are safely removed endoscopically when attempted early. However, large sharp FBs like dentures and meat bones can get deeply embedded in the wall with prolonged impaction or injudicious attempts at removal leading to life threatening mediastinitis. Open surgery to access the oesophageal-impacted FB in such an event is hazardous. This report emphasizes the need for early site specific surgical approaches that may be required, albeit rarely, for oesophageal impacted FBs, where attempts at endoscopic removal have failed or complications have ensued. PMID- 22084768 TI - Treatment of complex fistula in ano with cable-tie seton: a prospective case series. AB - Objective. To determine the fecal incontinence and recurrence rate in patients with complex fistula in ano managed with cable tie seton at a tertiary care teaching hospital. Methods. This is a prospective case series of patients with complex anal fistula i.e. recurrent fistula or encircling >30% of external anal sphincter, managed with cable tie seton from March 2003 to March 2009. Patients were seen in the clinic after 72 hours of seton insertion under anesthesia and then every other week. Each time the cable-tie was tightened if found loose without anesthesia and incontinence was inquired according to wexner's score. Results. Seventy nine patients were treated during the study period with the age (mean +/- standard deviation) of 41 +/- 10.6 years and. The seton was tightened with a median of six times (3-15 times range). Complete healing was achieved in 11.2 +/- 5.7 weeks. All the patients were followed for a minimum period of one year and none of the patients had any incontinence. Recurrence was found in 4 (5%) patients. Conclusion. The cable tie seton is safe, cost effective and low morbidity option for the treatment of complex fistulae-in-ano. It can, therefore, be recommended as the standard of treatment for complex fistulae-in-ano requiring the placement of a seton. PMID- 22084769 TI - Adhesive intestinal obstruction in infants and children: the place of conservative treatment. AB - Objectives. Adhesive intestinal obstruction (AIO) is rare in the pediatric age group and its treatment is still controversial. This is a retrospective review of our experience in infants and children with AIO. Patients and Methods. The records of infants and children with AIO between January 2001 and December 2010 were retrospectively reviewed for age at diagnosis, sex, initial operation, interval between initial operation and presentation, diagnosis, treatment and outcome. Results. 44 infants and children were admitted with AIO. There were 28 males and 16 females who had 46 episodes. Their ages at presentation ranged from 1 month to 12 years (mean 5.4 years), while their ages at initial operation ranged from 2 days to 12 years (mean 4.15 years). Time elapsed from initial operation to presentation ranged from 7 days to 8 years (mean 1.5 years), and 66% developed AIO within 1 year from initial operation. Appenedecectomy was the commonest operation (29.5%). Four (9%) responded to conservative treatment. The other 40 (91%) required surgical intervention. Twenty-nine had release of adhesions only, while 10 (25%) had resection of small intestines and one underwent stricturoplasty. Two developed recurrence and one died. Conclusions. AIO is rare in the pediatric age group and the majority becomes symptomatic within 1 year of operation. Appendecectomy is the commonest operation leading to AIO. The place of conservative treatment is limited and to obviate delay and decrease the chance of intestinal ischemia, they should be treated early with surgical adhesiolysis. PMID- 22084770 TI - Transient myocarditis associated with fulminant colitis. AB - Case Summary. An 18-year old man presented with a three-week history of abdominal pain, weight loss and bloody diarrhoea. He was profoundly septic, with generalised abdominal tenderness. CT and flexible sigmoidosopy confirmed colitis of the colon with rectal sparing. Laparotomy was performed when conservative management failed to improve his condition. Subtotal colectomy, with end ileostomy and mucus fistula formation, was performed in light of active colitis. Despite successful operative intervention the patient acute left ventricular failure, raising the possibility of giant cell myocarditis, which fully resolved before a definitive diagnosis could be reached. Discussion. It is possible that the transient cardiac failure in this case may represent an overwhelming inflammatory response or myocarditis. Inflammatory bowel disease is rarely associated with giant cell myocarditis (GCM). GCM usually affects a young population and its prognosis is variable, ranging from complete recovery, remission with recurrence and fatality. The management of this group of patients is still relatively experimental. Conclusion. Fulminant colitis can be associated with a rapid deterioration in cardiac function. Causes include sepsis, systemic inflammatory response syndrome or myocarditis. GCM should be considered in patients with new onset of left ventricular failure that decline rapidly. PMID- 22084771 TI - Prediction of length of stay following elective percutaneous coronary intervention. AB - There have been published risk stratification approaches to predict complications following percutaneous coronary interventions (PCI). However, a formal assessment of such approaches with respect to predicting length of stay (LOS) is lacking. Therefore, we sought to assess the performance of, an easy-to-use, tree structured prognostic classification model in predicting LOS among patients with elective PCI. The study is based on the New York State PCI database. The model was developed on data for 1999-2000, consisting of 67,766 procedures. Validation was carried out, with respect to LOS, using data for 2001-2002, consisting of 79,545 procedures. The risk groups identified by the model exhibited a strong progressively increasing relative risk pattern of longer LOS. The predicted average LOS ranged from 3 to 9 days. The performance of this model was comparable to other published risk scores. In conclusion, the tree-structured prognostic classification is a model which can be easily applied to aid practitioners early on in their decision process regarding the need for extra resources required for the management of more complicated patients following PCI, or to justify to payors the extra costs required for the management of patients who have required extended observation and care after PCI. PMID- 22084772 TI - A systematic and evidence-based approach to the management of vertebral metastasis. AB - Diagnosis and management of vertebral metastasis requires a systematic approach to patient identification as well as selection of appropriate therapy. Rapid identification and prompt intervention in the treatment of malignant epidural spinal cord compression (MESCC) is key to maintaining quality of life. This paper provides a series of tools as well as guidance in selecting effective and evidence-based therapy individualized to the specific patient. PMID- 22084773 TI - Diagnostic accuracy of fine needle aspiration cytology in parotid lesions. AB - Objective. Histopathology of parotid gland tumors is extremely varied and complex due to heterogeneous cellular composition. Preoperative diagnostic tools include fine needle aspiration cytology, the role of which remains controversial. The aim of this paper is to evaluate the usefulness and accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of parotid gland tumors. Methods. We retrospectively reviewed charts of 129 patients who underwent parotidectomy for parotid lesions at Aga Khan University Hospital from 2002 to 2010. We compared the results of preoperative FNAC with final histopathological diagnosis. Results. Concordance with histological results was observed in 86%, specificity was 98%, sensitivity was 84%, and diagnostic accuracy was 94%. Conclusion. Our results demonstrate that preoperative cytology in parotid lesions is fairly accurate and useful in diagnosing benign from malignant and in planning appropriate approach for treatment. PMID- 22084774 TI - Trocar site hernia after laparoscopic colectomy: a case report and literature review. AB - Background. Trocar Site Hernia (TSH) is defined as an incisional hernia which occurs after minimally invasive surgery on the trocar incision site.In 2004 Tonouchi classified trocar site hernias into 3 types: Early onset type; Late onset type; Special type. Case Report. We report the case of a 76-year old woman that underwent an emergency explorative laparotomy on the 10th p.o. day after a laparoscopic left hemicolectomy. Surgery showed a small bowel herniation through the 12 mm trocar incision site; the intestinal loop appeared necrotic and had to be resected, and the hernia orifice was repaired. We carried out a review of literature about this topic. Discussion. The clinical onset of a trocar site hernia is usually early, occurring within the 30th post operative day and it is caused by the omentum or small bowel entrapment into the trocar orifice. The clinical presentation is insidious, with progression to an acute abdomen, and an emergency surgical approach is often required. Conclusions. TSH is a severe complication of operative laparoscopy especially with large-bore trocar ports. The incidence of TSH resulting from our review ranges from 0.007% to 22% with an average of 1.85%. Prevention of TSH appears to be more effective when trocar insertion through the abdominal wall is tangential, the closure of both the fascia and the peritoneum is performed if the incision is greater than 7 mm, the suture of extra umbilical port site is performed under laparoscopic vision. PMID- 22084775 TI - Patient demographics in acute care surgery at the ruijin hospital in shanghai. AB - Acute Care Surgery is a discipline that includes trauma care, surgical critical care, and emergency surgery. It is organized in different models and provides mainly operative and nonoperative care. The aim of this study was to provide a demographic analysis of the care of surgical patients at the Emergency Department (ED) in a large teaching hospital in Shanghai, where general surgeons and orthopedic surgeons take care for most of all acute surgery. A bilingual questionnaire was developed to collect data for patients referred to the general or orthopedic surgeon in the ED (June-September 2008). Data about the gender, age, diagnosis, diagnostic tools, treatments, and outcomes were collected. A total of 255 questionnaires were collected; the most common diagnoses of patients were infections of abdominal organs and fractures. Complementary diagnostics like X-ray (59%), blood tests (36%), and ultrasound (17%) were frequently used. More than half of the patients were discharged afterwards most of them with followup. This study gives a first overview of acute care surgery of the emergency patients of the ED in a large Chinese metropolitan hospital. PMID- 22084776 TI - Dysphagia lusoria: a case of an aberrant right subclavian artery and a bicarotid trunk. AB - Dysphagia Lusoria is dysphagia secondary to an aberrant right subclavian artery that has a retroesophageal course. Adachi and Williams categorized aortic arch anomalies, showing that the right subclavian artery arising in this fashion (as the final branch of the descending aortic arch) is one of the more common. However, this very rarely coexists with a bicarotid trunk. We present such a case as it is manifested in a 36-year-old lady complaining of marked weight loss and dysphagia. The diagnosis remained elusive until a CT scan of the chest was performed; angiography further delineated the pathology. It is believed that the combination of the common carotid origins with the retroesophageal course of the aberrant vessel more frequently accounts for symptoms in the absence of an aneurysm of the origin of the aberrant vessel. Several techniques to manage the aberrant vessel have been described in the literature, but we favoured open ligation and transposition to the right carotid artery. PMID- 22084777 TI - Reconsideration of laparoscopic cholecystectomy. AB - We describe the surgical method of cases showing a distended gallbladder. Because the most important thing does not cause biliary tract injury, it is to find orientation carefully. The frequency of incidental gallbladder cancer was in 7 (0.7%) of the 983. Only cholecystectomy is necessary to be performed for Tis or T1 cancer, and surgery has to be changed to radical surgery for T2 cancer or deeper invasion. Laparoscopic cholecystectomy is already an established standard operation. In the presence of acute or severe chronic inflammation, special attention should be paid to these points. PMID- 22084778 TI - Small bowel obstruction caused by an incarcerated hernia after iliac crest bone harvest. AB - The iliac crest has become an often used site for autogenous bone graft, because of the easy access it affords. One of the less common complications that can occur after removal is a graft-site hernia. It was first reported in 1945 (see the work by Oldfield, 1945). We report a case of iliac crest bone hernia in a 53 year-old male who was admitted for elective resection of a pseudarthrosis and reconstruction of the left femur with iliac crest bone from the right side. One and a half months after initial surgery, the patient presented with increasing abdominal pain and signs of bowel obstruction. A CT scan of the abdominal cavity showed an obstruction of the small bowel caused by the bone defect of the right iliac crest. A laparoscopy showed a herniation of the small bowel. Due to collateral vessels of the peritoneum caused by portal hypertension, an IPOM (intraperitoneal onlay-mesh) occlusion could not be performed. We performed a conventional ventral hernia repair with an onlay mesh. The recovery was uneventful. PMID- 22084779 TI - Recurrent chest pain, as a presenting sign of ovarian endometrioma. AB - Chest pain is a rare sign of thoracal endometriosis associated with endometrioma of the tubo-ovarian endometrioma. We report the case periodic episodes of chest pain concurrent with menstruation in a 35-year-old female, in which ovarian endometrioma was diagnosed and left-sided oophorectomy was performed. After surgery, patient underwent medical treatment which included a Gn-RH agonist and a combined oral contraceptive. In the follow-up period, there was no evidence of chest pain. PMID- 22084780 TI - Acute posterior shoulder dislocation with reverse hill-sachs lesion of the epiphyseal humeral head. AB - Posterior dislocation of the shoulder is an unfrequent event that often occurs as a consequence of a direct trauma or epileptic crisis. Frequently the posterior dislocations are misunderstood, so they become chronic lesions. We reported a case of an acute posterior left shoulder dislocation with lesser tuberosity fracture and reverse Hill-Sachs lesions which involved more than 25% of the articular surface of the humeral head, in a 57-old-year man with right hemiparesis. We performed a synthesis of the lesser tuberosity with a screw, and we restored the shape of the humeral head with allograft. We achieved a good result that allows the patient to be able to do his previous activities of daily living. PMID- 22084781 TI - Treatment of maxillary deficiency by miniplates: a case report. AB - Introduction. Numerous devices have been introduced for correction of Class III malocclusion and maxillary deficiency. Aim. To assess the dentoskeletal effects of miniplates combined with Class III traction in treating Cl III malocclusion and maxillary deficiency in growing patients. Methods. This case describes the treatment of a maxillary-deficient 11-year-old boy by using miniplates. The patient's parents rejected the use of extraoral appliances and major surgical correction; therefore the treatment was done by using Class III elastics connected from two mandibular miniplates to an upper removable appliance. Two miniplates were inserted in the anterior part of the mandible in the canine areas under local anaesthesia. The treatment lasted for 10 months after which favourable correction of the malocclusion was observed. Results. The SNA and ANB angles increased by 5.1 degrees and 4.4 degrees , respectively. Lower 1 to mandibular plane decreased by 3.4 degrees . Conclusions. This case demonstrates that miniplates can be a suitable method to extraoral appliances and major surgery in maxillary deficiency cases. PMID- 22084782 TI - Congenital paraesophageal hernia with intrathoracic gastric volvolus in two sisters. AB - Congenital paraesophageal hernia is rare in infants and children. This paper describes our experience with seven infants and children with congenital paraesophageal hernia with emphasis on two sisters who presented with unusually large paraesophageal hernias and herniation of most of the stomach resulting in intrathoracic gastric volvolus. The literature on the subject is also reviewed. PMID- 22084783 TI - Aggressive surgical treatment in late-diagnosed esophageal perforation: a report of 11 cases. AB - Introduction. Esophageal perforation is a relatively uncommon and lethal disease usually resulting from endoscopic procedures. Delay in the diagnosis and treatment occurs in more than 50% of cases, leading to a mortality rate of 40% to 60%, but this rate decreases is 10%-25% if treatment is carried out within 24 hours of perforation. Case Presentation. To analyze the characteristics, etiology, site of perforation, presentation, time interval till diagnosis, treatment and outcome of patients with esophageal perforation. Over a five-year period, from October 2004 through March 2009, 11 patients with esophageal perforation were referred to the division of thoracic surgery of a tertiary referral hospital. In eight patients, perforations were thoracic with delayed diagnosis for at least 48 hours. Two patients had cervical esophageal perforation, and one patient had early-diagnosed Boerhaave's syndrome. Eight patients are alive after followup for a period ranging from eight months to five years. In the remaining three patients, cancer was the underlying disease and the reason of death. Conclusion. No patient with esophageal perforation should be deprived from surgical repair due to delayed diagnosis. All, except preterminal patients, should undergo exploration after resuscitation, and appropriate treatment should be carried out depending on the findings during operation. Aggressive treatment is necessary in the case of established mediastinitis. PMID- 22084784 TI - Using nodal ratios to predict risk of regional recurrences in patients treated with breast conservation therapy with 4 or more positive lymph nodes. AB - Purpose. The value of nodal ratios (NRs) as a prognostic variable in breast cancer is continually being demonstrated. The purpose of this study was to use NR in patients with >=4+ nodes to assess a correlation of NR with regional (lymph node) recurrence. Methods. Inclusion criteria was >=8 nodes dissected with >=4+ nodes after breast conservation therapy. Of 1060 patients treated from 1975 to 2003 who had a minimum of 8 nodes dissected, 273 were node+; 56 patients had >=4+ involved nodes and were the focus of this study. Nodal ratios were calculated for each patient and grouped into 3 categories: high (>=70%), intermediate (40%-69%) and low (<40%). Each nodal ratio was correlated with patterns of local, regional, and distant failures and OS. Results. Outcomes for the entire cohort were BRFS 83%, NRFS-93%, DMFS-61%, and OS 63% at 10 yrs. The OS, DMFS, and NRFS correlated with N2 (4-9 nodes+) versus N3 (>=10+) status but did not correlate with BRFS, as expected. When evaluating NR, 18 pts had high NR (>70%). Only 3 patients experienced nodal recurrences, all within previously radiated supraclavicular fields. All 3 in-field regional failures occurred in the N3 group of patients with NR >70%. All were treated with a single AP field prescribed to a dose of 46 Gy at a standard depth of 3 cm. Conclusions. In this group of N2/N3 patients treated with BCT, we were able to identify patients at high risk for regional failures as those with high NR of >70% and >=10+ nodes. While these findings need to be reproduced in larger datasets, this group of patients with NR of >70% in 4 or more positive axillary lymph nodes may benefit from meticulous targeting of regional nodes, dose escalation, and/or more intensive systemic therapies. PMID- 22084786 TI - Diffuse cutaneous metastases as the only sign of extranodal tumor spread in a patient with adenocarcinoma of the colon. AB - Cutaneous metastases from large bowel cancer are uncommon and are usually associated with organ involvement. Localization of lesions to the skin is mainly attributed to vascular and anatomical relationship, since most of them are seen in the abdominal wall or in a surgical scar. We report a 73-year-old woman in whom metastatic nodules from a poorly differentiated adenocarcinoma of the right colon developed throughout the skin (buttock, trunk, chest wall, arms, and neck) and remained the only sign of extranodal tumor spread until patient's death, seven months later. This unusual behaviour suggests that localization of neoplastic cells to the skin may be a site-specific process, determined by adhesion molecules and/or by growth factors found at that site. PMID- 22084785 TI - Giant gastrointestinal stromal tumor presenting as a palpable abdominal mass: an unusual presentation. AB - Gastrointestinal stromal tumors (GIST-) account for the majority of mesenchymal tumors arising within the gastrointestinal tract. GIST presenting as a palpable abdominal mass is extremely rare. We report four additional cases of a GIST presenting as an abdominal mass along with a pertinent review of the literature. Twenty five cases of GISTs presenting with an abdominal mass, including 4 cases discussed here, have been reported in the world literature since 2001. The mean duration of symptoms was 152.7 days. Twenty one of 25 (84%) patients received surgical resection. The mean tumor size was 17.2 cm, with an average mitotic index of 7.6 per 50 high power fields. Thirteen of 14 (92.9%) patients had a high risk tumor. Five patients were disease-free at a mean followup of 11 months, 2 patients had stable disease and 2 patients had progressive disease, and one patient had a partial response. In conclusion, symptomatic patents have an increased incidence of high-risk tumors and metastases at presentation. Adjuvant therapy with imatinib improves disease-free survival in patients with large abdominal GIST tumors, but no change in overall survival was noted. Finally, GISTs should be considered in the differential diagnosis of an abdominal mass in an elderly patient. PMID- 22084787 TI - Randomized split-mouth study on postoperative effects of palmitoylethanolamide for impacted lower third molar surgery. AB - The aim of this study was to assess the efficacy of Normast 300 mg in reducing swelling and pain after the surgical extraction of impacted lower third molars. Materials and Methods. A randomized, split-mouth, single-blind study was conducted on 30 patients between 18 and 30 years of age requiring lower third molar extraction. Patients underwent bilateral extractions in a randomized sequence, one extraction being performed under Normast treatment. The Normast treatment involved 2 tablets a day for 15 days. The parameters assessed at each procedure were trismus, swelling, pain, NSAID consumption, postoperative complications, drug tolerability, and safety. The results obtained were processed using repeated measures analysis of variance. Results. Perceived postoperative pain was reportedly significantly milder on Normast treatment than control. The trend of the means differed over time (P < .0001) and between the two extraction groups (P < .0221). On the other hand, for edema and trismus, the trend differed over time for both groups but did not differ between the two groups. Discussion. Our analyses indicate that patients experienced significantly less postoperative pain when they were treated with Normast. Conclusions. Administering Normast improves the postoperative course-in terms of pain-after lower third molar extraction. PMID- 22084788 TI - The management of "coats' response" in a patient with x-linked retinitis pigmentosa-a case report. AB - The management of exudative retinal detachment in Coats disease can be very difficult with variable results. A case is presented of a 12 year old boy who was diagnosed with X-linked retinitis pigmentosa with an associated "Coat's Response". The patient had a marked reduction in his left visual acuity due to intragel and subhyaloid haemorrhage as well as exudative retinal detachment. This was managed successfully with vitrectomy and endolaser, resulting in clearance of the haemorrhage and flattening of the retina. In our experience endolaser should be considered as viable therapeutic option in the management of this condition. PMID- 22084789 TI - Success rate of microimplants in a university orthodontic clinic. AB - Introduction. The purpose of this study was to examine the success rate and find factors affecting the clinical success of microimplants used as orthodontic anchorage. Methods. Seventy-three consecutive patients (25 male, 48 female; mean age, 22.45 years) with a total of 139 screw implants of 2 types were examined. Success rate was determined according to 18 clinical variables. Results. The overall success rate was 87.8%. The clinical variables of microimplant factors (type), patient factors (sex, skeletal and dental relationships, overbite, jaw involved, side involved and site involved), and treatment factors (type of insertion, time of loading, purpose of microimplant insertion, mode of loading, type of anchorage used, direction of forces applied) did not show any statistical difference in success rates. Mandibular angle, vertical position of implant placement, oral hygiene status, and inflammation showed significant difference in success rates. Conclusions. Proper case selection and following the recommended protocol are extremely essential to minimise failures. PMID- 22084790 TI - A rare case of recurrent hematuria from right kidney: radiologic diagnosis and treatment. AB - We report the case of a young woman admitted because of several and recurring episodes of macroscopic hematuria beginned after her first pregnancy. Contrast enhanced multidetector computed tomography images showed dilated ovarian veins due to a typical pelvic varicocele. We supposed to be a right ovarian vein syndrome, a rare clinical situation characterized by an anomalous compression of the lumbar ureter by the ectasic ovarian vein; this condition may cause a chronic inflammatory stimulus above the urothelial mucosa with a following hematuria. All symptoms were solved by an endovascular treatment through the sclero-embolisation of the pelvic varicocele. After eighteen months the patient didn't present hematuria anymore and she no longer complained about her right side lumbar pain. PMID- 22084791 TI - Robotic-assisted laparoscopic prostatectomy for high-risk prostate cancer: technical considerations and review of the literature. AB - Men with high-risk prostate cancer are at significant risk of progressive, symptomatic disease leading to metastases or death from prostate cancer. Surgery specifically robotic-assisted laparoscopic prostatectomy (RALP)-is increasingly being considered as a key component of a multimodal strategy to treat these patients. Herein, we review key technical considerations of performing RALP with bilateral pelvic lymphadenectomy in men with high-risk disease. Recent literature supporting the increasing role of surgery either alone or in combination with adjuvant therapies to treat men with high-risk prostate cancer is also reviewed. PMID- 22084792 TI - Endourological Management of Urolithiasis in Donor Kidneys prior to Renal Transplant. AB - Background. We present our centres successful endourological methodology of ex vivo ureteroscopy (EVFUS) in the management of these kidneys prior to renal transplantation. Patient and Methods. A retrospective analysis was performed of all living donors (n = 157) identified to have asymptomatic incidental renal calculi from January 2004 until December 2008. The incidence of asymptomatic renal calculi was 3.2% (n = 5). Donors were subdivided into 2 groups depending on whether theydonated the kidney with the renal calculus (Group 1) versus the opposite calculus-free kidney (Group 2). Results. All donors in Group 1 underwent a left laparoscopic donor nephrectomy. The calculi were extracted in all 3 cases using a 7.5 Fr flexible ureteroscope either prior to transplant (n = 2) or on revascularization (n = 1). There were no urological complications in either group. At a mean followup at 64 months there was no recurrent calculi formation in the recipient in Group 1. However, 1 recipient formed a calculus in group 2 at a follow up of 72 months. Conclusions. Renal calculi can be successfully retrieved during living-related transplantation at the time of transplant itself using EVUS. This is technically feasible and is associated with no compromise in ureteral integrity or renal allograft function. PMID- 22084793 TI - Giant Retroperitoneal Mucinous Tumor Supportively Diagnosed as a Dedifferentiated Liposarcoma by Fluorescence In Situ Hybridization of MDM2 Gene. AB - Surgical resection was performed on a 47-year-old woman for a retroperitoneal mass that weighed 8.5 kg. Histological examination revealed a myxoid sarcomatous tumor. Because diagnosis could not be determined by immunohistochemistry, attention was focused on MDM2 (murine double minute) gene amplification by fluorescence in situ hybridization (FISH) analysis. The tumor was finally determined to be a dedifferentiated liposarcoma. We experienced a case of a giant retroperitoneal dedifferentiated liposarcoma. FISH analysis was useful for the diagnosis and determination of the therapeutic strategy. PMID- 22084794 TI - Urinary Ascites following Mini Lap Tubectomy: A Rare Occurence. AB - Iatrogenic bladder injury is a known complication of laparoscopic and gynecological surgeries with an incidence of 1.5 per 1000 cases. Urinary ascites is a result of undiagnosed iatrogenic bladder injury during pelvic surgeries. We report a rare case of urinary ascites following mini lap tubectomy on the eighth postoperative day. After the diagnosis was made, conservative management was done for the patient, to which she successfully responded. PMID- 22084795 TI - Surgical Treatment of Iatrogenic Rectourinary Fistula-York-Mason Technique-a Case Report. AB - Introduction. Recto-urinary fistulas resulting from trauma or surgery are a serious and debilitating complication. They represent a challenge not only because of the difficulty on choosing the best technique to solve them but also because of the risk of recurrence. Spontaneous cure is rare. Materials and Methods. We describe the case of a 61-years-old man that on the 9th postoperative day of a laparoscopic radical prostatectomy (LRP) started with fecaluria and liquid faeces. Recto-urinary fistula was confirmed at the 10th postoperative day by CT scan and contrast enema. Discussion. We chose the York-Mason technique, because it is simple to perform, effective and has minimal morbidity. This is a posterior, transrectal, and transsphincteric approach, carried out on healthy tissues without previous scarring phenomena. Results. The postoperative period progressed without complications, and the patient discharged on the 4th day. The closure of the fistula was confirmed radiologically by retrograde cystography after 4 weeks allowing the removal of drainage catheter. The reconstruction of intestinal transit was carried out 2 months later. Conclusion. The York-Mason technique, a transrectal and transsphincteric approach with minimal morbidity, proved to be effective on the resolution of the recto-urinary fistula, a rare complication of the radical prostatectomy. PMID- 22084796 TI - Novel vitamin d analogs for prostate cancer therapy. AB - Prostate cells contain specific receptors for 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)(2)D] or calcitriol, the active form of vitamin D. 1alpha,25(OH)(2)D is known to inhibit the proliferation and invasiveness of prostate cancer cells. These findings support the use of 1alpha,25(OH)(2)D for prostate cancer therapy. However, 1alpha,25(OH)(2)D can cause hypercalcemia, analogs of 1alpha,25(OH)(2)D that are less calcemic but exhibit potent antiproliferative activity would be attractive as therapeutic agents. To accomplish these goals, different strategies, based on metabolism, molecular mechanism of actions, and structural modeling, have been taken to modify the structure of vitamin D molecule with the aims to improve the efficacy and decrease the toxicity of vitamin D to treat different diseases. During the past four decades, over 3,000 analogs have been synthesized. In this paper, we discuss the development and the biological analysis of a unique class of vitamin D analogs with a substitution at the carbon 2 of 19-nor-1alpha,25(OH)(2)D(3) molecule for potential application to the prevention and treatment of prostate cancer as well as other cancers. PMID- 22084797 TI - Intravesical tension-free vaginal tape removal: is there a single solution? AB - Stress urinary incontinence (SUI) affects 10-20% of women in the general population. Surgery for stress incontinence has been performed on women for over a century, but with the advent of new urogynaecological sling procedures for its management, urological surgeons are having to deal with an increasing number of patients presenting with associated complications. With no clarity on the full range of possible complications or certain consensus on their optimal management, the ideal treatment remains a decision for the individual surgeon. In view of this, we felt it of common interest to review the literature for the history of sling procedures, present commonly arising complications, and seek to answer the question in the title. PMID- 22084798 TI - Assessment of the effects of zoledronic Acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastatasis. AB - Purpose. Assessment of effects of zoledronic acid therapy on bone metabolic indicators in hormone-resistant prostate cancer patients with bone metastasis. Material and Methods. Hormone-resistant prostate cancer patients who were identified to have metastases in their bone scintigraphy were taken to trial group. Before administration of zoledronic acid, routine tests for serum calcium, total alkalen phosphates were studied. Sample sera for bone metabolic indicators BALP, PINP, and ICTP were collected. Bone pain was assessed via visual analogue scale and performance via Karnofsky performance scale. Four mg zoledronic acid was administered intravenously once a month. Results. When serum levels of bone forming indicators PINP; BALP were compared before and after therapy, there were insignificant decreases (P = .33, P = .21, resp.). Serum levels of bone destruction indicator ICTP was compared, and there was a significant decrease after zoledronic acid therapy (P = .04). When performances of the patients were compared during therapy period, performances decreased significantly due to progress of illness (P = .01). All patients had ostalgia caused by bone metastases at various degrees. Significant decrease in pain scores was observed (P < .01). Conclusion. Zoledronic acid therapy decreased bone destruction and was effective in palliation of pain in patient with bone metastasis. Using bone metabolic indicators during followup of zoledronic acid therapy might be useful. PMID- 22084799 TI - Penile reconstruction for a case of genital lymphoedema secondary to proteus syndrome. AB - To our knowledge penile lymphoedema secondary to Proteus syndrome has not previously been reported. Hence we report a case of a 16-year-old male who was referred with features of right hemi-hypertrophy and severe lymphoedema affecting his scrotum and penis. He had previously undergone scrotal reduction surgery at the age of 13, but had since developed worsening penile oedema. His main concern was that of cosmetic appearance prior to sexual debut, and he also complained of erectile dysfunction. An MRI confirmed gross oedema of the penile skin, but normal underlying cavernosal structure, and no other anatomical abnormality. Under general anaesthesia, the entire diseased penile skin was excised. Two full thickness skin grafts were harvested from the axillae, and grafted onto the dorsal and ventral penile shaft respectively. A compressive dressing and urinary catheter was applied for 7 days. Follow-up at 4 months confirmed complete graft take with minimal scarring, and the patient was very satisfied with the cosmetic outcome. He had also noticed a recovery in erectile activity, and feels psychologically and physically more prepared for sexual relations. PMID- 22084800 TI - Downstaging of TURBT-Based Muscle-Invasive Bladder Cancer by Radical Cystectomy Predicts Better Survival. AB - Differences between clinical (cT) and pathological tumor (pT) stage occur often after radical cystectomy (RC) for muscle-invasive bladder cancer. In order to evaluate the impact of downstaging on recurrence and survival, we selected patients from a large, contemporary, population-based series of 1,409 patients with MIBC. We included all patients who underwent RC (N=643) and excluded patients who received (neo)adjuvant therapy, those with known metastasis at time of diagnosis, and those with nonurothelial cell tumors. Disease outcomes were defined as recurrence-free survival (RFS) and relative survival (RS), as a good approximation of bladder cancer-specific survival. After applying the exclusion criteria, 375 patients were eligible for analysis. Tumor downstaging was found to be common after RC; in 99 patients (26.4%), tumor downstaging to non-muscle invasive stages at RC occurred. Hydronephrosis at baseline and positive lymph nodes at RC occurred significantly less often in these patients. In 62 patients, no tumor was left in the cystectomy specimen. pT stage was pT1 in 20 patients and pTis in 17 patients. Patients with tumor downstaging have about a 30% higher RFS and RS compared to those without. Consequently, tumor downstaging is a favorable marker for prognosis after RC. PMID- 22084801 TI - Metastatic bladder cancer: a review of current management. AB - Bladder cancer continues to result in substantial morbidity and mortality for affected individuals. Advances in the management of metastatic bladder cancer have been limited. Chemotherapy with platinum-based regimes remains the mainstay of first-line treatment. Studies investigating alternative regimes have offered no survival advantage. Targeted therapies may offer benefit either as single agent or in combination with chemotherapy. Symptoms due to metastatic bladder cancer impact patients' quality of life, and therefore holistic management is vital. Such management includes radiotherapy, bisphosphonates, and the involvement of specialist palliative care services. This review will discuss the current management for metastatic bladder cancer, future potential treatment modalities, and the evidence to support the management strategies. PMID- 22084802 TI - Unique presentation of intra-abdominal testis: small bowel obstruction. AB - We describe here a two-year-old male who required urgent laparotomy to relieve a strangulated small bowel caused by internal herniation around an intra-abdominal testis. This clinical presentation has not been reported previously. PMID- 22084803 TI - Extraluminal colonic carcinoma invading into kidney: a case report and review of the literature. AB - Renal metastasis from primary colon cancer is very rare, comprising less than 3% of secondary renal neoplasms. There are just 11 cases reported in the medical literature of colonic adenocarcinoma metastatic to the kidney. Of these cases, none occurred via direct invasion. We report a unique case of a 51-year-old female with extraluminal colonic adenocarcinoma which directly invaded into the kidney. Additionally, we investigate the causal relationship between the site of invasion and a previous stab injury by reviewing the role of the peritoneum and Gerota's fascia in preventing the spread of metastatic cancer into the perirenal space. Due to the rarity of this event, we present this case including a review of the existing literature relative to the diagnosis and treatment. PMID- 22084804 TI - Mule bite to the male genitalia with complete penile and anterior urethra amputation: unusual case and review of the literature. AB - Animal bite is rare with few cases reported in the literature. The morbidity of animal bites is directly related to the severity of the initial wound. Most victims are boys, and dog bites are the most common injury. Infectious complications are unusual, since treatment is sought early (Wein 2007). Thus, urologists are not usually familiar with management and principles for treating this condition. The authors report the case of a 38-year-old male with a severe mule bite injury to the genitalia causing complete penile and anterior urethra amputation and scrotal wound with no involvement of its contents. To our knowledge, no such case had ever been reported in the medical literature. This kind of emergencies is challenging for urologists. PMID- 22084805 TI - Small cell carcinoma of the renal pelvis: a case report and review of the literature. AB - Extrapulmonary small cell carcinoma occurs in nearly all organs except the central nervous system and the liver. We are presenting a case of renal small cell carcinoma (SCC) with two unique characters. A 75-year-old patient was evaluated for back pain with no other complaints. Magnetic Resonance (MR) imaging of the abdomen revealed homogeneous tumor in the left renal pelvis extending beyond the kidney. Metastatic workup was negative. A left nephroureterectomy was performed. Histopathology and immunohistochemistry revealed a small cell carcinoma of the renal pelvis. The patient declined adjuvant therapy and died 2 months after surgery due to unrelated causes. After comprehensive worldwide literature search, we found 13 cases of SCC of the renal pelvis, including the current case. The mean age was 61.6 years (37-83), with a M : F ratio of 1 : 1.8. The average duration of symptoms was 71.4 days (21-168). Gross hematuria was the most common symptom (69.2%) followed by pain (61.5%). Adjuvant chemotherapy was provided to 4 patients (30.7%), and neoadjuvant to 1 patient. The median survival of patients who did and did not receive chemotherapy was 5.5 months (3-8) and 6 months (2-31), respectively, P < .50. In conclusion, renal SCC (both parenchymal and pelvic SCC) is a rapidly fatal disease with a median survival of <=8 months. PMID- 22084806 TI - Urachal sinus presenting with abscess formation. AB - Urachal affections are rare. Their variable ways of presentation may represent a diagnostic challenge. Urachal sinuses are a rare type of these abnormalities. They are usually incidental findings and remain asymptomatic unless a complication (most commonly the infection) occurs. Infection of the urachal sinus would clinically present as purulent umbilical discharge, abdominal pain, and periumbilical mass. We report herein a case of infected urachal sinus in male adult. The diagnosis was suspected clinically and confirmed with ultrasonography and computed tomography scan. A preoperative cysto-fibroscopy showed normal aspect of the bladder and excluded sinus communication. An initial broad spectrum antibiotic therapy followed by complete excision of the sinus and fibrous tract without cuff of bladder has been therefore performed. The postoperative course was uneventful. No recurrence was observed after 18 months of followup. Histological examination did not reveal any sign of malignancy. PMID- 22084807 TI - Spinal versus General Anaesthesia in Postoperative Pain Management during Transurethral Procedures. AB - We compared the analgesic efficacy of spinal and general anaesthesia following transurethral procedures. 97 and 47 patients underwent transurethral bladder tumour resection (TUR-B) and transurethral prostatectomy (TUR-P), respectively. Postoperative pain was recorded using an 11-point visual analogue scale (VAS). VAS score was greatest at discharge from recovery room for general anaesthesia (P = 0.027). The pattern changed significantly at 8 h and 12 h for general anaesthesia's efficacy (P = 0.017 and P = 0.007, resp.). A higher VAS score was observed in pT2 patients. Patients with resected tumour volume >10 cm(3) exhibited a VAS score >3 at 8 h and 24 h (P = 0.050, P = 0.036, resp.). Multifocality of bladder tumours induced more pain overall. It seems that spinal anaesthesia is more effective during the first 2 postoperative hours, while general prevails at later stages and at larger traumatic surfaces. Finally, we incidentally found that tumour stage plays a significant role in postoperative pain, a point that requires further verification. PMID- 22084808 TI - The recent progress in quantitative medical image analysis for computer aided diagnosis systems. AB - Computer-aided diagnosis (CAD) has become one of the major research subjects in medical imaging and diagnostic radiology. Many different CAD schemes are being developed for use in the detection and/or characterization of various lesions found through various types of medical imaging. These imaging technologies employ conventional projection radiography, computed tomography, magnetic resonance imaging, ultrasonography, etc. In order to achieve a high performance level for a computerized diagnosis, it is important to employ effective image analysis techniques in the major steps of a CAD scheme. The main objective of this review is to attempt to introduce the diverse methods used for quantitative image analysis, and to provide a guide for clinicians. PMID- 22084809 TI - Recognizing Temporal Information in Korean Clinical Narratives through Text Normalization. AB - OBJECTIVES: Acquiring temporal information is important because knowledge in clinical narratives is time-sensitive. In this paper, we describe an approach that can be used to extract the temporal information found in Korean clinical narrative texts. METHODS: We developed a two-stage system, which employs an exhaustive text analysis phase and a temporal expression recognition phase. Since our target document may include tokens that are made up of both Korean and English text joined together, the minimal semantic units are analyzed and then separated from the concatenated phrases and linguistic derivations within a token using a corpus-based approach to decompose complex tokens. A finite state machine is then used on the minimal semantic units in order to find phrases that possess time-related information. RESULTS: In the experiment, the temporal expressions within Korean clinical narratives were extracted using our system. The system performance was evaluated through the use of 100 discharge summaries from Seoul National University Hospital containing a total of 805 temporal expressions. Our system scored a phrase-level precision and recall of 0.895 and 0.919, respectively. CONCLUSIONS: Finding information in Korean clinical narrative is challenging task, since the text is written in both Korean and English and frequently omits syntactic elements and word spacing, which makes it extremely noisy. This study presents an effective method that can be used to aquire the temporal information found in Korean clinical documents. PMID- 22084810 TI - Exploring the Possibility of Information Sharing between the Medical and Nursing Domains by Mapping Medical Records to SNOMED CT and ICNP. AB - OBJECTIVES: The purpose of this study is to explore possibility of information sharing between the medical and nursing domains. METHODS: Narrative medical records of 281 hospitalization days of 36 gastrectomy patients were decomposed into single-meaning statements. These single-meaning statements were combined into unique statements by removing semantically redundant statements. Concepts from the statements describing patients' problem and medical procedures were mapped to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) and International Classification for Nursing Practice (ICNP) concepts. RESULTS: A total 4,717 single-meaning statements were collected and these single-meaning statements were combined into 858 unique statements. Out of 677 unique statements describing patients' problems and medical procedures, about 85.5% statements were fully mapped to SNOMED CT. The remaining statements were partially mapped. In the mapping to the ICNP concepts, 17.4% of unique statements were fully mapped, 62.8% were partially mapped, and 19.8% were not mapped. About 32.3% of 705 concepts extracted from the statements were mapped to both SNOMED CT and ICNP concepts. CONCLUSIONS: These mapping results suggest that physicians' narrative medical records can be structured and can be used for electronic medical record system, and also it is possible for medicine and nursing to share patient care information. PMID- 22084811 TI - A SWOT Analysis of the Various Backup Scenarios Used in Electronic Medical Record Systems. AB - OBJECTIVES: Electronic medical records (EMRs) are increasingly being used by health care services. Currently, if an EMR shutdown occurs, even for a moment, patient safety and care can be seriously impacted. Our goal was to determine the methodology needed to develop an effective and reliable EMR backup system. METHODS: Our "independent backup system by medical organizations" paradigm implies that individual medical organizations develop their own EMR backup systems within their organizations. A "personal independent backup system" is defined as an individual privately managing his/her own medical records, whereas in a "central backup system by the government" the government controls all the data. A "central backup system by private enterprises" implies that individual companies retain control over their own data. A "cooperative backup system among medical organizations" refers to a networked system established through mutual agreement. The "backup system based on mutual trust between an individual and an organization" means that the medical information backup system at the organizational level is established through mutual trust. RESULTS: Through the use of SWOT analysis it can be shown that cooperative backup among medical organizations is possible to be established through a network composed of various medical agencies and that it can be managed systematically. An owner of medical information only grants data access to the specific person who gave the authorization for backup based on the mutual trust between an individual and an organization. CONCLUSIONS: By employing SWOT analysis, we concluded that a linkage among medical organizations or between an individual and an organization can provide an efficient backup system. PMID- 22084812 TI - The adoption of electronic medical records and decision support systems in Korea. AB - OBJECTIVES: To examine the current status of hospital information systems (HIS), analyze the effects of Electronic Medical Records (EMR) and Clinical Decision Support Systems (CDSS) have upon hospital performance, and examine how management issues change over time according to various growth stages. METHODS: Data taken from the 2010 survey on the HIS status and management issues for 44 tertiary hospitals and 2009 survey on hospital performance appraisal were used. A chi square test was used to analyze the association between the EMR and CDSS characteristics. A t-test was used to analyze the effects of EMR and CDSS on hospital performance. RESULTS: Hospital size and top management support were significantly associated with the adoption of EMR. Unlike the EMR results, however, only the standardization characteristic was significantly associated with CDSS adoption. Both EMR and CDSS were associated with the improvement of hospital performance. The EMR adoption rates and outsourcing consistently increased as the growth stage increased. The CDSS, Knowledge Management System, standardization, and user training adoption rates for Stage 3 hospitals were higher than those found for Stage 2 hospitals. CONCLUSIONS: Both EMR and CDSS influenced the improvement of hospital performance. As hospitals advanced to Stage 3, i.e. have more experience with information systems, they adopted EMRs and realized the importance of each management issue. PMID- 22084813 TI - Japanese EMRs and IT in Medicine: Expansion, Integration, and Reuse of Data. AB - OBJECTIVES: The prevalence of electronic medical record in Japan varies according to the size of the hospital which is 62.5% in major hospitals, 21.7% in medium, 9.1% in small size hospitals, and 16.5% in clinics. The complete paperless system is very limited, though some major hospitals are aiming at this system. Several regional network systems which connect different platforms of EMRs, have been developing in many districts, while the final picture of a regional network has not been clearly proposed. To develop a whole electronic health record or personal health records system from the regional network data, we have several obstacles to overcome such as standardization, a privacy act, unique national health number. METHODS: Some experimental trials have just been started. The reuse of the accumulated data has also just been initiated. We exploited text mining systems (term frequency-inverse document frequency method) to find similar cases and auto-audit Japanese diagnosis related group (DRG) coding by using discharge summaries. RESULTS: The same or even a more extreme phenomenon of huge data accumulation is occurring in genetic research and confluence of multi disciplines of informatics is the next step, which has an enormous accumulation of data and discoveries of the relations beyond the dimension of each informatics. CONCLUSIONS: We need another approach to science apart from the conventional method, and data-driven approach with data mining techniques must be brought in for each field. Informaticians have new important roles as coordinators to link up numerous phenomena over dimensions. PMID- 22084814 TI - Leveraging devices, data and discovery for smarter healthcare in Japan. AB - OBJECTIVES: Over the past decade, hospitals and clinics have gradually adopted hospital information systems, including provider order entries and electronic health records. Although these systems have helped to improve patient safety and efficiency of healthcare providers, not all healthcare providers and patients are satisfied with the current situation. Healthcare should be smarter. Thus, there is a need for state-of-the-art medical and healthcare devices that can handle massive amounts of data with the help of sophisticated information processing and discovery technologies. METHODS: This article compares hospital information systems with the information systems of other social infrastructures. It also explores the possibilities of smarter healthcare, including personal health devices and personal health records with interoperability. RESULTS: The main traits of the iEHR at Teikyo University Hospital in Tokyo include IT governance, unification, and workflow efficiency. CONCLUSIONS: Smarter healthcare can be achieved by leveraging the full capabilities of devices, data, and sophisticated algorithms. PMID- 22084815 TI - eHealth in Queensland: Progressing towards a Patient Centric, Networked Model of Care. AB - OBJECTIVES: Factors such as an ageing and rapidly growing population, an increase in chronic disease rates and a global shortage of health professionals place increased pressure on Australian health departments to deliver more with less. To address the challenge faced by clinicians and support staff, the Queensland Department of Health established an eHealth strategy in 2006 with a vision to deliver a patient centric, networked model of care. METHODS: Queensland Health's eHealth program is a complex program which brings together the outputs and products of numerous projects to provide new clinical capabilities across the state. To ensure the potential benefits of the Queensland Government investment are realised, the eHealth program is implementing comprehensive benefits management to plan for key outcomes and benefits, support projects to deliver those benefits and ensure that they are delivered through ongoing measurement. RESULTS: The first stage of the eHealth program is already delivering benefits across the health department with a number of projects currently live in numerous sites across Queensland. CONCLUSIONS: By adopting an evidence based benefits management approach, Queensland Health's eHealth program is able to demonstrate the achievement of these benefits with tangible evidence that will create momentum for change in the short term, provide the evidence for future funding applications in the medium term, and build an understanding of the economic impacts of eHealth in the long term. PMID- 22084816 TI - Mild chemo-selective hydration of terminal alkynes catalysed by AgSbF6. AB - The chemo-selective hydration of a wide range of non-activated terminal alkynes catalysed by AgSbF(6) under mild conditions is reported. PMID- 22084817 TI - Encapsulation, release and applications of LbL polyelectrolyte multilayer capsules. AB - Ever since their invention in 1998, polyelectrolyte multilayer micro- and nano capsules have impacted various areas of biology, chemistry and physics. Here we highlight progress achieved since the millennium in the areas of encapsulation in and release from microcapsules, describe various structures including multicompartment and anisotropic constructs, and provide examples of several applications in biology. We also describe application areas such as drug delivery, intracellular trafficking, enzyme-catalyzed reactions, mechano-biology which benefited from recent developments in the area of polyelectrolyte multilayer capsules. PMID- 22084818 TI - Using functional-structural plant models to study, understand and integrate plant development and ecophysiology. AB - Functional-structural plant models (FSPMs) explore and integrate relationships between a plant's structure and processes that underlie its growth and development. In recent years, the range of topics being addressed by scientists interested in functional-structural plant modelling has expanded greatly. FSPM techniques are now being used to dynamically simulate growth and development occurring at the microscopic scale involving cell division in plant meristems to the macroscopic scales of whole plants and plant communities. The plant types studied also cover a broad spectrum from algae to trees. FSPM is highly interdisciplinary and involves scientists with backgrounds in plant physiology, plant anatomy, plant morphology, mathematics, computer science, cellular biology, ecology and agronomy. This special issue of Annals of Botany features selected papers that provide examples of comprehensive functional-structural models, models of key processes such as partitioning of resources, software for modelling plants and plant environments, data acquisition and processing techniques and applications of functional-structural plant models for agronomic purposes. PMID- 22084819 TI - The pendulum of anti-industry sentiment. PMID- 22084821 TI - [Not Available]. PMID- 22084820 TI - Retraction: Erratum to "The effectiveness of Korean number naming on insight into numbers in Dutch students with mild intellectual disabilities" [Res. Dev. Disabil. 32 (5) (2011) 1822-1828]. PMID- 22084822 TI - New Zealand's bold strategy for reducing health disparities. PMID- 22084823 TI - Keeping focused. PMID- 22084824 TI - Care of the endurance athlete: promotion, perception, performance and professionalism. PMID- 22084826 TI - HIV-related conspiracy beliefs and its relationships with HIV testing and unprotected sex among men who have sex with men in Tshwane (Pretoria), South Africa. AB - The objective of this study was to determine extent of HIV conspiracy belief endorsement among men who have sex with men (MSM) in Pretoria, and assess whether endorsement of HIV conspiracy beliefs are associated with inconsistent condom use and never testing for HIV. A cross-sectional survey using respondent-driven sampling was conducted between February and August 2009. A high proportion of respondents endorsed HIV conspiracy beliefs. MSM commonly endorsed beliefs related to AIDS information being held back from the general public (51.0%), HIV being a man-made virus (25.5%), and people being used as guinea pigs in HIV research and with HIV treatments (approximately 20%). Bisexually- or heterosexually-identified MSM were significantly more likely to endorse conspiracy beliefs compared to homosexually-identified MSM (38.5% vs. 14.7%). Endorsing conspiracy beliefs was not associated with unprotected anal intercourse; however, it was significantly associated with not having been HIV tested (AOR: 2.4; 95% CI: 1.1-5.7). Endorsing beliefs in HIV conspiracies reflects a mistrust in government institutions and systems which could be an impediment to seeking HIV-related services, including HIV counseling and testing. PMID- 22084827 TI - Remarkable enhancement in thermoelectric performance of BiCuSeO by Cu deficiencies. AB - A significant enhancement of thermoelectric performance in layered oxyselenides BiCuSeO was achieved. The electrical conductivity and Seebeck coefficient of BiCu(1-x)SeO (x = 0-0.1) indicate that the carriers were introduced in the (Cu(2)Se(2))(2-) layer by Cu deficiencies. The maximum of electrical conductivity is 3 * 10(3) S m(-1) for Bicu(0.975)Seo at 650 degrees C, much larger than 470 S m(-1) for pristine BiCuSeO. Featured with very low thermal conductivity (~0.5 W m(-1) K(-1)) and a large Seebeck coefficient (+273 MUV K(-1)), ZT at 650 degrees C is significantly increased from 0.50 for pristine BiCuSeO to 0.81 for BiCu(0.975)SeO by introducing Cu deficiencies, which makes it a promising candidate for medium temperature thermoelectric applications. PMID- 22084828 TI - Exploring the surface sensitivity of TOF-secondary ion mass spectrometry by measuring the implantation and sampling depths of Bi(n) and C60 ions in organic films. AB - The surface sensitivity of Bi(n)(q+) (n = 1, 3, 5, q = 1, 2) and C(60)(q+) (q = 1, 2) primary ions in static time-of-flight secondary ion mass spectrometry (TOF SIMS) experiments were investigated for molecular trehalose and polymeric tetraglyme organic films. Parameters related to surface sensitivity (impact crater depth, implantation depth, and molecular escape depths) were measured. Under static TOF-SIMS conditions (primary ion doses of 1 * 10(12) ions/cm(2)), the 25 keV Bi(1)(+) primary ions were the most surface sensitive with a molecular escape depth of 1.8 nm for protein films with tetraglyme overlayers, but they had the deepest implantation depth (~18 and 26 nm in trehalose and tetraglyme films, respectively). The 20 keV C(60)(+2) primary ions were the second most surface sensitive with a slightly larger molecular escape depth of 2.3 nm. The most important factor that determined the surface sensitivity of the primary ion was its impact crater depth or the amount of surface erosion. The most surface sensitive primary ions, Bi(1)(+) and C(60)(+2), created impact craters with depths of 0.3 and 1.0 nm, respectively, in tetraglyme films. In contrast, Bi(5)(+2) primary ions created impact craters with a depth of 1.8 nm in tetraglyme films and were the least surface sensitive with a molecular escape depth of 4.7 nm. PMID- 22084829 TI - Proteomic characterization of specific minor proteins in the human milk casein fraction. AB - Human milk contains many bioactive proteins that are likely to support the early development of the newborn. The aim of this study was to identify whether there are specific minor proteins associated with the human milk casein micelle prepared by the acid precipitation method. Protein identification was performed by liquid chromatography tandem mass spectrometry analysis. Eighty-two proteins were identified in the casein micelle, 18 of which are not present in their whey compartment. Thirty-two of these proteins specifically associated with the casein micelle have not previously been identified in human milk or colostrum. Proteins involved in immune function comprised the major part (28%) of total proteins, and another significant part is involved in metabolism/energy production (22%). Most of the proteins were of extracellular or cytoplasmic origin (accounting for 50 and 29%, respectively). This study indicates that various soluble proteins should be considered as part of the casein compartment, prepared by the acid precipitation method. The data provide new insight not only into the proteomic profile of the human milk casein micelle and its physiological significance, but also into the proper proportion of casein and casein-associated proteins to use in infant formula. PMID- 22084830 TI - 2D "soap"-assembly of nanoparticles via colloid-induced condensation of mixed Langmuir monolayers of fatty surfactants. AB - We describe a new type of colloidal 2D gels formed in mixed Langmuir monolayers of stearic acid and octadecylamine on a surface of gold hydrosol. The adsorption of gold nanoparticles on the mixed monolayer led to an increase of interactions between oppositely charged surfactants giving a "soap" of mixed fatty salt. The observed effect is equivalent to a virtual "cooling" of floating monolayer, which undergoes rapid condensation on a surface of aqueous colloid. The consequent shrinking and rearrangement of the monolayer resulted in aggregation of nanoparticles into colloidal 2D "soap"-gels, which represented arrested colloidal phases within nonadsorbing organic medium. When sequentially deposited onto solids by Langmuir-Blodgett technique, the 2D "soap"-gels separated into organic and colloidal phases and gave dendrite-like bilateral organic crystallites coated with gold nanoparticles. The reported colloidal "soap"-assembly can offer a new opportunity to design 2D colloidal systems of widely variable chemistry and structures. PMID- 22084831 TI - Protective and restorative effects of a Commiphora mukul gum resin and triheptanoin preparation on the CCL-110 skin fibroblast cell line. AB - Coenzyme Q10 (CoQ10) is a major ingredient in skin care products because of its anti-wrinkle effects, although it has some side effects especially at higher amounts. In this study, we compare the anti-wrinkle related properties of CoQ10 and a proprietary Commiphora mukul gum resin (guggul) and triheptanoin preparation (GU-TC7). GU-TC7 is prepared with a supercritical CO2-co-solvent extraction with ethanol, standardized to 2% guggulsterones and triheptanoin, a triglyceride composed of three 7-carbon fatty acids. Treatment of CCL-110 skin fibroblasts with GU-TC7 demonstrates a mild proliferative effect compared to CoQ10 and increased type I collagen synthesis. Additionally, GU-TC7 inhibited matrix metalloproteinase-1 (MMP-1) expression in a dose-dependent manner at 20 100 MUg mL-1 and inhibited human elastase expression by more than 50% as compared to no elastase inhibition with CoQ10 treatment. These results suggest that GU-TC7 possesses properties that are applicable to the treatment of wrinkles and may be considered for its further evaluation in skin care products. PMID- 22084832 TI - Morphological examinations of oxidatively stressed pork muscle and myofibrils upon salt marination and cooking to elucidate the water-binding potential. AB - Pork longissimus muscle samples were subjected to the following three marination conditions: (A) oxidation (40 min) in hydroxyl radical-generating solutions (HRGS; 10 MUM FeCl(3)/100 MUM ascorbate with 5 or 20 mM H(2)O(2), pH 6.2) containing 0.1 M NaCl and then marination (40 min) in 0.6 M NaCl with 15 mM pyrophosphate (PP); (B) simultaneous oxidation/marination (40 min) in HRGS containing 0.6 M NaCl and 15 mM PP; or (C) the same as condition B except that PP was omitted. Protein oxidation, measured by the carbonyl and tryptophan fluorescence changes, enhanced hydration but increased cooking loss of meat. Light microscopy revealed a dense muscle structure characterized by swollen fibers and reduced intercellular spacing in intermediately oxidized muscle samples marinated with 0.6 M NaCl and 15 mM PP. However, oxidized fibers were more susceptible to transverse shrinkage upon cooking than nonoxidized fibers, which was supported by the dynamic ultrastructural changes in myofibrils observed using phase contrast microscopy. These findings provide a further understanding of the complex impact of oxidation on meat hydration and water-binding. PMID- 22084833 TI - A new quantitative automatic method for the measurement of non-rapid eye movement sleep electroencephalographic amplitude variability. AB - The aim of this study was to arrange an automatic quantitative measure of the electroencephalographic (EEG) signal amplitude variability during non-rapid eye movement (NREM) sleep, correlated with the visually extracted cyclic alternating pattern (CAP) parameters. Ninety-eight polysomnographic EEG recordings of normal controls were used. A new algorithm based on the analysis of the EEG amplitude variability during NREM sleep was designed and applied to all recordings, which were also scored visually for CAP. All measurements obtained with the new algorithm correlated positively with corresponding CAP parameters. In particular, total CAP time correlated with total NREM variability time (r = 0.596; P < 1E 07), light sleep CAP time with light sleep variability time (r = 0.597; P < 1E 07) and slow wave sleep CAP time with slow wave sleep variability time (r = 0.809; P < 1E-07). Only the duration of CAP A phases showed a low correlation with the duration of variability events. Finally, the age-related modifications of CAP time and of NREM variability time were found to be very similar. The new method for the automatic analysis of NREM sleep amplitude variability presented here correlates significantly with visual CAP parameters; its application requires a minimum work time, compared to CAP analysis, and might be used in large studies involving numerous recordings in which NREM sleep EEG amplitude variability needs to be assessed. PMID- 22084834 TI - A population-based longitudinal community study of major depression and migraine. AB - OBJECTIVE: To examine whether major depressive episodes (MDEs) are associated with an increased risk of migraine in the general population and to examine whether migraine is associated with an increase risk of MDE. BACKGROUND: Population-based cross-sectional studies have consistently reported an association between migraine and depression. However, longitudinal studies about this potentially bidirectional association are inconsistent. METHODS: This retrospective cohort study used 12 years of follow-up data from the Canadian National Population Health Survey (15,254 respondents, age >12). Stratified analysis, logistic regression, and proportional hazard modeling were used to quantify the effect of migraine on subsequent MDE status and vice versa. RESULTS: After adjusting for sex, age, and other chronic health conditions, respondents with migraine were 60% more likely (HR 1.6, 95% confidence interval 1.3-1.9) to develop MDE compared with those without migraine. Similarly adjusting for sex and age, respondents with MDE were 40% more likely (HR 1.4, 95% confidence interval 1.0-1.9) to develop migraine compared with those without MDE. However, the latter association disappeared after adjustment for stress and childhood trauma. CONCLUSIONS: The current study provides substantial evidence that migraine is associated with the later development of MDEs, but does not provide strong causal evidence of an association in the other direction. Environmental factors such as childhood trauma and stress may shape the expression of this bidirectional relationship; however, the precise underlying mechanisms are not yet known. PMID- 22084835 TI - Asymmetric hydrogenation on chirally modified Pt: origin of hydrogen in the N-H-O interaction between cinchonidine and ketone. AB - An understanding of the chiral site-substrate interaction is a necessary prerequisite for the rational design and development of efficient heterogeneous asymmetric catalysts. For the enantioselective hydrogenation of alpha-ketoesters on cinchona-modified platinum, it has earlier been proposed that the crucial interaction is an N-H-O type hydrogen bonding between the quinuclidine N atom of cinchonidine and the alpha-carbonyl O atom of the substrate. The involved hydrogen atom has been proposed to originate either from protonation (in protic solvent) or from dissociatively adsorbed hydrogen (in aprotic solvent), but experimental evidence for the latter was lacking so far. In this study, in situ attenuated total reflection infrared spectroscopy combined with modulation excitation spectroscopy and phase sensitive detection provides clear evidence that in aprotic media, hydrogen dissociated on Pt is involved in the N-H-O interaction between the chiral modifier, cinchonidine, and the ketone. In the absence of Pt (pure alumina support), no such interaction occurs, indicating the crucial role of dissociated hydrogen in the formation of the diastereomeric transition complex. PMID- 22084836 TI - Fetal growth and gestational hypertension in women classified as gestational diabetes mellitus defined by the new consensus criteria only. PMID- 22084837 TI - Functional identification of a novel F-box/FBA gene in tomato. AB - In plants and animals, the SCF-type ubiquitin protein ligases play an important role in many different physiological processes by regulating protein stability such as S-RNase-based self-compatibility, flower development, hormone responses and meiosis. This study identified an SlFbf gene in tomato that encodes 381 amino acid residues containing a typical F-box motif and an FBA_1 motif associated proteasome pathway; the transcripts of SlFbf was detected in all the tissues (root, stem, leaf, sepal, petal, stamen, pistil, green fruit, breaker fruit and red fruit), with the highest in stamen specifically during flowering stage; SlFbf responded to gibberellins, abscisic acid and light. Suppressed SlFbf leads to bigger pollen and less seeds showing that SlFbf might have an effect on fertilization through regulating stamen development. These findings provide more information about the functions of Fbf gene family. PMID- 22084838 TI - Homochiral metal-organic frameworks for asymmetric heterogeneous catalysis. PMID- 22084839 TI - A donor-supply electrode (DSE) for colloidal quantum dot photovoltaics. AB - The highest-performing colloidal quantum dot (CQD) photovoltaics (PV) reported to date have relied on high-temperature (>500 degrees C) annealing of electron accepting TiO2. Room-temperature processing reduces energy payback time and manufacturing cost, enables flexible substrates, and permits tandem solar cells that integrate a small-bandgap back cell atop a low-thermal-budget larger-bandgap front cell. Here we report an electrode strategy that enables a depleted heterojunction CQD PV device to be fabricated entirely at room temperature. We find that simply replacing the high-temperature-processed TiO2 with a sputtered version of the same material leads to poor performance due to the low mobility of the sputtered oxide. We develop instead a two-layer donor-supply electrode (DSE) in which a highly doped, shallow work function layer supplies a high density of free electrons to an ultrathin TiO2 layer via charge-transfer doping. Using the DSE we build all-room-temperature-processed small-bandgap (1 eV) colloidal quantum dot solar cells having 4% solar power conversion efficiency and high fill factor. These 1 eV bandgap cells are suitable for use as the back junction in tandem solar cells. The DSE concept, combined with control over TiO2 stoichiometry in sputtering, provides a much-needed tunable electrode to pair with quantum-size-effect CQD films. PMID- 22084840 TI - Variations in microbicide gel acceptability among young women in the USA and Puerto Rico. AB - In a multi-site study of vaginal microbicide acceptability conducted with sexually active young women, quantitative assessments revealed significant differences in acceptability by site. Participants in Puerto Rico rated the gel more favourably than mainland US participants in terms of liking the gel and likelihood of future use. To explain these differences, we examined responses to qualitative behavioural assessments. Young women in mainland USA associated gel leakage with uncomfortable sensations experienced during menstruation, while young women in Puerto Rico had positive associations of gel use with douching. These negative or positive associations affected assessments of the gel's physical qualities. In addition, young women's perceptions of primary partners' support for microbicide use influenced sexual satisfaction with the gel and, ultimately, product acceptability. Finally, geographic HIV-risk context contributed to heightened HIV-risk perception, which influenced likelihood of future microbicide use, even for women in stated monogamous relationships. Future microbicide acceptability studies should take into account potential differences in acceptability by site such as HIV-risk perception based on local HIV prevalence, popularity of vaginal hygiene products in a specific area and male attitudes in different cultures concerning women's use of HIV protection strategies. PMID- 22084841 TI - Type 2 diabetes, cardiovascular disease and the utilisation of primary care in urban and regional settings. AB - INTRODUCTION: There are marked inequities in access to and use of different primary care providers - including GPs, practice nurses, allied health services and complementary and alternative medicine (CAM) providers among populations residing in different geographical areas of Australia. Little research has focused on patterns of primary care health service utilisation according to locality in relation to the management of serious chronic illness, with even less on the use of CAM. In this article geographic similarities and differences in primary care service usage are examined among people with cardiovascular disease and/or type 2 diabetes mellitus residing in regional and urban Victoria, Australia. METHODS: Between April and July 2010, hard-copy questionnaires were sent to a random selection of 10 000 registrants from the National Diabetes Services Scheme, 2162 were distributed via Heart Support Australia and community organisations within the state of Victoria; an online version yielded 290 valid responses. This article draws on data from the 2914 returned survey responses in which people provided their residential postal codes. From this information, geographic location was determined on the basis of the Australian Standard Geographical Classification. Data were subject to inferential analyses using PASW Statistics 18.0 (SPSS; Chicago, IL, USA). A series of contingency table analyses were conducted to evaluate the relationship between primary care service use and respondents' geographical locality. Contingency analyses and chi(2) tests were also conducted to examine the differences between rural and metropolitan frequency of GP use. RESULTS: In comparison with urban respondents, rural respondents reported greater use of allied health practitioners, district or practice nurses, and community health centres. Conversely, use of hospital outpatient services was significantly higher among metropolitan respondents. Use of GP clinics was not related significantly to respondents' locality, nor was use of inpatient hospital services or use of counselling, psychiatry or psychology services. Frequency of GP use, however, varied significantly among geographical categorisations, with urban respondents visiting their GPs more frequently. CONCLUSIONS: While GPs play an important role in chronic disease management in Australia, the rate of GP attendance remains lower among patients living in regional areas. By contrast, the level of patient engagement with nurse practitioners and allied health professionals in this study was significantly higher among rural respondents. Issues related to access appear to play an important role in determining what primary care services people use when managing their chronic conditions and their frequency of consultation. PMID- 22084842 TI - Introduction: return of research results: how should research results be handled? PMID- 22084843 TI - Return of results: towards a lexicon? AB - Currently, the return of results in the domain of biobanking constitutes an ethical and legal quagmire, whether it involves population or specific clinical research studies. In light of the fact that population biobanks are often not seen as distinct from those biobanks created for disease research, as well as the uncertainty as to what "return of results" means concretely, this lexicon attempts to demystify the terminology. The terms - results, return, clinical significance, and utility - are discussed. Through an analysis of international and national normative guidance on this issue, the authors propose a concordance of meaning and a simplified lexicon. PMID- 22084844 TI - Return of research results: general principles and international perspectives. AB - Five years ago, an article co-written by two of us (Joly and Simard) presented an emerging trend to disclose certain individual genetic results to research participants. Since then, both technologies and research practices have evolved significantly. Given this rapid evolution, our goal is to provide updated and thorough guidance on this issue. Our paper begins by identifying the ethical principles that support the return of results: justice, beneficence, and respect for persons. Then, it presents the results of an analysis of international norms on the return of results, covering both general and individual research results. It reveals existing divergence and consensus on these topics within the international community. With the goal of promoting greater harmonization, we conclude by proposing a flexible framework for the return of individual research results. PMID- 22084845 TI - Pediatric research and the return of individual research results. AB - The return of individual research results to participants raises many socio ethical issues and is even more challenging when the participant is a child. The objective of this article is to present an overview of the few ethical guidelines and relevant literature addressing the return of individual results in pediatric research. By reviewing policies and the literature, we present some overarching considerations and delineate contextual issues in order to propose a framework. PMID- 22084846 TI - Familial communication of research results: a need to know? AB - Research now provides participants greater indications of genetic risk for disease, even for conditions incidental to the research study. Given this development, should such information also be disclosed to the family of research participants? There has been some indication at the national level that genetic risk information can be disclosed to participants' families; however, limited attention has been given to returning research results to family. Thus, we have also incorporated the discussion surrounding the disclosure of genetic risk discovered in the clinic (e.g., genetic testing). A number of important questions are examined: Should genetic research results be provided to family? Are there differences between clinical and research findings that would prevent research results from being disclosed to family? Who should make the disclosure, if in fact it is done at all? We conclude by noting that the return of results is increasingly accepted as technology permits the discovery of more and more medically useful data. However, debates of whether results should be returned to participants must first be settled before moving to familial disclosure. PMID- 22084847 TI - Biobanks and the return of research results: out with the old and in with the new? AB - This article examines the complex and contemporary issue of the return of research results in biobanks. After suggesting the exclusion of some adjacent issues usually flanking the debate, this article reviews the current practices of biobanks on the disclosure of research results to participants. It then focuses more specifically on the debate in the literature before turning to a review of the typology of recent reforms being put forward. PMID- 22084848 TI - The return of results of deceased research participants. AB - The death of a research participant raises numerous ethical and legal issues regarding the return of research results to related family members. This question is particularly acute in the context of genetic research since the research results from an individual may be relevant to each of the biological relatives. This paper first investigates the ethical and legal frameworks governing the return of a deceased participant's individual research results to his or her related family members. Then, it weighs the rights and interests of both the deceased individual and related family members in an attempt to identify key ethical considerations underlying the return of such results. This analysis of international guidelines and national laws and regulations reveals that though the legal framework regarding privacy and confidentiality of clinical and research information is well established (albeit not homogenous), guidelines are generally absent in the post-mortem context. Nevertheless, a brief analysis of this issue through two ethical perspectives (principlism and consequentialism) allows us to identify six key elements to be taken into consideration when returning a deceased participant's research results. PMID- 22084849 TI - The needle in the haystack: international consortia and the return of individual research results. AB - Returning individual results to participants in research studies is gaining acceptance and policy guidance is now available for investigators to develop a plan for returning results at the local level. However, returning results discovered through the work of an international scientific research consortium presents additional ethical and procedural difficulties. No general guidance is available for international consortia that wish to consider this issue, but there are examples of internal policies that are being used by consortia such as the International Cancer Genome Consortium (ICGC) and the Type 1 Diabetes Genetics Consortium (T1DGC). This paper presents the policy stance these studies have adopted regarding returning individual research results and their reasons behind it, and gives specific examples from their policy documents and project consent materials. Finally, it suggests an oversight mechanism these and other international consortia can use to ensure that this important issue is addressed appropriately. PMID- 22084850 TI - Conflicts over control and use of medical records at the New York hospital before the standardization movement. AB - Historians of medicine generally credit the hospital standardization movement of the early 20th century with establishing the record as a sign of hospital and staff quality. The medical record's role had already been the subject of intense interest at the New York Hospital several decades before, however. In the 1880s malpractice and insurance concerns caused the administration to attempt to supervise record creation, quality, and access, over the objections of physicians. Contemporary concerns about the uses of the medical record were in play well before 1910. PMID- 22084851 TI - An ethics expertise for clinical ethics consultation. AB - The legitimacy of clinical ethics consultation is often implied to rest on the legitimacy of moral expertise. In turn, moral expertise seems subject to many serious critiques, the success of which implies that clinical ethics consultation is illegitimate. I explore a number of these critiques, and forward "ethics expertise," as distinct from "moral expertise," as a way of avoiding these critiques. I argue that "ethics expertise" succeeds in avoiding most of the critiques, captures what clinical ethics consultants might justifiably do, and expresses a subject matter which can be taught and assessed. PMID- 22084852 TI - Reforming pharmaceutical industry-physician financial relationships: lessons from the United States, France, and Japan. AB - This article compares the means that the United States, France, and Japan use to oversee pharmaceutical industry-physician financial relationships. These countries rely on professional and/or industry ethical codes, anti-kickback laws, and fair trade practice laws. They restrict kickbacks the most strictly, allow wide latitude on gifts, and generally permit drug firms to fund professional activities and associations. Consequently, to avoid legal liability, drug firms often replace kickbacks with gifts and grants. The paper concludes by proposing reforms that address problems that persist when firms replace kickbacks with gifts and grants based on the experience of the three countries. PMID- 22084853 TI - Me and my body: the relevance of the distinction for the difference between withdrawing life support and euthanasia. AB - In this paper, I discuss David Shaw's claim that the body of a terminally ill person can be conceived as a kind of life support, akin to an artificial ventilator. I claim that this position rests upon an untenable dualism between the mind and the body. Given that dualism continues to be attractive to some thinkers, I attempt to diagnose the reasons why it continues to be attractive, as well as to demonstrate its incoherence, drawing on some recent work in the philosophy of psychology. I conclude that, if my criticisms are sound, Shaw's attempt to deny the distinction between withdrawal and euthanasia fails. PMID- 22084854 TI - Communitarianism and the ethics of communicable disease: some preliminary thoughts. AB - Communicable diseases, especially those that are highly contagious, are on the rise and each of us, no matter who we are or where we live, is equally at risk of transmitting contagious diseases to others as we are of contracting such diseases from others. Because contagious diseases are as readily passed state-to-state as person-to-person, we all have a stake in every country's ability to enact effective infectious disease control policies, while policies grounded in shared values are more likely to gain widespread acceptance and thereby prove most effective. This paper suggests that principlism proved invaluable as an ethical framework for resolving hard medical cases and setting health care policy because it nicely "fits" dilemmas that arise in the context of the special relationship between doctors and patients or within family units. It then argues that communitarianism provides the better foundation for crafting infectious diseases control policies because contagious diseases, which often pass between perfect strangers, raise questions about the moral obligations we owe to (or are entitled to demand of) people with whom we share no "special" relationship. Accordingly, a socially embedded framework such as communitarianism may be a better fit for the more socially embedded ethical dilemmas of communicable diseases. PMID- 22084855 TI - Currents in contemporary bioethics: physicians' duty to inform patients of new medical discoveries: the effect of health information technology. PMID- 22084856 TI - Teaching health law: problem-based learning regarding "fractious problems" in health law: reflections on an educational experiment. PMID- 22084858 TI - Using symptom validity tests to detect malingered ADHD in college students. AB - Recently there has been growing concern that college students may feign symptoms of ADHD in order to obtain academic accommodations and stimulant medication. Unfortunately research has only begun to validate detection tools for malingered ADHD. The present study cross-validated the results of Sollman, Ranseen, and Berry (2010) on the efficacy of several symptom validity tests for detection of simulated ADHD among college students. Undergraduates with a history of diagnosed ADHD were randomly assigned either to respond honestly or exaggerate symptoms, and were compared to undergraduates with no history of ADHD or other psychiatric disorders who were also randomly assigned to respond honestly or feign symptoms of ADHD. Similar to Sollman et al. (2010) and other recent research on feigned ADHD, several symptom validity tests, including the Test of Memory Malingering (TOMM), Letter Memory Test (LMT), Digit Memory Test (DMT), Nonverbal Medical Symptom Validity Test (NV-MSVT), and the b Test were reasonably successful at discriminating feigned and genuine ADHD. When considered as a group, the criterion of failure of 2 or more of these SVTs had a sensitivity of. 475 and a specificity of 1.00. PMID- 22084860 TI - Nanotechnology is a major risk analysis issue. From the editors. PMID- 22084859 TI - XRCC1 399 Arg-related genotype and allele, but not XRCC1 His107Arg, XRCC1 Trp194Arg, KCNQ2, AT1R, and hOGG1 polymorphisms, are associated with higher susceptibility of endometriosis. AB - X-ray repair cross-complementing group 1 (XRCC1) and human 8-oxoguanine glycosylase 1 (hOGG1) play important roles in base excision repair. KCNQ genes comprising voltage-gated ion-channels related with cell stability. Angiotensin II type 1 receptor (AT1R) is related with angiogenesis, which influence endometriosis growth, invasion and regression. We aimed to investigate whether these polymorphisms were associated with endometriosis susceptibility. Women were divided [ 1 ]: endometriosis (n = 136 [ 2 ]); non-endometriosis groups (n = 112). XRCC1 (codon 107, 194, 399), hOGG1, KCNQ2, AT1R polymorphisms were amplified by PCR and detected by electrophoresis after restriction enzyme (RsaI, HpaII, MspI, Fnu4HI, Ava II, Dde I) digestions. Genotypes and allelic frequencies in both groups were compared. Proportions of XRCC1 Arg399Gln*GG/GA/AA and G/A allele between both groups were [ 1 ]: 41.9/53.7/4.4% and 68.8/31.2% [ 2 ]; 30.4/54.5/15.1% and 57.6/42.4% (p < 0.05). Other 5 polymorphisms (XRCC1 codon 107 and 194, hOGG1, KCNQ2, and AT1R) between both groups were non-significantly different. Proportions of XRCC1 107*AA/AG/GG and XRCC1 194*TT/TC/CC between both groups were [ 1 ]: 3.7/27.2/69.1% and 5.8/34.6/59.6% [ 2 ]; 2.6/21.4/75.8% and 11.6/37.5/50.9%. HOGG1*CC/CG/GG, KCNQ2*AA/AC/CCC and AT1R*AA/AC/CC were [ 1 ]: 14.8/42.6/42.6, 14/41.9/44.1 and 92.6/7.4/0% [ 2 ]; 11.6/50/38.4, 17/50/33 and 100/0/0%. We concluded that XRCC1 399 Arg-related genotype and allele are correlated with higher susceptibility to endometriosis, which suggested its association with endometriosis pathogenesis. XRCC1 107 and 194, hOGG1, KCNQ2, and AT1R are not associated with endometriosis susceptibility. PMID- 22084861 TI - Nanotechnology risk perceptions and communication: emerging technologies, emerging challenges. AB - Nanotechnology involves the fabrication, manipulation, and control of materials at the atomic level and may also bring novel uncertainties and risks. Potential parallels with other controversial technologies mean there is a need to develop a comprehensive understanding of processes of public perception of nanotechnology uncertainties, risks, and benefits, alongside related communication issues. Study of perceptions, at so early a stage in the development trajectory of a technology, is probably unique in the risk perception and communication field. As such it also brings new methodological and conceptual challenges. These include: dealing with the inherent diversity of the nanotechnology field itself; the unfamiliar and intangible nature of the concept, with few analogies to anchor mental models or risk perceptions; and the ethical and value questions underlying many nanotechnology debates. Utilizing the lens of social amplification of risk, and drawing upon the various contributions to this special issue of Risk Analysis on Nanotechnology Risk Perceptions and Communication, nanotechnology may at present be an attenuated hazard. The generic idea of "upstream public engagement" for emerging technologies such as nanotechnology is also discussed, alongside its importance for future work with emerging technologies in the risk communication field. PMID- 22084862 TI - A longitudinal study of newspaper and wire service coverage of nanotechnology risks. AB - This study reviewed coverage of nanotechnology risks in 20 U.S. and 9 U.K. newspapers and 2 wire services from 2000 to 2009. It focused on information that citizens could come across in daily newspaper reading that could highlight the salience of these issues and alert readers to potential risks. Few articles about nanotechnology health, environmental, and societal risks were found in these publications during this period, averaging only 36.7 per year for both countries. The coverage emphasized three main narratives over time: runaway technology, science-based studies, and regulation. Health risks were covered most frequently, followed by environmental and societal risk issues. Regulation coverage was not as frequent but increased over time. The majority of the coverage focused on news events and 10 events drew modest media attention. Scientific uncertainty discussions appeared in about half of the articles, and scientists and engineers were the dominant information sources in both countries. Some significant differences between U.S. and U.K. coverage were found: U.K. coverage emphasized more societal concerns, while U.S. coverage paid more attention to environmental risks. Because the volume of coverage was not extensive and was counterbalanced by many more articles extolling nanotechnology's benefits, it is questionable whether this coverage alerted readers about potential nanotechnology risks. Coupled with citizens' minimal knowledge about nanotechnology, this type of coverage could create public distrust of nanotechnology applications should a dangerous risk event occur. PMID- 22084863 TI - Labeling of nanotechnology consumer products can influence risk and benefit perceptions. AB - Currently, there is no mandatory labeling for products containing synthetic nanoparticles. The public as well as other stakeholders have positive views about mandatory labeling. However, little is known how such a label influences the risk and benefit perception of a product. Consumers may infer that a label is a signal that there are risks associated with this technology. Data were collected in a survey experiment (N= 1,382). Participants were randomly assigned to one of six conditions. The control group received a picture of a sunscreen container without a label. One experimental group received a picture of a sunscreen container with a label. The other groups received, in addition to the sunscreen container with a label, some risk or benefit information. Results suggest that labeling of products may reduce consumers' benefit perception and increase risk perception. Labeling nanotechnology consumer products may change the public perception of the products. Respondents may have relied on the affect heuristic for assessing the risks and benefits of the sunscreen. PMID- 22084864 TI - Evidence maps: communicating risk assessments in societal controversies: the case of engineered nanoparticles. AB - The transparent and fair characterization of scientific evidence for reporting the results of a hazard assessment is a demanding task. In this article, we present an approach for characterizing evidence--the evidence map approach. The theoretical starting point is to view evidence characterization as a form of argumentation. Thus, evidence maps are designed to depict the evidence base, the pro and con arguments, and the remaining uncertainties, which together lead experts to their conclusions when summarizing and evaluating the scientific evidence about a potential hazard. To illustrate its use, the evidence maps approach is applied to characterizing the health-relevant effects of engineered nanoparticles. Empirical data from an online survey suggests that the use of evidence maps improves the reporting of hazard assessments. Nonexperts prefer to receive the information included in an evidence map in order to come to an informed judgment. Furthermore, the benefits and limitations of evidence maps are discussed in the light of recent literature on risk communication. Finally, the article underlines the need for further research in order to increase quality of evidence reporting. PMID- 22084865 TI - The importance of stromal inflammation in squamous cell carcinoma of the tongue. AB - BACKGROUND: Histological risk assessment evaluating worst pattern of tumour invasion (WPOI), and lymphocytic response (LR), has previously been shown to be of prognostic significance in squamous cell carcinomas of the head and neck (SCCHN). SCCHN is a heterogeneous group of tumours including tumours located in the oral cavity, of which the majority is located in the tongue. METHODS: Haematoxylin/eosin-stained slides from diagnostic biopsies from 94 cases of SCC on the tongue were evaluated for WPOI and LR. Within the inflammatory infiltrate, the percentage of eosinophilic granulocytes was also estimated. Results were correlated with clinical data such as response to treatment and recurrence. RESULTS: For WPOI the majority of patients, 84%, showed small invasive tumours islands with a size <15 cells (grade 4). No correlation with survival, response to treatment or recurrence was seen for WPOI. More than half of the patients showed a dense lymphocytic infiltrate, a factor that was significantly correlated with complete response to radio therapy. Of the patients with dense lymphoid infiltrate, the majority, 63%, did not either have a recurrence. No significant correlation with recurrence, response to treatment or any other factor was seen for presence of eosinophils. CONCLUSIONS: Data clearly showed that tongue tumours have a split invasive growth pattern and an intense inflammatory response at the tumour interface. Results also indicated that evaluation of the intensity of the inflammatory infiltrate at the tumour interface in tongue SCC could provide information of potential importance for choice of treatment and prognosis. PMID- 22084866 TI - Histopathology of panniculitis--aspects of biopsy techniques and difficulties in diagnosis. AB - BACKGROUND: Clinical and histologic diagnosis of panniculitis may be difficult. The patients usually present with erythematous subcutaneous nodules with or without additional symptoms. If a skin biopsy does not include enough subcutaneous fat, histopathologic assessment is limited and the correct diagnosis may be delayed and require further sampling. PATIENTS AND METHODS: To illustrate the difficulties in the diagnosis of panniculitis, we performed a retrospective examination of four patients with different forms of panniculitis. RESULTS: In two patients with subcutaneous panniculitis-like T cell lymphoma and lupus panniculitis, the correct diagnosis could only be ascertained after a delay of several months because repeated biopsies had to be obtained throughout the course of disease. In two further patients with cold panniculitis and pancreatic panniculitis, clinicians did not even suspect an inflammatory process in the subcutaneous tissue. The correct diagnosis was made with a deep punch biopsy that included subcutaneous fat. CONCLUSIONS: On the one hand, these examples demonstrate the importance of sampling subcutaneous tissue when obtaining routine punch biopsies. On the other hand, in cases where the diagnosis is uncertain, it is necessary to perform large and deep incisional biopsies. PMID- 22084868 TI - The erosion of the family: A study of the fate of the family in Ghana. AB - Abstract In Ghana, as in other developing countries, it has been held that one cultural element acting towards the maintenance of high fertility has been the awareness that large families do more than small ones to ensure assistance to parents during sickness and especially during old age. The only experience known to the society of the fortunes of those in the latter condition is necessarily that of those who are already old and need such assistance. During 1963-64 a survey of 800 retired persons over 60 years of age was made in Ghana. Respondents of each sex were randomly selected within the urban southern rural and northern rural areas of the country. An examination was made of the effects of mortality and other factors in reducing the amount of possible assistance given by their children below the potential maximum determined by the original level of births. Differentials in fertility by area of present residence were discovered. It was shown that, although the average number of children supporting aged parents is greater in the case of large families, the extent of the assistance is not proportional to original family size, because of differentials in mortality, the chances of survivors reaching adulthood by their parents' old age, and the chances of adult survivors being able or willing to give such assistance. Only families who had between one and four children presented their parents with any considerable risk of receiving no help from their children. It was shown that there are grounds for conflict between the need for maximising assistance by having as many children as possible and by educating as many as possible. It was also shown that there is little evidence that parents consciously make such decisions in order to create an individual 'social welfare' system in that an extension of the state social welfare system would not, according to respondents, do much to change their views about desired family size. PMID- 22084867 TI - The Philadelphia Brief Assessment of Cognition (PBAC): a validated screening measure for dementia. AB - The Philadelphia Brief Assessment of the Cognition (PBAC) is a brief dementia screening instrument. The PBAC assesses five cognitive domains: working memory/executive control; lexical retrieval/language; visuospatial/visuoconstructional operations; verbal/visual episodic memory; and behavior/social comportment. A revised version of the PBAC was administered to 198 participants including patients with Alzheimer's disease (AD) (n=46) and four groups of patients with frontotemporal dementia (FTD) syndromes: behavioral variant FTD (bvFTD; n=65), semantic-variant primary progressive aphasia (PPA) (svPPA; n=22), non-fluent/agrammatic-variant PPA (nfaPPA; n=23), and corticobasal syndrome (CBS; n=42), and a group of normal controls (n=15). The total PBAC score was highly correlated with the MMSE. The criterion validity of the PBAC was assessed relative to standard neuropsychological test performance. Using standard neuropsychological test performance as a criterion, the total PBAC score accurately identified the presence and severity of dementia. Intra-class correlations between PBAC subscales and standard neuropsychological tests were highly significant. PBAC subscales demonstrated good clinical utility in distinguishing AD and FTD subtypes using receiver operating characteristic analysis and standard diagnostic performance statistics to determine optimal subscale cut scores. The PBAC is a valid tool and able to assesses differential patterns neuropsychological/behavioral impairment in a broad range of neurodegenerative conditions. PMID- 22084869 TI - The Americanization of catholic reproductive ideals. AB - Abstract This paper considers the attitude of Roman Catholics in the United States of America towards family size and suggests that large family ideals are still being put forward by the Church in publications and periodicals. The second part of the paper considers the attitudes of American Roman Catholics towards family size and shows that though there are indications that Roman Catholics regard slightly larger families as ideal than do members of other religions, the difference is not now very great. PMID- 22084870 TI - A study of internal migration in England and Wales. AB - Abstract The main trend in urban/rural migration is a continuous gain, in net terms, of towns from villages and large cities. But this is a result of two distinct migration streams associated with the process of family formation. While before marriage there is positive net migration from villages to both large cities and towns (and from large cities towards towns), after marriage there is a tendency for couples to move towards villages. This is explained by the desire of families, particularly those belonging to the middle class to move out of the urban centres to better accommodation in smaller communities. Considerable variations in migrations within and into regions are observed. These reflect the continuation oflong-term trends in internal migration (as described in Part I of this paper) in particular, population dispersal from Greater London and larger distance migration into the Southern and Eastern regions. Some social characteristics of migrants and non-migrants are compared. Associations between the intensity of internal migration on the one hand, and occupational status, education, social mobility and family size on the other are observed. An attempt is made to assess the extent of migration associated with the marriage process. Although this process increases mobility, its relative contribution to total adult mobility appears to be only slight. PMID- 22084871 TI - The AID computer programme, used to predict adoption of family planning in Koyang. AB - Abstract A highly useful computer programme has been developed for predicting values of a dependent variable. Basically a sequential analysis of variance, it creates a tree of two-way splits of the sample. Each split maximizes the reduction of unexplained variance in the dependent variable. The programme is remarkably sensitive to interactions, since it assumes neither linear relationships, normal distributions, nor homoscedasticity. This programme is put to work here on a prediction problem of administrative importance: which women in Korean villages will adopt family planning under a mild programme and under an intensive programme? Optimum predictors are identified and are arranged in a hierarchy of combinations which give progressively higher predictive accuracy. The best two or three predictors isolate large proportions of women with extremely low adoption rates. PMID- 22084872 TI - Fertility of the american negro in 1830 and 1850. AB - Abstract A comparison of the proportionate age distributions for negroes enumerated in the decennial censuses of the United States in the first half of the rorh century indicates that by 1850, negro fertility apparently had been declining for at least 20 years. This paper develops the relationship of the age distribution of a declining fertility population, where the decline has persisted for less than 25 years, to the stable population with the same current schedules of fertility and mortality. This relationship is used to estimate the negro birth rate and total fertility as of 1850. In turn, these estimates and the relationship of the age distributions of two stable populations with different fertility are used to estimate the negro birth rate and total fertility as of 1830. PMID- 22084873 TI - Migration and fertility in Puerto Rico. AB - Abstract In an investigation based on special tabulations of the 25 per cent sample from the 1960 Census of Population for Puerto Rico, it is found that migration experience tends to be associated with fertility for various marital statuses, including consensual unions, and for rural, urban and metropolitan residence. The findings cannot be attributed to variations in age composition among the various categories as age standardization and age-specificcomparisons yield similar results. However, it is also found that rural-urban and consensually-legally mated differentials in fertility cannot be accounted for by variations in the migration variables that are examined. Thus, consistently higher fertility is found for non-migrants than for migrants; for consensually mated than for legally married and for rural than for urban or metropolitan residents. With a single exception, women in consensual unions, fertility is lower for women in the San Juan metropolitan area than in the other urban areas. PMID- 22084874 TI - The effect of altitude on fertility in Andean countries. AB - Abstract In papers previously published in this journal J. M. Stycos and D. M. Heer have shown that fertility is lower in the economically underdeveloped Indian speaking parts of Peru, Ecuador and Bolivia than in the more prosperous Spanish speaking parts. Stycos concluded that the reason for the fertility difference in Peru is the greater marital instability of the Indian speakers which decreased their total exposure to the risk of conception. Heer suggested instead that the causes of the difference may be voluntary. The present paper questions Heer's analysis, and offers the explanation that the difference may be attributed to the physiological effects of altitude. PMID- 22084875 TI - Demographic and economic changes in the Sinkiang Uighur autonomous region. AB - Abstract The following characteristics of the population of Sinkiang are discussed: growth, stressing the importance of the immigration of Han Chinese; age-sex ratios; marital status; ethnic composition; education; health; and urbanisation. Economic development as it affects the composition of population, especiallyindustrial, agricultural and pastoral trends are also considered. A final section deals with the geo-political and demographic implications of the Sino-Soviet dispute. PMID- 22084876 TI - Summary statistics on indenture and associated migration affecting the West Indies, 1834-1918. AB - Abstract This paper presents summary statistics of immigration into the West Indies, under indenture or government sponsorship, during the period 1834-1918. The sources reveal a few discrepancies, but are sufficiently consistent to permit the construction of a series for each of the ethnic groups introduced. Most of the problems involved in constructing these series centre around the fact that a variety of sources have to be utilised. Immigration figures of East Indians, Portuguese, Chinese, Europeans and others into the several West Indian colonies have been prepared for each calendar year or season, but to conserve space are presented here in summary form. In the case of African immigration it is possible to give their country of origin. The only group of immigrants who were involved in return movements of any consequence are the East Indians. PMID- 22084887 TI - Peptide and protein quantitation by acid-catalyzed 18O-labeling of carboxyl groups. AB - We have developed a new method that applies acidic catalysis with hydrochloric acid for (18)O-labeling of peptides at their carboxyl groups. With this method, peptides get labeled at their C-terminus, at Asp and Glu residues, and at carboxymethylated cysteine residues. Oxygen atoms at phosphate groups of phosphopeptide are not exchanged. Our elaborated labeling protocol is easy to perform, fast (5 h and 30 min), and results in 95-97 atom % incorporation of (18)O at carboxyl groups. Undesired side reactions, such as deamidation or peptide hydrolysis, occur only at a very low level under the conditions applied. In addition, data analysis can be performed automatically using common software tools, such as Mascot Distiller. We have demonstrated the capability of this method for the quantitation of peptides as well as for phosphopeptides. PMID- 22084889 TI - Changing behaviours and continuing silence: sex in the post-immigration lives of mainland Chinese immigrants in Canada. AB - In China, reluctance to discuss sex continues to be widely observed despite the sexual revolution there. That silence generates questions about health risks in the contexts of HIV/AIDS and international migration. Based on a qualitative study of mainland Chinese immigrants in Canada, this paper explores the impacts of immigration processes on sex and sexuality. The findings reveal a gap between these individuals' changing sexual behaviours and the continuing silence on sex. Although Canada has exposed them to a new living environment that has shaped the dynamics and patterns of their sexual practices, their incomplete integration into the host society and their close connections with China as the home country mean that traditional Chinese norms continue to influence their understanding of these changes. With the increasing openness of these immigrants' sexual relationships, the obsolescence of their consciousness and knowledge of sexuality should be addressed in order to reduce their vulnerability to sexual inequalities and consequent health risks. PMID- 22084890 TI - Molecular length, monolayer density, and charge transport: lessons from Al AlOx/alkyl-phosphonate/Hg junctions. AB - A combined electronic transport-structure characterization of self-assembled monolayers (MLs) of alkyl-phosphonate (AP) chains on Al-AlOx substrates indicates a strong molecular structural effect on charge transport. On the basis of X-ray reflectivity, XPS, and FTIR data, we conclude that "long" APs (C14 and C16) form much denser MLs than do "short" APs (C8, C10, C12). While current through all junctions showed a tunneling-like exponential length-attenuation, junctions with sparsely packed "short" AP MLs attenuate the current relatively more efficiently than those with densely packed, "long" ones. Furthermore, "long" AP ML junctions showed strong bias variation of the length decay coefficient, beta, while for "short" AP ML junctions beta is nearly independent of bias. Therefore, even for these simple molecular systems made up of what are considered to be inert molecules, the tunneling distance cannot be varied independently of other electrical properties, as is commonly assumed. PMID- 22084891 TI - Relationship type, condom use and HIV/AIDS risks among men who have sex with men in six Chinese cities. AB - This study is the first to examine the role of partner type in sexual practices of men who have sex with men (MSM) in China. Using cross-sectional self administered questionnaires (N=692) with MSM in six Chinese cities (Shanghai, Guangzhou, Shenzhen, Xi'an, Dalian and Beijing) in 2008, this paper examines MSM's sexual practices, particularly condom use with different male and female partner types. We categorise sexual partner relationships into five types: partner/spouse, boyfriend/girlfriend, acquaintance, stranger and sex worker and hypothesise that the greater the affective distance between the partners, the greater the likelihood of engaging with intimate act and the lesser likelihood condom use. Results show that respondents had more MSM than heterosexual experiences. Relationships tended to be short-term, multiple (more than two) and concurrent (simultaneously two or more) principally with other men and to a lesser degree with women. Findings reveal that affective distance varied with partner types. Respondents performed more intimate acts (e.g., kissing, caressing) with intimate or stable partners (partner/spouse, boyfriend/girlfriend) than casual or unknown partners (acquaintance, stranger, sex worker). Condom use decreased when the affective distance with a partner increased. We conclude that partner type is a key factor of HIV infection among MSM in China; short-term, multiple and concurrent relationships are clear risk factors. Future research should focus on the subjective varied meanings of relationships, the idea of trust and the dynamics with different relationships to understand HIV infection of MSM in China. PMID- 22084892 TI - Physician-specific variation in medication adherence among diabetes patients. AB - OBJECTIVES: To examine the relationship that the patient has with his/her healthcare practitioner as a factor affecting medication adherence. STUDY DESIGN: Aggregate, physician-level adherence rates for patients were compared in a retrospective, non-case-controlled study of 3777 diabetes patients enrolled in a commercial pharmacy benefits program in a 6-county area in northeast Ohio. METHODS: Data for the top prescribing 200 physicians and their 3777 patients were analyzed based on the adherence of their patients to medications for diabetes, statins, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs). Physicians were then separated into adherence quartiles based on the results. Statistical tests for assessing between-group differences were performed. Results were reported for diabetes medication-specific adherence as well as adherence to statins and ACEIs/ARBs. RESULTS: No appreciable demographic differences were noted between patient or physician groups, including age, sex, race, cost share, and chronic medication use. Statistically significant differences in aggregate physician-specific medication adherence between the best performing and worst performing physician quartiles were identified, with medication adherence rates of 89.5% for the highest performing quartile compared with 68.1% for the lowest performing quartile. Medication adherence for statins and ACEIs/ARBs paralleled the results for diabetes medications: 88.4% versus 73.4% and 89.8% versus 76.9%, respectively. Importantly, significantly fewer patients in the lowest performing physician group had filled prescriptions for statins or ACEIs/ARBs. CONCLUSIONS: Physician-specific factors have an underappreciated impact on medication adherence. A better understanding of these factors may have substantial benefit in improving compliance with treatment and clinical outcomes. PMID- 22084893 TI - Ethnic differences in the development of albuminuria: the DISTANCE study. AB - OBJECTIVES: To determine whether ethnic differences in the incidence of albuminuria are present in patients with diabetes, and to identify social, behavioral, and provider factors that explain ethnic differences. STUDY DESIGN: Survey follow-up design with a race-stratified baseline survey (2005-2006) in diabetic patients from a nonprofit, fully integrated healthcare system in Northern California. We followed the 10,596 respondents (30% whites, 20% blacks, 23% Hispanics, 14% Asians, and 13% Filipinos) without evidence of prevalent albuminuria at baseline. METHODS: Incident albuminuria was defined by positive dipstick urinalysis (>1) or urine albumin to creatinine level (>30 mg/g), and confirmed with repeat testing at least 3 months later. RESULTS: The 27,292 person years of observation yielded 981 incident albuminuria events. Agestandardized rates of albuminuria (per 1000 person-years) ranged from 13.6 (95% confidence interval [CI] 10.5-17.0) in whites to 27.8 (CI 18.2- 38.3) in blacks. In fully adjusted Cox models, the hazard ratio for blacks (1.22, 95% CI 1.09-1.38), Asians (1.35, 95% CI 1.13-1.61), and Filipinos (1.93, 95% CI 1.61-2.32), but not Hispanics, was significantly greater than it was for whites. In some cases, point estimates changed markedly from the base model when fully adjusted for potential confounders. Moreover, adjustment for an array of potentially mediating factors explained only a small proportion of the observed ethnic disparities. CONCLUSIONS: Despite uniform medical care coverage, Filipinos, blacks, and Asians with diabetes developed albuminuria at higher rates than white and Hispanic adults. PMID- 22084894 TI - Compliance and persistence with concomitant statin and oral antihyperglycemic therapy. AB - OBJECTIVES: To compare compliance and persistence with statin and oral antihyperglycemic therapies in patients with type 2 diabetes who received concomitant therapy. STUDY DESIGN: Retrospective cohort study using a large US commercial claims database. METHODS: Patients with type 2 diabetes and dispensed prescriptions for both statin and oral antihyperglycemic therapies on the same date in 2006 (index date = first date of such dispensing) were included in the analysis (N = 52,414). Patients were required to have continuous enrollment in the database for 1 year prior to (baseline) and 2 years after (follow-up) index date. The 2-year medication possession ratio (MPR) was compared between statin and oral antihyperglycemic therapy. For the persistence analysis, treatment discontinuation was defined by a gap >30 days between the last date of supply from previous dispensing and subsequent refill. The likelihood of discontinuation of statin versus oral antihyperglycemic therapy was estimated by fitting a robust Cox proportional hazards regression model, adjusted for baseline variables. RESULTS: The 2-year MPR was 70% for statin and 78% for oral antihyperglycemic therapy (P <.0001). The proportion of patients with a 2-year MPR >80% was 52% for statin and 63% for oral antihyperglycemic therapy (P <.0001). The median time to discontinuation of statin was significantly shorter compared with oral antihyperglycemic therapy (284 vs 495 days, P <.001). There was a greater risk to discontinue statin than oral antihyperglycemic therapy (adjusted hazard ratio: 1.47 [95% confidence interval 1.45-1.48]). CONCLUSIONS: Compliance and persistence with statin therapy significantly lagged behind oral antihyperglycemic therapy in patients with type 2 diabetes who were treated concomitantly with both therapies. PMID- 22084895 TI - Persistence with biologic therapies in the Medicare coverage gap. AB - OBJECTIVES: To describe persistence with teriparatide and other biologic therapies in Medicare Part D plans with and without a coverage gap. STUDY DESIGN: Retrospective (2006) cohort study of Medicare Part D prescription drug plan beneficiaries from a large benefits company. Two plans with a coverage gap (defined as "basic") were combined and compared with a single plan with coverage for generic and branded medications (defined as "complete"). METHODS: Patients taking alendronate (nonbiologic comparator), teriparatide, etanercept, adalimumab, interferon beta-1a, or glatiramer acetate were selected for the study. For patients with complete coverage, equivalent financial thresholds were used to define the "gap."The definition of discontinuation was failure to fill the index prescription after reaching the gap. RESULTS: For alendronate, 27% of 133,260 patients had enrolled in the complete plan. Patients taking biologic therapies had more commonly enrolled in complete plans: teriparatide (66% of 6221), etanercept (58% of 1469), adalimumab (52% of 824), interferon beta-1a (60% of 438), and glatiramer acetate (53% of 393). For patients taking either alendronate or teriparatide, discontinuation rates were higher in the basic, versus complete, plan (adjusted odds ratios, 2.02 and 3.56, respectively). Discontinuation did not significantly vary by plan type for etanercept, adalimumab, interferon beta-1a, or glatiramer acetate. CONCLUSIONS: For patients who reached the coverage gap, discontinuation was more likely for patients taking osteoporosis (OP) medication. Not having a coverage gap was associated with improved persistence with OP treatment. PMID- 22084896 TI - Health information exchange among US hospitals. AB - OBJECTIVES: To determine the proportion of US hospitals engaged in health information exchange (HIE) with unaffiliated providers and to identify key hospital-level and market-level factors associated with participating in exchange. STUDY DESIGN: Using the 2009 American Hospital Association Information Technology survey, supplemented by Dartmouth Atlas, Area Resource File, and other national data, we examined which hospitals participated in regional efforts to electronically exchange clinical data. METHODS: We used logistic regression models to determine hospital-level characteristics and market-level characteristics associated with hospitals' likelihood of participating in HIE. RESULTS: We found that 10.7% of US hospitals engaged in HIE with unaffiliated providers. In communities where exchange occurred, for-profit hospitals and those with a small market share were far less likely to engage in HIE than nonprofit hospitals or those with a larger market share. Hospitals in more concentrated markets were more likely to exchange and hospitals in markets with higher Medicare spending were less likely to exchange. CONCLUSIONS: At the start of implementation of the Health Information Technology for Economic and Clinical Health (HITECH) Act, only a small minority of US hospitals electronically exchange clinical data with unaffiliated providers. Health information exchange is a key part of reforming the healthcare system, and factors related to competitiveness may be holding some providers back. PMID- 22084897 TI - Discrimination of three Pegaga (Centella) varieties and determination of growth lighting effects on metabolites content based on the chemometry of 1H nuclear magnetic resonance spectroscopy. AB - The metabolites of three species of Apiaceae, also known as Pegaga, were analyzed utilizing (1)H NMR spectroscopy and multivariate data analysis. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) resolved the species, Centella asiatica, Hydrocotyle bonariensis, and Hydrocotyle sibthorpioides, into three clusters. The saponins, asiaticoside and madecassoside, along with chlorogenic acids were the metabolites that contributed most to the separation. Furthermore, the effects of growth-lighting condition to metabolite contents were also investigated. The extracts of C. asiatica grown in full-day light exposure exhibited a stronger radical scavenging activity and contained more triterpenes (asiaticoside and madecassoside), flavonoids, and chlorogenic acids as compared to plants grown in 50% shade. This study established the potential of using a combination of (1)H NMR spectroscopy and multivariate data analyses in differentiating three closely related species and the effects of growth lighting, based on their metabolite contents and identification of the markers contributing to their differences. PMID- 22084898 TI - Site-specific incorporation of photo-cross-linker and bioorthogonal amino acids into enteric bacterial pathogens. AB - Enteric bacterial pathogens are known to effectively pass through the extremely acidic mammalian stomachs and cause infections in the small and/or large intestine of human hosts. However, their acid-survival strategy and pathogenesis mechanisms remain elusive, largely due to the lack of tools to directly monitor and manipulate essential components (e.g., defense proteins or invasive toxins) participating in these processes. Herein, we have extended the pyrrolysine-based genetic code expansion strategy for encoding unnatural amino acids in enteric bacterial species, including enteropathogenic Escherichia coli , Shigella , and Salmonella . Using this system, a photo-cross-linking amino acid was incorporated into a Shigella acid chaperone HdeA (shHdeA), which allowed the identification of a comprehensive list of in vivo client proteins that are protected by shHdeA upon acid stress. To further demonstrate the application of our strategy, an azide bearing amino acid was introduced into a Shigella type 3 secretion effector, OspF, without interruption of its secretion efficiency. This site-specifically installed azide handle allowed the facile detection of OspF's secretion in bacterial extracellular space. Taken together, these bioorthogonal functionalities we incorporated into enteric pathogens were shown to facilitate the investigation of unique and important proteins involved in the pathogenesis and stress-defense mechanisms of pathogenic bacteria that remain exceedingly difficult to study using conventional methodologies. PMID- 22084899 TI - Gram-scale synthesis of the A'B'-subunit of angelmicin B. AB - A gram-scale enantiospecific synthesis of the A'B'-subunit of angelmicin B is reported. The synthesis involves a Lewis acid catalyzed contrasteric Diels-Alder reaction and a tandem silyl zincate 1,6-addition/enolate oxidation sequence. PMID- 22084900 TI - Material nature versus structural nurture: the embodied carbon of fundamental structural elements. AB - The construction industry is under considerable legislative pressure to reduce its CO(2) emissions. The current focus is on operational CO(2) emissions, but as these are compulsorily reduced, the embodied CO(2) of structural components, overwhelmingly attributable to the material from which they are manufactured, will become of greater interest. Choice of structural materials for minimal embodied CO(2) is currently based either on subjective narrative arguments, or values of embodied CO(2) per unit volume or mass. Here we show that such arguments are invalid. We found that structural design parameters (dimensions, section choice, and load capacity) for fundamental structural components (simple beams and columns) are at least as important as material choice with regard to their effect on embodied CO(2) per unit load capacity per unit dimension, which can vary over several decades within and between material choices. This result demonstrates that relying on apparently objective analyses based on embodied CO(2) per unit volume or mass will not lead to minimum carbon solutions; a formal definition of the correct functional unit for embodied CO(2) must be used. In short, there is no such thing as a green structural material. PMID- 22084902 TI - N-heterocyclic carbene based ruthenium-catalyzed direct amide synthesis from alcohols and secondary amines: involvement of esters. AB - A well-defined N-heterocyclic carbene based ruthenium complex was developed as a highly active precatalyst for the direct amide synthesis from alcohols and secondary amines. Notably, reaction of 1-hexanol and dibenzylamine afforded 60% of the corresponding amide using our catalytic system, while no amide formation was observed for this reaction with the previously reported catalytic systems. Unlike the previously reported amidation with less sterically hindered alcohols and amines, involvement of ester intermediates was observed. PMID- 22084901 TI - Predicting carcinogenicity and understanding the carcinogenic mechanism of N nitroso compounds using a TOPS-MODE approach. AB - A linear discriminant analysis (LDA) coupled with an enhanced replacement method (ERM) was used as an alternative method to predict the carcinogenicity of N nitroso compounds (NOCs) in rats. This presented LDA based on the topological substructural molecular descriptors (TOPS-MODE) approach was developed to predict the carcinogenic and noncarcinogenic activity on a data set of 111 NOCs with a good classification value of 90.1%. The predictive power of the LDA model was validated through an external validation set (37 compounds) with a prediction accuracy of 94.6% and a leave-one-out cross-validation procedure (LOOCV) with a good prediction of 86.5%. This methodology showed that the TOPS-MODE descriptors weighted, respectively, by bond dipole moment and Abraham solute descriptor dipolarity/polarizability affected the NOC carcinogenicity. The contributions of certain bonds and fragments to carcinogenicity were used to assess biotransformation and carcinogenic mechanisms. The positive contribution of the carbon-nitrogen single bond (between the N-nitroso group and alpha-carbon to the N-nitroso group) indicated that the alpha-hydroxylation reaction could occur at the alpha-carbon or otherwise not occur. Similarly, the contributions from the molecular fragment could be applied to indicate whether the fragments generated an alkylating agent. These results suggested that this approach could discriminate between carcinogenic and noncarcinogenic NOCs, thereby providing insight into the structural features and chemical factors related to NOC carcinogenicity. PMID- 22084903 TI - Burning mouth syndrome: a therapeutic approach involving mechanical salivary stimulation. AB - OBJECTIVE: The study aimed to evaluate the effects of salivary stimulation therapy on the salivary flow, quality of saliva, and symptoms in patients with burning mouth syndrome (BMS). BACKGROUND: BMS is a chronic disorder characterized by a burning sensation. Some reports have proposed a role for saliva in the pathogenesis of BMS. METHODS: Twenty-six BMS patients underwent treatment with salivary mechanical stimulation. Resting and stimulated saliva were collected before and after therapy. Salivary levels of total protein, brain-derived neurotrophic factor, interleukin-10, tumor necrosis factor-alpha, interleukin-6, and nerve growth factor were assessed before and 90 days after therapy by enzyme linked immunosorbent assay. RESULTS: A significant reduction in the burning sensation and number of burning sites as well as an improvement of taste disturbances and xerostomia were observed after therapy. The salivary flow was not significantly modified. However, the therapy resulted in a significant decrease in salivary levels of total protein and an increase of tumor necrosis factor-alpha. CONCLUSION: Salivary mechanical stimulation therapy is effective in reducing clinical symptoms of BMS. PMID- 22084904 TI - Light microscopic hair shaft analysis in ectodermal dysplasia syndromes. AB - The objective of the study was to catalog hair shaft abnormalities in individuals with ectodermal dysplasia (ED) syndromes using light microscopy and to compare findings with those in unaffected controls. Light microscopy was performed in a nonblinded manner on hair shafts from 65 participants with seven types of ED (hypohidrotic ED, ED-ectrodactyly-cleft lip or palate, ankyloblepharon-ectodermal defects-cleft lip and palate, Clouston syndrome, Goltz syndrome, Schopf-Schulz Passarge syndrome, and oculodentodigital dysplasia) and 41 unaffected controls. Hair donations were collected at the 28th Annual National Family Conference held by the National Foundation for Ectodermal Dysplasia. Control participants were recruited from a private dermatology practice and an academic children's hospital outpatient dermatology clinic. Sixty-five affected participants and 41 unaffected controls were included in the analysis. We assessed the hair shafts of ED and control participants for abnormalities visible using LM. Light microscopy identified various pathologic hair shaft abnormalities in each type of ED, although none of the findings were statistically significantly different from those of the control group. Light microscopy is a poor adjuvant tool in the diagnosis of ED syndromes. Most findings are nonspecific and not sufficiently sensitive. PMID- 22084905 TI - Care coordinators: a controlled evaluation of an inpatient mental health service innovation. AB - The study aimed to evaluate the impact of introducing designated care coordinators into an acute mental health inpatient unit in terms of service delivery, clinical outcomes, and service user and significant other perceptions. A pre-post-controlled design was implemented with a consecutive sample of 292 service users admitted and staying more than 5 days in two wards, with care coordinators introduced in one ward. Data were obtained from clinical records, standard measures, and service user and significant other surveys. Care coordinator input was associated with significant improvements in service delivery and stronger involvement of significant others and community resources. Care-coordinated clients showed significantly better clinical outcomes, including the Health of Nations Outcome Scales behaviour subscale, less time in the intensive care subunit, less community crisis team input in the week following discharge, and lower rates of readmission in the month following discharge. Care coordinated service users and their significant others gave higher ratings of service delivery, outcome, and satisfaction. The results indicate that designated care coordinators significantly improve care processes, outcomes, and service user experience in acute inpatient mental health settings. PMID- 22084906 TI - Matrix metalloproteinases in plants: a brief overview. AB - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases belonging to the metzincin clan. MMPs have been characterized in detail in mammals, and they have been shown to play key roles in many physiological and pathological processes. Plant MMP-like proteases exist, but relatively few have been characterized. It has been speculated that plant MMPs are involved in remodeling of the plant extracellular matrix during growth, development and stress response. However, the precise functions and physiological substrates in higher plants remain to be determined. In this brief overview, we summarize the current knowledge of MMPs in higher plants and algae. PMID- 22084907 TI - Differential activation of proapoptotic molecules between mouse and rat models of distal motor trigeminal denervation. AB - BACKGROUND: We previously developed a rat trigeminal motor neuron axotomy model involving masseter and temporal muscle resection to study pathological changes of the central nucleus after peripheral nerve injury caused by oral surgery. Because motor neurons are reported to be more vulnerable to axotomy in mice than rats, we compared the degeneration process of the trigeminal motor nucleus in the rat model with a similar mouse model. METHODS: We removed masseter and temporal muscles of adult mice or rats. Animals were sacrificed at 3, 7, 14, 28, 42, and 56 days post-operation, and the trigeminal motor nuclei were histologically analyzed. RESULTS: Size reduction, but no neuronal loss, was seen in the trigeminal motor nuclei in both mice and rats. Time-dependent Noxa expression, starting at 1 week post-operation (wpo), was seen in the mouse model. By 8 wpo, mice expressed a higher level of Noxa than rats. Additionally, we noted persistent expression of cleaved caspase-3 in mice but not in rats. Conversely, apoptosis-inducing factor (AIF), which executes DNA fragmentation in the nucleus, was not translocated to the nucleus in either model. CONCLUSIONS: Our findings indicate differential activation of motor neuron apoptosis pathways after axotomy in mice and rats. Lack of activation of caspase-independent pathways and distal end denervation in our model might be related to the survival of motor neurons after axonal injury. These findings could be relevant to future neuroprotective strategies for peripheral nerve injury caused by oral surgeries. PMID- 22084908 TI - The decline of fertility: Innovation or adjustment process. AB - Abstract In Western society the process of fertility decline is often regarded as an innovation process. The assumptions behind this approach seem rather questionable, and the diffusion lags or gradients of limited importance. Both Swedish and other European data are used as illustrations. It is suggested that the decline be treated within the wider sociological perspective of a time consuming adjustment or change process, not necessarily starting from a position of completely uncontrolled fertility within marriage. The situation in to-day's high fertility populations is briefly discussed against this background. PMID- 22084909 TI - Malthus on norway. AB - Abstract Malthus visited Norway in 1799 and his impression of the country's demographic experience was important in determining the character of the second edition of his Essay on the Principle of Population. He relied for the most part on non-statistical sources. This led him to exaggerate, e.g. the size of households, the number of unmarried farm servants and to miss important features, e.g. differences in marital age patterns, regional variations in fertility and nuptiality. The bias of his itinerary and of his main informants is also apparent. Statistical material not available to Malthus indicates that he was right to stress the late age at marriage in Norway but wrong to ignore the operation of the positive check. Mortality was frequently high in late eighteenth and early nineteenth-century Norway, much higher than Malthus ever realized. This destroys the symmetry, as well as the morality, of Malthus's exposition. PMID- 22084910 TI - Economic considerations in family growth decisions. AB - Abstract Examination of the fertility patterns of a sample of white Detroit couples at selected stages of the family life cycle indicates that, in a large American metropolis, family income is more closely related to the time when a family is formed and has its children than to the number of children it expects to have. In a longitudinal study, current income is strongly related to the timing of demographic events-the age at marriage, whether pre-maritally pregnant, the time interval from marriage to a given parity, and fertility during a two year follow-up period. This paper also explores the hypothesis that a family's evaluation of its economic position and the choices it makes about important family expenditures has a relation to fertility apart from the family's objective current income level. Couples who consider their income adequate for their needs or relatively greater than that of their friends or peers, and those who expect substantial increases in the future, tend to expect more children than those who do not. Small but consistent differences obtain over the parities studied. Variables indexing alternative family expenditure patterns, such as cars, or savings for college education for children, are associated with lower family size expectations and longer spacing patterns. PMID- 22084911 TI - Parameters of the menstrual cycle: A reply. AB - Abstract In a set of two papers, one of them published in this journal in July 1965, W. H. James defends the menstrual statistics of E. J. Farris and his co workers and exploits these data to propose a new formula of calendar rhythm that allegedly provides maximum protection for a given amount of abstinence. The present paper argues that Farris's data are open to a suspicion of serious bias. James's estimates ofvarious parameters of the menstrual cycle are questioned mainly on grounds of deficient data. However, it is concluded that his methods of estimation will prove useful in future analyses of menstrual variation. PMID- 22084912 TI - Bridal pregnancy in rural England in earlier centuries. AB - Abstract A sample of 3,786 marriages, recorded in the parish registers of 77 rural and semi-rural parishes in 24 English counties during the period 1540-1835, is investigated. 49% of the marriages can be followed through to a maternity recorded in a baptism-entry in the baptism register of the same parish, i.e. the parish of marriage. Of these brides traced to a maternity, roughly one-third had their maternity recorded within eight and a half months of marriage and were therefore probably pregnant at marriage. When allowance is made for delayed baptisms, and for brides whose pre-maritally conceived pregnancy terminated in an abortion or stillbirth and hence went unrecorded, the proportion of 'traced' brides pregnant may approach one-half. Turning to the 51% of marriages untraced to maternities in this investigation, for a large number (perhaps two-thirds) the most likely explanation is the removal ofthe married couple from the parish of marriage before maternity occurred, for reasons unconnected with the bridal condition. It is concluded that there is direct and detailed evidence in the parish registers that more than one-sixth of all brides were pregnant at marriage, and that it can be reasonably deduced from the direct evidence that in fact about one-third were pregnant. The proportion of brides pregnant in the earlier centuries (before 1700) appears to have been only about one-half of that in the later centuries. Regionally, the highest rate in both periods appears to have been in the northern four counties. The social interpretation of these bridal pregnancy rates poses many problems for the social historian. PMID- 22084913 TI - On the probable age structure of the Roman population. AB - Abstract The average expectation of life has often been calculated from ages given on the many thousands of surviving Roman tombstones. But the distribution of these ages at death is demographically most improbable. However, this can be easily explained once attention is paid to the patterns of commemoration between relatives, for in some inscriptions the age at death is given, in others a relationship (e.g. marriage) is commemorated, in yet others both are recorded. But the distortions cannot be corrected; these ages at death must be discarded as useful evidence for estimating life expectation. PMID- 22084916 TI - Detection and identification of plasma bacterial and viral elements in HIV/AIDS patients in comparison to healthy adults. AB - A low level of CD4+ lymphocyte cells makes end-stage HIV/AIDS patients highly susceptible to microbial infections. We have adopted the next generation sequencing method to identify the spectrum of bacterial plasma and viral elements that might be present in these patients. The HIV/AIDS plasma microbiome was dominated by bacterial elements in the taxonomical order Pseudomonadales, while healthy people carried fewer bacterial DNA in the plasma. We have found that many of the bacterial elements in HIV/AIDS plasma are similar to those of the microbes found in the human gut, suggesting potential acquisition of microbial elements from the gut. The HIV/AIDS and normal plasma DNA virome shared some similarities in the presence of common ubiquitous eukaryotic viruses. The normal DNA virome was mainly composed of viruses from Anelloviridae. In contrast, the HIV/AIDS DNA virome contained a large proportion of bacteriophages, endogenous retroviruses and a non-human virus. In addition, several sequences, which might belong to novel bacteria or endogenous retroviruses, were identified. Taken together, the use of high-throughput sequencing technology in unveiling microbial metagenomics may facilitate future research in combating HIV/AIDS and its associated microbial complications. PMID- 22084917 TI - Improving wound score classification with limited remission spectra. AB - The classification of wounds into healing states depending on their absorption spectrum of visible and near infrared light remains an important task in dermatology. Moreover, a reduction of the spectrum that is used in the classification task to fewer but important wavelengths is desirable, as each measured wavelength increases the examination costs without necessarily providing further information to the classification of wound healing states. This paper addresses two aspects: First the improvement of the classification of wounds into healing states and second, a cost reduction by choosing only important wavelengths. Standard Data Mining methods are evaluated for their classification accuracy (CA) and compared to their performance when applying feature selection techniques that are used to reduce the amount of necessary wavelengths. The results indicate that the 1-nearest-neighbor approach (IB1 algorithm) comes up with the best CA, while only relying on a fraction (4%) of the standard wavelength spectrum. PMID- 22084918 TI - Shaking a hornets' nest: pitfalls of abortion counselling in a secular constitutional order--a view from South Africa. AB - There exists an enormous gulf between the aspirations of South Africa's abortion legislation--among the most liberal in the world--and its implementation. One weakness in the provision of abortion services in South Africa is the absence of comprehensive abortion counselling services. On the face of it, the idea that counselling ought, as a matter of course, to be a significant component of a country's termination of pregnancy service provision, seems both straightforwardly sensible and politically innocent. This paper describes how abortion counselling has historically, in many different contexts, been saturated with questionable assumptions about women and their bodies. Counselling has more often than not been deployed, either as the formal policy of states or through informal mechanisms, as a means of curbing the right to abortion rather than deepening the meaning of that right. Differing approaches to counselling emerge as a reflection of contestations over reproductive and gender politics. Specifying an appropriate model for the provision of state-sponsored abortion counselling in the public health sector of a secular constitutional state provokes more of a hornet's nest of dilemmas than is sometimes supposed. PMID- 22084919 TI - Assessing the impact of the duration and intensity of inhalation exposure on the magnitude of the variability of internal dose metrics in children and adults. AB - The objective of this study was to assess the impact of the exposure duration and intensity on the human kinetic adjustment factor (HKAF). A physiologically based pharmacokinetic model was used to compute target dose metrics (i.e. maximum blood concentration (C(max)) and amount metabolized/L liver/24 h (Amet)) in adults, neonates (0-30 days), toddlers (1-3 years), and pregnant women following inhalation exposure to benzene, styrene, 1,1,1-trichloroethane and 1,4-dioxane. Exposure scenarios simulated involved various concentrations based on the chemical's reference concentration (low) and six of U.S. EPA's Acute Exposure Guideline Levels (AEGLs) (high), for durations of 10 min, 60 min, 8 h, and 24 h, as well as at steady-state. Distributions for body weight (BW), height (H), and hepatic CYP2E1 content were obtained from the literature or from P3M software, whereas blood flows and tissue volumes were calculated from BW and H. The HKAF was computed based on distributions of dose metrics obtained by Monte Carlo simulations [95th percentile in each subpopulation/median in adults]. At low levels of exposure, ranges of C(max)-based HKAF were 1-6.8 depending on the chemical, with 1,4-dioxane exhibiting the greatest values. At high levels of exposure, this range was 1.1-5.2, with styrene exhibiting the greatest value. Neonates were always the most sensitive subpopulation based on C(max), and pregnant women were most sensitive based on Amet in the majority of the cases (1.3-2.1). These results have shown that the chemical-specific HKAF varies as a function of exposure duration and intensity of inhalation exposures, and sometimes exceeds the default value used in risk assessments. PMID- 22084925 TI - Deceptive examinees who committed suicide: report of two cases. AB - Deceptive behavior by neuropsychological examinees does not preclude the presence of significant psychopathology. To illustrate this fact we present two cases. Case 1 had a diagnosis of factitious disorder and clear evidence on neurological and neuropsychological exams of exaggeration. Case 2 had a somatoform disorder and provided a deceptive social history. Long after the neuropsychological evaluations, both persons committed suicide. These cases provide anecdotal evidence that deceptive behavior does not preclude the presence of serious psychopathology, and that deceptive behavior and self-destructive behavior sometimes coincide. PMID- 22084926 TI - Population genetic segmentation of MHC-correlated perfume preferences. AB - It has become difficult to find a matching perfume. An overwhelming number of 300 new perfumes launch each year, and marketing campaigns target pre-defined groups based on gender, age or income rather than on individual preferences. Recent evidence for a genetic basis of perfume preferences, however, could be the starting point for a novel population genetic approach to better match perfumes with people's preferences. With a total of 116 participants genotyped for alleles of three loci of the major histocompatibility complex (MHC), the aim of this study was to test whether common MHC alleles could be used as genetic markers to segment a given population into preference types. Significant deviations from random expectations for a set of 10 common perfume ingredients indicate how such segmentation could be achieved. In addition, preference patterns of participants confronted with images that contained a sexual communication context significantly differed in their ratings for some of the scents compared with participants confronted with images of perfume bottles. This strongly supports the assumption that genetically correlated perfume preferences evolved in the context of sexual communication. The results are discussed in the light of perfume customization. PMID- 22084927 TI - Mechanism for singlet fission in pentacene and tetracene: from single exciton to two triplets. AB - Singlet fission (SF) could dramatically increase the efficiency of organic solar cells by producing two triplet excitons from each absorbed photon. While this process has been known for decades, most descriptions have assumed the necessity of a charge-transfer intermediate. This ab initio study characterizes the low lying excited states in acene molecular crystals in order to describe how SF occurs in a realistic crystal environment. Intermolecular interactions are shown to localize the initially delocalized bright state onto a pair of monomers. From this localized state, nonadiabatic coupling mediated by intermolecular motion between the optically allowed exciton and a dark multi-exciton state facilitates SF without the need for a nearby low-lying charge-transfer intermediate. An estimate of the crossing rate shows that this direct quantum mechanical process occurs in well under 1 ps in pentacene. In tetracene, the dark multi-exciton state is uphill from the lowest singlet excited state, resulting in a dynamic interplay between SF and triplet-triplet annihilation. PMID- 22084928 TI - Functionalization of a self-assembled monolayer driven by low-energy electron exposure. AB - Self-assembled monolayers (SAMs) of 10-undecene-1-thiol on Au were functionalized with nitrogen-containing groups using an approach in which multilayer ammonia (NH(3)) films were deposited at low temperature onto the SAMs and subsequently exposed to 15 eV electrons. The result of this process was investigated after removal of the remaining NH(3) by annealing to room temperature using high resolution electron energy loss spectroscopy (HREELS) and X-ray photoelectron spectroscopy (XPS). HREELS shows that the CC double bonds disappear during electron exposure, while XPS gives evidence that about 25% of the terminal double bonds of the SAM were functionalized. Also, XPS shows that a sufficiently thick NH(3) layer protects the underlying SAM from electron-induced damage. The process suggested here thus represents a particularly gentle approach to the functionalization of ultrathin molecular layers. Thermal desorption spectrometry (TDS) and electron-stimulated desorption (ESD) experiments on condensed layers of NH(3) reveal production of N(2) but show that significant amounts of the initial NH(3) as well as N(2) produced during electron exposure desorb. Hydrogen released upon formation of N(2) is held responsible for the reduction of double bonds and protection of the SAMs from damage. PMID- 22084929 TI - Solution NMR approaches for establishing specificity of weak heterodimerization of membrane proteins. AB - Solution NMR provides a powerful approach for detecting complex formation involving weak to moderate intermolecular affinity. However, solution NMR has only rarely been used to detect complex formation between two membrane proteins in model membranes. The impact of specific binding on the NMR spectrum of a membrane protein can be difficult to distinguish from spectral changes that are induced by nonspecific binding and/or by changes that arise from forced cohabitation of the two proteins in a single model membrane assembly. This is particularly the case when solubility limits make it impossible to complete a titration to the point of near saturation of complex formation. In this work experiments are presented that provide the basis for establishing whether specific complex formation occurs between two membrane proteins under conditions where binding is not of high avidity. Application of these methods led to the conclusion that the membrane protein CD147 (also known as EMMPRIN or basigin) forms a specific heterodimeric complex in the membrane with the 99-residue transmembrane C-terminal fragment of the amyloid precursor protein (C99 or APP betaCTF), the latter being the immediate precursor of the amyloid-beta polypeptides that are closely linked to the etiology of Alzheimer's disease. PMID- 22084930 TI - Quantitative spectroscopic analysis of heterogeneous mixtures: the correction of multiplicative effects caused by variations in physical properties of samples. AB - Spectral measurements of complex heterogeneous types of mixture samples are often affected by significant multiplicative effects resulting from light scattering, due to physical variations (e.g., particle size and shape, sample packing, and sample surface, etc.) inherent within the individual samples. Therefore, the separation of the spectral contributions due to variations in chemical compositions from those caused by physical variations is crucial to accurate quantitative spectroscopic analysis of heterogeneous samples. In this work, an improved strategy has been proposed to estimate the multiplicative parameters accounting for multiplicative effects in each measured spectrum and, hence, mitigate the detrimental influence of multiplicative effects on the quantitative spectroscopic analysis of heterogeneous samples. The basic assumption of the proposed method is that light scattering due to physical variations has the same effects on the spectral contributions of each of the spectroscopically active chemical components in the same sample mixture. On the basis of this underlying assumption, the proposed method realizes the efficient estimation of the multiplicative parameters by solving a simple quadratic programming problem. The performance of the proposed method has been tested on two publicly available benchmark data sets (i.e., near-infrared total diffuse transmittance spectra of four-component suspension samples and near-infrared spectral data of meat samples) and compared with some empirical approaches designed for the same purpose. It was found that the proposed method provided appreciable improvement in quantitative spectroscopic analysis of heterogeneous mixture samples. The study indicates that accurate quantitative spectroscopic analysis of heterogeneous mixture samples can be achieved through the combination of spectroscopic techniques with smart modeling methodology. PMID- 22084932 TI - Vacuum cleaner emissions as a source of indoor exposure to airborne particles and bacteria. AB - Vacuuming can be a source of indoor exposure to biological and nonbiological aerosols, although there are few data that describe the magnitude of emissions from the vacuum cleaner itself. We therefore sought to quantify emission rates of particles and bacteria from a large group of vacuum cleaners and investigate their potential determinants, including temperature, dust bags, exhaust filters, price, and age. Emissions of particles between 0.009 and 20 MUm and bacteria were measured from 21 vacuums. Ultrafine (<100 nm) particle emission rates ranged from 4.0 * 10(6) to 1.1 * 10(11) particles min(-1). Emission of 0.54-20 MUm particles ranged from 4.0 * 10(4) to 1.2 * 10(9) particles min(-1). PM(2.5) emissions were between 2.4 * 10(-1) and 5.4 * 10(3) MUg min(-1). Bacteria emissions ranged from 0 to 7.4 * 10(5) bacteria min(-1) and were poorly correlated with dust bag bacteria content and particle emissions. Large variability in emission of all parameters was observed across the 21 vacuums, which was largely not attributable to the range of determinant factors we assessed. Vacuum cleaner emissions contribute to indoor exposure to nonbiological and biological aerosols when vacuuming, and this may vary markedly depending on the vacuum used. PMID- 22084931 TI - Common variants in FTO are not significantly associated with obesity-related phenotypes among Samoans of Polynesia. AB - The association between obesity and the fat mass and obesity-associated (FTO) gene has been widely replicated among Caucasian populations. The limited number of studies assessing its significance in Asian populations has been somewhat conflicting. We performed a genetic association study of 51 tagging, genome-wide association studies, and imputed single nucleotide polymorphisms with 12 measures of adiposity and skeletal robustness in two Samoan populations of Polynesia. We included 465 and 624 unrelated American Samoan and Samoan individuals, respectively; these populations derive from a single genetic background traced to Southeast Asia and represent one sociocultural unit, although they are economically disparate with distinct environmental exposures. American Samoans were significantly larger than Samoans in all measures of obesity and most measures of skeletal robustness. In separate analyses of American Samoa and Samoa, we found a total of 36 nominal associations between FTO variants and skeletal and obesity measures. The preponderance of these nominal associations (32 of 36) was observed in the Samoan population, and predominantly with skeletal rather than fat mass measures (28 of 36). All significance disappeared, however, following corrections for multiple testing. Based on these findings, it could be surmised that FTO is not likely a major obesity locus in Polynesian populations. PMID- 22084933 TI - Quality of life among Brazilian women living with HIV/AIDS. AB - The purpose of the present study was to assess quality of life (QoL) in Brazilian women living with HIV/AIDS, according to the World Health Organization Quality of Life HIV-BREF (WHOQoL-HIV-BREF) domains. A quantitative-based, cross-sectional, analytical study was carried out in healthcare centers specialized in assisting people living with HIV/AIDS, located in a municipality of the state of Sao Paulo, Brazil. One hundred and six women of age 18 years or more, users of the public healthcare system, participated in the study. Socio-demographic and clinical variables were collected using a specific questionnaire. Quality of life related variables were collected by means of the WHOQoL-HIV-BREF instrument. As per the QoL domains, study results show that the Spirituality domain reached a standardized mean score of 65.7, followed by the Physical (64.7), Psychological (60.6), Social Relationships (59.5), Independence (58.6), and Environment (54.5) domains. Results of the multiple regression analysis indicate that the women's employment or retirement, income greater than the minimum wage, and higher educational level were associated with a higher standardized mean score of QoL. However, recent HIV/AIDS diagnosis and exposure to antiretroviral agents for a period shorter than two years were negatively associated with QoL. It is critical that public policies favor an all-embracing social inclusion of these women, thus promoting better social conditions. Counseling, clinical follow-up immediately after the infection diagnosis, and initiation of antiretroviral treatment are crucial moments in the lives of these individuals. PMID- 22084934 TI - Molecular mechanism of glyceraldehyde-3-phosphate dehydrogenase inactivation by alpha,beta-unsaturated carbonyl derivatives. AB - alpha,beta-Unsaturated carbonyls make up an important class of chemicals involved in environmental toxicity and disease processes. Whereas adduction of cysteine residues on proteins is a well-documented reaction of these chemicals, such a generic effect cannot explain the molecular mechanism of cytotoxicity. Instead, more detailed information is needed regarding the possible specificity and kinetics of cysteine targeting and the quantitative relationship between adduct burden and protein dysfunction. To address these data gaps, we incubated purified human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with acrylamide (ACR), acrolein, or methylvinyl ketone (MVK). Results show that these alpha,beta unsaturated carbonyl toxicants inhibited GAPDH activity in a concentration- and time-dependent manner. The rank order of enzyme inhibition (K(I)) (i.e., ACR ? MVK < acrolein) was related to the calculated electrophilic reactivity of each compound and to the corresponding kinetics of cysteine adduct formation. Tandem mass spectrometry revealed that adduct formation was selective at lower concentrations; i.e., ACR preferentially formed adducts with Cys152 (residues 146 162). At higher concentrations, ACR also formed adducts with Cys156 and Cys247 (residues 235-248). Adduct formation at Cys152 was correlated to enzyme inhibition, which is consistent with the regulatory role of this residue in enzyme function and its location within the GAPDH active site. Further analyses indicated that Cys152 was present in a pK(a)-lowering microenvironment (pK(a) = 6.03), and at physiological pH, the corresponding sulfhydryl group exists in the highly reactive nucleophilic thiolate state. These data suggest a general cytotoxic mechanism in which electrophilic alpha,beta-unsaturated carbonyls selectively form adducts with reactive nucleophilic cysteine residues specifically associated with the active sites of proteins. These specialized cysteine residues are toxicologically relevant molecular targets, because chemical derivatization causes loss of protein function. PMID- 22084935 TI - Abnormal actin binding of aberrant beta-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy. AB - NM (nemaline myopathy) is a rare genetic muscle disorder defined on the basis of muscle weakness and the presence of structural abnormalities in the muscle fibres, i.e. nemaline bodies. The related disorder cap myopathy is defined by cap like structures located peripherally in the muscle fibres. Both disorders may be caused by mutations in the TPM2 gene encoding beta-Tm (tropomyosin). Tm controls muscle contraction by inhibiting actin-myosin interaction in a calcium-sensitive manner. In the present study, we have investigated the pathogenetic mechanisms underlying five disease-causing mutations in Tm. We show that four of the mutations cause changes in affinity for actin, which may cause muscle weakness in these patients, whereas two show defective Ca2+ activation of contractility. We have also mapped the amino acids altered by the mutation to regions important for actin binding and note that two of the mutations cause altered protein conformation, which could account for impaired actin affinity. PMID- 22084936 TI - Identification of splice variants, targeted microRNAs and functional single nucleotide polymorphisms of the BOLA-DQA2 gene in dairy cattle. AB - Major histocompatibility complex, class II, DQ alpha 2, also named BOLA-DQA2, belongs to the Bovine Leukocyte Antigen (BOLA) class II genes which are involved in the immune response. To explore the variability of the BOLA-DQA2 gene and resistance to mastitis in cows, the splice variants (SV), targeted microRNAs (miRNAs), and single nucleotide polymorphisms (SNPs) were identified in this study. A new SV (BOLA-DQA2-SV1) lacking part of exon 3 (195 bp) and two 3' untranslated regions (UTR) (52 bp+167 bp) of the BOLA-DQA2 gene was found in the healthy and mastitis-infected mammary gland tissues. Four of 13 new SNPs and multiple nucleotide polymorphisms resulted in amino acid changes in the protein and SNP (c. +1283 C>T) may affect the binding to the seed sequence of bta-miR 2318. Further, we detected the relative expressions of two BOLA-DQA2 transcripts and five candidated microRNAs binding to the 3'-UTR of two transcripts in the mammary gland tissues in dairy cattle by using the quantitative real-time polymerase chain reaction. The result showed that expression of the BOLA-DQA2-SV1 mRNA was significantly upregulated 2.67-fold (p<0.05) in mastitis-infected mammary tissues (n = 5) compared with the healthy mammary gland mammary tissues (n = 5). Except for bta-miR-1777a, miRNA expression (bta-miR-296, miR-2430, and miR-671) was upregulated 1.75 to 2.59-fold (p<0.05), whereas miR-2318 was downregulated in the mastitis cows. Our findings reveal that BOLA-DQA2-SV1 may play an important role in the mastitis resistance in dairy cattle. Whether the SNPs affect the structure of the BOLA-DQA2 gene or association with mastitis resistance is unknown and warrants further investigation. PMID- 22084937 TI - Modulator effects of the methylenetetrahydrofolate reductase C677T polymorphism on response to vitamin B12 therapy and homocysteine metabolism. AB - In this study, our aim was to investigate the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on the vitamin B12 therapy response in 95 patients with vitamin B12 deficiency and 92 healthy control subjects using vitamin B12, plasma total homocysteine (tHcy), and folate as the main measure of outcome. MTHFR C677T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism techniques. There were no differences in the distribution of MTHFR genotypes in the cases versus the controls. Mean concentrations of plasma tHcy and B12 vitamin were 18.84 MUM and 142.47 pg/mL in patients with TT (10.5%) genotypes. Furthermore, mean concentrations of B12 vitamin after cobalamin therapy were 697.62, 656.64, and 488.76 pg/mL in patients with the CC, CT, and TT genotypes, respectively. The MTHFR 677 TT genotype has decreasing effect in B12 vitamin and increasing effect in tHcy. In comparison with the patients having CC and CT genotypes, patients with the TT genotype had a lower response to vitamin B12 therapy. PMID- 22084938 TI - Association between VHL single nucleotide polymorphism (rs779805) and the susceptibility to prostate cancer in Chinese. AB - The Von Hippel-Lindau (VHL) tumor suppressor gene is a crucial regulator of the hypoxia response pathway and plays an important role in tumorigenesis, particularly in tumor growth and vascularization. We hypothesize that polymorphisms in the functional region of VHL may influence susceptibility to prostate cancer (PCa). We genotyped a potentially functional polymorphism (rs779805) in 5' UTR region of VHL in a case-control study of 665 PCa patients and 715 cancer-free controls in a Chinese population using the Taqman assay. The genetic associations between the incidence and progression of PCa were assessed by logistic regression. We observed that the rs779805 A>G polymorphism was significantly associated with risk for PCa. Compared with the AA genotype, the AG and AG/GG genotypes were associated with decreased risk of PCa (adjusted odds ratio [OR]=0.79, 95% confidence interval [CI]=0.62-0.99, and adjusted OR=0.76, 95% CI=0.61-0.95, respectively). Further, this decreased risk was more pronounced in the subgroups of nonsmokers (OR=0.73, 95% CI=0.54-0.98), nondrinkers (OR=0.70, 95% CI=0.54-0.91) and patients without family history of cancer (OR=0.72, 95% CI=0.57-0.92). In addition, the decreased risk associated with rs779805 variant genotypes (AG/GG) was more pronounced among the prostate specific antigen (PSA)>20 ng/mL subgroup (OR=0.68, 95% CI=0.49-0.95). Our findings suggest that the rs779805 A>G polymorphism in VHL may confer susceptibility to PCa in the Chinese population. PMID- 22084939 TI - An organocascade kinetic resolution. AB - Products of a novel iminium-catalyzed oxa-Michael addition undergo a kinetic resolution by a subsequent enamine-catalyzed intermolecular reaction. This is a rare example of kinetic resolution by enamine catalysis and the first organocascade kinetic resolution. This resolution produces enantioenriched 2,6 cis-tetrahydropyrans and, notably, cascade products with absolute and relative configurations normally not observed using this diphenyl prolinol silyl ether. This resolution thus provides new insight into asymmetric induction in reactions employing this catalyst. PMID- 22084940 TI - Determining milk isolated and conjugated trans-unsaturated fatty acids using fourier transform Raman spectroscopy. AB - The feasibility of Raman spectroscopy in combination with partial least-squares (PLS) regression for the determination of individual or grouped trans monounsaturated fatty acids (trans-MUFA) and conjugated linoleic acids (CLA) in milk fat is demonstrated using spectra obtained at two temperature conditions: room temperature and after freezing at -80 degrees C. The PLS results displayed capability for direct semiroutine quantification of several individual CLA (cis 9,trans-11 and trans-10,cis-12 C18:2) and trans-MUFA (trans-4-15 C18:1) in minor concentrations (below 1.0 g/100 g of milk fat). Calibration models were based on reference data cross-correlation or determined by specific scattering signals in the Raman spectra. Distinct bands for trans-MUFA (1674 cm(-1)) and CLA (1653 cm( 1)) from the trans isolated and cis,trans conjugated C ? C bonds were identified, as well as original evidence for the temperature effect (new bands, peak shifts, and higher intensities) on the Raman spectra of fatty acid methyl ester and triacylglyceride standards, are supplied. PMID- 22084941 TI - SnO2 nanowire logic devices on deformable nonplanar substrates. AB - Logic inverters consisting of n-type FETs and resistors with SnO(2) nanowire channels were fabricated on films of the elastomer polydimethylsiloxane, prestrained and flattened into planar sheets from initial, preformed hemispherical shapes. Upon release, thin and narrow interconnects between individual devices in the arrays absorb induced strain by buckling into nonplanar sinusoidal shapes, to allow full recovery of the surfaces to their original convex geometries. The same physics allows deformation of convex shapes into concave ones, as well as more complex surfaces of coexisting convex and concave areas, and small regions with extremely stretched, locally tapered forms, all nondestructively achieved while maintaining electrical performance, enhanced by use of air gap gate dielectrics. This work shows, more generally, that nanowire devices with both conventional and unusual designs can be integrated into overall systems with irregular, nonplanar layouts, easily deformed in reversible fashion without any measurable alteration in electrical characteristics. The results suggest potential applicability of nanowire technologies in systems of tissue matched implantable electronics for mounting directly on human organs or of sensor skins for integration with robotic manipulators. PMID- 22084942 TI - Ulcerated lupus vulgaris at the site of Bacille Calmette-Guerin vaccination. AB - We report a case of ulcerated lupus vulgaris occurring in 1.5-year-old boy at the Bacille Calmette-Guerin vaccination site within 6 months, which was diagnosed using histology and polymerase chain reaction. The lesion resolved with isoniazid and rifampicin therapy. PMID- 22084943 TI - Recovery, survival, and function of transfused platelets and detection of platelet engraftment after allogeneic stem cell transplantation. AB - BACKGROUND: Recovery and survival of transfused platelets (PLTs) are usually assessed by radioisotope labeling methods for evaluation of transfusion efficacy and new progress in the processing of PLT concentrates. Alternative, nonradioactive methods are warranted. STUDY DESIGN AND METHODS: A multicolor flow cytometry method was developed for simultaneous studies of recovery, survival, and function of transfused PLTs. Eight consecutive patients undergoing allogeneic stem cell transplantation (TX) were transfused with apheresis PLTs of nonself human leukocyte antigen (HLA) Class I types, and HLA Class I discrepancy between donor and recipient was used to identify transfused PLTs. Hematologic status and HLA Class I surface expression were analyzed immediately before transfusion, 1 and 6 hours after transfusion, and daily during the subsequent week. PLT activation was assessed by surface expression of CD63, CD62P, or CD42a, before and after stimulation with thrombin receptor agonist peptide. RESULTS: PLT recovery was 43, 41, and 31% for fresh (5-72 hr old) and 30, 27, and 17% for stored (73-148 hr old) PLTs, after 1, 6, and 15 to 28 hours, respectively. Survival of fresh versus stored PLTs were 160 and 105 hours, respectively. Spontaneous PLT activation and residual activation potential were almost equal for fresh and stored PLTs. PLT engraftment was detected between Day 7 and Day 9, which was significantly earlier than first sign of neutrophil engraftment (Days 11-19; p=0.01). CONCLUSION: Flow cytometry is an attractive alternative to radiolabeling of PLTs for simultaneous studies of survival, recovery, and function of transfused PLTs and early detection of PLT engraftment after allogeneic stem cell TX. PMID- 22084945 TI - Law, marriage and illegitimacy in nineteenth-century Germany. AB - Abstract Concern arose among legislators in several German States during the first half of the nineteenth century about overpopulation and increasing numbers of the impoverished classes. This led them to pass legislation restricting marriage to those considered by the community authorities as morally and financially capable of rearing a family. Census data at the time of the repeal of these laws indicate the extent to which they succeeded in repressing marriage. Declining illegitimacy which paralleled the repeal, however, suggests strongly that the legislation was far less effectual in limiting reproduction than it was in preventing marriage. Added confirmation of this interpretation is provided by the contrasting nuptiality and illegitimacy patterns of German states with liberal marriage regulations. PMID- 22084946 TI - Abortion in amsterdam. AB - Abstract Mortality from abortion is low in the Netherlands to-day, and approximately equal to mortality at delivery. Calculations suggest that about 4,000 abortions occur in Amsterdam every year, of which about 2,100 are induced. The abortion rate shows a very gradual decline after the Second World War. An investigation of the social background of women with induced abortion showed no relationship between occupational group and the incidence of abortion, but a strong negative correlation between religion and abortion. Abortion was more common among women with disturbed relationships in their own or parental families. Induced abortion usually occurred in pregnancies resulting from failure of contraception; these failures were caused not by lack of knowledge of good contraceptives, but by ineffective practice of contraception. The inability to use contraceptive methods in an effective way is related to a lack of communication between the two partners, and to a negative attitude of the women towards sex. An attempt has been made to formulate a theory of the causes of induced abortion among the women interviewed in Amsterdam. PMID- 22084947 TI - Family planning and fecundity. AB - Abstract A computerized probability model of family-building, FERMOD, is described and then utilized in an investigation of relations between family planning and fecundity as applying to white couples of the contemporary United States. Models of this type that formulate reproductive performance as a stochastic process permit one to explore relations that are not directly observable and in this manner to secure at least partial answers to questions not subject to investigation by survey research alone. Two main questions are addressed concerning the dependence of family planning success upon fecundity: (1) How quickly does spacing control deteriorate when natural fecundability is taken at progressively lower values or when the risk of pregnancy wastage is set at progressively higher values? (2) What is the distribution of unsought births among couples of average fecundity when they practise contraception with specified effectiveness and have stipulated spacing and family size goals? PMID- 22084948 TI - Local variations of fertility in taiwan. AB - Abstract Taiwan has attracted a considerable amount of demographic interest in recent years because of a marked decline of fertility since 1956. In this paper the authors utilize data from the household registration system to analyse variations of fertility among 292 local administrative areas in 1961. The study reveals a strong negative correlation between total fertility and a series of indicators of social development and communication. Most of the variation in fertility is accounted for by differences in the fertility of married women aged over 30 and in the age at marriage. The decline of total fertility is accounted for primarily by a reduction of the marital fertility of women over 30. The adoption of family limitation was by no means confined to urban centres, but apparently originated there and spread rapidly to small towns and rural areas. PMID- 22084949 TI - The malthusian theory in pre-civil War America. AB - Abstract Malthusian pessimism was singled out as the most vulnerable expression of the dominant, classical school of economics. Boston idealists, who saw the Malthusian concept as 'a curb to all reform', searched for a rebuttal in the study of institutional economics. The Pennsylvania protectionists, centred about Henry C. Carey, attacked the Malthusian concept as a barrier to the proposed 'American system' which was designed to increase population densities by promoting industrial growth. The fusion of these two schools of thought with the Free Soil elements in the Republican party brought about what many at the time considered a decisive defeat of the Malthusian philosophy in America. Clearly this was not so, for Malthus was never more popular than in post-Civil War America. Why this was so is the subject of this paper. There are various possibilities: The growing influence of Spencer, Mill and Darwin was certainly a factor, and four years of civil bloodshed appear to have reconciled many to the tragic view of life found in the Malthusian concept. Also, the wagefund doctrine was widely accepted during this period of industrial growth. Whatever the reasons, Malthus again proved his curious vitality after being buried by his enemies. PMID- 22084950 TI - Obituary: sir alexander carr-saunders. PMID- 22084953 TI - Prognostic significance of matrix metalloproteinase-2, -8, -9, and -13 in oral tongue cancer. AB - BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. Mechanisms of this disease progression are not fully known. We aimed at finding new predictive markers for diagnosis and disease monitoring. METHODS: Seventy-three consecutive T1N0M0 and T2N0M0 OTSCC patients treated at Helsinki University Central Hospital, Helsinki, Finland, in 1992-2002 were included. Tissue array blocks were prepared from primary tumors and immunostained. Immunoexpression of matrix metalloproteinase (MMP)-2, -8, -9, and 13 was compared with patient characteristics and outcome. RESULTS: Nuclear expression of MMP-13, but not cytoplasmic expression of MMP-2, -8, and -9, was associated with invasion depth (P = 0.017) and tumor size (P = 0.008). Furthermore, high nuclear MMP-13 expression was predictive of poor outcome (P = 0.042). CONCLUSION: Our results suggest that especially MMP-13 may be regarded as a prognostic biomarker in OTSCC. PMID- 22084954 TI - Evaluation and use of NS1 IgM antibody detection for acute dengue virus diagnosis: report from an outbreak investigation. AB - The usefulness of detecting circulating non-structural protein 1 (NS1) IgM antibodies for diagnosing acute dengue virus infection was evaluated during an outbreak investigation along with other routinely used laboratory diagnostic methods. For the first time, the samples were also tested for NS1 antigen detection. NS1 IgM antibody detects all the serum samples that were positive for NS1 antigen detection within first 5 days of infection. The sensitivity of the NS1 IgM ELISA was higher when compared with RT-PCR and therefore, it could be used for early diagnosis. PMID- 22084955 TI - HIV risk among drug-using men who have sex with men, men selling sex, and transgender individuals in Vietnam. AB - Knowledge about drug use and its association with HIV risk among men who have sex with men is limited. Although the HIV epidemic among this population in Vietnam is increasingly acknowledged, understanding the impact of drug use on the spread of HIV is largely lacking. Using qualitative data from in-depth interviews and focus group discussions with 93 drug users, 15 non-drug users and 9 community stakeholders, this analysis explores emerging patterns of drug use and risk factors for engaging in risk behaviours among drug-using men having sex with men, men selling sex and transgender individuals in Hanoi and Ho Chi Minh City. Findings revealed that drug use is shifting from heroin to ecstasy and ice. Drug users reported unsafe sex associated with drug use and men selling sex were particularly at elevated risk because of using drugs as a tool for sex work and trading sex for drugs. These findings are guiding development of programmes addressing unmet HIV-prevention needs in Vietnam. PMID- 22084956 TI - Economic burden of Pseudomonas aeruginosa infection in patients with cystic fibrosis. AB - OBJECTIVE: Chronic infection with Pseudomonas aeruginosa (PA) is the primary cause of pulmonary deterioration in cystic fibrosis (CF). This study describes healthcare costs and resource utilization among CF patients following PA infection in the US. METHODS: This retrospective study utilized data from MarketScan claims database. CF patients with an initial PA infection were identified, and their healthcare utilization, medical and pharmacy costs were extracted for 12 months, pre- and post-PA infection. Descriptive and pair-wise non-parametric statistical analyses compared healthcare utilization and costs before and after infection. RESULTS: Three hundred and fifty-eight CF patients met study criteria (mean age 20.1 years; 48% female). Mean annual per-patient costs following initial PA infection increased by an estimated $18,516 (outpatient: $3113; inpatient: $10,123; pharmacy: $4943). Overall healthcare costs were significantly higher (p < 0.0001) following PA infection, as were overall inpatient visits, outpatient visits, and unique prescriptions (p < 0.0001). CONCLUSIONS: PA infection in cystic fibrosis creates a significant economic burden and the cost is not uniformly distributed across the healthcare components. LIMITATIONS: Key limitations of this study include the absence of clinical parameters to characterize PA infections and data on indirect costs such as loss of productivity or caretaker-related burden. PMID- 22084957 TI - Cost-effectiveness analysis of valsartan versus losartan and the effect of switching. AB - OBJECTIVES: Losartan will shortly become generic, and this may encourage switching to the generic drug. However, valsartan was shown in a meta-analysis to be statistically superior in lowering blood pressure (BP) to losartan. This paper examines the costs of treatment with these two drugs and the potential consequences of switching established valsartan patients to generic losartan. METHODS: A US payer cost-effectiveness model was developed incorporating the risk of cardiovascular disease (CVD) events related to systolic blood pressure (SBP) control comparing valsartan to continual losartan and switching from valsartan to generic losartan. The model, based upon a meta-analysis by Nixon et al. and Framingham equations, included first CVD event costs calculated from US administrative data sets and utility values from published sources. The modeled outcomes were number of CVD events, costs and incremental cost per quality adjusted life-year (QALY) and life-year (LY). RESULTS: Fewer patients had fatal and non-fatal CVD events with valsartan therapy compared with continual losartan and with patients switched from valsartan to generic losartan. The base-case model results indicated that continued treatment with valsartan had an incremental cost-effectiveness ratio of $27,268 and $25,460 per life year gained, and $32,313 and $30,170 per QALY gained, relative to continual losartan and switching treatments, respectively. Sensitivity analyses found that patient discontinuation post-switching was a sensitive parameter. Including efficacy offsets with lowered adherence or discontinuation resulted in more favorable ratios for valsartan compared to switching therapy. LIMITATIONS: The model does not evaluate post-primary CVD events and considers change in SBP from baseline level as the sole predictor of CVD risk. CONCLUSIONS: Valsartan appears to be cost-effective compared to switching to generic losartan and switching to the generic drug does not support a cost offset argument over the longer term. Physicians should continue to consider the needs of individual patient and not cost offsets. PMID- 22084958 TI - A framework for image-based classification of mitotic cells in asynchronous populations. AB - High content screening (HCS) has emerged an important tool for drug discovery because it combines rich readouts of cellular responses in a single experiment. Inclusion of cell cycle analysis into HCS is essential to identify clinically suitable anticancer drugs that disrupt the aberrant mitotic activity of cells. One challenge for integration of cell cycle analysis into HCS is that cells must be chemically synchronized to specific phases, adding experimental complexity to high content screens. To address this issue, we have developed a rules-based method that utilizes mitotic phosphoprotein monoclonal 2 (MPM-2) marker and works consistently in different experimental conditions and in asynchronous populations. Further, the performance of the rules-based method is comparable to established machine learning approaches for classifying cell cycle data, indicating the robustness of the features we use in the framework. As such, we suggest the use of MPM-2 analysis and its associated expressive features for integration into HCS approaches. PMID- 22084959 TI - Transitions experienced by older survivors of critical care. AB - The transition from hospital to home is complicated for older adults who experience a serious or life-threatening illness. The specific aims of this prospective, observational cohort study were to determine the number of older adults who experience a change in their functional ability and residence after an intensive care unit (ICU) stay and to explore risk factors for functional decline and new institutionalization at hospital discharge. We found high rates of unrecognized preexisting cognitive impairment, delirium, complications, functional decline, and new institutionalization in this sample (N = 43). A number of variables were associated with functional decline or new institutionalization, including narcotic agent use (p = 0.03), ICU complications (p = 0.05), comorbidities (p = 0.01), depression (p = 0.05), and severity of illness (p = 0.05). We identified device self-removal, admission type, and ICU delirium as also potentially associated with these outcomes (p <= 0.25). There are a number of important and potentially modifiable factors that influence an older adult's ability to recover after a critical illness. PMID- 22084960 TI - Initial efficacy of a cardiac rehabilitation transition program: Cardiac TRUST. AB - The purpose of this pilot study was to test the initial efficacy, feasibility, and safety of a specially designed postacute care transitional rehabilitation intervention for cardiac patients. Cardiac Transitional Rehabilitation Using Self Management Techniques (Cardiac TRUST) is a family-focused intervention that includes progressive low-intensity walking and education in self-management skills to facilitate recovery following a cardiac event. Using a randomized two group design, exercise self-efficacy, steps walked, and participation in an outpatient cardiac rehabilitation (CR) program were compared in a sample of 38 older adults (17 Cardiac TRUST, 21 usual care). At discharge from postacute care, the intervention group trended toward higher levels of self-efficacy for exercise outcomes than the usual care group. During the 6 weeks following discharge, the intervention group had greater attendance in outpatient CR and a trend toward more steps walked during the first week. The feasibility of the intervention was better for the home health care participants than for those in the skilled nursing facility. The provision of CR during postacute care has the potential to bridge the gap in transitional services from hospitalization to outpatient CR for these patients at high risk for future cardiac events. Further evidence of the efficacy of Cardiac TRUST is warranted. PMID- 22084961 TI - Medication regimens in older home care patients. AB - Medication regimens in older patients have been strongly associated with adverse events leading to hospitalization in ambulatory care settings. Despite a 29% hospitalization rate, to date, no research regarding medication regimens and readmission to the hospital has been completed in the home care setting. As part of a larger study evaluating predictors of readmission to the hospital from home care, descriptive analyses, chi-square tests, and t tests for independent samples were used in this secondary analysis to evaluate the Outcome and Assessment Information Set and medication records from 911 older patients admitted from the hospital to 15 home care agencies. Patients readmitted back to the hospital were older, sicker, and more cognitively impaired, and had complex medication regimens that included significant polypharmacy and inappropriate medication use. Nurses working with older adults need to be especially vigilant in monitoring medication regimens of patients to reduce opportunities for adverse drug events and subsequent hospitalization. PMID- 22084962 TI - Chronic grief management for dementia caregivers in transition: intervention development and implementation. AB - Research reveals that Alzheimer's disease (AD) caregivers do not relinquish their role after placing a family member in long-term care. Caregivers report increased emotional upset around the time of placement, with sustained losses over time leading to chronic grief. Chronic grief increases caregivers' risk for depression and suicide. There are no documented interventions designed to decrease caregivers' chronic grief post placement. The Chronic Grief Management Intervention (CGMI) builds on existing evidence to target caregivers' chronic grief in the transition of a family member into long-term care. The intervention is structured into three major components: (a) knowledge, (b) communication and conflict resolution skills, and (c) chronic grief management skills. The 12-week intervention was pilot tested with 34 caregivers for feasibility and preliminary effects on caregiver skill, knowledge, chronic grief, and depression. This article presents a general study description while focusing on the development and implementation of the CGMI. PMID- 22084963 TI - Medication reconciliation in nursing homes: thematic differences between RN and LPN staff. AB - The purpose of this qualitative descriptive study was to describe medication reconciliation practices in nursing homes with a specific focus on nursing staff involvement in the process. The study was conducted in eight Midwestern nursing homes and included 46 onsite observations of resident transfers to the nursing home. Informal interviews of nursing staff performing medication reconciliation were conducted during each observation. Findings suggest nursing home nursing staff, including both RN and licensed practical nurse (LPN) staff, were primarily responsible for performing medication reconciliation; however, these staff often varied in how they processed resident transfer information to identify medication order discrepancies. Patterns of differences were found related to their perceptions about medication reconciliation, as well as their actions when performing the process. RN staff were more often focused on resident safety and putting the "big picture" together, whereas LPN staff were more often focused on the administrative assignment and "completing the task." PMID- 22084964 TI - Substance abuse in older adults: policy issues. AB - By 2020, it is projected that the number of older adults needing treatment for drug and alcohol addictions will increase dramatically. Although Medicare covers treatment for mental health issues, copayments can be prohibitive for those with lower incomes. The Positive Aging Act, an amendment to the Public Health Service Act, is a policy alternative that could address substance abuse in the older adult population by (a) demonstrating ways of integrating mental health services for older adults into primary care settings, and (b) supporting the establishment and maintenance of interdisciplinary geriatric mental health outreach teams in community settings where older adults reside or receive social services. Increasing funding to states to emphasize primary care provider education on the detection, evaluation, and treatment of substance abuse problems of older adults has the potential to better meet the substance abuse needs of this population. Educating primary care providers, including gerontological nurses, to recognize signs of substance abuse in this population and providing age-appropriate treatment options is critically important but will require funding beyond what is currently available. PMID- 22084965 TI - Aging and living with HIV/AIDS. AB - With individuals either living longer with the disease or contracting it at a later stage in life, HIV/AIDS can no longer be regarded as just a young person's disease. In fact, people older than 50 will represent 50% of HIV/AIDS cases by 2015. The intersection of aging and HIV/AIDS is explored in this article through the use of an individual example highlighting typical age-related issues encountered in living with a chronic HIV infection and two of the more common comorbid conditions. Nursing implications for managing these conditions depression and dyslipidemia-as well as other considerations for providing care to older adults with HIV/AIDS are addressed. PMID- 22084966 TI - Biochemical investigation of the formation of three-dimensional networks from DNA grafted large silica particles. AB - DNA is used to rationally build up networks of silica nanoparticles (SiNPs) based on the molecular recognition properties of complementary sequences. Network self assembly is controlled from DNA covalently grafted at the surface of chemically modified SiNPs. Two strategies are compared, where grafted DNA sequences are designed in a three-strand system using noncomplementary sequences and an extra DNA linker, or in a two-strand approach for direct hybridization. In this paper, both systems are compared in terms of DNA hybridization stability, network size, and three-dimensional organization using a combination of dynamic light scattering and electron microscopy. The observed differences are discussed in terms of hybridization interactions between DNA sequences in particle-free systems through fluorescence, circular dichroism, and UV spectroscopy techniques. PMID- 22084967 TI - Would vaccination against nicotine be a cost-effective way to prevent smoking uptake in adolescents? AB - AIMS: We used epidemiological modelling to assess whether nicotine vaccines would be a cost-effective way of preventing smoking uptake in adolescents. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We built an epidemiological model using Australian data on age-specific smoking prevalence; smoking cessation and relapse rates; life-time sex-specific disability-adjusted life years lived for cohorts of 100,000 smokers and non-smokers; government data on the costs of delivering a vaccination programme by general practitioners; and a range of plausible and optimistic estimates of vaccine cost, efficacy and immune response rates based on clinical trial results. We first estimated the smoking uptake rates for Australians aged 12-19 years. We then used these estimates to predict the expected smoking prevalence in a birth cohort aged 12 in 2003 by age 20 under (i) current policy and (ii) different vaccination scenarios that varied in cost, initial vaccination uptake, yearly re-vaccination rates, efficacy and a favourable vaccine immune response rate. FINDINGS: Under the most optimistic assumptions, the cost to avert a smoker at age 20 was $44,431 [95% confidence interval (CI) $40,023-49,250]. This increased to $296,019 (95% CI $252,307 $355,930) under more plausible scenarios. The vaccine programme was not cost effective under any scenario. CONCLUSIONS: A preventive nicotine vaccination programme is unlikely to be cost-effective. The total cost of a universal vaccination programme would be high and its impact on population smoking prevalence negligible. For these reasons, such a programme is unlikely to be publicly funded in Australia or any other developed country. PMID- 22084968 TI - Non-covalent monolayer-piercing anchoring of lipophilic nucleic acids: preparation, characterization, and sensing applications. AB - Functional interfaces of biomolecules and inorganic substrates like semiconductor materials are of utmost importance for the development of highly sensitive biosensors and microarray technology. However, there is still a lot of room for improving the techniques for immobilization of biomolecules, in particular nucleic acids and proteins. Conventional anchoring strategies rely on attaching biomacromolecules via complementary functional groups, appropriate bifunctional linker molecules, or non-covalent immobilization via electrostatic interactions. In this work, we demonstrate a facile, new, and general method for the reversible non-covalent attachment of amphiphilic DNA probes containing hydrophobic units attached to the nucleobases (lipid-DNA) onto SAM-modified gold electrodes, silicon semiconductor surfaces, and glass substrates. We show the anchoring of well-defined amounts of lipid-DNA onto the surface by insertion of their lipid tails into the hydrophobic monolayer structure. The surface coverage of DNA molecules can be conveniently controlled by modulating the initial concentration and incubation time. Further control over the DNA layer is afforded by the additional external stimulus of temperature. Heating the DNA-modified surfaces at temperatures >80 degrees C leads to the release of the lipid-DNA structures from the surface without harming the integrity of the hydrophobic SAMs. These supramolecular DNA layers can be further tuned by anchoring onto a mixed SAM containing hydrophobic molecules of different lengths, rather than a homogeneous SAM. Immobilization of lipid-DNA on such SAMs has revealed that the surface density of DNA probes is highly dependent on the composition of the surface layer and the structure of the lipid-DNA. The formation of the lipid-DNA sensing layers was monitored and characterized by numerous techniques including X-ray photoelectron spectroscopy, quartz crystal microbalance, ellipsometry, contact angle measurements, atomic force microscopy, and confocal fluorescence imaging. Finally, this new DNA modification strategy was applied for the sensing of target DNAs using silicon-nanowire field-effect transistor device arrays, showing a high degree of specificity toward the complementary DNA target, as well as single-base mismatch selectivity. PMID- 22084969 TI - New developments for the sensitivity estimation in four-way calibration with the quadrilinear parallel factor model. AB - Appropriate closed-form expressions are known for estimating analyte sensitivities when calibrating with one-, two-, and three-way data (vectors, matrices, and three-dimensional arrays, respectively, built with data for a group of samples). In this report, sensitivities are estimated for calibration with four-way data using the quadrilinear parallel factor (PARAFAC) model, making it possible to assess important figures of merit for method comparison or optimization. The strategy is based on the computation of the uncertainty in the fitted PARAFAC parameters through the Jacobian matrix. Extensive Monte Carlo noise addition simulations in four-way data systems having widely different overlapping situations are helpful in supporting the present approach, which was also applied to two experimental analytical systems. With this proposal, the estimation of the PARAFAC sensitivity for calibration scenarios involving three- and four-way data may be considered complete. PMID- 22084970 TI - Analysis of very elderly (>=80 years) non-hodgkin lymphoma: impact of functional status and co-morbidities on outcome. AB - Data on outcome, prognostic factors, and treatment for very elderly non-Hodgkin lymphomas (NHL) is sparse. We conducted a multicentre retrospective analysis of NHL patients >=80 years (at diagnosis) treated between 1999 and 2009. Detailed characteristics were obtained including geriatric syndromes, activities of daily living (ADLs), and co-morbidities using the Cumulative Illness Rating Scale Geriatrics (CIRS-G). We identified 303 patients: 170 aggressive NHL (84% B cell/16% T cell) and 133 indolent NHL (82% B cell/18% T cell). Median age was 84 years (80-95). A geriatric syndrome was present in 26% of patients, 18% had >=1 grade 4 CIRS-G, and 14% had loss of ADLs. At 49-month median follow-up, 4-year progression-free (PFS) and overall survival (OS) for aggressive NHLs were 31% and 44% respectively (stage I/II: PFS 53% and OS 66%; stage III/IV: PFS 20% and OS 32%; P < 0.0001 and 0.0002, respectively). Four-year PFS and OS for indolent NHL were 44% and 66% respectively, regardless of stage. Multivariate regression analysis identified two key factors that predicted inferior PFS and OS for both NHL groups: lack of CR and loss of ADLs. Prospective studies for very elderly NHL that incorporate geriatric tools, especially ADLs, are warranted. PMID- 22084971 TI - Modeling spatial variations of black carbon particles in an urban highway building environment. AB - Highway-building environments are prevalent in metropolitan areas. This paper presents our findings in investigating pollutant transport in a highway-building environment by combing field measurement and numerical simulations. We employ and improve the Comprehensive Turbulent Aerosol Dynamics and Gas Chemistry (CTAG) model to simulate the spatial variations of black carbon (BC) concentrations near highway I-87 and an urban school in the South Bronx, New York. The results of CTAG simulations are evaluated against and agree adequately with the measurements of wind speed, wind directions, and BC concentrations. Our analysis suggests that the BC concentration at the measurement point of the urban school could decrease by 43-54% if roadside buildings were absent. Furthermore, we characterize two generalized conditions in a highway-building environment, i.e., highway-building canyon and highway viaduct-building. The former refers to the canyon between solid highway embankment and roadside buildings, where the spatial profiles of BC depend on the equivalent canyon aspect ratio and flow recirculation. The latter refers to the area between a highway viaduct (i.e., elevated highway with open space underneath) and roadside buildings, where strong flow recirculation is absent and the spatial profiles of BC are determined by the relative heights of the highway and buildings. The two configurations may occur at different locations or in the same location with different wind directions when highway geometry is complex. Our study demonstrates the importance of incorporating highway-building interaction into the assessment of human exposure to near-road air pollution. It also calls for active roles of building and highway designs in mitigating near-road exposure of urban population. PMID- 22084972 TI - Perceived burden in adherence of antiretroviral treatment in rural China. AB - To determine the level of antiretroviral treatment adherence and explore the correlated factors of perceived burden of taking antiretroviral medications among people living with HIV (PLH) in a rural area of China. Data were collected from 66 PLH who were currently receiving antiretroviral treatment. Face-to-face interviews were conducted during August to October, 2009. Approximately 18.2% of participants failed to adhere to antiretroviral treatment in the previous 30 days. A majority of PLH reported that taking antiretroviral medications posed a burden to them. Those who perceived a higher level of burden were more likely to be women, to have lower annual income, and to report a high level of depressive symptoms, poor physical health, and strained family interactions. Findings suggest that future programs in promoting adherence to antiretroviral treatment should address issues related to psychosocial well-being and PLH's interactions with their family members. PMID- 22084973 TI - DNA strand cleavage by the phenazine di-N-oxide natural product myxin under both aerobic and anaerobic conditions. AB - Heterocyclic N-oxides are an interesting class of antitumor agents that selectively kill the hypoxic cells found in solid tumors. The hypoxia-selective activity of the lead compound in this class, tirapazamine, stems from its ability to undergo intracellular one-electron reduction to an oxygen-sensitive drug radical intermediate. In the presence of molecular oxygen, the radical intermediate is back-oxidized to the parent molecule. Under hypoxic conditions, the extended lifetime of the drug radical intermediate enables its conversion to a highly cytotoxic DNA-damaging intermediate via a "deoxygenative" mechanism involving the loss of oxygen from one of its N-oxide groups. The natural product myxin is a phenazine di-N-oxide that displays potent antibiotic activity against a variety of organisms under aerobic conditions. In light of the current view of heterocyclic N-oxides as agents that selectively operate under hypoxic conditions, it is striking that myxin was identified from Sorangium extracts based upon its antibiotic properties under aerobic conditions. Therefore, we set out to examine the molecular mechanisms underlying the biological activity of myxin. We find that myxin causes bioreductively activated, radical-mediated DNA strand cleavage under both aerobic and anaerobic conditions. Our evidence indicates that strand cleavage occurs via a deoxygenative metabolism. We show that myxin displays potent cytotoxicity against the human colorectal cancer cell line HCT-116 under both aerobic and anaerobic conditions that is comparable to the cell-killing properties of tirapazamine under anaerobic conditions. This work sheds light on the processes by which the naturally occurring aromatic N-oxide myxin gains its potent antibiotic properties under aerobic conditions. Furthermore, these studies highlight the general potential for aromatic N-oxides to undergo highly cytotoxic deoxygenative metabolism following enzymatic one electron reduction under aerobic conditions. PMID- 22084974 TI - Progressive strength training (10 RM) commenced immediately after fast-track total knee arthroplasty: is it feasible? AB - PURPOSE: To explore the feasibility of progressive strength training commenced immediately after total knee arthroplasty (TKA). METHODS: A pilot study was conducted at an outpatient training facility. Fourteen patients with unilateral TKA were included from a fast-track orthopedic arthroplasty unit. They received rehabilitation including progressive strength training of the operated leg (leg press and knee-extension), using relative loads of 10 repetition maximum with three training sessions per week for 2 weeks. Rehabilitation was commenced 1 or 2 days after TKA. At each training session, knee pain, knee joint effusion and training load were recorded. Isometric knee-extension strength and maximal walking speed were measured before the first and last session. RESULTS: The training load increased progressively (p < 0.0001). Patients experienced only moderate knee pain during the strength training exercises, but knee pain at rest and knee joint effusion (p < 0.0001) were unchanged or decreased over the six training sessions. Isometric knee-extension strength and maximal walking speed increased by 147 and 112%, respectively. CONCLUSION: Progressive strength training initiated immediately after TKA seems feasible, and increases knee extension strength and functional performance without increasing knee joint effusion or knee pain. PMID- 22084975 TI - ZraP is a periplasmic molecular chaperone and a repressor of the zinc-responsive two-component regulator ZraSR. AB - The bacterial envelope is the interface with the surrounding environment and is consequently subjected to a barrage of noxious agents including a range of compounds with antimicrobial activity. The ESR (envelope stress response) pathways of enteric bacteria are critical for maintenance of the envelope against these antimicrobial agents. In the present study, we demonstrate that the periplasmic protein ZraP contributes to envelope homoeostasis and assign both chaperone and regulatory function to ZraP from Salmonella Typhimurium. The ZraP chaperone mechanism is catalytic and independent of ATP; the chaperone activity is dependent on the presence of zinc, which is shown to be responsible for the stabilization of an oligomeric ZraP complex. Furthermore, ZraP can act to repress the two-component regulatory system ZraSR, which itself is responsive to zinc concentrations. Through structural homology, ZraP is a member of the bacterial CpxP family of periplasmic proteins, which also consists of CpxP and Spy. We demonstrate environmental co-expression of the CpxP family and identify an important role for these proteins in Salmonella's defence against the cationic antimicrobial peptide polymyxin B. PMID- 22084978 TI - Total synthesis of (+/-)-maistemonine, (+/-)-stemonamide, and (+/-) isomaistemonine. AB - A full account of the total synthesis of (+/-)-maistemonine, (+/-)-stemonamide, and (+/-)-isomaistemonine is presented. Two approaches have been developed to construct the basic pyrrolo[1,2-a]azepine core of the Stemona alkaloids, featuring a tandem semipinacol/Schmidt rearrangement of a secondary azide and a highly stereoselectively desymmetrizing intramolecular Schmidt reaction, respectively. To build the common spiro-gamma-butyrolactone, a new protocol was carried out by utilizing an intramolecular ketone-ester condensation as the key transformation. The vicinal butyrolactone moiety of (+/-)-maistemonine was stereoselectively introduced via a one-pot procedure involving the epimerization at C-3 and carbonyl allylation/lactonization. Moreover, (+/-)-stemonamide was divergently synthesized from a common intermediate, and (+/-)-isomaistemonine was obtained via the epimerization of (+/-)-maistemonine at C-12. PMID- 22084976 TI - The hierarchical factor model of ADHD: invariant across age and national groupings? AB - OBJECTIVE: To examine the factor structure of attention-deficit/hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and sibling samples, across three different instruments and across parent and teacher informants. Specific consideration was given to factorial invariance analyses across different ages and different countries in the ADHD sample. METHOD: A sample of children and adolescents between 5 and 17 years of age with ADHD and their unselected siblings was assessed. Participants were recruited from seven European countries and Israel. ADHD symptom data came from a clinical interview with parents Parental Account of Childhood Symptoms and questionnaires from parents and teachers (Conners Parent and Teacher). RESULTS: A hierarchical general factor model with two specific factors best represented the structure of ADHD in both the ADHD and unselected sibling groups, and across informants and instruments. The model was robust and invariant with regard to age differences in the ADHD sample. The model was not strongly invariant across different national groups in the ADHD sample, likely reflecting severity differences across the different centers and not any substantial difference in the clinical presentation of ADHD. CONCLUSIONS: The results replicate previous studies of a model with a unitary ADHD component and separable specific traits of inattention and hyperactivity/impulsivity. The unique contribution of this study was finding support for this model across a large developmental and multinational/multicultural sample and its invariance across ages. PMID- 22084979 TI - Investigation of different apple cultivars by high resolution magic angle spinning NMR. A feasibility study. AB - (1)H HR-MAS NMR spectroscopy was applied to apple tissue samples deriving from 3 different cultivars. The NMR data were statistically evaluated by analysis of variance (ANOVA), principal component analysis (PCA), and partial least-squares discriminant analysis (PLS-DA). The intra-apple variability of the compounds was found to be significantly lower than the inter-apple variability within one cultivar. A clear separation of the three different apple cultivars could be obtained by multivariate analysis. Direct comparison of the NMR spectra obtained from apple tissue (with HR-MAS) and juice (with liquid-state HR NMR) showed distinct differences in some metabolites, which are probably due to changes induced by juice preparation. This preliminary study demonstrates the feasibility of (1)H HR-MAS NMR in combination with multivariate analysis as a tool for future chemometric studies applied to intact fruit tissues, e.g. for investigating compositional changes due to physiological disorders, specific growth or storage conditions. PMID- 22084980 TI - Flexible, low-voltage, and low-hysteresis PbSe nanowire field-effect transistors. AB - We report low-hysteresis, ambipolar bottom gold contact, colloidal PbSe nanowire (NW) field-effect transistors (FETs) by chemically modifying the silicon dioxide (SiO(2)) gate dielectric surface to overcome carrier trapping at the NW-gate dielectric interface. While water bound to silanol groups at the SiO(2) surface are believed to give rise to hysteresis in FETs of a wide range of nanoscale materials, we show that dehydration and silanization are insufficient in reducing PbSe NW FET hysteresis. Encapsulating PbSe NW FETs in cured poly(methyl) methacrylate (PMMA), dehydrates and uniquely passivates the SiO(2) surface, to form low-hysteresis FETs. Annealing predominantly p-type ambipolar PbSe NW FETs switches the FET behavior to predominantly n-type ambipolar, both with and without PMMA passivation. Heating the PbSe NW devices desorbs surface bound oxygen, even present in the atmosphere of an inert glovebox. Upon cooling, overtime oxygen readsorption switches the FET polarity to predominantly p-type ambipolar behavior, but PMMA encapsulation maintains low hysteresis. Unfortunately PMMA is sensitive to most solvents and heat treatments and therefore its application for nanostructured material deposition and doping is limited. Seeking a robust, general platform for low-hysteresis FETs we explored a variety of hydroxyl-free substrate surfaces, including silicon nitride, polyimide, and parylene, which show reduced electron trapping, but still large hysteresis. We identified a robust dielectric stack by assembling octadecylphosphonic acid (ODPA) on aluminum oxide (Al(2)O(3)) to form low hysteresis FETs. We further integrated the ODPA/Al(2)O(3) gate dielectric stack on flexible substrates to demonstrate low-hysteresis, low-voltage FETs, and the promise of these nanostructured materials in flexible, electronic circuitry. PMID- 22084981 TI - Febrile ulceronecrotic Mucha-Habermann disease (pityriasis lichenoides et varioliformis acuta fulminans) presenting as Stevens-Johnson syndrome. AB - We present two pediatric patients with pityriasis lichenoides et varioliformis acuta fulminans whose admitting diagnosis was Stevens Johnson Syndrome. The patients were successfully treated with methotrexate and prednisone. These cases highlight the importance of early recognition and treatment of this disease to prevent further morbidity and a potentially fatal prognosis. PMID- 22084982 TI - Non-invasive translational Cynomolgus model for studying folliculogenesis and ovulation using color Doppler ultrasonography. AB - BACKGROUND: In women, different events of folliculogenesis can be measured and evaluated using ultrasound (US) technology. The availability of a non-invasive translational non-human primate model to study these processes would represent a major contribution to further advance R&D efforts toward novel therapies in assisted reproduction. METHODS: In our study, follicular growth and ovulation was measured in six cyclic Cynomolgus monkeys using abdominal Doppler US. RESULTS: The mean follicular diameter on cycle day -6 (cycle day 0=day of ovulation) was 3.7mm that increased to 6.8mm on cycle day -1. After ovulation, the mean diameter decreased to 4.6mm, confirming ovulation. The mean percentage of follicular size reduction after ovulation was 31%. CONCLUSION: Ultrasonography in combination with color-flow Doppler imaging was shown to be a useful, non-invasive translational method to measure ovarian follicular growth and occurrence and timing of follicular rupture in Cynomolgus monkeys. PMID- 22084983 TI - Fertility differentials as evidence of incipient fertility decline in a developing country. AB - Abstract Age data from the 1960 and earlier censuses of Ghana allow the construction of child-woman ratios which appear to indicate the existence of a substantial urban-rural fertility differential. Plausible assumptions of urban rural mortality differentials increase the apparent fertility differential. In this paper recently published data for Statistical Areas in the country's larger towns are used to demonstrate that one explanation for the fertility differential is almost certainly the enumeration of some females in the towns, while one or more of their surviving children were enumerated outside. Nevertheless, in 1960 the four largest towns exhibited birth levels which are likely to have been about 11% below those of the population in the surrounding regions. Roughly half the differential can be attributed to a general urban-rural differential and half to socio-economic differentials within the towns. It is shown that most fertility reduction within the towns may be explained by delayed female marriage, and that such delay is associated with extended education. It is also shown that amongst the higher socio-economic status groups a small part of the reduction can probably be attributed to the prevention of pregnancy within marriage, and that the making of such attempts is positively associated with extended education, urban birth, participation in first and monogamous marriages, Protestantism, and the holding of views about the harmful effect of high population growth rates on attempts to raise living standards. It is argued that these fertility differentials are evidence of some fertility decline among key groups in the population and that such declines are likely to become more widespread. PMID- 22084984 TI - Frequency and timing of intercourse: Its relation to the probability of conception. AB - Abstract This paper describes a simple study of the chance of conception assuming a fixed-length menstrual cycle, a specific probability distribution for the day of ovulation, and a broad and a narrow fertile period. Eight different patterns of intercourse throughout the cycle are considered with frequency of intercourse ranging between 5 and 12 times per cycle. Results are given in terms of chance of conception and in terms of waiting times until conception. PMID- 22084985 TI - Reconstruction of fertility trends for the female population of the U.S.S.R. AB - Abstract The article describes fertility trends among Soviet women during the past 40 years as compared to American women during the same period of time. Period-specific fertility rates were arrived at by relating the annual total of live births to a pattern of age-specific fertility rates estimated for each year and also to the number of women for each single year of age. These rates were then appropriately re-arranged and compressed into five-year age groups to form a series of cohort-specific fertility rates. The findings rest on somewhat conjectural estimates of live births and numbers of women in the U.S.S.R., some of which were originally prepared before the 1959 Soviet census. The tentative evidence shows that changes in the period-specific fertility of Soviet women were far more irregular and dramatic in the past, than among American women. After World War II these rates dropped in the U.S.S.R. below those of the United States, except for women over 30 years of age. On the other hand, the cohort specific rates of Soviet women, although declining from one cohort to the next, at present show their magnitude in the cumulative series for older ages to be marked by higher than among American women. This experimental investigation of fertility in the Soviet Union makes no claim to high standards of accuracy and validity. Its intended purpose is to stress the desirability of shifting emphasis from the temporal and prognostic type of study, characteristic of present-day demographic research about the U.S.S.R., to the generational and historical approach. PMID- 22084986 TI - Life and death in the sixteenth century in the City of York. AB - Abstract Birth data obtained from the parish records of the City of York show a markedly bi-modal seasonal distribution in the sixteenth century. It appeared interesting to compare the expectation of life of individuals born during this period, during the two minimal and two maximal seasons, to determine if there was any adaptive significance in the annual variation of birth rate. No such effect could be established by this study. However, certain conclusions of considerable interest can be drawn. The survivorship functions for either sex, grouped by birth season or on the whole group, are of a rectilinear diagonal type more reminiscent of an avian population rather than man. However the York data were treated, no statistically significant difference appeared between the sexes when their expectation of life was compared, and the female death rate at all times until the end of life was somewhat higher than the male. It appeared that sixteenth-century York tended to care better for their sons than for their daughters, which also appears to be the case in some modern societies of low to moderate living standard. PMID- 22084987 TI - A probability model applicable to the study of inter-live birth intervals and random segments of the same. AB - Abstract This paper deals with an analytical study of two types of birth intervals, viz. 'closed intervals' and 'open intervals' through the application of simple probability theory. The 'closed interval' stands for the time interval between two successive live births of a woman, and the 'open interval' denotes the interval between the date of last live birth and the date of survey for a married woman in the reproductive age group surveyed at a point of time. The study considers the 'closed interval' as the sum of independent random variables, each representing a particular component like post-partum amenorrhea, waiting time in the susceptible state, etc. Approximations to the patterns of distributions of these component random variables are made from the available data collected in fertility surveys at Gandhigram. The 'open interval' for any parity is studied separately for two different (mutually exclusive) categories of women, viz. those who have at least one more live birth at some time or other during their reproductive period and those who cease childbearing. In the first case the 'open interval' is considered as a random segment or partition of the corresponding 'closed interval'; in the second as a random segment of the interval between the date of birth of the last child and date at which the woman attains 45 years of age. The mean and variance of the 'open interval' is obtained separately in each case, and the moments of the 'open interval' distribution for women chosen at random from the population are obtained as an appropriate mixture of the two types. PMID- 22084988 TI - Fertility differences in Andean countries: A reply to W. H. James. AB - Abstract The lower fertility of the Indian-speaking parts of Bolivia, Ecuador and Peru compared with the Spanish-speaking parts of these nations has been the topic of several previous articles in this journal. In last year's journal William H. James argued that higher altitude was the chief cause of this reduced fertility level, whereas D. M. Heer has earlier argued that it might be accounted for by higher proportions of women in the labour force. James's data and Heer's further computations suggest that James's explanation has substantially more merit than that originally advanced by Heer. PMID- 22084991 TI - In vitro and in vivo reduced fitness and virulence in ciprofloxacin-resistant Acinetobacter baumannii. AB - Limited data on relative fitness and virulence of antimicrobial-resistant Acinetobacter baumannii are known. We aimed to study the virulence and fitness cost of ciprofloxacin-resistance in A. baumannii (CipR) compared with the susceptible parental wild-type strain (CipS). Human lung epithelial cells were infected with CipS and CipR for 24 h. Competition fitness was monitored in vitro and in vivo in a murine peritoneal sepsis model. We showed that CipR induced less cell death than CipS and CipR growth was slow when in competition with CipS. Altogether, acquisition of ciprofloxacin resistance confers a biological fitness cost and reduces virulence in A. baumannii. PMID- 22084992 TI - Occupational stigma as a primary barrier to health care for street-based sex workers in Canada. AB - Individuals working in the sex industry continue to experience many negative health outcomes. As such, disentangling the factors shaping poor health access remains a critical public health priority. Within a quasi-criminalised prostitution environment, this study aimed to evaluate the prevalence of occupational stigma associated with sex work and its relationship to barriers to accessing health services. Analyses draw on baseline questionnaire data from a community-based cohort of women in street-based sex work in Vancouver, Canada (2006-2008). Of a total of 252 women, 141 (55.9%) reported occupational sex work stigma (defined as hiding occupational sex work status from family, friends and/or home community), while 125 (49.6%) reported barriers to accessing health services in the previous six months. In multivariable analysis, adjusting for sociodemographic, interpersonal and work environment risks, occupational sex work stigma remained independently associated with an elevated likelihood of experiencing barriers to health access. Study findings indicate the critical need for policy and societal shifts in views of sex work as a legitimate occupation, combined with improved access to innovative, accessible and non-judgmental health care delivery models for street-based sex workers that include the direct involvement of sex workers in development and implementation. PMID- 22084993 TI - The way forward for the clinical teacher. PMID- 22084994 TI - Hospital simulated patient programme: a guide. AB - CONTEXT: Many university courses employ simulated patients to work with students in the development of communication skills. Our challenge was to build a sustainable programme that could be adapted for medical, nursing and allied health staff, and groups of students, on our hospital campus. INNOVATION: In recognition of the need to provide practice opportunities for junior medical staff to hone their capacity to communicate effectively with parents, we employed professional actors who are also qualified teachers. Junior doctors have multiple opportunities over their training time to work one-to-one with an actor-tutor in the role of simulated parent. The simulated parents are skilled in helping the trainees reflect on the conversation, and the trainees are given a recording of their sessions for further reflection and feedback from a colleague. This model has been adapted to meet the 'topic' needs and scheduling requirements of other staff and hospital-based student groups. DISCUSSION: In adapting the original medical staff programme, we came to appreciate not only the logistical but also the ethical considerations inherent in a simulated parent/patient programme. Our guide highlights the importance of safeguarding the educational integrity of the design, maintaining the fidelity of the simulations and ensuring the safety of all involved. PMID- 22084995 TI - An introduction to macrosimulation and Hospex. AB - BACKGROUND: The Hospital Exercise (Hospex) is the pre-deployment training programme used by the UK Defence Medical Services. It is one of only a handful of examples of macrosimulation existing worldwide. Hospex is innovative and engaging, and with the ever-growing evidence base supporting the use of simulation as a teaching tool, it is undoubtedly an invaluable resource from which other organisations could learn. CONTEXT: This article aims to: introduce macrosimulation as a learning technique; present Hospex, one example of the ambitious ways in which simulation can be used; and present some of the evidence in support of simulation. INNOVATION: Field hospital training has existed for decades. However 'early variants lacked realistic clinical input and had little relevance to the needs of the deploying field hospital' [Col. K Gill Late (L), Royal Army Medical Corps Volunteer (V); personal communication]. With war in Iraq and Afghanistan, planners recognised the need for a realistic and relevant training model. This was the beginning of Hospex. Hospex in its current form involves the complete and realistic simulation of an entire field hospital, in which staff work through real-life scenarios in real time. IMPLICATIONS: Evidence supporting the value of simulation as a teaching tool is ever growing. It is a transferrable resource that could be adapted to fit many briefs, including civilian health care training programmes. PMID- 22084996 TI - An educational conference in a general hospital. AB - BACKGROUND: Western Sussex Hospitals National Health Service (NHS) Trust comprises the District General Hospitals of Worthing and Chichester. Both hospitals have successful postgraduate medical education centres, providing training for junior doctors and continuing professional development for senior doctors. Until now, there have been limited multi-professional teaching and learning activities available. CONTEXT: The two hospitals have recently merged. The education executive felt that workplace learning had become undervalued since the implementation of Modernising Medical Careers in the UK. The executive wanted to provide a multi-professional conference on Workplace Learning, both to support the merger and to promote the value of workplace and multi-professional learning. INNOVATION: The conference topic covering the 'how' of workplace learning was innovative. Many educational conferences concentrate on the organisation and evaluation of classroom learning, rather than on how learning can be facilitated in the workplace during ordinary working practice. It was also innovative to ensure that the presenters were representative of the multi-professional workforce. The presentations were limited to 8 minutes each to promote high impact short presentations. The talks were recorded for publishing on the trust's intranet and the internet. IMPLICATIONS: A committed team in a district general hospital can provide a high-quality educational conference with wide appeal. Local health care professionals can produce short high-impact presentations. The use of modern information technology and audio-visual systems can make the presentations available to both local and worldwide audiences. PMID- 22084997 TI - Interactive lecturing. AB - BACKGROUND: Lectures can vary from being entirely teacher-centred through to those that value learner-teacher and learner-learner interaction. Advocates of the exclusively didactic (teacher-centred) lecture aim to maximise the amount of lecture time available to their delivery of content, and regard other activities as 'lost' lecture time. Educational research has, however, identified the potential benefit of interactivity that promotes mentally active learning and improved learning outcomes. This article reviews the notion of 'active learning', outlines how active learning is promoted by interactivity and concludes with strategies for including interactivity within lectures. METHOD: Narrative review and discussion. RESULTS: The article begins with a summary of the purposes of lecturing, and the distinctions between mentally active and passive learning. The associations between interactivity, cognitively active learning and improved learning outcomes are considered, and strategies for promoting interactivity and active learning are explored. Three student-student interaction strategies are discussed, and an exemplar of each of these strategies in action is provided. The exemplar addresses the 'lost time' concern of some advocates of the exclusively didactic lecture. DISCUSSION: Interactivity can be readily introduced to lectures without a significant reduction in the amount of time available for didactic lecturing. This paper challenges the view that the inclusion of interactivity equates to a loss of learning time, by showing that students' achievement of learning outcomes is enhanced by planned and structured engagement with others. The paper concludes with an example of how interactivity can be incorporated within the traditional lecture format. PMID- 22084998 TI - Determinants of learning ultrasound-guided axillary brachial plexus blockade. AB - BACKGROUND AND OBJECTIVES: Training in medical procedural skills is currently undergoing important change. We set out to identify those factors, perceived by trainers and trainees, to be important determinants of learning ultrasound-guided axillary brachial plexus blockade (USgABPB). METHODS: We performed a structured, prospective, qualitative analysis of these determinants using a design-based approach. We collected data using focus groups, semi-structured interviews and questionnaires. RESULTS: Based on 113 responses to a detailed questionnaire, the most important determinants of learning USgABPB were access to and frequency of clinical learning opportunities in the presence of an appropriate trainer. Focus groups determined that meaningful learning opportunities required the coexistence of an appropriate patient, trainee, trainer and environment. Trainers and trainees perceived that the consistent provision of such opportunities required a formal structured training programme. CONCLUSIONS: Optimum training in USgABPB requires a formal structured training programme. We propose that these findings can be used to optimise the design of the curriculum, the training programme and assessment on performing the procedure. PMID- 22084999 TI - Death and dignity through fresh eyes. AB - BACKGROUND: Trinity College Dublin remains one of the Medical Schools that uses traditional dissection to teach anatomy, exposing students from the first week of entry to cadavers. This early exposure makes it imperative that issues surrounding death and donor remains are explored early on within the main structure of the curriculum. CONTEXT: The School of Medicine began a programme of Medical Humanities student-selected modules (SSMs) in 2010, and the opportunity to offer a module on medical ethics regarding death and dignity was taken. INNOVATION: A course was devised that touched only lightly on subjects such as palliative care and the concept of a good death. The course focused much more strongly on the reality of death as part of cultural and societal identity and placement. This was facilitated by field trips to settings where discussions regarding death, dying and dignity were commonplace and authentic experiences, rather than classroom discussions based on theoretical circumstances that may not yet have been experienced by the student. IMPLICATIONS: The module ran very well, with students feeling that they had had a chance to think critically about the role of death as an event with significance within society and culture, rather than purely in a medico-legal framework. Options to extend the module to the compulsory element of the course, to be built upon in later years looking at more technical aspects surrounding death, are being explored. PMID- 22085000 TI - Medical weblogs: advocacy for positive cyber role models. AB - BACKGROUND: The development of empathy and of medical professionalism is important in medical education. Research has shown a decline in empathy during medical study. An important factor that may contribute to this decline is the lack of positive role models. Students identify positive and negative role models in the clinical ward and in classrooms. Positive clinical role models, showing good professionalism, will foster the student's professional growth. CONTEXT: Students base both knowledge and opinions on information they find on the internet, such as 'medical weblogs'. These weblogs may be regarded as a new aspect of the 'informal curriculum', even though they might be written by 'negative role models'. In our experience, students frequently require debriefing of the undifferentiated, frequently disrespectful, grotesque or unprofessional approaches they encounter in general, and in this aspect online in particular. INNOVATION: When written by appropriate professionals, medical weblogs can provide a unique opportunity for the medical student to follow the writings of positive role models. Would it be a worthwhile investment if globally distributed medical professionals from different specialties put time and effort into writing weblogs on their daily practice and reflections? These weblogs could be assembled on one international educational website, labelled as 'professionally approved' and made easily accessible. Medical students internationally would have access to the daily practice of medical professionals who are excellent positive role models. They could also be encouraged to discuss issues with them. We hypothesise that witnessing the encounters of these globally distributed doctors, and following their reflections, may add to the growth of empathy and professionalism in students. PMID- 22085001 TI - Foundation Programme doctors as teachers. AB - BACKGROUND: Teaching is a core competency outlined in the Foundation Programme curriculum in the UK. This article reports data from a larger postal questionnaire study asking general practitioner (GP) trainers and GP programme directors in the Yorkshire & Humber Deanery whether Foundation Year 2 (FY2) doctors were undertaking teaching roles during primary care posts. We also aimed to explore their attitudes towards FY2s as teachers. METHODS: A questionnaire was designed asking whether FY2s had been present in the practice, and if so what teaching methods they had undertaken. The responder was then asked how comfortable they would feel with an FY2 doctor undertaking certain teaching roles. Responses were prompted using a nine-point Likert scale. RESULTS: The response rate was 74 per cent (216/291). Of the respondents, 37 per cent (80/216) stated that FY2s had been present in their surgery in the last 12 months; 16 per cent (13/80) went on to say that those FY2 doctors had undertaken teaching roles. Respondents felt more comfortable with FY2s undertaking the teaching of practical skills (median score 6, interquartile range 5-7, on the Likert scale) and giving one-to-one tutorials to medical students (median score 6, interquartile range range 4-7), but were uncomfortable with them clinically supervising medical students (median score 3, interquartile range 2-5) and giving one-to-one tutorials to fellow FY2s (median 4, interquartile range 2-5). DISCUSSION: With reduced hours resulting in a decrease in exposure to teaching experience during hospital rotations, it is important that these doctors are given adequate opportunities during primary care placements to improve skills in this area. PMID- 22085002 TI - Teaching toolkit for medical students. AB - BACKGROUND: From teaching juniors and peers to educating patients, it is imperative for all doctors to have basic core teaching skills. The Junior Association for the Study of Medical Education (JASME) felt that a short course in the fundamentals of teaching would be well received by students. CONTEXT: This article shares the lessons from a one-day teaching course aimed at senior medical students. Qualitative feedback helped decide which aspects of the course were most valued. INTERVENTION: The course was piloted in London. It combined interactive plenary sessions on teaching theory with practical teaching sessions. Each student taught a small group of others a basic clinical skill, and the student teacher then received extensive feedback from their peers and an experienced clinician with a special interest in medical education. There was an opportunity to re-teach part of the skill after having taken the feedback on board. IMPLICATIONS: Students completed questionnaires at the start and end of the day to ascertain their expectations of the course and what they found most useful. Expectations can be grouped into three main areas: students wanted to improve their teaching skills; gain teaching experience; and receive feedback on their teaching. The most valuable part of the course was being able to practise teaching and receive feedback. Keywords used to describe the feedback included 'individual', 'valuable', 'constructive', 'instant' and 'in depth'. By continuing to run similar workshops we hope that we can further encourage the teachers of tomorrow. PMID- 22085003 TI - Maximising responses to quality assurance surveys. AB - BACKGROUND: In the UK all postgraduate trainees complete an annual online quality assurance survey. If the response rate is poor, then this has significant implications for the validity and usefulness of the data collected. In this article we address the issue of survey response rates, with particular reference to quality assurance surveys, although the principles can be applied generally. METHOD: We have employed mostly evidence-based techniques (predominantly from general survey literature rather than published medical education work). We list the techniques that we have employed. These include a five-stage process of repeated and incremental contact with those who do not complete the survey, backed up by personal contact with an influential figure. Stressing the importance of completing the survey, assuring responses are confidential and keeping the invitation email brief are examples of the techniques used. RESULTS: Over a 3-year period we have managed to improve the response rate from 57 per cent to over 80 per cent. DISCUSSION: We note that role models remain the single most important determinant of medical behaviour, and that if they embrace quality assurance, trainees will too. It is important to employ and build upon the existing literature within the survey methodology. By doing this we can enhance the response rate and validity of future quality assurance surveys, thus reinforcing their role as a key tool as we strive to maximise the effectiveness of interventions in postgraduate medical education. PMID- 22085004 TI - Gen Y learners: just how concerned should we be? AB - BACKGROUND: This article is a response to expressions of concern from a range of sources, including reports of curriculum redesign to accommodate the characteristics of Gen Y, claims made in the press and concerns expressed by educators in the health professions. Are these concerns grounded in research and if so how can educators in the health professions respond? METHOD: Narrative review and discussion. RESULTS: Generation Y is defined, and beliefs about its defining characteristics are reviewed. The key role of marketing companies in the creation and perpetuation of generalised views of Gen Y is addressed, and a review of recent research related to members of this generation is presented. The more extreme claims of Gen Y as a unique generation are critiqued and implications for teaching members of this generation are reviewed. General advice is provided in relation to teaching and supervising Gen Y. DISCUSSION: The numerous claims regarding the uniqueness of Gen Y can be found to largely arise from a limited number of poorly designed and implemented studies, often conducted by marketing companies with a vested interest in promoting a belief in the existence of another unique societal subgroup. The limited educational research conducted to date has emphasised the importance of the relational dimension of learner-teacher interaction as a highly valued attribute of quality teaching. PMID- 22085005 TI - Student doctors taking responsibility. AB - BACKGROUND: New guidelines require all undergraduate medical students to undertake at least one period of assistantship where they assume most of the responsibilities of a first-year graduate doctor (FY1 doctor in the UK) under supervision. AIM: To investigate the feasibility of these assistantships. METHOD: All UK schools were sent a questionnaire addressing the supervision required and the main barriers around implementation. RESULTS: Competencies that students already engage in as part of existing clinical placements and a number of 'tacit' competencies (e.g. practice and promote infection control) were regarded by most as suitable. Activities that present a clear clinical risk (e.g. prescribing and writing clinical correspondence) were regarded by most as unsuitable or requiring continuous supervision. Some lower risk but hard to measure activities (e.g. responding in practice to audit) were also regarded as unsuitable by some. A competency was usually considered inappropriate for one of three reasons: (1) current clinical governance and patient safety protocols appeared to bar students undertaking the competency; (2) a competency was not considered to be part of the current FY1 doctors' role; or (3) brief assistantships were considered unlikely to create sufficient opportunity for performing the competency. DISCUSSION: The article presents a number of practical issues in relation to assigning responsibility to student doctors. Respondents indicate that successful assistantships will only be possible if the UK National Health Service trusts review their attitude to balancing short- and long-term risks: assistantships need to be long enough to create genuine responsibility opportunities, and will require investment in supervision beyond the current capacity. PMID- 22085006 TI - Whatever happened to apprenticeship learning? AB - BACKGROUND: I have been a clinical tutor for 10 years in Worthing Hospital, UK. During this time I have seen an increased emphasis on classroom teaching, assessments in controlled situations and simulation, rather than on apprenticeship learning during well-supervised clinical working. CONTEXT: At the educational conference on 'Learning without Leaving the Workplace' hosted by my hospital, I had an opportunity to present my reflections on apprenticeship or situated learning. This article is a summary of that talk. IMPLICATIONS: The relatively new model of 'situated learning' offers an opportunity for academics and clinicians to revitalise the apprenticeship model of learning in, and being stimulated by, the clinical workplace. PMID- 22085007 TI - Reflections on a surgical elective in Tanzania. PMID- 22085008 TI - Subclinical unprofessionalism. PMID- 22085009 TI - Preparing for practice: what really counts? PMID- 22085014 TI - Feedback fatigue. PMID- 22085015 TI - Histopathological features that predict the recurrence of odontogenic keratocysts. AB - BACKGROUND: Odontogenic keratocysts (OKCs) constitute between 1.8% and 21.5% of odontogenic cysts and are associated with higher propensity to recur than other odontogenic cysts following surgical removal. Previous studies have been performed to identify clinico-pathological predictive factors in relation to such behaviour. The relationship between the presence of hyalinisation and recurrence of the OKC has not been explored. METHODS: A total of 110 OKCs were selected, comprising 53 non-recurrent cases, 50 cases known to subsequently recur and seven syndromic cases. Cases were examined blind, and histological assessment of the epithelial lining, connective tissue capsule and cyst lumen was made. Statistical analysis was completed using Pearson Chi-square, Fisher's exact test and logistic regression analysis. RESULTS: Subepithelial hyalinisation of the underlying connective tissue capsule (P = 0.006) was significantly more common in OKC that recurred. Recurring cysts demonstrating hyalinisation were seen in a younger age group (mean = 40.8 years) than the non-recurrent cysts (mean = 56.4 years). In addition, subepithelial splitting (P = 0.015) and the position of mitotic figures (P = 0.033) were more common in recurring cysts. CONCLUSION: In this case series, several differences were found in relation to histological features of recurring and non-recurring OKCs. There are many factors responsible for the high recurrence rate of OKCs, and the presence of subepithelial hyalinisation may be used as an additional histopathological feature to predict a greater tendency for recurrence. PMID- 22085016 TI - NaV 1.8, but not NaV 1.9, is upregulated in the inflamed dental pulp tissue of human primary teeth. AB - AIM: To investigate alterations in Na(V) 1.8 and Na(V) 1.9 expression within inflamed dental pulp tissue of human primary teeth. METHODOLOGY: Dental pulp tissue obtained from both normal and inflamed pulps in primary teeth as well as pulps from normal and inflamed permanent teeth was used. The quantity of Na(V) 1.8 and Na(V) 1.9 expression in the dental pulp tissue was investigated using Western blot analysis. General neuron marker (PGP9.5) was used to quantify for neural density, and an increase in metalloproteinase-9 was used to indicate pulpal inflammation in inflamed teeth. Statistically significant differences for each determined parameter between normal and inflamed teeth of both primary and permanent teeth were tested using the Mann-Whitney rank sum test. RESULTS: There was no significant difference in neural density of normal and inflamed dental pulp tissue, although degrees of inflammation were increased in the inflamed dental pulp of both permanent and primary teeth (P < 0.05). Na(V) 1.8 and Na(V) 1.9 expression in inflamed pulps of permanent teeth increased significantly compared with normal permanent teeth (P < 0.05). However, only Na(V) 1.8 expression was increased significantly in the inflamed dental pulp of primary teeth (P < 0.05). CONCLUSIONS: Na(V) 1.8 alone may be the therapeutic target for treatment of painful pulpitis in primary teeth. PMID- 22085017 TI - Assessment of the ex vivo biomechanical properties of porcine cornea with inflation test for corneal xenotransplantation. AB - OBJECTIVE: This study aims to obtain the biomechanical properties of porcine cornea so as to provide necessary biomechanical experimental basis for pig-to human corneal xenotransplantation. METHODS: Seventeen fresh porcine corneal specimens obtained from pigs aged 4-6 months were examined under inflation conditions to determine the constitutive relationships of the material through dynamic loading conditions (pressure range: 1.47-42.66 mmHg). The forward deflection of porcine anterior corneal apex was measured by the laser displacement sensor. The pressure deformation results were analysed on the basis of shell theory to estimate Young's modulus of the cornea and derive its relationship with intraocular pressure (IOP). RESULTS: The porcine corneas showed a nonlinear corneal forward displacement/IOP and stress/strain relationship with an initial low stiffness stage and a later high stiffness stage. In spite of the nonlinearity between the internal pressure and apex forward deflection, the relationship between the Young's modulus and the IOP was almost linear. CONCLUSIONS: Compared with human corneas, porcine corneas exhibited a similar nonlinear behaviour but lower stiffness values. The biomechanical parameters of porcine cornea obtained from this test could be applied to numerical simulations of refractive surgery procedures and lay a foundation for pig-to-human corneal xenotransplantation. PMID- 22085018 TI - Evaluation and optimization of compound solubilization and delivery methods in a two-tiered ion channel lead optimization triage. AB - Low-volume dispensing of neat dimethyl sulfoxide (DMSO) into plate-based assays conserves compound, assay reagents, and intermediate dilution plate cost and, as we demonstrate here, significantly improves structure-activity relationship resolution. Acoustic dispensing of DMSO solutions into standard volume 384W plates yielded inconsistent results in studies with 2 cell lines because of apparent effects on the integrity of the cell monolayer (increased intracellular Ca++ levels as indicated by elevated basal dye fluorescence after acoustic transfer). PocketTip-mediated transfer was successful at increasing apparent potency on a more consistent basis. Notably, the correlation coefficient among fluorescence imaging plate reader (FLIPR):electrophysiology (EP) across a representative ~125 compound collection was increased ~5* via conversion to a PocketTip direct dispensation, indicating a triage assay more predictive of activity in the decisional patch-clamp assay. Very importantly, the EP benchmarked false-negative rate as measured by compounds with FLIPR EC50 more than the highest concentration tested fell from >11% to 5% assay-wide, and the relative FLIPR:EP rank-order fidelity increased from 55% to 78%. Elimination of the aqueous intermediate step provided additional benefits, including reduced assay cost, decreased cycle time, and reduced wet compound consumption rate. Direct DMSO dispensing has broad applicability to cell-based functional assays of multiple varieties, especially in cases where limit solubility in assay buffer is a recognized impediment to maximizing interassay connectivity. PMID- 22085020 TI - Nanoparticle assemblies as probes for self-assembled monolayer characterization: correlation between surface functionalization and agglomeration behavior. AB - The ordering of dodecyl chains has been investigated in mixed monolayers of phosphonic acid capping agents on the surface of hydrothermally prepared zirconia nanocrystals. Methyl-, phenyl-, pyryl-, and tert-butylphosphonic acids have been used to investigate series with different mixing ratios with dodecylphosphonic acid as the cocapping agent for the mixed monolayer formation. Fourier transform infrared (FTIR) studies revealed that an increasing amount (different for each type) of coadsorbed capping agent reduces the ordering of the dodecyl chains significantly. Small-angle X-ray scattering (SAXS) verified that with increasing amount of cocapping agent the agglomeration of the particles decreases. The strong correlation of the agglomeration behavior with the ordering of the surface bound alkyl chains leads to the conclusion that interparticle bilayers, formed via long alkyl chain packing, are responsible and can be controlled on a molecular level by coadsorbing various molecules. On the basis of this correlation, nanoparticles can be used as probes for self-assembled monolayer investigation by an indirect structural method (SAXS) and correlated with the routine spectroscopical method for the chemical analysis of surface groups (FTIR). PMID- 22085019 TI - A screening assay to identify agents that enhance T-cell recognition of human melanomas. AB - Although a series of melanoma differentiation antigens for immunotherapeutic targeting has been described, heterogeneous expression of antigens such as Melan A/MART-1 and gp100 results from a loss of antigenic expression in many late stage tumors. Antigen loss can represent a means for tumor escape from immune recognition, and a barrier to immunotherapy. However, since antigen-negative tumor phenotypes frequently result from reversible gene regulatory events, antigen enhancement represents a potential therapeutic opportunity. Accordingly, we have developed a cell-based assay to screen for compounds with the ability to enhance T-cell recognition of melanoma cells. This assay is dependent on augmentation of MelanA/MART-1 antigen presentation by a melanoma cell line (MU89). T-cell recognition is detected as interleukin-2 production by a Jurkat T cell transduced to express a T-cell receptor specific for an HLA-A2 restricted epitope of the Melan-A/MART-1 protein. This cellular assay was used to perform a pilot screen by using 480 compounds of known biological activity. From the initial proof-of-principle primary screen, eight compounds were identified as positive hits. A panel of secondary screens, including orthogonal assays, was used to validate the primary hits and eliminate false positives, and also to measure the comparative efficacy of the identified compounds. This cell-based assay, thus, yields consistent results applicable to the screening of larger libraries of compounds that can potentially reveal novel molecules which allow better recognition of treated tumors by T cells. PMID- 22085021 TI - Bisexual behavior among Chinese young migrant men who have sex with men: implications for HIV prevention and intervention. AB - Data from 307 young migrant men who have sex with men (MSM) in Beijing were analyzed to examine bisexual behavior and the associated sociodemographic and behavioral factors among Chinese young migrant MSM. More than one-fourth (27%) of the MSM were also concurrently engaged in sexual behavior with women (MSMW). Among MSMW, 8.4% were infected with HIV, and 10.8% with Syphilis, compared to 4.9% and 23.7%, respectively, among men who have sex with men only (MSM-only). Various HIV-related risk behaviors among MSMW were similar to those of MSM-only, such as unprotected anal sex, multiple sexual partners, involvement in commercial sex, and substance use. Compared with MSM-only, MSMW were less likely to have tested for HIV, to participate in HIV prevention activities, and were less knowledgeable about condom use and HIV/AIDS. MSMW also had a higher rate of unprotected sex with female stable sexual partners than with male stable sexual partners (79.5% vs. 59.5%). Results indicated that MSMW were at a very high risk for both HIV infection and transmission. Intervention efforts are needed to target this subgroup of MSM and promote AIDS knowledge and HIV/STD testing among MSMW, and to reduce HIV transmission through MSM's bisexual behavior. PMID- 22085022 TI - The high dielectric constant of staphylococcal nuclease is encoded in its structural architecture. AB - The pK(a) values of Lys-66, Glu-66, and Asp-66 buried in the interior of the staphylococcal nuclease Delta+PHS variant were reported to be shifted by as much as 5 pK(a) units from their normal values. Reproducing the pK(a) of these buried ionizable residues using continuum electrostatic calculations required the use of a high protein dielectric constant of 10 or higher. The apparent high dielectric constant has been rationalized as a consequence of a local structural reorganization or increased fluctuations in the microenvironment of the mutation site (Chimenti, M. S., et al. J. Mol. Biol. 2011, 405, 361-377). We have calculated the dielectric constant of Delta+PHS and the Lys-66, Asp-66, and Glu 66 mutants from first principles using the Kirkwood-Frohlich equation and discovered that staphylococcal nuclease has a naturally high dielectric constant ranging from 20 to 30. This high dielectric constant does not change significantly with the mutation of residue 66 or with the ionization of the mutated residues. Calculation of the spatial dependence of the dielectric constant for the microenvironment of residue-66 produces a value of about 10, which matches well with the apparent dielectric constant needed to reproduce pK(a) values from continuum electrostatic calculations. Our results suggest an alternative explanation that the high dielectric constant of staphylococcal nuclease is a property resulting from the intrinsic backbone fluctuations originating from its structural architecture. PMID- 22085023 TI - Speculation on the origin of monochloro-nonabromodiphenyl ethers. Letter to the editor regarding comment on "identification of monochloro-nonabromodiphenyl ethers in the air and soil samples from South China". PMID- 22085024 TI - Age and ethnic differences in the onset, persistence and recurrence of alcohol use disorder. AB - AIMS: To estimate ethnic differences in three components of alcohol use disorder and alcohol dependence course (onset, persistence and recurrence) in a developmental framework. DESIGN: Longitudinal data from The National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), collected using face-to-face interviews. SETTING: Civilian non-institutionalized US population aged 18 years and older, with oversampling of Hispanics, blacks and those aged 18 24 years. PARTICIPANTS: Individuals who completed both NESARC assessments, were not life-long abstainers and were either white (n = 17,458), black (n = 4995), US born Hispanic (n = 2810) or Hispanic-born outside the United States (n = 2389). MEASUREMENTS: Alcohol dependence (AD) and alcohol use disorder (AUD; abuse or dependence) onset, persistence and recurrence were examined using the Alcohol Use Disorders and Associated Disabilities Interview Schedule, DSM-IV version. FINDINGS: Among men: relative to whites aged 18-29, AUD onset and persistence were elevated only in US-born Hispanics aged 40 years and older; odds were reduced for all non-US-born Hispanics, older whites, most blacks and US-born Hispanics aged 30-39. For AD, onset risk was elevated for all younger minority men and only reduced among non-US-born aged Hispanics 40 or older. For women: compared to young whites, non-US-born Hispanics were at decreased AUD and AD onset risk; AUD and AD onset and persistence were increased for older blacks and US-born Hispanics. CONCLUSIONS: In the United States, ethnic differences in alcohol disorder transitions (onset, persistence, and recurrence) vary across age, gender and whether a broad (alcohol use disorder) or narrow (alcohol dependence) alcohol definition is used. Evidence of increased risk for some transitions in minority groups suggests that attention should be paid to the course of alcohol use disorders, and that differences in prevalence should not be assumed to reflect differences in specific transitions. PMID- 22085025 TI - Exploration of oxidative stress and inflammatory markers in relation to urinary phthalate metabolites: NHANES 1999-2006. AB - Phthalate exposure has been associated with a wide range of adverse health outcomes in limited epidemiologic studies, and inflammation and oxidative stress have been hypothesized as potential mechanisms involved. In the present study we investigated associations between urinary concentrations of phthalate metabolites and potential blood markers of oxidative stress (bilirubin) and inflammation (alkaline phosphatase [ALP], absolute neutrophil count [ANC], ferritin [adjusted for iron status], and fibrinogen), using data from 10,026 participants in the National Health and Nutrition Examination Survey (NHANES) recruited between 1999 and 2006. After adjustment for covariates we found that bilirubin was inversely associated with several phthalate metabolites (all p-values <0.0001), including the metabolites of di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP), in addition to monobenzyl phthalate (MBzP) and mono-(3-carboxypropyl) phthalate (MCPP). Since bilirubin is a potent antioxidant these relationships suggest that phthalates may be associated with increased oxidative stress. Many of the same metabolites were also significantly and positively related with ANC, ALP, and ferritin, suggesting phthalates may be associated with increased inflammation. These markers may be useful in other studies of low-dose exposure to environmental contaminants. PMID- 22085026 TI - Catabolic pathway of gamma-caprolactone in the biocontrol agent Rhodococcus erythropolis. AB - Gamma-caprolactone (GCL) is well-known as a food flavor and has been recently described as a biostimulant molecule promoting the growth of bacteria with biocontrol activity against soft-rot pathogens. Among these biocontrol agents, Rhodococcus erythropolis, characterized by a remarkable metabolic versatility, assimilates various gamma-butyrolactone molecules with a branched-aliphatic chain, such as GCL. The assimilative pathway of GCL in R. erythropolis was investigated by two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) analysis. This analysis suggests the involvement of the lactonase QsdA in ring-opening, a feature confirmed by heterologous expression in Escherichia coli. According to proteome analysis, the open-chain form of GCL was degraded by beta- and omega oxidation coupled to the Krebs cycle and beta-ketoadipate pathway. Ubiquity of qsdA gene among environmental R. erythropolis isolates was verified by PCR. In addition to a previous N-acyl homoserine lactone catabolic function, QsdA may therefore be involved in an intermediate degradative step of cyclic recalcitrant molecules or in synthesis of flavoring lactones. PMID- 22085027 TI - Three-component tandem reaction involving acid chlorides, terminal alkynes, and 2 aminoindole hydrochlorides: synthesis of alpha-carboline derivatives in aqueous conditions via regioselective [3 + 3] cyclocondensation. AB - An efficient synthesis toward highly diversified alpha-carboline derivatives via a three-component tandem reaction using acid chlorides, terminal alkynes, and 2 aminoindole hydrochlorides has been described. The salient feature of the one-pot strategy involves regioselective [3 + 3]-cyclocondensation and the presence of water in the reaction medium to facilitate cyclization. Nonaqueous conditions furnished products in poor yields. PMID- 22085028 TI - Implementing a client-centred approach in rehabilitation: an autoethnography. AB - PURPOSE: Client-centred practice is widely considered a key element of rehabilitation. However, there is limited discussion of how it should be implemented. This study explored how client-centred practice was operationalized during a clinical trial of innovative goal-setting techniques. METHOD: This study drew on principles of co-autoethnography. The personal experiences of three clinical researchers were explored to identify insights into client-centred practice, and seek understanding of this within the broader socio-cultural context. Data were collected through group discussions and written reflections. Thematic analysis and coding were used to identify the dominant themes from the data. RESULTS: The primary way that client-centred practice was operationalized was through listening in order to get to know, to uncover and to understand what was meaningful. Four strategies were identified: utilizing mindful listening, allowing time, supporting clients to prioritize what is meaningful and viewing the therapists' role differently. CONCLUSION: While technical competence in rehabilitation is important, our study suggested a starting point of 'being with' rather than 'doing to' may be beneficial for engaging people in their rehabilitation. We have highlighted a number of practical strategies that can be used to facilitate more client-centred practice. These approaches are consistent with what clients report they want and need from rehabilitation services. PMID- 22085029 TI - Description of two new MICA alleles: MICA*058 and MICA*002:03. AB - We describe two novel alleles, MICA*058 and MICA* 002:03. PMID- 22085030 TI - Multiple stable isotope characterization as a forensic tool to distinguish acid scavenger samples. AB - Acid scavengers are frequently used as stabilizer compounds in a variety of applications. When used to stabilize volatile compounds such as nerve agents, the lower volatility and higher stability of acid scavengers make them more persistent in a post-event forensic setting. Compound-specific isotope analysis of carbon, nitrogen, and hydrogen in three acid-scavenging compounds (N,N diethylaniline, tributylamine, and triethylamine) were used as a tool for distinguishing between different samples. Combined analysis of multiple isotopes improved sample resolution, for instance differentiation between triethylamine samples improved from 80% based on carbon alone to 96% when combining with additional isotope data. The compound-specific methods developed here can be applied to instances where these compounds are not pure, such as when mixed with an agent or when found as a residue. Effective sample matching can be crucial for linking compounds at multiple event sites or linking a supply inventory to an event. PMID- 22085031 TI - NHC-catalyzed enantioselective [2 + 2] and [2 + 2 + 2] cycloadditions of ketenes with isothiocyanates. AB - The enantioselective N-heterocyclic carbene-catalyzed formal [2 + 2] and [2 + 2 + 2] cycloaddition of ketenes and isothiocyanates were developed. Reaction with N aryl isothiocyanates at room temperature favors the [2 + 2] cycloaddition, while reaction with N-benzoyl isothiocyanates at -40 degrees C favors the [2 + 2 + 2] cycloaddition. PMID- 22085032 TI - Efficacy of acitretin for porokeratosis in a child with chronic cutaneous graft versus host disease. AB - Porokeratosis is a rare disorder of epidermal keratinization that is regarded as a precancerous. Recipients of hematopoietic stem cell transplantation (HSCT) have a greater risk of skin cancer; chronic graft versus host disease (GVHD) is an additional risk factor. A 16-year-old boy who had received HSCT for acute myelogenous leukemia was referred to us for sclerodermoid chronic cutaneous GVHD. Two years later, he developed disseminated porokeratosis with a few atypical lesions. Despite cryotherapy, numerous lesions of porokeratosis recurred rapidly. Acitretin resulted in good clinical response and reduced the rate of onset of new lesions. PMID- 22085033 TI - (-)-Epigallocatechin-3-gallate enhances the expression of an insulin-inducible transcription factor gene via a phosphoinositide 3-kinase/atypical protein kinase C lambda pathway. AB - The rat enhancer of split- and hairy-related protein-1 (SHARP-1) is an insulin inducible transcriptional repressor. In this study, we examined issues of whether (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, regulates the expression of the rat SHARP-1 gene and which signaling pathway mediates the regulation. When H4IIE cells were treated with EGCG, SHARP-1 mRNA levels rapidly increased. Pretreatments with inhibitors for either phosphoinositide 3-kinase (PI 3-K) or protein kinase C partially blocked EGCG induction. Atypical protein kinase C lambda (aPKClambda) is known as a downstream target of PI 3-K in the liver. When a dominant-negative form of aPKClambda was expressed, the EGCG induced SHARP-1 mRNAs was inhibited. Finally, Western blot analysis revealed that EGCG rapidly and temporarily stimulates aPKClambda phosphorylation. Thus, we conclude that EGCG induces SHARP-1 gene expression via a PI 3-K/aPKClambda signaling pathway. PMID- 22085034 TI - p-Phenylenediamine and other hair dye sensitizers in Spain. AB - BACKGROUND: Oxidative hair dyes are important skin sensitizers, causing contact allergy and dermatitis in hairdressers and consumers. OBJECTIVES: To study the prevalence of hair dye substances, categorized as potent skin sensitizers, in consumer-available oxidative hair dye products on the market of a southern European country and to compare it with that in Sweden. METHODS: Ingredient labels of 105 oxidative hair dye products from 19 brands were studied, and the prevalence and use pattern of hair dye substances, categorized as potent skin sensitizers, was assessed. Network diagrams were used to display results. RESULTS: According to the labelling, all 105 products contained hair dye substances categorized as potent skin sensitizers. A total of 25 different hair dye substances categorized as potent skin sensitizers were identified. Eighty seven per cent of the products contained at least four such substances. Either p phenylenediamine, toluene-2,5-diamine or toluene-2,5-diamine sulfate was present in 103 products. CONCLUSIONS: Hair dye substances categorized as potent skin sensitizers were used in all studied hair dye products on the Spanish market. The prevalence of p-phenylenediamine was higher in the present study than in a similar study in Sweden. More than 20 potent sensitizers were identified in each country. Not only p-phenylenediamine should be used to diagnose allergy to hair dyes. PMID- 22085035 TI - Efficient exciton funneling in cascaded PbS quantum dot superstructures. AB - Benzenedithiol (BDT) and ethanedithiol (EDT) ligand-exchange treatments can be used to cross-link colloidal PbS quantum dots into nanocrystalline film structures with distinct optoelectronic properties. Such structures can provide a unique platform to study the energy transfer between layers of quantum dots with different sizes. In this report, efficient exciton funneling and recycling of surface state-bound excitons is observed in cascaded PbS quantum dot-based multilayered superstructures, where the excitons transfer from the larger band gap or donor layers to the smallest band gap or acceptor layers. In this system, both the BDT- and EDT-treated cascaded structures exhibit dramatically enhanced photoluminescence from the acceptor layers. As we show, the energy transfer mechanisms involved and their efficiencies are significantly different depending on the ligand-exchange treatment. In the future, we believe these efficient exciton recycling and funneling mechanisms could be used to improve significantly the photocurrent, charge-transport, and conversion efficiencies in low-cost nanocrystalline and hybrid solar cells and the emission efficiencies in hybrid light-emitting devices. PMID- 22085036 TI - Post-War trends in Maori population growth. AB - Abstract Recent levels and trends of mortality and fertility of the minority Maori population of New Zealand are analysed. On this basis two projections for the year 1976 are presented, the first assuming a further rise in life expectation, which has already increased rapidly over the last two decades; and the other that both mortality and the consistently high fertility levels will be reduced. The conclusion is that, regardless of which projection one accepts, growth will be rapid (an increase of 60% to 70% in the period 1961-76), although the age distribution will be different at the youngest ages. Unless fertility is reduced, as in Projection 2, the dependency burden of Maori family heads will be extremely heavy. PMID- 22085037 TI - Breast feeding, fertility and infant mortality: An analysis of some early German data. AB - Abstract Concern about high infant mortality and its suspected connection with the lack of breast-feeding stimulated the collection of statistics about the frequency of breast-feeding in several German states during the late roth and early 20th centuries. Contrary to the assumption that universal and extended breast-feeding is customary among rural agricultural populations, large regional variations existed both in the proportion of children who were breast-fed and in the average duration of the period for which they were breast-fed. An analysis of these data in connection with statistics of infant mortality and marital fertility confirms the association between high infant mortality and the absence of breast-feeding. An hypothesis linking breast-feeding and fertility, however, is not confirmed. Marital fertility appears to be much more closely associated with infant mortality than with breast-feeding. PMID- 22085038 TI - The decline and recovery of the Murut tribe of Sabah. AB - Abstract The Murut tribe of Sabah (formerly North Borneo) numbered 30,300 in 1921, decreased to 18,700 in 1951, and increased again to 22,100 in 1960. In 1951, the tribe was a small diminishing section of a slowly growing population; in 1960 it was increasing itself, and the growth rate of the whole population had shot up. Marked variations in the age structures of the Murut and other indigenous tribes accompanied these changes. Between 1920 and 1960 several investigators attempted to explain the decline, but could not show why only one tribe was failing to hold its own among many others which were increasing. Their findings are summarized, and unpublished data from the 1960 census are given which suggest that increasing contacts with the rest of the population, earlier thought to be an important contributor to the decline, were probably the means of saving the Murut from extinction. PMID- 22085039 TI - Reproductive ideals and educational attainment among white Americans, 1943-1960. AB - Abstract Would the persistent inverse relation between educational attainment and family size in the United States be removed if actual fertility were equal to ideal? Data on ideal family size from 10 national surveys among white Americans of both sexes (from 1943 to 1960) show that gradeschool level respondents have higher ideals than the more educated even when age, religious affiliation, and farm residence are used as controls. Comparison of these ideals with the actual family size or ever-fertile women in the United States indicates that, on the average, the actual family size of all major educational groups falls below the ideal, but the college-educated are furthest from their ideal. If this group lessened the gap between actual and ideal family size, the educational differential in fertility would decrease, but at the price of increasing the rate of population growth. PMID- 22085042 TI - Rapid and accurate identification of genomic species from the Acinetobacter baumannii (Ab) group by MALDI-TOF MS. AB - The closely related members of the Acinetobacter baumannii (Ab) group (A. baumannii, A. pittii and A. nosocomialis) are difficult to identify with phenotypic tests in diagnostic laboratories. Genotypic identification methods require special skills and most do not provide rapid results. The aim of this study was to investigate the ability of MALDI-TOF MS to identify members of the Ab group. Sixty epidemiologically unrelated Acinetobacter spp. isolates were investigated by MALDI-TOF MS: 18 A. baumannii, 17 A. pittii, 18 A. nosocomialis and seven additional isolates representing other Acinetobacter spp. All strains were verified by ARDRA, rRNA intergenic spacer (ITS), recA sequencing and bla(OXA 51) . MALDI-TOF MS correctly identified all the genomic strains but erroneously identified A. nosocomialis as A. baumannii because there was no reference strain within the Bruker database. Peak analysis of individual spectra from representative strains of each member of A. baumannii, A. pittii and A. nosocomialis suggested enough differences between their protein signatures to allow accurate identification using MALDI-TOF MS. Inclusion of specific signature profiles for A. nosocomialis within the Bruker database allowed the correct identification of this genomic species. MALDI-TOF MS spectra can be used as a fast, simple and reliable method to identify members of the Ab group. The rapid and accurate identification of clinically significant Acinetobacter strains will improve insight into their epidemiology and allow for targeted therapeutic and infection control measures against clinically important strains. PMID- 22085043 TI - 'The study has taught me to be supportive of her': empowering women and involving men in microbicide research. AB - Recognising that women often have little control over most HIV-prevention methods, including condoms, researchers have made efforts to develop new bio technological interventions, such as microbicides, that could allow women greater autonomy in HIV-prevention decision making. In many situations, women are unable to negotiate condom use with their partners, meaning that they could be better protected through the use of an effective microbicide. This paper uses qualitative data from the Microbicide Development Programme 301 (MDP301) microbicide trial in Johannesburg, South Africa. Data is taken from in-depth interviews with male partners of female trial participants (n = 28), six focus group discussions involving male partners of trial participants (n = 4) and female participants (n = 2). Data show that men's involvement in microbicide research ranges from a disinterest in trials to the desire to actively take part in and promote research that affects the health of themselves and their partners. Results showed that some participants were reluctant to disclose trial involvement and product use to their partners, making identifying men as potential research participants problematic. This paper considers how to involve men in microbicide research without undermining women's sense of empowerment and ownership of the trial and the product that is being tested. PMID- 22085046 TI - Clinicopathological evaluation of carcinoma cuniculatum: a variant of oral squamous cell carcinoma. AB - Carcinoma cuniculatum (CC) is a rare neoplasm of oral squamous cell carcinoma (OSCC) and remains a histopathological challenge to pathologists because of its low incidence and unique architecture. Therefore, the purpose of this study was to illustrate the clinicopathological findings and biological behavior about this distinctive lesion. Clinical and follow-up information were retrieved from medical charts, and histopathological analyses were performed. Our series included 15 cases of CC, and the study included seven men and eight women, age 44 92. The tongue and mandible were the most frequently affected sites. There were three lymph node metastasis cases, and three local recurrences; one of the patients died of lung metastasis from oral CC. Histopathologically, the point of differential diagnosis with other subtypes of OSCC included unique, cuniculatum architecture and branching crypts. Because of its well-differentiated status, the prognosis of CC is usually optimistic. However, recurrent cases in our study might have possessed invasive biological characters that were not well controlled by conventional treatment; in one case, a portion of the CC transformed into conventional squamous cell carcinoma (SCC). This might suggest that transformed CC rather than primary CC should be further emphasized. PMID- 22085045 TI - The legacy of minimum legal drinking age law changes: long-term effects on suicide and homicide deaths among women. AB - BACKGROUND: Prior to the establishment of the uniform drinking age of 21 in the United States, many states permitted legal purchase of alcohol at younger ages. Lower drinking ages were associated with several adverse outcomes, including elevated rates of suicide and homicide among youth. The objective of this study is to examine whether individuals who were legally permitted to drink prior to age 21 remained at elevated risk in adulthood. METHODS: Analysis of data from the U.S. Multiple Cause of Death files, 1990 to 2004, combined with data on the living population from the U.S. Census and American Community Survey. The assembled data contained records on over 200,000 suicides and 130,000 homicides for individuals born between 1949 and 1972, the years during which the drinking age was in flux. Logistic regression models were used to evaluate whether adults who were legally permitted to drink prior to age 21 were at elevated risk for death by these causes. A quasi-experimental analytical approach was employed, which incorporated state and birth-year fixed effects to account for unobserved covariates associated with policy exposure. RESULTS: In the population as a whole, we found no association between minimum drinking age and homicide or suicide. However, significant policy-by-sex interactions were observed for both outcomes, such that women exposed to permissive drinking age laws were at higher risk for both suicide (OR = 1.12, 95% CI: 1.05, 1.18, p = 0.0003) and homicide (OR = 1.15, 95% CI: 1.04, 1.25, p = 0.0028). Effect sizes were stronger for the portion of the cohort born after 1960, whereas no significant effects were observed for women born prior to 1960. CONCLUSIONS: Lower drinking ages may result in persistent elevated risk for suicide and homicide among women born after 1960. The national drinking age of 21 may be preventing about 600 suicides and 600 homicides annually. PMID- 22085047 TI - Impedance-based detection of beating rhythm and proarrhythmic effects of compounds on stem cell-derived cardiomyocytes. AB - The xCELLigence real time cell analyzer Cardio system offers a new system for real-time cell analysis that measures impedance-based signals in a label-free noninvasive manner. The aim of this study was to test whether impedance readings are a useful tool to detect compound effects on beating frequency (beats per minute, bpm) and arrhythmias of human induced pluripotent stem cell- and a mouse embryonic stem cell-derived cardiomyocyte line (hiPSC-CM and mESC-CM, respectively). Baseline values for control wells were 45+/-3 and 179+/-6 bpm, respectively (n=6). Correspondingly, isoproterenol increased beating frequency by 77% and 71%, whereas carbachol decreased frequency by 11% and 100% (stopped in 5/6 mESC-CM wells). E-4031 decreased beating rate and caused arrhythmias in both cell types, however, more pronounced in the human iPSC-CMs. Amlodipine inhibited contractions in both models, and T-type calcium channel block strongly reduced beating rate and eventually stopped beating in mESC-CM but caused a smaller effect in hiPSC-CM. The results of this initial study show that, under the right conditions, the beating frequency of a monolayer of cells can be stably recorded over several days. Additionally, the system detects changes in beating frequency and amplitude caused by added reference compounds. This assay system has the potential to enable medium-throughput screening, but for implementation into routine daily work, extended validation, testing of additional batches of cardiomyocytes, and further assay optimization (e.g., frequency of media exchange, growth matrix, seeding density, age of cells after plating, and temperature control) will be needed. PMID- 22085048 TI - Mussel-inspired anchoring for patterning cells using polydopamine. AB - This Article introduces a simple method of cell patterning, inspired by the mussel anchoring protein. Polydopamine (PDA), artificial polymers made from self polymerization of dopamine (a molecule that resembles mussel-adhesive proteins), has recently been studied for its ability to make modifications on surfaces in aqueous solutions. We explored the interfacial interaction between PDA and poly(ethylene glycol) (PEG) using microcontact printing (MUCP). We patterned PDA on several substrates such as glass, polystyrene, and poly(dimethylsiloxane) and realized spatially defined anchoring of mammalian cells as well as bacteria. We applied our system in investigating the relationship between areas of mammalian nuclei and that of the cells. The combination of PDA and PEG enables us to make cell patterns on common laboratorial materials in a mild and convenient fashion. PMID- 22085049 TI - Human mitochondrial ATP-binding cassette transporter ABCB10 is required for efficient red blood cell development. PMID- 22085050 TI - Training junior doctors. PMID- 22085051 TI - Denis Hawkins Memorial Award Recipient 2011. PMID- 22085052 TI - SHARING-improving and documentation of handover: mind the gap. AB - The dangers of incomplete or inadequate handover as trainee doctors change shifts are all too apparent. This paper describes SHARING as a systematic method of transferring information and responsibility. PMID- 22085053 TI - Structured multidisciplinary intershift handover (SMITH): a tool for promoting safer intrapartum care. AB - On the labour ward, the key to achieving patient safety is the intershift handover, which affords an opportunity for the team to undertake a baseline assessment of the current situation, anticipate problems, plan contingencies and subsequently maintain situational awareness. If optimised, the handover has immense potential not only for enhancing patient safety but also for reducing stress to staff. The handover should be regarded not as an end but as the beginning of the process of maintaining individual and team situational awareness throughout the shift. Each maternity unit should have a Structured Multidisciplinary Intershift Handover (SMITH) protocol, which encompasses pre handover, handover and post-handover guidance. This paper describes the underlying principles, benefits and content of a SMITH protocol. PMID- 22085054 TI - How good are obstetric and gynaecology trainees at reviewing and debriefing their patients following operative deliveries? AB - High levels of obstetric involvement are associated with psychological morbidity in patients postnatally. Operative deliveries contribute to up to 40% of deliveries. Given this, we decided to assess how well patients were being reviewed and debriefed following operative deliveries within our unit. A total of 53 notes following operative deliveries were analysed. To assess the quality of debriefing, the notes were reviewed for evidence of documentation on discussion for reason, procedure and complications of mode of delivery, advised plan for next delivery and contraception advice. Feedback questionnaires were given to patients on discharge to complete, regarding their understanding on the events surrounding their delivery. To assess how well doctors reviewed their own deliveries, we searched the notes for documented evidence of primary operator review. Our results identify significant deficiencies in doctors reviewing and debriefing patients following operative deliveries. PMID- 22085055 TI - Prioritisation of teaching topics in obstetrics and gynaecology: a Delphi survey of postgraduate trainees. AB - Topics for theoretical teaching during the obstetrics and gynaecology specialty training programme are often chosen by tutors, with little input from the trainees. However, it is important to actively involve adults in their learning process to maintain their learning ownership and motivation. The Delphi methodology is a generic social science technique used to aggregate views and opinions of experts, the community and service users. In this study, we conducted a two generational Delphi study to achieve consensus between a group of trainees in obstetrics and gynaecology, regarding what they considered important topics for inclusion in their protected teaching programme. A total of 25 trainees from one deanery, participated in this study. We were able to produce a list of 26 topics in obstetrics and 30 in gynaecology, prioritised according to their importance for inclusion in the specialty protected teaching programme, as viewed by these trainees. PMID- 22085056 TI - Dr Robert Lawson Tait: the forgotten gynaecologist. PMID- 22085057 TI - Meta-analysis of sex difference in testosterone levels in umbilical cord blood. AB - This meta-analysis reviewed published literature comparing human male and female umbilical cord total testosterone (T) levels. A total of 18 studies using 1,229 samples from 602 male and 627 female newborns were analysed using the RevMan 5 statistical package. Analysis using the inverse variance method based on a random effects model revealed significantly higher cord T in boys than girls at a moderate effect size (Hedges' g = 0.57). There was significant heterogeneity between the 18 studies, although the five studies using direct assays showed no heterogeneity. For studies using extraction and chromatography, those that combined T from arterial and venous cord blood found a larger sex difference than those using only cord venous samples (Hedges' g = 0.94 vs 0.32); this suggests umbilical cord venous T is of maternal/placental origin and arterial T is of fetal origin. The wide range of T values between studies suggests high cross reactivity in the assay methods reviewed. PMID- 22085058 TI - The emergency contraceptive drug, levonorgestrel: a review of post-coital oral and peri-coital vaginal administration for prevention of pregnancy. AB - The objective of our study was the evaluation and elucidation of levonorgestrel (LNG) as emergency contraception (EC) administered through oral and vaginal routes. Data regarding post-coital oral and peri-coital vaginal application of LNG were extracted from the literature through MEDLINE database service for years 2001-2010. It was found that a single dose of 1.5 mg LNG or two doses of 0.75 mg LNG 12 h apart were used for EC. Currently, LNG is also on trial for vaginal application as EC in Carraguard gel for 'dual protection'. The oral or vaginal dose of 1.5 mg LNG resulted in peak plasma concentration, C(max) 19.2 or 3.21 ng/ml, with shorter time, T(max) 1.4 or 6.6 h, and greater AUC, 152.7 or 52.5 ng.h/ml, with shorter half-life, 25 or 32 h, respectively. LNG EC inhibited mid cycle LH surge and delayed or prevented ovulation when administered before ovulation. Mechanism of action of LNG EC appeared to inhibit or delay ovulation. The risk of pregnancy was 4.12%. A single dose of 1.5 mg LNG could reduce the pregnancy rate to 0.7%. Occurrence of ectopic pregnancy following failure of LNG EC was reported. This EC caused no serious adverse effects but was associated with menstrual disturbance. Although widely acceptable, the cost and short-supply to rural areas pose a barrier to access EC for the poor and rural-dwellers, respectively. It was concluded that unlike post-coital oral administration, peri coital vaginal application of 1.5 mg LNG needs further study to be an alternative option for women to use it for prevention of pregnancy. PMID- 22085059 TI - Hyperemesis gravidarum: current aspect. AB - An advanced state of nausea and vomiting, which are common symptoms of early pregnancy, is known as hyperemesis gravidarum and may result in dehydration, ketonuria, catabolism and require hospitalisation. Aetiological factors include increased hCG and steroids, multiple pregnancy and vitamin deficiency. Differential diagnosis of nausea and vomiting should be made and supportive treatment as well as antiemetic therapy is recommended. This review discusses aetiology and management modalities of hyperemesis gravidarum including fluid therapy, antiemetics, vitamins, psychological support and non-pharmacological measures. PMID- 22085060 TI - Operative complications and fetal morbidity encountered in 300 prophylactic transabdominal cervical cerclage procedures by one obstetric surgeon. AB - This retrospective cohort study identifies complications associated with transabdominal cerclage (TAC). In 300 procedures performed over a 24 year time span, 11 (3.7%) surgical complications were encountered. Fetal loss (prior to 20 weeks) occurred in 4.1% of pregnancies. The median estimated blood loss among patients was 100 ml, with blood loss sufficient to require transfusion only once. Considering patients with classical indications, the gestational age at delivery was greater (37 weeks) after TAC than in the latest pre-TAC pregnancy (24 weeks) (p < 0.001). Lower uterine dehiscence in four patients and uterine rupture in one, underscore the advisability of early term delivery after fetal lung maturity is assured. A survival rate of 98.0% was calculated among infants that were delivered at >24 weeks' gestation. Our results demonstrate that complications encountered in placing a TAC were unusual and generally manageable. This communication may assist the surgeon to balance risks in individual clinical circumstances more adequately. PMID- 22085061 TI - Demographic and clinical variables influencing gestational age at booking among South African pregnant women. AB - A retrospective record review was made of 758 women who delivered over a 2-month period at the Charlottee Maxeke Johannesburg Academic Hospital. Women booking early (up to 14 weeks) were compared with women booking late (from 15 weeks onwards). A total of 45 (6%) and 713 (94%) women booked in the early and late groups, respectively. Women of white ethnicity and women who experienced previous fetal loss booked significantly early. Primigravidae booked significantly late. PMID- 22085062 TI - Born before arrival births: impact of a changing obstetric population. AB - This retrospective cohort study examined 143/39,895 (0.36%) consecutive born before-arrival (BBA) births. The incidence of BBA births doubled from 0.26% in 2005 to 0.5% in 2009. This increase was mainly attributed to the increase of non Irish nationals and patients from low socioeconomic groups attending for antenatal care. Poor social background was often coupled with current or past substance misuse and/or a diagnosis of an infectious disease. While there was no excess in maternal morbidity, the perinatal mortality rate among BBA births was three-fold increased (27.9/1,000) when compared with the overall rate for all inborn babies in our hospital (8.5/1,000) but significantly less than previously published (58.4/1,000). Results of our study call for continuing training of paramedic staff involved in these deliveries and neonatal resuscitation. Given the easy accessibility of antenatal services in Ireland, this study highlights the urgent need for optimising parental education and care in this vulnerable group of patients. PMID- 22085063 TI - Effect of nalbuphine hydrochloride on the active phase during first stage of labour: a pilot study. AB - The aim of this pilot study was to determine whether nalbuphine shortens the duration of the active phase during the first stage of labour in pregnant women. Among 1,619 deliveries, we enrolled 302 pregnant women between March 2003 and August 2005. The case group received a nalbuphine injection (n = 57), while the remaining patients served as a control group (n = 245). The effects of nalbuphine on the length of labour were analysed using a survival analysis (log-rank test). The average duration of the initial active phase was 75 and 160 min for the case and control groups, respectively. The reduced duration of the active phase in the case group occurred regardless of oxytocin infusion (p < 0.01) and was without significant risks. PMID- 22085064 TI - Repeat caesarean delivery as a risk factor for abnormal blood loss, blood transfusion and perinatal mortality. AB - We reviewed 450 cases of caesarean delivery (January-December 2009) at the University of Ilorin Teaching Hospital in Nigeria. We analysed the association between caesarean delivery status (primary or previous) and the following outcomes: abnormal blood-loss, blood transfusion and perinatal mortality. Although significant differences were observed between primary and previous caesarean delivery groups in regards to maternal age, urgency of the caesarean delivery, booking status, and cadre of birth attendant staff, no association was noted between caesarean delivery status and any of the three outcomes. Further analyses identified parity as an important predictor for blood transfusion and abnormal blood loss. In addition, we found a dose?response relationship between parity and abnormal blood loss (< 0.05). Also, mothers with an emergency caesarean delivery of the index pregnancy were more than twice as likely to have a blood transfusion as compared with those with an elective caesarean delivery. PMID- 22085065 TI - Does carbetocin for prevention of postpartum haemorrhage at caesarean section provide clinical or financial benefit compared with oxytocin? AB - Postpartum haemorrhage is a major cause of maternal morbidity and mortality worldwide. A recent Cochrane review of carbetocin (long-acting oxytocin analogue) concluded that its use decreased additional uterotonic requirements, however, no included studies compared its use against intravenous bolus oxytocin. The majority of studies of carbetocin have considered its use in vaginal delivery; no studies have examined the economic implications of its use. This study describes a clinical and financial evaluation undertaken at a United Kingdom District General Hospital surrounding the introduction of carbetocin for prophylaxis against postpartum haemorrhage at caesarean deliveries. A range of clinical outcomes were observed including frequency of postpartum haemorrhage, estimated blood loss, transfusion requirements, change in haemoglobin or haemodynamics, use of additional uterotonics and perioperative recovery. Finally, a composite financial analysis was performed. No clinically significant benefit was found, however associated costs increased by L18.52/patient. PMID- 22085066 TI - Is peripartum zidovudine absolutely necessary for patients with a viral load less than 1,000 copies/ml? AB - Late access to obstetrics service, viral load of >1,000 copies/ml and short duration antenatal highly active antiretroviral treatment (HAART), are the strongest predictors for mother-to-child transmission (MTCT). Neonatal triple therapy did not seem to reduce MTCT if the above risk factors were present. Intrapartum intravenous zidovudine (i.v. ZDV) of <4 h does not seem to increase the risk of MTCT if the viral load is <1,000 in those receiving HAART. Intrapartum i.v. ZDV >4 h did not seem to reduce the risk of MTCT with the viral load >1,000 in patients having <4 weeks of HAART. PMID- 22085067 TI - Cost-effectiveness of ultrasound use by on-call registrars in an acute gynaecology setting. AB - Ultrasound, and in particular transvaginal sonography (TVS), plays an important role in the management of women with acute gynaecology conditions. This study compared the cost-effectiveness of two models of out-of-hours care for women in an acute gynaecology setting. In the ultrasound-based model, the on-call registrar with ultrasound experience managed such patients after performing pelvic ultrasound as a part of the initial assessment. On the other hand, in the traditional model of care the on-call registrar managed the patients without the use of ultrasound. The conclusion is that the use of ultrasound by the on-call registrars has significant cost implications through reduced hospital admissions. It leads to improved outcomes of such patients through timely diagnosis and treatment. PMID- 22085068 TI - Fluoroscopy-guided, transcervical, selective salpingography and fallopian tube recanalisation. AB - This study is a retrospective review of the transcervical fluoroscopy-guided fallopian tube recanalisation (FTR) procedures done in a multi-ethnic south-east Asian population, over 9 years. A total of 100 patients with infertility and documented proximal tubal obstruction (PTO) were referred for FTR. On-table hysterosalpingography under sedation demonstrated true PTO in 96 patients. At selective-salpingography, the PTO cleared in 16 patients; 78 required FTR and two had fimbrial blockage. The technical success rate of FTR was 86.8% and the post FTR pregnancy rate was 36.84% at a mean follow-up interval of 12.2 months. There were no major, immediate procedure-related complications. There was an ectopic pregnancy in a single treated patient. Fluoroscopy-guided FTR is a safe treatment option in patients with infertility from PTO, with high technical success rate, low complication rate and increased chances of pregnancy; therefore it should be preferred before attempting more expensive and resource-intensive procedures. PMID- 22085069 TI - The social adaptation of children born after ICSI compared with IVF-conceived children: a study from China. AB - We compared the social adjustment among Chinese children born after intracytoplasmic sperm injection (ICSI) vs those after in vitro fertilisation (IVF) and identify factors related to the adjustment. The social adaptation of 86 ICSI and 165 IVF conceived children of 4-6 years of age was assessed using the Infants-Junior Middle School Students' Social-Life Abilities Scale. There was no significant difference between the ICSI and IVF-conceived groups on the item of communication, self-dependence, locomotion, work skills, socialisation, self management and total scores. Compared with routine IVF, ICSI does no harm to the social adaptation of children conceived through this technology. PMID- 22085070 TI - Impact of improving outcome guidance in gynaecological cancer on squamous cell carcinoma of the vulva in the West Midlands, UK. AB - This study aimed to assess the benefits and outcomes of squamous cell carcinoma (SCC) of the vulva managed in a cancer centre post-centralisation of cancer care in the UK. A retrospective study was performed to evaluate the demography and management outcomes of SCC of the vulva in a regional gynaecological cancer centre. The results were then compared with the Rhodes et al. (1998) population based study. Over the years, disease demography remained largely unchanged. However, centralisation of cancer care has resulted in significant changes in the pattern of care. The number of cases managed has increased by 1.7 times and the permutation of surgeries have reduced from 15 to 4. There is also a significant increased in the number of lymphadenectomies performed (p = 0.003). These changes were accompanied by improvement in 5-year cause-specific survival (p = 0.055). PMID- 22085071 TI - Prevalence of cervical squamous intraepithelial lesions among HIV-positive women in Enugu, South-eastern Nigeria. AB - HIV infection is a risk factor for cervical cancer and both diseases are prevalent in Nigeria. The study determined the prevalence of cervical squamous intraepithelial lesion (SIL) among HIV-positive women in Enugu state, which has the highest HIV burden in South-eastern Nigeria. Pap smear was carried out on 150 HIV-positive (HIV+ve) women and 150 HIV-negative (HIV?ve) controls at the University of Nigeria Teaching Hospital, Enugu, Nigeria from December 2007 to March 2008. The prevalence of SIL for the HIV+ve group and the control group were 12.6% and 4.6%, respectively (p = 0.014). Also, the prevalence of each category of SIL identified in the study, was higher among the HIV+ve group. There is an association between HIV infection and SIL in Enugu, South-eastern Nigeria. Cervical cancer screening should be incorporated into the antiretroviral (ARV) clinics, so as to prevent the impending surge in the burden of cervical cancer in Nigeria. PMID- 22085072 TI - Knowledge and perception of the Nigerian Abortion Law by abortion seekers in south-eastern Nigeria. AB - One in four pregnancies worldwide is voluntarily terminated. Approximately 20 million terminations are performed under unsafe conditions, mostly in developing countries with restrictive abortion laws. A total of 100 consecutive abortion seekers were interviewed, to ascertain their knowledge and perceptions on the Nigerian Abortion Law. The majority (55.0%) of the respondents were students. Most of them (97%) had at least secondary education and the majority (62.0%) were within the 20-24 years age range. Only 31.0% of the women interviewed were aware of the Nigerian Abortion Law. While 16% perceived the law as being restrictive, 2% opined that' it was alright'; 1% perceived it as very restrictive and 12% had no opinion on the abortion law. Knowledge of the abortion law had no significant relationship with either the educational level of the respondent or the number of previous pregnancy terminations and overall demand for abortion services. It is necessary to ensure a wide dissemination of the abortion law and its provisions to the Nigerian public, in order to arm them with the necessary information to participate actively in debates on abortion law reforms. PMID- 22085073 TI - Twin pregnancy with complete hydatidiform mole and co-existent viable fetus. PMID- 22085074 TI - Triplet pregnancy with complete hydatidiform mole co-existing with two viable fetuses. PMID- 22085075 TI - Giant lingual granuloma gravidarum. PMID- 22085076 TI - Prenatal diagnosis of craniosynostosis: sonographic features of Muenke syndrome. PMID- 22085077 TI - Spontaneous uterine rupture during the 1st trimester: a rare but life-threatening emergency. PMID- 22085078 TI - Florid cystic endosalpingiosis with extensive peritoneal involvement and concurrent bilateral ovarian serous cystadenoma. PMID- 22085079 TI - Successful Thermachoice endometrial ablation immediately following uterine perforation at microwave endometrial ablation. PMID- 22085080 TI - Endometrial ossification in postmenopausal women. PMID- 22085083 TI - Acceptability of an "on-demand" pre-exposure HIV prophylaxis trial among men who have sex with men living in France. AB - Although predictors of willingness to take daily, self-administered pre-exposure HIV prophylaxis (PrEP) for men who have sex with men (MSM) have been studied in the context of several PrEP trials internationally, little is known about MSM interested in participating in a trial on the use of PrEP on an "on -demand" basis, i.e., taking a first dose of combined tenofovir/emtricitabine a few hours before possible HIV sexual exposure and a second dose a few hours afterwards. A double-blind placebo randomized PrEP trial will soon begin in France to evaluate the effectiveness of PrEP in terms of reducing HIV infection rates, among MSM self-administering "on-demand" PrEP. To assess potential participants' characteristics associated with willingness to participate in the trial and identify barriers and facilitators to implementation, MSM completed a self administered questionnaire, distributed via gay venues and community websites. Among the 443 respondents who reported being HIV-negative, 40% reported being interested in participating. Factors independently associated with interest included: reporting lower educational level, more than 20 male sexual partners in the previous year, reporting unprotected anal sex with casual partners and preferring PrEP follow-up visits in a devoted area within a hospital. There is great interest in participating in a future "on-demand" PrEP trial among HIV negative MSM and particularly in those at potentially high risk of HIV exposure. Providing confidentiality and tailored counseling during PrEP follow-up are important issues. PMID- 22085084 TI - Templated synthesis of metal nanorods in silica nanotubes. AB - We report a general method for the synthesis of noble metal nanorods, including Au, Ag, Pt, and Pd, based on their seeded growth in silica nanotube templates. The controlled growth of the metals occurs exclusively on the seeds inside the silica nanotubes, which act as hard templates to confine the one-dimensional growth of the metal nanorods and define their aspect ratios. This method affords large quantities of noble metal nanorods with well-controlled aspect ratios and high yield, which may find wide use in the fields of nanophotonics, catalysis, sensing, imaging, and biomedicine. PMID- 22085085 TI - Continuous photochemical generation of catalytically active [CpRu]+ complexes from CpRu(eta6-C6H6)PF6. AB - Inter- and intramolecular ene-yne coupling reactions catalyzed by a species generated in situ via photolysis of CpRu(eta(6)-C(6)H(6))PF(6)--an inexpensive, readily available, and shelf-stable complex--have been demonstrated under conditions of continuous flow. Importantly, the catalyst can be recovered quantitatively at the end of the reaction. Various functional groups are tolerated by the reaction, which affords skipped diene products in high yields. PMID- 22085086 TI - Detailed characterization of proanthocyanidins in skin, seeds, and wine of Shiraz and Cabernet Sauvignon wine grapes (Vitis vinifera). AB - The distribution of proanthocyanidin (PA) polymer lengths, proanthocyanidin concentration at each polymer length, and polymer composition were determined in the seed, skin, and wine of Shiraz and Cabernet Sauvignon grape berries grown in southeast Australia. PA was fractionated by semipreparative high performance liquid chromatography (HPLC) and analyzed by phloroglucinolysis and HPLC to report the degree of polymerization (DP), concentration, and composition at 11 DP values in seed and wine and 21 DP values in skin. In skin, the highest PA concentration was observed at a DP of 31 in Shiraz and 29 in Cabernet Sauvignon representing 15% of the total PA in both varieties. The distribution of seed PA had the highest concentration at a DP of 7 in Shiraz and 6 in Cabernet Sauvignon representing around 30% of the total PA. In the wine PA distribution, the highest concentration was observed at a DP of 11 in Shiraz and 9 in Cabernet Sauvignon representing around 26 and 32% of the distribution, respectively. A second peak in wine PA concentration was observed at the largest DP of 18 in Shiraz and 15 in Cabernet Sauvignon representing around 20% of the distribution. The composition in wine did not vary at different DP, but the proportion of epicatechin gallate varied in seed PA less than 4 DP. The proportion of epigallocatechin increased with increasing DP in skin PA. Wine PA had a DP range and composition similar to the distribution of skin PA between DP 4 and 18 suggesting that larger skin PAs are not extracted into wine. This study provides information that could be used to target the important PA fractions in grapes that need to be measured to understand (or predict) PA extraction into wine and eventual mouthfeel. PMID- 22085087 TI - A survey of community exercise programmes for stroke survivors in Scotland. AB - Stroke is the most common cause of complex disability in the community. Physical fitness is often reduced after stroke, but training can improve fitness and function. UK and international stroke clinical guidelines recommend long-term exercise participation for stroke survivors. However, there has been no previous research into what services are available to support this. In 2009, we conducted the first European survey of community Exercise after Stroke services. A link to our web-based survey was emailed to health, leisure service and stroke charity contacts in Scotland with email and telephone follow-up to non-respondents. The overall response rate was 64% (230/361). A total of 14 Exercise after Stroke services were identified, the majority of which were run by charity collaborations (7/14), followed by leisure centre services (4/14) and health services (3/14). We sought information on session content, referral and assessment processes, and the qualifications of exercise instructors. This information was cross-referenced with current clinical and exercise guidelines to determine whether existing resources were sufficient to meet stroke survivors' needs for safe, effective and sustainable access to exercise. The results indicated a shortage of stroke-specific community exercise programmes. Further service development is required to ensure appropriate instructor training and referral pathways are in place to enable stroke survivors to access exercise services in accordance with current guidelines. PMID- 22085089 TI - A 90th anniversary of AOGS and onwards. PMID- 22085088 TI - Modeling the relative GHG emissions of conventional and shale gas production. AB - Recent reports show growing reserves of unconventional gas are available and that there is an appetite from policy makers, industry, and others to better understand the GHG impact of exploiting reserves such as shale gas. There is little publicly available data comparing unconventional and conventional gas production. Existing studies rely on national inventories, but it is not generally possible to separate emissions from unconventional and conventional sources within these totals. Even if unconventional and conventional sites had been listed separately, it would not be possible to eliminate site-specific factors to compare gas production methods on an equal footing. To address this difficulty, the emissions of gas production have instead been modeled. In this way, parameters common to both methods of production can be held constant, while allowing those parameters which differentiate unconventional gas and conventional gas production to vary. The results are placed into the context of power generation, to give a "well-to-wire" (WtW) intensity. It was estimated that shale gas typically has a WtW emissions intensity about 1.8-2.4% higher than conventional gas, arising mainly from higher methane releases in well completion. Even using extreme assumptions, it was found that WtW emissions from shale gas need be no more than 15% higher than conventional gas if flaring or recovery measures are used. In all cases considered, the WtW emissions of shale gas powergen are significantly lower than those of coal. PMID- 22085090 TI - Contribution of proteomics to the study of plant pathogenic fungi. AB - Phytopathogenic fungi are one of the most damaging plant parasitic organisms, and can cause serious diseases and important yield losses in crops. The study of the biology of these microorganisms and the interaction with their hosts has experienced great advances in recent years due to the development of moderm, holistic and high-throughput -omic techniques, together with the increasing number of genome sequencing projects and the development of mutants and reverse genetics tools. We highlight among these -omic techniques the importance of proteomics, which has become a relevant tool in plant-fungus pathosystem research. Proteomics intends to identify gene products with a key role in pathogenicity and virulence. These studies would help in the search of key protein targets and in the development of agrochemicals, which may open new ways for crop disease diagnosis and protection. In this review, we made an overview on the contribution of proteomics to the knowledge of life cycle, infection mechanisms, and virulence of the plant pathogenic fungi. Data from current, innovative literature, according to both methodological and experimental systems, were summarized and discussed. Specific sections were devoted to the most studied fungal phytopathogens: Botrytis cinerea, Sclerotinia sclerotiorum, and Fusarium graminearum. PMID- 22085091 TI - An unusual presentation of subcutaneous granuloma annulare in association with juvenile-onset diabetes: case report and literature review. AB - Subcutaneous granuloma annulare (SGA) is a rarely reported subtype of granuloma annulare that occurs almost exclusively in children. The etiology of these lesions is unknown, although a possible relationship to insulin-dependent diabetes mellitus (IDDM) has been proposed in the literature. Here we present an unusual case of SGA on the right forearm in a 3-year-old girl. Unlike the typical lesions noted on the extremities, on magnetic resonance imaging her lesions involved the subcutaneous tissue and adjacent muscles in multiple locations. Histopathologically, the case was consistent with SGA but was unusual in its distribution involving multiple muscles, a finding that has not been previously reported. Weeks after incisional biopsy, she was readmitted with diabetic ketoacidosis (DKA) secondary to IDDM. After treatment of her DKA and control of her glycemia, the forearm SGA vanished, which supported the pathologic diagnosis and alleviated our concerns secondary to the unusual distribution. PMID- 22085093 TI - A fatal elephant attack. AB - A rare case of an elephant attack is presented. A 44-year-old man working as an elephant keeper was attacked by a cow elephant when he tripped over a foot chain while the animal was being medically treated. The man fell down and was consequently repeatedly attacked with elephant tusks. The man sustained multiple stab injuries to both groin regions, a penetrating injury to the abdominal wall with traumatic prolapse of the loops of the small bowel, multiple defects of the mesentery, and incomplete laceration of the abdominal aorta with massive bleeding into the abdominal cavity. In addition to the penetrating injuries, the man sustained multiple rib fractures with contusion of both lungs and laceration of the right lobe of the liver, and comminuted fractures of the pelvic arch and left femoral body. The man died shortly after he had been received at the hospital. The cause of death was attributed to traumatic shock. PMID- 22085092 TI - The incidence and risk factors of invasive fungal infection after haploidentical haematopoietic stem cell transplantation without in vitro T-cell depletion. AB - In recent years, we have successfully established a novel method of haploidentical haematopoietic stem cell transplantation (HSCT) without in vitro T cell depletion. This study was aimed at analysing the incidence and risk factors of invasive fungal infection (IFI) with this transplantation method. The study comprised 291 patients who had undergone haploidentical HSCT from 1 January 2007 to 31 December 2008. IFI was diagnosed according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group 2002 criteria, and only proven or probable cases of IFI were regarded as true cases. A total of 39 patients were documented as having IFI, including four proven cases and 35 probable cases. The median time of diagnosis was 26 days (range: 6-405 days) after transplantation. The cumulative incidence rates of IFI at 40 days, 1 year, 2 years and 3 years after transplantation were 8.25%, 13.1%, 13.4% and 13.4%, respectively. Multivariate analysis identified platelet engraftment time (>17 days) (p 0.027; hazard ratio (HR) 2.432; 95% CI 1.105-5.355), a high risk of underlying disease (p 0.001; HR 2.916; 95% CI 1.515-5.611) and grade III-IV acute graft-versus-host disease (p 0.019; HR 2.407; 95% CI 1.154-5.022) as risk factors for IFI. The incidence rates of IFI in patients with no, one, two or three risk factors at 3 years after transplantation were 4.48%, 7.86%, 29.6% and 23.1%, respectively. In conclusion, IFI is an important complication following haploidentical HSCT without in vitro T-cell depletion. PMID- 22085094 TI - Cigarette smoking and widowhood in the United States. AB - Abstract Extract In the United States, for newly married couples with husband aged 23 and wife 21 who never divorce or re-marry after death of spouse, expectation of married life increased by 10.1 years between 1910 and 1965. Expectation of widowed life decreased by 3.2 years for husbands, but, despite large mortality declines for both sexes, increased by 1.8 years for wives. These and related data are shown in Table 1. PMID- 22085095 TI - On the incidence of illegal abortion. AB - Abstract If the medical, social, and demographic effects of the Abortion Act are to be properly assessed, it is essential to have reliable estimates of the number of abortions illegally procured in Britain before the Act came into operation on 27th April 1968. There is, at present, no agreement on what this figure is likely to have been, and published estimates range from several hundreds of thousands down to about 15,000 a year. For example, in 1950, Dr Eustace Chesser published 'a most conservative estimate that the figure cannot be less than a quarter of a million every year',l though 100,000 was the figure most often quoted before the law was changed. And in a recent study of the first three years of the Act Mrs. Madeleine Simms, who was much concerned as General Secretary of the Abortion Law Reform Association at the time, has said that 'during parliamentary debates on the Abortion Act, the Home Secretary used this as his base-line figure'.2 Since this was upgraded in press reports of her article to 'the official figure used by the Home Secretary, for the number of criminal abortions each year was 100,000',3 it may be useful to recall that what Mr Roy Jenkins, who was then Home Secretary, actually said was 'perhaps as many as 100,000 illegal operations a year take place'.4 This was in the course of a speech supporting a Private Member's Bill upon which the government's collective attitude was one of neutrality, and which Mr Jenkins therefore very properly prefaced by saying 'I am speaking for myself, as I am entided to do, as is any other hon. member, and on my own responsibility'. So whether or not this estimate was correct, it plainly has no authority as 'the official figure' and, in fact, no official estimate ever does appear to have been published, either by the Home Office or by any other government agency. PMID- 22085096 TI - High foetal mortality and birth intervals. AB - Abstract Studies of birth intervals have generally separated the process into: (1) the period of infertility following a pregnancy termination; (2) the length ofthe interval from the end of the infertile period to the next conception (which reflects the probability of conception), and (3) the average duration of pregnancy for both live births and foetal deaths.(1) Empirically derived intervals between successive live births average from 19 to 30 lunar months(2) (Table 1), depending upon the population studied and the birth order.(3) Estimates of conception rates using birth intervals data require some estimate of the extent to which foetal wastage increases the birth interval. PMID- 22085097 TI - Family structure and socio-economic differentials in fertility. AB - Abstract The long standing research on the relation of socio-economic status and fertility has recently given way to a focus on those factors which account for class differentials. Although class differences in fertility seem to be diminishing, the basic relationship remains inverse.(2) In an attempt to explain class differentials in fertility, researchers have begun to look at such variables as age at marriage(3), value orientations(4), and non-fiunilial activity.(5) Bumpass demonstrated that age at marriage is an interaction variable which greatly attenuates the relationship between social class and fertility. He found that the relationship was inverse among women marrying before age 19, but direct among women who were 23 years or older at first marriage. Clifford examined value orientations as an intervening variable in the socio-economic status-fertility relationship. Modern and traditional value orientations did aid in interpreting the relationship, but other factors were also operative. Kupinsky found that the non-familial activity of women decidedly influenced socio-economic differentials infertility. Thelabour force participation of women had a greater effect on reducing fertility among upper-status women than among those of lower status. This relationship was also influenced by the rural-urban background of the women. PMID- 22085098 TI - The size and structure of residential families, Guatemala City, 1964. AB - Abstract In a review of census data for the periods 1945-54 and 1955-63, Burch discloses an increasing tendency for average household sizes to cluster at five to six members for developing nations, compared to three to four for developed nations.(1) Also, among developing nations he finds less than 50% of the population living in households containing three to six persons. This apparently contradicts Levy's general rule which prompted his study, that 'for well over 50% of the members of ... all known societies in world history' actual family size and composition have varied much less than would be expected, given ideal rules of residence which can vary from the classical extended family of Asian renown and European history to the small 'isolated' nuclear family of the modernized West.(2). PMID- 22085099 TI - Urbanization, non-familial work, education, and fertility in Taiwan. AB - Abstract It is well known, that there is a relationship between the level of development of a society and its level offertility.(1) However, it is not clear which of the complex ofvariables associated with development are primarily associated with the reduction of fertility. Urbanization, female labour force participation and education are three of the variables most commonly cited as bearing a causal relationship to fertility. Urbanization implies a change of environment of a substantial portion of the population which may result in a change in the value placed on large families. This is particularly true when urban mortality is lower than rural, so that more children survive.(2) However, it has also been argued that urbanization results in a change in family structure from the extended to the nuclear family with a concomitant reduction in the value placed on having many children.(3) Additional changes in family patterns which are sometimes said to explain fertility reduction due to urbanization are increases in the proportion of women never marrying and increases in the age at marriage. PMID- 22085100 TI - Individual mobility in a stationary population. AB - Abstract An increasing population facilitates individual mobility. One of the consequences of moving towards the inevitable stationary population is that mobility will become more difficult. PMID- 22085101 TI - A cost benefit analysis of the barbados family planning programme. AB - Abstract Of the Caribbean islands, Barbados has the lowest fertility level. The crude birth rate in 1970 was only 20.5 per 1,000, which is one of the lowest found in any country of similar economic development anywhere in the world. In 1960 the crude birth rate was much higher, at about 33.6 and for almost 40 years before that had fluctuated around a value of 33. Thus, a decline of about 40% has been achieved within the comparatively short period of a decade. The reasons for this rapid decline are of particular interest to all those concerned with population growth and economic development in the less developed areas. In Barbados, the importance of population control and the role of family planning was recognised early by the government and other civic agencies, and the Barbados Family Planning Association (BFPA), an autonomous national family planning agency, was established. Since its modest beginning in 1955 the BFPA has grown to be a major social institution, comprising 14 clinics situated in various localities throughout the island. In 1970, a full-time staff of 28 were providing services to an estimated 10,000 clients, about 20% of all women of reproductive age. Funds for the BFPA have come from local government with considerable assistance from international agencies. PMID- 22085102 TI - Population growth rates in perfect contraceptive populations. AB - Abstract Eventually, world population must cease to grow. In many countries attempts are made to decrease population growth by providing family planning services to all who want to prevent pregnancies. In this paper we use the concept 'perfect contraceptive population',(1) - a population in which no unwanted births occur - to derive estimates of the maximum contribution that prevention of unwanted births might make toward attaining a zero rate of natural increase in population. PMID- 22085103 TI - Family planning in Malta. AB - Abstract The crude birth rate has dropped dramatically in Malta(1) over the post-war period, from 36.0 per 1,000 population in 1948 to 17.1 in 1971. A drop of this magnitude is not uncommon(2) although it rarely occurs so fast. PMID- 22085106 TI - Errata. PMID- 22085107 TI - Errata. PMID- 22085108 TI - Allergic complications from orthopaedic joint implants: the role of delayed hypersensitivity to benzoyl peroxide in bone cement. AB - BACKGROUND: Orthopaedic implants and osteosynthesis materials are increasingly being used. Complications include mainly physical-mechanical problems and infections. Uncommonly, an allergic reaction towards an alloy metal or a bone cement component has been implicated. Potential bone cement allergens include acrylates, benzoyl peroxide, N,N-dimethyl-p-toluidine, and gentamicin. Typical symptoms are pain, swelling, inflammatory skin reactions, implant loosening, and fistula formation. OBJECTIVES: To report on 5 patients with complications from a knee or a shoulder joint implant in whom a relevant sensitization to benzoyl peroxide was shown. METHODS: Patch tests were performed with the European baseline series, an extended metal series, and a bone cement series. Patch tests with benzoyl peroxide were performed twice in all patients. A bone cement-free replacement was chosen in sensitized patients. RESULTS: In 4 patients sensitized to benzoyl peroxide, a bone cement-free replacement resulted in a considerable decrease or disappearance of pain and swelling, and complete clearing of cutaneous symptoms. CONCLUSIONS: Components of bone cement, such as benzoyl peroxide, may rarely cause allergic complications. However, because of the irritant potential of these substances, careful performance, reading and interpretation of the patch tests is required. PMID- 22085109 TI - Carbon consequences and agricultural implications of growing biofuel crops on marginal agricultural lands in China. AB - Using marginal agricultural lands to grow energy crops for biofuel feedstocks is a promising option to meet the biofuel needs in populous China without causing further food shortages or environmental problems. Here we quantify the effects of growing switchgrass and Miscanthus on Chinese marginal agricultural lands on biomass production and carbon emissions with a global-scale biogeochemical model. We find that the national net primary production (NPP) of these two biofuel crops are 622 and 1546 g C m(-2) yr(-1), respectively, whereas the NPP of food crops is about 600 g C m(-2) yr(-1) in China. The net carbon sink over the 47 Mha of marginal agricultural lands across China is 2.1 Tg C yr(-1) for switchgrass and 5.0 Tg C yr(-1) for Miscanthus. Soil organic carbon is estimated to be 10 kg C m( 2) in both biofuel ecosystems, which is equal to the soil carbon levels of grasslands in China. In order to reach the goal of 12.5 billion liters of bioethanol in 2020 using crop biomass as biofuel feedstocks, 7.9-8.0 Mha corn grain, 4.3-6.1 Mha switchgrass, or 1.4-2.0 Mha Miscanthus will be needed. Miscanthus has tremendous potential to meet future biofuel needs, and to benefit CO(2) mitigation in China. PMID- 22085110 TI - Tandem modular protein-based hydrogels constructed using a novel two-component approach. AB - Leucine zipper sequences have been widely used to engineer protein-based hydrogels for biomedical applications. Previously, we have used this method to engineer tandem modular protein-based hydrogels as a step toward developing extracellular matrix-mimetic hydrogels. However, the spontaneous self-association of leucine zipper sequences in solution has made it challenging to express and purify tandem modular proteins carrying leucine zipper under native conditions. To obviate this problem, here we report a novel two-component approach to engineer tandem modular protein-based hydrogels. This methodology makes use of two complementary leucine zipper sequences (CCE and CCK), which do not self associate but self-assemble into heterodimeric coiled-coils at neutral pH, as functional groups to drive the self-assembly of protein hydrogels. The two protein components are bifunctional and trifunctional tandem modular proteins carrying the leucine zipper functional groups. We found that the two proteins carrying CCE or CCK can be expressed and purified under native conditions with high yield. Upon mixing, the aqueous solution of the two proteins readily forms a transparent hydrogel. The resultant hydrogel can undergo reversible sol-gel transitions as a function of temperature, and shows much improved erosion properties. This method provides a new approach to tune the topology and physical properties of the protein hydrogels via genetic engineering, and opens the possibility to systematically explore the use of large native extracellular proteins to engineer extracellular matrix-mimetic hydrogels. PMID- 22085111 TI - Treatment of primary intraocular lymphoma with rituximab, high dose methotrexate, procarbazine, and vincristine chemotherapy, reduced whole-brain radiotherapy, and local ocular therapy. PMID- 22085112 TI - Tomentosones A and B, hexacyclic phloroglucinol derivatives from the Thai shrub Rhodomyrtus tomentosa. AB - Two phloroglucinols named tomentosones A and B (1 and 2) that each possess a novel hexacyclic ring system were isolated from the CH(2)Cl(2) extract of Rhodomyrtus tomentosa leaves. Their structures were elucidated from analyses of 2D NMR spectroscopic data. Tomentosone A inhibited the growth of chloroquine resistant and -sensitive strains of the malaria parasite Plasmodium falciparum, with IC(50) values of 1.49 MUM and 1.0 MUM, respectively, while tomentosone B was significantly less active. PMID- 22085113 TI - Cost analysis of store-and-forward telepsychiatry as a consultation model for primary care. AB - Store-and-forward telepsychiatry, or asynchronous telepsychiatry (ATP), which allows clinical data, including video to be collected to be reviewed at a later time by a specialist, has been described as a feasible alternative to real-time telepsychiatry, or synchronous telepsychiatry (STP), as a consultation model for primary care. In theory, ATP should be economically more cost-effective than STP due to the increased flexibility of patient data collection and the substitution of the time of specialists with that of lower-cost providers. The aim of this study was to conduct a retrospective cost-analysis comparing ATP with STP and traditional in-person psychiatric consultations in the primary care setting. One hundred and twenty five ATP consultations were performed and fixed and marginal costs were calculated for each model using inputs such as equipment costs, time spent by providers and support staff, and hourly salaries. The fixed costs were $7,000 and $20,000 for ATP and STP and marginal costs were $68.18, $107.50, and $96.36, respectively, for the three groups. STP was the most expensive of the three types of consultations. ATP became the most cost-effective of the three models beyond 249 consultations. The marginal cost savings of ATP were due to substitution of low-cost providers for specialists. ATP represents a potential disruptive healthcare process that could allow more affordable care to be delivered to a larger population of patients. A full accounting of ATP's efficiency will require further studies, including prospective cost-benefit analyses from the perspectives of the patient, provider, and society. PMID- 22085114 TI - A systematic review of the evidence base for telehospice. AB - Abstract The use of telehealth technologies to overcome the geographic distances in the delivery of hospice care has been termed telehospice. Although telehospice research has been conducted over the last 10 years, little is known about the comprehensive findings within the field. The purpose of this systematic article was to focus on available research and answer the question, What is the state of the evidence related to telehospice services? The article was limited to studies that had been published in the English language and indexed between January 1, 2000 and March 23, 2010. Indexed databases included PubMed and PsycINFO and contained specified key words. Only research published in peer review journals and reporting empirical data, rather than opinion or editorials, were included. A two-part scoring framework was modified and applied to assess the methodological rigor and pertinence of each study. Scoring criteria allowed the evaluation of both quantitative and qualitative methodologies. Twenty-six studies were identified with the search strategy. Although limited in number and in strength, studies have evaluated the use of a variety of technologies, attitudes toward use by providers and consumers, clinical outcomes, barriers, readiness, and cost. A small evidence base for telehospice has emerged over the last 10 years. Although the evidence is of medium strength, its pertinence is strong. The evidence base could be strengthened with randomized trials and additional clinical-outcome-focused research in larger randomized samples and in qualitative studies with better-described samples. PMID- 22085115 TI - Thiol-based posttranslational modifications in parasites. AB - SIGNIFICANCE: Cysteine residues of proteins participate in the catalysis of biochemical reactions, are crucial for redox reactions, and influence protein structure by the formation of disulfide bonds. Covalent posttranslational modifications (PTMs) of cysteine residues are important mediators of redox regulation and signaling by coupling protein activity to the cellular redox state, and moreover influence stability, function, and localization of proteins. A diverse group of protozoan and metazoan parasites are a major cause of diseases in humans, such as malaria, African trypanosomiasis, leishmaniasis, toxoplasmosis, filariasis, and schistosomiasis. RECENT ADVANCES: Human parasites undergo dramatic morphological and metabolic changes while they pass complex life cycles and adapt to changing environments in host and vector. These processes are in part regulated by PTMs of parasitic proteins. In human parasites, posttranslational cysteine modifications are involved in crucial cellular events such as signal transduction (S-glutathionylation and S-nitrosylation), redox regulation of proteins (S-glutathionylation and S-nitrosylation), protein trafficking and subcellular localization (palmitoylation and prenylation), as well as invasion into and egress from host cells (palmitoylation). This review focuses on the occurrence and mechanisms of these cysteine modifications in parasites. CRITICAL ISSUES: Studies on cysteine modifications in human parasites are so far largely based on in vitro experiments. FUTURE DIRECTIONS: The in vivo regulation of cysteine modifications and their role in parasite development will be of great interest in order to understand redox signaling in parasites. PMID- 22085118 TI - Early management and long-term outcomes in primary vesico-ureteric reflux. AB - What's known on the subject? and What does the study add? Despite evolving understanding of pathogenesis and natural history, controversy exists regarding management of childhood vesicoureteric reflux. Surgical correction of the reflux itself may reduce risk of upper tract complications in some but may not in itself constitute appropriate management of lower tract morbidity in many. This review examines the evidence for early management and long term outcomes in primary vesicoureteric reflux. Primary vesico-ureteric reflux is a common condition in childhood associated with bladder dysfunction and an increased risk of urinary tract infection. Recent evidence indicates a lower tract functional abnormality in its pathogenesis. Whilst spontaneous resolution will occur in many, some patients will go on to develop complications in adulthood including reflux nephropathy, hypertension, urinary tract infection, bladder dysfunction and complications of pregnancy. An evolving understanding of the natural history has seen radical changes in management. Evidence for management of the child with primary vesico-ureteric reflux is reviewed with a focus on the implications on long-term outcomes in adulthood. PMID- 22085119 TI - Urolithiasis--medical therapies. AB - This review paper provides a summary of medical therapies available for urolithiasis. The summary includes general medical advice, prophylactic medications, dissolution therapy and medical expulsion therapy. The paper is designed to provide a management strategy for all physicians who treat urolithiasis, from general practitioners, to emergency physicians, to urologists. OBJECTIVE: * To provide an up to date review of the literature in relation to the medical management of stone disease. This will encompass prophylaxis, dissolution therapy and medical expulsion therapy. PATIENTS AND METHODS: * First-time stone formers do not regularly have a full urine and electrolyte evaluation due to the low incidence of a reversible metabolic cause. * However, stone disease is common and over a lifetime urolithiasis can affect up to 10-15% of the population. RESULTS: * Medical management of stone disease encompasses preventative measures, medical dissolution and medical expulsion therapy. CONCLUSIONS: * Recurrent stone formers should have dietary optimization to decrease the risk of further stones. * Furthermore, the correct use of prophylactic and therapeutic medications can decrease the morbidity associated with ureteric calculi. PMID- 22085120 TI - Penile lichen sclerosus (balanitis xerotica obliterans). AB - What's known on the subject? and What does the study add? The clinical presentation and complications of lichen sclerosus are well known. What is less well known is the true incidence of the condition. The published figures are all based on attendance at general medical clinics or specialist clinics, but it is likely that the true incidence is much higher than this reported incidence as many men will not present to the doctor for treatment. The other uncertainty is the relationship of lichen sclerosus to the subsequent development of cancer of the penis. As pointed out in the paper, it is likely that between 4% and 8% of men with this condition will develop squamous cell cancer of the penis. However, it is unclear if lichen sclerosus itself causes the development of squamous cell cancer or if it is due to coexistent infection with human papillomavirus. This review provides a concise summary of the clinical and pathological features of the disease and describes its current medical and surgical treatment. It brings together a number of papers which have addressed the association of lichen sclerosus with squamous cell carcinoma of the penis and shows that the likely incidence of carcinoma is approximately 4-8% in men with this condition. SUMMARY: Penile lichen sclerosus, also known as balanitis xerotica obliterans, is a chronic inflammatory condition of the penis which can occur at all ages. The inflammation leads to the formation of white plaques most commonly on the foreskin or penis, and can lead to inability to retract the foreskin or blockage to the flow of urine. Cancer may occur rarely. Penile lichen sclerosus is a progressive, sclerosing, inflammatory dermatosis of the glans penis and foreskin which is of uncertain aetiology. Recent studies have shown a link between lichen sclerosus and squamous cell carcinoma of the penis. In this review, we discuss the clinical presentation, pathology and current approach to treatment of this condition. PMID- 22085121 TI - Urethral diverticula in females. AB - What's known on the subject? and What does the study add? This is a review of urethral diverticula in females. In addition to modes of presentation, differential diagnosis, complications and surgical management, the increasingly recognised value of computerised axial imaging, especially with MRI, is highlighted. Urethral diverticula are rare but under-diagnosed entities that may cause a variety of urinary and pelvic symptoms in women. They are best demonstrated by magnetic resonance imaging and micturating cysto-urethrography prior to transvaginal surgical excision. Although unlikely, the possibility of malignant transformation should not be forgotten. PMID- 22085122 TI - Outlet obstruction after sling surgery. AB - What's known on the subject? and What does the study add? This article provides a current update on the risk factors, clinical features, and diagnosis on obstruction after female stress incontinence surgery using the mid-urethral synthetic sling. Particular attention has been paid to identify the patient at risk for developing voiding difficulty post-sling surgery, as well as the utility of urodynamics and various imaging modalities, especially translabial ultrasound, in the diagnostic process. Urethral obstruction is not an uncommon complication after sling surgery for female stress urinary incontinence (SUI). This paper focuses on this complication in the context of the mid-urethral synthetic sling, which is now the predominate surgical option used by many surgeons in the treatment of female SUI. The epidemiology and risk factors predisposing to sling obstruction is reviewed, followed by a description of clinical features used in supporting the diagnosis. The use of urodynamics in conjunction with translabial ultrasound as a novel approach to assess the position of the sling and its relation to the urethra is explained. This is particularly important in the understanding of why the sling obstructs from an anatomical standpoint. The paper concludes with a brief overview on treatment options. PMID- 22085123 TI - Evolution of stone management in Australia. AB - What's known on the subject? and What does the study add? There is very little contemporary data regarding stone management in Australia. This study assesses the impact of technological advances on stone management practises, and raises questions as to why there is an increasing rate of intervention for stone disease in Australia. Knowledge of management trends as demonstrated in this paper give individual surgeons a guideline for contemporary practise in this country. OBJECTIVE: * To examine trends in the operative management of upper urinary tract stone disease in Australia over the past 15 years. MATERIALS AND METHODS: * The Medicare Australia and Australian Institute of Health and Welfare databases were used to determine the annual number of renal colic presentations and procedural interventions undertaken for stone disease. RESULTS: * In Australia over the past 15 years, the annual number of procedural interventions for upper urinary tract stones has increased, primarily due to the rising number of endoscopic procedures performed. * During this period, shock wave lithotripsy numbers have remained steady whilst open and percutaneous procedures have been in decline. CONCLUSION: * The introduction of and subsequent preference for less invasive techniques has changed the management pathway of patients presenting with stone disease in Australia. * Further studies are necessary to determine whether this escalation in endoscopic procedures is due to an increase in the incidence of stone disease, earlier detection, a lower intervention threshold or a higher retreatment rate. PMID- 22085124 TI - Repeated radiological radiation exposure in patients undergoing surgery for urinary tract stone disease in Victoria, Australia. AB - What's known on the subject? and What does the study add? Radiation exposure is a cause of cancer. Increasing use of CT scans has increased patient exposure to ionizing radiation which may increase long-term risk of cancer. Not all scans performed may be medically necessary. Up to 30% of patients presenting with renal/ureteric colic have been estimated to receive too much radiation. At least 30% of patients attending for stone surgery have exceeded the recommended annual radiation dosage. Many Australian radiology providers do not routinely record CT radiation dose. Radiation dose varies widely between individual patients and between radiology providers. Image intensifiers may be an additional significant source of radiation exposure. Implementing guidelines and informing patients of their cumulative radiation exposure should reduce exposure and risk. SUMMARY: At least 44% of a group of patients undergoing stone operations have been exposed to high levels of radiation, mostly from repeated CT scans, over a short period with possible increased risk of developing cancer. We suggest ways in which that risk can be reduced. OBJECTIVE: * To assess radiation exposure in patients attending for surgery for urinary tract stones. PATIENTS AND METHODS: * Fifty-eight consecutive patients attending for stone surgery were asked to provide their radiological imaging over the preceding year. * Radiation dosage was recorded where available. Individual radiology providers were contacted to provide additional data. RESULTS: * The median number of radiological investigations was six (range 2-15). * Patients had attended 12 different providers on 22 sites. Only three providers routinely recorded computed tomography (CT) radiation dose. * Up to 26 patients (44%) were subjected to at least 50 mGy radiation in the course of their treatment with at least eight (13.8%) receiving over 100 mGy from CT scans alone. * CT and image intensifier radiation dose varied considerably between providers even for the same patients. CONCLUSIONS: * Many patients with urinary tract stones are subjected to relatively high doses of radiation in the course of their investigation and treatment. This may have later malignant consequences. * Many providers in Australia are not recording radiation dose and patients seem to have many unnecessary scans. * Suggestions on improved management are made which could significantly reduce radiation exposure. PMID- 22085125 TI - Complete resolution of urinary bladder condyloma acuminatum following definitive chemoradiotherapy for anal cancer. AB - What's known on the subject? and What does the study add? Condyloma acuminatum of the bladder is a rare affliction and as such its ideal management is unknown. This manuscript describes curative treatment of severe disease with external beam radiotherapy concurrent with low dose chemotherapy, an approach which has not previously been utilised. OBJECTIVES: * To report the first occurrence of complete and sustained resolution of symptomatic condyloma acuminatum of the bladder with chemoradiotherapy. * To describe the relevant patient details, imaging findings and chemoradiation treatment. PATIENT AND METHOD: * A 54-year old female with extensive condyloma acuminatum of the bladder and a long history of human papilloma virus related anogenital disease was diagnosed with anal squamous cell carcinoma. * Cystectomy for the bladder disease was delayed whilst chemoradiotherapy was administered for the anal cancer. RESULTS: * There was complete resolution of bladder disease at follow-up which has negated the need for cystectomy with its associated morbidity. * Condyloma acuminatum has not recurred in 4 years of follow-up. CONCLUSION: * This is the first published report to our knowledge of the successful treatment of condyloma acuminatum of the bladder with chemoradiotherapy. * The individual contributions of radiotherapy vs chemotherapy cannot be discerned. PMID- 22085126 TI - Male flexible cystoscopy: does waiting after insertion of topical anaesthetic lubricant improve patient comfort? AB - What's known on the subject? and What does the study add? Flexible cystoscopy is commonly performed. Several studies show that topical anaesthetic lubricant reduces patient discomfort, particularly with long lubricant retention times (15 25 min). No studies have specifically addressed whether a short, clinically manageable retention time provides any benefit over immediate cystoscopy. Our study demonstrates that delay by a 3-min interval provides no benefit to patients and a more expedient approach can be justified without compromising patient comfort. LAY-TERM SUMMARY: This prospective comparative trial randomizes 50 men to undergo flexible cystoscopy with insertion of local anaesthetic lubricant either immediately prior to cystoscope insertion or after a 3-min interval. Patients then report discomfort on a visual analogue scale. We show that there is no benefit to delay and therefore a more expedient approach can be justified. OBJECTIVE: * To determine whether a short, clinically manageable time delay between lubrication with topical local anaesthetic and insertion of the flexible cystoscope, vs immediate insertion, reduces discomfort in male patients. PATIENTS AND METHODS: * This was a prospective comparative trial. * Male patients undergoing simple flexible cystoscopy were randomized to undergo cystoscope insertion either immediately after lubrication with topical lignocaine gel or after a 3-min delay. * Patient-reported pain of the procedure was recorded on a visual analogue scale and data were statistically analysed. RESULTS: * Fifty male patients were randomized to cystoscope insertion either immediately following lubrication or after a 3-min delay. * Mean pain score in the immediate insertion group was 11.94 mm (95% confidence interval [CI] 7.53-16.36) compared with 10.52 mm (95% CI 6.24-14.80) in the 3-min delay group. * The mean difference between the two groups was 1.42 mm (95% CI -4.57 to 7.41, P= 0.64). CONCLUSION: * Findings show that patient comfort is similar between the two groups and therefore there is no benefit in delaying insertion by a 3-min interval. * Flexible cystoscopy is a well tolerated outpatient procedure. PMID- 22085127 TI - A retrospective study to assess the morbidity associated with transurethral prostatectomy in patients on antiplatelet or anticoagulant drugs. AB - What's known on the subject? and What does the study add? There is controversy over the use of anti-platelet and anti-coagulant drugs in men undergoing TURP with contradictory evidence on the effect of the drugs on bleeding following the operation, particularly for aspirin. If anti-platelet or anti-coagulant drugs are not stopped for TURP, there is an unacceptable burden of bleeding. If the drugs are stopped there is an unacceptable rate of cardiovascular events. OBJECTIVE: * To determine the morbidity associated with perioperative management of antiplatelet (AP) or anticoagulant (AC) medication and transurethral prostatectomy. PATIENTS AND METHODS: * A retrospective review was performed on 163 consecutive patients undergoing transurethural prostatectomy. * Patients were grouped according to the perioperative management of AP and AC medications: control patients not prescribed any AP/AC drugs (group 1), those on AP/AC who had ceased them perioperatively (group 2) and those whose AP/AC were continued (group 3). * Warfarin was withheld perioperatively for all patients. * Morbidity associated with increased blood loss and cardiovascular or cerebrovascular events was recorded and differences were analysed with SPSS version 16 software. RESULTS: * There was a statistically significant increase in bleeding-associated morbidity in group 2 (13/65) and group 3 (6/7) compared with the controls (9/91) (P < 0.01). * Cardiovascular and cerebrovascular events were only seen in group 2 (6/65), statistically significantly higher than the event rate in the other groups (P <= 0.01). * All cardiovascular or cerebrovascular events occurred in patients prescribed these medications for secondary prevention. CONCLUSION: * Patients taking AP or AC medications have a higher rate of perioperative bleeding compared with those who are not taking any. * However, for patients prescribed AP or AC medication for secondary prevention, withholding these medications results in an increased rate of cardiovascular and cerebrovascular complications. * Careful consideration of the risks and other management options should be undertaken before performing transurethural prostatectomy in this high risk group of patients. PMID- 22085128 TI - We should cease offering turp in favour of alternative surgery options for anticoagulated patients. PMID- 22085130 TI - Comparative analysis of three risk assessment tools in Australian patients with prostate cancer. PMID- 22085129 TI - Comparative analysis of three risk assessment tools in Australian patients with prostate cancer. AB - What's known on the subject? and What does the study add? Prognostic tools, such as the Cancer of the Prostate Risk Assessment (CAPRA) score and the 1998 Kattan and 2006 Stephenson nomograms, predicting biochemical recurrence after radical prostatectomy are widely used for treatment decision making and counselling patients. However, tools derived in certain cohorts tend to perform less well when they are applied to populations that are dissimilar in terms of population or disease characteristics, health systems or treatment practices. Some of the loss in accuracy of a prognostic tool is a consequence of unknown factors and hence the performance of a tool when applied to a different population is unknown and largely unpredictable. This study validates these widely used tools in South Australian patients treated at three public hospitals. All three tools discriminated well according to risk of recurrence in these patients. However, when compared against observed rates of recurrence, it was found that predictions of recurrence varied widely between the three tools, suggesting that their use in counselling patients on such risk may not be appropriate. Interestingly, the oldest of the three tools (Kattan 1998) was the best predictor of absolute risk of recurrence. In the paper, this is linked to later adoption of updated Gleason grading, among other factors. SUMMARY: In many countries, prognostic tools, which draw on the experience of thousands of patients with cancer, are used to predict cancer outcomes, but accuracy varies. This paper compares the accuracy of three widely used tools predicting prostate cancer recurrence after surgery in Australian patients. The results show that all tools were good at predicting which patients were most likely to experience recurrence and which were least. However, prediction of absolute risk varied and the oldest tool was the most accurate. OBJECTIVE: * To compare performance of the CAPRA score and two commonly used risk assessment nomograms, the 1998 Kattan and the 2006 Stephenson, in an untested Australian cohort. PATIENTS AND METHODS: * We present data on 635 men from the South Australian Prostate Cancer Clinical Outcomes Database who underwent radical prostatectomy between January 1996 and May 2009 and had all required variables for predicting biochemical recurrence (BCR). * BCR was defined as prostate-specific antigen >= 0.2 ng/mL or secondary treatment for a rising prostate-specific antigen. * Accuracy was evaluated using Harrell's concordance index, plotting calibration curves, and constructing decision analysis curves. RESULTS: * Concordance indices were high for all three tools: 0.791, 0.787 and 0.744 for the 2006 Stephenson nomogram, CAPRA score and 1998 Kattan nomogram respectively. * At 3 years, calibration of the tools (agreement between predicted and observed BCR-free probability) was close to ideal for the 1998 Kattan nomogram, whereas the 2006 Stephenson model underestimated and the CAPRA model overestimated BCR-free probability. * The 1998 Kattan and 2005 CAPRA tools performed better than the 2006 Stephenson nomogram across a wide range of threshold probabilities using decision curve analysis. CONCLUSION: * All three tools discriminate between patients' risk effectively. * Absolute estimates of risk are likely to vary widely between tools, however, suggesting that models should be validated and, if necessary, recalibrated in the population to which they will be applied. * Recent development does not mean a nomogram is more accurate for use in a particular population. PMID- 22085131 TI - Patients' perceptions of surgical registrars' training in the private hospital setting. AB - What's known on the subject? and What does the study add? The Australian private health sector is increasingly being recognised as an opportunity for advanced surgical training. Little is known about what the patients think of urology training in the private sector. Patients perceptions on the place of urology registrars in the Australian private sector are assessed for the first time. We can confirm that there appears to be acceptance of urology training in the private sector. OBJECTIVE: * To determine the acceptance of surgical trainees in a private hospital setting. METHOD: * This was an ethics approved prospective study using a written survey. * A total of 177 consecutive patients presenting for private consultation were recruited. A self-administered written survey was completed by each patient in the waiting room prior to consultation. RESULTS: * Only 36.8% of subjects (confidence interval 29.6-44.1) initially understood the term registrar which significantly increased to 75% (confidence interval 68.4 81.6, P < 0.05) after reading explanatory notes. * Perceived differences between private and public hospitals were choice of surgeon (28%), waiting times for an operation (28%), standard of care (17%), cost (16%) and waiting times for an appointment (11%). * Patients' acceptance of registrar involvement with either a small part of an operation, a large part of an operation, the whole operation and assistance only were 34%, 16%, 13% and 37%. CONCLUSIONS: * Patients have a poor understanding of the term registrar. * Acceptance of registrars in private hospitals is increased if consultant involvement is emphasized. * Surgical assistance and performance of minor parts of surgery by trainees is well accepted. PMID- 22085132 TI - 'One stop' haematuria clinic in Fremantle Hospital, Western Australia: a report of the first 500 patients. AB - What's known on the subject? and What does the study add? Haematuria is a symptom of urologic cancer particularly bladder cancer and timely diagnosis can prevent disease from progression to a more advanced or incurable stage. The 'One Stop' Haematuria clinic is the first rapid assessment clinic for haematuria in a public hospital in Western Australia. The results from this study have confirmed that it is an efficient and effective model in the streamlined care of patients with haematuria and provides evidence to support a more widespread adoption of this model of care. OBJECTIVE: * To report the prospective outcomes and clinic process for the first 500 patients at a new 'one stop' Haematuria Clinic (OSHC) in a Western Australian public hospital. PATIENTS AND METHODS: * The first 500 patients who attended the weekly OSHC between May 2008 and February 2011 were included in this paper. * Patients with haematuria were referred by various specialties. Gender, age, outcomes following OSHC attendance, diagnoses and wait times were recorded. RESULTS: * In all, 311 males and 189 females presented to the clinic with visible haematuria (296 cases) and microscopic haematuria (204 cases). * Sixty-six new cancers (13.2%) were diagnosed, 63 urological and three non-urological. * Fifty-one patients (10.2%) were diagnosed with transitional cell carcinoma of the bladder. Further breakdown of staging for bladder transitional cell carcinoma diagnoses were stage Ta (23 patients), stage T1 (21 patients) and stage 2-4 (seven patients). * Sixty-nine patients (13.8%) were diagnosed with urological pathologies requiring surgery. Thirty-four patients (6.8%) were followed up by the nurse practitioner or continence advisors. In all, 61.2% of patients were discharged after a single visit to the OSHC. * Excluding those requiring surgery only 3.4% patients required further urologist follow-up. CONCLUSION: * The results have demonstrated that the first OSHC in a public Western Australian hospital is an efficient and effective model for the streamlined care of patients with haematuria. * We encourage that similar models are adopted in other public hospitals in the region. PMID- 22085133 TI - Prostate cancer incidence in Australia correlates inversely with solar radiation. AB - What's known on the subject? and What does the study add? Increased sun exposure and blood levels of vitamin D have been postulated to be protective against prostate cancer. This is controversial. We investigated the relationship between prostate cancer incidence and solar radiation in non-urban Australia, and found a lower incidence in regions receiving more sunlight. In landmark ecological studies, prostate cancer mortality rates have been shown to be inversely related to ultraviolet radiation exposure. Investigators have hypothesised that ultraviolet radiation acts by increasing production of vitamin D, which inhibits prostate cancer cells in vitro. However, analyses of serum levels of vitamin D in men with prostate cancer have failed to support this hypothesis. This study has found an inverse correlation between solar radiation and prostate cancer incidence in Australia. Our population (previously unstudied) represents the third group to exhibit this correlation. Significantly, the demographics and climate of Australia differ markedly from those of previous studies conducted on men in the United Kingdom and the United States. OBJECTIVE: * To ascertain if prostate cancer incidence rates correlate with solar radiation among non-urban populations of men in Australia. PATIENTS AND METHODS: * Local government areas from each state and territory were selected using explicit criteria. Urban areas were excluded from analysis. * For each local government area, prostate cancer incidence rates and averaged long-term solar radiation were obtained. * The strength of the association between prostate cancer incidence and solar radiation was determined. RESULTS: * Among 70 local government areas of Australia, age standardized prostate cancer incidence rates for the period 1998-2007 correlated inversely with daily solar radiation averaged over the last two decades. CONCLUSION: * There exists an association between less solar radiation and higher prostate cancer incidence in Australia. PMID- 22085134 TI - Reporting a unique example of electronic bistability observed in the form of valence tautomerism with a copper(II) helicate of a redox-active nitrogenous heterocyclic ligand. AB - Valence tautomeric compounds involving nondixolene-type ligands are rare. The triple-helicate copper(II) complex [Cu(II)(2)(L)(3)](ClO(4))(4).3CH(3)CN (1) containing a redox-active N-heterocyclic ligand (L) has been prepared and displays VT equilibrium in solution, as established by electronic spectroscopy, electron paramagnetic resonance spectroscopy, and cyclic and differential pulse voltammetry carried out at variable temperatures. The process involves intramolecular transfer of an electron from one of the L ligands to a copper(II) center, leading to the oxidation of L to an L(*+) radical with concomitant reduction of the Cu(II) center to Cu(I), as shown by the equilibrium [Cu(II)Cu(I)L(*+)L(2)](4+) ? [Cu(II)(2)L(3)](4+). PMID- 22085136 TI - Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans. AB - Intermittent low-dose treatment with parathyroid hormone (PTH) analogues has become widely used in the treatment of severe osteoporosis. During normal physiological conditions, PTH stimulates both bone formation and resorption, and in patients with primary hyperparathyroidism, bone loss is frequent. However, development of the biochemical measurement of PTH in the 1980s led us to understand the regulation of PTH secretion and calcium metabolism which subsequently paved the way for the use of PTH as an anabolic treatment of osteoporosis as, when given intermittently, it has strong anabolic effects in bone. This could not have taken place without the basic understanding achieved by the biochemical measurements of PTH. The stimulatory effects of PTH on bone formation have been explained by the so-called 'anabolic window', which means that during PTH treatment, bone formation is in excess over bone resorption during the first 6-18 months. This is due to the following: (1) PTH up-regulates c-fos expression in bone cells, (2) IGF is essential for PTH's anabolic effect, (3) bone lining cells are driven to differentiate into osteoblasts, (4) mesenchymal stem cells adhesion to bone surface is enhanced, (5) PTH has a direct antiapoptotic effect on osteoblasts and (6) when PTH interferes with remodelling, the osteoblasts over-compensate, and (7) PTH also decreases sclerostin levels, thereby removing inhibition of Wnt signalling which is required for PTH's anabolic actions. Thus, the net formative effect of PTH given in intermittent treatment emerges through a complex network of pathways. In summary, the effects of PTH on bone turnover are dependent on the mode and dose of administration and studies investigating the mechanisms underlying this effect are reviewed in this article. PMID- 22085137 TI - Novel phenoxyalkylcarboxylic acid derivatives as hypolipidaemic agents. AB - Novel phenoxyalkylcarboxylic acid derivatives based on the natural scaffolds, flavonoids, or resveratrol were designed, synthesized, and evaluated for hypolipidaemic activity. Among the compounds, 30b lowered the triglycerides by 48.5% (P < 0.05) and total cholesterol by 44.2% (P < 0.05), respectively, and was more effective than the reference drug fenofibric acid in a Triton WR-1339 induced hyperlipidaemic mice model orally (300 mg/kg body weight). 30b also showed 59.4% triglycerides lowering in an alloxan-induced diabetic mice model orally (150 mg/kg body weight). Receptor docking studies revealed that compound 30b could interact with the amino acid residues in the ligand-binding domain essential for the activation of the PPARalpha. The results indicate that resveratrol should be a better scaffold to derive a new class of hypolipidaemic agents in comparison with a flavonoid scaffold. PMID- 22085135 TI - Reduced fronto-cerebellar functional connectivity in chronic alcoholic patients. AB - BACKGROUND: Alcohol dependence is associated with neurocognitive deficits related to neuropathological changes in structure, metabolism, and function of the brain. Impairments of motor functioning in alcoholics have been attributed to well characterized neuropathological brain abnormalities in cerebellum. METHODS: Using functional magnetic resonance imaging (fMRI), we studied in vivo the functional connectivity between cerebellar and cortical brain regions. Participants were 10 uncomplicated chronic alcoholic patients studied after 5 to 7 days of abstinence when signs of withdrawal had abated and 10 matched healthy controls. We focused on regions of prefrontal, frontal, temporal, and parietal cortex that exhibited an fMRI response associated with nondominant hand finger tapping in the patients but not in the controls. We predicted that fronto-cerebellar functional connectivity would be diminished in alcoholics compared with controls. RESULTS: Functional connectivity in a circuit involving premotor areas (Brodmann Area 6) and Lobule VI of the superior cerebellum was reduced in the patients compared with the controls. Functional connectivity was also reduced in a circuit involving prefrontal cortex (Brodmann Area 9) and Lobule VIII of the inferior cerebellum. Reductions in connectivity were specific to fronto-cerebellar circuits and were not found in other regions examined. CONCLUSIONS: Our findings show a pattern in recently abstinent alcoholic patients of specific deficits in functional connectivity and recruitment of additional brain regions for the performance of a simple finger-tapping task. A small sample, differences in smoking, and a brief abstinence period preclude definitive conclusions, but this pattern of diminished fronto-cerebellar functional connectivity is highly compatible with the characteristic neuropathological lesions documented in alcoholics and may reflect brain dysfunction associated with alcoholism. PMID- 22085138 TI - Synthesis, antibacterial, antielastase, antiurease and antioxidant activities of new methoxy substitued bis-1,2,4-triazole derivatives. AB - The methoxy substitued two novel bis triazole-schiff bases (6 a-b) were synthesized with 4-amino-3,5-diethyl-4H-1,2,4-triazole and various bis-aldehydes. Their amine derivatives prepared by reduced with NaBH(4) (5 a-b). The obtained products 6 a-b and 7 a-b were identified by FT-IR, (1)H-NMR, (13)C-NMR. The bis triazole-schiff bases and amine derivatives were tested for antimicrobial activity using the agar diffusion technique against 11 bacteria. The synthesized compounds (6 a-b and 7 a-b) were screened for their antielastase, antiurease and antioxidant activities. The resuts showed that the synthesized compounds (6 a-b and 7 a-b) had effective antielastase and antiurease activities. PMID- 22085139 TI - Synthesis and evaluation of substrate analogue inhibitors of trypanothione reductase. AB - Trypanothione reductase (TR) is found in the trypanosomatid parasites, where it catalyses the NADPH-dependent reduction of the glutathione analogue, trypanothione, and is a key player in the parasite's defenses against oxidative stress. TR is a promising target for the development of antitrypanosomal drugs; here, we report our synthesis and evaluation of compounds 3-5 as low micromolar Trypanosoma cruzi TR inhibitors. Although 4 and 5 were designed as potential irreversible inhibitors, these compounds, as well as 3, displayed reversible competitive inhibition. Compound 3 proved to be the most potent inhibitor, with a K(i) = 2 uM. PMID- 22085140 TI - Selenium-catalyzed regioselective cyclization of unsaturated carboxylic acids using hypervalent iodine oxidants. AB - A new and convenient selenium-catalyzed regioselective cyclization of gamma,delta unsaturated carboxylic acids to the corresponding 3,6-dihydro-2H-pyran-2-ones is described. The cyclization products have been obtained in good to excellent yields using diphenyl diselenide as a catalyst and [bis(trifluoroacetoxy)iodo]benzene as a stoichiometric oxidant. PMID- 22085141 TI - Intravenous immunoglobulin to treat severe atopic dermatitis in children: a case series. AB - Severe cases of atopic dermatitis (AD) may require systemic immunosuppression to achieve disease control. Unfortunately, some cases continue to be refractory to management or develop unacceptable adverse effects. There are limited reports of the use of intravenous immunoglobulin (IVIg) in the treatment of severe AD, but results are inconsistent. In a retrospective study, we report 10 children with severe AD refractory to systemic immunosuppression and maximal topical therapy who were treated using IVIg. The children received monthly IVIg for an average of 24 months. This resulted in a significant improvement in symptoms, with fewer infection-related exacerbations and hospitalizations, allowing systemic immunosuppression to be tapered. The effect was associated with a significant decrease in serum immunoglobulin E and was sustained after cessation of IVIg in 50% of cases. No significant side effects attributable to the IVIg infusions were noted. In this cohort of children with severe AD and recurrent cutaneous infections, IVIg provided an effective treatment with minimal side effects and significant benefits in school attendance and quality of life. PMID- 22085142 TI - The timing of Spanish marriages a socio-statistical study. AB - Abstract A sample survey of 2,012 married and single women aged 18-59 in Madrid was in part focused on causes of late marriage, which has for a long time been characteristic of Spain. It was found that age at marriage was not related to a variety of socio-economic measures, to parental restrictions on courtship, nor to birth order or number of siblings. Direct economic motivations appear to have affected length of courtship but scarcely age at marriage. Ages at marriage differ in different areas of Madrid, even when key demographic and social variables are controlled; and evidence from a sub-sample of interviews suggests that it may be a characteristic of different families. Along with clear evidence of normative patterns supporting long courtships and late marriages, such data point to the potential importance of sociological variables, and to the need for similar research on determinants of men's ages at marriage. PMID- 22085143 TI - Complementarity of work and fertility among young American mothers. AB - Abstract In this paper information about cohorts of young women in the National Longitudinal Survey of Work Experience is used to examine the extent to which women maintain a continuity of work attachment during their early years of childbearing, the years when traditionally they were most likely to withdraw from the work force. The results indicate that women who maintain closer ties to the work force immediately before and after their first birth are also more likely to be employed in 1978 - between five and ten years after their first birth - independently of intervening fertility events and other labour supply factors considered to be important predictors of work. The notion that work and fertility are increasingly becoming complementary activities for American women is supported by these data. PMID- 22085144 TI - The timing of entry into motherhood in Asia: A comparative perspective. AB - Abstract This paper examines the determinants of age at first birth from an explicitly comparative perspective in the following Asian societies: Hong Kong, Indonesia, Malaysia, the Philippines, South Korea, Sri Lanka, Taiwan and Thailand. The key structural variables have the same (or similar) effects in each of the groups examined. Education through primary school and beyond has a strong delaying effect on age at first birth in all eight populations. Difference of rural-urban origin does not affect the timing of motherhood in any of these societies. We also find a remarkably strong effect of shared cultural heritage. All the Confucian groups tend to behave similarly, as do the Muslim and Hindu groups. PMID- 22085145 TI - An analysis of indirect mortality estimation. AB - Abstract In this paper the robustness of Brass's child-survivorship indirect mortality estimation technique is investigated. An analytical method is developed for studying the error or bias caused in indirect mortality estimates by poor data, badly chosen model functions, and specific demographic assumptions that are often violated in practice. The resulting analytical expressions give insight into the rationale of indirect methods, the conditions under which they are robust, and the magnitude of errors that occur when specific assumptions are violated. PMID- 22085146 TI - On the estimation of the distribution of desired family size for a synthetic cohort. AB - Abstract Current procedures for the estimation of the desired family size distribution from parity-specific data on proportions of women wanting another child are shown to be biased. A new procedure is proposed. This procedure is based on the underlying relationship between parity and desired family size as measured by the extent to which members of the population implement their fertility preferences. Numerical examples are given. PMID- 22085150 TI - Correlates of the trend of cesarean section rates in twin pregnancies. AB - OBJECTIVE: To examine the population-based trend for cesarean births in twin pregnancies for the last 13 years in Slovenia, and to find correlates for this trend. METHODS: We evaluated data from the Slovenian national perinatal information system (NPIS) of all twin pairs born at >=24 weeks during the period 1997-2009 (n=3916 pairs). RESULTS: We noted a significant and steady increase of about 1.1% cesarean births/year, concomitant with significant increased birth rates at 34-36 weeks, but with a significant decrease over time in neonatal mortality. These trends were neither associated with any particular maternal characteristic nor with increased neonatal morbidity. CONCLUSIONS: An association exists between an increased cesarean birth rate, increased preterm births at 33 36 weeks and concomitant significantly reduced neonatal mortality in twins. PMID- 22085151 TI - Total serum bilirubin level in umbilical cord blood and respiratory distress syndrome in very low birth weight infants. AB - AIMS: To explore the association between total serum bilirubin (TSB) level in umbilical cord blood (UCB) and the occurrence and/or severity of respiratory distress syndrome (RDS) in very low birth weight (VLBW) infants. METHODS: We performed a prospective study of 579 VLBW infants. The mean TSB level in UCB (1.8 mg/dL) was used to divide the cohort into two groups: neonates with levels <1.8 mg/dL and those with levels >1.8 mg/dL. Demographic and clinical characteristics of the 2 groups, including diagnosis of RDS, need for ventilation, peak fraction of inspired oxygen (FiO2), oxygenation index (OI), and duration of respiratory support, were compared. RESULTS: Three hundred and twenty-four infants were included in the low-TSB group and 255 infants were included in the high-TSB group. RDS was less frequent in the high TSB group than in the low one (46.3% vs. 56.6%, P=0.01). A negative association between TSB level in UCB and the occurrence of RDS [odds ratio (OR)=0.620; 95% confidence interval (CI) 0.440 0.873, P=0.006] was observed. However, lower TSB in UCB was not associated with the maximum FiO2, OI, or duration of mechanical ventilation. CONCLUSIONS: VLBW infants with low TSB levels in UCB were more likely to develop RDS. However, in conjunction with surfactant replacement therapy, no correlation was found between TSB levels in UCB and the severity of RDS. The negative association between high TSB in UCB and RDS warrants further investigation. PMID- 22085152 TI - Prediction of imminent preterm delivery in women with preterm premature rupture of membranes. AB - AIMS: To develop a model based on non-invasive clinical parameters to predict the probability of imminent preterm delivery (delivery within 48 h) in women with preterm premature rupture of membranes (PPROM), and to determine if additional invasive test results improve the prediction of imminent delivery based on the non-invasive model. METHODS: Transvaginal ultrasonographic assessment of cervical length was performed and maternal serum C-reactive protein (CRP) and white blood cell (WBC) count were determined immediately after amniocentesis in 102 consecutive women with PPROM at 23-33+6 weeks. Amniotic fluid (AF) obtained by amniocentesis was cultured and interleukin-6 (IL-6) levels and WBC counts were determined. RESULTS: Serum CRP, cervical length, and gestational age were chosen for the non-invasive model (model 1), which has an area under the curve (AUC) of 0.804. When adding AF IL-6 as an invasive marker to the non-invasive model, serum CRP was excluded from the final model (model 2) as not significant, whereas AF IL 6, cervical length, and gestational age remained in model 2. No significant difference in AUC was found between models 1 and 2. CONCLUSIONS: The non-invasive model based on cervical length, gestational age, and serum CRP is highly predictive of imminent delivery in women with PPROM. However, invasive test results did not add predictive information to the non-invasive model in this setting. PMID- 22085153 TI - Fetal and neonatal outcome in patients with anterior abdominal wall defects (gastroschisis and omphalocele). AB - Fetuses with gastroschisis and omphalocele frequently show intrauterine growth restriction (IUGR). The aim of our study was to evaluate the intrauterine course of IUGR and the neonatal outcome in a large patient collective. We retrospectively included all euploid fetuses with gastroschisis and omphalocele between 2001 and 2009 in a single tertiary center. Patients' characteristics, serial ultrasound examinations and neonatal outcomes were evaluated. From 39 fetuses (28 gastroschisis, 11 omphalocele) 61.5% had IUGR <5th percentile and 15.4% had IUGR<10th percentile. The rate of IUGR did not differ significantly between the two groups during pregnancy. Newborns with gastroschisis showed an average weight of 2386 g, and those with omphalocele showed an average weight of 3148 g (P<0.001). Nevertheless, newborns with omphalocele were more frequently eutrophic than those with gastroschisis (88.8% vs. 52.2%, P=0.079). On average, only one surgical intervention was necessary for the definitive repair of the defect (65.5% of the newborns). Children with gastroschisis remained hospitalized nearly twice as long as children with an omphalocele (38 vs. 20 days). IUGR rates during pregnancy did not differ significantly between fetuses with gastroschisis and omphalocele although patients with defects of omphalocele were more frequently eutrophic at birth. Most newborns needed only one operation for definitive surgical treatment. The mean hospitalization time after this intervention was 4 weeks. PMID- 22085154 TI - Risk factors for preterm delivery with placenta previa. AB - AIMS: To identify factors associated with preterm delivery in cases of sonographically identified placenta previa. METHODS: Pregnancies with sonographic evidence of placenta previa at >= 28 weeks were identified. Demographic information, antepartum course, and delivery information were extracted from electronic medical records. Statistical analysis was performed with Fisher's exact test, Mann-Whitney U, Spearman's rho (correlation), and logistic regression. Continuous data are presented as median (interquartile range). RESULTS: Of 113 singleton pregnancies with placenta previa, 54 (48%) delivered at term and 59 (52%) delivered preterm. Fifty-one (45%) experienced antepartum bleeding at a median gestational age of 31 weeks (29-33 weeks) with a median interval of 20 days (11-33 days) between first bleeding episode and delivery. Women with antepartum bleeding were more likely to be delivered for hemorrhage (36 of 51 vs. 8 of 62, P<0.001) and delivered emergently (40 of 51 vs. 14 of 62, P<0.001). Antepartum bleeding before 34 weeks had a positive predictive value of 88% for preterm birth and 83% for emergent delivery. CONCLUSION: In pregnancies with placenta previa, antepartum bleeding is a strong predictor of preterm delivery. PMID- 22085155 TI - Novel dinuclear platinum(II) complexes containing mixed nitrogen-sulfur donor ligands. AB - A series of novel dinuclear platinum(II) complexes were synthesized containing a mixed nitrogen-sulfur donor bidentate chelate system in which the two platinum centers are connected by an aliphatic chain of variable length. The bidentate chelating ligands were selected to stabilize the complex toward decomposition. The pK(a) values and reactivity of the four synthesized complexes, namely, [Pt(2)(S(1),S(4)-bis(2-pyridylmethyl)-1,4-butanedithioether)(OH(2))(4)](4+) (4NSpy), [Pt(2)(S(1),S(6)-bis(2-pyridylmethyl)-1,6 hexanedithioether)(OH(2))(4)](4+) (6NSpy), [Pt(2)(S(1),S(8)-bis(2-pyridylmethyl) 1,8-octanedithioether)(OH(2))(4)](4+) (8NSpy), and [Pt(2)(S(1),S(10)-bis(2 pyridylmethyl)-1,10-decanedithioether)(OH(2))(4)](4+) (10NSpy), were investigated. This system is of special interest because only little is known about the substitution behavior of dinuclear platinum complexes that contain a bidentate chelate that forms part of the aliphatic bridging ligand. Moreover, the ligands as well as the dinuclear complexes were examined in terms of their cytotoxic activity, and the 10NSpy complex was found to be active. Spectrophotometric acid-base titrations were performed to determine the pK(a) values of all the coordinated water molecules. The substitution of coordinated water by thiourea was studied under pseudo-first-order conditions as a function of nucleophile concentration, temperature, and pressure, using stopped-flow techniques and UV-vis spectroscopy. The results for the dinuclear complexes were compared to those for the corresponding mononuclear reference complex [Pt(methylthiomethylpyridine)(OH(2))(2)](2+) (Pt(mtp)), by which the effect of the increasing aliphatic chain length of the bridged complexes could be investigated. The results indicate that there is a clear interaction between the two platinum centers, which becomes weaker as the chain length between the metal centers increases. Furthermore, differences and similarities of the N,S-system were compared to the corresponding dinuclear N,N-system studied previously in our group. In addition, quantum chemical calculations were performed to support the interpretation and discussion of the experimental data. PMID- 22085157 TI - New updated GRAC Fifth Edition with searchable online version Launch of new portal Guide to Pharmacology in association with NC-IUPHAR Transporter-Themed Issue. PMID- 22085158 TI - Transporters are an under-developed therapeutic target. Discuss. PMID- 22085159 TI - Do hairdressers in Denmark have their hand eczema reported as an occupational disease? Results from a register-based questionnaire study. AB - BACKGROUND: Occupational hand eczema is common in hairdressers, owing to wet work and chemicals. OBJECTIVES: To estimate whether hairdressers in Denmark have their hand eczema reported as an occupational disease and to clarify the reasons for not reporting. METHODS: A register-based study was performed, comprising trained hairdressers (n = 7840), using a self-administered postal questionnaire including questions on hand eczema and it being reported as an occupational disease. A response rate of 67.9% (n = 5324) was obtained. RESULTS: Overall, 2186 respondents ever had hand eczema; 71.3% were apprentices at the time of hand eczema onset. The majority (61.9%) had had hand eczema several times and 21.3% (almost) all of the time, but only 20.7% had reported their hand eczema as being occupational to the National Board of Industrial Injuries (Denmark). A positive association between severity of hand eczema and filing a report was found (odds ratio 19.2; 95% confidence interval 8.18-45.06). The main reasons for not reporting were 'I thought it would eventually get better' (40.4%) and 'My doctor didn't tell me it was possible to report it' (26.6%). CONCLUSIONS: Hand eczema is considerably under-reported as an occupational disease; the perception of hand eczema among hairdressers and the lack of reporting from doctors are the main reasons for this. PMID- 22085161 TI - Gender-specific clinicopathological features and survival in patients with renal cell carcinoma (RCC). AB - There has been some controversy about the gender differences in survival in patients with RCC. Korean women with RCC had a lower proportion of clear cell histology and a higher proportion of chromophobe histology. This histological difference might have driven the better survival rates in Korean women. OBJECTIVE: To assess whether there are gender-specific differences in the clinicopathological features and prognosis in a large cohort of Korean patients with renal cell carcinoma (RCC) compared with Western patients. PATIENTS AND METHODS: Medical records of 1616 patients clinically diagnosed with RCC who underwent partial or radical nephrectomy were analysed between January 1988 and July 2009. In all, 1508 patients diagnosed with RCC based on pathology reports were included for evaluation. The mean follow-up period was 73.1 months. The gender-specific differences in the clinicopathological features and survival rates were evaluated using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: Of the 1508 patients, 439 (29.1%) were women. Korean men had a higher proportion of clear cell histology (84.3% vs 72.0%, P < 0.001) and a lower percentage of chromophobe histology (5.2% vs 12.5%, P < 0.001) than Korean women. There were no gender-specific differences in pathological T stage, positive lymph nodes or distant metastases, or Fuhrman's nuclear grade (P > 0.05). For both cancer-specific and overall survival, Kaplan-Meier curves showed that women had a better survival rate than men (P = 0.039 and P = 0.015, respectively). CONCLUSIONS: Korean women with RCC had significantly better survival rates than Korean men. Additionally, Korean women with RCC had a lower proportion of clear cell histology and a higher proportion of chromophobe histology. This histological difference might have driven the better survival rates in Korean women. PMID- 22085162 TI - Hypothesis-based weight-of-evidence evaluation of the neurodevelopmental effects of chlorpyrifos. AB - We used a hypothesis-based weight-of-evidence (HBWoE) approach to analyze the evidence regarding the hypothesis that chlorpyrifos can cause neurodevelopmental effects below the threshold for inhibition of acetylcholinesterase activity in the nervous system, which is an established mode of action for chlorpyrifos neurotoxicity. The epidemiology data do not consistently demonstrate associations between chlorpyrifos exposure and neurodevelopmental toxicity, and the animal toxicity data do not provide clear evidence that neurodevelopmental effects occur at doses below the threshold for acetylcholinesterase inhibition. The alternative mechanisms proposed to underlie potential neurodevelopmental effects in humans have been observed in the absence of acetylcholinesterase inhibition in a few in vitro studies but not in the developing brain in vivo. We provide perspective on the HBWoE approach compared with frameworks developed by the United States Environmental Protection Agency and the European Center for Ecotoxicology and Toxicology of Chemicals. We suggest that our HBWoE approach offers advantages over these frameworks in providing a better perspective on how to integrate all of the relevant data and how to use each line of evidence to inform the integration of other kinds of data or compare alternative hypotheses. Based on an HBWoE analysis, we conclude that a causal association between chlorpyrifos exposure and neurodevelopmental effects in the absence of acetylcholinesterase inhibition in the brain is not plausible in humans, and the few positive associations observed in epidemiology studies are most likely attributable to alternative explanations. PMID- 22085160 TI - Acute varicella zoster encephalitis without evidence of primary vasculopathy in a case-series of 20 patients. AB - Varicella zoster virus (VZV) is a leading cause of acute viral encephalitis but little is known about its clinical, biological and imaging features. Furthermore, the most favourable treatment regimen has not been determined. We studied a prospective cohort of 20 HIV-negative patients presenting with acute VZV encephalitis caused by primary infection or reactivation. VZV was identified in 16 of 20 cases by PCR detection of the DNA in the cerebrospinal fluid. The four remaining cases occurred during or soon after a VZV rash. The median age of the 17 adults was 76 (19-86) years; the three other patients were children (0.5-5 years). Three patients were immunocompromised. Nine adult patients presented with a rash. Eighteen patients presented with fever and an acute encephalitic syndrome: diffuse brain dysfunction, focal neurological signs, seizures and cranial nerve palsies. Three patients presented with either ventricular or subdural haemorrhage, one with myelitis, and one with asymptomatic stenosis of the middle cerebral artery. The imaging was either normal or revealed non specific abnormalities such as cortical atrophy but no evidence of stroke. All patients were given acyclovir at various dosages and durations but the case fatality rate remained high (15%) and sequelae were frequently observed either at discharge or at follow-up 3 years later. PMID- 22085164 TI - Eradicating polio: persisting challenges beyond endemic countries. PMID- 22085165 TI - Current challenges for the creation of effective vaccines against drugs of abuse. PMID- 22085167 TI - Rotarix(r): vaccine performance 6 years postlicensure. AB - Rotarix((r)) was first licensed in 2004 and rapidly introduced into private and public markets worldwide. In a previous 2009 article, we reviewed the impact of rotavirus-associated disease, the rationale for different vaccines, prelicensure efficacy studies and cost-effectiveness studies for Rotarix. As of September 2011, Rotarix had been licensed in 123 countries in the Americas, Europe, Australia, Africa and Asia, of which 27 have incorporated the vaccine into national or regional immunization programs. The current review intends to provide the reader with further insight into this vaccine, focusing mainly on the new information obtained after a 6-year postlicensure period. This review will provide only a brief summary of prelicensure studies extensively discussed in the previous publication and refer, in more depth, to the worldwide experience with the vaccine, vaccine impact, and safety observed in effectiveness and observational studies, including a particular analysis on protection against rotavirus G2P[4]. PMID- 22085168 TI - BiovaxID(r): a customized idiotype vaccine for the treatment of B-cell lymphoma. AB - Most patients with B-cell lymphoma face an often incurable disease, particularly those diagnosed with an indolent subtype. The addition of passive immunotherapy to old and new chemotherapy regimens has improved both response rates and disease free survival, leading in many cases to an extended overall survival. However, a cure remains elusive in most cases. For this reason, the patient- and tumor specific idiotype, that is the collection of epitopes exclusively presented by the tumor clone's surface immunoglobulin, has been extensively studied as a privileged target for vaccine therapy, aiming at preventing disease re-occurrence after standard treatment. BiovaxID((r)) (Biovest International, FL, USA), the most clinically advanced among such therapeutic vaccines, finds itself at a crucial turning point when it comes to further development. Both clinical trials in which it has been formally employed have shown intriguing results. Independent studies using slightly different versions of a conceptually identical vaccine provided all proofs of principle required to ascertain the vaccine's value - biological and clinical efficacy as well as clinical benefit. However, all these data have failed to bring an idiotype vaccine to the market owing to reasons that often have very little to do with the product itself. In fact, some successful studies were not conceived with this goal in mind, while others simply did not enroll enough patients to convincingly make their case for regulatory approval. It is likely that one or more new clinical trials will have to be successfully completed to reach the ultimate goal - that is, to make BiovaxID available to most patients and to adequately position it in the very crowded therapeutic algorithm of B-cell lymphoma. PMID- 22085169 TI - Vaccine-preventable diseases and their impact on Latin American children. AB - A joint meeting of the Latin American Society of Pediatric Infectious Diseases, the Dominican Society of Pediatrics and the Dominican Society of Vaccinology was held in the Dominican Republic. This report highlights the most relevant issues that were presented and discussed about vaccine-preventable diseases, their epidemiology and impact in Latin American children, the need to move forward and expand national immunization programs and the economical and political obstacles to introduce 'new' vaccines. These include those against Streptococcus pneumoniae, rotavirus, hepatitis A, varicella, Neisseria meningitidis, Bordetella pertussis, influenza and human papillomavirus, among others. PMID- 22085170 TI - Do new TB vaccines have a place in the Expanded Program on Immunization? AB - Several new TB vaccines are currently undergoing clinical trials. Among the most promising is a vaccine based upon the modified vaccinia virus Ankara-expressing mycobacterial antigen 85A (MVA85A). Given the widespread use of the current TB vaccine, BCG, many of the new TB vaccines are being tested for their ability to boost BCG-induced immunity. The introduction of a new TB vaccine into routine use would be facilitated by its coadministration with other vaccines as a part of the WHO's Expanded Program on Immunization (EPI). In the article under review the authors tested the immunogenicity of MVA85A given alone or in combination with EPI vaccines to infants in The Gambia. Antigen 85A-specific production of IFN gamma by peripheral blood cells was reduced significantly in infants coimmunized with EPI vaccines compared with infants who received the MVA85A vaccine alone. This study highlights a potentially important issue, which should be addressed prior to the introduction of new TB vaccines and, perhaps, other vaccines that require the induction of a so-called Type 1 T-cell-mediated immune response. PMID- 22085171 TI - Salmonella expressing detoxified lipopolysaccharide is immunogenic and protective both as an attenuated vaccine and for delivery of foreign antigens. AB - The construction of safe and protective vaccines, derived from human pathogens that have been genetically modified to remove pathogenicity, is often easier to accomplish on paper than it is in the laboratory. Kong and colleagues have pursued a clever strategy to reduce the reactogenicity of attenuated Salmonella oral vaccines by genetically modifying the surface lipopolysaccharide to lower endotoxic activity. The resulting candidate vaccine strains were highly reduced in virulence yet were able to confer protection in a mouse model against challenge with virulent Salmonella. Remarkably, these strains could also be further modified to present foreign antigens from unrelated human pathogens and again confer protection against heterologous challenge. This work brings important new tools to bear on solving the problem of creating efficacious attenuated bacterial vaccines that maximize both safety and immunogenicity in clinical trials. PMID- 22085172 TI - Influenza viral neuraminidase: the forgotten antigen. AB - Influenza is the most common cause of vaccine-preventable morbidity and mortality despite the availability of the conventional trivalent inactivated vaccine and the live-attenuated influenza vaccine. These vaccines induce an immunity dominated by the response to hemagglutinin (HA) and are most effective when there is sufficient antigenic relatedness between the vaccine strain and the HA of the circulating wild-type virus. Vaccine strategies against influenza may benefit from inclusion of other viral antigens in addition to HA. Epidemiologic evidence and studies in animals and humans indicate that anti-neuraminidase (NA) immunity will provide protection against severe illness or death in the event of a significant antigenic change in the HA component of the vaccine. However, there is little NA immunity induced by trivalent inactivated vaccine and live attenuated influenza vaccine. The quantity of NA in influenza vaccines is not standardized and varies significantly among manufacturers, production lots and tested strains. The activity and stability of the NA enzyme is influenced by concentration of divalent cations. If immunity against NA is desirable, a better understanding of how the enzymatic properties affect the immunogenicity is needed. PMID- 22085173 TI - European Vaccine Initiative: lessons from developing malaria vaccines. AB - For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation. PMID- 22085174 TI - Hepatitis B vaccine effectiveness in the face of global HBV genotype diversity. AB - Recombinant hepatitis B vaccines are of the A2 genotype; one of ten known genotypes whose distribution varies globally. Reports of rare HBV infections in blood donors with an imbalance of non-A2 genotype HBV in vaccinated subjects have raised questions about the cross-protection afforded by HBV-A2 vaccines. Infections in HBV vaccinees were asymptomatic and transient, indicating that vaccination prevented clinical disease. Preclinical data demonstrate cross reactivity and cross-protection by A2 vaccines against non-A2 HBV genotypes. Substantial improvements in HBV control have been demonstrated in countries with diverse genotype distribution that have introduced universal childhood HBV vaccination programs. Available data show that current HBV-A2 vaccines are highly effective in preventing infections and clinical disease caused by all known HBV genotypes. PMID- 22085175 TI - Epidemiology and prevention of meningococcal disease: a critical appraisal of vaccine policies. AB - Meningococcal disease is characterized by a marked variation in incidence and serogroup distribution by region and over time. In several European countries, Canada and Australia, immunization programs, including universal vaccination of infants or toddlers with catch-up campaigns in children and adolescents, aimed at controlling disease caused by meningococcal serogroup C have been successful in reducing disease incidence through direct and indirect protection. More recently, meningococcal conjugate vaccines targeting disease caused by serogroups A, C, W 135 and Y have been licensed and are being used in adolescent programs in the USA and Canada while a mass immunization campaign against serogroup A disease has been implemented in Africa. Positive results from clinical trials using vaccines against serogroup B disease in various age groups suggest the possibility of providing broader protection against serogroup B disease than is provided by the currently used outer membrane vesicle vaccines. The purpose of our review of meningococcal epidemiology and assessment of existing policies is to set the stage for future policy decisions. Vaccination policies to prevent meningococcal disease in different regions of the world should be based on quality information from enhanced surveillance systems. PMID- 22085178 TI - Regiospecific synthesis of 1,2-disubstituted (hetero)aryl fused imidazoles with tunable fluorescent emission. AB - A palladium-catalyzed two or fourfold amination was established that allows regiospecific synthesis of a diversity-oriented library of 1,2-disubstituted (hetero)aryl fused imidazoles, and provides an exceptional tool for the discovery of fluorescent scaffolds with tunable fluorescence emission. These fluorophores have been applied as fluorescent probes for live cell imaging. PMID- 22085176 TI - The long-term potential of biodegradable poly(lactide-co-glycolide) microparticles as the next-generation vaccine adjuvant. AB - Biodegradable polymeric microparticles of poly(lactide-co-glycolide) (PLG) have been extensively evaluated for drug delivery and vaccine applications over the last three decades. Despite a wealth of studies on the use of PLG microparticles in vaccines through controlled release of antigens, there is no commercial PLG based vaccine as yet. The key challenge that prevented the development of PLG microparticles as commercial vaccines was the instability of encapsulated antigen. Over the years, advancements were made towards maintaining antigen integrity during PLG microparticle preparation and sterilization. In parallel and independently, development of PLG microparticles as therapeutic commercial products established PLG with an excellent safety record in humans, and as a suitable candidate for next-generation vaccines. Through the combination of Toll like receptor agonist encapsulation and surface adsorption of antigen, PLG microparticles can be used as a vaccine adjuvant to address unmet medical needs, such as vaccines against HIV, malaria and TB. With strategic development of PLG based vaccines, PLG microparticles can offer advantages over the conventional vaccine adjuvants allowing commercial development of this adjuvant. PMID- 22085179 TI - Glycogen storage and degradation during in vitro growth and differentiation of Giardia intestinalis. AB - Giardia intestinalis is the causative agent of human giardiasis, a common diarrheal illness worldwide. Despite its global distribution and prevalence, many questions regarding its basic biology and metabolism remain unanswered. In this study, we examine the accumulation and degradation of glycogen, an important source of stored carbon and energy, during the in vitro growth and differentiation of G. intestinalis . We report that, as G. intestinalis progresses through its growth cycle, cultures of trophozoites accumulate glycogen during the lag and early logarithmic phases of growth and then utilize this compound during their remaining logarithmic growth. As cultures enter the stationary phase of growth, they re-accumulate glycogen stores. The activity of glycogen phosphorylase, an enzyme involved in glycogen metabolism, also varied throughout in vitro trophozoite growth. During the in vitro induction of trophozoite differentiation into water-resistant cyst forms, the cultures initially accumulated stores of glycogen which diminished throughout transition to the cyst form. This observation is suggestive of a role for glycogen in the differentiation process. These studies represent the first thorough analysis of changes in glycogen content and glycogen phosphorylase activity during G. intestinalis growth and differentiation. PMID- 22085180 TI - Exenatide BID Observational Study (ExOS): results for primary and secondary endpoints of a prospective research study to evaluate the clinical effectiveness of exenatide BID use in patients with type 2 diabetes in a real-world setting. AB - OBJECTIVE: The Exenatide BID Observational Study (ExOS) was designed to evaluate the clinical effectiveness of exenatide BID use in patients with type 2 diabetes (T2D) in a real-world clinical practice setting in the United States. METHODS: Patients were enrolled from 74 practice sites from 9/2007 through 1/2009 and followed for 12 months. The primary effectiveness endpoint was achieving or maintaining hemoglobin A1C of <=7.0%, or an absolute drop of 0.5% from baseline. Secondary measures included absolute and percentage change from baseline for a variety of clinical measures (lipid markers, weight, BMI, etc.), and quality of life (QOL) was assessed using the Impact of Weight on Quality of Life (IWQOL) Lite. RESULTS: A total of 452 patients were included in the primary study population. At baseline, patients (60% female) had mean (SD) age of 55 (11), T2D duration of 9 (8) years, HbA1c of 8.0 (1.7) %, and body mass index (BMI) of 38.2 (7.4) kg/m(2). Family history of T2D was reported in 73.9% of patients. Hypertension was reported in 61.5% of patients, and 47.1% had hyperlipidemia. The HbA1c goal was achieved in 76.3% of the 118 patients with A1C measurements available at 12 months (P < 0.0001). Patients with available clinical measurements achieved significant improvements in HbA1c, weight, BMI, and QOL measurements at 12 months. A mean improvement of 4.56 was seen in the total IWQOL Lite score at 12 months (P = 0.001). The single-arm design of this study is a limitation; however, the overall objective of the study was to observe patients on exenatide BID therapy over time, comparing their status at endpoint to baseline, rather than to make comparisons among different drug therapies. CONCLUSIONS: The Exenatide BID Observational Study supports the clinical effectiveness of exenatide BID observed in previous clinical trials and retrospective database studies. PMID- 22085181 TI - Crystal structure of the zinc-dependent MarR family transcriptional regulator AdcR in the Zn(II)-bound state. AB - Streptococcus pneumoniae adhesin competence regulator (AdcR), the first metal dependent member of the multiple antibiotic resistance regulator (MarR) family of proteins, represses the transcription of a high-affinity zinc-specific uptake transporter, a group of surface antigen zinc-binding pneumococcal histidine triad proteins (PhtA, PhtB, PhtD, and PhtE), and an AdcA homologue (AdcAII). The 2.0 A resolution structure of Zn(II)-bound AdcR reveals a highly helical two-fold symmetric dimer with two distinct metal-binding sites per protomer. Zn(II) is tetrahedrally coordinated by E24, H42, H108, and H112 in what defines the primary sensing site in AdcR. Site 2 is a tetracoordinate site whose function is currently unknown. NMR methyl group perturbation experiments reveal that Zn(II) drives a global change in the structure of apo-AdcR that stabilizes a conformation that is compatible with DNA binding. This co-repression mechanism is unprecedented in MarR transcriptional regulators. PMID- 22085182 TI - The power of play. PMID- 22085183 TI - Drawing attention to difference: dilemmas in discussing dysmorphism with parents. AB - Dysmorphism is a sensitive topic to discuss with parents. Discussing dysmorphism requires careful thought, awareness of parent reactions, practice and reflection. Clinical practice suggests that barriers exist for both parents and health professionals, which make these discussions challenging. Here, we explored the challenges inherent in dialogue about dysmorphism and offer suggestions for communication strategies that are grounded in both theory and practice. PMID- 22085184 TI - Blisters on the scrotum of an infant. PMID- 22085187 TI - An unusual complication of endoscopic intestinal biopsy. PMID- 22085188 TI - An unusual cause of early respiratory distress in a neonate: infective endocarditis. PMID- 22085189 TI - Complete heart block complicating Acute Rheumatic Fever. PMID- 22085190 TI - Child survival and child development in developing countries. PMID- 22085191 TI - Reperfusion syndrome after an endovascular procedure in low birth weight newborn. PMID- 22085192 TI - Cannabinoid receptor 1 gene is associated with alcohol dependence. AB - BACKGROUND: Alcohol dependence (AD) vulnerability is determined by a complex array of genetic factors. Given the potential role of endocannabinoid system in AD, polymorphisms within cannabinoid receptor 1 gene (CNR1) have been potentially associated with susceptibility to this disease. We thus aimed to examine the relationship between 3 allelic variants of CNR1 (rs6454674, rs1049353, and rs806368) and AD. METHODS: Genotyping of the aforementioned polymorphisms was carried out by PCR in 298 male alcoholics (187 of them with AD) and 155 healthy controls. Single-marker, haplotype, and interaction analysis were performed to analyze the influence of CNR1 gene on AD susceptibility. RESULTS: We found an association between CNR1 gene and AD after haplotype analysis. Alcoholic patients with TGT haplotype (corresponding to rs6454674-rs1049353-rs806368 polymorphisms in this order) were less prone to have AD (p = 0.017). Besides, alcoholics with a G/T substitution of the first marker (GGT haplotype) or a C/T substitution of the third marker (TGC haplotype) were more likely to develop AD (p = 0.006 and 0.004, respectively) and an interaction was found between the G allele of rs6454674 single nucleotide polymorphism (SNP) and the C allele of rs806368 SNP (p = 0.009). CONCLUSIONS: Our findings support previously reported associations of CNR1 with dependence to alcohol and other substances and emphasizes the relevance of endocannabinoid system in AD. PMID- 22085193 TI - Single nucleotide polymorphisms of toll-like receptor-4 protect against acne conglobata. AB - BACKGROUND: Former studies have shown that Propionibacterium acnes may stimulate expression of toll-like receptor 4 (TLR4) in keratinocytes of patients with acne vulgaris. OBJECTIVE: To investigate the impact of single nucleotide polumorphisms (SNPs) of the TLR4 gene in acne vulgaris. METHODS: Genomic DNA was isolated from 191 patients with acne vulgaris and 75 healthy controls. Asp299Gly and Thr399Ile SNPs were defined after cutting of the PCR products by restriction enzymes. Sebum of lesions was cultured for P. acnes. RESULTS: No differences in SNP allele frequencies were found between patients and healthy controls. 46.5% of carriers of wild-type alleles were suffering from acne conglobata compared with 28.6% of carriers of SNP alleles (P=0.040). After adjusting for gender, family history of acnes, intake of any therapy and skin isolation of P. acnes, carriage of TLR4 gene SNPs was the only independent variable linked with a protective role against acne conglobata (OR=0.269, P=0.014). No differences were found in the amount of pro-inflammatory cytokines released by peripheral blood mononuclear cells isolated from patients with acne conglobata carrying only wild-type alleles and SNP alleles. CONCLUSIONS: Carriage of gene SNPs is protective against the development of acne conglobata even in the presence of P. acnes. PMID- 22085194 TI - Neurons from senescence-accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol. AB - The senescence-accelerated prone 8 (SAMP8) mouse strain shows early cognitive loss that mimics the deterioration of learning and memory in the elderly and is widely used as an animal model of aging. SAMP8 mouse brain suffers oxidative stress, as well as tau- and amyloid-related pathology. Mitochondrial dysfunction and the subsequent increase in cellular oxidative stress are central to the aging processes of the organism. Here, we examined the mitochondrial status of neocortical neurons cultured from SAMP8 and senescence-accelerated-resistant (SAMR1) mice. SAMP8 mouse mitochondria showed a reduced membrane potential and higher vulnerability to inhibitors and uncouplers than SAMR1 mitochondria. DL buthionine-[S,R]-sulfoximine (BSO) caused greater oxidative damage in neurons from SAMP8 mice than in those from SAMR1 mice. This increased vulnerability, indicative of frailty-associated senescence, was protected by the anti-aging agents melatonin and resveratrol. The sirtuin 1 inhibitor, sirtinol, demonstrated that the neuroprotection against BSO was partially mediated by increased sirtuin 1 expression. Melatonin, like resveratrol, enhanced sirtuin 1 expression in neuron cultures of SAMR1 and SAMP8 mice. Therefore, a deficiency in the neuroprotection and longevity of the sirtuin 1 pathway in SAMP8 neurons may contribute to the early age-related brain damage in these mice. This supports the therapeutic use of sirtuin 1-enhancing agents against age-related nerve cell dysfunction and brain frailty. PMID- 22085199 TI - Michael addition reactions for the modification of gold nanoparticles facilitated by hyperbaric conditions. AB - The chemical interfacial modification of organic solvent soluble 2.4 +/- 0.5 nm maleimide-modified monolayer protected gold nanoparticles (2-C(12)AuNPs) with primary or secondary amines via Michael addition reactions is demonstrated. Michael addition reactions between 2-C(12)AuNPs and primary or secondary amines at ambient temperature and pressure and under the conditions where the AuNP is soluble and stable are possible albeit sluggish, often taking days to weeks to go to completion. The rates and efficacies of the these same reactions are drastically increased at hyperbaric pressure conditions (11 000 atm) with no observed adverse effect to the gold nanoparticle stability. The resulting Michael addition adducts (3-C(12)AuNPs) formed from 2-C(12)AuNPs and the corresponding amines were characterized by TEM and by comparison of the (1)H NMR spectra of the 3-C(12)AuNPs with those of model reactions of the same amines with N dodecylmaleimide, 2. The Michael addition reactions occur more readily with 2 rather than 2-C(12)AuNPs, consistent with the local environment of the latter imposing additional steric or other barriers to the reaction. The use of hyperbaric conditions makes the reaction of the organic solvent soluble 2 C(12)AuNP via Michael addition a viable interfacial modification process that is otherwise impractical. The results also suggest that it is a useful protocol for facilitating Michael addition reactions generally in solution at low temperatures. PMID- 22085200 TI - Electronic and molecular structures of the members of the electron transfer series [Cr(tbpy)3]n (n = 3+, 2+, 1+, 0): an X-ray absorption spectroscopic and density functional theoretical study. AB - The electron transfer series of complexes [Cr((t)bpy)(3)](n)(PF(6))(n) (n = 3+, 2+, 1+, 0 (1-4)) has been synthesized and the molecular structures of 1, 2, and 3 have been determined by single-crystal X-ray crystallography; the structure of 4 has been investigated using extended X-ray absorption fine structure (EXAFS) analysis. Magnetic susceptibility measurements (4-300 K) established an S = 3/2 ground state for 1, an S = 1 ground state for 2, an S = 1/2 ground state for 3, and an S = 0 ground state for 4. The electrochemistry of this series in CH(3)CN solution exhibits three reversible one-electron transfer waves. UV-vis/NIR spectra and Cr K-edge X-ray absorption spectra (XAS) are reported. The same experimental techniques have been applied for [Cr(III)(tacn)(2)]Br(3).5H(2)O (5) and [Cr(II)(tacn)(2)]Cl(2) (6), which possess an S = 3/2 and an S = 2 ground state, respectively (tacn = 1,4,7-triazacyclononane, a tridentate, pure sigma donor ligand). The Cr K-edge XAS spectra of the corresponding complexes K(4)[Cr(II)(CN)(6)].10H(2)O (S = 1) (7) and K(3)[Cr(III)(CN)(6)] (S = 3/2) (8) have also been recorded. All complexes have been studied computationally with density functional theory (DFT) using the B3LYP functional. The molecular and electronic structures of the anionic members of the series [Cr(bpy)(3)](1-,2-,3-) have also been calculated. It is unequivocally shown that all members of the electron transfer series 1-4 and [Cr(bpy)(3)](n) (n = 3+, 2+, 1+, 0, 1-, 2, 3-) possess a central Cr(III) ion ((t(2g))(3), S = 3/2). The three N,N'-coordinated neutral (bpy(0)) ligands in the trication 1 and [Cr(III)(bpy)(3)](3+) are one electron reduced in a stepwise fashion to localized one, two, and three pi radical anions (bpy(*))(1-) in the dicationic, monocationic, and neutral species, respectively. Complexes 2 and [Cr(bpy)(3)](2+) cannot be described as low-spin Cr(II) species; they are in fact best described as [Cr(III)((t)bpy(*))((t)bpy(0))(2)](2+) and [Cr(III)(bpy(*))(bpy(0))(2)](2+) species. Further one-electron reductions yield one, two, and three diamagnetic (bpy(2-))(2-) dianions in the mono-, di-, and trianion. Thus, [Cr(III)(bpy(2 ))(3)](3-) is a normal Werner-type Cr(III) (!) species. In all complexes containing (bpy(*))(1-) ligands, the ligand spins are strongly antiferromagnetically coupled to the spins of the central Cr(III) ion (d(3), S(Cr) = 3/2) affording the observed ground states given above. Thus, all redox chemistry of [Cr(bpy)(3)](n) complexes is ligand-based and documents that the ligand 2,2'-bipyridine is a redox noninnocent ligand; it exists in three oxidation levels in these complexes: as N,N'-coordinated neutral (bpy(0)), monoanionic pi-radical (bpy(*))(1-), and diamagnetic dianionic (bpy(2-))(2-). PMID- 22085201 TI - A systematic review of early postpartum medroxyprogesterone receipt and early breastfeeding cessation: evaluating the methodological rigor of the evidence. AB - BACKGROUND: Breastfeeding has numerous maternal and infant benefits. Progesterone contraception after birth is frequently recommended, but because a decrease in progesterone is required to initiate lactation, early postpartum progesterone contraception use could inhibit lactation. The purpose of this article is to critically evaluate the scientific basis for conflicting clinical recommendations related to postpartum medroxyprogesterone use among breastfeeding women. METHODS: Relevant peer-reviewed literature was identified through a comprehensive search of PubMed through December 2010. The search was restricted to clinical trials, randomized clinical trials, or comparative studies written in English and conducted among humans. The studies included in this review addressed the effect of medroxyprogesterone administration at <6 weeks postpartum on breastfeeding exclusivity and/or duration and measured breastfeeding outcomes at >= 6 weeks postpartum. RESULTS: Of the 20 articles identified, only three studies satisfied the inclusion criteria. However, all three studies were of low-quality methodological rigor, and none accounted for potential confounders. CONCLUSION: Current evidence is methodologically weak and provides an inadequate basis for inference about a possible causal relationship between early postpartum medroxyprogesterone use and poor breastfeeding outcomes. However, given the presence of a strong biological model describing the potential deleterious effect of postpartum medroxyprogesterone use on lactation, further research that improves on current literature is warranted. Meanwhile, we recommend that potential breastfeeding risks associated with early (<6 weeks) postpartum medroxyprogesterone use be disclosed to allow for a fully informed consent and decision-making process. PMID- 22085203 TI - The ability of prostate-specific antigen (PSA) density to predict an upgrade in Gleason score between initial prostate biopsy and prostatectomy diminishes with increasing tumour grade due to reduced PSA secretion per unit tumour volume. AB - Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Due to sampling error, the Gleason score of clinically localized prostate cancer is frequently underestimated at the time of initial biopsy. Given that this may lead to inappropriate surveillance of patients with high-risk disease, there is considerable interest in identifying predictors of significant undergrading. Recently PSAD has been proposed to be an accurate predictor of subsequent upgrading in patients diagnosed with Gleason 6 disease on biopsy. We examined the predictive characteristics of PSAD in patients with low- and intermediate-risk disease on biopsy subsequently treated with radical prostatectomy. We found that although PSAD was a significant predictor of upgrade of biopsy Gleason 6 and 3 + 4 = 7 tumours, it failed to predict upgrading in patients with Gleason 7 tumours taken as a whole. When we explored reasons for this discrepancy, we found that the amount of PSA produced per unit tumour volume decreased with increasing Gleason score, thereby diminishing the predictive value of PSAD. OBJECTIVES: To analyse the performance of PSA density (PSAD) as a predictor of Gleason score upgrade in a large cohort stratified by Gleason score. We and others have shown that an upgrade in Gleason score between initial prostate biopsy and final radical prostatectomy (RP) pathology is a significant risk factor for recurrence after local therapy. PATIENTS AND METHODS: Patients undergoing RP with matching biopsy information were identified from two prospective databases. Patients were analysed according to the concordance between biopsy and final pathology Gleason score in three paired groups: 6/>6, 3 + 4/>3 + 4, 7/>7. Receiver-operating characteristic (ROC) curves were generated stratified by Gleason score, and the area under the curve (AUC) calculated. Logistic regression models were fitted to identify significant predictors of tumour upgrade. RESULTS: From 1516 patients, 435 (29%) had an upgrade in Gleason score. ROC analysis showed a decline in AUC with increasing biopsy Gleason score, from 0.64 for biopsy Gleason score 6, to 0.57 for Gleason score 7. In logistic regression models containing pretreatment variables, e.g. clinical stage and number of positive cores, for Gleason score 6 and 3 + 4, PSAD was the strongest predictor of subsequent tumour upgrade (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.18-1.83, P= 0.001 and OR 1.37, 95% CI 1.14-1.67, P= 0.002, respectively). Surprisingly, in tumours upgraded from Gleason score 7 to >7, PSAD was not predictive even on univariable analysis, whereas clinical stage and number of positive cores were significant independent predictors. To explore the relationship between serum PSA and Gleason score, tumour volume was calculated in 669 patients. There was a strong association between Gleason score and tumour volume, with the median volume of Gleason score 7 and Gleason score >7 tumours being approximately twice and four-times that of Gleason score 6 tumours, respectively (P < 0.001). In contrast, the median serum PSA level per millilitre tumour volume decreased significantly with increasing grade, from 5.4 ng/mL for Gleason score 6 to 2.1 ng/mL for >7 (P < 0.001). CONCLUSIONS: There is a strong correlation between Gleason score and tumour volume in well/intermediate differentiated tumours, and as they produce relatively high amounts of PSA per unit volume of cancer, high PSAD is the strongest single predictor of tumour undergrading. However, as higher grade tumours produce less PSA per unit volume, PSAD loses its predictive ability, and other clinical markers of tumour volume such as palpable disease and numbers of positive cores become more predictive. PMID- 22085202 TI - The role of autophagy in unilateral ureteral obstruction rat model. AB - AIM: Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death or proliferation. Unilateral ureteral obstruction (UUO) is a model of progressive renal fibrosis in the obstructed kidney. And UUO is followed by compensatory cellular proliferation in the contralateral kidney. We investigate the role of autophagy in the obstructed kidney and contralateral kidney after UUO. METHODS: To obtain the evidence and the patterns of autophagy during UUO, the rats were sacrificed 3, 7 and 14 days after UUO. To examine the efficacy of the autophagy inhibitors, 3-methyladenine (3-MA), the rats were treated daily with intraperitoneal injection of 3-MA (30 mg/kg per day) for 7 days. RESULTS: After UUO, autophagy was induced in the obstructed kidney in a time-dependent manner. Inhibition of autophagy by 3-MA enhanced tubular cell apoptosis and tubulointerstitial fibrosis in the obstructed kidney after UUO. In the contralateral kidney, autophagy was also induced and prolonged during UUO. Inhibition of autophagy by 3-MA increased the protein expression of proliferating cell nuclear antigen significantly in the contralateral kidney after UUO. The Akt-mammalian target of rapamycin (mTOR) signalling pathway was involved in the induction of autophagy after UUO in both kidneys. CONCLUSION: Our present results support that autophagy induced by UUO has a renoprotective role in the obstructed kidney and regulatory role of compensatory cellular proliferation in the contralateral kidney through Akt-mTOR signalling pathway. PMID- 22085204 TI - Differentiation of induced pluripotent stem cells into dental mesenchymal cells. AB - Similar to embryonic stem cells, induced pluripotent stem (iPS) cells can differentiate into various cell types upon appropriate induction, and thus, may be valuable cell sources for regenerative medicine. However, iPS cells have not been reported to differentiate into odontogenic cells for tooth regeneration. Here we demonstrated that neural crest-like cells (NCLC) derived from mouse iPS cells have the potential to differentiate into odontogenic mesenchymal cells. We developed an efficient culture protocol to induce the differentiation of mouse iPS cells into NCLC. We confirmed that the cells exhibited neural crest (NC) cell markers as evidenced by immunocytochemistry, flow cytometry, and real-time reverse transcription-polymerase chain reaction. Further, in recombination cultures of NCLC and mouse dental epithelium, NCLC exhibited a gene expression pattern involving dental mesenchymal cells. Some NCLC also expressed dentin sialoprotein. Conditioned medium of mouse dental epithelium cultures further enhanced the differentiation of NCLC into odontoblasts. These results suggest that iPS cells are useful cell sources for tooth regeneration and tooth development studies. PMID- 22085206 TI - Enhancing nursing knowledge using high-fidelity simulation. AB - The use of high-fidelity simulation as an accepted substitute for traditional clinical learning experiences in nursing education has gained acceptance over the past decade, as evidenced by the California Board of Registered Nursing now allowing up to 25% of student clinical learning to occur in simulation laboratories. However, little research evidence has documented the efficacy of these simulated learning experiences, particularly on objective outcomes such as examination performance. Therefore, this study examined the effects of high fidelity simulation participation on knowledge acquisition in 104 undergraduate nursing students. Students who participated in high-fidelity simulation scenarios scored significantly higher on examinations than students who did not. These findings provide beginning evidence that high-fidelity simulation can be an effective substitute for traditional clinical experience. More importantly, the findings may help boards of nursing more effectively regulate the use of high fidelity simulation in the future. PMID- 22085207 TI - Effects of communication training on real practice performance: a role-play module versus a standardized patient module. AB - This study investigated the effectiveness of modules involving standardized patients and role-plays on training communication skills. The first module involved standardized patients and an Objective Structured Clinical Examination (OSCE); the second module consisted of peer role-plays and a written examination. A randomized posttest-only control group design with first-year nursing students was used. The intervention group received one-to-one communication training with direct oral feedback from the standardized patient. The control group had training with peer role-playing and mutual feedback. The posttest involved students' rating their self-efficacy, and real patients and clinical supervisors evaluated their communication skills. No significant differences were found between self-efficacy and patient ratings. However, the clinical supervisors rated the intervention group's communication skills to be significantly (p < 0.0001) superior. Assessments by clinical supervisors indicate that communication training modules including standardized patients and an OSCE are superior to communication training modules with peer role-playing. PMID- 22085208 TI - The critical difference assignment: an innovative instructional method. AB - Nurse educators are faced with the challenge of developing and evaluating learning methods that promote knowledge acquisition, problem solving, and the development of clinical judgment to meet today's expectations of new graduates. Clinical judgment is at the heart of decision making and drives nursing action. It encompasses perceptions and intellectual processing of information through mental operations of reasoning, resulting in appropriate actions. An instructional method, entitled the Critical Difference Assignment, aimed at developing clinical judgment has been developed and piloted at a southwestern university. This instructional method requires students in small groups to engage in intellectual processing of case study information using mental operations of reasoning to discriminate between two case studies through a process of comparing and contrasting the data. PMID- 22085209 TI - Developing nontraditional community health placements. AB - Building capacity for student clinical experiences has become a key concern for nurse educators in the 21st century. For community health faculty, traditional placements at public health departments or other health-affiliated organizations often do not provide adequate numbers or types of placement opportunities. Wishing to expand experiences for its undergraduate program, faculty at a midwestern university have developed and nurtured long-standing collaborative relationships with organizations not typically used by schools of nursing. Such partnerships are often called "nontraditional," with the understanding that they are not affiliated with the typical health sector organizations. This article introduces two of these partnerships, describes the process used to establish and maintain them, and identifies the outcomes achieved by students, clients, and organizations. PMID- 22085210 TI - Knowing nursing through inquiry: engaging students in knowledge creation. AB - Two nurse educators share a nursing knowledge course, which was created as a forum for questioning and discovery, thereby revealing a process of knowing nursing through inquiry. The process of inquiry in nursing praxis is emphasized, facilitating students' understanding that they are knowledge-users and creators. With students, we explore the construction of praxis, which includes being/becoming (ontology), knowing (epistemology), and doing (actions with consequences). Nursing knowledge is understood to arise from philosophy, world views, nursing theories, patterns of knowing, evidence-based research, and standards of practice. Students are encouraged to critically reflect on and use what is congruent with their praxis and to construct new knowledge. Exemplars from nurse educators and students are presented as evidence of our claim for furthering the science of nursing education. PMID- 22085211 TI - A prebaccalaureate PhD option: shaping the future of research-focused doctoral education. AB - The future of PhD education in nursing is at a crossroads. Our current practice of primarily enrolling post-master's students with years of clinical experience is not producing an adequate number of graduates who are able to make significant and sustained contributions to nursing research. Therefore, it is timely to consider educational innovations that encourage a different population of students to consider doctoral research training. A prebaccalaureate or early entry option to the PhD in nursing is a means toward this end. At the University of Wisconsin-Madison, a select group of prenursing students and students beginning the nursing major are offered an early admission to PhD education. A key component of the Early Entry PhD Option is immediate and intensive research training with an established nurse faculty researcher. In this article, the authors describe the curriculum of a prebaccalaureate, research-focused doctoral option and its early results. PMID- 22085212 TI - Insight into potential Cu(II)-binding motifs in the four pseudorepeats of tau protein. AB - Tau protein and Cu(II) are believed to be associated with the pathogenesis of Alzheimer's disease. However, little is known about atomic-level interactions between tau protein and Cu(II). Herein, we suggest, on the basis of electron spin resonance (ESR) data, that the four pseudorepeats of tau protein in the microtubule-binding region play an important role in Cu(II) binding. We use a number of tau protein fragments in order to examine Cu(II)-binding site(s) and binding affinities. Continuous-wave (CW) ESR experiments on the four highly conserved octadecapeptides, each of which is a segment of one of the four pseudorepeats, reveal that the equimolar Cu(II) complexes of the four octadecapeptides are similar to one another in terms of the coordination environment and binding affinity. The spectra obtained with pulsed ESR techniques such as electron spin-echo envelope modulation and hyperfine sublevel correlation provide direct evidence that a histidine residue and a backbone amide group coordinate to Cu(II) in each Cu(II)-octadecapeptide complex. The results of CW and pulsed ESR experiments on some chemically modified peptides indicate that the cysteine residues in the second and third pseudorepeats are unlikely to be involved in Cu(II) binding. On the other hand, similar experiments on tau fragments of the second pseudorepeat with different lengths lead to the conclusion that the affinity for Cu(II) decreases as the octadecapeptide is either truncated or elongated. The high Cu(II)-binding affinity of the octadecapeptide is presumably due to the N-terminal amino group stabilizing the Cu(II)-octadecapeptide complex. Finally, the ESR data for a longer tau fragment that contains two octadecapeptides suggest that the Cu(II) binding site(s) of even longer fragments of tau protein is similar to that of a single octadecapeptide. PMID- 22085213 TI - Structural origin and laser performance of thulium-doped germanate glasses. AB - The structural origin and laser performance of thulium-doped germanate glasses have been studied. The investigation includes two main sections. The first part discusses the Raman spectroscopic and thermal stability of the host glass structure. The low value of the largest phonon energy (850 cm(-1)) reduces the probability of nonradiative relaxation. The large emission cross section of the Tm(3+) : (3)F(4) level (8.69 * 10(-21) cm(2)), the high quantum efficiency of the (3)F(4) level (71%), and the low nonradiative relaxation rate of the (3)F(4) -> (3)H(6) transition (0.09 ms(-1)) illustrate good optical properties of the germanate glass. In the second part, the room-temperature laser action from the thulium-doped germanate glass is demonstrated when pumped by a 790 nm laser diode. The maximum output power of 346 mW and slope efficiency of 25.6% are achieved. PMID- 22085214 TI - Modular synthesis of functionalized bis-bispidine tetraazamacrocycles. AB - An effective synthesis is reported for the construction of highly rigid and preorganized bis-bispidine tetraazamacrocycles bearing either identical or different functionalities. Using essential building blocks derived from N-Boc-N' allylbispidinone, the modular approach facilitates independent incorporation of the functional groups to the macrocyclic framework as well as selective derivatization of one functionality in the presence of another. PMID- 22085216 TI - Silylium-arene adducts: an experimental and theoretical study. AB - The solvent-coordinated [Me(3)Si.arene][B(C(6)F(5))(4)] salts (arene = benzene, toluene, ethylbenzene, n-propylbenzene, isopropylbenzene, o-xylene, m-xylene, p xylene, 1,2,3-trimethylbenzene, 1,2,4-trimethylbenzene, 1,3,5-trimethylbenzene) are prepared and fully characterized. As an interesting decomposition product the formation of bissilylated fluoronium ion [Me(3)Si-F-SiMe(3)](+) was observed and even cocrystallized with [Me(3)Si.arene][B(C(6)F(5))(4)] (arene = benzene and toluene). Investigation of the degradation of [Me(3)Si.arene][B(C(6)F(5))(4)] reveals the formation of fluoronium salt [Me(3)Si-F-SiMe(3)][B(C(6)F(5))(4)], B(C(6)F(5))(3), and a reactive "C(6)F(4)" species which could be trapped with CS(2). Upon addition of CS(2), the formation of a formal S-heterocyclic carbene adduct, C(6)F(4)CS(2)-B(C(6)F(5))(3), was observed. The structure and bonding of substituted [Me(3)Si.arene][B(C(6)F(5))(4)] with arene = R(n)C(6)H(6-n) (R = H, Me, Et, Pr, and Bu; n = 0-6) is discussed on the basis of experimental and theoretical data. X-ray data of [Me(3)Si.arene][B(C(6)F(5))(4)] salts reveal nonplanar arene species with significant cation...anion interactions. As shown by different theoretical approaches (charge transfer, partial charges, trimethylsilyl affinity values) stabilizing inductive effects occur; however, the magnitude of such effects differs depending on the degree of substitution and the substitution pattern. PMID- 22085215 TI - Social and psychological determinants of levels of engagement with an online breast cancer support group: posters, lurkers, and nonusers. AB - Despite the benefits and growing availability of online cancer support groups, many breast cancer patients still do not actively participate in them. To better understand cancer patients' online information- and support-seeking behaviors, this study explores how various social and psychological characteristics predict different levels of engagement with an online breast cancer support group: posters, lurkers, and nonusers. The study sample included 231 recently diagnosed breast cancer patients. Data included baseline survey scores of demographic, disease-related, and psychosocial factors and automatically collected discussion group use data over the 4-month intervention. Patterns of engagement with the cancer support group differed according to the patients' characteristics, suggesting that (a) cancer patients have very different orientations to and engagement with an online support group, and (b) deficits in social and psychological resources may not be barriers to participation in a cancer support group, but rather motivators to interact with other patients. The authors discuss the theoretical and practical implications of their findings. PMID- 22085217 TI - Absolute interdialytic weight gain is more important than percent weight gain for intradialytic hypotension in heavy patients. AB - AIM: Few published reports have mentioned the difference between absolute interdialytic weight gain (IDWG) and IDWG/DW (IDWG%), and subsequent effects on daily dialysis. The aim of present study was to evaluate the difference between absolute IDWG and IDWG% in new haemodialysis patients. METHOD: We retrospectively reviewed the records of 255 patients who recently received conventional haemodialysis for at least 1 year at the same centre from 1997 to 2008. The first 4 weeks after starting haemodialysis was defined as the pre-study period. Data were collected for 5-56 weeks. RESULTS: IDWG% value remained relatively constant in the first year of haemodialysis despite most patients having certain residual renal function. For haemodialysis outcomes, both absolute IDWG and IDWG% were significantly correlated with intradialytic hypotension (IDH) in men and heavy women. After dividing patients into four strata, which according to the gender and the median dry weight, stepwise multivariate linear regression analysis showed that absolute IDWG, rather than IDWG%, was an independent risk factor for IDH in heavy men (Beta = 0.585, P < 0.001) and heavy women (Beta= 0.458, P < 0.001). CONCLUSIONS: Absolute IDWG, rather than IDWG%, is an independent risk factor for IDH in heavy haemodialysis patients. Therefore, higher absolute IDWG needs to be strictly controlled despite the corresponding IDWG% possibly being relatively small in heavy haemodialysis patients. PMID- 22085218 TI - Prevalence of Bacillus cereus and associated risk factors in Chinese-style fried rice available in the city of Colombo, Sri Lanka. AB - The present study aimed to assess the prevalence of Bacillus cereus and its associated risk factors in Chinese-style fried rice available in Colombo city. In 200 samples of fried rice the prevalence of B. cereus was 56%. The prevalence by variety of fried rice was chicken (20.0%), vegetable (18.0%), seafood (10.0%), egg (5.0%), mixed (2.0%), and beef (1.0%). Of analyzed samples, 28 (14%) had colony counts >10(6) colony forming units per gram (cfu/g), the infectious dose for B. cereus food borne outbreaks. Occurrence of >10(6) cfu/g of B. cereus were associated with storage of boiled rice at room temperature (p=0.030), >4 hours of storage at room temperature (p=0.042) and cooking frequency of more than once per dining session (p=0.017). The type of rice and the quantity boiled per day were not independent risk factors for high B. cereus counts. Majority of B. cereus isolates (53.7%) in this study were not typable. The serotypes observed included H15 (14.3%), H19 (14.3%), and H20 (10.7%). These serotypes are known to be associated with both emetic and diarrheal syndromes. All isolates were sensitive to ciprofloxacin (100%), erythromycin (100%), gentamicin (100%), chloramphenicol (100%), and amikacin (100%) whereas 100% resistance was observed for penicillin with minimal inhibitory concentration range of 32-256 MUg/mL. PMID- 22085220 TI - Tournefortia sarmentosa extract attenuates acetaminophen-induced hepatotoxicity. AB - CONTEXT: Tournefortia sarmentosa Lam. (Boraginaceae), a Chinese herbal medicine, is commonly used as a detoxicant or anti-inflammatory agent. OBJECTIVE: As acetaminophen (APAP) is a well-known hepatotoxin, we investigated the effect of the aqueous extract of the T. sarmentosa on APAP-induced hepatotoxicity in vivo and in vitro. MATERIALS AND METHODS: Levels of liver function markers serum glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (ALP), inflammatory markers tumor necrosis factor (TNF)-alpha, interleukin (IL)-1b, and IL-6 in serum, and antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as lipid peroxidation were determined. RESULTS: T. sarmentosa significantly reduced the elevated liver function (SGOT, SGPT, and ALP, p < 0.01) and inflammatory markers (TNF-alpha, IL-1beta, and IL-6, p < 0.01) in serum of APAP-intoxicated rats. Malondialdehyde level (p < 0.05) and antioxidant enzyme levels (CAT, SOD, and GPx, p < 0.05) were also reduced in APAP-intoxicated rats treated with T. sarmentosa. Incubation of rat hepatocyte cell line clone-9 cells with APAP reduced cell viability and increased the extent of lipid peroxidation. APAP stimulation also reduced the level of glutathione (GSH) and caused reduction in the activities of the antioxidant enzymes, CAT, SOD, and GPx. Pretreatment of hepatocytes with T. sarmentosa aqueous extract before and during APAP stimulation attenuated the extent of lipid peroxidation, increased cell viability and GSH level, and enhanced the activities of antioxidant enzymes. DISCUSSION AND CONCLUSION: These data suggest that the aqueous extract of T. sarmentosa can prevent APAP-induced hepatotoxicity. PMID- 22085219 TI - rROP2(186-533): a novel peptide antigen for detection of IgM antibodies against Toxoplasma gondii. AB - Toxoplasma gondii infections are prevalent in a wide range of mammalian hosts including humans. Infection in pregnant women may cause the transmission of parasite to the fetus that makes serious problems. IgM antibodies against Toxoplasma (Toxo-IgM) have been believed to be significant indicators for both recently acquired and congenital toxoplasmosis. So far, however, there has not been any recognized protein of T. gondii that specifically reacts to IgM antibodies. Here, an antigen exclusively for detection of IgM antibodies screened by two-dimensional electrophoresis and mass spectrometry has been reported. The study identified 13 Toxoplasma proteins probed by IgG antibodies and one (rhpotry protein 2 [ROP2]) by IgM antibodies with human sera of Toxo-IgM(-)-IgG(+) and IgM(+)-IgG(-), respectively, which had been prescreened by Toxo-IgM and -IgG commercial kits from the suspected cases. Following cloning, expression, and purification of the fragment of ROP2(186-533), an enzyme-linked immunosorbent assay with rROP2(186-533) to measure IgM and IgG antibodies was developed. As a result, 100%(48/48) of sera with Toxo-IgM(+)-IgG(-)showed positive Toxo-IgM but none of them (0%) showed positive Toxo-IgG when rROP2(186-533) was used as antigen. Neither Toxo-IgG nor Toxo-IgM antibodies were found when tested with 59 sera of Toxo-IgM(-)-IgG(+). These results indicate that rROP2(186-533) could be used as an antigen that specifically capture Toxo-IgM antibodies and may have a high potential in the serological diagnosis of both acute acquired and congenital toxoplasmosis. PMID- 22085221 TI - General and cancer mortality in a large cohort of Italian alcoholics. AB - BACKGROUND: The consumption of alcohol is an underappreciated risk factor for a wide range of conditions. Overall, it is associated with high mortality rates and causes approximately 4% of all deaths worldwide. This study aimed to evaluate the general and cancer mortality in a cohort of subjects with alcohol addiction residing in Tuscany (Central Italy). METHODS: Overall, 2,272 alcoholics (1,467 men and 805 women; mean age at first examination 43.8 years +/- 13.0), treated at the Alcohol Centre of Florence in the period April 1985 to September 2001, were followed until the end of the study period (median follow-up: 9.6 years). A total of 21,855 person-years were available for analyses. Expected deaths were estimated by using age, sex, and calendar-specific regional mortality rates. Standardized mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. RESULTS: Six hundred and thirty-six of the 2,272 patients (28.0%) died, yielding an SMR of 5.0 (95% CI: 4.6 to 5.4). The alcoholics had significantly elevated mortality risk from all malignant cancers (SMR = 3.8, 95% CI: 3.3 to 4.4) and a series of specific diseases (infections: SMR = 10.1, 95% CI: 4.8 to 21.1; diabetes: SMR = 3.6, 95% CI: 1.9 to 6.7; immunological system, including AIDS: SMR = 8.1, 95% CI: 4.1 to 16.2; nervous system: SMR = 3.5, 95% CI: 1.9 to 6.4; cardiovascular system: SMR = 2.4, 95% CI: 2.0 to 2.9; respiratory system: SMR = 5.8, 95% CI: 4.2 to 8.0; digestive system: SMR = 26.4, 95% CI: 22.6 to 30.8, including liver cirrhosis (SMR = 40.0, 95% CI: 33.9 to 47.1); violent causes: SMR = 6.6, 95% CI: 5.0 to 8.6). Among malignant cancers, the highest SMRs were found for cancers of the pharynx (SMR = 22.8, 95% CI: 9.5 to 54.8), oral cavity (SMR = 22.2, 95% CI: 13.2 to 37.6), liver (SMR = 13.5, 95% CI: 9.2 to 19.8), and larynx (SMR = 10.7, 95% CI: 5.8 to 19.9). Although women showed higher SMR in comparison with the general population of the area, their overall survival estimates during the follow-up were higher than those for male alcoholics. CONCLUSIONS: This large series of Italian alcoholics showed a significant increase in total and cancer mortality in comparison with the general population, with female alcoholics reporting higher survival rates. PMID- 22085222 TI - Impact of the 2009/2010 influenza A (H1N1) pandemic on trends in influenza hospitalization, diagnostic testing, and treatment. AB - Analysis of a US hospitalization database demonstrated that more influenza patients were hospitalized and the age distribution of hospitalizations was younger during the 2009 (H1N1) influenza A pandemic compared with the three previous influenza seasons. The duration of hospital stay remained stable in all four seasons. A higher proportion of patients was treated with antivirals (P < 0.0001), comprised almost entirely of neuraminidase inhibitors, and the proportion was highest in those with influenza confirmed by diagnostic testing (P < 0.0001). Approximately one-third remained untreated. Young children had the lowest rate of neuraminidase-inhibitor treatment during the 2009 pandemic (P < 0.05). PMID- 22085223 TI - The effect of an atomically deposited layer of alumina on NiO in P-type dye sensitized solar cells. AB - We present a systematic investigation of the fundamental effects of an atomically deposited alumina (AlO(x)H(y)) onto the NiO films in p-type dye-sensitized solar cells (p-DSCs). With P1 as the sensitizing dye and 0.1 M I(2) and 1.0 M LiI in 3 methoxypropionitrile as the electrolyte, one atomic layer deposition (ALD) cycle of alumina was used to achieve a 74% increase in the overall conversion efficiency of a NiO-based DSC. The open circuit voltage of the cells increased from 0.11 to 0.15 V, and the short circuit current density increased from 0.83 to 0.95 mA/cm(2). Adsorption isotherm studies were performed to show that the amount of dye adsorbed on the NiO-alumina film is slightly lower than the amount adsorbed on the nontreated NiO film. The increased J(sc) was therefore assigned to the increased efficiency of carrier collection at the semiconductor-FTO interface. Our study of the photocurrent onset potentials of NiO and NiO-alumina films with the chopped light measurement technique showed no definitive difference in the onset potential values. However, the DSCs based on NiO-alumina showed a higher recombination resistance value from the electrochemical impedance studies and a higher diode ideality factor from the V(oc) versus ln(light intensity) plots as compared to the DSCs based on untreated NiO. It has thus been established that the increase in V(oc) upon alumina treatment arises due to a higher resistance for electron-hole recombination across NiO surface locally. PMID- 22085224 TI - Enhancement of the luminescent properties of a new red-emitting phosphor, Mn2(HPO3)F2, by Zn substitution. AB - The Mn(2)(HPO(3))F(2) phase has been synthesized as single crystals by using mild hydrothermal conditions. The compound crystallizes in the orthorhombic Pnma space group, with unit cell parameters of a = 7.5607(8), b = 10.2342(7), and c = 5.5156(4) A, with Z = 4. The crystal structure consists of a three-dimensional framework formed by alternating (010) layers of [MnO(3)F(3)] octahedra linked up by three connected [HPO(3)] tetrahedra. Luminescence measurements were performed at different temperatures between 10 and 150 K. The 10 K emission spectrum of the octahedrally coordinated Mn(II) cation exhibits a broad band centered at around 615 nm corresponding to the (4)T(1) -> (6)A(1) transition. In order to explore the effect of the Mn(II) concentration and the possibility of enhancing the luminescence properties of the Mn(II) cation in Mn(2)(HPO(3))F(2), different intermediate composition members of the finite solid solution with the general formula (Mn(x)Zn(1-x))(2)(HPO(3))F(2) were prepared and their luminescent properties studied. The magnetic and specific heat behavior of M(2)(HPO(3))F(2) (M = Mn, Fe) have also been investigated. The compounds exhibit a global antiferromagnetic ordering with a spin canting phenomenon detected at approximately 30 K. The specific heat measurements show sharp lambda-type peaks at 29.7 and 33.5 K for manganese and iron compounds, respectively. The total magnetic entropy is consistent with spin S = 5/2 and S = 2 of Mn(II) and Fe(II) cations. PMID- 22085226 TI - Stereoselective vinylation of aryl N-(2-pyridylsulfonyl) aldimines with 1-alkenyl 1,1-heterobimetallic reagents. AB - Vinylation of aryl N-(2-pyridylsulfonyl) aldimines with versatile 1-alkenyl-1,1 borozinc heterobimetallic reagents is disclosed. In situ hydroboration of air stable B(pin)-alkynes followed by chemoselective transmetalation with dimethylzinc and addition to aldimines provides B(pin)-substituted allylic amines in 53-93% yield in a one-pot procedure. The addition step can be followed by either B-C bond oxidation to provide alpha-amino ketones (71-98% yield) or Suzuki cross-coupling to furnish trisubstituted 2-arylated (E)-allylic amines (51-73% yield). PMID- 22085227 TI - Tadalafil once daily and extracorporeal shock wave therapy in the management of patients with Peyronie's disease and erectile dysfunction: results from a prospective randomized trial. AB - Extracorporeal shock wave therapy improves erectile function in patients with Peyronie's disease. However, erectile dysfunction still persists in many cases. We aimed to investigate the effects of extracorporeal shock wave therapy plus tadalafil 5 mg once daily in the management of patients with Peyronie's disease and erectile dysfunction not previously treated. One hundred patients were enrolled in a prospective, randomized, controlled study. Patients were randomly allocated to receive either extracorporeal shock wave therapy alone for 4 weeks (n = 50) or extracorporeal shock wave therapy plus tadalafil 5 mg once daily for 4 weeks (n = 50). Main outcome measures were: erectile function (evaluated through the shortened version of the International Index of Erectile Function), pain during erection (evaluated through a Visual Analog Scale), plaque size, penile curvature and quality of life (evaluated through an internal questionnaire). Follow-up evaluations were performed after 12 and 24 weeks. In both groups, at 12 weeks follow-up, mean Visual Analog Scale score, mean International Index of Erectile Function score and mean quality of life score ameliorated significantly while mean plaque size and mean curvature degree were unchanged. Intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and quality of life score in patients receiving the combination. After 24 weeks, intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and mean quality of life score in patients that received extracorporeal shock wave therapy plus tadalafil. In conclusion extracorporeal shock wave therapy plus tadalafil 5 mg once daily may represent a valid conservative strategy for the management of patients with Peyronie's disease and erectile dysfunction. PMID- 22085229 TI - Strong molecular traffic control effect in TNU-9 zeolite channel topology. AB - Reactivity enhancement in a catalytic zeolite grain through molecular traffic control (MTC) rests on the basic notion that the reactant and product molecules prefer to diffuse along different channels inside the grain and therefore do not mutually hinder their transport in and out of the grain. We investigate the conditions of reactivity enhancement in the presence of MTC for a realistic channel topology that describes the pore structure of a TNU-9 zeolite. We compare the output current of an MTC system with a reference system, which does not show any channel selectivity. For a wide range of reaction rates and for different grain sizes, we find that there is a very significant enhancement of reactivity for the MTC system. This effect remains strong as the grain size increases. The mechanism behind reactivity enhancement is argued to be generic rather than being confined to the particular structure of TNU-9. PMID- 22085228 TI - Brief review of models of ectopic bone formation. AB - Ectopic bone formation is a unique biologic entity--distinct from other areas of skeletal biology. Animal research models of ectopic bone formation most often employ rodent models and have unique advantages over orthotopic (bone) environments, including a relative lack of bone cytokine stimulation and cell-to cell interaction with endogenous (host) bone-forming cells. This allows for relatively controlled in vivo experimental bone formation. A wide variety of ectopic locations have been used for experimentation, including subcutaneous, intramuscular, and kidney capsule transplantation. The method, benefits and detractions of each method are summarized in the following review. Briefly, subcutaneous implantation is the simplest method. However, the most pertinent concern is the relative paucity of bone formation in comparison to other models. Intramuscular implantation is also widely used and relatively simple, however intramuscular implants are exposed to skeletal muscle satellite progenitor cells. Thus, distinguishing host from donor osteogenesis becomes challenging without cell-tracking studies. The kidney capsule (perirenal or renal capsule) method is less widely used and more technically challenging. It allows for supraphysiologic blood and nutrient resource, promoting robust bone growth. In summary, ectopic bone models are extremely useful in the evaluation of bone-forming stem cells, new osteoinductive biomaterials, and growth factors; an appropriate choice of model, however, will greatly increase experimental success. PMID- 22085232 TI - When movies matter: exposure to smoking in movies and changes in smoking behavior. AB - The authors investigated the association between exposure to smoking in movies and the initiation and progression of adolescent smoking over time among 6,522 U.S. adolescents (between the ages of 10 and 14 years, at baseline) in a nationally representative, 4-wave random-digit-dial telephone survey. They conducted a hazard (survival) analysis testing whether exposure to movie smoking and demographic, personality, social, and structural factors predict (a) earlier smoking onset and (b) faster transition to experimental (1-99 cigarettes/lifetime) and established smoking (>100 cigarettes/lifetime). Results suggest that higher exposure to movie smoking is associated with less time to trying cigarettes for the first time (adjusted hazard ratio = 1.66; 95% CI [1.37, 2.01]) but not with faster escalation of smoking behavior following initiation (adjusted hazard ratio = 1.53; 95% CI [0.84, 2.79]). In contrast, age, peer smoking, parenting style, and availability of cigarettes in the home were predictors of earlier onset and faster transition to established smoking. Thus, the authors concluded that the effect of exposure to mass-mediated images of smoking in movies may decline once adolescents have started to smoke, whereas peers and access to tobacco remain influential. PMID- 22085230 TI - Systemic responses of preterm newborns with presumed or documented bacteraemia. AB - AIM: To compare the frequency of elevated concentrations of inflammation-related proteins in the blood of infants born before the 28th week of gestation who had documented bacteraemia and those who had presumed (antibiotic-treated but culture negative) bacteraemia to those who had neither. METHODS: The subjects of this study are the 868 infants born at 14 institutions for whom information about protein measurements on at least two of the three protocol days (days 1, 7, and 14) was available and who did not have Bell stage 3 necrotizing enterocolitis or isolated bowel perforation, which were strongly associated with bacteraemia in this sample. RESULTS: Newborns with presumed early (week 1) bacteraemia had elevated concentrations of only a few inflammation-related proteins, while those who had presumed late (weeks 2-4) bacteraemia did not have any elevations. In contrast, newborns who had documented early bacteraemia had a moderately strong signal, while those who had documented late bacteraemia had a stronger signal with more protein concentrations elevated on two separate occasions a week apart. CONCLUSIONS: Culture-confirmed early and late bacteraemia are accompanied/followed by systemic inflammatory responses not seen with presumed early and late bacteraemia. PMID- 22085233 TI - Cardiovascular comorbidity and treatment regret in men with recurrent prostate cancer. AB - Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? Treatment regret can have an adverse impact on a patient's overall outlook and has been associated with a poorer global quality of life. Understanding predictors of regret can help clinicians better counsel patients about their treatments so that later regret can be avoided. In previous studies, regret has been associated with lesser educational attainment, non-White race, greater post-treatment declines in sexual function and systemic symptoms. The present study found that, among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to regret their treatment choice than men without cardiovascular comorbidity. This study highlights the growing importance of considering comorbidity when counselling patients about prostate cancer treatment options, and provides a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer. OBJECTIVE: * To determine whether cardiovascular comorbidity is associated with increased treatment regret among men with recurrent prostate cancer. METHODS: * The study cohort comprised 795 men in the Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma (COMPARE) registry who experienced biochemical recurrence at a median (interquartile range) of 5.5 (2.8-9.1) years after prostatectomy (n= 410), external beam radiation therapy (n= 237), brachytherapy (n= 124) or primary androgen deprivation therapy (n= 24). * Multivariable logistic regression analysis was used to determine whether cardiovascular comorbidity was associated with treatment regret. * Cardiovascular comorbidity, which included myocardial infarction, congestive heart failure, angina, diabetes, stroke or circulation problems, was defined using a validated two-question screening process after adjusting for sociodemographic and treatment factors and post-treatment bladder and bowel toxicity. RESULTS: * Of 795 men, 14.8% reported regret. * Men with cardiovascular comorbidity were more likely to experience post-therapy bowel toxicity (P= 0.022). * In the adjusted multivariable model, the factors associated with increased treatment regret were: cardiovascular comorbidity (adjusted odds ratio [AOR]= 1.52 [95% CI:1.00-2.31], P= 0.048); younger age (AOR: 0.97 [95% CI 0.94-0.99] per year increase in age, P= 0.019); and bowel toxicity after treatment (AOR 1.58 [95% CI 1.03-2.43], P= 0.038). CONCLUSIONS: * Among men with recurrent prostate cancer, those with cardiovascular comorbidity were >50% more likely to experience treatment regret than men without cardiovascular comorbidity. * These data provide a rationale for men with cardiovascular comorbidity to give additional consideration to active surveillance for their newly diagnosed prostate cancer. PMID- 22085235 TI - A highly C70 selective shape-persistent rectangular prism constructed through one step alkyne metathesis. AB - Dynamic covalent chemistry (DCC) provides an intriguing and highly efficient approach for building molecules that are usually thermodynamically favored. However, the DCC methods that are efficient enough to construct large, complex molecules, particularly those with three-dimensional (3-D) architectures, are still very limited. Here, for the first time, we have successfully utilized alkyne metathesis, a highly efficient DCC approach, to construct the novel 3-D rectangular prismatic molecular cage COP-5 in one step from a readily accessible porphyrin-based precursor. COP-5 consists of rigid, aromatic porphyrin and carbazole moieties as well as linear ethynylene linkers, rendering its shape persistent nature. Interestingly, COP-5 serves as an excellent receptor for fullerenes. It forms 1:1 complexes with C(60) and C(70) with association constants of 1.4 * 10(5) M(-1) (C(60)) and 1.5 * 10(8) M(-1) (C(70)) in toluene. This represents one of the highest binding affinities reported so far for purely organic fullerene receptors. COP-5 shows an unprecedented high selectivity in binding C(70) over C(60) (K(C70)/K(C60) > 1000). Moreover, the binding between the cage and fullerene is fully reversible under the acid-base stimuli, thus allowing successful separation of C(70) from a C(60)-enriched fullerene mixture (C(60)/C(70), 10/1 mol/mol) through the "selective complexation-decomplexation" strategy. PMID- 22085236 TI - Alternative regimens for endometrial protection ? Where are we now? PMID- 22085237 TI - Physical function in overweight postmenopausal women. PMID- 22085241 TI - Computational haemodynamics in two idealised cerebral wide-necked aneurysms after stent placement. AB - Endovascular stents are being commonly used to treat cerebral wide-necked aneurysms recently. The effect of a stent placed in the parent artery is not only to protect the parent artery from occlusion, due to extension of coils and thrombosis, but also to act as flow diverter to vary the haemodynamics in the aneurysm. In this article, two idealised cerebral wide-necked aneurysms were created, one was sidewall aneurysm with curved parent vessel and the other was terminal aneurysm with the bifurcated parent vessel. The plexiglass models of the two aneurysms were 'treated' with commercial porous intravascular stents. The stented physical models were scanned by Micro-CT and the numerical models of the two idealised cerebral wide-necked aneurysms after stent placement were constructed from the scanned image files. The pulsatile flow of non-Newtonian fluid inside the models was simulated by using computational fluid dynamics package. From the simulated flow dynamics, various haemodynamic characteristics such as velocity contours, wall shear stress and oscillatory shear index (OSI) were computed. The velocity of the jet entering the sacs reduced after stent was deployed across the necks of both sidewall and terminal aneurysms; the wall shear stress on the distal neck of sidewall aneurysm reduced, the wall shear stress on the dome of the terminal aneurysm increased and the OSI on the dome of the terminal aneurysm reduced. Therefore, stent placement not only promotes thrombus formation in both aneurysm models but also reduces the regrowth risk of the sidewall aneurysm and the rupture risk of the terminal aneurysm. PMID- 22085242 TI - Are respiratory complications common causes of death in inflammatory myopathies? An autopsy study. AB - BACKGROUND AND OBJECTIVE: Polymyositis (PM) and dermatomyositis (DM) are idiopathic inflammatory myopathies that are associated with a variety of clinical manifestations including pulmonary complications. The objective of the present study was to determine the causes of deaths in this complex patient population. METHODS: A computer-assisted search of medical and autopsy records identified a total of 39 patients with either PM or DM who underwent an autopsy at the Mayo Clinic (Rochester, MN, USA) over a 29-year period from 1 January 1981 to 31 December 2009. The immediate causes of death along with contributing causes were determined by reviewing all available clinical data and autopsy findings. We also analysed the discordance between ante-mortem clinical diagnoses provided by clinicians and the final diagnosis by the post-mortem analysis. RESULTS: Respiratory (33%), infectious (28%) and cardiovascular diseases (26%) accounted for the majority of immediate causes of death. Acute exacerbation of chronic interstitial lung disease (15%) and bronchopneumonia (15%) were the most common specific causes. Immediate cause of death was not suspected in nearly one third of cases and included bronchopneumonia, sepsis, acute myocardial infarction, aspiration pneumonia, pulmonary embolism, aortic stenosis, mycotic aneurysm rupture and acute haemoperitoneum. CONCLUSIONS: We conclude that pulmonary injury is the immediate cause of death in one third of patients with PM/DM; acute exacerbation of chronic interstitial lung disease and bronchopneumonia were the most common specific causes. Immediate cause of death was not established ante mortem in nearly one third of cases, and some of these causes were treatable. PMID- 22085243 TI - Influenza neuraminidase. AB - Influenza neuraminidase is the target of two licensed antivirals that have been very successful, with several more in development. However, neuraminidase has been largely ignored as a vaccine target despite evidence that inclusion of neuraminidase in the subunit vaccine gives increased protection. This article describes current knowledge on the structure, enzyme activity, and antigenic significance of neuraminidase. PMID- 22085244 TI - A source of ultrasensitivity in the glutamine response of the bicyclic cascade system controlling glutamine synthetase adenylylation state and activity in Escherichia coli. AB - Glutamine synthetase (GS) activity in Escherichia coli is regulated by reversible adenylylation, brought about by a bicyclic system comprised of uridylyltransferase/uridylyl-removing enzyme (UTase/UR), its substrate, PII, adenylyltransferase (ATase), and its substrate, GS. The modified and unmodified forms of PII produced by the upstream UTase/UR-PII cycle regulate the downstream ATase-GS cycle. A reconstituted UTase/UR-PII-ATase-GS bicyclic system has been shown to produce a highly ultrasensitive response of GS adenylylation state to the glutamine concentration, but its composite UTase/UR-PII and ATase-GS cycles displayed moderate glutamine sensitivities when examined separately. Glutamine sensitivity of the bicyclic system was significantly reduced when the trimeric PII protein was replaced by a heterotrimeric form of PII that was functionally monomeric, and coupling between the two cycles was different in systems containing wild-type or heterotrimeric PII. Thus, the trimeric nature of PII played a role in the glutamine response of the bicyclic system. We therefore examined regulation of the individual AT (adenylylation) and AR (deadenylylation) activities of ATase by PII preparations with various levels of uridylylation. AR activity was affected in a linear fashion by PII uridylylation, but partially modified wild-type PII activated the AT much less than expected based on the extent of PII modification. Partially modified wild-type PII also bound to ATase less than expected based upon the fraction of modified subunits. Our results suggest that the AT activity is only bound and activated by completely unmodified PII and that this design is largely responsible for ultrasensitivity of the bicyclic system. PMID- 22085245 TI - Biomass allocation to leaves, stems and roots: meta-analyses of interspecific variation and environmental control. AB - We quantified the biomass allocation patterns to leaves, stems and roots in vegetative plants, and how this is influenced by the growth environment, plant size, evolutionary history and competition. Dose-response curves of allocation were constructed by means of a meta-analysis from a wide array of experimental data. They show that the fraction of whole-plant mass represented by leaves (LMF) increases most strongly with nutrients and decreases most strongly with light. Correction for size-induced allocation patterns diminishes the LMF-response to light, but makes the effect of temperature on LMF more apparent. There is a clear phylogenetic effect on allocation, as eudicots invest relatively more than monocots in leaves, as do gymnosperms compared with woody angiosperms. Plants grown at high densities show a clear increase in the stem fraction. However, in most comparisons across species groups or environmental factors, the variation in LMF is smaller than the variation in one of the other components of the growth analysis equation: the leaf area : leaf mass ratio (SLA). In competitive situations, the stem mass fraction increases to a smaller extent than the specific stem length (stem length : stem mass). Thus, we conclude that plants generally are less able to adjust allocation than to alter organ morphology. PMID- 22085246 TI - Hydrogen-bonded inclusion compounds with reversed polarity: anionic metal complexes and cationic organic linkers. AB - Synthesized and structurally characterized is a new series of soft-host frameworks assembled by charge-assisted hydrogen bonds between an anionic metal complex (MC) and cationic organic linkers (OL), specifically [Co(en)(ox)(2)](-) and diprotonated 4,4'-bipyridinium (H(2)bpy) or 1,2-bis(4-pyridinium)ethylene (H(2)bpye). While frameworks built of cationic complexes and anionic organic linkers are already well-known, the seven new compounds described here represent the first series of frameworks with reversed polarity, that is, made of anionic complexes and cationic organic linkers. The compounds have a general formula [OL][MC](2).n(guest), where the guest molecules 4,4'-biphenol (bp), 4 methoxyphenol (mp), 1,4-dimethoxybenzene (dmb), 1,6-dimethoxynaphtalene (dmn), and 4-nitroanisole (na). Structurally the compounds can be described as pillared layer frameworks with layers constructed of MC anions and linked together by hydrogen-bonded cationic OL pillars. The guest molecules occupy the galleries between the pillars while their steric, electronic, and pi-pi and hydrogen bonding capabilities influence the overall structure of the soft frameworks. PMID- 22085247 TI - Effect of cis and trans double bonds on conformational disordering of the hydrocarbon chain of lipid, unsaturated monoacylglycerols, in the lamellar phase of a binary system with water. AB - To clarify the influence of cis and trans double bonds on conformational disordering of unsaturated hydrocarbon-chain of lipids in bilayer formed in the binary system with water, calorimetric study was conducted for systems of unsaturated monoacylglycerols; monoolein (MO), monovaccenin (MV), and monoelaidin (ME). Heat capacities of the binary systems were measured by adiabatic calorimetry. The observed entropies of transition (Delta(trs)S) from lamellar phase (L(alpha)) to fluid isotropic (FI) phase are very small and depend on lipids: Delta(trs)S of MO/water, MV/water, and ME/water were ca. 0.8 J K(-1) (mol of lipid) (-1), ca. 0.9 J K(-1) (mol of lipid) (-1), and ca. 0.4 J K(-1) (mol of lipid) (-1), respectively. These show that the conformational disordering of the hydrocarbon chain over gauche and trans conformations is suppresed in L(alpha) phase. Through the comparison of Delta(trs)S among the binary systems, the suppresed conformational disordering of hydrocarbon chain in the bilayer is discussed. PMID- 22085248 TI - Palladium-catalyzed synthesis of 4-aminophthalazin-1(2H)-ones by isocyanide insertion. AB - Palladium-catalyzed cross-coupling of a wide range of substituted o (pseudo)halobenzoates and hydrazines with isocyanide insertion followed by lactamization efficiently affords 4-aminophthalazin-1(2H)-ones that are difficult to obtain regioselectively by classical methods. PMID- 22085249 TI - Use of hyperbaric oxygen in traumatic brain injury: retrospective analysis of data of 20 patients treated at a tertiary care centre. AB - Traumatic brain injury (TBI) related impact results in a permanent need for help in performing daily activities. Standard treatment consists of removing the cause, restore perfusion, support metabolic requirement and limit inflammatory and oxidative damage. Hyperbaric oxygen therapy (HBOT) is one such newer promising treatment that enhances neurological recovery to some extent. HBOT is intermittent inhalation of 100% oxygen at greater than normal atmospheric pressure and is internationally accepted for its role in well-defined indications. It is hypothesised that HBO has a role in reviving 'idling neurons', also called the ischemic penumbra defined as area of reduced cerebral blood flow, abolished synaptic activity but preserved structural integrity. We carried out a retrospective analysis of medical records of 20 patients of TBI who had been treated with HBOT in addition to standard management. These were placed in Group A (test group) and received at least 30 sessions of HBO along with standard treatment. The patients were assessed along the Disability Rating Scale (DRS), Glasgow coma scale (GCS) and Rancho Los Amigos Scale (RLAS). Another 20 patients of TBI, matched in age and severity of brain injury, who received standard treatment but not HBOT, were selected as the control group (Group B). Assessment on the DRS showed maximum improvement in patients with scores of 22-24 (vegetative state).The percentage of patients in the test group fell from 45% to 5% whereas only 20% patients in Group B had similar progress. After the treatment, a significantly higher proportion of HBOT treated subjects showed a good response in cognitive functions, as measured by RLA. In group A, 90% patients had a score of <= 3 and in Group B 95% had a similar score, which improved to >= 3 in 60% patients versus 30% patients respectively. In both groups maximum patients are in 1-6 months post-injury category and within the groups this category showed the greatest recovery, with a greater improvement in the test group as compared to control group. PMID- 22085250 TI - Post-operative spinal subdural extra-arachnoid hygroma causing cauda equina compression: a report of two cases. AB - We present two cases of symptomatic, post-lumbar surgery cauda equina compression due to formation of a dissecting subdural extra-arachnoid cerebrospinal fluid (CSF) collection (hygroma) under tension. In both cases, a small inadvertent durotomy was sustained during the initial surgery. Surgical re-exploration confirmed a tension subdural extra-arachnoid hygroma due to one-way flow of CSF through a pinhole puncture in the arachnoid. The mechanism and clinico radiological features of this rare post-operative complication are discussed. PMID- 22085251 TI - The Goldilocks principle and antibiotic resistance in bacteria. AB - We have designed and fabricated a microecology to mimic a naturally occurring bacterial culture, which includes the stress gradient, metapopulation, and cellular motility. In this microecology, we show that it is possible to fix the resistance to the mutagenic antibiotic Ciprofloxacin in wild-type Escherichia coli within 10 h. We found the evolution of resistance is further accelerated in microecology if bacteria have already acquired the phenotype of growth advantage at the stationary phase (GASP). PMID- 22085252 TI - Antinociceptive and anti-inflammatory effects of olive oil (Olea europeae L.) in mice. AB - CONTEXT: Olive [Olea europaea L. (Oleaceae)] is a long-lived evergreen tree that is widespread in different parts of the world. OBJECTIVE: Olive oil has been reported to relieve pain; however, there is still insufficient data in the literature on the subject. Thus, it is considered worthwhile investigating the antinociceptive and anti-inflammatory effects of olive oil in adult male Balb/C mice. MATERIALS AND METHODS: The antinociceptive effects were studied using formalin, hot plate and writhing tests. The acute anti-inflammatory effects of olive oil in mice were studied using xylene ear edema test. Olive oil (1, 5 and 10 ml/kg body wt.) was injected intraperitoneally. Intact animals served as controls. RESULTS: Our results showed that the olive oil only decreased the second phase of formalin-induced pain. In the hot plate test, olive oil did not raise the pain threshold over the 60 min duration of the test. Olive oil exhibited antinociceptive activity against writhing-induced pain by acetic acid. In the xylene ear edema test, olive oil showed significant anti-inflammatory activity in the mice. DISCUSSION AND CONCLUSION: The present data indicated that olive oil has antinociceptive and anti-inflammatory effects in mice but further investigation of these effects is required to elucidate the mechanism(s) involved in analgesic and anti-inflammatory effects of Olea europaea oil. PMID- 22085253 TI - Compaction and transport properties of newly replicated Caulobacter crescentus DNA. AB - Upon initiating replication of the Caulobacter chromosome, one copy of the parS centromere remains at the stalked pole; the other moves to the distal pole. We identified the segregation dynamics and compaction characteristics of newly replicated Caulobacter DNA during transport (highly variable from cell to cell) using time-lapse fluorescence microscopy. The parS centromere and a length (also highly variable) of parS proximal DNA on each arm of the chromosome are segregated with the same relatively slow transport pattern as the parS locus. Newly replicated DNA further than about 100 kb from parS segregates with a different and faster pattern, while loci at 48 kb from parS segregate with the slow pattern in some cells and the fast pattern in others. The observed parS proximal DNA compaction characteristics have scaling properties that suggest the DNA is branched. HU2-deletion strains exhibited a reduced compaction phenotype except near the parS site where only the DeltaHU1DeltaHU2 double mutant had a compaction phenotype. The chromosome shows speed-dependent extension during translocation suggesting the DNA polymer is under tension. While DNA segregation is highly reliable and succeeds in virtually all wild-type cells, the high degree of cell to cell variation in the segregation process is noteworthy. PMID- 22085255 TI - Locally advanced prostate cancer: a population-based study of treatment patterns. AB - Study Type--Therapy (practice patterns). Level of Evidence 2b. What's known on the subject? And what does the study add? The treatment of locally advanced prostate cancer varies widely even though there is level one evidence supporting the use of multimodality therapy as compared with monotherapy. This study defines treatment patterns of locally advanced prostate cancer within the United States and identifies predicators of who receives multimodality therapy rather than monotherapy. OBJECTIVE: * To identify treatment patterns and predictors of receiving multimodality therapy in patients with locally advanced prostate cancer (LAPC). PATIENTS AND METHODS: * The cohort comprised patients >=66 years with clinical stage T3 or T4 non-metastatic prostate cancer diagnosed between 1998 and 2005 identified from the Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare claims. * Treatments were classified as radical prostatectomy (RP), radiation therapy (RT) and androgen deprivation therapy (ADT) received within 6 and 24 months of diagnosis. * We assessed trends over time and used multivariable logistic regression to identify predictors of multimodality treatment. RESULTS: * Within the first 6 months of diagnosis, 1060 of 3095 patients (34%) were treated with a combination of RT and ADT, 1486 (48%) received monotherapy (RT alone, ADT alone or RP alone), and 461 (15%) received no active treatment. * The proportion of patients who received RP increased, exceeding 10% in 2005. * Use of combined RT and ADT and use of ADT alone fluctuated throughout the study period. * In all 6% of patients received RT alone in 2005. * Multimodality therapy was less common in patients who were older, African American, unmarried, who lived in the south, and who had co-morbidities or stage T4 disease. CONCLUSIONS: * Treatment of LAPC varies widely, and treatment patterns shifted during the study period. * The slightly increased use of multimodality therapy since 2003 is encouraging, but further work is needed to increase combination therapy in appropriate patients and to define the role of RP. PMID- 22085254 TI - An in vivo characterization of trophic factor production following neural precursor cell or bone marrow stromal cell transplantation for spinal cord injury. AB - Cellular transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant elevation of nerve growth factor (NGF), leukemia inhibitory factor (LIF), insulin-like growth factor 1 (IGF-1), and transforming growth factor-beta1 (TGF-beta1), and lower expression of vascular endothelial growth factor isoform A (VEGF-A) and platelet-derived growth factor-A (PDGF-A). Transplantation of NPCs led to modest changes in trophin expression, and the co-administration of intrathecal trophins resulted in significant elevation of the neurotrophins, glial-derived neurotrophic factor (GDNF), LIF, and basic fibroblast growth factor (bFGF). BMSCs transplantation upregulated NGF, LIF, and IGF-1. NPCs isolated after transplantation into the injured spinal cord expressed the neurotrophins, ciliary neurotrophic factor (CNTF), epidermal growth factor (EGF), and bFGF at higher levels than host cord. These data show that trophin expression in the spinal cord is influenced by injury and cell transplantation, particularly when combined with intrathecal trophin infusion. Trophins may contribute to the benefits associated with cell based repair strategies for spinal cord injury. PMID- 22085256 TI - Neurodevelopmental outcome in full-term newborns with refractory neonatal seizures. AB - AIM: This retrospective study describes the prognosis of full-term newborns with refractory neonatal seizures, comparing the need for treatment with two versus three or more antiepileptic drugs. METHODS: We reviewed our database (January 2002-December 2007) to include newborns with refractory neonatal seizures and abnormal electroencephalogram. Group A consisted of 17 newborns with two antiepileptic drugs. Group B consisted of 29 newborns with three or more antiepileptic drugs. Outcome was determined at 2 years of age using the Dutch Bayley Scales of Infant Development or a neurodevelopmental classification scheme. RESULTS: Group A and group B were comparable regarding to a variety of demographic and aetiologic factors. Thirteen newborns died before 2 years of age and one was lost to follow-up. Normal development at 2 years of age was found in 50% and 5% for group A and B, respectively. Severe neurodevelopmental delay at 2 years of age was found in 30% and 68% for group A and B, respectively. CONCLUSION: The number of antiepileptic drugs probably reflects increased seizure burden and is--in that way--related to poor outcome. This may be useful information for early prediction of adverse neurological outcome in the first days of life. PMID- 22085257 TI - Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis. AB - PURPOSE: Long-term therapy with antiepileptic drugs (AEDs) has been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. We compared the long-term effects of monotherapy using different categories of AEDs on markers of vascular risk and the atherosclerotic process. METHODS: One hundred sixty adult patients who were receiving AED monotherapy, including two enzyme-inducers (carbamazepine, CBZ; and phenytoin, PHT), an enzyme-inhibitor (valproic acid, VPA), and a noninducer (lamotrigine, LTG) for more than 2 years, and 60 controls were enrolled in this study. All study participants received measurement of common carotid artery (CCA) intima media thickness (IMT) by B-mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index, and serum lipid profile or levels of total homocysteine (tHcy), folate, uric acid, fasting blood sugar, high sensitivity C-reactive protein (hs-CRP), or thiobarbituric acid reactive substances (TBARS). KEY FINDINGS: Long-term monotherapy with older generation AEDs, including CBZ, PHT, and VPA, caused significantly increased CCA IMT in patients with epilepsy. After adjustment for the confounding effects of age and gender, the CCA IMT was found to be positively correlated with the duration of AED therapy. Patients with epilepsy who were taking enzyme-inducing AED monotherapy (CBZ, PHT) manifested disturbances of cholesterol, tHcy or folate metabolism, and elevation of the inflammation marker, hs-CRP. On the other hand, patients on enzyme-inhibiting AED monotherapy (VPA) exhibited an increase in the levels of uric acid and tHcy, and elevation of the oxidative marker, TBARS. However, no significant alterations in the markers of vascular risk or CCA IMT were observed in patients who received long-term LTG monotherapy. SIGNIFICANCE: Patients with epilepsy who were receiving long-term monotherapy with CBZ, PHT, or VPA exhibited altered circulatory markers of vascular risk that may contribute to the acceleration of the atherosclerotic process, which is significantly associated the duration of AED monotherapy. This information offers a guide for the choice of drug in patients with epilepsy who require long-term AED therapy, particularly in aged and high-risk individuals. PMID- 22085258 TI - Hood entry coefficients of compound exhaust hoods. AB - A traditional method for assessing the flow rate in ventilation systems is based on multiple readings of velocity or velocity pressure (VP) (usually 10 or 20 points) taken in ductwork sections located away from fittings (> seven * diameters of straight duct). This study seeks to eliminate the need for a multiple-point evaluation and replace it with a simplified method that requires only a single measurement of hood static pressure (SP(h)) taken at a more accessible location (< three * diameters of straight duct from the hood entry). The SP(h) method is widely used for the assessment of flow rate in simple hoods. However, industrial applications quite often use compound hoods that are regularly of the slot/plenum type. For these hoods, a "compound coefficient of entry" has not been published, which makes the use of the hood static pressure method unfeasible. This study proposes a model for the computation of a "compound coefficient of entry" and validates the use of this model to assess flow rate in two systems of well-defined geometry (multi-slotted/plenum and single slotted/tapered or "fish-tail" types). When using a conservative value of the slot loss factor (1.78), the proposed model yielded an estimate of the volumetric flow rate within 10% of that provided by a more comprehensive method of assessment. The simplicity of the hood static pressure method makes it very desirable, even in the upper range of experimental error found in this study. PMID- 22085259 TI - Neonatal respiratory consequences from water birth. AB - AIM: Differentiating features were sought for respiratory distress after water birth versus air birth in term low-risk babies. Clinical and X-ray features were to be assessed to determine if the disease processes could be differentiated. METHODS: Review of case records and X-rays over a 7-year period for all admitted babies with respiratory distress after water birth and a similar group of babies with respiratory distress after air birth. RESULTS: There were 14 water birth babies and 24 air birth babies in the study. The water birth babies showed greater acidosis, greater requirement for ventilation, greater requirement for nitric oxide treatment and greater time to establish feeding. The X-rays could not be reliably allocated to the correct group, but the water birth X-rays were judged to have more severe changes than the air birth babies. CONCLUSION: In low risk babies with respiratory distress, water birth is associated with a greater level of respiratory morbidity than seen after air birth. PMID- 22085260 TI - Total synthesis of the potent androgen receptor antagonist (-)-arabilin: a strategic, biomimetic [1,7]-hydrogen shift. AB - The first total synthesis of (-)-arabilin, a Streptomyces metabolite that inhibits hormone activation of the androgen receptor, has been completed. The key step, a [1,7]-hydrogen shift, establishes the enol ether-containing skipped tetraene substructure. This nonenzymatic pericyclic reaction is considered to be biomimetic. PMID- 22085261 TI - The relationship of leukocyte anisocytosis to holotranscobalamin, a marker of cobalamin deficiency. AB - INTRODUCTION: After measurement of the mean volumes of leukocyte subpopulations as well as the distribution widths (DW) of these volumes has become available, we investigated whether such morphometric leukocyte parameters are associated with a commonly used marker of cobalamin deficiency, i.e., holotranscobalamin (HoloTC). Further, we determined reference intervals for these parameters in an elderly population. METHODS: Consecutive subjectively healthy and volunteering individuals >=60 years were included. Using the UniCel DxH 800 Coulter Cellular Analysis System MoMV, mean neutrophil volume (NeMV), mean lymphocyte volume (LyMV), monocyte anisocytosis (MoV-DW), neutrophil anisocytosis (NeV-DW), and lymphocyte anisocytosis (LyV-DW) were assessed together with other parameters including HoloTC. RESULTS: A total of 150 individuals were included in the study. Reference intervals were not dependent on age and gender. MoV-DW (P = 0.002) and NeV-DW (P = 0.02) were significantly lower, and LyMV was significantly higher (P = 0.04) in participants with a HoloTC concentration <28 pm. In contrast, MCV, MoMV, NeMV, and LyV-DW were not associated with HoloTC concentrations. The area under the curve (AUC) in the receiver operating characteristic analysis for detecting a HoloTC <28 pm was 0.81 [95% confidence interval (CI) (0.73, 0.87)] for MoV-DW and 0.73 (0.66, 0.80) for NeV-DW. CONCLUSION: In this collective of subjectively healthy elderly individuals, monocyte anisocytosis, neutrophil anisocytosis and mean lymphocyte volume were associated with decreased HoloTC. PMID- 22085263 TI - Observations of PDDTT subject to thermal treatment: correlation between performance and order. AB - We show that polybis(thienyl)thienodia-thiazolethiophene (PDDTT), a high performance semiconducting polymer for photodetectors and field-effect transistors, has strong performance dependence on annealing temperature. An unprecedented increase of 3 orders of magnitude is observed in both transistor and photoconductive properties. XRD and AFM evidence points to increased ordering in PDDTT films with annealing. This correlation highlights the importance that order has in determining performance in PDDTT and has possible implications in the design of polymers. PMID- 22085262 TI - Slow motions in the hydrophobic core of chicken villin headpiece subdomain and their contributions to configurational entropy and heat capacity from solid-state deuteron NMR measurements. AB - We have investigated microsecond to millisecond time scale dynamics in several key hydrophobic core methyl groups of chicken villin headpiece subdomain protein (HP36) using a combination of single-site labeling, deuteron solid-state NMR line shape analysis, and computational modeling. Deuteron line shapes of hydrated powder samples are dominated by rotameric jumps and show a large variability of rate constants, activation energies, and rotameric populations. Site-specific activation energies vary from 6 to 38 kJ/mol. An additional mode of diffusion on a restricted arc is significant for some sites. In dry samples, the dynamics is quenched. Parameters of the motional models allow for calculations of configurational entropy and heat capacity, which, together with the rate constants, allow for observation of interplay between thermodynamic and kinetic picture of the landscape. Mutations at key phenylalanine residues at both distal (F47L&F51L) and proximal (F58L) locations to a relatively rigid side chain of L69 have a pronounced effect on alleviating the rigidity of this side chain at room temperature and demonstrate the sensitivity of the hydrophobic core environment to such perturbations. PMID- 22085264 TI - Self-assembly of polydeoxyadenylic acid studied at the single-molecule level. AB - The investigation on the self-assembly of polydeoxyadenylic acid (poly(dA)) is highly important to fully understand its biological function and for its application in the field of nanotechnology. Using the fluorescence resonance energy transfer (FRET) technique, we report investigations for the self-assembly of adenine oligomers induced by pH and coralyne binding at the single-molecule level and in the bulk phase. Results presented here show that A-motif 1 (Alexa488 5'-(dA)(20)-3'-Cy5-5'-(dA)(20)-3'-Alexa488) forms the wire-type duplex at acidic pH, whereas the same conformation of A-motif 2 (Alexa488-5'-(dA)(20)-3'-Cy5-3' (dA)(20)-5'-Alexa488) is induced by coralyne binding at neutral pH. These results indicate that poly(dA) at acidic pH forms a right-handed helical duplex with parallel-mannered chains, whereas the coralyne-poly(dA) binding induces a stable antiparallel duplex. Furthermore, we found that the antiparallel duplex of poly(dA) formed by coralyne binding has a rather extended and less twisted structure as compared to the parallel duplex of poly(dA) formed at acidic pH. On the other hand, from dilution experiments, we found that the parallel duplex formed at acidic pH is converted to "S-form", which has the single-stranded structure with short intramolecular double-stranded regions formed by intramolecular A:A base pairing, while the A-motif-coralyne assembly is dissociated into single strands below a certain concentration. The formation of S form with a short intramolecular double-stranded region formed at acidic pH and very low concentration is confirmed by the quantitative analysis of FCS curve to measure the hydrodynamic radius of a molecule. PMID- 22085265 TI - Reactivities of superoxide and hydroperoxyl radicals with disubstituted cyclic nitrones: a DFT study. AB - The unique ability of nitrone spin traps to detect and characterize transient free radicals by electron paramagnetic resonance (EPR) spectroscopy has fueled the development of new spin traps with improved properties. Among a variety of free radicals in chemical and biological systems, superoxide radical anion (O(2)(*-)) plays a critical role as a precursor to other more oxidizing species such as hydroxyl radical (HO(*)), peroxynitrite (ONOO(-)), and hypochlorous acid (HOCl), and therefore the direct detection of O(2)(*-) is important. To overcome the limitations of conventional cyclic nitrones, that is, poor reactivity with O(2)(*-), instability of the O(2)(*-) adduct, and poor cellular target specificity, synthesis of disubstituted nitrones has become attractive. Disubstituted nitrones offer advantages over the monosubstituted ones because they allow bifunctionalization of spin traps, therefore accommodating all the desired spin trap properties in one molecular design. However, because of the high number of possible disubstituted analogues as candidate, a systematic computational study is needed to find leads for the optimal spin trap design for biconjugation. In this paper, calculation of the energetics of O(2)(*-) and HO(2)(*) adduct formation from various disubstituted nitrones at PCM/B3LYP/6 31+G(d,p)//B3LYP/6-31G(d) level of theory was performed to determine the most favorable disubstituted nitrones for this reaction. In addition, our results provided general trends of radical reactivity that is dependent upon but not exclusive to the charge densities of nitronyl-C, the position of substituents including stereoselectivities, and the presence of intramolecular H-bonding interaction. Unusually high exoergic DeltaG(298K,aq)'s for O(2)(*-) and HO(2)(*) adduct formation were predicted for (3S,5S)-5-methyl-3,5-bis(methylcarbamoyl)-1 pyrroline N-oxide (11-cis) and (4S,5S)-5-dimethoxyphosphoryl-5-methyl-4 ethoxycarbonyl-1-pyrroline N-oxide (29-trans) with DeltaG(298K,aq) = -3.3 and 9.4 kcal/mol, respectively, which are the most exoergic DeltaG(298K,aq) observed thus far for any nitrone at the level of theory employed in this study. PMID- 22085267 TI - Interactions of amines with silicon species in undersaturated solutions leads to dissolution and/or precipitation of silica. AB - The biogeochemical silicon cycle is the focus for many researchers studying the dissolution of silicon species from quartz, amorphous, and biogenic silica. Furthermore, the precipitation of biogenic silica by diatoms, radiolarian, sponges, and plants is also a popular focus for research. The ornate silica structures created by these species has attracted interest from biomaterial scientists and biochemists who have studied mineral formation in an attempt to understand how biogenic silica is formed, often in the presence of proteins and long chain polyamines. This article is at the interface of these seemingly distinct research areas. Here we investigate the effect of a range of amines in globally undersaturated silicon environments. Results are presented on the effect of amine-containing molecules on the formation of silica from undersaturated solutions of orthosilicic acid and globally undersaturated silicon environments. We sought to address two questions: can silica be precipitated/harvested from undersaturated solutions, and can we identify the silicon species that are most active in silica formation? We demonstrate that none of the bioinspired additives investigated here (e.g., poly(allylamine hydrochloride), pentaethylenehexamine, and propylamines) have any influence on orthosilicic acid at undersaturated concentrations. However, under globally undersaturated silicon concentrations, small molecules and polymers containing amine groups were able to interact with oligomers of silicic acid to either generate aggregated materials that can be isolated from solution or increase rates of oligomer dissolution back to orthosilicic acid. Additional outcomes of this study include an extended understanding of how polyelectrolytes and small molecules can promote and/or inhibit silica dissolution and a new method to explore how (bio)organic molecules interact with a forming mineral phase. PMID- 22085266 TI - Beta-xylosidase activity of a GH3 glucosidase/xylosidase from yak rumen metagenome promotes the enzymatic degradation of hemicellulosic xylans. AB - AIMS: To characterize the duel activities of a glycosyl hydrolase family 3 beta glucosidase/xylosidase from rumen bacterial metagenome and to investigate the capabilities of its beta-d-xylosidase activities for saccharification of hemicellulosic xylans. METHODS AND RESULTS: A beta-glucosidase/xylosidase gene RuBGX1 was cloned from yak (Bos grunniens) rumen using the metagenomic technology. Recombinant RuBGX1, expressed in Escherichia coli, demonstrated high hydrolytic activities on both p-nitrophenyl-beta-d-glucopyranoside (pNP-Glc) and p-nitrophenyl-beta-d-xylopyranoside (pNP-Xyl) substrates. Analysis of the kinetic properties indicated that RuBGX1 had a lower affinity for pNP-Glc substrate as the K(m) was 0.164 mmol l(-1) for pNP-Glc and 0.03 mmol l(-1) for pNP-Xyl at pH 6.0 and 50 degrees C, respectively. The capabilities of RuBGX1 beta-xylosidase for hydrolysis of xylooligosaccharide substrates were further investigated using an endoxylanase-coupled assay. Hydrolysis time courses illustrated that a significant increase (about 50%) in the reducing sugars, including xylobiose, xylotriose and xylotetraose, was achieved by supplementing endoxylanase with RuBGX1. Enzymatic product analysis using high-performance anion-exchange chromatography-pulsed amperometric detection showed that RuBGX1 could release xyloses from intermediate xylooligosaccharides produced by endoxylanase. CONCLUSIONS: The RuBGX1 shows beta-glucosidase activity in hydrolysis of cello oligosaccharides; meanwhile, it has beta-xylosidase activity and functions synergistically with endoxylanase to promote the degradation of hemicellulosic xylans. SIGNIFICANCE AND IMPACT OF THE STUDY: This was the first to report the beta-xylosidase activity of family 3 beta-glucosidase/xylosidase functioned in the degradation of hemicellulosic xylans. The bifunctional beta glucosidase/xylosidase property of RuBGX1 can be used in simultaneous saccharification of cellulose and xylan into fermentable glucose and xylose. PMID- 22085268 TI - Genetic polymorphisms of UGT1A7 and cancer risk: evidence from 21 case-control studies. AB - The aim of our meta-analysis was to assess the association between UGT1A7 polymorphisms and cancer risk. Case?control studies containing available polymorphic alleles (UGT1A7*1,*2,*3, and*4) and genotypes categorized according to enzymatic activity (High, Intermediate, and Low) were chosen to assess this association. Twenty-one case?control studies were identified. Meta-analysis indicated that UGT1A7 had a significant effect on cancer risk. In subgroup analysis, a significantly increased risk was associated with East Asians, hepatocellular cancer, and colorectal cancer. This meta-analysis suggested that there is a cancer risk associated with UGT1A7*3, Intermediate, and Low activity UGT1A7 genotypes, which is most evident in Asian individuals. PMID- 22085269 TI - Systematic review: generating evidence-based guidelines on the concurrent use of dietary antioxidants and chemotherapy or radiotherapy. AB - The risk-benefit ratio for concurrent use of dietary antioxidants with chemotherapy or radiation therapy is a controversial topic. In this review, the medical literature on concurrent antioxidant use with chemotherapy or radiotherapy was assessed and further steps for generating evidence-based guidelines are suggested. The clinical cancer research community should cooperate and focus new studies on the use of a specific combination of antioxidant and chemotherapy or radiotherapy, and determine optimal doses for a specific cancer setting. Mechanistic studies on the interaction between antioxidants and conventional cancer therapy could lead to novel biomarkers for assessing dose adequacy. PMID- 22085270 TI - An analog of withaferin A activates the MAPK and glutathione "stress" pathways and inhibits pancreatic cancer cell proliferation. AB - Withaferin A (WA) (1) and two analogs [4-epi-withaferin A (2) and 4,27-diacetyl-4 epi-withaferin A (3)] were evaluated for antitumor activity in pancreatic cancer cells. IC(50) for 1, 2, and 3 were 0.87, 0.45, and 0.29 ?M (BxPC-3); 1.28, 1.53, and 0.52 ?M (MIAPaCa-2); and 0.59, 2.25, and 0.56 ?M (PANC-1), respectively. We chose WA analog 3 for functional studies with confirmatory RT-PCR and Western blotting. ANOVA identified 33 (MIAPaCa-2), 54 (PANC-1), and 48 (BxPC-3) gene expression changes. Fisher exact test demonstrated MAPK and glutathione pathways to be overexpressed with WA analog 3. WA analog 3 elicits a dose- and time dependent apoptosis, activates MAPK and glutathione ?stress? pathways, and inhibits proliferation. PMID- 22085271 TI - Tumor endothelial marker 8 overexpression in breast cancer cells enhances tumor growth and metastasis. AB - Tumor vasculature is known to express high levels of the longest splice variant of tumor endothelial marker 8 (TEM8). Little is known about its expression by tumor cells. Five of eight cell breast cancer cell lines tested expressed significant levels of the longest TEM8 splice variant (TEM8.1), and to a lesser extent, the shortest splice variant (TEM8.3). Breast cancer cell lines expressing high levels of TEM8 are known to be more invasive and typify a more aggressive basal-like phenotype. In vivo studies in the 4T1 murine model showed enhanced tumor growth associated with increased tumor vascularity and metastasis to lymph nodes and lungs. These data suggest that TEM8.1 expression in breast cancer cells confers a more aggressive, proangiogenic phenotype. PMID- 22085273 TI - Carnitine administration reduces cytokine levels, improves food intake, and ameliorates body composition in tumor-bearing rats. AB - Increased cytokine expression contributes to the pathogenesis of cancer anorexia?cachexia syndrome. Carnitine may reduce inflammation in chronic diseases. We tested the effects of L-propionylcarnitine (PC group) or saline (C group) on food intake (FI), body composition, and inflammatory status of MCA sarcoma-bearing rats. On tumor appearance, rats were randomly assigned to daily i.p. injection of L-propionylcarnitine (250 mg/kgBW/d; n = 8) or saline (equal volume; n = 8). FI and fat-free mass wasting improved in PC rats only (p < .01 vs. controls). Cytokines? levels decreased in PC rats vs. controls (p < .02). Results suggest that carnitine may ameliorate cancer anorexia?cachexia, via reduction of the inflammatory status. PMID- 22085272 TI - The effect of adenovirus-mediated gene expression of FHIT in small cell lung cancer cells. AB - The candidate tumor suppressor fragile histidine traid (FHIT) is frequently inactivated in small cell lung cancer (SCLC). Mutations in the p53 gene also occur in the majority of SCLC leading to the accumulation of the mutant protein. Here we evaluated the effect of FHIT gene therapy alone or in combination with the mutant p53-reactivating molecule, PRIMA-1(Met)/APR-246, in SCLC. Overexpression of FHIT by recombinant adenoviral vector (Ad-FHIT)-mediated gene transfer in SCLC cells inhibited their growth by inducing apoptosis and when combined with PRIMA-1(Met)/APR-246, a synergistic cell growth inhibition was achieved. PMID- 22085274 TI - Suppression of epidermal growth factor receptor (EGFR) expression by small hairpin RNA inhibits the growth of human nonsmall cell lung cancers bearing wild type and mutant EGFR. AB - In the present study, we have used plasmid-based RNA interference (RNAi) strategy to downregulate the expression of epidermal growth factor receptor (EGFR) in EGFR wild-type (H292) and mutant (H1975) lung tumor models. The targeted knockdown of EGFR by small hairpin RNA not only inhibited growth of H292 xenograft but also inhibited H1975 lung cancer cell and xenograft, which bore L858R/T790M EGFR and was resistant to EGFR tyrosine kinase inhibitors. These data demonstrated that small hairpin RNA was an effective therapy against mutant EGFR-expressing cancer cells and thus considered to be a promising strategy in the treatment of lung cancers. PMID- 22085275 TI - Deslongchamps annulations with benzoquinone monoketals. AB - The so-called Deslongchamps annulation of deprotonated gamma,delta-unsaturated beta-ketoesters 15 to 2-(alkoxycarbonyl)cyclohex-2-en-1-ones or similarly activated cyclohex-2-en-1-ones offers a versatile access to various kinds of decalindiones. The scope of Deslongchamps annulations was extended by establishing acceptor-substituted benzoquinone monoketals such as 13 as viable substrates. They gave octalindiones such as 35 with diastereoselectivities >= 95:5. PMID- 22085276 TI - Anticancer activity of Berberis aristata in Ehrlich ascites carcinoma-bearing mice: a preliminary study. AB - CONTEXT: Berberis aristata DC (Berberidaceae) is an important medicinal plant with claims of widespread medicinal value in indigenous medicine. It is used by herbal healers to treat oral cancers. OBJECTIVE: To evaluate the antineoplastic activity of the extracts of Berberis aristata in Ehrlich ascites carcinoma (EAC) bearing mice with cisplatin as positive control in the advanced stage of tumorigenesis. MATERIALS AND METHODS: Brine shrimp lethality bioassay (BSL) of extracts and effect on the tumor cell viability in vitro were carried out. EAC was induced in Swiss albino mice by injecting 10(6) cell/mL of tumor cell suspension i.p. Antineoplastic activity of the aqueous and ethanol extracts (100 and 6.5 mg/kg i.p., respectively) was compared with that of cisplatin (3.5 mg/kg i.p.) on the parameters such as percentage increase in weight, median survival time, and hematology. RESULTS: Ethanol extract attenuated percentage increase in weight gain (-6.86 +/- 1.50) due to tumor cell proliferation and increased the survival time (19.5 days) when compared to control group (19.10 +/- 2.31 and 16 days, respectively). However, the effect was less than that of cisplatin. In vitro cytotoxicity assay as well as BSL test showed the cytotoxic effect of the extracts. Cisplatin and the extracts reversed the tumor-induced alterations in total white blood cell count, differential leukocyte counts, total red blood cell count, and hemoglobin contents. DISCUSSION AND CONCLUSION: Of the two extracts, the ethanol extract was observed to be more efficient and the presence of alkaloids and flavonoids may be responsible for the observed anticancer effects. PMID- 22085277 TI - Screening and identification of potential active components in crude Fructus Corni using solid-phase extraction and LC-LTQ-linear ion trap mass spectrometry. AB - CONTEXT: Fructus Corni is derived from the dry ripe sarcocarp of Cornus officinalis Sieb. et Zucc. (Cornaceae). It has attracted increasingly much attention as one of the most popular and valuable herbal medicine in clinic. This paper applied a rapid and validated method to the intrinsic quality control of Fructus Corni. MATERIALS AND METHODS: The components of crude Fructus Corni were investigated by means of solid-phase extraction (SPE) and LTQ-linear ion trap mass spectrometry (MS) technique in the negative ion mode. RESULTS: The 29 detected compounds were identified by comparing the retention time and mass spectrometry data and retrieving the reference literatures. DISCUSSION AND CONCLUSION: It was concluded that a rapid and validated method was successfully applied based on SPE-LC-DAD-LTQ-linear-MS(n) which showed high sensitivity and resolution that was more suitable for identifying main components in Traditional Chinese medicines (TCMs) and their prescriptions, which would be helpful to their quality control. PMID- 22085278 TI - Effects of dietary fruits, vegetables and a herbal tea on the in vitro transport of cimetidine: comparing the Caco-2 model with porcine jejunum tissue. AB - CONTEXT: Dietary botanicals are often consumed together with allopathic medicines, which may give rise to pharmacokinetic interactions. In vitro intestinal models are useful to identify botanical-drug interactions, but they may exhibit different expressions of transporters or enzymes. OBJECTIVE: To compare the effects of selected dietary botanical extracts on cimetidine transport across two in vitro intestinal models. MATERIALS AND METHODS: Bi directional transport of cimetidine was measured across Caco-2 cell monolayers and excised porcine jejunum tissue in the absence (control) as well as the presence of verapamil (positive control) and selected plant extracts. RESULTS: Sclerocarya birrea Hochst. (Anacardiaceae) (marula) and Psidium guajava L. (Myrtaceae) (guava) crude extracts significantly decreased cimetidine efflux in both in vitro models resulting in increased absorptive transport of the drug. On the other hand, Dovyalis caffra Sim. (Flacourtiaceae) (Kei-apple), Prunus persica (L.) Batsch (Rosaceae) (peach), Aspalathus linearis (Burm. f.) R. Dahlgren (Fabaceae) (rooibos tea), Daucus carota L. (Apiaceae) (carrot), Prunus domestica A. Sav. (Rosaceae) (plum), Beta vulgaris L. (Chenopodiaceae) (beetroot) and Fragaria x ananassa (Weston) Duchesne ex Rozier. (Rosaceae) (strawberry) crude extracts exhibited different effects on cimetidine transport between the two models. DISCUSSION: Caco-2 cells were more sensitive to changes in cimetidine transport by the plant extracts and therefore may overestimate the effects of co administered plant extracts on drug transport compared to the excised pig tissue model, which is congruent with findings from previous studies. CONCLUSIONS: The excised porcine jejunum model seemed to provide a more realistic estimation of botanical-drug pharmacokinetic interactions than the Caco-2 cell model. PMID- 22085279 TI - Evaluation of cardiomyocyte hypoxia injury models for the pharmacological study in vitro. AB - CONTEXT: Traditional Herbal Medicine (THM) has many advantages that make it a promising choice for the treatment of ischemic heart disease (IHD). To study the mechanism of IHDs or pharmacological actions of THM, many hypoxia-induced cardiomyocyte injury models have been established. Radix Salvia miltorrhiza (Danshen) was used as a representative of THM. Danshen is a famous medicinal herb widely applied in Asia to relieve ischemic cardiovascular diseases. OBJECTIVE: To investigate the effects of various hypoxic conditions and discuss a suitable hypoxia model, cell viability, apoptosis, release of myocardial injury markers, and mRNA levels of target genes were tested for the first time. MATERIALS AND METHODS: Radix Salvia miltorrhiza (Danshen) was purchased from a GMP-compliant producer and both its preparation method and quality control were standardized. Cellular status, such as cell viability, apoptosis, releases of myocardial injury markers, and the mRNA level of target gene were tested by 3-[4,5-dimethylthiazol 2-yl]-2,5-diphenyltetrazolium bromide (MTT) method, biochemical analyzer, flow cytometry, Hoechst 33258 staining, and real-time PCR, respectively. RESULTS: Based on our data, we found a treppe response of cardiomyocyte in the hypoxic condition and suggested that 8 h in 2% O2 might be a suitable condition for in vitro pharmacological study of cardiomyocytes. DISCUSSION AND CONCLUSIONS: Our findings outlined more extended and in-depth capability of cardiomyocyte suffering from hypoxia, and might be of particular interest due to the high prevalence of THM pharmacological study. PMID- 22085281 TI - Molecular cytopathology and flow cytometry: pre-analytical procedures matter. PMID- 22085283 TI - Dexamethasone facilitates lipid accumulation in chicken skeletal muscle. AB - The effects of glucocorticoid on lipid metabolism of broiler chicken (Gallus gallus domesticus) skeletal muscle were investigated. Male Arbor Acres chickens (35 days old) were subjected to dexamethasone treatment for 3 days. We found that dexamethasone retards body growth while facilitating lipid accumulation. In M. pectoralis major (PM), dexamethasone increased the expression of glucocorticoid receptor (GR), fatty acid transport protein 1 (FATP1), heart fatty acid-binding protein (H-FABP) and long-chain acyl-CoA dehydrogenase (LCAD) mRNA and decreased the expression of liver carnitine palmitoyltransferase 1 (L-CPT1), adenosine monophosphate-activated protein kinase (AMPK) alpha2 and lipoprotein lipase (LPL) mRNA. LPL activity was also decreased. In M. biceps femoris (BF), the levels of GR, FATP1 and L-CPT1 mRNA were increased. AMPKalpha (Thr172) phosphorylation and CTP1 activity of skeletal muscle were decreased by dexamethasone. In fed chickens, dexamethasone enhanced very low-density lipoprotein receptor (VLDLR) expression and AMPK activity in muscle, but it impaired the expression of LPL and L-CPT1 mRNA and LPL activity in PM and augmented the expression of GR, LPL, H FABP, L-CPT1, LCAD and AMPKalpha2 mRNA in BF. Adipose triglyceride lipase (ATGL) protein expression was not affected by dexamethasone. In conclusion, in the fasting state, dexamethasone-induced-retarded fatty acid utilisation may be involved in the augmented intramyocellular lipid accumulation in both glycolytic (PM) and oxidative (BF) muscle tissues. In the fed state, dexamethasone promoted the transcriptional activity of genes related to lipid uptake and oxidation in muscles. Unmatched lipid uptake and utilisation are suggested to be involved in the augmented intramyocellular lipid accumulation. PMID- 22085282 TI - Hybrid peptide dendrimers for imaging of chemokine receptor 4 (CXCR4) expression. AB - The chemokine receptor 4 (CXCR4), which is overexpressed in many types of cancer, is an emerging target in the field of molecular imaging and therapeutics. The CXCR4 binding of several peptides, including the cyclic Ac-TZ14011, has already been validated. In this study mono-, di- and tetrameric Ac-TZ14011-containing dendrimers were prepared and functionalized with a multimodal (hybrid) label, consisting of a Cy5.5-like fluorophore and a DTPA chelate. Confocal microscopy revealed that all three dendrimers were membrane bound at 4 degrees C, consistent with CXCR4 binding in vitro. The unlabeled dimer and tetramer had a somewhat lower affinity for CXCR4 than the unlabeled monomer. However, when labeled with the multimodal label the CXCR4 affinity of the dimer and tetramer was considerably higher compared to that of the labeled monomer. On top of that, biodistribution studies revealed that the additional peptides in the dimer and tetramer reduced nonspecific muscle uptake. Thus, multimerization of the cyclic Ac-TZ14011 peptide reduces the negative influence of the multimodal label on the receptor affinity and the biodistribution. PMID- 22085284 TI - Population-based study of erectile dysfunction and polypharmacy. AB - Study Type - Symptom prevalence (population cohort). Level of Evidence 1b. What's known on the subject? and What does the study add? It is known that medical conditions such as diabetes, high blood pressure, high cholesterol, smoking and prescribed medications cause erectile dysfunction (ED). This has been studied at the molecular level and reported in population studies. The present study shows that, after accounting for known medical problems, there is a dose-response relationship, in which worsening degrees of ED are seen when a greater number of medications are taken, regardless if they are prescribed or over the counter. The study can help primary care doctors and urologists to make a differential diagnosis of ED and it can also help improve patient's erectile function by tailoring and curtailing current medication use to maximize therapeutic benefit but minimize ED side effects in men, thus improving health-related quality of life. OBJECTIVE: * To study the association between erectile dysfunction (ED) and polypharmacy use in a large, ethnically and racially diverse cohort of men enrolled in the California Men's Health Study (CMHS). PATIENTS AND METHODS: * Men from the Kaiser Permanente Southern California (KPSC) health plan, enrolled in the CMHS in 2002, had an age range of 45-69 years. ED and comorbidities of these subjects were identified by questionnaire responses. * The number of drugs taken was determined from the year before enrollment through electronic pharmacy records and questionnaire responses. RESULTS: * Among the 37 712 (KPSC) subjects, 10 717 (29%) reported moderate or severe ED. * Across all age groups, ED was more prevalent as the number of medications increased. * In men taking 0-2, 3-5,6-9 and >= 10 medications, the percentage of men reporting moderate ED was 15.9, 19.7, 25.5 and 30.9%, respectively (P < 0.001). * With adjustment for age, race, smoking, diabetes, hypertension, hyperlipidaemia, peripheral vascular disease, coronary artery disease and body mass index, men taking >10 drugs were more likely to have ED (odds ratio = 2.32, 95% confidence interval 2.14-2.52) with evidence of a dose-response relationship. CONCLUSION: * These data suggest that the number of medications a man takes is associated with worse ED, even after comorbidities have been taken into account. PMID- 22085286 TI - Condom use within marriage: an assessment of changes in South Africa and Uganda. AB - The aim of the study is to measure trends in condom use in marital and cohabiting relationships in South Africa and Uganda. The data for the study come from two cross sectional surveys conducted in 1998 and 2008 among adult men and women and their partners in KwaZulu-Natal, South Africa and the Jinja district, Uganda. The findings suggest that consistent condom use has risen substantially in both countries. The percentage reporting consistent condom use in the South African sample of husbands increased from 2.5% in 1998 to 12% in 2008 and from 5.5 to 12.5% among wives. In Uganda, the corresponding trends are 1.1-8.3% for husbands and 4-8.6% for wives. In both countries, condom use was considerably higher among the minority of couples where one or both partners were thought to be HIV positive. Increasingly, in both countries condoms are also used for contraceptive purposes. Condoms play a role in preventing HIV infection but the challenge is for prevention programs to broaden their focus toward meeting the needs of married and cohabiting couples. PMID- 22085287 TI - Molecular phylogeny of diploid Hordeum species and incongruence between chloroplast and nuclear datasets. AB - The phylogeny of diploid Hordeum species has been studied using both chloroplast and nuclear gene sequences. However, the studies of different nuclear datasets of Hordeum species often arrived at similar conclusions, whereas the studies of different chloroplast DNA data generally resulted in inconsistent conclusions. Although the monophyly of the genus is well supported by both morphological and molecular data, the intrageneric phylogeny is still a matter of controversy. To better understand the evolutionary history of Hordeum species, two chloroplast gene loci (trnD-trnT intergenic spacer and rps16 gene) and one nuclear marker (thioreoxin-like gene (HTL)) were used to explore the phylogeny of Hordeum species. Two obviously different types of trnD-trnT sequences were observed, with an approximately 210 base pair difference between these two types: one for American species, another for Eurasian species. The trnD-trnT data generally separated the diploid Hordeum species into Eurasian and American clades, with the exception of Hordeum marinum subsp. gussoneanum. The rps16 data also grouped most American species together and suggested that Hordeum flexuosum has a different plastid type from the remaining American species. The nuclear gene HTL data clearly divided Hordeum species into two clades: the Xu+H genome clade and the Xa+I genome clade. Within clades, H genome species were well separated from the Xu species, and the I genome species were well separated from the Xa genome species. The incongruence between chloroplast and nuclear datasets was found and discussed. PMID- 22085288 TI - Case mix in paediatric rheumatology: implications for training in Australia. AB - BACKGROUND: Despite a move towards the provision of specialist training in Australia in settings that extend beyond the public hospital system, formal comparisons of case mix between public and private specialty clinics have rarely been performed. It is therefore unclear for many specialties how well training in one setting prepares trainees for practice in the other. AIMS: This study aims to compare the case mix of paediatric rheumatology patients seen in public and private settings and the referral sources of patients in each. METHODS: An audit of all new patients seen in the public and private paediatric rheumatology clinics on campus at Royal Children's Hospital between June 2009 and January 2011. Data related to demographics, primary diagnosis, referral source and location seen were abstracted and compared. RESULTS: Eight hundred and seventy six new patients were seen during the period of interest. Of these, 429 patients (48.9%) were seen in private clinics. The commonest diagnostic categories for both type of clinics were non-inflammatory musculoskeletal pain/orthopaedic conditions (public 39.4%, private 33.6%) followed by juvenile idiopathic arthritis (public 16.6%, %, private 18.6%), other skin/soft tissue disorders (public 8.7%, private 9.6%) and pain syndromes (public 4.9%, private 11.4%). Patients with haematological and vasculitic disorders were predominantly seen in public clinics. The commonest source of referrals to both clinics was general practitioners (public 40.6%, private 53.1%). CONCLUSION: The case mix in private paediatric rheumatology clinics closely mirrors that of public clinics at our centre. Training in either setting would provide sufficient case-mix exposure to prepare trainees for practice in the other. PMID- 22085290 TI - Characterization of supported lipid bilayer disruption by chrysophsin-3 using QCM D. AB - Antimicrobial peptides (AMPs) are naturally occurring polymers that can kill bacteria by destabilizing their membranes. A quartz crystal microbalance with dissipation monitoring (QCM-D) was used to better understand the action of the AMP chrysophsin-3 on supported lipid bilayers (SLB) of phosphatidylcholine. Interaction of the SLB with chrysophsin-3 at 0.05 MUM demonstrated changes in frequency (Deltaf) and energy dissipation (DeltaD) that were near zero, indicating little change in the membrane. At higher concentrations of chyrsophsin 3 (0.25-4 MUM), decreases in Deltaf of up to 7 Hz were measured. These negative frequency changes suggest that mass was being added to the SLB, possibly due to peptide insertion into the membrane. At a chrysophsin-3 concentration of 10 MUM, there was a net mass loss, which was attributed to pore formation in the membrane. QCM-D can be used to describe a mechanistic relationship between AMP concentration and interaction with a model cell membrane. PMID- 22085289 TI - Reconstitution of KCNE1 into lipid bilayers: comparing the structural, dynamic, and activity differences in micelle and vesicle environments. AB - KCNE1 (minK), found in the human heart and cochlea, is a transmembrane protein that modulates the voltage-gated potassium KCNQ1 channel. While KCNE1 has previously been the subject of extensive structural studies in lyso-phospholipid detergent micelles, key observations have yet to be confirmed and refined in lipid bilayers. In this study, a reliable method for reconstituting KCNE1 into lipid bilayer vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho(1'-rac glycerol) (sodium salt) (POPG) was developed. Microinjection of the proteoliposomes into Xenopus oocytes expressing the human KCNQ1 (K(V)7.1) voltage gated potassium channel led to nativelike modulation of the channel. Circular dichroism spectroscopy demonstrated that the percent helicity of KCNE1 is significantly higher for the protein reconstituted in lipid vesicles than for the previously described structure in 1.0% 1-myristoyl-2-hydroxy-sn-glycero-3 phospho(1'-rac-glycerol) (sodium salt) (LMPG) micelles. SDSL electron paramagnetic resonance spectroscopic techniques were used to probe the local structure and environment of Ser28, Phe54, Phe57, Leu59, and Ser64 of KCNE1 in both POPC/POPG vesicles and LMPG micelles. Spin-labeled KCNE1 cysteine mutants at Phe54, Phe57, Leu59, and Ser64 were found to be located inside POPC/POPG vesicles, whereas Ser28 was found to be located outside the membrane. Ser64 was shown to be water inaccessible in vesicles but found to be water accessible in LMPG micelle solutions. These results suggest that key components of the micelle derived structure of KCNE1 extend to the structure of this protein in lipid bilayers but also demonstrate the need to refine this structure using data derived from the bilayer-reconstituted protein to more accurately define its native structure. This work establishes the basis for such future studies. PMID- 22085291 TI - The 20-kDa chaperone-like protein of Bacillus thuringiensis ssp. israelensis enhances yield, crystal size and solubility of Cry3A. AB - AIMS: To determine whether the 20-kDa chaperone-like protein of Bacillus thuringiensis ssp. israelensis enhances synthesis, crystallization and solubility of the Cry3A coleopteran toxin and whether the crystalline inclusions produced are toxic to neonates of the Colorado potato beetle, Leptinotarsa decemlineata. METHODS AND RESULTS: The cry3A gene was expressed in the 4Q7 strain of B. thuringiensis ssp. israelensis in the absence or presence of the 20-kDa gene. The 20-kDa protein enhanced Cry3A yield by 2.7-fold per unit of fermentation medium. Crystal volumes averaged 2.123 and 0.964 MUm(3) when synthesized in, respectively, the presence or absence of the 20-kDa protein. Both crystals were soluble at pH 5 and pH 6; however, the larger crystal was 1.7* and 1.5* more soluble at, respectively, pH 7 and pH 10. No significant difference in toxicity against L. decemlineata neonates was observed. CONCLUSIONS: This report demonstrated that the 20-kDa chaperone-like protein enhances yield, volume and solubility of the coleopteran Cry3A crystalline inclusions per unit crystal/spore mixture. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report showing that an accessory protein (20-kDa) could enhance synthesis and crystallization of Cry3A, a finding that could be beneficial for commercial production of this coleopteran-specific insecticidal protein for microbial insecticides and possibly even for transgenic crops. PMID- 22085292 TI - Hybrid aminoglycoside antibiotics via Tsuji palladium-catalyzed allylic deoxygenation. AB - Biosynthetically inspired manipulation of the antibiotic paromomycin led, in six high-yielding steps, to a ring A harboring an alpha,beta-unsaturated 6'-aldehyde and an allylic 3'-methylcarbonate group. Tsuji deoxygenation in the presence of 5 mol % Pd(2)(dba)(3) and Bu(3)P granted access to a novel series of 3',4'-dideoxy 4',5'-dehydro ring A hybrids. The neomycin-sisomicin hybrid exhibited superior in vitro antibacterial activity to the parent compound neomycin. PMID- 22085293 TI - Bonding in ammonia borane: an analysis based on the natural orbitals for chemical valence and the extended transition state method (ETS-NOCV). AB - In the present study the natural orbitals for chemical valence (NOCVs) combined with the energy decomposition scheme (ETS) were used to characterize bonding in various clusters of ammonia borane (borazane): dimer D, trimer TR, tetramer TE, and the crystal based models: nonamer N and tetrakaidecamer TD. ETS-NOCV results have shown that shortening of the B-N bond (by ~0.1 A) in ammonia borane crystal (as compared to isolated borazane molecule) is related to the enhancement of donation (by 6.5 kcal/mol) and electrostatic (by 11.3 kcal/mol) contributions. This, in turn, is caused solely by the electrostatic dipole-dipole interaction between ammonia borane units; dihydrogen bonding, BH...HN, formed between borazane units exhibits no direct impact on B-N bond contraction. On the other hand, formation of dihydrogen bonding appeared to be very important in the total stabilization of single borazane unit, namely, ETS-based data indicated that it leads to significant electronic stabilization DeltaE(orb) = -17.5 kcal/mol, which is only slightly less important than the electrostatic term, DeltaE(elstat) = 19.4 kcal/mol. Thus, both factors contribute to relatively high melting point of the borazane crystal. Deformation density contributions (Deltarho(i)) obtained from NOCVs allowed to conclude that dihydrogen bonding is primarily based on outflow of electron density from B-H bonding orbitals to the empty sigma*(N-H) (charge transfer component). Equally important is the covalent contribution resulting from the shift of the electron density from hydrogen atoms of both NH and BH groups to the interatomic regions of NH...HB. Quantitatively, averaged electronic strength of dihydrogen bond per one BH...HN link varies from 1.95 kcal/mol (for the crystal structure model, N), 2.47 kcal/mol (for trimer TR), through 2.65 kcal/mol (for tetramer TE), up to 3.95 kcal/mol (for dimer D). PMID- 22085294 TI - 120-W 2-um thulium:yttrium-aluminium-garnet vapoenucleation of the prostate: 12 month follow-up. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Thulium VapoEnucleation of the prostate (ThuVEP) has been introduced as a minimally invasive treatment modality of benign prostate obstruction (BPO). This study reports the largest series of patients with symptomatic BPO undergoing ThuVEP. Efficacy of this procedure was confirmed by prostate volume and PSA measurements at 12-month follow up, which have not been reported after ThuVEP so far. OBJECTIVE: To evaluate the safety and efficacy of 120-W 2-um thulium:yttrium-aluminium-garnet (YAG) vapoenucleation of the prostate (ThuVEP) for patients with symptomatic benign prostatic obstruction. METHOD: In total, 207 consecutive patients undergoing ThuVEP at our institution were evaluated prospectively. ThuVEP was carried out using the 120-W 2-um continuous-wave Tm:YAG laser. The enucleated tissue was then morcellated within the bladder. Patient demographic, perioperative and 12-month follow-up data were analysed. The complications were assessed. RESULTS: Mean preoperative prostate volume was 57.8 +/- 31.5 mL. Total operation duration averaged 64.9 +/- 29.9 min, and the enucleation time was 36.5 +/- 20.1 min. The mean catheter time was 2.2 +/ 0.6 days. Thirteen (6.28%) patients required a second-look operation in the immediate postoperative course (failed morcellation n= 1, clot retention n= 4, residual tissue at the apex of the prostate n= 8). Four patients needed blood transfusions (1.93%) postoperatively. In all, 147 (71%) patients were available for review at the 12-month follow-up mark. Quality of life (4.4 +/- 1.3 vs 1.2 +/ 1.1), international prostate symptom score (21.9 +/- 7.2 vs 5.1 +/- 4), maximum urinary flow rate (9.4 +/- 3.8 vs 23.5 +/- 10.9 mL/s), postvoiding residual urine (159.2 +/- 153.2 vs 26.7 +/- 38.3 mL), prostate-specific antigen (5.0 +/- 5.2 vs 0.6 +/- 0.5 ng/mL) and prostate volume (57.8 +/- 31.5 vs 10.7 +/- 4.4 mL) changed significantly (P= 0.000). Median prostate-specific antigen reduction and prostate volume reduction were 87% and 80% respectively at follow-up. Urethral stricture and bladder neck contracture developed in 1.45% and 1.93% respectively of the patients. CONCLUSION: 120-W ThuVEP is a safe and efficacious procedure for the treatment of symptomatic benign prostatic obstruction. The incidence of complications with ThuVEP was low. PMID- 22085295 TI - Early maternal separation has mild effects on cardiac autonomic balance and heart structure in adult male rats. AB - Early life adverse experiences have long-term physiologic and behavioral effects and enhance stress sensitivity. This study examined the effects of maternal separation (MS) on cardiac stress responsivity and structure in adulthood. Male Wistar rats were separated from the dams for 3 h per day from postnatal days 2 through 15. When exposed to 5-day intermittent restraint stress (IRS) as adults, MS, and control rats showed similar acute modifications of cardiac sympathovagal balance, quantified via heart rate variability analysis. In addition, MS had no effect on cardiac pacemaker intrinsic activity (as revealed by autonomic blockade with scopolamine and atenolol) and did not affect the circadian rhythmicity of heart rate, neither before nor after IRS. However, MS differed from control rats in cardiac parasympathetic drive following IRS, which was heightened in the latter but remained unchanged in the former, both during the light and dark phases of the daily rhythm. The evaluation of adult cardiac structure indicated that stress experienced during a crucial developmental period induced only modest changes, involving cardiomyocyte hypertrophy, increased density of vascular structures, and myocardial fibrosis. The mildness of these functional-structural effects questions the validity of MS as a model for early stress-induced cardiac disease in humans. PMID- 22085296 TI - Molecular characterization of pyraclostrobin resistance and structural diversity of the cytochrome b gene in Botrytis cinerea from apple. AB - Botrytis cinerea isolates obtained from apple orchards were screened for resistance to the quinone outside inhibitor (QoI) pyraclostrobin. Of the 220 isolates tested, 43 (19.5%) were resistant to pyraclostrobin. Analysis of partial sequences of the cytochrome b gene (cyt b) in five pyraclostrobin-resistant (PR) and five pyraclostrobin-sensitive (PS) isolates showed that PR isolates harbored the point mutation leading to the substitution of glycine by alanine at codon position 143 in cyt b (G143A). Two pairs of allele-specific primers were designed based on this point mutation, and allele-specific polymerase chain reaction analysis with these primers showed that all 73 PR isolates (including 30 collected from decayed apple fruit) harbored the G143A mutation but PS isolates did not. Six pairs of primers were designed to analyze the presence of various introns in cyt b. There were six types (I to VI) of cyt b present in 247 isolates of B. cinerea collected from various apple-production areas in Washington State. Of the 247 isolates, 23 had type I cyt b containing all four introns (Bcbi-67/68, Bcbi-131/132, Bcbi-143/144, and Bcbi-164), 176 had type II cyt b containing three introns (Bcbi-67/68, Bcbi-131/132, and Bcbi-164), six had type III cyt b containing two introns (Bcbi-67/68 and Bcbi-131/132), one had type IV cyt b containing two introns (Bcbi-131/132 and Bcbi-164), one had type V cyt b containing only the Bcbi-131/132 intron, and 40 had type VI cyt b containing no introns. This is the first report of types III to VI cyt b present in B. cinerea. All 73 PR isolates did not carry the Bcbi-143/144 intron in cyt b. Of the 247 isolates tested, >90% did not carry the Bcbi-143/144 intron in cyt b, suggesting that B. cinerea populations from apple pose a high inherent risk for the development of resistance to QoIs because the presence of this intron in cyt b prevents the occurrence of G143A-mediated resistance. Analysis of genetic background based on three microsatellite primers showed that PR isolates originated from different lineages, and there was no correlation between cyt b types (I, II, and III) and the genetic background of the isolates; however, isolates carrying type VI cyt b might originate from the same lineage. PMID- 22085297 TI - Characterization of CbCyp51 from field isolates of Cercospora beticola. AB - The hemibiotrophic fungus Cercospora beticola causes leaf spot of sugar beet. Leaf spot control measures include the application of sterol demethylation inhibitor (DMI) fungicides. However, reduced sensitivity to DMIs has been reported recently in the Red River Valley sugar beet-growing region of North Dakota and Minnesota. Here, we report the cloning and molecular characterization of CbCyp51, which encodes the DMI target enzyme sterol P450 14alpha-demethylase in C. beticola. CbCyp51 is a 1,632-bp intron-free gene with obvious homology to other fungal Cyp51 genes and is present as a single copy in the C. beticola genome. Five nucleotide haplotypes were identified which encoded three amino acid sequences. Protein variant 1 composed 79% of the sequenced isolates, followed by protein variant 2 that composed 18% of the sequences and a single isolate representative of protein variant 3. Because resistance to DMIs can be related to polymorphism in promoter or coding sequences, sequence diversity was assessed by sequencing >2,440 nucleotides encompassing CbCyp51 coding and flanking regions from isolates with varying EC(50) values (effective concentration to reduce growth by 50%) to DMI fungicides. However, no mutations or haplotypes were associated with DMI resistance or sensitivity. No evidence for alternative splicing or differential methylation of CbCyp51 was found that might explain reduced sensitivity to DMIs. However, CbCyp51 was overexpressed in isolates with high EC(50) values compared with isolates with low EC(50) values. After exposure to tetraconazole, isolates with high EC(50) values responded with further induction of CbCyp51, with a positive correlation of CbCyp51 expression and tetraconazole concentration up to 2.5 MUg ml(-1). PMID- 22085299 TI - Larval Bradysia impatiens (Diptera: Sciaridae) potential for vectoring Pythium root rot pathogens. AB - A series of laboratory experiments were conducted to investigate the capacity of Bradysia impatiens (Johannsen) larvae to ingest propagules from two strains each of Pythium aphanidermatum (Edson) Fitzp. and P. ultimum Trow and transmit the pathogens to healthy geranium seedlings on a filter-paper substrate in petri dishes. The capacity of fungus gnat larvae to transmit P. aphanidermatum to seedlings rooted in a commercial peat-based potting mix and germination of Pythium oospores and hyphal swellings before and after passage through the guts of larval fungus gnats were also examined. Assays revealed that Pythium spp. transmission by larval fungus gnats varied greatly with the assay substrate and also with the number and nature of ingested propagules. Transmission was highest (65%) in the petri dish assays testing larvae fed P. aphanidermatum K-13, a strain that produced abundant oospores. Transmission of strain K-13 was much lower (<6%) in plug cells with potting mix. Larvae were less efficient at vectoring P. ultimum strain PSN-1, which produced few oospores, and no transmission was observed with two non-oospore-producing strains: P. aphanidermatum Pa58 and P. ultimum P4. Passage of P. aphanidermatum K-13 through larval guts significantly increased oospore germination. However, decreased germination of hyphal swellings was observed following larval gut passage for strains of P. ultimum. These results expand previous studies suggesting that larval fungus gnats may vector Pythium spp. PMID- 22085298 TI - The filamentous phage phiRSS1 enhances virulence of phytopathogenic Ralstonia solanacearum on tomato. AB - Ralstonia solanacearum is the causative agent of bacterial wilt in many important crops. phiRSS1 is a filamentous phage that infects R. solanacearum strains. Upon infection, it alters the physiological state and the behavior of host cells. Here, we show that R. solanacearum infected by phiRSS1 becomes more virulent on host plants. Some virulence and pathogenicity factors, such as extracellular polysaccharide (EPS) synthesis and twitching motility, increased in the bacterial host cells infected with phiRSS1, resulting in early wilting. Tomato plants inoculated with phiRSS1-infected bacteria wilted 2 to 3 days earlier than those inoculated with wild-type bacteria. Infection with phiRSS1 induced early expression of phcA, the global virulence regulator. phcA expression was detected in phiRSS1-infected cells at cell density as low as 10(4) CFU/ml. Filamentous phages are assembled on the host cell surface and many phage particles accumulate on the cell surface. These surface-associated phage particles (phage proteins) may change the cell surface nature (hydrophobicity) to give high local cell densities. phiRSS1 infection also enhanced PilA and type IV pilin production, resulting in increased twitching motility. PMID- 22085300 TI - Phenotypic variation within a clonal lineage of Phytophthora infestans infecting both tomato and potato in Nicaragua. AB - Late blight caused by Phytophthora infestans (Mont.) de Bary is a constraint to both potato and tomato crops in Nicaragua. The hypothesis that the Nicaraguan population of P. infestans is genotypically and phenotypically diverse and potentially subdivided based on host association was tested. A collection of isolates was analyzed using genotypic markers (microsatellites and mitochondrial DNA haplotype) and phenotypic markers (mating type, virulence, and fungicide sensitivity). The genotypic analysis revealed no polymorphism in 121 of 132 isolates of P. infestans tested. Only the Ia haplotype and the A2 mating type were detected. Most of the tested isolates were resistant to metalaxyl. The virulence testing showed variation among isolates of P. infestans. No evidence was found of population differentiation among potato and tomato isolates of P. infestans based on the genotypic and phenotypic analysis. We conclude that the Nicaraguan population of P. infestans consists of a single clonal lineage (NI-1) which belongs to the A2 mating type and the Ia mitochondrial DNA haplotype. Moreover, based on the markers used, this population of P. infestans does not resemble the population in countries from which potato seed is imported to Nicaragua or the population in neighboring countries. The data presented here indicate that the NI-1 clonal lineage is the primary pathogen on both potato and tomato, and its success on both host species is unique in a South American context. PMID- 22085301 TI - BIRC6/Apollon gene expression in childhood acute leukemia: impact on therapeutic response and prognosis. AB - OBJECTIVE: Although BIRC6/Apollon seems to play a critical role as an antiapoptotic regulator, its clinical relevance in acute leukemia remains largely elusive. Therefore, we aimed to investigate BIRC6 gene expression in childhood acute leukemia in relation to clinicopathological characteristics at presentation, therapeutic response, and prognosis. METHODS: BIRC6 expression level was assessed in 75 children with acute leukemia; 30 patients with acute myeloblastic leukemia (AML) and 45 patients with acute lymphoblastic leukemia (ALL) using real-time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The median level of BIRC6 expression did not differ significantly between AML and ALL patients. BIRC6 expression level was higher in patients with AML and ALL with extramedullary involvement, white blood cell (WBC) count >= 10 * 10(9) /L, and unfavorable cytogenetics at diagnosis. BIRC6 gene expression was higher in patients with unfavorable response to therapy at day 14, those who developed relapse or died in both leukemic groups. The best cutoff value of BIRC6 to predict therapeutic response and disease outcome was determined. AML and ALL patients with BIRC6 overexpression had significantly shorter overall and disease free survivals. CONCLUSIONS: This is the first report to study BIRC6 gene in pediatric ALL. Our results suggested that BIRC6 gene expression could be considered as an adverse risk factor in childhood acute leukemia and, hence, could be used to guide therapeutic regimens. PMID- 22085302 TI - Clinical significance of IEX-1 expression in ovarian carcinoma. AB - BACKGROUND: The stress-inducible immediate early response gene X-1 (IEX-1) regulates cell proliferation and apoptosis in a cell type and stimulus-dependent manner. The aim of this study was to investigate IEX-1 expression and its role in apoptosis of ovarian epithelial tumors for potential use in clinical diagnosis and therapy. METHODS: IEX-1 expression was examined in paraffin-embedded specimens from 77 patients with epithelial ovarian tumors using immunohistochemistry. Correlation between IEX-1 expression and other clinicopathological parameters was evaluated. Apoptosis of tumor cells was detected by terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: IEX-1 expression was significantly lower in ovarian cancers compared to cystadenomas and borderline tumors (p < .05). The expression was significantly associated with FIGO stage and histological grade (p < .05), but not with age, histological type, or residual tumor (p > .05). A positive correlation was also observed between IEX-1 expression and apoptotic index (p < .01) or survival (p=.005). CONCLUSION: With the development of epithelial ovarian tumors from benign to malignant, IEX-1 expression is decreased, concomitant with a decreased rate of cell apoptosis. Thus, IEX-1 is pro-apoptotic in the development of epithelial ovarian cancer. The pro-apoptotic activity may take part in restraining tumor growth at the early stage of ovarian epithelial cancer, whereas its decreased expression probably contributes to the abnormal survival advantage for malignant cancer. Altered IEX-1 expression can potentially be a new predictor of the malignant transformation and a prognostic indicator for cancer therapy. PMID- 22085303 TI - Metachromatic leukodystrophy and its effects on the gallbladder: a case report. AB - Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of arylsulfatase A enzyme. This deficiency leads to accumulation of sulfatides in the central nervous system and other organs, such as the gallbladder. Here the authors discuss a 9-year-old Middle Eastern patient with late-infantile-type MLD who presented with symptoms of cholecystitis. Radiographic studies revealed an enlarged gallbladder with a thickened wall and a pericholecystic fluid collection with peripheral calcifications. Gross examination of the gallbladder showed multiple small to medium-sized papillary projections involving the entire mucosal surface. Sections through the gallbladder wall revealed multilocular dilated mucin-producing cystic spaces. Microscopically, the mucosa showed numerous papillary projections with complex folds lined by mucin-producing cuboidal to tall columnar cells. The cystic spaces were composed of numerous markedly distended Rokitansky-Aschoff sinuses filled with mucin. Ultrastructurally, the epithelial cells and macrophages showed frequent secondary lysosomes containing closely packed lamellar amorphous to prismatic material with alternating leaflets and tubules, imparting a "herringbone" or "tuffstone" pattern. This case illustrates the features of gallbladder involvement in MLD and the potential role of ultrastructural examination in diagnosis of MLD. PMID- 22085304 TI - Mechanism of visceral fat reduction in Tsumura Suzuki obese, diabetes (TSOD) mice orally administered beta-cryptoxanthin from Satsuma mandarin oranges (Citrus unshiu Marc). AB - The carotenoid beta-cryptoxanthin (beta-CRX) is abundant in Satsuma mandarins (Citrus unshiu Marc). Several studies have shown a relationship between Satsuma mandarin consumption and a low risk of several diseases, for example, diabetes, gout, and hypertension, suggesting beta-CRX involvement in disease prevention. We investigated the effect of beta-CRX on mildly obese males. beta-CRX administration reduced visceral adipose tissue, body weight, and abdominal circumference. However, the detailed mechanism by which beta-CRX mediates these changes remains unknown. To identify this mechanism, we used an obese model mouse (TSOD). Oral beta-CRX administration repressed body weight, abdominal adipose tissue weight, and serum lipid concentrations in TSOD; these results are identical to previous human trial results. beta-CRX administration significantly repressed adipocyte hypertrophy. Gene expression analysis strongly indicated that beta-CRX can alter cytokine secretion and cell proliferation. These results suggest that beta-CRX derived from Satsuma mandarins can help prevent obesity by repressing hypertrophy of abdominal adipocytes. PMID- 22085305 TI - Determination of antioxidant activity of extracts and fractions obtained from Galinsoga parviflora and Galinsoga quadriradiata, and a qualitative study of the most active fractions using TLC and HPLC methods. AB - Taking into account the role of reactive oxygen species in the development of inflammation, and the application of the plants of genus Galinsoga Ruiz & Pav. in folk medicines for inflammatory states, we investigated and compared the antioxidant activities of particular Galinsoga extracts and fractions. The compositions of the most active fractions were studied using thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) methods. The extracts and fractions from Galinsoga parviflora Cav. and Galinsoga quadriradiata Ruiz et Pav. possess dose-dependent free radical-scavenging ability against DPPH* and superoxide radicals, as well as inhibitory effects on linoleic acid peroxidation in a manner comparable to gallic acid. In the most active fractions, flavonoids, patulitrin, quercimeritrin, quercitagetrin and caffeoyl derivatives were detected. Our research demonstrates that the investigated herbs are an interesting source of preparations with significant antioxidant effects. Our results justify the use of both raw materials in inflammatory diseases, among others, due to their ability to prevent free radical-induced deleterious effects. PMID- 22085306 TI - A qualitative study of barriers to consistent condom use among HIV-1 serodiscordant couples in Kenya. AB - This study explored barriers to consistent condom use among heterosexual HIV-1 serodiscordant couples who were aware of the HIV-1 serodiscordant status and had been informed about condom use as a risk reduction strategy. We conducted 28 in depth interviews and 9 focus group discussions among purposively selected heterosexual HIV-1 serodiscordant couples from Thika and Nairobi districts in Kenya. We analyzed the transcribed data with a grounded theory approach. The most common barriers to consistent condom use included male partners' reluctance to use condoms regardless of HIV-1 status coupled with female partners' inability to negotiate condom use, misconceptions about HIV-1 serodiscordance, and desire for children. Specific areas of focus should include development of skills for women to effectively negotiate condom use, ongoing information on HIV-1 serodiscordance and education on safer conception practices that minimize risk of HIV-1 transmission. PMID- 22085307 TI - Joint estimation of contemporary seed and pollen dispersal rates among plant populations. AB - There are few statistical methods for estimating contemporary dispersal among plant populations. A maximum-likelihood procedure is introduced here that uses pre- and post-dispersal population samples of biparentally inherited genetic markers to jointly estimate contemporary seed and pollen immigration rates from a set of discrete external sources into a target population. Monte Carlo simulations indicate that accurate estimates and reliable confidence intervals can be obtained using this method for both pollen and seed migration rates at modest sample sizes (100 parents/population and 100 offspring) when population differentiation is moderate (F(ST) >= 0.1), or by increasing pre-dispersal samples (to about 500 parents/population) when genetic divergence is weak (F(ST) = 0.01). The method exhibited low sensitivity to the number of source populations and achieved good accuracy at affordable genetic resolution (10 loci with 10 equifrequent alleles each). Unsampled source populations introduced positive biases in migration rate estimates from sampled sources, although they were minor when the proportion of immigration from the latter was comparatively low. A practical application of the method to a metapopulation of the Australian resprouter shrub Banksia attenuata revealed comparable levels of directional seed and pollen migration among dune groups, and the estimate of seed dispersal was higher than a previous estimate based on conservative assignment tests. The method should be of interest to researchers and managers assessing broad-scale nonequilibrium seed and pollen gene flow dynamics in plants. PMID- 22085309 TI - Risk factors for community-acquired pneumonia in pre-school-aged children. AB - AIM: To identify risk factors for children developing and being hospitalised with community-acquired pneumonia. METHODS: Children <5 years old residing in urban Auckland, New Zealand were enrolled from 2002 to 2004. To assess the risk of developing pneumonia, children hospitalised with pneumonia (n= 289) plus children with pneumonia discharged from the Emergency Department (n= 139) were compared with a random community sample of children without pneumonia (n= 351). To assess risk of hospitalisation, children hospitalised with pneumonia were compared with the children discharged from the Emergency Department. Adjusted odds ratio (OR) with 95% confidence intervals (CIs) were used to estimate the risk of pneumonia and hospitalisation with pneumonia. RESULTS: After adjustment for season, age and ethnicity there was an increased risk of pneumonia associated with lower weight for height (OR 1.28, 95% CI 1.10-1.51), spending less time outside (1.96, 1.11 3.47), previous chest infections (2.31, 1.55-3.43) and mould in the child's bedroom (1.93, 1.24-3.02). There was an increased risk of pneumonia hospitalisation associated with maternal history of pneumonia (4.03, 1.25-16.18), living in a more crowded household (2.87, 1.33-6.41) and one with cigarette smokers (1.99, 1.05-3.81), and mould in the child's bedroom (2.39, 1.25-4.72). CONCLUSIONS: Lower quality living environments increase the risk of pneumonia and hospitalisation with pneumonia in New Zealand. Poorer nutritional status may also increase the risk of pneumonia. Improving housing quality, decreased cigarette smoke exposure and early childhood nutrition may reduce pneumonia disease burden in New Zealand. PMID- 22085308 TI - A unique non-catenane interlocked self-assembled supramolecular architecture and its photophysical properties. AB - A novel, interlocked, self-assembled (M(2)L(2))(2) molecular architecture was constructed from an arene-Ru acceptor and a 1,4-di(pyridin-4-yl)buta-1,3-diyne donor. Two M(2)L(2) units, with cavities of ~7.21 A, spontaneously interlock, with one unit encapsulating a twin in a non-catenane fashion. The dimeric host guest complex thus formed is unique among two-dimensional self-assemblies and is stabilized by pi-pi interactions between the M(2)L(2) units. PMID- 22085310 TI - Similarities and differences within members of the Ff family of filamentous bacteriophage viruses. AB - The filamentous bacteriophage viruses of the Ff family, fd and M13, slightly differ in their genome, and their 50-residue-long major capsid proteins have a single site difference: the uncharged asparagine-12 in M13 is replaced with a negatively charged aspartate in fd. We have used magic-angle spinning solid-state NMR spectroscopy to site-specifically assign the resonances belonging to the capsid protein of M13. Assignment of several mobile residues was facilitated by using J-based spectroscopy, which in addition provided sugar-base contacts in the M13-DNA stemming from two-bond scalar couplings. A comparison between M13 and fd bacteriophages reveals that the two virions have a very conserved and stable structure, manifested in negligibly small chemical shift differences and similar dynamic properties for nearly all resonances. The principal difference between the two phages involves residues in the vicinity of residue 12. We suggest that the elimination of the single charge at position 12 throughout the entire assembly affects the electrostatic and hydrogen-bonding interaction network governing inter- and intraresidue contacts, mainly by the rearrangement of the positively charged lysine residue at position 8. PMID- 22085311 TI - Hyperactive alpha-amylase production by Aspergillus oryzae IFO 30103 in a new bioreactor. AB - AIMS: To improve the alpha-amylase production in solid-state fermentation (SSF) condition utilizing a new bioreactor (NB) system. METHODS AND RESULTS: In NB system, 20 g of wheat bran moistened with liquid medium in 1:1 ratio (w/v) was taken on the tray present inside the upper vessel and an additional 80 ml medium was supplemented into the lower vessel. Oxygen uptake rate was improved by supplying compressed air that lifted the liquid medium into the upper vessel and touched the substrate bed. This condition probably facilitated the heat transfer to liquid medium, reduce water loss and catabolite repression. With 1% glucose supplementation, maximum alpha-amylase activity of 22 317 Ugds(-1) was produced by Aspergillus oryzae IFO 30103 within a very short incubation period (48 h) at 2 cm bed height with air flow rate of 0.1 l min(-1) g(-1) wheat bran at 32 degrees C and initial medium pH of 6. CONCLUSIONS: Within a short incubation period, significantly high alpha-amylase activity was obtained and it is higher than those reported to date at bioreactor scale operating with a fungal strain. SIGNIFICANCE AND IMPACT OF THE STUDY: The reactor is novel and can overcome some of the major problems associated with SSF process. A. oryzae IFO 30103 is reported as the best fungal source for alpha-amylase production. PMID- 22085313 TI - Radical-mediated anti-Markovnikov hydrophosphonation of olefins. AB - The radical-mediated addition of triphenylphosphonium tetrafluoroborate to olefins (hydrophosphonation) is reported. Both standard radical initiators and photochemical conditions are effective, up to the gram scale. The phosphonium salts are shown to serve as Z-selective Wittig olefination reagents, even without purification. PMID- 22085312 TI - Secondary nucleating sequences affect kinetics and thermodynamics of tau aggregation. AB - Tau protein was scanned for highly amyloidogenic sequences in amphiphilic motifs (X)(n)Z, Z(X)(n)Z (n >= 2), or (XZ)(n) (n >= 2), where X is a hydrophobic residue and Z is a charged or polar residue. N-Acetyl peptides homologous to these sequences were used to study aggregation. Transmission electron microscopy (TEM) showed seven peptides, in addition to well-known primary nucleating sequences Ac(275)VQIINK (AcPHF6*) and Ac(306)VQIVYK (AcPHF6), formed fibers, tubes, ribbons, or rolled sheets. Of the peptides shown by TEM to form amyloid, Ac(10)VME, AcPHF6*, Ac(375)KLTFR, and Ac(393)VYK were found to enhance the fraction of beta-structure of AcPHF6 formed at equilibrium, and Ac(375)KLTFR was found to inhibit AcPHF6 and AcPHF6* aggregation kinetics in a dose-dependent manner, consistent with its participation in a hybrid steric zipper model. Single site mutants were generated which transformed predicted amyloidogenic sequences in tau into non-amyloidogenic ones. A M11K mutant had fewer filaments and showed a decrease in aggregation kinetics and an increased lag time compared to wild type tau, while a F378K mutant showed significantly more filaments. Our results infer that sequences throughout tau, in addition to PHF6 and PHF6*, can seed amyloid formation or affect aggregation kinetics or thermodynamics. PMID- 22085314 TI - 120-W 2-MUm thulium:yttrium-aluminium-garnet vapoenucleation of the prostate: 12 month follow-up. PMID- 22085315 TI - Saving face, losing life: obeah pregnancy and reproductive impropriety in Southern Belize. AB - References to obeah pregnancy are widespread in southern Belize, where the belief in supernatural forces combines with Catholic teaching to create a conservative reproductive climate in which illegitimate pregnancy, reproductive misfortunes and maternal death are located in a discourse of shame. Obeah pregnancy is said to result when spiritual forces are unleashed through malicious human intent, causing bodily changes that resemble pregnancy. Death of the woman, however, usually occurs before prenatal confirmation; thus it is often unclear if an obeah pregnancy is a viable pregnancy or some other biomedical - or metaphysical - condition. This paper provides a case study of Petrona, whose story is unique in that she does not die from her purported obeah pregnancy; rather, she lives to bear the consequences of her reproductive behaviours that resulted in the stillbirth of a full-term foetus. Petrona was a traditional birth attendant who is trained to uphold biomedical antenatal protocols. Arguing that Petrona was not adequately educated to fulfill her own prenatal obligations, health care personnel sanctioned Petrona's midwifery practice and left her to process her 'shameful' situation. Ultimately, Petrona's story complicates the culturally disengaged narratives of maternal health and highlights the schism between medical knowledge and socioculturally influenced embodied experience. PMID- 22085316 TI - Effect of two intensive statin regimens on progression of coronary disease. AB - BACKGROUND: Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein (LDL) cholesterol. However, few studies have either assessed the ability of intensive statin treatments to achieve disease regression or compared alternative approaches to maximal statin administration. METHODS: We performed serial intravascular ultrasonography in 1039 patients with coronary disease, at baseline and after 104 weeks of treatment with either atorvastatin, 80 mg daily, or rosuvastatin, 40 mg daily, to compare the effect of these two intensive statin regimens on the progression of coronary atherosclerosis, as well as to assess their safety and side-effect profiles. RESULTS: After 104 weeks of therapy, the rosuvastatin group had lower levels of LDL cholesterol than the atorvastatin group (62.6 vs. 70.2 mg per deciliter [1.62 vs. 1.82 mmol per liter], P<0.001), and higher levels of high-density lipoprotein (HDL) cholesterol (50.4 vs. 48.6 mg per deciliter [1.30 vs. 1.26 mmol per liter], P=0.01). The primary efficacy end point, percent atheroma volume (PAV), decreased by 0.99% (95% confidence interval [CI], -1.19 to -0.63) with atorvastatin and by 1.22% (95% CI, -1.52 to -0.90) with rosuvastatin (P=0.17). The effect on the secondary efficacy end point, normalized total atheroma volume (TAV), was more favorable with rosuvastatin than with atorvastatin: -6.39 mm(3) (95% CI, -7.52 to -5.12), as compared with -4.42 mm(3) (95% CI, -5.98 to -3.26) (P=0.01). Both agents induced regression in the majority of patients: 63.2% with atorvastatin and 68.5% with rosuvastatin for PAV (P=0.07) and 64.7% and 71.3%, respectively, for TAV (P=0.02). Both agents had acceptable side-effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events. CONCLUSIONS: Maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Despite the lower level of LDL cholesterol and the higher level of HDL cholesterol achieved with rosuvastatin, a similar degree of regression of PAV was observed in the two treatment groups. (Funded by AstraZeneca Pharmaceuticals; ClinicalTrials.gov number, NCT000620542.). PMID- 22085318 TI - Niacin at 56 years of age--time for an early retirement? PMID- 22085317 TI - Comparative effectiveness of weight-loss interventions in clinical practice. AB - BACKGROUND: Obesity and its cardiovascular complications are extremely common medical problems, but evidence on how to accomplish weight loss in clinical practice is sparse. METHODS: We conducted a randomized, controlled trial to examine the effects of two behavioral weight-loss interventions in 415 obese patients with at least one cardiovascular risk factor. Participants were recruited from six primary care practices; 63.6% were women, 41.0% were black, and the mean age was 54.0 years. One intervention provided patients with weight loss support remotely--through the telephone, a study-specific Web site, and e mail. The other intervention provided in-person support during group and individual sessions, along with the three remote means of support. There was also a control group in which weight loss was self-directed. Outcomes were compared between each intervention group and the control group and between the two intervention groups. For both interventions, primary care providers reinforced participation at routinely scheduled visits. The trial duration was 24 months. RESULTS: At baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) for all participants was 36.6, and the mean weight was 103.8 kg. At 24 months, the mean change in weight from baseline was -0.8 kg in the control group, -4.6 kg in the group receiving remote support only (P<0.001 for the comparison with the control group), and -5.1 kg in the group receiving in-person support (P<0.001 for the comparison with the control group). The percentage of participants who lost 5% or more of their initial weight was 18.8% in the control group, 38.2% in the group receiving remote support only, and 41.4% in the group receiving in-person support. The change in weight from baseline did not differ significantly between the two intervention groups. CONCLUSIONS: In two behavioral interventions, one delivered with in person support and the other delivered remotely, without face-to-face contact between participants and weight-loss coaches, obese patients achieved and sustained clinically significant weight loss over a period of 24 months. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00783315.). PMID- 22085319 TI - Obesity treatment in primary care--are we there yet? PMID- 22085320 TI - Needed: pragmatic clinical trials for statin-intolerant patients. PMID- 22085321 TI - Attention in children and adolescents with headache. AB - OBJECTIVE: The previous studies reporting consistent visual reaction times slowing in patients with migraine prompted us to verify if headache could be associated to a broader impairment of attention. This study aims to undertake a thorough investigation of attentional performance by extending the evaluation to children with primary headache of different types. METHODS: We compared 62 children with headache (14 migraineurs with aura, 29 without aura and 19 with tension type headache) and 52 controls without headache, matched for age, sex, and intelligence using Conners' Continuous Performance Test. RESULTS: The 3 clinical groups did not differ in attentional measures. The headache patients, collapsed in 1 single sample, had mean scores in Hit Reaction Time significantly different from those of controls and also had a higher percentage of atypical scores in 2 indices of the Conners' Continuous Performance Test (faster mean reaction time and more commissions). CONCLUSIONS: Our results confirm the presence of an association between attentional problems and headache that may impact academic learning and daily activities on the long term. The finding that the 3 clinical groups did not show significant differences in attentional performance supports the hypothesis that migraine and tension headache form a continuum that may share the same pathophysiological mechanisms. These results are discussed considering that neurotransmitters and the cerebral circuits subserving headache, personality profile, and attention could overlap, thus predisposing these children to even mild attention malfunctioning. PMID- 22085322 TI - Motor skill assessment of children: is there an association between performance based, child-report, and parent-report measures of children's motor skills? AB - Client-centered practice requires therapists to actively seek the perspectives of children and families. Several assessment tools are available to facilitate this process. However, when evaluating motor skill performance, therapists typically concentrate on performance-based assessment. To improve understanding of the information provided by the different approaches, the study investigated correlations between performance-based, child-report, and parent-report measures of children's motor skill performance. A sample of convenience of 38 children 8 12 years of age with no history of motor or intellectual impairments and their parents was recruited from Victoria, Australia. Scores for the Bruininks Oseretsky Test of Motor Proficiency (performance-based, administered by a therapist), Physical Self-Description Questionnaire (child report), and Movement Assessment Battery for Children Checklist (parent report) were analyzed using Spearman's rho correlation. Several significant moderate-to-large correlations were found between scores for parent-report and scores for performance-based assessments, while few significant correlations were found between scores for child report and scores for the other two measures. The results suggest that children offer a unique perspective which should be integrated with other sources of information to gain a more holistic perspective of their motor skill performance. PMID- 22085323 TI - Lenalidomide in multiple myeloma: current experimental and clinical data. AB - Lenalidomide (LEN) is a structural analogue of Thalidomide and is currently considered a promising compound among immunomodulatory drugs. Following the demonstration of its potent anti-angiogenic, anti-inflammatory, and antineoplastic effects in preclinical models, LEN has emerged as an interesting option for the management of selective hematologic malignancies and may also have a possible role in certain solid tumors as well. It is currently approved in the second-line therapy of multiple myeloma (MM) as well as in myelodysplastic syndrome characterized by 5q minus abnormalities. LEN has been found to be effective in the treatment of both of these conditions and to possess a manageable toxicity profile. In MM, a number of ongoing clinical trials are defining its role in the treatment of newly diagnosed disease as well as in maintenance therapy. Combination approaches pretransplant have shown great promise. Its role in the management of relapsed and refractory disease is now well established. Its long-term tolerability profile appears favorable although an increased risk in new malignancies in patients receiving LEN as maintenance post-stem cell transplant warrants some caution, with follow-up studies being important in determining the long-term implications of this observation. PMID- 22085324 TI - Comparison of polyphenol extractions from olive pomace and solid fraction of olive mill waste water. AB - The solid fraction of olive mill waste water (OMWW) was separated from OMWW and then the solutes in the solid fraction of OMWW were extracted with ethanol. The detection of polyphenols in the ethanol extract showed the presence of polyphenols in the solid fraction of OMWW. Effects of solvent-to-solid ratio, extraction and agitation time on the extraction of polyphenols from the solid fraction of OMWW were examined and the maximum amount of polyphenol was extracted from the solid fraction of OMWW with a solvent-to-solid ratio of 15 at 70 min of extraction and 10 min of agitation time. Percent yields and purities of the polyphenols extracted from solid fraction of OMWW were higher than those of the polyphenols extracted from olive pomace with ethanol at 70 min of extraction and 10 min of agitation time with solvent-to-solid ratio of 15. PMID- 22085325 TI - Social assistance needs of children with chronic health conditions: a comparative study of international and South african eligibility assessment instruments. AB - The efficacy of the current instrument to assess the social assistance needs of children with chronic health conditions in South Africa is questioned. To develop an improved assessment instrument for South African use, this instrument was pitted against two international social assistance assessment instruments, the United Kingdom (UK) Disability Living Allowance (DLA) and the Australian Child Disability Assessment Tool (CDAT). A purposive sample of 18 children representing six types of disability and chronic illnesses was selected, and all three assessment instruments were used to assess the needs of these children. A juxtaposition of the outcomes of the assessment instruments revealed significant differences. The South African instrument deemed the majority (56%) of the sample ineligible for assistance. On the contrary, significant majorities were deemed eligible for assistance in terms of the U.K. (94%) and Australian (89%) instruments. The study recommended that a holistic approach to need assessment be adopted in the design of a more appropriate assessment instrument for South African use. PMID- 22085326 TI - Actualizing a provider alliance to expand health services access to a low-income urban community. AB - Social change to facilitate health care access for vulnerable populations sometimes involves model-driven innovative structures and innovative planning and implementation approaches. This paper described and analyzed the rationale, conceptual framework, program components, and implementation of the South Central Health Care Alliance (SCHCA) implemented in South Los Angeles from January 2002 to December 2004. The program development and implementation was guided by an integrated framework linking the Open Systems Theory, the Social Cognitive Theory, the Health Belief Model, and the Preventive Health Education and Medical Home Project. The performance of the SCHCA as a social system, partnership, and participatory implementation program is also presented. While the SCHCA was found to be a dynamic social system that responded well to contingencies, its performance as a partnership and participatory implementation program was wanting in many respects. PMID- 22085327 TI - Health system factors affecting communication with pediatricians: gendered work culture in primary care. AB - This qualitative study examined the roles that practice setting, education level, and gender may play in social workers' communication satisfaction with pediatricians. Taking an ethnographic approach, the researcher interviewed social workers and pediatricians who worked together to provide mental health services in primary care. The results suggested that gender at the health system level may be an issue and that gendered work culture in primary care was a factor in communication. In particular, reimbursement, an aspect of the gendered work culture, was a substantial communication barrier, and the implications for Medicaid billing are discussed. PMID- 22085328 TI - Factors associated with toothache among African American adolescents living in rural South Carolina. AB - The aim of this study is to explore behavioral factors associated with toothache among African American adolescents living in rural South Carolina. Using a self administered questionnaire, data were collected on toothache experience in the past 12 months, oral hygiene behavior, dental care utilization, and cariogenic snack and nondiet soft drink consumption in a convenience sample of 156 African American adolescents age 10 to 18 years living in rural South Carolina. Univariable and multivariable logistic regression analyses were used to assess the associations between reported toothache experience and sociodemographic variables, oral health behavior, and snack consumption. Thirty-four percent of adolescents reported having toothache in the past 12 months. In univariable modeling, age, dental visit in the last 2 years, quantity and frequency of cariogenic snack consumption, and quantity of nondiet soft drink consumption were each significantly associated with experiencing toothache in the past 12 months (all p values < 0.05). Multivariable logistic regression analysis indicated that younger age, frequent consumption of cariogenic snacks, and number of cans of nondiet soft drink consumed during the weekend significantly increased the odds of experiencing toothache in the past 12 months (all p values <= 0.01). Findings indicate age, frequent consumption of cariogenic snacks, and number of cans of nondiet soft drinks are related to toothache in this group. Public policy implications related to selling cariogenic snacks and soft drink that targeting children and adolescents especially those from low income families are discussed. PMID- 22085330 TI - HIV risk among female sex workers in Miami: the impact of violent victimization and untreated mental illness. AB - Street-based female sex workers constitute a vulnerable population for HIV, as they are often enmeshed in chronic patterns of substance use, sexual risk, homelessness, and violent victimization. This study examined the specific contributions of victimization history and abuse-related traumagenic factors to mental health functioning and sexual risk behaviors, while considering the impact of environmental risk factors as well. Using targeted sampling strategies, we enrolled 562 Miami-based female sex workers into an intervention trial testing the relative effectiveness of two alternative case management conditions in establishing linkages with health services and reducing risk for HIV. Lifetime prevalence of abuse was extremely elevated at 88%. Nearly half reported abuse before the age of 18, while 34% reported violent encounters with "dates" or clients in the past 90 days. Serious mental illness (SMI) was quite common, with 74% reporting severe symptoms of depression, anxiety, or traumatic stress. For those with histories of abuse, SMI appeared to mediate the association between abuse-related trauma and unprotected sex behaviors. Mental health treatment would appear to be an important component of effective HIV prevention among this vulnerable group, and should form part of a compendium of services offered to female sex workers. PMID- 22085331 TI - Foldamer structuring by covalently bound macromolecules. AB - We used fluorescence and electronic absorption spectroscopy to study the molecular weight dependence of macromolecule-induced folding in a chain-centered meta-phenylene ethynylene (mPE) oligomer. Analogous to the ability of intrinsically unstructured proteins (IUPs) to induce folding of globular proteins in cellular environments, we show that macromolecules attached to both ends of an mPE dodecamer induce the foldamer to collapse into a presumed helical conformation. The collapse is especially prominent once the macromolecule segments become larger than ca. 50 kDa. For sufficiently large macromolecules, the conformational structuring occurs even in solvents that normally denature the foldamer. Based on these findings, chain-centered foldamers might find use as models to investigate the fundamental macromolecular physics of IUPs. PMID- 22085332 TI - 'Let's have it tested first': choice and circumstances in decision-making following positive antenatal screening in Hong Kong. AB - There now exists a considerable body of sociological work examining antenatal screening for fetal abnormalities. A common theme emerging from this literature is that pregnant women report not feeling able to exercise choice freely, experiencing constraints both from medical professionals and their perceived expectations of the sociocultures in which they live. This study adds to existing literature in three ways. Firstly, in contrast to the existing body of interview based research, the study uses video recordings of actual consultations, in order to capture the interactional processes through which choice and constraints are established, negotiated and contested. Secondly, it explores the next stage in the process of antenatal screening, by focusing on women who are offered invasive diagnostic testing as a result of 'high risk' screening results, and who have been the subject of little research. Thirdly, the study site in Hong Kong provides a particularly interesting location, given limited research on antenatal screening in that part of the world, and Hong Kong's cosmopolitan environment that is reflected in the diversity of client population undergoing antenatal screening. Using conversation analysis we examine how aspects of the clients' diverse socioeconomic backgrounds and circumstances are interactionally managed in this setting, and how this might impact on decision-making. PMID- 22085333 TI - Effects of bulk colloidal stability on adsorption layers of poly(diallyldimethylammonium chloride)/sodium dodecyl sulfate at the air-water interface studied by neutron reflectometry. AB - We show for the oppositely charged system poly(diallyldimethylammonium chloride)/sodium dodecyl sulfate that the cliff edge peak in its surface tension isotherm results from the comprehensive precipitation of bulk complexes into sediment, leaving a supernatant that is virtually transparent and a depleted adsorption layer at the air/water interface. The aggregation and settling processes take about 3 days to reach completion and occur at bulk compositions around charge neutrality of the complexes which lack long-term colloidal stability. We demonstrate excellent quantitative agreement between the measured surface tension values and a peak calculated from the surface excess of surfactant in the precipitation region measured by neutron reflectometry, using the approximation that there is no polymer left in the liquid phase. The nonequilibrium nature of the system is emphasized by the production of very different interfacial properties from equivalent aged samples that are handled differently. We go on to outline our perspective on the "true equilibrium" state of this intriguing system and conclude with a comment on its practical relevance given that the interfacial properties can be so readily influenced by the handling of kinetically trapped bulk aggregates. PMID- 22085334 TI - Serpin protease inhibitors in plant biology. AB - Protease inhibitors of the serpin family are ubiquitous in the plant kingdom but relatively little is known about their biological functions in comparison with their counterparts in animals. X-ray crystal structures have provided crucial insights into animal serpin functions. The recently solved structure of AtSerpin1 from Arabidopsis thaliana, which has the highly conserved reactive center P2-P1' Leu-Arg-Xaa (Xaa = small residue), displays both conserved and plant-specific serpin features. Sequence homology suggests that AtSerpin1 belongs to serpin Clade B, composed of intracellular mammalian serpins, which is consistent with the lack of strong evidence for secretion of serpins from plant cells. The major in vivo target protease for AtSerpin1 is the papain-like cysteine RD21 protease, a match reminiscent of the inhibition of cathepsins K, L and S by the Clade-B mammalian serpin, SCCA-1 (SERPINB3). The function of AtSerpin1 and other serpins that contain P2-P1' Leu-Arg-Xaa (the 'LR' serpins) in plants remains unknown. However, based on its homology and interactive partners, AtSerpin1 and perhaps other serpins are likely to be involved in regulating programmed cell death or associated processes such as senescence. Abundant accumulation of serpins in seeds and their presence in phloem sap suggest additional functions in plant defense by irreversible inhibition of digestive proteases from pests or pathogens. Here we review the most recent findings in plant serpin biology, focusing on advances in describing the structure and inhibitory specificity of the LR serpins. PMID- 22085335 TI - Impact of insulin pumps on glycaemic control in a pump-naive paediatric regional population. AB - AIM: To examine the clinical impact of insulin-pump therapy for children with type 1 diabetes mellitus (T1DM) in a regional paediatric service, Auckland, New Zealand. METHODS: Retrospective analysis of children with T1DM from the Starship paediatric diabetes database who started on insulin-pump therapy from 2002 to 2008 compared with the whole T1DM population and with an equal number of non-pump patients matched by age, sex, ethnicity and duration of diabetes. RESULTS: From 621 subjects with 6680 clinic visits, 75 children were treated with insulin-pump therapy for more than 12 months. Transitioning to insulin-pump treatment was associated with an improvement in HbA1c compared with baseline (-0.3%/year, P < 0.001) for up to 3 years. In contrast, despite similar deprivation scores, non pump controls showed a continuing trend to higher HbA1C values (+0.2%/year, P < 0.01). The risk of severe hypoglycaemia fell after pump start (from 27 (0-223) to 5 (0-0.91) events/100 patient years) with no change in non-pump controls; the rate of diabetic ketoacidosis remained low in both groups. CONCLUSIONS: In a pump naive regional paediatric population, insulin-pump therapy for T1DM was safe and effective, and associated with sustained improvements in HbA1c and lower risk of hypoglycaemia. PMID- 22085336 TI - The possibility of using cyanobacterial bloom materials as a medium for white rot fungi. AB - AIMS: The present study was conducted to evaluate the possibility of using cyanobacterial bloom materials as a medium for white rot fungi and the capability of white rot fungi, Trichaptum abietinum 1302BG and Lopharia spadicea to biodegrade dried cyanobacterial bloom material taken from Taihu Lake. METHODS AND RESULTS: The results showed T. abietinum 1302BG and L. spadicea could use the cyanobacterial bloom materials taken from Taihu Lake for growth to measure the mycelial plaque and dry-weight mycelial pellicles of fungi. The removal rate of dried cyanobacterial bloom materials incubated with white rot fungi is approximately 100%. CONCLUSIONS: The cyanobacterial bloom material can be used as a glucose substitute in white rot fungi medium. The white rot fungi, T. abietinum 1302BG and L. spadicea, can also directly decrease the biomass of cyanobacterial bloom material taken from Taihu Lake. SIGNIFICANCE AND IMPACT OF THE STUDY: Cyanobacterial bloom thrives in eutrophic fresh waters all over the world. Micro-organisms, particularly fungi, have attracted attention as possible agents for the degradation of phytoplankton species. Dealing with cyanobacterial bloom material as a medium for fungi instead of directly discharging them as organic fertilizers is a new, safe and environmentally friendly approach. PMID- 22085337 TI - Escherichia coli SlyD, more than a Ni(II) reservoir. AB - SlyD interacts with HypB and contributes to nickel insertion during [NiFe] hydrogenase biogenesis. Herein, we provide evidence of SlyD acting as a nickel storage determinant in Escherichia coli and show that this Ni(II) can be mobilized to HypB in vitro even under competitive conditions. Furthermore, SlyD enhances the GTPase activity of HypB, and acceleration of release of Ni(II) from HypB is more pronounced when HypB is GDP-bound. The data support a model in which a HypB-SlyD complex establishes communication between GTP hydrolysis and nickel delivery and provide insight into the role of the HypB-SlyD complex during [NiFe] hydrogenase biosynthesis. PMID- 22085338 TI - Risk profile of bevacizumab in patients with non-small cell lung cancer: a meta analysis of randomized controlled trials. AB - BACKGROUND: Severe adverse events (AEs) have been reported in cancer patients treated with bevacizumab. Currently, safety of bevacizumab in patients with non small cell lung cancer (NSCLC) is not clear. We conducted a meta-analysis to evaluate the risk profile of bevacizumab in NSCLC patients. METHODS: Relevant trials were identified by searching databases and conference proceedings. Data on treatment-related deaths and grade 3 or 4 AEs were extracted and pooled to calculate relative risks (RRs) with 95% confidence interval (CI) for bevacizumab compared with chemotherapy alone. RESULTS: A total of 2210 patients were included in the analysis. Compared with chemotherapy alone, high-dosage (15 mg/kg) bevacizumab was associated with an increased risk of treatment-related deaths (RR = 2.04, 95% CI = 1.18-3.52), but not for low-dosage (7.5 mg/kg) group (RR = 1.20, 95% CI = 0.60-2.41). In addition, treatment with bevacizumab was associated with several grade 3 or 4 AEs in patients with NSCLC, especially in high-dosage bevacizumab group. CONCLUSION: The use of the bevacizumab increases the risk of treatment-related deaths and several grade 3 or 4 AEs in patient with NSCLC. The risk may be dose-dependent. Close monitoring and adequate management are recommended to decrease severe AEs. PMID- 22085339 TI - Mechanistic analysis of muraymycin analogues: a guide to the design of MraY inhibitors. AB - The systematic structure-activity relationship (SAR) of the muraymycins (MRYs) using an Ugi four-component reaction (U4CR) was investigated. The impact of the lipophilic substituent on antibacterial activity was significant, and the analogues 8 and 9 having a lipophilic side chain exhibited good activity against a range of Gram-positive bacterial pathogens, including MRSA and VRE. Further investigation of compounds 8 and 9 revealed these analogues to be selective inhibitors of the MraY transferase and nontoxic to HepG2 cells. The SAR of the accessory urea-peptide moiety indicated that it could be simplified. Our SAR study of the MRYs suggests a probable mechanism for inhibition of the MraY, where the inner moiety of the urea-dipeptide motif interacts with the carbohydrate recognition domain in the cytoplasmic loop 5. The predicted binding model would provide further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on MRYs. PMID- 22085340 TI - Au-catalyzed piperidine synthesis via tandem acyloxy migration/intramolecular [3 + 2] cycloaddition of enynyl esters. AB - An Au-catalyzed tandem protocol involving enynyl ester isomerization and subsequent intramolecular [3 + 2] cyclization has been developed. This strategy provides an efficient approach for the synthesis of polyfunctional piperidines, which are subunits of many bioactive molecules. PMID- 22085341 TI - Atrophy of corrugator supercilii muscle in a patient induced by the onabotulinum toxin injection. AB - Onabotulinum toxin has been used to treat a variety of headaches. We report a case of a 29-year-old woman who developed temporary and reversible atrophy of corrugator supercilii muscle after onabotulinum toxin (Botox, Allergan, Irvine, CA, USA) injection. To our best knowledge this has not been described in the literature before. PMID- 22085342 TI - Gender differences in mobility disability during young, middle and older age in West African adults. AB - The objective of this study was to assess the prevalence and the contribution of socio-demographic factors and chronic diseases to mobility disability in West African countries. Data were obtained from the World Health Survey (2002-2003) in which adults>=18 years participated, from Burkina Faso (n=4822), Mali (n=4230) and Senegal (n=3197). Participants reporting mild, moderate, severe, extreme difficulty or inability to move around were defined as having mobility disability. All estimates were corrected for sampling design. Association measures were estimated using logistic regression methods. Mobility disability was frequent at young ages (35-44 years old) in men and women, respectively: 17% and 23% in Burkina Faso, 12% and 23% in Mali and 22% and 34% in Senegal. Women had higher odds of mobility difficulty than men at every age group in the three countries: 1.34 (95%CI 1.06; 1.70) in Burkina Faso; 2.33 (95% CI 1.84; 2.71) in Mali and 1.82 (95%CI 1.41; 2.36) in Senegal. Controlling for socio-economic factors and chronic disease, these odds changed respectively to 0.94 (95%CI 0.70; 1.25), 2.19 (95%CI 1.61; 2.96) and 1.90 (95%CI 1.27; 2.84). These results constitute a benchmark for the study of trends of mobility disability in West Africa and could be used by policy planners. PMID- 22085344 TI - The patient, the physician and the technician. PMID- 22085345 TI - Effectiveness and safety of posterior titanium instrumentation in children with adolescent idiopathic scoliosis: a prospective study. AB - OBJECTIVES: This study aims to determine the effectiveness and the relative safety of posterior spinal fusion with titanium instrumentation in children with adolescent idiopathic scoliosis (AIS). PATIENTS AND METHODS: A prospective cohort (case-only) study was conducted to determine this effectiveness and safety. There were 24 patients (21 girls, 3 boys; mean age 14.1+/-1.8 years; range 11 to 17 years) who underwent surgery between January 2002 and December 2003 in our clinic, with a minimum of two years follow-up. Upper thoracic, thoracic, and thoracolumbar coronal curves as well as kyphosis from T5-T12 were measured as main outcome variables and repeated measure ANOVA was used to assess the data. RESULTS: The main thoracic curve (coronal plane) correction achieved at the first erect period (the first 4 weeks postoperative) (mean 12.21+/-9.78 degrees), this correction was maintained at 24 months follow-up (mean 15.71+/-7.15 degrees) and both were significantly lower than the preoperative values (mean 57.0+/-12.75 degrees), (p<0.001). Sagittal plane (kyphosis angle between T5-T12) curve was not worsened by posterior titanium instrumentation and it was 19.50+/-10.53 degrees preoperatively, 16.45+/-6.68 degrees at the first erect period and 17.73+/-8.40 degrees at the 24 months follow-up (p=0.74). There were no evidence of pseudoarthrosis, no loss of correction and no infections. CONCLUSION: Posterior titanium instrumentation in the treatment of AIS is effective due to its ability to achieve and maintain curve correction. Further, this instrumentation does not worsen hypokyphosis and is safe since there were no adverse events. PMID- 22085346 TI - [The relationship between chronic hip pain and femoroacetabular impingement: an evaluation with clinical signs and radiography]. AB - OBJECTIVES: In this study, we investigated the rate of the clinical and radiographic findings of femoroacetabular impingement (FAI) in patients with chronic hip pain and compared the findings with those of a control group. PATIENTS AND METHODS: The clinical and radiographic findings of FAI in 38 patients (group 1) having hip pain for more than three months were analyzed and compared with 42 controls (group 2). Internal rotation degrees were measured while the hips were at 90 degrees flexion and impingement test was performed by rotating the hips internally at 90 degrees flexion and adduction. The FAI findings were investigated on anteroposterior pelvis radiographs and cross-table lateral radiographs of the hip joint in both groups. The collum-diaphyseal angle, alpha angle and anterior offset ratio on the femoral side and the center-edge angle, acetabular index, extrusion index and crossover sign on the acetabular side were evaluated. RESULTS: The internal rotation degree of the painful hips were less than 20 degree in 18 (47.4%) patients in group 1 and in one (2.4%) patient in group 2 (p<0.001). The impingement sign was positive in 15 (39.5%) patients in group 1 and in one (2.4%) patient in group 2 (p<0.001). While the rate of radiographic findings that can cause pincer type FAI were same in both groups, the rate of patients with radiographic findings that can cause cam type FAI was 76.3% (n=29) in group 1 and 42.9% (n=18) in group 2 (p=0.002). CONCLUSION: Femoroacetabular impingement is one of the causes of chronic hip pain and if evaluated with suitable clinical and radiographic parameters, the rates of diagnosis may increase. PMID- 22085347 TI - [Comparison of the results of supervised physiotherapy program and home-based exercise program in patients treated with arthroscopic-assisted mini-open rotator cuff repair]. AB - OBJECTIVES: This study aims to compare the results of supervised exercise program versus standardized home based exercise program after rotator cuff repair with respect to severity of pain, functional status, quality of life, and depression. PATIENTS AND METHODS: Twenty-eight patients (5 males, 23 females; mean age 59.8+/ 9.1 years; range 40 to 83 years) who had rotator cuff repair were evaluated. Patients were divided into two groups and the first group was treated with supervised physiotherapy (n=15) and the second group was treated with home-based exercise program (n=13). Pendulum exercises and passive exercises within pain limits were performed by all patients in the six-week immobilization period with shoulder sling with abduction pillow after rotator cuff repair. After this period, the patients in home-based exercise program were taught to perform active exercises and the patients in supervised physiotherapy group were treated with active shoulder range of motion exercises under the supervision of the physiotherapist. When patients reached to active full range of motion, strengthening exercises were added to exercise program. Patients were assessed preoperatively and at the end of the postoperative third month. Pain was evaluated with visual analog scale (VAS), functional status with Constant shoulder score, quality of life with short form-36 (SF-36), and depressive symptoms with Beck depression inventory (BDI). RESULTS: There were significant improvements in all evaluation parameters in both groups after rotator cuff repair. CONCLUSION: There were no statistical differences between the patients who received exercise program under the supervision of the physiotherapist and the patients who were treated with standardized home-based exercise program for the efficacy of treatment in the evaluation of pain, functional status, quality of life, and depression status. When the rehabilitation programs were analyzed for cost effectiveness, the supervised physiotherapy group was found to have higher costs. PMID- 22085348 TI - Relationship between clinical and electrophysiological results in surgically treated carpal tunnel syndrome. AB - OBJECTIVES: In this study, relationship between clinical and electrophysiological results of decompression via mini incision technique was investigated. PATIENTS AND METHODS: Thirty-nine hands of 38 patients (35 females, 3 males; mean age 54.8 years; range 33 to 81 years) with carpal tunnel syndrome who were treated surgically in our clinic between April 2004 and February 2009 were included into the study. Patients were evaluated clinically and electrophysiologically both in pre- and postoperative period. RESULTS: There was a difference between pre- and postoperative clinical results (p=0.00). Clinically, the mean symptom severity and functional status scores were decreased in 36 hands (92.3%). Postoperative electrophysiological grades were significantly improved compared to the preoperative ones. There was a significant difference between the pre- and postoperative clinical scores in all of the preoperative electromyography grades, except for the moderate grades. However, no relation was found between the electrophysiological grades and the clinical results in both pre- and postoperative period. CONCLUSION: This study shows that in spite of clinical improvement after carpal tunnel syndrome surgery through mini incision technique, electrophysiological findings were still suggesting the presence of varying degrees of carpal tunnel syndrome in postoperative period. PMID- 22085349 TI - Correlation between selective pedobarographic and radiographic measures in the assessment of surgically treated CTEV patients. AB - OBJECTIVES: This study aims to assess the correlation between selective pedobarographic and radiographic measures in patients with surgically treated congenital talipes equinovarus (CTEV). PATIENTS AND METHODS: We examined 50 patients [70 feet; 34 girls (68%) and 16 boys (32%); mean age 11.2 months; range 3-30.6 months] surgically treated for CTEV with a mean follow-up of 8.7 years (range 4.3 to 15 years). Patients had radiographic and pedobarographic measurements simultaneously. The right and left feet were assessed separately. The relationship between selective pedobarographs and standing weight-bearing radiographs of the foot was assessed by the Pearson's correlation coefficient and the Spearman's rank correlation coefficient. RESULTS: There were moderate correlations between selective pedobarographic and radiographic measures in surgically treated CTEV patients. The strongest positive correlations were between the right heel rise and right anteroposterior calcaneal-5(th) metatarsal angle (r=0.54, p=0.001) and, the right anteroposterior talo-1(st) metatarsal angle (r=0.48, p=0.003). A similar strong positive correlation was observed between lateral tibiocalcaneal angle and left heel rise parameters (r=0.42, p=0.01). CONCLUSION: There were moderate correlations between selective pedobarographic and radiographic measures of surgically treated CTEV. However, the pedobarographic measure is a direct measure of the contact force of the foot with the ground and therefore has a more direct functional implication than radiographic measures. PMID- 22085350 TI - [Effect of bone cement application on the incidence of deep vein thrombosis in major joint arthroplasties]. AB - OBJECTIVES: In this study, we have investigated whether the application of bone cement has an effect on the frequency of deep vein thrombosis (DVT) in major joint arthroplasties (MJA). PATIENTS AND METHODS: A total of 95 MJA cases meeting the inclusion criteria of this study between January 2004 and January 2005 were divided into cemented and cementless groups. For prophylaxis, all patients were given low molecular weight heparin (LMWH). The patients were scanned for DVT preoperatively and on the postoperative 12(th) day by color Doppler ultrasonography. RESULTS: In hip arthroplasties, in knee arthroplasties and in general, DVT was seen more frequently in cemented group, however, there was no statistically significant difference between groups in the frequency of DVT (p=0.549, p=0.749 and p=0.462, respectively). Also, there was no significant difference between the results of the different LMWH groups (p=0.616). CONCLUSION: The results of this study shows that bone cement application in MJAs such as hip or knee arthroplasties has no significant effect on the frequency of DVT. PMID- 22085351 TI - Football injuries on synthetic turf fields. AB - OBJECTIVES: Football injuries that occur during football matches played on synthetic fields and the features of these injuries were investigated and the data was pursued for the prevention and reduction of these injuries. PATIENTS AND METHODS: All adolescent and adult trauma cases who admitted to the Emergency Department with football injuries on synthetic fields were retrospectively investigated. Nine hundred and eighty-five male cases were detected with a mean age of 30.1+/-4.2 years (range 15-57 years). Age, gender, times of admittance to the Emergency Department, site of injury, type of injury, and clinical result data of the cases were examined. RESULTS: 19:00 to 24:00 hours (n=852, 86.5%) and weekdays were the most frequent admittance times. It was detected that lower extremities (n=583, 59.2%) were the most commonly affected body parts and the upper-extremity injuries (n=281, 28.6%) and the head and neck injuries (n=75, 7.6%) were the second and third most commonly seen injuries, respectively.The most frequently observed injury types were contusions, abrasions and hematomas in all cases (n=364, 37.0%). Sprains/strains were the second most common types of injuries (n=343, 34.8%). When the final diagnoses of all cases were examined, it was determined that the anterior talofibular ligament injuries were the second most frequent after soft-tissue injuries (n=217, 22%). CONCLUSION: Football matches on synthetic fields can lead to serious orthopedic injuries. Investigation of the mechanisms of these injuries, which cause workday and economic losses, will be a guide for the future studies on the prevention of these injuries. PMID- 22085343 TI - Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. AB - BACKGROUND: In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol is superior to simvastatin alone in reducing such residual risk. METHODS: We randomly assigned eligible patients to receive extended-release niacin, 1500 to 2000 mg per day, or matching placebo. All patients received simvastatin, 40 to 80 mg per day, plus ezetimibe, 10 mg per day, if needed, to maintain an LDL cholesterol level of 40 to 80 mg per deciliter (1.03 to 2.07 mmol per liter). The primary end point was the first event of the composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, hospitalization for an acute coronary syndrome, or symptom driven coronary or cerebral revascularization. RESULTS: A total of 3414 patients were randomly assigned to receive niacin (1718) or placebo (1696). The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy. At 2 years, niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter (0.91 mmol per liter) to 42 mg per deciliter (1.08 mmol per liter), lowered the triglyceride level from 164 mg per deciliter (1.85 mmol per liter) to 122 mg per deciliter (1.38 mmol per liter), and lowered the LDL cholesterol level from 74 mg per deciliter (1.91 mmol per liter) to 62 mg per deciliter (1.60 mmol per liter). The primary end point occurred in 282 patients in the niacin group (16.4%) and in 274 patients in the placebo group (16.2%) (hazard ratio, 1.02; 95% confidence interval, 0.87 to 1.21; P=0.79 by the log rank test). CONCLUSIONS: Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter (1.81 mmol per liter), there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period, despite significant improvements in HDL cholesterol and triglyceride levels. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; AIM-HIGH ClinicalTrials.gov number, NCT00120289.). PMID- 22085352 TI - Effect of pentoxifylline on fracture healing: an experimental study. AB - OBJECTIVES: This study aims to investigate the effect of pentoxifylline on fracture healing in an experimental animal model. MATERIALS AND METHODS: Sixty one male, Wistar-Albino rats were divided randomly into two groups as the pentoxifylline and control groups. Standard, closed femoral shaft fractures were established in all rats using a three-point bending device under general anesthesia. The rats were administered either pentoxifylline or isotonic NaCl injections everyday, beginning after production of fracture until they were sacrificed. Ten rats (11 rats in the pentoxifylline group on the 14(th) day) in each group were sacrificed on the 7(th), 14(th) and the 21(st) days and clinical, radiological, and histological examinations were performed to evaluate bony union. RESULTS: Radiological evaluation of callus did not reveal any significant difference between the control and the pentoxifylline groups in the first, second and the third weeks. However histological callus formation was significantly superior in pentoxifylline group compared to the control group at the end of the first week and callus formation was better in the control group in the third week. CONCLUSION: Pentoxifylline can be used to accelerate fracture union in early phases. Because of its hematological effects pentoxifylline accelerates the hematoma stage of fracture healing. But it inhibits fracture union in the later stages, presumably due to its anti-inflammatory effect. This should be taken into consideration during the clinical use of this drug. PMID- 22085353 TI - [Effects of human amniotic fluid on posterolateral spinal fusion: an experimental preliminary study]. AB - OBJECTIVES: In this study, the effects of human amniotic fluid on posterolateral spinal fusion were investigated in a rat model. MATERIALS AND METHODS: Twenty eight 20-week-old male Sprague Dawley rats were included in the study. The subjects were divided into two main groups as the control group and the amniotic fluid group. Posterolateral spinal fusion was performed by using autografts in all groups whereas 0.3 ml of centrifuged human amniotic fluid was added to the fusion area in amniotic fluid groups. Groups were further divided into subgroups each including seven rats and evaluated radiologically and histologically at the third and sixth weeks. RESULTS: The radiological fusion observed in the amniotic fluid group was significant at the sixth week when compared to that in the control group. The histological fusion quality was significant in the amniotic fluid groups both at the third and sixth weeks when compared to the control groups. CONCLUSION: We conclude that human amniotic fluid enhances posterolateral spinal fusion. We believe that the growth factors and hyaluronic acid present in the amniotic fluid played a role in this result. PMID- 22085354 TI - [Diffuse pigmented villonodular synovitis in the shoulder joint and the biceps tendon: a case report]. AB - Pigmented villonodular synovitis (PVNS) is a benign proliferative disease of synovium frequently most frequently seen in the knee joint and hand tendon synovial tissues; shoulder involvement is extremely rare. It can be seen in joints in two forms as nodular or diffuse involvement. The clinical and radiological symptoms are not specific to the disease and usually mimic other joint diseases. The general complaint of the patients is long-lasting painful swelling that could not be diagnosed. In magnetic resonance imaging it is observed as soft tissue mass. Pigment deposition and histiocytic cell infiltration in the villous synovial projections are the major histological findings. Synovectomy is performed for treatment and the incidence of recurrence is high. In this article, we report a 23-years-old male patient with diffuse PVNS in the shoulder joint and biceps tendon which are rarely involved in PVNS. PMID- 22085355 TI - Traumatic asymmetrical bilateral hip dislocation: a case report and literature review. AB - Traumatic asymmetrical bilateral dislocation of the hip joint is a rare occurrence. Herein we report a case of traumatic asymmetrical bilateral dislocation of the hip caused by a falling object. A 31-year-old healthy male was injured by a falling wall of weighing approximately 100 kg from behind in the lumbosacral area. The patient sustained a pelvic fracture, posterior dislocation of the right hip joint associated with a comminuted fracture of the right acetabulum, and anterior dislocation of the left hip joint. Manual reduction of both hip dislocations was performed in the Emergency Department. The posterior wall fracture of the right acetabulum was treated with open reduction and internal fixation by plate and screw. Reduction of both hips was successful and no femur necrosis or arthrosis was found during the four-year follow-up. Heterotopic ossification was found but it did not affect joint function. Prompt reduction of hip dislocations in the Emergency Department can reduce the incidence of avascular necrosis of the femoral head. PMID- 22085356 TI - Unusual tennis injuries: boxer's fracture and medial subtalar dislocation: report of two cases. AB - In this article, we describe two cases of unusual tennis injuries. One of them was a 48-year-old elite tennis player. He had boxer's fracture due to fall during a tennis match. The other one was a 22-year-old beginner tennis player. He had talonavicular and subtalar dislocations due to fall during tennis match caused by shoes inappropriate for tennis. Patients were treated conservatively without any complications. PMID- 22085357 TI - One new diphenylmethane glycoside from the leaves of Psidium guajava L. AB - To investigate the chemical constituents of Psidium guajava L, the EtOH/H(2)O extract of the fresh leaves was subjected to various chromatography. One diphenylmethane, one benzophenone, and eight flavonoids were isolated and elucidated as 2,6-dihydroxy-3-formaldehyde-5-methyl-4-O-(6"-O-galloyl-beta-D glucopyranosyl)-diphenylmethane (1), 2,6-dihydroxy-3,5-dimethyl-4-O-(6"-O-galloyl beta-D-glucopyranosyl)-benzophenone (2), kaempferol (3), quercetin (4), quercitrin (5), isoquercitrin (6), guaijaverin (7), avicularin (8), hyperoside (9), reynoutrin (10) by spectroscopic methods, including 1D and 2D NMR and HR-ESI MS spectrometry as well as by comparison with published data. Compounds 5 and 10 are obtained from P. guajava for the first time, and compound 1 is a new diphenylmethane compound. PMID- 22085358 TI - Experimental autoimmune encephalomyelitis--achievements and prospective advances. AB - Multiple sclerosis (MS) is an autoimmune disorder of the CNS. Different subtypes of the disease have been noted, and characterized by distinct clinical courses and histopathologic manifestations. The most intensively studied animal model of MS, experimental autoimmune encephalomyelitis (EAE), classically leads to deficits in motor functions, and is mediated by T helper cells. Recently, T(H)17 cells were ascribed an even greater pathogenic impact than T(H)1 cells, but new findings render this view controversial. Although classic EAE has been an invaluable tool, it does not cover the entire pathogenic entity of MS. Especially B-cell contribution and autoantibody-dependence are not mirrored adequately: therefore, new B-cell-dependent models, such as MP4-induced EAE, have been introduced. Furthermore, certain symptoms and the spontaneous onset of MS are not featured in classic EAE. Herein, atypical and spontaneous EAE models can be used for investigation of common symptoms, such as tremor and ataxia, as well as spontaneous disease development. MS displays a marked inter-individual heterogeneity, and no single model will be able to cover all features. Thus, depending on the objective of one's study, the appropriate EAE model has to be carefully chosen. In addition, refined models should be designed to gain a more complete understanding of MS. PMID- 22085359 TI - Vascular endothelial growth factor A protein level and gene expression in intracranial meningiomas with brain edema. AB - Meningiomas are the second most common primary intracranial tumors in adults. Although meningiomas are mostly benign, more than 50% of patients with meningioma develop peritumoral brain edema (PTBE), which may be fatal because of increased intracranial pressure. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and angiogen. VEGF-A protein, which is identical to vascular permeability factor, is a regulator of angiogenesis. In this study, 101 patients with meningiomas, and possible co-factors to PTBE, such as meningioma subtypes and tumor location, were examined. Forty-three patients had primary, solitary, supratentorial meningiomas with PTBE. In these, correlations in PTBE, edema index, VEGF-A protein, VEGF gene expression, capillary length, and tumor water content were investigated. DNA-branched hybridization was used for measuring VEGF gene expression in tissue homogenates prepared from frozen tissue samples. The method for VEGF-A analysis resembled an ELISA assay, but was based on chemiluminescence. The edema index was positively correlated to VEGF-A protein (p = 0.014) and VEGF gene expression (p < 0.05). The capillary length in the meningiomas was positively correlated to the PTBE (p = 0.038). If VEGF is responsible for the formation of PTBE, the edema may be treated with the anti-VEGF drug Bevacizumab (Avastin), which has been shown to reduce PTBE in patients with glioblastoma multiforme. PMID- 22085360 TI - Evaluating TIMP-1, Ki67, and HER2 as markers for non-sentinel node metastases in breast cancer patients with micrometastases to the sentinel node. AB - The aim was to investigate whether the biochemical prognostic markers TIMP-1, Ki67, and HER2 could predict metastatic spread to non-sentinel nodes (NSN) in breast cancer patients with micrometastases to sentinel node (SN). We included all breast cancer patients with micrometastases to SN operated between 2001 and 2007 at the Department of Breast Surgery, Herlev Hospital. The study was designed as a matched case-control study with 25 cases with micrometastases to SN and, in addition, metastatic spread to NSN and 50 matched controls with micrometastases to SN, but without NSN metastases. Patient and tumor characteristics were retrieved from the Danish Breast Cancer Cooperative Group database. Immunohistochemical analyses of TIMP-1 and Ki67 and measurements of HER2 on formalin-fixed paraffin-embedded tumor tissue were performed. No significant differences in the immunoreactivity of TIMP-1 and Ki67 were found between patients with and without NSN metastases. Six of seven HER2 positive patients did not have NSN metastases, but the results did not reach statistical significance. Despite being prognostic markers in breast cancer, TIMP-1 and Ki67 could not predict NSN metastases in women with micrometastatic disease to SN. Larger studies are needed to further validate HER2 as a marker for NSN metastases in these patients. PMID- 22085361 TI - Antimicrobial susceptibility to parenteral and oral agents in a largely polyclonal collection of CTX-M-14 and CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae. AB - Activity of oral and parenteral antimicrobials against consecutively isolated extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (n = 149) and Klebsiella pneumoniae (n = 20) was determined, and susceptibility test methods were compared for parenteral beta-lactams. Polymerase chain reaction (PCR) targeting bla(CTX-M), bla(SHV) and bla(TEM), and DNA sequencing and epidemiological typing with pulsed-field gel electrophoresis were performed. PCR targeting pabB was screened for E. coli O25b-ST131. Minimum inhibitory concentrations (MICs) were determined using Etest and broth microdilution. Disc diffusion was performed according to European Committee on Antimicrobial Susceptibility Testing (EUCAST). Dominating genotypes were bla(CTX-M-15) (75%) and bla(CTX-M-14) (23%). Four E. coli clusters (7-18 isolates) were found. Forty two per cent of E. coli belonged to O25b-ST131. Ciprofloxacin resistance was 72%, trimethoprim resistance was 70%. Among E. coli, resistance to mecillinam (13%), nitrofurantoin (7%) and fosfomycin (3%) was low, although resistance was high in K. pneumoniae (25%, 60%, 85%). Susceptibility to ertapenem was 99%, piperacillin tazobactam 91%, tigecycline 96% and temocillin 76%. Susceptibility rates obtained with broth microdilution and Etest were in agreement for cefotaxime (2 vs 1%) and ceftazidime (9 vs 11%), but not for piperacillin-tazobactam (59 vs 91%). With disc diffusion major errors occurred with piperacillin-tazobactam (18/169). Several therapeutic alternatives exist for ESBL-producing E. coli, but few exist for K. pneumoniae. Disc diffusion and Etest can accurately predict susceptibility to cefotaxime and ceftazidime, but not to piperacillin-tazobactam with the present breakpoints. PMID- 22085362 TI - Gonococcal infection in symptomatic and asymptomatic persons seeking medical clinics in Sofia--a 3-year study 2008-2010. AB - The aim was to determine the prevalence of gonococcal infection and to compare the results with those received by other researchers, because in Bulgaria a good medical practice for the laboratory confirmation, report and therapy is lacking. A total of 617 specimens from symptomatic and asymptomatic persons attending clinics in Sofia from January 2008 to December 2010 were tested by culture and in house PCR. Using PCR Neisseria gonorrhoeae was identified in six urethral (6.25%) and eight (1.54%) cervical specimens. By applying culture method, N. gonorrhoeae positive result was found in 12 swabs--one cervical and one urethral swab less. The positive results correspond predominantly to persons with genital complains and suspicions for gonococcal or other sexually transmitted infection. This is the first study in Bulgaria since 1989 and determines the prevalence of N. gonorrhoeae to 2.3% over a 3-year period. Detection by culture was slightly less sensitive than by nucleic acid amplification test (NAAT). Continuous monitoring of gonorrhea by culture and NAAT is important for public health in Bulgaria. PMID- 22085363 TI - A mathematical approach to the optimal examination of lymph nodes. AB - There is no scientific evidence to support the idea that serial sectioning along the short axis of the lymph node is superior to a single bisection along the long axis. We mathematically evaluated methods of lymph node dissection and applied the result to six lymph nodes that had produced false negative results at the time of frozen examination. We simplified the geometry of a lymph node to that of a three-dimensional ellipse and compared two different cutting methods. Let A be the cross-sectional area obtained through a single bisection along the long axis, and let B be the sum of the cross-sectional areas of n fragments obtained via serial cutting along the short axis. The smallest n (n*) that makes a B larger than A can be calculated. n* = [3L + ?9L2 + 16S2)/4S]. ([alpha], the smallest integer greater than or equal to alpha; L, long axis; S, short axis). The probabilities of tumor detection when the node is bisected along the long axis (P(D(A)|E)) and when serially cut along the short axis (P(D(B)|E)) are as follows. P(D(A)|E = {(3/2)S2 - 3ST + T2}T/(S - T)3. and P(D(B)|E) = (n - 1){(1 + 1/n)L2 - 3LT + T2}T/(L - T)3. (T, size of the tumor cell cluster). According to these formulas, three out of six lymph nodes were not examined in the most appropriate manner. PMID- 22085364 TI - The use of a porcine intestinal cell model system for evaluating the food safety risk of Bacillus cereus probiotics and the implications for assessing enterotoxigenicity. AB - The use of porcine intestinal cell lines in assessing toxicity of Bacillus cereus probiotics in conjunction with animal challenge trials with toxigenic B. cereus was investigated. Toxigenic and toxin deletion mutants of B. cereus and two probiotic strains (Paciflor and Toyocerin) were examined for bacterial attachment, cytotoxicity and ability to induce nitric oxide as markers of toxicity. Both cytotoxicity and production of nitric oxide were detected in wild type toxigenic strains and the Paciflor probiotic strain but not Toyocerin. Attachment of B. cereus was low (less than 1%) in all strains. Discrimination between toxigenic B. cereus and the probiotic strains was possible semi quantitatively via dilution. Despite cytotoxicity in vitro, challenge experiments using 10(8)-10(9) spores of the toxigenic B. cereus NVH75/95 in weaned piglets did not induce diarrhoea or intestinal lesions. Thus, the pig small intestinal epithelial intestinal cell line PSI is appropriate for identification of potential toxicity in B. cereus strains and sets a low threshold for risk of enterotoxicity to humans. PMID- 22085365 TI - Characterization of SCCmec elements in methicillin-resistant Staphylococcus epidermidis isolated from blood cultures from neonates during three decades. AB - Staphylococcus epidermidis is a major cause of nosocomial infections in immunocompromised patients and the predominant pathogen in catheter-related infections and bloodstream infections. Approximately 70-80% of S. epidermidis carry the mecA gene encoding methicillin resistance. The mecA gene is located on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec). The aim of this study was to characterize the SCCmec elements as well as the adjacent arginine catabolic mobile element (ACME) in 30 clinical blood isolates of mecA positive S. epidermidis obtained from neonates and collected over a period of three decades. The ccr and mec gene complexes were identified using PCR. The SCCmec elements were found among 29/30 isolates and 13 different combinations of ccr gene complexes and mec gene complexes were identified. Staphylococcus epidermidis regularly carried multiple copies of ccr gene complexes, but only one class of mec gene complex. Three isolates could be assigned the SCCmec type III (3A). The combinations of ccr gene complexes and the mec gene complexes differed among the three decades. The most frequent combination was class B mec in combination with ccr1 and ccr2. Staphylococcus epidermidis may constitute a large reservoir for SCCmec elements, and frequent exchange of mobile genetic elements between staphylococcal species may explain the emergence of new MRSA strains. PMID- 22085366 TI - Immunoglobulin G antibodies against deamidated-gliadin-peptides outperform anti endomysium and tissue transglutaminase antibodies in children <2 years age. AB - To investigate the usefulness of deamidated-gliadin-peptides-antibodies in the diagnosis of celiac disease, serology was tested in 212 children suspected with celiac disease who had undergone a small-intestinal-biopsy. For deamidated gliadin-peptides-antibodies, two kits were tested. Positive and negative predictive values for IgA deamidated-gliadin-peptides-antibodies using the Bindazyme-kit were 89% and 74%, while the Quanta-Lite-kit had values of 89% and 85%, respectively. For the IgG subtype using the Bindazyme-kit, these values were 85% and 89%, while they were 85% and 91% for the Quanta-Lite-kit. The positive predictive values for endomysium and tissue-transglutaminase antibodies were disappointing (77% and 87%), although the negative predictive values were better (97% and 96%). When the analysis was restricted to the 41 children aged <2 years, no misclassifications occurred with IgG deamidated-gliadin-peptides-antibodies giving 100% accuracy in both kits. The positive predictive value reached 100% for tissue-transglutaminase antibodies and both kits for IgA deamidated-gliadin peptides-antibodies, while the negative predictive value was 94% in these assays. Positive and negative predictive values for endomysium antibodies were 96% and 93%, respectively. In conclusion, although deamidated-gliadin-peptides-antibodies do not outperform anti-endomysium antibodies in the total study population, the IgG subtype seems to be the best test in children aged <2 years, reaching 100% accuracy. PMID- 22085367 TI - Isolation of Brevibacillus brevis from tracheal aspirates of a hospitalized patient. PMID- 22085369 TI - Reflections on sex research among young Bedouin in Jordan: risks and limitations. AB - Research about sexuality is characterised by silences and invisibilities. This is particularly evident in some Islamic Arab societies where discussion of sexuality in general is not encouraged and practices such as homosexuality or pre-marital sex are not acknowledged. This creates a barrier to carrying out sex research and also means that much of the research-based knowledge and methodologies developed in a Western setting may have limited applicability. This paper uses research recently carried out among Bedouin young women in Jordan to examine these limitations and the extent to which research approaches and findings from relatively liberal Western cultures are appropriate and relevant. Following a description of the cultural context in which the study took place, the paper identifies potential risks of conducting sex research in this setting and the research limitations related to this risk. Finally, it addresses the question of whether doing sex research has any value given these restrictions. PMID- 22085368 TI - General strategy to analyse coat colour phenotypes in mice. PMID- 22085370 TI - The impact of late diagnosis on the survival of patients following their first AIDS-related hospitalization in Belo Horizonte, Brazil. AB - The purpose of this study is to estimate the survival probability of patients following their first admission for the treatment of AIDS to an infectious disease reference hospital in Belo Horizonte, Brazil, during 2005. Study subjects were monitored during a 12-month period to identify factors associated with survival probability. Late diagnosis was recorded among many of the 250 study subjects: almost half (44.8%) were diagnosed less than 30 days prior to or during their hospitalization. A high mortality rate was also detected: 39.6% of the subjects died during the 12 months of monitoring. The cumulative survival probability of the cohort group was estimated at 68.0% after 3 months and at 61.2% after 12 months. However, certain patient subgroups analyzed had even lower cumulative survival probabilities after 12 months of monitoring: if diagnosed during hospitalization, it was estimated at only 48.0% and those with no record of antiretroviral treatment had a 48.5% cumulative survival probability. Patients with severe anemia had the lowest survival probability, similar among the two lymphocyte count groups (<1000 mm(3) and >=1000 mm(3)), the former with a 45.5% survival probability and the latter with a 46.7% one. The proportional death risk was 2.5-fold higher for men residing in other area than the capital city of the State of Minas Gerais and greater metropolitan region when compared with women residing there. The findings of this study highlight the importance of early diagnosis for predicting patient survival and reinforce the necessity of facilitating HIV diagnosis. PMID- 22085371 TI - A combined approach in characterization of an effective w/o hand cream: the influence of emollient on textural, sensorial and in vivo skin performance. AB - To formulate a consumer-acceptable cosmetic product, numerous demands have to be fulfilled, and as the most important, efficacy (both real and perceived), adequate aesthetic (visual perception) and all sensorial characteristics have to be achieved. In this study, four model water-in-oil creams intended for hand care, varying in one emollient component, were submitted to rheological, sensory and textural characterization, and their efficacy was evaluated in in vivo study on human volunteers. Our results indicate that certain alteration restricted to the oil phase induced a change in all investigated characteristics, showing that each instrumental measurement can be used as a sensitive tool in the characterization of cream samples. Regarding the correlation between physical measurements and certain sensory attributes, it is possible to formulate a product with specific sensory characteristics by using pre-defined rheological or textural parameters. To obtain a complete sensory profile of a cosmetic product, a detailed sensory evaluation should be carried out according to the existing standard practices, which are both time- and money-consuming. However, a modified sensory study could be useful for fast in-line screening along with instrumental characterization of a novel cosmetic emulsion product and could be particularly helpful in the process of distinguishing a single formulation from several differing in one component. PMID- 22085372 TI - The chloroplast ATP-dependent Clp protease in vascular plants - new dimensions and future challenges. AB - The ATP-dependent Clp protease is by far the most intricate protease in chloroplasts of vascular plants. Structurally, it is particularly complex with a proteolytic core complex containing 11 distinct subunits along with three potential chaperone partners. The Clp protease is also essential for chloroplast development and overall plant viability. Over the past decade, many of the important characteristics of this crucial protease have been revealed in the model plant species Arabidopsis thaliana. Despite this, challenges still remain in fully resolving certain key features, in particular, how the assembly of this multisubunit protease is regulated, the full range of native protein substrates and how they are targeted for degradation and how this complicated enzyme might have developed from simpler bacterial forms. This article focuses upon the recent advances in revealing the details underlying these important features. It also take the opportunity to speculate upon many of these findings in the hope of stimulating further investigation. PMID- 22085373 TI - Diagnosis and treatment of low-back pain because of paraspinous muscle spasm: a physician roundtable. AB - BACKGROUND: Despite the availability of evidence-based guidelines to diagnose and treat acute low-back pain, practical application is nonuniform and physician uncertainty regarding best practices is widespread. OBJECTIVE: The objective of this study was to further optimal treatment choices for screening, diagnosing, and treating acute low-back pain caused by paraspinous muscle spasm. METHODS: Four experts in pain medicine (three family physicians and one physiatrist) participated in a roundtable conference call on October 18, 2010, to examine current common practices and guidelines for diagnosing and treating acute low back pain and to offer commentary and examples from their clinical experience. RESULTS: Participants discussed the preferred choices and timing of diagnostic and imaging tests, nonpharmacologic therapies, nonopioid and opioid medication use, biopsychosocial evaluation, complementary therapies, and other issues related to treatment of acute low-back pain. Principal clinical recommendations to emerge included thorough physical exam and medical history, early patient mobilization, conservative use of imaging tests, early administration of muscle relaxants combined with nonsteroidal anti-inflammatory medications to reduce pain and spasm, and a strong emphasis on patient education and physician-patient communication. CONCLUSIONS: Early, active management of acute low-back symptoms during the initial onset may lead to better patient outcomes, reducing related pain and disability and, possibly, preventing progression to chronicity. PMID- 22085374 TI - Cardiovascular support in preterm infants: a survey of practices in Australia and New Zealand. AB - AIM: Management of haemodynamic instability in premature neonates and selection of inotropic therapy are protocol driven, and therapeutic choices lack scientific validation. The aim of this study was to characterise practices related to the management of haemodynamic instability in premature infants. METHODS: An electronic web-based questionnaire was emailed to all neonatologists and advanced trainees in Australia and New Zealand. Respondents were presented with a series of questions related to the management of hypotension in a 1-day-old, extremely low birthweight infant, and opinions were collected. RESULTS: Survey response rate was 65% (114/176). Haemodynamically significant ductus arteriosus, systemic blood flow and left ventricular afterload were considered the most important physiologic concepts by 81, 68 and 50%, respectively. After initial crystalloid replacement, the next step in management reported included a second bolus (35%), dobutamine (28%), dopamine (17%) or clinician-performed cardiac ultrasound (CPCU) (20%). In the setting of hypotension resistant to dobutamine and dopamine, the most common strategies were to perform CPCU (57%), or administer hydrocortisone (39%), epinephrine (3.5%) or milrinone (<1%). The majority (66%) of respondents felt that premature infants are over-treated on the basis of presumed hypotension, while 83% felt that performing a CPCU would enhance clinical decision-making. CONCLUSIONS: Wide variation in the approach to management of haemodynamic instability in extremely low birthweight infants was identified. Haemodynamic information provided by a CPCU was considered highly desirable by the majority of the respondents. PMID- 22085376 TI - Hepatocellular carcinoma treated with sorafenib. PMID- 22085375 TI - Long-term follow-up of phase II trial of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer. AB - BACKGROUND: Chemoradiation improves survival for patients with locally advanced non-small cell lung cancer (NSCLC), but clinical outcomes beyond five years are rarely reported. The aim of the present study was to identify the long-term results of a phase II study of docetaxel and cisplatin with concurrent thoracic radiation. METHODS: We previously reported short-term outcomes from the phase II study, which enrolled 42 patients (aged <= 75 years) with unresectable stage III NSCLC. We continued to follow these patients for long-term clinical outcomes. RESULTS: At a median follow-up for all patients of 6.3 years (range: 5.2-7.1 years), the median survival time was 2.1 years and the actual five-year survival rate was 31%. Among 14 patients who were progression-free longer than two years, three patients died due to bacterial or fungal pneumonia and one died due to gall bladder cancer. CONCLUSIONS: Thirty-one percent of locally advanced patients having NSCLC treated with docetaxel and cisplatin and concurrent thoracic radiation survived beyond five years. Progression-free patients might be cautiously followed up taking precautions against emerging pneumonia. PMID- 22085378 TI - Aspirin use and development of inflammatory bowel disease: confounding or causation? PMID- 22085379 TI - Aspirin use and development of inflammatory bowel disease: confounding or causation? authors' reply. PMID- 22085381 TI - Intracervical procedures and the risk of subsequent very preterm birth: a case control study. AB - OBJECTIVE: To investigate the relation of prior intracervical procedures with very preterm birth. DESIGN: A population-based case-control study. SETTING: The study was conducted in Australia between 2002 and 2004. SAMPLE: Three hundred and forty-five women having a medically indicated and 236 having a spontaneous singleton birth between 20 and 31 weeks of gestation and 796 women selected randomly from all those giving birth at >=37 weeks of gestation. METHODS: Interview data were analysed using logistic regression. MAIN OUTCOME MEASURE: Very preterm birth. RESULTS: Very preterm birth was significantly associated with having any intracervical procedure [adjusted odds ratio (AOR) 2.07; 95% confidence interval (CI) 1.6-2.7], in particular curettage associated with abortion (AOR 1.80; 95% CI 1.2-2.6). Assisted reproductive technology procedures were significantly associated with medically indicated very preterm birth (AOR 3.07; 95% CI 1.8-5.3) and treatments for precancerous cervical changes were significantly associated with spontaneous very preterm birth, as follows: conization/cone biopsy (AOR 3.33; 95% CI 1.8-6.2) and cauterization/ablation (AOR 2.27; 95% CI 1.4-3.8). Suction aspiration for abortion, abnormal Pap smear without treatment and abortion without instrumentation were not associated with very preterm birth. CONCLUSIONS: Intracervical procedures are associated with very preterm birth. Notably, curettage rather than any other procedure associated with abortion appears to be implicated in the risk. The introduction of infection during cervical procedures may be the common link with risks found. Changing clinical practice in the management of abortion and human papillomavirus vaccination may lead to lowering the risks of very preterm birth. PMID- 22085380 TI - Drug discovery research targeting the CXC chemokine receptor 4 (CXCR4). PMID- 22085382 TI - Role of genotyping in non-small cell lung cancer treatment: current status. AB - Non-small cell lung cancer (NSCLC) is a common malignant disease with an extremely poor prognosis. Chemotherapeutic treatment for advanced disease is currently based on histological subtyping, but recent discoveries of genetic alterations in subsets of NSCLC have already changed clinical practice with regard to Egfr mutations as predictive markers of response to gefitinib and erlotinib. This has also paved the way for the integration of molecular analyses into early phase clinical trials, as demonstrated by the clinical development of crizotinib, effective in lung cancer harbouring Alk rearrangements. Similarly, other subgroups of NSCLC carry potentially targetable molecular alterations and their study has the potential to change the diagnostic and therapeutic approach to lung cancer in the near future. In contrast to a wealth of knowledge surrounding genomic alterations in lung adenocarcinomas, fewer data are available concerning squamous cell lung cancer (SCC), although recent data demonstrate that genotyping can provide new therapeutic perspectives in SCC treatment. Moreover, the study of molecular predictive markers of response to chemotherapy aims to improve chemotherapeutic treatment, increasing efficacy and limiting toxicity. PMID- 22085383 TI - Serotonergic anti-obesity agents: past experience and future prospects. AB - The role of serotonin (5-hydroxytryptamine) in appetite control is long established. Serotonergic manipulations reduce food intake in rodents in a manner consistent with satiety. In humans, drugs such as fenfluramine, dexfenfluramine and sibutramine all reduce energy intake, suppress hunger and enhance satiety. Effects on eating behaviour and subjective sensations of appetite are associated with the weight loss-inducing effects of these treatments. Currently, no appetite suppressing drugs are approved specifically for the treatment of obesity. However, a new generation of serotonergic drugs have progressed through clinical development. The serotonin 5-HT(2C)-receptor selective agonist lorcaserin, a drug specifically developed to target satiety without producing the side effect profiles of its predecessors, has been shown to significantly reduce energy intake and body weight. The weight loss produced by lorcaserin appears modest, and behavioural effects, particularly its supposed satiety-enhancing effects, have yet to be characterized. The monoaminergic re-uptake inhibitor tesofensine has also been shown to produce impressive weight loss in smaller-scale clinical studies. It remains unclear if this drug produces any effects on appetite mediated by serotonin, or whether weight loss is produced largely through enhanced energy expenditure. Evidence indicates that tesofensine strengthens satiety, but behavioural specificity and psychological side effects remain an issue. The serotonergic system remains a viable target for anti-obesity treatment. In this review, we examine the limited behavioural data available on these two new CNS-acting appetite suppressants. PMID- 22085384 TI - Adjuvant therapy for early colon cancer: current status. AB - Adjuvant chemotherapy after resection of the primary tumour reduces the risk of death by an absolute 5% in UICC (Union Internationale Contre le Cancer) stage II colon cancer and about 15-20% in stage III. Adjuvant treatment has to be evaluated separately for each stage due to the different clinical situations: in stage II about 80% of patients are cured by surgery alone, whereas only about half of patients with stage III are cured by surgery. Decisions on adjuvant treatment need to be discussed with the patient on an individual basis, and take into account patient characteristics (performance status, age, co-morbidity and patient preference) as well as cancer features (pathological stage, grading and overall risk of relapse). Recently, capecitabine in combination with oxaliplatin has been approved for treatment of stage III colon cancer, providing the benefits of an oral fluoropyrimidine. Predictive markers for guidance of treatment have gained importance, particularly in stage II disease. Microsatellite instability, a well known prognostic factor, might be predictive for a lack of activity of fluorouracil treatment in some stage II patients. Furthermore, patients aged >=70 years do not seem to obtain the same benefit from combination therapy compared with those aged <70 years. The impact of these current developments on daily clinical practice is discussed in this review. PMID- 22085386 TI - Single-pill telmisartan and amlodipine: a rational combination for the treatment of hypertension. AB - Despite the well documented benefits conferred by adequate control of hypertension, the majority of hypertensive patients display suboptimal control and few patients achieve blood pressure (BP) levels <140/90 mmHg. As a consequence, combination therapy will be required in the majority of patients to achieve target BP. Fixed-dose combinations of antihypertensives not only simplify treatment regimens, contributing to enhanced patient adherence, they provide superior BP-lowering efficacy and an improved tolerability profile. Fixed-dose combinations have become the strategy of choice in high-risk patients or those with stage 2-3 hypertension. The combination of a renin-angiotensin system inhibitor (RASI) with a calcium channel blocker (CCB) is a first-line combination that, in addition to its antihypertensive efficacy, reduces oedema, the main adverse effect of the dihydropyridine CCB and the main factor limiting their use. In morbidity/mortality studies, this fixed-dose combination has also demonstrated superiority over a RASI combined with a diuretic. The single-pill combination of telmisartan and amlodipine has been shown to produce a dose-dependent BP-lowering effect significantly greater than that of either agent administered as monotherapy. These findings have been confirmed by ambulatory BP monitoring in patients with stage 1 and 2 hypertension, which demonstrated that single-pill telmisartan/amlodipine provides substantial 24-hour BP-lowering efficacy. A higher proportion of patients achieved 24-hour BP goals of <130/80 mm Hg on combination therapy. The superior efficacy of combination therapy has been demonstrated across a broad range of patients, including those with moderate-to severe hypertension, diabetes mellitus and obesity. Moreover, combined use of telmisartan and amlodipine reduces the incidence of amlodipine-induced oedema, making it a preferred combination for the treatment of hypertension. PMID- 22085385 TI - Pharmacological considerations for the proper clinical use of aminoglycosides. AB - Aminoglycosides constitute one of the oldest classes of antimicrobials. Despite their toxicity, mainly nephrotoxicity and ototoxicity, aminoglycosides are valuable in current clinical practice, since they retain good activity against multidrug-resistant Gram-negative pathogens, such as Pseudomonas aeruginosa and Acinetobacter spp. Time-kill studies have shown a concentration-dependent and partially concentration-dependent bacterial killing against Gram-negative and Gram-positive bacteria, respectively. Pharmacodynamic data gathered over recent decades show that the administration of aminoglycosides by an extended-interval dosing scheme takes advantage of the maximum potential of these agents, with the goal of achieving an area under the concentration-time curve (AUC) of 100 mg . h/L over 24 hours and a peak plasma drug concentration (C(max)) to minimum inhibitory concentration (MIC) ratio of 8-10. Several clinical conditions that are common in seriously ill patients result in expansion of the extracellular space and can lead to a lower than desirable C(max) with the usual loading dose. Extended-interval dosing schemes allow adequate time to decrease bacterial adaptive resistance, a phenomenon characterized by slow concentration-independent killing. Adaptive resistance is minimized by the complete clearance of the drug before the subsequent dose, thus favouring the extended-interval dosing schemes. The efficacy of these schemes is also safeguarded by the observed post-antibiotic sub-MIC effect and post-antibiotic leukocyte enhancement, which inhibit bacterial regrowth when the serum aminoglycoside levels fall below the MIC of the pathogen. In everyday clinical practice, aminoglycosides are usually used empirically to treat severe sepsis and septic shock while awaiting the results of antimicrobial susceptibility testing. The European Committee on Antimicrobial Susceptibility Testing acknowledges the regimen-dependent nature of clinical breakpoints for aminoglycosides, i.e. of MIC values that classify bacterial isolates into sensitive or resistant, and bases its recommendations on extended-interval dosing. To a large extent, the lack of correlation between in vitro antimicrobial susceptibility testing and clinical outcome is derived from the fact that the available clinical breakpoints for aminoglycosides are set based on mean pharmacokinetic parameters obtained in healthy volunteers and not sick patients. The nephrotoxicity associated with once- versus multiple-daily administration of aminoglycosides has been assessed in numerous prospective randomized trials and by several meta-analyses. The once-daily dosing schedule provides a longer time of administration until the threshold for nephrotoxicity is met. Regarding ototoxicity, no dosing regimen appears to be less ototoxic than another. Inactivation of aminoglycosides inside the bacterial pathogens occurs by diverse modifying enzymes and by operation of multidrug efflux systems, making both of these potential targets for inhibition. In summary, despite their use for several decades, the ideal method of administration and the preferred dosing schemes of aminoglycosides for most of their therapeutic indications need further refinement. Individualized pharmacodynamic monitoring has the potential of minimizing the toxicity and the clinical failures of these agents in critically ill patients. PMID- 22085387 TI - Current status of targeted therapies for mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL) with treatment outcomes that have historically been poorer than those observed with other NHL subtypes. Patients typically present with advanced-stage disease and frequent extranodal involvement; the median age at diagnosis is >60 years. Recent improvements in progression-free and overall survival have been observed with more dose-intensive strategies, although at least half of patients diagnosed with MCL are not eligible for such treatment approaches based on age and co morbidities. In addition, therapy options for relapsed MCL are limited. Only bortezomib is approved for treatment of relapsed MCL in the US. Development of targeted therapy approaches to minimize toxicities while preserving anti neoplastic properties is of particular importance in MCL. Multiple ongoing studies are attempting to build on the known efficacy of bortezomib by evaluating combination regimens with other targeted agents or cytotoxic chemotherapy. The mammalian target of rapamycin (mTOR) inhibitor temsirolimus has known activity in MCL, making this an attractive class of agents for further investigation in combination regimens. Rituximab and other monoclonal antibodies are being evaluated for novel roles in MCL treatment, including as maintenance therapy. Other classes of drugs being investigated in MCL are immunomodulatory agents, inhibitors of the phosphoinositide 3-kinase/Akt and B-cell receptor signalling pathways, and inhibitors of bcl-2 and histone deacetylase. Although many of the agents appear to have modest single-agent activity, the favourable toxicity profile of many agents will make them best suited for incorporation into combination regimens. PMID- 22085388 TI - Eculizumab: a review of its use in paroxysmal nocturnal haemoglobinuria. AB - Eculizumab is a humanized monoclonal antibody indicated for the treatment of paroxysmal nocturnal haemoglobinuria (PNH). It binds specifically and with high affinity to the complement protein C5, thereby preventing the formation of the terminal complement complex C5b-9, which mediates cell lysis. In patients with PNH, eculizumab inhibits terminal complement mediated intravascular haemolysis. In clinical trials of PNH patients, eculizumab reduced intravascular haemolysis compared with baseline and placebo, as determined by significantly decreased lactate dehydrogenase (LDH) levels. Significant reductions in LDH levels were achieved within the first week of treatment, with near normal levels achieved at week 2 and maintained throughout longer term treatment, including periods of up to 36 months. Eculizumab achieved rapid and sustained efficacy, regardless of baseline LDH levels or platelet counts. In adults with PNH, eculizumab treatment for 26 weeks achieved stabilization of haemoglobin levels in significantly more patients than placebo treatment, and reduced the requirement for packed red cell transfusions to a significantly greater extent than placebo. Half of all patients in the eculizumab group became transfusion independent compared with no patients in the placebo group. Eculizumab was also associated with significant improvements in fatigue and health-related quality-of-life scores in several trials. Over the long term, the survival of PNH patients treated with eculizumab was normalized. Eculizumab was generally well tolerated in clinical trials of PNH patients, including treatment periods of up to 5.5 years. The risk of Neisseria meningitidis is increased with eculizumab and patients must be vaccinated prior to treatment and monitored throughout. Thus, eculizumab, the first targeted terminal complement inhibitor, provides an effective and generally well tolerated treatment for PNH patients, who have previously been without adequate treatment options. PMID- 22085390 TI - Low-dose topiramate plus sodium divalproate for positive responders intolerant to full-dose monotherapy. AB - BACKGROUND: Neuromodulators such as topiramate (TPM) and divalproex sodium (DVS) are effective in the preventive treatment of migraine. Nonetheless, patients often discontinue their use due to side effects. OBJECTIVES: The study aims to determine whether the combination of lower doses of TPM and DVS may be useful for patients responsive to higher doses of the individual drugs but experiencing intolerable side effects. METHODS: This clinic-based study was conducted to evaluate a series of patients who experienced at least a 50% reduction in headache frequency after 6 weeks of treatment with either TPM 100 mg/day or DVS 750 mg/day, but suffered intolerable drug-related side effects. At that point, patients were switched to TPM (50 mg in the morning and 25 mg at night) plus DVS 500 mg/day (single dose) and reevaluated after 6 further weeks. RESULTS: Thirty eight patients were evaluated. Mean age was 37 years, and 84% were female. Of the 38, 17 (77.3%) initially were using TPM only, and 10 (62.5%) initially were using DVS only. After 6 weeks on combination therapy, 27 (62.9%) reported improved tolerability without any decrease in efficacy. Five patients who initially were using TPM only and six using DVS only failed to return for follow-up or were noncompliant with treatment due to persistent or worsening side effects. CONCLUSIONS: This small, open-label study suggests that the combination of TPM and DVS in doses lower than those typically used for migraine prophylaxis may be an effective option for patients who benefited from higher doses of these same medications used as monotherapy but were unable to tolerate such treatment due to side effects. PMID- 22085389 TI - Liraglutide: a review of its use in the management of type 2 diabetes mellitus. AB - Liraglutide (Victoza(r)) is a subcutaneously administered glucagon-like peptide-1 (GLP-1) receptor agonist produced by recombinant DNA technology and used as an adjunct to diet and exercise in the treatment of adults with type 2 diabetes mellitus. This article reviews the clinical efficacy and tolerability of liraglutide in adults with type 2 diabetes, and provides a summary of its pharmacological properties. Recently published pharmacoeconomic studies of liraglutide are also reviewed. Administered subcutaneously, liraglutide (usually 1.2 or 1.8 mg once daily) generally produced greater improvements in glycaemic control than active comparators or placebo when administered as monotherapy or in combination with one or two oral antidiabetic drugs (OADs) to adults with type 2 diabetes in numerous randomized, controlled phase III trials. These included six trials in the LEAD trial programme that was designed to evaluate the efficacy and safety of liraglutide across a continuum of antihyperglycaemic management for patients with type 2 diabetes. Liraglutide was generally well tolerated, with a low risk of hypoglycaemia evident, in the phase III trials. The most common adverse events were gastrointestinal and included nausea and diarrhoea; most events were mild to moderate in severity and decreased in incidence over time. In conclusion, liraglutide has an important place in the management of adults with type 2 diabetes across a continuum of care. As well as providing effective glycaemic control, liraglutide improves pancreatic beta-cell function and leads to bodyweight loss, thereby addressing some of the unmet needs of patients treated with traditional OADs. PMID- 22085391 TI - Topical pimecrolimus effect on Fas inducing apoptosis in oral lichen planus: a clinical immunohistochemical study. AB - OBJECTIVE: To investigate the effectiveness of pimecrolimus treatment in patients not responding to corticosteroid treatment and to investigate its effect on Fas expression on keratinocytes in oral lichen planus (OLP). SUBJECTS AND METHODS: Twenty patients with OLP were recruited from the Oral Medicine Clinic at the School of Dentistry, Ain Shams University, Egypt. Pimecrolimus 1% cream with a hydrophilic adhesive gel base was applied to the oral lesions, four times daily, for a total of 2 months. A marker lesion was identified and assessed by clinical scoring (CS). The symptomatology score was obtained using a visual analog scale (VAS). Pre-treatment and post-treatment specimens were immunohistochemically stained for detecting Fas. RESULTS: The results of clinical scores showed statistically high significant improvement (P = 0.0001). The mean VAS decreased significantly over time as well as the mean of Fas expression (P < 0.05). The overall percentage of reduction from baseline to week 8 was 87%, 93%, and 67% for clinical scores, visual analog score, and Fas expression, respectively. CONCLUSIONS: Topical pimecrolimus reduced Fas expression, and it appears to be a promising alternative treatment for OLP. PMID- 22085393 TI - The role of distress in uptake and response to predisposition genetic testing: the BMPR2 experience. AB - This study examines psychological determinants and effects of participating in genetic testing among persons diagnosed with or at risk for developing primary pulmonary arterial hypertension. Longitudinal data were drawn from orally administered surveys with 70 affected or at-risk individuals concerning their thoughts, feelings, and decision making about testing for mutations in BMPR2. Distress was measured by use of the Impact of Events Scale. Variations in tolerance for ambiguity were also examined. Although uptake of testing was low, as is common for incompletely penetrant mutations that lack clear therapeutic interventions, we found that those who participated in testing evidenced greater reduction in distress compared to those who had not participated in testing, irrespective of test result. No differences in tolerance for ambiguity by testing status were found. Participation in genetic testing, irrespective of test results, may be particularly beneficial to individuals who may have genetic mutations and who are experiencing high levels of distress. PMID- 22085394 TI - Parenting through genetic uncertainty: themes in the disclosure of breast cancer risk information to children. AB - AIM: Among mothers undergoing BRCA1/2 testing and their spouses/partners, this study sought to examine decision support needs and motivations for family communication of genetic risk information to asymptomatic children. METHODS: This study gathered data from 213 tested mothers and 104 of their untested parenting partners 1 month after maternal receipt of genetic test results and upon making a decision about communicating genetic information to their child (ages 8-21 years). Data include parents' perceived needs for family communication decision support, decision motivations, and parent-child communication. RESULTS: Parents reported high decision support needs (e.g., educational materials, professional counseling, peer assistance). Motivations for disclosure to children among mothers and partners focused on promoting the parent-child bond and maintaining family health (55.3% and 75%, respectively) and promoting positive child affect (44.7% and 25.5%, respectively). Motivations for nondisclosure to children among mothers and partners focused on the lack of appropriateness (69.6% and 51.3%, respectively) and relative importance of genetic test results (30.4% and 48.7%, respectively). Significant discrepancies in parental motivation for family communication were observed. Decision support needs were highest among disclosing mothers with affect-related motivations [t (129)=2.47; p=0.01]. Parent-child communication was poorest among nondisclosing mothers concerned about the appropriateness of genetic information for their child [t (77)=-3.29; p=.002]. CONCLUSIONS: Parents receiving information about hereditary cancer predisposition have unmet needs when making decisions about disclosing genetic risk information to their asymptomatic children. These data can guide the development of cancer risk communication decision support interventions for parents undergoing such testing. PMID- 22085395 TI - Serum neural cell adhesion molecule is hyposialylated in hereditary inclusion body myopathy. AB - Hereditary inclusion body myopathy (HIBM) is a young-adult onset autosomal recessive disorder caused by a hypomorphic rate limiting enzyme of sialic acid biosynthesis. The enzyme is UDP-N-acetylglucosamine 2-epimerase/N acetylmannosamine kinase, and is encoded by the GNE gene. HIBM causes slowly progressive muscle weakness and atrophy. Patients are typically diagnosed at 20 30 years of age, and most patients are incapacitated and wheelchair-confined by 30-50 years of age. Some sialic acid containing glycoproteins, including neural cell adhesion molecule (NCAM), are hyposialylated in HIBM muscle biopsy samples. We developed a method to allow detection of serum NCAM sialylation using Western blot, and tested serum samples from several patients and a HIBM mouse model. Preliminary results showed a clear difference in polysialylated and hyposialylated forms of NCAM extracted from serum, and showed NCAM is hyposialylated in HIBM serum samples. This initial finding may prove useful in reducing the need for serial muscle biopsies in HIBM treatment trials. Additional studies are underway to further validate this finding and to evaluate the specificity, reliability, and robustness of this potential serum biomarker for HIBM. PMID- 22085396 TI - Machismo, public health and sexuality-related stigma in Cartagena. AB - This paper reports on an ethnographic study in Cartagena, Colombia. Over a seven month fieldwork period, 35 men and 35 women between 15 and 60 years of age discussed the social context of HIV/AIDS through in-depth interviews, life histories and drawing. Participants considered the transgression of traditional gender roles as prescribed by machismo a major risk factor for HIV infection. In addition, they integrated public-health concepts of risk groups with these long standing constructions of gender roles and sexuality-related stigma to create the notion of 'AIDS carriers'. The bricolage between machismo, public health and sexuality-related stigma that participants created and consequent preventive measures (based on an avoidance of sex with people identified as 'AIDS carriers') was a dynamic process in which participants were aware that changes in this particular interpretation of risk were necessary to confront the local epidemic. PMID- 22085397 TI - Haemodialysis nurses knowledge about methicillin-resistant Staphylococcus aureus. AB - Healthcare workers may lack knowledge about antibiotic-resistant bacteria and thereby increase the spread of such organisms. The aim of the present study was to describe the relationship between self-rated knowledge and actual knowledge about methicillin-resistant Staphylococcus aureus (MRSA) among 326 Swedish haemodialysis nurses. Data were collected through a postal questionnaire. The findings suggest that ongoing education about MRSA should be provided to haemodialysis nurses, but also that standardised evaluation of adequate knowledge, skills and competencies' regarding safe practices is warranted. Future research should focus on effective mechanisms to ensure that haemodialysis nurses provide safe MRSA care. PMID- 22085398 TI - Anti-melanoma, tyrosinase inhibitory and anti-microbial activities of gold nanoparticles synthesized from aqueous leaf extracts of Teraxacum officinale. AB - There has been a tenacious search for pharmaceuticals of natural origin, as they are cost-effective and are noted for having little or no side effects. The rate at which diseases are developing resistance to synthetic drugs is quite alarming, and the side effects of these drugs remain an excruciating agony to the pharmaceutical industry. Gold nanoparticles (AuNPs) have wide applications in current technology. However, their use in medicine has not been adequately explored. Chemical methods for the synthesis are associated with environmental benignity and tissue toxicity on in vivo administration. For the first time, we have synthesized AuNPs from leaf extracts of Teraxacum officinale that were found to have significant anti-melanoma, tyrosinase inhibitory and anti-microbial effects, and hence stand as promising candidates for use in cosmetics medical and food industries. PMID- 22085399 TI - Proteolytic system of plant mitochondria. AB - The existence of a proteolytic system which can specifically recognize and cleave proteins in mitochondria is now well established. The components of this system comprise processing peptidases, ATP-dependent peptidases and oligopeptidases. A short overview of experimentally confirmed proteases mainly from Arabidopsis thaliana is provided. The role of the mitochondrial peptidases in plant growth and development is emphasized. We also discuss the possibility of existence of as yet unidentified plant homologs of yeast mitochondrial ATP-independent proteases. PMID- 22085400 TI - Synthesis and metal-catalyzed reactions of gem-dihalovinyl systems. PMID- 22085401 TI - Orbital Rosai-Dorfman disease with subperiosteal bone involvement mimicking eosinophilic granuloma. AB - The presentation of RDD as an anterior subperiosteal orbital mass with bone involvement has, to the authors' knowledge, not been previously reported. We describe a case of Rosai-Dorfman disease (RDD) presenting as an anterior superolateral subperiosteal orbital mass with erosion of overlying bone mimicking eosinophilic granuloma. It was debulked using endoscopic-guided curettage and the patient was given both local and systemic corticosteroids. Careful histological analysis revealed the diagnosis of RDD and the patient remains asymptomatic and recurrence free at 16 months follow-up. Involvement of the pituitary gland, a recognized yet unusual finding in this condition was also noted. RDD should be considered in the differential diagnosis of a soft tissue mass of the superolateral orbit. PMID- 22085402 TI - Generation of dyspeptic symptoms by direct acid and water infusion into the stomachs of functional dyspepsia patients and healthy subjects. AB - BACKGROUND: The mechanisms of the development of symptoms in functional dyspepsia (FD) patients have not been fully elucidated. We previously reported that acid directly infused into the stomach causes dyspeptic symptoms in asymptomatic healthy controls (HCs); however, the response to acid infusion of FD patients was not determined. AIM: To investigate the severity of dyspeptic symptoms induced by direct acid infusion in FD subjects and HCs. METHODS: This was a multi-centre, cross-over, randomised, double-blind study in 23 FD subjects and 32 HCs. FD was defined using the Rome III criteria. All subjects were Helicobacter pylori negative. Each subject received two tests; 0.1 mol/L hydrochloric acid and water infused into the stomach. The presence and severity of 12 dyspeptic symptoms were assessed using a visual analogue scale. RESULTS: The proportion of subjects developing symptoms by acid or water infusion was significantly greater in FD subjects than HCs. All of the FD subjects experienced at least one symptom by water or acid infusion. In the FD subjects, the severity of symptoms was significantly greater with acid infusion than water infusion. The severity of symptoms in total and the scores for eight of the 12 symptoms induced by acid infusion was significantly greater in FD subjects than in HCs. CONCLUSIONS: The severity of dyspeptic symptom generation induced by direct acid infusion into the stomach was significantly greater in functional dyspepsia subjects than in healthy controls, suggesting that hypersensitivity to acid is one of the important mechanisms of the development of symptoms in functional dyspepsia patients. PMID- 22085403 TI - Fear of childbirth; the relation to anxiety and depression. AB - OBJECTIVE: To study the associations of anxiety and depression with fear of childbirth. DESIGN: A cross-sectional questionnaire study. SETTING: Prenatal public healthcare in Norway. SAMPLE: Pregnant women (n=1642) recruited during November 2008 until April 2010. METHODS: Data were collected by a postal questionnaire at pregnancy week 32. Fear of childbirth was measured by the Wijma Delivery Expectancy Questionnaire (W-DEQ) and by a numeric rating scale. Symptoms of anxiety were measured by the Hopkins Symptom Check List (SCL-25) and symptoms of depression by the Edinburgh Postnatal Depression Scale (EPDS). MAIN OUTCOME MEASURE: Fear of childbirth. RESULTS: Eight per cent (137 of 1642) of the women had fear of childbirth (W-DEQ>=85), 8.8% (145 of 1642) had anxiety (SCL anxiety>=18) and 8.9% (146 of 1642) had depression (EPDS>=12). More than half (56.2%) of the women with fear of childbirth did not have anxiety or depression; however, presence of anxiety or depression increased the prevalence of fear of childbirth (odds ratio 2.4, 95% confidence interval 1.1-5.2 and odds ratio 8.4, 95% confidence interval 4.8-14.7, respectively). Women with both anxiety and depression had the highest prevalence of fear of childbirth (odds ratio 11.0, 95% confidence interval 6.6-18.3). Similar associations of anxiety and depression were estimated by using the numerical rating scale for measuring fear of childbirth. CONCLUSIONS: Presence of anxiety and depression increased the prevalence of fear of childbirth; however, the majority of women with fear of childbirth had neither anxiety nor depression. PMID- 22085404 TI - Cytokine expression during early and late phase of acute Puumala hantavirus infection. AB - BACKGROUND: Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. RESULTS: We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha and TGF-beta1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-beta1 and TNF-alpha in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-alpha significantly decreased whereas TGF-beta1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-alpha but low immunosuppressive TGF-beta1 levels and vice versa . CONCLUSION: High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-beta1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection. PMID- 22085405 TI - Inhibition of glutathione S-transferase M1 by new gabosine analogues is essential for overcoming cisplatin resistance in lung cancer cells. AB - A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene. PMID- 22085406 TI - A proteomic approach to analyzing responses of Arabidopsis thaliana root cells to different gravitational conditions using an agravitropic mutant, pin2 and its wild type. AB - BACKGROUND: Root gravitropsim has been proposed to require the coordinated, redistribution of the plant signaling molecule auxin within the root meristem, but the underlying molecular mechanisms are still unknown. PIN proteins are membrane transporters that mediate the efflux of auxin from cells. The PIN2 is important for the basipetal transport of auxin in roots and plays a critical role in the transmission of gravity signals perceived in the root cap to the root elongation zone. The loss of function pin2 mutant exhibits a gravity-insensitive root growth phenotype. By comparing the proteomes of wild type and the pin2 mutant root tips under different gravitational conditions, we hope to identify proteins involved in the gravity-related signal transduction. RESULTS: To identify novel proteins involved in the gravity signal transduction pathway we have carried out a comparative proteomic analysis of Arabidopsis pin2 mutant and wild type (WT) roots subjected to different gravitational conditions. These conditions included horizontal (H) and vertical (V) clinorotation, hypergravity (G) and the stationary control (S). Analysis of silver-stained two-dimensional SDS-PAGE gels revealed 28 protein spots that showed significant expression changes in altered gravity (H or G) compared to control roots (V and S). Whereas the majority of these proteins exhibited similar expression patterns in WT and pin2 roots, a significant number displayed different patterns of response between WT and pin2 roots. The latter group included 11 protein spots in the H samples and two protein spots in the G samples that exhibited an altered expression exclusively in WT but not in pin2 roots. One of these proteins was identified as annexin2, which was induced in the root cap columella cells under altered gravitational conditions. CONCLUSIONS: The most interesting observation in this study is that distinctly different patterns of protein expression were found in WT and pin2 mutant roots subjected to altered gravity conditions. The data also demonstrate that PIN2 mutation not only affects the basipetal transport of auxin to the elongation zone, but also results in an altered expression of proteins in the root columella. PMID- 22085407 TI - Validation of metabolic syndrome using medical records in the SUN cohort. AB - BACKGROUND: The objective of this study was to evaluate the validity of self reported criteria of Metabolic Syndrome (MS) in the SUN (Seguimiento Universidad de Navarra) cohort using their medical records as the gold standard. METHODS: We selected 336 participants and we obtained MS related data according to Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF). Then we compared information on the self reported diagnosis of MS and MS diagnosed in their medical records. We calculated the proportion of confirmed MS, the proportion of confirmed non-MS and the intraclass correlation coefficients for each component of the MS. RESULTS: From those 336 selected participants, we obtained sufficient data in 172 participants to confirm or reject MS using ATP III criteria. The proportion of confirmed MS was 91.2% (95% CI: 80.7- 97.1) and the proportion of confirmed non-MS was 92.2% (95% CI: 85.7-96.4) using ATP III criteria. The proportion of confirmed MS using IDF criteria was 100% (95% CI: 87.2-100) and the proportion of confirmed non-MS was 97.1% (95% CI: 85.1-99.9). Kappa Index was 0.82 in the group diagnosed by ATP III criteria and 0.97 in the group diagnosed by IDF criteria. Intraclass correlation coefficients for the different component of MS were: 0.93 (IC 95%:0.91- 0.95) for BMI; 0.96 (IC 95%: 0.93-0.98) for waist circumference; 0.75 (IC 95%: 0.66-0.82) for fasting glucose; 0.50 (IC 95%:0.35-0.639) for HDL cholesterol; 0.78 (IC 95%: 0.70-0.84) for triglycerides; 0.49 (IC 95%:0.34-0.61) for systolic blood pressure and 0.55 (IC 95%: 0.41-0.65) for diastolic blood pressure. CONCLUSIONS: Self-reported MS based on self reported components of the SM in a Spanish cohort of university graduates was sufficiently valid as to be used in epidemiological studies. PMID- 22085409 TI - Management of sulfur mustard-induced chronic pruritus: a review of clinical trials. AB - Skin is among the most heavily damaged organs upon sulfur mustard (SM) exposure. Chronic complications due to SM-induced dermatotoxicity are quite frequent among intoxicated patients. Nevertheless, the exact pathophysiology of SM-induced chronic cutaneous complications has not been well clarified yet. The present review highlights clinically important findings on the management of SM-induced chronic skin complications with a particular focus on pruritus as the most prevalent symptom that has a significant impact on patients' quality of life. Some methodological pitfalls that implicate the validity of the trials have also been identified. PMID- 22085408 TI - Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study. AB - INTRODUCTION: Soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a biologic marker of fibrinolysis and inflammation. The aim of this study was to investigate the diagnostic and prognostic value of systemic and pulmonary levels of suPAR in burn patients with inhalation trauma who need mechanical ventilation. METHODS: suPAR was measured in plasma and nondirected lung-lavage fluid of mechanically ventilated burn patients with inhalation trauma. The samples were obtained on the day of inhalation trauma and on alternate days thereafter until patients were completely weaned from the mechanical ventilator. Mechanically ventilated patients without burns and without pulmonary disease served as controls. RESULTS: Systemic levels of suPAR in burn patients with inhalation trauma were not different from those in control patients. On admission and follow up, pulmonary levels of suPAR in patients with inhalation trauma were significantly higher compared with controls. Pulmonary levels of suPAR highly correlated with pulmonary levels of interleukin 6, a marker of inflammation, and thrombin-antithrombin complexes, markers of coagulation, but not plasminogen activator activity, a marker of fibrinolysis. Systemic levels of suPAR were predictive of the duration of mechanical ventilation and length of intensive care unit (ICU) stay. Duration of mechanical ventilation and length of ICU stay were significantly longer in burn-injury patients with systemic suPAR levels > 9.5 ng/ml. CONCLUSIONS: Pulmonary levels of suPAR are elevated in burn patients with inhalation trauma, and they correlate with pulmonary inflammation and coagulation. Although pulmonary levels of suPAR may have diagnostic value in burn-injury patients, systemic levels of suPAR have prognostic value. PMID- 22085410 TI - Novel pathway of centrosome amplification that does not require DNA lesions. AB - Centrosome amplification (also known as centrosome overduplication) is common in cancer cells and can be induced by DNA damaging agents. However, the mechanism and significance of centrosome amplification during carcinogenesis or after DNA damage are not clear. Previously, we showed that centrosome amplification could be induced by 3-aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) polymerases (PARPs) in mouse embryonic fibroblasts. In this paper, we determined if the effect of 3-AB on centrosome amplification was dependent on DNA damage in CHO-K1 cells. We used the well-known mutagen/carcinogen N-methyl-N'-nitro-N nitrosoguanidine (MNNG). Ten micromolar MNNG and 10 mM 3-AB induced significant centrosome amplification in 18.1 +/- 1.1% and 19.4 +/- 1.8% of CHO-K1 cells, respectively, compared to 7.0 +/- 0.5% of untreated CHO-K1 cells. AG14361, another potent inhibitor of PARPs, also induced centrosome amplification. We then used gamma-H2AX analysis and alkaline comet assays to show that 10 MUM MNNG induced a significant number of DNA lesions and cell cycle arrest at the G(2) /M phase. However, 10 mM 3-AB neither induced DNA lesions nor altered cell cycle progression. In the umu test, 10 MUM MNNG was mutagenic, but 10 mM 3-AB was not. In addition, 10 MUM MNNG induced significant accumulation of ataxia telangiectasia mutated protein in the nuclei, but 10 mM 3-AB did not. Thus, we found no association between apparent DNA lesions and centrosome amplification after 3-AB treatment. Therefore, we propose the presence of a novel pathway for centrosome amplification that does not necessarily require DNA lesions but involves regulation of epigenetic changes or post-translational modifications including polyADP-ribosylation. PMID- 22085411 TI - Photoregulation of cytochrome P450 activity by using caged compound. AB - Cytochrome P450 (P450) species play an important role in the metabolism of xenobiotics, and assaying the activities of P450 is important for evaluating the toxicity of chemicals in drugs and food. However, the lag time caused by the introduction and mixing of sample solutions can become sources of error as the throughput is heightened by increasing the sample number and decreasing the sample volume. To amend this technological obstacle, we developed a methodology to photoregulate the activity of P450 by using photoprotected (caged) compounds. We synthesized caged molecules of nicotinamide adenine dinucleotide phosphate (NADP(+)) and glucose 6-phosphate (G6P), which are involved in the generation of NADPH (cofactor of P450). The use of caged-G6P completely blocked the P450 catalysis before the UV illumination, whereas caged-NADP(+) resulted in a little background reaction. Upon UV illumination, more than 90% of the enzymatic activity could be restored. The use of caged-G6P enabled assays in isolated microchambers (width, 50 MUm; height, 50 MUm) by encapsulating necessary ingredients in advance and initiating the reaction by UV illumination. The initiation of enzymatic reaction could be observed in a single microchamber. Minimizing uncertainties caused by the introduction and mixing of solutions led to significantly reduced errors of obtained kinetic constants. PMID- 22085412 TI - Oral neurovascular hamartoma: a lesion searching for a name. AB - BACKGROUND: Neurovascular hamartoma (NVH), in particular in the oral cavity, is rarely described in the literature. The low number of cases may reflect a genuine rarity of the lesion, or it may be due to its being unrecognized and/or under reported. OBJECTIVES: To investigate clinical and microscopic features of oral NVH and to define microscopic diagnostic criteria with emphasis on the differential diagnosis. METHODS: Archival cases diagnosed as oral NVH between 1999 and 2011 were retrieved; clinical and demographic data were collected, and a paired morphometric analysis was conducted, with each case of NVH a case of fibrous hyperplasia (FH) from the same oral location. The nerve bundle and blood vessel density were quantified in five microscopic fields at *100 magnification. RESULTS: The study group included 25 oral NVH, 11 men and 14 women, aged 6-76 years, (mean 44). The majority occurred in the tongue (54%), followed by the buccal mucosa and lower lip (17% each), clinically presenting as asymptomatic 0.25-2.5 cm exophytic masses. Microscopic characteristics included poorly circumscribed masses of closely packed nerve bundles and blood vessels in a loose matrix, containing minimal or no inflammation. The mean nerve bundle density was significantly higher in NVH (4.28 +/- 1.26) in comparison with FH (0.27 +/- 0.27), (P < 0.00001), and mean vessel density was significantly lower (5.98 +/- 1.4 vs. 7.8 +/- 1.9, respectively), (P < 0.0003). CONCLUSION: Oral NVH may not be as rare as previously considered. Morphometric analysis demonstrated that NVH presents a separate distinct entity. PMID- 22085413 TI - FOCUSED CLINICAL CAMPAIGN IMPROVES MINERAL AND BONE DISORDER OUTCOMES. AB - As with other disease states, mineral and bone disorder (MBD) management is challenging and may benefit from more systematic management. To evaluate the effectiveness of a focused campaign to improve MBD outcomes, we compared the percentage of patients meeting 2003 Kidney Dialysis Outcomes Quality Initiative (KDOQI)-recommended MBD targets between baseline and 18 months after programme initiation. The four components of the clinical campaign were: (1) a set of grids allowing simultaneous evaluation of MBD test results, (2) a weighted, facility level cumulative scoring system representing percent of patients within KDOQI recommended MBD targets, (3) team involvement and (4) patient education. Eighteen months after programme initiation, the percent of patients simultaneously meeting all 2003 KDOQI targets increased 7% and the percent meeting calcium and phosphorus targets increased 24% and 8%, respectively. These findings suggest that a coordinated clinical campaign with effective tools, outcome tracking and sharing and team involvement is an effective strategy to improve MBD outcomes. PMID- 22085414 TI - Association of claw disorders with claw horn colour in Norwegian red cattle--a cross-sectional study of 2607 cows from 112 herds. AB - Claw disorders cause problems in dairy cattle all over the world. Nutrition, feeding, environment, claw trimming routines, hormonal changes related to calving and genetics are among the factors which influence the pathogenesis. The colour of the claw horn (pigmentation) has been suggested to play a role. The aim of this study was to investigate if there were any associations between the colour of the sole horn and claw disorders detected at claw trimming. Altogether, 2607 cows on 112 farms were claw trimmed once and the colour (dark, mixed or light) of the right lateral hind claw and hind claw disorders were recorded by 13 trained claw trimmers. The data were analysed using logistic regression models with logit link function, binomial distribution and herd and claw trimmer as repeated effects, with herd nested within claw trimmer. Haemorrhages of the sole (HS) and white line (HWL) were more frequently found in light than in dark claws (OR = 2.61 and 2.34, respectively). Both HS (OR = 1.43) and corkscrewed claws (OR = 1.84) were slightly more prevalent among cows which had claws with mixed colour versus dark claws. There were no significant associations of other claw disorders with claw horn colour. PMID- 22085415 TI - Comparison of body mass index and triceps skinfold at 5 years and young adult body mass index, waist circumference and blood pressure. AB - AIM: To examine which measure of obesity at 5 years, body mass index (BMI) or triceps skinfold thickness, is most strongly associated with 21-year risk factors for cardiovascular disease (CVD), including BMI, waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP). METHODS: Longitudinal birth cohort study with BMI and triceps skinfold measurements at age 5, and BMI, WC and blood pressure at 21 years. Overweight and obesity at 5 years were determined according to Cole-International Obesity Task Force standards, at 21, by World Health Organization definitions. Triceps skinfold thickness measurements were converted to a z-score, and cut-offs for overweight and obesity were chosen to reflect similar proportions to the BMI subgroups. BMI, WC, SBP and DBP were also measured at 21 years. RESULTS: Five-year BMI and triceps skinfold thickness were both significantly associated with the CVD risk measures at 21 years. For overweight/obesity at 5 years, the adjusted odds ratio (95% confidence interval) for 21-year overweight/obesity was 5.6 (4.2, 7.4), for 21-year WC was 1.5 (1.2, 2.0). Mean difference (95% CI) in BMI was 4.4 (3.9, 5.0), in WC 8.3 cm (6.8, 9.8), in SBP 2.4 mm Hg (0.5, 4.3), in DBP 1.1 mm Hg (0.1, 2.2). For skinfold, the similar findings were odds ratio 2.6 (2.0, 3.4) and 1.2 (0.9, 1.6) for 21-year BMI and WC, and mean differences of 2.6 (2.0, 3.2), WC 4.8 cm (3.3, 6.3), SBP 2.3 mm Hg (0.5, 4.2) and DBP 0.7 mm Hg (-0.4, 1.8). CONCLUSIONS: In children with overweight/obesity, BMI rather than triceps skinfold is the preferred epidemiological measure for identifying young adult CVD risk markers of BMI, WC and blood pressure. PMID- 22085417 TI - Timing of screening for gestational diabetes mellitus in women with moderate and severe obesity. AB - OBJECTIVE: We evaluated screening with a diagnostic oral glucose tolerance test earlier than 20 weeks gestation in women with moderate to severe obesity. DESIGN: Prospective observational study. SETTING: Large university teaching hospital. POPULATION: We enrolled 100 women booking for antenatal care in the first trimester at their convenience. METHODS: Height and weight were measured and body mass index calculated. Only women with a body mass index > 34.9 kg/m(2) were included. Women were booked for a 100 g oral glucose tolerance test before 20 weeks and, if normal, another test at 28 weeks gestation. MAIN OUTCOME MEASURES: Impaired glucose tolerance and gestational diabetes mellitus. RESULTS: Of the 100 women given an appointment for an oral glucose tolerance test before 20 weeks gestation, 92 attended. Of these, 10 (10.8%) women had an abnormal result, with impaired glucose tolerance in five (5.4%) cases and gestational diabetes mellitus in five (5.4%) cases. Of those with a normal result at 20 weeks, 81 attended for a repeat test at 28 weeks gestation. A further four (4.9%) had impaired glucose tolerance and four (4.9%) had gestational diabetes mellitus. A total of 18 (20.5%) of the 88 women who complied with screening had an abnormal test. CONCLUSIONS: Women who have moderate/severe obesity have a one in five chance of having an abnormal diagnostic oral glucose tolerance test when screened for gestational diabetes mellitus. To optimize maternal glycemic control in pregnancy, we suggest that women with a body mass index > 34.9 kg/m(2) may need to be screened early in pregnancy and, if the test is normal, again at 28 weeks gestation. PMID- 22085416 TI - End-of-life decision-making in Canada: the report by the Royal Society of Canada expert panel on end-of-life decision-making. AB - This report on end-of-life decision-making in Canada was produced by an international expert panel and commissioned by the Royal Society of Canada. It consists of five chapters. Chapter 1 reviews what is known about end-of-life care and opinions about assisted dying in Canada. Chapter 2 reviews the legal status quo in Canada with regard to various forms of assisted death. Chapter 3 reviews ethical issues pertaining to assisted death. The analysis is grounded in core values central to Canada's constitutional order. Chapter 4 reviews the experiences had in a number of jurisdictions that have decriminalized or recently reviewed assisted dying in some shape or form. Chapter 5 provides recommendations with regard to the provision of palliative care in Canada, as well as recommendations for reform with respect to the various forms of assisted death covered in this document. PMID- 22085418 TI - ent-Kaurane diterpenoids from Croton tonkinensis stimulate osteoblast differentiation. AB - Four new ent-kaurane diterpenoids (1-4) were isolated from the leaves of Croton tonkinensis by bioactivity-guided fractionation using an in vitro osteoblast differentiation assay. Their structures were identified as ent-11beta-acetoxykaur 16-en-18-ol (1), ent-11alpha-hydroxy-18-acetoxykaur-16-ene (2), ent-14beta hydroxy-18-acetoxykaur-16-ene (3), and ent-7alpha-hydroxy-18-acetoxykaur-16-ene (4). Compounds 1-4 significantly increased alkaline phosphatase activity and osteoblastic gene promoter activity. Compounds 1-3 also increased the levels of ALP and collagen type I alpha mRNA in C2C12 cells in a dose-dependent manner. These results suggest that ent-kaurane diterpenoids from C. tonkinensis have a direct stimulatory effect on osteoblast differentiation and may be potential therapeutic molecules against bone diseases such as osteoporosis. PMID- 22085419 TI - The bacteriophage WORiC is the active phage element in wRi of Drosophila simulans and represents a conserved class of WO phages. AB - BACKGROUND: The alphaproteobacterium Wolbachia pipientis, the most common endosymbiont in eukaryotes, is found predominantly in insects including many Drosophila species. Although Wolbachia is primarily vertically transmitted, analysis of its genome provides evidence for frequent horizontal transfer, extensive recombination and numerous mobile genetic elements. The genome sequence of Wolbachia in Drosophila simulans Riverside (wRi) is available along with the integrated bacteriophages, enabling a detailed examination of phage genes and the role of these genes in the biology of Wolbachia and its host organisms. Wolbachia is widely known for its ability to modify the reproductive patterns of insects. One particular modification, cytoplasmic incompatibility, has previously been shown to be dependent on Wolbachia density and inversely related to the titer of lytic phage. The wRi genome has four phage regions, two WORiBs, one WORiA and one WORiC. RESULTS: In this study specific primers were designed to distinguish between these four prophage types in wRi, and quantitative PCR was used to measure the titer of bacteriophages in testes, ovaries, embryos and adult flies. In all tissues tested, WORiA and WORiB were not found to be present in excess of their integrated prophages; WORiC, however, was found to be present extrachromosomally. WORiC is undergoing extrachromosomal replication in wRi. The density of phage particles was found to be consistent in individual larvae in a laboratory population. The WORiC genome is organized in conserved blocks of genes and aligns most closely with other known lytic WO phages, WOVitA and WOCauB. CONCLUSIONS: The results presented here suggest that WORiC is the lytic form of WO in D. simulans, is undergoing extrachromosomal replication in wRi, and belongs to a conserved family of phages in Wolbachia. PMID- 22085420 TI - Parathyroid autotransplantation in extensive head and neck resections: case series report. AB - Permanent or temporary hypoparathyroidism may be a debilitating result of radical cervical surgery, as noted most commonly following thyroid or parathyroid surgery. However, it can also be the outcome of any surgical procedure involving bilateral extensive manipulation of the anterior neck triangle, especially in order to ensure oncologically adequate surgical margins. We report our experience of three patients that underwent parathyroid immediate autotransplanation following extensive surgical manipulations of the neck region for oncological reasons. PTH levels were restored to normal by the fourth postoperative week, allowing us to wean the patients off calcium and vitamin D3 supplementation, which was attributed to full autograft function. Parathyroid autotransplantation, immediate or delayed, is a simple and safe technique which should be considered by the surgeon whenever there is a high risk for postoperative hypoparathyroidism following radical operations of the neck for oncological reasons. PMID- 22085421 TI - Healthy babies through infant-centered feeding protocol: an intervention targeting early childhood obesity in vulnerable populations. AB - BACKGROUND: Poor feeding practices during infancy contribute to obesity risk. As infants transition from human milk and/or formula-based diets to solid foods, these practices interfere with infant feeding self-regulation and healthy growth patterns. Compared with other socioeconomic groups, lower-income mothers are more likely to experience difficulty feeding their infants. This may include misinterpreting feeding cues and using less-than-optimal feeding styles and practices, such as pressuring infants during mealtimes and prematurely introducing solid food and sweetened beverages. The Healthy Babies trial aims to determine the efficacy of a community-based randomized controlled trial of an in home intervention with economically and educationally disadvantaged mother-infant dyads. The educational intervention is being conducted during the infant's first 6 months of life to promote healthy transition to solids during their first year and is based on the theory of planned behavior. METHODS/DESIGN: We will describe our study protocol for a multisite randomized control trial being conducted in Colorado and Michigan with an anticipated sample of 372 economically and educationally disadvantaged African American, Hispanic, and Caucasian mothers with infants. Participants are being recruited by county community agency staff. Participants are randomly assigned to the intervention or the control group. The intervention consists of six in-home visits by a trained paraprofessional instructor followed by three reinforcement telephone contacts when the baby is 6, 8, and 10 months old. Main maternal outcomes include a) maternal responsiveness, b) feeding style, and c) feeding practices. Main infant outcome is infant growth pattern. All measures occur at baseline and when the infant is 6 and 12 months old. DISCUSSION: If this project is successful, the expected outcomes will address whether the home-based early nutrition education intervention is effective in helping mothers develop healthy infant feeding practices that contribute to improving infant health and development and reducing the risk of early-onset childhood obesity. TRIAL REGISTRATION: Current Controlled Trials ACTRN126100000415000. PMID- 22085422 TI - Association between public views of mental illness and self-stigma among individuals with mental illness in 14 European countries. AB - BACKGROUND: Little is known about how the views of the public are related to self stigma among people with mental health problems. Despite increasing activity aimed at reducing mental illness stigma, there is little evidence to guide and inform specific anti-stigma campaign development and messages to be used in mass campaigns. A better understanding of the association between public knowledge, attitudes and behaviours and the internalization of stigma among people with mental health problems is needed. METHOD: This study links two large, international datasets to explore the association between public stigma in 14 European countries (Eurobarometer survey) and individual reports of self-stigma, perceived discrimination and empowerment among persons with mental illness (n=1835) residing in those countries [the Global Alliance of Mental Illness Advocacy Networks (GAMIAN) study]. RESULTS: Individuals with mental illness living in countries with less stigmatizing attitudes, higher rates of help seeking and treatment utilization and better perceived access to information had lower rates of self-stigma and perceived discrimination and those living in countries where the public felt more comfortable talking to people with mental illness had less self-stigma and felt more empowered. CONCLUSIONS: Targeting the general public through mass anti-stigma interventions may lead to a virtuous cycle by disrupting the negative feedback engendered by public stigma, thereby reducing self-stigma among people with mental health problems. A combined approach involving knowledge, attitudes and behaviour is needed; mass interventions that facilitate disclosure and positive social contact may be the most effective. Improving availability of information about mental health issues and facilitating access to care and help-seeking also show promise with regard to stigma. PMID- 22085423 TI - Epigenomic insights into common disease. AB - A report on the Wellcome Trust Scientific Conference 'Epigenomics of Common Diseases', Hinxton, Cambridge, UK, September 13-16, 2011. PMID- 22085424 TI - Comparative reactivity of remnant-like lipoprotein particles (RLP) and low density lipoprotein (LDL) to LDL receptor and VLDL receptor: effect of a high dose statin on VLDL receptor expression. AB - BACKGROUND: Comparison of the reactivity of remnant-like lipoprotein particles (RLP) and LDL particles to LDL receptor and VLDL receptor has not been investigated. METHODS: LDL receptor- or VLDL receptor-transfected ldlA-7, HepG2 and L6 cells were used. Human LDL and rabbit beta-VLDL were isolated by ultracentrifugation. Human RLP was isolated using an immunoaffinity mixed gel. The effect of statin on lipoprotein receptors was examined. RESULTS: Both LDL receptor and VLDL receptor recognized RLP. In LDL receptor transfectants, RLP, beta-VLDL and LDL all bound to LDL receptor. Cold RLP competed efficiently with DiI-beta-VLDL; however, cold LDL competed weakly. In VLDL receptor transfectants, RLP and beta-VLDL bound to VLDL receptor, but not LDL. RLP bound to VLDL receptor with higher affinity than beta-VLDL because of higher apolipoprotein E in RLP. LDL receptor expression was induced in HepG2 by the low concentration of statin while VLDL receptor expression was induced in L6 myoblasts at higher concentration. CONCLUSIONS: RLP are bound to hepatic LDL receptor more efficiently than LDL, which may explain the mechanism by which statins prevent cardiovascular risk by primarily reducing plasma RLP rather than by reducing LDL. Additionally, a high-dose of statins also may reduce plasma RLP through muscular VLDL receptor. PMID- 22085425 TI - Ethylene glycol poisoning: quintessential clinical toxicology; analytical conundrum. AB - Ethylene glycol poisoning is a medical emergency that presents challenges both for clinicians and clinical laboratories. Untreated, it may cause morbidly or death, but effective therapy is available, if administered timely. However, the diagnosis of ethylene glycol poisoning is not always straightforward. Thus, measurement of serum ethylene glycol, and ideally glycolic acid, its major toxic metabolite in serum, is definitive. Yet measurement of these structurally rather simple compounds is but simple. This review encompasses an assessment of analytical methods for the analytes relevant for the diagnosis and prognosis of ethylene glycol poisoning and of the role of the ethylene glycol metabolites, glycolic and oxalic acids, in its toxicity. PMID- 22085427 TI - Phase II multicenter, randomized, double-blind study of recombinant mutated human tumor necrosis factor-alpha in combination with chemotherapies in cancer patients. AB - We previously prepared a tumor necrosis factor (TNF)-alpha mutant (rmhTNF-alpha) that showed higher antitumor activity and lower systemic toxicity compared with native TNF-alpha. The safety profile and the pharmacokinetic characteristics of rmhTNF-alpha were suited for clinical use according to biological Investigational New Drug application, a standard guideline for new drug investigation in China. Here, we evaluate the activity and safety of rmhTNF-alpha combined with chemotherapies in head/neck, lung, colorectal, stomach, and renal cancer patients. Ninety-five eligible patients received i.m. rmhTNF-alpha treatment combined with standard chemotherapies. Another 95 patients were treated with standard chemotherapies. After two treatment cycles, one patient achieved a complete response and 24 patients had partial response, yielding an overall response rate (complete response + partial response) of 27.47% in the rmhTNF alpha plus chemotherapy cohort. The chemotherapy alone group acquired only a 11.39% response rate (P < 0.05). When compared between different cancers, a 48.89% response rate was detected in the 45 lung cancer patients of the combination cohort. The most common grade 1-2 adverse events of rmhTNF-alpha were drug-related fever, allergy, flu-like symptoms, and myalgia. No significant difference was found in grade 3-4 toxicities between the two cohorts. Based on the results of this research, rmhTNF-alpha can significantly enhance the effectiveness of chemotherapy. An extended phase III trial of rmhTNF-alpha combined with standard chemotherapy is warranted for evaluating its antitumor activity and toxicity in a larger cohort of tumor patients. The studies in this paper were registered with the State Food and Drug Administration of China (No. 2003S00692). PMID- 22085428 TI - Contacting versus insulated gate electrode for Si nanoribbon field-effect sensors operating in electrolyte. AB - Electric response to pH variations is employed to investigate Si nanoribbon field effect transistors (SiNRFETs) operating in electrolyte with different gate configurations. For devices with a conducting gate electrode for direct metal electrolyte contact, a well-defined electrode reaction leading to a stable electrode potential is essential for retaining a stable electrical potential of the electrolyte. However, noble metals such as Pt do not meet the stability requirement and consequently bring severe distortions to the electronic response. For devices with an insulated gate electrode relying on the principle of capacitive gate coupling, the capacitance between the gate electrode and the electrolyte should be made much larger than the gate capacitance established between the SiNR and the electrolyte. In this case, an efficient gate control as well as a high stability against external disturbances can be ensured. Further studies show that surface charging of the gate insulator is the main cause responsible for the pH response of the SiNRFETs. Hence, devices with different gate configurations give rise to a comparable pH sensitivity. PMID- 22085429 TI - Increasing the amphiphilicity of an estradiol based steroid structure by Barbier allylation--ring-closing metathesis--dihydroxylation sequence. AB - Polyhydroxylated steroids, such as brassinosteroids, phytoecdysteroids and steroid saponins, are structurally attractive compounds possessing a number of interesting biological properties. Accordingly, development of synthetic procedures to build steroid based structures mimicking the naturally occurring hydrophilic steroids is of topical interest. In the present work, a D-secoestrone derivative was modified further by Barbier-allylation - ring-closing metathesis - dihydroxylation sequence with the aim to prepare steroid based structures with limited hydrophilicity. A straightforward synthesis route was developed with the isolated yield for each step ranging from good to excellent. All compounds prepared were fully characterized by NMR spectroscopic techniques and completely assigned (1)H and (13)C spectra are reported herein. Finally, the effects of the synthesized amphiphilic steroid derivatives on the proliferation of cancer cells are reported and discussed. PMID- 22085430 TI - Identification of the needs of haemodialysis patients using the concept of Maslow's hierarchy of needs. AB - Along with basic survival and other clinical outcomes, patients' quality of life is an important indicator to reflect the needs of these patients. Human needs are classified in Maslow's hierarchy, where the most essential basic physiological need provides the base, and self actualisation is at the top of pyramid. AIM: The aim of this study is to identify the patients' needs who are on maintenance haemodialysis using concept of Maslow's hierarchy. METHOD: The descriptive study was conducted in the dialysis unit of Suez Canal University Hospitals. The study included 50 patients attending the dialysis unit. RESULTS: The findings showed that the patients' highest need was for self-esteem (92.0%), whereas the lowest was for love and belonging (38.0%). Statistically significant relationships were revealed between the identified love and belonging needs and patients' age and the duration of dialysis (p = 0.008). The total needs score was lower with the longer duration of dialysis (59.6 +/- 7.3), compared to those with a duration less than 24 months (65.7 +/- 8.1), p = 0.02. CONCLUSION: Based on the main study findings it is concluded that haemodialysis patients' highest need was for self esteem, and the lowest was for love and belonging. These needs increased with longer duration of dialysis. Nurses need to be aware of these findings in order to be able to supply the necessary support to help the patient regain his/her self-concept. PMID- 22085431 TI - Topiramate attenuates cerebral ischemia/reperfusion injury in gerbils via activating GABAergic signaling and inhibiting astrogliosis. AB - Impaired GABAergic inhibitory synaptic transmission plays an essential role in the pathogenesis of selective neuronal cell death following transient global ischemia. GABA(A) receptor (GABA(A)R), K+-Cl- co-transporter 2 (KCC2), Na+-K+-Cl- co-transporter 1 (NKCC1) and astrocytes are of particular importance to GABAergic transmission. The present study was designed to explore whether the neuroprotective effect of topiramate (TPM) was linked with the alterations of GABAergic signaling and astrocytes. The bilateral carotid arteries were occluded, and TPM (80 mg/kg/day (divided twice daily), i.p.) was injected into gerbils. At day 1, 3 and 7 post-ischemia, neurological deficit was scored and changes in hippocampal neuronal cell death were evaluated by Nissl staining. The apoptosis related regulatory proteins (procaspase-3, caspase-3, Bax and Bcl-2) and GABAergic signal molecules (GABA(A)R alpha1, GABA(A)R gamma2, KCC2 and NKCC1) were also detected using western blot assay. In addition, the fluorescent intensity and protein level of glial fibrillary acidic protein (GFAP), a major component of astrocyte, were examined by confocal and immunoblot analysis. Our results showed that TPM treatment significantly decreased neurological deficit scores, attenuated the ischemia-induced neuronal loss and remarkably decreased the expression levels of procaspase-3, caspase-3 as well as the ratio of Bax/Bcl 2. Besides, treatment with TPM also resulted in the increased protein expressions of GABA(A)R alpha1, GABA(A)R gamma2 and KCC2 together with the decreased protein level of NKCC1 in gerbils hippocampus. Furthermore, fluorescent intensity and protein level of GFAP were evidently reduced in TPM-treated gerbils. These findings suggest that the therapeutic effect of TPM on global ischemia/reperfusion injury appears to be associated with the enhancement of GABAergic signaling and the inhibition of astrogliosis in gerbils. PMID- 22085432 TI - Surface immobilization of bio-functionalized cubosomes: sensing of proteins by quartz crystal microbalance. AB - A strategy for tethering lipid liquid crystalline submicrometer particles (cubosomes) to a gold surface for the detection of proteins is reported. Time resolved quartz crystal microbalance (QCM-D) was used to monitor the cubosome protein interaction in real time. To achieve specific binding, cubosomes were prepared from the nonionic surfactant phytantriol, block-copolymer, Pluronic F 127, and a secondary biotinylated lipid, 1,2-distearoyl-sn-glycero-3 phosphoethanolamine-N-[biotinyl(polyethyleneglycol)-2000], which enabled attachment of the particles to a neutravidin (NAv)-alkanethiol monolayer at the gold surface of the QCM sensor chip. A second set of cubosomes was further functionalized with addition of the glycolipid (G(M1)) to facilitate a specific binding uptake of the protein, cholera toxin B subunit (CT(B)), from solution. QCM-D confirmed the specificity of the cubosome-NAv binding. The analysis of titration experiments, also performed with QCM, suggests that an optimal concentration of cubosomes is required for the efficient packing of the particles at the surface: high cubosome concentrations lead to chaotic cubosome binding onto the surface, sterically inhibiting surface attachment, or require significant reorganization to permit uniform cubosome coverage. The methodology enabled the straightforward preparation of a complex nanostructured edifice, which was then used to specifically capture analyte proteins (cholera toxin B subunit or free NAv) from solution, supporting the potential for development of this approach as a biosensing platform. PMID- 22085433 TI - Complications arising from a misdiagnosed giant lipoma of the hand and palm: a case report. AB - INTRODUCTION: Lipomas are benign tumors which may appear in almost any human organ. Their diagnosis rate in the hand region is not known. CASE PRESENTATION: We present the case of a 63-year-old Greek Caucasian woman with a giant lipoma of the hand and palm which was not initially diagnosed. After repeated surgical decompression of the carpal tunnel the patient was referred with persisting symptoms of median and ulnar nerve compression and a prominent mass of her left palm and thenar eminence. Clinical examination, magnetic resonance imaging, nerve conduction study and biopsy, revealed a giant lipoma in the deep palmar space (8.0 * 4.0 * 3.75 cm), which was also infiltrating the carpal tunnel. She had already undergone two operations for carpal tunnel syndrome with no relief of her symptoms and she also ended up with a severed flexor pollicis longus tendon. Definitive treatment was performed by marginal resection of the lipoma and restoration of the flexor pollicis longus with an intercalated graft harvested from the palmaris longus. Thirty months after surgery the patient had a fully functional hand without any neurological deficit. CONCLUSION: Not all lipomas of the wrist and hand are diagnosed. Our report tries to emphasize the hidden danger of lipomas in cases with carpal tunnel symptoms. The need for a high index of suspicion in conjunction with good clinical evaluation and the use of appropriate investigative studies is mandatory in order to avoid unnecessary operations and complications. Marginal excision of these tumors is restorative. PMID- 22085434 TI - Pseudomonas aeruginosa infections due to electronic faucets in a neonatal intensive care unit. AB - AIM: To evaluate the role of electronic faucets in a newborn intensive care unit during a Pseudomonas aeruginosa outbreak. METHODS: After three patients had P. aeruginosa bacteremia, environmental cultures including those from patient rooms, incubator, ventilators, total parenteral nutrition solutions, disinfection solutions, electronic and hand-operated faucet filters/water samples after removing filters and staff hands were taken. RESULTS: Only filters of electronic faucets and water samples after removing filters and one liquid hand soap showed P. aeruginosa (3-7 * 106 cfu/mL). We have removed the electronic faucets and new elbow-operated faucets were installed. Pulsed-field gel electrophoresis analysis of outbreak-blood culture isolates from two patients and isolates from electronic water faucets/one liquid hand soap indicated the presence of 90.7% genetically related subtype, probably from the same clone. Water cultures from new faucets were all clean after installation and after 7 months. CONCLUSION: We suggest that electronic faucets may be considered a potential risk for P. aeruginosa in hospitals, especially in high-risk units. PMID- 22085435 TI - Novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes. AB - With the aim of developing a novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes, various valsartan-loaded solid dispersions were prepared with water, hydroxypropyl methylcellulose (HPMC) and sodium lauryl sulphate (SLS). Effects of the weight ratios of SLS/HPMC and carrier/drug on both the aqueous solubility of valsartan and the drug-release profiles of solid dispersions were investigated. The physicochemical properties of solid dispersions were characterized using scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The bioavailability of the solid dispersions in rats was evaluated compared to valsartan powder and a commercial product (Diovan). Unlike the conventional solid dispersion system, the valsartan-loaded solid dispersion had a relatively rough surface and did not change the crystalline form of the drug. It was suggested that the solid dispersions were formed by attaching hydrophilic carriers to the surface of the drug, thus changing from a hydrophobic to a hydrophilic form without changing the crystalline form. The drug-loaded solid dispersion composed of valsartan/HPMC/SLS at a weight ratio of 3/1.5/0.75 improved the drug solubility by about 43-fold. It gave a higher AUC, C(max) and shorter T(max) compared to valsartan powder and the commercial product. The solid dispersion improved the bioavailability of the drug in rats by about 2.2 and 1.7-fold in comparison with valsartan powder and the commercial product, respectively. Thus, the valsartan-loaded solid dispersion would be useful for delivering poorly water soluble valsartan with enhanced bioavailability and no crystalline changes. PMID- 22085436 TI - Pre-, peri- and neonatal risk factors for autism. AB - OBJECTIVE: To identify pre-, peri- and neonatal risk factors for pervasive developmental disorders (PDD). METHODS: We searched the Medline database through March 2011 for relevant case-control and population-based studies on pre-, peri- and neonatal hazards related to PDD, including autism. We identified 85 studies for this review. Data were extracted systematically and organized according to risk factors related to family history, pregnancy, gestational age, delivery, birth milestones and the neonate's condition at birth. RESULTS: During the prenatal period, risk factors for PDD were advanced maternal or paternal ages, being firstborn vs. third or later, maternal prenatal medication use and mother's status as foreign born. During the perinatal and neonatal periods, the risk factors for PDD were preterm birth, breech presentation, planned cesarean section, low Apgar scores, hyperbilirubinemia, birth defect and a birthweight small for gestational age. The influence of maternal pre-eclampsia, diabetes, vomiting, infections and stress during pregnancy requires further study in order to determine risk for PDD. DISCUSSION: Despite evidence for the association of some pre-, peri- and neonatal risk factors associated with PDD, it remains unclear whether these risks are causal or play a secondary role in shaping clinical expression in individuals with genetic vulnerability. A plausible hypothsesis is that improvements in obstetric and neonatal management have led to an increased rate of survivors with pre-existing brain damage. Given the variety of risk factors, we propose that future studies should investigate combinations of multiple factors, rather than focusing on a single factor. PMID- 22085437 TI - Isolation and determination of the primary structure of a lectin protein from the serum of the American alligator (Alligator mississippiensis). AB - Mass spectrometry in conjunction with de novo sequencing was used to determine the amino acid sequence of a 35kDa lectin protein isolated from the serum of the American alligator that exhibits binding to mannose. The protein N-terminal sequence was determined using Edman degradation and enzymatic digestion with different proteases was used to generate peptide fragments for analysis by liquid chromatography tandem mass spectrometry (LC MS/MS). Separate analysis of the protein digests with multiple enzymes enhanced the protein sequence coverage. De novo sequencing was accomplished using MASCOT Distiller and PEAKS software and the sequences were searched against the NCBI database using MASCOT and BLAST to identify homologous peptides. MS analysis of the intact protein indicated that it is present primarily as monomer and dimer in vitro. The isolated 35kDa protein was ~98% sequenced and found to have 313 amino acids and nine cysteine residues and was identified as an alligator lectin. The alligator lectin sequence was aligned with other lectin sequences using DIALIGN and ClustalW software and was found to exhibit 58% and 59% similarity to both human and mouse intelectin-1. The alligator lectin exhibited strong binding affinities toward mannan and mannose as compared to other tested carbohydrates. PMID- 22085438 TI - An alternative physiological role for the EmhABC efflux pump in Pseudomonas fluorescens cLP6a. AB - BACKGROUND: Efflux pumps belonging to the resistance-nodulation-division (RND) superfamily in bacteria are involved in antibiotic resistance and solvent tolerance but have an unknown physiological role. EmhABC, a RND-type efflux pump in Pseudomonas fluorescens strain cLP6a, extrudes hydrophobic antibiotics, dyes and polycyclic aromatic hydrocarbons including phenanthrene. The effects of physico-chemical factors such as temperature or antibiotics on the activity and expression of EmhABC were determined in order to deduce its physiological role(s) in strain cLP6a in comparison to the emhB disruptant strain, cLP6a-1. RESULTS: Efflux assays conducted with (14)C-phenanthrene showed that EmhABC activity is affected by incubation temperature. Increased phenanthrene efflux was measured in cLP6a cells grown at 10 degrees C and decreased efflux was observed at 35 degrees C compared with cells grown at the optimum temperature of 28 degrees C. Membrane fatty acids in cLP6a cells were substantially altered by changes in growth temperature and in the presence of tetracycline. Changed membrane fatty acids and increased membrane permeability were associated with ~30-fold increased expression of emhABC in cLP6a cells grown at 35 degrees C, and with increased extracellular free fatty acids. Growth of P. fluorescens cLP6a at supra-optimal temperature was enhanced by the presence of EmhABC compared to strain cLP6a-1. CONCLUSIONS: Combined, these observations suggest that the EmhABC efflux pump may be involved in the management of membrane stress effects such as those due to unfavourable incubation temperatures. Efflux of fatty acids replaced as a result of membrane damage or phospholipid turnover may be the primary physiological role of the EmhABC efflux pump in P. fluorescens cLP6a. PMID- 22085439 TI - Efficacy and safety of inhaled formoterol 4.5 and 9 MUg twice daily in Japanese and European COPD patients: phase III study results. AB - BACKGROUND: This study evaluated the efficacy and safety of the long-acting beta2 agonist formoterol in patients with moderate-to-severe COPD. METHODS: This double blind, placebo-controlled, parallel-group, multinational phase III study randomized patients >= 40 years of age with moderate-to-severe COPD to inhaled formoterol 4.5 or 9 MUg twice daily (bid) via Turbuhaler or placebo for 12 weeks. Salbutamol 100 MUg/actuation via pMDI was permitted as reliever medication. The primary outcome variable was change (ratio) from baseline to treatment period in FEV1 60-min post-dose. RESULTS: 613 patients received treatment (formoterol 4.5 MUg n = 206; 9 MUg n = 199; placebo n = 208); 539 (87.9%) male; 324 (52.9%) Japanese and 289 (47.1%) European. End of study increases in FEV1 60-min post dose were significantly greater (p < 0.001 for both) with formoterol 4.5 and 9 MUg bid (113% of baseline for both) than with placebo, as were all secondary outcome measures. The proportion of patients with an improvement in St George's Respiratory Questionnaire score of >= 4 was 50.2% for formoterol 4.5 MUg (p = 0.0682 vs. placebo), 59.2% (p = 0.0004) for 9 MUg, and 41.3% for placebo. Reduction in reliever medication use was significantly greater with formoterol vs. placebo (9 MUg: -0.548, p < 0.001; 4.5 MUg: -0.274, p = 0.027), with 9 MUg being significantly superior to 4.5 MUg (-0.274, p = 0.029). Formoterol was well tolerated with the incidence and type of adverse events not being different for the three groups. CONCLUSIONS: Formoterol 4.5 MUg and 9 MUg bid was effective and well tolerated in patients with COPD; there was no difference between formoterol doses for the primary endpoint; however, an added value of formoterol 9 MUg over 4.5 MUg bid was observed for some secondary endpoints. TRIAL REGISTRATION: NCT00628862 (ClinicalTrials.gov); D5122C00001 (AstraZeneca Study code). PMID- 22085440 TI - Efficacy of a compulsory homework programme for increasing physical activity and healthy eating in children: the healthy homework pilot study. AB - BACKGROUND: Most physical activity and nutrition interventions in children focus on the school setting; however, evidence suggests that children are less active and have greater access to unhealthy food at home. The aim of this pilot study was to examine the efficacy of a compulsory homework programme for increasing physical activity and healthy eating in children. METHODS: The six-week 'Healthy Homework' programme and complementary teaching resource was developed under the guidance of an intersectoral steering group. Eight senior classes (year levels 5 6) from two diverse Auckland primary schools were randomly assigned into intervention and control groups. A total of 97 children (57 intervention, 40 control) aged 9-11 years participated in the evaluation of the intervention. Daily step counts were monitored immediately before and after the intervention using sealed multiday memory pedometers. Screen time, sports participation, active transport to and from school, and the consumption of fruits, vegetables, unhealthy foods and drinks were recorded concurrently in a 4-day food and activity diary. RESULTS: Healthy Homework resulted in a significant intervention effect of 2,830 steps.day-1 (95% CI: 560, 5,300, P = 0.013). This effect was consistent between sexes, schools, and day types (weekdays and weekend days). In addition, significant intervention effects were observed for vegetable consumption (0.83 servings.day-1, 95% CI: 0.24, 1.43, P = 0.007) and unhealthy food consumption (-0.56 servings.day-1, 95% CI: -1.05, -0.07, P = 0.027) on weekends but not weekdays, with no interactions with sex or school. Effects for all other variables were not statistically significant regardless of day type. CONCLUSIONS: Compulsory health-related homework appears to be an effective approach for increasing physical activity and improving vegetable and unhealthy food consumption in children. Further research in a larger study is required to confirm these initial results. PMID- 22085441 TI - Nuclease colicins and their immunity proteins. AB - It is more than 80 years since Gratia first described 'a remarkable antagonism between two strains of Escherichia coli'. Shown subsequently to be due to the action of proteins (or peptides) produced by one bacterium to kill closely related species with which it might be cohabiting, such bacteriocins have since been shown to be commonplace in the internecine warfare between bacteria. Bacteriocins have been studied primarily from the twin perspectives of how they shape microbial communities and how they penetrate bacteria to kill them. Here, we review the modes of action of a family of bacteriocins that cleave nucleic acid substrates in E. coli, known collectively as nuclease colicins, and the specific immunity (inhibitor) proteins that colicin-producing organisms make in order to avoid committing suicide. In a process akin to targeting in mitochondria, nuclease colicins engage in a variety of cellular associations in order to translocate their cytotoxic domains through the cell envelope to the cytoplasm. As well as informing on the process itself, the study of nuclease colicin import has also illuminated functional aspects of the host proteins they parasitize. We also review recent studies where nuclease colicins and their immunity proteins have been used as model systems for addressing fundamental problems in protein folding and protein-protein interactions, areas of biophysics that are intimately linked to the role of colicins in bacterial competition and to the import process itself. PMID- 22085442 TI - Effects of granulocyte colony-stimulating factor on electrocardiogram changes after carbon monoxide poisoning in rats. AB - Carbon monoxide (CO), which is produced by the incomplete combustion of hydrocarbons, has many toxic effects on different organs, especially the brain and heart. CO-induced cardiotoxicity leads to several deleterious effects, including electrocardiogram (ECG) abnormalities. The present study aimed to evaluate the protective effect of recombinant human granulocyte colony stimulation factor (G-CSF) on ECG after CO poisoning in rats. Single and multiple doses of G-CSF (10, 50, and 100 ug/kg) were administered to groups, each containing 5 male Wistar rats (16 groups for ECG analysis and 16 groups for pathological analysis). Rats were already exposed to CO at either 1,500 or 3,000 ppm concentrations for 60 minutes. ECG findings (e.g., ST-segment and T-wave changes), cardiac arrhythmias (e.g., heart blocks and ventricular and supraventricular arrhythmias), and histological changes were determined after G CSF administration. At 3,000 ppm, frequencies of ST elevation, depression, and T inversion in ECG were significantly reduced after G-CSF treatment. Also, some of the cardiac arrhythmias (e.g., atrioventricular block type 1 and 2) after CO poisoning were suppressed after G-CSF treatment. However, G-CSF did not show protective effects on cardiomyocyte pathological consequences in CO-poisoned rats. Therefore, G-CSF could protect against ECG changes after CO-induced cardiac ischemia, but did not affect pathological changes. PMID- 22085443 TI - An enzyme-coupled continuous fluorescence assay for farnesyl diphosphate synthases. AB - Farnesyl diphosphate synthase (FDPS) catalyzes the conversion of isopentenyl diphosphate and dimethylallyl diphosphate to farnesyl diphosphate, a crucial metabolic intermediate in the synthesis of cholesterol, ubiquinone, and prenylated proteins; consequently, much effort has gone into developing inhibitors that target FDPS. Currently most FDPS assays either use radiolabeled substrates and are discontinuous or monitor pyrophosphate release and not farnesyl diphosphate (FPP) creation. Here we report the development of a continuous coupled enzyme assay for FDPS activity that involves the subsequent incorporation of the FPP product of that reaction into a peptide via the action of protein farnesyltransferase (PFTase). By using a dansylated peptide whose fluorescence quantum yield increases upon farnesylation, the rate of FDPS catalyzed FPP production can be measured. We show that this assay is more sensitive than existing coupled assays, that it can be used to conveniently monitor FDPS activity in a 96-well plate format, and that it can reproduce IC(50) values for several previously reported FDPS inhibitors. This new method offers a simple, safe, and continuous method to assay FDPS activity that should greatly facilitate the screening of inhibitors of this important target. PMID- 22085444 TI - In-depth biophysical analysis of interactions between therapeutic antibodies and the extracellular domain of the epidermal growth factor receptor. AB - Targeting of the epidermal growth factor receptor (EGFR) with monoclonal antibodies has become an established antitumor strategy in clinical use or in late stages of drug development. The mAbs effector mechanisms have been widely analyzed based on in vivo or cell studies. Hereby we intend to complement these functional studies by investigating the mAb-EGFR interactions on a molecular level. Surface plasmon resonance, isothermal titration calorimetry, and static light scattering were employed to characterize the interactions of matuzumab, cetuximab, and panitumumab with the extracellular soluble form ecEGFR. The kinetic and thermodynamic determinants dissected the differences in mAbs binding mechanism toward ecEGFR. The quantitative stoichiometric data clearly demonstrated the bivalent binding of the mAbs to two ecEGFR molecules. Our results complement earlier studies on simultaneous binding of cetuximab and matuzumab. The antibodies retain their bivalent binding mode achieving a 1:2:1 complex formation. Interestingly the binding parameters remain nearly constant for the individual antibodies in this ternary assembly. In contrast the binding of panitumumab is almost exclusive either by directly blocking the accessibility for the second antibody or by negative allosteric modulation. Overall we provide a comprehensive biophysical dataset on binding parameters, the complex assembly, and relative epitope accessibility for therapeutic anti-EGFR antibodies. PMID- 22085445 TI - Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. AB - BACKGROUND: This work aimed to study the homing evidence and the reparative effect of mesenchymal stem cells (MSCs) in the healing process of induced osteoarthritis in experimental animal model (donkeys). METHODS: Twenty-seven donkeys were equally divided into 3 groups based on the observation period after induction of arthritis (3, 6 and 9 weeks) to achieve different degrees of osteoarthritis. Each group was subdivided into three subgroups of three animals each based on the follow-up period (1, 2 and 6 months) after treatment. The induction was done through intra-articular (IA) injection of 2 ml of Amphotericin B in both carpal joints. MSCs were harvested in a separate procedure, labeled with green fluorescent protein (GFP) using monster GFP vector and suspended in hyaluronic acid for IA injection. Treatment approaches consisted of cell treatment using MSCs suspended in 3 ml of hyaluronic acid (HA) for the right carpal joint; and using the same amount of (HA) but without MSCs for the left contralateral carpal joint to serve as a control. Animals were assessed clinically and radiologically before and after treatment. Synovial fluid was also evaluated. Histopathologically; articular cartilage structural changes, reduction of articular cartilage matrix staining, osteophyte formation, and subchondral bone plate thickening were graded. Data was summarized using median and percentile for scores of histopathologic grading. Comparison between groups was done using non-parametric Mann Whitney test. RESULTS: The reparative effect of MSCs was significant both clinically and radiologically in all treated groups (P < 0.05) compared to the control groups. Fluorescence microscopy of sections of the cell-treated joints of all animals indicated that the GFP-transduced injected cells have participated effectively in the reparative process of the damaged articular surface and have integrated within the existing articular cartilage. The cells were associated with the surface of the cartilage and, were also detected in the interior. CONCLUSIONS: Homing was confirmed by the incorporation of injected GFP-labeled MSCs within the repaired newly formed cartilage. Significant recovery proves that the use of IA injection of autologous MSCs is a viable and a practical option for treating different degrees of osteoarthritis. PMID- 22085446 TI - Molecular characteristics of bovine virus diarrhoea virus 1 isolates from Turkey: approaches for an eradication programme. AB - Forty pestivirus isolates sampled from cattle in Turkey between 2002 and 2007 were characterized according to 5' untranslated region (5'UTR) sequences and autoprotease (N(pro) ) gene sequences. The sampling of Bovine virus diarrhoea viruses (BVDVs) from 15 farms in five different regions indicated that BVDV 1-l (18/40, 45%) was the predominant genotype in Turkey; the samples also contained the genotypes 1-f (10/40, 25%), 1-b (7/40, 17.5%), 1-d (3/40, 7.5%), and 1-a (2/40, 5%), respectively. PMID- 22085447 TI - Grafted poly(1->4-beta-glucan) strands on silica: a comparative study of surface reactivity as a function of grafting density. AB - Grafted poly(beta-glucan) (beta-glu) strands on the surface of silica are synthesized with varying degrees of grafting density, and display an amorphous like environment via (13)C CP/MAS NMR spectroscopy. Thermal gravimetric analysis of these materials under oxidative conditions shows increased beta-glu thermal stability with higher degrees of grafting density. The range of temperature stability between the most and least hydrogen-bound grafted beta-glu strands spans 321 to 260 degrees C. This range is bound by the combustion temperature previously measured for crystalline and amorphous cellulose, with the former having greater oxidative stability, and is likely controlled by the extent of hydrogen bonding of a grafted beta-glu strand with the underlying silica surface. When using these materials as reactants for glycosidic bond hydrolysis, the total number of reducing ends formed during reaction is quantified using a BCA colorimetric assay. Results demonstrate that the material with greatest interaction with silica surface silanols undergoes hydrolysis at an initial rate that is 6-fold higher than the material with the lowest degree of such interaction. The role of the surface as a reactive interface that can endow oxidative stability and promote hydrolysis activity has broad implications for surface-catalyzed processes dealing with biomass-derived polymers. PMID- 22085448 TI - CB1 receptor activation inhibits neuronal and astrocytic intermediary metabolism in the rat hippocampus. AB - Cannabinoid CB1 receptor (CB1R) activation decreases synaptic GABAergic and glutamatergic transmission and it also controls peripheral metabolism. Here we aimed at testing with 13C NMR isotopomer analysis whether CB1Rs could have a local metabolic role in brain areas having high CB1R density, such as the hippocampus. We labelled hippocampal slices with the tracers [2-13C]acetate, which is oxidized in glial cells, and [U-13C]glucose, which is metabolized both in glia and neurons, to evaluate metabolic compartmentation between glia and neurons. The synthetic CB1R agonist WIN55212-2 (1 MUM) significantly decreased the metabolism of both [2-13C]acetate (-11.6+/-2.0%) and [U-13C]glucose (-11.2+/ 3.4%) in the tricarboxylic acid cycle that contributes to the glutamate pool. WIN55212-2 also significantly decreased the metabolism of [U-13C]glucose (-11.7+/ 4.0%) but not that of [2-13C]acetate contributing to the pool of GABA. These effects of WIN55212-2 were prevented by the CB1R antagonist AM251 (500 nM). These results thus suggest that CB1Rs might be present also in hippocampal astrocytes besides their well-known neuronal localization. Indeed, confocal microscopy analysis revealed the presence of specific CB1R immunoreactivity in astrocytes and pericytes throughout the hippocampus. In conclusion, CB1Rs are able to control hippocampal intermediary metabolism in both neuronal and glial compartments, which suggests new alternative mechanisms by which CB1Rs control cell physiology and afford neuroprotection. PMID- 22085450 TI - How scientists use social media to communicate their research. AB - Millions of people all over the world are constantly sharing an extremely wide range of fascinating, quirky, funny, irrelevant and important content all at once. Even scientists are no strangers to this trend. Social media has enabled them to communicate their research quickly and efficiently throughout each corner of the world. But which social media platforms are they using to communicate this research and how are they using them? One thing is clear: the range of social media platforms that scientists are using is relatively vast and dependent on discipline and sentiment. While the future of social media is unknown, a combination of educated speculation and persuasive fact points to the industry's continual growth and influence. Thus, is that not only are scientists utilizing social media to communicate their research, they must. The ability to communicate to the masses via social media is critical to the distribution of scientific information amongst professionals in the field and to the general population. PMID- 22085449 TI - Amygdala-prefrontal pathways and the dopamine system affect nociceptive responses in the prefrontal cortex. AB - BACKGROUND: We previously demonstrated nociceptive discharges to be evoked by mechanical noxious stimulation in the prefrontal cortex (PFC). The nociceptive responses recorded in the PFC are conceivably involved in the affective rather than the sensory-discriminative dimension of pain. The PFC receives dense projection from the limbic system. Monosynaptic projections from the basolateral nucleus of the amygdala (BLA) to the PFC are known to produce long-lasting synaptic plasticity. We examined effects of high frequency stimulation (HFS) delivered to the BLA on nociceptive responses in the rat PFC. RESULTS: HFS induced long lasting suppression (LLS) of the specific high threshold responses of nociceptive neurons in the PFC. Microinjection of N-methyl-D-aspartic acid (NMDA) receptor antagonists (2-amino-5-phosphonovaleric acid (APV), dizocilpine (MK-801)) and also metabotropic glutamate receptor (mGluR) group antagonists (alpha-methyl-4-carboxyphenylglycine (MCPG), and 2-[(1S,2S)-2-carboxycyclopropyl] 3-(9H-xanthen-9-yl)-D-alanine (LY341495)), prevented the induction of LLS of nociceptive responses. We also examined modulatory effects of dopamine (DA) on the LLS of nociceptive responses. With depletion of DA in response to 6 hydroxydopamine (6-OHDA) injection into the ipsilateral forebrain bundle, LLS of nociceptive responses was decreased, while nociceptive responses were normally evoked. Antagonists of DA receptor subtypes D2 (sulpiride) and D4 (3-{[4-(4 chlorophenyl) piperazin-1-yl] methyl}-1H-pyrrolo [2, 3-b] pyridine (L-745,870)), microinjected into the PFC, inhibited LLS of nociceptive responses. CONCLUSIONS: Our results indicate that BLA-PFC pathways inhibited PFC nociceptive cell activities and that the DA system modifies the BLA-PFC regulatory function. PMID- 22085451 TI - Composition and hydrothermal pretreatment and enzymatic saccharification performance of grasses and legumes from a mixed-species prairie. AB - BACKGROUND: Mixtures of prairie species (mixed prairie species; MPS) have been proposed to offer important advantages as a feedstock for sustainable production of fuels and chemicals. Therefore, understanding the performance in hydrothermal pretreatment and enzymatic hydrolysis of select species harvested from a mixed prairie is valuable in selecting these components for such applications. This study examined composition and sugar release from the most abundant components of a plot of MPS: a C3 grass (Poa pratensis), a C4 grass (Schizachyrium scoparium), and a legume (Lupinus perennis). Results from this study provide a platform to evaluate differences between grass and leguminous species, and the factors controlling their recalcitrance to pretreatment and enzymatic hydrolysis. RESULTS: Significant differences were found between the grass and leguminous species, and between the individual anatomical components that influence the recalcitrance of MPS. We found that both grasses contained higher levels of sugars than did the legume, and also exhibited higher sugar yields as a percentage of the maximum possible from combined pretreatment and enzymatic hydrolysis. Furthermore, particle size, acid-insoluble residue (AcIR), and xylose removal were not found to have a direct significant effect on glucan digestibility for any of the species tested, whereas anatomical composition was a key factor in both grass and legume recalcitrance, with the stems consistently exhibiting higher recalcitrance than the other anatomical fractions. CONCLUSIONS: The prairie species tested in this study responded well to hydrothermal pretreatment and enzymatic saccharification. Information from this study supports recommendations as to which plant types and species are more desirable for biological conversion in a mixture of prairie species, in addition to identifying fractions of the plants that would most benefit from genetic modification or targeted growth. PMID- 22085452 TI - On the symmetry of siblings: automated single-cell tracking to quantify the behavior of hematopoietic stem cells in a biomimetic setup. AB - The interplay between hematopoietic stem and progenitor cells (HSPC) and their local microenvironment is a key mechanism for the organization of hematopoiesis. To quantitatively study this process, a time-resolved analysis of cellular dynamics at the single-cell level is an essential prerequisite. One way to generate sufficient amounts of appropriate data is automatic single-cell tracking using time-lapse video microscopy. We describe and apply newly developed computational algorithms that allow for an automated generation of high-content data of single-cell characteristics at high temporal and spatial resolution, together with the reconstruction and statistical evaluation of complete genealogical histories. This methodology has been applied to the particular example of purified primary human HSPCs in bioengineered culture conditions. The combination of genealogical information and dynamic profiles of cellular properties identified a marked symmetry between sibling HSPCs regarding cell cycle time, but also migration speed and growth kinetics. Furthermore, we demonstrate that this symmetry of HSPC siblings can be altered by exogenous cues of the local biomimetic microenvironment. Using the example of HSPC growth in biomimetic culture systems, we show that our approach provides a valuable tool for the quantitative analysis of dynamic single-cell features under defined in vitro conditions, allowing for integration of functional and genealogical data. The efficiency and accuracy of our approach pave the way for new and intriguing insights into the organizational principles of developmental patterns and the respective influence of exogenous cues not limited to the study of primary HSPCs. PMID- 22085455 TI - An exploration of search patterns and credibility issues among older adults seeking online health information. AB - The Internet is an important resource for health information, among younger and older people alike. Unfortunately, there are limitations associated with online health information. Research is needed on the quality of information found online and on whether users are being critical consumers of the information they find. Also, there is a need for research investigating online use among adults aged 65 and over - a rapidly growing demographic of Internet users. The current study presents important descriptive data about the search patterns of older adults seeking online health information, the types of health topics they research, and whether they consider credibility issues when retrieving online health information. A comparison is also made between search strategies used in printed text and hypertext environments. The results, which have implications with respect to credibility issues, highlight the need to increase awareness about critical searching skills among older adult Internet users. PMID- 22085453 TI - Dipeptidyl peptidase IV (DPPIV/CD26) inhibition does not improve engraftment of unfractionated syngeneic or allogeneic bone marrow after nonmyeloablative conditioning. AB - In order to develop minimally toxic bone marrow transplantation (BMT) protocols suitable for use in a wider range of indications, it is important to identify ways to enhance BM engraftment at a given level of recipient conditioning. CXCL12/stromal cell-derived factor-1alpha plays a crucial physiological role in homing of hematopoietic stem cells to BM. It is regulated by the ectopeptidase dipeptidyl peptidase IV (DPPIV; DPP4) known as CD26, which cleaves dipeptides from the N-terminus of polypeptide chains. Blocking DPPIV enzymatic activity had a beneficial effect on hematopoietic stem cell engraftment in various but very specific experimental settings. Here we investigated whether inhibition of DPPIV enzymatic activity through Diprotin A or sitagliptin (Januvia) improves BM engraftment in nonmyeloablative murine models of syngeneic (i.e., CD45-congenic) and allogeneic (i.e., Balb/c to B6) BMT (1 Gy total body irradiation, 10-15 * 10(6) unseparated BM cells/mouse). Neither Diprotin A administered in vivo at the time of BMT and/or used for in vitro pretreatment of BM nor sitagliptin administered in vivo had a detectable effect on the level of multilineage chimerism (follow-up >20 weeks). Similarly, sitagliptin did not enhance chimerism after allogeneic BMT, even though DPPIV enzymatic activity measured in serum was profoundly inhibited (>98% inhibition at peak exposure). Our results provide evidence that DPPIV inhibition via Diprotin A or sitagliptin does not improve engraftment of unseparated BM in a nonmyeloablative BMT setting. PMID- 22085456 TI - Long-term follow-up in patients with retinopathy of prematurity. PMID- 22085457 TI - 15-day-old neonate with cystic swelling. Congenital bilateral dacryocystoceles. PMID- 22085458 TI - Physician etiquette in pediatric ophthalmology. PMID- 22085460 TI - Screening for amblyopia. PMID- 22085461 TI - Combined hamartoma of the retina and retinal pigment epithelium. PMID- 22085462 TI - Foam granulation: new developments in pharmaceutical solid oral dosage forms using twin screw extrusion machinery. AB - This paper investigates foam granulation in a twin screw extruder as a new continuous wet granulation technique for pharmaceutical powder drug formulations. Foamed aqueous binder has a reportedly lower soak-to-spread ratio than drop or spray liquid addition in batch granulation. This work demonstrates a twin screw extruder configuration for foam granulation and subsequently compares the new approach against liquid injection in the granulation of alpha-lactose monohydrate with a methylcellulose binder. Trials were conducted at high powder output rates (20-40 kg/h) and high screw speeds (220-320 RPM) with two screw configurations. Process stability improved with the new technique allowing granulation with less binder. The extruded mass maintained a low exit temperature, being insensitive to operating conditions unlike the liquid injection approach, where temperatures rose significantly as flow rate increased. The particle size distribution by foam granulation reflected a more uniformly wetted mass with larger granule growth noted even for conditions where dry powder exited by liquid injection. Other factors were found similar between the two binder delivery methods such as consumed mechanical energy, as well as fracture strength and compressibility of produced granules. PMID- 22085463 TI - Efficient production of chimeric human papillomavirus 16 L1 protein bearing the M2e influenza epitope in Nicotiana benthamiana plants. AB - BACKGROUND: Human papillomavirus 16 (HPV-16) L1 protein has the capacity to self assemble into capsomers or virus-like particles (VLPs) that are highly immunogenic, allowing their use in vaccine production. Successful expression of HPV-16 L1 protein has been reported in plants, and plant-produced VLPs have been shown to be immunogenic after administration to animals. RESULTS: We investigated the potential of HPV-16 L1 to act as a carrier of two foreign epitopes from Influenza A virus: (i) M2e2-24, ectodomain of the M2 protein (M2e), that is highly conserved among all influenza A isolates, or (ii) M2e2-9, a shorter version of M2e containing the N-terminal highly conserved epitope, that is common for both M1 and M2 influenza proteins. A synthetic HPV-16 L1 gene optimized with human codon usage was used as a backbone gene to design four chimeric sequences containing either the M2e2-24 or the M2e2-9 epitope in two predicted surface exposed L1 positions. All chimeric constructs were transiently expressed in plants using the Cowpea mosaic virus-derived expression vector, pEAQ-HT. Chimeras were recognized by a panel of linear and conformation-specific anti HPV-16 L1 MAbs, and two of them also reacted with the anti-influenza MAb. Electron microscopy showed that chimeric proteins made in plants spontaneously assembled in higher order structures, such as VLPs of T = 1 or T = 7 symmetry, or capsomers. CONCLUSIONS: In this study, we report for the first time the transient expression and the self-assembly of a chimeric HPV-16 L1 bearing the M2e influenza epitope in plants, representing also the first record of a successful expression of chimeric HPV-16 L1 carrying an epitope of a heterologous virus in plants. This study further confirms the usefulness of human papillomavirus particles as carriers of exogenous epitopes and their potential relevance for the production in plants of monovalent or multivalent vaccines. PMID- 22085464 TI - Neuromelanin is an immune stimulator for dendritic cells in vitro. AB - BACKGROUND: Parkinson's disease (PD) is characterized at the cellular level by a destruction of neuromelanin (NM)-containing dopaminergic cells and a profound reduction in striatal dopamine. It has been shown recently that anti-melanin antibodies are increased in sera of Parkinson patients, suggesting that NM may act as an autoantigen. In this study we tested whether NM is being recognized by dendritic cells (DCs), the major cell type for inducing T- and B-cell responses in vivo. This recognition of NM by DCs is a prerequisite to trigger an adaptive autoimmune response directed against NM-associated structures. RESULTS: Murine DCs were treated with NM of substantia nigra (SN) from human subjects or with synthetic dopamine melanin (DAM). DCs effectively phagocytized NM and subsequently developed a mature phenotype (CD86(high)/MHCII(high)). NM-activated DCs secreted the proinflammatory cytokines IL-6 and TNF-alpha. In addition, they potently triggered T cell proliferation in a mixed lymphocyte reaction, showing that DC activation was functional to induce a primary T cell response. In contrast, DAM, which lacks the protein and lipid components of NM but mimics the dopamine-melanin backbone of NM, had only very little effect on DC phenotype and function. CONCLUSIONS: NM is recognized by DCs in vitro and triggers their maturation. If operative in vivo, this would allow the DC-mediated transport and presentation of SN antigens to the adaptive immune system, leading to autoimmmunity in susceptible individuals. Our data provide a rationale for an autoimmune-based pathomechanism of PD with NM as the initial trigger. PMID- 22085465 TI - Interactions of a hydrophobically modified polycation with zwitterionic lipid membranes. AB - The interactions between synthetic polycations and phospholipid bilayers play an important role in some biophysical applications such as gene delivery or antibacterial usage. Despite extensive investigation into the nature of these interactions, their physical and molecular bases remain poorly understood. In this Article, we present the results of our studies on the impact of a hydrophobically modified strong polycation on the properties of a zwitterionic bilayer used as a model of the mammalian cellular membrane. The study was carried out using a set of complementary experimental methods and molecular dynamic (MD) simulations. A new polycation, poly(allyl-N,N-dimethyl-N-hexylammonium chloride) (polymer 3), was synthesized, and its interactions with liposomes composed of 2 oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) were examined using dynamic light scattering (DLS), zeta potential measurements, and cryo-transmission electron microscopy (cryo-TEM). Our results have shown that polymer 3 can efficiently associate with and insert into the POPC membrane. However, it does not change its lamellar structure, as was demonstrated by cryo-TEM. The influence of polymer 3 on the membrane functionality was studied by leakage experiments applying a fluorescence dye (calcein) encapsulated in the phospholipid vesicles. The MD simulations of model systems reveal that polymer 3 promotes formation of hydrophilic pores in the membrane, thus increasing considerably its permeability. PMID- 22085466 TI - Extraction and inhibition of enzymatic activity of botulinum neurotoxins /B1, /B2, /B3, /B4, and /B5 by a panel of monoclonal anti-BoNT/B antibodies. AB - BACKGROUND: Botulism is caused by botulinum neurotoxins (BoNTs), extremely toxic proteins which can induce respiratory failure leading to long-term intensive care or death. Treatment for botulism includes administration of antitoxins, which must be administered early in the course of the intoxication; therefore, rapid determination of human exposure to BoNT is an important public health goal. In previous work, our laboratory reported on Endopep-MS, a mass spectrometry-based activity method for detecting and differentiating BoNT/A, /B, /E, and /F in clinical samples. We also demonstrated that antibody-capture is effective for purification and concentration of BoNTs from complex matrices such as clinical samples. However, some antibodies inhibit or neutralize the enzymatic activity of BoNT, so the choice of antibody for toxin extraction is critical. RESULTS: In this work, we evaluated 24 anti-BoNT/B monoclonal antibodies (mAbs) for their ability to inhibit the in vitro activity of BoNT/B1, /B2, /B3, /B4, and /B5 and to extract those toxins. Among the mAbs, there were significant differences in ability to extract BoNT/B subtypes and inhibitory effect on BoNT catalytic activity. Some of the mAbs tested enhanced the in vitro light chain activity of BoNT/B, suggesting that BoNT/B may undergo conformational change upon binding some mAbs. CONCLUSIONS: In addition to determining in vitro inhibition abilities of a panel of mAbs against BoNT/B1-/B5, this work has determined B12.2 and 2B18.2 to be the best mAbs for sample preparation before Endopep-MS. These mAb characterizations also have the potential to assist with mechanistic studies of BoNT/B protection and treatment, which is important for studying alternative therapeutics for botulism. PMID- 22085468 TI - The 2011 International Psychogeriatric Association Junior Research Awards in Psychogeriatrics. PMID- 22085467 TI - Assessment of the kidneys: magnetic resonance angiography, perfusion and diffusion. AB - Renal magnetic resonance (MR) imaging has undergone major improvements in the past several years. This review focuses on the technical basics and clinical applications of MR angiography (MRA) with the goal of enabling readers to acquire high-resolution, high quality renal artery MRA. The current role of contrast agents and their safe use in patients with renal impairment is discussed. In addition, an overview of promising techniques on the horizon for renal MR is provided. The clinical value and specific applications of renal MR are critically discussed. PMID- 22085469 TI - Ten rules to assess and manage the acutely deteriorating patient: a practical mnemonic. AB - The acutely deteriorating patient is a challenge to even the most seasoned provider. The ability to diagnosis the underlying condition quickly and accurately is vital to a successful outcome. We present a review of 10 critical aspects in the management of the crashing patient, based on up-to-date guidelines and organized as an easily remembered mnemonic. The A-A-B-B-C-C-D-D-E-E's of the deteriorating patient address many key pearls and current recommendations to give physicians an added advantage in the moment of crisis. PMID- 22085470 TI - To evaluate the effect of addition of an anionic surfactant on solid dispersion using model drug indomethacin. AB - Formation of solid dispersion also known as high energy solids is one of the most successful concepts to improve dissolution profile of poorly water-soluble drugs. Use of surfactants in formulation is one of the methods to increase solubility profile. In this research, we have used model drug, a weak acid (indomethacin) together with polymer (PVP) and anionic surfactant (sodium lauryl sulfate (SLS)) in different concentrations to study the effect of incorporation of SLS in solid dispersion. Three ratios and control were prepared. Physical characterization was performed using modulated differential scanning calorimetry (MDSC), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Critical micelle concentration (CMC) measurements were conducted to see the effect of SLS on dissolution media. Dissolution studies were performed in hydrochloric acid buffer (pH 1.2 buffer), purified water and phosphate buffer (pH 7.4), respectively. Interestingly, depending upon addition of SLS into the system, release profiles were changed. SLS incorporated internally in a solid dispersion gave the highest release. PMID- 22085471 TI - Atypical mood stabilizers: a new role for neuroleptics? PMID- 22085472 TI - Subthreshold bipolarity: diagnostic issues and challenges. AB - BACKGROUND: Research suggests that current diagnostic criteria for bipolar disorders may fail to include milder, but clinically significant, bipolar syndromes and that a substantial percentage of these conditions are diagnosed, by default, as unipolar major depression. Accordingly, a number of researchers have argued for the upcoming 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to better account for subsyndromal hypomanic presentations. METHODS: The present paper is a critical review of research on subthreshold bipolarity, and an assessment of some of the challenges that researchers and clinicians might face if the DSM-5 were designed to systematically document subsyndromal hypomanic presentations. RESULTS: Individuals with major depressive disorder (MDD) who display subsyndromal hypomanic features, not concurrent with a major depressive episode, have a more severe course compared to individuals with MDD and no hypomanic features, and more closely resemble individuals with bipolar disorder on a number of clinical validators. CONCLUSION: There are clinical and scientific reasons for systematically documenting subsyndromal hypomanic presentations in the assessment and diagnosis of mood disorders. However, these benefits are balanced with important challenges, including (i) the difficulty in reliably identifying subsyndromal hypomanic presentations, (ii) operationalizing subthreshold bipolarity, (iii) differentiating subthreshold bipolarity from borderline personality disorder, (iv) the risk of over-diagnosing bipolar spectrum disorders, and (v) uncertainties about optimal interventions for subthreshold bipolarity. PMID- 22085473 TI - White matter microstructure in untreated first episode bipolar disorder with psychosis: comparison with schizophrenia. AB - OBJECTIVES: White matter abnormalities have been reported in bipolar disorder. The present study aimed to investigate white matter integrity in untreated first episode patients with psychotic bipolar disorder using diffusion tensor imaging, and to compare observations with those from untreated first episode schizophrenia patients. METHODS: Fractional anisotropy and mean diffusivity were measured in first episode psychotic patients with bipolar disorder (n = 13) or schizophrenia (n = 21) and healthy individuals (n = 18). Group differences were evaluated using voxel-based morphometry. Axial and radial diffusivity were examined in regions with altered fractional anisotropy in post-hoc analyses. RESULTS: Patients with bipolar disorder showed lower fractional anisotropy than healthy controls in several white matter tracts. Compared with schizophrenia patients, bipolar disorder patients showed lower fractional anisotropy in the cingulum, internal capsule, posterior corpus callosum, tapetum, and occipital white matter including posterior thalamic radiation and inferior longitudinal fasciculus/inferior fronto occipital fasciculus. Lower fractional anisotropy in bipolar disorder was characterized by increased radial diffusion rather than axial diffusion along the orientation of fiber tracts. Across several white matter tracts, both patient groups showed greater mean diffusivity than healthy individuals. CONCLUSIONS: Selectively increased radial diffusivity in bipolar disorder patients suggests structural disorganization in fiber tract coherence of neurodevelopmental origin or alterations in myelin sheaths along fiber tracts. In contrast, increased isotropic diffusion along white matter tracts in schizophrenia patients with alterations in both radial and axial diffusivity suggests increased water content outside the axonal space. Thus, the present results suggest that different pathophysiological mechanisms may underlie white matter microstructural abnormalities in bipolar disorder and schizophrenia. PMID- 22085474 TI - Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population. AB - OBJECTIVES: Dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most consistent findings in the pathophysiology of mood disorders. The potential role of genes related to HPA axis function has been investigated extensively in major depression. However, in bipolar disorder (BPD) such studies are scarce. We performed a systematic HapMap-based association study of six genes crucial for HPA axis function in relation to BPD. METHODS: Haplotype tagging single nucleotide polymorphisms (htSNPs) were selected in order to identify all haplotypes with a frequency of more than 1% in the genes encoding the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), corticotrophin releasing hormone receptor 1 (CRH-R1) and 2 (CRH-R2), CRH binding protein (CRH BP), and FK binding protein 5 (FKBP5). This resulted in a total selection of 225 SNPs that were genotyped and analyzed in 309 BPD patients and 364 matched control individuals all originating from an isolated northern Swedish population. RESULTS: Consistent evidence for an association with BPD was found for NR3C1, the gene encoding GR. Almost all SNPs in two adjacent haplotype blocks contributed to the positive signal, comprised of significant single marker, sliding window, and haplotype-specific p-values. All these results point to a moderately frequent (10 15%) susceptibility haplotype covering the entire coding region and 3' untranslated region (UTR) of NR3C1. CONCLUSIONS: This study contributes to the growing evidence for a role of the glucocorticoid receptor gene (NR3C1) in vulnerability to mood disorders, and BPD in particular, and warrants further in vitro investigation of the at-risk haplotypes with respect to disease etiology. However, this association might be restricted to this specific population, as it is observed in a rather small sample from an isolated population without replication, and data from large meta-analyses for genome-wide association studies in BPD do not show the GR as a very strong candidate. PMID- 22085475 TI - Neonatal antibodies to infectious agents and risk of bipolar disorder: a population-based case-control study. AB - OBJECTIVE: There is a substantial evidence base linking prenatal exposure to infectious agents and an increased risk of schizophrenia. However, there has been less research examining the potential for these exposures to also contribute to risk for bipolar disorder. The aim of this study was to examine the association between neonatal markers of selected prenatal infections and risk for bipolar disorder. METHODS: Using population-based Danish registers, we examined 127 individuals with a diagnosis of bipolar disorder, and 127 sex and day-of-birth individually matched controls. Based on neonatal dried blood spots, we measured antibodies to herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), cytomegalovirus (CMV), and Toxoplasma gondii. Relative risks were calculated for the matched pairs when examined for optical density units for antibodies to each of the infectious agents. RESULTS: There was no association between any of the neonatal markers of prenatal infection and risk of bipolar disorder. CONCLUSIONS: In contrast with studies of schizophrenia, our analysis does not support maternal infection with HSV-1, HSV-2, CMV, or Toxoplasma gondii as risk factors for bipolar disorder. However, larger study samples are needed, and data on, for example, specific serotypes of Toxoplasma and indicators of the timing of maternal infection are still warranted. PMID- 22085476 TI - Evidence of associations between bipolar disorder and the brain-derived neurotrophic factor (BDNF) gene. AB - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has important roles in neural cell growth and differentiation. Despite multiple lines of evidence suggesting BDNF as a possible contributor to the pathogenesis of bipolar disorder (BD), the results of genetic association studies have been mixed. We hypothesize that BDNF gene polymorphisms may confer increased susceptibility to BD. METHODS: Using a cohort of multiplex bipolar families, we performed family-based association testing to look for associations between BD and eight single nucleotide polymorphisms (SNPs) from BDNF. RESULTS: We found associations (p < 0.05) between BD and six of the eight SNPs analysed, including two SNPs not previously investigated in association studies. We were able to replicate associations previously found between BD and the Val66Met polymorphism of BDNF (rs6265) and the SNPs rs1519480 and rs12273363. We also found evidence of an association between rs11030107 and BD that was not found in a previous study. CONCLUSIONS: Our results support the hypothesis that some BDNF gene polymorphisms may be contributing factors in the pathogenesis of BD. Our study also adds to the body of evidence associating the functional Val66Met polymorphism of BDNF with BD. PMID- 22085477 TI - Sensitivity to positive and negative feedback in euthymic patients with bipolar I disorder: the last episode makes the difference. AB - OBJECTIVES: It is unclear whether abnormalities in cognition and motivation, such as altered feedback processing, observed during euthymia represent trait markers of bipolar I disorder (BD-I) or scars from previous episodes that also occur in major depression (MD). The present research examines how previous episodes influence sensitivity to positive and negative feedback, applying multiple hierarchical regression analysis with number of past depressive and manic episodes, residual mood symptoms, affective quality of the last episode, time in remission, medication, illness severity, and age as predictors. METHODS: The study included 23 euthymic patients with BD-I, 19 remitted patients with MD, and 19 healthy persons who underwent a task which discriminates whether persons learn better from negative or positive feedback. RESULTS: For both models, predicting sensitivity to positive [F((5,60)) = 6.50, p = 0.001, adjusted R(2) = 0.22] and negative feedback [F((5,60)) = 5.12, p = 0.001, adjusted R(2) = 0.22], the quality of the last affective episode was the only significant predictor. BD-I patients who last experienced a manic episode learned well from positive but not negative feedback, whereas BD-I patients who last experienced a depressive episode showed the opposite pattern. CONCLUSIONS: Our data identify differences in response to positive and negative consequences carrying over into the euthymic state that are qualitatively related to the polarity of the preceding episode, whereas other disease-related variables had no significant influence. This sheds new light on previous inconsistent data in euthymic BD-I patients and could also guide tailored treatment. PMID- 22085478 TI - Cognitions in bipolar affective disorder and unipolar depression: imagining suicide. AB - OBJECTIVE: Bipolar disorder has the highest rate of suicide of all the psychiatric disorders. In unipolar depression, individuals report vivid, affect laden images of suicide or the aftermath of death (flashforwards to suicide) during suicidal ideation but this phenomenon has not been explored in bipolar disorder. Therefore the authors investigated and compared imagery and verbal thoughts related to past suicidality in individuals with bipolar disorder (n = 20) and unipolar depression (n = 20). METHODS: The study used a quasi experimental comparative design. The Structured Clinical Interview for DSM-IV was used to confirm diagnoses. Quantitative and qualitative data were gathered through questionnaire measures (e.g., mood and trait imagery use). Individual interviews assessed suicidal cognitions in the form of (i) mental images and (ii) verbal thoughts. RESULTS: All participants reported imagining flashforwards to suicide. Both groups reported greater preoccupation with these suicide-related images than with verbal thoughts about suicide. However, compared to the unipolar group, the bipolar group were significantly more preoccupied with flashforward imagery, rated this imagery as more compelling, and were more than twice as likely to report that the images made them want to take action to complete suicide. In addition, the bipolar group reported a greater trait propensity to use mental imagery in general. CONCLUSIONS: Suicidal ideation needs to be better characterized, and mental imagery of suicide has been a neglected but potentially critical feature of suicidal ideation, particularly in bipolar disorder. Our findings suggest that flashforward imagery warrants further investigation for formal universal clinical assessment procedures. PMID- 22085479 TI - Personality traits in bipolar disorder type I: a sib-pair analysis. AB - OBJECTIVE: The aim of this study was to compare temperament and character traits among patients with bipolar disorder (BD), their siblings, and healthy controls (HCs) in order to examine whether personality traits are related to the genetic vulnerability to develop BD. METHODS: Using the Temperament and Character Inventory, we assessed 204 subjects: 67 euthymic outpatients with bipolar disorder type I, 67 siblings without BD, and 70 HCs. RESULTS: Scores on harm avoidance, novelty seeking, and self-transcendence were significantly higher among patients with BD than among HCs, whereas those on self-directedness and cooperativeness were significantly lower. Siblings showed higher scores on harm avoidance and lower scores on self-directedness than did HCs. As some of the siblings presented at least one lifetime psychiatric disorder other than BD (n = 35), we examined the subset of siblings who had no lifetime psychiatric disorder (n = 32). This group showed statistically higher harm avoidance scores than HCs. CONCLUSIONS: Our results suggest that the harm avoidance temperament trait and, to a lesser extent, the self-directedness character trait may represent vulnerability factors for BD. PMID- 22085480 TI - Dimensional psychopathology in offspring of parents with bipolar disorder. AB - OBJECTIVES: To compare the dimensional psychopathology in offspring of parents with bipolar disorder (BP) with offspring of community control parents as assessed by the Child Behavior Checklist (CBCL). METHODS: Offspring of parents with BP, who were healthy or had non-BP disorders (any psychiatric disorder other than BP; n = 319) or who had bipolar spectrum disorders (n = 35), and offspring of community controls (n = 235) ages 6-18 years were compared using the CBCL, the CBCL-Dysregulation Profile (CBCL-DP), and a sum of the CBCL items associated with mood lability. The results were adjusted for multiple comparisons and for any significant between-group demographic and clinical differences in both biological parents and offspring. RESULTS: With few exceptions, several CBCL (e.g., Total, Internalizing, and Aggression Problems), CBCL-DP, and mood lability scores in non BP offspring of parents with BP were significantly higher than in offspring of control parents. In addition, both groups of offspring showed significantly lower scores in most scales when compared with offspring of parents with BP who had already developed BP. Similar results were obtained when analyzing the rates of subjects with CBCL T-scores that were two standard deviations or higher above the mean. CONCLUSIONS: Even before developing BP, offspring of parents with BP had more severe and higher rates of dimensional psychopathology than offspring of control parents. Prospective follow-up studies in non-BP offspring of parents with BP are warranted to evaluate whether these dimensional profiles are prodromal manifestations of mood or other disorders, and can predict those who are at higher risk to develop BP. PMID- 22085481 TI - Six-month functional outcome of a bipolar disorder cohort in the context of a specialized-care program. AB - OBJECTIVES: A marked disparity between functional recovery and symptomatic improvement has been demonstrated in bipolar disorder. However, most of the previous studies have been conducted in the United States, and there is little prospective research from Europe on this topic. The main objective of the present six-month follow-up study was to assess functioning in a sample of Spanish bipolar disorder patients following an acute episode or subsyndromal state. Additionally, we also evaluated the sensitivity to change of the Functioning Assessment Short Test (FAST). METHODS: A total of 97 bipolar disorder patients with syndromal (n = 59) or subsyndromal (n = 38) symptoms were evaluated using the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale. The FAST was the primary measure to assess multiple areas of psychosocial functioning. Functioning was evaluated at four different time periods: baseline, 21 days, three months, and six months. RESULTS: A significant improvement in global functioning was found in the whole sample over the six-month period, as indicated by a reduction of FAST total score (mean +/- standard deviation) from 39.97 +/- 15.10 to 30.65 +/- 16.93 (F = 36.104, p = 0.0001). This was also evident in all areas of functioning studied. However, only 26.4% of remitted patients (n = 42) achieved functional recovery, while 79.6% of the total sample (N = 97) experienced clinical remission of acute symptoms. CONCLUSIONS: Although many patients presented syndromal recovery, only a minority of them achieved favorable functioning in multiple areas, even after specialized mental health care. Furthermore, the FAST scale was sensitive to detect minimal changes in functioning in both short (21 days) and long (6 months) periods, which may be relevant to the use of this scale in clinical trials. PMID- 22085482 TI - Do symptoms of bipolar disorder exhibit seasonal variation? A multisite prospective investigation. AB - OBJECTIVES: Evidence that symptoms of bipolar disorder (BD) vary seasonally is inconclusive. Here, a multisite prospective investigation of patients with BD was used to test the hypothesis that, on average, depressive symptoms peak in autumn/winter and hypo/manic symptoms peak in spring/summer. Secondary analyses explored gender and diagnosis [bipolar I disorder (BD-I) versus bipolar II disorder (BD-II)] effects on seasonality. METHODS: A sample of 429 patients with BD (61.6% female; 56.2% BD-I) were recruited from 12 sites across Canada. Clinician-rated measures of manic [Young Mania Rating Scale (YMRS), n = 4,753 total observations] and depression symptoms [Montgomery-Asberg Depression Rating Scale (MADRS), n = 4,691 observations] were taken at scheduled three-month visits as well as any unscheduled visits. At scheduled visits only, Hamilton Depression Rating Scale (Ham-D) assessments (n = 3,153 observations) were also made. Multi level modeling (MLM) analyses were conducted separately for the three dependent variables and three definitions of Time: calendar month, nominal season, and harmonic analysis. RESULTS: Primary analyses of the whole sample found that for manic symptoms (YMRS), neither calendar month nor nominal season were significant, and harmonic analyses found an unpredicted frequency two sinusoid, with peaks at 4th December and 4th June (p < 0.018). Secondary analyses found that this sinusoid approximately fit the YMRS data for females and those diagnosed with BD-II. For depression symptoms measured on the MADRS and Ham-D, no significant seasonal patterns were found in primary analyses of the whole sample. Secondary analyses found a significant increase in MADRS scores in November/December among females, but this pattern was not corroborated in nominal season or harmonic analyses. CONCLUSIONS: No evidence of systematic seasonal variation in symptoms was found in the sample as a whole. Primary analyses found no evidence that hypo/manic symptoms peaked in the lighter months and depressive symptoms peaked in the darker months. The present findings align with broadly negative conclusions from three earlier prospective investigations, and provide the strongest evidence to date that seasonal changes do not in fact cause coordinated variation in BD symptoms. PMID- 22085484 TI - Hippocampal alpha7 nicotinic acetylcholine receptor levels in patients with schizophrenia, bipolar disorder, or major depressive disorder. AB - BACKGROUND: The alpha7 nicotinic acetylcholine receptor (nAChR) is involved in cognitive function and synaptic plasticity. Consequently, changes in alpha7 nAChR function have been implicated in a variety of mental disorders, especially schizophrenia. However, there is little knowledge regarding the levels of the alpha7 nAChR in patients with bipolar disorder. METHODS: We performed [(125)I] bungarotoxin autoradiography to selectively visualize and measure alpha7 nAChRs on postmortem sections of the temporal lobe from patients with schizophrenia, bipolar disorder, or major depressive disorder, as well as control subjects. Radioligand binding was determined in the dentate gyrus, CA3, and CA1 subfields of the hippocampus and the perirhinal cortex. RESULTS: Bungarotoxin binding was significantly increased in the CA1 and perirhinal cortex of patients with bipolar disorder compared to control subjects, whereas in patients with schizophrenia or major depressive disorder the level of binding did not significantly differ from control subjects in any region measured. CONCLUSIONS: These data are consistent with the reported genetic associations linking the alpha7 nAChR to the pathology of bipolar disorder, and may suggest a dysfunction of alpha7 nAChR-dependent signalling in bipolar disorder. We could not reproduce the previously reported decrease in hippocampal bungarotoxin binding in schizophrenia. PMID- 22085483 TI - The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. AB - OBJECTIVES: A single nucleotide polymorphism at the CACNA1C gene (rs1006737) has been reported in genome-wide association studies to be associated with bipolar disorder (BD) with genome-wide significance. However, the neural system effects of CACNA1C that mediate the association are not known. In this study, we assessed associations between rs1006737 variation and both morphology and functional connectivity within a corticolimbic frontotemporal neural system implicated in BD. METHODS: A total of 55 European Americans were divided into two groups: a GG group homozygous for the 'G' allele (n = 30) and carriers of the high risk A allele ('A-carrier' group, AA/AG genotypes; n = 25). The subjects participated in both high-resolution structural magnetic resonance imaging (MRI) scans and functional MRI scans during emotional face-processing. Voxel-based morphometry and functional connectivity analyses were performed. RESULTS: Compared to the GG group, the A-carrier group showed significantly increased gray matter volume and reduced functional connectivity within a corticolimbic frontotemporal neural system (p < 0.05, corrected). CONCLUSION: The findings support effects of the rs1006737 variation on the frontotemporal neural system implicated in BD, both in gray matter morphology and in functional connectivity. This suggests that influence of CACNA1C variation on corticolimbic structure and function may be a mechanism contributing to the neural circuitry of BD. PMID- 22085486 TI - Dysregulated CC receptor/ligand in monocytes/macrophages from tongue squamous cell carcinoma patients is partially rectified by interferon alpha-2b. AB - In an aim to rectify dysregulated CC chemokine receptor (CCR5)/ligand (RANTES, MIP-1alpha, MIP-1beta) status of monocytes/macrophages in tongue squamous cell carcinoma (TSCC; n = 12) patients, we have tested interferon alpha2b (IFNalpha2b), a novel immunomodulator with wide use in the management of several forms of cancer. IFNalpha2b can upregulate reduced CCR5 expression and increases the suppressed secretory status of its ligands, as evidenced from in vitro studies on monocytes/macrophages from the peripheral blood of TSCC patients as well as healthy individuals. Isolated monocytes of TSCC patients (n = 5) undergoing chemotherapeutic treatment along with IFNalpha2b immunotherapy demonstrated significant upregulation in CCR5 expression and secretion of corresponding ligands. These rectifications in receptor/ligand levels are reflected in improved CCR5-dependent migration of monocytes/macrophages after IFNalpha2b treatment. The rectified chemokine profile and cellular migration translate into better tumoricidal and antigen-presenting functions of these cells. Accordingly, enhanced T-cell-mediated tumor cell killing is demonstrated upon IFNalpha2b treatment. Translating dual benefits on monocyte/macrophage functions, IFNalpha2b may emerge as a potential form of immunotherapy for TSCC patients that may be combined with standard chemotherapy for better clinical outcome. PMID- 22085487 TI - Acoustic over-exposure triggers burst firing in dorsal cochlear nucleus fusiform cells. AB - Acoustic over-exposure (AOE) triggers deafness in animals and humans and provokes auditory nerve degeneration. Weeks after exposure there is an increase in the cellular excitability within the dorsal cochlear nucleus (DCN) and this is considered as a possible neural correlate of tinnitus. The origin of this DCN hyperactivity phenomenon is still unknown but it is associated with neurons lying within the fusiform cell layer. Here we investigated changes of excitability within identified fusiform cells following AOE. Wistar rats were exposed to a loud (110 dB SPL) single tone (14.8 kHz) for 4 h. Auditory brainstem response recordings performed 3-4 days after AOE showed that the hearing thresholds were significantly elevated by about 20-30 dB SPL for frequencies above 15 kHz. Control fusiform cells fired with a regular firing pattern as assessed by the coefficient of variation of the inter-spike interval distribution of 0.19 +/- 0.11 (n = 5). Three to four days after AOE, 40% of fusiform cells exhibited irregular bursting discharge patterns (coefficient of variation of the inter spike interval distribution of 1.8 +/- 0.6, n = 5; p < 0.05). Additionally the maximal firing following step current injections was reduced in these cells (from 83 +/- 11 Hz, n = 5 in unexposed condition to 43 +/- 6 Hz, n = 5 after AOE) and this was accompanied by an increased firing gain (from 0.09 +/- 0.01 Hz/pA, n = 5 in unexposed condition to 0.56 +/- 0.25 Hz/pA, n = 5 after AOE). Current and voltage clamp recordings suggest that the presence of bursts in fusiform cells is related to a down regulation of high voltage activated potassium currents. In conclusion we showed that AOE triggers deafness at early stages and this is correlated with profound changes in the firing pattern and frequency of the DCN major output fusiform cells. The changes here described could represent the initial network imbalance prior to the emergence of tinnitus. PMID- 22085488 TI - Modulation of T cell proliferation and cytokine response by Plumbagin, extracted from Plumbago zeylanica in collagen induced arthritis. AB - BACKGROUND: The extracts of Plumbago zeylanica have been used in China and other Asian countries as folk medicine for the treatment of cancer, rheumatoid arthritis and dysmenorrhoea. Effect of Plumbagin (5-hydroxy-2-methyl-1,4 naphthoquinone) purified from Plumbago zeylanica on Con A induced T cell proliferation was studied in spleen cells from collagen induced arthritic DBA/1 mice. METHODS: The DBA/1 mice (five per each group) were immunized with 0.1 mL of collagen (emulsified in CFA) by intradermal injection at the base of the tail. On day 20, mice were given a booster dose of collagen (emulsified in IFA) through the same route. Plumbagin was given at different concentrations (3.3, 6.6, 13.3 mg/kg body weight) intraperitoneally. Control mice received olive oil alone. The Con A induced T cell proliferative responses of arthritic and Plumbagin treated mice were studied by cell culture experiments using tritiated Thymidine. In addition the cytokine levels were estimated from the in vitro spleen culture supernatants of arthritic mice primed with different concentrations of Plumbagin by ELISA. RESULTS: Plumbagin enhanced the decreased Con A induced T cell proliferation and Interleukin-2 production in arthritic mice. Moreover elevated levels of IFN- gamma were found to be decreased in Plumbagin treated spleen cell culture supernatants. Subclasses of IgG were found to be decreased by Plumbagin treatment, IgG2a reduction seems to be more prominent. CONCLUSION: The results obtained in the current study indicate that Plumbagin is very effective in the mechanism based treatment of Rheumatoid arthritis. PMID- 22085489 TI - Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): timing of maternal exposures determines target tissue response in offspring. AB - Dibenzo[def,p]chrysene (DBC) is a transplacental carcinogen in mice (15mg/kg; gestation day (GD) 17). To mimic residual exposure throughout pregnancy, dams received four smaller doses of DBC (3.75mg/kg) on GD 5, 9, 13 and 17. This regimen alleviated the previously established carcinogenic responses in the thymus, lung, and liver. However, there was a marked increase in ovarian tumors (females) and hyperplastic testes (males). [(14)C]-DBC (GD 17) dosing revealed transplacental distribution to fetal tissues at 10-fold lower concentrations than in paired maternal tissue and residual [(14)C] 3weeks post-dose. This study highlights the importance of developmental stage in susceptibility to environmental carcinogens. PMID- 22085490 TI - Insulin-like growth factor binding protein-3 inhibits migration of endometrial cancer cells. AB - Cell migration and invasion leading to metastasis is a major cause of death from endometrial cancer (EC). We have shown that the rate of EC cell migration is inversely related to the level of insulin-like growth factor protein-3 (IGFBP-3). Down-regulation of IGFBP-3 by siRNA in EC cells accelerated migration without affecting proliferation and cells displayed a more migratory phenotype, with co localization of migration-associated markers at the leading edge of cell membranes. Opposite effects were seen with either the addition of recombinant IGFBP-3 or overexpression of IGFBP-3. Cells with mutated PTEN had the highest IGFBP-3 expression and the slowest migration rates. This study demonstrates that endogenous IGFBP-3 modulates adhesion-migration dynamics in EC cells, implying that it may be important in regulating metastasis in this disease. PMID- 22085491 TI - Identification of heat shock protein 90 inhibitors to sensitize drug resistant side population tumor cells using a cell based assay platform. AB - Current cancer therapeutics are identified based on initial tumor regression screens that mostly kill differentiated tumor cells, sparing the rare cancer stem cells (CSCs). Being rare and difficult to characterize, it remains a challenge to identify compounds active against them. Side population (SP) cells identified in multiple cancer cell line panels expressing mitochondrial Cytochrome C-EGFP were evaluated for identifying possible drug candidates utilizing high-throughput imaging. We identified heat shock protein 90 inhibitors as potential agents to sensitize SP cells to anticancer drugs. Hsp90 inhibitors induced down regulation of Akt leading to proteasomal degradation of survivin and consequent mitochondrial apoptosis. A successful screening platform for identifying compounds targeting drug resistant side population cells was developed. PMID- 22085492 TI - LCH-7749944, a novel and potent p21-activated kinase 4 inhibitor, suppresses proliferation and invasion in human gastric cancer cells. AB - P21-activated kinase 4 (PAK4), a serine/threonine protein kinase, has involved in the regulation of cytoskeletal reorganization, cell proliferation, gene transcription, oncogenic transformation and cell invasion. Moreover, PAK4 overexpression, genetic amplification and mutations were detected in a variety of human tumors, which make it potential therapeutic target. In this paper we found that LCH-7749944, a novel and potent PAK4 inhibitor, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c Src/EGFR/cyclin D1 pathway. In addition, LCH-7749944 significantly inhibited the migration and invasion of human gastric cancer cells in conjunction with concomitant blockage of PAK4/LIMK1/cofilin and PAK4/MEK-1/ERK1/2/MMP2 pathways. Interestingly, LCH-7749944 also inhibited the formation of filopodia and induced cell elongation in SGC7901 cells. Importantly, LCH-7749944 caused successful inhibition of EGFR activity due to its inhibitory effect on PAK4. Taken together, these results provided novel insights into the development of PAK4 inhibitor and potential therapeutic strategies for gastric cancer. PMID- 22085494 TI - Copy number status and mutation analyses of anaplastic lymphoma kinase (ALK) gene in 90 sporadic neuroblastoma tumors. AB - Somatic and germline mutations of the anaplastic lymphoma kinase (ALK) gene were recently described in neuroblastoma (NB). In this study, we investigated the association of ALK copy number alterations with copy number status 2p24.1 amplicon harboring DEAD box polypeptide 1 (DDX1), MYCN and neuroblastoma amplified (NAG) genes in 90 primary tumors of sporadic NB cases by multiplex ligation-dependent probe amplification (MLPA). We also performed mutation analysis of ALK gene by directly sequencing the exons 20-28 which cover the region that encodes juxtamembrane and kinase domains. A total of 39 (43.3%) NB cases revealed copy numbers alterations of ALK gene. There was highly significant association of ALK copy number gains with gains of one or more of the genes at 2p24.1 (DDX1, MYCN or NAG) in MYCN unamplified tumors (P<0.000). In addition, 15 of 17 MYCN amplified cases (88.2%) had aberrant ALK status. Solitary gain of ALK with normal copy number status of all other genes was observed only in one case. DNA sequencing of exons 20-28 of ALK revealed two different nucleotide changes in three cases leading to amino acid substitutions of F1245V and R1275Q in tyrosine kinase domain. In conclusion, the frequency of ALK mutations in NB is low and solitary copy number change of it is rarely observed. PMID- 22085493 TI - Bortezomib enhances radiation-induced apoptosis in solid tumors by inhibiting CIP2A. AB - Previously, we demonstrated that cancerous inhibitor of protein phosphatase 2A (CIP2A) mediates bortezomib-induced apoptosis in hepatocellular carcinoma cells. Herein, we report that bortezomib sensitizes solid tumor cells to radiation induced apoptosis. Treatment with a combination of bortezomib and radiation downregulated CIP2A in a dose-dependent manner in solid tumor cells. Knockdown of CIP2A enhanced radiation-induced apoptosis in cancer cells, and ectopic expression of CIP2A in cancer cells abolished radiation-induced apoptosis. Finally, our in vivo data showed that bortezomib and radiation combination treatment decreased tumor growth significantly. Thus, bortezomib sensitized solid tumor cells to radiation through the inhibition of CIP2A. PMID- 22085495 TI - Species-specific toxicity of troglitazone on rats and human by gel entrapped hepatocytes. AB - Troglitazone, despite passing preclinical trials on animals, was shortly withdrawn from market due to its severe hepatotoxicity in clinic. As rat hepatocyte monolayer consistently showed sensitive troglitazone toxicity as human hepatocyte monolayer in contrast to the species-specific toxicity in vivo, this paper utilized both hepatocytes in three-dimensional culture of gel entrapment to reflect the species difference on hepatotoxicity. Rat hepatocytes in gel entrapment did not show obvious cellular damage even under a long-term exposure for 21 days while gel entrapped human hepatocytes significantly displayed oxidative stress, steatosis, mitochondrial damage and cell death at a short exposure for 4 days. As a result, the detected species-specific toxicity of troglitazone between gel entrapped rat and human hepatocytes consisted well with the situation in vivo but was in a sharp contrast to the performance of two hepatocytes by monolayer culture. Such contradictory toxicity of rat hepatocytes between monolayer and gel entrapment culture could be explained by the fact that troglitazone was cleared more rapidly in gel entrapment than in monolayer culture. Similarly, the differential clearance of troglitazone in rat and human might also explain its species-specific toxicity. Therefore, gel entrapment of hepatocytes might serve as a platform for evaluation of drug toxicity at early stage of drug development by reducing costs, increasing the likelihood of clinical success and limiting human exposure to unsafe drugs. PMID- 22085496 TI - Strain-induced yielding in bubble clusters. AB - We study how shearing clusters of two or four bubbles induces bubble separation or topological rearrangement. The critical deformation at which this yielding occurs is measured as a function of shear rate, liquid composition, and liquid content in the cluster. We establish a geometrical yield criterion in the quasistatic case on the basis of these experimental data as well as simulations. In the dynamic regime, the deformation where the cluster yields increases with the strain rate, and we derive a scaling law describing this phenomenon based on the dynamical inertial rupture of the liquid meniscus linking the two bubbles. Our experiments show that the same scaling law applies to two- and four-bubble clusters. PMID- 22085497 TI - A pair of orthologs of a leucine-rich repeat receptor kinase-like disease resistance gene family regulates rice response to raised temperature. AB - BACKGROUND: Rice Xa3/Xa26 disease-resistance gene encodes a leucine-rich repeat (LRR) receptor kinase-type protein against Xanthomonas oryzae pv. oryzae (Xoo) and belongs to a multigene family. However, the functions of most genes in this family are unknown. RESULTS: Here we report that two orthologs of this family, the NRKe from rice variety Nipponbare and 9RKe from variety 93-11 at the RKe locus, have similar functions although they encode different proteins. This pair of orthologs could not mediate resistance to Xoo, but they were transcriptionally induced by raised temperature. Transcriptional activation of NRKe or 9RKe resulted in the formation of temperature-sensitive lesion mimics, which were spots of dead cells associated with accumulation of superoxides, in different organs of the transgenic plants. These plants were more sensitive to high temperature shock than wild-type controls. Transgenic plants carrying a chimeric protein consisting of the LRR domain of NRKe and the kinase domain of Xa3/Xa26 developed the same lesion mimics as the NRKe-transgenic plants, whereas transgenic plants carrying another chimeric protein consisting of the LRR domain of Xa3/Xa26 and the kinase domain of NRKe were free of lesion mimic. All the transgenic plants carrying a chimeric protein were susceptible to Xoo. CONCLUSION: These results suggest that the RKe locus is involved in rice response to raised temperature. The LRR domain of RKe protein appears to be important to sense increased temperature. The RKe-involved temperature-related pathway and Xa3/Xa26-mediated disease-resistance pathway may partially overlap. PMID- 22085498 TI - E-cadherin cell-cell communication in melanogenesis and during development of malignant melanoma. AB - Cell-cell communication is necessary for the crosstalk between cells that constitute multicellular organisms and is essential for cells to coordinate their physiological behavior to create cohesive tissues. Cellular crosstalk is not only controlled by molecules, like growth factors, hormones, ions and G-proteins, etc. but also by cell-cell contacts. These contacts are essential for intercellular communication and are involved in survival, apoptosis, proliferation, differentiation and homeostasis of entire tissues. In polarized epithelia of vertebrates, the adherent junction is part of the tripartite junctional complex that is localized at the juxtaluminal region, which includes tight junctions (including claudins, occludins, and zonula occludens proteins), desmosomal junctions (including desmogleins), and adherent junctions. In focus of the manuscript are adherent molecules of the cadherin superfamily of the skin. In the normal epidermis, melanocytes and keratinocytes are mostly connected via E cadherin, P-cadherin and H-cadherin [1-3]. Melanocytes that reside in the basal layer of the epidermis predominantly contain E-cadherin and H-cadherin, whereas those that reside in the hair follicles are rich in P-cadherin [2]. The regulation and role of E-cadherin during melanoma development will be the focus of this review. PMID- 22085499 TI - Cellular and molecular effects of vitamin D on carcinogenesis. AB - Epidemiologic data suggest that the incidence and severity of many types of cancer inversely correlates with indices of vitamin D status. The vitamin D receptor (VDR) is highly expressed in epithelial cells at risk for carcinogenesis including those resident in skin, breast, prostate and colon, providing a direct molecular link by which vitamin D status impacts on carcinogenesis. Consistent with this concept, activation of VDR by its ligand 1,25-dihydroxyvitamin D (1,25D) triggers comprehensive genomic changes in epithelial cells that contribute to maintenance of the differentiated phenotype, resistance to cellular stresses and protection of the genome. Many epithelial cells also express the vitamin D metabolizing enzyme CYP27B1 which enables autocrine generation of 1,25D from the circulating vitamin D metabolite 25-hydroxyvitamin D (25D), critically linking overall vitamin D status with cellular anti-tumor actions. Furthermore, pre-clinical studies in animal models has demonstrated that dietary supplementation with vitamin D or chronic treatment with VDR agonists decreases tumor development in skin, colon, prostate and breast. Conversely, deletion of the VDR gene in mice alters the balance between proliferation and apoptosis, increases oxidative DNA damage, and enhances susceptibility to carcinogenesis in these tissues. Because VDR expression is retained in many human tumors, vitamin D status may be an important modulator of cancer progression in persons living with cancer. Collectively, these observations have reinforced the need to further define the molecular actions of the VDR and the human requirement for vitamin D in relation to cancer development and progression. PMID- 22085500 TI - Vitamin D, multiple sclerosis and inflammatory bowel disease. AB - It has now been more than 20years since the vitamin D receptor was identified in cells of the immune system. The immune system has now been established as an important target of vitamin D. Vitamin D receptor knockout and vitamin D deficient mice have a surplus of effector T cells that have been implicated in the pathology of multiple sclerosis (MS) and inflammatory bowel disease (IBD). The active form of vitamin D directly and indirectly suppresses the function of these pathogenic T cells while inducing several regulatory T cells that suppress MS and IBD development. There is reason to believe that vitamin D could be an environmental factor that may play a role in the development of these immune mediated diseases in the clinic but at present there has not been a causal relationship established. Nonetheless, current evidence suggests that improving vitamin D status and/or using vitamin D receptor agonists may be useful in MS and IBD. PMID- 22085501 TI - S1 pocket fingerprints of human and bacterial methionine aminopeptidases determined using fluorogenic libraries of substrates and phosphorus based inhibitors. AB - Methionyl aminopeptidases (MetAPs) are metallo-dependent proteases responsible for removing of N-terminal methionine residue of peptides and proteins during protein maturation and activation. In this report we use a comprehensive strategy to screen the substrate specificity of three methionyl aminopeptidases: Homo sapiens MetAP-1, Homo sapiens MetAP-2 and Escherichia coli MetAP-1. By utilizing a 65-membered fluorogenic substrate library consisting of natural and unnatural amino acids we established detailed substrate preferences of each enzyme in the S1 pocket. Our results show that this pocket is highly conserved for all investigated MetAPs, very stringent for methionine, and that several unnatural amino acids with methionine-like characteristics were also well hydrolyzed by MetAPs. The substrate-derived results were verified using several phosphonate and phosphinate-based inhibitors. PMID- 22085502 TI - [A man with pain and weakness in his legs]. AB - A 75-year-old man came to the clinic because of pain and weakness in his legs. He had fallen a year earlier. The pain and weakness were caused by a bilateral rupture of the tendon of the M. rectus femoris. PMID- 22085504 TI - Psoriasiform disorders with joint symptoms. AB - We present a 49-year-old man seen at the dermatology outpatient department with a 3-year history of painful swollen digits of hands and feet. On enquiry he reported dysuria. On examination we saw extensive swelling of the digits, keratosis of the nails, and some psoriasiform skin lesions on the soles of the feet. The differential diagnosis included acrodermatitis continua suppurativa, reactive arthritis and psoriatic arthritis. Radiographic imaging revealed the presence of arthritis. Testing proved negative for rheumatoid factor and positive for HLA-B27 making spondyloarthropathy the most likely diagnosis, either in the form of reactive arthritis or psoriatic arthritis. The patient was treated with combination therapy of doxycycline, methotrexate and folic acid. Because of insufficient response to therapy, the methotrexate dose was raised and eventually etanercept was added. During the last visit to the outpatient clinic, the patient still showed insufficient response to therapy. PMID- 22085505 TI - [Unexpected back pain in the elderly ankylosing spondylitis patient]. AB - A 63-year-old man with ankylosing spondylitis (AS) presented with persistent pain in his back after minor trauma. Radiographs revealed no acute pathology. Six weeks later an MRI scan was performed which showed a vertebral fracture at level Tiii with kyphotic deformity. Another 63-year-old male AS patient presented with back pain after minor trauma 10 days before presentation. At plain radiology a vertebral fracture of Tx was discovered. A third patient, an 83-year-old male AS patient complained about back pain after minor trauma; CT imaging revealed a Tx vertebral fracture. All three patients underwent surgical fixation and were discharged without major complications. In principle, an older patient with an established AS complaining of back pain must be regarded as having a fracture of the vertebral column until the contrary is proven, even in the absence of any recent history of trauma. This strategy can prevent major complication in these patients. PMID- 22085506 TI - [Early recognition of rheumatoid arthritis]. AB - Target to treat within the first 12 weeks. The rheumatoid arthritis (RA) disease process may be modulated best in the very early phase of the disease, therefore the period of the first 12 weeks of the disease is called the "window of opportunity". Patients in whom treatment is started within 12 weeks of onset of symptoms develop less severe joint damage and have a better chance of remission. At present only 31% of Dutch new RA patients are assessed by a rheumatologist within 12 weeks of symptom onset. Arthritis is identified by joint palpation; in order to detect subtle arthritis of minor joints, experience in carrying out this joint examination is required. In order to distinguish patients with early RA from other patients with recent onset arthritis, several prediction models have been developed. Early recognition of arthritis and RA is mandatory for early treatment of RA and improvement of the prospects of RA patients. PMID- 22085508 TI - [The multidisciplinary practice guideline "The responsible use of biologicals"]. AB - A multidisciplinary working group has developed a practice guideline containing various recommendations on the responsible and efficient use of biologicals. These biologicals include both soluble immune-receptor proteins and monoclonal antibodies that are aimed at immune mediators, receptors or cells. They are produced by biotechnology. Biologicals are used to treat patients with immune mediated inflammatory disorders (IMIDs) such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, juvenile idiopathic arthritis (JIA), psoriasis, ulcerative colitis, Crohn's disease, uveitis and sarcoidosis. This article summarises the most important recommendations contained in the practice guideline. The practice guideline is intended for members of the medical profession in addition to patients, who are considering, or are already, using biologicals. PMID- 22085509 TI - [Wenckebach and his rhythm]. AB - Karel Frederik Wenckebach (1864-1940) showed an aptitude for research even as a medical student in Utrecht. After graduation and a thesis on the bursa of Fabricius he worked as an assistant in the physiological laboratory. Following a stint as general practitioner in a mining community (1891-1896) he returned to Utrecht, where he could combine his practice with physiological studies, especially disturbances of the heart rhythm. In 1899, with no other recording instruments than a sphygmomanometer for tracing the radial pulse and a tuning fork for chronometry, he described the 'rhythmic arrhythmia' phenomenon: a missed beat after a given number of regular beats (mostly between three and six), followed by an intermission shorter than the interval between two regular beats. The Wenckebach rhythm is now also known as type I second-degree atrioventricular block. Wenckebach subsequently became a professor of medicine in Groningen (1901), Strasbourg (1911) and Vienna (1914-1929). PMID- 22085510 TI - [Exercise therapy in hip or knee osteoarthritis]. AB - "Exercise is medicine": exercise therapy reduces pain and activity limitations in osteoarthritis of the knee and is likely to have the same effects in osteoarthritis of the hip. Further research into exercise therapy is needed, since disease-modifying drugs are not available, pain medication can cause side effects, and surgical interventions are preferably applied in an advanced stage of disease. Classical exercise therapy is aimed at improving muscle strength, aerobic capacity, range of joint motion, and training of walking and activities of daily living. New modalities of targeted exercise therapy are currently being developed, aimed at the correction of low levels of activity and to correct instability of the knee. Weight loss, preferably combined with exercise therapy, reduces pain and activity limitations in osteoarthritis patients who are overweight. Modalities of exercise therapy adapted to comorbid conditions are currently being developed. PMID- 22085511 TI - [From splint to smart syringe: the changing perspective of rheumatology]. AB - Over the course of the past 30 years the outlook for patients with rheumatic arthritis (RA) has changed substantially. The careful "wait-and-see" attitude of rheumatologists of the past has been replaced by early and intensive intervention in patients with early RA. These days it is possible to bring about remission in half of all patients with, among others, the new medicines-- the "biologicals". Auto-antibodies are now detectable in the pre-clinical phase of RA; this means that in the future it will be possible to trace people with a raised risk of developing RA. PMID- 22085512 TI - [Determining cardiovascular risk in patients with rheumatoid arthritis: waiting for trial outcomes is not recommended]. AB - Cardiovascular risk management is clearly indicated in patients with rheumatoid arthritis (RA) today because this risk is comparable to patients with diabetes. Although formal evidence of cardiovascular endpoint trials with statins and/or antihypertensives is lacking in patients with RA, there are no indications that these drugs will have limited effect. In contrast, there is accumulating evidence as to the efficacy of the use of these drugs in RA that is at least comparable to their effects in the general population. All patients with RA should therefore receive cardiovascular risk-management therapy aimed at powerful suppression of the chronic inflammatory process as well as treatment with statins and/or antihypertensives, if indicated. Obviously, monitoring in the clinical setting is necessary to document if such therapy does indeed reduce cardiovascular disease in patients with RA. PMID- 22085514 TI - [Employee participation by patients with rheumatoid arthritis and spondylarthritis. Biologicals may have an effect on the loss of productivity]. AB - Rheumatoid arthritis (RA) and the various types of spondylarthritis (SpA) contribute significantly to employee disability. Each of these inflammatory diseases has a great impact on physical and mental health, thereby restricting one's ability to participate in one's social roles. This may result in decreased productivity during working hours (sickness presenteeism), absenteeism and eventually, disablement, with financial consequences for the patient as well as society. By incorporating biologicals into treatment strategies, the health of patients with RA and SpA can be better regulated; however, the cost of such treatment has risen considerably. There are indications that part of these high treatment expenditures can be regained by improved employee productivity of these patients. PMID- 22085517 TI - [The patient with arthritis: care by both general practitioners and rheumatologists]. AB - Early aggressive treatment of rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs such as TNF inhibitors prevents joint damage and improves the quality of life. There is increasing insight regarding the cardiovascular risks of patients suffering from RA or gout. These aspects and others are considered in this paper with respect to early diagnosis, treatment and prognosis of patients with arthritis, in particular RA or gout. In the Netherlands approximately 8900 general practitioners (GPs) and 230 rheumatologists, working in different settings (primary care and hospitals), are together responsible for the care of patients with arthritis. They must communicate and co-operate at a national, regional and local level to organize this care--the aim being to reach mutual agreement regarding the responsibility for each part of the diagnosis and management at each stage of the disease. PMID- 22085518 TI - [Determining cardiovascular risk in patients with rheumatoid arthritis: prove the efficacy of interventions first]. AB - In the multidisciplinary Dutch guideline on Cardiovascular Risk Management (revision 2011) the recommendation for preventive treatment of elevated risks of cardiovascular disease in patients with arthritis lacks a trial-based justification. This section should therefore be removed. Introduction of clinical guidelines with recommendations justified by evidence of an unacceptably low grade is a growing international tendency that should be stopped. PMID- 22085519 TI - [Tailored therapy for rheumatic disease within reach]. AB - Personalised medicine has the potential to increase therapeutic effectiveness, reduce side effects and lower cost. This approach has recently taken off in oncology where different malignancies may be treated with specific drugs based on genetic biomarkers or other tumour characteristics. This type of tailored therapy could also be developed for immune-mediated inflammatory disease, for which rheumatoid arthritis (RA) may serve as a prototype. While novel treatments are able to halt or even prevent disease progression, not all RA patients respond, and stratification of patient groups is needed. The identification of biomarkers predictive of the clinical response to specific treatments in subsets of patients may soon become reality in a variety of diseases. PMID- 22085520 TI - [The recognition of patients with spondyloarthritis. New classification criteria]. AB - Spondyloarthritis (SpA) is an umbrella term for a group of rheumatic diseases characterised by inflammation of the sacroiliac (SI) joints and vertebral column; today, differentiation is made between axial SpA and peripheral SpA. Ankylosing spondylitis (Bechterew's disease) is the most typical form of axial SpA whereby sacroiliitis can be found on X-rays of the SI joints. Axial SpA can, however, also be present without radiographic evidence of sacroiliitis. A range of SpA related symptoms can also manifest themselves outside the musculoskeletal system, for example, uveitis, psoriasis and inflammatory intestinal diseases. Tumour necrosis factor (TNF)-alpha inhibitors play an important role in the treatment of SpA. New classification criteria have recently been established in which MRI of the SI joints and the presence of the HLA-B27 tissue antigen are key. Axial and peripheral SpA should be recognized early in order to be able to successfully treat these conditions. PMID- 22085521 TI - [Self-management in anticoagulant therapy--implications for the future?]. AB - Recent meta-analysis has demonstrated that self-management in oral anticoagulant therapy results in fewer thromboembolic complications and a decrease in mortality in comparison to conventional treatment, while the number of bleeding complications remains unchanged. We discuss the importance of these findings for the situation in the Netherlands with its specialized anticoagulation clinics and the possible consequences for the introduction of new anticoagulants like dabigatran and rivaroxaban. PMID- 22085522 TI - [Bicycle spoke-related injuries in children: emphasise prevention]. AB - Three children, a 6-year-old boy and two girls aged 5 and 4 years, were seen at an emergency department due to distal lower-leg injuries sustained from the spokes of bicycle wheels. All three patients had been passengers on rear carrying seats of moving bicycles. Only the third bicyclist had used a special child safety seat. The second girl had drawn her foot up from underneath a strap and suffered a tibial fracture later treated with an osteosynthetic plate. The other two patients recovered after conservative casting treatment. Bicycle spoke related injuries are sustained when the foot or lower limb makes contact with the spokes of a bicycle wheel and usually by children who are bicycle passengers. In the Netherlands, approximately 4600 children are seen at emergency departments with such injuries each year. Bicycle spoke-related accidents can cause severe damage that can result in lengthy recovery periods. Not only physical complications but also psychological ones can occur. The latter are often overlooked but do deserve proper treatment. The physician treating a spoke related injury is in a good position to advice parents as to preventive measures, particularly on the use of special child safety seats. PMID- 22085523 TI - Cook It Up! A community-based cooking program for at-risk youth: overview of a food literacy intervention. AB - BACKGROUND: In Canada, there are limited occasions for youth, and especially at risk youth, to participate in cooking programs. The paucity of these programs creates an opportunity for youth-focused cooking programs to be developed, implemented, and evaluated with the goal of providing invaluable life skills and food literacy to this potentially vulnerable group. Thus, an 18-month community based cooking program for at-risk youth was planned and implemented to improve the development and progression of cooking skills and food literacy. FINDINGS: This paper provides an overview of the rationale for and implementation of a cooking skills intervention for at-risk youth. The manuscript provides information about the process of planning and implementing the intervention as well as the evaluation plan. Results of the intervention will be presented elsewhere. Objectives of the intervention included the provision of applied food literacy and cooking skills education taught by local chefs and a Registered Dietitian, and augmented with fieldtrips to community farms to foster an appreciation and understanding of food, from 'gate to plate'. Eight at-risk youth (five girls and three boys, mean age = 14.6) completed the intervention as of November 2010. Pre-test cooking skills assessments were completed for all participants and post-test cooking skills assessments were completed for five of eight participants. Post intervention, five of eight participants completed in depth interviews about their experience. DISCUSSION: The Cook It Up! program can provide an effective template for other agencies and researchers to utilize for enhancing existing programs or to create new applied cooking programs for relevant vulnerable populations. There is also a continued need for applied research in this area to reverse the erosion of cooking skills in Canadian society. PMID- 22085524 TI - POPISK: T-cell reactivity prediction using support vector machines and string kernels. AB - BACKGROUND: Accurate prediction of peptide immunogenicity and characterization of relation between peptide sequences and peptide immunogenicity will be greatly helpful for vaccine designs and understanding of the immune system. In contrast to the prediction of antigen processing and presentation pathway, the prediction of subsequent T-cell reactivity is a much harder topic. Previous studies of identifying T-cell receptor (TCR) recognition positions were based on small-scale analyses using only a few peptides and concluded different recognition positions such as positions 4, 6 and 8 of peptides with length 9. Large-scale analyses are necessary to better characterize the effect of peptide sequence variations on T cell reactivity and design predictors of a peptide's T-cell reactivity (and thus immunogenicity). The identification and characterization of important positions influencing T-cell reactivity will provide insights into the underlying mechanism of immunogenicity. RESULTS: This work establishes a large dataset by collecting immunogenicity data from three major immunology databases. In order to consider the effect of MHC restriction, peptides are classified by their associated MHC alleles. Subsequently, a computational method (named POPISK) using support vector machine with a weighted degree string kernel is proposed to predict T-cell reactivity and identify important recognition positions. POPISK yields a mean 10 fold cross-validation accuracy of 68% in predicting T-cell reactivity of HLA-A2 binding peptides. POPISK is capable of predicting immunogenicity with scores that can also correctly predict the change in T-cell reactivity related to point mutations in epitopes reported in previous studies using crystal structures. Thorough analyses of the prediction results identify the important positions 4, 6, 8 and 9, and yield insights into the molecular basis for TCR recognition. Finally, we relate this finding to physicochemical properties and structural features of the MHC-peptide-TCR interaction. CONCLUSIONS: A computational method POPISK is proposed to predict immunogenicity with scores which are useful for predicting immunogenicity changes made by single-residue modifications. The web server of POPISK is freely available at http://iclab.life.nctu.edu.tw/POPISK. PMID- 22085525 TI - A brief report on perceptions of alcohol and society among Scottish medical students. AB - AIMS: To assess perceptions on alcohol misuse and addiction among medical students prior to in-depth training in order to determine areas of the curriculum that need to be reshaped or focused on. METHODS: A questionnaire assessment of first- and second-year medical students' perceptions of alcohol misuse. RESULTS: Students had some misconceptions about current alcohol misuse rates, including a perception that addiction is common among health professionals, that the under 25s had the fastest increasing rate of alcohol addiction and that British women had a more rapidly increasing rate of alcohol addiction than British men. CONCLUSION: Encouragingly, students overwhelmingly felt that alcohol addiction was something to which they could make a difference. It highlights that early education about alcohol misuse is important in terms of teaching students how to recognize hazardous and harmful drinkers and how to manage them. PMID- 22085526 TI - East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians. AB - Prostate cancer is the most prevalent cancer in males in Western countries. The reported incidence in Asia is much lower than that in African Americans and European Caucasians. Although the lack of systematic prostate cancer screening system in Asian countries explains part of the difference, this alone cannot fully explain the lower incidence in Asian immigrants in the United States and west-European countries compared to the black and non-Hispanic white in those countries, nor the somewhat better prognosis in Asian immigrants with prostate cancer in the United States. Soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer. Prostate-specific antigen(PSA) is the only established and routinely implemented clinical biomarker for prostate cancer detection and disease status. Other biomarkers, such as urinary prostate cancer antigen 3 RNA, may increase accuracy of prostate cancer screening compared to PSA alone. Several susceptible loci have been identified in genetic linkage analyses in populations of countries in the West, and approximately 30 genetic polymorphisms have been reported to modestly increase the prostate cancer risk in genome-wide association studies. Most of the identified polymorphisms are reproducible regardless of ethnicity. Somatic mutations in the genomes of prostate tumors have been repeatedly reported to include deletion and gain of the 8p and 8q chromosomal regions, respectively; epigenetic gene silencing of glutathione S-transferase Pi(GSTP1); as well as mutations in androgen receptor gene. However, the molecular mechanisms underlying carcinogenesis, aggressiveness, and prognosis of prostate cancer remain largely unknown. Gene-gene and/or gene-environment interactions still need to be learned. In this review, the differences in PSA screening practice, reported incidence and prognosis of prostate cancer, and genetic factors between the populations in East and West factors are discussed. PMID- 22085527 TI - Schwannoma of the conus medullaris: a rare case. AB - Intradural schwannoma of the conus medullaris is a rare form of spinal neoplasm, which commonly occurs in the lumbar region. Conus medullaris level is unusual for schwannomas. A 49-year-old woman presented with chronic sciatica, mild bladder dysfunction, and paresthesia in the buttocks. Magnetic resonance imaging of the spine showed a mass lesion in the conus medullaris region with nerve compression. The tumor was completely resected and diagnosed histologically as schwannoma. The patient recovered after surgery. Clinical and radiologic features of this rare tumor are reviewed and are accompanied by literature findings. PMID- 22085528 TI - miR-124 suppresses multiple steps of breast cancer metastasis by targeting a cohort of pro-metastatic genes in vitro. AB - Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment. PMID- 22085529 TI - Both mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (ERK) 1/2 and phosphatidylinositide-3-OH kinase (PI3K)/Akt pathways regulate activation of E-twenty-six (ETS)-like transcription factor 1 (Elk-1) in U138 glioblastoma cells. AB - Epidermal growth factor (EGF) and its receptor (EGFR) have been shown to play a significant role in the pathogenesis of glioblastoma. In our study, the EGFR was stimulated with EGF in human U138 glioblastoma cells. We show that the activated mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (ERK) 1/2 pathway phosphorylated the E twenty-six (ETS)-like transcription factor 1 (Elk-1) mainly at serine 383 residue. Mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, UO126 and ERK inhibitor II, FR180204 blocked the Elk-1 phosphorylation and activation. The phosphatidylinositide-3-OH kinase (PI3K)/Akt pathway was also involved in the Elk-1 activation. Activation of the Elk-1 led to an increased survival and a proliferative response with the EGF stimulation in the U138 glioblastoma cells. Knocking-down the Elk-1 using an RNA interference technique caused a decrease in survival of the unstimulated U138 glioblastoma cells and also decreased the proliferative response to the EGF stimulation. The Elk-1 transcription factor was important for the survival and proliferation of U138 glioblastoma cells upon the stimulation of EGFR with EGF. The MAPK/ERK1/2 and PI3K/Akt pathways regulated this response via activation of the Elk-1 transcription factor. The Elk-1 may be one of the convergence points for pathways located downstream of EGFR in glioblastoma cells. Utilization of the Elk-1 as a therapeutic target may lead to a novel strategy in treatment of glioblastoma. PMID- 22085530 TI - Oxaloacetate: a novel neuroprotective for acute ischemic stroke. AB - It is well established that glutamate acts as an important mediator of neuronal degeneration during cerebral ischemia. Different kind of glutamate antagonists have been used to reduce the deleterious effects of glutamate. However, their preclinical success failed to translate into practical treatments. Far from the classical use of glutamate antagonists employed so far, the systemic administration of oxaloacetate represents a novel neuroprotective strategy to minimize the deleterious effect of glutamate in the brain tissue after ischemic stroke. The neuroprotective effect of oxaloacetate is based on the capacity of this molecule to reduce the brain and blood glutamate levels as a result of the activation of the blood-resident enzyme glutamate-oxaloacetate transaminase. Here we review the recent experimental and clinical results where it is demonstrated the potential applicability of oxaloacetate as a novel and powerful neuroprotective treatment against ischemic stroke. PMID- 22085531 TI - A butyrolactone derivative suppressed lipopolysaccharide-induced autophagic injury through inhibiting the autoregulatory loop of p8 and p53 in vascular endothelial cells. AB - Lipopolysaccharide (LPS)-induced vascular endothelial cell (VEC) dysfunction is an important contributing factor in vascular diseases. Recently, we found that LPS impaired VEC by inducing autophagy. Our previous researches showed that a butyrolactone derivative, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H) one (3BDO) selectively protected VEC function. The objective of the present study is to investigate whether and how 3BDO inhibits LPS-induced VEC autophagic injury. Our results showed that LPS induced autophagy and led to increase of reactive oxygen species (ROS) and decrease of mitochondrial membrane potential (MMP) in Human umbilical vein vascular endothelial cells (HUVECs). Furthermore, LPS significantly increased p8 and p53 protein levels and the nuclear translocation of p53. All of these effects of LPS on HUVECs were strongly inhibited by 3BDO. Importantly, the ROS scavenger N-acetylcysteine (NAC) could inhibited LPS-induced autophagy and knockdown of p8 by RNA interference inhibited the autophagy, p53 protein level increase, the translocation of p53 into nuclei and the ROS level increase induced by LPS in HUVECs. The data suggested that 3BDO inhibited LPS-induced autophagy in HUVECs through inhibiting the ROS overproduction, the increase of p8 and p53 expression and the nuclear translocation of p53. Our findings provide a potential tool for understanding the mechanism underlying LPS-induced autophagy in HUVECs and open the door to a novel therapeutic drug for LPS-induced vascular diseases. PMID- 22085532 TI - Nanoscale chemical and structural study of Co-based FEBID structures by STEM-EELS and HRTEM. AB - Nanolithography techniques in a scanning electron microscope/focused ion beam are very attractive tools for a number of synthetic processes, including the fabrication of ferromagnetic nano-objects, with potential applications in magnetic storage or magnetic sensing. One of the most versatile techniques is the focused electron beam induced deposition, an efficient method for the production of magnetic structures highly resolved at the nanometric scale. In this work, this method has been applied to the controlled growth of magnetic nanostructures using Co2(CO)8. The chemical and structural properties of these deposits have been studied by electron energy loss spectroscopy and high-resolution transmission electron microscopy at the nanometric scale. The obtained results allow us to correlate the chemical and structural properties with the functionality of these magnetic nanostructures. PMID- 22085533 TI - Hyaluronan serum concentrations are elevated in critically ill patients and associated with disease severity. AB - OBJECTIVES: The matrix protein hyaluronic acid (HA, hyaluronan) has possibly additional immune-regulatory functions in inflammation. We aimed at evaluating serum HA concentrations in critically ill patients. DESIGN AND METHODS: We analyzed serum HA levels in 164 critically ill patients at a medical ICU and 61 healthy controls, with respect to organ dysfunction, systemic inflammation and mortality. RESULTS: Hyaluronan serum concentrations upon admission to ICU were significantly elevated in critically ill patients compared to healthy controls, with the highest levels in patients with pre-existing liver cirrhosis or sepsis. HA levels were closely correlated with biomarkers of hepatic and renal function, systemic inflammation, demand of treatment measures and clinical scores of disease severity, but could not predict risk of mortality. CONCLUSIONS: Measurement of serum HA may supplement the assessment of disease severity in ICU patients. Our data suggest that HA might have implications in the pathogenesis of critical illness and sepsis. PMID- 22085534 TI - Spinal muscular atrophy: clinical validation of a single-tube multiplex real time PCR assay for determination of SMN1 and SMN2 copy numbers. AB - OBJECTIVES: To describe and validate a new protocol for molecular diagnosis of spinal muscular atrophy (SMA), a frequent neuromuscular disease of childhood. DESIGN AND METHODS: SMA is caused in most cases by homozygous deletion of the SMN1 gene. We describe a triplex quantitative real-time PCR method in which fragments of SMN1, SMN2 (a nearly-identical neighboring gene with markedly reduced function) and of a control gene, CFTR, are amplified in the same tube. RESULTS: We validated this method in three ways. First, testing the same samples ten times yielded CV values <4.6%. Second, in 104 previously-genotyped individuals, SMN copy numbers identical to those of the previously-determined genotype was unambiguously obtained in all cases. Finally, results using the technique in practice are described and analyzed for reproducibility of amplification efficiency and for inter-run variability. CONCLUSIONS: In over 1200 samples, this technique has proven accurate, fast, economical and reproducible. PMID- 22085535 TI - Enhancer-driven chromatin interactions during development promote escape from silencing by a long non-coding RNA. AB - BACKGROUND: Gene regulation in eukaryotes is a complex process entailing the establishment of transcriptionally silent chromatin domains interspersed with regions of active transcription. Imprinted domains consist of clusters of genes, some of which exhibit parent-of-origin dependent monoallelic expression, while others are biallelic. The Kcnq1 imprinted domain illustrates the complexities of long-range regulation that coexists with local exceptions. A paternally expressed repressive non-coding RNA, Kcnq1ot1, regulates a domain of up to 750 kb, encompassing 14 genes. We study how the Kcnq1 gene, initially silenced by Kcnq1ot1, undergoes tissue-specific escape from imprinting during development. Specifically, we uncover the role of chromosome conformation during these events. RESULTS: We show that Kcnq1 transitions from monoallelic to biallelic expression during mid gestation in the developing heart. This transition is not associated with the loss of methylation on the Kcnq1 promoter. However, by exploiting chromosome conformation capture (3C) technology, we find tissue-specific and stage-specific chromatin loops between the Kcnq1 promoter and newly identified DNA regulatory elements. These regulatory elements showed in vitro activity in a luciferase assay and in vivo activity in transgenic embryos. CONCLUSIONS: By exploring the spatial organization of the Kcnq1 locus, our results reveal a novel mechanism by which local activation of genes can override the regional silencing effects of non-coding RNAs. PMID- 22085536 TI - Knowledge, attitudes and practice survey about antimicrobial resistance and prescribing among physicians in a hospital setting in Lima, Peru. AB - BACKGROUND: Misuse of antimicrobials (AMs) and antimicrobial resistance (AMR) are global concerns. The present study evaluated knowledge, attitudes and practices about AMR and AM prescribing among medical doctors in two large public hospitals in Lima, Peru, a middle-income country. METHODS: Cross-sectional study using a self-administered questionnaire RESULTS: A total of 256 participants completed the questionnaire (response rate 82%). Theoretical knowledge was good (mean score of 6 +/- 1.3 on 7 questions) in contrast to poor awareness (< 33%) of local AMR rates of key-pathogens. Participants strongly agreed that AMR is a problem worldwide (70%) and in Peru (65%), but less in their own practice (22%). AM overuse was perceived both for the community (96%) and the hospital settings (90%). Patients' pressure to prescribing AMs was considered as contributing to AM overuse in the community (72%) more than in the hospital setting (50%). Confidence among AM prescribing was higher among attending physicians (82%) compared to residents (30%, p < 0.001%). Sources of information considered as very useful/useful included pocket-based AM prescribing guidelines (69%) and internet sources (62%). Fifty seven percent of participants regarded AMs in their hospitals to be of poor quality. Participants requested more AM prescribing educational programs (96%) and local AM guidelines (92%). CONCLUSIONS: This survey revealed topics to address during future AM prescribing interventions such as dissemination of information about local AMR rates, promoting confidence in the quality of locally available AMs, redaction and dissemination of local AM guidelines and addressing the general public, and exploring the possibilities of internet-based training. PMID- 22085537 TI - Analytical determination of apparent stability constants using a copper ion selective electrode. AB - Copper(II) complexes of di-, tri- and tetra peptides with previously published protonation constants were re-investigated using pH and copper ion selective electrode (ISE) potentiometry in conjunction with a modified version of HYPERQUAD computer program. The purpose was to demonstrate the suitability of the ISE approach for the determination of apparent stability constants for copper(II) complexes with ligands for which proton stability constants were not available. The interactions of Cu(2+) with oligopeptides were also analysed using surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-ToF MS). The results provide an insight into the metal complex species formed, their apparent stabilities under selected conditions and the effect of the relative positions of certain amino acids within the peptide sequence. PMID- 22085538 TI - Biogenic amines in the nervous system of the cockroach, Periplaneta americana following envenomation by the jewel wasp, Ampulex compressa. AB - The emerald jewel wasp, Ampulex compressa, exploits the American cockroach, Periplaneta americana, as a host for its progeny. The wasp subdues the host by stinging directly into the brain and subesophageal ganglion, inducing long-term hypokinesia. The hypokinesic host lacks normal escape behavior and motivation to walk, making it easy for subjugation by the wasp. The mechanism underlying hypokinesia induction is not known, but depletion of monoamines induces behavior resembling venom-induced hypokinesia. To test whether amine depletion occurs in stung animals, we used high-performance liquid chromatography with electrochemical detection (HPLC-ED) to measure quantitatively amine levels in the central nervous system. Our data show clearly that levels of dopamine, serotonin, octopamine and tyramine remain unchanged in stung animals, whereas animals treated with reserpine exhibited marked depletion of all amines sampled. Furthermore, stung animals treated with reserpine show depletion of amines, demonstrating that envenomation also does not interfere with amine release. These results show that hypokinesia induced by Ampulex venom does not result from amine depletion or inability to release monoamines in the central nervous system. PMID- 22085539 TI - Determination of fatty acids in broiler breast meat by near-infrared reflectance spectroscopy. AB - The aim of this study was to develop near-infrared reflectance spectroscopy (NIRS) calibrations for determination of the fatty acids (FA) in broiler breast meat. A total of 144 breast meat samples were freeze-dried and divided into calibration set and validation set. Calibration models were developed for FA including C14:0, C16:0, C16:1n-7, C18:0, C18:1n-7, C18:1n-9, C18:2n-6, C18:3n-3, C18:3n-6, C20:0, C20:1n-9, C20:2n-6, C20:4n-6, C20:5n-3, C22:4n-6, C22:6n-3, C24:0 and C24:1n-9. Calibration models for FA groups were also developed. Calibrations based on the absolute FA content were more accurate than those based on the relative composition (%). The coefficients of determination of FA and FA groups (based on the absolute content) except C18:3n-6, C20:0, C20:2n-6 and C24:1n-9, were between 0.86 and 0.98 for calibration, and 0.83 and 0.97 for validation. The results indicate NIRS can be a feasible and rapid method for determination of FA with a mean concentration over 0.10g/kg. PMID- 22085540 TI - OmniMapFree: a unified tool to visualise and explore sequenced genomes. AB - BACKGROUND: Acquiring and exploring whole genome sequence information for a species under investigation is now a routine experimental approach. On most genome browsers, typically, only the DNA sequence, EST support, motif search results, and GO annotations are displayed. However, for many species, a growing volume of additional experimental information is available but this is rarely searchable within the landscape of the entire genome. * RESULTS: We have developed a generic software which permits users to view a single genome in entirety either within its chromosome or supercontig context within a single window. This software permits the genome to be displayed at any scales and with any features. Different data types and data sets are displayed onto the genome, which have been acquired from other types of studies including classical genetics, forward and reverse genetics, transcriptomics, proteomics and improved annotation from alternative sources. In each display, different types of information can be overlapped, then retrieved in the desired combinations and scales and used in follow up analyses. The displays generated are of publication quality. * CONCLUSIONS: OmniMapFree provides a unified, versatile and easy-to-use software tool for studying a single genome in association with all the other datasets and data types available for the organism. PMID- 22085541 TI - Heterologous production and characterisation of two distinct dihaem-containing membrane integral cytochrome b(561) enzymes from Arabidopsis thaliana in Pichia pastoris and Escherichia coli cells. AB - Cytochrome (cyt) b(561) proteins are dihaem-containing membrane proteins, belonging to the CYBASC (cytochrome-b(561)-ascorbate-reducible) family, and are proposed to be involved in ascorbate recycling and/or the facilitation of iron absorption. Here, we present the heterologous production of two cyt b(561) paralogs from Arabidopsis thaliana (Acytb(561)-A, Acytb(561)-B) in Escherichia coli and Pichia pastoris, their purification, and initial characterisation. Spectra indicated that Acytb(561)-A resembles the best characterised member of the CYBASC family, the cytochrome b(561) from adrenomedullary chromaffin vesicles, and that Acytb(561)-B is atypical compared to other CYBASC proteins. Haem oxidation-reduction midpoint potential (E(M)) values were found to be fully consistent with ascorbate oxidation activities and Fe(3+)-chelates reductase activities. The ascorbate dependent reduction and protein stability of both paralogs were found to be sensitive to alkaline pH values as reported for the cytochrome b(561) from chromaffin vesicles. For both paralogs, ascorbate dependent reduction was inhibited and the low-potential haem E(M) values were affected significantly by incubation with diethyl pyrocarbonate (DEPC) in the absence of ascorbate. Modification with DEPC in the presence of ascorbate left the haem E(M) values unaltered compared to the unmodified proteins. However, ascorbate reduction was inhibited. We concluded that the ascorbate-binding site is located near the low-potential haem with the Fe(3+)-chelates reduction-site close to the high-potential haem. Furthermore, inhibition of ascorbate oxidation by DEPC treatment occurs not only by lowering the haem E(M) values but also by an additional modification affecting ascorbate binding and/or electron transfer. Analytical gel filtration experiments suggest that both cyt b(561) paralogs exist as homodimers. PMID- 22085542 TI - CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration. AB - Epithelial cells are largely immotile under normal circumstances, but become motile during development, repair of tissue damage and during cancer metastasis. Numerous growth factors act to initiate epithelial cell movements. Hepatocyte growth factor (HGF) induces many epithelial cell lines to begin crawling. A number of small GTPases act downstream of HGF to alter cell shape and promote movement. Arf6 is one of these GTPases that can alter the cortical actin cytoskeleton and promote epithelial movement. Activation of Arf6 in MDCK cells by its guanine nucleotide exchange factor cytohesin 2/ARNO produces a scattering response strikingly reminiscent of the action of HGF. We have previously shown that IPCEF1, a scaffold that binds to cytohesin 2, is required for cytohesin induced scattering. We report here that IPCEF1 is actually the C-terminal half of CNK3. CNKs are scaffolds involved in signal transduction downstream of Ras. We have found that both MDCK and CaCo-2 cells express a fused CNK3/IPCEF1 protein. Knockdown of this protein impairs HGF-induced Arf6 activation and migration in response to HGF treatment. PMID- 22085544 TI - Optical properties of exfoliated MoS2 coaxial nanotubes - analogues of graphene. AB - We report on the first exfoliation of MoS2 coaxial nanotubes. The single-layer flakes, as the result of exfoliation, represent the transition metal dichalcogenides' analogue of graphene. They show a very low degree of restacking in comparison with exfoliation of MoS2 plate-like crystals. MoS2 monolayers were investigated by means of electron and atomic force microscopies, showing their structure, and ultraviolet-visible spectrometry, revealing quantum confinement as the consequence of the nanoscale size in the z-direction. PMID- 22085543 TI - Long-term perturbation of muscle iron homeostasis following hindlimb suspension in old rats is associated with high levels of oxidative stress and impaired recovery from atrophy. AB - In the present study, we investigated the effects of 7 and 14 days of re-loading following 14-day muscle unweighting (hindlimb suspension, HS) on iron transport, non-heme iron levels and oxidative damage in the gastrocnemius muscle of young (6 months) and old (32 months) male Fischer 344*Brown Norway rats. Our results demonstrated that old rats had lower muscle mass, higher levels of total non-heme iron and oxidative damage in skeletal muscle in comparison with young rats. Non heme iron concentrations and total non-heme iron amounts were 3.4- and 2.3-fold higher in aged rats as compared with their young counterparts, respectively. Seven and 14 days of re-loading was associated with higher muscle weights in young animals as compared with age-matched HS rats, but there was no difference in muscle weights among aged HS, 7 and 14 days of re-loading rats, indicating that aged rats may have a lower adaptability to muscle disuse and a lower capacity to recover from muscle atrophy. Protein levels of cellular iron transporters, such as divalent metal transport-1 (DMT1), transferrin receptor-1 (TfR1), Zip14, and ferroportin (FPN), and their mRNA abundance were determined. TfR1 protein and mRNA levels were significantly lower in aged muscle. Seven and 14 days of re-loading were associated with higher TfR1 mRNA and protein levels in young animals in comparison with their age-matched HS counterparts, but there was no difference between cohorts in aged animals, suggesting adaptive responses in the old to cope with iron deregulation. The extremely low expression of FPN in skeletal muscle might lead to inefficient iron export in the presence of iron overload and play a critical role in age-related iron accumulation in skeletal muscle. Moreover, oxidative stress was much greater in the muscles of the older animals measured as 4-hydroxy-2-nonhenal (HNE)-modified proteins and 8-oxo-7,8 dihydroguanosine levels. These markers remained fairly constant with either HS or re-loading in young rats. In old rats, HNE-modified proteins and 8-oxo-7,8 dihydroguanosine levels were markedly higher in HS and were lower after 7 days of recovery. However, no difference was observed following 14 days of recovery between control and re-loading animals. In conclusion, advanced age is associated with disruption of muscle iron metabolism which is further perturbed by disuse and persists over a longer time period. PMID- 22085545 TI - Cationic liposome-DNA complexes (CLDC) adjuvant enhances the immunogenicity and cross-protective efficacy of a pre-pandemic influenza A H5N1 vaccine in mice. AB - The development of pre-pandemic influenza A H5N1 vaccines that confer both antigen-sparing and cross-clade protection are a high priority given the limited worldwide capacity for influenza vaccine production, and the antigenic and genetic heterogeneity of circulating H5N1 viruses. The inclusion of potent adjuvants in vaccine formulations may achieve both of these aims. Here we show that the addition of JVRS-100, an adjuvant consisting of cationic liposome-DNA complexes (CLDC) to a clade 1-derived H5N1 split vaccine induced significantly higher virus-specific antibody than unadjuvanted formulations, with a >30-fold dose-sparing effect and induction of increased antigen-specific CD4(+) T-cell responses in mice. All mice that received one dose of adjuvanted vaccine and subsequent H5N1 viral challenges exhibited mild illness, lower lung viral titers, undetectable spleen and brain viral titers, and 100% survival after either homologous clade 1 or heterologous clade 2 H5N1 viral challenges, whereas unadjuvanted vaccine recipients showed significantly increased weight loss, viral titers, and mortality. The protective immunity induced by JVRS-100 adjuvanted H5N1 vaccine was shown to last for over one year without significant waning. Thus, JVRS-100 adjuvanted H5N1 vaccine elicited enhanced humoral and T-cell responses, dose-sparing, and cross-clade protection in mice. CLDC holds promise as an adjuvant for human pre-pandemic inactivated H5N1 vaccines. PMID- 22085546 TI - Differential effects of monophosphoryl lipid A and cytokine cocktail as maturation stimuli of immunogenic and tolerogenic dendritic cells for immunotherapy. AB - Immunotherapy using monocyte-derived dendritic cells (MDDC) is increasingly being considered as alternative therapeutic approach in cancer, infectious diseases and also in autoimmunity when patients are not responsive to conventional treatments. In general, generation of MDDC from monocytes is induced in the presence of GM CSF and IL-4, and a maturation stimulus is added to the culture to obtain mature DCs suitable for therapy. For DC maturation, different combinations of pro inflammatory mediators and Toll-like receptor ligands have been tested, obtaining DCs that differ in their properties and the type of immune response they promote. Therefore, it is necessary to find an optimal cytokine environment for DC maturation to obtain a cellular product suitable for DC-based immunotherapeutic protocols. In this study, we have evaluated in vitro the effects of different maturation stimuli on the viability, phenotype, cytokine profile, stability and functionality of immunogenic and tolerogenic (1alpha,25-dihydroxyvitamin D(3) treated) MDDC. Maturation was induced using the clinical grade TLR4-agonist: monophosphoryl lipid A (LA), compared to the traditional cytokine cocktail (CC; clinical grade TNF-alpha, IL-1beta, PGE2) and a combination of both. Our results showed the combination of CC+LA rendered a potent immunogenic DC population that induced the production of IFN-gamma and IL-17 in allogeneic co-cultures, suggesting a Th17 polarization. Moreover, these immunogenic DCs showed a high surface expression of CD83, CD86, HLA-DR and secretion of IL-12p70. When aiming to induce tolerance, using LA to generate mature TolDC did not represent a clear advantage, and the stability and the suppressive capability exhibited by CC matured TolDC may represent the best option. Altogether, these findings demonstrate the relevance of an appropriate maturation stimulus to rationally modulate the therapeutic potential of DCs in immunotherapy. PMID- 22085547 TI - Direct and indirect impact of influenza vaccination of young children on school absenteeism. AB - Special mass influenza vaccination programs of elementary school-aged children (ESAC) in some or all Maryland Counties were conducted during the falls of 2005 2007. From 3% to 46% of ESAC received live attenuated influenza vaccine during these county programs, which were in addition to routine influenza vaccination efforts conducted in county medical offices. Anonymous, all cause public school absentee data for all grades was available from 11 of Maryland's 24 counties. Binomial regression was used to estimate associations between the percentage of children vaccinated in each county and the degree of increase in absenteeism rates during influenza outbreaks. We estimated that, for every 20% increase in vaccination rates for ESAC during these special programs, a 4% decrease in the rise in absentee rates occurred during influenza outbreak periods in both elementary and upper schools (P<0.05). These results suggest both direct and indirect benefits of influenza vaccination of young children. PMID- 22085548 TI - Immunogenicity and protective efficacy of a vaxfectin-adjuvanted tetravalent dengue DNA vaccine. AB - A prototype dengue-1 DNA vaccine was shown to be safe and immunogenic in a previous Phase 1 clinical trial. Anti-dengue-1 neutralizing antibody responses were detectable only in the group of volunteers receiving the high dose of nonadjuvanted vaccine and the antibody titers were low. Vaxfectin((r)), a lipid based adjuvant, enhances the immunogenicity of DNA vaccines. We conducted a nonhuman primate study to evaluate the effect of Vaxfectin((r)) on the immunogenicity of a tetravalent dengue DNA vaccine. Animals were immunized on days 0, 28 and 84, with each immunization consisting of 3mg of Vaxfectin((r)) adjuvanted tetravalent dengue DNA vaccine. The use of Vaxfectin((r)) resulted in a significant increase in anti-dengue neutralizing antibody responses against dengue-1, -3 and -4. There was little to no effect on T cell responses as measured by interferon gamma ELISPOT assay. Animals immunized with the Vaxfectin((r))-formulated tetravalent DNA vaccine showed significant protection against live dengue-2 virus challenge compared to control animals (0.75 mean days of viremia vs 3.3 days). Animals vaccinated with nonadjuvanted DNA had a mean 2.0 days of viremia. These results support further evaluation of the Vaxfectin((r)) adjuvanted tetravalent dengue DNA vaccine in a Phase 1 clinical trial. PMID- 22085549 TI - Control of tick infestations in cattle vaccinated with bacterial membranes containing surface-exposed tick protective antigens. AB - Vaccines containing the Rhipicephalus (Boophilus) microplus BM86 and BM95 antigens protect cattle against tick infestations. Tick subolesin (SUB), elongation factor 1a (EF1a) and ubiquitin (UBQ) are new candidate protective antigens for the control of cattle tick infestations. Previous studies showed that R. microplus BM95 immunogenic peptides fused to the Anaplasma marginale major surface protein (MSP) 1a N-terminal region (BM95-MSP1a) for presentation on the Escherichia coli membrane were protective against R. microplus infestations in rabbits. In this study, we extended these results by expressing SUB-MSP1a, EF1a-MSP1a and UBQ-MSP1a fusion proteins on the E. coli membrane using this system and demonstrating that bacterial membranes containing the chimeric proteins BM95-MSP1a and SUB-MSP1a were protective (>60% vaccine efficacy) against experimental R. microplus and Rhipicephalus annulatus infestations in cattle. This system provides a novel, simple and cost-effective approach for the production of tick protective antigens by surface display of antigenic protein chimera on the E. coli membrane and demonstrates the possibility of using recombinant bacterial membrane fractions in vaccine preparations to protect cattle against tick infestations. PMID- 22085550 TI - Impact of vaccination against Haemophilus influenzae type b with and without a booster dose on meningitis in four South American countries. AB - To inform World Health Organization recommendations regarding use of Haemophilus influenzae type b (Hib) vaccines in national immunization programs, a multi country evaluation of trends in Hib meningitis incidence and prevalence of nasopharyngeal Hib carriage was conducted in four South American countries using either a primary, three-dose immunization schedule without a booster dose or with a booster dose in the second year of life. Surveillance data suggest that high coverage of Hib conjugate vaccine sustained low incidence of Hib meningitis and low prevalence of Hib carriage whether or not a booster dose was used. PMID- 22085551 TI - Development of orf virus as a bifunctional recombinant vaccine: surface display of Echinococcus granulosus antigen EG95 by fusion to membrane structural proteins. AB - The parapoxvirus, orf virus (ORFV) causes superficial skin lesions in infected sheep. Unattenuated ORFV is used globally to vaccinate against orf. Recombinant poxviruses are proven delivery systems and we investigated strategies to express the immunogenic Echinococcus granulosus peptide EG95 from ORFV with the aim of developing a recombinant bivalent vaccine. EG95 is an oncosphere protein of the cestode E. granulosus, a parasite responsible for causing cystic hydatid disease in a wide range of hosts including humans and grazing animals such as sheep. Recombinant viruses were produced in which EG95 was expressed by itself or fused to ORFV envelope-associated structural proteins 10 kDa and F1L. Infection studies in sheep showed that specific antibodies were produced against ORFV and EG95 and that the antibody levels against EG95 were comparable to that of animals immunized with purified EG95 in Quil A adjuvant, an immunization regime that is known to afford protection. A single exposure to the dual vaccine has potential for protecting lambs against orf and for priming against EG95 so as to respond strongly to a later injection of EG95 protein. PMID- 22085552 TI - Replication and pathogenicity of attenuated human metapneumovirus F mutants in severe combined immunodeficiency mice. AB - This study was to evaluate the replication and pathogenicity of attenuated human metapneumovirus (HMPV) mutants in severe combined immunodeficiency (SCID) mice. SCID mice were intranasally infected with either wild type GFP-rHMPV (WT), or mutant viruses (M1, M2 and M4) with the N-linked glycosylation(s) of the F protein removed. The organs were collected for viral isolation, titration, pulmonary histopathology and mRNA detection by PCR at different time points. WT or mutant viruses were successfully isolated from the lungs of infected mice after inoculation. The titers of WT and M1 peaked on 5th day and remained detectable until 14th day post-inoculation. M2 reached approximately 4 logs lower titer on 5th and 9th day post-inoculation as compared to WT and M1. M4 showed similar growth kinetics to M2. Viral signal was never detected from the heart, liver, spleen, kidney and brain on 5th day post-inoculation. The pulmonary pathology score in the M1 infected mice was similar to WT infected mice but higher than in M2 or M4 infected mice. WT and HMPV mutants can thus only replicate in the lungs of SCID mice. Attenuated M2 and M4 may be considered as candidates for the preparation of vaccine against HMPV. PMID- 22085554 TI - HLA class II restriction of HIV-1 clade-specific neutralizing antibody responses in ethnic Thai recipients of the RV144 prime-boost vaccine combination of ALVAC HIV and AIDSVAX((r)) B/E. AB - Immune responses to vaccines may be influenced or associated with allelic variants of host genes such as those encoding human leucocyte antigens (HLA). We have molecularly determined the HLA class II DR and DQ gene, allele and haploype profiles in HIV-1 negative ethnic Thai recipients of an HIV-1 prime boost vaccine regimen, designed to induce neutralizing antibody (NAb) responses to HIV-1 CRF01_AE. Non-response to vaccine associated with DRB1*11 (3/32 responders vs. 7/13 non-responders, p(c)=0.027) and DRB1*16:02 (0/32 responders vs. 4/13 non responders, p(c)=0.078) alleles. Furthermore, vaccine recipients with HLA-DQ heterodimers encoded by DQA1*05:01 and DQB1*03:01 alleles, were much less likely to produce NAb (p=0.009). These data suggest that the lack of response to a vaccine designed to induce clade-specific NAb to HIV-1 is associated with the presence of certain HLA class II alleles and heterodimers in some Southeast Asians. PMID- 22085553 TI - The development and clinical evaluation of second-generation leishmaniasis vaccines. AB - Infection with Leishmania parasites results in a range of clinical manifestations and outcomes. Control of Leishmania parasite transmission is extremely difficult due to the large number of vectors and potential reservoirs, and none of the current treatments are ideal. Vaccination could be an effective strategy to provide sustained control. In this review, the current global situation with regard to leishmaniasis, the immunology of Leishmania infection and various efforts to identify second generation vaccine candidates are briefly discussed. The variety of clinical trials conducted using the only current second generation vaccine approved for clinical use, LEISH-F1+MPL-SE, are described. Given that epidemiological evidence suggests that reducing the canine reservoir also positively impacts human incidence, efforts at providing a vaccine for leishmaniasis in dogs are highlighted. Finally, potential refinements and surrogate markers that could expedite the introduction of a vaccine that can limit the severity and incidence of leishmaniasis are discussed. PMID- 22085555 TI - Direct costs of a single case of refugee-imported measles in Kentucky. AB - BACKGROUND: Refugees are highly vulnerable populations with limited access to health care services. The United States accepts 50,000-75,000 refugees for resettlement annually. Despite residing in camps and other locations where vaccine-preventable disease outbreaks, such as measles, occur frequently, refugees are not required to have any vaccinations before they arrive in the United States. PURPOSE: We estimated the medical and public-health response costs of a case of measles imported into Kentucky by a refugee. METHODS: The Kentucky Refugee Health Coordinator recorded the time and labor of local, state, and some federal personnel involved in caring for the refugee and implementing the public health response activities. Secondary sources were used to estimate the labor and medical care costs of the event. RESULTS: The total costs to conduct the response to the disease event were approximately $25,000. All costs were incurred by government, either public health department or federal, because refugee health costs are paid by the federal government and the event response costs are covered by the public health department. CONCLUSION: A potentially preventable case of measles that was imported into the United States cost approximately $25,000 for the public health response. RECOMMENDATION: To maintain the elimination of measles transmission in the United States, U.S.-bound refugees should be vaccinated overseas. A refugee vaccination program administered during the overseas health assessment has the potential to reduce the risk of importation of measles and other vaccine-preventable disease and would eliminate costs associated with public health response to imported cases and outbreaks. PMID- 22085556 TI - New insights in mucosal vaccine development. AB - Mucosal surfaces are the major entrance for infectious pathogens and therefore mucosal immune responses serve as a first line of defence. Most current immunization procedures are obtained by parenteral injection and only few vaccines are administered by mucosal route, because of its low efficiency. However, targeting of mucosal compartments to induce protective immunity at both mucosal sites and systemic level represents a great challenge. Major efforts are made to develop new mucosal candidate vaccines by selecting appropriate antigens with high immunogenicity, designing new mucosal routes of administration and selecting immune-stimulatory adjuvant molecules. The aim of mucosal vaccines is to induce broad potent protective immunity by specific neutralizing antibodies at mucosal surfaces and by induction of cellular immunity. Moreover, an efficient mucosal vaccine would make immunization procedures easier and be better suited for mass administration. This review focuses on contemporary developments of mucosal vaccination approaches using different routes of administration. PMID- 22085557 TI - Rabies vaccination for international travelers. AB - Rabies prevention in travelers is a controversial issue. According to experts, the decision to vaccinate results from an individual risk assessment based on the duration of stay, the likelihood of engagement in at-risk activities, the age of the traveler, the rabies endemicity and access to appropriate medical care in the country of destination. However, no detailed information is available regarding the last two determinants in many regions. Twenty-two cases of rabies were reported in tourists, expatriates and migrant travelers over the last decade, including three cases following short-term travel of no more than two weeks. Studies on rabies post-exposure prophylaxis (PEP) in travelers show that overall, 0.4% (range 0.01-2.3%) of travelers have experienced an at-risk bite per month of stay in a rabies-endemic country, while 31% of expatriates and 12% of tourists were vaccinated against rabies before traveling. The main reason cited by travelers for not being vaccinated is the cost of the vaccine. The majority of patients who sustained a high risk injury was not vaccinated against rabies before traveling and were not properly treated abroad. From available studies, the following risk factors for injuries sustained from potentially rabid animals may be identified: traveling to South-East Asia, India or North Africa, young age, and traveling for tourism. The duration of travel does not appear to be a risk factor. It should be noted that "at-risk activities" have not been addressed in these studies. Detailed rabies distribution maps and information on the availability of rabies biologics are urgently needed in order to identify those travelers who need pre-travel vaccination. Meanwhile, cost-minimization of rabies pre-exposure vaccination may be achieved in several ways, notably by using the intra-dermal method of vaccination. PMID- 22085558 TI - Mechanisms of endometrial progesterone resistance. AB - Throughout the reproductive years, the rise and fall in ovarian hormones elicit in the endometrium waves of cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown and regeneration. The activated progesterone receptor, a member of the superfamily of ligand-dependent transcription factors, is the master regulator of this intense tissue remodelling process in the uterus. Its activity is tightly regulated by interaction with cell specific transcription factors and coregulators as well as by specific posttranslational modifications that respond dynamically to a variety of environmental and inflammatory signals. Endometriosis, a chronic inflammatory disorder, disrupts coordinated progesterone responses throughout the reproductive tract, including in the endometrium. This phenomenon is increasingly referred to as 'progesterone resistance'. Emerging evidence suggests that progesterone resistance in endometriosis is not just a consequence of perturbed progesterone signal transduction caused by chronic inflammation but associated with epigenetic chromatin changes that determine the intrinsic responsiveness of endometrial cells to differentiation cues. PMID- 22085559 TI - New paradigms in cAMP signalling. AB - Signalling through adenosine 3'5' monophosphate (cAMP) is known to be important in virtually every cell. The mapping of the human genome over the past two decades has revealed an unexpected complexity of cAMP signalling, which is shared from insects to mammals. A more recent technical advance is the ability to monitor intracellular cAMP levels at subcellular spatial resolution within the time-domains of fast biochemical reactions. Thus, new light has been shed on old paradigms, some of which turn out to be multiple new ones. The novel aspects of cAMP signalling are highlighted here: (1) agonist induced plasticity - showing how the repertory of cAMP signalling genes supports homeostatic adaptation; (2) sustained cAMP signalling after endocytosis; (3) pre-assembled receptor-Gs adenylyl cyclase complexes. Finally, a hypothetical model of propagating neuronal cAMP signals travelling form dendrites to the cell body is presented. PMID- 22085560 TI - 4-Hydroxynonenal differentially regulates adiponectin gene expression and secretion via activating PPARgamma and accelerating ubiquitin-proteasome degradation. AB - Although well-established, the underlying mechanisms involved in obesity-related plasma adiponectin decline remain elusive. Oxidative stress is associated with obesity and insulin resistance and considered to contribute to the progression toward obesity-related metabolic disorders. In this study, we investigated the effects of 4-hydroxynonenal (4-HNE), the most abundant lipid peroxidation end product, on adiponectin production and its potential implication in obesity related adiponectin decrease. Long-term high-fat diet feeding led to obesity in mouse, accompanied by decreased plasma adiponectin and increased adipose tissue 4 HNE content. Exposure of adipocytes to exogenous 4-HNE resulted in decreased adiponectin secretion in a dose-dependent manner, which was consistent with significantly decreased intracellular adiponectin protein abundance. In contrast, adiponectin gene expression was significantly elevated by 4-HNE treatment, which was concomitant with increased peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene expression and transactivity. The effect was abolished by T0070907, a PPAR-gamma antagonist, suggesting that PPAR-gamma activation plays a critical role in this process. To gain insight into mechanisms involved in adiponectin protein decrease, we examined the effects of 4-HNE on adiponectin protein degradation. Cycloheximide (CHX)-chase assay revealed that 4-HNE exposure accelerated adiponectin protein degradation, which was prevented by MG132, a potent proteasome inhibitor. Immunoprecipitation assay showed that 4-HNE exposure increased ubiquitinated adiponectin protein levels. These data altogether indicated that 4-HNE enhanced adiponectin protein degradation via ubiquitin proteasome system. Finally, we demonstrated that supplementation of HF diet with betaine, an antioxidant and methyl donor, alleviated high-fat-induced adipose tissue 4-HNE increase and attenuated plasma adiponectin decline. Taken together, our findings suggest that the lipid peroxidation product 4-HNE can differentially regulates adiponectin gene expression and protein abundance and may play a mechanistic role in obesity-related plasma adiponectin decline. PMID- 22085562 TI - [A woman with 'year rings' on her nails]. AB - A 50-year-old woman developed Mees' lines on her nails after chemotherapy for infiltrating lobulair carcinoma of the breast. PMID- 22085561 TI - Characterization of highly efficient heavy-ion mutagenesis in Arabidopsis thaliana. AB - BACKGROUND: Heavy-ion mutagenesis is recognised as a powerful technology to generate new mutants, especially in higher plants. Heavy-ion beams show high linear energy transfer (LET) and thus more effectively induce DNA double-strand breaks than other mutagenic techniques. Previously, we determined the most effective heavy-ion LET (LETmax: 30.0 keV MUm(-1)) for Arabidopsis mutagenesis by analysing the effect of LET on mutation induction. However, the molecular structure of mutated DNA induced by heavy ions with LETmax remains unclear. Knowledge of the structure of mutated DNA will contribute to the effective exploitation of heavy-ion beam mutagenesis. RESULTS: Dry Arabidopsis thaliana seeds were irradiated with carbon (C) ions with LETmax at a dose of 400 Gy and with LET of 22.5 keV MUm(-1) at doses of 250 Gy or 450 Gy. The effects on mutation frequency and alteration of DNA structure were compared. To characterise the structure of mutated DNA, we screened the well-characterised mutants elongated hypocotyls (hy) and glabrous (gl) and identified mutated DNA among the resulting mutants by high-resolution melting curve, PCR and sequencing analyses. The mutation frequency induced by C ions with LETmax was two-fold higher than that with 22.5 keV MUm(-1) and similar to the mutation frequency previously induced by ethyl methane sulfonate. We identified the structure of 22 mutated DNAs. Over 80% of the mutations caused by C ions with both LETs were base substitutions or deletions/insertions of less than 100 bp. The other mutations involved large rearrangements. CONCLUSIONS: The C ions with LETmax showed high mutation efficiency and predominantly induced base substitutions or small deletions/insertions, most of which were null mutations. These small alterations can be determined by single-nucleotide polymorphism (SNP) detection systems. Therefore, C ions with LETmax might be useful as a highly efficient reverse genetic system in conjunction with SNP detection systems, and will be beneficial for forward genetics and plant breeding. PMID- 22085564 TI - [Measuring quality of life in every oncological patient]. AB - There are indications that in cancer patients quality of life is a better predictor of survival than clinical measures such as tumour response and stage of disease. In addition, health care professionals' expectations about the effect of a particular treatment on quality of life often do not correspond with the experience of the patient. These are all reasons for every oncological patient to complete a short questionnaire on quality of life. Using this questionnaire can improve communication between care provider and patient, and also give the care provider insight into the problems that are important to the patient at that time. This insight could subsequently lead to counseling tailored to the patient, and, if necessary, modification of treatment or referral for supportive care. A second aim is to link information on quality of life to clinical pathways and treatment guidelines. PMID- 22085565 TI - [Scalp cooling for chemotherapy-induced alopecia]. AB - Alopecia is a very common side effect of cytostatic therapy and is considered one of the most emotionally distressing effects. To prevent alopecia scalp cooling is currently used in some indications in medical oncology in 59 hospitals in the Netherlands. The success of scalp cooling depends on various factors such as type of chemotherapy, dose, infusion time, number of treatment cycles and combinations of drugs. In general, scalp cooling is well tolerated. The reported side-effects are headache, coldness, dizziness and sometimes claustrophobia. An increase in the risk of scalp metastases has not been demonstrated. Proceeding from the South Netherlands Comprehensive Cancer Centre a national working group is put together in order to draw up a national guideline for chemotherapy-induced alopecia. PMID- 22085566 TI - [Issues around diffuse glioma]. AB - Progress in treating diffuse gliomas remains limited and is principally concerned with the confirmation that cystostatics as nitrosureum derivatives and temozolomide play a role in the treatment of these tumours. At molecular level, diffuse gliomas are a heterogeneous group of tumours. This seems to be an important explanation of why so far no important breakthrough in the treatment of these tumours has been achieved. It is thought that abnormal activation of various molecular signal systems working in parallel in the tumour cell are an important cause of the absence of efficacy of the targeted agents; the inhibition of only one target appears inadequate. PMID- 22085567 TI - [Centralising cancer treatment: a good idea]. AB - The complexity of diagnosis and treatment for common cancers is rapidly increasing due to multimodality treatment options, advanced imaging, molecular pathology and 'personalized medicine'. To achieve the best chances for cure, treatment centres need to invest in highly trained personnel, including all the necessary diagnostic and therapeutic subspecialists, and in high-tech facilities. In the Netherlands, many patients receive care in community hospitals that lack key members of a treatment team (e.g. the radiotherapist). Such teams may depend on weekly or biweekly cancer conferences with external experts to arrive at patient-management decisions. It is recommended that such hospitals either upgrade their teams and facilities or refer their patients to a hospital that has an established cancer centre. PMID- 22085568 TI - [Issues around melanoma]. AB - Over the past 30 years little progress has been made in the treatment of patients with a metastatic melanoma. Recently there have been two new developments. One of these is ipilimumab, a monoclonal antibody that blocks the function of the protein cytotoxic T lymphocyte-associated antigen 4 (CTLA4) which inhibits activated T lymphocytes. This gives the immune system a chance to build up an immune response to the melanoma. The other development is vemurafenib, a small molecule that inhibits a mutated protein (BRAF) that occurs in many melanomas. The BRAF mutation leads to uninhibited proliferation. PMID- 22085569 TI - [Centralising cancer treatment: there are better ways]. AB - The Netherlands is strongly leaning towards treating cancer patients at a limited number of hospitals. This approach has been poorly investigated and there is little evidence that the quality of care and the outcome of treatment in the Dutch system are related to the size of the institute. Oncological care is getting more and more complicated and requires a certain scale, but the formation of networks offers more possibilities than centralisation. Technical developments may offer alternatives to centralisation. In addition, care given closer to home to an increasingly older patient population is very valuable. Comorbidity is another reason to provide care at a general hospital in close cooperation with general practitioners. Strong ties with a university clinic is an important requirement for such a network to work well. PMID- 22085570 TI - [Moritz Kaposi and his sarcoma]. AB - Nowadays, Kaposi sarcoma is a multidisciplinary condition, not only observed by dermatologists. Since the HIV epidemic in the 80s and 90s of the last century, more insight into the aetiology of Kaposi sarcoma has been acquired. However, this sarcoma had already been described in 1872 by a Hungarian dermatologist named Moritz Kaposi (1832-1902). Kaposi described the entity as 'idiopathic multiple pigmented sarcoma of the skin'. This entity was an extraordinary diagnosis at that time, mostly observed in Jewish or Mediterranean men. In 1912, 10 years after the death of Moritz Kaposi, the entity name was changed to Kaposi sarcoma. PMID- 22085571 TI - [Adjuvant cancer treatment: what benefit does the patient consider worthwhile?]. AB - Adjuvant treatments can be added to primary curative cancer treatments to increase the probability of survival. However, these treatments have side effects. Research into what additional probability of survival cancer patients require from an adjuvant treatment before they consider it worthwhile, has been carried out in hypothetical situations. The published literature on this subject shows that the additional benefit which patients expect is small. Yet, variation in patient preferences within studies is large. Preferences regarding additional benefit are not consistently associated with patient socio-demographic or disease characteristics. It is very likely that new patients who face the choice of adjuvant treatment will greatly differ from each other in the benefit that they require from it. In order to give individualized recommendations, specialists need to ask the patient which benefits and disadvantages he or she considers to be important. PMID- 22085572 TI - [A spontaneously resolving T-cell lymphoma]. AB - BACKGROUND: Primary cutaneous CD30+ anaplastic large-cell lymphoma is a rare form of non-Hodgkin's lymphoma, which is restricted to the skin. CASE DESCRIPTION: A 50-year-old man presented with an asymptomatic tumorous area in the groin that had appeared within the previous week, and a longer history of a transient red, flaking area in the popliteal space. Histopathological findings were consistent with CD30+ anaplastic large-cell lymphoma. Staging demonstrated no extracutanous spread. The skin lesions disappeared without treatment within 3 months. CONCLUSION: Primary cutaneous CD30+ anaplastic large-cell lymphoma is a rare condition. It has a histopathological picture of a diffuse proliferation of large atypical anaplastic cells, suggesting an unfavourable disease course. However, this condition is characterised by a indolent course and favourable prognosis since spontaneous complete regression can occur. PMID- 22085573 TI - [Responsible cancer screening]. AB - In the Netherlands, national screening programs for breast and cervical cancer are operating, whilst that for colorectal cancer is in preparation. In the meantime, experimental studies have been conducted into the effectiveness of prostate and lung cancer screening. Death from these five types of cancer is reduced by these screening investigations. However, these screening programmes also have disadvantages, such as unnecessary referral for definitive diagnosis in the hospital. The average hospital would receive on a yearly basis via screening 156 referrals of women with breast cancer, 79 for cervical cancer and nearly 1100 persons for colorectal cancer. n average general practice encounters annually 3 positive screening results for breast cancer, almost 1 referral for cervical carcinoma or an early stage thereof, and every two years a patient with CIN III. For colorectal cancer around 22 referrals can be expected yearly, of which 8 will have adenoma or cancer. PMID- 22085574 TI - [A man with blisters on hand and feet]. AB - A 41-year-old man with metastases of a gastrointestinal stroma tumour was treated with an angiogenesis inhibitor. He presented with a distinct painful erythematous hyperkeratotic bullous hand-foot skin reaction. This was thought to be caused by the oral angiogenesis inhibitor and resolved after discontinuation of the therapy. This is a known adverse effect of angiogenesis inhibitors and is dose dependent. PMID- 22085575 TI - [New 'targeted therapy' for lung cancer]. AB - Patients with non-small cell lung cancer with specific mutations for which so called 'targeted therapy' is available are likely to have a favourable tumour response. The first patient, a man aged 64 with an activating epidermal growth factor receptor (EGFR) mutation, had a longstanding tumour response on erlotinib, an EGFR tyrosine kinase inhibitor (TKI). After 16 months on treatment, there was still no progression of the disease. The next patient, a woman aged 78, also responded favourably to erlotinib After 2.5 years she discontinued the medication and the disease recurred. Remission was induced again with the use of erlotinib, but the recovery was of short duration and she died a few months later. A third patient, a 66-year-old man, developed resistance to erlotinib due to a T790M mutation in the EGFR protein. He responded well to a combination of the irreversible EGFR-TKI afatinib and the antibody to EGFR, cetuximab. The final patient, a 47-year-old woman, had an EML4-ALK translocation and responded remarkably well to an ALK inhibitor, crozotinib. Mutation analysis should be carried out in all patients with metastatic adenocarcinoma or large cell lung cancer, specifically for genes for which a targeted therapy is already available. PMID- 22085576 TI - [Targeted therapy: the benefit of new oncological tests]. AB - An increasing number of targeted drug treatments are becoming available for many types of cancer. There is a great need for adequate biomarkers that can predict the effect of targeted therapy in individual cancer patients, in order to determine the correct oncological treatment per patient. This way, non-effective treatments can be spared, side-effects avoided, and costs reduced. Oestrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2) are examples of standardized tests for breast cancer that have been validated in randomised studies. Data from randomised studies is also expected for gene expression profiles that correlate with tumour growth. Quantifying the predictive value of tests for anticipated treatment effects is costly and time-consuming. Given the increasing availability of targeted agents and diagnostic and prognostic techniques, alternative clinical study designs that can lead to quicker and more efficient verification are being sought in many different domains. PMID- 22085577 TI - [Issues around testicular carcinoma]. AB - Testicular carcinoma is a rare tumour but the most frequently occurring form of cancer in men aged 18-35 years. In metastatic disease, following orchidectomy three or four courses of combination chemotherapy with cisplatin are given. With a general chance of cure of 80-90%, testicular cancer is still regarded as a model for a form of cancer that is curable. Due to this favourable prognosis--and to its rising incidence--the group of people who survive testicular cancer is growing and more attention is being paid to the risk of adverse consequences of treatment: secondary tumours and cardiovascular morbidity. Shared care follow-up for testicular cancer survivors with participation of both primary and secondary care is currently developed. PMID- 22085578 TI - [A woman with palmar and plantar hyperpigmentation]. AB - A 60-year-old Ghanese woman was treated with radiotherapy and capecitabine for metastatic breast cancer. 6 weeks after starting capecitabine she developed palmar and plantar hyperpigmentation, which preceded symptoms of hand-foot syndrome, a known adverse effect of capecitabine. After a dose reduction, the hand-foot syndrome diminished but the hyperpigmentation remained. 8 months later the patient was well and stable. PMID- 22085579 TI - [Follow-up in oncology: focused on the patient and the disease]. AB - Follow-up in oncology primarily encompasses medical technical examinations of patients following treatment for cancer. The term "aftercare" more accurately represents which approach should be taken after completion of cancer treatment: not only medical technical care, but fulfilment of care needs that result from the disease and its treatment. For each patient an individual aftercare plan should be put in place, which fulfils the 3 goals of aftercare: psycho-social and medical care, early diagnosis of recurrent disease or new primary disease activity if such early diagnosis bears clinical relevance, and medical audit. Involving patients in this decision-making process is generally limited in daily practice. The way in which the individual patient's aftercare is carried out, is still a scientific challenge. It is clear, however, that nothing about this is "standard". PMID- 22085580 TI - ['Clinical auditing', a novel tool for quality assessment in surgical oncology]. AB - OBJECTIVE: To determine whether systematic audit and feedback of information about the process and outcomes improve the quality of surgical care. DESIGN: Systematic literature review. METHOD: Embase, PubMed, and Web of Science databases were searched for publications on 'quality assessment' and 'surgery'. The references of the publications found were examined as well. Publications were included in the review if the effect of auditing on the quality of surgical care had been investigated. RESULTS: In the databases 2415 publications were found. After selection, 28 publications describing the effect of auditing, whether or not combined with a quality improvement project, on guideline adherence or indications of outcomes of care were included. In 21 studies, a statistically significant positive effect of auditing was reported. In 5 studies a positive effect was found, but this was either not significant or statistical significance was not determined. In 2 studies no effect was observed. 5 studies compared the combination of auditing with a quality improvement project with auditing alone; 4 of these reported an additional effect of the quality improvement project. CONCLUSION: Audit and feedback of quality information seem to have a positive effect on the quality of surgical care. The use of quality information from audits for the purpose of a quality improvement project can enhance the positive effect of the audit. PMID- 22085581 TI - [Aftercare in oncology--greater role for the general practitioner]. AB - Patients who undergo curative treatment for cancer continue to be medically monitored for a number of years. Scheduled aftercare, mainly aimed at early detection of locoregional cancer recurrences, distant metastases and secondary primary tumours, takes place chiefly in the second line, but is expected to shift to the first line. Figures from the Nijmegen Continuous Morbidity Registration show that an average (Dutch) general practitioner, caring for about 2500 patients, has in his practice 90 patients who have or have had cancer. This number will increase due to the increasing prevalence of cancer. In addition, extra consultations for each cancer patient will increase the demand for GP care. PMID- 22085582 TI - [Images of cancer: metaphors in the literature]. AB - Metaphors of cancer were once rejected by Susan Sontag, because their existence slandered the patient. There are a number of very common metaphors about cancer and the question raised is as to whether forbidding metaphors is solving the problem Susan Sontag put to the fore. We conclude that getting rid of metaphors also makes it impossible for patients to use metaphors to feel better. PMID- 22085583 TI - The effect of the diterpene 5-epi-icetexone on the cell cycle of Trypanosoma cruzi. AB - Numerous natural compounds have been used against Trypanosoma cruzi, the causative agent of Chagas' disease. Here, we studied the effect of the diterpene 5-epi-icetexone on growth and morphology of parasites synchronized with hydroxyurea, at different periods of time after removal of the nucleotide. We observed that the diterpene does not affect the growth of the parasites when added within 10 h after removal of hydroxyurea, but the compound was effective on growth when added to the cultures after 12 h. Thymidine incorporation was somewhat inhibited when the diterpene was added at 12 h after removal of hydroxyurea, possibly on the transition S/G2. Using transmission electron microscopy we observed that the diterpene induced a delay in the progression of cell division. We conclude that the compound, at cytostatic dose, affects the cell cycle of T. cruzi, possibly in the transition S/G2 phase and cell division. Further studies will focus to identify the molecular targets for the action of 5 epi-icetexone. PMID- 22085584 TI - Phylogenetic relationships amongst Chloromyxum Mingazzini, 1890 (Myxozoa: Myxosporea), and the description of six novel species from Australian elasmobranchs. AB - Six novel species of Chloromyxum Mingazzini, 1890 are described using a whole evidence approach combining morphometric and molecular data, together with features of their biology. Elasmobranchs were collected in Australian waters, from the Great Barrier Reef, Queensland, off Lizard and Heron Islands; from Moreton Bay, southeast Queensland; off Hobart, Tasmania; and from the Tamar River, Launceston, Tasmania. The novel species proposed here are: Chloromyxum hemiscyllii n.sp. from Hemiscyllium ocellatum; Chloromyxum kuhlii n.sp. from Neotrygon kuhlii; Chloromyxum lesteri n.sp. from Cephaloscyllium laticeps; Chloromyxum mingazzinii n.sp. from Pristiophorus nudipinnis; Chloromyxum myliobati n.sp. from Myliobatis australis; and Chloromyxum squali n.sp. from Squalus acanthias. A seventh species from Squalus acanthias is also reported but due to limited material is not formally described. Molecular phylogenetic analyses revealed that the genus Chloromyxum is polyphyletic, and species from elasmobranchs form a well-supported sister clade, with the type species Chloromyxum leydigi, to all other congeneric species clustering within the freshwater myxosporean clade. Morphological analysis showed that elasmobranch infecting species are predominantly pyriform shaped, have clearly thickened spore apex and possess caudal filaments, compared to other Chloromyxum species which are generally spherical or subspherical, and lack caudal filaments. These morphological and phylogenetic data provide further support for the erection of new genera, but we conservatively consider the species described in this study and other elasmobranch-infecting Chloromyxum species as Chloromyxum sensu strictu, whilst the freshwater teleost infecting and amphibian infecting species we will assign as Chloromyxum sensu lato, until more comprehensive data are available. PMID- 22085585 TI - Team behaviors in emergency care: a qualitative study using behavior analysis of what makes team work. AB - OBJECTIVE: Teamwork has been suggested as a promising approach to improving care processes in emergency departments (ED). However, for teamwork to yield expected results, implementation must involve behavior changes. The aim of this study is to use behavior analysis to qualitatively examine how teamwork plays out in practice and to understand eventual discrepancies between planned and actual behaviors. METHODS: The study was set in a Swedish university hospital ED during the initial phase of implementation of teamwork. The intervention focused on changing the environment and redesigning the work process to enable teamwork. Each team was responsible for entire care episodes, i.e. from patient arrival to discharge from the ED. Data was collected through 3 days of observations structured around an observation scheme. Behavior analysis was used to pinpoint key teamwork behaviors for consistent implementation of teamwork and to analyze the contingencies that decreased or increased the likelihood of these behaviors. RESULTS: We found a great discrepancy between the planned and the observed teamwork processes. 60% of the 44 team patients observed were handled solely by the appointed team members. Only 36% of the observed patient care processes started according to the description in the planned teamwork process, that is, with taking patient history together. Beside this behavior, meeting in a defined team room and communicating with team members were shown to be essential for the consistent implementation of teamwork. Factors that decreased the likelihood of these key behaviors included waiting for other team members or having trouble locating each other. Getting work done without delay and having an overview of the patient care process increased team behaviors. Moreover, explicit instructions on when team members should interact and communicate increased adherence to the planned process. CONCLUSIONS: This study illustrates how behavior analysis can be used to understand discrepancies between planned and observed behaviors. By examining the contextual conditions that may influence behaviors, improvements in implementation strategies can be suggested. Thereby, the adherence to a planned intervention can be improved, and/or revisions of the intervention be suggested. PMID- 22085588 TI - The systemic response to brain injury and disease. AB - The idea that the brain is immunologically privileged and displays an atypical leukocyte recruitment profile following injury has influenced our ideas about how signals might be carried between brain and the periphery. For many, this has encouraged a cerebrocentric view of immunological responses to CNS injury, with little reference to the potential contribution from other organs. However, it is clear that bidirectional pathways between the brain and the peripheral immune system are important in the pathogenesis of CNS disease. In recent years, we have begun to understand the signals that are carried to the periphery and discovered new functions for known chemokines, made by the liver in response to brain injury, as important regulators of the CNS inflammatory response. PMID- 22085587 TI - Long term adequate n-3 polyunsaturated fatty acid diet protects from depressive like behavior but not from working memory disruption and brain cytokine expression in aged mice. AB - Converging epidemiological studies suggest that dietary essential n-3 polyunsaturated fatty acid (PUFA) are likely to be involved in the pathogenesis of mood and cognitive disorders linked to aging. The question arises as to whether the decreased prevalence of these symptoms in the elderly with high n-3 PUFA consumption is also associated with improved central inflammation, i.e. cytokine activation, in the brain. To answer this, we measured memory performance and emotional behavior as well as cytokine synthesis and PUFA level in the spleen and the cortex of adult and aged mice submitted to a diet with an adequate supply of n-3 PUFA in form of alpha-linolenic acid (alpha-LNA) or a n-3 deficient diet. Our results show that docosahexaenoic acid (DHA), the main n-3 PUFA in the brain, was higher in the spleen and cortex of n-3 adequate mice relative to n-3 deficient mice and this difference was maintained throughout life. Interestingly, high level of brain DHA was associated with a decrease in depressive-like symptoms throughout aging. On the opposite, spatial memory was maintained in adult but not in aged n-3 adequate mice relative to n-3 deficient mice. Furthermore, increased interleukin-6 (IL-6) and decreased IL-10 expression were found in the cortex of aged mice independently of the diets. All together, our results suggest that n-3 PUFA dietary supply in the form of alpha-LNA is sufficient to protect from deficits in emotional behavior but not from memory disruption and brain proinflammatory cytokine expression linked to age. PMID- 22085590 TI - A probabilistic risk assessment approach used to prioritize chemical constituents in mainstream smoke of cigarettes sold in China. AB - The chemical and physical complexity of cigarette mainstream smoke (MSS) presents a challenge in the understanding of risk for smoking-related diseases. Quantitative risk assessment is a useful tool for assessing the toxicological risks that may be presented by smoking currently available commercial cigarettes. In this study, yields of a selected group of chemical constituents were quantified in machine-generated MSS from 30 brands of cigarettes sold in China. Using constituent yields, exposure estimates specific to and representative of the Chinese population, and available dose-response data, a Monte Carlo method was applied to simulate probability distributions for incremental lifetime cancer risk (ILCR), hazard quotient (HQ), and margin of exposure (MOE) values for each constituent as appropriate. Measures of central tendency were extracted from the outcome distributions and constituents were ranked according to these three risk assessment indices. The constituents for which ILCR >10(-4), HQ >1, and MOE <10,000 included acetaldehyde, acrylonitrile, benzene, cadmium, formaldehyde, and pyridine. While limitations exist to this methodology in estimating the absolute magnitude of health risk contributed by each MSS constituent, this approach provides a plausible and objective framework for the prioritization of toxicants in cigarette smoke and is valuable in guiding tobacco risk management. PMID- 22085589 TI - Regulatory assessment of in vitro skin corrosion and irritation data within the European framework: Workshop recommendations. AB - Validated in vitro methods for skin corrosion and irritation were adopted by the OECD and by the European Union during the last decade. In the EU, Switzerland and countries adopting the EU legislation, these assays may allow the full replacement of animal testing for identifying and classifying compounds as skin corrosives, skin irritants, and non irritants. In order to develop harmonised recommendations on the use of in vitro data for regulatory assessment purposes within the European framework, a workshop was organized by the Swiss Federal Office of Public Health together with ECVAM and the BfR. It comprised stakeholders from various European countries involved in the process from in vitro testing to the regulatory assessment of in vitro data. Discussions addressed the following questions: (1) the information requirements considered useful for regulatory assessment; (2) the applicability of in vitro skin corrosion data to assign the corrosive subcategories as implemented by the EU Classification, Labelling and Packaging Regulation; (3) the applicability of testing strategies for determining skin corrosion and irritation hazards; and (4) the applicability of the adopted in vitro assays to test mixtures, preparations and dilutions. Overall, a number of agreements and recommendations were achieved in order to clarify and facilitate the assessment and use of in vitro data from regulatory accepted methods, and ultimately help regulators and scientists facing with the new in vitro approaches to evaluate skin irritation and corrosion hazards and risks without animal data. PMID- 22085591 TI - Safety assessment of the commensal strain Bacteroides xylanisolvens DSM 23964. AB - We recently isolated and characterized the new strain Bacteroides xylanisolvens DSM 23964 and presented it as potential candidate for the first natural probiotic strain of the genus Bacteroides. In order to evaluate the safety of this strain for use in food, the following standard toxicity assays were conducted with this strain in both viable and pasteurized form: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration assay, and 90day subchronic repeated oral toxicity studies in mice. No mutagenic, clastogenic, or toxic effects were detected even at extremely high doses. In addition, no clinical, hematological, ophthalmological, or histopathological abnormality could be observed after necropsy at any of the doses tested. Hence, the NOAEL could be estimated to be greater than 2.3*10(11) CFUs, and 2.3*10(14) for pasteurized bacteria calculated as equivalent for an average 70kg human being. In addition, the absence of any in vivo pathogenic properties of viable B. xylanisolvens DSM 23964 cells was confirmed by means of an intraperitoneal abscess formation model in mice which also demonstrated that the bacteria are easily eradicated by the host's immune system. The obtained results support the assumed safety of B. xylanisolvens DSM 23964 for use in food. PMID- 22085592 TI - Targeting microRNAs in neurons: tools and perspectives. AB - In the past few years, the understanding of microRNA (miRNA) biogenesis, the molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has been expanded. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that their post-transcriptional regulation may be particularly relevant in neural development and function. miRNA studies in neurobiology have shown their involvement in synaptic plasticity and brain diseases. Approaches for manipulating miRNA levels in neuronal cells in vitro and in vivo are described here. Recent applications of miRNA antisense oligonucleotides, miRNA gene knockout and miRNA sponges in neuronal cells are reviewed. Finally, miRNA-based therapies for neurological pathologies related to alterations in miRNA functions are discussed. PMID- 22085593 TI - Development of yeast cell factories for consolidated bioprocessing of lignocellulose to bioethanol through cell surface engineering. AB - To build an energy and material secure future, a next generation of renewable fuels produced from lignocellulosic biomass is required. Although lignocellulosic biomass, which represents an abundant, inexpensive and renewable source for bioethanol production, is of great interest as a feedstock, the complicated ethanol production processes involved make the cost of producing bioethanol from it higher compared to corn starch and cane juice. Therefore, consolidated bioprocessing (CBP), which combines enzyme production, saccharification and fermentation in a single step, has gained increased recognition as a potential bioethanol production system. CBP requires a highly engineered microorganism developed for several different process-specific characteristics. The dominant strategy for engineering a CBP biocatalyst is to express multiple components of a cellulolytic system from either fungi or bacteria in the yeast Saccharomyces cerevisiae. The development of recombinant yeast strains displaying cellulases and hemicellulases on the cell surface represents significant progress toward realization of CBP. Regardless of the process used for biomass hydrolysis, CBP enabling microorganisms encounter a variety of toxic compounds produced during biomass pretreatment that inhibit microbial growth and ethanol yield. Systems biology approaches including disruptome screening, transcriptomics, and metabolomics have been recently exploited to gain insight into the molecular and genetic traits involved in tolerance and adaptation to the fermentation inhibitors. In this review, we focus on recent advances in development of yeast strains with both the ability to directly convert lignocellulosic material to ethanol and tolerance in the harsh environments containing toxic compounds in the presence of ethanol. PMID- 22085594 TI - Fabrication of superhydrophobic and antibacterial surface on cotton fabric by doped silica-based sols with nanoparticles of copper. AB - The study discussed the synthesis of silica sol using the sol-gel method, doped with two different amounts of Cu nanoparticles. Cotton fabric samples were impregnated by the prepared sols and then dried and cured. To block hydroxyl groups, some samples were also treated with hexadecyltrimethoxysilane. The average particle size of colloidal silica nanoparticles were measured by the particle size analyzer. The morphology, roughness, and hydrophobic properties of the surface fabricated on cotton samples were analyzed and compared via the scanning electron microscopy, the transmission electron microscopy, the scanning probe microscopy, with static water contact angle (SWC), and water shedding angle measurements. Furthermore, the antibacterial efficiency of samples was quantitatively evaluated using AATCC 100 method. The addition of 0.5% (wt/wt) Cu into silica sol caused the silica nanoparticles to agglomerate in more grape-like clusters on cotton fabrics. Such fabricated surface revealed the highest value of SWC (155 degrees for a 10-MUl droplet) due to air trapping capability of its inclined structure. However, the presence of higher amounts of Cu nanoparticles (2% wt/wt) in silica sol resulted in the most slippery smooth surface on cotton fabrics. All fabricated surfaces containing Cu nanoparticles showed the perfect antibacterial activity against both of gram-negative and gram-positive bacteria. PMID- 22085595 TI - Expression of proinflammatory, proatherogenic genes is reduced by the Mediterranean diet in elderly people. AB - Ageing is an important determinant of atherosclerosis development rate, mainly by the creation of a chronic low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in the fasting and postprandial states. Our aim was to study the effects of dietary fat on the expression of genes related to inflammation (NF-kappaB, monocyte chemoattractant protein 1 (MCP 1), TNF-alpha and IL-6) and plaque stability (matrix metalloproteinase 9, MMP-9) during the postprandial state of twenty healthy, elderly people who followed three diets for 3 weeks each: (1) Mediterranean diet (Med Diet) enriched in MUFA with virgin olive oil; (2) SFA-rich diet; and (3) low-fat, high-carbohydrate diet enriched in n-3 PUFA (CHO-PUFA diet) by a randomised crossover design. At the end of each period, after a 12-h fast, the subjects received a breakfast with a composition similar to the one when the dietary period ended. In the fasting state, the Med Diet consumption induced a lower gene expression of the p65 subunit of NF-kappaB compared with the SFA-rich diet (P = 0.019). The ingestion of the Med Diet induced a lower gene postprandial expression of p65 (P = 0.033), MCP-1 (P = 0.0229) and MMP-9 (P = 0.041) compared with the SFA-rich diet, and a lower gene postprandial expression of p65 (P = 0.027) and TNF-alpha (P = 0.047) compared with the CHO-PUFA diet. Direct plasma quantification mostly reproduced the findings. Our data suggest that consumption of a Med Diet reduces the postprandial inflammatory response in mononuclear cells compared with the SFA rich and CHO-PUFA diets in elderly people. These findings may be partly responsible for the lower CVD risk found in populations with a high adherence to the Med Diet. PMID- 22085597 TI - Detection of changes in luminance distributions. AB - How well can observers detect the presence of a change in luminance distributions? Performance was measured in three experiments. Observers viewed pairs of grayscale images on a calibrated CRT display. Each image was a checkerboard. All luminances in one image of each pair consisted of random draws from a single probability distribution. For the other image, some patch luminances consisted of random draws from that same distribution, while the rest of the patch luminances (test patches) consisted of random draws from a second distribution. The observers' task was to pick the image with luminances drawn from two distributions. The parameters of the second distribution that led to 75% correct performance were determined across manipulations of (1) the number of test patches, (2) the observers' certainty about test patch location, and (3) the geometric structure of the images. Performance improved with number of test patches and location certainty. The geometric manipulations did not affect performance. An ideal observer model with high efficiency fit the data well and a classification image analysis showed a similar use of information by the ideal and human observers, indicating that observers can make effective use of photometric information in our distribution discrimination task. PMID- 22085598 TI - It is time to consider third-line options in antiretroviral-experienced paediatric patients? AB - BACKGROUND: The historic use of full-dose ritonavir as part of an unboosted protease inhibitor (PI)-based antiretroviral therapy regimen in some South African children contributes to the frequent accumulation of major PI resistance mutations. METHODS: In order to describe the prevalence of major PI resistance in children failing antiretroviral therapy and to investigate the clinical, immunological and virological outcomes in children with PI resistance, we conducted a cross-sectional study, with a nested case series, following up those children with major PI resistance. The setting was public health sector antiretroviral clinics in the Western Cape province of South Africa, and the subjects were children failing antiretroviral therapy. The following outcome measures were investigated: CD4 count, viral load and resistance mutations. RESULTS: Fourteen (17%) of 82 patients, referred from tertiary hospitals, had major PI resistance. All these patients were exposed to regimens that included ritonavir as a single PI. Immune reconstitution and clinical benefit were achieved when using a lopinavir/ritonavir-based treatment regimen in these children with prior PI resistance. At first HIV-1 viral load follow up after initial resistance testing (n = 11), only one patient had a viral load of less than 400 copies/ml; at a subsequent follow up (n = 9), the viral loads of five patients were less than 400 copies/ml. Patients retained on LPV/r had lower viral loads than those switched to a non-nucleoside reverse transcriptase inhibitor (NNRTI). However, two of three patients with follow-up resistance tests accumulated additional PI resistance. CONCLUSIONS: In children with pre-existing PI resistance, although initially effective, the long-term durability of a lopinavir/ritonavir-based treatment regimen can be compromised by the accumulation of resistance mutations. Furthermore, a second-line NNRTI regimen is often not durable in these patients. As genotypic resistance testing and third line treatment regimens are costly and limited in availability, we propose eligibility criteria to identify patients with high risk for resistance and guidance on drug selection for children who would benefit from third-line therapy. PMID- 22085599 TI - Measles genotypes D4 and G3 reintroduced by multiple foci after 15 years without measles virus circulation, Gipuzkoa, the Basque Country, Spain, March to June 2011. AB - During a three-month period in spring 2011, 23 cases of measles occurred in seven independent outbreaks in a region in Spain with around 700,000 inhabitants, where the disease had been eliminated since 1997. High vaccination coverage and rapid diagnosis allowed implementation of containment measures and this prevented spread of the disease. Except for the first outbreak which affected 10 cases, each of the other six outbreaks caused a maximum of three secondary cases. PMID- 22085600 TI - Human case of autochthonous West Nile virus lineage 2 infection in Italy, September 2011. AB - On 10 September 2011, a patient in his 50s was admitted to hospital in Ancona, Italy, after six days of high fever and no response to antibiotics. West Nile virus (WNV) infection was suspected after tests to determine the aetiology of the fever were inconclusive. On 20 September, WNV-specific IgM and IgG antibodies were detected in the patient's serum. Genomic sequencing of the viral isolate showed that the virus belonged to WNV lineage 2. PMID- 22085601 TI - First Neisseria gonorrhoeae strain with resistance to cefixime causing gonorrhoea treatment failure in Austria, 2011. AB - We describe the first cefixime-resistant Neisseria gonorrhoeae strain in Austria that caused treatment failure.It follows the first five cases in Europe of cefixime treatment failure, reported in Norway in 2010 and the United Kingdom in 2011. Effective treatment of gonorrhoea is crucial for public health control and, at present, requires substantially enhanced awareness, more frequent test-of cure, interaction with experts after therapeutic failure, tracing and therapy of contacts, and surveillance of gonococcal antimicrobial resistance and treatment failures worldwide. PMID- 22085602 TI - Highly heterogeneous temperature sensitivity of 2009 pandemic influenza A(H1N1) viral isolates, northern France. AB - We assayed the temperature sensitivity of 2009 pandemic influenza A(H1N1) viral isolates (n=23) and seasonal influenza A(H1N1) viruses (n=18) isolated in northern France in 2007/08 and 2008/09. All isolates replicated with a similar efficiency at 34 degrees C and 37 degrees C, and with a lower efficiency at 40 degrees C. The pandemic viral isolates showed a stronger heterogeneity in their ability to grow at the highest temperature, as compared with the seasonal isolates. No statistically significant difference in temperature sensitivity was observed between the pandemic viral isolates from severe and mild cases of influenza. Our data point to the impact of temperature sensitivity on the genetic evolution and diversification of the pandemic influenza A(H1N1) virus since its introduction into the human population in April 2009, and call for close surveillance of this phenotypic marker related to host and tissue tropism. PMID- 22085603 TI - Nosocomial and non-nosocomial Clostridium difficile infections in hospitalised patients in Belgium: compulsory surveillance data from 2008 to 2010. AB - Surveillance of Clostridium difficile infection (CDI) is compulsory in Belgian hospitals. Our objectives were to compare incidence and case characteristics of nosocomial infections (Nc-CDI) with onset of diarrhoea more than two days after hospital admission, with non-nosocomial cases (Nnc-CDI). The database included inpatients from 2008 to 2010. Of 8,351 cases reported by 150 hospitals, 3,102 (37%) were classified as Nnc-CDI and 5,249 (63%) as Nc-CDI. In 2010, the mean incidence per 1,000 admissions was 0.95 for Nc-CDI and 0.56 for Nnc-CDI. Both incidences were relatively stable over the three years, with a slight decrease in 2010 (p<0.01). Onset of symptoms in Nnc- CDI cases took place in the community (57.1%), nursing homes (14.2%) or hospitals (17.5%); data for 11.2%were missing. Nnc-CDI cases were younger than Nc-CDI (median age 75 vs. 79 years, p<0.001), and more likely to be women (62% vs. 57%, p<0.001) and to have pseudomembranous colitis (5.3% vs. 1.6%, p<0.001). In 2009, C. difficile ribotype 027 was found in 32 of 70 reporting hospitals compared with 19 of 69 in 2010 (p<0.03). Although our study population only included hospitalised patients, the results do not support the hypothesis of an increase in the incidence of severe community associated CDI. PMID- 22085605 TI - Globotriaosylceramide is correlated with oxidative stress and inflammation in Fabry patients treated with enzyme replacement therapy. AB - Fabry disease is an X-linked inborn error of glycosphingolipid catabolism due to deficient activity of alpha-galactosidase A that leads to accumulation of the enzyme substrates, mainly globotriaosylceramide (Gb3), in body fluids and lysosomes of many cell types. Some pathophysiology hypotheses are intimately linked to reactive species production and inflammation, but until this moment there is no in vivo study about it. Hence, the aim of this study was to investigate oxidative stress parameters, pro-inflammatory cytokines and Gb3 levels in Fabry patients under treatment with enzyme replacement therapy (ERT) and finally to establish a possible relation between them. We analyzed urine and blood samples of patients under ERT (n=14) and healthy age-matched controls (n=14). Patients presented decreased levels of antioxidant defenses, assessed by reduced glutathione (GSH), glutathione peroxidase (GPx) activity and increased superoxide dismutase/catalase (SOD/CAT) ratio in erythrocytes. Concerning to the damage to biomolecules (lipids and proteins), we found that plasma levels of malondialdehyde (MDA) and protein carbonyl groups and di-tyrosine (di-Tyr) in urine were increased in patients. The pro-inflammatory cytokines IL-6 and TNF alpha were also increased in patients. Urinary Gb3 levels were positively correlated with the plasma levels of IL-6, carbonyl groups and MDA. IL-6 levels were directly correlated with di-Tyr and inversely correlated with GPx activity. This data suggest that pro-inflammatory and pro-oxidant states occur, are correlated and seem to be induced by Gb3 in Fabry patients. PMID- 22085606 TI - Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. AB - Serious concerns have been expressed about potential risks of engineered nanoparticles. Regulatory health risk assessment of such particles has become mandatory for the safe use of nanomaterials in consumer products and medicines; including the potential effects on reproduction and fertility, are relevant for this risk evaluation. In this study, we examined effects of silver particles of nano- (20nm) and submicron- (200nm) size, and titanium dioxide nanoparticles (TiO(2)-NPs; 21nm), with emphasis on reproductive cellular- and genotoxicity. Ntera2 (NT2, human testicular embryonic carcinoma cell line), and primary testicular cells from C57BL6 mice of wild type (WT) and 8-oxoguanine DNA glycosylase knock-out (KO, mOgg1(-/-)) genotype were exposed to the particles. The latter mimics the repair status of human testicular cells vs oxidative damage and is thus a suitable model for human male reproductive toxicity studies. The results suggest that silver nano- and submicron-particles (AgNPs) are more cytotoxic and cytostatic compared to TiO(2)-NPs, causing apoptosis, necrosis and decreased proliferation in a concentration- and time-dependent manner. The 200nm AgNPs in particular appeared to cause a concentration-dependent increase in DNA strand breaks in NT2 cells, whereas the latter response did not seem to occur with respect to oxidative purine base damage analysed with any of the particles tested. PMID- 22085607 TI - Manganese accumulation in nail clippings as a biomarker of welding fume exposure and neurotoxicity. AB - Occupational exposure to welding fumes (WF) is thought to cause Parkinson's disease (PD)-like neurological dysfunction. An apprehension that WF may accelerate the onset of PD also exists. Identifying reliable biomarkers of exposure and neurotoxicity are therefore critical for biomonitoring and neurological risk characterization of WF exposure. Manganese (Mn) in welding consumables is considered the causative factor for the neurological deficits seen in welders. Hence, we sought to determine if Mn accumulation in blood or nail clippings can be a marker for adverse exposure and neurotoxicity. To model this, rats were exposed by intratracheal instillation to dissolved or suspended fume components collected from gas metal arc-mild steel (GMA-MS) or manual metal arc hard surfacing (MMA-HS) welding. Trace element analysis revealed selective Mn accumulation in dopaminergic brain areas, striatum (STR) and midbrain (MB), following exposure to the two fumes. This caused dopaminergic abnormality as evidenced by loss of striatal tyrosine hydroxylase (Th; 25-32% decrease) and Parkinson disease (autosomal recessive, early onset) 7 (Park7; 25-46% decrease) proteins. While blood Mn was not detectable, Mn levels in nails strongly correlated with the pattern of Mn accumulation in the striatum (R(2)=0.9386) and midbrain (R(2)=0.9332). Exposure to manganese chloride (MnCl(2)) caused similar Mn accumulation in STR, MB and nail. Our findings suggest that nail Mn has the potential to be a sensitive and reliable biomarker for long-term Mn exposure and associated neurotoxicity. The non-invasive means by which nail clippings can be collected, stored, and transported with relative ease, make it an attractive surrogate for biomonitoring WF exposures in occupational settings. PMID- 22085608 TI - iTRAQ-based proteomic profiling of human serum reveals down-regulation of platelet basic protein and apolipoprotein B100 in patients with hematotoxicity induced by chronic occupational benzene exposure. AB - Benzene is an important industrial chemical and an environmental contaminant, but the pathogenesis of hematotoxicity induced by chronic occupational benzene exposure (HCOBE) remains to be elucidated. To gain an insight into the molecular mechanisms and developmental biomarkers for HCOBE, isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS) were utilized. Identification and quantitation of differentially expressed proteins between HCOBE cases and healthy control were thus made. Expressions of selected proteins were confirmed by western blot and further validated by ELISA. A total of 159 unique proteins were identified (>=95% confidence), and relative expression data were obtained for 141 of these in 3 iTRAQ experiments, with fifty proteins found to be in common among 3 iTRAQ experiments. Plasminogen (PLG) was found to be significantly up regulated, whereas platelet basic protein (PBP) and apolipoprotein B100 (APOB100) were significantly down-regulated in the serum of HCOBE cases. Additionally, the altered proteins were associated with the molecular functions of binding, catalytic activity, enzyme regulator activity and transporter activity, and involved in biological processes of apoptosis, developmental and immune system process, as well as response to stimulus. Furthermore, differential expressions of PLG, PBP and APOB100 were confirmed by western blot, and the clinical relevance of PBP and APOB100 with HCOBE was validated by ELISA. Overall, our results showed that lowered expression of PBP and APOB100 proteins served as potential biomarkers of HCOBE, and may play roles in the benzene-induced immunosuppressive effects and disorders in lipid metabolism. PMID- 22085611 TI - Stepping to stability and fall prevention in adult psychiatric patients. AB - Fall prevention is a major area of concern in inpatient settings. This article reports on the feasibility of implementing a daily exercise program that features line dancing to promote stability, balance, and flexibility in adult psychiatric patients and describes the impact of that program. Six hundred sixty-five patient charts drawn from before and after the practice change were reviewed. The fall rate after the introduction of line dancing was 2.8% compared with 3.2% before implementation. In a setting that treats both men and women of many ages and with varying levels of mobility, line dancing offers a viable approach to exercise in a secure setting. PMID- 22085609 TI - Temperature-dependent structural and functional properties of a mutant (F71L) alphaA-crystallin: molecular basis for early onset of age-related cataract. AB - Previously we identified a novel mutation (F71L) in the alphaA-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not significantly different from wild-type with regard to secondary and tertiary structural organization, hydrophobicity and the apparent molecular mass of oligomer but has substantial differences in structural and functional properties following a heat treatment. Wild-type alphaA-crystallin demonstrated increased CLA, whereas the F71L-mutant substantially lost its CLA upon heat treatment. Further, unlike the wild-type alphaA-subunit, F71L-subunit did not protect the alphaB-subunit in hetero-oligomeric complex from heat-induced aggregation. Moreover, hetero oligomer containing F71L and alphaB in 3:1 ratio had significantly lower CLA upon thermal treatment compared to its unheated control. These results indicate that alpha-crystallin complexes containing F71L-alphaA subunits are less stable and have reduced CLA. Therefore, F71L may lead to earlier onset of cataract due to interaction with several environmental factors (e.g., temperature in this case) along with the aging process. PMID- 22085612 TI - The role of psychiatric nurse faculty in establishing a campus suicide prevention program. AB - Suicide among college students has received increased national attention over the past few decades, partly due to the publicity regarding high-profile suicide events on college campuses throughout the United States and its territories. Currently, suicide is identified as the second-leading cause of death in college students. Due to federal legislation such as the Garrett Lee Smith Memorial Act of 2004, many college campuses have been able to establish suicide prevention programs. This article describes how a psychiatric nurse faculty member successfully established a comprehensive suicide prevention program that was initially supported by grant funds from the Garrett Lee Smith Memorial Act. PMID- 22085613 TI - Update on energy drinks and youth. AB - Energy drinks are attractive and readily available in every grocery store and gas station. While most youth verbalize an understanding that too much caffeine is bad for one's health, at an age of multiple demands, an over-the-counter offer of increased energy and alertness is hard to ignore. What makes energy drinks different from regular coffee? Although the heavily caffeinated drinks promise increased energy and stamina and are loaded with healthy natural ingredients, excessive consumption is of concern on many levels. This article will discuss some of the effects of excessive caffeine, as well as risks associated with energy drinks mixed with alcohol. PMID- 22085614 TI - A critical evaluation of the cardiac toxicity of citalopram: part 2. AB - In August 2011, the U.S. Food and Drug Administration issued a drug safety communication that the antidepressant drug citalopram (Celexa(r)) should not be used at dosages greater than 40 mg per day (or greater than 20 mg per day for patients 60 and older) because higher doses have been associated with abnormal heart rhythms. Clinical studies using citalopram in patients with cardiac disease and in older patients do not confirm such a risk. The major metabolite of citalopram is demethylcitalopram, which is subsequently metabolized to the minor metabolite didemethylcitalopram (DDCT). High DDCT concentrations have been associated with QT interval prolongation in beagle dogs. Therapeutic drug monitoring study data suggest that routine or even high oral doses of citalopram are unlikely to result in cardiotoxic concentrations of the DDCT metabolite. Based on evidence taken from a wide variety of studies, the citalopram dose limitations described in the safety announcement do not have strong clinical justification. PMID- 22085615 TI - Debunking misconceptions about weight loss surgery. AB - The recent and steady rise in the U.S. obesity index has resulted in a consumer driven market for more effective treatment interventions for the morbidly obese population. Given the relatively poor outcomes associated with traditional approaches for treating obesity, such as diet programs, behavioral modification, and pharmacotherapy, weight loss surgical procedures represent a safe and effective option for those who meet selection criteria. To provide optimal treatment and consumer education, psychiatric nurses need to be well informed about the psychological and physiological aspects of these surgical procedures. This article clarifies six common misconceptions related to weight loss surgery. PMID- 22085616 TI - Influence of broccoli extract and various essential oils on performance and expression of xenobiotic- and antioxidant enzymes in broiler chickens. AB - The aim of our present study was to examine the regulation of xenobiotic- and antioxidant enzymes by phytogenic feed additives in the intestine and the liver of broilers. A total of 240 male Ross-308 broiler chickens (1 d old) were fed a commercial starter diet for 2 weeks. On day 15, the birds were assigned to six treatment groups of forty birds each. The control (Con) group was fed a diet without any additive for 3 weeks. The diet of group sulforaphane (SFN) contained broccoli extract providing 0.075 g/kg SFN, whereas the diets of the other four groups contained 0.15 g/kg essential oils from turmeric (Cuo), oregano (Oo), thyme and rosemary (Ro). Weight gain and feed conversion were slightly impaired by Cuo and Oo. In the jejunum SFN, Cuo and Ro increased the expression of xenobiotic enzymes (epoxide hydrolases 1 and 2 and aflatoxin B1 aldehyde reductase) and of the antioxidant enzyme haeme oxygenase regulated by an 'antioxidant response element' (ARE) compared to group Con. In contrast to our expectations in the liver, the expression of these enzymes was decreased by all the additives. Nevertheless, all the additives increased the Trolox equivalent antioxidant capacity of the jejunum and the liver and reduced Fe-induced lipid peroxidation in the liver. We conclude that the up-regulation of ARE genes in the small intestine reduces oxidative stress in the organism and represents a novel mechanism by which phytogenic feed additives improve the health of farm animals. PMID- 22085617 TI - Concurrent radiotherapy and chemotherapy for locally advanced squamous cell carcinoma of the head and neck. AB - BACKGROUND: Concurrent chemoradiation is the standard treatment for patients with advanced head and neck squamous cell carcinoma (HNSCC).The present study was carried out to assess the feasibility and efficacy of low-dose gemcitabine as a radiosensitizer when used during radical therapeutic management of patients with locally advanced HNSCC. PATIENTS AND METHODS: Fifty-two patients with locally advanced HNSCC (stage III, 50%; stage IVa, 50%) were enrolled during the period from July 2008 to December 2010. All received a course of radiotherapy (70 Gy over 7 weeks) concurrent with weekly infusions of gemcitabine at 50 mg/m(2). RESULTS: All patients were available for toxicity and response. Severe mucositis (grade 3-4) was observed in 76% of patients. Severe hematological toxicity was uncommon. Xerostomia was the most common late toxicity in 34 patients (65.4%). The rate of complete and partial response rate was 67.3% and 21.1%, respectively, with an overall response rate of 88.45%. Two years progression-free survival and disease-free survival were 46% and 38.46%, respectively. CONCLUSION: Using low dose gemcitabine concurrent with radiotherapy maintains high response rate with low systemic toxicity, in spite of severe mucositis in a high percentage of patients. PMID- 22085618 TI - Outbreak of Shigella sonnei infection in Norway linked to consumption of fresh basil, October 2011. AB - We report a Shigella sonnei outbreak of 46 cases that occurred in Norway during October 2011. Two municipalities were involved. A large cluster (42 cases)was concentrated in north Norway, while a smallcluster (4 cases) occurred in the south-east region.Epidemiological evidence and trace back investigations have linked the outbreak to the consumption of imported fresh basil. The product has been withdrawn from the market. No further cases have been reported since 25 October. PMID- 22085619 TI - Case report: tick-borne encephalitis in two Dutch travellers returning from Austria, Netherlands, July and August 2011. AB - Tick-borne encephalitis (TBE) is not endemic in the Netherlands and diagnostics are seldom requested. Here, we report about the rare event of TBE in two Dutch travellers returning from Austria in July and August 2011. This report serves to create awareness among physicians to consider travel-related TBE in their differential diagnosis of patients with neurological disease returning from TBE virus endemic regions and to promote awareness among professionals advising travellers. PMID- 22085620 TI - Seroprevalence of herpes simplex virus type 1 and type 2 in Thuringia, Germany, 1999 to 2006. AB - The prevalence of herpes simplex virus (HSV) type-specific IgG was determined in sera taken in 1999 to 2006 from 1,100 children aged 0-18 years, 800 blood donors and 200 pregnant women in Thuringia, Germany, using tests based on the HSV glycoproteins (g) gG. By the age of 10-12 years, HSV-1 IgG prevalence reached 57.3%, rising to 69.3% by the age of 16-18 years and to 78.0% by the age of 28-30 years. Between 2.7% and 4.7% of the children aged up to 15 years had HSV-2 antibodies, increasing to 7.3% at the age of 16-18 years and to 13.6% among adults. The prevalence of HSV-1 antibodies among girls was significantly lower than among boys and a significantly higher prevalence of HSV-2 IgG in women than in men was detected. The reduced incidence of HSV-1 infections during childhood, especially in girls, has to be followed up since a higher number of primary HSV-2 infections may result. Between 2.7% and 4.7% of all children tested seemed to acquire HSV-2 by intrauterine or neonatal infection. We also compared the use of gG-1 with gC-1: the agreement of 97.2% between the two ELISAs suggests that gG-1 and gC-1 can be considered equivalent antigenic targets. PMID- 22085621 TI - Influenza surveillance during the post-pandemic influenza 2010/11 season in Greece, 04 October 2010 to 22 May 2011. AB - In this manuscript, we summarise the experience of Greece during the post pandemic influenza season 2010/11 from 04 October 2010 to 22 May 2011. The spread of the disease and its impact were monitored using multiple surveillance systems, such as sentinel surveillance, virological surveillance and all-cause mortality surveillance. We also focus on the characteristics of laboratory-confirmed severe influenza cases who required admission to an intensive care unit (ICU) (n=368), and/or with a fatal outcome (n=180). The influenza-like illness rate reported from sentinel surveillance started rising in early January 2011 and peaked between 31 January and 6 February 2011. The total number of ICU admissions was higher in the post-pandemic influenza season than during the pandemic period causing a lot of pressure on ICUs. The overall population mortality rate due to influenza A(H1N1)2009 was higher than during the pandemic period (15.9 vs 13.2 fatal cases per million, p=0.087). Our data suggest that the severity of clinical illness in the first post-pandemic influenza season was comparable or even higher than during the pandemic. PMID- 22085623 TI - The implications of the new paradigm of dental caries. AB - The caries process is the ubiquitous, natural metabolism in the biofilm that causes numerous fluctuations in pH. The interaction of this biofilm with the dental tissues may result in a caries lesion. However, lesion formation and progression can be controlled, particularly by disturbing plaque regularly with a fluoride containing toothpaste. This paradigm implies that everyone with teeth is at risk to lesion development. Treatment of caries is principally non-operative, involving plaque control, fluoride and a sensible diet. Operative dentistry repairs un-cleansable cavities and is part of plaque control. A diagnosis is a mental resting place on the way to a treatment decision. The relevant diagnostic features with respect to caries are lesion activity (active lesions require active management) and un-cleansable cavities. When teaching undergraduates, it is important that they are credited for the non-operative treatment of caries as well as for operative dentistry. This is equally important in dental practice where an appropriate skills mix of the dental team is required to deliver dental health cost-effectively. Training more dentists may be an expensive mistake as far as disease control is concerned. It is ironic that dentists make most money from operative care and specialist treatment when disease control could be delivered relatively cheaply. The key to dental health is regular and effective plaque control with a fluoride containing toothpaste, from cradle to grave. PMID- 22085624 TI - Mitochondrial energetics in liver and skeletal muscle after energy restriction in young rats. AB - The present study investigated the effect of 2 weeks of energy restriction on whole body, liver and skeletal muscle energy handling. We measured whole-body oxygen consumption, as well as mitochondrial protein mass, respiratory capacity and energetic coupling in liver and skeletal muscle from food-restricted (FR) rats, age- and weight-matched controls. We also assessed markers of oxidative damage and antioxidant defences. The present results show that, in response to energy restriction, an adaptive decrease in whole-body energy expenditure is coupled with structural and functional changes in mitochondrial compartment, both in liver and skeletal muscle. In fact, liver mitochondrial mass per g of liver significantly increased, whereas total hepatic mitochondrial oxidative capacity was lower in FR than in control rats, because of a significant decrease in liver contribution to total body weight. In skeletal muscle, sub-sarcolemmal (SS) mitochondrial respiratory capacity, as well as SS and inter-myofibrillar (IMF) mitochondrial protein mass per g of tissue, was significantly lower in FR rats, compared to controls. Finally, a decrease in oxidative damage was found in liver but not in skeletal muscle mitochondria from FR rats, whereas an increase in antioxidant defence was found in both tissues. From the present results, it appears that skeletal muscle is involved in the decrease in energy expenditure induced by energy restriction. Energy sparing is achieved through changes in the activity (SS), mass (SS and IMF) and efficiency (IMF) of mitochondrial compartment. PMID- 22085625 TI - A replication study examining novel common single nucleotide polymorphisms identified through a prostate cancer genome-wide association study in a Japanese population. AB - Five novel prostate cancer risk loci were identified in a recent genome-wide association study (GWAS) of Japanese persons (Takata et al., Nat Genet. 2010;42(9):751-754). Those authors proposed that apart from population-specific linkage disequilibrium patterns, limitations of GWAS single nucleotide polymorphism (SNP) prioritization and/or study design could explain the lack of identification of these loci in GWAS previously conducted among Caucasians. Thus, the authors undertook a replication study in 1,357 prostate cancer patients and 1,403 healthy Australian males of European descent (2004-2008). The rs12653946 SNP at 5p15 was found to be significantly associated with prostate cancer risk (odds ratio = 1.20, 95% confidence interval: 1.07, 1.34; P = 0.002). On the basis of linkage disequilibrium calculations, the rs12653946 SNP represents an independent locus, distinct from the previously identified TERT-CLPTM1L cancer nexus region. Further, analysis from AceView (Thierry-Mieg and Thierry-Mieg, Genome Biol. 2006;7(suppl 1):S12) indicated that rs12653946 falls within the intron of a testis-expressed gene strongly predicted to translate a conceptual 8.1-kilodalton protein named tojy.aApr07. The authors' findings suggest that follow-up of apparently ethnicity-specific risk associations are warranted in order to highlight risk-associated loci for experimental studies and for incorporation into future risk prediction models for prostate cancer. PMID- 22085626 TI - Apples and oranges? Interpretations of risk adjustment and instrumental variable estimates of intended treatment effects using observational data. AB - Instrumental variable (IV) and risk adjustment (RA) estimators, including propensity score adjustments, are both used to alleviate confounding problems in nonexperimental studies on treatment effects, but it is not clear how estimates based on these 2 approaches compare. Methodological considerations have shown that IV and RA estimators yield estimates of distinct types of causal treatment effects regardless of confounding problems. Many investigators have neglected these distinctions. In this paper, the authors use 3 schematic models to explain visually the relations between IV and RA estimates of intended treatment effects as demonstrated in the methodological studies. When treatment effects are homogeneous across a study population or when treatment effects are heterogeneous across the study population but treatment decisions are unrelated to the treatment effects, RA and IV estimates should be equivalent when the respective assumptions are met. In contrast, when treatment effects are heterogeneous and treatment decisions are related to the treatment effects, RA estimates of treatment effect can asymptotically differ from IV estimates, but both are correct even when the respective assumptions are met. Appropriate interpretations of IV or RA estimates can be facilitated by developing conceptual models related to treatment choice and treatment effect heterogeneity prior to analyses. PMID- 22085627 TI - Re: "Sex-steroid hormones and electrocardiographic QT-interval duration: findings from the Third National Health and Nutrition Examination Survey and the Multi Ethnic Study of Atherosclerosis". PMID- 22085628 TI - Secular trends in Helicobacter pylori seroprevalence in adults in the United States: evidence for sustained race/ethnic disparities. AB - Helicobacter pylori seroprevalence levels in US adults participating in the continuous National Health and Nutrition Examination Survey (1999-2000) increased with age in all racial/ethnic groups, with significantly higher age-standardized levels in Mexican Americans (64.0%, 95% confidence interval (CI): 58.8, 69.2) and non-Hispanic blacks (52.0%, 95% CI: 48.3, 55.7) compared with non-Hispanic whites (21.2%, 95% CI: 19.1, 23.2). Although seroprevalence levels remained similar to those found in National Health and Nutrition Examination Surveys from 1988 to 1991 among non-Hispanic blacks and Mexican Americans, they were significantly lower in non-Hispanic whites, especially at older ages. The factors driving the decline in H. pylori seroprevalence appear to be acting preferentially on the non Hispanic white population. PMID- 22085629 TI - Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Greece. AB - BACKGROUND: Inheritance of a mutation in either BRCA1 or BRCA2 accounts for approximately 5% of all breast cancer cases, but varies by country. Investigations into the contribution of BRCA mutations to breast cancer incidence in Greece have been, for the most part, limited by small sample sizes and by the use of cases selected for their family history of cancer. The aim of the current study was to estimate BRCA mutation frequencies in breast cancer patients unselected for family history. METHODS: To do so, we enrolled 127 unselected women with breast cancer from the Alexandra Hospital in Athens, Greece, a large public hospital in the city. Mutations in BRCA1 and BRCA2 were detected using a combination of techniques and were confirmed by direct sequencing. Two large genomic deletions were sought using mutation-specific assays. A detailed family history of cancer was obtained from each patient. RESULTS: We were able to successfully complete testing on samples from 127 women. Among these, six mutations were identified (four in BRCA1 and two in BRCA2) representing 4.7% of the total or 9.5% of cases diagnosed before age forty. None of the mutation carriers had a family history of breast or ovarian cancer. Three of the four BRCA1 mutations were in exon 20: two were a G5331A mutation and the third was a 3.2 kb deletion. The fourth BRCA1 mutation was the 3819delGTAAA in exon 11. The two BRCA2 mutations were in exon 11 (3782del10 and 4512insT). CONCLUSIONS: The G5331A mutation in BRCA1 appears to be a founder mutation in the Greek population. PMID- 22085630 TI - Features of cadmium and calcium uptake and toxicity in rainbow trout (Oncorhynchus mykiss) mitochondria. AB - Molecular features of cadmium (Cd) and calcium (Ca) uptake and toxicity in rainbow trout liver mitochondria were studied using modulators of mitochondrial permeability transition pore (MPTP), mitochondrial calcium uniporter (MCU) and rapid uptake mode (RaM). Malate-glutamate energized mitochondria were exposed to 20MUM Cd and 50MUM Ca, singly and in combination, with and without addition of ruthenium red (RR), cyclosporin A (CsA), bongkrekic acid (BKA) or dithiothreitol (DTT). State 3 mitochondrial respiration was inhibited by 50% by either Cd or Ca, and by 70% when the two cations were added simultaneously. All the modulators tested reduced the inhibition of state 3 respiration with DTT completely reversing the Cd effect. While state 4 respiration was unaffected by Ca and/or Cd, 1.5-3 fold stimulation was observed on addition of the modulators. Uncoupler stimulated respiration was inhibited by Cd, Ca and Cd+Ca with complete (DTT) and partial (RR, CsA, BKA) protection of the Cd and Cd+Ca effects. All the modulators completely reversed the Ca-induced inhibition. Swelling, the hallmark of MPTP, measured following incubation of mitochondria with 0-100MUM of the two cations, singly and in combination, was abolished by all the modulators. Overall these data show the existence of membrane channels in rainbow trout liver mitochondria with some characteristics similar to mammalian MPTP, MCU and RaM. Moreover, entry of Ca and Cd into mitochondria is important in the toxicity of these cations. PMID- 22085631 TI - Presenting features and long-term effects of growth hormone treatment of children with optic nerve hypoplasia/septo-optic dysplasia. AB - BACKGROUND: Optic nerve hypoplasia (ONH) with/or without septo-optic dysplasia (SOD) is a known concomitant of congenital growth hormone deficiency (CGHD). METHODS: Demographic and longitudinal data from KIGS, the Pfizer International Growth Database, were compared between 395 subjects with ONH/SOD and CGHD and 158 controls with CGHD without midline pathology. RESULTS: ONH/SOD subjects had higher birth length/weight, and mid-parental height SDS. At GH start, height, weight, and BMI SDS were higher in the ONH/SOD group. After 1 year of GH, both groups showed similar changes in height SDS, while weight and BMI SDS remained higher in the ONH/SOD group. The initial height responses of the two groups were similar to those predicted using the KIGS-derived prediction model for children with idiopathic GHD. At near-adult height, ONH/SOD and controls had similar height, weight, and BMI SDS. CONCLUSIONS: Compared to children with CGHD without midline defects, those with ONH/SOD presented with greater height, weight, and BMI SDS. These differences persisted at 1 year of GH therapy, but appeared to be overcome by long-term GH treatment. PMID- 22085632 TI - Chitosan-based therapeutic nanoparticles for combination gene therapy and gene silencing of in vitro cell lines relevant to type 2 diabetes. AB - Glucagon like peptide 1 (GLP-1), a blood glucose homeostasis modulating incretin, has been proposed for the treatment of type 2 diabetes mellitus (T2DM). However, native GLP-1 pharmacokinetics reveals low bioavailability due to degradation by the ubiquitous dipeptydil peptidase IV (DPP-IV) endoprotease. In this study, the glucosamine-based polymer chitosan was used as a cationic polymer-based in vitro delivery system for GLP-1, DPP-IV resistant GLP-1 analogues and siRNA targeting DPP-IV mRNA. We found chitosans to form spherical nanocomplexes with these nucleic acids, generating two distinct non-overlapping size ranges of 141-283 nm and 68-129 nm for plasmid and siRNA, respectively. The low molecular weight high DDA chitosan 92-10-5 (degree of deacetylation, molecular weight and N:P ratio (DDA-Mn-N:P)) showed the highest plasmid DNA transfection efficiency in HepG2 and Caco-2 cell lines when compared to 80-10-10 and 80-80-5 chitosans. Recombinant native GLP-1 protein levels in media of transfected cells reached 23 ng/L while our DPP-IV resistant analogues resulted in a fivefold increase of GLP-1 protein levels (115 ng/L) relative to native GLP-1, and equivalent to the Lipofectamine positive control. We also found that all chitosan-DPP-IV siRNA nanocomplexes were capable of DPP-IV silencing, with 92-10-5 being significantly more effective in abrogating enzymatic activity of DPP-IV in media of silenced cells, and with no apparent cytotoxicity. These results indicate that specific chitosan formulations may be effectively used for the delivery of plasmid DNA and siRNA in a combination therapy of type 2 diabetes. PMID- 22085634 TI - Nonlinear pharmacokinetics of visnagin in rats after intravenous bolus administration. AB - Ammi visnaga L. (syn. Khella, Apiaceae) preparations have traditionally been used in the Middle East for the treatment of kidney stone disease. Visnagin, a furanocoumarin derivative, is one of the main compounds of Ammi visnaga with potential effects on kidney stone prevention. To date, no information is available about the pharmacokinetic (PK) properties of visnagin. It was the aim of the study to characterize the PK properties of visnagin after intravenous (i.v.) bolus administration in rats and to develop an adequate model for the description of the observed data, including model parameter estimates. Therefore, three doses of visnagin (1.25, 2.5, and 5mg/kg) solubilized in 25% Captisol(r) were administered by i.v. bolus injection to male Sprague-Dawley rats. Plasma samples were extracted and subsequently analyzed using a validated LC-MS/MS method. Both non-compartmental and compartmental PK analyses were performed. A stepwise model building approach was applied including nonlinear mixed effect modeling for final model selection and to obtain final model estimates in NONMEM VI. The average areas under the curve (AUC(0-last)) after doses of 1.25, 2.5, and 5mg/kg were 1.03, 3.61, and 12.6 mg *h/l, respectively. The shape of the plasma concentration-time profiles and the observed disproportionate increase in AUC(0 last) with increasing dose suggested nonlinearity in the elimination of visnagin. A two-compartment Michaelis-Menten model provided the best fit with following typical values of the parameter estimates: 2.09 mg/(l*h) (V(max)), 0.08 mg/l (K(M)), 0.175 l (V(C)), 1.0 h-1 (k12), and 1.22 h-1 (k21). Associated inter subject variability estimates (% CV) for V(max), K(M) and V(C) were 21.8, 70.9, and 9.2, respectively. Intra-subject variability (constant CV error model) was estimated to be 7.0%. The results suggest the involvement of a saturable process in the elimination of visnagin, possibly an enzyme or transporter system. PMID- 22085635 TI - Synthesis, stability and pharmacological evaluation of a novel codrug consisting of lamivudine and ursolic acid. AB - A novel codrug (LMX) was obtained from lamivudine (LMV) and ursolic acid (UA) coupled with ethyl chloroacetate through an amide and ester linkage. The structure of LMX was confirmed by 1H NMR, 13C NMR, IR and HRMS. Herein, the in vitro non-enzymatic and enzymatic hydrolysis and in vivo pharmacological activities of LMX were studied. The kinetics of hydrolysis of LMX was studied in aqueous solution of pH 1-10, 80% buffered human plasma and in the presence of lipase from Porcine pancreas (EC 3.1.1.3) at 37 degrees C. It is found that LMX hydrolysis rate was significantly faster in lipase with half-life of 1.4h compared to pH 7.4 phosphate buffer (t(1/2) 11.2h) and buffered human plasma (t(1/2) 5.4h). The decomposition rates in aqueous solution (pH 1-10) showed a U shaped curve. LMX was comparatively stable between pH 3 and 6 (half-life >40 h). Pharmacological studies indicated that LMX had the dual action of anti-hepatitis B virus activity and hepatoprotective effects against acute liver injury. These findings suggest that LMX could be a promising candidate agent for the treatment of hepatitis. PMID- 22085637 TI - Inaccuracies in reporting the accuracy of flap creating devices. PMID- 22085636 TI - Model-based global sensitivity analysis as applied to identification of anti cancer drug targets and biomarkers of drug resistance in the ErbB2/3 network. AB - High levels of variability in cancer-related cellular signalling networks and a lack of parameter identifiability in large-scale network models hamper translation of the results of modelling studies into the process of anti-cancer drug development. Recently global sensitivity analysis (GSA) has been recognised as a useful technique, capable of addressing the uncertainty of the model parameters and generating valid predictions on parametric sensitivities. Here we propose a novel implementation of model-based GSA specially designed to explore how multi-parametric network perturbations affect signal propagation through cancer-related networks. We use area-under-the-curve for time course of changes in phosphorylation of proteins as a characteristic for sensitivity analysis and rank network parameters with regard to their impact on the level of key cancer related outputs, separating strong inhibitory from stimulatory effects. This allows interpretation of the results in terms which can incorporate the effects of potential anti-cancer drugs on targets and the associated biological markers of cancer. To illustrate the method we applied it to an ErbB signalling network model and explored the sensitivity profile of its key model readout, phosphorylated Akt, in the absence and presence of the ErbB2 inhibitor pertuzumab. The method successfully identified the parameters associated with elevation or suppression of Akt phosphorylation in the ErbB2/3 network. From analysis and comparison of the sensitivity profiles of pAkt in the absence and presence of targeted drugs we derived predictions of drug targets, cancer-related biomarkers and generated hypotheses for combinatorial therapy. Several key predictions have been confirmed in experiments using human ovarian carcinoma cell lines. We also compared GSA-derived predictions with the results of local sensitivity analysis and discuss the applicability of both methods. We propose that the developed GSA procedure can serve as a refining tool in combinatorial anti-cancer drug discovery. PMID- 22085638 TI - Biophysical characterization of glycosaminoglycan-IL-7 interactions using SPR. AB - Glycosaminoglycans (GAGs) interact with a number of cytokines and growth factors thereby playing an essential role in the regulation of many physiological processes. These interactions are important for both normal signal transduction and the regulation of the tissue distribution of cytokines/growth factors. In the present study, we employed surface plasmon resonance (SPR) spectroscopy to dissect the binding interactions between GAGs and murine and human forms of interleukin-7 (IL-7). SPR results revealed that heparin binds with higher affinity to human IL-7 than murine IL-7 through a different kinetic mechanism. The optimal oligosaccharide length of heparin for the interactions to human and murine IL-7 involves a sequence larger than a tetrasaccharide. These results further demonstrate that while IL-7 is principally a heparin/heparan sulfate binding protein, it also interacts with dermatan sulfate, chondroitin sulfates C, D, and E, indicating that this cytokine preferentially interacts with GAGs having a higher degree of sulfation. PMID- 22085639 TI - Foot and mouth disease leader protease (Lbpro): Investigation of prime side specificity allows the synthesis of a potent inhibitor. AB - Foot and mouth disease virus expresses its genetic information as a single polyprotein that is translated from the single-stranded RNA genome. Proteinases contained within the polyprotein then generate the mature viral proteins. The leader protease (Lb(pro)) performs the initial cleavage by freeing itself from the growing polypeptide chain; subsequently, Lb(pro) cleaves the two homologues of the host cell protein eukaryotic initiation factor 4G (eIF4G). We showed that Lb(pro) possesses specific binding sites at the non prime side from S(1) down to S(7) [Santos et al. (2009) Biochemistry, 48, 7948-7958]. Here, we demonstrate that Lb(pro) has high prime side specificity at least down to the S'(5) site. Lb(pro) is thus not only one of the smallest papain-like cysteine peptidases but also one of the most specific. It can still however cleave between both K?G and G?R pairs. We further determined the two-step irreversible inhibition (E + I <-> EI-> E - I) kinetic parameters of two known irreversible epoxide-based inhibitors of cysteine proteinases, E64 and CA074 on Lb(pro) that show for the reversible step (E + I <-> EI) K(i) = 3.4 MUM and 11.6 MUM, and for the irreversible step (EI->E-I) k(4) = 0.16 and 0.06 min(-1), respectively. Knowledge of the Lb(pro) specificity led us to extend E64 by addition of the dipeptide R-P. This compound, termed E64-R-P-NH(2), irreversibly inhibited Lb(pro) with a K(i) = 30 nM and k(4) = 0.01 min(-1) and can serve as the basis for design of specific inhibitors of FMDV replication. PMID- 22085640 TI - Selection of RNA aptamers against mouse embryonic stem cells. AB - Embryonic stem cells (ESCs) are capable of unlimited self-renewal and differentiation into multiple cell types. Recent large-scale analyses have identified various cell surface molecules on ESCs. Some of them are considered to be beneficial markers for characterization of cellular phenotypes and/or play an essential role for regulating the differentiation state. Thus, it is desired to efficiently produce affinity reagents specific to these molecules. In this study, to develop such reagents for mouse ESCs (mESCs), we selected RNA aptamers against intact, live mESCs using several selection strategies. The initial selection provided us with several anti-mESC aptamers of distinct sequences, which unexpectedly react with the same molecule on mESCs. Then, to isolate aptamers against different surface markers on mESCs, one of the selected aptamers was used as a competitor in the subsequent selections. In addition, one of the selections further employed negative selection against differentiated mouse cells. Consequently, we successfully isolated three classes of anti-mESC aptamers that do not compete with one another. The isolated aptamers were shown to distinguish mESCs from differentiated mouse cell lines and trace the differentiation process of mESCs. These aptamers could prove useful for developing molecular probes and manipulation tools for mESCs. PMID- 22085641 TI - Aberrant T-lymphocyte development and function in mice overexpressing human soluble amyloid precursor protein-alpha: implications for autism. AB - Abnormalities in T-lymphocyte populations and function are observed in autism. Soluble amyloid precursor protein alpha (sAPP-alpha) is elevated in some patients with autism and is known to be produced by immune cells. In light of the well established role of sAPP-alpha in proliferation, growth, and survival of neurons, we hypothesized an analogous role in the immune system. Thus, we explored whether sAPP-alpha could modulate immune development and function, especially aspects of the pinnacle cell of the adaptive arm of the immune system: the T cell. To do this, we generated mice overexpressing human sAPP-alpha and characterized elements of T-cell development, signal transduction, cytokine production, and innate/adaptive immune functions. Here, we report that transgenic sAPP-alpha overexpressing (TgsAPP-alpha) mice displayed increased proportions of CD8(+) T cells, while effector memory T cells were decreased in the thymus. Overall apoptotic signal transduction was decreased in the thymus, an effect that correlated with dramatic elevations in Notch1 activation; while active-caspase 3/total-caspase-3 and Bax/Bcl-2 ratios were decreased. Greater levels of IFN gamma, IL-2, and IL-4 were observed after ex vivo challenge of TgsAPP-alpha mouse splenocytes with T-cell mitogen. Finally, after immunization, splenocytes from TgsAPP-alpha mice displayed decreased levels IFN-gamma, IL-2, and IL-4, as well as suppressed ZAP70 activation, after recall antigen stimulation. Given elevated levels of circulating sAPP-alpha in some patients with autism, sAPP-alpha could potentially drive aspects of immune dysfunction observed in these patients, including dysregulated T-cell apoptosis, aberrant PI3K/AKT signaling, cytokine alterations, and impaired T-cell recall stimulation. PMID- 22085642 TI - Oxidation of HRas cysteine thiols by metabolic stress prevents palmitoylation in vivo and contributes to endothelial cell apoptosis. AB - Here we demonstrate a new paradigm in redox signaling, whereby oxidants resulting from metabolic stress directly alter protein palmitoylation by oxidizing reactive cysteine thiolates. In mice fed a high-fat, high-sucrose diet and in cultured endothelial cells (ECs) treated with high palmitate and high glucose (HPHG), there was decreased HRas palmitoylation on Cys181/184 (61+/-24% decrease for cardiac tissue and 38+/-7.0% in ECs). This was due to oxidation of Cys181/184, detected using matrix-assisted laser desorption/ionization time of flight (MALDI TOF)-TOF. Decrease in HRas palmitoylation affected its compartmentalization and Ras binding domain binding activity, with a shift from plasma membrane tethering to Golgi localization. Loss of plasma membrane-bound HRas decreased growth factor stimulated ERK phosphorylation (84+/-8.6% decrease) and increased apoptotic signaling (24+/-6.5-fold increase) after HPHG treatment that was prevented by overexpressing wild-type but not C181/184S HRas. The essential role of HRas in metabolic stress was made evident by the similar effects of expressing an inactive dominant negative N17-HRas or a MEK inhibitor. Furthermore, the relevance of thiol oxidation was demonstrated by overexpressing manganese superoxide dismutase, which improved HRas palmitoylation and ERK phosphorylation, while lessening apoptosis in HPHG treated ECs. PMID- 22085643 TI - The cysteines of the extracellular loop are crucial for trafficking of human organic cation transporter 2 to the plasma membrane and are involved in oligomerization. AB - Human organic cation transporter 2 (hOCT2) is involved in transport of many endogenous and exogenous organic cations, mainly in kidney and brain cells. Because the quaternary structure of transmembrane proteins plays an essential role for their cellular trafficking and function, we investigated whether hOCT2 forms oligomeric complexes, and if so, which part of the transporter is involved in the oligomerization. A yeast 2-hybrid mating-based split-ubiquitin system (mbSUS), fluorescence resonance energy transfer, Western blot analysis, cross linking experiments, immunofluorescence, and uptake measurements of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium were applied to human embryonic kidney 293 (HEK293) cells transfected with hOCT2 and partly also to freshly isolated human proximal tubules. The role of cysteines for oligomerization and trafficking of the transporter to the plasma membranes was investigated in cysteine mutants of hOCT2. hOCT2 formed oligomers both in the HEK293 expression system and in native human kidneys. The cysteines of the large extracellular loop are important to enable correct folding, oligomeric assembly, and plasma membrane insertion of hOCT2. Mutation of the first and the last cysteines of the loop at positions 51 and 143 abolished oligomer formation. Thus, the cysteines of the extracellular loop are important for correct trafficking of the transporter to the plasma membrane and for its oligomerization. PMID- 22085644 TI - Loss of desmin triggers mechanosensitivity and up-regulation of Ankrd1 expression through Akt-NF-kappaB signaling pathway in smooth muscle cells. AB - Muscle cells, including human airway smooth muscle cells (HASMCs) express ankyrin repeat protein 1 (Ankrd1), a member of ankyrin repeat protein family. Ankrd1 efficiently interacts with the type III intermediate filament desmin. Our earlier study showed that desmin is an intracellular load-bearing protein that influences airway compliance, lung recoil, and airway contractile responsiveness. These results suggest that Ankrd1 and desmin may play important roles on ASMC homeostasis. Here we show that small interfering (si)RNA-mediated knockdown of the desmin gene in HASMCs, recombinant HASMCs (reHASMCs), up-regulates Ankrd1 expression. Moreover, loss of desmin in HASMCs increases the phosphorylation of Akt, inhibitor of kappaB kinase (IKK)-alpha, and inhibitor of kappaB (IkappaB) alpha proteins, leading to NF-kappaB activation. Treatment of reHASMCs with Akt, IKKalpha, IkappaBalpha, or NF-kappaB inhibitor inhibits the loss of desmin induced Ankrd1 up-regulation, suggesting Akt/NF-kappaB-mediated Ankrd1 regulation. Transfection of reHASMCs with siRNA specific for p50 or p65 corroborates the NF-kappaB-mediated Ankrd1 regulation. Luciferase reporter assays show that NF-kappaB directly binds on Ankrd1 promoter and up-regulates Ankrd1 levels. Overall, our data provide a new link between desmin and Ankrd1 regulation, which may be important for ASMC homeostasis. PMID- 22085645 TI - Interactions between different generation HIV-1 fusion inhibitors and the putative mechanism underlying the synergistic anti-HIV-1 effect resulting from their combination. AB - We previously reported that the combinatorial use of T20 and T1144, the first and next generations of HIV fusion inhibitors, containing different functional domains resulted in synergistic anti-HIV-1 effect, but this effect diminished when T20 and T1144 were covalently linked together. To elucidate the mechanism underlying this synergistic anti-HIV-1 effect, we studied the interactions between T20 and T1144 either in a mixture state or in a covalently linked state. T20 alone in solution was largely featureless, while T1144 alone was in alpha helical trimeric conformation. When mixed in solution, T20 and T1144 showed a loose and transient interaction, with a moderate 10% alpha-helical content increase, but this interaction was greatly enhanced in the linked state, and T20 and T1144 showed ~100% alpha-helical content. These results suggested that the loose and transient interaction between T20 and T1144 may destabilize the T1144 trimer, which makes its otherwise shielded binding sites more accessible to N terminal heptad repeat (NHR) and increases its associating rate, thus increasing its anti-HIV-1 potency against the temporarily exposed target in NHR and causing the synergistic anti-HIV-1 effect. However, the strong interaction between T20 and T1144 in the covalently linked state may shield their NHR-binding sites, resulting in reduction of the synergistic effect. PMID- 22085646 TI - Structural features of the KPI domain control APP dimerization, trafficking, and processing. AB - The two major isoforms of human APP, APP695 and APP751, differ by the presence of a Kunitz-type protease inhibitor (KPI) domain in the extracellular region. APP processing and function is thought to be regulated by homodimerization. We used bimolecular fluorescence complementation (BiFC) to study dimerization of different APP isoforms and mutants. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain did not affect fluorescence complementation, but native folding of KPI is critical for APP751 homodimerization. APP751 and APP695 dimers were mostly localized at steady state in the Golgi region, suggesting that most of the APP751 and 695 dimers are in the secretory pathway. Mutation of the KPI led to the retention of the APP homodimers in the endoplasmic reticulum. We finally showed that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695. These findings provide new insight on the particular role of KPI domain in APP dimerization. The correlation observed between dimerization, subcellular localization, and processing suggests that dimerization acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing. PMID- 22085647 TI - Localisation to lipid rafts correlates with increased function of the Gal/GalNAc lectin in the human protozoan parasite, Entamoeba histolytica. AB - Entamoeba histolytica is the causative agent of dysentery and liver abscess and is prevalent in developing countries. Adhesion to the host is critical to infection and is mediated by amoebic surface receptors. One such receptor, the Gal/GalNAc lectin, binds to galactose or N-acetylgalactosamine residues on host components and consists of heavy (Hgl), light (Lgl) and intermediate (Igl) subunits. The mechanism by which the lectin assembles into a functional complex is not known. The parasite also relies on cholesterol-rich domains (lipid rafts) for adhesion. Therefore, it is conceivable that rafts regulate the assembly or function of the lectin. To test this, amoebae were loaded with cholesterol and lipid rafts were purified and characterised. Western blotting showed that cholesterol loading resulted in co-compartmentalisation of all three subunits in rafts. This co-compartmentalisation was accompanied by an increase in the ability of the amoebae to bind to host cells in a galactose-specific manner, suggesting that there is a correlation between location and function of the Gal/GalNAc lectin. Cholesterol loading did not increase the surface levels of the lectin subunits. Therefore, the cholesterol-induced increase in adhesion was not the result of externalisation of an internal pool of subunits. A mutant cell line that modestly responded to cholesterol with a slight increase in adhesion exhibited only a slight enrichment of Hgl and Lgl in rafts. This supports the connection between location and function of the Gal/GalNAc lectin. Actin can also influence the interaction of proteins with rafts. Therefore, the sub-membrane distribution of the lectin subunits was also assessed after treatment with an actin depolymerising agent, cytochalasin D. Cytochalasin D-treatment had no effect on the submembrane distribution of the subunits, suggesting that actin does not prevent the association of lectin subunits with rafts in this system. Together, these data provide insight into the molecular mechanisms regulating the location and function of this adhesin. PMID- 22085648 TI - Carboxylesterases 1 and 2 hydrolyze phospho-nonsteroidal anti-inflammatory drugs: relevance to their pharmacological activity. AB - Phospho-nonsteroidal anti-inflammatory drugs (phospho-NSAIDs) are novel NSAID derivatives with improved anticancer activity and reduced side effects in preclinical models. Here, we studied the metabolism of phospho-NSAIDs by carboxylesterases and assessed the impact of carboxylesterases on the anticancer activity of phospho-NSAIDs in vitro and in vivo. The expression of human liver carboxylesterase (CES1) and intestinal carboxylesterase (CES2) in human embryonic kidney 293 cells resulted in the rapid intracellular hydrolysis of phospho NSAIDs. Kinetic analysis revealed that CES1 is more active in the hydrolysis of phospho-sulindac, phospho-ibuprofen, phospho-naproxen, phospho-indomethacin, and phospho-tyrosol-indomethacin that possessed a bulky acyl moiety, whereas the phospho-aspirins are preferentially hydrolyzed by CES2. Carboxylesterase expression leads to a significant attenuation of the in vitro cytotoxicity of phospho-NSAIDs, suggesting that the integrity of the drug is critical for anticancer activity. Benzil and bis-p-nitrophenyl phosphate (BNPP), two carboxylesterase inhibitors, abrogated the effect of carboxylesterases and resensitized carboxylesterase-expressing cells to the potent cytotoxic effects of phospho-NSAIDs. In mice, coadministration of phospho-sulindac and BNPP partially protected the former from esterase-mediated hydrolysis, and this combination more effectively inhibited the growth of AGS human gastric xenografts in nude mice (57%) compared with phospho-sulindac alone (28%) (p = 0.037). Our results show that carboxylesterase mediates that metabolic inactivation of phospho-NSAIDs, and the inhibition of carboxylesterases improves the efficacy of phospho-NSAIDs in vitro and in vivo. PMID- 22085649 TI - 3-Substituted pyrazole analogs of the cannabinoid type 1 (CB1) receptor antagonist rimonabant: cannabinoid agonist-like effects in mice via non-CB1, non CB2 mechanism. AB - The prototypic cannabinoid type 1 (CB1) receptor antagonist/inverse agonist, rimonabant, is comprised of a pyrazole core surrounded by a carboxyamide with terminal piperidine group (3-substituent), a 2,4-dichlorophenyl group (1 substituent), a 4-chlorophenyl group (5-substituent), and a methyl group (4 substituent). Previous structure-activity relationship (SAR) analysis has suggested that the 3-position may be involved in receptor recognition and agonist activity. The goal of the present study was to develop CB1-selective compounds and explore further the SAR of 3-substitution on the rimonabant template. 3 Substituted analogs with benzyl and alkyl amino, dihydrooxazole, and oxazole moieties were synthesized and evaluated in vitro and in vivo. Several notable patterns emerged. First, most of the analogs exhibited CB1 selectivity, with many lacking affinity for the CB2 receptor. Affinity tended to be better when [3H]5-(4 chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3 carboxamide (SR141716), rather than [3H](-)-cis-3-[2-hydroxy-4(1,1-dimethyl heptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexanol (CP55,940), was used as the binding radioligand. Second, many of the analogs produced an agonist-like profile of effects in mice (i.e., suppression of activity, antinociception, hypothermia, and immobility); however, their potencies were not well correlated with their CB1 binding affinities. Further assessment of selected analogs showed that none were effective antagonists of the effects of Delta9-tetrahydrocannabinol in mice, their agonist-like effects were not blocked by rimonabant, they were active in vivo in CB1-/- mice, and they failed to stimulate guanosine-5'-O-(3-[35S]thio) triphosphate binding. Several analogs were inverse agonists in the latter assay. Together, these results suggest that this series of 3-substituted pyrazole analogs represent a novel class of CB1-selective cannabinoids that produce agonist-like effects in mice through a non-CB1, non-CB2 mechanism. PMID- 22085650 TI - Effects of feeding polydextrose on faecal characteristics, microbiota and fermentative end products in healthy adult dogs. AB - Polydextrose is a potential prebiotic, but has not been well tested in dogs. Thus, the objective of the present study was to determine the effects of polydextrose on faecal characteristics, microbial populations and fermentative end products in healthy adult dogs. A total of eight adult hound dogs (3.5 (sem 0.5) years; 20 (sem 0.5) kg) were randomly allotted to one of four test diets containing the following concentrations of polydextrose: (1) 0 % (control); (2) 0.5 %; (3) 1.0 %; or (4) 1.5 %. A Latin square design was used, with each treatment period lasting 14 d (days 0-10 adaptation; days 11-14 fresh and total faecal collection). All dogs were fed to maintain body weight. Data were evaluated for linear and quadratic effects using SAS software. Although apparent total tract DM digestibility was unaffected, total tract crude protein digestibility tended to decrease (P < 0.10) linearly with increasing dietary polydextrose concentrations. Fresh faecal DM percentage tended to decrease (P < 0.10) linearly, while faecal scores increased (P < 0.05; looser stools) with increasing dietary concentrations of polydextrose. Faecal acetate, propionate and total SCFA concentrations increased (P < 0.05) linearly with increased dietary polydextrose. Faecal pH decreased (P < 0.05) linearly with increasing polydextrose. Faecal indole tended to decrease (P < 0.10) linearly with increasing polydextrose, but other faecal protein catabolites were not changed. Faecal Clostridium perfringens linearly decreased (P < 0.05) with increasing dietary polydextrose concentrations, but Escherichia coli, Lactobacillus spp. and Bifidobacterium spp. were not affected. Based on the present results, polydextrose appears to act as a highly fermentable fibre, but requires further research to test its potential as a prebiotic in dogs. PMID- 22085651 TI - Interference of kallikrein 1b26 (klk1b26) translation by microRNA specifically expressed in female mouse submandibular glands: an additional mechanism for sexual dimorphism of klk1b26 protein in the glands. AB - BACKGROUND: Mouse kallikrein 1b26 (klk1b26) protein is more abundant in male submandibular glands (SMGs) than in female ones. This sexual dimorphism has been thought to be due to increased mRNA synthesis stimulated by androgen. However, the klk1b26 protein level in female SMG is far less than that expected from the mRNA level, suggesting an additional mechanism for down-regulation of klk1b26 expression in female SMGs. METHODS: We examined the effects of small non-coding RNAs in mouse SMGs on in vitro translation of klk1b26 using a reticulocyte lysate system and reverse transcription (RT)-PCR for klk1b26 mRNA. Statistical analyses were performed with a computer package (Microsoft Excel). RESULTS: The microRNA (miRNA) preparation from female SMGs, but not male SMGs, interfered with the in vitro translation of the klk1b26 protein and inhibited the RT-PCR for klk1b26 mRNA with forward primers targeting its 5'-terminal region (between the 15th and 40th nucleotide from the 5'-terminal). The miRNA preparation from castrated mouse SMGs showed the inhibitory effect on the klk1b26 translation, but that from a 5alpha-dihydrotestosterone-treated female mouse SMGs did not. Synthetic miRNAs (miR-325 and miR-1497a), which have partial complementarity with klk1b26 mRNA at its 5'-terminal region (15th to 40th nucleotide position from the 5'-terminal), also interfered with the in vitro klk1b26 translation. When the female miRNA preparation was incubated with a 30-nucleotide-long single-strand oligoDNA (named [15th-44th]ssDNA, whose sequence corresponded to the 15th to 44th position from the 5'-terminal of klk1b26 mRNA) prior to the addition into the in vitro translation system, the inhibitory effect of the miRNA preparation on klk1b26 translation disappeared, while [15th-44th]ssDNA itself had no effect on the translation. Preincubation of the miRNA preparation with another single-strand DNA ([169th-198th]ssDNA, whose sequence corresponded with 169th to 198th position of klk1b26 mRNA) did not show the inhibitory effect. CONCLUSIONS: The small non coding RNA, most probably miRNA, specifically expressed in female mouse SMGs interfered with klk1b26 protein synthesis in the in vitro translation system. Therefore sexual dimorphism observed in klk1b26 expression in mouse SMGs is due at least in part to the female-specific small non-coding RNA in SMGs. PMID- 22085652 TI - Genes, animal models and the current understanding of psychiatric disease. PMID- 22085653 TI - Cellular uptake mechanism and knockdown activity of siRNA-loaded biodegradable DEAPA-PVA-g-PLGA nanoparticles. AB - Efficient downregulation of gene expression depends on the uptake, intracellular distribution and efficient release of siRNA from their carrier. Therefore, the cellular uptake behavior and mechanism and intracellular localization of siRNA loaded biodegradable nanoparticles were investigated. A biodegradable polymer, composed of poly(vinyl alcohol) (PVA) modified with diamine moieties and grafted with PLGA, abbreviated as DEAPA-PVA-g-PLGA, was used for the preparation of siRNA loaded nanoparticles by solvent displacement. Particle sizes and morphology were determined by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The dependence of particle uptake into H1299-EGFP cells (lung cancer cells expressing green fluorescent protein) on both incubation time and temperature was studied by flow cytometry. Inhibition experiments focusing on clathrin- or caveolae-mediated uptake or uptake by macropinocytosis were performed. The intracellular localization was investigated by confocal laser scanning microscopy. The GFP knockdown efficiency was determined in vitro to establish the potential of the nanoparticles for the downregulation of gene expression. Nanoparticles with diameters of 120-180nm were successfully generated. In contrast to the uptake of standard PEI-polyplexes, which increased continuously over a period of 4h, nanoparticle uptake was complete within 2h. A decrease in particle uptake at 4 degrees C (in comparison with 37 degrees C) suggests an active uptake process. Inhibition experiments revealed the predominance of clathrin-mediated uptake for siRNA-loaded nanoparticles. The siRNA-loaded nanoparticles could be clearly located within cells, mainly in intracellular vesicles. Particle uptake could be increased by the addition of lung surfactant to the formulation. Bioactivity in terms of successful GFP knockdown in vitro was demonstrated and could be further optimized by the use of surfactant-modified particles. In conclusion, a high and rapid cellular uptake was shown for siRNA loaded nanoparticles. Cell internalization is based on an energy-dependent and predominantly clathrin-mediated process. Particle localization in endosomes and lysosomes was demonstrated. Evidence for the efficient delivery of bioactive siRNA and specific GFP knockdown provides a solid basis for the application of DEAPA-PVA-g-PLGA-based particles for gene silencing in vivo. PMID- 22085654 TI - beta-Casein nanoparticle-based oral drug delivery system for potential treatment of gastric carcinoma: stability, target-activated release and cytotoxicity. AB - We studied a potential drug delivery system comprising the hydrophobic anticancer drug paclitaxel entrapped within beta-casein (beta-CN) nanoparticles and its cytotoxicity to human gastric carcinoma cells. Paclitaxel was entrapped by stirring its dimethyl sulfoxide (DMSO) solution into PBS containing beta-CN. Cryo TEM analysis revealed drug nanocrystals, the growth of which was blocked by beta CN. Entrapment efficiency was nearly 100%, and the nanovehicles formed were colloidally stable. Following encapsulation and simulated digestion with pepsin (2 hours at pH=2, 37 degrees C), paclitaxel retained its cytotoxic activity to human N-87 gastric cancer cells; the IC(50) value (32.5 +/- 6.2 nM) was similar to that of non-encapsulated paclitaxel (25.4 +/- 2.6 nM). Without prior simulated gastric digestion, beta-CN-paclitaxel nanoparticles were non-cytotoxic, suggesting the lack of untoward toxicity to bucal and esophageal epithelia. We conclude that beta-CN shows promise to be useful for target-activated oral delivery of hydrophobic chemotherapeutics in the treatment of gastric carcinoma, one of the leading causes of cancer mortality worldwide. PMID- 22085656 TI - The anthocyanin cyanidin-3-O-beta-glucoside, a flavonoid, increases hepatic glutathione synthesis and protects hepatocytes against reactive oxygen species during hyperglycemia: Involvement of a cAMP-PKA-dependent signaling pathway. AB - Enhanced oxidative stress due to high glucose contributes to pathological changes in diabetes-related liver complications. Reducing oxidative stress may alleviate these pathogenic processes. Anthocyanin, a natural antioxidant, has been reported to reduce intracellular reactive oxygen species (ROS) levels but the mechanism of this reduction is not fully understood. The glutathione (GSH) antioxidant system is critical for counteracting oxidative stress-induced intracellular injury. In this study, we evaluated the mechanism of the anthocyanin-mediated regulation of GSH synthesis and reduction in intracellular ROS levels. We observed that treatment of human HepG2 cells with the anthocyanin C3G significantly reduced ROS levels induced by high glucose. C3G incubation increased glutamate-cysteine ligase expression, which in turn mediated the reduction in ROS levels. However, the upregulation of glutamate-cysteine ligase catalytic subunit (Gclc) expression by C3G occurred independent of the Nrf1/2 transcription factors. Notably, the cAMP-response element binding protein (CREB) was identified as the target transcription factor involved in the C3G-mediated upregulation of Gclc expression. C3G increased phosphorylation of CREB through protein kinase A (PKA) activation, which induced a CREB-mediated upregulation of Gclc transcription. In vivo, treatment with C3G increased the GSH synthesis in the liver of diabetic db/db mice through PKA-CREB-dependent induction of Gclc expression. Finally, oxidative stress determined by lipid peroxidation, neutrophil infiltration, and hepatic steatosis was attenuated in C3G-treated db/db mice. Our results demonstrate that the anthocyanin C3G has an effect of activating GSH synthesis through a novel antioxidant defense mechanism against excessive ROS production, contributing to the prevention of hyperglycemia-induced hepatic oxidative damage. PMID- 22085655 TI - The role of sirtuins in modulating redox stressors. AB - For much of the time since their discovery, the sirtuin family of deacetylase enzymes has been associated with extension of life span. This longevity-promoting capacity in numerous model systems has enabled the sirtuins to gain "celebrity status" in the field of aging research. However, the mechanisms underpinning these changes remain incompletely defined. A general phenotype long associated with aging is the dysregulation of biological systems, which partly occurs via the accumulation of damage over time. One of the major sources of this damage is oxidative stress, which can harm both biological structures and the mechanisms with which they are repaired. It is now becoming clear that the beneficial life span effects of sirtuins, along with many of their other functions, are closely linked to their ability to regulate systems that control the redox environment. Here we investigate the links between sirtuins and their oxidative/redox environment and review the control mechanisms that are regulated by the activity of sirtuin deacetylase proteins. PMID- 22085657 TI - Gestatational trophoblastic disease: multimodality imaging assessment with special emphasis on spectrum of abnormalities and value of imaging in staging and management of disease. AB - Gestational trophoblastic disease is a spectrum of disorders of varying malignant potential arising from trophoblastic cells and encompassing hydatidiform moles and persistent trophoblastic neoplasia. Ultrasound is the initial imaging investigation of choice when gestational trophoblastic disease is suspected. Complete hydatiform mole, the most common form of molar pregnancy, usually has a characteristic "cluster of grapes" appearance, especially on second-trimester ultrasounds. Persistent trophobastic neoplasia usually appears as a focal, hypervascular myometrial mass on pelvic ultrasound. Pelvic magnetic resonance imaging is often used as a problem-solving tool in equivocal or complicated cases of gestational trophoblastic disease to assess the degree of invasion into the myometrium and surrounding tissues. Chest x-ray, brain magnetic resonance imaging, and body computed tomography scans are primarily used for the evaluation of metastatic disease, which usually occurs in the context of choriocarcinomas. Choriocarcinoma metastases are usually hypervascular and have a tendency to bleed, features that are reflected in their imaging appearance. PMID- 22085658 TI - Neuroimaging of migrational disorders in pediatric epilepsy. AB - Seizures in children are common and represent a final pathway for a variety of brain insults. Although most children with seizures do not require imaging, when indicated, imaging plays an important role in the clinical workup. Imaging in the pediatric seizure population is reserved for a particular subset of patients depending on factors, such as age of onset, symptomatology, physical examination findings, and specific electroencephalography changes to name a few. The etiologies of seizures are extensive and include disorders of cortical migration and organization. Cortical migration and organization disorders are multifactorial and complex and a major cause of seizure disorders. Although magnetic resonance imaging is the most common imaging modality used to identify the seizure focus, positron emission tomographic and/or diffusion tensor imaging are beginning to provide complementary information about the involved areas. Early and accurate detection is key to better treatment and overall improved patient prognosis. PMID- 22085659 TI - Imaging of duodenal diverticula and their complications. AB - Duodenal diverticula are common and are often incidentally found during routine imaging. Complications can occur but few require surgical intervention. We present a review of duodenal diverticula and their complications. PMID- 22085660 TI - Spectrum of synovial pathologies: a pictorial assay. AB - The synovium, a specialized vascular tissue, lines the diarthrodial joints, bursae, and tendon sheaths of the body. It helps in nourishment of articular structures. The synovium is affected by a variety of disorders that can be either localized or systemic. Although normal synovium is barely perceptible on magnetic resonance imaging, it provides an excellent imaging modality for the evaluation of pathologic processes involving the synovium. The pathologic processes affecting the synovium include 1 of the following etiologies: inflammatory, infectious, degenerative, traumatic, or neoplastic and tumor-like conditions. In this article, we discuss the magnetic resonance imaging technique and the sequences used in the evaluation of synovial pathologies and review the characteristic imaging findings of specific conditions thus narrowing the differential diagnoses. PMID- 22085661 TI - Twenty years after: do animal trials inform clinical resuscitation research? PMID- 22085662 TI - Do long-acting beta2 agonists impair the effect of short-acting beta2 agonists in some patients? PMID- 22085664 TI - Antibiotics for acute otitis media in young children. PMID- 22085665 TI - Anaphylaxis: recognition and management. AB - Anaphylaxis is a severe, life-threatening, systemic allergic reaction that is almost always unanticipated and may lead to death by airway obstruction or vascular collapse. Anaphylaxis occurs as the result of an allergen response, usually immunoglobulin E-mediated, which leads to mast cell and basophil activation and a combination of dermatologic, respiratory, cardiovascular, gastrointestinal, and neurologic symptoms. Dermatologic and respiratory symptoms are most common, occurring in 90 and 70 percent of episodes, respectively. The three most common triggers are food, insect stings, and medications. The diagnosis of anaphylaxis is typically made when symptoms occur within one hour of exposure to a specific antigen. Confirmatory testing using serum histamine and tryptase levels is difficult, because blood samples must be drawn with strict time considerations. Allergen skin testing and in vitro assay for serum immunoglobulin E of specific allergens do not reliably predict who will develop anaphylaxis. Administration of intramuscular epinephrine at the onset of anaphylaxis, before respiratory failure or cardiovascular compromise, is essential. Histamine H(1) receptor antagonists and corticosteroids may be useful adjuncts. All patients at risk of recurrent anaphylaxis should be educated about the appropriate use of prescription epinephrine autoinjectors. PMID- 22085666 TI - Evaluation of chronic diarrhea. AB - Chronic diarrhea, defined as a decrease in stool consistency for more than four weeks, is a common but challenging clinical scenario. It can be divided into three basic categories: watery, fatty (malabsorption), and inflammatory. Watery diarrhea may be subdivided into osmotic, secretory, and functional types. Watery diarrhea includes irritable bowel syndrome, which is the most common cause of functional diarrhea. Another example of watery diarrhea is microscopic colitis, which is a secretory diarrhea affecting older persons. Laxative-induced diarrhea is often osmotic. Malabsorptive diarrhea is characterized by excess gas, steatorrhea, or weight loss; giardiasis is a classic infectious example. Celiac disease (gluten-sensitive enteropathy) is also malabsorptive, and typically results in weight loss and iron deficiency anemia. Inflammatory diarrhea, such as ulcerative colitis or Crohn disease, is characterized by blood and pus in the stool and an elevated fecal calprotectin level. Invasive bacteria and parasites also produce inflammation. Infections caused by Clostridium difficile subsequent to antibiotic use have become increasingly common and virulent. Not all chronic diarrhea is strictly watery, malabsorptive, or inflammatory, because some categories overlap. Still, the most practical diagnostic approach is to attempt to categorize the diarrhea by type before testing and treating. This narrows the list of diagnostic possibilities and reduces unnecessary testing. Empiric therapy is justified when a specific diagnosis is strongly suspected and follow-up is available. PMID- 22085667 TI - Chronic diarrhea. PMID- 22085668 TI - Chronic kidney disease: detection and evaluation. AB - Chronic kidney disease affects an estimated 27 million adults in the United States, and is associated with significantly increased risk of cardiovascular disease and stroke. Patients should be assessed annually to determine whether they are at increased risk of developing chronic kidney disease based on clinical and sociodemographic factors. Diabetes mellitus, hypertension, and older age are the primary risk factors that warrant screening. Other risk factors include cardiovascular disease, family history of chronic kidney disease, and ethnic and racial minority status. Serum creatinine levels can be used to estimate the glomerular filtration rate, and spot urine testing can detect proteinuria. After the diagnosis of chronic kidney disease is made, staging based on estimated glomerular filtration rate determines prognosis, evaluation, and management. Further evaluation should focus on the specific type of kidney disease and on identifying complications related to the disease stage. Patients should be assessed for risk factors leading to the further loss of kidney function and cardiovascular disease. Patients with estimated glomerular filtration rates less than 30 mL per minute per 1.73 m(2), significant proteinuria, or rapid loss of kidney function should be referred to a nephrologist for further evaluation and management. PMID- 22085669 TI - Clinical vignettes in geriatric depression. AB - The diagnosis of depression in older patients is often complicated by comorbid conditions, such as cerebrovascular disease or dementia. Tools specific for this age group, such as the Geriatric Depression Scale or the Cornell Scale for Depression in Dementia, may assist in making the diagnosis. Treatment decisions should consider risks associated with medications, such as serotonin syndrome, hyponatremia, falls, fractures, and gastrointestinal bleeding. Older white men with depression are at high risk of suicide. Depression is common after stroke or myocardial infarction, and response to antidepressant treatment has been linked to vascular outcomes. Depression care management is an important adjunct to the use of antidepressant medications. Structured psychotherapy and exercise programs are useful treatments for select patients. PMID- 22085670 TI - Caring for older family members with depression. PMID- 22085671 TI - Patient with plaques on lower extremities and systemic symptoms. PMID- 22085672 TI - Colonic diverticular disease. PMID- 22085674 TI - Transcriptional regulation of the PTTH receptor in prothoracic glands of the silkworm, Bombyx mori. AB - The present study investigated transcriptional regulation of the prothoracicotropic hormone (PTTH) receptor (Torso) gene in prothoracic glands (PGs) of the silkworm, Bombyx mori. The results showed that PTTH treatment in vitro time-dependently affected Torso mRNA levels, with an inhibitory effect being detected after 1- and 2-h periods of incubation. When methoprene, a juvenile hormone analogue (JHA), was applied to newly ecdysed last instar larvae, a decline in Torso mRNA levels during the early last larval instar was delayed compared to those treated with acetone. Injection of 20-hydroxyecdysone appeared to have a stimulatory effect on Torso mRNA levels. Torso mRNA levels were also shown to be nutrition-sensitive. From these results, it was suggested that Torso mRNA levels of the PGs appear to be hormonally regulated and nutrition-sensitive, and the endogenous precisely coordinated regulation of Torso mRNA levels may play a role in regulating ecdysteroidogenesis by PGs during development. PMID- 22085675 TI - Cellulolytic environment in the midgut of the wood-feeding higher termite Nasutitermes takasagoensis. AB - Unlike lower termites, xylophagous higher termites thrive on wood without the aid of symbiotic protists. In the higher termite Nasutitermes takasagoensis, both endogenous endo-beta-1,4-glucanase and beta-glucosidase genes are expressed in the midgut, which is believed to be the main site of cellulose digestion. To further explore the detailed cellulolytic system in the midgut of N. takasagoensis, we performed immunohistochemistry and digital light microscopy to determine distributions of cellulolytic enzymes in the salivary glands and the midgut as well as the total cellulolytic activity in the midgut. Although cellulolytic enzymes were uniformly produced in the midgut epithelium, the concentration of endo-beta-1,4-glucanase activity and luminal volume in the midgut were comparable to those of the wood-feeding lower termite Coptotermes formosanus, which digests cellulose with the aid of hindgut protists. However, the size of ingested wood particles was considerably larger in N. takasagoensis than that in C. formosanus. Nevertheless, it is possible that the cellulolytic system in the midgut of N. takasagoensis hydrolyzes highly crystalline cellulose to a certain extent. The glucose produced did not accumulate in the midgut lumen. Therefore, the present study suggests that the midgut of the higher termite provides the necessary conditions for cellulolysis. PMID- 22085676 TI - Effect of bis(maltolato)oxovanadium (IV) (BMOV) on selenium nutritional status in diabetic streptozotocin rats. AB - The role of V as a micronutrient, and its hypoglycaemic and toxicological activity, have yet to be completely established. The present study focuses on changes in the bioavailability and tissue distribution of Se in diabetic streptozotocin rats following treatment with V. The following four study groups were examined: control; diabetic (DM); diabetic treated with 1 mg V/d (DMV); diabetic treated with 3 mg V/d (DMVH). V was supplied in the drinking water as bis(maltolato)oxovanadium (IV). The experiment had a duration of 5 weeks. Se was measured in food, faeces, urine, serum, muscle, kidney, liver and spleen. Glucose and insulin serum were studied, together with glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione transferase (GST) activity and malondialdehyde (MDA) levels in the liver. In the DM group, we recorded higher levels of food intake, Se absorbed, Se retained, Se content in the kidney, liver and spleen, GSH-Px and GST activity, in comparison with the control rats. In the DMV group, there was a significant decrease in food intake, Se absorbed, Se retained and Se content in the liver and spleen, and in GSH-Px and GST activity, while fasting glycaemia and MDA remained unchanged, in comparison with the DM group. In the DMVH group, there was a significant decrease in food intake, glycaemia, Se absorbed, Se retained, Se content in the kidney, liver and spleen, and in GSH-Px and GST activity, and increased MDA, in comparison with the DM and DMV groups. We conclude that under the experimental conditions described, the treatment with 3 mg V/d caused a tissue depletion of Se that compromised Se nutritional status and antioxidant defences in the tissues. PMID- 22085677 TI - Complex formation and kinetics of filament assembly exhibited by the simple epithelial keratins K8 and K18. AB - We have generated human recombinant keratins K8 and K18 and describe conditions to quantitatively follow their assembly into filaments. When renatured individually from 8M urea into a low ionic strength/high pH-buffer, K8 was present in a dimeric to tetrameric form as revealed by analytical ultracentrifugation. In contrast, K18 sedimented as a monomer. When mixed in 8 M urea and renatured together, K8 and K18 exhibited s-value profiles compatible with homogeneous tetrameric complexes. This finding was confirmed by sedimentation equilibrium centrifugation. Subsequently, these tetrameric starter units were subjected to assembly experiments at various protein concentrations. At low values such as 0.0025 g/l, unit-length filaments were abundantly present after 2s of assembly. During the following 5 min, filaments grew rapidly and by measuring the length of individual filaments we were able to generate time dependent length profiles. These data revealed that keratins K8/K18 assemble several times faster than vimentin and desmin. In addition, we determined the persistence length l(p) of K8/K18 filaments to be in the range of 300 nm. Addition of 1 mM MgCl(2) increases l(p) to 480 nm indicating that magnesium ions affect the interaction of keratin subunits within the filament during assembly to some extent. PMID- 22085678 TI - Intentional forgetting might be more effortful than remembering: an ERP study of item-method directed forgetting. AB - This study recorded ERPs while participants engaged in a procedure that combined semantic priming and item-method directed forgetting, aiming to investigate the issues of whether intentional forgetting demands cognitive efforts and modulates the semantic processing of to-be-remembered (TBR) and to-be-forgotten (TBF) items. Participants made lexical decisions to semantically related or unrelated prime and target words. A Remember/Forget cue, presented between the prime and target, designated the prime as TBR or TBF. When the cues were shown for 500 ms, targets preceded by Forget cues yielded a smaller P200 wave than those preceded by Remember cues. Furthermore, the topography of the N400 effect was different for targets preceded by Remember and Forget cues. The cues did not modulate the ERPs of the targets when they were shown for 1500 ms. Because P200 is sensitive to attention influence and the N400 effect reflects semantic processing, we conclude that forgetting is more effortful than remembering and that the semantic processing is different for TBR and TBF items. Nevertheless, there is a temporal limitation for the Remember/Forget cues to modulate the semantic processing and attentional resources in item-method directed forgetting. PMID- 22085679 TI - Protein-loaded PLGA-PEG-PLGA microspheres: a tool for cell therapy. AB - A promising strategy to repair injured organs is possible by delivering a growth factor via poly-(d,l lactide-co-glycolide) (PLGA) microspheres; the latter are coated with adhesion molecules that serve as a support for cell delivery. At present, PLGA is not the optimal choice of polymer because of poor or incomplete protein release. The use of a more hydrophilic PLGA-PEG-PLGA (A-B-A) copolymer increases the degree of protein release. In this work, the impact of different combinations of (B) and (A) segments on the protein-release profile has been investigated. Continuous-release profiles, with no lag phases, were observed. The triblock ABA with a low molecular weight of PEG and a high molecular weight of PLGA showed an interesting release pattern with a small burst (<10% in 48 h) followed by sustained, protein release over 36 days. Incomplete protein release was found to be due to various causes: protein adsorption, protein aggregation and protein denaturation under acidic conditions. Interestingly, cell viability and cell adhesion on microspheres coated with fibronectin highlight the interest of these polymers for tissue engineering applications. PMID- 22085680 TI - Carboxylated poly(glycerol methacrylate)s for doxorubicin delivery. AB - Poly(glycerol methacrylate)s (PGOHMAs) were successfully synthesized via the hydrolysis of the epoxy groups on linear and/or star-shaped poly(glycidyl methacrylate)s (PGMAs). Further modification of the hydroxyl groups on PGOHMAs with succinic anhydride (SA) or 1,2-cyclohexanedicarboxylic anhydride (CDA) resulted in a new type of polyacid polymer, namely, PGOHMACOOH for short, which was then employed to prepare pH-sensitive assemblies using dialysis method. The carboxylated polymers were quite effective in the encapsulation of doxorubicin hydrochloride (DOX) by electrostatic interaction. Compared with poly(acrylic acid) (PAA), the star-shaped PGOHMA modified with CDA exhibited higher encapsulation efficiency and loading capacity, as well as better pH-responsive release profile. Scanning electron microscope images showed that the polymeric nanoparticles before and after encapsulation of DOX were spherical in shape. The encapsulation efficiency, loading capacity and release properties of these polymers were found to rely on their backbone architectures and the type of carboxylated functionalities. By fine-tuning these factors to achieve optimal properties, such type of polymeric materials holds promise as an attractive and effective drug delivery vehicle. PMID- 22085681 TI - The concomitant use of an osmotic laxative, magnesium sulphate, and a stimulant laxative, bisacodyl, does not enhance the laxative effect. AB - Patients with severe constipation are treated with combinations of several different laxatives. The purpose of this study is to examine whether the concomitant use of different laxatives enhances the laxative effect, using an osmotic laxative, magnesium sulphate (MgSO4), and a stimulant laxative, bisacodyl. The faecal water content of rats, to which MgSO4 and bisacodyl were coadministered, was lower than that in the MgSO4 group, while the change in the faecal water content over time was very similar to that in the bisacodyl group. The mRNA expression of the osmotic pressure marker, sodium/myo-inositol transporter, in the coadministration group 5h after the administration was significantly higher than that in the control group and almost equal to that in the MgSO4 group. The protein expression level of aquaporin-3 (AQP3), which plays an important role in water transfer, in the coadministration group decreased compared to the control group, as was the case in the bisacodyl group. The results of this study indicates that the coadministration of MgSO4 and bisacodyl does not enhance the laxative effect because the expression level of AQP3 in the colon in the coadministration group was almost equal to that in the bisacodyl group. PMID- 22085682 TI - Tricin 7-glucoside protects against experimental cerebral ischemia by reduction of NF-kappaB and HMGB1 expression. AB - There have been several studies of nuclear factor-kappaB (NF-kappaB) and high mobility group box1 (HMGB1) associated with the pathophysiology of cerebral ischemia. Tricin 7-glucoside, a major bioactive compound extracted from Sedum sarmentosum Bunge. The objectives of this study were to determine the effects of Tricin 7-glucoside on a cultured neuronal cell line, SH-SY5Y in vitro and experimental ischemic stroke in vivo. For oxygen-glucose deprivation (OGD) and tumor necrosis factor-alpha (TNF-alpha) stimulated SH-SY5Y cell line in vitro, SH SY5Y cells were incubated with Tricin 7-glucoside. For in vivo experiment, rats were subjected to middle cerebral artery occlusion (MACO) for 1h, then followed by reperfusion for 23 h. Treatment of SH-SY5Y cells with Tricin 7-glucoside reduced the OGD-induced apoptosis and cytotoxicity, blocked TNF-alpha-induced NF kappaB and IkappaB-alpha phosphorylation, and decreased HMGB1 expression. At doses higher than 50mg/kg, Tricin 7-glucoside produced a significant neuroprotective potential in rats with ischemia and reperfusion (I/R). Tricin 7 glucoside (100mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 2h and 4h after I/R. Tricin 7-glucoside 100mg/kg attenuated histopathological damage, decreased brain edema, inhibited NF-kappaB activation and reduced HMGB1 expression. These data show that Tricin 7-glucoside protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and its protective effects may involve HMGB1 and NF-kappaB signaling pathway. PMID- 22085683 TI - Acupuncture as analgesia for low back pain, ankle sprain and migraine in emergency departments: study protocol for a randomized controlled trial. AB - BACKGROUND: Pain is the most common reason that patients present to an emergency department (ED) and is often inadequately managed. Evidence suggests that acupuncture is effective for pain relief, yet it is rarely practiced in the ED. The current study aims to assess the efficacy of acupuncture for providing effective analgesia to patients presenting with acute low back pain, migraine and ankle sprain at the EDs of four hospitals in Melbourne, Australia. METHOD: The study is a multi-site, randomized, assessor-blinded, controlled trial of acupuncture analgesia in patients who present to an ED with low back pain, migraine or ankle sprain. Patients will be block randomized to receive either acupuncture alone, acupuncture as an adjunct to pharmacotherapy or pharmacotherapy alone. Acupuncture will be applied according to Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Pain after one hour, measured using a visual analogue scale (VAS), is the primary outcome. Secondary outcomes measures include the following instruments; the Oswestry low back pain disability questionnaire, 24-hour Migraine Quality of Life questionnaire and Patient's Global Assessment of Ankle Injury Scale. These measures will be recorded at baseline, 1 hour after intervention, each hour until discharge and 48+/-12 hours of ED discharge. Data will also be collected on the safety and acceptability of acupuncture and health resource utilization. DISCUSSION: The results of this study will determine if acupuncture, alone or as an adjunct to pharmacotherapy provides effective, safe and acceptable pain relief for patients presenting to EDs with acute back pain, migraine or ankle sprain. The results will also identify the impact that acupuncture treatment may have upon health resource utilisation in the ED setting. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000989246. PMID- 22085684 TI - Imaging in gout--what can we learn from MRI, CT, DECT and US? AB - There are many exciting new applications for advanced imaging in gout. These modalities employ multiplanar imaging and allow computerized three-dimensional rendering of bone and joints (including tophi) and have the advantage of electronic data storage for later retrieval. High-resolution computed tomography has been particularly helpful in exploring the pathology of gout by investigating the relationship between bone erosions and tophi. Magnetic resonance imaging and ultrasonography can image the inflammatory nature of gouty arthropathy, revealing synovial and soft tissue inflammation, and can provide information about the composition and vascularity of tophi. Dual-energy computerized tomography is a new modality that is able to identify tophi by their chemical composition and reveal even small occult tophaceous deposits. All modalities are being investigated for their potential roles in diagnosis and could have important clinical applications in the patient for whom aspiration of monosodium urate crystals from the joint is not possible. Imaging can also provide outcome measures, such as change in tophus volume, for monitoring the response to urate lowering therapy and this is an important application in the clinical trial setting. PMID- 22085685 TI - Impact of the growing use of narrative verdicts by coroners on geographic variations in suicide: analysis of coroners' inquest data. AB - BACKGROUND: Coroners' death certificates form the basis of suicide statistics in England and Wales. Recent increases in coroners' use of narrative verdicts may affect the reliability of local and national suicide rates. METHOD: We used Ministry of Justice data on inquests held between 2008 and 2009 and Local Authority suicide data (2001-02 and 2008-09) to investigate variations between coroners in their use of narrative verdicts and the impact of these on suicide rates, using 'other' verdicts (79% of which are narratives) as a proxy for narrative verdicts. RESULTS: There was wide geographic variation in Coroners' use of 'other' (mainly narrative) verdicts--they comprised between 0 and 50% (median = 9%) of verdicts given by individual coroners in 2008-09. Coroners who gave more 'other' verdicts gave fewer suicide verdicts (r = - 0.41; P < 0.001). In the 10 English Coroners' jurisdictions where the highest proportion of 'other' verdicts were given, the incidence of suicide decreased by 16% between 2001-02 and 2008 09, whereas it did not change in areas served by the 10 coroners who used narratives the least. CONCLUSIONS: Variation in Coroners' use of narrative verdicts influences the validity of reported regional suicide rates. Small-area suicide rates, and changes in these rates over time in the last decade, should be interpreted with caution. PMID- 22085686 TI - Phenotype and transmission efficiency of artificial and natural male-killing Spiroplasma infections in Drosophila melanogaster. AB - Many insect species carry inherited Spiroplasma bacteria which act as important partners and antagonists. The nature of symbioses between Spiroplasma and insects has been most extensively studied in the interaction between male-killing Spiroplasma infection and Drosophila melanogaster. For historical reasons, these studies have largely focussed on the Spiroplasma strain known as NSRO, derived from Drosophila nebulosa and transinfected into D. melanogaster. More recently, D. melanogaster naturally infected with Spiroplasma were discovered. Whilst the well studied strain NSRO is closely related to that found natively in D. melanogaster, it is unclear whether strains from D. nebulosa reflect a natural interaction when placed in D. melanogaster. In this paper, we determine if NSRO has similar or different properties from strains of Spiroplasma naturally infecting D. melanogaster in terms of transmission efficiency and the strength and timing of male-killing. Native infections were observed to have higher transmission efficiency than introduced NSRO infections during the early phases of host reproduction, but not during late reproduction. The timing and intensity of male-killing did not differ between infection classes. As a precautionary measure, it is proposed that future work seeking to reveal the nature of coevolved Spiroplasma-Drosophila interactions use the native strain. PMID- 22085687 TI - Five-year outcome of major depressive disorder in primary health care. AB - BACKGROUND: Primary health care provides treatment for most patients with depression. Despite their importance for organizing services, long-term course of depression and risk factors for poor outcome in primary care are not well known. METHOD: In the Vantaa Primary Care Depression Study, a stratified random sample of 1119 patients representing primary care patients in a Finnish city was screened for depression with the Primary Care Evaluation of Mental Disorders. SCID-I/P and SCID-II interviews were used to diagnose Axis I and II disorders. The 137 patients with DSM-IV depressive disorder were prospectively followed up at 3, 6, 18 and 60 months. Altogether, 82% of patients completed the 5-year follow-up, including 102 patients with a research diagnosis of major depressive disorder (MDD) at baseline. Duration of the index episode, recurrences, time spent in major depressive episodes (MDEs) and partial or full remission were examined with a life-chart. RESULTS: Of the MDD patients, 70% reached full remission, in a median time of 20 months. One-third had at least one recurrence. The patients spent 34% of the follow-up time in MDEs, 24% in partial remission and 42% in full remission. Baseline severity of depression and substance use co morbidity predicted time spent in MDEs. CONCLUSIONS: This prospective, naturalistic, long-term study of a representative cohort of primary care patients with depression indicated slow or incomplete recovery and a commonly recurrent course, which need to be taken into account when developing primary care services. Severity of depressive symptoms and substance use co-morbidity should be systematically evaluated in planning treatment. PMID- 22085688 TI - Mizoribine--an inosine monophosphate dehydrogenase inhibitor--acts synergistically with cyclosporine A in prolonging survival of murine islet cell and heart transplants across major histocompatibility barrier. AB - INTRODUCTION: Mizoribine (MZR) is an inosine monophosphate dehydrogenase inhibitor. It has been widely used in Japan in the treatment of autoimmune diseases and is known to inhibit T and B cell proliferation. The aim of this study was to evaluate the efficacy of MZR as an immunosuppressive agent and determine its ability to synergize with a commonly used calcineurin inhibitor Cyclosporine A (CsA) in prolonging survival of murine islet cells and heart transplanted across major histocompatibility barrier. METHODS: Murine allogeneic islet cell transplantation between Balb/c donor mice and C57BL/6 recipient mice and heterotopic heart transplantation was done between C3H/He donor mice and Balb/c recipient mice. Recipients were divided into groups based on immunosuppression: Group 1-No immunosuppression, Group 2-MZR alone (20 mg/kg/day), Group 3-CsA alone (20 mg/kg/day), Group 4-MZR+CsA (20 mg/kg/day). Donor specific IFN-gamma, IL-10, IL-2, IL-4 secreting cells were enumerated by ELISpot. Serum cytokine and chemokine concentration was measured by Luminex. RESULTS: Islet cell allograft recipients treated with CsA and MZR had prolonged islet function compared to other groups [normoglycemia (blood glucose <200 mg/dL) up to 32+/-4 days, p<0.05]. Similarly, heart allograft survival was significantly improved in mice treated with CsA and MZR compared to other groups (50% 30-day survival, p=0.04). Donor specific IFN-gamma, IL-4, IL-2 secreting cells were significantly decreased in recipients treated with CsA and MZR with marked increase in IL-10 secreting cells (p<0.05). There was also an increase in serum IL-10 with decrease in IFN-gamma, IL-4, IL-2, MCP-1, and IL-6 in mice treated with CsA and MZR CONCLUSION: MZR and CsA when used in combination are potent immunosuppressive agents in murine islet cell and heart transplantation models. These agents lead to a decrease in donor specific IFN-gamma with increase in IL 10 secreting cells leading to improved allograft survival and function. PMID- 22085689 TI - Inductive expression of toll-like receptor 5 (TLR5) and associated downstream signaling molecules following ligand exposure and bacterial infection in the Indian major carp, mrigal (Cirrhinus mrigala). AB - Toll-like receptors (TLRs) are one of the key components of innate immunity. Among various types of TLRs, TLR5 is involved in recognizing bacterial flagellin and after binding, it triggers myeloid differentiation primary response gene 88 (MyD88)-dependent signaling pathway to induce pro-inflammatory cytokines. In this report, we analyzed the expression profile of TLR5 and its associated downstream signaling molecules like MyD88 and tumor necrosis factor (TNF) receptor associated factor (TRAF) 6 in the Indian major carp (IMC), mrigal (Cirrhinus mrigala) which is highly commercially important fish species in the Indian subcontinent. Ontogeny analysis of TLR5, MyD88 and TRAF6 revealed constitutive expression of these genes in all embryonic developmental stages, and highlighted the importance of embryonic innate immune defense system in fish. Tissue specific expression analysis of these genes by quantitative real-time PCR (qRT-PCR) revealed their wide distribution in various organs and tissues; highest expression of TLR5 and MyD88 was in liver and TRAF6 was in kidney. Modulation of TLR5, MyD88 and TRAF6 gene expression, and the induction of interleukin (IL)-8 and TNF-alpha were analyzed in various organs by qRT-PCR following flagellin stimulation, and Aeromonas hydrophila and Edwardsiella tarda infection. In the treated fish, majority of the tested tissues exhibited significant induction of these genes, although with varied intensity among the tissues and with the types of treatments. Among the examined tissues, a significant relationship of TLR5 induction, MyD88 and TRAF6 up-regulation, and enhanced expression of IL-8 and TNF alpha gene transcripts was observed in the blood and intestine of both flagellin stimulated and bacteria infected fish. These findings may indicate the involvement of TLR5 in inducing IL-8 and TNF-alpha, and suggest the important role of TLR5 in augmenting innate immunity in fish in response to pathogenic invasion. This study will enrich the information in understanding the innate immune mechanism in fish and may be helpful in developing preventive measures against infectious diseases in fish. PMID- 22085690 TI - Macrophages-mediated neurotoxic effects of intra-nigral manganese administration are attenuated by minocycline. AB - The present study was designed to address the role of macrophages in Mn-induced neurotoxicity and to test the hypothesis that minocycline, a tetracycline derivative, attenuates the biochemical and morphological sequelae of Mn. Mn was unilaterally microinjected into rat nigra followed by systemic minocycline or saline administration 24h later, daily for 3 days. At 72h after the intranigral Mn microinjection, tyrosine hydroxylase immunostaining (TH-IS) was evaluated in the striatum, along with the number of macrophages (as indicated by CD11b immunostaining) in the substantia nigra. Mn significantly reduced striatal TH-IS, and causes an increased macrophage number at the lesion site when compared with the control group. The effects of Mn on striatal TH-IS and the number of macrophages at the lesion site were concentration dependent. Consistent with the stated hypothesis, minocycline significantly reduced the macrophage number in the lesion site and minimized the TH-IS striatal loss induced by Mn. These results indicate that an inflammatory response mediated by macrophages is induced by intranigral Mn microinjection, which is fully attenuated by minocycline treatment, suggesting that suppression of macrophage infiltration provides neuroprotection to dopaminergic neurons. PMID- 22085691 TI - Modeling the gait of normal and Parkinsonian persons for improving the diagnosis. AB - In this study, we present a model for the gait of normal and Parkinson's disease (PD) persons. Gait is semi-periodic and has fractal properties. Sine circle map (SCM) relation has a sinusoidal term and can show chaotic behaviour. Therefore, we used SCM as a basis for our model structure. Moreover, some similarities exist between the parameters of this relation and basal ganglia (BG) structure. This relation can explain the complex behaviours and the complex structure of BG. The presented model can simulate the BG behaviour globally. A model parameter, Omega, has a key role in the model response. We showed that when Omega is between 0.6 and 0.8, the model simulates the behaviour of normal persons; the amounts greater or less than this range correspond to PD persons. Our statistical tests show that there is a significant difference between the Omega of normal and PD patients. We conclude that Omega can be introduced as a parameter to distinguish normal and PD persons. Additionally, our results showed that Spearman correlation between the Omega and the severity of PD is 0.586. This parameter may be a good index of PD severity. PMID- 22085692 TI - Sensory feedback prosthesis reduces phantom limb pain: proof of a principle. AB - BACKGROUND: Constrained functionality and phantom limb pain (PLP) are major concerns for forearm amputees. Neuroscientific investigations of PLP suggest that behaviorally relevant stimulation of the stump can decrease PLP. Furthermore the prosthesis user could use feedback information of the prosthesis hand for optimizing prosthesis motor control when handling soft and fragile objects. Somatosensory feedback information from a prosthetic hand may therefore help to improve prosthesis functionality and reduce phantom limb pain. OBJECTIVES: We wanted to find out whether a two weeks training on a hand prosthesis that provides somatosensory feedback may help to improve prosthesis functionality and reduce phantom limb pain. METHODS: Eight forearm amputees with phantom limb pain were trained for two weeks to use a hand prosthesis with somatosensory feedback on grip strength. RESULTS: The current study demonstrates a significant increase of functionality of the prosthesis in everyday tasks. Furthermore, the study shows that usage of a prosthesis that provides somatosensory feedback on the grip strength is effective to reduce phantom limb pain. CONCLUSIONS: A prosthesis with a feedback function appears to be a promising therapeutic tool to reduce phantom limb pain and to increase functionality in everyday tasks. Future studies should further investigate the scope of application of that principle. PMID- 22085693 TI - Optineurin in Huntington's disease intranuclear inclusions. AB - Optineurin mutations cause adult-onset primary open-angle glaucoma and have been associated with some familial forms of amyotrophic lateral sclerosis (ALS). Optineurin is involved in many cellular processes and interacts with a variety of proteins, among them huntingtin (htt). Here we report that in Huntington's disease (HD) cortex, optineurin frequently occurs in neuronal intranuclear inclusions, and to a lesser extent, in inclusions in the neuropil and in perikarya. Most intranuclear optineurin-positive inclusions were co-labeled for ubiquitin, but they were only occasionally and more weakly co-labeled for htt. Optineurin-labeled neuropil and perikaryal inclusions were commonly co-labeled for ubiquitin and htt. Although these inclusions were common in cortex, they were rare in striatum. Our results show that in HD optineurin is present in intranuclear, neuropil and perikaryal inclusions. It is not clear whether this indicates a primary involvement in the disease process. In HD, the known interaction of htt and optineurin may suggest that a different process takes place as compared to other neurodegenerative disorders. PMID- 22085694 TI - Impaired long-trace eyeblink conditioning in a Tg2576 mouse model of Alzheimer's disease. AB - Eyeblink conditioning has been used for assessing cognitive performance in cases of human neurodegenerative diseases including Alzheimer's disease (AD). Here, we tested and compared the delay and long-trace interval (TI=500ms) eyeblink conditionings in a Tg2576 mouse model of AD, at the age of 3, 6, and 12 months. Tg2576 mice exhibited significant impairment in trace conditioning at 6 months of age. In contrast, delay conditioning was not impaired in Tg2576 mice even at 12 months. These findings indicate that the long-TI eyeblink conditioning is more susceptible to age-related cognitive deterioration than delay conditioning in Tg2576 mice. The long-trace eyeblink conditioning could be a potential tool for detecting early cognitive deficits in AD mouse model. PMID- 22085695 TI - Membrane resonance and its ionic mechanisms in rat subthalamic nucleus neurons. AB - The oscillatory activity in the basal ganglia is believed to have an important function, but little is known about its actual mechanisms. We studied the resonance characteristics of subthalamic nucleus (STN) neurons and their ionic mechanisms using whole-cell patch-clamp recordings in rat brain slices. A swept sine-wave current with constant amplitude and linearly increasing frequency was applied to measure the resonance frequency (f(res)) of STN neurons. We also used single-frequency sine wave current to evoke firing. We found that the resonance of STN neurons was temperature- and voltage-dependent. The f(res) of STN neurons was about 4Hz when the temperature was maintained at 38 degrees C and holding potential was at -70mV. The f(res) increased with more negative holding potentials and decreased with lower temperature. Action potentials fired most readily when the input frequency was near f(res). After application of drug ZD7288 (20MUM), the resonance of STN neurons was blocked and the spikes evoked by both impedance amplitude profile (ZAP) current and single-frequency sine wave current arose readily at the lowest frequencies, indicating that hyperpolarization-activated cation current (I(h)) generated the resonance and mediated a preferential coupling at frequencies near f(res) between inputs and firing. In conclusion, there is a theta-frequency resonance mediated by I(h) in STN neurons. The resonance characteristics are temperature- and voltage dependent. The resonance mediates a frequency-selective coupling between inputs and firing. PMID- 22085696 TI - The anatomical characteristics of superior longitudinal fasciculus I in human brain: Diffusion tensor tractography study. AB - The superior longitudinal fasciculus (SLF) I is known to be involved in regulation of higher aspects of motor function. Using diffusion tensor imaging (DTI), we attempted to identify the SLF I and to investigate the anatomical characteristics of the SLF I in the human brain. We recruited 30 healthy subjects for this study. The SLF I was obtained using the FMRIB Software Library. The seed region of interest (ROI) was given at the superior parietal lobule (SPL) and the target ROI was the supplementary motor area (SMA) along with the dorsal part of the premotor area (PMA). Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume were measured. The SLF I originated from the SPL and medial parietal cortex, passed through the white matter of the SPL and superior frontal gyrus, and then terminated in the SMA and dorsal PMA. There were no significant differences between hemispheres in terms of the FA, MD, and tract volume. We present with the anatomical characteristics of the SLF I in the human brain using DTI. We think that the methodology and results of this study would be helpful to researchers in this field. PMID- 22085697 TI - Subjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers. AB - Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substances Act. The subjective effects of this drug have not been well characterized, and the extent to which it alters the subjective effects of opioids has not been studied to the best of our knowledge. Using a double-blind, randomized, crossover design, 16 healthy volunteers were administered (in separate sessions) capsules containing placebo, 75 mg pregabalin, 150 mg pregabalin, 10 mg oxycodone, and 75 mg pregabalin combined with 10 mg oxycodone. Subjective, psychomotor, and physiological measures were assessed during each of the five sessions. Pregabalin produced dose-related increases in some subjective effects and decreased respiration rate, but did not impact on psychomotor performance. Abuse liability-related subjective effects such as drug liking and desire to take the drug again were not increased by either pregabalin dose. Oxycodone produced increases in several subjective effects, including ratings of drug liking. When 75 mg pregabalin was combined with oxycodone some subjective effects were altered relative to placebo, in contrast to when each drug was tested alone. Liking of oxycodone was not increased by 75 mg pregabalin. However, recent studies have suggested that this drug is abused, and we would recommend that further psychopharmacological studies with pregabalin are warranted, including a study assessing its abuse liability across a range of doses in sedative abusers. PMID- 22085698 TI - Enhancing clinical concept extraction with distributional semantics. AB - Extracting concepts (such as drugs, symptoms, and diagnoses) from clinical narratives constitutes a basic enabling technology to unlock the knowledge within and support more advanced reasoning applications such as diagnosis explanation, disease progression modeling, and intelligent analysis of the effectiveness of treatment. The recent release of annotated training sets of de-identified clinical narratives has contributed to the development and refinement of concept extraction methods. However, as the annotation process is labor-intensive, training data are necessarily limited in the concepts and concept patterns covered, which impacts the performance of supervised machine learning applications trained with these data. This paper proposes an approach to minimize this limitation by combining supervised machine learning with empirical learning of semantic relatedness from the distribution of the relevant words in additional unannotated text. The approach uses a sequential discriminative classifier (Conditional Random Fields) to extract the mentions of medical problems, treatments and tests from clinical narratives. It takes advantage of all Medline abstracts indexed as being of the publication type "clinical trials" to estimate the relatedness between words in the i2b2/VA training and testing corpora. In addition to the traditional features such as dictionary matching, pattern matching and part-of-speech tags, we also used as a feature words that appear in similar contexts to the word in question (that is, words that have a similar vector representation measured with the commonly used cosine metric, where vector representations are derived using methods of distributional semantics). To the best of our knowledge, this is the first effort exploring the use of distributional semantics, the semantics derived empirically from unannotated text often using vector space models, for a sequence classification task such as concept extraction. Therefore, we first experimented with different sliding window models and found the model with parameters that led to best performance in a preliminary sequence labeling task. The evaluation of this approach, performed against the i2b2/VA concept extraction corpus, showed that incorporating features based on the distribution of words across a large unannotated corpus significantly aids concept extraction. Compared to a supervised-only approach as a baseline, the micro-averaged F-score for exact match increased from 80.3% to 82.3% and the micro-averaged F-score based on inexact match increased from 89.7% to 91.3%. These improvements are highly significant according to the bootstrap resampling method and also considering the performance of other systems. Thus, distributional semantic features significantly improve the performance of concept extraction from clinical narratives by taking advantage of word distribution information obtained from unannotated data. PMID- 22085699 TI - Sensitization of epithelial growth factor receptors by nicotine exposure to promote breast cancer cell growth. AB - INTRODUCTION: Tobacco smoke is known to be the main cause of lung, head and neck tumors. Recently, evidence for an increasing breast cancer risk associated with tobacco smoke exposure has been emerging. We and other groups have shown that nicotine, as a non-conventional carcinogen, has the potential to facilitate cancer genesis and progression. However, the underlying mechanisms by which the smoke affects the breast, rather than the lung, remain unclear. Here, we examine possible downstream signaling pathways of the nicotinic acetylcholine receptor (nAChR) and their role in breast cancer promotion. METHODS: Using human benign MCF10A and malignant MDA-MB-231 breast cells and specific inhibitors of possible downstream kinases, we identified nAChR effectors that were activated by treatment with nicotine. We further tested the effects of these effector pathways on the regulation of E2F1 activation, cell cycle progression and on Bcl-2 expression and long-term cell survival. RESULTS: In this study, we demonstrated a novel signaling mechanism by which nicotine exposure activated Src to sensitize epidermal growth factor receptor (EGFR)-mediated pathways for breast cancer cell growth promotion. After the ligation of nAChR with nicotine, EGFR was shown to be activated and then internalized in both MCF10A and MDA-MB-231 breast cancer cells. Subsequently, Src, Akt and ERK1/2 were phosphorylated at different time points following nicotine treatment. We further demonstrated that through Src, the ligation of nicotine with nAChR stimulated the EGFR/ERK1/2 pathway for the activation of E2F1 and further cell progression. Our data also showed that Akt functioned directly downstream of Src and was responsible for the increase of Bcl 2 expression and long-term cell survival. CONCLUSIONS: Our study reveals the existence of a potential, regulatory network governed by the interaction of nicotine and nAChR that integrates the conventional, mitogenic Src and EGFR signals for breast cancer development. PMID- 22085700 TI - Frameless linac-based stereotactic radiosurgery (SRS) for brain metastases: analysis of patient repositioning using a mask fixation system and clinical outcomes. AB - PURPOSE: To assess the accuracy of patient repositioning and clinical outcomes of frameless stereotactic radiosurgery (SRS) for brain metastases using a stereotactic mask fixation system. PATIENTS AND METHODS: One hundred two patients treated consecutively with frameless SRS as primary treatment at University of Rome Sapienza Sant'Andrea Hospital between October 2008 and April 2010 and followed prospectively were involved in the study. A commercial stereotactic mask fixation system (BrainLab) was used for patient immobilization. A computerized tomography (CT) scan obtained immediately before SRS was used to evaluate the accuracy of patient repositioning in the mask by comparing the isocenter position to the isocenter position established in the planning CT. Deviations of isocenter coordinates in each direction and 3D displacement were calculated. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. RESULTS: The mean measured isocenter displacements were 0.12 mm (SD 0.35 mm) in the lateral direction, 0.2 mm (SD 0.4 mm) in the anteroposterior, and 0.4 mm (SD 0.6 mm) in craniocaudal direction. The maximum displacement of 2.1 mm was seen in craniocaudal direction. The mean 3D displacement was 0.5 mm (SD 0.7 mm), being maximum 2.9 mm. The median survival was 15.5 months, and 1-year and 2-year survival rates were 58% and 24%, respectively. Nine patients recurred locally after SRS, with 1-year and 2-year local control rates of 91% and 82%, respectively. Stable extracranial disease (P = 0.001) and KPS > 70 (P = 0.01) were independent predictors of survival. CONCLUSIONS: Frameless SRS is an effective treatment in the management of patients with brain metastases. The presented non-invasive mask-based fixation stereotactic system is associated with a high degree of patient repositioning accuracy; however, a careful evaluation is essential since occasional errors up to 3 mm may occur. PMID- 22085701 TI - A flexible framework for sparse simultaneous component based data integration. AB - BACKGROUND: High throughput data are complex and methods that reveal structure underlying the data are most useful. Principal component analysis, frequently implemented as a singular value decomposition, is a popular technique in this respect. Nowadays often the challenge is to reveal structure in several sources of information (e.g., transcriptomics, proteomics) that are available for the same biological entities under study. Simultaneous component methods are most promising in this respect. However, the interpretation of the principal and simultaneous components is often daunting because contributions of each of the biomolecules (transcripts, proteins) have to be taken into account. RESULTS: We propose a sparse simultaneous component method that makes many of the parameters redundant by shrinking them to zero. It includes principal component analysis, sparse principal component analysis, and ordinary simultaneous component analysis as special cases. Several penalties can be tuned that account in different ways for the block structure present in the integrated data. This yields known sparse approaches as the lasso, the ridge penalty, the elastic net, the group lasso, sparse group lasso, and elitist lasso. In addition, the algorithmic results can be easily transposed to the context of regression. Metabolomics data obtained with two measurement platforms for the same set of Escherichia coli samples are used to illustrate the proposed methodology and the properties of different penalties with respect to sparseness across and within data blocks. CONCLUSION: Sparse simultaneous component analysis is a useful method for data integration: First, simultaneous analyses of multiple blocks offer advantages over sequential and separate analyses and second, interpretation of the results is highly facilitated by their sparseness. The approach offered is flexible and allows to take the block structure in different ways into account. As such, structures can be found that are exclusively tied to one data platform (group lasso approach) as well as structures that involve all data platforms (Elitist lasso approach). AVAILABILITY: The additional file contains a MATLAB implementation of the sparse simultaneous component method. PMID- 22085702 TI - Ethics in practice: the state of the debate on promoting the social value of global health research in resource poor settings particularly Africa. AB - BACKGROUND: Promoting the social value of global health research undertaken in resource poor settings has become a key concern in global research ethics. The consideration for benefit sharing, which concerns the elucidation of what if anything, is owed to participants, their communities and host nations that take part in such research, and the obligations of researchers involved, is one of the main strategies used for promoting social value of research. In the last decade however, there has been intense debate within academic bioethics literature seeking to define the benefits, the beneficiaries, and the scope of obligations for providing these benefits. Although this debate may be indicative of willingness at the international level to engage with the responsibilities of researchers involved in global health research, it remains unclear which forms of benefits or beneficiaries should be considered. International and local research ethics guidelines are reviewed here to delineate the guidance they provide. METHODS: We reviewed documents selected from the international compilation of research ethics guidelines by the Office for Human Research Protections under the US Department of Health and Human Services. RESULTS: Access to interventions being researched, the provision of unavailable health care, capacity building for individuals and institutions, support to health care systems and access to medical and public health interventions proven effective, are the commonly recommended forms of benefits. The beneficiaries are volunteers, disease or illness affected communities and the population in general. Interestingly however, there is a divide between "global opinion" and the views of particular countries within resource poor settings as made explicit by differences in emphasis regarding the potential benefits and the beneficiaries. CONCLUSION: Although in theory benefit sharing is widely accepted as one of the means for promoting the social value of international collaborative health research, there is less agreement amongst major guidelines on the specific responsibilities of researchers over what is ethical in promoting the social value of research. Lack of consensus might have practical implications for efforts aimed at enhancing the social value of global health research undertaken in resource poor settings. Further developments in global research ethics require more reflection, paying attention to the practical realities of implementing the ethical principles in real world context. PMID- 22085704 TI - A novel approach to prevent endothelial hyperpermeability: the Crataegus extract WS(r) 1442 targets the cAMP/Rap1 pathway. AB - Endothelial hyperpermeability followed by edema formation is a hallmark of many severe disorders. Effective drugs directly targeting endothelial barrier function are widely lacking. We hypothesized that the hawthorn (Crataegus spp.) extract WS(r) 1442, a proven multi-component drug against moderate forms of heart failure, would prevent vascular leakage by affecting endothelial barrier regulating systems. In vivo, WS(r) 1442 inhibited the histamine-evoked extravasation of FITC-dextran from mouse cremaster muscle venules. In cultured human endothelial cells, WS(r) 1442 blocked the thrombin-induced FITC-dextran permeability. By applying biochemical and microscopic techniques, we revealed that WS(r) 1442 abrogates detrimental effects of thrombin on adherens junctions (vascular endothelial-cadherin), the F-actin cytoskeleton, and the contractile apparatus (myosin light chain). Mechanistically, WS(r) 1442 inhibited the thrombin-induced rise of intracellular calcium (ratiometric measurement), followed by an inactivation of PKC and RhoA (pulldown assay). Moreover, WS(r) 1442 increased endothelial cAMP levels (ELISA), which consequently activated PKA and Rap1 (pulldown assay). Utilizing pharmacological inhibitors or siRNA, we found that PKA is not involved in barrier protection, whereas Epac1, Rap1, and Rac1 play a crucial role in the WS(r) 1442-induced activation of cortactin, which triggers a strong cortical actin rearrangement. In summary, WS(r) 1442 effectively protects against endothelial barrier dysfunction in vitro and in vivo. It specifically interacts with endothelial permeability-regulating systems by blocking the Ca(2+)/PKC/RhoA and activating the cAMP/Epac1/Rap1 pathway. As a proven safe herbal drug, WS(r) 1442 opens a novel pharmacological approach to treat hyperpermeability-associated diseases. This in-depth mechanistic work contributes to a better acceptance of this herbal remedy. PMID- 22085703 TI - Back to your heart: ubiquitin proteasome system-regulated signal transduction. AB - Awareness of the regulation of cell signaling by post-translational ubiquitination has emerged over the past 2 decades. Like phosphorylation, post translational modification of proteins with ubiquitin can result in the regulation of numerous cellular functions, for example, the DNA damage response, apoptosis, cell growth, and the innate immune response. In this review, we discuss recently published mechanisms by which the ubiquitin proteasome system regulates key signal transduction pathways in the heart, including MAPK JNK, calcineurin, FOXO, p53, and estrogen receptors alpha and beta. We then explore how ubiquitin proteasome system-specific regulation of these signal transduction pathways plays a role in the pathophysiology of common cardiac diseases, such as cardiac hypertrophy, heart failure, ischemia reperfusion injury, and diabetes. This article is part of a Special Section entitled "Post-translational Modification." PMID- 22085705 TI - Treatment of depressive disorders in primary care--protocol of a multiple treatment systematic review of randomized controlled trials. AB - BACKGROUND: Several systematic reviews have summarized the evidence for specific treatments of primary care patients suffering from depression. However, it is not possible to answer the question how the available treatment options compare with each other as review methods differ. We aim to systematically review and compare the available evidence for the effectiveness of pharmacological, psychological, and combined treatments for patients with depressive disorders in primary care. METHODS/DESIGN: To be included, studies have to be randomized trials comparing antidepressant medication (tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), hypericum extracts, other agents) and/or psychological therapies (e.g. interpersonal psychotherapy, cognitive therapy, behavioural therapy, short dynamically-oriented psychotherapy) with another active therapy, placebo or sham intervention, routine care or no treatment in primary care patients in the acute phase of a depressive episode. Main outcome measure is response after completion of acute phase treatment. Eligible studies will be identified from available systematic reviews, from searches in electronic databases (Medline, Embase and Central), trial registers, and citation tracking. Two reviewers will independently extract study data and assess the risk of bias using the Cochrane Collaboration's corresponding tool. Meta-analyses (random effects model, inverse variance weighting) will be performed for direct comparisons of single interventions and for groups of similar interventions (e.g. SSRIs vs. tricyclics) and defined time-windows (up to 3 months and above). If possible, a global analysis of the relative effectiveness of treatments will be estimated from all available direct and indirect evidence that is present in a network of treatments and comparisons. DISCUSSION: Practitioners do not only want to know whether there is evidence that a specific treatment is more effective than placebo, but also how the treatment options compare to each other. Therefore, we believe that a multiple treatment systematic review of primary-care based randomized controlled trials on the most important therapies against depression is timely. PMID- 22085706 TI - Physical activity and dietary behavior change in Internet-based weight loss interventions: comparing two multiple-behavior change indices. AB - OBJECTIVE: To investigate the effects of two Internet-based weight loss interventions on physical activity (PA) and dietary behaviors using two approaches for computing combined behavior change. METHOD: Participants were 352 overweight/obese women and men completing 12-month interventions in San Diego, California during 2002-2007. Moderate-to-vigorous PA (MVPA) and sedentary time were measured with accelerometers, and dietary fat and fruit and vegetable intake were assessed with food frequency questionnaires. Longitudinal analyses tested the effect of the intervention on combined health behavior change quantified using a standardized residualized change index (SRCI) and a risk factor change index (RFCI). RESULTS: At baseline, participants engaged in an average of 153 min/week of MVPA and 525 min/day of sedentary time, and consumed 37% of calories from fat and <3 fruits and vegetables per day. The interventions had a significant effect on combined behavior change as measured with each approach (p<0.001). The intervention effect was larger (p<0.001) when evaluated using the SRCI (standardized regression coefficient [Beta]=0.30) than the RFCI (beta= 0.18). CONCLUSION: Interventions that target both PA and dietary behaviors appear effective. The SRCI was more sensitive for evaluating the intervention, but the RFCI may be easier to use for communicating public health significance. PMID- 22085708 TI - A comparison of the spatiotemporal parameters, kinematics, and biomechanics between shod, unshod, and minimally supported running as compared to walking. AB - Recreational running has many proven benefits which include increased cardiovascular, physical and mental health. It is no surprise that Running USA reported over 10 million individuals completed running road races in 2009 not to mention recreational joggers who do not wish to compete in organized events. Unfortunately there are numerous risks associated with running, the most common being musculoskeletal injuries attributed to incorrect shoe choice, training errors and excessive shoe wear or other biomechanical factors associated with ground reaction forces. Approximately 65% of chronic injuries in distance runners are related to routine high mileage, rapid increases in mileage, increased intensity, hills or irregular surface running, and surface firmness. Humans have been running barefooted or wearing minimally supportive footwear such as moccasins or sandals since the beginning of time while modernized running shoes were not invented until the 1970s. However, the current trend is that many runners are moving back to barefoot running or running in "minimal" shoes. The goal of this masterclass article is to examine the similarities and differences between shod and unshod (barefoot or minimally supportive running shoes) runners by examining spatiotemporal parameters, energetics, and biomechanics. These running parameters will be compared and contrasted with walking. The most obvious difference between the walking and running gait cycle is the elimination of the double limb support phase of walking gait in exchange for a float (no limb support) phase. The biggest difference between barefoot and shod runners is at the initial contact phase of gait where the barefoot and minimally supported runner initiates contact with their forefoot or midfoot instead of the rearfoot. As movement science experts, physical therapists are often called upon to assess the gait of a running athlete, their choice of footwear, and training regime. With a clearer understanding of running and its complexities, the physical therapist will be able to better identify faults and create informed treatment plans while rehabilitating patients who are experiencing musculoskeletal injuries due to running. PMID- 22085709 TI - Altered leg muscle activity in volleyball players with functional ankle instability during a sideward lateral cutting movement. AB - OBJECTIVES: To study the activation patterns of tibialis anterior, peroneus longus and gastrocnemius lateralis muscles during a lateral shuffle maneuver in volleyball players with functional instability of the ankle joint. DESIGN: Observational case-control study. SETTING: Research laboratory. PARTICIPANTS: Sixteen players with functional instability and 18 matched controls. MAIN OUTCOME MEASURES: RMS values of tibialis anterior, peroneus longus and gastrocnemius lateralis muscles for the 50 ms before initial ground contact, timing of onset of muscle activity and linear envelopes for the period of ground contact were calculated. RESULTS: Onset values showed similar patterns of activation for both groups. In healthy subjects, gastrocnemius lateralis activated earlier, followed by peroneus longus and tibialis anterior. In the unstable subjects, gastrocnemius lateralis and peroneus longus activated at the same time, followed by tibialis anterior. Unstable subjects also presented lower peroneus longus activity during the 50 ms before initial ground impact, a lower peroneus longus peak magnitude and a higher gastrocnemius lateralis peak magnitude. CONCLUSIONS: Volleyball players with ankle functional instability showed decreased peroneus longus activity before ground impact that may predispose them to repetitive sprains and explain their "giving way" sensation, since peroneus longus is the main ankle evertor and an important stabilizer against sudden and excessive inversion. PMID- 22085710 TI - Comparison of lateral abdominal muscle thickness between weightlifters and matched controls. AB - OBJECTIVE: To compare lateral abdominal muscle thickness between weightlifters and matched controls. DESIGN: A case control study design. SETTING: University laboratory. SUBJECTS: 16 female Thai national weightlifters and 16 matched controls participated in this study. MAIN OUTCOME MEASURES: Ultrasound imaging with a 12-MHz linear array was used to measure the resting thickness of transversus abdominis (TrA), internal oblique (IO) and total thickness (Total) of lateral abdominal muscle (LAM) on the right side of abdominal wall. The absolute muscle thickness and the relative contribution of each muscle to the total thickness were determined. RESULTS: Weightlifters had significantly thicker absolute TrA and IO muscles than matched controls (p < 0.01). Further, the relative thickness of the IO was significantly greater in weightlifters than matched controls (p < 0.05). CONCLUSIONS: The findings of this study suggest that routine Olympic style weight training among female weightlifters appears to result in preferential hypertrophy or adaptation of the IO muscle. PMID- 22085711 TI - Criterion-related validity of four clinical tests used to measure hamstring flexibility in professional futsal players. AB - OBJECTIVE: To examine the criterion related validity of the sit-and-reach test (SR), toe touch test (TT), modified sit-and-reach test (MSR) and back-saver sit and-reach test (BSSR) for estimating hamstring flexibility measured through the passive straight leg raise test (PSLR) in professional futsal players. DESIGN: Correlation laboratory study. SETTING: Controlled laboratory environment. PARTICIPANTS: One hundred and three futsal players (55 males age 26 +/- 4 years, 48 females age 23 +/- 5 years). MAIN OUTCOME MEASURES: Two trials of SR, TT, MSR, BSSR (left and right) and PSLR right and left (hamstring criterion measure) in a randomized order. RESULTS: Regression analysis was performed to examine the association of SR, TT, MSR and BSSR with PSLR in both males and females separately. In males, only MSR test had moderate association criterion with PSLR (R(2) = 0.57). In females, SR (R(2) = 0.86), TT (R(2) = 0.85), MSR (R(2) = 0.53) and average BSSR (R(2) = 0.82) were associated with PSLR. CONCLUSIONS: SR, TT, MSR and BSSR had moderate criterion related validity for estimating hamstring flexibility in female but not male professional futsal players. The authors recommend that researchers, clinicians, and physical therapists adopt one angular test as a measure of hamstring muscle length in futsal players. PMID- 22085712 TI - Effectiveness of regular proactive massage therapy for novice recreational runners. AB - OBJECTIVES: To assess effects of a regular massage program on novice runners over a longer-term training period. PARTICIPANTS: Twelve control and sixteen massage subjects took part in the study. SETTING: Both groups participated in 10-week running preparation clinics. DESIGN: An individualized massage treatment plan was developed for each massage group participant. Massage group subjects met weekly with a registered massage therapist for a half hour massage. Control subjects were given no massage treatments. MAIN OUTCOME MEASURES: All participants maintained a running journal that recorded running behavior: frequency, distance, intensity, and pain. At weeks 1, 5, and 10, muscle strength, leg pain, daily functioning, and running confidence were assessed. RESULTS: The running behavior of both groups was similar (p > 0.05). Both groups experienced a considerable amount of pain when they ran. However, 100% of the massage group compared to 58.3% of control group completed the 10 km race. CONCLUSIONS: A regular massage therapy program during training did not improve indices of muscle strength, pain perception, daily functioning or running confidence. However, the entire massage group met their targeted running goals while only half of the control was able to do so however this difference may not be attributable to the massage intervention. PMID- 22085713 TI - The effect of first ballet classes in the community on various postural parameters in young girls. AB - OBJECTIVE: To examine the effect of first season ballet classes in the community on the thoracic kyphosis (TK), lumbar lordosis (LL), hip external rotation (ER) and joint flexibility in young girls. DESIGN: Longitudinal single blinded cohort control study. SETTING: Institutional. PARTICIPANTS: 30 girls aged 6-9, recruited from the same primary school were divided equally into 2 groups: a group bi weekly community ballet class and a sedentary control group. INTERVENTION: All girls were assessed prior to ballet classes (t(0)), at the conclusion (t(1)) (6 months), and approximately one year later (t(fu)). MAIN OUTCOME MEASURES: Beighton score for joint hyper-flexibility, peak of TK and LL, range of hip ER, ratio TK/LL, and individual's height, weight and BMI. RESULTS: LL at t1 became greater in the ballet girls' group (23.7 degrees +/- 6) as opposed to the controls (19.5 degrees +/-3.9) due to a decrease in LL in the controls from t0 to t1 (mean difference = -16.5 degrees ) (cut-off score = 3.45 degrees ) (p < 0.05). TK decreased from t0 to t1 in the ballet girls' group (mean difference = -26.1 degrees ) and controls (mean difference = -31.3 degrees ) (cut-off score = 4.85 degrees ) (p < 0.05). Left hip ER decreased only in the controls from t0 to t1 (mean difference = -13.8 degrees ) (cut-off score = 5.43 degrees ) (p < 0.05). Beighton score at tfu was greater in the ballet girls' group (6.1 +/- 2.3) as opposed to the controls (4.4 +/- 1.5) (p < 0.05). CONCLUSIONS: First season ballet classes for young girls in the community can be associated with relatively greater LL, and left hip ER and joint hyper-flexibility. PMID- 22085714 TI - Correlation of single leg vertical jump, single leg hop for distance, and single leg hop for time. AB - OBJECTIVES: To determine the correlation among three functional tests: single leg vertical jump (SLVJ), single leg hop for distance (SLHD), and single leg hop for time (SLHT). DESIGN: Prospective correlational investigation. SETTING: University research laboratory. PARTICIPANTS: Forty healthy men (n = 19) and women (n = 21) between the ages of 18 and 30 (23.9 +/- 2.0 years). MAIN OUTCOME MEASURES: SLVJ was measured using the Vertec. SLHD was measured using a standard tape measure. SLHT was measured over a 10-m course using a standard stopwatch. RESULTS: The strongest correlation was between SLHT and SLHD, -0.89 and -0.89 for dominant and non-dominant lower extremities (LE), respectively. The weakest pairwise correlation was between SLVJ and SLHT, -0.71 and -0.63 for dominant and non dominant LE, respectively. The correlation between SLVJ and SLHD was 0.74 and 0.71 for dominant and non-dominant LE, respectively. CONCLUSION: There is a strong correlation between SLHT and SLHD, suggesting that each test measures similar constructs of function, while the modest correlation between SLVJ and SLHT suggest these two tests do not measure the same functional components, and could be paired as outcome measures for the clinical assessment of lower extremity function. PMID- 22085715 TI - Muscle onset can be improved by therapeutic exercise: a systematic review. AB - OBJECTIVES: To determine whether therapeutic exercise can improve the timing of muscle onset following musculoskeletal pathology, and examine what exercise prescription parameters are being used to achieve these effects. PARTICIPANTS: People with a musculoskeletal pathology. MAIN OUTCOME MEASURE: Muscle onset timing as measured by electromyography. RESULTS: Sixteen investigations were identified containing 19 therapeutic exercise groups. Three exercise modes were identified including: isolated muscle training, instability training, and general strength training. Isolated muscle training is consistently shown to have a positive effect on the muscle onset timing of transversus abdominus in people with low back pain. There is some evidence from cohort studies that instability training may change muscle onset timing in people with functional ankle instability, however controlled trials suggest that no effect is present. General strength training shows no effect on muscle onset timing in people with low back or neck pain, although one cohort study suggests that a positive effect on gluteus maximus may be present in people with low back pain. CONCLUSION: Therapeutic exercise training is likely to improve muscle onset timing. Additionally, isolated muscle training appears to be the best exercise mode to use to achieve these effects. PMID- 22085716 TI - Potent and selective inhibition of hepatitis C virus replication by novel phenanthridinone derivatives. AB - A number of novel phenanthridinone derivatives were examined for their inhibitory effect on hepatitis C virus (HCV) replication in Huh-7 cells harboring self replicating subgenomic viral RNA replicons with a luciferase reporter (LucNeo#2). The activity of compounds was further confirmed by inhibition of viral RNA copy number in different subgenomic and full-genomic replicon cells using real-time reverse transcription polymerase chain reaction. Among the compounds, 4-butyl-11 (1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-7-methoxy-[1,3]dioxolo[4,5 c]phenanthridin-5(4H)-one (HA-719) was found to be the most active with a 50% effective concentration of 0.063 +/- 0.010 MUM in LucNeo#2 cells. The compound did not show apparent cytotoxicity to the host cells at concentrations up to 40 MUM. Western blot analysis demonstrated that HA-719 reduced the levels of NS3 and NS5A proteins in a dose-dependent fashion in the replicon cells. Interestingly, the phenanthridinone derivatives including HA-719 were less potent inhibitors of JFH1 strain (genobtype 2a HCV) in cell-free virus infection assay. Although biochemical assays revealed that HA-719 proved not to inhibit NS3 protease or NS5B RNA polymerase activity at the concentrations capable of inhibiting viral replication, their molecular target (mechanism of inhibition) remains unknown. Considering the fact that most of the anti-HCV agents currently approved or under clinical trials are protease and polymerase inhibitors, the phenanthridinone derivatives are worth pursuing for their mechanism of action and potential as novel anti-HCV agents. PMID- 22085717 TI - Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-SPOP E3 ubiquitin ligase complex. AB - Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis without affecting primary tumorigenesis. The regulatory mechanism of BRMS1 at the protein level has not been revealed until recently. Here, we found that cullin 3 (Cul3), a component of E3 ubiquitin ligase, is a new binding partner of BRMS1 and the interaction between BRMS1 and Cul3 is mediated by the SPOP adaptor protein. Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3-SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells. These results suggest that the novel regulatory mechanism of BRMS1 by Cul3-SPOP complex is important for breast cancer progression. PMID- 22085718 TI - Inhibition of PCGF2 enhances granulocytic differentiation of acute promyelocytic leukemia cell line HL-60 via induction of HOXA7. AB - This study tested the hypothesis that Polycomb Repressive Complex 1 (PRC1) may play a negative role in the granulocytic differentiation of acute promyelocytic leukemia (APL) cells. We first examined the expression of PRC1 genes during all trans retinoic acid (ATRA)-mediated differentiation of human HL-60 cells, and identified PCGF2 as a gene down-regulated by ATRA in a time-dependent manner. Upon gene silencing of PCGF2 with lentiviral short hairpin RNA, granulocytic differentiation was induced as assessed by differentiation marker gene expression, nitroblue tetrazolium staining, Wright-Giemsa staining, and cell cycle analysis. We next identified HOXA7 as a homeobox gene up-regulated by ATRA and successfully induced granulocytic differentiation by overexpression of HOXA7. We next tested the relationship between PCGF2 and HOXA7 by quantifying the changes in HOXA7 and PCGF2 expression upon PCGF2 gene silencing and HOXA7 overexpression, respectively. HOXA7 expression was up-regulated by PCGF2 gene silencing, while PCGF2 expression remained unchanged by ectopic HOXA7 expression, suggesting PCGF2 as acting upstream of HOXA7. Finally, chromatin immunoprecipitation assay was performed with HOXA7 chromatin. We observed gene specific reduction in direct binding of Pcgf2 protein to HOXA7 chromatin upon PCGF2 gene silencing. Taken together, these results support the notion that down regulation of PCGF2 is sufficient to induce granulocytic differentiation of HL-60 cells via de-repression of HOXA7 gene expression. In conclusion, we report that PCGF2, a PRC1 gene, played a negative role in the granulocytic differentiation of human APL cells. PMID- 22085719 TI - Mitogen-activated protein kinase in the amygdala plays a critical role in lithium chloride-induced taste aversion learning. AB - The intracellular mitogen-activated protein kinase (MAPK) pathway in the brain is necessary for the formation of a variety of memories including conditioned taste aversion (CTA) learning. However, the functional role of MAPK activation in the amygdala during lithium chloride (LiCl)-induced CTA learning has not been established. In the present study, we investigated if local microinjection of SL327, a MAPK kinase inhibitor, into the rat amygdala could alleviate LiCl induced CTA learning. Our results revealed that acute administration of a high dose of LiCl (0.15M, 12 ml/kg, i.p.) rapidly increased the level of phosphorylated MAPK (pMAPK)-positive cells in the central nucleus of the amygdala (CeA) and nucleus of the solitary tract (NTS) of rats as measured by immunohistochemistry. Local microinjection of SL327 (1 MUg/0.5 MUl/hemisphere) into the CeA 10 min before LiCl administration decreased both the strength of LiCl-induced CTA paired with 0.125% saccharin and the level of LiCl-induced pMAPK positive cells in the CeA, but not in the NTS. Our data suggest that the intracellular signaling cascade of the MAPK pathway in the CeA plays a critical role in the processing of visceral information induced by LiCl for CTA learning. PMID- 22085720 TI - Different types of exercise induce differential effects on neuronal adaptations and memory performance. AB - Different exercise paradigms show differential effects on various forms of memory. We hypothesize that the differential effects of exercises on memory performance are caused by different neuroplasticity changes in relevant brain regions in response to different exercise trainings. We examined the effects of treadmill running (TR) and wheel running (WR) on the Pavlovian fear conditioning task that assesses learning and memory performance associated with the amygdala (cued conditioning) and both the amygdala and hippocampus (contextual conditioning). The skeletal muscle citrate synthase activity, an indicator of aerobic capacity, was elevated in rats received 4 w of TR, but not WR. While both TR and WR elevated the contextual conditional response, only TR facilitated the cued conditional response. Using a single-neuron labeling technique, we found that while both TR and MR enlarged the dendritic field and increased the spine density in hippocampal CA3 neurons, only TR showed these effects in basolateral amygdalar neurons. Moreover, both types of exercise upregulated synaptic proteins (i.e., TrkB and SNAP-25) in the hippocampus; however only TR showed similar effects in the amygdala. Injection of K252a, a TrkB kinase inhibitor, in the dorsal hippocampus or basolateral amygdala abolished the exercise-facilitated contextual or cued fear learning and memory performance, respectively, regardless of the types of exercise. In summary, our results supported that different types of exercise affect the performance of learning and memory via BDNF-TrkB signaling and neuroplasticity in specific brain regions. The brain region-specific neuronal adaptations are possibly induced by various levels of intensity/stress elicited by different types of exercise. PMID- 22085721 TI - A novel protocol for the production of recombinant LL-37 expressed as a thioredoxin fusion protein. AB - LL-37 is the only cathelicidin-derived antimicrobial peptide found in humans and it has a multifunctional role in host defense. The peptide has been shown to possess immunomodulatory functions in addition to antimicrobial activity. To provide sufficient material for biological and structural characterization of this important peptide, various systems were developed to produce recombinant LL 37 in Escherichia coli. In one previous approach, LL-37 coding sequence was cloned into vector pET-32a, allowing the peptide to be expressed as a thioredoxin fusion. The fusion protein contains two thrombin cleavage sites: a vector-encoded one that is 30-residue upstream of the insert and an engineered one that is immediately adjacent to LL-37. Cleavage at these two sites shall generate three fragments, one of which is the target peptide. However, when the fusion protein was treated with thrombin, cleavage only occurred at the remote upstream site. A plausible explanation is that the thrombin site adjacent to LL-37 is less accessible due to the peptide's aggregation tendency and cleavage at the remote site generates a fragment, which forms a large aggregate that buries the intended site. In this study, I deleted the vector-encoded thrombin site and S tag in pET 32a, and then inserted the coding sequence for LL-37 plus a thrombin site into the modified vector. Although removing the S tag did not change the oligomeric state of the fusion protein, deletion of the vector-encoded thrombin site allowed the fusion to be cleaved at the engineered site to release LL-37. The released peptide was separated from the carrier and cleavage enzyme by size-exclusion chromatography. This new approach enables a quick production of high quality active LL-37 with a decent amount. PMID- 22085722 TI - Production of disulfide-bonded proteins in Escherichia coli. AB - Disulfide bonds are covalent bonds formed post-translationally by the oxidation of a pair of cysteines. A disulfide bond can serve structural, catalytic, and signaling roles. However, there is an inherent problem to the process of disulfide bond formation: mis-pairing of cysteines can cause misfolding, aggregation and ultimately result in low yields during protein production. Recent developments in the understanding of the mechanisms involved in the formation of disulfide bonds have allowed the research community to engineer and develop methods to produce multi-disulfide-bonded proteins to high yields. This review attempts to highlight the mechanisms responsible for disulfide bond formation in Escherichia coli, both in its native periplasmic compartment in wild-type strains and in the genetically modified cytoplasm of engineered strains. The purpose of this review is to familiarize the researcher with the biological principles involved in the formation of disulfide-bonded proteins with the hope of guiding the scientist in choosing the optimum expression system. PMID- 22085723 TI - Regulation of iron transport and the role of transferrin. AB - BACKGROUND: Iron is utilized by several proteins as cofactor for major biological processes. However, iron may also harm cells by catalyzing the generation of free radicals and promoting oxidative stress. Acquisition, transport, utilization and storage of iron are tightly controlled to meet physiological needs and prevent excessive accumulation of the metal within cells. Plasma transferrin has been known for years as a central player in iron metabolism, assigned to circulate iron in a soluble, non-toxic form and deliver it to the erythron and other tissues. Recent data uncovered an additional role of transferrin as an upstream regulator of hepcidin, a liver-derived peptide hormone that controls systemic iron traffic. SCOPE OF REVIEW: Here, we review basic features of iron metabolism, highlighting the function of transferrin in iron transport and cellular iron uptake. We further discuss the role of hepcidin as an orchestrator of systemic iron homeostasis, and the mechanisms underlying hepcidin regulation in response to various physiological cues. Emphasis is given on the role of transferrin on iron-dependent hepcidin regulation. MAJOR CONCLUSIONS: Transferrin exerts a crucial function in the maintenance of systemic iron homeostasis as component of a plasma iron sensing system that modulates hepcidin expression. GENERAL SIGNIFICANCE: Proper expression of transferrin and hepcidin are essential for health, and disruption of their regulatory circuits is associated with iron related disorders. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders. PMID- 22085724 TI - Prevention of mitochondrial disease inheritance by assisted reproductive technologies: prospects and challenges. AB - BACKGROUND: Mitochondrial diseases are caused by the mutations in both nuclear and mitochondrial DNA (mtDNA) and the treatment options for patients who have mitochondrial disease are rather limited. Mitochondrial DNA is transmitted maternally and does not follow a Mendelian pattern of inheritance. Since reliable and predictable detection of mitochondrial disorders in embryos and oocytes is unattainable at present, an alternative approach to this problem has emerged as partial or complete replacement of mutated mtDNA with the wild-type mtDNA through embryo manipulations. Currently available methods to achieve this goal are germinal vesicle transfer (GVT), metaphase chromosome transfer (CT), pronuclear transfer (PNT) and ooplasmic transfer (OT). SCOPE OF REVIEW: We summarize the state of the art regarding these technologies and discuss the implications of recent advances in the field for clinical practice. MAJOR CONCLUSIONS: CT, PNT and GVT techniques hold promise to prevent transmission of mutant mtDNA through ARTs. However, it is clear that mtDNA heteroplasmy in oocytes, embryos and offspring produced by these methods remains as a legitimate concern. GENERAL SIGNIFICANCE: New approaches to eliminate transmission of mutant mtDNA certainly need to be explored in order to bring the promise of clinical application for the treatment of mitochondrial disorders. This article is part of a Special Issue entitled Biochemistry of Mitochondria, Life and Intervention 2010. PMID- 22085725 TI - Is maternal smoking during pregnancy a causal environmental risk factor for adolescent antisocial behavior? Testing etiological theories and assumptions. AB - BACKGROUND: Although many studies indicate that maternal smoking during pregnancy (SDP) is correlated with later offspring antisocial behavior (ASB), recent quasi experimental studies suggest that background familial factors confound the association. The present study sought to test alternative etiological hypotheses using multiple indices of adolescent ASB, comparing differentially exposed siblings, and testing assumptions in the sibling-comparison design. METHOD: The study examined the association between maternal SDP and adolescent-reported ASB, criminal convictions and membership in a group of individuals with early-starting and chronic ASB among 6066 offspring of women from the National Longitudinal Survey of Youth, a representative sample of women in the USA. The analyses controlled for statistical covariates and examined associations while comparing differentially exposed siblings. RESULTS: At the population level, each additional pack of cigarettes per day predicted greater mean adolescent-reported ASB symptoms [ratio of means 1.15, 95% confidence interval (CI) 1.08-1.22], odds of being in the top 10% of ASB [odds ratio (OR) 1.34, 95% CI 1.10-1.65], hazard of a criminal conviction [hazard ratio (HR) 1.51, 95% CI 1.34-1.68] and odds of chronic ASB (OR 1.57, 95% CI 1.25-1.99). SDP robustly predicted most assessments of ASB while controlling for measured covariates. When siblings exposed to differing levels of SDP were compared, however, all of the associations were attenuated and were not statistically significant: adolescent-reported mean ASB (ratio of means 0.86, 95% CI 0.74-1.01), high ASB (OR 0.67, 95% CI 0.41-1.12), criminal conviction (HR 0.98, 95% CI 0.66-1.44) and chronic ASB (OR 0.80, 95% CI 0.46-1.38). CONCLUSIONS: The results strongly suggest that familial factors account for the correlation between SDP and offspring adolescent ASB, rather than a putative causal environmental influence of SDP. PMID- 22085727 TI - Biomechanical evaluation of a novel reverse coracoacromial ligament reconstruction for acromioclavicular joint separation. AB - BACKGROUND: Enhancing anterior-posterior (AP) stability in acromioclavicular (AC) reconstruction may be advantageous. PURPOSE: To compare the initial stability of AC reconstructions with and without augmentation by either (1) a novel "reverse" coracoacromial (CA) ligament transfer or (2) an intramedullary AC tendon graft. HYPOTHESIS: Reverse CA transfer will improve AP stability compared with isolated coracoclavicular (CC) reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Six matched pairs of cadaveric shoulders underwent distal clavicle resection and CC reconstruction. Displacement (mm) was measured during cyclic loading along AP (+/-25 N) and superior-inferior (SI; 10-N compression, 70-N tension) axes. Pairs were randomized to receive each augmentation and the same loading protocol applied. RESULTS: Reverse CA transfer (3.71 +/- 1.3 mm, standard error of the mean [SEM]; P = .03) and intramedullary graft (3.41 +/- 1.1 mm; P = .03) decreased AP translation compared with CC reconstruction alone. The SI displacement did not differ. Equivalence tests suggest no difference between augmentations in AP or SI restraint. CONCLUSION: Addition of either reverse CA transfer or intramedullary graft demonstrates improved AP restraint and provides similar SI stability compared with isolated CC reconstruction. CLINICAL RELEVANCE: Reverse CA ligament transfer may be a reasonable alternative to a free tendon graft to augment AP restraint in AC reconstruction. PMID- 22085726 TI - Sequentially acting Sox transcription factors in neural lineage development. AB - Pluripotent embryonic stem (ES) cells can generate all cell types, but how cell lineages are initially specified and maintained during development remains largely unknown. Different classes of Sox transcription factors are expressed during neurogenesis and have been assigned important roles from early lineage specification to neuronal differentiation. Here we characterize the genome-wide binding for Sox2, Sox3, and Sox11, which have vital functions in ES cells, neural precursor cells (NPCs), and maturing neurons, respectively. The data demonstrate that Sox factor binding depends on developmental stage-specific constraints and reveal a remarkable sequential binding of Sox proteins to a common set of neural genes. Interestingly, in ES cells, Sox2 preselects for neural lineage-specific genes destined to be bound and activated by Sox3 in NPCs. In NPCs, Sox3 binds genes that are later bound and activated by Sox11 in differentiating neurons. Genes prebound by Sox proteins are associated with a bivalent chromatin signature, which is resolved into a permissive monovalent state upon binding of activating Sox factors. These data indicate that a single key transcription factor family acts sequentially to coordinate neural gene expression from the early lineage specification in pluripotent cells to later stages of neuronal development. PMID- 22085728 TI - A cost-effectiveness analysis comparing 3 anterior cruciate ligament graft types: bone-patellar tendon-bone autograft, hamstring autograft, and allograft. AB - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction, despite being one of the most common surgical interventions, is also one of the least agreed upon surgeries when it comes to optimum graft choice. Three graft choices stand among the most widely used in this procedure: (1) bone-patellar tendon-bone autograft (BPTB), (2) quadruple hamstring tendon autograft (HS), and (3) allograft. HYPOTHESIS: Bone-patellar tendon-bone ACL reconstruction is the most cost effective method of ACL reconstruction. STUDY DESIGN: Economic and decision analysis; Level of evidence, 2. METHODS: A simplified decision tree model was created with theoretical patients assigned equally to 1 of 3 ACL reconstruction cohorts based on graft type. These treatment arms were further divided into outcome arms based on probabilities from the literature. The terminal outcomes were assigned a health state/utility score and a societal cost. Utilities were calculated from real clinic patients via the time trade-off questionnaire. Costs were literature based. An incremental cost-effectiveness ratio of $50 000/quality adjusted life year (QALY) was used as the threshold for cost-effectiveness. RESULTS: Hamstring tendon autograft was the least costly ($5375/surgery) and most effective (0.912) graft choice, dominating both BPTB and allograft reconstructions. Allograft was both the most costly and least effective strategy for the average patient undergoing ACL reconstruction. However, if baseline costs of BPTB could be reduced (by $500) or the effectiveness increased (anterior knee pain <15% or postoperative instability <7%), then BPTB became an incrementally cost-effective choice. In addition, if the effectiveness of HS could be reduced (instability >29% or revision rates >7%), then BPTB also became incrementally cost-effective. CONCLUSIONS: This model suggests that hamstring autograft ACL reconstruction is the most cost-effective method of surgery for the average patient with ACL deficiency. However, specific clinical scenarios that change postoperative probabilities of the different complications may sway surgeons to choose either allografts or BPTB. Cost-effectiveness analysis is not intended to replace individual clinician judgment but rather is intended to examine both the effectiveness and costs associated with theoretical groups undergoing specific multifactorial decisions. PMID- 22085729 TI - Prospective randomized clinical evaluation of conventional single-bundle, anatomic single-bundle, and anatomic double-bundle anterior cruciate ligament reconstruction: 281 cases with 3- to 5-year follow-up. AB - BACKGROUND: Three different techniques of anterior cruciate ligament (ACL) reconstruction--conventional (transtibial) single bundle (CSB), anatomic single bundle (ASB), and anatomic double bundle (ADB)--have been described. PURPOSE: To determine if double-bundle reconstruction is needed to restore rotational stability or if anatomic placement of a single bundle can yield similar results. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: From December 2005 to December 2007, 320 patients were prospectively randomized into 3 groups: ADB, ASB, and CSB reconstruction. The average follow-up was 51.15 months (range, 39-63 months). At the final follow-up, 281 patients were available. In all groups, hamstring tendons were used with suspensory fixation on the femoral side and bioabsorbable interference screw fixation on the tibial side. The outcomes were evaluated by an independent blinded observer using the Lysholm score and subjective International Knee Documentation Committee (IKDC) form. The KT-1000 arthrometer was used to evaluate anteroposterior stability, and the pivot shift test was used to determine rotational stability. RESULTS: Anatomic single bundle reconstruction resulted in better anteroposterior and rotational stability than CSB reconstruction (average side-to-side difference for anterior tibial translation was 1.6 mm in the ASB group vs 2.0 mm in the CSB group; P = .002). Negative pivot shift was 66.7% vs 41.7% (P = .003). In other parameters, the differences between groups were not statistically significant. The results of the ADB group were also superior to the ASB group for anteroposterior and rotational stability (average side-to-side difference for anterior tibial translation was 1.2 mm in the ADB group vs 1.6 mm in the ASB group; P = .002). Negative pivot shift was 93.1% vs 66.7%, respectively (P < .001), and range of motion was also significantly different (P = .005). The Lysholm score was 90.9, 91.8, and 93.0 in the CSB, ASB, and ADB groups, respectively. The difference was significant only when we compared ADB and CSB (P = .025). Subjective IKDC scores were 90.2, 90.6, and 92.1 in the CSB, ASB, and ADB groups, respectively. The difference was not significant. CONCLUSION: Anatomic double-bundle ACL reconstruction is significantly superior to conventional single-bundle ACL reconstruction and better than anatomic single-bundle reconstruction. Anatomic single-bundle reconstruction was superior to conventional single-bundle reconstruction. However, these differences are small and may not be clinically relevant. PMID- 22085730 TI - Advancing regenerative surgery in orthopaedic sports medicine: the critical role of the surgeon. AB - The constant desire to improve outcomes in orthopaedic sports medicine requires us to continuously consider the challenges faced in the surgical repair or reconstruction of soft tissue and cartilaginous injury. In many cases, surgical efforts targeted at restoring normal anatomy and functional status are ultimately impaired by the biological aspect of the natural history of these injuries, which acts as an obstacle to a satisfactory repair process after surgery. The clinical management of sports injuries and the delivery of appropriate surgical intervention are continuously evolving, and it is likely that the principles of regenerative medicine will have an increasing effect in this specialized field of orthopaedic practice going forward. Ongoing advances in arthroscopy and related surgical techniques should facilitate this process. In contrast to the concept of engineered replacement of entire tissues, it is probable that the earliest effect of regenerative strategies seen in clinical practice will involve biological augmentation of current operative techniques via a synergistic process that might be best considered "regenerative surgery." This article provides an overview of the principles of regenerative surgery in cartilage repair and related areas of orthopaedic surgery sports medicine. The possibilities and challenges of a gradual yet potential paradigm shift in treatment through the increased use of biological augmentation are considered. The translational process and critical role to be played by the specialist surgeon are also addressed. We conclude that increased understanding of the potential and challenges of regenerative surgery should allow those specializing in orthopaedic surgery sports medicine to lead the way in advancing the frontiers of biological strategies to enhance modern clinical care in an evidence-based manner. PMID- 22085731 TI - Force measurements in the medial meniscus posterior horn attachment: effects of anterior cruciate ligament removal. AB - BACKGROUND: Tears of the medial meniscus posterior horn attachment (PHA) occur clinically, and an anterior cruciate ligament (ACL)-deficient knee may be more vulnerable to this injury. HYPOTHESIS: The PHA forces from applied knee loadings will increase after removal of the ACL. STUDY DESIGN: Controlled laboratory study. METHODS: A cap of bone containing the medial meniscus PHA was attached to a load cell that measured PHA tensile force. Posterior horn attachment forces were recorded before and after ACL removal during anteroposterior (AP) laxity testing at +/-200 N and during passive knee extension tests with 5 N.m tibial torque and varus-valgus moment. Selected tests were also performed with 500 N joint load. RESULTS: For AP tests with no joint load, ACL removal increased laxity between 0 degrees and 90 degrees and increased PHA force generated by applied anterior tibial force between 30 degrees and 90 degrees . For AP tests with an intact ACL, application of joint load approximately doubled PHA forces. Anteroposterior testing of ACL-deficient knees was not possible with joint load because of bone cap failures from high PHA forces. Removal of the ACL during knee extension tests under joint load significantly increased PHA forces between 20 degrees and 90 degrees of flexion. For unloaded tests with applied tibial torque and varus-valgus moment, ACL removal had no significant effect on PHA forces. CONCLUSION: Applied anterior tibial force and external tibial torque were loading modes that produced relatively high PHA forces, presumably by impingement of the medial femoral condyle against the medial meniscus posterior horn rim. Under joint load, an ACL-deficient knee was particularly susceptible to PHA injury from applied anterior tibial force. CLINICAL RELEVANCE: Because tensile forces developed in the PHA are also borne by meniscus tissue near the attachment site, loading mechanisms that produce high PHA forces could also produce complete or partial radial tears near the posterior horn, a relatively common clinical observation. PMID- 22085732 TI - Duration of antibiotic therapy for bacteremia: a systematic review and meta analysis. AB - INTRODUCTION: The optimal duration of antibiotic therapy for bloodstream infections is unknown. Shorter durations of therapy have been demonstrated to be as effective as longer durations for many common infections; similar findings in bacteremia could enable hospitals to reduce antibiotic utilization, adverse events, resistance and costs. METHODS: A search of the MEDLINE, EMBASE and COCHRANE databases was conducted for the years 1947-2010. Controlled trials were identified that randomized patients to shorter versus longer durations of treatment for bacteremia, or the infectious foci most commonly causing bacteremia in critically ill patients (catheter-related bloodstream infections (CRBSI), intra-abdominal infections, pneumonia, pyelonephritis and skin and soft-tissue infections (SSTI)). RESULTS: Twenty-four eligible trials were identified, including one trial focusing exclusively on bacteremia, zero in catheter related bloodstream infection, three in intra-abdominal infection, six in pyelonephritis, thirteen in pneumonia and one in skin and soft tissue infection. Thirteen studies reported on 227 patients with bacteremia allocated to 'shorter' or 'longer' durations of treatment. Outcome data were available for 155 bacteremic patients: neonatal bacteremia (n = 66); intra-abdominal infection (40); pyelonephritis (9); and pneumonia (40). Among bacteremic patients receiving shorter (5-7 days) versus longer (7-21 days) antibiotic therapy, no significant difference was detected with respect to rates of clinical cure (45/52 versus 47/49, risk ratio 0.88, 95% confidence interval [CI] 0.77-1.01), microbiologic cure (28/28 versus 30/32, risk ratio 1.05, 95% CI 0.91-1.21), and survival (15/17 versus 26/29, risk ratio 0.97, 95% CI 0.76-1.23). CONCLUSIONS: No significant differences in clinical cure, microbiologic cure and survival were detected among bacteremic patients receiving shorter versus longer duration antibiotic therapy. An adequately powered randomized trial of bacteremic patients is needed to confirm these findings. PMID- 22085733 TI - Inductive specification and axonal orientation of spinal neurons mediated by divergent bone morphogenetic protein signaling pathways. AB - BACKGROUND: Bone morphogenetic protein (BMP)7 evokes both inductive and axon orienting responses in dorsal interneurons (dI neurons) in the developing spinal cord. These events occur sequentially during the development of spinal neurons but in these and other cell types such inductive and acute chemotactic responses occur concurrently, highlighting the requirement for divergent intracellular signaling. Both type I and type II BMP receptor subtypes have been implicated selectively in orienting responses but it remains unclear how, in a given cell, divergence occurs. We have examined the mechanisms by which disparate BMP7 activities are generated in dorsal spinal neurons. RESULTS: We show that widely different threshold concentrations of BMP7 are required to elicit the divergent inductive and axon orienting responses. Type I BMP receptor kinase activity is required for activation of pSmad signaling and induction of dI character by BMP7, a high threshold response. In contrast, neither type I BMP receptor kinase activity nor Smad1/5/8 phosphorylation is involved in the low threshold orienting responses of dI axons to BMP7. Instead, BMP7-evoked axonal repulsion and growth cone collapse are dependent on phosphoinositide-3-kinase (PI3K) activation, plausibly through type II receptor signaling. BMP7 stimulates PI3K-dependent signaling in dI neurons. BMP6, which evokes neural induction but does not have orienting activity, activates Smad signaling but does not stimulate PI3K. CONCLUSIONS: Divergent signaling through pSmad-dependent and PI3K-dependent (Smad independent) mechanisms mediates the inductive and orienting responses of dI neurons to BMP7. A model is proposed whereby selective engagement of BMP receptor subunits underlies choice of signaling pathway. PMID- 22085734 TI - Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration. AB - BACKGROUND: The molecular mechanisms governing vertebrate appendage regeneration remain poorly understood. Uncovering these mechanisms may lead to novel therapies aimed at alleviating human disfigurement and visible loss of function following injury. Here, we explore tadpole tail regeneration in Xenopus tropicalis, a diploid frog with a sequenced genome. RESULTS: We found that, like the traditionally used Xenopus laevis, the Xenopus tropicalis tadpole has the capacity to regenerate its tail following amputation, including its spinal cord, muscle, and major blood vessels. We examined gene expression using the Xenopus tropicalis Affymetrix genome array during three phases of regeneration, uncovering more than 1,000 genes that are significantly modulated during tail regeneration. Target validation, using RT-qPCR followed by gene ontology (GO) analysis, revealed a dynamic regulation of genes involved in the inflammatory response, intracellular metabolism, and energy regulation. Meta-analyses of the array data and validation by RT-qPCR and in situ hybridization uncovered a subset of genes upregulated during the early and intermediate phases of regeneration that are involved in the generation of NADP/H, suggesting that these pathways may be important for proper tail regeneration. CONCLUSIONS: The Xenopus tropicalis tadpole is a powerful model to elucidate the genetic mechanisms of vertebrate appendage regeneration. We have produced a novel and substantial microarray data set examining gene expression during vertebrate appendage regeneration. PMID- 22085735 TI - Nurse managers' experience with ethical issues in six government hospitals in Malaysia: a cross-sectional study. AB - BACKGROUND: Nurse managers have the burden of experiencing frequent ethical issues related to both their managerial and nursing care duties, according to previous international studies. However, no such study was published in Malaysia. The purpose of this study was to explore nurse managers' experience with ethical issues in six government hospitals in Malaysia including learning about the way they dealt with the issues. METHODS: A cross-sectional study was conducted in August-September, 2010 involving 417 (69.2%) of total 603 nurse managers in the six Malaysian government hospitals. Data were collected using three-part self administered questionnaire. Part I was regarding participants' demographics. Part II was about the frequency and areas of management where ethical issues were experienced, and scoring of the importance of 11 pre-identified ethical issues. Part III asked how they dealt with ethical issues in general; ways to deal with the 11 pre-identified ethical issues, and perceived stress level. Data were analyzed using descriptive statistics, cross-tabulations and Pearson's Chi square. RESULTS: A total of 397 (95.2%) participants experienced ethical issues and 47.2% experienced them on weekly to daily basis. Experiencing ethical issues were not associated with areas of practice. Top area of management where ethical issues were encountered was "staff management", but "patient care" related ethical issues were rated as most important. Majority would "discuss with other nurses" in dealing generally with the issues. For pre-identified ethical issues regarding "patient care", "discuss with doctors" was preferred. Only 18.1% referred issues to "ethics committees" and 53.0% to the code of ethics. CONCLUSIONS: Nurse managers, regardless of their areas of practice, frequently experienced ethical issues. For dealing with these, team-approach needs to be emphasized. Proper understanding of the code of ethics is needed to provide basis for reasoning. PMID- 22085737 TI - Environ centrality reveals the tendency of indirect effects to homogenize the functional importance of species in ecosystems. AB - Ecologists and conservation biologists need to identify the relative importance of species to make sound management decisions and effectively allocate scarce resources. We introduce a new method, termed environ centrality, to determine the relative importance of a species in an ecosystem network with respect to ecosystem energy-matter exchange. We demonstrate the uniqueness of environ centrality by comparing it to other common centrality metrics and then show its ecological significance. Specifically, we tested two hypotheses on a set of 50 empirically based ecosystem network models. The first concerned the distribution of centrality in the community. We hypothesized that the functional importance of species would tend to be concentrated into a few dominant species followed by a group of species with lower, more even importance as is often seen in dominance diversity curves. Second, we tested the systems ecology hypothesis that indirect relationships homogenize the functional importance of species in ecosystems. Our results support both hypotheses and highlight the importance of detritus and nutrient recyclers such as fungi and bacteria in generating the energy-matter flow in ecosystems. Our homogenization results suggest that indirect effects are important in part because they tend to even the importance of species in ecosystems. A core contribution of this work is that it creates a formal, mathematical method to quantify the importance species play in generating ecosystem activity by integrating direct, indirect, and boundary effects in ecological systems. PMID- 22085736 TI - Biophysical connection between evolutionary dynamics and thermodynamics in in vitro evolution. AB - We analyzed a mathematical model of in vitro evolution conducted by repetition of mutagenesis and selection processes. The selection process consists of the selective enrichment and subsequent sampling as follows: each mutant with fitness W is amplified by the Boltzmann factor exp(rW/k(B)T(the)), where the fitness W is defined as the negative Gibbs free energy (-DeltaG) in a reaction of the phenotypic molecules and r is the round number of the selective enrichment; then, an arbitrary mutant is randomly chosen from the resulting mutant population and it becomes a new parent in the next generation. As a result, we found that the evolutionary dynamics is described in a mathematical framework similar to thermodynamics: the "evolution constant" k(E) and "evolutionary temperature" T(evo) play key roles similar to the Boltzmann constant k(B) and thermodynamic temperature T(the), respectively. In the stationary state of the evolutionary dynamics, the attractor of the fitness is in inverse proportion to k(E)T(evo). Furthermore, beyond the mathematical analogy, we obtained a biophysical connection between evolutionary dynamics and thermodynamics. Particularly, we found that T(evo) and T(the) are connected by k(E)T(evo)~k(B)T(the)/2r. These results suggest that we can predict the fitness value in the stationary state by the thermodynamic temperature T(the) in the experimental setup. PMID- 22085738 TI - On the meaning and estimation of plasmid transfer rates for surface-associated and well-mixed bacterial populations. AB - Conjugative plasmid transfer is key to the ability of bacteria to rapidly adapt to new environments, but there is no agreement on a single quantitative measure of the rate of plasmid transfer. Some studies derive estimates of transfer rates from mass-action differential equation models of plasmid population biology. The often-used 'endpoint method' is such an example. Others report measures of plasmid transfer efficiency that simply represent ratios of plasmid-bearing and plasmid-free cell densities and do not correspond to parameters in any mathematical model. Unfortunately, these quantities do not measure the same thing - sometimes differing by orders of magnitude - and their use is often clouded by a lack of specificity. Moreover, they do not distinguish between bulk transfer rates that are only relevant in well-mixed populations and the 'intrinsic' rates between individual cells. This leads to problems for surface-associated populations, which are not well-mixed but spatially structured. We used simulations of a spatially explicit mathematical model to evaluate the effectiveness of these various plasmid transfer efficiency measures when they are applied to surface-associated populations. The simulation results, supported by some experimental findings, showed that these measures can be affected by initial cell densities, donor-to-recipient ratios and initial cell cluster size, and are therefore flawed as universal measures of plasmid transfer efficiency. The simulations also allowed us to formulate some guiding principles on when these estimates are appropriate for spatially structured populations and how to interpret the results. While we focus on plasmid transfer, the general lessons of this study should apply to any measures of horizontal spread (e.g., infection rates in epidemiology) that are based on simple mass-action models (e.g., SIR models in epidemiology) but applied to spatial settings. PMID- 22085739 TI - Mathematical modeling of transport and degradation of feedstuffs in the small intestine. AB - We describe a mathematical model of digestion in the small intestine. The main interest of our work is to consider simultaneously the different aspects of digestion i.e. transport of the bolus all along the intestine, feedstuffs degradation according to the enzymes and local physical conditions, and nutrients absorption. A system of coupled ordinary differential equations is used to model these phenomena. The major unknowns of this system are the position of the bolus and its composition. This system of equations is solved numerically. We present several numerical computations for the degradation, absorption and transport of the bolus with acceptable accuracy regarding the overall behavior of the model and also when challenged versus experimental data. The main feature and interest of this model are its genericity. Even if we are at an early stage of development, our approach can be adapted to deal with contrasted feedstuffs in non-ruminant animal to predict the composition and velocity of bolus in the small intestine. PMID- 22085740 TI - Ringer's lactate improves liver recovery in a murine model of acetaminophen toxicity. AB - BACKGROUND: Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Liver regeneration is a vital process for survival after a toxic insult. Since hepatocytes are mostly in a quiescent state (G0), the regeneration process requires the priming of hepatocytes by cytokines such as TNF-alpha and IL-6. Ringer's lactate solution (RLS) has been shown to increase serum TNF-alpha and IL 6 in patients and experimental animals; in addition, RLS also provides lactate, which can be used as an alternative metabolic fuel to meet the higher energy demand by liver regeneration. Therefore, we tested whether RLS therapy improves liver recovery after APAP overdose. METHODS: C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (300 mg/kg dissolved in 1 mL sterile saline). Following 2 hrs of APAP challenge, the mice were given 1 mL RLS or Saline treatment every 12 hours for a total of 72 hours. RESULTS: 72 hrs after APAP challenge, compared to saline-treated group, RLS treatment significantly lowered serum transaminases (ALT/AST) and improved liver recovery seen in histopathology. This beneficial effect was associated with increased hepatic tissue TNF-alpha concentration, enhanced hepatic NF-kappaB DNA binding and increased expression of cell cycle protein cyclin D1, three important factors in liver regeneration. CONCLUSION: RLS improves liver recovery from APAP hepatotoxicity. PMID- 22085741 TI - Longitudinal study of vitamins A, E and lipid oxidative damage in human milk throughout lactation. AB - BACKGROUND: Little is known about the intensity of oxidative damage in human milk resulting from maternal oxidative stress. The aim of our study was to explore the changes in Total Antioxidant Status (TAS) and concentrations of antioxidative vitamins and isoprostanes (markers of oxidative stress) in human colostrum and mature milk. METHODS: The study included 49 postpartum women with normal, spontaneous full term delivery. The exclusion criteria included active and passive smoking, acute and chronic disorders, and pharmacotherapy other than vitamin supplementation. Colostrum samples were collected on the 3rd day after delivery and breast milk samples between the 30th and the 32nd day after delivery. TAS of colostrum/breast milk was determined by Rice-Evans and Miller method. The amount of vitamins A and E was measured by HPLC. Isoprostane concentrations in colostrum/mature milk and urine were determined immunoenzymatically. RESULTS: No significant differences were observed in maternal dietary intakes of vitamins A and E determined prior to the colostrum and mature milk sampling. The TAS of mature milk was significantly higher compared to colostrum (P=0.002), while vitamin A and E concentrations were significantly lower (P=0.003 and P=0.001). Although the isoprostane concentration of mature milk was significantly higher than the colostrum concentration, this difference was not significant (P=0.129). CONCLUSION: Human milk is a source of antioxidative vitamins and their concentrations decrease throughout the lactation, while their total antioxidative properties increase. The phase of lactation does not affect the degree of human milk's lipid oxidative damage. PMID- 22085742 TI - The D2/D3-receptor antagonist tiapride impairs concurrent but not sequential taste aversion learning. AB - Taste aversion learning (TAL) is a learning modality in which the animals reject a gustatory stimulus associated with the administration of noxious visceral substances. This learning can be established by concurrent or sequential procedures that involve different anatomical and functional mechanisms and may constitute distinct learning modalities. The dopaminergic system has been related to various learning processes and goal-directed behaviours. The present study examined the effect of the administration of tiapride, a D(2)/D(3) dopaminergic antagonist, on concurrent and sequential TAL. Results obtained showed that pre treatment with tiapride blocks the acquisition of concurrent TAL but does not affect sequential TAL, including reversal learning tasks. These results demonstrate the involvement of the D(2)/D(3) dopaminergic receptors in the former but not the latter learning process. The dopaminergic system appears to participate in concurrent TAL, an "implicit" learning modality, but not in sequential TAL, which is considered a relational/explicit acquisition process. PMID- 22085743 TI - Cypermethrin induced damage in genomic DNA and histopathological changes in brain and haematotoxicity in rats: the protective effect of sesame oil. AB - The protective effect of sesame oil against cypermethrin-induced brain toxicity was studied. Female rats were orally treated with cypermethrin, sesame oil and their combination for 30 consecutive days. The results showed that cypermethrin increased thiobarbituric acid-reactive substances (TBARS), and decreased glutathione (GSH) and the activities of the antioxidant enzymes. Brain injury was confirmed by histopathological changes and DNA damage. Also, the reduction in the activities of acetylcholinesterase and monoamine oxidase (AChE & MAO), total protein, albumin and body weight, and the induction in triacylglycerol and cholesterol have been observed due to cypermethrin toxicity. Animals treated with sesame oil and cypermethrin together showed that brain TBARS and plasma triacylglycerol and cholesterol returned to the control level which indicating a protective effect of sesame oil. Also, sesame oil was able to attenuate the decrease in total protein, albumin, triacylglycerol and cholesterol, GSH, AChE and antioxidant enzymes induced by cypermethrin. In addition, sesame oil protected the brain histological changes and fragmentation of genomic DNA in animals treated with cypermethrin. The present results showed a protective effect of sesame oil against the cypermethrin induced brain toxicity and this could be associated mainly with the attenuation of the oxidative stress and the preservation in antioxidant enzymes. PMID- 22085744 TI - Five choice serial reaction time performance in the HdhQ92 mouse model of Huntington's disease. AB - Huntington's disease is an autosomal dominant genetic disorder, with motor, cognitive and psychiatric symptoms. To date there is no cure. In order to understand better this disease and to develop novel treatments, many genetically modified animal models of Huntington's disease have been created. However, to utilize these models fully, appropriate functional assays need to be developed for behavioural assessments of the mice. Various facets of attention have been reported to be affected in Huntington's disease patients, and the Hdh(Q92/Q92) mice have been shown to have deficits on operant tasks which have attentional components. In the present study, the Hdh(Q92/Q92) mouse model is assessed on a well established test of attentional function, the operant 5-choice serial reaction time task (5-CSRT), in which the mice must respond with a nose poke to light stimuli presented randomly across a 5 hole light array to receive a reward. In the present paper, the Hdh(Q92/Q92) mice exhibited deficits on the 5-CSRT when pseudorandomly presented with stimuli of different durations. However, alterations in the pacing of the task, therefore requiring an increase in sustained attention, did not affect the Hdh(Q92/Q92) mice more than their wildtype littermates. This study indicates that the Hdh(Q92/Q92) mice may have deficits in aspects of attentional function, in particular disruption in the ability to maintain attention in the visuospatial domain, suggesting that this knock-in mouse model of Huntington's disease may be a relevant model of the disease for the testing of novel therapeutic interventions. PMID- 22085745 TI - From the editor. PMID- 22085746 TI - Filaments assembly of ectopically expressed Caenorhabditis elegans lamin within Xenopus oocytes. AB - Lamins are the major components of the nuclear lamina, a filamentous layer underlying the inner nuclear membrane and attached to the peripheral chromatin. Lamins are required for maintaining nuclear shape and are involved in most nuclear activities. Here, we studied the 3D organization of the nuclear lamina formed upon the expression of Caenorhabditis elegans lamin (Ce-lamin) within the nucleus of a Xenopus laevis oocyte. We show that Ce-lamin forms an intricate 3D meshwork of 5-6 nm lamin protofilaments. The diverse protofilament interactions and organization may shed light upon the unique mechano-elastic properties of the nuclear lamina scaffold supporting the nuclear envelope. The Q159K Hutchinson Gilford Progeria Syndrome-linked mutation alters interactions between protofilaments within the lamina, leading to the formation of more bundled arrays of less isotropically-oriented protofilaments. Using this system, we show for the first time the organization of lamin proteins that were translated and assembled within the environment of a living cell. PMID- 22085747 TI - Reconstructing adhesion structures in tissues by cryo-electron tomography of vitrified frozen sections. AB - Cryo-electron tomography enables three-dimensional insights into the macromolecular architecture of cells in a close-to-life state. However, it is limited to thin specimens, <1.0 MUm in thickness, typically restricted to the peripheral areas of intact eukaryotic cells. Analysis of tissue ultrastructure, on the other hand, requires physical sectioning approaches, preferably cryo sectioning, following which electron tomography (ET) may be performed. Nevertheless, cryo-electron microscopy of vitrified sections is a demanding technique and typically cannot be used to examine thick sections, >80-100 nm, due to surface crevasses. Here, we explore the potential use of cryo-ET of vitrified frozen sections (VFSs) for imaging cell adhesions in chicken smooth muscle and mouse epithelial tissues. By investigating 300-400 nm thick sections, which are collected on the EM grid and re-vitrified, we resolved fine 3D structural details of the membrane-associated dense plaques and flanking caveoli in smooth muscle tissue, and desmosomal adhesions in stratified epithelium. Technically, this method offers a simple approach for reconstructing thick volumes of hydrated frozen sections. PMID- 22085748 TI - Crystallographic and spectroscopic characterizations of Sulfolobus solfataricus TrxA1 provide insights into the determinants of thioredoxin fold stability. AB - Structural characterizations of thioredoxins (Trxs) are important for their involvement in severe pathologies and for their stable scaffold. Here we report a combined structural and spectroscopic characterization of a Trx isolated from the hyperthermophilic archaeon Sulfolobus solfataricus (SsTrxA1). Thermal denaturation unveils that SsTrxA1 is endowed with a remarkable stability in the explored temperature range 50-105 degrees C. The structure of the oxidized form of SsTrxA1 determined at 1.9A resolution presents a number of peculiar features. Although the protein was crystallized in a slightly acid medium (pH 6.5) as many as ten intramolecular/intermolecular carboxyl-carboxylate interactions involving glutamic and aspartic acid side chains are found in three independent SsTrxA1 molecules present in the asymmetric unit. Surprisingly for a hyperthermostable protein, the structure of SsTrxA1 is characterized by the presence (a) of a very limited number of intramolecular salt bridges and (b) of a cavity nearby Cys52, a residue that is frequently a phenylananine in other members of the family. Chemical denaturation investigations carried out on SsTrxA1 and SsTrxA2 show that both proteins present a significant stability against guanidine hydrochloride, thus indicating that ionic interactions play a minor role in their stabilization. Compared to Trxs from mesophilic sources, SsTrxA1 displays a longer alpha-helix 1 and a shorter loop connecting this alpha-helix with beta-strand 2. As these features are shared with Trxs isolated from thermophilic sources, the shortening of this loop may be a general strategy adopted to stabilize this fold. This feature may be exploited for the design of hyperthermostable Trx scaffolds. PMID- 22085749 TI - Helical arrangement of filaments in microvillar actin bundles. AB - Actin filament arrays in in vivo microvillar bundles of rat intestinal enterocyte were re-evaluated using electron tomography (ET). Conventional electron microscope observation of semi-thin cross sections (300nm thick) of high-pressure freeze fixed and resin embedded brush border has shown a whirling pattern in the center of the microvilli instead of hexagonally arranged dots, which strongly suggests that the bundle consists of a non-parallel array of filaments. A depth compensation method for the ET was developed to estimate the actual structure of the actin bundle. Specimen shrinkage by beam irradiation during image acquisition was estimated to be 63%, and we restored the original thickness in the reconstruction. The depth compensated tomogram displayed the individual actin filaments within the bundles and it indicated that the actin filaments do not lie exactly parallel to each other: instead, they are twisted in a clockwise coil with a pitch of ~120 degrees /MUm. Furthermore, the lattice of actin filaments was occasionally re-arranged within the bundle. As the microvillar bundle mechanically interacts with the membrane and is thought to be compressed by the membrane's faint tensile force, we removed the shrouding membrane using detergents to eliminate the mechanical interaction. The bared bundles no longer showed the whirling pattern, suggesting that the bundle had released its coiled property. These findings indicate that the bundle has not rigid but elastic properties and a dynamic transformation in its structure caused by a change in the mechanical interaction between the membrane and the bundle. PMID- 22085751 TI - Antinociception of beta-D-glucan from Pleurotus pulmonarius is possibly related to protein kinase C inhibition. AB - beta-D-Glucan, a polysaccharide isolated from an edible mushroom Pleurotus pulmonarius (Fr.) Quel., presented antinociceptive activity in mice. This study evaluated the involvement of transient receptor potential (TRP) channels and protein kinase C (PKC) on antinociceptive effect of a (1->3),(1->6)-linked beta-D glucan (GL) in mice. Intraperitoneal administration of GL potently inhibited nociceptive responses induced by intraplantar injections of capsaicin, cinnamaldehyde, menthol, acidified saline and phorbol myristate acetate (PMA). Moreover, Western blot analysis revealed that GL treatment also prevented PMA induced PKCE activation. Collectively, present results demonstrate that GL could constitute an attractive molecule of interest for the development of new analgesic drugs. PMID- 22085750 TI - The hyperimmunoglobulin E syndrome--clinical manifestation diversity in primary immune deficiency. AB - The hyper-IgE syndromes are rare, complex primary immunodeficiencies characterized by clinical manifestation diversity, by particular susceptibility to staphylococcal and mycotic infections as well as by a heterogeneous genetic origin. Two distinct entities--the classical hyper-IgE syndrome which is inherited in an autosomal dominant pattern and the autosomal recessive hyper-IgE syndrome--have been recognized. The autosomal dominant hyper-IgE syndrome is associated with a cluster of facial, dental, skeletal, and connective tissue abnormalities which are not observable in the recessive type. In the majority of affected patients with autosomal dominant hyper-IgE syndrome a mutation in the signal transducer and the activator of the transcription 3 gene has been identified, leading to an impaired Th17 cells differentiation and to a downregulation of an antimicrobial response. A mutation in the dedicator of the cytokinesis 8 gene has been identified as the cause of many cases with autosomal recessive hyper-IgE syndrome and, in one patient, a mutation in tyrosine kinase 2 gene has been demonstrated. In this paper, the authors provide a review of the clinical manifestations in the hyper-IgE syndromes with particular emphasis on the diversity of their phenotypic expression and present current diagnostic guidelines for these diseases. PMID- 22085752 TI - Presence of alternating glucosaminoglucan in the sheath of Thiothrix nivea. AB - A sheath-forming sulfa oxidizer, Thiothrix nivea, was mixotrophically cultured in a medium supplemented with acetic acid and sodium disulfide. Its sheath, a microtube-like extracellular supermolecule, was prepared by selectively removing the cells with lysozyme, sodium dodecyl sulfate, and sodium hydroxide. The sheath was not visibly affected by hydrazine treatment, suggesting that it is not a proteinous supermolecule. From the acid hydrolysate of the sheath, glucose and glucosamine were detected in an approximate molar ratio of 1:1. Three other saccharic compounds were detected and recovered by HPLC as fluorescent derivatives prepared by reaction with 4-aminobenzoic acid ethyl ester. Nuclear magnetic resonance (NMR) analysis suggested that one of the derivatives was derived from an unidentified deoxypentose. NMR analysis for the other 2 derivatives showed that they were derived from beta-1,4-linked disaccharides and tetrasaccharides, which were composed of glucose and glucosamine. The sheath was readily broken down by weak HCl treatment, releasing an unidentified deoxypentose and polymer. Chemical analysis showed the presence of beta-1,4-linked D-Glcp and D-GlcNp in the polymer. NMR analysis revealed that the polymer had a repeating unit of ->4)-D-Glcp-(beta1->4)-D-GlcNp-(beta1->. The solid-state 1D-(13)C NMR spectrum of the polymer in N-acetylated form supported this result. The molecular weight of the polymer was estimated to be 8.2*10(4) by size exclusion chromatography. Based on these results, the sheath of T. nivea is hypothesized to be assembled from alternately beta-1,4-linked glucosaminoglucan grafted with unidentified deoxypentose. PMID- 22085753 TI - Structures and anti-HSV-2 activities of neutral polysaccharides from an edible plant, Basella rubra L. AB - Four neutral polysaccharides (BRN-1, BRN-2, BRN-3 and BRN-4) were isolated from the hot water extract of the aerial part of Basella rubra L. They were found to consist of a large amount of D-galactose (81.0-92.4%) and small amounts of L arabinose (5.4-7.8%), D-glucose (2.2-11.0%) and mannose (~2.9%). Linkage analysis revealed that all these neutral polysaccharides might be arabinogalactan type I polysaccharides in different molecular weight and chain length. Among them, only BRN-3 showed antiviral activity against herpes simplex virus type 2 (HSV-2) with 50% inhibitory concentration of 55 MUg/mL without showing the cytotoxicity up to 2300 MUg/mL. Furthermore, the main antiviral target of BRN-3 was shown to be the inhibition of virus adsorption to host cells. This is the first report on the neutral polysaccharide with anti-HSV-2 activity obtained from B. rubra L. PMID- 22085754 TI - Antioxidant activities of polysaccharides from Lentinus edodes and their significance for disease prevention. AB - The crude polysaccharide (LEP) was extracted by hot water from the fruiting bodies of Lentinus edodes, and further purified by DEAE-cellulose and Sepharose CL-6B chromatography, giving three polysaccharide fractions coded as LEPA1, LEPB1 and LEPC1. In this study, their chemical and physical characteristics of polysaccharide fractions and antioxidant capacities, including scavenging activity against hydroxyl radicals, superoxide radicals and Fe(2+)-chelating ability, were valuated. The results showed that LEPC1 exhibited significantly antioxidant activity at a concentration-dependent manner. Therefore these results indicated that the water-extractable polysaccharide fraction was a potent antioxidant and could be developed to be new health medicine for fighting against various human diseases. PMID- 22085755 TI - How does sucrose stabilize the native state of globular proteins? AB - It is well known that sucrose stabilizes the native state of globular proteins against both chemical denaturants and temperature. A largely accepted explanation of sucrose-induced stabilization is not yet emerged. It is shown that the same theoretical approach able to rationalize the occurrence of cold denaturation, the contrasting role of GdmCl and Gdm(2)SO(4), and the TMAO counteraction of urea denaturing activity [PCCP 12 (2010) 14245; PCCP 13 (2011) 12008; PCCP 13 (2011) 17689] works well also in the case of sucrose. The solvent-excluded volume effect plays the fundamental role because sucrose addition to water causes a marked increase in volume packing density due to the large size of sucrose molecules, that act as crowding agents. PMID- 22085756 TI - Characterization and application of a detergent-stable alkaline alpha-amylase from Bacillus subtilis strain AS-S01a. AB - A strain AS-S01a, capable of producing high-titer alkaline alpha-amylase, was isolated from a soil sample of Assam, India and was taxonomically identified as Bacillus subtilis strain AS-S01a. Optimized alpha-amylase yield by response surface method (RSM) was obtained as 799.0 U with a specific activity of 201.0 U/mg in a process control bioreactor. A 21.0 kDa alkaline alpha-amylase purified from this strain showed optimum activity at 55 degrees C and pH 9.0, and it produced high molecular weight oligosaccharides including small amount of glucose from starch as the end product. The K(m) and V(max) values for this enzyme towards starch were determined as 1.9 mg/ml and 198.21 MUmol/min/mg, respectively. The purified alpha-amylase retained its activity in presence of oxidant, surfactants, EDTA and various commercial laundry detergents, thus advocating its suitability for various industrial applications. PMID- 22085757 TI - Guided self-help concreteness training as an intervention for major depression in primary care: a Phase II randomized controlled trial. AB - BACKGROUND: The development of widely accessible, effective psychological interventions for depression is a priority. This randomized trial provides the first controlled data on an innovative cognitive bias modification (CBM) training guided self-help intervention for depression. METHOD: One hundred and twenty-one consecutively recruited participants meeting criteria for current major depression were randomly allocated to treatment as usual (TAU) or to TAU plus concreteness training (CNT) guided self-help or to TAU plus relaxation training (RT) guided self-help. CNT involved repeated practice at mental exercises designed to switch patients from an unhelpful abstract thinking habit to a helpful concrete thinking habit, thereby targeting depressogenic cognitive processes (rumination, overgeneralization). RESULTS: The addition of CNT to TAU significantly improved depressive symptoms at post-treatment [mean difference on the Hamilton Rating Scale for Depression (HAMD) 4.28, 95% confidence interval (CI) 1.29-7.26], 3- and 6-month follow-ups, and for rumination and overgeneralization post-treatment. There was no difference in the reduction of symptoms between CNT and RT (mean difference on the HAMD 1.98, 95% CI -1.14 to 5.11), although CNT significantly reduced rumination and overgeneralization relative to RT post-treatment, suggesting a specific benefit on these cognitive processes. CONCLUSIONS: This study provides preliminary evidence that CNT guided self-help may be a useful addition to TAU in treating major depression in primary care, although the effect was not significantly different from an existing active treatment (RT) matched for structural and common factors. Because of its relative brevity and distinct format, it may have value as an additional innovative approach to increase the accessibility of treatment choices for depression. PMID- 22085758 TI - Caffeine inhibits antinociception by acetaminophen in the formalin test by inhibiting spinal adenosine A1 receptors. AB - The present study examined effects of caffeine on antinociception by acetaminophen in the formalin test in mice. It demonstrates that caffeine 10mg/kg inhibits antinociception produced by acetaminophen 300 mg/kg i.p. against phase 2 flinches. Chronic administration of caffeine in the drinking water (0.1, 0.3g/l) for 8 days also inhibits the action of acetaminophen. The selective adenosine A(1) receptor antagonist DPCPX 1mg/kg i.p. mimics the action of caffeine, but the selective adenosine A(2A) receptor antagonist SCH58261 3mg/kg i.p. does not. While acetaminophen produced the same effect in mice that were +/+, +/- and -/- for adenosine A(1) receptors, inhibition of antinociception by caffeine was seen only in +/+ and +/- mice. A higher dose of caffeine, 40 mg/kg, produced an intrinsic antinociception against formalin-evoked flinches, an effect also seen when caffeine was administered intrathecally. SCH58261 30 nmol, but not DPCPX 10 nmol, also produced antinociception when administered intrathecally indicating involvement of adenosine A(2A) receptors in spinal antinociception. Caffeine reversal of acetaminophen results from actions in the spinal cord, as intrathecal DPCPX 10 nmol inhibited antinociception by systemic acetaminophen; this was also observed in +/+ but not in -/- adenosine A(1) receptor mice. We propose that spinal adenosine A(1) receptors contribute to the action of acetaminophen secondarily to involvement of descending serotonin pathways and release of adenosine within the spinal cord. Inhibition of acetaminophen antinociception by doses of caffeine relevant to dietary human intake levels suggests a more detailed consideration of acetaminophen-caffeine interactions in humans is warranted. PMID- 22085759 TI - pi-Conjugated cyanostilbene derivatives: a unique self-assembly motif for molecular nanostructures with enhanced emission and transport. AB - pi-Conjugated organic molecules represent an attractive platform for the design and fabrication of a wide range of nano- and microstructures for use in organic optoelectronics. The desirable optical and electrical properties of pi-conjugated molecules for these applications depend on their primary molecular structure and their intermolecular interactions such as molecular packing or ordering in the condensed states. Because of the difficulty in satisfying these rigorous structural requirements for photoluminescence and charge transport, the development of novel high-performance pi-conjugated systems for nano optoelectronics has remained a challenge. This Account describes our recent discovery of a novel class of self-assembling pi-conjugated organic molecules with a built-in molecular elastic twist. These molecules consist of a cyano substituted stilbenic pi-conjugated backbone and various terminal functional groups, and they offer excellent optical, electrical, and self-assembly properties for use in various nano-optoelectronic devices. The characteristic "twist elasticity" behavior of these molecules occurs in response to molecular interactions. These large torsional or conformational changes in the cyanostilbene backbone play an important role in achieving favorable intermolecular interactions that lead to both high photoluminescence and good charge carrier mobility in self-assembled nanostructures. Conventional pi conjugated molecules in the solid state typically show concentration (aggregation) fluorescence quenching. Initially, we describe the unique photoluminescence properties, aggregation-induced enhanced emission (AIEE), of these new cyanostilbene derivatives that elegantly circumvent these problems. These elastic twist pi-conjugated backbones serve as versatile scaffolds for the preparation of well-defined patterned nanosized architectures through facile self assembly processes. We discuss in particular detail the preparation of 1D nanowire structures through programmed self-assembly. This Account describes the importance of utilizing AIEE effects to explore optical device applications, such as organic semiconducting lasers (OSLs), optical memory, and sensors. We demonstrate the rich electronic properties, including the electrical conductivity, field-effect carrier mobility, and electroluminescence of highly crystalline 1D nanowire and coaxial donor-acceptor nanocable structures composed of elastic twist pi-conjugated molecules. The electronic properties were measured using various techniques, including current-voltage (I-V), conducting-probe atomic force microscopy (CP-AFM), and space-charge-limited-current (SCLC) measurements. We prepared and characterized several electronic device structures, including organic field-effect transistors (OFETs) and organic light-emitting field-effect transistors (OLETs). PMID- 22085761 TI - Reproduction numbers for epidemic models with households and other social structures. I. Definition and calculation of R0. AB - The basic reproduction number R(0) is one of the most important quantities in epidemiology. However, for epidemic models with explicit social structure involving small mixing units such as households, its definition is not straightforward and a wealth of other threshold parameters has appeared in the literature. In this paper, we use branching processes to define R(0), we apply this definition to models with households or other more complex social structures and we provide methods for calculating it. PMID- 22085760 TI - Evolution of anterior Hox regulatory elements among chordates. AB - BACKGROUND: The Hox family of transcription factors has a fundamental role in segmentation pathways and axial patterning of embryonic development and their clustered organization is linked with the regulatory mechanisms governing their coordinated expression along embryonic axes. Among chordates, of particular interest are the Hox paralogous genes in groups 1-4 since their expression is coupled to the control of regional identity in the anterior nervous system, where the highest structural diversity is observed. RESULTS: To investigate the degree of conservation in cis-regulatory components that form the basis of Hox expression in the anterior nervous system, we have used assays for transcriptional activity in ascidians and vertebrates to compare and contrast regulatory potential. We identified four regulatory sequences located near the CiHox1, CiHox2 and CiHox4 genes of the ascidian Ciona intestinalis which direct neural specific domains of expression. Using functional assays in Ciona and vertebrate embryos in combination with sequence analyses of enhancer fragments located in similar positions adjacent to Hox paralogy group genes, we compared the activity of these four Ciona cis-elements with a series of neural specific enhancers from the amphioxus Hox1-3 genes and from mouse Hox paralogous groups 1 4. CONCLUSIONS: This analysis revealed that Kreisler and Krox20 dependent enhancers critical in segmental regulation of the hindbrain appear to be specific for the vertebrate lineage. In contrast, neural enhancers that function as Hox response elements through the action of Hox/Pbx binding motifs have been conserved during chordate evolution. The functional assays reveal that these Hox response cis-elements are recognized by the regulatory components of different and extant species. Together, our results indicate that during chordate evolution, cis-elements dependent upon Hox/Pbx regulatory complexes, are responsible for key aspects of segmental Hox expression in neural tissue and appeared with urochordates after cephalochordate divergence. PMID- 22085762 TI - Consumer evaluation of complaint handling in the Dutch health insurance market. AB - BACKGROUND: How companies deal with complaints is a particularly challenging aspect in managing the quality of their service. In this study we test the direct and relative effects of service quality dimensions on consumer complaint satisfaction evaluations and trust in a company in the Dutch health insurance market. METHODS: A cross-sectional survey design was used. Survey data of 150 members of a Dutch insurance panel who lodged a complaint at their healthcare insurer within the past 12 months were surveyed. The data were collected using a questionnaire containing validated multi-item measures. These measures assess the service quality dimensions consisting of functional quality and technical quality and consumer complaint satisfaction evaluations consisting of complaint satisfaction and overall satisfaction with the company after complaint handling. Respondents' trust in a company after complaint handling was also measured. Using factor analysis, reliability and validity of the measures were assessed. Regression analysis was used to examine the relationships between these variables. RESULTS: Overall, results confirm the hypothesized direct and relative effects between the service quality dimensions and consumer complaint satisfaction evaluations and trust in the company. No support was found for the effect of technical quality on overall satisfaction with the company. This outcome might be driven by the context of our study; namely, consumers get in touch with a company to resolve a specific problem and therefore might focus more on complaint satisfaction and less on overall satisfaction with the company. CONCLUSIONS: Overall, the model we present is valid in the context of the Dutch health insurance market. Management is able to increase consumers' complaint satisfaction, overall satisfaction with the company, and trust in the company by improving elements of functional and technical quality. Furthermore, we show that functional and technical quality do not influence consumer satisfaction evaluations and trust in the company to the same extent. Therefore, it is important for managers to be aware of the type of consumer satisfaction they are measuring when evaluating the handling of complaints within their company. PMID- 22085763 TI - Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool. AB - INTRODUCTION: To develop a scoring method for quantifying nutrition risk in the intensive care unit (ICU). METHODS: A prospective, observational study of patients expected to stay > 24 hours. We collected data for key variables considered for inclusion in the score which included: age, baseline APACHE II, baseline SOFA score, number of comorbidities, days from hospital admission to ICU admission, Body Mass Index (BMI) < 20, estimated % oral intake in the week prior, weight loss in the last 3 months and serum interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) levels. Approximate quintiles of each variable were assigned points based on the strength of their association with 28 day mortality. RESULTS: A total of 597 patients were enrolled in this study. Based on the statistical significance in the multivariable model, the final score used all candidate variables except BMI, CRP, PCT, estimated percentage oral intake and weight loss. As the score increased, so did mortality rate and duration of mechanical ventilation. Logistic regression demonstrated that nutritional adequacy modifies the association between the score and 28 day mortality (p = 0.01). CONCLUSIONS: This scoring algorithm may be helpful in identifying critically ill patients most likely to benefit from aggressive nutrition therapy. PMID- 22085764 TI - Retrospective review of male breast cancer patients: analysis of tamoxifen related side-effects. AB - BACKGROUND: Approximately 2000 American men are diagnosed with breast cancer every year. Limited data are available evaluating toxicity of antihormonal treatments in male breast cancer patients. PATIENTS AND METHODS: We reviewed male breast cancer patients evaluated at our institution (1999-2009). Of 126 patients, 64 met the following inclusion criteria: stage I-III, treated with tamoxifen, at least one follow-up visit after starting tamoxifen. A descriptive analysis of toxic effects was carried out on these 64 patients. RESULTS: Median follow-up from start of tamoxifen therapy was 3.9 years (range 0.3-19.4 years). Median age at diagnosis was 61 years (range 30-79 years). Breakdown by stage: 29.7% (n = 19) stage I, 54.7% (n = 35) stage II, and 15.6% (n = 10) stage III. Thirty-four (53%) patients experienced one or more toxicity while taking tamoxifen. Most common toxic effects are weight gain (14 patients, 22%) and sexual dysfunction (14 patients, 22%). Thirteen (20.3%) patients discontinued tamoxifen due to toxicity: one ocular, one leg cramps, two neurocognitive deficits, two bone pain, three sexual dysfunction, and four thromboembolic events. CONCLUSIONS: To our knowledge, this is the largest study examining tamoxifen-related toxic effects among male breast cancer patients. Among male patients, there is a high rate of discontinuation of tamoxifen. Prospective studies of antihormonal agents in male breast cancer are warranted. PMID- 22085765 TI - Glycyrrhetinic acid protects mice from Staphylococcus aureus pneumonia. AB - In the present study, the antimicrobial activity of glycyrrhetinic acid (GA) against Staphylococcus aureus, and its influence on the production of S. aureus alpha-haemolysin (Hla) were investigated, along with the in vivo activity of GA against S. aureus-induced pneumonia. GA could not inhibit the growth of S. aureus, but the secretion of Hla by S. aureus was significantly inhibited by low concentrations of GA in a dose-dependent manner. Furthermore, in vivo data show that GA provides protection against staphylococcal pneumonia in a murine model system. PMID- 22085766 TI - A retrospective observational study on the efficacy of colistin by inhalation as compared to parenteral administration for the treatment of nosocomial pneumonia associated with multidrug-resistant Pseudomonas aeruginosa. AB - BACKGROUND: Colistin is used as last treatment option for pneumonia associated with multidrug-resistant (MDR) Pseudomonas spp.. Literature about the best administration mode (inhalation versus parenteral treatment) is lacking. METHODS: A retrospective study of 20 intensive care patients with a pneumonia associated with MDR P. aeruginosa receiving colistin sulphomethate sodium (Colistineb(r)) between 2007 and 2009 was performed. A strain was considered multidrug-resistant if it was resistant to at least 6 of the following antibiotics: piperacillin tazobactam, ceftazidime, cefepime, meropenem, aztreonam, ciprofloxacin, and amikacin. The administration mode, predicted mortality based on the SAPS3 score, SOFA score at onset of the colistin treatment, clinical and microbiological response, and mortality during the episode of the infection were analysed. The non parametric Kruskal-Wallis and Fisher's Exact test were used for statistical analysis of respectively the predicted mortality/SOFA score and mortality rate. RESULTS: Six patients received colistin by inhalation only, 5 were treated only parenterally, and 9 by a combination of both administration modes. All patients received concomitant beta-lactam therapy. The mean predicted mortalities were respectively 72%, 68%, and 69% (p = 0.91). SOFA scores at the onset of the treatment were also comparable (p = 0.87). Clinical response was favorable in all patients receiving colistin by inhalation (6/6) and in 40% (2/5) of the patients receiving colistin parenterally (p = 0.06). In the patients with colistin administered both via inhalation and parenterally, clinical response was favorable in 78% of the patients (7/9) (p = 0.27 as compared to the treatment group receiving colistin only parenterally). When all patients with inhalation therapy were compared to the group without inhalation therapy, a favorable clinical response was present in respectively 87% and 40% (p = 0.06). In none of the patients, the Pseudomonas spp. was eradicated from the follow-up cultures.All patients in the parenterally treated group died. None of the patients receiving colistin by inhalation, and 3 of 9 patients of the combination group eventually died (p = 0.002 and p = 0.03 respectively as compared to the group receiving colistin only parenterally). CONCLUSIONS: Aerosolized colistin could be beneficial as adjunctive treatment for the management of pneumonia due to MDR P. aeruginosa. PMID- 22085767 TI - Raccoon dog rabies surveillance and post-vaccination monitoring in Lithuania 2006 to 2010. AB - BACKGROUND: Oral rabies vaccination (ORV) in rabies infected regions should target the primary rabies vector species, which in Lithuania includes raccoon dogs as well as red foxes. Specific investigations on ORV in raccoon dogs are needed e.g. evaluation of vaccine effectiveness under field conditions. The objective of the current study was to investigate the efficacy of the ORV programme 2006-2010 in Lithuania by examining the number of rabies cases and estimating the prevalences of a tetracycline biomarker (TTC) and rabies virus antibodies in raccoon dogs. METHODS: From 2006 to 2010, 12.5 million rabies vaccine-baits were distributed by aircraft. Baiting occurred twice per year (spring and autumn), targeting raccoon dogs and red foxes in a 63,000 km2 area of Lithuania. The mandibles of raccoon dogs found dead or killed in the vaccination area were analyzed by fluorescence microscopy for the presence of the TTC. Rabies virus sera neutralizing anti-glycoprotein antibody titres were determined using an indirect ELISA method and seroconversion (> 0.5 EU/ml) rates were estimated. RESULTS: During the study period, 51.5% of raccoon dog mandibles were positive for TTC. 1688 of 3260 tested adults and 69 of 175 tested cubs were TTC positive. Forty-seven percent of raccoon dog serum samples were positive for rabies virus antibodies. 302 of 621 investigated adults and 33 of 95 investigated cubs were seropositive. In the same time 302 of 684 and 43 of 124 tested samples were TTC and ELISA positive in spring; whereas 1455 of 2751 and 292 of 592 tested samples were TTC and ELISA positive in autumn. There was a positive correlation between the number of TTC and antibody positive animals for both adult and cub groups. CONCLUSIONS: ORV was effective in reducing the prevalence of rabies in the raccoon dog population in Lithuania. The prevalence of rabies cases in raccoon dogs in Lithuania decreased from 60.7% in 2006-2007 to 6.5% in 2009-2010. PMID- 22085768 TI - A multigene phylogeny of Olpidium and its implications for early fungal evolution. AB - BACKGROUND: From a common ancestor with animals, the earliest fungi inherited flagellated zoospores for dispersal in water. Terrestrial fungi lost all flagellated stages and reproduce instead with nonmotile spores. Olpidium virulentus (= Olpidium brassicae), a unicellular fungus parasitizing vascular plant root cells, seemed anomalous. Although Olpidium produces zoospores, in previous phylogenetic studies it appeared nested among the terrestrial fungi. Its position was based mainly on ribosomal gene sequences and was not strongly supported. Our goal in this study was to use amino acid sequences from four genes to reconstruct the branching order of the early-diverging fungi with particular emphasis on the position of Olpidium. RESULTS: We concatenated sequences from the Ef-2, RPB1, RPB2 and actin loci for maximum likelihood and Bayesian analyses. In the resulting trees, Olpidium virulentus, O. bornovanus and non-flagellated terrestrial fungi formed a strongly supported clade. Topology tests rejected monophyly of the Olpidium species with any other clades of flagellated fungi. Placing Olpidium at the base of terrestrial fungi was also rejected. Within the terrestrial fungi, Olpidium formed a monophyletic group with the taxa traditionally classified in the phylum Zygomycota. Within Zygomycota, Mucoromycotina was robustly monophyletic. Although without bootstrap support, Monoblepharidomycetes, a small class of zoosporic fungi, diverged from the basal node in Fungi. The zoosporic phylum Blastocladiomycota appeared as the sister group to the terrestrial fungi plus Olpidium. CONCLUSIONS: This study provides strong support for Olpidium as the closest living flagellated relative of the terrestrial fungi. Appearing nested among hyphal fungi, Olpidium's unicellular thallus may have been derived from ancestral hyphae. Early in their evolution, terrestrial hyphal fungi may have reproduced with zoospores. PMID- 22085769 TI - A double antibody sandwich enzyme-linked immunosorbent assay for detection of secreted antigen 1 of Babesia microti using hamster model. AB - A double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) targeting secreted antigen 1 of Babesia microti (BmSA1) was developed for detection of B. microti infection. The optimized DAS-ELISA was sensitive enough to detect circulating BmSA1 by day 2 post-infection, in sequential sera of a hamster infected with B. microti. This detection was 4 days earlier than antibody detection by indirect ELISA. The kinetics of circulating BmSA1 coincided with the profile of parasitemia. The specificity of this assay was evaluated using sera from animals experimentally infected with different species of Babesia. The DAS ELISA had a higher sensitivity than the microscopic examination of Giemsa-stained blood smears for detection of the infection in hamsters. Taken together, these results indicated that BmSA1 could be a potential marker for surveillance of human babesiosis. PMID- 22085770 TI - Expression profile and subcellular localization of HslV, the proteasome related protease from Trypanosoma cruzi. AB - Trypanosoma cruzi is a rare example of an eukaryote that has genes for two threonine proteases: HslVU complex and 20S proteasome. HslVU is an ATP-dependent protease consisting of two multimeric components: the HslU ATPase and the HslV peptidase. In this study, we expressed and obtained specific antibodies to HslU and HslV recombinant proteins and demonstrated the interaction between HslU/HslV by coimmunoprecipitation. To evaluate the intracellular distribution of HslV in T. cruzi we used an immunofluorescence assay and ultrastructural localization by transmission electron microscopy. Both techniques demonstrated that HslV was localized in the kinetoplast of epimastigotes. We also analyzed the HslV/20S proteasome co-expression in Y, Berenice 62 (Be-62) and Berenice 78 (Be-78) T. cruzi strains. Our results showed that HslV and 20S proteasome are differently expressed in these strains. To investigate whether a proteasome inhibitor could modulate HslV and proteasome expressions, epimastigotes from T. cruzi were grown in the presence of PSI, a classical proteasome inhibitor. This result showed that while the level of expression of HslV/20S proteasome is not affected in Be-78 strain, in Y and Be-62 strains the presence of PSI induced a significantly increase in Hslv/20S proteasome expression. Together, these results suggest the coexistence of the protease HslVU and 20S proteasome in T. cruzi, reinforcing the hypothesis that non-lysosomal degradation pathways have an important role in T. cruzi biology. PMID- 22085771 TI - Aerobic degradation of sulfanilic acid using activated sludge. AB - This paper evaluates the aerobic degradation of sulfanilic acid (SA) by an acclimatized activated sludge. The sludge was enriched for over three months with SA (>500 mg/L) as the sole carbon and energy source and dissolved oxygen (DO, >5mg/L) as the primary electron acceptor. Effects of aeration rate (0-1.74 L/min), DO concentration (0-7 mg/L) and initial SA concentration (104-1085 mg/L) on SA biodegradation were quantified. A modified Haldane substrate inhibition model was used to obtain kinetic parameters of SA biodegradation and oxygen uptake rate (OUR). Positive linear correlations were obtained between OUR and SA degradation rate (R(2)>= 0.91). Over time, the culture consumed more oxygen per SA degraded, signifying a gradual improvement in SA mineralization (mass ratio of O(2): SA at day 30, 60 and 120 were 0.44, 0.51 and 0.78, respectively). The concomitant release of near stoichiometric quantity of sulphate (3.2 mmol SO(4)(2 ) released from 3.3 mmol SA) and the high chemical oxygen demand (COD) removal efficacy (97.1%) indicated that the enriched microbial consortia could drive the overall SA oxidation close to a complete mineralization. In contrast to other pure-culture systems, the ammonium released from the SA oxidation was predominately converted into nitrate, revealing the presence of ammonium oxidizing bacteria (AOB) in the mixed culture. No apparent inhibitory effect of SA on the nitrification was noted. This work also indicates that aerobic SA biodegradation could be monitored by real-time DO measurement. PMID- 22085772 TI - Detection of immune cell response to M. tuberculosis-specific antigens by quantitative polymerase chain reaction. AB - One third of the world's population is latently infected with Mycobacterium tuberculosis (Mtb) and up to 10% of infected individuals develop active tuberculosis (TB) in their lifetime. Among the major challenges in the control of TB is the implementation of sensitive methods for detection of latent tuberculosis infection (LTBI). Currently, in vitro interferon gamma release assays, yielding single value readout, are used as an alternative to the traditional tuberculin skin test for the diagnosis of LTBI. More complex characterization of immune status of LTBI individuals, however, is desirable for indication of LTBI subjects for preventative chemotherapy. Here we describe a quantitative polymerase chain reaction (qPCR) for determination of expression levels of 14 genes, additional to interferon gamma, which was applied for comparison of the specific Mtb-antigen immune response of blood cells from healthy, latently infected, and TB individuals. With the use of principal component analysis and discriminant analysis, a pattern of mRNA levels of 6 genes was identified, allowing discrimination of healthy individuals from active TB and LTBI subjects. These results open the way to development of multimarker qPCR for the detection of LTBI. PMID- 22085773 TI - Evaluation of the performance of 5 commercialized enzyme immunoassays for the detection of Taenia solium antibodies and for the diagnosis of neurocysticercosis. AB - This study aimed to evaluate 5 enzyme immunoassays for detecting human antibodies against Taenia solium in human serum and for the diagnosis of neurocysticercosis (NCC): DRGTM, RIDASCREENTM, NOVATECHTM, CYPRESSTM, and IVDTM. A collection of 114 reference serum samples were used. All sera were tested both by ELISA and by an immunoblot method (enzyme-linked immunoelectrotransfer blot [EITB]). When compared with EITB, the RidascreenTM test had the best positive concordance rate (85.1-91.2%) and the NovaLisa testTM showed the optimal negative concordance rate (93.7-95.6%). All tests had a sensitivity under 72% and a specificity above 60%. The best sensitivity was obtained using RidascreenTM test (71.4%). An optimal specificity was achieved by the NovaLisa testTM. T. solium-positive sera all cross-reacted with E. granulosus positive samples. In the commercial assays evaluated here, the most appropriate ELISA test for screening may be the RidascreenTM assay. Antibody detection seems to be not appropriate for NCC diagnosis because of its overall lack of sensitivity. PMID- 22085774 TI - Inducible galectins are expressed in the inflamed pharynx of the ascidian Ciona intestinalis. AB - Although ascidians belong to a key group in chordate phylogenesis, amino acid sequences of Ciona intestinalis galectin-CRDs (CiLgals-a and -b) have been retained too divergent from vertebrate galectins. In the present paper, to contribute in disclosing Bi-CRD galectin evolution a novel attempt was carried out on CiLgals-a and -b CRDs phylogenetic analysis, and their involvement in ascidian inflammatory responses was shown. CiLgals resulted aligned with Bi-CRD galectins from vertebrates (Xenopus tropicalis, Gallus gallus, Mus musculus, Homo sapiens), cephalochordates (Branchiostoma floridae), echinoderms (Strongylocentrotus purpuratus) and a mono-CRD galectin from the ascidian Clavelina picta. The CiLgals-a N-terminal and C-terminal CRDs contain the signature sequence involved in carbohydrate binding, whereas the CiLgals-b C-CRD presents only three out of seven key aminoacids and it could not be suitable as sugar binding motif. Sequence similarity between clusters suggests an evolutionary model based on CRD domain gene duplication and sequence diversification. In particular CiLgals-b N-CRD and C-CRD were similar to each other and both grouped with the ascidian C. picta mono-CRD. Homology modeling process shows a CiLgals molecular structure superimposed to chicken and mouse galectins. The CiLgals-a and CiLgals-b genes were upregulated by LPS inoculation suggesting that they are inducible and expressed in the inflamed pharynx as revealed by real-time PCR analysis. Finally, in situ hybridization and immunohistochemical assays showed their localization in the inflamed tissues, while immunoblotting analysis indicated that CiLgals can form oligomers. PMID- 22085775 TI - Comparison of three combined pharmacological approaches with tiotropium monotherapy in stable moderate to severe COPD: a systematic review. AB - BACKGROUND: Guidelines recommend the use of inhaled long-acting bronchodilators, inhaled corticosteroids (ICS) and their combinations for maintenance treatment of moderate to severe COPD. However, there are limited data supporting combination therapy. METHODS: This systematic review assessed the efficacy of three therapeutic approaches: tiotropium plus long-acting beta2-agonist (LABA) ("dual" therapy), LABA/ICS ("combined" therapy), and tiotropium plus LABA/ICS ("triple" therapy), all compared with tiotropium monotherapy. Randomized controlled trials were identified after a search of different databases of published and unpublished trials. RESULTS: Twenty trials (6803 participants) were included. "Dual" therapy showed significant improvements in forced volume in the first second (FEV(1)), health-related quality of life (HRQoL), and dyspnea. However, it failed to reduce the risk of COPD exacerbations. Compared with tiotropium, "combined" therapy presented modest but significant effects on FEV(1), HRQoL, and dyspnea. Again, there was no significant difference in exacerbations, but it was associated with a significant increase of serious adverse effects (SAE) (number need to treat for harm [NNTH] = 20; 95% CI: 11-119). Finally, "triple therapy" increased FEV(1), improved HRQoL (both benefits exceeded minimal important differences) and decrease COPD exacerbations in anon-significant way. (Odds ratio [OR] = 0.57; 95% CI: 0.24 to 1.37, p = 0.21). CONCLUSIONS: "Dual" and "triple" therapy seem like the most promising for patients with moderate to very severe COPD. However, data are still scarce and studies too short to generate a strong recommendation. Future studies should examine long-term efficacy and safety. PMID- 22085776 TI - Childhood trauma may combine synergistically with stimulant use rather than cannabis use to predict psychosis. PMID- 22085777 TI - Health care provider satisfaction with telephone consultations provided by pharmacists and physicians at the National HIV/AIDS Clinicians' Consultation Center. AB - BACKGROUND: The federally funded National HIV/AIDS Clinicians' Consultation Center (NCCC) offers US health care providers expert telephone consultations for managing HIV/AIDS and occupational exposures to blood-borne pathogens through 3 telephone services: the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline), the National HIV Telephone Consultation Service (Warmline), and the Perinatal HIV Hotline. Callers to the NCCC receive consultation from either a clinical pharmacist (PharmD) or a physician (MD) with HIV expertise. OBJECTIVE: To compare the satisfaction of NCCC callers who received clinical consultations from clinical pharmacists and physicians with HIV expertise. METHODS: We prospectively mailed 1256 satisfaction surveys to NCCC health care provider callers during a 7-month period. Survey recipients were not aware that satisfaction surveys compared PharmD and MD consultation services. Respondents rated their level of agreement with 8 statements about the quality of consultation, the quality of clinical information given, and future calls to the NCCC. RESULTS: Survey return rates were 43% for PEPline and 40% for Warmline and Perinatal HIV Hotline combined. Overall, caller satisfaction with the telephone consultation service was extremely high (>4 in all categories on a 1-5 Likert scale). There was no significant difference in PEPline caller satisfaction ratings between PharmD and MD consultations. Callers to the Warmline and Perinatal HIV Hotline agreed with all 8 satisfaction statements. For the following 3 statements, however, satisfaction was higher when Warmline and Perinatal HIV Hotline consultation was provided by an MD: "Overall, I was pleased with the quality of my consultation" (p = 0.04); "I would use this service again" (p < 0.02); and "I am likely to recommend this service to my colleagues" (p = 0.02). CONCLUSIONS: Health care provider callers to the NCCC were highly satisfied with the information obtained from this HIV/AIDS telephone consultation service. By measuring callers' survey response to PharmD and MD consultations, the importance of the clinicians' contributions to this advanced HIV/AIDS consultation service is documented. PMID- 22085778 TI - Systematic review and meta-analysis of efficacy, safety, and tolerability data from randomized controlled trials of drugs used to treat postherpetic neuralgia. AB - OBJECTIVE: To conduct a systematic review of available data from reports of randomized controlled trials on the efficacy, safety, and tolerability of drugs used to treat postherpetic neuralgia (PHN), a common type of neuropathic pain. DATA SOURCES: The MEDLINE (1950-June 30, 2009) and EMBASE (1974-June 30, 2009) databases were used to identify source studies, in conjunction with a review of reference citations from identified published reports. STUDY SELECTION AND DATA EXTRACTION: We selected all English-language reports of randomized placebo controlled trials of the efficacy, tolerability, and safety of drugs (oral or transdermal) used for treatment in patients with PHN. Studies with treatment duration less than 4 weeks were excluded. From each identified trial, we extracted information on (1) placebo-corrected percentage reductions in pain intensity from randomization to end of active treatment; (2) relative risks of withdrawal due to lack of efficacy; (3) relative risks of various adverse events; and (4) relative risks of withdrawal due to adverse events. DATA SYNTHESIS: Twelve reports of randomized controlled trials in patients with PHN were identified, involving 8 different agents (amitriptyline, capsaicin, divalproex sodium, gabapentin, morphine, nortriptyline, pregabalin, tramadol). Most studies were small, involving fewer than 200 patients. Pain intensity was reported to have been reduced significantly with all drugs (range: 13.8% [tramadol] to 42.4% [amitriptyline]); data were pooled using techniques of meta-analysis when information was available from more than 1 trial. No clinical trial reported a significant reduction in risk of withdrawal as a result of lack of efficacy. Analysis of adverse events was greatly limited by erratic and inconsistent reporting and wide variation in sample sizes. CONCLUSIONS: While available literature establishes the efficacy of 8 drugs in treatment of PHN, it does not provide adequate guidance as to which agents are best to treat this condition, in part because of inadequate reporting of data on tolerability and safety. PMID- 22085779 TI - Association between mental health conditions and rehospitalization, mortality, and functional outcomes in patients with stroke following inpatient rehabilitation. AB - BACKGROUND: Limited evidence exists regarding the association of pre-existing mental health conditions in patients with stroke and stroke outcomes such as rehospitalization, mortality, and function. We examined the association between mental health conditions and rehospitalization, mortality, and functional outcomes in patients with stroke following inpatient rehabilitation. METHODS: Our observational study used the 2001 VA Integrated Stroke Outcomes database of 2162 patients with stroke who underwent rehabilitation at a Veterans Affairs Medical Center. Separate models were fit to our outcome measures that included 6-month rehospitalization or death, 6-month mortality post-discharge, and functional outcomes post inpatient rehabilitation as a function of number and type of mental health conditions. The models controlled for patient socio-demographics, length of stay, functional status, and rehabilitation setting. RESULTS: Patients had an average age of 68 years. Patients with stroke and two or more mental health conditions were more likely to be readmitted or die compared to patients with no conditions (OR: 1.44, p = 0.04). Depression and anxiety were associated with a greater likelihood of rehospitalization or death (OR: 1.33, p = 0.04; OR:1.47, p = 0.03). Patients with anxiety were more likely to die at six months (OR: 2.49, p = 0.001). CONCLUSIONS: Patients with stroke with pre-existing mental health conditions may need additional psychotherapy interventions, which may potentially improve stroke outcomes post-hospitalization. PMID- 22085780 TI - The candidate Fu/HC gene in Botryllusschlosseri (Urochordata) and ascidians' historecognition--an oxymoron? AB - Allorecognition, distinguishing self from non-self allogeneic tissues is the underlying basis of innate immunity. In the colonial tunicate Botryllus schlosseri this historecognition is governed at a single genetic locus, Fu/HC (for fusibility/histocompatibility), with hundreds of co-dominantly expressed alleles. Several years ago, De Tomaso et al. (2005) have revolutionized the discipline of invertebrate allorecognition by describing a novel form of immune recognition in B. schlosseri, a non-vertebrate candidate histocompatibility gene (cFu/HC), revealing that allorecognition machinery in urochordates has nothing in common with the vertebrates' MHC-based histocompatibility. The authors reported absolute concordance of fusibility and cFu/HC genotype, predicted fusion/rejection outcomes in allorecognition settings from allelic polymorphism at the cFu/HC, also claiming cFu/HC gene expressions only in tissues directly engaged in histocompatibility. Here, we raise queries for the validity of the results and conclusions of De Tomaso et al. (2005) publication. Our reservations include discrepancies in the paper's results, including the perplexing absence of key sequencing material from public domains and above all, our own impugning outcomes. These include cloning efforts, in situ hybridization results, semi quantitative PCR outcomes, and the incongruence emerged between fusion/rejection profiles and cFu/HC segregated polymorphism that separately and cumulatively contradict the original publication. We conclude that Botryllus histocompatibility properties are not signaled in the claimed cFu/HC and that cFu/HC gene is unlikely the allodeterminant for Botryllus histocompatibility locus. Hence, the molecular nature of the Fu/HC locus in botryllid ascidians is still awaiting elucidation. PMID- 22085781 TI - The Drosophila larva as a tool to study gut-associated macrophages: PI3K regulates a discrete hemocyte population at the proventriculus. AB - Immune cells not only patrol the body in the circulation but also importantly, associate with specific tissues, such as the intestinal epithelium. The complex interactions between immune cells and their target tissues are difficult to study and simple, genetically tractable models are lacking. Here, we present the first thorough characterization of gut-associated macrophages in Drosophila larvae. We analyze their gene expression, morphology, development and lineage and importantly, demonstrate that they are functional (phagocytic) macrophages. We test their regulation by phosphoinositide 3-kinase (PI3K) and show evidence that this pathway regulates the population size of gut hemocytes and their phagocytic activity, reminiscent of recent findings in mammalian colitis models. Our data suggest that PI3K signaling modifies the adhesive properties of hemocytes, a possible mechanism for gut-hemocyte regulation. These results demonstrate the potential of the Drosophila larva as a simple tool to uncover mechanisms regulating recruitment and maintenance of innate immune cells at their target tissues. PMID- 22085782 TI - Report on the 23rd Annual Meeting of the Japanese Association for Developmental and Comparative Immunology (JADCI), 21-23 August 2011, Yokohama Institute for Earth Sciences, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Yokohama, Japan (Local organizer: Tadashi Maruyama, JAMSTEC). PMID- 22085783 TI - MIF from mussel: coding sequence, phylogeny, polymorphism, 3D model and regulation of expression. AB - Three macrophage migration inhibitory factor (MIF)-related sequences were identified from a Mytilus galloprovincialis EST library. The consensus sequence included a 5'-UTR of 32 nucleotides, the complete ORF of 345 nucleotides, and a 3'-UTR of 349 nucleotides. As for other MIFs, M. galloprovincialis ORF does not include any signal or C-terminus extensions. The translated sequence of 115 amino acids possesses a molecular mass of 12,681.4, a pI of 6.27 and a stability index of 21.48. Its 3D structure resembles human MIF except for one shorter alpha helix. Although evolutionary separated from ticks and vertebrates, Mg-MIF appeared to be closely related to Pinctada fucata and Haliotis, but not to Chlamys farreri and Biomphalaria glabrata. Numerous mutation points were observed within the Mg-MIF ORF, defining 11 amino acid variants within the mussels from Palavas-France and 14 amino acid variants within the mussels from Palermo-Italy. The 2 major variants from Palavas were identical to 2 of the 4 major variants from Palermo. In all the 18 Mg-MIF variants, residues involved in tautomerase and in oxidoreductase activities were conserved. Generally, one mussel expressed 2 Mg MIF amino acid sequences but with different frequencies of occurrence. Mg-MIF is constitutively expressed principally in hemocytes and in the mantle. In contrast to other animal models, Mg-MIF expression was always down regulated following challenge by bacteria and fungi, confirming previous data obtained with microarray. Down regulation started as soon as 1 h and Mg-MIF expression returned to background 9-48 h after the challenge. Exception was regarding the yeast, Candidaalbicans, down-regulation between 9 and 72 h, suggesting yeast and bacteria-filamentous fungi trigger different mechanisms of elimination. PMID- 22085785 TI - Reduction in hospital-wide mortality after implementation of a rapid response team: a long-term cohort study. AB - INTRODUCTION: Rapid response teams (RRTs) have been shown to reduce cardiopulmonary arrests outside the intensive care unit (ICU). Yet the utility of RRTs remains in question, as most large studies have failed to demonstrate a significant reduction in hospital-wide mortality after RRT implementation. METHODS: A cohort design with historical controls was used to determine the effect on hospital-wide mortality of an RRT in which clinical judgment, in addition to vital-signs criteria, was widely promoted as a key trigger for activation. All nonprisoner patients admitted to a tertiary referral public teaching hospital from 2003 through 2008 were included. In total, 77, 021 admissions before RRT implementation (2003 through 2005) and 79, 013 admissions after RRT implementation (2006 through 2008) were evaluated. The a priori primary outcome was unadjusted hospital-wide mortality. A Poisson regression model was then used to adjust for hospital-wide mortality trends over time. Secondary outcomes defined a priori were unadjusted out-of-ICU mortality and out-of-ICU cardiopulmonary-arrest codes. RESULTS: In total, 855 inpatient RRTs (10.8 per 1, 000 hospital-wide discharges) were activated during the 3-year postintervention period. Forty-seven percent of RRTs were activated for reasons of clinical judgment. Hospital-wide mortality decreased from 15.50 to 13.74 deaths per 1, 000 discharges after RRT implementation (relative risk, 0.887; 95% confidence interval (CI), 0.817 to 0.963; P = 0.004). After adjusting for inpatient mortality trends over time, the reduction in hospital-wide mortality remained statistically significant (relative risk, 0.825; 95% CI, 0.694 to 0.981; P = 0.029). Out-of-ICU mortality decreased from 7.08 to 4.61 deaths per 1, 000 discharges (relative risk, 0.651; 95% CI, 0.570 to 0.743; P < 0.001). Out-of-ICU cardiopulmonary-arrest codes decreased from 3.28 to 1.62 codes per 1, 000 discharges (relative risk, 0.493; 95% CI, 0.399 to 0.610; P < 0.001). CONCLUSIONS: Implementation of an RRT in which clinical judgment, in addition to vital-signs criteria, was widely cited as a rationale for activation, was associated with a significant reduction in hospital-wide mortality, out-of-ICU mortality, and out-of-ICU cardiopulmonary-arrest codes. The frequent use of clinical judgment as a criterion for RRT activation was associated with high RRT utilization. PMID- 22085784 TI - Bovine tuberculosis at a cattle-small ruminant-human interface in Meskan, Gurage region, Central Ethiopia. AB - BACKGROUND: Bovine tuberculosis (BTB) is endemic in Ethiopian cattle. The aim of this study was to assess BTB prevalence at an intensive contact interface in Meskan Woreda (district) in cattle, small ruminants and suspected TB lymphadenitis (TBLN) human patients. METHODS: The comparative intradermal test (CIDT) was carried out for all animals involved in the cross-sectional study and results interpreted using a > 4 mm and a > 2 mm cut-off. One PPD positive goat was slaughtered and lymph nodes subjected to culture and molecular typing. In the same villages, people with lymphadenitis were subjected to clinical examination. Fine needle aspirates (FNA) were taken from suspected TBLN and analyzed by smear microscopy and molecular typing. RESULTS: A total of 1214 cattle and 406 small ruminants were tested for BTB. In cattle, overall individual prevalence (> 2 mm cut-off) was 6.8% (CI: 5.4-8.5%) with 100% herd prevalence. Only three small ruminants (2 sheep and 1 goat) were reactors. The overall individual prevalence in small ruminants (> 2 mm cut-off) was 0.4% (CI: 0.03-5.1%) with 25% herd prevalence. Cattle from owners with PPD positive small ruminants were all PPD negative. 83% of the owners kept their sheep and goats inside their house at night and 5% drank regularly goat milk.FNAs were taken from 33 TBLN suspected cases out of a total of 127 screened individuals with lymph node swellings. Based on cytology results, 12 were confirmed TBLN cases. Nine out of 33 cultures were AFB positive. Culture positive samples were subjected to molecular typing and they all yielded M. tuberculosis. M. tuberculosis was also isolated from the goat that was slaughtered. CONCLUSIONS: This study highlighted a low BTB prevalence in sheep and goats despite intensive contact with cattle reactors. TBLN in humans was caused entirely by M. tuberculosis, the human pathogen. M. tuberculosis seems to circulate also in livestock but their role at the interface is unknown. PMID- 22085786 TI - The effects of homocysteine and folic acid on angiogenesis and VEGF expression during chicken vascular development. AB - Homocysteine (Hcy) has been implicated in the development of cardiovascular developmental defects. Additionally, in experimental studies, vasculotoxic properties of Hcy have been described. Although Hcy has been identified as a vascular pathogen, little is known about the direct effects Hcy exerts during early embryonic vascular development. Angiogenesis is a critical process involved in embryo survival and development. There are limited studies on the effects of Hcy on early embryonic vasculogenesis and angiogenesis. Folic acid (FA) is a B vitamin essential in embryo development, and FA supplementation may lead to reduced Hcy levels. Therefore, the purpose of our study was to explore the effects of Hcy and FA on early embryonic vascular development. Embryonic day (E) 3.5 chicken embryos were treated with a sham, Hcy or FA solution. We developed a computational program for systematic analysis of microscopic images obtained from the extra embryonic vascular beds. These results were combined with real-time PCR data on the expression of VEGF-A and its receptor in these vascular beds. Our data show that Hcy exposure inhibits early vascular development, displayed by a significant reduction of vessel area and altered composition of the vascular beds. Vascular beds of Hcy embryos for the greater part consisted of vessels of the smallest diameters, compared to middle size vessels in control and FA embryos. Hcy also reduced expression of VEGF-A and VEGFR-2. No significant effects of FA were found. We conclude that Hcy exposure causes impaired early extra embryonic vascular development, shown by altered composition of the vascular beds as well as reduced expression of VEGF-A and VEGFR-2. These effects of Hcy, and the consecutive cascade of events, may be involved in the development of cardiovascular developmental defects. PMID- 22085787 TI - Searching for differences in the behavioural response of piglet groups subjected to novel situations. AB - The Backtest (BT), the Open Field (OF) and the Novel Object (NO) tests have been used to identify individual reaction patterns in piglets and to measure parameters that previous studies have shown to be correlated to the coping strategies of animals. The BT allows for the classification of piglets into two different "coping styles": high-resisting (HR) and low-resisting (LR), which respectively correspond to a (pro-)active and passive (or reactive) behavioural response. During previous research, the subjects were tested singularly, so the aim of this study was to investigate if differences between HR and LR animals could be detected when piglets are tested in a group using the OP and NO tests. A total of 132 piglets were subjected to the BT and then were housed in groups consisting of four individuals each so as to obtain HR pens, LR pens and mixed pens. We found differences in the pigs' behaviour during the OF and the NO tests and according to the type of group. Individual differences in the behavioural response of piglets to the Backtest were not predictive of the behavioural response of the animals subjected to the OF or to NO tests. Our results show that there are no relevant differences between HR and LR piglets when they are subjected in a group to novel situations. PMID- 22085788 TI - Bats' avoidance of real and virtual objects: implications for the sonar coding of object size. AB - Fast movement in complex environments requires the controlled evasion of obstacles. Sonar-based obstacle evasion involves analysing the acoustic features of object-echoes (e.g., echo amplitude) that correlate with this object's physical features (e.g., object size). Here, we investigated sonar-based obstacle evasion in bats emerging in groups from their day roost. Using video-recordings, we first show that the bats evaded a small real object (ultrasonic loudspeaker) despite the familiar flight situation. Secondly, we studied the sonar coding of object size by adding a larger virtual object. The virtual object echo was generated by real-time convolution of the bats' calls with the acoustic impulse response of a large spherical disc and played from the loudspeaker. Contrary to the real object, the virtual object did not elicit evasive flight, despite the spectro-temporal similarity of real and virtual object echoes. Yet, their spatial echo features differ: virtual object echoes lack the spread of angles of incidence from which the echoes of large objects arrive at a bat's ears (sonar aperture). We hypothesise that this mismatch of spectro-temporal and spatial echo features caused the lack of virtual object evasion and suggest that the sonar aperture of object echoscapes contributes to the sonar coding of object size. PMID- 22085789 TI - Dissociation between seeing and acting: insights from common marmosets (Callithrix jacchus). AB - Perception-based measures often reveal much earlier competencies than action based approaches. We explored this phenomenon generally labeled as "knowledge dissociation" in 28 common marmoset monkeys (Callithrix jacchus) using a paradigm where subjects had to localize a food item dropped down an opaque tube. Experiments 1 and 2 assessed common marmoset monkeys' gravity bias in an action based version of the tubes task. Experiments 3 and 4 investigated whether marmosets' performance increases in an action-free task context where they simply look at objects falling down a tube. The results suggest that common marmosets have some intuition of continuity/solidity constraints when tested with perception based measures even though these principles do not appear to guide their search for falling objects. PMID- 22085790 TI - Use of a barbed tool by an adult and a juvenile woodpecker finch (Cactospiza pallida). AB - Here we describe the modification and use of a new tool type in the woodpecker finch (Cactospiza pallida). This species is known to habitually use twigs or cactus spines to extract arthropods out of tree holes. We observed an adult and a juvenile bird using several barbed twigs from introduced blackberry bushes (Rubus niveus) which the adult bird had first modified by removing leaves and side twigs. The barbs of blackberry tools provide a novel functional feature not present in tools made from native plants and de-leafing of twigs never has been observed before. Both birds were observed using several of these tools to extract prey from under the bark of the native scalesia tree (Scalesia penduculta). They oriented the twigs such that the barbs pointed towards themselves; this rendered the barbs functional as they could be used to drag prey out of a crevice. The juvenile bird first watched the adult using the tool and then used the tool that the adult bird had left under the bark at the same location and in the same way as the adult. Our observation highlights the fact that opportunities for the transmission of social information do occur in the wild and indicates that woodpecker finches are flexible in their choice of tool material and tool modification. PMID- 22085791 TI - Is optimism optimal? Functional causes of apparent behavioural biases. AB - We review the use of the terms 'optimism' and 'pessimism' to characterize particular types of behaviour in non-human animals. Animals can certainly behave as though they are optimistic or pessimistic with respect to specific motivations, as documented by an extensive range of examples in the literature. However, in surveying such examples we find that these terms are often poorly defined and are liable to lead to confusion. Furthermore, when considering behaviour within the framework of optimal decision theory using appropriate currencies, it is often misleading to describe animals as optimistic or pessimistic. There are two common misunderstandings. First, some apparent cases of biased behaviour result from misidentifying the currencies and pay-offs the animals should be maximising. Second, actions that do not maximise short-term pay offs have sometimes been described as optimistic or pessimistic when in fact they are optimal in the long term; we show how such situations can be understood from the perspective of bandit models. Rather than describing suboptimal, unrealistic behaviour, the terms optimism and pessimism are better restricted to informal usage. Our review highlights the importance of choosing the relevant currency when attempting to predict the action of natural selection. PMID- 22085792 TI - Emergence and evolution of the glycoprotein hormone and neurotrophin gene families in vertebrates. AB - BACKGROUND: The three vertebrate pituitary glycoprotein hormones (GPH) are heterodimers of a common alpha and a specific beta subunit. In human, they are located on different chromosomes but in a similar genomic environment. We took advantage of the availability of genomic and EST data from two cartilaginous fish species as well as from two lamprey species to identify their repertoire of neurotrophin, lin7 and KCNA gene family members which are in the close environment of gphbeta. Gphalpha and gphbeta are absent outside vertebrates but are related to two genes present in both protostomes and deuterostomes that were named gpa2 and gpb5. Genomic organization and functional characteristics of their protein products suggested that gphalpha and gphbeta might have been generated concomitantly by a duplication of gpa2 and gpb5 just prior to the radiation of vertebrates. To have a better insight into this process we used new genomic resources and tools to characterize the ancestral environment before the duplication occurred. RESULTS: An almost similar repertoire of genes was characterized in cartilaginous fishes as in tetrapods. Data in lampreys are either incomplete or the result of specific duplications and/or deletions but a scenario for the evolution of this genomic environment in vertebrates could be proposed. A number of genes were identified in the amphioxus genome that helped in reconstructing the ancestral environment of gpa2 and gpb5 and in describing the evolution of this environment in vertebrates. CONCLUSION: Our model suggests that vertebrate gphalpha and gphbeta were generated by a specific local duplication of the ancestral forms of gpa2 and gpb5, followed by a translocation of gphbeta to a new environment whereas gphalpha was retained in the gpa2-gpb5 locus. The two rounds of whole genome duplication that occurred early in the evolution of vertebrates generated four paralogues of each gene but secondary gene losses or lineage specific duplications together with genomic rearrangements have resulted in the present organization of these genes, which differs between vertebrate lineages. PMID- 22085793 TI - Angiogenic biomarkers predict the occurrence of digital ulcers in systemic sclerosis. AB - OBJECTIVE: To evaluate the possible merit of endothelial markers for the prediction of ischaemic digital ulcers in patients with systemic sclerosis (SSc). METHODS: Circulating endothelial progenitor cells (EPC), circulating endothelial cells and serum levels of placental growth factor (PlGF), soluble vascular adhesion molecule and vascular endothelial growth factor were measured in a prospective cohort of 100 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. RESULTS: After the follow-up period, 17 patients developed new digital ulcers. By multivariate analysis focused on biomarkers, high PlGF serum levels and low EPC counts were identified as predictors of the occurrence of at least one new digital ulcer. In a secondary model including biomarkers together with clinical SSc characteristics all predictors of digital ulcers defined by p<=0.1 in univariate analysis, high PlGF serum levels (HR 7.26, 95% CI 1.92 to 27.41) and a history of digital ulcers (HR 9.32, 95% CI 1.51 to 59.83) were identified as independent predictors of a new digital ulcer. In an alternative model excluding patients with a history of digital ulcers at baseline, high PlGF serum levels (HR 13.46, 95% CI 1.58 to 114.73) and low EPC counts (HR 7.95, 95% CI 2.09 to 30.09) remained predictive of new digital ulcer occurrence during follow-up. CONCLUSION: This study identified high PlGF serum levels and low circulating EPC counts as predictors of new digital ulcers in SSc. It highlights the critical role of angiogenesis in this vascular outcome. These markers may improve digital ulcer risk stratification and therefore allow earlier therapeutic intervention. PMID- 22085794 TI - Validity of the top-down approach of inverse dynamics analysis in fast and large rotational trunk movements. AB - This study investigated the validity of the top-down approach of inverse dynamics analysis in fast and large rotational movements of the trunk about three orthogonal axes of the pelvis for nine male collegiate students. The maximum angles of the upper trunk relative to the pelvis were approximately 47 degrees , 49 degrees , 32 degrees , and 55 degrees for lateral bending, flexion, extension, and axial rotation, respectively, with maximum angular velocities of 209 degrees /s, 201 degrees /s, 145 degrees /s, and 288 degrees /s, respectively. The pelvic moments about the axes during the movements were determined using the top-down and bottom-up approaches of inverse dynamics and compared between the two approaches. Three body segment inertial parameter sets were estimated using anthropometric data sets (Ae et al., Biomechanism 11, 1992; De Leva, J Biomech, 1996; Dumas et al., J Biomech, 2007). The root-mean-square errors of the moments and the absolute errors of the peaks of the moments were generally smaller than 10 N.m. The results suggest that the pelvic moment in motions involving fast and large trunk movements can be determined with a certain level of validity using the top-down approach in which the trunk is modeled as two or three rigid-link segments. PMID- 22085796 TI - Intraerythrocytic stages of Plasmodium falciparum biosynthesize vitamin E. AB - The 2-C-methyl-D-erythritol-4-phosphate and shikimate pathways were found to be active in Plasmodium falciparum and both can result in vitamin E biosynthesis in plants and algae. This study biochemically confirmed vitamin E biosynthesis in the malaria parasite, which can be inhibited by usnic acid. Furthermore, we found evidence pointing to a role of this vitamin in infected erythrocytes. These findings not only contribute to current understanding of P. falciparum biology but also reveal a pathway that could serve as a chemotherapeutic target. PMID- 22085797 TI - Imaging periprosthetic osteolysis around total knee arthroplasties using a human cadaver model. AB - We examined the sensitivity and accuracy of measuring osteolysis around total knee arthroplasty (TKA) on radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) in a cadaver model. Fifty-four simulated osteolytic defects ranging from 0.7 to 14 cm(3) were created in 6 cadaver knees implanted with either a cemented or an uncemented TKA. Three blinded investigators assessed the presence, location, and volume of defects on radiographs and CT and MRI scans with metal reduction protocols. Both CT and MRI had significantly higher sensitivities and specificities than did plain radiographs (P < .005). Overall, there was no difference in the accuracy of defect volume measurements between CT and MRI (P = .574). This study demonstrates the limitations of radiographs and the high sensitivity and specificity of both CT and MRI in assessing osteolysis around TKA. PMID- 22085798 TI - Long-term femoral bone remodeling after cemented hip arthroplasty with the Muller straight stem in the operated and nonoperated femora. AB - We investigated the cortical bone changes in 35 patients with total hip arthroplasty operated on only for osteoarthritis with more than 10 years of follow-up and with nonrevised femoral components and without radiologic signs of loosening. The mean follow-up was 16 +/- 5 years. The thicknesses of femoral cortices were measured medially and laterally at 6 levels from the first postoperative and the last follow-up x-rays. A comparison with 10 patients who had a nonoperated contralateral hip was performed. We found a significant decrease in cortical thicknesses in total hip arthroplasty. The cortical thinning was significant at all periprosthetic levels but less expressed distally. Prosthetic femora were associated with greater cortical thinning as compared with the contralateral nonoperated femora, exceeding that caused by natural aging. PMID- 22085795 TI - The susceptibility of the retina to photochemical damage from visible light. AB - The photoreceptor/RPE complex must maintain a delicate balance between maximizing the absorption of photons for vision and retinal image quality while simultaneously minimizing the risk of photodamage when exposed to bright light. We review the recent discovery of two new effects of light exposure on the photoreceptor/RPE complex in the context of current thinking about the causes of retinal phototoxicity. These effects are autofluorescence photobleaching in which exposure to bright light reduces lipofuscin autofluorescence and, at higher light levels, RPE disruption in which the pattern of autofluorescence is permanently altered following light exposure. Both effects occur following exposure to visible light at irradiances that were previously thought to be safe. Photopigment, retinoids involved in the visual cycle, and bisretinoids in lipofuscin have been implicated as possible photosensitizers for photochemical damage. The mechanism of RPE disruption may follow either of these paths. On the other hand, autofluorescence photobleaching is likely an indicator of photooxidation of lipofuscin. The permanent changes inherent in RPE disruption might require modification of the light safety standards. AF photobleaching recovers after several hours although the mechanisms by which this occurs are not yet clear. Understanding the mechanisms of phototoxicity is all the more important given the potential for increased susceptibility in the presence of ocular diseases that affect either the visual cycle and/or lipofuscin accumulation. In addition, knowledge of photochemical mechanisms can improve our understanding of some disease processes that may be influenced by light exposure, such as some forms of Leber's congenital amaurosis, and aid in the development of new therapies. Such treatment prior to intentional light exposures, as in ophthalmic examinations or surgeries, could provide an effective preventative strategy. PMID- 22085799 TI - Reprint of: 'Brain insulin signaling: A key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes'. AB - Understanding of the role of insulin in the brain has gradually expanded, from initial conceptions of the brain as insulin-insensitive through identification of a role in regulation of feeding, to recent demonstration of insulin as a key component of hippocampal memory processes. Conversely, systemic insulin resistance such as that seen in type 2 diabetes is associated with a range of cognitive and neural deficits. Here we review the evidence for insulin as a cognitive and neural modulator, including potential effector mechanisms, and examine the impact that type 2 diabetes has on these mechanisms in order to identify likely bases for the cognitive impairments seen in type 2 diabetic patients. PMID- 22085801 TI - Improved sensitivity of an interferon-gamma release assay (T-SPOT.TBTM) in combination with tuberculin skin test for the diagnosis of latent tuberculosis in the presence of HIV co-infection. AB - BACKGROUND: Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection. METHODS: IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study. RESULTS: 64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range [IQR] 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/MUl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older). CONCLUSIONS: T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment. PMID- 22085802 TI - Automatic discrimination between safe and unsafe swallowing using a reputation based classifier. AB - BACKGROUND: Swallowing accelerometry has been suggested as a potential non invasive tool for bedside dysphagia screening. Various vibratory signal features and complementary measurement modalities have been put forth in the literature for the potential discrimination between safe and unsafe swallowing. To date, automatic classification of swallowing accelerometry has exclusively involved a single-axis of vibration although a second axis is known to contain additional information about the nature of the swallow. Furthermore, the only published attempt at automatic classification in adult patients has been based on a small sample of swallowing vibrations. METHODS: In this paper, a large corpus of dual axis accelerometric signals were collected from 30 older adults (aged 65.47 +/- 13.4 years, 15 male) referred to videofluoroscopic examination on the suspicion of dysphagia. We invoked a reputation-based classifier combination to automatically categorize the dual-axis accelerometric signals into safe and unsafe swallows, as labeled via videofluoroscopic review. From these participants, a total of 224 swallowing samples were obtained, 164 of which were labeled as unsafe swallows (swallows where the bolus entered the airway) and 60 as safe swallows. Three separate support vector machine (SVM) classifiers and eight different features were selected for classification. RESULTS: With selected time, frequency and information theoretic features, the reputation-based algorithm distinguished between safe and unsafe swallowing with promising accuracy (80.48 +/- 5.0%), high sensitivity (97.1 +/- 2%) and modest specificity (64 +/- 8.8%). Interpretation of the most discriminatory features revealed that in general, unsafe swallows had lower mean vibration amplitude and faster autocorrelation decay, suggestive of decreased hyoid excursion and compromised coordination, respectively. Further, owing to its performance-based weighting of component classifiers, the static reputation-based algorithm outperformed the democratic majority voting algorithm on this clinical data set. CONCLUSION: Given its computational efficiency and high sensitivity, reputation-based classification of dual-axis accelerometry ought to be considered in future developments of a point-of-care swallow assessment where clinical informatics are desired. PMID- 22085800 TI - Interacting brain systems modulate memory consolidation. AB - Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders. PMID- 22085805 TI - Evaluation of algorithms for microperfusion assessment by fast simulations of laser Doppler power spectral density. AB - In classical laser Doppler (LD) perfusion measurements, zeroth- and first-order moments of the power spectral density of the LD signal are utilized for the calculation of a signal corresponding to the concentration, speed and flow of red blood cells (RBCs). We have analysed the nonlinearities of the moments in relation to RBC speed distributions, parameters of filters utilized in LD instruments and the signal-to-noise ratio. We have developed a new method for fast simulation of the spectrum of the LD signal. The method is based on a superposition of analytically calculated Doppler shift probability distributions derived for the assumed light scattering phase function. We have validated the method by a comparison of the analytically calculated spectra with results of Monte Carlo (MC) simulations. For the semi-infinite, homogeneous medium and the single Doppler scattering regime, the analytical calculation describes LD spectra with the same accuracy as the MC simulation. The method allows for simulating the LD signal in time domain and furthermore analysing the index of perfusion for the assumed wavelength of the light, optical properties of the tissue and concentration of RBCs. Fast simulations of the LD signal in time domain and its frequency spectrum can be utilized in applications where knowledge of the LD photocurrent is required, e.g. in the development of detectors for tissue microperfusion monitoring or in measurements of the LD autocorrelation function for perfusion measurements. The presented fast method for LD spectra calculation can be used as a tool for evaluation of signal processing algorithms used in the LD method and/or for the development of new algorithms of the LD flowmetry and imaging. We analysed LD spectra obtained by analytical calculations using a classical algorithm applied in classical LD perfusion measurements. We observed nonlinearity of the first moment M1 for low and high speeds of particles (v < 2 mm s-1, v > 10 mm s-1). It was also noted that the first moment M(1) is less sensitive to the change of the mean RBC speed for flat speed distributions. The low-pass filter frequency f2 implemented in the LD instrument has a significant influence on the first moment of the spectrum. In particular, for a cut-off frequency lower than 10 kHz the M1 value is strongly underestimated. PMID- 22085804 TI - Effects of comorbidity and early age of onset in young people with Bipolar Disorder on self harming behaviour and suicide attempts. AB - BACKGROUND: The age of the first episode of illness in Bipolar Disorder has been shown to be an important predictor of outcome with early onset, particularly onset before puberty, associated with greater comorbidity, a poorer quality of life and greatest impairment in functioning. METHODS: Baseline data from a psychotherapy study was used to examine the prevalence of other comorbid psychiatric conditions and the impact of onset at an early age on both self harming behaviour and suicide attempts in young people with Bipolar Disorder. RESULTS: This study of 100 adolescents and young adults (aged 15-36 years) with Bipolar Disorder showed that comorbid conditions were very common, even at the start of their bipolar illness. Comorbidity increased as the age of onset decreased with very early onset (<13 years) patients bearing the greatest burden of disease. Greater comorbidity also significantly increased the risk of having self harmed and attempted suicide with high lethal intent. Self harming behaviour was predicted by having a lifetime diagnoses of Borderline Personality Disorder and Panic Disorder along with an early age of onset of Bipolar Disorder. In contrast, previous suicide attempts were predicted by greater comorbidity and not by very early (<13 years) age of onset. PMID- 22085803 TI - Design and methodological considerations of an effectiveness trial of a computer assisted intervention: an example from the NIDA Clinical Trials Network. AB - Computer-assisted interventions hold the promise of minimizing two problems that are ubiquitous in substance abuse treatment: the lack of ready access to treatment and the challenges to providing empirically-supported treatments. Reviews of research on computer-assisted treatments for mental health and substance abuse report promising findings, but study quality and methodological limitations remain an issue. In addition, relatively few computer-assisted treatments have been tested among illicit substance users. This manuscript describes the methodological considerations of a multi-site effectiveness trial conducted within the National Institute on Drug Abuse's (NIDA's) National Drug Abuse Treatment Clinical Trials Network (CTN). The study is evaluating a web based version of the Community Reinforcement Approach, in addition to prize-based contingency management, among 500 participants enrolled in 10 outpatient substance abuse treatment programs. Several potential effectiveness trial designs were considered and the rationale for the choice of design in this study is described. The study uses a randomized controlled design (with independent treatment arm allocation), intention-to-treat primary outcome analysis, biological markers for the primary outcome of abstinence, long-term follow-up assessments, precise measurement of intervention dose, and a cost-effectiveness analysis. Input from community providers during protocol development highlighted potential concerns and helped to address issues of practicality and feasibility. Collaboration between providers and investigators supports the utility of infrastructures that enhance research partnerships to facilitate effectiveness trials and dissemination of promising, technologically innovative treatments. Outcomes from this study will further the empirical knowledge base on the effectiveness and cost-effectiveness of computer-assisted treatment in clinical treatment settings. PMID- 22085806 TI - Poisoning and non-poisoning oxygen on Cu(410). AB - We have investigated ethene and oxygen co-adsorption on Cu(410) by high resolution electron energy loss spectroscopy. We find that these two species compete for the adsorption sites and that pre-exposure to oxygen affects ethene adsorption more or less strongly depending on oxygen coverage and the kind of occupied sites. The c(2 * 2) O overlayer is inert with respect to ethene adsorption, while when some oxygen is removed by thermally induced subsurface incorporation, ethene chemisorption is restored. The latter species also adsorbs on the disordered oxygen phase formed when O(2) is dosed at low crystal temperature. Contrary to the bare surface case, most of the ethene ends up in a pi-bonded configuration. Dehydrogenation occurs, too, albeit as a minority channel. The so-produced carbon reacts already at low temperature with adsorbed oxygen to yield carbon monoxide, which desorbs around 190 K. PMID- 22085807 TI - Whole genome resequencing of black Angus and Holstein cattle for SNP and CNV discovery. AB - BACKGROUND: One of the goals of livestock genomics research is to identify the genetic differences responsible for variation in phenotypic traits, particularly those of economic importance. Characterizing the genetic variation in livestock species is an important step towards linking genes or genomic regions with phenotypes. The completion of the bovine genome sequence and recent advances in DNA sequencing technology allow for in-depth characterization of the genetic variations present in cattle. Here we describe the whole-genome resequencing of two Bos taurus bulls from distinct breeds for the purpose of identifying and annotating novel forms of genetic variation in cattle. RESULTS: The genomes of a Black Angus bull and a Holstein bull were sequenced to 22-fold and 19-fold coverage, respectively, using the ABI SOLiD system. Comparisons of the sequences with the Btau4.0 reference assembly yielded 7 million single nucleotide polymorphisms (SNPs), 24% of which were identified in both animals. Of the total SNPs found in Holstein, Black Angus, and in both animals, 81%, 81%, and 75% respectively are novel. In-depth annotations of the data identified more than 16 thousand distinct non-synonymous SNPs (85% novel) between the two datasets. Alignments between the SNP-altered proteins and orthologues from numerous species indicate that many of the SNPs alter well-conserved amino acids. Several SNPs predicted to create or remove stop codons were also found. A comparison between the sequencing SNPs and genotyping results from the BovineHD high-density genotyping chip indicates a detection rate of 91% for homozygous SNPs and 81% for heterozygous SNPs. The false positive rate is estimated to be about 2% for both the Black Angus and Holstein SNP sets, based on follow-up genotyping of 422 and 427 SNPs, respectively. Comparisons of read depth between the two bulls along the reference assembly identified 790 putative copy-number variations (CNVs). Ten randomly selected CNVs, five genic and five non-genic, were successfully validated using quantitative real-time PCR. The CNVs are enriched for immune system genes and include genes that may contribute to lactation capacity. The majority of the CNVs (69%) were detected as regions with higher abundance in the Holstein bull. CONCLUSIONS: Substantial genetic differences exist between the Black Angus and Holstein animals sequenced in this work and the Hereford reference sequence, and some of this variation is predicted to affect evolutionarily conserved amino acids or gene copy number. The deeply annotated SNPs and CNVs identified in this resequencing study can serve as useful genetic tools, and as candidates in searches for phenotype-altering DNA differences. PMID- 22085808 TI - Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N(2)O). AB - OBJECTIVES: Occupational exposure to nitrous oxide (N(2)O) and/or halogenated hydrocarbons has been suggested to induce damage of genetic material, but the underlying mechanisms remain obscure. This study investigated the role of oxidative processes in the genotoxicity associated with exposure to waste anaesthetic gases. METHODS: The study was performed in 36 female nurses and in 36 unexposed female health care workers matched for age and employment duration. Genotoxic effects were examined by Comet test modification employing formamidopyrimidine glycosylase (FPG) that allows assessment of oxidative DNA damage. Reactive oxygen species (ROS) in leukocytes were investigated by fluorescence spectroscopy with 2',7'-dichlorofluorescin diacetate. Oxidative stress markers including 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), thiobarbituric acid-reacive substances (TBARS), alpha-tocopherol, and glutathione peroxidise (GPX) activity were measured immuno- or colorimetrically. N(2)O, sevoflurane and isoflurane were monitored by gas chromatography and mass spectrometry. RESULTS: The study documents for the first time the positive correlation between the oxidative DNA damage and the N(2)O levels in the ambient air. By contrast, no association was observed between genotoxic effects and sevoflurane or isoflurane. In addition, ROS generation and plasma and urine concentrations of TBARS and 8-iso-PGF(2alpha), respectively, were elevated, while GPX activity was reduced in nurses exposed to waste anaesthetic gases. Path analysis pointed to a causal relationship between N(2)O exposure, oxidative stress and DNA damage. CONCLUSION: Occupational exposure to N(2)O is associated with increased oxidative DNA damage and the level of exposure plays a critical role in this regard. Increased oxidative stress may represent a mechanistic link between chronic N(2)O exposure and genotoxicity. PMID- 22085809 TI - Functional relevance of miRNA sequences in human disease. AB - MicroRNA (miRNA) processing in the cytoplasm produces a miRNA duplex containing the forward, miRNA strand and the reverse, miRNA strand, which was thought to be degraded. However, recent evidence is challenging this dogma that miRNA is simply a non-functional byproduct of miRNA biogenesis. We present a comprehensive review of evidence that miRNA plays a significant role in cellular function and assembled a table outlining all of the publications before September 2011 that have reported on miRNA activity in human disease. Furthermore, we will present unexpected diagnostic and therapeutic implications due to the active miRNA status. PMID- 22085810 TI - A target-orientated algorithm for regional citrate-calcium anticoagulation in extracorporeal therapies. AB - BACKGROUND: Citrate anticoagulation offers several advantages in comparison to conventional anticoagulation. Most algorithms for regional citrate-calcium anticoagulation are based on citrate and calcium chloride infusion coupled in a fixed proportion to the blood flow without considering the hematocrit (Hct)/plasma flow or the filter clearance of citrate and calcium. METHODS: The aim of this study was to develop an algorithm for optimized citrate anticoagulation in extracorporeal therapies such as dialysis. A mathematical model was developed to calculate the volume of citrate infusion required to achieve a desired ionized calcium (iCa) target level in the extracorporeal circuit and to restore the total calcium level to a physiological value. RESULTS: The model was validated by correlation analyses for different blood Hct values and shows an excellent fit to the laboratory measurements. CONCLUSION: The results for both iCa target concentrations, namely those after citrate and calcium infusion, proved that the software algorithm adapts well to variable treatment parameters. PMID- 22085811 TI - Comparison between overground and dynamometer manual wheelchair propulsion. AB - Laboratory-based simulators afford many advantages for studying physiology and biomechanics; however, they may not perfectly mimic wheelchair propulsion over natural surfaces. The goal of this study was to compare kinetic and temporal parameters between propulsion overground on a tile surface and on a dynamometer. Twenty-four experienced manual wheelchair users propelled at a self-selected speed on smooth, level tile and a dynamometer while kinetic data were collected using an instrumented wheel. A Pearson correlation test was used to examine the relationship between propulsion variables obtained on the dynamometer and the overground condition. Ensemble resultant force and moment curves were compared using cross-correlation and qualitative analysis of curve shape. User biomechanics were correlated (R ranging from 0.41 to 0.83) between surfaces. Overall, findings suggest that although the dynamometer does not perfectly emulate overground propulsion, wheelchair users were consistent with the direction and amount of force applied, the time peak force was reached, push angle, and their stroke frequency between conditions. PMID- 22085812 TI - Detailed analysis of specific nail psoriasis features and their correlations with clinical parameters: a cross-sectional study. AB - BACKGROUND: Occurrence rates of specific features of psoriatic nails, as well as the influence of variable clinical parameters on nail involvement in psoriasis, are not determined. OBJECTIVE: To evaluate the frequency and characteristics of nail involvement in patients with psoriasis and determine the relationship between nail psoriasis and clinical parameters (age, gender, family history, clinical type, age of onset, duration, joint involvement). METHODS: 228 psoriatic patients, who had not received any systematic or topical antipsoriatic treatment for at least a year, were consecutively selected to participate in this cross sectional study. RESULTS: 66.7% of patients had nail psoriasis. A logistic regression model showed that none of the clinical covariates were statistically significant in predicting nail psoriasis. CONCLUSION: The majority of psoriatic patients presented nail psoriasis. The most common feature was oil drop. There was a difference in the prevalence of each feature between fingernails and toenails. In correlation with clinical parameters, nail psoriasis evolves independently. PMID- 22085813 TI - Cost-effectiveness of 13-valent pneumococcal conjugate vaccine: Germany, Greece, and The Netherlands. AB - BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV7) had profound public-health impacts and is considered cost-effective and potentially cost saving. Two new PCVs have been launched, a 10-valent vaccine (PCV10) and a 13 valent vaccine (PCV13). We examined public-health and economic impacts of PCV pediatric national immunization programs (NIPs) in Germany, Greece, and the Netherlands. METHODS: A decision-analytic model was developed to estimate the impact of PCV13, PCV7, and 10-valent pneumococcal conjugate vaccine (PCV10) on invasive pneumococcal disease (IPD), pneumonia (PNE), and acute otitis media (AOM). Using epidemiological data, we calculated the cases of IPD, PNE, and AOM, using country-specific incidence, serotype coverage, disease sequelae, mortality, vaccine effectiveness, indirect effects, costs, and utilities. Direct effects for PCV13- and PCV10-covered serotypes were assumed similar to PCV7. PCV13 was assumed to confer an indirect effect, while PCV10 was not. Assumptions were tested in sensitivity analyses. RESULTS: In a NIP, PCV13 was estimated to eliminate 31.7%, 46.4%, and 33.8% of IPD in Germany, Greece, and the Netherlands, respectively. Compared with PCV7 and PCV10, PCV13 was found to be cost-effective or cost saving in all cases when PCV13 indirect effects were included. CONCLUSIONS: Pediatric NIPs with PCV13 in Europe are expected to have dramatic public-health impacts and be cost-effective or cost saving. PMID- 22085814 TI - Prevalence of human metapneumovirus in adults with acute respiratory tract infection in Beijing, China. AB - OBJECTIVE: To evaluate the prevalence and clinical manifestations of human metapneumovirus (hMPV) in immunocompetent Chinese adults with acute respiratory tract infections (ARTIs). METHODS: A reverse transcription PCR (RT-PCR) assay targeting the P gene was developed in this study and used to detect hMPV in nasal and throat swabs collected from 2936 immunocompetent adult patients with ARTIs in Beijing, China between July 2008 and June 2010. RESULTS: Among the 2936 patients studied, 49 (1.7%) were positive for hMPV, of whom 14 (28.6%) were positive for hMPV_A2b, 19 (38.8%) for hMPV_B1, and 16 (32.6%) for hMPV_B2. hMPV_A1 was not detected. An average detection rate of 6.6% was observed in the peak months of the two epidemic seasons studied. The hMPV prevalence was higher in the sampled elderly (>65 years, 3.2%) than in middle aged adults (25-65 years; 2.0%) and teenagers (14-25 years; 0.9%). During the study period, hMPV infections showed a biennial rhythm of seasonality, peaking from November to March in 2008/09 and from March to June in 2010. CONCLUSION: hMPV infection plays an important role in immunocompetent adults in its epidemic season. The demographic and clinical data presented in this study improves our understanding of the pathogenesis and clinical burden of hMPV infection in adults. PMID- 22085815 TI - Identification and expression of immune genes in the flat oyster Ostrea edulis in response to bonamiosis. AB - The European flat Ostrea edulis is highly susceptible to infection by the protozoan Bonamia ostreae and Bonamia exitiosa, intracellular parasites able to survive and proliferate within the oyster haemocytes. The parasite, once phagocytosed by the haemocyte, the main cellular effector of the immune system, appears to have some counter mechanism that turns off the haemocyte's metabolic destructive capacity, so that the parasite survives within the cell. To further understand the molecular basis of the immune response of the flat oyster against the bonamiosis, suppression subtractive hybridization and Q-PCR approaches were combined to identify genes involved in the development of the infection both in early and advanced phases. Four subtractive cDNA libraries were constructed and sequenced, obtaining a high number of ESTs that were seen to be up or down regulated in the infection. A group of ESTs that play a role in the immune response, such as cytokines, stress proteins, eicosanoids, proteins implicated in phagocytosis and cell junction as well as in transcription signalling were identified and their expression was analysed at different infection levels by Q PCR. The results here reported can help to enrich our understanding about the immune response of O. edulis against bonamiosis and improve our knowledge of the immune mechanisms of oysters. PMID- 22085816 TI - Colonic stenting as a bridge to surgery in malignant large-bowel obstruction: a report from two large multinational registries. AB - OBJECTIVES: To date, this is the largest prospective series in patients with malignant colorectal obstruction to evaluate the effectiveness and safety of colonic self-expanding metal stents (SEMSs) as an alternative to emergency surgery. SEMSs allow restoration of bowel transit and careful tumor staging in preparation for elective surgery, hence avoiding the high morbidity and mortality associated with emergency surgery and stoma creation. METHODS: This report is on the SEMS bridge-to-surgery subset enrolled in two multicenter international registries. Patients were treated per standard of practice, with documentation of clinical and procedural success, safety, and surgical outcomes. RESULTS: A total of 182 patients were enrolled with obstructive tumor in the left colon (85%), rectum (11%), or splenic flexure (4%). Of these patients, 86% had localized colorectal cancer without metastasis. Procedural success was 98% (177/181). Clinical success was 94% (141/150). Elective surgery was performed in 150 patients (9 stomas) and emergency surgery in 7 patients for treatment of a complication (3 stomas). The overall complication rate was 7.8% (13/167), including perforation in 3% (5/167), stent migration in 1.2% (2/167), bleeding in 0.6% (1/167), persistent colonic obstruction in 1.8% (3/167), and stent occlusion due to fecal impaction in 1.2% (2/167). One patient died from complications related to surgical management of a perforation. CONCLUSIONS: SEMSs provide an effective bridge to surgery treatment with an acceptable complication rate in patients with acute malignant colonic obstruction, restoring luminal patency and allowing elective surgery with primary anastomosis in most patients. PMID- 22085817 TI - Risk of hepatocellular carcinoma in diabetic patients and risk reduction associated with anti-diabetic therapy: a population-based cohort study. AB - OBJECTIVES: Using population-based representative insurance claims data, the risk of developing hepatocellular carcinoma (HCC) among diabetes mellitus (DM) patients, as well as whether DM medications alter the risk of developing HCC were investigated. METHODS: From the Taiwan National Health Insurance Research Database, 19,349 newly diagnosed DM patients 20 years and older and 77,396 comparison subjects without DM were identified from claims from 2000 to 2005. The incidences of HCC at the end of 2008 and the risks associated with hepatitis B and hepatitis C were determined. Whether metformin and thiazolidinediones reduce the risk of developing HCC was also measured. RESULTS: The incidence of HCC was twice higher in the DM group compared with the non-DM group (21.0 vs. 10.4 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.73 (95% confidence interval (CI)=1.47-2.03) using multivariable Cox proportional hazard regression. Male sex, cirrhosis, hepatitis B, and hepatitis C were significant independent factors that predict HCC, with HRs of 2.32, 8.65, 2.52, and 5.61, respectively. In the stratified analysis, the HR increased to 72.4 (95% CI=42.9-122) among patients with DM, cirrhosis, and hepatitis C. HCC risk reduction was greater for diabetics taking metformin than those taking thiazolidinediones (51 vs. 44% reduction). CONCLUSIONS: Comorbidity with cirrhosis and/or hepatitis appears to be associated with an extremely increased risk of developing HCC among DM patients. These high-risk patients should be closely monitored for HCC. The use of metformin or thiazolidinediones may reduce the risk of developing HCC. PMID- 22085818 TI - Risk of gastroparesis in subjects with type 1 and 2 diabetes in the general population. AB - OBJECTIVES: In patients with diabetes mellitus (DM) and upper gastrointestinal symptoms, a diagnosis of diabetic gastroparesis is often considered, but population-based data on the epidemiology of diabetic gastroparesis are lacking. We aimed to estimate the frequency of and risk factors for gastroparesis among community subjects with DM. METHODS: In this population-based, historical cohort study, the medical records linkage system of the Rochester Epidemiology Project was used to identify 227 Olmsted County, MN residents with type 1 DM in 1995, a random sample of 360 residents with type 2 DM, and an age- and sex-stratified random sample of 639 nondiabetic residents. Using defined diagnostic criteria, we estimated the subsequent risk of developing gastroparesis in each group through 2006. The risk in DM, compared with frequency-matched community controls, was assessed by Cox proportional hazards modeling. RESULTS: The cumulative proportions developing gastroparesis over a 10-year time period were 5.2% in type 1 DM, 1.0% in type 2 DM, and 0.2% in controls. The age- and gender-adjusted hazard ratios (HRs) for gastroparesis (relative to controls) was 33 (95% confidence interval (CI): 4.0, 274) in type 1 DM and 7.5 (95% CI: 0.8, 68) in type 2 DM. The risk of gastroparesis in type 1 DM was significantly greater than in type 2 DM (HR: 4.4 (1.1, 17)). Heartburn (HR: 6.6 (1.7, 25)) at baseline was associated with diabetic gastroparesis in type 1 DM. CONCLUSIONS: Gastroparesis is relatively uncommon in patients with DM, although an increased risk for gastroparesis was observed in type 1 DM. PMID- 22085819 TI - Gastrointestinal and psychological mediators of health-related quality of life in IBS and IBD: a structural equation modeling analysis. AB - OBJECTIVES: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are chronic gastrointestinal (GI) syndromes in which both GI and psychological symptoms have been shown to negatively impact health-related quality of life (HRQOL). The objective of this study was to use structural equation modeling (SEM) to characterize the interrelationships among HRQOL, GI, and psychological symptoms to improve our understanding of the illness processes in both conditions. METHODS: Study participants included 564 Rome positive IBS patients and 126 IBD patients diagnosed via endoscopic and/or tissue confirmation. All patients completed questionnaires to assess bowel symptoms, psychological symptoms (SCL-90R), and HRQOL (SF-36). SEM with its two components of confirmatory analyses and structural modeling were applied to determine the relationships between GI and psychological symptoms and HRQOL within the IBS and IBD groups. RESULTS: For both IBD and IBS, psychological distress was found to have a stronger direct effect on HRQOL (-0.51 and -0.48 for IBS and IBD, respectively) than GI symptoms (-0.25 and -0.28). The impact of GI symptoms on psychological distress was stronger in IBD compared with IBS (0.43 vs. 0.22; P<0.05). The indirect effect of GI symptoms on HRQOL operating through psychological distress was significantly higher in IBD than IBS (-0.21 vs. -0.11; P<0.05). CONCLUSIONS: Psychological distress is less dependent on GI symptom severity in IBS compared with IBD even though the degree that psychological distress impacts HRQOL is similar. The findings emphasize the importance of addressing psychological symptoms in both syndromes. PMID- 22085820 TI - Fecal incontinence in systemic sclerosis is secondary to neuropathy. AB - OBJECTIVES: Systemic sclerosis (SSc) is a chronic multi-system autoimmune disorder with gastrointestinal tract (GIT) involvement in up to 90% of patients and anorectal involvement occurs in up to 50% of patients. The pathogenesis of gastrointestinal abnormalities may be both myogenic and neurogenic. We aimed to identify which anorectal physiological abnormalities correlate with clinical symptoms and thus understand the pathophysiology of anorectal involvement in SSc. METHODS: In total, 44 SSc patients (24 symptomatic (Sx) (fecal incontinence) and 20 asymptomatic (ASx)) and 20 incontinent controls (ICs) were studied. Patients underwent anorectal manometry, rectal mucosal blood flow (RMBF), rectal compliance (barostat), and rectoanal inhibitory reflex assessment (RAIR). RESULTS: Anal squeeze pressure was lower in the IC group compared with both the ASx and Sx groups (IC: 46.95 (30-63.9)) vs. ASx: 104.6 (81-128.3) vs. (Sx: 121.4 (101.3-141.6); P < 0.05). Resting pressure was lower in the IC group. RMBF and rectal compliance did not differ between groups. Anal, but not rectal, sensory threshold, was significantly attenuated in Sx patients (Sx: 10.4 (8.8-11.4) vs. ASx: 6.7 (5.7-7.7) vs. IC: 8.5 (6.5-10.4); P < 0.05). There was a positive correlation between anal sensory thresholds and incontinence score in SSc patients (r = 0.54; P < 0.05). RAIR was absent in 11/24 Sx patients but only in 2/20 ASx and in 1/20 IC patients. CONCLUSIONS: Fecal incontinence in SSc is related to neuropathy as suggested by absent RAIR and higher anal sensory threshold and is related less so to sphincter atrophy and rectal fibrosis. PMID- 22085821 TI - The effects of food shortage during larval development on adult body size, body mass, physiology and developmental time in a tropical damselfly. AB - Few studies have looked jointly at the effects of larval stressors on life history and physiology across metamorphosis, especially in tropical insects. Here we investigated how the variation of food availability during the larval stage of the tropical and territorial American rubyspot damselfly (Hetaerina americana) affects adult body size and body mass, and two physiological indicators of condition--phenoloxidase activity (an indicator of immune ability) and protein concentration. We also investigated whether larval developmental time is prolonged when food is scarce, an expected situation for tropical species whose larval time is less constrained, compared to temperate species. Second instar larvae were collected from their natural environments and reared in one of two diet regimes: (i) "rich" provided with five Artemia salina prey every day, and (ii) "poor" provided with two A. salina prey every day. In order to compare how distinct our treatments were from natural conditions, a second set of last-instar larvae were also collected and allowed to emerge. Only body size and phenoloxidase increased in the rich regime, possibly to prioritize investment on sexually selected traits (which increase mating opportunities), and immune ability, given pathogen pressure. The sexes did not differ in body size in relation to food regimes but they did differ in body mass and protein concentration; this can be explained on the basis of the energetically demanding territorial activities by males (for the case of body mass), and female allocation to egg production (for the case of protein). Finally, animals delayed larval development when food was scarce, which is coherent for tropical environments. These findings provide key insights in the role of food availability in a tropical species. PMID- 22085822 TI - Using the underlying biological organization of the Mycobacterium tuberculosis functional network for protein function prediction. AB - Despite ever-increasing amounts of sequence and functional genomics data, there is still a deficiency of functional annotation for many newly sequenced proteins. For Mycobacterium tuberculosis (MTB), more than half of its genome is still uncharacterized, which hampers the search for new drug targets within the bacterial pathogen and limits our understanding of its pathogenicity. As for many other genomes, the annotations of proteins in the MTB proteome were generally inferred from sequence homology, which is effective but its applicability has limitations. We have carried out large-scale biological data integration to produce an MTB protein functional interaction network. Protein functional relationships were extracted from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and additional functional interactions from microarray, sequence and protein signature data. The confidence level of protein relationships in the additional functional interaction data was evaluated using a dynamic data-driven scoring system. This functional network has been used to predict functions of uncharacterized proteins using Gene Ontology (GO) terms, and the semantic similarity between these terms measured using a state-of-the-art GO similarity metric. To achieve better trade-off between improvement of quality, genomic coverage and scalability, this prediction is done by observing the key principles driving the biological organization of the functional network. This study yields a new functionally characterized MTB strain CDC1551 proteome, consisting of 3804 and 3698 proteins out of 4195 with annotations in terms of the biological process and molecular function ontologies, respectively. These data can contribute to research into the Development of effective anti-tubercular drugs with novel biological mechanisms of action. PMID- 22085823 TI - Variation in number of cagA EPIYA-C phosphorylation motifs between cultured Helicobacter pylori and biopsy strain DNA. AB - The Helicobacter pylori cagA gene encodes a cytotoxin which is activated by phosphorylation after entering the host epithelial cell. Phosphorylation occurs on specific tyrosine residues within EPIYA motifs in the variable 3'-region. Four different cagA EPIYA motifs have been defined according to the surrounding amino acid sequence; EPIYA-A, -B, -C and -D. Commonly, EPIYA-A and -B are followed by one or more EPIYA-C or -D motif. Due to observed discrepancies in cagA genotypes in cultured H. pylori and the corresponding DNA extracts it has been suggested that genotyping assays preferentially should be performed directly on DNA isolated from biopsy specimens. Gastric biopsies randomly selected from a Swedish cohort were homogenised and used for both direct DNA isolation and for H. pylori specific culturing and subsequent DNA isolation. In 123 of 153 biopsy specimens, the cagA EPIYA genotypes were in agreement with the corresponding cultured H. pylori strains. A higher proportion of mixed cagA EPIYA genotypes were found in the remaining 30 biopsy specimens. Cloning and sequencing of selected cagA EPIYA amplicons revealed variations in number of cagA EPIYA-C motifs in the mixed amplicons. The study demonstrates that culturing of H. pylori introduces a bias in the number of EPIYA-C motif. Consistent with other H. pylori virulence genotyping studies, we suggest that cagA EPIYA analysis should be performed using total DNA isolated from biopsy specimens. PMID- 22085824 TI - Effect of gonadotropin-releasing hormone on phagocytic leucocytes of rainbow trout. AB - To clarify the role of gonadotropin-releasing hormone (GnRH) in the fish immune system, in vitro effect of GnRH was examined in phagocytic leucocytes of rainbow trout (Oncorhynchus mykiss). Gene expression of GnRH-receptor was detected by RT PCR in leucocytes from head kidney. Administration of sGnRH increased proliferation and mRNA levels of a proinflammatory cytokine, tumor necrosis factor (TNF)-alpha, in trout leucocytes. Superoxide production in zymosan stimulated phagocytic leucocytes was also increased by sGnRH in a dose-related manner from 0.01 to 100 nM. There was no significant effect of sGnRH on mRNA levels of growth hormone (GH) expressed in trout phagocytic leucocytes. Immunoneutralization of GH by addition of anti-salmon GH serum into the medium could not block the stimulatory effect of sGnRH on superoxide production. These results indicate that GnRH stimulates phagocytosis in fish leucocytes through a GnRH-receptor-dependent pathway, and that the effect of GnRH is not mediated through paracrine GH in leucocytes. PMID- 22085825 TI - Adipokinetic hormone-induced antioxidant response in Spodoptera littoralis. AB - The antioxidative potential of the Manduca sexta adipokinetic hormone (Manse-AKH) in the last instar larvae of Spodoptera littoralis (Noctuidae, Lepidoptera) was demonstrated after exposure to oxidative stress (OS) elicited by feeding on artificial diet containing tannic acid (TA). Determination of protein carbonyls (PCs) and reduced glutathione (GSH) levels, monitoring of activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferases (GSTs), as well as measuring of the mRNA expression of CAT and SOD were used as markers of the OS. Injection of the Manse-AKH (5 pmol per individual) reversed the OS status by mitigation of PCs formation and by stimulation of glutathione-S transferases (GSTs) activity. The CAT and SOD mRNA expression was significantly suppressed after the Manse-AKH injection while activity of these enzymes was not affected. These results indicate that diminishing of OS after the AKH injection might be a result of activation of specific enzymatic pathway possibly at the post-translational level rather than a direct effect on regulation of antioxidant marker genes at the transcriptional level. PMID- 22085826 TI - The influence of social capital and socio-economic conditions on self-rated health among residents of an economically and health-deprived South African township. AB - BACKGROUND: Surprisingly few studies have investigated the interplay of multiple factors affecting self-rated health outcomes and the role of social capital on health in developing countries, a prerequisite to strengthening our understanding of the influence of social and economic conditions on health and the most effective aid. Our study aimed to identify social and economic conditions for health among residents of an economically and health-deprived community. METHODS: Data were gathered through a survey administered to respondents from 1,020 households in Grahamstown a suburb in the Eastern Cape, South Africa (response rate 97.9%). We investigated the influence of social and economic conditions (education, employment, income, social capital, housing quality and neighborhood quality) on self-rated health. We used ordinal logistic regression analyses to identify the relationship of these conditions and self-rated health. RESULTS: Our study found that education and social capital positively correlated with health; unemployment, poor educational level and advanced age negatively correlated. We found no significant correlations between self-rated health and housing quality, neighbourhood quality, income, gender, or marital status. CONCLUSION: We highlight the possible impacts of social capital, employment, and education on health, and suggest that health outcomes may be improved through interventions beyond the health system: creating job opportunities, strengthening social capital, bettering educational systems, and promoting educational access. Policymakers should consider the benefits of such programmes when addressing health outcomes in financially distressed districts. PMID- 22085827 TI - Hepatic mitochondrial dysfunction in Friedreich ataxia. AB - BACKGROUND: Mitochondrial dysfunction due to respiratory chain impairment is a key feature in pathogenesis of Friedreich ataxia. Friedreich ataxia affects the nervous system, heart and pancreas. METHODS: We assessed hepatic mitochondrial function by (13)C-methionine-breath-test in 16 Friedreich ataxia patients and matched healthy controls. RESULTS: Patients exhaled significantly smaller amounts of (13)CO(2) over 90 minutes. Maximal exhaled percentage dose of (13)CO(2) recovery was reduced compared to controls. CONCLUSIONS: (13)C-methionine-breath test indicates subclinical hepatic mitochondrial dysfunction in Friedreich ataxia but did not correlate with GAA repeat lengths, disease duration or disease severity. PMID- 22085828 TI - Reduced prepulse inhibition as an early vulnerability marker of the psychosis prodrome in adolescence. AB - BACKGROUND: The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing and nature of these changes have not been established. The aim of the present study was to determine whether three "classic" neurophysiological markers of schizophrenia are also characteristic of young adolescents (12-18 years) at ultra-high risk for psychosis (UHR). METHODS: 63 young UHR individuals and 68 typically developing, age-, sex- and IQ-matched controls were recruited for neurophysiological assessment. Data for P50 suppression, prepulse inhibition (PPI) and smooth pursuit eye movements (SPEM) were gathered and compared. RESULTS: UHR individuals showed reduced PPI compared to controls, which became more pronounced when controls were directly compared to medication-naive UHR individuals (N=39). There were no group differences in P50 or SPEM measures. CONCLUSIONS: These results suggest that PPI is a relatively early vulnerability marker, while changes in other neurophysiological measures may only be detected or affected later during the illness course. Antipsychotic and antidepressant medication may aid in elevating PPI levels and potentially have a neuroprotective effect. PMID- 22085829 TI - Parameterization of multiple Bragg curves for scanning proton beams using simultaneous fitting of multiple curves. AB - Although Bortfeld's analytical formula is useful for describing Bragg curves, measured data can deviate from the values predicted by the model. Thus, we sought to determine the parameters of a closed analytical expression of multiple Bragg curves for scanning proton pencil beams using a simultaneous optimization algorithm and to determine the minimum number of energies that need to be measured in treatment planning so that complete Bragg curves required by the treatment planning system (TPS) can be accurately predicted. We modified Bortfeld's original analytical expression of Bragg curves to accurately describe the dose deposition resulting from secondary particles. The parameters of the modified analytical expression were expressed as the parabolic cylinder function of the ranges of the proton pencil beams in water. Thirty-nine discrete Bragg curves were measured in our center using a PTW Bragg Peak chamber during acceptance and commission of the scanning beam proton delivery system. The coefficients of parabolic function were fitted by applying a simultaneous optimization algorithm to seven measured curves. The required Bragg curves for 45 energies in the TPS were calculated using our parameterized analytical expression. Finally, the 10 cm width of spread-out Bragg peaks (SOBPs) of beams with maximum energies of 221.8 and 121.2 MeV were then calculated in the TPS and compared with measured data. Compared with Bortfeld's original formula, our modified formula improved fitting of the measured depth dose curves at depths around three-quarters of the maximum range and in the beam entrance region. The parabolic function described the relationship between the parameters of the analytic expression of different energies. The predicted Bragg curves based on the parameters fitted using the seven measured curves accurately described the Bragg curves of proton pencil beams of 45 energies configured in our TPS. When we used the calculated Bragg curves as the input to TPS, the standard deviations of the measured and calculated data points along the 10 cm SOBPs created with proton pencil beams with maximum energies of 221.8 and 121.2 MeV were 1.19% and 1.18%, respectively, using curves predicted by the algorithm generated from the seven measured curves. Our method would be a valuable tool to analyze measured Bragg curves without the need for time-consuming measurements and correctly describe multiple Bragg curves using a closed analytical expression. PMID- 22085830 TI - Kinetics and DFT studies on water oxidation by Ce4+ catalyzed by [Ru(terpy)(bpy)(OH2)]2+. AB - The Ru(V)==O species and other intermediates in O(2) evolution from water catalyzed by [Ru(terpy)(bpy)(OH(2))](2+) were spectrophotometrically characterized, and the spectral components observed were identified based on the TD-DFT calculations. Moreover, important insights into the rapid paths after the RDS were given by the DFT studies. PMID- 22085831 TI - Modifying protein adsorption by layers of glutathione pre-adsorbed on Au(111). AB - Molecular interaction with metal surfaces raises fundamental questions regarding their binding tendency, their dispersion on the surface, as well as their conformation which may change their biological properties; addressing these questions, and being able to tune protein interactions, is of primary importance for the control of biointerfaces. In this study, one tripeptide, GSH (glu-cys gly), was used to condition gold surfaces and thus influence the adsorption of bovine serum albumin (BSA). Depending on the pH value of the GSH solution, cationic, zwitterionic or anionic forms of the tripeptide could be stabilised on the surface, before interacting with BSA solutions. The amount of proteins was observed to depend both on the chemical state of the adsorbed underlying peptide and on the solvent of the protein solution, indicating an important role of electrostatic interactions upon protein adsorption. Moreover, atomic force microscopy (AFM), and synchrotron IR microscopy revealed a heterogeneous distribution of proteins on the GSH layer. PMID- 22085832 TI - Nuclear receptor HNF4alpha binding sequences are widespread in Alu repeats. AB - BACKGROUND: Alu repeats, which account for ~10% of the human genome, were originally considered to be junk DNA. Recent studies, however, suggest that they may contain transcription factor binding sites and hence possibly play a role in regulating gene expression. RESULTS: Here, we show that binding sites for a highly conserved member of the nuclear receptor superfamily of ligand-dependent transcription factors, hepatocyte nuclear factor 4alpha (HNF4alpha, NR2A1), are highly prevalent in Alu repeats. We employ high throughput protein binding microarrays (PBMs) to show that HNF4alpha binds > 66 unique sequences in Alu repeats that are present in ~1.2 million locations in the human genome. We use chromatin immunoprecipitation (ChIP) to demonstrate that HNF4alpha binds Alu elements in the promoters of target genes (ABCC3, APOA4, APOM, ATPIF1, CANX, FEMT1A, GSTM4, IL32, IP6K2, PRLR, PRODH2, SOCS2, TTR) and luciferase assays to show that at least some of those Alu elements can modulate HNF4alpha-mediated transactivation in vivo (APOM, PRODH2, TTR, APOA4). HNF4alpha-Alu elements are enriched in promoters of genes involved in RNA processing and a sizeable fraction are in regions of accessible chromatin. Comparative genomics analysis suggests that there may have been a gain in HNF4alpha binding sites in Alu elements during evolution and that non Alu repeats, such as Tiggers, also contain HNF4alpha sites. CONCLUSIONS: Our findings suggest that HNF4alpha, in addition to regulating gene expression via high affinity binding sites, may also modulate transcription via low affinity sites in Alu repeats. PMID- 22085833 TI - Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation. AB - Galantamine is a drug currently used to treat Alzheimer's disease (AD); in this group of patients it has been observed that concomitant ischemic brain injury can accelerate their cognitive deficit. We have previously shown that galantamine can afford neuroprotection on in vitro and in vivo models related to brain ischemia. In this context, this study was planned to investigate the intracellular signaling pathways implicated in the protective effect of galantamine on an in vitro brain ischemia-reperfusion model, namely rat hippocampal slices subjected to oxygen and glucose deprivation (OGD) followed by reoxygenation. Galantamine protected hippocampal slices subjected to OGD in a concentration-dependent manner; at 15 MUM, cell death was reduced to almost control levels. The neuroprotective effects of galantamine were reverted by mecamylamine and AG490, but not by atropine, indicating that nicotinic receptors and Jak2 participated in this action. Galantamine also prevented p65 translocation into the nucleus induced by OGD; this effect was also linked to nicotinic receptors and Jak2. Furthermore, galantamine reduced iNOS induction and production of NO caused by OGD via Jak2. ROS production by NADPH oxidase (NOX) activation was also inhibited by galantamine. In conclusion, galantamine afforded neuroprotection under OGD reoxygenation conditions by activating a signaling pathway that involves nicotinic receptors, Jak2 and the consequent inhibition of NOX and NFkappaB/iNOS. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22085834 TI - Age-dependent changes in temperature regulation - a mini review. AB - It is now well recognized that the body temperature of older men and women is lower than that of younger people and that their tolerance of thermal extremes is more limited. The regulation of body temperature does not depend on a single organ, but rather involves almost all the systems of the body, i.e. systems not exclusively dedicated to thermoregulatory functions such as the cardiovascular and respiratory systems. Since these deteriorate naturally with advancing age, the decrement in their functions resonates throughout all the bodily processes, including those that control body temperature. To the extent that the age-related changes in some of these, e.g. in the musculoskeletal system, can be slowed, or even prevented, by certain measures, e.g. fitness training, so can the decrements in thermoregulatory functions. Some deficits, however, are unavoidable, e.g. structural skin changes and metabolic alterations. These impact directly on the ability of the elderly to maintain thermal homeostasis, particularly when challenged by ambient thermal extremes. Since the maintenance of a relatively stable, optimal core temperature is one of the body's most important activities, its very survival can be threatened by these disorders. The present article describes the principal, age-associated changes in physiological functions that could affect the ability of seniors to maintain their body temperature when exposed to hot or cold environments. PMID- 22085835 TI - A fully implanted programmable stimulator based on wireless communication for epidural spinal cord stimulation in rats. AB - Clinical research indicates that the epidural spinal cord stimulation (ESCS) has shown potential in promoting locomotor recovery in patients with incomplete spinal cord injury (ISCI). This paper presents the development of a fully implantable voltage-regulated stimulator with bi-directional wireless communication for investigating underlying neural mechanisms of ESCS facilitating motor function improvement. The stimulation system consists of a computer, an external controller, an implantable pulse generator (IPG), a magnet, the extension leads and a stimulation electrode. The telemetry transmission between the IPG and the external controller is achieved by a commercially available transceiver chip with 2.4GHz carrier band. The magnet is used to activate the IPG only when necessary to minimize the power consumption. The encapsulated IPG measures 33mm*24mm*8mm, with a total mass of ~12.6g. Feasibility experiments are conducted in three Sprague-Dawley rats to validate the function of the stimulator, and to investigate the relationship between lumbar-sacral ESCS and hindlimb electromyography (EMG) responses. The results show that the stimulation system provides an effective tool for investigation of ESCS application in motor function recovery in small animals. PMID- 22085836 TI - Comparison of within hive sampling and seasonal activity of Nosema ceranae in honey bee colonies. AB - Nosema ceranae is a microsporidian parasite of the European honey bee, Apis mellifera, that is found worldwide and in multiple Apis spp.; however, little is known about the effects of N. ceranae on A. mellifera. Previous studies using spore counts suggest that there is no longer a seasonal cycle for N. ceranae and that it is found year round with little variation in infection intensity among months. Our goal was to determine whether infection levels differ in bees collected from different areas of the hive and if there may be seasonal differences in N. ceranae infections. A multiplex species-specific real-time PCR assay was used for the detection and quantification of N. ceranae. Colonies were sampled monthly from September 2009-2010 by collecting workers from honey supers, the fringe of the brood nest, and the brood nest. We found that all bees sampled were infected with N. ceranae and that there was no significant difference in infection levels among the different groups of bees sampled (P=0.74). However, significant differences in colony infection levels were found at different times of the year (P<0.01) with the highest levels in April-June and lower levels in the fall and winter. While our study was only performed for one year, it sheds light on the fact that there may be a seasonality to N. ceranae infections. Being able to predict future N. ceranae infections can be used to better advise beekeepers on N. ceranae management. PMID- 22085838 TI - Relating temperature dependence of atom scattering spectra to surface corrugation. AB - It is suggested that a measurement of the temperature dependence of the most probable intensity of energy-resolved atom-surface scattering spectra can reveal the strength of the surface corrugation. To support this conjecture, a classical mechanical theory of atom scattering from a corrugated surface, valid in the weak corrugation limit, is developed. The general result for the scattering probability is expressed in terms of spatial integrals over the impact parameter within a surface unit cell. For the case of a one-dimensional corrugation, approximate expressions for the scattering probability are obtained in terms of analytic closed form expressions. As an indicator of its relation to experimental measurements, calculations using a one-dimensional corrugation model are compared with data for Ar scattering from a molten Ga surface and an approximate value of the corrugation height parameter is extracted. PMID- 22085837 TI - Characterizing the interface between wild ducks and poultry to evaluate the potential of transmission of avian pathogens. AB - BACKGROUND: Characterizing the interface between wild and domestic animal populations is increasingly recognized as essential in the context of emerging infectious diseases (EIDs) that are transmitted by wildlife. More specifically, the spatial and temporal distribution of contact rates between wild and domestic hosts is a key parameter for modeling EIDs transmission dynamics. We integrated satellite telemetry, remote sensing and ground-based surveys to evaluate the spatio-temporal dynamics of indirect contacts between wild and domestic birds to estimate the risk that avian pathogens such as avian influenza and Newcastle viruses will be transmitted between wildlife to poultry. We monitored comb ducks (Sarkidiornis melanotos melanotos) with satellite transmitters for seven months in an extensive Afro-tropical wetland (the Inner Niger Delta) in Mali and characterise the spatial distribution of backyard poultry in villages. We modelled the spatial distribution of wild ducks using 250-meter spatial resolution and 8-days temporal resolution remotely-sensed environmental indicators based on a Maxent niche modelling method. RESULTS: Our results show a strong seasonal variation in potential contact rate between wild ducks and poultry. We found that the exposure of poultry to wild birds was greatest at the end of the dry season and the beginning of the rainy season, when comb ducks disperse from natural water bodies to irrigated areas near villages. CONCLUSIONS: Our study provides at a local scale a quantitative evidence of the seasonal variability of contact rate between wild and domestic bird populations. It illustrates a GIS-based methodology for estimating epidemiological contact rates at the wildlife and livestock interface integrating high-resolution satellite telemetry and remote sensing data. PMID- 22085839 TI - Synergistic effect between BRAP polymorphism and diabetes on the extent of coronary atherosclerosis in the Chinese population. AB - OBJECTIVES: Coronary artery disease (CAD) is a multifactorial disease and influenced by genetics. We previously reported that a single nucleotide polymorphism (rs11066001) in the BRAP gene was related to the risk of myocardial infarction. However, it is unclear whether rs11066001 is associated with the extent of coronary atherosclerosis. METHODS: We enrolled 732 patients scheduled for diagnostic coronary angiography. Angiographic presence of significant CAD (0 or 1), clinical vessel score (CVS, 0-3 vessels) and diffuse score (DS, 0-11.5) were used to evaluate the extent of coronary atherosclerosis. Genotyping was carried out by the TaqMan technology. RESULTS: Of all patients, 558 (76.2%) had significant CAD. The odds ratio for the GG to the AA genotype was 2.45 (95% CI 1.13-5.34, p = 0.024) for the presence of significant CAD. The CVS was correlated with the frequency of genotypes in the recessive model (p = 0.001). Regression analysis showed a significant association between rs11066001 and the presence of significant CAD and DS (all p < 0.05). There was a synergistic effect between rs11066001 and diabetes on the occurrence of significant CAD (p < 0.001 for interaction). CONCLUSION: The BRAP rs11066001 gene is associated with the extent of coronary atherosclerosis and has a synergistic effect with diabetes on the occurrence of significant CAD in the Chinese population. PMID- 22085840 TI - The evaluation of knee bone mineral density following open-wedge high tibial osteotomy. AB - Examinations of bone density changes in selected knee bone ends were evaluated prospectively in a randomized group of 28 patients, aged from 41 to 65 (mean: 55.3 years), who had varus deformations of their mechanic limb axes, mean 8 degrees. The examinations were conducted during the preoperative period, 10 days, 3, 6, and 12 weeks, as well as 6 and 12 months after the procedure. A statistically significant increase in bone density was observed in the medial tibial condyle area, while a statistically insignificant decrease of bone density was noted in the medial femoral condyles. Bone density increased in the lateral tibial condyle area, whereas there were no density changes in the area of the lateral femoral condyles. The research results demonstrate that the relief achieved in ailments after high tibial osteotomies does not directly correspond to the bone density of the affected areas. PMID- 22085841 TI - Associations between cerebral and systemic endothelial function in migraine patients: a post-hoc study. AB - BACKGROUND: There is a growing interest in the role of the endothelium in migraine. Recently, our group showed differences in endothelial function between the anterior and posterior cerebral circulation in healthy subjects, reduced vasodilatatory capacity of the posterior cerebral circulation and unimpaired systemic endothelial function in migraine patients without comorbidities. However, the relationship between cerebral and systemic endothelial function and the anterior and posterior cerebral endothelial function in migraine patients is still not clear. METHODS: We compared cerebral and systemic endothelial function through post-hoc linear regression analysis of cerebrovascular reactivity (CVR) to L-arginine between the middle cerebral artery (MCA) and flow-mediated vasodilatation (FMD) of the right brachial artery and the posterior cerebral artery (PCA) and FMD in migraine patients without comorbidities and in healthy subjects. The anterior and posterior cerebral endothelial function was also compared using post-hoc linear regression analysis between CVR to L-arginine in the MCA and the PCA. RESULTS: No significant correlation was found between CVR to L-arginine in the MCA and FMD and in the PCA and FMD in migraine patients with aura (p = 0.880 vs. p = 0.682), without aura (p = 0.153 vs. p = 0.179) and in healthy subjects (p = 0.869 vs. p = 0.662). On the other hand, we found a significant correlation between CVR to L-arginine in the MCA and PCA in migraine patients with aura (p = 0.004), without aura (p = 0.001) and in healthy subjects (p = 0.002). Detailed analysis of the linear regression between all migraine patients and healthy subjects did not show any difference in the regression coefficient (slope) (p = 0.382). However, a significant difference in curve elevation (intercept) was found (p = 0.002). CONCLUSIONS: Our study suggests that the endothelial function in the cerebral and systemic circulation might be different in migraine patients without comorbidities, while that of the anterior and posterior cerebral circulation might be coupled. These results could improve understanding of endothelial function in migraine patients without comorbidities. PMID- 22085842 TI - Investigation of urinary volatile organic metabolites as potential cancer biomarkers by solid-phase microextraction in combination with gas chromatography mass spectrometry. AB - BACKGROUND: Non-invasive diagnostic strategies aimed at identifying biomarkers of cancer are of great interest for early cancer detection. Urine is potentially a rich source of volatile organic metabolites (VOMs) that can be used as potential cancer biomarkers. Our aim was to develop a generally reliable, rapid, sensitive, and robust analytical method for screening large numbers of urine samples, resulting in a broad spectrum of native VOMs, as a tool to evaluate the potential of these metabolites in the early diagnosis of cancer. METHODS: To investigate urinary volatile metabolites as potential cancer biomarkers, urine samples from 33 cancer patients (oncological group: 14 leukaemia, 12 colorectal and 7 lymphoma) and 21 healthy (control group, cancer-free) individuals were qualitatively and quantitatively analysed. Dynamic solid-phase microextraction in headspace mode (dHS-SPME) using a carboxen-polydimethylsiloxane (CAR/PDMS) sorbent in combination with GC-qMS-based metabolomics was applied to isolate and identify the volatile metabolites. This method provides a potential non-invasive method for early cancer diagnosis as a first approach. To fulfil this objective, three important dHS-SPME experimental parameters that influence extraction efficiency (fibre coating, extraction time and temperature of sampling) were optimised using a univariate optimisation design. The highest extraction efficiency was obtained when sampling was performed at 50 degrees C for 60 min using samples with high ionic strengths (17% sodium chloride, w v(-1)) and under agitation. RESULTS: A total of 82 volatile metabolites belonging to distinct chemical classes were identified in the control and oncological groups. Benzene derivatives, terpenoids and phenols were the most common classes for the oncological group, whereas ketones and sulphur compounds were the main classes that were isolated from the urine headspace of healthy subjects. The results demonstrate that compound concentrations were dramatically different between cancer patients and healthy volunteers. The positive rates of 16 patients among the 82 identified were found to be statistically different (P<0.05). A significant increase in the peak area of 2-methyl-3-phenyl-2-propenal, p-cymene, anisole, 4-methyl-phenol and 1,2-dihydro-1,1,6-trimethyl-naphthalene in cancer patients was observed. On average, statistically significant lower abundances of dimethyl disulphide were found in cancer patients. CONCLUSIONS: Gas chromatographic peak areas were submitted to multivariate analysis (principal component analysis and supervised linear discriminant analysis) to visualise clusters within cases and to detect the volatile metabolites that are able to differentiate cancer patients from healthy individuals. Very good discrimination within cancer groups and between cancer and control groups was achieved. PMID- 22085843 TI - Involvement of oxidative stress-induced ERK/JNK activation in the Cu(2+)/pyrrolidine dithiocarbamate complex-triggered mitochondria-regulated apoptosis in pancreatic beta-cells. AB - Oxidative stress was demonstrated to promote the progression of diabetes mellitus (DM). It has been suggested that copper may play a specific role in the progression and pathogenesis of DM. Pyrrolidine dithiocarbamate (PDTC), a widely apply to the medicine, was known to be capable of enhancing copper accumulation. In this study, we investigated the effect of submicromolar-concentration Cu(2+)/PDTC complex on pancreatic beta-cell damage and evaluated the role of oxidative stress in this effect. CuCl(2) (0.01-300MUM) did not affect the cell viability in beta-cell line RIN-m5F cells. However, combination of CuCl(2) (0.5MUM) and PDTC (0.3MUM) markedly reduced RIN-m5F cell viability. Cu(2+)/PDTC complex could also increase the LPO and decrease the intracellular reduced GSH levels, and display several features of apoptosis signals including: increase in sub-G1 cell population, annexin-V binding, and caspase-3 activity, mitochondrial dysfunctions, and the activation of PARP and caspase cascades, which accompanied with the marked increase the intracellular Cu(2+) levels. These apoptotic-related responses of Cu(2+)/PDTC complex-induced could be effectively prevented by antioxidant N-acetylcysteine (NAC). Furthermore, Cu(2+)/PDTC complex was capable of increasing the phosphorylations of ERK1/2 and JNK, and its upstream kinase MEK1/2 and MKK4, which could be reversed by NAC. Transfection with ERK2- and JNK specific si-RNA and specific inhibitors SP600125 and PD98059 could inhibit ERK1/2 and JNK activation and attenuate MMP loss and caspase-3 activity induced by the Cu(2+)/PDTC complex. Taken together, these results are the first report to demonstrate that the Cu(2+)/PDTC complex triggers a mitochondria-regulated apoptosis via an oxidative stress-induced ERK/JNK activation-related pathway in pancreatic beta-cells. PMID- 22085844 TI - Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT. AB - Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA (p=0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA negative subjects (p=0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease. PMID- 22085845 TI - Inhibition of TNF-alpha stimulated nuclear factor-kappa B (NF-kappaB) activation by cyclometalated platinum(II) complexes. AB - Cyclometalated platinum(II) complexes [Pt(II)(C^N^N)(C=NR)](+) (HC^N^N = 6-phenyl 2,2'-bipyridyl) display significant inhibition towards TNF-alpha stimulated NF kappaB-dependent gene transcription at concentrations down to the micromolar range. PMID- 22085846 TI - Membrane trafficking and signaling: two sides of the same coin. AB - Recent findings on clathrin-dependent and non clathrin-dependent endocytic routes are currently changing our classical view of endocytosis. Originally seen as a way for the cell to internalize membrane, receptors or various soluble molecules, this process is in fact directly linked to complex signaling pathways. Here, we review new insights in endocytosis and present latest development in imaging techniques that allow us to visualize and follow the dynamics of membrane associated signaling events at the plasma membrane and other intracellular compartments. The immune synapse is taken as an illustration of the importance of membrane reorganization and proteins clustering to initiate and maintain signaling. Future challenges include understanding the crosslink between traffic and signaling and how all compartmentalized signals are integrated inside the cell at a higher level. PMID- 22085847 TI - Zalpha-domains: at the intersection between RNA editing and innate immunity. AB - The involvement of A to I RNA editing in antiviral responses was first indicated by the observation of genomic hyper-mutation for several RNA viruses in the course of persistent infections. However, in only a few cases an antiviral role was ever demonstrated and surprisingly, it turns out that ADARs - the RNA editing enzymes - may have a prominent pro-viral role through the modulation/down regulation of the interferon response. A key role in this regulatory function of RNA editing is played by ADAR1, an interferon inducible RNA editing enzyme. A distinguishing feature of ADAR1, when compared with other ADARs, is the presence of a Z-DNA binding domain, Zalpha. Since the initial discovery of the specific and high affinity binding of Zalpha to CpG repeats in a left-handed helical conformation, other proteins, all related to the interferon response pathway, were shown to have similar domains throughout the vertebrate lineage. What is the biological function of this domain family remains unclear but a significant body of work provides pieces of a puzzle that points to an important role of Zalpha domains in the recognition of foreign nucleic acids in the cytoplasm by the innate immune system. Here we will provide an overview of our knowledge on ADAR1 function in interferon response with emphasis on Zalpha domains. PMID- 22085848 TI - Tiarellic acid attenuates airway hyperresponsiveness and inflammation in a murine model of allergic asthma. AB - Asthma is a persistent inflammatory disease characterized by airway obstruction and hyperresponsiveness in association with airway inflammation. In the current research, we studied the anti-inflammatory and anti-asthmatic effects of tiarellic acid (TA) isolated from Tiarella polyphylla, based on asthmatic parameters, such as immunoglobulin E (IgE) level, cytokine release, eosinophilia, airway hyperresponsiveness (AHR), reactive oxygen species (ROS) and mucus hypersecretion, in an ovalbumin (OVA)-sensitized/challenged mouse model. TA significantly inhibited increases in IgE, levels of ROS and T helper cytokines, such as interleukin (IL)-4, IL-5, TNF-alpha, and IL-13, in bronchoalveolar lavage fluid (BALF), and effectively suppressed airway hyperresponsiveness, eosinophilia, and mucus hypersecretion in the asthmatic mouse model. In addition, we found that administration of TA attenuated ovalbumin-induced increases in NF kappaB activity in lungs. The efficacy of TA was comparable to that of montelukast, a currently available anti-asthmatic drug. Our results support the utility of TA as a herbal medicine for asthma treatment and may have application in the development of anti-inflammatory and anti-asthmatic drugs. PMID- 22085852 TI - Antiviral immunity. Viral restriction goes nuclear. PMID- 22085849 TI - Fungal physiology. Ustilago takes control. AB - Ustilago maydis Cmu1 is a virulence factor that can move through plant cells, redirecting plant metabolic pathways to favour fungal infection. PMID- 22085857 TI - Bacterial physiology. Seeing Caulobacter in 3D. PMID- 22085858 TI - Molecular biology. Nature of the genetic code finally revealed! PMID- 22085859 TI - Animals learn new tricks from microorganisms. PMID- 22085860 TI - Phosphonium-based ionic liquids as modifiers for biomedical grade poly(vinyl chloride). AB - This work reports and discusses the influence of four phosphonium-based ionic liquids (PhILs), namely trihexyl(tetradecyl) phosphonium dicyanamide, [P(6,6,6,14)][dca]; trihexyl(tetradecyl) phosphonium bis(trifluoromethylsulfonyl)imide, [P(6,6,6,14)][Tf(2)N]; tetrabutyl phosphonium bromide, [P(4,4,4,4)][Br]; and tetrabutyl phosphonium chloride, [P(4,4,4,4)][Cl], on some of the chemical, physical and biological properties of a biomedical-grade suspension of poly(vinyl chloride) (PVC). The main goal of this work was to evaluate the capacity of these PhILs to modify some of the properties of neat PVC, in particular those that may allow their use as potential alternatives to traditional phthalate-based plasticizers in PVC biomedical applications. PVC films having different PhIL compositions (0, 5, 10 and 20 wt.%) were prepared (by solvent film casting) and characterised by Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, dynamical mechanical thermal analysis, scanning electron microscopy/energy-dispersive X ray/electron probe microanalysis, X-ray diffraction, transmittance, permeability towards oxygen and carbon dioxide, thermal degradation, contact angle measurement, water and vapour uptake, leachability and biocompatibility (haemolytic potential, thrombogenicity and cytotoxicity). A conventional organic plasticizer (di-isononyl phthalate) was used for comparison purposes. The results obtained showed that it was possible to change the neat PVC hydrophobicity, and consequently its water uptake capacity and plasticizer leachability, just by changing the PhIL employed and its composition. It was also possible to significantly change the thermal and mechanical properties of PVC films by choosing appropriate PhIL cation/anion combinations. However, a specific PhIL may not always be capable of simultaneously keeping and/or improving both physical properties. In addition, ionic halide salts were found to promote PVC dehydrochlorination. Finally, none of the prepared materials presented toxicity against Caco-2 cells, though pure [P(6,6,6,14)][dca] decreased HepG2 cells viability. Moreover, PVC films with [P(6,6,6,14)][dca] and [P(4,4,4,4)][Cl] were found to be haemolytic and thus these PhILs must be avoided as PVC modifiers if biomedical applications are envisaged. In conclusion, from all the PhILs tested, [P(6,6,6,14)][Tf(2)N] showed the most promising results regarding blood compatibility, leaching and permeability to gases of PVC films. The results presented are a strong indicator that adequate PhILs may be successfully employed as PVC multi-functional plasticizers for a wide range of potential applications, including those in the biomedical field. PMID- 22085861 TI - Rigorous and thorough bioinformatic analyses of olfactory receptor promoters confirm enrichment of O/E and homeodomain binding sites but reveal no new common motifs. AB - BACKGROUND: Mammalian olfactory receptors (ORs) are subject to a remarkable but poorly understood regime of transcriptional regulation, whereby individual olfactory neurons each express only one allele of a single member of the large OR gene family. RESULTS: We performed a rigorous search for enriched sequence motifs in the largest dataset of OR promoter regions analyzed to date. We combined measures of cross-species conservation with databases of known transcription factor binding sites and ab initio motif-finding algorithms. We found strong enrichment of binding sites for the O/E family of transcription factors and for homeodomain factors, both already known to be involved in the transcriptional control of ORs, but did not identify any novel enriched sequences. We also found that TATA-boxes are present in at least a subset of OR promoters. CONCLUSIONS: Our rigorous approach provides a template for the analysis of the regulation of large gene families and demonstrates some of the difficulties and pitfalls of such analyses. Although currently available bioinformatics methods cannot detect all transcriptional regulatory elements, our thorough analysis of OR promoters shows that in the case of this gene family, experimental approaches have probably already identified all the binding factors common to large fractions of OR promoters. PMID- 22085862 TI - Formononetin protects neurons against hypoxia-induced cytotoxicity through upregulation of ADAM10 and sAbetaPPalpha. AB - Formononetin, an active constituent of the Chinese herb Astragali Radix, has been reported to have beneficial effects for Alzheimer's disease (AD). Yet the mechanism of this effect remains to be elucidated. The present study shows that formononetin increases soluble-AbetaPPalpha (sAbetaPPalpha) secretion and thus protects human-AbetaPP Swedish mutation cell (N2a-AbetaPP cell) from hypoxia induced apoptosis. Using hypoxic N2a-AbetaPP cell as an in vitro model of AD-like pathology, we confirmed that regular treatment with formononetin could have neuroprotective effects, followed respectively by reduced caspase 3 activity and increased cell viability. Strikingly, our data revealed that the caspase 3 blocking effect of formononetin was largely mediated by stimulation of alpha secretase cleavage of AbetaPP, and increasing the secretion of its soluble form, sAbetaPPalpha. Moreover, the protective effect of formononetin was totally inhibited by TAPI-2, an alpha-secretase complex inhibitor, suggesting the role of the sAbetaPPalpha pathway in the neuroprotective response to formononetin. We also found that the stimulative effect of formononetin on alpha-secretase activity was mainly conducted by upregulating ADAM10 expression at the transcriptional level. Altogether, our study provides novel insights into how formononetin mediates stimulation of the ADAM10-sAbetaPPalpha pathway and exerts a neuronal protective effect. PMID- 22085863 TI - Neural dissociation in processing noise and accent in spoken language comprehension. AB - We investigated how two distortions of the speech signal - added background noise and speech in an unfamiliar accent - affect comprehension of speech using functional Magnetic Resonance Imaging (fMRI). Listeners performed a speeded sentence verification task for speech in quiet in Standard Dutch, in Standard Dutch with added background noise and for speech in an unfamiliar accent of Dutch. The behavioural results showed slower responses for both types of distortion compared to clear speech, and no difference between the two distortions. The neuroimaging results showed that, compared to clear speech, processing noise resulted in more activity bilaterally in Inferior Frontal Gyrus, Frontal Operculum, while processing accented speech recruited an area in left Superior Temporal Gyrus/Sulcus. It is concluded that the neural bases for processing different distortions of the speech signal dissociate. It is suggested that current models of the cortical organisation of speech are updated to specifically associate bilateral inferior frontal areas with processing external distortions (e.g., background noise) and left temporal areas with speaker-related distortions (e.g., accents). PMID- 22085864 TI - Visuomotor performance based on peripheral vision is impaired in the visual form agnostic patient DF. AB - The perception-action model states that visual information is processed in different cortical areas depending on the purpose for which the information is acquired. Specifically, it was suggested that the ventral stream mediates visual perception, whereas the dorsal stream primarily processes visual information for the guidance of actions (Goodale & Milner, 1992). Evidence for the model comes from patient studies showing that patients with ventral stream damage (visual form agnosia) and patients with dorsal stream damage (optic ataxia) show divergent performance in action and perception tasks. Whereas DF, a patient suffering from visual form agnosia, was found to perform well in visuomotor tasks despite her inability to use vision for perceptual tasks, patients with optic ataxia show usually the opposite pattern, i.e. good perception but impaired visuomotor control. The finding that both disorders seem to provoke a mirror reversed pattern of spared and impaired visual functions, led to the belief that optic ataxia and visual form agnosia can be considered as complementary disorders. However, the visuomotor performance of patients with optic ataxia is typically only impaired when they are tested in visual periphery while being often preserved when tested in central vision. Here, we show that DF's visuomotor performance is also only preserved when the target is presented centrally. Her reaching and grasping movements to targets in peripheral vision are abnormal. Our findings indicate that DF's visuomotor performance is quite similar to the visuomotor performance of patients with optic ataxia which undermines previous suggestions that the two disorders form a double-dissociation. PMID- 22085865 TI - The effects of railroad ballast surface and slope on rearfoot motion in walking. AB - The purpose of this study was to investigate the effects of transversely sloped ballasted walking surface on gait and rearfoot motion (RFM) parameters. Motion analysis was performed with 20 healthy participants (15 male and 5 female) walking in six surface-slope conditions: two surfaces (solid and ballasted) by three slopes (0, 5, and 10 degrees). The gait parameters (walking velocity, step length, step rate, step width, stance time, and toe-out angle) showed significant surface effect (p = .004) and surface-slope interaction (p = .017). The RFM motion parameters (peak everted/inverted position, eversion/inversion velocity, and acceleration) revealed significant surface (p = .004) and slope (p = .024) effects. The ballasted conditions showed more cautious gait patterns with lower walk velocity, step length, and step rate and longer stance time. In the RFM parameters, the slope effect was more notable in the solid conditions due to the gait adaptations in the ballasted conditions. Ballast conditions showed reduced inversion and increased eversion and RFM range. The RFM data were comparable to other typical walking conditions but smaller than those from running. PMID- 22085866 TI - Improvement in cardiac function following transplantation of human umbilical cord matrix-derived mesenchymal cells. AB - OBJECTIVES: Human umbilical cord mesenchymal cells (hUCM) can be easily obtained and processed in a laboratory. These cells may be considered as a suitable source in the repair of heart failure diseases. We, therefore, examined whether these cells may contribute to heart regeneration following an acute experimental myocardial infarction (MI). METHODS: MI-induced animals received 5 * 10(6) hUCM cells, 5 * 10(6) 5-azacytidine-treated cells (dhUCM), or PBS alone, subepicardially. A group of animals with MI and no other former intervention served as controls. dhUCM cells were assessed for F-actin, myogenin and troponin I expression. RESULTS: dhUCM cells appeared as binucleated cells with extensive cytoplasmic processes. These differentiated cells were F-actin and myogenin positive. Thirty days after LAD ligation, left ventricular ejection fraction and the percentage of fractional shortening improved significantly in cell-receiving animals. In addition, the amount of scar tissue was significantly reduced in hUCM and dhUCM groups compared to MI group (p < 0.05). These parameters were comparable between hUCM and dhUCM groups. Histopathological evaluations revealed that some engrafted cells adjacent to and remote from the MI area expressed troponin-I, F-actin and connexin43. CONCLUSION: These findings demonstrated the potential therapeutic use of either differentiated or undifferentiated hUCM cells in treatment of heart failure conditions. PMID- 22085867 TI - A longitudinal evaluation of growth outcomes at hospital discharge of very-low birth-weight preterm infants. AB - BACKGROUND/OBJECTIVES: To quantify the rate of progressive failure of very-low birth-weight (VLBW) infants over time in the neonatal intensive care unit to meet growth milestones. SUBJECTS/METHODS: In a prospective longitudinal study, 114 VLBW preterm infants (?1500 g) of both sexes, with normal and/or low weight for gestational age were included. At the start, weight, length, mid-upper arm (MUAC), thigh and cephalic circumferences were measured. Weight/age (W/A), length/age and weight/length (+/-2 z-score) indices were calculated. All measurements were taken at inclusion, at 7, 15 and 30 days of hospitalization. Chi-square test, analysis of variance and repeated-measures tests were estimated. RESULTS: Thirteen cases (14%) died and were excluded soon after the first determinations. In all, 9 (8.9%) died during the study, 12 (11.9%) were discharged before 30 days of life and 80 (79.2%) completed the study. At 7 days, the percentage of preterm infants with an index of W/A <-2 z-scores increased from 44 to 67% (44-68 subjects; P<0.01), with no changes afterwards; the indicator MUAC <-2 z-scores increased at 7 days from 23 to 49% (23-49 subjects); at 15 from 23 to 65% (23-61 subjects) and at 30 days from 23 to 79% (23-63 subjects; P<0.001). CONCLUSIONS: Clinicians could use these indicators for earlier detection of growth failure in VLBW infants in order to target more aggressive nutrition early. PMID- 22085868 TI - Alcohol and macronutrient intake patterns are related to general and central adiposity. AB - BACKGROUND/OBJECTIVES: Alcohol and dietary fat have high energy densities and may therefore be related to body weight and fat deposition. We studied associations between alcohol and macronutrient intake patterns and general and central adiposity. SUBJECTS/METHODS: A population-based cross-sectional study of 524 men and 611 women. The participants answered a dietary questionnaire describing habitual food consumption including intake of alcoholic beverages. Macronutrient intake was analysed in relation to anthropometric measures and dual energy X-ray absorptiometry determined body fat. RESULTS: In women, total alcohol intake was negatively associated with body fat percentage (beta:-0.67, P<0.01). In men, total alcohol intake was positively associated with sagittal abdominal diameter (SAD) (beta: 0.28, P=0.01). In addition, positive associations were found between intake of alcohol from spirits and body fat percentage (beta: 1.17, P<0.05), SAD (beta: 0.52, P<0.05) and waist circumference (beta: 2.29, P=0.01). In men, protein intake was positively associated with body mass index (BMI) (beta: 0.03, P=0.001), body fat percentage (beta: 0.04, P<0.05), SAD (beta: 0.02, P=0.01) and waist circumference (beta: 0.09, P<0.01). Also in men only, negative associations between fat intake and BMI (beta: -0.03, P<0.01), SAD (beta: -0.02, P<0.05) and waist circumference (beta: -0.05, P<0.05) were found. CONCLUSIONS: Alcohol intake was inversely associated to relative body fat in women whereas spirits consumption was positively related to central and general obesity in men. Macronutrient intakes, particularly protein and fat, were differently associated with obesity indicators in men versus women. This may reflect a differential effect by gender, or differential obesity related reporting errors in men and women. PMID- 22085869 TI - No effect of maternal micronutrient supplementation on early childhood growth in rural western China: 30 month follow-up evaluation of a double blind, cluster randomized controlled trial. AB - BACKGROUND/OBJECTIVES: Little is known about the long-term effects of maternal multi-micronutrient supplementation on the growth of children during early childhood. In this follow-up study, the effects of maternal supplementation with multi-micronutrients in pregnancy on postnatal child growth are examined. SUBJECTS/METHODS: A longitudinal follow-up of a subset of newborns (n=1388) whose mothers were randomly assigned to receive the supplements of folic acid, iron folic acid or multi-micronutrients daily during pregnancy in the original trial was conducted. Children's weight and length were measured and assessed during monthly home visits from birth to 30 months of age. RESULTS: The pooled prevalence rate of stunting over different time points during the first 30 months was 13.5, 14.9 and 12.1% for the folic acid group, iron-folic acid group and multi-micronutrient group, respectively. However, there were no significant differences in the pooled odds of stunting in children between the multi micronutrient group and the folic acid (odds ratio (OR) 0.97, 95% confidence interval (CI): 0.74-1.26), and between the multi-micronutrient group and the iron folic acid group (OR 0.82, 95% CI: 0.63-1.07). Similar results for the three groups were found for the occurrences of underweight and wasting in children. Furthermore, no significant differences were observed in length, weight, length for-age, weight-for-age and weight-for-length Z-scores among the three treatment groups. CONCLUSIONS: Currently, available evidence is insufficient to support a greater advantage of the effect of maternal multi-micronutrient supplementation on child growth over iron-folic acid or folic acid only supplementation during the first 30 months. PMID- 22085870 TI - Effect of nutrition education on exclusive breastfeeding for nutritional outcome of low birth weight babies. AB - BACKGROUND/OBJECTIVES: Low birth weight (LBW), defined as the body weight at birth of less than 2500 g, is a major public health problem in Bangladesh, where 37% of the babies are born with LBW. The objective of this study is to see the impact of nutrition education on growth of LBW babies with early initiation and exclusive breastfeeding compared to control group. SUBJECTS/METHODS: A total of 184 LBW babies and their mothers who attended the Maternal Care and Health Training Institute and Dhaka Medical College Hospital were randomly allocated to either intervention or control group. Enrollment of the study population started in May 2008 and was completed in October 2008. Nutrition education was given to mothers twice weekly for 2 months, on initiation of breastfeeding within 1 h, exclusive breastfeeding and increasing their dietary intake. Nutritional status of LBW babies was assessed for length and weight every 2 weeks. Data were analyzed using SPSS/Window's version 12. Comparison of mean of data was done using standard Student's t-test. RESULTS: Mean initial body weight and length of LBW babies were similar in both groups (2261+/-198 g vs 2241+/-244 g, P=0.535 and 43.0+/-1.3 cm vs 43.0+/-1.7 cm, P=0.77). Body weight and length of the LBW babies after 2 months increased significantly (3620+/-229 g vs 3315+/-301 g, P<0.001 and 50.2+/-1.3 cm vs 48.7+/-1.6 cm, P<0.001). It was found that the intervention group suffered less from respiratory illness compared with the control group (39% vs 66%, P<0.001). The rate of early initiation of breastfeeding was also significantly higher with nutrition intervention (59.8% vs 37.2%, P<0.001). Exclusive breastfeeding rate was significantly higher in intervention group (59.8% vs 37%, P=0.003). CONCLUSIONS: The present study showed that weight and length gain of LBW babies significantly increased by breastfeeding and nutrition education. Therefore, nutrition education on breastfeeding proves to be a strong tool to reduce the high risk of malnutrition and mortality of the LBW babies. PMID- 22085871 TI - Consuming a diet complying with front-of-pack label criteria may reduce cholesterol levels: a modeling study. AB - BACKGROUND/OBJECTIVES: Front-of-pack nutrition labels can help consumers to make healthier choices and stimulate healthier product development. This is the first modeling study to investigate the potential impact on cholesterol levels of consuming a diet consisting of products that comply with the criteria for a 'healthier choice logo'. SUBJECTS/METHODS: National food consumption and food composition data were used to estimate the nutrient intake of the Dutch adult population (18-70 years) before and after replacing foods that did not comply with the choices front-of-pack label criteria. Different scenarios were established. The difference in cholesterol levels in the Dutch population was assessed before and after replacement by means of equations from meta-analyses that calculate how blood lipids change when diet composition changes. RESULTS: After replacing non-complying products with products, which comply with the label's criteria (maximum scenario), saturated fatty acids median intake reduced from 14.5 to 9.8 en%. Trans-fatty acids reduced from 0.95 to 0.57 en%. The average predicted changes in low-density lipoprotein and total cholesterol levels were -0.25 and -0.31 mmol/l, respectively. Because high-density lipoprotein (HDL) cholesterol levels reduced as well (-0.05 mmol/l), overall, the result was a slightly positive change in the total cholesterol/HDL ratio (-0.03). CONCLUSIONS: Our findings suggest that the consumption of foods complying with the criteria for a front-of-pack label could contribute moderately to cardiovascular risk reduction via influencing blood lipids. These findings were independent of other potential effects on related health outcomes. PMID- 22085872 TI - Effect of folic acid intervention on ALT concentration in hypertensives without known hepatic disease: a randomized, double-blind, controlled trial. AB - BACKGROUND/OBJECTIVES: Increasing evidence suggests that altered methionine/folate metabolism may contribute to the development of hepatic injury. We addressed the question of whether folic acid (FA) supplementation can affect serum alanine aminotransferase (ALT) level in hypertensive Chinese adults. SUBJECTS/METHODS: A total of 480 participants with mild or moderate essential hypertension and without known hepatic disease were randomly assigned to three treatment groups: (1) enalapril only (10 mg, control group); (2) enalapril-FA tablet (10 mg enalapril combined with 0.4 mg of FA, low FA group); and (3) enalapril-FA tablet (10 mg enalapril combined with 0.8 mg of FA, high FA group), once daily for 8 weeks. RESULTS: This report included 455 participants in the final analysis according to the principle of intention to treat. We found a significant reduction in ALT level in the high FA group (median (25th percentile, 75th percentile), -0.6 (-6.9, 2.0)IU/l, P=0.0008). Compared with the control group, the high FA group showed a significantly greater ALT-lowering response in men (median ALT ratio (ALT at week 8 to ALT at baseline; 25th percentile, 75th percentile): 0.93 (0.67, 1.06) vs 1.00 (0.91, 1.21), P=0.032), and in participants with elevated ALT (ALT>40 IU/l) at baseline. There was no difference in ALT lowering between the control and the low FA group. CONCLUSIONS: Compared with treatment using 10 mg of enalapril alone, a daily dose of 10 mg enalapril combined with 0.8 mg of FA showed a beneficial effect on serum ALT level, particularly in men and in participants with elevated (>40 IU/l) ALT. PMID- 22085873 TI - Paraneoplastic syndrome mimicking adult-onset Still's disease caused by advanced lung cancer: a case report. AB - BACKGROUND: Paraneoplastic syndromes (PNSs) are common complications of lung cancer and often develop preceding the diagnosis of primary malignancy. Rheumatologic PNSs mimicking Adult-Onset Still' s Disease (AOSD) is a rare condition with only a limited number of cases reported in the literature, none of which was associated with lung cancer. It is often difficult to differentiate AOSD-like paraneoplasia from coincidental AOSD based on the clinical manifestations. CASE PRESENTATION: Here we present a 56-year-old man with advanced lung adenocarcinoma who developed a remittent fever together with pharyngodynia and joint pain after first cycle of chemotherapy with paclitaxel plus carboplatin. Although a leukocytosis was detected, no evidence of infection was acquired and empirical antibiotic treatment was ineffective. A temple skin rash, abnormal hepatic function and a remarkable elevated level of serum ferritin occurred later in this patient, which highly supported a potential diagnosis of AOSD. The patient was finally diagnosed as AOSD-like PNS considering the good and prompt response to a short-term administration of non-steroidal anti-inflammatory drug and subsequent cycles of effective chemotherapy with pemetrexed plus cisplatin. DISCUSSION AND CONCLUSIONS: Though rare, AOSD-like PNS can be one of the potential diagnoses in lung cancer patients with fever of undetermined origin, especially those having no response to antibiotic treatment. Management consists of control of the underlying malignancy and symptomatic treatment of the syndromes with non-steroidal anti-inflammatory drugs or corticosteroids. PMID- 22085874 TI - Selective formation of angular tricyclic compounds by ruthenium-mediated ring rearrangement metathesis. AB - Unsaturated spirocyclic substrates bearing two alkenyl chains underwent ruthenium mediated ring-rearrangement metathesis through relaying cyclohexene and cycloheptene moieties to give angularly fused tricyclics. In some instances where two products were expected, high degrees of selectivity were observed. In one instance the structural parameter leading to selectivity was very subtle; in others the transformation favoured the formation of products with a cis-fused cyclohexene moiety. An unusual transformation involving ring-opening, double-bond migration, and then ring-closing was observed. PMID- 22085875 TI - Temporal and frontal lobe initiation and regulation of the top-down escalation of anger and aggression. AB - The widespread, across-species strategy of stagewise escalation of aggression in agonistic encounters can be understood in terms of resource capture and control with least risk and cost. Human anger likely follows similar principles. As an adaptive phenomenon, escalation may involve particular neural circuitry. To advance beyond a standard view that the frontal lobe tonically inhibits subcortical circuits of aggression, a model is proposed which starts with the general rostrally directed flow of information in the brain. Earlier stage processing of visual and auditory input is transmitted from posterior and middle temporal cortices to anterior temporal lobe where rudimentary appraisals of threat and provocation are developed. These directly but diffusely activate cortical/subcortical anger/aggression response systems. At the same time, the anterior temporal loci transmit the modality-specific perceptual information to orbito-frontal cortex where it is integrated with information about, e.g., the opponent's relative dominance/social status and evaluated for likelihood of potential rewards and punishments associated with different modes of responding and so forth. These frontal areas then impose an inhibitory gating or modulation and focusing of activity initiated by the anterior temporal loci through their projections to GABAergic interneurons in the same cortical/subcortical circuits. Escalation occurs as the inhibition imposed by the frontal areas is progressively lifted. Exploration of the implications, applications and hypotheses flowing from this model will improve our understanding of the biologically important and socially significant phenomena of escalation. PMID- 22085877 TI - Systemic treatment with the enteric bacterial fermentation product, propionic acid, produces both conditioned taste avoidance and conditioned place avoidance in rats. AB - Propionic acid, an enteric bacterial fermentation product, has received recent attention in regards to satiety and obesity in humans. The possibility that propionic acid might produce internal aversive cues was investigated in two experiments using conditioned taste avoidance and place avoidance procedures to index the potential aversive nature of systemic treatment with propionic acid in male rats. Experiment 1 examined the effect of systemic treatment with propionic acid (500 mg/kg), LiCl (95 mg/kg) or vehicle (all corrected to pH 7.5) on the formation of conditioned taste avoidance using a lickometer procedure. On 3 acquisition days three groups of rats were injected with propionic acid, LiCl or vehicle, following 30 min access to 0.3M sucrose solution. Both the Propionic acid group and the LiCl group evidenced a conditioned taste avoidance by the end of the acquisition period. During a drug free extinction phase the Propionic acid group showed extinction of the taste avoidance whereas the LiCl group did not. Experiment 2 involved place preference conditioning with propionic acid treatment associated with one novel context and vehicle with a different novel context on 6 conditioning trials for each type of injection. Place avoidance was assessed on two drug free extinction trials. Multi-variable assessment of the unconditioned (Acquisition Trials) and conditioned effects (Extinction Trials) of propionic acid on locomotor activity was quantified as was chamber choice time on the extinction trials. Propionic acid induced a significant place avoidance and significantly reduced locomotor activity on some acquisition trials. During the extinction trials rats exhibited enhanced locomotor activity levels in the propionic acid associated chamber, likely due to the conditioned aversive nature of this chamber. PMID- 22085876 TI - Muscarinic receptor/G-protein coupling is reduced in the dorsomedial striatum of cognitively impaired aged rats. AB - Behavioral flexibility, the ability to modify responses due to changing task demands, is detrimentally affected by aging with a shift towards increased cognitive rigidity. The neurobiological basis of this cognitive deficit is not clear although striatal cholinergic neurotransmission has been implicated. To investigate the possible association between striatal acetylcholine signaling with age-related changes in behavioral flexibility, young, middle-aged, and aged F344 X Brown Norway F1 rats were assessed using an attentional set-shifting task that includes two tests of behavioral flexibility: reversal learning and an extra dimensional shift. Rats were also assessed in the Morris water maze to compare potential fronto-striatal-dependent deficits with hippocampal-dependent deficits. Behaviorally characterized rats were then assessed for acetylcholine muscarinic signaling within the striatum using oxotremorine-M-stimulated [(35)S]GTPgammaS binding and [(3)H]AFDX-384 receptor binding autoradiography. The results showed that by old age, cognitive deficits were pronounced across cognitive domains, suggesting deterioration of both hippocampal and fronto-striatal regions. A significant decline in oxotremorine-M-stimulated [(35)S]GTPgammaS binding was limited to the dorsomedial striatum of aged rats when compared to young and middle-aged rats. There was no effect of age on striatal [(3)H]AFDX-384 receptor binding. These results suggest that a decrease in M2/M4 muscarinic receptor coupling is involved in the age-associated decline in behavioral flexibility. PMID- 22085878 TI - Consequences of early life MK-801 administration: long-term behavioural effects and relevance to schizophrenia research. AB - Animal models contribute significantly to advancing the understanding of schizophrenia neurobiology, in addition to being an important tool for the screening of antipsychotic potential of new compounds. However, the entire spectrum or all the symptoms manifested in schizophrenia cannot be straightforwardly reproduced in animals due to the complexity of the disorder, difference in mental capacities and behaviours, and the ability to quantify or measure the changes. Blockade of the NMDA receptor by the use of MK-801, a non competitive NMDA receptor antagonist, during the early postnatal period has been proposed to be an experimental model which induces behavioural changes that mimic several aspects of the disorder. The long term behavioural profile arising from this early life manipulation is reviewed herein, with a specific focus on behaviours relevant to a schizophrenia-like condition. Some of the reported neurochemical changes are also compiled. Although this method may be suitable to model some aspects of schizophrenia in rodents, there are unmet areas which need to be addressed, notably the characterisation of its predictive value. PMID- 22085879 TI - Neuropeptide Trefoil factor 3 improves learning and retention of novel object recognition memory in mice. AB - Accumulating evidence has implicated neuropeptides in modulating recognition, learning and memory. However, to date, no study has investigated the effects of neuropeptide Trefoil factor 3 (TFF3) on the process of learning and memory. In the present study, we evaluated the acute effects of TFF3 administration (0.1 and 0.5mg/kg, i.p.) on the acquisition and retention of object recognition memory in mice. We found that TFF3 administration significantly enhanced both short-term and long-term memory during the retention test, conducted 90 min and 24h after training respectively. Remarkably, acute TFF3 administration transformed a learning event that would not normally result in long-term memory into an event retained for a long-term period and produced no effect on locomotor activity in mice. In conclusion, the present results provide an important role of TFF3 in improving object recognition memory and reserving it for a longer time, which suggests a potential therapeutic application for diseases with recognition and memory impairment. PMID- 22085880 TI - Synaptic transmission changes in fear memory circuits underlie key features of an animal model of schizophrenia. AB - Non-competitive antagonists of the N-methyl-d-aspartate receptor (NMDA) such as phencyclidine (PCP) elicit schizophrenia-like symptoms in healthy individuals. Similarly, PCP dosing in rats produces typical behavioral phenotypes that mimic human schizophrenia symptoms. Although schizophrenic behavioral phenotypes of the PCP model have been extensively studied, the underlying alterations of intrinsic neuronal properties and synaptic transmission in relevant limbic brain microcircuits remain elusive. Acute brain slice electrophysiology and immunostaining of inhibitory neurons were used to identify neuronal circuit alterations of the amygdala and hippocampus associated with changes in extinction of fear learning in rats following PCP treatment. Subchronic PCP application led to impaired long-term potentiation (LTP) and marked increases in the ratio of NMDA to 2-amino-3(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor mediated currents at lateral amygdala (LA) principal neurons without alterations in parvalbumin (PV) as well as non-PV, glutamic acid decarboxylase 67 (GAD 67) immunopositive neurons. In addition, LTP was impaired at the Schaffer collateral to CA1 hippocampal pathway coincident with a reduction in colocalized PV and GAD67 immunopositive neurons in the CA3 hippocampal area. These effects occurred without changes in spontaneous events or intrinsic membrane properties of principal cells in the LA. The impairment of LTP at both amygdalar and hippocampal microcircuits, which play a key role in processing relevant survival information such as fear and extinction memory concurred with a disruption of extinction learning of fear conditioned responses. Our results show that subchronic PCP administration in rats impairs synaptic functioning in the amygdala and hippocampus as well as processing of fear-related memories. PMID- 22085881 TI - Impaired egocentric memory and reduced somatosensory cortex size in temporal lobe epilepsy with hippocampal sclerosis. AB - Recent research indicates that longstanding temporal lobe epilepsy (TLE) is associated with extratemporal, i.e. parietal cortex damage. We investigated egocentric and allocentric memory by use of first-person large-scale virtual reality environments in patients with TLE. We expected that TLE patients with parietal cortex damage were impaired in the egocentric memory task. Twenty-two TLE patients with hippocampal sclerosis (HS) and 22 TLE patients without HS were compared with 42 healthy matched controls on two virtual reality tasks affording to learn a virtual park (allocentric memory) and a virtual maze (egocentric memory). Participants further received a neuropsychological investigation and MRI volumetry at the time of the assessment. When compared with controls, TLE patients with HS had significantly reduced size of the ipsilateral and contralateral somatosensory cortex (postcentral gyrus). When compared with controls or TLE patients without HS, TLE patients with HS were severely impaired learning the virtual maze. Considering all participants, smaller volumes of the left-sided postcentral gyrus were related to worse performance on the virtual maze. It is concluded that the paradigm of egocentric navigation and learning in first-person large-scale virtual environments may be a suitable tool to indicate significant extratemporal damage in individuals with TLE. PMID- 22085882 TI - 17beta-estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas. AB - Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17beta-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF. 17beta-Estradiol treatment did not influence animals' locomotor activity and exploratory behavior, but it was able to improve the performance of adult and middle-aged rats in the Morris water maze, the latter being more responsive to the treatment. Young and adult rats displayed decreased immobility time in the forced swimming test, suggesting an effect of 17beta-estradiol also over such depressive-like behavior. This same test revealed increased swimming behavior, triggered by serotonergic pathway, in adult rats. Neurochemical evaluations indicated that 17beta-estradiol treatment was able to increase serotonin turnover rate in the hippocampus of adult rats. Interestingly, estrogen treatment increased BDNF levels from animals of all ages. These findings support the notion that the beneficial effects of 17beta-estradiol over spatial reference memory and depressive-like behavior are evident only when hormone therapy occurs at early ages and early stages of hormonal decline. PMID- 22085883 TI - Coping in an intermittent swim stress paradigm compromises natural killer cell activity in rats. AB - The effects of intermittent swim stress and stressor controllability on natural killer cell activity (NKCA) was examined. Significant decreases in splenic NKCA were observed immediately post-stress, but only when the stress was controllable. Although decreased NKCA was also observed in yoked rats subjected to the same stressor, it failed to attain statistical significance. Previous results suggest these effects are not due to corticosterone. The results suggest a cost of coping on the acute, in vitro immune measure of NKCA. PMID- 22085884 TI - What do we know about aging and spatial cognition? Reviews and perspectives. AB - In order to cope with normal cognitive aging we must understand the patterns and neurofunctional underpinnings of cognitive and behavioral changes throughout adulthood. In this review, we summarize recent advances in our understanding of age-related behavioral differences and changes in brain structure throughout the spatial domain. Although spatial cognition is critically important to everyday life, few studies have examined the relationship between this cognitive function and neural changes in the aged brain. Thus, spatial cognition is considered a key area in which the cognitive neuroscience of aging may expand in the near future. The first section of this review examines the methodologies and studies used to assess differences in spatial cognition during normal cognitive aging in animals and humans. We then relate how each domain of spatial cognition (e.g., visuospatial perception, mental imagery, memory and navigation) is affected by the aging process, and discuss possible links with changes in neural mechanisms. Lastly, we address putative links among the age-related deterioration patterns of the various spatial domains and make suggestions for future research. PMID- 22085886 TI - Effects of the commensurability and disorder on friction for the system Xe/Cu. AB - We present molecular dynamics simulations of static friction for a monolayer of Xe deposited on a thick slab of Cu for two different geometries. The interaction potential between Xe and Cu has been derived from DFT calculations. The first geometry is the commensurate adsorption geometry (?3 * ?3 suggested by LEED, corresponding to a coverage 1/3, where all Xe atoms are on top positions. The second one corresponds to a coverage 0.36 and is characterized by a large surface unit cell, containing 9 Xe atoms in different disordered positions. This large unit cell mimics an incommensurate case. Our analysis points out the effect of the order/disorder in tribological properties of a realistic three-dimensional system. PMID- 22085885 TI - Age effect on myocellular remodeling: response to exercise and nutrition in humans. AB - Aging is associated with decline in muscle mass and muscle functions. Muscle strength declines disproportionate to the decline in muscle mass indicating that muscle quality or protein quality also declines with age. Human studies have shown a progressive decline in muscle protein synthesis including proteins in the contractile apparatus and mitochondria with age. However, the decline in muscle protein synthesis is disproportionate to the decline in muscle mass that occurs with age prompting to hypothesize that muscle protein degradation also declines with age. A decline in mitochondrial capacity to synthesize ATP is likely a limiting factor of both synthesis and degradation, which are ATP dependent processes. In support of the above hypothesis, several studies have shown a decline in whole body protein turnover (synthesis and degradation). The timely and efficient degradation of irreversibly damaged or modified proteins is critical to maintain the quality of protein. It is proposed that a failure to degrade the damaged proteins and replacing them with newly synthesized proteins contribute to age related decline in muscle mass and quality of muscle proteins. The underlying molecular mechanism of these age related changes in human muscle needs further investigation. PMID- 22085887 TI - Effects of genome-wide copy number variation on expression in mammalian cells. AB - BACKGROUND: There is only a limited understanding of the relation between copy number and expression for mammalian genes. We fine mapped cis and trans regulatory loci due to copy number change for essentially all genes using a human hamster radiation hybrid (RH) panel. These loci are called copy number expression quantitative trait loci (ceQTLs). RESULTS: Unexpected findings from a previous study of a mouse-hamster RH panel were replicated. These findings included decreased expression as a result of increased copy number for 30% of genes and an attenuated relationship between expression and copy number on the X chromosome suggesting an Xist independent form of dosage compensation. In a separate glioblastoma dataset, we found conservation of genes in which dosage was negatively correlated with gene expression. These genes were enriched in signaling and receptor activities. The observation of attenuated X-linked gene expression in response to increased gene number was also replicated in the glioblastoma dataset. Of 523 gene deserts of size > 600 kb in the human RH panel, 325 contained trans ceQTLs with -log10 P > 4.1. Recently discovered genes, ultra conserved regions, noncoding RNAs and microRNAs explained only a small fraction of the results, suggesting a substantial portion of gene deserts harbor as yet unidentified functional elements. CONCLUSION: Radiation hybrids are a useful tool for high resolution mapping of cis and trans loci capable of affecting gene expression due to copy number change. Analysis of two independent radiation hybrid panels show agreement in their findings and may serve as a discovery source for novel regulatory loci in noncoding regions of the genome. PMID- 22085888 TI - EVP-6124, a novel and selective alpha7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of alpha7 nicotinic acetylcholine receptors. AB - EVP-6124, (R)-7-chloro-N-quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide, is a novel partial agonist of alpha7 neuronal nicotinic acetylcholine receptors (nAChRs) that was evaluated here in vitro and in vivo. In binding and functional experiments, EVP-6124 showed selectivity for alpha7 nAChRs and did not activate or inhibit heteromeric alpha4beta2 nAChRs. EVP-6124 had good brain penetration and an adequate exposure time. EVP-6124 (0.3 mg/kg, p.o.) significantly restored memory function in scopolamine-treated rats (0.1 mg/kg, i.p.) in an object recognition task (ORT). Although donepezil at 0.1 mg/kg, p.o. or EVP-6124 at 0.03 mg/kg, p.o. did not improve memory in this task, co-administration of these sub efficacious doses fully restored memory. In a natural forgetting test, an ORT with a 24 h retention time, EVP-6124 improved memory at 0.3 mg/kg, p.o. This improvement was blocked by the selective alpha7 nAChR antagonist methyllycaconitine (0.3 mg/kg, i.p. or 10 MUg, i.c.v.). In co-application experiments of EVP-6124 with acetylcholine, sustained exposure to EVP-6124 in functional investigations in oocytes caused desensitization at concentrations greater than 3 nM, while lower concentrations (0.3-1 nM) caused an increase in the acetylcholine-evoked response. These actions were interpreted as representing a co-agonist activity of EVP-6124 with acetylcholine on alpha7 nAChRs. The concentrations of EVP-6124 that resulted in physiological potentiation were consistent with the free drug concentrations in brain that improved memory performance in the ORT. These data suggest that the selective partial agonist EVP 6124 improves memory performance by potentiating the acetylcholine response of alpha7 nAChRs and support new therapeutic strategies for the treatment of cognitive impairment. This article is part of a Special Issue entitled 'Post Traumatic Stress Disorder'. PMID- 22085889 TI - Efficacy and safety of a tight glucose control protocol in critically ill term neonates. AB - BACKGROUND: A large single-center randomized trial showed that treating hyperglycemia in critically ill children improved outcome, despite an increased incidence of hypoglycemia, especially in infants. OBJECTIVES: We evaluated the efficacy and incidence of hypoglycemia using a tight glucose protocol in critically ill term neonates. METHODS: Term hyperglycemic (>8 mmol.l(-1); >144 mg.dl(-1)) neonates treated with a tight glucose protocol during a 3.5-year period in a tertiary pediatric intensive care unit were retrospectively analyzed. RESULTS: Seventy-three term hyperglycemic neonates [age 0 days (0-6), weight 3.2 +/- 0.8 kg, PRISM 16 (11-20)] were included for analysis. Eighteen neonates died (25%). The initial mean (range) glucose level was 11.1 mmol.l(-1) [9.6-15.2; 200 mg.dl(-1) (173-274)], and normoglycemia (<8 mmol.l(-1); <144 mg.dl(-1)) was reached within 5.3 h (1-25) with an overall treatment duration of 27 h (10-57). Seven hypoglycemic incidents (5 times <=2.2 mmol.l(-1); 40 mg.dl(-1), and 2 times <1.7 mmol.l(-1); 31 mg.dl(-1)) occurred in 5 (6.7%) infants, without severe clinical signs. Three hypoglycemic incidents were directly explained due to a protocol violation. One hypoglycemic incident occurred with the onset of sepsis, while no apparent cause was identified for three hypoglycemic incidents. CONCLUSIONS: Our glucose protocol was effective, but hypoglycemia occurred more frequently than in older children reported previously. Potential differences in glucose and insulin metabolism in term neonates appear to justify additional safety approaches, while awaiting further studies assessing the benefits of tight glucose protocols in this population. Meanwhile, we have decreased the initial insulin starting doses in our protocol. PMID- 22085890 TI - Subterranean termite open-air foraging and tolerance to desiccation: Comparative water relation of two sympatric Macrotermes spp. (Blattodea: Termitidae). AB - The foraging patterns of termites are strongly related to physiological limits in overcoming desiccation stress. In this study, we examined moisture preferences and physiological characteristics of Macrotermes carbonarius (Hagen) and M. gilvus (Hagen) as both exhibit conspicuous patterns of foraging activity. Despite both species showing no significant differences in calculated cuticular permeability, and percentage of total body water, they differed greatly in rate of water loss and surface area to volume ratio. For example, M. carbonarius which had a lower surface area to volume ratio (29.26-53.66) showed lower rate of water loss and percentage of total body water loss. This also resulted in higher LT(50) when exposed to extreme conditions (~2% RH). However, contrasting observations were made in M. gilvus that has smaller size with higher surface area to volume ratio of 40.28-69.75. It is likely that the standard equation for calculating insect surface areas is inadequate for these termite species. The trend was further supported by the result of a moisture preference bioassay that indicated M. carbonarius had a broader range of moisture preference (between 5% and 20%) than M. gilvus which had a relatively narrow moisture preference (only 20%). These results explain why M. carbonarius can tolerate desiccation stress for a longer period foraging above-ground in the open air; while M. gilvus only forages below ground or concealed within foraging mud tubes. PMID- 22085893 TI - Management of bedridden patients during an earthquake in Japan. PMID- 22085895 TI - A nonparametric empirical Bayes framework for large-scale multiple testing. AB - We propose a flexible and identifiable version of the 2-groups model, motivated by hierarchical Bayes considerations, that features an empirical null and a semiparametric mixture model for the nonnull cases. We use a computationally efficient predictive recursion (PR) marginal likelihood procedure to estimate the model parameters, even the nonparametric mixing distribution. This leads to a nonparametric empirical Bayes testing procedure, which we call PRtest, based on thresholding the estimated local false discovery rates. Simulations and real data examples demonstrate that, compared to existing approaches, PRtest's careful handling of the nonnull density can give a much better fit in the tails of the mixture distribution which, in turn, can lead to more realistic conclusions. PMID- 22085894 TI - Immunohistochemical expression of estrogen and progesterone receptors and outcomes in patients with newly diagnosed uterine leiomyosarcoma. AB - OBJECTIVE: We assessed the IHC expression of ER and PR and their prognostic significance in uterine leiomyosarcoma (LMS). METHODS: We identified 43 "high grade" uterine LMS cases from 7/82-7/07 for whom ER/PR IHC analysis was performed at initial diagnosis at our institution. RESULTS: Disease was confined to the uterine body in 20/43 (47%). Eighteen (42%) of 43 were ER(+); 17/42 (41%) were PR(+). At last follow-up, 33 (77%) had recurred or progressed, and 23 (54%) had died. PR expression was associated with improved progression-free survival (PFS; P=0.002) and overall survival (OS; P=0.03) overall; ER expression was not. After adjusting for stage, ER expression was associated with PFS (P=0.01), not OS (P=0.3), and PR expression maintained a significant association with PFS (P=0.002) and approached a significant association with OS (P=0.05). Neither ER nor PR expression was associated with outcome in cases with disease outside the uterine body. In cases with confined disease, median PFS for ER(+) or PR(+) cases was not reached compared to 16.9 months for ER(-) cases (95% CI: 8.1-25.7; P=0.03) and 13.5 months for PR(-) cases (95% CI: 5.9-21.1; P=0.001). Only 1/10 PR(+) cases recurred and died; 9/10 PR(-) cases recurred, and 5 died. Two of 9 ER(+) cases recurred and died; 8/11 ER(-) cases recurred, and 4 died. CONCLUSION: ER/PR expression is associated with survival outcomes in patients with high-grade uterine LMS confined to the uterine body. PR expression seems capable of identifying cases confined to the uterine body, which have better outcomes. PMID- 22085897 TI - Biomarkers in acute heart failure syndromes - are they fulfilling their promise? PMID- 22085896 TI - ARSyN: a method for the identification and removal of systematic noise in multifactorial time course microarray experiments. AB - Transcriptomic profiling experiments that aim to the identification of responsive genes in specific biological conditions are commonly set up under defined experimental designs that try to assess the effects of factors and their interactions on gene expression. Data from these controlled experiments, however, may also contain sources of unwanted noise that can distort the signal under study, affect the residuals of applied statistical models, and hamper data analysis. Commonly, normalization methods are applied to transcriptomics data to remove technical artifacts, but these are normally based on general assumptions of transcript distribution and greatly ignore both the characteristics of the experiment under consideration and the coordinative nature of gene expression. In this paper, we propose a novel methodology, ARSyN, for the preprocessing of microarray data that takes into account these 2 last aspects. By combining analysis of variance (ANOVA) modeling of gene expression values and multivariate analysis of estimated effects, the method identifies the nonstructured part of the signal associated to the experimental factors (the noise within the signal) and the structured variation of the ANOVA errors (the signal of the noise). By removing these noise fractions from the original data, we create a filtered data set that is rich in the information of interest and includes only the random noise required for inferential analysis. In this work, we focus on multifactorial time course microarray (MTCM) experiments with 2 factors: one quantitative such as time or dosage and the other qualitative, as tissue, strain, or treatment. However, the method can be used in other situations such as experiments with only one factor or more complex designs with more than 2 factors. The filtered data obtained after applying ARSyN can be further analyzed with the appropriate statistical technique to obtain the biological information required. To evaluate the performance of the filtering strategy, we have applied different statistical approaches for MTCM analysis to several real and simulated data sets, studying also the efficiency of these techniques. By comparing the results obtained with the original and ARSyN filtered data and also with other filtering techniques, we can conclude that the proposed method increases the statistical power to detect biological signals, especially in cases where there are high levels of structural noise. Software for ARSyN is freely available at http://www.ua.es/personal/mj.nueda. PMID- 22085898 TI - A comparison of ballistic and nonballistic lower-body resistance exercise and the methods used to identify their positive lifting phases. AB - This study compared differences between ballistic jump squat (B) and nonballistic back squat (NB) force, velocity, power, and relative acceleration duration, and the effect that the method used to identify the positive lifting phase had on these parameters. Ground reaction force and barbell kinematics were recorded from 30 resistance trained men during B and NB performance with 45% 1RM. Force, velocity, and power was averaged over positive lifting phases identified using the traditional peak barbell displacement (PD) and positive impulse method. No significant differences were found between B and NB mean force, and mean power, but B mean velocity was 14% greater than the NB equivalent. Positive impulse mean force was 24% greater than PD mean force, and B relative acceleration duration was 8.6% greater than the NB equivalent when PD was used to identify the end of the positive lifting phase. These results challenge common perceptions of B superiority for power development. PMID- 22085899 TI - UGT1A1 is a major locus influencing bilirubin levels in African Americans. AB - Total serum bilirubin is associated with several clinical outcomes, including cardiovascular disease, diabetes and drug metabolism. We conducted a genome-wide association study in 619 healthy unrelated African Americans in an attempt to replicate reported findings in Europeans and Asians and to identify novel loci influencing total serum bilirubin levels. We analyzed a dense panel of over two million genotyped and imputed SNPs in additive genetic models adjusting for age, sex, and the first two significant principal components from the sample covariance matrix of genotypes. Thirty-nine SNPs spanning a 78 kb region within the UGT1A1 displayed P-values <5 * 10(-8). The lowest P-value was 1.7 * 10(-22) for SNP rs887829. None of SNPs in the UGT1A1 remained statistically significant in conditional association analyses that adjusted for rs887829. In addition, SNP rs10929302 located in phenobarbital response enhancer module was significantly associated with bilirubin level with a P-value of 1.37 * 10(-11); this enhancer module is believed to have a critical role in phenobarbital treatment of hyperbilirubinemia. Interestingly, the lead SNP, rs887829, is in strong linkage disequilibrium (LD) (r(2)>=0.74) with rs10929302. Taking advantage of the lower LD and shorter haplotypes in African-ancestry populations, we identified rs887829 as a more refined proxy for the causative variant influencing bilirubin levels. Also, we replicated the reported association between variants in SEMA3C and bilirubin levels. In summary, UGT1A1 is a major locus influencing bilirubin levels and the results of this study promise to contribute to understanding of the etiology and treatment of hyperbilirubinaemia in African-ancestry populations. PMID- 22085900 TI - Severe intellectual disability and autistic features associated with microduplication 2q23.1. AB - We report on two patients with developmental delay, hypotonia, and autistic features associated with duplications of chromosome region 2q23.1-2q23.2 detected by chromosome microarray analysis. The duplications include one OMIM Morbid Map gene, MBD5, as well as seven known RefSeq genes (ACVR2A, ORC4L, EPC2, KIF5C, MIR1978, LYPD6B, and LYPD6). MBD5 lies in the minimum area of overlap of the 2q23.1 microdeletion syndrome. This report provides the first detailed clinical examination of two individuals with a duplication of this region and suggests that brain development and cognitive function may be affected by an increased dosage of the genes involved. PMID- 22085901 TI - Neolithic patrilineal signals indicate that the Armenian plateau was repopulated by agriculturalists. AB - Armenia, situated between the Black and Caspian Seas, lies at the junction of Turkey, Iran, Georgia, Azerbaijan and former Mesopotamia. This geographic position made it a potential contact zone between Eastern and Western civilizations. In this investigation, we assess Y-chromosomal diversity in four geographically distinct populations that represent the extent of historical Armenia. We find a striking prominence of haplogroups previously implicated with the Agricultural Revolution in the Near East, including the J2a-M410-, R1b1b1(*) L23-, G2a-P15- and J1-M267-derived lineages. Given that the Last Glacial Maximum event in the Armenian plateau occured a few millennia before the Neolithic era, we envision a scenario in which its repopulation was achieved mainly by the arrival of farmers from the Fertile Crescent temporally coincident with the initial inception of farming in Greece. However, we detect very restricted genetic affinities with Europe that suggest any later cultural diffusions from Armenia to Europe were not associated with substantial amounts of paternal gene flow, despite the presence of closely related Indo-European languages in both Armenia and Southeast Europe. PMID- 22085902 TI - Determination of the real effect of genes identified in GWAS: the example of IL2RA in multiple sclerosis. AB - Genome-wide association studies (GWAS), although efficient to detect genes involved in complex diseases, are not designed to measure the real effect of the genes. This is illustrated here by the example of IL2RA in multiple sclerosis (MS). Association between IL2RA and MS is clearly established, although the functional variation is still unknown: the effect of IL2RA might be better described by several SNPs than by a single one. This study investigates whether a pair of SNPs better explains the observed linkage and association data than a single SNP. In total, 522 trio families and 244 affected sib-pairs were typed for 26 IL2RA SNPs. For each SNP and pairs of SNPs, the phased genotypes of patients and controls were compared to determine the SNP set offering the best risk discrimination. Consistency between the genotype risks provided by the retained set and the identical by descent allele sharing in affected sib-pairs was assessed. After controlling for multiple testing, the set of SNPs rs2256774 and rs3118470, provides the best discrimination between the case and control genotype distributions (P-corrected=0.009). The relative risk between the least and most at-risk genotypes is 3.54 with a 95% confidence interval of [2.14-5.94]. Furthermore, the linkage information provided by the allele sharing between affected sibs is consistent with the retained set (P=0.80) but rejects the SNP reported in the literature (P=0.006). Establishing a valid modeling of a disease gene is essential to test its potential interaction with other genes and to reconstruct the pathophysiological pathways. PMID- 22085903 TI - Right ventricular dysfunction in patients with Brugada-like electrocardiography: a two dimensional strain imaging study. AB - BACKGROUND: Sodium channel blockers augment ST-segment elevation in the right precordial leads in patients undergoing Brugada-type electrocardiography (ECG). However, their effect on echocardiographic features is not known. We address this by assessing global and regional ventricular function using conventional Doppler and two- dimensional (2D) speckle tracking techniques. METHODS: Thirty-one patients with Brugada-type ECG were studied. A pure sodium channel blocker, pilsicainide, was used to provoke an ECG response. The percentage longitudinal systolic myocardial strain at the base of both the right ventricular (RV) free wall and the interventricular septum wall was measured using 2D speckle tracking. Left ventricular (LV) and RV myocardial performance (TEI) indices were also measured. RESULTS: The pilsicainide challenge provoked a positive ECG response in 13 patients (inducible group). In the inducible group, longitudinal strain was significantly reduced only at the RV (-27.3 +/- 5.4% vs -22.1 +/- 3.6%, P < 0.01), and both RV and LV TEI indices increased (RV: 0.19 +/- 0.09 vs 0.27 +/- 0.11, P < 0.05; LV: 0.30 +/- 0.10 vs 0.45 +/- 0.10, P < 0.01) after pilsicainide administration. CONCLUSIONS: Temporal and spatial analysis using the TEI index and 2D strain imaging revealed the deterioration of global ventricular function associated with conduction disturbance and RV regional function in patients with Brugada-type ECG and coved type ST elevation due to administration of a sodium channel blocker. PMID- 22085905 TI - Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo. AB - Studies of expressed genes in human heart provide insight into both physiological and pathophysiological mechanisms. This is of importance for extended understanding of cardiac function as well as development of new therapeutic drugs. Heart tissue for gene expression studies is generally hard to obtain, particularly from the ventricles. Since different parts of the heart have different functions, expression profiles should likely differ between these parts. The aim of the study was therefore to compare the global gene expression in cardiac tissue from the more accessible auricula of the right atrium to expression in tissue from the left ventricle. Tissue samples were collected from five men undergoing aortic valve replacement or coronary artery bypass grafting. Global gene expression analysis identified 542 genes as differentially expressed between the samples extracted from these two locations, corresponding to ~2% of the genes covered by the microarray; 416 genes were identified as abundantly expressed in right atrium, and 126 genes were abundantly expressed in left ventricle. Further analysis of the differentially expressed genes according to available annotations, information from curated pathways and known protein interactions, showed that genes with higher expression in the ventricle were mainly associated with contractile work of the heart. Transcription in biopsies from the auricula of the right atrium on the other hand indicated a wider area of functions, including immunity and defense. In conclusion, our results suggest that biopsies from the auricula of the right atrium may be suitable for various genetic studies, but not studies directly related to muscle work. PMID- 22085904 TI - Mammary gland morphological and gene expression changes underlying pregnancy protection of breast cancer tumorigenesis. AB - A full-term pregnancy early in life reduces lifetime risk of developing breast cancer, and the effect can be mimicked in rodents by full-term pregnancy or short term treatment with exogenous estrogen and progesterone. To gain insight into the protective mechanism, 15 3-mo-old postpubertal virgin Lewis rats were randomly assigned to three groups: control (C), pregnancy (P), or hormone (H). The P group animals underwent a full-term pregnancy, and H group animals were implanted subcutaneously with silastic capsules filled with ethynyl estradiol and megesterol acetate for 21 days. C and P animals were implanted with sham capsules. On day 21 capsules were removed, which was followed by a 49-day involution period, euthanasia, and mammary tissue collection. Global gene expression was measured using Rat Genome 230.2 Arrays. Histological analysis revealed that P and H treatments induced sustained morphological changes in the mammary gland with significantly increased percentages of mammary parenchyma and stromal tissues and higher ratio of stroma to parenchyma. Transcriptome analysis showed that P and H treatments induced sustained global changes in gene expression in the mammary gland. Analysis of commonly up- and downregulated genes in P and H relative to C treatment showed increased expression of three matrix metallopeptidases (Mmp3, 8, and 12), more differentiated mammary phenotype, enhanced innate and adaptive immunity, and reduced cell proliferation and angiogenic signatures. The sustained morphological and global gene expression changes in mammary tissue after pregnancy and hormone treatment may function together to provide the protective effect against breast cancer. PMID- 22085906 TI - Temporal changes in endometrial gene expression and protein localization of members of the IGF family in cattle: effects of progesterone and pregnancy. AB - In the study presented, the hypothesis that ligands of the insulin-like growth factor (IGF) family, as well as their binding proteins (BPs), are temporally regulated and are altered by elevated progesterone (P4) and/or pregnancy was tested. Heifers detected in standing estrus following synchronization (n = 210, day 0), were artificially inseminated (n = 140) or left as noninseminated cyclic controls (n = 70). On day 3, half of each group were randomly assigned to receive a P4-releasing intravaginal device resulting in four treatment groups, pregnant and cyclic heifers with high and normal P4 concentrations on either day 5, 7, 13, or 16 of the estrous cycle/early pregnancy. Quantitative real-time PCR and immunohistochemistry were performed on endometrial homogenate and uterine cross sections to measure transcript abundance and protein localization respectively (n = 5 per treatment per time point). No effect of day, treatment, or their interactions was observed for IGF2, IGFBP4, and -5 (P > 0.05). IGF1 and IGFBP6 expression decreased, while IGF1R and IGFBP2 expression increased (P < 0.05) as the days of the cycle or pregnancy progressed. The expression of IGFBP2 was increased by elevated P4; in addition, localization of both IGF2 and IGFBP2 protein in the luminal and superficial glandular epithelium displayed a P4 * day interaction. In conclusion it is proposed that decreased IGF1 and IGFBP6 expression with a coordinate increase in IGF1R and IGFBP2 as the estrous cycle/early pregnancy progresses, along with other factors, are required to establish a uterine environment that promotes the growth and development of the conceptus prior to implantation. In addition, the increased protein abundance of both IGF2 and IGFBP2 observed in heifers supplemented with P4 contributes to the enhanced conceptus elongation observed in this model. PMID- 22085907 TI - Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy. AB - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC-affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown. We therefore analyzed the transcriptomes of six ARVC hearts and compared our findings to six nonfailing donor hearts (NF). To characterize the ARVC-specific transcriptome, we compared our findings to samples from seven patients with idiopathic dilated cardiomyopathy (DCM). The myocardial DCM and ARVC samples were prepared from hearts explanted during an orthotopic heart transplantation representing myocardium from end-stage heart failure patients (NYHA IV). From each heart, left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, the analyses revealed no distinct expression pattern in LV and RV of myocardial ARVC samples. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only ~15-16% of the genes are commonly regulated compared with NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts. Our study is the first analysis of specific ARVC-related RV and LV gene expression patterns in terminal failing human hearts. PMID- 22085908 TI - A lateral flow biosensor for detection of nucleic acids with high sensitivity and selectivity. AB - A lateral flow biosensor based on isothermal strand-displacement polymerase reaction and gold nanoparticles has been developed for the visual detection of nucleic acids with a detection limit of 0.01 fM. PMID- 22085909 TI - The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c(6A). AB - Cytochrome c(6A) is a eukaryotic member of the Class I cytochrome c family possessing a high structural homology with photosynthetic cytochrome c(6) from cyanobacteria, but structurally and functionally distinct through the presence of a disulfide bond and a heme mid-point redox potential of +71mV (vs normal hydrogen electrode). The disulfide bond is part of a loop insertion peptide that forms a cap-like structure on top of the core alpha-helical fold. We have investigated the contribution of the disulfide bond to thermodynamic stability and (un)folding kinetics in cytochrome c(6A) from Arabidopsis thaliana by making comparison with a photosynthetic cytochrome c(6) from Phormidium laminosum and through a mutant in which the Cys residues have been replaced with Ser residues (C67/73S). We find that the disulfide bond makes a significant contribution to overall stability in both the ferric and ferrous heme states. Both cytochromes c(6A) and c(6) fold rapidly at neutral pH through an on-pathway intermediate. The unfolding rate for the C67/73S variant is significantly increased indicating that the formation of this region occurs late in the folding pathway. We conclude that the disulfide bridge in cytochrome c(6A) acts as a conformational restraint in both the folding intermediate and native state of the protein and that it likely serves a structural rather than a previously proposed catalytic role. PMID- 22085910 TI - DPOFA, a Cl-/HCO3- exchanger antagonist, stimulates fluid absorption across basolateral surface of the retinal pigment epithelium. AB - BACKGROUND: Retinal detachment is a disorder of the eye in which sensory retina separates from the retinal pigment epithelium (RPE) due to accumulation of fluid in subretinal space. Pharmacological stimulation of fluid reabsorption from subretinal space to choroid across the RPE has been suggested as a treatment strategy for retinal detachment. DPOFA, (R)-(+)-(5,6-dichloro 2,3,9,9a-tetrahydro 3-oxo-9a-propyl-1H-fluoren-7-yl)oxy]acetic acid, is an abandoned drug capable of inhibiting Cl-/HCO3- exchanger activity. We hypothesized that DPOFA may increase fluid absorption across basolateral surface of the RPE. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) analysis of mRNA for six different transporters that may act as Cl-/HCO3- exchangers was conducted in bovine and human RPE to confirm that RPE from two species expresses the same repertoire of Cl-/HCO3- exchanger isoforms. The degree of amino acid homology between orthologous human and bovine RPE-specific isoforms was calculated after performing protein alignments. Transport of fluid across bovine RPE-choroid explants mounted in the Ussing chamber was used to assess the ability of DPOFA to modulate fluid absorption across the RPE. RESULTS: Using RT-PCR we showed that three isoforms (SLC4A2, SLC4A3, and SLC26A6) are strongly expressed in human and bovine RPE preparations. Amino acid comparisons conducted for RPE-specific isoforms support the use of bovine RPE-choroid explants as an adequate experimental system for assessing fluid absorption activity for DPOFA. Our data is consistent with the fact that DPOFA stimulates fluid absorption across the RPE in bovine RPE-choroid explants. CONCLUSIONS: DPOFA seems to stimulate transport of water across the RPE in bovine RPE-choroid explants. Additional experiments are required to establish dose-dependent effect of DPOFA on fluid absorption in the bovine RPE-choroid experimental system. PMID- 22085911 TI - Sex differences and synchronous development of steroid receptor coactivator-1 and synaptic proteins in the hippocampus of postnatal female and male C57BL/6 mice. AB - The structure and function including synaptic plasticity of the hippocampus are deeply affected by steroids in a sex-dependant manner, these processes are believed to be mediated by steroid receptors though their coactivators. Our previous studies have reported the developmental profiles of steroid receptor coactivator-1 (SRC-1) and PSD-95 in the hippocampus of postnatal female rats and the sex-differences of SRC-1 immunoreactivities in the brain of adult mice. However, whether there are any sex differences about postnatal development of SRC 1 and synaptic proteins in the hippocampus remain unclear. In this study, we investigated the postnatal profile of SRC-1 and key synaptic protein synaptophysin (SYN), PSD-95 and GluR1 in the hippocampus of female and male mice using immunohistochemistry and Western blot. The results showed that in the female hippocampus, the highest levels of SRC-1 were detected at P14, SYN and GluR1 at P30 and PSD-95 at P60; while in the males, the highest levels of SRC-1, SYN and GluR1 were detected at P30, and PSD-95 at P60. Female hippocampus tended to have higher levels of SRC-1, SYN and GluR1 before P30 and PSD-95 before P14; while male hippocampus have higher levels of PSD-95 at P14, P60 and GluR1 at P0. Correlation analysis showed the profiles of SRC-1 were highly correlated with each synaptic protein. The above results showed that in the hippocampus, except some minor sex differences detected at some time-point examined, females and males shared similar postnatal developmental profile and SRC-1 may be deeply involved in the regulation of hippocampal synaptogenesis. PMID- 22085912 TI - PhyloChipTM microarray comparison of sampling methods used for coral microbial ecology. AB - Interest in coral microbial ecology has been increasing steadily over the last decade, yet standardized methods of sample collection still have not been defined. Two methods were compared for their ability to sample coral-associated microbial communities: tissue punches and foam swabs, the latter being less invasive and preferred by reef managers. Four colonies of star coral, Montastraea annularis, were sampled in the Dry Tortugas National Park (two healthy and two with white plague disease). The PhyloChipTM G3 microarray was used to assess microbial community structure of amplified 16S rRNA gene sequences. Samples clustered based on methodology rather than coral colony. Punch samples from healthy and diseased corals were distinct. All swab samples clustered closely together with the seawater control and did not group according to the health state of the corals. Although more microbial taxa were detected by the swab method, there is a much larger overlap between the water control and swab samples than punch samples, suggesting some of the additional diversity is due to contamination from water absorbed by the swab. While swabs are useful for noninvasive studies of the coral surface mucus layer, these results show that they are not optimal for studies of coral disease. PMID- 22085913 TI - Dietary sardine protein lowers insulin resistance, leptin and TNF-alpha and beneficially affects adipose tissue oxidative stress in rats with fructose induced metabolic syndrome. AB - The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-alpha and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of alpha-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective strategy against insulin resistance and related situations. PMID- 22085915 TI - Switching ability of nitro-spiropyran on Au(111): electronic structure changes as a sensitive probe during a ring-opening reaction. AB - Spiropyran is a prototype molecular switch which undergoes a reversible ring opening reaction by photoinduced cleavage of a C-O bond in the spiropyran (SP) to the merocyanine (MC) isomer. While the electronic states and switching behavior are well characterized in solution, adsorption on metal surfaces crucially affects these properties. Using two-photon photoemission and scanning tunneling spectroscopy, we resolve the molecular energy levels on a Au(111) surface of both isomeric forms. Illumination at various wavelengths does not yield any observable switching rate, thus evidencing a very small upper limit of the quantum efficiency. Electron-induced switching from the SP to the MC isomer via generation of a negative ion resonance can be detected with a quantum yield of (2.2 +/- 0.2) * 10(-10) events/electron in tunneling spectroscopy. In contrast, the back reaction could not be observed. This study reveals that the switching properties of surface-bound molecular switches can be very different compared with free molecules, reflecting the strong influence of the interaction with the metal substrate. PMID- 22085914 TI - Combination therapy for renal cell cancer: what are possible options? AB - Antiangiogenic therapy has shown promise in the treatment of patients with renal cell carcinoma (RCC). Two classes of antiangiogenic drugs, the anti-vascular endothelial growth factor antibody bevacizumab and the tyrosine kinase inhibitors sorafenib, sunitinib and pazopanib, have shown efficacy in patients with RCC and are approved by the US Food and Drug Administration for treatment of this cancer. In practice, the clinical benefit of antiangiogenic drugs in RCC has been heterogeneous, and in patients who do respond, benefits are modest and/or short lived. To improve efficacy, combination targeted therapy has been attempted, but with either very limited additional efficacy or nontolerable toxicities. Recent advances in the molecular understanding of tumor angiogenesis and mechanism of resistance, along with the rapid development of targeted drug discovery, have made it possible to further explore novel combination therapy for RCC. PMID- 22085916 TI - Congenital parasitic infections: a review. AB - This review defines the concepts of maternal-fetal (congenital) and vertical transmissions (mother-to-child) of pathogens and specifies the human parasites susceptible to be congenitally transferred. It highlights the epidemiological features of this transmission mode for the three main congenital parasitic infections due to Toxoplasma gondii, Trypanosoma cruzi and Plasmodium sp. Information on the possible maternal-fetal routes of transmission, the placental responses to infection and timing of parasite transmission are synthesized and compared. The factors susceptible to be involved in parasite transmission and development of congenital parasitic diseases, such as the parasite genotypes, the maternal co-infections and parasitic load, the immunological features of pregnant women and the capacity of some fetuses/neonates to overcome their immunological immaturity to mount an immune response against the transmitted parasites are also discussed and compared. Analysis of clinical data indicates that parasitic congenital infections are often asymptomatic, whereas symptomatic newborns generally display non-specific symptoms. The long-term consequences of congenital infections are also mentioned, such as the imprinting of neonatal immune system and the possible trans-generational transmission. The detection of infection in pregnant women is mainly based on standard serological or parasitological investigations. Amniocentesis and cordocentesis can be used for the detection of some fetal infections. The neonatal infection can be assessed using parasitological, molecular or immunological methods; the place of PCR in such neonatal diagnosis is discussed. When such laboratory diagnosis is not possible at birth or in the first weeks of life, standard serological investigations can also be performed 8-10 months after birth, to avoid detection of maternal transmitted antibodies. The specific aspects of treatment of T. gondii, T. cruzi and Plasmodium congenital infections are mentioned. The possibilities of primary and secondary prophylaxes, as well as the available WHO corresponding recommendations are also presented. PMID- 22085917 TI - Polysaccharides as building blocks for nanotherapeutics. AB - The use of polysaccharides as building blocks in the development of nano-sized drug delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, low toxicity and low cost. In addition, the variety of physicochemical properties and the ease of chemical modifications enable the preparation of a wide array of nanoparticles. This tutorial review describes the properties of common polysaccharides, the main mechanisms for polysaccharide based-nanoparticles preparation, and provides examples from the conceptual design towards pre-clinical and clinical applications. PMID- 22085918 TI - Oral cancer awareness among dentists in Kuwait. AB - OBJECTIVES: The aim of this study was to assess oral cancer awareness among dentists in Kuwait. SUBJECTS AND METHODS: A cross-sectional survey was conducted among 200 dentists working at the Ministry of Health Dental Centers and Kuwait University Dental Center using a structured questionnaire. Dentists' knowledge about risk factors of oral cancer and about diagnostic concepts, current practices and opinions, preferred point of referral as well as interest in continuing education were assessed and the responses were analyzed. RESULTS: Of the 200 dentists surveyed, 153 responded (76.5% response rate). The mean knowledge score of the respondents was 20.6 +/- 4.0 out of a total score of 30. Thirty-five (22.9%) dentists had consistently high knowledge scores for both risk factors and diagnostic concepts. Of the 153 dentists, 132 (86.3%) were interested in obtaining further information about oral cancer. CONCLUSION: This study highlighted the need for improved knowledge and education of dental practitioners on oral cancer. PMID- 22085919 TI - Bioactive glass-based scaffolds for bone tissue engineering. AB - Originally developed to fill and restore bone defects, bioactive glasses are currently also being intensively investigated for bone tissue engineering applications. In this chapter, we review and discuss current knowledge on porous bone tissue engineering scaffolds made from bioactive silicate glasses. A brief historical review and the fundamental requirements in the field of bone tissue engineering scaffolds will be presented, followed by a detailed overview of recent developments in bioactive glass-based scaffolds. In addition, the effects of ionic dissolution products of bioactive glasses on osteogenesis and angiogenic properties of scaffolds are briefly addressed. Finally, promising areas of future research and requirements for the advancement of the field are highlighted and discussed. PMID- 22085920 TI - Advances in biogas technology. AB - Biogas technology has been practiced for over a century and is widely used in full-scale facilities in China. However, there are still many technological and economic barriers to be overcomed in its applications. Recent advances and multi disciplinary cooperations in microbiology, biochemistry, and engineering science are bringing new promises of a better understanding and control of the anaerobic digestion processes, and thus a renaissance of this technology. In particular, great progress in biogas technology has been achieved in China in the approach to larger-scale and more widespread applications. This chapter overviews the recent advances in biogas technology in China, evaluates the current challenges, and discusses the emerging technologies and future perspectives. PMID- 22085921 TI - Biodiesel from conventional feedstocks. AB - At present, traditional fossil fuels are used predominantly in China, presenting the country with challenges that include sustainable energy supply, energy efficiency improvement, and reduction of greenhouse gas emissions. In 2007, China issued The Strategic Plan of the Mid-and-Long Term Development of Renewable Energy, which aims to increase the share of clean energy in the country's energy consumption to 15% by 2020 from only 7.5% in 2005. Biodiesel, an important renewable fuel with significant advantages over fossil diesel, has attracted great attention in the USA and European countries. However, biodiesel is still in its infancy in China, although its future is promising. This chapter reviews biodiesel production from conventional feedstocks in the country, including feedstock supply and state of the art technologies for the transesterification reaction through which biodiesel is made, particularly the enzymatic catalytic process developed by Chinese scientists. Finally, the constraints and perspectives for China's biodiesel development are highlighted. PMID- 22085922 TI - Adaptive changes in renal mitochondrial redox status in diabetic nephropathy. AB - Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45days post-injection, although hyperglycemia occurs within 24h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox status in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30days and 90days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. PMID- 22085923 TI - Postoperative analysis of patients who received the Universal 2 total wrist implant system. AB - Third-generation total wrist arthroplasty devices have provided joint stability, relief from pain and increased wrist motion for patients suffering from severe arthritis. While reports of clinical follow-up appointments describe improved wrist function, the improvement in overall upper extremity function and patient perception remains a question. Therefore, the purpose of this study was to assess the upper extremity function in patients that received the Universal 2 total implant system. Eight patients participated in the complete protocol, which included testing activities of daily living as well as surveys to assess patient perception. The findings of the current study suggest that although patients exhibit motion that exceeds the needed amount, many still have a perceived disability. PMID- 22085924 TI - Culturing INS-1 cells on CDPGYIGSR-, RGD- and fibronectin surfaces improves insulin secretion and cell proliferation. AB - Rat insulinoma cells (INS-1), an immortalized pancreatic beta cell line, were cultured on low-fouling carboxymethyl-dextran (CMD) layers bearing fibronectin, the tripeptide Arg-Gly-Asp (RGD) or CDPGYIGSR, a laminin nonapeptide. INS-1 cells were non-adherent on CMD and RGE but adhered to fibronectin- and peptide-coated CMD surfaces and to tissue culture polystyrene (TCPS). On CMD bearing fibronectin and the peptides, INS-1 cells showed higher glucose-stimulated insulin secretion compared to those on TCPS, bare CMD and RGE. INS-1 cells experienced a net cell growth, with the lowest found after 7 days on CMD and the highest on fibronectin. Similarly, cells on RGD and CDPGYIGSR showed lower net growth rates than those on fibronectin. Expression of E-cadherin and integrins alphavbeta3 and alpha5 were similar between the conditions, except for alpha5 expression on fibronectin, RGD and CDPGYIGSR. Larger numbers of Ki-67-positive cells were found on CDPGYIGSR, TCPS, fibronectin and RGD. Cells in all conditions expressed Pdx1. PMID- 22085925 TI - Remineralization of artificial dentinal caries lesions by biomimetically modified mineral trioxide aggregate. AB - Fluoride-releasing restorative materials are available for remineralization of enamel and root caries. However, remineralization of dentin is more difficult than remineralization of enamel due to the paucity of apatite seed crystallites along the lesion surface for heterogeneous crystal growth. Extracellular matrix proteins play critical roles in controlling apatite nucleation/growth in collagenous tissues. This study examined the remineralization efficacy of mineral trioxide aggregate (MTA) in phosphate-containing simulated body fluid (SBF) by incorporating polyacrylic acid and sodium tripolyphosphate as biomimetic analogs of matrix proteins for remineralizing caries-like dentin. Artificial caries-like dentin lesions incubated in SBF were remineralized over a 6 week period using MTA alone or MTA containing biomimetic analogs in the absence or presence of dentin adhesive application. Lesion depths and integrated mineral loss were monitored with microcomputed tomography. The ultrastructure of baseline and remineralized lesions was examined by transmission electron microscopy. Dentin remineralization was best achieved using MTA containing biomimetic analogs regardless of whether an adhesive was applied; dentinal tubules within the remineralized dentin were occluded by apatite. It is concluded that the version of MTA employed in this study may be doped with biomimetic analogs for remineralization of unbonded and bonded artificial caries-like lesions in the presence of SBF. PMID- 22085926 TI - Wnt1/betacatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair. AB - Wnts are required for cardiogenesis but the role of specific Wnts in cardiac repair remains unknown. In this report, we show that a dynamic Wnt1/betacatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair. Acute ischaemic cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by cardiac fibroblasts in the region of injury. Following cardiac injury, the epicardium is activated organ-wide in a Wnt-dependent manner, expands, undergoes epithelial-mesenchymal transition (EMT) to generate cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces cardiac fibroblasts to proliferate and express pro-fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired cardiac function and ventricular dilatation after cardiac injury. Furthermore, disruption of Wnt/betacatenin signalling in cardiac fibroblasts impairs wound healing and decreases cardiac performance as well. These findings reveal that a pro-fibrotic Wnt1/betacatenin injury response is critically required for preserving cardiac function after acute ischaemic cardiac injury. PMID- 22085928 TI - Regulation of p53 stability and function by the deubiquitinating enzyme USP42. AB - The p53 tumour suppressor protein is a transcription factor that prevents oncogenic progression by activating the expression of apoptosis and cell-cycle arrest genes in stressed cells. The stability of p53 is tightly regulated by ubiquitin-dependent degradation, driven mainly by the ubiquitin ligase MDM2. In this study, we have identified USP42 as a DUB that interacts with and deubiquitinates p53. USP42 forms a direct complex with p53 and controls level of ubiquitination during the early phase of the response to a range of stress signals. Although we do not find a clear role for USP42 in controlling either the basal or fully activated levels of p53, the function of USP42 is required to allow the rapid activation of p53-dependent transcription and a p53-dependent cell-cycle arrest in response to stress. These functions of USP42 are likely to contribute to the repair and recovery of cells from mild or transient damage. PMID- 22085929 TI - MYBPH, a transcriptional target of TTF-1, inhibits ROCK1, and reduces cell motility and metastasis. AB - Cell migration driven by actomyosin filament assembly is a critical step in tumour invasion and metastasis. Herein, we report identification of myosin binding protein H (MYBPH) as a transcriptional target of TTF-1 (also known as NKX2-1 and TITF1), a master regulator of lung development that also plays a role as a lineage-survival oncogene in lung adenocarcinoma development. MYBPH inhibited assembly competence-conferring phosphorylation of the myosin regulatory light chain (RLC) as well as activating phosphorylation of LIM domain kinase (LIMK), unexpectedly through its direct physical interaction with Rho kinase 1 (ROCK1) rather than with RLC. Consequently, MYBPH inhibited ROCK1 and negatively regulated actomyosin organization, which in turn reduced single cell motility and increased collective cell migration, resulting in decreased cancer invasion and metastasis. Finally, we also show that MYBPH is epigenetically inactivated by promoter DNA methylation in a fraction of TTF-1-positive lung adenocarcinomas, which appears to be in accordance with its deleterious functions in lung adenocarcinoma invasion and metastasis, as well as with the paradoxical association of TTF-1 expression with favourable prognosis in lung adenocarcinoma patients. PMID- 22085927 TI - Human tRNA genes function as chromatin insulators. AB - Insulators help separate active chromatin domains from silenced ones. In yeast, gene promoters act as insulators to block the spread of Sir and HP1 mediated silencing while in metazoans most insulators are multipartite autonomous entities. tDNAs are repetitive sequences dispersed throughout the human genome and we now show that some of these tDNAs can function as insulators in human cells. Using computational methods, we identified putative human tDNA insulators. Using silencer blocking, transgene protection and repressor blocking assays we show that some of these tDNA-containing fragments can function as barrier insulators in human cells. We find that these elements also have the ability to block enhancers from activating RNA pol II transcribed promoters. Characterization of a putative tDNA insulator in human cells reveals that the site possesses chromatin signatures similar to those observed at other better characterized eukaryotic insulators. Enhanced 4C analysis demonstrates that the tDNA insulator makes long-range chromatin contacts with other tDNAs and ETC sites but not with intervening or flanking RNA pol II transcribed genes. PMID- 22085930 TI - Insights into ubiquitin-conjugating enzyme/ co-activator interactions from the structure of the Pex4p:Pex22p complex. AB - Ubiquitin-conjugating enzymes (E2s) coordinate distinct types of ubiquitination via specific E3 ligases, to a large number of protein substrates. While many E2 enzymes need only the presence of an E3 ligase for substrate ubiquitination, a number of E2s require additional, non-canonical binding partners to specify their function. Here, we have determined the crystal structure and function of an E2/co activator assembly, the Pex4p:Pex22p complex. The peroxisome-associated E2 enzyme Pex4p binds the peroxisomal membrane protein Pex22p through a binding site that does not overlap with any other known interaction interface in E2 enzymes. Pex22p association enhances Pex4p's ability to transfer ubiquitin to a substrate in vitro, and Pex22p binding-deficient forms of Pex4p are unable to ubiquitinate the peroxisomal import receptor Pex5p in vivo. Our data demonstrate that the Pex4p:Pex22p assembly, and not Pex4p alone, functions as the E2 enzyme required for Pex5p ubiquitination, establishing a novel mechanism of E2 enzyme regulation. PMID- 22085931 TI - Optimal functional levels of activation-induced deaminase specifically require the Hsp40 DnaJa1. AB - The enzyme activation-induced deaminase (AID) deaminates deoxycytidine at the immunoglobulin genes, thereby initiating antibody affinity maturation and isotype class switching during immune responses. In contrast, off-target DNA damage caused by AID is oncogenic. Central to balancing immunity and cancer is AID regulation, including the mechanisms determining AID protein levels. We describe a specific functional interaction between AID and the Hsp40 DnaJa1, which provides insight into the function of both proteins. Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. Conversely, DnaJa1, but not DnaJa2, depletion reduces AID levels, stability and isotype switching. In vivo, DnaJa1 deficient mice display compromised response to immunization, AID protein and isotype switching levels being reduced by half. Moreover, DnaJa1 farnesylation is required to maintain, and farnesyltransferase inhibition reduces, AID protein levels in B cells. Thus, DnaJa1 is a limiting factor that plays a non-redundant role in the functional stabilization of AID. PMID- 22085932 TI - UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells. AB - It has been assumed, based largely on morphologic evidence, that human pluripotent stem cells (hPSCs) contain underdeveloped, bioenergetically inactive mitochondria. In contrast, differentiated cells harbour a branched mitochondrial network with oxidative phosphorylation as the main energy source. A role for mitochondria in hPSC bioenergetics and in cell differentiation therefore remains uncertain. Here, we show that hPSCs have functional respiratory complexes that are able to consume O(2) at maximal capacity. Despite this, ATP generation in hPSCs is mainly by glycolysis and ATP is consumed by the F(1)F(0) ATP synthase to partially maintain hPSC mitochondrial membrane potential and cell viability. Uncoupling protein 2 (UCP2) plays a regulating role in hPSC energy metabolism by preventing mitochondrial glucose oxidation and facilitating glycolysis via a substrate shunting mechanism. With early differentiation, hPSC proliferation slows, energy metabolism decreases, and UCP2 is repressed, resulting in decreased glycolysis and maintained or increased mitochondrial glucose oxidation. Ectopic UCP2 expression perturbs this metabolic transition and impairs hPSC differentiation. Overall, hPSCs contain active mitochondria and require UCP2 repression for full differentiation potential. PMID- 22085933 TI - FGF signalling inhibits neural induction in human embryonic stem cells. AB - Human embryonic stem cells (hESCs) can exit the self-renewal programme, through the action of signalling molecules, at any given time and differentiate along the three germ layer lineages. We have systematically investigated the specific roles of three signalling pathways, TGFbeta/SMAD2, BMP/SMAD1, and FGF/ERK, in promoting the transition of hESCs into the neuroectoderm lineage. In this context, inhibition of SMAD2 and ERK signalling served to cooperatively promote exit from hESC self-renewal through the rapid downregulation of NANOG and OCT4. In contrast, inhibition of SMAD1 signalling acted to maintain SOX2 expression and prevent non-neural differentiation via HAND1. Inhibition of FGF/ERK upregulated OTX2 that subsequently induced the neuroectodermal fate determinant PAX6, revealing a novel role for FGF2 in indirectly repressing PAX6 in hESCs. Combined inhibition of the three pathways hence resulted in highly efficient neuroectoderm formation within 4 days, and subsequently, FGF/ERK inhibition promoted rapid differentiation into peripheral neurons. Our study assigns a novel, biphasic role to FGF/ERK signalling in the neural induction of hESCs, which may also have utility for applications requiring the rapid and efficient generation of peripheral neurons. PMID- 22085935 TI - [When the brain fails]. AB - Dementia is a progressive and fatal brain disease. Assessment and diagnosis largely take place in the primary health service. Should it be like that? PMID- 22085934 TI - The structural basis of Edc3- and Scd6-mediated activation of the Dcp1:Dcp2 mRNA decapping complex. AB - The Dcp1:Dcp2 decapping complex catalyses the removal of the mRNA 5' cap structure. Activator proteins, including Edc3 (enhancer of decapping 3), modulate its activity. Here, we solved the structure of the yeast Edc3 LSm domain in complex with a short helical leucine-rich motif (HLM) from Dcp2. The motif interacts with the monomeric Edc3 LSm domain in an unprecedented manner and recognizes a noncanonical binding surface. Based on the structure, we identified additional HLMs in the disordered C-terminal extension of Dcp2 that can interact with Edc3. Moreover, the LSm domain of the Edc3-related protein Scd6 competes with Edc3 for the interaction with these HLMs. We show that both Edc3 and Scd6 stimulate decapping in vitro, presumably by preventing the Dcp1:Dcp2 complex from adopting an inactive conformation. In addition, we show that the C-terminal HLMs in Dcp2 are necessary for the localization of the Dcp1:Dcp2 decapping complex to P-bodies in vivo. Unexpectedly, in contrast to yeast, in metazoans the HLM is found in Dcp1, suggesting that details underlying the regulation of mRNA decapping changed throughout evolution. PMID- 22085936 TI - [Biomarkers of dementia]. AB - Advances are constantly being made in research on biomarkers, but dementia ought still to be a clinical diagnosis. PMID- 22085937 TI - [Where did I put my eyeglasses?]. PMID- 22085938 TI - [Multidisciplinary treatment in stroke]. PMID- 22085939 TI - [Fear paralysis in Oslo University Hospital?]. PMID- 22085940 TI - [Something to learn from--something to learn more from?]. PMID- 22085942 TI - [New diagnostic criteria for Alzheimer disease]. PMID- 22085943 TI - Physical exertion may cause high troponin levels. AB - It is important to measure troponin levels when acute myocardial infarct is suspected. Many other factors that affect the heart can cause an increase in troponin levels, for example extreme physical exertion. Recent studies have shown that more normal physical activity can also lead to increase in troponin levels in healthy individuals. PMID- 22085944 TI - [Engagement against nuclear weapons]. PMID- 22085945 TI - [Too good to be true]. PMID- 22085946 TI - Commercialization of organs. AB - The traders are on their way. We should allow the sale of organs. A strictly regulated market for organs can ensure a fair distribution of organs and proper treatment of the donor. Is this true? PMID- 22085947 TI - Low prevalence of Mycoplasma genitalium in patients examined for Chlamydia trachomatis. AB - BACKGROUND: There is increasing interest in Mycoplasma genitalium as a sexually transmissible pathogen. The clinical picture resembles that of Chlamydia trachomatis infection, but the natural course has not yet been well defined. There are no guidelines regarding who should be examined for M. genitalium. Most of the prevalence studies have been carried out in patients attending clinics for sexually transmissible diseases. We have examined the prevalence in samples sent from general practice requesting analysis for C. trachomatis. MATERIAL AND METHOD: During the period October 1 to December 31 2010, all samples sent to Molde Hospital, Norway, that queried C. trachomatis were examined also for M. genitalum. Both agents were examined using real time PCR. The PCR for C. trachomatis was performed using a CE labelled and IVD approved method from Roche. The PCR for M. genitalium was performed using an in-house method where the target gene is GAP. RESULT: A total of 950 patients were examined (Men n=225, women n=725). The prevalences of M. genitalium and C. trachomatis were 2.0 % and 10.0 % respectively (men 4.0 % and 15.1 %, women 1.4 % and 8.4 %). CONCLUSION: Because of the low prevalence, we recommend selection of patients for examination for M. genitalium. The difference in prevalence between the sexes can reflect different indications for sample taking. PMID- 22085948 TI - [Biomarkers in spinal fluid of patients with dementia]. AB - BACKGROUND: We wanted to assess whether biomarkers abeta42, tau and p-tau could differentiate between Alzheimer's disease and other dementia illnesses. MATERIAL AND METHODS: Following systematic Pubmed searches, 25 articles which reported sensitivity and specificity for Alzheimer's disease and other dementias were included. RESULTS: Most studies showed significant differences for all three markers between Alzheimer's disease and other dementia illnesses, except abeta42 which did not differ between Alzheimer's disease and dementia with Lewy bodies. Alzheimer's disease was distinguished from vascular dementia with sensitivities and specificities 77 % - 87 % and 62-80 % (abeta42); 79-100 % and 14-100 % (tau); and 78-80 % and 63-96 % (p-tau181). Alzheimer's disease and dementia with Lewy bodies were differentiated by tau and p-tau181 with sensitivities and specificities of 72-94 % and 53-92 %, and of 68-85 % and 61-85 %. Markers separated Alzheimer's disease from frontal lobe dementia with sensitivities and specificities of 37-91 % and 59-92 % (abeta42), 58-88 % and 68-92 % (tau) and 44 91 % and 79-100 % (p-tau181). INTERPRETATION: Methodological weaknesses impede the interpretation. CSF markers are not yet sufficient to differentiate between Alzheimer's disease and other forms of dementia. PMID- 22085949 TI - Cardiotoxic effects of trastuzumab. AB - BACKGROUND: Breast cancer with overexpression of the HER2 receptor is an aggressive type of breast cancer with poor prognosis. Trastuzumab (Herceptin) is a monoclonal antibody that binds to the HER2 receptor on the cell surface blocking the signals that promote cell-growth proliferation. Trastuzumab treatment has almost halved the risk of relapse, when given as an adjuvant, and has improved the overall survival in metastatic breast cancer. However, when given alone or in combination with cardiotoxic chemotherapy, especially anthracyclines, trastuzumab may lead to congestive heart failure of varying severity. MATERIAL AND METHODS: The article is a non-systematic review of articles from clinical trails, basic research, and recommendations by Norwegian and international expert panels. RESULTS: The cardiotoxic effects of trastuzumab and anthracycline in combination were already reported in the pivotal trials. Over ten years of research have revealed the mechanisms of cardiotoxicity with trastuzumab. Risk factors have been identified and recommendations drawn up for cardiac surveillance and treatment of patients with signs of heart failure. By following these recommendations the incidence of heart failure is reduced to approximately five per cent of treated patients. CONCLUSION: In summary, the favourable effects of trastuzumab are convincing, but cardiotoxicity is a significant challenge in treatment. Risk factors for side effects indicate extra vigilance, but the side effects are unpredictable and all patients treated with trastuzumab must undergo regular cardiac surveillance. PMID- 22085950 TI - [Glaucoma following lightning]. PMID- 22085951 TI - [Drug treatment of depression in children and adolescents]. AB - Antidepressants may increase suicidal behaviour in children and adolescents with depression, and should be used with great care. The article provides an overview of research that may guide the clinician when treating depression in young people. No medication should be given without a thorough evaluation of diagnoses and psychosocial problems. Psychoeducation and psychotherapy should be tried before medication is started. Fluoxetine is the first choice for depression. If it is not effective, a switch to another SSRI may prove effective. SSRIs are found to be more efficacious in adolescents than in children. PMID- 22085952 TI - [Young girl with abscesses in the face]. AB - Skin and soft tissue infections are most often caused by Staphylococcus aureus or various species of streptococcus. This case report summarizes the clinical features, diagnosis, treatment and clinical outcome of a facial infection presenting as multiple abscesses in a young and otherwise healthy girl. Nocardia brasiliensis was recovered from abscess aspiration, and treatment failure was eventually recognized for the recommended empirical antibiotic treatment, broad spectrum antibiotics and surgery. PMID- 22085953 TI - [A slow growing bacteria]. PMID- 22085954 TI - Orthopaedic surgeons in the pocket of the industry. AB - The development of new orthopaedic products depends on a close cooperation between orthopaedic surgeons and the industry. However, in recent years a number of cases of financial collusion between the industry and parts of the professional orthopaedic environment in the US have been exposed. This has highlighted the question of the extent to which orthopaedic-related research and development may have been influenced by inappropriate financial incentives. PMID- 22085955 TI - The Memory Clinic--outpatient assessment when dementia is suspected. AB - The patients who are assessed at Oslo University Hospital's Memory Clinic are young--half of them are under 65 years of age. Most are suffering from mild cognitive impairment or dementia at a very early phase while others come to get a second opinion. The assessment takes 2 - 3 hours and is conducted by a doctor and a nurse. It includes a clinical investigation, cognitive testing, an MRI scan with measurement of the medial temporal lobes, a lumbar puncture and single photon-emission tomography (SPECT of the brain). PMID- 22085958 TI - Fetal calf serum heat inactivation and lipopolysaccharide contamination influence the human T lymphoblast proteome and phosphoproteome. AB - BACKGROUND: The effects of fetal calf serum (FCS) heat inactivation and bacterial lipopolysaccharide (LPS) contamination on cell physiology have been studied, but their effect on the proteome of cultured cells has yet to be described. This study was undertaken to investigate the effects of heat inactivation of FCS and LPS contamination on the human T lymphoblast proteome. Human T lymphoblastic leukaemia (CCRF-CEM) cells were grown in FCS, either non-heated, or heat inactivated, having low (< 1 EU/mL) or regular (< 30 EU/mL) LPS concentrations. Protein lysates were resolved by 2-DE followed by phospho-specific and silver nitrate staining. Differentially regulated spots were identified by nano LC ESI Q TOF MS/MS analysis. RESULTS: A total of four proteins (EIF3M, PRS7, PSB4, and SNAPA) were up-regulated when CCRF-CEM cells were grown in media supplemented with heat inactivated FCS (HE) as compared to cells grown in media with non heated FCS (NHE). Six proteins (TCPD, ACTA, NACA, TCTP, ACTB, and ICLN) displayed a differential phosphorylation pattern between the NHE and HE groups. Compared to the low concentration LPS group, regular levels of LPS resulted in the up regulation of three proteins (SYBF, QCR1, and SUCB1). CONCLUSION: The present study provides new information regarding the effect of FCS heat inactivation and change in FCS-LPS concentration on cellular protein expression, and post translational modification in human T lymphoblasts. Both heat inactivation and LPS contamination of FCS were shown to modulate the expression and phosphorylation of proteins involved in basic cellular functions, such as protein synthesis, cytoskeleton stability, oxidative stress regulation and apoptosis. Hence, the study emphasizes the need to consider both heat inactivation and LPS contamination of FCS as factors that can influence the T lymphoblast proteome. PMID- 22085959 TI - Transcranial direct current stimulation--update 2011. AB - Non-invasive brain stimulation with weak direct currents (transcranial direct current stimulation (tDCS)) has emerged as one of the major tools to induce neuroplastic cortical excitability alterations in humans since its (re-) introduction to the arsenal of plasticity-inducing brain stimulation tools. In this review, we gather newly emerged knowledge about the effect of tDCS on brain function in both, basic and applied research. This overview will deliver an update of the last two years of research, because especially during this time numerous important studies were published covering the above-mentioned fields. PMID- 22085960 TI - A master CLOCK hard at work brings rhythm to the transcriptome. AB - In this issue of Genes & Development, Abruzzi et al. (pp. 2374-2386) use chromatin immunoprecipitation (ChIP) tiling array assays (ChIP-chip) to show that physical interactions between circadian (?24-h) clock machineries and genomes are more widespread than previously thought and provide novel insights into how clocks drive daily rhythms in global gene expression. PMID- 22085961 TI - Competition for cofactor-dependent DNA binding underlies Hox phenotypic suppression. AB - Hox transcription factors exhibit an evolutionarily conserved functional hierarchy, termed phenotypic suppression, in which the activity of posterior Hox proteins dominates over more anterior Hox proteins. Using directly regulated Hox targeted reporter genes in Drosophila, we show that posterior Hox proteins suppress the activities of anterior ones by competing for cofactor-dependent DNA binding. Furthermore, we map a motif in the posterior Hox protein Abdominal-A (AbdA) that is required for phenotypic suppression and facilitates cooperative DNA binding with the Hox cofactor Extradenticle (Exd). Together, these results suggest that Hox-specific motifs endow posterior Hox proteins with the ability to dominate over more anterior ones via a cofactor-dependent DNA-binding mechanism. PMID- 22085962 TI - An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. AB - The membrane of the primary cilium is a highly specialized compartment that organizes proteins to achieve spatially ordered signaling. Disrupting ciliary organization leads to diseases called ciliopathies, with phenotypes ranging from retinal degeneration and cystic kidneys to neural tube defects. How proteins are selectively transported to and organized in the primary cilium remains unclear. Using a proteomic approach, we identified the ARL3 effector UNC119 as a binding partner of the myristoylated ciliopathy protein nephrocystin-3 (NPHP3). We mapped UNC119 binding to the N-terminal 200 residues of NPHP3 and found the interaction requires myristoylation. Creating directed mutants predicted from a structural model of the UNC119-myristate complex, we identified highly conserved phenylalanines within a hydrophobic beta sandwich to be essential for myristate binding. Furthermore, we found that binding of ARL3-GTP serves to release myristoylated cargo from UNC119. Finally, we showed that ARL3, UNC119b (but not UNC119a), and the ARL3 GAP Retinitis Pigmentosa 2 (RP2) are required for NPHP3 ciliary targeting and that targeting requires UNC119b myristoyl-binding activity. Our results uncover a selective, membrane targeting GTPase cycle that delivers myristoylated proteins to the ciliary membrane and suggest that other myristoylated proteins may be similarly targeted to specialized membrane domains. PMID- 22085963 TI - Maelstrom coordinates microtubule organization during Drosophila oogenesis through interaction with components of the MTOC. AB - The establishment of body axes in multicellular organisms requires accurate control of microtubule polarization. Mutations in Drosophila PIWI-interacting RNA (piRNA) pathway genes often disrupt the axes of the oocyte. This results from the activation of the DNA damage checkpoint factor Checkpoint kinase 2 (Chk2) due to transposon derepression. A piRNA pathway gene, maelstrom (mael), is critical for the establishment of oocyte polarity in the developing egg chamber during Drosophila oogenesis. We show that Mael forms complexes with microtubule organizing center (MTOC) components, including Centrosomin, Mini spindles, and gammaTubulin. We also show that Mael colocalizes with alphaTubulin and gammaTubulin to centrosomes in dividing cyst cells and follicle cells. MTOC components mislocalize in mael mutant germarium and egg chambers, leading to centrosome migration defects. During oogenesis, the loss of mael affects oocyte determination and induces egg chamber fusion. Finally, we show that the axis specification defects in mael mutants are not suppressed by a mutation in mnk, which encodes a Chk2 homolog. These findings suggest a model in which Mael serves as a platform that nucleates other MTOC components to form a functional MTOC in early oocyte development, which is independent of Chk2 activation and DNA damage signaling. PMID- 22085964 TI - Drosophila CLOCK target gene characterization: implications for circadian tissue specific gene expression. AB - CLOCK (CLK) is a master transcriptional regulator of the circadian clock in Drosophila. To identify CLK direct target genes and address circadian transcriptional regulation in Drosophila, we performed chromatin immunoprecipitation (ChIP) tiling array assays (ChIP-chip) with a number of circadian proteins. CLK binding cycles on at least 800 sites with maximal binding in the early night. The CLK partner protein CYCLE (CYC) is on most of these sites. The CLK/CYC heterodimer is joined 4-6 h later by the transcriptional repressor PERIOD (PER), indicating that the majority of CLK targets are regulated similarly to core circadian genes. About 30% of target genes also show cycling RNA polymerase II (Pol II) binding. Many of these generate cycling RNAs despite not being documented in prior RNA cycling studies. This is due in part to different RNA isoforms and to fly head tissue heterogeneity. CLK has specific targets in different tissues, implying that important CLK partner proteins and/or mechanisms contribute to gene-specific and tissue-specific regulation. PMID- 22085965 TI - Heat shock reduces stalled RNA polymerase II and nucleosome turnover genome-wide. AB - Heat shock rapidly induces expression of a subset of genes while globally repressing transcription, making it an attractive system to study alterations in the chromatin landscape that accompany changes in gene regulation. We characterized these changes in Drosophila cells by profiling classical low-salt soluble chromatin, RNA polymerase II (Pol II), and nucleosome turnover dynamics at single-base-pair resolution. With heat shock, low-salt-soluble chromatin and stalled Pol II levels were found to decrease within gene bodies, but no overall changes were detected at transcriptional start sites. Strikingly, nucleosome turnover decreased genome-wide within gene bodies upon heat shock in a pattern similar to that observed with inhibition of Pol II elongation, especially at genes involved in the heat-shock response. Relatively high levels of nucleosome turnover were also observed throughout the bodies of genes with paused Pol II. These observations suggest that down-regulation of transcription during heat shock involves reduced nucleosome mobility and that this process has evolved to promote heat-shock gene regulation. Our ability to precisely map both nucleosomal and subnucleosomal particles directly from low-salt-soluble chromatin extracts to assay changes in the chromatin landscape provides a simple general strategy for epigenome characterization. PMID- 22085966 TI - The H/ACA RNP assembly factor SHQ1 functions as an RNA mimic. AB - SHQ1 is an essential assembly factor for H/ACA ribonucleoproteins (RNPs) required for ribosome biogenesis, pre-mRNA splicing, and telomere maintenance. SHQ1 binds dyskerin/NAP57, the catalytic subunit of human H/ACA RNPs, and this interaction is modulated by mutations causing X-linked dyskeratosis congenita. We report the crystal structure of the C-terminal domain of yeast SHQ1, Shq1p, and its complex with yeast dyskerin/NAP57, Cbf5p, lacking its catalytic domain. The C-terminal domain of Shq1p interacts with the RNA-binding domain of Cbf5p and, through structural mimicry, uses the RNA-protein-binding sites to achieve a specific protein-protein interface. We propose that Shq1p operates as a Cbf5p chaperone during RNP assembly by acting as an RNA placeholder, thereby preventing Cbf5p from nonspecific RNA binding before association with an H/ACA RNA and the other core RNP proteins. PMID- 22085967 TI - Reconstitution and structural analysis of the yeast box H/ACA RNA-guided pseudouridine synthase. AB - Box H/ACA ribonucleoprotein particles (RNPs) mediate pseudouridine synthesis, ribosome formation, and telomere maintenance. The structure of eukaryotic H/ACA RNPs remains poorly understood. We reconstituted functional Saccharomyces cerevisiae H/ACA RNPs with recombinant proteins Cbf5, Nop10, Gar1, and Nhp2 and a two-hairpin H/ACA RNA; determined the crystal structure of a Cbf5, Nop10, and Gar1 ternary complex at 1.9 A resolution; and analyzed the structure-function relationship of the yeast complex. Although eukaryotic H/ACA RNAs have a conserved two-hairpin structure, isolated single-hairpin RNAs are also active in guiding pseudouridylation. Nhp2, unlike its archaeal counterpart, is largely dispensable for the activity, reflecting a functional adaptation of eukaryotic H/ACA RNPs to the variable RNA structure that Nhp2 binds. The N-terminal extension of Cbf5, a hot spot for dyskeratosis congenita mutation, forms an extra structural layer on the PUA domain. Gar1 is distinguished from the assembly factor Naf1 by containing a C-terminal extension that controls substrate turnover and the Gar1-Naf1 exchange during H/ACA RNP maturation. Our results reveal significant novel features of eukaryotic H/ACA RNPs. PMID- 22085969 TI - A facile and efficient strategy for photoelectrochemical detection of cadmium ions based on in situ electrodeposition of CdSe clusters on TiO2 nanotubes. AB - An efficient protocol for selective and sensitive detection of Cd(2+) was first developed based on photocurrents obtained at CdSe clusters which are in situ electrodeposited on TiO(2) nanotubes with the gradual addition of Cd(2+), with theoretical and technical simplicity, and further successfully applied to an assay of Cd(2+) in tap and lake water samples. PMID- 22085968 TI - Evidence for evolutionary convergence at MHC in two broadly distributed mesocarnivores. AB - Variation within major histocompatibility complex (MHC) genes is important in recognizing pathogens and initiating an immune response. These genes are relevant in enhancing our understanding of how species cope with rapid environmental changes and concomitant fluctuations in selective pressures such as invasive, infectious diseases. Disease-based models suggest that diversity at MHC is maintained through balancing selection arising from the coevolution of hosts and pathogens. Despite intensive balancing selection, sequence motifs or even identical MHC alleles can be shared across multiple species; three potential mechanisms have been put forth to explain this phenomenon: common ancestry, convergent evolution, and random chance. To understand the processes that maintain MHC similarity across divergent species, we examined the variation at two orthologous MHC-DRB genes in widespread North American Musteloid species, striped skunks (Mephitis mephitis), and raccoons (Procyon lotor). These species are often sympatric and exposed to a similar suite of diseases (e.g., rabies, canine distemper, and parvovirus). Given their exposure to similar selective pressures from pathogens, we postulated that similar DRB alleles may be present in both species. Our results indicated that similar motifs are present within both species, at functionally relevant polymorphic sites. However, based on phylogenetic analyses that included previously published MHC sequences of several closely related carnivores, the respective MHC-DRB alleles do not appear to have been maintained through common ancestry and unlikely through random chance. Instead, the similarities observed between the two mesocarnivore species may rather be due to evolutionary convergence. PMID- 22085970 TI - Triggering the production of the cryptic blue pigment indigoidine from Photorhabdus luminescens. AB - The production of the blue pigment indigoidine has been achieved in the entomopathogenic bacterium Photorhabdus luminescens by a promoter exchange and in Escherichia coli following heterologous expression of the biosynthesis gene indC. Moreover, genes involved in the regulation of this previously "silent" biosynthesis gene cluster have been identified in P. luminescens. PMID- 22085971 TI - 1,3-Propanediol production and tolerance of a halophilic fermentative bacterium, Halanaerobium saccharolyticum subsp. saccharolyticum. AB - 1,3-Propanediol (1,3-PD) is widely used in polymer industry in production of polyethers, polyesters and polyurethanes. In this article, a study on 1,3-PD production and tolerance of Halanaerobium saccharolyticum subsp. saccharolyticum is presented. 1,3-PD production was optimized for temperature, vitamin B(12) and acetate concentration. The highest 1,3-PD concentrations and yields (0.6 mol/mol glycerol) were obtained at vitamin B12 concentration 64 MUg/l and an inverse correlation between 1,3-PD and hydrogen production was observed with varying vitamin B12 concentrations. In the studied temperature range and initial acetate concentrations up to 10 g/l, no significant variations were observed in 1,3-PD production. High initial acetate (29-58 g/l) was observed to cause slight decrease in 1,3-PD concentrations produced but no effects on 1,3-PD yields (mol/mol glycerol). Initial 1,3-PD concentrations inhibited the growth of H. saccharolyticum subsp. saccharolyticum. When initial 1,3-PD concentration was raised from 1g/l to 57 g/l, a decrease of 12% to 75%, respectively, in the highest optical density was observed. PMID- 22085972 TI - Apoptosis-inducing factor is involved in gentamicin-induced vestibular hair cell death. AB - AIM: Vestibular hair cell loss in response to different stimuli may be attributable to the occurrence of apoptosis, in which apoptosis-inducing factor (AIF) is an important regulator mediating apoptotic process independent of caspases. This study was designed to investigate the possible involvement of AIF in gentamicin (GM)-induced vestibular hair cell death. METHODS: Vestibular organs from postnatal day 3 or 4 rats were maintained in tissue culture and were exposed to 2 mg/ml GM for up to 72 h. Vestibular hair cell viability was quantified by MTT assay. Apoptosis was determined by flow cytometry. AIF activation was examined by RT-PCR. The expressions of the mitochondrial protein and cytoplasm protein of AIF were detected by Western blot. RESULTS: GM could significantly inhibit the cell viability of vestibular hair cells in a dose- and time-dependent manner. The number of apoptotic cells treated with GM was higher than that of cells not treated with GM. RT-PCR showed upregulation of AIF mRNA under GM. Western blot showed that AIF from mitochondria was decreased, whereas AIF from cytoplasm was increased after GM exposure. CONCLUSIONS: AIF participates in GM induced apoptosis of vestibular hair cells. PMID- 22085973 TI - High-resolution phonon study of the Ag(100) surface. AB - Using high-resolution electron energy loss spectroscopy the phonon dispersion of Ag(100) has been studied at two different sample temperatures of 86 and 300 K. The dominant feature in the spectra corresponds to the Rayleigh wave. Its full dispersion is determined along the GammaX high symmetry direction in the first and second Brillouin zones. The Rayleigh phonon maximum at the X point shows a redshift with increasing temperature. This is explained based on a surface anharmonicity with an anharmonicity constant of 0.014, comparable to the value reported for Cu(100). In the vicinity of the Gamma point two additional phonon features have been discovered at about 110 and 160 cm(-1), which are tentatively assigned to high density of states features from the bulk phonon bands. However, the observed steep dispersion is in contrast to theoretical calculations. Along GammaX two surface resonance branches have been observed with maximum frequencies in the range of 90-110 cm(-1) near to the zone boundary. These branches agree with helium atom scattering data where available, but are not predicted by theory. PMID- 22085976 TI - Fluorescence detection of single guest molecules in ultrasmall droplets of nonpolar solvent. AB - We have investigated emissive behaviours of individual perylenebisimide derivatives, N,N'-dipropyl-1,6,7,12-tetrakis(4-tert-butylphenoxy)-3,4,9,10 perylenetetra-carboxydiimide (BP-PDI), in single ultrasmall droplets of n-octane at room temperature by using confocal and wide-field microscopic techniques. Single BP-PDIs in the small droplets show no distinguishable blinking in the time courses of fluorescence intensity. This is attributed to small probabilities of the formation of the long-lived ionized state leading to the off-state of the fluorescence. Temporal change in the degree of polarization of fluorescence and wide-field fluorescence images indicated short-time adsorption of the fluorescent molecules at the interfaces between n-octane and watery environments. Fluorescence correlation spectroscopy revealed that the adsorption/desorption processes took place at least in two different time scales, probably due to the difference in the adsorption geometry and/or in the interaction, such as van der Waals interaction and hydrogen bonding, between the dye and the interface. PMID- 22085975 TI - Disentangling the myriad genomics of complex disorders, specifically focusing on autism, epilepsy, and schizophrenia. AB - Analyses of structural genome variation by array-CGH have dramatically enhanced our ability to detect copy number variations (CNVs). De novo CNVs and those co segregating with disease in a family are generally interpreted as pathogenic. Yet, often CNVs, such as recurrent microdeletions in region 15q13.3, are not so clearly pathogenic. Here we discuss potential confounding mechanisms that may lead to the phenotypic pleiotropy of CNVs, such as unmasking of recessive alleles by hemizygous deletions, interaction of CNVs with other loci and genes, genetic epistasis, allelic exclusion, and somatic mosaicism. We illustrate some of these mechanisms with a detailed analysis of recent studies of CNVs involving MCPH1, AUTS2, CNTNAP2, and mutations in GRIN2B. Next we discuss the clinical ramifications of these findings and urge workers to avoid 'diagnostic fatalism' (i.e., halting all genetic investigation after the detection of a single CNV) and address some of the future challenges likely to result from implementations of next generation sequencing techniques. PMID- 22085974 TI - TLR9 ligand CpG-ODN applied to the injured mouse cornea elicits retinal inflammation. AB - During bacterial and viral infections, unmethylated CpG-DNA released by proliferating and dying microbes is recognized by toll-like receptor (TLR) 9 in host cells, initiating innate immune responses. Many corneal infections occur secondary to epithelial breaches and represent a major cause of vision impairment and blindness globally. To mimic this clinical situation, we investigated mechanisms of TLR9 ligand-induced corneal inflammation in mice after epithelial debridement. Application of CpG oligodeoxynucleotides (ODNs) resulted in neutrophil and macrophage infiltration to the cornea and loss of transparency. By 6 hours after CpG-ODN administration, TLR9 mRNA was increased in the cornea and retina. In vivo clinical examination at 24 hours revealed inflammatory infiltrates in the vitreous and retina, which were confirmed ex vivo to be neutrophils and macrophages, along with activated resident microglia. CpG-ODN induced intraocular inflammation was abrogated in TLR9(-/-) and macrophage depleted mice. Bone marrow reconstitution of irradiated TLR9(-/-) mice with TLR9(+/+) bone marrow led to restored corneal inflammatory responses to CpG-ODN. Fluorescein isothiocyanate-CpG-ODN rapidly penetrated the cornea and ocular media to reach the retina, where it was present within CD68(+) retinal macrophages and microglia. These data show that topically applied CpG-ODN induces intraocular inflammation owing to TLR9 activation of monocyte-lineage cells. These novel findings indicate that microbial CpG-DNA released during bacterial and/or viral keratitis can cause widespread inflammation within the eye, including the retina. PMID- 22085977 TI - Reduced expression of FXYD domain containing ion transport regulator 5 in association with hypertension. AB - Experimental evidence indicates that hypertension is a multifactorial disorder and that the products of several genes may contribute to its development. The aim of this study was to investigate the expression of hypertension-related genes in spontaneous hypertensive rats (SHRs). A microarray screening for hypertension related genes was conducted in SHRs and Wistar-Kyoto (WKY) rats using total-RNA extracted from second-order mesenteric arteries and kidneys. The FXYD5 mRNA expression in vascular smooth muscle cells (VSMCs) was silenced by RNA interference (RNAi). Meanwhile, the FXYD5 mRNA overexpression in renal tubular epithelial cells (RTECs) was induced by the recombinant plasmid pcDNA3.1(+) FXYD5. The expression of FXYD5 mRNA was found to be 14.8-fold lower in SHR rats compared to that in WKY rats (P<0.01). The levels of FXYD5 mRNA expression were the highest in kidneys of SHR 13-week-old rats when the blood pressure reached the highest levels. The down-regulated FXYD5 mRNA expression inhibited the migration of smooth muscle cells (P<0.01) and cell membrane Na+-K+-ATPase activity (P<0.01). Up-regulated FXYD5 mRNA expression enhanced the renal tubular epithelial cell membrane Na+-K+-ATPase activity (P<0.05) and cell proliferation (P<0.05). FXYD5 is related to the migration of smooth muscle cells and cell membrane Na+-K+-ATPase activity in rodents. The results of the present study suggest that FXYD5 may have profound impact on the regulation of blood pressure, and that this gene may be a potential target for anti-hypertensive therapy. PMID- 22085978 TI - Effects of a 5-h hilly running on ankle plantar and dorsal flexor force and fatigability. AB - This study aimed to examine the effects of a 5-h hilly run on ankle plantar (PF) and dorsal flexor (DF) force and fatigability. It was hypothesised that DF fatigue/fatigability would be greater than PF fatigue/fatigability. Eight male trail long distance runners (42.5 +/- 5.9 years) were tested for ankle PF and DF maximal voluntary isokinetic contraction strength and fatigue resistance tests (percent decrement score), maximal voluntary and electrically evoked isometric contraction strength before and after the run. Maximal EMG root mean square (RMS(max)) and mean power frequency (MPF) values of the tibialis anterior (TA), gastrocnemius lateralis (GL) and soleus (SOL) EMG activity were calculated. The peak torque of the potentiated high- and low-frequency doublets and the ratio of paired stimulation peak torques at 10 Hz over 100 Hz (Db10:100) were analysed for PF. Maximal voluntary isometric contraction strength of PF decreased from pre- to post-run (-17.0 +/- 6.2%; P < 0.05), but no significant decrease was evident for DF (-7.9 +/- 6.2%). Maximal voluntary isokinetic contraction strength and fatigue resistance remained unchanged for both PF and DF. RMS(max) SOL during maximal voluntary isometric contraction and RMS(max) TA during maximal voluntary isokinetic contraction were decreased (P < 0.05) after the run. For MPF, a significant decrease for TA (P < 0.05) was found and the ratio Db10:100 decreased for PF (-6.5 +/- 6.0%; P < 0.05). In conclusion, significant isometric strength loss was only detected for PF after a 5-h hilly run and was partly due to low frequency fatigue. This study contradicted the hypothesis that neuromuscular alterations due to prolonged hilly running are predominant for DF. PMID- 22085979 TI - The effect of pedalling cadence on maximal accumulated oxygen deficit. AB - Pedalling cadence influences the oxygen demand and the tolerable duration of severe intensity cycle ergometer exercise. Both of these variables are factors in the calculation of maximal accumulated oxygen deficit (MAOD), which is a widely accepted measure of anaerobic capacity. We were therefore interested in determining whether pedalling cadence affected the value of MAOD. Eighteen university students performed square wave cycling tests, using cadences of 60, 80, and 100 rev min(-1), at work rates selected to cause exhaustion in ~5 min. The oxygen demands for the tests were estimated by extrapolation from the steady state oxygen uptake in two 4-min moderate intensity bouts performed using each cadence, and were greater at higher cadences. Times to exhaustion were shorter at higher cadences (368 +/- 168 s at 60 rev min(-1) > 299 +/- 118 s at 80 rev min( 1) > 220 +/- 85 s at 100 rev min(-1)). These factors conflated to produce values for MAOD that were not affected by cadence (52 +/- 5 ml kg(-1) = 52 +/- 5 ml kg( 1) = 52 +/- 5 ml kg(-1)). Similarly, the blood lactate concentrations measured 5 min post-exercise were not affected by the pedalling cadence (10.5 +/- 2.1 mM = 10.8 +/- 1.0 mM = 10.7 +/- 2.0 mM). Although muscle contraction frequency influences many exercise responses, we conclude that the expression of anaerobic capacity is not affected by the choice of pedalling cadence. PMID- 22085980 TI - NF-kappaB signaling in prostate cancer: a promising therapeutic target? AB - Prostate carcinoma (PCa) displays a wide variety of genetic alterations, versatile expression profiles as well as cell surface markers. Despite this heterogeneity, a common treatment for advanced PCa is androgen deprivation therapy (ADT). ADT targets the androgen receptor-a member of the nuclear receptor superfamily-which is required for development and function of the prostate and critical for PCa growth and survival. After an initial regression of the tumor during ADT, a large fraction of tumors progress to so-called castration-resistant prostate carcinoma (CRPca) which is highly resistant toward chemotherapy. The ensuing high mortality rates illustrate the importance of novel therapeutic targets for CRPCa. The transcription factor NF-kappaB was recently proposed as such a potential target for therapeutic intervention in CRPCa. Although NF-kappaB is essential for the regulation of innate and adaptive immunity recent data suggest a role of NF-kappaB in cancer initiation and progression. However, the exact function of NF-kappaB signaling in PCa is still a matter of debate. Here, we review known roles of NF-kappaB signaling in PCa and emphasize the crosstalk of NF-kappaB and androgen receptor signaling. Finally, we discuss potential therapeutic relevance of blocking NF-kappaB in PCa. PMID- 22085981 TI - Multiple outcomes and multiple sources of evidence: best statistical practices. PMID- 22085982 TI - Choosing methods to minimize confounding in observational studies: do the ends justify the means? PMID- 22085983 TI - Interventions for modern times: complex, collaborative, and culturally appropriate. PMID- 22085984 TI - Impact of prehospital electrocardiogram protocol and immediate catheterization team activation for patients with ST-elevation-myocardial infarction. PMID- 22085985 TI - Creating "turbo" accountable care organizations for time-critical diagnoses. PMID- 22085986 TI - Statistical analysis of noncommensurate multiple outcomes. AB - Many studies collect multiple outcomes to characterize treatment effectiveness or evaluate risk factors. These outcomes tend to be correlated because they are measuring related quantities in the same individuals, but the common approach used by researchers is to ignore this correlation and analyze each outcome separately. There may be advantages to consider the simultaneous analysis of the outcomes using multivariate methods. Although the joint analysis of outcomes measured in the same scale (commensurate outcomes) can be undertaken with standard statistical methods, outcomes measured in different scales (noncommensurate outcomes), such as mixed binary and continuous outcomes, present more difficult challenges. In this article, we contrast some statistical approaches to analyze noncommensurate multiple outcomes. We discuss the advantages of a multivariate method for the analysis of noncommensurate outcomes, including situations of missing data. A real data example from a clinical trial, comparing bare-metal with sirolimus-eluting stents, is used to illustrate the differences between the statistical approaches. PMID- 22085987 TI - Bayesian hierarchical modeling and the integration of heterogeneous information on the effectiveness of cardiovascular therapies. AB - When making therapeutic decisions for an individual patient or formulating treatment guidelines on a population level, it is often necessary to utilize information arising from different study designs, settings, or treatments. In clinical practice, heterogeneous information is frequently synthesized qualitatively, whereas in comparative effectiveness research and guideline development, it is imperative that heterogeneous data are integrated quantitatively and in a manner that accurately captures the true uncertainty in the results. Bayesian hierarchical modeling is a technique that utilizes all available information from multiple sources and naturally yields a revised estimate of the treatment effect associated with each source. A hierarchical model consists of multiple levels (ie, a hierarchy) of probability distributions that represent relationships between information arising within single populations or trials, as well as relationships between information arising from different populations or trials. We describe the structure of Bayesian hierarchical models and discuss their advantages over simpler models when multiple information sources are relevant. Two examples are presented that illustrate this technique: a meta-analysis of immunosuppressive therapy in idiopathic dilated cardiomyopathy and a subgroup analysis of the National Institute of Neurological Disorders and Stroke Intravenous Tissue Plasminogen Activator Stroke Trial. PMID- 22085988 TI - Tackling heart disease at the global level: implications of the United Nations' statement on the prevention and control of noncommunicable disease. PMID- 22085989 TI - Risk factors for injuries in alpine skiing, telemark skiing and snowboarding- case-control study. AB - BACKGROUND: Alpine skiing and snowboarding have a substantial risk of injuries, but precise risk factor estimates are limited. Objective To determine the risk factors among skiers and snowboarders. STUDY DESIGN: Case-control study. METHODS: Ski patrols reported cases (N=3277) in eight major Norwegian alpine resorts. Injury type and risk factors (age, gender, nationality, skill level, equipment, helmet use, ski school attendance, rented or own equipment) were recorded. An uninjured control group (N=2992) was obtained at the same resorts. A multivariate logistic regression analysis was used to assess the relationship between individual risk factors and risk of injury. RESULTS: The overall injury risk was increased among beginners (OR 2.72; 2.12 to 3.47), children (OR 1.72; 1.41 to 2.13), adolescents (OR 2.16; 1.72 to 2.66) and non-Nordic skiers (OR 1.80; 1.37 to 2.36). Snowboarders had a higher overall injury risk than skiers (OR 2.11; 1.81 to 2.46). Alpine skiers (OR 2.65; 1.47 to 4.80), beginners (OR 2.50; 1.61 to 3.85), children (OR 11.1; 6.7 to 20.0) and adolescents (OR 4.17; 2.44 to 7.14) were prone to lower leg fractures. Knee injuries occurred more frequently among alpine skiers (OR 1.82; 1.39 to 2.38), females (OR 1.67; 1.38 to 2.03) and beginners (OR 3.13; 2.50 to 3.85). Males (OR 1.85; 1.45 to 2.38), telemark skiers (OR 1.70; 1.30 to 2.23), children (OR 2.22; 1.37 to 3.57) and adults (OR 1.64; 1.11 to 2.37) had an increased risk for shoulder injuries. CONCLUSIONS: Snowboarders, beginners, children and adolescents had an increased injury risk. PMID- 22085990 TI - Mechanisms of injuries in World Cup Snowboard Cross: a systematic video analysis of 19 cases. AB - BACKGROUND: Snowboard cross (SBX) became an official Olympic sport in 2006. This discipline includes manoeuvring several obstacles while competing in heats. It is common for the riders to collide, making this sport both exciting and at risk of injuries. Although a recent study from the 2010 Olympic Games has shown that the injury risk was high, little is known about the injury mechanisms. OBJECTIVE: To qualitatively describe the injury situation and mechanism of injuries in World Cup Snowboard Cross. STUDY DESIGN: Descriptive video analysis. METHODS: Nineteen video recordings of SBX injuries reported through the International Ski Federation Injury Surveillance System for four World Cup seasons (2006 to 2010) were obtained. Five experts in the field of sports medicine, snowboard and biomechanics performed analyses of each case to describe the injury mechanism in detail (riding situation and rider behaviour). RESULTS: Injuries occurred at jumping (n=13), bank turning (n=5) or rollers (n=1). The primary cause of the injuries was a technical error at take-off resulting in a too high jump and subsequent flat-landing. The rider was then unable to recover leading to fall at the time of injury. Injuries at bank turn was characterised by a pattern where the rider in a balanced position lost control due to unintentional contact with another rider. CONCLUSION: Jumping appeared to be the most challenging obstacle in SBX, where a technical error at take-off was the primary cause of the injuries. The second most common inciting event was unintentional board contact between riders at bank turning. PMID- 22085991 TI - Protein-polymer nanoreactors for medical applications. AB - Major challenges that confront nanoscience in medicine today include the development of efficacious therapies with minimum side effects, diagnostic methods featuring significantly higher sensitivities and selectivities, and personalized diagnostics and therapeutics for theragnostic approaches. With these goals in mind, combining biological molecules and synthetic carriers/templates, such as polymer supramolecular assemblies, represents a very promising strategy. In this critical review, we present protein-polymer systems as reaction spaces at the nano-scale in which the enzymatic reactions take place inside polymer supramolecular assembly, at its interface with the environment or in a combination of both. The location of the protein(s) with respect to the polymer assembly generates a diversity of systems ranging from nanoreactors to active enzymatic polymer surfaces. We describe these both in terms of general modelling and addressing the specific conditions and requirements related to the medical domain. We will particularly present protein-polymer nanoreactors that provide protected spaces for enzymatic reactions. We also show how polymer supramolecular structures, such as micelles, capsules, dendrimers and vesicles, can accommodate sensitive biomolecules to mimic natural systems and functions, and to serve as avenues for new medical approaches. Even though not yet on the market, we will emphasize possible applications of protein-polymer systems that generate reaction nanospaces-as novel ways to advanced medicine (264 references). PMID- 22085992 TI - Tityus zulianus venom induces massive catecholamine release from PC12 cells and in a mouse envenomation model. AB - Scorpion envenomation is a public health problem in Venezuela, mainly produced by Tityus discrepans (TD) and Tityus zulianus (TZ). Accidents by these two species differ clinically. Thus, TZ envenomation is associated with high mortality in children due to cardiopulmonary disorders, as a result of, excessive amounts of plasma catecholamines (Epinephrine) release from adrenal medulla, probably via the voltage-gated sodium-channel activated by specific scorpion toxins. This Epi release is, in part responsible, for some of the envenomation clinical consequences, resembling those described for patients presenting catecholamine releasing tumors (pheochromocytoma). In this work, BALB/c mice and rat pheochromocytoma-derived PC12 cells were used to provide in vivo and in vitro models, respectively, on which the basis for the TZ-mediated catecholamine release mechanism could be elucidated. In mice, TZ venom increased, at 1h post injection, the Epi plasma levels in 4000%, which remained elevated for 24h. A significant rise in plasma levels of the catecholamine catabolite 3-Methoxy-4 Hydroxy-Phenyl-Glycol (MHPG) was also observed. In [(3)H]dopamine-loaded PC12 cells, TZ venom potentiated the carbamylcholine (CC)-mediated release of [(3)H]dopamine, as shown by the leftward shift in the CC-dose-response curves. Moreover, TZ venom also displayed the maximal [(3)H]dopamine releasing activity compared to TD venom, with significant reduction of the EC50 for CC. The nicotinic-acetylcholine receptor (nAChR) blocker hexamethonium induced a significant inhibition of the [(3)H]dopamine release produced by CC in PC12 cells but the TZ-elicited release of [(3)H]dopamine was 70% hexamethonium-insensitive, suggesting unidentified TZ toxins affecting other regulatory mechanisms of catecholamine secretion. PMID- 22085993 TI - Further delineation of 17p13.3 microdeletion involving CRK. The effect of growth hormone treatment. AB - Recently, a 17p13.3 microdeletion syndrome characterized by significant postnatal growth retardation, mild to moderate mental retardation and facial dysmorphic manifestations has been delineated to a small region within the area of the Miller-Dieker syndrome critical region. We report a boy with a 284 kb deletion within the Miller-Dieker critical region including CRK, but not involving YWHAE and TUSC5. He showed mental retardation and had significant postnatal growth retardation. Further, he had slight facial and limb abnormalities. Cerebral MRI, including visualization of the pituitary gland, disclosed no abnormalities. The findings in the present case indicate, that CRK may also be involved in the facial phenotype of the 17p13.3 microdeletion syndrome, and that CRK, and not YWHAE, seems to be involved in limb malformations. The effect of growth hormone treatment in CRK-deficient children is discussed. PMID- 22085994 TI - A novel homozygous 5 bp deletion in FKBP10 causes clinically Bruck syndrome in an Indonesian patient. AB - We report an Indonesian patient with bone fragility and congenital joint contractures. The initial diagnosis was Osteogenesis Imperfecta type III (OI type III) based on clinical and radiological findings. Because of (i) absence of COL1A1/2 mutations, (ii) a consanguineous pedigree with a similarly affected sibling and (iii) the existence of congenital joint contractures with absence of recessive variants in PLOD2, mutation analysis was performed of the FKBP10 gene, recently associated with Bruck syndrome and/or recessive OI. A novel homozygous deletion in FKBP10 was discovered. Our report of the first Indonesian patient with clinically Bruck syndrome, confirms the role of causative recessive FKBP10 mutations in this syndrome. PMID- 22085995 TI - 2q23.1 microdeletion of the MBD5 gene in a female with seizures, developmental delay and distinct dysmorphic features. AB - We report a 2-year-old female who initially presented with seizures, developmental delay and dysmorphic features and was found to have a 0.3 Mb deletion at chromosome 2q23.1 encompassing the critical seizure gene, MBD5. Her distinct physical features include bifrontal narrowing with brachycephaly, low anterior hairline, hypotonic facial features with short upturned nose, flat nasal bridge, hypertelorism, tented upper lip with everted lower lip, downturned corners of her mouth, and relatively coarse facial features including thickened tongue. She also had a short neck, brachytelephalangy, clinodactyly, and hypertrichosis. At 31/2 years she developed progressive ataxia and lost vocabulary at the age of 4. Regression has been reported in one other case of MBD5 deletion. MBD5 is a member of the methyl binding gene family and appears to be responsible for regulating DNA methylation in the central nervous system. Our patient was entirely deleted for the MBD5 gene with partial loss of the EPC2 gene, which suggests that haploinsufficiency of MBD5 is responsible for the distinct phenotype observed. This supports the hypothesis that MBD5 is indeed the critical gene implicated for the findings seen in patients with deletions of chromosome 2q23.1. Further studies are necessary to delineate the role that the MBD5 gene plays in the development of the brain and these specific physical characteristics. PMID- 22085997 TI - When zip codes are in short supply. PMID- 22085996 TI - Autophagy regulation by miRNAs: when cleaning goes out of service. PMID- 22085998 TI - Lateral hop movement assesses ankle dynamics and muscle activity. AB - Ankle function is frequently measured using static or dynamic tasks in normal and injured patients. The purpose of this study was to develop a novel task to quantify ankle dynamics and muscle activity in normal subjects. Twelve subjects with no prior ankle injuries participated. Video motion analysis cameras, force platforms, and an EMG system were used to collect data during a lateral hop movement task that consisted of multiple lateral-medial hops over an obstacle. Mean (SD) inversion ankle position at contact was 4.4 degrees (4.0) in the medial direction and -3.5 degrees (4.4) in the lateral direction; mean (SD) tibialis anterior normalized muscle activity was 0.11 (0.08) in the medial direction and 0.16 (0.13) in the lateral direction. The lateral hop movement was shown to be an effective task for quantifying ankle kinematics, forces, moments, and muscle activities in normal subjects. Future applications will use the lateral hop movement to assess subjects with previous ankle injuries in laboratory and clinical settings. PMID- 22085999 TI - [Mechanisms of sympathetic activity in rats exposed to different patterns of hypoxia and the correlation with blood pressure]. AB - OBJECTIVE: To observe the effects of two different hypoxia patterns on blood pressure and the underlying mechanisms. METHODS: Eighteen male SD rats were randomly divided into three groups: the intermittent hypoxia group (IH group), the continuous hypoxia group (CH group) and the normal control group (NC group). The rats of the IH and CH group were subjected to intermittent hypoxia (7 h/d) and continuous hypoxia (7 h/d) for 42 days respectively. The NC group rats were untreated. The levels of arteria caudilis systolic pressure (ACSP) were measured with noninvasive rats arteria caudilis gauge before the experiment, at the end of 3rd, 6th week of the experiment. The concentrations of norepinephrine (NE) in serum and neuropeptide Y (NPY) in plasma were respectively measured by enzyme linked-immunosorbent assay (ELISA) and radioimmunoassay. The contents of malondialdehyde (MDA) and the ability of inhibiting hydroxyl free radical in serum were analyzed by thiobarbituric acid colorimetric analysis (TBAR) at the end of 6th week. RESULTS: At the end of 3rd week, the levels of ACSP were considerably higher than those before the treatment (P<0.05). The concentrations of ACSP, NE, MDA, NPY in the IH group were significantly higher than those in the other two groups at the end of 6th week (all P<0.01). The ability of inhibiting hydroxyl free radical were decreased by the intermittent hypoxia treatment (all P<0.01). However, there was no significant difference in ACSP, NE, MDA, NPY between CH and NC group (all P>0.05). The levels of NE, NPY and MDA were positively related with ACSP (r=0.873, P<0.01; r=0.671, P<0.01; r=0.582, P<0.05). The correlation between the ability of inhibiting hydroxyl free radical and ACSP was negative (r=-0.790, P<0.01). the concentrations of MDA were positively related with NE and NPY respectively (r=0.843, 0.777, P<0.01) and the ability of inhibiting hydroxyl free radical was negatively related with NE and NPY respectively (r=-0.864, -0.717, P<0.01). CONCLUSION: Intermittent hypoxia can induce high blood pressure, which may be related to the sympathetic over-activity and the oxidative stress. PMID- 22086000 TI - Research progress in the organic cation transporters. AB - The organic cation transport systems were initially recognized in studies of renal elimination. A variety of endogenous and exogenous compounds that are harmful to the body are eliminated from the kidney via glomerular filtration and/or active tubular secretion. Among those compounds are polar organic cations that require a transporter-mediated process to cross cellular membrane and be eventually excreted into the urine. The organic cation transport systems in the kidney have been recognized for several decades. Following the insight gained from the kidney, organic cation transporters (OCTs) have also been characterized in other tissues. In particular, the OCTs in the liver and in the intestine have been proposed as important determinants of drug absorption and disposition. Over the past several decades, the mechanisms of organic cation transport have been extensively characterized using in vivo models, ex vivo organ perfusions, in vitro tissue preparations and cell lines. In particular, the molecular cloning and characterization of OCTs have remarkably increased our knowledge of this important subfamily of solute carriers. In this article, we first review the molecular cloning and characterization of OCTs. We will then describe their transport mechanisms, tissue distribution and localization, and their specificity of interaction with organic cations. Regulatory mechanisms and genetic animal models will be reviewed as they provide the most important insight on this class of transporters in recent years. Finally, we will summarize genetic variation in human OCT genes and raise clinical perspectives on these important transporters. PMID- 22086001 TI - [Expression of TMPRSS3 in the rat cochlea following kanamycin ototoxicity]. AB - OBJECTIVE: To establish the kanamycin-induced deafness model in SD rats, and to investigate the expression and significance of transmembrane protease, serine 3 (TMPRSS3) in the cochlea following kanamycin ototoxicity. METHODS: A total of 40 male SD rats were randomly divided into 4 groups. The experimental rats received intramuscular kanamycin sulfate for 3, 7, and 14 consecutive days, and the control group were treated with normal saline for 14 days. Auditory brainstem responses (ABR) were obtained before and after the kanamycin administration. The expression of TMPRSS3 in the cochlea was identified and detected by immunohistochemistry and Western blot. RESULTS: Kanamycin-induced deafness model in the SD rats was successfully established. ABR thresholds were increased and the expression of TMPRSS3 in the cochlea was reduced after the kanamycin injection (P<0.01). CONCLUSION: TMPRSS3 may play an important role in normal cochlea function and involve in the process of aminoglycoside antibiotics induced deafness. PMID- 22086002 TI - [Correlation studies between urinary retinol binding protein and renal tubular damage]. AB - OBJECTIVE: To study correlation between urinary retinol binding protein (RBP) content and renal tubular damage. METHODS: A total of 1 353 healthy people and 186 patients with renal tubular damage diagnosed by renal biopsy were enrolled. The indicators such as endogenous creatinine clearance rate (Ccr), creatinine(Cr), urinary retinol binding protein(RBP), urinary beta(2) microglobulin(beta(2)-MG), urinary N-acety1-beta-D-glucosaminidase (NAG), urine specific gravity(SG), urine osmolality of the 2 groups were examined and compared. Score of tubulointerstitial impairing and all indicators were analyzed by Spearman rank correlation analysis, and the sensitivity and specificity of indicators were calculated. RESULTS: Renal tubular damage was positively correlated with urinary RBP, beta2-MG, NAG (r=0.863, P<0.001; r=0.777, P<0.001; r=0.374, P=0.002, respectively), while negatively correlated with urine osmolaling, SG (r=-0.519, P<0.001; r=-0.624, P<0.001, respectively). The specificity and sensitivity for renal tubular damage of RBP were 91.03% and 72.06%. CONCLUSION: RBP is an idea marker for renal tubular damage, and is useful to diagnose renal tubular damage and assess the extent of the damage. PMID- 22086003 TI - [Effects of hypoxia inducible factor-1 alpha siRNA on inducible nitric oxide synthase expression in HaCaT cells]. AB - OBJECTIVE: To observe the effect of hypoxia inducible factor -1alpha (HIF-1alpha) small interfering RNA (siRNA) on the expression of HIF-1alpha and inducible nitric oxide synthase (iNOS) in HaCaT cells under hypoxia. METHODS: HaCaT cells were divided into 4 groups: the normal control group (without any treatment), the hypoxia group (under hypoxia for 24 h), the liposome control group (HaCaT cells transfected with liposome before hypoxia treatment), the RNA interference group (HaCaT cells transfected with siRNA sequences then under hypoxia for 24 h). Real time PCR and Western blot were utilized to determine HIF-1alpha and iNOS mRNA and protein expression in HaCaT cells. RESULTS: There was no significant difference of the mRNA expression of HIF-1alpha between the hypoxia group and the normoxia group (P>0.05), but the protein expressions of HIF-1alpha was increased in the hypoxic group than that in the normoxia group (P<0.05). Both the mRNA and protein expression of iNOS were increased in hypoxic conditions than that in the normoxia (P<0.05). Decreases were more significant in the mRNA and protein expression of HIF-1alpha and iNOS in the RNA interference group than that in the liposome control group in HaCaT cells (P<0.05). CONCLUSION: Hypoxia increased HIF-1alpha and iNOS expression in HaCaT cells and inhibition of HIF-1alpha expression decreased iNOS expression. PMID- 22086004 TI - Multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphism: from discovery to clinical application. AB - Multidrug resistance-associated protein 1(MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily. It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs, heavy metal anions, toxicants, and conjugates of glutathione, glucuronide and sulfate. With the advance of sequence technology, many MRP1/ABCC1 polymorphisms have been identified. Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility. In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms. In this review, we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance, toxicity, disease susceptibility and severity, prognosis prediction, and Methods to select and predict functional polymorphisms. PMID- 22086005 TI - Modulation of cardiac fibroblast function by thiazolidinediones with a focus on the role of LOX-1. AB - Cardiac fibroblasts play a pivotal role in cardiac remodeling. In response to various pro-fibrotic stimuli, such as pro-inflammatory cytokines, anoxia reoxygenation and pressure overload as well as aging, cardiac fibroblasts undergo proliferation, migration and activation, leading to the accumulation of extracellular matrix components and increased thickness and stiffness of heart. The ligands for peroxisome proliferator-activated receptor gamma, especially thiazolidinediones, modulate the function of cardiac fibroblasts and the progression of cardiac remodeling, especially under pathological conditions. Unfortunately these agents have not been found to be consistently beneficial in heart failure. Although the precise intracellular signaling pathways are not fully understood, existing evidence strongly supports the involvement of oxidative stress and related signaling pathways. Further, peroxisome proliferator activated receptor gamma and lectin-like oxidized low-density lipoprotein receptor-1 together play critical roles in thiazolidinediones-modulated cardiac fibroblast dysfunction. PMID- 22086006 TI - Effect of nicotinamide mononucleotide on insulin secretion and gene expressions of PDX-1 and FoxO1 in RIN-m5f cells. AB - OBJECTIVE: To investigate the effect of nicotinamide mononucleotide (NMN) on insulin secretion and gene expressions of pancreatic and duodenal homeobox 1(PDX 1) and forkhead box-containing protein O-1 (FoxO1), which were important transcription factors for insulin secretion. METHODS: Insulin secretion level in RIN-m5f cells was detected by rat insulin ELISA detection kit. The mRNA expression levels of PDX-1 and FoxO1 in RIN-m5f cells were analyzed by real-time PCR. The protein expression of PDX-1 was measured by Western blot. RESULTS: Insulin secretion levels in RIN-m5f cells treated with repaglinide (10 nmol/L) plus NMN (100 MUmol/L) was significantly higher than those in the blank control, the DMSO control group, and the NMN (50 MUmol/L) treated group (P<0.05). The mRNA expression levels of PDX-1 in RIN-m5f cells treated with NMN (10, 50 and 100 MUmol/L) for 36 h were significantly higher than those in the control group (P<0.05, P<0.01, and P<0.001, respectively). There was marked differences in the mRNA expression levels of PDX-1 among different concentrations of NMN (P<0.001), but no significant differences in the mRNA expression level of FoxO1 (P>0.05). No significant difference was found in the protein expression levels of PDX-1 in RIN m5f cells treated by NMN (50, 100, and 200 MUmol/L) for 36 or 48 h compared with the control group (P>0.05). CONCLUSION: NMN can stimulate insulin secretion and upregulate the mRNA expression of PDX-1 in RIN-m5f cells. PMID- 22086007 TI - Calcitonin gene-related peptide suppresses isoprenaline-induced cardiomyocyte apoptosis through regulation of microRNA-1 and microRNA-133a expression. AB - OBJECTIVE: To explore the inhibitory effect of calcitonin gene-related peptide (CGRP) on cardiomyocyte apoptosis and the underlying mechanism. METHODS: In cultured rat cardiomyocytes, apoptosis was induced by the incubation of isoprenaline (10(-5) mol/L) for 48 h. CGRP (10(-8) or 10(-7) mol/L) was administrated for 1 h before incubating isoprenaline to evaluate its effect on cardiomyocyte apoptosis. At the end of the drug treatment, the rate of apoptotic cells and intracellular reactive oxygen species (ROS) were determined, and RNA was extracted to examine the expression of microRNA-1 and microRNA-133a. RESULTS: Isoprenaline significantly increased the rate of apoptotic cells and intracellular ROS production concomitantly with the increased microRNA-1 expression and the decreased microRNA-133a expression, which were inhibited by pretreatment with CGRP. The effects of CGRP were reversed by CGRP receptor antagonist. CONCLUSION: CGRP can inhibit the isoprenaline-induced cardiomyocyte apoptosis. The beneficial effect of CGRP is related to regulating microRNA-1 and microRNA-133a expression through the prevention of isoprenaline-induced ROS production. PMID- 22086008 TI - Ischemic preconditioning protects against myocardial ischemia-reperfusion injury through inhibiting toll-like receptor 4/NF-kappaB signaling pathway in rats. AB - OBJECTIVE: To investigate whether the protection of ischemic preconditioning (IPC) against myocardial ischemia/reperfusion (I/R) injury is mediated by toll like receptor 4 (TLR4)/NF-kappaB pathway, and whether these effects are related to the release of calcitonin gene-related peptide (CGRP). METHODS: Sprague-Dawley rats were subjected to 60 min of ligation of the left anterior descending coronary artery followed by 3 h of reperfusion to induce I/R injury. IPC was performed by 4 cycles of 3-min left coronary artery occlusion followed by 5-min reperfusion before the I/R. The expression of TLR4 mRNA was determined by RT-PCR. TLR4 and NF-kappaB protein expression were analyzed by immunohistochemistry. Myocardial infarct size, CGRP concentration in plasma and activity of creatine kinase in serum were also measured. RESULTS: IPC significantly reduced the infarct size and creatine kinase activity concomitantly with the increase in plasma CGRP concentration. The expressions of TLR4 protein and mRNA and NF-kappaB protein were increased by myocardial I/R injury, and dramatically inhibited by IPC. CONCLUSION: IPC protects against myocardial I/R injury by inhibition of TLR4/NF-kappaB pathway. These effects are related to the increased the release of CGRP. PMID- 22086009 TI - Expression of scFv SA3 against hepatoma fused with enhanced green fluorescent protein and its targeted ability in vivo. AB - OBJECTIVE: To express and purify the human scFv antibody, SA3, against the hepatoma fused to enhanced green fluorescent protein, and to observe the targeted capacity of fusion protein EGFP-SA3 in vivo. METHODS: SA3 and EGFP genes were cloned into plasmid pET-25b(+) to construct the recombinant plasmid EGFP-SA3/pET 25b(+), followed by DNA sequencing. Then it was transformed into E.coli BL21(DE3) and induced for fusion expression of EGFP-SA3 with IPTG. The expressed fusion protein EGFP-SA3 was purified and detected with SDS-PAGE. HepG2 cells were incubated with the fusion protein EGFP-SA3 in vitro, and the binding bioactivity was observed under the fluorescent microscope. Further more, we injected the EGFP SA3 by caudal vein into nude mice planted by hepatoma and observed the whole body fluorescence image of EGFP. RESULTS: SA3 and EGFP genes were successfully cloned into pET-25b(+), which was confirmed by restriction enzyme NcoI-XhoI or NcoI EcoRI. A band migrated at the position 750 bp, same to EGFP gene, emerged when recombinant plasmid was digested by restriction enzyme NcoI-EcoRI. Similarly, a band, about 1 500 bp, emerged when digested by NcoI-XhoI. The open-reading frame was confirmed by DNA sequencing. Fusion protein EGFP-SA3 was expressed as inclusion body. After purification and refolding, the result of immunofluorescence detection verified that EGFP-SA3 could specifically bind to HepG2 cells and maximum tumor penetration was at 24 h after the injection. CONCLUSION: The purified fusion protein EGFP-SA3 has strong binding capacity to HepG2 cells, indicating the scFv SA3 has a potential value as a targeting molecule for diagnosis and targeted therapy for liver cancer. PMID- 22086010 TI - [Comparative proteomic analysis of hippocampus between chronic cerebral ischemia rats and normal controls]. AB - OBJECTIVE: To explore the pathogenesis of brain damage after chronic cerebral ischemia through analysis of the differences in proteins expression in hippocampus between chronic cerebral ischemia rats and normal rats. METHODS: The chronic cerebral ischemia model was established by ligating the bilateral common carotid arteries.Twenty rats were randomly divided into a model group (n=10)and a sham operation group(n=10). Four weeks later, the differences of proteins expression in hippocampus between model group and sham operation group were analyzed by two dimensional polyacryalmide gel electrophoresis and ultraflex TOF/TOF mass spectrograph. RESULTS: Compared to the sham operation group, the expressions of 4 proteins were up-regulated and that of 2 proteins were down regulated in the model group. Six proteins were identified by ultraflex TOF/TOF, which were ubiquitin carboxy-terminal hydrolase L1; Dynamin-1; TMF regulated nuclear protein-like, partial; ATP synthase; rCG50513, isoform CRA_a; and expressed sequence AU016693, isoform CRA_b. CONCLUSION: Well-resolved and reproducible 2-DE patterns of chronic cerebral ischemia rats were established. Six proteins that correlate with nerve damage after chronic cerebral ischemia are identified. PMID- 22086011 TI - [Glucose-dependent insulinotropic peptide in Type 2 diabetes after gastric bypass surgery]. AB - Glucose-dependent insulinotropic peptide (GIP), the incretins, is synthesized and released from the duodenum and proximal jejunum. Continual high-fat diet powerfully stimulated GIP secretion, leading to obesity and harmful lipid deposition in islet cells and peripheral tissues, and giving rise to insulin resistance and major disturbances in the secretion of insulin. We can improve Type 2 diabetes by compromising GIP action. The exclusion of proximal small intestine and reduction of GIP secretion may be the important reasons for Type 2 diabetes after gastric bypass surgery. PMID- 22086012 TI - [Academic misconduct of graduates and the credit education]. AB - Nowadays the phenomenon of academic misconduct (such as plagiarism, fabrication, falsification, etc.) is very frequent. The reasons for academic misconduct are involved in the problems in graduate education system, social environment and students themselves. Therefore, colleges and universities should place great emphasis on constructing a healthy school environment and academic atmosphere for failure tolerance with the help of high-tech modern means. It also needs to improve the academic supervision and evaluation system, strengthen the punishments for academic misconduct and enhance the mentor's exemplary role in education. The eventual goal for our education is to obtain innovative talents who are integrity, respect science and truth, and are good samples for academic performances. PMID- 22086013 TI - Impact of retinol binding protein 4 polymorphism on rosiglitazone response in Chinese type 2 diabetic patients. AB - OBJECTIVE: To explore the association between rs3758539G-803A and rs10882283T 179G polymorphism of retinol binding protein 4 (RBP4) and rosiglitazone response in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 472 Chinese T2DM patients and 198 healthy subjects were enrolled to identify G-803A and T-179G genotypes using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two T2DM patients with different G 803A or T-179G genotypes were selected to undergo a 12-week rosiglitazone treatment (4 mg/d). Serum fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting serum insulin (FINS), glycated hemoglobin (HbAlc), postprandial serum insulin (PINS), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after the rosiglitazone treatment. RESULTS: T2DM patients with RBP4 G-803A GG genotype showed lower TG and LDL-c concentrations compared with that in the GA+AA genotype subjects. T2DM patients with RBP4 T-179G TT genotype showed lower waist-to-hip ratio (WHR), FPG and FINS values compared with that in the TG+GG genotype individuals. Patients with GG genotype of RBP4 G-803A had an enhanced rosiglitazone efficacy on FPG and FINS compared with that in the GA+AA genotype group. Patients with RBP4 T-179G TG+GG genotype showed an enhanced rosiglitazone efficacy on HbAlc level compared with that in the TT genotype group. CONCLUSION: RBP4 G-803A and T-179G polymorphism might be associated with the development of T2DM and affect the therapeutic efficacy of rosignitazone in Chinese T2DM patients. PMID- 22086014 TI - [Proteomics analysis of adenosine A1 receptor agonist-induced delayed myocardial protection in rabbits]. AB - OBJECTIVE: To investigate the changes of myocardial protein expression profiles in 2-chloro-N6-cyclopentyladenosine (CCPA), an adenosine A1 receptor agonist induced delayed myocardial protection in New Zealand rabbits . METHODS: A total of 8 rabbits were randomly divided into a CCPA group (CCPA group) and a normal saline group (NS group). CCPA and NS were infused into rabbits in the CCPA group and the NS group respectively. Twenty-four hours later, the rabbits were subjected to 30 min left anterior descending coronary artery occlusion and were reperfused for 2 hours, then the ischemic zone tissues of left ventricle were sampled for proteomic analysis.A total of 12 other New Zeland rabbits were divided into a sham group (Sham group), a normal saline group (NS group) and a CCPA group (CCPA group). The expression of alphaB-crystalline, one of the differential proteins, was confirmed by Western blot. RESULTS: Analysis of two dimensional gel electrophoresis showed that the expression of 55 protein spots were different between the two groups, 17 protein spots were preliminarily identified with the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and Mascot and Expasy bioinformatics software. These proteins included stress proteins, metabolism-associated proteins, signal transduction pathway-related proteins, ionophorous proteins, immunity-associated proteins, and so on. Western blot showed that the expression of alphaB crystalline was significantly up-regulated in the CCPA group. CONCLUSION: The myocardial protein expression profiles are changed markedly in the preconditioning late phase of CCPA .The differential proteins might be involved in the delayed cardioprotection induced by CCPA. PMID- 22086015 TI - Photon-counting compressive sensing laser radar for 3D imaging. AB - We experimentally demonstrate a photon-counting, single-pixel, laser radar camera for 3D imaging where transverse spatial resolution is obtained through compressive sensing without scanning. We use this technique to image through partially obscuring objects, such as camouflage netting. Our implementation improves upon pixel-array based designs with a compact, resource-efficient design and highly scalable resolution. PMID- 22086016 TI - Detailed performance modeling of a pulsed high-power single-frequency Ti:sapphire laser. AB - Differential absorption lidar (DIAL) is a unique technique for profiling water vapor from the ground up to the lower stratosphere. For accurate measurements, the DIAL laser transmitter has to meet stringent requirements. These include high average power (up to 10 W) and high single-shot pulse energy, a spectral purity >99.9%, a frequency instability <60 MHz rms, and narrow spectral bandwidth (single-mode, <160 MHz). We describe extensive modeling efforts to optimize the resonator design of a Ti:sapphire ring laser in these respects. The simulations were made for the wavelength range of 820 nm, which is optimum for ground-based observations, and for both stable and unstable resonator configurations. The simulator consists of four modules: (1) a thermal module for determining the thermal lensing of the Brewster-cut Ti:sapphire crystal collinear pumped from both ends with a high-power, frequency-doubled Nd:YAG laser; (2) a module for calculating the in-cavity beam propagations for stable and unstable resonators; (3) a performance module for simulating the pumping efficiency and the laser pulse energy; and (4) a spectral module for simulating injection seeding and the spectral properties of the laser radiation including spectral impurity. Both a stable and an unstable Ti:sapphire laser resonator were designed for delivering an average power of 10 W at a pulse repetition frequency of 250 Hz with a pulse length of approximately 40 ns, satisfying all spectral requirements. Although the unstable resonator design is more complex to align and has a higher lasing threshold, it yields similar efficiency and higher spectral purity at higher overall mode volume, which is promising for long-term routine operations. PMID- 22086017 TI - Optimization design of diffractive phase elements for beam shaping. AB - An improved approach called the weighted YG algorithm for the design of the diffractive phase element (DPE) that implements beam shaping in the fractional Fourier transform domain and free space is presented. Modeling designs of the DPE are carried out for several fractional orders and different parameters of the beam for optimally converting a Gaussian profile into a uniform beam. We found that our algorithm can improve the beam shaping effect, reduce the error function, and increase uniformity of light intensity. PMID- 22086018 TI - Measurement based on fringe reflection for testing aspheric optical axis precisely and flexibly. AB - A method based on fringe reflection is proposed to measure the optical axis of an aspheric mirror precisely and flexibly. In the measurement, a screen displaying a fringe pattern is moved along its normal direction, and a camera is located beside and observes the fringe pattern reflected via a tested surface. This method can test the optical axis of an aspheric mirror quantitatively before measuring the absolute height of the tested surface. And it can be combined with some presented methods that need to fit the aspheric mirror according to the optical axis to measure the surface. To validate the ability of this method, it is combined with one of the presented methods to measure absolute height of an aspheric mirror precisely and flexibly. Computer simulations and preliminary experiment validate the feasibility of this method. PMID- 22086019 TI - Numerical method to optimize the polar-azimuthal orientation of infrared superconducting-nanowire single-photon detectors. AB - A finite-element method for calculating the illumination-dependence of absorption in three-dimensional nanostructures is presented based on the radio frequency module of the Comsol Multiphysics software package (Comsol AB). This method is capable of numerically determining the optical response and near-field distribution of subwavelength periodic structures as a function of illumination orientations specified by polar angle, phi, and azimuthal angle, gamma. The method was applied to determine the illumination-angle-dependent absorptance in cavity-based superconducting-nanowire single-photon detector (SNSPD) designs. Niobium-nitride stripes based on dimensions of conventional SNSPDs and integrated with ~ quarter-wavelength hydrogen-silsesquioxane-filled nano-optical cavity and covered by a thin gold film acting as a reflector were illuminated from below by p-polarized light in this study. The numerical results were compared to results from complementary transfer-matrix-method calculations on composite layers made of analogous film-stacks. This comparison helped to uncover the optical phenomena contributing to the appearance of extrema in the optical response. This paper presents an approach to optimizing the absorptance of different sensing and detecting devices via simultaneous numerical optimization of the polar and azimuthal illumination angles. PMID- 22086020 TI - Theory for the measurement of the linear and nonlinear refractive indices of double-clad fibers using an interferometric technique. AB - Multiple-beam Fizeau fringes are formed across a liquid silvered wedge when it is illuminated by a collimated beam of monochromatic light. Inserting the fiber into the liquid silvered wedge causes the fringes to shift across the fiber region with respect to the fringes at the liquid region. Fringe shift is a function in the geometry of the different regions of the fiber and the refractive index profile of the fiber. In this paper, theoretical models for the fringe shift across double-clad fibers (DCFs) with rectangular, elliptical, circular, and D shaped inner cladding are developed. An algorithm to reconstruct the linear and nonlinear terms of the refractive index profile of the DCF is outlined. Numerical examples are provided and discussed. PMID- 22086021 TI - All-optical thermo-plasmonic device. AB - We demonstrate an all-optical thermo-plasmonic effect to switch/modulate the surface plasmon resonance signal intensity excited at the metal-air interface. This optically addressed thermo-plasmonic measurement scheme is suitable to amplify very small changes in the complex dielectric constant (epsilon(m)(T)) of thin gold (Au) film, induced by the Ar(+) laser. The predominant contributions due to small but highly repeatable transient photo-thermal effects in the complex metal dielectric constant is confirmed to be the reason behind the highly reproducible all-optical thermo-plasmonic device performance presented here. PMID- 22086022 TI - Optimization of the pulse-width of diode-pumped passively Q-switched mode-locked c-cut Nd:GdVO4 laser with a GaAs saturable absorber. AB - By considering the single-photon absorption and two-photon absorption processes in the GaAs saturable absorber, the coupled rate equations for a diode-pumped passively Q-switched and mode-locked (QML) laser with GaAs coupler under Gaussian approximation are given. These rate equations are solved numerically. The key parameters of an optimally coupled passively QML laser with the shortest pulse width envelope are determined. These key parameters include the parameters of the gain medium, the saturable absorber, and the resonator, which can minimize the pulse-width of a singly Q-switched envelope. Sample calculations for a diode pumped passively Q-switched mode-locked c-cut Nd:GdVO(4) laser with a GaAs coupler are presented to demonstrate that the shortest pulse-width envelope can be obtained by selecting the optimal small-signal transmission of the saturable absorber and the reflectivity of the output mirror. PMID- 22086023 TI - Fabrication of phase masks with variable diffraction efficiency using HEBS glass technology. AB - A new fabrication method of apodized diffractive optical elements is proposed. It relies on using high energy beam sensitive glass as a halftone mask for variable diffraction efficiency phase masks generation in a resist layer. The presented technology is especially effective in mass production. Although fabrication of an amplitude mask is required, it is then repeatedly used in a single shot projection photolithography, which is much simpler and less laborious than the direct variable-dose pattern writing. Three prototypes of apodized phase masks were manufactured and characterized. The main advantages as well as limitations of the proposed technology are discussed. PMID- 22086024 TI - Laser direct writing of rotationally symmetric high-resolution structures. AB - We present a laser direct writing system for the efficient fabrication of high resolution axicon structures. The setup makes use of scanning beam interference lithography incorporated with a fringe locking scheme for tight fringe phase control and allows us to fabricate large area structures with a period down to 450 nm. PMID- 22086025 TI - High-precision diode-laser-based temperature measurement for air refractive index compensation. AB - We present a laser-based system to measure the refractive index of air over a long path length. In optical distance measurements, it is essential to know the refractive index of air with high accuracy. Commonly, the refractive index of air is calculated from the properties of the ambient air using either Ciddor or Edlen equations, where the dominant uncertainty component is in most cases the air temperature. The method developed in this work utilizes direct absorption spectroscopy of oxygen to measure the average temperature of air and of water vapor to measure relative humidity. The method allows measurement of temperature and humidity over the same beam path as in optical distance measurement, providing spatially well-matching data. Indoor and outdoor measurements demonstrate the effectiveness of the method. In particular, we demonstrate an effective compensation of the refractive index of air in an interferometric length measurement at a time-variant and spatially nonhomogeneous temperature over a long time period. Further, we were able to demonstrate 7 mK RMS noise over a 67 m path length using a 120 s sample time. To our knowledge, this is the best temperature precision reported for a spectroscopic temperature measurement. PMID- 22086026 TI - Detection of microbubble position by a digital hologram. AB - This paper reports on a new technique of measurements of microbubble position in three dimensions with high time-resolution. The technique is based on micro digital holographic particle tracking velocimetry. In this technique, an intensity profile is constructed from a holographic image of a microbubble where the profile results in showing two peaks. The distance between the two peaks appears to relate to the size of the microbubble's diameter. The three dimensional position of the bubble can be detected by the center of the two peaks and the center point of the bubble image focused by a digital hologram. We also theoretically obtained the intensity profile of a microbubble by considering a refraction of light on a bubble surface to a ring-shaped aperture model. The theoretically obtained distance between the two peaks is found to be in good agreement with the values obtained experimentally. PMID- 22086027 TI - Temperature-dependent index of refraction of monoclinic Ga2O3 single crystal. AB - We present temperature-dependent refractive index along crystallographic b[010] and a direction perpendicular to (100)-plane for monoclinic phase (beta) Ga(2)O(3) single crystal grown by the optical floating zone technique. The experimental results are consistent with the theoretical result of Litimein et al.1. Also, the Sellmeier equation for wavelengths in the range of 0.4-1.55 MUm is formulated at different temperatures in the range of 30-175 degrees C. The thermal coefficient of refractive index in the above specified range is ~10(-5)/ degrees C. PMID- 22086028 TI - Estimation of wavelength difference using scale adjustment in two-wavelength digital holographic interferometry. AB - We propose a method for an estimation of wavelength difference using scale adjustment in two-wavelength digital holographic interferometry. To estimate wavelength difference, two holograms recorded with different wavelengths are reconstructed on the basis of the Fresnel diffraction integral, and pixel sizes in the reconstruction plane, which depend on the wavelength in recording hologram, are analyzed. In the analysis, a zero-padding method and an intensity correlation function are used to adjust pixel sizes in the reconstruction plane and then obtain a wavelength difference given by a difference between the pixel sizes. Theoretical predictions and experimental results are shown to indicate the usefulness of the proposed method in this paper. PMID- 22086029 TI - Single-channel color image encryption using a modified Gerchberg-Saxton algorithm and mutual encoding in the Fresnel domain. AB - A single-channel color image encryption is proposed based on the modified Gerchberg-Saxton algorithm (MGSA) and mutual encoding in the Fresnel domain. Similar to the double random phase encoding (DRPE), this encryption scheme also employs a pair of phase-only functions (POFs) as encryption keys. But the two POFs are generated by the use of the MGSA rather than a random function generator. In the encryption process, only one color component is needed to be encrypted when these POFs are mutually served as the second encryption keys. As a result, a more compact and simple color encryption system based on one-time-pad, enabling only one gray cipheretext to be recorded and transmitted when holographic recording is used, is obtained. Moreover, the optical setup is lensless, thus easy to be implemented and the system parameters and wavelength can be served as additional keys to further enhance the security of the system. The feasibility and effectiveness of the proposed method are demonstrated by numerical results. PMID- 22086030 TI - Gas Raman sensing with multi-opened-up suspended core fiber. AB - Gas sensing and fluid-guiding response properties of a suspended core fiber Raman analyzer with side-opened and strut microfluid-guiding array are explored. A Raman sensing model is introduced for effective mode area optimization and normalized intensity overlap enhancement between Raman sensing light and analyte. Calculations predict that there is a trade-off between the overlap and the effective mode area, while the optimal trade-off depends on the refractive index of the background material, core diameter, and strut's thickness. Furthermore, the multi-opened-up structure ensures a fast gases diffusing into/out of each hole for real-time Raman sensing. Simulation results confirm a limited gas sensing response time of less than 6 s could be feasible and, thus, a new approach to real-time gas sensing applications is identified. PMID- 22086031 TI - Direct observation of plasmonic index ellipsoids on a deep-subwavelength metallic grating. AB - We constructed a metallic grating on a deep-subwavelength scale and tested its plasmonic features in visible frequencies. The deep-subwavelength metallic grating effectively acts as an anisotropic homogeneous uniaxial form-birefringent metal, exhibiting different optical responses for polarizations along different optical axes. Therefore, this form-birefringent metal supports anisotropic surface plasmon polaritons that are characterized by directly imaging the generated plasmonic index ellipsoids in reciprocal space. The observed plasmonic index ellipsoids also show a rainbow effect, where different colors are dispersively distributed in reciprocal space. PMID- 22086032 TI - Dynamic switching of the chiral beam on the spiral plasmonic bull's eye structure [Invited]. AB - A polarization-dependent switchable plasmonic beaming structure composed of metallic hole surrounded by double spiral dielectric gratings is proposed. The main mechanism of the proposed structure is based on the angular momentum change of surface plasmon caused by the spiral geometry. On- and off-states of the proposed device are determined by the condition whether the rotating direction of incident polarization is the same as or opposite of the direction of the spiral rotations. Qualitative analytical expressions of the switching mechanisms and full-vectorial numerical results are presented. PMID- 22086033 TI - Influence of film thickness on the optical transmission through subwavelength single slits in metallic thin films. AB - Silver and gold films with thicknesses in the range of 120-450 nm were evaporated onto glass substrates. A sequence of slits with widths varying between 70 and 270 nm was milled in the films using a focused gallium ion beam. We have undertaken high-resolution measurements of the optical transmission through the single slits with 488.0 nm (for Ag) and 632.8 nm (for Au) laser sources aligned to the optical axis of a microscope. Based on the present experimental results, it was possible to observe that (1) the slit transmission is notably affected by the film thickness, which presents a damped oscillatory behavior as the thickness is augmented, and (2) the transmission increases linearly with increasing slit width for a fixed film thickness. PMID- 22086034 TI - Slow pulses in disordered photonic-crystal waveguides. AB - Using a 3D fully-vectorial coupled Bloch-mode method, we present a systematic study of the transport of slow-light pulses in single-mode photonic-crystal waveguides (PhCW) with a realistic disorder model. For the intermediate regime corresponding to waveguide lengths of the order of the mean-free path (3 dB attenuation), we show that the group-velocity has a strong impact on the pulse broadening and distortion, limiting the practical use of PhCW to group indices below ~50. For smaller group velocities, the pulse experiences an additional delay and the group-velocity is no longer a meaningful quantity. PMID- 22086035 TI - Experimental study on polarization lens formed by asymmetrical metallic hole array. AB - A polarization bifocal lens based on the polarization effect caused by asymmetrical hole arrays had been designed, fabricated, and characterized experimentally. By considering the fact that the skin depth of an infrared electromagnetic field inside metal is much shorter than the incident wavelength, a polarization bifocal lens composed of high deep-width ratio metallic holes was realized by using a gold-coated silicon structure to replace the one directly formed on a thick metal film. An infrared optical experiment setup is built based on the secondary imagery method for characterizing the focal length of the designed bifocal lens. The measured focal lengths of the fabricated bifocal lens coincide well with the designed values, which proves the validity for realizing the polarization elements with the proposed structure and the feasibility of the fabrication process. PMID- 22086036 TI - Surface-enhanced fluorescence from silver fractallike nanostructures decorated with silver nanoparticles. AB - Fluorescence emission of fluorophore molecules in the close vicinity of a nanostructured metal surface can be enhanced through a local electromagnetic field with the help of surface plasmon resonance. The fluorescence enhancement effect is very sensitive to the topography and dielectric property of the metal substrate. In the current work, metal substrates with complex structures, which are made of silver fractallike structures and nanoparticles (NPs), are prepared through electrochemical reduction followed by physical deposition. The surface enhanced fluorescence of Rhodamine 6G monolayer molecules deposited on the prepared complex substrates are investigated with the laser spectroscopic technique. The experimental results show that the fractallike structure decorated with silver NPs presents stronger fluorescence enhancement, compared with silver NPs or pure silver fractallike structures. PMID- 22086037 TI - Enhancing the lateral photovoltaic effect by coating the absorbing film on metal oxide-semiconductor structure. AB - By coating with a carbon film and graphene sheet (GS) on position-sensitive detectors based on the metal-oxide-semiconductor structure, sensitivity, linearity, and saturation power are significantly improved. We attribute this enhancement of absorptivity to lasers. The improvement effect of carbon film is more obvious than that of GS coating because of GS's high conductivity. PMID- 22086038 TI - Subwavelength imaging of a multilayered superlens with layers of nonequal thickness. AB - We propose a multilayered superlens comprising alternately layered metal and dielectric films with layers of nonequal thickness to realize subwavelength imaging, even when permittivities of the metal and dielectric are mismatched. Based on ideal imaging conditions, the exact constraint relations about the thickness of each dielectric layer and the permittivity of the surrounding medium of the multilayered superlens are first acquired when the superlens is modeled by the effective medium theory. Theoretical analysis and numerical simulations indicate that a multilayered superlens with constraint relations can realize subwavelength imaging at wavelengths of 335 to 385 nm. PMID- 22086039 TI - White light-emitting diode coated with ZnSe:Mn/ZnSe nanocrystal films enveloped by SiO2. AB - Mn-doped nanocrystals (NCs) have attracted much attention for their excellent properties. In our work, colloidal Mn-doped NCs with high quantum yield are synthesized and enveloped with silica hydrosol. The blend of NCs and silica hydrosol is coated on a blue light-emitting diode (LED), and the appropriate thickness of the NC film is found. White light is gained through the mix of the blue emission of the LED and the orange emission from Mn-doped NC films. The chromaticity coordinates and the image of the white LED indicate that Mn-doped NCs can be a good substitute for YAG:Ce phosphor, and the reliability of the white LED can be improved by enveloping NCs with SiO(2). PMID- 22086040 TI - Circular Fibonacci gratings. AB - We introduce circular Fibonacci gratings (CFGs) that combine the concept of circular gratings and Fibonacci structures. Theoretical analysis shows that the diffraction pattern of CFGs is composed of fractal distributions of impulse rings. Numerical simulations are performed with two-dimensional fast Fourier transform to reveal the fractal behavior of the diffraction rings. Experimental results are also presented and agree well with the numerical results. The fractal nature of the diffraction field should be of great theoretical interest, and shows potential to be further developed into practical applications, such as in laser measurement with wideband illumination. PMID- 22086041 TI - Ferrodispersion: a promising candidate for an optical capacitor. AB - A ferrodispersion, which comprises micrometer-sized magnetizable spheres dispersed in a ferrofluid, is shown to store retrievable optical energy. It is observed that when such dispersion is subjected to a transverse magnetic field and a linearly polarized monochromatic light with its electric vector perpendicular to the applied field is incident on it, then for a critical static magnetic field of moderate intensity the emerging light disappears. Upon removing the light and then switching off the field, again light of the same frequency and same state of polarization reappears. A time delay between emission of the light and switching off the field is observed. The statistical distribution of this delay is reported. Intensity of the retrieval signal is found to depend on the storage time. This effect is investigated. Storing and retrieval of optical energy will be useful for developing a magnetically tunable optical capacitor. PMID- 22086042 TI - Fast photovoltaic effects tuned by vicinal interface microstructure in manganite based all-perovskite-oxide heterojunctions. AB - Interfacial microstructure tunable photovoltaic effects have been reported in heterojunctions of La(1-x)Ca(x)MnO(3) thin films and tilted or exact cut Nb-doped SrTiO(3) single crystal substrates under irradiation of UV pulsed laser. The photoresponse times of vicinal junctions and films were obviously faster than those of exact cut samples. The behaviors can be explained by the slope of the built-in electric field in the 10 degrees tilted heterojunction and the interfacial terrace microstructure of La(1-x)Ca(x)MnO(3) films. PMID- 22086043 TI - Subwavelength focusing using a hyperbolic medium with a single slit. AB - A hyperbolic dispersion medium with a planar surface that can be used for subwavelength focusing is proposed. By combining the hyperbolic medium in a single slit with diffraction limit width, a laser beam could be focused to a subwavelength spot in the near field. Compared to a conventional superlens, the subdiffraction focusing in this work has higher optical throughput. Using a planar hyperbolic medium, which is actually alternating silver/dielectric multilayers, we showed that the focusing resolution of the designed device is down to ~lambda/5 using green light illumination (at a wavelength of 514.5 nm). PMID- 22086044 TI - Hyperbranched CdTe nanostructures via a self-assembly route: optical properties. AB - In this work, we report a luminescent nanobundle structure formed by a hierarchical self-assembly process of thioglycolic acid (TGA)-capped CdTe quantum dots (QDs). The luminescence intensity of CdTe nanostructures is high enough to get a clear one-photon excitation confocal image. High contrast two-photon excitation confocal images suggest that the nonlinear properties of pristine QDs are well inherited by the formed CdTe nanostructures. The controllability of the structures and inheritance of the optical properties of the building units make the self-assembled nanostructures new generation materials. PMID- 22086045 TI - Largely extended light-emission shift of ZnSe nanostructures with temperature. AB - ZnSe nanowires and nanobelts with zinc blende structure have been synthesized. The morphology and the growth mechanisms of the ZnSe nanostructures will be discussed. From the photoluminescence (PL) of the ZnSe nanostructures, it is interesting to note that red color emission with only a single peak at the photon energy of 2 eV at room temperature is obtained while the typical bandgap transition energy of ZnSe is 2.7 eV. When the temperature is reduced to 150 K, the peak wavelength shifts to 2.3 eV with yellowish emission and then blue emission with the peak at 2.7 eV at temperature less than 50 K. The overall wavelength shift of 700 meV is obtained as compared to the conventional ZnSe of about 100 meV (i.e., sevenfold extension). The ZnSe nanostructures with enhanced wavelength shift can potentially function as visible light temperature-indicator. The color change from red to yellowish and then to blue is large enough for the nanostructures to be used for temperature-sensing applications. The details of PL spectra of ZnSe at various temperatures are studied from (i) the spectral profile, (ii) the half-width half-maximum, and (iii) the peak photon energy of each of the emission centers. The results show that the simplified configuration coordinate model can be used to describe the emission spectra, and the frequency of the local vibrational mode of the emission centers is determined. PMID- 22086046 TI - Nanoscale ridge aperture as near-field transducer for heat-assisted magnetic recording. AB - Near-field transducer based on nanoscale optical antenna has been shown to generate high transmission and strongly localized optical spots well below the diffraction limit. In this paper, nanoscale ridge aperture antenna is considered as near-field transducer for heat-assisted magnetic recording. The spot size and transmission efficiency produced by ridge aperture are numerically studied. We show that the ridge apertures in a bowtie or half-bowtie shape are capable of generating small optical spots as well as elongated optical spots with desired aspect ratios for magnetic recording. The transmission efficiency can be improved by adding grooves around the apertures. PMID- 22086047 TI - Scattering characterization of nanopigments in metallic coatings using hyperspectral optical imaging. AB - We have determined the reflectance spectra of colored metallic coatings with high spatial resolution by using a hyperspectral imaging system. Reflectance spectra were converted to color coordinates revealing characteristic color maps in the color space. Principal-component analysis was applied to decorrelate the spatial variability of the reflectance spectra. We found that the eigenvalue spectra follow different power laws. The scaling exponent was analyzed by considering random-walk-type processes. An estimation of the Hurst exponent was done, suggesting anomalous diffusion from multiple light scattering. The results show that hyperspectral imaging combined with principal-component analysis provides a valuable method for nondestructive testing of complex turbid media. PMID- 22086048 TI - Enhancement of optical processes in coupled plasmonic nanocavities [Invited]. AB - We present detailed experimental and numerical investigations of resonances in deep nanogroove gratings in metallic substrates. These plasmonic nanocavity gratings feature enhanced fields within the grooves that enable a large enhancement of linear and nonlinear optical processes. This enhancement relies on both localized and propagating surface plasmons on the nanopatterned surface. We show that the efficiency of optical processes such as Raman scattering and four wave mixing is dramatically enhanced by plasmonic nanocavity gratings. PMID- 22086049 TI - Enhanced absorptive characteristics of metal nanoparticle-coated silicon nanowires for solar cell applications. AB - The optical properties of metal nanoparticle (NP)-coated silicon nanowires (Si NWs) are theoretically investigated using COMSOL Multiphysics commercial software. A geometrical array of periodic Si NWs coated with metal NPs is proposed. The simulation demonstrates that light absorption could be enhanced significantly in a long wavelength region of the solar spectrum, based upon the localized surface plasmons generated around metal NPs. Various metal NPs, such as Au, Ag, and Al, are all found to increase their light absorption while in contact with Si NWs, in which the Au NPs show the best result in light enhancement. This theoretical work might prove useful in providing a fundamental understanding toward improving further the efficiency of Si wired solar cells. PMID- 22086050 TI - Preparation of wide range refractive index diamond-like carbon films by means of plasma-enhanced chemical vapor deposition. AB - Plasma-enhanced chemical vapor deposition technology has been elaborated for obtaining diamond-like carbon (DLC) coatings of a wide range of properties. Alternative and direct bias voltages have been applied on the substrate, and refractive index dependencies upon various deposition technological parameters have been investigated. The frequency of the bias voltage has been varied in the region of 150-450 kHz. The maximum refractive index range that has been achieved is 1.46-3.2. Thin DLC films have been prepared on crystalline silicon substrates. Because of the wide range of physical, optical, and mechanical properties of the obtained films, they can successfully be applied in different fields of nano optics. PMID- 22086051 TI - Polymer microfiber rings for high-sensitivity optical humidity sensing. AB - We demonstrate microrings assembled with polyacrylamide (PAM) microfibers for high-sensitivity relative humidity (RH) sensing. When exposed to moisture, the PAM microfiber absorbs water molecules and inflates monotonically with the increasing humidity, resulting in evident spectral shifts of the resonance peaks of the microring. By measuring the spectral shifts, the microring shows sensitivity as high as 490 pm/%RH and a response time of about 120 ms, within a dynamic range from 5% to 71% RH. PMID- 22086052 TI - Tuning of localized surface plasmon resonance of well-ordered Ag/Au bimetallic nanodot arrays by laser interference lithography and thermal annealing. AB - A novel hybrid approach to fabricate large-area well-ordered Ag/Au bimetallic nanodot arrays and its potential applications for biosensing is investigated. With the combination of laser interference lithography and the thermal annealing technique, Ag/Au bimetallic nanodots about ~50 nm are formed inside periodic nanodisk arrays at a dimension of ~530 nm on quartz substrates. Extinction spectra of the fabricated nanostructures show their localized surface plasmon resonance (LSPR) can be well controlled by Au concentration, which offers a means to flexibly tune the optical properties of the nanodot arrays. To study the sensitivity of the nanodot arrays, resonance wavelength changes per refractive index unit (RIU) are performed in different surrounding environments. This shows a 94% increase in peak shift per refractive index unit (nanometers/RIU) compared to the nanodot arrays formed only by thermal annealing. These results demonstrate a feasible approach to improve LSPR-based biosensor performance. PMID- 22086053 TI - Theoretical and experimental studies on tightly focused vector vortex beams. AB - The high-NA focusing properties of vector vortex beams are studied theoretically and experimentally. The vector vortex beams are generated by space-variant segmented subwavelength metallic gratings first. Then the mathematical expressions for the focused fields are derived based on the vector diffraction theory, and some numerical simulations are presented that show that the focused fields are not dark at the center and the focusing spot size of vector vortex beams with high topological charges approaches the diffraction limitation at high NA. Finally, to verify the theoretical analysis, the tightly focused fields are measured based on a confocal microscopy system when the NA of the objective lens is 0.90. The research results confirm the potential of vector vortex beams in some applications, such as optical trapping, laser printing, lithography, and material processing. PMID- 22086054 TI - Two-dimensional subwavelength imaging from a hemispherical hyperlens. AB - We report a hemispherical-shaped hyperlens with subwavelength resolution less than 100 nm. Simulations with the finite-element method show that with a 365 nm illumination, the hemispherical hyperlens isotropically magnifies the image along the radial direction. Under linearly polarized light, portions of an object can be resolved. A complete image of the object can be generated by superposing sufficient number of images obtained with incident light in different polarization directions. Such a hyperlens has great potential for realization of nanoscale imaging. PMID- 22086055 TI - Disorder effect in the transmission spectra of a noncompact single layer of dielectric spheres derived from microwave spectroscopy. AB - Single layers of dielectric spheres are an interesting system to study from the fundamental and applied points of view. In this paper we present a systematic study of the influence of structural disorder on the transmission spectra of arrangements of spheres of different compactness. Glass sphere (epsilon=7) planes were built and their transmission spectra in the microwave range measured. Transmission behavior of this system is highly tolerant to disorder. Even in completely disordered arrangements, there is a highly rejected band with the dips of the spectrum observable. These results suggest that the collective modes of the sphere planes are formed by weakly coupled Mie modes of the individual spheres, and this coupling is governed by the average distance among the spheres. Disorder tolerance allows simpler fabrication procedures where the position of the spheres does not need to be precisely controlled. PMID- 22086056 TI - Wideband slow light with ultralow dispersion in a W1 photonic crystal waveguide. AB - A dispersion tailoring scheme for obtaining slow light in a silicon-on-insulator W1-type photonic crystal waveguide, novel to our knowledge, is proposed in this paper. It is shown that, by simply shifting the first two rows of air holes adjacent to the waveguide to specific directions, slow light with large group index, wideband, and low group-velocity dispersion can be realized. Defining a criterion of restricting the group-index variation within a +/-0.8% range as a flattened region, we obtain the ultraflat slow light with bandwidths over 5.0, 4.0, 2.5, and 1.0 nm when keeping the group index at 38.0, 48.8, 65.2, and 100.4, respectively. Numerical simulations are performed utilizing the three-dimensional (3D) plane-wave expansion method and the 3D finite-difference time-domain method. PMID- 22086057 TI - Applications of Nano-optics. AB - As nanoscale fabrication techniques advance, nano-optics continues to offer enabling solutions to numerous practical applications for information optics. This Applied Optics feature issue focuses on the Application of Nano-optics. PMID- 22086058 TI - Animal models of Rift Valley fever virus infection. AB - Emerging and naturally occurring infectious diseases from bacterial and viral sources are constantly threatening humans and livestock. Recently, a variety of infectious diseases have emerged into previously disease-free areas, resulting in new epidemics. Consequently, governmental agencies and researchers in the area of biomedical research have started designing ways to prevent their further spread. Ongoing research activities are focused on developing therapeutic and prophylactic interventions against these emerging infections. Development and evaluation of vaccines, diagnostics and treatments often depend on the development of appropriate animal models to determine the efficacy of new therapeutic agents. In addition, animal models are necessary to understand the basic pathobiology of infection. In this minireview, the current animal models used for one of these emerging infectious diseases, Rift Valley fever virus (RVFV), and the specifics of infection and pathology associated with each model are discussed. PMID- 22086059 TI - Evidence of extended alternate coreceptor usage by HIV-1 clade C envelope obtained from an Indian patient. AB - HIV-1 clade C tends to exclusively use CCR5 irrespective of disease stages. We previously reported envelopes (Envs) obtained from an Indian patient (VB105) that used CXCR4, CXCR6, CCR2b, CCR3, GPR15, and CX3CR1 as additional coreceptors besides CCR5 for entry. Here we show that the primary VB105 virus was able to replicate in peripheral blood mononuclear cells (PBMCs) in presence of inhibitors that antagonizes all the above seven coreceptors at excess doses. In addition, VB105 Envs were found to efficiently infect CCR5-defective T cells (MOLT-4) in presence of excess TAK-779, AMD3100, vMIP-1 and vMIP-2 further substantiated the usage of additional coreceptors beyond the seven coreceptors as reported earlier by VB105 Env. Interestingly, VB105 Envs showed spontaneous exposure of CD4 induced epitopes and found to be associated with increased infection of macrophages. Information on HIV-1 clade C using alternate coreceptors in primary cells to better understand their impact on pathogenesis and efficacy to future entry inhibitors. PMID- 22086060 TI - [Outpatient surgery. Quo vadis?]. PMID- 22086062 TI - From karyotyping to array-CGH in prenatal diagnosis. AB - Conventional karyotyping detects chromosomal anomalies in up to 35% of pregnancies with fetal ultrasound anomalies, depending on the number and type of these anomalies. Extensive experience gained in the past decades has shown that prenatal karyotyping is a robust technique which can detect the majority of germline chromosomal anomalies. For most of these anomalies the phenotype is known. In postnatal diagnosis of patients with congenital anomalies and intellectual disability, array-CGH/SNP array has become the first-tier investigation. The higher abnormality detection yield and its amenability to automation renders array-CGH also suitable for prenatal diagnosis. As both findings of unclear significance and unexpected findings may be detected, studies on the outcome of array-CGH in prenatal diagnosis were initially performed retrospectively. Recently, prospective application of array-CGH in pregnancies with ultrasound anomalies, and to a lesser extent in pregnancies referred for other reasons, was studied. Array-CGH showed an increased diagnostic yield compared to karyotyping, varying from 1-5%, depending on the reason for referral. Knowledge of the spectrum of array-CGH anomalies detected in the prenatal setting will increase rapidly in the years to come, thus facilitating pre- and posttest counseling. Meanwhile, new techniques like non-invasive prenatal diagnosis are emerging and will claim their place. In this review, we summarize the outcome of studies on prenatal array-CGH, the clinical relevance of differences in detection rate and range as compared to standard karyotyping, and reflect on the future integration of new molecular techniques in the workflow of prenatal diagnosis. PMID- 22086063 TI - On the interpretation of IETS spectra of a small organic molecule. AB - We have investigated vibrational spectra of nitrobenzene molecules adsorbed on Cu(111) by low temperature inelastic electron tunneling spectroscopy. This molecule, which should support 39 internal modes, only gives rise to seven peaks in the spectra. We outline a comparison with ensemble IR data and interpret the small number of vibrational peaks by the superposition of a multitude of almost isoenergetic vibrational modes. The non-detectability of further modes cannot be understood in terms of symmetry considerations. Additional modes in the spectra are attributed to external molecular-metal vibrations. PMID- 22086061 TI - Tumor-specific retargeting of an oncogenic transcription factor chimera results in dysregulation of chromatin and transcription. AB - Chromosomal translocations involving transcription factor genes have been identified in an increasingly wide range of cancers. Some translocations can create a protein "chimera" that is composed of parts from different proteins. How such chimeras cause cancer, and why they cause cancer in some cell types but not others, is not understood. One such chimera is EWS-FLI, the most frequently occurring translocation in Ewing Sarcoma, a malignant bone and soft tissue tumor of children and young adults. Using EWS-FLI and its parental transcription factor, FLI1, we created a unique experimental system to address questions regarding the genomic mechanisms by which chimeric transcription factors cause cancer. We found that in tumor cells, EWS-FLI targets regions of the genome distinct from FLI1, despite identical DNA-binding domains. In primary endothelial cells, however, EWS-FLI and FLI1 demonstrate similar targeting. To understand this mistargeting, we examined chromatin organization. Regions targeted by EWS FLI are normally repressed and nucleosomal in primary endothelial cells. In tumor cells, however, bound regions are nucleosome depleted and harbor the chromatin signature of enhancers. We next demonstrated that through chimerism, EWS-FLI acquired the ability to alter chromatin. Expression of EWS-FLI results in nucleosome depletion at targeted sites, whereas silencing of EWS-FLI in tumor cells restored nucleosome occupancy. Thus, the EWS-FLI chimera acquired chromatin altering activity, leading to mistargeting, chromatin disruption, and ultimately, transcriptional dysregulation. PMID- 22086064 TI - Novel anti-inflammatory effects of repaglinide in rodent models of inflammation. AB - BACKGROUND: Repaglinide is an FDA-approved treatment for type 2 diabetes mellitus. The anti-inflammatory effect of repaglinide in the absence of diabetes has not been reported previously. It is the objective of this set of studies to investigate the potential anti-inflammatory effects of repaglinide. METHOD: The in vivo anti-inflammatory effects of repaglinide were studied in two different models of delay type hyperreactivity (DTH) response induced by sheep red blood cells (sRBC) and 2,5'-dinitrofluorobenzene (DNFB), and in two different rodent models of lipopolysaccharide (LPS) challenge. RESULTS: In mice systemically sensitized with sRBC, which subsequently received a local injection of sRBC in the footpad, local swelling occurred within 24 h after challenge. Repaglinide was efficacious in attenuating this response. In an orthogonal DTH model using DNFB as the antigen, the animals received topical sensitization with DNFB on their shaved backs, followed by topical challenge on the left ears. Repaglinide efficaciously downregulated the resulting ear swelling response. In mice challenged systemically or intratracheally with LPS, repaglinide significantly decreased serum tumor necrosis factor alpha level and bronchial alveolar lavage fluid MCP-1 levels, respectively. CONCLUSION: This set of data suggests novel anti-inflammatory effects of repaglinide in nondiabetic animals. However, the high dose required for an efficacious effect would make this application impractical in the clinic. PMID- 22086065 TI - Paraganglioma: not just an extra-adrenal pheochromocytoma. AB - PURPOSE: Pheochromocytoma (PCC) and paraganglioma (PG) are evaluated and treated similarly. This study evaluates the hypothesis that tumor characteristics and outcome of patients with PCC and PG are equivalent. METHODS: Records of patients from a single institution undergoing resection of PCC or PG from 1999 to 2010 were reviewed. Data were collected for demographics, operative records, laboratory and pathologic results, adjuvant and palliative therapy given, recurrence, and length of survival. Descriptive statistics were used to describe differences between patients with benign and malignant PCC and PG. Analysis was performed using the Wilcoxon-Mann-Whitney test with p = 0.05 considered as significant. RESULTS: One hundred fifteen patients were identified (106 PCC and nine PG). Of the tumors, 5.2% were bilateral and 10.4% were malignant. Forty three of the 115 patients underwent genetic testing; 21 out of 37 (56.8%) PCC and five out of six (83.3%) PG had a genetic mutation. Twelve patients (seven PCC and five PG) had malignant tumors. Malignant PG (mPG) exhibited more invasive pathologic characteristics. The median sizes of benign and malignant PCC (mPCC) were 4.0 (0.7-14 cm) and 5.5 cm (3.7-11.2 cm), respectively, p = 0.03. The median sizes of benign and mPG were 4.1 (2.7-5.4 cm) and 5.8 cm (4-6.2 cm), respectively, p = 0.11. Sites of recurrence were similar between the groups. Patients with mPG received chemotherapy more often than those with mPCC. With a median follow-up of 54.7 months (2.0-185.3), two out of five mPG and zero out of seven mPCC had died of the disease. CONCLUSION: Tumor size does not appear to correlate with malignancy in a clinically significant manner. Malignant paraganglioma may be more aggressive than malignant pheochromocytoma and is frequently offered more adjuvant therapy. PCC and PG should be evaluated separately in future analyses of these diseases. PMID- 22086066 TI - High levels of cellular proliferation predict pseudoprogression in glioblastoma patients. AB - Radiochemotherapy (RT) with concomitant followed by monthly temozolomide (TMZ) chemotherapy is the gold standard for the treatment of glioblastoma (GBM) patients. GBM patients can experience transient radiological deterioration after concurrent RT/TMZ that stabilizes or even resolves after additional cycles of adjuvant TMZ, a phenomenon defined as radiological pseudoprogression. The aim of this retrospective study was to identify a reliable marker associated with pseudoprogression processes. Patients with histologically proven newly diagnosed GBM were identified from a retrospective database between 2005 and 2009. Predictive factors for pseudoprogression were analyzed from clinical, radiological and biological data. Of the 130 analyzed patients, 63 underwent RT/TMZ treatment followed by cycles of TMZ and were evaluated for radiological responses every two months by magnetic resonance imaging. Early progression was confirmed in 52% (33/63) of the patients, and, within this group, 21% (7/33) displayed evidence of pseudo-progression. The predictive factors were evidenced in terms of clinical or radiological findings. In GBM patients, the level of cellular proliferation (Ki67 indices) emerged as a statistically significant prognostic marker for distinguishing pseudoprogression from actual progression. Our observation, suggesting that GBM associated with a high level of cellular proliferation may differentiate tumor progression from pseudoprogression, warrants further investigation in a large multi-center prospective study. PMID- 22086067 TI - Translaminar screws of the axis--an alternative technique for rigid screw fixation in upper cervical spine instability. AB - C2 pedicle screws or transarticular atlantoaxial screws are technically demanding and carry an increased risk of vertebral artery injury. In up to 20% of cases, pedicle and transarticular screw placement is not possible due to a high-riding vertebral artery or very small C2 pedicles in addition to other anatomical variations. Translaminar screws have been reported to rigidly capture posterior elements of C2 and therefore appear to be a suitable alternative. We present our first experiences and clinical results with this new method in two neurosurgical spine centers. Twenty-seven adult patients were treated between 2007 and 2010 in two neurosurgical spine departments with C2 translaminar screw fixation for upper cervical spine instability of various origins (e.g., trauma, tumor, dens pseudarthrosis). Eight patients were men and 19 were women. Mean age was 68.9 years. In most cases, translaminar screws were used because of contraindications for pedicle or transarticular screws as a salvage technique. All patients were clinically assessed and had CT scans postoperatively to verify correct screw placement. Follow-up was performed with reexamination on an ambulatory basis. Mean follow-up was 7.6 months for all patients. In 27 patients, 52 translaminar screws were placed. There were no intraoperative complications. Postoperatively, we identified four screw malpositions using a new accuracy grading scale. One screw had to be revised because of violation of the spinal canal >4 mm. None of the patients had additional neurological deficits postoperatively, and all showed stable cervical conditions at follow-up. Two patients died due to causes not associated with the stabilization technique. The fusion rate for patients with C1/C2 fixation is 92.9%. Translaminar screws can be used at least as an additional technique for cases of upper cervical spine instability when pedicle screw placement is contraindicated or not possible. The current data suggest comparable biomechanical stability and fusion rates of translaminar screws to other well-known posterior fixation procedures. In addition, translaminar screw placement is technically less demanding and reduces the risk of vertebral artery injury. PMID- 22086068 TI - RNA-Seq of the xylose-fermenting yeast Scheffersomyces stipitis cultivated in glucose or xylose. AB - Xylose is the second most abundant lignocellulosic component besides glucose, but it cannot be fermented by the widely used ethanol-producing yeast Saccharomyces cerevisiae. The yeast Scheffersomyces stipitis, however, is well known for its high native capacity to ferment xylose. Here, we applied next-generation sequencing technology for RNA (RNA-Seq) to generate two high-resolution transcriptional maps of the S. stipitis genome when this yeast was grown using glucose or xylose as the sole carbon source. RNA-Seq revealed that 5,176 of 5,816 annotated open reading frames had a uniform transcription and that 214 open reading frames were differentially transcribed. Differential expression analysis showed that, compared with other biological processes, carbohydrate metabolism and oxidation-reduction reactions were highly enhanced in yeast grown on xylose. Measurement of metabolic indicators of fermentation showed that, in yeast grown on xylose, the concentrations of cysteine and ornithine were twofold higher and the concentrations of unsaturated fatty acids were also increased. Analysis of metabolic profiles coincided with analysis of certain differentially expressed genes involved in metabolisms of amino acid and fatty acid. In addition, we predicted protein-protein interactions of S. stipitis through integration of gene orthology and gene expression. Further analysis of metabolic and protein-protein interactions networks through integration of transcriptional and metabolic profiles predicted correlations of genes involved in glycolysis, the tricarboxylic acid cycle, gluconeogenesis, sugar uptake, amino acid metabolism, and fatty acid beta-oxidation. Our study reveals potential target genes for xylose fermentation improvement and provides insights into the mechanisms underlying xylose fermentation in S. stipitis. PMID- 22086069 TI - Isolation and characterization of a Klebsiella oxytoca strain for simultaneous azo-dye anaerobic reduction and bio-hydrogen production. AB - A facultative anaerobic bacteria strain GS-4-08, isolated from an anaerobic sequence batch reactor for synthetic dye wastewater treatment, was investigated for azo-dye decolorization. This bacterium was identified as a member of Klebsiella oxytoca based on Gram staining, morphology characterization and 16S rRNA gene analysis. It exhibited a good capacity of simultaneous decolorization and hydrogen production in the presence of electron donor. The hydrogen production was less affected even at a high Methyl Orange (MO) concentration of 0.5 mM, indicating a superior tolerability of this strain to MO. This efficient bio-hydrogen production from electron donor can not only avoid bacterial inhibition due to accumulation of volatile fatty acids during MO decolorization, but also can recover considerable energy from dye wastewater. PMID- 22086070 TI - Conditional confined oscillatory dynamics of Escherichia coli strain K12-MG1655 in chemostat systems. AB - A series of continuous- and sequencing-batch reactor experiments were performed to assess the growth dynamics of Escherichia coli strain K12-MG1655 in chemostat systems. Previous mathematical predictions and early experimental results had shown that confined oscillatory dynamics ensue in bioreactor populations, which relates to "group birth and death" events within the population. New results are reported here that generally verify the predictions of the model and show that confined oscillations occur under different initial conditions, but the characteristics of the oscillatory dynamics vary as a function of the hydraulic retention time (HRT). Bioreactors were operated at HRTs ranging from 2.7 to 35 h and, regardless of initial conditions or the imposition of transient operational instabilities, highly patterned oscillations developed when HRT was between ~3 and 8 h. However, outside of this range, bioreactor populations tended to form biofilms on the reactor walls (although the majority of the cells remained suspended in the bulk solution) and stable oscillations were not seen in the bulk phase. This suggests that alternate operating "states" might exist in chemostat populations with biofilm formation and non-homogenous spatial growth influencing "system" dynamics at very low and high HRTs. Although the model accurately predicts a confined dynamic equilibrium for mid-range HRT operations, experimental data show that model predictions do not extend outside of this range, when an alternate stable-state seems to be attained. PMID- 22086071 TI - Biodegradation of polycyclic aromatic hydrocarbons by a halophilic microbial consortium. AB - In this study we investigated the phenanthrene degradation by a halophilic consortium obtained from a saline soil sample. This consortium, named Qphe, could efficiently utilize phenanthrene in a wide range of NaCl concentrations, from 1% to 17% (w/v). Since none of the purified isolates could degrade phenanthrene, serial dilutions were performed and resulted in a simple polycyclic aromatic hydrocarbon (PAH)-degrading culture named Qphe-SubIV which was shown to contain one culturable Halomonas strain and one unculturable strain belonging to the genus Marinobacter. Qphe-SubIV was shown to grow on phenanthrene at salinities as high as 15% NaCl (w/v) and similarly to Qphe, at the optimal NaCl concentration of 5% (w/v), could degrade more than 90% of the amended phenanthrene in 6 days. The comparison of the substrate range of the two consortiums showed that the simplified culture had lost the ability to degrade chrysene but still could grow on other polyaromatic substrates utilized by Qphe. Metabolite analysis by HPLC and GC-MS showed that 2-hydroxy 1-naphthoic acid and 2-naphthol were among the major metabolites accumulated in the Qphe-SubIV culture media, indicating that an initial dioxygenation step might proceed at C1 and C2 positions. By investigating the growth ability on various substrates along with the detection of catechol dioxygenase gene, it was postulated that the uncultured Marinobacter strain had the central role in phenanthrene degradation and the Halomonas strain played an auxiliary role in the culture by utilizing phenanthrene metabolites whose accumulation in the media could be toxic. PMID- 22086072 TI - Fast crystallization of organic glass formers. AB - An unusually fast crystallization of the organic glass former nifedipine has been observed. The crystallization process, starting from an amorphous film to crystalline material, was investigated by time resolved Raman microspectroscopy. The crystallization rates of the initially crystallizing metastable beta-form are four orders of magnitude higher than those of previous studies. PMID- 22086073 TI - Charge state and adduct reduction in electrospray ionization-mass spectrometry using solvent vapor exposure. AB - The benefits of lowering protein ion charge states in electrospray ionization (ESI) have attracted recent interest. We describe a simple approach to decrease protein charge states by exposure of electrospray droplets to neutral solvent vapor such as acetonitrile. The technique allows detection of weak noncovalent complexes, provides preferred charge states for tandem mass spectrometry (MS/MS) dissociation of protein complexes, and has the added benefit of reducing common adducts, such as alkali metals, without the addition of solution additives or the requirement for a secondary spray. PMID- 22086074 TI - Bioconjugation of InGaP quantum dots for molecular sensing. AB - Fluorescence-based molecular sensing and cellular imaging are commonly carried out with the application of organic dyes. Quantum dots (QDs) are now recognized as better tools because they are brighter, size tunable, and more photostable than dyes. Most of the proposed QD-based biosensing systems involve elements of known toxicity. The present work reports the functionalization of biocompatible InGaP/ZnS core-shell QDs with anti-bovine serum albumin (anti-BSA) to exploit them as fluorescent probes for antigen detection. Successful bioconjugation was characterized with the absorption and emission spectra showing blue shifts of around 40 and 30 nm, respectively. Gel electrophoresis and particle size distribution studies further confirmed the mass increment of QDs after their functionalization with anti-BSA. Surface plasmon resonance spectrometry has been used to study the affinity of QD-(anti-BSA) probes for bovine serum albumin (BSA). Photoluminescence quenching of the developed probe is observed in the presence of BSA. PMID- 22086075 TI - Isoeccentric locations are not equivalent: the extent of the vertical meridian asymmetry. AB - Performance in visual tasks is limited by the low-level mechanisms that sample the visual field. It is well documented that contrast sensitivity and spatial resolution decrease as a function of eccentricity and that those factors impair performance in "higher level" tasks, such as visual search. Performance also varies consistently at isoeccentric locations in the visual field. Specifically, at a fixed eccentricity, performance is better along the horizontal meridian than the vertical meridian, and along the lower than the upper vertical meridian. Whether these asymmetries in visual performance fields are confined to the vertical meridian or extend across the whole upper versus lower visual hemifield has been a matter of debate. Here, we measure the extent of the upper versus lower asymmetry. Results reveal that this asymmetry is most pronounced at the vertical meridian and that it decreases gradually as the angular distance (polar angle) from the vertical meridian increases, with eccentricity held constant. Beyond 30 degrees of polar angle from the vertical meridian, the upper to lower asymmetry is no longer reliable. Thus, the vertical meridian is uniquely asymmetric and uniquely insensitive. This pattern of results is consistent with early anatomical properties of the visual system and reflects constraints that are critical to our understanding of visual information processing. PMID- 22086076 TI - Chromosomal evolution in Rodentia. AB - Rodentia is the most species-rich mammalian order and includes several important laboratory model species. The amount of new information on karyotypic and phylogenetic relations within and among rodent taxa is rapidly increasing, but a synthesis of these data is currently lacking. Here, we have integrated information drawn from conventional banding studies, recent comparative painting investigations and molecular phylogenetic reconstructions of different rodent taxa. This permitted a revision of several ancestral karyotypic reconstructions, and a more accurate depiction of rodent chromosomal evolution. PMID- 22086077 TI - The origin and evolution of vertebrate sex chromosomes and dosage compensation. AB - In mammals, birds, snakes and many lizards and fish, sex is determined genetically (either male XY heterogamy or female ZW heterogamy), whereas in alligators, and in many reptiles and turtles, the temperature at which eggs are incubated determines sex. Evidently, different sex-determining systems (and sex chromosome pairs) have evolved independently in different vertebrate lineages. Homology shared by Xs and Ys (and Zs and Ws) within species demonstrates that differentiated sex chromosomes were once homologous, and that the sex-specific non-recombining Y (or W) was progressively degraded. Consequently, genes are left in single copy in the heterogametic sex, which results in an imbalance of the dosage of genes on the sex chromosomes between the sexes, and also relative to the autosomes. Dosage compensation has evolved in diverse species to compensate for these dose differences, with the stringency of compensation apparently differing greatly between lineages, perhaps reflecting the concentration of genes on the original autosome pair that required dosage compensation. We discuss the organization and evolution of amniote sex chromosomes, and hypothesize that dosage insensitivity might predispose an autosome to evolving function as a sex chromosome. PMID- 22086078 TI - Chromosomal dynamics of nucleolar organizer regions (NORs) in the house mouse: micro-evolutionary insights. AB - Variation in the number and chromosomal location of nucleolar organizer regions (NORs) was studied in the house mouse, Mus musculus (2n=40). From an origin in Western Asia, this species colonized the Middle East, Europe and Asia. This expansion was accompanied by diversification into five subspecies. NOR diversity was revealed by fluorescence in situ hybridization using 18S and 28S probes on specimens spanning Asia to Western Europe. The results showed that the house mouse genome possessed a large number of NOR-bearing autosomes and a surprisingly high rate of polymorphism for the presence/absence of rRNA genes on all these chromosomes. All NOR sites were adjacent to the centromere except for two that were telomeric. Subspecific differentiation established from the NOR frequency data was concordant with the overall pattern of radiation proposed from molecular studies, but highlighted several discrepancies that need to be further addressed. NOR diversity in M. musculus consisted of a large number of polymorphic NORs that were common to at least two subspecies, and a smaller number of NORs that were unique to one subspecies. The most parsimonious scenario argues in favor of a subspecific differentiation by lineage sorting of ancestral NOR polymorphisms; only the unique NORs would have appeared by inter-chromosomal transposition, except for the two telomeric ones that may have originated by hybridization with another species. Such a scenario provides an alternative view from the one prevailing in most systematic and phylogenetic analyses that NORs have a high transposition rate due to concerted evolution of rRNA genes. PMID- 22086079 TI - Chromosomal rearrangements and karyotype evolution in carnivores revealed by chromosome painting. AB - Chromosomal evolution in carnivores has been revisited extensively using cross species chromosome painting. Painting probes derived from flow-sorted chromosomes of the domestic dog, which has one of the most rearranged karyotypes in mammals and the highest dipoid number (2n=78) in carnivores, are a powerful tool in detecting both evolutionary intra- and inter-chromosomal rearrangements. However, only a few comparative maps have been established between dog and other non Canidae species. Here, we extended cross-species painting with dog probes to seven more species representing six carnivore families: Eurasian lynx (Lynx lynx), the stone marten (Martes foina), the small Indian civet (Viverricula indica), the Asian palm civet (Paradoxurus hermaphrodites), Javan mongoose (Hepestes javanicas), the raccoon (Procyon lotor) and the giant panda (Ailuropoda melanoleuca). The numbers and positions of intra-chromosomal rearrangements were found to differ among these carnivore species. A comparative map between human and stone marten, and a map among the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), stone marten and human were also established to facilitate outgroup comparison and to integrate comparative maps between stone marten and other carnivores with such maps between human and other species. These comparative maps give further insight into genome evolution and karyotype phylogenetic relationships among carnivores, and will facilitate the transfer of gene mapping data from human, domestic dog and cat to other species. PMID- 22086081 TI - Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra). AB - Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (F(ST) range: 0.06-0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts. PMID- 22086082 TI - Proteomics and bioinformatics analysis of lovastatin-induced differentiation in ARO cells. AB - Lovastatin (lova), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, can induce differentiation in cancer cells at low concentration, thus having potential to be used as an auxiliary agent in cancer therapy. However, biological networks associated with the differentiation effect of lova have not been elucidated. To investigate molecular mechanisms of lova, the present study was aimed at proteomics and bioinformatics analyses on anaplastic thyroid cancer cell line ARO differentiated with low concentration of lova. Thyroid differentiation was induced by treating ARO cells with 25 MUM of lova and confirmed by checking upregulation of some thyroid differentiation markers. Gel-based proteomics analysis was then performed to identify proteins differentially expressed between undifferentiated and lova-differentiated ARO cells. Bioinformatics analysis was finally performed to estimate biological networks regulated by lova. Our results showed that lova impacted on proteins involved in protein folding, biomolecule metabolism, signal transduction, protein expression and protein degradation. Specifically, transfecting ARO cells with plasmid DNA encoding flotillin 1 (FLOT1) up-regulated the thyroid differentiation markers, indicating that FLOT1 might at least partially mediate the lova-induced thyroid differentiation. These data may shed light on the mechanism underlying lova-induced re-differentiation of thyroid cancer, and give a rationale for clinical use of lova as an auxiliary agent in cancer therapy. PMID- 22086080 TI - Characterising chromosome rearrangements: recent technical advances in molecular cytogenetics. AB - Genomic rearrangements can result in losses, amplifications, translocations and inversions of DNA fragments thereby modifying genome architecture, and potentially having clinical consequences. Many genomic disorders caused by structural variation have initially been uncovered by early cytogenetic methods. The last decade has seen significant progression in molecular cytogenetic techniques, allowing rapid and precise detection of structural rearrangements on a whole-genome scale. The high resolution attainable with these recently developed techniques has also uncovered the role of structural variants in normal genetic variation alongside single-nucleotide polymorphisms (SNPs). We describe how array-based comparative genomic hybridisation, SNP arrays, array painting and next-generation sequencing analytical methods (read depth, read pair and split read) allow the extensive characterisation of chromosome rearrangements in human genomes. PMID- 22086083 TI - Serum proteome analysis of vivax malaria: An insight into the disease pathogenesis and host immune response. AB - Vivax malaria is the most widely distributed human malaria resulting in 80-300 million clinical cases every year. It causes severe infection and mortality but is generally regarded as a benign disease and has not been investigated in detail. The present study aimed to perform human serum proteome analysis in a malaria endemic area in India to identify potential serum biomarkers for vivax malaria and understand host response. The proteomic analysis was performed on 16 age and gender matched subjects (vivax patients and control) in duplicate. Protein extraction protocols were optimized for large coverage of the serum proteome and to obtain high-resolution data. Identification of 67 differentially expressed and statistically significant (Student's t-test; p<0.05) protein spots was established by MALDI-TOF/TOF mass spectrometry. Many of the identified proteins such as apolipoprotein A and E, serum amyloid A and P, haptoglobin, ceruloplasmin, and hemopexin are interesting from a diagnostic point of view and could further be studied as potential serum biomarkers. The differentially expressed serum proteins in vivax malaria identified in this study were subjected to functional pathway analysis using multiple software, including Ingenuity Pathway Analysis (IPA), Protein ANalysis THrough Evolutionary Relationships (PANTHER) and Database for Annotation, Visualization and Integrated Discovery (DAVID) functional annotation tool for better understanding of the biological context of the identified proteins, their involvement in various physiological pathways and association with disease pathogenesis. Functional pathway analysis of the differentially expressed proteins suggested the modulation of multiple vital physiological pathways, including acute phase response signaling, complement and coagulation cascades, hemostasis and vitamin D metabolism pathway due to this parasitic infection. This article is part of a Special Issue entitled: Proteomics: The clinical link. PMID- 22086084 TI - Selective intraarterial injection of ICG for fluorescence angiography as a guide to extirpate perimedullary arteriovenous fistulas. AB - BACKGROUND: Fluorescence angiography with indocyanine green (ICG) provides real time information regarding the patency of vessels. To enhance the capability to delineate flow direction, flow velocity and sequence of dye filling in different components of complex spinal vascular lesions such as perimedullary arteriovenous fistulas (AVFs), we tried selective intraarterial injection of ICG with catheterization in the proximity of the AVFs. METHOD: Prior to taking the position for surgery, a metallic introducer sheath was placed into the femoral artery, and placed over the patient's lateral buttock. After the exposure of the AVFs, a standard angiographic catheter was advanced into the proximal portion of the feeding artery and a small volume of diluted ICG (0.06 mg in 5 ml saline for one examination) injected repeatedly. To avoid the thromboembolism, heparinized saline was perfused continuously thorough the catheter and sheath. FINDINGS: The small injection volume and the close proximity of the injection site to the lesions resulted in quick rise and fall of the fluorescence without any background. Time and spatial resolution of analysis were enhanced; flow dynamics such as direction, velocity and alteration after temporary occlusion were well visualized. The feeders and drainers were clearly distinguished, and the shunts could be precisely identified. CONCLUSIONS: Selective intraarterial injection ICG fluorescence angiography was very useful for perimedullary AVFs. Albeit that it requires intraoperative selective catheterization, this repeatable technique has an advantage to improve temporary resolution and provides accurate information of the flow dynamics through the complex anatomy of vascular lesions. PMID- 22086085 TI - Temporal resolution for calling song signals by female crickets, Gryllus bimaculatus. AB - A behavioural gap detection paradigm was used to determine the temporal resolution for song patterns by female crickets, Gryllus bimaculatus. For stimuli with a modulation depth of 100% the critical gap duration was 6-8 ms. A reduction of the modulation depth of gaps to 50% led either to an increase or a decrease of the critical gap duration. In the latter case, the critical gap duration dropped to 3-4 ms indicating a higher sensitivity of auditory processing. The response curve for variation of pulse period was not limited by temporal resolution. However, the reduced response to stimuli with a high duty cycle, and thus short pause durations, was in accordance with the limits of temporal resolution. The critical duration of masking pulses inserted into pauses was 4-6 ms. An analysis of the songs of males revealed that gaps (5.8 ms) and masking pulses (6.9 ms) were at detectable time scales for the auditory pathway of female crickets. However, most of the observed temporal variation of song patterns was tolerated by females. Critical cues such as pulse period and pulse duty cycle provided little basis for inter-individual selection by females. PMID- 22086086 TI - Controlled synthesis and size-dependent thermal conductivity of Fe3O4 magnetic nanofluids. AB - The effect of nanoparticle size (4~44 nm) on the thermal conductivities of heat transfer oils has been systematically examined using iron oxide nanoparticles. Such Fe(3)O(4) nanoparticles were synthesized by a simple one-pot pyrolysis method. The size (16~44 nm), shape and assembly patterns of monodisperse Fe(3)O(4) nanoparticles were modulated by only controlling the amount of Fe(acac)(3). After the as-prepared Fe(3)O(4) NPs were dispersed in heat transfer oils, the prepared magnetic nanofluids exhibit higher thermal conductivity than heat transfer oils, and the enhanced values increase with a decrease in particle size. In addition, the viscosities of all nanofliuids are remarkably lower than that of the base fluid, which has been found for the first time in the nanofluid field. The promising features offer potential application in thermal energy engineering. PMID- 22086089 TI - Correction. PMID- 22086087 TI - Transcriptomic analysis reveals calcium regulation of specific promoter motifs in Arabidopsis. AB - Increases in intracellular calcium concentration ([Ca(2+)](c)) mediate plant responses to stress by regulating the expression of genes encoding proteins that confer tolerance. Several plant stress genes have previously been shown to be calcium-regulated, and in one case, a specific promoter motif Abscisic Acid Responsive-Element (ABRE) has been found to be regulated by calcium. A comprehensive survey of the Arabidopsis thaliana transcriptome for calcium regulated promoter motifs was performed by measuring the expression of genes in Arabidopsis seedlings responding to three calcium elevations of different characteristics, using full genome microarray analysis. This work revealed a total of 269 genes upregulated by [Ca(2+)](c) in Arabidopsis. Bioinformatic analysis strongly indicated that at least four promoter motifs were [Ca(2+)](c) regulated in planta. We confirmed this finding by expressing in plants chimeric gene constructs controlled exclusively by these cis-elements and by testing the necessity and sufficiency of calcium for their expression. Our data reveal that the C-Repeat/Drought-Responsive Element, Site II, and CAM box (along with the previously identified ABRE) promoter motifs are calcium-regulated. The identification of these promoter elements targeted by the second messenger intracellular calcium has implications for plant signaling in response to a variety of stimuli, including cold, drought, and biotic stress. PMID- 22086088 TI - O-acetylation of Arabidopsis hemicellulose xyloglucan requires AXY4 or AXY4L, proteins with a TBL and DUF231 domain. AB - In an Arabidopsis thaliana forward genetic screen aimed at identifying mutants with altered structures of their hemicellulose xyloglucan (axy mutants) using oligosaccharide mass profiling, two nonallelic mutants (axy4-1 and axy4-2) that have a 20 to 35% reduction in xyloglucan O-acetylation were identified. Mapping of the mutation in axy4-1 identified AXY4, a type II transmembrane protein with a Trichome Birefringence-Like domain and a domain of unknown function (DUF231). Loss of AXY4 transcript results in a complete lack of O-acetyl substituents on xyloglucan in several tissues, except seeds. Seed xyloglucan is instead O acetylated by the paralog AXY4like, as demonstrated by the analysis of the corresponding T-DNA insertional lines. Wall fractionation analysis of axy4 knockout mutants indicated that only a fraction containing xyloglucan is non-O acetylated. Hence, AXY4/AXY4L is required for the O-acetylation of xyloglucan, and we propose that these proteins represent xyloglucan-specific O acetyltransferases, although their donor and acceptor substrates have yet to be identified. An Arabidopsis ecotype, Ty-0, has reduced xyloglucan O-acetylation due to mutations in AXY4, demonstrating that O-acetylation of xyloglucan does not impact the plant's fitness in its natural environment. The relationship of AXY4 with another previously identified group of Arabidopsis proteins involved in general wall O-acetylation, reduced wall acetylation, is discussed. PMID- 22086090 TI - Relationships between glide efficiency and swimmers' size and shape characteristics. AB - Glide efficiency, the ability of a body to minimize deceleration over the glide, can change with variations in the body's size and shape. The purpose of this study was to investigate the relationships between glide efficiency and the size and shape characteristics of swimmers. Eight male and eight female swimmers performed a series of horizontal glides at a depth of 70 cm below the surface. Glide efficiency parameters were calculated for velocities ranging from 1.4 to 1.6 m/s for female swimmers (and at the Reynolds number of 3.5 million) and from 1.6 to 1.8 m/s for male swimmers (and at the Reynolds number of 4.5 million). Several morphological indices were calculated to account for the shape characteristics, with the use of a photogrammetric method. Relationships between the variables of interest were explored with correlations, while repeated measures ANOVA was used to assess within-group differences between different velocities for each gender group. Glide efficiency of swimmers increased when velocity decreased. Some morphological indices and postural angles showed a significant correlation with glide efficiency. The glide coefficient was significantly correlated to the chest to waist taper index for both gender groups. For the male group, the glide coefficient correlated significantly to the fineness ratio of upper body, the chest to hip cross-section. For the female group the glide coefficient had a significant correlation with the waist to hip taper index. The findings suggested that gliding efficiency was more dependent on shape characteristics and appropriate postural angles rather than being dependent on size characteristics. PMID- 22086091 TI - Interlaminar versus transforaminal epidural steroids for the treatment of subacute lumbar radicular pain: a randomized, blinded, prospective outcome study. AB - BACKGROUND: There is uncertainty in the literature over the relative effectiveness of lumbar epidural interlaminar (IL) steroid injection versus transforaminal (TF) steroid injection for lumbar radiculopathy. Most studies to date have been retrospective, or technically focused. OBJECTIVE: To complete a randomized, blinded, prospective outcome study of the short-term benefit for IL versus TF epidural steroids for the treatment of subacute lumbar radicular pain. STUDY DESIGN: Prospective, randomized, blinded, subacute efficacy trial. SETTING: Tertiary care pain management center, major metropolitan city, United States. METHODS: After institutional review board approval, 42 age-matched patients with similar lower back pain and unilateral radicular symptoms were enrolled and randomized in a patient and evaluating physician blinded trial to IL or TF epidural steroids from 2007 through 2009. Prior to intervention and 10-16 days after injection, each participant was evaluated by questionnaire and physical exam by an independent physician. All injections were performed by the same physician. Thirty-eight participants completed the study, 18 in the IL group and 20 in the TF group. Four participants required a repeat injection, and 2 participants crossed over to the alternative injection type (IL to TF). RESULTS: Overall, physical exam, diagnostic testing, disability, activity, depression measures, and opioid pill use were similar between the 2 groups, both pre injection baseline and post-injection improvement. In primary outcomes, the post injection follow-up Numeric Rating Scale (NRS) was more greatly reduced in the TF group. The NRS decreased from 7.0 +/- 1.9 to 3.9 +/- 3.1 (mean values +/- standard deviation) in the IL group and 6.4 +/- 2.1 to 1.7 +/- 1.4 in the TF group. The Oswestry Disability Index was reduced from 37.5 +/- 12.6 to 19.0 +/- 16.7 in the IL group and 38.3 +/- 6.4 to 21.6 +/- 16.8 in the TF group. In secondary outcomes, the depression scale was reduced from 4.39 +/- 3.22 to 2.28 +/- 3.20 in the IL group and 4.10 +/- 1.94 to 1.65 +/- 1.63 in the TF group. Walking tolerance was increased from 8.1 +/- 4.6 blocks to 10.6 +/- 4.4 in the IL group and 8.9 +/- 5.3 blocks to 11.8 +/- 4.2 in the TF group. LIMITATIONS: The study did not examine long-term outcomes. A single experienced interventionalist performed all injections. CONCLUSION: Results suggest that patients may experience greater subjective relief, at least initially, from TF epidural steroid injections over IL. However, more objective, and likely subacute, therapeutic effects are similar. PMID- 22086092 TI - Rates of lead migration and stimulation loss in spinal cord stimulation: a retrospective comparison of laminotomy versus percutaneous implantation. AB - BACKGROUND: Neuromodulation has been used to treat neuropathic pain. Leads have been implanted using laminotomy or percutaneous approaches. Laminotomy implantation has been shown to be superior in terms of lead migration when compared to percutaneous implantation. Lead migration has been reported as high as 68% with the percutaneous approach. Because of this, newer anchors have been developed but not tested in vivo. OBJECTIVES: This study tests the hypothesis that newer anchoring systems have improved lead migration rates for percutaneous leads relative to laminotomy leads to the point of parity. This study also analyzed if factors such as laterality of symptoms, lead type, level of implant and diagnosis affect migration rates. STUDY DESIGN: Neurostimulators implanted in the thoracolumbar spine at Henry Ford Hospital between 2006 and 2008 were reviewed for the following: age, sex, diagnosis, lead type, and implant level. Implants were reviewed for the following: age, sex, diagnosis, lead type, implant level, implant method, symptom laterality, loss of stimulation, radiographic lead migration, and time to loss. Loss of capture and lead migration in the laminotomy and percutaneous groups were compared using Fisher's exact test. Variables within each group included: lead type, level of implantation, location of symptoms, and diagnosis. They were compared using Fisher's exact test. Time to loss of stimulation was compared using the Wilcoxon 2-sample test. SETTING: Pain Clinic, Henry Ford Hospital, Detroit, MI. RESULTS: Laminotomies were performed by a single neurosurgeon and percutaneous implants were performed by a single pain medicine specialist. Percutaneous leads were anchored using Titan (Medtronic Corporation, Minneapolis, MN) anchors. Loss of capture was 24% laminotomy and 23% percutaneous with no significant difference between the 2 groups (P = 0.787). Radiographic evidence of migration was 13.63% percutaneous and 12.67% laminotomy with no significant difference (P = 0.999). The average days to loss of stimulation for the laminotomy versus percutaneous were as follows: 124.82 and 323.6 which were not statistically significant. There was no statistical difference in the days to loss of capture between the groups (P = 0.060). There was no significant difference between unilateral or bilateral symptoms in loss of capture within either group (P = 0.263, P = 0.326). There was not enough data to do comparisons by diagnosis. Comparisons of loss of capture based on electrode type was not significant in either group (P = 0.687, P = 0.371). The effect of the spinal level on the lack of recapture rates was not able to be calculated due to the number of levels. LIMITATIONS: Retrospective study. CONCLUSION: Rates of stimulation loss and radiographic lead migration are similar for both laminotomy and percutaneous implantation. Time to loss of stimulation was not statistically different in either group, although there was a trend toward laminotomy leads migrating earlier. Lead type and laterality of symptoms do not affect lead migration rates. The effect of the level of implant and diagnosis was indeterminate. PMID- 22086093 TI - Use of observational mechanical gateway connector in spinal cord stimulation trials. AB - BACKGROUND: Spinal cord stimulation (SCS) is an established treatment option for chronic pain. Prior to permanent implantation, temporary trials are performed to evaluate the SCS treatment. Currently there are multiple manufacturers with varying fundamental differences in delivery and resultant paresthesias. However, trials are typically limited to one manufacturer for the patient to evaluate. OBJECTIVE: To evaluate the role of the Observational Mechanical Gateway (OMG) Connector for patients undergoing SCS trials. STUDY DESIGN: Retrospective cohort design study. Patients undergoing SCS trials were offered at the end of the 7 day trial to experience stimulation using the OMG Connector. SETTING: Academic university-based pain management center. METHOD: Participants were trialed using the OMG Connector at the end of the 7 day spinal cord stimulation trial. Data based on participants' preference were collected. RESULTS: The average pain score at baseline was 7.3 on a 10-point scale overall, with improvement during the SCS trial to 2.9 overall; 3.5 in Medtronic (MT); and 2.4 in St. Jude (SJ) SCS trials (P = 0.04). The average pain score with OMG was 2.6 overall; 2.8 in MT; and 2.4 in SJ (P = 0.28). In terms of overall coverage of pain distribution, paresthesia and overall satisfaction, the P values were 0.24, 0.21 and 0.33 respectively. Overall, 12 of 16 participants underwent permanent implantation. One of the 4 failed trials was successfully retrialed with the OMG Connector. LIMITATIONS: Small sample of participants and the duration of the OMG Connector trial. CONCLUSIONS: The OMG Connector offers patients another opportunity to better access the available treatment options during the SCS trial period. PMID- 22086094 TI - Ultrasound-guided interventional release of rotator interval and posteroinferior capsule for adhesive capsulitis of the shoulder using a specially designed needle. AB - BACKGROUND: Adhesive capsulitis is a common but poorly understood disorder of the shoulder. Various treatments have been developed to manage this condition, but the efficacy of these treatments is controversial. We developed an ultrasound guided, minimally invasive interventional technique to manage adhesive capsulitis of the shoulder using a specially designed needle. OBJECTIVE: To describe the methodological approach of our intervention. STUDY DESIGN: Technical report. SETTING: Pain management clinic. METHODS: Thirteen participants with adhesive capsulitis of the shoulder underwent ultrasound-guided interventional release of the rotator interval and posteroinferior capsule using a specially designed curved Round Needle. A convex ultrasound probe was placed along the oblique coronal plane over the supraspinatus muscle and acromion. Under ultrasonographic guidance, the needle was passed through the supraspinatus muscle and superior labrum and reached the rotator interval. It was moved forward and backward until no resistance was felt. After finishing the rotator interval release, the needle was inserted toward the posteroinferior capsule. While the operator released the adhesion in the posteroinferior capsule by moving the needle forward and backward, an assistant gradually abducted the shoulder. When full abduction of the affected shoulder was achieved, the intervention was completed. RESULTS: Following our intervention, significant improvements in pain levels, glenohumeral range of motion, and Quick Disability of the Arm, Shoulder, and Hand scores were attained at follow-up. LIMITATIONS: Technical report only. Efficacy of this technique is beyond the scope of the article. CONCLUSION: Ultrasound-guided interventional release of the rotator interval and posteroinferior capsule appears to have clinical significance in the management of adhesive capsulitis of the shoulder. PMID- 22086095 TI - Kyphoplasty for the treatment of vertebral compression fractures in a cancer patient with neurological deficits and anterior vertebral wall destruction. AB - BACKGROUND: Percutaneous balloon kyphoplasty is an effective, minimally invasive procedure that is used to relieve pain and stabilize spine fractures caused by severe osteoporosis or osteolysis due to tumor metastasis. However, there remains a risk of bone cement leakage during and after kyphoplasty, especially in cases with severe vertebral wall destruction or neurological deficits. OBJECTIVE: This article presents a case in which kyphoplasty was used to manage these complications in a woman with vertebral compression fractures caused by tumor metastasis. STUDY DESIGN: Case report. SETTING: Pain management clinic. METHODS: The patient was a 76-year-old woman who had severe low back pain, lower extremity weakness, and cauda equina syndrome because of vertebral compression fracture and spinal metastasis with epidural involvement. The patient had a large bony defect in the vertebra that the bone filler device could pass freely through the anterior body wall. Nevertheless, kyphoplasty was successfully performed by using our new cement injection technique, which is a slow injection of the highly viscous bone cement, followed by a second injection 10 minutes later to allow the previously injected cement to harden. RESULTS: The procedure significantly alleviated all symptoms. The day after the procedure, in the absence of additional pain medication, the pain had dropped dramatically to a numerical rating scale 3-4, and there was an improvement in motor function that allowed the patient to sit and go to the bathroom by herself. In addition, the voiding sensation had returned, which allowed the patient to defecate and urinate normally. LIMITATIONS: This report describes a single case report. CONCLUSION: Our new cement injection technique may allow balloon kyphoplasty to be safely and effectively performed in cancer patients with pathological vertebral compression fractures, even if there are large defects in the anterior vertebral wall and neurological deficits. PMID- 22086096 TI - An analysis of reasons for failed back surgery syndrome and partial results after different types of surgical lumbar nerve root decompression. AB - BACKGROUND: Despite the evident progress in treating vertebral column degenerative diseases, the rate of a so-called "failed back surgery syndrome" associated with pain and disability remains relatively high. However, this term has an imprecise definition and includes several different morbid conditions following spinal surgery, not all of which directly illustrate the efficacy of the applied technology; furthermore, some of them could even be irrelevant. OBJECTIVE: To evaluate and systematize the reasons for persistent pain syndromes following surgical nerve root decompression. STUDY DESIGN: Prospective, nonrandomized, cohort study of 138 consecutive patients with radicular pain syndromes, associated with nerve root compression caused by lumbar disc herniation, and resistant to conservative therapy for at least one month. The minimal period of follow-up was 18 months. SETTING: Hospital outpatient department, Russian Federation METHODS: Pre-operatively, patients were examined clinically, applying the visual analog scale (VAS), Oswestry Disability Index (ODI), magnetic resonance imaging (MRI), discography and computed tomography (CT). According to the disc herniation morphology and applied type of surgery, all participants were divided into the following groups: for those with disc extrusion or sequester, microdiscectomy was applied (n = 65); for those with disc protrusion, nucleoplasty was applied (n = 46); for those with disc extrusion, nucleoplasty was applied (n = 27). After surgery, participants were examined clinically and the VAS and ODI were applied. All those with permanent or temporary pain syndromes were examined applying MRI imaging, functional roentgenograms, and, to validate the cause of pain syndromes, different types of blocks were applied (facet joint blocks, paravertebral muscular blocks, transforaminal and caudal epidural blocks). RESULTS: Group 1 showed a considerable rate of pain syndromes related to tissue damage during the intervention; the rates of radicular pain caused by epidural scar and myofascial pain were 12.3% and 26.1% respectively. Facet joint pain was found in 23.1% of the cases. Group 2 showed a significant rate of facet joint pain (16.9%) despite the minimally invasive intervention. The specificity of Group 3 was the very high rate of unresolved or recurred nerve root compression (63.0%); in other words, in the majority of cases, the aim of the intervention was not achieved. The results of the applied intervention were considered clinically significant if 50% pain relief on the VAS and a 40% decrease in the ODI were achieved. LIMITATIONS: This study is limited because of the loss of participants to follow-up and because it is nonrandomized; also it could be criticized because the dynamics of numeric scores were not provided. CONCLUSION: The results of our study show that an analysis of the reasons for failures and partial effects of applied interventions for nerve root decompression may help to understand better the efficacy of the interventions and could be helpful in improving surgical strategies, otherwise the validity of the conclusion could be limited because not all sources of residual pain illustrate the applied technology efficacy. In the majority of cases, the cause of the residual or recurrent pain can be identified, and this may open new possibilities to improve the condition of patients presenting with failed back surgery syndrome. PMID- 22086097 TI - Predictors for persistent neuropathic pain--a Delphi survey. AB - BACKGROUND: Chronic neuropathic pain has a major effect on quality of life. In order to prevent neuropathic pain from becoming chronic and improve neuropathic pain care, it is important to identify predictors associated with the persistence of neuropathic pain. OBJECTIVE: To identify potential predictors associated with the persistence of neuropathic pain. STUDY DESIGN: A 2-round Delphi study. SETTING: University Medical Center and Pain Management Research Center. METHODS: A 2-round Delphi study was conducted among 17 experts in the field of neuropathic pain. Selection of the panel was based on the citation index ranking for neuropathic pain-related research and/or membership in the neuropathic pain special interest group of the International Association for the Study of Pain (IASP), complemented with experts with demonstrated field knowledge.Potential predictors were categorized according to the International Classification of Functioning, Disability and Health model. Participants were asked to identify important predictors, suggest new predictors, and grade the importance on a 0-10 scale. For the second round, predictors were considered important if the median score was >= 7 and the interquartile range (IQR) <= 3. RESULTS: In the first round, 20 predictors were selected and 58 were added by the experts (patient characteristics [15], environmental factors [25], functions & structure [4], participation & health related quality of life [14]). In the second round, 12 predictors were considered important (patient characteristics [4; e.g., depression, pain catastrophizing], environmental factors [surgery as treatment for neuropathic pain], functions & structure [6; e.g., allodynia, duration of the complaints], participation & trait anxiety/depression as a part of health related quality of life). Presence of depression and pain catastrophizing were considered the most important predictors for chronic neuropathic pain (median >= 8; IQR <= 2). LIMITATIONS: The study design did not include plenary discussion among the experts. The meaning of the individual topics used in this study could have been subject to interpretation bias. CONCLUSIONS: Overall, psychological factors and factors related to sensory disturbances were considered important predictors for persistence of neuropathic pain. Activity related factors and previously received paramedical and alternative treatment were considered to be less important. The list of possible predictors obtained by this study may serve as a basis for development of a clinical prediction rule for chronic neuropathic pain. PMID- 22086098 TI - Vertebral augmentation and radiation therapy: which should be given first to patients with malignant vertebral compression fractures? PMID- 22086100 TI - Feasibility study of rapid opioid rotation and titration: is it truly feasible or paradoxical? PMID- 22086102 TI - One more beers? It's time to STOPP! PMID- 22086103 TI - Treatment considerations in painful HIV-related neuropathy. AB - BACKGROUND: Human immunodeficiency virus (HIV)-related distal sensory polyneuropathy (DSP) is the most common HIV-associated sensory neuropathy. The envelope glycoprotein of HIV-1, gp 120, appears to contribute to this painful neuropathy. Two standard treatments for HIV infection/HIV-related painful DSP (e.g., antiviral therapy [e.g., nucleoside reverse transcriptase inhibitors (NRTI)] opioids) should each be carefully evaluated prior to being utilized to ameliorate the pain of DSP, since they may actually promote nociception. Nucleoside reverse transcriptase inhibitors require activation in the cell via the addition of 3 phosphate groups (by cellular kinases) to their deoxyribose moiety, to form NRTI triphosphates. Subsequently, these deoxynucleotide analogs compete with natural deoxynucleotides for incorporation into the growing viral DNA chain. The incorporation of NRTIs into the viral DNA chain leads to chain termination; since the nucleoside reverse transcriptase inhibitors lack a 3' hydroxyl group on the deoxyribose moiety (unlike natural deoxynucleotides), so that the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Unfortunately, many conventional agents utilized as pharmacologic therapy for neuropathic pain are not effective for providing satisfactory analgesia in painful HIV-related distal sensory polyneuropathy. Although there is no robust data, there does seem to be information which would support the notion of opioids having increased risk of being particularly pronociceptive when being used to treat painful HIV-related neuropathy. It thus appears conceivable that the use of at least certain opioids in efforts to achieve analgesia in patients with painful HIV-related neuropathy may be less than ideal since at least certain opioid analgesics themselves may potentially contribute to "fueling the fire" of HIV enhanced pain hypersensitivity; at least in part via upregulation of specific chemokine receptors (e.g., CXCR4) which seem to be vitally important in promoting HIV related pain facilitation. The risk benefit ratio of treatment with agents such as NRTIs as well as opioids should be reviewed for specific individual patients, prior to clinicians initiating these agents. OBJECTIVES: To raise awareness of the theoretical potential downside that opioids may possess if they are used for the treatment of painful HIV-related neuropathy. METHODS: A narrative review of selected literature. LIMITATIONS: Hypothetical in nature. CONCLUSIONS: Clinicians should consider all aspects of various therapeutic options, carefully weighing the risk/benefit ratios of each potential treatment before initiating opioids for painful HIV-related neuropathy. PMID- 22086104 TI - [Salt consumption and cardiovascular risk : a plea for salt reduction]. AB - High salt intake over long term is associated with increased incidence of arterial, predominantly systolic, hypertension and increased risk of cardiovascular diseases, e.g., stroke, heart failure, and renal insufficiency. High salt consumption is a vascular risk factor generating aortic stiffness and decreased vascular compliance leading to central blood pressure augmentation, higher cardiac load, and diminished diastolic perfusion. The development of heart failure can be a consequence of this sequelae. Randomized trials show a reduction in blood pressure with lower sodium intake. In long-term clinical trials, a reduction in cardiovascular morbidity and mortality has been demonstrated. Recommendations should emphasize the simultaneous reduction in sodium intake and increase in potassium intake. PMID- 22086105 TI - [Risk reduction in cardiovascular diseases by physical activity]. AB - A sedentary lifestyle or physical inactivity is recognized as an important risk factor for cardiovascular diseases. Regular physical activity improves muscular function, cardiac function, and metabolic syndrome-related disorders. Leisure time physical activity reduces all-cause mortality by 22-34% and cardiovascular mortality by 27-35%. These data have been shown in many prospective cohort studies and published in four large meta-analyses with more than 800,000 participants (evidence IA). The risk reduction is somewhat more pronounced in the elderly and in women (IB). In addition to reduced mortality, physical activity also improves cardiopulmonary function and quality of life (IB). This also holds true for coronary artery disease, cardiac failure, and arterial hypertension with high-grade evidence (IA). Furthermore, evidence has been shown a risk reduction in stroke, development of cognitive dysfunction, and intermittent claudication. Training recommendations for physical activity have reached high-grade evidence (IA). Therefore, regular physical activity is one of the most important components of a healthy lifestyle. All physicians should ask their patients at all clinic and office visits about physical activity and recommend activity for prevention and therapy. PMID- 22086106 TI - [Treatment of autoimmune liver diseases. Autoimmune hepatitis and primary sclerosing cholangitis]. AB - Since the 1950s, autoimmune hepatitis has been recognized as a chronic liver disease that responds to treatment with steroids. Nevertheless, even today 25% of all diagnosed patients still present with liver cirrhosis, which emphasizes the importance of a timely and efficient diagnosis. Steroid-containing immunosuppression is characterized by a high rate of unwanted side effects. For non-cirrhotic patients, the synthetic steroid budesonide, which is characterized by high first-pass metabolism, represents a study-evaluated alternative. In the new guidelines for the management of primary sclerosing cholangitis, the therapeutic role of ursodeoxycholic acid has been modified, with no other effective alternative drugs being available. Management of sclerosing cholangitis is also made more difficult by the high risk of cholangiocarcinoma and colon carcinoma in addition to new differential diagnoses such as secondary sclerosing cholangitis and IgG4-associated cholangitis. IgG4-associated cholangitis can mimic primary sclerosing cholangitis but--in contrast-- can respond to the administration of steroid-containing immunosuppression. PMID- 22086107 TI - Interpretation of array comparative genome hybridization data: a major challenge. AB - The advent and application of high-resolution array-based comparative genome hybridization (array CGH) has led to the detection of large numbers of copy number variants (CNVs) in patients with developmental delay and/or multiple congenital anomalies as well as in healthy individuals. The notion that CNVs are also abundantly present in the normal population challenges the interpretation of the clinical significance of detected CNVs in patients. In this review we will illustrate a general clinical workflow based on our own experience that can be used in routine diagnostics for the interpretation of CNVs. PMID- 22086108 TI - Effect of progesterone as a tocolytic and in maintenance therapy during preterm labor. AB - AIMS: To assess the efficacy of vaginal micronized natural progesterone as a tocolytic and in maintenance therapy during threatened preterm birth. METHODS: Eighty-three women with symptoms of threatened preterm birth were either randomized to study groups receiving tocolytic treatment combined with intravaginal micronized natural progesterone (200 mg daily) or to a control group receiving only tocolysis. RESULTS: Micronized natural progesterone treatment resulted in a prolonged latency period of 32.1 +/- 17.8 versus 21.2 +/- 16.3 days in the control group and heavier birth weights of 2,982.8 +/- 697.8 g versus 2,585.3 +/- 746.6 g. No significant differences were found between the groups in admission to the neonatal intensive care unit, stay at the neonatal intensive care unit, need for a mechanical ventilator, respiratory distress syndrome or neonatal sepsis. CONCLUSION: The treatment of threatened preterm birth with tocolytics combined with intravaginal micronized natural progesterone significantly prolonged pregnancy and increased birth weight. However, an improvement in adverse perinatal outcomes was not observed. PMID- 22086109 TI - Structure of bottle-brush brushes under good solvent conditions: a molecular dynamics study. AB - We report a simulation study for bottle-brush polymers grafted on a rigid backbone. Using a standard coarse-grained bead-spring model extensive molecular dynamics simulations for such macromolecules under good solvent conditions are performed. We consider a broad range of parameters and present numerical results for the monomer density profile, density of the untethered ends of the grafted flexible backbones and the correlation function describing the range that neighboring grafted bottle-brushes are affected by the presence of the others due to the excluded-volume interactions. The end beads of the flexible backbones of the grafted bottle-brushes do not access the region close to the rigid backbone due to the presence of the side chains of the grafted bottle-brush polymers, which stretch the chains further in the radial directions. Although a number of different correlation lengths exist as a result of the complex structure of these macromolecules, their properties can be tuned with high accuracy in good solvents. Moreover, qualitative differences with 'typical' bottle-brushes are discussed. Our results provide a first approach to characterizing such complex macromolecules with a standard bead-spring model. PMID- 22086110 TI - Endogenous hydrogen peroxide is a key factor in the yeast extract-induced activation of biphenyl biosynthesis in cell cultures of Sorbus aucuparia. AB - Biphenyls are unique phytoalexins produced by plants belonging to Pyrinae, a subtribe of the economically important Rosaceae family. The formation of aucuparin, a well-known biphenyl, is induced by yeast extract (YE) in cell cultures of Sorbus aucuparia. However, the molecular mechanism underlying YE induced activation of biphenyl biosynthesis remains unknown. Here we demonstrate that the addition of YE to the cell cultures results in a burst of reactive oxygen species (ROS; H(2)O(2) and O(2) (-)), followed by transcriptional activation of the biphenyl synthase 1 gene (BIS1) encoding the key enzyme of the biphenyl biosynthetic pathway and aucuparin accumulation. Pretreatment of the cell cultures with ROS scavenger dihydrolipoic acid and NADPH oxidase-specific inhibitor diphenylene iodonium abolished all of the above YE-induced biological events. However, when the cell cultures was pretreated with superoxide dismutase specific inhibitor N,N-diethyldithiocarbamic acid, although O(2) (-) continued to be generated, the H(2)O(2) accumulation, BIS1 expression and aucuparin production were blocked. Interestingly, exogenous supply of H(2)O(2) in the range of 0.05-10 mM failed to induce aucuparin accumulation. These results indicate that endogenous generation of H(2)O(2) rather than that of O(2) (-) is a key factor in YE-induced accumulation of biphenyl phytoalexins in cell cultures of S. aucuparia. PMID- 22086111 TI - Cockayne syndrome, underlying molecular defects and p53. PMID- 22086112 TI - DNA damage responses in the prostate: implications for cancer formation? PMID- 22086113 TI - Spindle assembly checkpoint and its regulators in meiosis. AB - BACKGROUND Meiosis is a unique form of cell division in which cells divide twice but DNA is duplicated only once. Errors in chromosome segregation during meiosis will result in aneuploidy, followed by loss of the conceptus during pregnancy or birth defects. During mitosis, cells utilize a mechanism called the spindle assembly checkpoint (SAC) to ensure faithful chromosome segregation. A similar mechanism has been uncovered for meiosis in the last decade, especially in the past several years. METHODS For this review, we included data and relevant information obtained through a PubMed database search for all articles published in English from 1991 through 2011 which included the term 'meiosis', 'spindle assembly checkpoint', or 'SAC'. RESULTS There are 91 studies included. Evidence for the existence of SAC functions in meiosis is provided by studies on the SAC proteins mitotic-arrest deficient-1 (Mad1), Mad2, budding uninhibited by benzimidazole-1 (Bub1), Bub3, BubR1 and Mps1; microtubule-kinetochore attachment regulators Ndc80 complex, chromosomal passenger complex, mitotic centromere associated kinesin (MCAK), kinetochore null 1 (KNL1) and Mis12 complex and spindle stability regulators. CONCLUSIONS SAC and its regulators exist and function in meiosis, and their malfunctions may cause germ cell aneuploidy. However, species and sexual differences exist. Moreover, interaction of SAC components with other regulators is still poorly understood, which needs further study. PMID- 22086114 TI - Gold nanoparticles show electroactivity: counting and sorting nanoparticles upon impact with electrodes. AB - Gold nanoparticles (AuNPs) in aqueous 0.10 M HCl are shown to be electroactive at oxidising potentials greater than 1.0 V (vs. Ag/AgCl) by means of voltammetric monitoring of AuNP-electrode collisions. The method promises the use of anodic particle coulometry for the detection and characterisation of the AuNPs. PMID- 22086115 TI - 5-AZA-2'-deoxycytidine induced demethylation influences N-glycosylation of secreted glycoproteins in ovarian cancer. AB - Glycosylation is the most common posttranslational modification of proteins and is highly reflective of changes in the environment of a cell. Epigenetic modifications to the genome are stably transmitted to daughter cells without the requirement for genetic sequence alterations. Aberrant regulation of both epigenetic programming and glycosylation patterning are integral aspects of carcinogenesis. The objective of this study was to determine the interplay between these two complex cellular processes. We demonstrate that global DNA methylation changes in ovarian cancer epithelial cells (OVCAR3) resulted in significant alterations in the glycosylation of secreted glycoproteins. These changes included a reduction in core fucosylation, increased branching and increased sialylation. We further show that the change in core fucose levels was mirrored by altered expression of GMDS and FX, key enzymes in fucose biosynthesis. Alterations in the expression of key glycosyltransferase enzymes such as MGAT5 reflect the changes seen in the branching and sialylation of secreted glycans. Overall, our results highlight that modifications to the epigenetic machinery have a profound effect on the glycan structures generated by cells, which may be a key step in understanding metastasis and drug resistance during cancer progression. PMID- 22086116 TI - Multigenerational programming in the glucocorticoid programmed rat is associated with generation-specific and parent of origin effects. AB - Exposure to an adverse early life environment is associated with increased cardio metabolic disease risk, a phenomenon termed "programming." The effects of this are not limited to the exposed first (F1) generation but can be transmissible to a second generation (F2) through male and female lines. Using a three generation animal model of programming by initial prenatal glucocorticoid overexposure we have identified effects on fetal and placental weight in both the F1 and F2 offspring. However, the expression of candidate imprinted genes in the fetus and placenta differed between the F1 and F2, with marked parent-of-origin effects in F2. Since DNA methylation at imprinted genes is maintained at fertilization, they are potential templates for the transmission of programming effects across generations. Although we detected alterations in DNA methylation at differentially methylated regions (DMRs) of the key prenatal growth factor Igf2 in F1 and F2 fetal liver, the changes in DNA methylation at these DMRs do not appear to underlie the transmission of effects on Igf2 expression through sperm. Thus, multigenerational programming effects on birth weight and disease risk is associated with different processes in F1 and F2. These findings have implications for the pathogenesis and future attempts to stratify therapies for the "developmental component" of cardiometabolic disease. PMID- 22086119 TI - Intrasomatic injection of corticosteroid followed by vertebroplasty increases early pain relief rather than vertebroplasty alone in vertebral bone neoplasms: preliminary experience. AB - PURPOSE: In this prospective multicenter study, we evaluate the effectiveness of corticosteroid plus vertebroplasty rather than vertebroplasty alone in the analgesic treatment of single-level vertebral neoplasms or pathological fractures. MATERIALS AND METHODS: From January 2009 to February 2011, we prospectively enrolled 20 consecutive patients (11 women, nine men; age range 46 78 years; mean age 65.1 years) with single-level vertebral neoplasm or pathological fractures totally or partially refractory to analgesic treatment, with indication to vertebroplasty. Institutional review board approval and informed consent were obtained. The inclusion criteria for the study were the presence of a single-level pathological fracture not extended to the posterior wall or symptomatic localization of primary or secondary neoplasms, visual analogue score (VAS) >=5, and life expectancy more than 3 months. Exclusion criteria where all contraindications either to corticosteroid injection included allergy (local sepsis, bacteremia, allergy) or vertebroplasty included coagulopathy, etc. The population was randomly divided into two groups: in group A, patients underwent intrasomatic injections of 4 mg/ml of dexamethasone phosphate followed by a cement injection; patients in group B underwent standard vertebroplasty. VAS score was evaluated and compared between both groups of patients at 6 h, 24 h, 48 h, 7 days, 30 days, and 3 months after the intervention plus last available follow-up. Statistical analyses were performed by application of the t test. RESULTS: Technical success was achieved in all cases. In group A, we treated six male and six female patients (age range 46-73 years, average 60.2 years). Pre-intervention VAS in group A ranged between 7 and 10 points, average 8 points. In group B, we treated three male and five female patients (age range 52 78 years, average 67.3 years). Pre-intervention VAS score in group B ranged between 7 and 9 points, with an average 8 points. Patients in group A in respect to patients in group B had a higher reduction in VAS, with a difference of 25.4% (VAS reduction average 5.5 versus 4.1) at 6 h post-intervention, 24.5% (VAS average 5.7 versus 4.3) at 24 h, 25% (VAS average 6 versus 4.5) at 48 h, 23% (VAS average 6.5 versus 5) at 7 days, 16.4% (VAS average 6.7 versus 5.6) at 30 days, 8.9% (VAS average 6.7 versus 6, .1) at 3 months. The last available follow-up ranged from 3 to 24 months in group A and from 5 to 20 months in group B. CONCLUSIONS: In our preliminary experience, pre-vertebroplasty injection of intrasomatic corticosteroid in comparison to vertebroplasty alone is able to increase the early pain relief of the procedure. PMID- 22086120 TI - Intramolecular cross-linking in the native JHBP molecule. AB - Juvenile hormone binding protein (JHBP) acts as a shuttle, carrying one of the most crucial hormones for insect development to target tissues. We have found that although the JHBP molecule does not contain tryptophan residues, it exhibits a weak fluorescence maximum near 420nm upon excitation at 315nm. Gel filtration experiments performed in denaturing conditions and ESI-MS analyses excluded the possibility that some low molecular ligand was bound to the protein molecules. Further UV and CD spectroscopy studies, as well as immunoblotting, showed that the unusual JHBP optical properties were due to dityrosine intramolecular cross linking. These bridges were detected both in native and recombinant protein molecules. We believe that in Galleria mellonella hemolymph the DT generation occurs via ROS-mediated oxidation leading to the formation of cross-linked JHBP monomers. MS analyses of peptides generated after JHBP proteolysis indicated, that the dityrosine bridge occurs between the Y128 and Y130 residues. PMID- 22086121 TI - Results of surgery for perforated gastroduodenal ulcers in a Dutch population. AB - OBJECTIVE: Despite improvements in anesthesiology and intensive care medicine, mortality for perforated gastroduodenal ulcer disease remains high. This study was designed to evaluate the results of surgery for perforated ulcer disease and to identify prognostic factors for mortality in order to optimize treatment. PATIENTS AND METHODS: The medical records of 272 patients undergoing emergency surgery for perforated ulcer disease from 2000 to 2005 in two large teaching hospitals and one university hospital in the Netherlands were retrospectively analyzed. Information on 89 pre-, peri- and postoperative data were recorded. Statistical analysis was performed using multiple logistic regression analysis. The primary endpoint was 30-day mortality. RESULTS: The 30-day mortality rate was 16%. Variables associated with 30-day mortality were age, shock, tachycardia, anemia and ASA class. CONCLUSIONS: A relatively low 30-day mortality rate was achieved. Age, shock, tachycardia and anemia were significantly associated with 30-day mortality. Finding that shock, tachycardia and anemia are independently associated with 30-day mortality could indicate that patients are septic upon admission. Improvements in survival might be achieved by early sepsis treatment. PMID- 22086122 TI - Kinetic and kinematic compensations in amputee vertical jumping. AB - A unilateral transtibial amputation causes a disruption to the musculoskeletal system, which results in asymmetrical biomechanics. The current study aimed to assess the movement asymmetry and compensations that occur as a consequence of an amputation when performing a countermovement vertical jump. Six unilateral transtibial amputees and 10 able-bodied (AB) participants completed 10 maximal vertical jumps, and the highest jump was analyzed further. Three-dimensional lower limb kinematics and normalized (body mass) kinetic variables were quantified for the intact and prosthetic sides. Symmetry was assessed through the symmetry index (SI) for each individual and statistically using the Mann-Whitney U test between the intact and prosthetic sides for the amputee group. A descriptive analysis between the amputee and AB participants was conducted to explore the mechanisms of amputee jumping. The amputee jump height ranged from 0.09 to 0.24 m. In the countermovement, all ankle variables were asymmetrical (SI > 10%) and statistically different (p < .05) for the amputees. At the knee and hip, there was no statistical difference between the intact and prosthetic sides range of motion, although there was evidence of individual asymmetry. The knees remained more extended compared with the AB participants to prevent collapse. In propulsion, the prosthesis did not contribute to the work done and the ankle variables were asymmetrical (p < .05). The knee and hip variables were not statistically different between the intact and prosthetic sides, although there was evidence of functional asymmetry and the contribution tended to be greater on the intact compared with the prosthetic side. The lack of kinetic involvement of the prosthetic ankle and both knees due to the limitation of the prosthesis and the altered musculoskeletal mechanics of the joints were the reason for the reduced height jumped. PMID- 22086123 TI - A treatment dilemma in adult immunoglobulin A nephropathy: what is the appropriate target, preservation of kidney function or induction of clinical remission? AB - Immunoglobulin (Ig) A nephropathy is the most common type of glomerulonephritis worldwide. Data on its natural history suggest that approximately 40% of patients progress to end-stage renal failure after 20 years. Various therapies such as antiplatelet medication, fish oil, oral prednisolone, intravenous prednisolone, tonsillectomy, and tonsillectomy plus steroid pulse (TSP) have been proposed. Japanese nephrologists face challenging issues regarding this disease, such as the usefulness of the annual urinary screening system (kenshin) and kidney biopsies, the desire of patients and their families for treatment despite insufficient clinical evidence, and the risk of overtreatment with TSP versus the loss of a 'golden period' with late intervention. We review the current literature on tonsillectomy, steroid therapy, and TSP, which was first proposed in Japan, and present some perspectives on the treatment of IgA nephropathy. PMID- 22086124 TI - Biopsy-proven vancomycin-associated interstitial nephritis and acute tubular necrosis. AB - Fewer than ten biopsy-proven case reports exist on vancomycin-associated interstitial nephritis (VAIN) and vancomycin-associated acute tubular necrosis (VAATN). Among these, several are confounded by the use of other potentially offending drugs. We report a case of isolated VAIN/VAATN in a patient on no other potentially nephrotoxic agents other than vancomycin. The patient received intravenous vancomycin for coagulase-negative staphylococcus bacteremia. Her baseline serum creatinine of 0.9 mg/dL increased to 9.6 mg/dL after 1 week of therapy during which vancomycin levels peaked at 141 MUg/mL. Renal biopsy revealed acute interstitial nephritis with lymphocytic and eosinophilic infiltrate and acute tubular necrosis. Upon discontinuation of vancomycin and administration of prednisone complete renal recovery ensued over a period of 4 weeks. PMID- 22086126 TI - A new case of pure partial 7q duplication. AB - We report on an 18-month-old boy conceived by assisted reproduction technology with developmental delay, hypotonia, microcephaly, frontal bossing, a mild convergent squint, malformed ears, and a short neck. Karyotype analysis revealed a de novo 7q21.1q22.3 duplication characterized by array comparative genomic hybridization (array-CGH) as a segment of 18.69 Mb. Duplications of the long arm of chromosome 7 are uncommon. There are 18 reported cases of different 7q segments with a pure duplication with no additional deletion of other chromosomes. As a consequence, duplications of chromosome 7q have been classified in 4 groups on the basis of the involved region. The present case is included in group 3 which involves interstitial duplications of different sizes. In the literature, only one case with an apparently smaller duplication of the same region has been described. Despite this, the phenotype is different. Moreover, the 2 patients share some phenotypic features, such as psychomotor delay, hypotonia, frontal bossing, short neck, and strabismus. However, the absence of physical characterization in most of the reported cases could justify the lacking phenotype-genotype correlation in patients with partial 7q duplication. Further studies using recent molecular approaches such as array-CGH might permit a more clinically useful grouping of 7q duplications. PMID- 22086125 TI - Mathematics and biology: a Kantian view on the history of pattern formation theory. AB - Driesch's statement, made around 1900, that the physics and chemistry of his day were unable to explain self-regulation during embryogenesis was correct and could be extended until the year 1972. The emergence of theories of self-organisation required progress in several areas including chemistry, physics, computing and cybernetics. Two parallel lines of development can be distinguished which both culminated in the early 1970s. Firstly, physicochemical theories of self organisation arose from theoretical (Lotka 1910-1920) and experimental work (Bray 1920; Belousov 1951) on chemical oscillations. However, this research area gained broader acceptance only after thermodynamics was extended to systems far from equilibrium (1922-1967) and the mechanism of the prime example for a chemical oscillator, the Belousov-Zhabotinski reaction, was deciphered in the early 1970s. Secondly, biological theories of self-organisation were rooted in the intellectual environment of artificial intelligence and cybernetics. Turing wrote his The chemical basis of morphogenesis (1952) after working on the construction of one of the first electronic computers. Likewise, Gierer and Meinhardt's theory of local activation and lateral inhibition (1972) was influenced by ideas from cybernetics. The Gierer-Meinhardt theory provided an explanation for the first time of both spontaneous formation of spatial order and of self-regulation that proved to be extremely successful in elucidating a wide range of patterning processes. With the advent of developmental genetics in the 1980s, detailed molecular and functional data became available for complex developmental processes, allowing a new generation of data-driven theoretical approaches. Three examples of such approaches will be discussed. The successes and limitations of mathematical pattern formation theory throughout its history suggest a picture of the organism, which has structural similarity to views of the organic world held by the philosopher Immanuel Kant at the end of the eighteenth century. PMID- 22086128 TI - Novel HBsAg markers tightly correlate with occult HBV infection and strongly affect HBsAg detection. AB - Occult HBV infection (OBI) is a threat for the safety of blood-supply, and has been associated with the onset of HBV-related hepatocellular carcinoma and lymphomagenesis. Nevertheless, genetic markers in HBsAg (particularly in D genotype, the most common in Europe) significantly associated with OBI in vivo are missing. Thus, the goal of this study is to define: (i) prevalence and clinical profile of OBI among blood-donors; (ii) HBsAg-mutations associated with OBI; (iii) their impact on HBsAg-detection. OBI was searched among 422,278 blood donors screened by Nucleic-Acid-Testing. Following Taormina-OBI-definition, 26 (0.006%) OBI-patients were identified. Despite viremia <50IU/ml, HBsAg-sequences were obtained for 25/26 patients (24/25 genotype-D). OBI-associated mutations were identified by comparing OBI-HBsAg with that of 82 chronically-infected (genotype-D) patients as control. Twenty HBsAg-mutations significantly correlated for the first time with OBI. By structural analysis, they localized in the major HBV B-cell-epitope, and in HBsAg-capsid interaction region. 14/24 OBI-patients (58.8%) carried in median 3 such mutations (IQR:2.0-6.0) against 0 in chronically infected patients. By co-variation analysis, correlations were observed for R122P+S167L (phi=0.68, P=0.01), T116N+S143L (phi=0.53, P=0.03), and Y100S+S143L (phi=0.67, p<0.001). Mutants (obtained by site-directed mutagenesis) carrying T116N, T116N+S143L, R122P, R122P+Q101R, or R122P+S167L strongly decreased HBsAg reactivity (54.9+/-22.6S/CO, 31.2+/-12.0S/CO, 6.1+/-2.4S/CO, 3.0+/-1.0S/CO and 3.9+/-1.3S/CO, respectively) compared to wild-type (306.8+/-64.1S/CO). Even more, Y100S and Y100S+S143L supernatants show no detectable-HBsAg (experiments in quadruplicate). In conclusions, unique HBsAg-mutations in genotype-D, different than those described in genotypes B/C (rarely found in western countries), tightly correlate with OBI, and strongly affect HBsAg-detection. By altering HBV antigenicity and/or viral-particle maturation, they may affect full-reliability of universal diagnostic-assays for HBsAg-detection. PMID- 22086127 TI - Erythropoietin promotes the growth of pituitary adenomas by enhancing angiogenesis. AB - rhEPO is frequently used in clinical practice to treat anemia. However, recently rhEPO has been reported to accelerate tumor growth, progression and metastasis. Many pituitary adenoma patients, particularly those with macroprolactinomas, tend to have anemia and may need rhEPO therapy. To date, whether rhEPO has deleterious effects on pituitary adenomas has not been defined. Here we demonstrated for the first time that human pituitary adenomas are EPOR negative tumors and rhEPO accelerated the tumor growth of MMQ pituitary adenoma xenografts via enhancement of angiogenesis in vivo, whereas rhEPO displayed no direct effect on MMQ cells in vitro. Our mechanistic study showed that rhEPO administration increased phosphorylation of JAK2, STAT3 and VEGF expression in human umbilical vein endothelial cells (HUVECs) in vitro and in MMQ cell xenografts in vivo. Furthermore, VEGF inhibitor attenuated rhEPO induced angiogenesis and delayed tumor growth in MMQ pituitary adenoma xenografts in vivo. JAK2 inhibitor AG490 attenuated EPO induced HUVECs proliferation, phosphorylation of JAK2, STAT3 and VEGF upregulation in vitro and inhibited EPO induced vessel formation in Chicken chorioallantoic membrane (CAM) angiogenesis model in vivo. These results suggest that rhEPO administration may promote the growth of pituitary adenomas by enhancing angiogenesis through EPO-JAK2-STAT3-VEGF signaling pathway. rhEPO should be used with caution in anemia patients bearing pituitary adenoma due to its potential deleterious effects. PMID- 22086129 TI - A conserved matrix epitope based DNA vaccine protects mice against influenza A virus challenge. AB - DNA vaccination represents a unique strategy to overcome the limitations of immunization with conventional vaccines which is restricted by the high variability of influenza viruses. We evaluated the protective efficacy of a plasmid DNA (pDNA), encoding an evolutionarily conserved epitope of viral matrix protein, against the influenza A virus infection. It was found that the mice immunized via the intra-muscular route purely elicited cell mediated immune response to the pDNA, with enhanced level of Th1 cytokines viz. IL-12 and IFNgamma production in the stimulated splenocyte supernatant. The cytotoxic T lymphocytes in the spleen of immunized mice significantly lysed the virus infected MDCK cells. A significant decrease in virus replication was also observed in the lungs of immunized mice and 83% of the mice were protected against the lethal challenge of influenza A viruses. These findings suggest that the plasmid DNA expressing a single matrix epitope may serve as a promising vaccine candidate to provide effective immunity in the susceptible (mouse) population. PMID- 22086130 TI - RNA interference inhibits replication of tick-borne encephalitis virus in vitro. AB - Each year, up to 10,000 cases of infections with the flavivirus tick-borne encephalitis (TBE) virus that affect the central nervous system are reported in Europe and Asia. Due to the potentially severe adverse effects of post-exposure prophylaxis with TBE virus hyperimmunoglobulin, TBE can currently only be treated symptomatically. An RNA interference (RNAi) approach to inhibit TBE virus replication was therefore developed. In this study we demonstrate for the first time that small interfering RNAs (siRNAs) targeted at the TBE virus genome reduce the quantity of infectious TBE virus particles, TBE virus genome, and TBE virus protein in vitro by up to 85%. The 50% inhibitory dose (DI(50)) of the shRNA plasmid was only 0.05MUg/ml. As RNAi-based therapeutics for other diseases are already being evaluated in phases II and III clinical trials, it is possible that RNAi could become valuable tool for controlling TBE virus infection. PMID- 22086131 TI - In vivo comparison of the effects of bupivacaine and levobupivacaine on the pregnant rat myometrium using electrohysterogram. AB - BACKGROUND AND AIMS: The effect of local anesthetics on myometrial contractility during labor analgesia is debatable. We aimed to compare the effects of bupivacaine and levobupivacaine on rat uterine contractility in an in vivo setting. METHODS: Electrical activities of 40 pregnant rat uteruses were recorded on electrohysterogram after dividing the rats into bupivacaine and levobupivacaine groups. Uterine contraction frequencies were recorded at each 5 min interval. The first 5-min recording was considered the control, which was immediately followed by intramyometrial administration of either bupivacaine or levobupivacaine. The recordings were continued for 30 min. The changes in frequencies at each time interval of the groups were compared with each other and the control recording. RESULTS: The frequencies from both groups at each interval were lower than the control values, but not different between the groups. The frequencies of the bupivacaine group during the 5-10 min and 10-15 min intervals were lower than the control time interval, but no significant differences were present between the control and the other time intervals. However, no significant differences were found at any time interval for the levobupivacaine group. CONCLUSION: Levobupivacaine led to less muscle relaxation compared to bupivacaine and may be a better option for labor analgesia and anesthesia considering uterine contractility. PMID- 22086132 TI - Survival and control of Escherichia coli O157:H7 in foods, beverages, soil and water. AB - Escherichia coli O157:H7 is a significant human pathogen which has mostly foodborne and waterborne modes of transmission. Although capable of infecting several hosts, the main source of this bacterium is cattle. In humans, it mainly causes hemorrhagic colitis, bloody diarrhea, and hemolytic uremic syndrome. This bacterial pathogen is fairly resistant to various stresses and can survive for significant periods of time in the environment outside of a host. Some of the factors impacting its survival include the indigenous microbial communities, its ability to attach to food contact surfaces and form biofilms, temperature, and dehydration. To address the public health concerns associated with this pathogen, several disinfection and sanitization procedures and technologies have been developed in recent years. Synergies between different procedures have been evaluated as well. This review addresses recent developments regarding the survival and disinfection of E. coli O157:H7. PMID- 22086133 TI - Turnabout is fair play: use of the bacterial Multivalent Adhesion Molecule 7 as an antimicrobial agent. AB - Pathogen attachment to host tissues is one of the initial and most crucial events during the establishment of bacterial infections and thus interference with this step could be an efficient strategy to fight bacterial colonization. Our recent work has identified one of the factors involved in initial binding of host cells by a wide range of Gram-negative pathogens, Multivalent Adhesion Molecule (MAM) 7. Interference with MAM7-mediated attachment, for example by pre-incubation of host cells with recombinant MAM7, significantly delays the onset of hallmarks of infection, such as pathogen-mediated cytotoxicity or the development of other adhesive structures such as actin pedestals. Thus, we are trying to develop tools based on MAM7 that can be used to prevent or diminish certain Gram-negative bacterial infections. Herein, we describe the use of bead-coupled MAM7 as an inhibitor of infection with the clinically relevant pathogen Pseudomonas aeruginosa. PMID- 22086134 TI - A first-principles description of proton-driven spin diffusion. AB - Herein we design a reduced Liouville space for the simulation of proton-driven spin diffusion. Using this approach, the experimentally observed carbon-13 polarisation transfer in a powder sample undergoing magic-angle spinning is quantitatively described, directly from crystal geometry and without any adjustable parameters. PMID- 22086135 TI - Synthesis and structure of the first clathrochelate iron(II) tris-dioximates with inherent nitrile substituent(s) and new dehalogenation--reduction reaction at a quasi-aromatic macrobicyclic framework. AB - Monoribbed-substituted mono- and dicyano-functionalized iron(II) macrobicycles were obtained for the first time by the reaction of iron(II) diiodoclathrochelate precursor with copper(I) cyanide-triphenylphosphine complex under mild conditions. The target dinitrile clathrochelate is a minor product of this reaction, whereas the major product contains only one cyano group. The clathrochelates obtained were characterized using elemental analysis, (1)H and (13)C{(1)H} NMR, IR and UV-vis spectroscopy, MALDI-TOF spectrometry and X-ray diffraction crystallography. The geometry of their FeN(6)-coordination polyhedra is intermediate between a trigonal prism (TP) and a trigonal antiprism (TAP); the distortion angles, phi, are 22.6-24.7 degrees . In the molecule of the precursor, the Fe-N distances are close, whereas in the mononitrile macrobicycles those for their functionalized chelate fragments are substantially smaller than the corresponding distances in the alpha-benzyldioximate moieties. The heights, h, of the TP-TAP coordination polyhedra and the average bite angles, alpha, (2.33 A and 39 degrees , respectively) are the same for the X-rayed clathrochelates. The UV vis spectra indicate a dramatic redistribution of the electron density in the pi conjugated clathrochelate framework caused by functionalization with inherent nitrile substituents. The proposed mechanism of the dehalogenation-reduction reaction of iron(II) diiodoclathrochelate resulting in substitution of their iodine atoms by a cyano group and hydrogen atom includes the anion-radical hydrodehalogenation of this precursor with acetonitrile as a source of hydrogen atom. Then, the monomethinemonoiodine macrobicyclic product underwent a substitution with a cyano group only. The copper(I) cyanide-triphenylphosphine acetonitrile system is proposed as a tool for the synthesis of nitrile derivatives of electron-withdrawing heterocycles starting from their halogen containing precursors. PMID- 22086136 TI - Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women. AB - PURPOSE: Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated. METHODS: We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). RESULTS: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (beta=-0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD. CONCLUSIONS: After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight. PMID- 22086137 TI - High glucose concentrations alter the biomineralization process in human osteoblastic cells. AB - Diabetes mellitus (DM) may alter bone remodeling, as osteopenia and osteoporosis are among the complications. Moreover, DM increases the risk and severity of chronic inflammatory periodontal disease, in which bone resorption occurs. Broad evidence suggests that chronic inflammation can contribute to the development of DM and its complications. Hyperglycemia is a hallmark of DM that may contribute to sustained inflammation by increasing proinflammatory cytokines, which are known to cause insulin resistance, via toll-like receptor (TLR)-4-mediated mechanisms. However, the mechanisms by which bone-related complications develop in DM are still unknown. Studies done on the effect of high glucose concentrations on osteoblast functions are contradictory because some suggest increases (although others suggest reductions) in the biomineralization process. Therefore, we evaluated the effect of high glucose levels on biomineralization and inflammation markers in a human osteoblastic cell line. Cells were treated with either physiological 5.5 mM or increasing concentrations of glucose up to 24 mM, and we determined the following: i) the quantity and quality of calcium deposit crystals in culture and ii) the expression of the following: a) proteins associated with the process of biomineralization, b) the receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG), c) cytokines IL1, IL6, IL8, IL10, MCP-1 and TNF alpha, and d) TLR-2, -3, -4 and -9. Our results show that high glucose concentrations (12 mM and particularly 24 mM) alter the biomineralization process in osteoblastic cells and provoke the following: i) a rise in mineralization, ii) an increase in the mRNA expression of RANKL and a decrease of OPG, iii) an increase in the mRNA expression of osteocalcin, bone sialoprotein and the transcription factor Runx2, iv) a diminished quality of the mineral, and v) an increase in the expression of IL1beta, IL6, IL8, MCP-1 and IL10 mRNAs. In addition we found that both high glucose levels and hyperosmotic conditions provoked TLR-2, -3, -4 and -9 overexpression in osteoblastic cells, suggesting that they are susceptible to osmotic stress. PMID- 22086138 TI - Atrial fibrillation as an uncommon presentation in a large pleomorphic xanthoastrocytoma. PMID- 22086140 TI - Basic cell physiological activities (cell adhesion, chemotaxis and proliferation) induced by selegiline and its derivatives in Mono Mac 6 human monocytes. AB - Selegiline (R-deprenyl), a monoamine oxidase-B (MAO-B) inhibitor, has complex pharmacological effect that contributes to treatment of neurodegenerative diseases such as Parkinson's and presumably Alzheimer's disease and might work as an inhibitor of tumor growth. In respect of tumorigenesis and metastasis formation, the controlled modifications of adhesion and migration have high therapeutic significance. In the present study, our purpose was to investigate cell physiological responses (adhesion, chemotaxis and proliferation) induced by selegiline, its metabolites and synthetic derivatives and to find some correlations between the molecular structure and the reported antitumor behavior of the derivatives. Our results demonstrated that both R- and S-deprenyls have the potency to elicit increased adhesion and a chemorepellent activity in monocyte model (Mono Mac 6 cell line derived from monoblastic leukemia); however, only the R-enantiomer proved to be cytotoxic. Among the metabolites R-amphetamine has retained the adhesion inducer and the chemorepellent effect of the parent drug on the most significant level. In contrast, a reversed chemotactic effect and an improved cytotoxic character were detected in the presence of fluoro group (p-fluoro-S-deprenyl). In summary, the adhesion inducer activity, chemorepellent and advantageous cytotoxic effects of selegiline and some derivatives indicate that these drug molecules might have inhibitory effects in metastasis formation in primary tumors. PMID- 22086139 TI - Recent rodent models for Alzheimer's disease: clinical implications and basic research. AB - Alzheimer's disease (AD) is the most common origin of dementia in the elderly. Although the cause of AD remains unknown, several factors have been identified that appear to play a critical role in the development of this debilitating disorder. In particular, amyloid precursor protein (APP), tau hyperphosphorylation, and the secretase enzymes, have become the focal point of recent research. Over the last two decades, several transgenic and non-transgenic animal models have been developed to elucidate the mechanistic aspects of AD and to validate potential therapeutic targets. Transgenic rodent models over expressing human beta-amyloid precursor protein (beta-APP) and mutant forms of tau have become precious tools to study and understand the pathogenesis of AD at the molecular, cellular and behavioural levels, and to test new therapeutic agents. Nevertheless, none of the transgenic models of AD recapitulate fully all of the pathological features of the disease. Octodon degu, a South American rodent has been recently found to spontaneously develop neuropathological signs of AD in old age. This review aims to address the limitations and clinical relevance of transgenic rodent models in AD, and to highlight the potential for O. degu as a natural model for the study of AD neuropathology. PMID- 22086141 TI - Intermittent hypoxia activates temporally coordinated transcriptional programs in visceral adipose tissue. AB - Obstructive sleep apnea (OSA) is a prevalent disorder characterized by intermittent hypoxia (IH) during sleep. OSA is strongly associated with obesity and dysregulation of metabolism-yet the molecular pathways linking the effects of IH on adipocyte biology remain unknown. We hypothesized that exposure to IH would activate distinct, time-dependent transcriptional programs in visceral adipose tissue of mice. We exposed 36 mice to IH or normoxia for up to 13 days. We transcriptionally profiled visceral fat tissue harvested from the animals and performed functional enrichment and network analysis on differentially expressed genes. We identified over 3,000 genes with significant expression patterns during the time course of IH exposure. The most enriched pathways mapped to metabolic processes, mitochondrion, and oxidative stress responses. We confirmed the pathophysiological relevance of these findings by demonstrating that mice exposed to chronic IH developed dyslipidemia and underwent significant lipid and protein oxidation within their visceral adipose depots. We applied gene-gene interaction network analysis to identify critical controllers of IH-induced transcriptional programs in adipocytes-these network hubs represent putative targets to modulate the effects of chronic IH on adipose tissue. Our approach to integrate computational methods with gene expression profiling of visceral fat tissue during IH exposure shows promise in helping unravel the mechanistic links between OSA and adipocyte biology. PMID- 22086142 TI - Oral colon delivery of insulin with the aid of functional adjuvants. AB - Oral colon delivery is currently considered of importance not only for the treatment of local pathologies, such as primarily inflammatory bowel disease (IBD), but also as a means of accomplishing systemic therapeutic goals. Although the large bowel fails to be ideally suited for absorption processes, it may indeed offer a number of advantages over the small intestine, including a long transit time, lower levels of peptidases and higher responsiveness to permeation enhancers. Accordingly, it has been under extensive investigation as a possible strategy to improve the oral bioavailability of peptide and protein drugs. Because of a strong underlying rationale, most of these studies have focused on insulin. In the present review, the impact of key anatomical and physiological characteristics of the colon on its viability as a protein release site is discussed. Moreover, the main formulation approaches to oral colon targeting are outlined along with the design features and performance of insulin-based devices. PMID- 22086143 TI - Relationship between PSA kinetics and [18F]fluorocholine PET/CT detection rates of recurrence in patients with prostate cancer after total prostatectomy. AB - PURPOSE: The aim of the present study was to identify prostate-specific antigen (PSA) threshold levels, as well as PSA velocity, progression rate and doubling time in relation to the detectability and localization of recurrent lesions with [(18)F]fluorocholine (FC) PET/CT in patients after radical prostatectomy. METHODS: The study group comprised 82 consecutive patients with biochemical relapse after radical prostatectomy. PSA levels measured at the time of imaging were correlated with the FC PET/CT detection rates in the entire group with PSA velocity (in 48 patients), with PSA doubling time (in 47 patients) and with PSA progression (in 29 patients). RESULTS: FC PET/CT detected recurrent lesions in 51 of the 82 patients (62%). The median PSA value was significantly higher in PET positive than in PET-negative patients (4.3 ng/ml vs. 1.0 ng/ml; p < 0.01). The optimal PSA threshold from ROC analysis for the detection of recurrent prostate cancer lesions was 1.74 ng/ml (AUC 0.818, 82% sensitivity, 74% specificity). Significant differences between PET-positive and PET-negative patients were found for median PSA velocity (6.4 vs. 1.1 ng/ml per year; p < 0.01) and PSA progression (5.0 vs. 0.3 ng/ml per year, p < 0.01) with corresponding optimal thresholds of 1.27 ng/ml per year and 1.28 ng/ml per year, respectively. The PSA doubling time suggested a threshold of 3.2 months, but this just failed to reach statistical significance (p = 0.071). CONCLUSION: In a study cohort of patients with biochemical recurrence of prostate cancer after radical prostatectomy there emerged clear PSA thresholds for the presence of FC PET/CT-detectable lesions. PMID- 22086144 TI - Laparoscopic sentinel lymph node (SLN) versus extensive pelvic dissection for clinically localized prostate carcinoma. AB - PURPOSE: Lymph node metastasis is an important prognostic factor in prostate cancer (PC). The aim of this prospective study was to evaluate the accuracy of sentinel lymph node (SLN) biopsy by laparoscopy in staging locoregional patients with clinically localized PC. METHODS: A transrectal ultrasound-guided injection of 0.3 ml/100 MBq (99m)Tc-sulphur rhenium colloid in each prostatic lobe was performed the day before surgery. Detection was performed intraoperatively with a laparoscopic probe (Gamma Sup CLERAD) followed by extensive resection. SLN counts were performed in vivo and confirmed ex vivo. Histological analysis was performed by haematoxylin-phloxine-saffron staining, followed by immunohistochemistry (IHC) if the SLN was free of metastasis. RESULTS: The study included 93 patients with PC at intermediate or high risk of lymph node metastases. The intraoperative detection rate was 93.5% (87/93). Nineteen patients had lymph node metastases, nine only in SLN. The false-negative rate was 10.5% (2/19). The internal iliac region was the primary metastatic site (43.3%). Metastatic sentinel nodes in the common iliac region beyond the ureteral junction were present in 13.3%. Limited or standard lymph node resection would have ignored 73.2 and 56.6% of lymph node metastases, respectively. CONCLUSION: Laparoscopy is suitable for broad identification of SLN metastasis, and targeted resection of these lymph nodes significantly limits the risk of extended surgical resection whilst maintaining the accuracy of the information. PMID- 22086145 TI - A finite element model technique to determine the mechanical response of a lumbar spine segment under complex loads. AB - This study presents a CT-based finite element model of the lumbar spine taking into account all function-related boundary conditions, such as anisotropy of mechanical properties, ligaments, contact elements, mesh size, etc. Through advanced mesh generation and employment of compound elements, the developed model is capable of assessing the mechanical response of the examined spine segment for complex loading conditions, thus providing valuable insight on stress development within the model and allowing the prediction of critical loading scenarios. The model was validated through a comparison of the calculated force-induced inclination/deformation and a correlation of these data to experimental values. The mechanical response of the examined functional spine segment was evaluated, and the effect of the loading scenario determined for both vertebral bodies as well as the connecting intervertebral disc. PMID- 22086146 TI - Dendritic cells and damage-associated molecular patterns: endogenous danger signals linking innate and adaptive immunity. AB - Dendritic cells (DCs) are potent antigen-presenting cells critical in regulating the adaptive immune response. The role of DCs is dichotomous; they may both present antigens and the appropriate stimulatory molecules to initiate an adaptive immune response, or they may induce tolerance and release anti inflammatory signals. The activation of immature DCs, required for the expression of the necessary costimulatory T cell molecules, is dependent on pattern recognition receptors. In addition to the pathogen-derived ligands of pattern recognition receptors, several damage-associated molecular patterns (DAMPs) have recently been shown to interact with DCs and dramatically affect their ultimate function. The complex interplay of DAMPs on DCs is clinically important, with implications for transplantation, tumor immunity, autoimmunity, chronic inflammation and other conditions of sterile inflammation such as ischemia reperfusion injury. In this review, we will focus on the role of DAMPs in DC function. PMID- 22086147 TI - Brain-derived neurotrophic factor modulates auditory function in the hearing cochlea. AB - Neurotrophins prevent spiral ganglion neuron (SGN) degeneration in animal models of ototoxin-induced deafness and may be used in the future to improve the hearing of cochlear implant patients. It is increasingly common for patients with residual hearing to undergo cochlear implantation. However, the effect of neurotrophin treatment on acoustic hearing is not known. In this study, brain derived neurotrophic factor (BDNF) was applied to the round window membrane of adult guinea pigs for 4 weeks using a cannula attached to a mini-osmotic pump. SGN survival was first assessed in ototoxically deafened guinea pigs to establish that the delivery method was effective. Increased survival of SGNs was observed in the basal and middle cochlear turns of deafened guinea pigs treated with BDNF, confirming that delivery to the cochlea was successful. The effects of BDNF treatment in animals with normal hearing were then assessed using distortion product otoacoustic emissions (DPOAEs), pure tone, and click-evoked auditory brainstem responses (ABRs). DPOAE assessment indicated a mild deficit of 5 dB SPL in treated and control groups at 1 and 4 weeks after cannula placement. In contrast, ABR evaluation showed that BDNF lowered thresholds at specific frequencies (8 and 16 kHz) after 1 and 4 weeks posttreatment when compared to the control cohort receiving Ringer's solution. Longer treatment for 4 weeks not only widened the range of frequencies ameliorated from 2 to 32 kHz but also lowered the threshold by at least 28 dB SPL at frequencies >=16 kHz. BDNF treatment for 4 weeks also increased the amplitude of the ABR response when compared to either the control cohort or prior to treatment. We show that BDNF applied to the round window reduces auditory thresholds and could potentially be used clinically to protect residual hearing following cochlear implantation. PMID- 22086148 TI - The effects of idebenone on mitochondrial bioenergetics. AB - We have studied the effects of idebenone on mitochondrial function in cybrids derived from one normal donor (HQB17) and one patient harboring the G3460A/MT-ND1 mutation of Leber's Hereditary Optic Neuropathy (RJ206); and in XTC.UC1 cells bearing a premature stop codon at amino acid 101 of MT-ND1 that hampers complex I assembly. Addition of idebenone to HQB17 cells caused mitochondrial depolarization and NADH depletion, which were inhibited by cyclosporin (Cs) A and decylubiquinone, suggesting an involvement of the permeability transition pore (PTP). On the other hand, addition of dithiothreitol together with idebenone did not cause PTP opening and allowed maintenance of the mitochondrial membrane potential even in the presence of rotenone. Addition of dithiothreitol plus idebenone, or of idebenol, to HQB17, RJ206 and XTC.UC1 cells sustained membrane potential in intact cells and ATP synthesis in permeabilized cells even in the presence of rotenone and malonate, and restored a good level of coupled respiration in complex I-deficient XTC.UC1 cells. These findings demonstrate that idebenol can feed electrons at complex III. If the quinone is maintained in the reduced state, a task that in some cell types appears to be performed by dicoumarol-sensitive NAD(P)H:quinone oxidoreductase 1 [Haefeli et al. (2011) PLoS One 6, e17963], electron transfer to complex III may allow reoxidation of NADH in complex I deficiencies. PMID- 22086149 TI - Coupled electron and proton transfer reactions during the O->E transition in bovine cytochrome c oxidase. AB - A combined DFT/electrostatic approach is employed to study the coupling of proton and electron transfer reactions in cytochrome c oxidase (CcO) and its proton pumping mechanism. The coupling of the chemical proton to the internal electron transfer within the binuclear center is examined for the O->E transition. The novel features of the His291 pumping model are proposed, which involve timely well-synchronized sequence of the proton-coupled electron transfer reactions. The obtained pK(a)s and E(m)s of the key ionizable and redox-active groups at the different stages of the O->E transition are consistent with available experimental data. The PT step from E242 to H291 is examined in detail for various redox states of the hemes and various conformations of E242 side-chain. Redox potential calculations of the successive steps in the reaction cycle during the O->E transition are able to explain a cascade of equilibria between the different intermediate states and electron redistribution between the metal centers during the course of the catalytic activity. All four electrometric phases are discussed in the light of the obtained results, providing a robust support for the His291 model of proton pumping in CcO. PMID- 22086151 TI - Economic burden in a German cohort of patients with multiple sclerosis. AB - AIMS: To estimate costs of multiple sclerosis (MS) in a German cohort according to severity of the disease and clinical symptoms. METHODS: 144 patients were recruited from an MS outpatient clinic. Costs were calculated according to current German health-economic guidelines from the perspective of the social health insurance system. Patients were either interviewed or completed a questionnaire. Cost assessment covered a 3-month period. Health outcomes were: Expanded Disability Status Scale, MS Functional Composite, Functional Assessment of MS, fatigue, depression (Beck Depression Inventory II) and patients' socioeconomic status. Multivariate linear regression identified independent cost predictors. RESULTS: Total quarterly costs per patient were EUR 10,329 (95% CI 9,357-11,390). Direct costs were EUR 5,344 for the social health insurance system and EUR 140 for the patient. Drugs represented the major share of direct costs (and 35% of total costs); indirect costs accounted for 47% of total costs. Univariate and multivariate analyses identified age, disability, fatigue and depression as independent predictors for total, indirect or drug costs. CONCLUSION: MS represents a high economic burden, with direct costs exceeding indirect costs. To reduce costs, research should focus on prevention that slows down progression of MS. Rehabilitation and symptomatic treatment may have merits in decreasing indirect costs. PMID- 22086152 TI - Increased ERK activation and cellular drug accumulation in the enhanced cytotoxicity of folate receptor-targeted liposomal carboplatin. AB - Folate receptor-targeted (FRT) liposomes for carboplatin were developed and evaluated in FR-positive and FR-negative cell lines, KB and A549, respectively, for their cytotoxic effects. Significant enhancement in carboplatin potency and intracellular drug accumulation was observed in KB cells when treated with FRT liposomes, compared to free drug and non-targeted liposomes. No enhancement was observed in the FR-negative A549 cells. The increase in carboplatin potency was hypothesized to be associated with an increase in the formation of DNA-platinum adducts resulted from an increase in cellular accumulation of the drug. Surprisingly, FRT carboplatin liposomes showed significantly lower levels of DNA platinum adducts in comparison to free drug. To elucidate this discrepancy, activation of extracellular signal-regulated protein kinase (ERK) was probed, which has been suggested as an alternative mechanism of carboplatin action. FRT liposomes loaded with carboplatin exhibited the highest level of ERK phosphorylation, and the cytotoxic effect of FRT carboplatin liposomes could be reversed by the MEK/ERK inhibitors, U0126 and PD98059. Importantly, empty FRT liposomes could significantly increase ERK phosphorylation in a concentration dependent manner without causing toxicity to cells. For the first time, increased potency of carboplatin delivered by FRT liposomes was found to be associated with other molecular targets in addition to DNA-platinum adduct formation. Collectively, the current study suggests a novel mechanism by which FRT liposomes could sensitize cancer cells to drug treatment via modulation of ERK-related cell survival signals. PMID- 22086150 TI - Adrenocortical neoplasia: evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants. AB - Adrenocortical carcinoma (ACC) is a rare, heterogeneous malignancy with a poor prognosis. According to WHO classification 2004, ACC variants include oncocytic ACCs, myxoid ACCs and ACCs with sarcomatous areas. Herein, we provide a comprehensive review of these rare subtypes of adrenocortical malignancy and emphasize their clinicopathological features with the aim of elucidating aspects of diagnostic categorization, differential diagnostics and biological behavior. The issue of current terminology, applied to biphasic tumors with pleomorphic, sarcomatous or sarcomatoid elements arising in adrenal cortex, is also discussed. We additionally present emerging evidence concerning the adrenal cortical tumorigenesis and the putative adenoma-carcinoma sequence as well. PMID- 22086153 TI - Measuring satiety with pictures compared to visual analogue scales. An exploratory study. AB - Visual analogue scales (VAS) are a standard tool used to measure subjective appetite. To explore a potentially more intuitive and precise alternative, we developed a method based on pictures and assessed its performance characteristics vs. VAS. The objective was to compare the capacity of the two methods to discriminate appetite ratings between interventions. Both methods were applied within a previously published trial in which 16 healthy adults received standardised meals followed by three different ileal infusions in a balanced crossover design. At regular intervals volunteers indicated how many units of individually pictured food portions (for 10 different items) they would like to eat, and also scored six VAS. Methods were compared over different timeframes and assessed for their sensitivity to intervention effects. Pictures were more sensitive than VAS in differentiating intervention effects; however, further refinement and validation would be needed for pictures to become a standardised and accepted alternative to VAS for this type of research. PMID- 22086154 TI - The role of bipolar transurethral vaporization in the management of benign prostatic hyperplasia. AB - OBJECTIVES: A prospective randomized study was conducted to evaluate the safety and effectiveness of bipolar plasma vaporization with a novel electrode that produces vaporization of the tissue (transurethral vaporization of the prostate, TUVP) immersed in isotonic saline compared to the standard transurethral resection of the prostate (TURP) in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From February 2009 to February 2010, 90 patients with BPH were randomized into two groups, and underwent conventional TURP (group 1) or TUVP (group 2) utilizing bipolar plasma vaporization with an innovative electrode (Olympus Winter & Ibe GmbH, Hamburg, Germany). International Prostate Symptom Scores (IPSS), transrectal ultrasonographic findings, maximal urine flow rates (Qmax), and postvoiding residual urine (PVRU) volumes of all cases were evaluated preoperatively and 1 month, 3 months, and 1 year postoperatively. Preoperative and postoperative serum hemoglobin, hematocrit and sodium concentrations of all patients were measured. All patients included in the study were monitored for 1 year. RESULTS: In patients in group 1 (n = 47; mean age: 64.7 +/- 7.3 years) TURP was performed. The patients in group 2 (n = 43; mean age: 65.4 +/- 8.9 years) underwent bipolar TUVP. Cases in the two study groups matched for demographic characteristics and clinical parameters were assessed. The evaluation of IPSS scores, PVRU, Qmax, and prostatic volumes of the patients 1 month, 3 months, and 1 year postoperatively did not reveal any significant differences between the two groups. In group 2 (TUVP), postoperative catheter indwelling times were significantly shorter, and Na serum concentrations were also markedly lower (p < 0.005). CONCLUSION: We detected similar effectiveness and morbidity rates in both groups. Bipolar TUVP has advantages such as shorter catheter indwelling times and hospital stays, and fewer bleeding episodes without any risk of transurethral resection syndrome. We believe that TUVP might be an alternative to TURP which is currently the 'gold standard' treatment in BPH. PMID- 22086155 TI - Spanish validation of the Spence Children's Anxiety Scale. AB - The purpose of this study was to investigate the factorial structure and psychometric properties of the Spence Children's Anxiety Scale (SCAS) in a sample of 1,708 Spanish children aged between 8 and 12 years. The SCAS was demonstrated to have satisfactory internal consistency with the Spanish sample, and factor analysis confirmed the six-factor original model. Convergent validity was supported by correlations with the State-Trait Anxiety Inventory for Children and the welfare dimension of the Child Health and Illness Profile-Children Edition. Low correlations between the SCAS and the Children's Depression Inventory supported the divergent validity. Analysis suggested that anxiety scores decrease with age, and girls reported higher scores than boys. Overall, the SCAS was shown to have good psychometric properties for use with Spanish children by clinicians and researchers. PMID- 22086156 TI - Electrochemical nickel-induced fluoroalkylation: synthetic, structural and mechanistic study. AB - Electrocatalytic generation of nickel catalysts in low oxidation states by reduction of nickel complexes with various ligands (2,2'-bipyridine, 2,2':6',2'' terpyridine, (S,S)-2,6-bis(4-phenyl-2-oxazolin-2-yl)-pyridine) in the presence of olefinic substrates and fluoroalkyl halides leads to new organic products derived from addition-dimerization processes. Due to the presence of two stereocenters in the dimerization products two diastereomers were characterized by a variety of analytical techniques including multi-dimensional NMR methods and X-ray single crystal diffraction. The formation of dimers was prevented by the inclusion of the hydrogen atom donor tributyltin hydride. The cyclic voltammetry study of selected nickel complexes along with fluoroalkyl halides demonstrated that Ni(I)L is the active form of the catalyst. PMID- 22086157 TI - Detection of torque teno midi virus/small anellovirus (TTMDV/SAV) in chronic cervicitis and cervical tumors in Isfahan, Iran. AB - Torque teno midi virus and small anellovirus (TTMDV/SAV) are members of the genus Gammatorquevirus within the family Anelloviridae. Cervical cancer is the second most prevalent cancer after breast cancer. The aim of this study was to determine the frequency of infection by these viruses in cervicitis and cervical tumors of women from Isfahan, Iran. Formalin-fixed, paraffin-embedded tissue samples from cervical cancers (n = 42) and cervicitis cases (n = 79) were subjected to nested PCR to identify TTMDV/SAV viral sequences. Of the 42 tumor cases, 22, 18 and 2 were diagnosed as adenocarcinoma, cervical intraepithelial neoplasia and squamous cell carcinoma, respectively. In total, 23 (55%) of the tumor samples were positive for TTMDV/SAV. Of the 79 cervicitis cases, 38 (48%) were also positive for TTMDV/SAV. This is the first report of TTMDV/SAV in cervicitis and cervical tumors of women. PMID- 22086158 TI - The complete sequence of tobacco mosaic virus isolate Ohio V reveals a high accumulation of silent mutations in all open reading frames. AB - TMVOhioV was first described 1969 by [1] because it did break resistance of tomato breeding lines containing Tm-1- and Tm-2 resistance genes. It was obtained 1987 from Wetter (Saarbrucken, Germany) and transferred into the DSMZ-Plant Virus Collection (Braunschweig, Germany). A partial sequence of TMVOhioV, the CP gene, has been reported [11] and its comparison with a TMV type isolates (TMVtype), e.g. EMBL: V01409, revealed 50 point mutations in a total of 477 nucleotides (nts) leading to the replacement of only 7 amino acids (aa). In order to investigate the mutations in the non-translated regions and the number of silent mutation in the three other open reading frames (ORF), we sequenced the complete genome of isolate TMVOhioV and compared it to those of other Tobamoviruses. PMID- 22086159 TI - Kidney-targeting Smad7 gene transfer inhibits renal TGF-beta/MAD homologue (SMAD) and nuclear factor kappaB (NF-kappaB) signalling pathways, and improves diabetic nephropathy in mice. AB - AIMS/HYPOTHESIS: The TGF-beta/MAD homologue (SMAD) and nuclear factor kappaB (NF kappaB) signalling pathways have been shown to play a critical role in the development of renal fibrosis and inflammation in diabetic nephropathy. We therefore examined whether targeting these pathways by a kidney-targeting Smad7 gene transfer has therapeutic effects on renal lesions in the db/db mouse model of type 2 diabetes. METHODS: We delivered Smad7 plasmids into the kidney of db/db mice using kidney-targeting, ultrasound-mediated, microbubble-inducible gene transfer. The histopathology, ultrastructural pathology and pathways of TGF beta/SMAD2/3-mediated fibrosis and NF-kappaB-dependent inflammation were evaluated. RESULTS: In this mouse model of type 2 diabetes, Smad7 gene therapy significantly inhibited diabetic kidney injury, compared with mice treated with empty vectors. Symptoms inhibited included: (1) proteinuria and renal function impairment; (2) renal fibrosis such as glomerular sclerosis, tubulo-interstitial collagen matrix abundance and renal inflammation, including Inos (also known as Nos2), Il1b and Mcp1 (also known as Ccl2) upregulation, as well as macrophage infiltration; and (3) podocyte and endothelial cell injury as demonstrated by immunohistochemistry and/or electron microscopy. Further study demonstrated that the improvement of type 2 diabetic kidney injury by overexpression of Smad7 was associated with significantly inhibited local activation of the TGF-beta/SMAD and NF-kappaB signalling pathways in the kidney. CONCLUSIONS/INTERPRETATION: Our results clearly demonstrate that kidney-targeting Smad7 gene transfer may be an effective therapy for type 2 diabetic nephropathy, acting via simultaneous modulation of the TGF-beta/SMAD and NF-kappaB signalling pathways. PMID- 22086160 TI - Sources of inputs to the anterior and posterior aspects of the paraventricular nucleus of the thalamus. AB - The paraventricular nucleus of the thalamus (PVT) is part of a group of midline and intralaminar thalamic nuclei implicated in arousal and attention. Recent research points to anatomical and functional differences between the anterior (aPVT) and posterior PVT (pPVT). The present study re-examines the main sources of brain inputs to the aPVT and pPVT in the rat following iontophoretic injections of the retrograde tracer cholera toxin B (CTb) in the PVT. The location and the number of retrogradely labeled neurons in different regions of the brain were examined to determine which brain areas are likely to exert a strong influence on the aPVT and pPVT. The largest number of labeled neurons was found in layer 6 of the prelimbic, infralimbic and posterior insular cortices following injections in the pPVT. In contrast, the largest number of labeled neurons following injections of CTb in the aPVT was found to be in the hippocampal subiculum and the prelimbic cortex. Other areas of the brain including the reticular nucleus of the thalamus, periaqueductal gray, parabrachial nucleus and dorsomedial nucleus of the hypothalamus were found to contain a more moderate number of neurons following injections of CTb in either the aPVT or pPVT. The results of the present tracing study clearly show that more neurons in the prefrontal cortex and subiculum project to the PVT than neurons from the hypothalamus and brainstem. These results highlight the potential importance of top-down modulation of PVT mechanisms and behavioral functions. PMID- 22086161 TI - Vaccination with dendritic cells loaded with tumor apoptotic bodies (Apo-DC) in patients with chronic lymphocytic leukemia: effects of various adjuvants and definition of immune response criteria. AB - We previously demonstrated that autologous dendritic cells that have endocytosed apoptotic bodies of chronic lymphocytic leukemia (CLL) cells (Apo-DC) can stimulate antileukemic T cell responses in vitro. In this phase I study, we vaccinated 15 asymptomatic CLL patients at five time points with Apo-DC administered intradermally either alone (cohort I), or in combination with subcutaneous granulocyte-macrophage-colony-stimulating-factor (GM-CSF) (cohort II) or with GM-CSF and intravenous low-dose cyclophosphamide (cohort III). Aim of the study was to evaluate the safety and immunogenicity of Apo-DC alone or in combination with GM-CSF and low-dose cyclophosphamide in CLL patients. All patients completed the vaccination schedule without dose-limiting toxicity. No objective clinical responses were seen. Vaccine-induced leukemia-specific immune responses were evaluated by IFN-gamma ELISpot and proliferation assays over a 52 weeks observation period and immune response criteria were defined. According to these criteria, 10/15 patients were defined as immune responders. The frequency of immune-responding patients was higher in cohorts II (3/5) and III (5/5) than in cohort I (2/5). In order to further characterize the induced immune response, estimation of secreted cytokines and CD107-degranulation assay were performed. Clustering of T and CLL cells was observed in CD107-degranulation assay and visualized by confocal microscopy. Additionally, assessment of regulatory T cells (T(regs)) revealed their significantly lower frequencies in immune responders versus non-responders (P < 0.0001). Cyclophosphamide did not reduce T(regs) frequency. In conclusion, vaccination with Apo-DC + GM-CSF and cyclophosphamide was safe and elicited anti-CLL immune responses that correlated inversely with T(regs) levels. Lack of clinical responses highlights the necessity to develop more potent vaccine strategies in B cell malignancies. PMID- 22086162 TI - Are we ready to start studies of Th17 cell manipulation as a therapy for cancer? AB - From a therapeutic perspective, the bourgeoning literature on Th17 cells should allow us to decide whether to rationally pursue the manipulation of Th17 cells in cancer. The purpose of this review is to attempt a synthesis of a number of contradictory conclusions as to the role that these cells are playing in the process of tumourigenesis in order to provide guidance as to whether our current understanding is sufficient to safely pursue Th17-targeted therapy in cancer at this time. Th17 cells are a highly plastic population and the cytokine drivers for Th17 cell generation and skewing will vary between various cancers and importantly between different sites of tumour involvement in any individual patient. The net impact of the pro-angiogenic IL-17 produced not only by Th17 cells but by other cells particularly macrophages and the anti-tumour effects of Th1/Th17 cells will in turn be determined by the complex interplay of diverse chemokines and cytokines in any tumour microenvironment. Th17 cells that fail to home to tumours may be immunosuppressive. The complexity of IL-17 and Th17 dynamics makes easy prediction of the effects of either enhancing or suppressing Th17 cell differentiation in cancer problematic. PMID- 22086164 TI - Digital timing: sampling frequency, anti-aliasing filter and signal interpolation filter dependence on timing resolution. AB - The main focus of our study is to investigate how the performance of digital timing methods is affected by sampling rate, anti-aliasing and signal interpolation filters. We used the Nyquist sampling theorem to address some basic questions such as what will be the minimum sampling frequencies? How accurate will the signal interpolation be? How do we validate the timing measurements? The preferred sampling rate would be as low as possible, considering the high cost and power consumption of high-speed analog-to-digital converters. However, when the sampling rate is too low, due to the aliasing effect, some artifacts are produced in the timing resolution estimations; the shape of the timing profile is distorted and the FWHM values of the profile fluctuate as the source location changes. Anti-aliasing filters are required in this case to avoid the artifacts, but the timing is degraded as a result. When the sampling rate is marginally over the Nyquist rate, a proper signal interpolation is important. A sharp roll-off (higher order) filter is required to separate the baseband signal from its replicates to avoid the aliasing, but in return the computation will be higher. We demonstrated the analysis through a digital timing study using fast LSO scintillation crystals as used in time-of-flight PET scanners. From the study, we observed that there is no significant timing resolution degradation down to 1.3 Ghz sampling frequency, and the computation requirement for the signal interpolation is reasonably low. A so-called sliding test is proposed as a validation tool checking constant timing resolution behavior of a given timing pick-off method regardless of the source location change. Lastly, the performance comparison for several digital timing methods is also shown. PMID- 22086163 TI - Receiving treatment, labor force activity, and work performance among people with psychiatric disorders: results from a population survey. AB - INTRODUCTION: Standard treatments for psychiatric disorders such as schizophrenia, depression and anxiety disorders are generally expected to benefit individuals, employers, and the wider community through improvements in work functioning and productivity. METHODS: We repeated a previous secondary investigation of receiving treatment, labor force activity and self-reported work performance among people with ICD-10 psychiatric disorders, in comparison to people with other types of health conditions. Data were collected by the Australian Bureau of Statistics in 2003 repeating a survey administered in 1998 using representative multistage sampling strategies. The 2003 household probability sample consisted of 36,241 working age individuals. RESULTS: Consistent with the previous secondary investigation based on the 1998 survey administration, receiving treatment was consistently associated with non participation in the labor force, and was negatively associated with work performance. CONCLUSIONS: At a population level, receiving treatment was negatively associated with labor force activity and work performance. The stability of these results in two independent surveys highlights the need to investigate the longitudinal relationships between evidence-based treatments for psychiatric conditions as applied in real-world settings, and labor force participation and work performance outcomes. PMID- 22086165 TI - Accessory cells: no longer just the bridesmaids, now at last the bride. The Nobel Prize in physiology or medicine 2011. PMID- 22086166 TI - Efflux pump genes and antimicrobial resistance of Pseudomonas aeruginosa strains isolated from lower respiratory tract infections acquired in an intensive care unit. AB - The aim of this study was to determine the antimicrobial resistance rates and the resistance genes associated with efflux pumps of Pseudomonas aeruginosa strains isolated from the patients who acquired lower respiratory tract infection (LRTI) in intensive care unit (ICU). Fifty P. aeruginosa strains isolated from the lower respiratory tract specimens of the patients who acquired LRTIs in ICU were included in this study. P. aeruginosa strains were isolated from tracheal aspirate (27), bronchoalveolar lavage (14) and sputum (9). The susceptibilities of the isolates were investigated by the disk diffusion method. Multiplex PCR assay was carried out for the detection of 13 antibiotic-resistance genes. Antimicrobial resistance rates of the isolates were found high and the highest resistance rate of the isolates studied was determined against to mezlocillin (50%) followed by norfloxacin (48%), ciprofloxacin (46%), meropenem (40%). Fourty three isolates (86%) were determined to carry one and more resistance genes. NfxB gene was most often determined in the genes that were investigated. The significant relation between the resistance to cefepime, piperacilline/tazobactam and the mexC gene, that between the resistance to mezlocillin, piperacilline/tazobactam, ceftazidime, cefepime and ampC genes, and that between the resistance to ciprofloxacin, norfloxacin and oprJ, oprN and nfxB genes was identified. Resistance caused by genes for carbapenemases, aminoglycoside modifying enzymes and other mechanisms were not identified in this study. Understanding the prevalence and mechanism of antimicrobial resistance in P. aeruginosa may help to select empirical therapy for nosocomial LRTIs due to P. aeruginosa in our ICU. PMID- 22086167 TI - A remodelling metric for angular fibre distributions and its application to diseased carotid bifurcations. AB - Many soft biological tissues contain collagen fibres, which act as major load bearing constituents. The orientation and the dispersion of these fibres influence the macroscopic mechanical properties of the tissue and are therefore of importance in several areas of research including constitutive model development, tissue engineering and mechanobiology. Qualitative comparisons between these fibre architectures can be made using vector plots of mean orientations and contour plots of fibre dispersion but quantitative comparison cannot be achieved using these methods. We propose a 'remodelling metric' between two angular fibre distributions, which represents the mean rotational effort required to transform one into the other. It is an adaptation of the earth mover's distance, a similarity measure between two histograms/signatures used in image analysis, which represents the minimal cost of transforming one distribution into the other by moving distribution mass around. In this paper, its utility is demonstrated by considering the change in fibre architecture during a period of plaque growth in finite element models of the carotid bifurcation. The fibre architecture is predicted using a strain-based remodelling algorithm. We investigate the remodelling metric's potential as a clinical indicator of plaque vulnerability by comparing results between symptomatic and asymptomatic carotid bifurcations. Fibre remodelling was found to occur at regions of plaque burden. As plaque thickness increased, so did the remodelling metric. A measure of the total predicted fibre remodelling during plaque growth, TRM, was found to be higher in the symptomatic group than in the asymptomatic group. Furthermore, a measure of the total fibre remodelling per plaque size, TRM/TPB, was found to be significantly higher in the symptomatic vessels. The remodelling metric may prove to be a useful tool in other soft tissues and engineered scaffolds where fibre adaptation is also present. PMID- 22086169 TI - Thymoma-associated progressive encephalomyelitis with rigidity and myoclonus successfully treated with thymectomy and intravenous immunoglobulin. PMID- 22086170 TI - PRaTo: a web-tool to select optimal primer pairs for qPCR. AB - An essential pre-requisite to perform sound quantitative real-time polymerase chain reaction (qPCR) assays is to design outstanding primer pairs. This means they must have a good efficiency and be not prone to produce multiple amplicons or primer dimer products. To circumvent these issues, several softwares are available to help primer design. Although satisfactory computer-aided primer design tools are available for standard PCR, less efforts were done to provide specific methods for selection of optimal primer pairs for qPCR. We have developed PRaTo a web-based tool that enables checking and ranking of primers pairs for their attitude to perform optimally and reliably when used in qPCR experiments. PRaTo is available at http://prato.daapv.unipd.it. PMID- 22086171 TI - DNA-binding properties of Smc6, a core component of the Smc5-6 DNA repair complex. AB - The Smc5-6 complex is an essential regulator of chromosome integrity and a key component of the DNA damage response. As an essential DNA repair factor, the Smc5 6 complex is expected to interact with DNA and/or chromatin during the execution of its functions. How the Smc6 protein promotes the binding of the Smc5-6 complex to DNA lesions is currently unknown. We show here that Smc6 is a strong DNA binding protein with a clear preference for single-stranded DNA substrates. Importantly, Smc6 associates with DNA in the absence of other Smc5-6 complex components and its activity is modulated by nucleotides. Our results also show that the minimal size of single-stranded DNA required for tight association with Smc6 is ~60 nucleotides in length. Taken together, our results suggest that Smc6 contributes to DNA repair in vivo by targeting the Smc5-6 complex to single stranded DNA substrates created during the processes of homologous recombination and/or DNA replication. PMID- 22086172 TI - Functional characterization of a synthetic abscisic acid analog with anti inflammatory activity on human granulocytes and monocytes. AB - The phytohormone abscisic acid (ABA), in addition to regulating several important physiological functions in plants, is also produced and released by human granulocytes and monocytes where it stimulates cell activities involved in the innate immune response. Here we describe the properties of an ABA synthetic analog that competes with the hormone for binding to human granulocyte membranes and to purified recombinant LANCL2 (the human ABA receptor) and inhibits several ABA-triggered inflammatory functions of granulocytes and monocytes in vitro: chemotaxis, phagocytosis, reactive oxygen species production and release of prostaglandin E(2) (PGE(2)) by human granulocytes, release of PGE(2) and of monocyte chemoattractant protein-1 by human monocytes. This observation provides a proof of principle that ABA antagonists may represent a new class of anti inflammatory agents. PMID- 22086173 TI - A fluorescence assay for elucidating the substrate specificities of deubiquitinating enzymes. AB - Ubiquitin C-terminal hydrolases (UCHs) are a representative family of deubiquitinating enzymes (DUBs), which specifically cleave ubiquitin (Ub) chains or extensions. Here we present a convenient method for characterizing the substrate specificities of various UCHs by fluorescently mutated Ub-fusion proteins (Ub(F45W)-Xaa) and di-ubiquitin chains (Ub(F45W)-diUb). After removal of the intact substrate by Ni(2+)-NTA affinity, the enzymatic activities of UCHs were quantitatively determined by recording fluorescence of the Ub(F45W) product. The results show that three UCHs, i.e. UCH-L1, UCH-L3 and UCH37/UCH-L5, are distinct in their substrate specificities for the Ub-fusions and diUb chains. This assay method may also be applied to study the enzymatic activities and substrate specificities of other DUBs. PMID- 22086174 TI - Expression of membrane-bound NPP-type ecto-phosphodiesterases in rat podocytes cultured at normal and high glucose concentrations. AB - The ecto-nucleotide pyrophosphatase/phosphodiesterase family (E-NPPs) contains two membrane-bound members: E-NPP1 and E-NPP3. These enzymes mediate hydrolysis of extracellular nucleotides and their abnormal expression may affect intracellular signal transduction pathways, leading to cellular dysfunction, e.g., insulin resistance. Podocytes are insulin-dependent glomerular epithelial cells that regulate the glomerular filtration rate. Pathology of podocytes is a hallmark of diabetic nephropathy. Here, we investigated the expressions of E-NPP1 and E-NPP3 and activity of E-NPP enzymes in rat podocytes cultured with 5mM (NG) or 30 mM glucose (HG). Insulin resistance was determined by measuring changes in [1,2-(3)H]-deoxy-D-glucose uptake in response to insulin. mRNAs of E-NPP1 and E NPP3 were detected within podocytes. The E-NPP expressions were confirmed at the protein level using western blot and immunofluorescence techniques. At NG, insulin (300 nM, 3 min) increased glucose uptake 1.5-fold; however, this effect was abolished at HG. The protein expressions of E-NPP1 and E-NPP3 were not affected at HG. The E-NPP activities were 24.68+/-0.72 and 26.51+/-1.55 nmol/min/mg protein at NG and HG, respectively. In conclusion, ecto-nucleotide pyrophosphatase/phosphodiesterase 1 and 3 are expressed on podocytes, but changes in expression of these enzymes are most likely not involved in etiology of insulin resistance in podocytes. PMID- 22086175 TI - Identification of reference genes for reverse transcription quantitative real time PCR normalization in pepper (Capsicum annuum L.). AB - Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) is a commonly used technology for gene expression and transcriptome analysis. Normalization is a process that is necessary to accurately analyze qRT-PCR data. Stability of reference gene expression is required for this process. Due to the large variation in expression levels of reference genes obtained from different experimental conditions, gene expression stabilities must be evaluated and identified in all experimental systems. In the present paper, the stability of the expression levels of seven potential reference genes in pepper are assessed using qRT-PCR analysis to determine optimal reference genes. These reference genes are evaluated in different pepper tissues, abiotic stress, and hormonal treatment samples. Three common statistical algorithms, geNorm, NormFinder, and BestKeeper, are used to identify expression stability and provide an accurate selection of reference genes. Two reference genes, beta tubulin and ubiquitin conjugating protein (UBI-3), showed high stability in sample pools with abiotic stress and hormonal treatments. Among the sample pools tested, UBI-3 and glyceraldehyde-3-phosphate dehydrogenase expression levels were the most stable in different tissues. Therefore, these reference genes are selected for qRT-PCR analysis under the experimental conditions tested in pepper. In contrast, ubiquitin-conjugating enzyme and actin genes are identified as the least stable reference genes in all the groups tested, confirming that they are not suitable for normalization. Validation of these candidate genes could provide useful guidelines for reference gene selection in qRT-PCR studies in pepper. PMID- 22086176 TI - Basophil-derived mouse mast cell protease 11 induces microvascular leakage and tissue edema in a mast cell-independent manner. AB - Mouse mast cell protease 11 (mMCP-11) is the most recently identified member of the mouse mast cell tryptase family. This tryptase is preferentially produced by basophils in contrast to other members that are expressed by mast cells but not basophils. Although blood-circulating basophils have long been considered as minor and redundant relatives of tissue-resident mast cells, recent studies illustrated that basophils and mast cells play distinct roles in vivo. To explore the in vivo role of basophil-derived mMCP-11, here we prepared recombinant mMCP 11 and its protease-dead mutant. Subcutaneous injection of the wild-type mMCP-11 but not the mutant induced edematous skin swelling with increased microvascular permeability in a dose-dependent manner. No apparent infiltration of proinflammatory cells including neutrophils and eosinophils was detected in the skin lesions. The cutaneous swelling was abolished by the pretreatment of mice with indomethacin, a cyclooxygenase inhibitor, suggesting the major contribution of prostaglandins to the microvascular leakage. Of note, the cutaneous swelling was elicited even in mast cell-deficient mice, indicating that mast cells are dispensable for the mMCP-11-induced cutaneous swelling. Thus, basophil-derived mMCP-11 can induce microvascular leakage via prostaglandins in a mast cell independent manner, and may contribute to the development of basophil-mediated inflammatory responses. PMID- 22086177 TI - Suppression of Nrdp1 toxicity by Parkin in Drosophila models. AB - Nrdp1 is a RING finger ubiquitin E3 ligase that interacts with Parkin, and promotes the degradation of Parkin, a causative protein for early onset Autosomal Recessive Juvenile Parkinsonism (AR-JP). To investigate if Nrdp1 plays a role in the pathogenesis of Parkinson's disease, we generated transgenic Drosophila that expressed Drosophila Nrdp1 (dNrdp1) and dNrdp1(D56V), an aspartic acid to valine mutant at residue 56 that disrupts its ring finger domain, resulting in impaired capacity to degrade its substrate ErbB3. Our data show that a pan-neuronal expression of transgenic dNrdp1 but not dNrdp1(D56V) mutant leads to the loss of dopaminergic neurons in brains, resulting in reduction of dopamine production. These flies also manifested decreased flight ability. Co-expression of human Parkin (hParkin) provides protection against toxicity induced by over-expression of dNrdp1, reversing the effects of dNrdp1 on death of dopaminergic neurons, reduction of dopamine production, and decreased flight ability. Taken together, we conclude that Nrdp1 plays a role in neurodegeneration and could be potentially targeted as a therapeutic strategy for Parkinson's disease. PMID- 22086178 TI - Cdc20 mediates D-box-dependent degradation of Sp100. AB - Cdc20 is a co-activator of the anaphase-promoting complex/cyclosome (APC/C complex), which recruits substrates at particular phases of the cell cycle and mediates their degradation. Sp100 is a PML-NB scaffold protein, which localizes to nuclear particles during interphase and disperses from them during mitosis, participates in viral resistance, transcriptional regulation, and apoptosis. However, its metabolism during the cell cycle has not yet been fully characterized. We found a putative D-box in Sp100 using the Eukaryotic Linear Motif (ELM) predictor database. The putative D-box of Sp100 was verified by mutational analysis. Overexpression of Cdc20 resulted in decreased levels of both endogenous Sp100 protein and overexpressed Sp100 mRNA in HEK 293 cells. Only an overexpressed D-box deletion mutant of Sp100 accumulated in HEK293 cells that also overexpressed Cdc20. Cdc20 knockdown by cdc20 specific siRNA resulted in increased Sp100 protein levels in cells. Furthermore, we discovered that the Cdc20 mediated degradation of Sp100 is diminished by the proteasome inhibitor MG132, which suggests that the ubiquitination pathway is involved in this process. However, unlike the other Cdc20 substrates, which display oscillating protein levels, the level of Sp100 protein remains constant throughout the cell cycle. Additionally, both overexpression and knockdown of endogenous Sp100 had no effect on the cell cycle. Our results suggested that sp100 is a novel substrate of Cdc20 and it is degraded by the ubiquitination pathway. The intact D-box of Sp100 was necessary for this process. These findings expand our knowledge of both Sp100 and Cdc20 as well as their role in ubiquitination. PMID- 22086179 TI - Methionine sulfoxide reductase A regulates cell growth through the p53-p21 pathway. AB - MsrA is an oxidoreductase that catalyzes the stereospecific reduction of methionine-S-sulfoxide to methionine. Although MsrA is well-characterized as an antioxidant and has been implicated in the aging process and cellular senescence, its roles in cell proliferation are poorly understood. Here, we report a critical role of MsrA in normal cell proliferation and describe the regulation mechanism of cell growth by this protein. Down-regulation of MsrA inhibited cell proliferation, but MsrA overexpression did not promote it. MsrA deficiency led to an increase in p21, a major cyclin-dependent kinase inhibitor, thereby causing cell cycle arrest at the G(2)/M stage. While protein levels of p53 were not altered upon MsrA deficiency, its acetylation level was significantly elevated, which subsequently activated p21 transcription. The data suggest that MsrA is a regulator of cell growth that mediates the p53-p21 pathway. PMID- 22086180 TI - Echocardiographic risk stratification of fetuses with sacrococcygeal teratoma and twin-reversed arterial perfusion. AB - OBJECTIVE: To evaluate pre-intervention echocardiographic parameters of cardiac function in fetuses who survive without hydrops as compared to fetuses who develop hydrops or perinatal death in the setting of sacrococcygeal teratoma (SCT) and twin-reversed arterial perfusion sequence (TRAP). METHODS: Clinical, echocardiographic and sonographic data of fetuses with SCT or TRAP during 1999 2009 were reviewed retrospectively. Measurements of cardiothoracic ratio (CTR), cardiac dimension Z-scores, combined ventricular output (CVO), valvular regurgitation, and cardiovascular profile scores (CVPS) were obtained. RESULTS: In total, 19 fetuses (11 SCT, 8 TRAP) met the inclusion criteria and 26 detailed fetal echocardiographic studies were reviewed. Outcome was poor in 7 pregnancies (group A) and good in 12 (group B). Group A had worse CVPS (8.5 vs. 10, p < 0.01) and higher CTR (0.37 vs. 0.30, p = 0.04). At least one of the following was present in each group A fetus: CTR >0.5, CVO >550 ml/min/kg, tricuspid or mitral regurgitation, or mitral valve Z-score >2. No group B fetus had any of these abnormalities. No fetus in either group had abnormal venous Doppler waveforms at presentation. CONCLUSIONS: Fetal echocardiography can identify abnormalities of cardiac size and systolic, but not diastolic, function in all fetuses who subsequently died or developed hydrops. PMID- 22086181 TI - Dissipation of chlorantraniliprole in tomato fruits and soil. AB - The main objective of this study was to understand the residue and persistence behaviour of new insecticide chlorantraniliprole in tomato fruit and soil samples. Its residue was analyzed by HPLC and it dissipated in tomato fruit and soil following first order kinetics. The results showed half life (t(1/2)) value of 3.30 and 3.66 days for chlorantraniliprole in tomato fruit and soil, respectively. According to maximum residue limit (MRL) the pre-harvest interval (PHI) of chlorantraniliprole on tomato was 8-days after the treatment. PMID- 22086182 TI - Estimation of indoxacarb residues by QuEChERS technique and its degradation pattern in cabbage. AB - Indoxacarb residues were estimated by employing standardized QuEChERS technique in cabbage following three applications of Avant(R) 14.8 EC @ 52.2 and 104.4 g a.i. ha(-1). The average recoveries of indoxacarb on cabbage for fortification levels of 0.01, 0.05 and 0.1 mg kg(-1) were observed to be 83.93, 89.86 and 95.40%, respectively, with relative standard deviation of 1.21, 1.53 and 2.23. The method was also validated with respect to parameters of linearity, precision and limit of quantification (LOQ). The LOQ for cabbage was found to be 0.01 mg kg(-1). The average initial deposits of indoxacarb on cabbage were observed to be 0.18 and 0.39 mg kg(-1), respectively, at single and double the application rate. These indoxacarb residues dissipated below its LOQ of 0.01 mg kg(-1)after 7 and 10 days, respectively, at single and double dosages. Half-life of indoxacarb was observed to be 2.88 and 1.92 days, respectively, at recommended and double the recommended dosages. PMID- 22086183 TI - Pinus densiflora leaf essential oil induces apoptosis via ROS generation and activation of caspases in YD-8 human oral cancer cells. AB - The leaf of Pinus (P.) densiflora, a pine tree widely distributed in Asian countries, has been used as a traditional medicine. In the present study, we investigated the anticancer activity of essential oil, extracted by steam distillation, from the leaf of P. densiflora in YD-8 human oral squamous cell carcinoma (OSCC) cells. Treatment of YD-8 cells with P. densiflora leaf essential oil (PLEO) at 60 ug/ml for 8 h strongly inhibited proliferation and survival and induced apoptosis. Notably, treatment with PLEO led to generation of ROS, activation of caspase-9, PARP cleavage, down-regulation of Bcl-2, and phosphorylation of ERK-1/2 and JNK-1/2 in YD-8 cells. Treatment with PLEO, however, did not affect the expression of Bax, XIAP and GRP78. Importantly, pharmaco-logical inhibition studies demonstrated that treatment with vitamin E (an anti-oxidant) or z-VAD-fmk (a pan-caspase inhibitor), but not with PD98059 (an ERK-1/2 inhibitor) or SP600125 (a JNK-1/2 inhibitor), strongly suppressed PLEO-induced apoptosis in YD-8 cells and reduction of their survival. Vitamin E treatment further blocked activation of caspase-9 and Bcl-2 down-regulation induced by PLEO. Thus, these results demonstrate firstly that PLEO has anti proliferative, anti-survival and pro-apoptotic effects on YD-8 cells and the effects are largely due to the ROS-dependent activation of caspases. PMID- 22086184 TI - The association between income source and met need among community mental health service users in Ontario, Canada. AB - We examined income source and match between recommended and received care among users of community mental health services. We conducted a secondary analysis of needs-based planning data on adults in Ontario community mental health programs from 2000 to 2002. The outcome was whether clients were severely underserved (yes/no) based on the match between level of care recommended and received. A logistic regression model investigated if income source predicted this outcome. 13% of clients were severely underserved. Over 40% were on public assistance and they had a higher risk of being severely undeserved than the others. Men were at greater risk. One aim of mental health reform is to increase access to care for vulnerable individuals. The finding that among users of community mental health services, individuals with public assistance income support are most vulnerable to being severely underserved should be considered by service planners and providers. PMID- 22086185 TI - Downregulation of EphA2 expression suppresses the growth and metastasis in squamous-cell carcinoma of the head and neck in vitro and in vivo. AB - PURPOSE: Our previous study has revealed that EphA2 overexpression is significantly associated with aggressive behavior and poor prognosis in patients with squamous-cell carcinoma of the head and neck (SCCHN). However, the function of EphA2 in tumorigenesis and cervical lymph node metastasis of SCCHN has never been elucidated in vivo. METHODS: EphA2 was knocked down in SCCHN cell lines. CCK 8 assays, fluorescence-activated cell sorting analysis, invasion and migration assays were performed in vitro. In vivo tumorigenicity assays were performed, and the impact on cervical lymph node metastasis was evaluated. RESULTS: The present investigation demonstrated that suppression of EphA2 resulted in a significant inhibition of proliferation, migration, invasion of SCCHN cells in vitro and markedly diminished their tumorigenicity and lymph node metastasis in vivo. CONCLUSIONS: These results suggest that EphA2 plays a critical role in SCCHN growth and metastasis and may be a promising therapeutic target to prevent the progression of SCCHN. PMID- 22086186 TI - Influence of dendrimers on red blood cells. AB - Dendrimers, highly branched macromolecules with a specific size and shape, provide many exciting opportunities for biomedical applications. However, most dendrimers demonstrate toxic and haemolytic activity because of their positively charged surface. Masking the peripheral cationic groups by coating them with biocompatible molecules is a method to reduce it. It was proven that modified dendrimers can even diminish haemolytic activity of encapsulated drugs. Experiments confirmed that anionic dendrimers are less haemotoxic than cationic ones. Due to the high affinity of dendrimers for serum proteins, presence of these components in an incubation buffer might also influence red blood cell (RBC)-dendrimer interactions and decrease the haemolysis level. Generally, haemotoxicity of dendrimers is concentration-, generation-, and time-dependent. Various changes in the RBCs' shape in response to interactions with dendrimers have been observed, from echinocytic transformations through cell aggregation to cluster formation, depending on the dendrimer's type and concentration. Understanding the physical and chemical origins of dendrimers' influences on RBCs might advance scientists' ability to construct dendrimers more suitable for medical applications. PMID- 22086187 TI - Anharmonic nuclear dynamics in the mixed quantum-classical limit. AB - This study employs mixed quantum-classical dynamics (MQCD) formalism to evaluate the linear electronic dipole moment time correlation function (DMTCF) in which a Morse oscillator serves to model the associated vibrations in a mixed quantum classical (MQC) environment. While the main purpose of this work is to study the applicability of MQCD formalism to anharmonic systems in condensed phase, approximate schemes to physically evaluate the mathematically divergent integrals have been developed in order to deal with the essential singularities that arise while evaluating the Morse oscillator canonical partition function and the DMTCF in MQC systems in the classical limit. The motivation for numerically and analytically evaluating these divergent integrals is that a partition function of any system should lead to a finite value at any temperature and therefore this divergence is unphysical. Additionally, since a partition function is to signify the number of accessible states to the system at hand, divergent results are not physically acceptable. As such, straightforward approximate analytic expressions, at different levels of rigor, for both the classical Morse oscillator partition function and the DMTCF in MQC systems are derived, for the first time. Calculations of Morse oscillator partition function values using different approaches at various temperatures for CO, HCl, and I(2) molecules, showing good results, are presented to test the expressions derived herein. It is found that this divergence, due to singularity, diminishes upon lowering the temperature and only arises at high temperatures. The gradual diminishing of the singularity upon lowering the temperature is sensible since the Morse potential fits the parabolic potential at low temperatures. Model calculations and discussion of the DMTCF and linear absorption spectra in MQC systems using the molecular constants of CO molecule are provided. The linear absorption lineshape is derived by two methods, one of which is asymptotic expansion. PMID- 22086189 TI - The influence of dose heterogeneity on tumour control probability in fractionated radiation therapy. AB - Theoretical modelling of tumour control probability (TCP) with respect to non uniformity in the dose to the tumour, alternate fractionation schemes and tumour kinetics is a very useful tool for assessment of the influence of changes in dosimetric or radiobiological factors on the outcome of the treatment. Various attempts have been made to also include effects from non-uniform dose to the tumour volume, but the problem has not been fully solved and many factors were totally neglected or not accurately taken into account. This paper presents derivations of analytical expressions of TCP for macroscopic inter-cell dose variations and for random inter-fractional variations in average tumour dose, based on binomial statistics for the TCP and the well-known linear quadratic model for the cell survival. Numerical calculations have been performed to validate the analytical expressions. An analysis of the influence of the deterministic and stochastic heterogeneity in dose delivery on the TCP was performed. The precision requirements in dose delivery are discussed briefly with the support of the presented results. The main finding of this paper is that it is primarily the shape of the cell survival curve that governs how the response is affected by macroscopic dose variations. The analytical expressions for TCP accounting for heterogeneity in dose can quite well describe the TCP for varying dose from cell to cell and random dose in each fraction. An increased TCP is seen when a large number of fractions are used and the variations in dose to the cells are rather high for tissues with low alpha/beta. PMID- 22086188 TI - Nematode modulation of inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is a chronic disease arising due to a culmination of genetic, environmental, and lifestyle-associated factors and resulting in an excessive pro-inflammatory response to bacterial populations in the gastrointestinal tract. The prevalence of IBD in developing nations is relatively low, and it has been proposed that this is directly correlated with a high incidence of helminth infections in these areas. Gastrointestinal nematodes are the most prevalent parasitic worms, and they efficiently modulate the immune system of their hosts in order to establish chronic infections. Thus, they may be capable of suppressing unrelated inflammation in disorders such as IBD. This review describes how nematodes, or their products, suppress innate and adaptive pro-inflammatory immune responses and how the mechanisms involved in the induction of anti-nematode responses regulate colitis in experimental models and clinical trials with IBD patients. We also discuss how refinement of nematode derived therapies should ultimately result in the development of potent new therapeutics of clinical inflammatory disorders. PMID- 22086190 TI - Is the increase in bone mineral density after hip resurfacing uniform across the femoral neck? PMID- 22086191 TI - On the nature of semantic constraints on lexical access. AB - We present two eye-tracking experiments that investigate lexical frequency and semantic context constraints in spoken-word recognition in German. In both experiments, the pivotal words were pairs of nouns overlapping at onset but varying in lexical frequency. In Experiment 1, German listeners showed an expected frequency bias towards high-frequency competitors (e.g., Blume, 'flower') when instructed to click on low-frequency targets (e.g., Bluse, 'blouse'). In Experiment 2, semantically constraining context increased the availability of appropriate low-frequency target words prior to word onset, but did not influence the availability of semantically inappropriate high-frequency competitors at the same time. Immediately after target word onset, however, the activation of high-frequency competitors was reduced in semantically constraining sentences, but still exceeded that of unrelated distractor words significantly. The results suggest that (1) semantic context acts to downgrade activation of inappropriate competitors rather than to exclude them from competition, and (2) semantic context influences spoken-word recognition, over and above anticipation of upcoming referents. PMID- 22086192 TI - Pancreatic cancer is not noble. PMID- 22086193 TI - OCT4 pseudogenes present in human leukemia cells. AB - The transcription factor OCT4 is expressed in embryonic stem cells (ESCs) and has been considered as a main regulator in maintaining pluripotency of ESCs. Several studies have showed OCT4 expression in human solid tumor and adult stem or progenitor cells. However, whether OCT4 is expressed in normal hematopoietic system including the peripheral blood and bone marrow remains controversial. Furthermore, the functional expression of OCT4 in leukemia cells and its potential significance in leukemia studies have been poorly defined. The aim of this study was to examine and analyze the genuine expression of OCT4 in human leukemia cells by means of RT-PCR, flow cytometry, PCR product sequencing and alignment with NCBI BLAST and DNAMAN software. The full lengths of the putative OCT4 genes were amplified in 2/9 leukemia cell lines and 7/49 leukemia patients' samples. However, many base mutations in putative OCT4 positive samples were found. Sequence alignment analysis showed a higher similarity between the putative OCT4 PCR products and the pseudogenes in chromosomes 1 and 8. The positive rates of OCT4 protein detected with flow cytometry were low, and almost all of them were less than 10% of positivity. A very small fraction of leukemia stem cells with OCT4 protein expression was found. We conclude that OCT4 pseudogenes in chromosomes 1 and 8 present in the panel of leukemia cells tested and the OCT4 protein is rarely detected with flow cytometry in leukemia cells. PMID- 22086194 TI - Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury. AB - Preconditioning induces ischemic tolerance, which confers robust protection against ischemic damage. We show marked protection with polyinosinic polycytidylic acid (poly-IC) preconditioning in three models of murine ischemia reperfusion injury. Poly-IC preconditioning induced protection against ischemia modeled in vitro in brain cortical cells and in vivo in models of brain ischemia and renal ischemia. Further, unlike other Toll-like receptor (TLR) ligands, which generally induce significant inflammatory responses, poly-IC elicits only modest systemic inflammation. Results show that poly-IC is a new powerful prophylactic treatment that offers promise as a clinical therapeutic strategy to minimize damage in patient populations at risk of ischemic injury. PMID- 22086195 TI - Visualizing cell death in experimental focal cerebral ischemia: promises, problems, and perspectives. AB - One of the hallmarks of stroke pathophysiology is the widespread death of many different types of brain cells. As our understanding of the complex disease that is stroke has grown, it is now generally accepted that various different mechanisms can result in cell damage and eventual death. A plethora of techniques is available to identify various pathological features of cell death in stroke; each has its own drawbacks and pitfalls, and most are unable to distinguish between different types of cell death, which partially explains the widespread misuse of many terms. The purpose of this review is to summarize the standard histopathological and immunohistochemical techniques used to identify various pathological features of stroke. We then discuss how these methods should be properly interpreted on the basis of what they are showing, as well as advantages and disadvantages that require consideration. As there is much interest in the visualization of stroke using noninvasive imaging strategies, we also specifically discuss how these techniques can be interpreted within the context of cell death. PMID- 22086196 TI - Kollidon VA64, a membrane-resealing agent, reduces histopathology and improves functional outcome after controlled cortical impact in mice. AB - Loss of plasma membrane integrity is a feature of acute cellular injury/death in vitro and in vivo. Plasmalemma-resealing agents are protective in acute central nervous system injury models, but their ability to reseal cell membranes in vivo has not been reported. Using a mouse controlled cortical impact (CCI) model, we found that propidium iodide-positive (PI+) cells pulse labeled at 6, 24, or 48 hours maintained a degenerative phenotype and disappeared from the injured brain by 7 days, suggesting that plasmalemma permeability is a biomarker of fatal cellular injury after CCI. Intravenous or intracerebroventricular administration of Kollidon VA64, poloxamer P188, or polyethylene glycol 8000 resealed injured cell membranes in vivo (P<0.05 versus vehicle or poloxamer P407). Kollidon VA64 (1 mmol/L, 500 MUL) administered intravenously to mice 1 hour after CCI significantly reduced acute cellular degeneration, chronic brain tissue damage, brain edema, blood-brain barrier damage, and postinjury motor deficits (all P<0.05 versus vehicle). However, VA64 did not rescue pulse-labeled PI+ cells from eventual demise. We conclude that PI permeability within 48 hours of CCI is a biomarker of eventual cell death/loss. Kollidon VA64 reduces secondary damage after CCI by mechanisms other than or in addition to resealing permeable cells. PMID- 22086197 TI - Sequential activation of hypoxia-inducible factor 1 and specificity protein 1 is required for hypoxia-induced transcriptional stimulation of Abcc8. AB - Cerebral ischemia causes increased transcription of sulfonylurea receptor 1 (SUR1), which forms SUR1-regulated NC(Ca-ATP) channels linked to cerebral edema. We tested the hypothesis that hypoxia is an initial signal that stimulates transcription of Abcc8, the gene encoding SUR1, via activation of hypoxia inducible factor 1 (HIF1). In the brain microvascular endothelial cells, hypoxia increased SUR1 abundance and expression of functional SUR1-regulated NC(Ca-ATP) channels. Luciferase reporter activity driven by the Abcc8 promoter was increased by hypoxia and by coexpression of HIF1alpha. Surprisingly, a series of luciferase reporter assays studying the Abcc8 promoter revealed that binding sites for specificity protein 1 (Sp1), but not for HIF, were required for stimulation of Abcc8 transcription by HIF1alpha. Luciferase reporter assays studying Sp1 promoters of three species, and chromatin immunoprecipitation analysis in rats after cerebral ischemia, indicated that HIF binds to HIF-binding sites on the Sp1 promoter to stimulate transcription of the Sp1 gene. We conclude that sequential activation of two transcription factors, HIF and Sp1, is required to stimulate transcription of Abcc8 following cerebral ischemia. Sequential gene activation in cerebral ischemia provides a plausible molecular explanation for the prolonged treatment window observed for inhibition of the end-target gene product, SUR1, by glibenclamide. PMID- 22086198 TI - A perspective on the mobilization, localization and delivery of molecules in the crowded bacterial cytoplasm. AB - It has been assumed that diffusion of molecules in the bacterial cytoplasm is the mechanism that moves molecules in the absence of cytoplasmic streaming. However, is there an undiscovered mechanism present that mobilizes cytoplasm and its molecular contents, and delivers tRNAs to specific ribosomes at specific bacterial cytoplasmic locations? Mobilization of specific tRNA (and also mRNA transcripts and ribosomes) and cell division proteins to specific intracellular locations may suggest that instructions and/or mechanism(s) are needed. The alternative is that molecular crowding in the cytoplasm is sufficient for gentle contact between mRNA, ribosomes and tRNA. Or is it plausible that the bacterial cytoplasm (and its contents) are mobilized with the outcome being more gentle collisions between molecules than by a diffusion only mechanism? One hypothesis is that cytoplasmic and molecule mobilization and spatial organization are possibly driven by the photons in thermal infrared (IR) radiation and generation of exclusion zone (EZ) water in the cytoplasm. PMID- 22086200 TI - Women with gestational diabetes develop glucose intolerance with high frequency within one year postpartum. AB - OBJECTIVE: To investigate the incidence of glucose intolerance postpartum in women with gestational diabetes (GDM) and assess body weight, cholesterol and triglyceride concentrations after delivery. METHODS: This was a study of an initial cohort of 100 women with GDM who were tested at 6 weeks, 6 months, and 1 year postpartum. Postpartum evaluations were glucose tolerance, weight and cholesterol and triglycerides. RESULTS: Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was present in 36.5% of 52 participants who were assessed at 6 weeks postpartum and diabetes in 17.3%; the remaining 48 women failed to return for the 3 evaluations. By 6 months, IFG/IGT was demonstrated in 55.8% and diabetes in 32.7% of the women. At 1 year, 46.2% exhibited IFG/IGT and 48% diabetes. Moreover, the weight was higher in those women who presented IFG/IGT (75.5 +/- 15.2 kg, mean +/- SD) and diabetes (79.0 +/- 16.2 kg) compared with those who had normal glucose tolerance (65.3 +/- 14.5 kg; p < 0.05). In addition, triglycerides were higher in mothers with glucose intolerance (181.3 +/ 85.9 mg/dl in IFG/IGT and 230.9 +/- 90.9 mg/dl in diabetes) than in women with normal glycemia (147.8 +/- 11.2 mg/dl; p < 0.05). CONCLUSION: We demonstrated an increased incidence of women exhibiting glucose intolerance within 1 year postpartum, mainly in those who remained obese. PMID- 22086201 TI - Hippocampal atrophy as late sequela of carbon monoxide poisoning. PMID- 22086199 TI - Determinants of short- and long-term outcome in patients undergoing simultaneous resection of colorectal cancer and synchronous colorectal liver metastases. AB - PURPOSE: The optimal surgical strategy for patients presenting with colorectal liver metastases has yet to be determined. Short- and long-term outcomes must be considered if simultaneous resection of primary and liver metastases is to gain acceptance. We examine the prognostic value of patient and tumour characteristics in predicting short- and long-term outcomes following simultaneous resection for synchronous disease. METHODS: Forty-six patients undergoing simultaneous resection between April 2002 and June 2010 in a single institution were included. Patient characteristics included preoperative ASA grade and POSSUM. Tumour characteristics included TNM stage, Petersen Index and the Clinical Risk Score. RESULTS: There were no postoperative deaths. The most common complications were atrial fibrillation (seven patients) and pneumonia (seven patients). Mean hospital stay with an uncomplicated postoperative recovery was 11 days versus 17 days with complicated recovery. Age (p = 0.015), ASA grade (p = 0.010) and POSSUM score (p = 0.032) were associated with postoperative complications. No pathological characteristics of the primary or secondary tumours related to surgical morbidity. Median follow-up was 37 months (5-87) during which 24 patients died, 23 from cancer. Twenty-seven had disease recurrence. N stage of the primary (p = 0.035), high-risk Petersen Index of the primary (p = 0.010) and Clinical Risk Score >= 3 (p = 0.005) were associated with poorer recurrence-free and cancer-specific survival. CONCLUSIONS: Post operative morbidity was determined by patient factors rather than operative or tumour characteristics. In addition to the Clinical Risk Score, pathological characteristics of the primary are important determinants of long-term outcome following simultaneous resection for synchronous disease. PMID- 22086203 TI - Photo-induced DNA cleavage activity and remarkable photocytotoxicity of lanthanide(III) complexes of a polypyridyl ligand. AB - Lanthanide(III) complexes [Ln(pyphen)(acac)(2)(NO(3))] (1, 2), [Ln(pydppz)(acac)(2)(NO(3))] (3, 4) and [La(pydppz)(anacac)(2)(NO(3))] (5), where Ln is La(III) (in 1, 3, 5) and Gd(III) (in 2, 4), pyphen is 6-(2-pyridyl)-1,10 phenanthroline, pydppz is 6-(2-pyridyl)-dipyrido[3,2-a:2',3'-c]phenazine, anacac is anthracenylacetylacetonate and acac is acetylacetonate, were prepared, characterized and their DNA photocleavage activity and photocytotoxicity studied. The crystal structure of complex 2 displays a GdO(6)N(3) coordination. The pydppz complexes 3-5 show an electronic spectral band at ~390 nm in DMF. The La(III) complexes are diamagnetic, while the Gd(III) complexes are paramagnetic with seven unpaired electrons. The molar conductivity data suggest 1 : 1 electrolytic nature of the complexes in aqueous DMF. They are avid binders to calf thymus DNA giving K(b) in the range of 5.4 * 10(4)-1.2 * 10(6) M(-1). Complexes 3-5 efficiently cleave supercoiled DNA to its nicked circular form in UV-A light of 365 nm via formation of singlet oxygen ((1)O(2)) and hydroxyl radical (HO) species. Complexes 3-5 also exhibit significant photocytotoxic effect in HeLa cancer cells giving respective IC(50) value of 0.16(+/-0.01), 0.15(+/-0.01) and 0.26+/-(0.02) MUM in UV-A light of 365 nm, while they are less toxic in dark with an IC(50) value of >3 MUM. The presence of an additional pyridyl group makes the pydppz complexes more photocytotoxic than their dppz analogues. FACS analysis of the HeLa cells treated with complex 4 shows apoptosis as the major pathway of cell death. Nuclear localization of complex 5 having an anthracenyl moiety as a fluorophore is evidenced from the confocal microscopic studies. PMID- 22086204 TI - RNA interference-mediated silencing of SOCS-1 via lentiviral vector promotes apoptosis of alveolar epithelial cells in vitro. AB - Suppressor of cytokine signaling-1 (SOCS1) is a protein that negatively regulates cytokine and growth factor signaling. However, little is known regarding the precise role it plays in idiopathic pulmonary fibrosis. The aim of the present study was to construct a recombinant lentiviral vector for RNA interference targeting the SOCS1 gene and to detect the expression in human alveolar epithelial cells. A lentiviral vector-mediated RNA interference method was used to establish a SOCS1-negative cell line of alveolar origin (A549). Three pairs of complementary small hairpin RNA (shRNA) oligonucleotides targeting the SOCS1 gene were designed, synthesized and inserted into the pPll3.7 vector. Packaged lentivirus particles were obtained after 48 h, and the supernatant was used to transfect the human alveolar epithelial cell line A549. The expression of the SOCS1 protein was detected by Western blotting. MTT assay was used to detect the cell proliferation of alveolar epithelial cells with SOCS1 knockdown. The recombinant plasmids were confirmed by sequencing. The lentivirus-containing supernatant effectively infected the A549 cell line, and the expression of SOCS1 protein was inhibited, which was confirmed by Western blotting in the target cells. MTT assay indicated the inhibition effect for cell proliferation of A549 cells in the SOCS1-RNA interference group, compared to the control group with no interference-mediated silencing of the SOCS1 gene. A lentiviral vector for RNA interference targeting the SOCS1 gene was successfully constructed, and cell survival tests showed that knockdown of the SOCS1 gene promotes the apoptosis of alveolar cells. PMID- 22086205 TI - Development of the zebrafish myoseptum with emphasis on the myotendinous junction. AB - Zebrafish myosepta connect two adjacent muscle cells and transmit muscular forces to axial structures during swimming via the myotendinous junction (MTJ). The MTJ establishes transmembrane linkages system consisting of extracellular matrix molecules (ECM) surrounding the basement membrane, cytoskeletal elements anchored to sarcolema, and all intermediate proteins that link ECM to actin filaments. Using a series of zebrafish specimens aged between 24 h post-fertilization and 2 years old, the present paper describes at the transmission electron microscope level the development of extracellular and intracellular elements of the MTJ. The transverse myoseptum development starts during the segmentation period by deposition of sparse and loosely organized collagen fibrils. During the hatching period, a link between actin filaments and sarcolemma is established. The basal lamina underlining sarcolemma is well differentiated. Later, collagen fibrils display an orthogonal orientation and fibroblast-like cells invade the myoseptal stroma. A dense network of collagen fibrils is progressively formed that both anchor myoseptal fibroblasts and sarcolemmal basement membrane. The differentiation of a functional MTJ is achieved when sarcolemma interacts with both cytoskeletal filaments and extracellular components. This solid structural link between contractile apparatus and ECM leads to sarcolemma deformations resulting in the formation of regular invaginations, and allows force transmission during muscle contraction. This paper presents the first ultrastructural atlas of the zebrafish MTJ development, which represents an useful tool to analyse the mechanisms of the myotendinous system formation and their disruption in muscle disorders. PMID- 22086208 TI - Effects of tourism and topography on vegetation diversity in the subalpine meadows of the Dongling Mountains of Beijing, China. AB - Subalpine meadows in the Dongling Mountains (located at E115o26'-115o40', N40o00' 40o05') of Beijing, China are important for tourism and the provision of ecosystem services. However, because of poor management serious degradation has occurred on these subalpine meadows. The aim of this paper is to present a quantitative analysis of effects of tourism disturbance and topography on the status and diversity of montane meadow communities and to provide direction for improved management. Sixty quadrats of 2 * 2 m(2) along 10 transects were set up to collect data on site characteristics and vegetation status. The relationships between community composition and structure, species diversity, and tourism disturbance and topographic variables were analyzed by multivariate methods (TWINSPAN and CCA). The results showed that eight meadow communities were identified by TWINSPAN. Most of them were seriously degraded. The first CCA axis identified an elevation and tourism disturbance intensity gradient, which illustrated that tourism disturbance and elevation were most important factors influencing meadow types, composition and structure. Some resistant species and response species to tourism disturbance were identified and can be used as indicator species of tourism disturbance. Species richness, heterogeneity and evenness were closely related to tourism disturbance and elevation. It is concluded that tourism disturbance must be controlled to enable grassland rehabilitation to occur in the meadows. Measures of effective management of the meadows were discussed. PMID- 22086207 TI - Development and validation of an aquatic Fine Sediment Biotic Index. AB - The Fine Sediment Biotic Index (FSBI) is a regional, stressor-specific biomonitoring index to assess fine sediment (<2 mm) impacts on macroinvertebrate communities in northwestern US streams. We examined previously collected data of benthic macroinvertebrate assemblages and substrate particle sizes for 1,139 streams spanning 16 western US Level III Ecoregions to determine macroinvertebrate sensitivity (mostly at species level) to fine sediment. We developed FSBI for four ecoregion groupings that include nine of the ecoregions. The grouping were: the Coast (Coast Range ecoregion) (136 streams), Northern Mountains (Cascades, N. Rockies, ID Batholith ecoregions) (428 streams), Rockies (Middle Rockies, Southern Rockies ecoregions) (199 streams), and Basin and Plains (Columbia Plateau, Snake River Basin, Northern Basin and Range ecoregions) (262 streams). We excluded rare taxa and taxa identified at coarse taxonomic levels, including Chironomidae. This reduced the 685 taxa from all data sets to 206. Of these 93 exhibited some sensitivity to fine sediment which we classified into four categories: extremely, very, moderately, and slightly sensitive; containing 11, 22, 30, and 30 taxa, respectively. Categories were weighted and a FSBI score calculated by summing the sensitive taxa found in a stream. There were no orders or families that were solely sensitive or resistant to fine sediment. Although, among the three orders commonly regarded as indicators of high water quality, the Plecoptera (5), Trichoptera (3), and Ephemeroptera (2) contained all but one of the species or species groups classified as extremely sensitive. Index validation with an independent data set of 255 streams found FSBI scores to accurately predict both high and low levels of measured fine sediment. PMID- 22086206 TI - Biological aspects of angiogenesis in multiple myeloma. AB - Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant expansion of malignant plasma cells within the bone marrow (BM). One of the hallmarks of this disease is the close interaction between myeloma cells and neighboring cells within the BM. Angiogenesis, through the activation of endothelial cells, plays an essential role in MM biology. In the current review, we describe the angiogenesis process in MM by identifying the interacting cells, the pro- and anti-angiogenic cytokines modulated, and the extracellular matrix degrading proteases liable to participate in the pathophysiology. Finally, we highlight the impact of hypoxia (through hypoxia-inducible factor-1) and constitutive activation of nuclear factor-kappaB in this tumor-induced neo vascularization. PMID- 22086209 TI - Concentrations of PM(2.5) mass and components in residential and non-residential indoor microenvironments: the Sources and Composition of Particulate Exposures study. AB - Although short in duration, air pollutant exposures occurring in non-residential microenvironments (MEs), including restaurants, vehicles and commercial locations, can represent a large fraction of total personal exposures. For the Sources and Composition of Particulate Exposures study, a novel compact sampling system was developed, facilitating simultaneous measurement of highly speciated PM(2.5) mass in a range of commercial and residential locations. This sampler also included 1-min measurements of PM(2.5) mass and ultrafine particle (UFP) counts. Sampling was conducted in a number of MEs (retail stores, restaurants and vehicles) throughout Atlanta. Chemically resolved particulate measurements in these locations are of interest for both exposure scientists and epidemiologists but have typically not been conducted because of logistical constraints associated with sampling these trace constituents. We present measurements from a non-random sample of locations that are limited in their generalizability but provide several promising hypothesis-generating results. PM(2.5) mass concentrations greater than 100 MUg/m(3), and UFPs>10(5) particles /cm(3) were measured during several events in the restaurant and vehicle. Somewhat unexpectedly, the grocery store ME, along with the restaurant and vehicle, also had the highest levels of elemental carbon (EC), organic carbon (OC) and most elements. In-vehicle concentrations of soil-related elements (Al, Ca, Fe, K and Ti) and auto-related elements (EC, OC, Zn and Cu) were higher than those measured at a central ambient site. The lowest concentrations for most pollutants were found in the hospital and retail locations. It is questionable whether periodic, high PM concentrations in the grocery store and restaurant pose health risks for customers; however, individuals working in these locations may be exposed to levels of concern. PMID- 22086210 TI - Classification of G proteins and prediction of GPCRs-G proteins coupling specificity using continuous wavelet transform and information theory. AB - The coupling between G protein-coupled receptors (GPCRs) and guanine nucleotide binding proteins (G proteins) regulates various signal transductions from extracellular space into the cell. However, the coupling mechanism between GPCRs and G proteins is still unknown, and experimental determination of their coupling specificity and function is both expensive and time consuming. Therefore, it is significant to develop a theoretical method to predict the coupling specificity between GPCRs and G proteins as well as their function using their primary sequences. In this study, a novel four-layer predictor (GPCRsG_CWTIT) based on support vector machine (SVM), continuous wavelet transform (CWT) and information theory (IT) is developed to classify G proteins and predict the coupling specificity between GPCRs and G proteins. SVM is used for construction of models. CWT and IT are used to characterize the primary structure of protein. Performance of GPCRsG_CWTIT is evaluated with cross-validation test on various working dataset. The overall accuracy of the G proteins at the levels of class and family is 98.23 and 85.42%, respectively. The accuracy of the coupling specificity prediction varies from 74.60 to 94.30%. These results indicate that the proposed predictor is an effective and feasible tool to predict the coupling specificity between GPCRs and G proteins as well as their functions using only the protein full sequence. The establishment of such an accurate prediction method will facilitate drug discovery by improving the ability to identify and predict protein-protein interactions. GPCRsG_CWTIT and dataset can be acquired freely on request from the authors. PMID- 22086211 TI - Dietary L-glutamine supplementation improves pregnancy outcome in mice infected with type-2 porcine circovirus. AB - Porcine circovirus type 2 (PCV2) causes reproductive failure in swine. As glutamine can enhance immune function in animals, this study was conducted with mice to test the hypothesis that dietary glutamine supplementation will improve pregnancy outcome in PCV2-infected dams. Beginning on day 0 of gestation, mice were fed a standard diet supplemented with 1.0% L-glutamine or 1.22% L-alanine (isonitrogenous control). All mice were infected with PCV2 (2000 TCID50) on day 10 of gestation. On day 17 of gestation, six mice from each group were euthanized to obtain maternal tissues and fetuses for hematology and histopathology tests. The remaining mice continued to receive their respective diets supplemented with 1.0% L-glutamine or 1.22% L-alanine through lactation. The PCV2 virus was present in maternal samples (serum and lung) of most mice in the control group but was not detected in the glutamine-supplemented mice. Dietary glutamine supplementation reduced abortion, decreased fetal deaths, and enhanced neonatal survival. The glutamine treatment also reduced concentrations of interleukin-6, while increasing concentrations of tumor necrosis factor-alpha and C-reactive protein, in the maternal serum of mice. Furthermore, glutamine supplementation attenuated microscopic lesions in maternal tissues (lung, spleen, and liver). Collectively, these results indicate that dietary glutamine supplementation is beneficial for ameliorating reproductive failure in virus-infected mice. The findings support the notion that gestating dams require adequate amounts of dietary glutamine for the optimal survival and growth of embryos, fetuses, and neonates, and have important implications for nutritional support of mammals (including swine and humans) during gestation and lactation. PMID- 22086212 TI - The side chain of glutamine 13 is the acyl-donor amino acid modified by type 2 transglutaminase in subunit T of the native rabbit skeletal muscle troponin complex. AB - Subunit T of the native muscle troponin complex is a recognised substrate of transglutaminase both in vitro and in situ with formation of isopeptide bonds. Using a proteomic approach, we have now determined the precise site of in vitro labelling of the protein. A preparation of troponin purified from ether powder from mixed rabbit skeletal muscles was employed as transglutaminase substrate. The only isoform TnT2F present in our preparation was recognised as acyl substrate by human type 2 transglutaminase which specifically modified glutamine 13 in the N-terminal region. During the reaction, the troponin protein complex was polymerized. Results are discussed in relation to the structure of the troponin T subunit, in the light of the role of troponins in skeletal and cardiac muscle diseases, and to the rules governing glutamine side chain selection by tissue transglutaminase. PMID- 22086213 TI - The suppression of thymic stromal lymphopoietin expression by selenium. AB - Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis. Selenium (Se) has various effects such as antioxidant, antitumor, antiulcer, and anti-inflammatory effects. However, the effect of Se on the production of TSLP has not been clarified. Thus, we investigated how Se inhibits the production of TSLP in the human mast cell line, HMC-1 cells. Se suppressed the production and mRNA expression of TSLP in HMC-1 cells. The maximal inhibition rate of TSLP production by Se (10 MUM) was 59.14 +/- 1.10%. In addition, Se suppressed the nuclear factor-kappaB luciferase activity induced by phorbol myristate acetate plus A23187. In the activated HMC-1 cells, the activation of caspase-1 was increased; whereas the activation of caspase-1 was decreased by pretreatment with Se. These results suggest that Se can be used to treat inflammatory and atopic diseases through the suppression of TSLP. PMID- 22086214 TI - Food tolerance in patients submitted to gastric bypass: the importance of using an integrated and interdisciplinary approach. AB - BACKGROUND: Under the restrictive component, patients undergoing gastric bypass may have food intolerance with or without complications. METHODS: This study used quantitative, analytical, observational methodology with patients submitted to Roux-en-Y gastric bypass without the placement of a ring at Hospital Universitario do Rio Grande do Norte in the city of Natal, Brazil between July 2005 and August 2010. Out of 176 patients monitored after surgery by the interdisciplinary team, 47 took part in the study. Two questionnaires were applied to participants: one elaborated by Suter et al. and previously validated for assessment of food tolerance and another to characterize schooling and socioeconomic status. Evaluation of food tolerance considered patient satisfaction with eating, most accepted food types, and frequency of vomiting and/or regurgitation. After application of the first questionnaire, a score was generated, characterizing food intolerance. RESULTS: Of the 47 patients evaluated, 85.1% classified their degree of food satisfaction as good or excellent. Red meat was the most cited as being difficult to ingest (38.3%), representing a significant impact on overall tolerance level (P < 0.001); 48.9% of participants exhibited rare episodes of vomiting, which resulted in a mean food tolerance score of 23.02 (2.87 +/- SD). Moreover, socioeconomic status showed a significant correlation with tolerance level (P = 0.032). CONCLUSIONS: The degree of food tolerance observed in the study sample was better than that obtained in other investigations using similar methodology. The questionnaire proved to be useful in evaluating food quality and comparing postoperative results. Socioeconomic status was correlated with food tolerance level. PMID- 22086215 TI - Comparing quantile residual life functions by confidence bands. AB - In this article we present a nonparametric method for constructing confidence bands for the difference of two quantile residual life (qrl) functions. These bands provide evidence for two random variables ordering with respect to the qrl order. The comparison of qrl functions is of importance, specially in the treatment of cancer when there exists a possibility of benefiting from a new secondary therapy. A qrl function is the quantile of the remaining life of a surviving subject, as it varies with time. We show the applicability of this approach in Medicine and Ecology. A simulation study has been carried out to evaluate and illustrate the performance and the consistency of this new methodology. PMID- 22086216 TI - A deconvolution approach for PET-based dose reconstruction in proton radiotherapy. AB - Positron emitters are activated by proton beams in proton radiotherapy, and positron emission tomography (PET) images can thus be used for dose verification. Since a PET image is not directly proportional to the delivered radiation dose distribution, predicted PET images are compared to measured PET images and an agreement of both indicates a successful irradiation. Such predictions are given on the basis of Monte Carlo calculations or a filtering approach which uses a convolution of the planned dose with specific filter functions to estimate the PET activity. In this paper, we describe and evaluate a dose reconstruction method based on PET images which reverses the just mentioned convolution approach using appropriate deconvolution methods. Deconvolution is an ill-posed inverse problem, and suitable regularization techniques are required in order to guarantee a stable solution. The basic convolution approach is developed for homogeneous media and additional procedures are necessary to generalize the PET estimation to inhomogeneous media. This generalization formalism is used in our dose deconvolution approach as well. Various simulations demonstrate that the dose reconstruction method is able to reverse the PET estimation method both in homogeneous and inhomogeneous media. Measured PET images are however degraded by noise and artifacts and the dose reconstructions become more difficult and the results suffer from artifacts as well. Recently used in-room PET scanners allow a decreased delay time between irradiation and imaging, and thus the influence of short-lived positron emitters on the PET images increases considerably. We extended our dose reconstruction method to process PET images which contain several positron emitters and simulated results are shown. PMID- 22086217 TI - Cerebral FDG-PET hypermetabolism in carcinomatous meningitis. PMID- 22086218 TI - Effects of stimulation parameters and electrode location on thresholds for epidural stimulation of cat motor cortex. AB - Epidural electrical stimulation (ECS) of the motor cortex is a developing therapy for neurological disorders. Both placement and programming of ECS systems may affect the therapeutic outcome, but the treatment parameters that will maximize therapeutic outcomes and minimize side effects are not known. We delivered ECS to the motor cortex of anesthetized cats and investigated the effects of electrode placement and stimulation parameters on thresholds for evoking motor responses in the contralateral forelimb. Thresholds were inversely related to stimulation frequency and the number of pulses per stimulus train. Thresholds were lower over the forelimb representation in motor cortex (primary site) than surrounding sites (secondary sites), and thresholds at sites <4 mm away from the primary site were significantly lower than at sites >4 mm away. Electrode location and montage influenced the effects of polarity on thresholds: monopolar anodic and cathodic thresholds were not significantly different over the primary site, cathodic thresholds were significantly lower than anodic thresholds over secondary sites and bipolar thresholds were significantly lower with the anode over the primary site than with the cathode over the primary site. A majority of bipolar thresholds were either between or equal to the respective monopolar thresholds, but several bipolar thresholds were greater than or less than the monopolar thresholds of both the anode and cathode. During bipolar stimulation, thresholds were influenced by both electric field superposition and indirect, synaptically mediated interactions. These results demonstrate the influence of stimulation parameters and electrode location during cortical stimulation, and these effects should be considered during the programming of systems for therapeutic cortical stimulation. PMID- 22086219 TI - The Cognitive Change in Women study (CCW): informant ratings of cognitive change but not self-ratings are associated with neuropsychological performance over 3 years. AB - The value of self-reported memory complaints for identifying or predicting future cognitive decline or dementia is controversial, but observations from a third party, or "informant," may prove more useful. The relationship between Informant and Self-ratings of cognitive status and neuropsychological test scores was examined in a cohort of 384 nondemented, community-dwelling women, aged 60 years and older, participating in a single-site Women's Health Initiative ancillary study. Each participant and her respective informant separately completed the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Participants also underwent neuropsychological testing and responded to questionnaires on depression and functioning in complex activities of daily living. All neuropsychological test scores were significantly correlated (P values <0.05 to <0.01) with IQCODE ratings whereas Self-ratings overestimated cognitive functioning in some domains. Furthermore, the Self and Informant ratings were both positively correlated with depression and negatively correlated with participants' activity level. Therefore, informant judgments of functional abilities are robust predictors of cognitive status in high functioning nondemented women. These results suggest that informants may be sensitive to changes that are not clinically significant but that may represent an incipient trend for decline. PMID- 22086221 TI - Acute and sublethal effects of sequential exposure to the pesticide azinphos methyl on juvenile earthworms (Eisenia andrei). AB - The use of organophosphate pesticides is an integral part of commercial farming activities and these substances have been implicated as a major source of environmental contamination and may impact on a range of non-target fauna. The extent to which soil dwelling non-target organisms are affected by exposure to the organophosphate azinphos-methyl was investigated through monitoring selected biomarker responses and life cycle effects under laboratory conditions in the earthworm Eisenia andrei. Standard acute toxicity tests were conducted followed by a sequential exposure regime experiment, in order to assess the effects of multiple pesticide applications on biomarker (cholinesterase activity and neutral red retention time), life-cycle (growth and reproduction) and behaviour (avoidance and burrowing activity) responses. The present study indicates that the time between exposure events was a more important variable than concentration and that a longer interval between exposures may mitigate the effects of pesticide exposure provided that the exposure concentration is low. Additionally, it was shown that E. andrei was unable to avoid the presence of azinphos-methyl in soil, even at concentrations as high as 50% of the LC(50) value, indicating that the presence of azinphos-methyl in the soil pose a realistic threat to earthworms and other soil dwelling organisms. The ChE inhibition test showed a high percentage inhibition of the enzyme in all exposure groups that survived and NRR times of exposed organisms were lower than that of the controls. The present study yielded important results that contribute to the understanding of biological impacts of pesticide pollution on the environment. Extrapolating these results can aid in optimising pesticide application regimes to mitigate the environmental effects thereof and thus ensuring sustained soil biodiversity in agricultural areas. PMID- 22086220 TI - Neuropsychiatric profiles in dementia. AB - We compared patterns of neuropsychiatric symptoms across 4 dementia types [Alzheimer disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB), and Parkinson disease dementia], and 2 mixed groups (AD/VAD and AD/DLB) in sample of 2,963 individuals from the National Alzheimer's Coordinating Center Uniform Data Set between September 2005 and June 2008. We used confirmatory factor analysis to compare neuropsychiatric symptom severity ratings made by collateral sources on the Neuropsychiatric Inventory Questionnaire for people with Clinical Dementia Rating scores of 1 or higher. A 3-factor model of psychiatric symptoms (mood, psychotic, and frontal) was shared across all dementia types. Between-group comparisons revealed unique neuropsychiatric profiles by dementia type. The AD group had moderate levels of mood, psychotic, and frontal symptoms whereas VAD exhibited the highest levels and Parkinson disease dementia had the lowest levels. DLB and the mixed dementias had more complex symptom profiles. Depressed mood was the dominant symptom in people with mild diagnoses. Differing psychiatric symptom profiles provide useful information regarding the noncognitive symptoms of dementia. PMID- 22086223 TI - Highly luminescent bis-diketone lanthanide complexes with triple-stranded dinuclear structure. AB - A new bis-beta-diketone, 3,3'-bis(4,4,4-trifluoro-1,3-dioxobutyl)biphenyl (BTB), has been designed and prepared for the synthesis of a series of dinuclear lanthanide complexes [Ln(2)(BTB)(3)(C(2)H(5)OH)(2)(H(2)O)(2)] [Ln = Eu (1), Gd (2)], [Ln(2)(BTB)(3)(DME)(2)] [Ln = Nd (3), Yb (4); DME = ethylene glycol dimethyl ether] and [Eu(2)(BTB)(3)(L)(2)] [L = 2,2-bipydine (5); 1,10 phenanthroline (6); 4,7-diphenyl-1,10-phenanthroline (7)]. Complexes 1-7 have been characterized by various spectroscopic techniques and their photophysical properties are investigated. X-ray crystallographical analysis reveals that complexes 1, 3 and 4 adopt triple-stranded dinuclear structures which are formed by three bis-bidentate ligands with two lanthanide ions. The complexes 1 and 3-7 display strong visible red or NIR luminescence upon irradiation at ligand band around 372 nm, depending on the choice of the lanthanide. The solid-state photoluminescence quantum yields and the lifetimes of Eu(3+) complexes are determined and described. PMID- 22086222 TI - Patellar morphology and femoral component geometry influence patellofemoral contact stress in total knee arthroplasty without patellar resurfacing. AB - PURPOSE: The objective of this study was to determine the effect of patellar morphology and implant design on patellofemoral contact stress in total knee arthroplasty (TKA) without patellar resurfacing. METHODS: Radiographic investigation: One hundred and fifty-seven knees of 127 patients were included in the study. Implants used in the present series were Low Contact Stress (LCS), Genesis II and NexGen. The relationship between the pre-operative patellar facet angle and newly identified post-operative osteosclerosis was assessed. Finite element analysis: Using patient-specific patellar three-dimensional finite element models, the relationship between the patellar facet angle and mean von Mises stress within the patella was calculated at flexion angles of 15 degrees , 45 degrees , 75 degrees and 105 degrees . RESULTS: Radiographic investigation: Post-operative osteosclerosis was observed with decreasing patellar facet angle in the Genesis II (odds ratio = 0.72; 95% confidence interval, 0.55-0.93; P = 0.012) and NexGen implants (odds ratio = 0.87; 95% confidence interval, 0.77 0.99; P = 0.029). Patients treated with the Genesis II had significantly more advanced osteosclerosis than those treated with the other two implants. Finite element analysis: A negative correlation was found between the patellar facet angle and the mean von Mises stress for all three implants. The Genesis II showed significantly higher von Mises stress than the other two implants at flexion angles of 15 degrees , 45 degrees and 105 degrees . CONCLUSIONS: Both patellar morphology and femoral component geometry influence patellofemoral contact stress in total knee arthroplasty without patellar resurfacing. LEVEL OF EVIDENCE: Case control study, Level III. PMID- 22086224 TI - Challenge of neurorehabilitation for cerebellar degenerative diseases. AB - Cerebellar Ataxia Rehabilitation trial tested if intensive rehabilitation improved ataxia, gait, and activities of daily living (ADLs) in 42 patients with degenerative cerebellar diseases. They were randomly assigned to the immediate intervention group or the delayed-entry control group. The immediate group received 1 h physical and 1 h occupational therapy for 4 weeks and delayed-entry control group received the same intervention after 4-week delay. The immediate group showed significantly greater functional gains in ataxia, gait speed, and ADLs than control. The improvements in ataxia and gait speed were sustained at 12 and 24 weeks after the intervention, respectively. Further strategies inducing meaningful gains for a longer period should be investigated. PMID- 22086226 TI - [Endocrinology and rheumatology]. PMID- 22086227 TI - [Comments by the German Society of Rheumatology (DGRh) to report on the plan for Biologicals in the second-line therapy of rheumatoid arthritis]. PMID- 22086229 TI - Can gemcitabine instillation ablate solitary low-risk non-muscle-invasive bladder cancer? Results of a phase II marker lesion study. AB - PURPOSE: The purpose of this phase II study was to evaluate whether low-risk non muscle-invasive bladder cancer can be ablated with intravesical gemcitabine in a marker lesion study. PATIENTS AND METHODS: The study had a Simon II-stage design. Thirteen patients were to be recruited for stage I. In the event of >=4 responses, another 30 patients were to be recruited. Patients were given gemcitabine 2,000 mg intravesically once per week for 6 weeks and the response was assessed with endoscopic, histological, and urine cytological findings. RESULTS: Fourteen patients evaluated for efficacy completed the study; complete responses were achieved by 2 patients (14.3%), both of these patients had lesions of <1 cm. Eleven patients (78.6%) were non-responders and 1 patient (7.1%) had progressive disease. Since the response rate in stage I was below the minimal pre defined limit, the study was stopped. CONCLUSIONS: This study shows that intravesical gemcitabine does not merit further study in this patient population. A tumor size of >1 cm may be a critical factor in accounting for the low response rate. PMID- 22086230 TI - Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor. AB - Millions of individuals are prescribed platelet inhibitors, such as aspirin and clopidogrel, to reduce their risk of thrombosis-related clinical events. Unfortunately many platelet inhibitors are contraindicated in surgical settings because of their inherent bleeding risk complicating the treatment of patients who require surgery. We describe the development of a potent antiplatelet agent, an RNA aptamer-termed Ch-9.14-T10 that binds von Willebrand factor (VWF) with high affinity and inhibits thrombosis in a murine carotid artery damage model. As expected, when this potent antiplatelet agent is administered, it greatly increases bleeding from animals that are surgically challenged. To improve this antiplatelet agent's safety profile, we describe the generation of antidotes that can rapidly reverse the activity of Ch-9.14-T10 and limit blood loss from surgically challenged animals. Our work represents the first antidote controllable antiplatelet agent, which could conceivably lead to improved medical management of patients requiring antiplatelet medication who also need surgery. PMID- 22086231 TI - An artificial PAP gene breaks self-tolerance and promotes tumor regression in the TRAMP model for prostate carcinoma. AB - Prostate cancer (PCa) is the most commonly diagnosed type of cancer in men in western industrialized countries. As a public health burden, the need for the invention of new cost-saving PCa immunotherapies is apparent. In this study, we present a DNA vaccine encoding for the prostate-specific antigen prostatic acid phosphatase (PAP) linked to the J-domain and the SV40 enhancer sequence. The PAP DNA vaccine induced a strong PAP-specific cellular immune response after electroporation (EP)-based delivery in C57BL/6 mice. Splenocytes from mice immunized with PAP recognized the naturally processed PAP epitopes, indicating that vaccination with the PAP-J gene broke its self-tolerance against PAP. Remarkably, DNA vaccination with PAP-J inhibited tumor growth in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model that closely resembled human PCa. Therefore, this study highlights a novel cancer immunotherapy approach with the potential to control PCa in clinical settings. PMID- 22086232 TI - Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy. AB - We previously conducted a proof of principle; dose escalation study in Duchenne muscular dystrophy (DMD) patients using the morpholino splice-switching oligonucleotide AVI-4658 (eteplirsen) that induces skipping of dystrophin exon 51 in patients with relevant deletions, restores the open reading frame and induces dystrophin protein expression after intramuscular (i.m.) injection. We now show that this dystrophin expression was accompanied by an elevated expression of alpha-sarcoglycan, beta-dystroglycan (BDG) and--in relevant cases--neuronal nitric oxide synthase (nNOS) at the sarcolemma, each of which is a component of a different subcomplex of the dystrophin-associated glycoprotein complex (DAPC). As expected, nNOS expression was relocalized to the sarcolemma in Duchenne patients in whom the dystrophin deletion left the nNOS-binding domain (exons 42-45) intact, whereas this did not occur in patients with deletions that involved this domain. Our results indicate that the novel internally deleted and shorter dystrophin induced by skipping exon 51 in patients with amenable deletions, can also restore the dystrophin-associated complex, further suggesting preserved functionality of the newly translated dystrophin. PMID- 22086233 TI - In vivo delivery of cytoplasmic RNA virus-derived miRNAs. AB - The discovery of microRNAs (miRNAs) revealed an unappreciated level of post transcriptional control used by the cell to maintain optimal protein levels. This process has represented an attractive strategy for therapeutics that is currently limited by in vivo delivery constraints. Here, we describe the generation of a single-stranded, cytoplasmic virus of negative polarity capable of producing functional miRNAs. Cytoplasmic RNA virus-derived miRNAs accumulated to high levels in vitro, generated significant amounts of miRNA star strand, associated with the RNA-induced silencing complex (RISC), and conferred post transcriptional gene silencing in a sequence-specific manner. Furthermore, we demonstrate that these vectors could deliver miRNAs to a wide range of tissues, and sustain prolonged expression capable of achieving measurable knockdown of physiological targets in vivo. Taken together, these results validate noncanonical processing of cytoplasmic-derived miRNAs and provide a novel platform for small RNA delivery. PMID- 22086234 TI - Modification of the early gene enhancer-promoter improves the oncolytic potency of adenovirus 11. AB - Oncolytic adenoviruses based on serotype 5 (Ad5) have several shortcomings, including the downregulation of its receptor in cancer cells, high prevalence of neutralizing antibodies and hepatotoxicity. Another adenoviral serotype, Ad11, could overcome these obstacles. Here, we show that human cancer cell lines express higher levels of the Ad11 receptor CD46, resulting in much better infectivity than Ad5. Surprisingly, only 36% (9/25) of the cell lines were more sensitive to Ad11- than to Ad5-mediated cytotoxicity. Investigations revealed that it was the transcription of Ad11 E1A, not CD46 expression or virus infectivity, which determined the cell's sensitivity to Ad11 killing. Ad11 E1A mRNA levels have an effect on viral DNA replication, structural protein synthesis and infectious particle production. To test the hypothesis that increased E1A transcription would lead to improved Ad11 replication in Ad5-sensitive (but Ad11 less sensitive) cells, two Ad11 mutants (Ad11-Ad5-P and Ad11-Ad5-EP) were constructed where either the E1A promoter or enhancer-promoter, respectively, was replaced by that of Ad5. Ad11-Ad5-EP demonstrated increased E1A mRNA levels and replication, together with enhanced oncolytic potency in vitro and in vivo. This effect was found in both the Ad5-sensitive and Ad11-sensitive cancer cells, broadening the range of tumors that could be effectively killed by Ad11-Ad5-EP. PMID- 22086235 TI - Efficient gene therapy for Parkinson's disease using astrocytes as hosts for localized neurotrophic factor delivery. AB - Current gene therapy approaches for Parkinson's disease (PD) deliver neurotrophic factors like glial cell line-derived neurotrophic factor (GDNF) or neurturin via neuronal transgene expression. Since these potent signaling-inducing neurotrophic factors can be distributed through long-distance neuronal projections to unaffected brain sites, this mode of delivery may eventually cause side effects. To explore a localized and thus potentially safer alternative for gene therapy of PD, we expressed GDNF exclusively in astrocytes and evaluated the efficacy of this approach in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rat 6-hydroxy-dopamine (6-OHDA) models of PD. In terms of protection of dopaminergic cell bodies and projections, dopamine (DA) synthesis and behaviour, astrocyte-derived GDNF demonstrated the same efficacy as neuron-derived GDNF. In terms of safety, unilateral striatal GDNF expression in astrocytes did not result in delivery of bio-active GDNF to the contralateral hemispheres (potential off target sites) as happened when GDNF was expressed in neurons. Thus, astrocytic GDNF expression represents a localized but efficient alternative to current gene therapeutic strategies for the treatment of PD, especially if viral vectors with enhanced tissue penetration are considered. Astrocytic neurotrophic factor expression may open new venues for neurotrophic factor-based gene therapy targeting severe diseases of the brain. PMID- 22086236 TI - Reduced ultraviolet-induced DNA damage and apoptosis in human skin with topical application of a photolyase-containing DNA repair enzyme cream: clues to skin cancer prevention. AB - The exposure of human skin to ultraviolet radiation (UVR) results in the formation of DNA photolesions that give rise to photoaging, mutations, cell death and the onset of carcinogenic events. Photolyase (EC 4.1.99.3) is a DNA repair enzyme that reverses damage caused by exposure to UVR. We sought to investigate whether addition of photolyase enhances the protection provided by a traditional sunscreen (SS), by reducing the in vivo formation of cyclobutane-type pyrimidine dimers (CPDs) and UVR-induced apoptosis in human skin. Ten volunteers (Fitzpatrick skin type II) were exposed to solar-simulated (ss) UVR at a three times minimal erythema dose for 4 consecutive days. Thirty minutes prior to each exposure, the test materials [vehicle, SS (sun protection factor 50) alone, and SS plus photolyase from Anacystis nidulans] were applied topically to three different sites. One additional site was left untreated and one received ssUVR only. Biopsy specimens were taken 72 h after the last irradiation. The amount of CPDs and the extent of apoptosis were measured by ELISA. Photolyase plus SS was superior to SS alone in reducing both the formation of CPDs and apoptotic cell death (both P<0.001). In conclusion, the addition of photolyase to a traditional SS contributes significantly to the prevention of UVR-induced DNA damage and apoptosis when applied topically to human skin. PMID- 22086237 TI - siRNA directed against Livin inhibits tumor growth and induces apoptosis in human glioma cells. AB - Livin, a novel member of the human inhibitors of apoptosis protein family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. The present study was designed to investigate the potential of using RNA interference (RNAi) technique to downregulate Livin expression, and the subsequent effect on human glioma cells. The results showed that knockdown of Livin expression by short interfering RNA (siRNA) significantly inhibited glioma cell proliferation and increased cell apoptosis through cell arrest in the G(1)/G(0) phase of cell cycle in vitro. Furthermore, Livin siRNA significantly suppressed tumor growth in nude mice. Together, these findings suggest that RNAi-mediated downregulation of Livin expression could lead to potent antitumor activity in glioma cells and might serve as a novel therapeutic strategy in clinic. PMID- 22086240 TI - Traditional versus non-traditional nest-site choice: alternative decision strategies for nest-site selection. AB - In order to understand habitat selection, it is important to consider the way individual animals assess the suitability of a future reproductive site. One way of investigating mechanisms (such as those involved in nest site selection) is to examine breeding success and habitat characteristics in terms of animals returning to a place where they have already reproduced and using the same location over successive years or searching for new alternatives. This approach seems especially suitable for testing recent hypotheses suggesting that nest site selection is an integrative process that includes the use of social information (e.g. past breeding success of conspecifics). Determining the factors that elicit conservative or innovative behaviour regarding nest-site selection could be important for improving our understanding of habitat selection decisions in animals. More than half of the nests of the long-distance migratory lesser grey shrike Lanius minor, are built in the same or neighbouring trees. We found no evidence that habitat characteristics influence nest-site tradition. On the contrary, social information in terms of the presence of conspecifics and past reproductive success in terms of complete nest failures due to nest predation (but not detailed information such as variation in fledgling number) influenced nest-site tradition. Hence, social information and past reproductive success may play a role in nest-site choice in this species. Our results further demonstrate that previous experience with a nest site does not appear to be beneficial. PMID- 22086238 TI - The role of stereotactic radiosurgery in cavernous sinus hemangiomas: a systematic review and meta-analysis. AB - Cavernous sinus hemangioma is a rare and complex vascular tumor. A direct microsurgical approach usually results in massive hemorrhage. Stereotactic radiosurgery has emerged as a treatment alternative to microsurgery. To conduct a meta-analysis assessing the effect and complications of stereotactic radiosurgery in cavernous sinus hemangioma, a systematic review and meta-analysis of all cases of cavernous hemangioma in the cavernous sinus treated with stereotactic radiosurgery was performed. The search revealed ten papers with a total enrollment of 59 patients. Tumor size ranged from 1.5-51.4 cm(3) (mean 9.6 cm(3)). The mean follow-up period was 49.2 months (range 6-156 months). The most recent MR images demonstrated remarkable tumor shrinkage in 40 patients (67.8%), partial shrinkage in 15 patients (25.4%), and no change in four patients (6.8%). There was no significant correlation between lesion volume and tumor shrinkage. Patients with remarkable tumor shrinkage received higher doses than those with partial or no change tumor shrinkage (P = 0.031). Thirteen patients (22.0%) had no cranial nerve impairments before stereotactic radiosurgery. Among those 46 patients with cranial nerve impairments before stereotactic radiosurgery, complete resolution was achieved in seven patients and improvement in 28, and these impairments remained essentially unchanged in 11 patients. Only one patient had additional trigeminal nerve disturbance. There is no statistical significance in tumor control between patients treated with or without surgery (P = 0.091). The meta-analysis suggests stereotactic radiosurgery avoids the complications associated with attempted microsurgical resection. Stereotactic radiosurgery is an alternative for cavernous sinus hemangiomas confirmed by typical imaging. PMID- 22086239 TI - Complete regression of papillary tumor of the pineal region after radiation therapy: case report and review of the literature. AB - Papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor that arises in the pineal region. The optimal treatment for PTPR remains controversial, as no definitive treatment strategy exists for this lesion. It is not clear whether aggressive surgical removal is superior to biopsy followed by radiotherapy. The majority of cases in the literature have undergone attempted gross total resection with a supracerebellar-infratentorial or a transcallosal transventricular approach. In this report, we describe a case of PTPR in a 23 year-old male that presented as a third ventricular mass causing obstructive hydrocephalus. An endoscopic third ventriculostomy was performed followed by an endoscopic biopsy. Postoperative radiotherapy resulted in complete regression of the tumor with no evidence of tumor recurrence at 25 months. This case highlights a minimally invasive strategy for a rare neoplasm that resulted in a favorable response to radiation therapy, thereby avoiding the risks of aggressive surgical removal. We also review the radiographic and histopathologic features of PTPR and discuss various options of treatment reported in the literature. PMID- 22086241 TI - Abstracts of the 11th European Nutrition Conference (FENS). Madrid, Spain. October 26-29, 2011. PMID- 22086242 TI - Characterization of an extendable multi-leaf collimator for clinical electron beams. AB - An extendable x-ray multi-leaf collimator (eMLC) is investigated for collimation of electron beams on a linear accelerator. The conventional method of collimation using an electron applicator is impractical for conformal, modulated and mixed beam therapy techniques. An eMLC would allow faster, more complex treatments with potential for reduction in dose to organs-at-risk and critical structures. The add-on eMLC was modelled using the EGSnrc Monte Carlo code and validated against dose measurements at 6-21 MeV with the eMLC mounted on a Siemens Oncor linear accelerator at 71.6 and 81.6 cm source-to-collimator distances. Measurements and simulations at 8.4-18.4 cm airgaps showed agreement of 2%/2 mm. The eMLC dose profiles and percentage depth dose curves were compared with standard electron applicator parameters. The primary differences were a wider penumbra and up to 4.2% reduction in the build-up dose at 0.5 cm depth, with dose normalized on the central axis. At 90 cm source-to-surface distance (SSD)--relevant to isocentric delivery--the applicator and eMLC penumbrae agreed to 0.3 cm. The eMLC leaves, which were 7 cm thick, contributed up to 6.3% scattered electron dose at the depth of maximum dose for a 10 * 10 cm2 field, with the thick leaves effectively eliminating bremsstrahlung leakage. A Monte Carlo calculated wedge shaped dose distribution generated with all six beam energies matched across the maximum available eMLC field width demonstrated a therapeutic (80% of maximum dose) depth range of 2.1-6.8 cm. Field matching was particularly challenging at lower beam energies (6-12 MeV) due to the wider penumbrae and angular distribution of electron scattering. An eMLC isocentric electron breast boost was planned and compared with the conventional applicator fixed SSD plan, showing similar target coverage and dose to critical structures. The mean dose to the target differed by less than 2%. The low bremsstrahlung dose from the 7 cm thick MLC leaves had the added advantage of reducing the mean dose to the whole heart. Isocentric delivery using an extendable eMLC means that treatment room re-entry and repositioning the patient for SSD set-up is unnecessary. Monte Carlo simulation can accurately calculate the fluence below the eMLC and subsequent patient dose distributions. The eMLC generates similar dose distributions to the standard electron applicator but provides a practical method for more complex electron beam delivery. PMID- 22086243 TI - Shape-based classification of 3D facial data to support 22q11.2DS craniofacial research. AB - 3D imaging systems are used to construct high-resolution meshes of patient's heads that can be analyzed by computer algorithms. Our work starts with such 3D head meshes and produces both global and local descriptors of 3D shape. Since these descriptors are numeric feature vectors, they can be used in both classification and quantification of various different abnormalities. In this paper, we define these descriptors, describe our methodology for constructing them from 3D head meshes, and show through a set of classification experiments involving cases and controls for a genetic disorder called 22q11.2 deletion syndrome that they are suitable for use in craniofacial research studies. The main contributions of this work include: automatic generation of novel global and local data representations, robust automatic placement of anthropometric landmarks, generation of local descriptors for nasal and oral facial features from landmarks, use of local descriptors for predicting various local facial features, and use of global features for 22q11.2DS classification, showing their potential use as descriptors in craniofacial research. PMID- 22086244 TI - Dietary nitrate - a slow train coming. PMID- 22086245 TI - Monoacylglycerol lipase: stopping surplus at the synapse. PMID- 22086246 TI - PLC: Johnny-come-lately to ORAI and the ups and downs of calcium signalling. PMID- 22086247 TI - Elevated haematocrit - when too much of a good thing wreaks havoc on the endothelial surface layer. PMID- 22086248 TI - Caveat utilitor: take measure of your marker. PMID- 22086249 TI - Loss of brainstem serotonergic neurons impairs autoresuscitation in neonate rats: is this relevant to the sudden infant death syndrome? PMID- 22086250 TI - Sex specific association of potassium channel subunits. PMID- 22086251 TI - An 'exciting' spin on cannabinoid signalling. PMID- 22086252 TI - Dimethyl sulphoxide addition or withdrawal causes biphasic volume changes and its withdrawal causes t-system vacuolation in skeletal muscle. PMID- 22086254 TI - Dynamics of intracranial venous flow patterns in patients with idiopathic intracranial hypertension. AB - OBJECTIVE: To examine the dynamics of intracranial venous flow patterns in patients with idiopathic intracranial hypertension (IIH). METHODS: Nonrandomized controlled trial analyzing the difference in cerebral perfusion in 13 IIH patients and 12 healthy controls using contrast-enhanced duplex sonography. In patients, an additional 3D gradient echo magnetic resonance venography (MRV) using a new technique was performed to quantify stenosis of the cerebral sinus. The cerebral perfusion parameters, including cerebral transit time (CTT) and time to peak (TTP), were analyzed. RESULTS: IIH patients had a higher BMI (29.3 [95% CI 26.4, 32.2] vs. 23.3 [95% CI 20.7, 25.9], p = 0.003) and an increased prevalence of headache, but all other clinical characteristics were comparable. The CTT did not differ significantly. The TTP was significantly longer in IIH patients compared to controls (8.5 [95% CI 7.6, 9.4] vs. 7.3 s [95% CI 6.3, 8.1], p = 0.04). Twelve of 13 (92%) IIH patients showed stenosis of the cerebral sinus. CONCLUSIONS: Our study is the first to report an altered cerebral venous flow in IIH patients compared to controls using a dynamic ultrasonographic technique. A simplified MRV technique confirms the high prevalence and reliable detection of venous stenosis in IIH patients. PMID- 22086255 TI - Influence of preoperative chemotherapy on the intraoperative and postoperative course of liver resection for colorectal cancer metastases. AB - BACKGROUND: Liver resection is a possibly curative treatment for colorectal cancer (CRC) liver metastases. Preoperative chemotherapy may make initially irresectable tumors resectable. The aim of this study was to compare perioperative course and short-term mortality after liver resection for CRC metastases between patients who were and were not treated with preoperative chemotherapy. METHODS: Patients who had undergone liver resection for CRC metastases were included. A total of 97 patients treated with preoperative chemotherapy (group A) were compared with 136 who were not (group B). Intraoperative bleeding, operating time, complications, duration of stay, and mortality were compared using Pearson's chi(2) test, Fisher's exact test, and the Mann-Whitney U-test. RESULTS: Mean intraoperative bleeding, duration of stay, and operating time were not significantly different. Complications occurred in 62.9% and 63.2% in groups A and B, respectively. The 30- and 90-day mortality rates were zero in group A, comparable to 1.5% in group B. CONCLUSIONS: There were no significant differences in the perioperative course or postoperative mortality when comparing CRC patients with or without chemotherapy prior to liver resection. Consequently, this study suggests that preoperative chemotherapy before liver resection for CRC metastases does not negatively influence perioperative outcome and can therefore be applied if "downstaging" is indicated. PMID- 22086256 TI - Primary closure following laparoscopic common bile duct exploration combined with intraoperative cholangiography and choledochoscopy. AB - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) has become one of the main options for treating choledocholithiasis associated with cholelithiasis. Our objective was to assess the short-term outcomes of patients undergoing laparoscopic primary closure of the common bile duct (CBD) compared with laparoscopic choledochotomy plus T-tube drainage. METHODS: We retrospectively studied 137 patients undergoing primary closure following LCBDE (group A) compared with 102 cases with laparoscopic choledochotomy plus T-tube drainage (group B) between January 2007 and January 2010. Intraoperative cholangiography (IOC) and choledochoscopy were performed in all patients. RESULTS: Three patients in group A (2.2%) were converted to open surgery and two (2.0%) in group B because of serious adherence. According to routine IOC, unexpected CBD stones were found in 16 cases (6.8%). The duration of the operation in group A was shorter than in group B (92.4 +/- 15.2 vs. 125.7+/- 32.6 min, P < 0.05), as was length of postoperative stay (3.1+/- 2.4 vs. 5.7+/- 4.3 days, P < 0.05). Postoperative bile leakage occurred in six patients (4.5%) in group A and four cases (4.0%) in group B; all of the patients recovered after simple drainage without reoperation. Bile peritonitis was seen in one case after T-tube removal. The median follow-up was 26 months. There were no recurrences. CONCLUSIONS: Laparoscopic primary closure of the CBD is safe and successful for the management of CBD stones. Application of IOC and choledochoscopy to ensure clearance of the CBD and careful suturing are essential for primary closure. PMID- 22086258 TI - Direct and inverse reactions of LiH+ with He(1S) from quantum calculations: mechanisms and rates. AB - The gas-phase reaction of LiH(+) (X(2)Sigma) with He((1)S) atoms, yielding Li(+)He with a small endothermicity for the rotovibrational ground state of the reagents, is analysed using the quantum reactive approach that employs the Negative Imaginary Potential (NIP) scheme discussed earlier in the literature. The dependence of low-T rates on the initial vibrational state of LiH(+) is analysed and the role of low-energy Feshbach resonances is also discussed. The inverse destruction reaction of LiHe(+), a markedly exothermic process, is also investigated and the rates are computed in the same range of temperatures. The possible roles of these reactions in early universe astrophysical networks, in He droplets environments or in cold traps are briefly discussed. PMID- 22086257 TI - A finite element analysis of the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in tDCS. AB - We investigated the effect of electrode area and inter-electrode distance on the spatial distribution of the current density in transcranial direct current stimulation (tDCS). For this purpose, we used the finite element method to compute the distribution of the current density in a four-layered spherical head model using various electrode montages, corresponding to a range of electrode sizes and inter-electrode distances. We found that smaller electrodes required slightly less current to achieve a constant value of the current density at a reference point on the brain surface located directly under the electrode center. Under these conditions, smaller electrodes also produced a more focal current density distribution in the brain, i.e. the magnitude of the current density fell more rapidly with distance from the reference point. The combination of two electrodes with different areas produced an asymmetric current distribution that could lead to more effective and localized neural modulation under the smaller electrode than under the larger one. Focality improved rapidly with decreasing electrode size when the larger electrode sizes were considered but the improvement was less marked for the smaller electrode sizes. Also, focality was not affected significantly by inter-electrode distance unless two large electrodes were placed close together. Increasing the inter-electrode distance resulted in decreased shunting of the current through the scalp and the cerebrospinal fluid, and decreasing electrode area resulted in increased current density on the scalp under the edges of the electrode. Our calculations suggest that when working with conventional electrodes (25-35 cm(2)), one of the electrodes should be placed just 'behind' the target relative to the other electrode, for maximum current density on the target. Also electrodes with areas in the range 3.5-12 cm(2) may provide a better compromise between focality and current density in the scalp than the traditional electrodes. Finally, the use of multiple small return electrodes may be more efficient than the use of a single large return electrode. PMID- 22086259 TI - Transvaginal placement of surgical mesh for pelvic organ prolapse: more FDA concerns--positive reactions are possible. PMID- 22086260 TI - Time to rethink: an evidence-based response from pelvic surgeons to the FDA Safety Communication: "UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse". AB - In July of 2011 the U.S. Food and Drug Administration (FDA) released a safety communication entitled "UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse." The stated purpose of this communication is to inform health care providers and patients that serious complications with placement of this mesh are not rare and that it is not clear that these repairs are more effective than nonmesh repair. The comments regarding efficacy are based on a systematic review of the scientific literature from 1996-2011 conducted by the FDA. Our review of the literature during this time yields some different conclusions regarding the safety and efficacy of mesh use in prolapse repair. It may be useful to consider this information prior to making recommendations regarding mesh use in prolapse surgery according to the recent UPDATE. PMID- 22086261 TI - A perfect storm. PMID- 22086262 TI - The mesh debate. PMID- 22086263 TI - Does a ring pessary in situ influence the pelvic floor muscle function of women with pelvic organ prolapse when tested in supine? AB - INTRODUCTION AND HYPOTHESIS: It has been suggested that repositioning pelvic organ prolapse (POP) by pessary support may improve pelvic floor muscle (PFM) function. The aim of the present study was to compare vaginal resting pressure and maximal voluntary contraction (MVC) of the PFM measured with and without a ring pessary in situ. METHODS: This was a short-term experimental study with women acting as their own controls. Twenty-two women with POP quantified II-IV were included. Vaginal resting pressure and MVC was measured with a manometer (Camtech AS) in supine position. Difference between measurements with and without the ring pessary was analyzed by paired sample t test and Wilcoxon signed rank test. Significance level was <0.05. RESULTS: There was a statistically significant difference in measurement of vaginal resting pressure (p <0.01) but not of MVC (p= <0.68) with the ring pessary in situ. CONCLUSIONS: Measurement of PFM strength can be done without repositioning the prolapse. PMID- 22086264 TI - Laparoscopic sacrocolpopexy with bone anchor fixation: short-term anatomic and functional results. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate short-term anatomic and functional outcomes and safety of laparoscopic sacrocolpopexy with bone anchor fixation. METHODS: A prospective cohort study of women undergoing laparoscopic sacrocolpopexy between 2004 and 2009. Anatomic outcome was assessed using the pelvic organ prolapse quantification score (POP-Q). Functional outcomes were assessed using the Urogenital Distress Inventory, Defecatory Distress Inventory, and the Incontinence Impact Questionnaire preoperatively and at 6 months postoperatively. The Wilcoxon signed rank test was used to test differences between related samples. RESULTS: Forty-nine women underwent laparoscopic sacrocolpopexy. The objective success rate in the apical compartment was 98%, subjective success rate was 79%. One mesh exposure (2%) was found. One conversion was necessary due to injury to the ileum. CONCLUSIONS: Laparoscopic sacrocolpopexy with bone anchor fixation is a safe and efficacious treatment for apical compartment prolapse. It provides excellent apical support and good functional outcome 6 months postoperatively. PMID- 22086265 TI - Comparison of the cough stress test and 24-h pad test in the assessment of stress urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: The 24-h pad test and cough stress test are commonly used to assess stress urinary incontinence; however, no comparative data are available. The cough stress test is superior to the 24-h pad test. METHODS: Women with predominant stress urinary incontinence symptoms underwent a cough stress test, a 24-h pad test, and urodynamic testing. RESULTS: Complete data were available on 55 women. Agreement between the urodynamic results and the stress test occurred in 89% of women (k = 0.51). Sensitivity, specificity, and positive and negative predictive values were 90%, 80%, 98%, and 44%. Agreement between the urodynamic results and the pad test occurred in 60% of women (k = 0.08). Sensitivity, specificity, and positive and negative predictive values were 60%, 60%, 94%, and 13%. Agreement between the cough stress test and the pad test occurred in 67% (k = 0.26). CONCLUSIONS: The cough stress test is more reliable than the pad test for documentation of stress urinary incontinence. PMID- 22086266 TI - Indoor air quality assessment in child care and medical facilities in Korea. AB - In order to characterize the status of indoor air pollution in some important facilities, a list of key criteria pollutants [particulate matter (PM(10)), carbon dioxide (CO(2)), carbon monoxide (CO), formaldehyde (HCHO), and bioaerosol] was measured from a total of 91 randomly selected sites in 18 different cities, Korea (February 2006 to December 2009). The target facilities include 43 child care facilities, 38 medical facilities, 6 elementary schools, and 4 postnatal care centers. The results showed that some air pollutants (e.g., CO and HCHO) did not exceed the recommended guideline [e.g., the Korean indoor air standard (KIAS) values of 10 ppm and 100 ppb, respectively]. However, concentration of PM(10), CO(2), and bioaerosol occasionally exceeded their respective guidelines (e.g., seven, three, and two cases). Discrete seasonalities were observed from indoor pollutants because of varying ventilation practice (e.g., summer time dominance of PM(10), HCHO, and bioaerosol or winter dominance of CO(2) and CO). However, as the concentrations of the indoor pollutants were scarcely above the recommended guideline level, more diversified approaches are desirable to diagnose the status of indoor pollution and to provide a realistic strategy for the improvement of IAQ. PMID- 22086268 TI - Abstracts of the 4th World Congress on Women's Mental Health, hosted by the International Association for Women's Mental Health. March 16-19, 2011. Madrid, Spain. PMID- 22086267 TI - Tidally driven N, P, Fe and Mn exchanges in salt marsh sediments of Tagus estuary (SW Europe). AB - Short-sediment cores and flooding water were collected at 0, 5, 15, 25 and 50 min of tidal inundation in the two sites colonised by pure stands of Spartina maritima (low marsh) and Sarcocornia fruticosa (high marsh) from the Rosario salt marsh (Tagus estuary, SW Europe). Concentrations of NH(4)(+), NO(3)(-) + NO(2)(-) and HPO (4)(2-), Fe and Mn were measured in tidal flooding water and pore water. Flooding water is enriched in nutrients, particularly ammonium due to local discharge of untreated urban effluents. Nevertheless, NH(4)(+) and NO(3)(-) + NO(2)(-) concentrations in flooding waters at t = 5 min (NH(4)(+) = 246 +/- 7 MUM, NO(3)(-) + NO(2)(-) = 138 +/- 1 MUM for S. fruticosa and NH(4)(+) = 256 +/- 8 MUM, NO(3)(-) + NO(2)(-) = 138 +/- 1 MUM for S. maritima) rose sharply at both vegetated sites. An increase was also registered for HPO(4)(2-) and total dissolved Fe although the subsequent decrease was smoother. Advective transport induced by the two daily pulses of inundation is several orders of magnitude higher than the diffusive fluxes during submerged periods. In addition, solutes are exported from the sediment with the inundation and imported in submerged periods. The exported amount of inorganic nitrogen during tidal inundation (export of 3,200 MUmol N m(-2) day(-1)to the water column), is not counterbalanced by the sink of -290 MUmol N m(-2) day(-1) occurred during the submerged period. PMID- 22086270 TI - Fetoscopic laser photocoagulation of feeding vessels to a large placental chorioangioma following fetal deterioration after amnioreduction. AB - Large placental chorioangiomas (>4 cm) can precipitate severe polyhydramnios, fetal anemia, growth restriction, high-output cardiac failure, hydrops, and fetal demise. We report a case of a large chorioangioma that was treated in a stepwise fashion with amnioreduction to ameliorate maternal discomfort, followed by fetoscopic laser ablation of the feeding vessels after rapid evolution of heart failure. Although amnioreduction was helpful in improving maternal symptoms, we suspect that the drop in intrauterine pressure from the amniotic fluid decompression may have resulted in increased tumor perfusion, thereby promoting fetal deterioration due to a 'steal' phenomenon. Close scrutiny of the fetal status via ultrasound is required, particularly if amnioreduction is necessary, and definitive treatment should be considered once early signs of heart failure develop. Fetoscopic laser ablation of the feeding vessels is a feasible definitive treatment of a large chorioangioma in cases in which perfusion of the tumor is via a superficial nonterminus umbilical artery. Future reports should describe the anatomy of the blood supply to the chorioangioma, in the hopes that further guidelines for surgical candidacy may be established. PMID- 22086271 TI - LY294002 enhances cytotoxicity of temozolomide in glioma by down-regulation of the PI3K/Akt pathway. AB - The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas. However, a considerable number of glioblastoma (GBM) cases are refractory to TMZ. Previous studies have revealed that the PI3K/Akt pathway is activated in an ataxia telangiectasia and Rad3 related-dependent manner in response to TMZ. Thus, we hypothesized that PI3K inhibitors may act as antitumor agents against gliomas and potentiate the cytotoxicity of TMZ. The cytotoxicity of a PI3K inhibitor, LY294002, was examined both alone and in combination with TMZ in human glioma cell lines. Proliferation of tumor cells treated with LY294002 in combination with TMZ was significantly suppressed compared to treatment with either drug used alone. The combination treatment induced a higher apoptosis rate, while reducing the invasive capability of U87 cells. The apoptosis-associated proteins, cleaved-caspase-3 and Bax, were more significantly up-regulated by the combined treatment than by TMZ used alone. In addition, p-Akt and Bcl-2, which can promote TMZ resistance, were markedly decreased by LY294002. These findings suggest that LY294002 enhances the cytotoxicity of TMZ by down regulation of the PI3K/Akt pathway. PMID- 22086272 TI - Advanced therapy for pulmonary arterial hypertension due to congenital heart disease: a clinical perspective in a new therapeutic era. PMID- 22086273 TI - Polymer imprinting with iron-oxo-hydroxo clusters: [Fe6O2(OH)2(O2CC(Cl)=CH2)12(H2O)2], [Fe6O2(OH)2(O2C-Ph-(CH)=CH2)12(H2O)2] and [{Fe(O2CC(Cl)=CH2)(OMe)2}10]. AB - We report the syntheses of imprinted polymers using iron-oxo-hydroxo clusters as templates. Three new iron clusters, [Fe(6)O(2)(OH)(2)(O(2)CC(Cl)=CH(2))(12)(H(2)O)(2)] (1), [{Fe(O(2)CC(Cl)=CH(2))(OMe)(2)}(10)] (2) and [Fe(6)O(2)(OH)(2)(O(2)C-Ph (CH)=CH(2))(12)(H(2)O)(2)] (3) have been prepared from commercially-available carboxylic acids. Cluster-imprinted-polymers (CIPs) of 1, 2 and 3 were prepared with ethylene glycol dimethacrylate monomer, and of 1 with methyl methacrylate monomer. The imprinted sites within the CIPs were examined using EXAFS and diffuse reflectance UV/vis spectroscopy, demonstrating that the clusters 1, 2 and 3 were incorporated intact within the polymers. Extraction of the clusters from the CIPs imprinted with 1 and 3 gave new polymers that showed evidence of an imprinting effect. PMID- 22086274 TI - Celebrating synthesis. PMID- 22086284 TI - Protein structure: Charting a new course in coiled coils. PMID- 22086285 TI - Signaling pathways: Purinosomes under GPCR control. PMID- 22086286 TI - Protein misfolding: Tracking a toxic polyQ epitope. PMID- 22086287 TI - Membrane trafficking: Arls squeeze the fat out. PMID- 22086288 TI - Lessons and revelations from biomimetic syntheses. AB - Biomimetic synthesis describes the field of organic chemistry that aims to emulate the natural, biosynthetic processes toward natural products. As well as providing insight into how molecules are formed in nature, the benefits of this approach to total synthesis are numerous and extend beyond the gains typical of traditional synthesis. For example, using biosynthetic proposals to design a synthetic route can highlight alternative methods to the desired target. The pursuit of biomimetic syntheses also promotes the development of new reactions to prove or disprove a biosynthetic proposal or to unravel mechanistic implications of a proposed biosynthesis and can lead to the identification of new natural products. Here we look at some recent compelling examples and examine how biomimetic synthesis has led to the discovery of new procedures and principles that would not have been found by other approaches. PMID- 22086290 TI - Pretreatment of rapeseed straw by sodium hydroxide. AB - Pretreatment method for rapeseed straw by sodium hydroxide was investigated for production of bioethanol and biobutanol. Various pretreatment parameters, including temperature, time, and sodium hydroxide concentration were optimized using a statistical method which is a central composite design of response surface methodology. In the case of sodium hydroxide pretreatment, optimal pretreatment conditions were found to be 7.9% sodium hydroxide concentration, 5.5 h of reaction time, and 68.4 degrees C of reaction temperature. The maximum glucose yield which can be recovered by enzymatic hydrolysis at the optimum conditions was 95.7% and the experimental result was 94.0 +/- 4.8%. This experimental result was in agreement with the model prediction. An increase of surface area and pore size in pretreated rapeseed straw by sodium hydroxide pretreatment was observed by scanning electron microscope. PMID- 22086289 TI - Choosing an effective protein bioconjugation strategy. AB - The collection of chemical techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be addressed, leading to advances in biological understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate production, and a number of techniques can be used to label a single protein in a complex biological mixture. This review examines the way in which experimental circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts. PMID- 22086291 TI - The conserved bauplan of the teleostean telencephalon. PMID- 22086292 TI - Body integrity identity disorder: deranged body processing, right fronto-parietal dysfunction, and phenomenological experience of body incongruity. AB - Body integrity identity disorder (BIID) is characterised by profound experience of incongruity between the biological and desired body structure. The condition manifests in "non-belonging" of body parts, and the subsequent desire to amputate, paralyse or disable a limb. Little is known about BIID; however, a neuropsychological model implicating right fronto-parietal and insular networks is emerging, with potential disruption to body representation. We argue that, as there is scant systematic research on BIID published to date and much of the research is methodologically weak, it is premature to assume that the only process underlying bodily experience that is compromised is body representation. The present review systematically investigates which aspects of neurological processing of the body, and sense of self, may be compromised in BIID. We argue that the disorder most likely reflects dysregulation in multiple levels of body processing. That is, the disunity between self and the body could arguably come about through congenital and/or developmental disruption of body representations, which, together with altered multisensory integration, may preclude the experience of self-attribution and embodiment of affected body parts. Ulimately, there is a need for official diagnostic criteria to facilitate epidemiological characterisation of BIID, and for further research to systematically investigate which aspects of body representation and processing are truly compromised in the disorder. PMID- 22086294 TI - Genomic analysis of a four-way t(4;11;22;10) associated with MLL-AF4 in an adult acute lymphoblastic leukemia. PMID- 22086295 TI - Role of HuR in keratinocyte migration and wound healing. AB - Human antigen R (HuR) is a post-translational modifier of mRNAs rich in AU- and U rich elements. These mRNAs typically code for proteins involved in cell growth and differentiation, signal transduction, transcriptional and translational control, apoptosis, nutrient transport and metabolism. Thus, HuR affects a variety of biological functions and processes. Via its effect on growth and cellular migration, HuR has been shown to enhance clinical progression of a number of cancers. Its role in wound healing remains unknown. In the present study, we evaluated HuR tissue expression in a cohort of chronic healed and non healed leg ulcers. We also evaluated the effect of HuR knockdown on a number of cellular processes using the HaCaT human keratinocyte cell line. HuR was expressed in greater levels in the 'chronic healed' cohort of ulcers, compared to the 'chronic non-healed', although this failed to reach statistical significance (p=0.13). HuR knockdown resulted in greater cellular growth, faster progression through the cell cycle and reduced apoptosis. Furthermore, it reduced cellular adhesion rates without affecting migration. We, therefore, concluded that HuR promotes wound healing, primarily through its effect on cellular adhesion. It also slows cellular growth rate via its effect on both cell cycle progression and rates of apoptosis. PMID- 22086296 TI - Mediators released during human anaphylaxis. AB - A range of mediators are generated during anaphylaxis, with redundancy of effects, multiple overlapping pathways, and involvement of several cell types. Key steps in the reaction occur at the site of initial contact, and mediators may not be detectable systemically. Furthermore, the potencies of various mediators vary enormously, and clinical effects may occur below our level of detection. We also do not know what converts (amplifies) a local reaction into systemic anaphylaxis. Murine models have identified several novel mediators that may propagate and/or regulate this process and also indicate that circulating neutrophils may play an important role in reaction amplification. Differential expression of various genes within specific intracellular signalling pathways of mediator release may further explain the varying severities of anaphylactic reactions. As our knowledge of the mechanisms of activation, key mediators, and the regulation of mediator release improves, new treatments for prevention and acute management may emerge. PMID- 22086298 TI - Toll-like receptors in systemic lupus erythematosus: potential targets for therapeutic intervention. AB - Toll-like receptors (TLRs) have attracted increased attention in recent years, not only for their role in sensing conserved microbial components, but also in the realm of autoimmunity. Although TLRs are most widely known for their capacity to detect conserved motifs of infectious agents, mounting evidence indicates that these innate receptors also promote autoimmune conditions by causing uncontrolled autoinflammation as a result of chronic recognition of self. In response to the need for modern approaches to treatment of autoimmune diseases, several groups have begun investigating ways to target TLRs as new therapeutic options for autoimmune conditions. Here we discuss recent data describing advances in TLRs as therapeutic targets for treatment of autoimmune diseases, with a focus on systemic lupus erythematosus. PMID- 22086297 TI - Modulating toll-like receptor 7 and 9 responses as therapy for allergy and autoimmunity. AB - Type I allergic diseases, such as allergic rhinitis and asthma, depend on allergen-induced T-helper type 2 (Th2) cells and IgE-secreting plasma cells. Fortunately, this harmful immune response can be modified by engaging Toll-like receptor (TLR)7 and TLR9, offering hopes to allergy sufferers. While clinical trials employing synthetic ligands for TLR7 or TLR9 are under way, one can wonder whether TLR7 or TLR9 engagements may trigger inadvertent autoreactivity and/or Th1-/Th17-mediated tissue pathology. To neutralize such danger, we have pioneered the development of potent TLR9 pathway antagonists, inhibitory oligonucleotides (INH-ODNs), which work in a sequence-specific manner. Interestingly, INH-ODNs also have TLR7-inhibitory properties; however, these effects appear to be sequence independent and phosphorothioate backbone dependent. In B cells, co engagement of the B-cell receptor for antigen and TLR7 or TLR9 may influence how INH-ODNs impose their regulatory effects. INH-ODNs block TLR9 activation by competitively antagonizing ligand binding to proteolytically cleaved C-terminal TLR9 fragment. One may envision future use of INH-ODNs in systemic autoimmune diseases, DNA-mediated sepsis, or other situations in which chronic inflammation results from abnormal TLR7- and/or TLR9-mediated immune activation. PMID- 22086299 TI - Pro-inflammatory effects of the mushroom Agaricus blazei and its consequences on atherosclerosis development. AB - PURPOSE: Extracts of the mushroom Agaricus blazei (A. blazei) have been described as possessing immunomodulatory and potentially cancer-protective activities. However, these effects of A. blazei as a functional food have not been fully investigated in vivo. METHODS: Using apolipoprotein E-deficient (ApoE(-/-)) mice, an experimental model of atherosclerosis, we evaluated the effects of 6 or 12 weeks of A. blazei supplementation on the activation of immune cells in the spleen and blood and on the development of atherosclerosis. RESULTS: Food intake, weight gain, blood lipid profile, and glycemia were similar between the groups. To evaluate leukocyte homing and activation, mice were injected with (99m)Tc radiolabeled leukocytes, which showed enhanced leukocyte migration to the spleen and heart of A. blazei-supplemented animals. Analysis of the spleen showed higher levels of activation of neutrophils, NKT cells, and monocytes as well as increased production of TNF-alpha and IFN-gamma. Circulating NKT cells and monocytes were also more activated in the supplemented group. Atherosclerotic lesion areas were larger in the aorta of supplemented mice and exhibited increased numbers of macrophages and neutrophils and a thinner fibrous cap. A. blazei-induced transcriptional upregulation of molecules linked to macrophage activation (CD36, TLR4), neutrophil chemotaxy (CXCL1), leukocyte adhesion (VCAM 1), and plaque vulnerability (MMP9) were seen after 12 weeks of supplementation. CONCLUSIONS: This is the first in vivo study showing that the immunostimulatory effect of A. blazei has proatherogenic repercussions. A. blazei enhances local and systemic inflammation, upregulating pro-inflammatory molecules, and enhancing leukocyte homing to atherosclerosis sites without affecting the lipoprotein profile. PMID- 22086300 TI - Is a daily supplementation with 40 microgram vitamin D3 sufficient? A randomised controlled trial. AB - PURPOSE: The effect of 40 MUg (1,600 IU) per day of vitamin D(3) on serum 25 hydroxyvitamin D (25(OH)D) and markers of bone and mineral metabolism was evaluated. METHODS: This intervention study was designed as a double-blind randomised controlled trial. Forty-five community-dwelling subjects (32 females), age 55-84 years, at 58 degrees North latitude were supplemented for 1 year with 40 MUg vitamin D(3) plus 1,000 mg calcium per day, or with 1,000 mg calcium per day for controls. Safety parameters and 25(OH)D, intact parathyroid hormone (PTH), ionized calcium, bone-specific alkaline phosphatase (BALP), and tartrate resistant acid phosphatase isoform 5b (TRACP5b) were measured over the study period. RESULTS: All subjects supplemented with vitamin D(3) reached a 25(OH)D level above 50 nmol/L. Mean (SD) serum 25(OH)D increased from 50.4 (13.5) nmol/L to 84.2 (17.5) nmol/L, range 55.0-125.0 nmol/L in the vitamin D(3) supplemented group and the corresponding levels for the control group were 47.3 (14.1) nmol/L and 45.7 (13.4) nmol/L, range 26.0-73.0 nmol/L. No serious adverse event was recorded and the highest 25(OH)D level reached, 125.0 nmol/L, is well below toxic levels. BALP and TRACP5b did not change significantly over the study period. CONCLUSIONS: This trial suggests that a daily supplementation with 40 MUg vitamin D(3) is sufficient to secure a 25(OH)D level of 50 nmol/L. No side effects were observed in the study group. PMID- 22086301 TI - Protective effects of olive oil phenolics and gallic acid on hydrogen peroxide induced apoptosis. AB - PURPOSE: Olive oil contains several phenolic compounds possessing antioxidant activity. The aim of this study was to investigate the protective effects of olive oil phenolic extract (OOPE) and one of its constituents, gallic acid (GA) against H(2)O(2)-induced oxidative stress and apoptotic cell death in HeLa cells, a model for human epithelial cells. METHODS: The cells were pretreated with nontoxic doses of OOPE or GA for 4, 24 and 48 h, and the intracellular reactive oxygen species (ROS) level was determined, before and after oxidative stress induction with H(2)O(2). As an indicator of apoptosis, caspase 9 activity was measured. RESULTS: All pretreatments reduced ROS generation. Four hour incubation with OOPE or GA completely inhibited ROS generation. Increases in caspase 9 activity by OOPE and GA pretreatment under harsh stress conditions were inhibited 92 and 67.8%, respectively. CONCLUSIONS: These results suggest that OOPE and GA act as powerful antioxidants against oxidative stress and exert anti-apoptotic effects. PMID- 22086303 TI - Mutation and association analyses of the candidate genes ESR1, ESR2, MAX, PCNA, and KAT2A in patients with unexplained MSH2-deficient tumors. AB - Lynch syndrome (Hereditary non-polyposis colorectal cancer/HNPCC) is a cancer susceptibility syndrome which is caused by germline mutations in DNA mismatch repair (MMR) genes, in particular MLH1 and MSH2. A pathogenic germline mutation in the respective MMR gene is suggested by the finding of a loss of a mismatch repair protein in tumor tissue on immunohistochemical staining combined with an early age of onset and/or the familial occurrence of colorectal cancer. Pathogenic germline mutations are identifiable in around 60% of patients suspected of Lynch syndrome, depending on the familial occurrence. The aim of the present study was to identify novel susceptibility genes for Lynch syndrome. 64 Healthy controls and 64 Lynch syndrome patients with no pathogenic MSH2 mutation but a loss of MSH2 expression in their tumor tissue were screened for rare and disease causing germline mutations in the functional candidate genes ESR1, ESR2, MAX, PCNA, and KAT2A. Thirty variants were identified, and these were then genotyped in an independent sample of 36 mutation negative Lynch syndrome patients and 234 controls. Since a trend towards association was observed for KAT2A, an additional set of 21 tagging SNPs was analyzed at this locus in a final case-control sample of 142 mutation negative Lynch syndrome patients and 298 controls. The mutation analysis failed to reveal any rare disease-causing mutations. No association was found at the single-marker or haplotypic level for any common disease-modifying variant. The present results suggest that neither rare nor common genetic variants in ESR1, ESR2, MAX, PCNA, or KAT2A contribute to the development of Lynch syndrome. PMID- 22086304 TI - Hereditary leiomyomatosis and renal cell cancer presenting as metastatic kidney cancer at 18 years of age: implications for surveillance. AB - Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant syndrome characterized by skin piloleiomyomas, uterine leiomyomas and papillary type 2 renal cancer caused by germline mutations in the fumarate hydratase (FH) gene. Previously, we proposed renal imaging for FH mutation carriers starting at the age of 20 years. However, recently an 18-year-old woman from a Dutch family with HLRCC presented with metastatic renal cancer. We describe the patient and family data, evaluate current evidence on renal cancer risk and surveillance in HLRCC and consider the advantages and disadvantages of starting surveillance for renal cancer in childhood. We also discuss the targeted therapies administered to our patient. PMID- 22086305 TI - Different algorithms for glycemic control will yield different results. PMID- 22086306 TI - A highly parallelized framework for computationally intensive MR data analysis. AB - OBJECT: The goal of this study was to develop a comprehensive magnetic resonance (MR) data analysis framework for handling very large datasets with user-friendly tools for parallelization and to provide an example implementation. MATERIALS AND METHODS: Commonly used software packages (AFNI, FSL, SPM) were connected via a framework based on the free software environment R, with the possibility of using Nvidia CUDA GPU processing integrated for high-speed linear algebra operations in R. Three hundred single-subject datasets from the 1,000 Functional Connectomes project were used to demonstrate the capabilities of the framework. RESULTS: A framework for easy implementation of processing pipelines was developed and an R package for the example implementation of Fully Exploratory Network ICA was compiled. Test runs on data from 300 subjects demonstrated the computational advantages of a processing pipeline developed using the framework compared to non parallelized processing, reducing computation time by a factor of 15. CONCLUSION: The feasibility of computationally intensive exploratory analyses allows broader access to the tools for discovery science. PMID- 22086307 TI - Diffusion property differences of the lower leg musculature between athletes and non-athletes using 1.5T MRI. AB - OBJECT: To compare the differences in diffusion properties--namely fractional anisotropy (FA), three eigenvalues of the diffusion tensor (lambda1, lambda2, and lambda3), and apparent diffusion coefficient (ADC)--between athletically-trained and untrained lower leg musculature. MATERIALS AND METHODS: Twelve athletes (Group A) and 11 non-athletes (Group B) were recruited. All were females in their 20s. We scanned diffusion tensor images of both calves and compared FA, the three eigenvalues, and ADC in the gastrocnemius medialis, gastrocnemius lateralis, soleus (SOL), and anterior tibialis muscles between Groups A and B, and between the right and left sides, using two-factor fractional ANOVA. RESULTS: In all muscles of bilateral calves, all three eigenvalues and ADC were lower in Group A than in Group B, with statistically significant differences in all muscles for lambda1, lambda2, and lambda3 and ADC, with a P value of <0.01. Moreover, statistical differences were also found between right and left for lambda1, lambda2, and lambda3 (P < 0.05), and ADC (P < 0.01) of the SOL muscle. FA showed no statistically significant differences in any muscles. CONCLUSIONS: Our results indicate that training causes a decrease of the three eigenvalues and ADC, which we hypothesize is due to an increase of density of myofilaments in the intracellular space, and deformation of the cell induced by enlargement of extracellular components. PMID- 22086308 TI - Comment on: Cost-effectiveness of denosumab for the treatment of postmenopausal osteoporosis. PMID- 22086309 TI - Vertebral body bone strength: the contribution of individual trabecular element morphology. AB - SUMMARY: Although the amount of bone explains the largest amount of variability in bone strength, there is still a significant proportion unaccounted for. The morphology of individual bone trabeculae explains a further proportion of the variability in bone strength and bone elements that contribute to bone strength depending on the direction of loading. INTRODUCTION: Micro-CT imaging enables measurement of bone microarchitecture and subsequently mechanical strength of the same sample. It is possible using micro-CT data to perform morphometric analysis on individual rod and plate bone trabeculae using a volumetric spatial decomposition algorithm and hence determine their contribution to bone strength. METHODS: Twelve pairs of vertebral bodies (T12/L1 or L4/L5) were harvested from human cadavers, and bone cubes (10 * 10 * 10 mm) were obtained. After micro-CT imaging, a volumetric spatial decomposition algorithm was applied, and measures of individual trabecular elements were obtained. Bone strength was measured in compression, where one bone specimen from each vertebral segment was tested supero-inferiorly (SI) and the paired specimen was tested antero-posteriorly (AP). RESULTS: Bone volume fraction was the strongest individual determinant of SI strength (r(2) = 0.77, p < 0.0001) and AP (r(2) = 0.54, p < 0.0001). The determination of SI strength was improved to r(2) = 0.87 with the addition of mean rod length and relative plate bone volume fraction. The determination of AP strength was improved to r(2) = 0.85 with the addition of mean rod volume and relative rod bone volume fraction. CONCLUSIONS: Microarchitectural measures of individual trabeculae that contribute to bone strength have been identified. In addition to the contribution of BV/TV, trabecular rod morphology increased the determination of AP strength by 57%, whereas measures of trabecular plate and rod morphology increased determination of SI strength by 13%. Decomposing vertebral body bone architecture into its constituent morphological elements shows that trabecular element morphology has specific functional roles to assist in maintaining skeletal integrity. PMID- 22086310 TI - Quality of life and health status with zoledronic acid and generic alendronate--a secondary analysis of the Rapid Onset and Sustained Efficacy (ROSE) study in postmenopausal women with low bone mass. AB - SUMMARY: The ROSE study compared annual infusion with zoledronic acid and weekly generic alendronate. No significant differences in quality of life or health status between treatment groups were observed. Adherence to alendronate during the study was high, with 80.9% of patients achieving adequate adherence. INTRODUCTION: A secondary analysis to evaluate quality of life, health status, adherence to alendronate and therapy preference in postmenopausal women with low bone mass who received treatment with zoledronic acid or alendronate was conducted. METHODS: Postmenopausal women with low bone mass were randomised 2:1 to receive an annual infusion of zoledronic acid or weekly oral generic alendronate in this open-label, multicentre study. Changes in quality of life and health status were assessed using questionnaires at baseline and month 12. Adherence to alendronate was assessed by the investigator and/or study personnel, and subjective therapy preference was assessed using a questionnaire at month 12. RESULTS: Patients were randomised to zoledronic acid (n = 408) and alendronate (n = 191). Overall, there were no significant differences in quality of life between zoledronic acid and alendronate. However, improvements in quality of life with zoledronic acid versus alendronate could be detected by posthoc analysis in patients with previous fractures. There were no significant differences in health status between patients receiving zoledronic acid or alendronate. Adherence to alendronate during the study was high, with 80.9% of patients achieving adequate adherence. A total of 81% of patients who had received zoledronic acid indicated that they would prefer to continue with that treatment, and 43% of the patients who received oral alendronate would like to switch to zoledronic acid. CONCLUSIONS: There were no significant differences in quality of life between patients receiving zoledronic acid or alendronate. PMID- 22086311 TI - Regional and age-related variations in the proportions of hip fractures and major fractures among postmenopausal women: the Global Longitudinal Study of Osteoporosis in Women. AB - We examined variations in proportions of hip fractures and major fractures among postmenopausal women using the Global Longitudinal Study of Osteoporosis in Women (GLOW). The proportion of major fractures that were hip fractures varied with age and region, whereas variations in the proportion of fractures that were major fractures appeared modest. INTRODUCTION: In many countries, the World Health Organization fracture risk assessment tool calculates the probability of major fractures by assuming a uniform age-associated proportion of major fractures that are hip fractures in different countries. We further explored this assumption, using data from the GLOW. METHODS: GLOW is an observational population-based study of 60,393 non-institutionalized women aged >=55 years who had visited practices within the previous 2 years. Main outcome measures were self-reported prevalent fractures after the age of 45 years and incident fractures during the 2 years of follow-up. RESULTS: The adjusted proportion of prevalent and incident major fractures after the age of 45 years that were hip fractures was higher in North America (16%, 17%) than in northern (13%, 12%) and southern Europe (10%, 10%), respectively. The proportion of incident major fractures that were hip fractures increased more than five-fold with age, from 6.6% among 55-59-year-olds to 34% among those aged >=85 years. Regional and age-associated variations in the proportion of all incident fractures that were major fractures were less marked, not exceeding 16% and 28%, respectively. CONCLUSIONS: The data suggest that there may be regional differences in the proportion of major fractures that are hip fractures in postmenopausal women. In contrast, the regional and age-related variations in the proportion of fractures that are major fractures appear to be modest. However, because of the limited number of fractures in our sample, further studies are necessary to confirm these findings. PMID- 22086313 TI - [The information in gastroenterology and internet]. PMID- 22086312 TI - Elevation of both reactive oxygen species and antioxidant enzymes in vein tissue of infertile men with varicocele. AB - OBJECTIVE: To compare reactive oxygen species (ROS) and antioxidants in internal spermatic vein tissue of men with varicocele and a control group with inguinal hernia. Also to compare the levels of oxidants and antioxidants in infertile and fertile men with varicocele. PATIENTS AND METHODS: 48 varicocele patients and 12 non-varicocele inguinal hernia patients participated in this study. The varicocele group was again divided into two groups--fertile men with varicocele and infertile men with varicocele. Internal spermatic vein tissue samples were obtained. The level of the malondialdehyde (MDA), an indicator of oxidative stress, and the activities of antioxidant enzymes (defense systems) against oxidative stress such as superoxide dismutase (SOD) and catalase (CAT) were estimated in these tissue samples. RESULTS: The mean level of MDA in the varicocele group was significantly higher than in the hernia group, whereas the levels of antioxidants (SOD and CAT) were significantly lower in the varicocele group than in the hernia group. When compared with the subgroups of the varicocele group, the MDA levels and SOD and CAT activities were significantly higher in the infertile varicocele group than in the fertile varicocele group. CONCLUSIONS: Antioxidant enzyme levels generally decrease due to a high consumption in varicocele patients. On the contrary, in our study both MDA and antioxidant enzymes increased in the internal spermatic venous wall of infertile varicocele patients. This situation may be explained by an adaptation against oxidative stress in varicocele, which could be defined as a chronic process. PMID- 22086314 TI - [Use of cyanoacrylate in the endoscopic therapy of gastric varices: experience in the National Hospital Edgardo Rebagliati Martins from 2006 to 2010]. AB - OBJECTIVE: To evaluate the therapeutic success of the injection of N-butyl-2 cyanoacrylate in the treatment of gastric varices. METHODS: Cross-sectional study included 33 patients with gastric varices who only received cyanoacrylate endoscopic therapy between 2006 and 2010. Intravariceally, cyanoacrylate was injected in a 1:1 dilution with lipiodol until the obliteration of varices. The therapeutic situation was: active bleeding, varices with stigmata of recent bleeding and secondary prophylaxis. Treatment success was evaluated according to hemostasis, recurrent bleeding and obliteration. RESULTS: Of the 33 patients, 3 (9.1%) were for active bleeding, 20 (60.6%) with stigmata of recent bleeding and 10 (30.3%) as secondary prophylaxis. Gastric varices were GOV2, 17 (51.5%); IGV1, 14 (42.4%); GOV1, 2 (6.1%). Hemostasis was achieved in 21 (91.3%) and in 2 (66.7%) of 3 patients with active bleeding. Five (15.6%) patients had recurrent bleeding and 2 of them used cyanoacrylate with successful hemostasis. Obliteration was achieved. Four patients died and one for failure of control bleeding. A high severity of Child-Pugh classification was related to treatment endoscopic failure (p=0.034). The main complication was bleeding after the injection of cyanoacrylate. CONCLUSIONS: Our results support the use of cyanoacrylate in the treatment of gastric varices with few major complications. PMID- 22086315 TI - [Fecal leukocytes in children with acute diarrhea: time to reconsider the clinical usefulness of the test?]. AB - INTRODUCTION: Fecal leukocytes are widely used to identify invasive diarrhea and to make then the decision of prescribing or not antibiotics. This test has been hardly assessed in small hospitals of developing countries with efficient laboratory processes. We aimed to assess the diagnostic performance of different thresholds of fecal leukocytes in children under-five with acute diarrhea. MATERIAL AND METHODS: Retrospective study of clinical and laboratory records in the Pediatric Emergency Hospital, Lima, Peru. All cases with a stool culture and fecal leukocytes independently and systematically performed were studied. Sensitivity, specificity, predictive values, likelihood ratios (LR), and receiver operating characteristics (ROC) curves were calculated. RESULTS: Out of 1,804 stool samples assessed, 901 (49,9%) were positive for one or more bacterial entheropathogens. Sensitivity (Sn), specificity (Sp), and positive LR varied for different thresholds: more than 5 (S: 93.2%, Sp: 21.9%, LR+:), more than 20 (Sn: %, Sp: %,+LR: ), more than 50 (Sn: 74.9%, Sp: 56.7%, +LR: 1.73), and more than 100 fecal leukocytes per high power field (Sn: 60.7%, Sp: 71.9%, LR+: 2.17). The general area under the ROC curve was 0.69 (CI 95%: 0.67-0.72). CONCLUSIONS: Diagnostic performance of fecal leukocytes is suboptimal and may not warrant its continued use in developing settings, as it promotes antibiotic abuse, and on the other hand increases the risk of overlooking patients with invasive diarrhea who may Benedit from antibiotic treatment. Combination of epidemiological and clinical data with either fecal leukocytes or fecal lactoferrin may provide a more efficient approach. PMID- 22086316 TI - [Antimicrobial susceptibility of helicobacter pylori to levofloxacin determined in a miniwell format and disk diffusion tests using egg yolk agar]. AB - OBJECTIVES: To determine the Minimum inhibitory concentration (MIC) of Levofloxacin against HELICOBACTER PYLORI (HP). MATERIALS AND METHODS: 95 HP Peruvian strains were evaluated in Agar dilution and Disk diffusion tests, as well as the Pearson Coefficient (r) and the inoculum's effect. RESULTS: 36.9% (35 of 95) were resistant (MIC>1 MUg/ml) to Levofloxacin. MIC90 was 16 ug/ml (CI:90%). MIC of Levofloxacin did not change at different inoculum concentrations. r: -0.733 (p<0.001). CONCLUSIONS: The proportion of HP Levofloxacin resistant strains in Peru is higher than in developed countries. Periodic testing of antibiotic susceptibility is warranted to select the most accurate therapies. PMID- 22086317 TI - [Score BISAP validation as a prognostic system in acute pancreatitis]. AB - BACKGROUND: The BISAP score is a simple system, which englobes clinical features (laboratory and imagenology tests) allowing to predict the mortality in acute pancreatitis within the first 24 hours of hospitalization. OBJECTIVE: To determine the validity of the BISAP score in the prediction of prognosis and severity of acute pancreatitis. METHOD: In order to validate the BISAP score, a study was performed in 57 patients with a diagnosis of acute pancreatitis at the moment of admission. The reference test was the Atlanta criteria which confirmed severe clinical course beyond the fifth day, in many cases supported by CT. RESULTS: 71.9% were women. The mean age was 45.33 years. Biliary lithiasis was the most frequent cause (66.7%). According to the reference test 71.9% were mild and 28.1% severe. According to the BISAP score 77.2% mild and 22.8% severe. The sensitivity and specificity for the BISAP score was of 75% and 97.56% respectively. The predictive positive value was 92.31% and the predictive negative value was 90.91%. CONCLUSIONS: The BISAP score allows to predict the severity of the acute pancreatitis. PMID- 22086318 TI - [Identifying the severe acute pancreatitis]. AB - AIMS: To compare patients with acute necrotizing pancreatitis without any additional complications during their hospital stay (Group A) versus patients with Acute Necrotizing Pancreatitis with additional complications during their hospital stay (Group B). METHODS: Data obtained from a pre-existing base from hospitalized patients with diagnosis of acute necrotizing pancreatitis in the specialized unit of "Unidad de Pancreatitis Aguda Grave del Hospital Nacional Edgardo Rebagliati Martins" between 2000 and 2010. Data included patients with diagnosis of acute necrotizing pancreatitis, of ages 18 and over. RESULTS: Data from 215 patients with acute necrotizing pancreatitis was included. Patients from Group A represented 32% (68) and from Group B 68% (147). Group A had a average of 39 hospitalized days and Group B had an average of 56 days (p=0.01). From Group A 22% had more than 50% of necrosis while 43% of Group B had this extension of necrosis (p <0.05, OR 3.4, IC (1.12-10)). Of the 14 deaths of the population, all part of Group B, 12 of them had more than 50% of necrosis. CONCLUSIONS: Not every patient classified as severe acute pancreatitis, based on the presence of necrosis, behave likewise. It is an extended necrosis, described as more than 50% of pancreatic necrosis, and not the presence itself which will determine additional complications during the course of disease and a greater mortality. PMID- 22086319 TI - [Use of Foley's catheter to control abdominal wall bleeding in the trocar insertion place during laparoscopic surgery]. AB - BACKGROUND: Abdominal wall bleeding in the port-site insertion place during laparoscopic surgery is sometimes difficult to control and can be associated with morbidity ranging from parietal pain up to haematoma and massive haemoperitoneum. PATIENTS AND METHODS: We perform a retrospective study of our experience in the management of the abdominal wall bleeding port-site using a Foley's catheter (24F), in those cases when haemostasis with electrocautery was not achieved. RESULTS: This technique was used in 35 patients (27 women and 8 men) with a mean age of 45,37 years (range 24-82 years). The median of time up to the removal of the catheter was 36 hours (range 24-48 hours), without observing bleeding or prolongation of the hospital stay or readmission. CONCLUSIONS: The use of Foley's catheter is a simple and efficient method for the control of the port-site bleeding during laparoscopic surgery. PMID- 22086320 TI - [Gastroenterology 2.0: useful resources for the gastroenterologist available on the Web 2.0]. AB - The term Web 2.0 refers to the use of Internet applications which enable the users to share, participate and collaborate together on information. The objective of this study is to check different applications that use Web 2.0, which could help the gastroenterologist in his daily practice. The applications that will be checked include: blogs, microblogging, RSS, podcasts, wikis and social networks. "Gastroenterology 2.0" represents the applications, services, and tools based on Web 2.0, which are of easy use and easily accessible - to consumers, patients, gastroenterologists and other health professionals, as well as researchers. Although several studies have shown the benefits these technologies have on the medical practice, it is necessary to conduct further studies to demonstrate the use of these applications on improving health. PMID- 22086321 TI - [Clinical practice guidelines on the diagnosis and treatment of infectious acute diarrhea in children Peru - 2011]. AB - The Clinical Practice Guidelines cover the Diagnosis and Treatment of Acute Diarrhea in Pediatric Infectious is a consice information about definition, inclusion and exclusion criteria; epidemiology and etiology of infectious diarrhea. The guidelines cover aspects of diagnosis and treatment (dehydration, antibiotics, supportive therapy), nutritional support and other aspects of transferences and prevention. PMID- 22086322 TI - [Celiac disease and intestinal obstruction by T cell lymphoma]. AB - A male patient, 55 years old, born in Ayacucho, with Spanish ancestors, was hospitalized through emergency referring abdominal pain, and 10 kilograms weight loss. Six months before he was diagnosed as having irritable bowel syndrome. His previous diseases were rheumatoid arthritis and intolerance to lactose. Laboratory results were: Hb 12 gr./dL, white cells 5200 per mm3, albumin 2.7 gr./dL, erythrocyte sedimentation rate 32 mm/hr., and tumor markers were negative. Radiographic study of the small bowel showed barium fragmentation, and a focal dilation in distal jejunum. Chest X-ray and CT scan of thorax, abdomen and pelvis were normal. Colonoscopy was normal for colonic mucosa, but in ileum it showed an irregular mucosa, little nodules and fewer folds than usual. Biopsy from ileum demonstrated unspecific inflammation. Upper endoscopy showed gastritis, a duodenum scar ulcer and an irregular mosaic pattern pink and white. Duodenum biopsy demonstrated short villi, chronic inflammation and an increase in the number of intraepithelial lymphocytes, all these was consistent with celiac disease Marsh 3. Antibodies anti-endomisium and anti-transglutaminase were positive. After some days he developed signs of bowel obstruction and was operated. PMID- 22086323 TI - [Metastatic primary gastric adenocarcinoma in amigdala]. AB - We report the case of a 79 years old female patient, with a one year history of dysphagia, presence of a tumor in the right palatine tonsil and cervical lymph node involvement. A biopsy of the palatine tonsil tumor informed as an adenocarcinoma was performed followed by a gastroscopy that reported a lesion in gastric body and antrum whose histologycal diagnosis was a moderately differentiated tubular adenocarcinoma. The patient received chemotherapy with 5FU. We present this case due to the unusual presentation of metastasis to the palatine tonsil and also for being the first manifestation of a gastric cancer. PMID- 22086324 TI - [Gastrointestinal Epstein Barr virus positive diffuse large B cell lymphoma in elderly: report of five cases and review of literature]. AB - EBV-positive diffuse large B-cell lymphoma (DLBCL) in elderly is a new entity included provisionally in the most recent WHO Classification of lymphoid neoplasms. It usually affects elderly patients and has a poor survival. The goal of this report was to evaluate clinical, endoscopic characteristics and survival of five patients with this entity and gastrointestinal afectation. From five cases, three cases had gastric infiltration, one ileon and one in cecum. PMID- 22086325 TI - [Jejunal GIST with obscure gastrointestinal bleeding]. AB - We report the case of a woman of 84 years with a history of cardiac arrhythmia and hemorrhoids. She had multiple hospitalizations and transfusions for symptomatic iron deficiency anemia, endoscopic studies showed only small diverticula and colon polyps. He was later hospitalized with bloody stools red wines, upper endoscopy and colonoscopy showed gastritis, small colonic ulcers, colonic polyp and multiple diverticula. Readmitted with bleeding of obscure origin, on that occasion showed gastritis, antral erosions, small ulcers, colon polyps and colon ulcers in the process of healing, capsule endoscopy showed angiodysplasia in jejunum, anterograde enteroscopy detected some erythematous lesions in proximal jejunum without evidence of bleeding. Again hospitalized for melena and abdominal. PMID- 22086326 TI - Application of a novel score test for genetic association incorporating gene-gene interaction suggests functionality for prostate cancer susceptibility regions. AB - AIMS: We introduce an innovative multilocus test for disease association. It is an extension of an existing score test that gains power over alternative methods by incorporating a parsimonious one-degree-of-freedom model for interaction. We use our method in applications designed to detect interactions that generate hypotheses about the functionality of prostate cancer (PRCA) susceptibility regions. METHODS: Our proposed score test is designed to gain additional power through the use of a retrospective likelihood that exploits an assumption of independence between unlinked loci in the underlying population. Its performance is validated through simulation. The method is used in conditional scans with data from stage II of the Cancer Genetic Markers of Susceptibility PRCA genome wide association study. RESULTS: Our proposed method increases power to detect susceptibility loci in diverse settings. It identified two high-ranking, biologically interesting interactions: (1) rs748120 of NR2C2 and subregions of 8q24 that contain independent susceptibility loci specific to PRCA and (2) rs4810671 of SULF2 and both JAZF1 and HNF1B that are associated with PRCA and type 2 diabetes. CONCLUSIONS: Our score test is a promising multilocus tool for genetic epidemiology. The results of our applications suggest functionality for poorly understood PRCA susceptibility regions. They motivate replication study. PMID- 22086328 TI - Assessment of density functional theory for bonds formed between rare gases and open-shell atoms: a computational study of small molecules containing He, Ar, Kr and Xe. AB - The validity of the description of the DFT approximations currently implemented in plane wave DFT codes (LDA, GGA, meta-GGA, hybrid, GGA + empirical dispersion correction) for interactions between rare gases and open-shell atoms which form materials is poorly known. We have performed a first assessment of the accuracy of these functionals for the description of the bonds formed by helium, argon, krypton and xenon with various open-shell atoms. This evaluation has been done on model molecular systems for which precise experimental data are available and reference post-Hartree-Fock calculations (CCSD(T) using large basis sets) are feasible. The results show that when the rare gas atom shares density with the neighbouring atoms, the GGA functionals yield good geometries and qualitatively correct binding energies, even if these are quite significantly overestimated. The use of hybrid functionals enables us to obtain good geometries and satisfactory binding energies. For compounds in which the rare gas atom forms weak dispersive-like bonding, the accuracy yielded by the various functionals is not as good. No functional gives satisfactory binding energies for all the compounds investigated. Several GGA and hybrid functionals yield correct geometries, even if some isomers are not obtained. One GGA functional (PBE) yields qualitatively correct results for the compounds of the three rare gases and several hybrid functionals give satisfactory energies for He compounds. The addition of an empirical dispersive correction improves the results on association compounds, but several isomers are not found. PMID- 22086327 TI - Computational modeling of temperature elevation and thermoregulatory response in the brains of anesthetized rats locally exposed at 1.5 GHz. AB - The dominant effect of human exposures to microwaves is caused by temperature elevation ('thermal effect'). In the safety guidelines/standards, the specific absorption rate averaged over a specific volume is used as a metric for human protection from localized exposure. Further investigation on the use of this metric is required, especially in terms of thermophysiology. The World Health Organization (2006 RF research agenda) has given high priority to research into the extent and consequences of microwave-induced temperature elevation in children. In this study, an electromagnetic-thermal computational code was developed to model electromagnetic power absorption and resulting temperature elevation leading to changes in active blood flow in response to localized 1.457 GHz exposure in rat heads. Both juvenile (4 week old) and young adult (8 week old) rats were considered. The computational code was validated against measurements for 4 and 8 week old rats. Our computational results suggest that the blood flow rate depends on both brain and core temperature elevations. No significant difference was observed between thermophysiological responses in 4 and 8 week old rats under these exposure conditions. The computational model developed herein is thus applicable to set exposure conditions for rats in laboratory investigations, as well as in planning treatment protocols in the thermal therapy. PMID- 22086329 TI - Facile in situ copper(II) mediated C-S bond activation transforming dithiocarbimate to carbamate and thiocarbamate generating Cu(II) and Cu(I) complexes. AB - Facile in situ Cu(II) mediated transformation of p-tolylsulfonyldithiocarbimate in conjunction with polypyridyl or phosphine ligands into corresponding carbamate and thiocarbamate led to the formation of new copper complexes with varying nuclearities and geometries, via C-S bond activation of the ligand within identical reaction systems. PMID- 22086330 TI - Integrin-mediated signaling contributes to gadolinium-containing-particle promoted cell survival and G1 to S phase cell cycle transition by enhancing focal adhesion formation. AB - We previously reported that Gd-containing particles formed under physiological conditions act as active entities to enhance cell survival and promote S phase entry via activation of both mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase/Akt signaling pathways. However, how they transduce the extracellular signal inside the cell remains unclear. The present study demonstrates that Gd-containing particles can alleviate serum-deprivation-induced cell death and promote G1 to S phase cell cycle progression by enhancing cell adhesion to the extracellular matrix. As an indicator of adhesion, the vinculin distribution was detected by confocal laser scanning microscopy. The control cells exhibited fewer and less typical focal adhesions. After treatment with Gd-containing particles, a large number of vinculin-containing focal adhesions were maintained. In the presence of integrin antagonists, the percentage of S phase entry induced by Gd-containing particles was decreased and the enhancement of cell viability was also attenuated, along with a decrease in both cyclin D expression and ERK phosphorylation. In summary, the present results suggest that the integrin mediated signaling pathway plays an important role in cell survival and G1 to S phase transition promoted by Gd-containing particles by enhancing focal adhesion formation. The results presented here provide novel evidence to advance knowledge leading to further understanding of the mechanisms of both cell proliferation and cell survival promoted by Gd and may be helpful for developing effective measures to prevent or treat nephrogenic systemic fibrosis. PMID- 22086331 TI - Transient MPK6 activation in response to oxygen deprivation and reoxygenation is mediated by mitochondria and aids seedling survival in Arabidopsis. AB - Mitogen-activated protein kinases (MPKs) are regulated by diverse stresses with a reactive oxygen species (ROS) component. Here, we report the rapid and transient activation of MPK3, MPK4 and MPK6 upon oxygen deprivation as well as reoxygenation in seedlings of Arabidopsis thaliana. MPK activation peaked within 2 h of oxygen deprivation and again at a higher magnitude within 5 min of reoxygenation. MPK6 was the predominant kinase regulated by oxygen availability in both aerial and root tissue, except in mpk6 mutants, which displayed compensatory activation of MPK3. A universal consequence of oxygen deprivation in eukaryotes is inhibition of the terminal step of the mitochondrial electron transport chain (mETC). We demonstrate that treatment of seedlings with the mETC inhibitors antimycin A and potassium cyanide under normoxia promotes transient MPK6 and MPK3 activation. Confocal imaging of seedlings provided evidence that both oxygen deprivation and mETC inhibitors stimulate mitochondria-associated ROS production. We found that seedling survival of prolonged oxygen deprivation was improved in transgenics that ectopically overexpress MPK3, MPK4 and MPK6, but the induction of mRNAs associated with low oxygen acclimation responses were not markedly altered in MPK6 overexpression lines or mpk6 loss-of-function mutants. However, distinctions in MPK6 activation potential were correlated with other differences in mRNAs accumulation. Our findings suggest that oxygen deprivation and reoxygenation trigger mitochondrial ROS production to activate MPK signaling, which in turn regulate reversible processes that aid survival of transient oxygen deprivation. PMID- 22086332 TI - Genome evolution in diploid and tetraploid Coffea species as revealed by comparative analysis of orthologous genome segments. AB - Sequence comparison of orthologous regions enables estimation of the divergence between genomes, analysis of their evolution and detection of particular features of the genomes, such as sequence rearrangements and transposable elements. Despite the economic importance of Coffea species, little genomic information is currently available. Coffea is a relatively young genus that includes more than one hundred diploid species and a single tetraploid species. Three Coffea orthologous regions of 470-900 kb were analyzed and compared: both subgenomes of allotetraploid Coffea arabica (contributed by the diploid species Coffea eugenioides and Coffea canephora) and the genome of diploid C. canephora. Sequence divergence was calculated on global alignments or on coding and non coding sequences separately. A search for transposable elements detected 43 retrotransposons and 198 transposons in the sequences analyzed. Comparative insertion analysis made it possible to locate 165 TE insertions in the phylogenetic tree of the three genomes/subgenomes. In the tetraploid C. arabica, a homoeologous non-reciprocal transposition (HNRT) was detected and characterized: a 50 kb region of the C. eugenioides derived subgenome replaced the C. canephora derived counterpart. Comparative sequence analysis on three Coffea genomes/subgenomes revealed almost perfect gene synteny, low sequence divergence and a high number of shared transposable elements. Compared to the results of similar analysis in other genera (Aegilops/Triticum and Oryza), Coffea genomes/subgenomes appeared to be dramatically less diverged, which is consistent with the relatively recent radiation of the Coffea genus. Based on nucleotide substitution frequency, the HNRT was dated at 10,000-50,000 years BP, which is also the most recent estimation of the origin of C. arabica. PMID- 22086333 TI - MYB80, a regulator of tapetal and pollen development, is functionally conserved in crops. AB - The Arabidopsis AtMYB80 transcription factor (formerly AtMYB103) regulate genes essential for tapetal and pollen development. One of these genes, coding for an aspartic protease (UNDEAD), may control the timing of tapetal programmed cell death (PCD). In crop plants such as rice and wheat, abiotic stresses lead to abnormal tapetal development resulting in delayed PCD. Manipulation of AtMYB80 function has been used to develop a reversible male sterility system applicable to hybrid crop production. MYB80 homologs were cloned from wheat, rice, canola and cotton. The promoters of the homologs drove temporal and spatial expression patterns of the GUS reporter gene in the tapetum and microspores of Arabidopsis anthers identical to the AtMYB80 promoter. A short region is conserved in all five MYB80 promoters. The MYB80 homolog genes, driven by the AtMYB80 or their respective promoters, rescued the atmyb80 mutant, completely restoring male fertility. The canola MYB80 was fused to the EAR (ERF-associated amphiphilic repression) repressor and canola plants transgenic for the construct exhibited premature tapetal degradation and subsequent pollen abortion. The five MYB80 homologs all shared a 44 amino acid sequence immediately adjacent to the R2R3 domain which appears to be necessary for MYB80 function. PMID- 22086335 TI - Tactile stimulation lowers stress in fish. AB - In humans, physical stimulation, such as massage therapy, reduces stress and has demonstrable health benefits. Grooming in primates may have similar effects but it remains unclear whether the positive effects are due to physical contact or to its social value. Here we show that physical stimulation reduces stress in a coral reef fish, the surgeonfish Ctenochaetus striatus. These fish regularly visit cleaner wrasses Labroides dimidiatus to have ectoparasites removed. The cleanerfish influences client decisions by physically touching the surgeonfish with its pectoral and pelvic fins, a behaviour known as tactile stimulation. We simulated this behaviour by exposing surgeonfish to mechanically moving cleanerfish models. Surgeonfish had significantly lower levels of cortisol when stimulated by moving models compared with controls with access to stationary models. Our results show that physical contact alone, without a social aspect, is enough to produce fitness-enhancing benefits, a situation so far only demonstrated in humans. PMID- 22086334 TI - MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a. AB - DNA CpG methylation and histone H3 lysine 9 (H3K9) methylation are two major repressive epigenetic modifications, and these methylations are positively correlated with one another in chromatin. Here we show that G9a or G9a-like protein (GLP) dimethylate the amino-terminal lysine 44 (K44) of mouse Dnmt3a (equivalent to K47 of human DNMT3A) in vitro and in cells overexpressing G9a or GLP. The chromodomain of MPP8 recognizes the dimethylated Dnmt3aK44me2. MPP8 also interacts with self-methylated GLP in a methylation-dependent manner. The MPP8 chromodomain forms a dimer in solution and in crystals, suggesting that a dimeric MPP8 molecule could bridge the methylated Dnmt3a and GLP, resulting in a silencing complex of Dnmt3a-MPP8-GLP/G9a on chromatin templates. Together, these findings provide a molecular explanation, at least in part, for the co-occurrence of DNA methylation and H3K9 methylation in chromatin. PMID- 22086336 TI - Electric field-induced chemical locomotion of conducting objects. AB - Externally triggered motion of small objects has potential in applications ranging from micromachines, to drug delivery, and self-assembly of superstructures. Here we present a new concept for the controlled propulsion of conducting objects with sizes ranging from centimetres to hundreds of micrometres. It is based on their polarization, induced by an electric field, which triggers spatially separated oxidation and reduction reactions involving asymmetric gas bubble formation. This in turn leads to a directional motion of the objects. Depending on the implied redox chemistry and the device design, the speed can be controlled and the motion can be switched from linear to rotational. This type of chemical locomotion is an alternative to existing approaches based on other principles. PMID- 22086337 TI - Pore surface engineering in covalent organic frameworks. AB - Covalent organic frameworks (COFs) are a class of important porous materials that allow atomically precise integration of building blocks to achieve pre-designable pore size and geometry; however, pore surface engineering in COFs remains challenging. Here we introduce pore surface engineering to COF chemistry, which allows the controlled functionalization of COF pore walls with organic groups. This functionalization is made possible by the use of azide-appended building blocks for the synthesis of COFs with walls to which a designable content of azide units is anchored. The azide units can then undergo a quantitative click reaction with alkynes to produce pore surfaces with desired groups and preferred densities. The diversity of click reactions performed shows that the protocol is compatible with the development of various specific surfaces in COFs. Therefore, this methodology constitutes a step in the pore surface engineering of COFs to realize pre-designed compositions, components and functions. PMID- 22086338 TI - Functionalized arrays of Raman-enhancing nanoparticles for capture and culture free analysis of bacteria in human blood. AB - Detecting bacteria in clinical samples without using time-consuming culture processes would allow rapid diagnoses. Such a culture-free detection method requires the capture and analysis of bacteria from a body fluid, which are usually of complicated composition. Here we show that coating Ag-nanoparticle arrays with vancomycin (Van) can provide label-free analysis of bacteria via surface-enhanced Raman spectroscopy (SERS), leading to a ~1,000-fold increase in bacteria capture, without introducing significant spectral interference. Bacteria from human blood can be concentrated onto a microscopic Van-coated area while blood cells are excluded. Furthermore, a Van-coated substrate provides distinctly different SERS spectra of Van-susceptible and Van-resistant Enterococcus, indicating its potential use for drug-resistance tests. Our results represent a critical step towards the creation of SERS-based multifunctional biochips for rapid culture- and label-free detection and drug-resistant testing of microorganisms in clinical samples. PMID- 22086339 TI - Ultrafast direct modulation of a single-mode photonic crystal nanocavity light emitting diode. AB - Low-power and electrically controlled optical sources are vital for next generation optical interconnect systems to meet strict energy demands. Current optical transmitters consisting of high-threshold lasers plus external modulators consume far too much power to be competitive with future electrical interconnects. Here we demonstrate a directly modulated photonic crystal nanocavity light-emitting diode (LED) with 10 GHz modulation speed and less than 1 fJ per bit energy of operation, which is orders of magnitude lower than previous solutions. The device is electrically controlled and operates at room temperature, while the high modulation speed results from the fast relaxation of the quantum dots used as the active material. By virtue of possessing a small mode volume, our LED is intrinsically single mode and, therefore, useful for communicating information over a single narrowband channel. The demonstrated device is a major step forward in providing practical low-power and integrable sources for on-chip photonics. PMID- 22086340 TI - Self-assembly of DNA nanotubes with controllable diameters. AB - The synthesis of DNA nanotubes is an important area in nanobiotechnology. Different methods to assemble DNA nanotubes have been reported, and control over the width of the nanotubes has been achieved by programmed subunits of DNA tiles. Here we report the self-assembly of DNA nanotubes with controllable diameters. The DNA nanotubes are formed by the self-organization of single-stranded DNAs, exhibiting appropriate complementarities that yield hexagon (small or large) and tetragon geometries. In the presence of rolling circle amplification strands, that exhibit partial complementarities to the edges of the hexagon- or tetragon building units, non-bundled DNA nanotubes of controlled diameters can be formed. The formation of the DNA tubes, and the control over the diameters of the generated nanotubes, are attributed to the thermodynamically favoured unidirectional growth of the sheets of the respective subunits, followed subjected to the folding of sheets by elastic-energy penalties that are compensated by favoured binding energies. PMID- 22086341 TI - Selective dispersion of high purity semiconducting single-walled carbon nanotubes with regioregular poly(3-alkylthiophene)s. AB - Conjugated polymers, such as polyfluorene and poly(phenylene vinylene), have been used to selectively disperse semiconducting single-walled carbon nanotubes (sc SWNTs), but these polymers have limited applications in transistors and solar cells. Regioregular poly(3-alkylthiophene)s (rr-P3ATs) are the most widely used materials for organic electronics and have been observed to wrap around SWNTs. However, no sorting of sc-SWNTs has been achieved before. Here we report the application of rr-P3ATs to sort sc-SWNTs. Through rational selection of polymers, solvent and temperature, we achieved highly selective dispersion of sc-SWNTs. Our approach enables direct film preparation after a simple centrifugation step. Using the sorted sc-SWNTs, we fabricate high-performance SWNT network transistors with observed charge-carrier mobility as high as 12 cm(2) V(-1) s(-1) and on/off ratio of >10(6). Our method offers a facile and a scalable route for separating sc-SWNTs and fabrication of electronic devices. PMID- 22086342 TI - A gustatory receptor involved in host plant recognition for oviposition of a swallowtail butterfly. AB - Swallowtail butterflies belonging to the family of Papilionidae selectively utilize a limited number of plants from a single or a few families. Female butterflies lay eggs on their host only when they detect specific chemicals through their foreleg chemosensilla while drumming on the leaf surface. Here we show that the butterfly, Papilio xuthus, uses a gustatory receptor specific for synephrine to select its host in oviposition behaviour. We identify a gustatory receptor gene involved in the recognition of an oviposition stimulant, synephrine, from the P. xuthus by a combination of in silico, in vitro and in vivo approaches. The receptor, PxutGr1, responds specifically to synephrine in Sf9 cells. The sensitivity of tarsal taste sensilla to synephrine and the oviposition behaviour in response to synephrine are strongly reduced after injecting double-stranded RNA of PxutGr1 into pupae. These observations indicate that the receptor PxutGr1 represents a key factor in host specialization in P. xuthus. PMID- 22086343 TI - Wide-band quantum interface for visible-to-telecommunication wavelength conversion. AB - Although near-infrared photons in telecommunication bands are required for long distance quantum communication, various quantum information tasks have been performed by using visible photons for the past two decades. Recently, such visible photons from diverse media including atomic quantum memories have also been studied. Optical frequency down-conversion from visible to telecommunication bands while keeping the quantum states is thus required for bridging such wavelength gaps. Here we report demonstration of a quantum interface of frequency down-conversion from visible to telecommunication bands by using a nonlinear crystal, which has a potential to work over wide bandwidths, leading to a high speed interface of frequency conversion. We achieved the conversion of a picosecond visible photon at 780 nm to a 1,522-nm photon, and observed that the conversion process retained entanglement between the down-converted photon and another photon. PMID- 22086344 TI - Initiation of statin therapy: are there age limits? AB - Cardiovascular disease (CVD) is the leading cause of death, with a higher prevalence in older adults who form an increasing proportion of the population of the United States. Statin treatment reduces cardiovascular morbidity and mortality in middle-aged adults. However, few studies have included older individuals, particularly ages 80 years or older. We review recent publications regarding primary and secondary prevention of CVD with statin therapy in older adults. Risk scores and their limitations in this population are discussed. The association of adverse effects with intensive doses of statin and their interactions with other drugs may be more problematic in older adults. Statin therapy appears cost-effective for individuals with higher CVD risk but this is dependent on the assumptions used. Evidence remains limited regarding the overall benefit of starting statin therapy in adults ages 80 years and older; thus, clinical judgment remains necessary in making this decision. PMID- 22086346 TI - Cost-effectiveness analysis of polymyxin-B immobilized fiber column and conventional medical therapy in the management of abdominal septic shock in Italy. AB - INTRODUCTION: Severe abdominal sepsis and septic shock are common problems in intensive care units (ICUs), and carry high mortality. The purpose of this economic analysis was to determine the cost-effectiveness of polymyxin B immobilized fiber column (PMX-F) plus conventional therapy (CT) (PMX-F-CT) versus CT alone for patients with severe sepsis/septic shock of abdominal origin, in the perspective of the Italian hospital. METHODS: This was a retrospective cost effectiveness analysis (CEA) based on data of clinical efficacy and consumption of resources collected alongside an Italian randomized clinical trial. 64 patients were enrolled following emergency surgery for intra-abdominal infection in 10 tertiary care ICUs from December 2004 to December 2007. Direct medical costs analyzed in the study included the consumption of hospital days, ICU days, catecholamine treatment days, renal replacement therapy days, mechanical ventilation treatment days, and the use of the PMX-F device. Resources were valued using published 2010 tariffs and market values. All-cause hospital mortality was extrapolated to survival as expected life years (LY) per patient/arm: for each survivor, average age-gender-related years of life expectancy were retrieved from national life tables; for deceased patients, only the number of CRF reported survival days was retained. Baseline expected years of survival were weighed by the severity of sepsis, according to individual Acute Physiology and Chronic Health Evaluation (Apache) II scores, showing that age/disease severity were comparable in the two groups before treatment initiation. Life expectancy per patient in each treatment group was thus calculated as the combination of life expectancy from Italian National Statistics Institute life tables and intra-hospital mortality detected in the Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock (EUPHAS) study. After all costs and 3% discounted survival years were calculated per patient per treatment arm, the incremental CEA was run to obtain the incremental cost-effectiveness ratio (ICER). Univariate sensitivity analyses and 2,000 bootstrap replications were run to test the robustness of the study results. RESULTS: Based on the expected survival years (mean discounted PMX-F-CT 9.37 LY/patient, CT 4.92 LY/patient; difference for PMX-F-CT 4.45 LY/patient; mean undiscounted PMX-F-CT 13.92 LY/patient, CT 7.19 LY/patient; difference +6.73 LY/patient), and the expected mean cost (PMX-F-CT mean 59,922 EUR/patient, CT mean 42,712 EUR/patient; difference for PMX-F-CT 17,211 EUR/patient), the mean ICER for PMX- F-CT resulted in 3,864 EUR/life year gained (LYG; ICER 2,558/undiscounted LYG). Results of the base-case CEA were confirmed by all sensitivity analyses, with ICER values always well below commonly accepted value thresholds. CONCLUSION: PMX-F-CT versus CT is a cost-effective intervention for treatment of severe sepsis/septic shock of abdominal origin and could be considered for use in the Italian National Health System hospital setting. PMID- 22086345 TI - Understanding renal posttransplantation anemia in the pediatric population. AB - Advances in renal transplantation management have proven to be beneficial in improving graft and patient survival. One of the properties of a well-functioning renal allograft is the secretion of adequate amounts of the hormone erythropoietin to stimulate erythropoiesis. Posttransplantation anemia (PTA) may occur at any point in time following transplantation, and the cause is multifactoral. Much of our understanding of PTA is based on studies of adult transplant recipients. The limited number of studies that have been reported on pediatric renal transplant patients appear to indicate that PTA is prevalent in this patient population. Erythropoietin deficiency or resistance is commonly associated with iron deficiency. An understanding of the risk factors, pathophysiology and management of PTA in the pediatric renal transplant population may provide guidelines for clinicians and researchers in the pursuit of larger prospective randomized control studies aimed at improving our limited knowledge of PTA. Recognition of PTA through regular screening and evaluation of the multiple factors that may contribute to its development are recommended after transplantation. PMID- 22086347 TI - Enhancement of beta-carotene production by over-expression of HMG-CoA reductase coupled with addition of ergosterol biosynthesis inhibitors in recombinant Saccharomyces cerevisiae. AB - In this study, the synergistic effect of overexpressing the 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase gene and adding ergosterol synthesis inhibitor, ketoconazole, on beta-carotene production in the recombinant Saccharomyces cerevisiae was investigated. The results showed that the over expression of HMG-CoA reductase gene and adding 100 mg/l ketoconazole alone can result in 135.1 and 15.6% increment of beta-carotene concentration compared with that of the control (2.05 mg/g dry weight of cells), respectively. However, the combination of overexpressing HMG-CoA reductase gene and adding ketoconazole can achieve a 206.8% increment of pigment content (6.29 mg/g dry weight of cells) compared with that of the control. Due to the fact that over-expression of the HMG-CoA reductase gene can simultaneously improve the flux of the sterol and carotenoid biosynthetic pathway, it can be concluded that under the circumstances of blocking sterol biosynthesis, increasing the activity of HMG-CoA reductase can result in more precursors FPP fluxing into carotenoid branch and obtain a high increment of beta-carotene production. The results of this study collectively suggest that the combination of overexpressing HMG-CoA reductase gene and supplying ergosterol synthesis inhibitor is an effective strategy to improve the production of desirable isoprenoid compounds such as carotenoids. PMID- 22086349 TI - Resorcin[4]arene-derived mono-, bis- and tetra-imidazolium salts as ligand precursors for Suzuki-Miyaura cross-coupling. AB - Eleven resorcinarene cavitands bearing either one, two or four (3-R-1 imidazolylium)-methyl substituents (R = (n)Bu, Ph, Mes, (i)Pr(2)C(6)H(3)) anchored at resorcinolic "ortho" positions have been synthesised from the appropriate bromomethylated precursor. Combining the imidazolium salts with palladium acetate and Cs(2)CO(3) gave active Suzuki-Miyaura cross coupling catalysts. The highest activities were observed with the doubly functionalised cavitands, which all have the imidazolylium groups attached to proximal resorcinol units. PMID- 22086350 TI - Promoter methylation of the bone morphogenetic protein 6 gene in multiple myeloma. AB - Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-beta superfamily, are multifunctional signaling molecules that have become of increasing interest in cancer research. Recent observations suggest that alterations in BMPs and BMP signaling are associated with tumorigenesis and disease progression in various types of malignancies. This study investigated the methylation status of the BMP6 gene promoter in various types of plasma cell proliferative disorders by combined bisulfite restriction analysis. While BMP6 methylation was not detected in any samples from monoclonal gammopathies of undetermined significance, intramedullary multiple myeloma (MM), plasma cell leukemia or solitary plasmacytoma, both case studies and cell line studies showed that multiple extramedullary plasmacytoma (MEP) consistently carried a methylated BMP6 promoter. The BMP6 methylation-positive MEP was an aggressive form of MM with extremely high levels of serum lactate dehydrogenase (LDH). Bisulfite sequencing analysis confirmed intensive methylation at CpG sites of the BMP6 promoter region. The methylation of BMP6 was correlated with decreased levels of mRNA transcripts. Expression of BMP6 was restored by the demethylating agent 5 aza-2'-deoxycytidine, suggesting that the methylation is associated with transcriptional silencing. Our study implied that BMP6 promoter methylation is not a common event in MMs, but occurs in aggressive MEP. These findings warrant further investigation to clarify whether BMP6 methylation together with elevated LDH could be a marker of poor prognosis in MEP patients who should be considered for early intensive treatment. PMID- 22086352 TI - Grounding compositional symbols: no composition without discrimination. AB - The classical computational conception of meaning has been challenged by the idea that symbols must be grounded on sensorimotor processes. A difficult question arises from the fact that grounding representations cannot be symbolic themselves but, in order to support compositionality, should work as primitives. This implies that they should be precisely identifiable and strictly connected with discriminable perceptual features. Ideally, each representation should correspond to a single discriminable feature. The present study was aimed at exploring whether feature discrimination is a fundamental requisite for grounding compositional symbols. We studied this problem by using Integral stimuli, composed of two interacting and not separable features. Such stimuli were selected in Experiment 1 as pictures whose component features are easily or barely discriminable (Separable or Integral) on the basis of psychological distance metrics (City-block or Euclidean) computed from similarity judgments. In Experiment 2, either each feature was associated with one word of a two-word expression, or the whole stimulus with a single word. In Experiment 3, the procedure was reversed and words or expressions were associated with whole pictures or separate features. Results support the hypothesis that single words are best grounded by Integral stimuli and composite expressions by Separable stimuli, where a strict association of single words with discriminated features is possible. PMID- 22086351 TI - Cognitive architecture of perceptual organization: from neurons to gnosons. AB - What, if anything, is cognitive architecture and how is it implemented in neural architecture? Focusing on perceptual organization, this question is addressed by way of a pluralist approach which, supported by metatheoretical considerations, combines complementary insights from representational, connectionist, and dynamic systems approaches to cognition. This pluralist approach starts from a representationally inspired model which implements the intertwined but functionally distinguishable subprocesses of feedforward feature encoding, horizontal feature binding, and recurrent feature selection. As sustained by a review of neuroscientific evidence, these are the subprocesses that are believed to take place in the visual hierarchy in the brain. Furthermore, the model employs a special form of processing, called transparallel processing, whose neural signature is proposed to be gamma-band synchronization in transient horizontal neural assemblies. In neuroscience, such assemblies are believed to mediate binding of similar features. Their formal counterparts in the model are special input-dependent distributed representations, called hyperstrings, which allow many similar features to be processed in a transparallel fashion, that is, simultaneously as if only one feature were concerned. This form of processing does justice to both the high combinatorial capacity and the high speed of the perceptual organization process. A naturally following proposal is that those temporarily synchronized neural assemblies are "gnosons", that is, constituents of flexible self-organizing cognitive architecture in between the relatively rigid level of neurons and the still elusive level of consciousness. PMID- 22086353 TI - Caloric restriction modifies both innate and adaptive immunity in the mouse small intestine. AB - Although caloric restriction (CR) apparently has beneficial effects on the immune system, its effects on the immunological function of the intestinal mucosa are little known. The present study explored the effect of CR on the innate and adaptive intestinal immunity of mice. Balb/c mice were either fed ad libitum (control) or on alternate days fed ad libitum and fasted (caloric restriction). After 4 months, an evaluation was made of IgA levels in the ileum, the gene expression for IgA and its receptor (pIgR), as well as the expression of two antimicrobial enzymes (lysozyme and phospholipase A2) and several cytokines of the intestinal mucosa. CR increased the gene expression of lysozyme and phospholipase A2. The levels of IgA were diminished in the ileum, which apparently was a consequence of the reduced transport of IgA by pIgR. In ileum, CR increased the gene expression for most cytokines, both pro- and anti inflammatory. Hence, CR differentially modified the expression of innate and adaptive immunity mediators in the intestine. PMID- 22086354 TI - Construction of an extended library of adult male 3D models: rationale and results. AB - In order to best cover the possible extent of heights and weights of male adults the construction of 25 whole body 3D models has been undertaken. Such a library is thought to be useful to specify the uncertainties and relevance of dosimetry calculations carried out with models representing individuals of average body heights and weights. Representative 3D models of Caucasian body types are selected in a commercial database according to their height and weight, and 3D models of the skeleton and internal organs are designed using another commercial dataset. A review of the literature enabled one to fix volume or mass target values for the skeleton, soft organs, skin and fat content of the selected individuals. The composition of the remainder tissue is fixed so that the weight of the voxel models equals the weight of the selected individuals. After mesh and NURBS modelling, volume adjustment of the selected body shapes and additional voxel-based work, 25 voxel models with 109 identified organs or tissue are obtained. Radiation transport calculations are carried out with some of the developed models to illustrate potential uses. The following points are discussed throughout this paper: justification of the fixed or obtained models' features regarding available and relevant literature data; workflow and strategy for major modelling steps; advantages and drawbacks of the obtained library as compared with other works. The construction hypotheses are explained and justified in detail since future calculation results obtained with this library will depend on them. PMID- 22086355 TI - A novel structural form of MIL-53 observed for the scandium analogue and its response to temperature variation and CO2 adsorption. AB - The scandium analogue of the flexible terephthalate MIL-53 yields a novel closed pore structure upon removal of guest molecules which has unusual thermal behaviour and stepwise opening during CO(2) adsorption. By contrast, the nitro functionalised MIL-53(Sc) cannot fully close and the structure possesses permanent porosity for CO(2). PMID- 22086356 TI - Gut pH as a limiting factor for digestive proteolysis in cultured juveniles of the gilthead sea bream (Sparus aurata). AB - After the development of the gastric function in juvenile fish, dietary proteins enter a two-phase digestive process comprising an acidic gastric phase followed by an alkaline intestinal phase. However, the main gastric protease, pepsin, is strictly dependent on the existence of a low-enough environmental pH. In 20-g gilthead sea bream, Sparus aurata, the mean minimal gastric pH is close to 4.5, while the mean pH in the duodenal portion of the intestine was nearly fixed at 6.5. The mean maximal gastric content of HCl was approximately 20 microEq for a low-buffering diet. Gastric proteases were more severely affected than intestinal proteases when assayed at actual sub-optimal pH values, 4.5 and 6.5, respectively. When the gastric proteases of juvenile fish were pre-incubated with a citric acid buffer at pH 6.0, the activity at pH 4.5 was very low, whereas when they were pre-incubated with the same buffer at pH 3.0, the activity at pH 4.5 was significantly increased; this fact suggests a deficient activation of zymogens during the gastric digestion and points to a potential approach to improve protein digestion in juvenile gilthead sea bream. PMID- 22086357 TI - A comparison of approaches to control for confounding factors by regression models. AB - A common technique to control for confounding factors in practice is by regression adjustment. There are various versions of regression modeling in the literature, and in this paper we considered four approaches often seen in genetic association studies. We carried out both analytical and simulation studies comparing the bias of effect size estimates and examining the test sizes under the null hypothesis of no association between an outcome and an exposure. Further, we compared the methods in a nonsynonymous genome-wide scan for plasma lipoprotein(a) levels using a dataset from the Dallas Heart Study. We found that a widely employed approach that models the covariate-adjusted outcome and the exposure leads to an infranominal test size and underestimation of the exposure effect size. In conclusion, we recommend either using multiple regression models or modeling the covariate-adjusted outcome and the covariate-adjusted exposure to control for confounding factors. PMID- 22086358 TI - Central angiotensin I increases swallowing activity and oxytocin release in the near-term ovine fetus. AB - The brain renin-angiotensin system (RAS) plays an important role in hydromineral and neuroendocrine balance. Although previous studies showed that exogenous angiotensin (Ang) II increased dipsogenic and vasopressin responses in near-term fetuses, little is known about the functional development of fetal endogenous brain RAS in the regulation of body fluid homeostasis. To determine the functional development of the central angiotensin-converting enzyme (ACE) in utero, we investigated the electrocortical (ECoG) activity, swallowing activity, oxytocin (OT) release, and c-fos expression in response to intracerebroventricular Ang I administration in the near-term fetal lamb. Ang I did not change fetal low-voltage (LV) and high-voltage (HV) ECoG temporal distributions, but increased fetal swallowing activity during LV ECoG (1.0+/-0.1 to 3.5+/-0.4 swallows/min). Additionally, Ang I evoked an increase in c-fos immunoreactivity in putative dipsogenic centers, including the supraoptic and paraventricular nuclei of the hypothalamus, accompanied by an increase in fetal plasma OT levels. The expression of c-fos was demonstrated in OT neurons in the hypothalamus. The Ang I-mediated increase in fetal swallowing and plasma OT was inhibited by captopril. These results demonstrate the functional development of the fetal brain ACE system in the last trimester of gestation, which plays an important role in the RAS-mediated dipsogenic response and OT release in the regulation of body fluid homeostasis. PMID- 22086359 TI - CREB involvement in the regulation of striatal prodynorphin by nicotine. AB - RATIONALE: The transcription factor cAMP response element binding (CREB) protein plays a pivotal role in drug-dependent neuronal plasticity. CREB phosphorylation at Ser133 is enhanced by drugs of abuse, including nicotine. Dynorphin (Dyn) contributes to the addictive process and its precursor gene prodynorphin (PD) is regulated by CREB. PD mRNA and Dyn synthesis were enhanced in the striatum following acute nicotine, suggesting genomic regulation. OBJECTIVE: These studies investigated PD transcription in mice acutely treated with nicotine, determined the role of CREB, and characterized the receptors involved. RESULTS: Acute nicotine increased adenylyl cyclase activity, cAMP, and pCREB Ser133 levels in striatum and enhanced CREB binding to CRE elements (DynCREs) of the PD promoter, preferentially DynCRE3. DynCRE3 binding was dose dependent with 1 mg of nicotine giving a maximal response. Additionally, DynCRE binding was time dependent, rising by 15 min, reaching a maximum at 1 h, and returning to control by 3 h, a temporal pattern similar to that of cAMP and pCREB. Supershift experiments showed that CREB and pCREB Ser133 were the major contributors to DynCRE3 binding complex. The nAChR antagonist mecamylamine and the dopamine D1-like receptor antagonist SCH 23390 prevented the nicotine-induced increase of pCREB and nuclear protein binding to DynCRE3. CONCLUSIONS: Our findings suggest that nicotine regulates PD expression in striatum at the transcriptional level and CREB is involved. Dopamine D1 receptor stimulation by nAChR-released dopamine appears to be an underlying mechanism. Altered Dyn synthesis might be relevant for the behavioral actions of nicotine and especially its aversive properties. PMID- 22086360 TI - Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats. AB - RATIONALE: Methylphenidate is a psychostimulant given for extended periods of time as a treatment of attention-deficit/hyperactivity disorder (ADHD). The long term effects of the drug are not yet known, and it is speculated that repeated exposure may produce drug dependence. OBJECTIVE: To investigate the effects of repeated methylphenidate treatment on methylphenidate self-administration and reinstatement in the most validated animal model of ADHD, the spontaneously hypertensive rat (SHR), and Wistar rat, strain representing the "normal" heterogeneous population. METHODS: Rats were administered intraperitoneally with saline or methylphenidate (2 mg/kg) for 14 days, prior to experiments. Thereafter, responses for intravenous methylphenidate under the fixed ratio (FR1 and FR3) and progressive ratio (PR) schedules were assessed. Extinction experiments followed, as well as tests to determine the ability of intraperitoneal administration of methylphenidate (2 and 5 mg/kg) to reinstate extinguished drug-seeking behaviors in rats. RESULTS: Previous exposure to methylphenidate enhanced methylphenidate self-administration in Wistar rats but not in SHR (FR3). Methylphenidate pretreatment reduced responding for methylphenidate in SHR but did not affect self-administration behaviors of Wistar rats (PR). Methylphenidate pre-exposure robustly reinstated drug-seeking behaviors in Wistar rats, but not in SHR. CONCLUSION: The contrasting effects of repeated methylphenidate treatment in methylphenidate self-administration and reinstatement in Wistar and SHR, and the increased susceptibility of the Wistar rat strain to the reinforcing effects of methylphenidate indicate that "normal" individuals are more likely to develop psychological dependence to the drug and experience relapse. Meanwhile, the clinical use of methylphenidate may not produce drug dependence or relapse in ADHD patients. PMID- 22086362 TI - The quality of work life of people with severe mental disorders working in social enterprises: a qualitative study. AB - PURPOSE: The aim of this phenomenological study is to provide an in-depth understanding of the meaning that people with severe mental disorders give about their quality of work life (QWL) while working in social enterprises. METHODS: Semi-structured interviews with 14 participants were conducted. All interviews were recorded and transcribed verbatim. Colaizzi's framework for data analysis was used. RESULTS: Eight sub-themes emerged and can be better understood within two larger themes: (A) interpersonal and intrapersonal aspects of QWL and (B) structural and physical aspects. Within theme A, sub-themes were (1) having a sense of belonging to the enterprise, (2) having the feeling of being a good worker, (3) establishing relationships with co-workers, and (4) establishing relationships with supervisors. Within theme B, sub-themes were (5) working tasks, (6) working conditions, (7) working environment, and (8) organizational management. CONCLUSIONS: The findings highlight the importance of understanding the perspective of people with severe mental disorders regarding their QWL in order to better tailor interventions that enhance it. Although some sub-themes of QWL identified in the present study were similar to those found in previous studies conducted with other populations, a unique sub-theme of QWL was identified: having the feeling of being a good worker. Specific QWL measurement that addresses this unique sub-theme is needed when assessing QWL of people with severe mental disorders. PMID- 22086363 TI - Management of hyperglycemia during the perioperative period. AB - Hyperglycemia is frequently encountered in the inpatient setting and is distinctly associated with poor clinical outcomes. Recent literature suggests an association between stringent glycemic control and increased mortality, thus keeping optimal glycemic targets a relevant subject of debate. In the surgical population, hyperglycemia with or without diabetes mellitus may be unrecognized. Factors contributing to hyperglycemia in the hospital include critical illness, use of certain drugs, use of enteral or parenteral nutrition, and variability in oral or nutritional intake as can occur when patients are prepared for procedures or surgery. A sensible approach to managing hyperglycemia in this population includes preoperative recognition of diabetes mellitus and risks for inpatient hyperglycemia. Judicious control of glycemia during the pre-, intra-, and postoperative time periods with avoidance of hypoglycemia mandates the need for a strategy for patient management that extend to time of discharge. We review the consequences of uncontrolled perioperative hyperglycemia, discuss current clinical guidelines and recent controversies, and provide practical tools for glycemic control in the surgical population. PMID- 22086361 TI - The association of tooth loss with all-cause and circulatory mortality. Is there a benefit of replaced teeth? A systematic review and meta-analysis. AB - We systematically reviewed whether the number of teeth is related to all-cause or circulatory mortality and whether replaced teeth are protective against all-cause or circulatory mortality. The search was based on the PubMed database. All cohort studies published in peer-reviewed journals were selected. Studies on periodontal disease and mortality were excluded if they did not provide information on the number of teeth. Risk estimates from studies with appropriate exposure definition, confounder adjustment and sample size were included in a meta analysis. Three high-quality studies found a relationship between the number of teeth and circulatory mortality, whereas a moderate study did not. Two out of four moderate- to high-quality studies reported a relationship between the number of teeth and all-cause mortality. No study has investigated whether replaced teeth are protective against mortality. Therefore, denture use was taken as proxy. The methodological quality of studies on denture use and mortality was generally low to moderate. The findings of two moderate studies indicated an effect of prosthodontic replacements on all-cause mortality, which was supported in bias analysis. It is open whether competing risks of cause-specific death other than circulatory mortality reduce an effect of the number of teeth on all cause mortality. An effect of denture use on circulatory mortality remains to be established, as well as whether the number of replaced teeth affects mortality. Specifying the role of potential pathways by which tooth loss-related mortality is mediated will possibly increase the value of dental treatment for general health. PMID- 22086364 TI - Oral ingestion of Lentinula edodes mycelia extract can restore the antitumor T cell response of mice inoculated with colon-26 cells into the subserosal space of the cecum. AB - We previously reported that oral ingestion of Lentinula edodes mycelia (L.E.M.) extract can inhibit the growth of a subcutaneously established melanoma in a T cell-dependent manner via mitigation of regulatory T cell (Treg)-mediated immunosuppression. In this study, we tested the antitumor effect and mechanism of oral ingestion of L.E.M. extract following inoculation of murine colon carcinoma colon-26 (C26) cells into the subserosal space of the cecum (i.c.) of syngeneic mice. In this model, the primary site of the immune response was gut-associated lymphoid tissue (GALT), which is known to be an immunological tolerance-inducing site for numerous dietary antigens. Oral ingestion of the L.E.M. extract suppressed the growth of i.c.-inoculated C26 cells in a T cell-dependent manner and restored the T cell response of the mesenteric lymph nodes and the spleen, not only to a tumor antigen-derived peptide, presented on H-2Ld molecules, but also to C26 cells. I.c. inoculation of C26 cells increased the potential of CD4+ T cells of the mesenteric lymph nodes to produce transforming growth factor (TGF) beta, but ingestion of the L.E.M. extract decreased the ability of both CD4+ and CD8+ T cells in the mesenteric lymph nodes to produce this immunosuppressive cytokine. Although ingestion of L.E.M. showed only a marginal effect on Tregs in this model, this treatment significantly reduced the plasma levels of TGF-beta and IL-6, both of which were increased in the i.c. C26-inoculated mice. In summary, our results indicate that oral ingestion of L.E.M. extract can restore antitumor T cell responses of mice even when the primary antitumor immune response is elicited in GALT, and provide important implications for anticancer immunotherapy of human colon cancer. PMID- 22086365 TI - Immunoadsorption therapy for steroid-unresponsive relapses in patients with multiple sclerosis. AB - BACKGROUND: Therapeutic plasma exchange (TPE) in steroid-unresponsive relapses of patients with multiple sclerosis (MS) is an established therapy with response rates of up to 70%. Immunoadsorption (IA) specifically removes immunoglobulins from the patient's plasma. It is hypothesized that IA therapy might be better tolerated than and as effective as TPE in the treatment of MS relapses. Experiences with IA therapy of steroid-unresponsive MS relapses are limited. METHODS: We report our experiences with IA therapy in a series of 10 patients with steroid-unresponsive MS relapses. RESULTS: A marked to moderate clinical response with clear gain of function was observed in 66% of our patients. IA therapy was well tolerated. CONCLUSIONS: IA therapy is an effective and well tolerated therapeutic option for steroid-unresponsive MS relapses. PMID- 22086366 TI - Reversing invasion in bistable systems. AB - In this paper, we discuss a class of bistable reaction-diffusion systems used to model the competitive interaction of two species. The interactions are assumed to be of classic "Lotka-Volterra" type and we will consider a particular problem with relevance to applications in population dynamics: essentially, we study under what conditions the interplay of relative motility (diffusion) and competitive strength can cause waves of invasion to be halted and reversed. By establishing rigorous results concerning related degenerate and near-degenerate systems, we build a picture of the dependence of the wave speed on system parameters. Our results lead us to conjecture that this class of competition model has three "zones of response". In the central zone, varying the motility can slow, halt and reverse invasion. However, in the two outer zones, the direction of invasion is independent of the relative motility and is entirely determined by the relative competitive strengths. Furthermore, we conjecture that for a large class of competition models of the type studied here, the wave speed is an increasing function of the relative motility. PMID- 22086367 TI - A method to derive vegetation distribution maps for pollen dispersion models using birch as an example. AB - Detailed knowledge of the spatial distribution of sources is a crucial prerequisite for the application of pollen dispersion models such as, for example, COSMO-ART (COnsortium for Small-scale MOdeling-Aerosols and Reactive Trace gases). However, this input is not available for the allergy-relevant species such as hazel, alder, birch, grass or ragweed. Hence, plant distribution datasets need to be derived from suitable sources. We present an approach to produce such a dataset from existing sources using birch as an example. The basic idea is to construct a birch dataset using a region with good data coverage for calibration and then to extrapolate this relationship to a larger area by using land use classes. We use the Swiss forest inventory (1 km resolution) in combination with a 74-category land use dataset that covers the non-forested areas of Switzerland as well (resolution 100 m). Then we assign birch density categories of 0%, 0.1%, 0.5% and 2.5% to each of the 74 land use categories. The combination of this derived dataset with the birch distribution from the forest inventory yields a fairly accurate birch distribution encompassing entire Switzerland. The land use categories of the Global Land Cover 2000 (GLC2000; Global Land Cover 2000 database, 2003, European Commission, Joint Research Centre; resolution 1 km) are then calibrated with the Swiss dataset in order to derive a Europe-wide birch distribution dataset and aggregated onto the 7 km COSMO-ART grid. This procedure thus assumes that a certain GLC2000 land use category has the same birch density wherever it may occur in Europe. In order to reduce the strict application of this crucial assumption, the birch density distribution as obtained from the previous steps is weighted using the mean Seasonal Pollen Index (SPI; yearly sums of daily pollen concentrations). For future improvement, region-specific birch densities for the GLC2000 categories could be integrated into the mapping procedure. PMID- 22086368 TI - Development: autophagy eliminates paternal mitochondria. PMID- 22086370 TI - Cell cycle: E2F1 ensures the endocycle. PMID- 22086372 TI - Photocurrent enhancement tuned with plasmonic resonance in self-assembled monolayers fabricated on regularly arrayed gold nanostructures. AB - We investigated the enhancement properties of the photocurrent generation from self-assembled monolayers of porphyrin fabricated on periodic structures of gold half-shells. Tuning the surface plasmon frequency of the nanostructures led to correlated wavelength dependences of the external quantum efficiencies of the photocurrents, as well as fluorescence intensities resulting from effective electronic excitation of porphyrin molecules. PMID- 22086371 TI - Tail-anchored membrane protein insertion into the endoplasmic reticulum. AB - Membrane proteins are inserted into the endoplasmic reticulum (ER) by two highly conserved parallel pathways. The well-studied co-translational pathway uses signal recognition particle (SRP) and its receptor for targeting and the SEC61 translocon for membrane integration. A recently discovered post-translational pathway uses an entirely different set of factors involving transmembrane domain (TMD)-selective cytosolic chaperones and an accompanying receptor at the ER. Elucidation of the structural and mechanistic basis of this post-translational membrane protein insertion pathway highlights general principles shared between the two pathways and key distinctions unique to each. PMID- 22086369 TI - Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. AB - Half a century of biochemical and biophysical experiments has provided attractive models that may explain the diverse functions of microtubules within cells and organisms. However, the notion of functionally distinct microtubule types has not been explored with similar intensity, mostly because mechanisms for generating divergent microtubule species were not yet known. Cells generate distinct microtubule subtypes through expression of different tubulin isotypes and through post-translational modifications, such as detyrosination and further cleavage to Delta2-tubulin, acetylation, polyglutamylation and polyglycylation. The recent discovery of enzymes responsible for many tubulin post-translational modifications has enabled functional studies demonstrating that these post translational modifications may regulate microtubule functions through an amazing range of mechanisms. PMID- 22086373 TI - Exploring the role of miRNAs in renal cell carcinoma progression and metastasis through bioinformatic and experimental analyses. AB - Metastasis results in most of the cancer deaths in clear cell renal cell carcinoma (ccRCC). MicroRNAs (miRNAs) regulate many important cell functions and play important roles in tumor development, metastasis and progression. In our previous study, we identified a miRNA signature for metastatic RCC. In this study, we validated the top differentially expressed miRNAs on matched primary and metastatic ccRCC pairs by quantitative polymerase chain reaction. We performed bioinformatics analyses including target prediction and combinatorial analysis of previously reported miRNAs involved in tumour progression and metastasis. We also examined the co-expression of the miRNAs clusters and compared expression of intronic miRNAs and their host genes. We observed significant dysregulation between primary and metastatic tumours from the same patient. This indicates that, at least in part, the metastatic signature develops gradually during tumour progression. We identified metastasis-dysregulated miRNAs that can target a number of genes previously found to be involved in metastasis of kidney cancer as well as other malignancies. In addition, we found a negative correlation of expression of miR-126 and its target vascular endothelial growth factor (VEGF)-A. Cluster analysis showed that members of the same miRNA cluster follow the same expression pattern, suggesting the presence of a locus control regulation. We also observed a positive correlation of expression between intronic miRNAs and their host genes, thus revealing another potential control mechanism for miRNAs. Many of the significantly dysregulated miRNAs in metastatic ccRCC are highly conserved among species. Our analysis suggests that miRNAs are involved in ccRCC metastasis and may represent potential biomarkers. PMID- 22086375 TI - H-bonding and steric effects on the properties of phenolate and phenoxyl radical complexes of Cu(II). AB - Herein, the N-R substituted N,O-phenol-pyrazole redox-active pro-ligands, (R)LH (R = Me, Pr) are reported together with their corresponding bis-Cu(R)L(2) complexes (2 and 3, respectively). The latter are reversibly oxidised to the corresponding stable Cu(II)-phenoxyl radical complexes 2(+) and 3(+). The properties of the tetrahedrally distorted complexes 2 and 3 (and those of 2(+) and 3(+)) are being compared to those of the square-planar H-bonded complex 1 (bis-Cu(H)L(2)) and those of 1(+). These studies have permitted H-bonding and steric effects on the redox, spectroscopic and chemical properties of Cu(II) phenolate and Cu(II)-phenoxyl radical species to be established. PMID- 22086374 TI - Isolation and characterization of a new repetitive DNA family recently amplified in the Mesoamerican gene pool of the common bean (Phaseolus vulgaris L., Fabaceae). AB - The common bean (Phaseolus vulgaris) is one of the most important crop plants. About 50% of its genome is composed of repetitive sequences, but only a little fraction was isolated and characterized so far. In this paper, a new repetitive DNA family from the species, named PvMeso, was isolated and characterized in both gene pools of P. vulgaris (Andean and Mesoamerican) and related species. Two fragments, 1.7 and 2.3 kb long, were cloned from BAC 255F18, which has previously shown a repetitive pattern. The subclone PvMeso-31 showed a terminal block in chromosome 7. This subclone contains a 1,705 bp long, AT-rich repeat with small internal repeats and shares a 1.2 kb region with PvMeso-47, derived from the 2.3 kb fragment. The presence of this repetitive block was restricted to Mesoamerican accessions of the common bean. In P. acutifolius, P. leptostachyus and Andean P. vulgaris, only a faint, 2.3 kb fragment was visualized in Southern experiments. Moreover, in Mesoamerican accessions, two other fragments (1.7 kb and 3.4 kb) were strongly labelled as well. Taken together, our results indicate that PvMeso is a recently emerged, repeat family initially duplicated in chromosome 11, on ancestral Mesoamerican accession, and later amplified in chromosome 7, after the split of the two major gene pools of the common bean. PMID- 22086376 TI - [Discontinuing oral anticoagulation for elective surgical interventions]. PMID- 22086377 TI - [A lucky find. 1932]. PMID- 22086378 TI - [The medical emergency department in a Swiss regional hospital: the important role of generalists]. AB - Patients not having a general practitioner will more likely use the emergency departments (ED) of hospitals for primary care. Crowding of the ED due to patients with minor health problems is a growing burden. The present work was aimed to analyze data of ED consultations at a Swiss regional hospital. Leading diagnoses of ED consultations covered a broad spectrum of internal medicine. The majority of patients seen in the ED are "walk-in" patients with minor problems that after initial evaluation and treatment in the ED could be managed as outpatients. Pediatric patients made a considerable part of the workload. Elderly patients (>65 years) were hospitalized more often. PMID- 22086379 TI - [Gallstone disease: basic mechanisms, diagnosis and therapy]. AB - Gallstone disease is one of the most common gastroenterological diseases and represents a major burden for our heath care systems. Cholesterol gallstones, responsible for about 90% of stones, represent a multifactorial disease with an important genetic component. Most gallstone-carriers remain asymptomatic and hence in general, they not need any therapy. In contrast those with symptomatic (biliary colic) or complicated gallstone disease (cholecystitis, obstructive cholangitis, biliary pancreatitis) have to be treated interdisciplinary by surgeons and endoscopists. Laparoscopic cholecystectomy represents the causal therapy to avoid recurrent symptoms as well as the therapy of choice for cholecystitis as the most common complication of gallstone disease. Bile duct stones and the associated complications (cholangitis, biliary pancreatitis) are primarily treated endoscopically. PMID- 22086380 TI - [Topical therapy of ulcerative colitis]. AB - The availability of new topical preparations for the treatment of left sided ulcerative colitis ulcerosa offers a therapy optimization for many patients. Rectal application of steroids and 5-aminosalicylic acid (5-ASA) is associated with fewer side effects and has a higher therapeutic efficacy in mild to moderate active left-sided colitis as compared to a systemic therapy. Often it is argued that the patients' compliance is insufficient with a rectal therapy. However, with sufficient information on the proven advantages this is usually not the case. The rectal application of drugs in distal ulcerative colitis is suitable also for the maintenance of remission. Therefore the new therapy guidelines recommend topical therapy more than in former times. Subsequently, these manuscripts focussed specifically on the topical therapy of distal colitis, to elucidate that clear treatment advantages are present in daily practice. PMID- 22086381 TI - [The tearing eye]. PMID- 22086382 TI - [Ambulatory treatment of patients with lung embolism]. PMID- 22086383 TI - [No difference in recurrence risk of venous thromboembolism treated with anticoagulation for 3 months or longer]. PMID- 22086385 TI - [Broad complex tachycardia of different morphologies. - CME ECG 35]. PMID- 22086388 TI - Bridging taxonomic and disciplinary divides in infectious disease. AB - Pathogens traverse disciplinary and taxonomic boundaries, yet infectious disease research occurs in many separate disciplines including plant pathology, veterinary and human medicine, and ecological and evolutionary sciences. These disciplines have different traditions, goals, and terminology, creating gaps in communication. Bridging these disciplinary and taxonomic gaps promises novel insights and important synergistic advances in control of infectious disease. An approach integrated across the plant-animal divide would advance our understanding of disease by quantifying critical processes including transmission, community interactions, pathogen evolution, and complexity at multiple spatial and temporal scales. These advances require more substantial investment in basic disease research. PMID- 22086390 TI - The effect of motion correction on pharmacokinetic parameter estimation in dynamic-contrast-enhanced MRI. AB - A dynamic-contrast-enhanced magnetic resonance imaging (DCE-MRI) dataset consists of many imaging frames, often acquired both before and after contrast injection. Due to the length of time spent acquiring images, patient motion is likely and image re-alignment or registration is required before further analysis such as pharmacokinetic model fitting. Non-rigid image registration procedures may be used to correct motion artefacts; however, a careful choice of registration strategy is required to reduce misregistration artefacts associated with enhancing features. This work investigates the effect of registration on the results of model-fitting algorithms for 52 DCE-MR mammography cases for 14 patients. Results are divided into two sections: a comparison of registration strategies in which a DCE-MRI-specific algorithm is preferred in 50% of cases, followed by an investigation of parameter changes with known applied deformations, inspecting the effect of magnitude and timing of motion artefacts. Increased motion magnitude correlates with increased model-fit residual and is seen to have a strong influence on the visibility of strongly enhancing features. Motion artefacts in images close to the contrast agent arrival have a disproportionate effect on discrepancies in parameter estimation. The choice of algorithm, magnitude of motion and timing of the motion are each shown to influence estimated pharmacokinetic parameters even when motion magnitude is small. PMID- 22086389 TI - The association of CD46, SLAM and CD209 cellular receptor gene SNPs with variations in measles vaccine-induced immune responses: a replication study and examination of novel polymorphisms. AB - BACKGROUND: The measles virus (MV) interacts with two known cellular receptors: CD46 and SLAM. The transmembrane receptor CD209 interacts with MV and augments dendritic cell infection. METHODS: 764 subjects previously immunized with measles mumps-rubella vaccine were genotyped for 66 candidate SNPs in the CD46, SLAM and CD209 genes as part of a larger study. RESULTS: A previously detected association of the CD46 SNP rs2724384 with measles-specific antibodies was successfully replicated in this study. Increased representation of the minor allele G for an intronic CD46 SNP was associated with an allele dose-related decrease (978 vs. 522 mIU/ml, p = 0.0007) in antibody levels. This polymorphism rs2724384 also demonstrated associations with IL-6 (p = 0.02), IFN-alpha (p = 0.007) and TNF alpha (p = 0.0007) responses. Two polymorphisms (coding rs164288 and intronic rs11265452) in the SLAM gene that were associated with measles antibody levels in our previous study were associated with IFN-gamma Elispot (p = 0.04) and IL-10 responses (p = 0.0008), respectively, in this study. We found associations between haplotypes, AACGGAATGGAAAG (p = 0.009) and GGCCGAGAGGAGAG (p < 0.001), in the CD46 gene and TNF-alpha secretion. CONCLUSION: Understanding the functional and mechanistic consequences of these genetic polymorphisms on immune response variations could assist in directing new measles and potentially other viral vaccine design, and in better understanding measles immunogenetics. PMID- 22086391 TI - Decoding overlapping memories in the medial temporal lobes using high-resolution fMRI. AB - The hippocampus is proposed to process overlapping episodes as discrete memory traces, although direct evidence for this in human episodic memory is scarce. Using green-screen technology we created four highly overlapping movies of everyday events. Participants were scanned using high-resolution fMRI while recalling the movies. Multivariate pattern analysis revealed that the hippocampus supported distinct representations of each memory, while neighboring regions did not, demonstrating that the human hippocampus maintains unique pattern-separated memory traces even when memories are highly overlapping. The hippocampus also contained representations of spatial contexts that were shared across different memories, consistent with a specialized role in processing space. PMID- 22086392 TI - The cellular mechanisms of memory are modified by experience. AB - The N-methyl-D-aspartate receptor (NMDAR) is thought to be essential for synaptic plasticity and learning. However, recent work indicates that the role of this receptor depends on the prior history of the research subject. For example, animals trained on a hippocampus-dependent learning task are subsequently able to acquire new information in the absence of NMDAR activation. The current experiments were designed to identify the types of experiences that lead to NMDAR independent learning. Using contextual fear conditioning in mice, we find that NMDAR-independent learning is only observed when (1) animals are trained on the same behavioral task and (2) initial learning is successfully encoded into long term memory. PMID- 22086393 TI - Anterior thalamic lesions alter both hippocampal-dependent behavior and hippocampal acetylcholine release in the rat. AB - The anterior thalamic nuclei (ATN) are important for learning and memory as damage to this region produces a persistent amnestic syndrome. Dense connections between the ATN and the hippocampus exist, and importantly, damage to the ATN can impair hippocampal functioning. Acetylcholine (ACh) is a key neurotransmitter in the hippocampus, and in vivo measures of ACh are correlated to learning and memory performance. In the present study, complete lesions of the ATN impaired performance on two measures of hippocampal-dependent learning and memory (spontaneous alternation and delayed alternation) and severely disrupted behaviorally evoked ACh efflux within the hippocampus of adult male rats. In contrast, incomplete ATN lesions did not impair spontaneous alternation performance but did impair delayed alternation performance while blunting hippocampal ACh efflux. Interestingly, ATN lesions of any size did not affect basal concentrations of ACh in the hippocampus. These results demonstrate that the ATN have the capacity to modulate behaviorally relevant neuronal transmission within the hippocampus. PMID- 22086394 TI - Efficient inhibition of an intraperitoneal xenograft model of human ovarian cancer by HSulf-1 gene delivered by biodegradable cationic heparin polyethyleneimine nanogels. AB - The HSulf-1 (heparan sulfate 6-O-endosulfatase 1) gene is an important element that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs), leading to the interference of HSPG-related signal transduction pathways. HSulf-1 plays a key role in regulating cell proliferation, tumorigenesis and angiogenesis. Recently, some studies have reported that HSulf-1 is a down regulated gene in the majority of examined tumor types. In our present study, a recombinant plasmid DNA carrying HSulf-1-cDNA (pHSulf-1) was constructed. The antitumor effect of pHSulf-1 delivered by heparin-polyethyleneimine (HPEI) nanogels on human ovarian cancer and the possible mechanisms of the antitumor efficacy in vivo were further investigated. Heparin-polyethyleneimine (HPEI) nanogels, as a new safe non-viral gene delivery carrier, were prepared to deliver the plasmid expressing HSulf-1 into HSulf-1-deficient SKOV3 human ovarian cancer cells in vitro and in vivo. pHSulf-1 could be efficiently transfected into SKOV3 ovarian cancer cells by HPEI nanogels in vitro and in vivo. Stable expression of HSulf-1 in vitro and in vivo was verified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Furthermore, a SKOV3 intraperitoneal ovarian carcinomatosis model was established to investigate the growth inhibition function of pHSulf-1 in nude mice. Tumor weight was measured. An anti-angiogenesis effect of pHSulf-1 in vivo was detected by CD31 immunostaining and alginate-encapsulate tumor cell assay. Assessment of apoptotic cells and proliferation index in tumor tissues were performed by TUNEL assay and Ki-67 immunostaining. Intraperitoneal injection of pHSulf-1/HPEI complexes efficiently reduced tumor weight by approximately 87% compared with control groups (P<0.01). Meanwhile, reduction in angiogenesis, inhibition of cell proliferation, as well as induction of tumor cell apoptosis were observed, without apparent systemic toxic effects. Collectively, these observations provide the first evidence that pHSulf-1 delivered by HPEI nanogels may become a promising therapeutic strategy against human ovarian cancer. PMID- 22086395 TI - Management of renal cell carcinoma in sigmoid kidney. AB - Crossed renal ectopia is a rare congenital malformation. We report a case in a 77 year-old man presenting with a left lower abdominal mass. Abdominal computed tomography showed a vascular lesion that developed in a right-to-left crossed fused renal ectopia. The patient was treated with radical heminephrectomy. Appropriate preoperative imaging and surgical technique for the isthmusectomy are highlighted. PMID- 22086396 TI - Gold nanoparticle fluorescent molecular beacon for low-resolution DQ2 gene HLA typing. AB - Coeliac disease is an inflammation of the small intestine triggered by gluten ingestion. We present a fluorescent genosensor, exploiting molecular-beacon functionalized gold nanoparticles, for the identification of human leukocyte antigen (HLA) DQ2 gene, a key genetic factor in coeliac disease. Optimization of sensor performance was achieved by tuning the composition of the oligonucleotide monolayer immobilized on the gold nanoparticle and the molecular beacon design. Co-immobilization of the molecular beacon with a spacing oligonucleotide (thiolated ten-thymine oligonucleotide) in the presence of ten-adenine oligonucleotides resulted in a significant increase of the sensor response owing to improved spacing of the molecular beacons and extension of the distance from the nanoparticle surface, which renders them more available for recognition. Further increase in the response (approximately 40%) was shown to be achievable when the recognition sequence of the molecular beacon was incorporated in the stem. Improvement of the specificity of the molecular beacons was also achieved by the incorporation within their recognition sequence of a one-base mismatch. Finally, gold nanoparticles functionalized with two molecular beacons targeting the DQA1*05* and DQB1*02* alleles allowed the low-resolution typing of the DQ2 gene at the nanomolar level. PMID- 22086397 TI - Molecularly imprinted polymers for selective extraction of synephrine from Aurantii Fructus Immaturus. AB - In this work, molecularly imprinted solid-phase extraction (MISPE) has been used to selectively enrich, purify, or remove synephrine from Aurantii Fructus Immaturus. To this end, a molecularly imprinted polymer (MIP) was prepared by self-assembly from the template synephrine, the functional monomer methacrylic acid, and the crosslinker ethylene glycol dimethacrylate in 1:4:20 molar ratio. Subsequent molecular interrogation of the MIP binding sites revealed preferential structural selectivity for synephrine relative to other structurally related naturally occurring compounds (i.e. octopamine and tyramine ). This selectivity was subsequently exploited to achieve substantial sample clean-up of extracts of crude Aurantii Fructus Immaturus and Aurantii Fructus Immaturus stir-baked with bran. The purity of synephrine in the extracts after MISPE represented approximately 24.21-fold enrichment of the synephrine in the untreated extracts of Aurantii Fructus Immaturus stir-baked with bran. High recoveries (85-90%) from the samples proved that the method was valid for selective enrichment, purification, or removal of synephrine from Aurantii Fructus Immaturus. PMID- 22086398 TI - Nanoscale analysis of surface oxides on ZnMgAl hot-dip-coated steel sheets. AB - In this work, the first few nanometres of the surface of ZnMgAl hot-dip galvanised steel sheets were analysed by scanning Auger electron spectroscopy, angle-resolved X-ray photoelectron spectroscopy and atomic force microscopy. Although the ZnMgAl coating itself is exhibiting a complex micro-structure composed of several different phases, it is shown that the topmost surface is covered by a smooth, homogeneous oxide layer consisting of a mixture of magnesium oxide and aluminium oxide, exhibiting a higher amount of magnesium than aluminium and a total film thickness of 4.5 to 5 nm. Especially by the combined analytical approach of surface-sensitive methods, it is directly demonstrated for the first time that within surface imprints--created by industrial skin rolling of the steel sheet which ensures a smooth surface appearance as well as reduced yield point phenomenon--the original, smooth oxide layer is partly removed and that a layer of native oxides, exactly corresponding to the chemical structure of the underlying metal phases, is formed. PMID- 22086399 TI - Toward the quantification of the 13CO2/12CO2 ratio in exhaled mouse breath with mid-infrared hollow waveguide gas sensors. AB - Mouse sepsis models are used to gain insight into the complex processes involved with patients suffering from glucose metabolism disorders. Measuring the expiratory release of (13)CO(2) after administering stable labeled (13)C(6) glucose enables assessment of the in vivo integrity and functionality of key metabolic processes. In the present study, we demonstrate that Fourier transform infrared spectroscopy operating in the mid-infrared spectral regime (2-20 MUm) combined with hollow waveguide gas sensing modules simultaneously serving as a miniaturized gas cell and as a waveguide are capable of quantitatively monitoring (13)CO(2) enrichment levels in low volume mouse breath samples. PMID- 22086400 TI - Fluorescent hybridization probes for nucleic acid detection. AB - Due to their high sensitivity and selectivity, minimum interference with living biological systems, and ease of design and synthesis, fluorescent hybridization probes have been widely used to detect nucleic acids both in vivo and in vitro. Molecular beacons (MBs) and binary probes (BPs) are two very important hybridization probes that are designed based on well-established photophysical principles. These probes have shown particular applicability in a variety of studies, such as mRNA tracking, single nucleotide polymorphism (SNP) detection, polymerase chain reaction (PCR) monitoring, and microorganism identification. Molecular beacons are hairpin oligonucleotide probes that present distinctive fluorescent signatures in the presence and absence of their target. Binary probes consist of two fluorescently labeled oligonucleotide strands that can hybridize to adjacent regions of their target and generate distinctive fluorescence signals. These probes have been extensively studied and modified for different applications by modulating their structures or using various combinations of fluorophores, excimer-forming molecules, and metal complexes. This review describes the applicability and advantages of various hybridization probes that utilize novel and creative design to enhance their target detection sensitivity and specificity. PMID- 22086402 TI - A triterpenoid from Thalictrum fortunei induces apoptosis in BEL-7402 cells through the P53-induced apoptosis pathway. AB - Thalictrum fortunei S. Moore, a perennial plant distributed in the southeastern part of China, has been used in Traditional Chinese Medicine for thousands of years for its antitumor, antibacterial and immunoregulatory effects. In order to investigate the active components and the mechanism of the anti-tumor effects of Thalictrum fortunei, the growth inhibitory effects of eight triterpenoids isolated from the aerial parts of the plant on tumor cell lines were examined by 3-(4,5)-dimethylthiazoy1-3,5-diphenyltetrazolium bromide (MTT) assay. The MTT assay results showed that the inhibitory activity of 3-O-beta-D-glucopyranosyl-(1 >4)-beta-D-fucopyranosyl(22S,24Z)-cycloart-24-en-3beta,22,26-triol 26-O-beta-D glucopyranoside (1) was stronger than that of the other seven tested triterpenoids on human hepatoma Bel-7402 cell line (Bel-7402), human colon lovo cells (LoVo), human non-small cells lung cancer NCIH-460 cells (NCIH-460) and human gastric carcinoma SGC-7901 cells (SGC-7901) after 48 h treatment in vitro, with the IC(50) values of 66.4, 84.8, 73.5, 89.6 MUM, respectively. Moreover, the antitumor mechanism of compound 1 on Bel-7402 cell was explored through nucleus dyeing, fluorescence assay, flow cytometry and western blot. The flow cytometric analysis results revealed that compound 1 caused apoptosis and mitochondrial membrane potential (MMP) loss in Bel-7402 cells. A fluorescence assay indicated that intracellular reactive oxygen species (ROS) were markedly provoked by compound 1 treatment compared to control cells. Immunoblot results showed that compound 1 significantly increased the expression levels of cleaved caspase-3, P53 and Bax protein, and decreased the expression level of Bcl-2 protein. These findings indicate that compound 1 inhibits the growth activity of tumor cells, probably through the P53 protein-induced apoptosis pathway. PMID- 22086401 TI - Trapping cells on a stretchable microwell array for single-cell analysis. AB - There is a need for a technology that can be incorporated into routine laboratory procedures to obtain a continuous, quantitative, fluorescence-based measurement of the dynamic behaviors of numerous individual living cells in parallel, while allowing other manipulations, such as staining, rinsing, and even retrieval of targeted cells. Here, we report a simple, low-cost microarray platform that can trap cells for dynamic single-cell analysis of mammalian cells. The elasticity of polydimethylsiloxane (PDMS) was utilized to trap tens of thousands of cells on an array. The PDMS microwell array was stretched by a tube through which cells were loaded on the array. Cells were trapped on the array by removal of the tube and relaxation of the PDMS. Once that was accomplished, the cells remained trapped on the array without continuous application of an external force and permitted subsequent manipulations, such as staining, rinsing, imaging, and even isolation of targeted cells. We demonstrate the utility of this platform by multicolor analysis of trapped cells and monitoring in individual cells real-time calcium flux after exposure to the calcium ionophore ionomycin. Additionally, a proof of concept for target cell isolation was demonstrated by using a microneedle to locally deform the PDMS membrane in order to retrieve a particular cell from the array. PMID- 22086403 TI - Acetylcholinesterase-inhibiting alkaloids from Zephyranthes concolor. AB - The bulbs and aerial parts of Zephyranthes concolor (Lindl.) Benth. & Hook. f. (Amaryllidaceae), an endemic species to Mexico, were found to contain the alkaloids chlidanthine, galanthamine, galanthamine N-oxide, lycorine, galwesine, and epinorgalanthamine. Since currently only partial and low resolution (1)H-NMR data for chlidanthine acetate are available, and none for chlidanthine, its 1D and 2D high resolution (1)H- and (13)C-NMR spectra were recorded. Unambiguous assignations were achieved with HMBC, and HSQC experiments, and its structure was corroborated by X-ray diffraction. Minimum energy conformation for structures of chlidanthine, and its positional isomer galanthamine, were calculated by molecular modelling. Galanthamine is a well known acetylcholinesterase inhibitor; therefore, the isolated alkaloids were tested for this activity. Chlidanthine and galanthamine N-oxide inhibited electric eel acetylcholinesterase (2.4 and 2.6 * 10(-5) M, respectively), indicating they are about five times less potent than galanthamine, while galwesine was inactive at 10(-3) M. Inhibitory activity of HIV-1 replication, and cytotoxicity of the isolated alkaloids were evaluated in human MT-4 cells; however, the alkaloids showed poor activity as compared with standard anti-HIV drugs, but most of them were not cytotoxic. PMID- 22086404 TI - A phase 2 study of pegylated interferon alpha-2b (PEG-Intron((r))) in children with diffuse intrinsic pontine glioma. AB - BACKGROUND: Interferon-alpha is a cytokine that has demonstrated activity in patients with supratentorial gliomas, but its ideal dose and schedule of administration is unknown. Studies suggest that low-dose, continuous exposure is more efficacious than intermittent, high doses. The authors performed a phase 2 study of recombinant interferon alpha-2b with monomethoxy polyethylene glycol (PEG-Intron((r))) in children with diffuse intrinsic pontine glioma (DIPG), a population with dismal survival despite decades of clinical investigation. The primary objective was to compare 2-year survival with a historic cohort that received radiation therapy alone. METHODS: Patients received weekly subcutaneous PEG-Intron((r)) at a dose of 0.3 MUg/kg beginning 2 to 10 weeks after the completion of radiation therapy until they developed disease progression. Patients were evaluated clinically and radiographically at regular intervals. Serum and urine were assayed for biomarkers before each cycle. Quality-of-life (QOL) evaluations were administered at baseline and before every other cycle of therapy to the parents of patients ages 6 to 18 years. RESULTS: Thirty-two patients (median age, 5.3 years; range, 1.8-14.8 years) were enrolled and received a median of 7 cycles of therapy (range, from 1 cycle to >=70 cycles). PEG-Intron((r)) was well tolerated, and no decrease in QOL scores was noted in the subset of patients tested. The 2-year survival rate was 14%, which was not significantly improved compared with the historic cohort. However, the median time to progression was 7.8 months, which compared favorably with recent trials reporting a time to progression of 5 months in a similar population. CONCLUSIONS: Although low-dose PEG-Intron((r)) therapy did not significantly improve 2-year survival in children with DIPG compared with an historic control population, it did delay the time to progression. PMID- 22086405 TI - Degree of freezing does not affect efficacy of frozen gloves for prevention of docetaxel-induced nail toxicity in breast cancer patients. AB - PURPOSE: Frozen gloves (FG) are effective in preventing docetaxel-induced nail toxicity (DNT), but uncomfortable. The preventive effect of FG for DNT was compared using a standard (-25 to -30 degrees C) or more comfortable (-10 to -20 degrees C) preparation. METHODS: Breast cancer patients receiving docetaxel were eligible. Each patient wore an FG (prepared at -10 to -20 degrees C for 90 min) for 60 min without replacement on the right hand. The left hand was protected by standard methods (FG prepared at -25 to -30 degrees C overnight and worn for 90 min with replacement at 45 min). The primary endpoint was DNT occurrence at 5 months. Secondary endpoints included docetaxel exposure [cumulative dose and area under the blood concentration time curve (AUC)] until DNT occurrence and discomfort from FG. The pharmacokinetics of docetaxel was assessed. RESULTS: From 23 patients enrolled between December 2006 and June 2010, seven who received docetaxel for less than 5 months were excluded from evaluation. The median accumulated docetaxel dose was 700 mg/m(2) (340-1430 mg/m(2)). Within 5 months of FG use, none developed protocol-defined DNT in either hand. Two patients (13%) developed DNT at 7.2 and 7.3 months, respectively, both at -10 to -20 degrees C. In the control hand (-25 to -30 degrees C), discomfort occurred in 92% of the cycles, compared to 15% in the experimental hand (-10 to -20 degrees C). Five patients (22%) experienced pain at -25 to -30 degrees C, but none did at -10 to 20 degrees C. The degree of docetaxel exposure was not related to DNT occurrence in our study. CONCLUSION: A convenient preparation of FG at -10 to -20 degrees C is almost as effective as a standard preparation at -25 to -30 degrees C, with significantly less discomfort. PMID- 22086406 TI - A dietitian-led clinic for patients receiving (chemo)radiotherapy for head and neck cancer. AB - PURPOSE: Malnutrition is prevalent in head and neck cancer patients and is associated with poorer outcomes and increased health care costs. This study aimed to evaluate the acceptability, organisational efficiency and clinical outcomes of a dietitian-led head and neck cancer clinic. METHODS: Two consecutive, independent, patient cohorts were studied with a pre-post-test design of 98 patients prior to the introduction of a dietitian-led clinic (DLC) and the subsequent 100 patients who attended the newly formulated DLC. The two groups were compared for frequency of dietitian intervention, weight loss, enteral feeding, hospital admissions and post-treatment medical follow-up requirements. RESULTS: Nutritional management in a DLC was associated with reduced nutrition related admissions from 12% to 4.5% (p = 0.0029), unplanned nasogastric tube insertions from 75% to 39% (p = 0.02), improved transition to oral diet post radiotherapy from 68.3% to 76.7% (p = 0.10) and reduced radiation oncologist review at 2 weeks post-radiotherapy from 32% to 15% patients (p = 0.009) compared to the cohort prior to the DLC. CONCLUSIONS: A dietitian-led head and neck cancer clinic is associated with improved efficiency and nutritional management of head and neck cancer patients and offers a feasible model of care. PMID- 22086407 TI - Worksite adjustments and work ability among employed cancer survivors. AB - OBJECTIVES: This study was conducted to determine how many cancer survivors (CSs) make worksite adjustments and what kinds of adjustments they make. Changes in work ability among employed CSs were explored, and clinical, sociodemographic, and work-related factors associated with the current total work ability were studied. METHODS: CSs of the ten most common invasive types of cancer for men and women in Norway completed a mailed questionnaire 15-39 months after being diagnosed with cancer. Included in the analyses were all participants who worked both at the time of diagnosis and at the time of the survey and who had not changed their labor force status since diagnosis (n = 563). The current total work ability was compared to the lifetime best (0-10 score). RESULTS: Twenty-six percent of the employed CSs had made adjustments at work, and the most common adjustment was changing the number of work hours per week. Despite the fact that 31% and 23% reported reduced physical and mental work abilities, respectively, more than 90% of the CSs reported that they coped well with their work demands. The mean total work ability score was high (8.6) among both men and women. Being self-employed and working part-time at the time of diagnosis showed significant negative correlations with total work ability, while a favorable psychosocial work environment showed a significant positive correlation. CSs with low work ability were more often in contact with the occupational health service and also made more worksite adjustments than others. CONCLUSION: The prospects of future work life seem optimistic for Norwegian employed CSs who return to work relatively soon after primary treatment. PMID- 22086408 TI - Acute-on-chronic liver failure: what are the implications? AB - Acute-on-chronic liver failure (ACLF) is a clinical entity that is well recognized by those who care for patients with cirrhosis, however in spite of this widespread recognition, there remains little consensus with regard to definition and clinical features. While many similarities exist between ACLF and decompensated cirrhosis, there are also key differences, the implications of which are far reaching for both clinicians and patients alike. Among these differences are the possibility of a reversible component, the presence of a defined insult, prognosis, and outcomes associated with ACLF (see Fig. 1). However, for ACLF to have meaningful clinical implications, it first must be defined. If ACLF can be clearly defined and more easily recognized, then clinicians may be better able to prevent, treat, prognosticate, and counsel such patients. PMID- 22086409 TI - Serological evidence for brucellosis in Bos indicus in Nigeria. AB - PURPOSE: Nigeria is the largest cattle-rearing nation in Africa with most animals kept under traditional husbandry practices. While bovine brucellosis does not receive much attention, a relatively high seroprevalence is found in samples submitted for laboratory testing. The aim of the study was to provide serological evidence of brucellosis in cattle from some of the main cattle-rearing states of the country and to validate a simple and rapid field test for the serodiagnosis of bovine brucellosis. METHOD: Serum samples collected in various states of Nigeria from cattle because of suspicion of brucellosis were investigated in the Rose Bengal plate test, and results were compared with a newly developed rapid field test for the detection of Brucella-specific antibodies. RESULTS: Serological evidence for the presence of brucellosis in cattle was obtained for all states included in the study and a high herd prevalence was observed. The seroprevalence was also high among trade and slaughter animals. Results of a rapid field test for the serodiagnosis of bovine brucellosis correlated well with the Rose Bengal plate test (agreement, 95.7%; kappa value, 0.80). CONCLUSIONS: The results indicate that bovine brucellosis is an important veterinarian problem in Nigeria. The easy-to-use and robust field test is most promising for field based surveillance as it provides an immediate result allowing the prompt instigation of control measures. PMID- 22086410 TI - Polymorphism analysis of BMPR1B gene by forced RFLP and PCR-SSCP techniques and expression of the mutation in introgressed sheep. AB - The present study was conducted to screen Kashmir valley sheep with history of prolificacy for the presence of FecB mutation. Forced polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and single strand conformation polymorphism (SSCP) techniques were employed to detect any polymorphism present in bone morphogenetic protein receptor type 1B (BMPR1B) gene. Further, it was aimed at introgressing the FecB mutation into nonprolific noncarrier sheep. A 140-bp fragment of BMPR1B gene was amplified from isolated genomic DNA and subjected to forced RFLP with restriction enzyme AvaII. Three different RFLP patterns were identified. SSCP analysis showed one-to-one correspondence with RFLP patterns. Sequencing of the samples showing different patterns revealed that the wild (+) and mutant (B) alleles were different by a single nucleotide substitution in the form of A109G from wild to mutant allele. It led to change in amino acid from Glutamine (Q) to Arginine (R) from wild to mutant allele. The mutation was only detected in NARI-Suwarna and their crosses; all Kashmir valley sheep with prolific history lacked it. The + allele was abundant in the studied population. The FecB mutation was introgressed in nonprolific noncarrier sheep by crossing ewes with NARI-Suwarna rams possessing the mutation. First generation crossing produced heterozygous (B+) progeny. Some of the F(1) heterozygous ewes gave birth to twins when mated to unrelated NARI Suwarna rams. It showed that FecB mutation was successfully expressing in those crosses. PMID- 22086411 TI - Influence of processing cassava peels on the hydrogen cyanide concentration, nutritive value and performance of growing rabbits. AB - Forty-eight rabbits used to investigate the response of growing rabbits to diets containing differently processed cassava peel meals were divided into four groups balanced for sex and weight. These groups were then assigned at random to the experimental treatments. Four diets were formulated such that the diets contained 200 g/kg of the experimental feedstuffs, sun-dried cassava peel meal (S), ensiled cassava peel meal (E) and retted cassava peel meal (R), and the control did not contain any cassava peels. Hydrogen cyanide (HCN) concentration in the processed cassava peel meal was lower relative to the unprocessed meal. It was, however, lowest in R and highest in E. With the exception of S, fibre fractions were lower in the processed meal compared to the unprocessed meal. The E depressed (p < 0.05) feed and digestible nutrient intakes, weight gain, nutrient digestibility, digestible protein (DP), digestible energy (DE) and DP/DE ratio but increased protein intake to gain and feed to gain ratios compared to other diets. Intake of HCN decreased (p < 0.05) successively in this order: R, S and E. The results indicate that retting and sun-drying are more effective in cassava peel detoxification than ensiling, and dietary HCN concentration and intake of 56 and 4 mg/kg BW, respectively, were not toxic under the conditions of the experiment. PMID- 22086412 TI - Effect of varying dietary energy levels during the last trimester of pregnancy on subsequent first lactation performance in Sahiwal heifers. AB - The aim of the study was to determine optimum dietary energy level during the last trimester of pregnancy for Sahiwal heifers in subtropical Pakistan. Sixteen Sahiwal heifers, 5-6 months pregnant, were assigned to four dietary treatments with four heifers on each treatment. Isonitrogenous (CP = 14.1%) diets having varying energy, namely, ME 88%, ME 100% (Control), ME 112% and ME 124% of NRC recommended level for pregnant heifers, were fed until calving. All were fed a similar diet after calving. Precalving weight gain was highest (P < 0.05) in heifers fed ME 112 and 124% (486 +/- 13 and 497 +/- 5 g/day, respectively) followed by ME 100% (444 +/- 7 g/day), and the lowest weight gain was recorded for ME 88% (397 +/- 8 g/day). A similar trend was observed for feed efficiency. Body condition score at calving in groups ME 124% and ME 112% was higher than ME 88% and ME 100%. Nutrient digestibility, birth weight of calves and milk composition except fat content were not influenced by energy levels. The highest daily milk yield was observed in heifers fed ME 100% followed by ME 112, 124, and 88%. We conclude that the NRC recommendation is applicable to the subtropical region. PMID- 22086413 TI - Surface IgM stimulation induces MEK1/2-dependent MYC expression in chronic lymphocytic leukemia cells. AB - Although long considered as a disease of failed apoptosis, it is now clear that chronic lymphocytic leukemia (CLL) cells undergo extensive cell division in vivo, especially in progressive disease. Signaling via the B-cell receptor is thought to activate proliferation and survival pathways in CLL cells and also has been linked to poor outcome. Here, we have analyzed the expression of the proto oncoprotein MYC, an essential positive regulator of the cell cycle, after stimulation of surface IgM (sIgM). MYC expression was rapidly increased after sIgM stimulation in a subset of CLL samples. The ability of sIgM stimulation to increase MYC expression was correlated with sIgM-induced intracellular calcium fluxes. MYC induction was partially dependent on the MEK/ERK signaling pathway, and MYC and phosphorylated ERK1/2 were both expressed within proliferation centers in vivo. Although stimulation of sIgD also resulted in ERK1/2 phosphorylation, responses were relatively short lived compared with sIgM and were associated with significantly reduced MYC induction, suggesting that the kinetics of ERK1/2 activation is a critical determinant of MYC induction. Our results suggest that ERK1/2-dependent induction of MYC is likely to play an important role in antigen-induced CLL cell proliferation. PMID- 22086414 TI - Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. AB - Since 2001, the World Health Organization classification for hematopoietic and lymphoid neoplasms has provided a framework for defining acute leukemia (AL) subtypes, although few population-based studies have assessed incidence patterns and patient survival accordingly. We assessed AL incidence rates (IRs), IR ratios (IRRs), and relative survival in the United States (2001-2007) in one of the first population-based, comprehensive assessments. Most subtypes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia/lymphoma (ALL/L) predominated among males, from twice higher incidence of T-cell ALL/L among males than among females (IRR = 2.20) to nearly equal IRs of acute promyelocytic leukemia (APL; IRR = 1.08). Compared with non-Hispanic whites, Hispanics had significantly higher incidence of B-cell ALL/L (IRR = 1.64) and APL (IRR = 1.28); blacks had lower IRs of nearly all AL subtypes. All ALL/L but only some AML subtypes were associated with a bimodal age pattern. Among AML subtypes, survival was highest for APL and AML with inv(16). B-cell ALL/L had more favorable survival than T cell ALL/L among the young; the converse occurred at older ages. Limitations of cancer registry data must be acknowledged, but the distinct AL incidence and survival patterns based on the World Health Organization classification support biologic diversity that should facilitate etiologic discovery, prognostication, and treatment advances. PMID- 22086416 TI - NOTCH1 mutations in CLL associated with trisomy 12. AB - Two recent studies reported whole-genome sequencing of chronic lymphocytic leukemia (CLL) samples and found repeated mutations in the XPO1 and NOTCH1 genes. XPO1 was found mutated in 2.4% of cases, while NOTCH1 was found mutated in 12.2% or 15.1% of CLL samples. Here we report the results of sequencing of XPO1 and NOTCH1 in 186 CLL cases. Our results confirmed frequency of XPO1 mutations. However, we found only 5 NOTCH1 mutations in 127 IGVH unmutated/ZAP70(+) CLL samples (4%), and one mutation was found in IGVH mutated/ZAP70(-) CLL for a total percentage of 1.5%. Because 4 of 6 mutated samples also showed trisomy 12, we sequenced NOTCH1 in an additional 77 cases with trisomy 12 CLLs, including 47 IGVH unmutated/ZAP70(+) cases. Importantly, we found 41.9% NOTCH1 mutation frequency in aggressive trisomy 12 CLL cases. Our data suggest that activation of NOTCH1 plays a critical role in IGVH unmutated/ZAP70(+) trisomy 12 CLL. PMID- 22086415 TI - Human MAIT and CD8alphaalpha cells develop from a pool of type-17 precommitted CD8+ T cells. AB - Human mucosal associated invariant T (MAIT) CD8(+) and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 ((++)) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17 CD161(++)CD8alphabeta(+) T cells exist in cord blood, from which a prominent MAIT cell (TCR Valpha7.2(+)) population emerges post-natally. During this expansion, CD8alphaalpha T cells appear exclusively within a CD161(++)CD8(+)/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161(++)CD8alphabeta(+) counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161(++)CD8(+) T-cell pool and the distinct phenotype and function of CD8alphaalpha cells in man. PMID- 22086417 TI - A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. AB - Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 (P = 5.35 * 10(-10)), rs204999 (P = 1.44 * 10(-9)), and rs2858870 (P = 1.69 * 10(-8)). We also confirmed a previously reported association in the same region, rs6903608 (P = 3.52 * 10(-10)). rs204999 and rs2858870 were weakly correlated (r(2) = 0.257), and the remaining pairs of SNPs were not correlated (r(2) < 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542 rs6903608-rs2858870; AGGCT, OR = 1.7, P = 1.71 * 10(-6); GAATC, OR = 0.4, P = 1.16 * 10(-4)). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR = 0.5, 95% confidence interval = 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology. PMID- 22086418 TI - Contrasting dynamic responses in vivo of the Bcl-xL and Bim erythropoietic survival pathways. AB - Survival signaling by the erythropoietin (Epo) receptor (EpoR) is essential for erythropoiesis and for its acceleration in hypoxic stress. Several apparently redundant EpoR survival pathways were identified in vitro, raising the possibility of their functional specialization in vivo. Here we used mouse models of acute and chronic stress, including a hypoxic environment and beta thalassemia, to identify two markedly different response dynamics for two erythroblast survival pathways in vivo. Induction of the antiapoptotic protein Bcl-x(L) is rapid but transient, while suppression of the proapoptotic protein Bim is slower but persistent. Similar to sensory adaptation, however, the Bcl x(L) pathway "resets," allowing it to respond afresh to acute stress superimposed on a chronic stress stimulus. Using "knock-in" mouse models expressing mutant EpoRs, we found that adaptation in the Bcl-x(L) response occurs because of adaptation of its upstream regulator Stat5, both requiring the EpoR distal cytoplasmic domain. We conclude that survival pathways show previously unsuspected functional specialization for the acute and chronic phases of the stress response. Bcl-x(L) induction provides a "stop-gap" in acute stress, until slower but permanent pathways are activated. Furthermore, pathologic elevation of Bcl-x(L) may be the result of impaired adaptation, with implications for myeloproliferative disease mechanisms. PMID- 22086419 TI - Direct infusion mass spectrometry of oxylipin-containing Arabidopsis membrane lipids reveals varied patterns in different stress responses. AB - Direct infusion electrospray ionization triple quadrupole precursor scanning for three oxidized fatty acyl anions revealed 86 mass spectral peaks representing polar membrane lipids in extracts from Arabidopsis (Arabidopsis thaliana) infected with Pseudomonas syringae pv tomato DC3000 expressing AvrRpt2 (PstAvr). Quadrupole time-of-flight and Fourier transform ion cyclotron resonance mass spectrometry provided evidence for the presence of membrane lipids containing one or more oxidized acyl chains. The membrane lipids included molecular species of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, digalactosyldiacylglycerol, monogalactosyldiacylglycerol, and acylated monogalactosyldiacylglycerol. The oxidized chains were identified at the level of chemical formula and included C(18)H(27)O(3) (abbreviated 18:4-O, to indicate four double bond equivalents and one oxygen beyond the carbonyl group), C(18)H(29)O(3) (18:3-O), C(18)H(31)O(3) (18:2-O), C(18)H(29)O(4) (18:3-2O), C(18)H(31)O(4) (18:2-2O), and C(16)H(23)O(3) (16:4-O). Mass spectral signals from the polar oxidized lipid (ox-lipid) species were quantified in extracts of Arabidopsis leaves subjected to wounding, infection by PstAvr, infection by a virulent strain of P. syringae, and low temperature. Ox-lipids produced low amounts of mass spectral signal, 0.1% to 3.2% as much as obtained in typical direct infusion profiling of normal-chain membrane lipids of the same classes. Analysis of the oxidized membrane lipid species and normal-chain phosphatidic acids indicated that stress-induced ox-lipid composition differs from the basal ox-lipid composition. Additionally, different stresses result in the production of varied amounts, different timing, and different compositional patterns of stress-induced membrane lipids. These data form the basis for a working hypothesis that the stress-specific signatures of ox-lipids, like those of oxylipins, are indicative of their functions. PMID- 22086420 TI - Polycomb group complexes mediate developmental transitions in plants. PMID- 22086421 TI - The role of CAX1 and CAX3 in elemental distribution and abundance in Arabidopsis seed. AB - The ability to alter nutrient partitioning within plants cells is poorly understood. In Arabidopsis (Arabidopsis thaliana), a family of endomembrane cation exchangers (CAXs) transports Ca(2+) and other cations. However, experiments have not focused on how the distribution and partitioning of calcium (Ca) and other elements within seeds are altered by perturbed CAX activity. Here, we investigate Ca distribution and abundance in Arabidopsis seed from cax1 and cax3 loss-of-function lines and lines expressing deregulated CAX1 using synchrotron x-ray fluorescence microscopy. We conducted 7- to 10-MUm resolution in vivo x-ray microtomography on dry mature seed and 0.2-MUm resolution x-ray microscopy on embryos from lines overexpressing deregulated CAX1 (35S-sCAX1) and cax1cax3 double mutants only. Tomograms showed an increased concentration of Ca in both the seed coat and the embryo in cax1, cax3, and cax1cax3 lines compared with the wild type. High-resolution elemental images of the mutants showed that perturbed CAX activity altered Ca partitioning within cells, reducing Ca partitioning into organelles and/or increasing Ca in the cytosol and abolishing tissue-level Ca gradients. In comparison with traditional volume-averaged metal analysis, which confirmed subtle changes in seed elemental composition, the collection of spatially resolved data at varying resolutions provides insight into the impact of altered CAX activity on seed metal distribution and indicates a cell type-specific function of CAX1 and CAX3 in partitioning Ca into organelles. This work highlights a powerful technology for inferring transport function and quantifying nutrient changes. PMID- 22086423 TI - The Psb27 assembly factor binds to the CP43 complex of photosystem II in the cyanobacterium Synechocystis sp. PCC 6803. AB - We have investigated the location of the Psb27 protein and its role in photosystem (PS) II biogenesis in the cyanobacterium Synechocystis sp. PCC 6803. Native gel electrophoresis revealed that Psb27 was present mainly in monomeric PSII core complexes but also in smaller amounts in dimeric PSII core complexes, in large PSII supercomplexes, and in the unassembled protein fraction. We conclude from analysis of assembly mutants and isolated histidine-tagged PSII subcomplexes that Psb27 associates with the "unassembled" CP43 complex, as well as with larger complexes containing CP43, possibly in the vicinity of the large lumenal loop connecting transmembrane helices 5 and 6 of CP43. A functional role for Psb27 in the biogenesis of CP43 is supported by the decreased accumulation and enhanced fragmentation of unassembled CP43 after inactivation of the psb27 gene in a mutant lacking CP47. Unexpectedly, in strains unable to assemble PSII, a small amount of Psb27 comigrated with monomeric and trimeric PSI complexes upon native gel electrophoresis, and Psb27 could be copurified with histidine-tagged PSI isolated from the wild type. Yeast two-hybrid assays suggested an interaction of Psb27 with the PsaB protein of PSI. Pull-down experiments also supported an interaction between CP43 and PSI. Deletion of psb27 did not have drastic effects on PSII assembly and repair but did compromise short-term acclimation to high light. The tentative interaction of Psb27 and CP43 with PSI raises the possibility that PSI might play a previously unrecognized role in the biogenesis/repair of PSII. PMID- 22086424 TI - Echocardiographic findings in adolescents with anorexia nervosa at beginning of treatment and after weight recovery. AB - Anorexia nervosa (AN) is an eating disorder with somatic complications. The aim of the study was to analyse echocardiographic abnormalities in patients with AN at initial examination and after weight restoration. A total of 173 consecutively admitted adolescents (aged 12-17 years), diagnosed with DSM-IV AN (307.1) were evaluated in a child and adolescent psychiatric department of a major university hospital from December 1997 to August 2008. In addition, 40 healthy adolescents of the same age with normal weight were examined. In patients with AN, 34.7% had a pericardial effusion (PE) which was clinically silent. In contrast, none of the controls presented with PE (p < 0.001). No differences across AN subtypes were observed. Patients with PE showed significantly lower body mass index (BMI) (p = 0.016) than patients without PE. They had more prominent low-T3 syndrome (p = 0.003) and longer duration of hospitalisation (p = 0.008) after controlling for BMI at admission. Remission of PE was observed in 88% of the patients after weight restoration. Left ventricular end-diastolic and end-systolic dimensions in AN were significantly lower than in controls (p < 0.001). There were no differences in interventricular septum thickness, posterior wall thickness and fractional shortening. This report indicates that adolescents with AN show cardiac abnormalities in comparison to healthy young women. Furthermore, PE is a frequent cardiac complication in patients with AN and it is associated with BMI, low T3 serum levels and duration of hospitalisation. PMID- 22086425 TI - [Characteristics and evolution of patients with Alice in Wonderland syndrome]. AB - INTRODUCTION: Alice in Wonderland syndrome is a process characterized for complex disorders of the visual perception with multiple etiologies. AIM: To evaluate the clinical, electrophysiological, etiological characteristics and natural evolution in children with Alice in Wonderland syndrome. PATIENTS AND METHODS: We have realized a retrospective study by what means of a review of 20 clinical histories of 18 year old minor patients diagnosed of Alice in Wonderland syndrome from January 1995 until February 2010. RESULTS: The average of age to the diagnosis was 9.5 +/- 3.8 years (range: 4-16 years). It appeared in an acute way in 85% and progressive in 15%. 90% had micropsias and/or macropsias, 85% distortion of the form of the objects, 80% displacement of objects, 45% disturbances of body image, 45% acceleration of the time and 30% sensation of unreality. 95% of the children had many episodes a day; these episodes lasted less than 3 minutes in 90%. Electroencephalogram was realized in all the patients, it was abnormal in 11 cases, in one case was found and epileptic foci (left temporal) and in 10 cases was found posterior slow waves. The tests of neuroimagen were normal in all the patients. The visual evoked potentials were realized in 7 children; five of these children showed higher amplitude in evoked potentials and two of these children had normal. The infectious etiology was found in nine cases (five partners to Epstein-Barr virus), migraine in eight, toxins in two and epilepsy in one case. 80% did not have recurrence. CONCLUSIONS: Alice in Wonderland syndrome is a benign process with trend to spontaneous resolution and without recurrence in the majority of the occasions. The principal etiologies are migraine and Epstein-Barr virus infection. PMID- 22086426 TI - [Psychogenic pathology in the neurology unit. A review of the hospital admissions over the last 10 years in a third-level service]. AB - INTRODUCTION: Psychogenic disorders are frequently seen in neurological practice and sometimes make it necessary to hospitalise the patient in order to rule out a potentially severe organic pathology. AIM: To determine the profile of patients with a discharge diagnosis of psychogenic disorder that are admitted to the neurology unit of a Spanish hospital. PATIENTS AND METHODS: The neurology unit discharge abstracts from the last 10 years were reviewed and the patients who were diagnosed with 'non-organicity' were selected; a total of 28 demographic, epidemiological and clinical variables were also collected. RESULTS: A total of 64 patients (1% of those admitted to hospital), with a mean age of 40 years, had a diagnosis of psychogenicity. The proportion between sexes was one to one and the mean length of stay in hospital was 10 days. Mixed symptoms were the most usual (50%), followed by isolated motor symptoms (22%). Most cases consisted of possible neurological diagnoses of ischaemic stroke and demyelinating disease. Only 25% of cases consulted psychiatry during hospitalisation. In 11% of cases there was a later history of suicide attempts and in eight cases (12.5%) an ambulatory diagnosis of organicity was reached thanks to the developmental follow up ('error' in the provisional diagnosis on discharge). CONCLUSIONS: This study traces, for the first time in our setting, the profile of the psychogenic patient who is admitted to the neurology unit and examines their hospital management and their outpatient follow-up. We highlight the need not to underestimate this pathological condition and to generate an ordered way of managing it, which should always be multidisciplinary with the leading roles played by the neurologist and the psychiatrist. PMID- 22086427 TI - [Hammersmith functional rating scale for children with spinal muscular atrophy. Validation of the Spanish version]. AB - AIMS: This study was conducted with the aim of developing the Spanish version of the Hammersmith functional rating scale for children with spinal muscular atrophy (SMA), to establish the interobserver reliability and to adapt it to Spanish children with SMA types II and III. PATIENTS AND METHODS: We assessed 31 children with a mean age of 4.7 years (range: 2.5-9 years) and they were re-assessed at 3, 6 and 12 months. The children with SMA type II could not walk and the children with SMA type III were able to walk. RESULTS: Interobserver reliability was 95%. The median of the score in the group with SMA type II was 17 (range: 0-34) and in the SMA type III group it was 39 (range: 37-40). The results of the group with SMA type II at 12 months were poorer, although not to a statistically significant extent, which suggested that the disease was getting worse. CONCLUSIONS: The Spanish version presents a high degree of interobserver reliability, is easy to administer in clinical practice and is a good tool for assessing the severity of the disease in patients with SMA, above all in those who are unable to walk. PMID- 22086428 TI - [Awareness of dysphagia in Parkinson's disease]. AB - INTRODUCTION AND AIM: In order to be able to assess the level of awareness of swallowing disorders in Parkinson's disease (PD), a specific questionnaire was designed and validated: the Dysphapark questionnaire. PATIENTS AND METHODS: A total of 470 persons with PD were asked whether they believe they have problems swallowing or not, and then they filled in a self-administered questionnaire that evaluates the effectiveness and safety of swallowing. The Dysphapark questionnaire was validated by means of Rasch analysis and classical psychometric methods. RESULTS: The safety and effectiveness dimensions of the Dysphapark fit the Rasch model well. The efficacy dimension showed significant differences for gender, length of the illness, awareness of dysphagia and length of meals. Significant differences were also found in the safety dimension for length and severity of illness, awareness of dysphagia, speech therapy and knowledge of thickening agents. Despite the fact that 90% of patients had problems concerning effectiveness and safety in swallowing, 79.45% were not aware that they suffered from dysphagia. CONCLUSIONS: The Dysphapark questionnaire is a suitable measure of dysphagia in PD, according to the Rasch analysis. A high proportion of patients with PD have dysphagia, although it has been observed that they have a low level of awareness of the condition, of the consequences it may have and of the possibility of using thickening agents. Given that some of the swallowing disorders in PD are asymptomatic and that the level of awareness of the disorder is low, we recommend including specific questionnaires as well as clinical and instrumental evaluation of dysphagia in clinical practice. PMID- 22086422 TI - Gene expression and metabolite profiling of developing highbush blueberry fruit indicates transcriptional regulation of flavonoid metabolism and activation of abscisic acid metabolism. AB - Highbush blueberry (Vaccinium corymbosum) fruits contain substantial quantities of flavonoids, which are implicated in a wide range of health benefits. Although the flavonoid constituents of ripe blueberries are known, the molecular genetics underlying their biosynthesis, localization, and changes that occur during development have not been investigated. Two expressed sequence tag libraries from ripening blueberry fruit were constructed as a resource for gene identification and quantitative real-time reverse transcription-polymerase chain reaction primer design. Gene expression profiling by quantitative real-time reverse transcription polymerase chain reaction showed that flavonoid biosynthetic transcript abundance followed a tightly regulated biphasic pattern, and transcript profiles were consistent with the abundance of the three major classes of flavonoids. Proanthocyanidins (PAs) and corresponding biosynthetic transcripts encoding anthocyanidin reductase and leucoanthocyanidin reductase were most concentrated in young fruit and localized predominantly to the inner fruit tissue containing the seeds and placentae. Mean PA polymer length was seven to 8.5 subunits, linked predominantly via B-type linkages, and was relatively constant throughout development. Flavonol accumulation and localization patterns were similar to those of the PAs, and the B-ring hydroxylation pattern of both was correlated with flavonoid-3'-hydroxylase transcript abundance. By contrast, anthocyanins accumulated late in maturation, which coincided with a peak in flavonoid-3-O glycosyltransferase and flavonoid-3'5'-hydroxylase transcripts. Transcripts of VcMYBPA1, which likely encodes an R2R3-MYB transcriptional regulator of PA synthesis, were prominent in both phases of development. Furthermore, the initiation of ripening was accompanied by a substantial rise in abscisic acid, a growth regulator that may be an important component of the ripening process and contribute to the regulation of blueberry flavonoid biosynthesis. PMID- 22086429 TI - [Takotsubo cardiomyopathy as a complication of an epileptic status]. AB - INTRODUCTION: Cardiological complications are the most frequent cause of mortality in the epileptic status. Takotsubo cardio-myopathy is a recently reported condition that can appear in a number of medical emergencies, including epileptic status. CASE REPORT: We present a case of Takotsubo cardiomyopathy within the context of an epileptic status and we also review similar cases reported in the literature. Special attention is given to the semiology and aetiology of the epileptic seizures, patients' epidemiological data, the alterations noted in the electrocardiogram and the complications that occurred. The patient, a 43-year-old female, recovered completely both cardiologically and neurologically, and did not suffer any relapses during the one-year follow-up. CONCLUSION: Takotsubo cardiomyopathy is a severe, treatable complication that can occur in the epileptic status. PMID- 22086430 TI - [Neurosurgical techniques for the neuromodulation of pain]. AB - Neuromodulation for treating pain goes back to the times of the ancient Egyptians, who applied natural electric currents to modulate the painful sensation. Since then, this concept has been developed in parallel with the scientific and technological development, and various forms of neuromodulation with different indications and characteristics have originated. Chronic pain may produce significant disability, which leads to important physical, social and psychological consequences. Peripheral nerve, spinal cord, deep brain and motor cortex stimulation are safe and effective techniques that control pain and improve quality of life in selected patients. PMID- 22086431 TI - [A vertebrobasilar infarct with a possible origin in the carotid artery]. PMID- 22086433 TI - Bilateral third nerve palsy with pupil involvement as the first manifestation of multiple sclerosis. PMID- 22086434 TI - [Collaboration between different links: one of the keys to the telestroke system]. PMID- 22086435 TI - Impact of dietary fiber coatings on behavior of protein-stabilized lipid droplets under simulated gastrointestinal conditions. AB - Multilayer emulsions containing lipid droplets coated by lactoferrin (LF) - anionic polysaccharide layers have improved resistance to environmental stresses (such as pH, salt, and temperature), but their behavior within the gastrointestinal tract (GIT) is currently unknown. The objective of this research was therefore to monitor changes in the physicochemical properties and digestibility of these systems under simulated GIT conditions. Primary emulsions (5% corn oil, 0.5% LF) were prepared using a high-pressure homogenizer. Secondary emulsions (5% corn oil, 0.5% LF, 0.5% polysaccharide) were prepared by incorporating alginate, low methoxyl pectin (LMP) or high methoxyl pectin (HMP) into primary emulsions. Emulsions were then subjected to simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) conditions in sequence. LF, LF-LMP and LF-HMP emulsions were stable to droplet aggregation in the stomach but aggregated in the small intestine, whereas LF-alginate emulsions aggregated in both the stomach and small intestine. The presence of a dietary fiber coating around the initial lipid droplets had little influence on the total extent of lipid digestion in SIF, but LF-alginate emulsions had a slower initial digestion rate than the other emulsions. These results suggest that the dietary fiber coatings may become detached in the small intestine, or that they were permeable to digestive enzymes. Pepsin was found to have little influence on the physical stability or digestibility of the emulsions. The knowledge obtained from this study is important for the design of delivery systems for encapsulation and release of lipophilic bioactive ingredients. PMID- 22086436 TI - How chromatin prevents genomic rearrangements: locus colocalization induced by transcription factor binding. AB - The loosening of chromatin structures gives rise to unrestricted access to DNA and thus transcription factors (TFs) can bind to their otherwise masked target sequences. Regions bound by the same set of TFs tend to be located in close proximity and this might increase the probability of activating illegitimate genomic rearrangements. PMID- 22086437 TI - If at first you don't succeed: try, try again. PMID- 22086440 TI - Nonpharmacological therapies for behavioral and cognitive symptoms of mild cognitive impairment. AB - OBJECTIVE: Evaluate research on nonpharmacological treatments for symptoms of mild cognitive impairment (MCI). METHOD: We searched for relevant English language articles published from 2000 to 2010 using PUBMED and PsycINFO. We included nonpharmacological interventions for treating cognitive and behavioral symptoms in persons with MCI other than cognitive/memory training, which has been reviewed elsewhere. Effect sizes and hazard ratios were calculated when possible. RESULTS: Current research points to the potential influence of behavioral interventions on behavioral symptoms. Exercise/diet interventions may alleviate cognitive deficits, especially cognitive speed and executive functioning, but possibly not memory--a domain central to MCI. Results were limited by small sample sizes, lack of rigorous methodology, short follow-ups, and the limited number of published studies. DISCUSSION: Behavioral, diet, and exercise regimens show some promise with respect to reducing behavioral and cognitive symptomology. Rigorous research studies are needed to create more certainty about their potential to complement drug and/or cognitive therapies. PMID- 22086441 TI - Activation of C-Cl by ground-state aluminum atoms: an EPR and DFT investigation. AB - The reaction of ground-state Al atoms with dichloromethane (CH(2)Cl(2)) in an adamantane matrix at 77 K yielded two mononuclear Al species. The magnetic parameters, extracted from the axial EPR spectrum of Species A/A' (g(1) = 2.0037, g(2) = g(3) = 2.0030, a(Al,1) = 1307 MHz, a(Al,2) = a(Al,3) = 1273 MHz, a(35Cl) = 34 MHz and a(37Cl) = 28 MHz) were assigned to the Al-atom insertion product, ClCH(2)AlCl. Density functional theory (DFT) calculations of the values of the Al and Cl hyperfine interaction (hfi) of the Cl(1)-Cl(2)gauche conformer were in close agreement with the experimental values of ClCH(2)AlCl. The second species, B/B', had identical magnetic parameters to those of ClCH(2)AlCl with the exception that the Al hfi was 15% smaller. Coordination of a ligand, possessing a lone pair of electrons, to the Al atom of the insertion product, [ClCH(2)AlCl]:X, could cause the a(Al) to decrease by 15%. Alternatively, it is possible that the Cl(1)-Cl(2) anti conformer of ClCH(2)AlCl is also isolated in the matrix. Support for the spectral assignments is given by calculation of the nuclear hfi of [ClCH(2)AlCl]:H(2)O and the Cl(1)-Cl(2) anti conformer of ClCH(2)AlCl using a DFT method. The potential energy hypersurface for an Al atom approaching CH(2)Cl(2), calculated at the B3LYP level, suggests that Al atom abstraction of Cl forming AlCl and CH(2)Cl is favoured in the gas phase. When produced in a matrix, the close proximity of AlCl and CH(2)Cl could account for the formation of ClCH(2)AlCl. EPR evidence was also found for the formation of the CHCl(2) radical. PMID- 22086438 TI - The cardiorenal syndrome in heart failure: cardiac? renal? syndrome? AB - There has been increasing interest on the so-called cardiorenal syndrome (CRS), defined as a complex pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other. In this review, we contend that there is lack of evidence warranting the adoption of a specific clinical construct such as the CRS within the heart failure (HF) syndrome by demonstrating that: (a) the approaches and tools regarding the definition of kidney involvement in HF are suboptimal; (b) development of renal failure in HF is often confounded by age, hypertension, and diabetes; (c) worsening of renal function (WRF) in HF may be largely independent of alterations in cardiac function; (d) the bidirectional association between HF and renal failure is not unique and represents one of the several such associations encountered in HF; and (e) inflammation is a common denominator for HF and associated noncardiac morbidities. Based on these arguments, we believe that dissecting one of the multiple bidirectional associations in HF and constructing the so-called cardiorenal syndrome is not justified pathophysiologically. Fully understanding of all morbid associations and not only the cardiorenal is of great significance for the clinician who is caring for the patient with HF. PMID- 22086442 TI - Data from extension trials: denosumab and zoledronic acid. AB - Osteoporosis and fractures that occur as a result of this condition pose a huge public health problem to society and result in morbidity and mortality to individuals. Because osteoporosis is often a result of aging, many people are not aware that therapies exist to reduce the risk of fracture. Until recently, the most common therapies used to treat osteoporosis, the oral bisphosphonates, had an inconvenient and cumbersome mode of administration. Within the last 4 years, two new parenteral antiresorptive drugs to treat osteoporosis were approved by the US Food and Drug Administration. As treatment of osteoporosis may extend for many years, the collection of long-term efficacy and safety data is warranted. This paper discusses data from the extension trials of denosumab and zoledronic acid. PMID- 22086443 TI - Laparoscopic staging of early ovarian cancer: results of a multi-institutional cohort study. AB - BACKGROUND: Minimal access surgery to stage early ovarian cancer (EOC) is still regarded as investigational among many gynecologic oncologists. Reporting outcome data from large cohorts is currently the only practical way to further define the appropriateness of minimally invasive surgery for EOC patients. We sought to investigate the safety, adequacy, and outcome of laparoscopic staging of EOC by using a multi-institutional sample. METHODS: Prospectively collected data in three gynecologic oncology service databases were searched for EOC patients undergoing laparoscopic staging. Surgical, pathologic, and oncologic outcome data were analyzed. RESULTS: The study cohort consisted of 82 women. The mean operative time was 263 +/- 81 minutes. The median estimated blood loss was 100 (range 20-3000) ml. The median number of pelvic and para-aortic lymph nodes collected was 23 (3-39) and 13 (3-43), respectively. The disease was reclassified to a higher stage in 21 women (25.6%). No conversion to laparotomy occurred, and one patient had intraoperative hemorrhage requiring blood transfusion. Thirteen patients (15.8%) experienced postoperative complications. The median follow-up period was 28.5 (range 3-86) months. Overall survival and disease-free survival for the entire cohort were 98.8% and 95.1%, respectively. In the subgroup of patients who had reached or exceeded 3 years' follow-up (n = 34), 3-year overall survival and 3-year disease-free survival were 97% and 91.2%, respectively. CONCLUSIONS: When performed by appropriately skilled surgeons, laparoscopic comprehensive staging of EOC seems feasible and adequate, with surgicopathologic results that are reproducible in different practice settings. PMID- 22086444 TI - Combined analysis of dihydropyrimidine dehydrogenase and human equilibrative nucleoside transporter 1 expression predicts survival of pancreatic carcinoma patients treated with adjuvant gemcitabine plus S-1 chemotherapy after surgical resection. AB - BACKGROUND: Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival in some patients, the effectiveness varies by individual, and the results remain unsatisfying. The aim of this study was to investigate whether intratumoral dihydropyrimidine dehydrogenase (DPD) and human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of PDAC patients treated with adjuvant gemcitabine plus S-1 (GEM+S-1) chemotherapy. METHODS: Intratumoral DPD and hENT1 expression were examined by immunohistochemistry in 86 PDAC patients who received adjuvant GEM+S-1 chemotherapy after surgical resection (all R0 or R1). Relationships between clinicopathologic factors, including DPD and hENT1 expression, and disease-free or overall survival were evaluated by univariate and multivariate analyses. RESULTS: DPD and hENT1 expression had no significant relationship with any other clinicopathologic factors. A multivariate disease-free survival analysis revealed that lymph node metastasis (hazard ratio [HR], 2.90: 95% confidence interval [CI], 1.51-5.90; P = 0.001), DPD expression (HR 2.47; 95% CI 1.37-4.44; P = 0.003), and hENT1 expression (HR 2.55; 95% CI 1.37-4.64; P = 0.004) as independent factors. Multivariate overall survival analysis also identified pT factor (HR 3.47; 95% CI 1.08-15.8; P = 0.03), lymph node metastasis (HR 2.08; 95% CI 1.01-4.57; P = 0.04), DPD expression (HR 1.98; 95% CI 1.06-3.71; P = 0.03), and hENT1 expression (HR 2.18; 95% CI 1.10-4.19; P = 0.02) as independent factors. CONCLUSIONS: Combined analysis of DPD and hENT1 expression predicts the survival of PDAC patients treated with adjuvant GEM+S-1 chemotherapy. PMID- 22086445 TI - Transient but not stable ZEB1 knockdown dramatically inhibits growth of malignant pleural mesothelioma cells. AB - BACKGROUND: The role of ZEB1, a master epithelial-to-mesenchymal transition gene, in malignant pleural mesothelioma (MPM) is unclear. METHODS: The expression of ZEB1, E-cadherin, vimentin, and epithelial cell adhesion molecule (EpCAM) in 18 MPM cell lines and a normal pleural mesothelial cell line MeT-5A was determined by quantitative real-time polymerase chain reaction and Western blot testing. RNA interference-mediated transient and/or stable knockdown of ZEB1 and EpCAM was performed. Microarray expression analysis was performed with a TORAY-3D gene chip. Growth was evaluated by colorimetric proliferation and colony formation assays. Luciferase reporter assay was performed to access the effects of ZEB1 knockdown on EpCAM promoter activity. RESULTS: Most MPM cell lines exhibited mesenchymal phenotype and expressed ZEB1. Transient ZEB1 knockdown suppressed growth in all four cell lines studied (ACC-MESO-1, H2052, Y-MESO-8A, Y-MESO-29) while stable ZEB1 knockdown suppressed growth only in Y-MESO-29. Genome-wide gene expression analysis revealed that EpCAM was the most prominently up-regulated gene by both transient and stable ZEB1 knockdown in ACC-MESO-1, with more marked up-regulation in stable knockdown. We hypothesized that EpCAM up-regulation counteracts the stable ZEB1 knockdown-induced growth inhibition in ACC-MESO-1. Transient EpCAM knockdown suppressed growth dramatically in ACC-MESO-1 cells expressing shZEB1 but only modestly in those expressing shGFP, supporting our hypothesis. Luciferase reporter assay showed that ZEB1 knockdown resulted in increased EpCAM promoter activity. EpCAM was also up-regulated in Y-MESO-29 expressing shZEB1, but this EpCAM up-regulation did not counteract ZEB1knockdown induced growth suppression, suggesting that the counteracting effects of EpCAM may be cellular context dependent. CONCLUSIONS: RNA interference-mediated ZEB1 knockdown may be a promising therapeutic strategy for MPM, but one has to consider the possibility of diminished growth inhibitory effects of long-term ZEB1 knockdown, possibly as a result of EpCAM up-regulation and/or other gene expression changes resulting from ZEB1 knockdown. PMID- 22086446 TI - Ethical considerations in clinical research. PMID- 22086447 TI - Bortezomib-induced sensitization of malignant human glioma cells to vorinostat induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage. AB - Glioblastomas are invasive tumors with poor prognosis despite current therapies. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth, and we and others have noted some antiglioma activity from HDACIs, such as vorinostat, although insufficient to warrant use as monotherapy. We have recently demonstrated that proteasome inhibitors, such as bortezomib, dramatically sensitized highly resistant glioma cells to apoptosis induction, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with vorinostat treatment alone, the combination of vorinostat plus bortezomib significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib with vorinostat enhanced apoptosis by increasing Mcl-1 cleavage, Noxa upregulation, Bak and Bax activation, and cytochrome c release. Further downregulation of Mcl-1 using shRNA enhanced cell killing by the bortezomib/vorinostat combination. Vorinostat induced a rapid and sustained phosphorylation of histone H2AX in primary GBM and T98G cells, and this effect was significantly enhanced by co-administration of bortezomib. Vorinostat/bortezomib combination also induced Rad51 downregulation, which plays an important role in the synergistic enhancement of DNA damage and apoptosis. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients. PMID- 22086450 TI - Comparing the performance of QuantiFERON-TB Gold and Mantoux test in detecting latent tuberculosis infection among Iranian health care workers. AB - OBJECTIVES: The risk of transmission of Mycobacterium tuberculosis from patients with tuberculosis to health care workers (HCWs) has been well documented but little is known about the prevalence of latent tuberculosis infection (LTBI) in Iranian HCWs. The aim of this study was to determine the prevalence of LTBI among HCWs by using IFNgamma-release assay and compare the results with those of tuberculin skin test (TST). METHODS: Two hundred HCWs were evaluated with both TST and QuantiFERON-TB Gold In Tube test (QFT-GIT). The obtained data were analyzed by SPSS v.16 Software. RESULTS: The participants were 73 males and 127 females with the mean age of 34.36+/-8.26 years. TST was positive in 105 cases (52.5%) and the QFT results were positive in 17 cases (8.5%). There was poor agreement between the two tests (53%, kappa = 0.115). Induration diameter of TST >= 10 mm and working duration >= 10 years were independent predictors for positive QFT (p = 0.004). CONCLUSIONS: Due to the fact that BCG vaccination has been administered routinely to all HCWs in Iran, specific tests should be introduced for high risk groups. QFT thus seems to be more effective for LTBI diagnosis than TST among HCWs with BCG immunization history. PMID- 22086449 TI - Validation of the respiratory toxics exposure score (RTES) for chronic obstructive pulmonary disease screening. AB - OBJECTIVE: Our aim is to evaluate the validity of exhaled carbon monoxide (CO) and of a newly-created score as markers of Chronic Obstructive Pulmonary Disease (COPD). MATERIALS AND METHODS: The CO level was measured in a derivation subsample of a cross-sectional study and linked to COPD diagnosis; its predictors were evaluated, and a scale was constructed. It was evaluated in a validation subsample and in a clinical setting. RESULTS: Individuals with COPD had higher CO levels than healthy individuals. CO level significant predictors were cigarettes per day, waterpipes per week, lower age, male gender, living close to diesel exhaust, heating home with the use of diesel, and having indoor family smokers. A score composed of CO predictors was able to significantly predict COPD (Ora = 4 7.5). CONCLUSIONS: Coupled with the clinical judgment of physicians, this scale would be an excellent low-cost tool for screening COPD, in absence of spirometry. PMID- 22086451 TI - Effect of regular physical activity on non-lipid (novel) cardiovascular risk factors. AB - OBJECTIVES: Cardiovascular - coronary heart disease, causing heart attack and heart failure is a leading cause of disability and death worldwide. The most important risk factors for CVD are well-established and physical activity has long been considered the cornerstone of interventions and has shown extremely important in reducing the burden of this disease. The aim of this study was to examine the association between activity and inactivity and non-lipid CVD risk factors in healthy military recruits. MATERIALS AND METHODS: Selected hormones and variables such as testosterone, free testosterone, Vitamin D, homocysteine, folic acid, with the inflammatory cytokines such as hsCRP, TNF-alpha and IL-6 were assessed in two groups (active = 50, inactive = 50), randomly matched by a questionnaire. Relationships between some measured variables and CVD risk factors were determined using simple correlation procedures. RESULTS: Physically active subjects had significantly lower results of homocysteine (14.3+/-1.9 vs. 16.5+/ 3.7, p < 0.000) and interleukin-6 (2.9.+/-5.3 vs. 6+/-8.2, p< 0.025) and tended to have a nearly significantly higher free testosterone level (13.1+/-7.1 vs. 11+/-5.3, p = 0.08). Significant correlations were found between BMI, WC, tHcy, and the corresponding risk factors; and also between hsCRP and IL-6, as well as TT and FT. CONCLUSIONS: Reducing the risk factors of developing CVD events such as homocysteine and interleukin-6, together with increasing free testosterone and significantly preventing its progression, clearly serve to underscore the beneficial properties of physical activity and to promote its effectiveness as a support means for healthier lifestyles in the community and, particularly, among military personnel. PMID- 22086452 TI - Polish mother and child cohort study (REPRO_PL)--methodology of follow-up of the children. AB - BACKGROUND: A prospective cohort study design gives the opportunity for identification, update of different exposures and their verification by biomarker measurements. The aim of The Polish Mother and Child Cohort Study (REPRO_PL) is to evaluate the impact of exposure to different environmental factors during pregnancy and, after birth, on the pregnancy outcome, children's health and neurodevelopment. MATERIALS AND METHODS: REPRO_PL cohort was established in 2007. From the cohort of 1300 mother-child pairs, 300 children are followed-up until they are two years old to asses the exposure, health status and neurodevelopment. Children are examined twice: at one and two years of age by a pediatrician and a psychologist/child development specialist. During each visit, detailed questionnaire is conducted with the mothers and supplemented with the information from the medical charts to have appropriate recognition of the child's health and development. Additionally, the current health status of the child is checked and his/her biometry is performed. A urine sample is collected from each child for the verification of environmental tobacco smoke (ETS) and polycyclic aromatic hydrocarbons (PAH) exposure. Some children have a blood sample collected for the assessment of the lead and cadmium levels. Child's neurodevelopment is assessed based on Bayley Scales for Infant and Toddler Development (Bayley-III). RESULTS AND CONCLUSIONS: The results of the study will become available within the next few years and will help to determine the impact of the environmental exposures on children's health and neurodevelopment. REPRO_PL cohort is a middle-sized cohort, very much focused on specific research questions with the potential for future extension and cooperation. PMID- 22086453 TI - Asbestos abatement workers versus asbestos workers: exposure and health-effects differ. PMID- 22086455 TI - The urea renaissance. AB - Over the last decade the use of urea derivatives as useful reagents, catalysts, and structural features in organic chemistry has increased rapidly. They now find utility as hydrogen-bond donors in organocatalysts and anion transporters, as important scaffolds in supramolecular chemistry, as lithiation directors, amination substrates, and promoters of metalation, and as substrates for novel rearrangement reactions. Highlighted herein is the remarkably rapid and recent development of the chemistry of ureas, which for many years had been considered unreactive, intractable, and of little value. PMID- 22086457 TI - Living-donor liver transplantation for moderate or severe porto-pulmonary hypertension accompanied by pulmonary arterial hypertension: a single-centre experience over 2 decades in Japan. AB - BACKGROUND: Candidates for orthotopic liver transplantation (OLT) often have porto-pulmonary hypertension (PPHTN) with pulmonary arterial hypertension (PAH). Poor outcomes of PPHTN contraindicate OLT. There are no guidelines for living donor liver transplantation (LDLT) in PPHTN patients. METHODS: We present our experiences of LDLT in six patients with moderate or severe PPHTN, along with our institutional guidelines. Three had liver cirrhosis and three were non-cirrhotic. Catheterization studies were undertaken before, during and after LDLT, and the mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary vascular resistance and total peripheral resistance (TPR) were monitored. RESULTS: The results showed significant differences in CO and TPR between cirrhotic and non cirrhotic patients before, during and after LDLT. Cirrhotic patients showed systemic hyperdynamic state. Two cirrhotic patients showed poor responses to pre transplant treatment, and continued to have increased PAH and poor clinical courses after LDLT. LDLT has an advantage of flexible timing of LT. Currently in our institution, PPHTN patients with mPAP <40 mmHg are registered for LDLT after treatment and catheterization. However, LDLT is performed when mPAP is <=35 mmHg, leading to improved outcomes. CONCLUSION: PPHTN patients with well-controlled PAH, or secondary PAH resulting from porto-systemic shunts, may be appropriate candidates for LDLT after careful considerations. PMID- 22086458 TI - Application of direct thermal desorption gas chromatography time-of-flight mass spectrometry for determination of nonpolar organics in low-volume samples from ambient particulate matter and personal samplers. AB - Direct thermal desorption and in-situ derivatization thermal desorption methods in conjunction with gas chromatography time-of-flight mass spectrometry have been characterized and evaluated for analysis of trace components from filters loaded with ambient particulate matter (PM). The limits of quantification were in the range of 7-24 pg for n-alkanes, 20 pg for hopanes, and 4-22 pg for polycyclic aromatic hydrocarbons (PAH). The limit of quantification was defined as the minimum amount of substance that conforms to the minimum distinguishable signal plus 9 times the standard deviation of this background signal from PM-loaded filters. The method has been successfully applied to low-volume samples from ambient PM collected with stationary and personal samplers. Stationary samples were collected in winter 2008 and 2010 in Augsburg, Germany. Sample aliquots of 0.2-0.3 m3 from stationary sampling were analyzed. High diurnal variation in concentration and source contribution was found especially during periods with low wind speed and low mixing layer height. High contributions of solid fuel combustion (wood and coal) were found in evening and nighttime samples, leading to peak PAH concentrations at midnight more than 10 times higher than at noon. Finally, the method was applied to samples collected by means of a personal sampler, i.e. a micro aethalometer, in Xi'an, China. Quantitative data on n alkanes, hopanes, and PAH were obtained from sample volumes of 17 and 24 l. The impact of different sources such as vehicular and biogenic emissions could be distinguished. PMID- 22086459 TI - Combinable poly(dimethyl siloxane) capillary sensor array for single-step and multiple enzyme inhibitor assays. AB - We describe a new method for fabricating a capillary-type sensor, called a combinable poly(dimethyl siloxane) (PDMS) capillary (CPC) sensor. The method for preparing the CPC simplifies enzyme inhibitor assays into a simple, single step assay. The sample inhibitor solution is introduced by capillary action. This triggers the spontaneous dissolution of physically adsorbed fluorescent substrates, and the substrate mixes with the inhibitor. This is followed by competitive reaction with insoluble enzyme to give a fluorescence response. CPC is composed of a convex-shaped PDMS stick containing reagents immobilized in an insoluble coating, and a concave-shaped PDMS stick containing reagents immobilized in a soluble coating. Since the concave-shaped PDMS has a deeper channel than the convex structure, combining these PDMS sticks is like closing the zipper of a "freezer bag". This allows easy fabrication of "thin and long" capillary structures containing different reagents inside the same capillary, without the need for precise alignment. This method allows the immobilization of two reactive reagents, such as enzyme and substrate required for a single step assay, which are typically very difficult to immobilize using commercially available conventional capillaries. Furthermore, by simply arraying various CPCs, the CPC sensor allows multiple assays. Here, we carried out a single-step enzyme inhibitor assay using the CPC. In addition, two independent CPCs were arrayed to demonstrate multiple assaying of a protease inhibitor. PMID- 22086460 TI - A comparative study on the B12N12, Al12N12, B12P12 and Al12P12 fullerene-like cages. AB - The stability, geometry and electronic structure of the title nanoclusters were compared by using density functional theory (DFT) calculations. Their electrical property analysis showed that the relative magnitude of the HOMO-LUMO gaps (eV) that are average values from the calculated results with five different DFT functionals is as follows: B12N12(7:02)>>Al12N12(4.09)>B12P12(3.80)>Al12P12(3.39). Computing the standard enthalpy and the Gibbs free energy of formation, it was found that the B(12)N(12) structure is thermodynamically stable at 298 K and 1 atmosphere of pressure, while the Al(12)N(12) structure may be stable at low temperatures. Due to positive values of change of enthalpy and entropy of formation for both the B(12)P(12) and Al(12)P(12) clusters, it seems that their formation from the consisting atoms is not spontaneous at any temperature. PMID- 22086461 TI - Aminoglycoside induced nephrotoxicity: molecular modeling studies of calreticulin gentamicin complex. AB - Gentamicin is a member of aminoglycoside group of broad spectrum antibiotics. It impairs protein synthesis by binding to A site of the 30S subunit of bacterial ribosomes. One of the main side effects of this drug is nephrotoxicity. The drug is known to bind to calreticulin, a chaperone essential for the folding of glycosylated proteins. We provide a detailed structural insight of the calreticulin-gentamicin complex by molecular modeling and the binding of the drug in the presence of explicit solvent was analyzed by molecular dynamics simulation. The gentamicin molecule binds to the lectin site of the calreticulin and lies in the concave channel formed by the long beta sheets. It makes interactions with residues Tyr109, Asp125, Asp135, Asp317 and Trp319 which are crucial for the chaperone function of the calreticulin. The superimposing of the modeled complex with the only available crystal structure complex of calreticulin with a tetrasaccharide (Glc(1)Man(3)) shows interesting features. First, the rings of the gentamicin occupy the positions of glucose and the first two mannose sugars of the tetrasaccharide molecule. Second, the oxygen atoms of the glycosidic linkage of these two ligands have a positional deviation of 1.3 A. The predicted binding constant of 16.9 MUM is in accordance with the previous kinetic study experiments. The details therefore, strongly implicate gentamicin as a competitive inhibitor of sugar binding with calreticulin. PMID- 22086462 TI - Systematics-guided bioprospecting for bioactive microbial natural products. AB - Advances in the taxonomic characterization of microorganisms have accelerated the rate at which new producers of natural products can be understood in relation to known organisms. Yet for many reasons, chemical efforts to characterize new compounds from new microbes have not kept pace with taxonomic advances. That there exists an ever-widening gap between the biological versus chemical characterization of new microorganisms creates tremendous opportunity for the discovery of novel natural products through the calculated selection and study of organisms from unique, untapped, ecological niches. A systematics-guided bioprospecting, including the construction of high quality libraries of marine microbes and their crude extracts, investigation of bioactive compounds, and increasing the active compounds by precision engineering, has become an efficient approach to drive drug leads discovery. This review outlines the recent advances in these issues and shares our experiences on anti-infectious drug discovery and improvement of avermectins production as well. PMID- 22086463 TI - Gene expression modulation by heat stress in Acidithiobacillus ferrooxidans LR. AB - During bioleaching, Acidithiobacillus ferrooxidans is subjected to different types of stress, including heat stress, which affect bacterial growth. In this work, real time quantitative PCR was used to analyze the expression of heat shock genes, as well as genes that encode proteins related to several functional categories in A. ferrooxidans. Cells were submitted to long-term growth and heat shock, both at 40 degrees C. The results showed that heat shock affected the expression levels of most genes investigated, whilst long-term growth at 40 degrees C resulted in minor changes in gene expression, except for certain genes related to iron transport, which were strongly down-regulated, suggesting that the iron processing capability of A. ferrooxidans was affected by long-term growth at 40 degrees C. A bioinformatic analysis of the genes' promoter regions indicated a putative transcriptional regulation by the sigma(32) factor in 12 of the 31 genes investigated, suggesting the involvement of other regulatory mechanisms in the response of A. ferrooxidans to heat stress. PMID- 22086464 TI - Sertraline inhibits formalin-induced nociception and cardiovascular responses. AB - The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8/per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg.kg-1.day-1, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5% (50 uL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 +/- 14.7%), mean arterial pressure (+1.4 +/- 3 mmHg), heart rate (+13 +/- 6.8 bpm), respiratory frequency (+4.6 +/- 5 cpm) and serum 5-HT increased to 1162 +/- 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 +/- 6.9%, -3.3 +/- 2 mmHg, -13.1 +/- 10.8 bpm, 9.8 +/- 5.7 cpm) and serum 5-HT level dropped to 634 +/- 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism. PMID- 22086465 TI - Effects of simultaneous exposure to stress and nicotine on nicotine-induced locomotor activation in adolescent and adult rats. AB - Preclinical studies have shown that repeated stress experiences can result in an increase in the locomotor response to the subsequent administration of drugs of abuse, a phenomenon that has been termed behavioral cross-sensitization. Behavioral sensitization reflects neuroadaptive processes associated with drug addiction and drug-induced psychosis. Although cross-sensitization between stress and drug-induced locomotor activity has been clearly demonstrated in adult rats, few studies have evaluated this phenomenon in adolescent rats. In the present study, we determined if the simultaneous exposure to stress and nicotine was capable of inducing behavioral sensitization to nicotine in adolescent and adult rats. To this end, adolescent (postnatal day (P) 28-37) and adult (P60-67) rats received nicotine (0.4 mg/kg, sc) or saline (0.9% NaCl, sc) and were immediately subjected to restraint stress for 2 h once a day for 7 days. The control group for stress was undisturbed following nicotine or saline injections. Three days after the last exposure to stress and nicotine, rats were challenged with a single dose of nicotine (0.4 mg/kg, sc) or saline and nicotine-induced locomotion was then recorded for 30 min. In adolescent rats, nicotine caused behavioral sensitization only in animals that were simultaneously exposed to stress, while in adult rats nicotine promoted sensitization independently of stress exposure. These findings demonstrate that adolescent rats are more vulnerable to the effects of stress on behavioral sensitization to nicotine than adult rats. PMID- 22086466 TI - MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma. AB - The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1 positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229 6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293 3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC. PMID- 22086467 TI - Postural balance in patients with social anxiety disorder. AB - Body stability is controlled by the postural system and can be affected by fear and anxiety. Few studies have addressed freezing posture in psychiatric disorders. The purpose of the present study was to assess posturographic behavior in 30 patients with social anxiety disorder (SAD) and 35 without SAD during presentation of blocks of pictures with different valences. Neutral images consisted of objects taken from a catalog of pictures, negative images were mutilation pictures and anxiogenic images were related to situations regarding SAD fears. While participants were standing on a force platform, similar to a balance, displacement of the center of pressure in the mediolateral and anteroposterior directions was measured. We found that the SAD group exhibited a lower sway area and a lower velocity of sway throughout the experiment independent of the visual stimuli, in which the phobic pictures, a stimulus associated with a defense response, were unable to evoke a significantly more rigid posture than the others. We hypothesize that patients with SAD when entering in a situation of exposure, from the moment the pictures are presented, tend to move less than controls, remaining this way until the experiment ends. This discrete body manifestation can provide additional data to the characterization of SAD and its differentiation from other anxiety disorders, especially in situations regarding facing fear. PMID- 22086468 TI - Endovascular stent placement for the treatment of nutcracker syndrome. AB - A patient presented with recurrent macroscopic hematuria, persistent orthostatic proteinuria and intermittent flank pain for 12 months. Doppler ultrasound, computed tomography angiography and selective renal vein phlebography revealed the compression of the left renal vein by the abdominal aorta. The patient was diagnosed with nutcracker syndrome and underwent endovascular stent placement. No intraoperative or postoperative complications occurred. The clinical symptoms completely resolved 14 days after the operation. At a follow-up of 6 months, the patient continued to be asymptomatic. PMID- 22086469 TI - Is there a link between Escherichia coli septicemia and the onset of systemic lupus erythematosus? Comment on: overlapping juvenile idiopathic arthritis and systemic lupus erythematosus: a case report (Rheumatol Int. 2011 May; 31(5):695 698). PMID- 22086470 TI - Cross-cultural adaptation, validation, and responsiveness of the Korean version of the AUSCAN Osteoarthritis Index. AB - The Australian/Canadian Osteoarthritis Hand Index (AUSCAN) is a patient self reported 15-item questionnaire measuring the severity of hand osteoarthritis symptoms in the respect of pain, stiffness, and function. In this study, we developed a Korean version of the AUSCAN Index (K-AUSCAN) and confirmed its reliability, validity, and responsiveness. The AUSCAN Index was translated into Korean by 3 translators and translated back into English by 3 different translators. In a group of 53 patients with clinical hand osteoarthritis (mean age 58.3 +/- 7.6 years), validity was evaluated against other outcome measures, including the Functional Index for Hand Osteoarthritis (FIHOA) and Multidimensional Health Assessment Questionnaire (MDHAQ). Test-retest reliability was assessed at a 2-weeks interval in 51 patients. Internal consistency of K AUSCAN was evaluated by Cronbach's alpha. Responsiveness was measured by standardized response mean (SRM). The test-retest reliability of K-AUSCAN yielded intraclass correlation coefficient of 0.46 for pain, 0.58 for stiffness, and 0.67 for function. The internal consistency of K-AUSCAN was satisfactory with Cronbach's alpha of 0.89 for pain and 0.93 for function. The K-AUSCAN index showed good correlation with other measures (r (2) was 0.67 for K-AUSCAN pain and MDHAQ pain; r (2) was 0.72 for K-AUSCAN function and FIHOA). The pain and function of K-AUSCAN correlated substantially with each other and moderately with stiffness subscale. The average SRM for K-AUSCAN pain, stiffness, and function was -0.92, -0.48, and -0.84, respectively. The Korean version of the AUSCAN Index is a valid, reliable, and responsive tool for the assessment of hand osteoarthritis symptoms. PMID- 22086471 TI - Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study. AB - Ankylosing spondylitis (AS) is characterized by gradual cementation of the vertebrae, a process that is described by excessive extracellular matrix remodeling. Specific matrix metalloproteinase (MMP)-derived collagen fragments are released to the circulation, and measurement of those might act as biomarkers of ankylosis. The aim of the study was to investigate the diagnostic value of five novel assays measuring different collagen species. Five newly developed ELISAs measuring MMP-degraded collagen fragments in serum of 40 AS patients and 40 age-matched controls were measured: collagen type I (C1M), type II (C2M), type III (C3M), type IV (C4M) and type VI (C6M) as well as the bone formation marker osteocalcin. The levels of the five collagen neoepitopes were significantly higher in AS patients, except for osteocalcin. Cartilage degradation (C2M) was only significantly correlated with the basement membrane (C4M) in the AS patients. In contrast, C3M was significantly correlated with all of the other collagen markers. The highest diagnostic value was achieved when combining the C2M, C3M and C6M markers, AUC 87% (P < 0.0001). Moreover, a combination of the markers correlated with the clinical mSASS score (P = 0.004, R = 0.44). Novel and unique biomarkers of tissue remodeling may provide diagnostic value and aid in understanding of the AS pathology. Each of the biomarkers tells a unique story, and by combining them in a panel there, we found a strong correlation with mSASSS. We speculate that such panel will be a valuable tool for monitoring patients as effect of treatment, for the prediction of responders and for diagnostic purposes. PMID- 22086472 TI - Evaluation of the mean platelet volume in children with familial Mediterranean fever. AB - To evaluate the Mean Platelet Volume (MPV) levels in children diagnosed with familial Mediterranean fever (FMF), during attack and attack-free periods. The records of a total of 117 children with FMF, diagnosed using the Tel-Hashomer criteria, have been scanned. The study consisted of 53 patients during an attack (group 1), 64 patients in attack-free period (group 2), and 57 healthy controls (group 3). Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded. The MPV and platelet values in FMF patients during attack (group 1) and FMF patients during attack-free periods (group 2) have been found to be significantly higher than those of the health control group (group 3). Positive correlation has been found between the MPV and platelet values in Group 1 and the disease's severity score (r = 0.224, and r = 0.268, respectively). Positive correlation (r = 0.528, and r = 0.485, respectively) has been also identified between MPV and blood platelet count in patients in Group 1 and 2. No correlation was found between the Colchicine treatment period and MPV (r = -0.005). The MPV values in the complete group of FMF diagnosed children have been found to be much higher compared to those in healthy children. As a consequence, we consider the MPV value as a useful marker that demonstrates the risk of early stage atherosclerosis in children with FMF. PMID- 22086473 TI - Spinal cord stimulation: a review. AB - Spinal cord stimulation (SCS) is a safe and effective treatment of a variety of chronic pain conditions. As our understanding of the mechanisms of action and potential uses of SCS has evolved, clinical and technological advancements have followed. This review provides an overview of potential mechanisms of action of SCS, evidence for its effectiveness, potential complications, and highlights of developing areas of interest. PMID- 22086474 TI - Residents contributing to inpatient quality: blending learning and improvement. AB - BACKGROUND: Quality improvement (QI) initiatives reduce medical errors and are an important aspect of resident physician training. Many institutions have limited funding and few QI experts, making it essential to develop effective programs that require only modest resources. We describe a resident-led, hospitalist facilitated limited root cause analysis (RCA) QI program developed to meet training needs and institutional constraints. METHODS: We initiated a monthly quality improvement conference (QIC) at the Mount Sinai Hospital in New York City, New York. Before each conference, a third-year resident investigated a patient care issue and completed a limited RCA. At the QIC, the findings were presented to the Internal Medicine residents, followed by a chief resident and hospitalist-facilitated group discussion. All proposed interventions were recorded, and selected interventions were later implemented. The success of these interventions in achieving permanent system-wide change or resident behavior change was tracked. Residents' views on the conferences were solicited via an anonymous questionnaire. RESULTS: Twenty conferences were held over the first 22 months of the program. Twenty-five (54%) of the 46 suggested interventions were initiated. Eighteen (72%) attempted interventions resulted in system-wide change or resident behavior change. Fifty-three residents evaluated the quality of the conferences. The majority believed the conferences were high quality (98%) and led to patient care improvements (96%). CONCLUSIONS: Resident-led modified RCAs are an effective method of integrating QI efforts into resident training. As front line providers, residents are uniquely positioned to identify and implement system changes that benefit patients. Conferences were implemented without overburdening facilitators or participants. PMID- 22086475 TI - Scintigraphic imaging in Tako-Tsubo cardiomyopathy. AB - Tako-Tsubo cardiomyopathy (TTC, stress cardiomyopathy) is more common in elderly women and its symptoms can be deceptively similar to those of acute myocardial infarction. Although coronary arteries appear normal on coronary angiograms, a shape like a Tako-Tsubo (a Japanese fishing pot for trapping octopuses) can be observed on left ventriculogram. TTC is generally considered to be a trigger for sudden cardiac death. The onset mechanism of TTC is still controversial. Catecholamine cardiotoxicity and/or coronary circulation disturbance due to coronary microvascular spasm and/or neurogenic stunned myocardium as a result of autonomic imbalance are considered to be the most likely causes. In this review, we assess the usefulness of myocardial scintigraphic imaging in TTC patients on the basis of the results obtained from earlier studies and case reports in order to establish a deeper understanding of the pathophysiological mechanism of this syndrome. PMID- 22086476 TI - Coincidence of coronary artery disease and Tako-Tsubo cardiomyopathy. AB - Tako-Tsubo cardiomyopathy (TTC) predominantly affects elderly people with a high prevalence of cardiovascular risk factors. Therefore, one would expect to encounter incidental coronary artery disease in a significant number of cases. In fact, the prevalence of mild coronary artery disease (CAD), by angiography, has been reported to be in the range of 30%-60%. Similarly, more severe stenotic lesions in at least one coronary vessel were incidentally found in 10%-35% of patients with the disease. Using intravascular ultrasound in a series of 10 patients with TTC, coronary atherosclerosis was demonstrable in all patients, although five patients had normal coronary angiograms. Therefore, TTC and CAD are not mutually exclusive disease entities. The incidental finding of coronary lesions, even if significant, should not automatically lead to a dismissal of the diagnosis of TTC. Rather, a case-by-case approach using additional imaging modalities should be endorsed. PMID- 22086477 TI - [Historical and current pathophysiological concepts of stress (Tako-Tsubo) cardiomyopathy]. AB - Tako-Tsubo cardiomyopathy (TTC), also referred to as stress cardiomyopathy (SCM), was first described in the 1990s and is characterized by transient left ventricular dysfunction. Its incidence represents 1-2% of all acute coronary syndromes (ACS). In most cases extreme emotional or physical stress precedes this syndrome. The majority of patients affected are postmenopausal women. Since its first description, various hypotheses regarding the pathophysiology of TTC have been discussed. From a historical perspective, coronary vasospasm has often been proposed as a possible cause of this disorder. However, reviews from numerous registries were able to demonstrate that coronary vasospasm plays only a minor role in the pathogenesis of TTC. Several groups showed disturbances in myocardial microcirculation and energy metabolism in the acute phase of TTC. Nevertheless, with regard to the data currently available, it cannot be differentiated whether these changes are the cause or rather the result of TTC. However, recent concepts include an excessive catecholamine overload and morphological changes which are unequivocally documented in TTC. The relation between elevated catecholamine levels and myocardial dysfunction analogous to TTC could be confirmed in animal experiments.In summary, it can be assumed that TTC is caused by an excessive cardiotoxic release of catecholamines. Ventricular dysfunction can be explained by increased numbers of beta-adrenergic receptors in the apex, leading to greater vulnerability to catecholamine overload. Individual anatomical differences in the sympathoadrenergic system and distribution from beta-adrenergic receptors are presumably responsible for the interindividual occurrence of wall motion abnormalities in TTC. PMID- 22086478 TI - [Complications during exercise testing]. AB - Exercise electrocardiogram forms the basis for diagnosis of ischemia in coronary heart disease. Blood pressure behavior, physical fitness, training heart rate and possible cardiac arrhythmias can additionally be assessed using bicycle ergometry or treadmill testing. When the indications for and contraindications to exercise testing (either bicycle ergometry or treadmill testing) are closely observed, serious complications are rare. However, it is important that the treating physician is aware of and able to recognize possible complications. The present article discusses possible cardiovascular complications and their incidence. PMID- 22086479 TI - [Cost-effectiveness of study nurses in the management of patients with heart failure. A systematic review]. AB - BACKGROUND AND PURPOSE: Heart failure is currently one of the most common and cost-intensive diseases. Furthermore, high morbidity and mortality are distinctive for this disease. Therefore, new treatment programs are increasingly developed; especially the care of heart failure patients by specialized nurses (study nurses) represents a frequent new concept. This review gives a systematic overview of the cost-effectiveness of new treatment concepts with study nurses in comparison to the conventional care of heart failure. METHODS: A systematic literature search in MEDLINE was performed for the period from 1995 till April 2008. The search strategy included terms from three essential areas relating to the working subject: twelve search keys with regard to the clinical picture, 21 words concerning the intervention with study nurses, and 27 terms with reference to health economics. The literature selection was carried out on the basis of a priori defined in- and exclusion criteria. Economic evaluations based on randomized controlled trials with a study duration of at least 6 months which were published in English or German were enclosed. An extraction of the relevant data as well as a qualitative synthesis of information were conducted. RESULTS: A total of 13 studies were identified. With five of nine of the enclosed publications, a statistically significant reduction of the number of all-cause rehospitalizations was reported. Two of twelve publications showed a statistically significant decrease in mortality in favor of the intervention group. Twelve of 13 publications only reported the costs and effects of both groups separately. For the five of nine publications with significant reductions of rehospitalization, an own calculation of the incremental cost-effectiveness ratio (ICER) could be carried out based on the cost and effect data. It turned out an ICER of costs at the rate of 490 Euros up to savings of 7,330 Euros per prevented rehospitalization. CONCLUSION: This systematic review shows an international trend that concepts for the care of patients with heart failure that involve study nurses are cost-effective. For the German context there are no comparable data available. PMID- 22086480 TI - Real-time three-dimensional TEE guidance of a paravalvular mitral valve leak closure procedure. PMID- 22086482 TI - Minds on the blink: the relationship between inattentional blindness and attentional blink. AB - Failures of conscious visual awareness occur when specific task demands prevent an observer from detecting a stimulus that would otherwise be clearly visible. Two examples are inattentional blindness (IB) and attentional blink (AB). IB is the failure to detect an unexpected stimulus when attention is otherwise engaged. AB describes the inability to detect a second target that is presented within 180 500 ms of the first target. Previous research has suggested that similar cognitive processes underlie both IB and AB; however, they are distinct phenomena, and no evidence has directly linked the two. We tested the same group of observers on an IB task and an AB task. Consistent with our hypotheses, we found that "non-noticers" who failed to detect an unexpected stimulus in the IB task also demonstrated a larger AB effect. This suggests that some observers may be more generally susceptible to failures of conscious visual awareness, regardless of specific context. PMID- 22086484 TI - A case of acquired hemophilia A with massive hemothorax. AB - Acquired hemophilia A (AHA) is an uncommon but potentially life-threatening hemorrhagic disorder caused by the development of an inhibitor against coagulation factor VIII (FVIII). AHA is very rare, affecting approximately 1 in 1 million individuals. However, the incidence may actually be higher, because diagnosis is difficult and the disease can be overlooked. We report a case of an 80-year-old man who presented with sudden onset of severe hemothorax. The patient was diagnosed with presumed AHA based on acute onset of bleeding symptoms and unexplained isolated prolonged activated partial thromboplastin time. Diagnosis was definitely established by demonstrating a decrease in FVIII activity, presence of FVIII inhibitor activity, and normal von Willebrand factor. The patient was successfully treated with recombinant activated coagulation factor VII and transcatheter artery embolization of the intercostal arteries. PMID- 22086485 TI - Automatic motion and noise artifact detection in Holter ECG data using empirical mode decomposition and statistical approaches. AB - We present a real-time method for the detection of motion and noise (MN) artifacts, which frequently interferes with accurate rhythm assessment when ECG signals are collected from Holter monitors. Our MN artifact detection approach involves two stages. The first stage involves the use of the first-order intrinsic mode function (F-IMF) from the empirical mode decomposition to isolate the artifacts' dynamics as they are largely concentrated in the higher frequencies. The second stage of our approach uses three statistical measures on the F-IMF time series to look for characteristics of randomness and variability, which are hallmark signatures of MN artifacts: the Shannon entropy, mean, and variance. We then use the receiver-operator characteristics curve on Holter data from 15 healthy subjects to derive threshold values associated with these statistical measures to separate between the clean and MN artifacts' data segments. With threshold values derived from 15 training data sets, we tested our algorithms on 30 additional healthy subjects. Our results show that our algorithms are able to detect the presence of MN artifacts with sensitivity and specificity of 96.63% and 94.73%, respectively. In addition, when we applied our previously developed algorithm for atrial fibrillation (AF) detection on those segments that have been labeled to be free from MN artifacts, the specificity increased from 73.66% to 85.04% without loss of sensitivity (74.48%-74.62%) on six subjects diagnosed with AF. Finally, the computation time was less than 0.2 s using a MATLAB code, indicating that real-time application of the algorithms is possible for Holter monitoring. PMID- 22086486 TI - Endoscope shaft-rigidity control mechanism: "FORGUIDE". AB - Recent developments in flexible endoscopy and other fields of medical technology have raised the need for compact slender shafts that can be made rigid and compliant at will. A novel compact mechanism, named FORGUIDE, with this functionality was developed. The FORGUIDE shaft rigidifies due to friction between a ring of cables situated between a spring and an inflated tube. A mathematical model for the FORGUIDE mechanism working principle was made and used to obtain understanding of this mechanism, predict the maximum rigidity of a FORGUIDE shaft design, and tune its design variables. The mathematical model gave suggestions for significant performance improvement by fine-tuning the design. A prototype FORGUIDE shaft was built and put to a series of bench tests. These tests showed that the FORGUIDE mechanism provides a reliable and simple way to control the rigidity of a flexible shaft. PMID- 22086487 TI - EIT forward problem parallel simulation environment with anisotropic tissue and realistic electrode models. AB - Electrical impedance tomography (EIT) is an imaging technology based on impedance measurements. To retrieve meaningful insights from these measurements, EIT relies on detailed knowledge of the underlying electrical properties of the body. This is obtained from numerical models of current flows therein. The nonhomogeneous and anisotropic electric properties of human tissues make accurate modeling and simulation very challenging, leading to a tradeoff between physical accuracy and technical feasibility, which at present severely limits the capabilities of EIT. This work presents a complete algorithmic flow for an accurate EIT modeling environment featuring high anatomical fidelity with a spatial resolution equal to that provided by an MRI and a novel realistic complete electrode model implementation. At the same time, we demonstrate that current graphics processing unit (GPU)-based platforms provide enough computational power that a domain discretized with five million voxels can be numerically modeled in about 30 s. PMID- 22086488 TI - Integrative deep sequencing of the mouse lung transcriptome reveals differential expression of diverse classes of small RNAs in response to respiratory virus infection. AB - We previously reported widespread differential expression of long non-protein coding RNAs (ncRNAs) in response to virus infection. Here, we expanded the study through small RNA transcriptome sequencing analysis of the host response to both severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza virus infections across four founder mouse strains of the Collaborative Cross, a recombinant inbred mouse resource for mapping complex traits. We observed differential expression of over 200 small RNAs of diverse classes during infection. A majority of identified microRNAs (miRNAs) showed divergent changes in expression across mouse strains with respect to SARS-CoV and influenza virus infections and responded differently to a highly pathogenic reconstructed 1918 virus compared to a minimally pathogenic seasonal influenza virus isolate. Novel insights into miRNA expression changes, including the association with pathogenic outcomes and large differences between in vivo and in vitro experimental systems, were further elucidated by a survey of selected miRNAs across diverse virus infections. The small RNAs identified also included many non-miRNA small RNAs, such as small nucleolar RNAs (snoRNAs), in addition to nonannotated small RNAs. An integrative sequencing analysis of both small RNAs and long transcripts from the same samples showed that the results revealing differential expression of miRNAs during infection were largely due to transcriptional regulation and that the predicted miRNA-mRNA network could modulate global host responses to virus infection in a combinatorial fashion. These findings represent the first integrated sequencing analysis of the response of host small RNAs to virus infection and show that small RNAs are an integrated component of complex networks involved in regulating the host response to infection. IMPORTANCE: Most studies examining the host transcriptional response to infection focus only on protein-coding genes. However, mammalian genomes transcribe many short and long non-protein-coding RNAs (ncRNAs). With the advent of deep-sequencing technologies, systematic transcriptome analysis of the host response, including analysis of ncRNAs of different sizes, is now possible. Using this approach, we recently discovered widespread differential expression of host long (>200 nucleotide [nt]) ncRNAs in response to virus infection. Here, the samples described in the previous report were again used, but we sequenced another fraction of the transcriptome to study very short (about 20 to 30 nt) ncRNAs. We demonstrated that virus infection also altered expression of many short ncRNAs of diverse classes. Putting the results of the two studies together, we show that small RNAs may also play an important role in regulating the host response to virus infection. PMID- 22086489 TI - Assembly of xylanases into designer cellulosomes promotes efficient hydrolysis of the xylan component of a natural recalcitrant cellulosic substrate. AB - In nature, the complex composition and structure of the plant cell wall pose a barrier to enzymatic degradation. Nevertheless, some anaerobic bacteria have evolved for this purpose an intriguing, highly efficient multienzyme complex, the cellulosome, which contains numerous cellulases and hemicellulases. The rod-like cellulose component of the plant cell wall is embedded in a colloidal blend of hemicelluloses, a major component of which is xylan. In order to enhance enzymatic degradation of the xylan component of a natural complex substrate (wheat straw) and to study the synergistic action among different xylanases, we have employed a variation of the designer cellulosome approach by fabricating a tetravalent complex that includes the three endoxylanases of Thermobifida fusca (Xyn10A, Xyn10B, and Xyn11A) and an Xyl43A beta-xylosidase from the same bacterium. Here, we describe the conversion of Xyn10A and Xyl43A to the cellulosomal mode. The incorporation of the Xyl43A enzyme together with the three endoxylanases into a common designer cellulosome served to enhance the level of reducing sugars produced during wheat straw degradation. The enhanced synergistic action of the four xylanases reflected their immediate juxtaposition in the complex, and these tetravalent xylanolytic designer cellulosomes succeeded in degrading significant (~25%) levels of the total xylan component of the wheat straw substrate. The results suggest that the incorporation of xylanases into cellulosome complexes is advantageous for efficient decomposition of recalcitrant cellulosic substrates--a distinction previously reserved for cellulose-degrading enzymes. IMPORTANCE: Xylanases are important enzymes for our society, due to their variety of industrial applications. Together with cellulases and other glycoside hydrolases, xylanases may also provide cost-effective conversion of plant-derived cellulosic biomass into soluble sugars en route to biofuels as an alternative to fossil fuels. Xylanases are commonly found in multienzyme cellulosome complexes, produced by anaerobic bacteria, which are considered to be among the most efficient systems for degradation of cellulosic biomass. Using a designer cellulosome approach, we have incorporated the entire xylanolytic system of the bacterium Thermobifida fusca into defined artificial cellulosome complexes. The combined action of these designer cellulosomes versus that of the wild-type free xylanase system was then compared. Our data demonstrated that xylanolytic designer cellulosomes displayed enhanced synergistic activities on a natural recalcitrant wheat straw substrate and could thus serve in the development of advanced systems for improved degradation of lignocellulosic material. PMID- 22086491 TI - Feasibility and efficacy of an 8-week progressive home-based strengthening exercise program in patients with osteoarthritis of the hip and/or total hip joint replacement: a preliminary trial. AB - The feasibility and efficacy of an additional progressive home-based strengthening exercise program (PHSEP) on subjects that already attended supervised institutional exercise therapy was investigated. Thirty-six hip patients with hip osteoarthritis (OA) and/or total hip replacement in at least one hip joint were randomly assigned to an intervention group (IG) or a control group (CG). IG (18 patients, mean age 64.9, standard deviation (SD) 7.5) followed an 8-week PHSEP in addition to their weekly institutional exercise therapy, while CG (18 patients, mean age 64.7, SD 9) solely continued the weekly institutional exercise sessions. Before and after the intervention period, strength of hip muscles was quantified applying isokinetic concentric and isometric measurements, and health-related quality of life was monitored using the SF36 questionnaire. Adherence to the exercise program was evaluated using exercise logs. The PHSEP was feasible for all subjects in IG with an adherence of 99%. Exercise logs reported that pain resulting from the PHSEP was low. Increased strength in isokinetic concentric hip adduction (13%) and isometric hip abduction (9%), adduction (12%), and flexion (7%) was found in IG in comparison to CG. The results of the SF36 did not change during the intervention period. Consequently, supervised institutional exercise therapy supplemented by a PHSEP could increase hip muscle strength in patients with hip OA and/or total hip replacement. However, further research should evaluate the optimal frequency and duration of such supplementary sessions and their potential to increase physical function and reduce pain. PMID- 22086492 TI - Application of IFT and SPSA to servo system control. AB - This paper treats the application of two data-based model-free gradient-based stochastic optimization techniques, i.e., iterative feedback tuning (IFT) and simultaneous perturbation stochastic approximation (SPSA), to servo system control. The representative case of controlled processes modeled by second-order systems with an integral component is discussed. New IFT and SPSA algorithms are suggested to tune the parameters of the state feedback controllers with an integrator in the linear-quadratic-Gaussian (LQG) problem formulation. An implementation case study concerning the LQG-based design of an angular position controller for a direct current servo system laboratory equipment is included to highlight the pros and cons of IFT and SPSA from an application's point of view. The comparison of IFT and SPSA algorithms is focused on an insight into their implementation. PMID- 22086490 TI - Genome sequencing reveals a phage in Helicobacter pylori. AB - Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population; in a subset of this population, its presence is associated with development of severe disease, such as gastric cancer. Genomic analysis of several strains has revealed an extensive H. pylori pan-genome, likely to grow as more genomes are sampled. Here we describe the draft genome sequence (63 contigs; 26* mean coverage) of H. pylori strain B45, isolated from a patient with gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The major finding was a 24.6 kb prophage integrated in the bacterial genome. The prophage shares most of its genes (22/27) with prophage region II of Helicobacter acinonychis strain Sheeba. After UV treatment of liquid cultures, circular DNA carrying the prophage integrase gene could be detected, and intracellular tailed phage-like particles were observed in H. pylori cells by transmission electron microscopy, indicating that phage production can be induced from the prophage. PCR amplification and sequencing of the integrase gene from 341 H. pylori strains from different geographic regions revealed a high prevalence of the prophage (21.4%). Phylogenetic reconstruction showed four distinct clusters in the integrase gene, three of which tended to be specific for geographic regions. Our study implies that phages may play important roles in the ecology and evolution of H. pylori. IMPORTANCE: Helicobacter pylori chronically infects the gastric mucosa in more than half of the human population, and while most of the infected individuals do not develop disease, H. pylori infection doubles the risk of developing gastric cancer. An abundance and diversity of viruses (phages) infect microbial populations in most environments and are important mediators of microbial diversity. Our finding of a 24.6-kb prophage integrated inside an H. pylori genome and the observation of circular integrase gene-containing DNA and phage like particles inside cells upon UV treatment demonstrate that we have discovered a viable H. pylori phage. The additional finding of integrase genes in a large proportion of screened isolates of diverse geographic origins indicates that the prevalence of prophages may have been underestimated in H. pylori. Since phages are important drivers of microbial evolution, the discovery should be important for understanding and predicting genetic diversity in H. pylori. PMID- 22086494 TI - Manual matching of perceived surface orientation is affected by arm posture: evidence of calibration between proprioception and visual experience in near space. AB - Proprioception of hand orientation (orientation production using the hand) is compared with manual matching of visual orientation (visual surface matching using the hand) in two experiments. In experiment 1, using self-selected arm postures, the proportions of wrist and elbow flexion spontaneously used to orient the pitch of the hand (20 and 80%, respectively) are relatively similar across both manual matching tasks and manual orientation production tasks for most participants. Proprioceptive error closely matched perceptual biases previously reported for visual orientation perception, suggesting calibration of proprioception to visual biases. A minority of participants, who attempted to use primarily wrist flexion while holding the forearm horizontal, performed poorly at the manual matching task, consistent with proprioceptive error caused by biomechanical constraints of their self-selected posture. In experiment 2, postural choices were constrained to primarily wrist or elbow flexion without imposing biomechanical constraints (using a raised forearm). Identical relative offsets were found between the two constraint groups in manual matching and manual orientation production. The results support two claims: (1) manual orientation matching to visual surfaces is based on manual proprioception and (2) calibration between visual and proprioceptive experiences guarantees relatively accurate manual matching for surfaces within reach, despite systematic visual biases in perceived surface orientation. PMID- 22086493 TI - Roles of amyloid precursor protein family members in neuroprotection, stress signaling and aging. AB - The roles of amyloid precursor protein (APP) family members in normal brain function are poorly understood. Under physiological conditions the majority of APP appears to be processed along the non-amyloidogenic pathway leading to the formation of the secreted N-terminal APP fragment sAPPalpha. This cleavage product of APP has been implicated in several physiological processes such as neuroprotection, synaptic plasticity, neurite outgrowth and synaptogenesis. In this review we focus on the role of APP family members in neuroprotection and summarize the cellular and molecular mechanisms which are believed to mediate this effect. We propose that a reduction of APP processing along the non amyloidogenic pathway during brain aging could result in an enhanced susceptibility of neurons to cellular stress and could contribute to neurodegeneration in Alzheimer's disease. PMID- 22086495 TI - On the opportunistic nature of transcription and replication initiation in the metazoan genome. AB - Cellular identity and its response to external or internal signalling variations are encoded in a cell's genome as regulatory information. The genomic regions that specify this type of information are highly variable and degenerated in their sequence determinants, as it is becoming increasingly evident through the application of genome-scale methods to study gene expression. Here, we speculate that the same scenario applies to the regulatory regions controlling where DNA replication starts in the metazoan genome. We propose that replication origins cannot be defined as unique genomic features, but rather that DNA synthesis initiates opportunistically from accessible DNA sites, making cells highly robust and adaptable to environmental or developmental changes. PMID- 22086496 TI - Assessment of the transforming potential of novel anaplastic lymphoma kinase point mutants. AB - Anaplastic lymphoma kinase (ALK) has emerged as an important oncogene in a number of human malignancies ranging from non-Hodgkin lymphoma to neuroblastoma. In the former case, ALK is activated as a consequence of a chromosomal translocation and in the latter due to point mutations. In both cases the transforming potential of these oncogenic forms of ALK have been shown in vitro employing traditional cellular transformation assays including 3T3 foci formation. We reasoned that other ALK mutants which have been identified by the Cancer Genome Project may likewise possess transformation potential. We have selected seven ALK mutants identified in cell lines representative of a variety of human cancers based on position within the ALK protein, zygosity and frequency of detection including R1192Q, K1525E, C1021Y, R412C, A1252V, D1311A, K1518N and have compared their transformation capability in comparison to the published neuroblastoma-associated F1174L ALK mutant when expressed in immortalized p53(-/-) murine embryonic fibroblasts. Whilst the F1174L mutant reproducibly drives foci formation in vitro, the other ALK mutants fail in this task. Furthermore, apart from the F1174L ALK mutant, the ALK protein is not phosphorylated on tyrosine residue 1604 suggesting that they are kinase-inactive in this cellular context. We conclude that not all ALK mutants have transformation potential and may represent "passenger" mutations in the evolution of cancer. PMID- 22086497 TI - Inappropriate and excessive guilt: instrument validation and developmental differences in relation to depression. AB - Inappropriate or excessive guilt is listed as a symptom of depression by the American Psychiatric Association (1994). Although many measures of guilt have been developed, definitional and operational problems exist, especially in the application of such measures in childhood and adolescence. To address these problems, the current study introduces the Inappropriate and Excessive Guilt Scale (IEGS), assesses its validity for use with children and adolescents, and tests its relation to depression across development. From a sample of 370 children between 7 and 16 years old, results provided (1) evidence that items designed to assess inappropriate and excessive guilt converged onto a single underlying factor, (2) support for the convergent, discriminant, and construct validity of the IEGS in a general youth population, and (3) evidence of incremental validity of the IEGS over-and-above other measures of guilt. Results also supported the hypothesis that inappropriate and excessive guilt as well as negative cognitive errors become less normative and more depressotypic with age. PMID- 22086498 TI - Flexible planar microfluidic chip employing a light emitting diode and a PIN photodiode for portable flow cytometers. AB - Detection of fluorescence particles is a key method of flow cytometry. We evaluate the performance of a design for a microfluidic fluorescence particle detection device. Due to the planar design with low layer thicknesses, we avoid optical components such as lenses or dichroic mirrors and substitute them with a shadow mask and colored film filters. A commercially available LED is used as the light source and a PIN-photodiode as detector. This design approach reduces component cost and power consumption and enables supplying the device with power from a standard USB port. From evaluation of this design, we obtain a maximum particle detection frequency of up to 600 particles per second at a sensitivity of better than 4.7 * 10(5) MESF (molecules of equivalent soluble fluorochrome) measured with particles for FITC sensitivity calibration. Lowering the flow rate increases the instrument sensitivity by an order of magnitude enabling the detection of particles with 4.5 * 10(4) MESF. PMID- 22086499 TI - Freiburg neuropathology case conference: cystic mass lesions of the temporal and occipital lobes in an elderly patient. PMID- 22086500 TI - JUDOCA: junction detection operator based on circumferential anchors. AB - In this paper, we propose an edge-based junction detector. In addition to detecting the locations of junctions, this operator specifies their orientations as well. In this respect, a junction is defined as a meeting point of two or more ridges in the gradient domain into which an image can be transformed through Gaussian derivative filters. To accelerate the detection process, two binary edge maps are produced; a thick-edge map is obtained by imposing a threshold on the gradient magnitude image, and another thin-edge map is obtained by calculating the local maxima. Circular masks are centered at putative junctions in the thick edge map, and the so-called circumferential anchors or CA points are detected in the thin map. Radial lines are scanned to determine the presence of junctions. Comparisons are made with other well-known detectors. This paper proposes a new formula for measuring the detection accuracy. In addition, the so-called junction coordinate systems are introduced. Our operator has been successfully used to solve many problems such as wide-baseline matching, 3-D reconstruction, camera parameter enhancing, and indoor and obstacle localization. PMID- 22086501 TI - Rotation-invariant image and video description with local binary pattern features. AB - In this paper, we propose a novel approach to compute rotation-invariant features from histograms of local noninvariant patterns. We apply this approach to both static and dynamic local binary pattern (LBP) descriptors. For static-texture description, we present LBP histogram Fourier (LBP-HF) features, and for dynamic texture recognition, we present two rotation-invariant descriptors computed from the LBPs from three orthogonal planes (LBP-TOP) features in the spatiotemporal domain. LBP-HF is a novel rotation-invariant image descriptor computed from discrete Fourier transforms of LBP histograms. The approach can be also generalized to embed any uniform features into this framework, and combining the supplementary information, e.g., sign and magnitude components of the LBP, together can improve the description ability. Moreover, two variants of rotation invariant descriptors are proposed to the LBP-TOP, which is an effective descriptor for dynamic-texture recognition, as shown by its recent success in different application problems, but it is not rotation invariant. In the experiments, it is shown that the LBP-HF and its extensions outperform noninvariant and earlier versions of the rotation-invariant LBP in the rotation invariant texture classification. In experiments on two dynamic-texture databases with rotations or view variations, the proposed video features can effectively deal with rotation variations of dynamic textures (DTs). They also are robust with respect to changes in viewpoint, outperforming recent methods proposed for view-invariant recognition of DTs. PMID- 22086502 TI - Spectral-spatial classification of hyperspectral data based on a stochastic minimum spanning forest approach. AB - In this paper, a new method for supervised hyperspectral data classification is proposed. In particular, the notion of stochastic minimum spanning forest (MSF) is introduced. For a given hyperspectral image, a pixelwise classification is first performed. From this classification map, M marker maps are generated by randomly selecting pixels and labeling them as markers for the construction of MSFs. The next step consists in building an MSF from each of the M marker maps. Finally, all the M realizations are aggregated with a maximum vote decision rule in order to build the final classification map. The proposed method is tested on three different data sets of hyperspectral airborne images with different resolutions and contexts. The influences of the number of markers and of the number of realizations M on the results are investigated in experiments. The performance of the proposed method is compared to several classification techniques (both pixelwise and spectral-spatial) using standard quantitative criteria and visual qualitative evaluation. PMID- 22086503 TI - Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma. AB - BACKGROUND: The aim of this study was to evaluate the expression of epidermal growth factor receptor (EGFR) and insulinlike growth factor 1 receptor (IGF-1R) proteins and IGF-1R gene copy numbers in pancreatic ductal adenocarcinoma in relation to patients' characteristics and prognosis. METHODS: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue derived from tumor specimens recovered during surgery. Slides were evaluated for membranous EGFR and IGF-1R staining using both the HercepTest and the semiquantitative H score systems. Chromogenic in situ hybridization was performed to quantify IGF-1R gene copy number. The primary outcome was the association between EGFR expression, IGF-1R expression-in both neoplastic epithelial and stromal cells-or IGF-1R gene copy number and overall survival. Secondary outcomes included associations between EFGR and IGF-1R expression and pathologic variables. RESULTS: A total of 105 patients were included. EGFR expression was present in 30.4% of cases and was associated with lymph node metastasis (P = .038). IGF-1R was overexpressed in 53% of tumors and correlated with higher tumor grade (P = .033). High membranous expression of EGFR (P < .001) and/or IGF-1R (P = .004), the cytoplasmic detection of EGFR (P = .027), and high expression levels of IGF 1R in the tumoral stroma (P < .001) were all associated with shorter overall survival, being significantly better in patients who simultaneously do not express membranous EGFR or stromal IGF-1R. CONCLUSIONS: EGFR and IGF-1R expression, in neoplastic and stromal cells, seems to be an important prognostic factor. PMID- 22086504 TI - Eggplant mild leaf mottle virus (EMLMV), a new putative member of the genus Ipomovirus that harbors an HC-Pro gene. AB - Since 2003, a new viral disease of eggplant (Solanum melongena L.) has been spreading in fields in the Jordan and Arava Valleys, Israel. The symptoms of this disease include mild leaf mottling and varying degrees of fruit distortion. This disease can be transmitted by mechanical sap inoculation, as well as by the whitefly Bemisia tabaci (Homoptera, Aleyrodidae) and has been tentatively named eggplant mild leaf mottle virus (EMLMV). Our study aimed to determine the complete sequence and genome organization of EMLMV. The extracted viral RNA was subjected to SOLiD next-generation sequence analysis and used as a template for reverse transcription synthesis, which was followed by ds-cDNA synthesis or PCR amplification. The ssRNA genome of EMLMV includes 9,280 nucleotides, excluding a 3' terminal poly-adenylated tail. The genome includes a putative single, large open reading frame (ORF) that encodes a polyprotein of 3,011 amino acids, a short overlapping ORF of PIPO protein comprised of 71 amino acids and 5' and 3' non coding regions of 108 and 136 nucleotides, respectively. The deduced amino acid sequence of the EMLMV polyprotein is relatively close to that of sweet potato mild mottle virus (SPMMV), with 37% shared sequence identity. Among the four ipomoviruses, only SPMMV and the putative genus member EMLMV contain a helper component-proteinase (HC-Pro) gene. Like SPMMV-HC-Pro, EMLMV-HC-Pro also contains the highly conserved PTK domain that is thought to be involved in the aphid assisted transmission of potyviruses. PMID- 22086505 TI - Evolutionary analysis of human-origin influenza A virus (H3N2) genes associated with the codon usage patterns since 1993. AB - This study investigated genetic variations in eight major genes (hemagglutinin, HA; neuraminidase, NA; matrix protein, MP; non-structural protein, NS; nucleoprotein, NP; polymerase, PA; PA basic protein 1, PB1; and PA basic protein 2, PB2) of the influenza A virus subtype H3N2 (A/H3N2) to determine the evolutionary pattern in codon bias. A total of 6,881 sequences isolated between 1993 and 2010 were used. The relative synonymous codon usage (RSCU) and G+C% content at the three codon positions were analyzed by calculating the codon substitution patterns were analyzed by calculating the percentage of synonymously substituted codons (SSCs) and that of codons substituted to the same codon within each synonymous codon group (EMC) between 1993 and subsequent years. In the multivariate analysis of RSCU, we observed directional changes in HA, NA, PB1, and PB2, and these changes were significantly correlated with the variation in the G+C contents at the first (GC(1st)) and second (GC(2nd)) codon positions over time. These directional changes in HA and NA appear to affect their antigenic characteristics by altering their SSCs gradually, and NP, PA, PB1, and PB2 genes also continuously changed their substitution patterns by accumulating the decrements of EMC values over a long term. Our findings suggest that, in human populations, A/H3N2 viruses have gradually changed their SSCs in two external genes, HA and NA, and that these accumulated alteration patterns may result in the antigenic changes over time. Moreover, A/H3N2 viruses also appear to change synonymous codon usage patterns in NP, PA, PB1, and PB2 genes by accumulating decrements in EMCs within synonymous codon groups over time. PMID- 22086506 TI - Complications in brief: Anterior cruciate ligament reconstruction. AB - When performing reconstruction of the ACL, the major complications that can arise include missed concomitant injuries, tunnel malposition, patellar fracture, knee stiffness, and infection. We review the complications that can occur as a result of errors made before, during, and after surgery. PMID- 22086507 TI - Combined anterior-posterior surgery is the most important risk factor for developing proximal junctional kyphosis in idiopathic scoliosis. AB - BACKGROUND: Several studies have identified risk factors for proximal junctional kyphosis (PJK) after instrumentation for scoliosis, but the relative risks are unclear. QUESTIONS/PURPOSES: We identified risk factors for PJK in idiopathic scoliosis and determined their relative risks in a predictive model. METHODS: We retrospectively reviewed the charts of all 249 patients with idiopathic scoliosis who underwent surgery from 1996 to 2008. We compared those who developed PJK to those who did not. We identified risk factors for PJK and performed univariate and multivariate analyses to determine independent risk factors. We then used a Cox proportional-hazards model to evaluate the time to the development of PJK. The minimum followup time was 1.5 years (mean, 4 years; range, 1.5-9 years). RESULTS: The incidence of PJK in our series of patients with idiopathic scoliosis was 17%. There was no difference in Scoliosis Research Society-22 scores between patients without and with junctional kyphosis. Independent risk factors included proximal fusion to T1 through T3 and sagittal sacral vertical line, while in the Cox model a combined anterior-posterior approach surgery was the most important risk factor. CONCLUSIONS: Patients with a T1 through T3 upper instrumented level, combined anterior-posterior surgery, and increased sagittal sacral vertical line difference had a higher likelihood of developing PJK. Of these risk factors, anterior-posterior surgery was the strongest risk factor. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22086508 TI - Roles of neuronal nitric oxide synthase, oxidative stress, and propofol in N methyl-D-aspartate-induced dilatation of cerebral arterioles. AB - BACKGROUND: It remains unclear whether N-methyl-D-aspartate (NMDA) receptors contribute to cerebral parenchymal vasodilatation, and any effects of clinically used anaesthetics on the dilatation. The present study was designed to examine whether NMDA induces neuronal nitric oxide synthase (NOS)-mediated dilatation, in the cerebral parenchymal arterioles, and whether propofol and superoxide modulate the dilatation in relation to the NMDA receptor activation. METHODS: The cerebral parenchymal arterioles within rat brain slices were monitored by a computer assisted microscopy, and the vasodilatation in response to NMDA (10(-7) to 10(-5) M) was evaluated. Immunofluorescence analysis to neuronal and endothelial NOS and measurement of levels of superoxide and nitric oxide within the arteriole were simultaneously performed. RESULTS: Propofol, an NMDA receptor antagonist MK801, and a neuronal NOS antagonist S-methyl-l-thiocitrulline (SMTC) reduced NMDA induced dilation, whereas a superoxide inhibitor, Tiron, and NADPH oxidase inhibitor, gp91ds-tat, augmented NMDA-induced dilatation. Immunofluorescence analysis revealed distribution of neuronal NOS in both endothelial and smooth muscle cells in addition to neuronal cells. NMDA-induced superoxide and nitric oxide within the parenchymal arterioles. The increased superoxide within the arteriole was similarly inhibited by MK801, SMTC, gp91ds-tat, propofol, and a neuronal NOS antagonist vinyl-l-NIO, whereas the level of nitric oxide was reduced by MK801, SMTC, propofol, and vinyl-l-NIO, and it was augmented by gp91ds tat. CONCLUSIONS: NMDA dilates cerebral parenchymal arterioles possibly via neuronal NOS activation, whereas it produces superoxide via NADPH oxidase. In these arterioles, propofol reduces both the dilatation and superoxide production in response to NMDA. PMID- 22086509 TI - Comparison of thromboelastometry (ROTEM(r)) with standard plasmatic coagulation testing in paediatric surgery. AB - BACKGROUND: Thromboelastometry (ROTEM((r))) might be useful to detect intraoperative coagulation disorders early in major paediatric surgery. This observational trial compares this technique to standard coagulation tests. METHODS: Intraoperative blood sampling was obtained in children undergoing elective major surgery. At each time point, standard coagulation tests [activated partial thromboplastin time (aPTT), prothrombin time (PT), and fibrinogen level] and ROTEM((r)) analyses (InTEM, ExTEM, and FibTEM) were performed simultaneously by trained hospital laboratory staff. RESULTS: A total of 288 blood samples from 50 subjects were analysed. While there was a poor correlation between PT and aPTT to ExTEM clotting time (CT) and InTEM CT, respectively, a good correlation was detected between PT and aPTT to clot formation time, and a very good correlation between fibrinogen level and FibTEM assay (r=0.882, P<0.001). Notably, 64% of PT and 94% of aPTT measurements were outside the reference range, while impaired CT was observed in 13% and 6.3%, respectively. Standard coagulation test results were available after a median of 53 min [inter-quartile range (IQR): 45-63 min], whereas 10 min values of ROTEM((r)) results were available online after 23 min (IQR: 21-24 min). CONCLUSIONS: PT and aPTT cannot be interchangeably used with ROTEM((r)) CT. Based on the results of ROTEM((r)), recommended thresholds for PT and aPTT might overestimate the need for coagulation therapy. A good correlation was found between the fibrinogen level and the FibTEM assay. In addition, ROTEM((r)) offered faster turnaround times. PMID- 22086510 TI - Randomized, prospective, observational simulation study comparing residents' needle-guided vs free-hand ultrasound techniques for central venous catheter access. AB - BACKGROUND: Short-axis ultrasound-guided placement of central venous catheters (CVCs) is widely accepted as safe practice. However, utilizing the long-axis approach could further improve safety, as it allows for better visualization of the needle as it is advanced to the target vessel. However, the long-axis approach has not widely been used due to the technical difficulty. Recently, a new needle guidance device has become available to aid in the long-axis approach. We hypothesized that the use of a needle guide paired with the long-axis approach would facilitate puncture of the target vessel in a simulation model more effectively than similar free-hand techniques. METHODS: A prospective observational study of anaesthesia residents using a CVC partial-task training device was conducted. Each resident performed needle puncture of the target vessel with three different techniques, assigned in random order: short-axis free hand (S-FH), long-axis free hand (L-FH), and long-axis needle guide (NG). To prove the effectiveness of the needle guide, the fraction of time the needle tip remained in view of the ultrasound was recorded and compared. Time required for completing the task and the number of needle sticks and needle re-directions were compared. RESULTS: Thirty-three residents participated in the study. The fraction of time the needle tip remained in view of the ultrasound was significantly higher for the residents using NG [0.90 (0.10)] compared with residents using the other techniques [L-FH: 0.36 (0.20), S-FH: 0.18 (0.10)] (P<0.001). For each resident, the use of the needle guide in the long-axis approach increased visualization by 352 (276)% compared with that of L-FH and by 1028 (1804) % compared with that of S-FH. There was no significant difference in time required to puncture the target between NG [23.7 (14.6) s] and L-FH [30.3 (36.5) s] (P=0.21); however, both were significantly longer than S-FH [17.0 (13.3) s] (P=0.012). The numbers of needle sticks and of needle re-directions did not differ among the groups. CONCLUSIONS: The needle guide device used in the long axis approach improved the needle visualization compared with free-hand techniques. The needle guide used in the long-axis technique, however, did not facilitate puncture of the target vessel in this simulation model when compared with free-hand techniques. PMID- 22086511 TI - Elevated vancomycin trough is not associated with nephrotoxicity among inpatient veterans. AB - BACKGROUND: Vancomycin troughs of 15-20 mg/L are recommended in the treatment of invasive staphylococcal disease, higher levels than previously recommended. OBJECTIVE/SETTING: We sought to determine if there was an association between vancomycin trough and nephrotoxicity, defined as 0.5 mg/L or 50% increase in serum creatinine, at a large Veterans Affairs medical center. PATIENTS AND METHODS: We reviewed records of 348 inpatients at our institution who received >=5 days of vancomycin during 2 time periods when vancomycin dosing protocols differed (May 2005-April 2006 and January 2007-December 2007). Potential risk factors for nephrotoxicity were collected prior to nephrotoxicity onset, and all patients with nephrotoxicity events occurring within 5 days of starting vancomycin were excluded. RESULTS: Overall incidence of nephrotoxicity was 31/348 patients (8.9%). A similar percentage of patients experienced nephrotoxicity in 2005-2006 versus 2007 (16/201 vs 15/147, respectively; P = 0.57), despite a rise in mean (9.7 mg/L in 2005-2006 vs 13.2 mg/L in 2007; P < 0.0001) and highest (11.8 mg/L in 2005-2006 vs 15.7 mg/L in 2007; P < 0.0001) vancomycin trough levels achieved. In a multivariate logistic regression model, only receipt of intravenous contrast dye was significantly associated with nephrotoxicity (OR 4.01, P < 0.001), though there was a trend toward an association between maximum vancomycin trough >=15 mg/L and nephrotoxicity (OR 2.05, P = 0.082). Overall reversibility of nephrotoxicity either prior to or within 72 hours of vancomycin discontinuation was 77.8%. CONCLUSIONS: We conclude that nephrotoxicity, with higher trough levels occurring at >=5 days of vancomycin therapy, was uncommon at our institution and typically reversible. PMID- 22086512 TI - PROP1 and CTNNB1 expression in adamantinomatous craniopharyngiomas with or without beta-catenin mutations. AB - INTRODUCTION: Activating mutations in exon 3 of the beta-catenin gene are involved in the pathogenesis of adamantinomatous craniopharyngiomas. Recently, the interaction between beta-catenin and PROP1 has been shown to be responsible for pituitary cell lineage determination. We hypothesized that dysregulated PROP1 expression could also be involved in the pathogenesis of craniopharyngiomas OBJECTIVES: To determine whether dysregulated gene expression was responsible for tumor pathogenesis in adamantinomatous craniopharyngiomas, the beta-catenin gene was screened for mutations, and the expression of the beta-catenin gene and PROP1 was evaluated. beta-catenin gene was amplified and sequenced from 14 samples of adamantinomatous craniopharyngiomas. PROP1 and beta-catenin gene expression was assessed by real-time RT-PCR from 12 samples, and beta-catenin immunohistochemistry was performed on 11 samples. RESULTS: Mutations in the beta catenin gene were identified in 64% of the adamantinomatous craniopharyngiomas samples. Evidence of beta-catenin gene overexpression was found in 71% of the tumors with beta-catenin mutations and in 40% of the tumors without mutations, and beta-catenin immunohistochemistry revealed a nuclear staining pattern for each of the analyzed samples. PROP1 expression was undetectable in all of the tumor samples. CONCLUSION: We found evidence of beta-catenin gene overexpression in the majority of adamantinomatous craniopharyngiomas, and we also detected a nuclear beta-catenin staining pattern regardless of the presence of a beta catenin gene mutation. These results suggest that WNT signaling activation plays an important role in the pathogenesis of adamantinomatous craniopharyngiomas. Additionally, this study was the first to evaluate PROP1 expression in adamantinomatous craniopharyngiomas, and the absence of PROP1 expression indicates that this gene is not involved in the pathogenesis of this tumor, at least in this cohort. PMID- 22086513 TI - Autologous stem cell transplantation improves quality of life in economically challenged, Brazilian multiple myeloma patients. AB - OBJECTIVES: 1) To characterize the impact of multiple myeloma on the quality of life of patients treated in two public institutions in Sao Paulo State, Brazil, using a generic Short Form 36 Health Survey and a questionnaire specific for oncologic patients (QLQ-C30) upon diagnosis, after the clinical treatment, and at day +100 after autologous stem cell transplantation; 2) to evaluate whether autologous stem cell transplantation can improve the quality of life of our economically challenged population aside from providing a clinical benefit and disease control. METHODS: We evaluated 49 patients with multiple myeloma (a total of 70 interviews) using the two questionnaires. The scores upon diagnosis, post treatment/pre-autologous stem cell transplantation, and at D+100 were compared using ANOVA (a comparison of the three groups), post hoc tests (two-by-two comparisons of the three groups), and paired t-tests (the same case at two different times). RESULTS: Of the included patients, 87.8% had a family budget under US $600 (economic class C, D, or E) per month. The generic Short Form 36 Health Survey questionnaire demonstrated that physical function, role-physical, and bodily pain indices were statistically different across all three groups, favoring the D+100 autologous stem cell transplantation group (ANOVA). The questionnaire specific for oncologic patients, the QLQ-C30 questionnaire, confirmed what had been demonstrated by the Short Form 36 Health Survey with respect to physical function and bodily pain, with improvements in role functioning, fatigue, and lack of appetite and constipation, favoring the D+100 autologous stem cell transplant group (ANOVA). The post hoc tests and paired t tests confirmed a better outcome after autologous stem cell transplantation CONCLUSION: The questionnaire specific for cancer patients seems to be more informative than the generic Short Form 36 Health Survey questionnaire and reflects the real benefit of autologous stem cell transplantation in the quality of life of multiple myeloma patients in two public Brazilian institutions that provide assistance for economically challenged patients. PMID- 22086514 TI - Association between participation in community groups and being more physically active among older adults from Florianopolis, Brazil. AB - OBJECTIVE: In Brazil, older adults frequently participate in community groups. However, the influence of this participation on physical activity levels has not been fully investigated. It is known that both regular physical activity and social support are beneficial for health. The aim of this study is to evaluate the association between participation in community groups and physical activity among older adults from Florianopolis, Brazil. METHODS: The sample consisted of 1062 adults with a mean age of 71.9 (+/-7.6) years. Among these individuals, 293 subjects participated in community groups and 769 did not. A questionnaire to collect sociodemographic data and the long version of the International Physical Activity Questionnaire were used for the assessment. RESULTS: The prevalence of active older adults was 66.6% among participants in community groups and 58.4% among non-participants. Participation in these groups was significantly associated with being more physically active in the transportation and domestic domains, but with being less physically active in the leisure-time domain. Some changes in these associations were observed when the sample was stratified by age, gender, body mass index, and health status. With respect to total physical activity, participation in community groups was associated with being more physically active in only two strata (subjects younger than 70 years and women). CONCLUSION: The results of this study indicate that older adults who participate in community groups are characterized by a greater probability of being more physically active. However, longitudinal studies are needed to determine whether participation in community groups facilitates the adoption of physically active behavior. PMID- 22086515 TI - Gender differences, polypharmacy, and potential pharmacological interactions in the elderly. AB - OBJECTIVE: This study aims to analyze pharmacological interactions among drugs taken by elderly patients and their age and gender differences in a population from Porto Alegre, Brazil. METHODS: We retrospectively analyzed the database provided by the Institute of Geriatric and Gerontology, Porto Alegre, Brazil. The database was composed of 438 elderly and includes information about the patients' disease, therapy regimens, utilized drugs. All drugs reported by the elderly patients were classified using the Anatomical Therapeutic and Chemical Classification System. The drug-drug interactions and their severity were assessed using the Micromedex(r) Healthcare Series. RESULTS: Of the 438 elderly patients in the data base, 376 (85.8%) used pharmacotherapy, 274 were female, and 90.4% of females used drugs. The average number of drugs used by each individual younger than 80 years was 3.2+/-2.6. Women younger than 80 years old used more drugs than men in the same age group whereas men older than 80 years increased their use of drugs in relation to other age groups. Therefore, 32.6% of men and 49.2% of women described at least one interaction, and 8.1% of men and 10.6% of women described four or more potential drug-drug interactions. Two-thirds of drug drug interactions were moderate in both genders, and most of them involved angiotensin-converting enzyme inhibitor, non-steroidal anti-inflammatory, loop and thiazide diuretics, and beta-blockers. CONCLUSION: Elderly patients should be closely monitored, based on drug class, gender, age group and nutritional status. PMID- 22086516 TI - Non-small cell lung cancer in never smokers: a clinical entity to be identified. AB - OBJECTIVES: It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among never-smokers with non-small cell lung cancer. METHODS: All consecutive non-small cell lung cancer patients diagnosed (n = 285) between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current) were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable), gender (female vs. male), smoking status (never- vs. ever-smoker), the Karnofsky Performance Status Scale (continuous variable), histological type (adenocarcinoma vs. non-adenocarcinoma), AJCC staging (early vs. advanced staging), and treatment (chemotherapy and/or radiotherapy vs. the best treatment support). RESULTS: Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32%) and have adenocarcinoma (70% vs. 51%). Overall median survival was 15.7 months (95% CI: 13.2 to 18.2). The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. CONCLUSIONS: Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type. PMID- 22086517 TI - M2-polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma. AB - OBJECTIVES: Tumor-associated macrophages have been implicated in promoting tumor growth, progression and metastasis. However, the activated phenotype (M1 or M2) of tumor-associated macrophages remains unknown in solid tumors. Therefore, this study examined the density and prognostic significance of M2-polarized tumor associated macrophages in lung adenocarcinoma. METHODS: Tumor specimens from 65 lung adenocarcinoma patients were assessed by ELISA for Th1/Th2 cytokine concentrations. The activated phenotype (M1 or M2) of tumor-associated macrophages was determined utilizing immunofluorescence staining. Additionally, to evaluate lymphangiogenesis, peritumoral lymphatic microvessel density was measured using D2-40. The correlation between tumor-associated macrophage subtype and overall patient survival was analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A shift toward Th2 cytokine expression was detected within lung adenocarcinoma microenvironments. Approximately 79.71+/ 16.27% of tumor-associated macrophages were M2 polarized; the remaining 20.35+/ 5.31% were M1 polarized. The infiltration of M2-polarized macrophages was significantly associated with P-TNM staging and lymph node metastasis. The peritumoral lymphatic microvessel density was significantly higher in the high M2 polarized tumor-associated macrophage group than in the low M2-polarized tumor associated macrophage group. A significant difference in overall patient survival was detected not only between patients with tumors with high and low macrophage counts but also between patients with tumors with high and low counts of M2 polarized macrophages. CONCLUSION: Tumor-associated macrophages in lung adenocarcinoma have an M2-polarized subtype and are associated with poor prognoses, perhaps resulting from accelerated lymphangiogenesis and lymph node metastasis. PMID- 22086518 TI - A negative expiratory pressure test during wakefulness for evaluating the risk of obstructive sleep apnea in patients referred for sleep studies. AB - OBJECTIVE: Obstructive sleep apnea is characterized by increased upper airway collapsibility during sleep. The present study investigated the use of the negative expiratory pressure test as a method to rule out obstructive sleep apnea. METHODS: Flow limitation was evaluated in 155 subjects. All subjects underwent a diurnal negative expiratory pressure test and a nocturnal sleep study. The severity of sleep apnea was determined based on the apnea-hypopnea index. Flow limitation was assessed by computing the exhaled volume at 0.2, 0.5, and 1.0 s (V0.2, V0.5, and V1.0, respectively) during the application of a negative expiratory pressure and expressed as a percentage of the previous exhaled volume. Receiver-operating characteristic curves were constructed to identify the optimal threshold volume at 0.2, 0.5, and 1.0 s for obstructive sleep apnea detection. RESULTS: Mean expiratory volumes at 0.2 and 0.5 s were statistically higher (p <0.01) in healthy subjects than in all obstructive sleep apneic groups. Increasing disease severity was associated with lower expiratory volumes. The V0.2 (%) predictive parameters for the detection of sleep apnea were sensitivity (81.1%), specificity (93.1%), PPV (98.1%), and NPV (52.9%). Sensitivity and NPV were 96.9% and 93.2%, respectively, for moderate-to-severe obstructive sleep apnea, and both were 100% for severe obstructive sleep apnea. CONCLUSION: Flow limitation measurement by V 0.2 (%) during wakefulness may be a very reliable method to identify obstructive sleep apnea when the test is positive and could reliably exclude moderate and severe obstructive sleep apnea when the test is negative. The negative expiratory pressure test appears to be a useful screening test for suspected obstructive sleep apnea. PMID- 22086519 TI - The characteristics of stress cardiomyopathy in an ethnically heterogeneous population. AB - OBJECTIVES: Stress cardiomyopathy is a cardiac syndrome that is characterized by transient left ventricular systolic dysfunction in the absence of obstructive coronary artery disease. Its epidemiology has been described in homogeneous Asian, Caucasian and Black populations, but its characteristics in heterogeneous populations are poorly understood. Our aim was to assess the characteristics of stress cardiomyopathy in a heterogeneous population that included a large percentage of Hispanics. METHODS: We reviewed 59 consecutive cases of stress cardiomyopathy that were confirmed by coronary angiography and were in agreement with the Mayo Clinic diagnostic criteria. RESULTS: The mean age of the patients was 74 years (range, 39-91 years), and 37 patients were female (62.7%). Twenty nine patients (49.2%) were Latino/Hispanic, 26 (44%) were Caucasian, 3 (5%) were Asian, and 1 patient (1.7%) was Black. The most common chief symptom was dyspnea, followed by chest pain and an absence of symptoms in 54.2, 28.8, and 18.6% of the patients, respectively. The primary EKG abnormalities consisted of a T wave inversion, an ST segment elevation, and ST segment depression in 69.5%, 25.4%, and 15.3% of the patients, respectively. The stressor event was identified in 90% of the cases. In 32 cases (54%), the stressor event was physical stress or a medical illness, and in 21 cases (35.6%), the stressor event was emotional stress. The in-hospital mortality rate was 8.5%. CONCLUSIONS: In our heterogeneous study population, stress cardiomyopathy presented with a 3:2 female to-male ratio, and dyspnea was the most common chief complaint. Stress cardiomyopathy exhibited a T wave inversion as the primary EKG abnormality. These findings differ from previous cases that have been reported, and further studies are needed. PMID- 22086520 TI - Preoperative nodal staging of non-small cell lung cancer using 99mTc-sestamibi spect/ct imaging. AB - OBJECTIVES: The proper nodal staging of non-small cell lung cancer is important for choosing the best treatment modality. Although computed tomography remains the first-line imaging test for the primary staging of lung cancer, its limitations for mediastinum nodal staging are well known. The aim of this study is to evaluate the accuracy of hybrid single-photon emission computed tomography and computed tomography using 99mTc-sestamibi in the nodal staging of patients with non-small cell lung cancer and to identify potential candidates for surgical treatment. METHODS: Prospective data were collected for 41 patients from December 2006 to February 2009. The patients underwent chest computed tomography and single-photon emission computed tomography/computed tomography examinations with 99mTc-sestamibi within a 30-day time period before surgery. Single-photon emission computed tomography/computed tomography was considered positive when there was focal uptake of sestamibi in the mediastinum, and computed tomography scan when there was lymph nodes larger than 10 mm in short axis. The results of single-photon emission computed tomography and computed tomography were correlated with pathology findings after surgery. RESULTS: Single-photon emission computed tomography/computed tomography correctly identified six out of 19 cases involving hilar lymph nodes and one out of seven cases involving nodal metastases in the mediastinum. The sensitivity, specificity, positive predictive value, and negative predictive value for 99mTc-sestamibi single-photon emission computed tomography/computed tomography in the hilum assessment were 31.6%, 95.5%, 85.7%, and 61.8%, respectively. The same values for the mediastinum were 14.3%, 97.1%, 50%, and 84.6%, respectively. For the hilar and mediastinal lymph nodes, chest tomography showed sensitivity values of 47.4% and 57.1%, specificity values of 95.5% and 91.2%, positive predictive values of 90% and 57.1% and negative predictive values of 67.7% and 91.2%, respectively. CONCLUSION: Single-photon emission computed tomography/computed tomography with 99mTc-sestamibi showed very low sensitivity and accuracy for the nodal staging of patients with non-small cell lung cancer, despite its high level of specificity. In addition, the performance of single-photon emission computed tomography/computed tomography added no relevant information compared to computed tomography that would justify its use in the routine preoperative staging of non-small cell lung carcinoma. PMID- 22086521 TI - Assessment of symptoms of urinary incontinence in women with polycystic ovary syndrome. AB - OBJECTIVES: The pelvic floor muscles are sensitive to androgens, and due to hyperandrogenism, women with polycystic ovary syndrome can have increased mass in these muscles compared to controls. The aim of this study is to compare reports of urine leakage and quality of life between women with and without polycystic ovary syndrome. METHODS: One hundred thirteen 18-to 40-year-old nulliparous women with polycystic ovary syndrome or without the disease (controls) were recruited at the University Hospital of School Medicine of Sao Paulo University at Ribeirao Preto City, Brazil. The subjects were not taking any hormonal medication, had not undergone previous pelvic surgery and did not exercise their pelvic floor muscles. The women were divided into the following four groups: I-polycystic ovary syndrome with normal body mass index (n = 18), II-polycystic ovary syndrome with body mass index >25 (n = 32), III-controls with normal body mass index (n = 29), and IV-controls with Body Mass Index >25 (n = 34). Quality of life was evaluated using the SF-36 questionnaire, and the subjects with urinary complaints also completed the International Consultation on Incontinence Questionnaire Short Form to evaluate the severity of their urinary incontinence. RESULTS: The replies to the International Consultation on Incontinence Questionnaire Short Form revealed a significant difference in urinary function between groups, with 24% of the subjects in group IV reporting urinary incontinence. The mean scores for the SF-36 questionnaire revealed that group II had the lowest quality of life. CONCLUSIONS: The control obese group (IV) reported a higher prevalence of urinary incontinence. There was no difference in the reported frequency of urine loss between the polycystic ovary syndrome and control groups with normal body mass index or between the polycystic ovary syndrome and control groups with body mass index >25. PMID- 22086522 TI - The validity and reliability of the Portuguese versions of three tools used to diagnose delirium in critically ill patients. AB - OBJECTIVES: The objectives of this study are to compare the sensitivity and specificity of three diagnostic tools for delirium (the Intensive Care Delirium Screening Checklist, the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet) in a mixed population of critically ill patients, and to validate the Brazilian Portuguese Confusion Assessment Method for Intensive Care Units. METHODS: The study was conducted in four intensive care units in Brazil. Patients were screened for delirium by a psychiatrist or neurologist using the Diagnostic and Statistical Manual of Mental Disorders. Patients were subsequently screened by an intensivist using Portuguese translations of the three tools. RESULTS: One hundred and nineteen patients were evaluated and 38.6% were diagnosed with delirium by the reference rater. The Confusion Assessment Method for Intensive Care Units had a sensitivity of 72.5% and a specificity of 96.2%; the Confusion Assessment Method for Intensive Care Units Flowsheet had a sensitivity of 72.5% and a specificity of 96.2%; the Intensive Care Delirium Screening Checklist had a sensitivity of 96.0% and a specificity of 72.4%. There was strong agreement between the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet (kappa coefficient = 0.96) CONCLUSION: All three instruments are effective diagnostic tools in critically ill intensive care unit patients. In addition, the Brazilian Portuguese version of the Confusion Assessment Method for Intensive Care Units is a valid and reliable instrument for the assessment of delirium among critically ill patients. PMID- 22086523 TI - Do omega-3 fatty acids prevent atrial fibrillation after open heart surgery? A meta-analysis of randomized controlled trials. AB - OBJECTIVES: N-3 polyunsaturated fatty acids have been proposed as a novel treatment for preventing postoperative atrial fibrillation due to their potential anti-inflammatory and anti-arrhythmic effects. However, randomized studies have yielded conflicting results. The objective of this study is to review randomized trials of N-3 polyunsaturated fatty acid use for postoperative atrial fibrillation. METHODS: Using the CENTRAL, PUBMED, EMBASE, and LILACS databases, a literature search was conducted to identify all of the studies in human subjects that reported the effects of N-3 polyunsaturated fatty acids on the prevention of postoperative atrial fibrillation in cardiac surgery patients. The final search was performed on January 30, 2011. There was no language restriction, and the search strategy only involved terms for N-3 polyunsaturated fatty acids (or fish oil), atrial fibrillation, and cardiac surgery. To be included, the studies had to be randomized (open or blinded), and the enrolled patients had to be >=18 years of age. RESULTS: Four randomized studies (three double-blind, one open label) that enrolled 538 patients were identified. The patients were predominantly male, the mean age was 62.3 years, and most of the patients exhibited a normal left atrial size and ejection fraction. N-3 polyunsaturated fatty acid use was not associated with a reduction in postoperative atrial fibrillation. Similar results were observed when the open-label study was excluded. CONCLUSIONS: There is insufficient evidence to suggest that treatment with N-3 polyunsaturated fatty acids reduces postoperative atrial fibrillation. Therefore, their routine use in patients undergoing cardiac surgery is not recommended. PMID- 22086524 TI - The ADA*2 allele of the adenosine deaminase gene (20q13.11) and recurrent spontaneous abortions: an age-dependent association. AB - OBJECTIVE: Adenosine deaminase acts on adenosine and deoxyadenosine metabolism and modulates the immune response. The adenosine deaminase G22A polymorphism (20q.11.33) influences the level of adenosine deaminase enzyme expression, which seems to play a key role in maintaining pregnancy. The adenosine deaminase 2 phenotype has been associated with a protective effect against recurrent spontaneous abortions in European Caucasian women. The aim of this study was to investigate whether the G22A polymorphism of the adenosine deaminase gene is associated with recurrent spontaneous abortions in Brazilian women. METHODS: A total of 311 women were recruited to form two groups: G1, with a history of recurrent spontaneous abortions (N = 129), and G2, without a history of abortions (N = 182). Genomic DNA was extracted from peripheral blood with a commercial kit and PCR-RFLP analysis was used to identify the G22A genetic polymorphism. Fisher's exact test and odds ratio values were used to compare the proportions of adenosine deaminase genotypes and alleles between women with and without a history of recurrent spontaneous abortion (p<0.05). The differences between mean values for categorical data were calculated using unpaired t tests. The Hardy Weinberg equilibrium was assessed with a chi-square test. RESULTS: Statistically significant differences were identified for the frequencies of adenosine deaminase genotypes and alleles between the G1 and G2 groups when adjusted for maternal age. CONCLUSIONS: The results suggest that the adenosine deaminase *2 allele is associated with a low risk for recurrent spontaneous abortions, but this association is dependent on older age. PMID- 22086525 TI - Revisiting stapled and handsewn loop ileostomy closures: a large retrospective series. AB - OBJECTIVE: To compare the surgical outcomes of stapled and handsewn closures in loop ileostomies. METHODS: The data of 225 patients requiring loop ileostomies from 2002 to 2007 were retrospectively evaluated. The patients underwent partial small-bowel resections and either handsewn or stapled anastomoses for the ileostomy closures. They were followed up postoperatively with routine surgical examinations. RESULTS: The study group consisted of 124 men and 101 women with a mean age of 49.12 years. The ileostomy closure was performed with handsewn in 129 patients and with stapled in 96 patients. The mean time to the first postoperative flatus was 2.426 days in the handsewn group and 2.052 days in the stapled group (p <0.05). The mean time to the first postoperative defecation was 3.202 days in the handsewn group and 2.667 days in the stapled group (p <0.05). The mean duration of patient hospital stay was 8.581 days for the handsewn group and 6.063 days for the stapled group (p <0.05). CONCLUSIONS: Patients who underwent ileostomy closure with stapled recovered faster in the postoperative period and required shorter hospital stays than those whose closures were performed with handsewn. In our opinion, stapled should be considered the gold standard for loop ileostomy closures. PMID- 22086526 TI - Development and analysis of a low-cost screening tool to identify and classify hearing loss in children: a proposal for developing countries. AB - OBJECTIVE: A lack of attention has been given to hearing health in primary care in developing countries. A strategy involving low-cost screening tools may fill the current gap in hearing health care provided to children. Therefore, it is necessary to establish and adopt lower-cost procedures that are accessible to underserved areas that lack other physical or human resources that would enable the identification of groups at risk for hearing loss. The aim of this study was to develop and analyze the efficacy of a low-cost screening tool to identify and classify hearing loss in children. METHODS: A total of 214 2-to-10 year-old children participated in this study. The study was conducted by providing a questionnaire to the parents and comparing the answers with the results of a complete audiological assessment. Receiver operating characteristic (ROC) curves were constructed, and discriminant analysis techniques were used to classify each child based on the total score. RESULTS: We found conductive hearing loss in 39.3% of children, sensorineural hearing loss in 7.4% and normal hearing in 53.3%. The discriminant analysis technique provided the following classification rule for the total score on the questionnaire: 0 to 4 points - normal hearing; 5 to 7 points - conductive hearing loss; over 7 points - sensorineural hearing loss. CONCLUSION: Our results suggest that the questionnaire could be used as a screening tool to classify children with normal hearing or hearing loss and according to the type of hearing loss based on the total questionnaire score. PMID- 22086527 TI - Mechanical evaluation of the resistance and elastance of post-burn scars after topical treatment with tretinoin. AB - OBJECTIVE: After burn injuries, scarred skin lacks elasticity, especially in hypertrophic scars. Topical treatment with tretinoin can improve the appearance and quality of the skin (i.e., texture, distensibility, color, and hydration). The objective of this prospective study was to examine the effects of treatment with 0.05% tretinoin for one year on the biomechanical behavior and histological changes undergone by facial skin with post-burn scarring. SETTING: Tertiary, Institutional. METHOD: Fifteen female patients who had suffered partial thickness burns with more than two years of evolution were selected. Skin biopsies were obtained initially and after one year of treatment. The resistance and elastance of these skin biopsies were measured using a mechanical oscillation analysis system. The density of collagen fibers, elastic fibers, and versican were determined using immunohistochemical analysis. RESULTS: Tretinoin treatment significantly lowered skin resistance and elastance, which is a result that indicates higher distensibility of the skin. However, tretinoin treatment did not significantly affect the density of collagen fibers, elastic fibers, or versican. CONCLUSION: Topical tretinoin treatment alters the mechanical behavior of post burn scarred skin by improving its distensibility and thus leads to improved quality of life for patients. PMID- 22086528 TI - Restless legs syndrome in subjects with a knee prosthesis: evidence that symptoms are generated in the periphery. AB - OBJECTIVE: There are no data adressing the prevalence of restless legs syndrome in subjects who have knee prosthesis. Therefore, we conducted a cross-sectional survey of subjects who underwent knee prosthesis surgery. METHOD: A total of 107 subjects (30 male, 77 female) were interviewed over the telephone regarding restless legs syndrome symptoms. If the patients exhibited symptoms of the syndrome, we conducted face-to-face interviews. Lastly, a therapeutic test with pramipexole was proposed for each subject. RESULTS: In our cohort, 7 males (23%) and 30 females (39%) had restless legs syndrome. Of these, 6 males and 23 females were submitted to face-to-face-interview. Of the males, 5 (83%) had restless legs after the knee surgery-exclusively in the operated leg- and reported no family restless legs history. One man had a prior case of bilateral restless legs syndrome, a positive family history and claimed exacerbation of symptoms in the operated leg. Among the females, 16 (69%) had restless legs prior to surgery. A total of 10 female patients reported bilateral symptoms, with fewer symptoms in the operated leg, while 6 displayed a worse outcome in the operated leg. The 7 females (31%) without restless legs prior to surgery and without a family history experienced symptoms only in the operated leg. All subjects responded favorably to the pramipexole therapeutic test. CONCLUSION: Our results suggest that secondary unilateral restless legs syndrome may ensue from knee prosthesis surgery and that the symptoms are generated in the peripheral nervous system. PMID- 22086529 TI - Vimentin and laminin are altered on cheek pouch microvessels of streptozotocin induced diabetic hamsters. AB - OBJECTIVE: Normal endothelial cells respond to shear stress by elongating and aligning in the direction of fluid flow. Hyperglycemia impairs this response and contributes to microvascular complications, which result in deleterious effects to the endothelium. This work aimed to evaluate cheek pouch microvessel morphological characteristics, reactivity, permeability, and expression of cytoskeleton and extracellular matrix components in hamsters after the induction of diabetes with streptozotocin. METHODS: Syrian golden hamsters (90-130 g) were injected with streptozotocin (50 mg/kg, i.p.) or vehicle either 6 (the diabetes mellitus 6 group) or 15 (the diabetes mellitus 15 group) days before the experiment. Vascular dimensions and density per area of vessels were determined by morphometric and stereological measurements. Changes in blood flow were measured in response to acetylcholine, and plasma extravasation was measured by the number of leakage sites. Actin, talin, alpha-smooth muscle actin, vimentin, type IV collagen, and laminin were detected by immunohistochemistry and assessed through a semiquantitative scoring system. RESULTS: There were no major alterations in the lumen, wall diameters, or densities of the examined vessels. Likewise, vascular reactivity and permeability were not altered by diabetes. The arterioles demonstrated increased immunoreactivity to vimentin and laminin in the diabetes mellitus 6 and diabetes mellitus 15 groups. DISCUSSION: Antibodies against laminin and vimentin inhibit branching morphogenesis in vitro. Therefore, laminin and vimentin participating in the structure of the focal adhesion may play a role in angiogenesis. CONCLUSIONS: Our results indicated the existence of changes related to cell-matrix interactions, which may contribute to the pathological remodeling that was already underway one week after induction of experimental diabetes. PMID- 22086530 TI - Impact of Plasma-Lyte pH 7.4 on acid-base status and hemodynamics in a model of controlled hemorrhagic shock. AB - OBJECTIVE: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance. METHODS: Controlled hemorrhagic shock (40% of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9% NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed. RESULTS: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions. CONCLUSION: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis. PMID- 22086531 TI - An overview of recently published medical papers in Brazilian scientific journals. AB - A brief review intended as information to the readership of Clinics on papers recently published under various medical headings in Brazilian scientific journals recently indexed or about to be indexed in ISI-THOMSON Journal Citation Reports. Journals covered in this review are Acta Ortopedica Brasileira, Arquivos Brasileiros de Cardiologia, Jornal Brasileiro de Pneumologia, Revista Brasileira de Cirurgia Cardiovascular and Revista da Associacao Medica Brasileira. PMID- 22086532 TI - Immunoglobulin G4-related systemic sclerosing disease in a patient with sclerosing cholangitis, inflammatory pseudotumors of the lung and multiple radiological patterns: a case report. PMID- 22086533 TI - The best approach for diagnosing primary sclerosing cholangitis. PMID- 22086534 TI - Primary Sjogren's syndrome in children: is a family approach indicated? PMID- 22086535 TI - Unusual presentation of multiple aneurysms of the ascending aorta. PMID- 22086537 TI - Aluminum-induced oxidative stress and changes in antioxidant defenses in the roots of rice varieties differing in Al tolerance. AB - The effects of aluminum (Al) on root elongation, lipid peroxidation, hydrogen peroxide (H(2)O(2)) accumulation, antioxidant levels, antioxidant enzymatic activity, and lignin content in the roots of the Al-tolerant rice variety azucena and the Al-sensitive variety IR64 were investigated. Treatment with Al induced a greater decrease in root elongation and a greater increase in H(2)O(2) and lipid peroxidation as determined by the total thiobarbituric acid-reactive substance (TBARS) level in IR64 than in azucena. Azucena had significantly higher levels of superoxide dismutase, ascorbate peroxidase, glutathione reductase, and glutathione peroxidase GSH POD activity compared with IR64. The concentrations of reduced glutathione (GSH) and ascorbic acid, and the GSH/GSSG ratio (reduced vs. oxidized glutathione) were also higher in azucena than in IR64 in the presence of Al. The addition of 1 mg/L GSH improved root elongation in both varieties and decreased H(2)O(2) production under Al stress. By contrast, treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis, decreased root elongation in azucena and stimulated H(2)O(2) production in both varieties. Moreover, Al treatment significantly increased the cytoplasmic activity of peroxidase (POD) as well as the levels of POD bound ionically and covalently to cell walls in the Al-sensitive variety. The lignin content was also increased. Treatment with exogenous H(2)O(2) also increased the lignin content and decreased root elongation in IR64. These results suggest that Al induces lignification in the roots of Al-sensitive rice varieties, probably through an increase in H(2)O(2) accumulation. PMID- 22086538 TI - Syrinx resolution after posterior fossa decompression in patients with scoliosis secondary to Chiari malformation type I. AB - INTRODUCTION: Description of syrinx resolution after posterior fossa decompression (PFD) in patients with scoliosis secondary to Chiari malformation type I (CMI) and syringomyelia (SM) has been rarely reported in the literature. This study was performed to investigate the outcome of PFD in patients with scoliosis secondary to CMI and to identify potential predictive factors for better outcome after PFD. MATERIAL AND METHODS: Patients with scoliosis secondary to CMI and SM, who had undergone PFD during the period 2000 through 2009, were recruited. Inclusion criteria were (1) age <= 18 years, (2) diagnosis of SM associated with CMI, (3) scoliosis as the first complaint, (4) having undergone preoperative and follow-up magnetic resonance imaging (MRI). Patients with acquired CMI anomalies or who had received syringosubarachnoid shunting were excluded. The maximal S/C ratio and syrinx length were measured to evaluate syrinx resolution after PFD. A 20% decrease in S/C ratio or length at the latest follow-up was defined as a significant radiographic improvement and complete resolution was used to describe the syrinx disappearing after PFD. RESULTS: 44 patients were recruited. Follow-up MRI was conducted for all 44 patients at 6 +/- 3 months postoperatively, for 37 patients at 2 years +/- 3 months, for 26 patients at 4 years +/- 3 months, and for 15 patients at 6 years +/- 3 months. 97.7% (43 of 44) of patients showed significant radiographic improvement by MRI. The distance of tonsillar descent (mm) was correlated significantly with the surgical outcome (r = 0.116, P = 0.013). Significant improvement was observed within 6 months postoperatively, with continued slow improvement after that. CONCLUSION: Syringes showed significant improvement after PFD in most patients with scoliosis secondary to CMI. Resolution generally occurred within 6 months follow-up and continued at a slow rate for several years. In addition, the severity of tonsillar descent is a potential predictor for better improvement after standard PFD. PMID- 22086539 TI - CT evaluation of upper thoracic spine for surgical application of transarticular screw placement. AB - INTRODUCTION: Although pedicle screw fixation has been increasingly used in the upper thoracic spine in recent years, controversies exist about the safety and complications such as nerve or vascular intrusion associated with the technique. In this study, an alternative method of transarticular screw fixation was validated. MATERIALS AND METHODS: Morphometric analysis was performed on computed tomography (CT) scans of the upper thoracic zygapophysial joints of C7, T1, T2 and T3 in 20 male and 20 female patients in the axial and sagittal planes. The degree of screw angulation was recorded in the sagittal and axial planes and the screw length was measured at the spinal level from C7 to T3. RESULTS: The smallest medial-lateral diameter and anterior-posterior diameter of IAP was found at T3 in the female patients and C7 in the male patients. The screw trajectory length ranged from 14.9 to 20.5 mm in all patients. All the above measurements were significantly different between male and female patients at all levels (P < 0.05). The mean value of screw trajectory angle was 19.3 degrees -20.1 degrees in the axial plane and 44.3 degrees -45.7 degrees in the sagittal plane. There was no statistically significant difference (P > 0.05) between male and female patients in the axial and sagittal angles. CONCLUSION: The morphometric data of C7-T3 zygapophysial joints indicate the suitable screw diameter and screw length for this technique. Transarticular screw fixation proved to be a potentially safe alternative to pedicle screw fixation in this region. PMID- 22086540 TI - Meter-long and robust supramolecular strands encapsulated in hydrogel jackets. PMID- 22086542 TI - Initialization independent clustering with actively self-training method. AB - The results of traditional clustering methods are usually unreliable as there is not any guidance from the data labels, while the class labels can be predicted more reliable by the semisupervised learning if the labels of partial data are given. In this paper, we propose an actively self-training clustering method, in which the samples are actively selected as training set to minimize an estimated Bayes error, and then explore semisupervised learning to perform clustering. Traditional graph-based semisupervised learning methods are not convenient to estimate the Bayes error; we develop a specific regularization framework on graph to perform semisupervised learning, in which the Bayes error can be effectively estimated. In addition, the proposed clustering algorithm can be readily applied in a semisupervised setting with partial class labels. Experimental results on toy data and real-world data sets demonstrate the effectiveness of the proposed clustering method on the unsupervised and the semisupervised setting. It is worthy noting that the proposed clustering method is free of initialization, while traditional clustering methods are usually dependent on initialization. PMID- 22086543 TI - A smart health monitoring chair for nonintrusive measurement of biological signals. AB - We developed nonintrusive methods for simultaneous electrocardiogram, photoplethysmogram, and ballistocardiogram measurements that do not require direct contact between instruments and bare skin. These methods were applied to the design of a diagnostic chair for unconstrained heart rate and blood pressure monitoring purposes. Our methods were operationalized through capacitively coupled electrodes installed in the chair back that include high-input impedance amplifiers, and conductive textiles installed in the seat for capacitive driven right-leg circuit configuration that is capable of recording electrocardiogram information through clothing. Photoplethysmograms were measured through clothing using seat mounted sensors with specially designed amplifier circuits that vary in light intensity according to clothing type. Ballistocardiograms were recorded using a film type transducer material, polyvinylidenefluoride (PVDF), which was installed beneath the seat cover. By simultaneously measuring signals, beat-to beat heart rates could be monitored even when electrocardiograms were not recorded due to movement artifacts. Beat-to-beat blood pressure was also monitored using unconstrained measurements of pulse arrival time and other physiological parameters, and our experimental results indicated that the estimated blood pressure tended to coincide with actual blood pressure measurements. This study demonstrates the feasibility of our method and device for biological signal monitoring through clothing for unconstrained long-term daily health monitoring that does not require user awareness and is not limited by physical activity. PMID- 22086544 TI - Designer peptide surfactants stabilize diverse functional membrane proteins. AB - Multi-spanning integral membrane proteins, including G-protein coupled receptors (GPCR), ion channels, and ion transporters, comprise a major class of drug targets. However, despite their vital importance, most molecular structures of membrane proteins remain elusive. This is largely due to lack of effective materials and methods to stabilize their functional conformation for sufficient time. Thus finding optimal surfactants and developing new approaches to study fundamental properties of unstable membrane proteins is urgently needed. In this tutorial review we summarize designer peptides with surfactant properties and their usefulness to stabilize membrane proteins. These peptide surfactants present new opportunities for the stabilization and characterization of diverse membrane proteins. Previous studies on the interaction between surfactant peptides and membrane proteins revealed strategies to design new peptides tailor made for the stabilization of specific proteins. We review examples of solubilization, purification, long-term stabilization of membrane proteins, and the design principles of peptide sequences. We discuss future trends for exploiting spatial features, thermodynamic parameters, and self-assembling properties to create peptide surfactant structures to facilitate the characterization of diverse membrane proteins. PMID- 22086546 TI - Biomechanical investigation of the stabilization principle of the Latarjet procedure. AB - PURPOSE: The purpose of the study was to determine the biomechanical status of the different components of the Latarjet procedure. The anterior capsule reconstruction with the transferred coracoacromial ligament (CAL) and the necessity of an intact subscapularis tendon were of particular interest. We hypothesized that the anterior capsule reconstruction will have a significant effect and that the Latarjet procedure will lose its stabilizing effect if the subscapularis tendon is torn. METHODS: Stability testing of 12 human shoulder specimens was performed. After testing of the intact joint, a combined anterior glenoid and capsule defect was set arthroscopically. Then the Latarjet procedure was performed using an open approach and tested with and without loading of the conjoint tendons (10 N). Afterwards, the specimens were distributed into two groups and the Latarjet technique was reduced stepwise: dissection of the CAL, dissection of the conjoint tendons (group A); reduction of the coracoid segment, dissection of the subscapularis tendon (group B). Biomechanical testing was performed for each condition in two positions: 60 degrees of glenohumeral abduction with neutral rotation and with 60 degrees of external rotation; each with a passive humerus load of 30 N in the anterior, inferior and anteroinferior direction. RESULTS: The Latarjet technique with load applied to the conjoint tendons significantly reduced translation compared with the defect condition for all tested positions in all directions. In group A, the CAL-dissection led to a significant increase of anterior translation (+5.0 mm, p = 0.003) and inferior translation (+7.3 mm, p = 0.025) in neutral rotation and of anterior translation in 60 degrees of external rotation (+4.4 mm, p = 0.034). In group B, the reduction of the coracoid bone down to the coracoid tip resulted in a significant increase of only the anterior translation in abduction and 60 degrees of external rotation (+4.5 mm, p = 0.05). In contrast, the detachment of the subscapularis tendon led to a significant increase of translation in all testing positions except the inferior direction in the neutral rotation. CONCLUSIONS: We found the anterior capsule reconstruction to represent a significant contribution to the stabilizing effect of the Latarjet procedure, whereas a deficiency of the subscapularis tendon eliminates its effect. CLINICAL RELEVANCE: We recommend to perform the Latarjet technique with an anterior capsule reconstruction (e.g. CAL transfer) and with a transfer of the coracoid bone block rather than a transposition of the coracoid tip. Furthermore, we were able to show that an intact subscapularis tendon is a necessary prerequisite for a reliable stabilization. PMID- 22086547 TI - Unexpected injury of the orthopaedic surgeon: a case report of a hammer splinter. AB - Sharps injuries have become one of the most important occupational injuries and they are common during surgery, with rates between 1.7 and 6.9% of all surgical procedures. This case report, however, revealed an extremely rare and unexpected condition, which could not be prevented by the reasonable safety precautions against injury. Closed reduction and closed intramedullary fixation was planned for the patient with humeral shaft fracture. While advancing the nail by hammering a piece of metal detached. A short time following the commencement of the procedure, the surgeon who was performing the operation felt a sudden severe pain in the neck. A radio-opaque intensity in the cervical region was detected on X-rays. There was a piece of metal from the hammer. The risk encountered in the present case comprises a condition, the prevention of which is probably impossible with the frequently utilized preventive measures against injuries. For this reason, the operating room team and in particular, the surgeon, should be careful about possible expected injuries, as well as the unexpected ones. Sharps injuries continue to be a serious concern for all healthcare workers. In some studies however, reporting of sharps injuries by healthcare workers remains a problem with reporting levels cited as low as 15% and as high as 90% (Kerr H-L, Stewart N Ann R Coll Surg Engl 91:430-432, [6]). Guo et al. pointed out the most recent sharps injuries at work, and syringe needles was by far the most important items causing injuries, followed by glass products, suture needles, and intravenous catheters. PMID- 22086545 TI - Visual object categorization in birds and primates: integrating behavioral, neurobiological, and computational evidence within a "general process" framework. AB - Previous comparative work has suggested that the mechanisms of object categorization differ importantly for birds and primates. However, behavioral and neurobiological differences do not preclude the possibility that at least some of those mechanisms are shared across these evolutionarily distant groups. The present study integrates behavioral, neurobiological, and computational evidence concerning the "general processes" that are involved in object recognition in vertebrates. We start by reviewing work implicating error-driven learning in object categorization by birds and primates, and also consider neurobiological evidence suggesting that the basal ganglia might implement this process. We then turn to work with a computational model showing that principles of visual processing discovered in the primate brain can account for key behavioral findings in object recognition by pigeons, including cases in which pigeons' behavior differs from that of people. These results provide a proof of concept that the basic principles of visual shape processing are similar across distantly related vertebrate species, thereby offering important insights into the evolution of visual cognition. PMID- 22086548 TI - More effective antimicrobial mastoparan derivatives, generated by 3D-QSAR-Almond and computational mutagenesis. AB - Antimicrobial peptides are drugs used against a wide range of pathogens which present a great advantage: in contrast with antibiotics they do not develop resistance. The wide spectrum of antimicrobial peptides advertises them in the research and pharmaceutical industry as attractive starting points for obtaining new, more effective analogs. Here we predict the antimicrobial activity against Bacillus subtilis (expressed as minimal inhibitory concentration values) for 33 mastoparan analogs and their new derivatives by a non-aligned 3D-QSAR (quantitative structure-activity relationship) method. We establish the contribution to antimicrobial activity of molecular descriptors (hydrophobicity, hydrogen bond donor and steric), correlated with contributions from the membrane environment (sodium, potassium, chloride). Our best QSAR models show significant cross-validated correlation q(2) (0.55-0.75), fitted correlation r(2) (greater than 0.90) coefficients and standard error of prediction SDEP (less than 0.250). Moreover, based on our most accurate 3D-QSAR models, we propose nine new mastoparan analogs, obtained by computational mutagenesis, some of them predicted to have significantly improved antimicrobial activity compared to the parent compound. PMID- 22086549 TI - Catalyzing denitrification of Paracoccus versutus by immobilized 1,5 dichloroanthraquinone. AB - The accelerating effect of non-dissolved redox mediator (1,5 dichloroanthraquinone) on the biological denitrification was investigated in this paper using 1,5-dichloroanthraquinone immobilized by calcium alginate (CA) and a heterotrophic denitrification bacterium of Paracoccus versutus (GU111570). The results suggested that the denitrification rate was enhanced 2.1 fold by 25 mmol l(-1) 1,5-dichloroanthraquinone of this study, and a positive correlation was found for the denitrification rate and 1,5-dichloroanthraquinone concentrations from 0 to 25 mmol l(-1). According to the change characteristic of NO(3) (-) and NO(2) (-) during the denitrification process, the tentative accelerating mechanism of the denitrification by redox mediators was put forward, and redox mediator might play the role of reduced cofactors like NADH, N(A)DH and SDH, or the similar ubiquinol/ubiquinone (Q/QH(2)) role during the denitrification process. PMID- 22086550 TI - Effect of erythropoiesis-stimulating agents in acute ST-segment elevation myocardial infarction: a systematic review. AB - PURPOSE: Current evidence suggests that erythropoiesis-stimulating agents (ESAs), including erythropoietin and darbepoetin, may have a direct cardio-protective effect. However, randomized controlled trials (RCTs) assessing the efficacy and safety of ESAs in patients with acute ST-segment elevation myocardial infarction (STEMI) have yielded heterogeneous results. Here, we performed a meta-analysis of RCTs to assess whether the administration of ESAs can improve cardiac functional parameters, such as left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV), and attenuate infarct size in patients with acute STEMI. METHODS AND RESULTS: The PubMed, EBSCO, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for relevant RCT studies on ESAs published before May 13, 2011. A total of nine RCTs involving 1,244 participants were identified. The original data of these studies were aggregated using fixed effect models. Compared with controls, the administration of ESAs showed a slight but significant improvement in LVEF (1.38%; 95% confidence interval 0.38-2.37%; p = 0.007). However, no significant improvement in LVEDV, LVESV, and infarct size was observed, and no increase in all-cause severe adverse effect was indicated. CONCLUSIONS: Our meta-analysis indicates that the superiority of ESAs over conventional therapy in patients with acute STEMI is limited using current procedures. However, there is evidence to suggest that the timing and dosing of ESA administration may be optimized. Moreover, the long-term cardio-protective effect of ESAs in this patient population may be beneficial and worth exploring. PMID- 22086551 TI - Effects of cage mesh on pointing: hand shapes in chimpanzees (Pan troglodytes). AB - It has been speculated that cage mesh exerts a shaping influence on reaching behavior by captive apes, which is then misconstrued as pointing by human observers. Although this notion is clearly falsified by the pointing of captive language-trained apes-who point in the absence of intervening cage mesh nevertheless, the degree to which cage mesh might influence pointing hand shapes by captive great apes in other housing environments remains relatively unexplored. We examined 259 pointing gestures displayed in archival footage from over 18 h of observation by three nonlanguage-trained chimpanzees housed at a biomedical research center. We coded points in relation to how close to the boundaries of the diamond-shaped cage mesh their points were displayed. We found that points with the whole hand were significantly more likely to be displayed away from the mesh boundaries, relative to points with the index finger or other single-digit points. However, points of each hand shape were displayed at each location, demonstrating that these physical parameters do not fully account for the number of fingers extended while pointing by chimpanzees. PMID- 22086552 TI - Durable remission with salvage second autotransplants in patients with multiple myeloma. AB - BACKGROUND: High-dose chemotherapy with autologous hematopoietic cell transplant (auto-HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto-HCT for relapsed patients, particularly in the era of novel therapeutics, is not well defined. METHODS: The authors performed a retrospective analysis of all 44 myeloma patients (24 men, 20 women) who received a second auto-HCT as salvage between January 3, 1992 and November 4, 2008 at The University of Texas MD Anderson Cancer Center. RESULTS: Median interval between the first and salvage auto-HCT was 30 months (range, 2-78 months). Median age at salvage HCT was 54 years (range, 38-73 years), and median number of salvage treatment regimens was 2 (range, 0-5). Eleven (25%) patients had high-risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto-HCT. Ten patients (23%) experienced grade 3 or higher nonhematologic toxicity after the salvage auto-HCT. One patient died within 100 days, for a treatment-related mortality of 2%. Best responses after salvage chemotherapy + salvage auto-HCT were as follows: complete response (CR) + near CR, 11%; partial response, 79%; overall response rate, 90%. Eighteen (41%) patients received post auto-HCT maintenance therapy. Median follow-up from salvage HCT was 41 months. Kaplan-Meier estimates of median progression-free survival (PFS) and overall survival (OS) from time of salvage auto-HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression after first auto-HCT, greater number of prior therapies, African American race, and immunoglobulin G subtype were significantly associated with worse OS. CONCLUSIONS: In selected myeloma patients, a second auto-HCT for salvage therapy is well tolerated, with acceptable toxicity. The overall response rate and PFS are comparable to other salvage regimens. PMID- 22086553 TI - P2X receptor antagonists for pain management: examination of binding and physicochemical properties. AB - Enhanced sensitivity to noxious stimuli and the perception of non-noxious stimuli as painful are hallmark sensory perturbations associated with chronic pain. It is now appreciated that ATP, through its actions as an excitatory neurotransmitter, plays a prominent role in the initiation and maintenance of chronic pain states. Mechanistically, the ability of ATP to drive nociceptive sensitivity is mediated through direct interactions at neuronal P2X3 and P2X2/3 receptors. Extracellular ATP also activates P2X4, P2X7, and several P2Y receptors on glial cells within the spinal cord, which leads to a heightened state of neural-glial cell interaction in ongoing pain states. Following the molecular identification of the P2 receptor superfamilies, selective small molecule antagonists for several P2 receptor subtypes were identified, which have been useful for investigating the role of specific P2X receptors in preclinical chronic pain models. More recently, several P2X receptor antagonists have advanced into clinical trials for inflammation and pain. The development of orally bioavailable blockers for ion channels, including the P2X receptors, has been traditionally difficult due to the necessity of combining requirements for target potency and selectivity with suitable absorption distribution, metabolism, and elimination properties. Recent studies on the physicochemical properties of marketed orally bioavailable drugs, have identified several parameters that appear critical for increasing the probability of achieving suitable bioavailability, central nervous system exposure, and acceptable safety necessary for clinical efficacy. This review provides an overview of the antinociceptive pharmacology of P2X receptor antagonists and the chemical diversity and drug-like properties for emerging antagonists of P2X3, P2X2/3, P2X4, and P2X7 receptors. PMID- 22086555 TI - Inhibition of beta-amyloid peptide aggregation by multifunctional carbazole-based fluorophores. PMID- 22086554 TI - Using antibodies against P2Y and P2X receptors in purinergic signaling research. AB - The broad expression pattern of the G protein-coupled P2Y receptors has demonstrated that these receptors are fundamental determinants in many physiological responses, including neuromodulation, vasodilation, inflammation, and cell migration. P2Y receptors couple either G(q) or G(i) upon activation, thereby activating different signaling pathways. Ionotropic ATP (P2X) receptors bind extracellular nucleotides, a signal which is transduced within the P2X protein complex into a cation channel opening, which usually leads to intracellular calcium concentration elevation. As such, this family of proteins initiates or shapes several cellular processes including synaptic transmission, gene expression, proliferation, migration, and apoptosis. The ever-growing range of applications for antibodies in the last 30 years attests to their major role in medicine and biological research. Antibodies have been used as therapeutic tools in cancer and inflammatory diseases, as diagnostic reagents (flow cytometry, ELISA, and immunohistochemistry, to name a few applications), and in widespread use in biological research, including Western blot, immunoprecipitation, and ELISPOT. In this article, we will showcase several of the advances that scientists around the world have achieved using the line of antibodies developed at Alomone Labs for P2Y and P2X receptors. PMID- 22086556 TI - Starting a new life: sperm PLC-zeta mobilizes the Ca2+ signal that induces egg activation and embryo development: an essential phospholipase C with implications for male infertility. AB - We have discovered that a single sperm protein, phospholipase C-zeta (PLCzeta), can stimulate intracellular Ca(2+) signalling in the unfertilized oocyte ('egg') culminating in the initiation of embryonic development. Upon fertilization by a spermatozoon, the earliest observed signalling event in the dormant egg is a large, transient increase in free Ca(2+) concentration. The fertilized egg responds to the intracellular Ca(2+) rise by completing meiosis. In mammalian eggs, the Ca(2+) signal is delivered as a train of long-lasting cytoplasmic Ca(2+) oscillations that begin soon after gamete fusion and persist beyond the completion of meiosis. Sperm PLCzeta effects Ca(2+) release from egg intracellular stores by hydrolyzing the membrane lipid PIP(2) and consequent stimulation of the inositol 1,4,5-trisphosphate (InsP(3) ) receptor Ca(2+) signalling pathway, leading to egg activation and early embryogenesis. Recent advances have refined our understanding of how PLCzeta induces Ca(2+) oscillations in the egg and also suggest its potential dysfunction as a cause of male infertility. PMID- 22086558 TI - Genetic variants of a BH3-only pro-apoptotic gene, PUMA, and risk of HPV16 associated squamous cell carcinoma of the head and neck. AB - P53 up-regulated modulator of apoptosis (PUMA) is a critical factor in the intrinsic apoptotic pathway. Through PUMA-dependent mechanisms, human papillomavirus 16 (HPV16) oncoprotein may affect apoptosis by E6-mediated p53 degradation. To examine whether the PUMA variants modify the association between HPV16 serology and risk of squamous cell carcinoma of the head and neck (SCCHN), we genotyped two polymorphisms in the PUMA promoter (rs3810294 and rs2032809) in 380 cases and 335 cancer-free controls of non-Hispanic Whites, who were frequency matched by age (+/-5 yr), sex, smoking, and drinking status. We found that each individual polymorphism had only a modest impact on risk of SCCHN, particularly in oropharyngeal cancer for rs3810294 and non-oropharyngeal cancer for rs2032809. After we stratified the individuals by HPV16 serology, and used those with the corresponding common homozygous genotype and HPV16 seronegativity as the reference group, for each polymorphism we found that the risk of SCCHN associated with HPV16 seropositivity was higher among those with variant genotypes than those with the corresponding common homozygous genotype. Notably, this effect modification was particularly pronounced in several subgroups including never smokers, never drinkers, younger patients, and patients with oropharyngeal cancer. Furthermore, we also characterized the functional relevance of the two polymorphisms to explore the genotype-phenotype correlation. Our results suggested that the PUMA promoter polymorphisms may be a biomarker for risk of HPV16-associated SCCHN, particularly in never smokers, never drinkers, younger patients, and patients with oropharyngeal cancer. Larger studies are needed to validate our findings. PMID- 22086560 TI - Quantitative assessment of tumour associated neovascularisation in patients with liver cirrhosis and hepatocellular carcinoma: role of dynamic-CT perfusion imaging. AB - OBJECTIVE: To determine the value of perfusion computed tomography (CT-p) in the quantitative assessment of tumour-related neoangiogenesis processes in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-two biopsy proven HCC lesions were examined with dynamic CT investigations during injection of 50 mL of contrast agent (350 mgI/mL). A dedicated perfusion software which generated a quantitative map of arterial and portal perfusion by means of a colour scale was employed. The following parameters related to the blood microcirculation and tissue perfusion were calculated: hepatic perfusion (Perf), tissue blood volume (BV), hepatic perfusion index (HPI), arterial perfusion (AP), portal perfusion (PP), and time to peak (TTP). Perfusion parameters were statistically analysed, comparing neoplastic lesions with cirrhotic parenchyma. RESULTS: Perf, BV, HPI and AP values were higher (P < 0.001), whereas PP and TTP were lower (P < 0.001) in HCC relative to the surrounding liver. No significant correlation was found between perfusion parameters and HCC grade. Values of perfusion parameters in the cirrhotic liver of patients with and without HCC were not significantly different. CONCLUSIONS: Our results suggest that CT-p can help in non-invasive quantification of tumour blood supply, related to the formation of new arterial structures (neoangiogenesis), which are essential for tumour growth. KEY POINTS: Perfusion computed tomography (CT) enables depiction of tumour vascular physiology. Perfusion CT is non-invasive and is now quick to perform and analyse. Quantitative measurements of hepatic perfusion provide important information about hepatocellular carcinoma (HCC). Such perfusion CT data may help in the determination of the outcome of HCC. Perfusion CT can act as an in-vivo biomarker of tumour-related angiogenesis. PMID- 22086561 TI - Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival. AB - PURPOSE: To establish the potential for tumour heterogeneity in non-small cell lung cancer (NSCLC) as assessed by CT texture analysis (CTTA) to provide an independent marker of survival for patients with NSCLC. MATERIALS AND METHODS: Tumour heterogeneity was assessed by CTTA of unenhanced images of primary pulmonary lesions from 54 patients undergoing (18)F-fluorodeoxyglucose (FDG) PET CT for staging of NSCLC. CTTA comprised image filtration to extract fine, medium and coarse features with quantification of the distribution of pixel values (uniformity) within the filtered images. Receiver operating characteristics identified thresholds for PET and CTTA parameters that were related to patient survival using Kaplan-Meier analysis. RESULTS: The median (range) survival was 29.5 (1-38) months. 24, 10, 14 and 6 patients had tumour stages I, II, III and IV respectively. PET stage and tumour heterogeneity assessed by CTTA were significant independent predictors of survival (PET stage: Odds ratio 3.85, 95% confidence limits 0.9-8.09, P = 0.002; CTTA: Odds ratio 56.4, 95% confidence limits 4.79-666, p = 0.001). SUV was not a significantly associated with survival. CONCLUSION: Assessment of tumour heterogeneity by CTTA of non-contrast enhanced images has the potential for to provide a novel, independent predictor of survival for patients with NSCLC. KEY POINTS: Computed tomography is a routine staging procedure in non-small cell lung cancer. CT texture analysis (CTTA) can quantify heterogeneity within these lung tumours. CTTA seems to offer a novel independent predictor of survival for NSCLC. CTTA could contribute to disease risk-stratification for patients with NSCLC. PMID- 22086562 TI - Diagnosis by treatment. PMID- 22086563 TI - Maximum saccharification of cellulose complex by an enzyme cocktail supplemented with cellulase from newly isolated Aspergillus fumigatus ECU0811. AB - Either the natural biodegradation process or the industrial hydrolytic process requires synergistic interactions between various cellulases. However, it is sometimes impeded by low hydrolytic rate of existing cellulases and the lack of accessory enzymes. Herein, the ability of a commercial cellulase (Spezyme CP, from Genencor) to degrade steam explosion-pretreated corn stover was significantly improved. Firstly, a fungal cellulase producer, Aspergillus fumigatus ECU0811, was isolated from hundreds of soil samples. A 96-deep-well microscale-based platform was developed here to reduce the labor-intensive screening work and proved to be consistent with macroscale screening work. After optimization of fermentation, 3% corn cob could induce A. fumigatus ECU0811 to yield the highest cellulase production. Based on the high activities of beta glucosidase and xylanase by A. fumigatus ECU0811, 0.91 and 125 U/mg protein, respectively, an enzyme cocktail was composed with a fixed dosage of Spezyme CP (CPCel) at 14.2 filter paper units (FPU)/g glucan and varied dosages of A. fumigatus cellulase (AFCel). Consequently, the glucan-to-glucose conversion of corn stover was increased from 25.6% in the presence of CPCel at a dosage of 14.2 FPU/g glucan to 99.5% in the presence of the enzyme cocktail (14.2 FPU CPCel plus 1.21 FPU AFCel per gram of glucan). On the other side, it reduced the total protein amount of CPCel by as much as tenfold, which extremely improved the hydrolytic rate of Spezyme CP and reduced its dosage. PMID- 22086564 TI - Characterization of a thermostable family 1 Glycosyl Hydrolase enzyme from Putranjiva roxburghii seeds. AB - A 66-kDa thermostable family 1 Glycosyl Hydrolase (GH1) enzyme with beta glucosidase and beta-galactosidase activities was purified to homogeneity from the seeds of Putranjiva roxburghii belonging to Euphorbiaceae family. N-terminal and partial internal amino acid sequences showed significant resemblance to plant GH1 enzymes. Kinetic studies showed that enzyme hydrolyzed p-nitrophenyl beta-D: glucopyranoside (pNP-Glc) with higher efficiency (K (cat)/K (m) = 2.27 x 10(4) M(-1) s(-1)) as compared to p-nitrophenyl beta-D: -galactopyranoside (pNP-Gal; K (cat)/K (m) = 1.15 x 10(4) M(-1) s(-1)). The optimum pH for beta-galactosidase activity was 4.8 and 4.4 in citrate phosphate and acetate buffers respectively, while for beta-glucosidase it was 4.6 in both buffers. The activation energy was found to be 10.6 kcal/mol in the temperature range 30-65 degrees C. The enzyme showed maximum activity at 65 degrees C with half life of ~40 min and first order rate constant of 0.0172 min(-1). Far-UV CD spectra of enzyme exhibited alpha, beta pattern at room temperature at pH 8.0. This thermostable enzyme with dual specificity and higher catalytic efficiency can be utilized for different commercial applications. PMID- 22086565 TI - Enhanced beta-galactosidase production from whey powder by a mutant of the psychrotolerant yeast Guehomyces pullulans 17-1 for hydrolysis of lactose. AB - In order to isolate beta-galactosidase overproducers of the psychrotolerant yeast Guehomyces pullulans 17-1, its cells were mutated by using nitrosoguanidine (NTG). One mutant (NTG-133) with enhanced beta-galactosidase production was obtained. The mutant grown in the production medium with 30.0 g/l lactose and 2.0 g/l glucose could produce more beta-galactosidase than the same mutant grown in the production medium with only 30.0 g/l lactose while beta-galactosidase production by its wild type was sensitive to the presence of glucose in the medium. It was found that 40.0 g/l of the whey powder was the most suitable for beta-galactosidase production by the mutant. After optimization of the medium and cultivation conditions, the mutant could produce 29.2 U/ml of total beta galactosidase activity within 132 h at the flask level while the mutant could produce 48.1 U/ml of total beta-galactosidase activity within 144 h in 2-l fermentor. Over 77.1% of lactose in the whey powder (5.0% w/v) was hydrolyzed in the presence of the beta-galactosidase activity of 280 U/g of lactose within 9 h while over 77.0% of lactose in the whey was hydrolyzed in the presence of beta galactosidase activity of 280 U/g of lactose within 6 h. This was the first time to show that the beta-galactosidase produced by the psychrotolerant yeast could be used for hydrolysis of lactose in the whey powder and whey. PMID- 22086566 TI - Occupational exposure to benzene and chromosomal structural aberrations in the sperm of Chinese men. AB - BACKGROUND: Benzene is an industrial chemical that causes blood disorders, including acute myeloid leukemia. We previously reported that occupational exposures near the U.S. Occupational Safety and Health Administration permissible exposure limit (8 hr) of 1 ppm was associated with sperm aneuploidy. OBJECTIVE: We investigated whether occupational exposures near 1 ppm increase the incidence of sperm carrying structural chromosomal aberrations. METHODS: We applied a sperm fluorescence in situ hybridization assay to measure frequencies of sperm carrying partial chromosomal duplications or deletions of 1cen or 1p36.3 or breaks within 1cen-1q12 among 30 benzene-exposed and 11 unexposed workers in Tianjin, China, as part of the China Benzene and Sperm Study (C-BASS). Exposed workers were categorized into low-, moderate-, and high-exposure groups based on urinary benzene (medians: 2.9, 11.0, and 110.6 ug/L, respectively). Median air benzene concentrations in the three exposure groups were 1.2, 3.7, and 8.4 ppm, respectively. RESULTS: Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for all structural aberrations combined were 1.42 (95% CI: 1.10, 1.83), 1.44 (95% CI: 1.12, 1.85), and 1.75 (95% CI: 1.36, 2.24) and for deletion of 1p36.3 alone were 4.31 (95% CI: 1.18, 15.78), 6.02 (95% CI: 1.69, 21.39), and 7.88 (95% CI: 2.21, 28.05) for men with low, moderate, and high exposure, respectively, compared with unexposed men. Chromosome breaks were significantly increased in the high-exposure group [IRR 1.49 (95% CI: 1.10, 2.02)]. CONCLUSIONS: Occupational exposures to benzene were associated with increased incidence of chromosomally defective sperm, raising concerns for worker infertility and spontaneous abortions as well as mental retardation and inherited defects in their children. Our sperm findings point to benzene as a possible risk factor for de novo 1p36 deletion syndrome. Because chromosomal aberrations in sperm can arise from defective stem cells/spermatogonia, our findings raise concerns that occupational exposure to benzene may have persistent reproductive effects in formerly exposed workers. PMID- 22086567 TI - Hidden renal dysfunction causes increased in-hospital mortality risk after coronary artery bypass graft surgery. AB - INTRODUCTION AND OBJECTIVES: Preoperative chronic renal dysfunction is an independent predictor of mortality in cardiac surgery. As normal range serum creatinine is not representative of normal renal function, we compared mortality rates, total hospital stay and post-surgical hospital stay for patients who underwent isolated coronary artery bypass surgery with serum creatinine < 1.5mg/dL as to their estimated creatinine clearance, normal or impaired. METHODS: In 4,765 patients submitted to coronary artery bypass surgery between January/1996 and June/2004, the creatinine clearance was estimated by the Cockroft-Gault equation. Impaired renal function was considered as a creatinine clearance <60 mL/min/1.73 m2 (chronic renal disease stage 3 - National Kidney Foundation-USA). In hospital mortality, total hospital stay, and post-surgical hospital stay were compared. RESULTS: 4,688 patients had the required data, and 4,403 presented serum creatinine < 1.5 mg/dL - 3,177 with creatinine clearance > 60 mL/min (Group A), and 1,226 with <60 mL/min (Group B). Group B patients had significantly higher total hospital stay and post-surgical hospital stay than those in Group A (respectively 2.85 and 1.79 more days--P < 0.0001). Relative risk of in-hospital death was 2.09 to Group B (95%CI:1.54-2.84) when compared to Group A. CONCLUSIONS: More than one quarter of the patients with serum creatinine <1.5 mg/dL had creatinine clearance <60 mL/min. This expressive number of patients, that would not have their renal dysfunction detected by the serum creatinine parameter alone, had double the risk of death, longer total hospital stay and post-surgical hospital stay than the other patients with serum creatinine < 1.5mg/dL. PMID- 22086568 TI - Outcomes of patients subjected to aortic valve replacement surgery using mechanical or biological prostheses. AB - OBJECTIVE: This paper evaluates outcomes in patients subjected to surgery for replacement of the aortic valve using biological or mechanical substitutes, where selection of the type of prosthesis is relevant. METHODS: Three hundred and one patients, randomly selected, who had been subjected to aortic valve replacement surgery between 1990 and 2005, with a maximum follow-up period of 20 years. RESULTS: Survival at 5, 10 and 15 years after surgery using mechanical substitute was 83.9%, 75.4% and 60.2% and, for biological substitute, was 89.3%, 70.4% and 58.4%, respectively (P = 0.939). Factors associated with death were: age, obesity, pulmonary disease, arrhythmia, bleeding and aortic valve failure. Probability free of reoperation for these patients at 5, 10 and 15 years after surgery using mechanical substitute was 97.9%, 95.8% and 95.8% and, for those using bioprostheses, was 94.6%, 91.0% and 83.3%, respectively (P = 0.057). Factors associated with reoperation were: renal failure, prosthesis endocarditis and age. Probability free of bleeding events at 5, 10 and 15 years after surgery using mechanical substitute was 94.5%, 91.7% and 91.7% and, for bioprostheses, was 98.6%, 97.8% and 97.8%, respectively (P = 0.047). Factors associated with bleeding events were: renal failure and mechanical prostheses. CONCLUSIONS: The authors have concluded that: 1) mortality was statistically similar in the groups; 2) patient characteristics at baseline were a major determinant of late mortality after surgery; 3) there was a tendency toward reoperation in the bioprostheses group; 4) patients using mechanical prosthesis had more bleeding events as time passed; 5) data presented in this paper is in accordance with current literature. PMID- 22086569 TI - Transcatheter aortic valve implantation: results of the current development and implantation of a new Brazilian prosthesis. AB - OBJECTIVE: Aortic valve replacement is a routine procedure with acceptable risk, but in some cases, such risk can justify contraindication. Minimally invasive transcatheter aortic valve implantation has emerged as an alternative, with lower morbidity and mortality. The aim of this study was clinical, safety and efficacy assessment. METHODS: Thirty-three high risk patients underwent transcatheter balloon expandable aortic valve implantation. Mean Logistic EuroScore risk was 39.30% and STS score 30.28%. Eight patients presented with dysfunctional bioprosthesis, remaining ones presented calcified aortic stenosis. Procedures were performed in a hybrid OR under fluoroscopic and echocardiography guidance. Using a left minithoracotomy the prosthesis were implanted trough the ventricular apex under rapid ventricular pacing or hemorrhagic shock. Echocardiographic and angiographic controls were performed. RESULTS: Implant was feasible in 30 cases. Three conversions occured. There was only one case of operative death. Median transvalvular aortic gradient reduced from 43.58 mmHg to 10.54 mmHg. Left ventricular function improved in the first 7 postoperative days. Paravalvular aortic regurgitation was mild and present in 30.30%. One case presented major vascular complication and another one permanent pacemaker implant. One major stroke case occurred. Overall 30-day mortality was 18.18%. CONCLUSION: The transapical implantation of catheter mounted bioprosthesis is a safe procedure with acceptable midterm results. Long term follow-up with increased sample power is mandatory in order to access hemodynamic, life quality and survival. PMID- 22086570 TI - Transcatheter implantation of self-expandable valved prosthesis in outlet right ventricle an experimental study in pigs. AB - INTRODUCTION: Patients with congenital heart disease who underwent pulmonary valvotomy or surgery to open the pulmonary valve ring are prone to develop residual pulmonary insufficiency or stenosis that may lead to right heart failure with clinical deterioration. These children require multiple interventions throughout their lives, which impose a high rate of morbidity and mortality. OBJECTIVE: To develop a less invasive technique for implantation of a valved prosthesis through the right ventricle. METHODS: The valved prosthesis consists of an auto expanding metal stent built with nitinol, surrounded with polyester, where the three leaflets of bovine pericardium were mounted. Twelve pigs were used to perform the implants. Echocardiographic control was performed immediately after implantation and one, four, eight and 12 weeks. RESULTS: One animal showed reflux of moderate to severe and three mild reflux. Transvalvular gradients measured before implantation ranged from 3 to 6 mmHg and that soon after the implant was increased, ranging from 7 to 45 mmHg. There was a decrease in these gradients during follow up and in only four of the twelve animals the gradients were above 20 mmHg. Thrombus formation occurred in the prosthesis of six animals, and this was the most frequent complication. CONCLUSION: These findings highlight the need for studies with the use of anticoagulants and antiplatelet, an attempt to reduce this event. The study aims to contribute for the start of the use of prosthetic heart valves that could be implanted through minimally invasive techniques without the use of cardiopulmonary bypass. PMID- 22086571 TI - Influence of respiratory muscle strength in evolution of patients with heart failure after cardiac surgery. AB - OBJECTIVE: To investigate the influence of preoperative respiratory muscle strength in postoperative pulmonary complications in patients with heart failure undergoing cardiac surgery. METHODS: From March 2009 to September 2010, 40 patients admitted to the cardiology service of the Fundacao de Beneficencia Hospital de Cirurgia were divided into two groups according to the values of maximal inspiratory pressure measured by manometer: Group A (n = 21), composed of patients with normal respiratory muscle strength, and Group B (n = 19), patients with reduced strength. After pre-operative evaluation, all patients underwent the surgical procedure and followed until hospital discharge by the same researcher, who recorded on data collection especially its evolution for the presence of pulmonary complications after surgery, which was divided general and specific. RESULTS: 19% of patients in group A and 31.6% of patients in group B had pulmonary complications overall, this difference was not statistically significant (P = 0.29). Regarding the presence of specific complications, group A was 14.3% and 10.5% group B (P = 0.55). There was also no difference in the days of ICU stay and total (ICU + ward) between groups. CONCLUSION: In this study, preoperative respiratory muscle dysfunction does not seem to influence the evolution of heart failure patients for the presence of pulmonary complications after cardiac surgery. PMID- 22086572 TI - Atrioventricular block in the postoperative period of heart valve surgery: incidence, risk factors and hospital evolution. AB - INTRODUCTION: Disturbances of the cardiac conduction system are potential complications after cardiac valve surgery. OBJECTIVES: This study was designed to investigate the association between perioperative factors and atrio-ventricular block, the need for temporary cardiac artificial pacing and, if necessary, permanent pacemaker implantation after cardiac valve surgery. METHODS: Retrospective analysis of the Cardiac Surgery Database - Hospital Sao Lucas/PUCRS. The data are collected prospectively and analyzed retrospectively. RESULTS: Between January 1996 and December 2008 were included 1102 valve surgical procedures: 718 aortic valves (65.2%), 407 (36.9%) mitral valve and 190 (17.2%) coronar artery bypass grafting combined with valve repair and 23 (2.1%) aortic and mitral combined surgery. 187 patients (17%) showed clinical and electrocardiographic pattern of atrio-ventricular block requiring artificial temporary pacing. Of these, 14 patients (7.5%) required permanent pacemaker implantation (1.27% of the total valve surgery patients). Multivariate analysis showed association of the incidence of atrio-ventricular block and temporary pacing with mitral valve surgery (OR 1,76; CI 95% 1.08-2.37; P = 0.002), implantation of bioprosthetic devices (OR 1.59; CI 95% 1.02-3.91; P = 0,039), age over 60 years (OR 1.99; CI 95% 1.352.85; P < 0.001), prior use of anti-arrhythmic drugs (OR 1.86; CI 95% 1.04-3.14; P = 0.026) and previous use of b-blocker (OR 1.76; CI 95% 1.25-2.54; P = 0.002). Remarkably the presence of atrio-ventricular block did not significantly show association with increased mortality, but significantly prolonged (P < 0.0001) hospital length-of-stay and, therefore, hospital costs. CONCLUSIONS: Our study presents a group of predictive factors referring to a specific patient profile by which high risk of atrio-ventricular block and the need of temporary cardiac pacing after cardiac valve surgery it is determined. PMID- 22086573 TI - The use of inhibitors of angiotensin-converting enzyme and its relation to events in the postoperative period of CABG. AB - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce the chance of death, myocardial infarction (MI) and cerebrovascular accident (CVA) in patients with coronary disease. However there is no consensus as to its indication in patients undergoing coronary artery bypass grafting (CABG). OBJECTIVE: To assess the relationship between preoperative use of ACE inhibitors and clinical outcomes after CABG. METHODS: Retrospective cohort study. We included data from 3,139 consecutive patients undergoing isolated CABG in Brazilian tertiary care hospital between January 1996 and December 2009. Follow-up was until discharge or death. Clinical outcomes after surgery were analyzed between users and nonusers of ACE inhibitors preoperatively. RESULTS: Fifty-two percent (n=1,635) of patients received ACE inhibitors preoperatively. The use of ACE inhibitors was an independent predictor of need for inotropic support (OR 1.24, 95% CI 1.01 to 1.47, P = 0.01), acute renal failure (OR 1.23, 95% CI 1.01 to 1.73, P = 0.04) and progression to atrial fibrillation (OR 1.32, 95% CI 1.02 to 1.7, P = 0.03) postoperatively. The mortality rate among patients receiving or not preoperative ACE inhibitors was similar (10.3% vs. 9.4%, P = 0.436), as well as the incidence of myocardial infarction and stroke (15.6% vs. 15.0%, P = 0.694 and 3.4% vs. 3.5%, P = 0.963, respectively). CONCLUSION: The use of preoperative ACE inhibitors was associated with increased need for inotropic support and higher incidence of acute renal failure and postoperative atrial fibrillation, not associated with increased rates of myocardial infarction, stroke or death. PMID- 22086574 TI - Long-term evolution of mitral commissurotomy in rheumatic patients with low echocardiographic score. AB - INTRODUCTION: The good results of open mitral commissurotomy are well known and there is a hypothesis that it could provide better results in patients selected by echocardiographic score. OBJECTIVE: The purpose of this study is to analyze the late results with open mitral commissurotomy in patients selected by score and to identify variables influencing these results. METHODS: From January 1990 to August 1994, 50 patients were submitted to open mitral commissurotomy due to rheumatic mitral stenosis in Heart Institute of University of Sao Paulo Medical School. Patients with age < 60 years, in functional class II, III or IV (New York Heart Association) and echocardiographic score 9 were included. The mean age was 32.7 +/- 8.3 years and 41 patients (82%) were female. The functional class was II in three patients (6%), III in 46 (92%) and IV in one (2%). Forty six patients (92%) were in sinus rhythm and four (8%) were in atrial fibrillation. The mean mitral valve area was 0.9 +/- 0.2 cm2. RESULTS: There was no hospital mortality. There were two late deaths, one related to valve disease. Actuarial survival was 95.5 +/- 3.1 %, freedom from reoperation was 62.3 +/- 11,8% and freedom from tromboembolism was 88,2 +/- 5,0% in 18 years. There was no endocarditis. The grade of the echocardiographic score had no significant influence on the reoperations in late evolution. CONCLUSION: Open mitral commissurotomy presented excelent long term results in rheumatic patients with low echocardiographic score. PMID- 22086575 TI - Validation of MagedanzSCORE as a predictor of mediastinitis after coronary artery bypass graft surgery. AB - OBJECTIVE: The aim of this study is to evaluate the applicability of a new score for predicting mediastinitis - MagedanzSCORE - in patients undergoing coronary artery bypass graft (CABG) surgery in the Division of Cardiovascular Surgery of Pronto Socorro Cardiologico de Pernambuco - PROCAPE. METHODS: Retrospective study involving 500 patients operated between May/2007 and April/2010. The registers contained all the information used to calculate the MagedanzSCORE. The outcome of interest was mediastinitis. We calculated sensitivity, specificity, positive predictive value, negative predictive value, concordance and accuracy. The accuracy of the model was evaluated by ROC (receiver operating characteristic) curve. RESULTS: The incidence of mediastinitis was 5.6%, with a lethality rate of 32.1%. In univariate analysis, the five variables of the MagedanzSCORE were predictors of postoperative mediastinitis: chronic obstructive pulmonary disease (OR 6.42; 95.0% CI 2.76-14.96; P<0.001), obesity (OR 3.06; 95.0% CI 1.32-7.09; P=0.009), surgical reintervention (OR 82.40; 95.0% CI 30.40-223.30; P<0.001), multiple transfusion (OR 3.33; 95.0% CI 1.52-7.29; P=0.003) and stable angina class IV or unstable (OR 2.59; 95.0% CI 1.19-7.64; P=0.016) according to Canadian Cardiovascular Society. The score had a sensitivity of 96.4%, specificity of 90.0%, positive predictive value of 36.5%, negative predictive value of 99.8% and 90.4% concordance. The accuracy measured by the area under the ROC curve was 96.2% (95.0% CI 94.5%-97.9%). CONCLUSIONS: The MagedanzSCORE proved to be a simple and objective index, revealing a satisfactory predictor of development of postoperative mediastinitis in patients undergoing CABG surgery at our institution. PMID- 22086576 TI - Transforming growth factor-beta/Smad signaling function in the aortopathies. AB - OBJECTIVES: Transforming growth factor (TGF)-beta/Smad signaling pathway in aortic dissection patients and normal subjects has not been previously described. The present study was designed to evaluate the TGF-beta/Smad signaling expressions in the patients with acute type A aortic dissection in comparison with those in the patients with thoracic aortic aneurysm and with coronary artery disease, and (or) the healthy subjects. METHODS: Consecutive surgical patients for acute type A aortic dissection (20 patients), aortic aneurysm (nine patients) or coronary artery disease (20 patients) were selected into this study. Blood samples (4 ml) were obtained from the right radial arterial indwelling catheter after systemic heparinization prior to the start of cardiopulmonary bypass in the operating room. Twenty-one young healthy volunteers without underlying health issues who donated forearm venous blood samples (4 ml) were taken as control. The surgical specimens of the aortic tissues were obtained immediately after they were severed during the operations of the replacement of the aorta in the patients with aortic dissection or aortic aneurysm. In patients receiving coronary artery bypass grafting, the tiny aortic tissues were taken when the punch holes of the proximal anastomosis on the anterior wall of the ascending aorta were made. The aortic tissues were for RNA, protein, or supernatant preparations until detection of TGF-beta1 mRNA by quantitative real-time reverse transcription polymerase chain reaction, of TGF-beta1, TGF-beta receptor I, Smad2/3, Smad4 and Smad7 by Western blot, and of TGF-beta1 by enzyme-linked immunosorbent assay, respectively. In particular, the linear correlations of the relative grayscales between different proteins of each group, and those correlations between the quantitative TGF-beta1 by enzyme-linked immunosorbent assay and the time interval from the onset to surgery or the maximal dimensions of the aorta of the aortic dissection group were assessed. RESULTS: Quantitative real-time reverse transcription polymerase chain reaction showed that TGF-beta1 mRNA were upregulated in all surgical groups (1.59 +/- 0.33 vs. 1.45 +/- 0.34 vs. 1.48 +/- 0.48, P > 0.05). Western blot revealed that the expressions of TGF beta1, TGF-beta receptor I, Smad2/3, Smad4 and Smad7 were positive in the aortic tissues of all three investigated groups. Of the quantitative relative grayscales, a significant reverse correlation was noted between TGF-beta1 and Smad2/3 (Y = -0.8552X + 1.6417, r = -0.759, P < 0.0001), and a close direct correlation between Smad4 and Smad7 (Y = 0.5905X + 0.2805, r = 0.781, P < 0.0001) in the Aortic Dissection Group. In the Aortic Aneurysm Group, Smad4 and Smad7 were also closely correlated (Y = 0.5228X + 0.1642, r = 0.727, P = 0.026), and in the Coronary Artery Disease Group, TGF-beta1 and Smad7 were much significantly correlated (Y = 0.5301X + 0.5758, r = 0.917, P = 0.004). By enzyme-linked immunosorbent assay, TGF-beta1 level of the aortic tissue was lower in the aortic dissection than in the aortic aneurysm and coronary artery disease groups with no statistical significance (319.52 +/- 129.21 pg/mg protein vs. 324.09 +/- 49.70 pg/mg protein vs. 304.15 +/- 29.39 pg/mg protein, P > 0.05). The plasma TGF-beta1 levels were 1158.30 +/- 11.54 pg/ ml, 1170.27 +/- 8.26 pg/ml, 1225.00 +/- 174.42 pg/mL and 1160.25 +/- 13.01 pg/mL in the four groups, respectively, showing significant intergroup differences (P < 0.05). No significant correlation was found between the aortic or plasma TGF-beta1 levels and the time interval from the onset to surgery or the maximal dimensions of the aorta in the patients of the aortic dissection group. CONCLUSIONS: Aortic dissection, aortic aneurysm and atheroslerosis might be associated with an enhanced TGF beta/Smad signaling function, with aortic dissection exhibiting a less prominent upregulation. It might have implications for downstream signal activation presumably translating into matrix degradation in the condition of aortic dissection in comparison to matrix deposition in aortic aneurysm and coronary artery disease. PMID- 22086577 TI - Plasmatic vasopressin in patients undergoing conventional infra-renal abdominal aorta aneurysm repair. AB - OBJECTIVES: To evaluate plasmatic arginine vasopressin (AVP) levels in patients undergoing scheduled conventional abdominal aortic aneurysm (AAA) repair. METHODS: Plasmatic AVP concentrations were measured by radioimmunoassay in 22 non consecutive adult patients undergoing infra-renal AAA repair. They were under combined general and epidural anesthesia at the following time frames: 1--pre operative (T0); 2--2h (T1) and 6h (T2) after the surgical procedure; 3--in the morning at the first (T3), second (T4) and third (T5) post-operative days. Some clinical and laboratory variables were also recorded. RESULTS: The mean age of patients was 68 +/- 10 years; 17 were males. Plasmatic AVP (mean +/- SD; pg/mL) was within the normal range at T0 (1.4 +/- 0.7; baseline), increasing significantly at T1 (62.6 +/- 62.9; P<0.001) and at T2 (31.5 +/- 49.7; P<0.001), with a progressive fall, returning to basal levels at T5 (2.1 +/- 3.8; P = NS). Positive and statistically significant correlations were found between AVP and glycemia, serum lactate and white blood cells counts, but not with systemic arterial pressure or plasma osmolarity during the postoperative period. CONCLUSIONS: Considering that no correlations were found between AVP levels and hemodynamic or plasmatic osmolarity variations in AAA repair, it seems that stress response is mainly secondary to noxious stimulation mediated by the autonomic nervous system that is not completely blocked by anesthetics. PMID- 22086578 TI - Parents' knowledge of infective endocarditis in children with congenital heart disease. AB - INTRODUCTION: The guidelines to prophylaxis of infectious endocarditis changed, but many congenital heart diseases continue to be considered as high risk for the development of the disease. OBJECTIVE: To evaluate the knowledge of parents or guardians of children and adolescents with congenital heart disease seen at a referral center in Rio Grande do Sul, Brazil on infective endocarditis and its prevention. METHODS: Cross-sectional study with 90 patients with congenital heart defects in regular outpatient treatment. The parents' knowledge was assessed using a specific questionnaire and other data were obtained through medical records. RESULTS: The median age of patients was 5.6 years (3 months -14 years), being 57,7% males. The median follow-up time in service was 3.49 years (1.20 7.38). The years of formal schooling of the parents had a mean of 7.67 +/- 3.25 years. According to the score previously established, the knowledge of the interviewed parents was considered satisfactory in 37.7%, regular in 33.3% and unsatisfying in 28,8%. There was significant correlation between the index of parents' knowledge and monitoring of children at service (r=0.584; P=0.796). There was no correlation between parents' education and knowledge of them (r=0.028; P=0.796). CONCLUSION: The parents' knowledge about endocarditis and its prevention was inadequate, requiring greater attention to the orientations passed in consultations. PMID- 22086579 TI - Decellularization as an anticalcification method in stentless bovine pericardium valve prosthesis: a study in sheep. AB - OBJECTIVE: The objective was to analyze the decellularization process with SDS in glutaraldehyde-preserved bovine pericardium as an anticalcification method in a circulatory sheep model. METHODS: The valved tubs were implanted in pulmonary artery position in sheep by 180 days. The animals were divided in two groups of 8 animals: control group--glutaraldehyde-preserved bovine pericardium and the study group--decellularized bovine pericardium with 0,1% SDS and glutaraldehyde preserved. After explantation the tubs were analized by x-ray macroscopy, hematoxilin-eosin, alizarin-red and Russel-Movatz pentacromic histology. The calcium content was measured by flame atomic absorption spectrometry. RESULTS: There was no early mortality, but two animals in each group died during the study. All cusps in the control group were severely calcified and in some points in the conduits, while the decellularized group did not show macroscopic calcification. Data were proved by x-ray and histologycal exams. The matrix was preserved in histologycal analysis in decellularized group, without gross calcification. The wall conduits calcium content was 35,25 +/- 42,13 ug/mg in the control group versus 15,75 +/- 10,44 ug/mg in the decellularized one: in the cusps was 264,4 +/- 126,16 ug/mg in control group versus 94,29 +/- 27,05 ug/mg in decellularized group (P = 0,009). CONCLUSION: The decellularization with 0.1% SDS was effective as an anticalcification method in bovine pericardial grafts implanted in a sheep circulatory model for 180 days. PMID- 22086580 TI - Adiponectin expression in epicardial adipose tissue after percutaneous coronary intervention with bare-metal stent. AB - BACKGROUND: The classical view of adipose tissue as a passive reservoir for energy storage is no longer valid. In the past decade, adipose tissue has been shown to have endocrine functions and the most abundant peptide secreted by adipocytes is adiponectin. Pericardial adipose tissue (PAT) is distributed around coronary arteries and endovascular injury, caused by the presence of intracoronary bare-metal stent (BMS), could promote inflammatory changes in the periadvential fat, contributing to vascular restenosis. OBJECTIVE: We sought to determine gene expression of inflammatory mediator in pericardial adipose tissue after bare-metal stent implantation and vascular restenosis that had been referred to operative treatment. METHODS: Paired samples of PAT were harvested at the time of elective coronary artery bypass surgery (CABG) in 11 patients (n = 22), one sample was obtained of the tissue around BMS area and another sample around coronary artery without stent. Local expression of adiponectin was determined by real-time polymerase chain reaction (RT-PCR) using Taq DNA polymerase. RESULTS: In two samples, there was no gene expression of adiponectin. We are able to identify adiponectin in 20 samples, however, the pattern of gene expression were heterogeneous.We did not notice specificity when we compared PAT obtained near BMS area or far from BMS area. CONCLUSION: There were no correlation between adiponectin gene expression and presence of BMS. PMID- 22086581 TI - Pantoprazole provides myocardial protection similar to ischemic preconditioning: experimental study of isolated hearts of rats. AB - OBJECTIVE: To evaluate pantoprazole effect in the functional recovery of isolated hearts of rats, submitted to ischemia and reperfusion with and without ischemic preconditioning. METHODS: In four groups of eight Wistar breed rats, the hearts were removed after anesthesia and perfused with Krebs-Henseleit solution (95% O2, 5% CO2, 37 oC). GI, GII, GIII and GIV hearts were submitted to ischemia (20 min) and reperfusion (30 min). In GII and GIV, preconditioning was performed with 5 min of ischemia and 5 min of reperfusion before 20 min of the ischemia period induction. In GIII and GIV pantoprazole 100 mg was done before a 20 min-period of ischemia induction. Heart Rate (HR), Coronary Flow (CoF), Systolic Pressure (SP), +dP/dt and -dP/dt were registered before (t0) and after reperfusion (t30). Kruskal-Wallis (P<0.05) test was used. RESULTS: There were no differences (P>0.05) between groups among HR and CoF values. Differences occurred between groups, I and II, III and IV at t30 with SP reduced for 32% mean value in GI, 65% GII, 65% GIII, and 73% GIV; The t30 + dP/dtmax were 34% in GI, 61% GII, 63% GIII and 72% GIV. The t30 -dP/dtmax were GI 28%, GII 63%, GIII 75 % and GIV 75%; (P<0.05). There were no significant differences in the SP, +dP/dtmax, and dP/dtmax between Groups II, III and IV results. CONCLUSIONS: The administration of pantoprazole before induction of ischemia significantly protected the myocardial functional recovery with the results of SP, + dP / dtmax and dP/dtmax similar to the ischemic preconditioning against ischemia-reperfusion. PMID- 22086582 TI - Absence of arteriosclerosis in intramyocardial coronary arteries: a mystery to be solved? AB - Several studies show that portions of intramyocardial coronary arteries are spared of arteriosclerosis, involving morphological, embryological, biochemical and pathophysiological aspects. Endothelial function is significantly affected in the segment of transition, as estimated by the vasoactive response to Ach. These findings suggest that myocardial bridge can provide protection against arteriosclerosis by counteracting the negative effects of endothelial dysfunction. The intramyocardial portion's protection phenomenon deserves further scientific research on all research fronts. Improved morphological, biomechanical and especially physiological and embryological knowledge may be the key to a future window of opportunity for chronic arterial disease therapy and prevention. In addition, this review discusses possible therapeutic approaches for symptomatic coronary ischemia caused by myocardial bridges. PMID- 22086583 TI - Surgical treatment of atrial fibrillation: integrative review. AB - When atrial fibrillation (AF) is present in pre-operative open heart surgeries, including coronary artery bypass grafting and valve operations, it represents an independent risk factor for cardiac events and reduced survival. Due to the complexity of the subject, especially when evaluating success rates (reversion and maintenance of normal sinus rhythm), a consensus statement was recently proposed by the International Society of Minimally Invasive Cardiothoracic Surgery (ISMICS), in order to determine whether the intraoperative ablation of AF promotes favorable clinical outcomes in patients undergoing other cardiac operations in comparison with individual operations without ablation. The aim of this paper is to present published data which has contributed to consensus statement and can be useful as update source. The integrative review was the methodology that provides synthesis of knowledge and applicability of results of significant studies about presented topic. PMID- 22086584 TI - Respiratory physiotherapy in the pre and postoperative myocardial revascularization surgery. AB - The cardiovascular diseases are among the main death causes in the developed world. They have been increasing epidemically in the developing countries. In spite of several alternatives for the treatment of the coronary artery disease; the surgery of the myocardial revascularization is an option with proper indications of medium and long-term with good results. It provides the remission of the angina symptoms contributing to the increase of the expectation and improvement of the life quality. Most of patients undergoing myocardial revascularization surgery develop postoperative lung dysfunction with important reduction of the lung volumes, damages in the respiratory mechanism, decrease in the lung indulgence and increase of the respiratory work. The reduction of volumes and lung capacities can contribute to alterations in the gas exchanges, resulting in hypoxemia and decrease in the diffusion capacity. Taking this into account, the Physiotherapy has been requested more and more to perform in the pre as well as in the postoperative period of this surgery. This study aimed at updating the knowledge regarding the respiratory physiotherapy performance in the pre and postoperative period of the myocardial revascularization surgery enhancing the prevention of lung complications. The Physiotherapy uses several techniques in the preoperative period; such as: the incentive spirometry, exercises of deep breathing, cough, inspiratory muscle training, earlier ambulation and physiotherapeutic orientations. While in the postoperative period, the objective is the treatment after lung complications took place, performed by means of physiotherapeutic maneuvers and noninvasive respiratory devices, aiming at improving the respiratory mechanism, the lung reexpansion and the bronchial hygiene. Respiratory physiotherapy is an integral part in the care management of the patient with cardiopathy, either in the pre or in the postoperative period, since it contributes significantly to a better prognosis of these patients with the use of specific techniques. PMID- 22086585 TI - Near-fatal pulmonary embolism in an experimental model: hemodynamic, gasometric and capnographic variables. AB - INTRODUCTION: Experimental studies on pulmonary embolism (PE) are usually performed under mechanical ventilation. Most patients with suspicion of PE enter the Emergency Services in spontaneous breathing and environmental air. Thus, under these conditions, measurements of hemodynamic, gasometric and capnographic variables contribute largely to a more specific comprehension of cardiopulmonary and gasometric alterations in the acute phase of the disease. Studies which evaluated animals under conditions are lacking. OBJECTIVE: This study aimed to submit animals under spontaneous ventilation and without supplemental oxygen to PE. METHODS: PE was induced in six pigs using autologous blood clots, and cardiorespiratory and gasometric records were performed before and after PE. The values of "near fatal" mean pulmonary arterial pressure (MPAP) were previously determined. RESULTS: The presence of obstructive shock could be evidenced by increased MPAP (from 17.8 +/- 3.5 to 41.7 +/- 3.3 mmHg) (P<0.0001) and decreased cardiac output (from 4.9 +/- 1.0 to 2.7 +/- 1.0 L/min) (P<0.003). Consequently, metabolic acidosis occurred (Lac art) (from 2.4 +/- 0.6 to 5.7 +/- 1.8 mmol/L)(P<0.0001). It was observed hypoxemia (from 73.5 +/- 12.7 to 40.3 +/- 4.6 mmHg) (P<0.0001); however, PaCO2 did not vary (from 44.9 +/- 4.4 to 48.2 +/- 6.0 mmHg) (NS). There were significant increases in both P(a-et)CO2 (from 4.8 +/- 2.8 to 37.2 +/- 5.8 mmHg) and P(A-a)O2 (from 8.2 +/- 8.9 to 37.2 +/- 10.3 mmHg) (both P<0.0001). There was also a significant increase in the total alveolar minute volume (from 4.0 +/- 0.9 to 10.6 +/- 2.9 L/min) (P<0.0001). CONCLUSIONS: In this model, the near fatal MPAP was from 2 to 2.5 times the basal MPAP; and the capnographic variables, associated with arterial and venous gasometry, showed effective in discriminating an acute obstructive profile. PMID- 22086586 TI - Experimental model of myocardial infarction induced by isoproterenol in rats. AB - OBJECTIVE: To evaluate and validate, in our laboratory, the essay of myocardial infarction induced by isoproterenol in rats by means of analysis of hematological, biochemical, oxidative stress markers and histopathological parameters. METHODS: Thirty young, male, Wistar rats (145 to 230 g) were randomly allocated in two groups: Sham group, which underwent a virtual myocardial infarction induction, and the Infarction group, which underwent a myocardial infarction induction with isoproterenol. The administrations for the infarction induction were performed during two consecutive days and a 24-hour interval between them. Twenty-four hours after the last administration, rats from both groups were anesthetized and sacrificed for blood sample collection to evaluate complete blood count (CBC) and biochemical parameters (SGOT, SGPT, troponin I, urea and creatinin), obtain myocardial fragments for oxidative stress markers analyses (catalase activity and glutathione concentrations) as well as histopathological examinations. RESULTS: There were no death cases in the Sham group, while the mortality rate in the Infarction group was 25%. Myocardial infarction induction with isoproterenol raised leukocytes and neutrophils counts, SGOT, troponin I and urea concentrations, reduced catalase enzyme activity and glutathione concentrations in the myocardium and let to histopathological concentrations as well. It did not exert alterations in terms of hemoglobin, SGPT and creatinin concentrations. CONCLUSIONS: The isoproterenol-induced myocardial infarction essay in rats was adequately reproduced in our laboratory, causing alterations in hematological, biochemical, oxidative stress markers and histopathological parameters. PMID- 22086587 TI - Endovascular repair of ascending aorta and coronary stent implantation. AB - Endovascular treatment of ascending aorta pseudoaneurysms with coronary stents implantation at the same procedure was feasible, although longer followup is necessary. PMID- 22086588 TI - Terminal ischemic cardiomyopathy associated with complication of stenting in the treatment of acute myocardial infarction. AB - A serious complication such as dissection of the left main coronary artery, with significant reduction in coronary blood flow by the true light, requires quick action. Therefore, the immediate choice of stent with appropriate length and size to treat the complication is necessary. PMID- 22086589 TI - Geli Putty(r): a new alternative on sternal hemostasis in cardiac surgery. AB - We present a gelatin that fills the medullary of sternum providing effective hemostasis plus protection for each sternal end. PMID- 22086590 TI - Lymphoscintigraphic changes after harvesting of the saphenous vein for coronary artery bypass graft. AB - Bridged incisions do not eliminate lesions to the lymphatic vessels and so the identification of risk factors associated to lymphatic lesions is important. PMID- 22086591 TI - Effects of cryopreservation and/or decellularization on extracellular matrix of porcine valves. AB - The objective of this study was to evaluate the morphology of decellularized and/or cryopreserved porcine pulmonary valves, to determine a solution capable of completely remove the cells without damaging the extracellular matrix. Porcine pulmonary valves were incubated for 24 hs in sodium deoxicholate 1% or sodium dodecyl sulfate 0.1 and 0.3%, with or without associated cryopreservation. Evaluation was done with optical microscopy (Hematoxilin-Eosin, Acetic Orcein and Gomori) and with morphometric analysis. The effectiveness of the solutions was variable, but the best results were obtained with the sodium dodecyl sulfate solution 0.1%. PMID- 22086592 TI - Multiple left atrial myxoma: case report. AB - Primary cardiac tumors are infrequent, with an incidence between 0.001% and 0.2%, mostly comprising benign histological characteristics in 75% of these cases. Myxomas account for approximately 50% of these neoplasms. As regards location, 75 80% of myxomas are in the left atrium, 18% in the right atrium, and more rarely in the ventricles. We report a case of a patient in functional class (FC) IV New York Heart Association (NYHA) and postoperative histological diagnosis of multilobular myxoma originating in the posterior left atrial wall. Clinical evaluation 3 months after surgery suggested NYHA functional class I and echocardiographic absence of intracardiac masses. PMID- 22086593 TI - Calcified amorphous tumor of the heart: case report. AB - Calcified amorphous tumor of the heart consists of a cardiac mass of rare nonneoplastic nature that mimics malignancy and causes symptoms due to obstruction or embolization of calcific fragments. We present a case of tumor 17 year-old young, male, in tricuspid valve, with classic pathological findings. It was preferred to approach for classic median esternotomy, installation of the circuit of extracorporal circulation and right atriotomy, exereses of tumor, DeVega's plasty in tricuspid valve and bicuspidization. The amatomopathological study demonstrated presence of extensive calcification and metaplastic bone areas. The patient had an uneventful hospitalization. PMID- 22086594 TI - A large pericardial cyst presenting with compression of the right-side cardiac chambers. AB - Pericardial cysts are rare, usually congenital. Cysts frequently occur in the right cardiophrenic angle and their diagnosis is usually suspected after an abnormal chest X ray. The present case report shows a case of pericardial cyst with atypical radiographic aspect in an athletic patient who presented clinical with symptoms of right ventricular failure. The diagnosis was suggested by echocardiogram and subsequently was confirmed by pathologic examination. PMID- 22086595 TI - Migration of a Kirschner wire into the thoracic ascendent aorta artery. AB - The orthopedic metallic pins and wires migration for the chest cavity is uncommon and rarely reported in medical literature although it is potentially lethal, especially when they reach the heart or mediastinum great vessels. We reported a case of Kirschner wire withdrawal, for right postero-lateral thoracotomy, which were transfixating ascendent thoracic aorta artery, in its due to its migration of left clavicle, where it was placed to fix an occurred fracture 10 years before. PMID- 22086596 TI - Checklist in pediatric cardiac surgery in Brazil: an useful and necessary adaptation of the Quality Improvement Collaborative International Congenital Heart Surgery in Developing Countries. PMID- 22086597 TI - Cognitive dysfunction after cardiac surgery: a relevant issue. PMID- 22086598 TI - After the impact factor, the DOI. PMID- 22086599 TI - Myocardial revascularization without cardiopulmonary bypass: historical background and thirty-year experience. PMID- 22086600 TI - Terminal ischemic cardiomyopathy associated to stent extrusion to the aortic lumen. PMID- 22086601 TI - Quality of valve prostheses: are we treating our patients well in the Brazilian National Health System? PMID- 22086603 TI - CS-US interval determines the transition from overshadowing to potentiation with flavor compounds. AB - The present series of five flavor aversion experiments with rat subjects examined compound conditioning at varying CS-US intervals. Using a taste-taste design, Experiments 1A and 1B demonstrated overshadowing at a 0-min CS-US interval and potentiation at a 120-min CS-US interval, and these effects occurred with both tastes of the compound. Experiment 2 showed that the aversion to a single element is reduced when the CS-US interval is increased to 120 min, but the aversion for a compound taste is not. Experiments 3A and 3B explored odor + taste compound conditioning; the results demonstrated odor potentiation across the trace interval and a transition from taste overshadowing to taste potentiation. Collectively, the data show that the change from overshadowing to potentiation was not due to changes in the aversions produced by compound conditioning but, instead, was due to a more rapid loss of conditionability across a trace interval prior to the US in single-element conditioning. These experiments suggest that following compound conditioning, the aversion to each element represents generalization decrement from the configured compound, but the designation of overshadowing or potentiation actually depends on the status of conditioning in the single-element control. PMID- 22086602 TI - RNA helicase DDX5 regulates microRNA expression and contributes to cytoskeletal reorganization in basal breast cancer cells. AB - RNA helicase DDX5 (also p68) is involved in all aspects of RNA metabolism and serves as a transcriptional coregulator, but its functional role in breast cancer remains elusive. Here, we report an integrative biology study of DDX5 in breast cancer, encompassing quantitative proteomics, global MicroRNA profiling, and detailed biochemical characterization of cell lines and human tissues. We showed that protein expression of DDX5 increased progressively from the luminal to basal breast cancer cell lines, and correlated positively with that of CD44 in the basal subtypes. Through immunohistochemistry analyses of tissue microarrays containing over 200 invasive human ductal carcinomas, we observed that DDX5 was up-regulated in the majority of malignant tissues, and its expression correlated strongly with those of Ki67 and EGFR in the triple-negative tumors. We demonstrated that DDX5 regulated a subset of MicroRNAs including miR-21 and miR 182 in basal breast cancer cells. Knockdown of DDX5 resulted in reorganization of actin cytoskeleton and reduction of cellular proliferation. The effects were accompanied by up-regulation of tumor suppressor PDCD4 (a known miR-21 target); as well as up-regulation of cofilin and profilin, two key proteins involved in actin polymerization and cytoskeleton maintenance, as a consequence of miR-182 down-regulation. Treatment with miR-182 inhibitors resulted in morphologic phenotypes resembling those induced by DDX5 knockdown. Using bioinformatics tools for pathway and network analyses, we confirmed that the network for regulation of actin cytoskeleton was predominantly enriched for the predicted downstream targets of miR-182. Our results reveal a new functional role of DDX5 in breast cancer via the DDX5->miR-182->actin cytoskeleton pathway, and suggest the potential clinical utility of DDX5 and its downstream MicroRNAs in the theranostics of breast cancer. PMID- 22086604 TI - Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2. AB - Pontocerebellar hypoplasia type 6 (PCH6) (MIM #611523) is a recently described disorder caused by mutations in RARS2 (MIM *611524), the gene encoding mitochondrial arginyl-transfer RNA (tRNA) synthetase, a protein essential for translation of all mitochondrially synthesised proteins. This case confirms that progressive cerebellar and cerebral atrophy with microcephaly and complex epilepsy are characteristic features of PCH6. Additional features of PCH subtypes 2 and 4, including severe dystonia, optic atrophy and thinning of the corpus callosum, are demonstrated. Congenital lactic acidosis can be present, but respiratory chain dysfunction may be mild or absent, suggesting that disordered mitochondrial messenger RNA (mRNA) translation may not be the only mechanism of impairment or that a secondary mechanism exists to allow some translation. We report two novel mutations and expand the phenotypic spectrum of this likely underdiagnosed PCH variant, where recognition of the characteristic neuroradiological phenotype could potentially expedite genetic diagnosis and limit invasive investigations. PMID- 22086606 TI - Unexpected electron transfer in cryptochrome identified by time-resolved EPR spectroscopy. AB - Subtle differences in the local sequence and conformation of amino acids can result in diversity and specificity in electron transfer (ET) in proteins, despite structural conservation of the redox partners. For individual ET steps, distance is not necessarily the decisive parameter; orientation and solvent accessibility of the ET partners, and thus the stabilization of the charge separated states, contribute substantially. PMID- 22086607 TI - The safe gate to the posterior paranasal sinuses: reassessing the role of the superior turbinate. AB - Surgery of the posterior ethmoid and sphenoid sinuses can be challenging. In 1999, a technique was described for identification of the superior turbinate and utilizing it as a landmark in endoscopic posterior ethmoidectomy and sphenoidotomy. Although this was more than a decade ago, it has not been supported by further studies. In our practice, we have routinely adopted this technique, and have modified it to allow further orientation during endoscopic surgery of the posterior sinuses. To describe a review of our technique, and to prospectively assess the value of the superior turbinate as a useful landmark during endoscopic posterior ethmoidectomy and sphenoidotomy. Fifty patients listed for endoscopic posterior ethmoidectomy with or without sphenoidotomy were included in a prospective study utilising our surgical technique. Data were collated for the success or failure of identification of the landmarks, and for any complications during the surgery. A total of 93 sides of endoscopic posterior ethmoidectomy and 73 sides of endoscopic sphenoidotomy were performed. The superior turbinate was identified in 100% of the cases. The coronal part of the superior turbinate basal lamella was identified in 60.22% of the cases, and the axial part in 88.17% of the cases. The natural sphenoid ostium was identified medial to the posterior part of the superior turbinate in 98.63% of the cases. The axial part of the superior turbinate basal lamella was a constant landmark for the level of the sphenoid ostium. The number of transverse septae between the axial part of the superior turbinate basal lamella and the skull base was studied, and was found never to exceed one septum. No major complications were recorded. One case of small posterior septal perforation was detected with no post-operative effects. Our study represents the first report of identifying the two parts of the superior turbinate basal lamella intra-operatively. It also represents the first report of using the axial basal lamella of the superior turbinate as a landmark for the level of the sphenoid sinus ostium, as well as a landmark for the level of the skull base. The superior turbinate represents a constant landmark for performing a safe posterior ethmoidectomy and sphenoidotomy. PMID- 22086609 TI - Hospice eligibility in patients who died in a tertiary care center. AB - BACKGROUND: Hospice is a service that patients, families, and physicians find beneficial, yet a majority of patients die without receiving hospice care. Little is known about how many hospitalized patients are hospice eligible at the time of hospitalization. METHODS: Retrospective chart review was used to examine all adult deaths (n = 688) at a tertiary care center during 2009. Charts were selected for full review if the death was nontraumatic and the patient had a hospital admission within 12 months of the terminal admission. The charts were examined for hospice eligibility based on medical criteria, evidence of a hospice discussion, and hospice enrollment. RESULTS: Two hundred nine patients had an admission in the year preceding the terminal admission and a nontraumatic death. Sixty percent were hospice eligible during the penultimate admission. Hospice discussions were documented in 14% of the hospice-eligible patients. Patients who were hospice eligible had more subspecialty consults on the penultimate admission compared to those not hospice eligible (P = 0.016), as well as more overall hospitalizations in the 12 months preceding their terminal admission (P = 0.0003), and fewer days between their penultimate admission and death (P = 0.001). CONCLUSION: The majority of terminally ill inpatients did not have a documented discussion of hospice with their care provider. Educating physicians to recognize the stepwise decline of most illnesses and hospice admission criteria will facilitate a more informed decision-making process for patients and their families. A consistent commitment to offer hospice earlier than the terminal admission would increase access to community or home-based care, potentially increasing quality of life. PMID- 22086608 TI - Cytochrome c signalosome in mitochondria. AB - Cytochrome c delicately tilts the balance between cell life (respiration) and cell death (apoptosis). Whereas cell life is governed by transient electron transfer interactions of cytochrome c inside the mitochondria, the cytoplasmic adducts of cytochrome c that lead to cell death are amazingly stable. Interestingly, the contacts of cytochrome c with its counterparts shift from the area surrounding the heme crevice for the redox complexes to the opposite molecule side when the electron flow is not necessary. The cytochrome c signalosome shows a higher level of regulation by post-translational modifications-nitration and phosphorylation-of the hemeprotein. Understanding protein interfaces, as well as protein modifications, would puzzle the mitochondrial cytochrome c-controlled pathways out and enable the design of novel drugs to silence the action of pro-survival and pro-apoptotic partners of cytochrome c. PMID- 22086610 TI - Examination of CD26/DPPIV, p53, and PTEN expression in thyroid follicular adenoma. AB - Tumor cytology has proven to be inadequate for precise diagnosis of thyroid follicular adenoma. This suggests the need for a molecular approach for its diagnosis. Expression of CD26/DPPIV (dipeptidyl peptidas IV), p53, and PTEN was analyzed in smears or sections obtained from 19 patients with histologically proven thyroid follicular adenoma. Papanicolaou staining, CD26/DPPIV activity staining, and HE staining were performed and the specimens were observed morphologically. Immunohistochemical analysis using antibodies against p53 and PTEN was performed. Genetic mutation of PTEN exons was performed using the laser capture microdissection method. The nuclear area of the CD26/DPPIV-positive cells was significantly larger than that of the CD26/DPPIV-negative cells. p53 expression was not observed any specimen. PTEN expression was observed in 18 of 19 cases. DNA sequence analysis did not reveal mutations in exons 5-9 of PTEN in the immunohistochemically PTEN-negative case. In accordance with our previous reports, we found that observation of concomitant CD26-positive and PTEN-negative status in cases of follicular adenoma suggests a state close to follicular carcinoma or progression to cancer, thus warranting careful follow-up. PMID- 22086611 TI - Quercetin-3-methyl ether inhibits lapatinib-sensitive and -resistant breast cancer cell growth by inducing G(2)/M arrest and apoptosis. AB - Lapatinib, an oral, small-molecule, reversible inhibitor of both EGFR and HER2, is highly active in HER2 positive breast cancer as a single agent and in combination with other therapeutics. However, resistance against lapatinib is an unresolved problem in clinical oncology. Recently, interest in the use of natural compounds to prevent or treat cancers has gained increasing interest because of presumed low toxicity. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity. Here, we found that quercetin-3-methyl ether caused a significant growth inhibition of lapatinib sensitive and -resistant breast cancer cells. Western blot data showed that quercetin-3-methyl ether had no effect on Akt or ERKs signaling in resistant cells. However, quercetin-3-methyl ether caused a pronounced G(2)/M block mainly through the Chk1-Cdc25c-cyclin B1/Cdk1 pathway in lapatinib-sensitive and resistant cells. In contrast, lapatinib produced an accumulation of cells in the G(1) phase mediated through cyclin D1, but only in lapatinib-sensitive cells. Moreover, quercetin-3-methyl ether induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7, and poly(ADP-ribose) polymerase (PARP) in both cell lines. Overall, these results suggested that quercetin-3-methyl ether might be a novel and promising therapeutic agent in lapatinib-sensitive or -resistant breast cancer patients. PMID- 22086612 TI - Pt and Pd in sediments from the Pearl River Estuary, South China: background levels, distribution, and source. AB - PURPOSE: This study assessed the concentrations of platinum (Pt) and palladium (Pd) in surface sediments and sedimentary cores collected from the Pearl River Estuary with a view of evaluating the distribution, background levels, possible sources, and contamination level of anthropogenic Pt and Pd. MATERIALS AND METHODS: Thirty-six samples of surface sediments and 12 samples from sedimentary cores were collected. Al(2)O(3) was analyzed on fused glass disks by X-ray fluorescence spectrometer. Heavy metal elements were measured by inductively coupled plasma-mass spectrometry. Pt and Pd were separated from the sample matrix by anion exchange chromatography and subsequent solvent extraction after samples had been digested in Carius tubes using aqua regia. The analysis of Pt and Pd was performed by isotopic dilution-inductively coupled plasma-mass spectrometry. RESULTS AND DISCUSSION: Pt and Pd concentrations in surface sediments were 0.28 2.11 and 0.39-38.30 ng/g, respectively, and Pt and Pd concentrations in sedimentary cores were 0.19-1.18 and 0.15-1.76 ng/g, respectively. Background values of Pt and Pd were 0.20-1.17 and 0.10-1.34 ng/g, respectively. The spatial distribution of the enrichment factor differed between Pt and Pd in surface sediments. Down-core variations in Pt, Pd, and other heavy metal elements were similar in all cases and were related to sediment type. CONCLUSIONS: Some of the Pt and Pt in surface samples were derived from anthropogenic emissions. Pt and Pd were delivered to the sediment by fluvial input. In addition to vehicle exhaust catalysts, Pt and Pd were derived from other sources (e.g., industrial process). An important post-burial remobilization process of Pt and Pd is likely to be particle mixing by billows caused by typhoon. PMID- 22086613 TI - Unilateral basal-ganglia involvement likely due to valproate-induced hyperammonemic encephalopathy. AB - A male child suffering from generalized tonic clonic epilepsy, on treatment with valproate, developed fulminant hepatic failure, hyperammonemia and encephalopathy due to drug toxicity. The most extraordinary feature was his MRI (FLAIR image) of brain which showed unilateral hyperintensities in right putamen and caudate nucleus. The patient recovered on withdrawal of valproate with mild residual left sided athetotic movements during remission. Repeat investigation confirmed an improved MRI imaging and normalised blood ammonia levels. The case report is unique because of unilateral involvement of basal ganglia due to valproate induced encephalopathy. PMID- 22086614 TI - Phase 2 trial of irinotecan and thalidomide in adults with recurrent anaplastic glioma. AB - BACKGROUND: Therapeutic options for patients with anaplastic gliomas (AGs) are limited despite better insights into glioma biology. The authors previously reported improved outcome in patients with recurrent glioblastoma treated with thalidomide and irinotecan compared with historical controls. Here, results of the AG arm of the study are reported, using this drug combination. METHODS: Adults with recurrent AG previously treated with radiation therapy, with Karnofsky performance score >=70, adequate organ function and not on enzyme inducing anticonvulsants were enrolled. Treatment was in 6-week cycles with irinotecan at 125 mg/m(2) weekly for 4 weeks followed by 2 weeks off, and thalidomide at 100 mg daily increased to 400 mg/day as tolerated. The primary endpoint was progression-free survival rate at 6 months (PFS-6), and the secondary endpoints were overall survival (OS) and response rate (RR). RESULTS: In 39 eligible patients, PFS-6 for the intent-to-treat population was 36% (95% confidence interval [CI] = 21%, 53%), median PFS was 13 weeks (95% CI = 6%, 28%) and RR was 10%(95% CI = 3%, 24%). Radiological findings included 2 complete and 2 partial responses and 17 stable disease. Median OS from study registration was 62 weeks, (95% CI = 51, 144). Treatment-related toxicities (grade 3 or higher) included neutropenia, diarrhea, nausea, and fatigue; 6 patients experienced venous thromboembolism. Four deaths were attributable to treatment-related toxicities: 1 from pulmonary embolism, 2 from colitis, and 1 from urosepsis. CONCLUSIONS: The combination of thalidomide and irinotecan did not achieve sufficient efficacy to warrant further investigation against AG, although a subset of patients experienced prolonged PFS/OS. A trial of the more potent thalidomide analogue, lenalidomide, in combination with irinotecan against AG is currently ongoing. PMID- 22086615 TI - Early cumulus cell removal could reduce the available embryo rate in human IVF. AB - PURPOSE: This study was designed to compare cumulus cell removal at different times and to evaluate their effects on embryo developmental potential and the outcomes of in vitro fertilization (IVF). METHODS: We retrieved 606 IVF cycles with standard long down regulation protocol from January 2010 to December 2010. These cycles were divided into two groups: group A, 364 cycles with high risk of fertilization failure, whose cumulus cells were removed 4 h after short gamete coincubation; group B, 242 cycles as control, whose cumulus cells removal were performed 17 to 18 h after insemination. The epidemiological, clinical, laboratory factors and the outcomes of these cycles were analyzed. RESULTS: The available embryo rate of group A was significantly lower (P = 0.002). There were no significant differences in other laboratory parameters and outcomes between the two groups (P > 0.05). CONCLUSIONS: For patients with high risk of fertilization failure, there could be a risk of compromising the rate of available embryos, if fertilization is judged by the presence of 2 PB by cumulus cell removal only 4 h post-insemination. Therefore, this strategy is not recommended to all IVF cycles and future studies are needed to confirm its reliability. PMID- 22086616 TI - Different ovarian response by age in an anti-Mullerian hormone-matched group undergoing in vitro fertilization. AB - BACKGROUND: Recently, serum anti-Mullerian hormone (AMH) has been used as a good marker of ovarian response during in vitro fertilization (IVF). However, in the clinical setting, we felt that ovarian response was clearly different by age with the same AMH level. Then in this study we evaluated the relationship between serum AMH, age and parameters related to ovarian response and compared these parameters in regard to age within serum AMH-matched group. METHODS AND RESULTS: The relationship of these parameters were evaluated retrospectively in patients undergoing their first IVF cycle under a GnRH agonist flare up protocol (n = 456) between October 2008 and October 2010 in our clinic. To understand the relations between variables described above, principal component analysis (PCA) was performed. PCA revealed patients' age was at the different dimension from serum AMH and other variables. Therefore at first we segregated all patients into Low, Normal and High responder groups by their serum AMH using cut-off value of receiver operator characteristics curve analysis. Secondary, we divided each responder group into four subgroups according to patients' age. The high aged subgroups required a significantly higher dose of gonadotropin and a longer duration of stimulation; however, they had significantly lower peak E2 and a smaller number of total oocytes as well as M2 oocytes compared to the low aged subgroups. CONCLUSIONS: The influence of aging on the ovarian response was clearly seen in all groups; the ovarian response tended to decrease as patients' age increased with the same AMH level. Therefore serum AMH in combination with age is a better indicator than AMH alone. PMID- 22086617 TI - Chemistry and physics of a single atomic layer: strategies and challenges for functionalization of graphene and graphene-based materials. AB - Graphene has attracted great interest for its superior physical, chemical, mechanical, and electrical properties that enable a wide range of applications from electronics to nanoelectromechanical systems. Functionalization is among the significant vectors that drive graphene towards technological applications. While the physical properties of graphene have been at the center of attention, we still lack the knowledge framework for targeted graphene functionalization. In this critical review, we describe some of the important chemical and physical processes for graphene functionalization. We also identify six major challenges in graphene research and give perspectives and practical strategies for both fundamental studies and applications of graphene (315 references). PMID- 22086618 TI - [Health economic evaluations: bringing together academia and policy]. PMID- 22086619 TI - [Evaluation of social and sanitary interventions: appraising the results to guide decisions]. PMID- 22086620 TI - [Cost-utility of the vaccine against the Human Papiloma Virus in Peruvian women]. AB - OBJECTIVES: To estimate the cost-utility of the vaccine against the Human Papiloma Virus (HPV) in peruvian women after the application of the vaccine at 10 years of age. MATERIALS AND METHODS: A cost-utility analysis was performed using the Markov's hidden model in a hypothetical cohort of peruvian women, based on the information on epidemiological parameters, costs associated to uterine cervical cancer (UCC) and the efficacy and costs of the vaccine against the HPV. The vaccination costs were estimated from the Peruvian Ministry of Health perspective and were compared against the quality-adjusted life years (QALYs), using a discount rate of 5%. RESULTS: The annual cost of the vaccination was USD 16,861,490, for the Papanicoau screening it was USD 3,060,793 and the costs associated to the UCC were USD 15,580,000. The incremental cost utility ratio (ICUR) was 6,775 USD/QALY. CONCLUSIONS: Vaccination against HPV can be cost utility compared to not vaccinating. PMID- 22086621 TI - [Cost analysis of rapid methods for diagnosis of multidrug resistant tuberculosis in different epidemiologic groups in Peru]. AB - OBJECTIVES: To evaluate the costs of three methods for the diagnosis of drug susceptibility in tuberculosis, and to compare the cost per case of Multidrug resistant tuberculosis (MDR TB) diagnosed with these (MODS, GRIESS and Genotype MTBDR plus(r)) in 4 epidemiologic groups in Peru. MATERIALS AND METHODS: In the basis of programmatic figures, we divided the population in 4 groups: new cases from Lima/Callao, new cases from other provinces, previously treated patients from Lima/Callao and previously treated from other provinces. We calculated the costs of each test with the standard methodology of the Ministry of Health, from the perspective of the health system. Finally, we calculated the cost per patient diagnosed with MDR TB for each epidemiologic group. RESULTS: The estimated costs per test for MODS, GRIESS, and Genotype MTBDR plus(r) were 14.83. 15.51 and 176.41 nuevos soles respectively (the local currency, 1 nuevos sol=0.36 US dollars for August, 2011). The cost per patient diagnosed with GRIESS and MODS was lower than 200 nuevos soles in 3 out of the 4 groups. The costs per diagnosed MDR TB were higher than 2,000 nuevos soles with Genotype MTBDR plus(r) in the two groups of new patients, and lower than 1,000 nuevos soles in the group of previously treated patients. CONCLUSIONS: In high-prevalence groups, like the previously treated patients, the costs per diagnosis of MDR TB with the 3 evaluated tests were low, nevertheless, the costs with the molecular test in the low- prevalence groups were high. The use of the molecular tests must be optimized in high prevalence areas. PMID- 22086622 TI - [Cost utility of renal transplant vs. hemodialysis in the treatment of end stage chronic kidney failure in a Peruvian hospital]. AB - OBJECTIVES: To assess and compare the cost utility of the cadaveric donor renal transplant (CDRT) at the Hospital Nacional Guillermo Almenara Irigoyen between 2000 to 2001, against haemodialysis (HD), 5 years after treatment initiation. MATERIALS AND METHODS: A cost utility study design was used, which evaluated every patient continuing treatment after 5 years of having the CDRT done, and 2 controls consisting in patients having received HD for 5 years, matched by age, sex and disease duration. The costs of each procedure and their Quality-adjusted life years (QALY's) were evaluated using the questionnaire of quality of life SF 36v2(TM), finally calculating the cost utility (CU) and incremental cost utility (ICU) ratios. RESULTS: Fifty-eight CDRT were performed between 2000-1. Five years later, 17 (29%) patients died and only 27 (47%) continued the treatment after CDRT. Out of the 31 patients (53%) having treatment failures, 26% rejected the transplant, 55% presented a complication and 19% were irregular. The mean SF 36v2(TM) scores obtained by the CDRT and HD patients were 95+/-12 and 87+/-18 points, respectively. The QALYs obtained by the CDRT and HD groups were 251 and 229 points, respectively; the CU ratios for the CDRT and HD were USD 11,984 and USD 9,243; and the ICU ratio for the period was USD 40,669. CONCLUSIONS: CDRTs performed during the years 2000-1 at the HNGAI, were 5 years later surprisingly less cost effective than the HD and CDRT's performed at year 2000 had a lower incremental cost utility ratio that those performed the 2001, probably because of the highest rate of irregular treatment. PMID- 22086623 TI - [Hip fracture in older adults: prevalence and costs in two hospitals. Tabasco, Mexico, 2009]. AB - OBJECTIVES: To determine hip fracture prevalence and direct healthcare costs in elderly users of the reference hospitals of the Mexican Institute of Social Insurance (IMSS by spanish initials) and Mexican Oils (PEMEX by spanish initials), from Villahermosa, Tabasco, Mexico, during 2009. MATERIALS AND METHODS: This is a cross-sectional study. The information was based on the registers of surgical interventions and institutional reports of the elderly inpatients who had a registered attention in their institution. Descriptive statistical analysis was performed considering the following variables: age, gender, hip fracture type, occurrence month, direct healthcare cost. RESULTS: Out of 10,765 records of hospitalized elderly, 57 hip fracture cases were found (33 in the IMSS and 24 in PEMEX). Hip fracture prevalence was 0.5%, (IMSS 1.1% and PEMEX 0.3%), being more frequent in women and older than 69. The most frequent fracture type was the femur neck one (78.9%). The estimated cost of healthcare in the hospital per patient was USD 5,803 in the IMSS and USD 11,800 in PEMEX. CONCLUSIONS: The hip fracture prevalence was higher in the IMSS users. Estimated healthcare costs per patient were higher than the reported in other institutions of the of the mexican health national system. PMID- 22086624 TI - [Identification of Leishmania species in patients and phlebotomines in transmission areas in a region of Peru]. AB - OBJECTIVES: To identify the species of Leishmania present in the skin lesions of patients and Lutzomyias living in endemic areas of La Libertad, Peru. MATERIALS AND METHODS: Molecular methods based on PCR and RFLP were used, which allowed to have efficient data with small amounts of samples (small specimens), due to their high sensitivity and ease of application in the field work. RESULTS: The results of PCR of clinical samples of patients and insect vectors showed the presence of Leishmania (V.) peruviana as a major causative agent of andean leishmaniasis transmitted by Lutzomyia peruensis. The presence of Leishmania (V.) guyanensis in Lutzomyia ayacuchensis, was found as well. CONCLUSIONS: The presence of L. (V.) peruviana and L. (V.) guyanensis in the Andean areas under study was found. These findings remark the need of a wider research about the geographical distribution of L. (V.) guyanensis and clinical features related to the infection in endemic areas of cutaneous leishmaniasis. PMID- 22086625 TI - [Western blot technique standardization of the diagnosis of human fasciolosis using Fasciola hepatica excreted-secreted antigens]. AB - OBJECTIVES: To evaluate the performance of the enzyme-linked immunoelectrotransfer blot assay (EITB, Western blot) using excretory/secretory antigens from adult forms of Fasciola hepatica (Fh E/S Ag) for the diagnosis of human fasciolosis. MATERIALS AND METHODS: Antigens were obtained after 18 hours of incubation in culture medium Minimum Essential Eagle, prepared at a protein concentration of 0.15 ug/uL and run against a pool of sera of patients with proven fasciolosis (confirmed by the finding of parasite eggs in the stool microscopy). Antigens of 10, 12, 17, 23, 27, 30, 36, 43, 66 and 136 kDa were detected and used to develop the Western blot technique. The sensitivity was evaluated using sera from 67 fasciolosis patients, and the specificity using sera from 57 patients with other parasitic diseases, and 10 from healthy individuals. RESULTS: Out of the 67 sera, 64 reacted with the 23 kDa band and 61 with the one of 17 kDa. These two bands were not detected in sera from patients with other parasitic diseases or in those from healthy volunteers and thus could be considered specific and diagnostic. CONCLUSIONS: The sensitivity of the test, using the bands of 17 and 23 kDa, was 95.5% for positive reactions to at least one of these two bands, being its specificity 100% with a positive predictive value of 100% and negative predictive value of 95.71%. PMID- 22086626 TI - [Internet addiction: development and validation of an instrument in adolescent scholars in Lima, Peru]. AB - OBJECTIVES: To develop and validate an instrument to assess Internet Addiction (IA) phenomenon in adolescents of Metropolitan Lima. MATERIALS AND METHODS: We performed an observational analytical study, including a sample of 248 high school adolescent students. In order to evaluate the IA, we constructed the questionnaire: "Scale for Internet Addiction of Lima" (SIAL), which assesses symptoms and dysfunctional characteristics. The resulting items were submitted to experts' judgment, finally obtaining a 11-item scale. RESULTS: The mean age was 14 years old. The psychometric analysis of the instrument showed a Cronbach' Alpha Coefficient of 0.84, with values of item-total correlation ranging from 0.45 to 0.59. The dimensional analysis yielded a two-dimensional structure that explained up to 50.7% of the total variance. The bi-dimensional data analysis revealed a significant association (p<0,001) between Dimension I (symptoms of IA) and the weekly time spent on the Internet, male sex, past history of bad behavior in school and plans for the future. Dimension II (dysfunction due to IA) had a significant association to past history of bad behavior, plans for the future (p<0,001) and missing school without valid reasons. CONCLUSIONS: The SIAL showed a good internal consistency, with moderate and significant inter-item correlations. The findings show that addiction has a dynamic role, which evidences a problem generated in family patterns and inadequate social networks. PMID- 22086627 TI - [Bibliometric analysis of scientific production about HIV/AIDS in Peru 1985 2010]. AB - OBJECTIVE: To analyze the evolution of published scientific articles on HIV/AIDS in Peru. METHODS: A bibliometric analysis of papers on HIV/AIDS published in journals indexed in MEDLINE, SciELO and LILACS until October 2010. We selected research papers fully developed in Peru, and multicenter studies with participating Peruvian sites. RESULTS: We identified 257 publications on HIV/AIDS, showing an increase since 2003. The average publication delay was 2.8+/ 1.8 years. Only 94 (36.6 %) articles were published in Spanish. The most studied areas were epidemiology (36.6 %) and clinical topics (35.8 %). The cross sectional design was the most frequent (56.8 %) followed by case series. According to the WHO classification, studies to learn more about the disease and risk factors predominated (85.6 %) and according to the intervention areas, 46.7 % focused on diagnosis and treatment. Most studies were conducted in Lima (65.9 %). 48.2 % of studies focused on people living with HIV/AIDS. Finally, Revista Peruana de Medicina Experimental y Salud Publica was the journal that published most articles on HIV/AIDS (9.7 %). CONCLUSIONS: We found a growth in scientific production on HIV/AIDS in Peru; however, we believe that the research undertaken was not based on an agreed national agenda or national research priorities, which might have limitted its dissemination and application. PMID- 22086628 TI - [Psychometric validation of the International Index of Erectile Function in patients with erectile dysfunction in Peru]. AB - OBJECTIVES: To perform the psychometric validation of the International Index of Erectile Function (IIEF) in patients with erectile dysfunction. MATERIALS AND METHODS: Prospective case series to evaluate the validity and the reliability of the scale. RESULTS: More than 90 % of experts considered that the IIEF questions evaluated the domains and the construct (content validity). There was a perfect concordance between the expert evaluation and the IIEF results (criteria validity, Kappa = 1). Significant differences were found in the score media by domains between patients with and without ED but when severity was evaluated, only differences in the erectile function domain were found (discriminatory validity). The Chronic Prostatitis Symptom Index (ISPC) and the IIEF showed divergent results (Kappa < 0.01, p = 0.44) in relation with the severity and the total scores showed no correlation (divergent validity) (r(s) = -0.22, p = 0.16). The correlation coefficients by domains were mild to moderate and the correlation between the total scores was high (rs = 0.8, p < 0.001) (test retest repeatability). A high degree of internal consistency with Cronbach's alpha values > 0.8 in the five domains was found. CONCLUSIONS: The cross-culturally validated IIEF in Peru is a valid and reliable instrument for its local use in the fields of clinics and research. PMID- 22086629 TI - [Maternal hemoglobin in Peru: regional differences and its association with adverse perinatal outcomes]. AB - OBJECTIVES: To evaluate hemoglobin (Hb) levels in pregnant women from different geographical regions from Peru; to establish anemia and erythrocytocis rates and to establish the role of Hb on adverse perinatal outcomes using the Perinatal Information System (PIS) database of Peruvian Ministry of Health. MATERIALS AND METHODS: Data were obtained from 379,816 births of 43 maternity care units between 2000 and 2010. Anemia and erythrocytocis rates were determined in each geographical region as well as rates of adverse perinatal outcomes. To analyze data the STATA program (version 10.0,Texas, USA) was used. The results were considered significant at p<0.01. RESULTS: Mild anemia rate was higher in the coast (25.8%) and low forest (26.2%). Moderate/severe anemia rate in low forest was 2.6% and at the coast was 1.0%. In the highland, the highest rate of moderate/severe anemia was in the southern highlands (0.6%). The highest rate of erythrocytocis was found in the central highland (23.7%), 11.9% in the southern highland and 9.5% in the north highland. Severe anemia and erythrocytocis were associated with adverse perinatal outcomes. CONCLUSIONS: There are differences by Peruvian geographical region in anemia rates. In the central highlands were found the highest rates of erythrocytocis due to hypoxia effect in the high altitudes; however in the southern highlands, erythrocytocis was lower. Severe anemia and erythrocytosis were associated with increased adverse perinatal outcomes. PMID- 22086630 TI - [Results of the implementation of three national guidelines for the prevention of HIV vertical transmission in Instituto Nacional Materno Perinatal. Lima, Peru]. AB - A retrospective analysis is performed in three successive periods between the years 1996 and 2009, in order to evaluate the impact of the implementation of three national guidelines for the prevention of the vertical transmission of HIV. 275 births were included in 13 years. Significant statistical differences were found in the percentage of HIV cases in the children exposed to the virus between the three periods: 15% during the period in which only zidovudine (AZT) was administered to the pregnant woman, 6.4% during the second period (administration of AZT to the pregnant woman not fulfilling HAART initiation criteria and HAART to those fulfilling criteria for this treatment), and 4% during the third period in which HAART was applied to all pregnant women with HIV infection. 95% of pregnant women ended their pregnancy by cesarean section and the 100% of children received infant formula. Changes made in national guidelines have produced a positive impact in the decrease of HIV infected children in the Instituto Nacional Materno Perinatal in Peru. PMID- 22086631 TI - [Cluster of multidrug-resistant tuberculosis cases in a school of the district of Ica, Peru]. AB - We describe the evolution and features of a cluster of Multidrug-resistant tuberculosis (MDR TB) cases that occurred in 2001, in a school located in a sub urban area of the district of Ica, Peru. We identified 15 students related before becoming infected with tuberculosis. The mean age of the cluster was 15 years. A total of 12 students were MDR-TB cases and 7 were drug-resistant to 5 first-line drugs (RHEZS). Five out of the 15 cases received at least 3 different anti tuberculosis treatment schemes. The average treatment duration was 37 months (minimum 21 and maximum 59 months). A total of 13 cases recovered and 2 died. This study describes a cluster of MDR -TB cases in an educational facility, which due to the epidemiological link and time presentation, is probably an outbreak of MDR TB with a satisfactory outcome after prolonged treatment. PMID- 22086632 TI - [Preliminary construction of a questionnaire about knowledge of HIV/AIDS in Colombian veterans]. AB - In order to identify the level of knowledge about HIV/AIDS in Colombia veterans of war in the year 2009, a questionnaire was designed, built and validated, using a mixed design, for which three stages were followed: 1) Bibliographic review and construction of items of the questionnaire using a focus group, 2) Evaluation of content validity by a pannel of experts, 3) APLICACION of the final questionnaire, we selected non-randomly 323 people who were part of group of veterans in Colombia, and 4) Validation of the questionnaire through the evaluation of internal consistency and principal component analysis. We found that the questionnaire explored three factors: forms of infection, inadequate beliefs, and HIV prevention, which accounted for 52% of the variance. The survey showed adequate internal consistency values (Cronbach's alpha = 0.77). These results suggest the use of the questionnaire to assess knowledge level related to the form of infection, inaccurate beliefs and prevention of HIV-AIDS in this population. PMID- 22086633 TI - [Sporotrichosis in patients attending a reference center in Abancay, Peru]. AB - A descriptive study was conducted between the months of May and August 2008 in Santa Teresa Medical Center, Abancay. Of 33 patients clinically suspected with Sporotrichosis: 20 patients were identified with Sporothrix schenckii. 11 (55%) of patients were males. Children between 0 and 14 years were most affected. 60% of the lesions were fixed cutaneous being more frequent in the head and neck (40%). 55% had lessions for less than one month. In pediatric population with involvement of head and neck, Sporotrichosis should be considered in the differential diagnosis of skin lesions of patients from endemic areas. PMID- 22086634 TI - [Seroprevalence of viral hepatitis B in university students in Abancay, Peru]. AB - To determine the prevalence of serological markers of viral hepatitis B in university students of the city of Abancay, we performed a cross-sectional study on 240 students from three universities, from January to October 2010. Informed consent was requested to every student, an epidemiological record was filled, and a venous blood sample was drawn to determine the presence of HBsAg, total anti - HBcAg, anti - HBe, HBeAg and IgM Anti - HBc by ELISA. A prevalence of 2.5% (six positive samples) was found for HBsAg and of 28.3% (68 positive samples) for anti - HbcAg antibodies. The male sex was associated with the presence of anti - HBcAg (OR = 2.0, 95% CI, 1.2 to 3.6). We did not found HBeAg or IgM anti - HBc, however, the 6 HBsAg carriers were anti - HBe positive. In conclusion hepatitis B infection is still a public health problem in Abancay, with a significant prevalence in university students. PMID- 22086635 TI - [Basic principles and methodological considerations of health economic evaluations]. AB - Health Economics is an essential instrument for health management, and economic evaluations can be considered as tools assisting the decision-making process for the allocation of resources in health. Currently, economic evaluations are increasingly being used worldwide, thus encouraging evidence-based decision making and seeking efficient and rational alternatives within the framework of health services activities. In this review, we present an overview and define the basic types of economic evaluations, with emphasis on complete Economic Evaluations (EE). In addition, we review key concepts regarding the perspectives from which EE can be conducted, the types of costs that can be considered, the time horizon, discounting, assessment of uncertainty and decision rules. Finally, we describe concepts about the extrapolation and spread of economic evaluations in health. PMID- 22086636 TI - [Synthesis studies as the basis for economic evaluations in health: the need for their quality appraisal]. AB - Synthesis studies (SS): systematic review and meta-analysis are the basis for developing Health Economic Evaluations (HEE). SS allow us to obtain parameters for estimating probabilities and effectiveness from the combination of the results of primary studies, and, as they include in their methodology the selection, evaluation, systematization and synthesis processes, they are considered the first level of hierarchy in scientific evidence. Nevertheless, they can be prone to bias and methodological failures that can affect the validity of their results. This article initially presents the relevance of the randomization in the hierarchic classification of research designs, then it reviews the main factors affecting the validity of the SS, emphasising the publication bias, the heterogeneity and the inclusion of primary studies with main objective differing from the one of the SS. Moreover, it presents individual studies like a valid alternative for the development of a SS. The conclusion is that one of the key aspects in a SS is the correct evaluation of the study types and the objective evaluation of their quality, being these primary or secondary. PMID- 22086637 TI - [Economic evaluations of health technologies: a global perspective for their implementation in Latin America]. AB - Phenomena as the progressive increase of health expenditure and the population aging have lead many countries to consider economic methodologies in order to obtain bigger sanitary benefits in contexts of limited resources. This article describes the basic components to consider in a health technology assessment , it analyses the process of decision making with cost-effectiveness analysis and reports how this methodology has been widely implemented in Latin America and the rest of the world. PMID- 22086638 TI - [Budgetary impact analysis in health: update with a model using a generic approach]. AB - Budgetary Impact Analysis (BIA) applied to health care can be defined as the estimate of the net financial costs that a given intervention would represent for a health care institution given the case it was covered. Routinely, BIAs are used to decide the inclusion or exclusion of drugs in therapeutic schemes; actually, the increased use of BIAs have raised awareness about the fact that health economic evaluations represent a partial view in the analysis of the consequences of incorporating health technologies. This paper seeks to identify the determinants and components of BIA, and to describe the development of a spreadsheet model that enables us to assess the Budget impact of any health technology and perform estimations with differing degrees of complexity. Its design explicitly adapts to the user skills and gaps in information, thus seeking to promote the development of these tools in the management fields in our countries. PMID- 22086639 TI - [Health technology assessment: experience in the Ministry of Health of Brazil]. AB - This article aims to describe the main activities carried out by the Ministry of Health of Brazil (MHB) for the development of Health Technology Assessments (HTA). It is a description based on the MHB efforts and strategies to strengthen this area in the last years. Five are the lines of action put in place for that purpose: (i) adoption of a National Policy for the Management of Health Technology, (ii) supporting the decision making process in the Unified Health System, (iii ) promotion of the performance of studies on HTA, (iv) training of strategic human resources, and (v) institutional coordination at national and international levels. However, challenges remain to achieve a more effective structure for HTA in Brazil, like the creation of a government institution with greater administrative flexibility, among others. PMID- 22086640 TI - [Chromomycosis: report of a disabling case]. AB - Chromomycosis is a deep subcutaneous mycosis caused by different dymorphic fungi species that normally live in vegetal debris. We report the case of a 51 year-old patient that six years previous to the evaluation worked making roof tiles in Madre de Dios, Peru; where he presented an initial papular lesion in a leg, which continued expanding until the 4 limbs were affected with disabling verrucous lesions. Fumagoid cells were found in the skin biopsy. The patient was hospitalized and received topical cleaning, antibiotics and terbinafine. He was discharged two months later with clinical improvement. PMID- 22086641 TI - [Cayetano Heredia (1797-1861)]. PMID- 22086642 TI - [Tegumentary leishmaniosis, a look at a neglected tropical disease]. PMID- 22086643 TI - [Estimation of chronic co-morbidity on health costs in elderly patients with neurological disorders]. PMID- 22086644 TI - [Etiologic confirmation of the first two cases of human hantavirosis in Peru]. PMID- 22086645 TI - [Challenges to new regulations of pharmaceutical products in Peru]. PMID- 22086646 TI - [Health situation in Peru: the pending agenda]. PMID- 22086647 TI - Ubiquitous expression of selenoprotein N transcripts in chicken tissues and early developmental expression pattern in skeletal muscles. AB - Previous results revealed a ubiquitous expression pattern of selenoprotein N (SelN, SEPN1) in humans, zebrafish, and mouse, suggesting that it plays a potential role during the embryogenesis of these species. However, no information is known about the tissue distribution of SelN and mRNA expression analysis in the muscle tissues during development in birds. We analyzed the mRNA expression of SelN in 26 different tissues of 90-day-old chickens and the expression of SelN in the muscle tissues of 12-day-old chicken embryos and 15-month-old adult chickens by quantitative real-time PCR. The results showed that SelN transcripts were expressed widely in the chicken tissues. Moreover, the expression of SelN mRNA in skeletal muscles was present at a high level in whole embryos and at a lower level in postnatal stages. However, the expression of SelN mRNA in cardiac muscle showed a different expression pattern compared with skeletal muscles. Our data indicate that the expression of the SelN gene in chicken is ubiquitous, suggesting a role of SelN in the development of chick embryo skeletal muscles. PMID- 22086648 TI - The relationship between parental knowledge and monitoring and child and adolescent conduct problems: a 10-year update. AB - Inadequate parental monitoring is widely recognized as a risk factor for the development of child and adolescent conduct problems. However, previous studies examining parental monitoring have largely measured parental knowledge and not the active methods used by parents to track the activities and behavior of their children. The seminal work of Stattin and Kerr (Child Dev 71:1072-1085, 2000; Kerr and Stattin in Dev Psychol 36:366-380, 2000) has challenged the field to reinterpret the construct of parental monitoring, focusing on the active components of this parenting behavior. As a result, this area of research has witnessed a resurgence of activity. The goal of the current paper is to review the evidence regarding the relationship between parental knowledge and monitoring and child and adolescent conduct problems that has accumulated during the past decade. Forty-seven studies published between 2000 and 2010 were identified by searching major databases and bibliographies and were included in this review. This paper will examine the following areas: (a) "parental monitoring" as "parental knowledge"; (b) parental knowledge as driven by child disclosure; (c) the relationship between parental knowledge and monitoring and child and adolescent conduct problems; (d) bidirectional associations between parental knowledge and monitoring and child and adolescent conduct problems; (e) contextual influences on parental knowledge and monitoring; (f) antecedents of parental knowledge and monitoring; (g) clinical implications of research on parental knowledge and monitoring; and (h) limitations of existing research and future directions. PMID- 22086649 TI - Readers' use of source information in text comprehension. AB - In two experiments, we examined the role of discrepancy on readers' text processing of and memory for the sources of brief news reports. Each story included two assertions that were attributed to different sources. We manipulated whether the second assertion was either discrepant or consistent with the first assertion. On the basis of the discrepancy-induced source comprehension (D-ISC) assumption, we predicted that discrepant stories would promote deeper processing and better memory for the sources conveying the messages, as compared to consistent stories. As predicted, readers mentioned more sources in summaries of discrepant stories, recalled more sources, made more fixations, and displayed longer gaze times in source areas when reading discrepant than when reading consistent stories. In Experiment 2, we found enhanced memory for source-content links for discrepant stories even when intersentential connectors were absent, and regardless of the reading goals. Discussion was focused on discrepancies as one mechanism by which readers are prompted to encode source-content links more deeply, as a method of integrating disparate pieces of information into a coherent mental representation of a text. PMID- 22086650 TI - Bilingual recognition memory: stronger performance but weaker levels-of processing effects in the less fluent language. AB - The effects of bilingual proficiency on recognition memory were examined in an experiment with Spanish-English bilinguals. Participants learned lists of words in English and Spanish under shallow- and deep-encoding conditions. Overall, hit rates were higher, discrimination greater, and response times shorter in the nondominant language, consistent with effects previously observed for lower frequency words. Levels-of-processing effects in hit rates, discrimination, and response time were stronger in the dominant language. Specifically, with shallow encoding, the advantage for the nondominant language was larger than with deep encoding. The results support the idea that memory performance in the nondominant language is impacted by both the greater demand for cognitive resources and the lower familiarity of the words. PMID- 22086651 TI - Correlation between psychological distress and C-reactive protein : Comment on Puustinen et al., "Psychological distress and C-reactive protein: do health behaviours and pathophysiological factors modify the association?" (Eur Arch Psychiatry Clin Neurosci 2011;261:277-84). PMID- 22086653 TI - The Journal of Computer-Aided Molecular Design: a bibliometric note. AB - Summarizes the articles in, and the citations to, volumes 2-24 of the Journal of Computer-Aided Molecular Design. The citations to the journal come from almost 2000 different sources that span a very wide range of academic subjects, with the most heavily cited articles being descriptions of software systems and of computational methods. PMID- 22086652 TI - Computational and experimental studies of the interaction between phospho peptides and the C-terminal domain of BRCA1. AB - The C-terminal domain of BRCA1(BRCT) is involved in the DNA repair pathway by recognizing the pSXXF motif in interacting proteins. It has been reported that short peptides containing this motif bind to BRCA1(BRCT) in the micromolar range with high specificity. In this work, the binding of pSXXF peptides has been studied computationally and experimentally in order to characterize their interaction with BRCA1(BRCT). Elucidation of the contacts that drive the protein ligand interaction is critical for the development of high affinity small molecule BRCA1 inhibitors. Molecular dynamics (MD) simulations revealed the key role of threonine at the peptide P+2 position in providing structural rigidity to the ligand in the bound state. The mutation at P+1 had minor effects. Peptide extension at the N-terminal position with the naphthyl amino acid exhibited a modest increase in binding affinity, what could be explained by the dispersion interaction of the naphthyl side-chain with a hydrophobic patch. Three in silico end-point methods were considered for the calculation of binding free energy. The Molecular Mechanics Poisson-Boltzmann Surface Area and the Solvated Interaction Energy methods gave reasonable agreement with experimental data, exhibiting a Pearlman predictive index of 0.71 and 0.78, respectively. The MM-quantum mechanics-surface area method yielded improved results, which was characterized by a Pearlman index of 0.78. The correlation coefficients were 0.59, 0.61 and 0.69, respectively. The ability to apply a QM level of theory within an end-point binding free energy protocol may provide a way for a consistent improvement of accuracy in computer-aided drug design. PMID- 22086654 TI - Comparative analyses of overall survival in patients with anaplastic lymphoma kinase-positive and matched wild-type advanced nonsmall cell lung cancer. AB - BACKGROUND: The purpose of this study was to investigate the overall survival (OS) of patients with advanced ALK-positive nonsmall cell lung cancer (NSCLC) who were managed in the pre-ALK inhibitor era and to compare their survival with that of a matched case cohort of ALK wild-type (WT) patients. METHODS: Data from 1166 patients who had stage IIIB/IV NSCLC with nonsquamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. ALK fluorescence in situ hybridization (FISH) was used to analyze 262 patients who either had the WT epidermal growth factor receptor (EGFR) or were nonresponders to previous EGFR tyrosine kinase inhibitor (TKI) therapy. Overall survival (OS) was compared between 3 groups: 1) ALK-positive patients, 2) EGFR mutation-positive patients, and 3) ALK-WT/EGFR-WT patients. Progression-free survival (PFS) after first-line chemotherapy and EGFR TKIs also was analyzed. RESULTS: Twenty-three patients were ALK-positive according to FISH analysis and did not receive ALK inhibitors during follow-up. The median OS for ALK-positive patients, EGFR mutation-positive patients, and WT/WT patients was 12.2 months, 29.6 months, and 19.3 months, respectively (vs EGFR mutation-positive patients, P = .001; vs WT/WT, P = .127). The PFS after first-line chemotherapy for the 3 groups was not different. However, the PFS for patients who received EGFR TKIs was shorter in ALK-positive patients compared with the other 2 groups (vs EGFR mutation-positive patients, P < .001; vs WT/WT, P < .021). CONCLUSIONS: In the pre-ALK inhibitor era, ALK-positive patients experienced the shortest survival, although it did not differ statistically from that of WT/WT patients. Although their responses to platinum-based chemotherapy were not different from comparator groups, ALK-positive patients were even more resistant to EGFR TKI treatment than WT/WT patients. PMID- 22086656 TI - Intein-mediated construction of a library of fluorescent Rab GTPase probes. AB - Rab GTPases play a key role in the regulation of membrane trafficking. Post translational geranylgeranylation is critical for their biological activity and is conferred by Rab geranylgeranyl transferease (RabGGTase), together with an accessory factor, Rab escort protein (REP). Mechanistic studies of Rab prenylation and identification of RabGGTase inhibitors require sensitive reporters of Rab prenylation. In the present work, a combination of protein engineering and expressed protein ligation was used to construct a library of semisynthetic Rab7 fluorescent conjugates. In order to avoid synthesis of a large number of fluorescently labeled peptides, we developed a strategy that combined thiol-reactive dye-labeling of cysteine with in vitro protein ligation. Application of this strategy required optimization of labeling and ligation conditions to promote thiol labeling and disfavor intramolecular cyclization. Using this approach, we constructed 46 fluorescent sensors with different spectral properties that reported on the interaction of Rab7 with RabGGTase, REP 1, and the overall prenylation reaction. Two constructs, Rab7Delta3CCK(NBD) and Rab7Delta2SCCC-dans, displayed 2.5- and 1.5-fold increase in fluorescence, respectively, upon prenylation. Moreover, dansyl-, NBD (4-nitro-benzofurazan)-, I BA-, and I-SO-labeled Rab7 conjugates exhibited two- to tenfold change in fluorescence upon binding to REP or RabGGTase. These fluorescent sensors allowed us to monitor Rab prenylation in real time and to investigate the assembly of Rab REP binary and Rab-REP-RabGGTase ternary complexes. PMID- 22086655 TI - BK virus infection in human immunodeficiency virus-infected patients. AB - The aim of this study is to evaluate the prevalence of BK virus (BKV) infection in HIV-positive patients receiving highly active antiretroviral therapy (HAART) in our hospital. The presence of BKV was analysed in urine and plasma samples from 78 non-selected HIV-infected patients. Clinical data were recorded using a pre-established protocol. We used a nested PCR to amplify a specific region of the BKV T-large antigen. Positive samples were quantified using real-time PCR. Mean CD4 count in HIV-infected patients was 472 cells/mm3 and median HIV viral load was <50 copies/mL. BKV viraemia was detected in only 1 HIV-positive patient, but 57.7% (45 out of 78) had BKV viruria, which was more common in patients with CD4 counts>500 cells/mm3 (74.3% vs 25.7%; p=0.007). Viruria was present in 21.7% of healthy controls (5 out of 23 samples, p=0.02). All viral loads were low (<100 copies/mL), and we could not find any association between BKV infection and renal or neurological manifestations. We provide an update on the prevalence of BKV in HIV-infected patients treated with HAART. BKV viruria was more common in HIV infected patients; however, no role for BKV has been demonstrated in this population. PMID- 22086657 TI - Facet-mediated photodegradation of organic dye over hematite architectures by visible light. PMID- 22086658 TI - Pemetrexed induces both intrinsic and extrinsic apoptosis through ataxia telangiectasia mutated/p53-dependent and -independent signaling pathways. AB - Pemetrexed, a new-generation antifolate, has demonstrated promising single-agent activity in front- and second-line treatments of non-small cell lung cancer. However, the molecular mechanism of pemetrexed-mediated antitumor activity remains unclear. The current study shows that pemetrexed induced DNA damage and caspase-2, -3, -8, and -9 activation in A549 cells and that treatment with caspase inhibitors significantly abolished cell death, suggesting a caspase dependent apoptotic mechanism. The molecular events of pemetrexed-mediated apoptosis was associated with the activation of ataxia telangiectasia mutated (ATM)/p53-dependent and -independent signaling pathways, which promoted intrinsic and extrinsic apoptosis by upregulating Bax, PUMA, Fas, DR4, and DR5 and activating the caspase signaling cascade. Supplementation with dTTP allowed normal S-phase progression and rescued apoptotic death in response to pemetrexed. Overall, our findings reveal that the decrease of thymidylate synthase and the increase of Bax, PUMA, Fas, DR4, and DR5 genes may serve as biomarkers for predicting responsiveness to pemetrexed. PMID- 22086659 TI - Blood pressure and TNF-alpha act synergistically to increase leucocyte CD11b adhesion molecule expression in the BELFAST study: implications for better blood pressure control in ageing. AB - Hypertension, a key risk factor for stroke, cardiovascular disease and dementia, is associated with chronic vascular inflammation, and although poorly understood, putative mechanisms include pro-inflammatory responses induced by mechanical stretching, with cytokine release and associated up-regulated expression of adhesion molecules. Because blood pressure increases with age, we measured baseline and tumour necrosis alpha (TNF-alpha)-stimulated CD11b/CD18 adhesion molecule expression on leucocytes to assess any association between the two. In 38 subjects (mean age 85 years), consecutively enrolled from Belfast Elderly Longitudinal Free-Living Aging Study (BELFAST), baseline and TNF-alpha-stimulated CD11b/CD18 expression on separated monocytes and neutrophils increased with systolic blood pressure >120 mmHg (p = 0.05) and for lymphocytes, with diastolic blood pressure >80 mmHg (p < 0.05).These findings show increased potential stickiness of intravascular cells with increasing blood pressure which is accentuated by TNF-alpha, and suggest mechanistic reasons why better hypertension control is important. PMID- 22086660 TI - Changes in depressive symptoms, social support, and loneliness over 1 year after a minimum 3-month videoconference program for older nursing home residents. AB - BACKGROUND: A 3-month videoconference interaction program with family members has been shown to decrease depression and loneliness in nursing home residents. However, little is known about the long-term effects on residents' depressive symptoms, social support, and loneliness. OBJECTIVE: The purpose of this longitudinal quasi-experimental study was to evaluate the long-term effectiveness of a videoconference intervention in improving nursing home residents' social support, loneliness, and depressive status over 1 year. METHODS: We purposively sampled 16 nursing homes in various areas of Taiwan. Elderly residents (N = 90) of these nursing homes meeting our inclusion criteria were divided into an experimental (n = 40) and a comparison (n = 50) group. The experimental group received at least 5 minutes/week for 3 months of videoconference interaction with their family members in addition to usual family visits, and the comparison group received regular family visits only. Data were collected in face-to face interviews on social support, loneliness, and depressive status using the Social Support Behaviors Scale, University of California Los Angeles Loneliness Scale, and Geriatric Depression Scale, respectively, at four times (baseline, 3 months, 6 months, and 12 months after baseline). Data were analyzed using the generalized estimating equation approach. RESULTS: After the videoconferencing program, participants in the experimental group had significantly lower mean change in instrumental social support scores at 6 months (-0.42, P = .03) and 12 months ( 0.41, P = .03), and higher mean change in emotional social support at 3 (0.74, P < .001) and 12 months (0.61, P = .02), and in appraisal support at 3 months (0.74, P = .001) after adjusting for confounding variables. Participants in the experimental group also had significantly lower mean loneliness and depressive status scores at 3 months (-5.40, P < .001; -2.64, P < .001, respectively), 6 months (-6.47, P < .001; -4.33, P < .001), and 12 months (-6.27, P = .001; -4.40, P < .001) compared with baseline than those in the comparison group. CONCLUSION: Our videoconference program had a long-term effect in alleviating depressive symptoms and loneliness for elderly residents in nursing homes. This intervention also improved long-term emotional social support and short-term appraisal support, and decreased residents' instrumental social support. However, this intervention had no effect on informational social support. PMID- 22086661 TI - Improved chemical energy component analysis. AB - An improved SCF energy decomposition scheme is proposed in which a special treatment is introduced for those "ionic" one-center electron-electron repulsion energy contributions which arise from the use of doubly filled bonding orbitals. These terms characterize the bonding pattern rather than the state of the atoms, therefore they are attributed to the bonds and are redistributed between them in accord with the bond orders. This permits one to solve the dilemma which we had with the previous decomposition schemes, and obtain very "chemical" one- and two center energy components, characterizing well the bonding situation in different molecules. PMID- 22086662 TI - Prognostic value of tumour necrosis and host inflammatory responses in colorectal cancer. AB - BACKGROUND: Tumour necrosis is a marker of poor prognosis in some tumours but the mechanism is unclear. This study examined the prognostic value of tumour necrosis and host inflammatory responses in colorectal cancer. METHODS: This was a retrospective study of patients undergoing potentially curative resection of colorectal cancer at a single surgical institution over a 10-year period. Patients who underwent preoperative radiotherapy were excluded. The systemic and local inflammatory responses were assessed using the modified Glasgow Prognostic Score and Klintrup-Makinen criteria respectively. Original tumour sections were retrieved and necrosis graded as absent, focal, moderate or extensive. Associations between necrosis and clinicopathological variables were examined, and multivariable survival analyses carried out. RESULTS: A total of 343 patients were included between 1997 and 2007. Tumour necrosis was graded as absent in 32 (9.3 per cent), focal in 166 (48.4 per cent), moderate in 101 (29.4 per cent) and extensive in 44 (12.8 per cent). There were significant associations between tumour necrosis and anaemia (P = 0.022), white cell count (P = 0.006), systemic inflammatory response (P < 0.001), local inflammatory cell infiltrate (P = 0.004), tumour node metastasis (TNM) stage (P = 0.015) and Petersen Index (P = 0.003). On univariable survival analysis, tumour necrosis was associated with cancer-specific survival (P < 0.001). On multivariable survival analysis, age (hazard ratio (HR) 1.29, 95 per cent confidence interval 1.00 to 1.66), systemic inflammatory response (HR 1.74, 1.27 to 2.39), low-grade local inflammatory cell infiltrate (HR 2.65, 1.52 to 4.63), TNM stage (HR 1.55, 1.02 to 2.35) and high risk Petersen Index (HR 3.50, 2.21 to 5.55) were associated with reduced cancer specific survival. CONCLUSION: The impact of tumour necrosis on colorectal cancer survival may be due to close associations with the host systemic and local inflammatory responses. PMID- 22086663 TI - Square planar coordinate iron oxides. AB - We will provide an overview of the synthesis, structures, chemical and physical properties of novel iron oxides bearing FeO(4) square planar coordination, such as SrFeO(2) and Sr(3)Fe(2)O(5). The preparation of these materials relies on topotactic low-temperature reduction using metal hydrides. For instance, a simple 3D perovskite structure SrFeO(3) converts to a 2D structure SrFeO(2)via SrFeO(2.5). SrFeO(2) shows a remarkable stability against temperature and chemical substitution (for both A- and B-sites) and also tolerates distortions of square planes toward tetrahedra to adapt different A sites. Such structural stability and flexibility arise from strong covalent interactions not only through the in-plane Fe-O-Fe superexchange interactions but also through the out of-plane Fe-Fe direct exchange interactions, and explains why SrFeO(2) exhibits magnetic order far beyond room temperature. The application of pressure on SrFeO(2) and Sr(3)Fe(2)O(5) further enhances the Fe-Fe direct exchange interactions and eventually induces striking transitions at around 34 GPa: spin state transition from S = 2 to S = 1, insulator-to-metal transition, and antiferro-to-ferromagnetic transition. The high mobility of oxide ions at relatively low temperatures, during the reduction and reoxidation reaction process would offer an important challenge to tailor and design new solid oxide fuel cells/membranes toward lowering working temperatures. PMID- 22086664 TI - Voluntary consent in correctional settings: do offenders feel coerced to participate in research? AB - A major ethical concern in research with criminal offenders is the potential for abuse due to coercive influences that may adversely affect offenders' capacity to give voluntary consent to participate in research conducted in correctional settings. Despite this concern, to date there have been almost no systematic scientific investigations of the extent to which offenders themselves perceive that coercion occurs in these settings or that it is likely to influence their decisions about research participation. In a sample of over 600 ethnically diverse men and women recruited from various prisons and community corrections facilities in Texas and Florida, we used a vignette-based survey concerning a hypothetical research project to measure and compare offenders' global perceptions of coercive processes, as well as the differential salience and perceived coercive influence of specific factors (e.g., coercion by other inmates, inducements from staff). Somewhat surprisingly, across multiple outcome measures our participants on average reported relatively little in the way of significant coercive influences on their capacity to make voluntary decisions concerning research participation. Implications and directions for future research on coercive influences in offender research are discussed. PMID- 22086665 TI - Medication-assisted treatment research with criminal justice populations: challenges of implementation. AB - Creating, implementing and evaluating substance abuse interventions, especially medication-assisted treatments, for prisoners, parolees, and probationers with histories of heroin addiction is an especially challenging endeavor because of the difficulty in coordinating and achieving cooperation among diverse criminal justice, substance abuse treatment, research, and social service agencies, each with its own priorities and agenda. In addition, there are special rules that must be followed when conducting research with criminal justice-involved populations, particularly prisoners. The following case studies will explore the authors' experience of over 10 years conducting pharmacotherapy research using methadone, buprenorphine, and naltrexone with criminal justice populations. The major obstacles and how they were overcome are presented. Finally, recommendations are provided with regard to implementing and conducting research with criminal justice populations. PMID- 22086666 TI - Prevention of recurrent herpes labialis outbreaks through low-intensity laser therapy: a clinical protocol with 3-year follow-up. PMID- 22086667 TI - Fatal course of an autochthonous hepatitis E virus infection in a patient with leukemia in Germany. AB - An acute infection with hepatitis E virus (HEV) genotype 3 subtype c was diagnosed in a patient with chronic lymphatic B-cell leukemia 6 weeks after the infusion of donor lymphocytes. Despite intensive care the patient died 39 days after admission due to pericardial effusion that was related to acute liver failure. We suggest that diagnostic procedures for detection of HEV infection should be seriously considered for the immunocompromised patient with elevated liver enzymes in the absence of a travel history to HEV endemic countries. PMID- 22086668 TI - Gambling and problem gambling among young adolescents in Great Britain. AB - International evidence suggests that problem gambling tends to be 2-4 times higher among adolescents as among adults and this proves to be true of Great Britain according to the latest adolescent prevalence survey. 8,958 British children (11-15) were surveyed in 201 schools during late 2008 and 2009. The questionnaire included a standard screen, DSM-IV-MR-J, to test for problem gambling. Our regression models explore influences of demographic, home and school characteristics on probabilities (both unconditional and conditional on being a gambler) of a child testing positive for problem gambling. More than 20% of children participated in gambling and, of these, nearly 8% tested positive. Age-group prevalence of problem gambling was 1.9%, compared with 0.6-0.9% in the most recent official adult surveys. Boys were much more likely than girls to gamble and to exhibit symptoms of problem gambling if they did. Generally, home characteristics, particularly parental attitude and example, dominated school characteristics in accounting for risks. Unanticipated findings included significantly elevated probabilities of problem gambling among Asian children and among children who live in a home without siblings. Child income was also a potent predictor of gambling and problem gambling. PMID- 22086669 TI - Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16 positive oropharyngeal carcinoma. AB - BACKGROUND: Extracapsular spread (ECS) is commonly used to justify adjuvant chemotherapy in patients with head and neck cancer. The role of ECS as a prognosticator and adjuvant therapy determinant in surgically resected, human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC), however, has never been determined. METHODS: Of 210 oropharynx patients in a prospective transoral laser microsurgery database, 152 patients who had p16-positive primary OPSCC and pathologically positive necks were eligible for the study. ECS was measured from routine reporting (ECS(report)) and by using a novel histologic grading system (ECS(graded)). Proportional hazards models and matched analyses were used to compare the impact of ECS and adjuvant therapy on disease-free survival (DFS). Patients with and without graded ECS were matched for T-stage, surgical margins, and adjuvant therapy. RESULTS: At a median follow-up of 43 months, the presence of ECS was not associated with poorer DFS in multivariate analyses (ECS(report): hazard ratio [HR], 3.42; 95% confidence interval [CI], 0.45-25.88; P = .23; ECS(graded): HR, 2.54; 95% CI, 0.88-7.34; P = .09). T-stage and high-grade ECS, ie soft tissue metastasis (STM(graded)) were prognostic. Overall and in the presence of ECS or even STM, adjuvant CRT was not associated with better DFS over radiotherapy alone (HR, 0.25; 95% CI, 0.06-1.13; P = .07). In addition, matched analyses demonstrated no significant reduction in DFS for the presence of ECS versus the absence of ECS or reduced DFS for the administration of adjuvant radiotherapy alone versus CRT in ECS-positive patients. CONCLUSIONS: Routinely reported ECS was not prognostic in this study. Adjuvant CRT versus radiotherapy alone produced no improvement in DFS for ECS positive patients. The authors propose that de-escalated adjuvant therapy should be considered for patients with p16-positive OPSCC who undergo surgery and that routinely reported ECS should not be used to justify adjuvant chemotherapy. PMID- 22086670 TI - Generalized linear model for partially ordered data. AB - Within the rich literature on generalized linear models, substantial efforts have been devoted to models for categorical responses that are either completely ordered or completely unordered. Few studies have focused on the analysis of partially ordered outcomes, which arise in practically every area of study, including medicine, the social sciences, and education. To fill this gap, we propose a new class of generalized linear models--the partitioned conditional model--that includes models for both ordinal and unordered categorical data as special cases. We discuss the specification of the partitioned conditional model and its estimation. We use an application of the method to a sample of the National Longitudinal Study of Youth to illustrate how the new method is able to extract from partially ordered data useful information about smoking youths that is not possible using traditional methods. PMID- 22086671 TI - Epoxyquinone formation catalyzed by a two-component flavin-dependent monooxygenase involved in biosynthesis of the antibiotic actinorhodin. AB - The biosynthetic gene cluster of the aromatic polyketide antibiotic actinorhodin (ACT) in Streptomyces coelicolor A3(2) carries a pair of genes, actVA-ORF5 and actVB, that encode a two-component flavin-dependent monooxygenase (FMO). Our previous studies have demonstrated that the ActVA-ORF5/ActVB system functions as a quinone-forming C-6 oxygenase in ACT biosynthesis. Furthermore, we found that this enzyme system exhibits an additional oxygenation activity with dihydrokalafungin (DHK), a proposed intermediate in the ACT biosynthetic pathway, and generates two reaction products. These compounds were revealed to be monooxygenated derivatives of kalafungin, which is spontaneously formed through oxidative lactonization of DHK. Their absolute structures were elucidated from their NMR spectroscopic data and by computer modeling and X-ray crystallography as (5S,14R)-epoxykalafungin and (5R,14S)-epoxykalafungin, demonstrating an additional epoxyquinone-forming activity of the ActVA-ORF5/ActVB system in vitro. PMID- 22086672 TI - Quantitative determination of four compounds and fingerprint analysis in the rhizomes of Drynaria fortunei (Kunze) J. Sm. AB - A rapid, sensitive, and accurate reversed-phase high-performance liquid chromatography with photodiode array detection method was developed for both quantitative determination of four compounds (caffeic acid-4-O-beta-D glucopyranoside, 5,7-dihydroxychromone-7-O-rutinoside, neoeriocitrin and naringin) and fingerprint analysis of the rhizomes of Drynaria fortunei (Kunze) J. Sm. The chromatographic separation was accomplished on an MZ-C18 column (4.6 * 250 mm, 5 MUm) using gradient elution with acetonitrile and 0.02% aqueous acetic acid, at a flow rate of 1.0 mL min(-1), an operating temperature of 25 degrees C, and a wavelength of 260 nm. The four compounds showed good regression relationship (R (2) > 0.9990) within linear ranges, and their recoveries were in the range of 98.11-102.23%. In the chromatographic fingerprint, thirteen common peaks were found and selected as characteristic peaks to assess the consistency of ten batches of the rhizomes of D. fortunei. The results indicate that the method of multiple compounds determination in combination with chromatographic fingerprint analysis is suitable for systematic quality evaluation of D. fortunei. PMID- 22086673 TI - Anti-inflammatory and anti-nociceptive effects of the ethanolic extracts of Alkanna frigida and Alkanna orientalis. AB - Alkanna species are used in Iranian traditional medicine for treatment of rheumatoid arthritis and other inflammatory diseases. This study was designed to evaluate the anti-inflammatory and anti-nociceptive effects of Alkanna frigida and Alkanna orientalis ethanolic extracts via the carrageenan-induced paw edema test and formalin test in rat and mouse, respectively. Ethanolic extracts of plant root were prepared and were injected intraperitoneally 60 min before carrageenan-induced inflammation or formalin-induced nociception at 100, 200 and 400 mg/kg. Anti-inflammatory effects of plants were monitored for 3 h after carrageenan injection and anti-nociceptive effects were evaluated during the first hour after formalin injection. Diclofenac, a well-known anti-inflammatory and anti-nociceptive agent, was used as a positive control. Our results show that, in contrast to Alkanna orientalis, ethanolic extract of Alkanna frigida significantly decreases carrageenan-induced inflammation at 400 mg/kg, especially 3 h after inflammation induction. Both Alkanna frigida and Alkanna orientalis ethanolic extracts possess a remarkable anti-nociceptive effect at each dose (100, 200 and 400 mg/kg) in a dose-dependent manner during the first hour after formalin injection.The present findings provide more evidence for the potential anti-nociceptive effect of Alkanna sp. and the anti-inflammatory effect of Alkanna frigida. It supports their traditional indication in the treatment of pain and inflammatory-related diseases. These useful effects may result from the inhibitory interaction of the plant ethanolic extract with cyclooxygenase-2 enzyme and the subsequent reduction in prostaglandin production. PMID- 22086674 TI - Withania somnifera extract attenuates stem cell factor-stimulated pigmentation in human epidermal equivalents through interruption of ERK phosphorylation within melanocytes. AB - We previously demonstrated that mitogen-activated protein kinase (MAPK) signaling, including microphthalmia-associated transcription factor (MITF) and cAMP response element-binding protein (CREB) phosphorylation, is a major pathway involved in up-regulating melanogenesis within human melanocytes in several hyperpigmentary disorders such as UVB melanosis and lentigo senilis. Recently, a redox imbalance was shown to be closely linked to a variety of altered cellular responses in which the precise balance between levels of oxidizing and reducing equivalents that reflect the intracellular redox condition profoundly affects intracellular signaling pathways, especially the MAPK pathway. To elucidate the effects of redox balance regulation on epidermal pigmentation, we used an antioxidant-rich extract of the herb Withania somnifera to assess its effect on stem cell factor (SCF)-stimulated pigmentation in human epidermal equivalents and analyzed its biological mechanism of action. Addition of the W. somnifera extract (WSE) caused a marked reduction in SCF-stimulated pigmentation in a dose dependent manner after 14 days of treatment, which was accompanied by a significant decrease in eumelanin content. In WSE-treated human epidermal equivalents, melanocyte-specific proteins (including tyrosinase) were significantly suppressed at the gene and protein levels by WSE. Signaling analysis with immunoblots revealed that in human melanocytes or human melanoma cells treated with WSE, there was a marked deficiency in SCF-stimulated phosphorylation of ERK, MITF and CREB, but not of Raf-1 and MEK. Since WSE had no direct inhibitory effect on tyrosinase activity and no melano-cytotoxic effect on melanocytes present in the human epidermal equivalents or on cultured human melanocytes, the sum of these findings indicates that WSE attenuates SCF stimulated pigmentation by preferentially interrupting ERK phosphorylation within melanocytes and can serve as a therapeutic tool for SCF-associated hyperpigmentary disorders. PMID- 22086675 TI - Effect of silibinin in human colorectal cancer cells: targeting the activation of NF-kappaB signaling. AB - Chronic inflammation is one of the primary causes of colorectal cancer (CRC), and major inflammatory pathways implicated in CRC are cyclooxygenase-2 (COX-2) and iNOS; both regulated by nuclear factor-kappa B (NF-kappaB) suggesting that inhibitors of these pathways could be ideal against CRC. Silibinin has shown promising efficacy against various malignancies including CRC, and therefore here we assessed whether silibinin targets NF-kappaB activation and associated signaling as a mechanism of its anti-inflammatory and anti-cancer effects in CRC. Our results indicated that silibinin treatment (50-200 uM) of human CRC SW480, LoVo, and HT29 cells strongly inhibits tumor necrosis factor alpha-induced NF kappaB activation together with decreased nuclear levels of both p65 and p50 sub units. Silibinin also significantly increased IkappaBalpha level with a concomitant decrease in phospho-IkappaBalpha, without any effect on TNFR1, TRADD, and RIP2, indicating its inhibitory effect on IkappaB kinase alpha activity. Next we assessed the effect of oral silibinin feeding on NF-kappaB pathway in SW480 (COX-2 negative) and LoVo (COX-2 positive) tumor xenografts in nude mice. Together with its inhibitory efficacy on tumor growth and progression, silibinin inhibited NF-kappaB activation in both xenografts. The protein levels of various NF-kappaB-regulated molecules such as Bcl-2, COX-2, iNOS, VEGF, and MMPs were also decreased by silibinin in both cell culture studies and xenograft analyses, suggesting its potential to alter NF-kappaB transcriptional activity. Together, these findings are highly significant in establishing for the first time that silibinin suppresses CRC growth and progression possibly through its anti inflammatory activity by interfering with NF-kappaB activation and thus has potential against human CRC. PMID- 22086676 TI - Magnetochiral effects in amphiphilic porphyrin J-aggregates. AB - The detection of magnetochiral dichroism (MChD; CD: circular dichroism) in a suspension of J-aggregate particles of an achiral amphiphilic nonmetalated porphyrin renews the interest for porphyrins in supramolecular chemistry and reinforces the concept that novel advanced materials can be obtained through self assembly and auto-organization processes (see picture). PMID- 22086677 TI - Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. AB - Nanomaterials hold promise as multifunctional diagnostic and therapeutic agents. However, the effective application of nanomaterials is hampered by limited understanding and control over their interactions with complex biological systems. When a nanomaterial enters a physiological environment, it rapidly adsorbs proteins forming what is known as the protein 'corona'. The protein corona alters the size and interfacial composition of a nanomaterial, giving it a biological identity that is distinct from its synthetic identity. The biological identity determines the physiological response including signalling, kinetics, transport, accumulation, and toxicity. The structure and composition of the protein corona depends on the synthetic identity of the nanomaterial (size, shape, and composition), the nature of the physiological environment (blood, interstitial fluid, cell cytoplasm, etc.), and the duration of exposure. In this critical review, we discuss the formation of the protein corona, its structure and composition, and its influence on the physiological response. We also present an 'adsorbome' of 125 plasma proteins that are known to associate with nanomaterials. We further describe how the protein corona is related to the synthetic identity of a nanomaterial, and highlight efforts to control protein nanomaterial interactions. We conclude by discussing gaps in the understanding of protein-nanomaterial interactions along with strategies to fill them (167 references). PMID- 22086678 TI - Identification of cancer patients with Lynch syndrome: clinically significant discordances and problems in tissue-based mismatch repair testing. AB - Tissue-based microsatellite instability (MSI) analysis and immunohistochemistry for DNA mismatch repair proteins are accepted screening tools to evaluate patients with cancer for Lynch syndrome. These laboratory analyses are thus important tools in cancer prevention. Quality assurance review was conducted to identify test discordances and problems. These results were then analyzed in conjunction with genetic testing outcomes. Six hundred and forty-six consecutive tumors from 2002 to 2010 were examined. MSI-low tumors were excluded so that 591 tumors comprised the final analyses. Discordance was defined as a discrepancy between immunohistochemical and MSI analysis. Problem was defined as indeterminate or questionable immunohistochemical or MSI results. All results and clinical and family histories were centrally reviewed by two pathologists and one genetics counselor. Discordances and problems were identified in 23 of 591 (3.9%) of the tumors. Twelve of 102 MSI-high carcinomas (11.8%) and one of 489 microsatellite stable tumors had discordant immunohistochemistry. Of these 13 tumors, 11 were from patients who had personal and/or family cancer histories concerning for a germline mismatch repair gene mutation. In addition to discordances, 10 tumors with problematic immunohistochemical profiles were identified. Accurate evaluation of MSI was possible in all tumors. In summary, concordance between immunohistochemistry and MSI was high, particularly for tumors that are microsatellite stable. Greater frequency of test discordance was identified in the tumors that were MSI-high. Thus, a major consequence of the use of immunohistochemistry by itself as a screen is the failure to identify colorectal and endometrial cancer patients who likely have Lynch syndrome. PMID- 22086679 TI - N-nitroso-tris-chloroethylurea induces premalignant squamous dysplasia in mice. AB - Squamous cell carcinoma (SCC) and premalignant endobronchial lesions have been difficult to study in murine models. In this study, we evaluate the topical N nitroso-tris-chloroethylurea (NTCU) murine SCC model, determine the extent to which resulting premalignant airway dysplasia develops, discuss clinicopathologic grading criteria in lesion progression, and confirm that immunohistochemical (IHC) staining patterns are consistent with those observed in human endobronchial dysplasia and SCC. Male and female FVB mice were treated biweekly with topical NTCU (4, 8, or 40 mmol/L) or vehicle for 32 weeks. Following sacrifice, squamous cell lesions were enumerated and categorized into the following groups: flat atypia, low-grade dysplasia, high-grade dysplasia, and invasive SCC. The 40 mmol/L NTCU concentration produced the entire spectrum of premalignant dysplasias and squamous cell carcinomas, but was associated with poor survival. Concentrations of 4 and 8 mmol/L NTCU were better tolerated and produced only significant levels of flat atypia. Squamous origin of the range of observed lesions was confirmed with IHC staining for cytokeratin 5/6, p63, thyroid transcription factor-1 (TTF-1), and Napsin-A. This study shows that topical application of high-dose NTCU produces endobronchial premalignant lesions with classic squamous characteristics and should allow for improved preclinical evaluation of potential chemopreventive agents. PMID- 22086680 TI - Organ specificity of the bladder carcinogen 4-aminobiphenyl in inducing DNA damage and mutation in mice. AB - Aromatic amines are a widespread class of environmental contaminants present in various occupational settings and tobacco smoke. Exposure to aromatic amines is a major risk factor for bladder cancer development. The etiologic involvement of aromatic amines in the genesis of bladder cancer is attributable to their ability to form DNA adducts, which upon eluding repair and causing mispairing during replication, may initiate mutagenesis. We have investigated the induction of DNA adducts in relation to mutagenesis in bladder and various nontarget organs of transgenic Big Blue mice treated weekly (i.p.) with a representative aromatic amine compound, 4-aminobiphenyl (4-ABP), for six weeks, followed by a six-week recovery period. We show an organ-specificity of 4-ABP in inducing repair resistant DNA adducts in bladder, kidney, and liver of carcinogen-treated animals, which accords with the bioactivation pathway of this chemical in the respective organs. In confirmation, we show a predominant and sustained mutagenic effect of 4-ABP in bladder, and much weaker but significant mutagenicity of 4-ABP in the kidney and liver of carcinogen-treated mice, as reflected by the elevation of background cII mutant frequency in the respective organs. The spectrum of mutations produced in bladder of 4-ABP-treated mice matches the known mutagenic properties of 4-ABP-DNA adducts, as verified by the preponderance of induced mutations occurring at G:C base pairs (82.9%), with the vast majority being G:C >T:A transversions (47.1%). Our data support a possible etiologic role of 4-ABP in bladder carcinogenesis and provide a mechanistic view on how DNA adduct-driven mutagenesis, specifically targeted to bladder urothelium, may account for organ specific tumorigenicity of this chemical. PMID- 22086682 TI - Sutureless compression anastomosis with a biofragmentable anastomosis ring. AB - BACKGROUND/AIMS: Many studies have reported the safety and effectiveness of biofragmentable anastomotic rings (BARs). However, these devices are not widely used, especially in Japan. Therefore, we considered the clinical benefits of BARs and the reasons for their unpopularity. METHODOLOGY: We retrospectively examined 61 patients who underwent sigmoidectomy (34 patients) or high anterior resection (HAR) (27 patients). The patients were divided into 4 groups: sigmoidectomy and anastomosis with a BAR (SB group), sigmoidectomy and anastomosis with an end-to end (EEA) stapler (SE group), HAR and anastomosis with a BAR (HARB group), and HAR and anastomosis with an EEA stapler (HARE group). RESULTS: The time required for anastomosis was significantly lower in the HARE group than in the HARB group. The incidence of anastomotic stricture formation was significantly lower in the HARB group, however the duration of hospitalization after surgery was significantly longer in the HARB group rather than in the HARE group. CONCLUSIONS: BARs are unpopular because of the long interval between surgery and the passage of the device in the feces, and because compared to BARs, staplers are easy to manipulate in the narrow pelvic space. PMID- 22086681 TI - Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells. AB - Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, which is, in part, due to intrinsic (de novo) and extrinsic (acquired) resistance to conventional therapeutics, suggesting that innovative treatment strategies are required for overcoming therapeutic resistance to improve overall survival of patients. Oral administration of metformin in patients with diabetes mellitus has been reported to be associated with reduced risk of pancreatic cancer and that metformin has been reported to kill cancer stem cells (CSC); however, the exact molecular mechanism(s) has not been fully elucidated. In the current study, we examined the effect of metformin on cell proliferation, cell migration and invasion, and self-renewal capacity of CSCs and further assessed the expression of CSC marker genes and microRNAs (miRNA) in human pancreatic cancer cells. We found that metformin significantly decreased cell survival, clonogenicity, wound-healing capacity, sphere-forming capacity (pancreatospheres), and increased disintegration of pancreatospheres in both gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells. Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR 101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres. We also found that reexpression of miR-26a by transfection led to decreased expression of EZH2 and EpCAM in pancreatic cancer cells. These results clearly suggest that the biologic effects of metformin are mediated through reexpression of miRNAs and decreased expression of CSC-specific genes, suggesting that metformin could be useful for overcoming therapeutic resistance of pancreatic cancer cells. PMID- 22086683 TI - Preperitoneal approach for femoral hernia repair. AB - BACKGROUND/AIMS: Although Lichtenstein's procedure is the standard procedure in surgical hernia treatment, and the role of laparoscopic hernia repair is constantly increasing, preperitoneal approach for femoral hernia repair should be equally considered. METHODOLOGY: After the horizontal incision of transversal fascia, preperitoneal space is visualized. The hernial sac is opened and its content is placed in the abdominal cavity, or if there is a need, resection is performed. Once the peritoneum is sutured, the iliopubic tract and Cooper's ligament are bridged with two or three sutures in the medial portion of the femoral ring. RESULTS: From 1998 to 2008, 94 patients were treated for femoral hernia using the preperitoneal approach. Out of 94 participants, 86 were female. Intestinal obstruction was present in 48 cases. Resection of the small intestine or omentum was performed in 40 patients. There was no perioperative mortality. We observed early postoperative complications in 4 patients. Following the procedure, there was no recurrence of the femoral hernia. CONCLUSIONS: We found that preperitoneal repair is the method of choice in surgical treatment of femoral hernia. The surgical technique is simple and feasible, while fully acknowledging the functional anatomy of the inguinofemoral region and the etiology of the condition. PMID- 22086684 TI - Elevated C-reactive protein level is associated with the tumor depth of invasion in patients with operable colorectal carcinoma. AB - BACKGROUND/AIMS: There is increasing evidence to show that the presence of raised concentrations of serum C-reactive protein (CRP) is associated with poor survival in patients with colorectal carcinoma. The CRP response with respect to tumor characteristics in colorectal carcinoma was examined to identify factors that might reflect a raised CRP level. METHODOLOGY: One hundred and eighty-one patients who underwent elective colorectal resection were identified for inclusion in this study. Eighteen patients with high CRP levels were compared to a control group of 163 patients without high CRP levels, and the correlation between preoperative CRP level and clinicopathological features in operable colorectal carcinoma was investigated. RESULTS: The analysis of factors with seeming potential to be associated with CRP levels following colorectal surgery, disclosed that only the depth of tumor invasion, serum albumin and lymphovascular invasion were of statistical significance. Multivariate subgroup analysis of the association between these factors and CRP showed that depth of invasion and albumin were independently associated with CRP. CONCLUSIONS: Our results suggest that depth of tumor invasion is associated with an increase in CRP levels. CRP is considered an important indicator of advanced local invasion in operable colorectal surgery, if other inflammatory conditions are excluded. PMID- 22086685 TI - Microsatellite instability in young patients with sporadic colorectal adenomas. AB - BACKGROUND/AIMS: This study was designed to determine the prevalence of microsatellite instability (MSI) among colorectal adenomas detected in patients <= 40 years of age and to compare the prevalence of MSI in young (<= 40 years) and older (>40 years) patients with colorectal adenomas. Additionally, we attempted to identify the underlying cause of MSI in these patients. METHODOLOGY: We prospectively tested for the presence of MSI using five NCI markers in samples from the two patient groups. The frequency of MSI was compared and the underlying causes of MSI were determined by methylation specific PCR and germ-line mutation analysis for mismatch repair genes. RESULTS: The frequency of MSI was higher in the <= 40 group than the >40 group (31.4% and 6.4%, respectively, p=0.0004). The MSI-high pattern was also more prevalent in the <= 40 group than the >40 group (15.7% and 2.5%, respectively, p=0.014). The hypermethylated hMLH1 gene was demonstrated in 7/8 (87.5%) patients with MSI-high in the <= 40 group and in 1/2 (50.0%) patients with MSI-high in the >40 group. No study subject showed a germline mutation of hMLH1 or hMSH2. CONCLUSIONS: MSI-high was more frequent in young (<= 40 years) patients with colorectal adenoma than in older (>40 years) patients. Hypermethylation of the hMLH1 gene appears to be an important cause of MSI-high in these patients. PMID- 22086686 TI - Prognostic significance of heat shock protein 110 expression and T lymphocyte infiltration in esophageal cancer. AB - BACKGROUND/AIMS: Heat shock proteins (HSPs) are well known as tumor rejection antigens, most notable of which is HSP70. HSP110 is classified as a member of the HSP70/DnaK superfamily. The objective of this study was to clarify the clinicopathological and prognostic significance of Heat Shock Protein 110 expression and T lymphocyte infiltration in esophageal cancer. METHODOLOGY: Immunohistochemical staining of HSP110, CD4 and CD8 were performed on surgical specimens obtained from 124 patients with esophageal cancer. RESULTS: The expression of HSP110 correlated inversely with depth of invasion (p<0.0001), lymph node metastasis (p=0.0163), pathological stage (p<0.0001), lymphatic invasion (p=0.0104), blood vessel invasion (p=0.0027), infiltrative growth pattern (p=0.0368) and correlated positively with CD4+ T lymphocyte infiltration (p=0.0018). Reduction of HSP110 expression was significantly correlated with poor prognosis (p=0.0010). CONCLUSIONS: The present findings suggest that HSP110 expression and T lymphocyte infiltration is a significant prognostic factor for esophageal cancer. PMID- 22086687 TI - Therapeutic strategy for esophageal cancer based on solitary lymph node metastasis. AB - BACKGROUND/AIMS: It is essential to perform appropriate lymph node dissection in esophageal cancer. However, it may be beneficial if lymph node dissection could be minimized to reduce the surgical stress. METHODOLOGY: Between April 1992 and March 2005, 121 esophageal cancer patients (42 patients with solitary lymph node metastasis and 79 N0 patients) were enrolled. The survival time, distribution of solitary lymph node metastasis and the pattern of recurrence were evaluated. RESULTS: The distribution of solitary lymph node metastasis was extensively observed in cervical, thoracic and abdominal cavities and the site of lymph node recurrence could even be detected in non-regional lymph nodes in N0 patients. It was difficult to predict the site of initial lymph node metastasis in patients with esophageal cancer. CONCLUSIONS: Systemic lymph node dissection for regional lymph nodes is recommended for resectable esophageal cancer as the concept of sentinel lymph nodes has not yet been proven. PMID- 22086688 TI - Influence of neutrophil elastase inhibitor on the postoperative course in patients with esophageal cancer after transthoracic esophagectomy. AB - BACKGROUND/AIMS: We evaluated influence of sivelestat sodium hydrate in the clinical course after transthoracic esophagectomy. METHODOLOGY: Forty-two consecutive patients with esophageal cancer underwent transthoracic esophagectomy. Twenty-two patients were treated with sivelestat (sivelestat group) and twenty patients were untreated (control group). Sivelestat (0.2 mg/(kg.h)-1) was continuously administered for 5 days since ICU admission. Postoperative morbidity, duration of systemic inflammatory response syndrome (SIRS) and mechanical ventilation, and the time to refilling were examined. The level of serum white blood cells (WBC), C-reactive protein (CRP), aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin (TB) and the PaO2/FiO2 ratio were measured. RESULTS: The durations of SIRS and mechanical ventilation and the time to refilling were significantly shorter in the sivelestat group than in the control group. Postoperative changes in the serum WBC, CRP, AST and ALT levels were not significantly different between the groups; however, serum TB level was significantly lower in the sivelestat group than in the control group. The PaO2/FiO2 ratio at postoperative day 3 was significantly higher in the former than in the latter. CONCLUSIONS: We demonstrated that sivelestat might contribute to the improvement of acute lung injury, hyperbilirubinemia and postoperative circulatory failure. PMID- 22086689 TI - Long-term survival and improved quality of life after chemoradiotherapy to treat esophageal small cell carcinoma: a report of two cases. AB - In case 1, endoscopy revealed a submucosal tumor with central ulceration in the esophagus of a 54- year-old man. A biopsy specimen revealed small cell carcinoma without metastasis and the stage of the cancer was stage I (T2N0M0). Two cycles of concurrent cisplatin, etoposide and radiotherapy resulted in an incomplete response/stable disease. The tumor recurred and had metastasized to the brain, lung, liver, lymph nodes of the mediastinum, abdomen and bones after six cycles. Two cycles of irinotecan and cisplatin then elicited a complete response in the primary esophageal lesion. However, progressive disease was identified in the metastatic bone tumors. Despite two further cycles of therapy, he died 447 days after the initial course. In case 2, a biopsy specimen of a tumor with central ulceration in the esophagus of a 77-year old man with swallowing difficulty indicated small cell carcinoma. The stage of the cancer was diagnosed as stage II (T3N0M0). Two cycles of irinotecan, cisplatin and concurrent radiotherapy elicited a complete response. However, the tumor metastasized to the brain and the liver 644 days after starting treatment. Two cycles of carboplastin plus irinotecan elicited a partial response in the metastatic tumors, but he died 988 days after starting chemotherapy. PMID- 22086690 TI - Prognostic factors in gastrointestinal perforation. AB - BACKGROUND/AIMS: Postoperative complications associated with gastrointestinal (GI) perforation may lead to a poor prognosis. The goal of the study was to identify factors required for the establishment of appropriate perioperative procedures in such cases. METHODOLOGY: The subjects were 51 patients with GI perforation treated from July 2007 to June 2008 in six hospitals in the Minamikawachi district. RESULTS: The perforation sites were the large intestine in 22 cases, small intestine in 15, stomach in 7 and duodenum in 7. Postoperative complications developed in 25 cases (49%), including infection in 20 and respiratory dysfunction in 13. Hospital mortality was 25% and the major causes of death were infection and respiratory dysfunction. The mortality was 52% and 0% in patients with and without postoperative complications, respectively. The mortality was 69% in the 13 patients with postoperative respiratory dysfunction compared to 11% for patients without respiratory dysfunction. Of the 7 patients with large intestine perforation, 4 were treated with sivelestat sodium. These 4 patients had a high mean SOFA score (11.5+/-1.3), but 2 out of 4 survived. CONCLUSIONS: Postoperative complications occurred in approximately half of the patients with GI perforation and were associated with a poor prognosis. Prevention of respiratory dysfunction is particularly important for an improvement of outcome. PMID- 22086691 TI - Prognostic impact of lymph node metastasis along the left gastric artery in gastric cancer. AB - BACKGROUND/AIMS: This present study investigated a prognostic impact of the lymph nodes along left gastric artery metastases in gastric cancer patients. METHODOLOGY: In this study we analyzed 189 patients with N1 and N2 (Japanese Classification for Gastric Cancer: JCGC) metastasis. The N2 patients were divided into two subgroups; patients with N1 + metastases along left gastric artery (No.7) (only No.7-positive N2), and the remaining N2 patients (Remaining N2). We compared the clinicopathological factors and prognoses among these patient groups. RESULTS: Patients in the Only No.7-positive N2 subgroup showed a better survival curve than the Remaining N2 subgroup although the difference was not significant. In TNM-N1 (six or less), the survival curves of Only No.7-positive N2 were better than those of Remaining N2. However, the Only No.7-positive N2 and Remaining N2 subgroups both showed similar survival outcomes for TNM-N2 (seven or more). CONCLUSIONS: The prognostic impact of lymph node metastases along the left gastric artery was found to be rather close to JCGC N1 (peri-gastric nodes) than JCGC N2 in patients with gastric cancers, especially in cases in which the total number of positive lymph nodes was six or less. PMID- 22086692 TI - Acute respiratory distress syndrome after gastrointestinal surgery. AB - BACKGROUND/AIMS: Acute respiratory distress syndrome (ARDS) occasionally occurs after gastrointestinal surgery involving severe inflammation such as diffuse peritonitis. Management of this condition has been difficult and effective therapies have not yet been established. In the present study the management for ARDS after gastrointestinal surgery was evaluated. METHODOLOGY: A total of 15 patients developed ARDS after gastrointestinal operations performed in our institution. The mean patient age was 75.4+/-11.1 years. Onset of ARDS occurred <=24 hours postoperatively in 12 patients and 3- 11 days postoperatively in 3 patients. Treatment for ARDS comprised continuous hemodiafiltration (CHDF), high dose glucocorticoid therapy or administration of a neutrophil elastase inhibitor (sivelestat). RESULTS: Four patients died 3-45 days after onset of ARDS (mortality rate, 26.6%). CHDF was performed in 12 patients, 8 patients received highdose glucocorticoid therapy and 11 patients received sivelestat. No differences in severity scores and clinical data were noted between survivors and non-survivors. PaO2/FiO2 ratio was significantly lower in non-survivors than in survivors from 5 days after starting treatment, whereas no difference was apparent at the onset of ARDS. CONCLUSIONS: Multimodal therapies for ARDS were effective. Longitudinal fluctuation in PaO2/ FiO2 ratio after starting treatment appears to offer a prognostic factor for ARDS. PMID- 22086693 TI - Assessment of the ablated area after radiofrequency ablation by the spread of bubbles: comparison with virtual sonography with magnetic navigation. AB - BACKGROUND/AIMS: The purpose of this study was to investigate whether bubble images after radiofrequency ablation (RFA) can predict the ablated area. METHODOLOGY: The spread of bubbles 5 minutes after RFA were compared with the unenhanced area of virtual sonography with magnetic navigation in two RFA methods: expandable needle and cool-tip needle. RESULTS: Thirty-one hepatocellular carcinoma nodules were treated by RFA with either an expandable needle or cool-tip needle (n=14 and n=17, respectively) and examined. In the 14 nodules treated by expandable needle, bubble images (puncture direction; r=0.833, p=0.0002, perpendicular direction; r=0.803, p=0.0005) were closely correlated with the unenhanced area of virtual sonography. On the other hand, in 17 nodules treated by cool-tip needle, there was no correlation between the bubble images and virtual sonography (puncture direction; r=0.590, p=0.0127, perpendicular direction; r=0.342, p=0.180). CONCLUSIONS: The observation of bubbles with the expandable needle can accurately predict the ablated area and is helpful for assessing local control of RFA. PMID- 22086694 TI - Clinical significance of core gene mutations during the course of genotype C chronic hepatitis B virus infection. AB - BACKGROUND/AIMS: The aim of this study was to investigate the association of HBV core gene mutations with disease severity in HBV-infected patients. METHODOLOGY: We included 249 genotype C HBV infected patients: 39 asymptomatic carriers (AC), 68 with chronic hepatitis (CH), 75 with liver cirrhosis (LC), and 67 with HCC. HBV DNA was extracted from patient sera and the HBV core gene was analyzed by PCR and sequencing. RESULTS: The overall frequency of a codon substitution, which was caused by a missense mutation in the HBV core region, was 4.5+/-9.0/patient. The codon substitutions were predominantly clustered in the mid-core regions; 22.3% of codon substitutions were found in codons 13, 87, 97 and 130. The rate of substitution for codon 13 was higher in CH and LC than in AC. For codons 87 and 130, AC had a lower substitution rate compared to the other 3 groups. The substitution rate for codon 97 was higher in CH and HCC than in AC. CONCLUSIONS: Core gene mutations were frequently detected during the course of chronic HBV infection, and some mutational hot spots were correlated with severe forms of disease. Thus, these mutations might play a pathophysiological role in the disease progression in HBV infected patients. PMID- 22086695 TI - Pegylated interferon alfa-2B for chronic delta hepatitis: 12 versus 24 months. AB - BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of pegylated interferon (PEG-IFN) alfa-2b for short (one year) and long (two years) terms of treatment for chronic hepatitis D. METHODOLOGY: Eighteen patients with chronic hepatitis D were administered PEG-IFN alfa-2b 1.5MUg/kg twice weekly for 1 month, after which they were randomly assigned (2:1) to receive PEG-IFN alfa-2b 1.5MUg/kg/wk for an additional 23 months (n=11; group 1) or 11 months (n=7; group 2). All patients were followed-up for 6 months after completing therapy. RESULTS: In group 1, there was no significant difference between HDV-RNA and ALT levels at follow-up compared with baseline (p=0.219 and p=0.624, respectively). However, in group 2, HDVRNA levels, but not ALT levels, were significantly lower at the end of follow-up (EOF) than at baseline (p=0.016 and p=0.237, respectively). Three patients, all in group 2, had undetectable hepatitis B surface antigen (HBsAg) at the end of followup (EOF). However, there was no patient who had undetectable HBsAg in group I (p=0.043). There were statistical differences for all 18 patients in terms of baseline levels of HDV-RNA compared to end of treatment (EOT) (p=0.021) and EOF (p=0.003). CONCLUSIONS: Extending therapy from 12 to 24 months conferred no additional advantage in terms of HDV-RNA suppression and ALT normalisation. PMID- 22086696 TI - HCC influence on patient survival after liver transplantation for HDV cirrhosis. AB - BACKGROUND/AIMS: The effect of hepatocellular cancer (HCC) in patients transplanted for hepatitis B and D virus (HB/DV) cirrhosis is not well studied. Our aim was to study the long-term survival outcomes of patients who underwent liver transplantation for HB/DV cirrhosis with and without HCC. METHODOLOGY: A total of 231 primary, adult, single- organ liver transplants were performed from 1990 to 2007. HB/DV was the cause of cirrhosis in 36 patients. Nine patients died during the first 3 postoperative months from surgical complications. The study group comprised the remaining 27 patients. The median follow-up was 1515 days. RESULTS: The mean patient survival was 3760 days (95% CI: 3013-4507). Six patients were diagnosed with HCC. The mean patient survival was 3011 days (95% CI: 2344-3679) and 4036 days (95% CI: 3002-5070) for recipients without and with HCC, respectively. For the same groups, the incidence of microbial infections was 61.9% and 33.3%, respectively (p=0.219). HCC has not recurred in any of the six patients. CONCLUSIONS: The mean long-term survival after liver transplantation for HB/DV and HCC surpassed 11 years. The superior survival of HCC patients is difficult to explain. The increased number (almost double) of microbial infections in the non- HCC population might be held accountable. PMID- 22086697 TI - Drainage patterns of right and accessory hepatic veins: anatomical-functional classification derived from 3-dimensional CT reconstructions. AB - BACKGROUND/AIMS: Inadequate knowledge of the right (RHV) and accessory (IHV) hepatic 'venous drainage' territories can lead to severe postoperative venous congestion after right graft live donor liver transplantation. The purpose of our study was to define the anatomical-functional RHV and IHV drainage territories. METHODOLOGY: One hundred and forty consecutive live liver donor candidates were evaluated by means of 3-D CT reconstructions and 3-D virtual hepatectomies. Three RHV/IHV drainage patterns were identified and 'risky' configurations for right graft resections were defined. RESULTS: Livers with 'small' IHV drainage volumes (90.1+/-63.2mL) had dominant type IRHV/ IHV or non-dominant type III-RHV/IHV total liver (TL) complexes. All other cases had 'large' IHV volumes (294.7+/ 115.5mL, p<0.001) with dominant type II-RHV/IHV TL complexes. Loss of IHV drainage volume (such as with no IHV reconstruction) in these cases was associated with a 'dominance transition' from right (RHV) to middle (MHV) hepatic veins, placing the grafts at 'high risk' for venous congestion. CONCLUSIONS: Type II-RHV/IHV complexes with large IHV drainage volumes are at 'high risk' for venous congestion in live donor liver transplantation. PMID- 22086698 TI - Postoperative infectious and non-infectious complications after hepatectomy for hepatocellular carcinoma. AB - BACKGROUND/AIMS: Hepatic resection for hepatocellular carcinoma (HCC) is associated with a relatively high morbidity rate. This study investigated risk factors for morbidity after resection of HCC that were related to perioperative management and operative techniques. METHODOLOGY: Five hundred and thirty HCC patients who underwent hepatectomy between 1992 and 2008 were divided into three groups: 51 patients with infectious complications during their hospital stay (infectious group), 67 patients with non-infectious complications (non-infectious group) and 412 patients without complications who were discharged within 21 days after hepatectomy (uncomplicated group). RESULTS: Non-infectious complications decreased significantly over time. Although infectious complications also decreased, the change was not significant. The overall survival rate of the groups with complications was significantly worse than that of the uncomplicated group (p<0.0005). Univariate and multivariate analyses showed that an operating time >300min and bile leakage were independent risk factors for infectious complications, while a platelet count <=13x104/mL, cirrhosis and operative blood loss >1,000mL were risk factors for non-infectious complications. CONCLUSIONS: To achieve zero morbidity, it is important to avoid bile leakage and minimize blood loss during resection of HCC in patients with cirrhosis. PMID- 22086699 TI - Effect of beta -catenin siRNA on proliferation and apoptosis of hepatoma cell line SMMC-7721 and HepG-2. AB - BACKGROUND/AIMS: The aim of this study was to investigate the effect of expression of siRNA beta- catenin silent gene on cell cycle and apoptosis of different hepatoma cells. METHODOLOGY: The effect of the beta-catenin-siRNA recombinant plasmid on the growth of different hepatoma cells was observed by MTT assays; and the effect of the recombinant plasmid on proliferation and apoptosis of different hepatoma cells was detected through flow cytometry. RESULTS: Transfection of the beta-catenin-siRNA recombinant plasmid into hepatoma cells significantly inhibited beta-catenin expression at protein and mRNA levels (p<0.05) as shown by western blotting and RT-PCR, respectively. The MTT assay showed that beta-catenin-siRNA can significantly inhibit growth of hepatoma cells. The results of flow cytometry showed that the growth of different hepatoma cells was blocked at G0/G1 phase and compared with the control group there was a significant difference (p<0.05). Flow cytometry also showed that apoptosis of different hepatoma cells, compared with the control group, was significantly different (p<0.05). CONCLUSIONS: Inhibition of beta-catenin in hepatoma cells can inhibit growth and promote apoptosis, and there was difference in the effect on proliferation and apoptosis between different hepatoma cells. PMID- 22086700 TI - Delayed bile leak with avastin after liver resection for metastatic colorectal cancer. AB - Chemotherapy for metastatic colorectal cancer is constantly advancing. Its use in the adjuvant and neoadjuvant setting is also increasing. However, while long-term survival is improving, clinicians must be aware of the possible adverse events that can occur when treating with adjuvant chemotherapy and liver resection. We present a case of a life-threatening delayed bile leak following a liver resection for metastatic colorectal cancer in association with adjuvant treatment with bevacizumab. A 53-year-old man was treated with neoadjuvant bevacizumab followed by liver resection for metastatic colorectal cancer. He made an uneventful recovery. Forty-three days post-surgery he received bevacizumab and developed acute life-threatening bile leaks from the cut surface of the liver. He spent a total of 65 days in hospital, and required ERCP repeatedly and eventually had a repeat liver resection to resolve the bile leak. This case reports a possible association between bevacizumab and a life threatening delayed bile leak following liver resection. PMID- 22086701 TI - Laparoscopic cystogastrostomy via the posterior approach for pancreatic pseudocyst drainage. AB - BACKGROUND/AIMS: The treatment of pancreatic pseudocysts is still being debated. Laparoscopic treatment of pancreatic pseudocysts enables definitive drainage with faster recovery. Moreover, the best drainage technique for pseudocysts located adjacent to the posterior gastric wall is pseudocystgastrostomy. Although, drainage via the anterior approach has been frequently reported, reports on the posterior approach are rare. Here, we evaluated the efficacy of the posterior approach technique for pancreatic pseudocyst drainage. METHODOLOGY: We retrospectively studied 28 patients who underwent cystogastrostomy for pancreatic pseudocysts: they were divided into the conventional cystogastrostomy group (CCG group) and the laparoscopic cystogastrostomy via the posterior approach group (LCGP group). RESULTS: The mean operative time was significantly shorter, blood loss was significantly reduced, and the duration of hospitalization after surgery was significantly shorter in the LCGP group than in the CCG group. Recurrence was observed in 1 patient (5.6%) in the CGP group; it was an asymptomatic recurrence that did not require additional treatment. In contrast, there was no recurrence in the LCGP group patients. CONCLUSIONS: We think that our technique of performing laparoscopic cystogastrosotmy via the posterior approach is easy and feasible for pancreatic pseudocyst drainage. PMID- 22086702 TI - Molecular profile of apomucin and p53 protein as predictors of malignancy in intraductal papillary mucinous neoplasms of the pancreas. AB - BACKGROUND/AIMS: Invasive intraductal papillary mucinous neoplasms (IPMNs) of the pancreas show poor prognosis similar to ductal adenocarcinomas. The aim of this study was to evaluate the molecular indicators of invasion and risk factors of recurrence of IPMNs. METHODOLOGY: For 46 curative resections of IPMNs, we analyzed the expression of apomucin antigens (MUC1, MUC2 and MUC5AC), p53 and Ki67 using resected specimens. RESULTS: All 46 IPMNs were classified into 4 groups; MUC1+/p53+, MUC1+/p53-, MUC2+ and MUC1-/MUC2-. The incidence of MUC1 expression increased according to the grade of dysplasia and all of 5 invasive carcinomas expressed MUC1. None of the invasive carcinoma, but almost half of IPMNs of non-invasive carcinoma and sever dysplasia expressed MUC2. Additionally, p53 expression was limited to invasive IPMNs and a non-invasive IPMN which recurred after the operation. The Ki67 labeling index was increased according to the grade of dysplasia and was highest in the MUC1+/p53+ group. In the MUC2+ cases, Ki67 labeling index was significantly higher than that in the MUC1-/MUC2- cases. MUC5AC was expressed in all IPMNs. CONCLUSIONS: The expression of MUC1, MUC2 and p53 might be indicators of malignancy and the expressions of MUC1 and p53 were the predictors of tumor invasion and recurrence. PMID- 22086703 TI - Modified Cattell's reconstruction with pancreaticogastrostomy following pylorus preserving pancreaticoduodenectomy for a patient with gastroptosis. AB - Gastroptosis is a condition in which the stomach is enlarged and located in an abnormally low position, which impedes normal stomach function. A patient with gastroptosis has equivocal complaints such as nausea, stomach fullness and abdominal pain. Pylorus-preserving pancreaticoduodenectomy (PPPD) has a better outcome than the Whipple procedure in terms of operative mortality and morbidity, and postoperative nutritional state. However, delayed gastric emptying (DGE) is frequently observed after PPPD. If PPPD is performed for a patient with gastroptosis, the risk of postsurgical DGE may increase. Therefore, we have developed a modified Cattell's reconstruction with pancreaticogastrostomy (PG) after PPPD to prevent DGE in a patient with gastroptosis and adenocarcinoma of the ampulla of Vater. PMID- 22086704 TI - Robotic central pancreatectomy with pancreaticogastrostomy (transgastric approach) in a solid pseudopapillary tumor of the pancreas. AB - Function preserving minimal invasive pancreatectomy is thought to be ideal approach for benign and borderline malignant tumors of the pancreas because these tumors can be expected for longterm survival. Pancreatic tumor in the neck of the pancreas is a challenging issue. Pancreaticoduodenectomy and distal pancreatectomy with/without splenectomy are the usual modes of surgery for them. Central pancreatectomy is a rare surgical procedure, even in open surgery. With the development of laparoscopic experiences, a few cases of laparoscopic central pancreatectomy have begun to be reported, but they are believed to be still demanding tremendous laparoscopic skills and experiences. However, advancements in technology have encouraged surgeons to overcome the limitations of conventional laparoscopic surgery. Herein, we report a case of robot-assisted central pancreatectomy with pancreaticogastrostomy (transgastric approach). Wrist like movements of effector instruments and stable 3-D visualization provided by the robot surgical system are believed to enhance the precise and safe laparoscopic performance. More experiences need to be accumulated in order to evaluate the real value of robot pancreatic surgery. PMID- 22086705 TI - Successful neoadjuvant treatment with radiochemotherapy and systemic chemotherapy for the locally advanced pancreatic head cancer: report of a case. AB - A 49-year-old man was admitted to the hospital for the upper abdominal pain and was diagnosed as unresectable pancreatic head cancer because of the invasion around the superior mesenteric artery. He was treated with radiochemotherapy, followed by systemic gemcitabine alone for 3 courses. He was further treated with systemic gemcitabine plus S-1 combination therapy for 5 courses. CT examination after these treatments showed a dramatic reduction of the tumor at the head of the pancreas and a pancreatoduodenectomy was performed. Pathologically, there was no residual malignant tumor. He has had no recurrent tumor up until now. Several studies of gemcitabine plus S-1 combination therapy show higher response rates for unresectable tumors. The current case indicates the effectiveness of the radiochemotherapy and gemcitabine plus S-1 combination therapy for locally advanced pancreatic head cancer as a neoadjuvant setting. We consider that multidisciplinary treatment including gemcitabine plus S-1 therapy may prolong the survival time by curative operation. PMID- 22086706 TI - Prognostic significance of CD83 positive tumor-infiltrating dendritic cells and expression of TGF-beta 1 in human gastric cancer. AB - BACKGROUND/AIMS: In this study we analyzed the significance of CD1a and CD83 positive tumor infiltrating dendritic cells (TIDCs) and the expression of TGF beta1 in gastric cancer tissue, and their relationship with disease progression and prognosis of patients. METHODOLOGY: The immunohistochemical expression of CD1a, CD83 and TGF-beta1, was evaluated in 55 patients with gastric cancer and followed-up for five years. RESULTS: We found tumor infiltration with CD1a and CD83 positive DCs in all 55 cases and cytoplasmic TGF-beta1 immunoreactivity in tumor cells in 76.4% of cases. TGF-beta1 expression correlated to low CD83 positive DCs in 100% of the samples (chi2=7.66; p=0.022). Low CD83 positive DCs in tumor border (chi2=15.38; p<0.001) was also observed in 100% of tumors with TGF-beta1 expression. The number of CD1a and CD83 positive TIDCs in the tumor border was inversely correlated with positive lymph node metastases (chi2=6.64; p=0.036 and chi2=6.44; p<0.04, respectively). Patients with a low number of tumor infiltrating CD83 positive DCs had shorter survival rates (p=0.022) and patients with TGF-beta1 expression had a worse prognosis after surgical therapy (p=0.017). CONCLUSIONS: Our results suggest that tumor infiltration with DCs may be of great importance in initiating the primary anti-tumor immune response. In patients with resectable gastric cancer, the grade of TIDCs and TGF-beta1 expression could be a useful predictor of prognosis. PMID- 22086707 TI - Laparoscopic transhiatal approach for cardiac cancer with lower esophageal invasion for patients with compromised respiratory function. AB - BACKGROUND/AIMS: The thoracoabdominal approach with extended abdominal incision and a left thoracotomy is the traditional approach for the treatment of cardiac cancer with lower esophageal invasion. However, this procedure entails high morbidity and mortality. We evaluated the effectiveness of the laparoscopic transhiatal approach without a thoracotmy. METHODOLOGY: We retrospectively analyzed the data obtained from 40 patients who underwent total gastrectomy with lower esophagectomy for cardiac cancer with lower esophageal invasion. These patients were divided into 2 groups: patients who underwent surgery via the conventional thoracoabdominal approach with extended abdominal incision and a left thoracotomy group (CTA group) and patients who underwent surgery via the laparoscopic transhiatal approach without a thoracotomy group (LTH group). RESULTS: All the LTH group patients were successfully treated without a thoracotomy. The 1- second forced expiratory volume was significantly lower in LTH group than in CTA group. No difference was observed between the groups with respect to the mean length of resected esophagus. The LTH group patients did not develop postoperative pneumonia. CONCLUSIONS: The laparoscopic transhiatal approach is safe and feasible for the resection of gastric cardiac cancer with lower esophageal invasion in patients with compromised respiratory function. PMID- 22086708 TI - Patellar tilt correlates with vastus lateralis: vastus medialis activation ratio in maltracking patellofemoral pain patients. AB - Patellofemoral (PF) pain is a common ailment of the lower extremity. A theorized cause for pain is patellar maltracking due to vasti muscle activation imbalance, represented as large vastus lateralis:vastus medialis (VL:VM) activation ratios. However, evidence relating vasti muscle activation imbalance to patellar maltracking is limited. The purpose of this study was to investigate the relationship between VL:VM activation ratio and patellar tracking measures, patellar tilt and bisect offset, in PF pain subjects and pain-free controls. We evaluated VL:VM activation ratio and VM activation delay relative to VL activation in 39 PF pain subjects and 15 pain-free controls during walking. We classified the PF pain subjects into normal tracking and maltracking groups based on patellar tilt and bisect offset measured from weight-bearing magnetic resonance imaging. Patellar tilt correlated with VL:VM activation ratio only in PF pain subjects classified as maltrackers. This suggests that a clinical intervention targeting vasti muscle activation imbalance may be effective only in PF pain subjects classified as maltrackers. PMID- 22086709 TI - Diabetes Cured by Pancreaticoduodenectomy: A Case Report of Glucagonoma Masquerading as Carcinoma of the Head of Pancreas. PMID- 22086710 TI - Primary Malignant Gastrointestinal Stromal Tumor (GIST) of the Gallbladder: Report of a Case. PMID- 22086711 TI - [Assessment of the psychic sequelae of traumatisation]. AB - This article deals with the question why experts quite frequently arrive at totally opposite judgements in clinical psychotraumatological expert opinions. This often leads to intense controversially conducted arguments resulting in lengthy proceedings. The reasons for this will be presented for two cases taken from expert opinions issued for the "Soziales Entschadigungs- und Auslanderrecht" (Laws for Social Reparations and Foreigners). A brief synopsis on the legal background will be given and solutions suggested. PMID- 22086712 TI - [Psychosocial functioning of adults with late diagnosed autism spectrum disorders -a retrospective study]. AB - BACKGROUND: The first time diagnosis of autism spectrum disorder (ASD) after passing childhood and adolescence is still considered a rare event. However, in recent years an increasing demand for diagnostic clarifications with suspected ASD in adulthood challenges this view. There is insufficient knowledge about the neuropsychological characterisation and psychosocial outcome of this adult subgroup in the autistic spectrum. AIM: To determine the psychosocial functioning (living status, partnerships, level of education, psychiatric history) of adult patients with late diagnosed ASD. METHODS: In a retrospective study, a chart review was conducted on 178 consecutively diagnosed individuals at a specialised outpatient clinic for adults with ASD. Global ratings of psychosocial functioning, assessment of psychiatric history and neuropsychological and psychopathological investigations were evaluated. RESULTS: The majority of patients (92 %) diagnosed with ASD suffered from high-functioning autism (HFA)/Asperger syndrome (AS) according to the criteria of ICD-10 (F84.5). The gender ratio was 2:1 favouring males. Mean age at diagnosis (34.1 +/- 9.5 years), general intelligence (HAWIE-R, global-IQ 115 +/- 20) and self-rated autistic symptoms (autism spectrum quotient [AQ] 39 +/- 6) were not discriminative to gender. The psychiatric history revealed a lifetime consultation rate of 78 %, most frequently with depression (50 %). The self-report instrument Beck depression inventory (BDI) identified 30 % of individuals presenting with depressive symptoms in clinical relevant intensity (BDI > 17). Achievement of an independent living status was reported by 68 % of individuals, 58 % reported about current or past intimate partnerships and almost two-thirds of the patients had achieved a higher educational status. DISCUSSION: The majority of ASD diagnosed late in lifetime turned out to be HFA/AS, presenting with high psychosocial adjustment with regard to independent living, educational status and partnerships. The high level of global intelligence supports the hypothesis of cognitively compensated autistic disturbances leading to the diagnosis comparably late in lifetime. The lifetime rate of psychiatric consultations is high, reflecting the importance to consider a diagnosis of ASD even late in life. PMID- 22086713 TI - [Images of the mind--what brain pictures really show]. AB - The use of imaging procedures brings with it legal consequences at different levels and in various relationships. As far as the generation of knowledge by means of imaging procedures is concerned, the problem of so-called incidental findings even now already demands a legally sound management in daily routine. Similarly, the use of imaging procedures in ongoing legal proceedings is of current relevance in cases when expert witnesses make use of the appropriate technologies for the formulation of their expertise. In contrast, lie detectors are far from any practical utility for forensic purposes. The major challenge in the next few years will be to investigate the scientific-medical knowledge gained from brain research concerning possible legal implications and to develop on this basis a practice-relevant and, if at all possible, proactive regulatory model. PMID- 22086714 TI - MicroCT detection of gunshot residue in fresh and decomposed firearm wounds. AB - Gunshot residue (GSR) evidence may be altered or obscured by after-death events such as putrefaction, autolysis, and/or damage by animals. The present study aimed at evaluating and comparing the amount and differential distribution of GSR utilizing microcomputed tomography (microCT) analysis of fresh and decomposed gunshot wounds. A total of 60 experimental shootings at three different firing distances (5, 15, and 30 cm) were performed on human calves surgically amputated for medical reasons. Thirty specimens (10 for each tested distance) were immediately formalin-fixed, while the other 30 specimens were enclosed in a cowshed for 15 days, before formalin fixation (air temperature ranging from 11 degrees C to 38 degrees C). MicroCT analysis with three-dimensional image reconstruction detected GSR particles in all the investigated entrance wounds. In fresh specimens, GSR was concentrated on the skin surface around the entrance hole and in the epidermis and dermis layers around the cavity, while in decomposed specimens, the high density particles were detected only in the dermis layer. No GSR was detected in exit wounds of both fresh and decomposed specimens regardless of the tested firing distance. Statistical analysis demonstrated that also in decomposed wounds the amount of GSR roughly correlated with the distance from which the gun was fired, exhibiting, however, a higher variability than in fresh samples. The obtained results suggest that microCT analysis can be a valid screening tool for differentiating decomposed entrance and exit gunshot wounds. PMID- 22086715 TI - Learning to fit in: an exploratory study of general perceived self efficacy in selected refugee groups. AB - As self efficacy beliefs help determine an individual's response to challenging situations, we explored the impact of the refugee experience on efficacy beliefs and their contribution to resettlement. General self efficacy (GSE) was assessed in 186 resettled Afghan and Kurdish refugees against a range of personal and temporal variables. Although no differences in GSE in relation to temporal factors were noted, significant relationships between self efficacy, lower psychological distress and higher subjective well being were evident. The findings suggest that GSE, because of its positive association with mental health and well being, is a variable worthy of further examination in refugees. In addition to ensuring a supportive environment for learning English, proactive employment strategies should be encouraged. Further research examining the use of successful refugee role models to promote self efficacy, enhance motivation for learning and ensure newly arrived refugees view resettlement as a challenge, rather than a threat, is recommended. PMID- 22086717 TI - Astragaloside IV attenuates complement membranous attack complex induced podocyte injury through the MAPK pathway. AB - Membranous nephropathy (MN) is the most common cause of idiopathic nephrotic syndrome in adults and the cause is known to be due to the injury of podocytes located in the glomeruli. Astragalus membranaceus has been used for the treatment of patients with MN in China for a long time. The beneficial effect of Astragalus membranaceus on proteinuria of patients with MN has been well documented. However, the mechanism of astragalus membranaceu in alleviation of MN is still not completely understood. Therefore, in the current study, we employed a podocyte injury model induced by complement membranous attack complex to examine the mechanism of astragalus membraneceus in the treatment of MN. We found that complement membranous attack complex could increase lactate dehydrogenase (LDH) release from podocytes and astragaloside IV (AS-IV) could prevent LDH release from podocytes in a time- and dose-dependent pattern. Moreover, AS-IV restored podocyte morphology and cytoskeleton loss induced by complement membranous attack complex. Furthermore, AS-IV was able to reduce phosphorylation of JNK and ERK1/2 induced by complement membranous attack complex. In conclusion, the mechanism of Astragalus membranaceus in the treatment of MN may be related to its attenuation of podocyte injury through regulation of cytoskeleton and mitogen activated protein kinase. PMID- 22086716 TI - Outcome-dependent sampling for longitudinal binary response data based on a time varying auxiliary variable. AB - Outcome-dependent sampling (ODS) study designs are commonly implemented with rare diseases or when prospective studies are infeasible. In longitudinal data settings, when a repeatedly measured binary response is rare, an ODS design can be highly efficient for maximizing statistical information subject to resource limitations that prohibit covariate ascertainment of all observations. This manuscript details an ODS design where individual observations are sampled with probabilities determined by an inexpensive, time-varying auxiliary variable that is related but is not equal to the response. With the goal of validly estimating marginal model parameters based on the resulting biased sample, we propose a semi parametric, sequential offsetted logistic regressions (SOLR) approach. The SOLR strategy first estimates the relationship between the auxiliary variable and the response and covariate data by using an offsetted logistic regression analysis where the offset is used to adjust for the biased design. Results from the auxiliary variable model are then combined with the known or estimated sampling probabilities to formulate a second offset that is used to correct for the biased design in the ultimate target model relating the longitudinal binary response to covariates. Because the target model offset is estimated with SOLR, we detail asymptotic standard error estimates that account for uncertainty associated with the auxiliary variable model. Motivated by an analysis of the BioCycle Study (Gaskins et al., Effect of daily fiber intake on reproductive function: the BioCycle Study. American Journal of Clinical Nutrition 2009; 90(4): 1061-1069) that aims to describe the relationship between reproductive health (determined by luteinizing hormone levels) and fiber consumption, we examine properties of SOLR estimators and compare them with other common approaches. PMID- 22086718 TI - Long-term follow-up of Barrett's epithelium: medical versus antireflux surgical therapy. AB - BACKGROUND: Barrett's esophagus (BE) is the most serious complication of GERD. In BE patients, this observational study compares the effects of antireflux surgery versus antisecretory medical therapy. METHODS: Overall, 89 BE patients (long BE = 45; short BE = 44) were considered: 45 patients underwent antireflux surgery and 44 underwent medical therapy. At both initial and follow-up endoscopy, symptoms were assessed using a detailed questionnaire; BE phenotypic changes [intestinal metaplasia (IM) presence/type, Cdx2 expression] were assessed by histology (H&E), histochemistry (HID), and immunohistochemistry. Surgical failures were defined as follows: (1) abnormal 24-h pH monitoring results after surgery, (2) endoscopically evident recurrent esophagitis, and (3) recurrent hiatal hernia or slipped fundoplication on endoscopy or barium swallow. RESULTS: Reversion of IM was observed in 12/44 SSBE and 0/45 LSBE patients (p < 0.01). Reversion was more frequently observed after effective antireflux surgery than after medical treatment (p = 0.04). In patients with no further evidence of IM after therapy, Cdx2 expression was also absent (p = 0.02). The extent of IM was reduced, and the IM phenotype improved in SSBE patients after surgery. CONCLUSIONS: Patients with short BE (but not those with long BE) may benefit from surgically reducing the esophagus' exposure to GE reflux; among these patients, successful surgery carries a higher IM reversion rate than medical treatment. PMID- 22086719 TI - Influence of chemical and structural properties of functionalized polythiophene based layers on electrochemical sensing of atrazine. AB - Sensitive layers based on conducting homopolymer [poly(3,4 ethylenedioxythiophene), denoted PEDOT] and copolymers [molecularly imprinted and non-imprinted poly(EDOT-co-3-thiophene acetic acid), denoted MICP and NICP, respectively] are electrosynthesized on gold substrates and used for the electrochemical detection of atrazine. These layers are characterized by cyclic voltammetry, ATR-FTIR spectroscopy, optical profilemetry, and AFM microscopy in order to study the effect of the chemical functionalities and of the structural properties of these conducting polymers on the physical chemistry of the interaction with atrazine targets and with the aim to improve the sensitivity of the recognition process. In particular, due to the presence in their backbones of preshaped functionalized cavities which keep the molecular memory of the targets, MICP layers show remarkable sensitivity, a low detection limit (10(-9) mol L( 1)), and a large linear range of detection (10(-8) to 10(-4) mol L(-1)), as demonstrated by square-wave voltammetry. PMID- 22086720 TI - Sirtuin 1 (SIRT1): the misunderstood HDAC. AB - The sirtuin family of NAD-dependent histone deacetylases (HDACs) consists of seven mammalian proteins, SIRT1-7. Many of the sirtuin isoforms also deacetylate nonhistone substrates, such as p53 (SIRT1) and alpha-tubulin (SIRT2). The sirtuin literature focuses on pharmacological activators of SIRT1 (e.g., resveratrol, SRT1720), proposed as therapeutics for diabetes, neurodegeneration, inflammation, and others. However, many of the SIRT1 activator results may have been due to artifacts in the assay methodology (i.e., use of fluorescently tagged substrates). A biological role for SIRT1 in cancer has been given less scrutiny but is no less equivocal. Although proposed initially as an oncogene, we present herein compelling data suggesting that SIRT1 is indeed a context-specific tumor suppressor. For oncology, SIRT1 inhibitors (dual SIRT1/2) are indicated as potential therapeutics. A number of sirtuin inhibitors have been developed but with mixed results in cellular systems and animal models. It is unclear whether this has been due to poorly understood model systems, signalling redundancy, and/or inadequately potent and selective tool compounds. This review provides an overview of recent developments in the field of SIRT1 function. While focusing on oncology, it aims to shed light on new concepts of expanding the selectivity spectrum, including other sirtuins such as SIRT2. PMID- 22086721 TI - A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs. AB - G-protein-coupled receptors (GPCRs) are pivotal in cellular responses to the environment and are common drug targets. Identification of selective small molecules acting on single GPCRs is complicated by the shared machinery coupling signal transduction to physiology. Here, we demonstrate a high-content screen using a panel of GPCR assays to identify receptor selective molecules acting within the kinase/phosphatase inhibitor family. A collection of 88 kinase and phosphatase inhibitors was screened against seven agonist-induced GPCR internalization cell models as well as transferrin uptake in human embryonic kidney cells. Molecules acting on a single receptor were identified through excluding pan-specific compounds affecting housekeeping endocytosis or disrupting internalization of multiple receptors. We identified compounds acting on a sole GPCR from activities in a broad range of chemical structures that could not be easily sorted by conventional means. Selective analysis can therefore rapidly select compounds selectively affecting GPCR activity with specificity to one receptor class through high-content screening. PMID- 22086722 TI - Screening, identification, and characterization of mechanistically diverse inhibitors of the Mycobacterium tuberculosis enzyme, pantothenate kinase (CoaA). AB - The authors describe the discovery of anti-mycobacterial compounds through identifying mechanistically diverse inhibitors of the essential Mycobacterium tuberculosis (Mtb) enzyme, pantothenate kinase (CoaA). Target-driven drug discovery technologies often work with purified enzymes, and inhibitors thus discovered may not optimally inhibit the form of the target enzyme predominant in the bacterial cell or may not be available at the desired concentration. Therefore, in addition to addressing entry or efflux issues, inhibitors with diverse mechanisms of inhibition (MoI) could be prioritized before hit-to-lead optimization. The authors describe a high-throughput assay based on protein thermal melting to screen large numbers of compounds for hits with diverse MoI. Following high-throughput screening for Mtb CoaA enzyme inhibitors, a concentration-dependent increase in protein thermal stability was used to identify true binders, and the degree of enhancement or reduction in thermal stability in the presence of substrate was used to classify inhibitors as competitive or non/uncompetitive. The thermal shift-based MoI assay could be adapted to screen hundreds of compounds in a single experiment as compared to traditional biochemical approaches for MoI determination. This MoI was confirmed through mechanistic studies that estimated K(ie) and K(ies) for representative compounds and through nuclear magnetic resonance-based ligand displacement assays. PMID- 22086723 TI - A cell-based high-throughput screening assay to measure cellular histone h3 lys27 trimethylation with a modified dissociation-enhanced lanthanide fluorescent immunoassay. AB - Histone proteins are subject to several modifications, including phosphorylation, acetylation, methylation, sumoylation, and ubiquitination. These posttranslational modifications play critical roles in chromatin structure and gene transcription. Because of their involvement in the progression of a variety of diseases, histone modifications are attracting increased attention. We report herein a high-throughput DELFIA assay to quantify H3K27me3 in the prostate cancer cell line, PC3. Using a high binding MaxiSorp plate, we were able to eliminate the need for the capture antibody. We also developed an effective method, a combination of "freeze-thaw" and 0.2 N HCl, to extract histone proteins in PC3 cells cultured in a 384-well plate. To compensate for cell viability change, we normalized H3K27me3 signal to the total amount of H3 in each sample well. As a result, we show that the assay has a good dynamic range with a robust assay window. Using a methlytransferase inhibitor, DZNep, we show that the change of H3K27me3 signal is target specific. This method simplifies the logistics in screening and profiling and reduces the cost per well to an acceptable level for high-throughput screening. The findings presented here should be applicable to other assays involving binding and extraction of histone proteins. PMID- 22086724 TI - Common seed analysis to identify off-target effects in siRNA screens. AB - Genome-scale small interfering RNA (siRNA) screens have become an increasingly popular approach to new target identification and pathway elucidation. However, the large data sets generated from siRNA screens have demonstrated high false positive rates and the requirement for extensive experimental triage to distinguish true hits. A number of groups have independently reported the presence of siRNAs with identical seed sequences among their top screening hits. Based on these observations, we have developed a comprehensive technique for detecting and visualizing seed-based off-target effects in siRNA screening data. This is accomplished by analyzing the behavior of siRNAs that share identical seed sequences, which we refer to as common seed analysis (CSA). By applying these techniques to primary screening data of the Wnt pathway, we identify 158 distinct seed sequences that have a statistically significant effect on the assay. The promiscuous seed sequences identified in this manner can then be discounted in the analysis of follow-up experiments using single siRNAs. The ability to detect off-target effects when sufficient numbers of siRNAs share a common seed has significant implications for the design of siRNA screening experiments, data analysis, hit selection, and library design. PMID- 22086725 TI - An efficient high-throughput screening method for MYST family acetyltransferases, a new class of epigenetic drug targets. AB - Epigenetic aberrations are increasingly regarded as key factors in cancer progression. Recently, deregulation of histone acetyltransferases (HATs) has been linked to several types of cancer. Monocytic leukemia zinc finger protein (MOZ) is a member of the MYST family of HATs, which regulate gene expression in cell proliferation and differentiation. Deregulation of these processes through constitutively active MOZ fusion proteins gives rise to the formation of leukemic stem cells, rendering MOZ an excellent target for treating myeloid leukemia. The authors implemented a hit discovery campaign to identify small-molecule inhibitors of MOZ-HAT activity. They developed a robust, homogeneous assay measuring the acetylation of synthetic histone peptides. In a primary screening campaign testing 243 000 lead-like compounds, they identified inhibitors from several chemical classes. Secondary assays were used to eliminate assay interfering compounds and prioritize confirmed hits. This study establishes a new high-throughput assay for HAT activity and could provide the foundation for the development of a new class of drugs for the treatment of leukemias. PMID- 22086726 TI - Primary and secondary drug screening assays for Friedreich ataxia. AB - Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardiodegenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the protein frataxin. Frataxin chaperones iron in the mitochondrial matrix for the assembly of iron-sulfur clusters (ISCs), which are prosthetic groups critical for the function of the Krebs cycle and the mitochondrial electron transport chain (ETC). Decreased expression of frataxin or the yeast frataxin orthologue, Yfh1p, is associated with decreased ISC assembly, mitochondrial iron accumulation, and increased oxidative stress, all of which contribute to mitochondrial dysfunction. Using yeast depleted of Yfh1p, a high throughput screening (HTS) assay was developed in which mitochondrial function was monitored by reduction of the tetrazolium dye WST-1 in a growth medium with a respiration-only carbon source. Of 101 200 compounds screened, 302 were identified that effectively rescue mitochondrial function. To confirm activities in mammalian cells and begin understanding mechanisms of action, secondary screening assays were developed using murine C2C12 cells and yeast mutants lacking specific complexes of the ETC, respectively. The compounds identified in this study have potential relevance for other neurodegenerative disorders associated with mitochondrial dysfunction, such as Parkinson disease. PMID- 22086727 TI - Phosphorescent mesomorphic dyads based on tetraacetylethane complexes of iridium(III). PMID- 22086728 TI - Promoting cancer screening within the patient centered medical home. AB - While consensus has grown that primary care is the essential access point in a high-performing health care system, the current model of primary care underperforms in both chronic disease management and prevention. The Patient Centered Medical Home model (PCMH) is at the center of efforts to reinvent primary care practice, and is regarded as the most promising approach to addressing the burden of chronic disease, improving health outcomes, and reducing health spending. However, the potential for the medical home to improve the delivery of cancer screening (and preventive services in general) has received limited attention in both conceptualization and practice. Medical home demonstrations to date have included few evidence-based preventive services in their outcome measures, and few have evaluated the effect of different payment models. Decreasing use of hospitals and emergency rooms and an emphasis on improving chronic care represent improvements in effective delivery of healthcare, but leave opportunities for reducing the burden of cancer untouched. Data confirm that what does or does not happen in the primary care setting has a substantial impact on cancer outcomes. Insofar as cancer is the leading cause of death before age 80, the PCMH model must prioritize adherence to cancer screening according to recommended guidelines, and systems, financial incentives, and reimbursements must be aligned to achieve that goal. This article explores capacities that are needed in the medical home model to facilitate the integration of cancer screening and other preventive services. These capacities include improved patient access and communication, health risk assessments, periodic preventive health exams, use of registries that store cancer risk information and screening history, ability to track and follow up on tests and referrals, feedback on performance, and payment models that reward cancer screening. PMID- 22086730 TI - Boiling peanut Ara h 1 results in the formation of aggregates with reduced allergenicity. AB - SCOPE: Roasting rather than boiling and Maillard modifications may modulate peanut allergenicity. We investigated how these factors affect the allergenic properties of a major peanut allergen, Ara h 1. METHODS AND RESULTS: Ara h 1 was purified from either raw (N-Ara h 1) or roasted (R-Ara h 1) peanuts. Boiling (100 degrees C 15 min; H-Ara h 1) resulted in a partial loss of Ara h 1 secondary structure and formation of rod-like branched aggregates with reduced IgE-binding capacity and impaired ability to induce mediator release. Glycated Ara h 1 (G-Ara h 1) formed by boiling in the presence of glucose behaved similarly. However, H- and G-Ara h1 retained the T-cell reactivity of N-Ara h 1. R-Ara h 1 was denatured, comprised compact, globular aggregates, and showed no evidence of glycation but retained the IgE-binding capacity of the native protein. CONCLUSION: Ara h 1 aggregates formed by boiling were morphologically distinct from those formed by roasting and had lower allergenic activity. Glycation had no additional effect on Ara h 1 allergenicity compared with heating alone. Taken together with published data on the loss of Ara h 2/6 from boiled peanuts, this supports the hypothesis that boiling reduces the allergenicity of peanuts. PMID- 22086731 TI - Reply to: MRI resolution enhancement: how useful are shifted images obtained by changing the demodulation frequency? PMID- 22086733 TI - 14.1 T whole body MRI for detection of mesoangioblast stem cells in a murine model of Duchenne muscular dystrophy. AB - Noninvasive imaging procedures will be important for stem cell therapy for muscular dystrophy (MD). Mesoangioblasts regenerate muscle in animal models of muscular dystrophy. In this study, superparamagnetic iron oxide nanoparticles were used to visualize mesoangioblasts in vivo with MRI. Mesoangioblasts incorporated superparamagnetic iron oxide without transfection reagents, and cell differentiation was not negatively impacted. A custom-built radiofrequency coil with an adjustable field of view and 14.1 T magnet were used for whole-body MRI of mice. High-resolution images of mesoangioblasts in skeletal and cardiac muscle of Mdx mice were obtained following local delivery. Labeled cells were verified by Prussian blue staining and dystrophin expression, indicating that the wild type mesoangioblasts survived and differentiated in muscle. Iron-labeled cells were detected with MRI in vivo 6 months following intracardiac injection but were determined to be activated macrophages. Iron-labeled cells were not detected by MRI following systemic delivery but were present in skeletal and cardiac muscle, visualized by Prussian blue staining. Systemically delivered mesoangioblasts were detected in lungs by Prussian blue staining and DiI but not by MRI in our study. MRI may be useful for short-term tracking of mesoangioblasts delivered locally but not for long-term monitoring or detection after systemic delivery. PMID- 22086735 TI - Can ex vivo evaluation (testing) predict the sensitivity of CLL cells to therapy with purine analogs in conjunction with an alkylating agent? A comparison of in vivo and ex vivo responses to treatment. AB - Malfunctions in the regulation of apoptosis cause the accumulation of malignant, long-lived B CD19+/CD5+ cells in chronic lymphocytic leukemia (CLL). The primary goal in CLL therapy is to overcome resistance to apoptosis and efficiently trigger programmed cell death in leukemic cells. This study demonstrated that the in vivo responses of malignant cells from CLL patients after administration of purine analogs (cladribine/fludarabine) with cyclophosphamide vary significantly. For comparative purposes, the sensitivity of leukemic cells obtained from the same CLL patients to conventional purine analogs and the selective CDK inhibitor R-roscovitine (ROSC) was determined, with and without the addition of an alkylating agent, prior to the onset of in vivo therapy. The kinetics and rate of spontaneous and drug-induced apoptosis of CLL cells under ex vivo conditions differed significantly between patients, mirroring the variability observed during in vivo treatment. Interestingly, individual patients' leukemic cells were comparably sensitive to the drugs under both conditions. Of the drugs examined, ROSC exerted the highest therapeutic efficacy under ex vivo conditions. Our results indicate that ex vivo testing might be useful for identifying the most potent first-line therapeutic regimen for specific CLL patients and possibly for the design of therapies tailored for individual CLL patients. PMID- 22086736 TI - Prognostic significance of phosphorylated RON in esophageal squamous cell carcinoma. AB - Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer. RON is a transmembrane receptor overexpressed in various cancers; however, the clinical significance of its phosphorylated form (pRON) is not fully deciphered. This report is the first to investigate the expression and clinical significance of pRON in human ESCC. Quantitative polymerase chain reaction revealed an up-regulation of RON mRNA in 70% (7/10) of ESCC tissues when compared to the adjacent nontumor tissues. An overexpression of pRON protein was found in most of the ESCC cell lines studied (4/5) when compared to two non-neoplastic esophageal epithelial cells using immunoblot. In 64 ESCC tissues, pRON was localized at the cell membrane, cytoplasm and nucleus in 15 (23.4%), 63 (98.4%) and 61 (95.3%) cases using immunohistochemistry. Patients having high expression of cytoplasmic pRON significantly associated with shorter median survival when compared to those with low expression (25.41 months vs. 14.43 months), suggesting cytoplasmic pRON as a potential marker for poor prognosis in ESCC patients. PMID- 22086737 TI - Reduced expression of activin receptor-like kinase 7 in breast cancer is associated with tumor progression. AB - To explore the clinical implication of activin receptor-like kinase 7 (ALK7) expression in breast cancer, we evaluated its protein level in six kinds of human breast tissue samples, including adjacent normal tissues, adenosis, breast fibroadenoma, ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and lymph node metastases (LNM). Immunohistochemical analyses showed that ALK7 was more frequently and much more intensely expressed in adjacent normal tissues, adenosis, and fibroadenoma tissues than in malignant tissues (DCIS, IDC, and LNM). Furthermore, the ALK7 expression in primary tumors and the corresponding LNM was evaluated in parallel samples from 60 patients with IDC. Results showed that the ALK7 expression status in primary tumors and LNM was concordant in 53 patients (88%), suggesting that ALK7 expression was retained in LNM. Moreover, our results suggested that ALK7 expression inversely correlated with the tumor grade (P=0.009) and clinical stage (P=0.004) in IDC significantly. Finally, the effect of activin-ALK7 pathway on the breast cancer cell growth was elucidated, and results revealed that overexpression of ALK7 could restore the inhibitory effect of activin B on the growth of ALK7-negative breast cancer cell line, ZR-75 30. These findings provide the evidence that the reduction or lack of ALK7 expression may account for the loss of its ligand sensitivity of breast cancer cells, thereby leading to breast tumor progression. PMID- 22086738 TI - Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson's disease. AB - Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (TM) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real world activity. PMID- 22086739 TI - Integrating hospital information systems in healthcare institutions: a mediation architecture. AB - Many studies have examined the integration of information systems into healthcare institutions, leading to several standards in the healthcare domain (CORBAmed: Common Object Request Broker Architecture in Medicine; HL7: Health Level Seven International; DICOM: Digital Imaging and Communications in Medicine; and IHE: Integrating the Healthcare Enterprise). Due to the existence of a wide diversity of heterogeneous systems, three essential factors are necessary to fully integrate a system: data, functions and workflow. However, most of the previous studies have dealt with only one or two of these factors and this makes the system integration unsatisfactory. In this paper, we propose a flexible, scalable architecture for Hospital Information Systems (HIS). Our main purpose is to provide a practical solution to insure HIS interoperability so that healthcare institutions can communicate without being obliged to change their local information systems and without altering the tasks of the healthcare professionals. Our architecture is a mediation architecture with 3 levels: 1) a database level, 2) a middleware level and 3) a user interface level. The mediation is based on two central components: the Mediator and the Adapter. Using the XML format allows us to establish a structured, secured exchange of healthcare data. The notion of medical ontology is introduced to solve semantic conflicts and to unify the language used for the exchange. Our mediation architecture provides an effective, promising model that promotes the integration of hospital information systems that are autonomous, heterogeneous, semantically interoperable and platform-independent. PMID- 22086740 TI - Report of a case of steroid-induced psychosis and inappropriate sexual behaviour in an adolescent. AB - We present the case of an acute steroid-induced psychosis in a 17-year-old boy who presented with inappropriate sexual behaviour. Quetiapine treatment was initiated at an initial dosage of 300 mg/day. The dosage was increased to 900 mg/day on the fourth day of the treatment. The patient's symptoms began to improve in the second week and were resolved by the fourth week of quetiapine treatment. Steroid use may result in a psychosis, including inappropriate sexual behaviour. Clinicians should be very cautious while administering these drugs and should consider and monitor side effects carefully. PMID- 22086742 TI - Venlafaxin-associated post-ictal asystole during electroconvulsive therapy. AB - While post-stimulus asystoles occur quite often during electroconvulsive therapy (ECT) post-ictal or post-seizure sinus bradycardias or even asystoles are rare events. We report the case of an 82-year-old female patient with a current major depressive episode, who developed the rare event of a post-ictal asystole of 6 s and 4 ventricular escape beats during ECT. In the past this patient with a bipolar disorder and mild Alzheimer's disease had already been frequently treated with ECT with good success and no adverse events. Relevant comedication was venlafaxin, quetiapine, donepezil and clonidine, anesthesia was performed with ketamine and succinylcholine. Concurrent medication was completely unchanged compared to previous ECT sessions with the exception of venlafaxine, presumably at high serum levels. In summary, in line with some already existing reports, we expect the noradrenergic action of venlafaxin to have contributed substantially to the post-ictal asystole and want to indicate that the combination of ECT and venlafaxin might be harmful--especially in the elderly population. PMID- 22086741 TI - Coprescription of levodopa with antipsychotics in a population of 84,596 psychiatric inpatients from 1994 to 2008. AB - INTRODUCTION: Patients on levodopa therapy frequently require additional antipsychotic pharmacotherapy. However, consideration must be given to antagonistic interactions on dopamine receptors between levodopa and antipsychotics, and efficacy and safety of such combinations. We therefore aimed to explore the practice and rationale of coprescription between levodopa and antipsychotics in psychiatric patients. METHODS: A descriptive retrospective study based on cross-sectional prescription data repeatedly collected from psychiatric inpatients through the international Drug Safety in Psychiatry (AMSP) program between 1994 and 2008 was undertaken. RESULTS: Within a population of 84 596 psychiatric patients the prevalence of levodopa therapy was 1.0% (n=886). Among those patients on levodopa therapy 59.6% (n=528) also received antipsychotics. Quetiapine coprescription increased after its first marketing in 2000 to 45.9% in 2008. Coprescription of clozapine and olanzapine decreased from up to 25 and 22%, respectively, before to less than 10% after the introduction of quetiapine. Coprescribing of other antipsychotics remained approximately stable with average prevalences between 6 and less than 1%. DISCUSSION: Quetiapine has now replaced clozapine as the most frequently coprescribed neuroleptic in psychiatric patients with levodopa therapy. This is in accordance with recent data indicating a low potential for clinically relevant interactions with levodopa and efficacy against psychosis in levodopa-treated patients. The combined use of antipsychotics other than quetiapine and clozapine with levodopa is less common and generally not supported by appropriate evidence. PMID- 22086743 TI - Olanzapine-induced anaphylactic shock: a case report. AB - Olanzapine is a second-generation antipsychotic, which is also used as a mood stabilizer. We report a case of a 33-year-old psychiatric patient, with bipolar affective disorder, who developed anaphylaxis as a late reaction to olanzapine. This case report shows the possibility, although rare, of a severe late anaphylactic reaction to olanzapine. PMID- 22086744 TI - Therapeutic drug monitoring of children and adolescents treated with fluoxetine. AB - INTRODUCTION: Information about therapeutic serum levels of fluoxetine (FLX) and its major metabolite norfluoxetine (NORFLX) in children and adolescents is scarce. METHODS: Therapeutic drug monitoring (TDM) of FLX was routinely performed in 71 subjects treated for a major depressive disorder (MDD) (10-60 mg/d FLX, median: 20 mg/d). Correlations between serum concentration and dosage, age, gender, smoking habits and adverse events were analysed. RESULTS: Serum concentrations of the active moiety (FLX + NORFLX) ranged from 21 to 613 ng/mL (mean concentration of 213 +/- 118 ng/mL, median: 185 ng/mL). High inter individual variability in serum concentrations of the active moiety of FLX at each dosage level was observed and no relationship between serum concentration and clinical outcome was found. Apart from smoking, none of the factors tested had a significant eff ect on the serum concentration. DISCUSSION: It was shown that serum concentrations of the active moiety of FLX in children and adolescents seem to be similar to those in adults, with a high level of inter-individual variation. The proportion of patients who showed benefits from treatment with a dose of 20 mg/d FLX was high. PMID- 22086745 TI - Pregabalin: dose-response relationship in generalized anxiety disorder. AB - INTRODUCTION: Pregabalin is a structural analogue of the inhibitory neurotransmitter GABA. Although pregabalin has demonstrated efficacy in the treatment of generalized anxiety disorder (GAD) in a number of randomized controlled trials, there is little published data on the optimal dose for treating this condition. The objective of the current study was to examine the dose-response relationship for treatment of GAD with pregabalin. METHOD: The current study pools results from previous fixed-dose treatment trials of GAD with pregabalin and uses curve-fitting statistical procedures to generate curvilinear regression lines as a synthesis of previous dose-response information. RESULTS: Peak reduction in anxiety symptoms was observed to occur at a dose of approximately 450 mg/day, with a small reduction in treatment effect beyond this dose. Treatment effect on psychic anxiety symptoms reached a peak at approximately 400 mg, with a reduction in efficacy beyond this dose. Somatic anxiety symptoms showed continued increase in therapeutic effect up to the maximum dose of 600 mg/day. DISCUSSION: Implications for psychiatric practice, limitations of the methodology and avenues for future research are discussed. PMID- 22086746 TI - Does pain improve earlier than mood in depressed patients with painful physical symptoms treated with duloxetine? AB - INTRODUCTION: In depressed patients tricyclic antidepressants and selective serotonin and noradrenaline reuptake inhibitors can reduce not only depressive, but also painful physical symptoms. We investigated whether under treatment with duloxetine pain improves earlier than mood. METHODS: Data were obtained within a prospective 6-month multi-centre naturalistic study in adult out-patients with depressive episodes treated with duloxetine (fl exible doses: 30-120 mg/day). Pain and mood were assessed daily by visual analogue scales. For responders (n = 622) "time to 50 % pain response" and "time to 50 % mood response" were determined by counting the earliest day between day 0 and 27, at which the patient achieved 50 % improvement. RESULTS: Mean time to 50 % pain response (mean 6.3 days, SD 5.3) was significantly shorter than time to 50 % mood response (mean 7.6 days, SD 6.0, mean difference 1.3 days, SD 6.4; p < 0.0001). DISCUSSION: In duloxetine-responders to both pain and mood, self-rated pain improved slightly earlier than self-rated mood. The short temporal dissociation between pain and mood improvement might be explained by an earlier conscious perception of pain than mood changes. PMID- 22086747 TI - Efficacy and tolerability of a once daily formulation of Ginkgo biloba extract EGb 761(r) in Alzheimer's disease and vascular dementia: results from a randomised controlled trial. AB - INTRODUCTION: A 24-week randomised controlled trial was conducted to assess the efficacy of a 240 mg once-daily preparation of Ginkgo biloba extract EGb 761(r) in 404 outpatients >= 50 years diagnosed with mild to moderate dementia (SKT 9 23), Alzheimer's disease (AD) or vascular dementia (VaD), with neuropsychiatric features (NPI total score >= 5). METHODS: Separate analyses were performed for diagnostic subgroups (probable or possible AD; VaD). RESULTS: 333 patients were diagnosed with AD and 71 with VaD. EGb 761(r) treatment was superior to placebo with respect to the SKT total score (drug-placebo differences: 1.7 for AD, p<0.001, and 1.4 for VaD, p<0.05) and the NPI total score (drug-placebo differences: 3.1 for AD, p<0.001 and 3.2 for VaD, p<0.05). Significant drug placebo differences were found for most secondary outcome variables with no major differences between AD and VaD subgroups. Rates of adverse events in EGb 761(r) and placebo groups were essentially similar. CONCLUSION: EGb 761(r) improved cognitive functioning, neuropsychiatric symptoms and functional abilities in both types of dementia. PMID- 22086748 TI - The serotonin transporter promoter polymorphism (5-HTTLPR) affects the relation between antidepressant serum concentrations and effectiveness in major depression. AB - INTRODUCTION: Both the serotonin transporter promotor polymorphism (5-HTTLPR) and serum concentrations of SSRIs have been shown to affect response to SSRIs. Results, however, are inconsistent. The aim of this study was to investigate whether remission or response to SSRIs is influenced by an interaction of 5 HTTLPR and SSRI serum concentrations. METHODS: 49 patients with major depression and SSRI treatment were genotyped for the 5-HTTLPR locus including the rs25531. Drug serum concentrations and depression severity were measured weekly. RESULTS: Logistic regression analysis revealed a significant association between 5-HTTLPR, SSRI serum concentrations and response to treatment. A favourable treatment outcome correlated with SSRI serum concentration in 5-HTTLPR-L(A) allele carriers (r2 = 34.3 %; p = 0.001), but not in S/L(G)-allele carriers (p = 0.31). DISCUSSION: In the group of L(A) allele carriers, those MDD patients with a high antidepressant serum concentrations responded better to treatment than patients with a low serum concentration. We conclude that the 5-HTTLPR might affect reponse to SRRI subject to serum concentrations. If replicated this might be a starting point for prospective clinical trials. PMID- 22086749 TI - Risperidone and olanzapine versus another first generation antipsychotic in patients with schizophrenia inadequately responsive to first generation antipsychotics. AB - OBJECTIVE: This study compares the efficacy of risperidone and olanzapine to that of first-generation antipsychotics (FGAs) in patients with schizophrenia, who failed to show a response to initial trials of FGAs. METHOD: This study was an 8 week treatment, randomized, rater-blind, active-control study with 3 treatment arms. 48 patients, who showed inadequate response to 1 FGA, were enrolled and randomized into risperidone, olanzapine, or FGA (haloperidol or trifluoperazine) groups. They were blindly assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale-Severity, and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and biweekly. RESULTS: All 3 groups demonstrated a significant decrease in the PANSS total, positive, and general scores from baseline to endpoint (p-values range from 0.003 to 0.021). There were no significant differences among the 3 groups in score changes. The olanzapine group had significant score reductions than the risperidone and FGAs groups in terms of the ESRS subjective total score and did not experience a significant increase in the dose of anticholinergics. The FGA group demonstrated that extrapyramidal syndrome (EPS) worsened under an increased dosage of anti-EPS drugs. Olanzapine was associated with significant body weight gain (2.69 +/- 4.0 kg, p=0.026), but there were no significant group differences on weight gain. CONCLUSIONS: Haloperidol or trifluoperazine demonstrated similar efficacy as risperidone or olanzapine for patients with schizophrenia who had failed their first trial with a FGA. Related double-blind, fixed dose studies with a larger sample size are needed to confirm the results of our study. PMID- 22086750 TI - Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history-adjusted marginal structural models. AB - Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is therefore highly dynamic. In 1992-1996, the Nordic Society of Paediatric Haematology and Oncology (NOPHO) conducted a randomised study (NOPHO-ALL-92) to investigate the effect of a new and more sophisticated dynamic treatment strategy. Unexpectedly, the new strategy worsened the outcome for the girls, whereas there were no treatment differences for the boys. There are as yet no general guidelines for optimising the treatment. On basis of the data from this study, our goal is to formulate an alternative dosing strategy. We use recently developed methods proposed by van der Laan et al. to obtain statistical models that may be used in the guidance of how the physicians should assign the doses to the patients to obtain the target of the treatment. We present a possible strategy and discuss the reliability of this strategy. The implementation is complicated, and we touch upon the limitations of the methods in relation to the formulation of alternative dosing strategies for the maintenance therapy. PMID- 22086751 TI - Stearylated INF7 peptide enhances endosomal escape and gene expression of PEGylated nanoparticles both in vitro and in vivo. AB - We previously reported on a stearylated INF7 peptide (str-INF7), which enhances the endosomal escape of an octaarginine (R8)-modified liposomal particle encapsulating plasmid DNA (pDNA) in a fusion-independent manner. This study examined whether this peptide derivative enhanced the endosomal escape and gene expression of PEGylated liposomes encapsulating pDNA. We used a PEGylated, R8 modified multifunctional envelope-type nanodevice (R8-MEND) as a model for PEGylated liposomes. Polyethylene glycol 2000 (PEG2000) attached to two different anchors, distearoylphosphatidylethanolamine (DSPE-PEG) or dimyristoylphosphatidylethanolamine (DMPE-PEG), was used to modify the R8-MEND in the presence or absence of two different concentrations of str-INF7. Modification of the PEGylated R8-MEND with str-INF7 resulted in luciferase gene expression levels in HeLa cells that were 73-fold and 24-fold higher than the corresponding value for an unmodified MEND in the case of DSPE-PEG and DMPE-PEG, respectively. The endosomal escape of the PEGylated R8-MEND was improved by str-INF7, as confirmed by confocal laser scanning microscopy. Furthermore, modification with str-INF7 enhanced the hepatic gene expression of the R8-MEND modified with DSPE PEG and DMPE-PEG by 95-fold and 1885-fold, respectively, after intravenous injection in mice. Collectively, these data demonstrate that str-INF7 can be a useful device for enhancing the endosomal escape even for PEGylated liposomes encapsulating pDNA. PMID- 22086752 TI - Providing cancer care: individual or team sport? PMID- 22086753 TI - From the editors' desk: realizing the dream: mentorship in academic medicine. PMID- 22086754 TI - Older homeless adults: can we do more? PMID- 22086755 TI - Arago's best paper. AB - The year 2011 is the bicentennial of Francois Arago's discovery of optical rotation. The immediate usurpation of the study of optical activity by Jean Baptiste Biot led to the first well-known judgments of the arrangements of atoms in space. Scientists are less aware that Arago achieved something far greater than his contributions to optics, by signing the 1848 decree that abolished slavery throughout the French Empire. Opposing attitudes of Arago and Biot toward abolition, foreshadowed in their early rift over optical rotation, were surprisingly exposed in mid-century developments in chiroptics. As shown in a recent book by Levitt, Arago sought a reinvention of the whole colonial plantation system consistent with Republican principles, while Biot tried to place the cane sugar industry and slave-based economy on the quantitative foundation of saccharimetry. A reevaluation of the circumstances of abolition can celebrate both societal evolution and optical rotation on the 200th birthday of the latter. Episodes from Arago's life that arguably created his predisposition toward abolition are emphasized: He was imprisoned several times as a young man and knew the loss of liberty, his brother Jacques witnessed slavery in Brazil and advocated abolition in travel books prepared with Francois, and finally, in writing the biography of the Marquis de Condorcet, the spirit behind the first, albeit impermanent French abolition of slavery in 1794, Arago found proof of concept for his comparable challenge. Curiously, the measurement of the optical rotation of crystals and sugar, the foci of Arago and Biot, respectively, remain among the greatest challenges in polarimetry. Current developments are reviewed with respect to chiroptical anisotropy and in vivo glucose detection driven by the pandemic of diabetes, a disease diagnosed polarimetrically by Biot that claimed the life of Arago. PMID- 22086756 TI - One-pot synthesis of isoquinolinium salts by rhodium-catalyzed C-H bond activation: application to the total synthesis of oxychelerythrine. PMID- 22086757 TI - Safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania: a 12-week open-label study. AB - OBJECTIVE: To examine the safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania. METHOD: Subjects (n = 18) who were acutely manic, did not respond to lithium, anticonvulsants, and neuroleptics, and/or had intolerable side effects to them in previous manic episodes were openly treated with olanzapine monotherapy (5-40 mg/d) for 12 weeks. The primary and secondary outcomes included the change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score, Clinical Global Impression for Bipolar Disorder Severity Scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D) and Positive and Negative Syndrome Scale (PANSS), and response and remission rate. RESULTS: The mean change in YMRS total score from baseline to endpoint was -23.3 +/- 8.4 (p < 0.001). Fifteen (88.5%) patients achieved response (>=50% reduction in YMRS total score) and 14 (77.8%) achieved remission (YMRS total score <=9 at endpoint). Mean changes from baseline to endpoint in CGI-S for mania and PANSS total score were significant, but not the changes in HAM-D total score or CGI-S for depression. The most common adverse events were sedation, self-reported weight gain, >=7% increase in body weight, dizziness, and akathisia. CONCLUSIONS: These preliminary results suggest that olanzapine monotherapy is effective and relatively safe in patients with treatment-resistant bipolar mania. Randomized, double-blind, placebo-controlled study is warranted. PMID- 22086758 TI - The protective role of natural phytoalexin resveratrol on inflammation, fibrosis and regeneration in cholestatic liver injury. AB - Liver injuries can trigger a cascade of inflammatory responses and as a result, initiate the process of hepatic regeneration and fibrogenesis. Resveratrol (RSV) has multiple health-promoting benefits. This study evaluated the potential protective effects and mechanism of RSV as related to cholestatic liver injury. RSV was given (4 mg/kg/day, i.p.) for either 3 days or 7 days after bile duct ligation (BDL) injury. RSV significantly reduced serum ALT, AST but not T-bil on Day 3. At this early stage of injury, RSV significantly reduced TNF-alpha and IL 6 mRNA and decreased the number of Kupffer cells (CD68(+) ) recruited in the injured liver. RSV decreased hepatic fibrosis and reduced collagen Ialpha1 and TIMP-1 mRNA on Day 7. At the later stages of injury, RSV increased the number of Ki67(+) hepatocytes indicating that RSV promoted hepatocyte proliferation. Additionally, it resulted in decreased expression of 4-hydroxynonenal and increased expression of the hepatocyte growth factor protein and mRNA in the RSV treated BDL group. Meanwhile, RSV reduced the mortality rate of BDL mice. In conclusion, RSV attenuated inflammation and reduced Kupffer cells activation. RSV decreased fibrosis and promoted hepatocyte regeneration, which increased the survival of BDL mice. RSV was beneficial for the treatment of cholestatic liver injury. PMID- 22086759 TI - Morphologic and functional association of retinal layers beneath the epiretinal membrane with spectral-domain optical coherence tomography in eyes without photoreceptor abnormality. AB - PURPOSE: To access the differential thickening of retinal layers in the epiretinal membrane (ERM) and to determine their correlation with visual acuity. METHODS: Prospective and comparative case series of 22 patients, each of whom has one unilateral ERM eye and one normal eye. The eyes with abnormal photoreceptor layer by OCT images were excluded. Spectral-domain optical coherence tomography (SD-OCT) images were generated with Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). The thicknesses were obtained by a volume scan program using manual segmentation of the total retina, inner retina, inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL) in the fovea (1.0 mm diameter) and the parafovea (3.0 mm diameter). The thickness and the proportion of each retinal layer and their relationship with visual acuity were analyzed. RESULTS: All retinal layers of ERM eyes were thicker than the patients' normal eyes (P < 0.05). In the fovea, the levels of thickness difference of inner retina (240.38%) and INL (266.26%) were significantly higher than total retina (126.7%). Visual acuity was not correlated with the retinal thickness in both ERM eyes and normal eyes (P > 0.05). However, significant correlations between visual acuity difference with retinal thickness difference were found in the total retina (rho = 0.450, P = 0.046) and the inner retina (rho = 0.602, P = 0.005) of the fovea, as well as in the inner retina (rho = 0.468, P = 0.037) and the INL (rho = 0.466, P = 0.039) of the parafovea. When we convert each retinal thickness into a proportion, in the foveal area, the percentages of thickness of the inner retina and the INL of ERM eye were significantly higher than that of the normal eye (P < 0.05), whereas that of the ONL was significantly lower (P < 0.05). In the parafoveal area, the percentage of thickness of the inner retina of the ERM eye was significantly higher than that of the normal eye (P < 0.05), whereas that of ONL was significantly lower (P < 0.05). CONCLUSIONS: Idiopathic ERM affects the volume of all retinal layers. Inner retina had the most variability of thickness and is strongly associated with visual acuity changes in the case of intact photoreceptor layer. PMID- 22086761 TI - A latent class method for the selection of prototypes using expert ratings. AB - Latent class analysis can be applied to the outcomes of expert ratings to select objects or subjects that are regarded as prototypical of a category in an ordinal classification system. During a pilot study, Monte Carlo simulations demonstrated that the probability of correct selection is larger when using latent class analysis than when using methods that rely on agreement statistics. Further improvements in the latent class results can also be achieved by applying affine transformations to latent class estimates of sensitivity and specificity. An application is presented that involves the selection of prototypical radiographs. PMID- 22086760 TI - Effect of lipophilicity on the bioavailability of drugs after percutaneous administration by dissolving microneedles. AB - To elucidate drug lipophilicity effects on the bioavailability (BA) of drugs from skin after administration by dissolving microneedles, nine compounds with different lipophilicity indexes (log p value) were formulated into two-layered dissolving microneedles and administered percutaneously to rat skin: desmopressin (DDAVP), sumatriptan (ST), fluorescein (FL), granisetron (GRN), pindolol (PDL), pravastatin (PRV), rhodamine 123 (Rho), rifampicin (RFP), and salmeterol (SLM). Plasma drug concentrations were measured using liquid chromatography-tandem mass spectrometry and spectrofluorometry. In vivo dissolution and diffusion in both horizontal and vertical directions of FL and RH in the skin were studied using fluorescence microscopy. Respective BAs were 95.1 +/- 7.9% (DDAVP), 84.2 +/- 2.7% (ST), 82.3 +/- 7.2% (FL), 82.7 +/- 6.7% (GRN), 71.6 +/- 3.8% (PDL), 63.6 +/- 7.5% (PRV), 53.7 +/- 8.3% (Rho), 46.2 +/- 6.1% (RFP), and 38.4 +/- 2.7% (SM). BA decreased as the lipophilicity index, log p value, of the drug increased from 1.95 to 1.73. The respective remaining percentages in skin tissue were 1.4 +/- 0.7% (DDAVP), 0.9 +/- 0.1% (ST), 1.0 +/- 0.2% (FL), 3.4 +/- 1.2% (GRN), 14.5 +/- 3.7% (PDL), 23.4 +/- 5.2% (PRV), 32.2 +/- 6.0% (Rho), 40.7 +/- 4.9% (RFP), and 40.6 +/- 5.1% (SLM), dependent on log p. Fluorescence microscopy showed no FL or Rho in skin tissue within 4 and 24 h after administration, respectively. The BA of drugs delivered by dissolving microneedles depends on the drug solubility in the skin epidermis and dermis. PMID- 22086762 TI - [Modeling employee stress in psychiatric rehabilitation--effects of personal and organizational factors]. AB - Increasing stress-associated health problems in Germany often are attributed to problems on the job, in particular to rising work demands. The study includes several stress predictors from other results and from literature in one predictive model for the field of work of "psychiatric rehabilitation".A cross sectional design was used to measure personal and organizational variables with quantitative standard questionnaires as self-ratings from n=243 pedagogically active employees from various professions. Overall stress and job stress were measured with different instruments.The sample showed above-average overall stress scores along with below-average job stress scores. The multivariate predictive model for explaining the heightened stress shows pathogenetic and salutogenetic main effects for organizational variables such as "gratification crisis" and personal variables such as "occupational self-efficacy expectations" as well as an interaction of both types of variables. There are relevant gender specific results concerning empathy and differences between professions concerning the extent of occupational self-efficacy.The results are a matter of particular interest for the practice of workplace health promotion as well as for social work schools, the main group in our sample being social workers. PMID- 22086763 TI - Rhodiola rosea extract protects human cortical neurons against glutamate and hydrogen peroxide-induced cell death through reduction in the accumulation of intracellular calcium. AB - The aim of this study was to investigate the neuroprotective effects of a titolated extract from Rhodiola rosea L. (RrE) and of salidroside (Sa), one of the major biologically active compounds extracted from this medicinal plant, against oxidative stressor hydrogen peroxide (H2O2) and glutamate (GLU)-induced cell apoptosis in a human cortical cell line (HCN 1-A) maintained in culture. The results obtained indicate that exposure of differentiated HCN 1-A neurons to GLU or H2O2 resulted in concentration-dependent cell death. A 24 h pre-treatment with RrE significantly increased cell survival and significantly prevented the plasma membrane damage and the morphological disruption caused by GLU or H2O2, indicating that neurons treated with RrE were protected from the neurotoxicity induced by the oxidative stressor used. In addition, RrE significantly reduced H2O2 or GLU-induced elevation of intracellular free Ca2+ concentration. The results obtained have also shown that Sa caused similar effects in all experimental models used; however, the potency of the action was lower than that of the extract containing corresponding quantities of Sa. These findings indicate that RrE has a neuroprotective effect in cortical neurons and suggest that the antioxidant activity of the RrE, due to the structural features of the synergic active principles they contain, may be responsible for its ability to stabilize cellular Ca2+ homeostasis. PMID- 22086764 TI - Optical modulation and selective recovery of Cy5 fluorescence. AB - Fluorescence modulation offers the opportunity to detect low-concentration fluorophore signals within high background. Applicable from the single-molecule to bulk levels, we demonstrate long-wavelength optical depopulation of dark states that otherwise limit Cy5 fluorescence intensity. By modulated excitation of a long-wavelength Cy5 transient absorption, we dynamically modulate Cy5 emission. The frequency dependence enables specification of the dark-state timescales enabling optical-demodulation-based signal recovery from high background. These dual-laser illumination schemes for high-sensitivity fluorescence-signal recovery easily improve signal-to-noise ratios by well over an order of magnitude, largely by discrimination against background. Previously limited to very specialized dyes, our utilization of long-lived dark states in Cy5 enables selective detection of this very common single-molecule and bulk fluorophore. Although, in principle, the "dark state" can arise from any photoinduced process, we demonstrate that cis-trans photoisomerization, with its unique transient absorption and lifetime enables this sensitivity boosting, long wavelength modulation to occur in Cy5. Such studies underscore the need for transient absorption studies on common fluorophores to extend the impact of fluorescence modulation for high-sensitivity fluorescence imaging in a much wider array of applications. PMID- 22086765 TI - Structural dynamics of free amino acids in diffraction. PMID- 22086766 TI - Prolonged impact of chemotherapy on fatigue in breast cancer survivors: a longitudinal comparison with radiotherapy-treated breast cancer survivors and noncancer controls. AB - BACKGROUND: In this study, the authors examined the influence of prior treatment on the course of fatigue in breast cancer survivors. Patients who received chemotherapy were expected to have greater fatigue than patients who received radiotherapy and noncancer controls 6 months after the completion of treatment, but they were expected to recover to levels similar to those of the other 2 groups 3 years later. METHODS: Patients with stage 0 through II breast cancer completed the Fatigue Symptom Inventory (FSI) and the Profile of Mood States Fatigue Scale (POMS-FAT) 6 months (T1) and 42 months (T2) after completing chemotherapy with or without radiotherapy (the CT group; n = 103) or radiotherapy only (the RT group; n = 102). An age-matched group of women with no history of cancer (the NC group; n = 193) was assessed over a similar interval. RESULTS: A significant (P = .041) group * time effect for FSI severity scores revealed that fatigue worsened over time in the CT group but remained stable and lower in the RT and NC groups. There also were significant group effects for FSI days (P < .001) and POMS-FAT (P = .010) scores, indicating that fatigue was significantly greater across time in the CT group than in the NC group (POMS-FAT) or the RT and NC groups (FSI days). CONCLUSIONS: Contrary to expectations, fatigue did not diminish over time in patients with breast cancer who received chemotherapy. This finding has important implications for patient education and for fatigue monitoring during follow-up. The authors concluded that future research should seek to examine possible mechanisms to explain the apparent prolonged impact of chemotherapy on fatigue in breast cancer survivors. PMID- 22086767 TI - Predicting nucleic acid binding interfaces from structural models of proteins. AB - The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However, the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three-dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared with patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure. PMID- 22086768 TI - Coordinate-based colocalization analysis of single-molecule localization microscopy data. AB - Colocalization of differently labeled biomolecules is a valuable tool in fluorescence microscopy and can provide information on biomolecular interactions. With the advent of super-resolution microscopy, colocalization analysis is getting closer to molecular resolution, bridging the gap to other technologies such as fluorescence resonance energy transfer. Among these novel microscopic techniques, single-molecule localization-based super-resolution methods offer the advantage of providing single-molecule coordinates that, rather than intensity information, can be used for colocalization analysis. This requires adapting the existing mathematical algorithms for localization microscopy data. Here, we introduce an algorithm for coordinate-based colocalization analysis which is suited for single-molecule super-resolution data. In addition, we present an experimental configuration for simultaneous dual-color imaging together with a robust approach to correct for optical aberrations with an accuracy of a few nanometers. We demonstrate the potential of our approach for cellular structures and for two proteins binding actin filaments. PMID- 22086769 TI - Complications in endoscopic sinus surgery for chronic rhinosinusitis: a 25-year experience. AB - OBJECTIVES/HYPOTHESIS: The aim of this study was to review complications occurring as a result of endoscopic sinus surgery by one surgeon in an academic practice during a 25-year period. STUDY DESIGN: Retrospective clinical study. METHODS: A register of complications was tabulated during a period of 25 years for endoscopic sinus surgery performed for chronic rhinosinusitis in 3,402 patients (6,148 sides). All complications were reviewed as a whole and were not divided into major or minor categories. RESULTS: A total of 105 patients were found to have complicated endoscopic sinus surgery, for an overall patient complication rate of 0.031, or 0.017 per operated side. The most common complications were hemorrhage (n = 41), orbital complications (n = 29), and CSF leak (n = 19). The following factors were noted to have increased risk for complications: age, revision surgery, nasal polyps, anatomic variation, extensive disease, overall health, medications, and underlying factors. Certain types of instrumentation such as powered instrumentation placed patients at greater risk. The use of image guidance or surgical experience did not eliminate complications from occurring. CONCLUSIONS: Complications of endoscopic sinus surgery still occur 25 years after the initial introduction of the surgery in 1985. Many complications can be managed without a bad outcome. The key to prevention is knowledge of anatomy, preparation, anticipation, and experience. Even then, complications can occur in the most experienced hands. Patients most at risk for complications include those with revision surgery, extensive disease, skull base anatomic or radiologic variations or dehiscences related to disease or previous surgery, and the use of powered instrumentation. PMID- 22086770 TI - Two-dimensional LC-MS fractioning and cross-matching of mass spectrometric data for rational identification of bioactive compounds in crude extracts. AB - Bioprospecting aims at the identification of biological compounds with novel properties. Identification of such compounds in crude complex biological extracts is a comprehensive challenge. As a large number of extracts must be screened for successful identification of one potential promising lead, rational screening strategies must be developed. Here we report on a novel two stage rational LC-MS strategy of extracts already pre-screened and proven to contain bioactive compound(s). All extracts are initially fractionated using one and the same LC condition with parallel mass spectrometric detection. Fractions containing bioactive compound(s) are then subjected to a second fractional stage using two different chromatographic conditions. Mass detection is also included at this stage, and a cross-matching algorithm for comparison of processed mass chromatograms from the two dimensions was developed. The algorithm reports only masses present in bioactive fractions in both dimensions and enable therefore an efficient identification of potential masses that causes the bioactivity. This mass list can be used to search in natural compound database(s) for a rapid evaluation if the mass belongs to an already identified compound or if it is a potentially new one. This strategy enables thorough screening of several hundred crude extracts in one week on one single instrument. PMID- 22086771 TI - A new classification approach for comparing two active treatments when there is no prior projection on which one is better. AB - We developed a new classification approach in this paper to compare two active treatments. This approach is especially useful when there is no prior judgment on which treatment is better and the traditional hypothesis testing approach is thus not applicable. Our method classifies all the possible outcomes into categories and draws conclusions on the difference in the outcome measurement between two treatment arms according to the location of the confidence interval for the treatment difference in the response variable. This method controls the misclassification rate regardless of the true difference in the response between the two treatment arms. The method was applied to a diabetes clinical trial. PMID- 22086772 TI - Evaluation of the effects of plant-derived essential oils on central nervous system function using discrete shuttle-type conditioned avoidance response in mice. AB - Although plant-derived essential oils (EOs) have been used to treat various mental disorders, their central nervous system (CNS) acting effects have not been clarified. The present study compared the effects of 20 kinds of EOs with the effects of already-known CNS acting drugs to examine whether the EOs exhibited CNS stimulant-like effects, CNS depressant-like effects, or neither. All agents were tested using a discrete shuttle-type conditioned avoidance task in mice. Essential oils of peppermint and chamomile exhibited CNS stimulant-like effects; that is, they increased the response rate (number of shuttlings/min) of the avoidance response. Linden also increased the response rate, however, the effect was not dose-dependent. In contrast, EOs of orange, grapefruit, and cypress exhibited CNS depressant-like effects; that is, they decreased the response rate of the avoidance response. Essential oils of eucalyptus and rose decreased the avoidance rate (number of avoidance responses/number of avoidance trials) without affecting the response rate, indicating that they may exhibit some CNS acting effects. Essential oils of 12 other plants, including juniper, patchouli, geranium, jasmine, clary sage, neroli, lavender, lemon, ylang-ylang, niaouli, vetivert and frankincense had no effect on the avoidance response in mice. PMID- 22086773 TI - [Closing the abdominal wall - challenges and possible solutions]. AB - The most common complications after abdominal surgery - wound infections and the development of incisional hernia - are associated with the opening and closing of the abdominal wall. Depending on the selection of patients, wound infection rates of up to 19 % and hernia rates of up to 38 % are reported. Based on a summary of the actual literature, the abdominal wall should be closed with continuous slowly absorbable sutures with a suture length to wound length ratio of over 4 using small stitches. While antiseptic suture material may help to reduce wound infections after abdominal incision, preventing the development of incisional hernia is still a unsolved problem. As there is still no standard surgical technique for abdominal wall closure, surgeons should pay greater attention to the standardisation and documentation of techniques and wound care. PMID- 22086774 TI - [Stem cell-induced liver regeneration]. AB - BACKGROUND: The liver has an excellent regenerative capacity after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSC) to participate in liver regeneration. Here we report our experience with portal vein embolisation (PVE) and CD133+ BMSC administration to the liver, compared with PVE alone, to augment hepatic regeneration in patients with critically low FLRV or impaired liver function. PATIENTS AND METHODS: Eleven patients underwent PVE of liver segments I and IV-VIII to stimulate hepatic regeneration prior to extended right hepatectomy. In these 11 patients with a FLRV below 25% and/or limited quality of hepatic parenchyma, PVE alone did not promise adequate proliferation. These patients underwent additional BMSC administration to segments II and III. Two radiologists blinded to patients' identity and each other's results measured liver and tumour volumes with helical computed tomography. Absolute, relative and daily FLRV gains were compared with a group of patients that underwent PVE alone. RESULTS: The increase of the mean absolute FLRV after PVE with BMSC application from 239.3 mL+/-103.5 (standard deviation) to 417.1 mL+/-150.4 was significantly higher than that from 286.3 mL+/ 77.1 to 395.9 mL+/-94.1 after PVE alone (p<0.05). Also the relative gain of FLRV in this group (77.3%+/-38.2%) was significantly higher than that after PVE alone (39.1%+/-20.4%) (P=0.039). In addition, the daily hepatic growth rate after PVE and BMSC application (9.5+/-4.3 mL/d) was significantly superior to that after PVE alone (4.1+/-1.9 mL/d) (p=0.03). Time to surgery was 27 days+/-11 in this group and 45 days+/-21 after PVE alone (p=0.02). Short- and long-term survival were not negatively influenced by the shorter waiting period. CONCLUSION: In patients with malignant liver lesions, the combination of PVE with CD133+ BMSC administration substantially increased hepatic regeneration compared with PVE alone. This procedure bears the potential to allow the safe resection of patients with a curative intention that would otherwise carry the risk post-operative liver failure. PMID- 22086775 TI - Taming saphenous vein grafts using guide catheter extensions. PMID- 22086776 TI - If i can't get it, i'll make it myself: adversity as the mother of innovation. PMID- 22086777 TI - Transradial PCI in cardiogenic shock, the final frontier? PMID- 22086778 TI - Perforation of the sinus of valsalva by guiding catheter during percutaneous coronary intervention via right transradial approach: a very unusual complication. PMID- 22086779 TI - Integrity(r) coronary stent: a very limber bare-metal stent. PMID- 22086780 TI - Rise of the machines... and their mechanics. PMID- 22086781 TI - The laa occlusion paradigm: are we there yet? PMID- 22086782 TI - Mechanisms of resistance to vascular endothelial growth factor blockade. AB - Angiogenesis is essential for the growth of primary tumors and for their metastasis. This process is induced by factors, such as vascular endothelial growth factors (VEGFs), that bind to transmembrane VEGF receptors (VEGFRs). VEGF A is the primary factor involved with angiogenesis; it binds to both VEGFR-1 and VEGFR-2. The inhibition of angiogenesis by obstructing VEGF-A signaling has been investigated as a method to treat solid tumors, but the development of resistance to this blockade has complicated treatment. The major mechanisms of this resistance to VEGF-A blockade include signaling by redundant receptors, such as the fibroblast growth factors, angiopoietin-1, ephrins, and other forms of VEGF. Other major mechanisms of resistance are increased metastasis of hypoxia resistant tumor cells, recruitment of cell types capable of promoting VEGF independent angiogenesis, and increased circulation of nontumor proangiogenic factors. Additional mechanisms of resistance to VEGF-A blockade include heterogeneity of responsiveness among tumor cells, use of anti-VEGF-A agents at insufficient doses or for insufficient duration, altered sensitivity to anti-VEGF A agents by mutations in endothelial cells or vascular remodeling, maintenance of vascular sleeves that allow for easy regrowth of tumor vasculature upon discontinuation of therapy, vascular cooption, and intussusceptive angiogenesis. An understanding of these mechanisms may lead to the development of targeted therapies that overcome this resistance. Some of these approaches include the combined inhibition of redundant angiogenic pathways, proper patient selection for various therapies based on gene expression profiles, blockade of cellular migration by inhibition of colony-stimulating factor, or the use of agents to disrupt vascular architecture. PMID- 22086783 TI - Dynamic nuclear polarization enhanced solid-state NMR spectroscopy of functionalized metal-organic frameworks. PMID- 22086784 TI - Endoscopic anatomy of the palatovaginal canal (palatosphenoidal canal): a landmark for dissection of the vidian nerve during endonasal transpterygoid approaches. AB - OBJECTIVES/HYPOTHESIS: Demonstrate the endoscopic anatomy of the palatovaginal (PV) canal and artery for identification and dissection of the vidian nerve during endoscopic transpterygoid approaches. Evaluate the length of the PV canal and its relation with the vidian nerve. Show that the traditionally known PV canal is a misnomer and should be renamed. STUDY DESIGN: Experimental study: anatomical and radiological. METHODS: Dissection of eight cadaveric heads was performed to demonstrate the endoscopic anatomy of the PV canal. Computed tomography scan analysis of 20 patients was used to evaluate the length of the PV canal, the angle formed between this canal and the vidian nerve, and the distance between the vidian canal and the PV canal. Study of 10 dry skull bases was performed to verify the structures involved in the formation of the PV canal. RESULTS: Anatomic steps and foundations for dissection of the vidian nerve using the PV canal as a landmark were described. The mean length of the PV canal was 7.15 mm. The mean proximal distance between the vidian and the PV canal was 1.95 mm, and the mean distal distance was 4.14 mm. The mean angle between those canals was 48 degrees. The osteology study showed the vaginal process of the sphenoid bone did not contribute to the formation of the PV canal. CONCLUSIONS: Our anatomic investigations, radiologic studies, and surgical experience demonstrate the important anatomic relationship of the PV canal with the vidian canal and the relevance of the PV canal as a surgical landmark in endoscopic endonasal transpterygoid approaches. Anatomically, PV canal is a misnomer and should be replaced with palatosphenoidal canal. PMID- 22086785 TI - Too little appreciation for great expenditure? Workload and resources in ICUs. AB - PURPOSE: The aim of this study was providing descriptive information and the comparative examination of job strain and mental health of nurses and physicians in different intensive care units (ICU). METHODS: The Effort-Reward Imbalance Questionnaire by Siegrist and standardized psychometric questionnaires, like Hospital Anxiety and Depression Scale, Impact of Event Scale, Brief Symptom Inventory, Social Support Questionnaire, and Life Satisfaction Questionnaire were used. Five ICUs of the same German medical school were included (N = 142). RESULTS: For all ICUs investigated, a significantly lower mental health and a high effort-reward imbalance were found when compared with other samples. Only a few differences between the wards or both professional groups (nurses vs. physicians) were noted. The values for social support were comparable with those of healthy controls but differed between the wards. The life satisfaction in our cohort was lower compared to a population-based sample but was significant different between the wards. CONCLUSIONS: Our study demonstrates the high job strain in an ICU, largely independent of the professional group. Noteworthy, a high effort-reward imbalance was found that stands in positive relation to adverse health effects (anxiety, depression, and general mental health). As a consequence, necessary interventions like stress management, supervision, and communication trainings should consider ward-specific conditions of employment rather than professional affiliation. After these interventions, a follow-up study will be performed to examine beneficial effects on job strain and health. PMID- 22086786 TI - Efficacy of locking plate fixation in stabilizing distal radius fractures in patients aged 50 years or over. PMID- 22086787 TI - Early CT for suspected occult scaphoid fractures. AB - In this study, the use of computed tomography (CT) early in the management of suspected occult scaphoid fractures was evaluated. We retrospectively reviewed the notes and radiology of patients who had scaphoid CT scans over the preceding 3 years. Eighty-four patients that had CT scans within 14 days from injury were identified. Of the CT scans, 64% (n = 54) excluded a fracture and these patients were promptly mobilized. No patients returned with any complications from this management. Overall, 36% of CT scans were abnormal (n = 30), 7% revealed occult scaphoid fractures, 18% revealed occult carpal fractures of the triquetrum, capitate, and lunate, respectively, and 5% revealed distal radius fractures. All patients diagnosed with fractures were successfully managed with plaster immobilization and there was one case of complex regional pain syndrome. Early CT alters therapeutic decision making in suspected occult fractures preventing unnecessary immobilization in a working population without increase in cost. PMID- 22086788 TI - The effect of the involvement of the dominant or non-dominant hand on grip/pinch strengths and the Levine score in patients with carpal tunnel syndrome. AB - The Levine questionnaire is a disease-oriented instrument developed for outcome measurement of carpal tunnel syndrome (CTS) management. The objective of this study was to compare Levine scores in patients with unilateral CTS, involving the dominant or non-dominant hand, before and after carpal tunnel release. Records of 144 patients, 126 women (87%) and 18 men (13%) aged a mean of 58 years with unilateral CTS, treated operatively, were analysed. The dominant hand was involved in 100 patients (69%), the non-dominant in 44 (31%). The parameters were analysed pre-operatively, and at 1 and 6 months post-operatively. A comparison of Levine scores in patients with the involvement of the dominant or non-dominant hand showed no statistically significant differences at baseline and any of the follow-up measurements. Statistically significant differences were noted in total grip strength at baseline and at 6 month assessments and in key-pinch strength at 1 and 6 months. PMID- 22086789 TI - High levels of hsCRP are associated with carbohydrate metabolism disorder. AB - AIM: To determine risk parameters associated with high values of high sensitive C reactive protein (hsCRP) in subjects with different glucose fasting levels. METHODS: Anthropometric parameters, arterial pressure, glycemia, lipid profile, uric acid, and hsCRP were studied in a population of 513 individuals between 40 and 65 years. RESULTS: In total, 349 (68.0%) were normoglycemic (NG); 113 (22.0%) had impaired fasting glucose (IFG); and 51 (9.9%) were diabetic subjects. A multivariate linear regression analysis showed that the natural logarithm of hsCRP was associated significantly with glycemia levels (P = 0.009), uric acid (P = 0.001), diastolic blood pressure (P = 0.011), smoking habit (P = 0.021), BMI (P<0.001), and sex (P<0.001). One-third of the NG subjects had high hsCRP levels. A multiple logistic regression analysis showed that sex and BMI were variables related to high levels of hsCRP in subjects with IFG and NG. In NG subjects, uric acid levels were associated with risk of presenting high hsCRP levels and were higher in women than men. In NG women, ROC curves analysis identified a uric acid level of 3.9 mg/dl as a cut-off point to predict a high value of hsCRP. Those individuals with uric acid values higher than 3.9 mg/dl and normal glycemia had 3.5-fold more risk of having hsCRP levels over 3.0 mg/l. CONCLUSIONS: We sustain that high levels of hsCRP are associated with disturbance in carbohydrate metabolism. In addition, we believe that in low cardiovascular risk population, such as NG women, uric acid levels above 3.9 mg/dl might represent a signal of possible pro-inflammatory state and cardiovascular risk. PMID- 22086790 TI - Latent tuberculosis infection screening for laboratory personnel using interferon gamma release assay and tuberculin skin test in Korea: an intermediate incidence setting. AB - BACKGROUND: Though recent reports have indicated a higher prevalence of latent tuberculosis infection (LTBI) in laboratory personnel than in other healthcare workers, these studies included only a limited number of laboratory personnel. METHODS: We have thus focused on the laboratory personnel, who had a high level of exposure to specimens from patients with TB. We recruited 173 laboratory personnel and performed QuantiFERON-TB Gold In-Tube test (QFT-G) and tuberculin skin test (TST). RESULTS: QFT-G was positive in 21.4% of the enrolled laboratory personnel, and TST was positive in 33.3%. The agreement between the two tests was fair (kappa = 0.234). In multivariate analyses, household contactwith TBpatients (P = 0.013), the laboratory sections of microbiology (P = 0.045) and chemistry/immunology (P = 0.014) were shown to be significantly associated with positive QFT-G results. CONCLUSION: Our data show a high prevalence of TST and QFT-G positivity in laboratory personnel and emphasize the importance of LTBI screening for laboratory personnel. In BCG-vaccinated populations with an intermediate incidence setting, QFT-G seems to be superior to TST as a screening tool for the detection of LTBI. Further study, including results of follow-up tests will be helpful for confirmation of our findings. PMID- 22086791 TI - Troubleshooting fine-tuning procedures for qPCR system design. AB - Quantitative real-time PCR (qPCR) has been improved and optimized over the past decade for a wide range of applications. Design of primers and probes is one of the crucial steps to obtain high system efficiency of qPCR since design pitfalls influence negatively amplification performances. We report the results of some experiments. First, we demonstrate the utility of optimal primer design and concentration in PCR by constructing suboptimal primers, for instance with hairpin and primer-dimers secondarystructures, and quantifying the decrease in efficiency of amplification. Second, we show the adverse effects of the target sequence harboring stable secondary structures on the primer binding sites. Finally, we let see that the mere use of probe-based detection is not enough to ensure robustness of qPCR data, because the eventual detrimental products generated by primers not well designed may influence in any case the PCR efficiency. PMID- 22086792 TI - Naringenin is an inhibitor of human serum paraoxonase (PON1): an in vitro study. AB - BACKGROUND: Inhibition studies on PON1 as an organophosphate-hydrolyzing and atheroprotective enzyme could be useful in elucidating the function of PON1. This study is aimed at examining the in vitro effects of the flavonoid naringenin on PON1 activity in human serum and purified enzyme. METHODS: The inhibition kinetics of the interaction of naringenin with human PON1 in serum and purified enzyme was determined spectrophotometrically using paraoxon and phenylacetate as the substrates. RESULTS: Naringenin could be introduced as an effective inhibitor on purified human PON1 activity for phenylacetate as the substrate with an IC(50) value of 10 uM. Paraoxonase and arylesterase activities of PON1, in the serum assay, were also inhibited by naringenin with IC(50) values of 37.9 and 34.6 uM, respectively. PON1, according to acompetitive-type inhibition pattern, was inhibited by naringenin with K(i) constant of 14.5 uM for serum paraoxonase activity. The results were compared with a known inhibitor of PON1, 2 hydroxyquinoline. We believe (to our knowledge) that this is the first reported study for kinetic parameters of PON1 inhibition by naringenin. CONCLUSIONS: Lipophilic property appears to be an important feature of the structure in evaluating the inhibitor potential. Comparison of our findings and other authors showed that the induction of PON1 gene by naringenin and its inhibitory effects on the enzyme protein are probably two different mechanisms by which the flavonoid affects PON1. The in vitro data reported in this study could be useful in the development of structure-activity relationship for PON1 inhibition. PMID- 22086793 TI - Screening serum biomarkers for early primary hepatocellular carcinoma using a phage display technique. AB - Hepatocellular carcinoma (HCC) occurs mainly in chronically diseased livers following hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Early detection and diagnosis of HCC would be of great clinical benefit. In this study, we used a random phage display peptide library and sera from early-stage primary HCC patients (n = 30) to screen potential serum biomarkers for early primary HCC. Age- and sex-matched patients with HBV and/or HCV infection were used as controls. In the screening phase, 19 out of 20 randomly selected phage clones exhibited specific reaction with purified sera IgG from early primary HCC patients, among them 14 coming from the same phage clone with inserted peptidesequence RGWCRPLPKGEG (named HC1). In the validation phase, phage ELISA results showed that the positive reaction rate of the HC1 phage clone was 91.4% with the early HCC group (n = 70), significantly higher than that with the HBV infection group (20.0%) (n = 70), the HCV infection group (12.9%) (n = 70), the HBV + HCV infection group (24.3%) (n = 70), the cirrhosis group (17.1%) (n = 70), and the healthy control group (10.0%) (n = 70). In conclusion, the HC1 mimic peptide showed high diagnostic validity for early primary HCC, and thereby could be a candidate serum biomarker for early primary HCC. PMID- 22086794 TI - The serum profile of adipokines in naive patients with diabetes mellitus type 2 and obesity. AB - BACKGROUND: The aim of this study was to explore the relationship of serum profile of adipokines with cardiovascular risk factors and anthropometric parameters in patients with diabetes mellitus type 2. SUBJECTS: A population of 108 obese patients with DM2 was analyzed. A complete biochemical anthropometric and nutritional evaluation was performed. RESULTS: In the analysis with leptin as a dependent variable, the IL-6 and glucose levels remained in the model (F = 6.2; P<0.05), with an increase of 5.8 (CI 95%:2.7-7.6) ng/ml with each 1 pg/ml of IL-6 and of 5.2 (CI95%:2.5-5.8) ng/ml with each 1 mg/dl of glucose. In a second model with adiponectin as a dependent variable, the BMI remained in the model (F = 3.77;P<0.05), with an decrease of -3.77 (CI 95%:0.53-7.1) ng/ml with each 1 point of BMI. In the third multivariate analysis with IL-6 as a dependent variable, the glucose level remained in the model (F = 10.1; P<0.01), with an increase of 0.09 (CI95%:0.06-0.12) pg/ml with each 1 mg/dl of glucose. In the fourth multivariate analysis with resistin as a dependent variable, the CRP remained in the model (F = 2.51; P<0.05), with an increase of 0.28 (CI 95%:0.08-0.48) pg/ml with each 1 mg/dl of CRP. CONCLUSION: Serum profile of adipokines is associated with different risk factors in diabetic obese patients. PMID- 22086795 TI - Serum cytokine levels in patients with chronic hepatitis B according to lamivudine therapy. AB - BACKGROUND: Cytokines are known to play critical roles in the pathogenesis of chronic hepatitis B (CHB). However, the relationship between cytokines and treatment responses to drugs for CHB is not clearly defined yet. We measured the serum cytokine levels of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL 8, IL-10, vascular endothelial growth factor, interferon-gamma, tumor necrosis factor- (TNF-alpha), macrophage/monocyte chemotactic protein 1, and epidermal growth factor to elucidate the cytokine expression pattern according to the patients' responses to lamivudine. METHODS: Fifty-eight specimens from 27 CHB patients and 98 specimens from healthy individuals were tested for 12 kinds of cytokines. The patients were grouped as: before treatment, ongoing treatment, duringmaintaining remission, and patients with viral breakthrough owing to resistance against lamivudine. The Evidence Investigator (Randox, Antrim, UK), a protein chip analyzer, was used to quantify serum cytokines. RESULTS: Among 12 cytokines, IL-6, IL-8, IL-10, and TNF-alpha were significantly elevated in patients with resistance against lamivudine compared with patients maintaining response. IL-8, IL-10, and TNF-alpha levels also weak to moderate correlated with ALT and HBV-DNA concentrations. CONCLUSIONS: Serum cytokine levels would reflect the pathological differences of the individual treatment phases and may become useful indices in monitoring the treatment response of CHB. PMID- 22086796 TI - Red cell distribution width (RDW) in the newborn: normative data. AB - AIM: To evaluate the normal range of red blood cell distribution width (RDW) in term and preterm newborns dependent on gestational age. MATERIAL AND METHODS: A total of 1,594 preterm and term neonates were admitted to our neonatology department. Infants were divided into two groups according to their gestational age. Group 1 consisted of infants with <=34 weeks of gestation; group 2 consisted of infants with >=35 weeks of gestation. Infants in Groups I and II were subdivided according to their gestational age. Gestational age, birth weight, sex, hemoglobin and hematocrit, MCV levels of all newborns were recorded, and RDW was compared between the groups. RESULTS: A total of 1,594 newbornswere enrolled in the study. Group 1 (<=34 weeks) consisted of 725 newborns and Group 2 (>=35 weeks) consisted of 869 newborns. The mean normal range of RDW in Group 1 was 17.8 +/- 2.1 and of group II was 16.7 +/- 1.6 (P<0.05). The normal range for RDW values at 32-34 weeks was higher than at 35-36 gestational weeks, and at 37-42 weeks (P = 0.002 and 0.003). CONCLUSION: RDW values at <=34 weeks in newborns are higher than at >=35 weeks. This may be useful in the differential diagnosis of neonatal hematologic diseases together with other red cell parameters. PMID- 22086797 TI - Detection of alpha-globin gene deletions using denaturing high-performance liquid chromatography and multiplex ligation-dependent probe amplification. AB - BACKGROUND: Multiplex ligation-dependent probe amplification (MLPA) has been used to detect deletions and mutations of the alpha-globin gene for diagnosis of alpha thalassemia. MLPA reaction products are usually separated and analyzed by high voltage capillary gel electrophoresis (CGE). The goal of this study was to find and use a cost-effective method to separate and analyze MLPA products. METHODS: Blood samples were collected from China. DNA was extracted and amplified by PCR using fluorescently labeled primers. In this study, denaturing high-performance liquid chromatography (DHPLC) was used to separate and analyze the reaction products. And the optimal separation conditions were determined using nondenaturing columntemperature. RESULTS: The DHPLC conditions were optimized and have been applied to separate MLPA products and 27 of the MLPA products from 50 to 320 bp were well separated. DHPLC was able to separate up to 37 reaction products that differed by 4-12 base pairs and detected target gene deletions by differences in peak size. Compared with CGE, both the specificity and sensitivity of DHPLC for the 107 DNA samples were 100%. CONCLUSIONS: DHPLC could be used to test routinely for alpha-globin gene mutations and deletions. Combined with MLPA, DHPLC is a low-cost, simple to use, accurate technique with practical value. PMID- 22086798 TI - Glutathione S-transferase gene polymorphisms are not major risks for susceptibility to posttransplantation diabetes mellitus in Taiwan renal transplant recipients. AB - Glutathione S-transferase (GST) M1 null genotype has been reported playing a significant role in the diabetes mellitus (DM) susceptibility in Turkish population. We investigated whether the GSTM1, GSTA1, and GSTP1 gene polymorphisms are associated with posttransplantation diabetes mellitus (PTDM) in Taiwan. There were 283 renal transplant recipients (RTRs) enrolled. Polymerase chain reaction-restriction fragment length polymorphism was used for the measurement of GSTA1, M1, and P1 genetic polymorphisms. PTDM was diagnosed according to the American Diabetes Association guidelines. Eight-five patients (30%) were diagnosed with PTDM. The averaged posttransplant follow-up period was 77.9 +/- 27.2 months. Duration from transplantat to diagnosis of PTDM ranged from 0.2 to 103.1 months (19.2 +/- 26.3 months). There were significantly differences between non-DM and PTDM groups in age (50.6 +/- 11.0 vs. 54.6 +/- 9.36 years, P = 0.005), BMI (22.4 +/- 3.6 vs. 24.3 +/- 3.8, P<0.001). The distributions of GSTA1, GSTP1, and GSTM1 genotypes alleles were not significantly different between PTDM and non-DM group. Patients carrying the different GSTA1, GSTP1, and GSTM1 genetic and allelic polymorphisms had no differences for the development of PTDM. These overall results suggested a lack of strong association with GSTA1, GSTP1, and GSTM1 genetic polymorphisms to the susceptibility of PTDM in Taiwanese RTRs. PMID- 22086799 TI - Size and power estimation for the Wilcoxon-Mann-Whitney test for ordered categorical data. AB - We derive an exact variance method for the size and power calculation for the Wilcoxon-Mann-Whitney test for ordered categorical data. The O'Brien-Castelloe approximation implemented in SAS version 9.2 (SAS Institute Inc., Cary, NC, USA) is simplified. Simulation studies show that the exact variance approach tends to be more accurate than the O'Brien-Castelloe approximation and the Zhao-Rahardja Qu method derived under local alternatives. PMID- 22086800 TI - Change, lack of change, and creating optimal change out of chaos. AB - Once again, we consider how to effect practice change at the local and national levels. This issue includes several articles that relate to quality improvement. Some physician actions seem resistant to change, as do the underlying social determinants and processes that lead to what are thought to be avoidable hospitalizations, but we also find that concerted effort, along with standardized orders sets and other avenues, can make a difference. Sometimes, however, our attempts at change can lead to more distraction then efficacy. Here we include articles that place the quality issues in context, report interventions, and advance the types of specific knowledge that allow interventional trials. We also have several articles about cancer screening and follow-up, a subset of quality improvement. PMID- 22086801 TI - Guest family physician commentaries. PMID- 22086802 TI - The patient-center medical home and managed care: times have changed, some components have not. PMID- 22086803 TI - Family physician scope of practice: what it is and why it matters. PMID- 22086804 TI - What services do family physicians provide in a time of primary care transition? PMID- 22086805 TI - Rewarding family medicine while penalizing comprehensiveness? Primary care payment incentives and health reform: the Patient Protection and Affordable Care Act (PPACA). AB - Family physicians' scope of work is exceptionally broad, particularly with increasing rurality. Provisions for Medicare bonus payment specified in the health care reform bill (the Patient Protection and Affordable Care Act) used a narrow definition of primary care that inadvertently offers family physicians disincentives to delivering comprehensive primary care. PMID- 22086806 TI - Variation over time in preventable hospitalization rates across counties. AB - BACKGROUND: The Agency for Health Care Research and Quality developed 14 prevention quality indicators (PQIs), including four PQIs related to preventable hospitalizations for diabetes and one to asthma. Quality indicators vary across counties, but variation over time has not been described. METHODS: The Kentucky Cabinet for Health and Family Services published PQI data for each county in Kentucky in each of the 3 years from 2006 to 2008. Variation and correlations among PQI measures were calculated. RESULTS: PQI rates often varied 10-fold between counties. Repeated measures of four PQIs were highly correlated, suggesting local health care processes that are stable over time. Some PQIs, such as PQI01--emergent complications of blood glucose control--correlated poorly with other measures. Other PQIs are correlated over geography and time, including PQI03 (long-term complications of diabetes); PQI14 (poorly controlled diabetes); and PQI15 (asthma). CONCLUSIONS: These county PQI measures were stable over time. Stability implies that PQI measures were not the result of random processes and did not rapidly shift. However, some health improvement needs varied between counties. Although tailoring health promotion interventions to each county's needs may be complex, stable needs afford time to undertake targeted quality improvement efforts. PMID- 22086807 TI - Do urine cultures for urinary tract infections decrease follow-up visits? AB - BACKGROUND: No major clinical practice guideline recommends ordering a urine culture in the management of uncomplicated urinary tract infections (UTIs). In this era of increasing antibiotic resistance, our objective was to determine if ordering urine cultures for adult women with uncomplicated UTIs provides results that lead to a decrease in follow-up visits for continued UTI symptoms. METHODS: This was a retrospective cohort study from the outpatient family medicine clinic, Madigan Army Medical Center, Tacoma, WA. Seven hundred seventy-nine nondiabetic, nonpregnant, adult (aged 18-65 years) female patients (mean age +/- SD, 32.9 +/- 12.1 years) diagnosed with a UTI from November 2006 through March 2008. The main outcome measure was follow-up outpatient visits within 2 weeks for recurrent UTI symptoms. RESULTS: Of the 779 patients studied, 332 (43%) had no urine culture ordered as part of their management and 447 (57%) had a urine culture ordered. There was no significant difference in the rate of follow-up within 2 weeks for continued UTI symptoms between the cohort without urine culture (28 of 332; 8.4%) and the cohort with urine culture (39 of 447; 8.7%) (chi(2) = 0.021; P = .89). In multivariate logistic regression, ordering a urine culture was not associated with a decreased rate of follow-up visits (adjusted odds ratio, 1.11; 95% CI, 0.65-1.90). CONCLUSIONS: In adult women with uncomplicated UTI, ordering a urine culture was not found to be associated with a decrease in follow-up clinic visits. This finding is consistent with current guidelines that recommend against ordering a urine culture for uncomplicated UTIs. PMID- 22086808 TI - Effect of revised nursery orders on newborn preventive services. AB - OBJECTIVE: Aspects of neonatal care that are the subject of evolving guidelines include hepatitis B virus (HBV) immunization; discharge follow-up recommendations; and prevention of perinatal group B streptococcal (GBS) disease. In 2007, a university hospital's standardized newborn nursery orders were changed to reflect current recommendations in these areas. The objective of the study was to determine the effect of new nursery orders on the quality of care provided to these newborns. METHODS: The study was a retrospective review of medical records, birth certificates, and a computer database of 857 infants. The nursery orders changed in the following ways: (1) physicians had to "opt out" of HBV immunization; (2) discharge follow-up recommendations were based on American Academy of Pediatrics (AAP) recommendations; and (3) AAP recommendations for GBS were followed except blood cultures were not required for certain infants. RESULTS: The percentage of infants receiving HBV immunizations increased from 74% in 2007 to 83% in 2008 (P = .0018). The percentage of infants whose mothers received antibiotics for GBS less than 4 hours before delivery and who received a complete blood count increased from 36% to 83% (P < .0001). The percentage of newborns who had discharge follow-up plans consistent with AAP recommendations did not change significantly. CONCLUSION: A simple change in nursery orders was associated with significant improvement in newborn care. PMID- 22086809 TI - Physician empathy and listening: associations with patient satisfaction and autonomy. AB - PURPOSE: Motivational Interviewing (MI) is used to help patients change their behaviors. We sought to determine if physician use of specific MI techniques increases patient satisfaction with the physician and perceived autonomy. METHODS: We audio-recorded preventive and chronic care encounters between 40 primary care physicians and 320 of their overweight or obese patients. We coded use of MI techniques (eg, empathy, reflective listening). We assessed patient satisfaction and how much the patient felt the physician supported him or her to change. Generalized estimating equation models with logit links were used to examine associations between MI techniques and patient perceived autonomy and satisfaction. RESULTS: Patients whose physicians were rated as more empathic had higher rates of high satisfaction than patients whose physicians were less empathic (29% vs 11%; P = .004). Patients whose physicians made any reflective statements had higher rates of high autonomy support than those whose physicians did not (46% vs 30%; P = .006). CONCLUSIONS: When physicians used reflective statements, patients were more likely to perceive high autonomy support. When physicians were empathic, patients were more likely to report high satisfaction with the physician. These results suggest that physician training in MI techniques could potentially improve patient perceptions and outcomes. PMID- 22086810 TI - Physician counseling for colorectal cancer screening: impact on patient attitudes, beliefs, and behavior. AB - PURPOSE: To determine how often primary care physicians address patient-level health behavioral constructs that are associated with colorectal cancer (CRC) screening and whether physician counseling addressing constructs is associated with favorable changes in patients' attitudes, beliefs, intentions, and subsequent screening. METHODS: We conducted a prospective cohort study of patients eligible for CRC screening and attending routine appointments within two academic primary care clinics (50 patients, 20 primary care clinicians). Patients completed validated measures of behavioral constructs associated with CRC screening (benefits, barriers, susceptibility, self-efficacy, intention, and stage of readiness) before and after their visits. Audio-recorded discussions of CRC screening were coded for conversation addressing constructs. Bivariate and regression analyses estimated associations between discussions that did and did not address constructs and, after the visit, measures of perceived benefits, barriers, susceptibility, self-efficacy, intention, and completion of CRC screening within 6 months. RESULTS: Physicians discussed CRC screening during 38 encounters (76%) and addressed behavioral constructs during 26 (52%). Relative to visits without CRC screening discussion, visits with discussion were associated with increased perceived susceptibility (beta = 0.39; 95% CI, 0.09-0.68) and screening intention (beta = 0.42; 95% CI, 0.11-0.73) after the visit but no significant change in perceived benefits, barriers, or self-efficacy. Within 6 months, 17 of 38 patients (45%) who discussed screening completed screening compared with 0 of 12 patients who did not discuss screening (P = .001). Associations between discussions and outcomes were similar whether or not counseling addressed behavioral constructs. CONCLUSIONS: These findings suggest that physician counseling is associated with increased patient perception of CRC susceptibility, greater screening intention, and completion of screening regardless of whether counseling addresses behavioral constructs. PMID- 22086811 TI - Diabetes and cancer screening rates among Appalachian and non-Appalachian residents of Kentucky. AB - BACKGROUND: Having diabetes may increase the odds of late-stage breast cancer. In Kentucky, the rates of late-stage disease are higher in rural than in urban areas, particularly in rural Appalachia. The objectives of the study were to examine the relationship between diabetes and cancer screening and to determine whether Appalachia residence modifies this association. METHODS: One thousand thirty Kentucky adults responded to a 2008 telephone survey that measured whether they had diabetes; lived in Appalachia; had guideline-concordant screening for breast (mammogram, clinical breast examination), cervical (Papanicolaou), and colorectal (fecal occult blood test or sigmoidoscopy/colonoscopy) cancer; and whether they reported receiving mammograms regularly every 1 to 2 years. RESULTS: Of the subjects, 16% had diabetes, 21% were Appalachian, and 32% were men. In multivariate analysis, women with diabetes had about half the odds of "regular" mammography screening (odds ratio, 0.56) compared with those without diabetes. Men and women in Appalachia had about half the odds of colonoscopy or sigmoidoscopy within the past 10 years (odds ratio, 0.54) compared with those living outside Appalachia. CONCLUSIONS: Both having diabetes and living in Appalachia were negatively associated with current and regular cancer screening. Less screening may explain late-stage diagnosis among these populations. PMID- 22086812 TI - Determinants of mammography in women with intellectual disabilities. AB - BACKGROUND: Women with intellectual disabilities have the same rate of breast cancer as other women but are less likely to undergo screening mammography. Characteristics associated with mammography for women with intellectual disabilities in the United States are unknown. METHODS: This study was based on a secondary data analysis of the Massachusetts Department of Developmental Services database, comparing women who had a mammogram within 2 years with women who had not on variables related to the ecological model. Bivariate analyses, logistic regression, and assessment of interactions were performed. RESULTS: The study sample's (n = 2907) mean age was 54.7 years; 58% lived in 24-hour residential settings, 52% received nursing health coordination, and more than 25% had clinical examination needs (eg, sedation). Residential setting, health coordination, and recent influenza vaccination were all associated with mammography. Having a guardian, higher level of activities of daily living needs, and examination needs (requiring sedation or limited wait time for examinations) were associated with lower rates. Interactions between health coordination and examination needs confirmed the potential of the nurse to ameliorate barriers to mammography. CONCLUSION: Several system-level variables were significantly associated with mammography and, in some cases, seemed to ameliorate intrapersonal/behavioral barriers to mammography. Community agencies caring for intellectually disabled women have potential to impact mammography rates by using health coordination. PMID- 22086813 TI - Do primary care physicians lose contact with their colorectal cancer patients? AB - BACKGROUND: Primary care physicians and patients perceive that they lose contact with each other after a cancer diagnosis. The objective of this study was to determine whether colorectal cancer (CRC) patients are less likely to see their primary care physicians after cancer diagnosis. METHODS: This was a longitudinal cohort study using 1993 to 2001 Surveillance Epidemiology and End Results (SEER) Medicare claims data. Eligible patients were those with stage 0 to 1 and 2 to 3 CRC aged 67 to 89 years at diagnosis. Main measures included the proportion of individuals with a face-to-face primary care visit and mean annual primary care visits per patient at baseline and during 5 years after treatment. RESULTS: Fewer than half of the cancer patients visited with a primary care physician at baseline. In the first year after treatment, patients with stage 0 to 1 CRC (48.9% vs 53.3%; P <= .001) and stage 2 to 3 CRC (43.6% vs 53.4%; P <= .001) significantly increased their likelihood of visiting a primary care physician from baseline. The proportion of patients with stage 0 to 1 CRC with a primary care visit remained relatively stable, and the proportion of patients with stage 2 to 3 CRC decreased somewhat between the first and fifth year after treatment. The findings for mean annual primary care visits per patient roughly paralleled those for the proportion of individuals with a primary care visit. CONCLUSIONS: Elderly patients with CRC, especially stage 2 to 3 CRC, increase rather than decrease contact with primary care providers after diagnosis. More work is needed to understand the care that different physician specialties provide cancer patients and to support their collaboration. PMID- 22086814 TI - Patient satisfaction with breast cancer follow-up care provided by family physicians. AB - PURPOSE: There is little evidence to document patient satisfaction with follow-up care provided by family physicians (FPs)/general practitioners (GPs) to breast cancer patients. We aimed to identify determinants of satisfaction with such care in low-income, medically underserved women with breast cancer. METHODS: This was a cross-sectional study of 145 women who reported receiving follow-up care from an FP/GP. Women were enrolled in California's Breast and Cervical Cancer Treatment Program and were interviewed by phone 3 years after their breast cancer diagnosis. Cleary and McNeil's model, which states that patient satisfaction is a function of patient characteristics, structure of care, and processes of care, was used to understand the determinants of satisfaction. Stepwise logistic regression was used to identify significant predictors. RESULTS: Of the patients interviewed, 73.4% reported that they were extremely satisfied with their treatment by the FP/GP. Women who were able to ask their family physicians questions about their breast cancer had six times greater odds of being extremely satisfied compared with women who were not able to ask any questions. Women who scored the FP higher on the ability to explain things in a way she could understand had higher odds of being extremely satisfied compared with women who scored their family physicians lower. CONCLUSIONS: FPs/GPs providing follow-up care for breast cancer patients should encourage patients to ask questions and must communicate in a way that patients understand. These recommendations are congruent with the characteristics of patient-centered communication for cancer patients enunciated in a recent National Cancer Institute monograph. PMID- 22086815 TI - Opioids for back pain patients: primary care prescribing patterns and use of services. AB - BACKGROUND: Opioid prescribing for noncancer pain has increased dramatically. We examined whether the prevalence of unhealthy lifestyles, psychologic distress, health care utilization, and co-prescribing of sedative-hypnotics increased with increasing duration of prescription opioid use. METHODS: We analyzed electronic data for 6 months before and after an index visit for back pain in a managed care plan. Use of opioids was characterized as "none," "acute" (<=90 days), "episodic," or "long term." Associations with lifestyle factors, psychologic distress, and utilization were adjusted for demographics and comorbidity. RESULTS: There were 26,014 eligible patients. Of these, 61% received a course of opioids, and 19% were long-term users. Psychologic distress, unhealthy lifestyles, and utilization were associated incrementally with duration of opioid prescription, not just with chronic use. Among long-term opioid users, 59% received only short-acting drugs; 39% received both long- and short-acting drugs; and 44% received a sedative-hypnotic. Of those with any opioid use, 36% had an emergency visit. CONCLUSIONS: Prescription of opioids was common among patients with back pain. The prevalence of psychologic distress, unhealthy lifestyles, and health care utilization increased incrementally with duration of use. Coprescribing sedative-hypnotics was common. These data may help in predicting long-term opioid use and improving the safety of opioid prescribing. PMID- 22086816 TI - A meta-analysis of bone mineral density in collegiate female athletes. AB - PURPOSE: In a number of small studies focused on one or two sports, exercise and competitive level has been observed to favor attainment of higher bone mineral density (BMD) in otherwise healthy athletes. We analyzed merged data from 10 studies to determine the effects of competitive level on upper extremity BMD in female athletes across multiple sports. METHODS: This study is a meta-analysis of 10 articles reporting results of similar case-control and cross-sectional studies of BMD in female athletes and nonathletes reporting an effect of athletic participation level. Upper extremity BMD was modeled as an outcome of the level of athleticism using a categorical weighted least squares model and controlling for upper-body impact, age, and body mass index. RESULTS: Upper extremity BMD significantly increased for each level of participation (beta = 0.140; 95% CI, 0.047-0.234), Age and body mass index approached significance but the level of upper extremity impact was not significant in the final model. CONCLUSIONS: Clinicians may see iteratively greater BMD in female patients who compete at increasingly intense athletic levels, with elite athletes having much higher BMD than other patients who are either active or not. Further research is needed to identify direction and causality of the relationship between competitive level and BMD. PMID- 22086817 TI - Sunscreen and melanoma: is our prevention message correct? AB - Many primary care providers advise patients to use sunscreen as a means to reduce their risk for skin cancer, especially cutaneous malignant melanoma (CMM). Despite the availability and promotion of sunscreen for decades, the incidence of CMM continues to increase in the U.S. at a rate of 3% per year. There currently is little evidence that sunscreens are protective against CMM. A number of studies suggest that the use of sunscreen does not significantly decrease the risk CMM, and may actually increase the risk of CMM and sunburns. This paper discusses current information regarding the relationship between sunscreen use and CMM, and how providers may need to alter their advice regarding sunscreen use for CMM prevention. PMID- 22086818 TI - Increasing the supply of women physicians in rural areas: outcomes of a medical school rural program. AB - BACKGROUND: Women physicians are less likely then men to practice in rural areas. With women representing an increasing proportion of physicians, there is concern that this could exacerbate the rural physician shortage. The Physician Shortage Area Program (PSAP) of Jefferson Medical College (JMC) is one of a small number of medical school rural programs shown to be successful in addressing the rural physician shortage; however, little is known about their specific impact on women. METHODS: For 2394 physicians from the 1992 to 2002 JMC graduating classes, the 2007 practice location and specialty for PSAP and non-PSAP graduates were obtained from the Jefferson Longitudinal Study. The relative likelihood of PSAP versus non-PSAP graduates practicing in rural areas was determined for women and men and compared. RESULTS: Women PSAP graduates were more than twice as likely as non-PSAP women to practice in rural areas (31.7% vs 12.3%; relative risk, 2.6; 95% CI, 1.6-4.2). This was similar to the PSAP outcomes for men (51.8% vs 17.7%; relative risk, 2.9, 95% CI, 2.2-3.9; relative risk ratio, 0.9, 95% CI, 0.5-1.5). PSAP outcomes were also similar for women and men practicing rural family medicine and rural primary care. CONCLUSION: These results provide support that medical school rural programs have the potential to help address the serious shortage of women physicians in rural areas, thereby increasing access to care for those living there. PMID- 22086820 TI - "PDSA-ADHD": a newly reported syndrome. AB - We present a satirical case report of a new syndrome, called "plan do study act attention deficit hyperactivity disorder," or PDSA-ADHD. This syndrome is associated with the implementation of multiple simultaneous plan-do-study-act cycles as a quality improvement approach in a health care setting. This case represents a clinical warning sign of quality improvement impairment and suggests a new variant of organizational attention deficit disorder. PMID- 22086819 TI - Information chaos in primary care: implications for physician performance and patient safety. AB - PURPOSE: The purpose of this article is to explore the concept of information chaos as it applies to the issues of patient safety and physician workload in primary care and to propose a research agenda. METHODS: We use a human factors engineering perspective to discuss the concept of information chaos in primary care and explore implications for its impact on physician performance and patient safety. RESULTS: Information chaos is comprised of various combinations of information overload, information underload, information scatter, information conflict, and erroneous information. We provide a framework for understanding information chaos, its impact on physician mental workload and situation awareness, and its consequences, and we discuss possible solutions and suggest a research agenda that may lead to methods to reduce the problem. CONCLUSIONS: Information chaos is experienced routinely by primary care physicians. This is not just inconvenient, annoying, and frustrating; it has implications for physician performance and patient safety. Additional research is needed to define methods to measure and eventually reduce information chaos. PMID- 22086821 TI - Neonatal herpes infection: case report and discussion. AB - Neonatal herpes simplex virus (HSV) infections are often life-threatening. Although sometimes difficult to diagnose, most infections can be treatable when found early. Infection with HSV should be kept high on the differential diagnosis of a febrile newborn younger than 1 month old, and treatment should be strongly considered for infants with certain risk factors, even before definitive culture or polymerase chain reaction results are available. The case presented here exemplifies the benefits of maintaining a high suspicion of and empirically treating for HSV in a 10-day-old febrile infant. PMID- 22086822 TI - Large osteolytic skull tumor presenting as a small subcutaneous scalp lesion. AB - Subcutaneous nodules of the scalp are common and usually benign. We describe a case that presented as a probable inclusion cyst or lipoma of the scalp that was discovered to be a benign osteolytic fibrohistiocytic lesion of the frontoparietal skull. This ultimately was successfully treated by neurosurgery with a craniectomy, tumor excision, and reconstructive cranioplasty. PMID- 22086823 TI - Fitwits MDTM: an office-based tool and games for conversations about obesity with 9- to 12-year-old children. AB - BACKGROUND: Physician feelings of ineffectiveness and family-related barriers hamper childhood obesity discussions. Physicians desire appealing, time-efficient tools to frame and sensitively address obesity, body mass index, physical activity, nutrition, and portion size. Our university design-led coalition codeveloped tools and games for this purpose. METHODS: In this feasibility study, we evaluated physician-level counseling of 9- to 12-year-old children and their parents/caretakers using Fitwits MD (Carnegie Mellon University School of Design, Pittsburgh, PA), a brief, structured intervention with flashcards and take-home games. Residency-based physicians in three low- to mid-level socioeconomic urban offices provided self-report data over 8 months through surveys, comment cards, and interviews. RESULTS: We recruited 33 physicians and 93 preadolescents and families. Child-centered key messages resulted in 7-minute conversations, on average. For those physicians who used Fitwits MD, 96% felt improved comfort and competence and 78% noted barrier reduction. CONCLUSIONS: Fitwits MD improved residency-based physician self-efficacy and emphasized important health education topics regarding office-based childhood obesity discussions with preadolescents and parents/caretakers. PMID- 22086824 TI - Cell-line specific protection by berry polyphenols against hydrogen peroxide challenge and lack of effect on metabolism of amyloid precursor protein. AB - Amyloid precursor protein (APP) altered metabolism, Abeta overproduction/aggregation and oxidative stress are implicated in the development of Alzheimer's disease pathology. Based on our previous data indicating that administration of a polyphenol-rich (PrB) blueberry extract (from wild Vaccinium angustifolium) is memory enhancing in healthy mice and in order to delineate the neuroprotective mechanisms, this study investigated the antioxidant effects of PrB in H2O2-induced oxidative damage, Abeta peptide fibrillogenesis and APP metabolism. PrB suppressed H2O2-initiated oxidation (DCF assay) and cell death (MTT assay) in SH-SY5Y cells. Protective effects were observed on Chinese hamster ovary (CHO) cells overexpressing APP770 carrying the mutation Val717Phe only at high concentrations, while further damage on HEK293 cells was induced after co treatment with 250 uM H2O2 and PrB in comparison with H2O2 alone. Using the thioflavine T assay, blueberry polyphenols inhibited Abeta-aggregation (~70%, 15 ug/mL) in a time-dependent manner, while in the CHO(APP770) cells it had no effect on APP metabolism as assessed by western blot. The results suggest that blueberry polyphenols exhibit antioxidant and/or pro-oxidant properties according to the cellular environment and have no effect on APP metabolism. PMID- 22086825 TI - Serial changes of liver stiffness measured by acoustic radiation force impulse imaging in acute liver failure: a case report. AB - Acoustic radiation force impulse (ARFI) imaging is a new technology used to determine liver elasticity. We report the case of a patient that survived hyperacute-type acute liver failure (ALF) and who showed a dramatic change in the value of shear wave velocity (SWV) measured by ARFI, which corresponded with the severity of her liver damage. The value of SWV increased significantly up to 3.6 +/- 0.3 m/s during the encephalopathy phase and then decreased along with the recovery of liver function, the blood flow of the right portal vein, and the liver volume. These findings suggest the value of SWV in ALF as a reliable marker of liver tissue damage. Further investigations of the pathophysiological significance of SWV in ALF are warranted. PMID- 22086826 TI - Risk assessment models for cancer-associated venous thromboembolism. AB - Venous thromboembolism (VTE) is common in cancer patients, and is associated with significant morbidity and mortality. Several factors, including procoagulant agents secreted by tumor cells, immobilization, surgery, indwelling catheters, and systemic treatment (including chemotherapy), contribute to an increased risk of VTE in cancer patients. There is growing interest in instituting primary prophylaxis in high-risk patients to prevent incident (first-time) VTE events. The identification of patients at sufficiently high risk of VTE to warrant primary thromboprophylaxis is essential, as anticoagulation may be associated with a higher risk of bleeding. Current guidelines recommend the use of pharmacological thromboprophylaxis in postoperative and hospitalized cancer patients, as well as ambulatory cancer patients receiving thalidomide or lenalidomide in combination with high-dose dexamethasone or chemotherapy, in the absence of contraindications to anticoagulation. However, the majority of cancer patients are ambulatory, and currently primary thromboprophylaxis is not recommended for these patients, even those considered at very high risk. In this concise review, the authors discuss risk stratification models that have been specifically developed to identify cancer patients at high risk for VTE, and thus might be useful in future studies designed to determine the potential benefit of primary thromboprophylaxis. PMID- 22086827 TI - Towards quantitative conversion of microalgae oil to diesel-range alkanes with bifunctional catalysts. PMID- 22086828 TI - Renal function and heart failure treatment: when is a loss really a gain? PMID- 22086829 TI - Insanity of left ventricular assist therapy: doing the same thing and expecting different results. PMID- 22086830 TI - Are we there yet? Steps along the way toward implementing evidence-based heart failure guidelines in middle-income countries. PMID- 22086831 TI - Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices. AB - Axial-flow LVADs have become an integral tool in the management of end-stage heart failure. Consequently, nonsurgical bleeding has emerged as a major source of morbidity and mortality in this fragile population. The mechanisms responsible for these adverse events include acquired von Willebrand disease, GI tract angiodysplasia formation, impaired platelet aggregation, and overuse of anticoagulation therapy. Because of ongoing concerns for pump thrombosis and thromboembolic events, the thrombotic/bleeding paradigm has led to a difficult clinical dilemma for those managing patients treated with axial flow LVADs. As the field progresses, advances in the understanding of the pathological mechanisms underlying bleeding/thrombosis risk, careful risk stratification, and potential use of novel anticoagulants will all play a role in the management of the LVAD patient. PMID- 22086832 TI - Severe hemolytic anemia and acute kidney injury after percutaneous continuous flow ventricular assistance. PMID- 22086834 TI - Letter by Siracusano and Girasole regarding article, "Toll-like receptor-mediated inflammatory signaling reprograms cardiac energy Metabolism by repressing peroxisome proliferator-activated receptor gamma coactivator-I signaling". PMID- 22086835 TI - A general framework for estimating volume-outcome associations from longitudinal data. AB - Recently, there has been much interest in using volume-outcome data to establish causal associations between measures of surgical experience or quality and patient outcomes following a surgical procedure, such as coronary artery bypass graft, total hip replacement, and radical prostatectomy. However, there does not appear to be a standard approach to a volume-outcome analysis with respect to specifying a volume measure and selecting an estimation method. We establish the recurrent marked point process as a general framework from which to approach a longitudinal volume-outcome analysis and examine the statistical issues associated with using longitudinal data analysis methods to model aggregate volume-outcome data. We review assumptions to ensure that linear or generalized linear mixed models and generalized estimating equations provide valid estimates of the volume-outcome association. In addition, we provide theoretical and empirical evidence that bias may be introduced when an aggregate volume measure is used to address a scientific question regarding the effect of cumulative experience. We conclude with the recommendation that analysts carefully specify a volume measure that most accurately reflects their scientific question of interest and select an estimation method that is appropriate for their scientific context. PMID- 22086836 TI - Chemopreventive effect of a mixture of Chinese Herbs (antitumor B) on chemically induced oral carcinogenesis. AB - In this study, we evaluated chemopreventive efficacy of Antitumor B, a Chinese herbal mixture of six plants (Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus arvensis L., Dictamnus dasycarpus, and Dioscorea bulbifera) on the development of 4-nitroquinoline-1-oxide (4NQO) induced oral squamous cell carcinomas in A/J mice. Antitumor B, delivered through diet, inhibited 4NQO induced oral cancer development by 59.19%. The reduction of cell proliferation appears to be associated with efficacy of Antitumor B against 4NQO-induced oral cancer in A/J mice. The expression of epidermal growth factor receptor (EGFR) and phosphorylated EGFR (Tyr1173) were down-regulated by Antitumor B. Tissue distribution of Antitumor B was determined using obacunone, matrine, and maackiain as marker chemicals. We found significant amounts of obacunone, matrine, and maackiain in the blood after 1-wk treatment. The concentrations of these three compounds did not increase further at 18 wk, suggesting that plasma concentrations had reached a steady-state level at 1 wk. There was no significant body weight loss and there was no other obvious sign of toxicity in Antitumor B-treated mice. These results suggest that Antitumor B is a promising agent for human oral cancer chemoprevention. PMID- 22086837 TI - pH-responsive aggregation of amphiphilic glyco-homopolymer. AB - The first example of amphiphilic glyco-homopolymers is reported and their aggregation properties as a function of solution pH are studied. Two structurally similar polymers with different hydrophobicity (C8 and C6 alkyl chains) are examined. Both polymers form micelle-type aggregates in aqueous solution. The size and micro-environment of the aggregates are found to be strongly dependent on solution pH because of the state of protonation of the tertiary amine group. At acidic pH, swollen multi-micellar aggregates are formed, presumably because of the electrostatic repulsion among the ammonium ions. At basic pH more compact particles are found, which further co-assemble to generate either garland type (C8) or fractal-aggregates (C6). PMID- 22086839 TI - Pregnancy-associated breast cancer: an entity needing refinement of the definition. PMID- 22086840 TI - Angiotensin converting enzyme insertion/deletion polymorphism and risk of pregnancy hypertensive disorders: a meta-analysis. AB - BACKGROUND: The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been reported inconsistently as being associated with risk of pregnancy hypertensive disorders (PHDs). We examined these associations by performing a meta-analysis. METHODS: Two investigators independently consulted the Medline, Embase, CNKI, and Chinese Biomedicine databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in fixed- and random effects models when appropriate. Subgroup analyses were performed by ethnicity, types of PHD (gestational hypertension, pre-eclampsia and eclampsia), country and Hardy-Weinberg equilibrium (HWE) in controls. RESULTS: This meta-analysis included 30 case-control studies with 3523 cases and 4817 controls. Overall, we found that the DD variant of the ACE I/D polymorphism was associated with a significantly increased PHD risk. In the subgroup analysis by ethnicity, the results suggested that the DD genotype was significantly associated with risk of PHD development among Asians and Caucasians. Moreover, when stratifying by types of PHD, a significantly increased risk was observed for pre-eclampsia. Interestingly, when stratifying by country, a significantly elevated risk was found among 'others' countries (those that were not China or Korea). Limiting the analysis to the studies within HWE, the results were persistent and robust. CONCLUSION: This meta-analysis suggests that the I/D polymorphism of ACE may be associated with PHD risk, especially among Asians and Caucasians. PMID- 22086838 TI - Polarity proteins are required for left-right axis orientation and twin-twin instruction. AB - Two main classes of models address the earliest steps of left-right patterning: those postulating that asymmetry is initiated via cilia-driven fluid flow in a multicellular tissue at gastrulation, and those postulating that asymmetry is amplified from intrinsic chirality of individual cells at very early embryonic stages. A recent study revealed that cultured human cells have consistent left right (LR) biases that are dependent on apical-basal polarity machinery. The ability of single cells to set up asymmetry suggests that cellular chirality could be converted to embryonic laterality by cilia-independent polarity mechanisms in cell fields. To examine the link between cellular polarity and LR patterning in a vertebrate model organism, we probed the roles of apical-basal and planar polarity proteins in the orientation of the LR axis in Xenopus. Molecular loss-of-function targeting these polarity pathways specifically randomizes organ situs independently of contribution to the ciliated organ. Alterations in cell polarity also disrupt tight junction integrity, localization of the LR signaling molecule serotonin, the normally left-sided expression of Xnr 1, and the LR instruction occurring between native and ectopic organizers. We propose that well-conserved polarity complexes are required for LR asymmetry and that cell polarity signals establish the flow of laterality information across the early blastoderm independently of later ciliary functions. genesis 50:219 234, 2012. (c) 2011 Wiley Periodicals, Inc. PMID- 22086841 TI - Speckle reduction imaging of breast ultrasound does not improve the diagnostic performance of morphology-based CAD System. AB - PURPOSE: Speckle reduction imaging (SRI) is a newly developed technique in ultrasound examination. This study aimed to compare the diagnostic performance of SRI and non-SRI breast ultrasound examinations by using a morphology-based computer-aided diagnostic system. METHODS: One hundred ten patients with pathologically proven breast lesions were enrolled consecutively from April 2008 to October 2008. SRI and non-SRI ultrasound images were both obtained at the same examination for each patient. The regions of interest were manually sketched by an experienced physician without histological information. Nineteen practical morphologic features from the extracted contour were calculated and a support vector machine classifier identified the breast tumor as benign or malignant. Conventional binomial receiver operating characteristics curve analysis was used to represent the diagnostic performance of both SRI and non-SRI. RESULTS: Between SRI and non-SRI methods, there were no significant differences in the area under the receiver operating characteristics curve (Az value: 0.82 versus 0.81), the sensitivity (78.9% versus 84.2%), and the specificity (73.6% versus 70.8%). CONCLUSIONS: Based on the morphology study, the performance of breast ultrasound in characterizing the solid breast mass as benign or malignant was not significantly improved with SRI. PMID- 22086842 TI - Palladium-catalyzed decarboxylative C-H bond arylation of thiophenes. PMID- 22086843 TI - Diversity of animal small RNA pathways and their biological utility. AB - Higher eukaryotes employ extensive post-transcriptional gene regulation to accomplish fine control of gene expression. The microRNA (miRNA) family plays important roles in the post-transcriptional gene regulation of broad networks of target mRNA expression. Most miRNAs are generated by a conserved mechanism involving two RNase III enzymes Drosha and Dicer. However, work from the past few years has uncovered diverse noncanonical miRNA pathways, which exploit a variety of other RNA processing enzymes. In addition, the discovery of another abundant small RNA family, endogenous short interfering RNAs (endo-siRNAs), has also broadened the catalogs of short regulatory RNAs. This review highlights recent studies that revealed novel small RNA biogenesis pathways, and discusses their relevance to gene regulatory networks. PMID- 22086844 TI - JmjC-domain containing histone demethylase 1B-mediated p15(Ink4b) suppression promotes the proliferation of leukemic progenitor cells through modulation of cell cycle progression in acute myeloid leukemia. AB - The histone demethylase JHDM1B has been implicated in cell cycle regulation and tumorigenesis. In addition, it has been reported that JHDM1B is highly expressed in various human tumors, including leukemias. However, it is not clearly understood how JHDM1B contributes to acute myeloid leukemia (AML) cell proliferation. In this study, we investigated the cellular and molecular function of JHDM1B in AML cells. In AML cell lines and AML-derived ALDH(hi) (high aldehyde dehydrogenase activity)/CD34(+) cells, the levels of JHDM1B mRNA were significantly higher than in normal ALDH(hi) /CD34(+) cells. Reduction of JHDM1B expression in AML cells inhibited cell proliferation compared to control cells, through induction of G1 cell cycle arrest, an increase in the p15(Ink4b) mRNA and protein expression. JHDM1B mRNA was overexpressed in all 133 AML clinical specimens tested (n = 22, 57, 34, and 20 for M1, 2, 4, and 5 subtypes respectively). Compared to normal ALDH(hi) /CD34(+) cells, JHDM1B gene expression was 1.57- to 1.87-fold higher in AML-derived ALDH(hi) /CD34(+) cells. Moreover, the JHDM1B protein was more strongly expressed in AML-derived ALDH(hi) /CD34(+) cells from compared to normal ALDH(hi) /CD34(+) cells. In addition, depletion of JHDM1B reduced colony formation of AML-derived ALDH(hi) /CD34(+) cells due to induction of p15(Ink4b) expression through direct binding to p15(Ink4b) promoter and loss of demethylation of H3K36me2. In summary, we found that JHDM1B mRNA is predominantly expressed in AML-derived ALDH(hi) /CD34(+) cells, and that aberrant expression of JHDM1B induces AML cell proliferation through modulation of cell cycle progression. Thus, inhibition of JHDM1B expression represents an attractive target for AML therapy. PMID- 22086846 TI - VEGF expression in residual tumor cells in orbital retinoblastoma (IRSS stage III) treated with NACT: a prospective study. AB - We prospectively evaluated vascular endothelial growth factor (VEGF) expression by immunohistochemistry in 22 consecutive IRSS stage III retinoblastoma patients who underwent enucleation after neoadjuvant chemotherapy (NACT). Positive VEGF expression was observed in 6/22 (27.3%) patients. VEGF expression was associated with local progression on MRI prior to enucleation (P = 0.004), pathological scleral (P = 0.023), and extra-scleral tumor extension (P = 0.009). EFS for VEGF positive and negative patients was 0% and 56.25%, respectively (P = 0.0002). OS for VEGF positive patients was 33.33% and 54.69% for VEGF negative patients (P = 0.207). Thus, VEGF in residual tumor cells post-NACT may represent poor response to NACT, potential for local invasion, and inferior outcome. PMID- 22086845 TI - Validation of diagnoses of distress disorders in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A). AB - Research diagnostic interviews need to discriminate between closely related disorders in order to allow comorbidity among mental disorders to be studied reliably. Yet conventional studies of diagnostic validity generally focus on single disorders and do not examine discriminant validity. The current study examines the validity of fully-structured diagnoses of closely-related distress disorders (generalized anxiety disorder, post-traumatic stress disorder, major depressive episode, and dysthymic disorder) in the lay-administered Composite International Diagnostic Interview Version 3.0 (CIDI) with independent clinical diagnoses based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A). The NCS-A is a national survey of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) among 10,148 adolescents. A probability sub-sample of 347 of these adolescents and their parents were administered blinded follow-up K-SADS interviews. Good concordance [area under the receiver operating characteristic curve (AUC)] was found between diagnoses based on the CIDI and the K-SADS for generalized anxiety disorder (AUC = 0.78), post-traumatic stress disorder (AUC = 0.79), and major depressive episode/dysthymic disorder (AUC = 0.86). Further, the CIDI was able to effectively discriminate among different types of distress disorders in the sub sample of respondents with any distress disorder. PMID- 22086847 TI - Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation: long-term results of a prospective trial (National Clinical Trial 00254683). AB - BACKGROUND: Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies. METHODS: Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5-fluorouracil-based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data. RESULTS: In total, 99 patients were included in the study. Twenty-three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false-negative and 10 false positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%. CONCLUSIONS: Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;3501-3511. (c) 2011 American Cancer Society. PMID- 22086848 TI - Expression of NF-kappaB and downstream antioxidant genes in skeletal muscle of hibernating ground squirrels, Spermophilus tridecemlineatus. AB - Many small mammals survive the winter by hibernating, entering long periods of cold torpor that are interspersed with brief periods of arousal back to euthermia. This cycling is accompanied by wide changes in oxygen consumption, perfusion of tissues and ATP turnover, and the arousal period in particular is challenging because of oxidative stress associated with the huge increase in oxygen consumption needed to support thermogenesis by brown adipose tissue and skeletal muscle. Well-developed antioxidant defences are needed. The present study analyses responses of the redox-sensitive transcription factor, NF-kappaB, in skeletal muscle over six points on the torpor-arousal cycle to gain insight into its regulation and role during hibernation. Immunoblotting was used to analyse NF-kappaB p50 and p65 subunit levels, nuclear versus cytoplasmic localization and DNA-binding activity as well as levels and phosphorylation state of the IkappaBalpha inhibitor and the kinase IKK that phosphorylates IkappaBalpha to trigger its dissociation from NF-kappaB. The data were generally consistent with an activation of NF-kappaB during the entrance into torpor with responses including an auto-up-regulation of p50 subunits seen during early torpor and elevated IkappaBalpha protein during arousal. Protein levels of two downstream antioxidant targets showed differential regulation, Mn-superoxide dismutase (MnSOD) rising during early torpor versus heme oxygenase 1 (HO-1) increasing during early arousal. The mRNA transcript levels of p50, p65, HO-1 and MnSOD also showed differential expression over the torpor-arousal cycle. The results suggest that antioxidant defences are up-regulated at specific phases of the torpor arousal cycle and that NF-kappaB mediates such protective responses. PMID- 22086849 TI - ERK1/2 regulation of CD44 modulates oral cancer aggressiveness. AB - Carcinogen-induced oral cavity squamous cell carcinoma (OSCC) incurs significant morbidity and mortality and constitutes a global health challenge. To gain further insight into this disease, we generated cell line models from 7,12 dimethylbenz(a)anthracene-induced murine primary OSCC capable of tumor formation upon transplantation into immunocompetent wild-type mice. Whereas several cell lines grew rapidly and were capable of metastasis, some grew slowly and did not metastasize. Aggressively growing cell lines displayed ERK1/2 activation, which stimulated expression of CD44, a marker associated with epithelial to mesenchymal transition and putative cancer stem cells. MEK (MAP/ERK kinase) inhibition upstream of ERK1/2 decreased CD44 expression and promoter activity and reduced cell migration and invasion. Conversely, MEK1 activation enhanced CD44 expression and promoter activity, whereas CD44 attenuation reduced in vitro migration and in vivo tumor formation. Extending these findings to freshly resected human OSCC, we confirmed a strict relationship between ERK1/2 phosphorylation and CD44 expression. In summary, our findings identify CD44 as a critical target of ERK1/2 in promoting tumor aggressiveness and offer a preclinical proof-of-concept to target this pathway as a strategy to treat head and neck cancer. PMID- 22086850 TI - Regulation of matrix metalloproteinase genes by E2F transcription factors: Rb-Raf 1 interaction as a novel target for metastatic disease. AB - The retinoblastoma (Rb)-E2F transcriptional regulatory pathway plays a major role in cell-cycle regulation, but its role in invasion and metastasis is less well understood. We find that many genes involved in the invasion of cancer cells, such as matrix metalloproteinases (MMP), have potential E2F-binding sites in their promoters. E2F-binding sites were predicted on all 23 human MMP gene promoters, many of which harbored multiple E2F-binding sites. Studies presented here show that MMP genes such as MMP9, MMP14, and MMP15 which are overexpressed in non-small cell lung cancer, have multiple E2F-binding sites and are regulated by the Rb-E2F pathway. Chromatin immunoprecipitation assays showed the association of E2F1 with the MMP9, MMP14, and MMP15 promoters, and transient transfection experiments showed that these promoters are E2F responsive. Correspondingly, depletion of E2F family members by RNA interference techniques reduced the expression of these genes with a corresponding reduction in collagen degradation activity. Furthermore, activating Rb by inhibiting the interaction of Raf-1 with Rb by using the Rb-Raf-1 disruptor RRD-251 was sufficient to inhibit MMP transcription. This led to reduced invasion and migration of cancer cells in vitro and metastatic foci development in a tail vein lung metastasis model in mice. These results suggest that E2F transcription factors may play a role in promoting metastasis through regulation of MMP genes and that targeting the Rb Raf-1 interaction is a promising approach for the treatment of metastatic disease. PMID- 22086852 TI - Nanostructured membranes for enzyme catalysis and green synthesis of nanoparticles. AB - Macroporous membranes functionalized with ionizable macromolecules provide promising applications in high capacity toxic metal capture, nanoparticle syntheses, and catalysis. Our low-pressure membrane approach has good reaction and separation selectivities, which are tunable by varying pH, ionic strength, or pressure. The sustainable green chemistry approach under ambient conditions and the evaluation of a reactive poly(acrylic acid) (PAA)-modified polyvinylidene fluoride (PVDF) membrane is described. Two distinct membrane types were obtained through different methods: 1) a stacked membrane through layer-by-layer assembly for the incorporation of enzymes (catalase and glucose oxidase), providing tunable product yields and 2) Fe/Pd nanoparticles for degradation of pollutants, obtained through an in situ green synthesis. Bioreactor-nanodomain interactions and mixed matrix nanocomposite membranes provide remarkable versatility compared to conventional membranes. PMID- 22086851 TI - GLI1 inhibition promotes epithelial-to-mesenchymal transition in pancreatic cancer cells. AB - The Hedgehog (HH) pathway has been identified as an important deregulated signal transduction pathway in pancreatic ductal adenocarcinoma (PDAC), a cancer type characterized by a highly metastatic phenotype. In PDAC, the canonical HH pathway activity is restricted to the stromal compartment while HH signaling in the tumor cells is reduced as a consequence of constitutive KRAS activation. Here, we report that in the tumor compartment of PDAC the HH pathway effector transcription factor GLI1 regulates epithelial differentiation. RNAi-mediated knockdown of GLI1 abolished characteristics of epithelial differentiation, increased cell motility, and synergized with TGFbeta to induce an epithelial-to mesenchymal transition (EMT). Notably, EMT conversion in PDAC cells occurred in the absence of induction of SNAIL or SLUG, two canonical inducers of EMT in many other settings. Further mechanistic analysis revealed that GLI1 directly regulated the transcription of E-cadherin, a key determinant of epithelial tissue organization. Collectively, our findings identify GLI1 as an important positive regulator of epithelial differentiation, and they offer an explanation for how decreased levels of GLI1 are likely to contribute to the highly metastatic phenotype of PDAC. PMID- 22086853 TI - Plug and play with RNA. AB - Retooling RNA: RNA aptamers are high-affinity ligands that can be assembled with other structures to yield multivalent molecules. These properties have been addressed in two recent studies: One describes a GFP-like RNA reporter used to study the dynamics of endogenous RNA; the other study reports on an aptamer templated assembly of multi-enzyme complexes in bacteria for the controlled production of secondary molecules (see picture). PMID- 22086854 TI - Neuroinvasive flavivirus infections. AB - Flaviviruses, including Dengue, West Nile, Japanese encephalitis, and Tick-borne encephalitis virus, are major emerging human pathogens, affecting millions of individuals worldwide. Many clinically important flaviviruses elicit CNS diseases in infected hosts, including traditional "hemorrhagic" viruses, such as Dengue. This review focuses on the epidemiology, symptomatology, neuropathology, and, specifically, neuropathogenesis of flavivirus-induced human CNS disease. A detailed insight into specific factors priming towards neuroinvasive disease is of clear clinical significance, as well as importance to the development of antiviral therapies and identification of key mechanisms involved in the (re)emergence of specific flaviviruses, including potentially novel or previously unrecognized ones, as neuroinvasive pathogens. PMID- 22086855 TI - Association of aberrations in one-carbon metabolism with molecular phenotype and grade of breast cancer. AB - We have earlier demonstrated the role of aberrant one-carbon metabolism in the etiology of breast cancer. In the current study, we examine the clinical utility of these factors in predicting the subtype of breast cancer and as indicators of disease progression. Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR-amplified fragment length polymorphism (AFLP) approaches were used for genetic analysis. Plasma folate and homocysteine were measured using Axsym folate kit and reverse phase HPLC, respectively. Multiple linear regression models were used to test the predictability of disease progression. Luminal A subtype was associated with late age of onset, higher body mass index and lack of family history of breast cancer. Thymidylate synthase (TYMS) 5'-UTR 28 bp tandem repeat (OR: 2.09, 95% CI: 1.05-4.16) and methylene tetrahydrofolate reductase (MTHFR) C677T (OR: 4.10, 95% CI: 1.40-11.95) were strongly associated with Luminal B. Reduced folate carrier (RFC1) G80A (OR: 2.92, 95% CI: 1.22-6.97) and methionine synthase (MTR) A2756G (OR: 4.71, 95% CI: 1.66 13.31) polymorphisms were associated with LuminA-HH subtype while MTHFR C677T showed association with HER-enriched (OR: 30.41, 95% CI: 6.47-142.91). Cytosolic serine hydroxymethyltransferase (cSHMT) conferred protection against basal-like breast cancer (OR: 0.47, 95% CI: 0.22-0.98). HER-enriched and basal-like subtypes showed positive association with familial breast cancer and inverse association with plasma folate. Hyperhomocysteinemia was observed in Luminal B and basal-like subtypes. Multiple linear regression models of aberrant one-carbon metabolism were found to be moderate predictors of breast cancer grade (area under the receiver operating characteristic curve, C = 0.72, 95% CI: 0.58-0.87, P = 0.008). To conclude, aberrations in one-carbon metabolism predict the subtype of breast cancer and disease progression. PMID- 22086856 TI - Hepatic resection for metastatic gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. AB - BACKGROUND: Before the advent of tyrosine kinase inhibitors (TKIs), surgical resection was the primary treatment for hepatic gastrointestinal stromal tumor (GIST) metastases. Although TKIs have improved survival in the metastatic setting, outcomes after multimodal therapy comprised of hepatectomy and TKIs for GIST are unknown. The objective of this study was to determine whether combination therapy for hepatic GIST metastases is associated with improved overall survival compared with reported outcomes from surgery or TKI therapy alone. METHODS: Demographics, clinicopathologic tumor characteristics, treatments, and outcomes of patients who underwent hepatic resection at 3 high volume centers from 1995 to 2010 were reviewed. RESULTS: In total, 39 patients underwent hepatectomy for metastatic GISTs, and 27 patients received postoperative TKI therapy. At a median follow-up of 39.7 months, 23 patients (59%) experienced recurrence at a median of 18 months. The 1-year, 2-year, and 3 year overall survival rates were 96.7%, 76.8%, and 67.9%, respectively. Median survival was not reached at 5 years. The rates of severe complication and mortality were 10.2% (4 patients) and 2.5% (1 patient), respectively. When controlling for confounders, postoperative TKI therapy was associated with improved survival (hazard ratio, 0.04; 95% confidence interval, 0.01-0.50; P = .006), and extrahepatic disease was associated with worse survival (hazard ratio, 9.51; 95% confidence interval, 1.63-55.7; P = .012). CONCLUSIONS: Overall survival after combination therapy exceeded previous reports for the treatment of metastatic GIST with hepatic resection or TKI therapy alone and was significantly enhanced by postoperative TKI therapy. The results from this study support findings that combination therapy for GIST liver metastases comprised of surgical resection and TKI therapy is more effective than surgery or TKI therapy alone. PMID- 22086857 TI - Paediatric pneumonia or empyema and prior antibiotic use in primary care: a case control study. AB - OBJECTIVES: To investigate the association between hospital presentation for paediatric pneumonia or empyema and prior antibiotic use for respiratory tract infection (RTI). METHODS: Case-control study of children aged 6 months to 16 years presenting to hospital with radiographic evidence of pneumonia or empyema and a history of general practitioner (GP) consultation for the index illness. Cases were recruited from seven hospitals in South Wales between October 2008 and December 2009. Controls were children from the same age group who were diagnosed with an uncomplicated RTI in general practice in the same area and at a similar time of year. Primary data were collected from carers by a self-complete questionnaire, with a subsample compared against general practice records. RESULTS: We recruited 89 eligible cases and 166 eligible controls. Cases were less likely than controls to have been prescribed antibiotics at the first GP consultation for the index illness [odds ratio (OR) 0.53; 95% confidence interval (95% CI) 0.31-0.90]. Stratified analyses revealed that this association was limited to children who consulted a GP <3 days after illness onset (OR 0.23; 95% CI 0.10-0.50). Cases were also less likely to have taken antibiotics before the date of index hospital presentation, but this finding was not statistically significant after adjustment for confounding factors (adjusted OR 0.84; 95% CI 0.47-1.49). CONCLUSIONS: Antibiotics prescribed at the first GP consultation for an RTI may protect against subsequent hospital presentation for pneumonia or empyema in some children. Given the strong rationale against unnecessary antibiotic prescribing, further research is needed to identify which children are most likely to benefit from early antibiotic treatment. PMID- 22086858 TI - Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. AB - The BSAC guidelines on treatment of infectious endocarditis (IE) were last published in 2004. The guidelines presented here have been updated and extended to reflect developments in diagnostics, new trial data and the availability of new antibiotics. The aim of these guidelines, which cover both native valve and prosthetic valve endocarditis, is to standardize the initial investigation and treatment of IE. An extensive review of the literature using a number of different search criteria has been carried out and cited publications used to support any changes we have made to the existing guidelines. Publications referring to in vitro or animal models have only been cited if appropriate clinical data are not available. Randomized, controlled trials suitable for the development of evidenced-based guidelines in this area are still lacking and therefore a consensus approach has again been adopted for most recommendations; however, we have attempted to grade the evidence, where possible. The guidelines have also been extended by the inclusion of sections on clinical diagnosis, echocardiography and surgery. PMID- 22086859 TI - Molecular surveillance of drug-resistant Plasmodium vivax using pvdhfr, pvdhps and pvmdr1 markers in Nouakchott, Mauritania. AB - OBJECTIVES: Plasmodium falciparum and Plasmodium vivax occur in Mauritania. Drug resistant P. falciparum has been reported, but the drug-resistance status of P. vivax is unknown. The aims of the present study were to determine the prevalence of mutant pvdhfr, pvdhps and pvmdr1 genes and of pvmdr1 gene amplification in P. vivax isolates in Nouakchott, the capital city of Mauritania, and to establish a baseline for molecular surveillance of drug-resistant P. vivax in the country. PATIENTS AND METHODS: Between 2007 and 2009, 439 febrile patients were screened for malaria in Nouakchott. The sequences of pvdhfr, pvdhps and pvmdr1 markers in 110 P. vivax isolates were determined by direct sequencing of PCR products. The pvmdr1 gene copy number was determined by real-time PCR. RESULTS: The majority of the isolates with a successful PCR amplification (76/86, 88%) were characterized to be of the wild-type pvdhfr genotype, while the remaining 10 isolates carried the S58R and S117N double mutations. All isolates had the wild-type pvdhps genotype SAKAV. For pvmdr1, 75 of 103 (73%) had the wild-type Y976, and 28 (27%) carried the mutant F976. Most (98%) carried the mutant L1076 codon. Of 105 isolates, 102 (97%) had one copy and 3 (3%) had two copies of the pvmdr1 gene. CONCLUSIONS: The prevalence of mutations associated with antifolate resistance is low in Mauritania. Further studies are required to determine the roles of pvmdr1 mutations and gene amplification in conferring drug resistance. These data will serve as a baseline for further monitoring of drug-resistant malaria. PMID- 22086860 TI - Electrochemical synthesis of indium(0) nanoparticles in haloindate(III) ionic liquids. AB - A synthetic route to indium(0) nanoparticles via an electrochemical reduction of haloindate(III) ionic liquids to indium(I), and its subsequent disproportionation to indium(0) and indium(III) in the bulk electrolyte, is described. In this sustainable method, the ionic liquid acts simultaneously as metal source, templating agent, and stabilising agent, with the electron as the only reducing agent. The nature of the ionic liquid cation is demonstrated to strongly affect the morphology and size distribution of the indium(0) nanoparticles. PMID- 22086861 TI - Inflamm-aging of the stem cell niche: breast cancer as a paradigmatic example: breakdown of the multi-shell cytokine network fuels cancer in aged people. AB - Inflamm-aging is a relatively new terminology used to describe the age-related increase in the systemic pro-inflammatory status of humans. Here, we represent inflamm-aging as a breakdown in the multi-shell cytokine network, in which stem cells and stromal fibroblasts (referred to as the stem cell niche) become pro inflammatory cytokine over-expressing cells due to the accumulation of DNA damage. Inflamm-aging self-propagates owing to the capability of pro-inflammatory cytokines to ignite the DNA-damage response in other cells surrounding DNA damaged cells. Macrophages, the major cellular player in inflamm-aging, amplify the phenomenon, by broadcasting pro-inflammatory signals at both local and systemic levels. On the basis of this, we propose that inflamm-aging is a major contributor to the increase in cancer incidence and progression in aged people. Breast cancer will be presented as a paradigmatic example for this relationship. PMID- 22086862 TI - What every hospitalist should know about the post-bariatric surgery patient. AB - Obesity is a growing worldwide epidemic, increasingly addressed through surgical options for weight loss. Benefits of these operations, such as weight loss and improvement or reversal of obesity-related comorbidities, are well established; however, postoperative complications do occur. This article will evaluate common causes for hospital admissions in the post-bariatric surgery population as they relate to the hospitalist who is often responsible for their care. Here we provide an overview of the most common bariatric procedures currently performed, early postoperative complications, late medical complications (ie, abdominal complaints, weight fluctuations, nutritional deficiencies, and metabolic bone disease), and late surgical complications that often affect these patients and result in hospital admissions. Special attention will be paid to radiologic pearls that can assist in the initial evaluation and diagnosis of these patients. PMID- 22086863 TI - Current or recent pregnancy is associated with adverse pathologic features but not impaired survival in early breast cancer. AB - BACKGROUND: Pregnancy-associated breast cancer (PABC) may be defined as breast cancer diagnosed during pregnancy or within 1 year of giving birth. Conflicting data exist regarding the impact of pregnancy on clinical features and prognosis of breast cancer. METHODS: A single-institution retrospective chart review was performed of 99 patients identified with PABC between 1992 and 2007. Non-PABC controls were matched 2:1 to PABC cases by year of diagnosis and age. The differences in clinical features were compared between cases and controls using chi-square tests. Univariate and multivariate analyses were performed to assess the effect of PABC on survival. RESULTS: Of the 99 PABC cases, breast cancer was diagnosed during pregnancy in 36 patients, and after delivery in 63. PABC cases were more likely than controls to be negative for estrogen receptor (59% vs 31%, P < .0001) and negative for progesterone receptor (72% vs 40%, P < .0001). Cases were also more likely to have advanced T class (P = .0271) and N class (P = .0104) and higher grade tumors (P = .0115). With a median follow-up of 6.3 years for cases and 4.7 years for controls, overall survival did not differ between cases and controls (P = .0787). On multivariate analysis, the independent prognostic factors for overall survival were estrogen receptor status (P = .0031) and N class (P = .0003). The diagnosis of PABC was not an independent prognostic factor (P = .1317). CONCLUSIONS: PABC is associated with more adverse tumor features than non-PABC matched for age and year of diagnosis. After correcting for pathologic features, the diagnosis of PABC is not in itself an adverse prognostic factor for survival. PMID- 22086864 TI - Vitamin D insufficiency in myeloproliferative neoplasms and myelodysplastic syndromes: clinical correlates and prognostic studies. AB - Vitamin D insufficiency is commonly observed in the general population; observational studies have suggested an association with increased risk of cancer development. We examined the clinical and prognostic relevance of low plasma levels of 25-hydroxyvitamin D (25[OH]D) in myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). A total of 409 patients were studied: 247 (60%) with primary myelofibrosis (PMF), 74 (18%) with de novo MDS, 63 (15%) with polycythemia vera (PV), and 25 (6%) with essential thrombocythemia (ET). Plasma 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry; a level lower than 25 ng/mL indicated vitamin D insufficiency and a level lower than 10 ng/mL indicated severe deficiency. The proportion of patients with 25(OH)D insufficiency was significantly greater in PMF (48%) and PV (43%) when compared with ET (28%) and MDS (28%) (P = 0.01). Severe 25(OH)D deficiency was significantly more frequent in ET (12%) and PMF (9%), compared with PV (3%) and MDS (1%) (P = 0.05). There were no significant correlations between 25(OH)D insufficiency, or severe deficiency, and a variety of clinical or laboratory variables in PMF, MDS, or PV. Furthermore, Vitamin D insufficiency did not influence either overall or leukemia-free survival in PMF, MDS, or PV (P > 0.05). We conclude that while hypovitaminosis D is relatively common in MPN and MDS, its clinical relevance for prognosis is limited. PMID- 22086865 TI - Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management. AB - DISEASE OVERVIEW: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell-derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival. DIAGNOSIS: Diagnosis is based on bone marrow morphology. The presence of fibrosis, JAK2/MPL mutation or +9/13q- cytogenetic abnormality is supportive but not essential for diagnosis. Prefibrotic PMF mimics essential thrombocythemia in its presentation and the distinction is prognostically relevant. Differential diagnosis of myelofibrosis should include chronic myelogenous leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. RISK STRATIFICATION: The Dynamic International Prognostic Scoring System-plus (DIPSS-plus) prognostic model for PMF can be applied at any point during the disease course and uses eight independent predictors of inferior survival: age >65 years, hemoglobin <10 g/dL, leukocytes >25 * 10(9) /L, circulating blasts >=1%, constitutional symptoms, red cell transfusion dependency, platelet count <100 * 10(9) /L, and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, -7/7q-, i(17q), inv(3), -5/5q-, 12p- or 11q23 rearrangement). The presence of 0, 1, "2 or 3," and >=4 adverse factors defines low, intermediate-1, intermediate-2, and high risk disease with median survivals of ~15.4, 6.5, 2.9, and 1.3 years, respectively. A >80% two-year mortality is predicted by monosomal karyotype, inv(3)/i(17q) abnormalities, or any two of circulating blasts >9%, leukocytes >=40 * 10(9) /L or other unfavorable karyotype. RISK-ADAPTED THERAPY: Observation alone is adequate for asymptomatic low/intermediate-1 risk disease. Allogeneic stem cell transplantation or experimental drug therapy is considered for intermediate-2/ high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate-1 risk disease. Splenectomy and low-dose radiotherapy are used for drug-refractory splenomegaly. Radiotherapy is also used for the treatment of non-hepatosplenic EMH, PMF-associated pulmonary hypertension, and extremity bone pain. PMID- 22086866 TI - Platinum-catalyzed direct amination of allylic alcohols with aqueous ammonia: selective synthesis of primary allylamines. PMID- 22086867 TI - Fibrous nano-silica (KCC-1)-supported palladium catalyst: Suzuki coupling reactions under sustainable conditions. PMID- 22086868 TI - Similarities and differences between the "relativistic" triad gold, platinum, and mercury in catalysis. AB - Relativistic effects in the valence shell of the elements reach a maximum in the triad Pt-Au-Hg and determine their catalytic activity in organic reactions. In this Review we examine the catalytic activity of Pt, Au, and Hg compounds for some representative reactions, and discuss the respective benefits and disadvantages along with other relevant properties, such as toxicity, price, and availability. For the reactions considered, gold catalysts are generally more active than mercury or platinum catalysts. PMID- 22086869 TI - Quantitative replacement of cetyl trimethylammonium bromide by cationic thiol ligands on the surface of gold nanorods and their extremely large uptake by cancer cells. PMID- 22086870 TI - Intensive short-term chemotherapy regimen induces high remission rate (over 90%) and event-free survival both in children and adult patients with advanced sporadic Burkitt lymphoma/leukemia. AB - The optimal treatment of advanced sporadic Burkitt lymphoma in adults is still a matter of debate. The salutary results of pediatric therapies did open the road for improving the adult outcome. Between May 1988 and March 2009, 71 consecutive patients-46 adults, 25 children-affected by Burkitt lymphoma/leukemia were treated with the same intensive pediatric protocol alternating vincristine, adriamycine and fractionated ciclophosphamide (phase A) with high dose methotrexate and high dose cytarabine (phase B) in four Italian institutions. Eighty-nine per cent of patients were in Stage III-IV or had L3 leukemia. Complete remissions were 67/71 (94.4%), 24/25 (96%) in children, and 43/46 (93.5%) in adults. Toxic deaths were 3/71 (4.2%), all in adults. There were nine relapses (one in children, eight in adults), all but one observed early. After a median observation of 94 months (range 23-275), the Event-Free Survival rate is 92% in children and 71.7% in adults (P = 0.067). The 23 more recent adults received also rituximab, without differences in outcome as compared to patients who did not. Our experience confirms that such an intensive pediatric-derived chemotherapy is feasible and improves the long-term outcome of adults with advanced Burkitt lymphoma. PMID- 22086871 TI - Post-discharge intervention in vulnerable, chronically ill patients. AB - BACKGROUND: Studies suggest that the inpatient to outpatient transition of care is a vulnerable period for patients, and socioeconomically disadvantaged populations may be particularly susceptible. OBJECTIVE: In this prospective cohort study, clustered by hospital, we sought to determine the feasibility and utility of a simple, post-discharge intervention in reducing hospital readmissions. METHODS: Chronically ill Medicaid managed care members were consecutively identified from the discharge records of 10 area hospitals. For patients from the 7 intervention hospitals, trained medical assistants performed a brief telephone needs assessment, within 1 week of discharge, in which issues requiring near-term resolution were identified and addressed. Patients with more complicated care needs were identified according to a 4-domain care needs framework and enrolled in more intensive care management. Patients discharged from the 3 control hospitals received usual care. We used a generalized estimating equation model, which adjusts for clustering by hospital, to evaluate the primary outcome of hospital readmission within 60 days. RESULTS: There were 97 intervention and 130 control patients. Intervention patients were slightly younger and had higher adjusted clinical group (ACG) scores. In unadjusted analysis, the intervention group had lower, but statistically similar, 60-day rehospitalization rates (23.7% vs 29.2%, P = 0.35). This difference became significant after controlling for ACG score, prior inpatient utilization, and age: adjusted odds ratio (OR) [95% confidence interval (CI)] 0.49 [0.24-1.00]. CONCLUSIONS: A simple post-discharge intervention and needs assessment may be associated with reduced recurrent hospitalization rates in a cohort of chronically ill Medicaid managed care patients with diverse care needs. PMID- 22086872 TI - Androgen receptor signals regulate UDP-glucuronosyltransferases in the urinary bladder: a potential mechanism of androgen-induced bladder carcinogenesis. AB - UDP-glucuronosyltransferases (UGTs), major phase II drug metabolism enzymes, play an important role in urinary bladder cancer initiation by detoxifying carcinogens. We aimed to determine if androgens regulate UGT expression via the androgen receptor (AR) pathway in the bladder. Real-time reverse transcription polymerase chain reaction and Western blot analyses were used to assess UGT1A levels in the normal urothelium SVHUC cell line stably expressed with AR and in bladder tissues from AR knockout (ARKO) and castrated male mice. Immunohistochemistry was also performed in radical cystectomy specimens. Dihydrotestosterone (DHT) treatment in SVHUC-AR reduced mRNA expression of all the UGT1A subtypes (19-75% decrease), and hydroxyflutamide antagonized the DHT effects. In contrast, DHT showed only marginal effects on UGT1A expression in SVHUC-Vector. Of note were higher expression levels of UGT1As in SVHUC-Vector than in SVHUC-AR. In ARKO mice, all the Ugt1a subtypes were up-regulated, compared to wild-type littermates. In wild-type male mice, castration increased the expression of Ugt1a8, Ugt1a9, and Ugt1a10. Additionally, wild-type female mice had higher levels of Ugt1a than wild-type males. Immunohistochemical studies showed strong (3+) UGT1A staining in 11/24 (46%) cancer tissues, which was significantly lower than in corresponding benign tissues [17/18 (94%) cases (P = 0.0009)]. These results suggest that androgen-mediated AR signals promote bladder carcinogenesis by down-regulating the expression of UGTs in the bladder. PMID- 22086874 TI - Dysfunctional telomeres promote genomic instability and metastasis in the absence of telomerase activity in oncogene induced mammary cancer. AB - Telomerase is a ribonucleoprotein that maintains the ends of chromosomes (telomeres). In normal cells lacking telomerase activity, telomeres shorten with each cell division because of the inability to completely synthesize the lagging strand. Critically shortened telomeres elicit DNA damage responses and limit cellular division and lifespan, providing an important tumor suppressor function. Most human cancer cells express telomerase which contributes significantly to the tumor phenotype. In human breast cancer, telomerase expression is predictive of clinical outcomes such as lymph node metastasis and survival. In mouse models of mammary cancer, telomerase expression is also upregulated. Telomerase overexpression resulted in spontaneous mammary tumor development in aged female mice. Increased mammary cancer also was observed when telomerase deficient mice were crossed with p53 null mutant animals. However, the effects of telomerase and telomere length on oncogene driven mammary cancer have not been completely characterized. To address these issues we characterized neu proto-oncogene driven mammary tumor formation in G1 Terc-/- (telomerase deficient with long telomeres), G3 Terc-/- (telomerase deficient with short telomeres), and Terc+/+ mice. Telomerase deficiency reduced the number of mammary tumors and increased tumor latency regardless of telomere length. Decreased tumor formation correlated with increased apoptosis in Terc deficient tumors. Short telomeres dramatically increased lung metastasis which correlated with increased genomic instability, and specific alterations in DNA copy number and gene expression. We concluded that short telomeres promote metastasis in the absence of telomerase activity in neu oncogene driven mammary tumors. PMID- 22086875 TI - Protection against myocardial infarction and no-reflow through preservation of vascular integrity by angiopoietin-like 4. AB - BACKGROUND: Increased permeability, predominantly controlled by endothelial junction stability, is an early event in the deterioration of vascular integrity in ischemic disorders. Hemorrhage, edema, and inflammation are the main features of reperfusion injuries, as observed in acute myocardial infarction (AMI). Thus, preservation of vascular integrity is fundamental in ischemic heart disease. Angiopoietins are pivotal modulators of cell-cell junctions and vascular integrity. We hypothesized that hypoxic induction of angiopoietin-like protein 4 (ANGPTL4) might modulate vascular damage, infarct size, and no-reflow during AMI. METHODS AND RESULTS: We showed that vascular permeability, hemorrhage, edema, inflammation, and infarct severity were increased in angptl4-deficient mice. We determined that decrease in vascular endothelial growth factor receptor 2 (VEGFR2) and VE-cadherin expression and increase in Src kinase phosphorylation downstream of VEGFR2 were accentuated after ischemia-reperfusion in the coronary microcirculation of angptl4-deficient mice. Both events led to altered VEGFR2/VE cadherin complexes and to disrupted adherens junctions in the endothelial cells of angptl4-deficient mice that correlated with increased no-reflow. In vivo injection of recombinant human ANGPTL4 protected VEGF-driven dissociation of the VEGFR2/VE-cadherin complex, reduced myocardial infarct size, and the extent of no reflow in mice and rabbits. CONCLUSIONS: These data showed that ANGPTL4 might constitute a relevant target for therapeutic vasculoprotection aimed at counteracting the effects of VEGF, thus being crucial for preventing no-reflow and conferring secondary cardioprotection during AMI. PMID- 22086876 TI - Glycogen synthase kinase-3alpha limits ischemic injury, cardiac rupture, post myocardial infarction remodeling and death. AB - BACKGROUND: The molecular pathways that regulate the extent of ischemic injury and post-myocardial infarction (MI) remodeling are not well understood. We recently demonstrated that glycogen synthase kinase-3alpha (GSK-3alpha) is critical to the heart's response to pressure overload. However, the role, if any, of GSK-3alpha in regulating ischemic injury and its consequences is not known. METHODS AND RESULTS: MI was induced in wild-type (WT) versus GSK-3alpha((-/-)) (KO) littermates by left anterior descending coronary artery ligation. Pre-MI, WT, and KO hearts had comparable chamber dimensions and ventricular function, but as early as 1 week post-MI, KO mice had significantly more left ventricular dilatation and dysfunction than WT mice. KO mice also had increased mortality during the first 10 days post-MI (43% versus 22%; P=0.04), and postmortem examination confirmed cardiac rupture as the cause of most of the deaths. In the mice that survived the first 10 days, left ventricular dilatation and dysfunction remained worse in the KO mice throughout the study (8 weeks). Hypertrophy, fibrosis, and heart failure were all increased in the KO mice. Given the early deaths due to rupture and the significant reduction in left ventricular function evident as early as 1 week post-MI, we examined infarct size following a 48-hour coronary artery ligation and found it to be increased in the KO mice. This was accompanied by increased apoptosis in the border zone of the MI. This increased susceptibility to ischemic injury-induced apoptosis was also seen in cardiomyocytes isolated from the KO mice that were exposed to hypoxia. Finally, Bax translocation to the mitochondria and cytochrome C release into the cytosol were increased in the KO mice. CONCLUSION: GSK-3alpha confers resistance to ischemic injury, at least in part, via limiting apoptosis. Loss of GSK-3alpha promotes ischemic injury, increases risk of cardiac rupture, accentuates post-MI remodeling and left ventricular dysfunction, and increases the progression to heart failure. These findings are in striking contrast to multiple previous reports in which deletion or inhibition of GSK-3beta is protective. PMID- 22086877 TI - Hybrid open endovascular technique for aortic thoracoabdominal pathologies. AB - BACKGROUND: Many authors using a hybrid debranching strategy for the treatment of thoracoabdominal pathologies have reported disappointing results and the initial enthusiasm for the technique has given way to criticism and ambiguity. The aim of the present meta-analysis study was to assess the safety and efficacy of the technique in patients with thoracoabdominal aortic aneurysms or other aortic pathologies. METHODS AND RESULTS: A multiple electronic search was performed on all articles describing hybrid open endovascular repair. Separate meta-analyses were conducted for technical success, visceral graft patency, spinal cord ischemia symptoms, renal insufficiency, and other complications as well as 30 day/in-hospital mortality. Nineteen publications with a total of 507 patients were analyzed. The pooled estimates for primary technical success and visceral graft patency were 96.2% (95% CI, 93.5%-98.2%) and 96.5% (95% CI, 95.2%-97.8%) respectively. A pooled rate of 7.5% (95% CI, 5.0%-11.0%) for overall spinal cord ischemia symptoms was observed; whereas for irreversible paraplegia the pooled rate was 4.5% (95% CI, 2.5%-7.0%). The pooled estimate for renal failure was 8.8% (95% CI, 3.9%-15.5%). The pooled 30-day/in-hospital mortality rate was 12.8% (95% CI, 8.6%-17.0%). During the mean follow-up period of 34.5 (95% CI, 31.5-37.5) months, a total of 119 endoleaks were identified in 111 patients (22.7%). CONCLUSIONS: The repair of thoracoabdominal pathologies by means of hybrid procedures in patients who are poor surgical candidates is still associated with significant morbidity and mortality rates. Future studies may substantiate whether the technique is amenable to amelioration and improvement. PMID- 22086878 TI - Safety and efficacy of allogeneic cell therapy in infarcted rats transplanted with mismatched cardiosphere-derived cells. AB - BACKGROUND: Cardiosphere-derived cells (CDCs) are an attractive cell type for tissue regeneration, and autologous CDCs are being tested clinically. However, autologous therapy necessitates patient-specific tissue harvesting and cell processing, with delays to therapy and possible variations in cell potency. The use of allogeneic CDCs, if safe and effective, would obviate such limitations. We compared syngeneic and allogeneic CDC transplantation in rats from immunologically-mismatched inbred strains. METHODS AND RESULTS: In vitro, CDCs expressed major histocompatibility complex class I but not class II antigens or B7 costimulatory molecules. In mixed-lymphocyte cocultures, allogeneic CDCs elicited negligible lymphocyte proliferation and inflammatory cytokine secretion. In vivo, syngeneic and allogeneic CDCs survived at similar levels in the infarcted rat heart 1 week after delivery, but few syngeneic (and even fewer allogeneic) CDCs remained at 3 weeks. Allogeneic CDCs induced a transient, mild, local immune reaction in the heart, without histologically evident rejection or systemic immunogenicity. Improvements in cardiac structure and function, sustained for 6 months, were comparable with syngeneic and allogeneic CDCs. Allogeneic CDCs stimulated endogenous regenerative mechanisms (cardiomyocyte cycling, recruitment of c-kit(+) cells, angiogenesis) and increased myocardial vascular endothelial growth factor, insulin-like growth factor-1, and hepatocyte growth factor equally with syngeneic CDCs. CONCLUSIONS: Allogeneic CDC transplantation without immunosuppression is safe, promotes cardiac regeneration, and improves heart function in a rat myocardial infarction model, mainly through stimulation of endogenous repair mechanisms. The indirect mechanism of action rationalizes the persistence of benefit despite the evanescence of transplanted cell survival. This work motivates the testing of allogeneic human CDCs as a potential off-the-shelf product for cellular cardiomyoplasty. PMID- 22086879 TI - Treatment of unexplained syncope: a multicenter, randomized trial of cardiac pacing guided by adenosine 5'-triphosphate testing. AB - BACKGROUND: The origin of 40% of syncope cases remains unknown even after a complete diagnostic workup. Previous studies have suggested that ATP testing has value in selecting successful therapy. This patient-blinded, multicenter, randomized superiority trial tested whether, in patients with syncope of unknown origin, selecting cardiac pacing in those with a positive ATP test leads to fewer recurrences than those who do not receive pacing. METHODS AND RESULTS: From 2000 to 2005, 80 consenting patients (mean age, 75.9+/-7.7 years; 81% women; 56% without diagnosed structural heart disease) with syncope of unknown origin and atrioventricular or sinoatrial block lasting >10 seconds (average, 17.9+/-6.8 seconds) under ATP administration (20-mg IV bolus) were recruited from 10 hospitals, implanted with programmable pacemakers, and randomized to either active pacing (dual-chamber pacing at 70 bpm) or backup pacing (atrial pacing at 30 bpm). Patients were followed up regularly for up to 5 years for any syncope recurrence, the primary outcome. Mean follow-up was 16 months. Syncope recurred in 8 of 39 patients (21%) randomized to active pacing and in 27 of 41 (66%) randomized to backup pacing (control), yielding a hazard ratio of 0.25 (95% confidence interval, 0.12-0.56). After recurrence, the 27 recurrent control patients were reprogrammed to active pacing, and only 1 reported subsequent syncope. CONCLUSION: This study suggests that, in elderly patients with syncope of unknown origin and positive ATP tests, active dual-chamber pacing reduces syncope recurrence risk by 75% (95% confidence interval, 44-88). CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com/ISRCTN00029383. Unique identifier: ISRCTN00029383. PMID- 22086880 TI - Comparison of the durations of mild therapeutic hypothermia on outcome after cardiopulmonary resuscitation in the rat. AB - BACKGROUND: Current studies have demonstrated that applying therapeutic hypothermia for 12 to 24 hours after resuscitation from cardiac arrest improves the outcomes of cardiopulmonary resuscitation. The present study investigated whether a shorter duration of therapeutic hypothermia induced quickly and early after resuscitation would provide an equal improvement in the outcomes of cardiopulmonary resuscitation. METHODS AND RESULTS: Ventricular fibrillation was induced and untreated for 8 minutes in 24 male Sprague-Dawley rats. Defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. Seven minutes after resuscitation, animals were randomized into 4 groups (n=6 each): normothermic, hypothermic-2 hours, hypothermic-5 hours, and hypothermic-8 hours. Animals in the hypothermic groups received rapid cooling, which was started 7 minutes after restoration of spontaneous circulation and maintained at 33+/-0.5 degrees C for 2, 5, or 8 hours. Normothermic animals were maintained at 37+/-0.2 degrees C. All animals were anesthetized and ventilated for 8 hours after resuscitation. Blood temperature was significantly decreased in the hypothermic groups. Postresuscitation myocardial function, neurological deficit scores, and 72-hour survival were significantly better in animals treated with hypothermia regardless of the duration of cooling. However, significantly better postresuscitation tissue microcirculation, myocardial ejection fraction, and neurological deficit scores were observed in the hypothermic-2 hours animals. CONCLUSIONS: In a rat model of cardiopulmonary resuscitation, a shorter duration of mild hypothermia induced rapidly and early after restoration of spontaneous circulation improved postresuscitation microcirculation, myocardial and cerebral functions, and survival as well as, or better than, prolonged duration of hypothermia after resuscitation. PMID- 22086881 TI - Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare but important cause of morbidity and mortality in children. METHODS AND RESULTS: We analyzed data from 216 patients <=18 years of age at diagnosis who were enrolled in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Median age at diagnosis and enrollment was 7 and 15 years, respectively. The most frequent presenting symptom was dyspnea (idiopathic/familial PAH, 53%; PAH associated with congenital heart disease, 30%). Presyncope/syncope was more frequent in patients with idiopathic PAH/familial PAH (36%) than in those with PAH associated with congenital heart disease (4%). At diagnosis, mean pulmonary artery pressure and pulmonary vascular resistance index were 56 mm Hg and 17 Wood units . m(2), respectively. Five-year survival from diagnosis for the overall cohort was 74+/-6%, with no significant difference between the idiopathic PAH/familial PAH (n=122, 75+/-7%) and PAH associated with congenital heart disease (n=77, 71+/-13%) cohorts (P=0.53). Older age at diagnosis was the only variable significantly associated with decreased survival from diagnosis. Variables at enrollment that were significantly associated with decreased survival from enrollment included higher pulmonary vascular resistance index, lower-weight z scores, and familial PAH. Additional variables at enrollment, identified in a secondary analysis, that were marginally associated with increased survival from enrollment included acute vasoreactivity (adaptation of conventional pediatric definition; P=0.087) and lower brain natriuretic peptide (P=0.060). None of the 22 patients who were acute responders treated with high dose calcium channel blockade as monotherapy or combination therapy died within 5 years of diagnosis. CONCLUSION: Using REVEAL, we identified key predictors of survival in childhood PAH. Refining these prognostic parameters should help clinicians improve outcomes. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00370214. PMID- 22086882 TI - No association between Parkinson disease alleles and the risk of melanoma. AB - BACKGROUND: Recent data showed that melanoma was more common among patients with Parkinson disease than individuals without Parkinson disease and vice versa. It has been hypothesized that these two diseases may share common genetic and environmental risk factors. METHODS: We evaluated the association between single nucleotide polymorphisms (SNP) selected on the basis of recent genome-wide association studies (GWAS) on Parkinson disease risk and the risk of melanoma using 2,297 melanoma cases and 6,651 controls. RESULTS: The Parkinson disease SNP rs156429 in the chromosome 7p15 region was nominally associated with melanoma risk with P value of 0.04, which was not significant after the Bonferroni correction for multiple comparisons. No association was observed between the remaining 31 Parkinson disease SNPs and the risk of melanoma. The genetic score based on the number of Parkinson disease risk allele was not associated with melanoma risk [OR for the highest genetic score quartile (30-35) vs. the lowest (15-20), 1.13, 95% confidence interval (CI), 0.47-2.70]. CONCLUSION: The Parkinson disease SNPs identified in published GWAS do not seem to play an important role in melanoma development. IMPACT: The Parkinson disease susceptibility loci discovered by GWAS contribute little to the observed epidemiologic association between the Parkinson disease and melanoma. PMID- 22086883 TI - Plasma 25-hydroxyvitamin D and risk of pancreatic cancer. AB - BACKGROUND: Laboratory studies suggest that vitamin D may inhibit pancreatic cancer cell growth. However, epidemiologic studies of vitamin D and pancreatic cancer risk have been conflicting. METHODS: To determine whether prediagnostic levels of plasma 25-hydroxyvitamin D (25[OH]D; IDS Inc.; enzyme immunoassay) were associated with risk of pancreatic cancer, we conducted a pooled analysis of nested case-control studies with 451 cases and 1,167 controls from five cohorts through 2008. Median follow-up among controls was 14.1 years in Health Professionals Follow-Up Study (HPFS), 18.3 years in Nurses' Health Study (NHS), 25.3 years in Physicians' Health Study (PHS), 12.2 years in Women's Health Initiative-Observational Study (WHI), and 14.4 years in Women's Health Study (WHS). Logistic regression was used to compare the odds of pancreatic cancer by plasma level of 25(OH)D. RESULTS: Mean plasma 25(OH)D was lower in cases versus controls (61.3 vs. 64.5 nmol/L, P = 0.005). In logistic regression models, plasma 25(OH)D was inversely associated with odds of pancreatic cancer. Participants in quintiles two through five had multivariable-adjusted ORs (95% confidence intervals) of 0.79 (0.56-1.10), 0.75 (0.53-1.06), 0.68 (0.48-0.97), and 0.67 (0.46-0.97; P(trend) = 0.03), respectively, compared with the bottom quintile. Compared with those with insufficient levels [25[OH]D, <50 nmol/L], ORs were 0.75 (0.58-0.98) for subjects with relative insufficiency [25[OH]D, 50 to <75 nmol/L] and 0.71 (0.52-0.97) for those with sufficient levels [25[OH]D, >= 75 nmol/L]. No increased risk was noted in subjects with 25(OH)D >=100 nmol/L, as suggested in a prior study. In subgroup analyses, ORs for the top versus bottom quartile of 25(OH)D were 0.72 (0.48-1.08) for women, 0.73 (0.40-1.31) for men, and 0.73 (0.51 1.03) for Whites. CONCLUSIONS: Among participants in five large prospective cohorts, higher plasma levels of 25(OH)D were associated with a lower risk for pancreatic cancer. IMPACT: Low circulating 25(OH)D may predispose individuals to the development of pancreatic cancer. PMID- 22086885 TI - Statistics for school nursing practice. PMID- 22086884 TI - Lead, calcium uptake, and related genetic variants in association with renal cell carcinoma risk in a cohort of male Finnish smokers. AB - BACKGROUND: Lead is classified as a probable human carcinogen. However, its role in renal cell cancer (RCC) has not been established. Calcium and vitamin D may off-set toxicity in vivo. METHODS: In this nested case-control study, whole blood lead, total serum calcium, and serum 25-hydroxyvitamin D levels were measured in blood drawn prior to diagnosis among male smokers participating in the Alpha Tocopherol, Beta-Carotene Cancer Prevention Study. Single-nucleotide polymorphisms (SNP) in five genes (CALB1, TRPV5, TRPV6, VDR, and ALAD) related to lead toxicity or calcium transport were genotyped. Logistic and linear regressions were used to determine RCC risk and time to diagnosis (respectively), adjusting for other risk factors. RESULTS: Among 154 newly diagnosed cases and 308 matched controls, RCC was associated with higher whole blood lead [OR = 2.0; 95% confidence interval (CI), 1.0-3.9; quartile 4 (Q4) vs. Q1, P(trend) = 0.022] and CALB1 rs1800645 (P(trend) = 0.025, minor 'T' allele frequency = 0.34). Higher total serum calcium (P(trend) <= 0.001) was associated with reduced RCC risk. Total serum calcium and 25-hydroxyvitamin D levels did not alter the association observed with lead. Time from enrollment to RCC diagnosis was positively associated with serum calcium (P(trend) = 0.002) and 25-hydroxyvitamin D (P(trend) = 0.054) among cases. CONCLUSIONS: Higher blood lead concentrations, below the 10 MUg/dL level of concern, were associated with RCC, independent from serum calcium and CALB1 promoter polymorphism. IMPACT: Increased risk of RCC is associated with lower serum calcium and higher whole blood lead in smokers. The clinical prognostic value of serum calcium and vitamin D in RCC should be further investigated. PMID- 22086887 TI - Vaccines for measles, mumps, rubella, varicella, and herpes zoster: immunization guidelines for adults. AB - Although vaccinations are most commonly associated with the pediatric population, it is important for healthcare professionals to be familiar with the vaccines that are recommended for adults. The authors discuss 3 vaccines-the measles, mumps, and rubella (MMR) vaccine, the varicella vaccine, and the herpes zoster vaccine-including information about the diseases and complications that they protect against. Two doses, separated by 4 weeks, of both the MMR and varicella vaccines are recommended for all adults who do not have immunization or contraindications. All adults aged 60 years or older should receive a single dose of the herpes zoster vaccine unless they have contraindications. These 3 vaccines offer protection from illnesses that can have serious sequelae and substantial public health implications. PMID- 22086888 TI - A shot at hepatitis prevention. AB - Recent trends suggest that the prevalence of hepatitis infection has declined in populations vaccinated against the hepatitis viruses. Still, with an estimated 20,000 new infections annually in the United States from human hepatitis A virus, as many as 100,000 annual cases of acute infection from hepatitis B virus, and more than 1 million individuals with chronic hepatitis B virus infection, there is room for further improvement. Although hepatitis A virus infection causes debilitating symptoms and illness, it is typically not a protracted illness, and it usually resolves over weeks to months without further sequelae. By contrast, hepatitis B may convert to a chronic infection that leads to cirrhosis and hepatocellular carcinoma, underscoring the importance of vaccinations in at-risk individuals. PMID- 22086889 TI - Protecting the world against meningitis: new recommendations from the CDC's advisory committee on immunization practices. AB - Meningococcal meningitis is a rare but often fatal disease. Throughout adolescence, the incidence of meningococcal meningitis increases, reaching a peak among individuals between the ages of 16 and 21 years. Vaccines are available to combat this deadly disease. Recently, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices updated its recommendations on meningitis vaccination to improve outcomes and to prevent this disease in adolescents and other vulnerable populations, such as adults traveling internationally to epidemic areas. Improved meningitis vaccines and revised vaccination recommendations will help to create a healthier world. PMID- 22086890 TI - Time for changes in pneumococcal vaccination of adults? AB - Because Streptococcus pneumoniae continues to be an important cause of morbidity and mortality, especially among young children and elderly adults, Healthy People 2020 includes several objectives for decreasing invasive pneumococcal disease and increasing pneumococcal vaccine uptake. Current recommendations of the Advisory Committee on Immunization Practices regarding pneumococcal vaccination for adults have not changed appreciatively in several years. However, it is possible that ongoing research may lead to changes in these recommendations within the next few years. Since the licensure of the 7-valent pneumococcal conjugate vaccine for children in 2000, impressive decreases in pneumonia-related diseases caused by strains in the vaccine have been noted among all age groups receiving vaccination. Coupled with continued concerns about the efficacy of the 23-valent pneumococcal polysaccharide vaccine for adults, particularly in regard to nonbacteremic pneumonia, questions are raised about the potential efficacy and viability of conjugate vaccines for adults. PMID- 22086891 TI - Revisiting the influenza vaccine. AB - The Centers for Disease Control and Prevention (CDC) has declared the decline in preventable diseases through vaccination to be 1 of the 10 great public health achievements in the past decade in the United States. Still, influenza epidemics occur every year in the United States and are associated with high rates of morbidity and mortality. A substantial portion of the US population chooses not to get vaccinated against influenza despite the illness and death associated with the disease. Low rates of vaccination are of particular concern in high-risk patients. The CDC's Advisory Committee on Immunization Practices has broadened its influenza vaccine recommendations to include all individuals older than 6 months. Education of patients about the value of influenza vaccination will help to increase vaccination rates. PMID- 22086892 TI - Vaccinations recommended during pregnancy and breastfeeding. AB - Optimal protection against preventable diseases for the pregnant woman and her fetus can be provided through vaccination prior to pregnancy. When indicated, however, the benefits of immunization during pregnancy and breastfeeding may outweigh the theoretical risks of potential adverse events. Several vaccinations recommended by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention (CDC) can reduce maternal and fetal morbidity and mortality from preventable diseases. Physicians can maintain the highest standards of clinical practice by advocating for appropriate vaccinations in their female patients. The authors discuss current versions of CDC vaccination recommendations, contraindications, and precautions for pregnant and breastfeeding women. PMID- 22086893 TI - Update on the advisory committee on immunization practices' recommendations for use of herpes zoster vaccine. AB - A live attenuated vaccine to prevent herpes zoster, or shingles (Zostavax; Merck & Co Inc, Whitehouse Station, NJ), is approved by the US Food and Drug Administration (FDA) for use in adults aged 50 years or older. Studies show that this vaccine is safe when administered to immunocompetent adults. Investigations are being conducted to evaluate the long-term safety and efficacy of the vaccine in immunocompromised populations, including patients who are dependent on steroids. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention recommends that this vaccine be routinely administered only to patients aged 60 years or older. As more data regarding duration of immunity after vaccination become available and as concerns regarding supply of this vaccine are adequately addressed, the ACIP plans to reconsider its recommendations regarding its use in patients aged 50 to 59 years. The author provides an overview of the herpes zoster vaccine, focusing on the latest extension in use approved by the FDA and the recommendations of the ACIP. PMID- 22086894 TI - Cracking the shell on egg-hypersensitive patients and egg-containing vaccines. AB - Hens' eggs are a common food in the American diet. They are consumed as a primary food source and added as an ingredient to other foods. In individuals who are hypersensitive to eggs, egg-containing foods can cause mild to severe allergic reactions if ingested. These individuals may also have adverse reactions to vaccines produced on egg media. Vaccines that are created on egg media include those for measles, mumps, and rubella; rabies; yellow fever; and influenza. The authors discuss recent developments in the use of egg-containing vaccines in hypersensitive patients. PMID- 22086895 TI - Tdap vaccine: current indications for adolescent and adult patients in the United States. AB - Despite the availability of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in the United States since 2005, the vaccine remains underutilized and perhaps misunderstood by many physicians. Pertussis continues to be a major public health problem, with adults being the primary source of infectious transmission to unprotected infants. Consequently, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices has expanded the indications for the Tdap vaccine. In addition, the vaccine can be safely administered regardless of the time since the patient's last tetanus-diphtheria booster. Widespread use of the Tdap vaccine-especially in health-care workers, adolescents, and adults aged 19 to 64 years-should greatly reduce the incidence of Bordetella pertussis infection in the United States. The recent Food and Drug Administration approval of the Tdap vaccine for individuals aged 65 years or older should increase the use of this vaccine. PMID- 22086896 TI - The cancer biomarker osteopontin: combination with other markers. AB - Osteopontin (OPN) is a biomarker for cancer progression and prognosis in multiple tumor types, however, it has not yet found entry into clinical diagnostics. In recent years, there has been an increasing recognition that marker combinations may have better diagnostic or prognostic potential than individual molecules. While various studies have analyzed OPN in conjunction with other markers, a comprehensive review of their published results is still lacking. OPN in tumor tissue or in the blood has been investigated in conjunction with a broad range of other markers in diverse types of cancer. OPN has been combined with cancer specific markers, functionally converging biomolecules (angiogenesis, motility/adhesion, extracellular matrix, bone) and synergizing biomolecules (fibrinolytic system, calcium homeostatic proteins, squamous cell carcinoma antigen, NF-kappaB pathways, proteases). Clinical parameters of interest have been cancer detection, assessment of progression, and prognosis/treatment response. Some marker combinations with OPN are promising for detection, diagnosis or prognosis in various types of cancer. Yet, surprisingly, in many cases, the published results are conflicting, and no clear metrics have been developed for utilizing marker combinations in clinical decision making. With the current intense interest in multiplex marker panels, additional, large-scale studies are needed to realize the full diagnostic and prognostic potential of OPN. PMID- 22086897 TI - Early detection of ovarian cancer in samples pre-diagnosis using CA125 and MALDI MS peaks. AB - AIM: A nested case-control discovery study was undertaken to test whether information within the serum peptidome can improve on the utility of CA125 for early ovarian cancer detection. MATERIALS AND METHODS: High-throughput matrix assisted laser desorption ionisation mass spectrometry (MALDI-MS) was used to profile 295 serum samples from women pre-dating their ovarian cancer diagnosis and from 585 matched control samples. Classification rules incorporating CA125 and MS peak intensities were tested for discriminating ability. RESULTS: Two peaks were found which in combination with CA125 discriminated cases from controls up to 15 and 11 months before diagnosis, respectively, and earlier than using CA125 alone. One peak was identified as connective tissue-activating peptide III (CTAPIII), whilst the other was putatively identified as platelet factor 4 (PF4). ELISA data supported the down-regulation of PF4 in early cancer cases. CONCLUSION: Serum peptide information with CA125 improves lead time for early detection of ovarian cancer. The candidate markers are platelet-derived chemokines, suggesting a link between platelet function and tumour development. PMID- 22086898 TI - The role of metalloendopeptidases in oropharyngeal carcinomas assessed by tissue microarray. AB - The goal of this study was to investigate the expression of some metalloendopeptidases in squamous cell carcinomas of the oropharynx as well as its relation to histological differentiation, staging of disease, and prognosis. Paraffin blocks from 21 primary tumors were obtained from archives of the Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP/EPM. Immunohistochemistry was used to detect the expression of EP24.15 and EP24.16 by means of tissue microarrays. Expression of EP24.15 or EP24.16 was not correlated with the stage of disease, histopathological grading or recurrence in squamous cell carcinomas of the oropharynx. In summary, our results support the notion that EP24.15 and EP24.16 are expressed in carcinoma of the oropharynx; however, these do not appear to be suitable biomarkers for histological grading, disease stage or recurrence as depicted by tissue microarrays and immunohistochemistry. PMID- 22086900 TI - Favourable response to plasma exchange in tumefactive CNS demyelination with delayed B-cell response. AB - We report a case of multiple sclerosis-associated fulminant tumefactive demyelinating lesion (TDL) with the special feature of delayed humoral immune response. Plasma exchange (PE) yielded significant benefit in two consecutive steroid-unresponsive relapses, while signs of an intrathecal B-cell response were only present 2 years later at the second relapse. Remission was achieved and sustained thereafter with natalizumab. Our case indicates that PE might be a therapeutic option even when the B-cell response is not fully developed. This delay in the development of a humoral immune response may reflect the step-wise B cell colonization of the CNS and represent an attractive therapeutic window of opportunity. PMID- 22086901 TI - Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy. AB - BACKGROUND: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy. METHODS: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population. RESULTS: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the 'central memory like' Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy. CONCLUSIONS: The selective increase of 'central memory-like' subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy. PMID- 22086902 TI - Effect of condensed tannins addition on the astringency of red wines. AB - Astringency has been defined as a group of sensations involving dryness, tightening, and shrinking of the oral surface. It has been accepted that astringency is due to the tannin-induced interaction and/or precipitation of the salivary proline-rich proteins (PRPs) in the oral cavity, as a result of the ingestion of food products rich in tannins, for example, red wine. The sensory evaluation of astringency is difficult, and the existence of fast and reliable methods to its study in vitro is scarce. So, in this work, the astringency of red wine supplemented with oligomeric procyanidins (condensed tannins), and the salivary proteins (SP) involved in its development were evaluated by high performance liquid chromatography analysis of human saliva after its interaction with red wine and by sensorial evaluation. The results show that for low concentration of tannins, the decrease of acidic PRPs and statherin is correlated with astringency intensity, with these families having a high relative complexation and precipitation toward condensed tannins comparatively to the other SP. However, for higher concentrations of tannins, the relative astringency between wines seems to correlate's to the glycosylated PRPs changes. This work shows for the first time that the several families of SP could be involved in different stages of the astringency development. PMID- 22086903 TI - Effects of robot-assisted gait training on cardiopulmonary fitness in subacute stroke patients: a randomized controlled study. AB - BACKGROUND: . Robot-assisted gait training has the potential to improve cardiopulmonary fitness after stroke, even for patients who are in the early stages of recovery and not independent ambulators. The authors compared the effects of robot-assisted gait training and conventional physical therapy on cardiopulmonary fitness. METHODS: . A prospective single-blinded, randomized controlled study of 37 patients receiving inpatient rehabilitation was performed within 1 month after stroke onset. The robot-assisted gait training group (n = 20) received 40 minutes of gait training with Lokomat and 60 minutes of conventional physical therapy each day, whereas the control group (n = 17) received 100 minutes of conventional physical therapy daily. Using a semirecumbent cycle ergometer, changes in cardiopulmonary fitness were investigated using incremental exercise testing. Motor and gait functional recovery was measured according to changes in the lower-extremity score of the Fugl-Meyer Assessment Scale (FMA-L), leg score of the Motricity Index (MI-L), and the Functional Ambulation Category (FAC). RESULTS: . Compared with the control group, the robot group showed 12.8% improvement in peak VO(2) after training (P < .05). Compared with the control group, the robot group also improved in FMA-L score (P < .05). CONCLUSION: . Patients can be trained to increase their VO(2) and lower-extremity strength using a robotic device for stepping during inpatient rehabilitation. This training has the potential to improve cardiopulmonary fitness in patients who are not yet independent ambulators, but that may require more than 2 weeks of continued, progressive training. PMID- 22086904 TI - Widespread interspecific divergence in cis-regulation of transposable elements in the Arabidopsis genus. AB - Transposable elements (TEs) are so abundant and variable that they count among the most important mutational sources in genomes. Nonetheless, little is known about the genetics of their variation in activity or silencing across closely related species. Here, we demonstrate that regulation of TE genes can differ dramatically between the two closely related Arabidopsis species A. thaliana and A. lyrata. In leaf and floral tissues of F1 interspecific hybrids, about 47% of TEs show allele-specific expression, with the A. lyrata copy being generally expressed at higher level. We confirm that TEs are generally expressed in A. lyrata but not in A. thaliana. Allele-specific differences in TE expression are associated with divergence in epigenetic modifications like DNA and histone methylation between species as well as with sequence divergence. Our data demonstrate that A. thaliana silences TEs much better than A. lyrata. For long terminal repeat retrotransposons, these differences are more pronounced for younger insertions. Interspecific differences in TE silencing may have a great impact on genome size changes. PMID- 22086905 TI - Role for ion transport in porcine vocal fold epithelial defense to acid challenge. AB - OBJECTIVE: The vocal fold epithelium is routinely exposed to gastric contents, including acid and pepsin, during laryngopharyngeal reflux events. The epithelium may possess intrinsic defenses to reflux. The first objective of the current study was to examine whether vocal fold epithelial ion transport is one potential mechanism of defense to gastric contents. The second objective was to determine whether ion transport in response to gastric contents is associated with the secretion of bicarbonate. STUDY DESIGN: Prospective design in excised porcine larynges. SETTING: Laboratory. SUBJECTS AND METHODS: Porcine vocal folds (N = 56) were exposed on the luminal surface to acid, pepsin, or sham challenges. Ion transport at baseline and following challenge exposure was measured using electrophysiological techniques. To examine specific ion transport mechanisms, vocal folds were pretreated with either a sodium channel blocker or bicarbonate channel blocker. RESULTS: Within 60 seconds of acid but not pepsin exposure, there was a significant increase in ion transport. This rapid increase in ion transport was transient and related to bicarbonate secretion. CONCLUSION: The current data suggest that porcine vocal folds immediately increase bicarbonate secretion following exposure to acid. Bicarbonate secretion may act to neutralize acid. These findings contribute to the identification of the mechanisms underlying vocal fold defense to reflux and offer implications for the development of treatments for reflux-induced vocal fold injury. PMID- 22086906 TI - Suppression of G-protein-coupled receptor kinase 3 expression is a feature of classical GBM that is required for maximal growth. AB - G-protein-coupled receptor kinases (GRK) regulate the function of G-protein coupled receptors (GPCR). Previously, we found that GPCR (CXCR4)-mediated astrocytoma growth was dependent upon abnormally sustained CXCR4 signaling and was correlated with decreased GRK-mediated receptor phosphorylation. As CXCR4 has also been implicated in the stimulation of high-grade glioma growth, we sought to determine whether dysregulation of GRK expression and/or function might also be present in high-grade gliomas. In an analysis of data from The Cancer Genome Atlas, we found that GRK3 expression is frequently decreased in glioblastoma (GBM) of the classical subtype, which possesses signature amplification or mutational activation of the epidermal growth factor (EGF) receptor. We tested the correlation between GRK3 expression and GBM subtypes, as well as the relationship between the activation of the EGF and other growth factor receptor pathways and GRK expression. In analyses of primary GBM tissue and RNA specimens, we found that GRK3 expression is correlated with established criteria for GBM subtyping including expression of EGF receptor, platelet-derived growth factor receptor (PDGFR)alpha, NF1, PTEN, CDKN2A, and neurofilament. We also found that established drivers of gliomagenesis, the EGF, PDGF, and TGF-beta pathways, all regulate GRK expression. Coculture experiments, designed to mimic critical interactions between tumor and brain microvascular endothelial cells, showed that specifically increasing GRK3 expression reduced the trophic effect of endothelial cells on tumor cells. Together, these experiments show that GRK3 is a negative regulator of cell growth whose expression is preferentially reduced in GBM of the classical subtype as a consequence of activity in primary gliomagenic pathways. PMID- 22086909 TI - DNA replication occurs in all lamina positive micronuclei, but never in lamina negative micronuclei. AB - A micronucleus is a small nucleus-like structure found in the cytoplasm of dividing cells that suffered from genotoxic stress. It is generally hypothesised that micronuclei content is eventually lost from cells, though the mechanism of how this occurs is unknown. If DNA located within the micronucleus is not replicated, it may explain the loss of micronuclei content. Because there had been no compelling evidence for this issue, we have addressed whether DNA located within the micronucleus is replicated this issue. Pulse labelling of bromodeoxyuridine revealed that DNA synthesis takes place in a portion of micronuclei that contain nuclear lamin B protein. By using iodine 3' deoxyuridine/chlorodeoxyuridine double labelling, we found that all micronuclei containing lamin B are replicated during one cell cycle, whereas micronuclei lacking lamin B are never replicated. This result suggests that the content of lamin B-negative micronuclei is lost during cell division. Furthermore, we simultaneously visualised sites of DNA synthesis, lamin B and the extrachromosomal double minutes chromatin, which contain amplified oncogenes. We found that although the replication timing of double minutes was generally preserved in micronuclei, at times it differed greatly from the timing in the nucleus, which may perturb the expression of the amplified oncogenes. Taken together, these findings uncovered the DNA replication occurring inside micronuclei. PMID- 22086907 TI - Association of the von Hippel-Lindau protein with AUF1 and posttranscriptional regulation of VEGFA mRNA. AB - The von Hippel-Lindau (VHL) tumor suppressor gene product is the recognition component of an E3 ubiquitin ligase and is inactivated in patients with VHL disease and in most sporadic clear-cell renal cell carcinomas (RCC). pVHL controls oxygen-responsive gene expression at the transcriptional and posttranscriptional levels. The VEGFA mRNA contains AU-rich elements (ARE) in the 3'-untranslated region, and mRNA stability or decay is determined through ARE associated RNA-binding factors. We show here that levels of the ARE-binding factor, AUF1, are regulated by pVHL and by hypoxia. pVHL and AUF1 stably associate with each other in cells and AUF1 is a ubiquitylation target of pVHL. AUF1 and another RNA-binding protein, HuR, bind to VEGFA ARE RNA. Ribonucleoprotein (RNP) immunoprecipitations showed that pVHL associates indirectly with VEGFA mRNA through AUF1 and/or HuR, and this complex is associated with VEGFA mRNA decay under normoxic conditions. Under hypoxic conditions pVHL is downregulated, whereas AUF1 and HuR binding to VEGF mRNA is maintained, and this complex is associated with stabilized mRNA. These studies suggest that AUF1 and HuR bind to VEGFA ARE RNA under both normoxic and hypoxic conditions, and that a pVHL-RNP complex determines VEGFA mRNA decay. These studies further implicate the ubiquitin-proteasome system in ARE-mediated RNA degradation. PMID- 22086908 TI - Significance of PELP1 in ER-negative breast cancer metastasis. AB - Breast cancer metastasis is a major clinical problem. The molecular basis of breast cancer progression to metastasis remains poorly understood. PELP1 is an estrogen receptor (ER) coregulator that has been implicated as a proto-oncogene whose expression is deregulated in metastatic breast tumors and whose expression is retained in ER-negative tumors. We examined the mechanism and significance of PELP1-mediated signaling in ER-negative breast cancer progression using two ER negative model cells (MDA-MB-231 and 4T1 cells) that stably express PELP1-shRNA. These model cells had reduced PELP1 expression (75% of endogenous levels) and exhibited less propensity to proliferate in growth assays in vitro. PELP1 downregulation substantially affected migration of ER-negative cells in Boyden chamber and invasion assays. Using mechanistic studies, we found that PELP1 modulated expression of several genes involved in the epithelial mesenchymal transition (EMT), including MMPs, SNAIL, TWIST, and ZEB. In addition, PELP1 knockdown reduced the in vivo metastatic potential of ER-negative breast cancer cells and significantly reduced lung metastatic nodules in a xenograft assay. These results implicate PELP1 as having a role in ER-negative breast cancer metastasis, reveal novel mechanism of coregulator regulation of metastasis via promoting cell motility/EMT by modulating expression of genes, and suggest PELP1 may be a potential therapeutic target for metastatic ER-negative breast cancer. PMID- 22086910 TI - New species of Gondwanamyces from dying Euphorbia trees in South Africa. AB - Gondwanamyces and its Custingophora anamorphs were first described from Protea infructescences in South Africa. Subsequently these unusual fungi were also found on Cecropia in Central America. During an investigation into the decline and death of native Euphorbia trees in South Africa, several fungal isolates resembling the anamorph state of Gondwanamyces were obtained from diseased tissues. In this study these isolates are identified based on morphology and comparisons of DNA sequences. Two previously unknown Gondwanamyces species were identified, both were associated with damage caused by beetles (Cossonus sp.). Inoculation studies showed that the new species of Gondwanamyces are pathogenic on Euphorbia ingens and may contribute to the decline of these trees. PMID- 22086912 TI - Revision of taxonomic concept and systematic position of some Clavariaceae species. AB - A taxonomic and nomenclatural revision of some representatives of Clavariaceae is presented based on extensive collecting in central and western Europe. Five species originally described from Europe are identified, redescribed and delimited: Clavaria fragilis, Ramariopsis crocea, R. corniculata, R. helvola and R. pulchella. Lectotypes, epitypes or neotypes are designated for all these species. Descriptions are based on macro- and micromorphological characters and supplemented with DNA analyses of the nrLSU regions from 20 specimens. The molecular phylogenetic analyses reconstructed a phylogram showing relationships among the discussed species as well as some closely related taxa. The taxonomic value of the ratio of length and width of spores (Q-value) is discussed. PMID- 22086911 TI - Phylogenetic diversity of insecticolous fusaria inferred from multilocus DNA sequence data and their molecular identification via FUSARIUM-ID and Fusarium MLST. AB - We constructed several multilocus DNA sequence datasets to assess the phylogenetic diversity of insecticolous fusaria, especially focusing on those housed at the Agricultural Research Service Collection of Entomopathogenic Fungi (ARSEF), and to aid molecular identifications of unknowns via the FUSARIUM-ID and Fusarium MLST online databases and analysis packages. Analyses of a 190-taxon, two-locus dataset, which included 159 isolates from insects, indicated that: (i) insect-associated fusaria were nested within 10 species complexes spanning the phylogenetic breadth of Fusarium, (ii) novel, putatively unnamed insecticolous species were nested within 8/10 species complexes and (iii) Latin binomials could be applied with confidence to only 18/58 phylogenetically distinct fusaria associated with pest insects. Phylogenetic analyses of an 82-taxon, three-locus dataset nearly fully resolved evolutionary relationships among the 10 clades containing insecticolous fusaria. Multilocus typing of isolates within four species complexes identified surprisingly high genetic diversity in that 63/65 of the fusaria typed represented newly discovered haplotypes. The DNA sequence data, together with corrected ABI sequence chromatograms and alignments, have been uploaded to the following websites dedicated to identifying fusaria: FUSARIUM-ID (http://isolate.fusariumdb.org) at Pennsylvania State University's Department of Plant Pathology and Fusarium MLST (http://www.cbs.knaw.nl/fusarium) at the Centraalbureau voor Schimmelcultures (CBS-KNAW) Fungal Biodiversity Center. PMID- 22086913 TI - Application of the Apn2/MAT locus to improve the systematics of the Colletotrichum gloeosporioides complex: an example from coffee (Coffea spp.) hosts. AB - To improve phylogenetic resolution of the Colletotrichum gloeosporioides species complex we developed and tested the performance of a new set of primers for the Apn2/MAT locus with a case study of 22 isolates. These were isolated mainly from coffee plants and represent six divergent and well characterized species within the C. gloeosporioides complex. Following previous studies on this locus, we have generated sequence data from an expanded region (> 4600 bp), revealing increased phylogenetic informativeness when compared to other commonly used markers such as ITS, beta-tub2 and GS. Within the Apn2/MAT locus the ApMAT marker alone was almost as informative in terms of phylogenetic resolution as a seven-gene concatenated dataset. Our results further revealed that gene-tree discordance may come to be a common issue in resolving evolutionary relationships in the C. gloeosporioides complex, highlighting the importance of multilocus approaches. The use of state-of-the-art data analysis techniques and a highly informative dataset as employed here may abate this issue and hopefully assist in disentangling the C. gloeosporioides complex. PMID- 22086914 TI - Generation and functional characterization of knock-in mice harboring the cardiac troponin I-R21C mutation associated with hypertrophic cardiomyopathy. AB - The R21C substitution in cardiac troponin I (cTnI) is the only identified mutation within its unique N-terminal extension that is associated with hypertrophic cardiomyopathy (HCM) in man. Particularly, this mutation is located in the consensus sequence for beta-adrenergic-activated protein kinase A (PKA) mediated phosphorylation. The mechanisms by which this mutation leads to heart disease are still unclear. Therefore, we generated cTnI knock-in mouse models carrying an R21C mutation to evaluate the resultant functional consequences. Measuring the in vivo levels of incorporated mutant and WT cTnI, and their basal phosphorylation levels by top-down mass spectrometry demonstrated: 1) a dominant negative effect such that, the R21C+/- hearts incorporated 24.9% of the mutant cTnI within the myofilament; and 2) the R21C mutation abolished the in vivo phosphorylation of Ser(23)/Ser(24) in the mutant cTnI. Adult heterozygous (R21C+/ ) and homozygous (R21C+/+) mutant mice activated the fetal gene program and developed a remarkable degree of cardiac hypertrophy and fibrosis. Investigation of cardiac skinned fibers isolated from WT and heterozygous mice revealed that the WT cTnI was completely phosphorylated at Ser(23)/Ser(24) unless the mice were pre-treated with propranolol. After propranolol treatment (-PKA), the pCa-tension relationships of all three mice (i.e. WT, R21C+/-, and R21C+/+) were essentially the same. However, after treatment with propranolol and PKA, the R21C cTnI mutation reduced (R21C+/-) or abolished (R21C+/+) the well known decrease in the Ca(2+) sensitivity of tension that accompanies Ser(23)/Ser(24) cTnI phosphorylation. Altogether, the combined effects of the R21C mutation appear to contribute toward the development of HCM and suggest that another physiological role for the phosphorylation of Ser(23)/Ser(24) in cTnI is to prevent cardiac hypertrophy. PMID- 22086915 TI - CTRP1 protein enhances fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase (ACC) inhibition. AB - We previously described the adipokine CTRP1, which has up-regulated expression following exposure to the anti-diabetic drug rosiglitazone and increased circulating levels in adiponectin-null mice (Wong, G. W., Krawczyk, S. A., Kitidis-Mitrokostas, C., Revett, T., Gimeno, R., and Lodish, H. F. (2008) Biochem. J. 416, 161-177). Although recombinant CTRP1 lowers blood glucose in mice, its physiological function, mechanisms of action, and roles in metabolic stress remain unknown. Here, we show that circulating levels of CTRP1 are strikingly reduced in diet-induced obese mice. Overexpressing CTRP1 in transgenic mice improved insulin sensitivity and decreased high-fat diet-induced weight gain. Reduced adiposity resulted from enhanced fatty acid oxidation and energy expenditure, effects mediated by AMP-activated protein kinase (AMPK). In skeletal muscle of transgenic mice, AMPKalpha and its downstream target, acetyl-CoA carboxylase (ACC), were hyperphosphorylated, indicative of AMPK activation and ACC inhibition. Inactivation of ACC promotes mitochondrial fat oxidation. Consistent with the direct effect of CTRP1 on AMPK signaling, recombinant CTRP1 administration acutely stimulated muscle AMPKalpha and ACC phosphorylation in vivo. In isolated soleus muscle, recombinant CTRP1 activated AMPK signaling to increase fatty acid oxidation ex vivo, an effect abrogated by an AMPK inhibitor. These results provide the first in vivo evidence that CTRP1 is a novel regulator of fatty acid metabolism. PMID- 22086916 TI - Testis-specific miRNA-469 up-regulated in gonadotropin-regulated testicular RNA helicase (GRTH/DDX25)-null mice silences transition protein 2 and protamine 2 messages at sites within coding region: implications of its role in germ cell development. AB - Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), a testis-specific member of the DEAD-box family, is an essential post-transcriptional regulator of spermatogenesis. Failure of expression of Transition protein 2 (TP2) and Protamine 2 (Prm2) proteins (chromatin remodelers, essential for spermatid elongation and completion of spermatogenesis) with preservation of their mRNA expression was observed in GRTH-null mice (azoospermic due to failure of spermatids to elongate). These were identified as target genes for the testis specific miR-469, which is increased in the GRTH-null mice. Further analysis demonstrated that miR-469 repressed TP2 and Prm2 protein expression at the translation level with minor effect on mRNA degradation, through binding to the coding regions of TP2 and Prm2 mRNAs. The corresponding primary-microRNAs and the expression levels of Drosha and DGCR8 (both mRNA and protein) were increased significantly in the GRTH-null mice. miR-469 silencing of TP2 and Prm2 mRNA in pachytene spermatocytes and round spermatids is essential for their timely translation at later times of spermiogenesis, which is critical to attain mature sperm. Collectively, these studies indicate that GRTH, a multifunctional RNA helicase, acts as a negative regulator of miRNA-469 biogenesis and consequently their function during spermatogenesis. PMID- 22086917 TI - Dynamic ligand-induced conformational rearrangements in P-glycoprotein as probed by fluorescence resonance energy transfer spectroscopy. AB - P-glycoprotein (Pgp), a member of the ATP-binding cassette transporter family, functions as an ATP hydrolysis-driven efflux pump to rid the cell of toxic organic compounds, including a variety of drugs used in anticancer chemotherapy. Here, we used fluorescence resonance energy transfer (FRET) spectroscopy to delineate the structural rearrangements the two nucleotide binding domains (NBDs) are undergoing during the catalytic cycle. Pairs of cysteines were introduced into equivalent regions in the N- and C-terminal NBDs for labeling with fluorescent dyes for ensemble and single-molecule FRET spectroscopy. In the ensemble FRET, a decrease of the donor to acceptor (D/A) ratio was observed upon addition of drug and ATP. Vanadate trapping further decreased the D/A ratio, indicating close association of the two NBDs. One of the cysteine mutants was further analyzed using confocal single-molecule FRET spectroscopy. Single Pgp molecules showed fast fluctuations of the FRET efficiencies, indicating movements of the NBDs on a time scale of 10-100 ms. Populations of low, medium, and high FRET efficiencies were observed during drug-stimulated MgATP hydrolysis, suggesting the presence of at least three major conformations of the NBDs during catalysis. Under conditions of vanadate trapping, most molecules displayed high FRET efficiency states, whereas with cyclosporin, more molecules showed low FRET efficiency. Different dwell times of the FRET states were found for the distinct biochemical conditions, with the fastest movements during active turnover. The FRET spectroscopy observations are discussed in context of a model of the catalytic mechanism of Pgp. PMID- 22086918 TI - A Monod-Wyman-Changeux mechanism can explain G protein-coupled receptor (GPCR) allosteric modulation. AB - The Monod-Wyman-Changeux (MWC) model was initially proposed to describe the allosteric properties of regulatory enzymes and subsequently extended to receptors. Yet despite GPCRs representing the largest family of receptors and drug targets, no study has systematically evaluated the MWC mechanism as it applies to GPCR allosteric ligands. We reveal how the recently described allosteric modulator, benzyl quinolone carboxylic acid (BQCA), behaves according to a strict, two-state MWC mechanism at the M1 muscarinic acetylcholine receptor (mAChR). Despite having a low affinity for the M1 mAChR, BQCA demonstrated state dependence, exhibiting high positive cooperativity with orthosteric agonists in a manner that correlated with efficacy but negative cooperativity with inverse agonists. The activity of BQCA was significantly increased at a constitutively active M1 mAChR but abolished at an inactive mutant. Interestingly, BQCA possessed intrinsic signaling efficacy, ranging from near-quiescence to full agonism depending on the coupling efficiency of the chosen intracellular pathway. This latter cellular property also determined the difference in magnitude of positive cooperativity between BQCA and the orthosteric agonist, carbachol, across pathways. The lack of additional, pathway-biased, allosteric modulation by BQCA was confirmed in genetically engineered yeast strains expressing different chimeras between the endogenous yeast G(pa1) protein and human Galpha subunits. These findings define a chemical biological framework that can be applied to the study and classification of allosteric modulators across different GPCR families. PMID- 22086919 TI - Reduced immunoglobulin A transcytosis associated with immunoglobulin A nephropathy and nasopharyngeal carcinoma. AB - Polymeric IgA (pIgA) is transcytosed by the pIgA receptor (pIgR) across mucosal epithelial cells. After transcytosis to the apical surface, the extracellular, ligand-binding portion of the pIgR is proteolytically cleaved. A missense mutation in human pIgR, A580V, is associated with IgA nephropathy and nasopharyngeal carcinoma. We report that this mutation reduces the rate of transcytosis of pIgR and pIgA, and seemingly the rate of pIgR cleavage. We propose that the defects in pIgR trafficking caused by the A580V mutation may underlie the pathogenesis of both diseases. PMID- 22086920 TI - Yeast sterol regulatory element-binding protein (SREBP) cleavage requires Cdc48 and Dsc5, a ubiquitin regulatory X domain-containing subunit of the Golgi Dsc E3 ligase. AB - Schizosaccharomyces pombe Sre1 is a membrane-bound transcription factor that controls adaptation to hypoxia. Like its mammalian homolog, sterol regulatory element-binding protein (SREBP), Sre1 activation requires release from the membrane. However, in fission yeast, this release occurs through a strikingly different mechanism that requires the Golgi Dsc E3 ubiquitin ligase complex and the proteasome. The mechanistic details of Sre1 cleavage, including the link between the Dsc E3 ligase complex and proteasome, are not well understood. Here, we present results of a genetic selection designed to identify additional components required for Sre1 cleavage. From the selection, we identified two new components of the fission yeast SREBP pathway: Dsc5 and Cdc48. The AAA (ATPase associated with diverse cellular activities) ATPase Cdc48 and Dsc5, a ubiquitin regulatory X domain-containing protein, interact with known Dsc complex components and are required for SREBP cleavage. These findings provide a mechanistic link between the Dsc E3 ligase complex and the proteasome in SREBP cleavage and add to a growing list of similarities between the Dsc E3 ligase and membrane E3 ligases involved in endoplasmic reticulum-associated degradation. PMID- 22086921 TI - Neutrons, magnets, and photons: a career in structural biology. AB - The purpose of Reflections articles, it seems, is to give elderly scientists a chance to write about the "good old days," when everyone walked to school in the snow. They enjoy this activity so much that your editor, Martha Fedor, must have known that I would accept her invitation to write such an article, no matter how much I demurred at first. As everyone knows, flattery will get you everywhere. It may comfort the apprehensive reader to learn that there is not going to be much walking to school in the snow in this story. On the contrary, rather than thinking how hard I had it during my scientific career, I find it inconceivable that anyone could have had a smoother ride. At the time I began my career, science was an expanding enterprise in the United States that welcomed the young. Only in such an opportunity-rich environment would someone like me have stood a chance. The contrast between that world and the dog-eat-dog world young scientists confront today is stark. PMID- 22086922 TI - Fructose protects murine hepatocytes from tumor necrosis factor-induced apoptosis by modulating JNK signaling. AB - Fructose-induced hepatic ATP depletion prevents TNF-induced apoptosis, whereas it contrarily enhances CD95-induced hepatocyte apoptosis in vitro and in vivo. By contrast, transformed liver cells are not protected against TNF due to metabolic alterations, allowing selective tumor targeting. We analyzed the molecular mechanisms by which fructose modulates cytokine-induced apoptosis. A release of adenosine after fructose-induced ATP depletion, followed by a cAMP response, was demonstrated. Likewise, cAMP and adenosine mimicked per se the modulation by fructose of CD95- and TNF-induced apoptosis. The effects of fructose on cytokine induced apoptosis were sensitive to inhibition of protein kinase A. Fructose prevented the pro-apoptotic, sustained phase of TNF-induced JNK signaling and thereby blocked bid-mediated activation of the intrinsic mitochondrial apoptosis pathway in a PKA-dependent manner. We explain the dichotomal effects of fructose on CD95- and TNF-induced cell death by the selective requirement of JNK signaling for the latter. These findings provide a mechanistic rationale for the protection of hepatocytes from TNF-induced cell death by pharmacological doses of fructose. PMID- 22086923 TI - Angiotensin II increases activity of the epithelial Na+ channel (ENaC) in distal nephron additively to aldosterone. AB - Dietary salt intake controls epithelial Na+ channel (ENaC)-mediated Na+ reabsorption in the distal nephron by affecting status of the renin-angiotensin aldosterone system (RAAS). Whereas regulation of ENaC by aldosterone is generally accepted, little is known about whether other components of RAAS, such as angiotensin II (Ang II), have nonredundant to aldosterone-stimulatory actions on ENaC. We combined patch clamp electrophysiology and immunohistochemistry in freshly isolated split-opened distal nephrons of mice to determine the mechanism and molecular signaling pathway of Ang II regulation of ENaC. We found that Ang II acutely increases ENaC Po, whereas prolonged exposure to Ang II also induces translocation of alpha-ENaC toward the apical membrane in situ. Ang II actions on ENaC Po persist in the presence of saturated mineralocorticoid status. Moreover, aldosterone fails to stimulate ENaC acutely, suggesting that Ang II and aldosterone have different time frames of ENaC activation. AT1 but not AT2 receptors mediate Ang II actions on ENaC. Unlike its effect in vasculature, Ang II did not increase [Ca2+]i in split-opened distal nephrons as demonstrated using ratiometric Fura-2-based microscopy. However, application of Ang II to mpkCCDc14 cells resulted in generation of reactive oxygen species, as probed with fluorescent methods. Consistently, inhibiting NADPH oxidase with apocynin abolished Ang II-mediated increases in ENaC Po in murine distal nephron. Therefore, we concluded that Ang II directly regulates ENaC activity in the distal nephron, and this effect complements regulation of ENaC by aldosterone. We propose that stimulation of AT1 receptors with subsequent activation of NADPH oxidase signaling pathway mediates Ang II actions on ENaC. PMID- 22086924 TI - Sulfiredoxin protein is critical for redox balance and survival of cells exposed to low steady-state levels of H2O2. AB - Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of cysteine sulfinic acid of hyperoxidized peroxiredoxins (Prxs). Having high affinity toward H2O2, 2 Cys Prxs can efficiently reduce H2O2 at low concentration. We previously showed that Prx I is hyperoxidized at a rate of 0.072% per turnover even in the presence of low steady-state levels of H2O2. Here we examine the novel role of Srx in cells exposed to low steady-state levels of H2O2, which can be achieved by using glucose oxidase. Exposure of low steady-state levels of H2O2 (10-20 MUm) to A549 or wild-type mouse embryonic fibroblast (MEF) cells does not lead to any significant change in oxidative injury because of the maintenance of balance between H2O2 production and elimination. In contrast, loss-of-function studies using Srx-depleted A549 and Srx-/- MEF cells demonstrate a dramatic increase in extra- and intracellular H2O2, sulfinic 2-Cys Prxs, and apoptosis. Concomitant with hyperoxidation of mitochondrial Prx III, Srx-depleted cells show an activation of mitochondria-mediated apoptotic pathways including mitochondria membrane potential collapse, cytochrome c release, and caspase activation. Furthermore, adenoviral re-expression of Srx in Srx-depleted A549 or Srx-/- MEF cells promotes the reactivation of sulfinic 2-Cys Prxs and results in cellular resistance to apoptosis, with enhanced removal of H2O2. These results indicate that Srx functions as a novel component to maintain the balance between H2O2 production and elimination and then protects cells from apoptosis even in the presence of low steady-state levels of H2O2. PMID- 22086925 TI - Wogonin and related natural flavones overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein resistance of tumors by down-regulation of c-FLIP protein and up-regulation of TRAIL receptor 2 expression. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that kills various tumor cells without damaging normal tissues. However, many cancers remain resistant to TRAIL. To overcome TRAIL resistance, combination therapies using sensitizers of the TRAIL pathway would be an efficacious approach. To investigate potential sensitizers of TRAIL-induced apoptosis, we used TRAIL-resistant human T cell leukemia virus type 1 (HTLV-1) associated adult T cell leukemia/lymphoma (ATL) cells as a model system. So far, HTLV-1-associated ATL is incurable by presently known therapies. Here, we show that wogonin and the structurally related natural flavones apigenin and chrysin break TRAIL resistance in HTLV-1-associated ATL by transcriptional down regulation of c-FLIP, a key inhibitor of death receptor signaling, and by up regulation of TRAIL receptor 2 (TRAIL-R2). This effect is mediated through transcriptional inhibition of the p53 antagonist murine double minute 2 (Mdm2), leading to an increase in p53 levels and, consequently, to up-regulation of the p53 target gene TRAIL-R2. We also show that these flavones can sensitize to TNFalpha- and CD95-mediated cell death. Furthermore, we show that wogonin, apigenin, and chrysin also enhance TRAIL-mediated apoptosis in other human cancer cell lines including breast cancer cell line MDA-MB-231, colon cancer cell line HT-29, hepatocellular carcinoma cell line HepG2, melanoma cell line SK-MEL-37, and pancreatic carcinoma cell line Capan-1 by the same mechanism. Thus, our study suggests the potential use of these flavones as an adjuvant for TRAIL-mediated anticancer therapy. PMID- 22086926 TI - Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid beta production by altering Nicastrin maturation and intracellular localization. AB - Clinical, pharmacological, biochemical, and genetic evidence support the notion that alteration of cholesterol homeostasis strongly predisposes to Alzheimer disease (AD). The ATP-binding cassette transporter-2 (Abca2), which plays a role in intracellular sterol trafficking, has been genetically linked to AD. It is unclear how these two processes are related. Here we demonstrate that down regulation of Abca2 in mammalian cells leads to decreased amyloid-beta (Abeta) generation. In vitro studies revealed altered gamma-secretase complex formation in Abca2 knock-out cells due to the altered levels, post-translational modification, and subcellular localization of Nicastrin. Reduced Abca2 levels in mammalian cells in vitro, in Drosophila melanogaster and in mice resulted in altered gamma-secretase processing of APP, and thus Abeta generation, without affecting Notch cleavage. PMID- 22086927 TI - Thromboxane receptor signaling is required for fibronectin-induced matrix metalloproteinase 9 production by human and murine macrophages and is attenuated by the Arhgef1 molecule. AB - During an inflammatory response, resident and newly recruited tissue macrophages adhere to extracellular matrix and cell-bound integrin ligands. This interaction induces the expression of pro-inflammatory mediators that include matrix metalloproteinases (MMPs). Arhgef1 is an intracellular signaling molecule expressed by myeloid cells that normally attenuates murine macrophage MMP production in vivo and in vitro after cell culture on the extracellular matrix protein, fibronectin. In this study, we have extended the characterization of this fibronectin-induced Arhgef1-regulated signaling pathway in both human and murine myeloid cells. Our results show that MMP9 production by fibronectin stimulated monocytes and macrophages depends on autocrine thromboxane receptor signaling and that under normal conditions, this signaling pathway is attenuated by Arhgef1. Finally, we show that the expression of ARHGEF1 by human peripheral blood monocytes varies between individuals and inversely correlates with fibronectin-mediated MMP9 production. PMID- 22086928 TI - Diversity in the C3b [corrected] contact residues and tertiary structures of the staphylococcal complement inhibitor (SCIN) protein family. AB - To survive in immune-competent hosts, the pathogen Staphylococcus aureus expresses and secretes a sophisticated array of proteins that inhibit the complement system. Among these are the staphylococcal complement inhibitors (SCIN), which are composed of three active proteins (SCIN-A, -B, and -C) and one purportedly inactive member (SCIN-D or ORF-D). Because previous work has focused almost exclusively on SCIN-A, we sought to provide initial structure/function information on additional SCIN proteins. To this end we determined crystal structures of an active, N-terminal truncation mutant of SCIN-B (denoted SCIN-B18 85) both free and bound to the C3c fragment of complement component C3 at 1.5 and 3.4 A resolution, respectively. Comparison of the C3c/SCIN-B18-85 structure with that of C3c/SCIN-A revealed that both proteins target the same functional hotspot on the C3b/C3c surface yet harbor diversity in both the type of residues and interactions formed at their C3b/C3c interfaces. Most importantly, these structures allowed identification of Arg44 and Tyr51 as residues key for SCIN-B binding to C3b and subsequent inhibition of the AP C3 convertase. In addition, we also solved several crystal structures of SCIN-D to 1.3 A limiting resolution. This revealed an unexpected structural deviation in the N-terminal alpha helix relative to SCIN-A and SCIN-B. Comparative analysis of both electrostatic potentials and surface complementarity suggest a physical explanation for the inability of SCIN-D to bind C3b/C3c. Together, these studies provide a more thorough understanding of immune evasion by S. aureus and enhance potential use of SCIN proteins as templates for design of complement targeted therapeutics. PMID- 22086929 TI - Xenopus laevis Ctc1-Stn1-Ten1 (xCST) protein complex is involved in priming DNA synthesis on single-stranded DNA template in Xenopus egg extract. AB - The Ctc1-Stn1-Ten1 (CST) complex is an RPA (replication protein A)-like protein complex that binds to single-stranded (ss) DNA. It localizes at telomeres and is involved in telomere end protection in mammals and plants. It is also known to stimulate DNA polymerase alpha-primase in vitro. However, it is not known how CST accomplishes these functions in vivo. Here, we report the identification and characterization of Xenopus laevis CST complex (xCST). xCST showed ssDNA binding activity with moderate preference for G (guanine)-rich sequences. xStn1 immunodepleted Xenopus egg extracts supported chromosomal DNA replication in in vitro reconstituted sperm nuclei, suggesting that xCST is not a general replication factor. However, the immunodepletion or neutralization of xStn1 compromised DNA synthesis on ssDNA template. Because primed ssDNA template was replicated in xStn1-immunodepleted extracts as efficiently as in control ones, we conclude that xCST is involved in the priming step on ssDNA template. These results are consistent with the current model that CST is involved in telomeric C strand synthesis through the regulation of DNA polymerase alpha-primase. PMID- 22086930 TI - The power of being present: the value of mindfulness interventions in improving health and well-being. PMID- 22086941 TI - Microvascular obstruction is caused by atherothrombosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention. PMID- 22086943 TI - Cardiac magnetic resonance assessment of myocardial fibrosis: honing new clinical tools. PMID- 22086942 TI - Perfusion imaging with vasodilator stress echocardiography: a physiologically sound approach to coronary disease? PMID- 22086944 TI - Absolute quantification of myocardial perfusion: a method proves its mettle. PMID- 22086945 TI - Ischemic burden, treatment allocation, and outcomes in stable coronary artery disease. PMID- 22086948 TI - MetaCrop 2.0: managing and exploring information about crop plant metabolism. AB - MetaCrop is a manually curated repository of high-quality data about plant metabolism, providing different levels of detail from overview maps of primary metabolism to kinetic data of enzymes. It contains information about seven major crop plants with high agronomical importance and two model plants. MetaCrop is intended to support research aimed at the improvement of crops for both nutrition and industrial use. It can be accessed via web, web services and an add-on to the Vanted software. Here, we present several novel developments of the MetaCrop system and the extended database content. MetaCrop is now available in version 2.0 at http://metacrop.ipk-gatersleben.de. PMID- 22086949 TI - doRiNA: a database of RNA interactions in post-transcriptional regulation. AB - In animals, RNA binding proteins (RBPs) and microRNAs (miRNAs) post transcriptionally regulate the expression of virtually all genes by binding to RNA. Recent advances in experimental and computational methods facilitate transcriptome-wide mapping of these interactions. It is thought that the combinatorial action of RBPs and miRNAs on target mRNAs form a post transcriptional regulatory code. We provide a database that supports the quest for deciphering this regulatory code. Within doRiNA, we are systematically curating, storing and integrating binding site data for RBPs and miRNAs. Users are free to take a target (mRNA) or regulator (RBP and/or miRNA) centric view on the data. We have implemented a database framework with short query response times for complex searches (e.g. asking for all targets of a particular combination of regulators). All search results can be browsed, inspected and analyzed in conjunction with a huge selection of other genome-wide data, because our database is directly linked to a local copy of the UCSC genome browser. At the time of writing, doRiNA encompasses RBP data for the human, mouse and worm genomes. For computational miRNA target site predictions, we provide an update of PicTar predictions. PMID- 22086950 TI - MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. AB - Peptidases, their substrates and inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database (http://merops.sanger.ac.uk) aims to fulfil the need for an integrated source of information about these. The database has hierarchical classifications in which homologous sets of peptidases and protein inhibitors are grouped into protein species, which are grouped into families, which are in turn grouped into clans. The database has been expanded to include proteolytic enzymes other than peptidases. Special identifiers for peptidases from a variety of model organisms have been established so that orthologues can be detected in other species. A table of predicted active-site residue and metal ligand positions and the residue ranges of the peptidase domains in orthologues has been added to each peptidase summary. New displays of tertiary structures, which can be rotated or have the surfaces displayed, have been added to the structure pages. New indexes for gene names and peptidase substrates have been made available. Among the enhancements to existing features are the inclusion of small-molecule inhibitors in the tables of peptidase inhibitor interactions, a table of known cleavage sites for each protein substrate, and tables showing the substrate-binding preferences of peptidases derived from combinatorial peptide substrate libraries. PMID- 22086951 TI - The UCSC Genome Browser database: extensions and updates 2011. AB - The University of California Santa Cruz Genome Browser (http://genome.ucsc.edu) offers online public access to a growing database of genomic sequence and annotations for a wide variety of organisms. The Browser is an integrated tool set for visualizing, comparing, analyzing and sharing both publicly available and user-generated genomic data sets. In the past year, the local database has been updated with four new species assemblies, and we anticipate another four will be released by the end of 2011. Further, a large number of annotation tracks have been either added, updated by contributors, or remapped to the latest human reference genome. Among these are new phenotype and disease annotations, UCSC genes, and a major dbSNP update, which required new visualization methods. Growing beyond the local database, this year we have introduced 'track data hubs', which allow the Genome Browser to provide access to remotely located sets of annotations. This feature is designed to significantly extend the number and variety of annotation tracks that are publicly available for visualization and analysis from within our site. We have also introduced several usability features including track search and a context-sensitive menu of options available with a right-click anywhere on the Browser's image. PMID- 22086952 TI - Increased in vivo inhibition of gene expression by combining RNA interference and U1 inhibition. AB - Inhibition of gene expression can be achieved with RNA interference (RNAi) or U1 small nuclear RNA-snRNA-interference (U1i). U1i is based on U1 inhibitors (U1in), U1 snRNA molecules modified to inhibit polyadenylation of a target pre-mRNA. In culture, we have shown that the combination of RNAi and U1i results in stronger inhibition of reporter or endogenous genes than that obtained using either of the techniques alone. We have now used these techniques to inhibit gene expression in mice. We show that U1ins can induce strong inhibition of the expression of target genes in vivo. Furthermore, combining U1i and RNAi results in synergistic inhibitions also in mice. This is shown for the inhibition of hepatitis B virus (HBV) sequences or endogenous Notch1. Surprisingly, inhibition obtained by combining a U1in and a RNAi mediator is higher than that obtained by combining two U1ins or two RNAi mediators. Our results suggest that RNAi and U1i cooperate by unknown mechanisms to result in synergistic inhibitions. Analysis of toxicity and specificity indicates that expression of U1i inhibitors is safe. Therefore, we believe that the combination of RNAi and U1i will be a good option to block damaging endogenous genes, HBV and other infectious agents in vivo. PMID- 22086953 TI - IMG/M: the integrated metagenome data management and comparative analysis system. AB - The integrated microbial genomes and metagenomes (IMG/M) system provides support for comparative analysis of microbial community aggregate genomes (metagenomes) in a comprehensive integrated context. IMG/M integrates metagenome data sets with isolate microbial genomes from the IMG system. IMG/M's data content and analytical capabilities have been extended through regular updates since its first release in 2007. IMG/M is available at http://img.jgi.doe.gov/m. A companion IMG/M systems provide support for annotation and expert review of unpublished metagenomic data sets (IMG/M ER: http://img.jgi.doe.gov/mer). PMID- 22086954 TI - The 19S proteasome subcomplex promotes the targeting of NuA4 HAT to the promoters of ribosomal protein genes to facilitate the recruitment of TFIID for transcriptional initiation in vivo. AB - Previous studies have implicated SAGA (Spt-Ada-Gcn5-acetyltransferase) and TFIID (Transcription factor-IID)-dependent mechanisms of transcriptional activation in yeast. SAGA-dependent transcriptional activation is further regulated by the 19S proteasome subcomplex. However, the role of the 19S proteasome subcomplex in transcriptional activation of the TFIID-dependent genes has not been elucidated. Therefore, we have performed a series of chromatin immunoprecipitation, mutational and transcriptional analyses at the TFIID-dependent ribosomal protein genes such as RPS5, RPL2B and RPS11B. We find that the 19S proteasome subcomplex is recruited to the promoters of these ribosomal protein genes, and promotes the association of NuA4 (Nucleosome acetyltransferase of histone H4) co-activator, but not activator Rap1p (repressor-activator protein 1). These observations support that the 19S proteasome subcomplex enhances the targeting of co-activator at the TFIID-dependent promoter. Such an enhanced targeting of NuA4 HAT (histone acetyltransferase) promotes the recruitment of the TFIID complex for transcriptional initiation. Collectively, our data demonstrate that the 19S proteasome subcomplex enhances the targeting of NuA4 HAT to activator Rap1p at the promoters of ribosomal protein genes to facilitate the recruitment of TFIID for transcriptional stimulation, hence providing a new role of the 19S proteasome subcomplex in establishing a specific regulatory network at the TFIID-dependent promoter for productive transcriptional initiation in vivo. PMID- 22086955 TI - Pre-B cell to macrophage transdifferentiation without significant promoter DNA methylation changes. AB - Transcription factor-induced lineage reprogramming or transdifferentiation experiments are essential for understanding the plasticity of differentiated cells. These experiments helped to define the specific role of transcription factors in conferring cell identity and played a key role in the development of the regenerative medicine field. We here investigated the acquisition of DNA methylation changes during C/EBPalpha-induced pre-B cell to macrophage transdifferentiation. Unexpectedly, cell lineage conversion occurred without significant changes in DNA methylation not only in key B cell- and macrophage specific genes but also throughout the entire set of genes differentially methylated between the two parental cell types. In contrast, active and repressive histone modification marks changed according to the expression levels of these genes. We also demonstrated that C/EBPalpha and RNA Pol II are associated with the methylated promoters of macrophage-specific genes in reprogrammed macrophages without inducing methylation changes. Our findings not only provide insights about the extent and hierarchy of epigenetic events in pre B cell to macrophage transdifferentiation but also show an important difference to reprogramming towards pluripotency where promoter DNA demethylation plays a pivotal role. PMID- 22086956 TI - The SEQanswers wiki: a wiki database of tools for high-throughput sequencing analysis. AB - Recent advances in sequencing technology have created unprecedented opportunities for biological research. However, the increasing throughput of these technologies has created many challenges for data management and analysis. As the demand for sophisticated analyses increases, the development time of software and algorithms is outpacing the speed of traditional publication. As technologies continue to be developed, methods change rapidly, making publications less relevant for users. The SEQanswers wiki (SEQwiki) is a wiki database that is actively edited and updated by the members of the SEQanswers community (http://SEQanswers.com/). The wiki provides an extensive catalogue of tools, technologies and tutorials for high-throughput sequencing (HTS), including information about HTS service providers. It has been implemented in MediaWiki with the Semantic MediaWiki and Semantic Forms extensions to collect structured data, providing powerful navigation and reporting features. Within 2 years, the community has created pages for over 500 tools, with approximately 400 literature references and 600 web links. This collaborative effort has made SEQwiki the most comprehensive database of HTS tools anywhere on the web. The wiki includes task-focused mini reviews of commonly used tools, and a growing collection of more than 100 HTS service providers. SEQwiki is available at: http://wiki.SEQanswers.com/. PMID- 22086957 TI - Do replication forks control late origin firing in Saccharomyces cerevisiae? AB - Recent studies of eukaryotic DNA replication timing profiles suggest that the time-dependent rate of origin firing, I(t), has a universal shape, which ensures a reproducible replication completion time. However, measurements of I(t) are based on population averages, which may bias the shape of the I(t) because of imperfect cell synchrony and cell-to-cell variability. Here, we measure the population-averaged I(t) profile from synchronized Saccharomyces cerevisiae cells using DNA combing and we extract the single-cell I(t) profile using numerical deconvolution. The single cell I(t) and the population-averaged I(t) extracted from DNA combing and replication timing profiles are similar, indicating a genome scale invariance of the replication process, and excluding cell-to-cell variability in replication time as an explanation for the shape of I(t). The single cell I(t) correlates with fork density in wild-type cells, which is specifically loosened in late S phase in the clb5Delta mutant. A previously proposed numerical model that reproduces the wild-type I(t) profile, could also describe the clb5Delta mutant I(t) once modified to incorporate the decline in CDK activity and the looser dependency of initiation on fork density in the absence of Clb5p. Overall, these results suggest that the replication forks emanating from early fired origins facilitate origin firing in later-replicating regions. PMID- 22086958 TI - DBTSS: DataBase of Transcriptional Start Sites progress report in 2012. AB - To support transcriptional regulation studies, we have constructed DBTSS (DataBase of Transcriptional Start Sites), which contains exact positions of transcriptional start sites (TSSs), determined with our own technique named TSS seq, in the genomes of various species. In its latest version, DBTSS covers the data of the majority of human adult and embryonic tissues: it now contains 418 million TSS tag sequences from 28 tissues/cell cultures. Moreover, we integrated a series of our own transcriptomic data, such as the RNA-seq data of subcellular fractionated RNAs as well as the ChIP-seq data of histone modifications and the binding of RNA polymerase II/several transcription factors in cultured cell lines into our original TSS information. We also included several external epigenomic data, such as the chromatin map of the ENCODE project. We further associated our TSS information with public or original single-nucleotide variation (SNV) data, in order to identify SNVs in the regulatory regions. These data can be browsed in our new viewer, which supports versatile search conditions of users. We believe that our new DBTSS will be an invaluable resource for interpreting the differential uses of TSSs and for identifying human genetic variations that are associated with disordered transcriptional regulation. DBTSS can be accessed at http://dbtss.hgc.jp. PMID- 22086959 TI - Development of a 'clickable' non-natural nucleotide to visualize the replication of non-instructional DNA lesions. AB - The misreplication of damaged DNA is an important biological process that produces numerous adverse effects on human health. This report describes the synthesis and characterization of a non-natural nucleotide, designated 3-ethynyl 5-nitroindolyl-2'-deoxyriboside triphosphate (3-Eth-5-NITP), as a novel chemical reagent that can probe and quantify the misreplication of damaged DNA. We demonstrate that this non-natural nucleotide is efficiently inserted opposite an abasic site, a commonly formed and potentially mutagenic non-instructional DNA lesion. The strategic placement of the ethynyl moiety allows the incorporated nucleoside triphosphate to be selectively tagged with an azide-containing fluorophore using 'click' chemistry. This reaction provides a facile way to quantify the extent of nucleotide incorporation opposite non-instructional DNA lesions. In addition, the incorporation of 3-Eth-5-NITP is highly selective for an abasic site, and occurs even in the presence of a 50-fold molar excess of natural nucleotides. The biological applications of using 3-Eth-5-NITP as a chemical probe to monitor and quantify the misreplication of non-instructional DNA lesions are discussed. PMID- 22086960 TI - PrimerBank: a PCR primer database for quantitative gene expression analysis, 2012 update. AB - Optimization of primer sequences for polymerase chain reaction (PCR) and quantitative PCR (qPCR) and reaction conditions remains an experimental challenge. We have developed a resource, PrimerBank, which contains primers that can be used for PCR and qPCR under stringent and allele-invariant amplification conditions. A distinguishing feature of PrimerBank is the experimental validation of primer pairs covering most known mouse genes. Here, we describe a major update of PrimerBank that includes the design of new primers covering 17,076 and 18,086 genes for the human and mouse species, respectively. As a result of this update, PrimerBank contains 497,156 primers (an increase of 62% from the previous version) that cover 36,928 human and mouse genes, corresponding to around 94% of all known protein-coding gene sequences. An updated algorithm based on our previous approach was used to design new primers using current genomic information available from the National Center for Biotechnology Information (NCBI). PrimerBank primers work under uniform PCR conditions, and can be used for high-throughput or genome-wide qPCR. Because of their broader linear dynamic range and greater sensitivity, qPCR approaches are used to reanalyze changes in expression suggested by exploratory technologies such as microarrays and RNA-Seq. The primers and all experimental validation data can be freely accessed from the PrimerBank website, http://pga.mgh.harvard.edu/primerbank/. PMID- 22086961 TI - Direct, genome-wide assessment of DNA mutations in single cells. AB - DNA mutations are the inevitable consequences of errors that arise during replication and repair of DNA damage. Because of their random and infrequent occurrence, quantification and characterization of DNA mutations in the genome of somatic cells has been difficult. Random, low-abundance mutations are currently inaccessible by standard high-throughput sequencing approaches because they cannot be distinguished from sequencing errors. One way to circumvent this problem and simultaneously account for the mutational heterogeneity within tissues is whole genome sequencing of a representative number of single cells. Here, we show elevated mutation levels in single cells from Drosophila melanogaster S2 and mouse embryonic fibroblast populations after treatment with the powerful mutagen N-ethyl-N-nitrosourea. This method can be applied as a direct measure of exposure to mutagenic agents and for assessing genotypic heterogeneity within tissues or cell populations. PMID- 22086962 TI - Helix-length compensation studies reveal the adaptability of the VS ribozyme architecture. AB - Compensatory mutations in RNA are generally regarded as those that maintain base pairing, and their identification forms the basis of phylogenetic predictions of RNA secondary structure. However, other types of compensatory mutations can provide higher-order structural and evolutionary information. Here, we present a helix-length compensation study for investigating structure-function relationships in RNA. The approach is demonstrated for stem-loop I and stem-loop V of the Neurospora VS ribozyme, which form a kissing-loop interaction important for substrate recognition. To rapidly characterize the substrate specificity (k(cat)/K(M)) of several substrate/ribozyme pairs, a procedure was established for simultaneous kinetic characterization of multiple substrates. Several active substrate/ribozyme pairs were identified, indicating the presence of limited substrate promiscuity for stem Ib variants and helix-length compensation between stems Ib and V. 3D models of the I/V interaction were generated that are compatible with the kinetic data. These models further illustrate the adaptability of the VS ribozyme architecture for substrate cleavage and provide global structural information on the I/V kissing-loop interaction. By exploring higher-order compensatory mutations in RNA our approach brings a deeper understanding of the adaptability of RNA structure, while opening new avenues for RNA research. PMID- 22086964 TI - Solid recovered fuels in the steel industry. AB - By using waste materials as alternative fuels in metallurgical plants it is possible to minimize the traditionally used reducing agents, such as coke, coal, oil or natural gas. Moreover, by using waste materials in the metallurgical industry it is feasible to recover these materials as far as possible. This also represents another step towards environmental protection because carbon dioxide emissions can be reduced, if the H(2) content of the waste material is greater in comparison with that of the substituted fuel and the effects of global warming can therefore be reduced. In the present article various solid recovered fuels and their applications in the metallurgical industry are detailed. PMID- 22086965 TI - Perceived barriers in the outdoor environment and development of walking difficulties in older people. PMID- 22086963 TI - Ensembl 2012. AB - The Ensembl project (http://www.ensembl.org) provides genome resources for chordate genomes with a particular focus on human genome data as well as data for key model organisms such as mouse, rat and zebrafish. Five additional species were added in the last year including gibbon (Nomascus leucogenys) and Tasmanian devil (Sarcophilus harrisii) bringing the total number of supported species to 61 as of Ensembl release 64 (September 2011). Of these, 55 species appear on the main Ensembl website and six species are provided on the Ensembl preview site (Pre!Ensembl; http://pre.ensembl.org) with preliminary support. The past year has also seen improvements across the project. PMID- 22086966 TI - Markers of inflammatory status are associated with hearing threshold in older people: findings from the Hertfordshire Ageing Study. AB - BACKGROUND: Age-related hearing loss is a common disabling condition but its causes are not well understood and the role of inflammation as an influencing factor has received little consideration in the literature. OBJECTIVE: To investigate the association between inflammatory markers and hearing in community dwelling older men and women. DESIGN: Cross-sectional analysis within a cohort study. SETTING: The Hertfordshire Ageing Study. PARTICIPANTS: A total of 343 men and 268 women aged 63-74 years on whom data on audiometric testing, inflammatory markers and covariates were available at follow-up in 1995. MAIN OUTCOME MEASURES: Average hearing threshold level (across 500-4,000 Hz) of the worst hearing ear and audiometric slope in dB/octave from 500 to 4,000 Hz. RESULTS: Older age, smoking, history of noise exposure and male gender (all P < 0.001) were associated with higher mean hearing threshold in the worse ear in univariate analysis. After adjustment for these factors in multiple regression models, four measures of immune or inflammatory status were significantly associated with hearing threshold, namely white blood cell count (r = 0.13, P = 0.001), neutrophil count (r = 0.13, P = 0.002), IL-6 (r = 0.10, P = 0.05) and C-reactive protein (r = 0.11, P = 0.01). None of the inflammatory markers was associated with maximum audiometric slope in adjusted analyses. CONCLUSIONS: Markers of inflammatory status were significantly associated with degree of hearing loss in older people. The findings are consistent with the possibility that inflammatory changes occurring with ageing may be involved in age-related hearing loss. Longitudinal data would enable this hypothesis to be explored further. PMID- 22086967 TI - Intelligence across childhood in relation to illegal drug use in adulthood: 1970 British Cohort Study. AB - BACKGROUND: Recent reports have linked high childhood IQ scores with excess alcohol intake and alcohol dependency in adult life, but the relationship with illegal drug use in later life is relatively unknown. METHODS: The authors used data from a large population-based birth cohort (1970 British Cohort Study) with measures of lifetime cannabis and cocaine use, parental social class and psychological distress at 16 years; cannabis, cocaine, amphetamine, ecstasy and polydrug use (more than three drugs) in the past 12 months; and social class, educational attainment and gross monthly income at 30 years. All members of the cohort with IQ scores at 5 or 10 years were eligible to be included in the analyses. RESULTS: Of the 11603 (at 5 years) and 11397 (at 10 years) cohort members eligible, 7904 (68.1%) and 7946 (69.7%) were included in the analyses. IQ scores at 5 years were positively associated with cannabis (OR ((bottom vs top tertile)) =2.25, 95% CI 1.71 to 2.97) and cocaine use (OR 2.35, 95% CI 1.41 to 3.92) in women and with amphetamines (OR 1.46, 95% CI 1.03 to 2.06), ecstasy (OR 1.65, 95% CI 1.15 to 2.36) and polydrug use (OR 1.57, 95% CI 1.09 to 2.26) in men at 30 years. IQ scores at 10 years were positively associated with cannabis, cocaine (only at 30 years), ecstasy, amphetamine and polydrug use. Associations were stronger in women than in men and were independent from psychological distress in adolescence and life-course socioeconomic position. CONCLUSION: High childhood IQ may increase the risk of illegal drug use in adolescence and adulthood. PMID- 22086968 TI - Emerging biomarkers in heart failure. AB - BACKGROUND: Until recently, biomarker testing in heart failure (HF) syndromes has been viewed as an elective supplement to diagnostic evaluation of patients suspected to suffer from this condition. This approach to the use of biomarker testing contrasts with other cardiovascular diagnoses such as acute myocardial infarction, for which biomarkers are integral to disease process definition, risk stratification, and in some cases treatment decision making. CONTENT: In this review we consider various perspectives on the evaluation of biomarkers in HF. In addition, we examine recent advances in the understanding of established biomarkers in HF (such as the natriuretic peptides), the elucidation of novel biomarkers potentially useful for the evaluation and management of patients with HF, and the growing understanding of important and relevant comorbidities in HF. We also review candidate biomarkers from a number of classes: (a) myocyte stretch, (b) myocyte necrosis, (c) systemic inflammation, (d) oxidative stress, (e) extracellular matrix turnover, (f) neurohormones, and (g) biomarkers of extracardiac processes, such as renal function. SUMMARY: Novel applications of established biomarkers of HF as well as elucidation and validation of emerging assays for HF syndromes have collectively led to a growing interest in the more widespread use of such testing in patients affected by the diagnosis. PMID- 22086969 TI - A novel technology for measuring cumulative cardiac biomarker exposure over time: what happened when we weren't looking? PMID- 22086970 TI - Use of natriuretic peptides to guide and monitor heart failure therapy. AB - BACKGROUND: Plasma B-type cardiac natriuretic peptides reflect cardiac structure and function and have proven roles in assisting in the diagnosis of acute heart failure. They are independent prognostic indicators across the full spectrum of cardiovascular disease. Serial changes in plasma B-type cardiac natriuretic peptides parallel prognosis in chronic heart failure. Beneficial responses to medications and devices used in the treatment of heart failure are associated with decreases in plasma B-type peptide concentrations. This effect has led to the hypothesis that intensified treatment directed at reducing B-peptide concentrations may improve outcomes in heart failure. CONTENT: The efficacy of serial measurements of plasma B-type peptides in guiding titration of therapy for chronic heart failure has been the subject of several randomized controlled trials reported in the peer-reviewed literature since 2000. These reports are summarized in this review. Trial design, characteristics of the heart-failure population studied, duration of follow-up, exact end points recorded, and target peptide concentrations pursued all differ somewhat between trials. In addition, in studies in which benefits were seen, the exact mechanisms mediating the improvements in outcome were unclear. However, an overall consistency is emerging that is supported by 2 metaanalyses. SUMMARY: In aggregate the existing trial data suggest that adjustment of treatment in chronic heart failure according to serial B-type peptide measurements, used in conjunction with established clinical methods, is likely to reduce cardiac mortality and hospital admissions with heart failure, at least in patients with systolic heart failure who are younger than 75 years and relatively free of comorbidities. PMID- 22086971 TI - Relaxin ameliorates salt-sensitive hypertension and renal fibrosis. AB - BACKGROUND: Although relaxin (RLX) has potent vasodilatory and anti-fibrotic properties, there is no information on its effects on salt-sensitive hypertension. METHODS: We investigated the effects of short-term treatment with RLX on blood pressure (BP) and nitric oxide synthase (NOS) protein in the kidneys of male Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats after 1 week consumption of an 8% NaCl diet. We also evaluated the inhibitory effects of each specific NOS inhibitor on BP during 1-week RLX treatment under high-salt diet. Next, we examined the long-term effects of RLX treatment for 6 weeks on renal histology and transforming growth factor-beta1 (TGF-beta1) expression in male DS and DR rats placed on the 8-week high-salt diet. RESULTS: The short-term RLX treatment significantly attenuated the high-salt diet-induced rise in BP in DS rats with increasing neuronal NOS and endothelial NOS protein in kidneys. Selective inhibition of each of the three NOS isoforms significantly blocked the anti-hypertensive effects of RLX in DS rats after 1-week high-salt diet. The long term treatment of DS rats with RLX for 6 weeks significantly reduced systolic BP, lessened glomerular and tubulointerstitial changes and reduced TGF-beta signaling compared to saline-treated controls. CONCLUSIONS: The results suggested that RLX converted salt sensitivity to salt resistance, at least in part, by up-regulating NOS. RLX is a potentially useful therapeutic agent for salt-sensitive hypertension. PMID- 22086972 TI - Anti-A/B antibody depletion by semiselective versus ABO blood group-specific immunoadsorption. AB - BACKGROUND: Recipient desensitization using blood group (BG)-specific immunoadsorption (ABO-IA) has proven to enable successful kidney transplantation across major ABO barriers. In this context, the efficiency of non-antigen specific (semiselective) IA adsorbers has not yet been established. The objective of our study was to quantify anti-A/B antibody depletion by protein A-, peptide ligand- and anti-human immunoglobulin-based semiselective IA in comparison to ABO IA. METHODS: Eight ABO-IA-treated transplant candidates and 39 patients subjected to semiselective IA for a variety of different indications outside the context of ABO-incompatible transplantation were included. Antibody patterns (IgG, IgG1-4 subclasses, IgM, C4d-fixing reactivities) were analysed applying conventional agglutination testing and flow cytometry. RESULTS: As assessed by sensitive flow cytometric antibody detection, ABO-IA-based desensitization led to a profound even though often incomplete reduction of anti-A/B reactivities. Persistent complement- or non-complement-fixing reactivities, however, were not associated with transplant rejection or capillary C4d deposition. Single sessions of semiselective IA turned out to be more effective than ABO-IA in decreasing levels of anti-A/B IgG [median reduction to 28 versus 59% (ABO-IA) of baseline values, P < 0.001). In contrast, BG-specific IgM (74 versus 30%, P < 0.001) and IgG3 (72 versus 42%, P < 0.05) were reduced to a lesser extent, without differences between tested adsorber types. Analysis of four consecutive IA sessions revealed that inferior efficiency could not be overcome by serial treatment. CONCLUSION: Our observation of limited adsorption capacities regarding distinct BG-specific Ig (sub)classes suggests caution in applying semiselective IA techniques in ABO incompatible kidney transplantation. PMID- 22086973 TI - Albumin-binding capacity (ABiC) is reduced in patients with chronic kidney disease along with an accumulation of protein-bound uraemic toxins. AB - BACKGROUND: Albumin is an important transport protein for non-water-soluble protein-bound drugs and uraemic toxins. Its transport capacity is reduced in patients with advanced chronic kidney disease (CKD) and unbound fractions of uraemic toxins are related to complications of CKD. We investigated whether this reduction could be quantified and how it correlated with the stages of CKD. Albumin-binding capacity (ABiC) is a dye-based method that quantifies the remaining binding capacity of one major binding site (site II) of the albumin molecule. METHODS: Blood samples from 104 CKD patients were incubated with a binding site-specific fluorescent marker and the amount of unbound marker was determined by means of fluorescence detection after filtration. Measurements in a pooled human plasma were used for reference. Glomerular filtration rate and serum indoxyl sulphate (IS) levels were also determined. RESULTS: Impairment of renal function was associated with a reduction in ABiC (mean +/- SD: 118 +/- 12; 111 +/ 11; 99 +/- 8 and 79 +/- 9% for Stages 1/2, 3, 4 and 5, respectively; P < 0.001) and an increase in IS (3.9 +/- 1.1; 6.2 +/- 3.2; 16.3 +/- 14.9 and 56.1 +/- 28.6 MUmol/L for Stages 1/2, 3, 4 and 5, respectively; P < 0.001). In dialysis patients, ABiC was lower in those with urine outputs <500 mL/day than in those with preserved urine output (73.7 +/- 6.0 versus 83.8 +/- 8.5%; P < 0.001). CONCLUSION: Impaired albumin function in CKD patients can be quantified, is related to severity of kidney disease and is associated with an accumulation of uraemic albumin-bound retention solutes. PMID- 22086974 TI - Pathogenicity of A600V variant in exon 12 of the MSH2 gene detected in a Japanese kindred with Lynch syndrome. AB - Lynch syndrome is caused by germline mutations of the DNA mismatch repair genes. Missense mutations are often difficult to evaluate as pathogenic. Previously, we reported a missense mutation in exon 12 at codon 600 of the MSH2 gene, causing a substitution of GTT (Val) for GCT (Ala) in a 35-year-old-man with rectal cancer, while the pathogenicity of this mutation is still unclear. In this report, we confirm the same mutation in his 66-year-old mother who had cecal cancer. PCR/direct sequencing analysis of peripheral blood lymphocytes revealed the same missense mutation in exon 12 at codon 600 of the MSH2 gene. The wave height of the capillary sequencer from the wild-type allele was decreased in tumor tissue, indicating loss of heterozygosity in the wild-type allele. Analysis of the tumor showed microsatellite instability high and loss of MSH2 protein expression. This sequence variant has not been reported in another family. This mutation is considered to play a significant and causative role in Lynch syndrome. PMID- 22086975 TI - Bioactivation versus detoxication of the urothelial carcinogen aristolochic acid I by human cytochrome P450 1A1 and 1A2. AB - Exposure to aristolochic acid (AA) is associated with human nephropathy and urothelial cancer. Individual susceptibility to AA-induced disease likely reflects individual differences in enzymes that metabolize AA. Herein, we evaluated AAI metabolism by human cytochrome P450 (CYP) 1A1 and 1A2 in two CYP1A humanized mouse lines that carry functional human CYP1A1 and CYP1A2 genes in the absence of the mouse Cyp1a1/1a2 orthologs. Human and mouse hepatic microsomes and human CYPs were also studied. Human CYP1A1 and 1A2 were found to be principally responsible for reductive activation of AAI to form AAI-DNA adducts and for oxidative detoxication to 8-hydroxyaristolochic acid (AAIa), both in the intact mouse and in microsomes. Overall, AAI-DNA adduct levels were higher in CYP1A humanized mice relative to wild-type mice, indicating that expression of human CYP1A1 and 1A2 in mice leads to higher AAI bioactivation than in mice containing the mouse CYP1A1 and 1A2 orthologs. Furthermore, an exclusive role of human CYP1A1 and 1A2 in AAI oxidation to AAIa was observed in human liver microsomes under the aerobic (i.e., oxidative) conditions. Because CYP1A2 levels in human liver are at least 100-fold greater than those of CYP1A1 and there exists a > 60 fold genetic variation in CYP1A2 levels in human populations, the role of CYP1A2 in AAI metabolism is clinically relevant. The results suggest that, in addition to CYP1A1 and 1A2 expression levels, in vivo oxygen concentration in specific tissues might affect the balance between AAI nitroreduction and demethylation, which in turn would influence tissue-specific toxicity or carcinogenicity. PMID- 22086976 TI - Parallel biotransformation of tetrabromobisphenol A in Xenopus laevis and mammals: Xenopus as a model for endocrine perturbation studies. AB - The flame retardant tetrabromobisphenol A (TBBPA) is a high production flame retardant that interferes with thyroid hormone (TH) signaling. Despite its rapid metabolism in mammals, TBBPA is found in significant amounts in different tissues. Such findings highlight first a need to better understand the effects of TBBPA and its metabolites and second the need to develop models to address these questions experimentally. We used Xenopus laevis tadpoles to follow radiolabeled (14)C-TBBPA uptake and metabolism. Extensive and rapid uptake of radioactivity was observed, tadpoles metabolizing > 94% of (14)C-TBBPA within 8 h. Four metabolites were identified in water and tadpole extracts: TBBPA-glucuronide, TBBPA-glucuronide-sulfate, TBBPA-sulfate, and TBBPA-disulfate. These metabolites are identical to the TBBPA conjugates characterized in mammals, including humans. Most radioactivity (> 75%) was associated with sulfated conjugates. The antithyroid effects of TBBPA and the metabolites were compared using two in vivo measures: tadpole morphology and an in vivo tadpole TH reporter gene assay. Only TBBPA, and not the sulfated metabolites, disrupted thyroid signaling. Moreover, TBBPA treatment did not affect expression of phase II enzymes involved in TH metabolism, suggesting that the antithyroid effects of TBBPA are not due to indirect effects on TH metabolism. Finally, we show that only the parent TBBPA inhibits T3-induced transactivation in cells expressing human, zebrafish, or X. laevis TH receptor, TRalpha. We conclude, first, that perturbation of thyroid signaling by TBBPA is likely due to rapid direct action of the parent compound, and second, that Xenopus is an excellent vertebrate model for biotransformation studies, displaying homologous pathways to mammals. PMID- 22086977 TI - Homeostatic synaptic plasticity: local and global mechanisms for stabilizing neuronal function. AB - Neural circuits must maintain stable function in the face of many plastic challenges, including changes in synapse number and strength, during learning and development. Recent work has shown that these destabilizing influences are counterbalanced by homeostatic plasticity mechanisms that act to stabilize neuronal and circuit activity. One such mechanism is synaptic scaling, which allows neurons to detect changes in their own firing rates through a set of calcium-dependent sensors that then regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites. Additional homeostatic mechanisms may allow local changes in synaptic activation to generate local synaptic adaptations, and network-wide changes in activity to generate network-wide adjustments in the balance between excitation and inhibition. The signaling pathways underlying these various forms of homeostatic plasticity are currently under intense scrutiny, and although dozens of molecular pathways have now been implicated in homeostatic plasticity, a clear picture of how homeostatic feedback is structured at the molecular level has not yet emerged. On a functional level, neuronal networks likely use this complex set of regulatory mechanisms to achieve homeostasis over a wide range of temporal and spatial scales. PMID- 22086978 TI - Propentofylline decreases tumor growth in a rodent model of glioblastoma multiforme by a direct mechanism on microglia. AB - Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer, with a median survival of less than 2 years after diagnosis. The tumor microenvironment plays a critical role in tumor invasion and progression. Microglia and infiltrating macrophages are the most abundant immune cells in the tumor. In the present study, we demonstrate that systemic propentofylline (PPF), an atypical methylxanthine with central nervous system (CNS) glial modulating and anti-inflammatory actions, significantly decreased tumor growth in a CNS-1 rat model of GBM by targeting microglia and not tumor cells. Rats received tumor injections of 1 * 10(5) CNS-1 cells in the right striatum with daily intraperitonial injections of PPF (50 mg/kg) or saline beginning the day of tumor injection. PPF did not cause apoptosis or decrease proliferation of CNS-1 tumor cells. Furthermore, we demonstrate, using in vitro methods, that PPF decreased microglial migration toward CNS-1 tumor cells and decreased MMP-9 expression. The effects of PPF were shown to be specific to microglia and not peripheral macrophages. These results support a differential functional role of resident microglia and infiltrating macrophages in the brain tumor environment. Our data highlight microglia as a crucial target for future therapeutic development and present PPF as a possible drug for treatment of human GBM. PMID- 22086979 TI - Paraoxonase 1 as a major bioactivating hydrolase for olmesartan medoxomil in human blood circulation: molecular identification and contribution to plasma metabolism. AB - Olmesartan medoxomil (OM) is a prodrug-type angiotensin II type 1 receptor antagonist. The OM-hydrolyzing enzyme responsible for prodrug bioactivation was purified from human plasma through successive column chromatography and was molecularly identified through N-terminal amino acid sequencing, which resulted in a sequence of 20 amino acids identical to that of human paraoxonase 1 (PON1). Two recombinant allozymes of human PON1 (PON1(192QQ) and PON1(192RR)) were constructed and were clearly demonstrated to hydrolyze OM; hydrolysis by the latter allozyme was slightly faster than that by the former. In addition, we evaluated the contribution of PON1 to OM bioactivation in human plasma. Enzyme kinetic studies demonstrated that OM was hydrolyzed more effectively by the recombinant PON1 proteins than by purified albumin. The OM-hydrolyzing activities of the recombinant PON1 proteins and diluted plasma were greatly reduced in the absence of calcium ions. Immunoprecipitation with anti-PON1 IgG completely abolished the OM-hydrolyzing activity in human plasma, whereas the activity was partially inhibited with anti-albumin IgG. The distribution pattern of the OM hydrolyzing activity in human serum lipoprotein fractions and lipoprotein deficient serum was examined and showed that most of the OM-hydrolyzing activity was located in the high-density lipoprotein fraction, with which PON1 is closely associated. In conclusion, we identified PON1 as the OM-bioactivating hydrolase in human plasma on a molecular basis and demonstrated that PON1, but not albumin, plays a major role in OM bioactivation in human plasma. PMID- 22086980 TI - Increased systemic exposure to rhizoma coptidis alkaloids in lipopolysaccharide pretreated rats attributable to enhanced intestinal absorption. AB - Rhizoma coptidis is a rhizome commonly used in traditional Chinese medicine. After oral administration of rhizoma coptidis extract, the plasma concentrations of its effective alkaloid constituents are so low that their systemic therapeutic actions cannot be explained. This study aimed to investigate the influence of lipopolysaccharide (LPS) on the pharmacokinetics of the rhizoma coptidis alkaloids. Pharmacokinetic experiments were performed with rats; both in vitro absorption and efflux experiments were carried out with everted rat gut sacs, whereas in vitro metabolism experiments were conducted with rat liver microsomes and intestinal S9 fractions. Mucosal changes were evaluated with light microscopy and transmission electron microscopy. The results showed that, in rat plasma, LPS pretreatment increased systemic alkaloid exposure. LPS pretreatment increased the in vitro absorption of the alkaloids and decreased their efflux. The efflux of vinblastine and rhodamine 123, P-glycoprotein substrates, also was decreased. The absorption of fluorescein isothiocyanate-labeled dextran (average molecular mass, 4 kDa), a gut paracellular permeability probe, was not influenced. Obvious damage was observed in the mucosa, but the tight junctions between epithelial cells remained intact. Intestinal, rather than hepatic, alkaloid metabolism was decreased. These findings indicated that LPS pretreatment increased systemic exposure to the alkaloids through enhancement of their absorption, which was related to decreased intestinal efflux and metabolism. The results add to the understanding of why rhizoma coptidis is active despite the low plasma concentrations of the rhizoma coptidis alkaloids measured in normal subjects and experimental animals. PMID- 22086981 TI - The influence of health care reform on intensive care: a UK perspective. PMID- 22086982 TI - Reslizumab and eosinophilic asthma: one step closer to phenotype-directed therapy? PMID- 22086983 TI - Pneumonia in the ICU: a lethal or VAPid complication? PMID- 22086984 TI - Understanding ICU staff burnout: the show must go on. PMID- 22086985 TI - Chronic kidney disease: a new morbidity of cystic fibrosis or an old morbidity of diabetes mellitus? PMID- 22086986 TI - Where next for gene expression profiling? So much promise. PMID- 22086987 TI - VEGF receptor inhibition as a model of pulmonary hypertension in mice. PMID- 22086988 TI - Physiologic phenotypes of sleep apnea pathogenesis. PMID- 22086989 TI - An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. AB - BACKGROUND: Pulmonary embolism (PE) is a leading cause of maternal mortality in the developed world. Along with appropriate prophylaxis and therapy, prevention of death from PE in pregnancy requires a high index of clinical suspicion followed by a timely and accurate diagnostic approach. METHODS: To provide guidance on this important health issue, a multidisciplinary panel of major medical stakeholders was convened to develop evidence-based guidelines for evaluation of suspected pulmonary embolism in pregnancy using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. In formulation of the recommended diagnostic algorithm, the important outcomes were defined to be diagnostic accuracy and diagnostic yield; the panel placed a high value on minimizing cumulative radiation dose when determining the recommended sequence of tests. RESULTS: Overall, the quality of the underlying evidence for all recommendations was rated as very low or low, with some of the evidence considered for recommendations extrapolated from studies of the general population. Despite the low-quality evidence, strong recommendations were made for three specific scenarios: performance of chest radiography (CXR) as the first radiation-associated procedure; use of lung scintigraphy as the preferred test in the setting of a normal CXR; and performance of computed-tomographic pulmonary angiography (CTPA) rather than digital subtraction angiography (DSA) in a pregnant woman with a nondiagnostic ventilation-perfusion (V/Q) result. DISCUSSION: The recommendations presented in this guideline are based upon the currently available evidence; availability of new clinical research data and development and dissemination of new technologies will necessitate a revision and update. PMID- 22086990 TI - An uncommon complication of an inferior vena cava filter. PMID- 22086991 TI - Discriminatory value of procalcitonin. PMID- 22086992 TI - Trends in cause-specific mortality in oxygen-dependent COPD: what about pulmonary embolism? PMID- 22086993 TI - Is autoimmunity really related to the pathogenesis of COPD? PMID- 22086994 TI - Recording of possible diaphragm fatigue under neurally adjusted ventilatory assist. PMID- 22086995 TI - Efficacy of adalimumab in chronically active and symptomatic patients with sarcoidosis. PMID- 22086996 TI - Mobilizing the genome of Lepidoptera through novel sequence gains and end creation by non-autonomous Lep1 Helitrons. AB - Transposable elements (TEs) can affect the structure of genomes through their acquisition and transposition of novel DNA sequences. The 134-bp repetitive elements, Lep1, are conserved non-autonomous Helitrons in lepidopteran genomes that have characteristic 5'-CT and 3'-CTAY nucleotide termini, a 3'-terminal hairpin structure, a 5'- and 3'-subterminal inverted repeat (SIR), and integrations that occur between AT or TT nucleotides. Lep1 Helitrons have acquired and propagated sequences downstream of their 3'-CTAY termini that are 57 344-bp in length and have termini composed of a 3'-CTRR preceded by a 3'-hairpin structure and a region complementary to the 5'-SIR (3'-SIRb). Features of both the Lep1 Helitron and multiple acquired sequences indicate that secondary structures at the 3'-terminus may have a role in rolling circle replication or genome integration mechanisms, and are a prerequisite for novel end creation by Helitron-like TEs. The preferential integration of Lep1 Helitrons in proximity to gene-coding regions results in the creation of genetic novelty that is shown to impact gene structure and function through the introduction of novel exon sequence (exon shuffling). These findings are important in understanding the structural requirements of genomic DNA sequences that are acquired and transposed by Helitron-like TEs. PMID- 22086998 TI - Transcriptome sequencing of Hevea brasiliensis for development of microsatellite markers and construction of a genetic linkage map. AB - To obtain more information on the Hevea brasiliensis genome, we sequenced the transcriptome from the vegetative shoot apex yielding 2 311 497 reads. Clustering and assembly of the reads produced a total of 113 313 unique sequences, comprising 28 387 isotigs and 84 926 singletons. Also, 17 819 expressed sequence tag (EST)-simple sequence repeats (SSRs) were identified from the data set. To demonstrate the use of this EST resource for marker development, primers were designed for 430 of the EST-SSRs. Three hundred and twenty-three primer pairs were amplifiable in H. brasiliensis clones. Polymorphic information content values of selected 47 SSRs among 20 H. brasiliensis clones ranged from 0.13 to 0.71, with an average of 0.51. A dendrogram of genetic similarities between the 20 H. brasiliensis clones using these 47 EST-SSRs suggested two distinct groups that correlated well with clone pedigree. These novel EST-SSRs together with the published SSRs were used for the construction of an integrated parental linkage map of H. brasiliensis based on 81 lines of an F1 mapping population. The map consisted of 97 loci, consisting of 37 novel EST-SSRs and 60 published SSRs, distributed on 23 linkage groups and covered 842.9 cM with a mean interval of 11.9 cM and ~4 loci per linkage group. Although the numbers of linkage groups exceed the haploid number (18), but with several common markers between homologous linkage groups with the previous map indicated that the F1 map in this study is appropriate for further study in marker-assisted selection. PMID- 22086999 TI - Mycoplasma hyopneumoniae transcription unit organization: genome survey and prediction. AB - Mycoplasma hyopneumoniae is associated with swine respiratory diseases. Although gene organization and regulation are well known in many prokaryotic organisms, knowledge on mycoplasma is limited. This study performed a comparative analysis of three strains of M. hyopneumoniae (7448, J and 232), with a focus on genome organization and gene comparison for open read frame (ORF) cluster (OC) identification. An in silico analysis of gene organization demonstrated 117 OCs and 34 single ORFs in M. hyopneumoniae 7448 and J, while 116 OCs and 36 single ORFs were identified in M. hyopneumoniae 232. Genomic comparison revealed high synteny and conservation of gene order between the OCs defined for 7448 and J strains as well as for 7448 and 232 strains. Twenty-one OCs were chosen and experimentally confirmed by reverse transcription-PCR from M. hyopneumoniae 7448 genome, validating our prediction. A subset of the ORFs within an OC could be independently transcribed due to the presence of internal promoters. Our results suggest that transcription occurs in 'run-on' from an upstream promoter in M. hyopneumoniae, thus forming large ORF clusters (from 2 to 29 ORFs in the same orientation) and indicating a complex transcriptional organization. PMID- 22087000 TI - Discovery of deoxyceramides and diacylglycerols as CD1b scaffold lipids among diverse groove-blocking lipids of the human CD1 system. AB - Unlike the dominant role of one class II invariant chain peptide (CLIP) in blocking MHC class II, comparative lipidomics analysis shows that human cluster of differentiation (CD) proteins CD1a, CD1b, CD1c, and CD1d bind lipids corresponding to hundreds of diverse accurate mass retention time values. Although most ions were observed in association with several CD1 proteins, ligands binding selectively to one CD1 isoform allowed the study of how differing antigen-binding grooves influence lipid capture. Although the CD1b groove is distinguished by its unusually large volume (2,200 A(3)) and the T' tunnel, the average mass of compounds eluted from CD1b was similar to that of lipids from CD1 proteins with smaller grooves. Elution of small ligands from the large CD1b groove might be explained if two small lipids bind simultaneously in the groove. Crystal structures indicate that all CD1 proteins can capture one antigen with its hydrophilic head group exposed for T-cell recognition, but CD1b structures show scaffold lipids seated below the antigen. We found that ligands selectively associated with CD1b lacked the hydrophilic head group that is generally needed for antigen recognition but interferes with scaffold function. Furthermore, we identified the scaffolds as deoxyceramides and diacylglycerols and directly demonstrate a function in augmenting presentation of a small glycolipid antigen to T cells. Thus, unlike MHC class II, CD1 proteins capture highly diverse ligands in the secretory pathway. CD1b has a mechanism for presenting either two small or one large lipid, allowing presentation of antigens with an unusually broad range of chain lengths. PMID- 22087001 TI - Brassinosteroids modulate the efficiency of plant immune responses to microbe associated molecular patterns. AB - Metazoans and plants use pattern recognition receptors (PRRs) to sense conserved microbial-associated molecular patterns (MAMPs) in the extracellular environment. In plants, the bacterial MAMPs flagellin and elongation factor Tu (EF-Tu) activate distinct, phylogenetically related cell surface pattern recognition receptors of the leucine-rich repeat receptor kinase (LRR-RK) family called FLS2 and EF-Tu receptor, respectively. BAK1 is an LRR-RK coreceptor for both FLS2 and EF-Tu receptor. BAK1 is also a coreceptor for the plant brassinosteroid (BR) receptor, the LRR-RK BRI1. Binding of BR to BRI1 primarily promotes cell elongation. Here, we tune the BR pathway response to establish how plant cells can generate functionally different cellular outputs in response to MAMPs and pathogens. We demonstrate that BR can act antagonistically or synergistically with responses to MAMPs. We further show that the synergistic activities of BRs on MAMP responses require BAK1. Our results highlight the importance of plant steroid homeostasis as a critical step in the establishment of plant immunity. We propose that tradeoffs associated with plasticity in the face of infection are layered atop plant steroid developmental programs. PMID- 22086997 TI - Analysis of the Asian seabass transcriptome based on expressed sequence tags. AB - Analysis of transcriptomes is of great importance in genomic studies. Asian seabass is an important fish species. A number of genomic tools in it were developed, while large expressed sequence tag (EST) data are lacking. We sequenced ESTs from nine normalized cDNA libraries and obtained 11 431 high quality ESTs. We retrieved 8524 ESTs from dbEST database and analyzed all 19 975 ESTs using bioinformatics tools. After clustering, we obtained 8837 unique sequences (2838 contigs and 5999 singletons). The average contig length was 574 bp. Annotation of these unique sequences revealed that 48.9% of them showed significant homology to RNA sequences in GenBank. Functional classification of the unique ESTs identified a broad range of genes involved in different functions. We identified 6114 putative single-nucleotide polymorphisms and 634 microsatellites in ESTs. We discovered different temporal and spatial expression patterns of some immune-related genes in the Asian seabass after challenging with a pathogen Vibrio harveyi. The unique EST sequences are being used in developing a cDNA microarray to examine global gene expression and will also facilitate future whole-genome sequence assembly and annotation of Asian seabass and comparative genomics. PMID- 22087002 TI - Shared gene expression in distinct neurons expressing common selector genes. AB - Expression of the mec-3/unc-86 selector gene complex induces the differentiation of the touch receptor neurons (TRNs) of Caenorhabditis elegans. These genes are also expressed in another set of embryonically derived mechanosensory neurons, the FLP neurons, but these cells do not share obvious TRN traits or proteins. We have identified ~300 genes in each cell type that are up-regulated at least threefold using DNA microarrays. Twenty-three percent of these genes are up regulated in both cells. Surprisingly, some of the common genes had previously been identified as TRN-specific. Although the FLP neurons contain low amounts of the mRNAs for these TRN genes, they do not have detectable proteins. These results suggest that transcription control is relatively inexact but that these apparent errors of transcription are tolerated and do not alter cell fate. Previous studies showed that loss of the EGL-44 and EGL-46 transcription factors cause the FLP neurons to acquire TRN-like traits. Here, we show that similar changes occur (e.g., the expression of both the TRN mRNAs and proteins) when the FLP neurons ectopically express the auxiliary transcription factor ALR-1 (Aristaless related), which ensures, but does not direct, TRN differentiation. Thus, the FLP neurons can acquire a TRN-like fate but use multiple levels of regulation to ensure they do not. Our data indicate that expression of common master regulators in different cell types can result in inappropriate expression of effector genes. This misexpression makes these cells vulnerable to influences that could cause them to acquire alternative fates. PMID- 22087003 TI - Mycobacterium tuberculosis protein tyrosine phosphatase (PtpA) excludes host vacuolar-H+-ATPase to inhibit phagosome acidification. AB - Mycobacterium tuberculosis (Mtb) pathogenicity depends on its ability to inhibit phagosome acidification and maturation processes after engulfment by macrophages. Here, we show that the secreted Mtb protein tyrosine phosphatase (PtpA) binds to subunit H of the macrophage vacuolar-H(+)-ATPase (V-ATPase) machinery, a multisubunit protein complex in the phagosome membrane that drives luminal acidification. Furthermore, we show that the macrophage class C vacuolar protein sorting complex, a key regulator of endosomal membrane fusion, associates with V ATPase in phagosome maturation, suggesting a unique role for V-ATPase in coordinating phagosome-lysosome fusion. PtpA interaction with host V-ATPase is required for the previously reported dephosphorylation of VPS33B and subsequent exclusion of V-ATPase from the phagosome during Mtb infection. These findings show that inhibition of phagosome acidification in the mycobacterial phagosome is directly attributed to PtpA, a key protein needed for Mtb survival and pathogenicity within host macrophages. PMID- 22087004 TI - In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid-polymeric nanoparticles. AB - Following recent successes with percutaneous coronary intervention (PCI) for treating coronary artery disease (CAD), many challenges remain. In particular, mechanical injury from the procedure results in extensive endothelial denudation, exposing the underlying collagen IV-rich basal lamina, which promotes both intravascular thrombosis and smooth muscle proliferation. Previously, we reported the engineering of collagen IV-targeting nanoparticles (NPs) and demonstrated their preferential localization to sites of arterial injury. Here, we develop a systemically administered, targeted NP system to deliver an antiproliferative agent to injured vasculature. Approximately 60-nm lipid-polymeric NPs were surface functionalized with collagen IV-targeting peptides and loaded with paclitaxel. In safety studies, the targeted NPs showed no signs of toxicity and a >=3.5-fold improved maximum tolerated dose versus paclitaxel. In efficacy studies using a rat carotid injury model, paclitaxel (0.3 mg/kg or 1 mg/kg) was i.v. administered postprocedure on days 0 and 5. The targeted NP group resulted in lower neointima-to-media (N/M) scores at 2 wk versus control groups of saline, paclitaxel, or nontargeted NPs. Compared with sham-injury groups, an ~50% reduction in arterial stenosis was observed with targeted NP treatment. The combination of improved tolerability, sustained release, and vascular targeting could potentially provide a safe and efficacious option in the management of CAD. PMID- 22087005 TI - Reduced impact logging minimally alters tropical rainforest carbon and energy exchange. AB - We used eddy covariance and ecological measurements to investigate the effects of reduced impact logging (RIL) on an old-growth Amazonian forest. Logging caused small decreases in gross primary production, leaf production, and latent heat flux, which were roughly proportional to canopy loss, and increases in heterotrophic respiration, tree mortality, and wood production. The net effect of RIL was transient, and treatment effects were barely discernable after only 1 y. RIL appears to provide a strategy for managing tropical forest that minimizes the potential risks to climate associated with large changes in carbon and water exchange. PMID- 22087006 TI - Brassinosteroids inhibit pathogen-associated molecular pattern-triggered immune signaling independent of the receptor kinase BAK1. AB - Plants and animals use innate immunity as a first defense against pathogens, a costly yet necessary tradeoff between growth and immunity. In Arabidopsis, the regulatory leucine-rich repeat receptor-like kinase (LRR-RLK) BAK1 combines with the LRR-RLKs FLS2 and EFR in pathogen-associated molecular pattern (PAMP) triggered immunity (PTI) and the LRR-RLK BRI1 in brassinosteroid (BR)-mediated growth. Therefore, a potential tradeoff between these pathways mediated by BAK1 is often postulated. Here, we show a unidirectional inhibition of FLS2-mediated immune signaling by BR perception. Unexpectedly, this effect occurred downstream or independently of complex formation with BAK1 and associated downstream phosphorylation. Thus, BAK1 is not rate-limiting in these pathways. BRs also inhibited signaling triggered by the BAK1-independent recognition of the fungal PAMP chitin. Our results suggest a general mechanism operative in plants in which BR-mediated growth directly antagonizes innate immune signaling. PMID- 22087007 TI - Hypermorphic mutation of the voltage-gated sodium channel encoding gene Scn10a causes a dramatic stimulus-dependent neurobehavioral phenotype. AB - The voltage-gated sodium channel Na(v)1.8 is known to function in the transmission of pain signals induced by cold, heat, and mechanical stimuli. Sequence variants of human Na(v)1.8 have been linked to altered cardiac conduction. We identified an allele of Scn10a encoding the alpha-subunit of Na(v)1.8 among mice homozygous for N-ethyl-N-nitrosourea-induced mutations. The allele creates a dominant neurobehavioral phenotype termed Possum, characterized by transient whole-body tonic immobility induced by pinching the skin at the back of the neck ("scruffing"). The Possum mutation enhanced Na(v)1.8 sodium currents and neuronal excitability and heightened sensitivity of mutants to cold stimuli. Striking electroencephalographic changes were observed concomitant with the scruffing-induced behavioral change. In addition, electrocardiography demonstrated that Possum mice exhibited marked sinus bradycardia and R-R variability upon scruffing, abrogated by infusion of atropine. However, atropine failed to prevent or mitigate the tonic immobility response. Hyperactive sodium conduction via Na(v)1.8 thus leads to a complex neurobehavioral phenotype, which resembles catatonia in schizophrenic humans and tonic immobility in other mammals upon application of a discrete stimulus; no other form of mechanosensory stimulus could induce the immobility phenotype. Our data confirm the involvement of Na(v)1.8 in transducing pain initiated by cold and additionally implicate Na(v)1.8 in previously unknown functions in the central nervous system and heart. PMID- 22087008 TI - Observational studies find association between chocolate consumption and reduced risk of cardiovascular disease and diabetes. PMID- 22087009 TI - 2.64% of South Korean children aged 7 to 12 have autism spectrum disorders. PMID- 22087010 TI - Type III glycogen storage disease mimicking hypertrophic cardiomyopathy. PMID- 22087011 TI - Shape of the right ventricular outflow Doppler envelope and severity of pulmonary hypertension. AB - BACKGROUND: It is now well known that timing of right ventricular outflow tract (RVOT) spectral Doppler signals change with increasing pulmonary hypertension severity. We devised a study to determine whether visual assessment of these RVOT Doppler signals can be useful identifying the severity of pulmonary hypertension. METHODS: Visual inspection of pulsed RVOT Doppler signals from 120 consecutive patients (mean age of 55 +/- 12, range 29-89 years; 45 males); with a mean pulmonary artery systolic pressure (PASP) of 59 +/- 29, (ranging from 18 to 150 mmHg), of whom 78 patients had PASP >40 mmHg, was performed and correlated with standard echo Doppler variables of right ventricular performance. RESULTS: Visual inspection of RVOT spectral Doppler signals from the 120 patients showed four dynamic patterns and on a stepwise multiple regression analysis, PASP was the only echocardiographic variable that correlated with these different types of RVOT spectral Doppler signals. Furthermore, receiver operator curve analysis of these RVOT spectral Doppler signals correlated well with different ranges of PASP. CONCLUSIONS: Visual assessment of RVOT spectral signals demonstrates the presence of four dynamic patterns, independent of the aetiology of the pulmonary hypertension, that not only correlate with the severity of pulmonary hypertension, but also are useful in identifying a range of PASP with great accuracy that minimizes subjective interpretation. These simple visual assessments of RVOT Doppler signals can be done routinely when evaluating patients with pulmonary hypertension without the need of additional sophisticated equipment. PMID- 22087012 TI - Scleroderma renal crisis: a retrospective multicentre study on 91 patients and 427 controls. AB - OBJECTIVE: Scleroderma renal crisis (SRC) is a severe manifestation of SSc, whose prognosis remains severe, despite treatment with angiotensin-converting-enzyme inhibitor and dialysis. This study was undertaken to describe SRC characteristics, prognosis and outcome, and evaluate the responsibility of CSs in its occurrence. METHODS: Analysis concerned 91 SSc patients with SRC who were compared with 427 non-SRC-SSc patients taken as controls. RESULTS: Among the 91 SRC patients, 71 (78.0%) had high blood pressure, 53 (58.2%) hypertensive encephalopathy and 51 (56.0%) thrombotic microangiopathy; 64 (70.3%) had received CSs before or concomitantly with SRC vs 156 (36.5%) non-SRC-SSc patients (P < 0.001). Treated SRC patients also received more prednisone 29.3 (28.4) vs 3.6 (9.9) mg than controls (P < 0.001). SRC clinical outcomes were poor: 49 (53.8%) patients required dialysis, which was definitive for 38. Thirty-seven (40.7%) SRC patients died vs 10.8% of the controls (P < 0.001). Death was most frequent among dialysed patients who never recovered renal function (22 vs 2) and 13 never dialysed SRC patients died. CONCLUSIONS: Although SRC prognosis has improved markedly, SRC remains a severe manifestation of SSc, despite treatment with angiotensin-converting enzyme inhibitor and dialysis. CSs contributed significantly to SRC occurrence. PMID- 22087013 TI - Assessment of work instability in spondyloarthritis: a cross-sectional study using the ankylosing spondylitis work instability scale. AB - OBJECTIVES: Work status is an important outcome in SpA. The objective was to assess work instability and its determinants in a cohort of patients with SpA, using the AS-work instability scale (AS-WIS). METHODS: We performed a cross sectional monocentre study. Patients were definite SpA patients with paid work. Work instability was measured by the AS-WIS. Its determinants were assessed by correlations with SpA scores (BASDAI, BASFI and patient's global assessment) and patients with low work instability (AS-WIS score < 11) were compared with those with moderate to high instability, through backward logistic regression. RESULTS: In all, 156 patients were assessed: mean (s.d.) age 41 (11) years, mean disease duration 15 (11) years; 71 (45.5%) were on TNF blockers. The mean AS-WIS score was 9.5 (5.5); 55 (35%) patients had moderate and 8 (5%) patients had high work instability. Correlations of the AS-WIS score with SpA scores were significant but moderate (BASDAI R = 0.42, BASFI R = 0.41, patient's global assessment R = 0.53; P < 0.0001). In multivariate analysis, high patient's global assessment was the only element associated with moderate to high work instability; demographic characteristics and treatments were not significant elements. CONCLUSION: Work instability was found to be high and its main determinant was patient's global assessment. The predictive validity of the AS-WIS in terms of job retention should be further assessed. PMID- 22087015 TI - Economic studies in rheumatology: data, perspectives, challenges. PMID- 22087014 TI - Analysis of Class II human leucocyte antigens in Italian and Spanish systemic sclerosis. AB - OBJECTIVE: To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry. METHODS: Nine hundred and forty four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10 000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted. RESULTS: In both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR) = 2.069, 95% asymptotic CIs (CI(95)) 1.486, 2.881; P < 0.001] and in Spanish patients (OR = 6.707, CI(95) 3.974, 11.319; P < 0.001) as well as in anti-topo-positive patients: Italy (OR = 2.642, CI(95) 1.78, 3.924; P < 0.001) and Spain (OR = 20.625, CI(95) 11.536, 36.876; P < 0.001). In both the populations we also identified an additional risk allele (HLA DQB1*03) and a protective allele (HLA-DQB1*0501) in anti-topo-positive patients. The meta-analysis showed different statistically significant associations, the most interesting being the differential association between HLA-DRB1*01 alleles and ACAs (OR = 1.724, CI(95) 1.482, 2.005; P < 0.001) or topo I antibodies (OR = 0.5, CI(95) 0.384, 0.651; P < 0.001). CONCLUSIONS: We describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc. PMID- 22087016 TI - CD40 gene polymorphisms confer risk of Behcet's disease but not of Vogt-Koyanagi Harada syndrome in a Han Chinese population. AB - OBJECTIVES: Recent genetic surveys including a genome-wide association study have identified CD40 as a susceptibility gene for several autoimmune diseases. This study was designed to investigate the association of CD40 gene polymorphisms with Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population. METHODS: Two single nucleotide polymorphisms (SNPs), rs4810485 and rs1883832, were genotyped using polymerase chain reaction-restriction fragment length polymorphism in 373 BD patients, 519 VKH patients and 402 controls. A binary logistic regression analysis was applied to assess the influence of gender on the association of CD40 polymorphisms with BD. RESULTS: Our results showed significantly increased frequencies of the homozygous rs4810485 TT and rs1883832 TT in BD patients as compared with the controls [Bonferroni-corrected P-value for gender adjustment (Pac) = 0.006, odds ratio (OR) = 1.98, 95% confidence interval (CI) 1.38, 2.83; = 0.012, OR = 1.73, 95% CI 1.22, 2.46, respectively]. A markedly decreased frequency of the heterozygous rs4810485 GT was observed in BD patients as compared with the controls ( = 0.042, OR = 0.68, 95% CI 0.51, 0.90). The genotype and allele frequencies of rs4810485 and rs1883832 were not different between VKH patients and controls. Stratification analysis did not find any association between the tested SNPs and extra-ocular manifestations of both diseases. CONCLUSIONS: The results suggest that TT genotypes of rs4810485 and rs1883832 may be predisposing genotypes for BD, and that the rs4810485 GT genotype may be a protective genotype for BD. The two tested CD40 gene polymorphisms are not associated with VKH syndrome in the investigated Han Chinese population. PMID- 22087017 TI - Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats. AB - Studies from genetic modification and spontaneous mutations show that C-type natriuretic peptide (CNP) signalling plays an essential part in postnatal endochondral growth, but measurement of CNP proteins and changes in their abundance in tissues and plasma during normal growth has not been reported. Using rodent pups with GH deficiency, we now describe the pharmacodynamic response of CNP and rat amino-terminal proCNP (NTproCNP) in plasma and tissues, and relate these to changes in linear growth (nose-tail length, tibial length and tibial growth plate width) during the course of 1 week of GH or saline (control) administration. Compared with saline, significant increases in plasma and tissue CNP forms were observed after 24 h in GH-treated pups and before any detectable change in linear growth. Whereas CNP abundance was increased in most tissues (muscle, heart and liver) by GH, enrichment was the greatest in extracts from growth plates and kidney. Plasma and tissue concentrations in GH-treated pups were sustained or further increased at 1 week when strong positive associations were found between plasma NTproCNP and linear growth or tissue concentrations. High content of NTproCNP in kidney tissue strongly correlated with plasma concentrations, which is consistent with previous data showing renal extraction of the peptide. In showing a prompt and significant increase in CNP in tissues driving normal endochondral growth, these findings provide further rationale for CNP agonists in the treatment of growth disorders resistant to current therapies and support the use of CNP concentrations as biomarkers of linear growth. PMID- 22087019 TI - A comparison of algorithms for body-worn sensor-based spatiotemporal gait parameters to the GAITRite electronic walkway. AB - This study compares the performance of algorithms for body-worn sensors used with a spatiotemporal gait analysis platform to the GAITRite electronic walkway. The mean error in detection time (true error) for heel strike and toe-off was 33.9 +/ 10.4 ms and 3.8 +/- 28.7 ms, respectively. The ICC for temporal parameters step, stride, swing and stance time was found to be greater than 0.84, indicating good agreement. Similarly, for spatial gait parameters--stride length and velocity- the ICC was found to be greater than 0.88. Results show good to excellent concurrent validity in spatiotemporal gait parameters, at three different walking speeds (best agreement observed at normal walking speed). The reported algorithms for body-worn sensors are comparable to the GAITRite electronic walkway for measurement of spatiotemporal gait parameters in healthy subjects. PMID- 22087020 TI - Alcohol induced epigenetic perturbations during the inflammatory stage of fracture healing. AB - It is well recognized by orthopedic surgeons that fractures of alcoholics are more difficult to heal successfully and have a higher incidence of non-union, but the mechanism of alcohol's effect on fracture healing is unknown. In order to give direction for the study of the effects of alcohol on fracture healing, we propose to identify gene expression and microRNA changes during the early stages of fracture healing that might be attributable to alcohol consumption. As the inflammatory stage appears to be the most critical for successful fracture healing, this paper focuses on the events at day three following fracture or the stage of inflammation. Sprague-Dawley rats were placed on an ethanol-containing or pair-fed Lieber and DeCarli diet for four weeks prior to surgical fracture. Following insertion of a medullary pin, a closed mid-diaphyseal fracture was induced using a Bonnarens and Einhorn fracture device. At three days' post fracture, the region of the fracture calluses was harvested from the right hind limb. RNA was extracted and microarray analysis was conducted against the entire rat genome. There were 35 genes that demonstrated significant increased expression due to alcohol consumption and 20 that decreased due to alcohol. In addition, the expression of 20 microRNAs was increased and six decreased. In summary, while it is recognized that mRNA levels may or may not represent protein levels successfully produced by the cell, these studies reveal changes in gene expression that support the hypothesis that alcohol consumption affects events involved with inflammation. MicroRNAs are known to modulate mRNA and these findings were consistent with much of what was seen with mRNA microarray analysis, especially the involvement of smad4 which was demonstrated by mRNA microarray, microRNA and polymerase chain reaction. PMID- 22087021 TI - A new recombinant human apolipoprotein E mimetic peptide with high-density lipoprotein binding and function enhancing activity. AB - We generated a novel human apolipoprotein E (apoE)-mimetic peptide, designated EpK. EpK contains an N-terminal cysteine residue, a low-density lipoprotein receptor-binding fragment, a 6 * lysine linker and a lipid-binding fragment. The recombinant peptide was expressed in Escherichia coli, and purified with a chitin bead column followed by a Heparin Sepharose CL-6B column to yield pure peptide. EpK displayed high solubility in aqueous solution at neutral pH and adopted a low content of alpha-helical structure which was significantly increased in 2,2,2 trifluoroethanol or upon lipid binding. EpK retained similar 1,2-dimyristoyl(d54) sn-glycero-3-phosphocholine binding activity as human apoE3 albeit with slower kinetics. Cell culture studies showed that EpK mediated cholesterol efflux from cholesterol-loaded primary murine macrophages with higher mass-based efficiency than human apoAI and human apoE3, and that EpK inhibited lipopolysaccharide (LPS) induced proinflammatory cytokine expression in murine macrophages. When injected into apoE(-/-)mice, EpK predominantly associated with high-density lipoprotein (HDL), which was also shown in in vitro incubation experiments. Moreover, association of EpK with HDL enhanced the ability of HDL in mediating cholesterol efflux and suppressing LPS-induced proinflammatory cytokine expression in cholesterol-loaded human acute monocytic leukemia cell line (THP-1) macrophages. These data suggest that this novel recombinant apoE mimetic peptide enhances HDL function and harbors antiatherogenic potential. PMID- 22087022 TI - Chronic angiotensin receptor blockade suppresses intracardiac angiotensin II in angiotensin II-infused rats. AB - Accumulation of angiotensin II (Ang II) in tissues is an Ang II-receptor-mediated process. In pigs, acute angiotensin receptor blockade (ARB) reduced the heart-to plasma ratio of Ang II following acute infusion. However in rats, chronic ARB treatment increased heart Ang II levels, suggesting that a differential response to ARB treatment may exist in the mammalian heart. Furthermore, the changes in heart aldosterone following chronic ARB treatment are not well described. To address the discrepancy in heart Ang II concentrations following ARB treatment, three groups (n = 6) of rats were chronically studied: (1) control; (2) angiotensin II (Ang II; 80 ng/min for 28 d); and (3) angiotensin II + olmesartan (ARB; 10 mg/kg/d for 21 d). Ang II-infusion increased intracardiac Ang II by 40% (53 +/- 2 versus 74 +/- 6 fmol/g) and intrarenal Ang II over 2-fold (96 +/- 6 versus 207 +/- 14 fmol/g), and chronic ARB treatment decreased Ang II by 48% in the heart (50 +/- 7 fmol/g) and over two-fold in the kidney (92 +/- 7 fmol/g), suggesting that accumulation of Ang II in the heart is receptor-mediated as in the kidney. Ang II increased plasma aldosterone 2.5-fold (1.4 +/- 0.1 versus 3.5 +/- 1.2 nmol/L) and was exacerbated by ARB treatment (5.6 +/- 1.0 nmol/L). Intracardiac aldosterone was exacerbated by ARB treatment (control: 2.2 +/- 0.3; Ang II: 2.7 +/- 1.1; ARB: 7.8 +/- 1.7 pmol/g). Suppression of intracardiac Ang II with ARB is consistent with the existing view of Ang II-receptor-mediated uptake by tissues. PMID- 22087023 TI - Heme oxygenase-1 induction protects the heart and modulates cellular and extracellular remodelling after myocardial infarction in rats. AB - Heme oxygenase-1 (HO-1) is a cytoprotective enzyme, which regulates cell proliferation and has potential antifibrogenic properties. In the present study, we investigated the effects of pre-emptive HO-1 induction by cobalt protoporphyrin IX on the healing of myocardial infarction in rats. The proliferation and repair of cardiac cells was assessed by immunostaining of Ki67 and proliferating cell nuclear antigen, and apoptosis of cardiomyocytes by terminal deoxynucleotidyl transferase dUTP nick end labelling. Compared with control hearts, HO-1 induction reduced apoptosis and increased proliferation and repair of cardiomyocytes in the infarct border area during the first few days after infarction. Concomitantly, HO-1 decreased accumulation and proliferation of fibroblasts, and down-regulated procollagen type I expression in the infarct area. Furthermore, HO-1 increased expression of the anti-inflammatory cytokine, transforming growth factor-beta1, suggesting that the cardioprotective effect of HO-1 in the early phase of infarct healing may result partly from the suppression of the inflammatory response. In the remote myocardium, HO-1 inhibited both proliferation and apoptosis of cardiomyocytes, attenuated heart failure-induced increase in the repair of cardiomyocytes and decreased perivascular fibrosis, thereby potentially alleviating adverse ventricular remodelling. The cardioprotective effects of HO-1 in the late phase of infarct healing may be mediated partly by down-regulation of the profibrotic connective tissue growth factor (CTGF), as HO-1 decreased CTGF expression at week 4. In conclusion, our findings suggest an important role for HO-1 in maintaining cellular homeostasis in the postinfarction heart. Modulation of the HO-1 pathway may provide a new therapeutic approach to enhance the recovery of myocardial infarction and protect against pathological myocardial changes. PMID- 22087024 TI - Acute glucocorticoid administration rapidly suppresses basal and stress-induced hypothalamo-pituitary-adrenal axis activity. AB - Hypothalamo-pituitary-adrenal (HPA) axis activity is subject to negative feedback control by glucocorticoids. Although the rapid component of this feedback is widely considered to contribute to regulation of dynamic HPA activity, few in vivo data exist on the temporal and pharmacological characteristics of this phenomenon. Thus, frequent automated blood sampling was undertaken in rats to determine the effects of acute glucocorticoid administration on basal and stress induced corticosterone secretion. The glucocorticoid agonist methylprednisolone (5-2000 MUg) or dexamethasone (5-500 MUg) injected iv at the peak of the diurnal rhythm caused dose-dependent suppression of basal corticosterone secretion, which was attenuated by the glucocorticoid receptor antagonist RU38486. With 50 MUg methylprednisolone, the onset of this suppression occurred at 40 min and remained significant for 120 min. However, although higher doses led to a greater and more sustained suppression of endogenous corticosterone, the response was delayed by the emergence of an initial stimulatory response that imposed a finite minimum delay. A corticosterone response to injection of CRH (1 MUg, iv) during the period of maximal suppression indicated a suprapituitary site for the inhibitory effect glucocorticoid activation. This mechanism was supported by glucocorticoid injection immediately before a psychological stress (30 min, white noise); methylprednisolone caused dose-dependent attenuation of stress-induced corticosterone release and expression of the activity marker c-fos mRNA in the paraventricular nucleus but did not block the pituitary response to CRH. Thus, in rats, glucocorticoid receptor activation rapidly suppresses basal and stress induced HPA activity that operates, at least in part, through a central mechanism of action. PMID- 22087025 TI - Cannabinoid receptor type 1 (CB1) activation inhibits small GTPase RhoA activity and regulates motility of prostate carcinoma cells. AB - The cannabinoid receptor type 1 (CB1) is a G protein-coupled receptor that is activated in an autocrine fashion by the endocannabinoids (EC), N arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). The CB1 and its endogenous and synthetic agonists are emerging as therapeutic targets in several cancers due to their ability to suppress carcinoma cell invasion and migration. However, the mechanisms that the CB1 regulates cell motility are not well understood. In this study, we examined the molecular mechanisms that diminish cell migration upon the CB1 activation in prostate carcinoma cells. The CB1 activation with the agonist WIN55212 significantly diminishes the small GTPase RhoA activity but modestly increases the Rac1 and Cdc42 activity. The diminished RhoA activity is accompanied by the loss of actin/myosin microfilaments, cell spreading, and cell migration. Interestingly, the CB1 inactivation with the selective CB1 antagonist AM251 significantly increases RhoA activity, enhances microfilament formation and cell spreading, and promotes cell migration. This finding suggests that endogenously produced EC activate the CB1, resulting in chronic repression of RhoA activity and cell migration. Consistent with this possibility, RhoA activity is significantly diminished by the exogenous application of AEA but not by 2-AG in PC-3 cells (cells with very low AEA hydrolysis). Pretreatment of cells with a monoacylglycerol lipase inhibitor, JZL184, which blocks 2-AG hydrolysis, decreases the RhoA activity. These results indicate the unique CB1 signaling and support the model that EC, through their autocrine activation of CB1 and subsequent repression of RhoA activity, suppress migration in prostate carcinoma cells. PMID- 22087026 TI - Enhanced thecal androgen production is prenatally programmed in an ovine model of polycystic ovary syndrome. AB - One of the hallmarks of polycystic ovary syndrome (PCOS) is increased ovarian androgen secretion that contributes to the ovarian, hormonal, and metabolic features of this condition. Thecal cells from women with PCOS have an enhanced capacity for androgen synthesis. To investigate whether this propensity is a potential cause, rather than a consequence, of PCOS, we used an ovine prenatal androgenization model of PCOS and assessed ewes at 11 months of age. Pregnant Scottish Greyface ewes were administered 100 mg testosterone propionate (TP) or vehicle control twice weekly from d 62 to 102 of gestation, and female offspring (TP = 9, control = 5) were studied. Prenatal TP exposure did not alter ovarian morphology or cyclicity, or plasma androgen, estrogen, and gonadotropin concentrations, at this stage. However, follicle function was reprogrammed in vivo with increased proportions of estrogenic follicles (P < 0.05) in the TP exposed cohort. Furthermore, in vitro the thecal cells of follicles (>4 mm) secreted more LH-stimulated androstenedione after prenatal androgenization (P < 0.05), associated with increased basal expression of thecal StAR (P < 0.01), CYP11A (P < 0.05), HSD3B1 (P < 0.01), CYP17 (P < 0.05), and LHR (P < 0.05). This provides the first evidence of increased thecal androgenic capacity in the absence of a PCOS phenotype, suggesting a thecal defect induced during fetal life. PMID- 22087027 TI - The type 1 insulin-like growth factor receptor (IGF-IR) pathway is mandatory for the follistatin-induced skeletal muscle hypertrophy. AB - Myostatin inhibition by follistatin (FS) offers a new approach for muscle mass enhancement. The aim of the present study was to characterize the mediators responsible for the FS hypertrophic action on skeletal muscle in male mice. Because IGF-I and IGF-II, two crucial skeletal muscle growth factors, are induced by myostatin inhibition, we assessed their role in FS action. First, we tested whether type 1 IGF receptor (IGF-IR) is required for FS-induced hypertrophy. By using mice expressing a dominant-negative IGF-IR in skeletal muscle, we showed that IGF-IR inhibition blunted by 63% fiber hypertrophy caused by FS. Second, we showed that FS caused the same degree of fiber hypertrophy in wild-type and IGF II knockout mice. We then tested the role of the signaling molecules stimulated by IGF-IR, in particular the Akt/mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (S6K) pathway. We investigated whether Akt phosphorylation is required for the FS action. By cotransfecting a dominant negative form of Akt together with FS, we showed that Akt inhibition reduced by 65% fiber hypertrophy caused by FS. Second, we evaluated the role of mTOR in FS action. Fiber hypertrophy induced by FS was reduced by 36% in rapamycin-treated mice. Finally, because the activity of S6K is increased by FS, we tested its role in FS action. FS caused the same degree of fiber hypertrophy in wild-type and S6K1/2 knockout mice. In conclusion, the IGF-IR/Akt/mTOR pathway plays a critical role in FS-induced muscle hypertrophy. In contrast, induction of IGF-II expression and S6K activity by FS are not required for the hypertrophic action of FS. PMID- 22087028 TI - Deterioration of QT prolongation after successful catheter ablation for Wolff Parkinson-White syndrome. PMID- 22087029 TI - Appropriateness of the Zucker Diabetic Fatty rat as a model for diabetic microvascular late complications. AB - Male obese Zucker Diabetic Fatty (ZDF) rats develop type 2 diabetes around eight weeks of age, and are widely used as a model for human diabetes and its complications. The objective of the study was to test whether the complications manifested in the kidney and nerves of ZDF rats really correspond to human diabetic complications in their being related to the hyperglycaemic state. Four groups of ZDF rats were used. One lean (Fa/?) and one obese (fa/fa) untreated group served as non-diabetic and diabetic controls. In two further groups of obese (fa/fa) rats, diabetes was prevented by pioglitazone or delayed by food restriction. All rats were monitored up to 35 weeks of age with respect to their blood glucose, HbA1c and insulin levels, their kidney function (urinary glucose excretion, renal glucose filtration, glomerular filtration rate, albumin/creatinine ratio), and their nerve function (tactile and thermal sensory threshold and nerve conduction velocity). Pioglitazone prevented the development of diabetes, while food restriction delayed its onset for 8-10 weeks. Accordingly, kidney function parameters were similar to lean non-diabetic rats in pioglitazone-treated rats and significantly improved in food-restricted rats compared with obese controls. Kidney histology paralleled the functional results. By contrast, nerve functional evaluations did not mirror the differing blood glucose levels. We conclude that the ZDF rat is a good model for diabetic nephropathy, while alterations in nerve functions were not diabetes-related. PMID- 22087030 TI - Evaluation of two devices for point-of-care testing of haemoglobin in neonatal pigs. AB - In veterinary medicine, point-of-care testing (POCT) techniques have become popular, since they provide immediate results and only small amounts of blood are needed. However, their accuracy is controversial. Pigs are often used for research purposes and accurate measurement of haemoglobin (Hb) is important during invasive procedures. The aim of this study was to evaluate two different Hb POCT devices in neonatal pigs. A prospective study with 57 pigs of 3-6 weeks of age, weighing 4.1-6.2 kg (median 5.1 kg) was performed. Fifty-seven blood samples were analysed for Hb using a conductivity-based and a photometrical POCT device and compared with a photometrical reference method. Statistical analysis was performed with Bland-Altman analysis, Spearman correlation and Passing-Bablok regression analysis. Hb values ranged from 32 to 108 g/L (median 80 g/L) using the reference method. The bias of the photometrical method (HemoCue((r))) to the reference method was -1 g/L, with limits of agreement (LOA) of -7 to 6 g/L. The conductivity-based method (i-STAT((r))) had a bias of -15 g/L with LOA from -24 to -6 g/L. There was a significant association between protein values and the bias of i-STAT versus CellDyn (r(2) = 0.27, P < 0.05) but not with the bias of HemoCue versus CellDyn (r(2) = 0.001, P = 0.79). The lower the protein values were, the lower the Hb values were measured by the i-STAT. The conductivity-based measurement of Hb constantly underestimated Hb values, whereas the photometrical method demonstrated a better accuracy and is therefore more reliable for on-site measurement of Hb in pigs. PMID- 22087032 TI - Local application of neurotrophins specifies axons through inositol 1,4,5 trisphosphate, calcium, and Ca2+/calmodulin-dependent protein kinases. AB - Neurons are highly polarized cells that have structurally distinct processes-the axons and dendrites-that differentiate from common immature neurites. In cultured hippocampal neurons, one of these immature neurites stochastically initiates rapid extension and becomes an axon, whereas the others become dendrites. Various extracellular and intracellular signals contribute to axon specification; however, the specific intracellular pathways whereby particular extracellular stimuli lead to axon specification remain to be delineated. Here, we found that the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT 3) were required for axon specification in an autocrine or a paracrine fashion. Using local application with a micropipette to selectively stimulate individual neurites, we found that stimulation of a selected neurite by BDNF or NT-3 induced neurite outgrowth and subsequent axon formation. NT-3 induced a rapid increase in calcium ions (Ca(2+)) in an inositol 1,4,5-trisphosphate (IP(3))-dependent fashion as well as local activation of the Ca(2+) effector Ca(2+)/calmodulin dependent protein kinase kinase (CaMKK) in the growth cone. Inhibition of neurotrophin receptors or CaMKK attenuated NT-3-induced axon specification in cultured neurons and axon formation in cortical neurons in vivo. These results identify a role for IP(3)-Ca(2+)-CaMKK signaling in axon specification. PMID- 22087031 TI - Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21. AB - The mechanisms linking immune responses and inflammation with tumor development are not well understood. Here, we show that the soluble form of the extracellular matrix proteoglycan decorin controls inflammation and tumor growth through PDCD4 (programmed cell death 4) and miR-21 (microRNA-21) by two mechanisms. First, decorin acted as an endogenous ligand of Toll-like receptors 2 and 4 and stimulated production of proinflammatory molecules, including PDCD4, in macrophages. Second, decorin prevented translational repression of PDCD4 by decreasing the activity of transforming growth factor-beta1 and the abundance of oncogenic miR-21, a translational inhibitor of PDCD4. Moreover, increased PDCD4 abundance led to decreased release of the anti-inflammatory cytokine interleukin 10, thereby making the cytokine profile more proinflammatory. This pathway operates in both pathogen-mediated and sterile inflammation, as shown here for sepsis and growth retardation of established tumor xenografts, respectively. Decorin was an early response gene evoked by septic inflammation, and protein concentrations of decorin were increased in the plasma of septic patients and mice. In cancer, decorin reduced the abundance of anti-inflammatory molecules and increased that of proinflammatory molecules, thereby shifting the immune response to a proinflammatory state associated with reduced tumor growth. Thus, by stimulating proinflammatory PDCD4 and decreasing the abundance of miR-21, decorin signaling boosts inflammatory activity in sepsis and suppresses tumor growth. PMID- 22087033 TI - The long-term survival potential of mature T lymphocytes is programmed during development in the thymus. AB - The homeostatic maintenance of normal numbers of mature T lymphocytes in the immune system depends on signaling from the T cell antigen receptor (TCR) and the interleukin-7 receptor (IL-7R); however, it is unclear whether there is crosstalk between these two receptors. Here, we have identified a central role for TCR signaling during the development of T lymphocytes in the thymus in the determination of IL-7 function in mature T lymphocytes. We showed that Il7r expression in mature T cells was modulated by developmental TCR-dependent signals elicited during the process of positive selection in the thymus and that this mechanism was common to both CD4(+) and CD8(+) T cells. Control of Il7r expression by the TCR was limited to thymocytes because neither the abundance nor the function of IL-7Ralpha was affected by TCR signaling in peripheral T cells. Finally, we showed that thymocytes without optimal IL-7Ralpha abundance failed to form part of the pool of mature T lymphocytes that patrol the periphery of normal hosts, highlighting the importance of this mechanism in shaping the repertoire of lymphocytes that make up this population. PMID- 22087034 TI - Early detection of colorectal cancer: barriers to screening in the primary care setting. PMID- 22087035 TI - Awareness and knowledge of osteoporosis in Vietnamese women. AB - PURPOSE: Vietnamese women are at particular risk of osteoporosis and its complications. This study examined osteoporosis knowledge and awareness among Vietnamese women who have accessed health care. METHODS: A sample of 217 women, 13 to 76 years of age, who were attending 1 of 2 health care facilities in Da Nang, Vietnam, between November and December 2009 completed a questionnaire assessing their awareness of osteoporosis and measuring their knowledge using a 30-item instrument reflecting 9 knowledge domains (eg, risk factors, diagnosis, prognosis). RESULTS: A majority (81.6%) of the women had heard of osteoporosis. Awareness was associated with education, working in health care, and having a family member with osteoporosis. On average, Vietnamese women answered 49% of the knowledge questions correctly; scores ranged from 0 to 26 questions correct out of 30 (mean = 14.71 +/- 5.2, median = 15). Mean knowledge scores were higher among those reporting a family member with osteoporosis, nurses (vs other vocations), and women with a high school education or greater (relative to those who had not completed high school). More than 90% of the women expressed interest in a prevention and treatment program. CONCLUSIONS: Vietnamese women may have heard of osteoporosis, yet they would benefit from education targeting prevention and treatment of the disease. PMID- 22087036 TI - Abnormal weight status and associated characteristics of low-income Korean children. AB - BACKGROUND: This study reports the prevalence of abnormal weight and associated characteristics of low-income Korean children. Methods Health examination and survey were conducted nationally with 2033 low-income elementary students (mean age +/- SD = 9.42 +/- 1.65 years). Prevalence of abnormal weight and odds ratios (ORs) of health behaviors for abnormal weight groups were calculated. RESULTS: Prevalence was 8% for underweight and 16% for overweight/obese. Compared with normal weight children, overweight/obese children were more likely to eat a variety of foods (OR = 1.82, P = .04) and have 3 meals a day (OR = 2.07, P = .047), but they were more likely to be stressed by their appearance (OR = 3.88, P < .001). Underweight children were less likely to have night snacks (OR = 0.28, P = .038) and more stressed by academic performance (OR = 3.76, P = .005) but were less educated about physical education (OR = 3.19, P = .044) and substance abuse (OR = 2.78, P = .018). Conclusion Higher prevalence of abnormal weight among low income Korean children calls for attention to address both childhood obesity and underweight in public health research and practice. PMID- 22087037 TI - Adherence to antihypertensive treatment and its determinants among urban slum dwellers in Kolkata, India. AB - A cross-sectional study was conducted to determine the prevalence and predictors of adherence to modern antihypertensive pharmacotherapy among slum dwellers in Kolkata, India. Prevalence of adherence based on patient self-reports of consuming >=80% of the prescribed medications over a recall period of 1 week was found to be 73% (95% confidence interval = 68%-78%). Compared with their counterparts, the following patients were more likely to be adherent to treatment: patients hypertensive for >=5 years (2.98 times), those whose hypertension was detected during checkups for conditions related to hypertension (2.35 times), those living with <=4 family members (2.01 times), those with family income of >=3000 rupees (2.56 times), those who were getting free drugs (4.16 times), patients perceiving current blood pressure to be under control (2.23 times), and those satisfied with current treatment (3.77). Those adherent to their prescribed medications were 1.71 times more likely to achieve adequate control of hypertension compared with those who were not adherent. PMID- 22087038 TI - Changing landscape of malaria in China: progress and feasibility of malaria elimination. AB - Large-scale malaria control activities in China have been conducted with significant success, since the launch of the nationwide malaria control program. This study investigated the malaria distribution in China, particularly in provinces with high risks. Spatial and temporal data were assembled for all endemic or historically endemic areas and combined to identify common patterns and to investigate the actual changes in the burden of malaria in the country. Data were analyzed and the progress in malaria elimination feasibility was discussed. The results indicated that the current distribution of malaria and vectors associated could provide evidence on the assessment of the feasibility of the malaria elimination in China. PMID- 22087039 TI - Influence of spousal education on partner's self-rated health: cross-sectional study among 1382 married couples in Shanghai, China. AB - The effect of individual educational attainment on health has been extensively documented in western countries, whereas empirical evidence of education spillover effects in marital dyads is scarce and inconsistent. A total of 2764 individuals (or 1382 marital dyads) were surveyed in the Shanghai Healthy City Project 2008. Logistic regression models were used for analysis, and all analyses were stratified by gender. Significant protective associations were observed in univariate models linking general health status to the individual's own educational attainment and to their partner's educational level. After controlling for presence of chronic conditions, lifestyle factors, and social support, these associations were attenuated. The authors found a gender difference in the association of spouse's educational attainment with self-rated health. The influence of education on health may be partly mediated by lifestyle and other factors. PMID- 22087040 TI - Pandemic influenza and health system resource gaps in Bali: an analysis through a resource transmission dynamics model. AB - The failure to contain pandemic influenza A(H1N1) 2009 in Mexico has shifted global attention from containment to mitigation. Limited surveillance and reporting have, however, prevented detailed assessment of mitigation during the pandemic, particularly in low- and middle-income countries. To assess pandemic influenza case management capabilities in a resource-limited setting, the authors used a health system questionnaire and density-dependent, deterministic transmission model for Bali, Indonesia, determining resource gaps. The majority of health resources were focused in and around the provincial capital, Denpasar; however, gaps are found in every district for nursing staff, surgical masks, and N95 masks. A relatively low pathogenicity pandemic influenza virus would see an overall surplus for physicians, antivirals, and antimicrobials; however, a more pathogenic virus would lead to gaps in every resource except antimicrobials. Resources could be allocated more evenly across Bali. These, however, are in short supply universally and therefore redistribution would not fill resource gaps. PMID- 22087041 TI - Learning of idiomatic language expressions in a group intervention for children with autism. AB - In typical development, children learn an extensive range of idioms and other figurative (non-literal) language expressions during childhood and adolescence. However, many children with autism fall far behind in their idiom comprehension and production and never fully reach adult levels. The current study measured the effectiveness of a group idiom intervention for ten children, aged 7 to 12 years, with autism spectrum disorders. This intervention was conducted by a community based social skills program. The children were initially very low in idiom understanding, but were able to learn and remember the meaning of idiomatic phrases that they were taught during the 2-week-long intervention. The children showed greater increases at a delayed post-test for idioms trained in the intervention than idioms that were untrained controls. Implications for future educational possibilities are discussed. PMID- 22087042 TI - Verbal ability, social stress, and anxiety in children with autistic disorder. AB - The aims of this study were to evaluate the physiological stress and anxiety responses in children with autism following completion of a standardized, social evaluative stressor (Trier Social Stress Test-Child version), document the relationship between verbal ability, stress, and anxiety, and determine the association between stress and anxiety in children with autism and typical development. Results demonstrated the Trier Social Stress Test-Child version to be a benign stressor for children with autism. Lower verbal ability in children with autism did not predict salivary cortisol or anxiety responses. There was a lack of association between stress and anxiety for both groups, highlighting the importance of considering these terms as separate constructs. Clinical implications and the limited utility of the Trier Social Stress Test-Child version in evaluating psychosocial stress in autism are discussed. PMID- 22087043 TI - Friendship characteristics and activity patterns of adolescents with an autism spectrum disorder. AB - This study compared perceptions of adolescents' friendships between adolescents with an autism spectrum disorder (ASD) and their parents, examined factors associated with friendship qualities, and investigated the adolescents' reports on the activities they did with friends and how activity patterns differed by gender. Ninety-one adolescents with an ASD and their parents completed mail-based surveys during the summer months. Adolescents with an ASD identified more friends than did their parents, but they agreed on the friends' characteristics. About half of the adolescents spent an average of 4 hours per day with friends during the summer months. Male adolescents with an ASD most frequently played video games with friends, whereas females most frequently had conversations with friends. The findings suggest that adolescents with an ASD and their parents identify different peers as the adolescent's friends. The findings also reveal similarities and differences in friendships between adolescents with an ASD and typically developing adolescents. PMID- 22087044 TI - Pilot study of a school-based parent training program for preschoolers with ASD. AB - This study investigated the feasibility and preliminary effectiveness of a parenting training program designed for early intervention and early childhood special education (EI/ESCE) programs serving students with autistic spectrum disorders. Thirteen teachers representing three intermediate school districts implemented the intervention with 27 students and their parents. Eighty-nine percent of families completed the program. From pre- to post-intervention parents improved their use of the treatment strategies and children increased their rate of language during a parent-child interaction in their home. Parents and teachers reported significant gains in child mastery of social-communication skills and teachers, but not parents, reported a significant decrease in social impairment. Parents reported a significant decrease in parenting stress. Both groups rated the intervention highly in regard to treatment acceptability, perceived effectiveness, and usability. Findings suggest that this intervention can be feasibly implemented in public EI/ECSE settings, filling an important gap in services for intervention programs serving children with autistic spectrum disorders. PMID- 22087045 TI - A social competence intervention for young children with high functioning autism and Asperger syndrome: a pilot study. AB - The key features of Asperger Syndrome (AS) and high functioning autism (HFA) include marked and sustained impairment in social interactions. A multi-session, small group program was developed to increase social perception based on the assumption perceptual or interpretive problems underlying these social difficulties. Additionally, the group format espoused a play therapy orientation and the use of sociodramatic play was the primary therapeutic modality used. Qualitative analyses of the data resulted in an explanation of the key changes in social interactions that took place through the course of the intervention. Although each participant's experience in this group was unique, all children in this program demonstrated improvements in their social interactions, as they experienced development both emotionally and behaviorally. Findings suggest that, despite their rigid interests and behavior patterns, the social limitations of these children improved when provided with the necessary environmental resources. PMID- 22087046 TI - Lipid lowering in patients with chronic kidney disease: a SHARP turn in the wrong direction? AB - The question whether lipid-lowering treatment is associated with a decrease in cardiovascular morbidity and mortality in patients with chronic kidney disease has been disputed for a while, with recent trials in patients on haemodialysis failing to show benefit. Recently, the long-awaited results of the SHARP (Study of Heart And Renal Protection) trial were published. This randomized trial compared the effects of either simvastatin 20 mg plus ezetimibe 10 mg daily or placebo on the occurrence of a first major vascular event in 9720 patients with chronic kidney disease. There was a 17% relative risk reduction but no benefit on survival. We address our concerns regarding the conclusions drawn from this trial. The trial has a major design flaw by comparing the effects of two different lipid-lowering drugs with placebo. Although the SHARP trial showed that lipid lowering may be beneficial for patients with chronic kidney disease, the clinically as well as economically important question remains unanswered as to whether it was statin therapy and/or ezetimibe that mediated this effect. A great opportunity to investigate superiority, equipoise, or potential inferiority of ezetimibe compared to statins was missed. PMID- 22087047 TI - Taking charge after stroke: promoting self-directed rehabilitation to improve quality of life--a randomized controlled trial. AB - OBJECTIVE: Few community interventions following stroke enhance activity, participation or quality of life. We tested two novel community interventions designed to promote self-directed rehabilitation following stroke. DESIGN: This was a randomized, controlled parallel group 2*2 trial. SETTING: Community. PARTICIPANTS: Maori and Pacific New Zealanders, >15 years old, randomized within three months of a new stroke. INTERVENTIONS: A DVD of four inspirational stories by Maori and Pacific people with stroke and a 'Take Charge Session'--a single structured risk factor and activities of daily living assessment, designed to facilitate self-directed rehabilitation. MAIN MEASURES: Primary outcomes were Health-related Quality of Life (Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the Short Form 36 (SF-36)) 12 months from randomization. Secondary outcomes were Barthel Index, Frenchay Activities Index, Carer Strain Index and modified Rankin score. RESULTS: One hundred and seventy two people were randomized with 139 (80.8%) followed up at 12 months post randomization. The effect of the Take Charge Session on SF-36 PCS at 12 months was 6.0 (95% confidence interval (CI) 2.0 to 10.0) and of the DVD was 0.9 (95% CI -3.1 to 4.9). Participants allocated to the Take Charge Session were less likely to have a modified Rankin score of >2 (odds ratio (OR) 0.42, 95% CI 0.2 to 0.89) and their carers had lower (better) Carer Strain Index scores (-1.5, 95% CI -2.8 to -0.1). CONCLUSION: A simple, low-cost intervention in the community phase of stroke recovery aiming to promote self-directed rehabilitation improved outcomes. PMID- 22087048 TI - Raman spectroscopy and microscopy based on mechanical force detection. AB - The Raman effect is typically observed by irradiating a sample with an intense light source and detecting the minute amount of frequency shifted scattered light. We demonstrate that Raman molecular vibrational resonances can be detected directly through an entirely different mechanism-namely, a force measurement. We create a force interaction through optical parametric down conversion between stimulated, Raman excited, molecules on a surface and a cantilevered nanometer scale probe tip brought very close to it. Spectroscopy and microscopy on clusters of molecules have been performed. Single molecules within such clusters are clearly resolved in the Raman micrographs. The technique can be readily extended to perform pump probe experiments for measuring inter- and intramolecular couplings and conformational changes at the single molecule level. PMID- 22087049 TI - Electromechanical properties and anisotropy of single- and multi-domain 0.72Pb(Mg(1/3)Nb(2/3))O(3)-0.28PbTiO(3) single crystals. AB - Complete sets of elastic, piezoelectric, and dielectric constants of 0.72Pb(Mg(1/3)Nb(2/3))O(3)-0.28PbTiO(3) single crystal poled along [111](c) (single domain) as well as non-polar axes [001](c) and [011](c) (multidomain) have been measured under natural conditions. These data allowed us to evaluate accurately the extrinsic contributions to the superior piezoelectric properties. Very large extrinsic contributions to the unusual anisotropies in multidomain crystals are confirmed. We found that the instability of domain structures is the origin of the low mechanical quality factor Q for the multidomain relaxor-based ferroelectric single crystals. Our results can provide useful guidance in future design of domain engineered materials. PMID- 22087050 TI - Tuning open-circuit voltage in organic solar cells by magnesium modified Alq(3). AB - The low molecular weight tris-(8-hydroxyquinoline) aluminum (Alq(3)) has been incorporated with magnesium (Mg) that altered the nature of its opto-electronic characteristics. The lowering of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in Mg:Alq(3), compared to pure Alq(3), creates a stronger field (exceeding the exciton binding energy) at the donor-acceptor junction to dissociate the photo-generated exciton and also provides a low barrier for electron transport across the device. In an electron only device (described in the text), a current enhancement in excess of 10(3), with respect to pure Alq(3), could be observed at 10 V applied bias. Optimized Mg:Alq(3) layer, when introduced in the photovoltaic device, improves the power conversion efficiencies significantly to 0.15% compared to the pure Alq(3) device. The improvement in the photovoltaic performance has been attributed to the superior exciton dissociation and carrier transport. PMID- 22087051 TI - Domain size engineering in tetragonal Pb(In(1/2)Nb(1/2))O(3) Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) crystals. AB - The effect of domain size on the dielectric and piezoelectric properties of [111] oriented tetragonal Pb(In(1/2)Nb(1/2))O(3)-Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) crystals was investigated. The dielectric permittivity (E(33 ) (T)/E(0)) and piezoelectric coefficient (d(33)) were found to be on the order of 13 800 and 1630 pC/N, respectively, for samples with domain size of ~500 nm, a 3-fold increase to crystals with domain size of ~50 MUm. Rayleigh analysis revealed that the extrinsic contribution to the piezoelectric response increased from ~8% to 30% with decreasing domain size, due to the increased domain wall density and associated irreversible domain wall motion. The enhanced properties were thought to relate to the fine domain structures, however, showing a poor electric field and temperature stabilities with domain size of 500 nm. Of particular significance is that samples with domain size being on the order of 5 MUm exhibit field and temperature stabilities, with yet high piezoelectric properties, make it potential for transducer applications. PMID- 22087052 TI - Hypomagnesemia and cardiovascular system. AB - Magnesium depletion in clinical practice is mainly related to loop diuretics and thiazides. Among patients treated with diuretics more than 1/3 exhibit hypomagnesa. Arrhythmias and sudden death attributed to magnesium depletion could be prevented by Mg administration. Magnesium deficiency in experimental animals promotes atherosclerotic lesions whereas this ion is involved in various stages of myocardial damage after experimental coronary artery occlusion. In humans magnesium administration in the first 24 hours of myocardial infarction was related to beneficial effects in first year mortality rate. Nevertheless more evidence from clinical investigation is needed for permanent conclutions. PMID- 22087054 TI - Quality of life survey and palliative care in lung cancer patients. AB - Aim. In patients with advanced and/or inoperable bronchial tumors, methods of palliative care such as radiotherapy, chemotherapy, brachytherapy and cryotherapy, singly and/or in combination, aiming at extending the survival time and improving the quality of life, were examined. Methods. One hundred and sixty three (163) patients, with mean age 67.9 yrs (range 22-25) and a male/female ratio at 1.34/1, treated between 2000-2004 were studied. Eighty one (81) patients receiving only cryotherapy presented a two-year survival rate at 19.3%, whilst eighty three (83) patients treated with radiotherapy or brachytherapy and/or chemotherapy showed a two-year survival rate at 25%. Sixty-five percent (65%) of patients only cryotreated had improvement in at least one or more Karnofsky and WHO indices. Results. Eighty percent (80%) of patients who received cryotherapy accompanied with supplementary palliative treatment showed amelioration of their clinical status. Conclusion. It seems that for patients with advanced or inoperable lung tumors, cryotherapy associated with additional palliative care may influence the survival time and improve their quality of life. PMID- 22087053 TI - Breast reconstruction with autologous tissue following mastectomy. AB - Breast cancer remains to be one of the most malignant diseases in the female population. It affects an essential part of female self-consciousness, and therefore causes a wide range of psychological traumas. The incidence in Europe and North America varies between 70 up to 100 new cases in 100.000 inhabitants per year. According to contemporary literature, mastectomy remains one of the most effective methods in the laborious effort to treat and overcome cancer. In this report the history of breast reconstruction is presented. The established methods which are taken into consideration after mastectomy and their clinical outcome are portrayed. The authors propose the free TRAM and DIEP flap as the methods of first choice after mastectomy, which offer most reliable transfer and low morbidity. In the recent past, increasing interest is observed for the SIEA flap. The free S-GAP flap is proposed for patients who are not candidates for a TRAM, DIEP or SIEA flap. Moreover, the pedicled Latissimus Dorsi flap remains still as a reliable, versatile alternative, particularly in case of contraindications for the above mentioned free flaps or when complications occurred. PMID- 22087055 TI - Endonasal bilateral simultaneous orbital decompression. AB - OBJECTIVE: To study the morbidity of the operation, to investigate it's safety and effectiveness in order to establish if it is reasonable to offer it as treatment to patients in one sitting instead of a staged procedure. Finally, to indentify the patient's long term satisfaction and to establish best practice. DESIGN: Retrospective case series study and prospective telephone interview. SETTING: Teaching General Hospital, Scotland, UK. SUBJECTS: 14 patients with dysthyroid orbitopathy who underwent the operation over a 4 year period. RESULTS: Proptosis improved in all but one of the cases. There was a relatively small morbidity and short inpatient stay. A significant amount of patients reported satisfaction with the results. All patients expressed strong preference for the simultaneous procedure instead of a staged one. CONCLUSIONS: The study shows that for the management of orbitopathy , bilateral simultaneous orbital decompression with endoscopic approach is a safe and effective operation, with small morbidity and significant patient satisfaction. Therefore, it is reasonable to offer it to patients instead of a staged procedure. PMID- 22087056 TI - Anterior cervical discectomy and interbody fusion with a dentate titanium cage: An experimental radiological and histopathological study in pigs. AB - Background - Aim: The distraction and stabilization provided by anterior cervical discectomy and fusion contribute to neural decompression and optimize osteogenesis. A new titanium cervical implant with specific properties was applied through an anterior approach in ten pigs. Implant behavior regarding in situ position and related osteogenesis were evaluated. METHODS: In this controlled animal study, the progress of fusion and osteogenesis was evaluated after one level cervical interbody fusion with a new titanium cage. Ten pigs underwent anterior cervical discectomy and fusion. No substitutes stimulating osteoblastic activity were used. Plain radiographs were carried out. The animals were euthanised 12 and 14 weeks after the operation respectively. Tissue samples were processed routinely and studied histologically. RESULTS: All pigs survived the surgery. Plain radiographs confirmed implant position. Histological analysis demonstrated fibrous connective tissue formation inside and around the implant which was largely transformed into cartilaginous and osseous tissue. CONCLUSIONS: Intervertebral space stabilization remains a parameter of crucial importance for early bone healing after anterior cervical discectomy and fusion. The new titanium alloy cage tested in this experimental study can offer the necessary stabilization for osteogenesis and adequate cervical interbody fusion without the need of growth factors. PMID- 22087057 TI - Cardiac rehabilitation effects on quality of life in patients after acute myocardial infarction. AB - Aim of this study was to investigate the significance of cardiac rehabilitation (CR) on Health Related Quality of Life ( HRQoL) in post acute myocardial infarction (AMI) patients. Methods. A total number off 110 individuals divided in 3 groups was included in the study. Group A consisted of 60 post-AMI pts participating in a CR program. It was a multidisciplinary rehabilitative approach including supervised bike exercise, with parallel education, counselling, psychological and social support, performed 3 times per week for 2 months after AMI . Group B consisted of 40 post-AMI pts not participating in any CR program while the control group C consisted of 10 apparently healthy people. HRQoL was evaluated by the Velasco-Del Barrio questionnaire. Questions on this questionnaire are reffered to 9 categories (health, sleep and rest, emotional behavior, concerns for the future, mobility, social interaction, alertness behavior, communication, work and leisure time). A 5-point scale (1=all of the time, 5=none of the time) and a special (1 to 8) coefficient for each parameter were used for the evaluation of each parameter. The highest score of 220 indicates the poorest QL. Results. Group A pts had better score of HRQoL as compared to Group B (94+/-3 vs 114+/-3, p<0.001) and slightly worse than Group C pts (94+/-4 vs 69+/-3, p<0.01).Significant difference was found among Group A and B pts regarding the most important evaluated parameters such as symptoms (17+/ 6.8 vs 22+/-6.5, p<0.001) and social behavior (21+/-4.2 vs 23+/-5.5, p<0.0001).Conclusion. It is concluded that participation in a multidisciplinary CR program significantly improves HRQoL in post AMI pts. All these pts must urged to take part in such programs. PMID- 22087058 TI - Experience from the use of absorbable type I collagen as haemostatic agent in obstetric and gynecological operations. AB - During the third stage of labour there are a lot of causes of significant hemorrhage. The commonest causes of acute hemorrhage are the uterine atony, the retained placenta, the lower tract lacerations, uterine rupture, placenta accreta, hereditary coagulopathy. Also, there could be significant bleeding, during caesarian section, usually at the time of removal of the placenta in cases of low lying placenta or placenta previa. A lot of times we have to confront serious hemorrhages in gynecological procedures like hysterectomies in cases of cervical, uterine or ovarian cancers. In order to deal with these problems successfully, general and specific measures are being taken. In cases of atonic uterus when all the other methods are unsuccessful we have to proceed to ligation of the internal iliac artery or even hysterectomy. MATERIAL-METHODS: We have tried to use the hemostatic type I collagen in obstetrical and gynecological cases in order to control the bleeding. We have used the collagen type I totally in 8 cases. Five of them were cases of atonic uterus after normal delivery or caesarian section and three of them were gynecological cases of uterine fibroids and ovarian cancer. RESULTS: By placing the collagen type I over the bleeding surfaces we have realized that in a very short period of time, there has been satisfactory control of the bleeding and immediate clinical improvement of the patient. In four out of five obstetrical cases that we have used the type I collagen, we have managed to avoid the hysterectomy. PMID- 22087059 TI - Pulmonary renal syndrome in an adult patient with Henoch-Shonlein purpura. AB - Henoch-Schonlein purpura (HSP) is a small vessel vasculitis characterized by purpuric skin rash, haematuria, abdominal pain, gastrointestinal bleeding and arthritis. Nephritis is more frequent and severe in adults than in children, with relatively more adults developing renal insufficiency. Another, fortunately rare, manifestation of HSP that increases mortality significantly, is diffuse alveolar haemorrhage. We report a rare case of an adult male patient with full-blown HSP that followed a respiratory tract infection. He successively, but not concurrently, developed all the clinical manifestations of HSP, i.e. arthritis, abdominal pain and bloody stools, a non-thrombocytopenic purpuric rash, and renal involvement; nephrotic range proteinuria first and haemodialysis-requiring nephritic syndrome later. Most interesting he developed life-threatening pulmonary haemorrhage fulfilling the criteria of the pulmonary-renal syndrome. An immunosuppressive regimen consisting of intravenous cyclophosphamide and corticosteroids was administered with success. In conclusion, HSP should be considered in the diagnosis of pulmonary-renal syndrome. In our opinion, the severity of the condition justifies the use of aggressive immunosuppressive treatment, like the one applied successfully to our patient. PMID- 22087060 TI - Repercussion of Mitochondria Deformity Induced by Anti-Hsp90 Drug 17AAG in Human Tumor Cells. AB - Inhibiting Hsp90 chaperone roles using 17AAG induces cytostasis or apoptosis in tumor cells through destabilization of several mutated cancer promoting proteins. Although mitochondria are central in deciding the fate of cells, 17AAG induced effects on tumor cell mitochondria were largely unknown. Here, we show that Hsp90 inhibition with 17AAG first affects mitochondrial integrity in different human tumor cells, neuroblastoma, cervical cancer and glial cells. Using human neuroblastoma tumor cells, we found the early effects associated with a change in mitochondrial membrane potential, elongation and engorgement of mitochondria because of an increased matrix vacuolization. These effects are specific to Hsp90 inhibition as other chemotherapeutic drugs did not induce similar mitochondrial deformity. Further, the effects are independent of oxidative damage and cytoarchitecture destabilization since cytoskeletal disruptors and mitochondrial metabolic inhibitors also do not induce similar deformity induced by 17AAG. The 1D PAGE LC MS/MS mitochondrial proteome analysis of 17AAG treated human neuroblastoma cells showed a loss of 61% proteins from membrane, metabolic, chaperone and ribonucleoprotein families. About 31 unmapped protein IDs were identified from proteolytic processing map using Swiss-Prot accession number, and converted to the matching gene name searching the ExPASy proteomics server. Our studies display that Hsp90 inhibition effects at first embark on mitochondria of tumor cells and compromise mitochondrial integrity. PMID- 22087061 TI - Investigation of the antibacterial activity of pioglitazone. AB - PURPOSE: To evaluate the antibacterial potential of pioglitazone, a member of the thiazolidinediones class of drugs, against Gram-positive (Streptococcus pneumoniae) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria. METHODS: Susceptibility testing was done using the antibiotic disk diffusion method and the minimal inhibitory concentration (MIC) of pioglitazone was measured according to the broth micro incubation standard method. RESULTS: Pioglitazone induced a dose-dependent antibacterial activity in which the optimal concentration was 80 MUM. Furthermore, results indicated that while E. coli was sensitive (MIC = 31.25 +/- 3.87 mg/L) to pioglitazone-induced cytotoxicity, S. pneumoniae and K. pneumoniae were resistant (MIC = 62.5 +/- 3.77 mg/L and MIC = 62.5 +/- 4.14 mg/L, respectively). Moreover, pretreatment of bacteria with a suboptimal concentration of pioglitazone (40 MUM) before adding amoxicillin, cephalexin, co-trimoxazole, or ciprofloxacin enhanced the antibacterial activity of all agents except co-trimoxazole. This enhancing effect was particularly seen against K. pneumoniae. CONCLUSION: These results indicate the possibility of a new and potentially important pioglitazone effect and the authors' ongoing studies aim to illustrate the mechanism(s) by which this antibacterial effect is induced. PMID- 22087062 TI - Bioequivalence assessment of two formulations of ibuprofen. AB - BACKGROUND: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz((r)), produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen((r)), manufactured by Boots Company, Nottingham, UK. METHODS AND RESULTS: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. CONCLUSION: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. PMID- 22087063 TI - Future prospects in the treatment of erectile dysfunction: focus on avanafil. AB - The treatment of erectile dysfunction (ED) has been revolutionized in the last 15 years with the introduction of type 5 phosphodiesterase (PDE5) inhibitors. Their efficacy, safety, and ease of administration have made them first-line treatment for ED. This article reviews the current therapies available for ED, and the new PDE5 inhibitors that are being investigated. Furthermore, it examines all the current ED treatment options that are in different phases of development (including oral and topical pharmacotherapy, gene therapy, and tissue engineering). A special emphasis is on avanafil, a new PDE5 inhibitor that has been studied extensively in Phase I and II clinical trials and has undergone several Phase III trials. Avanafil is a promising medication for ED due to its favorable pharmacokinetics, safety, and efficacy. PMID- 22087064 TI - Clinical utility of clodronate in the prevention and management of osteoporosis in patients intolerant of oral bisphosphonates. AB - Bisphosphonates have a long history in the treatment of osteoporosis and bone related disease. This review focuses on the use of a specific nonaminobisphosphonate, clodronate, which appears to be much better tolerated than other bisphosphonates and free of high-risk contraindications. Specifically, this paper reviews its use in the prevention of osteoporosis in postmenopausal women, taking into account its tolerability profile and recent safety issues arising regarding the use of bisphosphonates. PMID- 22087065 TI - Effectiveness of coordination exercise in improving cognitive function in older adults: a prospective study. AB - BACKGROUND: Studies on the effect of a low intensity coordination exercise on the elderly with limited mobility are sparse. This prospective study attempted to compare the effectiveness of a customized coordination exercise and a strength exercise in improving the cognitive functioning and physical mobility on the elderly. METHODS: Participants from two centers for the elderly were allocated to practice either an 8-week coordination training (CT) program or an 8-week towel exercise (TE) program. The Chinese Mini-Mental State Examination and Chinese Dementia Rating Scale (CDRS) were used to measure cognitive functioning of participants, and Timed Up-and-Go test for physical mobility. These assessments were administered before and after the program. RESULTS: Paired t-tests showed that the CDRS scores of the CT group improved significantly from 114.8 at pre test to 119.3 after training (P = 0.045). The CDRS scores of the TE group also improved from 114.9 at pre-test to 116.9 after training. CONCLUSION: Findings from this prospective study demonstrated that low-intensity level mind-body exercise could be beneficial to the cognitive functioning of older adults. PMID- 22087066 TI - Cognitive effects of calligraphy therapy for older people: a randomized controlled trial in Hong Kong. AB - BACKGROUND: This pilot study investigated the effects of calligraphy therapy on cognitive function in older Hong Kong Chinese people with mild cognitive impairment. METHODS: A single-blind, randomized controlled trial was carried out in a sample of 31 adults aged 65 years or older with mild cognitive impairment. They were randomly assigned to receive either intensive calligraphy training led by a trained research assistant for eight weeks (calligraphy group, n = 14) or no calligraphy treatment (control group, n = 17). Participants' cognitive function was assessed by the Chinese version of the Mini-Mental State Examination (CMMSE) before and after calligraphy treatment. Repeated measures analysis of variance and paired samples t-tests were used to analyze the data. RESULTS: A significant interaction effect of time and intervention was detected [F (1, 29) = 9.11, P = 0.005, eta(2) = 0.24]. The calligraphy group was found to have a prominent increase in CMMSE global score, and scores in the cognitive areas of orientation, attention, and calculation after two months (DeltaM = 2.36, P < 0.01), whereas their counterparts in the control group experienced a decline in CMMSE score (DeltaM = -0.41, P < 0.05). CONCLUSION: Calligraphy therapy was effective for enhancing cognitive function in older people with mild cognitive impairment and should be incorporated as part of routine programs in both community and residential care settings. PMID- 22087067 TI - Social facilitation in virtual reality-enhanced exercise: competitiveness moderates exercise effort of older adults. AB - This study examined the effect of virtual social facilitation and competitiveness on exercise effort in exergaming older adults. Fourteen exergaming older adults participated. Competitiveness was assessed prior to the start of exercise. Participants were trained to ride a "cybercycle;" a virtual reality-enhanced stationary bike with interactive competition. After establishing a cybercycling baseline, competitive avatars were introduced. Pedaling effort (watts) was assessed. Repeated measures ANOVA revealed a significant group (high vs low competitiveness) * time (pre- to post-avatar) interaction (F[1,12] = 13.1, P = 0.003). Virtual social facilitation increased exercise effort among more competitive exercisers. Exercise programs that match competitiveness may maximize exercise effort. PMID- 22087068 TI - Serum glucose level of healthy adolescents within Bukuru metropolis, Jos South Local Government Area, Plateau State, Nigeria. AB - PURPOSE: This study was designed to determine the blood glucose level of healthy adolescents living in the southern region of Plateau State in northern Nigeria. DESIGN: The study screened apparently healthy adolescents to identify individuals at high risk of developing diabetes mellitus. METHODS AND MATERIALS: Individuals who were confirmed healthy and not on any form of medication were enrolled in the study after the administration of a questionnaire which ruled out any form of aliment such as fever, gastroenteritis, and malaria. The serum glucose level was quantified using the glucose oxidase reagent. Data generated were analyzed using Excel 2007 (Microsoft((r)), Redmond, WA) and Student's t-test for an established normal range. RESULTS: The age distribution showed that those aged 14-16 years had a mean serum glucose level of 4.8 +/- 1.11 mmol/L, while in those aged 17-19 years it was 4.9 +/- 1.115 mmol/L, with a standard error of the mean of 0.17 and 0.15, respectively. The mean glucose level, weight, and height of the enrollees were 4.8 +/- 1.12 mmol/L, 56.6 +/- 6.20 kg, and 1.6 +/- 0.009 m, respectively. The mean serum glucose of those from the Berom tribe and other tribes was 4.9 +/- 1.21 mmol/L and 4.8 +/- 1.15 mmol/L, respectively. Analysis of the mean glucose level with respect to sex, age, tribe, weight, and height of the established normal mean resulted in a P value of <0.05, which was not significant. CONCLUSION: There was no significant difference in the serum glucose level of enrolled subjects. It was also observed that there was no significant difference between the glucose level based on the different tribes, sex, weight, and height of all enrolled subjects. Since glucose is involved with various body metabolic processes and is also an analyte of interest in diabetes mellitus, screening of adolescents would reduce the incidence of the disease. PMID- 22087069 TI - Patient's self-evaluation of two education programs for age-related skin changes in the face: a prospective, randomized, controlled study. AB - BACKGROUND: An interactive software program (HOYS) has been developed utilizing a database of digital images depicting various aspects and degrees of aging of exposed skin across seven geographic regions, representing a total of 35 facial and extrafacial subregions. A five-point photonumeric rating scale, which portrays age-related skin changes across five decades for each of these subregions, underpins this patient-based interactive self-assessment program. Based on the resulting outputs from this program, an individualized treatment prioritization list is generated for each region where significant differences between the patient's chronological and esthetic ages exist. This provides guidance for the patient and the treating physician on treatment options. METHODS: To evaluate the utility of HOYS in the clinic, relative to education programs currently used in Australian private esthetic clinics, a total of 95 esthetically-orientated patients were enrolled in a prospective, randomized, controlled, multicenter study. RESULTS: Compared with a prospective cohort of patients completing a standard education program commonly utilized in Australian esthetic clinics, patients receiving the HOYS education program reported greater empowerment through improved knowledge of specific age-related skin changes. This was associated with a clearer understanding of treatment options available to them, and a perceived ability to participate in the selection of the treatments potentially administered to improve their appearance. These differences between the two education groups were highly significant. CONCLUSION: Patients completing the HOYS patient education program have an improved understanding of age-related changes to exposed skin of their face, neck, decolletage, and hands. Due to the patient-specific nature of the program, these patients perceive a greater role in the deciding which esthetic treatments should be subsequently administered to enhance their appearance, through an improved understanding of the rationale for these treatments and indeed how they should be prioritized to achieve the best outcome for them. PMID- 22087070 TI - Susceptibility of Propionibacterium acnes isolated from patients with acne vulgaris to zinc ascorbate and antibiotics. AB - PURPOSE: The in vitro antimicrobial activity of ascorbic acid derivatives against Propionibacterium acnes was tested either alone or in combination with a variety of antimicrobial agents, and their fractional inhibitory concentration index was determined using checkerboard tests. The antimicrobial effectiveness of zinc ascorbate in the treatment of acne vulgaris, either alone or in combination with antibiotics such as clindamycin that are commonly used in Japan for the treatment of acne vulgaris, was therefore examined. MATERIALS AND METHODS: The antimicrobial susceptibility of 41 strains of clindamycin-sensitive and/or clindamycin-resistant P. acnes isolated from acne vulgaris patients was tested, in comparison with a type strain of P. acnes. RESULTS: Zinc ascorbate showed antimicrobial activity against a type strain of P. acnes and its concentration (0.064%) was sufficiently lower than the normal dose (5%) of other ascorbic acid derivatives. Combinations of zinc ascorbate with clindamycin, erythromycin, and chloramphenicol showed an additive effect, and zinc ascorbate alone effectively inhibited the growth of all P. acnes including clindamycin-resistant strains. CONCLUSION: The results provide novel evidence that the combination of zinc ascorbate and clindamycin is effective for acne vulgaris treatment. PMID- 22087071 TI - Amino ester hydrolase from Xanthomonas campestris pv. campestris, ATCC 33913 for enzymatic synthesis of ampicillin. AB - alpha-Amino ester hydrolases (AEH) are a small class of proteins, which are highly specific for hydrolysis or synthesis of alpha-amino containing amides and esters including beta-lactam antibiotics such as ampicillin, amoxicillin, and cephalexin. A BLAST search revealed the sequence of a putative glutaryl 7 aminocephalosporanic acid (GL-7-ACA) acylase 93% identical to a known AEH from Xanthomonas citri. The gene, termed gaa, was cloned from the genomic DNA of Xanthomonas campestris pv. campestris sp. strain ATCC 33913 and the corresponding protein was expressed into Escherichia coli. The purified protein was able to perform both hydrolysis and synthesis of a variety of alpha-amino beta-lactam antibiotics including (R)-ampicillin and cephalexin, with optimal ampicillin hydrolytic activity at 25 degrees C and pH 6.8, with kinetic parameters of k(cat) of 72.5 s(-1) and K(M) of 1.1 mM. The synthesis parameters alpha, beta(o), and gamma for ampicillin, determined here first for this class of proteins, are alpha = 0.25, beta(o) = 42.8 M(-1), and gamma = 0.23, and demonstrate the excellent synthetic potential of these enzymes. An extensive study of site directed mutations around the binding pocket of X. campestris pv. campestris AEH strongly suggests that mutation of almost any first-shell amino acid residues around the active site leads to inactive enzyme, including Y82, Y175, D207, D208, W209, Y222, and E309, in addition to those residues forming the catalytic triad, S174, H340, and D307. PMID- 22087072 TI - Precious essences: female secretions promote sperm storage in Drosophila. AB - Sperm that females receive during mating are stored in special places in the females' reproductive tracts. These storage sites serve to support and retain the sperm, maintaining the sperms' motility and, in mammals, permitting final sperm maturation. The molecules that attract sperm to these sites and mediate what happens to them there have remained elusive. New research, using elegant genetic tools in Drosophila, shows that secretory cells associated with a sperm storage organ are important in sperm-supportive functions. When females lack function of these cells, they do not store sperm, or the sperm that they do store lose motility. Intriguingly, these effects influence gametes beyond the secretory cells' immediate vicinity. Loss of these cells eliminates the motility of sperm stored elsewhere in the reproductive tract and prevents the movement of eggs through the tract to exit the female. As a result of the latter problem, fertilized eggs hatch inside female flies that lack these secretory cells: instead of laying eggs, these females can "give birth" to live offspring. Because the cellular source of these gamete-regulating substances is now known, future studies can identify the specific molecules and mechanisms by which a female attracts sperm into storage and regulates the movement of sperm and eggs within her reproductive tract. It will be fascinating to determine how these molecules and mechanisms maintain gametes in active and viable forms and how evolution can modulate this to result in diverse reproductive strategies. Identification of these molecules also has potential practical implications for strategies to regulate the reproduction of insects of medical or agricultural importance. PMID- 22087073 TI - Sperm-storage defects and live birth in Drosophila females lacking spermathecal secretory cells. AB - Male Drosophila flies secrete seminal-fluid proteins that mediate proper sperm storage and fertilization, and that induce changes in female behavior. Females also produce reproductive-tract secretions, yet their contributions to postmating physiology are poorly understood. Large secretory cells line the female's spermathecae, a pair of sperm-storage organs. We identified the regulatory regions controlling transcription of two genes exclusively expressed in these spermathecal secretory cells (SSC): Spermathecal endopeptidase 1 (Send1), which is expressed in both unmated and mated females, and Spermathecal endopeptidase 2 (Send2), which is induced by mating. We used these regulatory sequences to perform precise genetic ablations of the SSC at distinct time points relative to mating. We show that the SSC are required for recruiting sperm to the spermathecae, but not for retaining sperm there. The SSC also act at a distance in the reproductive tract, in that their ablation: (1) reduces sperm motility in the female's other sperm-storage organ, the seminal receptacle; and (2) causes ovoviviparity--the retention and internal development of fertilized eggs. These results establish the reproductive functions of the SSC, shed light on the evolution of live birth, and open new avenues for studying and manipulating female fertility in insects. PMID- 22087074 TI - Evolutionarily conserved linkage between enzyme fold, flexibility, and catalysis. AB - Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 A away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme-substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme-substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design. PMID- 22087075 TI - Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission. AB - Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease. PMID- 22087076 TI - Managing the demand for global health education. PMID- 22087078 TI - Rapid diagnosis of tuberculosis with the Xpert MTB/RIF assay in high burden countries: a cost-effectiveness analysis. AB - BACKGROUND: Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings. METHODS AND FINDINGS: We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%-85% to 95%-99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28-US$49 to US$133-US$146 and US$137-US$151 per TB case detected when Xpert is used "in addition to" and "as a replacement of" smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert "in addition to" smear microscopy, compared to the base case, range from US$41-$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert "as a replacement of" smear microscopy range from US$52 $138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold. CONCLUSIONS: Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings. PMID- 22087079 TI - Post-neonatal mortality, morbidity, and developmental outcome after ultrasound dated preterm birth in rural Malawi: a community-based cohort study. AB - BACKGROUND: Preterm birth is considered to be associated with an estimated 27% of neonatal deaths, the majority in resource-poor countries where rates of prematurity are high. There is no information on medium term outcomes after accurately determined preterm birth in such settings. METHODS AND FINDINGS: This community-based stratified cohort study conducted between May-December 2006 in Southern Malawi followed up 840 post-neonatal infants born to mothers who had received antenatal antibiotic prophylaxis/placebo in an attempt to reduce rates of preterm birth (APPLe trial ISRCTN84023116). Gestational age at delivery was based on ultrasound measurement of fetal bi-parietal diameter in early-mid pregnancy. 247 infants born before 37 wk gestation and 593 term infants were assessed at 12, 18, or 24 months. We assessed survival (death), morbidity (reported by carer, admissions, out-patient attendance), growth (weight and height), and development (Ten Question Questionnaire [TQQ] and Malawi Developmental Assessment Tool [MDAT]). Preterm infants were at significantly greater risk of death (hazard ratio 1.79, 95% CI 1.09-2.95). Surviving preterm infants were more likely to be underweight (weight-for-age z score; p<0.001) or wasted (weight-for-length z score; p<0.01) with no effect of gestational age at delivery. Preterm infants more often screened positively for disability on the Ten Question Questionnaire (p = 0.002). They also had higher rates of developmental delay on the MDAT at 18 months (p = 0.009), with gestational age at delivery (p = 0.01) increasing this likelihood. Morbidity-visits to a health centre (93%) and admissions to hospital (22%)-was similar for both groups. CONCLUSIONS: During the first 2 years of life, infants who are born preterm in resource poor countries, continue to be at a disadvantage in terms of mortality, growth, and development. In addition to interventions in the immediate neonatal period, a refocus on early childhood is needed to improve outcomes for infants born preterm in low-income settings. PMID- 22087077 TI - A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial. AB - BACKGROUND: Artemisinin-based combination therapies (ACTs) are the mainstay for the management of uncomplicated malaria cases. However, up-to-date data able to assist sub-Saharan African countries formulating appropriate antimalarial drug policies are scarce. METHODS AND FINDINGS: Between 9 July 2007 and 19 June 2009, a randomized, non-inferiority (10% difference threshold in efficacy at day 28) clinical trial was carried out at 12 sites in seven sub-Saharan African countries. Each site compared three of four ACTs, namely amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL), or chlorproguanil-dapsone-artesunate (CD+A). Overall, 4,116 children 6-59 mo old with uncomplicated Plasmodium falciparum malaria were treated (1,226 with AL, 1,002 with ASAQ, 413 with CD+A, and 1,475 with DHAPQ), actively followed up until day 28, and then passively followed up for the next 6 mo. At day 28, for the PCR adjusted efficacy, non-inferiority was established for three pair-wise comparisons: DHAPQ (97.3%) versus AL (95.5%) (odds ratio [OR]: 0.59, 95% CI: 0.37 0.94); DHAPQ (97.6%) versus ASAQ (96.8%) (OR: 0.74, 95% CI: 0.41-1.34), and ASAQ (97.1%) versus AL (94.4%) (OR: 0.50, 95% CI: 0.28-0.92). For the PCR-unadjusted efficacy, AL was significantly less efficacious than DHAPQ (72.7% versus 89.5%) (OR: 0.27, 95% CI: 0.21-0.34) and ASAQ (66.2% versus 80.4%) (OR: 0.40, 95% CI: 0.30-0.53), while DHAPQ (92.2%) had higher efficacy than ASAQ (80.8%) but non inferiority could not be excluded (OR: 0.35, 95% CI: 0.26-0.48). CD+A was significantly less efficacious than the other three treatments. Day 63 results were similar to those observed at day 28. CONCLUSIONS: This large head-to-head comparison of most currently available ACTs in sub-Saharan Africa showed that AL, ASAQ, and DHAPQ had excellent efficacy, up to day 63 post-treatment. The risk of recurrent infections was significantly lower for DHAPQ, followed by ASAQ and then AL, supporting the recent recommendation of considering DHAPQ as a valid option for the treatment of uncomplicated P. falciparum malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00393679; Pan African Clinical Trials Registry PACTR2009010000911750 PMID- 22087081 TI - Gastric juvenile polyposis with high-grade dysplasia in pachydermoperiostosis. AB - Pachydermoperiostosis (PDP) is the primary form of hypertrophic osteoarthropathy. It is a very rare disease consisting of pachydermia, digital clubbing and radiologic periostosis. Various digestive symptoms in PDP are seen in 11-49% of patients and juvenile polyps may be found at gastric endoscopy. We report here the history of a patient with PDP who was referred for assessment of severe anemia. Endoscopy of the upper digestive tract showed multiple polyps of the stomach with two huge lesions exhibiting foci of high-grade dysplasia. This observation suggests that PDP can be considered as a precancerous condition of the stomach and systematic screening using endoscopy should be considered in these patients. PMID- 22087082 TI - Appendiceal mucocele in an elderly patient: how much surgery? AB - Appendiceal mucoceles are rare cystic lesions with an incidence of 0.3-0.7% of all appendectomies. They are divided into four subgroups according to their histology. Even though the symptoms may vary - depending on the level of complication - from right lower quadrant pain, signs of intussusception, gastrointestinal bleeding to an acute abdomen with sepsis, most mucoceles are asymptomatic and found incidentally. We present the case of a 70-year-old patient with an incidentally found appendiceal mucocele. He was seen at the hospital for backache. The CT scan showed a vertebral fracture and a 7-cm appendiceal mass. A preoperative colonoscopy displayed several synchronous adenomas in the transverse and left colon with high-grade dysplasia. In order to lower the cancer risk of this patient, we performed a subtotal colectomy. The appendiceal mass showed no histopathological evidence of malignancy and no sign of perforation. The follow up was therefore limited to 2 months. In this case, appendectomy would have been sufficient to treat the mucocele alone. The synchronous high-grade dysplastic adenomas were detected in the preoperative colonoscopy and determined the therapeutic approach. Generally, in the presence of positive lymph nodes, a right colectomy is the treatment of choice. In the histological presence of mucinous peritoneal carcinomatosis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is indicated. In conclusion, mucoceles of the appendix are detected with high sensitivity by CT scan. If there is no evidence of synchronous tumor preoperatively and no peritoneal spillage, invasion or positive sentinel lymph nodes during surgery, a mucocele is adequately treated by appendectomy. PMID- 22087083 TI - Constipation-predominant irritable bowel syndrome associated to hyperprolactinemia. AB - Irritable bowel syndrome (IBS) is considered to be a physical disorder that mainly affects the bowel and is clinically characterized by lower abdominal pain or discomfort, diarrhea, constipation (or alternating diarrhea/constipation), gas, bloating, and nausea. According to recent studies, it appears that there is an association with increased prolactin levels in patients suffering from IBS. We report a rare case of regression of IBS symptoms (constipation type) in a 16-year old female adolescent after receiving cabergoline for treating hyperprolactinemia due to pituitary macroadenoma. Our hypothesis is that increased prolactin levels, for instance due to a pituitary adenoma, may suppress prolactin-releasing peptide release and lead to a reverse feedback interaction, consequently resulting in oversecretion of cholecystokinin, inducing the development of IBS. PMID- 22087084 TI - Autoimmune pancreatitis exhibiting multiple mass lesions. AB - Our case is a first report of autoimmune pancreatitis with multiple masses within the pancreas which was pathologically diagnosed by endoscopic ultrasound-guided fine needle aspiration and treated by steroid. The masses disappeared by steroid therapy. Our case is informative to know that autoimmune pancreatitis sometimes exhibits multiple masses within the pancreas and to diagnose it without unnecessary surgery. PMID- 22087085 TI - Usefulness of microcatheters inserted overnight for additional injection of sclerosant after initial balloon-occluded retrograde transvenous obliteration of gastric varices. AB - In patients with large gastric varices, dose limitation of the sclerosant can cause difficulties in achieving complete thrombosis of varices during a single balloon-occluded retrograde transvenous obliteration (BRTO) procedure. For patients with incomplete variceal thrombosis after the first BRTO, additional sclerosant must be injected in a second BRTO. We report a successful case of BRTO for large gastric varices in whom additional sclerosant was injected through a microcatheter that remained inserted overnight. To achieve complete variceal thrombosis in a patient with incomplete thrombosis of large gastric varices after a first BRTO, a retained microcatheter can be used to inject additional sclerosant in a second BRTO the next day. PMID- 22087086 TI - Intestinal Tuberculosis with Hoarseness as a Chief Complaint due to Mediastinal Lymphadenitis. AB - A 68-year-old woman was admitted to our hospital complaining of hoarseness. A chest X-ray detected an abnormal shadow on the upper right lung. Bronchoscopic examination revealed that the left vocal cord was fixed in the paramedian position, and therefore left recurrent nerve paralysis was suspected. Lymphadenopathy was found in the left supraclavicular area. Chest computed tomography showed that the pretracheal and subaortic lymph nodes were swollen. Gastroendoscopy showed a 2-cm protruding lesion with ulceration on the upper esophagus. Histological examination of the supraclavicular lymph nodes and biopsy specimens from the esophagus revealed non-specific inflammation. PET-CT showed abnormal accumulations not only on the upper right lung but also on the lower right of the abdomen. Colonoscopy was performed and multiple erosions on the terminal ileum were found. Polymerase chain reaction analysis of a specimen biopsied from the erosion of the terminal ileum was positive for Mycobacterium tuberculosis and intestinal tuberculosis was diagnosed. The patient was then treated with anti-tuberculous therapy. After treatment, the erosions on the terminal ileum, the swelling of the mediastinal lymphadenopathy, and the esophageal ulcer were all improved. The hoarseness was subsequently relieved. This is the first report of intestinal tuberculosis with hoarseness as a chief complaint due to mediastinal lymphadenitis. PMID- 22087087 TI - Fistula between the Jejunum and the Inferior Vena Cava after Esophagojejunal Anastomosis. AB - Fistulas between the luminal gastrointestinal tract and vascular structures can result from a variety of etiologies. While there have been reports of fistulas between the inferior vena cava and the duodenum, we report the first case to our knowledge of a fistula between the jejunum and the inferior vena cava after esophagojejunal anastomosis for recurrent esophageal adenocarcinoma. PMID- 22087088 TI - Social Comparison Affects Brain Responses to Fairness in Asset Division: An ERP Study with the Ultimatum Game. AB - Previous studies have shown that social comparison influences individual's fairness consideration and other-regarding behavior. However, it is not clear how social comparison affects the brain activity in evaluating fairness during asset distribution. In this study, participants, acting as recipients in the ultimatum game, were informed not only of offers to themselves but also of the average amount of offers in other allocator-recipient dyads. Behavioral results showed that the participants were more likely to reject division schemes when they were offered less than the other recipients, especially when the offers were highly unequal. Event-related brain potentials recorded from the participants showed that highly unequal offers elicited more negative-going medial frontal negativity than moderately unequal offers in an early time window (270-360 ms) and this effect was not significantly modulated by social comparison. In a later time window (450-650 ms), however, the late positive potential (LPP) was more positive for moderately unequal offers than for highly unequal offers when the other recipients were offered less than the participants, whereas this distinction disappeared when the other recipients were offered the same as or more than the participants. These findings suggest that the brain activity in evaluating fairness in asset division entails both an earlier (semi-) automatic process in which the brain responds to fairness at an abstract level and a later appraisal process in which factors related to social comparison and fairness norms come into play. PMID- 22087090 TI - The neural basis of implicit perceptual sequence learning. AB - The present fMRI study investigated the neural areas involved in implicit perceptual sequence learning. To obtain more insight in the functional contributions of the brain areas, we tracked both the behavioral and neural time course of the learning process, using a perceptual serial color matching task. Next, to investigate whether the neural time course was specific for perceptual information, imaging results were compared to the results of implicit motor sequence learning, previously investigated using an identical serial color matching task (Gheysen et al., 2010). Results indicated that implicit sequences can be acquired by at least two neural systems: the caudate nucleus and the hippocampus, having different operating principles. The caudate nucleus contributed to the implicit sequence learning process for perceptual as well as motor information in a similar and gradual way. The hippocampus, on the other hand, was engaged in a much faster learning process which was more pronounced for the motor compared to the perceptual task. Interestingly, the perceptual and motor learning process occurred on a comparable implicit level, suggesting that consciousness is not the main determinant factor dissociating the hippocampal from the caudate learning system. This study is not only the first to successfully and unambiguously compare brain activation between perceptual and motor levels of implicit sequence learning, it also provides new insights into the specific hippocampal and caudate learning function. PMID- 22087091 TI - Spiking signatures of spontaneous activity bursts in hippocampal cultures. AB - Dense dissociated hippocampal cultures are known to generate spontaneous bursting electrical activity which can be recorded by multielectrode arrays. We have analyzed spatio-temporal profiles of the distribution of spikes in the bursts recorded after 2 weeks in vitro. We have found a statistically significant similarity between the spiking patterns in sequential bursting events, we refer to these spiking patterns as spiking signatures. Such spiking signatures may appear in different parts of the bursts, including the activation patterns - the first spike times in the bursts, and deactivation patterns - the last spike times in the bursts. Moreover, these patterns may display apparent time scaling, e.g., they may be replayed in the subsequent bursts at different speeds, while preserving the spiking order. We discuss how such properties of the bursts may be associated with the formation of repeatable signaling pathways in cultured networks in vitro. PMID- 22087089 TI - Functional development of fronto-striato-parietal networks associated with time perception. AB - Compared to our understanding of the functional maturation of executive functions, little is known about the neurofunctional development of perceptive functions. Time perception develops during late adolescence, underpinning many functions including motor and verbal processing, as well as late maturing higher order cognitive skills such as forward planning and future-related decision making. Nothing, however, is known about the neurofunctional changes associated with time perception from childhood to adulthood. Using functional magnetic resonance imaging we explored the effects of age on the brain activation and functional connectivity of 32 male participants from 10 to 53 years of age during a time discrimination task that required the discrimination of temporal intervals of seconds differing by several hundred milliseconds. Increasing development was associated with progressive activation increases within left lateralized dorsolateral and inferior fronto-parieto-striato-thalamic brain regions. Furthermore, despite comparable task performance, adults showed increased functional connectivity between inferior/dorsolateral interhemispheric fronto frontal activation as well as between inferior fronto-parietal regions compared with adolescents. Activation in caudate, specifically, was associated with both increasing age and better temporal discrimination. Progressive decreases in activation with age were observed in ventromedial prefrontal cortex, limbic regions, and cerebellum. The findings demonstrate age-dependent developmentally dissociated neural networks for time discrimination. With increasing age there is progressive recruitment of later maturing left hemispheric and lateralized fronto parieto-striato-thalamic networks, known to mediate time discrimination in adults, while earlier developing brain regions such as ventromedial prefrontal cortex, limbic and paralimbic areas, and cerebellum subserve fine-temporal processing functions in children and adolescents. PMID- 22087092 TI - Interstitial granulomatous dermatitis: another clinical variant. AB - A 70-year-old female patient presented with an eruption consisting of symmetrically distributed erythematous papules around the umbilicus 1 month after the cessation of adalimumab for the treatment of rheumatoid arthritis. Biopsy of a papule showed an interstitial granulomatous infiltrate in the dermis, without deposition of mucin. The lesions cleared only after re-initiation of treatment 2 months later. Interstitial granulomatous dermatitis is thought to be a distinct histopathological pattern, either drug induced or associated with rheumatoid arthritis or autoimmune collagen diseases. In our case, there was a distinct clinical presentation of interstitial granulomatous dermatitis, composed of symmetrically distributed indurated papules around the umbilicus as well as a mild granulomatous reaction pattern. PMID- 22087093 TI - Kyrle disease and acquired perforating collagenosis secondary to chronic renal failure and diabetes mellitus. AB - A 59-year-old man with chronic renal failure and diabetes mellitus presented with pruritic crusted lesions which histologically were perforating disorders, showing features of both Kyrle disease and acquired perforating collagenosis. The mechanisms of transepidermal elimination and the classification of perforating disorders are briefly discussed. Additionally, we question the concept of perforation, as epidermal damage and exposure of subepidermal substances may artificially present as perforation. PMID- 22087094 TI - Recurrent Syncope due to Esophageal Squamous Cell Carcinoma. AB - Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus by metastases of a carcinoma of the esophagus, successfully treated by radiotherapy. In such cases, surgery, chemotherapy or radiotherapy can be performed. Because syncope may be an early sign of neck or cervical cancer, the diagnostic approach of syncope in patients with a past history of cancer should include the possibility of neck tumor recurrence or metastasis and an oncologic workout should be considered. PMID- 22087095 TI - Synchronous Detection of Hairy Cell Leukemia and HIV-Negative Kaposi's Sarcoma of the Lymph Node: A Diagnostic Challenge and a Rare Coincidence. AB - Hairy cell leukemia (HCL) is an uncommon chronic lymphoproliferative disorder and accounts for around 2% of all forms of leukemias. The association of HCL with other neoplasms, mainly non-Hodgkin's lymphomas, is well known. However, the simultaneous diagnosis of HCL and Kaposi's sarcoma is rare, with only few cases of such an association having been reported. We describe a 42-year-old male patient with a well characterized HCL and in whom HIV-negative Kaposi's sarcoma of the lymph node was detected. PMID- 22087096 TI - Near Total Regression of Diffuse Brain Metastases in Adenocarcinoma of the Lung with an EGFR Exon 19 Mutation: A Case Report and Review of the Literature. AB - We report the case of a woman with diffuse brain metastases from lung cancer who experienced total regression of the metastases under gefitinib treatment. The 58 year-old woman was referred to our hospital with a complaint of severe headache. A brain MRI revealed diffuse metastatic lesions in the cerebra and cerebellum. Adenocarcinoma of the lung with multiple brain metastases was diagnosed. The tumor was positive for an epidermal growth factor receptor (EGFR) exon 19 deletion mutation. She was treated with gefitinib 250 mg per day. One year later, the diffuse brain metastases had totally resolved. EGFR-tyrosine kinase inhibitor therapy could be a first-line treatment for patients with advanced adenocarcinoma of the lung with EGFR mutation, especially in those with brain metastases. PMID- 22087097 TI - An unusual case of locally advanced glycogen-rich clear cell carcinoma of the breast. AB - Glycogen-rich clear cell (GRCC) is a rare subtype of breast carcinoma characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. We present the case of a 55-year-old woman with a palpable mass in the right breast and clinical signs of locally advanced breast cancer (LABC). The diagnosis of GRCC carcinoma was based on certain histopathological characteristics of the tumor and immunohistochemical analysis. To our knowledge, this is the first case of GRCC LABC with intratumoral calcifications. There is no evidence of recurrence or metastatic disease after 14 months' follow-up. PMID- 22087098 TI - Small bowel adenocarcinoma presenting with refractory iron deficiency anemia - case report and review of literature. AB - Cancers of the small bowel are relatively rare and account for approximately 1-2% of all gastrointestinal neoplasms. The most common histologic subtype - adenocarcinoma - constitutes 40% of all cases. These cancers generally present with vague abdominal discomfort and are often diagnosed at a late stage and carry a poor prognosis. The treatment of choice of early-stage small bowel adenocarcinoma is surgical resection. No standard treatment protocol has been defined for unresectable or metastatic disease. Here, we report a case of a 56 year-old woman who presented with unexplained iron deficiency anemia. Extensive initial studies with serial CT scans of the abdomen, esophagogastroduodenoscopy, small bowel capsule endoscopy and colonoscopy were noncontributory. She was later found to have a metastatic small bowel adenocarcinoma and treated with palliative chemotherapy. She achieved a modest response to the treatment. Interestingly, in our case, the sole presentation was unexplained iron deficiency anemia. Physician's awareness regarding the possibility of small bowel cancer especially in the setting of iron deficiency and its workup has been emphasized. This enhances the chance of early detection and hence better survival. PMID- 22087099 TI - Subacute Neurological Deterioration with Selective Axonal Injury in Patients with Acute Ischemic Stroke following Reperfusion of Middle Cerebral Artery Occlusion. AB - To date, the long-term effects of reperfusion on the salvaged brain tissues have not been addressed in the literature. We report 4 cases presenting subacute neurological deteriorations with selective axonal injury following reperfusion therapies for acute ischemic stroke. Our case series based on 4 patients showed common features distinct from those of early reperfusion injury in that (1) the neurological symptoms developed after 1-2 months of reperfusion therapies, (2) these symptoms were accompanied by the subcortical white matter changes on brain MRI, and (3) these findings were mostly reversible with time. This suggests that axons in the reperfused brain may be vulnerable to further neurological injury. PMID- 22087100 TI - Thrombolytic stroke treatment of a 12-year-old girl with intracranial fibromuscular dysplasia. AB - Fibromuscular dysplasia, predominantly found in adult women, is a rare disease of small and middle-sized arteries of the kidney and brain. We present a case of a 12-year-old girl with acute ischemic stroke, due to fibromuscular dysplasia of the distal internal carotid artery and the proximal middle cerebral artery, which was successfully treated with t-PA. PMID- 22087101 TI - Serous macular detachment associated with dome-shaped macula and tilted disc. AB - INTRODUCTION: An entirely new type of staphyloma has been recently described as dome-shaped macula (DSM). It is characterized by an abnormal convex macular contour within the concavity of a posterior staphyloma. We found DSM associated with serous macular detachment (SMD) and tilted disc in two consecutive cases. CASE REPORTS: Case 1: A 37-year-old female presented to our department because of sudden onset blurred vision in her right eye (OD). The best-corrected visual acuity (BCVA) was 0.5 in both eyes. Funduscopy evidenced bilateral tilted disc associated with posterior staphyloma. Optical coherence tomography (OCT) demonstrated a DSM with SMD in her OD. After 15 months of follow-up, BCVA of her OD remained stable with chronic SMD. Case 2: A 32-year-old female presented to our department because of blurred vision in her OD. The BCVA was 0.4 in the OD and 1.0 in the left eye (OS). Bilateral tilted disc and posterior staphyloma were evidenced in the funduscopy. OCT demonstrated a bilateral DSM with SMD in her OD. After 45 months of follow-up, two further episodes of transient SMD were observed in her OD and seven in her OS. The final BCVA was 0.63 in the OD and 0.8 in the OS. DISCUSSION: SMD associated with tilted disc constitutes a potential cause of subretinal fluid accumulation in myopic patients. OCT is essential for the detection of both SMD and DSM. PMID- 22087102 TI - White centered retinal hemorrhages in vitamin b(12) deficiency anemia. AB - BACKGROUND: To report a case of severe vitamin B(12) deficiency anemia presenting with white centered retinal hemorrhages. METHODS: Interventional case report. RESULTS: A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B(12) deficiency requiring erythrocyte transfusions. DISCUSSION: Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B(12) deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture. PMID- 22087103 TI - A Novel Compound Heterozygous Mutation in the CYP4V2 Gene in a Japanese Patient with Bietti's Crystalline Corneoretinal Dystrophy. AB - PURPOSE: To describe the clinical and genetic characteristics of a Japanese family in which one member exhibited Bietti's crystalline corneoretinal dystrophy (BCD). METHODS: Using direct sequencing, mutation screening was performed in the CYP4V2 gene of both the patient with BCD and her daughter. Ophthalmic examinations were performed to determine the clinical features of both subjects. RESULTS: The 64-year-old female patient had a bilateral visual acuity of 0.4. Slit lamp examination revealed bilateral crystalline-like deposits at the superior limbus of the cornea. Fundus examination revealed there was chorioretinal atrophy along with numerous glistening yellowish-white crystalline deposits that were scattered throughout the posterior pole and the mid-peripheral retina. Standard flash electroretinography showed an extinguished electroretinogram and Goldmann kinetic perimetry detected a relative scotoma. Genetic analysis revealed that the patient had a heterozygous mutation in the CYP4V2 gene (IVS6-8delTCATACAGGTCATCGCG/GC), which is the most commonly found mutation in Japanese patients with BCD. Furthermore, the patient was also shown to have a novel heterozygous point mutation in exon 9 of the CYP4V2 gene (c.1168C>T). In contrast, her daughter exhibited no clinical findings for BCD even though she carried the same heterozygous mutation in the CYP4V2 gene (c.1168C>T). CONCLUSION: A novel compound heterozygous mutation was found in the CYP4V2 gene of a patient with BCD. This previously unreported c.1168C>T mutation causes a missense mutation (p.R390C) in the CYP4V2 protein. PMID- 22087104 TI - Bilateral corneal ulceration caused by vitamin a deficiency in eosinophilic gastroenteropathy. AB - PURPOSE: Vitamin A deficiency is a very rare condition in the developed world and can lead to a variety of ocular changes from xerosis and xerophthalmia to corneal ulcer and perforation. The treatment of this devastating disease is simple and inexpensive. It is therefore important to recognize and treat accordingly, especially in the event of ulcers unresponsive to treatment or in the presence of severe malnutrition/malabsorption syndromes. The purpose of this case report is to remind physicians of the potentially devastating effects of vitamin A deficiency on the eyes and to demonstrate outcomes after vitamin A treatment. METHODS: Single observational case report. RESULTS: A 29-year-old male with known eosinophilic gastroenteropathy was treated with oral steroids for peripheral ulcerative keratitis. Two weeks after resolution, the patient suffered from peripheral ulcerative keratitis in his other eye, with a self-sealing perforation. Vitamin A deficiency was confirmed and successfully treated, leading to subsequent resolution of signs and symptoms. CONCLUSIONS: Vitamin A deficiency can be present in patients with malabsorption and malnutrition syndromes and should be considered as cause of corneal ulceration. PMID- 22087105 TI - Acetaminophen: beyond pain and Fever-relieving. AB - Acetaminophen, also known as APAP or paracetamol, is one of the most widely used analgesics (pain reliever) and antipyretics (fever reducer). According to the U.S. Food and Drug Administration, currently there are 235 approved prescription and over-the-counter drug products containing acetaminophen as an active ingredient. When used as directed, acetaminophen is very safe and effective; however when taken in excess or ingested with alcohol hepatotoxicity and irreversible liver damage can arise. In addition to well known use pain relief and fever reduction, recent laboratory and pre-clinical studies have demonstrated that acetaminophen may also have beneficial effects on blood glucose levels, skeletal muscle function, and potential use as cardioprotective and neuroprotective agents. Extensive laboratory and pre-clinical studies have revealed that these off-label applications may be derived from the ability of acetaminophen to function as an antioxidant. Herein, we will highlight these novel applications of acetaminophen, and attempt, where possible, to highlight how these findings may lead to new directions of inquiry and clinical relevance of other disorders. PMID- 22087106 TI - Hepatic granulomas associated with brucellosis: Hepatic granulomas and brucellosis. PMID- 22087107 TI - Halothane-induced hepatitis: A forgotten issue in developing countries: Halothane induced hepatitis. AB - Halothane was introduced as an anesthetic in the 1950s and was considered a revolutionary agent in the field of anesthesia. Soon after, halothane-induced hepatitis became a concern, leading to the development of less toxic gases that induced a lower incidence of side effects. Two types of halothane-related hepatotoxicity have been described: type 1, or mild hepatitis, is associated with elevated transaminase levels and self-limiting symptoms, and type 2, or severe hepatotoxicity, is associated with acute fatal liver failure and is fatal in most cases. Hepatotoxicity is most likely to be immune-related, based on much evidence. Free radicals that are produced by the metabolism of halothane in the liver can modify cellular proteins and introduce neo-antigens to the immune system. Sensitization to these neo-antigens induces a more severe response after multiple exposures; most cases of type 2 hepatitis occur after repeated contact. New halogenated anesthetics such as enflurane, sevoflurane, and desflurane, are not metabolized in the liver, causing few cases of sensitization. Compared with halothane, these anesthetics are expensive. As a result, replacement of halothane with new halogenated anesthetics requires a precise cost-benefit analysis, especially in developing countries that have low health care budgets. PMID- 22087108 TI - Occult hepatitis B virus infection: A major concern in HIV-infected patients: Occult HBV in HIV. AB - Human immunodeficiency virus (HIV)- infected patients are at risk of acquiring viral hepatitis, due to common routes of transmission. As the introduction of highly active antiretroviral therapy (HAART) reduced the frequency of opportunistic infections and improved survival, viral hepatitis emerged as an important cause of morbidity and mortality in HIV-infected cases. Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection without detectable hepatitis B surface antigen (HBsAg). There are conflicting reports on the impact of occult HBV infection on the natural history of HIV disease. In this review, we described the findings of studies on HIV and hepatitis B co-infection with focus on the prevalence of occult HBV infection. The results of this review demonstrated the importance of prevention, diagnosis and treatment of occult HBV infection in HIV-positive patients. PMID- 22087109 TI - Comparison of the prevalence of major transfusion-transmitted infections among Iranian blood donors using confidential unit exclusion in an Iranian population: Transfusion-transmitted infections among Iranian blood donors. AB - BACKGROUND: Nucleic acid amplification testing is recommended for screening blood donations; however, they are not widely available in developing countries such as Iranian. Confidential unit exclusion (CUE) gives blood donors the opportunity to confidentially indicate whether their blood is or is not suitable for transfusion to others. Hoewever, its effectiveness in improving blood safety has recently been questioned by the blood banking community. OBJECTIVES: The purpose of this study was to determine the efficacy of CUE in Iran. PATIENTS AND METHODS: Data on transfusion-transmitted disease markers (HBs Ag, HCV Ab, HIV Ab, RPR) were extracted from a database of voluntary blood donations in 2006 at the Tehran Blood Transfusion Center. The prevalence of markers were compared between CUE positive ("should not use") and CUE-negative ("can be used") donations. RESULTS: CUE-positive donations had significantly higher risk of HBV and HCV markers (odds ratio (95% confidence interval)7.5 (5.4-10.5) and 5.3 (2.5-11.3), respectively). No HIV or syphilis markers were detected in either group. CONCLUSIONS: CUE is an effective option for identifying donors with increased risk of HBV and HCV markers. PMID- 22087110 TI - A study of genotypes, mutants and nucleotide sequence of hepatitis B virus in Pakistan: HBV genotypes in pakistan. AB - BACKGROUND: Hepatitis B virus (HBV) genotypes and mutations are gaining importance in determining the clinical course of chronic liver disease. OBJECTIVES: To determine and compare the distribution of HBV genotypes and genomic variations in Pakistan to other parts of the world. PATIENTS AND METHODS: We conducted a prospective study at Aga Khan University Hospital from December 2006 to December 2008. HBV genotype was determined in 257 HBV DNA-positive patients. Patients were divided into two groups according to HBeAg positivity. Mutations in the pre-core and core promoter regions of HBV were determined in HBeAg-negative patients by line probe INNOLIPA assay. RESULTS: The mean+/-SD age of patients was 28+/-5 years; there were 201 (78%) men. HBeAg was positive in 219 (85%) patients and negative in 38 (15%). HBeAg-positive patients were younger than HBeAg-negative patients (95% vs 21% in <=30 years, p<0.001). HBV genotype D found in 247 (96.2 %) patients followed by a combined infection with HBV genotype B+D in 9 (3.3%) and 1 (0.5%) with genotype A. The mutations identified in 38 HBeAg-negative patients were T1762/A1764 in 21 (55.2%), PC mutant in 7 (18.4%), T1762/A1764/PC mutant in 2 (5%) and T1762/A1764/PC wild mutation in 1 (2%); no mutation identified in 7 (18.4%). Phylogenetic analysis did not show any significant differences between HBV genotype D isolated from Pakistan and those isolated from other parts of the world. CONCLUSIONS: HBV genotype D is predominant in Pakistan, irrespective of HBeAg status. PC and BCP mutations were found in significant numbers of patients infected with genotype D. The HBV genotype D isolates from Pakistan are identical to the sequences isolated from other parts of the world. PMID- 22087111 TI - Incarceration is a major risk factor for blood-borne infection among intravenous drug users: Incarceration and blood borne infection among intravenous drug users. AB - BACKGROUND: There is a strong association between hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection which are mainly transmitted by contamination with blood via intravenous drug abuse (IVDU) or sexual contact. OBJECTIVES: To determine the prevalence of these infections and the risk factors associated with them among prisoner and non prisoner IVDUs in Tehran, Iran. PATIENTS AND METHODS: This cross-sectional study was performed in two jails and three drug rehabilitation centers between 2001 and 2002 in Tehran. HBsAg and HBcAb were checked using highly specific third generation enzyme immunoassays (DIA.PRO, Italy, specificity >99%, and Radim, Italy, specificity 99.7%, respectively). HCVAb was detected using ELISA (DIA.PRO, Italy) with both sensitivity and specificity >98%. HIVAb test (DRG Diagnostics kit, Germany) was performed for 459 of the 468 IDU subjects. RESULTS: 392 prisoners and 135 individual attending drug rehabilitation centers were approached. Of the 518 subjects studied, 464 (89.5%) were male, 386 (74.5%) were prisoners and 132 (25.5%) were non-prisoners. In this study, HBsAg, HCVAb and HIVAb were positive in 19 (3.7%), 359 (69.5%) and 70 (15.5%) of subjects, respectively. These tests were positive in 17 (4.5%), 311 (80.5%) and 63 (17%) among prisoners and 2 (1.5%), 48 (36.5%) and 7 (7.8%) in non-prisoners, respectively. Multiple logistic regression analysis revealed that independent factors related to co-infection of HCV and HIV infection were imprisonment (p<0.001. OR: 7.5) and using common syringe (p=0.03, OR: 4.5). CONCLUSIONS: Our findings strongly suggest that drug injection inside prison carries is a risk for HIV infection and that HIV infection among IDUs is likely to be bridged to the broader population through sexual contact without using effective prevention programs. PMID- 22087112 TI - Polymorphisms within Fas gene are not associated with occult hepatitis B virus infection: Polymorphisms within Fas gene in occult HBV infection. AB - BACKGROUND: Occult hepatitis B infection (OBI) is a form of hepatitis in which there is an absence of detectable HBsAg, despite the presence of HBV-DNA in the peripheral blood of patients. It seems that non-effective or attenuated immune system responses against HBV lead to the development of OBI. Previous studies showed that the Fas/Fas ligand (FasL) system is an important death signaling pathway that is used by cytotoxic T lymphocytes to eradicate HBV from the liver. OBJECTIVES: To investigate polymorphisms in the -670 region of the Fas gene in those with OBI. PATIENTS AND METHODS: The plasma samples from 3700 blood donors were tested for HBsAg and anti-HBs by ELISA. The HBsAg-/anti-HBc(+) samples were selected and screened for HBV-DNA by PCR. Those with HBV-DNA were diagnosed as OBI and PCR-RFLP technique was performed to examine polymorphisms within their Fas gene. RESULTS: 352 (9.5%) of 3700 blood samples were HBsAg-/anti-HBc(+). HBV DNA was detected in 57 (16.1%) of 352 HBsAg-/anti-HBc(+) samples. Therefore, 57 HBsAg-/anti-HBc+/HBV-DNA(+) patients were diagnosed as OBI. Patient and control groups had no significant differences in terms of the studied polymorphisms. CONCLUSIONS: The functional polymorphisms in the promoter region of Fas gene are not associated with OBI. Therefore, it may be concluded that polymorphisms at the -670 position of the Fas gene do not have any critical effects on the immune response against HBV in OBI. PMID- 22087113 TI - A comparison of treatment with adefovir and entecavir for chronic hepatitis B in China: The 2-year results of a prospective study: Adefovir versus Entercavir for Chronic Hepatitis B. AB - BACKGROUND: The reduction of hepatitis B virus replication to minimal levels is emerging as key therapeutic goal in chronic hepatitis B (CHB). OBJECTIVES: This study aimed to evaluate and compare the efficacies of adefovir (ADV) and entecavir (ETV) in CHB. PATIENTS AND METHODS: In this prospective study, 100 naive patients were assigned to treatment with ADV (33 HBeAg-positive and 19 HBeAg-negative patients) or ETV (32 HBeAg-positive and 16 HBeAg-negative patients). The primary efficacy outcome was ALT normalization, reduction in HBV DNA, and seroconversion of HBeAg. Second efficacy outcomes included resistance and safety. Comparisons of quantitative and qualitative variables between groups were analyzed by student t-test and chi-square test (or Fisher's exact test), respectively. RESULTS: Among HBeAg-positive patients, ETV was superior to ADV with respect to mean reduction in HBV DNA (-7.5 versus -6.3, respectively, at Month 24, p = 0.003) and the percentage of those with HBV DNA < 103 copies/mL at Month 24 [96.9% (31/32) vs. 69.7% (23/33), respectively, p = 0.002] and < 300 copies/mL at Month 24 [84.4% (27/32) vs. 54.5% (18/33), respectively, p = 0.004]. But, the rates of ALT normalization and HBeAg seroconversion between the groups were similar [87.9% (29/33) vs. 96.9% (31/32), respectively, p=0.355; and 24.2% (8/33) vs. 25.0% (8/32), respectively, p = 0.943]. In HBeAg-negative patients who received ETV or ADV, the reduction in HBV DNA (-6.8 versus -5.9, respectively, p = 0.192), percentage of ALT normalization [100% (16/16) vs. 78.9% (15/19), respectively, p=0.109], HBV DNA < 103 copies/mL [100% (16/16) vs. 89.5% (17/19), respectively, p = 0.489], and HBV DNA < 300 copies/mL [100% (16/16) vs. 84.2% (16/19), respectively, p = 0.234] were similar. No ETV- or ADV-associated mutations were observed, and both agents were well tolerated. CONCLUSIONS: ETV and ADV are effective therapies for CHB. In HBeAg-positive patients, the efficacy of ETV is significantly superior to that of ADV, and in HBeAg-negative patients, the agents effect similar biochemical and virological responses. PMID- 22087114 TI - The effect of zinc sulfate on immunologic response to recombinant hepatitis B vaccine in elderly: Zinc sulfate and immunologic response to recombinant hepatitis B vaccine. AB - BACKGROUND: Hepatitis B is the major cause of chronic hepatitis and cirrhosis in Iran. Sanitation and immunization is one of the most effective measures for prevention of the disease which is now widely used in developing countries. However, the immune response to the vaccine varies by age. OBJECTIVES: To determine the effect of zinc sulfate on immune response to hepatitis-B vaccine in elderly. PATIENTS AND METHODS: In a clinical trial on 140 subjects aged ?40 years with a body mass index (BMI) <30 kg/m2, and without any co-morbid disease were recruited. Those who had negative hepatitis B core antibody (102 persons) were randomly allocated to two groups. The trial group received hepatitis B vaccine plus 200 mg zinc sulfate daily for 30 days and the control group received vaccine plus placebo. RESULTS: 52 of 102 people were female (51%). The two studied groups were comparable in terms of age, gender, and smoking habits. The mean antibody production in the intervention and control groups was 116.93 and 157.37 mIU/mL, respectively (p=0.22). No statistical differences were observed between the two groups in terms of proportion of people who were protected after vaccination (26.0% and 36.5% in people with and without zinc, respectively). CONCLUSIONS: This study revealed that zinc sulfate has no effect in level of immunity among elderly. PMID- 22087115 TI - Commentary on the article: Are hepatitis B virus and celiac disease linked?: HBV and celiac disease. PMID- 22087116 TI - Are nonintestinal inflammatory diseases and celiac disease linked?: Nonintestinal inflammatory and celiac disease. PMID- 22087117 TI - Commentary on: Are hepatitis B virus and celiac disease linked?: HBV and Celiac Disease. PMID- 22087118 TI - Hepatitis B virus and celiac disease: HBV and Celiac Disease. PMID- 22087119 TI - Celiac disease and hepatitis B virus: Celiac disease and HBV. PMID- 22087120 TI - Dilemma of HBsAg seroconversion in chronic hepatitis B infection: Dilemma of HBsAg in chronic HBV. AB - Patients with chronic hepatitis B infection should be followed up to identify possible changes in disease status, such as HBsAg seronversion. There are little data on the outcome of such cases, and the response rate to HBV vaccine has not been discussed extensively. PMID- 22087121 TI - Hepatocellular carcinoma: HCC. PMID- 22087122 TI - Hepatitis C and pulmonary fibrosis: Hepatitis C and pulmonary fibrosis. AB - BACKGROUND: Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus that causes hepatic and extrahepatic disease. Emerging clinical data suggest that chronic HCV infection can lead to many direct and indirect effects on the lung. OBJECTIVES: This article discusses evidence on the relationship between HCV infection and pulmonary fibrosis to increase knowledge on this topic among clinicians and scientists and highlights the need for further study. METHODS: We searched the MEDLINE, ISI WEB OF KNOWLEDGE, OVID, ELSEVIER, and MDCONSULT databases and top respiratory journals, such as the American Journal of Respiratory and Critical Care, Chest, and Thorax for articles in English using the following keywords: hepatitis C, HCV infection, IPF, pulmonary fibrosis, and interstitial pneumonitis. We reviewed the reference lists of all identified studies. RESULTS: The evidence for a pathogenetic link between pulmonary fibrosis and HCV is: the higher frequency of HCV markers in IPF patients, an increase in lymphocyte and neutrophil numbers in bronchoalveolar lavage of chronic HCV infection patients, and the development of IPF in HCV-related chronic hepatitis that is treated with interferon. There is a discrepancy between studies on the frequency of HCV in IPF patients, which might be attributed to geographical differences of in the prevalence of HCV infection, selection bias in choosing the control group, and the HCV genome. CONCLUSIONS: BAL studies in HCV infection are associated with increased counts of lymphocytes and neutrophils in BAL fluid. These studies show that HCV infection is associated with nonspecific pulmonary inflammatory reactions that are not compatible with IPF but that it can lead to pulmonary fibrosis. The other factor is interferon therapy. Interstitial pneumonia and sarcoidosis are well-documented complications of IFN therapy. More extensive cohort studies should be conducted to confirm an actual causal relationship between HCV infection and pulmonary fibrosis. PMID- 22087123 TI - Genotypes, mutations, and viral load of hepatitis B virus and the risk of hepatocellular carcinoma: HBV properties and hepatocarcinogenesis. AB - Chronic infection with hepatitis B virus (HBV) is the major risk factor for hepatocellular carcinoma (HCC) worldwide. Ten HBV genotypes (A-J) have been discovered so far. Genotypes B and C are endemic in East and Southeast Asia. Genotype C HBV is associated with increased risks of cirrhosis and HCC. Genotype B (B2) is associated with the development of HCC in non-cirrhotic patients younger than 50 years and with relapse of HCC after surgical treatment. It is also associated with earlier hepatitis B e antigen seroconversion than genotype C. High HBV load is independently associated with the occurrence and post treatment recurrence of HCC. Different genotypes have distinct patterns of mutations. Viral mutations in the core promoter region and in the preS region are frequently found to be significantly associated with an increased risk of HCC. These mutations often occur before the onset of HCC and accumulate during the progression of chronic HBV infection. Multiple such mutations are more frequent in patients with HCC and are specific for HCC. HBV subgenotypes, viral mutations, and viral load can be used for the prediction of HCC. Early identification of HBV infected individuals who will eventually develop HCC will help to develop active prophylactic protocols to reduce or delay the occurrence of HCC. PMID- 22087124 TI - Rosuvastatin reduces nonalcoholic fatty liver disease in patients with chronic hepatitis C treated with alpha-interferon and ribavirin: Rosuvastatin reduces NAFLD in HCV patients. AB - BACKGROUND: Nonalcoholic fatty liver disease develops in patients with chronic hepatitis C. Interferon and ribavirin combination therapy is the standard treatment for chronic hepatitis C, but if present, NAFLD can reduce the virological response to anti-HCV therapies. OBJECTIVES: We determined whether the addition of rosuvastatin to interferon and ribavirin improves the sustained virological response (SVR) and reduces steatosis. PATIENTS AND METHODS: This study was a prospective, randomized, open-label trial. Between January 2004 and December 2007, 65 patients with chronic hepatitis (27 women and 38 men, mean age 48 years) aged 32-63 years (median 46 years) were consecutively enrolled. Patients were randomly assigned to receive leukocyte interferon alpha (3 MIU 3 times per week) plus ribavirin (1200 mg per day) for 12 months or interferon alpha and ribavirin at the same dosages plus rosuvastatin (5 mg per day). The primary endpoints were measurements in SVR, liver enzyme, cholesterol, triglyceride, CRP, glucose, and insulin levels; and Homa-IR, fibrosis, and steatosis scores. RESULTS: After 12 months of treatment, we observed a significant improvement in SVR in 51% of patients who received interferon plus ribavirin plus rosuvastatin compared with 18% of relapsers (OR 1.52; 95% CI = 0.41-5.64; RR 1.13). There were 23 responders (69%) and 10 nonresponders (30%) (OR 1.38; 95% CI = 0.49-16.5; RR 1.11). When comparing interferon plus ribavirin group vs interferon plus ribavirin and rosuvastatin group after 12 months, we observed a significant difference in AST (85.70 vs.106.5.00 IU/ml) (OR 1.2; 95% CI= 0.29-4.94; RR 1.04; p<0.001), ALT (81.80 vs. 126.2 IU/ml) (OR 1.2; 95% CI = 0.29-4.94; RR 1.04; p < 0.001), LDL-cholesterol (0.01 vs. 0.60 mmol/l) (OR 14; 95% CI = 3.98-49.16; p RR 2.96; < 0.001), triglycerides (0.17 vs. 0.2 mmol/l) (OR 20; 95% CI = 4.94-80.89; RR 5.38; p < 0.05), and Viremia (1.8 vs. 2.48 UI/ml, p < 0.05). Mean fibrosis score decreased 0.10 vs. 0.50 (OR 4.5; 95% CI = 0.89-22.66; RR 1.5; p < 0.05), and mean steatosis score declined 0.30 vs. 0.50 (OR 11.2; CI = 2.88-43.53; RR 2.75; p < 0.001). CONCLUSIONS: In HCV patients with NAFLD, the addition of rosuvastatin to interferon and ribavirin significantly reduces viremia, steatosis, and fibrosis without causing side effects. PMID- 22087125 TI - Anti-HBs antibody status and some of its associated factors in dental health care workers in Tehran University of Medical Sciences: Anti-HBs Ab and associated factors in dental society. AB - BACKGROUND: Dental health care providers are at risk of infection with hepatitis B virus (HBV). Dentists can occupationally become infected with HBV through needle sticks or exposure to blood and other body fluids. OBJECTIVES: To evaluate anti-HBs antibody titer in students, professors, clinical assistants and non clinical staff of Faculty of Dentistry, Tehran University of Medical Sciences (TUMS), and to investigate the probable correlation between the level of immunity and a number of associated factors. PATIENTS AND METHODS: 230 participants who had a history of previous HBV vaccination (receiving at least two doses of HBV vaccine) and a negative history of being infected with HBV were studied. Participants' data were recorded using a checklist, and the level of antibody was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: While there existed statistically significant correlations between age, occupation, smoking, complete and scheduled vaccination and time of the last vaccination with the level of anti-HBs antibody, the correlation between gender and level of the antibody was not significant. Multiple regression analysis revealed significant association between immune response and age and time of the last vaccination. CONCLUSIONS: Due to the significant correlation between younger age and anti-HBs antibody titer in our study, it makes sense to establish a mandatory complete and scheduled vaccination program for all members of dental society younger than 40 years. PMID- 22087126 TI - Noninvasive assessment of liver fibrosis with the aspartate transaminase to platelet ratio index (APRI): Usefulness in patients with chronic liver disease: APRI in chronic liver disease. AB - BACKGROUND: The aspartate aminotransferases (AST) to platelet ratio index (APRI) may serve as a noninvasive marker to assess liver fibrosis. OBJECTIVES: To assess the diagnostic ability of the APRI for prediction of fibrosis in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: This retrospective study included 207 patients with CHB, 108 with CHC, and 140 patients with NAFLD. The APRI was calculated as (AST level/upper normal limit for AST)/platelet counts (109/L) * 100. The stage of liver fibrosis in patients with chronic viral hepatitis was graded using the METAVIR scale. The Kleiner system for grading fibrosis was used in patients with NAFLD. RESULTS: Bivariate correlation analyses showed that the APRI was significantly associated with fibrosis scores in patients with CHC (p = 0.2634, p = 0.0059) and NAFLD (p = 0.2273, p = 0.0069), but not in those with CHB (p = 0.1005, p = 0.1495). Receiver operating characteristic (ROC) curves were used for assessing the ability of the APRI as a predictor of the absence or presence of liver fibrosis (fibrosis score of 0 vs fibrosis scores of 1-4). In patients with CHC, the APRI showed a sensitivity of 72.7% and a specificity of 62.4% for detection of fibrosis (p<0.01). In the NAFLD group, the APRI showed a sensitivity of 60.0% and specificity of 73.3% for detection of fibrosis (p<0.01). In patients with CHB, the APRI showed a sensitivity of 55.0% and a specificity of 75.4% for fibrosis (p=NS). CONCLUSIONS: The APRI shows an acceptable accuracy for the assessment of liver fibrosis in patients with CHC and NAFLD, but not in those with CHB. PMID- 22087128 TI - Efficacy of Hepatitis B vaccine in those who lost Hepatitis B surface antigen during follow-up: Efficacy of HBV vaccine in those who lost HBsAg. AB - BACKGROUND: The level of HBsAg in some chronic hepatitis B virus (HBV)-infected individuals may decline over time so that it is not detectable in serum. OBJECTIVE: To assess the efficacy of HBV vaccine in those who lost their HBsAg without seroconverssion to anti-HBs antibody. PATIENTS AND METHODS: From April 1993 to December 2008, of 1603 chronic HBV-infected individuals, 34 (22 men and 12 women) became HBsAg-negative in follow-up visits, with no detectable anti-HBs antibody and HBV DNA in their sera. They received HBV vaccination at 0, 1 and 6 months (case group). Fifty-two subjects (30 men and 22 women) who were negative for HBsAg, anti-HBs and anti-HBc antibody, received HBV vaccination according to the said schedule (control group). Anti-HBs antibody was assessed one month after the last dose of vaccination in the both groups. RESULTS: The mean+/-SD age of the case and control groups was 38+/-12.7 and 33.4 +/- 8.6 years, respectively (p = 0.07). The sex distribution between these two groups were similar (p = 0.652). The mean +/- SD years of follow-up for the case group was 7.6 +/- 4.5 years. Anti HBs antibody level >= 10 IU/L was found in 8 (24%) subjects in the case group and in 45 (87%) in the control group (p < 0.001). The mean+/-SD anti-HBs antibody level in the case group was 68 +/- 32.66 and in the control group 344.6 +/- 38.9 IU/L (p < 0.001). CONCLUSIONS: We found that nearly 24% of chronic HBsAg-positive subjects who lost their HBsAg responded to HBV and the remaining cases need to be followed for occult HBV infection. PMID- 22087129 TI - Idiopathic hypereosinophilic syndrome presenting with liver mass: Report of two cases: Idiopathic hypereosinophilic syndrome and liver mass. AB - Herein, we report on two cases of hypereosinophilic syndrome presenting as liver mass. One patient was a 22-year-old woman presented with fever, upper abdominal pain, nausea/vomiting and a mass in the right liver lobe. The second patient was a 54-year-old man who presented with nausea and abdominal pain with significant weight loss. He had multiple lesions in both liver lobes. Both patients had eosinophilia that was not attributed to other causes such as allergy or parasites. The patients were treated with glucocorticosteroid and improved clinically. Imaging and laboratory abnormalities resolved. PMID- 22087127 TI - Reversible autonomic dysfunction during antiviral treatment in patients with chronic hepatitis C virus infection: Anti-HCV therapy and autonomic function. AB - BACKGROUND: The first clinical sign of chronic hepatitis C virus (HCV) infection can be one of the various extrahepatic manifestations. During antiviral treatment, symptoms of HCV-associated neuropathies usually improve, but can also worsen and lead to discontinuation of anti-HCV therapy. Recently, we have reported autonomic dysfunction in patients with HCV infection. OBJECTIVES: In the present prospective study, we analyzed the changes of autonomic function during anti-HCV treatment. PATIENTS AND METHODS: Cardiovagal autonomic function was assessed in 22 HCV RNA-positive, treatment-naive patients by determining heart rate variability (HRV) and baroreflex sensitivity (BRS), at the beginning of treatment and 12, 24 and 48 weeks of antiviral therapy. interferon alfa-2 and ribavirin were given according to the guidelines. RESULTS: Both HRV and BRS time and frequency domain indices decreased after 12 weeks of therapy compared to the pre-treatment values; then the mean+/-SD values increased significantly by week 24 and continued to improve by week 48 of therapy-253.0+/-156.1 ms before therapy vs 111.6+/-81.9 at week 12, and 183.4+/-169.6 at week 24 vs 211.6+/-149.1 ms at week 48 for low-frequency HRV index; p<0.05 for all comparisons). These changes were independent from the presence of cryoglobulins and from virologic response. CONCLUSIONS: The first rise followed by reversible autonomic dysfunction during antiviral therapy may be caused by the immunomodulatory actions of interferon alfa-2. PMID- 22087130 TI - The relationship between celiac disease and hepatitis B virus: celiac disease and HBV. PMID- 22087131 TI - Occult hepatitis B infection in chronic hemodialysis patients: Comparison of results and concepts: Occult HBV in chronic hemodialysis patients. PMID- 22087132 TI - Seroprevalence of anti-HDV Ab and socioepidemiological characteristics among HBsAg-positive blood donors in Charmahal-o-Bakhtiyari province, Iran: Anti-HDV among HBsAg-positive blood donors. PMID- 22087133 TI - Association between hepatitis C virus and oral lichen planus: HCV and oral Lichen Planus. PMID- 22087134 TI - HCV and lichen planus: HCV and lichen planus. PMID- 22087135 TI - Hepatocellular recurrence after orthotopic liver transplantation: Is combination of alpha-fetoprotein and glypican-3 a reliable marker?: Hepatocellular recurrence after orthotopic liver trasplantation. PMID- 22087136 TI - Fibroscan for assessing liver fibrosis: An acceptable alternative for liver biopsy: Fibroscan: an acceptable alternative for liver biopsy. PMID- 22087137 TI - HCC, diet and metabolic factors: Diet and HCC. AB - Hepatocellular carcinoma is the most common primary liver malignancy and is an international public health concern, constituting one of the most deadly cancers worldwide. Infection with hepatitis B virus and hepatitis C virus is a major risk factor for HCC in developed countries. Emerging evidence indicates that there are other important lifestyle factors that contribute to the international burden of HCC, such as alcohol consumption, diabetes, obesity, and the intake of aflotoxin contaminated food. Obesity and diabetes are also likely to be risk factors for HCC, the most frequent subtype of liver cancer. The chief pathway by which obesity increases risk involves the association between obesity and nonalcoholic fatty liver disease (NAFLD). Coffee consumption has been studied extensively and appears to have a favorable effect on the prevention of liver diseases, including HCC. One hypothesis suggests that coffee intake lowers serum levels of gamma glutamyltransferase (GGT), which is associated with a lower incidence of HCC. It is estimated that more than 80% of HCC cases are attributable to four principal causes that are avoidable. It is difficult to make dietary recommendations, because it is unknown whether consuming higher amounts of specific antioxidants will decrease the risk of developing hepatocellular carcinoma. A diet rich that is in polyunsaturated fatty acids and, possibly, B-carotene could reduce the risk of HCC, and high dietary GL is associated with an increased risk independently of cirrhosis or diabetes. PMID- 22087138 TI - Single nucleotide polymorphisms of the IL28B and sustained virologic response of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy: A meta analysis: Meta-analysis of IL28B. AB - BACKGROUND: Hepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus (HCV) infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes. OBJECTIVES: To assess the associations of single nucleotide polymorphisms (SNP) of the IL28B and sustained virologic response (SVR) of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy. MATERIALS AND METHODS: We searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate at SNP of the IL28B in individuals with PEG interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied. RESULTS: The sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans (OR = 3.85, 95% CI: 3.06-4.83); the percentage of rs12979860 TT genotype was lower in Caucasians (OR = 0.25, 95% CI: 0.20-0.31) and the percentage of rs12979860 CC genotype was higher in Caucasians than that of Afro-Americans (OR = 3.45, 95% CI = 2.68-4.44). Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 (OR = 0.16, 95% CI: 0.11-0.24). CONCLUSIONS: IL28B is significantly associated with response to PEG interferon/ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes. PMID- 22087139 TI - Hepatitis C and hepatitis B seroprevalence and associated risk factors in hemodialysis patients in Guilan province, north of Iran: HCV and HBV seroprevalence in hemodialysis patients. AB - BACKGROUND: Hepatitis C virus (HCV) and hepatitis B virus (HBV) infection are especially problematic in patients with end-stage renal disease who are undergoing hemodialysis (HD). OBJECTIVES: To determine the prevalence of HCV and HBV infection in HD population in Guilan, north of Iran. PATIENTS AND METHODS: In a cross-sectional study, from May to September 2009, in 11 different hemodialysis units in Guilan province, North of Iran, clinical data such as age, gender, duration of dialysis, HBsAg and anti-HCV antibody of 514 HD patients were recorded. Patients with positive antibodies against HCV were tested for HCV RNA. RESULTS: From 514 patients, 286 (55.64%) were male. 61 (11.9%) patients were anti HCV-positive and 31 (50.8%) were HCV PCR-positive. There was significant relationship between HCV Ab-positivity with gender and HD duration (p < 0.05). There was significant difference between the mean HD duration in anti-HCV positive and anti-HCV-negative patients (p < 0.05). Also, significant relationship was found between HCV RNA-positivity with gender and HD duration (p < 0.05). Seven (1.4%) patients were positive for HBsAg. Two (0.38 %) were found positive for both HBsAg and anti-HCV antibody. CONCLUSIONS: There is low a prevalence of HCV and HBV in HD patients in our region. The rate can be decreased by HBV vaccination of end-stage renal disease patients before setting chronic HD, antiviral treatment and isolation of infected individuals. PMID- 22087140 TI - Assessment of noninvasive liver stiffness in inactive HBsAg carriers by transient elastography: Fibroscan in inactive HBsAg carriers. AB - BACKGROUND: Chronic viral hepatitis can be evaluated using invasive or noninvasive methods. OBJECTIVES: The aim of this study was to evaluate liver stiffness in inactive HBsAg carriers compared with normal subjects and determine if it is influenced by viral load in these patients. PATIENTS AND METHODS: We prospectively evaluated 140 inactive HBsAg carriers and 152 normal subjects (without any signs or history of liver disease). In all subjects, liver stiffness was measured by 3 experienced physicians using a FibroScan(r) device (EchoSens, France) per standard procedures. We excluded patients for whom the SR of liver stiffness measurements was < 60% and those who had measurements with an IQR >30%. RESULTS: The mean liver stiffness in inactive HBsAg carriers was 5.6+/-2.1kPa, significantly higher than in normal subjects (4.8 +/- 1.2 kPa, p = 0.0002). In 16.4% (23) of inactive carriers, liver stiffness exceeded 7 kPa (the cutoff for significant fibrosis F >= 2). In patients with undetectable viral loads, the mean liver stiffness was 4.9 +/- 1.2 kPa, significantly lower than in those with detectable DNA (< 2000 IU/ml) (6.7 +/- 2.7 kPa, p < 0.001). CONCLUSIONS: Inactive HBsAg carriers have higher liver stiffness values compared with healthy individuals. Liver stiffness in inactive HBsAg carriers with detectable viral loads is higher than in those who are aviremic, suggesting that low viral loads promote fibrosis. PMID- 22087141 TI - Percutaneous exposure incidents in nurses: Knowledge, practice and exposure to hepatitis B infection: Percutaneous exposure incidents in nurses. AB - BACKGROUND: Nurses are at risk of percutaneous exposure incidents (PEIs), which may lead to serious or even fatal blood-borne infections. OBJECTIVES: To determine the prevalence of PEIs in the last year, among nurses and to assess their knowledge about and frequency of safe method of practice in exposure to blood-borne pathogens (especially, to HBV). MATERIALS AND METHODS: A cross sectional study in 2008 was conducted on 138 nurses working in general surgery and obstetrics/gynecology services of Qazvin University of Medical Sciences, Qazvin, Central Iran. A questionnaire for assessment of risk factors for contracting HBV infection was completed by nurses. RESULTS: Overall, the prevalence of needle stick injury (NSI) and direct exposure to body fluids were 52.9% (95% CI: 44.5%-61.3%) and 65.4% (95% CI: 57.4% - 73.8%), respectively. There was no statistically significant difference between the two studied centers in terms of sharp injuries; however, the rate of repeated NSI (number per each year >=3) and mucocutaneous exposures were significantly higher in the general surgery ward. The overall coverage of vaccination in the two studied centers was 96.3%, but the rate of accurate answers to many questions pertaining to knowledge and practice were less than 50%. CONCLUSIONS: Nurses are still at significant risk for developing NSI and mucocutaneous exposure. Continuous educational programs (especially by highlighting the seriousness of the problem) are necessary for improving this situation because inadequate education might increase unsafely practice. PMID- 22087142 TI - Epidemiological features of patients infected with HCV genotype 4 in Poland: Epidemiology of HCV genotype 4 in Poland. AB - BACKGROUND: Hepatitis C genotype 4 (HCV-4) is considered to be rare outside northern Africa and southern Europe. OBJECTIVES: To describe the epidemiological characteristics of patients infected with HCV-4 in Poland. PATIENTS AND METHODS: The study group included 290 patients with HCV-related chronic liver disease and intravenous drug users with HCV infection recruited in years 2002-2006 in Podlaskie region, north-eastern Poland. In all cases, HCV infection was confirmed by HCV-RNA detection by qualitative nested RT-PCR. HCV genotype was determined by 5'UTR sequencing and comparison with known genotype-specific sequences. RESULTS: HCV 4 was found in 45 (15.5%) of 290 HCV-infected and HCV RNA-positive individuals. 60% of HCV 4 infections occurred in intravenous drug users; 51% of HCV 4-infected patients were also HIV-positive. Among 119 patients whose source of infection was other than drug use, there were 16 (10.5%) HCV 4 cases. Seven (46%) of 13 HCV 4-positive and HIV-negative patients who received combined antiviral treatment had sustained viral response. CONCLUSIONS: HCV 4 exists in eastern Poland, and the infection is frequently related to intravenous drug use and accompanied by HIV infection. HCV 4 also causes a proportion of non-drug related HCV infections. PMID- 22087143 TI - Clinical values of AFP, GPC3 mRNA in peripheral blood for prediction of hepatocellular carcinoma recurrence following OLT: AFP, GPC3 mRNA for prediction of HCC. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Annually, about 200,000 patients died of HCC in China. Liver transplantation (LT) holds great theoretical appeal in treating HCC. However, the high recurrence rate after transplantation is the most important limiting factor for long-term survival. OBJECTIVES: To assess the value of alpha-fetoprotein (AFP) messenger RNA (mRNA), Glypican-3 (GPC3) mRNA-expressing cells in the peripheral blood (PB) for prediction of HCC recurrence following orthotopic liver transplantation (OLT). PATIENTS AND METHODS: 29 patients with HCC who underwent OLT with a minimum clinical follow-up of 12 months were included in this retrospective study. We detected AFP mRNA, GPC3 mRNA-expressing cells in the PB by TaqMan real-time reverse transcriptase-polymerase chain reaction (RT-PCR), pre , intra- and post-operatively. The early recurrence of patients was evaluated. RESULTS: 8 (28%), 15 (52%), and 9 (31%) patients had AFP mRNA detected pre-, intra-, and post-operatively, respectively. With 12 months of follow-up, HCC recurred in 7 (24%) patients. Univariate analysis revealed that positive pre- and post-operative AFP mRNA, TNM stage as well as vascular invasion were significant predictors for the HCC recurrence. Multivariate analysis revealed that being positive for AFP mRNA pre-operatively remained a significant risk factor for HCC recurrence after OLT. GPC3 mRNA was expressed in all PB samples. There was no significant difference in the expression levels of GPC3 mRNA between the HCC and control groups. There were no significant differences in GPC3 mRNA expression values between those patients with and without tumor recurrence. CONCLUSIONS: The pre-operative detection of circulating AFP mRNA-expressing cells could be a useful predictor for HCC recurrence following OLT. GPC3 mRNA-expressing cells in PB seem to have no diagnostic value. PMID- 22087144 TI - Seroprevalence of hepatitis B virus among hemodialysis patients in Bushehr province, southern Iran: HBV seroprevalence in hemodialysis patients. AB - BACKGROUND: Hepatitis B virus (HBV) infection is still reported from adult hemodialysis units. OBJECTIVES: To determine the prevalence of anti-HBs antibody in hemodialysis patients and the correlation between levels of anti-HBs antibody with other factors. PATIENTS AND METHODS: HBsAg, anti-HBs and anti-HBc antibodies level in 119 hemodialysis patients were evaluated by enzyme-linked immunosorbent assay. RESULTS: Seroconversion (anti-HBs antibody >10 IU/L) was found in 22 patients. Minimum protective antibody level was found in patients aged >=60 years. Statistically significant correlation was not found between anti-HBs antibody and gender. Ten (8.4%) patients had abnormal ALT and/or AST. Prevalence of HBsAg, anti-HBc antibody, HBeAg and anti-HBe antibody were found in 8 (6.72%), 24 (25.16%), 2 (1.68%) and 3 (2.52%) patients, respectively. CONCLUSIONS: Periodic assessment of anti-HBs antibody level is strongly recommended in patients undergoing hemodialysis. PMID- 22087145 TI - Primary hepatic diffuse large B cell lymphoma: A case report: Primary hepatic diffuse large B cell lymphoma. AB - In this report we describe a rare case of primary hepatic diffuse large B cell lymphoma in a 67-year-old man who presented with abdominal pain, deteriorated liver function, elevated lactate dehydrogenase. He was found to have diffuse nodular intrahepatic space-occupying lesion with normal alpha-fetoprotein and carcino-embryogenic antigen. The final diagnosis was made by percutaneous biopsy of the liver as the clinical manifestation not consistent with common liver diseases. The patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) without surgical resection with a favorable response. However, serious complication was occurred after 4 cycles of chemotherapy, and the patient finally died of concurrent acute respiratory distress syndrome. PMID- 22087146 TI - Pernicious anemia in case of chronic viral hepatitis infection: Pernicious anemia and chronic viral hepatitis. PMID- 22087147 TI - When calculation of minimum sample size is not justified: When sample size calculation is not justified. PMID- 22087148 TI - Hydroxyurea: A useful adjunct to the standard antiviral therapy in chronic hepatitis B. PMID- 22087149 TI - Hepatitis A virus infection: Is it an important hazard to public health?: hazards of HAV for public health. PMID- 22087150 TI - The optimal dose of ribavirin for chronic hepatitis C: From literature evidence to clinical practice: The optimal dose of ribavirin for chronic hepatitis C. AB - Approximately 170 million people worldwide are chronically infected by hepatitis C virus (HCV), which can result in progressive hepatic injury and fibrosis, culminating in cirrhosis and end-stage liver disease. The benchmark therapy for untreated HCV patients is a combination of pegylated interferon-alpha (PEG-IFN) and ribavirin (RBV). Several studies have suggested several potential new approaches to improve HCV therapy-optimization of the dose and duration of RBV therapy, accompanied by careful clinical management, is crucial in ensuring the greatest likelihood of a long response to therapy. RBV causes serious side effects, but in clinical practice, there are no alternatives for the treatment of HCV infection. Based on our results, weight-based doses of RBV are advantageous for genotype 1-infected patients, but its success in genotype 2- and 3-infected patients is unknown, particularly for shorter treatment durations. PMID- 22087151 TI - The impact of Hepatitis C virus infection on kidney transplantation outcomes: A systematic review of 18 observational studies: The impact of HCV on renal transplantation. AB - BACKGROUND: Hepatitis C virus (HCV) infection occursin 0% to 51% of dialysis patients, and manyHCV-positive patients are urged to undergo kidney transplantation. However, the outcome of renal transplantation in HCV-positive recipients is unknown. OBJECTIVES: Our review aimed to address the outcomesof renal transplantation recipients (RTRs)following kidney transplantation. MATERIALS AND METHODS: We selected studies that used the adjusted relative risk (aRR) and 95% CI of all-cause mortality and graft loss in HCV-positive compared with HCV-negative RTRs as study endpoints. Cox proportional hazard analysis was usedin all studies to calculate the independent effects of HCV infection on RTR outcomes. Sixteen retrospective cohort studies and 2 clinical trials were selected for our review. Sixteen studies were related to patient survival, and 12 examined graft survival. RESULTS: The combined hazard ratio in HCV-infected recipients was 1.69-fold (1.33-1.97, p < 0.0001) and 1.56 times (1.22-2.004, p < 0.0001) greaterthan that of HCV-negative recipients for mortality and graft loss, respectively. CONCLUSIONS: Although HCV-infected RTRs have worseoutcomes than HCV negative RTRs,kidney transplantation is the preferred treatment for patients with HCV infection and end-stage renal disease. PMID- 22087152 TI - Risk factors of hepatitis B virus infection in Turkey: A population-based, case control study: Risk Factors for HBV Infection. AB - BACKGROUND: Although the World Health Organization (WHO) classifies Turkey as a country with a moderate-high prevalence of hepatitis B virus (HBV) infection, there is little data on HBV transmission in this country. OBJECTIVES: To identify risk factors for HBV infection, we performed a retrospective case-control study between January 2007 and December 2009. PATIENTS AND METHODS: Acute HBV patients and population controls were selected, and data from these groups were analyzed by logistic regression method. RESULTS: The study included 129 patients with acute HBV infection and 219 controls. Hemodialysis (OR:8.2, 95% CI: 4.17-16.61, p < 0.05), having an HBsAg (+) spouse (OR: 4.3, 95% CI:2.17-8.53, p < 0.05), living with an HBsAg (+) parent(s) (OR: 3.25, 95% CI:1.73-6.12, p < 0.05), and being male (OR: 1.34, 95% CI: 0.82-2.21, p < 0.05) were independent risk factors that were potentially associated with HBV infection. More than one-third of female patients had a significantly higher risk (34.5% vs. 13.5%, p < 0.05) of acquiring HBV from their sexual partners. Hemodialysis was the most frequent risk factor (46.9% vs. 20%, x (2) = 10.45, p < 0.05) for patients aged over 31 years, and living with HBsAg (+) parents was a significantly higher risk factor (28.8% vs. 10.2%, x (2) = 6.15, p < 0.05) that is more likely to lead to HBVin patients aged under 30 years. CONCLUSIONS: This study suggests that persons in Turkey who undergo hemodialysis are at high risk for acquiring HBV. Having an HBsAg (+) spouse (sexual transmission) or living with HBsAg (+) parents (household transmission) are significant risk factors for HBV transmission. Vaccination appears to be better preventive method against the spread of HBV. PMID- 22087153 TI - Hepatitis B seromarkers, hepatitis C antibody, and risk behaviors in married couples, a bordered province of western Thailand: Hepatitis B seromarkers, hepatitis C antibody, and risk behaviors. AB - BACKGROUND: Married couples constitute a target group for reducing the risk of infections with hepatitis B virus (HBV) and hepatitis C virus (HCV). OBJECTIVES: This study attempted to assess HBV seromarkers, anti-HCV-positive rates, and risk behaviors among married couples in a bordered province of western Thailand. MATERIALS AND METHODS: A cross-sectional study of 114 married couples aged 15-44 years was performed. Approximately 25-30 married couples were randomly selected from 4 districts in a province of western Thailand. All study participants who participated voluntarily were interviewed using structured questionnaires. Their blood specimens were collected to screen for HBV seromarkers (HBsAg, anti-HBs, and anti-HBc) and anti-HCV. RESULTS: Approximately 21.1% of husbands and 2.6% of wives had a history of extramarital sex without using a condom; 18.4% of husbands and 4.4% of wives had tattoos; and 18.4% and 3.5%, respectively, consumed alcohol regularly. Additionally, 4.4% of husbands and 2.6% of wives had a history of sexual contact before marriage. In the serological study, 10.5% of husbands and 5.3% of wives were HBsAg-positive, and 1.8% of husbands and 0.9% of wives were anti-HCV-positive. Among HBsAg-positive subjects, 15/18 had spouses who were positive for any HBV marker, and 1 had a spouse who was HBsAg- and anti-HBc positive. Three participants were positive for anti-HCV (2 males and 1 female). One anti-HCV-positive male had a history of regular alcohol consumption and extramarital sex without a condom, and another had a history of intravenous drug use. The anti-HCV-positive female had a history of sexual contact before marriage. CONCLUSIONS: This study found high percentages of risk behaviors and HBsAg positivity among married couples in a bordered province of western Thailand, especially in husbands. These findings support the evidence of HCV transmission via sexual contact and intravenous drug use. PMID- 22087154 TI - Platelet count/bipolar spleen diameter ratio for the prediction of esophageal varices: The special Egyptian situation: Noninvasive prediction of esophageal varices. AB - BACKGROUND: Esophageal variceal hemorrhage is a devastating complication of portal hypertension that occurs in approximately one-third of cirrhotic patients. OBJECTIVES: We assessed the value of the platelet count/ bipolar spleen diameter ratio as a noninvasive parameter for the prediction of esophageal varices (EVs) in Egyptian cirrhotic patients. PATIENTS AND METHODS: Laboratory and ultrasonographic and imaging variables were prospectively evaluated in 175 patients with liver cirrhosis. All patients underwent upper gastrointestinal endoscopy. Patients with active gastrointestinal bleeding at the time of admission were excluded. RESULTS: The platelet count/ bipolar spleen diameter ratio in patients with EVs was significantly lower than in patients without EVs. In an analysis of the receiver operating characteristic curves (ROCs), we calculated an optimal cutoff value of 939.7 for this ratio, which gave 100% sensitivity and negative predictive values, 86.3% specificity, a 95.6% positive predictive value, and an area under the ROC curve of 0.94 +/- 0.02, reflecting its overall diagnostic accuracy. These findings were extended to a subset analysis of compensated cirrhotic patients. CONCLUSIONS: The platelet count/ bipolar spleen diameter ratio has excellent accuracy in the noninvasive assessment of EVs in patients with compensated or decompensated liver cirrhosis. It is easy to calculate and can lower the financial and sanitary burdens of endoscopy units, especially in developing countries. PMID- 22087155 TI - Commentary on: A study of genotype, mutants and nucleotide sequence of HBV in Pakistan: Genotype, mutants, and nucleotide sequence of HBV. PMID- 22087156 TI - New potential instrument to fight hepatocellular cancer by restoring p53. PMID- 22087158 TI - Correlation between HBsAg quantitative assay results and HBV DNA levels in chronic HBV. AB - BACKGROUND: Viral load has been used to diagnose and monitor patients who are being treated for chronic hepatitis B (CHB). The Diagnosis methods are molecular based and expensive. Quantitation of hepatitis B surface antigen (HBsAg) by automated chemiluminescent micro-particle immunoassay has been proposed to be a surrogate marker. Quantitating HBV DNA levels molecularly is expensive; thus, a cheaper laboratory test as a surrogate diagnostic marker might simplify our management. OBJECTIVES: We determined whether quantitative HBsAg levels correlate with HBV DNA levels in CHB. PATIENTS AND METHODS: In this cross-sectional study, all CHB patients who were referred by a gastroenterologist to undergo quantitative HBV DNA assay in a qualified laboratory in Mashhad, Iran in 2009 were enrolled, and blood samples was obtained. Patients who were positive for antibodies to HCV and HDV were excluded. HBV DNA was measured by real-time polymerase chain reaction, and serum HBsAg was quantified byelectrochemiluminescence assay (Roche Diagnostic). RESULTS: Of 97 patients, 70 were male (72%) and 27 were female (28%); the mean age was 39 +/- 11 years. Eighty-seven percent wasHBeAg-negative. By Mann-Whitney test,HBSAg titer differed significantly between HBeAg-positive and -negative patients (P = 0.001), as did HBV DNA levels (P = 0.009). By Spearman test, there was no significant correlation between HBsAg and HBV DNA levels (P= 0.606 and r = 0.53). CONCLUSIONS: HBeAg-negative patients have higher levels of HBsAg and lower levels of HBV DNA. By electrochemiluminescence assay,HBsAg has no significant correlation with HBV DNA levels in CHB with predominant genotype D and HBeAg negativity in Iran. PMID- 22087157 TI - Liver complications in celiac disease. AB - Celiac disease (CD) is characterized by sensitivity to gluten, which is found in dietary wheat, barley, and rye. Many extra-intestinal manifestations have been described in association with CD. Liver disease and CD share widespread risk factors. Liver disorders such as autoimmune hepatitis, elevation of liver enzyme levels, primary biliary cirrhosis, nonspecific hepatitis, primary sclerosing cholangitis, and nonalcoholic fatty liver disease have been reported in patients with CD. In this review, we provide information regarding liver disorders that may be found in association with celiac disease and the effect of the treatment of CD on these disorders. PMID- 22087159 TI - The prevalence of hepatitis B antigen-positivity in the general population of Mashhad, Iran. AB - BACKGROUND: Hepatitis B virus (HBV) infection is a significant health problem throughout the world. OBJECTIVES: We aimed to evaluate the prevalence of hepatitis B antigen (HBsAg) seropositivity in the general population of Mashhad, northeast of Iran. PATIENTS AND METHODS: One thousand six hundred fifty-two healthy individuals aged 1 to 90 (Mean; 29.1 +/- 18.5) from all 12 municipalities of Mashad were selected randomly by multistage cluster sampling. Informed consent was obtained, and demographics and medical histories were collected. Twice reactive samples were considered HBsAg-positive by ELISA. Chi-square test and logistic regression were applied to analyze the factors related to HBsAg positivity using SPSS 16.0. RESULTS: The overall prevalence of HBsAg positivity was 1.39% (95% CI, 0.91% to 2.12%); 2.0% and 0.89% among men and women, respectively (p = 0.054). Infection was more prevalent in older (p = 0.019) and married persons (p = 0.001), Afghanis (p = 0.046), and those with a history of traditional cupping (p = 0.005). There was no association between HBV infection and gender; literacy; income; employment; family size; or history of blood transfusion, dental procedure, surgery, hospitalization, or tattooing. By logistic regression analysis, age was the only variable that had a significant association with infection (p = 0.026). CONCLUSION: It seems that the prevalence of HBV infection in Mashhad is slightly lower than that of the nation. PMID- 22087160 TI - The HBV DNA cutoff value for discriminating patients with HBeAgnegative chronic hepatitis B from inactive carriers. AB - BACKGROUND: Patients with HBeAg-negative chronic hepatitis B (CHB) has a significantly different prognosis than inactive carriers; there is however, no reliable strategy for accurately differentiating these two disease conditions. OBJECTIVES: To determine a strategy for discriminating patients with HBeAg negative CHB from inactive carriers. MATERIALS AND METHODS: Consecutive inactive carriers (i.e. HBeAg-negativity, anti-HBe-positivity, normal ALT levels, and HBV DNA < 2000 IU/mL) were enrolled. HBV reactivation was defined as the elevation of the HBV DNA level to >= 2000 IU/mL. Patients were classified into true inactive carriers when their HBV DNA levels remained at < 2000 IU/mL or false inactive carriers when their HBV DNA levels increased to >= 2000 IU/mL during the first year. RESULTS: The Mean +/- SD age of 208 inactive carriers (140 males) was 47.7 +/- 12.6 years. The Mean +/- SD serum ALT and HBV DNA levels were 22.8 +/- 8.6 IU/L and 360 +/- 482 IU/mL, respectively. HBV reactivation developed in 41 (19.7%) patients during the first year. Baseline HBV DNA and ALT levels differed significantly between true inactive and false inactive carriers. The AUROCs of the baseline ALT and HBV DNA levels for predicting a false inactive carrier were 0.609 and 0.831, respectively. HBV reactivation developed more often in patients with a baseline HBV DNA level of >= 200 IU/mL than in those with a baseline HBV DNA level of < 200 IU/mL during a Mean +/- SD follow-up of 622 +/- 199 days. CONCLUSIONS: The HBV DNA level was useful for discriminating patients with HBeAg negative CHB from true inactive carriers. The follow-up strategies applied to inactive carriers need to vary with their HBV DNA levels. PMID- 22087161 TI - The optimal threshold: Baseline serum hepatitis B virus DNA and alanine transaminase levels can predict the 2-Year on-treatment virological response to lamivudine. AB - BACKGROUND: HBV is still a worldwide health problem. Annually about 0.5-1.2 million patients die of HBV-related diseases such as liver cirrhosis and hepatocellular carcinoma. Lamivudine (LAM) is the first nucleoside analog used in the treatment of chronic hepatitis B. As LAM has been clinically used for a long time, increasing clinical experience has been achieved showing that the resistance mutation rate is relatively high. Numerous studies have also focused on the predictive factors of long-term efficacy of LAM treatment. OBJECTIVES: To determine the optimal cutoff values of baseline hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels as predictors for the long-term efficacy of LAM treatment in patients with chronic hepatitis B. PATIENTS AND METHODS: A total of 163 HBeAg-positive chronic hepatitis B patients receiving LAM treatment were recruited into the present study. Logistic regression analysis was performed to find out the independent predictors of 2-year on-treatment virological response among the baseline parameters. The receiver operating characteristic (ROC) curve was used to evaluate the optimal cutoff values of these independent predictors. The accuracy of the prediction was assessed using the area under curve (AUC) and optimal cutoff values were determined through maximizing the Youden's index. RESULTS: After 2 years of LAM treatment, undetectable HBV DNA was maintained in 114 (69.9%) patients. LAM-related resistance mutation (YMDD mutation) was detected in 45 (27.6%) patients. Logistic regression analysis indicated that the baseline ALT and HBV DNA levels were the independent predictors of the efficacy. ROC curve analysis suggested the integration parameter derived from the baseline ALT and HBV DNA levels had the maximal predictive value for a 2-year on-treatment virological response. The optimal cutoff values of ALT and HBV DNA were 220 IU/L and 8.2 log10 copies/mL, respectively. CONCLUSIONS: The incidence of LAM resistant mutations in HBeAg-positive chronic hepatitis B patients may be significantly reduced and long-term efficacy improved when the baseline ALT was greater than 220 IU/L and HBV DNA was less than 8.2 log10 copies/mL. PMID- 22087162 TI - The effect of desacetyluvaricin on the expression of TLR4 and P53 protein in Hepg 2.2.15. AB - BACKGROUND: Previous studies suggest that annonaceous may cause permeability glycoprotein (P-gp) function to abate, leading to cell apoptosis. It has also been reported that annonaceous acetogenins affect hepatocellular carcinoma (HCC) cells in the G1 phase, leading to apoptosis. Desacetyluvaricin (Des), a new type of annonaceous acetogenin monomer, has a significant effect on HCC, with few side effects. OBJECTIVES: To investigate the effect of Des on the expression of Toll like receptor 4 (TLR4) and P53 protein in HCC. MATERIALS AND METHODS: HCC HepG2.2.15 cell was cultured by routine method. HepG2.2.15 cells were divided into three groups: control group, treated with Des and DDP (cisplatin) which were examined by immunofluorescence flow cytometry for expression of TLR4 and P53. RESULTS: TLR4 was expressed by more cells in the Des group than in the cisplatin or serum-only groups (71.94%, 42.64%, and 37.16%, respectively; Des vs.cisplatin: p < 0.05; Des vs. serum only: p < 0.05), with no difference between the cisplatin and serum-only groups (p > 0.05). P53 was expressed by more cells in the Des and cisplatin groups than in the serum-only group (32.6%, 31.5% and 3.3%, respectively; Des vs. serum only, p < 0.05; cisplatin vs. serum only, p < 0.05), with no difference between the Des and cisplatin groups (p > 0.05). CONCLUSIONS: Des increases TLR4 and P53 expression in HCC cells. Improved immune recognition by the former effect and induction of apoptosis by the latter could be the mechanisms of Des's clinical effects on HCC. PMID- 22087163 TI - Hepatitis B and C among women with illegal social behavior in Isfahan, Iran: Seroprevalence and associated factors. AB - BACKGROUND: In Iran, there is limited evidence on the prevalence of hepatitis B and C viruses (HBV and HCV) among females who engage in illegal sexual behavior. OBJECTIVES: To determine the prevalence of HBV and HCV infections and their associated factors in this population in Isfahan-Iran. PATIENTS AND METHODS: In this cross-sectional study, 100 females who engaged in illegal sexual behavior during 2009-2010 in Isfahan were recruited from welfare to the DIC for women, and referrals were made among those who knew others who engaged in prostitution. Markers for HBV and HCV-Ab were measured by ELISA, and recombinant immunoblot assay was used for confirmation of HCV infection. Also, a questionnaire on demographics and prostitution-associated risk data in a face-to-face interview was completed for each participant. Chi-square and multivariate logistic regression models were used for data analysis. RESULTS: Of the 100 samples collected, 91 were sufficient for testing. The mean age and time spent in sex work were 30.84 +/- 9.34 years and 36 +/- 28.5 months, respectively. HBsAg was detected in 1 (1.1%), anti-HBc in 4 (4.4%), anti-HBs in 60 (65.9%), and HCV Ab in 9 (9.9%) subjects. The evidence of vaccination was seen in 54 subjects (59.3%). There were no significant differences in the prevalence of HBV or HCV infection by estimated risk factors, and there was no independent risk factor for these infections. CONCLUSIONS: The high prevalence of HCV infection in this study indicates the need to implement preventive interventions for female sex workers and, perhaps more importantly, to involve their male clients. PMID- 22087165 TI - Commentary on: Aspartate transaminase to platelet ratio index (APRI): A simple noninvasive index assessing liver fibrosis in patients with chronic liver diseases. PMID- 22087164 TI - Increased liver stiffness in extrahepatic cholestasis caused by choledocholithiasis. AB - BACKGROUND: Extrahepatic cholestasis that is caused by benign and malignant diseases has been reported to increase liver stiffness (LS), as measured by transient elastography (TE). OBJECTIVES: The aim of this study was to evaluate LS in patients with extrahepatic cholestasis due to choledocholithiasis before and after endoscopic sphincterotomy and stone removal. PATIENTS AND METHODS: LS was measured by TE (Fibroscan) in patients with extrahepatic cholestasis that was caused by choledocholithiasis before and 1 month after endoscopic sphincterotomy and successful stone removal. RESULTS: We studied 12 patients (7 females, 5 males), aged 36 to 76 years (mean age 57.1 +/- 11.6 years), with extrahepatic cholestasis that was caused by choledocholithiasis. LS was increased in all patients (range: 6.2-18.4 kPa; mean: 8.9 +/- 3.5 kPa) before endoscopic therapy. Successful biliary drainage was effected by sphincterotomy and stone removal in all patients, which led to a significant decline in LS to 3.9-8.1 kPa (Mean: 5.6 +/- 1.2 kPa; p < 0.001) within a mean observation time of 29 days. The decrease in LS values correlated significantly with a decline in serum total bilirubin levels (r = 0.691; p < 0.0001). CONCLUSIONS: Extrahepatic cholestasis due to choledocholithiasis increases LS and should be excluded before assesing liver fibrosis by transient elastography. PMID- 22087166 TI - Commentary on: Noninvasive assessment of liver fibrosis using aspartate transaminase to platelet ratio index (APRI) in adult patients with chronic liver disease. PMID- 22087167 TI - Is the aspartate transaminase to platelet ratio index adequate for the assessment of liver fibrosis in patients with chronic liver disease? PMID- 22087168 TI - Liver fibrosis in patients with chronic liver diseases: are laboratory tests useful to diagnosis? PMID- 22087169 TI - Rosuvastatin and chronic hepatitis C. PMID- 22087170 TI - IL28B SNP genotyping among Iranian HCV-infected patients: A preliminary report. PMID- 22087171 TI - The necessity of booster vaccination after neonatal hepatitis B vaccination. PMID- 22087172 TI - Blood safety concerns in the Eastern Mediterranean region. AB - Blood transfusion is a life-saving component of health care systems. Nevertheless, it can also be a quick and easy method of exposing patients to risks, particularly the transmission of infectious agents to recipients. Despite substantial improvements in the safety of transfusion services worldwide, the presence of paid and replacement blood donors are still of cause concern for ensuring sustainable safe blood donations. Although the Eastern Mediterranean region consists of a heterogeneous group of countries that vary in their levels of development, they all share common concerns regarding blood safety. In the region, concerns regarding the spread of Hepatitis B and C through blood transfusion continue to exist. Therefore, there is an urgent need for further improvements in both organization and safety measures of blood transfusion activities in the region. Although establishing a centralized blood transfusion system might not be achievable in the short term in some of the countries in the region, the implementation of centralized test kit procurement, data collection, and donation testing could be considered feasible approaches. PMID- 22087173 TI - Role of living donor liver transplantation in the treatment of hepatitis C virus infection. AB - Hepatitis C virus (HCV) infection is one of the most common indications for liver transplantation worldwide. Because of the existing organ shortage, adult-to-adult living donor liver transplantation (LDLT) has become an important method of expanding the donor pool to meet the ever-increasing need. However, despite advantages such as the quality of the hepatic graft and the timing of the transplant, the exact role of LDLT in the treatment of HCV is still unclear. In this review, we aim to address some of these issues in an effort to highlight both the advantages and disadvantages, as well as to identify the main challenges, of using LDLT for treating patients with HCV infection. PMID- 22087174 TI - Cytogenetic methods for detection of oxidative stress and evaluation of antioxidant therapy in hepatitis C infection. AB - The plasma of patients with hepatitis C contains chromosome-damaging substances, the so-called "clastogenic factors" (CFs), as this is the case for other chronic inflammatory diseases and after radiation exposure. These endogenous clastogens, formed as a consequence of increased superoxide production by inflammatory cells, can be detected with cytogenetic methods, as they are used for exogenous clastogens. The long-lived, autosustained DNA-damaging effects of CFs are risk factors for the development of cancer and leukemia. In hepatitis C, the highest clastogenic scores has been observed in patients with hepatocellular carcinoma. In agreement with the link to inflammation, clastogenic score are correlated with necro-inflammatory scores in liver biopsies. Antioxidant therapy with a powerful superoxide scavenger resulted in normalization of clastogenic scores and significant decreases in aminotransferase levels, but did not influence the virus load. Preliminary results of our study on a limited number of patients suggest that pre-treatment with antioxidants may improve the outcome of interferon/ribavirin treatment. A comparison of a three-month treatment with either interferon alone or the antioxidant alone, yielded similar results for reduction of ALT levels, but only complete normalization of clastogenic scores for the antioxidant. Further studies have to be conducted to see whether a combination of an antiviral agent with an appropriate antioxidant would allow to reduce interferon and its side effects.Combination of antioxidants with IFN/RIBA was also reported by other authors with discordant results. The CF-test can be useful in clinical trials for the choice of the appropriate antioxidant. PMID- 22087175 TI - Should a booster dose be administered in children after mass immunization for hepatitis B? AB - BACKGROUND: Hepatitis B virus infection is a global health problem and vaccine preventable disease, but the duration of the effects of HBV vaccination in infants is unknown. OBJECTIVES: The aim of this trial, which comprised children who had received 3 doses as part of the universal HBV immunization program and no additional doses, was to investigate anti-HBs titers and HBsAg status after 9 years. PATIENTS AND METHODS: We performed a descriptive, cross-sectional field research study. The study sample, based on sociodemographics and minimum seroprevalence, was analyzed based on 10.00% +/- 1.50 (95% confidence interval) (1150 individuals); trial was realized in a total of 1279 children (623 females and 656 males). Anti-HBs titers were measured by micro-EIA (Dia Sorin-Italy); titers < 10 IU/mL were negative, 10-49 IU/mL were low-positive, and > 50 IU/mL were high-positive. For anti-HBs titers below protective levels, HBsAg was measured by micro-EIA. RESULTS: In approximately half of the children (48.5% in those living in semiurban areas and 42.3% in urban areas), antibody titers were below protective levels. CONCLUSIONS: Mass HBV vaccination, which was implemented in Turkey in 1998, significantly decreases HBsAg positivity in childhood. Nevertheless, it might be necessary to administer a booster dose after 8-9 years in children, especially those in low socioeconomic areas or in whom irregular/insufficient immunization is suspected. PMID- 22087176 TI - Protective effect of intermittent clamping of the portal triad in the rat liver on liver ischemia-reperfusion injury. AB - BACKGROUND: Intermittent clamping (IC) of the portal triad is an effective method of protecting the liver from ischemia-reperfusion injury (IR). In clinical practice, this method is employed during a resection, but its mechanism is still not clear. OBJECTIVES: To evaluate the effect of IC on rat liver and determine its mechanisms. MATERIALS AND METHODS: Wistar rats were submitted to 60-min IC (cycles of 12-min clamping followed by 4-min reperfusion), and the samples were collected after 1, 6, and 72 hrs of reperfusion. We determined the serum activity of alanine aminotransferase (ALT), and measured the concentration of TNF-alpha, malondialdehyde (MDA) and myeloperoxidase (MPO) in liver homogenates. The apoptosis of hepatocytes was evaluated immunohistochemically. RESULTS: When compared to the IR rats, the activity of ALT decreased in the IC group in all periods of observation (the highest decrease of ~48% after 1 hr of reperfusion). When compared to the IR group, a statistically significant decrease (p < 0.05) in the TNF-alpha concentration (~33%) in the IC rats occurred only after 1 hr of reperfusion, and it was accompanied by a decrease in the MPO concentration after 1 and 6 hrs of reperfusion. IC reduces the effects of reactive oxygen species (ROS) activity, which has been confirmed by a statistically significant decrease in MDA concentration by 25%-35% in all studied periods. The limitation of hepatocytes apoptosis due to IC occurs in the early (~26%; p < 0.05) and late (~45%; p < 0.01) phases of reperfusion. CONCLUSIONS: The use of IC in early phase of reperfusion brings about a decrease in TNF-alpha release, which can be related to liver injury due to neutrophil infiltration and apoptotic cell reduction. It seems that the reduction of lipid peroxidation may also limit the liver injury. PMID- 22087177 TI - Non-alcoholic fatty liver disease and correlation of serum alanin aminotransferase level with histopathologic findings. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been recognized as the most common cause of chronic liver disease worldwide. It occurs in patients who do not consume alcohol in large amounts. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) are indicators of hepatocellular injury. OBJECTIVES: To determine correlation between histopathologic specifications of NAFLD in patients with little or no history of alcohol consumption and the serum level of ALT. PATIENTS AND METHODS: In a cross-sectional study carried out in two gastroenterology and hepatology clinics in Tehran, Iran, the medical records of those who had undergone liver biopsies between years 2005 and 2009 were reviewed. Clinical and laboratory information of biopsy-proven cases of NAFLD were obtained from 147 eligible medical records. The histopathologic, demographic, and laboratory data of the participants were also collected. Two groups of patients according to their serum ALT level (cut-point of 35 U/L) were defined. The quantitative pathologic grade of the biopsy specimens was determined based on Brunt scoring system. RESULTS: We studied 147 NAFLD patients including 127 men (86.4%) and 20 women (13.6%) with a mean +/- SD age of 41.4 +/- 11.2 years. Considering serum ALT, the mean +/- SD quantitative grade of hepatosteatosis was 1.50 +/- 0.67 and 1.74 +/- 0.73 (p=0.136); advanced fibrosis (consisted of grade III and cirrhosis) was found in 4.5% (1/22) and 5.6% (7/125) of patients (p=0.327). CONCLUSIONS: We found that using the cut-off value of 35 U/L for serum ALT level, it has little contribution to predict NAFLD severity. PMID- 22087178 TI - Prevalence of hepatitis E virus and porcine caliciviruses in pig farms of Guizhou province, China. AB - BACKGROUND: Hepatitis E virus (HEV) and caliciviruses are enteric pathogens of humans and animals, and pigs have been considered an important reservoir of these viruses. OBJECTIVES: The aim of this study is to determine the infection rates of HEV and caliciviruses (sapovirus [SaV] and norovirus [NoV]) in different age groups of pigs in Guizhou province, China, and characterize the strains that are prevalent in this mountainous area. MATERIALS AND METHODS: A total of 209 stool samples from healthy pigs of different ages were collected from 6 pig farms in Guizhou province from May to June 2009 and tested for HEV, SaV, and NoV by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: The overall prevalence of porcine HEV and porcine SaV was 6.7% (15/209) and 1.0% (2/209), respectively. No NoV was detected. The prevalence rates of porcine HEV infection were 15.4% in piglets aged < 1 mon (4/26), 6.8% in piglets aged between 1 and 4 mon (3/44), 12.5% in piglets aged ~ 4 mon (6/48), and 1.1% in sows aged between 6 and 14 mon (2/91). Porcine SaV was detected only in piglets (7.7%, 2/26). All 10 HEV isolates belonged to genotype 4, clustering with a human HEV strain (AF103940) from an adjacent province. CONCLUSIONS: This is the first report on the existence of porcine SaV in swine in Guizhou province, China. The clustering of the porcine HEV isolates with a human strain suggests cross-species transmission between swine and humans in this area. PMID- 22087179 TI - The effects of milk thistle on hepatic fibrosis due to methotrexate in rat. AB - BACKGROUND: Extracts of milk thistle (MT), Silybum marianum, have been used as medical remedies since the time of ancient Greece. Methotrexate is a potentially hepatotxic drug. OBJECTIVES: To clarify the hepatoprotective effects of MT on methotrexate. MATERIALS AND METHODS: From January 2010 to April 2010, 30 male rats were recruited into three 10-rat subgroups in Tabriz University of Medical Sciences. Normal saline was injected intraperitoneally in the first group (A; the controls); intraperitoneal methotrexate plus oral MT extract were administered to the second group (B) and intraperitoneal methotrexate alone was given to the third group (C). Pre- and post-interventional measuring of serum parameters were carried out every 15 days. After six weeks, the rats were decapitated and histopathological evaluation of liver was done. RESULTS: Serum liver enzymes (AST, ALT), alkaline phosphatase, total and direct bilirubin, creatinine and BUN were measured on days 0, 15, 30, 45. They were significantly higher in the group C, comparing with other two groups. Serum albumin was the least in group C animals as well. There were no significant differences between groups A and B. The mean+/-SD fibrosis score using semi-quantitative scoring system (SSS) was 1.25+/-0.46, 1.40+/-0.52 and 6.70+/-0.82, in groups A, B and C, respectively (p<0.001). CONCLUSIONS: MT extract can effectively prevent methotrexate-induced liver dysfunction and fibrosis in rats. PMID- 22087180 TI - Association of interleukin 18 gene promoter polymorphisms with HBV recurrence after liver transplantation in Han Chinese population. AB - BACKGROUND: There is growing evidence suggesting that interleukin-18 (IL-18) plays a crucial role in viral clearance and disease pathogenesis, and that single nucleotide polymorphisms (SNPs) within the gene may influence its production. OBJECTIVES: To investigate the potential association of two polymorphisms ( 137G/C and 607C/A) in the promoter region of the IL-18 gene with the risk of HBV recurrence after liver transplantation (LT) in Han Chinese patients. PATIENTS AND METHODS: IL-18 promoter genotyping was performed by the snapshot technique in 125 patients with HBV-related end-stage liver disease (ESLD) receiving LT in our center from 2004 to 2008. RESULTS: Among the study samples, no significant association between the IL-18 promoter polymorphisms ( 137G/C and 607C/A) or haplotypes and HBV recurrence after LT was found. CONCLUSIONS: The polymorphisms ( 137G/C and 607C/A) in the promoter region of the IL-18 gene may not play a key role in HBV recurrence after LT in Han Chinese population, and may not be suitable predictors for HBV recurrence in clinical practice. PMID- 22087181 TI - Occult hepatitis B: Evolving challenges and new perspectives. PMID- 22087182 TI - Broader use of hepatitis B virus vaccine: Efficacy in those who lost hepatitis B surface antigen during follow-up. PMID- 22087183 TI - Aspartate transaminase to platelet ratio index (APRI) to assess liver fibrosis in patients with chronic liver disease. PMID- 22087184 TI - Immune response to hepatitis B vaccine in patients who lost hepatitis B surface antigen during follow up. PMID- 22087185 TI - Do we need a common liver fibrosis index or etiology-related indices? PMID- 22087186 TI - Advances of interventional radiology in treatment of hepatobiliary diseases in Iran. AB - Interventional radiologists are physicians who specialize in minimally invasive targeted therapies, offering the most in-depth knowledge of the less invasive therapies that are available and diagnostic and clinical experience across all specialties. Interventional radiologists offer treatments for hepatobiliary diseases without significant side effects or damage to the adjacent normal tissue. We briefly introduce some of the interventional procedures in gastroenterology. PMID- 22087187 TI - Halothane: Is there still any place for using the gas as an anesthetic? AB - The fluorinated hydrocarbons that are used for anesthesia are derived from ether. Although they have many benefits, there are several side effects of these drugs, including untoward hepatic effects. Whether the use of halothane gas can be revitalized is unknown. Introducing nanocarriers inside the halothane molecule can increase its benefits as an anesthetic in the lungs and cardiovascular system and prevent exposure to the liver. The findings of new fields, such as cancer therapy, and anesthetic agents, such as propofol, can improve the quality of the drug using nanomedicine. PMID- 22087189 TI - Use of duplex mutation primers for real-time PCR quantification of hepatitis C virus RNA in serum. AB - BACKGROUND: The duplex mutation primers offer many advantages over other multi labeled probes for real-time detection of amplification products. OBJECTIVES: To develop and validate a novel real-time PCR for quantification of HCV RNA based on the duplex mutation primers technology. MATERIALS AND METHODS: The duplex mutation primers were selected in the highly conservative 5' non-coding region (5'NCR) of the HCV RNA. The assay was validated with the Viral Quality Control panel, which also includes Chinese HCV RNA standards. RESULTS: The detection limit was 57 IU/mL, and a good linear correlation in the range of 102-108 IU/mL was revealed (r(2) = 0.999) with the novel method. This assay has a dynamic range of at least 8 log10 without the need for specimen dilution, good clinical intra- and inter-run precision, and excellent correlation with a commercially available assay(r(2) = 0.95). CONCLUSIONS: The high sensitivity, wide linear range, and good reproducibility, combined with low cost, make this novel quantitative HCV real-time PCR assay particularly well suited for application to clinical and epidemiological studies. PMID- 22087188 TI - Barriers to receiving hepatitis C treatment for people who inject drugs: Myths and evidence. AB - BACKGROUND: Alcohol consumption, current injecting drug use, and pre-existing mental illness have been identified as 3 of the main reasons for excluding patients from treatment for hepatitis C. OBJECTIVES: We reviewed the literature to obtain an evidence base for these common exclusion criteria. MATERIALS AND METHODS: We reviewed original research and meta-analyses investigating the effects of alcohol consumption, current injecting drug use, and pre-existing mental illness. RESULTS: We identified 66 study reports relevant to the review, but found only limited evidence to support withholding of treatment on the basis of the 3 previously mentioned exclusion criteria. CONCLUSIONS: Currently, there is a lack of evidence for many of the barriers faced by patients in availing treatment for hepatitis C. Adherence to treat routine was found to be a better predictor of sustained virological response than injecting drug or alcohol consumption during treatment period or the presence of a pre-existing mental disorder. Although several challenges remain, we need to ensure that treatment decisions are based on the best available evidence and the treatment is performed appropriately on a case-by-case basis. PMID- 22087191 TI - Viral hepatitis as an occupational disease in Poland. AB - BACKGROUND: In medical terms, occupational diseases are defined as health disorders specifically associated with the working environment of people and their occupational activity. From the medical and legal perspectives, the vast majority of European countries consider particular diseases to be of occupational origin if they are mentioned in the current list of occupational diseases and caused by exposure to factors in the working environment that are harmful to health. OBJECTIVES: The aim of this study was to analyze the occurrence of cases of viral hepatitis certified as an occupational disease in Poland during 1979 2009. This article presents the medical, economic, and legal aspects of the epidemiology of hepatitis as an occupational disease in Poland. MATERIALS AND METHODS: Publically available statistical data on certified occupational diseases in Poland and data contained in individual "occupational disease diagnosis cards" (based on data used in Poland statistical form), regarding certified cases of hepatitis among health care professionals, which were collected by the Department of Occupational Hygiene of the Polish Public Health Service, were analyzed in this study. RESULTS: In Poland, the highest number of cases of hepatitis certified as an occupational disease was observed in 1987. A gradual reduction in the number of cases of hepatitis as an occupational disease has been noted since then. Currently, hepatitis C as an occupational disease is certified more frequently than hepatitis B. In Poland, the number of women with hepatitis certified as an occupational disease is higher than that of men. However, among health care professionals, particularly nurses, this difference is insignificant because women outnumber the men. The existence of such a situation is due to the significant quantitative predominance of women over men among medical personnel, especially among nurses. CONCLUSIONS: Immunization of health care professionals against the hepatitis B virus (HBV), introduced in Poland in 1988, was an important factor involved in reducing the number of cases of occupational viral hepatitis. Socioeconomic and financial factors affected the epidemiological data on cases of hepatitis certified as an occupational disease in Poland. An additional problem associated with the diagnosis of occupational diseases is the lack of obligatory testing for anti-hepatitis C virus (HCV) and anti-hepatitis B surface antigen (HBsAg) antibodies and examinations to ensure the efficacy of HBV vaccination among medical staff before and during employment. PMID- 22087190 TI - How efficient is acoustic radiation force impulse elastography for the evaluation of liver stiffness? AB - BACKGROUND: In chronic liver diseases, a correct estimation of the severity of liver fibrosis is important for recommendations regarding the treatment. Nowadays, evaluation of fibrosis is done by noninvasive methods such as biochemical scores and transient elastography instead of liver biopsy. The lack of sensitivity to detect fibrosis, because of its heterogeneity is a drawback of liver biopsy (LB). OBJECTIVES: To compare transient elastography (TE) and acoustic radiation force impulse (ARFI) for the evaluation of liver stiffness (LS), against percutaneous LB. PATIENTS AND METHODS: Our study comprised of 223 subjects; 52 without fibrosis (38 volunteers and 14 patients with F0 on LB), 36 with F1, 40 with F2, 26 with F3 and 69 with liver cirrhosis (46 with LB and 23 with signs of cirrhosis). For each patient we performed in the same session 10 TE and 5 ARFI measurements. The median values were calculated. RESULTS: A strong linear correlation (Spearman rho = 0.870) was found between TE and fibrosis (P < 0.0001); there was also a weaker correlation between ARFI and fibrosis (Spearman rho = 0.646; P < 0.0001). TE measurements were also correlated with ARFI measurements (Spearman rho = 0.733, P < 0.0001). The best test for predicting significant fibrosis (F >= 2) was TE with a cut-off value of 7.1 kPa (AUROC 0.953). For ARFI, the cut-off value was 1.27 m/s-area under ROC curve (AUROC): 0.890, sensitivity (Se) of 88.7%, specificity (Sp) of 67.5%, positive predictive value (PPV) of 64.5%, and negative predictive value (NPV) of 90% (P = 0.0044). For predicting cirrhosis (F = 4), the optimum cut-off values were 14.4 kPa for TE (AUROC: 0.985, Se: 95.6%, Sp: 94.7%, PPV: 89.2%, NPV: 98%) and 1.7 m/s for ARFI (AUROC: 0.931, Se: 93%, Sp: 86.7%, PPV: 73.6%, NPV: 96.9%) (P = 0.0102). CONCLUSIONS: LS evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis. ARFI is an accurate test for the diagnosis of cirrhosis. PMID- 22087192 TI - Use of artificial neural network to predict esophageal varices in patients with HBV related cirrhosis. AB - BACKGROUND: Prediction of esophageal varices in cirrhotic patients by noninvasive methods is still unsatisfactory. OBJECTIVES: To evaluate the accuracy of an artificial neural network (ANN) in predicting varices in patients with HBV related cirrhosis. PATIENTS AND METHODS: An ANN was constructed with data taken from 197 patients with HBV related cirrhosis. The candidates for input nodes of the ANN were assessed by univariate analysis and sensitivity analysis. Five-fold cross validation was performed to avoid over-fitting. RESULTS: 14 variables were reduced by univariate and sensitivity analysis, and an ANN was developed with three variables (platelet count, spleen width and portal vein diameter). With a cutoff value of 0.5. The ANN model has a sensitivity of 96.5%, specificity of 60.4%, positive predictive value of 86.9%, negative predictive value of 86.5% and a diagnostic accuracy of 86.8% for the prediction of varices. CONCLUSIONS: An ANN may be useful for predicting presence of esophageal varices in patients with HBV related cirrhosis. PMID- 22087194 TI - Indirect markers of fibrosis in chronic liver diseases: Is aspartate transaminase to-platelet ratio (APRI) a useful test? PMID- 22087193 TI - A new scoring system for prediction of fibrosis in chronic hepatitis C. AB - BACKGROUND: Liver biopsy (LB) is still considered to be the gold standard for assessment of liver fibrosis. OBJECTIVES: To evaluate the effectiveness of various non-invasive methods for predicting liver fibrosis, including transient elastography (TE), APRI score, Lok score, Forns score, FIB-4 score, Fibrosis Index, King score, and Bonacini score, in comparison with the effectiveness of LB and to create a new scoring system for fibrosis prediction. PATIENTS AND METHODS: This study included 212 patients with chronic HCV hepatitis. LB, TE, and various biological tests were performed during a single hospital visit. Using established formulae, data from these tests were used to create scores for assessment of liver fibrosis. RESULTS: The results of all the tests showed significant correlation with histological fibrosis. TE results (r = 0.62), King score (r = 0.57), and APRI score (r = 0.56) showed the closest correlation with severity of fibrosis. The following formula was derived from our data by multiple regression: Predicted liver fibrosis score (PLF score) = 0.956 + 0.084 * TE - 0.004 * King score + 0.124 * Forns score + 0.202 * APRI score. A direct correlation (r = 0.68) was found between the PLF score and liver fibrosis. The cut-off values of the PLF score for various stages of fibrosis were: F >= 1, 1.77 (Area under ROC curve (AUROC) = 0.76); F >= 2, 2.18 (AUROC = 0.78); F >= 3, 2.47 (AUROC = 0.86); and F = 4, 2.98 (AUROC = 0.97). CONCLUSIONS: We found that our newly developed PLF score, which is derived from the scores of multiple tests, is more strongly correlated with fibrosis than each component score used individually. The PLF score is more effective than TE for predicting severe fibrosis, but they have similar effectiveness in predicting liver cirrhosis. PMID- 22087195 TI - Aspartate aminotransferase to platelet ratio index for the assessment of liver fibrosis severity in patients with chronic hepatitis. PMID- 22087196 TI - Noninvasive assessment of liver fibrosis with aspartate transaminase to platelet ratio index (APRI). PMID- 22087197 TI - Treatment of steroid-resistant pediatric nephrotic syndrome. AB - Children who suffer from steroid-resistant nephrotic syndrome (SRNS) require aggressive treatment to achieve remission. When intravenous high-dose methylprednisolone fails, calcineurin inhibitors, such as cyclosporine and tacrolimus, are used as the first line of treatment. A significant number of patients with SRNS progress to end-stage renal disease if remission is not achieved. For these children, renal replacement therapy can also be problematic; peritoneal dialysis may be accompanied by significant protein loss through the peritoneal membrane, and kidney allograft transplantation may be complicated by recurrence of SRNS. Plasmapheresis and rituximab were initially used for treatment of recurrent SRNS after transplantation; these are now under consideration as rescue therapies for refractory SRNS. Although the prognosis of SRNS is complicated and unfavorable, intensive treatment in the early stages of the disease may achieve remission in more than half of the patients. Therefore, timely referral of pediatric SRNS patients to pediatric nephrology specialists for histological and genetic diagnosis and treatment is highly recommended. PMID- 22087198 TI - Complications of nephrotic syndrome. AB - Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. Renal histology reveals the presence of minimal change nephrotic syndrome (MCNS) in more than 80% of these patients. Most patients with MCNS have favorable outcomes without complications. However, a few of these children have lesions of focal segmental glomerulosclerosis, suffer from severe and prolonged proteinuria, and are at high risk for complications. Complications of NS are divided into two categories: disease-associated and drug-related complications. Disease-associated complications include infections (e.g., peritonitis, sepsis, cellulitis, and chicken pox), thromboembolism (e.g., venous thromboembolism and pulmonary embolism), hypovolemic crisis (e.g., abdominal pain, tachycardia, and hypotension), cardiovascular problems (e.g., hyperlipidemia), acute renal failure, anemia, and others (e.g., hypothyroidism, hypocalcemia, bone disease, and intussusception). The main pathomechanism of disease-associated complications originates from the large loss of plasma proteins in the urine of nephrotic children. The majority of children with MCNS who respond to treatment with corticosteroids or cytotoxic agents have smaller and milder complications than those with steroid-resistant NS. Corticosteroids, alkylating agents, cyclosporin A, and mycophenolate mofetil have often been used to treat NS, and these drugs have treatment-related complications. Early detection and appropriate treatment of these complications will improve outcomes for patients with NS. PMID- 22087199 TI - Clinical characteristics and outcomes among pediatric patients hospitalized with pandemic influenza A/H1N1 2009 infection. AB - PURPOSE: The purpose of this article is to describe the clinical and epidemiologic features and outcomes among children hospitalized with pandemic influenza A/H1N1 2009 infection. METHODS: We retrospectively reviewed the charts of hospitalized pediatric patients (<18 years) diagnosed with pandemic influenza A/H1N1 2009 infection by reverse-transcriptase polymerase chain reaction at a tertiary hospital in Seoul, Korea, between September 2009 and February 2010. RESULTS: A total of 72 children were hospitalized with pandemic influenza A/H1N1 2009 infection (median age, 6.0 years; range, 2 months to 18 years). A total of 40% had at least 1 underlying medical condition, including asthma (17%), malignancies (19%), and heart diseases (17%). Of the 72 patients, 54 (76%) children admitted with H1N1 infection showed radiographic alterations compatible with pneumonia. There was no significant difference in pre-existing conditions between pandemic influenza A/H1N1 infected patients with or without pneumonia. Children with pandemic influenza A/H1N1 pneumonia were more likely to have a lower lymphocyte ratio (P=0.02), higher platelet count (P=0.02), and higher level of serum glucose (P=0.003), and more commonly presented with dyspnea than did those without pneumonia (P=0.04). CONCLUSION: No significant differences in age, sex, or presence of preexisting conditions were found between children hospitalized with pandemic influenza A/H1N1 H1N1 influenza infection with pneumonia and those without pneumonia. Higher leukocyte count, higher glucose level, and a lower lymphocyte ratio were associated with the development of pandemic A/H1N1 2009 influenza pneumonia. PMID- 22087200 TI - Polymorphisms of methylenetetrahydrofolate reductase are not a risk factor for Kawasaki disease in the Korean population. AB - PURPOSE: Hyperhomocysteinemia is known as a risk factor for atherosclerosis. Preclinical arteriosclerosis is noted and premature atherosclerosis is known to be accelerated in Kawasaki disease (KD) patients. Genetic polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene result in elevated plasma homocysteine concentrations and are known to be associated with the development of coronary artery disease. Our hypothesis is that single nucleotide polymorphisms (SNPs) of the MTHFR gene are related to the development of KD and coronary artery lesions (CALs). METHODS: For this study, we selected 3 candidate single nucleotide polymorphisms (SNPs) (rs2274976, rs1801131, and rs1801133) of MTHFR. These SNPs are located on chromosome 1p36.3. We included 101 KD patients and 306 healthy adults as controls in this study. CALs were seen in 38 patients. Genotypes of the selected SNPs were determined by direct sequencing and analyzed with SNPAlyze. RESULTS: The genetic distribution and allelic frequency of the 3 MTHFR SNPs (rs2274976, rs1801131, and rs1801133) were not significantly different in patients with KD compared to the control group (P=0.71, 0.17, and 0.96, respectively). There was no difference in the genetic distribution of the MTHFR SNPs between the normal control group and the CAL group (P=0.43, 0.39, 0.52 respectively). CONCLUSION: The genetic distribution of the MTHFR SNPs (rs2274976, rs1801131, and rs1801133) was not different in the KD group compared to the control group. In addition, the genetic distribution of these SNPs was not different in the CAL group compared to the control group in the Korean population. PMID- 22087201 TI - Log-transformed plasma level of brain natriuretic peptide during the acute phase of Kawasaki disease is quantitatively associated with myocardial dysfunction. AB - PURPOSE: Brain natriuretic peptide (BNP) has been considered a biochemical marker for myocarditis in Kawasaki disease. We performed this study to determine its quantitative significance. METHODS: We attempted to correlate log-transformed BNP concentrations (log-BNP) and clinical, laboratory, and echocardiographic variables in 81 children with Kawasaki disease. Stepwise multiple linear regression analysis was used to determine the variables independently associated with log-BNP concentration. RESULTS: Serum C-reactive protein level (P<0.0001), serum alanine aminotransferase concentration (P=0.0032), white blood cell count (P=0.0030), and left ventricular mass index (P=0.0024) were positively related with log-BNP, and hemoglobin level (P<0.0001), serum albumin level (P<0.0001), Na(+) concentrations (P<0.0001), left ventricular fractional shortening (P=0.0080), and peak early diastolic tissue velocity of the left ventricular basal lateral segment (P=0.0045) were negatively related to the log-BNP concentration. Multiple regression analysis showed that serum albumin concentration (R(2)=0.31, P=0.0098) and left ventricular mass index (R(2)=0.09, P=0.0004) were significantly associated with the log-BNP concentration. CONCLUSION: Elevated BNP levels during the acute phase of Kawasaki disease may be attributable to cardiac dysfunction associated with the increase in left ventricular mass, and log-BNP concentration may be a quantitative biochemical marker of myocarditis in Kawasaki disease. PMID- 22087202 TI - 2009 H1N1 influenza virus infection and necrotizing pneumonia treated with extracorporeal membrane oxygenation. AB - A 3-year-old girl with acute respiratory distress syndrome due to a H1N1 2009 influenza virus infection was complicated by necrotizing pneumonia was successfully treated with extracorporeal membrane oxygenation (ECMO). This is the first reported case in which a pediatric patient was rescued with ECMO during the H1N1 influenza epidemic in Korea in 2009. PMID- 22087203 TI - Masticator space abscess in a 47-day-old infant. AB - A 47-day-old male infant presented with fever, poor oral intake, irritability, and right-sided bluish buccal swelling. Contrast-enhanced computed tomography of the neck showed a round mass lesion of about 2.0*1.5 cm that suggested abscess formation in the right masticator space. Ultrasound-guided extraoral aspiration of the abscess at the right masseter muscle was successful. Staphylococcus aureus was identified in the culture from the aspirated pus and blood. Appropriate antibiotics were given and the patient recovered. The patient underwent follow-up ultrasonography that showed an improved state of the previously observed right masseter muscle swelling at about 1 month after hospital discharge. A masticator space abscess usually originates from an odontogenic infection in adults. We report a case of masticator space abscess in a 47-day-old infant in whom septicemia without odontogenic infection was suspected. PMID- 22087204 TI - Disability-adjusted life years analysis: implications for stroke research. AB - Stroke is a prototype disorder that disables as well as kills people. The disability-adjusted life years (DALY) metric developed by the World Health Organization to measure the global burden of disease integrates healthy life years lost due to both premature mortality and living with disability. Accordingly, it is well suited to stroke research. The DALY has previously been applied only to large but relatively crude population-level data analyses, but now it is possible to calculate the DALY lost in individual stroke patients. Measuring each patient's stroke outcome with DALY lost has expanded its application to the analysis of treatment effect in acute stroke trials, delineating the poststroke complication impact, the differential weighting of discrete vascular events, and estimating a more refined stroke burden in a specific population. The DALY metric has several advantages over conventional stroke outcome measures: 1) Since the DALY measures the burden of diverse health conditions with a common metric of life years lost, stroke burden and benefits of stroke interventions can be directly compared to other health conditions and their treatments. 2) Quantifying stroke burden or interventional benefits as the life years lost or gained makes the DALY metric more intuitively accessible for public and health system planners. 3) As a continuous, equal-interval scale, the DALY analysis might be statistically more powerful than either binary or ordinal rank outcome analyses in detecting the treatment effects of clinical trials. 4) While currently employed stroke outcome measures take one-time snapshots of disability or mortality and implicitly indicate long-term health impact, the DALY explicitly indicates the burdens of living with disability for an individual's remaining life. PMID- 22087206 TI - Psychiatric symptoms and quality of life in patients with drug-refractory epilepsy receiving adjunctive levetiracetam therapy. AB - BACKGROUND AND PURPOSE: Levetiracetam (LEV) is a new antiepileptic drug that has been found to be effective as an adjunctive therapy for uncontrolled partial seizures. However, the results of several studies suggested that LEV has negative psychotropic effects, including irritability, aggressiveness, suicidality, and mood disorders. We investigated the impact of adjunctive LEV on psychiatric symptoms and quality of life (QOL) in patients with drug-refractory epilepsy (DRE) and determined the risk factors provoking psychiatric adverse events. METHODS: A 24-week, prospective, open-label study was conducted. At enrollment, we interviewed patients and reviewed their medical charts to collect demographic and clinical information. They were asked to complete self-report health questionnaires designed to measure various psychiatric symptoms and QOL at enrollment and 24 weeks later. RESULTS: Seventy-one patients were included in the study, 12 patients (16.9%) of whom discontinued LEV therapy due to serious adverse events including suicidality. The risk factor for premature withdrawal was a previous history of psychiatric diseases (odds ratio 4.59; 95% confidence interval, 1.22-17.32). LEV intake resulted in significant improvements in Beck Anxiety Inventory score (p<0.01) and some domains of the Symptom Checklist-90 Revised, such as somatization (p<0.05), obsessive-compulsiveness (p<0.05), depression (p<0.05), and anxiety (p<0.05). These improvements were not related to the occurrence of seizure freedom. The Quality of Life in Epilepsy Inventory-31 overall score and subscale scores, such as seizure worry (p<0.01), overall QOL (p<0.05), emotional well-being (p<0.05), energy-fatigue (p<0.05), and social function (p<0.05), also improved. CONCLUSIONS: Adjunctive LEV in patients with DRE is likely to improve psychiatric symptoms and QOL. Clinicians should be well aware of the psychiatric histories of patients to prevent them from developing serious adverse events related to LEV. PMID- 22087205 TI - New insights into neuromyelitis optica. AB - Neuromyelitis optica (NMO) is an idiopathic inflammatory disorder of the central nervous system (CNS) that preferentially affects the optic nerves and spinal cord. In Asia, NMO has long been considered a subtype of multiple sclerosis (MS). However, recent clinical, pathological, immunological, and imaging studies have suggested that NMO is distinct from MS. This reconsideration of NMO was initially prompted by the discovery of a specific antibody for NMO (NMO-IgG) in 2004. NMO IgG is an autoantibody that targets aquaporin-4 (AQP4), the most abundant water channel in the CNS; hence, it was named anti-AQP4 antibody. Since it demonstrated reasonable sensitivity and high specificity, anti-AQP4 antibody was incorporated into new diagnostic criteria for NMO.The spectrum of NMO is now known to be wider than was previously recognized and includes a proportion of patients with recurrent, isolated, longitudinally extensive myelitis or optic neuritis, and longitudinally extensive myelitis or optic neuritis associated with systemic autoimmune disease or with brain lesions typical of NMO. In this context, a new concept of "NMO spectrum disorders" was recently introduced. Furthermore, seropositivity for NMO-IgG predicts future relapses and is recognized as a prognostic marker for NMO spectrum disorders. Humoral immune mechanisms, including the activation of B-cells and the complement pathway, are considered to play important roles in NMO pathogenesis. This notion is supported by recent studies showing the potential pathogenic role of NMO-IgG as an initiator of NMO lesions. However, a demonstration of the involvement of NMO-IgG by the development of active immunization and passive transfer in animal models is still needed. This review focuses on the new concepts of NMO based on its pathophysiology and clinical characteristics. Potential management strategies for NMO in light of its pathomechanism are also discussed. PMID- 22087207 TI - Efficacy and safety of switching from oral cholinesterase inhibitors to the rivastigmine transdermal patch in patients with probable Alzheimer's disease. AB - BACKGROUND AND PURPOSE: The goal of this study was to estimate the efficacy and safety of the rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD) who cannot tolerate or do not respond to oral cholinesterase inhibitors (ChEIs). METHODS: A 24-week, prospective, open-label, single-arm, multicenter study was conducted from June 2009 to June 2010 in patients with probable AD. The enrolled patients had either a poor response or a decline in global function after treatment with oral ChEIs, or they were not able to tolerate treatment with oral ChEIs due to adverse events such as nausea or vomiting. A poor response was defined as a decrease of at least 2 points on the Korean version of the Mini-Mental State Examination (K-MMSE) within the previous 6 months (the decline in global function was determined by the investigator or caregiver). The efficacy of treatment was assessed using a follow-up Clinical Global Impression of Change (CGIC) assessment and K-MMSE conducted after 24 weeks, and safety was measured by the occurrence of adverse events and patient disposition. RESULTS: In total, 164 patients aged 74.7+/-7.52 years (mean+/-SD) and with 5.12+/-3.64 years of education were included. The study was completed by 70% of the patients (n=116), with 12.2% discontinuing due to adverse events. The most frequently reported adverse events (11%) were skin lesions, such as erythema or itching, followed by gastrointestinal problems (1.2%). Either an improvement or no decline in CGIC scores was reported for 82% of the patients. CONCLUSIONS: The immediate switching of patients from an oral ChEI to the rivastigmine transdermal patch without a washout period was safe and well tolerated by the probable-AD patients in this study. PMID- 22087208 TI - Polymorphism of the Glutamate Transporter Protein EAAT2 and Migraine Transformation into Chronic Daily Headache. AB - BACKGROUND AND PURPOSE: The progression of migraine into chronic daily headache involves multiple risk factors, but the main contributor is not known. Glutamate is the major excitatory neurotransmitter in central sensitization, which is an important process in the pathogenesis of migraine transformation. The glutamate transporter protein excitatory amino acid transporter 2 (EAAT2) is the primary modulator of glutamatergic neurotransmission, and genetic polymorphisms of its gene, EEAT2, have been identified. The aim of this study was to determine the effect of EAAT2 polymorphisms on migraine transformation into chronic daily headache. METHODS: We included 74 migraine patients with episodic attack (M-E) and 59 migraine patients with chronic daily headache (M-CDH). After amplifying EAAT2 by polymerase chain reaction, we assessed its genotype frequencies based on restriction fragment length polymorphisms. We reclassified all migraine patients into two groups according to their EAAT2 genotype, either with the A allele (n=62) or without it (n=71), and compared the clinical variables between the two groups. RESULTS: The genotype frequencies of EAAT2 polymorphisms did not differ between the M-E and M-CDH groups. Comparison between EEAT2 genotypes revealed that the frequency of analgesic usage was significantly higher among migraine patients with the A allele (12.9+/-1.6 days/month) than in those without the A allele (8.1+/-1.2 days/month; p=0.019). The other clinical variables of migraine did not differ between the two groups. CONCLUSIONS: The results suggest that EEAT2 polymorphism contributes to the tendency toward frequent analgesic usage in migraine patients. This implies a potential genetic influence on the progression of migraine into chronic daily headache through the development of medication overuse headache. PMID- 22087209 TI - Changes in Length of Stay for Neurological Geriatric Diseases in Korea between 2003 and 2007. AB - BACKGROUND AND PURPOSE: The elderly population and the prevalence of stroke, dementia, and Parkinson's disease are increasing rapidly in Korea. The aim of this study was to establish the length of stay (LOS) for neurological geriatric diseases, and analyze this parameteraccording to healthcare institutions. METHODS: We used data from the Health Insurance Review and Assessment Service from 2003 to 2007. Nineteen neurological geriatric diseases were classified into four groups: dementia, cerebral hemorrhage, cerebral infarction, and Parkinson's disease. LOS was analyzed according to gender, age, insurance type, disease group, and type of healthcare institution. RESULTS: The LOS for neurological geriatric diseases lengthened from 5,550,193 days (10.8% of the total National Health Insurance admission days) in 2003 to 14,749,671 days (19.7%) in 2007. The mean LOS was 40.8 days in 2003, and lengthened to 71.2 days in 2007. After stratification by disease group, the mean LOS for long-term-care hospitals lengthened by 1.43 times (from 81.7 to 116.6 days) in the cerebral infarction group, 1.35 times (from 85.6 to 115.2 days) in the cerebral hemorrhage group, and 1.28 times (from 82.7 to 105.7 days) in the Parkinson's disease group. CONCLUSIONS: The LOS for neurological geriatric diseases has lengthened markedly, which isdue to an increasesin the number of hospitalized patients and the mean LOS, which have increased most rapidly in long-term-care hospitals. These results may be useful in developing geriatric health policies. PMID- 22087210 TI - Ipsilateral tilt and contralateral sensory change of neck in cortical infarction. AB - BACKGROUND: Numerous neck muscles are involved in neck movements, and so isolated neck weakness is extremely uncommon in cerebral infarction. CASE REPORT: We report herein the case of a 65-year-old woman with hypertension and acute cortical infarction, presenting with ipsilateral head tilt and contralateral sensory changes in the neck and shoulder area, which has never been described before. CONCLUSIONS: Transient neck weakness and sensory deficits can occur in acute cortical infarction. The motor representation of the neck muscles can be at the same level of the cortical sensory representation, near to the level of the trunk representation, which is in contrast to Penfield's findings. Several possible mechanisms for the ipsilateral tilt are described. PMID- 22087211 TI - Emergency microsurgical embolectomy for the treatment of acute intracranial artery occlusion: report of two cases. AB - BACKGROUND: The main treatment for acute arterial ischemic stroke is intravenous or intra-arterial thrombolysis within a particular time window. Endovascular mechanical embolectomy is another treatment option in the case of major artery occlusion. Endovascular mechanical embolectomy is a useful technique for restoring blood flow in patients with large-vessel occlusion, and especially in those who are contraindicated for thrombolytics or in whom thrombolytic therapy has failed. CASE REPORT: We report herein two cases of emergency microsurgical embolectomy for the treatment of acute middle cerebral artery and internal carotid artery occlusion as an alternative treatment for major artery occlusion. CONCLUSIONS: Emergency microsurgical mechanical embolectomy may be an alternative treatment option for restoring blood flow in selected patients with large-vessel acute ischemic stroke. PMID- 22087212 TI - Spontaneous Carotid Cavernous Fistula in a Case with Protein S Deficiency that Newly Developed Ophthalmoplegia after Embolization. AB - BACKGROUND: Carotid cavernous fistula (CCF) is an abnormal communication between the carotid artery and the cavernous sinus. The pathogenesis of spontaneous CCF remains unclear, although sinus thrombosis is known to be a predisposing factor for dural arteriovenous fistula. Because spontaneous CCFs are mainly of the dural type, we considered that thrombogenic conditions, such as, protein S deficiency might be associated with CCF. CASE REPORT: A 42-year-old woman complained of conjunctival injection and retro-orbital pain that first appeared 1-month before visiting our hospital. She had no history of head trauma or intracranial surgery. Exophthalmos and chemosis were observed in her left eye, which also had lower visual acuity and higher intraocular pressure than the right eye. Magnetic resonance images and cerebral angiography revealed a left dural CCF. Her protein S was low, at 41% (normal range: 70-140%), but other hematologic values related to coagulation were normal. Her symptoms were relieved after initial transvenous coil embolization. However, a newly developed sixth-nerve palsy was detected 4 days after initial embolization. Follow-up angiography revealed a minimal shunt, and thus transvenous coil embolization was repeated. Two days later, the ophthalmoplegia started reducing, and 1-month later it had almost disappeared. CONCLUSIONS: To the best of our knowledge, this is the first report of spontaneous dural CCF in a Korean patient with concurrent protein S deficiency. Interestingly, transient sixth-nerve palsy developed after transvenous coil embolization in this patient. This additional symptom caused by the residual fistula was relieved after additional transarterial embolization. PMID- 22087213 TI - Concurrence of Multifocal Motor Neuropathy and Hashimoto's Thyroiditis. AB - BACKGROUND: Multifocal motor neuropathy (MMN) is an immune-mediated disorder that is characterized by slowly progressive and asymmetrical weakness, but its pathophysiological mechanism is uncertain. The hypothesis that MMN is an immunological disease has been supported by the proven therapeutic effects of intravenous immunoglobulin and the detection of antiganglioside antibodies in MMN patients. The coexistence of MMN with other immune diseases has been rarely reported. CASE REPORT: A 37-year-old woman visited our hospital complaining of weakness in both hands. The clinical manifestations coincided well with MMN: predominantly distal upper-limb weakness, asymmetric involvement, a progressive course, absence of sensory symptoms, absence of pyramidal signs, and sparing of the cranial muscles. The electrophysiological findings also supported a diagnosis of MMN, with motor nerve conduction block in the median, ulnar, and radial nerves, without sensory nerve involvement. The patient was simultaneously diagnosed as having Hashimoto's thyroiditis, which is a well-known immune mediated disease. CONCLUSIONS: The concurrence of MMN and Hashimoto's thyroiditis in our patient is significant for understanding the immunological characteristics of the two diseases. PMID- 22087215 TI - Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate. AB - AIMS/HYPOTHESIS: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet) Colesevelam HCl (BAS) for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13)C]-glucose, [2-(13)C]-glycerol, [1-(2)H] galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001), a ~300% increased glucokinase flux (p = 0.001) and a ~200% increased total hepatic glucose production rate (p = 0.0002). BAS treatment increased glucose metabolic clearance rate by ~37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317) but not in liver (p = 0.189). Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030) and 3-fold in db/db mice (p = 0.002). CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content. PMID- 22087216 TI - EGFR-targeted hybrid plasmonic magnetic nanoparticles synergistically induce autophagy and apoptosis in non-small cell lung cancer cells. AB - BACKGROUND: The epidermal growth factor receptor (EGFR) is overexpressed in 80% of non-small cell lung cancer (NSCLC) and is associated with poor survival. In recent years, EGFR-targeted inhibitors have been tested in the clinic for NSCLC. Despite the emergence of novel therapeutics and their application in cancer therapy, the overall survival rate of lung cancer patients remains 15%. To develop more effective therapies for lung cancer we have combined the anti-EGFR antibody (Clone 225) as a molecular therapeutic with hybrid plasmonic magnetic nanoparticles (NP) and tested on non-small cell lung cancer (NSCLC) cells. METHODOLOGY/PRINCIPAL FINDINGS: Cell viability was determined by trypan-blue assay. Cellular protein expression was determined by Western blotting. C225-NPs were detected by electron microscopy and confocal microscopy, and EGFR expression using immunocytochemistry. C225-NP exhibited a strong and selective antitumor effect on EGFR-expressing NSCLC cells by inhibiting EGFR-mediated signal transduction and induced autophagy and apoptosis in tumor cells. Optical images showed specificity of interactions between C225-NP and EGFR-expressing NSCLC cells. No binding of C225-NP was observed for EGFR-null NSCLC cells. C225-NP exhibited higher efficiency in induction of cell killing in comparison with the same amount of free C225 antibody in tumor cells with different levels of EGFR expression. Furthermore, in contrast to C225-NP, free C225 antibody did not induce autophagy in cells. However, the therapeutic efficacy of C225-NP gradually approached the level of free antibodies as the amount of C225 antibody conjugated per nanoparticle was decreased. Finally, attaching C225 to NP was important for producing the enhanced tumor cell killing as addition of mixture of free C225 and NP did not demonstrate the same degree of cell killing activity. CONCLUSIONS/SIGNIFICANCE: We demonstrated for the first time the molecular mechanism of C225-NP induced cytotoxic effects in lung cancer cells that are not characteristic for free molecular therapeutics thus increasing efficacy of therapy against NSCLC. PMID- 22087217 TI - Incentive or habit learning in amphibians? AB - Toads (Rhinella arenarum) received training with a novel incentive procedure involving access to solutions of different NaCl concentrations. In Experiment 1, instrumental behavior and weight variation data confirmed that such solutions yield incentive values ranging from appetitive (deionized water, DW, leading to weight gain), to neutral (300 mM slightly hypertonic solution, leading to no net weight gain or loss), and aversive (800 mM highly hypertonic solution leading to weight loss). In Experiment 2, a downshift from DW to a 300 mM solution or an upshift from a 300 mM solution to DW led to a gradual adjustment in instrumental behavior. In Experiment 3, extinction was similar after acquisition with access to only DW or with a random mixture of DW and 300 mM. In Experiment 4, a downshift from DW to 225, 212, or 200 mM solutions led again to gradual adjustments. These findings add to a growing body of comparative evidence suggesting that amphibians adjust to incentive shifts on the basis of habit formation and reorganization. PMID- 22087218 TI - Population status of a cryptic top predator: an island-wide assessment of tigers in Sumatran rainforests. AB - Large carnivores living in tropical rainforests are under immense pressure from the rapid conversion of their habitat. In response, millions of dollars are spent on conserving these species. However, the cost-effectiveness of such investments is poorly understood and this is largely because the requisite population estimates are difficult to achieve at appropriate spatial scales for these secretive species. Here, we apply a robust detection/non-detection sampling technique to produce the first reliable population metric (occupancy) for a critically endangered large carnivore; the Sumatran tiger (Panthera tigris sumatrae). From 2007-2009, seven landscapes were surveyed through 13,511 km of transects in 394 grid cells (17*17 km). Tiger sign was detected in 206 cells, producing a naive estimate of 0.52. However, after controlling for an unequal detection probability (where p = 0.13+/-0.017; +/-S.E.), the estimated tiger occupancy was 0.72+/-0.048. Whilst the Sumatra-wide survey results gives cause for optimism, a significant negative correlation between occupancy and recent deforestation was found. For example, the Northern Riau landscape had an average deforestation rate of 9.8%/yr and by far the lowest occupancy (0.33+/-0.055). Our results highlight the key tiger areas in need of protection and have led to one area (Leuser-Ulu Masen) being upgraded as a 'global priority' for wild tiger conservation. However, Sumatra has one of the highest global deforestation rates and the two largest tiger landscapes identified in this study will become highly fragmented if their respective proposed roads networks are approved. Thus, it is vital that the Indonesian government tackles these threats, e.g. through improved land-use planning, if it is to succeed in meeting its ambitious National Tiger Recovery Plan targets of doubling the number of Sumatran tigers by 2022. PMID- 22087219 TI - Next-generation sequencing of apoptotic DNA breakpoints reveals association with actively transcribed genes and gene translocations. AB - DNA fragmentation is a well-recognized hallmark of apoptosis. However, the precise DNA sequences cleaved during apoptosis triggered by distinct mechanisms remain unclear. We used next-generation sequencing of DNA fragments generated in Actinomycin D-treated human HL-60 leukemic cells to generate a high-throughput, global map of apoptotic DNA breakpoints. These data highlighted that DNA breaks are non-random and show a significant association with active genes and open chromatin regions. We noted that transcription factor binding sites were also enriched within a fraction of the apoptotic breakpoints. Interestingly, extensive apoptotic cleavage was noted within genes that are frequently translocated in human cancers. We speculate that the non-random fragmentation of DNA during apoptosis may contribute to gene translocations and the development of human cancers. PMID- 22087220 TI - G12 signaling through c-Jun NH2-terminal kinase promotes breast cancer cell invasion. AB - Signaling through the heterotrimeric G protein, G12, via Rho induces a striking increase in breast cancer cell invasion. In this study, evidence is provided that the c-Jun NH(2)-terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Expression of constitutively-active Galpha12 or activation of G12 signaling by thrombin leads to increased JNK and c-Jun phosphorylation. Pharmacologic inhibition of JNK or knockdown of JNK expression by siRNA significantly decreases G12-induced JNK activation as well as the ability of breast cancer cells to invade a reconstituted basement membrane. Furthermore, expression of dominant-negative Rho or treatment of cells with an inhibitor of the Rho kinase, ROCK, reduces G12-induced JNK and c-Jun activation, and ROCK inhibitor treatment also inhibits G12-induced cellular invasion. JNK knockdown or ROCK inhibitor treatment has no effect on activation of Rho by G12. Taken together, our data indicate that JNK activation is required for G12-induced invasion of breast cancer cells and that JNK is downstream of Rho and ROCK on this pathway. This study implicates a G12-stimulated mitogen-activated protein kinase cascade in cancer cell invasion, and supports a role for JNK in cancer progression. PMID- 22087221 TI - Contribution of NFP LysM domains to the recognition of Nod factors during the Medicago truncatula/Sinorhizobium meliloti symbiosis. AB - The root nodule nitrogen fixing symbiosis between legume plants and soil bacteria called rhizobia is of great agronomical and ecological interest since it provides the plant with fixed atmospheric nitrogen. The establishment of this symbiosis is mediated by the recognition by the host plant of lipo-chitooligosaccharides called Nod Factors (NFs), produced by the rhizobia. This recognition is highly specific, as precise NF structures are required depending on the host plant. Here, we study the importance of different LysM domains of a LysM-Receptor Like Kinase (LysM-RLK) from Medicago truncatula called Nod factor perception (NFP) in the recognition of different substitutions of NFs produced by its symbiont Sinorhizobium meliloti. These substitutions are a sulphate group at the reducing end, which is essential for host specificity, and a specific acyl chain at the non-reducing end, that is critical for the infection process. The NFP extracellular domain (ECD) contains 3 LysM domains that are predicted to bind NFs. By swapping the whole ECD or individual LysM domains of NFP for those of its orthologous gene from pea, SYM10 (a legume plant that interacts with another strain of rhizobium producing NFs with different substitutions), we showed that NFP is not directly responsible for specific recognition of the sulphate substitution of S. meliloti NFs, but probably interacts with the acyl substitution. Moreover, we have demonstrated the importance of the NFP LysM2 domain for rhizobial infection and we have pinpointed the importance of a single leucine residue of LysM2 in that step of the symbiosis. Together, our data put into new perspective the recognition of NFs in the different steps of symbiosis in M. truncatula, emphasising the probable existence of a missing component for early NF recognition and reinforcing the important role of NFP for NF recognition during rhizobial infection. PMID- 22087222 TI - Efficacy of injections with Disci/Rhus toxicodendron compositum for chronic low back pain--a randomized placebo-controlled trial. AB - BACKGROUND: The effectiveness of injection therapy for low-back pain is still debatable. We compared the efficacy of local injections of the homeopathic preparation Disci/Rhus toxicodendron compositum (verum) with placebo injections and with no treatment in patients with chronic low back pain. METHODOLOGY/PRINCIPAL FINDINGS: In a randomized controlled partly double blind multicenter trial patients with chronic low back pain from 9 German outpatient clinics were enrolled and randomly allocated in a 1?1?1 ratio to receive subcutaneous injections (verum or placebo) into painful sites on the lower back over 12 treatment sessions within eight weeks, or no treatment (rescue pain medication with paracetamol or NSAIDs). All trial personnel and participants were masked to treatment allocation. The primary outcome measure was the average pain intensity over the last seven days on a visual analogue scale (0-100 mm, 0 = no pain, 100 = worst imaginable pain) after eight weeks. Follow-up was 26 weeks. Primary analysis was by intention to treat. Between August 2007 and June 2008, 150 patients were randomly allocated to three groups (51 verum, 48 placebo and 51 no treatment). The mean baseline-adjusted low back pain intensity at week eight was: verum group 37.0 mm (97.5% CI 25.3;48.8), no treatment group 53.0 (41.8;64.2), and placebo group 41.8 (30.1;53.6). The verum was significantly superior to no treatment (P = 0.001), but not to placebo (P = 0.350). No significant side effects were reported. CONCLUSIONS/SIGNIFICANCE: The homeopathic preparation was not superior to placebo. Compared to no treatment injections resulted in significant and clinical relevant chronic back pain relief. TRIAL REGISTRATION: ClinicalTrials.gov NCT00567736. PMID- 22087223 TI - Anatomical and physiological plasticity in Leymus chinensis (Poaceae) along large scale longitudinal gradient in northeast China. AB - BACKGROUND: Although it has been widely accepted that global changes will pose the most important constrains to plant survival and distribution, our knowledge of the adaptive mechanism for plant with large-scale environmental changes (e.g. drought and high temperature) remains limited. METHODOLOGY/PRINCIPAL FINDINGS: An experiment was conducted to examine anatomical and physiological plasticity in Leymus chinensis along a large-scale geographical gradient from 115 degrees to 124 degrees E in northeast China. Ten sites selected for plant sampling at the gradient have approximately theoretical radiation, but differ in precipitation and elevation. The significantly increasing in leaf thickness, leaf mass per area, vessel and vascular diameters, and decreasing in stoma density and stoma index exhibited more obvious xerophil-liked traits for the species from the moist meadow grassland sites in contrast to that from the dry steppe and desert sites. Significant increase in proline and soluble sugar accumulation, K(+)/Na(+) for the species with the increasing of stresses along the gradient showed that osmotic adjustment was enhanced. CONCLUSION/SIGNIFICANCE: Obvious xerophytic anatomical traits and stronger osmotic adjustment in stress conditions suggested that the plants have much more anatomical and physiological flexibilities than those in non-stress habitats along the large-scale gradient. PMID- 22087224 TI - Cryosurgery with pulsed electric fields. AB - This study explores the hypothesis that combining the minimally invasive surgical techniques of cryosurgery and pulsed electric fields will eliminate some of the major disadvantages of these techniques while retaining their advantages. Cryosurgery, tissue ablation by freezing, is a well-established minimally invasive surgical technique. One disadvantage of cryosurgery concerns the mechanism of cell death; cells at high subzero temperature on the outer rim of the frozen lesion can survive. Pulsed electric fields (PEF) are another minimally invasive surgical technique in which high strength and very rapid electric pulses are delivered across cells to permeabilize the cell membrane for applications such as gene delivery, electrochemotherapy and irreversible electroporation. The very short time scale of the electric pulses is disadvantageous because it does not facilitate real time control over the procedure. We hypothesize that applying the electric pulses during the cryosurgical procedure in such a way that the electric field vector is parallel to the heat flux vector will have the effect of confining the electric fields to the frozen/cold region of tissue, thereby ablating the cells that survive freezing while facilitating controlled use of the PEF in the cold confined region. A finite element analysis of the electric field and heat conduction equations during simultaneous tissue treatment with cryosurgery and PEF (cryosurgery/PEF) was used to study the effect of tissue freezing on electric fields. The study yielded motivating results. Because of decreased electrical conductivity in the frozen/cooled tissue, it experienced temperature induced magnified electric fields in comparison to PEF delivered to the unfrozen tissue control. This suggests that freezing/cooling confines and magnifies the electric fields to those regions; a targeting capability unattainable in traditional PEF. This analysis shows how temperature induced magnified and focused PEFs could be used to ablate cells in the high subzero freezing region of a cryosurgical lesion. PMID- 22087225 TI - Biochemical and computational analysis of LNX1 interacting proteins. AB - PDZ (Post-synaptic density, 95 kDa, Discs large, Zona Occludens-1) domains are protein interaction domains that bind to the carboxy-terminal amino acids of binding partners, heterodimerize with other PDZ domains, and also bind phosphoinositides. PDZ domain containing proteins are frequently involved in the assembly of multi-protein complexes and clustering of transmembrane proteins. LNX1 (Ligand of Numb, protein X 1) is a RING (Really Interesting New Gene) domain containing E3 ubiquitin ligase that also includes four PDZ domains suggesting it functions as a scaffold for a multi-protein complex. Here we use a human protein array to identify direct LNX1 PDZ domain binding partners. Screening of 8,000 human proteins with isolated PDZ domains identified 53 potential LNX1 binding partners. We combined this set with LNX1 interacting proteins identified by other methods to assemble a list of 220 LNX1 interacting proteins. Bioinformatic analysis of this protein list was used to select interactions of interest for future studies. Using this approach we identify and confirm six novel LNX1 binding partners: KCNA4, PAK6, PLEKHG5, PKC-alpha1, TYK2 and PBK, and suggest that LNX1 functions as a signalling scaffold. PMID- 22087226 TI - Influenza-related mortality trends in Japanese and American seniors: evidence for the indirect mortality benefits of vaccinating schoolchildren. AB - BACKGROUND: The historical Japanese influenza vaccination program targeted at schoolchildren provides a unique opportunity to evaluate the indirect benefits of vaccinating high-transmitter groups to mitigate disease burden among seniors. Here we characterize the indirect mortality benefits of vaccinating schoolchildren based on data from Japan and the US. METHODS: We compared age specific influenza-related excess mortality rates in Japanese seniors aged >=65 years during the schoolchildren vaccination program (1978-1994) and after the program was discontinued (1995-2006). Indirect vaccine benefits were adjusted for demographic changes, socioeconomics and dominant influenza subtype; US mortality data were used as a control. RESULTS: We estimate that the schoolchildren vaccination program conferred a 36% adjusted mortality reduction among Japanese seniors (95%CI: 17-51%), corresponding to ~1,000 senior deaths averted by vaccination annually (95%CI: 400-1,800). In contrast, influenza-related mortality did not change among US seniors, despite increasing vaccine coverage in this population. CONCLUSIONS: The Japanese schoolchildren vaccination program was associated with substantial indirect mortality benefits in seniors. PMID- 22087227 TI - Revisiting the NMR structure of the ultrafast downhill folding protein gpW from bacteriophage lambda. AB - GpW is a 68-residue protein from bacteriophage lambda that participates in virus head morphogenesis. Previous NMR studies revealed a novel alpha+beta fold for this protein. Recent experiments have shown that gpW folds in microseconds by crossing a marginal free energy barrier (i.e., downhill folding). These features make gpW a highly desirable target for further experimental and computational folding studies. As a step in that direction, we have re-determined the high resolution structure of gpW by multidimensional NMR on a construct that eliminates the purification tags and unstructured C-terminal tail present in the prior study. In contrast to the previous work, we have obtained a full manual assignment and calculated the structure using only unambiguous distance restraints. This new structure confirms the alpha+beta topology, but reveals important differences in tertiary packing. Namely, the two alpha-helices are rotated along their main axis to form a leucine zipper. The beta-hairpin is orthogonal to the helical interface rather than parallel, displaying most tertiary contacts through strand 1. There also are differences in secondary structure: longer and less curved helices and a hairpin that now shows the typical right-hand twist. Molecular dynamics simulations starting from both gpW structures, and calculations with CS-Rosetta, all converge to our gpW structure. This confirms that the original structure has strange tertiary packing and strained secondary structure. A comparison of NMR datasets suggests that the problems were mainly caused by incomplete chemical shift assignments, mistakes in NOE assignment and the inclusion of ambiguous distance restraints during the automated procedure used in the original study. The new gpW corrects these problems, providing the appropriate structural reference for future work. Furthermore, our results are a cautionary tale against the inclusion of ambiguous experimental information in the determination of protein structures. PMID- 22087228 TI - Reduction theories elucidate the origins of complex biological rhythms generated by interacting delay-induced oscillations. AB - Time delay is known to induce sustained oscillations in many biological systems such as electroencephalogram (EEG) activities and gene regulations. Furthermore, interactions among delay-induced oscillations can generate complex collective rhythms, which play important functional roles. However, due to their intrinsic infinite dimensionality, theoretical analysis of interacting delay-induced oscillations has been limited. Here, we show that the two primary methods for finite-dimensional limit cycles, namely, the center manifold reduction in the vicinity of the Hopf bifurcation and the phase reduction for weak interactions, can successfully be applied to interacting infinite-dimensional delay-induced oscillations. We systematically derive the complex Ginzburg-Landau equation and the phase equation without delay for general interaction networks. Based on the reduced low-dimensional equations, we demonstrate that diffusive (linearly attractive) coupling between a pair of delay-induced oscillations can exhibit nontrivial amplitude death and multimodal phase locking. Our analysis provides unique insights into experimentally observed EEG activities such as sudden transitions among different phase-locked states and occurrence of epileptic seizures. PMID- 22087229 TI - Characterizing the Escherichia coli O157:H7 proteome including protein associations with higher order assemblies. AB - BACKGROUND: The recent outbreak of severe infections with Shiga toxin (Stx) producing Escherichia coli (STEC) serotype O104:H4 highlights the need to understand horizontal gene transfer among E. coli strains, identify novel virulence factors and elucidate their pathogenesis. Quantitative shotgun proteomics can contribute to such objectives, allowing insights into the part of the genome translated into proteins and the connectivity of biochemical pathways and higher order assemblies of proteins at the subcellular level. METHODOLOGY/PRINCIPAL FINDINGS: We examined protein profiles in cell lysate fractions of STEC strain 86-24 (serotype O157:H7), following growth in cell culture or bacterial isolation from intestines of infected piglets, in the context of functionally and structurally characterized biochemical pathways of E. coli. Protein solubilization in the presence of Triton X-100, EDTA and high salt was followed by size exclusion chromatography into the approximate M(r) ranges greater than 280 kDa, 280-80 kDa and 80-10 kDa. Peptide mixtures resulting from these and the insoluble fraction were analyzed by quantitative 2D-LC-nESI-MS/MS. Of the 2521 proteins identified at a 1% false discovery rate, representing 47% of all predicted E. coli O157:H7 gene products, the majority of integral membrane proteins were enriched in the high M(r) fraction. Hundreds of proteins were enriched in a M(r) range higher than that predicted for a monomer supporting their participation in protein complexes. The insoluble STEC fraction revealed enrichment of aggregation-prone proteins, including many that are part of large structure/function entities such as the ribosome, cytoskeleton and O-antigen biosynthesis cluster. SIGNIFICANCE: Nearly all E. coli O157:H7 proteins encoded by prophage regions were expressed at low abundance levels or not detected. Comparative quantitative analyses of proteins from distinct cell lysate fractions allowed us to associate uncharacterized proteins with membrane attachment, potential participation in stable protein complexes, and susceptibility to aggregation as part of larger structural assemblies. PMID- 22087230 TI - Evaluation of transmitral pressure gradients in the intraoperative echocardiographic diagnosis of mitral stenosis after mitral valve repair. AB - OBJECTIVE: Acute mitral stenosis (MS) following mitral valve (MV) repair is a rare but severe complication. We hypothesize that intraoperative echocardiography can be utilized to diagnose iatrogenic MS immediately after MV repair. METHODS: The medical records of 552 consecutive patients undergoing MV repair at a single institution were reviewed. Post-cardiopulmonary bypass peak and mean transmitral pressure gradients (TMPG), and pressure half time (PHT) were obtained from intraoperative transesophageal echocardiographic (TEE) examinations in each patient. RESULTS: Nine patients (9/552 = 1.6%) received a reoperation for primary MS, prior to hospital discharge. Interestingly, all of these patients already showed intraoperative post-CPB mean and peak TMPGs that were significantly higher compared to values for those who did not: 10.7+/-4.8 mmHg vs 2.9+/-1.6 mmHg; p<0.0001 and 22.9+/-7.9 mmHg vs 7.6+/-3.7 mmHg; p<0.0001, respectively. However, PHT varied considerably (87+/-37 ms; range: 20-439 ms) within the entire population, and only weakly predicted the requirement for reoperation (113+/-56 vs. 87+/-37 ms, p = 0.034). Receiver operating characteristic curves showed strong discriminating ability for mean gradients (AUC = 0.993) and peak gradients (area under the curve, AUC = 0.996), but poor performance for PHT (AUC = 0.640). A value of >=7 mmHg for mean, and >=17 mmHg for peak TMPG, best separated patients who required reoperation for MS from those who did not. CONCLUSIONS: Intraoperative TEE diagnosis of a peak TMPG >=17 mmHg or mean TMPG >=7 mmHg immediately following CPB are suggestive of clinically relevant MS after MV repair. PMID- 22087231 TI - Psychometric properties of the Nurses Work Functioning Questionnaire (NWFQ). AB - OBJECTIVES: The Nurses Work Functioning Questionnaire (NWFQ) is a 50-item self report questionnaire specifically developed for nurses and allied health professionals. Its seven subscales measure impairments in the work functioning due to common mental disorders. Aim of this study is to evaluate the psychometric properties of the NWFQ, by assessing reproducibility and construct validity. METHODS: The questionnaire was administered to 314 nurses and allied health professionals with a re-test in 112 subjects. Reproducibility was assessed by the intraclass correlations coefficients (ICC) and the standard error of measurement (SEM). For construct validity, correlations were calculated with a general work functioning scale, the Endicott Work Productivity Scale (EWPS) (convergent validity) and with a physical functioning scale (divergent validity). For discriminative validity, a Mann Whitney U test was performed testing for significant differences between subjects with mental health complaints and without. RESULTS: All subscales showed good reliability (ICC: 0.72-0.86), except for one (ICC = 0.16). Convergent validity was good in six subscales, correlations ranged from 0.38-0.62. However, in one subscale the correlation with the EWPS was too low (0.22). Divergent validity was good in all subscales based on correlations ranged from (-0.06)-(-0.23). Discriminative validity was good in all subscales, based on significant differences between subjects with and without mental health complaints (p<0.001-p = 0.003). CONCLUSION: The NWFQ demonstrates good psychometric properties, for six of the seven subscales. Subscale "impaired decision making" needs improvement before further use. PMID- 22087232 TI - Candida albicans yeast and hyphae are discriminated by MAPK signaling in vaginal epithelial cells. AB - We previously reported that a bi-phasic innate immune MAPK response, constituting activation of the mitogen-activated protein kinase (MAPK) phosphatase MKP1 and c Fos transcription factor, discriminates between the yeast and hyphal forms of Candida albicans in oral epithelial cells (ECs). Since the vast majority of mucosal Candida infections are vaginal, we sought to determine whether a similar bi-phasic MAPK-based immune response was activated by C. albicans in vaginal ECs. Here, we demonstrate that vaginal ECs orchestrate an innate response to C. albicans via NF-kappaB and MAPK signaling pathways. However, unlike in oral ECs, the first MAPK response, defined by c-Jun transcription factor activation, is delayed until 2 h in vaginal ECs but is still independent of hypha formation. The 'second' or 'late' MAPK response, constituting MKP1 and c-Fos transcription factor activation, is identical to oral ECs and is dependent upon both hypha formation and fungal burdens. NF-kappaB activation is immediate but independent of morphology. Furthermore, the proinflammatory response in vaginal ECs is different to oral ECs, with an absence of G-CSF and CCL20 and low level IL-6 production. Therefore, differences exist in how C. albicans activates signaling mechanisms in oral and vaginal ECs; however, the activation of MAPK-based pathways that discriminate between yeast and hyphal forms is retained between these mucosal sites. We conclude that this MAPK-based signaling pathway is a common mechanism enabling different human epithelial tissues to orchestrate innate immune responses specifically against C. albicans hyphae. PMID- 22087233 TI - Massively parallel amplicon sequencing reveals isotype-specific variability of antimicrobial peptide transcripts in Mytilus galloprovincialis. AB - BACKGROUND: Effective innate responses against potential pathogens are essential in the living world and possibly contributed to the evolutionary success of invertebrates. Taken together, antimicrobial peptide (AMP) precursors of defensin, mytilin, myticin and mytimycin can represent about 40% of the hemocyte transcriptome in mussels injected with viral-like and bacterial preparations, and unique profiles of myticin C variants are expressed in single mussels. Based on amplicon pyrosequencing, we have ascertained and compared the natural and Vibrio induced diversity of AMP transcripts in mussel hemocytes from three European regions. METHODOLOGY/PRINCIPAL FINDINGS: Hemolymph was collected from mussels farmed in the coastal regions of Palavas (France), Vigo (Spain) and Venice (Italy). To represent the AMP families known in M. galloprovincialis, nine transcript sequences have been selected, amplified from hemocyte RNA and subjected to pyrosequencing. Hemolymph from farmed (offshore) and wild (lagoon) Venice mussels, both injected with 10(7) Vibrio cells, were similarly processed. Amplicon pyrosequencing emphasized the AMP transcript diversity, with Single Nucleotide Changes (SNC) minimal for mytilin B/C and maximal for arthropod-like defensin and myticin C. Ratio of non-synonymous vs. synonymous changes also greatly differed between AMP isotypes. Overall, each amplicon revealed similar levels of nucleotidic variation across geographical regions, with two main sequence patterns confirmed for mytimycin and no substantial changes after immunostimulation. CONCLUSIONS/SIGNIFICANCE: Barcoding and bidirectional pyrosequencing allowed us to map and compare the transcript diversity of known mussel AMPs. Though most of the genuine cds variation was common to the analyzed samples we could estimate from 9 to 106 peptide variants in hemolymph pools representing 100 mussels, depending on the AMP isoform and sampling site. In this study, no prevailing SNC patterns related to geographical origin or Vibrio injection emerged. Whether or not the contact with potential pathogens can increase the amount of AMP transcript variants in mussels requires additional study. PMID- 22087234 TI - Wnt signaling cross-talks with JH signaling by suppressing Met and gce expression. AB - Juvenile hormone (JH) plays key roles in controlling insect growth and metamorphosis. However, relatively little is known about the JH signaling pathways. Until recent years, increasing evidence has suggested that JH modulates the action of 20-hydroxyecdysone (20E) by regulating expression of broad (br), a 20E early response gene, through Met/Gce and Kr-h1. To identify other genes involved in JH signaling, we designed a novel Drosophila genetic screen to isolate mutations that derepress JH-mediated br suppression at early larval stages. We found that mutations in three Wnt signaling negative regulators in Drosophila, Axin (Axn), supernumerary limbs (slmb), and naked cuticle (nkd), caused precocious br expression, which could not be blocked by exogenous JHA. A similar phenotype was observed when armadillo (arm), the mediator of Wnt signaling, was overexpressed. qRT-PCR revealed that Met, gce and Kr-h1expression was suppressed in the Axn, slmb and nkd mutants as well as in arm gain-of function larvae. Furthermore, ectopic expression of gce restored Kr-h1 expression but not Met expression in the arm gain-of-function larvae. Taken together, we conclude that Wnt signaling cross-talks with JH signaling by suppressing transcription of Met and gce, genes that encode for putative JH receptors. The reduced JH activity further induces down-regulation of Kr-h1expression and eventually derepresses br expression in the Drosophila early larval stages. PMID- 22087235 TI - A focused in situ hybridization screen identifies candidate transcriptional regulators of thymic epithelial cell development and function. AB - BACKGROUND: Thymic epithelial cells (TECs) are necessary for normal T cell development. Currently, one transcription factor, Foxn1 is known to be necessary for the progression of fetal TEC differentiation. However, some aspects of fetal TEC differentiation occur in Foxn1 mutants, suggesting the existence of additional transcriptional regulators of TEC differentiation. The goal of this study was to identify some of the additional candidate transcription factors that may be involved in the specification and/or differentiation of TECs during fetal development. METHODOLOGY/PRINCIPAL FINDINGS: We identified candidate fetal TEC transcriptional regulators via data and text mining. From our data mining we selected the transcription factors Foxg1, Isl1, Gata3, Nkx2-5, Nkx2-6 and Sox2 for further studies. Whole mount in situ hybridizations confirmed the expression of these transcription factors within subdomains of the third pharyngeal pouch from E9.5-E10.5. By E11.5 days Foxg1 and Isl1 transcripts were the only mRNAs from this group of genes detected exclusively within the thymus domain of the third pouch. Based on this initial in situ hybridization analysis, we focused on defining the expression of Foxg1 and Isl1 during multiple stages of thymus development and TEC differentiation. We found that Foxg1 and Isl1 are specifically expressed in differentiating TECs during fetal and postnatal stages of thymus development. In addition, we found differential expression of Islet1 and Foxn1 within the fetal and postnatal TEC population. CONCLUSIONS/SIGNIFICANCE: Our studies have identified two developmental transcription factors that are excellent candidate regulators of thymic epithelial cell specification and differentiation during fetal development. Our results suggest that Foxg1 and Isl1 may play a role in the regulation of TEC differentiation during fetal and postnatal stages. Our results also demonstrate heterogeneity of TECs marked by the differential expression of transcription factors, potentially providing new insights into the regulation of TEC differentiation. PMID- 22087236 TI - Induction of PGC-1alpha expression can be detected in blood samples of patients with ST-segment elevation acute myocardial infarction. AB - Following acute myocardial infarction (MI), cardiomyocyte survival depends on its mitochondrial oxidative capacity. Cell death is normally followed by activation of the immune system. Peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) is a transcriptional coactivator and a master regulator of cardiac oxidative metabolism. PGC-1alpha is induced by hypoxia and facilitates the recovery of the contractile capacity of the cardiac muscle following an artery ligation procedure. We hypothesized that PGC-1alpha activity could serve as a good molecular marker of cardiac recovery after a coronary event. The objective of the present study was to monitor the levels of PGC-1alpha following an ST-segment elevation acute myocardial infarction (STEMI) episode in blood samples of the affected patients. Analysis of blood mononuclear cells from human patients following an STEMI showed that PGC-1alpha expression was increased and the level of induction correlated with the infarct size. Infarct size was determined by LGE-CMR (late gadolinium enhancement on cardiac magnetic resonance), used to estimate the percentage of necrotic area. Cardiac markers, maximum creatine kinase (CK-MB) and Troponin I (TnI) levels, left ventricular ejection function (LVEF) and regional wall motion abnormalities (RWMA) as determined by echocardiography were also used to monitor cardiac injury. We also found that PGC-1alpha is present and active in mouse lymphocytes where its expression is induced upon activation and can be detected in the nuclear fraction of blood samples. These results support the notion that induction of PGC-1alpha expression can be part of the recovery response to an STEMI and could serve as a prognosis factor of cardiac recovery. PMID- 22087237 TI - Improving the estimation of celiac disease sibling risk by non-HLA genes. AB - Celiac Disease (CD) is a polygenic trait, and HLA genes explain less than half of the genetic variation. Through large GWAs more than 40 associated non-HLA genes were identified, but they give a small contribution to the heritability of the disease. The aim of this study is to improve the estimate of the CD risk in siblings, by adding to HLA a small set of non-HLA genes. One-hundred fifty-seven Italian families with a confirmed CD case and at least one other sib and both parents were recruited. Among 249 sibs, 29 developed CD in a 6 year follow-up period. All individuals were typed for HLA and 10 SNPs in non-HLA genes: CCR1/CCR3 (rs6441961), IL12A/SCHIP1 and IL12A (rs17810546 and rs9811792), TAGAP (rs1738074), RGS1 (rs2816316), LPP (rs1464510), OLIG3 (rs2327832), REL (rs842647), IL2/IL21 (rs6822844), SH2B3 (rs3184504). Three associated SNPs (in LPP, REL, and RGS1 genes) were identified through the Transmission Disequilibrium Test and a Bayesian approach was used to assign a score (BS) to each detected HLA+SNPs genotype combination. We then classified CD sibs as at low or at high risk if their BS was respectively < or >= median BS value within each HLA risk group. A larger number (72%) of CD sibs showed a BS >= the median value and had a more than two fold higher OR than CD sibs with a BS value < the median (O.R = 2.53, p = 0.047). Our HLA+SNPs genotype classification, showed both a higher predictive negative value (95% vs 91%) and diagnostic sensitivity (79% vs 45%) than the HLA only. In conclusion, the estimate of the CD risk by HLA+SNPs approach, even if not applicable to prevention, could be a precious tool to improve the prediction of the disease in a cohort of first degree relatives, particularly in the low HLA risk groups. PMID- 22087238 TI - A bayesian mixed regression based prediction of quantitative traits from molecular marker and gene expression data. AB - Both molecular marker and gene expression data were considered alone as well as jointly to serve as additive predictors for two pathogen-activity-phenotypes in real recombinant inbred lines of soybean. For unobserved phenotype prediction, we used a bayesian hierarchical regression modeling, where the number of possible predictors in the model was controlled by different selection strategies tested. Our initial findings were submitted for DREAM5 (the 5th Dialogue on Reverse Engineering Assessment and Methods challenge) and were judged to be the best in sub-challenge B3 wherein both functional genomic and genetic data were used to predict the phenotypes. In this work we further improve upon this previous work by considering various predictor selection strategies and cross-validation was used to measure accuracy of in-data and out-data predictions. The results from various model choices indicate that for this data use of both data types (namely functional genomic and genetic) simultaneously improves out-data prediction accuracy. Adequate goodness-of-fit can be easily achieved with more complex models for both phenotypes, since the number of potential predictors is large and the sample size is not small. We also further studied gene-set enrichment (for continuous phenotype) in the biological process in question and chromosomal enrichment of the gene set. The methodological contribution of this paper is in exploration of variable selection techniques to alleviate the problem of over fitting. Different strategies based on the nature of covariates were explored and all methods were implemented under the bayesian hierarchical modeling framework with indicator-based covariate selection. All the models based in careful variable selection procedure were found to produce significant results based on permutation test. PMID- 22087239 TI - Genome-wide functional analysis of the cotton transcriptome by creating an integrated EST database. AB - A total of 28,432 unique contigs (25,371 in consensus contigs and 3,061 as singletons) were assembled from all 268,786 cotton ESTs currently available. Several in silico approaches [comparative genomics, Blast, Gene Ontology (GO) analysis, and pathway enrichment by Kyoto Encyclopedia of Genes and Genomes (KEGG)] were employed to investigate global functions of the cotton transcriptome. Cotton EST contigs were clustered into 5,461 groups with a maximum cluster size of 196 members. A total of 27,956 indel mutants and 149,616 single nucleotide polymorphisms (SNPs) were identified from consensus contigs. Interestingly, many contigs with significantly high frequencies of indels or SNPs encode transcription factors and protein kinases. In a comparison with six model plant species, cotton ESTs show the highest overall similarity to grape. A total of 87 cotton miRNAs were identified; 59 of these have not been reported previously from experimental or bioinformatics investigations. We also predicted 3,260 genes as miRNAs targets, which are associated with multiple biological functions, including stress response, metabolism, hormone signal transduction and fiber development. We identified 151 and 4,214 EST-simple sequence repeats (SSRs) from contigs and raw ESTs respectively. To make these data widely available, and to facilitate access to EST-related genetic information, we integrated our results into a comprehensive, fully downloadable web-based cotton EST database (www.leonxie.com). PMID- 22087240 TI - Post eclosion age predicts the prevalence of midgut trypanosome infections in Glossina. AB - The teneral phenomenon, as observed in Glossina sp., refers to the increased susceptibility of the fly to trypanosome infection when the first bloodmeal taken is trypanosome-infected. In recent years, the term teneral has gradually become synonymous with unfed, and thus fails to consider the age of the newly emerged fly at the time the first bloodmeal is taken. Furthermore, conflicting evidence exists of the effect of the age of the teneral fly post eclosion when it is given the infected first bloodmeal in determining the infection prevalence. This study demonstrates that it is not the feeding history of the fly but rather the age (hours after eclosion of the fly from the puparium) of the fly when it takes the first (infective) bloodmeal that determines the level of fly susceptibility to trypanosome infection. We examine this phenomenon in male and female flies from two distinct tsetse clades (Glossina morsitans morsitans and Glossina palpalis palpalis) infected with two salivarian trypanosome species, Trypanosoma (Trypanozoon) brucei brucei and Trypanosoma (Nannomonas) congolense using Fisher's exact test to examine differences in infection rates. Teneral tsetse aged less than 24 hours post-eclosion (h.p.e.) are twice as susceptible to trypanosome infection as flies aged 48 h.p.e. This trend is conserved across sex, vector clade and parasite species. The life cycle stage of the parasite fed to the fly (mammalian versus insect form trypanosomes) does not alter this age related bias in infection. Reducing the numbers of parasites fed to 48 h.p.e., but not to 24 h.p.e. flies, increases teneral refractoriness. The importance of this phenomenon in disease biology in the field as well as the necessity of employing flies of consistent age in laboratory-based infection studies is discussed. PMID- 22087241 TI - Rosiglitazone-induced mitochondrial biogenesis in white adipose tissue is independent of peroxisome proliferator-activated receptor gamma coactivator 1alpha. AB - BACKGROUND: Thiazolidinediones, a family of insulin-sensitizing drugs commonly used to treat type 2 diabetes, are thought to exert their effects in part by promoting mitochondrial biogenesis in white adipose tissue through the transcriptional coactivator PGC-1alpha (Peroxisome Proliferator-Activated Receptor gamma Coactivator-1alpha). METHODOLOGY/PRINCIPAL FINDINGS: To assess the role of PGC-1alpha in the control of rosiglitazone-induced mitochondrial biogenesis, we have generated a mouse model that lacks expression of PGC-1alpha specifically in adipose tissues (PGC-1alpha-FAT-KO mice). We found that expression of genes encoding for mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle or fatty acid oxidation, was similar in white adipose tissue of wild type and PGC-1alpha-FAT-KO mice. Furthermore, the absence of PGC-1alpha did not prevent the positive effect of rosiglitazone on mitochondrial gene expression or biogenesis, but it precluded the induction by rosiglitazone of UCP1 and other brown fat-specific genes in white adipose tissue. Consistent with the in vivo findings, basal and rosiglitazone-induced mitochondrial gene expression in 3T3-L1 adipocytes was unaffected by the knockdown of PGC-1alpha but it was impaired when PGC-1beta expression was knockdown by the use of specific siRNA. CONCLUSIONS/SIGNIFICANCE: These results indicate that in white adipose tissue PGC-1alpha is dispensable for basal and rosiglitazone-induced mitochondrial biogenesis but required for the rosiglitazone induced expression of UCP1 and other brown adipocyte-specific markers. Our study suggests that PGC-1alpha is important for the appearance of brown adipocytes in white adipose tissue. Our findings also provide evidence that PGC-1beta and not PGC-1alpha regulates basal and rosiglitazone-induced mitochondrial gene expression in white adipocytes. PMID- 22087242 TI - Classification of sharks in the Egyptian Mediterranean waters using morphological and DNA barcoding approaches. AB - The identification of species constitutes the first basic step in phylogenetic studies, biodiversity monitoring and conservation. DNA barcoding, i.e. the sequencing of a short standardized region of DNA, has been proposed as a new tool for animal species identification. The present study provides an update on the composition of shark in the Egyptian Mediterranean waters off Alexandria, since the latest study to date was performed 30 years ago, DNA barcoding was used in addition to classical taxonomical methodologies. Thus, 51 specimen were DNA barcoded for a 667 bp region of the mitochondrial COI gene. Although DNA barcoding aims at developing species identification systems, some phylogenetic signals were apparent in the data. In the neighbor-joining tree, 8 major clusters were apparent, each of them containing individuals belonging to the same species, and most with 100% bootstrap value. This study is the first to our knowledge to use DNA barcoding of the mitochondrial COI gene in order to confirm the presence of species Squalus acanthias, Oxynotus centrina, Squatina squatina, Scyliorhinus canicula, Scyliorhinus stellaris, Mustelus mustelus, Mustelus punctulatus and Carcharhinus altimus in the Egyptian Mediterranean waters. Finally, our study is the starting point of a new barcoding database concerning shark composition in the Egyptian Mediterranean waters (Barcoding of Egyptian Mediterranean Sharks [BEMS], http://www.boldsystems.org/views/projectlist.php?&#Barcoding%20Fish%20%28FishBOL% 9). PMID- 22087243 TI - Features, causes and consequences of splanchnic sequestration of amino acid in old rats. AB - RATIONALE: In elderly subjects, splanchnic extraction of amino acids (AA) increases during meals in a process known as splanchnic sequestration of amino acids (SSAA). This process potentially contributes to the age-related progressive decline in muscle mass via reduced peripheral availability of dietary AA. SSAA mechanisms are unknown but may involve an increased net utilization of ingested AA in the splanchnic area. OBJECTIVES: Using stable isotope methodology in fed adult and old rats to provide insight into age-related SSAA using three hypotheses: 1) an increase in protein synthesis in the gut and/or the liver, 2) an increase in AA oxidation related to an increased ureagenesis, and 3) Kupffer cell (KC) activation consequently to age-related low-grade inflammation. FINDINGS: Splanchnic extraction of Leu (SPELeu) was doubled in old rats compared to adult rats and was not changed after KC inactivation. No age-related effects on gut and liver protein synthesis were observed, but urea synthesis was lower in old rats and negatively correlated to liver Arg utilization. Net whole-body protein synthesis and arterial AA levels were lower in old rats and correlated negatively with SPELeu. CONCLUSION: SSAA is not the consequence of age-related alterations in ureagenesis, gut or liver protein synthesis or of KC activity. However, SSAA may be related to reduced net whole-body protein synthesis and consequently to the reduced lean body mass that occurs during aging. PMID- 22087244 TI - A molecular phylogeny of the Chalcidoidea (Hymenoptera). AB - Chalcidoidea (Hymenoptera) are extremely diverse with more than 23,000 species described and over 500,000 species estimated to exist. This is the first comprehensive phylogenetic analysis of the superfamily based on a molecular analysis of 18S and 28S ribosomal gene regions for 19 families, 72 subfamilies, 343 genera and 649 species. The 56 outgroups are comprised of Ceraphronoidea and most proctotrupomorph families, including Mymarommatidae. Data alignment and the impact of ambiguous regions are explored using a secondary structure analysis and automated (MAFFT) alignments of the core and pairing regions and regions of ambiguous alignment. Both likelihood and parsimony approaches are used to analyze the data. Overall there is no impact of alignment method, and few but substantial differences between likelihood and parsimony approaches. Monophyly of Chalcidoidea and a sister group relationship between Mymaridae and the remaining Chalcidoidea is strongly supported in all analyses. Either Mymarommatoidea or Diaprioidea are the sister group of Chalcidoidea depending on the analysis. Likelihood analyses place Rotoitidae as the sister group of the remaining Chalcidoidea after Mymaridae, whereas parsimony nests them within Chalcidoidea. Some traditional family groups are supported as monophyletic (Agaonidae, Eucharitidae, Encyrtidae, Eulophidae, Leucospidae, Mymaridae, Ormyridae, Signiphoridae, Tanaostigmatidae and Trichogrammatidae). Several other families are paraphyletic (Perilampidae) or polyphyletic (Aphelinidae, Chalcididae, Eupelmidae, Eurytomidae, Pteromalidae, Tetracampidae and Torymidae). Evolutionary scenarios discussed for Chalcidoidea include the evolution of phytophagy, egg parasitism, sternorrhynchan parasitism, hypermetamorphic development and heteronomy. PMID- 22087245 TI - Serum microRNA expression profile distinguishes enterovirus 71 and coxsackievirus 16 infections in patients with hand-foot-and-mouth disease. AB - Altered circulating microRNA (miRNA) profiles have been noted in patients with microbial infections. We compared host serum miRNA levels in patients with hand foot-and-mouth disease (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) as well as in other microbial infections and in healthy individuals. Among 664 different miRNAs analyzed using a miRNA array, 102 were up-regulated and 26 were down-regulated in sera of patients with enteroviral infections. Expression levels of ten candidate miRNAs were further evaluated by quantitative real-time PCR assays. A receiver operating characteristic (ROC) curve analysis revealed that six miRNAs (miR-148a, miR-143, miR-324-3p, miR-628-3p, miR-140-5p, and miR-362-3p) were able to discriminate patients with enterovirus infections from healthy controls with area under curve (AUC) values ranged from 0.828 to 0.934. The combined six miRNA using multiple logistic regression analysis provided not only a sensitivity of 97.1% and a specificity of 92.7% but also a unique profile that differentiated enterovirial infections from other microbial infections. Expression levels of five miRNAs (miR-148a, miR-143, miR-324-3p, miR 545, and miR-140-5p) were significantly increased in patients with CVA16 versus those with EV71 (p<0.05). Combination of miR-545, miR-324-3p, and miR-143 possessed a moderate ability to discrimination between CVA16 and EV71 with an AUC value of 0.761. These data indicate that sera from patients with different subtypes of enteroviral infection express unique miRNA profiles. Serum miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping enteroviral HFMD infections. PMID- 22087246 TI - High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. AB - Multiple lines of evidence suggest that a large portion of pancreatic cancer patients suffer from either hyperglycemia or diabetes, both of which are characterized by high blood glucose level. However, the underlying biological mechanism of this phenomenon is largely unknown. In the present study, we demonstrated that the proliferative ability of two human pancreatic cancer cell lines, BxPC-3 and Panc-1, was upregulated by high glucose in a concentration dependent manner. Furthermore, the promoting effect of high glucose levels on EGF transcription and secretion but not its receptors in these PC cell lines was detected by using an EGF-neutralizing antibody and RT-PCR. In addition, the EGFR transactivation is induced by high glucose levels in concentration- and time dependent manners in PC cells in the presence of the EGF-neutralizing antibody. These results suggest that high glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. Our findings may provide new insight on the links between high glucose level and PC in terms of the molecular mechanism and reveal a novel therapeutic strategy for PC patients who simultaneously suffer from either diabetes or hyperglycemia. PMID- 22087247 TI - Extracellular matrix from porcine small intestinal submucosa (SIS) as immune adjuvants. AB - Porcine small intestinal submucosa (SIS) of Cook Biotech is licensed and widely used for tissue remodeling in humans. SIS was shown to be highly effective as an adjuvant in model studies with prostate and ovarian cancer vaccines. However, SIS adjuvanticity relative to alum, another important human-licensed adjuvant, has not yet been delineated in terms of activation of innate immunity via inflammasomes and boosting of antibody responses to soluble proteins and hapten protein conjugates. We used ovalbumin, and a hapten-protein conjugate, phthalate keyhole limpet hemocyanin. The evaluation of SIS was conducted in BALB/c and C57BL/6 mice using both intraperitoneal and subcutaneous routes. Inflammatory responses were studied by microarray profiling of chemokines and cytokines and by qPCR of inflammasomes-related genes. Results showed that SIS affected cytokine and chemokines microenvironments such as up-regulation of IL-4 and CD30-ligand and activation of chemotactic factors LIX and KC (neutrophil chemotactic factors), MCP-1 (monocytes chemotactic factors), MIP 1-alpha (macrophage chemotactic factor) and lymphotactin, as well as, growth factors like M-CSF. SIS also promoted gene expression of Nod-like receptors (NLR) and associated downstream effectors. However, in contrast to alum, SIS had no effects on pro inflammatory cytokines (IL-6, IL-1beta, TNF-alpha) or NLRP3, but it appeared to promote both Th1 and Th2 responses under different conditions. Lastly, it was as effective as alum in engendering a lasting and specific antibody response, primarily of IgG1 type. PMID- 22087248 TI - The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis. AB - BACKGROUND: An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC). METHODS: We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV)-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection. RESULTS: PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001) increased in alcoholic cirrhosis with (53.7%) and without HCC (36.2%) but was not different between healthy controls (22.9%) and patients with cirrhosis (25.3%; p = 0.545) and HCC (30.2%; p = 0.071) due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR) 16.8 versus healthy controls; 95% confidence interval (CI) 6.68-42.43, p<0.001). Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24-6.42; p = 0.013) as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50-11.52; p = 0.006). CONCLUSION: The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that should be taken into account in future HCC prevention studies. PMID- 22087249 TI - Nutrient sensing kinases PKA and Sch9 phosphorylate the catalytic domain of the ubiquitin-conjugating enzyme Cdc34. AB - Cell division is controlled in part by the timely activation of the CDK, Cdc28, through its association with G1 and G2 cyclins. Cdc28 complexes are regulated in turn by the ubiquitin conjugating enzyme Cdc34 and SCF ubiquitin ligase complexes of the ubiquitin-proteasome system (UPS) to control the initiation of DNA replication. Here we demonstrate that the nutrient sensing kinases PKA and Sch9 phosphorylate S97 of Cdc34. S97 is conserved across species and restricted to the catalytic domain of Cdc34/Ubc7-like E2s. Cdc34-S97 phosphorylation is cell cycle regulated, elevated during active cell growth and division and decreased during cell cycle arrest. Cell growth and cell division are orchestrated to maintain cell size homeostasis over a wide range of nutrient conditions. Cells monitor changes in their environment through nutrient sensing protein kinases. Thus Cdc34 phosphorylation by PKA and Sch9 provides a direct tether between G1 cell division events and cell growth. PMID- 22087250 TI - Elevated levels of the vesicular monoamine transporter and a novel repetitive behavior in the Drosophila model of fragile X syndrome. AB - Fragile X Syndrome (FXS) is characterized by mental impairment and autism in humans, and it often features hyperactivity and repetitive behaviors. The mechanisms for the disease, however, remain poorly understood. Here we report that the dfmr1 mutant in the Drosophila model of FXS grooms excessively, which may be regulated differentially by two signaling pathways. Blocking metabotropic glutamate receptor signaling enhances grooming in dfmr1 mutant flies, whereas blocking the vesicular monoamine transporter (VMAT) suppresses excessive grooming. dfmr1 mutant flies also exhibit elevated levels of VMAT mRNA and protein. These results suggest that enhanced monoamine signaling correlates with repetitive behaviors and hyperactivity associated with FXS. PMID- 22087251 TI - Prolyl hydroxylase PHD3 enhances the hypoxic survival and G1 to S transition of carcinoma cells. AB - Hypoxia restricts cell proliferation and cell cycle progression at the G1/S interface but at least a subpopulation of carcinoma cells can escape the restriction. In carcinoma hypoxia may in fact select for cells with enhanced hypoxic survival and increased aggressiveness. The cellular oxygen sensors HIF proline hydroxylases (PHDs) adapt the cellular functions to lowered environmental oxygen tension. PHD3 isoform has shown the strongest hypoxic upregulation among the family members. We detected a strong PHD3 mRNA expression in tumors of head and neck squamous cell carcinoma (HNSCC). The PHD3 expression associated with expression of hypoxic marker gene. Using siRNA in cell lines derived from HNSCC we show that specific inhibition of PHD3 expression in carcinoma cells caused reduced cell survival in hypoxia. The loss of PHD3, but not that of PHD2, led to marked cell number reduction. Although caspase-3 was activated at early hypoxia no induction of apoptosis was detected. However, hypoxic PHD3 inhibition caused a block in cell cycle progression. Cell population in G1 phase was increased and the population in S phase reduced demonstrating a block in G1 to S transition under PHD3 inhibition. In line with this, the level of hyperphosphorylated retinoblastoma protein Rb was reduced by PHD3 knock-down in hypoxia. PHD3 loss led to increase in cyclin-dependent kinase inhibitor p27 expression but not that of p21 or p16. The data demonstrated that increased PHD3 expression under hypoxia enhances cell cycle progression and survival of carcinoma cells. PMID- 22087252 TI - Increasing genetic variance of body mass index during the Swedish obesity epidemic. AB - BACKGROUND AND OBJECTIVES: There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin and family studies suggest that genetic differences are responsible for the major part of the variation in adiposity within populations. Recent studies show that the genetic effects on body mass index (BMI) may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that the genetic variance of BMI has increased during the obesity epidemic. METHODS: The data comprised height and weight measurements of 1,474,065 Swedish conscripts at age 18-19 y born between 1951 and 1983. The data were linked to the Swedish Multi Generation Register and the Swedish Twin Register from which 264,796 full-brother pairs, 1,736 monozygotic (MZ) and 1,961 dizygotic (DZ) twin pairs were identified. The twin pairs were analysed to identify the most parsimonious model for the genetic and environmental contribution to BMI variance. The full-brother pairs were subsequently divided into subgroups by year of birth to investigate trends in the genetic variance of BMI. RESULTS: The twin analysis showed that BMI variation could be explained by additive genetic and environmental factors not shared by co-twins. On the basis of the analyses of the full-siblings, the additive genetic variance of BMI increased from 4.3 [95% CI 4.04-4.53] to 7.9 [95% CI 7.28-8.54] within the study period, as did the unique environmental variance, which increased from 1.4 [95% CI 1.32-1.48] to 2.0 [95% CI 1.89-2.22]. The BMI heritability increased from 75% to 78.8%. CONCLUSION: The results confirm the hypothesis that the additive genetic variance of BMI has increased strongly during the obesity epidemic. This suggests that the obesogenic environment has enhanced the influence of adiposity related genes. PMID- 22087253 TI - Functional characterization and cellular dynamics of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. AB - Rho-type GTPases are key regulators that control eukaryotic cell polarity, but their role in fungal morphogenesis is only beginning to emerge. In this study, we investigate the role of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. rac and cdc-42 deletion mutants are viable, but generate highly compact colonies with severe morphological defects. Double mutants carrying conditional and loss of function alleles of rac and cdc-42 are lethal, indicating that both GTPases share at least one common essential function. The defects of the GTPase mutants are phenocopied by deletion and conditional alleles of the guanine exchange factor (GEF) cdc-24, and in vitro GDP-GTP exchange assays identify CDC-24 as specific GEF for both CDC-42 and RAC. In vivo confocal microscopy shows that this module is organized as membrane-associated cap that covers the hyphal apex. However, the specific localization patterns of the three proteins are distinct, indicating different functions of RAC and CDC-42 within the hyphal tip. CDC-42 localized as confined apical membrane-associated crescent, while RAC labeled a membrane-associated ring excluding the region labeled by CDC42. The GEF CDC-24 occupied a strategic position, localizing as broad apical membrane-associated crescent and in the apical cytosol excluding the Spitzenkorper. RAC and CDC-42 also display distinct localization patterns during branch initiation and germ tube formation, with CDC-42 accumulating at the plasma membrane before RAC. Together with the distinct cellular defects of rac and cdc-42 mutants, these localizations suggest that CDC-42 is more important for polarity establishment, while the primary function of RAC may be maintaining polarity. In summary, this study identifies CDC-24 as essential regulator for RAC and CDC-42 that have common and distinct functions during polarity establishment and maintenance of cell polarity in N. crassa. PMID- 22087254 TI - Direct transcriptional control of a p38 MAPK pathway by the circadian clock in Neurospora crassa. AB - MAPK signal transduction pathways are important regulators of stress responses, cellular growth, and differentiation. In Neurospora, the circadian clock controls rhythms in phosphorylation of the p38-like MAPK (OS-2); however, the mechanism for this regulation is not known. We show that the WCC, a transcription factor and clock component, binds to the os-4 MAPKKK promoter in response to light and rhythmically in constant darkness, peaking in the subjective morning. Deletion of the WCC binding sites in the os-4 promoter disrupts both os-4 mRNA and OS-2 phosphorylation rhythms. The clock also indirectly regulates rhythmic expression of the histidyl-phosphotransferase gene, hpt-1, which peaks in the evening. Anti phase expression of positive (OS-4) and negative (HPT-1) MAPK pathway regulators likely coordinate to enhance rhythmic MAPK activation to prepare cells to respond to osmotic stress during the day in the natural environment. Consistent with this idea, we show that wild type cells have a clock-dependent morning kinetic advantage in glycerol accumulation after salt stress as compared to evening treatment. Thus, circadian transcriptional control of MAPK pathway components leads to striking time-of-day-specific effects on the signaling status and physiological response of the pathway. PMID- 22087255 TI - Characterization of non-specific cytotoxic cell receptor protein 1: a new member of the lectin-type subfamily of F-box proteins. AB - Our previous microarray study showed that the non-specific cytotoxic cell receptor protein 1 (Nccrp1) transcript is significantly upregulated in the gastric mucosa of carbonic anhydrase IX (CA IX)-deficient (Car9(-/-)) mice. In this paper, we aimed to characterize human NCCRP1 and to elucidate its relationship to CA IX. Recombinant NCCRP1 protein was expressed in Escherichia coli, and a novel polyclonal antiserum was raised against the purified full length protein. Immunocytochemistry showed that NCCRP1 is expressed intracellularly, even though it has previously been described as a transmembrane protein. Using bioinformatic analyses, we identified orthologs of NCCRP1 in 35 vertebrate genomes, and up to five paralogs per genome. These paralogs are FBXO genes whose protein products are components of the E3 ubiquitin ligase complexes. NCCRP1 proteins have no signal peptides or transmembrane domains. NCCRP1 has mainly been studied in fish and was thought to be responsible for the cytolytic function of nonspecific cytotoxic cells (NCCs). Our analyses showed that in humans, NCCRP1 mRNA is expressed in tissues containing squamous epithelium, whereas it shows a more ubiquitous tissue expression pattern in mice. Neither human nor mouse NCCRP1 expression is specific to immune tissues. Silencing CA9 using siRNAs did not affect NCCRP1 levels, indicating that its expression is not directly regulated by CA9. Interestingly, silencing NCCRP1 caused a statistically significant decrease in the growth of HeLa cells. These studies provide ample evidence that the current name, "non-specific cytotoxic cell receptor protein 1," is not appropriate. We therefore propose that the gene name be changed to FBXO50. PMID- 22087256 TI - Versatile roles of V-ATPases accessory subunit Ac45 in osteoclast formation and function. AB - Vacuolar-type H(+)-ATPases (V-ATPases) are macromolecular proton pumps that acidify intracellular cargos and deliver protons across the plasma membrane of a variety of specialized cells, including bone-resorbing osteoclasts. Extracellular acidification is crucial for osteoclastic bone resorption, a process that initiates the dissolution of mineralized bone matrix. While the importance of V ATPases in osteoclastic resorptive function is well-defined, whether V-ATPases facilitate additional aspects of osteoclast function and/or formation remains largely obscure. Here we report that the V-ATPase accessory subunit Ac45 participates in both osteoclast formation and function. Using a siRNA-based approach, we show that targeted suppression of Ac45 impairs intracellular acidification and endocytosis, both are prerequisite for osteoclastic bone resorptive function in vitro. Interestingly, we find that knockdown of Ac45 also attenuates osteoclastogenesis owing to a reduced fusion capacity of osteoclastic precursor cells. Finally, in an effort to gain more detailed insights into the functional role of Ac45 in osteoclasts, we attempted to generate osteoclast specific Ac45 conditional knockout mice using a Cathepsin K-Cre-LoxP system. Surprisingly, however, insertion of the neomycin cassette in the Ac45-Flox(Neo) mice resulted in marked disturbances in CNS development and ensuing embryonic lethality thus precluding functional assessment of Ac45 in osteoclasts and peripheral bone tissues. Based on these unexpected findings we propose that, in addition to its canonical function in V-ATPase-mediated acidification, Ac45 plays versatile roles during osteoclast formation and function. PMID- 22087257 TI - Association of the sirtuin and mitochondrial uncoupling protein genes with carotid plaque. AB - OBJECTIVE: Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in cardiovascular diseases through the control of reactive oxygen species production. This study sought to investigate the association between genetic variants in the SIRT and UCP genes and carotid plaque. METHODS: In a group of 1018 stroke-free subjects from the Northern Manhattan Study with high definition carotid ultrasonography and genotyping, we investigated the associations of 85 single nucleotide polymorphisms (SNPs) in the 11 SIRT and UCP genes with the presence and number of carotid plaques, and evaluated interactions of SNPs with sex, smoking, diabetes and hypertension as well as interactions between SNPs significantly associated with carotid plaque. RESULTS: Overall, 60% of subjects had carotid plaques. After adjustment for demographic and vascular risk factors, T-carriers of the SIRT6 SNP rs107251 had an increased risk for carotid plaque (odds ratio, OR = 1.71, 95% CI = 1.23-2.37, Bonferroni-corrected p = 0.03) and for a number of plaques (rate ratio, RR = 1.31, 1.18-1.45, Bonferroni corrected p = 1.4*10(-5)), whereas T-carriers of the UCP5 SNP rs5977238 had an decreased risk for carotid plaque (OR = 0.49, 95% CI = 0.32-0.74, Bonferroni corrected p = 0.02) and plaque number (RR = 0.64, 95% CI = 0.52-0.78, Bonferroni corrected p = 4.9*10(-4)). Some interactions with a nominal p<=0.01 were found between sex and SNPs in the UCP1 and UCP3 gene; between smoking, diabetes, hypertension and SNPs in UCP5 and SIRT5; and between SNPs in the UCP5 gene and the UCP1, SIRT1, SIRT3, SIRT5, and SIRT6 genes in association with plaque phenotypes. CONCLUSION: We observed significant associations between genetic variants in the SIRT6 and UCP5 genes and atherosclerotic plaque. We also found potential effect modifications by sex, smoking and vascular risk factors of the SIRT/UCP genes in the associations with atherosclerotic plaque. Further studies are needed to validate our observations. PMID- 22087258 TI - Time-resolved transcriptomics and bioinformatic analyses reveal intrinsic stress responses during batch culture of Bacillus subtilis. AB - We have determined the time-resolved transcriptome of the model gram-positive organism B. subtilis during growth in a batch fermentor on rich medium. DNA microarrays were used to monitor gene transcription using 10-minute intervals at 40 consecutive time points. From the growth curve and analysis of all gene expression levels, we identified 4 distinct growth phases and one clear transition point: a lag phase, an exponential growth phase, the transition point and the very clearly separated early and late stationary growth phases. The gene expression profiles suggest the occurrence of stress responses at specific times although no external stresses were applied. The first one is a small induction of the SigB regulon that occurs at the transition point. Remarkably, a very strong response is observed for the SigW regulon, which is highly upregulated at the onset of the late stationary phase. Bioinformatic analyses that were performed on our data set suggest several novel putative motifs for regulator binding. In addition, the expression profiles of several genes appeared to correlate with the oxygen concentration. This data set of the expression profiles of all B. subtilis genes during the entire growth curve on rich medium constitutes a rich repository that can be further mined by the scientific community. PMID- 22087259 TI - Visualization of the left extraperitoneal space and spatial relationships to its related spaces by the visible human project. AB - BACKGROUND: The major hindrance to multidetector CT imaging of the left extraperitoneal space (LES), and the detailed spatial relationships to its related spaces, is that there is no obvious density difference between them. Traditional gross anatomy and thick-slice sectional anatomy imagery are also insufficient to show the anatomic features of this narrow space in three dimensions (3D). To overcome these obstacles, we used a new method to visualize the anatomic features of the LES and its spatial associations with related spaces, in random sections and in 3D. METHODS: In conjunction with Mimics(r) and Amira(r) software, we used thin-slice cross-sectional images of the upper abdomen, retrieved from the Chinese and American Visible Human dataset and the Chinese Virtual Human dataset, to display anatomic features of the LES and spatial relationships of the LES to its related spaces, especially the gastric bare area. The anatomic location of the LES was presented on 3D sections reconstructed from CVH2 images and CT images. PRINCIPAL FINDINGS: What calls for special attention of our results is the LES consists of the left sub diaphragmatic fat space and gastric bare area. The appearance of the fat pad at the cardiac notch contributes to converting the shape of the anteroexternal surface of the LES from triangular to trapezoidal. Moreover, the LES is adjacent to the lesser omentum and the hepatic bare area in the anterointernal and right rear direction, respectively. CONCLUSION: The LES and its related spaces were imaged in 3D using visualization technique for the first time. This technique is a promising new method for exploring detailed communication relationships among other abdominal spaces, and will promote research on the dynamic extension of abdominal diseases, such as acute pancreatitis and intra-abdominal carcinomatosis. PMID- 22087260 TI - Extracellular matrix ligand and stiffness modulate immature nucleus pulposus cell cell interactions. AB - The nucleus pulposus (NP) of the intervertebral disc functions to provide compressive load support in the spine, and contains cells that play a critical role in the generation and maintenance of this tissue. The NP cell population undergoes significant morphological and phenotypic changes during maturation and aging, transitioning from large, vacuolated immature cells arranged in cell clusters to a sparse population of smaller, isolated chondrocyte-like cells. These morphological and organizational changes appear to correlate with the first signs of degenerative changes within the intervertebral disc. The extracellular matrix of the immature NP is a soft, gelatinous material containing multiple laminin isoforms, features that are unique to the NP relative to other regions of the disc and that change with aging and degeneration. Based on this knowledge, we hypothesized that a soft, laminin-rich extracellular matrix environment would promote NP cell-cell interactions and phenotypes similar to those found in immature NP tissues. NP cells were isolated from porcine intervertebral discs and cultured in matrix environments of varying mechanical stiffness that were functionalized with various matrix ligands; cellular responses to periods of culture were assessed using quantitative measures of cell organization and phenotype. Results show that soft (<720 Pa), laminin-containing extracellular matrix substrates promote NP cell morphologies, cell-cell interactions, and proteoglycan production in vitro, and that this behavior is dependent upon both extracellular matrix ligand and substrate mechanical properties. These findings indicate that NP cell organization and phenotype may be highly sensitive to their surrounding extracellular matrix environment. PMID- 22087261 TI - Mono-(2-ethylhexyl) phthalate directly alters the expression of Leydig cell genes and CYP17 lyase activity in cultured rat fetal testis. AB - Exposure to phthalates in utero alters fetal rat testis gene expression and testosterone production, but much remains to be done to understand the mechanisms underlying the direct action of phthalate within the fetal testis. We aimed to investigate the direct mechanisms of action of mono-(2-ethylhexyl) phthalate (MEHP) on the rat fetal testis, focusing on Leydig cell steroidogenesis in particular. We used an in vitro system based on the culture for three days, with or without MEHP, of rat fetal testes obtained at 14.5 days post-coitum.Exposure to MEHP led to a dose-dependent decrease in testosterone production. Moreover, the production of 5 alpha-dihydrotestosterone (5alpha-DHT) (-68%) and androstenedione (-54%) was also inhibited by 10 uM MEHP, whereas 17 alpha hydroxyprogesterone (17alpha-OHP) production was found to increase (+41%). Testosterone synthesis was rescued by the addition of androstenedione but not by any of the other precursors used. Thus, the hormone data suggested that steroidogenesis was blocked at the level of the 17,20 lyase activity of the P450c17 enzyme (CYP17), converting 17alpha-OHP to androstenedione. The subsequent gene expression and protein levels supported this hypothesis. In addition to Cyp17a1, microarray analysis showed that several other genes important for testes development were affected by MEHP. These genes included those encoding insulin like factor 3 (INSL3), which is involved in controlling testicular descent, and Inha, which encodes the alpha subunit of inhibin B.These findings indicate that under in vitro conditions known to support normal differentiation of the fetal rat testis, the exposure to MEHP directly inhibits several important Leydig cell factors involved in testis function and that the Cyp17a1 gene is a specific target to MEHP explaining the MEHP-induced suppression of steroidogenesis observed. PMID- 22087262 TI - Concurrent HDAC and mTORC1 inhibition attenuate androgen receptor and hypoxia signaling associated with alterations in microRNA expression. AB - Specific inhibitors towards Histone Deacetylases (HDACs) and Mammalian Target of Rapamycin Complex 1 (mTORC1) have been developed and demonstrate potential as treatments for patients with advanced and/or metastatic and castrate resistant prostate cancer (PCa). Further, deregulation of HDAC expression and mTORC1 activity are documented in PCa and provide rational targets to create new therapeutic strategies to treat PCa. Here we report the use of the c-Myc adenocarcinoma cell line from the c-Myc transgenic mouse with prostate cancer to evaluate the in vitro and in vivo anti-tumor activity of the combination of the HDAC inhibitor panobinostat with the mTORC1 inhibitor everolimus. Panobinostat/everolimus combination treatment resulted in significantly greater antitumor activity in mice bearing androgen sensitive Myc-CaP and castrate resistant Myc-CaP tumors compared to single treatments. We identified that panobinostat/everolimus combination resulted in enhanced anti-tumor activity mediated by decreased tumor growth concurrent with augmentation of p21 and p27 expression and the attenuation of angiogenesis and tumor proliferation via androgen receptor, c-Myc and HIF-1alpha signaling. Also, we observed altered expression of microRNAs associated with these three transcription factors. Overall, our results demonstrate that low dose concurrent panobinostat/everolimus combination therapy is well tolerated and results in greater anti-tumor activity compared to single treatments in tumor bearing immuno-competent mice. Finally, our results suggest that response of selected miRs could be utilized to monitor panobinostat/everolimus in vivo activity. PMID- 22087263 TI - Human cumulus cells molecular signature in relation to oocyte nuclear maturity stage. AB - The bi-directional communication between the oocyte and the surrounding cumulus cells (CCs) is crucial for the acquisition of oocyte competence. We investigated the transcriptomic profile of human CCs isolated from mature and immature oocytes under stimulated cycle. We used human Genome U133 Plus 2.0 microarrays to perform an extensive analysis of the genes expressed in human CCs obtained from patients undergoing intra-cytoplasmic sperm injection. CC samples were isolated from oocyte at germinal vesicle, stage metaphase I and stage metaphase II. For microarray analysis, we used eight chips for each CC category. Significance analysis of microarray multiclass was used to analyze the microarray data. Validation was performed by RT-qPCR using an independent cohort of CC samples. We identified differentially over-expressed genes between the three CC categories. This study revealed a specific signature of gene expression in CCs issued from MII oocyte compared with germinal vesicle and metaphase I. The CC gene expression profile, which is specific of MII mature oocyte, can be useful as predictors of oocyte quality. PMID- 22087264 TI - Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap), which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment. PMID- 22087265 TI - Maternal bereavement and childhood asthma-analyses in two large samples of Swedish children. AB - BACKGROUND: Prenatal factors such as prenatal psychological stress might influence the development of childhood asthma. METHODOLOGY AND PRINCIPAL FINDINGS: We assessed the association between maternal bereavement shortly before and during pregnancy, as a proxy for prenatal stress, and the risk of childhood asthma in the offspring, based on two samples of children 1-4 (n = 426,334) and 7 12 (n = 493,813) years assembled from the Swedish Medical Birth Register. Exposure was maternal bereavement of a close relative from one year before pregnancy to child birth. Asthma event was defined by a hospital contact for asthma or at least two dispenses of inhaled corticosteroids or montelukast. In the younger sample we calculated hazards ratios (HRs) of a first-ever asthma event using Cox models and in the older sample odds ratio (ORs) of an asthma attack during 12 months using logistic regression. Compared to unexposed boys, exposed boys seemed to have a weakly higher risk of first-ever asthma event at 1 4 years (HR: 1.09; 95% confidence interval [CI]: 0.98, 1.22) as well as an asthma attack during 12 months at 7-12 years (OR: 1.10; 95% CI: 0.96, 1.24). No association was suggested for girls. Boys exposed during the second trimester had a significantly higher risk of asthma event at 1-4 years (HR: 1.55; 95% CI: 1.19, 2.02) and asthma attack at 7-12 years if the bereavement was an older child (OR: 1.58; 95% CI: 1.11, 2.25). The associations tended to be stronger if the bereavement was due to a traumatic death compared to natural death, but the difference was not statistically significant. CONCLUSIONS/SIGNIFICANCE: Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls. PMID- 22087266 TI - Characterization of visual percepts evoked by noninvasive stimulation of the human posterior parietal cortex. AB - Phosphenes are commonly evoked by transcranial magnetic stimulation (TMS) to study the functional organization, connectivity, and excitability of the human visual brain. For years, phosphenes have been documented only from stimulating early visual areas (V1-V3) and a handful of specialized visual regions (V4, V5/MT+) in occipital cortex. Recently, phosphenes were reported after applying TMS to a region of posterior parietal cortex involved in the top-down modulation of visuo-spatial processing. In the present study, we systematically characterized parietal phosphenes to determine if they are generated directly by local mechanisms or emerge through indirect activation of other visual areas. Using technology developed in-house to record the subjective features of phosphenes, we found no systematic differences in the size, shape, location, or frame-of-reference of parietal phosphenes when compared to their occipital counterparts. In a second experiment, discrete deactivation by 1 Hz repetitive TMS yielded a double dissociation: phosphene thresholds increased at the deactivated site without producing a corresponding change at the non-deactivated location. Overall, the commonalities of parietal and occipital phosphenes, and our ability to independently modulate their excitability thresholds, lead us to conclude that they share a common neural basis that is separate from either of the stimulated regions. PMID- 22087267 TI - Immunogenicity and reactogenicity of 2009 influenza A (H1N1) inactivated monovalent non-adjuvanted vaccine in elderly and immunocompromised patients. AB - BACKGROUND: Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them. METHODS: This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination. RESULTS: 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included. The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events. CONCLUSIONS: The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685). PMID- 22087268 TI - Conformational toggling of yeast iso-1-cytochrome C in the oxidized and reduced states. AB - To convert cyt c into a peroxidase-like metalloenzyme, the P71H mutant was designed to introduce a distal histidine. Unexpectedly, its peroxidase activity was found even lower than that of the native, and that the axial ligation of heme iron was changed to His71/His18 in the oxidized state, while to Met80/His18 in the reduced state, characterized by UV-visible, circular dichroism, and resonance Raman spectroscopy. To further probe the functional importance of Pro71 in oxidation state dependent conformational changes occurred in cyt c, the solution structures of P71H mutant in both oxidation states were determined. The structures indicate that the half molecule of cyt c (aa 50-102) presents a kind of "zigzag riveting ruler" structure, residues at certain positions of this region such as Pro71, Lys73 can move a big distance by altering the tertiary structure while maintaining the secondary structures. This finding provides a molecular insight into conformational toggling in different oxidation states of cyt c that is principle significance to its biological functions in electron transfer and apoptosis. Structural analysis also reveals that Pro71 functions as a key hydrophobic patch in the folding of the polypeptide of the region (aa 50 102), to prevent heme pocket from the solvent. PMID- 22087269 TI - Beta-catenin accelerates human papilloma virus type-16 mediated cervical carcinogenesis in transgenic mice. AB - Human papilloma virus (HPV) is the principal etiological agent of cervical cancer in women, and its DNA is present in virtually all of these tumors. However, exposure to the high-risk HPV types alone is insufficient for tumor development. Identifying specific collaborating factors that will lead to cervical cancer remains an unanswered question, especially because millions of women are exposed to HPV. Our earlier work using an in vitro model indicated that activation of the canonical Wnt pathway in HPV-positive epithelial cells was sufficient to induce anchorage independent growth. We therefore hypothesized that constitutive activation of this pathway might function as the "second hit." To address this possibility, we developed two double-transgenic (DT) mouse models, K14 E7/DeltaN87betacat and K14-HPV16/DeltaN87betacat that express either the proteins encoded by the E7 oncogene or the HPV16 early region along with constitutively active beta-catenin, which was expressed by linking it to the keratin-14 (K14) promoter. We initiated tumor formation by treating all groups with estrogen for six months. Invasive cervical cancer was observed in 11% of the K14 DeltaN87betacat mice, expressing activated beta-catenin and in 50% of the animals expressing the HPV16 E7 oncogene. In double-transgenic mice, coexpression of beta catenin and HPV16 E7 induced invasive cervical cancer at about 7 months in 94% of the cases. We did not observe cervical cancer in any group unless the mice were treated with estrogen. In the second model, K14-HPV16 mice suffered cervical dysplasias, but this phenotype was not augmented in HPV16/DeltaN87betacat mice. In summary, the phenotypes of the K14-E7/DeltaN87betacat mice support the hypothesis that activation of the Wnt/beta-catenin pathway in HPV-associated premalignant lesions plays a functional role in accelerating cervical carcinogenesis. PMID- 22087270 TI - Typologies of prescription opioid use in a large sample of adults assessed for substance abuse treatment. AB - BACKGROUND: As a population, non-medical prescription opioid users are not well defined. We aimed to derive and describe typologies of prescription opioid use and nonmedical use using latent class analysis in an adult population being assessed for substance abuse treatment. METHODS: Latent class analysis was applied to data from 26,314 unique respondents, aged 18-70, self-reporting past month use of a prescription opioid out of a total of 138,928 cases (18.9%) collected by the Addiction Severity Index-Multimedia Version (ASI-MV(r)), a national database for near real-time prescription opioid abuse surveillance. Data were obtained from November 2005 through December 2009. Substance abuse treatment, criminal justice, and public assistance programs in the United States submitted data to the ASI-MV database (n = 538). Six indicators of the latent classes derived from responses to the ASI-MV, a version of the ASI modified to collect prescription opioid abuse and chronic pain experience. The latent class analysis included respondent home ZIP code random effects to account for nesting of respondents within ZIP code. RESULTS: A four-class adjusted latent class model fit best and defined clinically interpretable and relevant subgroups: Use as prescribed, Prescribed misusers, Medically healthy abusers, and Illicit users. Classes varied on key variables, including race/ethnicity, gender, concurrent substance abuse, duration of prescription opioid abuse, mental health problems, and ASI composite scores. Three of the four classes (81% of respondents) exhibited high potential risk for fatal opioid overdose; 18.4% exhibited risk factors for blood-borne infections. CONCLUSIONS: Multiple and distinct profiles of prescription opioid use were detected, suggesting a range of use typologies at differing risk for adverse events. Results may help clinicians and policy makers better focus overdose and blood-borne infection prevention efforts and intervention strategies for prescription opioid abuse reduction. PMID- 22087271 TI - Parental age and lifespan influence offspring recruitment: a long-term study in a seabird. AB - Recent studies of wild populations provide compelling evidence that survival and reproduction decrease with age because of senescence, a decline in functional capacities at old ages. However, in the wild, little is known about effects of parental senescence on offspring quality. We used data from a 21-year study to examine the role of parental age on offspring probability of recruitment in a long-lived bird, the blue-footed booby (Sula nebouxii). Offspring probability of recruiting into the breeding population varied over the life of parents and effects age were similar in mothers and fathers. Offspring recruitment was high when parents were roughly 6-12 years old and low before and after then. Effects of parental age on offspring recruitment varied with lifespan (parental age at last reproduction) and previous breeding experience. Offspring recruitment from young and old parents with long reproductive lifespans was greater than that of offspring from parents with short lifespans at young and old ages. For parents with little previous breeding experience recruitment of offspring decreased with their hatch date, but experienced parents were no similarly affected. We found evidence of terminal effects on offspring recruitment in young parents but not in older parents, suggesting that senescence is more likely a gradual process of deterioration than a process of terminal illness. Failure to recruit probably reflects mortality during the first years after independence but also during the fledgling transition to full independence. Our results show effects of parental age and quality on offspring viability in a long-lived wild vertebrate and support the idea that wild populations are composed of individuals of different quality, and that this individual heterogeneity can influence the dynamics of age structured populations. PMID- 22087272 TI - Detection of human rhinovirus C viral genome in blood among children with severe respiratory infections in the Philippines. AB - Human rhinovirus (HRV) C was recently identified as the third species of HRV using a molecular technique. Infections caused by previously identified HRVs (A and B) are thought to be limited to the respiratory tract; however, pathogenesis of HRVC is still largely unknown. A total of 816 nasopharyngeal swabs from hospitalized children with severe respiratory infections in the Philippines (May 2008-May 2009) were tested for HRV by reverse transcription polymerase chain reaction (RT-PCR), and 243 samples (29.8%) were positive for HRV. Among these patients, serum samples were also tested to determine whether specific HRV species were associated with viremia. Only 30 serum samples (12.3%) were positive for HRV. However, the HRV positive rates were different among HRV species, 3% (4/135) for HRVA, 0% (0/25) for HRVB, and 31% (26/83) for HRVC, and were the highest on 2 days after the onset of symptoms. These results suggest that HRVC may have a different pathogenicity and can more commonly cause viremia than HRVA and HRVB. Serum positive rates for HRV are affected by age, i.e., higher positive rates for those aged 1 year or more. HRVC that were detected from serum exhibited the same level of sequence diversity as those positive only for nasopharyngeal samples in phylogenetic analysis. However, all HRVA which were detected from serum were clustered in a monophyletic clade based on their 5' non-coding region (NCR) sequences, which is closely related with a certain HRVC genotype (A2) in 5' NCR. This finding suggests that the 5'NCR region may be associated with viremia. PMID- 22087273 TI - Characterization of family IV UDG from Aeropyrum pernix and its application in hot-start PCR by family B DNA polymerase. AB - Recombinant uracil-DNA glycosylase (UDG) from Aeropyrum pernix (A. pernix) was expressed in E. coli. The biochemical characteristics of A. pernix UDG (ApeUDG) were studied using oligonucleotides carrying a deoxyuracil (dU) base. The optimal temperature range and pH value for dU removal by ApeUDG were 55-65 degrees C and pH 9.0, respectively. The removal of dU was inhibited by the divalent ions of Zn, Cu, Co, Ni, and Mn, as well as a high concentration of NaCl. The opposite base in the complementary strand affected the dU removal by ApeUDG as follows: U/C~U/G>U/T~U/AP~U/->U/U~U/I>U/A. The phosphorothioate around dU strongly inhibited dU removal by ApeUDG. Based on the above biochemical characteristics and the conservation of amino acid residues, ApeUDG was determined to belong to the IV UDG family. ApeUDG increased the yield of PCR by Pfu DNA polymerase via the removal of dU in amplified DNA. Using the dU-carrying oligonucleotide as an inhibitor and ApeUDG as an activator of Pfu DNA polymerase, the yield of undesired DNA fragments, such as primer-dimer, was significantly decreased, and the yield of the PCR target fragment was increased. This strategy, which aims to amplify the target gene with high specificity and yield, can be applied to all family B DNA polymerases. PMID- 22087274 TI - Reduced polymorphism associated with X chromosome meiotic drive in the stalk-eyed fly Teleopsis dalmanni. AB - Sex chromosome meiotic drive has been suggested as a cause of several evolutionary genetic phenomena, including genomic conflicts that give rise to reproductive isolation between new species. In this paper we present a population genetic analysis of X chromosome drive in the stalk-eyed fly, Teleopsis dalmanni, to determine how this natural polymorphism influences genetic diversity. We analyzed patterns of DNA sequence variation at two X-linked regions (comprising 1325 bp) approximately 50 cM apart and one autosomal region (comprising 921 bp) for 50 males, half of which were collected in the field from one of two allopatric locations and the other half were derived from lab-reared individuals with known brood sex ratios. These two populations are recently diverged but exhibit partial postzygotic reproductive isolation, i.e. crosses produce sterile hybrid males and fertile females. We find no nucleotide or microsatellite variation on the drive X chromosome, whereas the same individuals show levels of variation at autosomal regions that are similar to field-collected flies. Furthermore, one field-caught individual collected 10 years previously had a nearly identical X haplotype to the drive X, and is over 2% divergent from other haplotypes sampled from the field. These results are consistent with a selective sweep that has removed genetic variation from much of the drive X chromosome. We discuss how this finding may relate to the rapid evolution of postzygotic reproductive isolation that has been documented for these flies. PMID- 22087275 TI - On the time course of vocal emotion recognition. AB - How quickly do listeners recognize emotions from a speaker's voice, and does the time course for recognition vary by emotion type? To address these questions, we adapted the auditory gating paradigm to estimate how much vocal information is needed for listeners to categorize five basic emotions (anger, disgust, fear, sadness, happiness) and neutral utterances produced by male and female speakers of English. Semantically-anomalous pseudo-utterances (e.g., The rivix jolled the silling) conveying each emotion were divided into seven gate intervals according to the number of syllables that listeners heard from sentence onset. Participants (n = 48) judged the emotional meaning of stimuli presented at each gate duration interval, in a successive, blocked presentation format. Analyses looked at how recognition of each emotion evolves as an utterance unfolds and estimated the "identification point" for each emotion. Results showed that anger, sadness, fear, and neutral expressions are recognized more accurately at short gate intervals than happiness, and particularly disgust; however, as speech unfolds, recognition of happiness improves significantly towards the end of the utterance (and fear is recognized more accurately than other emotions). When the gate associated with the emotion identification point of each stimulus was calculated, data indicated that fear (M = 517 ms), sadness (M = 576 ms), and neutral (M = 510 ms) expressions were identified from shorter acoustic events than the other emotions. These data reveal differences in the underlying time course for conscious recognition of basic emotions from vocal expressions, which should be accounted for in studies of emotional speech processing. PMID- 22087276 TI - Functional diversification of thylakoidal processing peptidases in Arabidopsis thaliana. AB - Thylakoidal processing peptidase (TPP) is responsible for removing amino-terminal thylakoid-transfer signals from several proteins in the thylakoid lumen. Three TPP isoforms are encoded by the nuclear genome of Arabidopsis thaliana. Previous studies showed that one of them termed plastidic type I signal peptidase 1 (Plsp1) was necessary for processing three thylakoidal proteins and one protein in the chloroplast envelope in vivo. The lack of Plsp1 resulted in seedling lethality, apparently due to disruption of proper thylakoid development. The physiological roles of the other two TPP homologs remain unknown. Here we show that the three A. thaliana TPP isoforms evolved to acquire diverse functions. Phylogenetic analysis revealed that TPP may have originated before the endosymbiotic event, and that there are two groups of TPP in seed plants: one includes Plsp1 and another comprises the other two A. thaliana TPP homologs, which are named as Plsp2A and Plsp2B in this study. The duplication leading to the two groups predates the gymnosperm-angiosperm divergence, and the separation of Plsp2A and Plsp2B occurred after the Malvaceae-Brassicaceae diversification. Quantitative reverse transcription-PCR assay revealed that the two PLSP2 genes were co-expressed in both photosynthetic tissues and roots, whereas the PLSP1 transcript accumulated predominantly in photosynthetic tissues. Both PLSP2 genes were expressed in the aerial parts of the plsp1-null mutant at levels comparable to those in wild-type plants. The seedling-lethal phenotype of the plsp1-null mutant could be rescued by a constitutive expression of Plsp1 cDNA but not by that of Plsp2A or Plsp2B. These results indicate that Plsp1 and Plsp2 evolved to function differently, and that neither of the Plsp2 isoforms is necessary for proper thylakoid development in photosynthetic tissues. PMID- 22087277 TI - Protein characterization of a candidate mechanism SNP for Crohn's disease: the macrophage stimulating protein R689C substitution. AB - High throughput genome wide associations studies (GWAS) are now identifying a large number of genome loci related to risk of common human disease. Each such locus presents a challenge in identifying the relevant underlying mechanism. Here we report the experimental characterization of a proposed causal single nucleotide polymorphism (SNP) in a locus related to risk of Crohn's disease and ulcerative colitis. The SNP lies in the MST1 gene encoding Macrophage Stimulating Protein (MSP), and results in an R689C amino acid substitution within the beta chain of MSP (MSPbeta). MSP binding to the RON receptor tyrosine kinase activates signaling pathways involved in the inflammatory response. We have purified wild type and mutant MSPbeta proteins and compared biochemical and biophysical properties that might impact the MSP/RON signaling pathway. Surface plasmon resonance (SPR) binding studies showed that MSPbeta R689C affinity to RON is approximately 10-fold lower than that of the wild-type MSPbeta and differential scanning fluorimetry (DSF) showed that the thermal stability of the mutant MSPbeta was slightly lower than that of wild-type MSPbeta, by 1.6 K. The substitution was found not to impair the specific Arg483-Val484 peptide bond cleavage by matriptase-1, required for MSP activation, and mass spectrometry of tryptic fragments of the mutated protein showed that the free thiol introduced by the R689C mutation did not form an aberrant disulfide bond. Together, the studies indicate that the missense SNP impairs MSP function by reducing its affinity to RON and perhaps through a secondary effect on in vivo concentration arising from reduced thermodynamic stability, resulting in down-regulation of the MSP/RON signaling pathway. PMID- 22087278 TI - AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. AB - Agonists of GPR40 (FFA1) have been proposed as a means to treat type 2 diabetes. Through lead optimization of a high throughput screening hit, we have identified a novel GPR40 agonist called AMG 837. The objective of these studies was to understand the preclinical pharmacological properties of AMG 837. The activity of AMG 837 on GPR40 was characterized through GTPgammaS binding, inositol phosphate accumulation and Ca(2+) flux assays. Activity of AMG 837 on insulin release was assessed on isolated primary mouse islets. To determine the anti-diabetic activity of AMG 837 in vivo, we tested AMG 837 using a glucose tolerance test in normal Sprague-Dawley rats and obese Zucker fatty rats. AMG 837 was a potent partial agonist in the calcium flux assay on the GPR40 receptor and potentiated glucose stimulated insulin secretion in vitro and in vivo. Acute administration of AMG 837 lowered glucose excursions and increased glucose stimulated insulin secretion during glucose tolerance tests in both normal and Zucker fatty rats. The improvement in glucose excursions persisted following daily dosing of AMG 837 for 21-days in Zucker fatty rats. Preclinical studies demonstrated that AMG 837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels. These studies support the potential utility of AMG 837 for the treatment of type 2 diabetes. PMID- 22087279 TI - Parathyroid hormone-related protein is not required for normal ductal or alveolar development in the post-natal mammary gland. AB - PTHrP is necessary for the formation of the embryonic mammary gland and, in its absence, the embryonic mammary bud fails to form the neonatal duct system. In addition, PTHrP is produced by the breast during lactation and contributes to the regulation of maternal calcium homeostasis during milk production. In this study, we examined the role of PTHrP during post-natal mammary development. Using a PTHrP-lacZ transgenic mouse, we surveyed the expression of PTHrP in the developing post-natal mouse mammary gland. We found that PTHrP expression is restricted to the basal cells of the gland during pubertal development and becomes expressed in milk secreting alveolar cells during pregnancy and lactation. Based on the previous findings that overexpression of PTHrP in cap and myoepithelial cells inhibited ductal elongation during puberty, we predicted that ablation of native PTHrP expression in the post-natal gland would result in accelerated ductal development. To address this hypothesis, we generated two conditional models of PTHrP-deficiency specifically targeted to the postnatal mammary gland. We used the MMTV-Cre transgene to ablate the floxed PTHrP gene in both luminal and myoepithelial cells and a tetracycline-regulated K14-tTA;tetO Cre transgene to target PTHrP expression in just myoepithelial and cap cells. In both models of PTHrP ablation, we found that mammary development proceeds normally despite the absence of PTHrP. We conclude that PTHrP signaling is not required for normal ductal or alveolar development. PMID- 22087280 TI - Monitoring CD27 expression to evaluate Mycobacterium tuberculosis activity in HIV 1 infected individuals in vivo. AB - The level of bacterial activity is only poorly defined during asymptomatic Mycobacterium tuberculosis (MTB) infection. The objective was to study the capacity of a new biomarker, the expression of the T cell maturation marker CD27 on MTB-specific CD4 T cells, to identify active tuberculosis (TB) disease in subjects from a MTB and HIV endemic region. The frequency and CD27 expression of circulating MTB-specific CD4 T cells was determined in 96 study participants after stimulation with purified protein derivative (PPD) using intracellular cytokine staining for IFNgamma (IFNgamma). Subjects were then stratified by their TB and HIV status. Within PPD responders, a CD27(-) phenotype was associated with active TB in HIV(-) (p = 0.0003) and HIV(+) (p = 0.057) subjects, respectively. In addition, loss of CD27 expression preceded development of active TB in one HIV seroconverter. Interestingly, in contrast to HIV(-) subjects, MTB-specific CD4 T cell populations from HIV(+) TB-asymptomatic subjects were often dominated by CD27(-) cells. These data indicate that down-regulation of CD27 on MTB-specific CD4 T cell could be used as a biomarker of active TB, potentially preceding clinical TB disease. Furthermore, these data are consistent with the hypothesis that late, chronic HIV infection is frequently associated with increased mycobacterial activity in vivo. The analysis of T cell maturation and activation markers might thus be a useful tool to monitor TB disease progression. PMID- 22087281 TI - Up-regulation of Th17 cells may underlie inhibition of Treg development caused by immunization with activated syngeneic T cells. AB - BACKGROUND: Our previous work showed that mice immunized with attenuated activated syngeneic T cells (aTCV) led to damping Treg function which resulted in enhancing anti-tumor immunity. It is well known that DC plays a very important role in controlling Th cell differentiation; whether DC involves Treg attenuation in immunized mice remained unknown. In this study, we provided evidence that increased mature DC (mDC) after immunization with aTCV skewed Th17 differentiation, which resulted in inhibition of Treg differentiation through IL 6 signaling pathway. PRINCIPAL FINDINGS: In the present study, we found that the frequency of mDCs increased dramatically in the immunized mice accompanied by lower Treg cells compared to the controls. Moreover, both DCs and serum derived from the immunized mice suppressed Treg differentiation in vitro, respectively. mDCs generated from bone marrow precursor cells in vitro strongly inhibited Treg development and simultaneously drove Th17 differentiation with elevated IL-6 production. However, PD-L1, a potent Treg inducer did not show effect on Treg down-regulation. Assay with transwell systems showed that cell-cell contact was necessary for IL-6 production to a threshold to activate Th17 transcriptional factor RORgammat and to inhibit Treg counterpart Foxp3. CONCLUSIONS: Our results implicate up-regulated Th17 development might be one of mechanisms of enhancing anti-tumor immunity induced by immunization with aTCV, which provide a novel insight in numerous mechanisms responsible for anti-tumor immunity. PMID- 22087283 TI - The proteasome inhibitor bortezomib enhances ATRA-induced differentiation of neuroblastoma cells via the JNK mitogen-activated protein kinase pathway. AB - Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Differentiated human NBs are associated with better outcome and lower stage; induction of differentiation is considered to be therapeutically advantageous. All-trans retinoic acid (ATRA) has been shown to induce the differentiation of neuroblastoma (NB) cell lines. The proteasome inhibitor bortezomib inhibits cell growth and angiogenesis in NBs. Here, we investigated the synergistic effect between bortezomib and ATRA in inducing NB cell differentiation in different NB cell lines. Bortezomib combined with ATRA had a significantly enhanced antiproliferative effect. This inhibition was characterized by a synergistic increase in neuronal differentiation. At the same time, the combination therapy showed little neuronal toxicity which was assessed in primary cultures of rat cerebellar granule cells by the MTT assay, PI staining. The combination of bortezomib and ATRA triggered increased differentiation through the activation of proteins, including RARalpha, RARbeta, RARgamma, p-JNK and p21, compared with ATRA treatment alone. Using JNK inhibitor SP600125 to block JNK-dependent activity, the combination therapy-induced neuronal differentiation was partially attenuated. In addition, p21 shRNA had no effect on the combination therapy induced neuronal differentiation. The in vivo antitumor activities were examined in human NB cell xenografts and GFP-labeled human NB cell xenografts. Treatment of human NB cell CHP126-bearing nude mice with ATRA plus bortezomib resulted in more significant tumor growth inhibition than mice treated with either drug alone. These findings provide the rationale for the development of a new therapeutic strategy for NB based on the pharmacological combination of ATRA and bortezomib. PMID- 22087282 TI - Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging. AB - The amyloid cascade hypothesis provides an economical mechanistic explanation for Alzheimer's disease (AD) dementia and correlated neuropathology. However, some nonagenarian individuals (high pathology controls, HPC) remain cognitively intact while enduring high amyloid plaque loads for decades. If amyloid accumulation is the prime instigator of neurotoxicity and dementia, specific protective mechanisms must enable these HPC to evade cognitive decline. We evaluated the neuropathological and biochemical differences existing between non-demented (ND) HPC and an age-matched cohort with AD dementia. The ND-HPC selected for our study were clinically assessed as ND and possessed high amyloid plaque burdens. ELISA and Western blot analyses were used to quantify a group of proteins related to APP/Abeta/tau metabolism and other neurotrophic and inflammation-related molecules that have been found to be altered in neurodegenerative disorders and are pivotal to brain homeostasis and mental health. The molecules assumed to be critical in AD dementia, such as soluble or insoluble Abeta40, Abeta42 and tau were quantified by ELISA. Interestingly, only Abeta42 demonstrated a significant increase in ND-HPC when compared to the AD group. The vascular amyloid load which was not used in the selection of cases, was on the average almost 2-fold greater in AD than the ND-HPC, suggesting that a higher degree of microvascular dysfunction and perfusion compromise was present in the demented cohort. Neurofibrillary tangles were less frequent in the frontal cortices of ND-HPC. Biochemical findings included elevated vascular endothelial growth factor, apolipoprotein E and the neuroprotective factor S100B in ND-HPC, while anti angiogenic pigment epithelium derived factor levels were lower. The lack of clear Abeta-related pathological/biochemical demarcation between AD and ND-HPC suggests that in addition to amyloid plaques other factors, such as neurofibrillary tangle density and vascular integrity, must play important roles in cognitive failure. PMID- 22087284 TI - Interactions between genetic variants in the adiponectin, adiponectin receptor 1 and environmental factors on the risk of colorectal cancer. AB - BACKGROUND: Metabolic syndrome traits play an important role in the development of colorectal cancer. Adipokines, key metabolic syndrome cellular mediators, when abnormal, may induce carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether polymorphisms of important adipokines, adiponectin (ADIPOQ) and its receptors, either alone or in combination with environmental factors, are implicated in colorectal cancer, a two-stage case-control study was conducted. In the first stage, we evaluated 24 tag single nucleotide polymorphisms (tag SNPs) across ADIPOQ ligand and two ADIPOQ receptors (ADIPOR1 and ADIPOR2) among 470 cases and 458 controls. One SNP with promising association was then analyzed in stage 2 among 314 cases and 355 controls. In our study, ADIPOQ rs1063538 was consistently associated with increased colorectal cancer risk, with an odds ratio (OR) of 1.94 (95%CI: 1.48-2.54) for CC genotype compared with TT genotype. In two factor gene-environment interaction analyses, rs1063538 presented significant interactions with smoking status, family history of cancer and alcohol use, with ORs of 4.52 (95%CI: 2.78-7.34), 3.18 (95%CI: 1.73-5.82) and 1.97 (95%CI: 1.27 3.04) for smokers, individuals with family history of cancer or drinkers with CC genotype compared with non-smokers, individuals without family history of cancer or non-drinkers with TT genotype, respectively. Multifactor gene-environment interactions analysis revealed significant interactions between ADIPOQ rs1063538, ADIPOR1 rs1539355, smoking status and BMI. Individuals carrying one, two and at least three risk factors presented 1.18-fold (95%CI:0.89-fold to 1.58-fold), 1.87 fold (95%CI: 1.38-fold to 2.54-fold) and 4.39-fold (95%CI: 2.75-fold to 7.01 fold) increased colorectal cancer risk compared with those who without risk factor, respectively (P(trend) <0.0001). CONCLUSIONS/SIGNIFICANCE: Our results suggest that variants in ADIPOQ may contribute to increased colorectal cancer risk in Chinese and this contribution may be modified by environmental factors, such as smoking status, family history of cancer and BMI. PMID- 22087285 TI - Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. AB - BACKGROUND: Recent evidence from in vitro and in vivo studies has demonstrated that aberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway regulates genes that promote cellular proliferation in various human cancer stem cells (CSCs). Therefore, the chemotherapeutic agents that inhibit activation of Gli transcription factors have emerged as promising novel therapeutic drugs for pancreatic cancer. GDC-0449 (Vismodegib), orally administrable molecule belonging to the 2-arylpyridine class, inhibits SHH signaling pathway by blocking the activities of Smoothened. The objectives of this study were to examine the molecular mechanisms by which GDC-0449 regulates human pancreatic CSC characteristics in vitro. METHODOLOGY/PRINCIPAL FINDINGS: GDC-0499 inhibited cell viability and induced apoptosis in three pancreatic cancer cell lines and pancreatic CSCs. This inhibitor also suppressed cell viability, Gli-DNA binding and transcriptional activities, and induced apoptosis through caspase-3 activation and PARP cleavage in pancreatic CSCs. GDC-0449-induced apoptosis in CSCs showed increased Fas expression and decreased expression of PDGFRalpha. Furthermore, Bcl-2 was down-regulated whereas TRAIL-R1/DR4 and TRAIL-R2/DR5 expression was increased following the treatment of CSCs with GDC-0449. Suppression of both Gli1 plus Gli2 by shRNA mimicked the changes in cell viability, spheroid formation, apoptosis and gene expression observed in GDC-0449 treated pancreatic CSCs. Thus, activated Gli genes repress DRs and Fas expressions, up-regulate the expressions of Bcl-2 and PDGFRalpha and facilitate cell survival. CONCLUSIONS/SIGNIFICANCE: These data suggest that GDC-0499 can be used for the management of pancreatic cancer by targeting pancreatic CSCs. PMID- 22087286 TI - Comparative proteomic approach identifies PKM2 and cofilin-1 as potential diagnostic, prognostic and therapeutic targets for pulmonary adenocarcinoma. AB - Lung cancer is the leading cause of cancer-related death in the world. Non-small cell lung carcinomas (Non-SCLC) account for almost 80% of lung cancers, of which 40% were adenocarcinomas. For a better understanding of the molecular mechanisms behind the development and progression of lung cancer, particularly lung adenocarcinoma, we have used proteomics technology to search for candidate prognostic and therapeutic targets in pulmonary adenocarcinoma. The protein profile changes between human pulmonary adenocarcinoma tissue and paired surrounding normal tissue were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-DE) based approach. Differentially expressed protein-spots were identified with ESI-Q-TOF MS/MS instruments. As a result, thirty two differentially expressed proteins (over 2-fold, p<0.05) were identified in pulmonary adenocarcinoma compared to normal tissues. Among them, two proteins (PKM2 and cofilin-1), significantly up-regulated in adenocarcinoma, were selected for detailed analysis. Immunohistochemical examination indicated that enhanced expression of PKM2 and cofilin-1 were correlated with the severity of epithelial dysplasia, as well as a relatively poor prognosis. Knockdown of PKM2 expression by RNA interference led to a significant suppression of cell growth and induction of apoptosis in pulmonary adenocarcinoma SPC-A1 cells in vitro, and tumor growth inhibition in vivo xenograft model (P<0.05). In addition, the shRNA expressing plasmid targeting cofilin-1 significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. While additional works are needed to elucidate the biological significance and molecular mechanisms of these altered proteins identified in this study, PKM2 and cofilin-1 may serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets for pulmonary adenocarcinoma. PMID- 22087287 TI - Involvement of FOXO transcription factors, TRAIL-FasL/Fas, and sirtuin proteins family in canine coronavirus type II-induced apoptosis. AB - n our previous study, we have shown that canine coronavirus type II (CCoV-II) activates both extrinsic and intrinsic apoptotic pathway in a canine fibrosarcoma cell line (A-72 cells). Herein we investigated the role of Sirtuin and Forkhead box O (FOXO) families in this experimental model using Nortern Blot and Western Blot analysis. Our results demonstrated that mitochondrial SIRT3 and SIRT4 protein expression increased from 12 and 24 h post infection (p.i.) onwards, respectively, whereas the nuclear SIRT1 expression increased during the first 12 h p.i. followed by a decrease after 36 h p.i., reaching the same level of control at 48 h p.i. Sirtuins interact with/and regulate the activity of FOXO family proteins, and we herein observed that FOXO3A and FOXO1 expression increased significantly and stably from 12 h p.i. onwards. In addition, CCoV-II induces a remarkable increase in the expression of TNF-related apoptosis-inducing ligand (TRAIL), while we observed a slight up-regulation of FasL/Fas at 36 p.i. with a decrease of both proteins at the end of infection. Furthermore, we found that virus infection increased both bax translocation into mitochondria and decreased bcl-2 expression in cytosol in a time-dependent manner.These data suggest that FOXO transcription factors mediate pro-apoptotic effects of CCoV-II, in part due to activation of extrinsic apoptosis pathway, while some Sirtuin family members (such as SIRT3 and SIRT4) may be involved in intrinsic apoptotic pathway. Moreover, these results propose that TRAIL is an important mediator of cell death induced by CCoV-II during in vitro infection. PMID- 22087288 TI - A novel validation algorithm allows for automated cell tracking and the extraction of biologically meaningful parameters. AB - Automated microscopy is currently the only method to non-invasively and label free observe complex multi-cellular processes, such as cell migration, cell cycle, and cell differentiation. Extracting biological information from a time series of micrographs requires each cell to be recognized and followed through sequential microscopic snapshots. Although recent attempts to automatize this process resulted in ever improving cell detection rates, manual identification of identical cells is still the most reliable technique. However, its tedious and subjective nature prevented tracking from becoming a standardized tool for the investigation of cell cultures. Here, we present a novel method to accomplish automated cell tracking with a reliability comparable to manual tracking. Previously, automated cell tracking could not rival the reliability of manual tracking because, in contrast to the human way of solving this task, none of the algorithms had an independent quality control mechanism; they missed validation. Thus, instead of trying to improve the cell detection or tracking rates, we proceeded from the idea to automatically inspect the tracking results and accept only those of high trustworthiness, while rejecting all other results. This validation algorithm works independently of the quality of cell detection and tracking through a systematic search for tracking errors. It is based only on very general assumptions about the spatiotemporal contiguity of cell paths. While traditional tracking often aims to yield genealogic information about single cells, the natural outcome of a validated cell tracking algorithm turns out to be a set of complete, but often unconnected cell paths, i.e. records of cells from mitosis to mitosis. This is a consequence of the fact that the validation algorithm takes complete paths as the unit of rejection/acceptance. The resulting set of complete paths can be used to automatically extract important biological parameters with high reliability and statistical significance. These include the distribution of life/cycle times and cell areas, as well as of the symmetry of cell divisions and motion analyses. The new algorithm thus allows for the quantification and parameterization of cell culture with unprecedented accuracy. To evaluate our validation algorithm, two large reference data sets were manually created. These data sets comprise more than 320,000 unstained adult pancreatic stem cells from rat, including 2592 mitotic events. The reference data sets specify every cell position and shape, and assign each cell to the correct branch of its genealogic tree. We provide these reference data sets for free use by others as a benchmark for the future improvement of automated tracking methods. PMID- 22087289 TI - The antiangiogenic 16K prolactin impairs functional tumor neovascularization by inhibiting vessel maturation. AB - BACKGROUND: Angiogenesis, the formation of new blood vessels from existing vasculature, plays an essential role in tumor growth, invasion, and metastasis. 16K hPRL, the antiangiogenic 16-kDa N-terminal fragment of human prolactin was shown to prevent tumor growth and metastasis by modifying tumor vessel morphology. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effect of 16K hPRL on tumor vessel maturation and on the related signaling pathways. We show that 16K hPRL treatment leads, in a murine B16-F10 tumor model, to a dysfunctional tumor vasculature with reduced pericyte coverage, and disruption of the PDGF-B/PDGFR-B, Ang/Tie2, and Delta/Notch pathways. In an aortic ring assay, 16K hPRL impairs endothelial cell and pericyte outgrowth from the vascular ring. In addition, 16K hPRL prevents pericyte migration to endothelial cells. This event was independent of a direct inhibitory effect of 16K hPRL on pericyte viability, proliferation, or migration. In endothelial cell-pericyte cocultures, we found 16K hPRL to disturb Notch signaling. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show that 16K hPRL impairs functional tumor neovascularization by inhibiting vessel maturation and for the first time that an endogenous antiangiogenic agent disturbs Notch signaling. These findings provide new insights into the mechanisms of 16K hPRL action and highlight its potential for use in anticancer therapy. PMID- 22087290 TI - Displacement of the predominant dengue virus from type 2 to type 1 with a subsequent genotype shift from IV to I in Surabaya, Indonesia 2008-2010. AB - Indonesia has annually experienced approximately 100,000 reported cases of dengue fever (DF) and dengue hemorrhagic fever (DHF) in recent years. However, epidemiological surveys of dengue viruses (DENVs) have been limited in this country. In Surabaya, the second largest city, a single report indicated that dengue virus type 2 (DENV2) was the predominant circulating virus in 2003-2005. We conducted three surveys in Surabaya during: (i) April 2007, (ii) June 2008 to April 2009, and (iii) September 2009 to December 2010. A total of 231 isolates were obtained from dengue patients and examined by PCR typing. We found that the predominant DENV shifted from type 2 to type 1 between October and November 2008. Another survey using wild-caught mosquitoes in April 2009 confirmed that dengue type 1 virus (DENV1) was the predominant type in Surabaya. Phylogenetic analyses of the nucleotide sequences of the complete envelope gene of DENV1 indicated that all 22 selected isolates in the second survey belonged to genotype IV and all 17 selected isolates in the third survey belonged to genotype I, indicating a genotype shift between April and September 2009. Furthermore, in December 2010, isolates were grouped into a new clade of DENV1 genotype I, suggesting clade shift between September and December 2010. According to statistics reported by the Surabaya Health Office, the proportion of DHF cases among the total number of dengue cases increased about three times after the type shift in 2008. In addition, the subsequent genotype shift in 2009 was associated with the increased number of total dengue cases. This indicates the need for continuous surveillance of circulating viruses to predict the risk of DHF and DF. PMID- 22087291 TI - Twist controls skeletal development and dorsoventral patterning by regulating runx2 in zebrafish. AB - BACKGROUND: Twist1a and twist1b are the principal components of twists that negatively regulate a number of cellular signaling events. Expression of runx2 and downstream targets is essential for skeletal development and ventral organizer formation and specification in early vertebrate embryos, but what controls ventral activity of maternal runx2 and how twists function in zebrafish embryogenesis still remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: By studying the loss of twist induced by injection of morpholino-oligonucleotide in zebrafish, we found that twist1a and twist1b, but not twist2 or twist3, were required for proper skeletal development and dorsoventral patterning in early embryos. Overexpression of twist1a or twist1b following mRNA injection resulted in deteriorated skeletal development and formation of typical dorsalized embryos, whereas knockdown of twist1a and twist1b led to the formation of abnormal embryos with enhanced skeletal formation and typical ventralized patterning. Overexpression of twist1a or twist1b decreased the expression of runx2b, whereas twist1a and twist1b knockdown increased runx2b expression. We have further demonstrated that phenotypes induced by twist1a and twist1b knockdown were rescued by runx2b knockdown. CONCLUSIONS/SIGNIFICANCE: Together, these results suggest that twist1a and twist1b control skeletal development and dorsoventral patterning by regulating runx2b in zebrafish and provide potential targets for the treatment of diseases or syndromes associated with decreased skeletal development. PMID- 22087293 TI - Fish consumption measured during pregnancy and risk of cardiovascular diseases later in life: an observational prospective study. AB - Previous studies have indicated a protective effect of long chain n-3 PUFAs against cardiovascular disease; however, the overall evidence remains uncertain, and there is a general lack of knowledge in the field of cardiovascular epidemiology in women. Therefore, the objective of this study was to explore the association between fish intake and cardiovascular disease among 7429 women from a prospective pregnancy cohort in Aarhus, Denmark, who were followed for 12-17 years. Exposure information derived from a questionnaire sent to the women in gestation week 16, and daily fish consumption was quantified based on assumptions of standard portion sizes and food tables. Information on admissions to hospital was obtained from the Danish National Patient Registry and diagnoses of hypertensive, cerebrovascular and ischaemic heart disease were used to define the outcome: cardiovascular disease. During the follow-up period 263 events of cardiovascular disease were identified. Overall, there was no association between cardiovascular disease and fish intake, confidence intervals for effect estimates in the different fish intake groups were wide, overlapped and for all but one they encompassed unity. Restricting the analysis to women who had reported the same fish intake in a questionnaire in gestation week 30 did not alter these findings. In conclusion, our data from a prospective cohort of relatively young and initially healthy women from Aarhus linked with information from registries could not substantiate a protective effect of fish intake against cardiovascular disease. PMID- 22087292 TI - Bivariate genome-wide association analyses of femoral neck bone geometry and appendicular lean mass. AB - OBJECTIVE: Femoral neck geometric parameters (FNGPs), such as periosteal diameter (W), cross-sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are highly genetically correlated with body lean mass. However, the specific SNPs/genes shared by these phenotypes are largely unknown. METHODS: To identify the specific SNPs/genes shared between FNGPs and appendicular lean mass (ALM), we performed an initial bivariate genome-wide association study (GWAS) by scanning ~690,000 SNPs in 1,627 unrelated Han Chinese adults (802 males and 825 females) and a follow-up replicate study in 2,286 unrelated US Caucasians. RESULTS: We identified 13 interesting SNPs that may be important for both FNGPs and ALM. Two SNPs, rs681900 located in the HK2 (hexokinase 2) gene and rs11859916 in the UMOD (uromodulin) gene, were bivariately associated with FNGPs and ALM (p = 7.58*10(-6) for ALM-BR and p = 2.93*10(-6) for ALM-W, respectively). The associations were then replicated in Caucasians, with corresponding p values of 0.024 for rs681900 and 0.047 for rs11859916. Meta-analyses yielded combined p values of 3.05*10(-6) and 2.31*10( 6) for rs681900 and rs11859916, respectively. Our findings are consistent with previous biological studies that implicated HK2 and UMOD in both FNGPs and ALM. Our study also identified a group of 11 contiguous SNPs, which spanned a region of ~130 kb, were bivariately associated with FNGPs and ALM, with p values ranging from 3.06*10(-7) to 4.60*10(-6) for ALM-BR. The region contained two neighboring miRNA coding genes, MIR873 (MicroRNA873) and MIR876 (MicroRNA876). CONCLUSION: Our study implicated HK2, UMOD, MIR873 and MIR876, as pleiotropic genes underlying variation of both FNGPs and ALM, thus suggesting their important functional roles in co-regulating both FNGPs and ALM. PMID- 22087294 TI - Relative changes in krill abundance inferred from Antarctic fur seal. AB - Antarctic krill Euphausia superba is a predominant species in the Southern Ocean, it is very sensitive to climate change, and it supports large stocks of fishes, seabirds, seals and whales in Antarctic marine ecosystems. Modern krill stocks have been estimated directly by net hauls and acoustic surveys; the historical krill density especially the long-term one in the Southern Ocean, however, is unknown. Here we inferred the relative krill population changes along the West Antarctic Peninsula (WAP) over the 20th century from the trophic level change of Antarctic fur seal Arctocephalus gazella using stable carbon (delta(13)C) and nitrogen (delta(15)N) isotopes of archival seal hairs. Since Antarctic fur seals feed preferentially on krill, the variation of delta(15)N in seal hair indicates a change in the proportion of krill in the seal's diets and thus the krill availability in local seawater. For the past century, enriching fur seal delta(15)N values indicated decreasing krill availability. This is agreement with direct observation for the past ~30 years and suggests that the recently documented decline in krill populations began in the early parts of the 20th century. This novel method makes it possible to infer past krill population changes from ancient tissues of krill predators. PMID- 22087295 TI - Expression of the neuregulin receptor ErbB4 in the brain of the rhesus monkey (Macaca mulatta). AB - We demonstrated recently that frontal cortical expression of the Neuregulin (NRG) receptor ErbB4 is restricted to interneurons in rodents, macaques, and humans. However, little is known about protein expression patterns in other areas of the brain. In situ hybridization studies have shown high ErbB4 mRNA levels in various subcortical areas, suggesting that ErbB4 is also expressed in cell types other than cortical interneurons. Here, using highly-specific monoclonal antibodies, we provide the first extensive report of ErbB4 protein expression throughout the cerebrum of primates. We show that ErbB4 immunoreactivity is high in association cortices, intermediate in sensory cortices, and relatively low in motor cortices. The overall immunoreactivity in the hippocampal formation is intermediate, but is high in a subset of interneurons. We detected the highest overall immunoreactivity in distinct locations of the ventral hypothalamus, medial habenula, intercalated nuclei of the amygdala and structures of the ventral forebrain, such as the islands of Calleja, olfactory tubercle and ventral pallidum, and medium expression in the reticular thalamic nucleus. While this pattern is generally consistent with ErbB4 mRNA expression data, further investigations are needed to identify the exact cellular and subcellular sources of mRNA and protein expression in these areas. In contrast to in situ hybridization in rodents, we detected only low levels of ErbB4-immunoreactivity in mesencephalic dopaminergic nuclei but a diffuse pattern of immunofluorescence that was medium in the dorsal striatum and high in the ventral forebrain, suggesting that most ErbB4 protein in dopaminergic neurons could be transported to axons. We conclude that the NRG-ErbB4 signaling pathway can potentially influence many functional systems throughout the brain of primates, and suggest that major sites of action are areas of the "corticolimbic" network. This interpretation is functionally consistent with the genetic association of NRG1 and ERBB4 with schizophrenia. PMID- 22087296 TI - A map of copy number variations in Chinese populations. AB - It has been shown that the human genome contains extensive copy number variations (CNVs). Investigating the medical and evolutionary impacts of CNVs requires the knowledge of locations, sizes and frequency distribution of them within and between populations. However, CNV study of Chinese minorities, which harbor the majority of genetic diversity of Chinese populations, has been underrepresented considering the same efforts in other populations. Here we constructed, to our knowledge, a first CNV map in seven Chinese populations representing the major linguistic groups in China with 1,440 CNV regions identified using Affymetrix SNP 6.0 Array. Considerable differences in distributions of CNV regions between populations and substantial population structures were observed. We showed that ~35% of CNV regions identified in minority ethnic groups are not shared by Han Chinese population, indicating that the contribution of the minorities to genetic architecture of Chinese population could not be ignored. We further identified highly differentiated CNV regions between populations. For example, a common deletion in Dong and Zhuang (44.4% and 50%), which overlaps two keratin associated protein genes contributing to the structure of hair fibers, was not observed in Han Chinese. Interestingly, the most differentiated CNV deletion between HapMap CEU and YRI containing CCL3L1 gene reported in previous studies was also the highest differentiated regions between Tibetan and other populations. Besides, by jointly analyzing CNVs and SNPs, we found a CNV region containing gene CTDSPL were in almost perfect linkage disequilibrium between flanking SNPs in Tibetan while not in other populations except HapMap CHD. Furthermore, we found the SNP taggability of CNVs in Chinese populations was much lower than that in European populations. Our results suggest the necessity of a full characterization of CNVs in Chinese populations, and the CNV map we constructed serves as a useful resource in further evolutionary and medical studies. PMID- 22087297 TI - The epigenetic modifier PRDM5 functions as a tumor suppressor through modulating WNT/beta-catenin signaling and is frequently silenced in multiple tumors. AB - BACKGROUND: PRDM (PRDI-BF1 and RIZ domain containing) proteins are zinc finger proteins involved in multiple cellular regulations by acting as epigenetic modifiers. We studied a recently identified PRDM member PRDM5 for its epigenetic abnormality and tumor suppressive functions in multiple tumorigeneses. METHODOLOGY/PRINCIPAL FINDINGS: Semi-quantitative RT-PCR showed that PRDM5 was broadly expressed in human normal tissues, but frequently silenced or downregulated in multiple carcinoma cell lines due to promoter CpG methylation, including 80% (4/5) nasopharyngeal, 44% (8/18) esophageal, 76% (13/17) gastric, 50% (2/4) cervical, and 25% (3/12) hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell lines. PRDM5 expression could be restored by 5-aza-2'-deoxycytidine demethylation treatment in silenced cell lines. PRDM5 methylation was frequently detected by methylation-specific PCR (MSP) in multiple primary tumors, including 93% (43/46) nasopharyngeal, 58% (25/43) esophageal, 88% (37/42) gastric and 63% (29/46) hepatocellular tumors. PRDM5 was further found a stress-responsive gene, but its response was impaired when the promoter was methylated. Ectopic PRDM5 expression significantly inhibited tumor cell clonogenicity, accompanied by the inhibition of TCF/beta catenin-dependent transcription and downregulation of CDK4, TWIST1 and MDM2 oncogenes, while knocking down of PRDM5 expression lead to increased cell proliferation. ChIP assay showed that PRDM5 bound to its target gene promoters and suppressed their transcription. An inverse correlation between the expression of PRDM5 and activated beta-catenin was also observed in cell lines. CONCLUSIONS/SIGNIFICANCE: PRDM5 functions as a tumor suppressor at least partially through antagonizing aberrant WNT/beta-catenin signaling and oncogene expression. Frequent epigenetic silencing of PRDM5 is involved in multiple tumorigeneses, which could serve as a tumor biomarker. PMID- 22087298 TI - Association study on IL4, IL13 and IL4RA polymorphisms in mite-sensitized persistent allergic rhinitis in a Chinese population. AB - BACKGROUND: The IL4, IL13, and IL4 receptor alpha chain (IL4RA) genes are candidate genes for atopic diseases. We hypothesized that the polymorphisms in these genes are associated with persistent allergic rhinitis (PER). OBJECTIVE: To investigate the association of the potential functional polymorphisms in IL4, IL13, and IL4RA with PER induced by house dust mites in a Chinese population. METHODS: Using the TaqMan method, we genotyped six single nucleotide polymorphisms (SNPs) including C-590T in IL4, C-1055T and Arg130Gln in IL13, and Ile50Val, Ser478Pro and Gln551Arg in IL4RA, in a case-control study of 265 patients with PER and 275 healthy controls. RESULTS: We found that the CT/CC genotypes in IL4 C-590T were associated with a significantly decreased risk of mite-sensitized PER [adjusted odds ratio (OR) = 0.64, 95% confidence interval (CI) 0.45-0.92], compared to the TT genotype. Furthermore, PER patients with CT/CC genotypes had significantly lower serum levels of total IgE than those with TT genotype (P = 0.001). However, there was no significant association of the IL13 and IL4RA polymorphisms with mite-sensitized PER (P>0.05). CONCLUSIONS: Our results suggest that the C-590T polymorphism in IL4 may contribute to the susceptibility to mite-sensitized PER in a Chinese population. PMID- 22087299 TI - Outcomes of patients with benign liver diseases undergoing living donor versus deceased donor liver transplantation. AB - BACKGROUND/AIMS: The number of people undergoing living donor liver transplantation (LDLT) has increased rapidly in many transplant centres. Patients considering LDLT need to know whether LDLT is riskier than deceased donor liver transplantation (DDLT). The aim of this study was to compare the outcomes of patients undergoing LDLT versus DDLT. METHODS: A total of 349 patients with benign liver diseases were recruited from 2005 to 2011 for this study. LDLT was performed in 128 patients, and DDLT was performed in 221 patients. Pre- and intra operative variables for the two groups were compared. Statistically analysed post operative outcomes include the postoperative incidence of complication, biliary and vascular complication, hepatitis B virus (HBV) recurrence, long-term survival rate and outcomes of emergency transplantation. RESULTS: The waiting times were 22.10+/-15.31 days for the patients undergoing LDLT versus 35.81+/-29.18 days for the patients undergoing DDLT. The cold ischemia time (CIT) was 119.34+/-19.75 minutes for the LDLT group and 346+/-154.18 for DDLT group. LDLT group had higher intraoperative blood loss, but red blood cell (RBC) transfusion was not different. Similar >= Clavien III complications, vascular complications, hepatitis B virus (HBV) recurrence and long-term survival rates were noted. LDLT patients suffered a higher incidence of biliary complications in the early postoperative days. However, during the long-term follow-up period, biliary complication rates were similar between the two groups. The long-term survival rate of patients undergoing emergency transplantation was lower than of patients undergoing elective transplantation. However, no significant difference was observed between emergency LDLT and emergency DDLT. CONCLUSIONS: Patients undergoing LDLT achieved similar outcomes to patients undergoing DDLT. Although LDLT patients may suffer a higher incidence of early biliary complications, the total biliary complication rate was similar during the long-term follow-up period. PMID- 22087300 TI - Marine reptiles. PMID- 22087301 TI - Energy beyond food: foraging theory informs time spent in thermals by a large soaring bird. AB - Current understanding of how animals search for and exploit food resources is based on microeconomic models. Although widely used to examine feeding, such constructs should inform other energy-harvesting situations where theoretical assumptions are met. In fact, some animals extract non-food forms of energy from the environment, such as birds that soar in updraughts. This study examined whether the gains in potential energy (altitude) followed efficiency-maximising predictions in the world's heaviest soaring bird, the Andean condor (Vultur gryphus). Animal-attached technology was used to record condor flight paths in three-dimensions. Tracks showed that time spent in patchy thermals was broadly consistent with a strategy to maximise the rate of potential energy gain. However, the rate of climb just prior to leaving a thermal increased with thermal strength and exit altitude. This suggests higher rates of energetic gain may not be advantageous where the resulting gain in altitude would lead to a reduction in the ability to search the ground for food. Consequently, soaring behaviour appeared to be modulated by the need to reconcile differing potential energy and food energy distributions. We suggest that foraging constructs may provide insight into the exploitation of non-food energy forms, and that non-food energy distributions may be more important in informing patterns of movement and residency over a range of scales than previously considered. PMID- 22087302 TI - Shared and unique patterns of embryo development in extremophile poeciliids. AB - BACKGROUND: Closely related lineages of livebearing fishes have independently adapted to two extreme environmental factors: toxic hydrogen sulphide (H(2)S) and perpetual darkness. Previous work has demonstrated in adult specimens that fish from these extreme habitats convergently evolved drastically increased head and offspring size, while cave fish are further characterized by reduced pigmentation and eye size. Here, we traced the development of these (and other) divergent traits in embryos of Poecilia mexicana from benign surface habitats ("surface mollies") and a sulphidic cave ("cave mollies"), as well as in embryos of the sister taxon, Poecilia sulphuraria from a sulphidic surface spring ("sulphur mollies"). We asked at which points during development changes in the timing of the involved processes (i.e., heterochrony) would be detectible. METHODS AND RESULTS: Data were extracted from digital photographs taken of representative embryos for each stage of development and each type of molly. Embryo mass decreased in convergent fashion, but we found patterns of embryonic fat content and ovum/embryo diameter to be divergent among all three types of mollies. The intensity of yellow colouration of the yolk (a proxy for carotenoid content) was significantly lower in cave mollies throughout development. Moreover, while relative head size decreased through development in surface mollies, it increased in both types of extremophile mollies, and eye growth was arrested in mid-stage embryos of cave mollies but not in surface or sulphur mollies. CONCLUSION: Our results clearly demonstrate that even among sister taxa convergence in phenotypic traits is not always achieved by the same processes during embryo development. Furthermore, teleost development is crucially dependent on sufficient carotenoid stores in the yolk, and so we discuss how the apparent ability of cave mollies to overcome this carotenoid-dependency may represent another potential mechanism explaining the lack of gene flow between surface and cave mollies. PMID- 22087303 TI - Identifying temporal codes in spontaneously active sensory neurons. AB - The manner in which information is encoded in neural signals is a major issue in Neuroscience. A common distinction is between rate codes, where information in neural responses is encoded as the number of spikes within a specified time frame (encoding window), and temporal codes, where the position of spikes within the encoding window carries some or all of the information about the stimulus. One test for the existence of a temporal code in neural responses is to add artificial time jitter to each spike in the response, and then assess whether or not information in the response has been degraded. If so, temporal encoding might be inferred, on the assumption that the jitter is small enough to alter the position, but not the number, of spikes within the encoding window. Here, the effects of artificial jitter on various spike train and information metrics were derived analytically, and this theory was validated using data from afferent neurons of the turtle vestibular and paddlefish electrosensory systems, and from model neurons. We demonstrate that the jitter procedure will degrade information content even when coding is known to be entirely by rate. For this and additional reasons, we conclude that the jitter procedure by itself is not sufficient to establish the presence of a temporal code. PMID- 22087304 TI - Astrocyte-secreted factors modulate a gradient of primary dendritic arbors in nucleus laminaris of the avian auditory brainstem. AB - Neurons in nucleus laminaris (NL) receive binaural, tonotopically matched input from nucleus magnocelluaris (NM) onto bitufted dendrites that display a gradient of dendritic arbor size. These features improve computation of interaural time differences, which are used to determine the locations of sound sources. The dendritic gradient emerges following a period of significant reorganization at embryonic day 15 (E15), which coincides with the emergence of astrocytes that express glial fibrillary acidic protein (GFAP) in the auditory brainstem. The major changes include a loss of total dendritic length, a systematic loss of primary dendrites along the tonotopic axis, and lengthening of primary dendrites on caudolateral NL neurons. Here we have tested whether astrocyte-derived molecules contribute to these changes in dendritic morphology. We used an organotypic brainstem slice preparation to perform repeated imaging of individual dye-filled NL neurons to determine the effects of astrocyte-conditioned medium (ACM) on dendritic morphology. We found that treatment with ACM induced a decrease in the number of primary dendrites in a tonotopically graded manner similar to that observed during normal development. Our data introduce a new interaction between astrocytes and neurons in the auditory brainstem and suggest that these astrocytes influence multiple aspects of auditory brainstem maturation. PMID- 22087305 TI - BDNF polymorphism predicts general intelligence after penetrating traumatic brain injury. AB - Neuronal plasticity is a fundamental factor in cognitive outcome following traumatic brain injury. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in this process. While there are many ways to measure cognitive outcome, general cognitive intelligence is a strong predictor of everyday decision-making, occupational attainment, social mobility and job performance. Thus it is an excellent measure of cognitive outcome following traumatic brain injury (TBI). Although the importance of the single-nucleotide polymorphisms polymorphism on cognitive function has been previously addressed, its role in recovery of general intelligence following TBI is unknown. We genotyped male Caucasian Vietnam combat veterans with focal penetrating TBI (pTBI) (n = 109) and non-head injured controls (n = 38) for 7 BDNF single-nucleotide polymorphisms. Subjects were administrated the Armed Forces Qualification Test (AFQT) at three different time periods: pre-injury on induction into the military, Phase II (10-15 years post-injury, and Phase III (30 35 years post-injury). Two single-nucleotide polymorphisms, rs7124442 and rs1519480, were significantly associated with post-injury recovery of general cognitive intelligence with the most pronounced effect at the Phase II time point, indicating lesion-induced plasticity. The genotypes accounted for 5% of the variance of the AFQT scores, independently of other significant predictors such as pre-injury intelligence and percentage of brain volume loss. These data indicate that genetic variations in BDNF play a significant role in lesion induced recovery following pTBI. Identifying the underlying mechanism of this brain-derived neurotrophic factor effect could provide insight into an important aspect of post-traumatic cognitive recovery. PMID- 22087306 TI - Are Helicobacter pylori and other Helicobacter species infection associated with human biliary lithiasis? A meta-analysis. AB - BACKGROUND: Since the isolation of Helicobacter species in biliary system, a hypothetical question was raised about the role of these agents in the development of cholelithiasis. This meta-analysis is to explore the association between the Helicobacter infection and biliary lithiasis. METHODOLOGY/PRINCIPAL FINDINGS: A systematic literature search was performed to identify all eligible articles. Meta-analysis which was carried out using odds ratio and random effect model, 95% confidence intervals for odds ratio was calculated. Quantitative assessment of heterogeneity was explored by chi-square test with significance set at P value 0.10 and was measured using I(2) statistic. Eighteen studies published between 1998 and 2011 were finally eligible for meta-analysis. H. pylori, H. bilis, H. hepaticus, H. pullorum and H. ganmani were studied. With heterogeneity (I(2) = 69.5%, P<0.0001), significantly higher pooled infection rates of H. pylori (OR: 2.59, 35.82% versus 26.75%, P = 0.01) and H. hepaticus (OR: 3.13, 31.30% versus 12.12%, P = 0.02) were observed in lithiasis group. Higher prevalence of H. pylori in cholelithiasis patients were reported by studies from East Asia, South Asia and South America. Evidences supporting the higher presence of H. pylori in cholelithiasis patients could be found by PCR for detecting 16s rRNA in bile, 26 kDa protein gene in biliary tissue and immunohistochemistry. Using multiple detection tests could increase the detection rate of H. pylori. CONCLUSIONS/SIGNIFICANCES: Our meta-analysis suggests a trend of higher presence of H. pylori in cholelithiasis patients than control group and this trend was significant in the regions with higher prevalence of this agent. Evidences supporting the association between Helicobacter and cholelithiasis could be found by using different tests but the gold standard for the identification of these bacteria in biliary system has yet to be established. Considering obvious heterogeneity, a large multi-center study will facilitate us to further clarify the association between the Helicobacter infection and cholelithiasis. PMID- 22087307 TI - CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain. AB - The "Function to Find Domain" (FIIND)-containing proteins CARD8 (Cardinal; Tucan) and NLRP1 (NALP1; NAC) are well known components of inflammasomes, multiprotein complexes responsible for activation of caspase-1, a regulator of inflammation and innate immunity. Although identified many years ago, the role of the FIIND is unknown. Here, we report that CARD8 and NLRP1 undergo autoproteolytic cleavage at a conserved SF/S motif within the FIIND. Using bioinformatics and computational modeling approaches, we detected striking structural similarity between the FIIND and the ZU5-UPA domain present in the autoproteolytic protein PIDD. This allowed us to generate a three-dimensional model and to gain insights in the molecular mechanism of the cleavage. Site-directed mutagenesis experiments revealed that the second serine of the SF/S motif is required for CARD8 and NLRP1 autoproteolysis. Furthermore, we discovered an important function for conserved glutamic acid and histidine residues, located in proximity of the cleavage site in regulating the autoprocessing efficiency. Altogether, these results identify a function for the FIIND and show that CARD8 and NLRP1 are ZU5-UPA domain containing autoproteolytic proteins, thus suggesting a novel mechanism for regulating innate immune responses. PMID- 22087308 TI - DNA damage stress and inhibition of Jak2-V617F cause its degradation and synergistically induce apoptosis through activation of GSK3beta. AB - The cytoplasmic tyrosine kinase Jak2 plays a crucial role in cytokine receptor signaling in hematopoietic cells. The activated Jak2-V617F mutant is present in most cases of BCR/ABL-negative myeloproliferative neoplasms and constitutively activates downstream signals from homodimeric cytokine receptors, such as the erythropoietin receptor (EpoR). Here we examine the effects of DNA damage stress on Jak2 or Jak2-V617F and on induction of apoptosis in hematopoietic cells. Etoposide or doxorubicin dose-dependently decreased the expression level of Jak2 in UT7 or 32D cells expressing EpoR in the absence of Epo and that of exogenously expressed Jak2-V617F in UT7 cells when cotreated with the Jak2 inhibitor JakI-1 or AG490. Studies with pharmacological inhibitors and genetic manipulations further showed that downregulation of the PI3K/Akt pathway leading to the activation of GSK3beta may be involved in downregulation of Jak2 or Jak2-V617F as well as in synergistic induction of Bax activation and apoptosis. The downregulation of Jak2 was inhibited by the proteasome inhibitor MG132 or by expression of both of loss-of-function mutants of c-Cbl and Cbl-b, E3 ubiquitin ligases which facilitated ubiquitination of Jak2-V617F when co-expressed in 293T cells. The pan-caspase inhibitor Boc-d-fmk also inhibited the Jak2 downregulation as well as appearance of a 100-kDa fragment that contained the N-terminal portion of Jak2 in response to DNA damage. Together, these data suggest that DNA damage stress with simultaneous inhibition of the kinase activity causes degradation of Jak2 or Jak2-V617F by caspase cleavage and proteasomal degradation through GSK3beta activation, which is closely involved in synergistic induction of apoptosis in hematopoietic cells. PMID- 22087309 TI - Lymphangiogenesis in regional lymph nodes is an independent prognostic marker in rectal cancer patients after neoadjuvant treatment. AB - One of the major prognostic factors in rectal cancer is lymph node metastasis. The formation of lymph node metastases is dependent on the existence of a premetastatic niche. An important factor preceding metastasis are lymph vessels which are located in the lymph node. Accordingly, the occurrence of intranodal lymphangiogenesis is thought to indicate distant metastasis and worse prognosis. To evaluate the significance of lymph node lymphangiogenesis, we studied formalin fixed, paraffin embedded adenocarcinomas and regional lymph nodes of 203 rectal cancer patients who were treated with neoadjuvant radiochemotherapy and consecutive curative surgery with cancer free surgical margins (R0). Regional lymph node lymph vessels were detected by immunohistochemistry for podoplanin (D2 40). Our results show that the presence of lymphatic vessels in regional lymph nodes significantly affects the disease-free survival in univariate and multivariate analyses. In contrast, there was no correlation between peritumoral or intratumoral lymph vessel density and prognosis. Indeed, our study demonstrates the importance of lymphangiogenesis in regional lymph nodes after neoadjuvant radiochemotherapy and consecutive surgery as an independent prognostic marker. Staining for intranodal lymphangiogenesis and methods of intravital imaging of lymphangiogenesis and lymphatic flow may be a useful strategy to predict long-term outcome in rectal cancer patients. Furthermore, addition of VEGF-blocking agents to standardized neoadjuvant treatment schemes might be indicated in advanced rectal cancer. PMID- 22087310 TI - A plant virus movement protein regulates the Gcn2p kinase in budding yeast. AB - Virus life cycle heavily depends on their ability to command the host machinery in order to translate their genomes. Animal viruses have been shown to interfere with host translation machinery by expressing viral proteins that either maintain or inhibit eIF2alpha function by phosphorylation. However, this interference mechanism has not been described for any plant virus yet. Prunnus necrotic ringspot virus (PNRSV) is a serious pathogen of cultivated stone fruit trees. The movement protein (MP) of PNRSV is necessary for the cell-to-cell movement of the virus. By using a yeast-based approach we have found that over-expression of the PNRSV MP caused a severe growth defect in yeast cells. cDNA microarrays analysis carried out to characterise at the molecular level the growth interference phenotype reported the induction of genes related to amino acid deprivation suggesting that expression of MP activates the GCN pathway in yeast cells. Accordingly, PNRSV MP triggered activation of the Gcn2p kinase, as judged by increased eIF2alpha phosphorylation. Activation of Gcn2p by MP expression required a functional Tor1p kinase, since rapamycin treatment alleviated the yeast cell growth defect and blocked eIF2alpha phosphorylation triggered by MP expression. Overall, these findings uncover a previously uncharacterised function for PNRSV MP viral protein, and point out at Tor1p and Gcn2p kinases as candidate susceptibility factors for plant viral infections. PMID- 22087311 TI - Elevated N-terminal pro-brain natriuretic peptide is associated with mortality in tobacco smokers independent of airflow obstruction. AB - BACKGROUND: Tobacco use is associated with an increased prevalence of cardiovascular disease. N-terminal pro-brain natiuretic peptide (NT-proBNP), a widely available biomarker that is associated with cardiovascular outcomes in other conditions, has not been investigated as a predictor of mortality in tobacco smokers. We hypothesized that NT-proBNP would be an independent prognostic marker in a cohort of well-characterized tobacco smokers without known cardiovascular disease. METHODS: Clinical data from 796 subjects enrolled in two prospective tobacco exposed cohorts was assessed to determine factors associated with elevated NT-proBNP and the relationship of these factors and NT-proBNP with mortality. RESULTS: Subjects were followed for a median of 562 (IQR 252-826) days. Characteristics associated with a NT-proBNP above the median (>=49 pg/mL) were increased age, female gender, and decreased body mass index. By time-to event analysis, an NT-proBNP above the median (>=49 pg/mL) was a significant predictor of mortality (log rank p = 0.02). By proportional hazard analysis controlling for age, gender, cohort, and severity of airflow obstruction, an elevated NT-proBNP level (>=49 pg/mL) remained an independent predictor of mortality (HR = 2.19, 95% CI 1.07-4.46, p = 0.031). CONCLUSIONS: Elevated NT proBNP is an independent predictor of mortality in tobacco smokers without known cardiovascular disease, conferring a 2.2 fold increased risk of death. Future studies should assess the ability of this biomarker to guide further diagnostic testing and to direct specific cardiovascular risk reduction inventions that may positively impact quality of life and survival. PMID- 22087312 TI - Unbiased and automated identification of a circulating tumour cell definition that associates with overall survival. AB - Circulating tumour cells (CTC) in patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. Classification of CTC however remains subjective, as they are morphologically heterogeneous. We acquired digital images, using the CellSearchTM system, from blood of 185 castration resistant prostate cancer (CRPC) patients and 68 healthy subjects to define CTC by computer algorithms. Patient survival data was used as the training parameter for the computer to define CTC. The computer-generated CTC definition was validated on a separate CRPC dataset comprising 100 patients. The optimal definition of the computer defined CTC (aCTC) was stricter as compared to the manual CellSearch CTC (mCTC) definition and as a consequence aCTC were less frequent. The computer-generated CTC definition resulted in hazard ratios (HRs) of 2.8 for baseline and 3.9 for follow-up samples, which is comparable to the mCTC definition (baseline HR 2.9, follow-up HR 4.5). Validation resulted in HRs at baseline/follow-up of 3.9/5.4 for computer and 4.8/5.8 for manual definitions. In conclusion, we have defined and validated CTC by clinical outcome using a perfectly reproducing automated algorithm. PMID- 22087313 TI - Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. AB - In type 2 Diabetes (T2D) free fatty acids (FFAs) in plasma are increased and hepatic insulin resistance is "selective", in the sense that the insulin-mediated decrease of glucose production is blunted while insulin's effect on stimulating lipogenesis is maintained. We investigated the molecular mechanisms underlying this pathogenic paradox. Primary rat hepatocytes were exposed to palmitate for twenty hours. To establish the physiological relevance of the in vitro findings, we also studied insulin-resistant Zucker Diabetic Fatty (ZDF) rats. While insulin receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3alpha (Gsk3alpha and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. Accordingly, dose response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. In contrast, similar to findings in human T2D, the ability of insulin to induce triglyceride (TG) accumulation and transcription of the enzymes that catalyze de novo lipogenesis and TG assembly was unaffected. Insulin-induction of these genes could, however, be blocked by inhibition of the atypical PKCs (aPKCs). The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3alpha. Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. PMID- 22087314 TI - Novel common integration sites targeted by mouse mammary tumor virus insertion in mammary tumors have oncogenic activity. AB - Non-acute transforming retroviruses like mouse mammary tumor virus (MMTV) cause cancer, at least in part, through integration near cellular genes involved in growth control, thereby de-regulating their expression. It is well-established that MMTV commonly integrates near and activates expression of members of the Wnt and Fgf pathways in mammary tumors. However, there are a significant number of tumors for which the proviral integration sites have not been identified. Here, we used high through-put screening to identify common integration sites (CISs) in MMTV-induced tumors from C3H/HeN and BALB/c mice. As expected, members of both the Wnt and Fgf families were identified in this screen. In addition, a number of novel CISs were found, including Tcf7l2, Antxr1/Tem8, and Arhgap18. We show here that expression of these three putative oncogenes in normal murine mammary gland cells altered their growth kinetics and caused their morphological transformation when grown in three dimensional cultures. Additionally, expression of Tcf7l2 and Antxr1/Tem8 sensitized cells to exogenous WNT ligand. As Tcf7l2, Antxr1/Tem8, and Arhgap18 have been associated with human breast and other cancers, these data demonstrate that MMTV-induced insertional mutation remains an important means for identifying genes involved in breast cancer. PMID- 22087315 TI - AF17 facilitates Dot1a nuclear export and upregulates ENaC-mediated Na+ transport in renal collecting duct cells. AB - Our previous work in 293T cells and AF17(-/-) mice suggests that AF17 upregulates expression and activity of the epithelial Na(+) channel (ENaC), possibly by relieving Dot1a-AF9-mediated repression. However, whether and how AF17 directly regulates Dot1a cellular distribution and ENaC function in renal collecting duct cells remain unaddressed. Here, we report our findings in mouse cortical collecting duct M-1 cells that overexpression of AF17 led to preferential distribution of Dot1a in the cytoplasm. This effect could be blocked by nuclear export inhibitor leptomycin B. siRNA-mediated depletion of AF17 caused nuclear accumulation of Dot1a. AF17 overexpression elicited multiple effects that are reminiscent of aldosterone action. These effects include 1) increased mRNA and protein expression of the three ENaC subunits (alpha, beta and gamma) and serum- and glucocorticoid inducible kinase 1, as revealed by real-time RT-qPCR and immunoblotting analyses; 2) impaired Dot1a-AF9 interaction and H3 K79 methylation at the alphaENaC promoter without affecting AF9 binding to the promoter, as evidenced by chromatin immunoprecipitation; and 3) elevated ENaC-mediated Na(+) transport, as analyzed by measurement of benzamil-sensitive intracellular [Na(+)] and equivalent short circuit current using single-cell fluorescence imaging and an epithelial Volt-ohmmeter, respectively. Knockdown of AF17 elicited opposite effects. However, combination of AF17 overexpression or depletion with aldosterone treatment did not cause an additive effect on mRNA expression of the ENaC subunits. Taken together, we conclude that AF17 promotes Dot1a nuclear export and upregulates basal, but not aldosterone-stimulated ENaC expression, leading to an increase in ENaC-mediated Na(+) transport in renal collecting duct cells. PMID- 22087317 TI - Predicting the timing of cherry blossoms in Washington, DC and Mid-Atlantic States in response to climate change. AB - Cherry blossoms, an icon of spring, are celebrated in many cultures of the temperate region. For its sensitivity to winter and early spring temperatures, the timing of cherry blossoms is an ideal indicator of the impacts of climate change on tree phenology. Here, we applied a process-based phenology model for temperate deciduous trees to predict peak bloom dates (PBD) of flowering cherry trees (Prunus*yedoensis 'Yoshino' and Prunus serrulata 'Kwanzan') in the Tidal Basin, Washington, DC and the surrounding Mid-Atlantic States in response to climate change. We parameterized the model with observed PBD data from 1991 to 2010. The calibrated model was tested against independent datasets of the past PBD data from 1951 to 1970 in the Tidal Basin and more recent PBD data from other locations (e.g., Seattle, WA). The model performance against these independent data was satisfactory (Yoshino: r(2) = 0.57, RMSE = 6.6 days, bias = 0.9 days and Kwanzan: r(2) = 0.76, RMSE = 5.5 days, bias = -2.0 days). We then applied the model to forecast future PBD for the region using downscaled climate projections based on IPCC's A1B and A2 emissions scenarios. Our results indicate that PBD at the Tidal Basin are likely to be accelerated by an average of five days by 2050 s and 10 days by 2080 s for these cultivars under a mid-range (A1B) emissions scenario projected by ECHAM5 general circulation model. The acceleration is likely to be much greater (13 days for 2050 s and 29 days for 2080s) under a higher (A2) emissions scenario projected by CGCM2 general circulation model. Our results demonstrate the potential impacts of climate change on the timing of cherry blossoms and illustrate the utility of a simple process-based phenology model for developing adaptation strategies to climate change in horticulture, conservation planning, restoration and other related disciplines. PMID- 22087316 TI - Ethanol and reactive species increase basal sequence heterogeneity of hepatitis C virus and produce variants with reduced susceptibility to antivirals. AB - Hepatitis C virus (HCV) exhibits a high level of genetic variability, and variants with reduced susceptibility to antivirals can occur even before treatment begins. In addition, alcohol decreases efficacy of antiviral therapy and increases sequence heterogeneity of HCV RNA but how ethanol affects HCV sequence is unknown. Ethanol metabolism and HCV infection increase the level of reactive species that can alter cell metabolism, modify signaling, and potentially act as mutagen to the viral RNA. Therefore, we investigated whether ethanol and reactive species affected the basal sequence variability of HCV RNA in hepatocytes. Human hepatoma cells supporting a continuous replication of genotype 1b HCV RNA (Con1, AJ242652) were exposed to ethanol, acetaldehyde, hydrogen peroxide, or L-buthionine-S,R-sulfoximine (BSO) that decreases intracellular glutathione as seen in patients. Then, NS5A region was sequenced and compared with genotype 1b HCV sequences in the database. Ethanol and BSO elevated nucleotide and amino acid substitution rates of HCV RNA by 4-18 folds within 48 hrs which were accompanied by oxidative RNA damage. Iron chelator and glutathione ester decreased both RNA damage and mutation rates. Furthermore, infectious HCV and HCV core gene were sufficient to induce oxidative RNA damage even in the absence of ethanol or BSO. Interestingly, the dn/ds ratio and percentage of sites undergoing positive selection increased with ethanol and BSO, resulting in an increased detection of NS5A variants with reduced susceptibility to interferon alpha, cyclosporine, and ribavirin and others implicated in immune tolerance and modulation of viral replication. Therefore, alcohol is likely to synergize with virus-induced oxidative/nitrosative stress to modulate the basal mutation rate of HCV. Positive selection induced by alcohol and reactive species may contribute to antiviral resistance. PMID- 22087318 TI - Grape proanthocyanidins induce apoptosis by loss of mitochondrial membrane potential of human non-small cell lung cancer cells in vitro and in vivo. AB - Lung cancer remains the leading cause of cancer-related deaths worldwide, and non small cell lung cancer (NSCLC) represents approximately 80% of total lung cancer cases. The use of non-toxic dietary phytochemicals can be considered as a chemotherapeutic strategy for the management of the NSCLC. Here, we report that grape seed proanthocyanidins (GSPs) induce apoptosis of NSCLC cells, A549 and H1299, in vitro which is mediated through increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspases 9, 3 and poly (ADP-ribose) polymerase (PARP). Pre-treatment of A549 and H1299 cells with the caspase-3 inhibitor (z-DEVD-fmk) significantly blocked the GSPs-induced apoptosis of these cells confirmed that GSPs-induced apoptosis is mediated through activation of caspases-3. Treatments of A549 and H1299 cells with GSPs resulted in an increase in G1 arrest. G0/G1 phase of the cell cycle is known to be controlled by cyclin dependent kinases (Cdk), cyclin-dependent kinase inhibitors (Cdki) and cyclins. Our western blot analyses showed that GSPs-induced G1 cell cycle arrest was mediated through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27), and a simultaneous decrease in the levels of Cdk2, Cdk4, Cdk6 and cyclins. Further, administration of 50, 100 or 200 mg GSPs/kg body weight of mice by oral gavage (5 d/week) markedly inhibited the growth of s.c. A549 and H1299 lung tumor xenografts in athymic nude mice, which was associated with the induction of apoptotic cell death, increased expression of Bax, reduced expression of anti-apoptotic proteins and activation of caspase-3 in tumor xenograft cells. Based on the data obtained in animal study, human equivalent dose of GSPs was calculated, which seems affordable and attainable. Together, these results suggest that GSPs may represent a potential therapeutic agent for the non-small cell lung cancer. PMID- 22087319 TI - External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement. AB - BACKGROUND: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well known prognostic factors. PATIENTS AND METHODS: The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction. RESULTS: Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old. CONCLUSION: Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index. PMID- 22087320 TI - 8-Modified-2'-deoxyadenosine analogues induce delayed polymerization arrest during HIV-1 reverse transcription. AB - The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV 1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix alphaH in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2'-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2'-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication. PMID- 22087321 TI - Enhanced understanding of infectious diseases by fusing multiple datasets: a case study on malaria in the Western Brazilian Amazon region. AB - BACKGROUND: A common challenge to the study of several infectious diseases consists in combining limited cross-sectional survey data, collected with a more sensitive detection method, with a more extensive (but biased) syndromic sentinel surveillance data, collected with a less sensitive method. Our article describes a novel modeling framework that overcomes this challenge, resulting in enhanced understanding of malaria in the Western Brazilian Amazon. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 486 individuals was monitored using four cross-sectional surveys, where all participants were sampled regardless of symptoms (aggressive active case detection), resulting in 1,383 microscopy and 1,400 polymerase chain reaction tests. Data on the same individuals were also obtained from the local surveillance facility (i.e., passive and active case detection), totaling 1,694 microscopy tests. Our model accommodates these multiple pathogen and case detection methods. This model is shown to outperform logistic regression in terms of interpretability of its parameters, ability to recover the true parameter values, and predictive performance. We reveal that the main infection determinant was the extent of forest, particularly during the rainy season and in close proximity to water bodies, and participation on forest activities. We find that time residing in Acrelandia (as a proxy for past malaria exposure) decreases infection risk but surprisingly increases the likelihood of reporting symptoms once infected, possibly because non-naive settlers are only susceptible to more virulent Plasmodium strains. We suggest that the search for asymptomatic carriers should focus on those at greater risk of being infected but lower risk of reporting symptoms once infected. CONCLUSIONS/SIGNIFICANCE: The modeling framework presented here combines cross-sectional survey data and syndromic sentinel surveillance data to shed light on several aspects of malaria that are critical for public health policy. This framework can be adapted to enhance inference on infectious diseases whenever asymptomatic carriers are important and multiple datasets are available. PMID- 22087322 TI - Regulation of interleukin-10 receptor ubiquitination and stability by beta-TrCP containing ubiquitin E3 ligase. AB - Interleukin-10 (IL-10) initiates potent anti-inflammatory effects via activating its cell surface receptor, composed of IL-10R1 and IL-10R2 subunits. The level of IL-10R1 is a major determinant of the cells' responsiveness to IL-10. Here, via a series of biochemical analyses using 293T cells reconstituted with IL-10R1, we identify the latter as a novel substrate of betaTrCP-containing ubiquitin E3 ligase. Within the intracellular tail of IL-10R1, a canonical ((318)DpSGFGpS) and a slightly deviated ((369)DpSGICLQEP) betaTrCP recognition motif can additively recruit betaTrCP in a phosphorylation-dependent manner. betaTrCP recruitment leads to ubiquitination, endocytosis and degradation of IL-10R1, subsequently reducing the cellular responsiveness to IL-10. Our study uncovers a novel negative regulatory mechanism that may potentially affect IL-10 function in target cells under physiological or pathological conditions. PMID- 22087323 TI - Comparison of two devices and two breathing patterns for exhaled breath condensate sampling. AB - INTRODUCTION: Analysis of exhaled breath condensate (EBC) is a noninvasive method to access the epithelial lining fluid of the lungs. Due to standardization problems the method has not entered clinical practice. The aim of the study was to assess the comparability for two commercially available devices in healthy controls. In addition, we assessed different breathing patterns in healthy controls with protein markers to analyze the source of the EBC. METHODS: EBC was collected from ten subjects using the RTube and ECoScreen Turbo in a randomized crossover design, twice with every device--once in tidal breathing and once in hyperventilation. EBC conductivity, pH, surfactant protein A, Clara cell secretory protein and total protein were assessed. Bland-Altman plots were constructed to display the influence of different devices or breathing patterns and the intra-class correlation coefficient (ICC) was calculated. The volatile organic compound profile was measured using the electronic nose Cyranose 320. For the analysis of these data, the linear discriminant analysis, the Mahalanobis distances and the cross-validation values (CVV) were calculated. RESULTS: Neither the device nor the breathing pattern significantly altered EBC pH or conductivity. ICCs ranged from 0.61 to 0.92 demonstrating moderate to very good agreement. Protein measurements were greatly influenced by breathing pattern, the device used, and the way in which the results were reported. The electronic nose could distinguish between different breathing patterns and devices, resulting in Mahalanobis distances greater than 2 and CVVs ranging from 64% to 87%. CONCLUSION: EBC pH and (to a lesser extent) EBC conductivity are stable parameters that are not influenced by either the device or the breathing patterns. Protein measurements remain uncertain due to problems of standardization. We conclude that the influence of the breathing maneuver translates into the necessity to keep the volume of ventilated air constant in further studies. PMID- 22087324 TI - The role of purinergic signaling on deformation induced injury and repair responses of alveolar epithelial cells. AB - Cell wounding is an important driver of the innate immune response of ventilator injured lungs. We had previously shown that the majority of wounded alveolus resident cells repair and survive deformation induced insults. This is important insofar as wounded and repaired cells may contribute to injurious deformation responses commonly referred to as biotrauma. The central hypothesis of this communication states that extracellular adenosine-5' triphosphate (ATP) promotes the repair of wounded alveolus resident cells by a P2Y2-Receptor dependent mechanism. Using primary type 1 alveolar epithelial rat cell models subjected to micropuncture injury and/or deforming stress we show that 1) stretch causes a dose dependent increase in cell injury and ATP media concentrations; 2) enzymatic depletion of extracellular ATP reduces the probability of stretch induced wound repair; 3) enriching extracellular ATP concentrations facilitates wound repair; 4) purinergic effects on cell repair are mediated by ATP and not by one of its metabolites; and 5) ATP mediated cell salvage depends at least in part on P2Y2-R activation. While rescuing cells from wounding induced death may seem appealing, it is possible that survivors of membrane wounding become governors of a sustained pro-inflammatory state and thereby perpetuate and worsen organ function in the early stages of lung injury syndromes. Means to uncouple P2Y2-R mediated cytoprotection from P2Y2-R mediated inflammation and to test the preclinical efficacy of such an undertaking deserve to be explored. PMID- 22087325 TI - Combined phytochemistry and chemotaxis assays for identification and mechanistic analysis of anti-inflammatory phytochemicals in Fallopia japonica. AB - Plants provide a rich source of lead compounds for a variety of diseases. A novel approach combining phytochemistry and chemotaxis assays was developed and used to identify and study the mechanisms of action of the active compounds in F. japonica, a medicinal herb traditionally used to treat inflammation. Based on a bioactivity-guided purification strategy, two anthranoids, emodin and physcion, were identified from F. japonica. Spectroscopic techniques were used to characterize its crude extract, fractions and phytochemicals. The crude extract, chloroform fraction, and anthranoids of F. japonica significantly inhibited CXCR4 mediated chemotaxis. Mechanistic studies showed that emodin and physcion inhibited chemotaxis via inactivating the MEK/ERK pathway. Moreover, the crude extract and emodin could prevent or treat type 1 diabetes in non-obese diabetic (NOD) mice. This study illustrates the applicability of a combinational approach for the study of anti-inflammatory medicine and shows the potential of F. japonica and its anthranoids for anti-inflammatory therapy. PMID- 22087327 TI - Memory in the neonate brain. AB - BACKGROUND: The capacity to memorize speech sounds is crucial for language acquisition. Newborn human infants can discriminate phonetic contrasts and extract rhythm, prosodic information, and simple regularities from speech. Yet, there is scarce evidence that infants can recognize common words from the surrounding language before four months of age. METHODOLOGY/PRINCIPAL FINDINGS: We studied one hundred and twelve 1-5 day-old infants, using functional near infrared spectroscopy (fNIRS). We found that newborns tested with a novel bisyllabic word show greater hemodynamic brain response than newborns tested with a familiar bisyllabic word. We showed that newborns recognize the familiar word after two minutes of silence or after hearing music, but not after hearing a different word. CONCLUSIONS/SIGNIFICANCE: The data show that retroactive interference is an important cause of forgetting in the early stages of language acquisition. Moreover, because neonates forget words in the presence of some--but not all--sounds, the results indicate that the interference phenomenon that causes forgetting is selective. PMID- 22087326 TI - Dissociation of bone resorption and bone formation in adult mice with a non functional V-ATPase in osteoclasts leads to increased bone strength. AB - Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption.To shed light on the effect of uncoupling in adult mice with respect to bone strength, we transplanted irradiated three-month old normal mice with hematopoietic stem cells from control or oc/oc mice, which have defective acid secretion, and followed them for 12 to 28 weeks.Engraftment levels were assessed by flow cytometry of peripheral blood. Serum samples were collected every six weeks for measurement of bone turnover markers. At termination bones were collected for uCT and mechanical testing. An engraftment level of 98% was obtained. From week 6 until termination bone resorption was significantly reduced, while the osteoclast number was increased when comparing oc/oc to controls. Bone formation was elevated at week 6, normalized at week 12, and reduced onwards. uCT and mechanical analyses of femurs and vertebrae showed increased bone volume and bone strength of cortical and trabecular bone.In conclusion, these data show that attenuation of acid secretion in adult mice leads to uncoupling and improves bone strength. PMID- 22087328 TI - Functional transforming growth factor-beta receptor type II expression by CD4+ T cells in Peyer's patches is essential for oral tolerance induction. AB - Our previous studies have shown that Peyer's patches (PPs) play a key role in the induction of oral tolerance. Therefore, we hypothesized that PPs are an important site for Transforming Growth Factor (TGF)-beta signaling and sought to prove that this tissue is of importance in oral tolerance induction. We found that expression of TGF-beta type II receptor (TGFbetaRII) by CD4(+) T cells increases and persists in the PPs of normal C57BL/6 mice after either high- or low-dose feeding of OVA when compared to mesenteric lymph nodes (MLNs) and spleen. Approximately one-third of these TGFbetaRII(+) CD4(+) T cells express the transcription factor Foxp3. Interestingly, the number of TGFbetaRII(+) CD4(+) T cells in PPs decreased when OVA-fed mice were orally challenged with OVA plus native cholera toxin (CT). In contrast, numbers of TGFbetaRII(+) CD4(+) T cells were increased in the intestinal lamina propria (iLP) of these challenged mice. Further, these PP CD4(+) TGFbetaRII(+) T cells upregulated Foxp3 within 2 hours after OVA plus CT challenge. Mice fed PBS and challenged with OVA plus CT did not reveal any changes in TGFbetaRII expression by CD4(+) T cells. In order to test the functional property of TGFbetaRII in the induction of oral tolerance, CD4dnTGFbetaRII transgenic mice, in which TGFbetaRII signaling is abrogated from all CD4(+) T cells, were employed. Importantly, these mice could not develop oral tolerance to OVA. Our studies show a critical, dose-independent, role for TGFbetaRII expression and function by CD4(+) T cells in the gut-associated lymphoid tissues, further underlining the vital role of PPs in oral tolerance. PMID- 22087329 TI - Borrelia burgdorferi enolase is a surface-exposed plasminogen binding protein. AB - Borrelia burgdorferi is the causative agent of Lyme disease, the most commonly reported arthropod-borne disease in the United States. B. burgdorferi is a highly invasive bacterium, yet lacks extracellular protease activity. In order to aid in its dissemination, B. burgdorferi binds plasminogen, a component of the hosts' fibrinolytic system. Plasminogen bound to the surface of B. burgdorferi can then be activated to the protease plasmin, facilitating the bacterium's penetration of endothelial cell layers and degradation of extracellular matrix components. Enolases are highly conserved proteins with no sorting sequences or lipoprotein anchor sites, yet many bacteria have enolases bound to their outer surfaces. B. burgdorferi enolase is both a cytoplasmic and membrane associated protein. Enolases from other pathogenic bacteria are known to bind plasminogen. We confirmed the surface localization of B. burgdorferi enolase by in situ protease degradation assay and immunoelectron microscopy. We then demonstrated that B. burgdorferi enolase binds plasminogen in a dose-dependent manner. Lysine residues were critical for binding of plasminogen to enolase, as the lysine analog epsilonaminocaproic acid significantly inhibited binding. Ionic interactions did not play a significant role in plasminogen binding by enolase, as excess NaCl had no effects on the interaction. Plasminogen bound to recombinant enolase could be converted to active plasmin. We conclude that B. burgdorferi enolase is a moonlighting cytoplasmic protein which also associates with the bacterial outer surface and facilitates binding to host plasminogen. PMID- 22087330 TI - A three-hybrid system to probe in vivo protein-protein interactions: application to the essential proteins of the RD1 complex of M. tuberculosis. AB - BACKGROUND: Protein-protein interactions play a crucial role in enabling a pathogen to survive within a host. In many cases the interactions involve a complex of proteins rather than just two given proteins. This is especially true for pathogens like M. tuberculosis that are able to successfully survive the inhospitable environment of the macrophage. Studying such interactions in detail may help in developing small molecules that either disrupt or augment the interactions. Here, we describe the development of an E. coli based bacterial three-hybrid system that can be used effectively to study ternary protein complexes. METHODOLOGY/PRINCIPAL FINDINGS: The protein-protein interactions involved in M. tuberculosis pathogenesis have been used as a model for the validation of the three-hybrid system. Using the M. tuberculosis RD1 encoded proteins CFP10, ESAT6 and Rv3871 for our proof-of-concept studies, we show that the interaction between the proteins CFP10 and Rv3871 is strengthened and stabilized in the presence of ESAT6, the known heterodimeric partner of CFP10. Isolating peptide candidates that can disrupt crucial protein-protein interactions is another application that the system offers. We demonstrate this by using CFP10 protein as a disruptor of a previously established interaction between ESAT6 and a small peptide HCL1; at the same time we also show that CFP10 is not able to disrupt the strong interaction between ESAT6 and another peptide SL3. CONCLUSIONS/SIGNIFICANCE: The validation of the three-hybrid system paves the way for finding new peptides that are stronger binders of ESAT6 compared even to its natural partner CFP10. Additionally, we believe that the system offers an opportunity to study tri-protein complexes and also perform a screening of protein/peptide binders to known interacting proteins so as to elucidate novel tri-protein complexes. PMID- 22087331 TI - Prediction of transposable element derived enhancers using chromatin modification profiles. AB - Experimentally characterized enhancer regions have previously been shown to display specific patterns of enrichment for several different histone modifications. We modelled these enhancer chromatin profiles in the human genome and used them to guide the search for novel enhancers derived from transposable element (TE) sequences. To do this, a computational approach was taken to analyze the genome-wide histone modification landscape characterized by the ENCODE project in two human hematopoietic cell types, GM12878 and K562. We predicted the locations of 2,107 and 1,448 TE-derived enhancers in the GM12878 and K562 cell lines respectively. A vast majority of these putative enhancers are unique to each cell line; only 3.5% of the TE-derived enhancers are shared between the two. We evaluated the functional effect of TE-derived enhancers by associating them with the cell-type specific expression of nearby genes, and found that the number of TE-derived enhancers is strongly positively correlated with the expression of nearby genes in each cell line. Furthermore, genes that are differentially expressed between the two cell lines also possess a divergent number of TE derived enhancers in their vicinity. As such, genes that are up-regulated in the GM12878 cell line and down-regulated in K562 have significantly more TE-derived enhancers in their vicinity in the GM12878 cell line and vice versa. These data indicate that human TE-derived sequences are likely to be involved in regulating cell-type specific gene expression on a broad scale and suggest that the enhancer activity of TE-derived sequences is mediated by epigenetic regulatory mechanisms. PMID- 22087332 TI - A two-compartment model of VEGF distribution in the mouse. AB - Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis--the growth of new microvessels from existing microvasculature. Angiogenesis is a complex process involving numerous molecular species, and to better understand it, a systems biology approach is necessary. In vivo preclinical experiments in the area of angiogenesis are typically performed in mouse models; this includes drug development targeting VEGF. Thus, to quantitatively interpret such experimental results, a computational model of VEGF distribution in the mouse can be beneficial. In this paper, we present an in silico model of VEGF distribution in mice, determine model parameters from existing experimental data, conduct sensitivity analysis, and test the validity of the model. The multiscale model is comprised of two compartments: blood and tissue. The model accounts for interactions between two major VEGF isoforms (VEGF(120) and VEGF(164)) and their endothelial cell receptors VEGFR-1, VEGFR-2, and co-receptor neuropilin-1. Neuropilin-1 is also expressed on the surface of parenchymal cells. The model includes transcapillary macromolecular permeability, lymphatic transport, and macromolecular plasma clearance. Simulations predict that the concentration of unbound VEGF in the tissue is approximately 50-fold greater than in the blood. These concentrations are highly dependent on the VEGF secretion rate. Parameter estimation was performed to fit the simulation results to available experimental data, and permitted the estimation of VEGF secretion rate in healthy tissue, which is difficult to measure experimentally. The model can provide quantitative interpretation of preclinical animal data and may be used in conjunction with experimental studies in the development of pro- and anti-angiogenic agents. The model approximates the normal tissue as skeletal muscle and includes endothelial cells to represent the vasculature. As the VEGF system becomes better characterized in other tissues and cell types, the model can be expanded to include additional compartments and vascular elements. PMID- 22087333 TI - Intentional modulation of the late positive potential in response to smoking cues by cognitive strategies in smokers. AB - Attentional bias is considered an important concept in addiction since it has been found to correlate with subjective craving and is strongly associated with relapse after periods of abstinence. Hence, investigating in ways to regulate attention for drug cues would be of major clinical relevance. The present study examined deliberate, cognitive modulation of motivated attention for smoking cues in smokers. The effects of three different reappraisal strategies on an electrophysiological measure of attentive processing were investigated. Early and late LPP components in response to passively viewed neutral and smoking pictures were compared with LPPs in response to smoking pictures that were reappraised with three different reappraisal strategies. Results show that when smokers actively imagine how pleasant it would be to smoke (pleasant condition), their early LPP in response to smoking cues increases, but when smokers actively focus on an alternative stimulus (distraction condition) or think of a rational, uninvolved interpretation of the situation (rational condition), smoking-related late LPP amplitude decreases to the processing level of neutral stimuli. Present results are the first to indicate that smoking cue-elicited LPP amplitudes can be modulated by cognitive strategies, suggesting that attentive processing of smoking cues can be intentionally regulated by smokers with various levels of dependence. Although cognitive strategies can lead to enhanced processing of smoking cues, it is not completely clear whether cognitive strategies are also successful in reducing smoking-related motivated attention. Although findings do point in this direction, present study is best considered preliminary and a starting point for other research on this topic. A focus on the distraction strategy is proposed, as there are indications that this strategy is more successful than the rational strategy in decreasing LPP amplitude. PMID- 22087334 TI - Multigenic families in Ichnovirus: a tissue and host specificity study through expression analysis of vankyrins from Hyposoter didymator Ichnovirus. AB - The viral ankyrin (vankyrin) gene family is represented in all polydnavirus (PDVs) genomes and encodes proteins homologous to I-kappaBs, inhibitors of NF kappaB transcription factors. The structural similarities led to the hypothesis that vankyrins mimic eukaryotic factors to subvert important physiological pathways in the infected host. Here, we identified nine vankyrin genes in the genome of the Hyposoter didymator Ichnovirus (HdIV). Time-course gene expression experiments indicate that all members are expressed throughout parasitism of Spodoptera frugiperda, as assessed using RNA extracted from whole larvae. To study tissue and/or species specificity transcriptions, the expression of HdIV vankyrin genes were compared between HdIV-injected larvae of S. frugiperda and S. littoralis. The transcriptional profiles were similar in the two species, including the largely predominant expression of Hd27-vank1 in all tissues examined. However, in various insect cell lines, the expression patterns of HdIV vankyrins differed according to species. No clear relationship between vankyrin expression patterns and abundance of vankyrin-bearing genomic segments were found in the lepidopteran cell lines. Moreover, in these cells, the amount of vankyrin bearing genomic segments differed substantially between cytosol and nuclei of infected cells, implying the existence of an unexpected step regulating the copy number of HdIV segments in cell nuclei. Our in vitro results reveal a host specific transcriptional profile of vankyrins that may be related to the success of parasitism in different hosts. In Spodoptera hosts, the predominant expression of Hd27-vank1 suggests that this protein might have pleiotropic functions during parasitism of these insect species. PMID- 22087335 TI - Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice. AB - Dental pulp stem cells (DPSCs) are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s) have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs) gave rise to osteoblast like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues. PMID- 22087336 TI - SdPI, the first functionally characterized Kunitz-type trypsin inhibitor from scorpion venom. AB - BACKGROUND: Kunitz-type venom peptides have been isolated from a wide variety of venomous animals. They usually have protease inhibitory activity or potassium channel blocking activity, which by virtue of the effects on predator animals are essential for the survival of venomous animals. However, no Kunitz-type peptides from scorpion venom have been functionally characterized. PRINCIPAL FINDINGS: A new Kunitz-type venom peptide gene precursor, SdPI, was cloned and characterized from a venom gland cDNA library of the scorpion Lychas mucronatus. It codes for a signal peptide of 21 residues and a mature peptide of 59 residues. The mature SdPI peptide possesses a unique cysteine framework reticulated by three disulfide bridges, different from all reported Kunitz-type proteins. The recombinant SdPI peptide was functionally expressed. It showed trypsin inhibitory activity with high potency (K(i) = 1.6*10(-7) M) and thermostability. CONCLUSIONS: The results illustrated that SdPI is a potent and stable serine protease inhibitor. Further mutagenesis and molecular dynamics simulation revealed that SdPI possesses a serine protease inhibitory active site similar to other Kunitz-type venom peptides. To our knowledge, SdPI is the first functionally characterized Kunitz type trypsin inhibitor derived from scorpion venom, and it represents a new class of Kunitz-type venom peptides. PMID- 22087337 TI - Innate host response in primary human hepatocytes with hepatitis C virus infection. AB - BACKGROUND AND AIM: The interaction between hepatitis C virus (HCV) and innate antiviral defense systems in primary human hepatocytes is not well understood. The objective of this study is to examine how primary human hepatocytes response to HCV infection. METHODS: An infectious HCV isolate JFH1 was used to infect isolated primary human hepatocytes. HCV RNA or NS5A protein in the cells was detected by real-time PCR or immunofluorescence staining respectively. Apoptosis was examined with flow cytometry. Mechanisms of HCV-induced IFN-beta expression and apoptosis were determined. RESULTS: Primary human hepatocytes were susceptible to JFH1 virus and released infectious virus. IFN-alpha inhibited viral RNA replication in the cells. IFN-beta and interferon-stimulated genes were induced in the cells during acute infection. HCV infection induced apoptosis of primary human hepatocytes through the TRAIL-mediated pathway. Silencing RIG-I expression in primary human hepatocytes inhibited IFN-beta and TRAIL expression and blocked apoptosis of the cells, which facilitated viral RNA replication in the cells. Moreover, HCV NS34A protein inhibited viral induced IFN-beta expression in primary human hepatocytes. CONCLUSION: Innate host response is intact in HCV-infected primary human hepatocytes. RIG-I plays a key role in the induction of IFN and TRAIL by viruses and apoptosis of primary human hepatocytes via activation of the TRAIL-mediated pathway. HCV NS34A protein appears to be capable of disrupting the innate antiviral host responses in primary human hepatocytes. Our study provides a novel mechanism by which primary human hepatocytes respond to natural HCV infection. PMID- 22087338 TI - Stable small animal ventilation for dynamic lung imaging to support computational fluid dynamics models. AB - Pulmonary computational fluid dynamics models require that three-dimensional images be acquired over multiple points in the dynamic breathing cycle without breath holds or changes in ventilatory mechanics. With small animals, these requirements can result in long imaging times (~90 minutes), over which lung mechanics, such as compliance, may gradually change if not carefully monitored and controlled. These changes, caused by derecruitment of parenchymal tissue, are manifested as an upward drift in peak inspiratory pressure (PIP) or by changes in the pressure waveform and/or lung volume over the course of the experiment. We demonstrate highly repeatable mechanical ventilation in anesthetized rats over a long duration for dynamic lung x-ray computed tomography (CT) imaging. We describe significant updates to a basic commercial ventilator that was acquired for these experiments. Key to achieving consistent results was the implementation of periodic deep breaths, or sighs, of extended duration to maintain lung recruitment. In addition, continuous monitoring of breath-to-breath pressure and volume waveforms and long-term trends in PIP and flow provide diagnostics of changes in breathing mechanics. PMID- 22087339 TI - Distribution of metals in the termite Tumulitermes tumuli (Froggatt): two types of Malpighian tubule concretion host Zn and Ca mutually exclusively. AB - The aim of this study was to determine specific distribution of metals in the termite Tumulitermes tumuli (Froggatt) and identify specific organs within the termite that host elevated metals and therefore play an important role in the regulation and transfer of these back into the environment. Like other insects, termites bio-accumulate essential metals to reinforce cuticular structures and utilize storage detoxification for other metals including Ca, P, Mg and K. Previously, Mn and Zn have been found concentrated in mandible tips and are associated with increased hardness whereas Ca, P, Mg and K are accumulated in Malpighian tubules. Using high resolution Particle Induced X-Ray Emission (PIXE) mapping of whole termites and Scanning Electron Microscope (SEM) Energy Dispersive X-ray (EDX) spot analysis, localised accumulations of metals in the termite T. tumuli were identified. Tumulitermes tumuli was found to have proportionally high Mn concentrations in mandible tips. Malpighian tubules had significant enrichment of Zn (1.6%), Mg (4.9%), P (6.8%), Ca (2.7%) and K (2.4%). Synchrotron scanning X-ray Fluorescence Microprobe (XFM) mapping demonstrated two different concretion types defined by the mutually exclusive presence of Ca and Zn. In-situ SEM EDX realisation of these concretions is problematic due to the excitation volume caused by operating conditions required to detect minor amounts of Zn in the presence of significant amounts of Na. For this reason, previous researchers have not demonstrated this surprising finding. PMID- 22087340 TI - Molecular typing of Treponema pallidum: a systematic review and meta-analysis. AB - BACKGROUND: Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance. METHODOLOGY/PRINCIPAL FINDINGS: Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, chi(2) = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, chi(2) = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited. CONCLUSIONS/SIGNIFICANCE: Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis. PMID- 22087341 TI - Life quality impairment caused by hookworm-related cutaneous larva migrans in resource-poor communities in Manaus, Brazil. AB - BACKGROUND: Hookworm-related cutaneous larva migrans (CLM) is a common but neglected tropical skin disease caused by the migration of animal hookworm larvae in the epidermis. The disease causes intense pruritus and is associated with important morbidity. The extent to which CLM impairs skin disease-associated life quality has never been studied. METHODS: A modified version of the Dermatology Life Quality Index (mDLQI) was used to determine skin disease-associated life quality in 91 adult and child patients with CLM, living in resource-poor communities in Manaus, Brazil. Symptoms and signs were documented and skin disease-associated life quality was semi-quantitatively assessed using mDLQI scores. The assessment was repeated two and four weeks after treatment with ivermectin. RESULTS: Ninety-one point five percent of the study participants showed a considerable reduction of skin disease-associated life quality at the time of diagnosis. The degree of impairment correlated with the intensity of infection (rho = 0.76, p<0.001), the number of body areas affected (rho = 0.30; p = 0.004), and the presence of lesions on visible areas of the skin (p = 0.002). Intense pruritus, sleep disturbance (due to itching) and the feeling of shame were the most frequent skin disease-associated life quality restrictions (reported by 93.4%, 73.6%, and 64.8% of the patients, respectively). No differences were observed in skin disease-associated life quality restriction between boys and girls or men and women. Two weeks after treatment with ivermectin, skin disease-associated life quality improved significantly. After four weeks, 73.3% of the patients considered their disease-associated life quality to have returned to normal. CONCLUSIONS: CLM significantly impaired the skin disease-associated life quality in child and adult patients living in urban slums in North Brazil. After treatment with ivermectin, life quality normalised rapidly. PMID- 22087342 TI - Comparison of two multilocus sequence based genotyping schemes for Leptospira species. AB - BACKGROUND: Several sequence based genotyping schemes have been developed for Leptospira spp. The objective of this study was to genotype a collection of clinical and reference isolates using the two most commonly used schemes and compare and contrast the results. METHODS AND FINDINGS: A total of 48 isolates consisting of L. interrogans (n = 40) and L. kirschneri (n = 8) were typed by the 7 locus MLST scheme described by Thaipadungpanit et al., and the 6 locus genotyping scheme described by Ahmed et al., (termed 7L and 6L, respectively). Two L. interrogans isolates were not typed using 6L because of a deletion of three nucleotides in lipL32. The remaining 46 isolates were resolved into 21 sequence types (STs) by 7L, and 30 genotypes by 6L. Overall nucleotide diversity (based on concatenated sequence) was 3.6% and 2.3% for 7L and 6L, respectively. The D value (discriminatory ability) of 7L and 6L were comparable, i.e. 92.0 (95% CI 87.5-96.5) vs. 93.5 (95% CI 88.6-98.4). The dN/dS ratios calculated for each locus indicated that none were under positive selection. Neighbor joining trees were reconstructed based on the concatenated sequences for each scheme. Both trees showed two distinct groups corresponding to L. interrogans and L. kirschneri, and both identified two clones containing 10 and 7 clinical isolates, respectively. There were six instances in which 6L split single STs as defined by 7L into closely related clusters. We noted two discrepancies between the trees in which the genetic relatedness between two pairs of strains were more closely related by 7L than by 6L. CONCLUSIONS: This genetic analysis indicates that the two schemes are comparable. We discuss their practical advantages and disadvantages. PMID- 22087343 TI - Development and evaluation of a new lateral flow immunoassay for serodiagnosis of human fasciolosis. AB - BACKGROUND: Human fasciolosis is a re-emerging disease worldwide and is caused by species of the genus Fasciola (F. hepatica and F. gigantica). Human fasciolosis can be diagnosed by classical coprological techniques, such as the Kato-Katz test, to reveal parasite eggs in faeces. However, although 100% specific, these methods are generally not adequate for detection of acute infections, ectopic infections, or infections with low number of parasites. In such cases immunological methods may be a good alternative and are recommended for use in major hospitals where trained personnel are available, although they are not usually implemented for individual testing. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a new lateral flow test (SeroFluke) for the serodiagnosis of human fasciolosis. The new test was constructed with a recombinant cathepsin L1 from F. hepatica, and uses protein A and mAb MM3 as detector reagents in the test and control lines, respectively. In comparison with an ELISA test (MM3-SERO) the SeroFluke test showed maximal specificity and sensitivity and can be used with serum or whole blood samples. CONCLUSIONS/SIGNIFICANCE: The new test can be used in major hospitals in hypoendemic countries as well as in endemic/hyperendemic regions where point-of-care testing is required. PMID- 22087345 TI - Fatal attraction phenomenon in humans: cat odour attractiveness increased for toxoplasma-infected men while decreased for infected women. AB - BACKGROUND: Latent toxoplasmosis, a lifelong infection with the protozoan Toxoplasma gondii, has cumulative effects on the behaviour of hosts, including humans. The most impressive effect of toxoplasmosis is the "fatal attraction phenomenon," the conversion of innate fear of cat odour into attraction to cat odour in infected rodents. While most behavioural effects of toxoplasmosis were confirmed also in humans, neither the fatal attraction phenomenon nor any toxoplasmosis-associated changes in olfactory functions have been searched for in them. PRINCIPAL FINDINGS: Thirty-four Toxoplasma-infected and 134 noninfected students rated the odour of urine samples from cat, horse, tiger, brown hyena and dog for intensity and pleasantness. The raters were blind to their infection status and identity of the samples. No signs of changed sensitivity of olfaction were observed. However, we found a strong, gender dependent effect of toxoplasmosis on the pleasantness attributed to cat urine odour (p = 0.0025). Infected men rated this odour as more pleasant than did the noninfected men, while infected women rated the same odour as less pleasant than did noninfected women. Toxoplasmosis did not affect how subjects rated the pleasantness of any other animal species' urine odour; however, a non-significant trend in the same directions was observed for hyena urine. CONCLUSIONS: The absence of the effects of toxoplasmosis on the odour pleasantness score attributed to large cats would suggest that the amino acid felinine could be responsible for the fatal attraction phenomenon. Our results also raise the possibility that the odour specific threshold deficits observed in schizophrenia patients could be caused by increased prevalence of Toxoplasma-infected subjects in this population rather than by schizophrenia itself. The trend observed with the hyena urine sample suggests that this carnivore, and other representatives of the Feliformia suborder, should be studied for their possible role as definitive hosts in the life cycle of Toxoplasma. PMID- 22087346 TI - Adequate wound care and use of bed nets as protective factors against Buruli Ulcer: results from a case control study in Cameroon. AB - BACKGROUND: Buruli ulcer is an infectious disease involving the skin, caused by Mycobacterium ulcerans. Its exact transmission mechanism remains unknown. Several arguments indicate a possible role for insects in its transmission. A previous case-control study in the Nyong valley region in central Cameroon showed an unexpected association between bed net use and protection against Buruli ulcer. We investigated whether this association persisted in a newly discovered endemic Buruli ulcer focus in Bankim, northwestern Cameroon. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control study on 77 Buruli ulcer cases and 153 age , gender- and village-matched controls. Participants were interviewed about their activities and habits. Multivariate conditional logistic regression analysis identified systematic use of a bed net (Odds-Ratio (OR) = 0.4, 95% Confidence Interval [95%CI] = [0.2-0.9], p-value (p) = 0.04), cleansing wounds with soap (OR [95%CI] = 0.1 [0.03-0.3], p<0.0001) and growing cassava (OR [95%CI] = 0.3 [0.2 0.7], p = 0.005) as independent protective factors. Independent risk factors were bathing in the Mbam River (OR [95%CI] = 6.9 [1.4-35], p = 0.02) and reporting scratch lesions after insect bites (OR [95%CI] = 2.7 [1.4-5.4], p = 0.004). The proportion of cases that could be prevented by systematic bed net use was 32%, and by adequate wound care was 34%. CONCLUSIONS/SIGNIFICANCE: Our study confirms that two previously identified factors, adequate wound care and bed net use, significantly decreased the risk of Buruli ulcer. These associations withstand generalization to different geographic, climatic and epidemiologic settings. Involvement of insects in the household environment, and the relationship between wound hygiene and M. ulcerans infection should now be investigated. PMID- 22087344 TI - Induction of CD4(+)CD25(+)FOXP3(+) regulatory T cells during human hookworm infection modulates antigen-mediated lymphocyte proliferation. AB - Hookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from elimination and minimizing severe host pathology. While several mechanisms may be involved in the immunomodulation by parasitic infection, experimental evidences have pointed toward the possible involvement of regulatory T cells (Tregs) in downregulating effector T-cell responses upon chronic infection. However, the role of Tregs cells in human hookworm infection is still poorly understood and has not been addressed yet. In the current study we observed an augmentation of circulating CD4(+)CD25(+)FOXP3(+) regulatory T cells in hookworm-infected individuals compared with healthy non-infected donors. We have also demonstrated that infected individuals present higher levels of circulating Treg cells expressing CTLA-4, GITR, IL-10, TGF-beta and IL-17. Moreover, we showed that hookworm crude antigen stimulation reduces the number of CD4(+)CD25(+)FOXP3(+) T regulatory cells co-expressing IL-17 in infected individuals. Finally, PBMCs from infected individuals pulsed with excreted/secreted products or hookworm crude antigens presented an impaired cellular proliferation, which was partially augmented by the depletion of Treg cells. Our results suggest that Treg cells may play an important role in hookworm induced immunosuppression, contributing to the longevity of hookworm survival in infected people. PMID- 22087347 TI - Unusual dengue virus 3 epidemic in Nicaragua, 2009. AB - The four dengue virus serotypes (DENV1-4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009-January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009-10, compared to 13-65 cases in 2004-9. In both studies, significantly more patients experienced "compensated shock" (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009-10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1-2 days) in 2009-10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years - similar to the cohort study. DENV-3 predominated in 2008-9, 2009-10, and 2010-11, and full-length sequencing revealed no major genetic changes from 2008-9 to 2010-11. In 2008-9 and 2010-11, typical dengue was observed; only in 2009-10 was unusual presentation noted. Multivariate analysis revealed only "2009-10" as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1 2009 antibodies. This study demonstrates that parameters other than serotype, viral genomic sequence, immune status, and sequence of serotypes can play a role in modulating dengue disease outcome. PMID- 22087348 TI - Evaluation of the traditional and revised WHO classifications of Dengue disease severity. AB - Dengue is a major public health problem worldwide and continues to increase in incidence. Dengue virus (DENV) infection leads to a range of outcomes, including subclinical infection, undifferentiated febrile illness, Dengue Fever (DF), life threatening syndromes with fluid loss and hypotensive shock, or other severe manifestations such as bleeding and organ failure. The long-standing World Health Organization (WHO) dengue classification and management scheme was recently revised, replacing DF, Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) with Dengue without Warning Signs, Dengue with Warning Signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) and Severe Dengue (SD; dengue with severe plasma leakage, severe bleeding, or organ failure). We evaluated the traditional and revised classification schemes against clinical intervention levels to determine how each captures disease severity using data from five years (2005-2010) of a hospital-based study of pediatric dengue in Managua, Nicaragua. Laboratory-confirmed dengue cases (n = 544) were categorized using both classification schemes and by level of care (I-III). Category I was out-patient care, Category II was in-patient care that did not meet criteria for Category III, which included ICU admission, ventilation, administration of inotropic drugs, or organ failure. Sensitivity and specificity to capture Category III care for DHF/DSS were 39.0% and 75.5%, respectively; sensitivity and specificity for SD were 92.1% and 78.5%, respectively. In this data set, DENV-2 was found to be significantly associated with DHF/DSS; however, this association was not observed with the revised classification. Among dengue-confirmed cases, the revised WHO classification for severe dengue appears to have higher sensitivity and specificity to identify cases in need of heightened care, although it is no longer as specific for a particular pathogenic entity as was the traditional schema. PMID- 22087349 TI - [Atrial fibrillation, frequency, etiologic factors, evolution and treatment in a cardiology department in Dakar, Senegal]. PMID- 22087350 TI - [Surgical complications of renal transplantation from living donors: experience of the CHU Ibn Sina, Rabat]. PMID- 22087351 TI - Application of potential outcomes to an intentional weight loss latent variable problem. AB - Studies that explore the link between weight loss among obese individuals and mortality have met with mixed results. One possible explanation is that total weight loss may have contributions from weight loss that is intentional and weight loss that is unintentional. The latter may be due to some underlying condition that has a deleterious effect on subsequent mortality. Some studies have then focused on subjects who intend to lose weight. However, in a population there is no guarantee that weight loss among these individuals is due only to their intention. This paper extends the work of Coffey et al., (2005) who treated intentional weight loss as a latent variable. In particular, the problem is reformulated using potential outcomes. This formulation more clearly identifies a nonestimable correlation that arises because of the latent variable, and it allows for the incorporation of covariate information that can tighten estimable bounds for this correlation. We show in a data set from an experiment on mice that substantial tightening of bounds is possible with a covariate that is predictive of weight loss. These bounds can then, in turn, be used to estimate bounds on a causal parameter in a linear model. PMID- 22087352 TI - In Vitro Assessment of Apoptosis and Necrosis Following Cold Storage in a Human Airway Cell Model. AB - As advances in medical technology improve the efficacy of cell and tissue transplantation, a void remains in our knowledge base as to the specific molecular responses of cells to low-temperature storage. While much focus has been given to solution formulation for tissue perfusion during storage, investigations into cold exposure-induced complex molecular changes remain limited. The intent of this study was to quantify the levels of cell death following hypothermic storage in a lung cell model, establishing a foundation for future in-depth molecular analysis. Normal human lung fibroblasts (IMR-90) were stored for 1 day or 2 days and small airway epithelial cells (SAEC) were stored for 5 days or 7 days at 4 degrees C in complete media, ViaSpan, or ViaSpan + pan caspase (VI) inhibitor. (Poststorage viability was assessed for 3 days using alamarBlue(TM).) Sample analysis revealed that IMR-90 cells stored in ViaSpan remained 80% (+/-9) viable after 1 day of storage and 21% (+/-7) viable after 2 days of storage. SAEC cells stored in ViaSpan remained 81% (+/-5) viable after 5 days and 28% (+/-7) after 7 days. Microfluidic flow cytometry analysis of the apoptotic and necrotic populations in the ViaSpan-stored samples revealed that in the IMR-90 cells stored for 2 days, 7% of the population was apoptotic at 4-h poststorage, while ~70% was identified as necrotic. Analysis of the SAEC cell system following 7 days of ViaSpan storage revealed an apoptotic peak of 19% at 4 h poststorage and a corresponding necrotic peak of 19%. Caspase inhibition during hypothermic storage increased viability 33% for IMR-90 and 25% for SAEC. Data revealed a similar pattern of cell death, through both apoptosis and necrosis, once the onset of cold storage failure began, implying a potential conserved mechanism of cold-induced cell death. These data highlight the critical need for a more in-depth understanding of the molecular changes that occur as a result of cold exposure in cells and tissues. PMID- 22087353 TI - Biobank Recruitment: Motivations for Nonparticipation. AB - Molecular data, essential for genomics research, can be captured more efficiently in large-scale, population-based biobanks of genetic material rather than by individual studies. Biobanks also offer improved quality and reliability of genetic samples and access through automated sample retrieval. However, it is challenging to adequately inform participants of the broad nature of the research and participation risks and benefits. In addition, recent studies suggest concerns about data sharing and return of research results, or future research topics (eg, stereotypical or potentially stigmatizing traits). We evaluated the interest in participating in a biobank and reasons for nonparticipation. PMID- 22087354 TI - A defect in the activities of Delta and Delta desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-alpha (TNF-alpha) and TNF receptor 1 transcripts and serum TNF-alpha levels are increased and IL-6( /-) mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E(2) (PGE(2)). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-alpha and PGE(2) production. These results suggest that the activities of Delta(6) and Delta(5) desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and alpha-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti inflammatory molecules, LXs, resolvins and protectins that could pre vent NAFLD. This suggests that an imbalance between pro- and anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD. PMID- 22087355 TI - Disordered eating behaviors in type 1 diabetic patients. AB - Patients with type 1 diabetes mellitus are at high risk for disordered eating behaviors (DEB). Due to the fact that type 1 diabetes mellitus is one of the most common chronic illnesses of childhood and adolescence, the coexistence of eating disorders (ED) and diabetes often affects adolescents and young adults. Since weight management during this state of development can be especially difficult for those with type 1 diabetes, some diabetics may restrict or omit insulin, a condition known as diabulimia, as a form of weight control. It has been clearly shown that ED in type 1 diabetics are associated with impaired metabolic control, more frequent episodes of ketoacidosis and an earlier than expected onset of diabetes-related microvascular complications, particularly retinopathy. The management of these conditions requires a multidisciplinary team formed by an endocrinologist/diabetologist, a nurse educator, a nutritionist, a psychologist and, frequently, a psychiatrist. The treatment of type 1 diabetes patients with DEB and ED should have the following components: diabetes treatment, nutritional management and psychological therapy. A high index of suspicion of the presence of an eating disturbance, particularly among those patients with persistent poor metabolic control, repeated episodes of ketoacidosis and/or weight and shape concerns are recommended in the initial stage of diabetes treatment, especially in young women. Given the extent of the problem and the severe medical risk associated with it, more clinical and technological research aimed to improve its treatment is critical to the future health of this at-risk population. PMID- 22087356 TI - Consequences of gestational and pregestational diabetes on placental function and birth weight. AB - Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulder dystocia, hypoglycemia and respiratory distress). The fetoplacental impairment and intrauterine programming of diseases in the offspring's later life induced by gestational diabetes are similar to those induced by type 1 and type 2 diabetes mellitus. Despite the existence of several developmental and morphological differences in the placenta from rodents and women, there are similarities in the alterations induced by maternal diabetes in the placenta from diabetic patients and diabetic experimental models. From both human and rodent diabetic experimental models, it has been suggested that the placenta is a compromised target that largely suffers the impact of maternal diabetes. Depending on the maternal metabolic and proinflammatory derangements, macrosomia is explained by an excessive availability of nutrients and an increase in fetal insulin release, a phenotype related to the programming of glucose intolerance. The degree of fetal damage and placental dysfunction and the availability and utilisation of fetal substrates can lead to the induction of macrosomia or intrauterine growth restriction. In maternal diabetes, both the maternal environment and the genetic background are important in the complex and multifactorial processes that induce damage to the embryo, the placenta, the fetus and the offspring. Nevertheless, further research is needed to better understand the mechanisms that govern the early embryo development, the induction of congenital anomalies and fetal overgrowth in maternal diabetes. PMID- 22087357 TI - Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats. AB - AIM: To study the combinative effects of nanocerium and selenium in a murine model of diabetes. METHODS: Cerium oxide (CeO(2)) nanoparticles (60 mg/kg per day) and sodium selenite (5 MUmol/kg per day) alone or in combination, or the metal form of CeO(2) (60 mg/kg) were administered for 2 wk by intraperitoneal injection to streptozotocin-induced diabetic rats. At the end of treatment blood was collected, liver tissue dissected and then oxidative stress markers, extent of energy depletion and lipid profile were evaluated. RESULTS: Antioxidant enzymes and high density lipoprotein decreased whereas oxidative stress, adenosine diphosphate/adenosine triphospahte levels, cholesterol, triglyceride and low density lipoprotein increased on induction of diabetes. All were improved by a combination of nanocerium and sodium selenite. There was a relative amelioration by CeO(2) nanoparticles or sodium selenite alone, but the metal form of CeO(2) showed no significant improvement. CONCLUSION: The combination of nanocerium and sodium selenite is more effective than either alone in improving diabetes-induced oxidative stress. PMID- 22087359 TI - Interval from Prostate Biopsy to Robot-Assisted Laparoscopic Radical Prostatectomy (RALP): Effects on Surgical Difficulties. AB - PURPOSE: Traditionally, an interval of 4 to 6 weeks has been recommended after prostate biopsy before open radical prostatectomy. However, such an interval is not explicitly specified in robot-assisted laparoscopic radical prostatectomy (RALP). This study was designed to determine whether the interval from prostate biopsy to RALP affects surgical difficulties. MATERIALS AND METHODS: Between January 2008 and May 2009, a total of 237 men underwent RALP in our institution. The interval from biopsy to RALP was categorized as follows: <= 2 weeks, >2 to <= 4 weeks, >4 to <= 6 weeks, >6 to <= 8 weeks, and >8 weeks. Multivariate analysis was used to identify whether the interval from prostate biopsy to RALP was an independent predictor of operative time, estimated blood loss (EBL), margin positivity, continence, and potency. RESULTS: Among the 5 groups, there were no significant differences in age, body mass index (BMI), preoperative serum prostate-specific antigen (PSA), prostate volume, or preoperative International Index of Erectile Dysfunction-5 score (all p>0.05). In the multivariate analysis, operative time was significantly associated with prostate volume. EBL was associated with prostate volume and BMI. Margin positivity was associated with preoperative serum PSA, prostate volume, and biopsy Gleason score. Postoperative continence and potency were significantly associated with age. However, in univariate and multivariate analyses, the interval from biopsy to RALP was not significantly associated with operative time, EBL, margin positivity, postoperative continence, or potency (all p>0.05). CONCLUSIONS: Our data suggest that the interval from prostate biopsy to RALP is not related to surgical difficulties. PMID- 22087358 TI - Late-onset hypogonadism syndrome and lower urinary tract symptoms. AB - Androgen replacement therapy (ART) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism (LOH) syndrome. Concurrent with the progressive decline in testosterone from middle age, there is a gradual increase in prostate volume, reflecting the development of benign prostatic hyperplasia (BPH). Prostate growth is dependent on the presence of androgens, and conversely, antiandrogen agents or orchidectomy can decrease prostate volume in patients with BPH. Thus, it is important to investigate whether ART could have any negative effects on prostatic disease or lower urinary tract symptoms (LUTS). Although only limited amounts of information on the correlations between androgen levels in aging men and clinical manifestations of LUTS are available, a few recent studies have suggested that testosterone levels may have some beneficial effects on various urinary functions in men. Androgen receptors are found in the urothelium, urinary bladder, prostate, and urethra, and testosterone could have an impact on the autonomic nervous system, bladder smooth muscle differentiation, nitric oxide synthase, phosphodiesterase-5 and Rho/Rho-kinase activities, and pelvic blood flow. In addition, some previous studies demonstrated that ART had little effect on LUTS or urinary function in aging men with LOH syndrome. Furthermore, some recent randomized controlled trials indicated that short-term ART may be effective in the improvement of LUTS in hypogonadal men with mild BPH. However, only limited information is available regarding the effects of longer term ART or the safety of ART in men with severe BPH and LUTS, and further studies are required to reach more definitive conclusions. PMID- 22087360 TI - Prognostic factors and clinical outcomes of urological soft tissue sarcomas. AB - PURPOSE: The purpose of this study was to elucidate prognostic factors for survival and clinical outcomes of rological soft tissue sarcomas (STSs). MATERIALS AND METHODS: This was a retrospective review of the medical records of 48 patients with urological STS treated from January 1982 to July 2009. Demographic and pathological characteristics were compared. Patients' demographics, clinico-pathological parameters, overall survival, and the factors expected to predict survival, such as sex, age at diagnosis, primary organ, surgical resection, metastasis, and mass size, were analyzed. We evaluated differences in survival on the basis of histological subtype by Kaplan-Meier analysis and multivariate Cox proportional hazards regression. RESULTS: The study included 34 males (70.8%) and 14 females (29.1%). The mean age at diagnosis was 47.1 years (range, 3 to 80). The most common site was the retroperitoneum (n=16), followed by the kidney (n=12), prostate (n=10), bladder (n=7), ureter (n=1), and paratesticular region (n=1). Nineteen patients (39.5%) had other organ metastases at diagnosis. The most common subtypes of sarcoma were leiomyosarcoma (50%), rhabdomyosarcoma (18.7%), and liposarcoma (8%). The remaining 11 cases had other histological subtypes (22.9%). Mean tumor size was 9.5 cm (range, 2.2 to 24). Thirty-three patients (68.7%) underwent surgical resection. The overall survival rate at 5 years was 51.4%. In the univariate and multivariate analysis, surgical resection, primary tumor site, and metastasis at diagnosis remained significant predictors of prognosis. Patients with retroperitoneal sarcoma had a higher overall survival rate by 5 years compared with patients with other organ sarcoma. CONCLUSIONS: The overall survival rate at 5 years was 51.4%. Surgical resection, primary tumor site, and metastasis at diagnosis remained significant predictors of prognosis. PMID- 22087361 TI - Effect of Prostate Biopsy Hemorrhage on MRDW and MRS Imaging. AB - PURPOSE: To retrospectively evaluate the effect of post-prostate-biopsy hemorrhage on the interpretation of magnetic resonance diffusion-weighted (MRDW) and magnetic resonance spectroscopic (MRS) imaging in the detection of prostate cancer. We also investigated the optimal timing for magnetic resonance examination after prostate biopsy. MATERIALS AND METHODS: We reviewed the records of 135 men. All patients underwent prostate magnetic resonance imaging (MRI). The prostate was divided into eight regions according to the biopsy site. Subsequently, we measured hemorrhage on apparent diffusion coefficient (ADC) values and (choline+creatinine)/citrate ([Cho+Cr]/Cit) ratios in the same regions on the MRI. We investigated the effect of hemorrhage at ADC values and (Cho+Cr)/Cit ratios on MRI and the relationship between prostate biopsy results and MRI findings. RESULTS: The mean patient age was 68.7 years and the mean time between biopsy and MRI was 23.5 days. The total hemorrhagic score demonstrated no significant associations with intervals from biopsy to MRI. Higher hemorrhagic scores were associated with higher ADC values, prostate cancer, and noncancer groups, respectively (p<0.001). ADC values were lower in tumors than in normal tissue (p<0.001), and ADC values were inversely correlated with tumor Gleason score in biopsy cores (p<0.001). However, (Cho+Cr)/Cit ratios did not exhibit any association with prostate biopsy results and hemorrhage. CONCLUSIONS: Hemorrhage had no significant associations with the interval from biopsy to MRI. ADC values may help to detect prostate cancer and predict the aggressiveness of cancer; however, it is important to consider the bias effect of hemorrhage on the interpretation of MRDW imaging given that hemorrhage affects ADC values. PMID- 22087362 TI - Effect of Shifting from Combination Therapy to Monotherapy of alpha-Blockers or 5alpha-Reductase Inhibitors on Prostate Volume and Symptoms in Patients with Benign Prostatic Hyperplasia. AB - PURPOSE: Combination therapy of alpha-blockers and 5alpha-reductase inhibitors (5 ARIs) is widely used for the treatment of benign prostatic hyperplasia (BPH). We aimed to study the effect on prostate volume and symptoms of shifting to monotherapy in patients who previously received a combination therapy. MATERIALS AND METHODS: A prospective study was conducted of 60 patients who were diagnosed with BPH. Patients were aged 45 years or older and had a prostate volume of 30 cc or more, International Prostate Symptom Score (IPSS) of 12 or above, maximal flow rate (Qmax) of 15 ml/s or less, and prostate-specific antigen (PSA) level of less than 10 ng/ml. The patients initially received a combination therapy of doxazosin 4 mg/day and finasteride 5 mg/day for 3 months and were then randomly assigned to receive monotherapy for 3 months. The factors were then compared. RESULTS: A total of 30 patients were assigned to doxazosin (group 1) and 30 to finasteride (group 2) after the combination therapy. The percentage changes in prostate volume, IPSS, and Qmax during the period from post-combination therapy to post monotherapy were not significantly different between the two groups (p=0.052, 0.908, 0.081), whereas PSA significantly decreased in group 2 (p<0.001). IPSS was not significantly different at post-combination therapy and at post-monotherapy in both groups (p=0.858, 0.071). The prostate volume significantly increased from 40.97 cc at post-combination therapy to 44.29 cc at post-monotherapy in group 1 (p=0.001) and insignificantly increased from 38.32 cc to 38.61 cc in group 2 (p=0.696). CONCLUSIONS: Although the duration of drug administration was short in this study, 5-ARI monotherapy could maintain the alleviated symptoms and reduce the risk of acute urinary retention and surgery due to prostate regrowth in BPH patients whose symptoms improved with combination therapy. PMID- 22087363 TI - Relationship between Proximal Urethrovaginal Space Thickness and Detrusor Overactivity in Women with Stress Urinary Incontinence. AB - PURPOSE: Detrusor overactivity (DO) cannot be predicted by clinical symptoms. Although it is possible that DO could be related to anatomical structures, scanty data exist about the relations between DO and anatomical structures. The aim of this study was to investigate anatomical differences in DO by measuring the thickness of the urethrovaginal space (UVS) and the urethral length (UL) in women with stress urinary incontinence (SUI). MATERIALS AND METHODS: Prospective data were collected from 72 women with SUI who underwent the midurethral sling operation. The subjects were divided into 2 groups according to the presence of DO by preoperative urodynamic study (UDS). UVS thickness was measured by trans vaginal ultrasound. UL was measured by using a urethral catheter and a ruler. UVS thickness, UL, Q-tip, and urodynamic parameters, such as maximal urethral closure pressure (MUCP) and Valsalva leak point pressure, were compared between the two groups. RESULTS: Of 72 women, 23 patients had DO (31.9%). The proximal UVS was significantly thinner (p<0.001) and the MUCP was significantly lower (p=0.008) in women with DO. According to the receiver operating characteristic (ROC) curve based DO prediction, the best cutoff value for UVS thickness was 0.84 cm (area under the ROC curve 0.763). CONCLUSIONS: In this study, the proximal UVS was significantly thinner and the MUCP was significantly lower in patients with DO. A proximal UVS thickness of less than 0.84 cm was shown to be a predictive parameter for the development of DO on preoperative UDS. A large-scale prospective study is needed to validate these results. PMID- 22087364 TI - Percutaneous decortication of cystic renal disease. AB - PURPOSE: To assess the efficacy of percutaneous unroofing in the treatment of simple renal cysts instead of laparoscopic decortication and open surgeries. MATERIALS AND METHODS: From November 2009 to October 2010 at our department, 11 patients with 12 simple cyst units were managed by percutaneous unroofing. All cysts were evaluated with ultrasonography and abdominal computed tomography. If there were no contraindications, cyst wall resection was performed. A standard transurethral resectoscope was used to resect the cyst wall, and the parenchymal portion of the cyst was subsequently cauterized. The drain was left in place for 2 days. RESULTS: At the 5-month follow-up, patients were asked about their symptoms and ultrasonography was performed. From 12 cyst units, 8 were completely resolved, 3 were reduced to less than 50%, and 1 was persistent to near its original size. Success was defined as a more than 50% reduction in cyst volume. CONCLUSIONS: Simple renal cysts can be safely managed by percutaneous unroofing with a success rate of more than 90%. This technique can offer several advantages over open surgery, such as decreased length of hospital stay, improved convalescence, and reduced risk of complications. Percutaneous resection also avoids the multiple trocar sites, extensive dissection, and technical difficulty associated with laparoscopy. PMID- 22087365 TI - Comparison of an Indwelling Period Following Ureteroscopic Removal of Stones between Double-J Stents and Open-Ended Catheters: A Prospective, Pilot, Randomized, Multicenter Study. AB - PURPOSE: The aim of this study was to evaluate whether long-term, postoperative ureteral stenting is necessary after ureteroscopic removal of stones (URS) during an uncomplicated surgical procedure. MATERIALS AND METHODS: We prospectively examined 54 patients who underwent URS for lower ureteral stones from February 2010 to October 2010. Inclusion criteria were a stone less than 10 mm in diameter, absence of ureteral stricture, and absence of ureteral injury during surgery. We randomly placed 5 Fr. open-tip ureteral catheters in 26 patients and removed the Foley catheter at postoperative day 1. The remaining 28 patients received double-J stents that were removed at postoperative day 14 by cystoscopy under local anesthesia. All patients provided visual analogue scale (VAS) pain scores at postoperative days 1, 7, and 14 and completed the storage categories of the International Prostate Symptom Score (IPSS) at postoperative day 7. RESULTS: The VAS scores were not significantly different on postoperative day 1 but were significantly smaller in the 1-day ureteral catheter group at postoperative days 7 and 14 (p<0.01). All of the storage categories of the IPSS were significantly lower in the 1-day ureteral stent group (p<0.01). The ratio of patients who needed intravenous analgesics because of severe postoperative flank pain was not significantly different between the two groups (p=0.81). No patients experienced severe flank pain after postoperative day 2, and no patients in either group had any other complications. CONCLUSIONS: One-day ureteral catheter placement after URS can reduce postoperative pain and did not cause specific complications compared with conventional double-J stent placement. PMID- 22087366 TI - The prevalence and clinical significance of urethritis and cervicitis in asymptomatic people by use of multiplex polymerase chain reaction. AB - PURPOSE: Our purpose was to conduct a screening test for urethritis or cervicitis as a sexually transmitted disease (STD) by using multiplex polymerase chain reaction(PCR) and to determine the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis in asymptomatic people. MATERIALS AND METHODS: From July 2010 to December 2010, 709 persons who came to the hospital for a general checkup were tested. Multiplex PCR assays were done with first voided urine samples or endocervical swabs by use of the Seeplex(r) STD6 ACE Detection kit. RESULTS: The mean age in this study was 45.4+/-8.1 years. Among the 709 persons, 229 (32.3%) had a positive result for at least one microorganism, 48 (6.8%) had two different species, 6 (0.8%) had three different species, and 1 person had four different species. The overall prevalence of asymptomatic STDs such as urethritis or cervicitis was 7.1% (50/709). The prevalence rates of chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis infection in asymptomatic persons were 5.6% (40/709), 0.4% (3/709), 0.3% (2/709), 22.1% (157/709), 11.6% (82/709), and 1.1% (8/709), respectively. CONCLUSIONS: With only a single sample, we could identify the prevalence rates of six microorganisms and the overall proportion of urethritis or cervicitis in asymptomatic people. This proportion cannot be neglected; therefore, screening tests for sexually transmitted diseases such as urethritis or ervicitis should be recommended to asymptomatic people. PMID- 22087367 TI - Impact of a retrotrigonal layer backup stitch on post-prostatectomy incontinence. AB - PURPOSE: To evaluate the impact of a retrotrigonal layer backup stitch (RTBS) during robot-assisted laparoscopic radical prostatectomy (RALP) on post prostatectomy incontinence. MATERIALS AND METHODS: We compared the difference in continence recovery between 94 patients (group 1, as historical controls) and 57 patients (group 2). The only technical difference between our two groups was the incorporation of the retrotrigonal layer into the posterior aspect of the vesicourethral anastomosis (group 1: without RTBS; group 2: with RTBS). Postoperative continence recovery was defined as the use of no absorbent pads. RESULTS: In group 1, the continence rate at 3, 6, and 12 months postoperatively was 40.4%, 70.2%, and 90.4%, respectively;in group 2, the continence rate was 42.1%, 70.1%, and 89.7%, respectively. The median (95% confidence interval) time to continence recovery was four months (range, 1 to 12 months) in group 1 and four months (range, 1 to 9 months) in group 2. Kaplan-Meier curves showed no significant difference in the recovery of continence between the two groups (log rank test, p=0.629). CONCLUSIONS: A RTBS does not appear to improve urinary incontinence after RALP. Further anatomical study and prospective randomized studies will be needed to confirm this. PMID- 22087368 TI - Unusual presentation of bilateral adrenocortical carcinoma mimicking adrenal metastasis. AB - A 75-year-old female visited our hospital with bilateral adrenal masses that were detected incidentally during lumbar spine magnetic resonance imaging (MRI) for the evaluation of radiating flank pain. Consecutive computed tomography and MRI revealed bilateral adrenal masses with no evidence of lymph node enlargement or local invasion; 2[(18)F]fluoro-2-deoxyglucose (FDG)-positron emission tomography showed an intense FDG accumulation in both adrenal glands without abnormal FDG uptake in extra-adrenal regions. The laboratory test results were within normal ranges. We performed a bilateral adrenalectomy. The pathologic diagnosis of both adrenal masses was consistent with adrenocortical carcinoma. The patient recovered well with no complications. PMID- 22087369 TI - Solitary testicular metastasis of prostate cancer mimicking primary testicular cancer. AB - We report a rare case of testicular metastasis from prostate cancer. A 68-year old patient presented with a right testicular mass with discomfort. He had a history of robot-assisted laparoscopic radical prostatectomy and had received adjuvant radiation therapy and had been treated with androgen deprivation therapy continuously at another institution. We performed a right inguinal orchiectomy. The testicular mass was diagnosed as a metastasis from prostate carcinoma. PMID- 22087370 TI - Erratum: pT3 Predictive Factors in Patients with a Gleason Score of 6 in Prostate Biopsies. AB - [This corrects the article on p. 598 in vol. 52, PMID: 22025953.]. PMID- 22087371 TI - Acute Coronary Syndrome, Diabetes and Hypertension: Oman must pay more attention to chronic non-communicable diseases. PMID- 22087372 TI - Shaken baby syndrome as a form of abusive head trauma. AB - Shaken baby syndrome (SBS) is a form of abuse that is characterised by brain injury. Because of the subtle and yet debilitating neurobehavioural impairment which ensues, SBS represents a diagnostic dilemma for attending clinicians. The situation is made worse by the young age of the affected child who may not be capable of explaining what happened. SBS has been reported in many parts of the world. To our knowledge, there is a dearth of literature on the topic from Arab/Islamic countries. This article attempts to shed light on the syndrome by reviewing information on the aetiology of SBS, as well as on its diagnosis and the reasons for delayed diagnosis. The central aim of this review is to increase awareness of SBS so that enlightened policies for prevention and intervention could be developed in the region and particularly in Oman. PMID- 22087373 TI - Health care market deviations from the ideal market. AB - A common argument in the health policy debate is that market forces allocate resources efficiently in health care, and that government intervention distorts such allocation. Rarely do those making such claims state explicitly that the market they refer to is an ideal in economic theory which can only exist under very strict conditions. This paper explores the strict conditions necessary for that ideal market in the context of health care as a means of examining the claim that market forces do allocate resources efficiently in health care. PMID- 22087374 TI - Acute coronary syndrome in oman: results from the gulf registry of acute coronary events. AB - Acute coronary syndrome (ACS) is the most common cause of cardiovascular mortality and morbidity in Western countries. International guidelines for diagnosis and treatment have been developed based on randomised clinical trials. However, data from international registries report a lack of association between guideline recommendations and actual clinical practice. Similarly, the Gulf Heart Association initiated a registry called Gulf Registry of Acute Coronary Events (Gulf RACE). This registry was developed to determine the characteristics and management of ACS in the Gulf countries including Oman. Here, we report on the results of the various Gulf RACE registry studies from Oman and compare our results with the main Gulf RACE data as well as other international registries. PMID- 22087375 TI - Diabetes Care in Oman: Obstacles and solutions. AB - Diabetes has become one of the most challenging chronic diseases with its prevalence increasing in most countries worldwide. The Arabian Gulf countries face a similar increasing prevalence of diabetes. Diabetes care requires not only the support of the health authorities, but the contribution of all the sectors of the community and requires good financial support. In Oman, there are many factors which affect the care of diabetes. In this article, these factors are addressed and recommended solutions discussed. PMID- 22087377 TI - A Novel Splice-site Allelic Variant is Responsible for Wilson Disease in an Omani Family. AB - OBJECTIVES: The objective of this study was to characterise Wilson's Disease (WD) [OMIM 277900] genetically and test for allelic variants in the copper transport gene (ATPase, Cu(++) transporting, beta polypeptide, ATP7B) responsible for the disease in an Omani family. METHODS: Three index patients from an Omani family had been previously diagnosed with WD. All three patients suffered neurological symptoms and signs. Forty-six relatives in the family were screened for WD. Eleven more individuals were positive, but asymptomatic. RESULTS: Thirteen non disease-causing allelic gene variants, described previously, were identified in the ATP7B gene from 46 family members. A putative novel disease-causing splice site variant (c.2866-2A>G), which has not been reported previously, was detected in this family. It is located upstream of exon 13 which encodes part of transmembrane copper channel (Ch/Tm6). Reverse transcription polymerase chain reaction was used to amplify a complementary DNA (cDNA) fragment containing exons 12, 13 and 14. Exon 13 was entirely skipped from the transcript which probably would result in a defective ATP7B protein. CONCLUSION: A new ATP7B splice-site allelic variant, found among the 14 WD patients segregated with the disease in a recessive manner, suggests it is a disease-causing variant. PMID- 22087376 TI - Prevalence of uncontrolled hypertension in primary care settings in Al seeb wilayat, oman. AB - OBJECTIVES: This study aimed to estimate the prevalence of uncontrolled hypertension (HTN) among Omani hypertensive patients, on treatment and under primary health care (PHC) follow-up in Al Seeb Wilayat, Oman. Socio-demographic and clinical factors were explored for possible influence on blood pressure (BP) control. METHODS: Based on an assumption of 50% prevalence of uncontrolled HTN, a retrospective data collection was conducted on the last three follow-up visits of 411 randomly selected Omani adults (>=18 years) from 3,459 hypertensive patients. Adequate BP control was defined using criteria from 7(th) Report of the Joint National Committee on Prevention Detection Evaluation & Treatment of High Blood Pressure (JNC-7). A P value of <0.05 and odds ratios with 95% confidence interval were used to assess for association. RESULTS: The targets for adequate BP control were achieved in 39% of the studied patients (95% confidence interval [CI]: 34 44%). Lower BP control was found among hypertensives with diabetes (6.4%, P = <0.001) and renal disease (18.5%, P = 0.02); those with cardiovascular disease (CVD) showed relatively better control (58%). Age and gender had no impact on BP control. Most patients were only on one (24%) or two (47%) antihypertensive medications, the most frequently used being beta-blockers (58.2%) and diuretics (56.3%). CONCLUSION: HTN is not adequately controlled in over 60% of treated patients; the presence of co-morbidity and less than aggressive treatment are significant contributors. Improving the quality of HTN care is a priority; effective efforts should be undertaken to improve BP control. PMID- 22087378 TI - Gender difference in relationship of apnoea/hypopnoea index with body mass index and age in the omani population. AB - OBJECTIVES: Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a disorder characterised by repetitive upper airway collapse during sleep in association with daytime sleepiness. It has an estimated prevalence of 2% and 4% among middle aged women and men respectively. The aim of the study was to look at the association of body mass index (BMI), age and gender and prevalence of OSAHS in the Omani population. METHODS: Polysomnography reports and hospital medical records of all patients who took part in the Sleep Study at the Sleep Laboratory of the Clinical Physiology Department, Sultan Qaboos University Hospital, between January 1995 and December 2006, were retrospectively reviewed. Data from both sources was gathered and analysed. RESULTS: A total of 1,042 sleep studies were conducted with 608 valid studies for analysis. The study showed that the apnoea/hypopnoea index (AHI) >15 was more prevalent in men compared to women (47.9% versus 33.5%, P = 0.001). There was significant correlation of AHI with BMI (P <0.0001) among men compared to women (P = 0.1); however, age was significantly correlated with AHI among women (P <0.0001), but not with men (P = 0.1). CONCLUSION: The results indicate that there is a gender difference in the prevalence of OSAHS and obesity is a major risk factor for OSAHS among Omani men whereas age is found to be a risk factor for OSAHS among women. PMID- 22087379 TI - Intra-Operative Neural Response Telemetry and Acoustic Reflex Assessment using an Advance-In-Stylet Technique and Modiolus-Hugging: A prospective cohort study. AB - OBJECTIVES: The development of cochlear implant (CI) electrode arrays has focused on the use of a minimally invasive technique involving a modiolus-hugging placement of the electrode. The aim of this study was to evaluate the "advance-in stylet" (AIS) technique compared to the advance-off-stylet (AOS) technique recommended for the current cochlear Nucleus((r)) device. In the AIS technique, the stylet is not removed. We evaluated the electrical auditory thresholds measured when the stylet was removed (modiolus-hugging) compared to measurements taken with the stylet in place (lateral wall cochlea electrode placement). METHODS: In this prospective cohort study, 30 consecutive patients received unilateral Nucleus Freedom((r)) CIs using AIS insertion. Measurement of the acoustic reflex (AR) and neural response telemetry (NRT) were performed with the stylet in place (lateral wall placement of the electrodes) and then removed (perimodiolar placement), and the results compared. The responses were measured in the basal, middle and apical turns in both groups-with and without stylet. RESULTS: The AIS surgery was completed without complication in 30 patients (16 males and 14 females, age range 3-54 years [mean 11]). Based on neural response telemetry, only apical electrodes showed statistically significant differences in thresholds, but the AR was not significantly different before or after stylet removal in any of the electrode groups tested. CONCLUSIONS: The effects of modiolus-hugging do not seem to result in a large difference in electrical stimulation thresholds so, in difficult cases, the stylet may be left in place without significantly changing the thresholds, except perhaps at the apical turn. PMID- 22087380 TI - Comparison of the Clinical Profile and Complications of Mixed Malarial Infections of Plasmodium Falciparum and Plasmodium Vivax versus Plasmodium Falciparum Mono infection. AB - OBJECTIVES: This study aimed to compare the clinical presentations and complications in patients having mixed malaria infection of Plasmodium falciparum and Plasmodium vivax with those of patients with malaria due to a P. falciparum mono-infection. METHODS: The medical records of malaria patients admitted to Kasturba Medical College, Manipal, India, during the years 2008-10 were analysed. Inclusion criteria were patients in whom P. falciparum and P. vivax coinfection or P. falciparum mono-infection alone was confirmed on peripheral smear examination. Exclusion criteria were patients in whom P. vivax infection alone was diagnosed on peripheral smear examination. The sample size was twenty patients diagnosed with mixed infection of P. falciparum and P. vivax and 60 patients diagnosed with P. falciparum mono-infection. RESULTS: 35% of mixed infections had thrombocytopenia as compared to 51.7% of P. falciparum mono infections. A total of 5% of the mixed infections had renal failure as compared to 16.7% of the falciparum mono-infections. Total bilirubin was raised in 15.8% of mixed infections and in 46.6% of falciparum mono-infections. Abnormal liver enzymes were seen in 36.8% of mixed infections and in 66.6% of falciparum mono infections. None of the mixed infections had a parasite index over 2% while it was present in 28% of the falciparum mono-infections. CONCLUSION: Patients with mixed infections were found to have a lower incidence of severe complications such as anaemia, thrombocytopenia, liver and renal dysfunction and a lower parasite index. Thus mixed malaria tends to have a more benign course as compared to malaria due to P. falciparum mono-infection. PMID- 22087381 TI - Perceptions and Attitudes of Medical Students towards Two Methods of Assessing Practical Anatomy Knowledge. AB - OBJECTIVES: Traditionally, summative practical examination in anatomy takes the form of 'spotters' consisting of a stream of prosections, radiological images and dissections with pins indicating specific structures. Recently, we have started to administer similar examinations online using the quiz facility in MoodleTM (a free, open-source web application for producing modular internet-based courses) in addition to the traditional format. This paper reports on an investigation into students' perceptions of each assessment environment. METHODS: Over a 3-year period, practical assessment in anatomy was conducted either in traditional format or online via learning management software called MoodleTM. All students exposed to the two examination formats at the College of Medicine & Health Sciences, Sultan Qaboos University, Oman, were divided into two categories: junior (Year 3) and senior (Year 4). An evaluation of their perception of both examination formats was conducted using a self-administered questionnaire consisting of restricted and free response items. RESULTS: More than half of all students expressed a clear preference for the online environment and believed it was more exam-friendly. This preference was higher amongst senior students. Compared to females, male students preferred the online environment. Senior students were less likely to study on cadavers when the examination was conducted online. Specimen quality, ability to manage time, and seating arrangements were major advantages identified by students who preferred the online format. CONCLUSION: Computer-based practical examinations in anatomy appeared to be generally popular with our students. The students adopted a different approach to study when the exam was conducted online as compared to the traditional 'steeplechase' format. PMID- 22087382 TI - Successful Use of Alternative Anticoagulants in the Management of Heparin-induced Thrombocytopenia with Thrombotic Complications: Report of 5 cases and review of literature. AB - Heparin is one of the most frequently used anticoagulants. It is easy to use, but can be associated with life-threatening side effects. One of these is heparin induced thrombocytopenia syndrome (HITS), which develops in about 3-5% of patients exposed to heparin and is associated with thrombosis in 1% of cases. We report here the successful treatment of five patients with HITS who were treated with alternative anticoagulants namely danaparoid or hirudin. The median time between their exposure to heparin and onset of symptoms and or signs was 10.2 days (range 7-14 days). Platelet counts decreased to a mean of 38.4 x 10(9) /l (12-82 x 10(9)/l). All five patients had evidence of thrombosis; four patients had clinical and radiological evidence of pulmonary emboli, one patient had confirmed deep vein thrombosis (DVT) and one patient had extensive skin necrosis of the thighs and abdomen. Platelet aggregation test were positive in two patients, inconclusive in one patient and negative in two patients. Two patients were anticoagulated with danaparoid and three with hirudin until their platelet counts returned to normal between 4 and 14 days (average 6 days) following the recognition of the syndrome. Our patients had significant morbidity, but no mortality. Immediate withdrawal of heparin is of paramount importance and introduction of alternative anticoagulant is necessary in the presence of thrombosis. PMID- 22087383 TI - Submyomatous Cornual Pregnancy: Managed surgically after failed medical management. AB - Cornual pregnancy constitutes an emergency while its diagnosis and management remain a challenge. Anatomical abnormalities in the uterus, such as fibroids in the cornual region, make the management even more difficult. A nulliparous patient presented with an ectopic pregnancy at the right cornua under a huge fibroid. Despite multiple doses of methotrexate for a cornual ectopic gestation, the serum beta human chorionic gonadotropin (beta-hcG) levels doubled on the fifth day and a viable fetus was demonstrated on imaging. Thus surgical intervention in the form of laparoscopy followed by laparotomy, myomectomy of a large cornual fibroid and cornuostomy was performed. The serum beta human chorionic gonadotropin result was negative three weeks later. Surgical intervention in the form of myomectomy and cornuostomy was necessary to preserve fertility in this unusual presentation of cornual ectopic pregnancy. PMID- 22087384 TI - Schwannoma of the Cervical Symphathetic Chain: First case report from Oman. AB - Schwannomas are benign, encapsulated and slow-growing nerve sheath tumours arising from Schwann cells. The schwannoma arising from the cervical sympathetic chain (SCSC) is a very rare tumour. It usually presents as a slow growing, painless and asymptomatic neck mass, hence preoperative clinical diagnosis is difficult. Radiological investigation and fine needle aspiration cytology make only a small contribution to its preoperative diagnosis, histopathological examination being much more useful. We report here the first case report of SCSC from Oman. It occurred in a 45 year-old female and was successfully excised. PMID- 22087385 TI - Late-onset Visual Loss in Osteopetrosis. AB - Late-onset visual loss is a complication of nerve entrapment and increased intracranial pressure. We hereby describe the first case in Eastern Africa. A 23 year-old lady presented with sudden blindness, headaches and body weakness. She had previously had treatment for multiple unexplained fractures. Findings of optic nerve entrapment explained this blindness. This case highlights the need to have a high index of suspicion in cases of unexplained fractures with late-onset blindness. PMID- 22087386 TI - Keystone design sliding skin flap for the management of small full thickness burns. AB - Deep dermal burns and full thickness burns are generally managed by excision and split thickness skin grafting. The skin graft may lead to unacceptable colour changes and be aesthetically unacceptable. Also, there may be a contour defect and, furthermore, it is followed by varying degrees of contracture. The keystone design sliding flap, first described in 2003, avoids the need for grafting and is not associated with any skin graft problems. We report two cases of the use of this flap as the primary surgery in reconstruction of small full thickness burn defects. PMID- 22087387 TI - Bilateral elastofibroma dorsi. PMID- 22087388 TI - Maternal Triglycerides: Underestimated predictors of neonatal birth weight. PMID- 22087389 TI - Re: vitamin d deficiency in omani women. PMID- 22087390 TI - Re: Improving Road Safety through Deterrence-Based Initiatives. PMID- 22087391 TI - Medical Tourism: Beneficence or maleficence? PMID- 22087392 TI - Blunt Cerebrovascular Injuries: A review of the literature. AB - Blunt cerebrovascular injuries (BCVI) have been a topic of interest to many researchers worldwide as evidenced by the vast amount of available literature. The interest in these rare injuries is probably due to the significant possibility of mortality and morbidity amongst patients who sustain them, when the employment of radiological screening methods could prevent such an outcome. Recognition of these injuries is the most important step towards prevention of adverse outcomes. We present a comprehensive review of the literature regarding the mechanism of injury, imaging, management, and complications of BCVI. Articles were identified through a search of MEDLINE and the Cochrane Central Register of Controlled Trials using the keywords Blunt; Vascular; Carotid; Vertebral; Trauma; Stroke; Management, and Endovascular. The search was limited to humans and articles in English. PMID- 22087393 TI - Umbilical Cord Blood Banking and Transplantation: A short review. AB - It is more than 20 years since the first cord blood transplant (CBT) was performed, following the realisation that cord blood (CB), which is normally wasted, is rich in progenitor cells and capable of rescuing haematopoiesis. Since then it has been appreciated that CB is rich in stem cells, and has many other features not the least of which is its ability to rescue the transplanted patient without a rigid need for full human lymphocyte antigen (HLA) compatibility. Also it is easily accessible, relatively free from infections and poses no medical risk to the donor. However, the quantity of the stem cells is rather small, thus predominantly restricting its use to children or adults requiring double units. In Oman, we have taken a keen interest in stem cell research and also CBT. We see such activities as an avenue for our patients, for whom a compatible bone marrow (BM) or a peripheral blood donor cannot be found, to have an alternative in the form of CBT. This has encouraged us to establish a national voluntary cord blood bank (CBB) which is a valuable option open to a selected group of patients, as compared to the controversial private CBB. This national CBB will have a better representation of HLA-types common in the region, an improvement on relying on banks in other countries. Considering the need for stem cell transplant/therapy in this country, it is only appropriate that this sort of bank is established to cater for some of these requirements. PMID- 22087394 TI - Neonatal Screening: Mean haemoglobin and red cell indices in cord blood from Omani neonates. AB - OBJECTIVES: The aim of this study was to validate the interpretation of red blood cell indices in complete blood count (CBC) and high performance liquid chromatography (HPLC) results on cord blood samples in consecutive Omani neonates. METHODS: Cord blood samples from 7,837 neonates, were analysed with CBC and HPLC using the beta-thalassaemia short programme. Direct sequencing of abnormal samples with HbS, HbD, HbE and HbC was performed to validate the HPLC results. Additionally, in cases with HbA beta10%, the beta-globin gene was directly sequenced for beta-thalassaemia mutation analysis. RESULTS: Overall, 4,042 subjects (51.58%) had normal HPLC (HbA 22.88+/-8.03; HbF 77.02+/-8.04), whereas the presence of Hb Barts in the remaining 3,795 cases (48.42%) indicated the presence of alpha-thalassaemia. No case of HbH was detected. In the former subgroup respectively, the mean Hb (15.38+/-2.04 g/dl) red blood cell (RBC) count (4.69+/-0.68 * 10(12)/l), Hct (50.5+/-7.18%), mean corpuscular volume (MCV) (107.66+/-7.75 fl), mean corpuscular haemoglobin (MCH) (33.31+/-4.07 pg), mean corpuscular haemoglobin concentration (MCHC) (30.98+/-3.44 g/dl), red cell distribution width (RDW) (17.01+/-2.17%) whereas, in the latter group with alpha thalassaemia, it was (14.79+/-2.90 g/dl); (5.09+/-0.77 * 10(12)/l); (49.7+/ 7.40%); (97.29+/-13.8 fl); (29.74+/-11.80 pg); (30.39+/-3.6 g/dl), and (18.09+/ 2.56%) respectively. DNA sequencing of samples with abnormal haemoglobin could validate the CBC and HLPC interpretations in all cases. CONCLUSION: This is the first study comparing the hemoglobin and red cell indices in the cord blood from newborn Omani subjects with those from other countries in the region, showing comparable results to those seen in Saudi neonates. The study also validates the CBC and HPLC interpretations of the cord blood red cell indices in the Omani neonate. The incidence of alpha-thalassaemia diagnosed by the presence of Hb Barts in cord blood of neonates was 48.42%. PMID- 22087395 TI - Simultaneous Detection of Dengue NS1 Antigen, IgM plus IgG and Platelet Enumeration during an Outbreak. AB - OBJECTIVES: During 2010, there was an increase in dengue virus infections in New Delhi, India compared to 2009. This study was conducted at Sant Parmanand Hospital during this outbreak to determine the utility of a 'Dengue Package', comprising simultaneous detection of dengue non-structural protein 1 (NS1), anti dengue IgM, anti-dengue IgG and platelet enumeration for early diagnosis, better case management and faster public health response. METHODS: Blood samples were tested for Dengue NS1, IgM and IgG using the single-step immunochromatigrahic One step dengue NS1 Ag and IgG/IgM test, while platelets were enumerated with automatic analysers yielding results within 1-2 hours. RESULTS: Of the 1,886 patients screened with the 'Dengue Package', 678 and 1208 were NS1-positive and negative respectively, in different combinations. In 394 cases, NS1 was exclusively positive while 29 were also IgG positive. In 942 cases NS1, IgM and IgG were negative (triple negative). The platelet counts in the NS1 positives were lower than the NS1 negatives, mean and standard deviation (SD) 116.8+/-70.2 * 10(9)/L: 95% confidence interval (CI) 66.6-74.1 and 167.2+/-94.0 * 10(9)/L, P<0.0001. Platelet counts were <20 * 10(9)/L in 20 NS1 antigen-positives and 42 NS1 antigen-negatives. CONCLUSION: During the 2010 outbreak, swift availability of the 'Dengue Package' assisted patient management, platelet transfusions, implementation of anti-vector measures and public health notifications. Testing for NS1 assisted the diagnosis of an additional 22.4% cases; of these 394 had evidence of primary infection and 29 of secondary infection. The 'Dengue Package' was useful in tackling the rise in suspected cases. PMID- 22087396 TI - Medical Tourism Abroad: A new challenge to Oman's health system - Al Dakhilya region experience. AB - OBJECTIVES: This study aimed to understand why people seek medical advice abroad given the trouble and expense this entails. The types of medical problems for which treatment abroad was sought, preferred destinations and satisfaction with the treatment were explored. A secondary aim was to give feedback to stakeholders in the health care system on how to handle this issue and meet the needs of the community. METHODS: 45 patients who had recently travelled abroad for treatment were asked to complete a questionnaire or were interviewed by telephone. RESULTS: 40 questionnaires were received. 68% of the respondents were male. Orthopaedic diseases were the most common conditions leading patients to seek treatment abroad. Thailand was the most popular destination followed by India (50% and 30% respectively). 85% of respondents went abroad for treatment only, 10% for treatment and tourism and 2.5% were healthy, but travelled abroad for a checkup. Interestingly, 15% of the participants went abroad without first seeking medical care locally. Out of those initially treated in Oman, 38.2% had no specific diagnosis and 38.2% had received treatment, but it was not effective. 73% of respondents obtained information on treatment abroad from a friend. The Internet and medical tourism offices were the least used sources of information. 15% of the patients experienced complications after their treatment abroad. CONCLUSION: Various facts about medical treatment abroad need to be disseminated to the public. This will necessitate greater effort in public health promotion and education. PMID- 22087397 TI - Prevalence and Impact of Dysmenorrhoea among Omani High School Students. AB - OBJECTIVES: The objectives of this study were to determine the prevalence of dysmenorrhoea in Omani high schoolgirls, its impact and the treatment used. METHODS: A cross-sectional survey was carried out in May 2010 on 404 girls from two public high schools in the Muscat region. Data were collected by self administered questionnaire including information on demographics, prevalence of dysmenorrhoea, severity, its impact, and the treatment used. RESULTS: Overall, 94% (n = 380) of the participants had dysmenorrhoea. It was mild in 27% (n = 104), moderate in 41% (n = 155), and severe in 32% (n = 121). Dysmenorrhoea was the cause of limited sports activities in 81%, decreased class concentration in 75%, restricted homework in 59%, school absenteeism in 45%, limited social activities in 25%, and decreased academic performance in 8% of the affected students. Only 3% (n = 10) had consulted a physician; 21% (n = 80) self medicated, and 55% (n = 210) took no action. The commonest drugs used were paracetamol (n = 60, 16%), ibuprofen (n = 29, 8%) and mefenemic acid (n = 12, 3%). There was no statistically significant correlation between dysmenorrhoea, demographics and menstrual characteristics. CONCLUSION: Dysmenorrhoea is a prevalent and yet undertreated menstrual disorder among Omani adolescent schoolgirls. The pain suffered can be severe and disabling. Doctors should therefore be prepared to discuss this more freely with schoolgirls. In addition, there is a need for education regarding dysmenorrhoea and treatment options to minimise the impact on school, sports, social and daily activities. PMID- 22087398 TI - Information mastery, effective health care, evidence-based practice and the otolaryngologist. AB - OBJECTIVES: The objectives of this study were to study the information-seeking behaviour of otolaryngologists in Oman, and their willingness to learn and acquire evidence-based practice (EBP) skills. METHODS: A cross-sectional survey was carried out by distribution of a questionnaire to 63 otolaryngologists (ranging from residents to consultants) employed in Oman who attended a national otolaryngology meeting in January 2010. RESULTS: Forty-nine completed questionnaires were received; 57% of the respondents had more than 10 years' experience, and 60% were from tertiary care; 38.8% "totally agreed", and 36.7% "partially agreed" that EBP would improve the quality of care and thus provide effective health care to patients. More than 46.9% had 1-5 questions per week, 18.4% had 11 or more questions per week at the point-of-care; 69.4% were willing to acquire information mastery skills. There was a statistical correlation between the number of years of experience, the number of questions, and willingness to acquire information mastery skills. CONCLUSION: In day-to-day clinical practice, web-based resources are of increasing significance. Most otolaryngologists in Oman not only believed that it is essential to acquire information mastery skills, but also that effective health care depends on such skills and on EBP. Most were willing to acquire these skills. In the future, these skills will be vital in helping otolaryngologists deliver effective health care solutions. PMID- 22087399 TI - Laparoscopic surgery recording as an adjunct to conventional modalities of teaching gross anatomy. AB - OBJECTIVES: In order to increase their effectiveness, methods of teaching morphological sciences need to be revised to incorporate the recent technological advances made in the field of medicine. Teaching human structure with conventional methods of prosections using dissected cadaveric specimen alone quite often fails to prepare students adequately for their clinical training. A learner-oriented method, incorporating three dimensional spatial anatomy and more closely mirroring the clinical setting, is required. METHODS: With these challenges in mind, a 30-minute slow-paced video recording of a cholecystectomy performed laproscopically on a 45 year-old lady was adapted to supplement the conventional teaching of anatomy of the abdomen and pelvis. This study was carried out in October 2010. RESULTS: The subjects of this study were 84 students in a first year preclinical MD course in human structure at the private Oman Medical College. Their feedback was obtained via questionnaire and revealed that the video presentation helped the students to realise the significance of the anatomical details learnt during the human structure course. CONCLUSION: Recordings of laparoscopic surgeries are an effective preclinical anatomy teaching resource in student-centred learning. They also help the students to appreciate the clinical relevance of gross anatomy and enhance their motivation to learn. PMID- 22087400 TI - Nephropathic Cystinosis: First reported case in Oman. AB - Cystinosis is an autosomal recessive, lysosomal storage disease characterised by the accumulation of the amino acid cystine in different organs and tissues. It is a multisystemic disease that can present with renal and extra renal manifestations. There are three types of cystinosis, infantile nephropathic cystinosis being the most severe form. In this report we present the classic clinical features of nephropathic cystinosis in an Omani child. This condition remains quite rare in the Middle East and is the first reported case of nephropathic cystinosis in the Omani population. PMID- 22087401 TI - Atypical case of acute Fatty liver of pregnancy. AB - Acute fatty liver of pregnancy (AFLP) is a life threatening obstetric emergency. The most common presentation is malaise, nausea, vomiting and epigastric pain followed by jaundice. Due to high maternal and perinatal mortality, early diagnosis, prompt delivery and supportive care are required. We report an atypical case of AFLP and discuss the management and complications of this rare obstetric disorder. PMID- 22087402 TI - Cannabis Exposure in an Omani Child: First case report from Oman. AB - We report a confirmed case of cannabis exposure in an Omani female child with developmental delay. Cannabis exposure in children can lead to many consequences; for example, chronic use can result in developmental delay, abnormal behaviour, and hyperactivity while there is a risk of coma with acute exposure. It is important for clinicians to consider substance abuse as a differential diagnosis for similar presentations in paediatric patients, noting that children are at risk of cannabis exposure if their parents/caregivers are cannabis users. PMID- 22087403 TI - Laparoscopic repair of traumatic intraperitoneal bladder rupture. AB - Intraperitoneal rupture of the bladder is an uncommon condition that is usually caused by pelvic fractures. This is a true surgical emergency managed conventionally by open laparotomy with single or double layer repair. We present a case of successful laparoscopic repair of an intraperitoneal bladder rupture secondary to blunt abdominal trauma and pelvic fracture in a 37 year-old man. The repair was done using single layer repair, with successful results. PMID- 22087404 TI - Complications of Central Venous Catheterisation: Breakage of guidewire-a disaster averted. AB - Central venous catheterisation (CVC) is a common bedside invasive procedure done in medical practice. Even though it is a safe procedure when done with ultrasound guidance, difficulties and complications do occur even in experienced hands. Here, we describe the difficulties encountered in the form of the breakage of the guidewire while inserting a CVC in a patient with sickle cell disease. PMID- 22087405 TI - Newly diagnosed acute myeloid leukemia with neck swelling. PMID- 22087406 TI - Is it not the time to stop the use of Scoline (suxamethonium chloride) for rapid sequence intubation? PMID- 22087407 TI - GlideScope for Assessment of Recurrent Laryngeal Nerve Integrity after Thyroid Surgery. PMID- 22087408 TI - Re: Hepatitis B Vaccine Coverage and the Immune Response in Children under ten years old in Sana'a, Yemen-We need to work much harder to control hepatitis B virus infection in developing countries. PMID- 22087409 TI - Re: dengue haemorrhagic Fever presenting as acute abdomen. PMID- 22087410 TI - In memory of Ralph Steinman. PMID- 22087411 TI - A short-term clinical study of marginal bone level change around microthreaded and platform-switched implants. AB - PURPOSE: The marginal bone levels around implants following restoration are used as a reference for evaluating implant success and survival. Two design concepts that can reduce crestal bone resorption are the microthread and platform switching concepts. The aims of this study were to analyze the placement of microthreaded and platform-switched implants and their short-term survival rate, as well as the level of bone around the implants. METHODS: The subjects of this study were 27 patients (79 implants) undergoing treatment with microthreaded and platform-switched implants between October 2008 and July 2009 in the Dental Hospital of Yonsei University Department of Periodontology. The patients received follow-up care more than 6 months after the final setting of the prosthesis, at which time periapical radiographs were taken. The marginal bone level was measured from the reference point to the lowest observed point of contact between the marginal bone and the fixture. Comparisons were made between radiographs taken at the time of fixture installation and those taken at the follow-up visit. RESULTS: During the study period (average of 11.8 months after fixture installation and 7.4 months after the prosthesis delivery), the short-term survival rate of microthreaded and platform-switched implants was 100% and the marginal bone loss around implants was 0.16+/-0.08 mm, the latter of which is lower than the previously reported values. CONCLUSIONS: This short-term clinical study has demonstrated the successful survival rates of a microthread and platform-switched implant system, and that this system is associated with reduced marginal bone loss. PMID- 22087412 TI - The evaluation of the correlation between histomorphometric analysis and micro computed tomography analysis in AdBMP-2 induced bone regeneration in rat calvarial defects. AB - PURPOSE: Micro-computed tomography (micro-CT) has been widely used in the evaluation of regenerated bone tissue but the reliability of micro-CT has not yet been established. This study evaluated the correlation between histomorphometric analysis and micro-CT analysis in performing new bone formation measurement. METHODS: Critical-size calvarial defects were created using a 8 mm trephine bur in a total of 24 Sprague-Dawley rats, and collagen gel mixed with autogenous rat bone marrow stromal cells (BMSCs) or autogenous rat BMSCs transduced by adenovirus containing bone morphogenic protein-2 (BMP-2) genes was loaded into the defect site. In the control group, collagen gel alone was loaded into the defect. After 2 and 4 weeks, the animals were euthanized and calvaria containing defects were harvested. Micro-CT analysis and histomorphometric analysis of each sample were accomplished and the statistical evaluation about the correlation between both analyses was performed. RESULTS: New bone formation of the BMP-2 group was greater than that of the other groups at 2 and 4 weeks in both histomorphometric analysis and micro-CT analysis (P=0.026, P=0.034). Histomorphometric analysis of representative sections showed similar results to histomorphometric analysis with a mean value of 3 sections. Measurement of new bone formation was highly correlated between histomorphometric analysis and micro CT analysis, especially at the low lower threshold level at 2 weeks (adjusted r(2)=0.907, P<0.001). New bone formation of the BMP-2 group analyzed by micro-CT tended to decline sharply with an increasing lower threshold level, and it was statistically significant (P<0.001). CONCLUSIONS: Both histomorphometric analysis and micro-CT analysis were valid methods for measurement of the new bone in rat calvarial defects and the ability to detect the new bone in micro-CT analysis was highly influenced by the threshold level in the BMP-2 group at early stage. PMID- 22087413 TI - Response of osteoblast-like cells cultured on zirconia to bone morphogenetic protein-2. AB - PURPOSE: The aim of this study was to compare osteoblast behavior on zirconia and titanium under conditions cultured with bone morphogenetic protein-2. METHODS: MC3T3-E1 cells were cultured on sandblasted zirconia and sandblasted/etched titanium discs. At 24 hours after seeding MC3T3-E1, the demineralized bone matrix (DBM) gel alone and the DBM gel with bone morphogenetic protein-2 (BMP-2) were added to the culture medium. The surface topography was examined by confocal laser scanning microscopy. Cellular proliferation was measured at 1, 4, and 7 days after gel loading. Alkaline phosphatase activity was measured at 7 days after gel loading. The mRNA expression of ALPase, bone sialoprotein, type I collagen, runt-related transcription factor 2 (Runx-2), osteocalcin, and osterix were evaluated by real-time polymerase chain reaction at 4 days and 7 days. RESULTS: At 1, 4, and 7 days after loading the DBM gel alone and the DBM gel with BMP-2, cellular proliferation on the zirconia and titanium discs was similar and that of the groups cultured with the DBM gel alone and the DBM gel with BMP-2 was not significantly different, except for titanium with BMP-2 gel. ALPase activity was higher in the cells cultured with BMP-2 than in the other groups, but there was no difference between the zirconia and titanium. In ALPase, bone sialoprotein, osteocalcin, Runx-2 and osterix gene expression, that of cells on zirconia or titanium with BMP-2 gel was much more highly increased than titanium without gel at day 7. The gene expression level of cells cultured on zirconia with BMP-2 was higher than that on titanium with BMP-2 at day 7. CONCLUSIONS: The data in this study demonstrate that the osteoblastic cell attachment and proliferation of zirconia were comparable to those of titanium. With the stimulation of BMP-2, zirconia has a more pronounced effect on the proliferation and differentiation of the osteoblastic cells compared with titanium. PMID- 22087414 TI - The effect of erbium-doped: yttrium, aluminium and garnet laser irradiation on the surface microstructure and roughness of double acid-etched implants. AB - PURPOSE: One of the most frequent complications related to dental implants is peri-implantitis, and the characteristics of implant surfaces are closely related to the progression and resolution of inflammation. Therefore, a technical modality that can effectively detoxify the implant surface without modification to the surface is needed. The purpose of this study was to evaluate the effect of erbium-doped: yttrium, aluminium and garnet (Er:YAG) laser irradiation on the microstructural changes in double acid-etched implant surfaces according to the laser energy and the application duration. METHODS: The implant surface was irradiated using an Er:YAG laser with different application energy levels (100 mJ/pulse, 140 mJ/pulse, and 180 mJ/pulse) and time periods (1 minute, 1.5 minutes, and 2 minutes). We then examined the change in surface roughness value and microstructure. RESULTS: In a scanning electron microscopy evaluation, the double acid-etched implant surface was not altered by Er:YAG laser irradiation under the condition of 100 mJ/pulse at 10 Hz for any of the irradiation times. However, we investigated the reduced sharpness of the specific ridge microstructure that resulted under the 140 mJ/pulse and 180 mJ/pulse conditions. The reduction in sharpness became more severe as laser energy and application duration increased. In the roughness measurement, the double acid-etched implants showed a low roughness value on the valley area before the laser irradiation. Under all experimental conditions, Er:YAG laser irradiation led to a minor decrease in surface roughness, which was not statistically significant. CONCLUSIONS: The recommended application settings for Er:YAG laser irradiation on double acid-etched implant surface is less than a 100 mJ/pulse at 10 Hz, and for less than two minutes in order to detoxify the implant surface without causing surface modification. PMID- 22087415 TI - The effect of fibronectin-coated implant on canine osseointegration. AB - PURPOSE: The purpose of this study was to characterize the osseointegration of the fibronectin-coated implant surface. METHODS: Sand-blasted, large-grit, acid etched (SLA) surface implants, with or without a thin calcium phosphate and fibronectin coating, were placed in edentulous mandibles of dogs 8 weeks after extraction. All dogs were sacrificed forhistological and histomorphometric evaluation after 4- and 8-week healing periods. RESULTS: All types of implants were clinically stable without any mobility. Although the bone-to-implant contact and bone density of the SLA implants coated with calcium phosphate (CaP)/fibronectin were lower than the uncoated SLA implants, there were no significant differences between the uncoated SLA surface group and the SLA surface coated with CaP/fibronectin group. CONCLUSIONS: Within the limits of this study, SLA surfaces coated with CaP/fibronectin were shown to have comparable bone-to-implant contact and bone density to uncoated SLA surfaces. PMID- 22087416 TI - The use of definitive implant abutments for the fabrication of provisional crowns: a case series. AB - PURPOSE: The anterior region is a challenge for most clinicians to achieve optimal esthetics with dental implants. The provisional crown is a key factor in the success of obtaining pink esthetics around restorations with single implants, by soft tissue and inter-proximal papilla shaping. Provisional abutments bring additional costs and make the treatment more expensive. Since one of the aims of the clinician is to reduce costs and find more economic ways to raise patient satisfaction, this paper describes a practical method for chair-side fabrication of non-occlusal loaded provisional crowns used by the authors for several years successfully. METHODS: Twenty two patients (9 males, 13 females; mean age, 36,72 years) with one missing anterior tooth were treated by using the presented method. Metal definitive abutments instead of provisional abutments were used and provisional crowns were fabricated on the definitive abutments for all of the patients. The marginal fit was finished on a laboratory analogue and temporarily cemented to the abutments. The marginal adaptation of the crowns was evaluated radiographically. RESULTS: The patients were all satisfied with the final appearance and no complications occurred until the implants were loaded with permanent restorations. CONCLUSIONS: The use of the definitive abutments for provisional crowns instead of provisional abutments reduces the costs and the same results can be obtained. PMID- 22087417 TI - Secondary closure of an extraction socket using the double-membrane guided bone regeneration technique with immediate implant placement. AB - PURPOSE: Immediate implantation presents challenges regarding site healing, osseointegration, and obtaining complete soft-tissue coverage of the extraction socket, especially in the posterior area. This last issue is addressed herein using the double-membrane (collagen membrane+high-density polytetrafluoroethylene [dPTFE] membrane) technique in two clinical cases of posterior immediate implant placement. METHODS: An implant was placed immediately after atraumatically extracting the maxillary posterior tooth. The gap between the coronal portion of the fixture and the adjacent bony walls was filled with allograft material. In addition, a collagen membrane (lower) and dPTFE membrane (upper) were placed in a layer-by-layer manner to enable the closure of the extraction socket without a primary flap closure, thus facilitating the preservation of keratinized mucosa. The upper dPTFE membrane was left exposed for 4 weeks, after which the membrane was gently removed using forceps without flap elevation. RESULTS: There was considerable plaque deposition on the outer surface of the dPTFE membrane but not on the inner surface. Moreover, scanning electron microscopy of the removed membrane revealed only a small amount of bacteria on the inner surface of the membrane. The peri-implant tissue was favorable both clinically and radiographically after a conventional dental-implant healing period. CONCLUSIONS: Secondary closure of the extraction socket and immediate guided bone regeneration using the double-membrane technique may produce a good clinical outcome after immediate placement of a dental implant in the posterior area. PMID- 22087418 TI - The evolution of urogenital tissue engineering. PMID- 22087420 TI - Dissimilar effects of tolterodine on detrusor overactivity in awake rats with chemical cystitis and partial bladder outlet obstruction. AB - PURPOSE: We investigated bladder function, with a special focus on nonvoiding contractions (NVCs), in awake rats with chronic chemical cystitis and bladder outlet obstruction (BOO) by use of simultaneous registrations of intravesical and intraabdominal pressures. In addition, we tested the effects of tolterodine on the NVCs in these models. METHODS: A total of 20 female Sprague-Dawley rats were used in this study. In eight rats, chemical cystitis was induced by intravesical instillation of HCl. Twelve rats were subjected to sham instillations or partial BOO. Four weeks after intravesical instillation or 2 weeks after partial BOO, cystometrograms were obtained by use of simultaneous recording of intravesical and intraabdominal pressure in all unanesthetized, unrestrained rats in metabolic cages. RESULTS: A total of 17 rats survived. In the rats with acute injury by HCl, 50% showed detrusor overactivity (DO), which was not seen in the sham group. The cystitis group had lower DO pressure without a difference in DO frequency compared with the BOO group. After the administration of tolterodine, the cystitis group showed no difference in DO frequency or pressure, whereas the BOO group showed decreased values for both parameters. CONCLUSIONS: Our study showed that toleterodine produced no effect on DO during the filling phase in rats with chronic chemical cystitisbut decreased the frequency and pressure of DO in rats with BOO. Clinically, studies are needed to improve the treatment effect of anticholinergic drugs ininterstitial cystitis patients with overactive bladder. PMID- 22087421 TI - Exploring the potential of flunarizine for Cisplatin-induced painful uremic neuropathy in rats. AB - PURPOSE: The present study was designed to explore the potential of flunarizine for cisplatin induced painful uremic neuropathy in rats. METHODS: Cisplatin (2 mg/kg; i.p., for 5 consecutive days) was administered and renal uremic markers i.e., serum creatinine were estimated on days 4 and 25. Behavioral changes were assessed in terms of thermal hyperalgesia (hot plate, plantar, tail immersion, and tail flick tests at different time intervals). Biochemical analysis of total calcium, superoxide anion, DNA, and transketolase, and myeloperoxidase activity in tissue samples was also performed. Furthermore, flunarizine (100, 200, and 300 uM/kg; p.o., for 21 consecutive days) was administered to evaluate its potency on uremic neuropathy, and the results were compared with those for the carbamazepine treated (30 mg/kg; p.o., for 21 consecutive days) groups. RESULTS: Flunarizine attenuated the cisplatin-induced uremic neuropathy, and the degree of behavioral and biochemical changes in serum and tissue samples in a dose dependent manner. The medium and high doses of flunarizine were shown to produce a significant effect on cisplatin induced painful uremic neuropathy. CONCLUSIONS: Our results indicate the potential of flunarizine for anti-oxidative, anti-inflammatory, and neuroprotective actions. Therefore, it may have use as a novel therapeutic agent for the management of painful uremic neuropathy. PMID- 22087419 TI - Regenerative medicine strategies for treating neurogenic bladder. AB - Neurogenic bladder is a general term encompassing various neurologic dysfunctions of the bladder and the external urethral sphincter. These can be caused by damage or disease. Therapeutic management options can be conservative, minimally invasive, or surgical. The current standard for surgical management is bladder augmentation using intestinal segments. However, because intestinal tissue possesses different functional characteristics than bladder tissue, numerous complications can ensue, including excess mucus production, urinary stone formation, and malignancy. As a result, investigators have sought after alternative solutions. Tissue engineering is a scientific field that uses combinations of cells and biomaterials to encourage regeneration of new, healthy tissue and offers an alternative approach for the replacement of lost or deficient organs, including the bladder. Promising results using tissue engineered bladder have already been obtained in children with neurogenic bladder caused by myelomeningocele. Human clinical trials, governed by the Food and Drug Administration, are ongoing in the United States in both children and adults to further evaluate the safety and efficacy of this technology. This review will introduce the principles of tissue engineering and discuss how it can be used to treat refractory cases of neurogenic bladder. PMID- 22087422 TI - Korean version of the overactive bladder symptom score questionnaire: translation and linguistic validation. AB - PURPOSE: The overactive bladder symptom score (OABSS) consists of 4 questions regarding OAB symptoms. The aim of this study was to develop Korean version of the OABSS from the original Japanese version, with subsequent linguistic validation. METHODS: Between February and May 2008, the translation and linguistic validation process was performed as follows: a forward translation, reconciliation, backward translation, cognitive debriefing, and final proofreading. RESULTS: A forward translation from the original version of the OABSS to the Korean language was carried out by 2 native Korean speakers, who were also fluent in Japanese. Reconciliation was made after review of both translations by a panel consisting of both translators and one of the authors. Another bilingual translator who had never seen the original version of the OABSS carried out a translation of the reconciled version back into Japanese, and the original and backward-translated versions were subsequently compared. After discussion of all discrepancies between both versions by the panel, a second Korean version was produced. During cognitive debriefing, 5 outpatients with OAB reported that each question of the Korean version was significant and appropriate for their symptoms. However, 2 patients said that some parts of the questions or instructions were not clear or were not easy to understand. According to the cognitive debriefing, some words and phrases were revised into more understandable expressions. CONCLUSIONS: A Korean version of the OABSS was developed and linguistic validation was performed. Further studies are needed to assess the reproducibility and validity of the questionnaire in Korean populations. PMID- 22087423 TI - The impact of overactive bladder on health-related quality of life, sexual life and psychological health in Korea. AB - PURPOSE: We aimed to estimate the prevalence of overactive bladder (OAB) in Korea, to assess the variation in prevalence by sex and age, and to measure the impact of OAB on quality of life. METHODS: A population-based, cross-sectional telephone survey was conducted between April and June 2010 with a questionnaire regarding the prevalence of OAB, demographics, and the impact of OAB on quality of life. A geographically stratified random sample of men and women aged >=30 years was selected. RESULTS: The overall prevalence of OAB was 22.9% (male, 19%; female, 26.8%). Of a total of 458 participants with OAB, 37.6% and 19.9% reported moderate or severe impact on their daily life and sexual life (5.6% and 3.5%, respectively, in participants without OAB). Anxiety and depression were reported by 22.7% and 39.3% of participants with OAB, respectively (9.7% and 22.8%, respectively, in participants without OAB). Only 19.7% of participants with OAB had consulted a doctor for their voiding symptoms, but 50.7% of respondents with OAB were willing to visit a hospital for the management of their OAB symptoms. CONCLUSIONS: This study confirmed that OAB symptoms are highly prevalent in Korea, and many sufferers appear to have actively sought medical help. OAB has severe effects on daily and sexual life as well as psychological health. PMID- 22087424 TI - Effect of 5-alpha Reductase Inhibitor on Storage Symptoms in Patients with Benign Prostatic Hyperplasia. AB - PURPOSE: Many patients with benign prostatic hyperplasia (BPH) have storage symptoms. The aim of this study was to evaluate the effects of treatment with a 5 alpha reductase inhibitor (5ARI) on storage symptoms in patients with BPH. METHODS: This study was conducted in 738 patients with lower urinary tract symptoms secondary to BPH. Patients with a prostate volume of higher than 30 mL on the transrectal ultrasound were classified into two groups: group A, in which an alpha blocker was solely administered for at least 12 months, and group B, in which a combination treatment regimen of an alpha blocker plus 5ARI was used. This was followed by an analysis of the changes in parameters such as the total International Prostate Symptom Score (IPSS), voiding symptom subscore, and storage symptom subscore between the two groups. In addition, we examined whether there was a significant difference between the two groups in the degree of change in storage symptoms between before and after the pharmacological treatment. RESULTS: Of the 738 men, 331 had a prostate volume >=30 mL, including 150 patients in group A and 181 patients in group B. Total IPSS, the voiding symptom subscore, and the storage symptom subscore were significantly lower after treatment than before treatment in both groups (P<0.05). A comparison of the degree of change between before and after treatment, however, showed no significant differences in the storage symptom subscore between the two groups (P>0.05). CONCLUSIONS: Alpha blocker and 5ARI combination treatment is effective for patients with BPH including storage symptoms. However, 5ARI does not exert a significant effect on storage symptoms in BPH patients. PMID- 22087425 TI - Predictors of Successful Trial without Catheter for Postoperative Urinary Retention Following Non-Urological Surgery. AB - PURPOSE: To investigate the success rate of trial without catheter (TWOC) for postoperative urinary retention (POUR) after non-urological surgery and to determine predictors of successful TWOC. METHODS: A total of 104 patients who underwent non-urological surgery and were referred to the department of urology for POUR were included in this retrospective study. All eligible patients underwent indwelling catheterization as an initial treatment and then TWOC was performed 3 to 7 days later. POUR was defined as micturition difficulty with greater than 400 mL of postvoid residual (PVR) urine volume measured by catheterization after non-urological surgery. Successful TWOC was defined as voiding with less than 100 mL of PVR urine volume. Predictive factors were identified by multivariate regression analysis. All definitions corresponded to recommendations of the International Continence Society. RESULTS: The mean age of the patients was 65.2 (range, 23 to 92) years. There were 45 male and 59 female patients. Intraoperative indwelling catheterization was performed in 69 (66.3%) patients. Mean duration of indwelling catheterization for POUR was 5.0 (range, 3.0 to 7.0) days and 83 (79.8%) patients received medication with an alpha blocker. A successful TWOC was observed in 70 (67.4%) patients. The mean age of the patients with failure of TWOC was significantly higher than that of the patients with successful TWOC. The percentages of female patients, spinal surgery, and prone position during surgery in patients with unsuccessful TWOC were higher than in those with successful TWOC. In the multivariate logistic regression analysis, age and location of surgery (spine vs. non-spine) were the independent predictors of successful TWOC for POUR. CONCLUSIONS: Our data suggest that older age and spinal surgery may be important risk factors for failure of TWOC for POUR after non-urological surgery. Thus, adequate prevention measures may be necessary for POUR after non-urological surgery, especially in patients with these risk factors. PMID- 22087426 TI - Voiding dysfunction after total mesorectal excision in rectal cancer. AB - PURPOSE: The aim of this study was to assess the voiding dysfunction after rectal cancer surgery with total mesorectal excision (TME). METHODS: This was part of a prospective study done in the rectal cancer patients who underwent surgery with TME between November 2006 and June 2008. Consecutive uroflowmetry, post-voided residual volume, and a voiding questionnaire were performed at preoperatively and postoperatively. RESULTS: A total of 50 patients were recruited in this study, including 28 male and 22 female. In the comparison of the preoperative data with the postoperative 3-month data, a significant decrease in mean maximal flow rate, voided volume, and post-voided residual volume were found. In the comparison with the postoperative 6-month data, however only the maximal flow rate was decreased with statistical significance (P=0.02). In the comparison between surgical methods, abdominoperineal resection patients showed delayed recovery of maximal flow rate, voided volume, and post-voided residual volume. There was no significant difference in uroflowmetry parameters with advances in rectal cancer stage. CONCLUSIONS: Voiding dysfunction is common after rectal cancer surgery but can be recovered in 6 months after surgery or earlier. Abdominoperineal resection was shown to be an unfavorable factor for postoperative voiding. Larger prospective study is needed to determine the long-term effect of rectal cancer surgery in relation to male and female baseline voiding condition. PMID- 22087427 TI - Efficacy of anticholinergics for chronic prostatitis/chronic pelvic pain syndrome in young and middle-aged patients: a single-blinded, prospective, multi-center study. AB - PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) exhibits variable lower urinary tract symptoms (LUTS). The aim of this study was to evaluate the incidence of LUTS and the efficacy of an anticholinergic agent in young and middle-aged CP/CPPS patients. METHODS: Ninety-six men with CP/CPPS were randomly assigned in a single-blind fashion and received either ciprofloxacin (group 1, 49 patients) or ciprofloxacin and solifenacin (5 mg/day; group 2, 47 patients) for 8 weeks. The National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), the International Prostate Symptom Score (IPSS), and the International Index of Erectile Function-5 (IIEF-5) were used to grade the patients' symptoms and the quality of life impact at the start of the study, and at 4 and 8 weeks from the initiation of the study. RESULTS: There was no significant difference between groups 1 and 2 with respect to age, duration of disease, or sub-domains of the IPSS, NIH-CPSI, or IIEF-5 at baseline. Of these patients, 67.4% had LUTS. Statistically significant differences were determined via the NIH-CPSI for total score and the pain and urinary domain scores. Statistically significant differences were determined via the IPSS for total score and the storage domain score. The total score of the IIEF-5 increased, but the change was not significant. There was no statistically significant difference in residual urine. CONCLUSIONS: Many CP/CPPS patients had LUTS. Solifenacin in CP/CPPS demonstrated improvements in the NIH-CPSI and the IPSS total score and storage score. Storage factors significantly improved via the NIH-CPSI and IPSS assessments in the solifenacin treatment group. PMID- 22087428 TI - Atrophy of the tongue as the presenting feature of metastatic prostate cancer. AB - Prostate cancer is the most frequently diagnosed solid organ cancer in men and is the second leading cause of cancer-related deaths in men in the United Kingdom. Commonly, it metastasizes to bones and lymph nodes, however, in advanced hormonerefractory disease it may involve the skull base leading to associated cranial nerve palsies. Cranial nerve palsy as the presenting feature of advanced hormone-sensitive prostate cancer is extremely rare. To the best of our knowledge, we report the first case of solitary hypoglossal nerve palsy as the presenting feature of advanced prostate cancer. Neurologists, neurosurgeons and otolaryngologists may be the first clinicians to see such a patient; therefore, prostate cancer should be amongst the differential diagnoses considered in middle aged and elderly men presenting with a cranial neuropathy and evidence of skull metastasis. PMID- 22087429 TI - Erratum: urodynamic findings in an awake chemical cystitis rat model observed by simultaneous registrations of intravesical and intraabdominal pressures. AB - [This corrects the article on p. 54 in vol. 14, PMID: 21120177.]. PMID- 22087430 TI - Erratum: Tape Shortening for Recurrent Stress Urinary Incontinence After Transobturator Tape Sling: 3-Year Follow-up Results. AB - [This corrects the article on p. 164 in vol. 14, PMID: 21179334.]. PMID- 22087431 TI - Pathogenesis of Interstitial Lung Disease in Children and Adults. AB - Interstitial lung diseases (ILDs) occur across the lifespan, from birth to advanced age. However, the causes, clinical manifestations, histopathology, and management of ILD differ greatly among infants, older children, and adults. The historical approach of classifying childhood ILD (chILD) using adult classification schemes may therefore have done more harm than good. Nevertheless, identification of novel forms of chILD in the past decade, such as surfactant metabolism dysfunction disorders and neuroendocrine cell hyperplasia of infancy (NEHI), as well as genomic analysis of adult ILDs, has taught us that identical genotypes may result in distinct phenotypes at different ages and developmental stages, and that lung developmental pathways and cellular phenotypes are often recapitulated in adult ILDs. Thus comparison of the pathophysiology of ILD in children and adults in the context of lung development is useful in understanding the pathogenesis of these disorders, and may lead to novel therapeutic interventions for ILDs at all ages. PMID- 22087433 TI - Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata. AB - An ever increasing demand for new lead compounds in the pharmaceutical industry has led scientists to search for natural bioactive products. Based on this extensive research, marine invertebrates now represent a rich source of novel substances with significant anti-neoplastic activities. As the current approach of synthesizing new and chemically modifying old drugs seems to have slowed down, and the identification of new anticancer drugs is not too promising, a new approach is clearly needed. The objective of this review is to present up-to-date data on these newer compounds. Based on the data summarized in this short review, it is clear that marine invertebrates represent an extremely important source of compounds with potential anti-cancer effects. Considering that we tested only a tiny number of Porifera and Coelenterata, the best is yet to come. PMID- 22087432 TI - Genetic Basis of Children's Interstitial Lung Disease. AB - Specific genetic causes for children's interstitial lung disease (chILD) have been identified within the past decade. These include deletions of or mutations in genes encoding proteins important in surfactant production and function (SP-B, SP-C, and ABCA3), surfactant catabolism (GM-CSF receptor), as well as transcription factors important for surfactant production (TTF1) or lung development (Fox F1), with heterozygous deletions or loss-of-function mutations of the latter resulting in alveolar capillary dysplasia (ACD) with misalignment of the pulmonary veins. Familial pulmonary fibrosis in adults may result from mutations in genes encoding components of telomerase and SP-A2. While not yet reported in children, the expression of these genes in alveolar type II epithelial cells supports a key role for the disruption of normal homeostasis in this cell type in the pathogenesis of interstitial lung disease. The identification of specific genetic causes for chILD now allows for the possibility of non-invasive diagnosis, and provides insight into basic cellular mechanisms that may allow the development of novel therapies. PMID- 22087434 TI - Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Bryozoa, Mollusca, Echinodermata and Urochordata. AB - The marine environment provides a rich source of natural products with potential therapeutic application. This has resulted in an increased rate of pharmaceutical agents being discovered in marine animals, particularly invertebrates. Our objective is to summarize the most promising compounds which have the best potential and may lead to use in clinical practice, show their biological activities and highlight the compounds currently being tested in clinical trials. In this paper, we focused on Bryozoa, Mollusca, Echinodermata and Urochordata. PMID- 22087436 TI - First Medical Olympiad. PMID- 22087435 TI - Epidermal growth factor receptor and K-Ras in non-small cell lung cancer molecular pathways involved and targeted therapies. AB - Lung cancer is currently the leading cause of cancer death in Western nations. Non-small cell lung cancer (NSCLC) represents 80% of all lung cancers, and adenocarcinoma is the predominant histological type. Despite the intensive research carried out on this field and therapeutic advances, the overall prognosis of these patients remains unsatisfactory, with a 5-year overall survival rate of less than 15%. Nowadays, pharmacogenetics and pharmacogenomics represent the key to successful treatment. Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma: one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor (EGFR). The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR (erlotinib and gefitinib) and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs. This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR, K-Ras and EGFR targeted therapies in NSCLC tumor behavior. PMID- 22087437 TI - Currently applied cross-sectional diagnostic modalities and imaging guided interventional modalities for treatment of neuroendocrine tumors. AB - Technological advances in conventional cross-sectional diagnostic imaging have allowed important modalities like ultrasonography, endoscopic ultrasonography, multi-detector computed tomography, nuclear medicine single photon emission tomography, positron emission tomography and magnetic resonance imaging to exhibit an increasingly important role in the diagnosis and management of patients with neuroendocrine tumors (NET). The arterial supply of metastatic lesions provides promising treatment options through the arterial route, hence transcatheter arterial embolization has a key role in the therapeutic management of metastatic NET. The various transcatheter methods of NET treatment are discussed, including radio-embolization. Imaging-guided percutaneous interventional radiologic methods of ablation are also discussed as applicable for the effective management of primary and metastatic NET. An approach to represent the physical and technical principles on which ablative methods rely and their clinical significance has been attempted. PMID- 22087438 TI - Reduced grey matter metabolism due to white matter edema allows optimal assessment of brain tumors on 18F-FDG-PET. AB - The main aim of this research was to demonstrate that the cortical and subcortical grey matter hypometabolism as revealed by fluorine-18 fluorodesoxyglucose-positron emission tomography ((18)F-FDG-PET) imaging in brain tumors is related to associated edema as demonstrated by magnetic resonance imaging (MRI). This in turn enhances the ability to assess disease activity in the tumor and the degree of loss of cerebral function in the adjacent and distant structures. We evaluated brain T1 and T2 weighted MRI and (18)F-FDG-PET scans of 29 patients (19 adult, 10 pediatric) with history of brain tumor. Tumor histology types included 21 gliomas, 1 melanoma, 1 primitive neuroectodermal tumor, 3 medulloblastomas and 3 ependymomas. The majority of scans were performed within the same week (94% <1 month. The extent of hypo and hypermetabolism was assessed on the (18)F-FDG-PET scans. A template of 12 regions of interest (ROI) was applied and the laterality indices of the regional counts (signal intensity) were computed. Extent of edema, enhancement, and anatomical change were assessed on the MRI scans. Extent of edema in the same ROI was evaluated by a 6-point semiquantitative scale and laterality indices were generated. Metabolic activity of the grey matter was correlated with the extent of edema using these indices. In all cases where edema was present, significant hypometabolism was observed in the adjacent structures. Overall, there was a strong correlation between the extent of edema and severity of hypometabolism (r=0.92, P=0.01). This was true regardless of the location of edema, whether there was history of radiation treatment (r=0.91, P=0.03), or not (r=0.97, P=0.17). In conclusion, edema independent of underlying variables appeared to contribute significantly to cortical and sub-cortical grey matter hypometabolism observed in patients with brain tumors. This would indicate that brain tumors can be successfully assessed by (18)F-FDG-PET and therefore the efforts for utilizing other tracers may not be justified. PMID- 22087439 TI - Differentiation of histological subtypes in lung cancer with 18F-FDG-PET 3-point imaging and kinetic analysis. AB - The purpose of this study was to evaluate differences in histological subtypes of lung cancer using (18)F-FDG-PET 3-point imaging and kinetic analysis. Subjects comprised 44 patients with histologically proven lung cancer (squamous cell carcinoma (SCC), n=18; well-differentiated adenocarcinoma (WDA), n=9; poorly/moderately differentiated adenocarcinoma (non-WDA), n=17) who underwent (18)F-FDG-PET/CT examinations at 1, 2 h and 3 h after injection of 185 MBq of (18)F-FDG, approximately. Mean standardized uptake value (SUV) in each lesion was measured at each time point and the increase rate of SUV (IR_SUV) was calculated. SUV and IR_SUV were compared among the 3 groups. In addition, to estimate differences in kinetic parameters for each group, kinetic analysis based on a 3 compartment model was performed. Our results showed SUV differed significantly at every time point among the 3 groups. IR_SUV between 2 and 3 h post-injection (IR_SUV (2-3)) differed significantly among the 3 groups, while both IR_SUV(1-3) and IR_SUV(1-2) were significantly higher in SCC than in WDA. In kinetic analyses, both K1 and k3 showed significant differences among the 3 groups, with highest values in SCC and lowest in WDA. In conclusion, (18)F-FDG-PET 3-point imaging and kinetic analysis enabled the differentiation of histological subtypes in lung cancer, arising from differences in glucose transporter density and enzymatic activity of hexokinase. PMID- 22087440 TI - Serum differential proteomics analysis between papillary thyroid cancer patients with 131I-avid and those with non-131I-avid lung metastases. AB - Our aim was to compare the differences in serum protein fingerprints between papillary thyroid carcinoma (PTC) patients with (131)I-avid lung metastases and those with non-(131)I-avid lung metastases, and to establish a screening model for screening (131)I uptake in lung metastases. We collected serum samples from 46 PTC patients with (131)I-avid lung metastases (Group A) and 23 PTC patients with non-(131)I-avid lung metastases (Group B) respectively, and both groups were matched for age and sex, without history of other tumors. Among them, 28 cases (19 cases in Group A, and 9 cases in Group B) were enrolled in the training set to establish the decision tree model, and another 41 cases (27 cases in Group A, and 14 cases in Group B)were incorporated for blind test set. The serum protein fingerprints were profiled using surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS, USA) and the difference between the two groups was compared using the Ciphergen Proteinchip 3.1 software. Bioinformatics analysis was performed to construct the decision tree model based on the data of the training set, and the blind test was also conducted for blind test set. Our results showed that a total of 151 valid protein peaks were detected at the molecular range of 1300 Da to 15,000 Da, among which 7 were significantly different between Group A and Group B (P< 0.05). The blind test was conducted via the decision tree model, with a sensitivity of 92.6% (25/27) and a specificity of 85.7% (12/14). In conclusion, the difference in the serum protein fingerprints between Group A and Group B is quite accurate for screenning (131)I uptake in the lung metastases from PTC, conferring important clinical value for the prediction of (131)I uptake and guiding of personalized (131)I treatment decisions. PMID- 22087441 TI - Ventricular ejection fraction in patients with dilated cardiomyopathy calculated by gated blood pool SPET processing software: correlation with multigated acquisition and first pass radionuclide ventriculography. AB - This study was performed to find out the left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) in patients with dilated cardiomyopathy (DCM) by using commercially available automated gated blood pool scintigraphy (GBPS) processing software and to correlate it with first pass radionuclide ventriculography (FPRNV) and planar multigated acquisition (MUGA). However, till date, no literature exists studying the application of GBPS and planar radionuclide ventriculography techniques in the setting of patients with DCM as a single cohort. Forty-one patients having DCM were prospectively included in the study. First pass RNV and MUGA were performed at rest after in-vivo labeling of red blood cells in all patients. Immediately after obtaining the planar views, GBPS was performed and LVEF and RVEF were calculated. Our results showed that the %LVEF values (mean+/-SD) calculated by MUGA, GBPS and echo cardiography were 31+/-11, 34+/-12 and 32+/-11, respectively. The % RVEF values (mean+/-SD) calculated by FPRNV and GBPS were 46+/-14 and 43+/-17, respectively. The LVEF values calculated by MUGA, GBPS and echcardiography showed very good correlation r=0.924 and r=0.844, respectively and for both P <0.0001. Bland Altman plot showed overestimation for LVEF (and a tendency for overestimation of RVEF) values calculated by GBPS compared to MUGA. Values of RVEF calculated by GBPS and FPRNV also showed good correlation (r=0.88; P< 0.0001). In conclusion, the automated GBPS for LVEF and RVEF calculation using GBPS SPET can be routinely applied in DCM patients. Given the practical difficulties with FPRNV like good bolus administration, quantitative blood pool SPET (QBPS) can be used to calculate RVEF. Similarly MUGA and GBPS can be used to calculate LVEF. PMID- 22087442 TI - Does the association of 18F-FDG uptake intensity and lesion topography reveal histological phenotype and tumor differentiation in esophageal cancer? AB - In daily clinical practice, the esophageal squamous cell cancer (ESCC) is considered to be more (18)F-FDG avid than adenocarcinoma (EAD). To date, the few studies concerning the existence of a real metabolic difference based on esophageal cancer (EC) histology, show divergent and not definitive results. A retrospective analysis of (18)F-FDG PET/CT of 87 patients with ESCC and EAD was performed to investigate the role played by both histopathological subtype and tumor differentiation in the characterization of glucose metabolic profile of EC. Esophageal squamous cell cancer was well differentiated (WD) in 42 cases and poorly differentiated (PD) in 12 patients. Twenty-one of the 33 patients had WD EAD, while 12 had a PD EAD. The (18)F-FDG maximal standardized uptake value (SUV(max)) was determined for all lesions and used for inter and intra-group comparison. In ESCC, the SUV(max) ranged from 4 to 31 with a mean value of 16+/ 6. In EAD, the SUV(max) ranged from 2 to 25 with a mean value of 10+/-6. A statistically significant difference (P<0.0001) was found between ESCC and EAD. According to histological classification and tumor differentiation, we obtained the following results: a) the SUV(max) values of WD ESCC and WD EAD were 17+/-5 (range: 7-31) and 7+/-3 (range: 2-12) respectively (P<0.00001), b) the SUV(max) values of PD ESCC and PD EAD were 11+/-4 (range: 4-19) and 17+/-6 (range: 7-25) respectively (P<0.05). Moreover, a statistically significant difference of SUV(max) values was found between WD and PD ESCC (P<0.005) as well as between WD and PD differentiated EAD (P<0.0001). In order to predict tumor histology (ESCC, EAD) from both SUV(max) and lesion location, a multivariate discriminant analysis was performed on the whole population with a resulting diagnostic accuracy equal to 82% (P<0.00001). In conclusion, we provide additional arguments about (18)F FDG uptake difference between ESCC and EAD as well as between poorly and well differentiated forms of both EC histological subtypes. PMID- 22087443 TI - Prospective evaluation of technetium-99m ECD SPET in mild traumatic brain injury for the prediction of sustained neuropsychological sequels. AB - Our aim was to evaluate whether single photon emission tomography (SPET) versus computed tomography (CT) in acute phase of mild traumatic brain injury (MTBI) was better for the prediction of sustained neuropsychological symptoms beyond a typical recovery period. Forty five patients with MTBI were prospectively evaluated with clinical and neuropsychological exams, structural imaging using CT and perfusion study by(99m)Tc-ethylene cysteinate dimer ((99m)Tc-ECD) SPET within a week of the head trauma. After an interval ranging from 6 to 12 (median: 9) months, all patients were re-evaluated by standard neuropsychological tests for the assessment of sustained personality changes, imbalance and memory deficits. Our results showed that, 25 patients had abnormal brain perfusion on (99m)Tc-ECD SPET. In 19 cases of total 20 normal (99m)Tc-ECD SPET studies, no sign of memory deficit and imbalance was observed. Negative predictive value (NPV) for both complications was 95%. NPV of CT for the prediction of memory deficit and imbalance were 77.4% and 90.3%, respectively. The risk of developing sustained memory deficits and imbalance in patients with positive (99m)Tc-ECD SPET were 40% and 20%, respectively. A perfusion abnormality on (99m)Tc-ECD SPET was associated with a greater chance of long-standing memory deficits (odds ratio=13.49, P=0.020)while neither CT nor (99m)Tc-ECD SPET could independently predict the personality changes in these patients. The patients with abnormalities on both CT and SPET images faced a significant relative risk of complications, 1.63 times, higher than the others. In conclusion, our study indicated that (99m)Tc-ECD SPET imaging or CT imaging alone, could not predict the occurrence of sustained complications after MTBI. Concurrent use of both imaging modalities performed shortly after MTBI may yield the best results, as the combination of abnormalities in both cerebral structure and perfusion could indicate the patients with 1.63 times higher risk of sustained memory deficits, personality changes and imbalance. PMID- 22087444 TI - Effectiveness of radiosynoviorthesis in the treatment of chronic synovitis of small and middle-sized joints affected by rheumatoid arthritis. AB - Our aim was to describe and evaluate our experience in the treatment of radiosynoviorthesis (RSO) of small and middle-sized joints in patients with rheumatoid arthritis (RA). Eighty six patients with RA enrolled in the study. The criterion for enrolment was destructive process of the joint detected by X rays and classified as a stage II-III according to Larsen. Seventy-six middle sized joints were treated each with 74MBq or rhenium-186 sulphate and other 80 small joints with 10-40MBq of erbium-169 citrate each. The effect of treatment was evaluated at 6 and 12 months following the RSO treatment. The obtained values were compared with those of the initial state. The inflammatory and structural changes in activity were assessed according to the results of ultrasound examination, regression of pain, swelling of the joint and the improvement in mobility. The data obtained were statistically processed with the Chi-square test. Our results showed that RSO significantly decreased pain of the affected joints, however the influence upon joint motion was minimal. The best treatment results were observed in shoulders and elbows, while the ankles were the worst to respond to the RSO treatment. The significant (P<0.05) beneficial effect of the RSO treatment on pain and swelling reduction were only transient started on 1 week to 1 month and declined over 12 months. In conclusion, our study showed that RSO is a suitable alternative in the treatment of chronic synovitis, with a low potential of adverse effects. However the beneficial effect on pain and swelling reduction was only transient and declined over 12 months. PMID- 22087445 TI - Evaluation of diagnostic performance of 18F-FDG-PET compared to CT in detecting potential causes of fever of unknown origin in an academic centre. AB - Determining the cause of fever of unknown origin (FUO) often proves challenging to attending physicians and the role of conventional imaging in this setting has been uncertain. In this retrospective study, we examined the role of fluorine-18 fluorodesoxyglucose-positron emission tomography ((18)F-FDG-PET) compared to computed tomography (CT) in diagnosing the potential etiology of FUO. To accomplish this task, we identified patients with FUO who underwent (18)F-FDG-PET for detecting the source of fever. Twenty-four patients (16 males and 8 females, age range = 17-80, mean age = 49.5) were examined with (18)F-FDG-PET of which 18 were also assessed with a diagnostic CT (within 3 weeks, mean interval = 7.5 days). The PET and CT findings were reviewed and the presence of focal (18)F-FDG uptake or gross CT lesions was considered a potential site causing FUO. Of patients who underwent PET alone, 5/6 were reported as positive. Of the 18 who had both PET and diagnostic CT, PET was positive in 18 and CT was positive in only 7 cases. Of positive findings on PET, etiologies included infection (11), non-infectious inflammation (8), lymphoma (3), and other cancers (1). Of positive findings on CT, etiologies included infection (3), lymphoma (1), non-infectious inflammation (2) and other cancers (1). Importantly, we found no cases with positive CT and negative PET findings. In conclusion, accordingly to our findings, (18)F-FDG-PET appears to be of great value in assessing patients with FUO, especially when caused by infection or inflammation. Fluorine-18 FDG-PET is more sensitive than diagnostic CT in detecting and localizing diseased sites, and is the optimal imaging modality to evaluate patients with FUO. PMID- 22087446 TI - Imaging myocardial inflammation of various etiologies with 99mTc-depreotide SPET/CT. AB - Previous reports suggested the accumulation of technetium-99m-depreotide trifluoroacetate ((99m)Tc-D) at the sites of active infection or inflammation. Binding of depreotide to over-expressed somatostatin receptors in activated lymphocytes and macrophages probably accounts for the depiction of inflammation. We speculated that myocardial inflammation could also be illustrated by (99m)Tc-D scintigraphy. We report on 3 patients with the clinical diagnosis of myocarditis of various etiologies, in which (99m)Tc-D SPET/CT demonstrated obvious tracer uptake in the myocardium of the left ventricle. In conclusion, we suggest that depreotide imaging can depict myocardial inflammation, thus supporting clinical diagnosis. PMID- 22087447 TI - Sensitivity of PET/MR images in liver metastases from colorectal carcinoma. AB - Our aim was to evaluate the sensitivity of positron emission tomography/magnetic resonance image (PET/MRI) in the detection of liver metastases in patients from colorectal cancer as compared with computed tomography (CT), magnetic resonance imaging (MRI), PET and PET/CT images. From April 2008 to April 2010, twenty-four patients (mean age 56.5+/-10.5 years) with liver metastases from colorectal cancer diagnosed by pathology were retrospectively studied as above. All image data were respectively collected and fused. PET/CT and PET/MRI fusion images were successfully performed with a PET-MR-CT robot transmission-fusion imaging system. Pathologic findings and clinical follows-up were performed as referenced standards. Images were reviewed independently by at least three experts. We found a total number of 121 metastatic lesions and 35 of them, with a maximum diameter less than 1cm. According to a per-lesion analysis, the sensitivity on liver metastases was 64.5%, 80.2% and 54.5% on CT, MRI and PET, respectively. Based on reconstruction imaging analysis, PET/CT and PET/MRI showed sensitivities of 84.2% and 98.3%. Sensitivity comparison of PET/MRI had superior sensitivity of 98.08%. Paired data analysis (McNemar) resulted a type I error which equated to 0.05. There was a statistically significant difference between CT and MRI or PET for the detection of patients with liver metastatic lesions (P<0.05). However, PET/MRI can efficiently detect more metastatic lesions than PET/CT (P<0.05) among those with diameter <1cm. In conclusion, PET/MRI was a quite efficient diagnostic modality compared to conventional imaging modalities and should be considered the procedure of choice in the detection of liver metastatic lesions from colorectal cancer. PMID- 22087448 TI - Myocardial scintigraphy, echocardiography and proBNP for early detection of myocardial cardiotoxicity in breast cancer patients after chemo-radiotherapy. AB - The most severe side effect in breast cancer patients, treated with chemotherapy and/or radiotherapy is cardiotoxicity, leading to chronic heart failure and worsening the quality of life. The aim of our study was to detect early in these patients signs of cardiotoxicity. Twenty four breast cancer patients were included in our study after combined treatment (chemo and radiotherapy). We studied myocardial function by gated single photon emission tomography (GSPET MS), echocardiography (EC) and 32 amino acid polypeptide B-type natriuretic peptide (ProBNP) measurements. We found early signs of cardiotoxicity in 10/24 investigated patients. All patients had no clinical symptoms, and normal electrocardiogram and left ventricular ejection fraction (LVEF). According to results from the performed tests, patients were divided in 4 groups: a) Normal systolic and diastolic LV function, normal ProBNP value, normal myocardial scintigraphy in 14/24 patients. b) Diastolic dysfunction, increased ProBNP value, hypoperfused defects in myocardial scintigraphy in 5/24 patients. c) Diastolic dysfunction, normal ProBNP value, hypoperfused defects in myocardial scintigraphy in 3/24 patients. d) Normal systolic and diastolic LV function, normal ProBNP value, hypoperfused defects in myocardial scintigraphy in 2/24 patients. In conclusion, in patients with breast cancer and asymptomatic cardiotoxicity, by applying GSPET-MS, ProBNP measurements and EC diastolic function tests, we detected early signs of myocardial damage in 10/24 patients 6-12 months after chemotherapy and radiotherapy. PMID- 22087449 TI - (111)In-pentetreotide SPET/CT in carcinoid tumours: is the role of hybrid systems advantageous in abdominal or thoracic lesions? AB - Our aim was to evaluate the different clinical value of (111)In-pentetreotide hybrid SPET/CT versus SPET alone in detecting carcinoid tumours located in the thoracic and abdominal region. Twenty-four patients with carcinoid tumours histologically proven (13 of abdominal origin, 11 of thoracic origin) underwent (111)In-pentetreotide SPET/CT with hybrid system (Millennium VG with Hawkeye, G.E.M.S., USA) composed of a dual head gamma camera equipped with a low dose X ray tube. Single photon emission tomography images were performed 4h and 24h after (111)In-pentetreotide intravenous administration, while SPET/CT co registered images were performed at 4h. Scintigraphic images were first evaluated alone and then re-interpreted by adding transmission fused data. Nine of the 13 patients with tumours of abdominal origin showed pathological SPET images, while 4/13 were negative. Seven out of the 11 patients with tumour of thoracic origin had pathological SPET findings, while 4/11 were negative. In all, 11/24 subjects disclosed abdominal pathological uptake and 10/24 thoracic. In 6/11 abdominal cases SPET/CT allowed anatomical localization of lesions, while in 2/10 in thoracic cases. Additional data were provided by SPET/CT in 8/24 cases (6 abdominal, 2 thoracic), by transmission images characterized as lesions not expressing somatostatin receptors. Sensitivity of SPET alone in all carcinoids was 72%, negative predictive value (NPV) was 50% and accuracy was 78%. Considering abdominal lesions (independently of the origin) sensitivity of SPET alone was 64.7%, NPV was 40%, accuracy was 71.4%. For thoracic lesions sensitivity of SPET alone was 83.3%, NPV was 66.7% and accuracy was 87.5%. For SPET/CT considering together all carcinoids and also separately lesions of abdominal and of thoracic origin, sensitivity, NPV and accuracy were always 100%. In conclusion, SPET/CT imaging was more useful to anatomically detect carcinoids either in abdomen or in thorax and specifically lesions not expressing somatostatin receptors, as compared to SPET alone. PMID- 22087450 TI - Quantification and reduction of attenuation related artifacts in SPET by applying attenuation model during iterative image reconstruction: a Monte Carlo study. AB - Photon attenuation is one of the main causes of the quantitative errors and artifacts in SPET. A transmission or CT based attenuation map is necessary to correct for the effects of attenuation accurately. In this research, some important attenuation related artifacts are described. A fast and memory efficient iterative algorithm is proposed for attenuation correction. Ordered subset expectation maximization (OSEM) algorithm with attenuation model was applied for image reconstruction. Monte Carlo simulation was used to create the projections in this study. Different voxel based phantoms with uniform and non uniform activity distributions and attenuation maps were employed to evaluate the accuracy of this algorithm. The NCAT digital phantom was also used to investigate the attenuation effects on myocardial perfusion SPET in men and women. Projections free from the effect of attenuation were also simulated. The reconstructed image from these attenuation-free projections was considered as reference image. Our attenuation correction algorithm was evaluated by its ability to recover activity and to remove attenuation related artifacts. The mean-square-error (MSE) between reference and corrected image and image contrast were calculated for quantitative evaluation of this algorithm. A variety of attenuation related artifacts were observed. Moreover anterior wall of myocardial perfusion images of female phantom and inferior wall in male phantom were affected by attenuation. All of the attenuation related artifacts were removed after attenuation correction. Quantitatively, the MSE values between reference images and corrected images were reduced by about 900% for all phantoms. In conclusion, by applying our new method for incorporating attenuation model during OSEM, we were able to eliminate a variety of artifacts and errors, which is a necessary step for quantitative SPET. PMID- 22087451 TI - The diagnostic role of gated myocardial perfusion imaging and radionuclide ventriculography in severe congenital heart disease. AB - Several techniques have been applied for the assessment of severe congenital heart diseases (SCHD) including echocardiography, cardiac catheterization with angiocardiography, and more recently, cardiovascular multi detector tomography and magnetic resonance imaging (MRI). The value of gated single photon emission tomography (GSPET) myocardial perfusion imaging (MPI) and radionuclide ventriculography (RNV) for evaluating myocardial ischemia, tissue viability, and left ventricular function in SCHD is less apparent. The risk of radiation exposure is greatest in the youngest patients. Both, GSPET MPI and RNV seem to be underutilized in pediatric clinical practice due to increased radiation exposure. We have reviewed basic and specific technical and diagnostic aspects, as well as specific clinical indications of GSPET MPI and RNV in children with SCHD in comparison with other cardiology methods. Some of our own tests are also presented where they apply. In conclusion, GSPET MPI and RNV can provide clinical relevant information of functional significance of SCHD in pediatric patients especially when the other cardiology methods are indeterminate. With regard to radiation exposure appropriate patient selection and recommendations for reduction of radiation exposure are of great importance. PMID- 22087452 TI - Kummell's disease: pathophysiology, diagnosis, treatment and the role of nuclear medicine. Rationale according to our experience. AB - Kummell's disease (KD) is a rare clinical entity and includes patients, who after a trivial trauma and an asymptomatic period, develop a progressive vertebral body collapse and a painful kyphosis. The main pathologic eliciting event still remains unclear. Vertebral body collapse can be the result of infection, malignant neoplasia or trauma. It may be difficult to distinguish among them, particularly in osteoporosis. To explain the time lag between initial trauma and vertebral collapse, the hypothesis of ischemic necrosis was suggested. Many authors considering KD as a case of mere vertebral osteonecrosis have wrongly reported cases of osteonecrosis without a spinal trauma, as KD. The fact that intravertebral vacuum cleft often coexists with vertebral osteonecrosis further added to confusion. Various imaging modalities including bone scan support the diagnosis of KD. It is described that bone single photon emission tomography (SPET) or SPET/computed tomography scintigraphy using dynamic and static, acquisition can identify the chronicity of the lesions. PMID- 22087453 TI - (99m)Tc-DMSA scintigraphy diagnosing crossed renal ectopia with fusion in a three years old boy. AB - A 3 years old boy with a history of surgery for orchidopexy was admitted to our hospital with fever and abdominal pain. Clinical examination and laboratory investigations revealed urinary tract infection with renal involvement. Ultrasonography demonstrated a solitary left kidney and raised the suspicion of a fusion anomaly. Voiding cystography disclosed grade III vesicoureteral reflux and technetium-99m dimercaptosuccinic acid scintigraphy revealed right to left crossed renal ectopia with fusion (L-shaped kidney). The patient is undergoing standard follow-up for the early detection of possible renal complications. In conclusion, L-shaped kidney is a rare entity and the (99m)Tc-DMSA scintigraphy played an important role on timely diagnosis. PMID- 22087454 TI - Hashimoto thyroiditis: A "true" adenoma visualized as a hot nodule in the presence of overt hypothyroidism. AB - A 63 years old woman with Hashimoto's thyroiditis, on thyroxin treatment presented imaging studies concordant with a multinodular goiter, a "hot" nodule in the left lobe and partial suppression of the right lobe. After thyroxin withdrawal overt hypothyroidism developed, yet the patient's imaging studies were not altered. This is a case of hypothyroidism in a patient with Hashimoto's thyroiditis, multinodular goiter and a concomitant "hot nodule", showed on scintigraphy, as a functioning adenoma in a non functioning thyroid. This finding is quite rare as no specific percentages are mentioned in the literature. To our knowledge this is the first such case described in Greece. PMID- 22087455 TI - Detection by (18)F-FDG PET of unsuspected extensive bone marrow metastases in a case of basosquamous carcinoma of the cheek. AB - Basosquamous carcinoma (BSC) is a rare type of malignancy with features of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a potential for aggressive behaviour infiltration and destruction. First reported by MacCormac in 1910 in a series of rodent ulcers, this entity does have an increased risk of recurrence and metastases as well, which distinguish it from other forms of basal cell carcinoma. The overall incidence of basosquamous carcinoma ranges from 1.2% to 2.7%. An unusual case of basosquamous carcinoma (BSC) is presented where 18- fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) scan diagnosed unsuspected extensive metastatic disease in the bone marrow, which was further proven histopathologically. The patient was a 32 years old man with history of recently diagnosed basosquamous carcinoma of left cheek involving left lower eyelid and left eyeball. Contrast enhanced computed tomography(ceCT) of the head and neck demonstrated involvement of the left cheek skin by the malignancy along with erosion of zygomatic bone and phthisis bulbi of the left eye. The serum alkaline phosphatase was elevated (255units, normal range 50-150units). The patient was referred for (18)F-FDG PET, for disease status evaluation. The scan showed intense tracer uptake in the left zygomatic region, the site of known primary disease. Intense tracer uptake was noted in the multiple lesions of bone marrow of axial as well as appendicular skeleton. The scan appearance was highly suggestive of metastatic bone marrow involvement. A bone marrow biopsy was performed to confirm the scan findings. Guided by the (18)F-FDG PET scan findings, bone marrow biopsy was performed and metastatic basosquamous carcinoma was diagnosed. We believe this is the first reported case of basosquamous carcinoma where extensive metastatic bone marrow disease was diagnosed with the aid of (18)F-FDG PET. At first diagnosis, an advanced stage of BSC is often present. Due to its metastatic potential, extensive primary surgical resection of BSC, possibly completed by radiation or photodynamic adjuvant treatment is recommended. Given the aggressive nature of basosquamous carcinoma, whole body (18)F-FDG PET is very useful in diagnosing metastatic BSC. In conclusion, this is the first reported case of the use of (18)F-FDG PET study for diagnosing metastatic bone marrow disease in a patient with basosquamous carcinoma. PMID- 22087456 TI - Positive lymphoscintigraphy (ILS) and negative computed tomography for metastatic penile cancer. AB - Penile carcinoma usually occurs in older than 40 years men with an incidence in western communities of 0.5 to 1.6 per 100,000 men per year while in developing countries the rate is much higher in men. Extensive lymph node dissection of lymphatic inguinal metastases evident by inguinal lymphoscintigraphy (ILS) induces improved overall survival. A 75 years old male with penile squamous cell carcinoma stage pT2N0M0 of less than 2cm diameter, with tumor invasion of the penis corpora underwent partial penectomy with a 2-cm disease-free margin. Three months postoperation, computed tomography (CT) was negative for local recurrence or distant metastases. A dynamic ILS was performed after local anaesthesia and intradermal injection of 80MBq of (99m)Tc-nanocolloid at the lower edge of the left and right inguinal ducts. The lymphatic chain and a hot spot suggestive of a first draining lymph node appeared after 15min on the right inguinal region in the second zone according to Daseler mapping. The left inguinal area was negative for sentinel node (SN). In view of this finding an exploratory laparotomy was performed and pathology showed that this lymph node that was probably a SN was infiltrated by the squamous cell carcinoma. The patient was upstaged to T2N1M0 and scheduled to receive adjuvant chemotherapy with two courses of cisplatin and 5-fluorouracil. While T1 and T2 tumours of diameters <2cm are best treated with penile-preserving methods such as circumciand/or local excision. Tumours of T2 >2cm, T3 tumours, and T4 tumours are treated with glans amputation and/or partial or total penile amputation. Imaging with magnetic resonance imaging (MRI) or computed tomography (CT) scan do not always give accurate staging information, because positive findings are usually found only in patients with clinically palpable, enlarged inguinal lymph nodes. Computed tomography and MRI have low sensitivity to identify occult metastases, because they present criteria for malignant involvement mainly based on the size of the lesions. The main pitfall of these diagnostic modalities is due to occult metastatic disease occurring within normal sized nodes. Approximatively 20% of the patients with non palpable lymph nodes harbour occult inguinal metastases, and there is evidence that this group of patients may benefit from early surgical dissection of the inguinal nodes, compared to a wait-and-see policy. It is understood that current imaging techniques cannot accurately detect occult metastases, while ILS is more reliable. In 80% of patients with penile cancer, after ILS, drainage to both groins is observed. Bilateral nodes are often visualized early, sometimes asynchronously with one of the lymph nodes filling late. This is why delayed images are recommended. Pitfalls of ILS are: a) Contamination of the skin with the tracer and b) radiopharmaceutical entering the blood. There are also several reasons that may account for absent or faint SN uptake: low dose of the tracer or low tracer quality, patient's age (better in young patients), tumor involvement of the sentinel node, and finally too short or too long interval between tracer injection and ILS. The ILS can be mapped according to Daseler's inguinal zones. Penile cancer drains directly to the nodes in the superior and central Daseler zones. According to others, the majority (73%) of SN was located in the medial superior, 8.7% in the lateral superior, and 18.3% in the central zone. No drainage was seen on the two inferior quadrants. The majority (62.1%) of higher-tier nodes was found in the external iliac zone. Inguinal LS can save us from watchful waiting in cases of otherwise occult metastases. In conclusion, ILS has shown lymph node metastases while clinical and CT examinations were negative. The false positive and false negative results of ILS are mentioned. PMID- 22087457 TI - (18)F-FDG positron emission tomography/computed tomography and (99m)Tc-MDP skeletal scintigraphy in a case of Erdheim-Chester disease. AB - Erdheim-Chester disease (ECD), first described by Jakob Erdheim and William Chester in 1930, is a rare form of non-Langerhan's cell histiocytosis with unknown aetiology, is charaterized by systemic xanthogranulomatous infiltrative disease. To date, about 350 cases of ECD have been described in the medical literature. The typical ECD diagnostic triad is bone pain, diabetes insipidus and bilateral exophthalmos. A 24 years old man came at our attention for polydipsia with nocturnal and diurnal polyuria, anorexia, febrile episodes (38(o)C), and arthromyalgia especially in the knees. Physical examination showed bilateral periorbital xanthelasma. Blood exams showed increase of plasma osmolarity, haematocrit, sodium and urea and decrease of potassium. Urine exams showed just decreased urine specific gravity, (1.001;normal range: 1.010-1.030) suggestive for central diabetes insipidus (CDI). Brain magnetic resonance with gadolinium enhancement showed the presence of multiple hyperintense lesions expecially in neurohypophysis (swollen and with markedly contrast enhancement). All these data raised the suspision of neurosarcoidosis, so a chest and abdomen contrast enhancement computed tomography was performed, which didn't show abnormalities, making less possible the diagnosis of sarcoidosis. Two weeks later, whole-body (from head to pelvis) plus lower limbs 18-fluorine-labelled 2 deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography ((18)F FDG PET/CT) was performed. Uptake of (18)F-FDG was observed in the upper portion of the midbrain area (SUV(max) 7.1) and the pituitary gland (SUV(max) 7.3), and diffuse bone marrow uptake of (18)F-FDG in the proximal epiphysis and metaphysis of both humeri and thigh bones (SUV(max) 6.5), shoulder blades, pelvis bones and the L2 vertebral body (SUV(max) 3.9). This (18)F-FDG PET/CT confirmed the presence of brain lesion seen in MRI , the absence of visceral lesions, but also showed the presence of an atypical bone uptake of (18)F-FDG, leading to the suspision of ECD. A technetium-99m-methyl-diphosphonate skeletal scintigraphy ((99m)Tc-MDP) scan showed diffuse uptake of the radiopharmaceutical, in the diaphysis of long bones and in the left portion of the body and the spinous process of L2. Considering the difficulties of an osteomedullary or brain biopsy, biopsy was performed on a right anterior thoracic cutaneous xanthelasma. Histology showed lipid-laden histiocytes (CD1a-, CD68+, S-100 protein -) with small nuclei, Touton giant, lymphocytic infiltrates, eosinophils and fibrosis, ECD gold standard patterns as reported in literature. The patient was discharged with the diagnosis of ECD with central nervous system (CNS) manifestations, and treatment started. The diagnosis can be lead by the most charateristic bone findings of symmetrical osteosclerosis of the long bones, especially the lower limbs (tibia and fibula), involving metaphyses and diaphyses but sparing epiphyses. The typical pattern of osteoscerosis of the long bones reflects increased osteoblastic activity. About half of all ECD patients may experience extraskeletal manifestations, including CNS. Visceral involvement in ECD is not specific, and this enforces the diagnostic value of skeletal imaging findings. Furthermore xanthomas can be found at any location on the skin, especially the eyelids as in our patient. For visceral involvement, CT is most useful, while MRI is more sensitive for CNS lesions. Involvement of CNS may be frequently revealed clinically by diabetes insipidus. Few case reports have shown that (18)F-FDG PET/CT scanning could be useful in assessing the extension of ECD lesions. Both radiography and (99m)Tc-MDP skeletal scintigraphy may reveal osteosclerosis of the long bones, which is a typical finding in ECD. The typical bone pattern of (18)F-FDG PET/CT scan is specific for ECD and (99m)Tc-MDP skeletal scintigraphy may be performed in patients in whom initial (18)F-FDG PET/CT scans present the possibility of ECD diagnosis. Others reported that (18)F-FDG PET/CT scans had good sensitivity (66.7%) and specificity (92.3%) as compared with MRI of the CNS involvement or lesions. In conclusion, the (18)F-FDG PET/CT scan and the (99m)Tc MDP scan depicted many of the most relevant lesions of ECD for the initial assessment of ECD in our patient. PMID- 22087458 TI - Comparison between one day and two days protocols for sentinel node mapping of breast cancer patients. AB - Sentinel node biopsy can decrease the morbidity of breast cancer treatment significantly by sparing many patients of axillary lymph node dissection and resulting arm lymphedema. Despite widespread use of sentinel node mapping for breast cancer patients almost all aspects of this procedure are controversial; such as: type of the radiotracer, eligibility, time of injection, etc. One of these controversial issues is the efficacy of 2 days protocol (injection of the tracer on one day and sentinel node mapping and surgery on the following day). The main reason to perform 2 days protocol is the ease of operation room scheduling the patient does not need to complete injection and imaging in the nuclear medicine department. Despite widespread use of 2 days protocol for sentinel node mapping, very few studies have specifically evaluated this protocol in comparison to 1 day protocol and also the false negative rate which is the better index of sentinel node mapping success. Most of the above studies used tracers with large particle size such as (99m)Tc-sulfur colloid. Tracers with small particle size can theoretically be washed out from the real sentinel nodes and move to the second echelon nodes, so some recommended using large particle size radiotracers for the 2 days protocol. In this study, we compared the false negative rate of sentinel node mapping between 1 and 2 days protocols using intradermal injection of (99m)Tc-antimony sulfide colloid ((99m)Tc-SbSC) which has very small particle size. Eighty patients with early stage breast cancer (clinical stages of I and II) were evaluated. The diagnosis of the breast cancer was established by either excisional or core needle biopsy. The patients didn't take any chemotherapeutic drug before surgery and were divided into two groups: 1 day (Group I) and 2 days (Group II) protocols (45 in Group I and 35 in Group II). For Group I, periareolar intradermal injections of 0.5Bq/0.2mL (99m)Tc-SbSC were applied for patients without previous excisional biopsy. For patients with excisional biopsy two intradermal injections of 0.5Bq/0.2mL (99m)Tc-SbSC were used on both sides of the incision line. All injections were followed by gentle massage for 1min. For Group II, the same injection techniques were used but the dose of the tracer was doubled. Anterior, and lateral spot views were acquired 30min after the injection (5min/image, 128Chi128 matrix) using a dual head gamma camera (E.CAM Siemens) and parallel hole low energy high resolution collimator. The operation was performed 4h (for Group I) or 20h (for Group II) post radiotracer injection. All patients received 2mL patent blue V dye in a subdermal and periareolar fashion, 2min after general anesthesia. A surgical gamma probe (EUROPROBE, France) was used for harvesting the sentinel lymph nodes during surgery. As sentinel node was defined any blue node or any node with an ex vivo radioisotope count of twofold or greater than the axillary background. After completion of sentinel node biopsy, all patients underwent standard axillary lymph node dissection. The study was approved by our local ethical committee and all patients gave their informed consent before inclusion into the study. Quantitative data were expressed as mean+/-SD. For comparison between groups, independent sample student's t-test for quantitative variables, and chi-square or Fisher's exact tests for categorical variables were used. P-values less than 0.05 were considered statistically significant. SPSS version 11.5 was used for statistical analyses. The patients characteristics are shown in Table I. These general characteristics were not significantly different between the study groups (P>0.05). Detection rate was 100% for both Groups. The median number of sentinel nodes in both Groups was one sentinel node. The mean number of detected sentinel nodes during surgery was not statistically different between groups (1.28+/-0.7 and 1.32+/-0.6 for Group I and II respectively). One false negative sentinel node case with positive axillary nodes after dissection was found in both groups. This amounts to 6.25% and 6.66% false negative rate for Group I and II patients respectively. During surgery mean count rate at the injection site was 243123+/-22134 and 29430+/-2125 for Groups I and II, respectively. Mean count rate at the sentinel nodes was 4345+/-457 and 2375+/-356 for Groups I and II, respectively. Although the mean count rate at the injection site and the sentinel nodes were both higher in Group I of the study compared to Group II (P<0.0001 for both), the mean ratio of sentinel to injection site was statistically higher in Group II (P<0.0001). The 2 days protocol allows that the required lymphoscintigraphy imaging (including delayed views) can be performed before and during operation without any time limits. Most studies have reported similar to ours detection or false negative rates for both protocols. Our study showed comparable mean number of harvested sentinel nodes by the two protocols which is against the hypothesis of moving the tracer to other sentinel nodes by time. Others had similar results. The count rate of the sentinel nodes during surgery was statistically acceptable. Similar results have been reported by others too. Although we didn't evaluate radiation exposure in our study, this was acceptable in other studies and Buscombe et al showed a maximum effective dose of 2.6MUSv/MBq for these patients and even assuming this highest value the patient exposure was very low compared to many other procedures. In conclusion, two days protocol gives the sentinel node biopsy team considerable flexibility and lymphoscintigrpahy imaging can be completed before surgery. Finding of the axillary sentinel node during surgery is also being easier. False negative rates as well as the detection rate for one day and two days protocols are comparable. PMID- 22087459 TI - A first described chest wall metastasis from colon cancer demonstrated with (18)F FDG PET/CT. AB - It is well known that, haematogenous colon cancer metastases are most commonly found in the liver, less likely in the lungs through the paravertebral venous system and rarely in other organs. Sporadic clinical cases of colon cancer metastases to the abdominal wall, the thyroid or the adrenal glands have been reported. Here, we present an uncommon case of chest wall metastasis from colon cancer demonstrated with 2-fluoro [fluorine-18]-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT). A 52 years old female patient was examined after she felt a swelling mass above her left breast. Tumor makers, such as serum cancer embryonic antigen (CEA) 146.22kU/L (normal range:0.00~37.0kU/L) and CA19-9 (258.16MUg/L (normal range:0.00~10.0MUg/L) and neuron-specific enolase (NSE) 78.2 (normal range: 0.00~17.00) were abnormally high. Chest CT revealed the soft tissue density mass on the left anterior chest wall with invasion of left 4th rib, and CT-guided biopsy showed a poorly differentiated adenocarcinoma of unkown origin. The patient was then referred for the (18)F-FDG-PET scan which was performed one hour after the intravenous injection of 370MBq of (18)F-FDG (Discovery Camera, VCT, GE, USA) and showed in addition to the chest mass, abnormal (18)F-FDG accumulation in both lungs, left supraclavicular and peritoneal lymph nodes. Furthermore, high (18)F-FDG uptake was detected in the sigmoid. Pathology findings from colonoscopy confirmed that this was a sigmoid colon adenocarcinoma. So far, chest wall metastasis from colon cancer as an initial finding has not been reported. Usually, an initial chest wall mass is hardly suspected to be a colon cancer metastasis. Abnormal serum tumor markers such as CEA and CA19-9 supported the diagnosis of a gastrointestinal adenocarcinoma. In our case, we found high serum NSE and normal findings of bowel wall on the CT scan, thus without the positive (18)F-FDG findings, one would probably consider as first diagnosis: chest wall metastasis from lung cancer, or a neuroendocrine tumor. The unusual finding in this case was that on the CT images there was no obvious local density of the intestine, no bowel wall thickening, or suspicious nodular lesions. Segmental (18)F-FDG accumulation seen in the sigmoid colon had early maximum standardized uptake value (SUV(max)) 7.3 and in 1h delayed estimation, 8.1. Colonoscopy showed that the (18)F-FDG-avid area at the colon was circular and thickened. "Hot" lesions found in both lungs, the supraclavicular and retroperitoneal lymph nodes by (18)F FDG PET/CT scan were considered to be most probably metastases from colon adenocarcinoma. In conclusion, PET as a rather simple procedure and less dependent on bowel preparation diagnosed the primary colon cancer, its metastases and specifically a first described chest wall metastasis, while CT alone did not show the primary tumor. PMID- 22087460 TI - Can pain influence the severity of findings of an (18)F-FDG PET/CT scan in loosening hip arthroplasty? AB - Pain is a common symptom after loosening and/or after infection of arthroplasty. The aim of the present case report is to indicate that fluorine-18-fluorodeoxy glucose positron emission tomography/computerized tomography((18)F-FDG PET/CT) scan can be used for the evaluation of pain at the site of arthroplasty with a semi quantitative measurement. An 84 years old male patient, with a history of papillary thyroid cancer was referred to our Nuclear Medicine Department for an (18)F-FDG PET/CT scan for evaluation of his metastatic disease. He reported right hip prosthesis thirty years ago and now suffered from significant pain in the right hip joint which on a scale from 1 to 10 could be rated as grade 8. White blood cell count, sedimentation rate and C-reactive protein were within normal limits. Four years ago he also had severe pain on the right leg that could be rated as grade 8, and underwent an (18)F-FDG PET/CT scan that showed a maximum standardized uptake value (SUV(max)) of 9.8. A year later, at a follow up (18)F FDG PET/CT scan and under a similar severe pain, SUV(max) was 10. The patient had a hip prosthesis in the left leg 3 years ago, for which he reported pain that could be rated as grade 3 and the SUV(max) was then 3.7. The degree of (18)F-FDG uptake is related to cellular metabolic rate and to the number of glucose transporters. In inflammation, the activated inflammatory cells demonstrate increased expression of glucose transporters and the affinity of glucose transporters for deoxyglucose is increased by various cytokines and growth factors. Furthermore, when the mononuclear cells and the granulocytes are activated by certain infectious humoral stimuli, they use large amounts of glucose by the hexose monophosphate shunt and the rate of oxygen uptake is intensely increased, during the so called "respiratory burst". In the present case, it was interesting to note that the degree of (18)F-FDG uptake at the sites of loosening hip arthroplasty was related to the severity of pain. Signs of infection or inflammation although not obvious in our case, could not be excluded because sensitivity, specificity and accuracy of PET for detecting infection associated with hip prostheses has been reported to be, 90%, 89.3% and 89.5%, respectively and sensitivity and specificity for detecting periprosthetic inflammation 100% and 45.5%,respectively. In another study using as a criterion for periprosthetic infection the increased (18)F-FDG activity at the bone prosthesis interface of the femoral component, sensitivity, specificity, positive and negative predictive values for the (18)F-FDG PET study where 85%, 93%, 80% and 95%, respectively. Inflammation, often intense, may be present in aseptic loosening and characterized by increased periprosthetic (18)F-FDG uptake. In conclusion, in our case the degree of (18)F-FDG uptake in a loosening hip arthroplasty was related to the severity of pain although inflammation or infection could also play some role. Further studies are required to prove this suggestion. PMID- 22087461 TI - A pregnant woman with metastatic papillary thyroid carcinoma and paraplegia: Multiple considerations involved in the management. AB - A 35 years old primigravida hailing from a humble, rural background with no previous history related to thyroid carcinoma, presented with acute paraparesis at the last trimester of pregnancy and was diagnosed to harbor metastatic papillary thyroid carcinoma (PTC) following magnetic resonance imaging (MRI) of the spine with guided biopsy, which demonstrated near complete collapse of D5 and D10 vertebral bodies with altered signal on the D4 to D6 and D9 to D11 vertebral bodies, in addition to a gravid uterus and a large goiter. There was also evidence of bilateral nodular lesions in the lung parenchyma and a fairly large hepatic lesion in segment 8 of the liver . Histopathology revealed metastatic follicular variant of thyroid papillary carcinoma. This case with challenging presentation had multiple issues to be resolved during its management: a) acute paraparesis and the requirement of radioiodine ((131)I) treatment soon after total thyroidectomy, b) her first valuable pregnancy that required to be managed successfully, c) the poor general condition, d) the abstinence from iodine containing medications, in relation to the Cesarean section planned, e) the timing of total thyroidectomy, f) postnatal care of the newborn and g) radioprotective measures. All were important considerations in the management of this patient. Iodine restricted diet and medications were recommended and were communicated to the obstetricians involved in the patient. The patient underwent Cesarean section and total thyroidectomy at the same sitting. The newborn baby was healthy and was started on artificial feeding. Recombinant TSH primed protocol was not considered immediately in view of a major surgery being undertaken and the poor general condition, so that the patient would not require frequent support during the isolation period. In the first 3 weeks of the postoperative period, she was put on T3 substitution and after a 2 weeks gap was given (131)I and whole body diagnostic scan was undertaken 48h after the administration of (131)I scan dose. Both the diagnostic and post (131)I treatment scan demonstrated multiple foci of (131)I uptake in the skeleton, lungs and liver. Following discharge from the isolation ward, adequate separation from the infant was ensured and the childcare was undertaken by relatives. The patient had a remarkable improvement clinically. During the next 3-1/2 years she was treated 2 more times with (131)I with cumulative doses of about 25.9GBq. The last post-treatment scan is depicted in. She has been presently ambulatory with complete resolution of paraplegia and a significantly better quality of life without any requirement of support, despite the presence of extensive skeletal disease. A recent review entitled "Approach to the pregnant patient with thyroid cancer", addresses this topic as a separate category. Similar emphasis has also been given by other authors while dealing with these patients. In our experience, patients with PTC metastatic lesions in the vertebrae show better response compared to those with large flat bone metastases likely related to the small size of the former. In conclusion, a teamwork of surgeons, obstetricians, nuclear medicine physicians as well as the strong support by the relatives, was necessary to favorably treat this patient with metastatic PTC, paraplegia and pregnancy. PMID- 22087462 TI - The half maximum time of (99m)Tc-DTPA renography measured in healthy kidney donors, compared to (131)I-OIH. AB - Technetium-99m-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) has been widely used after (131)I-ortho-hippurate ((131)I-OIH) for renography and to test renal function. Only a few reports refer to normal values range of (99m)Tc-DTPA renography half maximum time (HMT). We have measured the normal value range of (99m)Tc-DTPA renography HMT in our department, of 433 healthy kidney donors from 2007 to 2010, and compared these results with those of (131)I-OIH renography. There were 326 men and 107 women, 18y-69y (median age 29y), subjects were measured before the donation of their kidneys operation and their biochemical, ultrasound and renal function tests were normal. All subjects drunk at least 1 litre of tap water before renography. The (99m)Tc-DTPA dynamic scintigraphy was performed in the posterior view by injecting intravenously as a bolus 185-296MBq. Dynamic imaging was performed immediately after the injection, using a high resolution low-energy general purpose collimator and a large field of view dual detector gamma-camera (Hawkeye; General Electric Medical Systems, USA). Matrix was 64Chi64, the phase acquisition time of blood perfusion was 1s/frame and 30 frames were collected. Dynamic acquisition was 30s/frame and 39 frames were collected. Total acquisition time was 20min. We defined as background two regions of interest around the kidneys and the aorta, for radioactive decay correction. We also compared (99m)Tc-DTPA renography HMT values with the HMT values of (131)I-OIH, between the two kidneys, and between men and women. The findings were evaluated by using frequency distribution analysis, paired Sample Student's t-test and one sample t test, with a level of significance P<0.05. We used the SPSS 10.0 statistical software. Since values beyond a high boundary were regarded as unusual, we used the P(95), i.e. " 95% of HMT reference ranges value" to determine the medical reference range of values, as the HMT normal limit. This reference value is used especially when the data shows a skewed distribution. For the HMT (P(95) value), the normal reference values found between mean values of the left and the right kidney were: 10.76+/-4.14min and 10.89+/-4.55min, respectively and P=0.416, two tailed. For the left kidney HMT, there was no significant difference between men: 10.90+/-4.31min and women: 10.33+/-3.57min, (t=1.235, v=432, P=0.2186, two tailed), and similar findings were found between men's right kidney HMT: 11.02+/-4.89min and women's right kidney HMT: 10.49+/-3.32min, (t=1.253, v=266.59, P=0.211, two tailed). By comparing the mean value of (99m)Tc-DTPA renography HMT measured (10.76min, 10.89min) with the mean value of (131)I renography HMT that we found in the literature as referring to both left and right kidneys (4min). We found a significant difference (P=0.000, two tailed). Renography may be used to diagnose urinary tract obstruction, estimate the split renal function and is useful. PMID- 22087463 TI - Information about Macedonian medicine in ancient Greece. AB - Ancient Greek Macedonians were highly interested in the improvement of their physical and psychological health. At first, they worshiped the mythical god Asclepius and his daughter Hygieia. In at least 24 places in northern Greece, in Halkidiki, Thessaloniki, Kozani, Kavala, Thassos, Serres and other places, archaelogical findings were related to Asclepius. Macedonian kings were also interested in the development of medicine, for the sake of their fellow citizens and their soldiers. Characteristic examples are the close relations of Hippocrates with king Perdikas (5(th) century B.C.) and of Nicomachus (Aristotle's father being a physician) with king Amintas. Alexander the Great had as his personal physician, the famous physician Philippos of Acarnania. An incident between Alexander and Philippos of Acarnania shows the respect of Macedonian kings to their doctors: Alexander became ill after a bath in the frozen river Cydnus (near ancient Tarsus). At this time he received a letter from his general Parmenion for not to trust his physician. Alexander gave this letter to Philippos to read it and while Philippos was reading it and was rather frightened, he saw Alexander drinking the medicine he had given him. We may note that Alexander the Great as a student of Aristotle had a general education about medicine. Archaeological findings revealed two funerary monuments of physicians: a doctor from Thasos, who practiced in Pella as a public physician during the 3rd quarter of the 4(th) century B.C. and a physician named Alexander, who lived in the 1rst half of the 5(th) century A.D. The tomb of a third physician, probably a surgeon, excavated in Pydna, near mount Olympus (3(rd) century BC)also indicates the importance of physicians in Macedonia. Archaeological findings, like surgical knives, from the Hellinistic and Roman periods, found in the city of Veria, also showed the respect of Ancient Greeks to medicine and to their physicians. An example is the skeleton of a young woman with an anterior cranial hole found in Veria. This trauma was attributed to a delicate surgical operation, perhaps performed to alleviate endocranial pressure. PMID- 22087464 TI - [Medical behavior (deontology) towards our students, our colleagues, our patients and the society]. AB - In this paper we try to describe the importance of a dignified behavior of the physician to his students, colleagues, patients and the society. We come to the conclusion that even if the other party is not showing the best of behavior, the physician has not only the responsibility and the duty but it is very much for his own interest to show a dignified and useful behavior to others. This is the main route for having a good reputation which will help him better exercise his medical duties and offer him personal happiness. Jeremy Bentham, an English judge and philosopher formed the Greek word deontology to mean correct behavior stating that this behavior is morally useful and a source of pleasure. The codes of Hammurabi, of the Indian Ayr Veda, of the Egyptians, the teaching of Aristotle, Hippocrates and others also describe medical deontology. PMID- 22087465 TI - [Is major depression in middle-aged men correlated with bone density decrease? A study on Greek population]. AB - During the last 10 years there has been an increasing interest in studying the coexistence of osteoporosis and depression in the male population, due to the increased morbidity and mortality in the patients' life. The present retrospective study evaluates the effect of major depression on the bone density of Greek middle-aged men. By using the method of dual-energy X-rays absorptiometry (DEXA) we reviewed the bone mineral density (BMD) studies performed in the lumbar spine (LS) and/or femoral neck, in 97 men of the white race, aged 55 years with mean age+/-standard deviation (SD)= 65+/-10.6 years, and body mass index (BMI) 30.2+/-4. The patients were divided in two groups, based on the coexistence (Group A) or absence of major depression (Group B). In group A men, the incidence of osteoporosis was 34.8% and osteopenia 39.5%, while in group B the corresponding percentages were 9.3% and 42.6%. Statistically significant difference was observed in mean BMD between Group A (0.876+/-0.170) and Group B (0.961+/-0.136) at the level of P=0.008, and also in mean T score (-1.72+/-1.57 versus -1.06+/-1.17) at the level of P value: 0.02 in both groups, while the diagnosis of osteoporosis between the two groups was statistically significantly different too (P=0.001. Pearson R: 0.3, P=0.004). Furthermore, the model of multiple linear regression and ANOVA table revealed statistically significantly depression of 0.252 and 0.575 units in mean BMD value and mean T score respectively in man with major depression in comparison to a mentally healthy man of the same age and BMI (regression coefficient b, P< 0.02). In conclusion, we observed statistically significant difference in mean BMD and mean T score values between major depression and mentally healthy men. Moreover, almost triple relative risk for the development of osteoporosis was shown in men with depression as compared to mentally healthy men (RR: 3.8, P=0.02). Cortisone intake, hypertension and smoking were statistically independent factors for male depression and BMD. The clarification of the underlying interactive mechanism between major depression, sympathetic system activation, age and bone resorption is important. PMID- 22087466 TI - A portable total reflection X-ray fluorescence spectrometer with a diamond-like carbon coated X-ray reflector. AB - A diamond-like carbon (DLC) coated quartz glass sample holder is used in a portable total reflection X-ray fluorescence (TXRF) spectrometer. A spot area of a water sample on the DLC sample holder becomes smaller than that on a quartz glass sample holder usually used in TXRF analysis because DLC is more hydrophobic. Therefore, the use of the DLC sample holder enhances fluorescent X rays reaching a detector compared with the use of a quartz glass sample holder, leading to improvement in detection sensitivity. A detection limit of 28 pg is achieved for Cr in a river water sample when using the DLC sample holder. PMID- 22087467 TI - Gold patterned biochips for on-chip immuno-MALDI-TOF MS: SPR imaging coupled multi-protein MS analysis. AB - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of immuno-captured target protein efficiently complements conventional immunoassays by offering rich molecular information such as protein isoforms or modifications. Direct immobilization of antibodies on MALDI solid support enables both target enrichment and MS analysis on the same plate, allowing simplified and potentially multiplexing protein MS analysis. Reliable on chip immuno-MALDI-TOF MS for multiple biomarkers requires successful adaptation of antibody array biochips, which also must accommodate consistent reaction conditions on antibody arrays during immuno-capture and MS analysis. Here we developed a facile fabrication process of versatile antibody array biochips for reliable on-chip MALDI-TOF-MS analysis of multiple immuno-captured proteins. Hydrophilic gold arrays surrounded by super-hydrophobic surfaces were formed on a gold patterned biochip via spontaneous chemical or protein layer deposition. From antibody immobilization to MALDI matrix treatment, this hydrophilic/phobic pattern allowed highly consistent surface reactions on each gold spot. Various antibodies were immobilized on these gold spots both by covalent coupling or protein G binding. Four different protein markers were successfully analyzed on the present immuno-MALDI biochip from complex protein mixtures including serum samples. Tryptic digests of captured PSA protein were also effectively detected by on-chip MALDI-TOF-MS. Moreover, the present MALDI biochip can be directly applied to the SPR imaging system, by which antibody and subsequent antigen immobilization were successfully monitored. PMID- 22087468 TI - Fabrication and performance of a microfluidic traveling-wave electrophoresis system. AB - A microfluidic traveling-wave electrophoresis (TWE) system is reported that uses a locally defined traveling electric field wave within a microfluidic channel to achieve band transport and separation. Low voltages, over a range of -0.5 to +0.5 V, are used to avoid electrolysis and other detrimental redox reactions while the short distance between electrodes, ~25 MUm, provides high electric fields of ~200 V cm(-1). It is expected that the low voltage requirements will simplify the future development of smaller portable devices. The TWE device uses four interdigitated electrode arrays: one interdigitated electrode array pair is on the top of the microchannel and the other interdigitated electrode array pair is on the microchannel bottom. The top and bottom substrates are joined by a PDMS spacer that has a nominal height of 15 MUm. A pinched injection scheme is used to define a narrow sample band within an injection cross either electrokinetically or hydrodynamically. Separation of two dyes, fluorescein and FLCA, with baseline resolution is achieved in less than 3 min and separation of two proteins, insulin and casein is demonstrated. Investigation of band broadening with fluorescein reveals that sample band widths equivalent to the diffusion limit can be achieved within the microfluidic channel, yielding highly efficient separations. This low level of band broadening can be achieved with capillary electrophoresis, but is not routinely observed in microchannel electrophoresis. Sample enrichment can be achieved very easily with TWE using a device with converging electric field waves controlled by two sets of independently controlled interdigitated electrodes arrays positioned serially along the microchannel. Sample enrichment of 40-fold is achieved without heterogeneous buffer/solvent systems, sorptive, or permselective materials. While there is much room for improvement in device fabrication, and many capabilities are yet to be demonstrated, it is anticipated that the capabilities and performance demonstrated herein will enable new lab-on a-chip processes and systems. PMID- 22087469 TI - Porphyrin based porous organic polymers: novel synthetic strategy and exceptionally high CO2 adsorption capacity. AB - Iron containing porous organic polymers (Fe-POPs) have been synthesized by a facile one-pot bottom-up approach to porphyrin chemistry by an extended aromatic substitution reaction between pyrrole and aromatic dialdehydes in the presence of small amount of Fe(III). The Fe-POPs possess very high BET surface area, large micropores and showed excellent CO(2) capture (~19 wt%) at 273 K/1 bar. PMID- 22087470 TI - Current and future directions in frailty research. AB - The concept of frailty has been evolving dramatically for the past 30 years. Through its evolution, a variety of single and multidimensional models have been used to describe frailty. This article reviews the current literature related to the defining dimensions of frailty and identifies the gaps in the literature requiring additional research. A detailed literature review was performed to identify key dimensions and models currently being used to define frailty, classify interventions that have been developed to reverse frailty, and identify potential areas for future research within this field. Despite the large body of research defining the dimensions of frailty, no consensus exists on a comprehensive, operational definition. A standardized definition will be critical to design effective interventions at earlier stages along the continuum of frailty and interpret findings from evaluation studies. Identified gaps in the literature include studies supporting the utility of expanding the definition of frailty to incorporate social determinants, studies evaluating the role of obesity in the development of frailty, and the need for longitudinal studies for defining the pathways to developing frailty. This review highlights the need for an accurate definition of frailty and for longitudinal research to explore the development of frailty and evaluate the effectiveness of the frailty reversal interventions that may avert or delay adverse outcomes within this susceptible population. These future research needs are discussed within the context of the growing pressures to bring down health care costs, and the role of comparative effectiveness research and cost-effectiveness research in identifying interventions with the potential to help slow the growth of health care spending among the elderly. PMID- 22087471 TI - Plasmon coupling in silver nanocube dimers: resonance splitting induced by edge rounding. AB - Absolute extinction cross sections of individual silver nanocube dimers are measured using spatial modulation spectroscopy in correlation with their transmission electron microscopy images. For very small interparticle distances and an incident light polarized along the dimer axis, we give evidence for a clear splitting of the main dipolar surface plasmon resonance which is found to be essentially induced by cube edge rounding effects. Supported by discrete dipole approximation and finite element method calculations, this phenomenon highlights the high sensitivity of the plasmonic coupling to the exact shape of the effective capacitor formed by the facing surfaces of both particles, especially in the regime of very close proximity. PMID- 22087472 TI - Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles. AB - A series of monodisperse (45 +/- 5 nm) fluorescent nanoparticles from tri-block copolymers (polymeric nanoparticles (PNPs)) bearing different surface charges were synthesised and investigated for cytotoxicity in NR8383 and Caco-2 cells. The positive PNPs were more cytotoxic and induced a higher intracellular reactive oxygen species production than the neutral and negative ones. The cytotoxicity of positive PNPs with quaternary ammonium groups decreased with increasing steric bulk. The intracellular uptake and cellular interactions of these different PNPs were also tested in NR8383 cells by confocal laser scanning microscopy, which revealed higher uptake for positive than for negative PNPs. Also positive PNPs were found to interact much more with cell membranes, whereas the negative PNPs were internalised mainly by lysosomal endocytosis. Uptake of positive PNPs decreased with increasing steric bulk around the positive charge. A surface charge-specific interaction of clathrin for positive PNPs and caveolin receptors for negative PNPs was observed. These findings confirm that surface charge is important for the cytotoxicity of these PNPs, while they additionally point to considerable additional effects of the steric shielding around positive charges on PNP cytotoxicity. PMID- 22087473 TI - Establishment and application of event-specific polymerase chain reaction methods for two genetically modified soybean events, A2704-12 and A5547-127. AB - For implementation of the issued regulations and labeling policies for genetically modified organism (GMO) supervision, the polymerase chain reaction (PCR) method has been widely used due to its high specificity and sensitivity. In particular, use of the event-specific PCR method based on the flanking sequence of transgenes has become the primary trend. In this study, both qualitative and quantitative PCR methods were established on the basis of the 5' flanking sequence of transgenic soybean A2704-12 and the 3' flanking sequence of transgenic soybean A5547-127, respectively. In qualitative PCR assays, the limits of detection (LODs) were 10 copies of haploid soybean genomic DNA for both A2704 12 and A5547-127. In quantitative real-time PCR assays, the LODs were 5 copies of haploid soybean genomic DNA for both A2704-12 and A5547-127, and the limits of quantification (LOQs) were 10 copies for both. Low bias and acceptable SD and RSD values were also achieved in quantification of four blind samples using the developed real-time PCR assays. In addition, the developed PCR assays for the two transgenic soybean events were used for routine analysis of soybean samples imported to Shanghai in a 6 month period from October 2010 to March 2011. A total of 27 lots of soybean from the United States and Argentina were analyzed: 8 lots from the Unites States were found to have the GM soybean A2704-12 event, and the GM contents were <1.5% in all eight analyzed lots. On the contrary, no GM soybean A5547-127 content was found in any of the eight lots. These results demonstrated that the established event-specific qualitative and quantitative PCR methods could be used effectively in routine identification and quantification of GM soybeans A2704-12 and A5547-127 and their derived products. PMID- 22087475 TI - Proteomic and transcriptomic analyses of rigid and membranous cuticles and epidermis from the elytra and hindwings of the red flour beetle, Tribolium castaneum. AB - The insect cuticle is a composite biomaterial made up primarily of chitin and proteins. The physical properties of the cuticle can vary greatly from hard and rigid to soft and flexible. Understanding how different cuticle types are assembled can aid in the development of novel biomimetic materials for use in medicine and technology. Toward this goal, we have taken a combined proteomics and transcriptomics approach with the red flour beetle, Tribolium castaneum, to examine the protein and gene expression profiles of the elytra and hindwings, appendages that contain rigid and soft cuticles, respectively. Two-dimensional gel electrophoresis analysis revealed distinct differences in the protein profiles between elytra and hindwings, with four highly abundant proteins dominating the elytral cuticle extract. MALDI/TOF mass spectrometry identified 19 proteins homologous to known or hypothesized cuticular proteins (CPs), including a novel low complexity protein enriched in charged residues. Microarray analysis identified 372 genes with a 10-fold or greater difference in transcript levels between elytra and hindwings. CP genes with higher expression in the elytra belonged to the Rebers and Riddiford family (CPR) type 2, or cuticular proteins of low complexity (CPLC) enriched in glycine or proline. In contrast, a majority of the CP genes with higher expression in hindwings were classified as CPR type 1, cuticular proteins analogous to peritrophins (CPAP), or members of the Tweedle family. This research shows that the elyra and hindwings, representatives of rigid and soft cuticles, have different protein and gene expression profiles for structural proteins that may influence the mechanical properties of these cuticles. PMID- 22087476 TI - Preface. PMID- 22087474 TI - C-terminal tetrapeptides inhibit Abeta42-induced neurotoxicity primarily through specific interaction at the N-terminus of Abeta42. AB - Inhibition of amyloid beta-protein (Abeta)-induced toxicity is a promising therapeutic strategy for Alzheimer's disease (AD). Previously, we reported that the C-terminal tetrapeptide Abeta(39-42) is a potent inhibitor of neurotoxicity caused by Abeta42, the form of Abeta most closely associated with AD. Here, initial structure-activity relationship studies identified key structural requirements, including chirality, side-chain structure, and a free N-terminus, which control Abeta(39-42) inhibitory activity. To elucidate the binding site(s) of Abeta(39-42) on Abeta42, we used intrinsic tyrosine (Y) fluorescence and solution-state NMR. The data suggest that Abeta(39-42) binds at several sites, of which the predominant one is located in the N-terminus of Abeta42, in agreement with recent modeling predictions. Thus, despite the small size of Abeta(39-42) and the hydrophobic, aliphatic nature of all four side-chains, the interaction of Abeta(39-42) with Abeta42 is controlled by specific intermolecular contacts requiring a combination of hydrophobic and electrostatic interactions and a particular stereochemistry. PMID- 22087477 TI - Mechanism from isotope effects. AB - Abstract Isotope effects represent perhaps one of the most versatile tools available to investigators interested in the determination of reaction mechanism, particularly in the case of the mechanistic enzymologist. Interpretation of isotope effect data is somewhat more difficult for enzyme reactions, since the chemical or isotope-dependent step(s) is(are) normally not solely rate-limiting as they are for non-enzyme-catalyzed reactions. One can, however, take advantage of rate-limitation by multiple steps in an enzyme-catalyzed reaction to obtain information on a number of aspects of mechanism. In this paper, simple theory for the application of isotope effects to reaction mechanism is developed, and applied to organic reactions and those catalyzed by enzymes. Techniques used to measure isotope effects depend somewhat on the isotope used, that is radioisotope vs. stable isotope, or hydrogen isotope vs. heavier atoms. Techniques to be discussed include competitive and noncompetitive (or internal discrimination) measurements. In enzymecatalyzed reactions, information can be obtained on the order of addition of reactants and release of products, and this will be illustrated using the 6-phosphogluconate and alcohol dehydrogenase reactions. The use of multiple isotope effects can be used to distinguish between stepwise and concerted reactions, and this will be illustrated with the formate and glucose 6 phosphate dehydrogenase and malic enzyme reactions. PMID- 22087478 TI - Metabolite Pools and Metabolic Branching as Factors of in-vivo Isotope Discriminations by Kinetic Isotope Effects. AB - Abstract Inter- and intra-molecular non-statistical isotope distributions do not only require the existence of a kinetic isotope effect on a defined enzyme catalyzed reaction, but also the prerequisite that this reaction is located at a metabolic branching point. Furthermore a metabolic and isotopic balance demand that the extent of the isotopic shift is reciprocal to the products' yields. On this base the (13)C-enrichment of L-ascorbic acid in position C-1 and the depletion of glycerol in C-1 are interpreted. The (13)C-pattern of natural malic acid is discussed as a consequence of isotope effects on the carboxylation of pyruvate and PEP and on the pyruvate dehydrogenase reaction. The patterns of natural products synthezised by transfer of "active acetaldehyde" is proposed to be due to an isotope effect on the thiamine pyrophosphate containing lyase reaction. An isotope effect on the reduction of "active formaldehyde" to "active methyl" and the existence of corresponding pools is responsible for (13)C enrichments and depletions of natural products in positions bearing these intermediates. Finally a model for the main nitrogen pools and for isotope discriminations between alpha-amino, omega-amino-N and amide pools in plants is proposed. PMID- 22087479 TI - Isotope abundance ratios of sr in wine provenance determinations, in a tree-root activity study, and of pb in a pollution study on tree-rings. AB - Abstract In this contribution, the various and fundamentally different uses and applications of isotope signatures (of both heavy and light elements) are discussed. Examples are given for the successful use of (87)Sr/(86)Sr in uncovering fraud in wine trade. Also, in an experiment related to "Waldsterben", (87)Sr/(86)Sr analyses reveal rather unexpected responses of spruces and maple trees to mechanical damage of their roots. In another study, from (206)Pb/(207)Pb (and (208)Pb/(207)Pb) analyses of tree growth-rings it is demonstrated that they do not accurately record lead burdens in the environment. This is contrary to current views on the subject of tree-rings as reliable banks of past heavy metal pollutions of the biosphere. Furthermore, new perspectives of applications of isotopes in biological tissues, including those of cosmogenic and nucleogenic origin will be shortly outlined. PMID- 22087480 TI - The Effect of Diet Quality on delta(13)C and delta(15)N in the Tissues of Locusts, Locusta migratoria L. AB - Abstract Locust nymphs were raised from hatching to adult locusts on either seedling wheat (C(3)) or maize (C(4)), to determine whether relative enrichments/depletions of (15)N and (13)C within body tissues are influenced by diet. The maize contained less hexose sugars and protein per gram than wheat. The isotopic spacing between the food and the whole insect was found to differ between the two diets. The lower quality maize diet showed an overall +5.10/00 enrichment in delta(15)N compared to + 2.80/00 for wheat, possibly due to increased fractionation due to protein recycling. The maize diet resulted in increased depletion in lipid and trehalose and depletion in chitin relative to diet. The results for both delta(15)N and delta(13)C suggest that substrate recycling was occurring on the low quality maize diet. Therefore diet quality determines the enrichment/depletion in delta(15)N and delta(13)C within organisms. PMID- 22087482 TI - Sulfur isotopic composition of mangroves. AB - Abstract Sulfur isotope ratios of mangrove leaves of 19 species were compared to discuss the species-specific characteristics of sulfur uptake and assimilation. The members of Rhizophora and Bruguiera always show remarkable enrichments of the light isotope, giving negative delta(34)S values in most cases. The elaborated root systems of such species seem to be closely related to their sulfur absorbing systems as an adaptation to their anaerobic soil conditions. PMID- 22087483 TI - Dinitrogen fixation of microbe-plant associations as affected by nitrate and ammonium supply. AB - Abstract The dinitrogen fixation activity of Azospirillum sp., and Pantoea agglomerans strains was determined by (15)N(2) incorporation after incubation with (15)N(2) labeled air or/and by acetylene reduction. These bacterial strains were able to fix N(2) both in pure culture and in association with wheat plants in hydroponics. Nitrogenase activity of Azospirillum sp., in pure culture was more rapidly inhibited by the addition of NH(4) (+) than NO(3) (-). The N(2) fixation of P. agglomerans decreased only by NH(4) (+) -addition, but was stimulated by NO(3) (-). Nitrogen fixation in association with wheat plants remained unaffected by both N compounds. However, nitrogen derived from the atmosphere (N(dfa)) contributed only very little to the overall nitrogen nutrition of the plants. PMID- 22087484 TI - Determination of (13)C/(12)C-Ratios in Rumen Produced Methane and CO(2) of Cows, Sheep and Camels. AB - Abstract Naturally produced methane shows different delta(13)C-values with respect to its origin, e.g., geological or biological. Methane-production of ruminants is considered to be the dominant source from the animal kingdom. Isotopic values of rumen methane-given in literature-range between -800/00 and 500/00 and are related to feed composition and also sampling techniques. Keeping cows, camels and sheep under identical feed conditions and sampling rumen gases via implanted fistulae we compared delta(PDB) (13)C-values of methane and CO(2) between the species. Referring to mean values obtained from 4 or 5 samples at different times of 11 animals (n = 47) we calculated delta(PDB) (13)C-medians resulting in small but not significant differences within and significant differences between the species for CO(2) and methane. The delta(PDB) (13)C differences between methane and CO(2) were statistically equal within and also between the species. Therefore a linear regression of methane values on CO(2) is appropriate and leads to: delta(PDB) (13)C(methane)0/00 = 1,57 * delta(PDB) (13)C(CO(2))0/00-470/00 with a correlation coefficient of r = 0,87. PMID- 22087485 TI - Wild Rabbit Host and Some Parasites Show Trophic-Level Relationships for delta(13)C and delta(15)N: A First Report. AB - Abstract We report the first isotopic study of an animal host-parasite system. Parasitic, intestinal nematodes, Graphidium strigosum and Passalurus ambiguus, were (15)N-enriched relative to their host, the European rabbit Oryctolagus cuniculus, while parasitic cestodes, Cittataenia denticulata and Mosgovoyia pectinata, were (15)N-depleted, suggesting different trophic relationships. Host embryos were more similar in their delta(13)C and delta(15)N values to maternal muscle than were any of the parasites. Coprophagy, the direct recycling of food by the rabbit eating its own faeces, did not lead to isotopic differences between stomach contents and faeces, suggesting that the major point for isotopic discrimination in lagomorph nitrogen metabolism is in the animal rather than in the gut. We conclude that bulk delta(13)C and delta(15)N can reveal valuable new information about host-parasite relationships, and these could be explored further at the biochemical level using compound-specific isotopic analyses. PMID- 22087486 TI - Amino Acid (15)n/(14)n analysis at natural abundances: a new tool for soil organic matter studies in agricultural systems. AB - Abstract The effects of landuse, fertilizer history and soil type on the quantity and isotopic quality of hydrolysable soil amino acids were examined in 3 grassland and 2 arable soils. Results showed, (i) that overall concentrations of individual amino acids were highest in the grassland soils, (ii) that 0/00delta(15)N values of the individual amino acids differed considerably between the five soils, and (iii) that the combination of amino acid 0/00delta(15)N values and concentrations could be used to distinguish between landuse, crop type and fertilizer history. This preliminary study indicates that the pathways of transformation of soil amino acid N are influenced by long term N inputs and that associated biological processes are reflected in differences in concentrations and 0/00delta(15)N values of individual soil amino acids. PMID- 22087488 TI - Estimation of urea production rate with [(15)n(2)]urea and [(13)c]urea to measure catabolic rates in diabetes mellitus. AB - Abstract For verifying catabolic states in insulin-dependent patients and dogs the method estimating urea production rates with (13)C and with doubly (15)N labeled urea, respectively, has been established. For a fast steady state of urea tracer dilution, a prime of 600 times the continuous infusion rate had to be injected. Urea was isolated from plasma samples by protein precipitation and cation exchange chromatography with a consecutive derivatization of the dried urea fraction (trimethylsilyl derivatives). The masses of the fragment ions m/z 189 ((14)N(14)N), 190 ((14)N(15)N) and 191 ((15)N(15)N) urea are monitored to estimate the [(15)N(2)]urea frequency in the overall body urea pool in mol percent excess (MPE). 1 to 15 ng of derivatized urea were measured efficiently. An excellent correlation between expected standard and measured MPE (r = 0.9977) was achieved from solutions containing 1 to 7% [(15)N(2)]urea. The interassay coefficient of variation amounted to < 10% for a [(15)N(2)]urea portion of >= 3%. Normoglycemic diabetic patients who were treated with insulin overnight showed significantly higher urea production compared to healthy controls (9.22 +/- 2.07 vs. 5.4 +/- 0.32 MUmol.kg(-1) . min(-1); p < 0.05). Measurements in chronic diabetic dogs proved an increased rate of amino acid catabolism (+ 20% urea production) in systemic versus portal application of insulin in paired studies. This increased nitrogen load in diabetics may accelerate progression of diabetic nephropathy. - Thus, the established stable isotope technique may serve as a sensitive and useful indicator of amino acid catabolism in clinical and experimental research. PMID- 22087489 TI - Labelling studies for structure elucidation of a new hydroxymetabolite of tramadol. AB - Abstract Tramadol, racemic 1-(3-methoxyphenyl)-2 (dimethylaminomethyl)cyclohexane-1-ol, is an effective analgesic drug. Metabolites of tramadol described so far originate from O- and N-demethylation and are excreted in urine directly or after conjugation. A further metabolite was found in human liver microsome incubations and in the urine of volunteers after ingestion of tramadol. To elucidate the structure of the new metabolite, seven deuterated isotopomers of tramadol have been synthesized and ingested by volunteers. The mass spectra of the metabolites derived showed (i) that it was a hydroxy metabolite, (ii) that the hydroxy group was not located on the aromatic ring, the side chain, or the positions 2 and 6 of the cyclohexane ring, (iii) that the hydroxy-group was introduced to one of the the positions 3, 4 or 5 of the cyclohexane ring. The hydroxy metabolite was formed preferentially from the ( )-enantiomer, (1S,2S)-tramadol. PMID- 22087490 TI - Whole body protein metabolism estimated by (15)n tracer experiments and body composition of mice selected for different growth parameters. AB - Abstract Whole body protein synthesis was investigated in growing male mice which were long-time selected for high carcass protein amount (DU-6P, protein line) or for high body weight (DU-6, growth line) and in the unselected randomly bred control (DU-Ks). Six mice/line were housed singly in metabolic cages for the estimation of N balance, whole body protein synthesis (end-product method, single dose of (15)N-labelled amino-acid mixture), and N distribution in the body. Another six mice/line were used for the determination of the body composition. All mice had free access to a commercial stock diet (crude protein 268 g, gross energy 19 MJ/kg dry matter) and to water. Body weight of both selection lines was about twice that of control mice at the same age. Selection for high body weight resulted in higher body fat content. Scaled to the corresponding body protein pools, the protein synthesis rates of selected mice were significantly higher than in controls, but were not significantly different between both selection lines in contrast to the protein deposition rates. The higher protein accretion in the protein line in comparison to the growth line seems to be due to a combination of a lower protein breakdown and an increased protein synthesis rate. PMID- 22087491 TI - Significance of diagnostic parameters in [(13)c]octanoic Acid gastric emptying breath tests*. AB - Abstract Two novel characteristic parameters, the latency time (t (lat)) and the ascension time (t (asc)), are proposed for evaluation of non-invasive [(13)C]octanoic acid breath tests for assessment of the gastric emptying of solids. In breath tests performed in control subjects (n = 30) and diabetic patients (n = 100), the usefulness of these parameters was compared to conventional parameters, i.e., gastric half emptying-time t (1/2,b )) and lag phase (t (lag,b )). The proposed parameters were only loosely correlated (controls, r = 0.199; diabetics, 0.616). A strong correlation was found between the conventional parameters (controls, r = 0.891; diabetics, r = 0.962). Based on the conventional method, 36 patients were suspicious of delayed gastric emptying including 24 patients which exhibited a simultaneous delay in both parameters. Using the new parameters, a total of 46 patients were suspicious of delayed gastric emptying with 15 and 20 having isolated delay in t (lat) and t (asc), respectively. We conclude that the novel parameters may be more appropriate for examination of the different phases of gastric emptying and for evaluation of gastric emptying disturbances in diabetic patients than the parameters conventionally used for this purpose. PMID- 22087493 TI - Saisonale Variation von Deuterium und Sauerstoff-18 in Luftfeuchte und Niederschlag uber Antarktika. AB - Abstract D and (18)O distributions were investigated in Antarctic precipitation (falling snow) and in water vapour to study their dependance on season and sampling site. Long-term sampling at the former German Georg Forster Station during 1978-93 and at the Japanese Syowa Station during 1994-97 allow conclusions about the present seasonal isotopic variations in the water inflow to Antarctica. The deltaD and delta(18)O values of precipitation at these East Antarctic coastal stations were compared with corresponding data from the West Antarctic Georg von Neumayer and Halley stations. The monthly means of these long-term data sets show typical hysteresis-like seasonal patterns of isotopic composition. Significant time lags exist regarding station temperatures, while water vapour deltaD values do not show such hysteresis patterns. Here, half-yearly and even quarter-yearly time components were found by Fourier analysis. Attempts were made to describe the variation in deltaD and delta(18)O values of water vapour and precipitation as well as in the resulting deuterium excess by the mixed cloud isotopic model (MCIM) of Ciais and Jouzel. PMID- 22087494 TI - Isotope-geochemical and mineralogical-petrographic characteristics of the pergamon altar marble. AB - Abstract We report preliminary results of our provenance study of marble from the Telephos Frieze of the Pergamon altar. The emphasis here is on the stable isotope geochemistry of marble. The obtained delta(13)C values (2.4 to 3.50/00) vary insignificantly. However, the delta(18)O values give two clusters. The isotopically light marbles (close to -9.50/00) derive from panels 1-8 and the heavy marbles (-3.5 to -1.00/00) derive from panels 11-50. Mineralogical, petrographic and geochemical investigations (accessory minerals, grain size distribution, rare earth elements) further refined the marble characteristics. In spite of certain differences observed (grain size distributions, isotopy and contents of certain elements) for the two marble groups, the present data support a common provenance. So far, east Aegean islands and the Marmara region are favored. PMID- 22087495 TI - Methane-derived carbonates in a native sulfur deposit: stable isotope and trace element discriminations related to the transformation of aragonite to calcite. AB - Abstract Stable isotope ((13)C, (18)O, (34)S) and trace element (Sr(2+), Mg(2+), Mn(2+), Ba(2+), Na(+)) investigations of elemental sulfur, primary calcites and mixtures of aragonite with secondary, post-aragonitic calcite from sulfur-bearing limestones have provided new insights into the geochemistry of the mineral forming environment of the native sulfur deposit at Machow (SE-Poland). The carbon isotopic composition of carbonates (delta(13)C = -41 to -470/00 vs. PDB) associated with native sulfur (delta(34)S = + 10 to + 150/00 vs. V-CDT) relates their formation to the microbiological anaerobic oxidation of methane and the reduction of sulfate derived from Miocene gypsum. From a comparison with experimentally derived fractionation factors the element ratios of the aqueous fluids responsible for carbonate formation are estimated. In agreement with field and laboratory observations, ratios near seawater composition are obtained for primary aragonite, whereas the fluids were relatively enriched in dissolved calcium during the formation of primary and secondary calcites. Based on the oxygen isotope composition of the carbonates (delta(18)O = -3.9 to -5.90/00 vs. PDB) and a secondary SrSO(4) (delta(18)O = + 200/00 vs. SMOW; delta(34)S = + 590/00 vs. V-CDT), maximum formation temperatures of 35 degrees C (carbonates) and 47 degrees C (celestite) are obtained, in agreement with estimates for West Ukraine sulfur ores. The sulfur isotopic composition of elemental sulfur associated with carbonates points to intense microbial reduction of sulfate derived from Miocene gypsum (delta(34)S ~ + 230/00) prior to the re-oxidation of dissolved reduced sulfur species. PMID- 22087496 TI - Variations of delta(15)N-Values and Hydrolyzable Amino Acids in Settling Particles in the Ocean. AB - Abstract The modification of nitrogen isotopic signals during particle sedimentation in the sea is of great interest for the use of sedimentary delta(15)N-values as a paleoceanographic tool. The effect of organic matter degradation on such modification was studied by analyzing nitrogen, hydrolyzable amino acids (THAA) and delta(15)N-values in a suit of marine settling particles collected from the Bay of Bengal, Indian Ocean, by using time-series sediment traps, and in underlying sediments. The flux of settling particles showed temporal variations which are related to the monsoons, the major climatic feature of this marine region. During high flux periods settling particles are enriched in nitrogenous material that is less degraded and exhibit higher delta(15)N values than particles showing characteristics of degradation. At the sediment surface more than 95% of the settling particulate nitrogen is lost and the delta(15)N-values of the residual sedimentary nitrogen are higher than those of settling particles. The observed increase is interpreted to be due to fractionation during degradation of organic matter. PMID- 22087501 TI - Editorial board page for "Isotopes in Environmental and Health Studies", Volume 33, Number 1-2. AB - Abstract This is a scanned image of the original Editorial Board page(s) for this issue. PMID- 22087498 TI - Determination of (13)CO(2)/(12)CO(2) Ratio by IRMS and NDIRS. AB - Abstract Breath tests using (13)C-labelled substrates require the measurement of (13)CO(2)/(12)CO(2) ratio in breath gas samples. Next to isotope ratio mass spectrometry (IRMS), which is very sensitive but also complex and expensive, alternatively isotope selective nondispersive infrared spectrometry (NDIRS) can be used to determine the (13)CO(2)/(12)CO(2) ratio in expired breath. In this study we compared NDIRS- with IRMS-results to investigate whether the less expensive and very simply to operate NDIRS works as reliable as IRMS. For this purpose we applicated 1-(13)C-Phenylalanine to patients with advanced liver cirrhosis and healthy volunteers and took duplicated breath samples for IRMS and NDIRS at selected time points. Our data show a good correlation between these two methods for a small number of samples as required for simple breath tests. Longer series, where repeated measurements are required on the NDIRS instrument lead to a decreasing correlation. This indicates the superiority of IRMS concerning (13)CO(2)-kinetics over longer time periods. PMID- 22087502 TI - Relating rates of catalyst sintering to the disappearance of individual nanoparticles during Ostwald ripening. AB - Sintering of nanoparticles (NPs) of Ni supported on MgAl(2)O(4) was monitored in situ using transmission electron microscopy (TEM) during exposure to an equimolar mixture of H(2) and H(2)O at a pressure of 3.6 mbar at 750 degrees C, conditions relevant to methane steam reforming. The TEM images revealed an increase in the mean particle size due to disappearance of smaller, immobile NPs and the resultant growth of the larger NPs. A new approach for predicting the long-term sintering of NPs is presented wherein microscopic observations of the ripening of individual NPs (over a span of a few seconds) are used to extract energetic parameters that allow a description of the collective behavior of the entire population of NPs (over several tens of minutes). PMID- 22087503 TI - Use of non-parametric item response theory to develop a shortened version of the Positive and Negative Syndrome Scale (PANSS). AB - BACKGROUND: Nonparametric item response theory (IRT) was used to examine (a) the performance of the 30 Positive and Negative Syndrome Scale (PANSS) items and their options ((levels of severity), (b) the effectiveness of various subscales to discriminate among differences in symptom severity, and (c) the development of an abbreviated PANSS (Mini-PANSS) based on IRT and a method to link scores to the original PANSS. METHODS: Baseline PANSS scores from 7,187 patients with Schizophrenia or Schizoaffective disorder who were enrolled between 1995 and 2005 in psychopharmacology trials were obtained. Option characteristic curves (OCCs) and Item Characteristic Curves (ICCs) were constructed to examine the probability of rating each of seven options within each of 30 PANSS items as a function of subscale severity, and summed-score linking was applied to items selected for the Mini-PANSS. RESULTS: The majority of items forming the Positive and Negative subscales (i.e. 19 items) performed very well and discriminate better along symptom severity compared to the General Psychopathology subscale. Six of the seven Positive Symptom items, six of the seven Negative Symptom items, and seven out of the 16 General Psychopathology items were retained for inclusion in the Mini-PANSS. Summed score linking and linear interpolation was able to produce a translation table for comparing total subscale scores of the Mini-PANSS to total subscale scores on the original PANSS. Results show scores on the subscales of the Mini-PANSS can be linked to scores on the original PANSS subscales, with very little bias. CONCLUSIONS: The study demonstrated the utility of non-parametric IRT in examining the item properties of the PANSS and to allow selection of items for an abbreviated PANSS scale. The comparisons between the 30-item PANSS and the Mini-PANSS revealed that the shorter version is comparable to the 30-item PANSS, but when applying IRT, the Mini-PANSS is also a good indicator of illness severity. PMID- 22087504 TI - Vascular measures to detect earlier macrovascular disease. PMID- 22087505 TI - Nonsingular adsorption/desorption of chlorpyrifos in soils and sediments: experimental results and modeling. AB - At environmentally relevant concentrations in soils and sediments, chlorpyrifos, a hydrophobic organic insecticide, showed strong adsorption that correlated significantly with organic matter content. Chlorpyrifos desorption followed a nonsingular falling desorption isotherm that was estimated using a memory dependent mathematical model. Desorption of chlorpyrifos was biphasic in nature, with a labile and nonlabile component. The labile component comprised 18-28% of the original solid-phase concentration, and the residue was predicted to slowly partition to the aqueous phase, implying long-term desorption from contaminated soils or sediments. The newly proposed mechanism to explain sorption/desorption hysteresis and biphasic desorption is the unfavorable thermodynamic energy landscape arising from limitation of diffusivity of water molecules through the strongly hydrophobic domain of soils and sediments. Modeling results suggest that contaminated soils and sediments could be secondary long-term sources of pollution. Long-term desorption may explain the detection of chlorpyrifos and other hydrophobic organic compounds in aquatic systems far from application sites, an observation that contradicts conventional transport predictions. PMID- 22087506 TI - Combining indoor residual spraying with chlorfenapyr and long-lasting insecticidal bed nets for improved control of pyrethroid-resistant Anopheles gambiae: an experimental hut trial in Benin. AB - BACKGROUND: Neither indoor residual spraying (IRS) nor long-lasting insecticidal nets (LLINs) are able to fully interrupt transmission in holoendemic Africa as single interventions. The combining of IRS and LLINs presents an opportunity for improved control and management of pyrethroid resistance through the simultaneous presentation of unrelated insecticides. METHOD: Chlorfenapyr IRS and a pyrethroid impregnated polyester LLIN (WHO approved) were tested separately and together in experimental huts in southern Benin against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus. The bed nets were deliberately holed with either six or 80 holes to examine the effect of increasing wear and tear on protectiveness. Anopheles gambiae were genotyped for the kdr gene to assess the combination's potential to prevent the selection of pyrethroid resistance. RESULTS: The frequency of kdr was 84%. The overall mortality rates of An. gambiae were 37% and 49% with the six-hole and 80-hole LLINs, respectively, and reached 57% with chlorfenapyr IRS. Overall mortality rates were significantly higher with the combination treatments (82-83%) than with the LLIN or IRS individual treatments. Blood feeding (mosquito biting) rates were lowest with the 6-hole LLIN (12%), intermediate with the 80-hole LLIN (32%) and highest with untreated nets (56% with the 6-hole and 54% with the 80-hole nets). Blood feeding (biting) rates and repellency of mosquitoes with the combination of LLIN and chlorfenapyr IRS showed significant improvement compared to the IRS treatment but did not differ from the LLIN treatments indicating that the LLINs were the primary agents of personal protection. The combination killed significantly higher proportions of Cx. quinquefasciatus (51%, 41%) than the LLIN (15%, 13%) or IRS (32%) treatments. CONCLUSION: The chlorfenapyr IRS component was largely responsible for controlling pyrethroid-resistant mosquitoes and the LLIN component was largely responsible for blood feeding inhibition and personal protection. Together, the combination shows potential to provide additional levels of transmission control and personal protection against pyrethroid-resistant mosquitoes, thereby justifying the additional resources required. Chlorfenapyr has potential to manage pyrethroid resistance in the context of an expanding LLIN/IRS strategy. PMID- 22087507 TI - Miscibility behavior and nanostructure of monolayers of the main phospholipids of Escherichia coli inner membrane. AB - We report a thermodynamic study of the effect of calcium on the mixing properties at the air-water interface of two phospholipids that mimic the inner membrane of Escherichia coli: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine and 1 palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol. In this study, pure POPE and POPG monolayers and three mixed monolayers, chi(POPE) = 0.25, 0.5, and 0.75, were analyzed. We show that for chi(POPE) = 0.75, the values of the Gibbs energy of mixing were negative, which implies attractive interactions. We used atomic force microscopy to study the structural properties of Langmuir-Blodgett monolayers that were transferred onto mica substrate at lateral surface pressures of 25 and 30 mN m(-1). The topographic images of pure POPE and POPG monolayers exhibited two domains of differing size and morphology, showing a step height difference within the range expected for liquid-condensed and liquid-expanded phases. The images captured for chi(POPE) = 0.25 were featureless, and for chi(POPE) = 0.5 small microdomains were observed. The composition that mimics quantitatively the proportions found in the inner membrane of E. coli , chi(POPE) = 0.75, showed large liquid condensed domains in the liquid expanded phase. The extension of each domain was quantitatively analyzed. Because calcium is used in the formation of supported bilayers of negatively charged phospholipids, the possible influence of the nanostructure of the apical on the distal monolayer is discussed. PMID- 22087508 TI - The National Agricultural Laboratories of Brazil and the control of residues and contaminants in food. AB - The laboratory activity of the Ministry of Agriculture, Livestock and Food Supply in Brazil has a history that is richer than most people are aware of. The institutions that today are known as National Agricultural Laboratory - Lanagros were once a smaller initiative that suffered ups and downs throughout the decades. The recognition that the Lanagros have today - as reference centres with open communication channels with some of the world's greater laboratories in residue and contaminants in food analyses - is the fruit of several years of hard work, good ideas and a strong will never to let down society. Today the Lanagros act not only by performing analyses for the monitoring and investigation programmes, but also in the research and development of analytical methods, providing technical advice on the elaboration of guidelines and normatives, international negotiation and the evaluation of other laboratories. The Lanagros work in an ISO 17025 environment, and they are now being directed and prepared to be able to respond to outbreaks and crises related to the presence of residues and contaminants in food, with the readiness, quickness and reliability that an emergency requires. Investments are allocated strategically and have been giving concrete results, all to the benefit of consumers. PMID- 22087509 TI - Mollenyne A, a long-chain chlorodibromohydrin amide from the sponge Spirastrella mollis. AB - The structure of mollenyne A, a cytotoxic nitrogenous halogenated long-chain carboxamide from the sponge Spirastrella mollis, was elucidated by integrated spectroscopic analysis, including CD, and chemical conversion. PMID- 22087510 TI - Francophones living with HIV/AIDS in Ontario: the unknown reality of an invisible cultural minority. AB - A strong body of evidence demonstrates that education, prevention and intervention, in the context of HIV/AIDS, should take ethno-racial diversity into account. The current research focuses on the cultural sensitivity manifested by AIDS service organisation ASO professionals towards Francophone minority persons living with HIV/AIDS Francophone PHAs in the two main urban centres of Ontario: Ottawa and Toronto. More specifically, this qualitative research will describe two different points of view: Francophone PHA service users n=17 and ASO professionals n=12. Data were collected from multiple focus groups and analysed using a phenomenological methodology. The analysis revealed that an important difference exists in the perceptions of language as an integral part of ethno racial diversity. For ASO professionals, language is perceived as a simple tool of communication. For Francophones living with HIV/AIDS, however, language is perceived as a way to convey sensitivity to their cultural reality and a full recognition of their Canadian citizenship. This research showed that cultural sensitivity should include a linguistic aspect when it comes to health-related services, especially in the context of an officially bilingual country. PMID- 22087511 TI - Coincidence of remission of postpartum Graves' disease and use of omega-3 fatty acid supplements. AB - I developed Graves' Disease four months postpartum. After one year on propylthiouracil, I learned that omega-3 fatty acids may reduce inflammation associated with certain autoimmune disorders, although no investigations for thyroiditis have been reported. Within eight weeks of beginning flaxseed oil supplements, TSH levels normalized, but fell somewhat when flaxseed was decreased and PTU discontinued. During another pregnancy, plasma TSH normalized, but was again suppressed by four weeks postpartum, then undetectable by four months. This time, flaxseed supplementation alone coincided with TSH normalization. Omega-3 fatty acids should be investigated as a potential treatment for autoimmune thyroid disease. PMID- 22087512 TI - Exploring the role of social capital in supporting a regional medical education campus. AB - INTRODUCTION: To help address physician shortages in the underserved community of Prince George, Canada, the University of British Columbia (UBC) and various partners created the Northern Medical Program (NMP), a regional distributed site of UBC's medical doctor undergraduate program. Early research on the impacts of the NMP revealed a high degree of social connectedness. The objective of the present study was to explore the role of social capital in supporting the regional training site and the benefits accrued to a broad range of stakeholders and network partners. METHODS: In this qualitative study, 23 semi-structured interviews were conducted with community leaders in 2007. A descriptive content analysis based on analytic induction technique was employed. Carpiano's Bourdieu based framework of 'neighbourhood' social capital was adapted to empirically describe how social capital was produced and mobilized within and among networks during the planning and implementation of the NMP. RESULTS: Results from this study reveal that the operation of social capital and the related concept of social cohesion are multifaceted, and that benefits extend in many directions, resulting in somewhat unanticipated benefits for other key stakeholders and network partners of this medical education program. Participants described four aspects of social capital: (i) social cohesion; (ii) social capital resources; (iii) access to social capital; and (iv) outcomes of social capital. CONCLUSIONS: The findings of this study suggest that the partnerships and networks formed in the NMP planning and implementation phases were the foundation for social capital mobilization. The use of Carpiano's spatially-bounded model of social capital was useful in this context because it permitted the characterization of relations and networks of a tight-knit community body. The students, faculty and administrators of the NMP have benefitted greatly from access to the social capital mobilized to make the NMP operational. Taking account of the dynamic and multifaceted operation of social capital helps one move beyond a view of geographic communities as simply containers or sinks of capital investment, and to appreciate the degree to which they may act as a platform for productive network formation and expansion. PMID- 22087513 TI - The impact of sodium aescinate on acute lung injury induced by oleic acid in rats. AB - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high rates of morbidity and mortality. Currently, several surfactant or anti-inflammatory drugs are under test as treatments for ALI. Sodium aescinate (SA) has been shown to exert anti-inflammatory and antiedematous effects. In the present work, the authors explored the effects of SA and the possible mechanisms of SA action in rats with ALI induced by oleic acid (OA) administration. Eight groups of rats received infusions of normal saline (NS) or OA. Rats exposed to OA were pretreated with 1 mg/kg of SA, or posttreated with SA at low (1 mg/kg), medium (2 mg/kg), or high (6 mg/kg) dose; a positive-control group received methylprednisolone. The pressure of oxygen in arterial blood (P(O(2))) levels, the pulmonary wet/dry weight (W/D) ratios, and indices of quantitative assessment (IQA) of histological lung injury were obtained 2 or 6 hours after OA injection (0.1 mL/kg, intravenously). The levels of superoxide dismutase (SOD), malondialdehyde (MDA), matrix metalloproteinase gelatinase B (MMP-9), and tissue inhibitor of metalloproteinase (TIMP-1) in both plasma and lung tissue were also determined. Both pre- and posttreatment with SA improved OA induced pulmonary injury, increased P(O(2)) and SOD values, lowered IQA scores, and decreased the lung W/D ratio and MDA and MMP-9 levels in plasma and lung tissue. SA appeared to abrogate OA-induced ALI by modulating the levels of SOD, MDA, and MMP-9 in plasma and lung tissue. PMID- 22087514 TI - The antifibrosis effect of adrenomedullin in human lung fibroblasts. AB - Adrenomedullin (AM) is a regulatory peptide involved in cellular proliferation and protein synthesis. The authors investigated AM and the AM receptor system in the human fetal lung fibroblasts (HFLFs), and assessed whether AM can inhibit proliferation and collagen synthesis in HFLFs under hypoxia. Fibroblasts were exposed to hypoxia (2% O(2)) after the addition of AM. The effects of AM and transforming growth factor beta1 (TGF-beta1) on the proliferation of fibroblasts were determined by the methanethiosulfonate (MTS) assay. Total collagen synthesis was determined by [(3)H]proline incorporation. TGF-beta1 levels in the culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of intracellular calciumion ([Ca(2+)](i)) in fibroblasts was detected with a laser scanning confocal microscope. AM, adrenomedullin receptor (ADMR), calcitonin receptor-like receptor (CRLR), AM receptor chaperone receptor activity-modifying protein-1 (RAMP1),RAMP2, and RAMP3 were detected in the HFLFs. The hypoxia-induced increases in cell proliferation, collagen synthesis, and TGF beta1 production were inhibited by AM. AM also inhibited proliferation and collagen synthesis in fibroblasts induced by TGF-beta1. AM caused a decrease of the hypoxia-induced [Ca(2+)](i) in fibroblasts. This study suggests that AM is produced by HFLFs and AM may function as an antifibrosis factor that protects cells from hypoxic pulmonary damage through its receptors. PMID- 22087515 TI - Preoperative versus postoperative initiation of thromboprophylaxis following major orthopedic surgery: safety and efficacy of postoperative administration supported by recent trials of new oral anticoagulants. AB - In European countries, low-molecular-weight heparin is generally initiated preoperatively for thromboprophylaxis in hip or knee replacement surgery. The objective of this review is to compare pre- and postoperative thromboprophylaxis strategies using available evidence, and discuss the challenges and issues that arise. Surgery is the first step in the process of thrombus formation, but thrombosis is not an instant process and the formation and growth of the thrombus can take several days or weeks. Hence, it may be possible to stop this process if thromboprophylaxis is initiated after surgery. Meta-analyses or systematic reviews comparing pre- and postoperative initiation of therapy have found no consistent differences in efficacy and similar safety (bleeding rates) between the two strategies. The recently available oral anticoagulant dabigatran etexilate provides thromboprophylaxis when administered postoperatively and is as safe as preoperative enoxaparin. Further support for the use of postoperative oral thromboprophylaxis in hip or knee replacement surgery has been provided by the phase III clinical trials of rivaroxaban and apixaban versus preoperative enoxaparin. Postoperative thromboprophylaxis offers the opportunity to change management practices in Europe. As postoperative initiation may have a clinical benefit in some settings (e.g. for neuraxial anesthesia) and practical advantages (e.g. allowing same-day admission), it is a worthwhile thromboprophylactic strategy for hip or knee replacement surgery. PMID- 22087516 TI - Comparative evaluation of IS6110 PCR via conventional methods in rapid diagnosis of new and previously treated cases of extrapulmonary tuberculosis. AB - In developing countries the diagnosis of extrapulmonary tuberculosis (EPTB) is a major burning challenge. EPTB encounters many problems like pauci-bacillary nature, inadequate specimen volume. All the limitations reflect in the poor contribution of conventional bacteriological technique in the establishment of diagnosis of EPTB. Nucleic acid amplification methods are rapid and sensitive has modified strategies for the detection of mycobacterial DNA. A fragment of DNA of 123 bp belonging to insertion sequence IS6110 based on specific gene of Mycobacterium tuberculosis complex was amplified by polymerase chain reaction (PCR) for the rapid diagnosis of EPTB. The present study was to comparative evaluation of IS6110 PCR via conventional methods in the rapid diagnosis of new and Previously treated cases of extra pulmonary tuberculosis. Four hundred fifty specimens were collected from suspected cases of EPTB were processed for Mycobacteria by Zeihl Neelson (ZN) staining and BACTEC culture for M. tuberculosis. All the specimens were also processed for IS6110 based PCR amplification with primers targeting 123 bp fragment of insertion element IS6110 of M. tuberculosis complex. We found significant difference was seen in sensitivities of different tests. Of these 450 specimens, 60 (13.4%) were positive for AFB by ZN staining, 202 (45%) for BACTEC culture and IS6110 PCR were positive for M. tuberculosis complex in 283 (63%) specimens (p< 0.05). However, there was no significant difference (p< 0.05) as far as specificity of different tests. We found that IS6110 PCR has higher sensitivity than smear microscopy and BACTEC culture in both cases of new cases as well as in previously treated cases. IS6110 PCR can be highly useful in diagnosis of new and treated cases of EPTB. It may facilitate therapeutic decisions for those with suspected of EPTB. PMID- 22087517 TI - [The effect of acute internal problems for mortality in respiratory intensive care unit patients]. AB - Acute internal problems in the respiratory intensive care unit (ICU) and risk factors affecting mortality in the acute treatment applications were investigated. All patients in 20-bed intensive care unit for chest diseases enrolled to this prospective observational cohort study during 2008. Patients were classified as living in group 1 and deaths in group 2. Demographics and acute internal problems (arrhythmias, acute kidney-liver failure, dopamine, doputamin, perlinganit infusion) were recorded. Multiple regression analysis was performed for factors affecting mortality. There were 603 patients during the study period, group 1, n= 503 (83.4%), group 2, n= 100 (16.6%). Both groups were similar in terms of age and gender. Odds ratio (OR), 95% confidence interval (CI), p value for internal problems of acute risk factors for mortality were found as; septic shock OR: 22.52, CI 8.11-62.57, p< 0.000; need of perlinganit infusion OR: 9.28, CI: 1.61-53.37, p< 0.012; the presence of arrhythmia, OR: 7.81, CI: 3.46-17.65, p< 0.000; acute renal failure, OR: 2.88, CI: 1.24-6.65, p< 0.013 and the need for dopamine OR: 2.83, CI: 1.06-7.65, p< 0.037, respectively. Internal problems such as cardiac and renal dysfunction can devolop in respiratory ICU patients with pulmonary diseases and these problems constitude additional risk factors for mortalitiy. While the number of ICU is increasing with new health policies, each internal requirement and personnel equipped to treat the problem quickly must be considered. PMID- 22087518 TI - The prevalence of occupational asthma among denim bleachery workers in Kayseri. AB - The bleachery procedure is the most frequent method used to decolorize denims since sandblasting has been shown to cause silicosis. The aim of this study was to determined the prevalence of occupational asthma among denim bleachery workers in Kayseri. The study was conducted in 4 factories, in which jean bleachery was performed, in Kayseri between December 2008 and February 2009. Overall, forty four subjects, 22 from the bleachery section and 22 from the other sections, were included. A questionnaire about respiratory symptoms was administered. Pulmonary function tests (PFTs) and serial peak expiratory flow (PEF) measurements were performed. All subjects were evaluated by posteroanterior chest x-rays. The prevalence of occupational asthma (OA) in the bleachery and other section workers was 23.8% and 9.1%, respectively (p> 0.05). Within workers, exercise dyspnea (23.3%) and wheezing (20.9%) were the most frequent symptoms. The relationship between the duration of employment and PFTs in bleachery workers (n= 21) was negatively correlated and statistically significant with FEV1, FEF25-75 (moderate; r= -0.477, -0.449, respectively; p< 0.05) and FEV1/FVC, FEV1% (well; r= -0.588, -0.509, respectively; p< 0.05). The results of the present study suggest that exposure to denim-bleaching agents plays an important role in the occurrence of respiratory symptoms, reduction in pulmonary functions, and induction of occupational asthma. PMID- 22087519 TI - Reliability and validity of the Turkish version of the pediatric sleep questionnaire: a tool for prediction of sleep related breathing disorder. AB - Use of a questionnaire that predicts the diagnosis and influence of sleep related breathing disorder (SRBD) may be a cost-effective method to aid in both diagnostic algorithm and therapy. Therefore, the aim of this study was to adapt Pediatric Sleep Questionnaire (PSQ) into Turkish and to test the validity and reliability of the Turkish questionnaire. Total of 111 children (59 male, 52 female) aged 2 to 17 years who had symptoms suggestive of SRBD were enrolled consecutively. Demographic characteristics such as age and gender of all children enrolled in the study were recorded. All parents were questioned about symptom severity, frequency and duration. Lastly, PSQ was administered to all parents. Mean age of the children enrolled in the study was 8.1 +/- 3.4 years. Total PSQ score ranged between 0 and 0.95 and mean score was 0.35 +/- 0.22. Comparison of total PSQ scores between children reporting different symptom frequencies demonstrated that PSQ score increased as the symptom frequency increased (p< 0.001). There was a significant difference of all PSQ scores among the groups (p< 0.05 for all). Total PSQ score for children that did not report snoring was 0.2 +/- 0.5 wile that for the ones who snore throughout sleep was 3.8 +/- 0.5 (p< 0.001). Cronbach's alpha values for all domains of PSQ were satisfactory. All items were significantly correlated with their corresponding scale. Turkish version of PSQ is a valid and reliable tool that may be used in the initial evaluation of Turkish children with symptoms suggestive of SRBD. PMID- 22087520 TI - Evaluation of diagnostic accuracy of computed tomography to assess the angioarchitecture of pulmonary sequestration. AB - Bronchopulmonary sequestration is an unusual congenital malformation consisting of abnormal lung tissue that lacks normal communication with the tracheobronchial tree. The diagnosis of pulmonary sequestration is based on identifying this systemic arterial supply. We aimed to evaluate the sensitivity of multidetector computed tomography in demonstrating the feeding artery and draining veins. Between 2003 and 2008, 8 patients (6 males, 2 females) ranging in age from 5 to 49 years with a diagnosis of pulmonary sequestration were identified. All patients underwent evaluation with chest tomography (spiral or multi detector tomography) and digital subtraction angiography. Aberrant systemic arterial supply was demonstrated in all cases: from the descending thoracic aorta (n= 6); arcus aorta (n= 1), internal mammarial artery (n= 1), intercostal arteries (n= 2) and celiac axis (n= 1). Four patients underwent surgery which confirmed the angioarchitecture depicted on angiography. One patient underwent angiography with embolization using. Computed tomography especially multidetector computed tomography is a powerful noninvasive technique for the detection of pulmonary sequestration. PMID- 22087521 TI - Clinical presentations and diagnostic work-up in sarcoidosis: a series of Turkish cases (clinics and diagnosis of sarcoidosis). AB - Sarcoidosis is an idiopathic granulomatous disease. It usually affects the lung. The diagnosis may be problematic since the known causes of granulomatous inflammation must be excluded. This multicenter study aimed to evaluate the clinical presentations and diagnostic approaches of sarcoidosis. The study protocol was sent via internet, and the participants were asked to send the information (clinical, radiological and diagnostic) on newly diagnosed sarcoidosis cases. 293 patients were enrolled within two years. Pulmonary symptoms were found in 73.3% of the patients, and cough was the most common one (53.2%), followed by dyspnea (40.3%). Constitutional symptoms were occured in half of the patients. The most common one was fatigue (38.6%). The most common physical sign was eritema nodosum (17.1%). The most common chest radiograhical sign was bilateral hilar lymphadenomegaly (78.8%). Staging according to chest X ray has revealed that most of the patients were in Stage I and Stage II (51.9% and 31.7%, respectively). Sarcoidosis was confirmed histopathologically in 265 (90.4%) patients. Although one-third of the bronchoscopy was revealed normal, mucosal hyperemi (19.8%) and external compression of the bronchial wall (16.8%) were common abnormal findings. The 100% success rate was obtained in mediastinoscopy among the frequently used sampling methods. Transbronchial biopsy was the most frequently used method with 48.8% success rate. Considering sarcoidosis with its most common and also rare findings in the differential diagnosis, organizing the related procedures according to the possibly effected areas, and the expertise of the team would favour multimodality diagnosis. PMID- 22087522 TI - [Varicella pneumonia requiring invasive mechanical ventilation]. AB - We aimed to report a case of varicella pneumonia that resulted in respiratory failure requiring mechanical ventilation. The patient was a 40-year-old man whose rashes started after his childeren developed varicella and who had a high fever, sputum and sputum with blood, cough, cold and shiver four days before admission. A treatment was commenced by an antiviral acyclovir and ampiric ampicillin sulbactam therapy. Although a supporting oxygen treatment, the patient whose oxygen saturation did not increase and respiratory rate was high was commenced by an invasive mechanical ventilation because of a respiratory failure. The patient that had a recovery in clinical symptoms after 36 hours was extubated and was discharged from hospital by the following week. PMID- 22087523 TI - Giant mediastinal parathyroid adenoma. AB - Primary hyperparathyroidism is most commonly caused by either a parathyroid adenoma or parathyroid hyperplasia. Parathyroid adenomas also rarely attain huge proportions. We present a case of a 63-year-old female patient causing hypercalcemia and the mass which is located in the mediastinum. High intact parathormone level secondary to an ectopic hypersecretory parathyroid adenoma were detected (642 pg/mL). It was removed via a right thoracic approach. In this case parathyroid adenoma measuring 7 x 5 x 4 cm and weighing 145 g; to our knowledge the greatest mass reported in the literature. Despite its huge size it did not cause many of the hypercalcemic symptoms. PMID- 22087524 TI - Bilateral multiple tumor-like endobronchial tuberculosis, diagnosed with bronchoscopic examination. AB - Endobronchial tuberculosis is defined as tuberculosis infection of tracheobronchial tree and it is not seen often in adult population. In the absence of parenchymal disease endobronchial tuberculosis is less well-recognized and can lead to difficulties in diagnosis. Our aim is to introduce a rare form of tuberculosis that is important because of high probability of developing severe bronchostenosis during its course. We report a 20-year-old woman who presented with two-month history of severe non-productive cough, shortness of breath, and hemoptysis. After clinical and radiological evaluation, flexible bronchoscopy showed bilateral multiple tumorous lesions that were seen from main carina down to the both main bronchus. The biopsy samples revealed EBTB diagnosis and antituberculosis therapy was given. At the second month of the therapy, rebronchoscopy revealed almost disappearance of the polypoid lesions. The patient healed without any stenosis. This case report is a reminder that endobronchial tuberculosis must take into consideration in differential diagnosis of endobronchial lesions. In patients with endobronchial tuberculosis healing without any complication could be achieved with timely diagnosis and commencement of early treatment. PMID- 22087525 TI - Recurrent pulmonary tumoral embolism and sudden death as the presenting symptom of Wilms' tumor. AB - Only 4-6% of children with renal tumor show inferior vena caval or right atrial infiltration at presentation. Tumor emboli are even rarer, and so far, sudden death as the presenting symptom has only been described at presentation in Wilms' tumor in eight cases. We report a unique case of Wilms' tumor that presented with small pulmonary emboli and immediately after as that was diagnosed before death by detection of small emboli and immediately after sudden death as massive pulmonary embolism. It seems that in cases of invasive vascular infiltration with a stable hemodynamic condition at diagnosis immediate surgery may be necessary. PMID- 22087526 TI - [Bronchoscopy suite]. AB - Flexible bronchoscopy is usually performed at a tertiary care facility in a general endoscopy unit or a specially designed bronchoscopy suite. The procedure can also be performed outside the designated facility if the qualified personnel and required equipment can be mobilized. In this review, we discuss the essentials of a modern bronchoscopy suite based on the available information from the literature. PMID- 22087527 TI - [A new alternative treatment in COPD: phosphodiesterase-4 inhibitors]. AB - Chronic obstructive pulmonary disease (COPD) is a disease which is characterized with progressive airflow obstruction and abnormal inflammatory response caused by noxious gases and particles. Recently oral phosphodiesterase-4 (PDE-4) inhibitors which block activation of inflammatory cells, are experimented as a new approach. Last studies showed that these drugs improve symptoms, pulmonary functions and quality of life, reduce the numbers of acute attacks, suppress bronchial inflammation in COPD. However these drugs lead to adverse reactions such as vomiting, diarrhea and headache. In this review we discussed roflumilast (Daxas) which was accepted by Food and Drug Administration (FDA), included in treatment of sever COPD in "The Global Initiative for Chronic Obstructive Lung Disease (GOLD)" guideline. PMID- 22087528 TI - Turkish Thoracic Society asthma management and prevention guideline: key points. AB - Asthma still has high morbidity and cost despite all advances in pathogenesis, diagnosis and treatment. Although asthma can be controlled with proper diagnosis and treatment, the low rates of control in our country and in the world can not be attributed to the variable course of the disease and patients' psycho-social behaviours for chronic disease. In this context, Turkish Thoracic Society (TTS) has decided to update Asthma Diagnosis and Management Guide latest published in 2000. National data were collected, compiled and prepared by authors, and final form given by the TTS Asthma and Allergy Study Group, after presenting to consultant individuals and institutions. In June 2009, the National Asthma Management and Prevention Guideline were published in Turkish. In this paper, we aimed to present the national guide in English with its basics and individual differences. PMID- 22087529 TI - Thorax as an extraintestinal target for inflammatory bowel disease. PMID- 22087530 TI - [Bird Breeder's Disease (report of two cases)]. PMID- 22087531 TI - A case of pulmonary embolism confirmed by endobronchial ultrasound. PMID- 22087532 TI - Perceptions of environmental changes and lethargic crab disease among crab harvesters in a Brazilian coastal community. AB - BACKGROUND: Lethargic Crab Disease (LCD) has caused significant mortalities in the population of Ucides cordatus crabs in the Mucuri estuary in Bahia State, Brazil, and has brought social and economic problems to many crab-harvesting communities that depend on this natural resource. The present work examined the perceptions of members of a Brazilian crab harvesting community concerning environmental changes and the Lethargic Crab Disease. METHODS: Field work was undertaken during the period between January and April/2009, with weekly or biweekly field excursions during which open and semi-structured interviews were held with local residents in the municipality of Mucuri, Bahia State, Brazil. A total of 23 individuals were interviewed, all of whom had at least 20 years of crab-collecting experience in the study region. Key-informants (more experienced crab harvesters) were selected among the interviewees using the "native specialist" criterion. RESULTS: According to the collectors, LCD reached the Mucuri mangroves between 2004 and 2005, decimating almost all crab population in the area, and in 2007, 2008 and 2009 high mortalities of U. cordatus were again observed as a result of recurrences of this disease in the region. In addition to LCD, crabs were also suffering great stock reductions due to habitat degradation caused by deforestation, landfills, sewage effluents, domestic and industrial wastes and the introduction of exotic fish in the Mucuri River estuary. The harvesting community was found to have significant ecological knowledge about the functioning of mangrove swamp ecology, the biology of crabs, and the mass mortality that directly affected the economy of this community, and this information was largely in accordance with scientific knowledge. CONCLUSIONS: The study of traditional knowledge makes it possible to better understand human interactions with the environment and aids in the elaboration of appropriate strategies for natural resource conservation. PMID- 22087533 TI - The interaction of bovine serum albumin with doxorubicin-loaded superparamagnetic iron oxide nanoparticles: spectroscope and molecular modelling identification. AB - To take a comprehensive evaluation of the bio-safety of doxorubicin-loaded superparamagnetic iron oxide nanoparticles (SPION), the interaction of bovine serum albumin (BSA) with the drug delivery was investigated by multi spectroscopic techniques and molecular modelling calculation. Ultraviolet absorption and synchronous fluorescence results elucidate that DOX-SPION unfold the framework conformation of BSA, leading to changes in the microenvironment of amide moieties. Circular dichroism (CD) data show that the content of alpha-helix decreases from 68.62% to 62.76%, which shows the changes of protein's secondary structure quantificationally. Through Stern-Volmer analysis, the quenching mode is determined to be static interaction, forming a stable bioconjugate. The molecular model illustrates that DOX prefers a highly polar binding site at the external region of domains ? of BSA, and the hydrogen bonds are marked. This work elucidates that the drug delivery has deleterious effects on the frame conformation of protein, affecting its physiological function. PMID- 22087534 TI - Preparation of a tea polyphenol nanoliposome system and its physicochemical properties. AB - Tea polyphenol is rich in green tea with diverse biological activities. However, its application in the food industry is limited due to its instability toward oxygen and light. In this study, the preparation of tea polyphenol liposome by the thin film ultrasonic dispersion method was performed in order to enhance the bioavailability of tea polyphenol. The process conditions were optimized using response surface analysis, and the optimal parameters were as follows: ratio of tea polyphenol to lecithin, 0.125:1; ratio of lecithin to cholesterol, 4:1; phosphate buffered saline (PBS) pH, 6.62; ultrasonic time, 3.5 min. The theoretical and practical entrapment efficiency were 60.36% and 60.09 +/- 0.69%, respectively. Furthermore, physicochemical properties including size distribution, zeta potential, permeability, infrared spectrum and in vitro release of liposomal formulations were determined. The mean size of tea polyphenol liposome was 160.4 nm, and the zeta-potential value was -67.2. The tea polyphenol liposome was formed by physical interaction, and the in vitro release process followed a first-order equation. The results indicated that the prepared tea polyphenol liposome was stable and suitable for more widespread application. PMID- 22087535 TI - Comparative study of the affinity and metabolism of type I and type II binding quinoline carboxamide analogues by cytochrome P450 3A4. AB - Compounds that coordinate to the heme-iron of cytochrome P450 (CYP) enzymes are assumed to increase metabolic stability. However, recently we observed that the type II binding quinoline carboxamide (QCA) compounds were metabolically less stable. To test if the higher intrinsic clearance of type II binding compounds relative to type I binding compounds is general for other metabolic transformations, we synthesized a library of QCA compounds that could undergo N dealkylation, O-dealkylation, benzylic hydroxylation, and aromatic hydroxylation. The results demonstrated that type II binding QCA analogues were metabolically less stable (2- to 12-fold) at subsaturating concentration compared to type I binding counterparts for all the transformations. When the rates of different metabolic transformations between type I and type II binding compounds were compared, they were found to be in the order of N-demethylation > benzylic hydroxylation> O-demethylation > aromatic hydroxylation. Finally, for the QCA analogues with aza-heteroaromatic rings, we did not detect metabolism in aza aromatic rings (pyridine, pyrazine, pyrimidine), indicating that electronegativity of the nitrogen can change regioselectivity in CYP metabolism. PMID- 22087536 TI - Deactivating chemical agents using enzyme-coated nanofibers formed by electrospinning. AB - The coaxial electrospinning technique was investigated as a novel method to create stabilized, enzyme-containing fibers that have the potential to provide enhanced protection from chemical agents. Electrospinning is a versatile technique for the fabrication of polymer fibers with large length (cm to km): diameter (nm to MUm) aspect ratios. The large surface to volume ratios, along with the biofriendly nature of this technique, enables the fabrication of fiber mats with high enzyme concentrations, which amplify the catalytic activity per unit volume of membrane. Blended composite (single-source) fibers incorporate enzyme throughout the fiber, which may limit substrate accessibility to the enzyme. In contrast, core/sheath fibers can be produced by coaxial electrospinning with very high enzyme loading (>80%) in the sheath without noticeable loss of enzymatic activity. Several core-sheath combinations have been explored with the toxin-mitigating enzyme DFPase in order to achieve fibers with optimum properties. The concentration of fluoride released, normalized for the amount of protein incorporated into the sheath, was used as a measure of the enzyme activity versus time. The coaxial core/sheath combination of PEO and DFPase produced the highest activity (~7.3 mM/mg). PMID- 22087537 TI - Differential glycomics of epithelial membrane glycoproteins from urinary exovesicles reveals shifts toward complex-type N-glycosylation in classical galactosemia. AB - A variety of genetic variations in the galactose-1-phosphate uridyltransferase (GALT) gene cause profound activity loss of the enzyme and acute toxic effects mediated by accumulating metabolic intermediates of galactose in newborns induced by dietary galactose. However, even on a severely galactose-restricted diet, patients develop serious long-term complications of the CNS and ovaries, which may result from damaging perturbations in cell biology caused by endogenously synthezised galactose. Under galactose stress, the cosubstrate of GALT, galactose 1-phosphate, accumulates and disturbs catabolic and anabolic pathways of the carbohydrate metabolism with potential effects on protein glycosylation and membrane localization of glycoprotein receptors, like the epidermal growth factor receptor. To address this issue in view of a cellular pathomechanism, we performed a differential semiquantitative N-glycomics study of membrane proteins. A suitable noninvasive cellular material derived from epithelial plasma membranes was found in urinary exovesicles and in the shed Tamm-Horsfall protein. By applying matrix-assisted laser ionization mass spectrometry on permethylated, PNGaseF released N-glycans, we demonstrate that GALT deficiency is associated with dramatic shifts from prevalent high-mannose-type glycans found in healthy subjects toward complex-type N-linked glycosylation in patients. These N glycosylation shifts were observed on exosomal N-glycoproteins but not on the Tamm-Horsfall glycoprotein, which showed predominant high-mannose-type glycosylation with M6. PMID- 22087538 TI - Expression of ghrelin and its receptors in ovarian endometrioma. AB - Endometriosis is a common gynaecological disorder manifesting by implantation and growth of endometrial tissue outside the uterine cavity. The evidence accumulates that endometriosis may be associated with abrogated regulation of energy balance. Ghrelin is one of the most important orexigenic factor which may also play a role in regulation of inflammatory and angiogenic reactions. The present study was aimed at investigating expression profile of ghrelin and its receptors (GHSR1alpha and GHSR1beta) in endometriotic lesions. The study included ovarian cysts and peritoneal fluid specimens obtained laparoscopically from 20 women with revised American Fertility Society stage III or IV endometriosis. Expression of specific mRNAs was assessed by reverse transcription-polymerase chain reaction. Expression of ghrelin and GHSR1alpha protein was studied by immunohistochemical staining with specific antibodies. Ghrelin and its receptors mRNA expression was found in all tested specimens. Specific mRNAs for these factors were also expressed in the peritoneal leukocytes. Immunohistochemical staining revealed expression of ghrelin and GHSR1alpha both in glandular endometrioid epithelium and in some stromal cells, particularly in some fibroblasts, blood vessels and infiltrating leukocytes. Co-localization of ghrelin and its receptors strongly suggests that this neuropeptide may affect development and growth of endometriotic lesions and may influence local inflammatory and angiogenic response. PMID- 22087539 TI - Methanolysis of thioamide promoted by a simple palladacycle is accelerated by 10(8) over the methoxide-catalyzed reaction. AB - Palladacycle 1 catalyzes the methanolytic cleavage of N-methyl-N-(4 nitrophenyl)thiobenzamide (4) via a mechanism involving formation of a Pd-bound tetrahedral intermediate (TI). The rate constant for decomposition of the complex formed between 1, methoxide, and 4 is 9.3 s(-1) at 25 degrees C; this reaction produces methyl thiobenzoate and N-methyl-4-nitroaniline. The ratio of the second order rate constant for the catalyzed reaction, given as k(cat)/K(d), relative to that of the methoxide-promoted reaction is 3 * 10(8), representing a very large catalysis of thioamide bond cleavage by a synthetic metal complex. PMID- 22087540 TI - Synthesis, absolute configuration, and bacterial mutagenicity of the 8 stereoisomeric vicinal diol epoxides at the terminal benzo ring of carcinogenic dibenz[a,h]anthracene. AB - The synthesis of the 8 possible stereoisomeric diol epoxides (DEs) at the terminal benzo ring of carcinogenic dibenz[a,h]anthracene (DBA) is reported. trans-3,4-Dihydroxy-3,4-dihydro-DBA (1) afforded the 4 bay region DEs: the enantiomeric pairs of the anti diastereomers (+)-3/(-)-3 and of the syn diastereomers (-)-4/(+)-4, respectively. trans-1,2-Dihydroxy-1,2-dihydro-DBA (2) served as precursor of the 4 reverse DEs: the enantiomeric pairs of the anti diastereomers (+)-5/(-)-5 and of the syn diastereomers (-)-6/(+)-6, respectively. The transformation of the olefinic double bond in the enantiomeric trans dihydrodiols to epoxides was achieved by either (i) oxidation with m chloroperoxybenzoic acid or (ii) formation of a bromohydrin with N bromoacetamide/H(2)O followed by dehydrobromination with an anion exchange resin. Because of the pseudodiequatorial conformation of the hydroxyl groups in 1, both reactions proceeded highly stereoselectively, while the stereoselectivity was impaired by the pseudodiaxial conformation of the hydroxyl groups in 2. Diastereomers and racemic compounds were efficiently separated without derivatization by HPLC on achiral or chiral stationary phases, respectively. The absolute configurations of the DEs were deduced from the absolute configuration of 1 and 2 considering the regio- and stereoselectivity of the subsequent reactions and resulted in (+)-(1R,2S,3S,4R)-3/(-)-(1S,2R,3R,4S)-3, (-) (1S,2R,3S,4R)-4/(+)-(1R,2S,3R,4S)-4, (+)-(1R,2S,3S,4R)-5/(-)-(1S,2R,3R,4S)-5, and (-)-(1R,2S,3R,4S)-6/(+)-(1S,2R,3S,4R)-6. The bacterial mutagenicity of the 8 stereoisomeric DEs was determined in histidine-dependent strains TA98 and TA100 of Salmonella typhimurium in the absence of a metabolizing system. In general, the bay region DEs of DBA were stronger mutagens than the reverse DEs. In strain TA98, the syn diastereomers of bay region DEs were stronger mutagens than their anti isomers, while in the case of reverse DEs the anti diastereomers were more potent than their syn isomers. In strain TA100, all syn diastereomers surpassed the bacterial mutagenicity of their anti isomers. Concerning the bay region DEs of DBA, this corresponds to the situation described for benzo[a]pyrene: of the 4 enantiomeric bay region DEs of DBA and benzo[a]pyrene, the syn diastereomer with [(R,S)-diol (R,S)-epoxide] absolute configuration is the most potent mutagen in both bacterial strains, while the anti isomer with [(S,R)-diol (R,S)-epoxide] configuration is the weakest mutagen. PMID- 22087541 TI - Three genetic polymorphisms of homocysteine-metabolizing enzymes and risk of coronary heart disease: appraisal of a recent meta-analysis. PMID- 22087542 TI - Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling. AB - A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. PMID- 22087544 TI - Supported ionic liquid membranes for removal of dioxins from high-temperature vapor streams. AB - Dioxins and dioxin-like chemicals are predominantly produced by thermal processes such as incineration and combustion at concentrations in the range of 10-100 ng of I-TEQ/kg (I-TEQ = international toxic equivalents). In this work, a new approach for the removal of dioxins from high-temperature vapor streams using facilitated supported ionic liquid membranes (SILMs) is proposed. The use of ceramic membranes containing specific ionic liquids, with extremely low volatility, for dioxin removal from incineration sources is proposed owing to their stability at very high temperatures. Supported liquid membranes were prepared by successfully immobilizing the ionic liquids tri-C(8)-C(10) alkylmethylammonium dicyanamide ([Aliquat][DCA]) and 1-n-octyl-3 methylimidazolium dicyanamide ([Omim][DCA]) inside the porous structure of ceramic membranes. The porous inorganic membranes tested were made of titanium oxide (TiO(2)), with a nominal pore size of 30 nm, and aluminum oxide (Al(2)O(3)), with a nominal pore size of 100 nm. The ionic liquids were characterized, and the membrane performance was assessed for the removal of dioxins. Different materials (membrane pore size, type of ionic liquid, and dioxin) and different operating conditions (temperature and flow rate) were tested to evaluate the efficiency of SILMs for dioxin removal. All membranes prepared were stable at temperatures up to 200 degrees C. Experiments with model incineration gas were also carried out, and the results obtained validate the potential of using ceramic membranes with immobilized ionic liquids for the removal of dioxins from high-temperature vapor sources. PMID- 22087543 TI - Undernutrition among HIV-positive children in Dar es Salaam, Tanzania: antiretroviral therapy alone is not enough. AB - BACKGROUND: The prevalence of HIV/AIDS has exacerbated the impact of childhood undernutrition in many developing countries, including Tanzania. Even with the provision of antiretroviral therapy, undernutrition among HIV-positive children remains a serious problem. Most studies to examine risk factors for undernutrition have been limited to the general population and ART-naive HIV positive children, making it difficult to generalize findings to ART-treated HIV positive children. The objectives of this study were thus to compare the proportions of undernutrition among ART-treated HIV-positive and HIV-negative children and to examine factors associated with undernutrition among ART-treated HIV-positive children in Dar es Salaam, Tanzania. METHODS: From September to October 2010, we conducted a cross-sectional survey among 213 ART-treated HIV positive and 202 HIV-negative children in Dar es Salaam, Tanzania. We measured the children's anthropometrics, socio-demographic factors, food security, dietary habits, diarrhea episodes, economic status, and HIV clinical stage. Data were analyzed using both univariate and multivariate methods. RESULTS: ART-treated HIV positive children had higher rates of undernutrition than their HIV-negative counterparts. Among the ART-treated HIV-positive children, 78 (36.6%) were stunted, 47 (22.1%) were underweight, and 29 (13.6%) were wasted. Households of ART-treated HIV-positive children exhibited lower economic status, lower levels of education, and higher percentages of unmarried caregivers with higher unemployment rates. Food insecurity was prevalent in over half of ART-treated HIV positive children's households. Furthermore, ART-treated HIV-positive children were more likely to be orphaned, to be fed less frequently, and to have lower body weight at birth compared to HIV-negative children.In the multivariate analysis, child's HIV-positive status was associated with being underweight (AOR = 4.61, 95% CI 1.38-15.36 P = 0.013) and wasting (AOR = 9.62, 95% CI 1.72-54.02, P = 0.010) but not with stunting (AOR = 0.68, 95% CI 0.26-1.77, P = 0.428). Important factors associated with underweight status among ART-treated HIV positive children included hunger (AOR = 9.90, P = 0.022), feeding frequency (AOR = 0.02, p < 0.001), and low birth weight (AOR = 5.13, P = 0.039). Factors associated with wasting among ART-treated HIV-positive children were diarrhea (AOR = 22.49, P = 0.001) and feeding frequency (AOR = 0.03, p < 0.001). CONCLUSION: HIV/AIDS is associated with an increased burden of child underweight status and wasting, even among ART-treated children, in Dar es Salaam, Tanzania. In addition to increasing coverage of ART among HIV-positive children, interventions to ameliorate poor nutrition status may be necessary in this and similar settings. Such interventions should aim at promoting adequate feeding patterns, as well as preventing and treating diarrhea. PMID- 22087546 TI - Effect of precursor-layer surface charge on the layer-by-layer assembly of polyelectrolyte/nanoparticle multilayers. AB - In this Article, we investigate the effect of a precursor layer, which is composed of four bilayers of polyethyleneimine (PEI) and poly(sodium styrene sulfonate) (PSS), on the subsequent LBL assembly of hybrid films composed of indium tin oxide (ITO) nanoparticles and PSS. A precursor polyelectrolyte layer is usually deposited to minimize interference by the substrate. It is shown here that the "effective" surface charge of the precursor layer can significantly affect the subsequent assembly behavior of [ITO/PSS](9.5) hybrid thin films. Depending on the surface charge of the precursor layer, the subsequent LbL assembly of [ITO/PSS](9.5) hybrid films can exhibit either one or two regimes. When two growth regimes are present, the first one consists of a "recovery regime", and the second is the expected "linear growth regime." The length of the "recovery regime" is dependent on how much positive charge the precursor layer possesses and how fast this surface charge can be compensated. This work reveals for the first time that changes in the surface charge of the precursor layer can have a significant effect on the subsequent LBL assembly process. The surface charge of the precursor layer was investigated using zeta-potential measurements on model silica microspheres. These experiments showed that the surface charge of the precursor layer, [PEI/PSS](4), is dependent on the pH of the solution in which it is immersed, and that it can reverse from a negatively charged surface to a positively charged one, at sufficiently low pH due to the protonation of PEI, despite having the negatively charged PSS layer as the outermost layer. PMID- 22087545 TI - Mediterranean Diet Effect: an Italian picture. AB - BACKGROUND: The purpose of this study was to evaluate the overall diet quality effects, mainly on antioxidant nutritional status and some cytokines related to the cellular immune response as well as oxidative stress in a healthy Italian population group. METHODS: An observational study was conducted on 131 healthy free-living subjects. Dietary intake was assessed by dietary diary. Standardised procedures were used to make anthropometric measurements. On blood samples (serum, plasma and whole blood) were evaluated: antioxidant status by vitamin A, vitamin E, carotenoids, vitamin C, uric acid, SH groups, SOD and GPx activities; lipid blood profile by total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides; total antioxidant capacity by FRAP and TRAP; the immune status by TNF-alpha, and IL-10 cytokines; the levels of malondialdehyde in the erythrocytes as marker of lipid peroxidation. RESULTS: The daily macronutrients intake (g/day) have shown a high lipids consumption and significant differences between the sexes with regard to daily micronutrients intake. On total sample mean Mediterranean Diet Score (MDS) was 4.5 +/- 1.6 and no significant differences between the sexes were present. A greater adherence to a Mediterranean dietary pattern increases the circulating plasma levels of carotenoids (lutein plus zeaxanthin, cryptoxanthin, alpha and beta-carotene), vitamin A and vitamin E. The levels of endogenous antioxidants were also improved. We observed higher levels in anti-inflammatory effect cytokines (IL-10) in subjects with MDS >= 6, by contrast, subjects with MDS <= 3 show higher levels in sense of proinflammatory (TNF alpha P < 0.05). Lower levels of MDA were associated with MDS > 4. Our data suggest a protective role of vitamin A against chronic inflammatory conditions especially in subjects with the highest adherence to the Mediterranean-type dietary pattern. CONCLUSIONS: Mediterranean dietary pattern is associated with significant amelioration of multiple risk factors, including a better cardiovascular risk profile, reduced oxidative stress and modulation of inflammation. PMID- 22087547 TI - A mathematical model of psychotherapy: an investigation using dynamic non-linear equations to model the therapeutic relationship. AB - Mathematical models, such as the one developed by Gottman et al. (1998, 2000, 2002) to understand the interaction between husbands and wives, can provide novel insights into the dynamics of the therapeutic relationship. A set of nonlinear equations were used to model the changing emotional state of a therapist and client. The results suggest: (1) The person that is most responsive to the other achieves the most positive state, (2) the emotional state of the client oscillates before reaching its final state, (3) therapy is least successful when the therapist starts from a negative state, and (4) there is an inverse relationship between models that change only the influence parameter and models that change only the inertia parameter, creating a series of four basic models to work with. These theoretical models require further, empirical investigation to test the derived parameters. If validated, or revised based on observations of therapist-client relationships in development, they could provide specific direction in creating successful therapeutic relationships for training clinicians and those already in practice. PMID- 22087548 TI - Synthesis and fluorescence properties of novel pyrazine-boron complexes bearing a beta-iminoketone ligand. AB - A novel fluorescence dye based on pyrazine-boron complexes bearing a beta iminoketone ligand has been synthesized by using a simple two-step reaction. Synthesized complexes exhibited fluorescence in solution (F(max): 472-604 nm) and in the solid state (F(max): 496-624 nm). These complexes showed a larger Stokes shift (3690-4900 cm(-1)) than well-known boron dipyrromethene dyes (400-600 cm( 1), in most cases). PMID- 22087549 TI - "The group" in integrated HIV and livelihoods programming: opportunity or challenge? AB - HIV care and treatment providers across sub-Saharan Africa are integrating livelihood interventions to improve food security of their clientele. Many integrated HIV and livelihood programmes (IHLPs) require the formation and use of groups of HIV-infected/affected individuals as the operational target for programme interventions, indeed, virtually without exception the group is the focal point for material and intellectual inputs of IHLPs. We sought to critically examine the group approach to programming among IHLPs in Uganda, and to explore and problematise the assumptions underpinning this model. A case study approach to studying 16 IHLPs was adopted. Each IHLP was treated as a case comprising multiple in-depth interviews conducted with staff along the livelihood programme chain. Additionally, in-depth interviews were conducted with staff from The AIDS Support Organization (TASO), and with members of 71 HIV-infected TASO registered client households. Our analysis reveals three important considerations in IHLP programming regarding the group-centred approach: (1) Group membership is widely held to confer benefits in the form of psycho-social and motivational support, particularly in empowering individuals to access HIV services and handle stigma. This is contrasted with the problem of stigma inherent in joining groups defined by HIV-status; (2) Membership in groups can bring economic benefits through the pooling of labour and resources. These benefits however need to be set against the costs of membership, when members are required to make contributions in the form of money, goods or labour; (3) Sharing of goods and labour in the context of group membership allow members to access benefits which would otherwise be inaccessible. In exchange, individual choice and control are diminished and problems of resources held in common can arise. While the group model can bring benefits to IHLP efficiency and by extension to food security, and other outcomes, its application needs to be carefully scrutinised at the individual programme level, in terms of whether it is an appropriate approach, and in terms of mitigating potentially adverse effects. PMID- 22087551 TI - The impact and management of nonmotor symptoms of Parkinson's disease. AB - Parkinson's disease (PD) is a common neurodegenerative disorder diagnosed by the presence of bradykinesia and at least 1 of the symptoms of rigidity, resting tremor, or postural instability. It is increasingly recognized that nonmotor symptoms are common and can adversely affect quality of life, yet they often are not diagnosed and consequently are often untreated. Nonmotor symptoms include neuropsychiatric issues such as anxiety, depression, hallucinations, impulse control disorders, and cognitive impairment, as well as autonomic dysfunction, which may present as gastrointestinal, urinary, and sexual disturbances. Nonmotor symptoms also include excessive sweating, orthostatic hypotension, and sleep disturbances. Management of PD requires recognition of both motor and nonmotor symptoms as well as an understanding of the relationship between these symptoms and how they can be affected by treatments for PD. Therapy should be individualized for each patient, as treatments for the motor symptoms of PD can improve some nonmotor symptoms while they can worsen others. In many cases, symptom-specific treatments are necessary to control nonmotor symptoms of PD. PMID- 22087550 TI - Role of blood cell-associated angiotensin II type 1 receptors in the cerebral microvascular response to ischemic stroke during angiotensin-induced hypertension. AB - BACKGROUND: Angiotensin II type 1 receptor (AT1R) blockers lower the incidence of ischemic stroke in hypertensive patients and attenuate brain inflammation and injury in animal models. Although AT1R on both blood cells (BC) and vascular endothelial cells (EC) can be activated by angiotensin II (Ang II) to elicit inflammation, little is known about the relative contributions of AT1R expressed on BC and EC to the brain injury responses to ischemia and reperfusion (I/R) in the setting of angiotensin-induced hypertension. METHODS: The contributions of BC and EC-associated AT1R to I/R-induced brain inflammation and injury were evaluated using wild type (WT), AT1aR-/-, and bone marrow chimera mice with either a BC+/EC+ (WT->WT) or BC-/EC+ (AT1aR-/-->WT) distribution of AT1aR. The adhesion of leukocytes and platelets in venules, blood brain barrier (BBB) permeability and infarct volume were monitored in postischemic brain of normotensive and Ang II-induced hypertensive mice. RESULTS: The inflammatory (blood cell adhesion) and injury (BBB permeability, infarct volume) responses were greatly exaggerated in the presence of Ang II-induced hypertension. The Ang II-enhanced responses were significantly blunted in AT1aR-/- mice. A similar level of protection was noted in AT1aR-/- ->WT mice for BBB permeability and infarct volume, while less or no protection was evident for leukocyte and platelet adhesion, respectively. CONCLUSIONS: BC- and EC-associated AT1aR are both involved in the brain injury responses to ischemic stroke during Ang II hypertension, with EC AT1aR contributing more to the blood cell recruitment response and BC AT1aR exerting a significant influence on the BBB disruption and tissue necrosis elicited by I/R. PMID- 22087552 TI - Advanced strategies for treatment of Parkinson's disease: the role of early treatment. AB - Parkinson's disease (PD) is associated with significant patient disability and costs to the healthcare system. It is questioned whether early treatment may improve outcomes and delay disability. Early treatment relies on early diagnosis, which can be difficult to achieve because the diagnosis of PD is based on motor symptoms, is clinical in nature, and is complicated by potential presentation of nonmotor symptoms prior to motor symptoms. Economic analyses demonstrate that treatments other than levodopa may be cost-effective. The lack of correlation between Unified PD Rating Scale (UPDRS) outcomes and imaging studies of dopamine uptake may reflect the inappropriate selection of study end points, since activities of daily living scores may be more applicable than motor function scores. Levodopa, the standard therapy for motor control of PD and one of the most effective options, is associated with complications (a wearing-off effect) when used long term. Other therapies, including dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors, may limit the rate of dyskinesia relative to levodopa-based regimens. It appears that early treatment with the MAO-B inhibitor rasagiline (1 mg), as compared with late treatment, delays the onset of worsened UPDRS score, especially the nonmotor activities of daily living subscore. PMID- 22087553 TI - Implications for managed care for improving outcomes in Parkinson's disease: balancing aggressive treatment with appropriate care. AB - Disability in Parkinson's disease (PD) is due not only to progressive impairment in balance, gait, and motor-related tasks, but also to several nonmotor symptoms affecting autonomic, neuropsychiatric, and sensory functions. The prevalence of PD in the United States is rising due to the expanding elderly population. Direct medical costs associated with PD are significant and influenced by level of disability and associated complexity of management. As new treatments are made available, reevaluation of treatment benefits and paradigms is warranted, for both motor and nonmotor symptoms of PD, to better manage outcomes. In addition to evaluation of symptomatic therapies for PD, attention to advances in disease modifying therapies and to management of nonmotor symptoms should be an integral component of PD surveillance in the managed care environment. PMID- 22087554 TI - EscI: a crucial component of the type III secretion system forms the inner rod structure in enteropathogenic Escherichia coli. AB - The T3SS (type III secretion system) is a multi-protein complex that plays a central role in the virulence of many gram-negative bacterial pathogens. This apparatus spans both bacterial membranes and transports virulence factors from the bacterial cytoplasm into eukaryotic host cells. The T3SS exports substrates in a hierarchical and temporal manner. The first secreted substrates are the rod/needle proteins which are incorporated into the T3SS apparatus and are required for the secretion of later substrates, the translocators and effectors. In the present study, we provide evidence that rOrf8/EscI, a poorly characterized locus of enterocyte effacement-encoded protein, functions as the inner rod protein of the T3SS of EPEC (enteropathogenic Escherichia coli). We demonstrate that EscI is essential for type III secretion and is also secreted as an early substrate of the T3SS. We found that EscI interacts with EscU, the integral membrane protein that is linked to substrate specificity switching, implicating EscI in the substrate-switching event. Furthermore, we showed that EscI self associates and interacts with the outer membrane secretin EscC, further supporting its function as an inner rod protein. Overall, the results of the present study suggest that EscI is the YscI/PrgJ/MxiI homologue in the T3SS of attaching and effacing pathogens. PMID- 22087555 TI - Change in self-reported emotional distress and parenting among parents referred to inpatient child psychiatric family treatment. AB - AIMS: Our aim was to examine changes in distress symptoms and parenting dimensions among parents in child psychiatry services (clinic parents) (n = 102). Parents were followed from referral and admission to 3-month and 12-month follow ups of "treatment-as-usual" at inpatient family clinics. These measurements were compared with a sample of community parent (n = 439) standards. METHODS: Standardized questionnaires measuring the child's problems, parental anxiety and depression symptoms (distress), and warmth protectiveness and authoritarianism (parenting dimensions), were distributed to parents four times (T0-T1-T2-T3). The family clinics received families whose children had long-term problems and unsatisfactory previous treatment outcomes. RESULTS: Clinic mothers, but not fathers, showed an improvement in distress symptoms at the 3-month (T2) and 12 month (T3) follow-ups relative to at admission (T1). Nevertheless, clinic mothers displayed distress symptoms at all measurement points compared with community parents. Parents of children with learning/developmental problems and attention disorders showed significantly higher warmth scores at the 3-month and 12-month follow-up compared with at admission, although the levels remained lower than those of community parents. In contrast, parents of children with emotional problems showed the same level of warmth as community parents and lower levels of protectiveness, but no change in these parenting dimensions T1-T2. IMPLICATIONS: Parental emotional distress symptoms and parenting characteristics should be addressed systematically in child psychiatry to inform evaluations of the context of the child's problems and the family's treatment needs. Systematic and effective treatment components related to parenting should be implemented. PMID- 22087556 TI - The influence of environmental factors on the generalisability of public health research evidence: physical activity as a worked example. AB - BACKGROUND: It is rare that decisions about investing in public health interventions in a city, town or other location can be informed by research generated in that specific place. It is therefore necessary to base decisions on evidence generated elsewhere and to make inferences about the extent to which this evidence is generalisable to the place of interest. In this paper we discuss the issues involved in making such inferences, using physical activity as an example. We discuss the ways in which elements of the structural, physical, social and/or cultural environment (environmental factors [EFs]) can shape physical activity (PA) and also how EFs may influence the effectiveness of interventions that aim to promote PA. We then highlight the ways in which EFs may impact on the generalisability of different types of evidence. DISCUSSION: We present a framework for thinking about the influence of EFs when assessing the generalisability of evidence from the location in which the evidence was generated (place A) to the location to which the evidence is to be applied (place B). The framework relates to similarities and differences between place A and place B with respect to: a) the distributions of EFs; b) the causal pathways through which EFs or interventions are thought to exert their effect on PA and c) the ways in which EFs interact with each other. We suggest, using examples, how this scheme can be used by public health professionals who are designing, executing, reporting and synthesising research on PA; or designing/implementing interventions. SUMMARY: Our analysis and scheme, although developed for physical activity, may potentially be adapted and applied to other evidence and interventions which are likely to be sensitive to influence by elements of the structural, physical, social and/or cultural environment such as the epidemiology of obesity and healthy weight promotion. PMID- 22087557 TI - Antiproliferative activity of pomiferin in normal (MCF-10A) and transformed (MCF 7) breast epithelial cells. AB - Pomiferin and osajin are prenylated isoflavones from Osage orange fruit that both have potent antioxidant activity in a variety of assays. Pomiferin, in particular, has strong activity against the superoxide anion in a photochemiluminescence (PCL) assay system. In vitro, pomiferin, but not osajin, demonstrated selective antiproliferative activity against the tumorigenic breast epithelial cell line MCF-7 (IC(50) = 5.2 MUM) with limited toxicity toward nontumorigenic breast epithelial cells (MCF-10A). The differential sensitivity of normal and tumorigenic cells to the antiproliferative action of pomiferin was examined further by using cDNA microarrays. With a stringent cutoff of p < 0.01, a total of 94 genes were significantly differentially expressed between MCF-7 and MCF-10A cells; 80 up-regulated and 14 down-regulated when cells were exposed to 5 MUM pomiferin for 24 h. Fold changes by microarray analysis were confirmed using RT-qPCR, and the most significant changes were found with genes related to antioxidant enzymes. Genes involved in mitotic inhibition and apoptotic regulations were also found to be up-regulated. Pomiferin is therefore a good anticancer candidate agent that may be useful either alone or in combination with other therapeutic agents and, because of its selectivity toward tumor cells, likely to have fewer side effects that classic chemotherapy drugs. PMID- 22087558 TI - Virtual 3D tumor marking-exact intraoperative coordinate mapping improve post operative radiotherapy. AB - The quality of the interdisciplinary interface in oncological treatment between surgery, pathology and radiotherapy is mainly dependent on reliable anatomical three-dimensional (3D) allocation of specimen and their context sensitive interpretation which defines further treatment protocols. Computer-assisted preoperative planning (CAPP) allows for outlining macroscopical tumor size and margins. A new technique facilitates the 3D virtual marking and mapping of frozen sections and resection margins or important surgical intraoperative information. These data could be stored in DICOM format (Digital Imaging and Communication in Medicine) in terms of augmented reality and transferred to communicate patient's specific tumor information (invasion to vessels and nerves, non-resectable tumor) to oncologists, radiotherapists and pathologists. PMID- 22087559 TI - Independent cytotoxic and inflammatory responses to zinc oxide nanoparticles in human monocytes and macrophages. AB - Significant public and scientific concerns remain for the use of nanoparticles (NPs) in commercial products, particularly those applied topically for skin care. There are currently a range of metal oxides formulated into many sunscreens that are present at the nanoscale. In this study, we sought to determine the effect of the size and dispersion of one type of these NPs (zinc oxide) on immune cell function and cytotoxicity for human macrophages and monocytes, which are key cells for particle and debris clearance in the skin. We have found that particle size and coating, but surprisingly, not agglomeration, are key determinates of nanoparticle cytotoxicity in an in vitro culture system of human immune cells. Most importantly, we found that this nanoparticle-induced cellular immune signalling, can be decoupled from cytotoxicity and surface coating, so that at an equivalent cytotoxic load, smaller particles induce a greater cellular response. PMID- 22087560 TI - Evolutionary insights into postembryonic development of adult intestinal stem cells. AB - In the adult vertebrate intestine, multi-potent stem cells continuously generate all of the epithelial cells throughout the adulthood. While it has long been known that the frog intestine is formed via the development of adult intestinal stem cells during thyroid hormone (TH)-dependent metamorphosis, the basic structure of the adult intestine is formed by birth in mammals and it is unclear if the subsequent maturation of the intestine involves any changes in the intestinal stem cells. Two recent papers showing that B lymphocyte-induced maturation protein 1 (Blimp1) regulates postnatal epithelial stem cell reprogramming during mouse intestinal maturation support the model that adult intestinal stem cells are developed during postembryonic development in mammals, in a TH-dependent process similar to intestinal remodeling during amphibian metamorphosis. Since the formation of the adult intestine in both mammals and amphibians is closely associated with the adaptation from aquatic to terrestrial life during the peak of endogenous TH levels, the molecular mechanisms by which the adult stem cells are developed are likely evolutionally conserved. PMID- 22087561 TI - A 3D-QSAR-driven approach to binding mode and affinity prediction. AB - A method for predicting the binding mode of a series of ligands is proposed. The procedure relies on three-dimensional quantitative structure-activity relationships (3D-QSAR) and does not require structural knowledge of the binding site. Candidate alignments are automatically built and ranked according to a consensus scoring function. 3D-QSAR analysis based on the selected binding mode enables affinity prediction of new drug candidates having less than 10 rotatable bonds. PMID- 22087562 TI - Electronic stabilization of trigonal bipyramidal clusters: the role of the Sn(II) ions in [Pt5(CO)5{Cl2Sn(MU-OR)SnCl2}3]3- (R = H, Me, Et, iPr). AB - The new [Pt(5)(CO)(5){Cl(2)Sn(MU-OR)SnCl(2)}(3)](3-) (R = H, Me, Et, (i)Pr; 1-4) clusters contain trigonal bipyramidal (TBP) Pt(5)(CO)(5) cores, as certified by the X-ray structures of [Na(CH(3)CN)(5)][NBu(4)](2)[1].2CH(3)CN and [PPh(4)](3)[4].3CH(3)COCH(3). The TBP geometry, which is rare for group 10 metals, is supported by an unprecedented interpenetration with a nonbonded trigonal prism of tin atoms. By capping all the Pt(3) faces, the Sn(II) lone pairs account for both Sn-Pt and Pt-Pt bonding, as indicated by DFT and topological wave function studies. In the TBP interactions, the metals use their vacant s and p orbitals using the electrons provided by Sn atoms, hence mimicking the electronic picture of main group analogues, which obey the Wade's rule. Other metal TBP clusters with the same total electron count (TEC) of 72 are different because the skeletal bonding is largely contributed by d-d interactions (e.g., [Os(5)(CO)(14)(PR(3))(MU-H)(n)](n-2), n = 0, 1, 2). In 1-4, fully occupied d shells at the Pt(ax) atoms exert a residual nucleophilicity toward the adjacent main group Sn(II) ions permitting their hypervalency through unsual metal donation. PMID- 22087563 TI - Monounsaturated fatty acid, carbohydrate intake, and diabetes status are associated with arterial pulse pressure. AB - BACKGROUND: Diabetes is a global epidemic. Cardiovascular disease (CVD) is one of the most prevalent consequences of diabetes. Nutrition is considered a modifiable risk factor for CVD, particularly for individuals with diabetes; albeit, there is little consensus on the role of carbohydrates, proteins and fats for arterial health for persons with or without diabetes. In this study, we examined the association of macronutrients with arterial pulse pressure (APP), a surrogate measure of arterial health by diabetes status and race. METHODS: Participants were 892 Mexican Americans (MA), 1059 Black, non-Hispanics (BNH) and 2473 White, non-Hispanics (WNH) with and without diabetes of a weighted sample from the National Nutrition and Health Examination Survey (NHANES) 2007-2008. The cross sectional analysis was performed with IBM-SPSS version 18 with the complex sample analysis module. The two-year sample weight for the sub-sample with laboratory values was applied to reduce bias and approximate a nationally, representative sample. Arterial stiffness was assessed by arterial pulse pressure (APP). RESULTS: APP was higher for MA [B = 0.063 (95% CI 0.015 to 0.111), p = 0.013] and BNH [B = 0.044 (95% CI 0.006 to 0.082), p = 0.018] than WNH, controlling for diabetes, age, gender, body mass index (BMI), fiber intake, energy intake (Kcal) and smoking. A two-way interaction of diabetes by carbohydrate intake (grams) was inversely associated with APP [B = -1.18 (95% CI -0.178 to -0.058), p = 0.001], controlling for race, age, gender, BMI, Kcal and smoking. BNH with diabetes who consumed more mono-unsaturated fatty acids (MUFA) than WNH with diabetes had lower APP [B = -0.112 (95%CI-0.179 to -0.045), p = 0.003] adjusting for saturated fatty acids, Kcal, age, gender, BMI and smoking. CONCLUSION: Higher MUFA and carbohydrate intake for persons with diabetes reflecting lower APP may be due to replacement of saturated fats with CHO and MUFA. The associations of APP with diabetes, race and dietary intake need to be confirmed with intervention and prospective studies. Confirmation of these results would suggest that dietary interventions for minorities with diabetes may improve arterial health. PMID- 22087564 TI - Effects of maternal education on diet, anemia, and iron deficiency in Korean school-aged children. AB - BACKGROUND: We investigated the relationship among socioeconomic status factors, the risk of anemia, and iron deficiency among school-aged children in Korea. METHODS: The sample consisted of fourth-grade students aged 10 y recruited from nine elementary schools in Korean urban areas in 2008 (n = 717). Anthropometric and blood biochemistry data were obtained for this cross-sectional observational study. Anemia was defined as hemoglobin levels lower than 11.5 g/dl. Iron deficiency was defined as serum iron levels lower than 40 ug/dl. We also obtained data on parental education from questionnaires and on children's diets from 3-day food diaries. Parental education was categorized as low or high, with the latter representing an educational level beyond high school. RESULTS: Children with more educated mothers were less likely to develop anemia (P = 0.0324) and iron deficiency (P = 0.0577) than were those with less educated mothers. This group consumed more protein (P = 0.0004) and iron (P = 0.0012) from animal sources than did the children of less educated mothers, as reflected by their greater consumption of meat, poultry, and derivatives (P < 0.0001). Logistic regression analysis revealed a significant inverse relationship between maternal education and the prevalence of anemia (odds ratio: 0.52; 95% confidence interval: 0.32, 0.85). CONCLUSIONS: As a contributor to socioeconomic status, maternal education is important in reducing the risk of anemia and iron deficiency and in increasing children's consumption of animal food sources. PMID- 22087565 TI - The EFSA health claims 'learning experience'. AB - The European Food Safety Authority (EFSA) has recently highlighted the need to provide scientific requirements for health claims and to find new regulatory issues for healthy food products. For this reason, EFSA asked its Dietetic Products, Nutrition and Allergies (NDA) panel to draft additional guidelines on scientific assessment of these claims. A new approach for a strict substantiation of health issues in selected fields: the Regulation (EC) No. 1924/2006 established in fact that health claims applications should only be authorized after a high level of scientific validation conducted by EFSA using appropriate measures in this evaluation. The legislation should not only protect consumers but also define specific research areas with appropriate outcome measures to assess the quality, relevance and adequacy of studies conducted for scientific validation of health claims. The new system was not only a necessary support for consumers to make the correct choice of products, but rather a way for EFSA to demonstrate transparency of this new approach. This was the field of the pharmaceutical industry, this new regulation is, therefore, also for EFSA, an expensive learning process. PMID- 22087566 TI - Self-repairing systems based on ionomers and epoxidized natural rubber blends. AB - The development of materials with the ability of intrinsic self-repairing after damage in a fashion resembling that of living tissues has important scientific and technological implications, particularly in relation to cost-effective approaches toward damage management of materials. Natural rubbers with epoxy functional groups in the macromolecular chain (ENR) and ethylene-methacrylic acid ionomers having acid groups partially neutralized with metal ions possess self repairing behavior following high energy impacts. This research investigates the self-repairing behavior of both ENR and ionomers during ballistic puncture test on the basis of their thermal and mechanical properties. Heterogeneous blending of ionomers and ENR have also been used here as a strategy to tune the thermal and mechanical properties of the materials. Interestingly, blends of sodium ion containing ionomer exhibit complete self-repairing behavior, whereas blends of zinc ion containing ionomer show limited mending. The chemical structure studied by FTIR and thermal analysis shows that both ion content of ionomer and functionality of ENR have significant influence on the self-repairing behavior of blends. The mobility of rubbery phases along with its interaction to ionomer phase in the blends significantly changes the mending capability of materials. The healing behavior of the materials has been discussed on the basis of their thermal, mechanical, and rheological tests for each materials. PMID- 22087567 TI - Phenotypic variation in a Chinese family with 46,XY and 46,XX 17alpha-hydroxylase deficiency. AB - BACKGROUND: 17alpha-hydroxylase deficiency is a rare autosomal recessive disorder characterized by sexual infantilism, amenorrhea, hypertension and hypokalemia, which is caused by mutations in the CYP17A1 gene. To date, more than 50 mutations in this gene have been described. METHODS: The clinical features and biochemical data of a pair of 46,XY and 46,XX Chinese siblings with 17alpha-hydroxylase deficiency from Singapore were studied. Direct DNA sequence analysis of the CYP17A1 gene was performed. RESULTS: There was significant phenotypic variation between the siblings. The proband (46,XY) presented classically with sexual infantilism, amenorrhea and hypertension. The younger sibling (46,XX) also presented with amenorrhea, but she had breast development and absence of hypokalemic hypertension. The same compound heterozygous mutations in CYP17A1 gene were identified in both patients. A missense mutation (P409R) was detected in exon 7, and a 9-bp deletion (D487-S488-F489del) was detected in exon 8. CONCLUSION: We confirmed the diagnosis of 17alpha-hydroxylase deficiency in these two patients. Both P409R and D487-S488-F489del have been described previously and are widely propagated in the Chinese population in East and Southeast Asia. We propose that the phenotypic expression of affected individuals with 17alpha hydroxylase deficiency is karyotype-dependent, with individuals having the 46,XX karyotype having less pronounced clinical symptoms. PMID- 22087568 TI - Silicon-based Lewis acid assisted cinchona alkaloid catalysis: highly enantioselective aza-Michael reaction under solvent-free conditions. AB - The study showed that a combination of an achiral silicon-based Lewis acid and chiral Lewis base, such as iodotrimethylsilane (TMSI) and cinchonine, generated a highly enantioselective catalyst system under solvent-free conditions which gave aromatic beta-amino ketones with up to >99% ee. Mechanistic studies demonstrate the enhanced asymmetric induction may be due to the combined and competitive activation of a carbonyl moiety of chalcone with cinchonine and the silicon-based Lewis acid in the aza-Michael reaction. PMID- 22087569 TI - The need for support services for family carers of people with motor neurone disease (MND): views of current and former family caregivers a qualitative study. AB - PURPOSE: Family carers provide the majority of home-based care for people with motor neurone disease (MND). Carers' need for, and use of, support services are not fully understood; this study aimed to explore, from a qualitative perspective, the views of current and former family carers of people with MND. METHODS: A qualitative study was undertaken in Northwest England, using narrative interviews with current (18) and former (10) carers of a family member with MND. An optional longitudinal element involving diary completion was offered to the current carers. Data were analyzed using a thematic framework approach. RESULTS: Carer's needs vary, but encompass the provision of information and training, availability of respite care, counselling, and access to trained paid-for carers. CONCLUSIONS: There is need for a range of support services to be made available from which carers can select those most appropriate for them. Some support services are not always available for carers of this client group. There is a need for carers to access greater manual handling and training for physical care. Without sufficient support, carer burden can be overwhelming which may impact on the place of care of the patient and ultimately has implications for health and social care services. PMID- 22087570 TI - In silico and in vitro genotoxicity evaluation of levofloxacin n-oxide, an impurity in levofloxacin. AB - Impurities in drug substances and drug products generally do not have beneficial effects and may impose a risk without associated benefit. Levofloxacin n-oxide is an impurity isolated from levofloxacin. However there is insufficient toxic information about levofloxacin n-oxide. This study investigates the genotoxicity of this impurity by in silico and in vitro methods. We used Derek, a commercial structure-activity relationship software package as an in silico tool. The results showed that there was a structural alert (quinolone-3-carboxylic acid or naphthyridine analogue) in this impurity. Then the mouse lymphoma assay (MLA) and chromosome aberration assay in Chinese hamster lung (CHL) cells were conducted in vitro. Both assays were conducted in the presence or absence of S-9 mix. The test impurity was not mutagenic in the test of MLA. While there was a statistically significant increase in the number of metaphase CHL cells with structural aberrations at the concentration of 1 mg/mL with S-9 mix, and the aberrations rate is 6.5%. It did not significantly increase the number of structural aberration in CHL cells in the presence (at other two doses) or absence of S-9 mix. Based on these assays, levofloxacin n-oxide could be controlled as a non genotoxic impurity despite the DEREK alert for quinolone-3-carboxylic acid or naphthyridine analogue. PMID- 22087571 TI - Carbon nanotube-based robust steamphobic surfaces. AB - The wetting behavior of a surface under steam condensation depends on its intrinsic wettability and micrometer or nanoscale surface roughness. A typical superhydrophobic surface may not be suitable as a steamphobic surface because of the nucleation and growth of water inside the valleys and thus the failure to form an air-liquid-solid composite interface. Here, we present the results of steam condensation on chemically modified nanostructured carbon nanotube (CNT) mats. We used a plasma-enhanced chemical vapor deposition (PECVD) process to modify the intrinsic wettability of nanostructured CNT mats. The combination of low surface energy achieved by PECVD and the nanoroughness of the surface provides a mechanism to retain the superhydrophobicity of the CNT mats under steam condensation. The ability to withstand steam temperature and pressure for as long as 10 h implies the remarkably improved stability of the superhydrophobic state of the surface. The thermodynamic calculations carried out using a unit cell model clearly explain the steamphobic wetting behavior of the surface. PMID- 22087572 TI - Neuropsychological assessment: principles, rationale, and challenges. AB - Neuropsychological assessments are increasingly in demand for a wide range of patients. This paper offers a survey of the basic aspects of neuropsychological assessment that are of greatest importance for professionals (e.g., psychologists, psychiatrists, social workers, and lawyers) who are not trained in neuropsychological testing, but who refer clients for neuropsychological assessment. This survey could also serve neuropsychologists in their early stages of training, by addressing some of the major issues related to the assessment process. The range of goals that neuropsychological assessment may attain is first outlined. Next, a model is presented that explains the rationale enabling generalization from assessment to real-world functions that are the focus of interest and the target of prediction. Issues that need to be considered before deciding to conduct a neuropsychological evaluation are then introduced, and sources of information available to the assessor are described. A description is provided of what a neuropsychological assessment includes, with an emphasis on its cognitive aspects. Finally, mention is made of some of the difficulties and challenges that must be confronted in the course of a neuropsychological assessment. PMID- 22087573 TI - Role of clinical judgment and tissue harmonic imaging ultrasonography in diagnosis of paediatric acute appendicitis. AB - BACKGROUND: Appendicitis is the most common surgical emergency in children; yet, diagnosis of equivocal presentations continues to challenge clinicians. AIM: The objective of this study was to investigate the hypothesis that the use of a modified clinical practice and harmonic ultrasonographic grading scores (MCPGS) may improve the accuracy in diagnosing acute appendicitis in the pediatric population. PATIENTS & METHODS: MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of the modified scoring system. Five hundred and thirty patients presented with suspected diagnosis of acute appendicitis during the period from December 2000 to December 2009 were enrolled in this study. Children's data that have already been published of those who presented with suspected diagnosis of acute appendicitis- to whom a special clinical practice grading scores (CPGS) incorporating clinical judgment and results of gray scale ultrasonography (US) was applied- were reviewed and compared to the data of 265 pediatric patients with equivocal diagnosis of acute appendicitis (AA), to whom a modified clinical practice grading scores (MCPGS) was applied. Statistical analyses were carried out using Z test for comparing 2 sample proportions and student's t-test to compare the quantitative data in both groups. Sensitivity and specificity for the 2 scoring systems were calculated using Epi-Info software. RESULTS: The Number of appendectomies declined from 200 (75.5%) in our previous CPGS to 187 (70.6%) in the MCPGS (P > 0.05).Specificity was significantly higher when applying MCPGS (90.7%) in this study compared to 70.47% in our previous work when CPGS was applied (P < 0.01). Furthermore, the positive predictive value (PPV) was significantly higher (95.72%) than in our previous study (82.88%), (P < 0.01). Overall agreement (accuracy) of MCPGS was 96.98%. Kappa = 0.929 (P < 0.001). Negative predictive power was 100%. And the Overall agreement (accuracy) was 96.98%. CONCLUSIONS: MCPGS tends to help in reduce the numbers of avoidable and unnecessary appendectomies in suspected cases of pediatric acute appendicitis that may help in saving hospital resources. PMID- 22087574 TI - Belief in a just world, generalised self-efficacy and stigma may contribute to unsafe sexual intentions via a reduced perception of vulnerability to HIV/AIDS amongst young people in Ghana. AB - Complacency about one's HIV risk status may reduce the intention to practise safe sex. It was hypothesised that belief in a just world and stigmatising attitudes may contribute to complacency and thereby have a negative impact on safe sex intention. A sample of 238 young people in Ghana, ranging in age from 14 to 22, completed the Generalised Self-Efficacy Scale and the Belief in a Just World Scales for Self and Other, together with self-report measures of stigmatising attitudes, perceived vulnerability to HIV/AIDS and intentions to practise safe sex. Mediation analysis supported the hypothesis that stigma and just world beliefs may have a negative impact on safe sex intention that is mediated by a reduced perception of vulnerability. It was also found that generalised self efficacy beliefs had a similar mediated impact. Each of the three factors had a mediated impact that was relatively independent of the other two factors. In addition, stigma had a negative direct (unmediated) effect on safe sex intention (i.e., more stigma was associated with reduced safe sex intention); but generalised self-efficacy beliefs had a positive direct effect (i.e., greater belief was associated with increased safe sex intention). The study replicates some previous research about stigma, and provides new evidence about the role of just world and generalised self-efficacy beliefs. Implications for public health programmes are discussed. PMID- 22087575 TI - Alcohol use and psychiatric comorbid disorders predict deliberate self-harm behaviour and other suicidality among depressed adolescent outpatients in 1-year follow-up. AB - BACKGROUND: Suicidality, including deliberate self-harm behaviour (DSH), represents one of the most adverse and clinically serious consequences of depression. More detailed longitudinal research is needed in order to find clinical risk factors of DSH and other suicidal behaviour among depressed adolescent outpatients in order to identify those at greatest risk of life threatening behaviour. AIM: This follow-up study investigated alcohol use, Axis I comorbid disorders, depressive and anxiety symptoms, and psychosocial functioning as risk factors of suicidal behaviour, including DSH, among depressed adolescent outpatients during a 1-year follow-up. METHODS: Consecutive depressed adolescent outpatients (n = 189) aged 13-19 years were interviewed at baseline and at follow up by using the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime (K-SADS-PL) for DSM-IV Axis I diagnoses and self-report questionnaires. Suicidal behaviour was assessed by K-SADS suicidality items. RESULTS: During 1-year follow-up, one-quarter of all participants, and almost three-quarters of suicidal adolescents had DSH. Alcohol use and mood disorder with Axis I comorbidity at baseline predicted both DSH and other suicidal behaviour during follow-up. Mood disorder during follow-up predicted all forms of suicidal behaviour. CONCLUSIONS: Detection and effective treatment of continuing mood disorder, comorbid disorders and alcohol use may significantly improve clinician's ability to identify adolescent outpatients at high risk of subsequent DSH and other suicidal behaviour. Treatment interventions should aim at full recovery of depression. PMID- 22087576 TI - The effect of adding whole-body vibration to squat training on the functional performance and self-report of disease status in elderly patients with knee osteoarthritis: a randomized, controlled clinical study. AB - OBJECTIVES: The study objectives were to evaluate the effects of adding whole body vibration to squat training on functional performance and self-report of disease in elderly individuals with knee osteoarthritis (OA). DESIGN: This was a prospective, randomized trial in which selected variables were evaluated at three periods: 3 weeks prior to the training, immediately prior, and after the end of the training. SUBJECTS: Twenty-three (23) elderly subjects were evaluated using four functional performance tests: Berg Balance Scale (BBS), Timed Get Up and Go Test (TGUG), Chair Stand Test (CST), and 6-Minute Walk Test (6MWT), and a self report of the status of disease (WOMAC). INTERVENTIONS: The intervention lasted for 12 weeks, 3 times per week. The participants were randomized into two groups: (1) squat training with whole-body vibration, and (2) squat training without vibration. RESULTS: Although there was no statistical difference in functional performance and self-report of disease status between the groups, performance in all the functional tests and in all the domains of WOMAC improved in the vibration group compared to their initial status. In the exercise group, performance improved only two tests (BBS and 6MWT), and there was a reduction in self-reported pain (WOMAC) compared to their initial status. CONCLUSIONS: Although the addition of whole-body vibration to squat training failed to result in a significant improvement in functional performance and self-reported status of knee osteoarthritis in the elderly, the intragroup results suggest that whole body vibration may represent a feasible and effective way of improving the functionality and self-perception of disease status in older adults with knee OA. PMID- 22087577 TI - The use of insulin in elderly patients with type 2 diabetes mellitus. AB - INTRODUCTION: Older patients with diabetes sometimes present comorbidities that increase the risk of other common geriatric syndromes. In such patients, treatment with insulin is usually started when full doses of oral hypoglycemic agents are no longer adequate to achieve acceptable glycemic control. AREAS COVERED: This article reviews the available literature on the use of insulin in elderly patients with type 2 diabetes. The aims are to gain information on: the benefits and risks of initiating insulin treatment, the efficacy and safety of different types of insulin and the most appropriate initial dosing and titration regimens. Thirteen published trials have evaluated the effects of different insulin regimens in the management of elderly subjects with type 2 diabetes but, given that older people are generally excluded in clinical studies with insulin, only three published reports on subgroup analyses are limited to elderly patients. EXPERT OPINION: The available literature shows that the addition of insulin to current oral treatments is generally safe and effective in improving metabolic control, with a low risk for hypoglycemia. Further research is needed to better understand the most appropriate insulin regimens necessary to achieve glycemic goals while appropriately addressing the risk of hypoglycemia. PMID- 22087578 TI - IL-6 and soluble IL-6 receptor stimulate the production of MMPs and their inhibitors via JAK-STAT and ERK-MAPK signalling in human chondrocytes. AB - Elevated concentrations of IL-6 (interleukin-6) and sIL-6r (soluble IL-6 receptor) in the synovial fluid and serum of patients with arthritis have been implicated in joint cartilage destruction. This study examined the effects of IL 6 and sIL-6r on the expression of MMPs (matrix metalloproteinases), TIMPs (tissue inhibitor of metalloproteinases), the plasminogen activation system including tPA (tissue-type PA), uPA (urokinase-type PA) and PAI-1 (PA inhibitor type 1) using chondrocytes derived from normal human femur cartilage. The cells were cultured with or without 50 ng/ml IL-6 and/or 30 ng/ml sIL-6r in the presence or absence of the JAK3 (Janus kinase 3) inhibitor WHI-P131 or the MEK [MAPK (mitogen activated protein kinase)/ERK (extracellular signal protein kinase) kinase] inhibitor PD98059 for up to 28 days. The expression of MMPs, TIMPs, uPA, tPA and PAI-1 was investigated at the mRNA and protein levels. MMP protein expression and pSTAT3 (phosphorylation of signal transducer and activator of transcription 3) and pERK (phosphorylation of ERK) were also measured. Treatment with both IL-6 and sIL-6r markedly increased the expression of MMP-1, MMP-13, TIMP-1 and PAI-1, while significantly decreasing the expression of tPA and uPA and stimulating pSTAT3 and pERK. Adding WHI-P131 or PD98059 decreased IL-6 and sIL-6r enhancement of MMP-1, -3 and -13. The results suggest that IL-6 and sIL-6r stimulate the production of MMPs and their inhibitor via JAK-STAT and ERK-MAPK signalling in chondrocytes. PMID- 22087580 TI - Spindles and active vortices in a model of confined filament-motor mixtures. AB - BACKGROUND: Robust self-organization of subcellular structures is a key principle governing the dynamics and evolution of cellular life. In fission yeast cells undergoing division, the mitotic spindle spontaneously emerges from the interaction of microtubules, motor proteins and the confining cell walls, and asters and vortices have been observed to self-assemble in quasi-two dimensional microtubule-kinesin assays. There is no clear microscopic picture of the role of the active motors driving this pattern formation, and the relevance of continuum modeling to filament-scale structures remains uncertain. RESULTS: Here we present results of numerical simulations of a discrete filament-motor protein model confined to a pressurised cylindrical box. Stable spindles, nematic configurations, asters and high-density semi-asters spontaneously emerge, the latter pair having also been observed in cytosol confined within emulsion droplets. State diagrams are presented delineating each stationary state as the pressure, motor speed and motor density are varied. We further highlight a parameter regime where vortices form exhibiting collective rotation of all filaments, but have a finite life-time before contracting to a semi-aster. Quantifying the distribution of life-times suggests this contraction is a Poisson process. Equivalent systems with fixed volume exhibit persistent vortices with stochastic switching in the direction of rotation, with switching times obeying similar statistics to contraction times in pressurised systems. Furthermore, we show that increasing the detachment rate of motors from filament plus-ends can both destroy vortices and turn some asters into vortices. CONCLUSIONS: We have shown that discrete filament-motor protein models provide new insights into the stationary and dynamical behavior of active gels and subcellular structures, because many phenomena occur on the length-scale of single filaments. Based on our findings, we argue the need for a deeper understanding of the microscopic activities underpinning macroscopic self-organization in active gels and urge further experiments to help bridge these lengths. PMID- 22087579 TI - Impact of an abdominal belt on breathing patterns and scan efficiency in whole heart coronary magnetic resonance angiography: comparison between the UK and Japan. AB - BACKGROUND: Long acquisition times and complex breathing motion patterns lead to suboptimal image quality in whole heart coronary magnetic resonance angiography (WHCMRA). To overcome this problem, an abdominal belt (BELT) has been suggested by a Japanese group. However, its applicability in a Western population has not been previously demonstrated. The purpose of this study was to investigate 1) how the application of a BELT alters breathing patterns during MR scanning and 2) whether the BELT has a similar impact on breathing patterns in UK and Japanese patient populations. METHODS: 30 patients (15 in the UK and 15 in Japan) were studied at 1.5 Tesla (Achieva, Philips Healthcare). Real time navigator positioned through the right diaphragm in cranio-caudal direction was evaluated. Measurements were performed in the supine position with free breathing for one minute before and after a tight-fitting BELT was positioned around the patient's abdomen. End expiratory position (EEP), end inspiratory position (EIP), end expiratory duration (EED) for the right diaphragm and respiratory rate (RR) were obtained. Scan efficiency (SE) was calculated as follows; SE = [the duration within 5 mm gating window per minutes]/[RR interval]/[heart rate]. RESULTS: Height and weight of UK patients were significantly larger than in the Japanese population (171.2 +/- 10.8 cm vs 160.8 +/- 8.5 cm, p = 0.007; 80.5 +/- 22.5 kg vs 59.9 +/- 7.7 kg, p = 0.004). After fitting the BELT, EEP-EIP decreased (all patients, 14.9 +/- 6.2 mm to 9.4 +/- 3.8 mm, p < 0.001; UK patients, 15.9 +/- 6.0 mm to 9.7 +/- 3.1 mm, p = 0.001; Japanese patients, 14.0 +/- 6.4 mm to 9.1 +/- 4.6 mm, p = 0.001), RR increased (all patients, 10.0 +/- 3.1 min(-1) to 11.2 +/- 3.0 min(-1), p = 0.003; UK patients, 9.5 +/- 2.8 min(-1) to 10.7 +/- 2.8 min(-1), p = 0.038; Japanese patients, 10.4 +/- 3.5 min(-1) to 11.8 +/- 3.1 min(-1), p = 0.036), and calculated scan efficiency increased (all patients, 45.3 +/- 11.4% to 58.6 +/- 17.0%, p < 0.001; UK patients, 44.2 +/- 10.8% to 55.7 +/- 16.7%, p = 0.004; Japanese patients, 46.3 +/- 32.2% to 61.0 +/- 17.6%, p = 0.001). No significant differences were found between UK and Japanese patients before and after administration of the BELT. CONCLUSION: Using a BELT significantly increases whole-heart coronary MR angiography scan efficiency in both UK and Japanese patients. PMID- 22087581 TI - Mental health and behaviour of students of public health and their correlation with social support: a cross-sectional study. AB - BACKGROUND: Future public health professionals are especially important among students partly because their credibility in light of their professional messages and activities will be tested daily by their clients; and partly because health professionals' own lifestyle habits influence their attitudes and professional activities. A better understanding of public health students' health and its determinants is necessary for improving counselling services and tailoring them to demand. Our aim was to survey public health students' health status and behaviour with a focus on mental health. METHODS: A cross-sectional study was carried out among public health students at 1-5-years (N = 194) with a self administered questionnaire that included standardized items on demographic data, mental wellbeing characterized by sense of coherence (SoC) and psychological morbidity, as well as health behaviour and social support. Correlations between social support and the variables for mental health, health status and health behaviour were characterized by pairwise correlation. RESULTS: The response rate was 75% and represented students by study year, sex and age in the Faculty. Nearly half of the students were non-smokers, more than one quarter smoked daily. Almost one-fifth of the students suffered from notable psychological distress. The proportion of these students decreased from year 1 to 5. The mean score for SoC was 60.1 and showed an increasing trend during the academic years. 29% of the students lacked social support from their student peers. Significant positive correlation was revealed between social support and variables for mental health. Psychological distress was greater among female public health students than in the same age female group of the general population; whereas the lack of social support was a more prevalent problem among male students. CONCLUSIONS: Health status and behaviour of public health students is similar to their non-students peers except for their worse mental health. Future public health professionals should be better prepared for coping with the challenges they face during their studies. Universities must facilitate this process by providing helping services targeted at those with highest risk, and developing training to improve coping skills. Social support is also a potentially amenable determinant of mental health during higher education. PMID- 22087582 TI - Enhanced photoluminescence in Au-embedded ITO nanowires. AB - Gold (Au)-embedded indium tin oxide (ITO) nanowires were synthesized by thermal evaporation of a mixture of In(2)O(3,) SnO(2) and graphite powders on Si (100) substrates coated with Au thin films followed by annealing. At the initial stages of annealing, Au formed a continuous linear core located along the long axis of each ITO nanowire. The morphology of the Au core changed from a continuous line to a discrete line, and then to a droplet-like chain, finally evolving into a peapod in which crystalline Au nanoparticles were encapsulated in crystalline ITO with increasing annealing temperature. The ITO nanowires with the Au core showed an emission band at ~380 nm in the ultraviolet region. The ultraviolet emission intensity increased rapidly with increasing annealing temperature. The intensity of emission from the Au-peapod ITO nanowires (annealed at 750 degrees C) was approximately 20 times higher than that of the emission from the Au-core/ITO shell ITO nanowires with a continuous linear shaped-Au core (annealed at 550 degrees C). This ultraintense ultraviolet emission might have originated mainly from the enhanced crystalline quality of the annealed ITO nanowires. PMID- 22087583 TI - Remarkable stereospecific conjugate additions to the Hsp90 inhibitor celastrol. AB - Celastrol, an important natural product and Hsp90 inhibitor with a wide range of biological and medical activities and broad use as a biological probe, acts by an as yet undetermined mode of action. It is known to undergo Michael additions with biological sulfur nucleophiles. Here it is demonstrated that nucleophiles add to the pharmacophore of celastrol in a remarkable stereospecific manner. Extensive characterization of the addition products has been obtained using NMR spectrometry, nuclear Overhauser effects, and density functional theory to determine facial selectivity and gain insight into the orbital interactions of the reactive centers. This stereospecificity of celastrol may be important to its protein target selectivity. PMID- 22087584 TI - Structure change induced by terminal sulfur in noncentrosymmetric La2Ga2GeS8 and Eu2Ga2GeS7 and nonlinear-optical responses in middle infrared. AB - Two new noncentrosymmetric quaternary sulfides, La(2)Ga(2)GeS(8) (1) and Eu(2)Ga(2)GeS(7) (2), have been synthesized by high-temperature solid-state reactions. The structure change on going from 1 to 2 to the known Li(2)Ga(2)GeS(6) (3) nicely shows that the reduced cation charge-compensation requirement causes a decrease in the number of terminal S atoms per formula, which is a key to determining the connectivity of the GaS(4) and GeS(4) building units. Powder sample 2 exhibits a strong second-harmonic-generation (SHG) response of about 1.6 times the benchmark AgGaS(2) at 2.05 MUm laser radiation, a non type I phase-matchable behavior, and a comparable transparency region. The SHG intensities of these compounds originate from the electronic transitions from S 3p states to La/Eu/Li-S, Ga-S, and Ge-S antibonding states according to Vienna ab initio simulation package studies. PMID- 22087585 TI - Lipid-altering effects of a dietary supplement tablet containing free plant sterols and stanols in men and women with primary hypercholesterolaemia: a randomized, placebo-controlled crossover trial. AB - This randomized, placebo-controlled, crossover trial assessed the lipid-altering efficacy of a dietary supplement (tablet form) providing 1.8 g/day free (non esterified) plant sterols and stanols versus placebo for 6 weeks as part of a therapeutic lifestyle changes (TLC) diet in 32 men and women with primary hypercholesterolaemia. Mean +/- SE baseline (end of a 5-week TLC diet lead-in) lipid concentrations (mmol/l) were total cholesterol (TC), 5.88 +/- 0.08; non high-density lipoprotein cholesterol (non-HDL-C), 4.71 +/- 0.09; low-density lipoprotein cholesterol (LDL-C), 4.02 +/- 0.08; HDL-C, 1.17 +/- 0.06 and triglycerides (TGs), 1.51 +/- 0.12. Differences from control in responses (plant sterol/stanol - control) were significant (p < 0.05) for LDL-C ( - 4.9%), non-HDL C ( - 3.6%) and TC ( - 2.8%). HDL-C and TG responses were not significantly different between treatment conditions. These results indicate that 1.8 g/day free plant sterols/stanols administered in a tablet produced favourable lipoprotein lipid changes in men and women with hypercholesterolaemia. PMID- 22087586 TI - Measurement of gender inequality in neighbourhoods of Quebec, Canada. AB - INTRODUCTION: Few studies have measured gender inequality at levels lower than the country. We sought to develop neighbourhood indicators of gender inequality, and assess their ability to capture variability in gender inequality across Quebec, Canada. METHODS: Aggregate 2001 census data for 11,564 neighbourhoods were obtained for men and women. Twelve indicators of gender inequality representing demographic/household characteristics, education, income, work/leisure, and political participation were selected. Neighbourhood-level gender inequality scores were computed for each indicator, and examined across parts of Quebec (metropolitan areas, mid-sized cities, rural areas). Monte Carlo simulations were used to assess the ability of indicators to capture heterogeneity in gender inequality across neighbourhoods. RESULTS: Male-dominant neighbourhood-level gender inequality tended to be present for average employment income, labour force participation, employment rate, and employment in managerial positions. Female-dominant gender inequality tended to be present for divorce, single-headed households, and participation in unpaid housework, child and elderly care. Neighbourhood-level gender inequality tended to vary across metropolitan areas, mid-sized cities, and rural areas. Gender inequality scores also varied within these geographic areas. For example, there was greater income related gender inequality in high than low income neighbourhoods. Monte Carlo simulations suggested that the variation in gender inequality across neighbourhoods was greater than expected with chance alone. CONCLUSION: Neighbourhood-level gender inequality tended to be present in Quebec, and varied across parts of the province. Greater awareness of and research on neighbourhood level gender inequality may be warranted to inform gender policies in Quebec and other nations. PMID- 22087587 TI - Use of venlafaxine in psychiatric disorders and climacteric syndrome: is a therapeutic bridge? AB - OBJECTIVE: To verify the efficacy of the double-action mechanism of venlafaxine for depression and climacteric symptoms. METHODS: A group of 20 postmenopausal women (age range 40-60 years) with diagnosis of major depressive disorder, generalized anxiety disorder and climacteric symptoms was enrolled. All participants received venlafaxine (75 mg/day) for 2 months. Clinical checkup and evaluation test were repeated every 2 weeks for 2 months of treatment. RESULTS: Before treatment, the mean scores for the clinical evaluation scales (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale) were 13.9 and 18.7, respectively (mild-moderate severity). The general level of psychopathology was not particularly high (Symptomatology Checklist-90, mean total 103), the most common psychopathological dimensions were depression and somatization. The sample suffered from mild climacteric syndrome (Kupperman Index Score, mean = 19.1). Clinical improvement was visible after 2 weeks of treatment and continued until the last checkup, 2 months after the start of treatment (final Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores: 5.1 and 6.3, respectively). Kupperman Index Scores at the end of the treatment period demonstrated complete resolution of the climacteric syndrome (mean score = 6.57). CONCLUSION: Venlafaxine is efficacy in treating both psychiatric disorders and climacteric symptomatology. PMID- 22087588 TI - Rationalizing tight ligand binding through cooperative interaction networks. AB - Small modifications of the molecular structure of a ligand sometimes cause strong gains in binding affinity to a protein target, rendering a weakly active chemical series suddenly attractive for further optimization. Our goal in this study is to better rationalize and predict the occurrence of such interaction hot-spots in receptor binding sites. To this end, we introduce two new concepts into the computational description of molecular recognition. First, we take a broader view of noncovalent interactions and describe protein-ligand binding with a comprehensive set of favorable and unfavorable contact types, including for example halogen bonding and orthogonal multipolar interactions. Second, we go beyond the commonly used pairwise additive treatment of atomic interactions and use a small world network approach to describe how interactions are modulated by their environment. This approach allows us to capture local cooperativity effects and considerably improves the performance of a newly derived empirical scoring function, ScorpionScore. More importantly, however, we demonstrate how an intuitive visualization of key intermolecular interactions, interaction networks, and binding hot-spots supports the identification and rationalization of tight ligand binding. PMID- 22087589 TI - Attraction of night-migrating birds to light-blue structures causes mass bird deaths. PMID- 22087590 TI - Using J-coupling constants for force field validation: application to hepta alanine. AB - A computational solution to the protein folding problem is the holy grail of biomolecular simulation and of the corresponding force fields. The complexity of the systems used for folding simulations precludes a direct feedback between the simulations and the force fields, thus necessitating the study of simpler systems with sufficient experimental data to allow force field optimization and validation. Recent studies on short polyalanine peptides of increasing length (up to penta-alanine) indicated the presence of a systematic deviation between the experimental (NMR-derived) J-couplings and the great majority of biomolecular force fields, with the chi(2) values for even the best-performing force fields being in the 1.4-1.8 range. Here we show that by increasing the number of residues to seven and by achieving convergence through an increase of the simulation time to 2 MUs, we can identify one force field (the AMBER99SB force field, out of the three force fields studied) which when compared with the experimental J-coupling data (and for a specific set of Karplus equation parameters and estimated J-coupling errors previously used in the literature) gave a value of chi(2) = 0.99, indicating that full statistical consistency between experiment and simulation is feasible. However, and as a detailed analysis of the effects of estimated errors shows, the chi(2) values may be unsuitable as indicators of the goodness of fit of the various biomolecular force fields. PMID- 22087591 TI - Bifunctional 3,3'-Ph2-BINOL-Mg catalyzed direct asymmetric vinylogous Michael addition of alpha,beta-unsaturated gamma-butyrolactam. AB - Bifunctional 3,3'-Ph(2)-BINOL-Mg catalyzed direct asymmetric vinylogous Michael addition of alpha,beta-unsaturated gamma-butyrolactam has been developed. The catalytic activity of this protocol was slightly affected by different types of Michael acceptors, such as a variety of enones as well as alpha,beta-unsaturated N-acylpyrroles. The Michael products were obtained with high diastereoselectivities (up to 20:1) and excellent enantioselectivities (up to 98%). PMID- 22087592 TI - Mind, self, country, and global society. PMID- 22087593 TI - The feminization of aging: how will this impact on health outcomes and services? AB - We conducted an integrative review to identify issues and challenges that face aging women and to distinguish areas for future research. We found that many older women continue to face inequities related to health and often are invisible within the discourse of aging policy. In this article we argue for a greater focus on the unique needs of women, a gendered approach to policy and intervention development, and promotion of the health of women across the life span. Policymakers, health care workers, and researchers need to consider the perspective of gender as well as age when implementing and evaluating effective interventions. PMID- 22087594 TI - "They're made in factories and not by witches on the allotment": a qualitative study of midlife women in the united kingdom, exploring their approaches to complementary and alternative medicines. AB - This article explores midlife women's experiences and approaches related to complementary and alternative therapies (CAMS). Ninety-six midlife women were asked about their use of CAMs as part of their overall approach to midlife health. Qualitative thematic analysis was combined with a case-based approach. Women set their experience of CAMs in the context of conventional medicine taking and discussed their safety and different uses. For treatments requiring direct contact with a practitioner, accessibility and quality of the relationship were crucial. Four overall approaches could be discerned (political-critical, pragmatic, careful and wellbeing-oriented) that dynamically interacted with women's experiences. PMID- 22087595 TI - Comparison of body composition measurement with whole body multifrequency bioelectrical impedance and air displacement plethysmography in healthy middle aged women. AB - Our purpose was to evaluate accuracy of multifrequency bioelectrical impedance analysis (MFBIA) using air displacement plethysmography (ADP) as the criterion measure. Body composition of 27 women was assessed by ADP followed immediately by MFBIA. There was a strong relationship (p = .01) between ADP and MFBIA in absolute lean mass (r = 0.80), absolute fat mass (r = 0.99), percent lean mass (r = 0.91), and percent fat mass (r = 0.91). Although MFBIA consistently overestimated lean mass and underestimated fat mass compared with ADP, agreement between measurements was within 2%-3% body fat. An accurate assessment tool, MFBIA can be useful in clinical settings. PMID- 22087596 TI - Body mass index in multiethnic midlife women: influence of demographic characteristics and physical activity. AB - We examined the influence of demographic characteristics and physical activity on body mass index (BMI) in multiethnic midlife women. A sample of 236 African, European, and Mexican/Central Americans aged 40-50 completed the initial, 1-year, and 2-year assessments. The effects of demographic characteristics and physical activity on BMI at the 2-year assessment were evaluated using hierarchical multiple regression analysis. After controlling for other demographic factors, ethnicity, annual household income, and physical activity at the initial assessments were significant predictors of BMI. Body mass index (BMI) may be influenced by socioeconomic status as well as ethnicity. Regular physical activity should be encouraged to maintain a healthy BMI in midlife women. PMID- 22087597 TI - Improving access to government health care in rural bangladesh: the voice of older adult women. AB - Our purpose in this study was to provide an in-depth understanding of the health system-related barriers to utilization of health services by older women living in rural Bangladesh. Interviews were conducted with 17 women in Bibirchar Union, Sherpur district, Bangladesh, in June 2006. Three main barriers were identified: perceived discrimination based on age, class, and gender; structural aspects of the health care delivery system; and quality of care. Recommendations for change in the delivery of health care in the rural regions of Bangladesh are made based on the insights provided by this marginalized group of health care service users. PMID- 22087598 TI - Representations and perceived consequences of menopause by peri- and post menopausal portuguese women: a qualitative research. AB - Our aim in conducting this study is to describe the representations and perceived consequences of menopause, elicited through a semistructured interview with 36 Portuguese women, in peri- and post-menopause. The most prevalent response of the interviewed women was to see menopause as a normal/neutral phase of their life cycle (28.3%). Menses' cessation (58.7%) was identified as the most prevalent positive consequence of menopause, and a range of psychological changes (18.3%) was the most mentioned negative consequence. Health care provider's awareness of women's attitudes will allow them to communicate more effectively and to reinforce women's positive attitudes. PMID- 22087601 TI - Can hip-fractured elderly patients maintain their rehabilitation achievements after 1 year? AB - PURPOSE: The purpose of this study is to characterize hip-fractured patients who maintained or improved their functional ability, 1 year postdischarge from rehabilitation and to identify factors associated with functional achievement maintenance. METHODS: A retrospective study performed in a postacute geriatric rehabilitation center. Two hundred thirty-three hip-fractured patients admitted consecutively from January 2006 to September 2007 were enrolled in the study. The patients were evaluated at discharge from rehabilitation and after 1 year, they were classified into two groups: those who maintained or improved their motor Functional Independence Measure (mFIM) scores and those who deteriorated. The differences between the two patient groups relating to functional, clinical, demographic and fracture-related variables were assessed. RESULTS: One year postrehabilitation, 130 (55.8%) patients exhibited a decline in their mFIM score. Patients whose 1-year mFIM score had improved were discharged from rehabilitation with a less favorable mean mFIM score (50.7 +/- 18.5 vs. 55.6 +/- 15.2; p = 0.032), achieved a lower mean mFIM score gain during rehabilitation (12.0 +/- 9.7 vs. 14.6 +/- 8.1; p = 0.03), had a higher education level (p = 0.003) and had a lower rate of chronic lung disease (p = 0.020) compared with patients whose 1 year mFIM score had deteriorated. After 1 year, only 21 patients (9%) were functionally independent in activities of daily living and only 19 (8.2%) were able to walk unassisted. Only 13 patients (5.6%) perceived that they had regained their former functional level. CONCLUSIONS: A substantial decline in functional ability of hip-fractured patients occurred 1 year postdischarge from rehabilitation. Healthcare providers should be aware of the necessity for a long term postrehabilitation physical training program to prevent functional decline. Further efforts should be invested in motivating their patients to exercise. PMID- 22087603 TI - The characteristics of the mechanoreceptors of the hip with arthrosis. AB - Mechanoreceptors have been extensively studied in different joints and distinct signals that convey proprioceptive information to the cortex. Several clinical reports have established a link between the number of mechanoreceptors and a deficient proprioceptive system; however, little or no literature suggest concentration of mechanoreceptors might be affected by hip arthrosis. The purpose of this study is first to determine the existence of mechanoreceptors and free nerve endings in the hip joint and to distinguish between their conditions: those with arthrosis and without arthrosis. Samples of 45 male hips were analyzed: 30 taken from patients with arthrosis that were submitted to total arthroplasty and 15 taken from male cadavers without arthrosis. The patients' ages ranged from 38 to75 years (average 56.5) and the cadavers' ages ranged from 21 to 50 years (average 35.5). The capsule, labrum, and femoral head ligament tissues were obtained during the arthroplasty procedure from 30 patients with arthrosis and from 15 male cadavers. The tissue was cut into fragments of around 3 mm. Each fragment was then immediately stained with gold chloride 1% solution and divided into sections of 6 MUm thickness. The Mann-Whitney test was used for two groups and the ANOVA, Friedman and Kruskal-Wallis tests for more than two groups. Results show the mechanoreceptors (Pacini, Ruffini and Golgi corpuscles) and free nerve endings are present in the capsule, femoral head ligament, and labrum of the hip joint. When all the densities of the nerve endings were examined with regard to those with arthrosis and those without arthrosis, the mechanoreceptors of cadavers without arthrosis were found to be more pronounced and an increase in free nerve endings could be observed (p = 0.0082). Further studies, especially electrophysiological studies, need to be carried out to clarify the functions of the mechanoreceptors in the joints. PMID- 22087604 TI - Level of dietary protein intake affects glucose turnover in endurance-trained men. AB - BACKGROUND: To examine the effects of higher-protein diets on endogenous glucose metabolism in healthy, physically active adults, glucose turnover was assessed in five endurance-trained men (age 21.3 +/- 0.3 y, VO2peak 70.6 +/- 0.1 mL kg-1 min 1) who consumed dietary protein intakes spanning the current dietary reference intakes. FINDINGS: Using a randomized, crossover design, volunteers consumed 4 week eucaloric diets providing either a low (0.8 g kg-1 d-1; LP), moderate (1.8 g kg-1 d-1; MP), or high (3.6 g kg-1 d-1; HP) level of dietary protein. Glucose turnover (Ra, glucose rate of appearance; and Rd glucose rate of disappearance) was assessed under fasted, resting conditions using primed, constant infusions of [6,6-2H2] glucose. Glucose Ra and Rd (mg kg-1 min-1) were higher for MP (2.8 +/- 0.1 and 2.7 +/- 0.1) compared to HP (2.4 +/- 0.1 and 2.3 +/- 0.2, P < 0.05) and LP (2.3 +/- 0.1 and 2.2 +/- 0.1, P < 0.01) diets. Glucose levels (mmol/L) were not different (P > 0.05) between LP (4.6 +/- 0.1), MP (4.8 +/- 0.1), and HP (4.7 +/- 0.1) diets. CONCLUSIONS: Level of protein consumption influenced resting glucose turnover in endurance athletes in a state of energy balance with a higher rate of turnover noted for a protein intake of 1.8 g kg-1 d-1. Findings suggest that consumption of protein in excess of the recommended dietary allowance but within the current acceptable macronutrient distribution range may contribute to the regulation of blood glucose when carbohydrate intake is reduced by serving as a gluconeogenic substrate in endurance-trained men. PMID- 22087605 TI - Nocturnal heart rate variability parameters as potential fibromyalgia biomarker: correlation with symptoms severity. AB - INTRODUCTION: At present, there is neither a laboratory test nor an imaging technique able to differentiate people with fibromyalgia (FM) from healthy controls. This lack of an objective biomarker has hampered FM recognition and research. Heart rate variability (HRV) analyses provide a quantitative marker of autonomic nervous system activity. Nighttime is a stable period in which most people are resting. Sleep is modulated by autonomic activity. Sleeping problems are prominent in FM. The objectives of this study are: 1) to explore different nocturnal HRV parameters as potential FM biomarkers and 2) to seek correlation between such HRV parameters and diverse FM symptoms. METHODS: We studied 22 women suffering from FM and 22 age-matched controls. All participants filled out several questionnaires related to FM symptoms. All participants used a Holter monitor over 24 hours while undertaking their routine activities during the day and while sleeping at their homes at night. Time-domain HRV parameters analyzed from 0000 to 0600 hours included, among others: mean normal-normal interbeat intervals (mean NN), standard deviation of the NN intervals (SDNN), and standard deviation of the successive NN differences (SDSD). RESULTS: Nocturnal SDNN of less than 114 ms had the greatest predictive value to set apart patients from controls with an odds ratio of 13.6 (95% confidence interval: 3.9 to 47.8). In patients, decreased nighttime HRV markers indicative of sympathetic predominance had significant correlations with several FM symptoms: SDSD was associated with pain intensity (r = -0.65, P = 0.001). SDNN correlated with constipation (r = 0.53, P = 0.001), and mean NN with depression (r = -0.53, P = 0.001). Controls displayed an opposite behavior. For them, increased nighttime SDNN correlated with Fibromyalgia Impact Questionnaire scores (r = 0.69, P = 0.001) and with other FM symptoms. CONCLUSIONS: Nocturnal HRV indices indicative of sympathetic predominance are significantly different in FM women when compared to healthy individuals. In FM patients, these HRV parameters correlated with several symptoms including pain severity. Opposite associations were seen in controls. FM may not be just one end of a continuous spectrum of common symptoms. Nocturnal HRV analyses are potential FM biomarkers. PMID- 22087606 TI - In vivo distribution of avidin-conjugated MX35 and (211)At-labeled, biotinylated poly-L-lysine for pretargeted intraperitoneal alpha-radioimmunotherapy. AB - PURPOSE: Avidin-coupled monoclonal antibody MX35 (avidin-MX35) and astatine-211 labeled, biotinylated, succinylated poly-l-lysine ((211)At-B-PL(suc)) were administered in mice to assess potential efficacy as an intraperitoneal (i.p.) therapy for microscopic tumors. We aimed to establish a timeline for pretargeted radioimmunotherapy using these substances, and estimate the maximum tolerable activity. METHODS: (125)I-avidin-MX35 and (211)At-B-PL(suc) were administered i.p. in nude mice. Tissue distributions were studied at various time points and mean absorbed doses were estimated from organ uptake of (211)At-B-PL(suc). Studies of myelotoxicity were performed after administration of different activities of (211)At-B-PL(suc). RESULTS: We observed low blood content of both (125)I-avidin-MX35 and (211)At-B-PL(suc), indicating fast clearance. After sodium perchlorate blocking, the highest (211)At uptake was found in kidneys. Red bone marrow (RBM) accumulated some (211)At activity. Mean absorbed doses of special interest were 2.3 Gy/MBq for kidneys, 0.4 Gy/MBq for blood, and 0.9 Gy/MBq for RBM. An absorbed dose of 0.9 Gy to the RBM was found to be safe. These values suggested that RBM would be the key dose-limiting organ in the proposed pretargeting scheme, and that blood data alone was not sufficient for predicting its absorbed dose. CONCLUSIONS: To attain a favorable distribution of activity and avoid major toxicities, at least 1.0 MBq of (211)At-B-PL(suc) can be administered 24 hours after an i.p. injection of avidin-MX35. These results provide a basis for future i.p. therapy studies in mice of microscopic ovarian cancer. PMID- 22087607 TI - Radioprotective effect of Ocimum sanctum and amifostine on the salivary gland of rats after therapeutic radioiodine exposure. AB - The current study investigated the radioprotective effect of Ocimum sanctum on the salivary gland of rats administered radioiodine ((131)I) and compared its efficacy with a known radioprotectant, amifostine. The experimental rats were divided in four groups and sacrificed in three different batches at 1, 3, and 6 months of time interval after 18.5 MBq/100g (i.p.) (131)I exposure. Six months duration batch received (131)I exposure twice with the gap of 3 months. Two groups of experimental rats were presupplemented with O. sanctum (40 mg/kg for 5 days, orally) and amifostine (200 mg/kg, s.c) before (131)I exposure separately. Increased Technetium-99m-pertechnetate ((99m)TcO(4)(-)) uptake at 30 minutes post injection in salivary glands of only (131)I exposed rats may imply delay in clearance at 6 months of exposure in comparison to their counterparts sacrificed at 1 month. Parotid gland histology showed atrophy with lipomatosis in only (131)I exposed rats at 3 and 6 months of duration. O. sanctum and amifostine presupplemented and subsequently exposed to (131)I rats at 3 and 6 months duration exhibited comparable histopathology with controls. Our study indicates possible radioprotective effect of O. sanctum and amifostine against high-dose (131)I exposure. PMID- 22087609 TI - Varicella-zoster virus prophylaxis with the traditional Chinese medicine Radix isatidis (Banlangen) in patients with multiple myeloma treated with bortezomib. PMID- 22087608 TI - Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure. AB - AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (-9.4 mmHg/min per litre and -14.7 mmHg/min per litre), mean arterial pressure (-2.8 mmHg and -8.4 mmHg) and LAP (left atrial pressure; -2.6 mmHg and -5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7 fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF. PMID- 22087610 TI - Amulets and other uncommon treatments prescribed by traditional medicinal practitioners of the Bede community residing in Porabari village of Dhaka district, Bangladesh. PMID- 22087611 TI - What is Bowenwork(r)? A systematic review. AB - OBJECTIVES: The objectives of this study were to systematically review the literature available on the complementary approach to healing known as Bowenwork((r)) and to examine reported research methods. METHODS: To the authors' knowledge, an exhaustive search of the computerized databases from the known scientific community on all available published literature on Bowenwork((r)) was conducted. Databases included Medline Ovid, PubMed, PsychINFO, and CINAHL((r)). The literature search included English language studies (1985-September 5, 2009) using the following search terms: Bowen Technique, Bowen Therapy, Bowtech, and Bowenwork((r)). In addition, a hand search of individual journals noted to publish complementary and alternative medicine articles was done (1997-2009). Abstracts of all studies were reviewed. Studies were included if (1) they referenced the original Bowenwork, (2) provided health-related outcomes, and (3) provided quantitative or qualitative data. Excluded articles included testimonials, duplicates, unrelated topics, literature reviews, articles lacking verifiable sources, and studies from proprietary resources. RESULTS: Of the 309 citations obtained, only 15 articles met the inclusion criteria (randomized clinical trial, n=1; quasi-experimental, n=2; mixed methods, n=3; cross sectional, n=2; case study, n=7). Over half of these studies (53%) reported that Bowenwork was effective for pain reduction and 33% reported improved mobility. In addition, several studies (n=5) reported the effectiveness of Bowenwork((r)) on the relief of symptoms experienced by persons living with a chronic illness, such as multiple sclerosis. CONCLUSIONS: Bowenwork((r)) may provide a noninvasive and affordable complementary approach to improvements in health. This intervention may offer improvements in pain reduction for various conditions such as frozen shoulder and migraines. While Bowenwork is recognized internationally, scientific evidence is not well documented. Further research is needed to systematically test this modality, before widespread recommendations can be given. PMID- 22087612 TI - Investigation of the delayed neuronal effects of acupuncture manipulations. AB - OBJECTIVES: The aim of this study was to investigate the delayed neuronal effects of acupuncture manipulations by observing blood oxygen level-dependent (BOLD) signal intensities. SUBJECTS: Fifteen (15) healthy, acupuncture-naive, right handed subjects (all males; mean age, 23 years; range, 21-24 years) participated in this study. DESIGN AND INTERVENTIONS: Each subject was scanned in eight sessions that consisted of two repeated baseline scans (Period 1), two repeated scans with acupuncture stimulation at right LR2 (Period 2), two repeated scans with retention (Period 3), and two repeated scans after removal of the needle (Period 4). OUTCOME MEASURES: Sixteen (16) regions of interest (ROI) were defined. The BOLD signals for each session were obtained for each ROI. A mixed effects analysis of variance (ANOVA) test was performed in order to investigate the BOLD signal differences of the Periods in the 16 ROIs. RESULTS: The BOLD signal intensities increased in Periods 2 and 3, and then started to decrease in Period 4 in the right amygdala, supramarginal gyrus, temporal pole, and superior temporal gyrus. However, the BOLD signal intensity in Period 4 was significantly higher than that of Period 1. Especially, BOLD signal intensity was elevated promptly in the insula and the parahippocampal gyrus, whereas it was persistently elevated (delayed effect) in the amygdala. CONCLUSIONS: BOLD signals were persistently elevated for at least 8 minutes after removal of the acupuncture needle or for at least 19 minutes after rotation of an acupuncture needle in some specific brain areas previously linked with LR2. In those specific brain ROIs, neuronal activation accompanying and following acupuncture showed both prompt and delayed effects. PMID- 22087613 TI - Management of distress during climacteric years by homeopathic therapy. AB - OBJECTIVES: The purpose of this study was to ascertain the usefulness of homeopathic therapy in the management of distressing symptoms encountered during climacteric years in women (primary objective) and also the changes brought about in the levels of follicle-stimulating hormone (FSH) and lipid profile in these women after homeopathic treatment (secondary objective). MATERIALS AND METHODS: An open, multicenter, prospective, observational study was carried out to ascertain the usefulness of homeopathic treatment in distress during climacteric years (DDCY). Patients were enrolled from the general outpatient department of the six Institutes/Units of Central Council for Research in Homoeopathy (CCRH) and were required to complete a follow-up period of 1 year as per the protocol designed by the CCRH. A uniform questionnaire assessing 15 predefined symptoms of menopause was adopted, with assessment of each symptom at every visit. Levels of serum FSH and lipid profile were monitored at entry and at completion. Effect size of the study was also calculated. CARA Software was used for repertorization of the presenting symptoms of menopause along with the characteristic attributes of each patient to arrive at a simillimum. The selected medicine was prescribed in a single dose as per the homeopathic principles. The assessment of the results was made through statistical analysis using the Wilcoxon signed rank test on Statistical Package for Social Sciences (SPSS) comparing symptom score at entry and completion of 1 year of treatment and t test for analyzing improvement in laboratory findings. RESULTS: Homeopathic therapy was found to be useful in relieving menopausal distressing symptoms such as hot flashes, night sweats, anxiety, palpitation, depression, insomnia, and so on. Influence on serum levels of FSH, high-density lipoprotein, and low-density lipoprotein was not significant but serum levels of cholesterol, triglycerides, and very-low-density lipoprotein decreased significantly. Effect size of the study was found to be large. The medicines found to be most frequently indicated and useful were Sepia, Lachesis, Calcarea carb., Lycopodium, and Sulphur. CONCLUSIONS: This study proves the usefulness of homeopathic medicines in relieving DDCY. PMID- 22087614 TI - A pilot study of website information regarding aromatase inhibitors: dietary supplement interactions. AB - OBJECTIVES: Patients who have hormone receptor-positive breast cancer and who are taking aromatase inhibitors (AIs) should understand the benefits and risks of concomitant dietary supplement (DS) use. The International Society for Integrative Oncology (SIO) encourages patients to discuss DS use with their health care practitioners. The objective was to conduct a pilot study rating Internet websites from the perspective of health care practitioners for information about AI-DS interactions. DESIGN: Five (5) Internet websites suggested by SIO were evaluated using the DISCERN instrument rating tool. The available AI-DS information on these websites was rated by 4 evaluators: 2 naturopathic doctors, 1 oncology pharmacy resident, and a pharmacy student. RESULTS: The overall rankings ranged from 1.6 to 3.9, with considerable variability in the type of information available from the websites. The interevaluator rankings of the websites ranged from 0.44 to 0.89. The evaluators consistently found the most reliable, unbiased, and comprehensive information on AI-DS interactions at the Natural Medicines Comprehensive Database and Memorial Sloan-Kettering Cancer Center websites. However, more than one database was needed for provision of optimal patient information on AI-DS interactions. CONCLUSIONS: In order to effectively advise patients regarding AI-DS interactions, more than one website should be evaluated to assess the potential efficacy and safety of DS in women whose breast cancer is being treated with an AI. PMID- 22087616 TI - Pulmonary functions of children with asthma improve following massage therapy. AB - OBJECTIVES: This study aimed at evaluating the effect of massage therapy on the pulmonary functions of stable Egyptian children with asthma. DESIGN: This study was an open, randomized, controlled trial. SETTINGS/LOCATION: The study was conducted in pediatric allergy and chest unit of the New Children's Hospital of Cairo University, Egypt. SUBJECTS AND INTERVENTIONS: Sixty (60) children with asthma were divided randomly into two equal groups: massage therapy group and control group. Subjects in the massage therapy group received a 20-minute massage therapy by their parents at home before bedtime every night for 5 weeks in addition to the standard asthma treatment. The control group received the standard asthma treatment alone for 5 weeks. OUTCOME MEASURES: Spirometry was performed for all children on the first and last days of the study. Forced expiratory flow in first second (FEV1), forced vital capacity (FVC), FEV1/FVC and peak expiratory flow (PEF) were recorded. RESULTS: At the end of the study, mean FEV1 of the massage therapy group was significantly higher than controls (2.3-0.8 L versus 1.9-0.9 L, p=0.04). There was no significant difference in FVC (2.5-0.8 L versus 2.7-0.7 L, p=0.43). However, FEV1/FVC ratio showed a significant improvement in the massage therapy group (92.3-21.5 versus 69.5-17, p<0.01). PEF difference was not significant (263.5-39.6 L/minute versus 245.9-32 L/minute, p=0.06). CONCLUSIONS: A beneficial role for massage therapy in pediatric asthma is suggested. It improved the key pulmonary functions of the children, namely, FEV1 and FEV1/FVC ratio. However, further research on a larger scale is warranted. PMID- 22087615 TI - A randomized, double-blinded, placebo-controlled study of the effect of a combination of lemon verbena extract and fish oil omega-3 fatty acid on joint management. AB - OBJECTIVES: The aim of this study was to test the efficacy of an antioxidant/anti inflammatory supplement containing standardized lemon verbena (Aloysia triphylla, Lippia citriodora) extract and fish oil omega-3 fatty acid in a human pilot trial as an alternative treatment for joint management. METHODS AND DESIGN: First, antioxidant activity of the supplement was determined through an oxygen radical absorbance capacity (ORAC) assay. In a randomized, double-blinded placebo controlled trial, 45 subjects with pain discomfort received the nutritional supplement or placebo for 9 weeks. Western Ontario MacMaster (WOMAC) and Lequesne's questionnaires, which are disease-specific measurements validated to measure joint dysfunction and pain, were administered and evaluated once per week in the placebo and intervention groups. OUTCOME MEASURES: Pain and stiffness symptoms, and joint function were determined once per week through recording their respective WOMAC and Lequesne's scores in the placebo and intervention groups. Statistically significant differences were determined at every measurement point between the two groups. RESULTS: Lemon verbena extract showed strong antioxidant properties as measured by the ORAC assay. The nutritional supplement containing standardized lemon verbena extract (14% verbascoside, w/w) and fish oil omega-3 fatty acid reduced symptoms of pain and stiffness significantly, and improved physical function as shown by WOMAC and Lequesne's scores after 9 weeks of treatment. WOMAC and Lequesne's total scores decreased 53% and 78%, respectively, at the end of the study compared to initial conditions. Onset of the effect was observed at the third and fourth weeks, when statistically significant differences were detected, compared to placebo. CONCLUSIONS: This pilot study reveals that supplementation with lemon verbena combined with omega-3 fatty acids may be considered for further investigation as a complementary and alternative treatment for improving joint status in subjects with joint discomfort. PMID- 22087617 TI - Five keys to real transformation in health care. AB - Transformation in health care requires a deeply holistic approach. Natural leaders of such a transformation are the complementary and alternative medicine practitioners who already share a vision of wellness, prevention, and optimal human function. Central to this shared vision is lifestyle change for patients and practitioners. Yet, to change a lifestyle is to change a self. Assisting individuals to transform their very sense of self in order to live healthier, more fulfilling lives centered on flourishing requires several important keys. Visionary and unified leaders are the first key. Structural support through coordination of health clinics locally and nationally is the second key. This can be optimized by utilizing initiatives of the new Affordable Health Care Act, because it provides a potential impetus for deep structural changes. An expanded evidence base for multifactorial approaches to wellness lifestyles is the third key. A reorganizational orientation with an emphasis on the right timing of transformation is the fourth key. The fifth key is an Integral map, which brings together the personal, behavioral, cultural, and social domains. By utilizing such a map, one ensures that no aspect of the transformative revolution at hand slips away due to any misplaced focus, such as emphasizing only on the things we can see with our eyes. By embracing the essence of transformation in terms of a wholeness to all reality, an evolutionary unifying field with interior depth and exterior expression, health care is redefined more authentically. PMID- 22087618 TI - Eribulin mesylate for the treatment of late-stage breast cancer. AB - INTRODUCTION: Chemotherapy agents, particularly anthracycline and taxane, have demonstrated their significance in metastatic breast cancer. However, improving overall survival in late-stage breast cancer remains a challenge. Eribulin mesylate, a new chemotherapy agent, has a proven significance in this setting. Eribulin mesylate is a synthetic analog of a macrolide isolated from a marine sponge. It inhibits microtubule polymerization, inducing mitosis arrest and apoptosis, and aggregates soluble tubulin in nonproductive form. In Phase II studies, this drug has shown a partial and stable response. The Phase III EMBRACE study showed that eribulin mesylate improved overall survival, compared with the physician's choice of treatment, in women who had received two to five prior chemotherapy regimens, including anthracycline and taxane for advanced breast cancer (median overall survival: 13.1 versus 10.6 months HR 0.81, p = 0.041). This compound is well tolerated. The most common adverse event is neutropenia. AREAS COVERED: This paper provides an introduction to the drug, eribulin mesylate, along with an overview of the current drug market for late-stage breast cancer; it also reviews its pharmacodynamics, pharmacokinetics and clinical efficacy. EXPERT OPINION: Currently, eribulin mesylate is only the third single agent chemotherapy that has improved overall survival (after anthracycline and taxane) in advanced breast cancer. These results, particularly in heavily pretreated breast cancer, suggest that this drug could become a new standard in the treatment of metastatic breast cancer, and should, therefore, be further developed in its earlier stages. PMID- 22087619 TI - Frank wallace notestein (1902-1983). AB - Abstract Frank W. Notestein, one of the architects of modern demography, died on 18 February 1983, after a long struggle with emphysema. President Emeritus of the Population Council, and former Professor of Demography at Princeton University, he had been living in retirement in Newtown, Pennsylvania, with his wife of fifty-six years, nee Daphne Limbach. PMID- 22087620 TI - Fertility exposure analysis: A new method for assessing the contribution of proximate determinants to fertility differentials. AB - Summary Several recent papers have dealt with the problem of assessing the impact of the proximate determinants on fertility. All these approaches rely on combining a series of separately estimated aggregate level indicators. This paper proposes an approach which uses individual-level data and thus permits regression analyses as well as analyses for sub-groups. In the course of development it became clear that there are several deficiencies and inconsistencies in the measurement and formation of indices proposed elsewhere, which are overcome. We illustrate our approach with data from the Dominican Republic. The approach used involves attributing exposure to one or more of several states, including pregnancy, lactational and non-lactational components of post-partum amenorrhoea, absence of sexual relations and contraception. Key elements are efficacies of contraception and components of post-partum infecundity and the treatment of overlaps through an explicit hierarchy. We treat both unconditional (or additive) and conditional analyses. Intriguing findings on the age-specific pattern of fertility control emerge. Major advantages of regression analysis, such as simultaneous treatment of several variables and estimation of sampling variation are stressed. PMID- 22087621 TI - The influence of child spacing on child survival. AB - Summary This study evaluates the strength of the influence of spacing on child survival. Data related to a traditional culture (Punjab) in which almost all children are breast-fed up to the age of 17 months. An initial pregnancy history survey, subsequent four years updating through continuous monitoring of vital events and a second cross-sectional pregnancy history survey at the mid-point provided a file containing information on pregnancies and survival of children of 5,018 women. The analysis first looks at the correlation between the lengths of the preceding and subsequent intervals of index children, then examines whether this correlation was related to the repeated pattern of child death or survival. Next, the influence of the duration of the preceding interval on the survival of the index child in general and after accounting for the fate of the preceding child were considered. Then the influence of the length of the subsequent interval on the survival of the index child after conception and after the birth of the next child were studied. Lastly, regression analyses with preceding and subsequent intervals as independent variables and age-specific survival or death as the dependent variable were performed. PMID- 22087622 TI - Old age and the demographic transition. AB - Summary This paper examines the impact of the demographic transition upon the potential supply of, and demand for, family support for the aged in Australia. Using census and survey information on population cohorts entering old age, comparisons are drawn concerning their surviving issue, household composition and family membership. Long-term changes in fertility are shown to have had only a small impact upon the supply of potential carers among relatives and, although the demographic transition has led to a more universal inclusion of old people in family networks, there have not been major changes through time in the proportions living in extended family households. Short-term changes, however, such as low fertility during the 1930s, have caused disordered cohort flow, with the result that current generations of the elderly are members of deprived cohorts in terms of their access to family support. PMID- 22087623 TI - Estimating the incidence of widow and widower re-marriages in India from census data. AB - Summary In this paper we develop a method for estimating the incidence of widow and widower re-marriages from the current marital status data given in a census or survey. The method basically consists of reversing the procedure of estimating adult mortality from information on widowhood status. The method is applied to the all-India data from the Census of 1971. The principal result is that about one-third of the ever widowed women and slightly fewer than two-thirds of the ever widowed men were currently remarried in 1971. Similar application of the method to earlier censuses, and to state-level data, may provide answers to some of the riddles in Indian sociology. PMID- 22087624 TI - The variance of population characteristics in stable populations, with applications to the distribution of income. AB - Summary Stable population theory has recently been used to analyse the effects of changes in fertility and mortality on economic variables such as income per head. In this paper more general results are derived to describe the effects of changing vital rates on the variance and higher moments of the distribution of some age-dependent variable. Simple analytical expressions are derived which decompose the effects of changes in age structure into the effects on inter cohort and intra-cohort variance. The results are easily applied to standard measures of the distribution of income. By combining the analytical results with actual age profiles of income and income variance from the United States and Brazil it is observed that both the magnitude and direction of the effects of population growth on measured inequality are sensitive to the specific age profiles used. The most surprising result is that the Brazilian age profiles suggest that higher growth rates may actually reduce measured inequality, although the effect is relatively small. PMID- 22087625 TI - Household structure and the tempo of family formation in comparative perspective. AB - Summary Previous research on the relationship between extended family residence and fertility has produced conflicting findings. In the present paper, we avoid a major shortcoming of past work by focusing on residence and fertility at a given stage of the life-cycle, i.e. the stage following first marriage. Results show that residence with husband's parents reduces age at marriage. Residence with wife's parents shows no such consistent effect. No evidence was found to support the claim that extended family residence consistently affects the length of the interval between marriage and the first birth. These findings are consistent across four cultural/ethnic groups. PMID- 22087626 TI - Fertility adaptation by rural-urban migrants in developing countries: The case of Korea. AB - Summary The purpose of this study is to develop and test a model to assess the influence of rural-urban migration on fertility in less developed countries. Two major reasons may account for lower fertility levels observed among such migrants than among women who remained in rural areas: a selection effect, and adaptation to constraints in the area of destination. Results of previous studies have only rarely suggested that the effect of adaptation was significant. We use the detailed personal migration and pregnancy histories recorded in the Korean World Fertility Survey of 1974 and an autoregressive model to control for unobservable variations in personal preferences for different family sizes between migrants and non-migrants. Our study provides evidence that adaptation following rural urban migration is a significant factor which explains the lower fertility of rural-urban migrants compared with that of rural stayers. PMID- 22087629 TI - Facing a "slow-motion disaster"--the UN meeting on noncommunicable diseases. PMID- 22087630 TI - Preparation of highly exfoliated polyester-clay nanocomposites: process-property correlations. AB - A large number of polyester nanocomposite batches featuring different kinds of nanoclay surface modifiers and up to 6 wt % nanoclay were manufactured using a solvent-based technique. Montmorillonite platelets modified with ammonium ions of different chemical architectures were examined to study the effect of ammonium ions on the extent of surface reactions with long-chain fatty acids. The ammonium montmorillonite was first dispersed and suspended in acetone. This suspension was further esterificated with dotriacontanoic (lacceroic) acid to form high density brushes on the clay surface. This led to achieving higher basal plane spacing of the montmorillonite platelets due to the reduction of electrostatic interactions holding them. The outcome of the surface esterification was analyzed by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The esterificated ammonium-modified clays were then mixed by five different mixing strategies based on the use of a three-roll mill mixer (TRM) and/or ultrasonication (US) to obtain the desired polyester-nanoclay dispersion, intercalation, and exfoliation. The dispersion states of the modified nanoclay in polymer were characterized from XRD, scanning electron microscopy (SEM), and low and high magnification transmission electron microscopy (TEM). Mechanical, thermal, and barrier properties of the resulting composites were experimentally characterized. The Mori-Tanaka method along with an orientation distribution function was used to verify the experimental effective stiffness of the polyester nanocomposite systems. The aspect ratio of nanoclays and their level of intercalation and/or exfoliation after mixing were also confirmed by the comparison of the experimental diffusivity results with those of Fick's diffusion model. Systems having 4 and 6 wt % esterificated ammonium nanoclay and prepared according to a combined TRM/US mixing procedure showed optimal performance with balanced properties and processing ease, thereby showing potential for use in the automotive, transportation, and packaging industries. PMID- 22087631 TI - Coercion within Danish psychiatry compared with 10 other European countries. AB - BACKGROUND: In 2008, the European Committee for the Prevention of Torture and Inhuman or Degrading Treatment or Punishment (CPT) criticized the use of mechanical restraint in Denmark and referred to it as ill-treatment. What do other European countries do better? To answer this question, we compared the use of coercive measures regarding psychiatric inpatients in Denmark and comparable European countries. AIMS: Comparing coercive measures from Denmark, Sweden, Norway, Finland, Iceland, Belgium, The Netherlands, United Kingdom, Ireland, France and Italy. METHODS: Review of international literature and a cross sectional study performed as a questionnaire survey. RESULTS: Denmark used more mechanical restraint and holding than Finland and Norway; however Sweden used twice as much as Denmark. Finland used more seclusion than did the other countries. Norway was the country that used the smallest amount of physical coercion. Only Norway, Finland, Sweden and Denmark had comparable representative data on coercion. CONCLUSIONS: Norway used less physical restraint than Denmark. We could not find any obvious reasons for the differences in the use of physical restraint. CLINICAL IMPLICATIONS: Comparing the factors surrounding coercion between countries may serve as a basis for minimizing coercion and carrying it out in the most acceptable manner for the patients, thereby providing better psychiatric treatment in Europe. PMID- 22087633 TI - Direct functionalization of M-C (M = Pt(II), Pd(II)) bonds using environmentally benign oxidants, O2 and H2O2. AB - Atom economy and the use of "green" reagents in organic oxidation, including oxidation of hydrocarbons, remain challenges for organic synthesis. Solutions to this problem would lead to a more sustainable economy because of improved access to energy resources such as natural gas. Although natural gas is still abundant, about a third of methane extracted in distant oil fields currently cannot be used as a chemical feedstock because of a dearth of economically and ecologically viable methodologies for partial methane oxidation. Two readily available "atom economical" "green" oxidants are dioxygen and hydrogen peroxide, but few methodologies have utilized these oxidants effectively in selective organic transformations. Hydrocarbon oxidation and C-H functionalization reactions rely on Pd(II) and Pt(II) complexes. These reagents have practical advantages because they can tolerate moisture and atmospheric oxygen. But this tolerance for atmospheric oxygen also makes it challenging to develop novel organometallic palladium and platinum-catalyzed C-H oxidation reactions utilizing O(2) or H(2)O(2). This Account focuses on these challenges: the development of M-C bond (M = Pt(II), Pd(II)) functionalization and related selective hydrocarbon C-H oxidations with O(2) or H(2)O(2). Reactions discussed in this Account do not involve mediators, since the latter can impart low reaction selectivity and catalyst instability. As an efficient solution to the problem of direct M-C oxidation and functionalization with O(2) and H(2)O(2), this Account introduces the use of facially chelating semilabile ligands such as di(2 pyridyl)methanesulfonate and the hydrated form of di(2-pyridyl)ketone that enable selective and facile M(II)-C(sp(n)) bond functionalization with O(2) (M = Pt, n = 3; M = Pd, n = 3 (benzylic)) or H(2)O(2) (M = Pd, n = 2). The reactions proceed efficiently in protic solvents such as water, methanol, or acetic acid. With the exception of benzylic Pd(II) complexes, the organometallic substrates studied form isolable high-valent Pt(IV) or Pd(IV) intermediates as a result of an oxidant attack at the M(II) atom. The resulting high-valent M(IV) intermediates undergo C-O reductive elimination, leading to products in high yields. Guidelines for the synthesis of products containing other C-X bonds (X = OAc, Cl, Br) while using O(2) or H(2)O(2) as oxidants are also discussed. Although the M(II)-C bond functionalization reactions including high-valent intermediates are well understood, the mechanism for the aerobic functionalization of benzylic Pd(II) complexes will require a more detailed exploration. Importantly, further optimization of the systems suitable for stoichiometric M(II)-C bond functionalization led to the development of catalytic reactions, including selective acetoxylation of benzylic C-H bonds with O(2) as the oxidant and hydroxylation of aromatic C-H bonds with H(2)O(2) in acetic acid solutions. Both reactions proceed efficiently with substrates that contain a directing heteroatom. This Account also describes catalytic methods for ethylene dioxygenation with H(2)O(2) using M(II) complexes supported by facially chelating ligands. Mechanistic studies of these new oxidation reactions point to important ways to improve their substrate scope and to develop "green" CH functionalization chemistry. PMID- 22087632 TI - Increasing safer sexual behavior among Lao kathoy through an integrated social marketing approach. AB - BACKGROUND: Although HIV prevalence has remained low in Laos thus far, there is reason to be concerned that Lao male-to-female (MtF) transgender persons (kathoy) and their partners may facilitate the spread of HIV. Little is known about how to most effectively reach kathoy with HIV prevention programming. This paper evaluates an intervention with Lao kathoy with the objective of increasing safe sex with regular and casual partners. METHODS: Quantitative surveys were administered in November 2004 (n = 288) and June 2006 (n = 415) using time location sampling at venues where kathoy were known to congregate. Respondents were aged 15-35 and from three urban centers in Laos. UNIANOVA tests were used to compare baseline and follow-up survey data and to evaluate the impact of PSI's kathoy-specific interventions on items that changed significantly over time. RESULTS: Exposure to the intervention was associated with higher levels of condom use at last anal sex with casual partners and greater use of water-based lubricant. Exposure was also linked to improved perceptions of product availability for condoms and water-based lubricant. Knowledge about the importance of consistent condom use improved over time as well as the need to use condoms with regular partners. Some HIV knowledge decreased over time and the intention to use condoms with casual partners when water-based lubricant is available also declined. CONCLUSIONS: Study results demonstrate the feasibility of reaching kathoy with an integrated social marketing approach; combining product promotion, peer education, and other types of interpersonal communication. The approach was successful at increasing condom use with casual partners and water-based lubricant use, but the importance of using condoms along with water-based lubricant must be emphasized and modified strategies are required for improving condom use with boyfriends. Future messages should emphasize consistent condom use with all types of partners as well as improve knowledge and correct misconceptions about HIV and AIDS, STIs, condom use, and lubricant use. It is also important that authorities create an enabling environment to support such interventions and help foster behavior change. PMID- 22087634 TI - Molecular hydrogen tweezers: structure and mechanisms by neutron diffraction, NMR, and deuterium labeling studies in solid and solution. AB - The mechanism of reversible hydrogen activation by ansa-aminoboranes, 1-N-TMPH CH(2)-2-[HB(C(6)F(5))(2)]C(6)H(4) (NHHB), was studied by neutron diffraction and thermogravimetric mass-spectroscopic experiments in the solid state as well as with NMR and FT-IR spectroscopy in solution. The structure of the ansa-ammonium borate NHHB was determined by neutron scattering, revealing a short N-H...H-B dihydrogen bond of 1.67 A. Moreover, this intramolecular H-H distance was determined in solution to be also 1.6-1.8 A by (1)H NMR spectroscopic T(1) relaxation and 1D NOE measurements. The X-ray B-H and N-H distances deviated from the neutron and the calculated values. The dynamic nature of the molecular tweezers in solution was additionally studied by multinuclear and variable temperature NMR spectroscopy. We synthesized stable, individual isotopic isomers NDDB, NHDB, and NDHB. NMR measurements revealed a primary isotope effect in the chemical shift difference (p)Delta(1)H(D) = delta(NH) - delta(ND) (0.56 ppm), and hence supported dihydrogen bonding. The NMR studies gave strong evidence that the structure of NHHB in solution is similar to that in the solid state. This is corroborated by IR studies providing clear evidence for the dynamic nature of the intramolecular dihydrogen bonding at room temperature. Interestingly, no kinetic isotope effect was detected for the activation of deuterium hydride by the ansa aminoborane NB. Theoretical calculations attribute this to an "early transition state". Moreover, 2D NOESY NMR measurements support fast intermolecular proton exchange in aprotic CD(2)Cl(2) and C(6)D(6). PMID- 22087635 TI - Facile O-H bond activation in alcohols by [Cp*RuCl((I)Pr2PSX)] (X = pyridyl, quinolyl): a route to ruthenium(IV) hydrido(alkoxo) derivatives. AB - The complexes [Cp*RuCl((i)Pr(2)PSX)] (X = pyridyl, quinolyl) react directly with alcohols ROH (R = Me, Et, (i)Pr, (n)Pr) and NaBPh(4), affording the novel cationic hydrido(alkoxo) derivatives [Cp*RuH(OR)((i)Pr(2)PSX)][BPh(4)]. These ruthenium(IV) compounds result from the formal oxidative addition of the alcohol to the 16-electron fragment {[Cp*Ru((i)Pr(2)PSX)](+)}, generated in situ upon chloride dissociation. The hydrido(alkoxo) complexes are reversibly deprotonated by a strong base such as KOBu(t), yielding the neutral alkoxides [Cp*Ru(OR)((i)Pr(2)PSX)], which are remarkably stable toward beta elimination and do not generate the corresponding hydrides. The hydrido(alkoxo) complexes undergo a slow electron-transfer process, releasing H(2) and generating the dinuclear ruthenium(III) complex [{Cp*Ru(kappa(2)-N,S-MU S-SC(5)H(4)N)}(2)][BPh(4)](2). In this species, the Ru-Ru separation is very short and consistent with what is expected for a Ru=Ru triple bond. PMID- 22087636 TI - Six alkaloids inhibit secretion of IL-1alpha, TXB(2), ET-1 and E-selectin in LPS induced endothelial cells. AB - The aim of the research was to investigate the antiendotoxin effects of Sinomenine, Fangchinoline, Stachydrine, Chuanxionggzine, Oxymartrine and Evodiamine. Endothelial cells were challenged with 1 MUg/mL LPS for 3 h then treated respectively with six alkaloids at three concentrations (1, 5 and 10 MUg/mL). The cells were incubated at 37 degrees C in a cell incubator for 21 h. The supernatants were collected and analyzed the levels of interleukin-1alpha (IL 1alpha), thromboxane B(2) (TXB(2)), endothelin-1 (ET-1) and E-selectin by ELISA kits. The results revealed that Sinomenine, Oxymartrine and Evodiamine inhibited the production of IL-1alpha; Stachydrine, Chuanxionggzine and Evodiamine inhibited the secretion of TXB(2); Sinomenine and Oxymartrine down-regulated ET-1 expression; Fangchinoline and Evodiamine decreased the level of E-selectin. All these changes were significant. Taken together, the data suggested that six alkaloids may effectively reduce inflammatory response via these cytokines. PMID- 22087637 TI - Low incidence of paradoxical reductions in HDL-C levels in dyslipidemic patients treated with fenofibrate alone or in combination with ezetimibe or ezetimibe/simvastatin. AB - BACKGROUND: Fibrates have been reported to cause paradoxical decreases in HDL-C in certain patients. DESIGN AND METHODS: This post-hoc analysis explored the frequency/magnitude of HDL-C reductions in a pooled database of mixed dyslipidemic patients (LDL-C:3.4-5.7 mmol/L;TG:1.7-5.7 mmol/L) receiving placebo (PBO), fenofibrate (FENO), ezetimibe plus FENO (EZE+FENO), or EZE/simvastatin plus FENO (EZE/SIMVA+FENO) for 12 weeks. RESULTS: PBO-treated patients had the highest incidence of HDL-C reductions from baseline (45%) compared with patients taking FENO (14%), EZE+FENO (9%), or EZE/SIMVA+FENO (9%). Reductions <30% reflected natural variability since the largest reduction in HDL-C approached 30% in the PBO group. Only 3 patients exhibited HDL-C reductions >=30% (i.e., 2 patients in the FENO group and 1 in the EZE+FENO group). There were no differences in demographic/biochemical characteristics between patients with and without HDL-C reductions. CONCLUSIONS: The incidence of paradoxical HDL-C reductions was low in mixed dyslipidemic patients receiving FENO alone or combined with EZE or EZE/SIMVA. PMID- 22087638 TI - Detection of IL-1beta in culture media supernatants of pre-implantation human embryos; its relation with embryo grades and development. AB - In this study, we aimed to determine whether human embryos secrete interleukin 1beta (IL-1beta) into culture media and its correlation with embryo grade and development. Culture media supernatants of 100 embryos obtained from 39 cycles of 38 patients and cultivated individually were collected 2 and 3 days after intracytoplasmic sperm injection (ICSI). IL-1beta concentrations of samples were determined with ELISA and compared with embryo grades and blastomere numbers. Embryo grades and the amount of IL-1beta they secreted were found not to be correlated (p:0.559). Numbers of blastomeres each embryo had at 2nd and 3rd days were found to be correlated with IL-1beta secreted (p:0.00 and p:0.00, respectively). Mean amount of IL-1beta secreted by the embryos from ejaculated sperm cycles were found to be significantly higher than that of embryos from TESE cycles (p:0.016). Patient age and etiology of infertility were not correlated with the amount of IL-1beta secreted and embryo grade. In conclusion, preimplantation human embryos secrete IL-1beta in their media in amounts correlated with their blastomere numbers. PMID- 22087639 TI - Hot spots and transient pockets: predicting the determinants of small-molecule binding to a protein-protein interface. AB - Protein-protein interfaces are considered difficult targets for small-molecule protein-protein interaction modulators (PPIMs ). Here, we present for the first time a computational strategy that simultaneously considers aspects of energetics and plasticity in the context of PPIM binding to a protein interface. The strategy aims at identifying the determinants of small-molecule binding, hot spots, and transient pockets, in a protein-protein interface in order to make use of this knowledge for predicting binding modes of and ranking PPIMs with respect to their affinity. When applied to interleukin-2 (IL-2), the computationally inexpensive constrained geometric simulation method FRODA outperforms molecular dynamics simulations in sampling hydrophobic transient pockets. We introduce the PPIAnalyzer approach for identifying transient pockets on the basis of geometrical criteria only. A sequence of docking to identified transient pockets, starting structure selection based on hot spot information, RMSD clustering and intermolecular docking energies, and MM-PBSA calculations allows one to enrich IL 2 PPIMs from a set of decoys and to discriminate between subgroups of IL-2 PPIMs with low and high affinity. Our strategy will be applicable in a prospective manner where nothing else than a protein-protein complex structure is known; hence, it can well be the first step in a structure-based endeavor to identify PPIMs. PMID- 22087640 TI - China needs forest management rather than reforestation for carbon sequestration. PMID- 22087641 TI - Quantum mechanical/molecular mechanical structure, enantioselectivity, and spectroscopy of hydroxyretinals and insights into the evolution of color vision in small white butterflies. AB - Since Vogt's discovery of A(3)-retinal or 3-hydroxyretinal in insects in 1983 and Matsui's discovery of A(4)-retinal or 4-hydroxyretinal in firefly squid in 1988, hydroxyretinal-protein interactions mediating vision have remained largely unexplored. In the present study, A(3)- and A(4)-retinals are theoretically incorporated into squid and bovine visual pigments by use of the hybrid quantum mechanics/molecular mechanics [SORCI+Q//B3LYP/6-31G(d):Amber96] method, and insights into structure, enantioselectivity, and spectroscopy are gathered and presented for the first time. Contrary to general perception, our findings rule out the formation of a hydrogen bond between the hydroxyl-bearing beta-ionone ring portion of retinal and opsin. Compared to A(1)-pigments, A(3)- and A(4) pigments exhibit slightly blue-shifted absorption maxima due to increase in bond length alternation of the hydroxyretinal. We suggest that (i) the binding site of firefly squid (Watasenia scintillans) opsin is very similar to that of the Japanese common squid (Todarodes pacificus) opsin; (ii) the molecular mechanism of spectral tuning in small white butterflies involve sites S116 and T185 and breaking of a hydrogen bond between sites E180 and T185; and finally (iii) A(3) retinal may have occurred during the conversion of A(1)- to A(2)-retinal and insects may have acquired them, in order to absorb light in the blue-green wavelength region and to speed up the G-protein signaling cascade. PMID- 22087642 TI - Amino triazolo diazepines (Ata) as constrained histidine mimics. AB - Two synthetic routes for the synthesis of amino-triazolodiazepine (Ata) scaffolds are presented. The scope of both of these proceeding through key intra- and intermolecular Huisgen cycloaddition reactions is discussed. The replacement of the His-Pro dipeptide segment in angiotensin IV by the dipeptide mimetic Ata-Gly and subsequent biological evaluation in two inhibitory enzyme assays validated the use of the Ata moiety as a His mimic given the equipotency of both peptidic analogs. PMID- 22087643 TI - Comment on benzene exposure ratio method. PMID- 22087644 TI - Exploring variables associated with change in cognitive behaviour therapy (CBT) for anxiety following traumatic brain injury. AB - PURPOSE: In a pilot randomized controlled trial, we investigated the effectiveness of a 12-weekly anxiety treatment programme adapted for individuals with moderate-severe TBI, based on cognitive behaviour therapy (CBT) and Motivational Interviewing (MI). The current study explored the variables associated with treatment response and group differences in change expectancy and working alliance. METHODS: Twenty-seven participants recruited from a brain injury rehabilitation hospital were randomly assigned to MI + CBT, non-directive counselling (NDC) + CBT and treatment-as-usual and assessors were blinded to treatment conditions. Correlation and multiple regression were used to examine the association between reduction in anxiety ratings and a number of clinical, injury and cognitive variables. Random effects regression was used to examine group difference in changes in working alliance and expectancy. RESULTS: There was a trend suggesting that greater injury severity may be predictive of poorer response to CBT and injury severity was significantly related to memory functioning. Participants receiving MI pre-treatment showed a greater increase in change expectancy at the end of CBT and at follow-up, but not at the end of MI. CONCLUSIONS: There is a need to further investigate the effectiveness of treatment for individuals with different injury severity and to explore the relationship between change expectancy and treatment outcome. PMID- 22087645 TI - High-risk HPV infection after five years in a population-based cohort of Chilean women. AB - BACKGROUND: The need to review cervical cancer prevention strategies has been triggered by the availability of new prevention tools linked to human papillomavirus (HPV): vaccines and screening tests. To consider these innovations, information on HPV type distribution and natural history is necessary. This is a five-year follow-up study of gynecological high-risk (HR) HPV infection among a Chilean population-based cohort of women. FINDINGS: A population-based random sample of 969 women from Santiago, Chile aged 17 years or older was enrolled in 2001 and revisited in 2006. At both visits they answered a survey on demographics and sexual history and provided a cervical sample for HPV DNA detection (GP5+/6+ primer-mediated PCR and Reverse line blot genotyping). Follow-up was completed by 576 (59.4%) women; 45 (4.6%) refused participation; most losses to follow-up were women who were unreachable, no longer eligible or had missing samples. HR-HPV prevalence increased by 43%. Incidence was highest in women < 20 years of age (19.4%) and lowest in women > 70 (0%); it was three times higher among women HR-HPV positive versus HPV negative at baseline (25.5% and 8.3%; OR 3.8, 95% CI 1.8-8.0). Type-specific persistence was 35.3%; it increased with age, from 0% in women < 30 years of age to 100% in women > 70. An enrollment Pap result ASCUS or worse was the only risk factor for being HR-HPV positive at both visits. CONCLUSIONS: HR-HPV prevalence increased in the study population. All HR-HPV infections in women < 30 years old cleared, supporting the current recommendation of HR-HPV screening for women > 30 years. PMID- 22087646 TI - Anodization of nanoporous alumina on impurity-induced hemisphere curved surface of aluminum at room temperature. AB - Nanoporous alumina which was produced by a conventional direct current anodization [DCA] process at low temperatures has received much attention in various applications such as nanomaterial synthesis, sensors, and photonics. In this article, we employed a newly developed hybrid pulse anodization [HPA] method to fabricate the nanoporous alumina on a flat and curved surface of an aluminum [Al] foil at room temperature [RT]. We fabricate the nanopores to grow on a hemisphere curved surface and characterize their behavior along the normal vectors of the hemisphere curve. In a conventional DCA approach, the structures of branched nanopores were grown on a photolithography-and-etched low-curvature curved surface with large interpore distances. However, a high-curvature hemisphere curved surface can be obtained by the HPA technique. Such a curved surface by HPA is intrinsically induced by the high-resistivity impurities in the aluminum foil and leads to branching and bending of nanopore growth via the electric field mechanism rather than the interpore distance in conventional approaches. It is noted that by the HPA technique, the Joule heat during the RT process has been significantly suppressed globally on the material, and nanopores have been grown along the normal vectors of a hemisphere curve. The curvature is much larger than that in other literatures due to different fabrication methods. In theory, the number of nanopores on the hemisphere surface is two times of the conventional flat plane, which is potentially useful for photocatalyst or other applications.PACS: 81.05.Rm; 81.07.-b; 82.45.Cc. PMID- 22087647 TI - Replicated associations of TNFAIP3, TNIP1 and ETS1 with systemic lupus erythematosus in a southwestern Chinese population. AB - INTRODUCTION: Recent genome-wide and candidate gene association studies in large numbers of systemic lupus erythematosus (SLE) patients have suggested approximately 30 susceptibility genes. These genes are involved in three types of biological processes, including immune complex processing, toll-like receptor function and type I interferon production, and immune signal transduction in lymphocytes, and they may contribute to the pathogenesis of SLE. To better understand the genetic risk factors of SLE, we investigated the associations of seven SLE susceptibility genes in a Chinese population, including FCGR3A, FCGR2A, TNFAIP3, TLR9, TREX1, ETS1 and TNIP1. METHODS: A total of 20 SNPs spanning the seven SLE susceptibility genes were genotyped in a sample of 564 unrelated SLE patients and 504 unrelated healthy controls recruited from Yunnan, southwestern China. The associations of SNPs with SLE were assessed by statistical analysis. RESULTS: Five SNPs in two genes (TNFAIP3 and ETS1) were significantly associated with SLE (corrected P values ranging from 0.03 to 5.5 * 10(-7)). Through stratified analysis, TNFAIP3 and ETS1 showed significant associations with multiple SLE subphenotypes (such as malar rash, arthritis, hematologic disorder and antinuclear antibody) while TNIP1 just showed relatively weak association with onset age. The associations of the SNPs in the other four genes were not replicated. CONCLUSIONS: The replication analysis indicates that TNFAIP3, ETS1 and TNIP1 are probably common susceptibility genes for SLE in Chinese populations, and they may contribute to the pathogenesis of multiple SLE subphenotypes. PMID- 22087648 TI - C2'-pyrene-functionalized triazole-linked DNA: universal DNA/RNA hybridization probes. AB - Development of universal hybridization probes, that is, oligonucleotides displaying identical affinity toward matched and mismatched DNA/RNA targets, has been a longstanding goal due to potential applications as degenerate PCR primers and microarray probes. The classic approach toward this end has been the use of "universal bases" that either are based on hydrogen-bonding purine derivatives or aromatic base analogues without hydrogen-bonding capabilities. However, development of probes that result in truly universal hybridization without compromising duplex thermostability has proven challenging. Here we have used the "click reaction" to synthesize four C2'-pyrene-functionalized triazole-linked 2' deoxyuridine phosphoramidites. We demonstrate that oligodeoxyribonucleotides modified with the corresponding monomers display (a) minimally decreased thermal affinity toward DNA/RNA complements relative to reference strands, (b) highly robust universal hybridization characteristics (average differences in thermal denaturation temperatures of matched vs mismatched duplexes involving monomer W are <1.7 degrees C), and (c) exceptional affinity toward DNA targets containing abasic sites opposite of the modification site (DeltaT(m) up to +25 degrees C). The latter observation, along with results from absorption and fluorescence spectroscopy, suggests that the pyrene moiety is intercalating into the duplex whereby the opposing nucleotide is pushed into an extrahelical position. These properties render C2'-pyrene-functionalized triazole-linked DNA as promising universal hybridization probes for applications in nucleic acid chemistry and biotechnology. PMID- 22087649 TI - The standardization of urine particle counting in medical laboratories--a Polish experience with the EQA programme. AB - BACKGROUND: Given the common problems with the standardization of urine particle counting methods and the great variability in the results obtained by Polish laboratories under international Labquality External Quality Assessment (EQA), we initiated educational recovery activities. METHODS: Detailed instructions on how to perform the standardized examination were sent to EQA participants, as was a questionnaire forms which enabled information to be gathered in respect to the procedures being applied. Laboratory results were grouped according to the method declared on the EQA 'Result' form or according to a manual examination procedure established on the basis of the questionnaire. The between-laboratory CVs for leukocyte and erythrocyte counts were calculated for each group and compared using the Mann-Whitney test. RESULTS: Significantly lower between-laboratory CVs (p = 0.03) were achieved for leukocyte counting among the laboratories that analysed control specimens in accordance with standardized procedures as compared with those which used non-standardized procedures. We also observed a visible lower variability for erythrocyte counting. Unfortunately despite our activities, only a few of the Polish laboratories applied the standardized examination procedures, and only 29% of the results could have been considered to be standardized (16% - manual methods, 13% - automated systems). CONCLUSIONS: The standardization of urine particle counting methods continues to be a significant problem in medical laboratories and requires further recovery activities which can be conducted using the EQA scheme. PMID- 22087650 TI - Delineation of the Pasteurellaceae-specific GbpA-family of glutathione-binding proteins. AB - BACKGROUND: The Gram-negative bacterium Haemophilus influenzae is a glutathione auxotroph and acquires the redox-active tripeptide by import. The dedicated glutathione transporter belongs to the ATP-binding cassette (ABC)-transporter superfamily and displays more than 60% overall sequence identity with the well studied dipeptide (Dpp) permease of Escherichia coli. The solute binding protein (SBP) that mediates glutathione transport in H. influenzae is a lipoprotein termed GbpA and is 54% identical to E. coli DppA, a well-studied member of family 5 SBP's. The discovery linking GbpA to glutathione import came rather unexpectedly as this import-priming SBP was previously annotated as a heme binding protein (HbpA), and was thought to mediate heme acquisition. Nonetheless, although many SBP's have been implicated in more than one function, a prominent physiological role for GbpA and its partner permease in heme acquisition appears to be very unlikely. Here, we sought to characterize five representative GbpA homologs in an effort to delineate the novel GbpA-family of glutathione-specific family 5 SBPs and to further clarify their functional role in terms of ligand preferences. RESULTS: Lipoprotein and non-lipoprotein GbpA homologs were expressed in soluble form and substrate specificity was evaluated via a number of ligand binding assays. A physiologically insignificant affinity for hemin was observed for all five GbpA homologous test proteins. Three out of five test proteins were found to bind glutathione and some of its physiologically relevant derivatives with low- or submicromolar affinity. None of the tested SBP family 5 allocrites interacted with the remaining two GbpA test proteins. Structure-based sequence alignments and phylogenetic analysis show that the two binding-inert GbpA homologs clearly form a separate phylogenetic cluster. To elucidate a structure-function rationale for this phylogenetic differentiation, we determined the crystal structure of one of the GbpA family outliers from H. parasuis. Comparisons thereof with the previously determined structure of GbpA in complex with oxidized glutathione reveals the structural basis for the lack of allocrite binding capacity, thereby explaining the outlier behavior. CONCLUSIONS: Taken together, our studies provide for the first time a collective functional look on a novel, Pasteurellaceae-specific, SBP subfamily of glutathione binding proteins, which we now term GbpA proteins. Our studies strongly implicate GbpA family SBPs in the priming step of ABC-transporter-mediated translocation of useful forms of glutathione across the inner membrane, and rule out a general role for GbpA proteins in heme acquisition. PMID- 22087651 TI - Transgenic analysis of the role of FKBP12.6 in cardiac function and intracellular calcium release. AB - FK506 binding protein12.6 (FKBP12.6) binds to the Ca(2+) release channel ryanodine receptor (RyR2) in cardiomyocytes and stabilizes RyR2 to prevent premature sarcoplasmic reticulum Ca(2+) release. Previously, two different mouse strains deficient in FKBP12.6 were reported to have different abnormal cardiac phenotypes. The first mutant strain displayed sex-dependent cardiac hypertrophy, while the second displayed exercise-induced cardiac arrhythmia and sudden death. In this study, we tested whether FKBP12.6-deficient mice that display hypertrophic hearts can develop exercise-induced cardiac sudden death and whether the hypertrophic heart is a direct consequence of abnormal calcium handling in mutant cardiomyocytes. Our data show that FKBP12.6-deficient mice with cardiac hypertrophy do not display exercise-induced arrhythmia and/or sudden cardiac death. To investigate the role of FKBP12.6 overexpression for cardiac function and cardiomyocyte calcium release, we generated a transgenic mouse line with cardiac specific overexpression of FKBP12.6 using alpha-myosin heavy chain (alphaMHC) promoter. MHC-FKBP12.6 mice displayed normal cardiac development and function. We demonstrated that MHC-FKBP12.6 mice are able to rescue abnormal cardiac hypertrophy and abnormal calcium release in FKBP12.6-deficient mice. PMID- 22087652 TI - Where are all the biomarkers? PMID- 22087653 TI - Combined proteomic technology in landmark study encourages advancement in personalized multiple myeloma treatment. PMID- 22087654 TI - Proteome profiling for the identification of lung cancer signatures. AB - Comprehensive and in-depth discovery of the disease proteome is an important issue in recent proteomics developments. Previous studies have shown a number of biomarkers discovered in various diseases, including lung cancer. Some of them are potentially useful in lung cancer diagnostics and prognostics. However, few of them can act as organ-specific biomarkers to extensively compare multiple cancer models. This article evaluates a recently published study employing comparative proteomics on multiple genetically engineered mouse models and sheds light on the usefulness and application of the discovered marker panel for human lung cancer diagnostics. PMID- 22087655 TI - Brain asymmetry: both sides of the story. AB - Biological systems demonstrate asymmetry, while lateralization has been observed from humans to lower animals structurally, functionally and behaviorally. This may be derived from evolutionary, genetic, developmental, epigenetic and pathologic factors. However, brain structure and function is complex, and macroscopic or microscopic asymmetries are hard to discern from random fluctuations. In this article, we discuss brain laterality and lateralization, beginning with a brief review of the literature on brain structural and functional asymmetries. We conclude with methods to detect and quantify asymmetry, focusing on neuroproteomics, for retrieval of protein-expression patterns, as a method of diagnosis and treatment monitoring. We suggest inter hemispheric differential proteomics as a valid method to assess the experimental and biological variations in the healthy brain, and neurologic and neuropsychiatric disorders. PMID- 22087657 TI - Proteomics of blood and derived products: what's next? AB - Proteomics has changed the way proteins are analyzed in living systems. This approach has been applied to blood products and protein profiling has evolved in parallel with the development of techniques. The identification of proteins belonging to red blood cell, platelets or plasma was achieved at the end of the last century. Then, the questions on the applications emerged. Hence, several studies have focused on problems related to blood banking and products, such as the aging of blood products, identification of biomarkers, related diseases and the protein-protein interactions. More recently, a mass spectrometry-based proteomics approach to quality control has been applied in order to offer solutions and improve the quality of blood products. The current challenge we face is developing a closer relationship between transfusion medicine and proteomics. In this article, these issues will be approached by focusing first on the proteome identification of blood products and then on the applications and future developments within the field of proteomics and blood products. PMID- 22087656 TI - Recent advances in biomarker discovery in solid organ transplant by proteomics. AB - The identification and clinical use of more sensitive and specific biomarkers in the field of solid organ transplantation is an urgent need in medicine. Solid organ transplantation has seen improvements in the short-term survival of transplanted organs due to recent advancements in immunosuppressive therapy. However, the currently available methods of allograft monitoring are not optimal. Recent advancements in assaying methods for biomolecules such as genes, mRNA and proteins have helped to identify surrogate biomarkers that can be used to monitor the transplanted organ. These high-throughput 'omic' methods can help researchers to significantly speed up the identification and the validation steps, which are crucial factors for biomarker discovery efforts. Still, the progress towards identifying more sensitive and specific biomarkers remains a great deal slower than expected. In this article, we have evaluated the current status of biomarker discovery using proteomics tools in different solid organ transplants in recent years. This article summarizes recent reports and current status, along with the hurdles in efficient biomarker discovery of protein biomarkers using proteomics approaches. Finally, we will touch upon personalized medicine as a future direction for better management of transplanted organs, and provide what we think could be a recipe for success in this field. PMID- 22087658 TI - Proteomic tools against the neglected pathology of snake bite envenoming. AB - This article covers the application of proteomic tools ('venomics', 'antivenomics' and 'venom phenotyping') to study the composition and natural history of snake venoms, and the cross-reactivity of antivenoms with homologous and heterologous venoms, to help address the neglected pathology of snake bite envenoming. The identification of evolutionary and immunological trends may help to replace the traditional geographic- and phylogenetic-driven hypotheses for antivenom production strategies with a more rational approach based on proteome phenotype and immunological profile similarities. Antivenomics and venom phenotyping may also contribute to expand the clinical range of currently existing antidotes. PMID- 22087659 TI - Mass spectrometry-based functional proteomics of poly(ADP-ribose) polymerase-1. AB - PARP-1 is an abundant nuclear protein that plays an essential role in the regulation of many genome integrity and chromatin-based processes, such as DNA repair, replication or transcriptional regulation. PARP-1 modulates the function of chromatin and nuclear proteins through several poly(ADP-ribose) (pADPr) dependent pathways. Aside from the clearly established role of PARP-1 in the maintenance of genome stability, PARP-1 also emerged as an important regulator that links chromatin functions with extranuclear compartments. pADPr signaling has notably been found to be responsible for PARP-1-mediated mitochondrial dysfunction and cell death. Defining the mechanisms that govern the intrinsic functions of PARP-1 is fundamental to the understanding of signaling networks regulated by pADPr. The emergence of mass spectrometry-based proteomics and its broad applications in the study of biological systems represents an outstanding opportunity to widen our knowledge of the functional spectrum of PARP-1. In this article, we summarize various PARP-1 targeted proteomics studies and proteome wide analyses that shed light on its protein interaction partners, expression levels and post-translational modifications. PMID- 22087660 TI - Dissecting phosphorylation networks: lessons learned from yeast. AB - Protein phosphorylation continues to be regarded as one of the most important post-translational modifications found in eukaryotes and has been implicated in key roles in the development of a number of human diseases. In order to elucidate roles for the 518 human kinases, phosphorylation has routinely been studied using the budding yeast Saccharomyces cerevisiae as a model system. In recent years, a number of technologies have emerged to globally map phosphorylation in yeast. In this article, we review these technologies and discuss how these phosphorylation mapping efforts have shed light on our understanding of kinase signaling pathways and eukaryotic proteomic networks in general. PMID- 22087661 TI - Intact proteome fractionation strategies compatible with mass spectrometry. AB - Proteome fractionation refers to separation at the level of intact proteins. Proteome fractionation may precede sample digestion and subsequent peptide-level separation and detection (i.e., bottom-up mass spectrometry [MS]). For top-down MS, proteome fractionation acts as a stand-alone separation platform, since intact proteins are directly analyzed by the mass spectrometer. Regardless of the MS identification strategy, separation of intact proteins has clear benefits as a result of decreasing sample complexity. However, this stage of the workflow also creates considerable challenges, which are generally absent from the counterpart peptide separation experiment. For example, maintaining protein solubility is a key concern before, during and after separation. To this end, surfactants such as sodium dodecyl sulfate may be employed during fractionation, so long as they are eliminated prior to MS. In this article, current strategies for proteome fractionation in a MS-compatible format are reviewed, illustrating the challenges and outlooks on this important aspect of proteomics. PMID- 22087663 TI - Post-genomics of Neisseria meningitidis: an update. AB - Neisseria meningitidis infection still remains a major life-threatening bacterial disease worldwide. The availability of bacterial genomic sequences generated a paradigm shift in microbiological and vaccines sciences, and post-genomics (comparative genomics, functional genomics, proteomics and a combination/evolution of these techniques) played important roles in elucidating bacterial biological complexity and pathogenic traits, at the same time accelerating the development of therapeutic drugs and vaccines. This article summarizes the most recent technological and scientific advances in meningococcal biology and pathogenesis aimed at the development and characterization of vaccines against the pathogenic meningococci. PMID- 22087667 TI - Twentieth-century cohort marriage and divorce in England and Wales. AB - Summary Marital status life tables, which follow a real or synthetic birth cohort through life and the marital statuses of 'never married', 'presently married', 'widowed', and 'divorced', reflect observed marriage, divorce and mortality behaviour and provide a detailed record of a cohort's experience. The present paper analyses such tables for cohorts of men and women born in England and Wales between 1900 and 1945. The results show that the later cohorts deviate substantially from the 'European pattern' of late marriage and high proportions never marrying, and that a dramatic rise in divorce has taken place, so that among the later cohorts one marriage out of four ends in divorce. PMID- 22087669 TI - Analysing open birth interval distributions. AB - Summary This paper began with the recognition that open birth interval distributions are analogous to age distributions. It then became clear that closed birth interval distributions are, somewhat more loosely, analogous to mortality schedules, and that the relationship between open and closed birth interval distributions could be explored by imitating the formal demography of mortality and age distribution. Pursuing this programme, we develop the formal demography of open and closed birth interval distributions and show that under certain assumptions open interval distributions may be used to estimate closed interval distributions, just as age distributions may be used to estimate mortality. An illustrative application to Indonesian data is given. PMID- 22087670 TI - Estimation of adult mortality using forward and backward projections. AB - Summary In this paper it is shown that, contrary to our intuitive understanding of the nature of population projection, the estimation of adult intercensal mortality leads to different results depending on whether forward or backward projection of the population is used. From this result a simple procedure is developed that yields estimates of the completeness of adult mortality registration. Finally, the nature and performance of a variety of methods that have recently been developed to estimate adult mortality in the absence of accurate data are compared. PMID- 22087666 TI - Social class and socio-economic differentials in divorce in England and Wales. AB - Summary The characteristics of a national sample of over 2,000 couples who divorced in 1979 are analysed according to the social class and socio-economic position of the husband. The demographic variables investigated for social class and socio-economic differentials include ages at marriage and divorce, duration of marriage, previous marital status, family size and the presence of a pre maritally conceived child. In addition, an age-standardized measure, the 'standardized divorce ratio' is used to summarise the relative rates of divorce for the different social classes and socio-economic groups. Using this measure, the rate of divorce for couples in Social Class I is only half that for the average couple, whereas for couples in Social Class V and couples in which the husband is unemployed it is more than double. PMID- 22087664 TI - Bluestockings, spinsters and pedagogues: Women college graduates, 1865-1910. AB - Summary This article is a study of the demographic behaviour of women college graduates in late nineteenth and early twentieth-century America. The nuptiality and fertility patterns of this group of highly educated women are described, and several explanations of their 'unusual' behaviour are evaluated. Marriage rates of women college graduates declined during the second half of the nineteenth century, even as more women attended college. Only about half the women graduating during the 1890s ever married. Still, the number of children ever born per alumna only varied between 1.0 and 1.5 for the graduation classes of 1865 to 1910. An explanation based on changing labour market opportunities for educated men and women best explains this population's demographic patterns over time as well as their deviations from those of other women in their birth cohort. PMID- 22087668 TI - The effects of children on divorce and re-marriage: a multivariate analysis of life table probabilities. AB - Summary Using proportional hazards models and multiple decrement life tables to analyse data from the 1973 National Survey of Family Growth, this study tests the hypotheses that, net of the effects of such factors as age at separation or divorce, the probabilities of divorce after separation and of re-marriage after divorce would be lower for women with larger numbers of children or younger children, and that these transitions would take longer than for women with fewer or older children or women who were childless; and that there would be an interaction between number of children and age of youngest child. Results included: (1) the probability that mothers of two or more children would divorce after separation was significantly lower than for childless women, or those with only one child; (2) among whites, mothers of three or more children were at a significant disadvantage regarding their chances of re-marriage, whereas the probability that a black mother of three or more children would re-marry was no smaller than that of a woman with fewer or no children; (3) among whites, the presence of a youngest child aged between two and five years at separation decreased the probability of divorce after separation; (4) there was no interaction effect between number and age of children; and (5) in each category of family size and age of youngest child, the probability that a black woman would divorce after separation or re-marry after divorce was lower than for white women. The results have important implications for the study of divorce and re marriage, and for understanding of problems of single-parent families. PMID- 22087673 TI - A rejoinder to S. K. Datta and J. B. Nugent. AB - Abstract Extract The question of old-age security as a motivation for fertility in less-developed rural areas can be put in clearer perspective by pausing to consider the changing roles of land and offspring under the influence of fundamental demographic upheaval. Under the pre-transition regime, one generation approximately replaced the preceding one, particularly once unused but usable land became scarce and the possibility of expanding farm operations became remote. Judging from the settlement patterns and the history of the Maharashtrian study area, such a circumstance probably obtained long before the secular drop in mortality began. During this period, a single son, typically, would survive to adulthood, gradually assuming control of the father's land (or the father's trade, among non-agriculturalists) and, if the father lived long enough, would eventually be a source of security in the father's old age. It is not inappropriate to mention that this generational cycle no doubt fostered a strong urge to leave the family land to a son, so that a sonless farmer would keenly feel a lack of fulfilment. In fact, responses to certain survey questions suggest that ancestral land and male progeny are still somehow connected, according to the way village men think, to their sense of immortality. It would be hard, consequently, to separate old-age security, the idea of 'continuing a lineage', and the sense of immortality conferred by owning land into distinct motives for conceiving children. PMID- 22087677 TI - The public, political parties, and stem-cell research. PMID- 22087671 TI - Transforming gompertz's function for fertility analysis: The development of a standard for the relational gompertz function. AB - Summary The relational Gompertz function improves upon the Gompertz for fertility analysis by achieving a better fit in the tails of the distribution. This is obtained by a transformation of the age scale corresponding to an empirical standard. This standard is developed from Coale and Trussell's model and is appropriate for use with populations of high fertility. The model is tested on two sets of data and is shown to produce good estimates of completed fertility even for data truncated at quite early ages. Good results are also obtained for declining fertility. PMID- 22087672 TI - Are old-age security and the utility of children in rural India really unimportant? AB - Abstract Extract In their recent paper in this journal M. and Carol Vlassoff are to be commended for helping to remedy the dearth of empirical studies on the old-age security motive for children (and particularly sons) in rural areas of developing countries.(1) However, while the questionnaire which they applied to 357 ever-married men in a rural village in Maharashtra state in India is potentially useful, several of the conclusions they derive from it are unwarranted and, if left unquestioned, would undoubtedly have the effect of setting back the serious investigation of the effects of this motive rather than furthering it. The invalid or at least questionable inferences are taken up one at a time in the order of their appearance: PMID- 22087678 TI - War, drought, malnutrition, measles--a report from Somalia. PMID- 22087683 TI - Case records of the Massachusetts General Hospital. Case 35-2011: A 33-year-old woman with postpartum leukocytosis and Gram-positive bacteremia. PMID- 22087682 TI - Images in clinical medicine: A tension bulla mimicking tension pneumothorax. PMID- 22087681 TI - Extracorporeal membrane oxygenation for ARDS in adults. AB - A 41-year-old woman presents with severe community-acquired pneumococcal pneumonia. Chest radiography reveals diffuse bilateral infiltrates, and hypoxemic respiratory failure develops despite appropriate antibiotic therapy. She is intubated and mechanical ventilation is initiated with a volume- and pressure limited approach for the acute respiratory distress syndrome (ARDS). Over the ensuing 24 hours, her partial pressure of arterial oxygen (Pao2) decreases to 40 mm Hg, despite ventilatory support with a fraction of inspired oxygen (Fio2) of 1.0 and a positive end-expiratory pressure (PEEP) of 20 cm of water. She is placed in the prone position and a neuromuscular blocking agent is administered, without improvement in her Pao2. An intensive care specialist recommends the initiation of extracorporeal membrane oxygenation (ECMO). PMID- 22087684 TI - Childhood obesity and coronary heart disease. PMID- 22087685 TI - Toward better treatment for lupus nephritis. PMID- 22087691 TI - Tissue plasminogen activator and DNase in empyema. PMID- 22087689 TI - Prevention of HIV-1 infection with antiretroviral therapy. PMID- 22087695 TI - Chimeric antigen receptor-modified T cells in CLL. PMID- 22087698 TI - Malpractice risk according to physician specialty. PMID- 22087688 TI - Prevention of HIV-1 infection with antiretroviral therapy. PMID- 22087694 TI - Chimeric antigen receptor-modified T cells in CLL. PMID- 22087679 TI - Childhood adiposity, adult adiposity, and cardiovascular risk factors. AB - BACKGROUND: Obesity in childhood is associated with increased cardiovascular risk. It is uncertain whether this risk is attenuated in persons who are overweight or obese as children but not obese as adults. METHODS: We analyzed data from four prospective cohort studies that measured childhood and adult body mass index (BMI, the weight in kilograms divided by the square of the height in meters). The mean length of follow-up was 23 years. To define high adiposity status, international age-specific and sex-specific BMI cutoff points for overweight and obesity were used for children, and a BMI cutoff point of 30 was used for adults. RESULTS: Data were available for 6328 subjects. Subjects with consistently high adiposity status from childhood to adulthood, as compared with persons who had a normal BMI as children and were nonobese as adults, had an increased risk of type 2 diabetes (relative risk, 5.4; 95% confidence interval [CI], 3.4 to 8.5), hypertension (relative risk, 2.7; 95% CI, 2.2 to 3.3), elevated low-density lipoprotein cholesterol levels (relative risk, 1.8; 95% CI, 1.4 to 2.3), reduced high-density lipoprotein cholesterol levels (relative risk, 2.1; 95% CI, 1.8 to 2.5), elevated triglyceride levels (relative risk, 3.0; 95% CI, 2.4 to 3.8), and carotid-artery atherosclerosis (increased intima-media thickness of the carotid artery) (relative risk, 1.7; 95% CI, 1.4 to 2.2) (P <= 0.002 for all comparisons). Persons who were overweight or obese during childhood but were nonobese as adults had risks of the outcomes that were similar to those of persons who had a normal BMI consistently from childhood to adulthood (P>0.20 for all comparisons). CONCLUSIONS: Overweight or obese children who were obese as adults had increased risks of type 2 diabetes, hypertension, dyslipidemia, and carotid-artery atherosclerosis. The risks of these outcomes among overweight or obese children who became nonobese by adulthood were similar to those among persons who were never obese. (Funded by the Academy of Finland and others.). PMID- 22087697 TI - Malpractice risk according to physician specialty. PMID- 22087692 TI - Tissue plasminogen activator and DNase in empyema. PMID- 22087665 TI - The Effect of birth spacing on childhood mortality in Pakistan. AB - Summary In this study retrospective data from the 1975 Pakistan Fertility Survey are used to examine the effects of birth spacing on infant and child mortality. The length of the preceding interval between live births emerges as a major determinant of mortality. The effect persists for rural and urban families, for children of uneducated and educated mothers, for both boys and girls, and for large and small families. The possibility that this relationship is the spurious consequence of data defects or of a common cause, such as early weaning, is examined but rejected. Once the length of the preceding interval is controlled, the average spacing of earlier births is found to be unrelated to survivorship. However, the length of the succeeding interval is significantly related to survivorship during the second year of life. PMID- 22087699 TI - HRAS mutation mosaicism causing urothelial cancer and epidermal nevus. PMID- 22087686 TI - Beta-cell failure, stress, and type 2 diabetes. PMID- 22087704 TI - Images in clinical medicine: Zoster of the tympanic membrane. PMID- 22087707 TI - Local structure and charge distribution in mixed uranium-americium oxides: effects of oxygen potential and Am content. AB - Partitioning and transmutation (P&T) of minor actinides (MA) is currently studied to reduce the nuclear waste inventory. In this context, the fabrication of MA bearing materials is of great interest to achieve an effective recycling of these highly radioactive elements. To ensure the in-pile behavior, nuclear oxide fuels have to respect several criteria including preservation of the fluorite structure and defined oxygen to metal ratio (O/M). In the case of Am bearing materials, such as U(1-y)Am(y)O(2+/-x) (y = 0.10, 0.15, 0.20), the O/M determination is quite challenging using conventional methods (TGA, XRD) because of the particular thermodynamic properties of Am. Despite the lack of experimental data in the U-Am O system, thermodynamical models are currently developed to effectively assess the O/M ratio. In this work, the O/M ratios were calculated for various oxygen potentials using the cation molar fraction determined by XAS measurements. These results are an important addition to the experimental data available for the U-Am O system. Moreover, XRD and XAS indicated that the fabrication of fluorite U(1 y)Am(y)O(2+/-x) solid solution was achieved for all Am content and oxygen potentials investigated. On the basis of the molar fraction, a description of the solid solution was proposed depending on the considered sintering conditions. Finally, the occurrence of an unexpected charge compensation mechanism was pointed out. PMID- 22087705 TI - Work ability: concept and assessment from a physiotherapeutic perspective. An interview study. AB - The aim of this study was to ascertain experiences and perceptions among physiotherapists (PTs) in Sweden regarding the concept of work ability as well as their perspectives of their professional role in work ability assessments. We conducted an in-depth interview study with four male and twelve female physiotherapists working in the field of occupational health care, orthopaedics, primary health care or rehabilitation. Qualitative content analysis was applied to the data. Work ability was perceived as the ability to perform work tasks as requested. Having the potential to adjust at work and to allocate resources, having an attachment to the workplace and time factors were vital. The physiotherapists were striving for a well-defined role within a multiprofessional team, where work ability assessments were performed in a real work environment. The PTs experienced contradictory roles in relation to the patient but believed they could contribute with valuable material for assessments; this professional help was not always requested. It was noted that there was a need for experience and further education to enable PTs to further engage in work ability assessments. It is important to improve collaboration and to further discuss the work ability concept from the viewpoints of different professionals. PMID- 22087708 TI - Influence of electric field on SERS: frequency effects, intensity changes, and susceptible bonds. AB - The fundamental mechanism proposed to explain surface-enhanced Raman scattering (SERS) relies on electromagnetic field enhancement at optical frequencies. In this work, we demonstrate the use of microfabricated, silver nanotextured electrode pairs to study, in situ, the influence of low frequency (5 mHz to 1 kHz) oscillating electric fields on the SERS spectra of thiophenol. This applied electric field is shown to affect SERS peak intensities and influence specific vibrational modes of the analyte. The applied electric field perturbs the polar analyte, thereby altering the scattering cross section. Peaks related to the sulfurous bond which binds the molecule to the silver nanotexture exhibit strong and distinguishable responses to the applied field, due to varying bending and stretching mechanics. Density functional theory simulations are used to qualitatively verify the experimental observations. Our experimental and simulation results demonstrate that the SERS spectral changes relate to electric field induced molecular reorientation, with dependence on applied field strength and frequency. This demonstration creates new opportunities for external dynamic tuning and multivariate control of SERS measurements. PMID- 22087710 TI - Changing the world with an embryo. PMID- 22087680 TI - Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. AB - BACKGROUND: Maintenance therapy, often with azathioprine or mycophenolate mofetil, is required to consolidate remission and prevent relapse after the initial control of lupus nephritis. METHODS: We carried out a 36-month, randomized, double-blind, double-dummy, phase 3 study comparing oral mycophenolate mofetil (2 g per day) and oral azathioprine (2 mg per kilogram of body weight per day), plus placebo in each group, in patients who met response criteria during a 6-month induction trial. The study group underwent repeat randomization in a 1:1 ratio. Up to 10 mg of prednisone per day or its equivalent was permitted. The primary efficacy end point was the time to treatment failure, which was defined as death, end-stage renal disease, doubling of the serum creatinine level, renal flare, or rescue therapy for lupus nephritis. Secondary assessments included the time to the individual components of treatment failure and adverse events. RESULTS: A total of 227 patients were randomly assigned to maintenance treatment (116 to mycophenolate mofetil and 111 to azathioprine). Mycophenolate mofetil was superior to azathioprine with respect to the primary end point, time to treatment failure (hazard ratio, 0.44; 95% confidence interval, 0.25 to 0.77; P = 0.003), and with respect to time to renal flare and time to rescue therapy (hazard ratio, <1.00; P < 0.05). Observed rates of treatment failure were 16.4% (19 of 116 patients) in the mycophenolate mofetil group and 32.4% (36 of 111) in the azathioprine group. Adverse events, most commonly minor infections and gastrointestinal disorders, occurred in more than 95% of the patients in both groups (P = 0.68). Serious adverse events occurred in 33.3% of patients in the azathioprine group and in 23.5% of those in the mycophenolate mofetil group (P = 0.11), and the rate of withdrawal due to adverse events was higher with azathioprine than with mycophenolate mofetil (39.6% vs. 25.2%, P = 0.02). CONCLUSIONS: Mycophenolate mofetil was superior to azathioprine in maintaining a renal response to treatment and in preventing relapse in patients with lupus nephritis who had a response to induction therapy. (Funded by Vifor Pharma [formerly Aspreva]; ALMS ClinicalTrials.gov number, NCT00377637.). PMID- 22087700 TI - Nitric oxide during altitude acclimatization. PMID- 22087706 TI - A qualitative exploration of smokers' views regarding aspects of a community based mobile stop smoking service in the United Kingdom. AB - BACKGROUND: Developing more accessible stop smoking services (SSS) is important, particularly for reaching smokers from socio-economically deprived groups who are more likely to smoke and less likely to quit in comparison to their more affluent counterparts. A drop-in mobile SSS (MSSS) was piloted across 13 locations in socio-economically deprived areas of Nottingham. METHODS: Semi-structured telephone interviews were conducted to explore the views of 40 smokers who registered with the MSSS. RESULTS: The MSSS appeared to trigger quit attempts. For some of the participants the attempt was totally unplanned; for others, it built on pre-existing thoughts about quitting which had not yet been acted upon. Smokers interested in quitting were comfortable about approaching the MSSS, whilst acknowledging that they did not feel pressured to register with the service. The drop-in format of the MSSS was found to be more appealing than making an appointment. In addition, several participants articulated that they may not have utilised other SSS had they not come across the MSSS. CONCLUSIONS: A MSSS may be an effective way to prompt quit attempts for smokers not planning to quit and also reach smokers who would not engage with SSS. PMID- 22087711 TI - More on change and veterinary medical education. PMID- 22087712 TI - Ovariohysterectomy versus ovariectomy for elective sterilization of female dogs and cats: is removal of the uterus necessary? PMID- 22087713 TI - Supravalvular PA stenosis (PAS) of probable congenital origin. PMID- 22087719 TI - Pathology in practice. Mannheimia haemolytica. PMID- 22087720 TI - Therapeutic use of fish oils in companion animals. PMID- 22087716 TI - Anesthesia case of the month. Administration of aged packed RBCs. PMID- 22087722 TI - Phenylpropanolamine toxicosis in dogs: 170 cases (2004?2009). AB - OBJECTIVE: To evaluate signalment, clinical signs, dose ingested, treatment requirements, duration of hospitalization, and outcome of dogs exposed to phenylpropanolamine. DESIGN: Retrospective case series. ANIMALS: 170 dogs with potential PPA toxicosis evaluated between 2004 and 2009. PROCEDURES: Dogs with potential PPA toxicosis were identified by reviewing the electronic database of an animal poison control center. RESULTS: 66 of the 170 (39%) dogs reportedly did not develop any clinical signs. Clinical signs reported in the remaining 104 (61%) dogs included agitation (n = 40), vomiting (27), mydriasis (19), lethargy (17), tremor or twitching (16), panting (15), bradycardia (13), tachycardia (12), hypertension (11), and erythema (8). Median dose ingested for all dogs was 29 mg/kg (13.2 mg/lb). Dogs developing clinical signs had a significantly higher median dose ingested (373 mg/kg [170 mg/lb]) than did dogs that did not develop clinical signs (18 mg/kg [8.2 mg/lb]). Likewise, median dose ingested for the 123 dogs treated as inpatients (36.9 mg/kg [16.8 mg/lb]) was significantly higher than the median dose for the 14 dogs treated as outpatients (20.5 mg/kg [9.3 mg/lb]). Median duration of hospitalization was 18 hours (range, 4 to 72 hours), and hospitalization time increased as the dose ingested increased. Survival rate was 99.4% (169/170); the dog that died had ingested a dose of 145 mg/kg (65.9 mg/lb). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that with supportive care, the prognosis for dogs that had ingested an overdose of phenylpropanolamine was excellent. PMID- 22087718 TI - Animal behavior case of the month. Feline urine marking. PMID- 22087723 TI - Clinical signs and histologic findings in dogs with odontogenic cysts: 41 cases (1995-2010). AB - OBJECTIVE: To characterize clinical signs and histologic findings in dogs with odontogenic cysts and determine whether histologic findings were associated with clinical features. DESIGN: Retrospective case series. ANIMALS: 41 dogs. PROCEDURES: Medical records were reviewed to obtain clinical data, including breed, age, sex, and lesion location. Microscopic sections and results of diagnostic imaging were reviewed. RESULTS: Odontogenic cysts were identified in 41 dogs between 1995 and 2010. There were 29 dogs with dentigerous cysts, 1 with a radicular cyst, 1 with a lateral periodontal cyst, and 1 with a gingival inclusion cyst. In addition, 9 dogs with odontogenic cysts that had clinical and histologic features suggestive of, but not diagnostic for, odontogenic keratocysts seen in people were identified. In all 9 dogs, these cysts were located in the maxilla and surrounded the roots of normally erupted teeth. Of the 29 dogs with dentigerous cysts, 23 had a single cyst, 5 had 2 cysts, and 1 had 3 cysts. Six cysts were associated with an unerupted canine tooth, and 30 were associated with an unerupted first premolar tooth (1 cyst was associated both with an unerupted canine tooth and with an unerupted first premolar tooth). Dentigerous cysts were identified in a variety of breeds, but several brachycephalic breeds were overrepresented, compared with the hospital population during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a variety of odontogenic cysts can occur in dogs. In addition, cysts that resembled odontogenic keratocysts reported in people were identified. We propose the term canine odontogenic parakeratinized cyst for this condition. PMID- 22087725 TI - Abdominal computed radiography for the diagnosis of enterolithiasis in horses: 142 cases (2003?2007). AB - OBJECTIVE: To evaluate the sensitivity and specificity of abdominal computed radiography (CR) for the diagnosis of enterolithiasis in horses and to examine how these parameters are affected by the number and anatomic location of enteroliths and by gas distension of the gastrointestinal tract. DESIGN: Retrospective case series. ANIMALS: Horses ? 1 year old that underwent abdominal CR and subsequent exploratory laparotomy or postmortem examination. PROCEDURES: 3 reviewers blinded to signalment, history, clinical signs, and diagnoses separately evaluated abdominal computed radiographs of horses included in the study. Each set of radiographs was evaluated for the presence or absence of enteroliths, the amount of gas distention, and the image quality. Signalment, definitive diagnosis on the basis of findings on exploratory laparotomy or postmortem examination, and the number and location of enteroliths were obtained from medical records. RESULTS: Of the 142 cases reviewed, 58.4% (83/142) had confirmed enterolithiasis. For the 3 reviewers, overall sensitivity was 85% and specificity was 93%. Sensitivity was lower for small colon enteroliths than for large colon enteroliths (50% and 94.5%, respectively) and was significantly affected by gas distention. Sensitivity was not significantly affected by the number of enteroliths. CONCLUSIONS AND CLINICAL RELEVANCE: Computed radiography provided high sensitivity and high specificity for the diagnosis of enterolithiasis in horses. Caution should be exercised when the radiographic results are negative, as the sensitivity for small colon enterolithiasis was relatively low and gas distension negatively affected detection of enteroliths. Abdominal CR is indicated as a diagnostic test in horses examined for colic in geographic regions in which enterolithiasis is endemic. PMID- 22087724 TI - Monoclonal immunoglobulin protein production in two dogs with secretory B-cell lymphoma with mott cell differentiation. AB - CASE DESCRIPTION: A 9-year-old castrated male mixed-breed dog and a 7-year-old spayed female Boston Terrier, with clinical histories of a liver mass (dog 1) and bloody vomitus, diarrhea, and weight loss (dog 2), respectively, were referred for further evaluation. CLINICAL FINDINGS: At the time of referral, each dog had differing laboratory abnormalities; however, the serum total protein and globulin concentrations were within reference range in both dogs. Cytologic examination of fine-needle aspirates obtained from affected organs (a liver mass [dog 1] and enlarged submandibular lymph node [dog 2]) revealed 2 main nucleated cell types: atypical lymphoid cells and lesser numbers of Mott cells. With the use of serum immunofixation electrophoresis and serum immunoglobulin quantification, a monoclonal immunoglobulin protein was identified in both dogs and a final diagnosis of secretory B-cell lymphoma with Mott cell differentiation (MCL) was made. TREATMENT AND OUTCOME: Both dogs received chemotherapy for their disease. The first dog was euthanized 8.5 months after diagnosis because of acute respiratory distress of unknown etiology, and the second was euthanized 7 days after diagnosis for worsening clinical disease and quality of life. CLINICAL RELEVANCE: To our knowledge, this report is the first of a secretory form of MCL in dogs. Findings indicate that in dogs with suspect MCL, even in patients that lack characteristic hyperproteinemia or hyperglobulinemia, serum protein content should be fully evaluated for the presence of a monoclonal immunoglobulin protein. Such an evaluation that uses immunofixation electrophoresis and immunoglobulin quantification will aid in the diagnosis of MCL in dogs. PMID- 22087729 TI - Palladium-catalyzed benzylation of unprotected anthranilic acids with benzyl alcohols in water. AB - Palladium-catalyzed benzylation of unprotected anthranilic acids with benzyl alcohols in the presence of Pd(OAc)(2) (5 mol %) and sodium diphenylphosphinobenzene-3-sulfonate (TPPMS, 10 mol %) in water at 120 degrees C for 16 h gave only dibenzylated anthranilic acids in good yields. Water may play important roles for the smooth generation of the (eta(3)-benzyl)palladium species by activation of the hydroxyl group of the benzyl alcohol. PMID- 22087727 TI - The headache of high altitude and microgravity--similarities with clinical syndromes of cerebral venous hypertension. AB - Syndromes thought to have cerebral venous hypertension as their core, such as idiopathic intracranial hypertension and jugular foramen outlet obstruction, classically result in headaches. Do they provide an insight into the cause of the headache that commonly occurs at altitude? The classic theory of the pathogenesis of high altitude headache has been that it results from increased intracranial pressure (ICP) secondary to hypoxemia in people who have less compliant intracranial volumes (Roach and Hackett, 2001). However, there does not appear to be a correlation between the headache of acute mountain sickness (AMS) and the presence of cerebral edema (Bailey et al, 2006; Wilson et al, 2009). Research has concentrated on arterial perfusion to the brain in hypoxia, but there has been little study of venous drainage. Hypoxia results in markedly increased cerebral blood flow; however, if it has been considered at all, venous outflow has to date been assumed to be of little consequence. Retinal venous distension and the increased venous blood demonstrated by near infra-red spectroscopy and more recently by MRI imply that, in hypoxia, a relative venous insufficiency may exist. Similarly, there is increasing evidence that manifestations of the fluid shift during microgravity is of similar nature to idiopathic intracranial hypertension, which is thought to be primarily a venous insufficiency condition. The unique anthropomorphic adaptations of large brained biped humans with cerebral venous systems that have to cope with large changes in hydrostatic pressure may predispose us to conditions of inflow/outflow mismatch. In addition, slight increases in central venous pressures (e.g., from hypoxia-induced pulmonary vasoconstriction) may further compromise venous outflow at altitude. A better understanding of cerebral venous physiology may enlighten us with regards the pathogenesis of headaches currently considered idiopathic. It may also enable us to trigger headaches for study and hence enable us to develop new treatment strategies. PMID- 22087728 TI - Structures and IR spectra of the Gramicidin S peptide: pushing the quest for low energy conformations. AB - An extensive molecular modeling study was carried out on the doubly protonated cyclic decapeptide Gramicidin S following several recent gas-phase experiments. Our computational strategy includes replica-exchange molecular dynamics simulations with the new generation force field AMOEBA for exploration and density functional calculations using several functionals for refinement of structures and computation of IR spectra. This procedure yields low-energy structures of which three are proposed to correspond to the three conformers detected in low-temperature IR experiments. The most stable structure has C(2) symmetry and four strong beta-sheet interactions between Orn and Val residues. Furthermore, all the other peptidic N-H bonds are involved in seven-membered C(7) motifs. The computed IR spectra of the three conformers are in good agreement with the experimental ones in the 1400-2000 cm(-1) range. In the 3000-3600 cm(-1) region, the computed spectrum is also in good agreement with experiment for the main conformer, and predictions are made of structure-specific signatures for the other two conformers. The accuracy of several density functionals is discussed in detail. These results point out that efficient potential energy surface explorations coupled to appropriate density functional theory (DFT) calculations are able to reveal the structures of molecules as large and flexible as decapeptides. PMID- 22087721 TI - Evaluation of dexmedetomidine and ketamine in combination with various opioids as injectable anesthetic combinations for castration in cats. AB - OBJECTIVE: To compare the efficacy and cardiorespiratory effects of dexmedetomidine-ketamine in combination with butorphanol, hydromorphone, or buprenorphine with or without reversal by atipamezole in cats undergoing castration. DESIGN: Prospective, randomized, split-plot, blinded study. ANIMALS: 30 healthy male cats. PROCEDURES: Cats were assigned to receive dexmedetomidine (25 ?g/kg [11.4 ?g/lb]) and ketamine (3 mg/kg [1.4 mg/lb]) with butorphanol (0.2 mg/kg [0.09 mg/lb]; DKBut; n = 10), hydromorphone (0.05 mg/kg [0.023 mg/lb]; DKH; 10), or buprenorphine (30 ?g/kg [13.6 ?g/lb]; DKBup; 10). Drugs were administered as a single IM injection. Supplemental isoflurane was administered to cats if the level of anesthesia was inadequate for surgery. At the conclusion of surgery, half the cats (5 cats in each treatment group) received atipamezole (250 ?g/kg [113.6 ?g/lb], IM) and the remainder received saline (0.9% NaCl) solution IM. All cats received meloxicam (0.2 mg/kg, SC) immediately prior to the conclusion of surgery. RESULTS: All drug combinations induced lateral recumbency, and intubation was achievable in 13 of 30 (43%) cats at 10 minutes after injection. Supplemental isoflurane was needed for the surgery in 1 of 10 of the DKBut-, 2 of 10 of the DKH-, and 7 of 10 of the DKBup-treated cats. Cats that received atipamezole had a significantly shorter recovery time. CONCLUSIONS AND CLINICAL RELEVANCE: DKBut and DKH combinations were suitable injectable anesthetic protocols for castration in cats commencing at 10 minutes after injection, but cats receiving DKBup may require additional time or anesthetics for adequate anesthesia. PMID- 22087715 TI - ECG of the Month. ECG Interpretation. PMID- 22087714 TI - Diagnostic imaging in veterinary dental practice. Chronic endodontic disease of the right mandibular first molar tooth. PMID- 22087731 TI - The utility of a bladder scan protocol using a portable ultrasonographic device in subacute stroke patients. AB - PURPOSE: To evaluate the clinical usefulness of a bladder scan protocol for measuring urinary retention with a Portable Ultrasonographic Device (PUD) in stroke patients. METHOD: This is case-control study. The study enrolled a total of 52 stroke patients with post-void residual urine (PVR) volume > 100 mL. The case group (n = 26) was managed using our bladder scan protocol until the PVR volume fell below 100 mL. A PVR volume > 400 mL resulted in intermittent urinary catheterization (IC). The control group (n = 26) was not managed using the bladder scan protocol. We compared outcomes for the two groups. RESULTS: The case and control groups were similar in terms of the total scanning period (days). The number of scanning days after the PVR volume fell below < 100 mL was less for the case than the control group (2.3 versus 8.5 days; p < 0.001). Scanning was discontinued before the PVR volume fell below 100 mL in one case group and seven control group patients (p < 0.05). The mean IC volume was nearly 400 mL in the case group, without any bladder overdistensions and without any urinary tract infections. CONCLUSIONS: Our bladder scan protocol for urinary retention after stroke may be useful as this allows catheterization of an adequate urine volume and reduces unnecessary bladder scanning. PMID- 22087730 TI - Role of hexaminolevulinate-guided fluorescence cystoscopy in bladder cancer: critical analysis of the latest data and European guidance. AB - OBJECTIVE: Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL-FC has a role in improving detection of NMIBC and provide recommendations on situations for its use. Since the publication of the EAU guidelines and the European consensus statement, new evidence on the efficacy of HAL-FC in reducing recurrence of NMIBC, compared with white light cystoscopy (WLC), have been published. MATERIAL AND METHODS: To consider whether these new trials have an impact on the expert guidelines and on clinical practice (e.g. supporting existing recommendations or providing evidence for a change or expansion of practice), a group of bladder cancer experts from Denmark, Finland, Norway and Sweden met to address the following questions: What is the relevance of the new data on HAL-FC for clinical practice in managing NMIBC? What impact do the new data have on European guidelines? How could HAL-FC be used in clinical practice? and What further information on HAL-FC is required to optimize the management of NMIBC? RESULTS AND CONCLUSIONS: This article reports the outcomes of the discussion at the Nordic expert panel meeting, concluding that, in line with European guidance, HAL-FC has an important role in the initial detection of NMIBC and for follow-up of patients to assess tumour recurrence after WLC. It provides practical advice, with an algorithm on the use of this diagnostic procedure for urologists managing NMIBC. PMID- 22087726 TI - Fish polar lipids retard atherosclerosis in rabbits by down-regulating PAF biosynthesis and up-regulating PAF catabolism. AB - BACKGROUND: Platelet activating factor (PAF) has been proposed as a key factor and initial trigger in atherosclerosis. Recently, a modulation of PAF metabolism by bioactive food constituents has been suggested. In this study we investigated the effect of fish polar lipid consumption on PAF metabolism. RESULTS: The specific activities of four PAF metabolic enzymes; in leukocytes, platelets and plasma, and PAF concentration; either in blood cells or plasma were determined. Samples were acquired at the beginning and at the end of a previously conducted study in male New Zealand white rabbits that were fed for 45 days with atherogenic diet supplemented (group-B, n = 6) or not (group-A, n = 6) with gilthead sea bream (Sparus aurata) polar lipids.The specific activity of PAF Acetylhydrolase (PAF-AH); a catabolic enzyme of PAF, was decreased in rabbits' platelets of both A and B groups and in rabbits' leukocytes of group A (p < 0.05). On the other hand the specific activity of Lipoprotein-associated Phospholipase A2 (Lp-PLA2); the catabolic enzyme of PAF in plasma was increased in both A and B groups in both leukocytes and platelets (p < 0.05). PAF cholinephosphotransferase (PAF-CPT); a biosynthetic enzyme of PAF showed increased specific activity only in rabbits' leukocytes of group A (p < 0.05). Neither of the two groups showed any change in Lyso-PAF-acetyltransferase (Lyso PAF-AT) specific activity (p > 0.05). Free and bound PAF levels increased in group A while decreased in group B (p < 0.05). CONCLUSIONS: Gilthead sea bream (Sparus aurata) polar lipids modulate PAF metabolism upon atherosclerotic conditions in rabbits leading to lower PAF levels and activity in blood of rabbits with reduced early atherosclerotic lesions compared to control group. PMID- 22087732 TI - Vibrational spectroscopic determination of local solvent electric field, solute solvent electrostatic interaction energy, and their fluctuation amplitudes. AB - IR probes have been extensively used to monitor local electrostatic and solvation dynamics. Particularly, their vibrational frequencies are highly sensitive to local solvent electric field around an IR probe. Here, we show that the experimentally measured vibrational frequency shifts can be inversely used to determine local electric potential distribution and solute-solvent electrostatic interaction energy. In addition, the upper limits of their fluctuation amplitudes are estimated by using the vibrational bandwidths. Applying this method to fully deuterated N-methylacetamide (NMA) in D(2)O and examining the solvatochromic effects on the amide I' and II' mode frequencies, we found that the solvent electric potential difference between O(?C) and D(-N) atoms of the peptide bond is about 5.4 V, and thus, the approximate solvent electric field produced by surrounding water molecules on the NMA is 172 MV/cm on average if the molecular geometry is taken into account. The solute-solvent electrostatic interaction energy is estimated to be -137 kJ/mol, by considering electric dipole-electric field interaction. Furthermore, their root-mean-square fluctuation amplitudes are as large as 1.6 V, 52 MV/cm, and 41 kJ/mol, respectively. We found that the water electric potential on a peptide bond is spatially nonhomogeneous and that the fluctuation in the electrostatic peptide-water interaction energy is about 10 times larger than the thermal energy at room temperature. This indicates that the peptide-solvent interactions are indeed important for the activation of chemical reactions in aqueous solution. PMID- 22087733 TI - Exposure to a dog elicits different cardiovascular and behavioral effects in pregnant and lactating goats. AB - BACKGROUND: Heart rate and plasma cortisol concentration are often used in evaluation of physiological reactions to stress and fear, but arterial blood pressure is rarely measured in farm animals. Goats are prey animals and can be expected to react strongly to a predator, especially when they have kids. We hypothesized that exposure to a dog elicits a flight response during pregnancy and a fight response when goats have kids to defend. Arterial blood pressure and heart rate should increase in both these cases, due to a synchronized discharge of the sympathetic nervous system. METHODS: Seven goats were exposed to a dog for 15 minutes at 12 +/- 3 days before, and again at 10 +/- 1 days after, parturition. Arterial blood pressure, heart rate, and activity were registered by telemetry. Behavioral data were collected during 5 minute sessions, followed by blood samples obtained via intrajugular catheters. Plasma cortisol concentration was analyzed by radioimmunoassay. RESULTS: At the appearance of the dog, the mean arterial blood pressure of the goats increased from 90 +/- 8 to 111 +/- 8 mmHg (p < 0.001) during pregnancy and from 96 +/- 8 to 108 +/- 8 mmHg during lactation (p < 0.001). Heart rate did not change at dog exposure during lactation, but increased from 117 +/- 6 to 126 +/- 10 beats/min (p < 0.01) during pregnancy. Dog exposure resulted in plasma cortisol concentration increasing from 17 +/- 1 to 43 +/- 7 nmol/l (p < 0.01) during pregnancy and from 21 +/- 1 to 49 +/- 6 nmol/l (p < 0.01) during lactation. In response to the dog, goats vocalized at a higher frequency and started to ruminate later during lactation compared to pregnancy. CONCLUSIONS: When goats were exposed to a dog during pregnancy, their heart rate, blood pressure, and plasma cortisol increased, in contrast to lactation when only their blood pressure and plasma cortisol increased. However, when they were lactating, goats vocalized more and started to ruminate later compared to when they were pregnant. PMID- 22087735 TI - Si nanowires by a single-step metal-assisted chemical etching process on lithographically defined areas: formation kinetics. AB - In this paper, we investigate the formation kinetics of Si nanowires [SiNWs] on lithographically defined areas using a single-step metal-assisted chemical etching process in an aqueous HF/AgNO3 solution. We show that the etch rate of Si, and consequently, the SiNW length, is much higher on the lithographically defined areas compared with that on the non-patterned areas. A comparative study of the etch rate in the two cases under the same experimental conditions showed that this effect is much more pronounced at the beginning of the etching process. Moreover, it was found that in both cases, the nanowire formation rate is linear with temperature in the range from 20 degrees C to 50 degrees C, with almost the same activation energy, as obtained from an Arrhenius plot (0.37 eV in the case of non-patterned areas, while 0.38 eV in the case of lithographically patterned areas). The higher etch rate on lithographically defined areas is mainly attributed to Si surface modification during the photolithographic process.PACS: 68; 68.65-k. PMID- 22087736 TI - Self-assessment and objective determination of dexterity in patients with type 1 or type 2 diabetes mellitus. AB - OBJECTIVE: Insulin-treated patients perform complex treatment activities during daily routine, such as blood glucose measurements and insulin injections. We aimed to identify suitable dexterity and cognitive function tests for diabetes patients, and to compare the patient self-assessment of their dexterity skills with the test results (Jebsen-Taylor hand function test, (JHFT), motoric performance test (MLS), number connection test). METHOD: We enrolled 90 diabetes patients (36 females, 54 males): 15 type 1 with clinically suspected dexterity impairment (A: age: 60 +/- 9 years), 30 type 2 with clinically suspected dexterity impairment (B: 61 +/- 10 years), 30 type 1 or type 2 patients with visual impairment (C: 64 +/- 6 years), and 15 type 1 or type 2 patients without obvious impairment (control group: D: 64 +/- 5 years). RESULTS: There were no differences regarding neuropathy and slight impairments in the number connection test in all groups. Patient self-assessment revealed that 33.4% in group A, 33.3% in group B, 36.7% in group C and 13.7% in group D, considered themselves to have dexterity impairment. However in the JHFT test, all patients from A (100%) and B (100%), 33% from C, and 0% from D presented with dexterity impairment by only passing less than four subtests. CONCLUSIONS: Impairment of dexterity was much more frequent than believed by the patients themselves. It may be worthwhile to consider these findings when classifying patients regarding their capabilities to perform certain treatments or when assessing diabetes technology with human subjects. PMID- 22087742 TI - The quantitative analysis of thiamin and riboflavin and their respective vitamers in fermented alcoholic beverages. AB - This research aimed to develop a simple and effective method for analyzing thiamin (B(1)), riboflavin (B(2)) and their respective vitamers by high performance liquid chromatography (HPLC) in fermented alcoholic beverages. The method developed here employs a phosphate buffer/methanol gradient elution on a single reverse phase column, coupled with independent fluorescent detection regimes. It also employs a precolumn derivatization to convert thiamin to thiochrome via an alkaline potassium ferricyanide solution. The method described here allowed a spike recovery of better than 97%, with a typical linear detection range (R(2) >= 0.9997) between <= 5 and >= 500 MUg/L for all vitamers studied. Lager style beers were found to contain significantly (p < 0.001) less thiamin than other tested styles of beers (lager, 35.7 MUg/L; ale, 88.3 MUg/L; stout/porters, 104.4 MUg/L; wheat beers, 130.7 MUg/L), which may be due to the raw material and extensive processing that occurs for this style. There was no statistical difference (p = 0.608) between the riboflavin content of each beer style. Furthermore, wines and ciders contain less thiamin and riboflavin than beer, which is also likely to be due to the base materials used and the differences in processing steps to produce these beverages. PMID- 22087737 TI - ReCount: a multi-experiment resource of analysis-ready RNA-seq gene count datasets. AB - BACKGROUND: RNA sequencing is a flexible and powerful new approach for measuring gene, exon, or isoform expression. To maximize the utility of RNA sequencing data, new statistical methods are needed for clustering, differential expression, and other analyses. A major barrier to the development of new statistical methods is the lack of RNA sequencing datasets that can be easily obtained and analyzed in common statistical software packages such as R. To speed up the development process, we have created a resource of analysis-ready RNA-sequencing datasets. 2 DESCRIPTION: ReCount is an online resource of RNA-seq gene count tables and auxilliary data. Tables were built from raw RNA sequencing data from 18 different published studies comprising 475 samples and over 8 billion reads. Using the Myrna package, reads were aligned, overlapped with gene models and tabulated into gene-by-sample count tables that are ready for statistical analysis. Count tables and phenotype data were combined into Bioconductor ExpressionSet objects for ease of analysis. ReCount also contains the Myrna manifest files and R source code used to process the samples, allowing statistical and computational scientists to consider alternative parameter values. 3 CONCLUSIONS: By combining datasets from many studies and providing data that has already been processed from. fastq format into ready-to-use. RData and. txt files, ReCount facilitates analysis and methods development for RNA-seq count data. We anticipate that ReCount will also be useful for investigators who wish to consider cross-study comparisons and alternative normalization strategies for RNA-seq. PMID- 22087738 TI - Are we moving in the right direction with osteoarthritis drug discovery? AB - INTRODUCTION: The success of targeted biologic therapy against rheumatoid arthritis has meant that much research has been devoted to investigating the pathophysiology of osteoarthritis, in the hope of defining novel therapeutic targets. Osteoarthritis has long been thought of mainly as a degenerative disease of cartilage, with secondary bony damage and osteophytes. However, in recent years, the importance of the synovium, and in particular the synovial macrophages, has been highlighted in both in vitro and in vivo studies. AREAS COVERED: The recent progress in osteoarthritis drug discovery, particularly with regard to the search for therapeutic targets for this disease and the development of disease-modifying anti-osteoarthritic drugs is critically assessed. Some important recent research with regard to possible therapeutic targets in osteoarthritis drug discovery is highlighted. EXPERT OPINION: The concept that synovial macrophages and macrophage-produced cytokines, may play a role in driving inflammatory and destructive signalling pathways in osteoarthritis, is of importance for drug discovery in this disease, in spite of disappointing results from early studies of anti-cytokine strategies in osteoarthritis clinical trials. There is also an abundance of potential downstream therapeutic targets in osteoarthritis, including the matrix metalloproteinases, the aggrecanases, iNOS and elements of the Wnt pathway. PMID- 22087740 TI - Stretching and breaking of ultrathin MoS2. AB - We report on measurements of the stiffness and breaking strength of monolayer MoS(2), a new semiconducting analogue of graphene. Single and bilayer MoS(2) is exfoliated from bulk and transferred to a substrate containing an array of microfabricated circular holes. The resulting suspended, free-standing membranes are deformed and eventually broken using an atomic force microscope. We find that the in-plane stiffness of monolayer MoS(2) is 180 +/- 60 Nm(-1), corresponding to an effective Young's modulus of 270 +/- 100 GPa, which is comparable to that of steel. Breaking occurs at an effective strain between 6 and 11% with the average breaking strength of 15 +/- 3 Nm(-1) (23 GPa). The strength of strongest monolayer membranes is 11% of its Young's modulus, corresponding to the upper theoretical limit which indicates that the material can be highly crystalline and almost defect-free. Our results show that monolayer MoS(2) could be suitable for a variety of applications such as reinforcing elements in composites and for fabrication of flexible electronic devices. PMID- 22087743 TI - New family of silver(I) complexes based on hydroxyl and carboxyl groups decorated arenesulfonic acid: syntheses, structures, and luminescent properties. AB - Self-assembly of silver(I) salts and three ortho-hydroxyl and carboxyl groups decorated arenesulfonic acids affords the formation of nine silver(I)-sulfonates, (NH(4)).[Ag(HL1)(NH(3))(H(2)O)] (1), {(NH(4)).[Ag(3)(HL1)(2)(NH(3))(H(2)O)]}(n) (2), [Ag(2)(HL1)(H(2)O)(2)](n) (3), [Ag(2)(HL2)(NH(3))(2)].H(2)O (4), [Ag(H(2)L2)(H(2)O)](n) (5), [Ag(2)(HL2)](n) (6), [Ag(3)(L3)(NH(3))(3)](n) (7), [Ag(2)(HL3)](n) (8), and [Ag(6)(L3)(2)(H(2)O)(3)](n) (9) (H(3)L1 = 2-hydroxyl-3 carboxyl-5-bromobenzenesulfonic acid, H(3)L2 = 2-hydroxyl-4 carboxylbenzenesulfonic acid, H(3)L3 = 2-hydroxyl-5-carboxylbenzenesulfonic acid), which are characterized by elemental analysis, IR, TGA, PL, and single crystal X-ray diffraction. Complex 1 is 3-D supramolecular network extended by [Ag(HL1)(NH(3))(H(2)O)](-) anions and NH(4)(+) cations. Complex 2 exhibits 3-D host-guest framework which encapsulates ammonium cations as guests. Complex 3 presents 2-D layer structure constructed from 1-D tape of sulfonate-bridged Ag1 dimers linked by [(Ag2)(2)(COO)(2)] binuclear units. Complex 4 exhibits 3-D hydrogen-bonding host-guest network which encapsulates water molecules as guests. Complex 5 shows 3-D hybrid framework constructed from organic linker bridged 1-D Ag-O-S chains while complex 6 is 3-D pillared layered framework with the inorganic substructure constructing from the Ag2 polyhedral chains interlinked by Ag1 dimers and sulfonate tetrahedra. The hybrid 3-D framework of complex 7 is formed by L3(-) trianions bridging short trisilver(I) sticks and silver(I) chains. Complex 8 also presents 3-D pillared layered framework, and the inorganic layer substructure is formed by the sulfonate tetrahedrons bridging [(Ag1O(4))(2)(Ag2O(5))(2)](infinity) motifs. Complex 9 represents the first silver-based metal-polyhedral framework containing four kinds of coordination spheres with low coordination numbers. The structural diversities and evolutions can be attributed to the synthetic methods, different ligands and coordination modes of the three functional groups, that is, sulfonate, hydroxyl and carboxyl groups. The luminescent properties of the nine complexes have also been investigated at room temperature, especially, complex 1 presents excellent blue luminescence and can sensitize Tb(III) ion to exhibit characteristic green emission. PMID- 22087739 TI - A systematic review of musculoskeletal disorders among school teachers. AB - BACKGROUND: Musculoskeletal disorders (MSD) represent one of the most common and most expensive occupational health problems in both developed and developing countries. School teachers represent an occupational group among which there appears to be a high prevalence of MSD. Given that causes of MSD have been described as multi-factorial and prevalence rates vary between body sites and location of study, the objective of this systematic review was to investigate the prevalence and risk factors for MSD among teaching staff. METHODS: The study involved an extensive search of MEDLINE and EMBASE databases in 2011. All studies which reported on the prevalence and/or risk factors for MSD in the teaching profession were initially selected for inclusion. Reference lists of articles identified in the original search were then examined for additional publications. Of the 80 articles initially located, a final group of 33 met the inclusion criteria and were examined in detail. RESULTS: This review suggests that the prevalence of self-reported MSD among school teachers ranges between 39% and 95%. The most prevalent body sites appear to be the back, neck and upper limbs. Nursery school teachers appear to be more likely to report suffering from low back pain. Factors such as gender, age, length of employment and awkward posture have been associated with higher MSD prevalence rates. CONCLUSION: Overall, this study suggests that school teachers are at a high risk of MSD. Further research, preferably longitudinal, is required to more thoroughly investigate the issue of MSD among teachers, with a greater emphasis on the possible wider use of ergonomic principles. This would represent a major step forward in the prevention of MSD among teachers, especially if easy to implement control measures could be recommended. PMID- 22087744 TI - Toward a mechanistic understanding of exciton-mediated hydrosilylation on nanocrystalline silicon. AB - White-light initiated hydrosilylation of nanocrystalline porous silicon was found to be far more efficient (in terms of both kinetics and yield) in the presence of electron-accepting molecules with suitably high reduction potentials, particularly halocarbons. It is known that absorption of visible light by nanocrystalline silicon results in the formation of excitons (electron/hole pairs) and that this exciton can be harnessed to drive a hydrosilylation reaction with an alkene; the Si-C bond forms as a result of attack of the pi-electrons of the alkene on the positively charged holes. In order to better understand the white-light initiated mechanism through which this reaction takes place, and to compare with UV-mediated photoemission on Si(111)-H, a series of electron acceptors were screened for their effect on surface alkene hydrosilylation. A very strong correlation between reduction potentials (E(red)) of the oxidant and reaction efficiency was observed, with a minimum "turn-on" E(red) required for an increase to take place. The oxidant appears to accept, or remove, the electron from the nanocrystallite-bound exciton, favoring attack by the alkene on the positively charged Si nanocrystallite, leading to Si-C bond formation. Radical reactions were discounted for a number of reasons, including lack of effect of radical traps, no apparent Si-Cl bond formation, lack of oxidation of the surfaces, and others. Unlike with other oxidants such as nitro-aromatics, halocarbons do not cause additional surface reactions and promote very clean, fast, and selective hydrosilylation chemistry. PMID- 22087741 TI - Ionizing radiation increases adhesiveness of human aortic endothelial cells via a chemokine-dependent mechanism. AB - Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. Since radiation also induces inflammation, a possible mechanism is a change in the adhesiveness of vascular endothelial cells, triggering pro-atherogenic accumulation of leukocytes. To investigate this mechanism at the cellular level, the effect of X rays on adhesiveness of cultured human aortic endothelial cells (HAECs) was determined. HAECs were grown as monolayers and exposed to 0 to 30 Gy X rays, followed by measurement of adhesiveness under physiological shear stress using a flow chamber adhesion assay. Twenty-four hours after irradiation, HAEC adhesiveness was increased, with a peak effect at 15 Gy. Radiation had no significant effect on surface expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Antibody blockade of the leukocyte integrin receptors for ICAM-1 and VCAM-1, however, abolished the radiation-induced adhesiveness. Since these leukocyte integrins can be activated by chemokines presented on the endothelial cell surface, the effect of pertussis toxin (PTX), an inhibitor of chemokine-mediated integrin activation, was tested. PTX specifically inhibited radiation-induced adhesiveness, with no significant effect on nonirradiated cells. Therefore, radiation induces increased adhesiveness of aortic endothelial cells through chemokine-dependent signaling from endothelial cells to leukocytes, even in the absence of increased expression of the adhesion molecules involved. PMID- 22087734 TI - Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration. AB - INTRODUCTION: Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-alpha inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-beta1 (TGF beta1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-alpha suppress, while TGF-beta1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair. METHODS: A micro-wound assay was used to assess meniscal cell migration and proliferation in response to the following treatments for 0, 24, or 48 hours: 0 to 10 ng/mL IL-1, TNF-alpha, or TGF-beta1, in the presence or absence of 10% serum. Proliferated and total cells were fluorescently labeled and imaged using confocal laser scanning microscopy and the number of proliferated, migrated, and total cells was determined in the micro wound and edges of each image. Meniscal cell proliferation was also assessed throughout meniscal repair model explants treated with 0 or 10 ng/mL IL-1, TNF alpha, or TGF-beta1 for 14 days. At the end of the culture period, biomechanical testing and histological analyses were also performed. Statistical differences were assessed using an ANOVA and Newman-Keuls post hoc test. RESULTS: IL-1 and TNF-alpha decreased cell proliferation in both cell and tissue models of meniscal repair. In the presence of serum, TGF-beta1 increased outer zone cell proliferation in the micro-wound and in the cross section of meniscal repair model explants. Both IL-1 and TNF-alpha decreased the integrative shear strength of repair and extracellular matrix deposition in the meniscal repair model system, while TGF-beta1 had no effect on either measure. CONCLUSIONS: Meniscal cell proliferation in vivo may be diminished following joint injury due to the up regulation of inflammatory cytokines, thereby limiting native cellular repair of meniscal lesions. Therefore, therapies that can promote meniscal cell proliferation have promise to enhance meniscal repair and improve tissue engineering strategies. PMID- 22087751 TI - Check dam in the Loess Plateau of China: engineering for environmental services and food security. PMID- 22087752 TI - Fluorescence dynamics and dipole moment evolution of singlet exciton decay in conjugated polymers. AB - Both fluorescence dynamics and time-dependent electron transitions are introduced within a previously developed molecule dynamics approach for treating conjugated polymers. This is able to provide a panoramic view of luminescence dynamics during singlet exciton decay, in which the fluorescence dynamics is largely determined by the electron population and the evolution of the dipole moment. The fluorescence intensity is weakened due to a reduced dipole moment and diminished decay rate of the electron, which validates a previous assumption based on experimental studies. The lifetime of the singlet exciton in a conjugated polymer is found to be 1.2 ns, and the calculated time profile of the fluorescence intensity is in agreement with recent experimental results. PMID- 22087750 TI - Discovery of potent and highly selective thienopyridine Janus kinase 2 inhibitors. AB - Developing Janus kinase 2 (Jak2) inhibitors has become a significant focus for small molecule drug discovery programs in recent years due to the identification of a Jak2 gain-of-function mutation in the majority of patients with myeloproliferative disorders (MPD). Here, we describe the discovery of a thienopyridine series of Jak2 inhibitors that culminates with compounds showing 100- to >500-fold selectivity over the related Jak family kinases in enzyme assays. Selectivity for Jak2 was also observed in TEL-Jak cellular assays, as well as in cytokine-stimulated peripheral blood mononuclear cell (PBMC) and whole blood assays. X-ray cocrystal structures of 8 and 19 bound to the Jak2 kinase domain aided structure-activity relationship efforts and, along with a previously reported small molecule X-ray cocrystal structure of the Jak1 kinase domain, provided structural rationale for the observed high levels of Jak2 selectivity. PMID- 22087745 TI - Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens. AB - BACKGROUND: To develop effective strategies in cancer chemoprevention, an increased understanding of endogenous biochemical mediators that block metastatic processes is critically needed. Dietary lipids and non-steroidal anti inflammatory drugs (NSAIDs) have a published track record of providing protection against gastrointestinal malignancies. In this regard, we examined the effects of membrane plasmalogens and ibuprofen on regulation of cellular levels of diamines, polyamine mediators that are augmented in cancer cells. For these studies we utilized Chinese hamster ovary (CHO) cells and NRel-4 cells, a CHO cell line with defective plasmalogen synthesis. RESULTS: NRel-4 cells, which possess cellular plasmalogen levels that are 10% of control CHO cells, demonstrated 2- to 3-fold increases in cellular diamine levels. These diamine levels were normalized by plasmalogen replacement and significantly reduced by ibuprofen. In both cases the mechanism of action appears to mainly involve increased diamine efflux via the diamine exporter. The actions of ibuprofen were not stereospecific, supporting previous studies that cyclooxygenase (COX) inhibition is unlikely to be involved in the ability of NSAIDs to reduce intracellular diamine levels. CONCLUSIONS: Our data demonstrate that ibuprofen, a drug known to reduce the risk of colorectal cancer, reduces cellular diamine levels via augmentation of diamine efflux. Similarly, augmentation of membrane plasmalogens can increase diamine export from control and plasmalogen-deficient cells. These data support the concept that membrane transporter function may be a therapeutic point of intervention for dietary and pharmacological approaches to cancer chemoprevention. PMID- 22087753 TI - The decarboxylative Strecker reaction. AB - alpha-Amino acids react with aldehydes in the presence of a cyanide source to form alpha-amino nitriles in what can be considered a decarboxylative variant of the classical Strecker reaction. This unprecedented transformation does not require the use of a metal catalyst and provides facile access to valuable alpha amino nitriles that are inaccessible by traditional Strecker chemistry. PMID- 22087756 TI - Characterization of C5 hydrocarbons relevant to catalysis. AB - A recent in situ infrared study on the selective hydrogenation of C5 dienes and monoenes over a Pd/Al(2)O(3) catalyst only reported incomplete vibrational assignments for some of the reagents, intermediates, and products encountered in that study. This work uses a combination of infrared absorption spectroscopy, Raman, and inelastic neutron scattering to characterize the vibrational spectra of pentane, 1-pentene, cis- and trans-2-pentene, cis- and trans-1,3-pentadiene, 1,4-pentadiene, cyclopentane, and cyclopentene. Ab initio calculations of the potential energy surface, geometry, and vibrational transition energies were performed and simulations of the vibrational spectra compared to the experimental data. Complete vibrational assignments for the majority of the molecules are presented. The potential for using gas-phase infrared measurements for studying heterogeneously catalyzed gas-phase reactions is also briefly considered. PMID- 22087755 TI - Application of the Andersen's health care utilization framework to secondary complications of spinal cord injury: a scoping review. AB - PURPOSE: The purpose of this scoping review was to identify research priority areas related to secondary complications and associated health care use for individuals with spinal cord injury (SCI). METHOD: DATA SOURCES: Peer-reviewed journals were identified using CINAHL, MEDLINE, PubMed, Embase, Social Sciences Abstracts, Social Works Abstract and PsycInfo search engines. Key references were hand searched. STUDY SELECTION: A total of 289 abstracts were identified from the initial search strategy. We removed studies that did not measure health care and those that did not involve analytical investigation. DATA EXTRACTION: The selected 31 studies were reviewed in detail using a coding template based on the domains and sub-components of the Andersen model (i.e. environmental, population characteristics, health behavior and outcome). RESULTS: Most studies measured predisposing characteristics (e.g., age, gender) and need characteristics (e.g., level of injury). There was a notable absence of environmental characteristics (e.g., health system, neighborhood variables), enabling characteristics and health behaviors (beyond diet and nutrition). CONCLUSIONS: We identified a gap in the SCI literature. Future research should focus on longitudinal study designs with more representation of non-traumatic spinal cord injury, as well as utilizing more advanced statistical analyses (i.e., multivariate level) to adjust for confounding variables. PMID- 22087754 TI - Exposure to repetitive tasks induces motor changes related to skill acquisition and inflammation in rats. AB - The authors elucidate exposure-response relationships between repetitive tasks, inflammation, and motor changes with work-related musculoskeletal disorders. Using a rat model of reaching and handle pulling, they examined effects of performing a high-repetition, low-force (HRLF); low-repetition, high-force (LRHF); or high-repetition, high-force (HRHF) task (2 hr/day, 3 days/week, 12 weeks) on reach rate and force, percentage of successful reaches, duration of participation, and grip strength. Reach rate and reach force improved with HRLF, and percentage success increased in all groups in Week 9, and in HRLF and HRHF in Week 12, indicative of skill acquisition. Duration and grip strength showed force dependent declines with task performance. A subset of HRHF rats received ibuprofen in Weeks 5-12. Ibuprofen significantly improved reach rate, reach force, and duration in treated rats, indicative of an inflammatory influence on reach performance. Ibuprofen improved percentage of successful reaches in Week 9, although this increase was not sustained. However, declines in grip strength, a nocifensive behavior, were not prevented by ibuprofen. Examination of cervical spinal cords of untreated and ibuprofen treated HRHF rats showed increased IL 1beta, an inflammatory cytokine, in neurons. These findings suggest that only a preventive intervention could have addressed all motor declines. PMID- 22087757 TI - Evaluation of chronic lymphocytic leukemia by oligonucleotide-based microarray analysis uncovers novel aberrations not detected by FISH or cytogenetic analysis. AB - BACKGROUND: Cytogenetic evaluation is a key component of the diagnosis and prognosis of chronic lymphocytic leukemia (CLL). We performed oligonucleotide based comparative genomic hybridization microarray analysis on 34 samples with CLL and known abnormal karyotypes previously determined by cytogenetics and/or fluorescence in situ hybridization (FISH). RESULTS: Using a custom designed microarray that targets >1800 genes involved in hematologic disease and other malignancies, we identified additional cryptic aberrations and novel findings in 59% of cases. These included gains and losses of genes associated with cell cycle regulation, apoptosis and susceptibility loci on 3p21.31, 5q35.2q35.3, 10q23.31q23.33, 11q22.3, and 22q11.23. CONCLUSIONS: Our results show that microarray analysis will detect known aberrations, including microscopic and cryptic alterations. In addition, novel genomic changes will be uncovered that may become important prognostic predictors or treatment targets for CLL in the future. PMID- 22087758 TI - Single nucleotide polymorphisms associated with risk for contralateral breast cancer in the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study. AB - INTRODUCTION: Genome-wide association studies, focusing primarily on unilateral breast cancer, have identified single nucleotide polymorphisms (SNPs) in a number of genomic regions that have alleles associated with a significantly increased risk of breast cancer. In the current study we evaluate the contributions of these previously identified regions to the risk of developing contralateral breast cancer. The most strongly disease-associated SNPs from prior studies were tested for association with contralateral breast cancer. A subset of these SNPs, selected upon their main effects on contralateral breast cancer risk was further evaluated for interaction with treatment modalities and estrogen receptor (ER) status. METHODS: We genotyped 21 SNPs in 708 women with contralateral breast cancer and 1394 women with unilateral breast cancer who serve as the cases and controls in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study. Records of treatment and ER status were available for most of WECARE Study participants. Associations of SNP genotypes and risk for contralateral breast cancer were calculated with multivariable adjusted conditional logistic regression methods. RESULTS: Multiple SNPs in the FGFR2 locus were significantly associated with contralateral breast cancer, including rs1219648 (per allele rate ratio (RR) = 1.25, 95%CI = 1.08-1.45). Statistically significant associations with contralateral breast cancer were also observed at rs7313833, near the PTHLH gene (per allele RR = 1.26, 95%CI = 1.08-1.47), rs13387042 (2q35) (per allele RR = 1.19, 95%CI = 1.02-1.37), rs13281615 (8q24) (per allele RR = 1.21, 95%CI = 1.04 1.40), and rs11235127 near TMEM135 (per allele RR = 1.26, 95%CI = 1.04-1.53). The A allele of rs13387042 (2q35) was significantly associated with contralateral breast cancer in ER negative first tumors while the A allele of rs11235127 (near TMEM135) was significantly associated with contralateral breast cancer in ER positive first tumors. Although some SNP genotypes appeared to modify contralateral breast cancer risk with respect to tamoxifen treatment or particular radiation doses, trend tests for such effects were not significant. CONCLUSIONS: Our results indicate that some common risk variants associated with primary breast cancer also increase risk for contralateral breast cancer, and that these risks vary with the ER status of the first tumor. PMID- 22087759 TI - Peripheral leukocyte counts and outcomes after intracerebral hemorrhage. AB - BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating disease that carries a 30 day mortality of approximately 45%. Only 20% of survivors return to independent function at 6 months. The role of inflammation in the pathophysiology of ICH is increasingly recognized. Several clinical studies have demonstrated an association between inflammatory markers and outcomes after ICH; however the relationship between serum biomarkers and functional outcomes amongst survivors has not been previously evaluated. Activation of the inflammatory response as measured by change in peripheral leukocyte count was examined and assessment of mortality and functional outcomes after ICH was determined. FINDINGS: Patients with spontaneous ICH admitted to a tertiary care center between January 2005 and April 2010 were included. The change in leukocyte count was measured as the difference between the maximum leukocyte count in the first 72 hours and the leukocyte count on admission. Mortality was the primary outcome. Secondary outcomes were mortality at 1 year, discharge disposition and the modified Barthel index (MBI) at 3 months compared to pre-admission MBI. 423 cases were included. The in-hospital mortality was 30.4%. The change in leukocyte count predicted worse discharge disposition (OR = 1.258, p = 0.009). The change in leukocyte count was also significantly correlated with a decline in the MBI at 3 months. These relationships remained even after removal of all patients with evidence of infection. CONCLUSIONS: Greater changes in leukocyte count over the first 72 hours after admission predicted both worse short term and long term functional outcomes after ICH. PMID- 22087760 TI - Self-microemulsifying smaller molecular volume oil (Capmul MCM) using non-ionic surfactants: a delivery system for poorly water-soluble drug. AB - The main purpose of this work is to formulate self-microemulsifying drug delivery system (SMEDDS) using smaller molecular oil with Atorvastatin calcium as a model drug. Solubility of the selected drug was accessed in oils and surfactants. Percent transmittance (%T) test study was performed to identify the efficient self-microemulsifying formulations. Those formulations which showed higher value for %T were evaluated for droplet size, polydispersity index, zeta potential, refractive index and cloud point measurement. Effect of drug loading on droplet size, increasing dilution in different media, thermodynamic stability and in vitro dissolution was performed to observe the performance of the selected formulation. Further cytotoxicity and permeation enhancement studies were carried out on Caco2 cell lines. Of all the oils accessed for drug solubility, Capmul MCM showed higher solubility capacity for Atorvastatin calcium. Capmul MCM was better microemulsified using combination of Tween 20 and Labrasol surfactant. Droplet size was as low as 86.93 nm with polydispersity index and zeta potential at 0.195 +/- 0.011 and -7.27 +/- 3.11 mV respectively. The selected undiluted formulation showed refractive index values ranging from 1.40 to 1.47 indicating the isotropicity of the formulation. The selected formulation was robust to dilution in different media and thermodynamically stable. Dissolution profile was enhanced for the selected drug as compared to marketed formulation with t85% and DE values at 10 min and 80.15 respectively. Also cytotoxicity measurement showed minimum effect with good permeation enhancing capacity. Thus our study demonstrates the use of smaller molecular oil (Capmul MCM) for developing self-microemulsifying drug delivery system for better in vitro and in vivo performance. PMID- 22087761 TI - Improving gene expression data interpretation by finding latent factors that co regulate gene modules with clinical factors. AB - BACKGROUND: In the analysis of high-throughput data with a clinical outcome, researchers mostly focus on genes/proteins that show first-order relations with the clinical outcome. While this approach yields biomarkers and biological mechanisms that are easily interpretable, it may miss information that is important to the understanding of disease mechanism and/or treatment response. Here we test the hypothesis that unobserved factors can be mobilized by the living system to coordinate the response to the clinical factors. RESULTS: We developed a computational method named Guided Latent Factor Discovery (GLFD) to identify hidden factors that act in combination with the observed clinical factors to control gene modules. In simulation studies, the method recovered masked factors effectively. Using real microarray data, we demonstrate that the method identifies latent factors that are biologically relevant, and extracts more information than analyzing only the first-order response to the clinical outcome. CONCLUSIONS: Finding latent factors using GLFD brings extra insight into the mechanisms of the disease/drug response. The R code of the method is available at http://userwww.service.emory.edu/~tyu8/GLFD. PMID- 22087762 TI - Beetroot betalain inhibits peroxynitrite-mediated tyrosine nitration and DNA strand cleavage. AB - Two major betalains, red-purple betacyanins and yellow betaxanthins, were isolated from red beetroots (Beta vulgaris L.), and their peroxynitrite (ONOO(-)) scavenging capacity was investigated. Apparent colours of the betalains were bleached by the addition of ONOO(-), and the absorbance decreases were suppressed in the presence of glutathione, a ONOO(-) scavenger. After bleaching, a new absorption maximum was observed at 350 nm in the spectrum of the resulting reaction mixture. New peaks were detected from HPLC analysis of the reaction products of betanin, a representative constituent of red beetroot betacyanins, treated with ONOO(-) monitoring at 350 nm, and the intensity of the major peak was positively correlated with ONOO(-) concentration. Betanin inhibited the ONOO( ) (0.5 mM)-dependent nitration of tyrosine (0.1 mM). Additionally, the IC(50) value of betanin (19.2 MUM) was lower than that of ascorbate (79.6 MUM). The presence of betanin (0.05-1.0 mM) also inhibited ONOO(-) (0.5 mM)-dependent DNA strand cleavage in a concentration-dependent manner. These results suggest that betalains can protect cells from nitrosative stress in addition to protecting them from oxidative stresses. PMID- 22087763 TI - Differential signalling through ALK-1 and ALK-5 regulates leptin expression in mesenchymal stem cells. AB - Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little is known about its expression mechanism. Leptin is often described as adipokine, while it is expressed by other cell types. We have recently shown an in vitro leptin expression, enhanced by glucocorticoids in synovial fibroblasts (SVF). Here, we investigated leptin expression in MSC from bone marrow (BM-MSC) and umbilical cord matrix (UMSC). Results showed that BM-MSC, but not UMSC, expressed leptin that was strongly enhanced by glucocorticoids. Transforming growth factor beta1 (TGF-beta1) markedly inhibited the endogenous- and glucocorticoid-induced leptin expression in BM-MSC. Since TGF-beta1 was shown to signal via ALK-5-Smad2/3 and/or ALK-1-Smad1/5 pathways, we analyzed the expression of proteins from both pathways. In BM-MSC, TGF-beta1 increased phosphorylated Smad2 (p-Smad2) expression, while ALK-5 inhibitor (SB431542) induced leptin expression and significantly restored TGF-beta1-induced leptin inhibition. In addition, both prednisolone and SB431542 increased p-Smad1/5 expression. These results suggested the ALK-5-Smad2 pathway as an inhibitor of leptin expression, while ALK-1-Smad1/5 as an activator. Indeed, Smad1 expression silencing induced leptin expression inhibition. Furthermore, prednisolone enhanced the expression of TGF-betaRII while decreasing p-Smad2 in BM-MSC and SVF but not in UMSC. In vitro differentiation revealed differential osteogenic potential in SVF, BM-MSC, and UMSC that was correlated to their leptin expression potential. Our results suggest that ALK-1/ALK-5 balance regulates leptin expression in MSC. It also underlines UMSC as leptin nonproducer MSC for cell therapy protocols where leptin expression is not suitable. PMID- 22087764 TI - Overlapping distribution of osteopontin and calcium in the ischemic core of rat brain after transient focal ischemia. AB - Osteopontin (OPN), an adhesive glycoprotein, has recently been proposed to act as an opsonin that facilitates phagocytosis of neuronal debris by macrophages in the ischemic brain. The present study was designed to elucidate the process whereby OPN binds to neuronal cell debris in a rat model of ischemic stroke. Significant co-localization of the OPN protein and calcium deposits in the ischemic core were observed by combining alizarin red staining and OPN immunohistochemistry. In addition, electron microscopy (EM) using the osmium/potassium dichromate method revealed that electron-dense precipitates, typical of calcium deposits, were localized mainly along the periphery of putative degenerating neurites. This topical pattern of calcium precipitates resembled the distribution of OPN as detected by immunogold-silver EM. Combining immunogold-silver EM and electron probe microanalysis further demonstrated that the OPN protein was localized at the periphery of cell debris or degenerating neurites, corresponding with locally higher concentrations of calcium and phosphorus, and that the relative magnitude of OPN accumulation was comparable to that of calcium and phosphorus. These data suggest that calcium precipitation provides a matrix for the binding of the OPN protein within the debris or degenerating neurites induced by ischemic injury. Therefore, OPN binding to calcium deposits may be involved in phagocytosis of such debris, and may participate in the regulation of ectopic calcification in the ischemic brain. PMID- 22087767 TI - Overoxidation of phenol by hexachloroiridate(IV). AB - It has been previously established that the aqueous oxidation of phenol by a deficiency of [IrCl(6)](2-) proceeds through the production of [IrCl(6)](3-) and phenoxyl radicals. Coupling of the phenoxyl radicals leads primarily to 4,4' biphenol, 2,2'-biphenol, 2,4'-biphenol, and 4-phenoxyphenol. Overoxidation occurs through the further oxidation of these coupling products, leading to a rather complex mixture of final products. The rate laws for oxidation of the four coupling products by [IrCl(6)](2-) have the same form as those for the oxidation of phenol itself: -d[Ir(IV)]/dt = {(k(ArOH) + k(ArO(-))K(a)/[H(+)])/(1 + K(a)/[H(+)])}[ArOH](tot)[Ir(IV)]. Values for k(ArOH) and k(ArO(-)) have been determined for the four substrates at 25 degrees C and are assigned to H(2)O PCET and electron-transfer mechanisms, respectively. Kinetic simulations of a combined mechanism that includes the rate of oxidation of phenol as well as the rates of these overoxidation steps show that the degree of overoxidation is rather limited at high pH but quite extensive at low pH. This pH-dependent overoxidation leads to a pH-dependent stoichiometric factor in the rate law for oxidation of phenol and causes some minor deviations in the rate law for oxidation of phenol. Empirically, these minor deviations can be accommodated by the introduction of a third term in the rate law that includes a "pH-dependent rate constant", but this approach masks the mechanistic origins of the effect. PMID- 22087766 TI - 'It brought joy in my home as in the area of my wife.' How recently circumcised adult men ascribe value to and make sense of male circumcision. AB - The present study used a phenomenological approach to explore the everyday-life experiences of male circumcision (MC) and to learn how recently circumcised men ascribe value to and make sense of MC. Thirteen recently circumcised Zambian men were identified through the snowball technique and interviewed using a semi structured interviewer's guide. Findings indicate that the post-operational experience of adult MC smoothly fits into the everyday-life experience of the men interviewed and is perceived and experienced as a broader social health issue, which largely transcends both the personal HIV risk of the individual male and the private sphere. The study provides three important lessons for MC programmes: (1) the broad social aspects of MC put forward by the interviewees suggest the potential for a popular intervention and, consequently, a large uptake of MC; (2) findings suggest that in addition to emphasising the HIV protective effect of MC, MC promotion should also highlight the social, sexual and romantic values perceived and experienced by the interviewees of this study; (3) the analysis reveals potentially harmful misconceptions about the health benefits of MC, demonstrating the importance of proper pre- and post-circumcision counselling as well as public health messages related to MC. PMID- 22087765 TI - Construction of permanently inducible miRNA-based expression vectors using site specific recombinases. AB - BACKGROUND: RNA interference (RNAi) is a conserved gene silencing mechanism mediated by small inhibitory microRNAs (miRNAs).Promoter-driven miRNA expression vectors have emerged as important tools for delivering natural or artificially designed miRNAs to eukaryotic cells and organisms. Such systems can be used to query the normal or pathogenic functions of natural miRNAs or messenger RNAs, or to therapeutically silence disease genes. RESULTS: As with any molecular cloning procedure, building miRNA-based expression constructs requires a time investment and some molecular biology skills. To improve efficiency and accelerate the construction process, we developed a method to rapidly generate miRNA expression vectors using recombinases instead of more traditional cut-and-paste molecular cloning techniques. In addition to streamlining the construction process, our cloning strategy provides vectors with added versatility. In our system, miRNAs can be constitutively expressed from the U6 promoter, or inducibly expressed by Cre recombinase. We also engineered a built-in mechanism to destroy the vector with Flp recombinase, if desired. Finally, to further simplify the construction process, we developed a software package that automates the prediction and design of optimal miRNA sequences using our system. CONCLUSIONS: We designed and tested a modular system to rapidly clone miRNA expression cassettes. Our strategy reduces the hands-on time required to successfully generate effective constructs, and can be implemented in labs with minimal molecular cloning expertise. This versatile system provides options that permit constitutive or inducible miRNA expression, depending upon the needs of the end user. As such, it has utility for basic or translational applications. PMID- 22087768 TI - Synthesis and molecular recognition studies of the HNK-1 trisaccharide and related oligosaccharides. The specificity of monoclonal anti-HNK-1 antibodies as assessed by surface plasmon resonance and STD NMR. AB - The human natural killer cell carbohydrate, HNK-1, plays function-conducive roles in peripheral nerve regeneration and synaptic plasticity. It is also the target of autoantibodies in polyneuropathies. It is thus important to synthesize structurally related HNK-1 carbohydrates for optimizing its function-conducive roles, and for diagnosis and neutralization of autoantibodies in the fatal Guillain-Barre syndrome. As a first step toward these goals, we have synthesized several HNK-1 carbohydrate derivatives to assess the specificity of monoclonal HNK-1 antibodies from rodents: 2-aminoethyl glycosides of selectively O-sulfated trisaccharide corresponding to the HNK-1 antigen, its nonsulfated analogue, and modified structures containing 3-O-fucosyl or 6-O-sulfo substituents in the N acetylglucosamine residues. These were converted, together with several related oligosaccharides, into biotin-tagged probes to analyze the precise carbohydrate specificity of two anti-HNK-1 antibodies by surface plasmon resonance that revealed a crucial role of the glucuronic acid in antibody binding. The contribution of the different oligosaccharide moieties in the interaction was shown by saturation transfer difference (STD) NMR of the complex consisting of the HNK-1 pentasaccharide and the HNK-1 412 antibody. PMID- 22087775 TI - Forced unbinding of individual urea-aminotriazine supramolecular polymers by atomic force microscopy: a closer look at the potential energy landscape and binding lengths at fixed loading rates. AB - Atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS) was used to study the forced unbinding of quadruple self-complementary hydrogen bonded urea-aminotriazine (UAT) complexes in hexadecane (HD). To elucidate the bond strength of individual linkages the unbinding forces of UAT supramolecular polymers were investigated for the first time. The bond rupture was probed at three different, fixed piezo retraction rates in far from equilibrium conditions. The number of supramolecular bonds (N) between AFM tip and the surface was determined by independent knowledge of the linker length. The observed rupture force of urea-aminotriazine (UAT)-based supramolecular polymer chains was found to decrease with increasing rupture length. The dependence of the most probable rupture force on N was in quantitative agreement with the theory of uncooperative bond rupture for supramolecular linkages switched in series. Experiments with three different, fixed loading rates provided identical values (within the experimental error) for the characteristic bond length x(beta) and the off-rate constant in the absence of force k(off)(f = 0). The value of x(beta) was found to agree with literature data on the hydrogen-bond distance obtained via crystallographic data of the hydrogen-bonded dimer. This work broadens the scope of our previous report showing that relevant parameters of the bond energy landscape can be derived from a single data set of rupture events at a fixed loading rate for supramolecular linkages switched in series. PMID- 22087774 TI - Impact of chronic kidney disease on the presence and severity of aortic stenosis in patients at high risk for coronary artery disease. AB - OBJECTIVE: We evaluated the impact of chronic kidney disease (CKD) on the presence and severity of aortic stenosis (AS) in patients at high risk for coronary artery disease (CAD). METHODS: One hundred and twenty consecutive patients who underwent invasive coronary angiography were enrolled. Aortic valve area (AVA) was calculated by the continuity equation using transthoracic echocardiography, and was normalized by body surface area (AVA index). RESULTS: Among all 120 patients, 78% had CAD, 55% had CKD (stage 3: 81%; stage 4: 19%), and 34% had AS (AVA < 2.0 cm2). Patients with AS were older, more often female, and had a higher frequency of CKD than those without AS, but the prevalence of CAD and most other coexisting conventional risk factors was similar between patients with and without AS. Multivariate linear regression analysis indicated that only CKD and CAD were independent determinants of AVA index with standardized coefficients of -0.37 and -0.28, respectively. When patients were divided into 3 groups (group 1: absence of CKD and CAD, n = 16; group 2: presence of either CKD or CAD, n = 51; and group 3: presence of both CKD and CAD, n = 53), group 3 had the smallest AVA index (1.19 +/- 0.30*# cm2/m2, *p < 0.05 vs. group 1: 1.65 +/- 0.32 cm2/m2, and #p < 0.05 vs. group 2: 1.43 +/- 0.29* cm2/m2) and the highest peak velocity across the aortic valve (1.53 +/- 0.41*# m/sec; *p < 0.05 vs. group 1: 1.28 +/- 0.29 m/sec, and #p < 0.05 vs. group 2: 1.35 +/- 0.27 m/sec). CONCLUSION: CKD, even pre-stage 5 CKD, has a more powerful impact on the presence and severity of AS than other conventional risk factors for atherosclerosis in patients at high risk for CAD. PMID- 22087776 TI - Education in gerontology and geriatrics comes of age. PMID- 22087777 TI - Integrating and evaluating geriatrics in medical school: a novel approach for the challenge. AB - Brown Medical School developed a comprehensive curriculum in which enriched aging content increased from 22 to 80 hours in preclerkship courses and was also added for clerkships, residencies, and nongeriatrician physicians. Innovative evaluation strategies are also described. Highlights include "treasure hunts" in the anatomy laboratory, a Scholarly Concentration in Aging, Schwartz Communication Sessions, a Website of aging-related materials, and a monthly column in the state medical journal. Evaluation includes "tracking" to compute the "dose" of aging content, and "journaling" and focus groups to evaluate students' responses. Integrating geriatrics across a broad range of courses and clinical experiences is feasible. PMID- 22087778 TI - Building psychosocial programming in geriatrics fellowships: a consortium model. AB - Geriatric psychosocial problems are prevalent and significantly affect the physical health and overall well-being of older adults. Geriatrics fellows require psychosocial education, and yet to date, geriatrics fellowship programs have not developed a comprehensive geriatric psychosocial curriculum. Fellowship programs in the New York tristate area collaboratively created the New York Metropolitan Area Consortium to Strengthen Psychosocial Programming in Geriatrics Fellowships in 2007 to address this shortfall. The goal of the Consortium is to develop model educational programs for geriatrics fellows that highlight psychosocial issues affecting elder care, share interinstitutional resources, and energize fellowship program directors and faculty. In 2008, 2009, and 2010, Consortium faculty collaboratively designed and implemented a psychosocial educational conference for geriatrics fellows. Cumulative participation at the conferences included 146 geriatrics fellows from 20 academic institutions taught by interdisciplinary Consortium faculty. Formal evaluations from the participants indicated that the conference: a) positively affected fellows' knowledge of, interest in, and comfort with psychosocial issues; b) would have a positive impact on the quality of care provided to older patients; and c) encouraged valuable interactions with fellows and faculty from other institutions. The Consortium, as an educational model for psychosocial learning, has a positive impact on geriatrics fellowship training and may be replicable in other localities. PMID- 22087779 TI - Prevalence, formation, maintenance, and evaluation of interdisciplinary student aging interest groups. AB - The authors describe the prevalence, formation, maintenance, and evaluation of student aging interest groups. They conducted a cross-sectional electronic survey of the 46 academic medical centers funded by the Donald W. Reynolds Foundation. To evaluate their group of approximately 50 students, the authors conducted an electronic pretest and posttest of attitudes toward interdisciplinary education and knowledge about aging. Twenty-nine of 32 responding institutions funded by the Reynolds Foundation conducted a group; only medical students participated in one half of these groups. Panel presentations were the most prevalent group activity. Evaluation of their group revealed that an interprofessional service learning experience had the greatest impact on student perceptions of the educational preparation and competency of other disciplines. At posttest, medical students in their group had significantly less positive perceptions of actual cooperation between disciplines than did physical therapy or pharmacy students. Aging interest groups conducted by institutions funded by the Reynolds Foundation did not have a high level of interdisciplinary participation. Intermittent exposure to other disciplines during a small number of group activities may be insufficient to overcome "disciplinary split" and achieve interprofessional team orientation without changes in the structure of medical education. PMID- 22087780 TI - Effective teaching methods for geriatric competencies. AB - This study assesses how effective classroom sessions are at teaching geriatric competencies to medical students. At Stony Brook Medical School, most geriatric competencies are taught in the Ambulatory Care Clerkship during small-group educational sessions. Clinical exposure to reinforce these specialized skills varies with preceptor assignment. A student's ability to perform geriatric assessments was evaluated by scores on an Objective Structured Clinical Exam (OSCE) with a geriatric patient. Scores from students who received additional clinical practice of these skills were compared with scores from students who did not. No significant difference in OSCE scores were seen between the two groups. PMID- 22087781 TI - Medical readers' theater: relevance to geriatrics medical education. AB - Medical Readers' Theater (MRT) is an innovative and simple way of helping medical students to reflect on difficult-to-discuss topics in geriatrics medical education, such as aging stereotypes, disability and loss of independence, sexuality, assisted living, relationships with adult children, and end-of-life issues. The authors describe a required MRT experience involving third-year medical students on their Family Medicine clerkship and volunteer residents from a nearby continuing care retirement community. Evaluation of the program shows positive benefits to student and senior participants in terms of greater awareness of each other's perspectives and improved communication. PMID- 22087782 TI - Interest in long-term care among health services administration students. AB - The aging of the population has created increased opportunities for health administrators in long-term care. This study consisted of a cross-sectional survey of 68 undergraduate health services administration students to explore factors related to interest in a career in long-term care administration. One third expressed interest working in the field. Experience in long-term care settings, quality of contact with unrelated older adults, satisfaction working with the elderly, and confidence in the ability to work in the field were positively associated with interest in long-term care administration. The findings have important implications for experiential learning in health administration programs. PMID- 22087783 TI - Evaluation of the person-centered care essentials program: importance of trainers in achieving targeted outcomes. AB - A person-centered care (PCC) training program was developed and disseminated to 84 institutes for retired religious persons across the United States. The program was delivered via a train-the-trainer model wherein institute trainers attended a 2-day training conference, then taught the material to direct care workers (DCWs) at their respective sites. Evaluation of the training showed that DCWs' attitudes toward and knowledge of PCC improved after training. The relationship between trainers' perception of the ability of their site to implement PCC training and DCW knowledge improvement varied by training module. Training regarding the physical environment resulted in the smallest gains in DCW knowledge. PMID- 22087784 TI - Information needs of family caregivers of persons with cognitive versus physical deficits. AB - This study compared information needs of caregivers of persons with dementia with caregivers of those who received rehabilitation treatment. Caregivers were provided a 48-item survey and asked to choose their top ten information needs. Dementia caregivers' (n = 33) top needs were dealing with forgetfulness/confusion (91%) and repeating questions/actions (61%) in care recipients. Rehabilitation caregivers' (n = 40) top needs were handling care recipients' mobility problems (75%) and dealing with their own stress (65%). Dementia caregivers focused on care recipients' needs related to behavioral symptoms, whereas rehabilitation caregivers focused on needs related to physical care of care recipients and their own needs. PMID- 22087786 TI - Scope and mechanistic studies of electrophilic alkoxyetherification. AB - A one-pot electrophilic alkoxyetherification using an olefin, a cyclic ether, a carboxylic acid, and N-bromosuccinimide has been developed. The oxygen nucleophiles, the olefinic substrates, and the cyclic ether partners can be varied to produce a wide range of alkoxyether derivatives. PMID- 22087787 TI - Challenges to providing HIV prevention education to youth with disabilities in South Africa. AB - PURPOSE: In South Africa, little is known how HIV prevention education is implemented in schools for learners with disabilities. This article reports on findings from a study exploring the extent to which HIV education is reached to people with disabilities in South Africa, and the challenges faced by educators providing HIV prevention education to learners with disabilities. METHOD: A survey questionnaire completed by 34 schools for learners with special education needs in the Western Cape province of South Africa. Additional complimentary data were collected through interviews with a total of 21 members of staff at schools for learners with disabilities. RESULTS: Respondents recognise the importance of providing HIV prevention education for people with disabilities. Staff reports some challenges in providing HIV prevention education: barriers to communication; discomfort about issues of sexuality and disability; disagreements among staff about what is appropriate content for sexual health education; and fears of promoting sexual activity. CONCLUSIONS: There is a need for HIV prevention education to be specifically customized to the needs of the specific population. A general programme, which is included as part of a general curriculum and generally tailored to "mainstream" schools, would need to be adapted according to specific needs and disabling barriers faced. PMID- 22087788 TI - Controlled dynamics at an avoided crossing interpreted in terms of dynamically fluctuating potential energy curves. AB - The nonadiabatic nuclear wavepacket dynamics on the coupled two lowest (1)Sigma(+) states of the LiF molecule under the action of a control pulse is investigated. The control is achieved by a modulation of the characteristics of the potential energy curves using an infrared field with a cycle duration comparable to the time scale of nuclear dynamics. The transition of population between the states is interpreted on the basis of the coupled nuclear wavepacket dynamics on the effective potential curves, which are transformed from the adiabatic potential curves with use of a diabatic representation that diagonalizes the dipole-moment matrix of the relevant electronic states. The basic feature of the transition dynamics is characterized in terms of the notion of the collision between the dynamical crossing point and nuclear wavepackets running on such modulated potential curves, and the transition amplitude is mainly dominated by the off-diagonal matrix element of the time-independent electronic Hamiltonian in the present diabatic representation. The importance of the geometry dependence of the intrinsic dipole moments as well as of the diabatic coupling potential is illustrated both theoretically and numerically. PMID- 22087789 TI - Centrosomal and mitotic abnormalities in cell lines derived from papillary thyroid cancer harboring specific gene alterations. AB - BACKGROUND: Differentiated thyroid carcinoma offers a good model to investigate the possible correlation between specific gene mutations and chromosome instability. Papillary thyroid neoplasms are characterized by different mutually exclusive genetic alterations, some of which are associated with aneuploidy and aggressive phenotype. RESULTS: We investigated the centrosome status and mitotic abnormalities in three thyroid carcinoma-derived cell lines, each maintaining the specific, biologically relevant gene alteration harbored by the parental tumors: RET/PTC1 rearrangement in TPC1; heterozygous and homozygous BRAFV600E mutation in K1 and in B-CPAP, respectively. B-CPAP cells showed a statistically significant (P < 0.01) higher frequency of abnormal mitotic figures compared to TPC1 and K1 cells. CONCLUSIONS: Our data indicate that RET/PTC1 oncogenic activity is not related to mitotic chromosome impairment and missegregation whereas, based on the consistent difference in types/frequencies of centrosome and spindle abnormalities observed between K1 and B-CPAP cells, the hetero/homozygous allelic status of BRAFV600E mutation seems to be not irrelevant in respect to chromosomal instability development. PMID- 22087790 TI - Characteristics, practice patterns, and outcomes in patients with acute hypertension: European registry for Studying the Treatment of Acute hyperTension (Euro-STAT). AB - INTRODUCTION: Although effective strategies are available for the management of chronic hypertension, less is known about treating patients with acute, severe elevations in blood pressure. Using data from the European registry for Studying the Treatment of Acute hyperTension (Euro-STAT), we sought to evaluate 'real life' management practices and outcomes in patients who received intravenous antihypertensive therapy to treat an episode of acute hypertension. METHODS: Euro STAT is a European, hospital-based, observational study of consecutive adult patients treated with intravenous antihypertensive therapy while in the emergency department, perioperative unit or ICU. Enrolment took place between 1 July and 15 October 2009 in 11 hospitals in 7 European countries (Austria, Belgium, Germany, Italy, Spain, Sweden and the United Kingdom). RESULTS: The study population was composed of 791 consecutive patients (median age 69 years, 37% women). Median arterial blood pressure before treatment was 166 mmHg systolic blood pressure (IQR 141 to 190 mmHg) and 80 mmHg diastolic blood pressure (IQR 68 to 95). Nitroglycerine was the most commonly used antihypertensive treatment overall (40% of patients), followed by urapidil (21%), clonidine (16%) and furosemide (8%). Treatment was associated with hypotension in almost 10% of patients. Overall 30 day mortality was 4%, and new or worsening end-organ damage occurred in 19% of patients. CONCLUSIONS: High blood pressure requiring intravenous therapy is currently managed with a variety of agents in Europe, with those most commonly used being nitroglycerine, urapidil and clonidine. Patients with acute hypertension have substantial concomitant morbidity and mortality, and intravenous antihypertensive treatment is associated with hypotension in almost 10% of cases. PMID- 22087791 TI - Knowledge of obstetric danger signs and birth preparedness practices among women in rural Uganda. AB - BACKGROUND: Improving knowledge of obstetric danger signs and promoting birth preparedness practices are strategies aimed at enhancing utilization of skilled care in low-income countries. The aim of the study was to explore the association between knowledge of obstetric danger signs and birth preparedness among recently delivered women in south-western Uganda. METHODS: The study included 764 recently delivered women from 112 villages in Mbarara district. Community survey methods were used and 764 recently delivered women from 112 villages in Mbarara district were included in study. Interviewer administered questionnaire were used to collect data. Logistic regression analyses were conducted to explore the relationship between knowledge of key danger signs and birth preparedness. RESULTS: Fifty two percent of women knew at least one key danger sign during pregnancy, 72% during delivery and 72% during postpartum. Only 19% had knowledge of 3 or more key danger signs during the three periods. Of the four birth preparedness practices; 91% had saved money, 71% had bought birth materials, 61% identified a health professional and 61% identified means of transport. Overall 35% of the respondents were birth prepared. The relationship between knowledge of at least one key danger sign during pregnancy or during postpartum and birth preparedness showed statistical significance which persisted after adjusting for probable confounders (OR 1.8, 95% CI: 1.2-2.6) and (OR 1.9, 95% CI: 1.2-3.0) respectively. Young age and high levels of education had synergistic effect on the relationship between knowledge and birth preparedness. The associations between knowledge of at least one key danger sign during childbirth or knowledge that prolonged labour was a key danger sign and birth preparedness were not statistically significant. CONCLUSIONS: The prevalence of recently delivered women who had knowledge of key danger signs or those who were birth prepared was very low. Since the majority of women attend antenatal care sessions, the quality and methods of delivery of antenatal care education require review so as to improve its effectiveness. Universal primary and secondary education programmes ought to be promoted so as to enhance the impact of knowledge of key danger signs on birth preparedness practices. PMID- 22087792 TI - AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome. AB - BACKGROUND: To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance. RESULTS: Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA. CONCLUSIONS: AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts. PMID- 22087794 TI - Gastric neuroendocrine carcinoma after long-term use of proton pump inhibitor. AB - We present a case of a gastric neuroendocrine carcinoma in a patient with a history of long-term proton pump inhibitor (PPI) use. A 49-year-old man using PPI for the last 15 years due to gastroesophageal reflux disease developed progressive dysphagia, dyspepsia and weight loss. Upper gastrointestinal endoscopy, endoscopic ultrasonography and abdominal CT diagnosed a malignant tumor localized to a hiatal hernia. Fasting serum chromogranin A and gastrin concentrations were elevated (32 nmol/l and 159 pmol/l, respectively). Helicobacter pylori PCR analysis of antral biopsies was negative. Biopsies from endoscopically normal oxyntic mucosa showed enterochromaffin-like (ECL) cell hyperplasia. Tumor biopsies revealed a poorly differentiated neuroendocrine carcinoma. Sevier-Munger staining, immunohistochemistry and electron microscopy indicated ECL cell as origin of the tumor cells. Concerns have previously been raised about the safety of long-term PPI use due to a possible increased risk of cancer. This case illustrates a patient with a poorly differentiated neuroendocrine carcinoma with ECL cell characteristics probably induced by hypergastrinemia secondary to long-term PPI use. PMID- 22087795 TI - A randomised crossover placebo-controlled trial investigating the effect of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) on postchallenge plasma glucose and insulin levels in men and women. AB - This study examined the impact of brown seaweed on post-load plasma glucose and insulin concentrations in men and women. Twenty-three participants (11 men, 12 women) aged 19-59 years were recruited in this double-blind, randomized, placebo controlled crossover study. The test product consisted of a commercially available blend of brown seaweed (Ascophyllum nodosum and Fucus vesiculosus) with known inhibitory action on alpha-amylase and alpha-glucosidase activities (InSea2). Two 250 mg seaweed capsules and 2 placebo capsules were consumed on each occasion 30 min prior to the consumption of 50 g of carbohydrates from bread. Plasma glucose and insulin concentrations were measured over a period of 3 h postcarbohydrate ingestion at predetermined time points. Both treatments were separated by a 1-week washout period. Data were analysed using mixed models for repeated measures. Compared with placebo, consumption of seaweed was associated with a 12.1% reduction in the insulin incremental area under the curve (p = 0.04, adjusted for baseline) and a 7.9% increase in the Cederholm index of insulin sensitivity (p < 0.05). The single ingestion of 500 mg of brown seaweed had no significant effect on the glucose response (p = 0.24, adjusted for baseline). Glucose and insulin responses were similar between men and women. Consumption of the seaweed capsules was not associated with any adverse event. These data suggest that brown seaweed may alter the insulin homeostasis in response to carbohydrate ingestion. PMID- 22087796 TI - Malleability of human skeletal muscle sarcoplasmic reticulum to short-term training. AB - This study investigated the hypothesis that adaptations would occur in the sarcoplasmic reticulum in vastus lateralis soon after the onset of aerobic-based training consistent with reduced Ca2+-cycling potential. Tissue samples were extracted prior to (0 days) and following 3 and 6 days of cycling performed for 2 h at 60%-65% of peak aerobic power (VO2(peak)) in untrained males (VO2(peak) = 47 +/- 2.3 mL.kg-1.min-1; mean +/- SE, n = 6) and assessed for changes (nmol.mg protein-1.min-1) in maximal Ca2+-ATPase activity (V(max)), Ca2+-uptake, and Ca2+ release (phase 1 and phase 2) as well as the sarcoplasmic (endoplasmic) reticulum Ca2+-ATPase (SERCA) isoforms. Training resulted in reductions (p < 0.05) in SERCA1a at 6 days (-14%) but not at 3 days. For SERCA2a, reductions (p < 0.05) were also noted only at 6 days (-7%). For V(max), depressions (p < 0.05) were found at 6 days (172 +/- 11) but not at 3 days (176 +/- 13; p < 0.10) compared with 0 days (192 +/- 11). These changes were accompanied by a lower (p < 0.05) Ca2+-uptake at both 3 days (-39%) and 6 days (-48%). A similar pattern was found for phase 1 Ca2+-release with reductions (p < 0.05) of 37% observed at 6 days and 23% (p = 0.21) at 3 days of training, respectively. In a related study using the same training protocol and participant characteristics, microphotometric determinations of V(max) indicated reductions (p < 0.05) in type I at 3 days ( 27%) and at 6 days (-34%) and in type IIA fibres at 6 days (-17%). It is concluded that in response to aerobic-based training, sarcoplasmic reticulum Ca2+ cycling potential is reduced by adaptations that occur soon after training onset. PMID- 22087797 TI - Short-term muscle power and speed in preschoolers exhibit stronger tracking than physical activity. AB - The purpose of this study was to examine the tracking of short-term muscle power, speed, and physical activity over a 15-month period in a sample of healthy Canadian preschool-aged children. Seventeen preschoolers (age, 4.4 +/- 0.8 years) completed exercise testing and physical activity monitoring at baseline and follow-up separated by 14.6 +/- 4.1 months. Short-term muscle power was measured using a modified 10-s Wingate test with peak power and mean power normalized to body mass. Speed was assessed with a 25-m dash. Physical activity was measured by accelerometry (Actigraph GT1M) using a 3-s epoch over 7 consecutive days. Total physical activity and moderate-to-vigorous physical activity, expressed as a percentage of accelerometer wear time, were examined. Tracking of the variables between year 1 and year 2 was analyzed using Spearman rank order correlations and Kappa statistics. Paired t-tests were used to assess differences in performance and physical activity between year 1 and year 2. Total physical activity was not significantly different at year 2 (p > 0.05) and showed fair tracking (r = 0.51, p = 0.05; K = 0.30). Moderate-to-vigorous physical activity was increased at year 2 (p = 0.03) and exhibited poor tracking (r = 0.29, p = 0.28; K = 0.00). Short term muscle power and speed was increased at year 2 (p < 0.0001) and exhibited significant tracking: peak power (r = 0.72, p = 0.001; K = 0.46), mean power (r = 0.83, p = 0.00004; K = 0.82), and 25-m dash (r = 0.82, p = 0.0001; K = 0.47). Moderate-to-vigorous physical activity increased in this sample of boys and girls during the preschool years, and short-term muscle power and speed exhibited stronger tracking than physical activity. PMID- 22087798 TI - Distinct differentiation potential of "MSC" derived from cord blood and umbilical cord: are cord-derived cells true mesenchymal stromal cells? AB - Mesenchymal stromal cells (MSC) with distinct differentiation properties have been reported in many adult [eg, bone marrow (BM)] or fetal tissues [eg, cord blood (CB); umbilical cord (UC)] and are defined by their specific surface antigen expression and multipotent differentiation potential. The MSC identity of these cells should be validated by applying well-defined readout systems if a clinical application is considered. In order to determine whether cells isolated from human UC fulfill the criteria defined for MSC, the immunophenotype and differentiation potential including gene expression analysis of the most relevant lineage-specific markers were analyzed in the presented report in combination with the HOX-gene expression. Cells from the UC do not differentiate into osteoblasts demonstrated by Alizarin Red and Von Kossa staining in addition to real-time polymerase chain reaction (PCR)-analysis of runt-related transcription factor 2, bone sialoprotein, osteocalcin, osterix, bone morphogenetic proteins 2 and 4. Oil Red O staining as well as PCR analysis of peroxisome proliferator activated receptor-gamma, fatty acid-binding protein 4, and perilipin revealed an absent adipogenic differentiation. The lack of potential to differentiate into chondrocytes was documented by Alcian-Blue periodic acid-Schiff, Safranin O staining, and real-time PCR analysis of SOX9. Furthermore, neither endothelial nor myogenic differentiation was documented after induction of UC-MSC. In comparison to CB- and BM-derived cells, UC cells revealed an absent trilineage differentiation capacity in vitro. Therefore, these cells should not be termed "mesenchymal stromal cells". The UC cells can be distinguished from CB- and BM derived cells as well as from pericytes and foreskin fibroblasts by the expression of HOX-genes and the cell surface antigens CD56 and CD146. PMID- 22087799 TI - Functionalized STAT1 siRNA nanoparticles regress rheumatoid arthritis in a mouse model. AB - AIM: To develop and characterize an RGD peptide functionalized poly(lactide-co glycolytic) acid (PLGA) nanosystem to deliver a STAT1 siRNA to joint tissues in a mouse model of rheumatoid arthritis. METHODS: RGD-PLGA polymer was synthesized and used in preparing functionalized nanoparticles loaded with either tracking material or siRNA. The properties of the nanoparticles and stability of siRNA after encapsulation was assessed. Nanoparticle distribution was determined both noninvasively and based on analysis of dissected organs from arthritic and healthy mice. Arthritic mice were treated with weekly doses of STAT1 siRNA-loaded nanoparticles or controls. Clinical disease was assessed. Paws of arthritic mice were sectioned for histology or processed for RNA. STAT1, Mrc-1, and IL-10 mRNA abundance was determined by quantitative PCR. RESULTS: Nanoparticles protected the siRNA from serum degradation. The presence of RGD peptide on the nanoparticles increased paw tissue uptake in arthritic mice. Furthermore, RGD functionalization increased lung delivery of nanoparticles in arthritic mice but not in control mice. Disease regressed in the STAT1 siRNA-treated animals and progressed in all control groups. STAT1 mRNA levels were decreased in paws of treated animals, while Mrc-1 and IL-10 mRNA levels were increased. CONCLUSION: RGD functionalized PLGA nanoparticles encapsulating STAT1-targeted siRNAs are efficacious in the treatment of established arthritis, possibly through a selective inhibition of macrophage and dendritic cell activation. PMID- 22087800 TI - Synthesis, pharmacoscintigraphic evaluation and antitumor efficacy of methotrexate-loaded, folate-conjugated, stealth albumin nanoparticles. AB - The present study aims to develop a multifunctional nanoformulation based on technetium-99m labeled, folate conjugated, methotrexate-loaded human serum albumin nanoparticles (HSA NPs) and explore their potential in cancer theragnostics. MATERIALS & METHODS: Methotrexate-loaded HSA NPs were synthesized by a reverse microemulsion technique, followed by chemical crosslinking with glutaraldehyde. These NPs were conjugated with folic acid (FA) through a hydrophilic polyethylene glycol spacer to render them long-circulatory and augment their tumor-specific localization. The therapeutic conjugate was further radiolabeled with a gamma-emitter technetium-99m for real-time monitoring of its blood clearance kinetics and biodistribution through the measurement of blood/organ-associated radioactivity and scintigraphic imaging. RESULTS & CONCLUSION: In vitro cell-uptake and cytotoxicity studies corroborated that FA conjugation enabled these NPs to specifically target and kill folate-receptor overexpressing cancer cells via S phase arrest. Blood clearance kinetics and biodistribution studies clearly indicated that circulation time, as well as tumor specific localization of methotrexate-loaded HSA nanocarriers, could be significantly augmented upon polyethylene glycolylation and conjugation of FA. Finally, we demonstrated that these targeted HSA NPs inhibited tumor growth more effectively, as compared with the nontargeted controls. PMID- 22087801 TI - Expert Delphi survey on research and development into drugs for neglected diseases. AB - BACKGROUND: Tropical infectious diseases are called neglected, because they are, inter alia, characterized by an R&D deficit. A similar deficit exists for rare (orphan) diseases which neither promise a sufficient return on R&D investment. To encourage the development of treatments for rare diseases, orphan drug acts were created which contain financial and non-financial incentives for the pharmaceutical industry. Similar instruments aimed exclusively at neglected diseases do not yet exist. Proposals for a regulatory approach to promote R&D for neglected diseases include the application of selected orphan drug incentives, or the implementation of a Medical Research and Development Treaty (MRDT) with national funding obligations for medical R&D. We compiled and analyzed experts' opinions on causes for the treatment deficit for neglected diseases and on desirable and feasible measures to promote neglected disease R&D. Hereby, the focus was on mechanisms contained in orphan drug regulations and in the Medical Research and Development Treaty draft (Discussion draft 4, 2005). Lastly, we solicited experts' opinions on the desirability and feasibility of a regulatory instrument to foster R&D for neglected diseases. METHODS: An international online Delphi survey was conducted with 117 (first round) and 56 (second round) experts of different professional backgrounds and professional affiliations who formulated and ranked causes and solutions related to the treatment deficit for neglected diseases. RESULTS: In both rounds of survey, the majority of the participating experts (88.4% first round, 86.8% second round) advocated the development of a regulatory instrument to promote R&D for neglected diseases. Most experts (77.9% first round, 79.3% second round) also considered this to be a feasible option. With the exception of market exclusivity, which was viewed critically, key provisions contained in orphan drug regulations were judged favorably also for neglected diseases. A majority (87.1% first round, 77.2% second round) supported national funding obligations for neglected diseases which are proposed by the Medical Research and Development Treaty draft. CONCLUSIONS: While not all features of orphan drug regulations and of the MRDT draft received equal support, the view was expressed that a regulatory instrument would be a desirable and feasible measure to promote R&D for neglected diseases. PMID- 22087802 TI - Identification and characterization of genes differentially expressed in cherimoya (Annona cherimola Mill) after exposure to chilling injury conditions. AB - Cherimoyas (Annona cherimola), like other subtropical/tropical fruits, are susceptible to damage from exposure to temperatures between 0 and 5 degrees C (chilling injury, CI), which may affect fruit quality. To increase our understanding of the molecular mechanisms involved in the CI response, a forward suppression subtractive hybridization (SSH) cDNA library was constructed. In this work, we obtained 75 genes that could potentially be involved in the CI response. The CI induced activation of genes that are involved in a range of metabolic pathways, such as primary metabolism, transport, and endomembrane traffic, among others. We also characterized the expression of 12 selected genes in different A. cherimola tissues by polymerase chain reaction (PCR), and we confirmed the differential expression of a subset in CI fruits by real-time quantitative PCR (qPCR). The expression of six A. cherimola genes: annexin (AcAnex), UDP-glucose pyrophosphorylase (AcUGP), syntaxin of plants 71 (AcSyp71), 1-aminocyclopropane-1 carboxylic-acid synthase (AcACS), ubiquitin carrier-like protein (AcUCP), and enolase (AcEnol), was up-regulated after cold storage for 12 days at 0 degrees C. These results imply that selected genes could be related to the development of internal browning observed in cherimoyas after exposure to CI conditions. The information generated in this study provides new clues that may aid in understanding the cherimoya ripening process. PMID- 22087804 TI - Periodontal disease decreases insulin sensitivity and insulin signaling. AB - BACKGROUND: The purpose of this study is to investigate whether local inflammatory events, such as periodontal disease, are able to increase tumor necrosis factor-alpha (TNF-alpha) plasmatic concentration and decrease insulin sensitivity and insulin signaling in non-diabetic rats. METHODS: Forty-eight male Wistar rats (2 months old) were divided into two groups, with either ligature induced periodontal disease (LPD) or control conditions (CN). Experiments were performed in both groups 28 days after ligature placement. Plasmatic concentration of glycemia and TNF-alpha (n = 10) were analyzed by the glucose oxidase and enzyme-linked immunosorbent assay method, respectively. Insulin sensitivity (n = 7) was measured using the insulin tolerance test. Insulin signal transduction (n = 7) was measured by pp185 tyrosine phosphorylation status in insulin-sensitive tissues using the Western blotting method. RESULTS: The LPD group showed decreased insulin sensitivity (P <0.05), although no glycemic alterations were noted (P >0.05). TNF-alpha plasmatic concentration was higher in LPD rats compared to CN rats. In addition, a decrease in the pp185 tyrosine phosphorylation status was observed after insulin stimulus in both white adipose and skeletal muscle tissues of the LPD group compared with the CN group. CONCLUSIONS: LPD is able to cause alterations to both insulin signaling and insulin sensitivity, probably because of the elevation of TNF-alpha plasmatic concentration. Thus, the present results emphasize the importance of the prevention of local inflammatory diseases, such as periodontitis, to prevent diabetes mellitus. PMID- 22087803 TI - Double-masked randomized clinical trial evaluating the effect of a triclosan/copolymer dentifrice on periodontal healing after one-stage full-mouth debridement. AB - BACKGROUND: This study evaluates the effect of triclosan/copolymer dentifrice on the 6-month clinical response of patients with generalized severe chronic periodontitis (GSCP) treated with one-stage, full-mouth ultrasonic debridement (FMUD). METHODS: Thirty patients diagnosed with GSCP (>=8 teeth presenting probing depth [PD] >=5 mm and bleeding on probing [BOP]) were selected and randomly allocated to a control group (n = 15) subjected to FMUD and daily use of a placebo dentifrice or to a test group (n = 15) subjected to FMUD and daily use of a triclosan/copolymer dentifrice. Patients were analyzed for the following parameters: full-mouth plaque index (FMPI), full-mouth BOP score (FMBS), gingival recession, PD, and clinical attachment level (CAL). Patients were evaluated at 3 and 6 months by a calibrated and masked examiner. RESULTS: Initially, the groups presented similar periodontal conditions, with no significant differences in any of the parameters evaluated (P >0.05). In both groups, improvements in all periodontal parameters (P <0.05) were seen at the completion of the experimental period. Additionally, the test group showed lower FMPI (3 months) and FMBS (3 and 6 months) than the control group (P <0.05). Moreover, the CAL gain was significantly greater in the test group, especially at initially deep pockets (PD <=7 mm). Whereas in the control group the CAL gain in deep pockets was 2.7 +/- 0.6 mm, in the test group the CAL gain was 3.6 +/- 1.4 mm (P <0.05). CONCLUSION: Within the limits of the present study, the use of triclosan/copolymer dentifrice promoted additional clinical benefits in the treatment of GSCP treated by one stage FMUD. PMID- 22087805 TI - Clinical and microbiologic effects of commercially available dentifrice containing aloe vera: a randomized controlled clinical trial. AB - BACKGROUND: Certain plants used in folk medicine serve as a source of therapeutic agents that have antimicrobial and other multipotential effects. This prospective, randomized, placebo, and positively controlled clinical trial was designed to evaluate the clinical and microbiologic effects of a commercially available dentifrice containing aloe vera on the reduction of plaque and gingival inflammation in patients with gingivitis. METHODS: Ninety patients diagnosed with chronic generalized gingivitis were selected and randomly divided into three groups: group 1, placebo toothpaste; group 2, toothpaste containing aloe vera; and group 3, toothpaste with polymer and fluoride containing triclosan. Clinical evaluation was undertaken using a gingival index, plaque was assessed using a modification of the Quigley-Hein index, and microbiologic counts were assessed at baseline, 6 weeks, 12 weeks, and 24 weeks. A subjective evaluation was also undertaken by questionnaire. RESULTS: Toothpaste containing aloe vera showed significant improvement in gingival and plaque index scores as well as microbiologic counts compared with placebo dentifrice. These improvements were comparable to those achieved with toothpaste containing triclosan. CONCLUSION: Toothpaste containing aloe vera may be a useful herbal formulation for chemical plaque control agents and improvement in plaque and gingival status. PMID- 22087806 TI - A novel intraoral diabetes screening approach in periodontal patients: results of a pilot study. AB - BACKGROUND: This pilot study examines whether a novel diabetes screening approach using gingival crevicular blood (GCB) could be used to test for hemoglobin A1c (HbA1c) during periodontal visits. METHODS: Finger-stick blood (FSB) samples from 120 patients and GCB samples from those patients with adequate bleeding on probing (BOP) were collected on special blood collection cards and analyzed for HbA1c levels in a laboratory. The Pearson correlation coefficient was used to measure correlation between FSB and GCB HbA1c values for 75 paired FSB and GCB samples. A receiver-operator characteristic curve (ROC) analysis was performed to determine an optimal GCB HbA1c criterion value for a positive diabetes screen. RESULTS: For the 75 paired samples, the Pearson correlation coefficient was 0.842. The ROC analysis identified a criterion value of 6.3% for the GCB HbA1c test with high sensitivity (0.933) and high specificity (0.900), corresponding to FSB HbA1c values >=6.5% (in the diabetes range). Using this GCB HbA1c criterion value for 27 additional paired samples, in which there was an unidentified component observed to coelute within the elution window of GCB HbA1c in the laboratory, there was agreement between FSB and GCB values for 24 of the pairs according to whether both were within or outside of the diabetes range. CONCLUSION: Using a criterion value of 6.3%, GCB samples are acceptable for HbA1c testing to screen for diabetes in most persons with BOP at the GCB collection site. PMID- 22087807 TI - Lipopolysaccharide and hypoxia-induced HIF-1 activation in human gingival fibroblasts. AB - BACKGROUND: We previously reported that chronic periodontal inflammation causes the accumulation of the transcriptional activator hypoxia-inducible factor-1alpha (HIF-1alpha) in human gingival fibroblasts (HGFs) in vivo. Here, evidence is provided that bacterial lipopolysaccharides (LPS) and cellular hypoxia, both associated with periodontitis, can individually, or in combination, lead to the accumulation and activation of HIF-1 in HGF in vitro. METHODS: Primary gingival fibroblasts were cultured from human gingival biopsies. HIF-1alpha peptide from HGFs treated with Escherichia coli LPS under normoxia or hypoxia was detected by nuclear protein extraction, immunoprecipitation, immunoblotting, and immunocytofluorescence. HIF-1alpha transcripts were detected using reverse transcription polymerase chain reaction (PCR). The transcript expression levels of vascular endothelial growth factor-A (VEGF-A), a downstream gene of HIF 1alpha, were assessed by quantitative real-time PCR. RESULTS: Two HIF-1alpha splicing transcription variants were found to be constitutively expressed in HGFs. E. coli LPS induced a dose- and time-dependent nuclear accumulation of HIF 1alpha peptide in HGFs. This accumulation could be attenuated by treatment with a Toll-like receptor 4 (TLR4)-neutralizing antibody. Under hypoxia, LPS further increased HIF-1alpha accumulation in HGFs. VEGF-A transcript expression was upregulated by LPS under both normoxia and hypoxia but was downregulated by pretreatment with TLR4-neutralizing antibody or the specific HIF-1alpha inhibitor 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole. CONCLUSION: LPS induces the nuclear accumulation of HIF-1alpha in HGFs and induces HIF-1 biologic activity under normoxia or hypoxia possibly through TLR4. PMID- 22087808 TI - Catalytic proficiency: the extreme case of S-O cleaving sulfatases. AB - As benchmarks for judging the catalytic power of sulfate monoesterases, we sought to determine the rates of spontaneous hydrolysis of unactivated alkyl sulfate monoesters by S-O bond cleavage. Neopentyl sulfate proved to be unsuitable for this purpose, since it was found to undergo hydrolysis by a C-O bond cleaving mechanism with rearrangement of its carbon skeleton. Instead, we examined the temperature dependence of the spontaneous hydrolyses of aryl sulfate monoesters, which proceed by S-O cleavage. Extrapolation of a Bronsted plot [log(k(25)(N)) = (-1.81 +/- 0.09) pK(a)(LG) + (3.6 +/- 0.7)] based on the rate constants at 25 degrees C for hydrolysis of a series of sulfate monoesters to a pK(a)(LG) value of 16.1, typical of an aliphatic alcohol, yields k(25)(N) = 3 * 10(-26) s(-1). Comparison of that value with established k(cat) values of bacterial sulfatases indicates that these enzymes produce rate enhancements (k(cat)/k(uncat)) of up to 2 * 10(26)-fold for the hydrolysis of sulfate monoesters. These rate enhancements surpass by several orders of magnitude the ~10(21)-fold rate enhancements that are generated by phosphohydrolases, the most powerful biological catalysts previously known. The hydrolytic rates of phosphate and sulfate monoesters are compared directly, and the misleading impression that the two classes of ester are of similar reactivity is dispelled. PMID- 22087814 TI - Correlation between coronary artery disease severity, left ventricular mass index and carotid intima media thickness, assessed by radio-frequency. AB - BACKGROUND: Intima-media thickness of the common carotid artery (CCA-IMT) is a validated marker of systemic atherosclerosis process. The aim of this study was to evaluate the association between coronary artery disease (CAD), left ventricular hypertrophy (LVH) and CCA-IMT, assessed by Radio Frequency-Quality Intima Media Thickness (RFQIMT) method, the next generation of IMT real-time measurement, based on the direct analysis of the radiofrequency signal and endowed with high accuracy and reproducibility in early detection of arterial wall thickness. METHODS: 115 patients (76 men, mean age: 65.1 +/- 12 years) referred to our department and shown significant (>= 70% luminal obstruction) stenosis at least in one major epicardial coronary artery were studied. Coronary angiograms were divided for severity and extent of the disease: 79 patients (69%) had one, 24 patients (21%) two, 12 patients (10%) three major epicardial coronary arteries with >= 70% stenosis. All patients underwent echocardiography and carotid ultrasound examination, assessed by RF. RESULTS: Dividing RFQIMT data in tertiles, dyslipidaemia (31 patients with IMT >= 1.20 mm vs 16 with IMT = 0.91 1.19 vs 25 with IMT <= 0.9, p = 0.004), LVMI (153.5 +/- 20.6 g/m2 in IMT >= 1.20 mm vs 131.2 +/- 8.4 g/m2 in IMT = 0.91-1.19 mm vs 114.3 +/- 11.1 g/m2 in IMT <= 0.9 mm, P < 0.001) and number of high stenosed coronary arteries (IMT >= 1.20 mm population more often showed three vessel diseases than IMT <= 0.90 mm one, P < 0.001) seemed to be significantly related to CCA-IMT increases. Furthermore, LVMI is positively related to IMT (r = 0.91; P < 0.001). In a multivariate regression model (R2 = 0.88), RFQIMT remained significantly associated with the dyslipidemia (regression coefficient +/- standard error [SE]: 0.057 +/- 0.023; p = 0.017), LVMI (regression coefficient +/- SE: 0.01 +/- 0.001; P < 0.0001) and number of damaged coronaries (regression coefficient +/- SE: 0.0174 +/- 0.028; P < 0.0001). CONCLUSIONS: RFQIMT is a sophisticated method for carotid ultrasound evaluation. Its evaluation in patients with at least one important major epicardial coronary vessel stenosis would help the accuracy in the general assessment of the number of coronary lesions in these patients. PMID- 22087815 TI - beta-1,3-D-glucan schizophyllan/poly(dA) triple-helical complex in dilute solution. AB - A certain length of poly(deoxyadenylic acid) (dA(X)) can form a novel complex with beta-1,3-D-glucan schizophyllan (SPG) with a stoichiometric composition of one dA binding two main chain glucoses. We measured dilute solution properties for the complex with light and small-angle X-ray scattering as well as intrinsic viscosity and found that the complex behaves as a semiflexible rod without branching or cross-linking. We analyzed the data with the wormlike cylinder model, and the chain dimensions and the persistence length for the complexes were consistently determined. The chain flexibility was reduced to almost 25% upon complexation for dA/SPG and to 15% for S-dA/SPG, where S-dA denotes the phosphorothioated DNA analogue. The changes in the molar mass per unit length and the diameter indicated that the helix was elongated or stretched along the axis direction upon the complexation. PMID- 22087816 TI - The N-aryl aminocarbonyl ortho-substituent effect in Cu-catalyzed aryl amination and its application in the synthesis of 5-substituted 11-oxo-dibenzodiazepines. AB - Double amination of ortho-substituted aryl bromides proceeded under mild conditions to afford 5-substituted 11-oxo-dibenzodiazepines, which revealed that there is a strong ortho-substituent effect caused by N-aryl aminocarbonyl groups during copper-catalyzed aryl amination. PMID- 22087817 TI - Factors that influence low back pain in people with a stoma. AB - PURPOSE: People with a stoma believe that there is a link between their surgery and low back pain (LBP). AIM: To explore factors relating to (i) core stability in people with a stoma and LBP and (ii) biopsychosocial factors related to LBP. METHODS: Adults with an ileostomy and LBP (n = 17) completed (i) a range of standardised instruments, (ii) clinical tests and (iii) an ultrasound scan of right and left transversus abdominis (TrA). RESULTS: The findings showed moderate pain and disability: RMDQ: median = 12 (IQR: 9.5-13), EQ-5D health state: mean = 6.9 (+/-1.75), BPI pain severity: median = 4.5 (IQR: 2.87-5.4). The TrA contraction was less on the operated than the unoperated side and this was linked to less control for BKFO to the operated side, and the presence of a parastomal hernia. Co-morbidities were associated with greater balance problems during the stork test (p < 0.05). Men had more fear avoidance (p < 0.05) on the FABQ regarding physical activity. DISCUSSION: Abdominal function may be altered after stoma surgery leading to reduced ability to perform functional tasks and a possible increased risk of back pain. These results should be viewed with caution due to the small sample size. PMID- 22087818 TI - Effects of BCR-ABL inhibitors on anti-tumor immunity. AB - In chronic myeloid leukemia (CML), BCR-ABL-mediated oncogenic signaling can be successfully targeted with the BCRABL- inhibitors imatinib, nilotinib, and dasatinib leading to complete cytogenetic (Philadelphia chromosome not detectable upon cytogenetic testing of bone marrow) and even complete molecular (BCR-ABL not detectable by PCR in peripheral blood) responses. However, CML apparently can not be cured by BCR-ABL inhibitors alone, likely due to treatment-resistance of CML stem/progenitor cells, which provokes a relapse of disease after cessation of therapy. Evidence from patients treated with allogenic stem cell transplantation or IFN-alpha points to an important role of anti-tumor immunity for durable control of CML disease. Data from multiple in vitro and ex vivo studies indicate that BCR-ABL inhibitors may also influence anti-tumor immunity. Varying effects on different immune effector cell subsets and of the different compounds have been reported, the latter being due to their particular and diverse potency and spectrum of target kinases. As multiple approaches presently aim to combine BCR ABL inhibition with immunotherapeutic strategies to improve disease control in CML, immunomodulatory effects of the available BCR-ABL inhibitors may be of direct clinical relevance. Here we review the available data regarding the effects of imatinib, nilotinib, and dasatinib on dendritic cells, T cells and natural killer cells as important cellular components of anti-tumor immunity. PMID- 22087819 TI - Proteasome inhibitors and modulators of angiogenesis in multiple myeloma. AB - Survival of patients affected by Multiple Myeloma (MM), a B-cell tumor of malignant plasma cells, has dramatically improved, owing to the recent introduction of the proteasome inhibitor (PI) Bortezomib and of the immunomodulatory drugs (IMiDs). This major advance originates from accumulating knowledge on MM biology, leading to the development of drugs targeting not only MM cells, but also their microenvironment. Indeed, the disease develops as a result of genetic abnormalities and of reciprocal interactions between MM cells and the permissive BM microenvironment, which delivers growth- and pro-survival signals and confers resistance to drugs. As for solid tumors, bone marrow (BM) angiogenesis is emerging as a critical component of MM development and progression, and hence as an attractive therapeutic target for the disease. The patho-physiology of MM associated angiogenesis is complex and involves a plethora of soluble factors, cellular players and mechanisms. Moreover, the hypoxic microenvironment inside the BM might significantly contribute to the induction and maintenance of a pro-angiogenic profile, given the well-known role of hypoxia in promoting angiogenesis in all its forms. Here we present an overview of the literature focusing on the mechanisms implicated in the "angiogenic switch", which corresponds to the transition from the avascular to the vascular phase of the disease. We also review evidence on the anti-angiogenic effects of PI and IMiDs, which substantially contribute to their anti-MM activity. Finally, we summarize possible caveats and perspectives about antiangiogenic strategies that could be addressed to improve the efficacy of treatments for MM patients. PMID- 22087820 TI - Modulating mesenchymal stromal cell function with cholesterol synthesis inhibitors. AB - There is increasing evidence that statins, inhibitors of 3-hydroxyl-3 methylglutaryl coenzyme A reductase, can effectively be used not only in the treatment of hypercholesterolemia, but also in other human disorders; indeed, statins have strong anti-inflammatory and immunomodulatory effects, so that they can influence the onset and outcome of inflammation and autoimmunity. On the other hand, it has been shown that statins can affect growth and survival of solid tumour and leukemic cells, thus they have been proposed in the treatment of neoplasias as multiple myeloma, in association with drugs, as thalidomide, known to act on the cancer microenvironment. In the current view, tumor microenvironment include many cell types that interact with tumor cells: among them, stromal and endothelial cells, macrophages and dendritic cells, the various types of lymphocytes such as NK cells, B and T cells. The interplay between all these cell populations, and the balance between these, determines whether there is a tumour cell growth promotion or inhibition. In haematological malignancies, such as multiple myeloma, chronic lymphocytic and myeloid leukemias and follicular lymphomas, the survival, drug-resistance and proliferation of leukemic cells have been shown to be largely dependent on a supportive microenvironment, so that some cellular components of it, mainly mesenchymal stromal cells, cancer associated fibroblasts and macrophages, are now proposed as targets of new therapies. Herein, we analyze the effects that statins can exert on cancer cells, stromal cells and human natural killer cells, to discuss whether they can be proposed as anti-cancer drugs. PMID- 22087821 TI - Aminobisphosphonates and Toll-like receptor ligands: recruiting Vgamma9Vdelta2 T cells for the treatment of hematologic malignancy. AB - Gamma delta (gammadelta) T cells are intrinsically important for preventing the development and progression of hematologic cancers. These innate T cells are particularly suited for the application of cancer therapy due to the fact they: 1) recognize transformed cells independent of antigen processing or presentation by classical MHC molecules, and 2) embody the anti-tumour effector functions of both NK cells and cytotoxic T cells. It was serendipitously discovered that aminobisphosphonates (ABP), a class of drugs used as adjuvant cancer therapy for the treatment of malignant osteolytic bone disease, have the unexpected side effect of potently activating the antitumour effector functions of human peripheral gammadelta T cells. Such beneficial therapeutic synergisms are rare, and no time has been wasted to determine how to best harness the anti-cancer potential of gammadelta T cells and ABP. Despite promising experimental results, the full clinical potential of this immunotherapeutic strategy has been hampered by the subversive strategies employed by cancer cells to obstruct activation of anti-tumour immune responses. These include the promotion of regulatory T cells (Tregs) that maintain tumour tolerance and the corruption of dendritic cell (DC) function and maturation. Toll-like receptor (TLR) agonists have a long history of breaking free of tumour-induced immune-suppression by resetting DC function and abrogating Treg induced tolerance. This review presents data to support the notion that TLR signalling may perfectly complement the anti-tumour synergy of ABP and activated gammadelta T cells, and this combined innate artillery could provide the necessary ammunition to topple malignancy's stronghold on the immune system. PMID- 22087823 TI - Biomolecules produced by mangrove-associated microbes. AB - This review summarizes the sources and characteristics of various natural products that can be extracted from mangrove-associated microbes with a focus on bioactivity, highlighting the unique chemical diversity of these metabolic products. PMID- 22087822 TI - The role of the adenosinergic pathway in immunosuppression mediated by human regulatory T cells (Treg). AB - Tumor-induced dysfunction of immune cells is a common problem in cancer. Tumors induce immune suppression by many different mechanisms, including accumulation of regulatory T cells (Treg). Adaptive Treg (Tr1) generated in the tumor microenvironment express CD39 and CD73 ectonucleotidases, produce adenosine and are COX2+PGE2+. Adenosine and PGE2 produced by Tr1 or tumor cells bind to their respective receptors on the surface of T effector cells (Teff) and cooperate in up-regulating cytosolic 3'5'-cAMP levels utilizing adenylyl cyclase isoform 7 (AC 7). In Teff, increased cAMP mediates suppression of anti-tumor functions. Treg, in contrast to Teff, seem to require high cAMP levels for mediating suppression. This differential requirement of Treg and Teff for cAMP offers an opportunity for pharmacologic interventions using selected inhibitors of the adenosine/PGE2 pathways. Blocking of adenosine/PGE2 production by Tr1 or blocking binding of these factors to their receptors on T cells or inhibition of cAMP synthesis in Teff all represent novel therapeutic strategies that used in combination with conventional therapies could restore anti-tumor functions of Teff . At the same time, these inhibitors could disarm Tr1 cells by depriving them of the factors promoting their generation and activity or by down-regulating 3'5'-cAMP levels. Thus, the pharmacologic control of Treg-Teff interactions offers a novel strategy for restoration of anti-tumor Teff functions and silencing of Treg. Used in conjunction with anti-cancer drugs or with immune therapies, this strategy has a potential to improve therapeutic effects by preventing or reversing tumor-induced immune suppression. PMID- 22087824 TI - Determinants of increased cardiovascular disease in obesity and metabolic syndrome. AB - Obesity is associated with an increased mortality and morbidity for cardiovascular disease (CVD) and adipose tissue is recognised as an important player in obesity-mediated CVD. The diagnosis of the metabolic syndrome (MS) appears to identify substantial additional cardiovascular risk above and beyond the individual risk factors, even though the pathophysiology underlying this evidence is still unravelled. The inflammatory response related to fat accumulation may influence cardiovascular risk through its involvement not only in body weight homeostasis, but also in coagulation, fibrinolysis, endothelial dysfunction, insulin resistance (IR) and atherosclerosis. Moreover, there is evidence that oxidative stress may be a mechanistic link between several components of MS and CVD, through its role in inflammation and its ability to disrupt insulin-signaling. The cross-talk between impaired insulin-signaling and inflammatory pathways enhances both metabolic IR and endothelial dysfunction, which synergize to predispose to CVD. Persistent platelet hyperreactivity/activation emerges as the final pathway driven by intertwined interactions among IR, adipokine release, inflammation, dyslipidemia and oxidative stress and provides a pathophysiological explanation for the excess risk of atherothrombosis in this setting. Despite the availability of multiple interventions to counteract these metabolic changes, including appropriate diet, regular exercise, antiobesity drugs and bariatric surgery, relative failure to control the incidence of MS and its complications reflects both the multifactorial nature of these diseases as well as the scarce compliance of patients to established strategies. Evaluation of the impact of these therapeutic strategies on the pathobiology of atherothrombosis, as discussed in this review, will translate into an optimized approach for cardiovascular prevention. PMID- 22087825 TI - Serotonin and its receptors in the human CNS with new findings - a mini review. AB - Serotonin (5-hydroxytryptamine, 5-HT) is well known to be closely associated with emotional disorders, such as depression and schizophrenia. The seven main members of 5-HT receptor family including the different subtypes are involved in the functional pathways in the brain and their balance in activity helps to maintain the normal mental stability. As any detrimental changes in the 5-HT system is believed to alter emotion in human, different drugs including serotonin reuptake inhibitors (SSRIs) are nowadays commonly used as anti- depressives. In this review, 5-HT(1A) and 5-HT(2A) receptors and serotonergic positive cells in the human were highlighted in particular. It is hoped that this review will give a map of these major 5-HT receptors and serotonergic neurons in the human CNS to facilitate further deciphering of their functions. PMID- 22087826 TI - Flavonoids as acetylcholinesterase inhibitors. AB - Flavonoids are new promising potential natural compounds for treating Alzheimer's disease (AD). Actually most promising drugs for symptomatic treatment of AD are acetylcholinesterase inhibitors (AChEI). Flavonoids with AChE inhibitory activity and due to their well known antioxidant activity could be new multipotent drugs for AD treatment. This work focuses on natural and synthetic flavonoids inhibitors of the enzyme acetylcholinesterase (AChE). Over, all this review refers to 128 flavonoids, which are classified in chemical structure, and summarizes 64 references. PMID- 22087827 TI - Nanostructures for drug delivery to the brain. AB - This review aims to summarize present approaches employed in delivering drugs to the central nervous system. Changes in blood-brain barrier (BBB) function have been reported in several neurological disorders. A brief description of the blood brain barrier and the main pathologies related to this barrier disfunction are described. Treatments for these disorders are based on several available strategies for delivering drugs into the brain, through circumvention of the BBB, as disruption of the BBB, prodrugs, molecular Trojan horses, among others. Particular attention will be placed on nanocarriers and more specifically on polymeric nanoparticles, which are presented as the most promising strategy for CNS delivery, helping drugs to be targeted more efficiently to the brain. This also allows attacking previously untreatable disorders such as brain tumors and other neurodegenerative diseases. New strategies and technologies commercialized by different pharmaceutical companies are also included. PMID- 22087828 TI - Immunossupressant and organ transplantation: immunophilins targeting agent and alternative therapies. AB - Since the first attempt to replace a dysfunctional organ, clinics and scientific had to overcome many setbacks in order to warrant the success and viability of both the organ and the receptor. Despite the improvement of surgical procedures, some grafts fail within the following days or week due to immunologic rejection. Many ongoing researches are still seeking the perfect immunossupresors. Calcineurin targeting agents have been consolidated as a worldwide immnunossupressant therapy, but due to its widely functional role in many cell types, this strategy often represents a highly risk therapy due to side effects observed with these agents. Here we summarized the latest and past knowledge regarding immunossupression therapies, including the promising and widely used Immunophilin-targeting antagonist therapies. PMID- 22087829 TI - Insights into immunophilin structure and function. AB - The immunophilins are proteins which are capable of influencing the immune response in combination with an immunosuppressive drug. Their natural function, however, is mainly the cis/trans isomerization of peptidyl-prolyl bonds in other proteins. This review lists all immunophilin structure coordinates currently available in the RCSB protein data bank and highlights the key active-site factors that define their catalytic and immunological action. In addition, an overview of biologically-relevant functions is provided for various immunophilin members. PMID- 22087830 TI - The chemical biology of immunophilin ligands. AB - The immunophilin ligands cyclosporin A, FK506 and rapamycin are best known for their immunosuppressive properties and their clinical use in transplantation medicine. These compounds or their analogs are also clinically used or investigated in various types of cancer, coronary angioplasty, dermatology, hepatitis C infections, and neuroprotection. Furthermore, the role of immunophilins in various pathologies is increasingly being recognized, supporting the preclinical drug development for novel immunophilin targets. Finally, immunophilin ligands are widely used as sophisticated tools in chemical biology. This review shows the progress on three major areas made in the last five years. An update of the immunosuppressive ligands and their clinical applications is discussed in the first part of the review, followed by a discussion about the emerging immunophilin targets and their respective ligands. The final section gives a detailed assessment of immunophilin ligand-based tools. PMID- 22087831 TI - Role of FK506 binding proteins in neurodegenerative disorders. AB - Protein misfolding has been implicated in the pathophysiology of several neurodegenerative 'amyloidoses' that includes Alzheimer's, Parkinson's, Huntington's disease, frontotemporal dementia and amyotrophic lateral sclerosis. Accumulation of misfolded proteins into ordered fibrillar intra- or extracellular amyloids results in brain lesions that in turn lead to injury and neuronal loss. The appearance of protein aggregates in the diseased brain hints at an inability of cellular chaperones to properly assist folding of client proteins. Not surprisingly, studies involving cell-based and animal models of the neurodegenerative diseases have shown that overexpression of molecular chaperones can provide neuroprotection. Together with identification of new targets for symptomatic relief of motor and non-motor defects in neurodegenerative disorders, there is a critical unmet clinical need for the development of novel neuroprotective molecules. One such promising class of compounds are neuroimmunophilin ligands (NILs). Derived from FK506 (tacrolimus), NILs have been shown to be efficacious in a number of neurodegenerative disorders. The ability of these nonimmunosuppressive NILs to protect neurons is modulated, in part, by a large family of co-chaperone proteins called the FK506 binding proteins (FKBPs). This review focuses on the roles of FKBPs in neurodegenerative disorders with an emphasis on the cellular mechanisms responsible for their neuroprotective and neurotrophic activities. We discuss the structural features of FKBPs and the mode of action of NILs. For brevity, we limit our discussion to those FKBPs that are particularly enriched in the nervous system. We hope that such information will aid in the rational design of new and improved NILs for ameliorating neurodegenerative disorders. PMID- 22087832 TI - Immunophilin dysfunction and neuropathology. AB - In case of nervous damages, like nervous system trauma or various neurodegenerative diseases such as dementia or Parkinson, several treatments are available to restore neurological function. In spite of these treatments, results are often insufficient or not satisfactory in many neurologic diseases, especially for central nervous system (CNS) lesions. To minimize neurological dysfunction, it is critical to reduce neuronal death, avoiding loss of the synaptic connections, and securing viable neurons to extend axons. Unfortunately, there are no effective strategies to fulfill these basic needs except for some cases of peripheral neural damage up to now. Rescue of damaged neurons, stimulation of neurogenesis and transplantation of nervous tissue are strategies proposed to prevent neurodegenerative disorders. A number of studies have recently reported successful axon regeneration and neurological recovery by using immunosuppressants, such as FK506. Immunosuppressants act as excellent agents for enhancing the rate and extent of axon regeneration and neurological recovery. FK506 and other neuroimmunophilin ligands (NILs) might reverse neuronal degeneration. In several animal models mimicking Parkinson's disease, dementia and surgical damage, NILs induces resprouting, by acting as neurotrophic agents and preventing nerve damage, although more studies are necessary to identify new NILs with neuroprotective action, but lacking the side immunological effects observed in the ligands analyzed to date. This review explores the new clinical role of immunosuppressants in the treatment of nerve surgery of autologous, allografts or xenografts. Results of studies regarding immunosuppressant treatment of nervous system trauma and neurodegenerative diseases, like neurogenic erectile dysfunction, will be here considered. PMID- 22087833 TI - Immunophilins and cardiovascular complications. AB - Immunophilins belong to a highly conserved family of proteins with cis-trans peptidyl-prolyl isomerase activity, generally classified by their ability to selectively bind specific immunosuppressive drugs, thereby regulating their activity. Immunophilins include Cyclophilins (CyPs), which are specific targets of the immunosuppressant drug cyclosporin A (CsA); FKBPs (FK506-binding proteins), that are sensitive to both FK506 (tacrolimus) and rapamycin (sirolimus); and FCBPs which are sensitive to CsA and FK506. Immunophilins are expressed in multiple human tissues, including brain, heart, kidney, liver and lung and regulate functions as diverse as intracellular calcium signaling, protein transport, protein folding and gene transcription. In particular, immunophilins play key functional roles in the cardiovascular system, where they can associate with proteins such as ryanodine and IP3 receptors (RyR and IP3R), calcineurin, and mitochondrial permeability transition pore (MPTP) and Heat-shock proteins-caveolin-cholesterol complex and regulate their function. The biological importance of immunophilins is further revealed by the pathophysiology, as they have been implicated in several cardiovascular diseases, including vascular stenosis, atherosclerosis, heart failure and arrhythmias. This review summarizes some of the most recent studies on immunophilins and focuses on their roles in the mechanisms underlying the cardiovascular disease. PMID- 22087834 TI - Immunophilins and thrombotic disorders. AB - The immunophilin family includes a large group of proteins with peptidyl prolyl isomerase activity (PPI-ase). Immunophilins chaperone activity has been documented to be crucial for the correct folding and activation of many proteins. Thus, they have been subjected of intense investigation since they were firstly described in the last decades of the past century. Many of these studies have been focused on leukocyte constitutively expressed immunophilins, due to their relevance in the correct folding, and subsequently, sensitization and activation of the glycoprotein receptor (RGBs) of lymphocyte T CD4+ and Treg, hence regulating immunological responses against pathogen insults. Several clinical trials have been completed in the last decade reporting that administration of immunophilin-binding drugs, derived from macrolide lactones, like cyclosporine A (CsA) and tacrolimus (FK506), induced successful results in preventing organ rejection. By contrast, the expression of immunophilins and their physiological function remain poorly investigated in others cell types, such as platelets, where a reduced number of studies presenting evidences of immunophilins expression and their physiological contribution have been published, despite a number of clinical trials have noticed side effects of these drugs in thrombosis and platelet count, thus suggesting a possible regulatory function of immunophilins in human platelets, which is reviewed here. PMID- 22087836 TI - Interacting with gamma-secretase for treating Alzheimer's disease: from inhibition to modulation. AB - Drugs currently used for the treatment of Alzheimer's disease (AD) produce limited clinical benefits, and there is no disease-modifying therapy yet available. Compounds that inhibit or modulate gamma-secretase, the pivotal enzyme that generates beta-amyloid (Abeta), are potential therapeutics for AD. This article briefly reviews the profile of gamma-secretase inhibitors and modulators that have reached the clinic. Studies in both transgenic and non-transgenic animal models of AD have indicated that gamma-secretase inhibitors, administered by the oral route, are able to lower brain Abeta concentrations. However, scanty data are available on the effects of these compounds on brain Abeta deposition after prolonged administration. gamma-Secretase inhibitors may cause abnormalities in the gastrointestinal tract, thymus, spleen, skin, and decrease in lymphocytes and alterations in hair color in experimental animals and in man, effects believed to be associated with the inhibition of the cleavage of Notch, a transmembrane receptor involved in regulating cell-fate decisions. Unfortunately, two large Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of a detrimental cognitive and functional effect of the drug. These detrimental effects were mainly ascribed to the inhibition of the processing of an unknown substrate of gamma-secretase. It has been also hypothesized that the detrimental cognitive effects observed after semagacestat administration are due to the accumulation of the neurotoxic precursor of Abeta (the carboxy-terminal fragment of amyloid precursor protein, APP, or CTFbeta) resulting from the block of the gamma secretase cleavage activity on APP. Some non-steroidal anti-inflammatory drugs and other small organic molecules have been found to modulate gamma-secretase shifting its cleavage activity from longer to shorter Abeta species without affecting Notch cleavage. However, two large Phase III studies in mild AD patients with tarenflurbil, a putative gamma-secretase modulator, were also completely negative. The failure of tarenflurbil was ascribed to low potency and brain penetration. New more selective gamma-secretase inhibitors and more potent, more brain penetrant gamma-secretase modulators are being developed with the hope of overcoming the previous setbacks. Further understanding of the reasons of the failures of these gamma-secretase-based drugs in AD may be important for the future research on effective treatments for this devastating disease. PMID- 22087837 TI - Re-wiring the circuit: mitochondria as a pharmacological target in liver disease. AB - Mitochondria play a key role in intracellular energy-generating processes, cell life and death, and are heavily involved in several metabolic pathways by integrating signaling networks; thus, a very large number of conditions are characterized by mitochondrial bioenergetic in humans. Often, mitochondrial changes are directly or indirectly dependent on the activation of intracellular stress cascades or death receptor-mediated pathways. Reactive oxygen species (ROS) formation, glutathione (GSH) depletion, protein alkylation and respiratory complex alterations are major events associated with mitochondrial dysfunction and represent critical initiating events in most forms of chronic liver disease. Through creating an analogy with a disrupted electric circuit gone bad, the present review focuses initially on how hepatic mitochondrial bioenergetics is affected in the context of drug and disease-induced liver failure and how targeting mitochondria with several antioxidant agents can be helpful for preventing the disruption of the mitochondrial electric circuit. PMID- 22087835 TI - The emerging role of large immunophilin FK506 binding protein 51 in cancer. AB - FK506 binding protein 51 (FKBP51) is an immunophilin physiologically expressed in lymphocytes. Very recently, aberrant expression of this protein was found in melanoma; FKBP51 expression correlates with melanoma aggressiveness and is maximal in metastatic lesions. FKBP51 promotes NF-kappaB activation and is involved in the resistance to genotoxic agents, including anthracyclines and ionizing radiation. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates several biological processes through protein-protein interaction. There is increasing evidence that FKBP51 hyperexpression is associated with cancer and this protein has a relevant role in sustaining cell growth, malignancy, and resistance to therapy. There is also evidence that FKBP ligands are potent anticancer agents, in addition to their immunosuppressant activity. In particular, rapamycin and its analogs have shown antitumor activity across a variety of human cancers in clinical trials. Although, classically, rapamycin actions are ascribed to inhibition of mTOR, recent studies indicate FKBP51 is also an important molecular determinant of the drug's anticancer activity. The aim of this article is to review the functions of FKBP51, especially in view of the recent findings that this protein is a potential oncogene when deregulated and a candidate target for signaling therapies against cancer. PMID- 22087838 TI - The 2009 influenza pandemic: promising lessons for antiviral therapy for future outbreaks. AB - The influenza A virus is the main circulating influenza virus in the human population. It can cause disease also in birds and other mammals and is responsible for annual epidemics and occasional pandemics. The most known and deadly pandemic was the "Spanish flu" (influenza type A/H1N1), which struck the human population between 1918 and 1919, with probably the heaviest toll ever recorded in terms of human lives. The most recent flu pandemic, caused in 2009 by the swine-origin reassortant virus (pH1N1), has raised several critical issues in terms of our preparedness in responding fast to new pandemic influenza strains. Probably, the most instructive lesson that has been learned from the 2009 pandemic, was that the speed of manufacturing and distributing an effective vaccine will not be able to keep up with the pace of a rapidly spreading pandemic virus, failing to grant accessibility to the vaccine for a significant percentage of the susceptible population, before the onset of the pandemic peak. Thus, our first and most effective line of defense against a pandemic influenza virus, particularly in the early phases, are the antiviral drugs. Here we analyze our current understanding of the influenza pandemic viruses, in general, and of the pH1N1 in particular, along with the most recent approaches being pursued to design new anti-influenza drugs. PMID- 22087840 TI - Waterpipe smoking among health sciences university students in Iran: perceptions, practices and patterns of use. AB - BACKGROUND: In recent years waterpipe smoking has become a popular practice amongst young adults in eastern Mediterranean countries, including Iran. The aim of this study was to assess waterpipe smoking perceptions and practices among first-year health sciences university students in Iran and to identify factors associated with the initiation and maintenance of waterpipe use in this population. RESULTS: Out of 371 first-year health sciences students surveyed, 358 eight students completed a self-administered questionnaire in the classrooms describing their use and perceptions towards waterpipe smoking. Two hundred and ninety six responders met study inclusion criteria. Waterpipe smoking was common among first-year health sciences university students, with 51% of students indicating they were current waterpipe smokers. Women were smoking waterpipes almost as frequently as men (48% versus 52%, respectively). The majority of waterpipe smokers (75.5%) indicated that the fun and social aspect of waterpipe use was the main motivating factor for them to continue smoking. Of waterpipe smokers, 55.3% were occasional smokers, using waterpipes once a month or less, while 44.7% were frequent smokers, using waterpipes more than once a month. A large number of frequent waterpipe smokers perceived that waterpipe smoking was a healthier way to use tobacco (40.6%) while only 20.6% thought it was addictive. Compared to occasional smokers, significantly more frequent smokers reported waterpipe smoking was relaxing (62.5% vs. 26.2%, p = 0.002), energizing (48.5% vs. 11.4%, p = 0.001), a part of their culture (58.8% vs. 34.1%, p = 0.04), and the healthiest way to use tobacco (40.6% vs. 11.1%, p = 0.005). CONCLUSIONS: Social and recreational use of waterpipes is widespread among first-year health sciences university students in Iran. Women and men were almost equally likely to be current waterpipe users. Public health initiatives to combat the increasing use of waterpipes among university students in Iran must consider the equal gender distribution and its perception by many waterpipe smokers as being a healthier and non-addictive way to use tobacco. PMID- 22087839 TI - Extracellular signal-regulated kinases modulate DNA damage response - a contributing factor to using MEK inhibitors in cancer therapy. AB - The Raf-MEK-ERK pathway is commonly activated in human cancers, largely attributable to the extracellular signal-regulated kinases (ERKs) being a common downstream target of growth factor receptors, Ras, and Raf. Elevation of these up stream signals occurs frequently in a variety of malignancies and ERK kinases play critical roles in promoting cell proliferation. Therefore, inhibition of MEK mediated ERK activation is very appealing in cancer therapy. Consequently, numerous MEK inhibitors have been developed over the years. However, clinical trials have yet to produce overwhelming support for using MEK inhibitors in cancer therapy. Although complex reasons may have contributed to this outcome, an alternative possibility is that the MEK-ERK pathway may not solely provide proliferation signals to malignancies, the central scientific rationale in developing MEK inhibitors for cancer therapy. Recent developments may support this alternative possibility. Accumulating evidence now demonstrated that the MEK ERK pathway contributes to the proper execution of cellular DNA damage response (DDR), a major pathway of tumor suppression. During DDR, the MEK-ERK pathway is commonly activated, which facilitates the proper activation of DDR checkpoints to prevent cell division. Inhibition of MEK-mediated ERK activation, therefore, compromises checkpoint activation. As a result, cells may continue to proliferate in the presence of DNA lesions, leading to the accumulation of mutations and thereby promoting tumorigenesis. Alternatively, reduction in checkpoint activation may prevent efficient repair of DNA damages, which may cause apoptosis or cell catastrophe, thereby enhancing chemotherapy's efficacy. This review summarizes our current understanding of the participation of the ERK kinases in DDR. PMID- 22087841 TI - Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study. AB - INTRODUCTION: It is debated whether early trauma-induced coagulopathy (TIC) in severely injured patients reflects disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype, acute coagulopathy of trauma shock (ACoTS) or yet other entities. This study investigated the prevalence of overt DIC and ACoTS in trauma patients and characterized these conditions based on their biomarker profiles. METHODS: An observational study was carried out at a single Level I Trauma Center. Eighty adult trauma patients (>=18 years) who met criteria for full trauma team activation and had an arterial cannula inserted were included. Blood was sampled a median of 68 minutes (IQR 48 to 88) post-injury. Data on demography, biochemistry, injury severity score (ISS) and mortality were recorded. Plasma/serum was analyzed for biomarkers reflecting tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments, Annexin V, thrombomodulin, syndecan-1), coagulation activation/inhibition (prothrombinfragment 1+2, thrombin/antithrombin-complexes, antithrombin, protein C, activated protein C, endothelial protein C receptor, protein S, tissue factor pathway inhibitor, vWF), factor consumption (fibrinogen, FXIII), fibrinolysis (D dimer, tissue-type plasminogen activator, plasminogen activator inhibitor-1) and inflammation (interleukin (IL)-6, terminal complement complex (sC5b-9)). Comparison of patients stratified according to the presence or absence of overt DIC (International Society of Thrombosis and Hemostasis (ISTH) criteria) or ACoTS (activated partial thromboplastin time (APTT) and/or international normalized ratio (INR) above normal reference). RESULTS: No patients had overt DIC whereas 15% had ACoTS. ACoTS patients had higher ISS, transfusion requirements and mortality (all P < 0.01) and a biomarker profile suggestive of enhanced tissue, endothelial cell and glycocalyx damage and consumption coagulopathy with low protein C, antithrombin, fibrinogen and FXIII levels, hyperfibrinolysis and inflammation (all P < 0.05). Importantly, in non-ACoTS patients, apart from APTT/INR, higher ISS correlated with biomarkers of enhanced tissue, endothelial cell and glycocalyx damage, protein C activation, coagulation factor consumption, hyperfibrinolysis and inflammation, that is, resembling that observed in patients with ACoTS. CONCLUSIONS: ACoTS and non-ACoTS may represent a continuum of coagulopathy reflecting a progressive early evolutionarily adapted hemostatic response to the trauma hit and both are parts of TIC whereas DIC does not appear to be part of this early response. PMID- 22087842 TI - Effects of a robot-assisted training of grasp and pronation/supination in chronic stroke: a pilot study. AB - BACKGROUND: Rehabilitation of hand function is challenging, and only few studies have investigated robot-assisted rehabilitation focusing on distal joints of the upper limb. This paper investigates the feasibility of using the HapticKnob, a table-top end-effector device, for robot-assisted rehabilitation of grasping and forearm pronation/supination, two important functions for activities of daily living involving the hand, and which are often impaired in chronic stroke patients. It evaluates the effectiveness of this device for improving hand function and the transfer of improvement to arm function. METHODS: A single group of fifteen chronic stroke patients with impaired arm and hand functions (Fugl Meyer motor assessment scale (FM) 10-45/66) participated in a 6-week 3-hours/week rehabilitation program with the HapticKnob. Outcome measures consisted primarily of the FM and Motricity Index (MI) and their respective subsections related to distal and proximal arm function, and were assessed at the beginning, end of treatment and in a 6-weeks follow-up. RESULTS: Thirteen subjects successfully completed robot-assisted therapy, with significantly improved hand and arm motor functions, demonstrated by an average 3.00 points increase on the FM and 4.55 on the MI at the completion of the therapy (4.85 FM and 6.84 MI six weeks post therapy). Improvements were observed both in distal and proximal components of the clinical scales at the completion of the study (2.00 FM wrist/hand, 2.55 FM shoulder/elbow, 2.23 MI hand and 4.23 MI shoulder/elbow). In addition, improvements in hand function were observed, as measured by the Motor Assessment Scale, grip force, and a decrease in arm muscle spasticity. These results were confirmed by motion data collected by the robot. CONCLUSIONS: The results of this study show the feasibility of this robot-assisted therapy with patients presenting a large range of impairment levels. A significant homogeneous improvement in both hand and arm function was observed, which was maintained 6 weeks after end of the therapy. PMID- 22087844 TI - Deposition of aerosol particles in a model vitreous chamber. AB - The purpose of this study was to assess quantitatively the aerosol deposition in a model eye chamber to identify the mechanism(s) of deposition and delivery efficiency for application in retinal disease treated with vitrectomy. Dry aerosol particles were produced with mixtures of fluorescein and a variable concentration of cesium chloride, which ranged in aerodynamic size from 0.6 to 1.3 um. The aerosol was injected through a small inlet tube into Teflon chambers that had a vented, spherical cavity (diameter 3/4"). Two filling times of 60 s and 90 s were used. Although significant loss occurred in the syringe, the mass deposited within the chambers increased with aerosol concentration and ranged from 0.5 to nearly 15 ug. Between 60 and 90% of the mass was deposited on the lower surface of the chamber. The mechanism of deposition was consistent with diffusion through a boundary layer during filling followed by sedimentation of the remaining suspended aerosol particles. Based on these results, an aerosol with a median particle size of 1.3 um was shown to provide a therapeutically effective dose of 5-fluorouracil. The approach is general and can be applied to the aerosol delivery of other drugs to the vitreous chamber. PMID- 22087843 TI - Cell type-dependent gene regulation by Staufen2 in conjunction with Upf1. AB - dendritic mRNA transport machines. Although Stau2 is thought to be involved in the dendritic targeting of several mRNAs in neurons, the mechanism whereby Stau2 regulates these mRNAs is unknown. To elucidate the functions of Stau2, we screened for novel binding partners by affinity purification of GST-tagged Stau2 from 293F cells. RESULTS: Three RNA helicases, RNA helicase A, Upf1 and Mov10, were identified in Stau2-containing complexes. We focused our studies on Upf1, a key player in nonsense-mediated mRNA decay. Stau2 was found to bind directly to Upf1 in an RNA-independent manner in vitro. Tethering Stau2 to the 3' untranslated region (UTR) of a reporter gene had little effect on its expression in HeLa cells. In contrast, when the same tethering assay was performed in 293F cells, we observed an increase in reporter protein levels. This upregulation of protein expression by Stau2 turned out to be dependent on Upf1. Moreover, we found that in 293F cells, Stau2 upregulates the reporter mRNA level in an Upf1 independent manner. CONCLUSIONS: These results indicate that the recruitment of Stau2 alone or in combination with Upf1 differentially affects the fate of mRNAs. Moreover, the results suggest that Stau2-mediated fate determination could be executed in a cell type-specific manner. PMID- 22087845 TI - Investigation of ABCB1 1236 and 2677 SNPs in patients with peptic ulcer. AB - OBJECTIVE: P-gp, encoded by ABCB1 gene, is an ATP-binding membrane pump, which exports substrates from the cell including drugs and xenobiotics. Changes in the function of P-gp as a result of polymorphism could have an impact in some diseases' risks and treatment outcomes. The aim of the study was to determine the significance of the ABCB1 gene SNPs: 1236 and 2677 for peptic ulcer risk and development of Helicobacter pylori infection in peptic ulcer patients. MATERIAL AND METHODS: One hundred and ninety-five biopsy specimens obtained from peptic ulcer patients (investigated group) were genotyped using sequencing for common SNPs of ABCB1: 1236 and 2677. Genotyping data were compared with the results from healthy subjects (control) and with the presence of H. pylori infection, which was estimated by urease test. RESULTS: No statistically significant difference in frequency of genotypes and alleles for the SNPs were found between the investigated group and the control. However, in the peptic ulcer patients, mutant TT homozygotes and those who carried at least one allele T for the polymorphisms 1236 and 2677 were observed more frequently than the control group. In the peptic ulcer group, there were no significant dependences between the presence of H. pylori infection and the investigated polymorphisms other than more frequent occurrence of TT 1236 homozygous in the group of infected women (p = 0.0298). CONCLUSIONS: The TT genotype and the mutated allele T for the polymorphisms 1236 and 2677 could increase peptic ulcer risk. ABCB1 1236 polymorphism may also be associated with an increased likelihood of H. pylori infection development, especially in women. PMID- 22087846 TI - Exercise metabolism during moderate-intensity exercise in children with cystic fibrosis following heavy-intensity exercise. AB - Muscle metabolism is increased following exercise in healthy individuals, affecting exercise metabolism during subsequent physical work. We hypothesized that following heavy-intensity exercise (HIE), disease factors in children with cystic fibrosis (CF) would further exacerbate exercise metabolism and perceived exertion during subsequent exercise. Nineteen children with CF (age, 13.4 +/- 3.1 years; 10 female) and 19 healthy controls (age, 13.8 +/- 3.5 years; 10 female) performed 10 bouts of HIE interspersed with 1 min of recovery between each bout. Three minutes later participants completed a 10-min moderate-intensity exercise (MIE) test (test 1). The MIE test was subsequently repeated 1 h (test 2) and 24 h (test 3) later. Each MIE test was identical and participants exercised at individualized work rates, calibrated by an initial graded maximal cardiopulmonary exercise test, while metabolic and perceived exertion measurements were taken. Following HIE, mixed-model ANOVAs showed a significant difference in oxygen uptake (VO2) and rating of perceived exertion (RPE) between the 2 groups across the MIE tests (p < 0.01). In controls, VO2 (L.min-1) and RPE decreased significantly from test 1 to test 2 (p < 0.01) and test 2 to test 3 (p < 0.05). However, in children with CF, VO2 (L.min-1) increased significantly from test 1 to test 2 (p < 0.01), while RPE did not differ, both VO2 and RPE decreased significantly from test 2 to test 3 (p < 0.01). In conclusion, following HIE the metabolic and perceptual responses to MIE in both groups decreased 24 h later during test 3. These data show that children with mild-to-moderate CF have the capability to perform HIE and 24 h allows sufficient time for recovery. PMID- 22087848 TI - Psychomotor deficits associated with hyponatremia: a retrospective analysis. AB - Hyponatremia (serum sodium concentration [Na+] < 136 mEq/L) is a potentially life threatening condition. Recent evidence (Renneboog, Musch, Vandemergel, Manto, & Decaux, 2006) shows that even mild hyponatremia is associated with disorders of balance/gait. This retrospective analysis explored the influence of serum [Na+] on neuropsychological (NP) measurements at baseline from 44 patients with chronic hyponatremia who participated in an efficacy and safety study of an experimental compound over a decade ago. Group mean serum [Na+] was 124.8 +/- 4.9 mEq/L. Age adjusted partial correlations were computed between serum [Na+] and NP measurements, 39% of which were statistically significant--all involving psychomotor functioning. These findings replicate and extend previous observations that psychomotor deficits are, at least in part, associated with hyponatremia in these patients. While chronic hyponatremia is known to have deleterious effects on quality of life, motor and gait disturbances represent manifestations of mild hyponatremia that have until now gone unrecognized. A new class of medication, vasopressin antagonists, has been shown to correct hyponatremia. It will be important to explore the effects of correcting hyponatremia on psychomotor functioning in individuals with hyponatremia. PMID- 22087847 TI - beta-PIX is critical for transplanted mesenchymal stromal cell migration. AB - Bone marrow-derived mesenchymal stromal cells (MSCs) have been used successfully as a source of stem cells for treating neurodegenerative diseases. However, for reasons that are not clear, autologous MSC transplants have not yielded successful results in human trials. To test one possible reason, we compared the migratory ability of MSCs from amyotrophic lateral sclerosis (ALS) patients with those of healthy controls. We found that MSCs derived from ALS patients (ALS MSCs) had a reduced ability to migrate, which may explain why autologous transplantation is not successful. We also found that expression of one of the intracellular factors implicated in migration, beta-PIX, was significantly reduced in ALS-MSCs compared with healthy stem cells. Restoration of beta-PIX expression by genetic manipulation restored the migratory ability of ALS-MSCs, and inhibition of beta-PIX expression with shRNA reduced the migration of healthy MSCs. We suggest that transplantation of allogeneic or genetically modified autologous stem cells might be a more promising strategy for ALS patients than transplantation of autologous stem cells. PMID- 22087849 TI - Integrated microdevice for long-term automated perfusion culture without shear stress and real-time electrochemical monitoring of cells. AB - Electrochemical techniques based on ultramicroelectrodes (UMEs) play a significant role in real-time monitoring of chemical messengers' release from single cells. Conversely, precise monitoring of cells in vitro strongly depends on the adequate construction of cellular physiological microenvironment. In this paper, we developed a multilayer microdevice which integrated high aspect ratio poly(dimethylsiloxane) (PDMS) microfluidic device for long-term automated perfusion culture of cells without shear stress and an independently addressable microelectrodes array (IAMEA) for electrochemical monitoring of the cultured cells in real time. Novel design using high aspect ratio between circular "moat" and ring-shaped micropillar array surrounding cell culture chamber combined with automated "circular-centre" and "bottom-up" perfusion model successfully provided continuous fresh medium and a stable and uniform microenvironment for cells. Two weeks automated culture of human umbilical endothelial cell line (ECV304) and neuronal differentiation of rat pheochromocytoma (PC12) cells have been realized using this device. Furthermore, the quantal release of dopamine from individual PC12 cells during their culture or propagation process was amperometrically monitored in real time. The multifunctional microdevice developed in this paper integrated cellular microenvironment construction and real-time monitoring of cells during their physiological process, and would possibly provide a versatile platform for cell-based biomedical analysis. PMID- 22087850 TI - Implementation of patient education at first and second dispensing of statins in Dutch community pharmacies: the sequel of a cluster randomized trial. AB - BACKGROUND: As a result of the previous part of this trial, many patients with cardiovascular disease were expected to receive a statin for the first time. In order to provide these patients with comprehensive information on statins, as recommended by professional guidance, education at first and second dispensing of statins had to be implemented. This study was designed to assess the effectiveness of an intensive implementation program targeted at pharmacy project assistants on the frequency of providing education at first dispensing (EAFD) and education at second dispensing (EASD) of statins in community pharmacies. METHODS: The participating community pharmacies were clustered on the basis of local collaboration, were numbered by a research assistant and subsequently an independent statistician performed a block randomization, in which the cluster size (number of pharmacies in each cluster) was balanced. The pharmacies in the control group received a written manual on the implementation of EAFD and EASD; the pharmacies in the intervention group received intensive support for the implementation. The impact of the intensive implementation program on the implementation process and on the primary outcomes was examined in a random coefficient logistic regression model, which took into account that patients were grouped within pharmacy clusters. RESULTS: Of the 37 pharmacies in the intervention group, 17 pharmacies (50%) provided EAFD and 12 pharmacies (35.3%) provided EASD compared to 14 pharmacies (45.2%, P = 0.715) and 12 pharmacies (38.7%, P = 0.899), respectively, of the 34 pharmacies in the control group. In the intervention group a total of 72 of 469 new statin users (15.4%) received education and 49 of 393 patients with a second statin prescription (12.5%) compared to 78 of 402 new users (19.4%, P = 0.944) and 35 of 342 patients with a second prescription (10.2%, P = 0.579) in the control group. CONCLUSION: The intensive implementation program did not increase the frequency of providing EAFD and EASD of statins in community pharmacies. TRIAL REGISTRATION: clinicaltrials.gov NCT00509717. PMID- 22087851 TI - Effects of auxins on sorgoleone accumulation and genes for sorgoleone biosynthesis in sorghum roots. AB - Sorgoleone is a major component of the hydrophobic root exudate of Sorghum bicolor and is of particular interest to plant chemical ecology as well as agriculture. Sorgoleone was evaluated in this study to observe the expression levels of genes involved in its biosynthesis in response to auxins. Sorgoleone content varied widely according to the duration of application and the concentrations of the auxins. When the application time was increased, the sorgoleone content increased accordingly for all concentrations of IBA (1, 3, and 5 mg/L) and at 1 mg/L for both IAA and NAA. In this study, five different sorgoleone biosynthetic genes were observed, namely DES2, DES3, ARS1, ARS2, and OMT3, which are upregulated in response to IAA, IBA, and NAA. Transcript accumulation was apparent for all genes, but particularly for DES2, which increased up to 475-fold and 180-fold following 72 h exposure to NAA and IBA, respectively, compared to no treatment. PMID- 22087856 TI - Photocatalytic reduction of carbon dioxide over Ag cocatalyst-loaded ALa4Ti4O15 (A = Ca, Sr, and Ba) using water as a reducing reagent. AB - Ag cocatalyst-loaded ALa(4)Ti(4)O(15) (A = Ca, Sr, and Ba) photocatalysts with 3.79-3.85 eV of band gaps and layered perovskite structures showed activities for CO(2) reduction to form CO and HCOOH by bubbling CO(2) gas into the aqueous suspension of the photocatalyst powder without any sacrificial reagents. Ag cocatalyst-loaded BaLa(4)Ti(4)O(15) was the most active photocatalyst. A liquid phase chemical reduction method was better than impregnation and in situ photodeposition methods for the loading of the Ag cocatalyst. The Ag cocatalyst prepared by the liquid-phase chemical reduction method was loaded as fine particles with the size smaller than 10 nm on the edge of the BaLa(4)Ti(4)O(15) photocatalyst powder with a plate shape during the CO(2) reduction. CO was the main reduction product rather than H(2) even in an aqueous medium on the optimized Ag/BaLa(4)Ti(4)O(15) photocatalyst. Evolution of O(2) in a stoichiometric ratio (H(2)+CO:O(2) = 2:1 in a molar ratio) indicated that water was consumed as a reducing reagent (an electron donor) for the CO(2) reduction. Thus, an uphill reaction of CO(2) reduction accompanied with water oxidation was achieved using the Ag/BaLa(4)Ti(4)O(15) photocatalyst. PMID- 22087857 TI - The influence of topical prostaglandin analogues in inflammation after selective laser trabeculoplasty treatment. AB - PURPOSE: Reducing intraocular pressure (IOP) seems to be the only treatment that slows progression in glaucoma. The IOP can be decreased by pharmaceutical treatment, laser [selective laser trabeculoplasty (SLT)] treatment, or surgery. Prostaglandin analogues have been postulated to share action mechanisms with SLT and to possibly diminish the effects of SLT treatment. The aim of the current study was to investigate the effects of prostaglandin analogues in inflammation and IOP reduction after SLT treatment. METHODS: Prospective nonrandomized study. One hundred and eighteen patients were included in the study. INCLUSION CRITERIA: Glaucoma (open-angle or pseudoexfoliation glaucoma) patients who will be treated with SLT. Inflammation was measured with a laser flare meter (Kowa FM-500). Measurements were made before SLT and then 2 h, 1 week, and 1 month after SLT treatment. IOP was also checked at the same time intervals. The SLT treatment was performed over 90 degrees . All patients were divided into two groups: those receiving prostaglandins analogues and those treated with nonprostaglandin analogues. RESULTS: Inflammation before and after SLT showed no significant difference between the groups at all the time intervals studied (t-test, before: P=0.16; 2 h: P=0.14; 1 week: P=0.12; and 1 month: P=0.36). IOP reduction showed no significant difference between the groups (t-test, P=0.31). CONCLUSIONS: SLT treatment effects do not seem to be influenced by the use of prostaglandin analogues. PMID- 22087858 TI - Upregulation of low-density lipoprotein receptor after exposure to transforming growth factor-beta2 in tenon's capsule fibroblasts from patients with glaucoma. AB - PURPOSE: The aim of this study was to investigate the dynamic alteration of a low density lipoprotein receptor (LDLr) and its binding and uptake of LDL after exposure to transforming growth factor-beta(2) (TGF-beta(2)) in Tenon's capsule fibroblasts from glaucoma patients. METHODS: Tenon's capsule fibroblasts obtained from patients who had undergone selective glaucoma surgery were cultured and stimulated with different concentrations (0.1-10 ng/mL) of TGF-beta(2) for 1, 3, 5, and 7 days. Expression of LDLr mRNA was detected with relative quantification real-time reverse transcription-polymerase chain reaction, and expression of the corresponding protein was demonstrated with western blot. The extent of binding and uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI)-labeled LDL by GTFs was also checked. RESULTS: After exposure to TGF beta(2), LDLr was upregulated at the mRNA and protein levels in a concentration dependent and/or time-dependent manner with a peak at a concentration of 5 ng/mL TGF-beta(2). Binding and uptake of LDL were time dependent, reaching saturation at the first 6 h. CONCLUSIONS: This study shows that LDLr has a dose- and/or time effect relationship with TGF-beta(2) in Tenon's capsule fibroblasts from glaucoma patients. The results suggest that LDLr may play an important role in wound healing and scar formation in the activated Tenon's capsule fibroblasts from patients with glaucoma. PMID- 22087859 TI - Effect of the Cannabinoid Receptor-1 antagonist SR141716A on human adipocyte inflammatory profile and differentiation. AB - BACKGROUND: Obesity is characterized by inflammation, caused by increase in proinflammatory cytokines, a key factor for the development of insulin resistance. SR141716A, a cannabinoid receptor 1 (CB1) antagonist, shows significant improvement in clinical status of obese/diabetic patients. Therefore, we studied the effect of SR141716A on human adipocyte inflammatory profile and differentiation. METHODS: Adipocytes were obtained from liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. Media and cells were collected for secretory (ELISA) and expression analysis (qPCR). Triglyceride accumulation was observed using oil red-O staining. Cholesterol was assayed by a fluorometric method. 2-AG and anandamide were quantified using isotope dilution LC-MS. TLR-binding experiments have been conducted in HEK-Blue cells. RESULTS: In LPS-treated mature adipocytes, SR141716A was able to decrease the expression and secretion of TNF-a. This molecule has the same effect in LPS-induced IL-6 secretion, while IL-6 expression is not changed. Concerning MCP-1, the basal level is down-regulated by SR141716A, but not the LPS-induced level. This effect is not caused by a binding of the molecule to TLR4 (LPS receptor). Moreover, SR141716A restored adiponectin secretion to normal levels after LPS treatment. Lastly, no effect of SR141716A was detected on human pre-adipocyte differentiation, although the compound enhanced adiponectin gene expression, but not secretion, in differentiated pre-adipocytes. CONCLUSION: We show for the first time that some clinical effects of SR141716A are probably directly related to its anti-inflammatory effect on mature adipocytes. This fact reinforces that adipose tissue is an important target in the development of tools to treat the metabolic syndrome. PMID- 22087860 TI - Comparison of lichen, conifer needles, passive air sampling devices, and snowpack as passive sampling media to measure semi-volatile organic compounds in remote atmospheres. AB - A wide range of semivolatile organic compounds (SOCs), including pesticides and polycyclic aromatic hydrocarbons (PAHs), were measured in lichen, conifer needles, snowpack and XAD-based passive air sampling devices (PASDs) collected from 19 different U.S. national parks in order to compare the magnitude and mechanism of SOC accumulation in the different passive sampling media. Lichen accumulated the highest SOC concentrations, in part because of its long (and unknown) exposure period, whereas PASDs accumulated the lowest concentrations. However, only the PASD SOC concentrations can be used to calculate an average atmospheric gas-phase SOC concentration because the sampling rates are known and the media is uniform. Only the lichen and snowpack SOC accumulation profiles were statistically significantly correlated (r = 0.552, p-value <0.0001) because they both accumulate SOCs present in the atmospheric particle-phase. This suggests that needles and PASDs represent a different composition of the atmosphere than lichen and snowpack and that the interpretation of atmospheric SOC composition is dependent on the type of passive sampling media used. All four passive sampling media preferentially accumulated SOCs with relatively low air-water partition coefficients, while snowpack accumulated SOCs with higher log K(OA) values compared to the other media. Lichen accumulated more SOCs with log K(OA) > 10 relative to needles and showed a greater accumulation of particle-phase PAHs. PMID- 22087861 TI - Ultrasound-responsive thrombus treatment with zinc-stabilized gelatin nano complexes of tissue-type plasminogen activator. AB - This study is undertaken to design zinc-stabilized gelatin nano-complexes of tissue-type plasminogen activator (t-PA) for thrombolytic therapy where the t-PA activity can be recovered in the blood circulation upon ultrasound irradiation. Various molecular weights of gelatin were complexed with t-PA by their simply mixing in aqueous solution. Then, zinc acetate, calcium acetate or magnesium acetate was added to form nano-sized gelatin-t-PA complexes. The complexes had the apparent molecular size of about 100 nm. When zinc ions were added to the gelatin-t-PA complexes, the t-PA activity was suppressed most strongly to 57% of the original, free t-PA activity. Upon ultrasound exposure in vitro, the t-PA activity was fully recovered. A cell culture experiment with L929 fibroblasts demonstrated no cytotoxicity of complexes at the concentration used for the in vivo experiment. The half-life of t-PA in the blood circulation prolonged by the complexation with gelatin and zinc ions. The zinc-stabilized t-PA-gelatin complex is a promising t-PA delivery system which can manipulate the thrombolytic activity by the local ultrasound irradiation. PMID- 22087863 TI - Maximum a posteriori Bayesian estimation of mycophenolic Acid area under the concentration-time curve: is this clinically useful for dosage prediction yet? AB - This review seeks to summarize the available data about Bayesian estimation of area under the plasma concentration-time curve (AUC) and dosage prediction for mycophenolic acid (MPA) and evaluate whether sufficient evidence is available for routine use of Bayesian dosage prediction in clinical practice. A literature search identified 14 studies that assessed the predictive performance of maximum a posteriori Bayesian estimation of MPA AUC and one report that retrospectively evaluated how closely dosage recommendations based on Bayesian forecasting achieved targeted MPA exposure. Studies to date have mostly been undertaken in renal transplant recipients, with limited investigation in patients treated with MPA for autoimmune disease or haematopoietic stem cell transplantation. All of these studies have involved use of the mycophenolate mofetil (MMF) formulation of MPA, rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation. Bias associated with estimation of MPA AUC using Bayesian forecasting was generally less than 10%. However some difficulties with imprecision was evident, with values ranging from 4% to 34% (based on estimation involving two or more concentration measurements). Evaluation of whether MPA dosing decisions based on Bayesian forecasting (by the free website service https://pharmaco.chu limoges.fr) achieved target drug exposure has only been undertaken once. When MMF dosage recommendations were applied by clinicians, a higher proportion (72-80%) of subsequent estimated MPA AUC values were within the 30-60 mg . h/L target range, compared with when dosage recommendations were not followed (only 39-57% within target range). Such findings provide evidence that Bayesian dosage prediction is clinically useful for achieving target MPA AUC. This study, however, was retrospective and focussed only on adult renal transplant recipients. Furthermore, in this study, Bayesian-generated AUC estimations and dosage predictions were not compared with a later full measured AUC but rather with a further AUC estimate based on a second Bayesian analysis. This study also provided some evidence that a useful monitoring schedule for MPA AUC following adult renal transplant would be every 2 weeks during the first month post transplant, every 1-3 months between months 1 and 12, and each year thereafter. It will be interesting to see further validations in different patient groups using the free website service. In summary, the predictive performance of Bayesian estimation of MPA, comparing estimated with measured AUC values, has been reported in several studies. However, the next step of predicting dosages based on these Bayesian-estimated AUCs, and prospectively determining how closely these predicted dosages give drug exposure matching targeted AUCs, remains largely unaddressed. Further prospective studies are required, particularly in non-renal transplant patients and with the EC-MPS formulation. Other important questions remain to be answered, such as: do Bayesian forecasting methods devised to date use the best population pharmacokinetic models or most accurate algorithms; are the methods simple to use for routine clinical practice; do the algorithms actually improve dosage estimations beyond empirical recommendations in all groups that receive MPA therapy; and, importantly, do the dosage predictions, when followed, improve patient health outcomes? PMID- 22087864 TI - Kinetic nomograms assist individualization of drug regimens. AB - BACKGROUND AND OBJECTIVES: Therapeutic drug monitoring is applied to a range of drugs. To predict an appropriate dosing regimen, models based on Bayesian techniques have been used. However, this approach requires a well trained professional and sophisticated software. The objectives of this study were first to develop kinetic nomograms as a useful tool to achieve individual drug blood concentrations within the therapeutic window, using few samples and in a short period of time; and second to evaluate the performance of these nomograms in dosage adjustment and compare them with the Bayesian procedure by use of simulation. METHODS: Kinetic nomograms involve collection of concentration-time profiles following repeated administrations of a fixed identification protocol and targeting of a steady-state concentration. The profiles divide the concentration-time space into several areas, each of them corresponding to a given adjusted drug dose. Kinetic nomograms are grounded on the statistical description of the interindividual variability provided by population pharmacokinetic approaches. To use them, the assayed drug concentration in a blood sample is first located in the kinetic nomogram and then the dose corresponding to the area containing this location is read. Evaluation of performance and comparison with the traditional Bayesian procedure were done by a simulation study using the immunosuppressant drug sirolimus (rapamycin). All calculations were performed by use of Matlab software. RESULTS: The simulation study confirmed the need for individual dosage adjustment; 71.6% of individuals underwent modification of the identification protocol of 1 mg twice daily in order to reach steady-state trough concentrations of 8 ng/mL. When the regimens were adjusted by kinetic nomograms and the Bayesian procedure, the steady-state trough concentrations of sirolimus showed low variability (coefficients of variation [CVs] of 23.4% and 24.0%, respectively) as compared with those obtained by standard recommended protocols of 4 mg once daily (CV 68.6%). The doses adjusted by kinetic nomograms and the Bayesian procedure were linearly linked and highly correlated (r = 0.96), and both provided simultaneous control of minimum and maximum drug concentrations (63.9% and 68.7% of cases between 6 and 20 ng/mL, respectively). CONCLUSION: Kinetic nomograms allow rapid and reliable dosage adjustment after the start of drug therapy. They are interesting alternatives to the cumbersome Bayesian procedure, and they provide dosage adjustment even for drugs that exhibit large intraindividual variability. In the clinical context, kinetic nomograms render individual dosage adjustment a simplified bedside application, and they could assist population studies aiming at dose individualization. PMID- 22087865 TI - Effect of cytochrome P450 3A4 inducers on the pharmacokinetic, pharmacodynamic and safety profiles of bortezomib in patients with multiple myeloma or non Hodgkin's lymphoma. AB - BACKGROUND AND OBJECTIVE: Bortezomib, an antineoplastic agent with proteasome inhibitory activity, is extensively metabolized by the hepatic microsomal cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C19. Drugs that affect these enzymes may therefore have an impact on the pharmacological profile of bortezomib. This study evaluated the effects of co-administration of a potent CYP3A4 inducer (rifampicin [rifampin]) and a weak CYP3A4 inducer (dexamethasone) on the pharmacokinetic, pharmacodynamic and safety profiles of bortezomib. PATIENTS AND METHODS: Patients aged >=18 years with relapsed or refractory multiple myeloma or non-Hodgkin's lymphoma received intravenous bortezomib 1.3 mg/m2, administered on days 1, 4, 8 and 11 of a 21-day cycle, for 3 cycles. In stage 1, patients were randomized (1 : 1) to receive bortezomib alone or in combination with oral rifampicin 600 mg once daily on days 4-10 during cycle 3 only. If the mean area under the plasma concentration-time curve (AUC) of bortezomib was reduced by >=30% during rifampicin co-administration, then stage 2 was initiated, in which patients received bortezomib with dexamethasone 40 mg once daily on days 1-4 and days 9-12 during cycle 3 only. Blood samples were collected on days 11 through 14 of cycles 2 and 3 before and after bortezomib administration, at prespecified time points, for pharmacokinetic and pharmacodynamic (proteasome inhibition) assessments. RESULTS: Twelve patients in the bortezomib-alone arm, six patients in the bortezomib plus rifampicin arm and seven patients in the bortezomib plus dexamethasone arm were included in the pharmacokinetics-evaluable set. Rifampicin reduced the mean AUC from 0 to 72 hours (AUC(72h)) of bortezomib by approximately 45% (223 ng . h/mL in cycle 2 vs 123 ng . h/mL in cycle 3), while dexamethasone had no effect (mean AUC(72h): 179 ng . h/mL in cycle 2 vs 170 ng . h/mL in cycle 3). Proteasome inhibition parameters in peripheral blood were unaffected by rifampicin or dexamethasone. Safety profiles were similar across the treatment arms and consistent with previous experience of bortezomib. CONCLUSIONS: In patients with multiple myeloma or non-Hodgkin's lymphoma, co-administration of rifampicin decreased the exposure to bortezomib but did not affect the proteasome inhibition or safety profiles; co-administration of dexamethasone did not affect the exposure to bortezomib, proteasome inhibition or safety profiles. Concomitant administration of bortezomib with strong CYP3A4 inducers such as rifampicin is not recommended, as it may result in a reduction of the clinical effect, whereas concomitant administration of weak CYP3A4 inducers such as dexamethasone does not affect the pharmacological profile of bortezomib. PMID- 22087866 TI - Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis. AB - BACKGROUND AND OBJECTIVE: Inhibition of the receptor activator of nuclear factor kappa-B ligand (RANKL) is a therapeutic target for treatment of bone disorders associated with increased bone resorption, such as osteoporosis. The objective of this analysis was to characterize the population pharmacokinetics of denosumab (AMG 162; Prolia(r)), a fully human IgG2 monoclonal antibody that binds to RANKL, in healthy subjects and postmenopausal women with osteopenia or osteoporosis. METHODS: A total of 22944 serum free denosumab concentrations from 495 healthy subjects and 1069 postmenopausal women with osteopenia or osteoporosis were pooled. Denosumab was administered as either a single intravenous dose (n = 36), a single subcutaneous dose (n = 469) or multiple subcutaneous doses (n = 1059), ranging from 0.01 to 3 mg/kg (or 6-210 mg as fixed mass dosages), every 3 or 6 months for up to 48 months. An open, two-compartment pharmacokinetic model with a quasi-steady-state approximation of the target-mediated drug disposition model was used to describe denosumab pharmacokinetics, using NONMEM Version 7.1.0 software. Subcutaneous absorption was characterized by the first-order absorption rate constant (k(a)), with constant absolute bioavailability over the range of doses that were evaluated. Clearance and volume of distribution parameters were scaled by body weight, using a power model. Model evaluation was performed through visual predictive checks. RESULTS: The subcutaneous bioavailability of denosumab was 64%, and the k(a) was 0.00883 h-1. The central volume of distribution and linear clearance were 2.49 L/66 kg and 3.06 mL/h/66 kg, respectively. The baseline RANKL level, quasi-steady-state constant and RANKL degradation rate were 614 ng/mL, 138 ng/mL and 0.00148 h-1, respectively. Between subject variability in model parameters was moderate. A fixed dose of 60 mg provided RANKL inhibition similar to that achieved by equivalent body weight based dosing. The effects of age and race on the area under the serum concentration-time curve of denosumab were less than 15% over the range of covariate values that were evaluated. CONCLUSIONS: The non-linearity in denosumab pharmacokinetics is probably due to RANKL binding, and denosumab dose adjustment based on the patient demographics is not warranted. PMID- 22087868 TI - Population pharmacokinetic/pharmacodynamic analyses as the basis for dosing of therapeutic monoclonal antibodies. PMID- 22087867 TI - Application of a systems approach to the bottom-up assessment of pharmacokinetics in obese patients: expected variations in clearance. AB - BACKGROUND AND OBJECTIVES: The maintenance dose of a drug is dependent on drug clearance, and thus any biochemical and physiological changes in obesity that affect parameters such as cardiac output, renal function, expression of drug metabolizing enzymes and protein binding may result in altered clearance compared with that observed in normal-weight subjects (corrected or uncorrected for body weight). Because of the increasing worldwide incidence of obesity, there is a need for more information regarding the optimal dosing of drug therapy to be made available to prescribers. This is usually provided via clinical studies in obese people; however, such studies are not available for all drugs that might be used in obese subjects. Incorporation of the relevant physiological and biochemical changes into predictive bottom-up pharmacokinetic models in order to optimize dosage regimens may offer a logical way forward for the cases where no clinical data exist. The aims of the current report are to apply such a 'systems approach' to identify the likelihood of observing variations in the clearance of drugs in obesity and morbid obesity for a set of compounds for which clinical data, as well as the necessary in vitro information, are available, and to provide a framework for assessing other drugs in the future. METHODS: The population specific changes in demographic, physiological and biochemical parameters that are known to be relevant to obese and morbidly obese subjects were collated and incorporated into two separate population libraries. These libraries, together with mechanistic in vitro-in vivo extrapolations (IVIVE) within the Simcyp Population-based SimulatorTM, were used to predict the clearance of oral alprazolam, oral caffeine, oral chlorzoxazone, oral ciclosporin, intravenous and oral midazolam, intravenous phenytoin, oral theophylline and oral triazolam. The design of the simulated studies was matched as closely as possible with that of the clinical studies. Outcome was measured by the predicted ratio of the clearance of the drug in obese and lean subjects +/- its 90% confidence interval, compared with observed values. The overall statistical measures of the performance of the model to detect differences in compound clearance between obese and lean populations were investigated by measuring sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). A power calculation was carried out to investigate the impact of the sample size on the overall outcome of clinical studies. RESULTS: The model was successful in predicting clearance in obese subjects, with the degree to which simulations could mimic the outcome of in vivo studies being greater than 60% for six of the eight drugs. A clear difference in the clearance of chlorzoxazone was correctly picked up via simulation. The overall statistical measures of the performance of the Simcyp Simulator were 100% sensitivity, 66% specificity, 60% PPV and 100% NPV. Studies designed on the basis of the ratio of the absolute values required substantial numbers of participants in order to detect a significant difference, except for phenytoin and chlorzoxazone, where the ratios of the weight-normalized clearances generally showed statistically significant differences with a smaller number of subjects. CONCLUSION: Extension of a mechanistic predictive pharmacokinetic model to accommodate physiological and biochemical changes associated with obesity and morbid obesity allowed prediction of changes in drug clearance on the basis of in vitro data, with reasonable accuracy across a range of compounds that are metabolized by different enzymes. Prediction of the effects of obesity on drug clearance, normalized by various body size scalars, is of potential value in the design of clinical studies during drug development and in the introduction of dosage adjustments that are likely to be needed in clinical practice. PMID- 22087869 TI - Obesity and its impact on drug therapy: are we ready for this change? PMID- 22087871 TI - Histological analysis of surgical lumbar intervertebral disc tissue provides evidence for an association between disc degeneration and increased body mass index. AB - BACKGROUND: Although histopathological grading systems for disc degeneration are frequently used in research, they are not yet integrated into daily care routine pathology of surgical samples. Therefore, data on histopathological changes in surgically excised disc material and their correlation to clinical parameters such as age, gender or body mass index (BMI) is limited to date. The current study was designed to correlate major physico-clinical parameters from a population of orthopaedic spine center patients (gender, age and BMI) with a quantitative histologic degeneration score (HDS). METHODS: Excised lumbar disc material from 854 patients (529 men/325 women/mean age 56 (15-96) yrs.) was graded based on a previously validated histologic degeneration score (HDS) in a cohort of surgical disc samples that had been obtained for the treatment of either disc herniation or discogenic back pain. Cases with obvious inflammation, tumor formation or congenital disc pathology were excluded. The degree of histological changes was correlated with sex, age and BMI. RESULTS: The HDS (0-15 points) showed significantly higher values in the nucleus pulposus (NP) than in the annulus fibrosus (AF) (Mean: NP 11.45/AF 7.87), with a significantly higher frequency of histomorphological alterations in men in comparison to women. Furthermore, the HDS revealed a positive significant correlation between the BMI and the extent of histological changes. No statistical age relation of the degenerative lesions was seen. CONCLUSIONS: This study demonstrated that histological disc alterations in surgical specimens can be graded in a reliable manner based on a quantitative histologic degeneration score (HDS). Increased BMI was identified as a positive risk factor for the development of symptomatic, clinically significant disc degeneration. PMID- 22087872 TI - Pathogenesis and phylogenetic analyses of canine distemper virus strain ZJ7 isolate from domestic dogs in China. AB - A new isolate of canine distemper virus (CDV), named ZJ7, was isolated from lung tissues of a dog suspected with CDV infection using MDCK cells. The ZJ7 isolate induced cytopathogenic effects of syncytia in MDCK cell after six passages. In order to evaluate pathogenesis of ZJ7 strain, three CDV sero-negative dogs were intranasally inoculated with its virus suspension. All infected dogs developed clinical signs of severe bloody diarrhea, conjunctivitis, ocular discharge, nasal discharge and coughing, fever and weight loss at 21 dpi, whereas the mock group infected with DMEM were normal. The results demonstrated that CDV-ZJ7 strain isolated by MDCK cell was virulent, and the nucleotide and amino acid sequences of strain ZJ7 had no change after isolation by MDCK cell when compared with the original virus from the fresh tissues. Molecular and phylogenetic analyses for the nucleocapsid (N), phosphoprotein (P) and receptor binding haemagglutinin (H) gene of the ZJ7 isolate clearly showed it is joins to the Asia 1 group cluster of CDV strains, the predominant genotype in China. PMID- 22087874 TI - Biopharmaceutical evaluation of diclofenac sodium controlled release tablets prepared from gum karaya--chitosan polyelectrolyte complexes. AB - The phenomena of polymer interactions and formation of polyelectrolyte complexes (PECs) of oppositely charged polymers have been the focus of interest in fundamental and applied research. Such PECs may possess unique properties that are different from those of individual polymers. In the present study, attempts were made to prepare PECs of negative colloid gum karaya (GK) and positively charged polysaccharide chitosan (CH). The association and factors affecting the interactions between GK and CH were studied by pH and conductivity studies. The dried complexes were characterized by X-ray diffraction, Fourier transformed Infrared (FTIR) Spectroscopy, Scanning Electron Microscopy. The PECs were utilized for encapsulation of diclofenac sodium. Selected polyelectrolyte microparticles were compressed into tablets and were compared with commercial sustained release product Voveran SR(r). Positive results of the study indicated the applicability of PECs in the design of oral controlled release drug delivery systems. PMID- 22087873 TI - Functional coupling analysis suggests link between the obesity gene FTO and the BDNF-NTRK2 signaling pathway. AB - BACKGROUND: The Fat mass and obesity gene (FTO) has been identified through genome wide association studies as an important genetic factor contributing to a higher body mass index (BMI). However, the molecular context in which this effect is mediated has yet to be determined. We investigated the potential molecular network for FTO by analyzing co-expression and protein-protein interaction databases, Coxpresdb and IntAct, as well as the functional coupling predicting multi-source database, FunCoup. Hypothalamic expression of FTO-linked genes defined with this bioinformatics approach was subsequently studied using quantitative real time-PCR in mouse feeding models known to affect FTO expression. RESULTS: We identified several candidate genes for functional coupling to FTO through database studies and selected nine for further study in animal models. We observed hypothalamic expression of Profilin 2 (Pfn2), cAMP dependent protein kinase catalytic subunit beta (Prkacb), Brain derived neurotrophic factor (Bdnf), neurotrophic tyrosine kinase, receptor, type 2 (Ntrk2), Signal transducer and activator of transcription 3 (Stat3), and Btbd12 to be co-regulated in concert with Fto. Pfn2 and Prkacb have previously not been linked to feeding regulation. CONCLUSIONS: Gene expression studies validate several candidates generated through database studies of possible FTO interactors. We speculate about a wider functional role for FTO in the context of current and recent findings, such as in extracellular ligand-induced neuronal plasticity via NTRK2/BDNF, possibly via interaction with the transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta). PMID- 22087875 TI - A mechanistic study on the amidation of esters mediated by sodium formamide. AB - Kinetic and computational studies on the amidation of esters with mixtures of formamide and sodium methoxide are described. Rate studies are consistent with a fast deprotonation of formamide followed by two reversible acyl transfers affected by solvent participation. MP2 calculations suggest that the first acyl transfer between the ester and sodium formamide is rate-determining. The transition structures leading to the formation and collapse of the first tetrahedral intermediate are calculated to be isoenergetic. PMID- 22087876 TI - Investigation of the role of hydrophilic chain length in amphiphilic perfluoropolyether/poly(ethylene glycol) networks: towards high-performance antifouling coatings. AB - The facile preparation of amphiphilic network coatings having a hydrophobic dimethacryloxy-functionalized perfluoropolyether (PFPE-DMA; M(w) = 1500 g mol( 1)) crosslinked with hydrophilic monomethacryloxy functionalized poly(ethylene glycol) macromonomers (PEG-MA; M(w) = 300, 475, 1100 g mol(-1)), intended as non toxic high-performance marine coatings exhibiting antifouling characteristics is demonstrated. The PFPE-DMA was found to be miscible with the PEG-MA. Photo-cured blends of these materials containing 10 wt% of PEG-MA oligomers did not swell significantly in water. PFPE-DMA crosslinked with the highest molecular weight PEG oligomer (ie PEG1100) deterred settlement (attachment) of algal cells and cypris larvae of barnacles compared to a PFPE control coating. Dynamic mechanical analysis of these networks revealed a flexible material. Preferential segregation of the PEG segments at the polymer/air interface resulted in enhanced antifouling performance. The cured amphiphilic PFPE/PEG films showed decreased advancing and receding contact angles with increasing PEG chain length. In particular, the PFPE/PEG1100 network had a much lower advancing contact angle than static contact angle, suggesting that the PEG1100 segments diffuse to the polymer/water interface quickly. The preferential interfacial aggregation of the larger PEG segments enables the coating surface to have a substantially enhanced resistance to settlement of spores of the green seaweed Ulva, cells of the diatom Navicula and cypris larvae of the barnacle Balanus amphitrite as well as low adhesion of sporelings (young plants) of Ulva, adhesion being lower than to a polydimethyl elastomer, Silastic T2. PMID- 22087878 TI - Subwavelength imaging using phase-conjugating nonlinear nanoantenna arrays. AB - We investigate the use of nonlinear metasurfaces formed by plasmonic nanoantennas loaded with chi(3) nonlinear elements, in order to realize subwavelength imaging based on phase conjugation and time reversal. The nanoantennas' plasmonic resonance is used to boost the nonlinear response over an ultrathin surface, meeting the conditions for efficient phase conjugation necessary for imaging applications. Pairing two such surfaces, we put forward a realistic design for a time-reversal 'perfect lens', which can overcome the limitations in resolution and sensitivity to losses typical of negative-index lenses. PMID- 22087877 TI - Hypoxia acts through multiple signaling pathways to induce metallothionein transactivation by the metal-responsive transcription factor-1 (MTF-1). AB - Metal-responsive transcription factor-1 (MTF-1) is essential for the induction of genes encoding metallothionein by metals and hypoxia. Here, we studied the mechanism controlling the activation of MTF-1 by hypoxia. Hypoxia activation of Mt gene transcription is dependent on the presence of metal regulatory elements (MREs) in the promoter of Mt genes. We showed that MREa and MREd are the main elements controlling mouse Mt-1 gene induction by hypoxia. Transfection experiments in Mtf-1-null cells showed that MTF-1 is essential for induction by hypoxia. Chromatin immunoprecipitation analysis showed that MTF-1 DNA-binding activity was strongly enhanced in the presence of zinc but not by hypoxia. Notably, hypoxia inducible factor- (HIF) 1alpha was recruited to the Mt-1 promoter in response to hypoxia but not to zinc. MTF-1 activation was inhibited by PKC, JNK, and PI3K inhibitors and by the electron transport chain inhibitors rotenone and myxothiazol, but not by the antioxidant N-acetylcysteine. We showed that prolyl-hydroxylase inhibitors can activate MTF-1, but this activation requires the presence of HIF-1alpha. Finally, HIF-dependent transcription is enhanced in the presence of MTF-1 and induction of an MRE promoter is stimulated by HIF-1alpha, thus indicating cooperation between these 2 factors. However, coimmunoprecipitation experiments did not suggest direct interaction between MTF 1 and HIF-1alpha. PMID- 22087879 TI - Motion of light adatoms and molecules on the surface of few-layer graphene. AB - Low-voltage aberration-corrected transmission electron microscopy (TEM) is applied to investigate the feasibility of continuous electron beam cleaning of graphene and monitor the removal of residual species as present on few-layer graphene (FLG) surfaces. This combined approach allows us to detect light adatoms and evaluate their discontinuous sporadic motional behavior. Furthermore, the formation and dynamic behavior of isolated molecules on the FLG surface can be captured. The preferential source of adatoms and adsorbed molecules appeared to be carbonaceous clusters accumulated from residual solvents on the graphene surface. TEM image simulations provide potential detail on the observed molecular structures. Molecular dynamics simulations confirm the experimentally observed dynamics occurring on the energy scale imposed by the presence of the 80 kV electron beam and help elucidate the underlying mechanisms. PMID- 22087880 TI - Customary adolescent sexual practices among the Akha of northern Lao PDR: considerations for public health. AB - Based on interviews and focus group discussions conducted in northern Laos, this study explores Akha understandings of customary first pre-pubertal sex acts, a thonh thong ('break through vagina' [BV]) for girls and yaha heu ('open foreskin' [OF]) for boys, which are thought to enable the maturing of bodies into adulthood. The study also examines the practice of a thor ta yang ('Welcome Guest') in which sexually initiated girls have sex with male visitors to Akha villages. The study found that many young women experience BV as painful and traumatic. However, since all Akha in the study 'knew' that young bodies will not mature into attractive, healthy adults if they do not perform BV and OF, attitudes were largely positive. Both men and women are at increasing risk of STIs, including HIV, since resettlement and an influx of non-Akha into the area. We conclude that Akha villagers should be included in the planning of future public health strategies that do not violate their cultural commitments and dignity but that help them resist potential exploitation and threats to their health. Such strategies might include sexual education programs and encouraging the delay of BV and OF. PMID- 22087881 TI - Gated photochromism in triarylborane-containing dithienylethenes: a new approach to a "lock-unlock" system. AB - Photochromic inactive dithienylethene derivatives appended with 3- or 5 dimesitylboryl-2,2'-bithiophene have been synthesized. Upon fluoride ion-binding, the photochromic reactivity is "unlocked", displaying a novel gated photochromic property. PMID- 22087882 TI - Character of devitrification, viewed from enthalpic paths, of the vapor-deposited ethylbenzene glasses. AB - Enthalpic path and enthalpy-relaxation rates of ethylbenzene glasses prepared by vapor deposition at various temperatures, T(D), were examined on heating intermittently with a high-precision adiabatic calorimeter. It was confirmed that when T(D) is in the range 0.79-0.96T(g), the enthalpies elucidated at their preparation temperatures, i.e., T(D), are lower than those of the liquid-cooled glass. The fictive temperature T(f) at which the enthalpy path of each glass crosses the enthalpy curve expected for the equilibrium supercooled liquid was observed to be lowest when T(D) = 0.92T(g) = 105 K. The glasses revealed two remarkable characteristics: first, the temperature of the peak in the endothermic effect, which corresponds to the temperature T(g,dev) of the steepest devitrification, was observed to increase in correlation with the low-enthalpic nature of the glasses. Second, the devitrification manner was quite different between the glasses with T(D) < 0.92T(g) and T(D) >= 0.92T(g), even if the two glasses have the same T(f); the former devitrified gradually and the latter relatively sharply. PMID- 22087883 TI - Effect of haemolysis and repeated freeze-thawing cycles on wild boar serum antibody testing by ELISA. AB - BACKGROUND: Monitoring wildlife diseases is needed to identify changes in disease occurrence. Wildlife blood samples are valuable for this purpose but are often gathered haemolysed. To maximise information, sera often go through repeated analysis and freeze-thaw cycles. Herein, we used samples of clean and haemolysed Eurasian wild boar (Sus scrofa) serum stored at -20 degrees C and thawed up to five times to study the effects of both treatments on the outcome of a commercial ELISA test for the detection of antibodies against Suid Herpesvirus 1 (ADV). RESULTS: The estimated prevalence of antibodies against ADV was 50-53% for clean and haemolysed sera. Hence, haemolysis did not reduce the mean observed serum antibody prevalence. However, 10 samples changed their classification after repeated freeze-thawing. This included 3 (15%) of the clean sera and 7 (41%) of the haemolysed sera. CONCLUSIONS: We recommend (1) establishing more restrictive cut-off values when testing wildlife sera, (2) recording serum quality prior to sample banking, (3) recording the number of freezing-thawing cycles and (4) store sera in various aliquots to reduce repeated usage. For instance, sera with more than 3 freeze-thaw cycles and a haemolysis of over 3 on a scale of 4 should better be discarded for serum antibody monitoring. Even clean (almost not haemolysed) sera should not go through more than 5 freeze-thaw cycles. PMID- 22087885 TI - A laboratory training model using fresh sheep spines for pedicular screw fixation. AB - BACKGROUND: Laboratory training models are essential for developing and refining surgical skills prior to clinical application of spinal surgery. A simple simulation model is needed for young residents to learn how to handle instruments and to perform safe posterior lumbar approaches. Our aim is to present a practical laboratory model using a fresh sheep lumbar spine that simulates the pedicular screw fixation in spine surgery. METHODS: The material consists of a fresh cadaveric spine from a 2-year-old sheep. A two-step approach was designed for posterior lumbar approaches including placement of lumbar pedicular screws. RESULTS: The model simulates standard posterior lumbar pedicular screw fixation of the human spine. CONCLUSIONS: The cadaveric sheep spine represents a useful method to accustom trainees of neurosurgery and spine surgery residents and simulates posterior lumbar pedicular screw fixation performed in the human spine. PMID- 22087884 TI - A framework and a measurement instrument for sustainability of work practices in long-term care. AB - BACKGROUND: In health care, many organizations are working on quality improvement and/or innovation of their care practices. Although the effectiveness of improvement processes has been studied extensively, little attention has been given to sustainability of the changed work practices after implementation. The objective of this study is to develop a theoretical framework and measurement instrument for sustainability. To this end sustainability is conceptualized with two dimensions: routinization and institutionalization. METHODS: The exploratory methodological design consisted of three phases: a) framework development; b) instrument development; and c) field testing in former improvement teams in a quality improvement program for health care (N teams = 63, N individual = 112). Data were collected not until at least one year had passed after implementation.Underlying constructs and their interrelations were explored using Structural Equation Modeling and Principal Component Analyses. Internal consistency was computed with Cronbach's alpha coefficient. A long and a short version of the instrument are proposed. RESULTS: The chi2- difference test of the -2 Log Likelihood estimates demonstrated that the hierarchical two factor model with routinization and institutionalization as separate constructs showed a better fit than the one factor model (p < .01). Secondly, construct validity of the instrument was strong as indicated by the high factor loadings of the items. Finally, the internal consistency of the subscales was good. CONCLUSIONS: The theoretical framework offers a valuable starting point for the analysis of sustainability on the level of actual changed work practices. Even though the two dimensions routinization and institutionalization are related, they are clearly distinguishable and each has distinct value in the discussion of sustainability. Finally, the subscales conformed to psychometric properties defined in literature. The instrument can be used in the evaluation of improvement projects. PMID- 22087886 TI - Implementing an exact finite boundary integral equation method for finite rough surfaces (L). AB - An exact integral equation approach to solving scattering from a finite section of roughness in an otherwise infinitely flat surface was described in DeSanto and Martin [J. Acoust. Soc. Am. 102, 67-77]. In this letter, the details of a numerical implementation of this approach are presented for a rough pressure release surface. An example comparing the results from this method to those from a standard, truncated integral approach is given. PMID- 22087887 TI - Measuring static thermal permeability and inertial factor of rigid porous materials (L). AB - An acoustic method based on sound transmission is proposed for deducing the static thermal permeability and the inertial factor of porous materials having a rigid frame at low frequencies. The static thermal permeability of porous material is a geometrical parameter equal to the inverse trapping constant of the solid frame [Lafarge et al., J. Acoust. Soc. Am. 102, 1995 (1997)] and is an important characteristic of the porous material. The inertial factor [Norris., J. Wave Mat. Interact. 1, 365 (1986)] describes the fluid structure interactions in the low frequency range (1-3 kHz). The proposed method is based on a temporal model of the direct and inverse scattering problems for the propagation of transient audible frequency waves in a homogeneous isotropic slab of porous material having a rigid frame. The static thermal permeability and the inertial factor are determined from the solution of the inverse problem. The minimization between experiment and theory is made in the time domain. Tests are performed using industrial plastic foams. Experimental and theoretical data are in good agreement. Furthermore, the prospects are discussed. This method has the advantage of being simple, rapid, and efficient. PMID- 22087888 TI - The influence of actual and imputed talker gender on fricative perception, revisited (L). AB - To examine the role of perceived gender on fricative identification, a study was conducted in which listeners identified /s/-/?/ and /s/-/theta/ continua combined with vowels produced by a man and a woman. These were acoustically modified to be consistent with different-sized vocal tracts (VT), and were presented with pictures of men or women. Listeners identified more tokens of /s/ in the /s/-/?/ and more tokens of /theta/ in the /s/-/theta/ continuum when these sounds were combined with men's vowels, with vowels consistent with a 17 cm VT, and with pictures of men. Results support the hypothesis that listeners incorporate information about talker gender during fricative perception. PMID- 22087889 TI - The effect of temporal asymmetry on amplitude modulation detection using pure tone carriers (L). AB - The effect of temporal asymmetry on amplitude modulation detection was studied using sawtooth modulators with rising (ramped) or falling (damped) temporal envelopes within each period of modulation. For pure-tone carriers, damped modulation was more detectable than ramped modulation for a 5-kHz carrier (by a threshold difference of 3.2 dB on average) but not for a 1-kHz carrier. The threshold difference obtained at 5 kHz between the ramped and damped modulators was consistent across modulation rates (8-128 Hz). This carrier frequency dependence suggests that the effect of temporally asymmetry on modulation detection originates from envelope-based, within-channel mechanisms. PMID- 22087890 TI - Experimental source characterization techniques for studying the acoustic properties of perforates under high level acoustic excitation. AB - This paper discusses experimental techniques for obtaining the acoustic properties of in-duct samples with non-linear acoustic characteristic. The methods developed are intended both for studies of non-linear energy transfer to higher harmonics for samples only accessible from one side such as wall treatment in aircraft engine ducts or automotive exhaust systems and for samples accessible from both sides such as perforates or other top sheets. When harmonic sound waves are incident on the sample nonlinear energy transfer results in sound generation at higher harmonics at the sample (perforate) surface. The idea is that these sources can be characterized using linear system identification techniques similar to one-port or two-port techniques which are traditionally used for obtaining source data for in-duct sources such as IC-engines or fans. The starting point will be so called polyharmonic distortion modeling which is used for characterization of nonlinear properties of microwave systems. It will be shown how acoustic source data models can be expressed using this theory. Source models of different complexity are developed and experimentally tested. The results of the experimental tests show that these techniques can give results which are useful for understanding non-linear energy transfer to higher harmonics. PMID- 22087891 TI - Nonlinear progressive wave equation for stratified atmospheres. AB - The nonlinear progressive wave equation (NPE) [McDonald and Kuperman, J. Acoust. Soc. Am. 81, 1406-1417 (1987)] is expressed in a form to accommodate changes in the ambient atmospheric density, pressure, and sound speed as the time-stepping computational window moves along a path possibly traversing significant altitude differences (in pressure scale heights). The modification is accomplished by the addition of a stratification term related to that derived in the 1970s for linear range-stepping calculations and later adopted into Khokhlov-Zabolotskaya Kuznetsov-type nonlinear models. The modified NPE is shown to preserve acoustic energy in a ray tube and yields analytic similarity solutions for vertically propagating N waves in isothermal and thermally stratified atmospheres. PMID- 22087892 TI - High-accuracy acoustic detection of nonclassical component of material nonlinearity. AB - The aim is to assess the nonclassical component of material nonlinearity in several classes of materials with weak, intermediate, and high nonlinear properties. In this contribution, an optimized nonlinear resonant ultrasound spectroscopy (NRUS) measuring and data processing protocol applied to small samples is described. The protocol is used to overcome the effects of environmental condition changes that take place during an experiment, and that may mask the intrinsic nonlinearity. External temperature fluctuation is identified as a primary source of measurement contamination. For instance, a variation of 0.1 degrees C produced a frequency variation of 0.01%, which is similar to the expected nonlinear frequency shift for weakly nonlinear materials. In order to overcome environmental effects, the reference frequency measurements are repeated before each excitation level and then used to compute nonlinear parameters. Using this approach, relative resonant frequency shifts of 10(-5) can be measured, which is below the limit of 10(-4) often considered as the limit of NRUS sensitivity under common experimental conditions. Due to enhanced sensitivity resulting from the correction procedure applied in this work, nonclassical nonlinearity in materials that before have been assumed to only be classically nonlinear in past work (steel, brass, and aluminum) is reported. PMID- 22087893 TI - Whistling of an orifice in a reverberating duct at low Mach number. AB - An experimental investigation of the parameters controlling the whistling frequency and amplitude of an orifice in a confined turbulent flow is undertaken. A circular single hole orifice with sharp edges, a hole diameter equal to 0.015 m and a thickness equal to 0.005 m, is arranged in an air test rig with an inner diameter equal to 0.03 m. The Mach number ranges around 0.02 and the Reynolds number around 10(4). Variable reflecting boundary conditions are arranged upstream and downstream, and several flow velocities are tested. It is found that the Bode-Nyquist criterion accurately predicts the conditions of self-sustained oscillation and the value of the whistling frequency. Furthermore, it is found that the acoustic velocity in whistling regime varies from 1% to 15% of the steady flow velocity, and that it depends on the overall acoustic reflection of the surrounding pipe and on the Strouhal number. PMID- 22087894 TI - A nonlocal effective operator for coupling forward and backward propagating modes in inhomogeneous media. AB - In an acoustic waveguide spatial inhomogeneities couple the forward and backward propagating modal amplitudes. To address the nature of such coupling the integral equation for the range-dependent modal amplitudes is decomposed into components that satisfy the asymptotic boundary conditions of the free Green's function operator. An equivalent set of equations is obtained by eliminating the components that become the asymptotically backward propagating channels to leave a set of integral equations that describe only the components that become asymptotically the forward propagating channels. The elimination of the components that become asymptotically the backward propagating channels is done at the expense of introducing a nonlocal effective coupling operator. The nonlocal operator contains all the effects of the asymptotically backward propagating field on the asymptotically forward propagating field. An expansion of the effective coupling operator allows an investigation of the importance of the coupling and provides a systematic approach to add correction terms to the forward only equation. Idealistic underwater waveguides with various degrees of inhomogeneities are used to illustrate the main features of the convergence characteristics for the expansion. PMID- 22087895 TI - Experimental testing of the variable rotated elastic parabolic equation. AB - A series of laboratory experiments was conducted to obtain high-quality data for acoustic propagation in shallow water waveguides with sloping elastic bottoms. Accurate modeling of transmission loss in these waveguides can be performed with the variable rotated parabolic equation method. Results from an earlier experiment with a flat or sloped slab of polyvinyl chloride (PVC) demonstrated the necessity of accounting for elasticity in the bottom and the ability of the model to produce benchmark-quality agreement with experimental data [J. M. Collis et al., J. Acoust. Soc. Am. 122, 1987-1993 (2007)]. This paper presents results of a second experiment, using two PVC slabs joined at an angle to create a waveguide with variable bottom slope. Acoustic transmissions over the 100-300 kHz band were received on synthetic horizontal arrays for two source positions. The PVC slabs were oriented to produce three different simulated waveguides: flat bottom followed by downslope, upslope followed by flat bottom, and upslope followed by downslope. Parabolic equation solutions for treating variable slopes are benchmarked against the data. PMID- 22087896 TI - Extension of the angular spectrum method to calculate pressure from a spherically curved acoustic source. AB - The angular spectrum method is an accurate and computationally efficient method for modeling acoustic wave propagation. The use of the typical 2D fast Fourier transform algorithm makes this a fast technique but it requires that the source pressure (or velocity) be specified on a plane. Here the angular spectrum method is extended to calculate pressure from a spherical transducer-as used extensively in applications such as magnetic resonance-guided focused ultrasound surgery-to a plane. The approach, called the Ring-Bessel technique, decomposes the curved source into circular rings of increasing radii, each ring a different distance from the intermediate plane, and calculates the angular spectrum of each ring using a Fourier series. Each angular spectrum is then propagated to the intermediate plane where all the propagated angular spectra are summed to obtain the pressure on the plane; subsequent plane-to-plane propagation can be achieved using the traditional angular spectrum method. Since the Ring-Bessel calculations are carried out in the frequency domain, it reduces calculation times by a factor of approximately 24 compared to the Rayleigh-Sommerfeld method and about 82 compared to the Field II technique, while maintaining accuracies of better than 96% as judged by those methods for cases of both solid and phased-array transducers. PMID- 22087897 TI - Evidence of the harmonic Faraday instability in ultrasonic atomization experiments with a deep, inviscid fluid. AB - A popular method for generating micron-sized aerosols is to submerge ultrasonic (omega~MHz) piezoelectric oscillators in a water bath. The submerged oscillator atomizes the fluid, creating droplets with radii proportional to the wavelength of the standing wave at the fluid surface. Classical theory for the Faraday instability predicts a parametric instability driving a capillary wave at the subharmonic (omega/2) frequency. For many applications it is desirable to reduce the size of the droplets; however, using higher frequency oscillators becomes impractical beyond a few MHz. Observations are presented that demonstrate that smaller droplets may also be created by increasing the driving amplitude of the oscillator, and that this effect becomes more pronounced for large driving frequencies. It is shown that these observations are consistent with a transition from droplets associated with subharmonic (omega/2) capillary waves to harmonic (omega) capillary waves induced by larger driving frequencies and amplitudes, as predicted by a stability analysis of the capillary waves. PMID- 22087898 TI - Forced vibrations of a bubble in a liquid-filled elastic vessel. AB - There is increasing demand for accurate characterization of the in vivo behavior of microbubble agents used for ultrasound imaging and therapy. This study examines bubble-vessel interaction, in particular the propagation of disturbances along the vessel wall. Finite element simulations of a 3 MUm radius microbubble suspended in a viscous liquid and enclosed in a 4 MUm radius elastic vessel were performed, and the results compared with existing analytical results for wave propagation in elastic liquid-filled tubes. The vessel wall was shown to have a significant effect upon the amplitude of bubble oscillation and hence acoustic radiation from it, as well as distension of the vessel wall. It was found that the most important factor was the ratio of the excitation frequency to the natural "ring" frequency of the vessel which in turn depends upon its dimensions and mechanical properties. As this ratio increases, the motion of the vessel wall becomes increasingly localized to the site of the bubble. It was also shown that the validity of the results obtained using the applied model of vessel elasticity is limited to frequencies below the ring frequency, and this should be taken into account in the development of protocols for ultrasound safety and/or therapeutic procedures. PMID- 22087899 TI - Study of acoustic field modulation in the regenerator by double loudspeakers method. AB - A model to modulate acoustic field in a regenerator of a thermoacoustic system by the double loudspeakers method is presented in this paper. The equations are derived for acoustic field modulation. They represent the relations among acoustic field (complex pressure p(0), complex velocity u(0), and acoustic impedance Z(0)), driving parameters of loudspeakers (voltage amplitude and its phase difference), and operating parameters involved in a matrix H (frequency, temperature of regenerator). The range of acoustic field is adjustable and limited by the maximal driving voltages of loudspeakers according to driving parameters. The range is simulated and analyzed in the amplitude-phase and complex coordinate planes for a given or variable H. The simulated results indicate that the range has its intrinsic characteristics. The expected acoustic field in a regenerator can be obtained feasibly by the modulation. PMID- 22087900 TI - Two-dimensional virtual array for ultrasonic nondestructive evaluation using a time-reversal chaotic cavity. AB - Despite its introduction more than a decade ago, a two-dimensional ultrasonic array remains a luxury in nondestructive evaluation because of the complexity and cost associated with its fabrication and operation. This paper describes the construction and performance of a two-dimensional virtual array that solves these problems. The virtual array consists of only two transducers (one each for transmit and receive) and an aluminum chaotic cavity, augmented by a 10 * 10 matrix array of rectangular rods. Each rod, serving as an elastic waveguide, is calibrated to emit a collimated pulsed sound beam centered at 2.5 MHz using the reciprocal time reversal. The resulting virtual array is capable of pulse-echo interrogation of a solid sample in direct contact along 10 * 10 scan lines. Three-dimensional imaging of an aluminum test piece, the nominal thickness of which is in the order of 1 cm, is successfully carried out using the virtual array. PMID- 22087901 TI - Theoretical and experimental study of the nonlinear resonance vibration of cementitious materials with an application to damage characterization. AB - This paper presents a theoretical and experimental study of the nonlinear flexural vibration of a cement-based material with distributed microcracks caused by an important deterioration mechanism, alkali-silica reaction (ASR). The general equation of motion is derived for the flexural vibration of a slender beam with the nonlinear hysteretic constitutive relationship for consolidated materials, and then an approximate formula for excitation-dependent resonance frequency is obtained. A downward shift of the resonance frequency is related to the nonlinearity parameters defined in the constitutive relationship. Vibration experiments are conducted on standard mortar bar samples undergoing progressive ASR damage. The absolute nonlinearity parameters are determined from these experimental results using the theoretical solution in order to investigate their dependence on the damage state of the material. With the progress of the ASR damage, the absolute value of the hysteresis nonlinearity parameter increases by as much as six times from the intact (undamaged) state in the sample with highly reactive aggregate; this is in contrast to a change of about 16% in the linear resonance frequency. It is demonstrated that the combined theoretical and experimental approach developed in this research can be used to quantitatively characterize ASR damage in mortar samples and other cement-based materials. PMID- 22087902 TI - Band structures of phononic-crystal plates in the form of a sandwich-layered structure. AB - This study investigates the propagation of Lamb waves in phononic-crystal plates in the form of a sandwich-layered structure. The composite plates are composed of periodic layers bilaterally deposited on both sides of the homogeneous core layer. Using the analyses of the band structures and the transmission spectra, it is revealed that the core layer may induce significant modulations to the lower order Lamb modes. The modulations are ascribed to the reshaped particle displacement fields of the eigenmodes. Prominently, the core layer made of soft material (rubber) combines the identical eigenmodes of the periodic layers into a pair of asymmetric and symmetric modes in which case the periodic layers vibrate independently. However, the core layer made of hard material (tungsten) or medium hardness material (silicon) couples the periodic layers tightly, in which case the composites vibrate as a whole. In addition, it is found that the phononic band gaps are very sensitive to the thickness of the core layer; this could be indispensable to practical applications such as bandgap tuning. PMID- 22087903 TI - Matryoshka locally resonant sonic crystal. AB - The results of numerical modeling of sonic crystals with resonant array elements are reported. The investigated resonant elements include plain slotted cylinders as well as their various combinations, in particular, Russian doll or Matryoshka configurations. The acoustic band structure and transmission characteristics of such systems have been computed with the use of finite element methods. The general concept of a locally resonant sonic crystal is proposed that utilizes acoustic resonances to form additional band gaps that are decoupled from Bragg gaps. An existence of a separate attenuation mechanism associated with the resonant elements that increases performance in the lower frequency regime has been identified. The results show a formation of broad band gaps positioned significantly below the first Bragg frequency. For low frequency broadband attenuation, a most optimal configuration is the Matryoshka sonic crystal, where each scattering unit is composed of multiple concentric slotted cylinders. This system forms numerous gaps in the lower frequency regime, below Bragg bands, while maintaining a reduced crystal size viable for noise barrier technology. The finding opens alternative perspectives for the construction of sound barriers in the low frequency range usually inaccessible by traditional means including conventional sonic crystals. PMID- 22087904 TI - MP3 player listening sound pressure levels among 10 to 17 year old students. AB - Using a manikin, equivalent free-field sound pressure level measurements were made from the portable digital audio players of 219 subjects, aged 10 to 17 years (93 males) at their typical and "worst-case" volume levels. Measurements were made in different classrooms with background sound pressure levels between 40 and 52 dBA. After correction for the transfer function of the ear, the median equivalent free field sound pressure levels and interquartile ranges (IQR) at typical and worst-case volume settings were 68 dBA (IQR = 15) and 76 dBA (IQR = 19), respectively. Self-reported mean daily use ranged from 0.014 to 12 h. When typical sound pressure levels were considered in combination with the average daily duration of use, the median noise exposure level, Lex, was 56 dBA (IQR = 18) and 3.2% of subjects were estimated to exceed the most protective occupational noise exposure level limit in Canada, i.e., 85 dBA Lex. Under worst case listening conditions, 77.6% of the sample was estimated to listen to their device at combinations of sound pressure levels and average daily durations for which there is no known risk of permanent noise-induced hearing loss, i.e., <= 75 dBA Lex. Sources and magnitudes of measurement uncertainties are also discussed. PMID- 22087905 TI - Acoustical properties of double porosity granular materials. AB - Granular materials have been conventionally used for acoustic treatment due to their sound absorptive and sound insulating properties. An emerging field is the study of the acoustical properties of multiscale porous materials. An example of these is a granular material in which the particles are porous. In this paper, analytical and hybrid analytical-numerical models describing the acoustical properties of these materials are introduced. Image processing techniques have been employed to estimate characteristic dimensions of the materials. The model predictions are compared with measurements on expanded perlite and activated carbon showing satisfactory agreement. It is concluded that a double porosity granular material exhibits greater low-frequency sound absorption at reduced weight compared to a solid-grain granular material with similar mesoscopic characteristics. PMID- 22087906 TI - Temporal-envelope constancy of speech in rooms and the perceptual weighting of frequency bands. AB - Three experiments measured constancy in speech perception, using natural-speech messages or noise-band vocoder versions of them. The eight vocoder-bands had equally log-spaced center-frequencies and the shapes of corresponding "auditory" filters. Consequently, the bands had the temporal envelopes that arise in these auditory filters when the speech is played. The "sir" or "stir" test-words were distinguished by degrees of amplitude modulation, and played in the context; "next you'll get _ to click on." Listeners identified test-words appropriately, even in the vocoder conditions where the speech had a "noise-like" quality. Constancy was assessed by comparing the identification of test-words with low or high levels of room reflections across conditions where the context had either a low or a high level of reflections. Constancy was obtained with both the natural and the vocoded speech, indicating that the effect arises through temporal envelope processing. Two further experiments assessed perceptual weighting of the different bands, both in the test word and in the context. The resulting weighting functions both increase monotonically with frequency, following the spectral characteristics of the test-word's [s]. It is suggested that these two weighting functions are similar because they both come about through the perceptual grouping of the test-word's bands. PMID- 22087907 TI - Focusing of longitudinal ultrasonic waves in air with an aperiodic flat lens. AB - Modeling and experimental results of an ultrasonic aperiodic flat lens for use in air are presented. Predictive modeling of the lens is performed using a hybrid genetic-greedy algorithm constrained to a linear structure. The optimized design parameters are used to fabricate a lens. A method combining a fiber-disk arrangement and scanning laser vibrometer measurements is developed to characterize the acoustic field distribution generated by the lens. The focal spot size is determined to be 0.88 of the incident wavelength of 80-90 kHz at a distance of 2.5 mm from the lens. Theoretically computed field distributions, optimized frequency of operation, and spatial resolution focal length are compared with experimental measurements. The differences between experimental measurements and the theoretical computations are analyzed. The theoretical calculation of the focal spot diameter is 1.7 mm which is 48% of the experimental measurement at a frequency of 80-90 kHz. This work illustrates the capabilities of a hybrid algorithm approach to design of flat acoustic lenses to operate in air with a resolution of greater than the incident wavelength and the challenges of characterizing acoustic field distribution in air. PMID- 22087908 TI - Optimum array design to maximize Fisher information for bearing estimation. AB - Source bearing estimation is a common application of linear sensor arrays. The Cramer-Rao bound (CRB) sets a lower bound on the achievable mean square error (MSE) of any unbiased bearing estimate. In the spatially white noise case, the CRB is minimized by placing half of the sensors at each end of the array. However, many realistic ocean environments have a mixture of both white noise and spatially correlated noise. In shallow water environments, the correlated ambient noise can be modeled as cylindrically isotropic. This research designs a fixed aperture linear array to maximize the bearing Fisher information (FI) under these noise conditions. The FI is the inverse of the CRB, so maximizing the FI minimizes the CRB. The elements of the optimum array are located closer to the array ends than uniform spacing, but are not as extreme as in the white noise case. The optimum array results from a trade off between maximizing the array bearing sensitivity and minimizing output noise power variation over the bearing. Depending on the source bearing, the resulting improvement in MSE performance of the optimized array over a uniform array is equivalent to a gain of 2-5 dB in input signal-to-noise ratio. PMID- 22087909 TI - Wave field synthesis of moving virtual sound sources with complex radiation properties. AB - An approach to the synthesis of moving virtual sound sources with complex radiation properties in wave field synthesis is presented. The approach exploits the fact that any stationary sound source of finite spatial extent radiates spherical waves at sufficient distance. The angular dependency of the radiation properties of the source under consideration is reflected by the amplitude and phase distribution on the spherical wave fronts. The sound field emitted by a uniformly moving monopole source is derived and the far-field radiation properties of the complex virtual source under consideration are incorporated in order to derive a closed-form expression for the loudspeaker driving signal. The results are illustrated via numerical simulations of the synthesis of the sound field of a sample moving complex virtual source. PMID- 22087910 TI - Enhancement of interaural level differences improves sound localization in bimodal hearing. AB - Users of a cochlear implant together with a contralateral hearing aid-so-called bimodal listeners-have difficulties with localizing sound sources. This is mainly due to the distortion of interaural time and level difference cues (ITD and ILD), and limited ITD sensitivity. An algorithm is presented that enhances ILD cues. Horizontal plane sound-source localization performance of six bimodal listeners was evaluated in (1) a real sound field with their clinical devices, (2) in a virtual sound field, under direct computer control, and (3) in a virtual sound field with ILD enhancement. The results in the real sound field did not differ significantly from the results in the virtual field, and ILD enhancement improved localization performance by 4 degrees -10 degrees absolute error, relative to a mean absolute error of 28 degrees in the condition without ILD enhancement. PMID- 22087911 TI - Characterization of the perceived sound of trauma-induced tinnitus in gerbils. AB - Tinnitus often develops following inner ear pathologies, like acoustic trauma. Therefore, an acoustic trauma model of tinnitus in gerbils was established using a modulated acoustic startle response. Cochlear trauma evoked by exposure to narrow-band noise at 10 kHz was assessed by auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE). Threshold shift amounted to about 25 dB at frequencies > 10 kHz. Induction of a phantom-noise perception was documented by an acoustic startle response paradigm. A reduction of the gap prepulse inhibition of acoustic startle (GPIAS) was taken as evidence for tinnitus at the behavioral level. Three to five weeks after trauma the ABR and DPOAE thresholds were back to normal. At that time, a reduction of GPIAS in the frequency range 16-20 kHz indicated a phantom noise perception. Seven weeks post trauma the tinnitus-affected frequency range became narrow and shifted to the center-trauma frequency at 10 kHz. Taken together, by investigating frequency dependent effects in detail, this study in gerbils found trauma-evoked tinnitus developing in the frequency range bordering the low frequency slope of the induced noise trauma. This supports the theory of lateral inhibition as the physiological basis of tinnitus. PMID- 22087912 TI - Behavioral estimates of basilar-membrane compression: additivity of forward masking in noise-masked normal-hearing listeners. AB - Cochlear hearing loss is often associated with a loss of basilar-membrane (BM) compression, which in turn may contribute to degraded processing of suprathreshold stimuli. Behavioral estimates of compression may therefore be useful as long as they are valid over a wide range of levels and frequencies. Additivity of forward masking (AFM) may provide such a measure, but research to date lacks normative data from normal-hearing (NH) listeners at high sound levels, which is necessary to evaluate data from hearing-impaired (HI) listeners. The present study measured AFM in six NH listeners for signal frequencies of 500, 1500, and 4000 Hz in the presence of background noise, designed to elevate signal thresholds to levels similar to those experienced by HI listeners. Results consistent with compressive BM responses were found for all six listeners at 500 Hz, five listeners at 1500 Hz, but only two listeners at 4000 Hz. Further measurements in the absence of background noise also indicated a lack of consistent compression at 4000 Hz at higher signal levels, in contrast to earlier results collected at lower levels. A better understanding of this issue will be required before AFM can be used as a general behavioral estimate of BM compression. PMID- 22087913 TI - A neurocognitive model of recognition and pitch segregation. AB - This paper describes a neurocognitive model of pitch segregation in which it is proposed that recognition mechanisms initiate early in auditory processing pathways so that long-term memory templates may be employed to segregate and integrate auditory features. In this model neural representations of pitch height are primed by the location and pattern of excitation across auditory filter channels in relation to long-term memory templates for common stimuli. Since waveform driven pitch mechanisms may produce information at multiple frequencies for tonal stimuli, pitch priming was assumed to include competitive inhibition that would allow only one pitch estimation at any time. Consequently concurrent pitch information must be relayed to short-term memory via a parallel mechanism that employs pitch information contained in the long-term memory template of the chord. Pure tones, harmonic complexes and two pitch chords of harmonic complexes were correctly classified by the correlation of templates comprising auditory nerve excitation and off-frequency inhibition with the excitation patterns of stimuli. The model then replicated behavioral data for pitch matching of concurrent vowels. Comparison of model outputs to the behavioral data suggests that inability to recognize a stimulus was associated with poor pitch segregation due to the use of inappropriate pitch priming strategies. PMID- 22087914 TI - Voice segregation by difference in fundamental frequency: evidence for harmonic cancellation. AB - Two experiments investigated listeners' ability to use a difference of two semitones in fundamental frequency (F0) to segregate a target voice from harmonic complex tones, with speech-like spectral profiles. Masker partials were in random phase (experiment 1) or in sine phase (experiment 2) and stimuli were presented over headphones. Target's and masker's harmonicity were each distorted by F0 modulation and reverberation. The F0 of each source was manipulated (monotonized or modulated by 2 semitones at 5 Hz) factorially. In addition, all sources were presented from the same location in a virtual room with controlled reverberation, assigned factorially to each source. In both experiments, speech reception thresholds increased by about 2 dB when the F0 of the masker was modulated and increased by about 6 dB when, in addition to F0 modulation, the masker was reverberant. Masker partial phases did not influence the results. The results suggest that F0-segregation relies upon the masker's harmonicity, which is disrupted by rapid modulation. This effect is compounded by reverberation. In addition, F0-segregation was found to be independent of the depth of masker envelope modulations. PMID- 22087915 TI - Effects of the selective disruption of within- and across-channel cues to comodulation masking release. AB - In many experiments on comodulation masking release (CMR), both across- and within-channel cues may be available. This makes it difficult to determine the mechanisms underlying CMR. The present study compared CMR in a flanking-band (FB) paradigm for a situation in which only across-channel cues were likely to be available [FBs placed distally from the on-frequency band (OFB)] and a situation where both across- and within-channel cues might have been available (proximally spaced FBs, for which larger CMRs have previously been observed). The use of across-channel cues was selectively disrupted using a manipulation of auditory grouping factors, following Dau et al. [J. Acoust. Soc. Am. 125, 2182-2188(2009)] and the use of within-channel cues was selectively disrupted using a manipulation called "OFB reversal," following Goldman et al. [J. Acoust. Soc. Am. 129, 3181 3193 (2011)]. The auditory grouping manipulation eliminated CMR for the distal-FB configuration and reduced CMR for the proximal-FB configuration. This may indicate that across-channel cues are available for proximal FB placement. CMR for the proximal-FB configuration persisted when both manipulations were used together, which suggests that OFB reversal does not entirely eliminate within channel cues. PMID- 22087916 TI - The importance for speech intelligibility of random fluctuations in "steady" background noise. AB - Spectrally shaped steady noise is commonly used as a masker of speech. The effects of inherent random fluctuations in amplitude of such a noise are typically ignored. Here, the importance of these random fluctuations was assessed by comparing two cases. For one, speech was mixed with steady speech-shaped noise and N-channel tone vocoded, a process referred to as signal-domain mixing (SDM); this preserved the random fluctuations of the noise. For the second, the envelope of speech alone was extracted for each vocoder channel and a constant was added corresponding to the root-mean-square value of the noise envelope for that channel. This is referred to as envelope-domain mixing (EDM); it removed the random fluctuations of the noise. Sinusoidally modulated noise and a single talker were also used as backgrounds, with both SDM and EDM. Speech intelligibility was measured for N = 12, 19, and 30, with the target-to background ratio fixed at -7 dB. For SDM, performance was best for the speech background and worst for the steady noise. For EDM, this pattern was reversed. Intelligibility with steady noise was consistently very poor for SDM, but near ceiling for EDM, demonstrating that the random fluctuations in steady noise have a large effect. PMID- 22087917 TI - Discrimination of the spectral density of multitone complexes. AB - Spectral density (D), defined as the number of partials comprising a sound divided by its bandwidth, has been suggested as cue for the identification of the size and shape of sound sources. Few data are available, however, on the ability of listeners to discriminate differences in spectral density. In a cue comparison, forced-choice procedure with feedback, three highly practiced listeners discriminated differences in the spectral density of multitone complexes varying in bandwidth (W = 500-1500 Hz), center frequency (f(c) = 500 2000 Hz), and number of tones (N = 6-31). To reduce extraneous cues for discrimination, the overall level of the complexes was roved, and the frequencies were drawn at random uniformly over a fixed bandwidth and center frequency for each presentation. Psychometric functions were obtained relating percent correct discrimination to DeltaD in each condition. For D < 0.02 Hz(-1), the steepness of the functions remained constant across conditions, but for D > 0.02 Hz(-1), they increased with D. The increase, moreover, was accompanied by a reduction in the upper asymptote of the functions. The data were well fit by a model in which spectral density discrimination is determined by the frequency separation of components on an equivalent rectangular bandwidth scale, yielding a roughly constant Weber fraction of DeltaD/D = 0.3. PMID- 22087918 TI - The effect of hearing loss on the resolution of partials and fundamental frequency discrimination. AB - The relationship between the ability to hear out partials in complex tones, discrimination of the fundamental frequency (F0) of complex tones, and frequency selectivity was examined for subjects with mild-to-moderate cochlear hearing loss. The ability to hear out partials was measured using a two-interval task. Each interval included a sinusoid followed by a complex tone; one complex contained a partial with the same frequency as the sinusoid, whereas in the other complex that partial was missing. Subjects had to indicate the interval in which the partial was present in the complex. The components in the complex were uniformly spaced on the ERB(N)-number scale. Performance was generally good for the two "edge" partials, but poorer for the inner partials. Performance for the latter improved with increasing spacing. F0 discrimination was measured for a bandpass-filtered complex tone containing low harmonics. The equivalent rectangular bandwidth (ERB) of the auditory filter was estimated using the notched-noise method for center frequencies of 0.5, 1, and 2 kHz. Significant correlations were found between the ability to hear out inner partials, F0 discrimination, and the ERB. The results support the idea that F0 discrimination of tones with low harmonics depends on the ability to resolve the harmonics. PMID- 22087919 TI - The Timbre Toolbox: extracting audio descriptors from musical signals. AB - The analysis of musical signals to extract audio descriptors that can potentially characterize their timbre has been disparate and often too focused on a particular small set of sounds. The Timbre Toolbox provides a comprehensive set of descriptors that can be useful in perceptual research, as well as in music information retrieval and machine-learning approaches to content-based retrieval in large sound databases. Sound events are first analyzed in terms of various input representations (short-term Fourier transform, harmonic sinusoidal components, an auditory model based on the equivalent rectangular bandwidth concept, the energy envelope). A large number of audio descriptors are then derived from each of these representations to capture temporal, spectral, spectrotemporal, and energetic properties of the sound events. Some descriptors are global, providing a single value for the whole sound event, whereas others are time-varying. Robust descriptive statistics are used to characterize the time varying descriptors. To examine the information redundancy across audio descriptors, correlational analysis followed by hierarchical clustering is performed. This analysis suggests ten classes of relatively independent audio descriptors, showing that the Timbre Toolbox is a multidimensional instrument for the measurement of the acoustical structure of complex sound signals. PMID- 22087920 TI - Effects of inducer continuity on auditory stream segregation: comparison of physical and perceived continuity in different contexts. AB - The factors influencing the stream segregation of discrete tones and the perceived continuity of discrete tones as continuing through an interrupting masker are well understood as separate phenomena. Two experiments tested whether perceived continuity can influence the build-up of stream segregation by manipulating the perception of continuity during an induction sequence and measuring streaming in a subsequent test sequence comprising three triplets of low and high frequency tones (LHL-[ellipsis (horizontal)]). For experiment 1, a 1.2-s standard induction sequence comprising six 100-ms L-tones strongly promoted segregation, whereas a single extended L-inducer (1.1 s plus 100-ms silence) did not. Segregation was similar to that following the single extended inducer when perceived continuity was evoked by inserting noise bursts between the individual tones. Reported segregation increased when the noise level was reduced such that perceived continuity no longer occurred. Experiment 2 presented a 1.3-s continuous inducer created by bridging the 100-ms silence between an extended L inducer and the first test-sequence tone. This configuration strongly promoted segregation. Segregation was also increased by filling the silence after the extended inducer with noise, such that it was perceived like a bridging inducer. Like physical continuity, perceived continuity can promote or reduce test sequence streaming, depending on stimulus context. PMID- 22087922 TI - Binaural interference in bilateral cochlear-implant listeners. AB - This work was aimed at determining whether binaural interference occurs in electric hearing, and if so, whether it occurs as a consequence of perceptual grouping (central explanation) or if it is related to the spread of excitation in the cochlea (peripheral explanation). Six bilateral cochlear-implant listeners completed a series of experiments in which they judged the lateral position of a target pulse train, lateralized via interaural time or level differences, in the presence of an interfering diotic pulse train. The target and interferer were presented at widely separated electrode pairs (one basal and one apical). The results are broadly similar to those reported for acoustic hearing. All listeners but one showed significant binaural interference in at least one of the stimulus conditions. In all cases of interference, a robust recovery was observed when the interferer was presented as part of an ongoing stream of identical pulse trains, suggesting that the interference was at least partly centrally mediated. Overall, the results suggest that both simultaneous and sequential grouping mechanisms operate in electric hearing, at least for stimuli with a wide tonotopic separation. PMID- 22087921 TI - Level-dependent changes in detection of temporal gaps in noise markers by adults with normal and impaired hearing. AB - Compression in the basilar-membrane input-output response flattens the temporal envelope of a fluctuating signal when more gain is applied to lower level than higher level temporal components. As a result, level-dependent changes in gap detection for signals with different depths of envelope fluctuation and for subjects with normal and impaired hearing may reveal effects of compression. To test these assumptions, gap detection with and without a broadband noise was measured with 1, 000-Hz-wide (flatter) and 50-Hz-wide (fluctuating) noise markers as a function of marker level. As marker level increased, background level also increased, maintaining a fixed acoustic signal-to-noise ratio (SNR) to minimize sensation-level effects on gap detection. Significant level-dependent changes in gap detection were observed, consistent with effects of cochlear compression. For the flatter marker, gap detection that declines with increases in level up to mid levels and improves with further increases in level may be explained by an effective flattening of the temporal envelope at mid levels, where compression effects are expected to be strongest. A flatter effective temporal envelope corresponds to a reduced effective SNR. The effects of a reduction in compression (resulting in larger effective SNRs) may contribute to better-than-normal gap detection observed for some hearing-impaired listeners. PMID- 22087923 TI - Combined spectral and temporal enhancement to improve cochlear-implant speech perception. AB - The present study examined the effect of combined spectral and temporal enhancement on speech recognition by cochlear-implant (CI) users in quiet and in noise. The spectral enhancement was achieved by expanding the short-term Fourier amplitudes in the input signal. Additionally, a variation of the Transient Emphasis Spectral Maxima (TESM) strategy was applied to enhance the short duration consonant cues that are otherwise suppressed when processed with spectral expansion. Nine CI users were tested on phoneme recognition tasks and ten CI users were tested on sentence recognition tasks both in quiet and in steady, speech-spectrum-shaped noise. Vowel and consonant recognition in noise were significantly improved with spectral expansion combined with TESM. Sentence recognition improved with both spectral expansion and spectral expansion combined with TESM. The amount of improvement varied with individual CI users. Overall the present results suggest that customized processing is needed to optimize performance according to not only individual users but also listening conditions. PMID- 22087924 TI - Phonation threshold pressure and onset frequency in a two-layer physical model of the vocal folds. AB - The influence of vocal fold geometry and stiffness on phonation onset was experimentally investigated using a body-cover physical model of the vocal folds. Results showed that a lower phonation threshold pressure and phonation onset frequency can be achieved by reducing body-layer or cover-layer stiffness, reducing medial surface thickness, or increasing cover-layer depth. Increasing body-layer stiffness also restricted vocal fold motion to the cover layer and reduced prephonatory glottal opening. Excitation of anterior-posterior modes was also observed, particularly for large values of the body-cover stiffness ratio. The results of this study were also discussed in relation to previous theoretical and experimental studies. PMID- 22087925 TI - Segmentation of expiratory and inspiratory sounds in baby cry audio recordings using hidden Markov models. AB - The paper describes an application of machine learning techniques to identify expiratory and inspiration phases from the audio recording of human baby cries. Crying episodes were recorded from 14 infants, spanning four vocalization contexts in their first 12 months of age; recordings from three individuals were annotated manually to identify expiratory and inspiratory sounds and used as training examples to segment automatically the recordings of the other 11 individuals. The proposed algorithm uses a hidden Markov model architecture, in which state likelihoods are estimated either with Gaussian mixture models or by converting the classification decisions of a support vector machine. The algorithm yields up to 95% classification precision (86% average), and its ability generalizes over different babies, different ages, and vocalization contexts. The technique offers an opportunity to quantify expiration duration, count the crying rate, and other time-related characteristics of baby crying for screening, diagnosis, and research purposes over large populations of infants. PMID- 22087926 TI - A cross-language study of compensation in response to real-time formant perturbation. AB - Past studies have shown that when formants are perturbed in real time, speakers spontaneously compensate for the perturbation by changing their formant frequencies in the opposite direction to the perturbation. Further, the pattern of these results suggests that the processing of auditory feedback error operates at a purely acoustic level. This hypothesis was tested by comparing the response of three language groups to real-time formant perturbations, (1) native English speakers producing an English vowel /epsilon/, (2) native Japanese speakers producing a Japanese vowel (/e([inverted perpendicular])/), and (3) native Japanese speakers learning English, producing /epsilon/. All three groups showed similar production patterns when F1 was decreased; however, when F1 was increased, the Japanese groups did not compensate as much as the native English speakers. Due to this asymmetry, the hypothesis that the compensatory production for formant perturbation operates at a purely acoustic level was rejected. Rather, some level of phonological processing influences the feedback processing behavior. PMID- 22087927 TI - The interpretation of speech reception threshold data in normal-hearing and hearing-impaired listeners: steady-state noise. AB - Speech-in-noise-measurements are important in clinical practice and have been the subject of research for a long time. The results of these measurements are often described in terms of the speech reception threshold (SRT) and SNR loss. Using the basic concepts that underlie several models of speech recognition in steady state noise, the present study shows that these measures are ill-defined, most importantly because the slope of the speech recognition functions for hearing impaired listeners always decreases with hearing loss. This slope can be determined from the slope of the normal-hearing speech recognition function when the SRT for the hearing-impaired listener is known. The SII-function (i.e., the speech intelligibility index (SII) against SNR) is important and provides insights into many potential pitfalls when interpreting SRT data. Standardized SNR loss, sSNR loss, is introduced as a universal measure of hearing loss for speech in steady-state noise. Experimental data demonstrates that, unlike the SRT or SNR loss, sSNR loss is invariant to the target point chosen, the scoring method or the type of speech material. PMID- 22087928 TI - Prediction of the influence of reverberation on binaural speech intelligibility in noise and in quiet. AB - Reverberation usually degrades speech intelligibility for spatially separated speech and noise sources since spatial unmasking is reduced and late reflections decrease the fidelity of the received speech signal. The latter effect could not satisfactorily be predicted by a recently presented binaural speech intelligibility model [Beutelmann et al. (2010). J. Acoust. Soc. Am. 127, 2479 2497]. This study therefore evaluated three extensions of the model to improve its predictions: (1) an extension of the speech intelligibility index based on modulation transfer functions, (2) a correction factor based on the room acoustical quantity "definition," and (3) a separation of the speech signal into useful and detrimental parts. The predictions were compared to results of two experiments in which speech reception thresholds were measured in a reverberant room in quiet and in the presence of a noise source for listeners with normal hearing. All extensions yielded better predictions than the original model when the influence of reverberation was strong, while predictions were similar for conditions with less reverberation. Although model (3) differed substantially in the assumed interaction of binaural processing and early reflections, its predictions were very similar to model (2) that achieved the best fit to the data. PMID- 22087929 TI - An evaluation of objective measures for intelligibility prediction of time frequency weighted noisy speech. AB - Existing objective speech-intelligibility measures are suitable for several types of degradation, however, it turns out that they are less appropriate in cases where noisy speech is processed by a time-frequency weighting. To this end, an extensive evaluation is presented of objective measure for intelligibility prediction of noisy speech processed with a technique called ideal time frequency (TF) segregation. In total 17 measures are evaluated, including four advanced speech-intelligibility measures (CSII, CSTI, NSEC, DAU), the advanced speech quality measure (PESQ), and several frame-based measures (e.g., SSNR). Furthermore, several additional measures are proposed. The study comprised a total number of 168 different TF-weightings, including unprocessed noisy speech. Out of all measures, the proposed frame-based measure MCC gave the best results (rho = 0.93). An additional experiment shows that the good performing measures in this study also show high correlation with the intelligibility of single-channel noise reduced speech. PMID- 22087931 TI - Linking multiple relaxation, power-law attenuation, and fractional wave equations. AB - The acoustic wave attenuation is described by an experimentally established frequency power law in a variety of complex media, e.g., biological tissue, polymers, rocks, and rubber. Recent papers present a variety of acoustical fractional derivative wave equations that have the ability to model power-law attenuation. On the other hand, a multiple relaxation model is widely recognized as a physically based description of the acoustic loss mechanisms as developed by Nachman et al. [J. Acoust. Soc. Am. 88, 1584-1595 (1990)]. Through assumption of a continuum of relaxation mechanisms, each with an effective compressibility described by a distribution related to the Mittag-Leffler function, this paper shows that the wave equation corresponding to the multiple relaxation approach is identical to a given fractional derivative wave equation. This work therefore provides a physically based motivation for use of fractional wave equations in acoustic modeling. PMID- 22087930 TI - The effects of selective consonant amplification on sentence recognition in noise by hearing-impaired listeners. AB - Weak consonants (e.g., stops) are more susceptible to noise than vowels, owing partially to their lower intensity. This raises the question whether hearing impaired (HI) listeners are able to perceive (and utilize effectively) the high frequency cues present in consonants. To answer this question, HI listeners were presented with clean (noise absent) weak consonants in otherwise noise-corrupted sentences. Results indicated that HI listeners received significant benefit in intelligibility (4 dB decrease in speech reception threshold) when they had access to clean consonant information. At extremely low signal-to-noise ratio (SNR) levels, however, HI listeners received only 64% of the benefit obtained by normal-hearing listeners. This lack of equitable benefit was investigated in Experiment 2 by testing the hypothesis that the high-frequency cues present in consonants were not audible to HI listeners. This was tested by selectively amplifying the noisy consonants while leaving the noisy sonorant sounds (e.g., vowels) unaltered. Listening tests indicated small (~10%), but statistically significant, improvements in intelligibility at low SNR conditions when the consonants were amplified in the high-frequency region. Selective consonant amplification provided reliable low-frequency acoustic landmarks that in turn facilitated a better lexical segmentation of the speech stream and contributed to the small improvement in intelligibility. PMID- 22087932 TI - Quantifying seismic survey reverberation off the Alaskan North Slope. AB - Shallow-water airgun survey activities off the North Slope of Alaska generate impulsive sounds that are the focus of much regulatory attention. Reverberation from repetitive airgun shots, however, can also increase background noise levels, which can decrease the detection range of nearby passive acoustic monitoring (PAM) systems. Typical acoustic metrics for impulsive signals provide no quantitative information about reverberation or its relative effect on the ambient acoustic environment. Here, two conservative metrics are defined for quantifying reverberation: a minimum level metric measures reverberation levels that exist between airgun pulse arrivals, while a reverberation metric estimates the relative magnitude of reverberation vs expected ambient levels in the hypothetical absence of airgun activity, using satellite-measured wind data. The metrics are applied to acoustic data measured by autonomous recorders in the Alaskan Beaufort Sea in 2008 and demonstrate how seismic surveys can increase the background noise over natural ambient levels by 30-45 dB within 1 km of the activity, by 10-25 dB within 15 km of the activity, and by a few dB at 128 km range. These results suggest that shallow-water reverberation would reduce the performance of nearby PAM systems when monitoring for marine mammals within a few kilometers of shallow-water seismic surveys. PMID- 22087933 TI - The mechanism of interaction between focused ultrasound and microbubbles in blood brain barrier opening in mice. AB - The activation of bubbles by an acoustic field has been shown to temporarily open the blood-brain barrier (BBB), but the trigger cause responsible for the physiological effects involved in the process of BBB opening remains unknown. Here, the trigger cause (i.e., physical mechanism) of the focused ultrasound induced BBB opening with monodispersed microbubbles is identified. Sixty-seven mice were injected intravenously with bubbles of 1-2, 4-5, or 6-8 MUm in diameter and the concentration of 10(7) numbers/ml. The right hippocampus of each mouse was then sonicated using focused ultrasound (1.5 MHz frequency, 100 cycles pulse length, 10 Hz pulse repetition frequency, 1 min duration). Peak-rarefactional pressures of 0.15, 0.30, 0.45, or 0.60 MPa were applied to identify the threshold of BBB opening and inertial cavitation (IC). Our results suggest that the BBB opens with nonlinear bubble oscillation when the bubble diameter is similar to the capillary diameter and with inertial cavitation when it is not. The bubble may thus have to be in contact with the capillary wall to induce BBB opening without IC. BBB opening was shown capable of being induced safely with nonlinear bubble oscillation at the pressure threshold and its volume was highly dependent on both the acoustic pressure and bubble diameter. PMID- 22087934 TI - Low frequency narrow-band calls in bottlenose dolphins (Tursiops truncatus): signal properties, function, and conservation implications. AB - Dolphins routinely use sound for social purposes, foraging and navigating. These sounds are most commonly classified as whistles (tonal, frequency modulated, typical frequencies 5-10 kHz) or clicks (impulsed and mostly ultrasonic). However, some low frequency sounds have been documented in several species of dolphins. Low frequency sounds produced by bottlenose dolphins (Tursiops truncatus) were recorded in three locations along the Gulf of Mexico. Sounds were characterized as being tonal with low peak frequencies (mean = 990 Hz), short duration (mean = 0.069 s), highly harmonic, and being produced in trains. Sound duration, peak frequency and number of sounds in trains were not significantly different between Mississippi and the two West Florida sites, however, the time interval between sounds within trains in West Florida was significantly shorter than in Mississippi (t = -3.001, p = 0.011). The sounds were significantly correlated with groups engaging in social activity (F=8.323, p=0.005). The peak frequencies of these sounds were below what is normally thought of as the range of good hearing in bottlenose dolphins, and are likely subject to masking by boat noise. PMID- 22087935 TI - Characteristics of biosonar signals from the northern bottlenose whale, Hyperoodon ampullatus. AB - The biosonar pulses from free-ranging northern bottlenose whales (Hyperoodon ampullatus) were recorded with a linear hydrophone array. Signals fulfilling criteria for being recorded close to the acoustic axis of the animal (a total of 10 clicks) had a frequency upsweep from 20 to 55 kHz and durations of 207 to 377 MUs (measured as the time interval containing 95% of the signal energy). The source level of these signals, denoted pulses, was 175-202 dB re 1 MUPa rms at 1 m. The pulses had a directionality index of at least 18 dB. Interpulse intervals ranged from 73 to 949 ms (N = 856). Signals of higher repetition rates had interclick intervals of 5.8-13.1 ms (two sequences, made up of 59 and 410 clicks, respectively). These signals, denoted clicks, had a shorter duration (43-200 MUs) and did not have the frequency upsweep characterizing the pulses of low repetition rates. The data show that the northern bottlenose whale emits signals similar to three other species of beaked whale. These signals are distinct from the three other types of biosonar signals of toothed whales. It remains unclear why the signals show this grouping, and what consequences it has on echolocation performance. PMID- 22087936 TI - Similarities in echolocation strategy and click characteristics between a Pseudorca crassidens and a Tursiops truncatus. AB - A previous comparative analysis of normalized click amplitude spectra from a Tursiops truncatus has shown that those frequencies with the lowest click-to click variability in spectral content were the frequencies the animal paid attention to during target discrimination tasks. In that case, the dolphin only paid attention to the frequency range between 29-42 kHz which had a significantly higher degree of consistency in spectral content than frequencies above 42 kHz. Here it is shown that despite their morphological and behavioral differences, this same pattern of consistency was used by a Pseudorca crassidens performing a similar discrimination task. This comparison between species provides a foundation for using spectral level variability to determine the frequencies most important for echolocation in rare species and non-captive animals. Such results provide key information for successful management. PMID- 22087937 TI - Source level reduction and sonar beam aiming in landing big brown bats (Eptesicus fuscus). AB - Reduction of echolocation call source levels in bats has previously been studied using set-ups with one microphone. By using a 16 microphone array, sound pressure level (SPL) variations, possibly caused by the scanning movements of the bat, can be excluded and the sonar beam aiming can be studied. During the last two meters of approach flights to a landing platform in a large flight room, five big brown bats aimed sonar beams at the landing site and reduced the source level on average by 7 dB per halving of distance. Considerable variation was found among the five individuals in the amount of source level reduction ranging from 4 to 9 dB per halving of distance. These results are discussed with respect to automatic gain control and intensity compensation and the combination of the two effects. It is argued that the two effects together do not lead to a stable echo level at the cochlea. This excludes a tightly coupled closed loop feed back control system as an explanation for the observed reduction of signal SPL in landing big brown bats. PMID- 22087938 TI - Effects of noise levels and call types on the source levels of killer whale calls. AB - Accurate parameter estimates relevant to the vocal behavior of marine mammals are needed to assess potential effects of anthropogenic sound exposure including how masking noise reduces the active space of sounds used for communication. Information about how these animals modify their vocal behavior in response to noise exposure is also needed for such assessment. Prior studies have reported variations in the source levels of killer whale sounds, and a more recent study reported that killer whales compensate for vessel masking noise by increasing their call amplitude. The objectives of the current study were to investigate the source levels of a variety of call types in southern resident killer whales while also considering background noise level as a likely factor related to call source level variability. The source levels of 763 discrete calls along with corresponding background noise were measured over three summer field seasons in the waters surrounding the San Juan Islands, WA. Both noise level and call type were significant factors on call source levels (1-40 kHz band, range of 135.0 175.7 dB(rms) re 1 [micro sign]Pa at 1 m). These factors should be considered in models that predict how anthropogenic masking noise reduces vocal communication space in marine mammals. PMID- 22087939 TI - A re-evaluation of auditory filter shape in delphinid odontocetes: evidence of constant-bandwidth filters. AB - The auditory filter shape of delphinid odontocetes was previously considered to be typically mammalian constant-quality in which filter bandwidths increase proportionally with frequency. Recent studies with porpoises demonstrate constant bandwidth portions of the auditory filter. The critical ratios for a bottlenose dolphin were measured between 40 and 120 kHz by behaviorally determining the subject's ability to detect pure tones in the presence of white noise. Critical ratios as a function of frequency were constant, indicating the auditory filter acts as a constant-bandwidth system in this frequency range. Re-analysis of past studies supports these findings, and suggests the delphinid auditory system is best characterized as a constant-Q system below 40 kHz and a constant-bandwidth like system between 40 kHz and 120 kHz before returning to a constant Q pattern at the highest frequencies. PMID- 22087940 TI - Effects of auditory recognition learning on the perception of vocal features in European starlings (Sturnus vulgaris). AB - Learning to recognize complex sensory signals can change the way they are perceived. European starlings (Sturnus vulgaris) recognize other starlings by their song, which consists of a series of complex, stereotyped motifs. Song recognition learning is accompanied by plasticity in secondary auditory areas, suggesting that perceptual learning is involved. Here, to investigate whether perceptual learning can be observed behaviorally, a same-different operant task was used to measure how starlings perceived small differences in motif structure. Birds trained to recognize conspecific songs were better at detecting variations in motifs from the songs they learned, even though this variation was not directly necessary to learn the associative task. Discrimination also improved as the reference stimulus was repeated multiple times. Perception of the much larger differences between different motifs was unaffected by training. These results indicate that sensory representations of motifs are enhanced when starlings learn to recognize songs. PMID- 22087941 TI - Subjective loudness level measurements and equal loudness contours in a bottlenose dolphin (Tursiops truncatus). AB - Loudness level measurements in human listeners are straightforward; however, it is difficult to convey the concepts of loudness matching or loudness comparison to (non-human) animals. For this reason, prior studies have relied upon objective measurements, such as response latency, to estimate equal loudness contours in animals. In this study, a bottlenose dolphin was trained to perform a loudness comparison test, where the listener indicates which of two sequential tones is louder. To enable reward of the dolphin, most trials featured tones with identical or similar frequencies, but relatively large sound pressure level differences, so that the loudness relationship was known. A relatively small percentage of trials were "probe" trials, with tone pairs whose loudness relationship was not known. Responses to the probe trials were used to construct psychometric functions describing the loudness relationship between a tone at a particular frequency and sound pressure level and that of a reference tone at 10 kHz with a sound pressure level of 90, 105, or 115 dB re 1 MUPa. The loudness relationships were then used to construct equal loudness contours and auditory weighting functions that can be used to predict the frequency-dependent effects of noise on odontocetes. PMID- 22087942 TI - Excitation threshold for subharmonic generation from contrast microbubbles. AB - Six models of contrast microbubbles are investigated to determine the excitation threshold for subharmonic generation. The models are applied to a commercial contrast agent; its characteristic parameters according to each model are determined using experimentally measured ultrasound attenuation. In contrast to the classical perturbative result, the minimum threshold for subharmonic generation is not always predicted at excitation with twice the resonance frequency; instead it occurs over a range of frequencies from resonance to twice the resonance frequency. The quantitative variation of the threshold with frequency depends on the model and the bubble radius. All models are transformed into a common interfacial rheological form, where the encapsulation is represented by two radius dependent surface properties-effective surface tension and surface dilatational viscosity. Variation of the effective surface tension with radius, specifically having an upper limit (resulting from strain softening or rupture of the encapsulation during expansion), plays a critical role. Without the upper limit, the predicted threshold is extremely large, especially near the resonance frequency. Having a lower limit on surface tension (e.g., zero surface tension in the buckled state) increases the threshold value at twice the resonance frequency, in some cases shifting the minimum threshold toward resonance. PMID- 22087943 TI - Comparison of fundamental, second harmonic, and superharmonic imaging: a simulation study. AB - In medical ultrasound, fundamental imaging (FI) uses the reflected echoes from the same spectral band as that of the emitted pulse. The transmission frequency determines the trade-off between penetration depth and spatial resolution. Tissue harmonic imaging (THI) employs the second harmonic of the emitted frequency band to construct images. Recently, superharmonic imaging (SHI) has been introduced, which uses the third to the fifth (super) harmonics. The harmonic level is determined by two competing phenomena: nonlinear propagation and frequency dependent attenuation. Thus, the transmission frequency yielding the optimal trade-off between the spatial resolution and the penetration depth differs for THI and SHI. This paper quantitatively compares the concepts of fundamental, second harmonic, and superharmonic echocardiography at their optimal transmission frequencies. Forward propagation is modeled using a 3D-KZK implementation and the iterative nonlinear contrast source (INCS) method. Backpropagation is assumed to be linear. Results show that the fundamental lateral beamwidth is the narrowest at focus, while the superharmonic one is narrower outside the focus. The lateral superharmonic roll-off exceeds the fundamental and second harmonic roll-off. Also, the axial resolution of SHI exceeds that of FI and THI. The far-field pulse echo superharmonic pressure is lower than that of the fundamental and second harmonic. SHI appears suited for echocardiography and is expected to improve its image quality at the cost of a slight reduction in depth-of-field. PMID- 22087991 TI - Bubbles. Foreword. PMID- 22087992 TI - Review of scattering and extinction cross-sections, damping factors, and resonance frequencies of a spherical gas bubble. AB - Perhaps the most familiar concepts when discussing acoustic scattering by bubbles are the resonance frequency for bubble pulsation, the bubbles' damping, and their scattering and extinction cross-sections, all of which are used routinely in oceanography, sonochemistry, and biomedicine. The apparent simplicity of these concepts is illusory: there exist multiple, sometimes contradictory definitions for their components. This paper reviews expressions and definitions in the literature for acoustical cross-sections, resonance frequencies, and damping factors of a spherically pulsating gas bubble in an infinite liquid medium, deriving two expressions for "resonance frequency" that are compared and reconciled with two others from the reviewed literature. In order to prevent errors, care is needed by researchers when combining results from different publications that might have used internally correct but mutually inconsistent definitions. Expressions are presented for acoustical cross-sections associated with forced pulsations damped by liquid shear and (oft-neglected) bulk or dilatational viscosities, gas thermal diffusivity, and acoustic re-radiation. The concept of a dimensionless "damping coefficient" is unsuitable for radiation damping because different cross-sections would require different functional forms for this parameter. Instead, terms based on the ratio of bubble radius to acoustic wavelength are included explicitly in the cross-sections where needed. PMID- 22087993 TI - The acoustic emissions of cavitation bubbles in stretched vortices. AB - Pairs of unequal strength, counter-rotating vortices were produced in order to examine the inception, dynamics, and acoustic emission of cavitation bubbles in rapidly stretching vortices. The acoustic signatures of these cavitation bubbles were characterized during their inception, growth, and collapse. Growing and collapsing bubbles often produced a sharp, broadband, pop sound. The spectrum of these bubbles, and the peak resonant frequency can generally be related to quiescent flow bubble dynamics and corresponding resonant frequencies. However, some elongated cavitation bubbles produced a short tonal burst, or chirp, with frequencies on the order of a few kilohertz. Theses frequencies are too low to be related to resonant frequencies of a bubble in a quiescent flow. Instead, the frequency content of the acoustic signal during bubble inception and growth is related to the volumetric oscillations of the bubble while it interacted with vortical flow that surrounds the bubble (i.e., the resonant frequency of the vortex-bubble system). A relationship was determined between the observed peak frequency of the oscillations, the highly stretched vortex properties, and the water nuclei content. It was found that different cavitation spectra could relate to different flow and fluid properties and therefore would not scale in the same manner. PMID- 22087994 TI - Regimes of bubble volume oscillations in a pipe. AB - The effect of an acoustically driven bubble on the acoustics of a liquid-filled pipe is theoretically analyzed and the dimensionless groups of the problem are identified. The different regimes of bubble volume oscillations are predicted theoretically with these dimensionless groups. Three main regimes can be identified: (1) For small bubbles and weak driving, the effect of the bubble oscillations on the acoustic field can be neglected. (2) For larger bubbles and still small driving, the bubble affects the acoustic field, but due to the small driving, a linear theory is sufficient. (3) For large bubbles and large driving, the two-way coupling between the bubble and the flow dynamics requires the solution of the full nonlinear problem. The developed theory is then applied to an air bubble in a channel of an inkjet printhead. A numerical model is developed to test the predictions of the theoretical analysis. The Rayleigh-Plesset equation is extended to include the influence of the bubble volume oscillations on the acoustic field and vice versa. This modified Rayleigh-Plesset equation is coupled to a channel acoustics calculation and a Navier-Stokes solver for the flow in the nozzle. The numerical simulations indeed confirm the predictions of the theoretical analysis. PMID- 22087995 TI - Effect of static pressure on acoustic energy radiated by cavitation bubbles in viscous liquids under ultrasound. AB - The effect of static pressure on acoustic emissions including shock-wave emissions from cavitation bubbles in viscous liquids under ultrasound has been studied by numerical simulations in order to investigate the effect of static pressure on dispersion of nano-particles in liquids by ultrasound. The results of the numerical simulations for bubbles of 5 MUm in equilibrium radius at 20 kHz have indicated that the optimal static pressure which maximizes the energy of acoustic waves radiated by a bubble per acoustic cycle increases as the acoustic pressure amplitude increases or the viscosity of the solution decreases. It qualitatively agrees with the experimental results by Sauter et al. [Ultrason. Sonochem. 15, 517 (2008)]. In liquids with relatively high viscosity (~200 mPa s), a bubble collapses more violently than in pure water when the acoustic pressure amplitude is relatively large (~20 bar). In a mixture of bubbles of different equilibrium radius (3 and 5 MUm), the acoustic energy radiated by a 5 MUm bubble is much larger than that by a 3 MUm bubble due to the interaction with bubbles of different equilibrium radius. The acoustic energy radiated by a 5 MUm bubble is substantially increased by the interaction with 3 MUm bubbles. PMID- 22087996 TI - Validation of an approximate model for the thermal behavior in acoustically driven bubbles. AB - The chemical production of radicals inside acoustically driven bubbles is determined by the local temperature inside the bubbles. Therefore, modeling of chemical reaction rates in bubbles requires an accurate evaluation of the temperature field and the heat exchange with the liquid. The aim of the present work is to compare a detailed partial differential equation model in which the temperature field is spatially resolved with an ordinary differential equation model in which the bubble contents are assumed to have a uniform average temperature and the heat exchanges are modeled by means of a boundary layer approximation. The two models show good agreement in the range of pressure amplitudes in which the bubble is spherically stable. PMID- 22087997 TI - Modeling cavitation nucleation from laser-illuminated nanoparticles subjected to acoustic stress. AB - In an earlier work by Farny et al. [ARLO 6, 138-143 (2005).] it was demonstrated that the acoustic cavitation threshold in a tissue mimicking gel phantom can be lowered from 4.5 to ~1 MPa by "seeding" the optically transparent phantom with light absorptive gold nanoparticles and irradiating these absorbers with nanosecond pulses of laser light at intensities less than 10 mJ/cm(2). As a follow-up study, a three-stage numerical model was developed to account for prenucleation heating, the nucleation and formation of the vapor cavity, and the resulting vapor bubble dynamics. Through examination of the radius-time evolution of the cavity, the combined thresholds for laser radiant exposure and acoustic peak pressure required to induce inertial cavitation are deduced. It is found that the threshold pressure decreases when laser exposure increases; but the rate depends on exposure levels and the size of the particle. Investigations of the roles of particle size and laser pulse length are performed and optimum choices for these parameters determined in order to obtain inertial cavitation at the lowest possible acoustic pressure and laser intensity. PMID- 22087998 TI - A fractional Fourier transform analysis of a bubble excited by an ultrasonic chirp. AB - The fractional Fourier transform is proposed here as a model based, signal processing technique for determining the size of a bubble in a fluid. The bubble is insonified with an ultrasonic chirp and the radiated pressure field is recorded. This experimental bubble response is then compared with a series of theoretical model responses to identify the most accurate match between experiment and theory which allows the correct bubble size to be identified. The fractional Fourier transform is used to produce a more detailed description of each response, and two-dimensional cross correlation is then employed to identify the similarities between the experimental response and each theoretical response. In this paper the experimental bubble response is simulated by adding various levels of noise to the theoretical model output. The method is compared to the standard technique of using time-domain cross correlation. The proposed method is shown to be far more robust at correctly sizing the bubble and can cope with much lower signal to noise ratios. PMID- 22087999 TI - Combined optical and acoustical detection of single microbubble dynamics. AB - A detailed understanding of the response of single microbubbles subjected to ultrasound is fundamental to a full understanding of the contrast-enhancing abilities of microbubbles in medical ultrasound imaging, in targeted molecular imaging with ultrasound, and in ultrasound-mediated drug delivery with microbubbles. Here, single microbubbles are isolated and their ultrasound-induced radial dynamics recorded with an ultra-high-speed camera at up to 25 million frames per second. The sound emission is recorded simultaneously with a calibrated single element transducer. It is shown that the sound emission can be predicted directly from the optically recorded radial dynamics, and vice versa, that the nanometer-scale radial dynamics can be predicted from the acoustic response recorded in the far field. PMID- 22088000 TI - Ambient acceleration dependence of single-bubble sonoluminescence. AB - Much of the research performed to study SBSL deals with the influence of external parameters (e.g., the host water temperature, the ambient pressure, the type and amount of dissolved gas in the liquid, to name a few) on the bubble dynamics and light emission. In the current paper, work carried out to study the influence of another external parameter-ambient acceleration-is described. The experiments described here were performed on the NASA KC-135 which provided both periods of reduced gravity (10(-3) g) and increased gravity (1.8 g) by flying repeated parabolic maneuvers. The resulting measurements are compared with the predictions of a numerical model and can be understood in the context of the changing hydrostatic head pressure and buoyant force acting on the bubble. PMID- 22088001 TI - Quantitative observations of cavitation activity in a viscoelastic medium. AB - Quantitative experimental observations of single-bubble cavitation in viscoelastic media that would enable validation of existing models are presently lacking. In the present work, single bubble cavitation is induced in an agar gel using a 1.15 MHz high intensity focused ultrasound transducer, and observed using a focused single-element passive cavitation detection (PCD) transducer. To enable quantitative observations, a full receive calibration is carried out of a spherically focused PCD system by a bistatic scattering substitution technique that uses an embedded spherical scatterer and a hydrophone. Adjusting the simulated pressure received by the PCD by the transfer function on receive and the frequency-dependent attenuation of agar gel enables direct comparison of the measured acoustic emissions with those predicted by numerical modeling of single bubble cavitation using a modified Keller-Miksis approach that accounts for viscoelasticity of the surrounding medium. At an incident peak rarefactional pressure near the cavitation threshold, period multiplying is observed in both experiment and numerical model. By comparing the two sets of results, an estimate of the equilibrium bubble radius in the experimental observations can be made, with potential for extension to material parameter estimation. Use of these estimates yields good agreement between model and experiment. PMID- 22088002 TI - Investigation of noninertial cavitation produced by an ultrasonic horn. AB - This paper reports on noninertial cavitation that occurs beyond the zone close to the horn tip to which the inertial cavitation is confined. The noninertial cavitation is characterized by collating the data from a range of measurements of bubbles trapped on a solid surface in this noninertial zone. Specifically, the electrochemical measurement of mass transfer to an electrode is compared with high-speed video of the bubble oscillation. This gas bubble is shown to be a "noninertial" event by electrochemical surface erosion measurements and "ring down" experiments showing the activity and motion of the bubble as the sound excitation was terminated. These measurements enable characterization of the complex environment produced below an operating ultrasonic horn outside of the region where inertial collapse can be detected. The extent to which solid boundaries in the liquid cause the frequencies and shapes of oscillatory modes on the bubble wall to differ from their free field values is discussed. PMID- 22088003 TI - Measuring and modeling the bubble population produced by an underwater explosion. AB - Underwater explosions have been studied intensively in the United States since 1941 [e.g., R. H. Cole, Underwater Explosions (Princeton University Press, Princeton, NJ, 1945), pp. 3-13]. Research to date has primarily focused on the initial shock and subsequent pressure waves caused by the oscillations of the "gas-globe" resulting from charge detonation. These phenomena have relatively short timescales (typically less than 2 s). However, after the gas-globe rises through the water column and breaks the surface, there remains behind a cloud of bubbles and perhaps debris from the explosion container which has been markedly less studied. A recent experiment measured the spatial and temporal acoustic response of the bubble cloud resulting from a 13.6 kg PBXN-111 charge detonated at 15.2 m (50 ft) depth. A directional projector was used to propagate linear frequency-modulated (5-65 kHz) and 40 kHz tonal pulses through the bubble cloud. Two hydrophone arrays were positioned so as to measure the energy lost in propagating through the bubble cloud. Three methods have been utilized to invert measurements and estimate the bubble population. The bubble population estimates have been used to develop a model for the bubble population resulting from an underwater explosion. PMID- 22088004 TI - Suppressing shape instabilities to discover the Bjerknes force instability (L). AB - For sufficiently strong acoustic forcing in a standing wave field, subresonant size bubbles are predicted to be repelled from the pressure antinode. Single bubble sonoluminescence (SBSL) conditions in water do not allow the observation of this instability. This study investigates the possibility that increasing the viscosity of the host liquid can preferentially suppress shape instabilities of a bubble and allow SBSL experiments to be limited by the Bjerknes force instability. PMID- 22088005 TI - Sound propagation in water containing large tethered spherical encapsulated gas bubbles with resonance frequencies in the 50 Hz to 100 Hz range. AB - The efficacy of large tethered encapsulated gas bubbles for the mitigation of low frequency underwater noise was investigated with an acoustic resonator technique. Tethered latex balloons were used as the bubbles, which had radii of approximately 5 cm. Phase speeds were inferred from the resonances of a water and balloon-filled waveguide approximately 1.8 m in length. The Commander and Prosperetti effective-medium model [J. Acoust. Soc. Am. 85, 732-746 (1989)] quantitatively described the observed dispersion from well below to just below the individual bubble resonance frequency, and it qualitatively predicted the frequency range of high attenuation for void fractions between 2% and 5% for collections of stationary balloons within the waveguide. A finite-element model was used to investigate the sensitivity of the waveguide resonance frequencies, and hence the inferred phase speeds, to changes in individual bubble size and position. The results indicate that large tethered encapsulated bubbles could be used mitigate low frequency underwater noise and that the Commander and Prosperetti model would be useful in the design of such a system. PMID- 22088006 TI - The inertial terms in equations of motion for bubbles in tubular vessels or between plates. AB - Equations resembling the Rayleigh-Plesset and Keller-Miksis equations are frequently used to model bubble dynamics in confined spaces, using the standard inertial term RR+3R([middle dot]) (2)/2, where R is the bubble radius. This practice has been widely assumed to be defensible if the bubble is much smaller than the radius of the confining vessel. This paper questions this assumption, and provides a simple rigid wall model for worst-case quantification of the effect on the inertial term of the specific confinement geometry. The relevance to a range of scenarios (including bubbles confined in microfluidic devices; or contained in test chambers for insonification or imaging; or in blood vessels) is discussed. PMID- 22088007 TI - Dynamics of tandem bubble interaction in a microfluidic channel. AB - The dynamics of tandem bubble interaction in a microfluidic channel (800 * 21 MUm, W * H) have been investigated using high-speed photography, with resultant fluid motion characterized by particle imaging velocimetry. A single or tandem bubble is produced reliably via laser absorption by micron-sized gold dots (6 MUm in diameter with 40 MUm in separation distance) coated on a glass surface of the microfluidic channel. Using two pulsed Nd:YAG lasers at lambda = 1064 nm and ~10 MUJ/pulse, the dynamics of tandem bubble interaction (individual maximum bubble diameter of 50 MUm with a corresponding collapse time of 5.7 MUs) are examined at different phase delays. In close proximity (i.e., interbubble distance = 40 MUm or gamma = 0.8), the tandem bubbles interact strongly with each other, leading to asymmetric deformation of the bubble walls and jet formation, as well as the production of two pairs of vortices in the surrounding fluid rotating in opposite directions. The direction and speed of the jet (up to 95 m/s), as well as the orientation and strength of the vortices can be varied by adjusting the phase delay. PMID- 22088009 TI - Model for the dynamics of two interacting axisymmetric spherical bubbles undergoing small shape oscillations. AB - Interaction between acoustically driven or laser-generated bubbles causes the bubble surfaces to deform. Dynamical equations describing the motion of two translating, nominally spherical bubbles undergoing small shape oscillations in a viscous liquid are derived using Lagrangian mechanics. Deformation of the bubble surfaces is taken into account by including quadrupole and octupole perturbations in the spherical-harmonic expansion of the boundary conditions on the bubbles. Quadratic terms in the quadrupole and octupole amplitudes are retained, and surface tension and shear viscosity are included in a consistent manner. A set of eight coupled second-order ordinary differential equations is obtained. Simulation results, obtained by numerical integration of the model equations, exhibit qualitative agreement with experimental observations by predicting the formation of liquid jets. Simulations also suggest that bubble-bubble interactions act to enhance surface mode instability. PMID- 22088008 TI - Natural frequencies of two bubbles in a compliant tube: analytical, simulation, and experimental results. AB - Motivated by various clinical applications of ultrasound contrast agents within blood vessels, the natural frequencies of two bubbles in a compliant tube are studied analytically, numerically, and experimentally. A lumped parameter model for a five degree of freedom system was developed, accounting for the compliance of the tube and coupled response of the two bubbles. The results were compared to those produced by two different simulation methods: (1) an axisymmetric coupled boundary element and finite element code previously used to investigate the response of a single bubble in a compliant tube and (2) finite element models developed in comsol Multiphysics. For the simplified case of two bubbles in a rigid tube, the lumped parameter model predicts two frequencies for in- and out of-phase oscillations, in good agreement with both numerical simulation and experimental results. For two bubbles in a compliant tube, the lumped parameter model predicts four nonzero frequencies, each asymptotically converging to expected values in the rigid and compliant limits of the tube material. PMID- 22088010 TI - Bubble dynamics in a standing sound field: the bubble habitat. AB - Bubble dynamics is investigated numerically with special emphasis on the static pressure and the positional stability of the bubble in a standing sound field. The bubble habitat, made up of not dissolving, positionally and spherically stable bubbles, is calculated in the parameter space of the bubble radius at rest and sound pressure amplitude for different sound field frequencies, static pressures, and gas concentrations of the liquid. The bubble habitat grows with static pressure and shrinks with sound field frequency. The range of diffusionally stable bubble oscillations, found at positive slopes of the habitat diffusion border, can be increased substantially with static pressure. PMID- 22088011 TI - Multiple observations of cavitation cluster dynamics close to an ultrasonic horn tip. AB - Bubble dynamics in water close to the tip of an ultrasonic horn (~23 kHz, 3 mm diameter) have been studied using electrochemistry, luminescence, acoustics, light scattering, and high-speed imaging. It is found that, under the conditions employed, a large bubble cluster (~1.5 mm radius) exists at the tip of the horn. This cluster collapses periodically every three to four cycles of the fundamental frequency of the horn. Following the collapse of the cluster, a short-lived cloud of small bubbles (each tens of microns in diameter) was observed in the solution. Large amplitude pressure emissions are also recorded, which correlate temporally with the cluster collapse. Bursts of surface erosion (measured in real time using an electrochemical technique) and multibubble sonoluminescence emission both also occur at a subharmonic of the fundamental frequency of the horn and are temporally correlated with the bubble cluster collapse and the associated pressure wave emission. PMID- 22088012 TI - Optical nucleation of bubble clouds in a high pressure spherical resonator. AB - An experimental setup for nucleating clouds of bubbles in a high-pressure spherical resonator is described. Using nanosecond laser pulses and multiple phase gratings, bubble clouds are optically nucleated in an acoustic field. Dynamics of the clouds are captured using a high-speed CCD camera. The images reveal cloud nucleation, growth, and collapse and the resulting emission of radially expanding shockwaves. These shockwaves are reflected at the interior surface of the resonator and then reconverge to the center of the resonator. As the shocks reconverge upon the center of the resonator, they renucleate and grow the bubble cloud. This process is repeated over many acoustic cycles and with each successive shock reconvergence, the bubble cloud becomes more organized and centralized so that subsequent collapses give rise to stronger, better defined shockwaves. After many acoustic cycles individual bubbles cannot be distinguished and the cloud is then referred to as a cluster. Sustainability of the process is ultimately limited by the detuning of the acoustic field inside the resonator. The nucleation parameter space is studied in terms of laser firing phase, laser energy, and acoustic power used. PMID- 22088013 TI - Consistency in statistical moments as a test for bubble cloud clustering. AB - Frequency dependent measurements of attenuation and/or sound speed through clouds of gas bubbles in liquids are often inverted to find the bubble size distribution and the void fraction of gas. The inversions are often done using an effective medium theory as a forward model under the assumption that the bubble positions are Poisson distributed (i.e., statistically independent). Under circumstances in which single scattering does not adequately describe the pressure field, the assumption of independence in position can yield large errors when clustering is present, leading to errors in the inverted bubble size distribution. It is difficult, however, to determine the existence of clustering in bubble clouds without the use of specialized acoustic or optical imaging equipment. A method is described here in which the existence of bubble clustering can be identified by examining the consistency between the first two statistical moments of multiple frequency acoustic measurements. PMID- 22088015 TI - The effect of wind-generated bubbles on sea-surface backscattering at 940 Hz. AB - Reliable predictions of sea-surface backscattering strength are required for sonar performance modeling. These are, however, difficult to obtain as measurements of sea-surface backscattering are not available at small grazing angles relevant to low-frequency active sonar (1-3 kHz). Accurate theoretical predictions of scattering strength require a good understanding of physical mechanisms giving rise to the scattering and the relative importance of these. In this paper, scattering from individual resonant bubbles is introduced as a potential mechanism and a scattering model is derived that incorporates the contribution from these together with that of rough surface scattering. The model results are fitted to Critical Sea Test (CST) measurements at a frequency of 940 Hz, treating the number of large bubbles, parameterized through the spectral slope of the size spectrum for bubbles whose radii exceed 1 mm, as a free parameter. This procedure illustrates that the CST data can be explained by scattering from a small number of large resonant bubbles, indicating that these provide an alternative mechanism to that of scattering from bubble clouds. PMID- 22088014 TI - The use of an air bubble curtain to reduce the received sound levels for harbor porpoises (Phocoena phocoena). AB - In December 2005 construction work was started to replace a harbor wall in Kerteminde harbor, Denmark. A total of 175 wooden piles were piled into the ground at the waters edge over a period of 3 months. During the same period three harbor porpoises were housed in a marine mammal facility on the opposite side of the harbor. All animals showed strong avoidance reactions after the start of the piling activities. As a measure to reduce the sound exposure for the animals an air bubble curtain was constructed and operated in a direct path between the piling site and the opening of the animals' semi-natural pool. The sound attenuation effect achieved with this system was determined by quantitative comparison of pile driving impulses simultaneously measured in front of and behind the active air bubble curtain. Mean levels of sound attenuation over a sequence of 95 consecutive pile strikes were 14 dB (standard deviation (s.d.) 3.4 dB) for peak to peak values and 13 dB (s.d. 2.5 dB) for SEL values. As soon as the air bubble curtain was installed and operated, no further avoidance reactions of the animals to the piling activities were apparent. PMID- 22088016 TI - Improvements to the methods used to measure bubble attenuation using an underwater acoustical resonator. AB - Active acoustic techniques are commonly used to measure oceanic bubble size distributions, by inverting the bulk acoustical properties of the water (usually the attenuation) to infer the bubble population. Acoustical resonators have previously been used to determine attenuation over a wide range of frequencies (10-200 kHz) in a single measurement, corresponding to the simultaneous measurement of a wide range of bubble sizes (20-300 MUm radii). However, there is now also considerable interest in acquiring measurements of bubbles with radii smaller than 16 MUm, since these are thought to be important for ocean optics and as tracers for near-surface flow. To extend the bubble population measurement to smaller radii, it is necessary to extend the attenuation measurements to higher frequencies. Although the principles of resonator operation do not change as the frequency increases, the assumptions previously made during the spectral analysis may no longer be valid. In order to improve the methods used to calculate attenuation from acoustical resonator outputs, a more complete analysis of the resonator operation is presented here than has been published previously. This approach allows for robust attenuation measurements over a much wider frequency range and enables accurate measurements from lower-quality spectral peaks. PMID- 22088017 TI - Clutter suppression and classification using twin inverted pulse sonar in ship wakes. AB - Twin inverted pulse sonar (TWIPS) is here deployed in the wake of a moored rigid inflatable boat (RIB) with propeller turning, and then in the wake of a moving tanker of 4580 dry weight tonnage (the Whitchallenger). This is done first to test its ability to distinguish between scatter from the wake and scatter from the seabed, and second to test its ability to improve detectability of the seabed through the wake, compared to conventional sonar processing techniques. TWIPS does this by distinguishing between linear and nonlinear scatterers and has the further property of distinguishing those nonlinear targets which scatter energy at the even-powered harmonics from those which scatter in the odd-powered harmonics. TWIPS can also, in some manifestations, require no range correction (and therefore does not require the a priori environment knowledge necessary for most remote detection technologies). PMID- 22088018 TI - Measurements of bubbles in sea water by nonstationary sound scattering. AB - Methods for the characterization of bubbles in sea water by acoustic scattering are analyzed. Nonstationary linear and nonlinear sound scattering methods are proposed. The transient linear and nonlinear sound scattering allows the scattering by resonant gas bubbles to be distinguished from the scattering by other microinhomogeneities. The application of parametric arrays in oceanic experiments, together with the broadband frequency analysis of the backscattering coefficient, allows information about bubbles in sea water to be obtained. Experimental results on sound scattering and gas bubble distribution functions are presented for different conditions in the ocean. PMID- 22088019 TI - Effect of temperature on rectified diffusion during ultrasound-induced heating. AB - Experimental observations of delayed-onset cavitation during ultrasound insonation have been suggested as being caused by a change in the size distribution of the bubble population due to rectified diffusion. To investigate this hypothesis, a single bubble model is used here to explore the effect of heating and the subsequent elevated temperatures on the rectified diffusion process. Numerical solution of the model, which includes the temperature dependences of seven relevant physical parameters, allows quantification of the change in the pressure threshold for rectified diffusion, as well as the importance of the bulk liquid saturation concentration in determining bubble evolution. Although elevated temperatures and liquid supersaturation reduce the rectified diffusion threshold, it remains coincident with the inertial cavitation thresholds at submicron bubble sizes at all temperatures. This observation suggests that changes in the nucleation environment, rather than bubble growth due to rectified diffusion, is a more likely cause of delayed-onset cavitation events. PMID- 22088020 TI - The effect of temperature and viscoelasticity on cavitation dynamics during ultrasonic ablation. AB - Inertial cavitation has been shown to enhance heating rates during high intensity focused ultrasound treatments. Cavitation dynamics will be affected by heating and by the changes in mechanical properties of tissue resultant from thermal denaturation; however, the nature of the change is not known and forms the focus of the current study. A Keller-Miksis equation is used to find the variation in inertial cavitation threshold with temperature in water and, when coupled with a Kelvin-Voigt viscoelastic model, in biological tissue. Simulated thermal ablation treatments in liver and muscle are used to explore the changes in cavitation dynamics, and the resultant frequency spectra of secondary acoustic emissions, due to tissue denaturation. Results indicate that viscosity is the key parameter controlling cavitation dynamics in biological tissues. The increase in viscosity during denaturation is predicted to increase inertial cavitation thresholds, leading to a substantial decrease in the higher harmonic content of the emitted pressure signal across a wide range of bubble radii. Experimental validation of these observations could offer improved methods to monitor therapeutic ultrasound treatments. PMID- 22088021 TI - Shear strain from irrotational tissue displacements near bubbles. AB - Particle displacements can be much greater near bubbles than they would be in a homogeneous liquid or tissue when exposed to an acoustic wave. In a plane wave, shear and bulk strains are of the same order of magnitude. In contrast, for a bubble oscillating close to its resonance frequency, the shear strain in the medium near the bubble is roughly four orders of magnitude greater than the bulk strain. This can lead to shear strains of a few percent even with acoustic excitation pressures far below the pressure thresholds required to cause inertial cavitation. High shear strains near oscillating bubbles could potentially be the cause of bioeffects. After acoustic exposures at audio frequencies, hemorrhages in tissues as diverse as lung, liver, and kidney have been observed at shear strains on the order of 1%. PMID- 22088022 TI - Acoustic characterization of echogenic liposomes: frequency-dependent attenuation and backscatter. AB - Ultrasound contrast agents (UCAs) are used clinically to aid detection and diagnosis of abnormal blood flow or perfusion. Characterization of UCAs can aid in the optimization of ultrasound parameters for enhanced image contrast. In this study echogenic liposomes (ELIPs) were characterized acoustically by measuring the frequency-dependent attenuation and backscatter coefficients at frequencies between 3 and 30 MHz using a broadband pulse-echo technique. The experimental methods were initially validated by comparing the attenuation and backscatter coefficients measured from 50-MUm and 100-MUm polystyrene microspheres with theoretical values. The size distribution of the ELIPs was measured and found to be polydisperse, ranging in size from 40 nm to 6 MUm in diameter, with the highest number observed at 65 nm. The ELIP attenuation coefficients ranged from 3.7 +/- 1.0 to 8.0 +/- 3.3 dB/cm between 3 and 25 MHz. The backscatter coefficients were 0.011 +/- 0.006 (cm str)(-1) between 6 and 9 MHz and 0.023 +/ 0.006 (cm str)(-1) between 13 and 30 MHz. The measured scattering-to-attenuation ratio ranged from 8% to 22% between 6 and 25 MHz. Thus ELIPs can provide enhanced contrast over a broad range of frequencies and the scattering properties are suitable for various ultrasound imaging applications including diagnostic and intravascular ultrasound. PMID- 22088024 TI - Passive cavitation mapping with temporal sparsity constraint. AB - The spatial resolution of cavitation maps generated from passive recordings of cavitation emissions is compromised by the bandlimited nature of the recordings. Deconvolution based on the assumption that cavitation consists of a sparse series of discrete events allows the recovery of frequency components that are not only outside the frequency band of the receivers, but may also have been attenuated by the medium before being detectable. In the current work, two sparse deconvolution techniques, matching pursuit and basis pursuit, were applied to simulated and experimental cavitation recordings before they were beamformed to provide passive maps of cavitation activity. Matching pursuit was shown to reduce the maximal diameter of the point spread function by almost a third, at the cost of greater susceptibility to inter-source interference. In contrast, although basis pursuit causes an almost 20% increase in the maximal diameter of the point spread function, its application to experimental data appears to enhance the ability of passive mapping to resolve multiple sources. PMID- 22088023 TI - The influence of octyl beta-D-glucopyranoside on cell lysis induced by ultrasonic cavitation. AB - Octyl beta-D-glucopyranoside (OGP) has been reported to completely inhibit cavitation-induced cell lysis in vitro, possibly by quenching critical free radical effects. In this study, the influence of OGP on cell lysis in a 60 rpm rotating-tube exposure apparatus was assessed. HL-60 cell lysis was estimated with a Coulter Multisizer counter. Cavitation activity from the 2.3 MHz, 30 s duration exposures were monitored at the 1.15 MHz subharmonic. Cavitation nucleation was accomplished by addition of an ultrasound contrast agent, or by using freshly dissolved culture media. For both nucleation methods, exposures were conducted for 0-0.7 MPa peak rarefactional pressure-amplitudes with and without 5 mM OGP, and for 0.5 MPa with 0-5 mM OGP. The addition of OGP to the cell suspension medium generally had little influence on cavitation-induced cell lysis. Exposures with no rotation had reduced subharmonic and lysis for added contrast agent, but essentially no cavitation for the fresh medium. Since the decreases or increases in cell lysis found for added OGP generally were accounted for by concomitant decreases or increases in cavitation activity, the changes in cell lysis could be explained by variation of the mechanical effects of cavitation without invoking a critical role for free-radical effects. PMID- 22088025 TI - Controlled tissue emulsification produced by high intensity focused ultrasound shock waves and millisecond boiling. AB - In high intensity focused ultrasound (HIFU) applications, tissue may be thermally necrosed by heating, emulsified by cavitation, or, as was recently discovered, emulsified using repetitive millisecond boiling caused by shock wave heating. Here, this last approach was further investigated. Experiments were performed in transparent gels and ex vivo bovine heart tissue using 1, 2, and 3 MHz focused transducers and different pulsing schemes in which the pressure, duty factor, and pulse duration were varied. A previously developed derating procedure to determine in situ shock amplitudes and the time-to-boil was refined. Treatments were monitored using B-mode ultrasound. Both inertial cavitation and boiling were observed during exposures, but emulsification occurred only when shocks and boiling were present. Emulsified lesions without thermal denaturation were produced with shock amplitudes sufficient to induce boiling in less than 20 ms, duty factors of less than 0.02, and pulse lengths shorter than 30 ms. Higher duty factors or longer pulses produced varying degrees of thermal denaturation combined with mechanical emulsification. Larger lesions were obtained using lower ultrasound frequencies. The results show that shock wave heating and millisecond boiling is an effective and reliable way to emulsify tissue while monitoring the treatment with ultrasound. PMID- 22088026 TI - A reduced-order, single-bubble cavitation model with applications to therapeutic ultrasound. AB - Cavitation often occurs in therapeutic applications of medical ultrasound such as shock-wave lithotripsy (SWL) and high-intensity focused ultrasound (HIFU). Because cavitation bubbles can affect an intended treatment, it is important to understand the dynamics of bubbles in this context. The relevant context includes very high acoustic pressures and frequencies as well as elevated temperatures. Relative to much of the prior research on cavitation and bubble dynamics, such conditions are unique. To address the relevant physics, a reduced-order model of a single, spherical bubble is proposed that incorporates phase change at the liquid-gas interface as well as heat and mass transport in both phases. Based on the energy lost during the inertial collapse and rebound of a millimeter-sized bubble, experimental observations were used to tune and test model predictions. In addition, benchmarks from the published literature were used to assess various aspects of model performance. Benchmark comparisons demonstrate that the model captures the basic physics of phase change and diffusive transport, while it is quantitatively sensitive to specific model assumptions and implementation details. Given its performance and numerical stability, the model can be used to explore bubble behaviors across a broad parameter space relevant to therapeutic ultrasound. PMID- 22088027 TI - Observations of the collapses and rebounds of millimeter-sized lithotripsy bubbles. AB - Bubbles excited by lithotripter shock waves undergo a prolonged growth followed by an inertial collapse and rebounds. In addition to the relevance for clinical lithotripsy treatments, such bubbles can be used to study the mechanics of inertial collapses. In particular, both phase change and diffusion among vapor and noncondensable gas molecules inside the bubble are known to alter the collapse dynamics of individual bubbles. Accordingly, the role of heat and mass transport during inertial collapses is explored by experimentally observing the collapses and rebounds of lithotripsy bubbles for water temperatures ranging from 20 to 60 degrees C and dissolved gas concentrations from 10 to 85% of saturation. Bubble responses were characterized through high-speed photography and acoustic measurements that identified the timing of individual bubble collapses. Maximum bubble diameters before and after collapse were estimated and the corresponding ratio of volumes was used to estimate the fraction of energy retained by the bubble through collapse. The rebounds demonstrated statistically significant dependencies on both dissolved gas concentration and temperature. In many observations, liquid jets indicating asymmetric bubble collapses were visible. Bubble rebounds were sensitive to these asymmetries primarily for water conditions corresponding to the most dissipative collapses. PMID- 22088028 TI - Cross-language acoustic similarity predicts perceptual assimilation of Canadian English and Canadian French vowels. AB - Monolingual Peruvian Spanish listeners identified natural tokens of the Canadian French (CF) and Canadian English (CE) /E/ and /ae/, produced in five consonantal contexts. The results demonstrate that while the CF vowels were mapped to two different native vowels, /e/ and /a/, in all consonantal contexts, the CE contrast was mapped to the single native vowel /a/ in four out of five contexts. Linear discriminant analysis revealed that acoustic similarity between native and target language vowels was a very good predictor of context-specific perceptual mappings. Predictions are made for Spanish learners of the /E/-/ae/ contrast in CF and CE. PMID- 22088029 TI - Detection of multicomponent signals: effect of difference in level between components. AB - The detection of multicomponent signals for which the components are not equidetectable is precisely investigated as a function of the level difference DeltaL(i/j) between components. The detection thresholds are determined for a seven-tone complex signal with random starting phases masked by white noise. Level differences between the components are examined. A model for non equidetectable conditions based on the statistical summation model is described. The improvement in detection is calculated from the level difference between components that is related to the thresholds for single components. The model predictions are in accordance with the experimental results. PMID- 22088030 TI - Coherence masking protection for mid-frequency formants by adults and children. AB - Coherence masking protection (CMP) refers to the phenomenon in which a target formant is labeled at lower signal-to-noise levels when presented with a stable cosignal consisting of two other formants than when presented alone. This effect has been reported primarily for adults with first-formant (F1) targets and F2/F3 cosignals, but has also been found for children, in fact in greater magnitude. In this experiment, F2 was the target and F1/F3 was the cosignal. Results showed similar effects for each age group as had been found for F1 targets. Implications for auditory prostheses for listeners with hearing loss are discussed. PMID- 22088031 TI - Cross-language specialization in phonetic processing: English and Hindi perception of /w/-/v/ speech and nonspeech. AB - This study examined the perceptual specialization for native-language speech sounds, by comparing native Hindi and English speakers in their perception of a graded set of English /w/-/v/ stimuli that varied in similarity to natural speech. The results demonstrated that language experience does not affect general auditory processes for these types of sounds; there were strong cross-language differences for speech stimuli, and none for stimuli that were nonspeech. However, the cross-language differences extended into a gray area of speech-like stimuli that were difficult to classify, suggesting that the specialization occurred in phonetic processing prior to categorization. PMID- 22088032 TI - A subspace approach based on embedded prewhitening for voice activity detection. AB - This paper presents a subspace approach for voice activity detection (VAD). The proposed approach is based on an embedded prewhitening scheme for the simultaneous diagonalization of the clean speech and noise covariance matrices to provide a decision rule based on likelihood ratio test in signal subspace domain. Experimental results show that the proposed subspace-based VAD algorithm outperforms the method using a Gaussian model in a conventional discrete Fourier transform domain at the low signal-to-noise conditions. PMID- 22088033 TI - Horns as particle velocity amplifiers. AB - Preliminary measurements and numerical predictions reveal that simple, and relatively small, horns generate remarkable amplification of acoustic particle velocity. For example, below 2 kHz, a 2.5 cm conical horn has a uniform velocity amplification ratio (throat-to-mouth) factor of approximately 3, or, in terms of a decibel level, 9.5 dB. It is shown that the velocity amplification factor depends on the horn's mouth-to-throat ratio as well as, though to a lesser degree, the horn's flare rate. A double horn configuration provides limited additional gain, approximately an increase of up to 25%. PMID- 22088034 TI - Waveguide invariant analysis for modeling time-frequency striations in a range dependent environment. AB - The waveguide invariant is a useful parameter for understanding the behavior of interference patterns (e.g., striations in time-frequency plots) resulting from broadband acoustic sources in shallow water waveguides. It is possible to model these striations for range-dependent environments using conventional parabolic equation methods; although this approach can be computationally intensive as a full field must be created for each frequency and azimuthally dependent geometry. This letter discusses the formulation and use of a range-dependent waveguide invariant distribution that can be used to describe spectral striation patterns using a fraction of the computing power required by parabolic equation methods. PMID- 22088035 TI - The redundancy of phonemes in sentential context. AB - Printed English is highly redundant as demonstrated by readers' facility at guessing which letter comes next in text. However, such findings have been generalized to perception of connected speech without any direct assessment of phonemic redundancy. Here, participants guessed which phoneme or printed character came next throughout each of four unrelated sentences. Phonemes displayed significantly lower redundancy than letters, and possible contributing factors (task difficulty, experience, context) are discussed. Of three models tested, phonemic guessing was best approximated by word-initial and transitional probabilities between phonemes. Implications for information-theoretic accounts of speech perception are considered. PMID- 22088036 TI - Effect of decision weights and internal noise on the growth of d' with N. AB - A general finding of psychoacoustic studies is that detectability d' of a noisy signal grows less than optimally with the number N of independent observations of the signal. Competing accounts implicate internal noise common to all observations or nonoptimal decision weights given to observations. A discriminant analysis of listeners' trial-by-trial responses in a multitone level discrimination task favored the latter account. PMID- 22088037 TI - Three-dimensional impedance map analysis of rabbit liver. AB - Three-dimensional impedance maps (3DZMs) are computational models of acoustic impedance of tissue constructed from histology images. 3DZMs can be analyzed to estimate model-based quantitative ultrasound parameters such as effective scatterer diameter (ESD). In this study, 3DZMs were constructed from normal and fatty rabbit livers. Estimates of ESD were made using the fluid-filled sphere scattering model. Weighting toward smaller scatterer sizes produced ESD estimates of 7.5 +/- 1.3 and 7.0 +/- 0.3 MUm for normal and fatty liver, respectively, approximately the size of a liver cell nucleus. This suggests the nucleus could be a primary source of scattering in liver. PMID- 22088038 TI - Description of sounds recorded from Longman's beaked whale, Indopacetus pacificus. AB - Sounds from Longman's beaked whale, Indopacetus pacificus, were recorded during shipboard surveys of cetaceans surrounding the Hawaiian Islands archipelago; this represents the first known recording of this species. Sounds included echolocation clicks and burst pulses. Echolocation clicks were grouped into three categories, a 15 kHz click (n = 106), a 25 kHz click (n = 136), and a 25 kHz pulse with a frequency-modulated upsweep (n = 70). The 15 and 25 kHz clicks were relatively short (181 and 144 ms, respectively); the longer 25 kHz upswept pulse was 288 ms. Burst pulses were long (0.5 s) click trains with approximately 240 clicks/s. PMID- 22088039 TI - Lateral reflections are favorable in concert halls due to binaural loudness. AB - A recent study on perceptual difference in simulated concert halls showed that a concert hall renders stronger sound with more bass when the temporal envelope of a signal is preserved in the reflections [Lokki et al., J. Acoust. Soc. Am. 129, EL223-EL228 (2011)]. In the same study the lateral reflections were shown to contribute to the perceived envelopment and openness. Moreover, the listening test results suggest that lateral reflections contribute to perception of sound source distance. Here, it is shown that lateral reflections are beneficial due to their increasing effect on binaural loudness-the phenomenon known well in psychoacoustics, but not in architectural acoustics. The reflections from the side are amplified more than median plane reflections, in particular at high frequencies, due to the shape of the human head. PMID- 22088040 TI - Non-isomorphism in efficient coding of complex sound properties. AB - To the extent that sensorineural systems are efficient, stimulus redundancy should be captured in ways that optimize information transmission. Consistent with this principle, neural representations of sounds have been proposed to become "non-isomorphic," increasingly abstract and decreasingly resembling the original (redundant) input. Here, non-isomorphism is tested in perceptual learning using AXB discrimination of novel sounds with two highly correlated complex acoustic properties and a randomly varying third dimension. Discrimination of sounds obeying the correlation became superior to that of sounds violating it despite widely varying physical acoustic properties, suggesting non-isomorphic representation of stimulus redundancy. PMID- 22088041 TI - Interaural spectral asymmetry and sensitivity to interaural time differences. AB - Listeners' ability to discriminate interaural time difference (ITD) changes in low-frequency noise was determined as a function of differences in the noise spectra delivered to each ear. An ITD was applied to Gaussian noise, which was bandpass filtered using identical high-pass, but different low-pass cutoff frequencies across ears. Thus, one frequency region was dichotic, and a higher frequency region monotic. ITD thresholds increased as bandwidth to one ear (i.e., monotic bandwidth) increased, despite the fact that the region of interaural spectral overlap remained constant. Results suggest that listeners can process ITD differences when the spectra at two ears are moderately different. PMID- 22088043 TI - Communication: regularizing binding energy distributions and thermodynamics of hydration: theory and application to water modeled with classical and ab initio simulations. AB - The high-energy tail of the distribution of solute-solvent interaction energies is poorly characterized for condensed systems, but this tail region is of principal interest in determining the excess free energy of the solute. We introduce external fields centered on the solute to modulate the short-range repulsive interaction between the solute and solvent. This regularizes the binding energy distribution and makes it easy to calculate the free energy of the solute with the field. Together with the work done to apply the field in the presence and absence of the solute, we calculate the excess chemical potential of the solute. We present the formal development of this idea and apply it to study liquid water. PMID- 22088042 TI - Covariation among vowel height effects on acoustic measures. AB - Covariation among vowel height effects on vowel intrinsic fundamental frequency (IF(0)), voice onset time (VOT), and voiceless interval duration (VID) is analyzed to assess the plausibility of a common physiological mechanism underlying variation in these measures. Phrases spoken by 20 young adults, containing words composed of initial voiceless stops or /s/ and high or low vowels, were produced in habitual and voluntarily increased F(0) conditions. High vowels were associated with increased IF(0) and longer VIDs. VOT and VID exhibited significant covariation with IF(0) only for males at habitual F(0). The lack of covariation for females and at increased F(0) is discussed. PMID- 22088044 TI - Communication: inferring the equation of state of a metastable hard-sphere fluid from the equation of state of a hard-sphere mixture at high densities. AB - A possible approximate route to obtain the equation of state of the monodisperse hard-sphere system in the metastable fluid region from the knowledge of the equation of state of a hard-sphere mixture at high densities is discussed. The proposal is illustrated by using recent Monte Carlo simulation data for the pressure of a binary mixture. It is further shown to exhibit high internal consistency. PMID- 22088045 TI - Communication: limitations of the stochastic quasi-steady-state approximation in open biochemical reaction networks. AB - It is commonly believed that, whenever timescale separation holds, the predictions of reduced chemical master equations obtained using the stochastic quasi-steady-state approximation are in very good agreement with the predictions of the full master equations. We use the linear noise approximation to obtain a simple formula for the relative error between the predictions of the two master equations for the Michaelis-Menten reaction with substrate input. The reduced approach is predicted to overestimate the variance of the substrate concentration fluctuations by as much as 30%. The theoretical results are validated by stochastic simulations using experimental parameter values for enzymes involved in proteolysis, gluconeogenesis, and fermentation. PMID- 22088046 TI - Semi-bottom-up coarse graining of water based on microscopic simulations. AB - The generalized dissipative particle dynamics (DPD) equation derived from the generalized Langevin equation under Markovian approximations is used to simulate coarse-grained (CG) water cells. The mean force and the friction coefficients in the radial and transverse directions needed for DPD equation are obtained directly from the all atomistic molecular dynamics (AAMD) simulations. But the dissipative friction forces are overestimated in the Markovian approximation, which results in wrong dynamic properties for the CG water in the DPD simulations. To account for the non-Markovian dynamics, a rescaling factor is introduced to the friction coefficients. The value of the factor is estimated by matching the diffusivity of water. With this semi-bottom-up mapping method, the radial distribution function, the diffusion constant, and the viscosity of the coarse-grained water system computed with DPD simulations are all in good agreement with AAMD results. It bridges the microscopic level and mesoscopic level with consistent length and time scales. PMID- 22088047 TI - Photodissociation of methyl iodide embedded in a host-guest complex: a full dimensional (189D) quantum dynamics study of CH3I@resorc[4]arene. AB - Accurate full dimensional quantum dynamics calculations studying the photodissociation of CH(3)I@resorc[4]arene on an ab initio based potential energy surface (PES) model are reported. The converged 189D quantum dynamics calculations are facilitated by the multilayer multi-configurational time dependent Hartree (ML-MCTDH) approach combined with the correlation discrete variable representation (CDVR) for the evaluation of potential energy matrix elements. The potential employed combines an established ab initio PES describing the photodissociation of methyl iodide in the A band with a harmonic description of the resorc[4]arene host and a bilinear modeling of the host-guest interaction. All potential parameters required in the description of the vibrations of the host molecule and the host-guest interaction are derived from ab initio calculations on the host-guest complex. Absorption spectra at 0 K and 300 K are calculated and the electronic population dynamics during the bond breaking process occurring in the first 20-30 fs after the photoexcitation is investigated. Weak but significant effects resulting from the host-guest interaction on this time scale are found and interpreted. The present study demonstrates that accurate fully quantum mechanical dynamics calculations can be preformed for systems consisting of more than 50 atoms using the ML-MCTDH/CDVR approach. Utilizing an efficient statistical approach for the construction of the ensemble of initial wavepackets, these calculations are not restricted to zero temperature but can also study the dynamics at 300 K. PMID- 22088048 TI - A semi-grand canonical Monte Carlo simulation model for ion binding to ionizable surfaces: proton binding of carboxylated latex particles as a case study. AB - In this paper, we present a computer simulation study of the ion binding process at an ionizable surface using a semi-grand canonical Monte Carlo method that models the surface as a discrete distribution of charged and neutral functional groups in equilibrium with explicit ions modelled in the context of the primitive model. The parameters of the simulation model were tuned and checked by comparison with experimental titrations of carboxylated latex particles in the presence of different ionic strengths of monovalent ions. The titration of these particles was analysed by calculating the degree of dissociation of the latex functional groups vs. pH curves at different background salt concentrations. As the charge of the titrated surface changes during the simulation, a procedure to keep the electroneutrality of the system is required. Here, two approaches are used with the choice depending on the ion selected to maintain electroneutrality: counterion or coion procedures. We compare and discuss the difference between the procedures. The simulations also provided a microscopic description of the electrostatic double layer (EDL) structure as a function of pH and ionic strength. The results allow us to quantify the effect of the size of the background salt ions and of the surface functional groups on the degree of dissociation. The non-homogeneous structure of the EDL was revealed by plotting the counterion density profiles around charged and neutral surface functional groups. PMID- 22088049 TI - The nuclear magnetic resonance relaxation data analysis in solids: general R1/R1(rho) equations and the model-free approach. AB - The advantage of the solid state NMR for studying molecular dynamics is the capability to study slow motions without limitations: in the liquid state, if orienting media are not used, all anisotropic magnetic interactions are averaged out by fast overall Brownian tumbling of a molecule and thus investigation of slow internal conformational motions (e.g., of proteins) in solution can be conducted using only isotropic interactions. One of the main tools for obtaining amplitudes and correlation times of molecular motions in the MUs time scale is measuring relaxation rate R(1)(rho). Yet, there have been a couple of unresolved problems in the quantitative analysis of the relaxation rates. First, when the resonance offset of the spin-lock pulse is used, the spin-lock field can be oriented under an arbitrary angle in respect to B(0). Second, the spin-lock frequency can be comparable or even less than the magic angle spinning rate. Up to now, there have been no equations for R(1)(rho) that would be applicable for any values of the spin-lock frequency, magic angle spinning rate and resonance offset of the spin-lock pulse. In this work such equations were derived for two most important relaxation mechanisms: heteronuclear dipolar coupling and chemical shift anisotropy. The validity of the equations was checked by numerical simulation of the R(1)(rho) experiment using SPINEVOLUTION program. In addition to that, the applicability of the well-known model-free approach to the solid state NMR relaxation data analysis was considered. For the wobbling in a cone at 30 degrees and 90 degrees cone angles and two-site jump models, it has been demonstrated that the auto-correlation functions G(0)(t), G(1)(t), G(2)(t), corresponding to different spherical harmonics, for isotropic samples (powders, polycrystals, etc.) are practically the same regardless of the correlation time of motion. This means that the model-free approach which is widely used in liquids can be equally applied, at least assuming these two motional models, to the analysis of the solid state NMR relaxation data. PMID- 22088050 TI - Calculation of the exchange coupling constants of copper binuclear systems based on spin-flip constricted variational density functional theory. AB - We have recently developed a methodology for the calculation of exchange coupling constants J in weakly interacting polynuclear metal clusters. The method is based on unrestricted and restricted second order spin-flip constricted variational density functional theory (SF-CV(2)-DFT) and is here applied to eight binuclear copper systems. Comparison of the SF-CV(2)-DFT results with experiment and with results obtained from other DFT and wave function based methods has been made. Restricted SF-CV(2)-DFT with the BH&HLYP functional yields consistently J values in excellent agreement with experiment. The results acquired from this scheme are comparable in quality to those obtained by accurate multi-reference wave function methodologies such as difference dedicated configuration interaction and the complete active space with second-order perturbation theory. PMID- 22088051 TI - Multipolar polarizabilities and two-body dispersion coefficients for Na by a variationally stable procedure. AB - Based on the weakest bound electron potential model theory, the ground-state wave function of Na is investigated. The variationally stable procedure of Gao and Starace is then employed to evaluate the static multipolar polarizabilities of Na, and the two-body dispersion coefficients for the Na-Na system. Calculated values show that our results are in general agreement with those previously reported in the literature. PMID- 22088052 TI - A tiered approach to Monte Carlo sampling with self-consistent field potentials. AB - A "tiered" approach to Monte Carlo sampling of nuclear configurations is presented for ab initio, self-consistent field (SCF)-based potentials, including Hartree-Fock and density functional theory. Rather than Metropolis testing only the final SCF energy, individual cycle energies are tested in a tiered fashion, without approximation. Accordingly, rejected configurations are terminated early in the SCF procedure. The method is shown to properly obey detailed balance, and effective modifications are presented for cases in which the initial SCF guess is particularly poor. Demonstrations on simple systems are provided, including an assessment of the thermal properties of the neutral water dimer with B3LYP/6 31++G**. Cost analysis indicates a factor-of-two reduction in SCF cycles, which makes the method competitive with accelerated molecular dynamics sampling techniques, without the need for forces. PMID- 22088053 TI - Magnetic exchange couplings from constrained density functional theory: an efficient approach utilizing analytic derivatives. AB - We introduce a method for evaluating magnetic exchange couplings based on the constrained density functional theory (C-DFT) approach of Rudra, Wu, and Van Voorhis [J. Chem. Phys. 124, 024103 (2006)]. Our method shares the same physical principles as C-DFT but makes use of the fact that the electronic energy changes quadratically and bilinearly with respect to the constraints in the range of interest. This allows us to use coupled perturbed Kohn-Sham spin density functional theory to determine approximately the corrections to the energy of the different spin configurations and construct a priori the relevant energy landscapes obtained by constrained spin density functional theory. We assess this methodology in a set of binuclear transition-metal complexes and show that it reproduces very closely the results of C-DFT. This demonstrates a proof-of concept for this method as a potential tool for studying a number of other molecular phenomena. Additionally, routes to improving upon the limitations of this method are discussed. PMID- 22088054 TI - Prospects for release-node quantum Monte Carlo. AB - We perform release-node quantum Monte Carlo simulations on the first row diatomic molecules in order to assess how accurately their ground-state energies can be obtained. An analysis of the fermion-boson energy difference is shown to be strongly dependent on the nuclear charge, Z, which in turn determines the growth of variance of the release-node energy. It is possible to use maximum entropy analysis to extrapolate to ground-state energies only for the low Z elements. For the higher Z dimers beyond boron, the error growth is too large to allow accurate data for long enough imaginary times. Within the limit of our statistics we were able to estimate, in atomic units, the ground-state energy of Li(2) ( 14.9947(1)), Be(2) (-29.3367(7)), and B(2)(-49.410(2)). PMID- 22088055 TI - Particle-particle particle-mesh method for dipolar interactions: on error estimates and efficiency of schemes with analytical differentiation and mesh interlacing. AB - The interlaced and non-interlaced versions of the dipolar particle-particle particle-mesh (P(3)M) method implemented using the analytic differentiation scheme (AD-P(3)M) are presented together with their respective error estimates for the calculation of the forces, torques, and energies. Expressions for the optimized lattice Green functions, and for the Madelung self-forces, self-torques and self-energies are given. The applicability of the theoretical error estimates are thoroughly tested and confirmed in several numerical examples. Our results show that the accuracy of the calculations can be improved substantially when the approximate (mesh computed) Madelung self-interactions are subtracted. Furthermore, we show that the interlaced dipolar AD-P(3)M method delivers a significantly higher accuracy (which corresponds approximately to using a twice finer mesh) than the conventional method, allowing thereby to reduce the mesh size with respect to the non-interlaced version for a given accuracy. In addition, we present similar expressions for the dipolar ik-differentiation interlaced scheme, and we perform a comparison with the AD interlaced scheme. Rough tests for the relative speed of the dipolar P(3)M method using ik differentiation and the interlaced/non-interlaced AD schemes show that when FFT computing time is the bottleneck, usually when working at high precisions, the interlaced AD-scheme can be several times faster than the other two schemes. For calculations with a low accuracy requirement, the interlaced version can perform worse than the ik and the non-interlaced AD schemes. PMID- 22088056 TI - Analytical approach for the excited-state Hessian in time-dependent density functional theory: formalism, implementation, and performance. AB - The paper presents the formalism, implementation, and performance of the analytical approach for the excited-state Hessian in the time-dependent density functional theory (TDDFT) that extends our previous work [J. Liu and W. Z. Liang, J. Chem. Phys. 135, 014113 (2011)] on the analytical Hessian in TDDFT within Tamm Dancoff approximation (TDA) to full TDDFT. In contrast to TDA-TDDFT, an appreciable advantage of full TDDFT is that it maintains the oscillator strength sum rule, and therefore yields more precise results for the oscillator strength and other related physical quantities. For the excited-state harmonic vibrational frequency calculation, however, full TDDFT does not seem to be advantageous since the numerical tests demonstrate that the accuracy of TDDFT with and without TDA are comparable to each other. As a common practice, the computed harmonic vibrational frequencies are scaled by a suitable scale factor to yield good agreement with the experimental fundamental frequencies. Here we apply both the optimized ground-state and excited-state scale factors to scale the calculated excited-state harmonic frequencies and find that the scaling decreases the root mean-square errors. The optimized scale factors derived from the excited-state calculations are slightly smaller than those from the ground-state calculations. PMID- 22088057 TI - Micro-imaging of transient guest profiles in nanochannels. AB - Zeolites of type ferrierite are exploited as a host system for monitoring the evolution of guest concentration (methanol) in nanoporous host materials upon adsorption. Additional transport resistances at the crystal surface have been removed so that uptake is exclusively controlled by the diffusion resistance of the pore space. Since the crystal shape deviates from a simple parallelepiped, the primary imaging data do not immediately reflect true local concentrations. A simple algorithm is developed which overcomes this complication. The determined transient concentration profiles ideally comply with the requirements for the application of the Boltzmann-Matano integration method for determining diffusivities. The resulting diffusivities (along the direction of the "10-ring channels") are found to exceed those along the 8-ring channels by three orders of magnitude. PMID- 22088058 TI - Can stimulated Raman pumping cause large population transfers in isolated molecules? AB - When stimulated Raman pumping (SRP) is applied to a stream of isolated molecules, such as found in a supersonic molecular beam expansion, we show that SRP can neither saturate nor power broaden a molecular transition connecting two metastable levels that is resonant with the energy difference between the pump and Stokes laser pulses. Using the optical Bloch-Feynman equations, we discuss the pumping of the hydrogen molecule from H(2) (v = 0, J = 0, M = 0) to H(2) (v = 1, J = 2, M = 0) as an illustration of how coherent population return severely reduces the SRP pumping efficiency unless the pump and Stokes laser pulses are applied with an appropriate relative delay and ratio of intensities. PMID- 22088059 TI - Resonance electron attachment and long-lived negative ions of phthalimide and pyromellitic diimide. AB - Resonance attachment of low energy (0-15 eV) electrons to imide-containing molecules, phthalimide (PTI) and pyromellitic diimide (PMDI), was investigated in the gas-phase by means of Electron Transmission Spectroscopy (ETS) and Dissociative Electron Attachment Spectroscopy (DEAS). Among a variety of low intensity negatively charged fragments formed by DEA, in both compounds the dominant species was found to be a long-lived (MUs) parent molecular anion formed at zero energy. In addition, in PMDI long-lived molecular anions were also observed at 0.85 and 2.0 eV. The experimentally evaluated detachment times from the molecular anions as a function of incident electron energy are modeled with a simple computational approach based on the RRKM theory. The occurrence of radiationless transitions to the ground anion state, followed by internal vibrational relaxation, is believed to be a plausible mechanism to explain the exceptionally long lifetime of the PMDI molecular anions formed above zero energy. PMID- 22088060 TI - Spin-orbit and rotational couplings in radiative association of C(3P) and N(4S) atoms. AB - The role of spin-orbit and rotational couplings in radiative association of C((3)P) and N((4)S) atoms is investigated. Couplings among doublet electronic states of the CN radical are considered, giving rise to a 6-state model of the process. The solution of the dynamical problem is based on the L(2) method, where a complex absorbing potential is added to the Hamiltonian operator in order to treat continuum and bound levels in the same manner. Comparison of the energy dependent rate coefficients calculated with and without spin-orbit and rotational couplings shows that the couplings have a strong effect on the resonance structure and low-energy baseline of the rate coefficient. PMID- 22088061 TI - Millimeter-wave rotational spectroscopy of FeCN (X 4Deltai) and FeNC (X 6Deltai): determining the lowest energy isomer. AB - The pure rotational spectrum of FeCN has been recorded in the frequency range 140 500 GHz using millimeter/sub-millimeter direct absorption techniques. The species was created in an ac discharge of Fe(CO)(5) and cyanogen. Spectra of the (13)C, (54)Fe, and (57)Fe isotopologues were also measured, confirming the linear cyanide structure of this free radical. Lines originating from several Renner Teller components in the nu(2) bending mode were also observed. Based on the observed spin-orbit pattern, the ground state of FeCN is (4)Delta(i), with small lambda-doubling splittings apparent in the Omega = 5/2, 3/2, and 1/2 components. In addition, a much weaker spectrum of the lowest spin-orbit component of FeNC, Omega = 9/2, was recorded; these data are consistent with the rotational parameters of previous optical studies. The data for FeCN were fit with a Hund's case (a) Hamiltonian and rotational, spin-orbit, spin-spin, and lambda-doubling parameters were determined. Rotational constants were also established from a case (c) analysis for the other isotopologues, excited vibronic states, and for FeNC. The r(0) bond lengths of FeCN were determined to be r(Fe-C) = 1.924 A and r(C-N) = 1.157 A, in agreement with theoretical predictions for the (4)Delta(i) state. These measurements indicate that FeCN is the lower energy isomer and is more stable than FeNC by ~1.9 kcal/mol. PMID- 22088062 TI - Spectroscopic studies of the A-X electronic spectrum of the beta hydroxyethylperoxy radical: structure and dynamics. AB - The jet-cooled A-X near IR origin band spectra of the G(1)G(2)G(3) conformer of four beta-hydroxyethylperoxy isotopologues, beta-HEP (HOCH(2)CH(2)OO), beta-DHEP (DOCH(2)CH(2)OO), beta-HEP-d(4) (HOCD(2)CD(2)OO), and beta-DHEP-d(4) (DOCD(2)CD(2)OO), have been recorded by a cavity ringdown spectrometer with a laser source linewidth of ~70 MHz. The spectra of all four isotopologues have been analyzed and successfully simulated with an evolutionary algorithm, confirming the cyclic structure of the molecule responsible for the observed origin band. The analysis also provides experimental A and X state rotational constants and the orientation of the transition dipole moment in the inertial axis system; these quantities are compared to results from electronic structure calculations. The observed, broad linewidth (Deltanu > 2 GHz) is attributed to a shortened lifetime of the A state associated with dynamics along the reaction path for hydrogen transfer from the OH to OO group. PMID- 22088063 TI - Lowest-energy structures and electronic properties of Na-Si binary clusters from ab initio global search. AB - The ground state structures of neutral and anionic clusters of Na(n)Si(m) (1 <= n <= 3, 1 <= m <= 11) have been determined using genetic algorithm incorporated in first principles total energy code. The size dependence of the structural and electronic properties is discussed in detail. It is found that the lowest-energy structures of Na(n)Si(m) clusters resemble those of the pure Si clusters. Interestingly, Na atoms in neutral Na(n)Si(m) clusters are usually well separated by the Si(m) skeleton, whereas Na atoms can form Na-Na bonds in some anionic clusters. The ionization potentials, adiabatic electron affinities, and photoelectron spectra are also calculated and the results compare well with the experimental data. PMID- 22088064 TI - Comparison of P...D (D = P,N) with other noncovalent bonds in molecular aggregates. AB - All the minima on the potential energy surfaces of homotrimers and tetramers of PH(3) are identified and analyzed as to the source of their stability. The same is done with mixed trimers in which one PH(3) molecule is replaced by either NH(3) or PFH(2). The primary noncovalent attraction in all global minima is the BP...D (D = N,P) bond which is characterized by the transfer of charge from a lone pair of the donor D to a sigma* B-P antibond of the partner molecule which is turned away from D, the same force earlier identified in the pertinent dimers. Examination of secondary minima reveals the presence of other weaker forces, some of which do not occur within the dimers. Examples of the latter include PH...P, NH...P, and PH...F H-bonds, and "reverse" H-bonds in which the source of the electron density is the smaller tail lobe of the donor lone pair. The global minima are cyclic structures in all cases, and exhibit some cooperativity, albeit to a small degree. The energy spacing of the oligomers is much smaller than that in the corresponding strongly H-bonded complexes such as the water trimer. PMID- 22088065 TI - Characterizing molecular motion in H2O and H3O+ with dynamical instability statistics. AB - Sets of finite-time Lyapunov exponents characterize the stability and instability of classically chaotic dynamical trajectories. Here we show that their sample distributions can contain subpopulations identifying different types of dynamics. In small isolated molecules these dynamics correspond to distinct elementary motions, such as isomerizations. Exponents are calculated from constant total energy molecular dynamics simulations of H(2)O and H(3)O(+), modelled with a classical, reactive, all-atom potential. Over a range of total energy, exponent distributions for these systems reveal that phase space exploration is more chaotic near saddles corresponding to isomerization and less chaotic near potential energy minima. This finding contrasts with previous results for Lennard Jones clusters, and is explained in terms of the potential energy landscape. PMID- 22088066 TI - The electronic spectrum of the previously unknown HAsO transient molecule. AB - The A(1)A('')-X(1)A(') electronic spectrum of the jet-cooled transient molecule HAsO and its deuterated isotopologue has been observed for the first time by pulsed discharge jet laser spectroscopy. The techniques of laser-induced fluorescence and single vibronic level emission were employed to probe the electronic properties of the species. The bending and AsO stretching frequencies have been determined in both states. A rotational analysis of the 0(0)(0) bands of both HAsO and DAsO has been completed and the following effective (r(0)) structures were derived: r(")(HAs) = 1.576(3) A, r(")(AsO) = 1.8342(5) A, and theta(") = 101.5(4) degrees ; and r(')(HAs) = 1.569(4) A, r(')(AsO) = 1.7509(9) A, and theta(') = 93.1(10) degrees . In the rotational analysis, lines induced by axis-tilting were observed, and calculated spectra with an axis tilting angle of 3.0(5) degrees reproduced the intensity of these lines. The change in geometry on electronic excitation is similar to that observed for the molecule HPO, with an increase in the X-O bond length and a decrease in the HXO angle, but contrary to the predictions of the Walsh diagram for generic HAB triatomic molecules. Our ab initio calculations show that the correlation between orbital energy and bond angle changes upon electronic excitation, resulting in the atypical angle change. PMID- 22088067 TI - Photoelectron spectroscopy of higher bromine and iodine oxide anions: electron affinities and electronic structures of BrO(2,3) and IO(2-4) radicals. AB - This report details a photoelectron spectroscopy (PES) and theoretical investigation of electron affinities (EAs) and electronic structures of several atmospherically relevant higher bromine and iodine oxide molecules in the gas phase. PES spectra of BrO(2)(-) and IO(2)(-) were recorded at 12 K and four photon energies--355 nm/3.496 eV, 266 nm/4.661 eV, 193 nm/6.424 eV, and 157 nm/7.867 eV--while BrO(3)(-), IO(3)(-), and IO(4)(-) were only studied at 193 and 157 nm due to their expected high electron binding energies. Spectral features corresponding to transitions from the anionic ground state to the ground and excited states of the neutral are unraveled and resolved for each species. The EAs of these bromine and iodine oxides are experimentally determined for the first time (except for IO(2)) to be 2.515 +/- 0.010 (BrO(2)), 2.575 +/- 0.010 (IO(2)), 4.60 +/- 0.05 (BrO(3)), 4.70 +/- 0.05 (IO(3)), and 6.05 +/- 0.05 eV (IO(4)). Three low-lying excited states along with their respective excitation energies are obtained for BrO(2) [1.69 (A (2)B(2)), 1.79 (B (2)A(1)), 1.99 eV (C (2)A(2))], BrO(3) [0.7 (A (2)A(2)), 1.6 (B (2)E), 3.1 eV (C (2)E)], and IO(3) [0.60 (A (2)A(2)), 1.20 (B (2)E), ~3.0 eV (C (2)E)], whereas six excited states of IO(2) are determined along with their respective excitation energies of 1.63 (A (2)B(2)), 1.73 (B (2)A(1)), 1.83 (C (2)A(2)), 4.23 (D (2)A(1)), 4.63 (E (2)B(2)), and 5.23 eV (F (2)B(1)). Periodate (IO(4)(-)) possesses a very high electron binding energy. Only one excited state feature with 0.95 eV excitation energy is shown in the 157 nm spectrum. Accompanying theoretical calculations reveal structural changes from the anions to the neutrals, and the calculated EAs are in good agreement with experimentally determined values. Franck-Condon factors simulations nicely reproduce the observed vibrational progressions for BrO(2) and IO(2). The low-lying excited state information is compared with theoretical calculations and discussed with their atmospheric implications. PMID- 22088068 TI - Kinetics of the reaction of the heaviest hydrogen atom with H2, the 4HeMU + H2 -> 4HeMUH + H reaction: experiments, accurate quantal calculations, and variational transition state theory, including kinetic isotope effects for a factor of 36.1 in isotopic mass. AB - The neutral muonic helium atom (4)HeMU, in which one of the electrons of He is replaced by a negative muon, may be effectively regarded as the heaviest isotope of the hydrogen atom, with a mass of 4.115 amu. We report details of the first muon spin rotation (MUSR) measurements of the chemical reaction rate constant of (4)HeMU with molecular hydrogen, (4)HeMU + H(2) -> (4)HeMUH + H, at temperatures of 295.5, 405, and 500 K, as well as a MUSR measurement of the hyperfine coupling constant of muonic He at high pressures. The experimental rate constants, k(HeMU), are compared with the predictions of accurate quantum mechanical (QM) dynamics calculations carried out on a well converged Born-Huang (BH) potential energy surface, based on complete configuration interaction calculations and including a Born-Oppenheimer diagonal correction. At the two highest measured temperatures the agreement between the quantum theory and experiment is good to excellent, well within experimental uncertainties that include an estimate of possible systematic error, but at 295.5 K the quantum calculations for k(HeMU) are below the experimental value by 2.1 times the experimental uncertainty estimates. Possible reasons for this discrepancy are discussed. Variational transition state theory calculations with multidimensional tunneling have also been carried out for k(HeMU) on the BH surface, and they agree with the accurate QM rate constants to within 30% over a wider temperature range of 200-1000 K. Comparisons between theory and experiment are also presented for the rate constants for both the D + H(2) and Mu + H(2) reactions in a novel study of kinetic isotope effects for the H + H(2) reactions over a factor of 36.1 in isotopic mass of the atomic reactant. PMID- 22088069 TI - Thermodynamics of viscous flow and elasticity of glass forming liquids in the glass transition range. AB - The elastic moduli of glasses from different chemical systems, including oxide, chalcogenide, oxynitride, and metallic, were investigated through the glass transition (T(g)), typically from 0.4 to 1.3 T(g). These data were used to interpret the temperature sensitivity of the shear viscosity coefficient obtained on the same materials. The relevant Gibbs free activation energy was estimated from the apparent heat of flow by means of the temperature dependence of the shear elastic modulus. The activation entropy associated with the viscous flow was also derived and was found to correlate with the fragile versus strong character of the glass forming liquids. Finally, the physicochemistry of the flow process was described on the basis of the glass network de-structuration which shows up through the temperature dependence of Poisson's ratio, and an expression for the shear viscosity coefficient is proposed which is chiefly based on the high temperature elastic behavior. PMID- 22088070 TI - Solution on the Bethe lattice of a hard core athermal gas with two kinds of particles. AB - Athermal lattice gases of particles with first neighbor exclusion have been studied for a long time as simple models exhibiting a fluid-solid transition. At low concentration the particles occupy randomly both sublattices, but as the concentration is increased one of the sublattices is occupied preferentially. Here, we study a mixed lattice gas with excluded volume interactions only in the grand-canonical formalism with two kinds of particles: small ones, which occupy a single lattice site and large ones, which, when placed on a site, do not allow other particles to occupy its first neighbors also. We solve the model on a Bethe lattice of arbitrary coordination number q. In the parameter space defined by the activities of both particles, at low values of the activity of small particles (z(1)) we find a continuous transition from the fluid to the solid phase as the activity of large particles (z(2)) is increased. At higher values of z(1) the transition becomes discontinuous, both regimes are separated by a tricritical point. The critical line has a negative slope at z(1) = 0 and displays a minimum before reaching the tricritical point, so that a re-entrant behavior is observed for constant values of z(2) in the region of low density of small particles. The isobaric curves of the total density of particles as a function of the density or the activity of small particles show a minimum in the fluid phase. PMID- 22088071 TI - Characteristics of Raman spectra for graphene oxide from ab initio simulations. AB - The Raman spectra of several locally stable structures of the graphene oxide (GO) have been simulated by ab initio calculations. Compared to graphite, the G band of GO is broadened and blueshifted due to the emergence of a series of new Raman peaks. The Raman intensities and positions of the D and G bands depend sensitively on the local atomic configurations. In addition to the normal epoxy and hydroxyl groups, other oxidation groups such as epoxy pairs are also studied. Epoxy pairs induce large blueshift of G band with respect to that of the graphite. PMID- 22088072 TI - How nanoscale seed particles affect vapor-liquid nucleation. AB - In this work, we used constrained lattice density functional theory to investigate how nanoscale seed particles affect heterogeneous vapor-liquid nucleation. The effects of the physical properties of nanoscale seed particles, including the seed size, the strength of seed-fluid attraction, and the shape of the seeds, on the structure of critical nuclei and nucleation barrier were systemically investigated. PMID- 22088073 TI - Monte Carlo simulation strategies for computing the wetting properties of fluids at geometrically rough surfaces. AB - We introduce Monte Carlo simulation methods for determining the wetting properties of model systems at geometrically rough interfaces. The techniques described here enable one to calculate the macroscopic contact angle of a droplet that organizes in one of the three wetting states commonly observed for fluids at geometrically rough surfaces: the Cassie, Wenzel, and impregnation states. We adopt an interface potential approach in which the wetting properties of a system are related to the surface density dependence of the surface excess free energy of a thin liquid film in contact with the substrate. We first describe challenges and inefficiencies encountered when implementing a direct version of this approach to compute the properties of fluids at rough surfaces. Next, we detail a series of convenient thermodynamic paths that enable one to obtain free energy information at relevant surface densities over a wide range of temperatures and substrate strengths in an efficient manner. We then show how this information is assembled to construct complete wetting diagrams at a temperature of interest. The strategy pursued within this work is general and is expected to be applicable to a wide range of molecular systems. To demonstrate the utility of the approach, we present results for a Lennard-Jones fluid in contact with a substrate containing rectangular-shaped grooves characterized by feature sizes of order ten fluid diameters. For this particular fluid-substrate combination, we find that the macroscopic theories of Cassie and Wenzel provide a reasonable description of simulation data. PMID- 22088074 TI - Switching and rectification of a single light-sensitive diarylethene molecule sandwiched between graphene nanoribbons. AB - The "open" and "closed" isomers of the diarylethene molecule that can be converted between each other upon photo-excitation are found to have drastically different current-voltage characteristics when sandwiched between two graphene nanoribbons (GNRs). More importantly, when one GNR is metallic and another one is semiconducting, strong rectification behavior of the "closed" diarylethene isomer with the rectification ratio >10(3) is observed. The surprisingly high rectification ratio originates from the band gap of GNR and the bias-dependent variation of the lowest unoccupied molecular orbital of the diarylethene molecule, the combination of which completely shuts off the current at positive biases. Results presented in this paper may form the basis for a new class of molecular electronic devices. PMID- 22088075 TI - Conformation and diffusion behavior of ring polymers in solution: a comparison between molecular dynamics, multiparticle collision dynamics, and lattice Boltzmann simulations. AB - We have studied the effect of chain topology on the structural properties and diffusion of polymers in a dilute solution in a good solvent. Specifically, we have used three different simulation techniques to compare the chain size and diffusion coefficient of linear and ring polymers in solution. The polymer chain is modeled using a bead-spring representation. The solvent is modeled using three different techniques: molecular dynamics (MD) simulations with a particulate solvent in which hydrodynamic interactions are accounted through the intermolecular interactions, multiparticle collision dynamics (MPCD) with a point particle solvent which has stochastic interactions with the polymer, and the lattice Boltzmann method in which the polymer chains are coupled to the lattice fluid through friction. Our results show that the three methods give quantitatively similar results for the effect of chain topology on the conformation and diffusion behavior of the polymer chain in a good solvent. The ratio of diffusivities of ring and linear polymers is observed to be close to that predicted by perturbation calculations based on the Kirkwood hydrodynamic theory. PMID- 22088076 TI - Structure and transport properties of polymer grafted nanoparticles. AB - We perform molecular dynamics simulations on a bead-spring model of pure polymer grafted nanoparticles (PGNs) and of a blend of PGNs with a polymer melt to investigate the correlation between PGN design parameters (such as particle core concentration, polymer grafting density, and polymer length) and properties, such as microstructure, particle mobility, and viscous response. Constant strain-rate simulations were carried out to calculate viscosities and a constant-stress ensemble was used to calculate yield stresses. The PGN systems are found to have less structural order, lower viscosity, and faster diffusivity with increasing length of the grafted chains for a given core concentration or grafting density. Decreasing grafting density causes depletion effects associated with the chains leading to close contacts between some particle cores. All systems were found to shear thin, with the pure PGN systems shear thinning more than the blend; also, the pure systems exhibited a clear yielding behavior that was absent in the blend. Regarding the mechanism of shear thinning at the high shear rates examined, it was found that the shear-induced decrease of Brownian stresses and increase in chain alignment, both correlate with the reduction of viscosity in the system with the latter being more dominant. A coupling between Brownian stresses and chain alignment was also observed wherein the non-equilibrium particle distribution itself promotes chain alignment in the direction of shear. PMID- 22088077 TI - Dissipative particle dynamics simulations of polymer-protected nanoparticle self assembly. AB - Dissipative particle dynamics simulations were used to study the effects of mixing time, solute solubility, solute and diblock copolymer concentrations, and copolymer block length on the rapid coprecipitation of polymer-protected nanoparticles. The simulations were aimed at modeling Flash NanoPrecipitation, a process in which hydrophobic solutes and amphiphilic block copolymers are dissolved in a water-miscible organic solvent and then rapidly mixed with water to produce composite nanoparticles. A previously developed model by Spaeth et al. [J. Chem. Phys. 134, 164902 (2011)] was used. The model was parameterized to reproduce equilibrium and transport properties of the solvent, hydrophobic solute, and diblock copolymer. Anti-solvent mixing was modeled using time dependent solvent-solute and solvent-copolymer interactions. We find that particle size increases with mixing time, due to the difference in solute and polymer solubilities. Increasing the solubility of the solute leads to larger nanoparticles for unfavorable solute-polymer interactions and to smaller nanoparticles for favorable solute-polymer interactions. A decrease in overall solute and polymer concentration produces smaller nanoparticles, because the difference in the diffusion coefficients of a single polymer and of larger clusters becomes more important to their relative rates of collisions under more dilute conditions. An increase in the solute-polymer ratio produces larger nanoparticles, since a collection of large particles has less surface area than a collection of small particles with the same total volume. An increase in the hydrophilic block length of the polymer leads to smaller nanoparticles, due to an enhanced ability of each polymer to shield the nanoparticle core. For unfavorable solute-polymer interactions, the nanoparticle size increases with hydrophobic block length. However, for favorable solute-polymer interactions, nanoparticle size exhibits a local minimum with respect to the hydrophobic block length. Our results provide insights on ways in which experimentally controllable parameters of the Flash NanoPrecipitation process can be used to influence aggregate size and composition during self-assembly. PMID- 22088078 TI - Detailed balance condition and effective free energy in the primitive chain network model. AB - We consider statistical mechanical properties of the primitive chain network (PCN) model for entangled polymers from its dynamic equations. We show that the dynamic equation for the segment number of the PCN model does not reduce to the standard Langevin equation which satisfies the detailed balance condition. We propose heuristic modifications for the PCN dynamic equation for the segment number, to make it reduce to the standard Langevin equation. We analyse some equilibrium statistical properties of the modified PCN model, by using the effective free energy obtained from the modified PCN dynamic equations. The PCN effective free energy can be interpreted as the sum of the ideal Gaussian chain free energy and the repulsive interaction energy between slip-links. By using the single chain approximation, we calculate several distribution functions of the PCN model. The obtained distribution functions are qualitatively different from ones for the simple slip-link model without any direct interactions between slip links. PMID- 22088079 TI - Thermal conductivity of carbon nanotube-polyamide-6,6 nanocomposites: reverse non equilibrium molecular dynamics simulations. AB - The thermal conductivity of composites of carbon nanotubes and polyamide-6,6 has been investigated using reverse non-equilibrium molecular dynamics simulations in a full atomistic resolution. It is found, in line with experiments, that the composites have thermal conductivities, which are only moderately larger than that of pure polyamide. The composite conductivities are orders of magnitude less than what would be expected from naive additivity arguments. This means that the intrinsic thermal conductivities of isolated nanotubes, which exceed the best conducting metals, cannot be harnessed for heat transport, when the nanotubes are embedded in a polymer matrix. The main reason is the high interfacial thermal resistance between the nanotubes and the polymer, which was calculated in addition to the total composite thermal conductivity as well as that of the subsystem. It hinders heat to be transferred from the slow-conducting polymer into the fast-conducting nanotubes and back into the polymer. This interpretation is in line with the majority of recent simulation works. An alternative explanation, namely, the damping of the long-wavelength phonons in nanotubes by the polymer matrix is not supported by the present calculations. These modes provide most of the polymers heat conduction. An additional minor effect is caused by the anisotropic structure of the polymer phase induced by the nearby nanotube surfaces. The thermal conductivity of the polymer matrix increases slightly in the direction parallel to the nanotubes, whereas it decreases perpendicular to it. PMID- 22088080 TI - Monte Carlo simulation studies of ring polymers at athermal and theta conditions. AB - By use of an intramolecular criterion, i.e., the direct proportionality between mean square dimension and chain length, theta conditions for linear chains and ring shaped polymers are evaluated for several types of cubic lattice chains (simple cubic, body centered cubic, and face centered cubic). The properties of the rings are evaluated for the same thermodynamic conditions under which they are prepared thus allowing for a natural amount of knots which have been identified by use of Alexander polynomials. For the limit of infinite chain lengths the same theta parameter is found for linear chains and rings. On the contrary, a significant theta point depression occurs due to an additional excluded volume effect if unknots are exclusively regarded. Parameters characteristic of the shape of rings and chains under theta conditions extrapolated to infinite chain length fairly well coincide with respective data for random walks. Mean square dimensions (characteristic of the size) of theta systems are slightly in excess as compared to nonreversal random walks due to the necessity of avoiding overlaps on a local scale. Furthermore athermal systems are studied as well for comparison; mean square dimensions are described by use of scaling relations with proper short chain corrections, shape parameters are given in the limit of infinite chain length. PMID- 22088081 TI - Potential of mean force between a large solute and a biomolecular complex: a model analysis on protein flux through chaperonin system. AB - Insertion of a large solute into an even larger vessel comprising biopolymers followed by release of the same solute from it is one of the important functions sustaining life. As a typical example, an unfolded protein is inserted into a chaperonin from bulk aqueous solution, a cochaperonin acting as a lid is attached to the chaperonin rim and the protein folds into its native structure within the closed cavity, the cochaperonin is detached after the folding is finished, and the folded protein is released back to the bulk solution. On the basis of the experimental observations manifesting that the basic aspects of the protein flux through the chaperonin system is independent of the chaperonin, cochaperonin, and protein species, we adopt a simple model system with which we can cover the whole cycle of the protein flux. We calculate the spatial distribution of the solvent mediated potential of mean force (PMF) between a spherical solute and a cylindrical vessel or vessel/lid complex. The calculation is performed using the three-dimensional integral equation theory, and the PMF is decomposed into energetic and entropic components. We argue that an unfolded protein with a larger excluded volume (EV) and weak hydrophobicity is entropically inserted into the chaperonin cavity and constrained within a small space almost in its center. The switch from insertion to release is achieved by decreasing the EV and turning the protein surface hydrophilic in the folding process. For this release, in which the energetic component is a requisite, the feature that the chaperonin inner surface in the absence of the cochaperonin is not hydrophilic plays essential roles. On the other hand, the inner surface of the chaperonin/cochaperonin complex is hydrophilic, and the protein is energetically repelled from it: The protein remains constrained within the small space mentioned above without contacting the inner surface for correct folding. The structural and inner-surface properties of the chaperonin or complex are controlled by the adenosine triphosphate (ATP) binding to the chaperonin, hydrolysis of ATP into adenosine diphosphate (ADP) and Pi, and dissociation of ADP and Pi. The function of the chaperonin system is exhibited by synchronizing the chemical cycle of ATP hydrolysis with hydration properties of a protein in the water confined on the scale of a nanometer which are substantially different from those in the bulk water. PMID- 22088083 TI - Retraction: "Multidimensional spatial-spectral holographic interpretation of NMR photography" [J. Chem. Phys. 124, 194108 (2006)]. PMID- 22088082 TI - Note: scale-free center-of-mass displacement correlations in polymer films without topological constraints and momentum conservation. PMID- 22088085 TI - Development and characterization of microsatellite markers from tropical forage Stylosanthes species and analysis of genetic variability and cross-species transferability. AB - A limited number of functional molecular markers has slowed the desired genetic improvement of Stylosanthes species. Hence, in an attempt to develop simple sequence repeat (SSR) markers, genomic libraries from Stylosanthes seabrana B.L. Maass & 't Mannetje (2n=2x=20) using 5' anchored degenerate microsatellite primers were constructed. Of the 76 new microsatellites, 21 functional primer pairs were designed. Because of the small number of primer pairs designed, 428 expressed sequence tag (EST) sequences from seven Stylosanthes species were also examined for SSR detection. Approximately 10% of sequences delivered functional primer pairs, and after redundancy elimination, 57 microsatellite repeats were selected. Tetranucleotides followed by trinucleotides were the major repeated sequences in Stylosanthes ESTs. In total, a robust set of 21 genomic-SSR (gSSR) and 20 EST-SSR (eSSR) markers were developed. These markers were analyzed for intraspecific diversity within 20 S. seabrana accessions and for their cross species transferability. Mean expected (He) and observed (Ho) heterozygosity values with gSSR markers were 0.64 and 0.372, respectively, whereas with eSSR markers these were 0.297 and 0.214, respectively. Dendrograms having moderate bootstrap value (23%-94%) were able to distinguish all accessions of S. seabrana with gSSR markers, whereas eSSR markers showed 100% similarities between few accessions. The set of 21 gSSRs, from S. seabrana, and 20 eSSRs, from selected Stylosanthes species, with their high cross-species transferability (45% with gSSRs, 86% with eSSRs) will facilitate genetic improvement of Stylosanthes species globally. PMID- 22088086 TI - Xanthohumol uptake and intracellular kinetics in hepatocytes, hepatic stellate cells, and intestinal cells. AB - Xanthohumol (XN) is the major prenylated chalcone of hops and hence an ingredient of beer. Despite many advances in understanding of the pharmacology of XN, one largely unresolved issue is its low bioavailability in the human organism. Also, not much is known about its actual concentrations and pharmacokinetics in liver and intestinal cells. Therefore, the uptake, intracellular distribution, and kinetics of XN were studied in various cell types, namely, hepatocellular carcinoma cells (HuH-7), hepatic stellate cells (HSC), primary cultured hepatocytes, and colorectal adenocarcinoma cells (Caco-2). Fluorescent microscopy allowed for the first time visualization and tracing of the uptake and intracellular distribution of XN. A rapid accumulation of XN concentrations that were up to >60-fold higher than the concentration present in the ambient culture medium was observed. Fluorescence recovery after photobleaching experiments revealed that most XN molecules are bound to cellular proteins, which may alter properties of cellular factors. PMID- 22088091 TI - Short term supplementation of dietary antioxidants selectively regulates the inflammatory responses during early cutaneous wound healing in diabetic mice. AB - BACKGROUND: Diabetic foot ulcers are serious complications for diabetic patients, yet the precise mechanism that underlines the treatment of these diabetic complications remains unclear. We hypothesized that dietary antioxidant supplementation with vitamin C, combined either with vitamin E or with vitamin E and NAC, improves delayed wound healing through modulation of blood glucose levels, oxidative stress, and inflammatory response. METHODS: Diabetes was induced by administration of alloxan monohydrate. Mice were divided into 4 groups; CON (non-diabetic control mice fed AIN 93 G purified rodent diet), DM (diabetic mice fed AIN 93 G purified rodent diet), VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet), and Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E, and 2.5% NAC supplemented diet). After 10 days of dietary antioxidant supplementation, cutaneous full-thickness excisional wounds were performed, and the rate of wound closure was examined. TBARS as lipid peroxidation products and vitamin E levels were measured in the liver. Expression levels of oxidative stress and inflammatory response related proteins were measured in the cutaneous wound site. RESULTS: Dietary antioxidant supplementation improved blood glucose levels and wound closure rate and increased liver vitamin E, but not liver TBARS levels in the diabetic mice as compared to those of the CON. In addition, dietary antioxidant supplementation modulated the expression levels of pIkappaBalpha, HO-1, CuZnSOD, iNOS and COX-2 proteins in the diabetic mice. CONCLUSIONS: These findings demonstrated that delayed wound healing is associated with an inflammatory response induced by hyperglycaemia, and suggests that dietary antioxidant supplementation may have beneficial effects on wound healing through selective modulation of blood glucose levels, oxidative stress, and inflammatory response. PMID- 22088092 TI - A new genus and a new species of Cladorchiidae (Digenea: Dadayiinae) from Podocnemis expansa (Chelonia) of the neotropical region, State of Para, Brazil. AB - A new species of amphistome digenean from the stomach and intestine of Podocnemis expansa (Pelomedusidae), of the tropical rain forest, from the State of Para, Brazil, is described and allocated to a new genus ( Oriximinatrema noronhae ). The new species is characterized by the presence of an esophageal bulb, an esophageal extension uncovered by an extension of the pharyngeal sacs, a well developed cirrus sac, post-bifurcal genital sucker, a ventro-terminal acetabulum with an anterior lip, and medium-sized eggs. This is the first report of a Dadayiinae trematode infecting a reptilian host. PMID- 22088093 TI - Bionano donor-acceptor hybrids of porphyrin, ssDNA, and semiconductive single wall carbon nanotubes for electron transfer via porphyrin excitation. AB - Photoinduced electron transfer in self-assemblies of porphyrins ion-paired with ssDNA wrapped around single-wall carbon nanotubes (SWCNTs) has been reported. To accomplish the three-component hybrids, two kinds of diameter-sorted semiconducting SWCNT(n,m)s of different diameter ((n,m) = (6,5) and (7,6)) and free-base or zinc porphyrin bearing peripheral positive charges ((TMPyP(+))M (tetrakis(4-N-methylpyridyl)porphyrin); M = Zn and H(2)) serving as light absorbing photoactive materials are utilized. The donor-acceptor hybrids are held by ion-pairing between the negatively charged phosphate groups of ssDNA on the surface of the SWCNT and the positively charged at the ring periphery porphyrin macrocycle. The newly assembled bionano donor-acceptor hybrids have been characterized by transmission electron microscopy (TEM) and spectroscopic methods. Photoinduced electron transfer from the excited singlet porphyrin to the SWCNTs directly and/or via ssDNA as an electron mediator has been established by performing systematic studies involving the steady-state and time-resolved emission as well as the transient absorption studies. Higher charge-separation efficiency has been successfully demonstrated by the selection of the appropriate semiconductive SWCNTs with the right band gap, in addition to the aid of ssDNA as the electron mediator. PMID- 22088094 TI - Integrity of chromatin and replicating DNA in nuclei released from fission yeast by semi-automated grinding in liquid nitrogen. AB - BACKGROUND: Studies of nuclear function in many organisms, especially those with tough cell walls, are limited by lack of availability of simple, economical methods for large-scale preparation of clean, undamaged nuclei. FINDINGS: Here we present a useful method for nuclear isolation from the important model organism, the fission yeast, Schizosaccharomyces pombe. To preserve in vivo molecular configurations, we flash-froze the yeast cells in liquid nitrogen. Then we broke their tough cell walls, without damaging their nuclei, by grinding in a precision controlled motorized mortar-and-pestle apparatus. The cryo-ground cells were resuspended and thawed in a buffer designed to preserve nuclear morphology, and the nuclei were enriched by differential centrifugation. The washed nuclei were free from contaminating nucleases and have proven well-suited as starting material for genome-wide chromatin analysis and for preparation of fragile DNA replication intermediates. CONCLUSIONS: We have developed a simple, reproducible, economical procedure for large-scale preparation of endogenous-nuclease-free, morphologically intact nuclei from fission yeast. With appropriate modifications, this procedure may well prove useful for isolation of nuclei from other organisms with, or without, tough cell walls. PMID- 22088095 TI - Microbial production of hyaluronic acid: current state, challenges, and perspectives. AB - Hyaluronic acid (HA) is a natural and linear polymer composed of repeating disaccharide units of beta-1, 3-N-acetyl glucosamine and beta-1, 4-glucuronic acid with a molecular weight up to 6 million Daltons. With excellent viscoelasticity, high moisture retention capacity, and high biocompatibility, HA finds a wide-range of applications in medicine, cosmetics, and nutraceuticals.Traditionally HA was extracted from rooster combs, and now it is mainly produced via streptococcal fermentation. Recently the production of HA via recombinant systems has received increasing interest due to the avoidance of potential toxins. This work summarizes the research history and current commercial market of HA, and then deeply analyzes the current state of microbial production of HA by Streptococcus zooepidemicus and recombinant systems, and finally discusses the challenges facing microbial HA production and proposes several research outlines to meet the challenges. PMID- 22088096 TI - Development of the enantioselective addition of ethyl diazoacetate to aldehydes: asymmetric synthesis of 1,2-diols. AB - A novel synthetic strategy toward the asymmetric synthesis of vicinal diols bearing a tertiary center is presented. The method encompasses the dinuclear Mg catalyzed asymmetric addition of ethyl diazoacetate into several aldehydes, oxidation of the diazo functionality, and diastereoselective alkyl transfer of various organometallics into the resulting chiral beta-hydroxy-alpha-ketoesters to afford a diverse range of 1,2-diols in high yield, diastereoselectivity, and chirality transfer. PMID- 22088097 TI - Urinary albumin-to-creatinine ratio in a first-morning void urine and prehypertension among Chinese Han women. AB - BACKGROUND: This study was operated to investigate the association between urinary albumin-to-creatinine ratio (ACR) and prehypertension among Chinese Han women. METHODS: Information on blood pressure measurement and other variables were obtained, and blood and urine samples collected in 1796 women aged >=30 years. The association between urinary ACR and prehypertension were analyzed by using multivariate non-conditional logistic regression models. RESULTS: Average urinary ACR was higher in hypertensives than in prehypertensives (median: 15.54 vs 9.01 mg/g), and in prehypertensives than in normotensives (median: 9.01 vs 7.13 mg/g). Both systolic and diastolic blood pressures increased with urinary ACR. Compared with the lowest quartile of urinary ACR, multivariate adjusted odds ratios of prehypertension were 1.25 (95% confidence interval, 0.89-1.78), 1.95 (1.30-2.92) and 1.59 (1.02-2.48) for the second, third and fourth quartiles, respectively. After exclusion of subjects with diabetes or use of antihypertensive medication, the odds ratio of prehypertension still increased with urinary ACR levels. CONCLUSION: Increased urinary ACR was significantly and positively associated with prehypertension among Chinese Han women. PMID- 22088098 TI - Absolute monocyte count identifies high-risk patients with lymphomas: "absolutely" simple and "counts" mean a lot! PMID- 22088099 TI - Variant genotypes of MDR1 C3435T increase the risk of leukemia: evidence from 10 case-control studies. AB - The C3435T (Ile1142Ile) polymorphism of the multidrug resistance gene (MDR1) has been implicated in leukemia risk, but the reported results are inconsistent. Here we performed a meta-analysis to evaluate the association between C3435T polymorphism and the risk of leukemia using all case-control studies published before June 2011 according to PubMed. A total of 10 case-control studies were included in this analysis. We found that variant genotypes of C3435T (CT/TT) were significantly associated with an increased risk of leukemia (CT/TT vs. CC: odds ratio [OR] = 1.29; 95% confidence interval [CI] = 1.11-1.50, p = 0.284 for heterogeneity test). Additionally, the association was more significant in chronic leukemia (specifically B-cell chronic lymphocytic leukemia [B-CLL]) (OR = 1.94; 95% CI = 1.32-2.85, p = 0.648 for heterogeneity test) than in acute leukemia (OR = 1.19; 95% CI = 1.01-1.40, p = 0.616 for heterogeneity test), p = 0.021 for heterogeneity test between groups. These findings provide further evidence that the MDR1 C3435T variant may modify the susceptibility to leukemia. PMID- 22088100 TI - Rapid and specific influenza virus detection by functionalized magnetic nanoparticles and mass spectrometry. AB - BACKGROUND: The timely and accurate diagnosis of specific influenza virus strains is crucial to effective prophylaxis, vaccine preparation and early antiviral therapy. The detection of influenza A viruses is mainly accomplished using polymerase chain reaction (PCR) techniques or antibody-based assays. In conjugation with the immunoassay utilizing monoclonal antibody, mass spectrometry is an alternative to identify proteins derived from a target influenza virus. Taking advantage of the large surface area-to-volume ratio, antibody-conjugated magnetic nanoparticles can act as an effective probe to extract influenza virus for sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and on bead mass spectrometric analysis. RESULTS: Iron oxide magnetic nanoparticles (MNP) were functionalized with H5N2 viral antibodies targeting the hemagglutinin protein and capped with methoxy-terminated ethylene glycol to suppress nonspecific binding. The antibody-conjugated MNPs possessed a high specificity to H5N2 virus without cross-reactivity with recombinant H5N1 viruses. The unambiguous identification of the captured hemagglutinin on magnetic nanoparticles was realized by SDS-PAGE visualization and peptide sequence identification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CONCLUSIONS: The assay combining efficient magnetic separation and MALDI-MS readout offers a rapid and sensitive method for virus screening. Direct on-MNP detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) provided high sensitivity (~10(3) EID(50) per mL) and a timely diagnosis within one hour. The magnetic nanoparticles encapsulated with monoclonal antibodies could be used as a specific probe to distinguish different subtypes of influenza. PMID- 22088102 TI - Preface. PMID- 22088101 TI - Updates on the treatment of essential hypertension: a summary of AHRQ's comparative effectiveness review of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and direct renin inhibitors. AB - BACKGROUND: In 2007, the Agency for Healthcare Research and Quality (AHRQ) published a comparative effectiveness review (CER) on the benefits and risks of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) for treating essential hypertension in adults. The main findings indicated that the 2 classes of antihypertensive medications caused similar reductions in blood pressure, although higher rates of adverse events, especially cough, were reported by patients treated with ACEIs. In addition, the 2007 review indicated no treatment related differences in lipid levels, glycemic control, or progression of kidney disease among the agents. Since 2007, 39 relevant studies have been published that compare outcomes for adults treated with ACEIs versus ARBs or a drug in one of these 2 classes versus a direct renin inhibitor (DRI). To systematically analyze findings from the new research, AHRQ commissioned and, in June 2011, published an updated comparative effectiveness review on the benefits and risks of agents that target the renin-angiotensin- aldosterone system (RAAS), specifically ACEIs, ARBs, and DRIs. OBJECTIVES: To (a) familiarize health care professionals with the methods and findings from AHRQ's 2011 comparative effectiveness review on ACEIs, ARBs, and DRIs for adults with essential hypertension; (b) provide commentary and encourage consideration of the clinical and managed care applications of the review findings; and (c) identify limitations to the existing research on the benefits and risks of ACEIs, ARBs, and DRIs. SUMMARY: Consistent with the findings from AHRQ's 2007 report, the 2011 update indicated no overall differences in blood pressure control, mortality rates, and major cardiovascular events in patients treated with ACEIs versus ARBs. With a low strength of evidence, 2 studies reported a small significantly greater blood pressure reduction for patients treated with the DRI aliskiren versus the ACEI ramipril. Studies evaluating the DRI aliskiren versus ACEIs and ARBs on mortality and morbidity outcomes were relatively short, and few deaths or cardiovascular events occurred, resulting in insufficient evidence to discern differences. A random-effects meta-analysis of 23 RCTs comparing ACEIs and ARBs found no significant difference in the proportion of patients who achieved successful blood pressure control on a single antihypertensive agent. Compared with ARBs and the DRI aliskiren, ACEIs were consistently associated with higher rates of cough. Withdrawals due to adverse events were modestly more frequent for patients receiving ACEI rather than ARBs or DRIs; this is consistent with the differential rates of cough. There was no evidence of differential effects of ACEIs, ARBs, or DRIs on the outcomes of lipids, renal outcomes, carbohydrate metabolism or diabetes, or left ventricular mass; however, there was not a high strength of evidence for any of these outcomes. Regarding the question of whether ACEIs, ARBs, or DRIs are associated with better outcomes in specific patient subgroups, the evidence was insufficient to reach firm conclusions. PMID- 22088103 TI - Stabile Isotope in den Interaktionen von Parasiten und Wirten bei Hoheren Pflanzen. AB - Abstract An overview is given about the delta(13)C- and delta5D-values in the organic material of hemi- and full- parasitic higher plants and of their hosts. Hemiparasites have to direct the content of the host xylem into their tissues by lowering their water potential. They achieve this by active water secretion or by lowering the stomatal resistance. In the latter case, the intercellular CO(2) concentration in the chlorenchyme of the parasite is increased. This causes a reduction of the (13)C-content (delta(13)C-value of the parasite more negative than of the host). The dry matter of the mistletoes is always richer in deuterium than that of the host. The reason for this fact is unknown. In the case hemiparasites and their hosts show differences in the (13)CO(2)-discrimination during the photosynthetic CO(2)-fixation, an eventual transfer of organic material from host to parasite can be checked. By this way a holoparasitic mistletoe, Tristerix aphyllus, could be demonstrated. In contrast to mistletoes on C3-hosts, such on CAM-hosts have a lower deuterium content in the dry mass than the hosts. Holoparasites get all their organic material from the hosts and mirror, therefore, in their delta(13)C-values those of the hosts. Their deuterium content in the organic material is always higher than the one in the host. The reason is unknown. PMID- 22088104 TI - Uptake of [(15)N] Ammonium and [(15)N]Nitrate in a 140-Year-Old Spruce Stand (Picea abies) in the Fichtelgebirge (NE Bavaria). AB - Abstract In April 1994 a (15)N tracer pulse study was started in a 140-year-old spruce stand (Picea abies [L.] Karst.) located at the Fichtelgebirge (NE Bavaria). Highly enriched (98%) [(15)N]ammonium and [(15)N]nitrate were applied simulating wet deposition. For two growing seasons the pathways and dynamics of the tracer were followed in all compartments of spruce (needles and twigs of all age classes, stem wood and bark, roots) and understorey vegetation and in soils of the organic (L/Of and Oh) and mineral horizons (A(0-5) and A(5-10)). By variations of the application time on different plots within the growing season (spring, summer and autumn) a seasonal effect of labelling on uptake and distribution patterns was tested. First results of this tracer study indicate that young and old spruce stands do not differ basically in pattern of uptake and distribution of mineral nitrogen. There are indications that spruce uses preferentially ammonium versus nitrate and that the ratio of ammonium/nitrate which is being consumed depends on the ammonium/nitrate ratio in the soil solution. The uptake rates decrease within the growing season. PMID- 22088105 TI - The Fate of [(15)N]Ammonium and [(15)N]Nitrate in the Soil of a 140-Year-Old Spruce Stand (Picea Abies) in the Fichtelgebirge (NE-Bavaria). AB - Abstract A (15)N tracer-experiment was carried out in a 140-year-old spruce stand (Picea abies (L.) Karst.) in the Fichtelgebirge (NE-Bavaria, Germany). Highly enriched (98 at%) [(15)N]ammonium and [(15)N]nitrate were applied as tracers by simulation of a deposition of 41.3 mol N ha(-1) with 11 water m(-2). To examine seasonal variations of uptake by spruce and understorey vegetation, different plots were labelled in spring, summer and autumn 1994. One aim of the present study was to perfect a method of preparation of soil extracts for isotope ratio mass spectrometry (IRMS) measurements. Ammonium and nitrate from soil extracts were prepared for IRMS measurements by steam distillation and subsequent freeze drying. Additionally, tracer distribution and transformations in the soil nitrogen pools were examined. Ammonium, nitrate and total nitrogen were examined in the organic layer and the upper 10 cm of the mineral soil during 3 months after the first tracer application in spring 1994. In July 1994, three months after tracer application, 40% of the [(15)N]ammonium label and 29% of the [(15)N]nitrate label, respectively, were recovered in the total N pool of the investigated soil horizons. In the organic layer the L/Of horizon retained most of the recovered tracers. Nitrification, immobilisation and mineralisation occurred even under the conditions of high soil acidity at the study site. PMID- 22088106 TI - Untersuchungen mit (15)n im dauerdungungsfeldversuch. AB - Abstract Long-term static fertilizer experiments are important for the soil fertility research, particular for using nitrogen problems. There are several possibilities for (15)N-traces in such experiments. One example is the International Organic Nitrogen Long-Term Experiment at Berlin-Dahlem in which (15)N-tracers are used, involving organic and inorganic fertilizers. By analyzing the soil and the plant biomass, it was possible to distinguish between nitrogen originating from the soil and that from the fertilizer. Some results are published. PMID- 22088107 TI - Course of uptake of weed-borne nitrogen by maize, tested with (15)n. AB - Abstract The course of uptake of weed-borne nitrogen by maize was tested with (15)N in a pot experiment with silty loam after common growth of maize and Chenopodium album L., and mulching the weed in the 5-leaf stage of maize. Harvests 4,8 and 12 weeks after mulching show that the maize took up 35, 63 and 70% of the weed-borne nitrogen, resp., in consequence of a rapid and almost complete mineralization. The portion of weed-borne nitrogen in total N of the maize was 16% at all harvest dates. The differences in yield between weeded and unweeded maize were not significant neither at 5-leaf stage nor at corn maturity. PMID- 22088108 TI - Nitrogen fixation and nitrogen fertilization of soybeans. AB - Abstract In pot experiments with (15)N labelled soil and mineral (15)N, the influence of Bradyrhizobium (Rhizobium japonicum) inoculation and N fertilization on the symbiotic N(2) fixation and yield of soybeans [Glycine max (L.) Merill., cv. 'Fiskeby V'] was investigated. Symbiotic N(2) fixation only occured after inoculation with Bradyrhizobium. Considerable differences in efficiency of the bacterial preparations were observed. Shortly after flowering, the symbiotic nitrogen fixation was finished and, subsequently, soybeans took up considerable N amounts from the soil. N fertilization at seeding suppressed N(2) fixation of soybeans. In this case, the dry matter and nitrogen yield increased, because the loss of fixed nitrogen was overcompensated by the mineral N uptake. During flowering of soybeans, the N(2) fixation was not affected by N supply, because this process was already terminated. The mineral N was additionally available to the plants and led to increased N amounts in plants. It was absorbed to a considerable degree by soybeans. The mineral N was translocated (partly, after intermediate storage in the vegetative organs) into the seeds thus increasing their yields. PMID- 22088109 TI - The impact of ozone on the (15)n incorporation and nitrogen assimilation of wheat and maize. AB - Abstract Young wheat (C3) and maize (C4) plants were exposed to near-ambient concentrations of ozone in open-top chambers in order to investigate the possible effects of ozone on nitrogen metabolism. Nitrogen was supplied to the plants by adding (15)N-labelled tracer substances via the soil substrate. Enzyme activities (NADH nitrate reductase, nitrite reductase, glutamine synthetase and NADH glutamate dehydrogenase) and the incorporation of (15)N were determined. The findings show that nitrogen metabolism was affected by O(3), however, there were distinct differences between the two species. In plants treated with O(3), NADH nitrate reductase activity in maize leaves was reduced, while NR activity in wheat leaves only slightly declined. Only minor changes were observed with respect to the activities of nitrite reductase, glutamine synthetase and NADH glutamate dehydrogenase. Feeding experiments using (15)NO(3) (-) showed that the incorporation of nitrate nitrogen in wheat plants exposed to ozone remains virtually unchanged, whereas in maize plants reduced incorporation rates were observed for nitrate nitrogen. The incorporation of ammonium nitrogen was distinctly increased in wheat and maize by the impact of ozone. When investigating pigment contents, reduced levels of chlorophyll a and b and carotenoids were observed, whereas the pigment content of wheat leaves remained unchanged. These results indicate that young maize plants are more susceptible than wheat plants to short-term ozone exposure. PMID- 22088110 TI - Prospects and limitations of an isotope tracer technique for understanding sulfur cycling in forested and agro-ecosystems. AB - Abstract Applications of isotopically distinct sulfur compounds have recently been used for tracing the fate of added sulfur in whole catchments or sub compartments therein. Basic principles, the analytical methodology, and data evaluation for this isotope tracer technique are briefly described. We recommend that delta(34)S-values of applied and natural sulfur compounds in the investigated ecosystem should differ by more than 200/00 in order to successfully ascertain sulfur fluxes. Where possible, a high ratio of applied sulfur loads versus sulfur pool sizes in the ecosystem should also be realized in order to allow the assessment of sulfur transformations in the study area. Prospects and limitations of this isotope tracer technique are critically discussed by reviewing results from recently or currently conducted lysimeter and field experiments. PMID- 22088111 TI - Sulfate Reduction in a Forested Catchment as Indicated by delta(34)S Values of Sulfate in Soil Solutions and Runoff. AB - Abstract In a forested catchment in the Fichtelgebirge mountains (NE-Bavaria, Germany) the long term SO(4) (2-) budget (average 1988-1994) indicated that about 40% of the input with throughfall (16.8 kg SO(4) (2-) S.ha(-1).yr(-1)) was retained in the catchment. In order to identify processes acting as potential SO(4) (2-) sinks, delta(34)S values of SO(4) (2-) in soil solutions and runoff were measured between May and November 1994. delta(34)S values of the runoff and the fen were higher (5.80/00) than the delta(34)S values of the soil solution of the oxic soils in the terrestrial area (3.90/00). Because there is no lithogenic S source within the catchment, it can be assumed that SO(4) (2-) deposition is the only S source in the catchment. Thus the results were interpreted as a result of SO(4) (2-) reduction within the catchment, because the uptake of (32)S is favoured during the dissimilatory SO(4) (2-) reduction and (34)S is consequently enriched in the soil solution. To estimate the amount of SO(4) (2-) reduced isotopic fractionation factors between - 90/00 and -460/00 were considered, resulting in SO(4) (2-) reduction rates of 1.8-9.3 kg SO(4) (2)-S.ha(-1)yr(-1). It was concluded that besides dissimilatory SO(4) (2-) reduction another sink exists in the catchment (e.g. SO(4) (2-) sorption in deep soil layers). PMID- 22088112 TI - Influence of earthworms on the sulfur turnover in the soil. AB - Abstract The effects of earthworm activity on the concentration and isotopic composition of total sulfur in soils was investigated using batch experiments. Two ecologically different lumbricid species, the anecic Lumbricus terrestris and the endogeic Aporrectodea caliginosa, were used. The earthworms were fed birch leaves, beech leaves, cattle manure or mixed plant litter. All food sources differed isotopically (delta(34)S) from the soil (Parabraunerde). As a reference, one experiment was carried out without additional food. The experimental results show, that both earthworm species influence the total S-content and the delta(34)S-values in the soil by digestion of the different food sources. The differences in the total S-content of the earthworm tissues and in the S-isotopic composition of the casts can be attributed to the ecological differences between the earthworm species. PMID- 22088115 TI - Compartmental approach for evaluation of plasma kinetics and (13)co(2)-exhalation after oral loading with L-[1-(13)c]leucine. AB - Abstract A seven compartment model was applied for evaluation of oral L-[1 (13)C]leucine loading tests (38 MUmol/kg body wt.) in healthy volunteers. The model comprises transport and absorption in stomach and gut into a central L leucine-compartment which is connected to a protein compartment and to the compartment of the corresponding 2-oxo acid. CO(2) release from the latter occurs in a fast and a slow compartment into the central CO(2) compartment for exhalation. Using the fmins routine of MATLAB for parameter estimation, a good agreement was obtained between calculated and actually measured kinetics of (13)C labelled metabolites and a mean in vivo L-leucine oxidation of 0.365 +/- 0.071 MUmol/kg per min (n = 5) was computed. Plausibility of the model was checked by predicting in vivo leucine oxidation rates from primed continuous infusion tests (priming: L-[1-(13)C]leucine, 5 MUmol/kg; NaH(13)CO(2), 1.2 MUmol/kg; infusion: L [1-(13)C]leucine, 5 MUmol/kg per h). In 5 tested volunteers, the experimental L leucine oxidation rate amounted to 0.358 +/- 0.105 MUmol/kg per min versus predicted 0.324+/-0.099 MUmol/kg per min. Possible causes for some observed intraindividual variations are discussed. PMID- 22088117 TI - Microcombustion of ng Amounts of Carbon in Non-Volatile Materials for isotope Ratio Evaluation. AB - Abstract A novel microcombustion technique for carbon isotopic analysis of nanogram amounts of carbon in non-volatile materials based on isotope ratio monitoring (irm) mass spectrometry is described. Liquid or solid samples placed in a quartz sleeve are combusted at 1000 degrees C in a continuous stream of helium and oxygen. CO(2) removed from the carrier gas stream by cryogenic trapping is transferred onto a GC column. Following GC separation, the CO(2) is transferred via an open split to the ion source of a gas isotope ratio mass spectrometer. Reproducibility for samples >25 nmol carbon is <10/00. Problems associated with blanks from various sources and with reproducible deposition of small sample amounts led to variable accuracy, which was dependent on the compound class being analysed. Minimum sample size was in the range from 5 to 10 nmol carbon. Measurements of dissolved organic carbon (DOC) of groundwater from Germany yielded consistent values of delta(13)C = -28.80/00. PMID- 22088118 TI - New methods for fully automated isotope ratio determination from hydrogen at the natural abundance level. AB - Abstract A variety of methods for measurement of (2)H/(1)H from H(2) are evaluated for their ability to be fully automated and for applicability to automated isotopic analysis of water and organic compounds. Equilibration of water with H(2) gas with the aid of a platinum catalyst has been commercialized into a fully automated sample preparation device. A second and newer technique, involving injecting water, methane, or other volatile organic compounds onto hot chromium in a reactor attached to the dual inlet system of a gas isotope ratio mass spectrometer, can be integrated with a conventional GC-autosampler to allow automated analysis of a variety of substrates. Both techniques result in precisions around 10/00 (delta notation) on the VSMOW scale, and are fast and accurate, and with appropriate mass spectrometers require only negligible scaling for the SLAP/VSMOW difference. Several experimental methods which show considerable promise employ "isotope ratio monitoring" (irm) inlet systems, in which a carrier gas is used for transport of H(2) to the mass spectrometer. Any such method has to address the problem of He ions corrupting the measurement of the H(2) ions. One such approach uses a heated palladium membrane for selective introduction of H(2) into the mass spectrometer, and a second involves modifications to the ion optics to control the stray helium ions. Both approaches have significant limitations that must be overcome before irm techniques can be used in routine applications, in particular for measuring hydrogen isotopes from GC effluents (irm-GCMS). PMID- 22088119 TI - Isotope-Ratio-Monitoring Liquid Chromatography Mass Spectrometry (IRM-LCMS): First Results from a Moving Wire Interface System. AB - Abstract A Liquid Chromatography-Combustion (LC-C) Interface, based on a moving wire technique, has been built and tested. The LC effluent is deposited onto a transport wire, which carries the sample through solvent evaporation and combustion ovens. CO(2) from the combustion step is analysed in an isotope ratio mass spectrometer. Performance of the interface was tested by loop injections of sucrose and glucose into a liquid flow of methanol/water (80/20). Accuracy and precision of delta(13)C(PDB) < 10/00 was achieved for sample concentrations > 500 ng/ul (5MUl loop), sufficient for studies at natural isotope ratios. In case of (13)C tracer applications the detection limit was determined to be about 20 pg carbon tracer (on wire). PMID- 22088120 TI - Forensic Studies by EA-IRMS. AB - Abstract The authenticity of natural and synthetic matter can be checked by measurement of the isotope ratios of C, N and S. Controlled substances like drugs of abuse (cocaine, heroin) and explosives (TNT) or, simply, traces of paint can hold information in their isotope pattern. Total combustion of samples in an elemental analyzer followed by on-line determination of the isotopes of the combustion products (CO(2), N(2), SO(2)) in an isotope ratio mass spectrometer (EA-IRMS) provides high sample throughout with a minimum of sample preparation. PMID- 22088121 TI - Accuracy and precision for measurements of the mass ratio 30/28 in dinitrogen from air samples and its application to the investigation of N losses from soil by denitrification. AB - Abstract In the 1950s Hauck introduced a special version of the (15)N dilution technique ((15)N flux method) for the determination of N losses from the soil by denitrification. Although this method is very useful and reliable its application has been rather infrequent up to now. This is mainly due to the need to measure the m/z 30 in addition to the usually measured m/z 28 and 29 for dinitrogen, because the (15)N in the enriched air sample taken from an enclosure (cover box) at the soil surface is nonrandom. The signal from the m/z 30 is very low and difficult to measure with sufficient precision because other species (e.g. NO) also having the m/z 30 often interfere with its measurement. In this study the accuracy and precision of an easy to use CF-IRMS with sample batch operation to measure the ratio 30/28 was investigated. The relative standard deviation (RSD = precision) from natural abundance up to 2 at.% was always <1%. After correction of the mass ratio 30/28 (R30), by means of a formula obtained by linear regression of theoretical R30 against measured R30, the accuracy of the abundance calculated from this corrected R30 was very high. From the achieved precision and assuming a cover box height of 10 cm (headspace volume of 7 1), and a collection time of 2 h, a limit of detection for N(2) losses by denitrification equivalent to 16 g N/ha*d or 6 kg N/ha*a can be estimated. The performance of the (15)N dilution method using the equipment and procedure described is demonstrated by means of results from an incubation experiment with [(15)N]nitrate-amended soils. PMID- 22088122 TI - (18)O/(16)O and (13)c/(12)c fractionation during the reaction of carbonates with phosphoric Acid: effects of cationic substitution and reaction temperature. AB - Abstract The factors for (18)O/(16)O fractionation between carbonates and CO(2) gas produced by the dissolution of the carbonates in phosphoric acid (sealed vessel method) have been investigated as a function of reaction temperature (20 90 degrees C) and cationic substitution in the solid. Synthetic CaCO(3), Ca(0.75) Mn(0.25) CO(3), MnCO(3), BaCO(3) and SrCO(3) powders, and a natural kutnahorite sample were used as solids. The delta(18)O values of the gaseous CO(2) liberated by the reaction with phosphoric acid decrease with increasing temperature and seem to be a linear function of T( degrees K)(-2). The slopes are specific for different carbonates. No temperature-depended (13)C/(12)C fractionation seems to exist. PMID- 22088124 TI - Editorial board page for "Isotopes in Environmental and Health Studies", Volume 32, Number 2-3. AB - Abstract This is a scanned image of the original Editorial Board page(s) for this issue. PMID- 22088125 TI - Genetic diversity of thiamin and folate in primitive cultivated and wild potato (Solanum) species. AB - Biofortification of staple crops like potato via breeding is an attractive strategy to reduce human micronutrient deficiencies. A prerequisite is metabolic phenotyping of genetically diverse material which can potentially be used as parents in breeding programs. Thus, the natural genetic diversity of thiamin and folate contents was investigated in indigenous cultivated potatoes (Solanum tuberosum group Andigenum) and wild potato species (Solanum section Petota). Significant differences were found among clones and species. For about 50% of the clones there were variations in thiamin and folate contents between years. Genotypes which contained over 2-fold the thiamin and 4-fold the folate content compared to the modern variety Russet Burbank were identified and should be useful material to integrate in breeding programs which aim to enhance the nutritional value of potato. Primitive cultivars and wild species with widely different amounts of thiamin and folate will also be valuable tools to explore their respective metabolic regulation. PMID- 22088127 TI - Banking sperm is only the first of many decisions for men: what healthcare professionals and men need to know. AB - Sperm banking is recommended for all males prior to cancer treatment where there are risks of infertility. Subsequent decisions about monitoring fertility, use of banked sperm or disposal are less well understood, with adverse consequences for men and cost implications. We review the literature around key decision points: Diagnosis of cancer, monitoring fertility, use of banked sperm and sperm disposal. The results suggest that decisions about banking are compromised by concerns to initiate treatment quickly; subsequent decisions about monitoring fertility, use of banked sperm or disposal are coloured by the views of family members, men's failure to understand the longer-term implications and their reluctance to avail themselves of health care generally. Methodological limitations of current research include low response rates, increased focus on germ cell cancers and a lack of research outside North America. There is evidence that men and oncologists could use sperm banks more "wisely". Lack of longitudinal work means it is not possible to determine the long-term consequences of banking for men's general health and well-being, or identify barriers to fertility monitoring or disposal. We argue that sperm banking should be considered as a series of decisions, all involving implications for fertility, contraception and social and psychological adjustment to cancer. PMID- 22088128 TI - Psychosocial trends in couples prior to commencement of in vitro fertilisation (IVF) treatment. AB - Facing infertility and undergoing fertility treatment can create emotional turmoil in couples' lives. It is essential for fertility therapy providers to assess the coping and communication strategies of couples before treatment in order to provide appropriate support. We performed a two time point (year 2003 & year 2009) cross-sectional study of patients attending our services to undergo in vitro fertilisation. All couples attending the Human Assisted Reproduction Ireland Unit, a tertiary referral academic centre at the Rotunda Hospital, were requested to complete a psychosocial questionnaire before commencing the treatment. The questions assessed couples' understanding of their own infertility, family background and support, relationship traits and stress levels prior to commencing fertility treatment. A total of 180 patients participated in the study. Our findings showed that within a 6-year time span, couples' attitudes have changed significantly. Compared to 6 years ago, couples now have a better understanding of infertility and are seeking treatment quicker. Interestingly, we showed higher stress levels nowadays with fewer couples following routine stress management. We also identified specific gender differences in that women have a more open attitude in discussing infertility and seeking more support from friends and family compared to men. PMID- 22088129 TI - Viral screening before each cycle of assisted conception treatment is expensive and unnecessary: a survey of results from a UK inner city clinic. AB - The European Union Tissues and Cells Directive requires screening of tissue and cell donors for infective organisms to prevent inter-patient transmission. The Directive includes the unique term partner donation, which refers to "donation of reproductive cells between a man and a woman who declare that they have an intimate physical relationship". In line with the Directive, partners undergoing Assisted Reproductive Technology (ART) now require screening before each treatment, regardless of the time interval between consecutive cycles. Evidence to support this recommendation is lacking. Therefore, we conducted a retrospective study of all virology screening tests undertaken over a three year period for individuals attending an assisted conception unit serving a high risk inner city population. We ascertained prevalence and seroconversion rates for HIV, hepatitis B and C and estimated the additional cost of implementing the Directive fully in our unit. With more than 3910 ART individuals screened between January 2007 and December 2009, the prevalence of HIV, hepatitis B and C was 0.6, 1.7 and 0.4%, respectively. A total of 422 individuals had a second screening test during the three year period and none seroconverted. This study suggests that increasing the frequency of screening individuals undergoing ART to less than 12 months would not confer added benefit and has significant cost implications. PMID- 22088131 TI - Full investigation of patients with polycystic ovary syndrome (PCOS) presenting to four different clinical specialties reveals significant differences and undiagnosed morbidity. AB - OBJECTIVE: This study aimed to compare the spectrum of polycystic ovary syndrome (PCOS) symptoms in patients from four different specialist clinics. DESIGN: A prospective cross-sectional observational study. SETTING: The study was conducted at the infertility, gynaecology, endocrine and dermatology clinics at Leeds General Infirmary, U.K. PATIENTS: Seventy women presenting with features of PCOS: 20 from infertility, 17 from gynaecology, 17 from dermatology and 16 from endocrine clinics. INTERVENTIONS: Participants were assessed for symptoms and signs of PCOS and underwent a full endocrine and metabolic profile and a pelvic ultrasound scan. RESULTS: All subjects had experienced menstrual problems, 81% were overweight, 86% had polycystic ovaries on ultrasound, 56% had hirsutism, 53% had acne, 23% had acanthosis nigricans, 16% had alopecia and 38% had previously undiagnosed impaired glucose tolerance (IGT) or diabetes. A significant difference between the four clinic groups existed with regard to menstrual patterns (p = 0.0234), frequency distribution of presenting symptoms and the percentages of patients with PCOS who had already been diagnosed as having PCOS (p = 0.0088). CONCLUSION: This study emphasizes the importance of understanding the full spectrum of PCOS as presented to different specialty clinics. Not only is the syndrome under diagnosed but also are the significant associated morbidities such as IGT and type 2 diabetes. Different specialists need to appreciate the spectrum of health problems for women with PCOS that may extend beyond the specific symptoms that precipitated the initial referral. PMID- 22088130 TI - Anti-Mullerian Hormone (AMH) levels in serum and follicular fluid as predictors of ovarian response in stimulated (IVF and ICSI) cycles. AB - INTRODUCTION: Anti-Mullerian Hormone (AMH) was recently introduced as a marker of ovarian reserve in assisted reproduction. The cutoff values of AMH for prediction of poor response have not yet been determined. MATERIAL AND METHODS: Ninety women undergoing their first IVF/ICSI cycle were prospectively included in this clinical, non-interventional study. Baseline AMH, follicle stimulating hormone (FSH) and antral follicle count (AFC) were measured before starting ovarian stimulation. AMH was also measured on day 5 of stimulation and in the follicular fluid of the first aspirated follicle. The predictive value of baseline AMH, day 5 AMH and follicular fluid AMH were assessed comparatively to FSH and AFC for ovarian response. Ovarian response was defined as poor (<4 oocytes), high (>12 oocytes) or normal (>=4 oocytes and <=12 oocytes). However, only 3 patients met the criterion for high ovarian response and thus analysis was focused on the prediction of poor response. RESULTS: Significant differences were present between poor responders and non-poor responders regarding FSH (p = 0.019), baseline AMH (p = 0.002), AFC (p < 0.001), day 5 AMH (p = 0.005) but not for follicular AMH (p = 0.183). The largest AUC (area under the curve) for poor ovarian response was obtained by AFC (AUC = 0.81) followed by baseline AMH (AUC = 0.70). At a level below 2.74 ng/mL, the sensitivity of the test is 69% and specificity is 70.5%. CONCLUSION: Baseline AMH is almost as good a predictor for poor ovarian response as AFC. PMID- 22088132 TI - Inverse opals of molecularly imprinted hydrogels for the detection of bisphenol A and pH sensing. AB - Inverse opal films of molecularly imprinted polymers (MIP) were elaborated using the colloidal crystal template method. The colloidal crystals of silica particles were built by the Langmuir-Blodgett technique, allowing a perfect control of the film thickness. Polymerization in the interspaces of the colloidal crystal in the presence of bisphenol A (BPA) and removal of the used template provides 3D ordered macroporous methacrylic acid-based hydrogel films in which nanocavities derived from bisphenol A are distributed within the thin walls of the inverse opal hydrogel. The equilibrium swelling properties of the nonimprinted (NIPs) and molecularly imprinted polymers (MIPs) were studied as a function of pH and bisphenol A concentration, while the molecular structures of the bulk hydrogels were analyzed using a cross-linked network structure theory. This study showed an increase in nanopore (mesh) size in the MIPs after BPA extraction as compared to NIPs, in agreement with the presence of nanocavities left by the molecular imprints of the template molecule. The resulting inverse opals were found to display large responses to external stimuli (pH or BPA) with Bragg diffraction peak shifts depending upon the hydrogel film thickness. The film thickness was therefore shown to be a critical parameter for improving the sensing capacities of inverse opal hydrogel films deposited on a substrate. PMID- 22088133 TI - Assessing the efficacy of the Healthy Eating and Lifestyle Programme (HELP) compared with enhanced standard care of the obese adolescent in the community: study protocol for a randomized controlled trial. AB - BACKGROUND: The childhood obesity epidemic is one of the foremost UK health priorities. Childhood obesity tracks into adult life and places individuals at considerable risk for diabetes, cardiovascular disease, liver disease and other morbidities. There is widespread need for paediatric lifestyle programmes as change may be easier to accomplish in childhood than later in life. STUDY DESIGN/METHOD: The study will evaluate the management of adolescent obesity by conducting a Medical Research Council complex intervention phase III efficacy randomised clinical trial of the Healthy Eating Lifestyle Programme within primary care. The study tests a community delivered multi-component intervention designed for adolescents developed from best practice as identified by National Institute for Health and Clinical Excellence. The hospital based pilot reduced body mass index and improved health-related quality of life.Subjects will be individually randomised to receiving either the Healthy Eating Lifestyle Programme (12 fortnightly family sessions) or enhanced standard care. Baseline and follow up assessments will be undertaken blind to allocation status. A health economic evaluation is also being conducted.200 obese young people (13-17 years, body mass index > 98th centile for age and sex) will be recruited from primary care within the greater London area.The primary hypothesis is that a motivational and solution-focused family-based weight management programme delivered over 6 months is more efficacious in reducing body mass index in obese adolescents identified in the community than enhanced standard care.The primary outcome will be body mass index at the end of the intervention, adjusted for baseline body mass index, age and sex.The secondary hypothesis is that the Healthy Eating Lifestyle Programme is more efficacious in improving quality of life and psychological function and reducing waist circumference and cardiovascular risk factors in obese adolescents than enhanced standard care assessed at 6 and 12 months post baseline assessment.Improvement in quality of life predicts on-going lifestyle change and maximises the chances of long-term weight reduction. We will explore whether improvement in QOL may be intermediate on the pathway between the intervention and body mass index change. TRIAL REGISTRATION: ISRCTN: ISRCTN99840111. PMID- 22088134 TI - The effect of local environmental variables on the helminth parasite communities of the pointedbelly frog Leptodactylus podicipinus from ponds in the Pantanal wetlands. AB - Understanding the patterns of species distribution and abundance has been at the core of ecology. In general, these patterns are determined by species dispersion as well as by abiotic and biotic environmental conditions. Similarly, host parasite relations and the structure of parasite assemblages are also shaped by environmental conditions and landscape composition. Herein, we assessed the influence of environmental variables and parasite species dispersion on the structure of helminth parasites communities in the frog Leptodactylus podicipinus. We sampled 10 ponds and recorded area, depth, altitude, pH, dissolved oxygen, salinity, temperature, and extent of soil, water, and vegetation cover as well as the distances between the ponds. We collected 121 frogs and found 9 helminth taxa; 2 of them were core species (prevalence higher than 50%), which contributed to the relatively high similarity observed among the ponds. Most of the helminths showed some variation in the frequencies of occurrence among communities from different ponds. The change in species composition among ponds was explained by the environmental variables but not by the distance between the ponds. Moreover, the results indicated that local processes (variation in environmental conditions) were more important than the regional processes (species distribution) in determining the structure of parasite communities. The variation in helminth communities among ponds in response to moderate differences in pond environmental characteristics points to the potential of helminth species as indicators of environmental conditions. PMID- 22088135 TI - Retraction. Polyethyleneimine-based gene therapy by inhalation. PMID- 22088136 TI - Orientation-dependent electron transport in a single redox protein. AB - The redox-active protein cytochrome b(562) has been engineered to introduce pairs of thiol groups in the form of cysteine residues at specified sites. Successful STM imaging of the molecules adsorbed on a gold surface indicated that one thiol group controls the orientation of the molecule and that the protein maintains its native form under the experimental conditions. Stable protein-gold STM tip electrical contact was directly observed to form via the second free thiol group in current-voltage and current-distance measurements. Proteins with thiol contacts positioned across the protein's short axis displayed a conductance of (3.48 +/- 0.05) * 10(-5)G(0). However proteins with thiol groups placed along the long axis reproducibly yielded two distinct values of (1.95 +/- 0.03) * 10( 5)G(0) and (3.57 +/- 0.11) * 10(-5)G(0), suggesting that the placement of the asymmetrically located haem within the protein influences electron transfer. In contrast, the unengineered wild-type cytochrome b(562) had conductance values at least 1 order of magnitude less. Here we show that an electron transfer protein engineered to bind gold surfaces can be controllably oriented and electrically contacted to metallic electrodes, a prerequisite for potential integration into electronic circuits. PMID- 22088137 TI - Dietary intake of artificial sweeteners by the Belgian population. AB - This study investigated whether the Belgian population older than 15 years is at risk of exceeding ADI levels for acesulfame-K, saccharin, cyclamate, aspartame and sucralose through an assessment of usual dietary intake of artificial sweeteners and specific consumption of table-top sweeteners. A conservative Tier 2 approach, for which an extensive label survey was performed, showed that mean usual intake was significantly lower than the respective ADIs for all sweeteners. Even consumers with high intakes were not exposed to excessive levels, as relative intakes at the 95th percentile (p95) were 31% for acesulfame-K, 13% for aspartame, 30% for cyclamate, 17% for saccharin, and 16% for sucralose of the respective ADIs. Assessment of intake using a Tier 3 approach was preceded by optimisation and validation of an analytical method based on liquid chromatography with mass spectrometric detection. Concentrations of sweeteners in various food matrices and table-top sweeteners were determined and mean positive concentration values were included in the Tier 3 approach, leading to relative intakes at p95 of 17% for acesulfame-K, 5% for aspartame, 25% for cyclamate, 11% for saccharin, and 7% for sucralose of the corresponding ADIs. The contribution of table-top sweeteners to the total usual intake (<1% of ADI) was negligible. A comparison of observed intake for the total population with intake for diabetics (acesulfame-K: 3.55 versus 3.75; aspartame: 6.77 versus 6.53; cyclamate: 1.97 versus 2.06; saccharine: 1.14 versus 0.97; sucralose: 3.08 versus 3.03, expressed as mg kg(-1) bodyweight day(-1) at p95) showed that the latter group was not exposed to higher levels. It was concluded that the Belgian population is not at risk of exceeding the established ADIs for sweeteners. PMID- 22088138 TI - DOF-binding sites additively contribute to guard cell-specificity of AtMYB60 promoter. AB - BACKGROUND: We previously demonstrated that the Arabidopsis thaliana AtMYB60 protein is an R2R3MYB transcription factor required for stomatal opening. AtMYB60 is specifically expressed in guard cells and down-regulated at the transcriptional levels by the phytohormone ABA. RESULTS: To investigate the molecular mechanisms governing AtMYB60 expression, its promoter was dissected through deletion and mutagenesis analyses. By studying different versions of AtMYB60 promoter::GUS reporter fusions in transgenic plants we were able to demonstrate a modular organization for the AtMYB60 promoter. Particularly we defined: a minimal promoter sufficient to confer guard cell-specific activity to the reporter gene; the distinct roles of different DOF-binding sites organised in a cluster in the minimal promoter in determining guard cell-specific expression; the promoter regions responsible for the enhancement of activity in guard cells; a promoter region responsible for the negative transcriptional regulation by ABA. Moreover from the analysis of single and multiple mutants we could rule out the involvement of a group of DOF proteins, known as CDFs, already characterised for their involvement in flowering time, in the regulation of AtMYB60 expression. CONCLUSIONS: These findings shed light on the regulation of gene expression in guard cells and provide new promoter modules as useful tools for manipulating gene expression in guard cells, both for physiological studies and future biotechnological applications. PMID- 22088139 TI - Chemical interactions between an active pharmaceutical ingredient and its counterion in a tromethamine salt under forced degradation conditions. AB - In this study, the tromethamine salt of an active pharmaceutical ingredient containing both a carboxylic acid and ethyl ester functionality was subjected to forced degradation conditions. Based on HPLC-MS analysis, it was found that tromethamine formed both amide and ester type condensation products with the API, with amide formation predominating over ester formation. Addition of tromethamine at the carboxylic acid group of the API was favored over addition at the ethyl ester group. Tromethamine condensation products were observed only under the harshest stress conditions (80 degrees and 75% relative humidity), in which the salt physically changed from a crystalline form to a deliquesced state. Under stress conditions in which the crystalline structure of the salt remained intact, good stability was observed. Thus, the interaction between tromethamine and API occurred only in cases where the crystallinity of the salt was compromised. PMID- 22088140 TI - Clinicopathological, therapeutic and prognostic features of the triple-negative tumors in moroccan breast cancer patients (experience of Hassan II university hospital in Fez). AB - INTRODUCTION: Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors (ER, PR) and Her2, we can distinguish between two groups: basal-like (ER-, PR-, Her2-, cytokeratin (CK) 5/6+ and/or Her1+) and unclassified subtype (ER-, PR-, Her2-, Her1- and CK5/6-).The aim of this study is to determine the clinicopathological, histological, therapeutic and prognostic features associated with this type of breast cancer. METHODS: This is a retrospective study of 366 female breast cancer patients, diagnosed between January 2007 and June 2010 at the Department of Pathology. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome. RESULTS: A total of 64 women were identified as having TNBC (17.5% of all female breast cancer patients), 12.6% were basal like, 4.9% were unclassified subtype, with a median age of 45 years. The median histological tumor diameter was 4.3 cm. TNBC were most often associated with a high grade, 49.2% grade III (53% for unclassified subtype, 47.6% for basal-like). Vascular invasion was found in 26.6% of cases (22% for unclassified subtype and 28.3% for basal-like). For the lymph node involvement: 51% had positive lymph nodes, and 22.4% had distant metastases. Neoadjuvant chemotherapy was administered to 18% patients with 26% of complete pathologic response; therefore adjuvant chemotherapy was given to 82%. 98% received anthracycline based regimen and only 30% received taxanes.The Kaplan-Meier curves based showed the lowest survival probability at 3-years (49% of OS, and 39% of DFS). CONCLUSION: TNBC is associated with young age, high grade tumors, advanced stage at diagnosis, difference chemo response compared to other subtypes, and shortest survival. Critical to optimal future management is accurate identification of truly triple negative disease, and adequately powered prospective TNBC trials to establish treatment efficacy and define predictive biomarkers. PMID- 22088141 TI - An approach to the stereoselective synthesis of enantiopure dihydropyrroles and aziridines from a common sulfinyl-sulfinamide intermediate. AB - The diastereoselective addition of lithiated vinyl sulfoxides to enantiopure sulfinimines provides direct access to a wide assortment of allylic sulfinamides in good yields and excellent selectivities. These adducts are key precursors to differently functionalized cis- and trans-dihydropyrroles. Modulation of the protecting group on nitrogen prior to cyclization has a significant impact on the stereochemical outcome, allowing for the selective preparation of 2,5-cis- or 2,5 trans-3-sulfinyl disubstituted dihydropyrroles from a common sulfinamide intermediate. Further research on halocyclization conditions has also yielded a stereoselective synthesis of trisubstituted vinyl aziridines from these chiral sulfinamides, simply by changing the halogenating agent. PMID- 22088142 TI - Involvement of the epidermal growth factor receptor in the modulation of multidrug resistance in human hepatocellular carcinoma cells in vitro. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a molecular complex tumor with high intrinsic drug resistance. Recent evidence suggests an involvement of the tyrosine kinase pathway in the regulation of ATP-binding cassette protein (ABC transport protein) mediated multidrug resistance in cancer cells. The aim of this study was to examine whether EGFR inhibition sensitizes HCCs to chemotherapy and to elucidate its mechanism. RESULTS: Chemotherapeutic treatment induces multidrug resistance and significantly increases ABC-transport protein expression and function in a time- and dose-dependent manner in HCC cells. Furthermore, cytostatic treatment increases the mRNA expression of tyrosine kinases and induces the phosphorylation of ERK. EGF activation of the tyrosine kinase pathway up-regulated the ABC-transport protein mRNA expression and enhanced the survival of resistant HCC cells. Consistent with these effects, inhibition of the EGFR using siRNA decreased the ABC-transport protein mRNA expression and inhibited the proliferation of resistant cells. Additional treatment with Gefitinib, a clinically approved EGFR inhibitor, caused a dose-dependent reversal of resistance to conventional chemotherapy. CONCLUSION: The present study demonstrates that the multidrug resistance of HCC is modulated through the EGF activated tyrosine kinase cascade. Consequentially, the restoration of chemosensitivity by EGFR inhibition may lead towards new tailored therapies in patients with highly resistant tumors. PMID- 22088144 TI - Interface effects on the magnetism of CoPt-supported nanostructures. AB - The magnetism of CoPt nanostructures supported on the MgO(100) surface is investigated via first-principles simulations using 1D models. Nanostructures with L1(0) chemical ordering and cube-on-cube epitaxy are predicted to possess large magnetic moments and easy magnetization axis perpendicular to the surface. However, their magnetic anisotropy energy is roughly halved with respect to the bulk alloy due to a peculiar mixing of particle and support electronic states. The general factors at play in determining this behavior and the implications of these findings are discussed in view of designing room-temperature magnetic bits. PMID- 22088143 TI - Dependence of avidity on linker length for a bivalent ligand-bivalent receptor model system. AB - This paper describes a synthetic dimer of carbonic anhydrase, and a series of bivalent sulfonamide ligands with different lengths (25 to 69 A between the ends of the fully extended ligands), as a model system to use in examining the binding of bivalent antibodies to antigens. Assays based on analytical ultracentrifugation and fluorescence binding indicate that this system forms cyclic, noncovalent complexes with a stoichiometry of one bivalent ligand to one dimer. This dimer binds the series of bivalent ligands with low picomolar avidities (K(d)(avidity) = 3-40 pM). A structurally analogous monovalent ligand binds to one active site of the dimer with K(d)(mono) = 16 nM. The bivalent association is thus significantly stronger (K(d)(mono)/K(d)(avidity) ranging from ~500 to 5000 unitless) than the monovalent association. We infer from these results, and by comparison of these results to previous studies, that bivalency in antibodies can lead to associations much tighter than monovalent associations (although the observed bivalent association is much weaker than predicted from the simplest level of theory: predicted K(d)(avidity) of ~0.002 pM and K(d)(mono)/K(d)(avidity) ~ 8 * 10(6) unitless). PMID- 22088145 TI - Changes in condom use during a microbicide clinical trial in Pune, India. AB - Researchers have raised concerns that microbicide use during clinical trials would displace condom use. We sought to understand whether condom use changed for participants in a microbicide clinical trial in Pune, India, to understand whether condom shifts were a legitimate concern. We hypothesize that women participating in a microbicide clinical trial in Pune, India, were more likely, on average, to report condom use at follow-up. We further hypothesize that men, whose female partners participated in a microbicide clinical trial were more likely, on average, to report condom use at follow-up. The outcome measure for reported condom use was a dichotomous variable to indicate whether or not the participant had used a male or female condom with a sexual partner since 2 months before enrollment or since the last survey, depending on the visit. Data are from semi-structured interviews at baseline, 2 months, 4 months, and 6 months with HPTN 059 clinical trial participants (100 women and 57 male partners). We used generalized estimating equations with a logit link function, exchangeable correlation, and a binomial family to model condom use. The odds of condom use for clinical trial women increased from baseline to 6 months by a factor of 3.7 (95% CI: 1.84-7.63) and the change in odds of condom use for clinical trial men from baseline to 6 months increased by a factor of 2.58 (95% CI: 1.37-4.85). We found concerns about microbicide use displacing condom use were not merited in this study population. The percent of participants reporting condom use declined from 4 to 6 months, suggesting that increases in condom use may only be during active study participation. Information about clinical trial factors that enabled these men and women to enact this important HIV prevention behavior is needed to develop interventions. PMID- 22088146 TI - Detection of enzymatically generated hydrogen peroxide by metal-based fluorescent probe. AB - We developed a metal-based fluorescent probe for H(2)O(2) called MBFh1, which has an iron complex as a reaction site for H(2)O(2) and a 3,7-dihydroxyphenoxazine derivative as the fluorescent reporter unit. The iron complex reacts quickly with H(2)O(2) to form oxidants, and then the oxidants convert the closely appended nonfluorescent 3,7-dihydroxyphenoxazine moiety to resorufin in an intramolecular fashion. The quick response to H(2)O(2) allows us to plot the enzymatic evolution of H(2)O(2). A combination of N-acetyl-3,7-dihydroxyphenoxazine and horseradish peroxidase has been frequently used to detect enzymatically generated H(2)O(2), but this method has interference with phenol derivatives. The use of MBFh1 overcomes this drawback. PMID- 22088147 TI - Prevalence and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus among pigs in Belgium. AB - The prevalence, distribution, and antimicrobial susceptibility of methicillin resistant Staphylococcus aureus (MRSA) in Belgian pig farms has been investigated. To that end, nasal samples were collected from 1,500 pigs on 50 farms randomly selected over Belgium. Both closed (breeding or farrow-to-finish) and open (fattening) farms were included. Within closed farms different age groups were investigated. A total number of 663 (44%) pigs belonging to 34 (68%) farms carried MRSA. According to their management practice, MRSA was detected on 94% of the open farms and 56% of the closed farms. Focusing on the in-herd prevalence among fattening pigs for both management systems, a significantly higher rate was found in open farms (72%) compared to closed farms (26%). Within the closed farms, piglets (41%) showed a higher MRSA prevalence than sows (26%) and fattening pigs (26%). All strains tested were ST398 and showed mainly spa type t011, as commonly found on pig herds in Europe. Less dominating spa-types were t034, t567, and t2970. The MRSA strains carried two SCCmec-types, type IVa or V. All 643 MRSA strains were resistant to tetracycline and additional resistances to trimethoprim (97%), lincosamides (73%), macrolides (56%), aminoglycosides (48%), and fluoroquinolones (32%) were found. Multiresistance (defined as resistance to four or more non-beta-lactam antimicrobial classes) was found in 63% of the tested strains. In conclusion, a high prevalence of MRSA was found in Belgian pig farms, with the highest prevalence in open farms. In accordance with other European countries, age-related and management-related differences in MRSA prevalence were observed that should be considered when control strategies are outlined. PMID- 22088148 TI - Chemical trapping of vancomycin: a potential strategy for preventing selection of vancomycin-resistant Enterococci. AB - Emergence of antimicrobial resistance is among the most worrisome issues in public health worldwide. Vancomycin resistance is rapidly spreading, resulting in increased morbidity, mortality, and healthcare-associated costs. Multiple strategies are required to preserve the effectiveness of this essential antibiotic. It has been recently shown that biliary excretion of vancomycin following parenteral administration results in significant fecal concentrations of vancomycin that may lead to selection of vancomycin-resistant strains within the colon. In this study we present a novel strategy for preventing this undesired effect and its consequences, using chemical trapping of vancomycin by a tripeptide analog that mimics the natural bacterial vancomycin binding-site. Initially, we demonstrated that a tripeptide analog can neutralize vancomycin activity against Enterococci at a molar excess of 28. In the second phase, two chemical modifications, designed to attach the tripeptide to vancomycin covalently, were explored. Attachment of a 4-flurosulfonyl-benzoic acid (FSBA) moiety to the parent tripeptide resulted in vancomycin neutralization at a molar ratio of less than 4:1. Finally it was shown that the FSBA-bound tripeptide analog can prevent in-vitro selection of vancomycin-resistant Enterococci (VRE) from a mixed vancomycin susceptible/resistant population following exposure to vancomycin. These findings demonstrate the ability of the proposed strategy to prevent selection of VRE. The present proof-of-concept study provides the basis for further development of the proposed strategy. Further, this strategy may be implemented for combating resistance to other antimicrobials. PMID- 22088150 TI - An exploration of person-centredness in practice. AB - Person-centredness' is a term that is becoming increasingly familiar within health and social care at a global level; it is being used to describe a standard of care that ensures the patient/client is at the centre of care delivery. In this article we explore the relevance of person-centredness in the context of nursing, taking account of the ongoing critical debate and dialogue regarding developments in this field. Person-centredness is recognised as a multidimensional concept. The complexity of the concept contributes to the challenge of articulating its shared meaning and describing how it can be applied in practice. The aim of this paper is to explore some of the issues pertaining to language and conceptual clarity, with a view to making connections and increasing our shared understanding of person-centred care in a way that can impact nursing practice. We begin by describing the development of the concept of person centredness, after which we discuss the synergies with patient-centredness and other related terms, and consider how nurses can operationalise person centredness in their practice. PMID- 22088149 TI - Effects of multi-walled carbon nanotubes (MWCNT) under Neisseria meningitidis transformation process. AB - BACKGROUND: This study aimed at verifying the action of multi-walled carbon nanotubes (MWCNT) under the naturally transformable Neisseria meningitidis against two different DNA obtained from isogenic mutants of this microorganism, an important pathogen implicated in the genetic horizontal transfer of DNA, causing the escape of the principal vaccination measured worldwide by the capsular switching process. MATERIALS AND METHODS: The bacterium receptor strain C2135 was cultivated and had its mutant DNA donor M2 and M6, which received a receptor strain and MWCNT at three different concentrations. The inhibition effect of DNAse on the DNA in contact with nanoparticles was evaluated. RESULTS: The results indicated an in increase in the transformation capacity of N. meninigtidis in different concentrations of MWCNT when compared with negative control without nanotubes. A final analysis of the interaction between DNA and MWCNT was carried out using Raman Spectroscopy. CONCLUSION: These increases in the transformation capacity mediated by MWCNT, in meningococci, indicate the interaction of these particles with the virulence acquisition of these bacteria, as well as with the increase in the vaccination escape process. PMID- 22088151 TI - Patients first! Engaging the hearts and minds of nurses with a patient-centered practice model. AB - Like every healthcare system today, the Cleveland Clinic health system is a combination of medical hospitals, institutes, and services in which the implementation of uniform care methodologies faces significant barriers. The guiding principle of the Cleveland Clinic, 'Patients First,' focuses on the principle of patient- and family-centered care (PFCC) but deliberately lacks details due to the wide scope of care delivered by the organization. The Stanley Shalom Zielony Institute of Nursing Excellence (the Nursing Institute) at the Cleveland Clinic was charged with standardizing nursing practice across a system with 11,000 registered nurses and 800 advanced practice nurses. The challenge involved providing firm direction on delivering PFCC that was appropriate for all clinical disciplines and could be implemented quickly across existing practices and technologies. Successful implementation required full engagement in the concept of PFCC by what the Institute for Healthcare Improvement has termed the 'hearts and minds' of nurses. To achieve these ends, development of a systemwide nursing practice model was initiated. In this article the authors identify the essence of PFCC, consider barriers to PFCC, review their process of developing PFCC, and describe how the Cleveland Clinic health system has implemented a PFCC nursing practice model. In doing so the authors explore how the concept of 'Passion for Nursing' was used to stimulate nurse engagement in PFCC. PMID- 22088152 TI - Developing person-centred care: addressing contextual challenges through practice development. AB - Developing person-centred care is not a one-time event; rather it requires a sustained commitment from organisations to the ongoing facilitation of developments, a commitment both in clinical teams and across organizations. Contextual factors pose the greatest challenge to person-centredness and the development of cultures that can sustain person-centred care. We will begin with a general comment on 'context' and its meaning before exploring three particular factors that influence the practice context, namely, workplace culture, learning culture, and the physical environment. Next we explore a particular approach to developing person-centred care through emancipatory practice development. We highlight the importance of facilitation through emancipatory practice development programmes and describe how person-centred care can be developed through the presentation of a case study that illustrates the principles and processes of emancipatory practice development as well as the outcomes achieved. We conclude with an application to clinical practice. A key consideration for all organisations in the development of person-centred care is to move from what we suggest are 'person-centred moments' (individual, ad hoc experiences of person centredness) to 'person-centred care' as an underpinning culture of teams and organisations. PMID- 22088153 TI - Patient-centered care in a medical home. AB - There is general consensus that our current healthcare delivery system will not be able to supply an adequate workforce, contain costs, and meet the ever increasing chronic-care needs of the growing and aging population in the United States (US). Some of the major challenges to the U.S. healthcare system are faced by those on the front lines, namely the healthcare workers in primary care. Part of the emerging solution for primary care is the adoption of the Patient-Centered Medical Home Model. The intent of this model is to provide coordinated and comprehensive care rooted in a strong collaborative relationship. Carilion Clinic in Southwestern Virginia is implementing this patient-centered model in which a proactive, multidisciplinary care team collectively takes responsibility for each patient. In this article we will elaborate on the concepts of patient-centered care and patient-centered medical homes, after which we will offer an exemplar describing the process that Carilion Clinic is using to establish patient centered medical homes throughout their primary care departments. Limitations of the Patient-Centered Medical Home Model will also be discussed. PMID- 22088154 TI - Delivering patient-centered care in the midst of a cultural conflict: the role of cultural competence. AB - At the core of both patient centeredness and cultural competence is the importance of seeing the patient as a unique person. For the purpose of this article, cultural competence is viewed as an expansion of patient-centered care. More specifically, cultural competence can be seen as a necessary set of skills for nurses to attain in order to render effective patient-centered care. However, a vexing question remains, "How does the nurse deliver patient-centered care when the patient's health beliefs, practices, and values are in direct conflict with medical and nursing guidelines?" The purpose of this article is to provide nurses with a set of culturally competent skills that will enhance the delivery of patient-centered care in the midst of a cultural conflict. I will begin by offering a conceptual framework for cultural competence and a description of the cultural skill needed to formulate a mutually acceptable and culturally relevant treatment plan for each patient. Next I will describe effective approaches for cultural encounters. Finally I will present a vignette that illustrates how the nurse can deliver patient-centered care when the patient's health beliefs, practices, and values are in direct conflict with medical and nursing guidelines. PMID- 22088155 TI - Teaching patient-centered care during the Silver Hour. AB - Teaching students and clinicians about end-of-life care is an important part of healthcare. Utilizing the framework of the Silver Hour is one method of illustrating the urgent, intense comfort needs required by patients and families throughout the imminently dying process, wherever the patient may be receiving services. When death is imminent, it is extremely important to provide patient- and family-centered care as the waning moments of life transition to the first moments of death. A variety of instructional methods can be used can be used to teach students to provide multidimensional, patient-centered care at the end of life. The author begins by describing the basic concept of patient-centered care and by discussing the importance of teaching students about this level of care. Next she describes the concept of the Silver Hour, along with a discussion of how the Silver Hour relates to nursing education. She also notes the importance of both role modeling in providing patient-centered care and of drawing upon the five ways of knowing to strengthen the teaching of students about care during the Silver Hour. PMID- 22088156 TI - The essence of nursing in the shifting reality of Israel today. AB - Israel's healthcare system is undergoing constant transformation; nurses' roles and education are changing accordingly. Israel's severe shortage of physicians has led to an increase in nurses' authority and responsibilities. The nursing profession is addressing many questions particularly in light of its expanded responsibilities and the current lack of legislation related to the practice of nursing. Additionally Israel is coping with an increasing shortage of nurses and the rapid development of innovative technologies. This article describes Israel's shifting reality and the nation's responses to these changing conditions. Responses include increasing financial support, enhancing educational opportunities, expanding the nursing role, and using new technologies. PMID- 22088157 TI - Moral distress and moral courage in everyday nursing practice. AB - In this article the author examines the concepts of moral distress and moral courage within the context of nursing practice. Examples of challenging healthcare situations from the United Kingdom and Ireland are discussed in the light of the examination of these two concepts. The examples illuminate features of healthcare situations that need to be considered in relation to different organisational and cultural contexts. This requires an understanding of the complexity of clinical contexts and an appreciation of the fallibility and vulnerability of nurses and other practitioners. The goal of this article is to encourage healthcare organisations to create supportive structures and sensitive leadership that will enhance moral courage in the work setting. PMID- 22088158 TI - Validation of the English and Spanish Mammography Beliefs and Attitudes Questionnaire. AB - Breast cancer is the leading cause of cancer deaths among Hispanic women in the United States. Unfortunately Hispanic women exhibit poor mammography screening participation, are diagnosed at later stages of the disease, and have lower survival rates than non-Hispanic white women. Several cultural and psycho-social factors have been found to influence mammography screening participation among Hispanic women. We will begin by presenting the theoretical framework that grounded this research program to develop an instrument to assess factors contributing to poor mammography participation among Hispanic women. We will also summarize the early stages in the development of the English and Spanish Mammography Beliefs and Attitudes Questionnaire (MBAQ and SMBAQ) for use with low health-literacy Mexican-American women. Next we will describe the initial psychometric testing of the MBAQ/SMBAQ, after which we will present the psychometric testing of the SMBAQ with low-health-literacy women. This will be followed by a discussion of the modification of the MBAQ and SMBAQ subscales. We'll conclude with a discussion of the instruments and share our assessment regarding the limitations of this research program, where the program stands to date, and the implications for practice and future research. PMID- 22088159 TI - Nursing at its best: competent and caring. AB - An award-winning journalist spoke to a group of students during their first month in a baccalaureate nursing program, challenging the nursing profession to abandon its image of nurses as angels and promote an image of nurses as competent professionals who are both knowledgeable and caring. This presentation elicited an unanticipated level of emotion, primarily anger, on the part of the students. This unexpected reaction prompted faculty to explore the students' motivations for entering the nursing profession and their perceptions of the relative importance of competence and caring in nursing. The authors begin this article by reviewing the literature related to motivations for selecting a profession and the contributions of competence and caring to nursing care. Next they describe their survey method and analysis and report their findings regarding student motivations and perceptions of competence and caring in nursing. Emerging themes for motivation reflected nursing values, especially altruism, and coincided with students' beliefs of self-efficacy and goal attainment. Student responses indicated their understanding of the need for competence and revealed idealistic perceptions of caring. The authors conclude with a discussion of these themes and recommendations for student recruitment, curricular emphasis, and future research in this area. PMID- 22088160 TI - Ethics: beyond patient care: practicing empathy in the workplace. PMID- 22088161 TI - Informatics: the standardized nursing terminologies: a national survey of nurses' experiences and attitudes. PMID- 22088162 TI - Genetic modification of low phytic acid 1-1 maize to enhance iron content and bioavailability. AB - High phytate content in staple food crops is a major barrier to successful iron biofortification. We have exploited the low phytic acid 1-1 (lpa1-1) mutant of maize to generate transgenic plants with up-to 70 MUg/g seed iron through the endosperm-specific overexpression of soybean ferritin, resulting in more than 2 fold improvement in iron bioavailability. The levels of bioavailable seed iron achieved in this study greatly exceed any achieved thus far and closely approach values estimated to have a nutritional impact on target populations. Gene expression studies reveal a large induction of the YS1 transporter in leaves and severe repression of an iron acquisition gene DMAS1 in roots, suggesting significant alterations in the iron homeostatic mechanisms in transgenic lpa1-1. Furthermore, preliminary tests show that the high-iron lpa1-1 seeds have higher germination rates and seedling vigor when compared to those of the nontransgenic seeds, which may help improve their value to plant breeders. PMID- 22088163 TI - Work-related stress and bullying: gender differences and forensic medicine issues in the diagnostic procedure. AB - BACKGROUND: The attention of international agencies and scientific community on bullying and work-related stress is increasing. This study describes the gender differences found in victims of bullying and work-related stress in an Italian case series and analyzes the critical issues in the diagnostic workup. METHODS: Between 2001 and 2009 we examined 345 outpatients (148 males, 197 females; mean age: 41 +/- 10.49) for suspected psychopathological work-related problems. Diagnosis of bullying was established using international criteria (ICD-10 and DSM-IV). RESULTS: After interdisciplinary diagnostic evaluation (Occupational Medicine Unit, Psychology and Psychiatry Service), the diagnosis of bullying was formulated in 35 subjects, 12 males and 23 females (2 cases of Post-Traumatic Stress Disorder and 33 of Adjustment Disorder). Fifty-four (20 males, 34 females) suffered from work-related anxiety, while work-unrelated Adjustment Disorder and other psychiatric disorders were diagnosed in 7 and 112 subjects, respectively. Women between 34 and 45 years showed a high prevalence (65%) of "mobbing syndrome" or other work-related stress disorders. CONCLUSIONS: At work, women are more subject to harassment (for personal aspects related to emotional and relational factors) than men. The knowledge of the phenomenon is an essential requisite to contrast bullying; prevention can be carried out only through effective information and training of workers and employers, who have the legal obligation to preserve the integrity of the mental and physical status of their employees during work. PMID- 22088164 TI - Obesity predicts primary health care visits: a cohort study. AB - The objective of this study was to explore the relationship between body mass index (BMI), its association with chronic disease, and its impact on health services utilization in the province of Newfoundland and Labrador, Canada, from 1998 to 2002. A data linkage study was conducted involving a provincial health survey linked to 2 health care use administrative databases. The study population comprised 2345 adults between the ages of 20 and 64 years. Self-reported height and weight measures and other covariates, including chronic diseases, were obtained from a provincial survey. BMI categories include: normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), obese class I (BMI 30-34.9), obese class II (BMI >= 35), and obese class III (BMI >= 40). Survey responses were linked with objective physician and hospital health services utilization over a 5-year period. Weight classifications in the study sample were as follows: 37% normal, 39% overweight, 17% obese, and 6% morbidly obese. The obese and morbidly obese were more likely to report having serious chronic conditions after adjusting for age and sex. Only the morbidly obese group (BMI >= 35 kg/m(2)) had a significantly higher number of visits to a general practitioner (GP) over a 5 year period compared to the normal weight group (median 22.0 vs. 17.0, P<0.05). Using multivariate models and controlling for the number of chronic conditions and other relevant covariates, being morbidly obese remained a significant predictor of GP visits (P<0.001), but was not a predictor for visits to a specialist or any type of hospital use. The increase in the prevalence of obesity is placing a burden at the primary health care level. More resources are needed in order to support GPs in their efforts to manage and treat obese adults who have associated comorbidities. PMID- 22088165 TI - The Promoting Effective Advance Care for Elders (PEACE) randomized pilot study: theoretical framework and study design. AB - Practice guidelines are available for hospice and palliative medicine specialists and geriatricians. However, these guidelines do not adequately address the needs of patients who straddle the 2 specialties: homebound chronically ill patients. The purpose of this article is to describe the theoretical basis for the Promoting Effective Advance Care for Elders (PEACE) randomized pilot study. PEACE is an ongoing 2-group randomized pilot study (n=80) to test an in-home interdisciplinary care management intervention that combines palliative care approaches to symptom management, psychosocial and emotional support, and advance care planning with geriatric medicine approaches to optimizing function and addressing polypharmacy. The population comprises new enrollees into PASSPORT, Ohio's community-based, long-term care Medicaid waiver program. All PASSPORT enrollees have geriatric/palliative care crossover needs because they are nursing home eligible. The intervention is based on Wagner's Chronic Care Model and includes comprehensive interdisciplinary care management for these low-income frail elders with chronic illnesses, uses evidence-based protocols, emphasizes patient activation, and integrates with community-based long-term care and other community agencies. Our model, with its standardized, evidence-based medical and psychosocial intervention protocols, will transport easily to other sites that are interested in optimizing outcomes for community-based, chronically ill older adults. PMID- 22088166 TI - Is there clinical benefit to routine enzyme testing of patients on statins? AB - OBJECTIVE: Statin-treated patients undergo frequent laboratory tests. This study evaluated the clinical impact of abnormal liver or muscle enzyme results. RESEARCH DESIGN AND METHODS: This clinical process evaluation study took place in six primary care clinics in Israel. Four hundred and eight patients (average age 63.8 +/- 10.9 years) undergoing statin treatment, with at least one enzyme level > 10% normal, were categorized by symptomatology possibly related to statins. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and creatine phosphokinase were measured. Management and etiology of the elevation were assessed. MAIN OUTCOME MEASURES: Changes in statin regimen. RESULTS: Thirty six (8.8%) patients were symptomatic at the index encounter. One enzyme was elevated in 74.8%. Patients experiencing side effects had more repeat tests (36.1 vs 17.7%, p < 0.001). Musculoskeletal symptoms resulted in a change in treatment more than digestive symptoms did (73.3 vs 16.7%, p < 0.001). Of 40 (9.8%) patients who had additional evaluation, two symptomatic patients had treatment changes. CONCLUSIONS: There is little practical value in routine follow-up enzyme tests for patients on statins. Our findings strengthen reports that recommend muscle and liver enzyme tests for symptomatic patients only. PMID- 22088167 TI - Validation of a rapid and sensitive routine method for determination of chloramphenicol in honey by LC-MS/MS. AB - Chloramphenicol (CAP) is a broad spectrum antibiotic used in the treatment of human and animal diseases. However, CAP can exhibit toxic effects in certain susceptible individuals, causing bone marrow depression, including fatal aplastic anemia. As this condition is dose-independent, CAP has been banned for use in food-producing animals, including honeybees. In this study, a quick, simple and low-cost routine analytical method was developed for the screening and confirmation of chloramphenicol in honey by LC-MS/MS. Sample clean-up takes only two steps without SPE procedure and with recoveries >97%. Honey samples were selected from several producers in Brazil and diluted in a small amount of water. After fortification and addition of d (s)-chloramphenicol as internal standard, the samples were extracted with ethyl acetate. Complete validation of the method was performed on the basis of EU decision 2002/657. Within-laboratory CV reproducibility at the lowest concentration was <10%. An evaluation of two different methods to calculate the decision limit and detection capability gave 0.08 ug kg(-1) for CCalpha and 0.12 ug kg(-1) for CCbeta. PMID- 22088168 TI - Using audit to enhance quality of maternity care in resource limited countries: lessons learnt from rural Tanzania. AB - BACKGROUND: Although clinical audit is an important instrument for quality care improvement, the concept has not yet been adequately taken on board in rural settings in most resource limited countries where the problem of maternal mortality is immense. Maternal mortality and morbidity audit was established at Saint Francis Designated District Hospital (SFDDH) in rural Tanzania in order to generate information upon which to base interventions. METHODS: Methods are informed by the principles of operations research. An audit system was established, all patients fulfilling the inclusion criteria for maternal mortality and severe morbidity were reviewed and selected cases were audited from October 2008 to July 2010. The causes and underlying factors were identified and strategic action plans for improvement were developed and implemented. RESULTS: There were 6572 deliveries and 363 severe maternal morbidities of which 36 women died making institutional case fatality rate of 10%. Of all morbidities 341 (94%) had at least one area of substandard care. Patients, health workers and administration related substandard care factors were identified in 50% - 61% of women with severe morbidities. Improving responsiveness to obstetric emergencies, capacity building of the workforce for health care, referral system improvement and upgrading of health centres located in hard to reach areas to provide comprehensive emergency obstetric care (CEmOC) were proposed and implemented as a result of audit. CONCLUSIONS: Our findings indicate that audit can be implemented in rural resource limited settings and suggest that the vast majority of maternal mortalities and severe morbidities can be averted even where resources are limited if strategic interventions are implemented. PMID- 22088169 TI - Development of industrially feasible concentrated 30% and 40% nanoemulsions for intravenous drug delivery. AB - Emulsions for parenteral nutrition loaded with drugs are used for optimized drug delivery, but in case of poorly oil soluble drugs, the injection volume can be too large when using commercial 10-20% oil emulsions. To reduce the injection volume, the feasibility of producing injectable, physically stable concentrated emulsions up to 40% oil content was investigated. Emulsions were made from fish oil, stabilized with egg lecithin, using high-pressure homogenization. Emulsions with oil contents of 10%-40% were investigated to assess basic correlations between increasing oil content, applied production pressures, homogenization cycles and resulting bulk droplet size, content of larger particles, zeta potential, viscosity and short-term stability. The observed correlations showed that in high-pressure homogenization, the contribution of the dispersive effect dominated the coalescence effect at low and Optimum production conditions for 30% and 40% nanoemulsions, i.e. 800 bar and 2 -3 homogenization cycles, were established on lab scale. These production conditions are industrially feasible. The obtained droplet sizes (about 200 nm) and the content of larger droplets were comparable to 10% commercial emulsions of parenteral nutrition, being important for in vivo tolerability and organ distribution. Despite the high oil concentration, the viscosity of the nanoemulsions was sufficiently low for injection. The short-term storage study showed physical stability for 1 month. A concentrated nanoemulsion base formulation from regulatory accepted excipients is now available, ready for loading with drugs. PMID- 22088170 TI - Rational design of a dual chemosensor for cyanide anion sensing based on dicyanovinyl-substituted benzofurazan. AB - A dicyanovinyl-substituted benzofurazan derivative (C1) was prepared as an efficient ratiometric chemosensor for cyanide anion detection in aqueous acetonitrile solution. Mechanism studies suggested that the nucleophilic addition of cyanide to the alpha-position of the dicyanovinyl group blocked the ICT progress of C1 and induced remarkable emission and absorption shift. PMID- 22088172 TI - Heterogeneous diffusion in thin polymer films as observed by high-temperature single-molecule fluorescence microscopy. AB - Single-molecule fluorescence microscopy was used to investigate the dynamics of perylene diimide (PDI) molecules in thin supported polystyrene (PS) films at temperatures up to 135 degrees C. Such high temperatures, so far unreached in single-molecule spectroscopy studies, were achieved using a custom-built setup which allows for restricting the heated mass to a minimum. This enables temperature-dependent single-molecule fluorescence studies of structural dynamics in the temperature range most relevant to the processing and to applications of thermoplastic materials. In order to ensure that polymer chains were relaxed, a molecular weight of 3000 g/mol, clearly below the entanglement length of PS, was chosen. We found significant heterogeneities in the motion of single PDI probe molecules near T(g). An analysis of the track radius of the recorded single-probe molecule tracks allowed for a distinction between mobile and immobile molecules. Up to the glass transition temperature in bulk, T(g,bulk), probe molecules were immobile; at temperatures higher than T(g,bulk) + 40 K, all probe molecules were mobile. In the range between 0 and 40 K above T(g,bulk) the fraction of mobile probe molecules strongly depends on film thickness. In 30-nm thin films mobility is observed at lower temperatures than in thick films. The fractions of mobile probe molecules were compared and rationalized using Monte Carlo random walk simulations. Results of these simulations indicate that the observed heterogeneities can be explained by a model which assumes a T(g) profile and an increased probability of probe molecules remaining at the surface, both effects caused by a density profile with decreasing polymer density at the polymer-air interface. PMID- 22088171 TI - Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells. AB - INTRODUCTION: The induced pluripotent stem cell (iPSC) technology allows generation of patient-specific pluripotent stem cells, thereby providing a novel cell-therapy platform for severe degenerative diseases. One of the key issues for clinical-grade iPSC derivation is the accessibility of donor cells used for reprogramming. METHODS: We examined the feasibility of reprogramming mobilized GMP-grade hematopoietic progenitor cells (HPCs) and peripheral blood mononuclear cells (PBMCs) and tested the pluripotency of derived iPS clones. RESULTS: Ectopic expression of OCT4, SOX2, KLF4, and c-MYC in HPCs and PBMCs resulted in rapid iPSC derivation. Long-term time-lapse imaging revealed efficient iPSC growth under serum- and feeder-free conditions with frequent mitotic events. HPC- and PBMC-derived iPS cells expressed pluripotency-associated markers, including SSEA 4, TRA-1-60, and NANOG. The global gene-expression profiles demonstrated the induction of endogenous pluripotent genes, such as LIN28, TERT, DPPA4, and PODXL, in derived iPSCs. iPSC clones from blood and other cell sources showed similar ultrastructural morphologies and genome-wide gene-expression profiles. On spontaneous and guided differentiation, HPC- and PBMC-derived iPSCs were differentiated into cells of three germ layers, including insulin-producing cells through endodermal lineage, verifying the pluripotency of the blood-derived iPSC clones. CONCLUSIONS: Because the use of blood cells allows minimally invasive tissue procurement under GMP conditions and rapid cellular reprogramming, mobilized HPCs and unmobilized PBMCs would be ideal somatic cell sources for clinical-grade iPSC derivation, especially from diabetes patients complicated by slow-healing wounds. PMID- 22088174 TI - [Pay attention to the progress in pediatric rheumatic diseases in China]. PMID- 22088173 TI - Tracking iridium atoms with electron microscopy: first steps of metal nanocluster formation in one-dimensional zeolite channels. AB - Using aberration-corrected scanning transmission electron microscopy (STEM), we imaged iridium atoms in isolated iridium complexes in the one-dimensional nonintersecting 14-ring channels of zeolite SSZ-53. STEM allows tracking of the movement of atoms in the channels, demonstrating the interaction of iridium with the zeolite framework (channel confinement) and providing a direct visualization of the initial steps of metal nanocluster formation. The results demonstrate how STEM can be used to help design improved catalysts by identifying the catalytic sites and observing how they change in reactive atmospheres. PMID- 22088175 TI - [Ethic review of clinical researches in children]. PMID- 22088176 TI - [Respiratory syncytial virus infection in hematopoietic stem cell transplantation recipients with primary immunodeficiencies]. AB - OBJECTIVE: To understand the clinical characteristics and outcome associated with respiratory syncytial virus (RSV) infection in hematopoietic stem cell transplantation (HSCT) recipients with primary immunodeficiencies (PIDs). METHOD: Nasopharyngeal aspirate samples were collected consecutively before and after HSCT from 9 recipients from Apr. 2009 to Sep. 2010 and analyzed for the presence of RSV using real-time polymerase chain reaction assay. To further verify the presence of the virus, positive samples for PCR were isolated for RSV. RSV G gene was amplified, sequenced and used for phylogenetic analysis. RESULT: The presence of RSV was detected in 3 out of 9 children. The viral replication in all the patients was prolonged for months. All the 3 patients with RSV infection were treated with intravenous immune globulin (IVIG) and one was treated with antiviral medication. All patients survived and achieved successful immune reconstitution. CONCLUSION: This study indicates that the HSCT recipients with PID are at increased risk for RSV infection. RSV can shed for months after the initial infection and the patients recover with the course of immune reconstitution. PMID- 22088177 TI - [Significance of detecting the EBV-DNA level in peripheral blood mononuclear cells and the EBV-infected cell type in patients with chronic active EBV infection]. AB - OBJECTIVE: To study the difference in the EBV-DNA level in peripheral blood mononuclear cells (PBMC) and the type of Epstein-Barr virus (EBV)-infected cells in pediatric patients with chronic active EBV (CAEBV) infection, acute EBV infection (AEBV) and healthy children, and to analyze the relationship between the above difference and the clinical manifestation of CAEBV. METHOD: Real-time fluorescent quantitative polymerase chain reaction (PCR) was used to detect the EBV-DNA levels in peripheral blood mononuclear cells (PBMC) in 12 normal children, 10 pediatric patients with CAEBV infection and 13 pediatric patients with AEBV infection in our hospital between March 2004 and April 2008. Immunomagnetic bead cell fractionation and fluorescent in situ hybridization (FISH) by EBV encoding RNA-1 ( EBER-1) probe were used in the healthy children, EBV-DNA positive CAEBV patients and AEBV patients to detect the type of EBV infected cells. RESULT: The average EBV-DNA level in CAEBV patients' PBMC was (6.8 x 10(7) +/- 1.1 x 10(8)) copies/ml, while the average EBV-DNA level of AEBV patients' PBMC was (1.3 x 10(6) +/- 1.6 x 10(6)) copies/ml. The average EBV-DNA level of CAEBV infected patients' PBMC was significantly higher than that of AEBV infected patients' PBMC (P<0.01). The cell fractionation and FISH in seven CAEBV patients showed that EBV in CAEBV patients infected not only B cells, but NK cells and CD4+ and CD8+ T cells to different degree, and these patients presented recurrent and persistent infectious mononucleosis (IM)-like symptoms. In 6 CAEBV patients infection mainly occurred to T cells, in one case, infection occurred mainly in CD8+ T cells, and the patient died from fulminant and deadly T lymphocytes proliferative syndrome except presenting firstly high fever, enlargment of the liver, spleen, lymphnode and the severe decrease of one or three kinds of blood cells. In 1 CAEBV patient the infection was mainly found in NK cells, who presented with hypersensitivity to mosquito biting and high IgE level (2500 U/ml). But EBV in seven AEBV patients infection was found only in B cells who presented with only IM for one time and no EBV-infected PBMC were found in the remaining 6 healthy children. CONCLUSION: There are much more EBV replications and different EBV-infected cell types in CAEBV patients. Detection of EBV-DNA level by real-time fluorescent quantitative PCR and the detection of the type of EBV-infected cells may help in diagnosis, treatment and development evaluation of children with CAEBV infection. PMID- 22088178 TI - [Evaluation of therapeutic effects of three hypoallergenic formulae in infants with cow's milk protein allergy]. AB - OBJECTIVE: To compare the growth and symptom remission of infants with cow's milk protein allergy, who were fed with an amino acid formula, an extensively hydrolyzed formula or soy formula. METHOD: Infants who were diagnosed as cow's milk protein allergy and can not be breastfed were enrolled in the intervention group, and were assigned to three special formulae (amino acid formula, extensively hydrolyzed formula or soy formula ) according to the will of parents from March 2009 to March 2010 (n = 74). A non-randomized control group was made up of age-matched healthy children (n = 21). Anthropometric measurements and symptoms were evaluated after 30, 60, 90, and 180 days. The differences of physical growth and the therapeutic effects among each group were calculated by SPSS 13.0 package. RESULT: After 180 days follow-up, the weight for age Z score and length for weight Z score were -0.43 +/- 0.88 and -0.31 +/- 0.78 in patients fed with soy formula substitute, which were significantly lower than those of patients fed with amino acid formula (0.11 +/- 0.77, 0.20 +/- 0.69) , extensively hydrolyzed formula (0.10 +/- 0.62, 0.18 +/- 0.70) and control group (0.22 +/- 0.54, 0.22 +/- 0.64) (P<0.05). However, there were no significant differences in physical growth among patients fed with amino acid formula, extensively hydrolyzed formula and control group (P>0.05). Moreover, no significant difference was found in length for age and head circumference for age among four groups (P>0.05). All hypoallergenic formulae were much helpful in remission of the symptoms of eczema (P<0.05). However, amino acid formula and extensively hydrolyzed formula were more effective and rapid in relieving symptoms than soy formula (1 mo vs 2 mo) (P = 0.003). CONCLUSION: Both amino acid formula and extensively hydrolyzed formula can maintain the normal growth of infants with cow's milk protein allergy. While, the growth of patients fed with soy formula was significantly slower than that of the other three groups. All hypoallergenic formulae can be effective in relieving allergy symptoms, and amino acid formula or extensively hydrolyzed formula seems to be superior to soy formula. PMID- 22088179 TI - [SGI-PS-CMA evidence-based recommendations for the diagnosis and management of juvenile systemic lupus erythematosus]. PMID- 22088180 TI - [The explanation of SGI-PS-CMA evidence-based recommendations for the diagnosis and management of juvenile systemic lupus erythematosus]. PMID- 22088181 TI - [Progress in treatment of juvenile idiopathic arthritis with biologic agents]. PMID- 22088182 TI - [Progress of research on late preterm infants]. PMID- 22088183 TI - [Application of proteomic techniques in pediatric research]. PMID- 22088184 TI - [Summary of national meeting on pediatric immunology in 2010]. PMID- 22088185 TI - [Incidence, diagnosis and treatment of children's congenital abnormalities of the kidney and urinary tract detected in ultrasound screening]. AB - OBJECTIVE: To investigate the proportion of children with congenital abnormalities of the kidney and urinary tract (CAKUT) among those who received screening, analyze the rate, diagnosis and treatment of each abnormality, and evaluate the value of ultrasonography in the CAKUT diagnosis. METHOD: Totally 489 of 26 989 children who received screening for urinary tract abnormalities were found to have CAKUT and were followed up by telephone interviews and were asked whether they had defined diagnosis of CAKUT, had clinical symptoms and received treatment. Children who had been operated on were also asked about the operation time, surgical procedure, postoperative diagnosis, and outcome. Children who had never been reviewed or still had no diagnosis were arranged to Beijing Children's Hospital for ultrasound follow-up. The final data were summed up for a retrospective analysis. RESULT: 1) The proportion of children with CAKUT was 1.67%. Most children with CAKUT had no clinical manifestations. 2) Of the 489 cases, 320 were followed up, and 169 were lost. Of the cases who were followed up, 16 out of 295 cases who had clear diagnosis showed inconsistent results in ultrasound screening. 3) Hydronephrosis was identified in 137 cases (0.78%), among whom 111 were males and 26 were females, in 98 cases the hydronephrosis was on the left, in 28 on the right and in 11 were bilateral. Ureterovesical junction obstruction occurred in 33 cases (0.19%), 25 males and 8 females, in 22 cases on the left, in 10 on right and bilateral in 1 case. Renal dysplasia was shown in 30 cases (0.17%), 22 males and 8 females; renal cysts in 26 cases (0.15%); duplex kidney in 24 cases (0.14%); solitary kidney in 22 cases (0.12%); ureterocele in 16 cases (0.09%); fused kidney in 10 cases (0.06%); renal hypoplasia in 9 cases (0.05%); ectopic kidney in 5 cases (0.03%); polycystic kidney in 3 cases (0.02%). Primary vesicoureteral reflux, posterior urethral valves, renal malrotation, branch renal pelvis, extrarenal pelvis in 1 case each. 4) Totally 114 of the 295 cases (38.6%) who were followed up for CAKUT in screening test required surgical treatment. Only one case of ureteropelvic junction obstruction (UPJO) failed in surgery. CONCLUSION: The proportion of children with CAKUT was high. CAKUT is difficult to detect since there is no significant clinical manifestations in early ages. More than one third of patients with CAKUT needed surgical treatment. Ultrasonography showed obvious advantages in detecting children's CAKUT, proven to be the most preferred method of screening, thus could be recommended as a routine of children's physical examination. PMID- 22088186 TI - [Analysis of clinical manifestations of hospitalized children infected with seasonal influenza A virus and 2009 novel influenza A (H1N1) virus in Beijing]. AB - OBJECTIVE: The novel influenza A (H1N1) virus firstly detected in April 2009 in Mexico rapidly spread to many countries including the United States and Canada where humans were infected with the H1N1 virus and deaths were reported. The pandemic virus strain had never been detected in specimen of human beings and swine. It was so highly contagious and widely spread that threatened life of humans globally. This study aimed to analyze clinical data of hospitalized children patients with 2009 novel H1N1 influenza A virus infection confirmed by etiologic tests, and compared with that of seasonal influenza A. METHOD: Clinical manifestations, laboratory and therapy data from the hospitalized children were collected by designed case report form and analyzed. All patients were enrolled from Capital Institute of Pediatrics from January 2003 to 2010. There were 152 cases in seasonal influenza A group, which was composed of 100 boys and 52 girls. Other 93 boys and 86 girls formed 2009 novel influenza A group. RESULT: Influenza A was dominate from 2003 to 2008 and the peak season was December and January, while the peak hospitalized time of 2009 novel H1N1 influenza was from November 2009 to January 2010. The median age of seasonal influenza group was 35 months, which was lower than that of novel influenza group (Z = -6.702, P<0.01). Besides, 80.9% of the patients in seasonal influenza group were infants, while the novel influenza A group was mainly composed of infants and pre-school children (chi2 = 40.725, P<0.01). The cases of both groups had influenza-like symptoms at onset and the most common presentations were fever and cough. The duration of fever was much longer in 2009 novel influenza group (Z = -7.173, P<0.01). Patients in two groups nearly had the same symptoms except cough was more frequently presented by novel influenza A group cases (chi2 = 4.109, P<0.05). In laboratory examination, the novel influenza group had more cases with abnormality in blood platelet, CRP, ALT, and CK-MB than that of seasonal influenza group (chi2 = 7.562, 17.245, 4.398, 6.217, P<0.01). Patients in novel influenza A group had more changes in electrocardiogram (chi2 = 24.461, P<0.01). More patients had common underlying medical condition in novel influenza groups than those in seasonal influenza group (chi2 = 12.553, P<0.01). Furthermore, the groups had different age distribution in underlying medical diseases (chi2 = 7.231, P<0.05). Children with 2009 novel H1N1 virus infection tended to catch pneumonia (chi2 = 8.661, P<0.01) and became the severe cases (chi2 = 10.595, P<0.01). They had much higher ICU admission rate (chi2 = 12.873, P<0.01) and longer hospital stay (Z = -2.764, P<0.01). CONCLUSION: As a new variant of influenza virus A, 2009 novel H1N1 influenza A had stronger pathogenicity. Children with underlying medical conditions had the high risk to be infected and developed severe manifestations. PMID- 22088187 TI - [Analysis of clinical characteristics and antimicrobial resistance of carbapenem resistant Acinetobacter baumannii infections in children]. AB - OBJECTIVE: This study aimed to summarize the clinical characteristics and antimicrobial resistance of carbapenem-resistant Acinetobacter baumannii (CRAB) infections in children, identify its risk factors and to raise the level of diagnosis and treatment of this disease. METHOD: The data of clinical and antimicrobial susceptibility of 32 cases of CRAB and 64 cases of carbapenem susceptible Acinetobacter baumannii (CSAB) infections as control seen between January 1, 2004 and December 31, 2010 in Yuying Children's Hospital Affiliated to Wenzhou Medical College were analyzed retrospectively. RESULT: Thirty-two cases of CRAB infections were identified, 21 were male and 11 female. The ages ranged from 1 day to 16 years (median age 43 days) ,among whom 14 (44%) were aged < or = 28 days; 28 cases (88%) were diagnosed as hospital-acquired pneumonia (HAP) and 4 cases (12%) had wound infection. The common primary diseases of the cases were neonatal respiratory distress syndrome (n = 12, 38%), followed by congenital heart disease (n = 5,16%) and open fractures (n = 5,16%). Before the isolation of CRAB, 10 cases (31%) had received major surgery;29 patients (91%) had stayed in ICUs, 26 cases (81%) had received tracheal intubation and mechanical ventilation,the ventilation time was 2 -249 days (median: 12 days). Carbapenem was used in 17 cases (53%) previously, 13 (41%) had received beta-lactam/beta lactamase inhibitor combinations, 8 (25%) had used 3rd-generation cephalosporins within 2 weeks before the isolation of CRAB. Sixteen cases (50%) were cured, 12 cases (38%) were improved, parents of 1 case(3%) automatically gave up hospitalization without being cured and 3 cases (9%) died. Forty-nine CRAB strains were isolated from the 32 cases, accounting for 10. 4% of AB isolation strains in the same period, in which 40 strains (82%) were isolated from sputum specimens and 9 strains (18%) from open wounds secretions. All 49 strains showed multidrug-resistance (MDR), of which 13 strains (27%) were pandrug-resistant (PDR) to the common antimicrobials. The rates of resistance to ampicillin sulbactam and cephalosporins were 90% and more than 85%, respectively; while the rates of resistance to cefoperazone-sulbactam were 19%, the lowest among the tested agents. In multivariate analysis, receiving surgery (OR = 8.450), tracheal intubation and mechanical ventilation for more than 10 days (OR = 6.366) and previous use of carbapenems (OR = 7.084) were independent risk factors for CRAB infections. CONCLUSION: Nosocomial infections in children due to CRAB infections mainly cause HAP and open wound infection. Previous surgery, prolonged tracheal intubation and mechanical ventilation for more than 10 days and previous carbapenems therapy within 2 weeks before the isolation of CRAB were independent risk factors for CRAB infections. CRAB showed MDR or even PDR to the common antimicrobials, which made great difficulties in antibiotic choices. PMID- 22088188 TI - [Visceral leishmaniasis associated hemophagocytic lymphohistiocytosis: report of four childhood cases]. AB - OBJECTIVE: The clinical features of four cases of visceral leishmaniasis (VL) associated hemophagocytic lymphohistiocytosis (VL-HLH) were retrospectively analyzed for the purpose of helping the diagnosis of secondary HLH. METHOD: Clinical data of three childhood cases of VL-HLH documented in our hospital and one case diagnosed in the Capital Institute of Pediatrics was reviewed retrospectively, with particular emphasis on peculiar clinical manifestations and on clues to the diagnosis of this relatively rare disease entity. RESULT: Three children were from endemic areas of VL, and the other one had lived in endemic area for one year, which was revealed by detailed history-taking. Clinically, VL HLH is characterized by persistent fever, hepatosplenomegaly and pancytopenia, which is similar to those of HLH, and is one of the important reasons of delayed diagnosis or misdiagnosis. Based on the HLH-2004 protocol, all the four cases met the diagnostic criteria of HLH. In addition, bone marrow aspirate and immunologic detection of VL-specific antibody via rk39 dipstick test during the early disease course of VL-HLH yielded negative results. Two cases who received HLH-targeted therapy responded reasonably well, with rapid temperature normalization and spleen retraction. Nevertheless, Hb remained lower than normal, which we believed to be related to persistent red cell destruction by the invading parasite Leishmania donovani. CONCLUSION: VL, a parasitic disease caused by Leishmania donovani, which is currently endemic just in 6 provinces in China, shares similar clinical picture of HLH and is an easily ignored underlying cause of secondary HLH. We suggest that VL should be in the list of differential diagnosis for any patients with HLH who lives in or has a definite travel history to endemic areas. Repeated bone marrow studies are highly warranted to make a definite diagnosis of VL, because bone marrow aspirate or rk39 dipstick test during early disease course might yield negative results. Although VL-HLH responds quite well to HLH tailored chemotherapy, specific therapy against VL must be given to prevent disease recurrence, and HLH-targeted chemotherapy might be discontinued to prevent chemotherapy-related toxicities. PMID- 22088189 TI - [Clinical and pathological analysis of minimal change nephrotic syndrome in a child with type 1 diabetes]. PMID- 22088190 TI - [One case report of Patau syndrome]. PMID- 22088191 TI - [Mitochondrial ATP synthase deficiency due to 8993T > G mutation on ATP6 gene]. PMID- 22088192 TI - Characterization of lignin by gas chromatography and mass spectrometry using a simplified CuO oxidation method. AB - An efficient and high-throughput method to characterize lignin in environmental samples using alkaline CuO oxidation and capillary gas chromatography with mass detection is presented. Monomeric lignin phenols released during oxidation were selectively extracted using a polymer-based solid phase sorbent rather than liquid phase extraction. Sample size and matrix were found to influence lignin phenol yields. Increasing the sample size to an organic carbon content >=1.5 mg of C minimizes phenol oxidation losses, and the addition of glucose as a sacrificial carbon source helped minimize oxidation losses in samples with <5 mg of organic carbon. PMID- 22088193 TI - Evidence that thaxtomin C is a pathogenicity determinant of Streptomyces ipomoeae, the causative agent of Streptomyces soil rot disease of sweet potato. AB - Streptomyces ipomoeae is the causal agent of Streptomyces soil rot of sweet potato, a disease marked by highly necrotic destruction of adventitious roots, including the development of necrotic lesions on the fleshy storage roots. Streptomyces potato scab pathogens produce a phytotoxin (thaxtomin A) that appears to facilitate their entrance into host plants. S. ipomoeae produces a less-modified thaxtomin derivative (thaxtomin C) whose role in pathogenicity has not been examined. Here, we cloned and sequenced the thaxtomin gene cluster (txt) of S. ipomoeae, and we then constructed targeted txt mutants that no longer produced thaxtomin C. The mutants were unable to penetrate intact adventitious roots but still caused necrosis on storage-root tissue. These results, taken in context with previous histopathological study of S. ipomoeae infection, suggest that thaxtomin C plays an essential role in inter- and intracellular penetration of adventitious sweet potato roots by S. ipomoeae. Once inside the plant host, the pathogen uses one or more yet-to-be-determined factors to necrotize root tissue, including that of any storage roots it encounters. PMID- 22088194 TI - Identification and characterization of tomato mutants affected in the Rx-mediated resistance to PVX isolates. AB - Five tomato mutants affected in the Rx-mediated resistance against Potato virus X (PVX) were identified by screening a mutagenized population derived from a transgenic, Rx1-expressing 'Micro-Tom' line. Contrary to their parental line, they failed to develop lethal systemic necrosis upon infection with the virulent PVX-KH2 isolate. Sequence analysis and quantitative reverse-transcription polymerase chain reaction experiments indicated that the mutants are not affected in the Rx1 transgene or in the Hsp90, RanGap1 and RanGap2, Rar1 and Sgt1 genes. Inoculation with the PVX-CP4 avirulent isolate demonstrated that the Rx1 resistance was still effective in the mutants. In contrast, the virulent PVX-KH2 isolate accumulation was readily detectable in all mutants, which could further be separated in two groups depending on their ability to restrict the accumulation of PVX-RR, a mutant affected at two key positions for Rx1 elicitor activity. Finally, transient expression of the viral capsid protein elicitor indicated that the various mutants have retained the ability to mount an Rx1 mediated hypersensitive response. Taken together, the results obtained are consistent with a modification of the specificity or intensity of the Rx1 mediated response. The five Micro-Tom mutants should provide very valuable resources for the identification of novel tomato genes affecting the functioning of the Rx gene. PMID- 22088195 TI - The aquaporin TcAQP1 of the desert truffle Terfezia claveryi is a membrane pore for water and CO(2) transport. AB - Terfezia claveryi is a hypogeous mycorrhizal fungus belonging to the so-called "desert truffles," with a good record as an edible fungus and of considerable economic importance. T. claveryi improves the tolerance to water stress of the host plant Helianthemum almeriense, for which, in field conditions, symbiosis with T. claveryi is valuable for its survival. We have characterized cDNAs from T. claveryi and identified a sequence related to the aquaporin gene family. The full-length sequence was obtained by rapid amplification of cDNA ends and was named TcAQP1. This aquaporin gene encoded a functional water-channel protein, as demonstrated by heterologous expression assays in Saccharomyces cerevisiae. The mycorrhizal fungal aquaporin increased both water and CO(2) conductivity in the heterologous expression system. The expression patterns of the TcAQP1 gene in mycelium, under different water potentials, and in mycorrhizal plants are discussed. The high levels of water conductivity of TcAQP1 could be related to the adaptation of this mycorrhizal fungus to semiarid areas. The CO(2) permeability of TcAQP1 could be involved in the regulation of T. claveryi growth during presymbiotic phases, making it a good candidate to be considered a novel molecular signaling channel in mycorrhizal fungi. PMID- 22088196 TI - Role of the sucrose synthase encoding PrSus1 gene in the development of the parasitic plant Phelipanche ramosa L. (Pomel). AB - Phelipanche ramosa L. (Pomel) is a major root-parasitic weed attacking many important crops. Success in controlling this parasite is rare and a better understanding of its unique biology is needed to develop new specific control strategies. In the present study, quantitative polymerase chain reaction experiments showed that sucrose synthase encoding PrSus1 transcripts accumulate at their highest level once the parasite is connected to the host (tomato) vascular system, mainly in the parasite tubercles, which bear numerous adventitious roots. In situ hybridization experiments revealed strong PrSus1 expression in both shoot and root apices, especially in shoot apical meristems and in the vascular tissues of scale leaves and stems, and in the apical meristems and developing xylem in roots. In addition, immunolocalization experiments showed that a sucrose synthase protein co-localized with cell-wall thickening in xylem elements. These findings highlight the role of PrSus1 in the utilization of host-derived sucrose in meristematic areas and in cellulose biosynthesis in differentiating vascular elements. We also demonstrate that PrSus1 is downregulated in response to 2,3,5-triiodobenzoic acid-induced inhibition of polar auxin transport in the host stem, suggesting that PrSus1 activity in xylem maturation is controlled by host-derived auxin. PMID- 22088198 TI - [Giant perineal tumour]. PMID- 22088199 TI - [New method of hepatic regeneration]. AB - Postoperative liver failure (PLF) is the most feared and serious complication after extensive liver resections. We present an innovative surgical technique for the treatment of a patient with colorectal cancer and initially unresectable liver metastases. After completing neoadjuvant chemotherapy, it was decided to perform simultaneous surgery. A left hemicolectomy and cleaning of the metastases in the left liver was performed. As the future liver remnant (FLR) was insufficient, it was decided to perform an in situ liver split and a right portal vein ligation. On the 6(th) day after the surgery a volumetric CT showed an increase greater than 40% of the FLR. The right hepatectomy was completed and the patient was discharged on the 11(th) day after surgery. The technique induced a rapid growth of the FLR, exceeding that reported using portal occlusion. If these findings are corroborated in future studies, this revolutionary technique could enable surgery to be performed in two stages on patients with initially unresectable liver disease during the same hospital admission and without PLF. PMID- 22088197 TI - The biology and dynamics of mammalian cortical granules. AB - Cortical granules are membrane bound organelles located in the cortex of unfertilized oocytes. Following fertilization, cortical granules undergo exocytosis to release their contents into the perivitelline space. This secretory process, which is calcium dependent and SNARE protein-mediated pathway, is known as the cortical reaction. After exocytosis, the released cortical granule proteins are responsible for blocking polyspermy by modifying the oocytes' extracellular matrices, such as the zona pellucida in mammals. Mammalian cortical granules range in size from 0.2 um to 0.6 um in diameter and different from most other regulatory secretory organelles in that they are not renewed once released. These granules are only synthesized in female germ cells and transform an egg upon sperm entry; therefore, this unique cellular structure has inherent interest for our understanding of the biology of fertilization. Cortical granules are long thought to be static and awaiting in the cortex of unfertilized oocytes to be stimulated undergoing exocytosis upon gamete fusion. Not till recently, the dynamic nature of cortical granules is appreciated and understood. The latest studies of mammalian cortical granules document that this organelle is not only biochemically heterogeneous, but also displays complex distribution during oocyte development. Interestingly, some cortical granules undergo exocytosis prior to fertilization; and a number of granule components function beyond the time of fertilization in regulating embryonic cleavage and preimplantation development, demonstrating their functional significance in fertilization as well as early embryonic development. The following review will present studies that investigate the biology of cortical granules and will also discuss new findings that uncover the dynamic aspect of this organelle in mammals. PMID- 22088200 TI - Usefulness of two-dimensional echocardiographic parameters of the left side of the heart to predict right ventricular failure after left ventricular assist device implantation. AB - Right ventricular failure (RVF) after left ventricular assist device (LVAD) placement is associated with increased morbidity and mortality. Echocardiography is a primary imaging method in the assessment of cardiac function; however, visualization of the right-sided heart is often technically difficult in patients with heart failure. We aimed to create a simple and generally applicable scoring system based on "left-sided echocardiographic parameters" to provide complementary information for predicting RVF after LVAD surgery. We reviewed 111 consecutive patients undergoing LVAD surgery from 2007 through 2010. Echocardiograms within 5 days before surgery were analyzed. RVF was defined as an unexpected RV assist devices requirement, nitric oxide inhalation >48 hours, and/or inotropic support >14 days. Thirty-five patients (32%) developed RVF. LV end-diastolic dimension (LVEDD) was smaller, LV ejection fraction was greater, and the left atrial diameter/LVEDD ratio was greater (p < 0.05 for all comparisons) in patients with RVF than in those without RVF. An RVF score (LV echocardiographic RVF score) was determined as a sum of points based on receiver operator characteristics analysis: LVEDD >78, 79 to 70, and <70 mm; LV ejection fraction <=19%, 19% to 33%, and >33%; and left atrial diameter/LVEDD <0.63, 0.63 to 0.68, and >0.68; each variable was associated with 0 and 1 point and 2 points, respectively. LV echocardiographic RVF score >=3 was associated with RVF with a sensitivity of 88.6% and score >=5 with a specificity of 80.3%. In conclusion, patients with relatively small LV size, preserved LV contraction, and dilated left atrium were at higher risk for RVF after LVAD surgery. In conclusion, LV echocardiographic RVF score provides a novel tool to predict RVF after LVAD surgery, which does not involve invasive or technically complicated procedures. PMID- 22088201 TI - Comparison of outcomes of patients with painless versus painful ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention. AB - There are few data available on the prognosis of painless ST-segment elevation myocardial infarction (STEMI). The aim of this study was to determine the incidence, clinical characteristics, and outcomes of painless STEMI. We analyzed the Korea Acute Myocardial Infarction Registry (KAMIR) study, which enrolled 7,288 patients with STEMI (61.8 +/- 12.8 years old, 74% men; painless STEMI group, n = 763; painful STEMI group, n = 6,525). End points were in-hospital mortality and 1-year major adverse cardiac events (MACEs). Patients with painless STEMI were older and more likely to be women, nonsmokers, diabetic, and normolipidemic and to have a higher Killip class. The painless group had more in hospital deaths (5.9% vs 3.6%, p = 0.026) and 1-year MACEs (26% vs 19%, p = 0.002). In Cox proportional hazards analysis, hypotension (hazard ratio [HR] 4.40, 95% confidence interval [CI] 1.41 to 13.78, p = 0.011), low left ventricular ejection fraction (HR 3.12, 95% CI 1.21 to 8.07, p = 0.019), and a high Killip class (HR 3.48, 95% CI 1.19 to 10.22, p = 0.023) were independent predictors of 1-year MACEs in patients with painless STEMI. In conclusion, painless STEMI was associated with more adverse outcomes than painful STEMI and late detection may have contributed significantly to total ischemic burden. These results warrant more investigations for methodologic development in the diagnosis of silent ischemia and painless STEMI. PMID- 22088202 TI - Nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase (AMPK). AB - The objective of this study was to elucidate the effect of nobiletin (5,6,7,8,3',4'-hexamethoxyflavone) on adipogenesis in 3T3-L1 cells. To determine the effect of nobiletin on adipogenesis, preadipocyte differentiation was induced in the presence or absence of nobiletin (10-100 MUM) for 4 days. The results revealed that nobiletin markedly inhibited lipid accumulation and glycerol-3 phosphate dehydrogenase (GPDH) activity and blocked the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptors (PPARgamma) and CCAAT/enhancer binding proteins (C/EBPalpha). Moreover, nobiletin significantly increased AMP-activated protein kinase (AMPK), a major regulator of cellular energy balance, phosphorylation, and intracellular reactive oxygen species (ROS) generation. This study also investigated the involvement of AMPK in the expression of a major transcription factor, PPARgamma. It was found that pretreatment with compound C, a cell permeable inhibitor of AMPK, abolished the inhibitory effects of nobiletin on PPARgamma expression. The results suggest that nobiletin exerts antiadipogenic effects through modulation of the PPARgamma and AMPK signaling pathway and, therefore, may be a promising antiobesity agent. PMID- 22088203 TI - Exposures to transit and other sources of noise among New York City residents. AB - To evaluate the contributions of common noise sources to total annual noise exposures among urban residents and workers, we estimated exposures associated with five common sources (use of mass transit, occupational and nonoccupational activities, MP3 player and stereo use, and time at home and doing other miscellaneous activities) among a sample of over 4500 individuals in New York City (NYC). We then evaluated the contributions of each source to total noise exposure and also compared our estimated exposures to the recommended 70 dBA annual exposure limit. We found that one in ten transit users had noise exposures in excess of the recommended exposure limit from their transit use alone. When we estimated total annual exposures, 90% of NYC transit users and 87% of nonusers exceeded the recommended limit. MP3 player and stereo use, which represented a small fraction of the total annual hours for each subject on average, was the primary source of exposure among the majority of urban dwellers we evaluated. Our results suggest that the vast majority of urban mass transit riders may be at risk of permanent, irreversible noise-induced hearing loss and that, for many individuals, this risk is driven primarily by exposures other than occupational noise. PMID- 22088204 TI - Low-molecular-weight heparins induce decidual heparin-binding epidermal growth factor-like growth factor expression and promote survival of decidual cells undergoing apoptosis. AB - OBJECTIVE: To evaluate the effects of low-molecular-weight heparins (LMWHs) on decidual heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression/secretion and on TNF-alpha-induced decidual apoptosis. DESIGN: Experimental study. SETTING: Department of Obstetrics and Gynecology, Universita Cattolica del Sacro Cuore, Rome, Italy. PATIENT(S): Cultures of primary decidual cells isolated from human term placenta. INTERVENTION(S): The effects of LMWHs (tinzaparin and enoxaparin) on decidual HB-EGF expression and secretion were investigated by Western blot analysis and ELISA, respectively. TNF-alpha-induced decidual apoptosis was evaluated by annexin V staining, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay, and caspase activities. MAIN OUTCOME MEASURE(S): Decidual HB-EGF expression/secretion and apoptotic rate induced by TNF-alpha were investigated. RESULT(S): Tinzaparin enhanced decidual HB-EGF expression and secretion. TNF-alpha reduced the number of viable cells by inducing apoptosis. Simultaneous addition of LMWHs (primarily tinzaparin) blocked the increase in annexin V- and TUNEL-positive cells and reduced the amount of caspase activities. CONCLUSION(S): Both LMWHs induced a significant increase in decidual HB-EGF expression/secretion and reduced TNF alpha-induced decidual apoptosis. Tinzaparin demonstrated higher efficacy. PMID- 22088205 TI - Bilateral oophorectomy is not associated with increased mortality: the California Teachers Study. AB - OBJECTIVE: To investigate the effect of surgical menopause due to bilateral oophorectomy on mortality, in light of evidence that bilateral oophorectomy among premenopausal women rapidly reduces endogenous hormone levels, thereby modifying risks of cardiovascular disease and breast cancer. DESIGN: The California Teachers Study (CTS) is a prospective cohort study of 133,479 women initiated in 1995-1996 through a mailed, self-administered questionnaire. Relative risks and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. SETTING: None. PATIENT(S): California Teachers Study participants who, at baseline, reported having surgical menopause due to bilateral oophorectomy (n = 9,785), were compared with participants with natural menopause (n = 32,219). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We investigated whether bilateral oophorectomy was associated with all-cause, cardiovascular, or cancer mortality, overall and by menopausal hormone therapy use status. RESULT(S): Among participants aged <45 years at menopause, multivariable relative risks were 0.86 (95% CI, 0.74-1.00), 0.85 (95% CI, 0.66-1.11), and 0.91 (95% CI, 0.67-1.23) for all-cause mortality, cardiovascular mortality, and cancer mortality, respectively. Among participants with an age at menopause of >=45 years, multivariable relative risks were 0.87 (95% CI, 0.80-0.94), 0.83 (95% CI, 0.71-0.96), and 0.84 (95% CI, 0.72-0.98) for all-cause, cardiovascular, and cancer mortality, respectively. The association between bilateral oophorectomy and mortality did not differ by baseline status of hormone therapy use. CONCLUSION(S): Surgical menopause due to bilateral oophorectomy vs. natural menopause does not increase all-cause, cardiovascular, or cancer mortality. PMID- 22088206 TI - Improvement of hyperandrogenism and hyperinsulinemia during pregnancy in women with polycystic ovary syndrome: possible effect in the ovarian follicular mass of their daughters. AB - OBJECTIVE: To evaluate the ovarian function during early infancy in daughters of women with polycystic ovary syndrome (PCOS) treated with metformin throughout pregnancy (PCOSd+M), as a means to reduce androgen and insulin levels, compared with daughters of nontreated PCOS women (PCOSd-M) and daughters of women who belong to a healthy comparison group (HCd). DESIGN: Descriptive and analytic study. SETTING: Unit of endocrinology and reproductive medicine. PATIENT(S): Fifteen PCOSd+M, 23 PCOSd-M, and 35 HCd were studied at 2-3 months of age. INTERVENTION(S): A GnRH analogue test was performed with determinations of gonadotropins, sex steroids, SHBG, and anti-Mullerian hormone (AMH). MAIN OUTCOME MEASURE(S): Differences in AMH levels between PCOSd+M, PCOSd-M and HCd. RESULT(S): AMH and peak E(2) concentrations were significantly higher in PCOSd-M compared with HCd, whereas PCOSd+M exhibited AMH concentrations and peak E(2) levels similar to those observed in HCd. CONCLUSION(S): The improvement of the altered endocrine-metabolic environment of PCOS mothers reduces AMH levels in their daughters, which might reflect a decrease in their follicular mass. PMID- 22088207 TI - Intracytoplasmic sperm injection in partial globozoospermia. AB - OBJECTIVE: To compare the outcome of intracytoplasmic sperm injection (ICSI) in patient couples where the male partner has partial globozoospermia with the outcome in a general ICSI population. DESIGN: Case-control study. SETTING: Center for Reproductive Medicine, Radboud University Nijmegen Medical Center, the Netherlands, a tertiary referral center. PATIENT(S): Between 1997 and 2005, 42 couples were identified in which the male presented with partial globozoospermia; 27 couples treated with ICSI were matched with 263 control couples from a general ICSI population regarding female age and year of first ICSI cycle. INTERVENTION(S): One ICSI treatment (1-10 ICSI cycles). MAIN OUTCOME MEASURE(S): Live birth rate after one ICSI treatment (1-10 ICSI cycles). RESULT(S): In the partial globozoospermia group, the live birth rate was 66.7% compared with 50.0% in the control group. In partial globozoospermia, three out of 21 pregnancies ended in a miscarriage, one major birth defect occurred, and one pregnancy ended in a neonatal death due to sepsis in a premature child, compared with four stillborn in the control group. CONCLUSION(S): ICSI is an effective treatment in couples that failed to conceive spontaneously within 1 year combined with male infertility due to partial globozoospermia. The fertilization rates and the live birth rates in this specific group did not differ from those of the general ICSI population. PMID- 22088208 TI - Proteomic approach in the identification of fertility pattern in seminal plasma of fertile men. AB - OBJECTIVE: To identify a panel of common seminal proteins in human seminal plasma by fertile men that might be involved in successful reproduction. DESIGN: Experimental study. SETTING: University hospital. PATIENT(S): Five fertile men who conceived within 3 months before the start of the study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proteomic analysis performed by an Ultimate 3000 Nano/Micro-HPLC apparatus equipped with an FLM-3000-Flow manager module and coupled with an LTQ Orbitrap XL hybrid mass spectrometer; gene ontology analysis. RESULT(S): From 919 to 1,487 unique proteins were identified per individual subject sample. Among these proteins, 83 proteins were present in all samples, including some proteins that might be involved in male fertility, such as semenogelin I, semenogelin II, olfactory receptor 5R1, lactoferrin, hCAP18, spindling, and clusterin. The gene ontology annotation analysis provided further information in describing common pattern in male fertility. CONCLUSION(S): The identification of common seminal plasma proteome in fertile men could provide better insight into the physiology of male fertility and might identify novel markers of male infertility. PMID- 22088209 TI - The ART of social networking: how SART member clinics are connecting with patients online. AB - OBJECTIVE: To study and describe the use of social networking websites among Society for Assisted Reproductive Technology (SART) member clinics. DESIGN: Cross sectional study. SETTING: University-based practice. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Prevalence of social networking websites among SART member clinics and evaluation of content, volume, and location (i.e., mandated state, region) using multivariate regression analysis. RESULT(S): A total of 384 SART-registered clinics and 1,382 social networking posts were evaluated. Of the clinics, 96% had a website and 30% linked to a social networking website. The majority of clinics (89%) with social networking websites were affiliated with nonacademic centers. Social networking posts mostly provided information (31%) and/or advertising (28%), and the remaining offered support (19%) or were irrelevant (17%) to the target audience. Only 5% of posts involved patients requesting information. Clinic volume correlated with the presence of a clinic website and a social networking website. CONCLUSION(S): Almost all SART member clinics have a website. Nearly one-third of these clinics host a social networking website such as Facebook, Twitter, and/or a blog. Large-volume clinics commonly host social networking websites. These sites provide new ways to communicate with patients, but clinics should maintain policies on the incorporation of social networks into practice. PMID- 22088210 TI - Phosphoproteomic analysis of human mesenchymal stromal cells during osteogenic differentiation. AB - Human mesenchymal stromal cells (hMSCs) are promising candidates for cell therapy and tissue regeneration. Knowledge of the molecular mechanisms governing hMSC commitment into osteoblasts is critical to the development of therapeutic applications for human bone diseases. Because protein phosphorylation plays a critical role in signaling transduction network, the purpose of this study is to elucidate the phosphoproteomic changes in hMSCs during early osteogenic lineage commitment. hMSCs cultured in osteogenic induction medium for 0, 1, 3, and 7 days were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Surprisingly, we observed a dramatic loss of protein phosphorylation level after 1 day of osteogenic induction. Pathways analysis of these reduced phosphoproteins exhibited a high correlation with cell proliferation and protein synthesis pathways. During osteogenic differentiation, differentially expressed phosphoproteins demonstrated the dynamic alterations in cytoskeleton at the early stages of differentiation. The fidelity of our quantitative phosphoproteomic analyses were further confirmed by Western blot analyses, and the changes from protein expression or its phosphorylation level were distinguished. In addition, several ion channels and transcription factors with differentially expressed phosphorylation sites during osteogenic differentiation were identified and may serve as potentially unexplored transcriptional regulators of the osteogenic phenotype of hMSCs. Taken together, our results have demonstrated the dynamic changes in phosphoproteomic profiles of hMSCs during osteogenic differentiation and unraveled potential candidates mediating the osteogenic commitment of hMSCs. The findings in this study may also shed light on the development of new therapeutic targets for metabolic bone diseases such as osteoporosis and osteomalacia. PMID- 22088211 TI - Intravascular large B-cell lymphoma presenting as slowly progressive paraparesis with normal MRI features. AB - Intravascular large B-cell lymphoma (IVLBCL) is a rare, high grade extranodal B cell lymphoma, characterized by the proliferation of tumoral cells in the lumen of small vessels of several organs without the tendency for tumor formation in other areas usually affected by lymphomas, such as lymph nodes, bone marrow, or peripheral blood. Diagnosis is generally delayed by variable presentation with non-specific constitutional and neurological symptoms, lack of reliable ancillary tests and it is often obtained only at autopsy. We report a case of IVLBCL presenting with a slowly progressing isolated paraparesis without any evidence of spinal damage at MRI though neurophysiological examinations showed signs of spinal cord injury. Laboratory findings showed markedly elevated levels of lactate dehydrogenase, low albumin values, raised ESR, mild thrombocytopenia and progressive impairment of hepatic function. Bone marrow examinations and total body CT scans were negative. Although clinical history appeared too long, we considered the hypothesis of IVLBCL on the basis of the laboratory constellation and proposed a liver biopsy, but the patient refused the procedure. The diagnosis was confirmed only at autopsy. Our case should make us aware that the disease has to be considered in the differential diagnosis of unexplained paraparesis associated with elevated level of lactate dehydrogenase and only relatively non specific laboratory findings even without any spinal cord abnormalities at MRI. PMID- 22088212 TI - Misfolded SOD1 forms high-density molecular complexes with synaptic molecules in mutant SOD1-linked familial amyotrophic lateral sclerosis cases. AB - Mutations in the superoxide dismutase 1 (sod1) gene cause familial amyotrophic lateral sclerosis (FALS), likely due to the toxic properties of misfolded mutant SOD1 protein. Here we report identification of various synaptic molecules forming molecular complexes with misfolded SOD1 in mutant SOD1-associated FALS patient tissues as well as in cellular FALS models. In the FALS cellular model system, we found that membrane depolarization that mimics synaptic hyperactivation/excitotoxicity could cause misfolding of mutant SOD, as well as acceleration of misfolded SOD1-synaptic protein complex formation. These results suggest that inhibition of synaptic release mechanism by association of misfolded SOD1 with synaptic molecules plays a role in the dysfunction of FALS. PMID- 22088213 TI - Low levels of diversity among genomes of Porcine circovirus type 1 (PCV1) points to differential adaptive selection between Porcine circoviruses. AB - Several features related with the evolutionary patterns among all the PCV1 genomes available at GenBank have been analyzed in the present work (diversity, number of genotypes, recombination, saturation, selection, evolutionary rate). The reported results point to low levels of nucleotide and amino acid diversity, low number of positively selected codons and a slow evolution rate. Compared with the other species of the Circoviridae family, the diversity is the lowest reported. This can be related with the fact that PCV1 is the single non pathogenic member of the family. Overall, differential levels of adaptive evolution between PCV1 and PCV2 may explain the different diversity levels, and the different evolutionary and selection rates observed. PMID- 22088214 TI - Identification and classification of endogenous retroviruses in the canine genome using degenerative PCR and in-silico data analysis. AB - Pooled genomic DNA from 10 dogs was subjected to polymerase chain reaction with primers targeting the retroviral pro/pol region. Sequence analysis of 120 clones obtained by PCR revealed 81 of retroviral origin. Subsequent analysis of the dog genome (CanFam 2.0) by BLAST investigation using degenerate PCR products and previously identified retroviral sequences permitted the identification of additional retroviral gamma and beta sequences. A phylogenetic analysis using the retroviral protease (PR) and reverse transcriptase (RT) sequences in the dog genome resulted in identification of 17 gamma and 7 beta families. In addition, we also identified 167 spuma-like ERV elements from CanFam 2.0 based on sequence homology to murine (Mu)ERV-L and human (H)ERV-L. Our results could contribute to the understanding of the influence of retroviruses in shaping the genome structure and altering gene expression by providing quantitative and locational information of ERV loci and their diversity in the dog genome. PMID- 22088215 TI - Sequence analysis of 12 genome segments of mud crab reovirus (MCRV). AB - Mud crab reovirus (MCRV) is the causative agent of a serious disease with high mortality in cultured mud crab (Scylla serrata). This study sequenced and analyzed 12 genome segments of MCRV. The 12 genome segments had a total length of 24.464 kb, showing a total G+C content of 41.29% and predicted 15 ORFs. Sequence analysis showed that the majority of MCRV genes shared low homology with the counterpart genes of other reoviruses, e.g., the amino acid identity of RNA dependent RNA polymerase (RdRp) was lower than 13.0% compared to the RdRp sequences of other reoviruses. Nucleotide and amino acid sequences of RdRp and capping enzyme suggested MCRV as a single group. Further genome-based phylogenetical analysis of conserved termini and reovirus polymerase motif indicates that this MCRV belongs to a new genus of the Reoviridae family, tentatively named as Crabreovirus. PMID- 22088216 TI - The N-terminal helix alpha(0) of hepatitis C virus NS3 protein dictates the subcellular localization and stability of NS3/NS4A complex. AB - The N-terminal amphipathic helix alpha(0) of hepatitis C virus (HCV) NS3 protein is an essential structural determinant for the protein membrane association. Here, we performed functional analysis to probe the role of this helix alpha(0) in the HCV life cycle. A point mutation M21P in this region that destroyed the helix formation disrupted the membrane association of NS3 protein and completely abolished HCV replication. Mechanistically the mutation did not affect either protease or helicase/NTPase activities of NS3, but significantly reduced the stability of NS3 protein. Furthermore, the membrane association and stability of NS3 protein can be restored by replacing the helix alpha(0) with an amphipathic helix of the HCV NS5A protein. In summary, our data demonstrated that the amphipathic helix alpha(0) of NS3 protein determines the proper membrane association of NS3, and this subcellular localization dictates the functional role of NS3 in the HCV life cycle. PMID- 22088218 TI - Investigational VEGF antagonists for psoriasis. AB - INTRODUCTION: Vascular endothelial growth factor (VEGF) mediates angiogenesis consequent to binding to VEGF receptors (VEGFRs) and is upregulated in patients with psoriasis. VEGF is also upregulated in other diseases characterised by angiogenesis including proliferative retinopathy and cancer. Several VEGF antagonists have been approved for the treatment of these conditions and may also have the potential to treat psoriasis. AREAS COVERED: A PubMed literature search was performed to identify preclinical and clinical research regarding investigational VEGF antagonists for the treatment of psoriasis. Various agents have been reviewed including monoclonal antibodies against VEGF and VEGFRs, decoy anti-VEGF receptors and tyrosine kinase inhibitors that block the effects of VEGF/VEGFR binding. EXPERT OPINION: Several investigational drugs have demonstrated potential to treat psoriasis. Clinical observations of psoriasis remission following administration of bevacizumab, sunitinib and sorafenib in cancer patients are encouraging. Of particular interest is a novel anti-VEGF/anti TNF-alpha decoy receptor (Valpha), whose dual action could be beneficial given the numerous pathogenetic pathways in psoriasis. A topical tyrosine kinase inhibitor also has potential given the cost and safety advantages conferred by this mode of administration. More research is warranted both in the prototypical drugs and in those already marketed for other indications. PMID- 22088217 TI - Cholesterol-rich lipid rafts are required for release of infectious human respiratory syncytial virus particles. AB - Cholesterol and sphingolipid enriched lipid raft micro-domains in the plasma membrane play an important role in the life-cycle of numerous enveloped viruses. Although human respiratory syncytial virus (RSV) proteins associate with the raft domains of infected cells and rafts are incorporated in RSV virion particles, the functional role of raft during RSV infection was unknown. In the current study we have identified rafts as an essential component of host cell that is required for RSV infection. Treatment of human lung epithelial cells with raft disrupting agent methyl-beta-cyclodextrin (MBCD) led to drastic loss of RSV infectivity due to diminished release of infectious progeny RSV virion particles from raft disrupted cells. RSV infection of raft deficient Niemann-Pick syndrome type C human fibroblasts and normal human embryonic lung fibroblasts revealed that during productive RSV infection, raft is required for release of infectious RSV particles. PMID- 22088219 TI - Muscarinic receptor activation determines the effects of store-operated Ca(2+) entry on excitability and energy metabolism in pyramidal neurons. AB - In various cell types, depletion of intracellular Ca(2+)-stores results in store operated Ca(2+)-entry (SOCE) across the cellular membrane. However, the effects of SOCE on neuronal membrane excitability and mitochondrial functions in central neurons are not well defined. We investigated such cellular downstream effects in pyramidal neurons of rat organotypic hippocampal slice cultures by applying electrophysiological and fluorescence imaging techniques. We report that SOCE is associated with (i) elevations of Ca(2+)-concentration in individual neuronal mitochondria ([Ca(2+)](m)). In addition, SOCE can result in (ii) hyperpolarizing neuronal membrane currents, (iii) increase in extracellular K(+)-concentration ([K(+)](o)), (iv) mitochondrial membrane depolarization, and (v) changes in intracellular redox state (NAD(P)H and FAD fluorescence), the latter reflecting responses of energy metabolism. These additional downstream effects of SOCE required concomitant muscarinic receptor activation by carbachol or acetylcholine, and were suppressed by agonist washout or application of antagonist, atropine. We conclude that muscarinic receptor activation determines the downstream effects of SOCE on neuronal membrane excitability and energy metabolism. This mechanism might have significant impact on information processing and neurometabolic coupling in central neurons. PMID- 22088221 TI - Winning the war, far, in developing countries. Novel anticoagulants as a new weapon against stroke. PMID- 22088220 TI - Regional imbalanced activation of the calcineurin/BAD apoptotic pathway and the PI3K/Akt survival pathway after myocardial infarction. AB - BACKGROUND: The underlying molecular mechanisms of the remodeling after myocardial infarction (MI) remain unclear. The purpose of this study was to investigate the role of a survival pathway (PI3K/Akt) and an apoptosis pathway (calcineurin/BAD) in the remodeling after MI in a large animal model. METHODS: Ten Dorset hybrid sheep underwent 25% MI in the left ventricle (LV, n=10). Five sheep were used as sham control. The regional strain was calculated from sonomicrometry. Apoptosis and the activation of the PI3K/Akt and calcineurin/BAD pathways were evaluated in the non-ischemic adjacent zone and the remote zone relative to infarct by immunoblotting, immunoprecipitation, and immunofluorescence staining. RESULTS: Dilation and dysfunction of LV were present at 12 weeks after MI. The regional strain in the adjacent zone was significantly higher than in the remote zone at 12 weeks (36.6 +/- 4.0% vs 9.5 +/- 3.6%, p<0.05). Apoptosis was more severe in the adjacent zone than in the remote zone. The PI3K/Akt and calcineurin/BAD pathways were activated in the adjacent zone. Dephosphorylation and translocation of BAD were evident in the adjacent zone. Regional correlation between the strain and the expression of calcineurin/BAD indicated that the activation was strain-related (R(2)=0.46, 0.48, 0.39 for calcineurin, BAD, mitochondrial BAD, respectively, p<0.05). CONCLUSIONS: The PI3K/Akt survival and calcineurin/BAD apoptotic pathways were concomitantly activated in the non-ischemic adjacent zone after MI. The calcineurin/BAD pathway is strain related and its imbalanced activation may be one of the causes of progressive remodeling after MI. PMID- 22088222 TI - Mortality of patients with ST-segment elevation myocardial infarction and cardiogenic shock treated by PCI is correlated to the infarct-related artery- results from the PL-ACS Registry. AB - BACKGROUND: Mortality of patients with ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock (CS) on admission remains high despite invasive treatment. The aim of this analysis was to assess the relationship between the infarct-related artery (IRA) and the early and 12-month outcomes of patients with STEMI and CS treated by percutaneous coronary intervention (PCI). METHODS: Two thousand ninety patients with STEMI and CS registered in the prospective Polish Registry of Acute Coronary Syndromes from October 2003 to November 2009 were included. RESULTS: The in-hospital mortality in the left main (LM), left anterior descending artery (LAD), circumflex artery (Cx), and right coronary artery (RCA) groups was 64.7%, 41.0%, 36.0%, and 30.8%, respectively, with p<0.0001. The 12 month mortality in the LM, LAD, Cx, and RCA groups was 77.7%, 58.2%, 55.1%, and 45.0%, respectively, with p<0.0001. After multivariate adjustment, LM as the IRA was significantly associated with higher 12-month mortality (hazard ratio=1.71, 95% confidence interval=1.28-2.27, p=0.0002). CONCLUSIONS: In-hospital and long term mortality of patients with STEMI and CS treated by PCI are significantly correlated to the IRA, being highest for LM and lowest for RCA. PMID- 22088223 TI - Right lung agenesis and dextrocardia in a paucisymptomatic 11-year-old child. PMID- 22088225 TI - How to manage coronary slow flow following PCI? PMID- 22088224 TI - Adiposity rather than BMI determines metabolic risk. AB - BACKGROUND AND AIM: There is increasing evidence suggesting that WHO body mass index (BMI) cut-off values are outdated and should not be applied to different population. To overcome misclassifications, direct measurements of percentage body fat (PBF) would be a better tool for preobesity and obesity diagnosis. The aim of this study was to analyze the body composition in a adult population in Centre-South of Italy, by age and gender, and to verify the accordance between BMI and PBF cut-off points for health status classification. METHODS: The total subject pool cover a total of 4408 participants adults. A completed screening of anthropometry and body composition by Dual X-ray Absorptiometry, (DXA) was assessed on 3.258 subjects. RESULTS: Distributions and quantitative reliable estimates of PBF, total body fat and lean, according to gender and age are provided. The prevalence of "at risk" subjects (preobese and obese) was 69% and 85%, for men and women respectively, according to PBF cut-off points. The agreement of BMI and PBF categories resulted low for the total and male population, even scarce for female population (all P <= 0.001). The false negative classification of BMI was stronger for women than men and for younger than older subjects. CONCLUSIONS: Screening for adiposity in subjects with a normal BMI could better identify those at higher risk for cardiometabolic disturbances and cardiovascular mortality. The herein used cut-offs points of PBF, by age and gender, may provide a useful reference in clinical settings and public health services, in particular for the Italian Caucasian population. PMID- 22088226 TI - Carotid stenting improves cognitive function in asymptomatic cerebral ischemia. AB - OBJECTIVES: Asymptomatic critical internal carotid artery (ICA) stenosis may lead to cognitive impairment. Carotid stenting (CS) may improve cerebral perfusion, but its impact on neuro-cognitive function has been controversial. METHODS: We prospectively enrolled 34 asymptomatic patients with unilateral ICA stenosis or occlusion, in whom CS was attempted. Computed tomography cerebral perfusion (CTP), and functional assessments including National Institutes of Health Stoke Scale (NIHSS), Bathel Index (BI), and a battery of neuropsychological tests including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subtest (ADAS-Cog), verbal fluency, and Color Trail Making A and B, were done prior to and 3 months after the procedure. RESULTS: Successful CS was achieved in 28 of 34 patients (82%). Based on the baseline CTP finding and intervention result, patients were divided into three groups: group I (n=6) as ipsilateral cerebral ischemia with failed CS procedure, group II (n=17) as ipsilateral cerebral ischemia with successful CS procedure, and group III (n=11) as normal baseline CTP with successful CS procedure. The demographics and baseline cognitive performances were similar among the three groups. In group II, there were significant improvement in Alzheimer Disease Assessment Scale (pre 6.8 +/- 4.3 vs post 4.9 +/- 2.8, p=0.033), Mini-Mental State Examination Score (pre 25.8 +/- 3.8 vs post 27.4 +/- 3.5, p=0.007), and Color Trail test A (pre 120.4 +/ 73.9s vs post 95.8 +/- 57.6s, p=0.004) after CS. In groups I and III, however, no significant difference was observed in any of the cognitive tests. CONCLUSIONS: Successful CS improves neurocognitive function in asymptomatic ICA stenosis or occlusion with objective ipsilateral ischemia. PMID- 22088227 TI - More data, better data or improved evidence translation: what will improve cardiovascular outcomes? AB - More data, better data or improved evidence translation: what will improve cardiovascular outcomes? As countries must focus more on the value of and access to health services over effectiveness alone, we argue that data on key aspects of interventions are predominantly missing from the current evidence-base. We examine this need in relation to secondary prevention of the most burdensome disease in the world: coronary heart disease and consider the wider forms of evidence about interventions needed by professionals, systems and governments to promote effective, accessible and efficient chronic disease management. PMID- 22088228 TI - Disturbed left atrial mechanical function in paroxysmal atrial fibrillation: a speckle tracking study. AB - OBJECTIVE: We aimed to assess left atrial (LA) intrinsic myocardial function and its relationship to left ventricular (LV) filling pattern in a group of paroxysmal atrial fibrillation (PAF) patients. METHODS: Twenty-three PAF patients (age 68 +/- 7 year, 10 males) were studied using speckle tracking echocardiography and compared with 18 age and sex matched controls. LA segmental longitudinal strain (S), strain rate (SR) and myocardial velocities during atrial systole were measured as were LA diameters. E/A and E/Em were also measured. RESULTS: LA longitudinal diameter was larger in patients (5.5 +/- 0.6 vs. 4.8 +/- 0.6 cm, p<0.01) and global LA S (-9.2 +/- 4.3 vs. -12.9 +/- 4.6%, p=0.01) and SR (-1.1 +/- 0.5 vs. -1.6 +/- 0.7 1/s, p<0.01) were reduced and correlated with E/A (r=0.52, p=0.01 and r=0.43, p<0.05, respectively). LA lateral S and SR were uniformly reduced compared with controls (p<0.05 for all). Both septal and lateral wall SR correlated with E/A (p<0.05 for all), only septal S correlated with E/A (p<0.05). LA myocardial velocities were highest at the annular level and lowest at the rear in both patients and controls (p<0.01 for all). CONCLUSION: In PAF patients, LA systolic function is suppressed and is directly related to the pattern of LV filling which itself may suggest raised pressures. While intrinsic global and segmental function can reproducibly be studied by S and SR, myocardial velocities reflect only regional motion, thus less sensitive in demonstrating localize dysfunction. PMID- 22088229 TI - Human complement Factor H modulates C1q-mediated phagocytosis of apoptotic cells. AB - Complement is implicated in the clearance of apoptotic cells by phagocytes. Deficiencies in early complement components, particularly C1q, are associated with an increased risk of the development of systemic lupus erythematosus. C1q is considered to be important in this process through interaction with apoptotic cells and phagocytes. In the present study, we confirm that apoptotic cells are recognized not only by C1q but also by the complement regulatory protein Factor H. Both C1q and Factor H bind to apoptotic cells in a dose-dependent and saturable manner. We further examined the role of C1q and Factor H in the clearance of apoptotic cells by monocytes. C1q enhanced uptake/adhesion of apoptotic cells by monocytes whereas Factor H alone had no effect on this process. However, when both C1q and Factor H were present on the apoptotic cell surface, C1q-mediated enhancement of uptake/adhesion of the apoptotic cells by monocytes was reduced. This effect of Factor H also occurred if monocytes were pre-treated with Factor H, and then exposed to C1q-coated apoptotic cells. The results were consistent with Factor H interacting with monocytes through the integrin CD11b/CD18. We conclude that under physiological conditions, Factor H may be important in controlling the inflammation which might arise from C1q deposition on apoptotic cells. PMID- 22088230 TI - Glial heterotopia of the orbit: a rare presentation. AB - BACKGROUND: Glial heterotopias are rare, benign, congenital, midline, non teratomatous extracranial glial tissue. They may masquerade as encephalocoele or dermoid cyst and mostly present in nose. Herein, we present an unusual case of glial heterotopia of the orbit with unilateral blindness. CASE PRESENTATION: A 6 year-old-boy presented with a progressive painless mass over the nose and medial aspect of the left eye noticed since birth. On examination, the globe was displaced laterally by a firm, regular, mobile, non-pulsatile and non-tender medial mass. The affected eye had profound loss of vision. Computed tomography scan showed a large hypodense mass in the extraconal space with no intracranial connectivity and bony erosion. The child underwent total surgical excision of the mass and histopathological examination confirmed glial heterotopia of the orbit. CONCLUSION: Though the incidence of this condition is rare, the need of appropriate diagnosis and management of such mass to prevent the visual and cosmetic deterioration is warranted. To our knowledge this is the first reported case of Glial heterotopia of orbit causing unilateral blindness. PMID- 22088231 TI - Coprocessing of cellulose II with amorphous silicon dioxide: effect of silicification on the powder and tableting properties. AB - AIM: In recent years, coprocessing has been the most successful approach to improve and correct the functionality of excipients. The aim of this study is to coprocessed cellulose II with SiO(2) and to evaluate the resulting powder and tableting properties. METHODS: Novel cellulose II:SiO(2) (98:2, 95:5, 90:10 and 80:20 w/w ratios) composites were produced by spray drying, wet granulation and spheronization techniques and the resulting powder and tableting properties were assessed. RESULTS: Cellulose II:SiO(2) composites produced by spray- drying exhibited spherical/oblongate shape, narrow distribution and mean diameter from 51 to 75 um. The composites produced by wet granulation had larger distribution, granular shape and a mean diameter from 105 to 129 um. The spheronized composites showed the highest size (from 148 to 450 um) and round shape. Bulk and tap densities and flow were reduced as the silicification level increased in the spray dried and wet granulated materials. Likewise, silicification increased the true density, porosity and surface roughness of these materials. Water sorption decreased only at silicification level of 20% being comparable to the ones shown by Prosolv((r)) samples. Contact angles of all cellulose II materials were lower than those of cellulose I except for Celphere203 indicating better wettability. A 5% and 10% silicification levels rendered the strongest compacts for the spray dried and wet granulated materials, respectively. Silicification did not affect the fast disintegration properties of MCCII. CONCLUSIONS: Coprocessing proved to be useful tool to modify the powder and tableting properties of cellulose II. PMID- 22088232 TI - [Critical review of the new recommendations on screening for hydroxychloroquine retinopathy]. AB - New recommendations for screening of hydroxychloroquine retinopathy, updating those of 2002, have been recently published by the American Academy of Ophthalmology. These recommendations have been necessary because of new knowledge about the prevalence of toxicity and because of improved screening tools. Amsler grid testing, color vision testing, fluorescein angiography, full-field electroretinogram, and electro-oculogram are no longer recommended. It is now recommended to perform fundus examinations with 10-2 automated fields, and whenever possible, at least one objective test including multifocal electroretinogram, fundus autofluorescence or spectral domain optical coherence tomography (SD-OCT). A baseline examination is advised as a reference and then, annual screening should be initiated no later than 5 years after starting hydroxychloroquine therapy. PMID- 22088233 TI - Maternal valvular heart disease in pregnancy. AB - Valvular heart disease is common in pregnancy. Maternal physiology changes significantly during gestation with substantial increases in cardiac output and blood volume; this can cause unmasking or worsening of cardiac disease. Acquired valvular lesions most frequently arise from rheumatic fever, especially in patients who have emigrated from developing nations. Congenital lesions are also encountered. The most common conditions seen, mitral stenosis and regurgitation and aortic stenosis and regurgitation, each require a specific evaluation and management and are associated with their own set of possible complications. Patients with prosthetic valves require anticoagulation, and maternal and fetal risks and benefits must be carefully weighed. Patients with heart disease should be meticulously managed preconceptionally up to the postpartum period by maternal fetal medicine specialists, obstetricians, cardiologists, and anesthesiologists using a multi-disciplinary approach to their cardiac conditions. TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians. LEARNING OBJECTIVES: After the completing the CME activity, physicians should be better able to examine the epidemiology of valvular heart disease in pregnancy, categorize key physiologic parameters that change in the cardiovascular system during pregnancy, classify the pathophysiology of valvular lesions, and evaluate the general principles of maternal and fetal management for cardiac disease. PMID- 22088234 TI - Ethical concerns and career satisfaction in obstetrics and gynecology: a review of recent findings from the Collaborative Ambulatory Research Network. AB - Obstetricians-gynecologists (ob-gyns) are frequently confronted with situations that have ethical implications (e.g., whether to accept gifts or samples from drug companies or disclosing medical errors to patients). Additionally, various factors, including specific job-related tasks, costs, and benefits, may impact ob gyns' career satisfaction. Ethical concerns and career satisfaction can play a role in the quality of women's health care. This article summarizes the studies published between 2005 and 2009 by the Research Department of the American College of Obstetricians and Gynecologists, which encompass ethical concerns regarding interactions with pharmaceutical representatives and patient safety/medical error reporting, as well as ob-gyn career satisfaction. Additionally, a brief discussion regarding ethical concerns in the ob-gyn field, in general, highlights key topics for the last 30 years. Ethical dilemmas continue to be of concern for ob-gyns. Familiarity with guidelines on appropriate interactions with industry is associated with lower percentages of potentially problematic relationships with pharmaceutical industries. Physicians report that the expense of patient safety initiatives is one of the top barriers for improving patient safety, followed by fear of liability. Overall, respondents reported being satisfied with their careers. However, half of the respondents reported that they were extremely concerned about the impact of professional liability costs on the duration of their careers. Increased familiarity with guidelines may lead to a decreased ob-gyn reliance on pharmaceutical representatives and free samples, whereas specific and practical tools may help them implement patient safety techniques. The easing of malpractice insurance and threat of litigation may enhance career satisfaction among ob-gyns. This article will discuss related findings in recent years. TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians. LEARNING OBJECTIVES: After the completing the CME activity, physicians should be better able to analyze how interactions with pharmaceutical industry may pose ethical dilemmas, examine current barriers to implementing patient safety initiatives, and evaluate the factors that influence career satisfaction among obstetrician-gynecologists. PMID- 22088235 TI - The oldest gravidas: a review of pregnancy risks in women over 45. AB - As a result of delayed childbearing and increasingly sophisticated assisted reproductive technologies, pregnancy in women aged >=45 years is becoming more common. Women in this age-group should receive thorough preconception evaluation and counseling about their specific risks in pregnancy. Although many pregnancies in women >45 years old are achieved via assisted reproductive technologies with associated preconception counseling, as many as 45% may be spontaneously conceived. It is therefore important for obstetrician-gynecologists to incorporate education for older women about the risks of pregnancy into routine office visits, and to ask women in this age-group about pregnancy planning. Additionally, many pregnancies in women aged >45 years may be safely managed in a nontertiary care center, avoiding the need for referral and transfer of care to an unfamiliar setting. This review addresses preconception evaluation and counseling, real and perceived risks in older mothers, common pregnancy complications and management of pregnancy in women >45 years old. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be better able to counsel women about the risks of pregnancy for women aged >=45, evaluate older women for common risk factors that may further increase risk in pregnancy, assess pregnancy complications that are more common in women aged >45, and manage otherwise uncomplicated pregnancies in women in this age-group. PMID- 22088236 TI - Characterisation of the oral, vaginal and rectal Lactobacillus flora in healthy pregnant and postmenopausal women. AB - OBJECTIVE: To investigate the hypothesis that the rectum may be an important reservoir for vaginal colonisation by Lactobacillus species. STUDY DESIGN: We included 60 pregnant women aged 18-35 years and 80 postmenopausal women aged 55 65 years in this cross-sectional observational study. Participants had to be without clinical signs of vaginal infection and without hormone replacement therapy. Only women with normal vaginal microflora (Nugent scores 0-3) were included in the evaluation. The first oral, vaginal, and rectal smears were taken for the enumeration of lactobacilli by cultural methods and identification of dominating lactobacilli based on multiplex polymerase chain reaction (PCR). The second oral, vaginal, and rectal smears were taken for molecular lactobacilli profiling using PCR denaturing gradient gel electrophoresis (DGGE). RESULTS: 30 pregnant and 30 postmenopausal women were evaluated. On multiplex PCR, 99 colonies isolated from 30 pregnant women and 37 colonies isolated from 30 postmenopausal women were identified as being members of the genus Lactobacillus: 50% of pregnant and 33% of postmenopausal women had one or more Lactobacillus spp. recovered from their oral specimens. Around 80% of pregnant and 40% of postmenopausal women harboured one or more Lactobacillus spp. in the vagina and rectum. On PCR-DGGE, 80% of pregnant and 40% of postmenopausal women harboured the same lactobacilli isolates in both the vagina and rectum. CONCLUSION: This study supports the hypothesis that the rectum may play an important role as a reservoir for some strains of lactobacilli that colonise the vagina. PMID- 22088237 TI - Interface engineering by piezoelectric potential in ZnO-based photoelectrochemical anode. AB - Through a process of photoelectrochemical (PEC) water splitting, we demonstrated an effective strategy for engineering the barrier height of a heterogeneous semiconductor interface by piezoelectric polarization, known as the piezotronic effect. A consistent enhancement or reduction of photocurrent was observed when tensile or compressive strains were applied to the ZnO anode, respectively. The photocurrent variation is attributed to a changed barrier height at the ZnO/ITO interface, which is a result of the remnant piezoelectric potential across the interface due to a nonideal free charge distribution in the ITO electrode. In our system, ~1.5 mV barrier height change per 0.1% applied strain was identified, and 0.21% tensile strain yielded a ~10% improvement of the maximum PEC efficiency. The remnant piezopotential is dictated by the screening length of the materials in contact with piezoelectric component. The difference between this time independent remnant piezopotential effect and time-dependent piezoelectric effect is also studied in details. PMID- 22088238 TI - [Take action to lead the prevention and control of non-communicable disease]. PMID- 22088239 TI - [2010 Chinese guidelines for the management of hypertension]. AB - The 2010 Chinese guidelines for the management of hypertension is an update of the previous versions in 2005 and 1999. A guideline committee of nearly 100 members appointed by the Chinese Hypertension League (CHL) and the National Centre for Cardiovascular Disease (NCCD), in collaboration with the Chinese societies of cardiology, nephrology, neurology, gynecology and endocrinology, convened on several occasions and discussed the guidelines, drafted by a core writing group. The prevalence of hypertension has been increasing in China for decades, and reached 18.8% in the year 2002. The rates of awareness, treatment and control for hypertension patients remain low compared to high income countries, in spite of substantial improvements since 1991. In some communities, the control rate of hypertension increased up to 60%. The mortality rate of stroke, which is the major complication of hypertension in the Chinese population, gradually decreased during the period, more so in urban areas than in rural areas for the middle-aged and elderly populations; in the younger age groups, however, it increased. As hypertension is a "cardiovascular syndrome", the management strategy should be based on the overall risk of cardiovascular disease estimated with all related risk factors, target organ damage and co morbidity of patients. The target blood pressure is set at SBP/DBP < 140/90 mm Hg (1 mm Hg = 0. 133 kPa) in uncomplicated hypertension; < 150/90 mm Hg for the elderly (> or = 65 years) or, if tolerable, < 140/90 mm Hg; and < 130/80 mm Hg for those with diabetes, coronary heart disease or renal disease. For these high risk patients, the management should be individualised. In general, lifestyle modification, such as sodium restriction, smoking cessation, moderation of body weight and alcohol consumption, and increasing dietary potassium intake and physical activity, should be implemented for prevention and control of hypertension. Five classes of antihypertensive drugs, including calcium channel blockers, angiotensin converting enzyme inhibitors, angiotensin type II receptor blockers, diuretics and beta-blockers, as well as single pill combinations of these agents, can be used for initial and maintenance of antihypertensive treatment. Several populations require special attention in the prevention and control of hypertension, such as children and adolescents, the elderly, pregnant women, and patients with various cardiovascular complications. Since health-care policies and resources vary substantially from one place to another, two levels of recommendations of management are proposed: a sophisticated and a basic, allowing doctors-in-charge to manage their patients in a more feasible way. PMID- 22088240 TI - [Impact of cytochrome P450 2C19 polymorphisms on outcome of cardiovascular events in clopidogrel-treated Chinese patients after percutaneous coronary intervention]. AB - OBJECTIVE: To investigate the impact of cytochrome P450 (CYP) 2C19 681G > A polymorphism on long-term prognosis of clopidogrel-treated Chinese patients after percutaneous coronary intervention (PCI). METHODS: Between January 1, 2009 and August 31,2009, 267 patients with coronary heart disease who received PCI and treated with clopidogrel for 12 months were enrolled. CYP2C19 * 2 was detected by MALDI-TOF MS and patients were grouped into CYP2C19 * 1/ * 1 (n = 130) and CYP2C19 * 2 carriers group (n = 137). Follow-up was 12 months. The primary endpoint was angina recurrence, urgent coronary revascularization, acute myocardial infarction, stent thrombosis, death and the combined end points. RESULTS: Baseline data were similar between two groups (P > 0.05). Urgent coronary revascularization and the combined end points occurred more frequently in CYP2C19 * 2 carriers than in CYP2C19 * 1/* 1 patients (7.3% vs. 1.5% and 8.0% vs. 2.3% respectively, all P < 0.05). But incidence of angina recurrence, acute myocardial infarction, stent thrombosis and death was similar between two groups (all P > 0.05). Hazard risk of 1 year cumulative survival of CYP2C19 * 2 carriers group was significantly higher than CYP2C19 * 1/ * 1 group after PCI ( HR = 3.59, 95% CI: 1.02 - 12.87, P < 0.05). CONCLUSION: CYP2C19 681G > A polymorphism is a determinant of prognosis in coronary heart disease patients receiving chronic clopidogrel treatment after PCI. PMID- 22088241 TI - [Efficacy of arterial duct stenting in neonatal pulmonary atresia with intact ventricular septum]. AB - OBJECTIVE: To evaluate the feasibility and efficacy of arterial duct stenting in neonates with pulmonary atresia and intact ventricular septum. METHODS: Eleven neonatal pulmonary atresia with intact ventricular septum patients received arterial duct stenting in our hospital from December 2007 to September 2010 were involved in this study. The average age was (8.20 +/- 2.90) days (ranged from 3 to 13 days). The average weight was (3.41 +/- 0.29) kg (ranged from 3.00 to 3.88 kg). The stents were selected according to digital subtracted angiography measurements. After checking for correct position by angiography, the balloon was inflated to expand the stent to desired diameter. Oxygen saturation was monitored, echocardiography was measured and stent diameter and location were observed by chest Xray. Patients were followed up at 1, 3, 6 and 12 months post procedure. RESULTS: Stents were successfully implanted in all 11 patients. The preoperative peripheral oxygen saturation was (63.27 +/- 8.47)%, while increased to (82.73 +/- 5.59)% after alprostadil application and to (86.18 +/- 3.19)% after operation (all P < 0.01). After the operation, the peripheral oxygen saturation was higher than alprostadil application (P < 0.05). The intraoperative narrowest diameter of patent ductus arteriosus was (1.69 +/- 0.37) mm, the length was (16.72 +/- 2.37) mm. The internal diameter of implant stents was 4 mm, the length was (20.18 +/- 3.40) mm. After the operation, surgical B-T shunt operation was performed in one patient due to stent shift and pulse oxygen saturation decrease. One patient died post operation with unknown reason, another patient received stent balloon dilatation due to pulse oxygen saturation decrease at 4 months after the surgery. Pulmonary atresia with intact ventricular septum surgeries were performed in 2 patients at 5 and 7 months after stent implantation. CONCLUSION: The neonatal pulmonary atresia with intact ventricular septum arterial stent implantation was a feasible and effective procedure and this method could be used as preferred treatment in pulmonary atresia and intact ventricular septum for neonates. PMID- 22088242 TI - [Comparison of cryoablation and radiofrequency ablation for treating atrioventricular nodal reentrant tachycardia]. AB - OBJECTIVE: To compare the efficacy and safety between cryoablation (Cryo) and radiofrequency (RF) ablation for treating patients with atrioventricular nodal reentrant tachycardia (AVNRT). METHODS: Patients with AVNRT (n = 304) were divided into Cryo group (n = 67) and RF group (n = 237). The procedure success rate, complete slow pathway block rate, atrioventricular block rate and relapse rate were compared between two groups. RESULTS: There was no statistically difference between 2 groups in the success rate (Cryo group 98.5% vs RF group 97.0%, P = 0.820), complete slow pathway block rate (Cryo group 98.5% vs RF group 91.6%, P = 0.088), atrioventricular block rate (Cryo group 0 vs RF group 2.5%, P = 0.413), relapse rate (Cryo group 0 vs RF group 1.7%, P = 0.643). But Cryo group had more advantage than RF group. CONCLUSION: Efficacy and safety were comparable between cryoablation and radiofrequency ablation for treating patients with AVNRT. PMID- 22088243 TI - [Outcome and factors affecting left atrial remodeling after percutaneous balloon mitral valvuloplasty in patients with mitral valve stenosis]. AB - OBJECTIVE: To observe the outcome and assess related factors affecting left atrial remodeling after percutaneous balloon mitral valvuloplasty (PBMV) in patients with mitral valve stenosis. METHODS: From March 1998 to June 2002, there were 96 mitral valve stenosis patients who underwent PBMV in our hospital. Echocardiographic, 12 leads united electrocardiogram and other clinical datas were collected at preoperation, 1 week after operation, and 4 - 6 years after operation to retrospective analysis. Multiple stepwise regression analysis was used to assess controllable factors of left atrial remodeling. RESULTS: Left atrial diameter reduced from (44.6 +/- 6.6) cm before PBMV to (42.8 +/- 6.5) cm (P > 0.05) 1 week after PBMV and enlarged to (47.2 +/- 5.7)cm (all P < 0.05) at the end of 4 - 6 years follow up post operation. The mitral valve area (MVA) increased from (1.06 +/- 0.32) cm2 before PBMV to (2.02 +/- 0.43) cm2 1 week after PBMV and (1.98 +/- 0.36) cm2 4 - 6 years post operation (all P < 0.05). Heart function assessed by NYHA classification improved significantly at 1 week and 4 - 6 years after surgery compared with pre-operation (P < 0.01). Multiple stepwise regression analysis showed that systolic blood pressure at 4 - 6 years after operation, MVA at 1 week after operation, preoperative atrial fibrillation, Wilkins score < or = 8, preoperative left atrial diameter were the independent predictive factors of left atrial remodeling at 4 - 6 years after PBMV. CONCLUSIONS: PBMV was an effective therapy option for patients with mitral valve stenosis. Systolic blood pressure at 4 - 6 years after operation, MVA at 1 week after operation, preoperative atrial fibrillation, Wilkins < or = 8, preoperative left atrial diameter are the predictive factors of left atrial remodeling after PBMV. PMID- 22088244 TI - [Relationship between 22q11 microdeletion syndrome and congenital heart disease]. AB - OBJECTIVE: To investigate the relationship between 22q11 microdeletion syndrome and congenital heart disease. METHODS: Clinical screening assessment and genetic testing using standard fluorescence in-situ hybridization (FISH) were applied in 207 subjects suspected for 22q11 microdeletion syndrome. Patients with 22q11 microdeletion syndrome were examined by echocardiography, patients with complicated congenital heart disease were examined further by cardiac catheterization. RESULTS: 22q11 microdeletion syndrome was detected in 39 subjects. The incidence of 22q11 microdeletion syndrome was 1.6% in suspects with simple congenital heart disease without extracardiac manifestations, 53.0% in suspects with congenital heart disease combined with at least two extracardiac manifestations, 3.8% in suspects without congenital heart disease. The incidence of congenital heart disease in 22q11 microdeletion syndrome patient and non 22q11 microdeletion syndrome patient was 94.9% and 54.2% (P < 0.01). The incidence of congenital heart disease combined with at least two extracardiac manifestations in 22q11 microdeletion syndrome patient and non 22q11 microdeletion syndrome patient was 89.7% and 18.5% (P < 0.01). In 22q11 microdeletion syndrome patients, Tetralogy of Fallot was the most common type of congenital heart disease. Dysmorphic faces, learning difficulties and retarded physical development were the most common extracardiac manifestations of the congenital heart disease patients. CONCLUSION: 22q11 microdeletion syndrome is related to congenital heart disease. PMID- 22088245 TI - [Effect of different combined antihypertensive regimen on the erectile function in male hypertensive patients]. AB - OBJECTIVE: To compare the effects of felodipine combined irbesartan regimen with that of felodipine combined metoprolol regimen on the sexual function in male hypertensive patients. METHOD: One hundred and twenty-three male hypertensive patients (age 25 to 60) were randomly assigned to felodipine (5 mg/d) plus irbesartan (150 mg/d, n = 64) group and felodipine (5 mg/d) plus metoprolol (47.5 mg/d, n = 59) group. Dosage of felodipine were doubled after 4 weeks if the blood pressure were > or = 140/ 90 mm Hg (1 mm Hg = 0.133 kPa). At the baseline and post 24th week treatment, sexual function of patients was assessed by the International Index of Erectile Function (IIEF) Questionaire. Serum testosterone (T), sex hormone binding globulin (SHBG), 4-hydroxynonenal (HNE), 8-hydroxy-2' deoxyguanosine (8-OHdG) and Malonaldehyde (MDA) were measured by Radioimmunoassay (RIA), ELISA and TBA respectively. RESULTS: Total prevalence of erectile dysfunction (ED), T, SHBG and HNE were similar between pre- and post-treatment in two groups (P > 0.05). On the other hand, the scores of the mild ED and sexual desire (SD) were improved and both serum 8-OHdG and MDA in patients with ED decreased [(146.02 +/- 60.54) ng/L vs. (139.89 +/- 62.03) ng/L, P = 0.048 and (6.59 +/- 1.75) micromol/L vs. (5.51 +/- 1.65) micromol/L, P = 0.039] in Felodipine plus Irbesartan group. CONCLUSION: The results suggested that Felodipine + Irbesartan regimen may be superior to Felodipine + metoprolol regimen for male hypertensive patients with mild ED. PMID- 22088246 TI - [Clinical and angiographic characteristics of patients with slow coronary flow]. AB - OBJECTIVE: To analyze the clinical and angiographic characteristics of patients with slow coronary flow (SCF). METHODS: In this retrospective study, 140 patients with SCF and 140 control subjects without SCF were included. SCF were diagnosed by the combination of TIMI flow grade method and TIMI frame count method. All subjects had angiographically normal coronary arteries. The clinical and laboratory data were obtained from medical records at admission. RESULTS: Compared to control group, patients with SCF were younger [(57.8 +/- 10.7) years vs. (59.8 +/- 8.2) years], rate of smokers (59.3% vs. 46.4%) and diabetes mellitus (49.3% vs. 30.7%), fasting blood glucose (FBG) level [(7.8 +/- 2.8) mmol/L vs. (6.2 +/- 2.0) mmol/L, P < 0.05] and triglyceride (TG) level [(2.11 +/- 1.93) mmol/L vs. (1.67 +/- 1.01) mmol/L, P < 0.05] were higher, while high density lipoprotein cholesterol (HDL-C) level [(1.05 +/- 0.35) mmol/L vs. (1.42 +/- 0.74) mmol/L, P < 0.01] and apolipoprotein A1 (apoA1) level [(1.10 +/- 0.19) mmol/L vs. (1.31 +/- 0.31) mmol/L, P < 0.01] were lower. Among the 140 SCF patients, left anterior descending artery (LAD), left circumflex artery (LCX) and right coronary artery (RCA) were involved at the same time in 92 patients. Among the three vessels, RCA is the most frequent involved vessel (n = 119). After adjusting for other risk factors, current smoking (OR = 1.92, 95% CI: 1.04 - 3.57, P < 0.05), DM history (OR = 2.44, 95% CI:1.32-4.76, P < 0.01), FBG (OR = 2.13, 95% CI:1.16-3.98, P < 0.05), TG (OR = 1.47, 95% CI:1.03-2.13, P < 0.05), HDL-C (OR = 0.47, 95% CI:0.24-0.85, P < 0.05) and apoA1 (OR = 0.55, 95% CI:0.40 - 0.75, P < 0.01) were independent factors for SCF (all P < 0.05). CONCLUSIONS: Our results demonstrated that patients with SCF were prone to have a significant metabolic disorder compared to the control group. Patients with high levels of FBG, TG and low levels of HDL-C were more likely to suffer from SCF, which maybe explained by the development of coronary endothelium and microvascular dysfunction. PMID- 22088247 TI - [Impact of stromal interaction molecule 1 silencing on cell cycle of endothelial progenitor cells]. AB - OBJECTIVE: To investigate the effect of stromal interaction molecule 1 (STIM1) silencing on EPCs cell cycle. METHODS: Rat bone marrow derived endothelial progenitor cells (EPCs) were isolated and cultured in L-DMEM with 20% FBS. Ad si/rSTIM1 and Ad-hSTIM1 were then transfected into EPCs and the expression of STIM1 mRNA was detected by RT-PCR. The cell cycle was determined using flow cytometry analysis and intracellular free Ca2+ was measured using LSCM. Co immunoprecipitation was performed to examine the interaction between STIM1 and TRPC1. Protein levels of inositol 1, 4, 5-trisphosphate were analyzed with ELISA assay. RESULTS: Forty-eight hours after transfection, the expression of STIM1 mRNA was significantly downregulated (0.37 +/- 0.02 vs. 1.00 +/- 0.02, P < 0.05) and intracellular free Ca2+ level was significantly reduced (34.07 +/- 4.10 vs. 86.51 +/- 14.12, P < 0.05) in Ad-si/rSTIM1 group compared with control group. The cell cycle was arrested at G1 phase [(90.91 +/- 1.10)% vs. (77.10 +/- 0.56)%, P < 0.05] and the store-operated channel entry was strikingly inhibited in EPCs after treatment with Ad-si/rSTIM1. However, cotransfection of Ad-hSTIM1 with Ad si/rSTIM1 significantly reversed these responses. Interestingly, co immunoprecipitation study showed that STIM1 co-precipitated with TRPC1, and IP3 levels measured by ELISA were similar among three groups (P > 0.05). CONCLUSION: siRNA-mediated knockdown of STIM1 inhibited EPCs proliferation by reducing intracellular free Ca2+ through TRPC1-SOC signaling pathway. PMID- 22088248 TI - [Impact of magnetic field exposure on cardiac autonomic tone and inducibility of atrial fibrillation in dogs]. AB - OBJECTIVE: To observe the maximal heart rate changes, atrioventricular (A-V) conduction block and atrial fibrillation (AF) inducibility in dogs with vagosympathetic trunk exposed to electromagnetic fields (EMFs). METHODS: The vagosympathetic trunk of adult dogs was separated and exposed to EMFs 0.043 kHz (2.87 microG, n = 5) and to EMFs 2 kHz (0.34 microG, n = 6) for two to three hours. Simultaneously, the vagosympathetic trunk was stimulated with 20 Hz frequency and 1 - 8 V intensity for 0.1 ms. Heart rate, presence of A-V conduction block and AF inducibility were determined. RESULTS: After 5-minutes exposure to EMFs 0.043 kHz (2.87 microG), the maximal heart rate decreased 29%, the voltage applied to vagosympathetic trunk required to induce A-V conduction block decreased by 60% in experimental group versus 5% increase in control group. This effect lasted 2 to 3 hours. While vagosympathetic trunk exposure to EMFs 2 kHz (0.34 microG) was associated with significant increase in the incidence of atrial premature beats, atrial tachycardia and AF, these effects could be blocked by propranolol and atropine. CONCLUSIONS: Our results showed that 0.043 kHz (2.87 microG) EMFs exposure might reduce while 2 kHz (0.34 microG) EMFs exposure might increase AF inducibility. Our study thus suggested autonomic nervous system of dogs could be affected by EMFs exposure and 0.043 kHz (2.87 microG) EMFs exposure might be a novel option for AF prevention. PMID- 22088249 TI - [Effects of telmisartan and pyridoxamine on abdominal aorta vascular remodeling in spontaneously hypertensive rats]. AB - OBJECTIVE: To investigate the effects of telmisartan and pyridoxamine on vascular smooth muscle cells (VSMCs) proliferation and apoptosis as well as abdominal aorta vascular remodeling in spontaneously hypertensive rats (SHRs). METHODS: SHRs randomly received placebo, telmisartan (6 mg kg(-1) x d(-1)), pyridoxamine (200 mg x kg(-1) x d(-1)) or telmisartan (6 mg x kg(-1) x d(-1)) plus pyridoxamine (200 mg x kg(-1) x d(-1), n = 12 each) for 16 weeks. Wistar-Kyoto (WKY, n = 12) rats serve as normotensive control. The systolic blood pressure (SBP) of rat was measured before and weekly thereafter. The serum advanced glycation end-products (AGEs) were detected by competitive ELISA. The serum super oxide dismutase (SOD) and nitric oxide (NO) were measured. The abdominal aorta were assessed by image analysis in HE stained sections. The VSMCs apoptosis and proliferation in abdominal aorta were detected with in situ end labeling technique and proliferating cell nuclear antigen (PCNA) immunohistochemistry staining respectively. RESULTS: SBP were significantly lower in telmisartan and telmisartan plus pyridoxamine therapy group than in placebo treated hypertensive rats while not affected by pyridoxamine (P > 0.05). Activity of SOD and NO were significantly higher and AGEs significantly lower in telmisartan, pyridoxamine and combination therapy treated SHRs than in placebo treated hypertensive rats (P < 0.01). The telmisartan, pyridoxamine and combination therapy can significantly inhibit the PCNA expression and significantly enhance the apoptosis value in abdominal aorta (P < 0.01). The efficacy of combined treatment was significantly higher than telmisartan and pyridoxamine alone (P < 0.05). CONCLUSION: Telmisartan and pyridoxamine could attenuate abdominal aorta vascular remodeling via reducing oxidative stress and AGEs production as well as restoring the balance of VSMCs proliferation and apoptosis in SHRs abdominal aorta. PMID- 22088250 TI - [The effects of atorvastatin on C-reactive protein induced Toll-like receptor 4 expression on CD14+ monocyte]. AB - OBJECTIVE: To investigate the effects of atorvastatin on C-reactive protein (CRP) induced Toll-Like receptor 4 (TLR4)expression on CD14+ monocyte, and the production of proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), matrix metalloproteinases-9 (MMP-9), and to study the anti inflammatory mechanisms of statins. METHODS: The monocytes were isolated from blood of healthy volunteers by the Ficoll density gradient and stimulated by CRP with different doses (5, 25, 50, 100 microg/ml) and different exposure time (6, 12, 24, 48 h). Cells were also incubated with atorvastatin of different doses (1.0, 2.5, 5.0, 7.5, 10.0 micromol/L) in the presence of CRP 50 microg/ml. The protein expression of TLR4 was measured by flow cytometry, mRNA expression of TLR4 and of myeloid differentiation protein (MD2)was detected by quantitative PCR. TNFalpha, IL-6, MMP-9 concentrations in supernatants of cultured medium were measured by ELISA. RESULTS: (1) Compared with the un-stimulated control group, enhanced TLR4 protein expression was already detected at a concentration of 5 microg/ml of CRP and increased in a dose-dependent manner (32.22 +/- 2.80)%, (49.94 +/- 5.58)%, (74.82 +/- 3.24)% and (90.82 +/-2.88)% at 5, 25, 50 and 100 microg/ml CRP. (2) TLR4 protein expression on 50 microg/ml CRP stimulated cells also increased in a time-dependent manner (29.80 +/- 2.70)%, (47.44 +/- 4.41)%, (81.71 +/- 2.92)% and (50.57 +/- 3.34)% after 6 h, 12 h, 24 h, 48 h. (3) When monocytes were incubated with CRP 50 microg/ml and atorvastatin (1.0, 2.5, 5.0, 7.5, 10.0 micromol/L), protein expression [(68.17 +/- 1.71)%, (52.43 +/- 1.38)%, (27.72 +/- 4.55)%, (17.46 +/- 3.20)%, (9.99 +/- 2.81)%] and mRNA expression (82.72%, 67.34%, 48.16%, 30.88%, 13.85%) of TLR4 as well as mRNA expression of MD2 (81.78%, 71.04%, 47.85%, 27.06%, 18.30%) were reduced in a dose-dependent manner. (4) Level of TNFalpha, IL-6 and MMP-9 in supernatants was significantly reduced by atorvastatin (2.5 micromol/L) compared with control group (P < 0.01). When monocyte incubated with CRP 50 microg/ml and atorvastatin 10.0 micromol/L, the level of TNFalpha, IL-6, MMP-9 decreased to (25.8 +/- 2.5) microg/ml, (128.2 +/- 14.7) pg/ml, (65.2 +/- 12.3) ng/ml, respectively. CONCLUSION: CRP increased the protein expression of TLR4 on CD14+ monocyte in a dose-dependent and time dependent manner. Atorvastatin can inhibit the signal transduction of TLR4 and reduce proinflammatory cytokines release induced by CRP on CD14 monocyte, and this might be one of the anti-inflammatory mechanisms of atorvastatin. PMID- 22088251 TI - [Prevalence and distributing feather of controllable cardiovascular risk factors in Chinese pilots]. AB - OBJECTIVE: To investigate the status of controllable risk factors of cardiovascular disease in Chinese pilots. METHODS: Pilots in seven regions of China were selected with cluster sampling. The rates of hypertension, diabetes mellitus,smoking and abnormal body mass index (BMI) as well as levels of total cholesterol, triglyceride and high density lipoprotein-cholesterol were obtained. RESULTS: (1) A total of 5012 pilots were selected and 4684 pilots whose data were effective were studied. (2) The prevalence rates of hypertension, high total cholesterol, triglyceride, low high density lipoprotein-cholesterol and diabetes mellitus were 8.07%, 7.47%, 14. 45%, 27.63% and 0.43%, respectively. The rate of smoking was 66.45%. The rat of increased BMI was 49.64%. (3) Significant difference existed on the rates of hypertension, total cholesterol, triglyceride, low high density lipoprotein-cholesterol, smoking and abnormal BMI among pilots from different regions (all P < 0.01). There was also a significant difference between the rates of hypertension, total cholesterol, triglyceride, smoking and abnormal BMI in different age groups (all P < 0.01). The rate of low high density lipoprotein-cholesterol was similar in different age groups (P > 0.05). (4) 88.96% of the participants had at least one controllable risk factor. 54.46% of the participants had at least two controllable risk factors. None of the participants had more than seven risk factors. There was a significant difference between the rates of pilots who have more than two controllable risk factors in different regions (P < 0.01). There was a significant difference between the rates of pilots who have more than two risk factors in different age groups (P < 0.01). CONCLUSIONS: There was high prevalence of controllable cardiovascular risk factors in Chinese pilots. Active intervention targeting these cardiovascular disease risk factors needs to be considered to reduce the risk of developing cardiovascular disease in Chinese pilots. PMID- 22088252 TI - [Impact of genetic polymorphisms on efficacy of antiplatelet therapy]. PMID- 22088253 TI - [Stromal interaction molecule 1 and cardiovascular diseases]. PMID- 22088254 TI - Tumoral and angiogenesis factors in hepatocellular carcinoma after locoregional therapy. AB - Locoregional therapy (LRT) is used as a bridge to orthotopic liver transplant (OLT) for hepatocellular carcinoma (HCC) patients. Liver explants in OLT patients with HCC were studied regarding both tumor stage, histology, and immunohistochemical staining for cytokeratin (CK)7, CK19, P53, Ki-67, and vascular endothelial growth factor (VEGF). Patients receiving no LRT (control) (n=30) were compared with LRT treatment groups with conventional transarterial chemoembolization (cTACE) (n=25) or drug-eluting bead transarterial chemoembolization (DEB TACE) (n=17). Tumor stage and histology were similar between treatment and control groups. The mean percent necrosis was significantly higher for treatment groups versus the control group (p<0.0001 for both groups versus control) and was significantly higher in the cTACE group versus the DEB TACE group. Only the DEB TACE group showed peritumoral CK19 positivity, and tumors were all CK19-negative. Using a threshold of 50% of tumoral cells, tumoral VEGF was significantly different between groups, with the control group having the highest degree of positivity; however, peritumoral VEGF was not significantly different between the groups. The Ki-67 proliferation fraction was higher in the treated groups with a statistically significant difference between the DEB treated group and those without treatment (p=0.02). There were no statistically significant differences in tumoral or peritumoral CK7 or p53. Percent necrosis and percent Ki-67 positivity were higher with LRT, with a significant difference between groups for percent necrosis, confirming that LRT causes necrosis and suggesting that treatment leads to increased proliferation and decreased tumoral VEGF. PMID- 22088255 TI - Cochlear implantation in a patient with superficial siderosis. AB - Superficial siderosis is a rare disease characterized by accumulation of hemosiderin in the leptomeninges, subpial tissue, spinal cord, and cranial nerves. The first clinicopathological description was reported in 1908. Most patients (95%) experience progressive bilateral hearing loss that begins early in the course of disease. The initial management of a patient with hearing loss secondary to superficial siderosis involves sound amplification using hearing aids. However, cochlear implants can be considered in cases where the patient can no longer gain significant benefit from hearing aids. Only 10 studies have described the use of cochlear implants in superficial siderosis and results have been variable. We report the case of a 65-year-old woman with bilateral progressive sensorineural hearing loss caused by superficial siderosis who benefited significantly from cochlear implantation. PMID- 22088256 TI - A scanning electron microscopic study of crimping of stapedial prostheses. AB - OBJECTIVE: The aim of this study was to evaluate, through the Scanning Electron Microscopy, the loop closure of four types of stapedial prostheses and to compare the different systems of crimping to the long process of the incus. MATERIALS AND METHODS: Four types of stapedial prostheses (one platinum-teflon, two different titanium and one nitinol-teflon pistons) were inserted in 40 specially prepared temporal bones simulating the in vivo stapedotomy procedure. Two pistons were crimped by single manual manoeuvre with a McGee microforceps; the remainders were self-retained and thermal-crimped, respectively. All the specimens were evaluated through the Operative Microscopy and the Scanning Electron Microscopy. RESULTS: Through the Operative Microscopy, all prostheses apparently achieved a correct adhesion to the long process of the incus; on the contrary the Scanning Electron Microscopy study demonstrated some limits of the manual crimping and the different coupling with the ossicular chain of each type of stapedial prosthesis. CONCLUSION: A complete adhesion of the prosthetic loop cannot be obtained because of the irregular profile of the incus at the site of attachment of the stapedial prosthesis. Consequently, on the basis of the morphological analysis with Scanning Electron Microscopy, in the surgical practice, the preference could be given to the stapedial prostheses that achieve greater contact such as the self retaining and thermal crimping pistons compared to the standard sized prostheses considered. PMID- 22088257 TI - Benign paroxysmal positional vertigo showing sequential translations of four types of nystagmus. AB - OBJECTIVE: We report a case of benign paroxysmal positional vertigo (BPPV) showing sequential translation of four types of nystagmus and discuss its pathophysiology. METHODS: The case was 65-year-old female. We analyzed her nystagmus three-dimensionally. RESULTS: At the first visit, she showed vertical torsio nystagmus of the posterior canal type of BPPV (P-BPPV) and subsequently showed recently reported geotropic nystagmus with a long time constant. Two weeks later, she showed apogeotropic nystagmus of the horizontal canal type of BPPV (AH BPPV) and subsequently a geotropic nystagmus with a short time constant of the horizontal canal type of BPPV (GH-BPPV). CONCLUSIONS: Three kind of nystagmus, namely P-BPPV, AH-BPPV and GH-BPPV can be explained by the otoconial debris hypothesis of the same ear. Finally, the recently reported geotropic nystagmus with a long time constant may be explained by a reversible lesion such as the denatured cupula or utricular imbalance of the same ear. PMID- 22088258 TI - Impact of residual ethmoid cells on postoperative course after endoscopic sinus surgery for chronic rhinosinusitis. AB - OBJECTIVE: Endoscopic sinus surgery (ESS) is a worldwide standard surgical procedure for chronic rhinosinusitis (CRS). Residual ethmoid cells (RECs), which result from failure to completely remove them, have been thought to be a cause of recurrence of CRS. Our objective was to investigate the relationship between the REC score and post ESS recurrence of CRS. METHODS: From January 2002 through December 2003, a total of 138 consecutive CRS patients (86 men and 52 women; mean age: 44 years) underwent ESS at the Department of Otorhinolaryngology, Ota General Hospital. CT was performed at 6 or more months post ESS for all patients. The left and right ethmoid sinuses were each divided into superior-anterior, inferior-anterior and posterior parts. The extent of RECs in each part was assessed using a 3-grade scoring system. The outcome of CRS was classified into a satisfactory outcome group and a poor outcome group based on the improvement rate determined from the pre ESS and post ESS CT image findings. The two groups were then compared for the age, gender, presence/absence of nasal polyps, presence/absence of allergic rhinitis, presence/absence of asthma, the peripheral eosinophil count (%) and the total REC score. In addition, the individual correlations between the above variables and the poor outcome group were analyzed by logistic regression analysis. RESULTS: The total REC score was 0 in only 35 (25.4%) of the total patients. The most common total REC scores were 1-6 in 85 (61.6%) patients. The superior-anterior part had the largest number of patients with an REC score of 1 or more. The satisfactory outcome group comprised 97 patients (70.3%), while the poor outcome group comprised 41 patients (29.7%). Comparison of these two groups found that the peripheral eosinophil count, the prevalence rate of asthma and the total REC score were each significantly higher in the poor outcome group than in the satisfactory outcome group. Logistic regression analysis identified a peripheral eosinophil count of >=9.5%, the presence of asthma and a total REC score of >=4 as factors that correlated significantly with a poor outcome. CONCLUSION: The findings of this study indicate that RECs are involved in the recurrence of CRS following ESS. It can be thought that how to achieve full opening of the superior-anterior part of the ethmoid sinus, which includes the frontal recess, will be an issue in the future. PMID- 22088259 TI - Ultrasensitive luminol electrochemiluminescence for protein detection based on in situ generated hydrogen peroxide as coreactant with glucose oxidase anchored AuNPs@MWCNTs labeling. AB - In this study, an ultrasensitive luminol electrochemiluminescence (ECL) immunosensor was constructed using carboxyl group functionalized multi-walled carbon nanotubes (MWCNTs) as platform and glucose oxidase (GOD) supported on Au nanoparticles (AuNPs) decorated MWCNTs (AuNPs@MWCNTs-GOD) as labels. Firstly, using poly(ethylenimine) (PEI) as linkage reagents, AuNPs@MWCNTs were prepared and introduced for binding of the secondary antibody (Ab(2)) and glucose oxidase (GOD) with high loading amount and good biological activity due to the improved surface area of AuNPs@MWCNTs and excellent biocompatibility of AuNPs. Then the GOD and Ab(2) labeled AuNPs@MWCNTs were linked to the electrode surface via sandwich immunoreactions. These localized GOD and AuNPs amplified luminol ECL signals dramatically, which was achieved by efficient catalysis of the GOD and AuNPs towards the oxidation of glucose to in situ generate improved amount of hydrogen peroxide (H(2)O(2)) as coreactant and the enhancement of AuNPs to the ECL reaction of luminol-H(2)O(2). The experimental results demonstrated that the proposed immunosensor exhibited sensitive and stable response for the detection of alpha-1-fetoprotein (AFP), ranging from 0.0001 to 80 ng mL(-1) with a limit of detection down to 0.03 pg mL(-1) (S/N=3). With excellent stability, sensitivity, selectivity and simplicity, the proposed luminol ECL immunosensor showed great potential in clinical applications. PMID- 22088261 TI - Ratiometric fluorescence imaging of dual bio-molecular events in single living cells using a new FRET pair mVenus/mKOkappa-based biosensor and a single fluorescent protein biosensor. AB - Genetically coded fluorescent protein (FP)-based biosensors are powerful tools for the non-invasive tracking of molecular events in living cells. Although a variety of FP biosensors are available, the simultaneous imaging of multiple biosensors (multi-parameter imaging) in single living cells remains a challenge and is far from routinely used to elucidate the intricate networks of molecular events. In this study, we established a novel combination of FP biosensors for dual-parameter ratiometric imaging, consisting of a new fluorescence resonance energy transfer (FRET) pair mVenus (yellow FP)/mKOkappa (orange FP)-based (abbreviated as YO) biosensor and a single FP-based biosensor Grx1-roGFP2. Under our imaging condition, 1.4+/-0.05% of Grx1-roGFP2 signal contributes to the mVenus channel and 5.2+/-0.12% of the mVenus signal contributes to the Grx1 roGFP2 channel. We demonstrate that such low degree of cross-talk causes negligible distortion of the ratiometric signal of the YO-based FRET biosensor and Grx1-roGFP2. By using this dual-parameter ratiometric imaging approach, we achieved simultaneous imaging of Src/Ca(2+) signaling and glutathione (GSH) redox potential in a single cell, which was previously unattainable. Furthermore, we provided direct evidence that epidermal growth factor (EGF)-induced Src signaling was negatively regulated by H(2)O(2) via its effect on GSH-based redox system, demonstrating the power of this dual-parameter imaging approach for elucidating new connections between different molecular events that occur in a single cell. More importantly, the dual-parameter imaging approach described in this study is highly extendable. PMID- 22088260 TI - 1,1'-Oxalyldiimidazole chemiluminescent enzyme immunoassay capable of simultaneously sensing multiple markers. AB - In order to rapidly and simultaneously quantify and screen trace levels of multiple biomarkers in a single sample, rapid 1,1'-oxalyldiimidazole chemiluminescence (ODI CL) was applied as a biosensor of immunoassays using various enzymes such as alkaline phosphatase (ALP) and horseradish peroxidise (HRP). (1) Fluorescein was formed from the reaction of fluorescein diphosphate (FDP) and immuno-complex conjugated with ALP. (2) Resorufin was formed from the reaction between Amplex Red and H(2)O(2) in the presence of immuno-complex conjugated with HRP. When ODI CL reagents (H(2)O(2) in isopropyl alcohol, ODI in ethyl acetate) were injected in a test tube or strip-well containing fluorescein and resorufin formed from above two reactions a bright CL emission spectrum having two peaks (518 nm for fluorescein and 602 nm for resorufin) was observed. The two peaks can be independently quantified with an appropriate statistical tool capable of deconvoluting multiple emission peaks. In conclusion, we expect that ODI chemiluminescent enzyme immunoassays (CLEIAs) using a couple of enzymes conjugated with antigen or antibody and substrates can rapidly and simultaneously quantify and screen multiple biomarkers in a single sample. PMID- 22088262 TI - Is there a twist in the Escherichia coli signal recognition particle pathway? AB - Integral membrane proteins (IMPs) are usually synthesized by membrane-bound ribosomes, and this process requires proper localization of ribosomes and IMP encoding transcripts. However, the underlying molecular mechanism of the pathway has not yet been fully established in vivo. The prevailing hypothesis is that ribosomes and transcripts are delivered to the membrane together during IMP translation by the signal recognition particle (SRP) and its receptor. Here, I discuss an alternative hypothesis that posits that ribosomes and transcripts are targeted separately. Ribosome targeting to the membrane might be mediated by the SRP receptor, rather than by SRP, and IMP-encoding transcripts might be targeted to the membrane in a translation-independent manner. According to this scenario, the SRP executes its essential function on the membrane at a later stage of the targeting pathway. PMID- 22088263 TI - High levels of brain-type creatine kinase activity in human platelets and leukocytes: a genetic anomaly with autosomal dominant inheritance. AB - The ectopic expression in peripheral blood cells of the brain-type creatine kinase (CKB) is an autosomal dominant inherited anomaly named CKBE (MIM ID 123270). Here, we characterized the CK activity in serum, platelets (PLT) and leukocytes (WBC) of 22 probands (from 8 unrelated families) and 10 controls. CK activity was measured by standard UV-photometry. Expression of the CKB gene was analyzed by real-time PCR and Western blotting. DNA sequencing including bisulfite treatment was used for molecular analysis of the CKB gene. Serum CK levels were comparable between probands and controls. CKBE probands revealed significantly higher CK activity in PLT (3.7 +/- 2.7 versus 179.2 +/- 83.0 U/10(12) PLT; p<0.001) and WBC (0.4 +/- 0.3 versus 2.6 +/- 2.1 U/10(9) WBC; p=0.004). Inhibitory anti-CKM antibodies did not affect CK activity indicating that the CK activity is generated exclusively by the CK-BB isoenzyme. CKB mRNA and protein levels were significantly higher in PLT and WBC from probands compared to controls. Re-sequencing of the entire CKB gene and methylation analysis of a CpG island revealed no alteration in CKBE probands. The genetic basis of CKBE remains unclear, however, we propose that a de-methylated CKB gene is inherited that leads to high CKB expression levels in myeloic precursor cells in the bone marrow. PMID- 22088264 TI - Comparing spatial accessibility to conventional medicine and complementary and alternative medicine in Ontario, Canada. AB - Health care investigations rarely consider conventional medicine (CM) and complementary and alternative medicine (CAM) simultaneously and spatial accessibility empirical research that incorporates both CM and CAM locations is novel. In this study, residents within municipalities of the Ontario province of Canada are compared in terms of spatial accessibility to a range of health care supplier 'destinations'. While areas with larger urban agglomerations generally exhibit superior levels of spatial accessibility to health care and diversity in medical service choice in comparison to more peripheral areas, considerable heterogeneity in accessibility occurs in both urban and rural settings. This study's identification of subtle spatial imbalances appends the literature by more precisely qualifying the typically reported 'urban-rich, rural-poor' assessment of health care service condition and also reinforces the need for policy-makers to appraise health care spatial accessibility differentials as a function of both CM and CAM endowment. PMID- 22088265 TI - From school to work: promoting the application of pre-qualification interprofessional education in the clinical workplace. AB - The rationale for Interprofessional Education (IPE) is based on the assumption it will improve practice. Despite evidence that it may modify attitudes and provide knowledge and skills for collaboration, there is little evidence about whether these skills can be transferred to practice. The aim of this research was to explore how midwifery students apply pre-qualification IPE learning to practice and to understand the factors in the clinical workplace that facilitate or hinder this application. A purposive sample of students, educators, Heads of Midwifery and new midwives from four universities throughout the United Kingdom participated in semi-structured interviews and focus groups. Emerging themes were developed using the principles of Grounded Theory. Participants articulated ways in which the clinical environment either promoted or prevented IPE in practice. The extent to which the clinical institution promoted IPE was made visible through the support for students during placements; the support for new midwives; and the evolution of professional roles. Buy-in for the IPE agenda in the workplace influences the ability of new midwives to apply IPE competencies to professional practice. The benefits of a theoretical foundation in interprofessional skills may be lost if students and new midwives find themselves working in contexts that do not make collaboration a priority. PMID- 22088266 TI - War stories: a qualitative analysis of narrative teaching strategies in the operating room. AB - BACKGROUND: "War stories" are commonplace in surgical education, yet little is known about their purpose, construct, or use in the education of trainees. METHODS: Ten complex operations were videotaped and audiotaped. Narrative stories were analyzed using grounded theory to identify emergent themes in both the types of stories being told and the teaching objectives they illustrated. RESULTS: Twenty-four stories were identified in 9 of the 10 cases (mean, 2.4/case). They were brief (mean, 58 seconds), illustrative of multiple teaching points (mean, 1.5/story), and appeared throughout the operations. Anchored in personal experience, these stories taught both clinical (eg, operative technique, decision making, error identification) and programmatic (eg, resource management, professionalism) topics. CONCLUSIONS: Narrative stories are used frequently and intuitively by physicians to emphasize a variety of intraoperative teaching points. They socialize trainees in the culture of surgery and may represent an underrecognized approach to teaching the core competencies. More understanding is needed to maximize their potential. PMID- 22088267 TI - SBAR M&M: a feasible, reliable, and valid tool to assess the quality of, surgical morbidity and mortality conference presentations. AB - BACKGROUND: The Surgical Morbidity and Mortality (M&M) conference is considered the golden hour of surgical education. However, evaluation methods for ensuring that quality M&M presentations efficiently contribute to resident education have not been clearly defined. To provide surgical trainees with the skills required to present a quality M&M presentation it is essential to have a robust tool to measure presentation skill and guide formative feedback. METHODS: A prospective observational study was conducted to develop an assessment tool for M&M conference. Literature review and expert consensus provided content for tool development. The tool, created using the situation, background, assessment, and recommendation format, was refined successively based on assessor feedback and assessed for reliability (internal consistency, interassessor reliability) and construct validity. RESULTS: Three successive iterations of the tool were developed. Internal consistency and interassessor reliability improved from the first to third versions. A trend also was shown for increasing construct validity with the third iteration of the tool. CONCLUSIONS: A psychometrically robust assessment tool based on the situation, background, assessment, and recommendation format was developed and validated to identify and improve the overall quality and educational value of the surgical M&M conference. PMID- 22088268 TI - Comparing three pedagogical approaches to psychomotor skills acquisition. AB - BACKGROUND: We compared traditional pedagogical approaches such as time- and repetition-based methods with proficiency-based training. METHODS: Laparoscopic novices were assigned randomly to 1 of 3 training conditions. In experiment 1, participants in the time condition practiced for 60 minutes, participants in the repetition condition performed 5 practice trials, and participants in the proficiency condition trained until reaching a predetermined proficiency goal. In experiment 2, practice time and number of trials were equated across conditions. RESULTS: In experiment 1, participants in the proficiency-based training conditions outperformed participants in the other 2 conditions (P < .014); however, these participants trained longer (P < .001) and performed more repetitions (P < .001). In experiment 2, despite training for similar amounts of time and number of repetitions, participants in the proficiency condition outperformed their counterparts (P < .038). In both experiments, the standard deviations for the proficiency condition were smaller than the other conditions. CONCLUSIONS: Proficiency-based training results in trainees who perform uniformly and at a higher level than traditional training methodologies. PMID- 22088269 TI - Seroprevalence and sero-conversion after vaccination against Peste des Petits Ruminants in sheep and goats from Awash Fentale District, Afar, Ethiopia. AB - A cross-sectional epidemiological study followed by vaccination and postvaccinal serum antibody assessment against Peste des Petits Ruminants (PPR) in small ruminant population of Awash Fentale District, Afar, Ethiopia, was conducted from September 2006 to June 2007 with the aim of investigating seroprevalence and post vaccination sero-conversion rate. A total of 1239 sera collected from sheep and goats which were not vaccinated, were screened by using nucleoprotein-based competitive enzyme-linked immunosorbent assay (c-ELISA). Only 21 (1.70%) animals were found to be positive. Following the base-line seroprevalence study, small ruminants in the area were vaccinated using the attenuated homologous PPR virus (Nigeria 75/1) strain vaccine, produced at National Veterinary Institute (NVI) in Debre-Zeit, Ethiopia. A total of 1096 small ruminants were resampled from the vaccinated population fourteen days after vaccination. The postvaccination sero conversion rate in the population was found to be 61.13%, indicating a relatively weak herd immunity. The main reason for the low sero-conversion could be the thermolabile nature of the vaccine, since no statistically significant difference was observed between small ruminants vaccinated by Veterinary Professionals and Community Animal Health Workers (CAHWs), using Chi-squared test at 95% CI (P>0.05). This signifies the need for thermostable vaccine that could potentially increase the herd immunity in addition to that being administered by CAHWs independently. The current finding indicated that CAHWs could participate in vaccination campaigns in such areas as Afar, where there are few veterinarians despite of the huge livestock populations, as means of pastoralists' livelihood. PMID- 22088270 TI - Quantitative detection of Cryptosporidium oocyst in water source based on 18S rRNA by alternately binding probe competitive reverse transcription polymerase chain reaction (ABC-RT-PCR). AB - We describe an assay for simple and cost-effective quantification of Cryptosporidium oocysts in water samples using a recently developed quantification method named alternately binding probe competitive PCR (ABC-PCR). The assay is based on the detection of 18S rRNA specific for Cryptosporidium oocysts. The standard curve of the ABC-PCR assay had a good fitting to a rectangular hyperbola with a correlation coefficient (R) of 0.9997. Concentrations of Cryptosporidium oocysts in real river water samples were successfully quantified by the ABC-reverse transcription (RT)-PCR assay. The quantified values by the ABC-RT-PCR assay very closely resemble those by the real time RT-PCR assay. In addition, the quantified concentration in most water samples by the ABC-RT-PCR assay was comparable to that by conventional microscopic observation. Thus, Cryptosporidium oocysts in water samples can be accurately and specifically determined by the ABC-RT-PCR assay. As the only equipment that is needed for this end-point fluorescence assay is a simple fluorometer and a relatively inexpensive thermal cycler, this method can markedly reduce time and cost to quantify Cryptosporidium oocysts and other health-related water microorganisms. PMID- 22088271 TI - Survival dynamics of fecal bacteria in ponds in agricultural watersheds of the Piedmont and Coastal Plain of Georgia. AB - Animal agriculture in watersheds produces manure bacteria that may contaminate surface waters and put public health at risk. We measured fecal indicator bacteria (commensal Escherichia coli and fecal enterococci) and manure pathogens (Salmonella and E. coli 0157:H7), and physical-chemical parameters in pond inflow, within pond, pond outflow, and pond sediments in three ponds in agricultural watersheds. Bishop Pond with perennial inflow and outflow is located in the Piedmont, and Ponds A and C with ephemeral inflow and outflow in the Coastal Plain of Georgia. Bromide and chloride tracer experiments at Bishop Pond reflected a residence time much greater than that estimated by two models, and indicated that complete mixing within Bishop Pond was never obtained. The long residence time meant that fecal bacteria were exposed to solar UV-radiation and microbial predation. At Bishop Pond outflow concentrations of fecal indicator bacteria were significantly less than inflow concentrations; such was not observed at Ponds A and C. Both Salmonella and E. coli 0157:H7 were measured when concomitant concentrations of commensal E. coli were below the criterion for surface water impairment indicating problems with the effectiveness of indicator organisms. Bishop Pond improved down stream water quality; whereas, Ponds A and C with ephemeral inflow and outflow and possibly greater nutrient concentrations within the two ponds appeared to be less effective in improving down stream water quality. PMID- 22088272 TI - What are the costs and benefits of biodiversity recovery in a highly polluted estuary? AB - Biodiversity recovery measures have often been ignored when dealing with the restoration of degraded aquatic systems. Furthermore, biological valuation methods have been applied only spatially in previous studies, and not jointly on a temporal and spatial scale. The intense monitoring efforts carried out in a highly polluted estuary, in northern Spain (Nervion estuary), allowed for the economic valuation of the costs and the biological valuation of the benefits associated with a 21 years sewage scheme application. The analysis show that the total amount of money invested into the sewage scheme has contributed to the estuary's improvement of both environmental and biological features, as well as to an increase in the uses and services provided by the estuary. However, the inner and outer parts of the estuary showed different responses. An understanding of the costs and trajectories of the environmental recovery of degraded aquatic systems is increasingly necessary to allow policy makers and regulators to formulate robust, cost-efficient and feasible management decisions. PMID- 22088273 TI - Single-stage subchordal resection and reconstruction of idiopathic laryngotracheal stenosis in a male patient. PMID- 22088274 TI - Visualization of flow structures in Fontan patients using 3-dimensional phase contrast magnetic resonance imaging. AB - OBJECTIVE: Our objective was to analyze 3-dimensional (3D) blood flow patterns within the total cavopulmonary connection (TCPC) using in vivo phase contrast magnetic resonance imaging (PC MRI). METHODS: Sixteen single-ventricle patients were prospectively recruited at 2 leading pediatric institutions for PC MRI evaluation of their Fontan pathway. Patients were divided into 2 groups. Group 1 comprised 8 patients with an extracardiac (EC) TCPC, and group 2 comprised 8 patients with a lateral tunnel (LT) TCPC. A coronal stack of 5 to 10 contiguous PC MRI slices with 3D velocity encoding (5-9 ms resolution) was acquired and a volumetric flow field was reconstructed. RESULTS: Analysis revealed large vortices in LT TCPCs and helical flow structures in EC TCPCs. On average, there was no difference between LT and EC TCPCs in the proportion of inferior vena cava flow going to the left pulmonary artery (43% +/- 7% vs 46% +/- 5%; P = .34). However, for EC TCPCs, the presence of a caval offset was a primary determinant of inferior vena caval flow distribution to the pulmonary arteries with a significant bias to the offset side. CONCLUSIONS: 3D flow structures within LT and EC TCPCs were reconstructed and analyzed for the first time using PC MRI. TCPC flow patterns were shown to be different, not only on the basis of LT or EC considerations, but with significant influence from the superior vena cava connection as well. This work adds to the ongoing body of research demonstrating the impact of TCPC geometry on the overall hemodynamic profile. PMID- 22088275 TI - Responses of antioxidant gene, protein and enzymes to salinity stress in two genotypes of perennial ryegrass (Lolium perenne) differing in salt tolerance. AB - Salinity could damage cellular membranes through overproduction of reactive oxygen species (ROS), while antioxidant capacities play a vital role in protecting plants from salinity caused oxidative damages. The objective of this study was to investigate the toxic effect of salt on the antioxidant enzyme activities, isoforms and gene expressions in perennial ryegrass (Lolium perenne L.). Salt-tolerant 'Quickstart II' and salt-sensitive 'DP1' were subjected to 0 and 250 mM NaCl for 12 d. Salt stress increased the content of lipid peroxidation (MDA), electrolyte leakage (EL) and hydrogen peroxide (H2O2), to a greater extent in salt-sensitive genotype. Salt-stressed plant leaves exhibited a greater activity of superoxide dismutase (SOD, EC 1.15.1.1), peroxidase (POD, EC 1.11.1.7), ascorbate peroxidase (APX, EC 1.11.1.11) at 4d after treatment (DAT), but a lower level of enzyme activity at 8 and 12d, when compared to the control. Catalase (CAT, EC 1.11.1.6) activity was greater at 4 DAT and thereafter decreased in salt tolerant genotype relative to the control, whereas lower than the control during whole experiment period for salt-sensitive genotype. There were different patterns of five isoforms of SOD, POD and two isoforms of APX between two genotypes. Antioxidant gene expression was positively related to isoenzymatic and total enzymatic activities during 12-d salt-treated leaves of two genotypes, with a relatively higher level in salt-tolerant genotype. Thus, salt tolerance could be related to the constitutive/induced antioxidant gene, leading to more efficient enzyme stimulation and protection in perennial ryegrass. PMID- 22088276 TI - Amelioration of atherosclerosis by tanshinone IIA in hyperlipidemic rabbits through attenuation of oxidative stress. AB - Oxidative stress plays a crucial role in atherogenesis, which raises the possibility of using antioxidants to ameliorate atherosclerosis. In the present study, we aim to determine the effects of tanshinone IIA (TSIIA) on atherosclerosis in hyperlipidemic rabbits. After feeding the rabbits on a high lipid diet for 90 days, they developed severe atherosclerotic lesions both morphologically and biochemically and exhibited significantly elevated serum lipid, malondialdehyde (MDA) and oxidized low density lipoprotein (oxLDL) levels. Oral administration of TSIIA (3-30 mg/kg) greatly inhibited the formation of atherosclerotic lesions. In TSIIA-treated rabbits, there was a marked reduction in serum and aortic lipid peroxide product content, represented by MDA and oxLDL, whereas enhanced activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were observed. However, TSIIA had no effect on serum lipid profiles. These results suggest that TSIIA attenuates oxidative stress by decreasing oxLDL production and enhancing activities of SOD and GPx, which might be contributed to the amelioration of atherosclerosis. PMID- 22088277 TI - Anti-proliferative activity and chemoprotective effects towards DNA oxidative damage of fresh and cooked Brassicaceae. AB - Epidemiological evidence shows that regular consumption of Brassicaceae is associated with a reduced risk of cancer and heart disease. Cruciferous species are usually processed before eating and the real impact of cooking practices on their bioactive properties is not fully understood. We have evaluated the effect of common cooking practices (boiling, microwaving, and steaming) on the biological activities of broccoli, cauliflower and Brussels sprouts. Anti proliferative and chemoprotective effects towards DNA oxidative damage of fresh and cooked vegetable extracts were evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3 carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and Comet assays on HT-29 human colon carcinoma cells. The fresh vegetable extracts showed the highest anti proliferative and antioxidant activities on HT-29 cells (broccoli>cauliflower = Brussels sprouts). No genotoxic activity was detected in any of the samples tested. The cooking methods that were applied influenced the anti-proliferative activity of Brassica extracts but did not alter considerably the antioxidant activity presented by the raw vegetables. Raw, microwaved, boiled (except broccoli) and steamed vegetable extracts, at different concentrations, presented a protective antioxidative action comparable with vitamin C (1 mm). These data provide new insight into the influence of domestic treatment on the quality of food, which could support the recent epidemiological studies suggesting that consumption of cruciferous vegetables, mainly cooked, may be related to a reduced risk of developing cancer. PMID- 22088278 TI - [Auditory neuropathy spectrum disorder in children]. PMID- 22088279 TI - [CT and MRI diagnosis of congenital stenosis of the internal auditory canal]. AB - OBJECTIVE: To investigate multiple slice computed tomography (MSCT) and magnetic resonance imaging (MRI) features of congenital stenosis of the internal auditory canal (CSIAC) and improve the ability for diagnosis. METHOD: Thirteen cases with fifteen ears were studied. In all cases a MSCT and MRI was performed. RESULTS: Eleven cases were unilateral, and 2 cases were bilateral. MSCT could show the narrowness of IAC. Three cases were isolated, but the others were combined with inner ear malformations. One ear had inner, middle and outer ear malformations. One ear had inner, middle, and outer ear malformations with a frontal bone malformation. MRI demonstrated that all of the vestibulocochlear nerves were hypoplastic. The cochlear nerve in seven ears was not present, in seven ears the nerve was thinner, and in the last case it was poorly visualized. The facial nerve in two ears was hypoplastic. Volume rendering (VR) could present the degree of the narrowed internal auditory canals, combined with other inner ear anomalies. CONCLUSION: MSCT will show the degree of the narrow internal auditory canals and combined anomalies, while the MRI can further demonstrate the nerves' development. PMID- 22088280 TI - [Analysis of the effectiveness in patients who were treated with a course of drugs for sudden deafness which was present for at least three weeks]. AB - OBJECTIVE: To investigate and analyze the significance of a course of glucocorticosteroids and other drugs for the treatment of patients with sudden deafness present for at least three weeks. METHODS: A retrospective review was done on 48 patients (58 ears) with sudden deafness present for at least three weeks or more, who were admitted to the Department of Otorhinolaryngology, Peking University People's Hospital from November 2002 to July 2010. The patients were divided into three groups by the type of hearing threshold. The different treatments were used in the three groups. The SPSS 17.0 software was used to analyze the data. RESULTS: In patients with a low tone hearing loss (6 ears), 83.3% improved. For patients with a high tone loss (22 ears) 31.8% improved. For a flat tone hearing loss (30 ears) 36.7% improved. For patients with a hearing loss more than one year (12 ears) there was improvement in 58.3% (7 ears) of the patients. In 9 ears which had a flat tone hearing loss of 90 dB or greater before treatment, 77.8% (7 ears) improved with 33.3% (3 ears) having a significant improvement. In 21 ears which had a hearing threshold was under 90 dB, 14.3% (3 ears) improved. CONCLUSIONS: In the treatment of patients with sudden deafness which was longer than 21 days the treatment was significant, especially for those who had a 90 dB or greater flat-tone type hearing threshold before treatment. Even though the hearing loss was more than a year in some patients there was still a benefit from treatment. PMID- 22088281 TI - [Tonal audiometry of GJB2 235delC single heterozygous mutation carriers]. AB - OBJECTIVE: To analyze GJB2 235delC monoallelic mutation carrier individuals and test the possible presence and incidence of audiometric abnormalities among 30-60 years old carriers of the 235delC mutations. METHODS: A total of 32 unrelated subjects with nonsyndromic hearing loss were screened for the 235delC mutation. Tonal audiometric analysis was performed on the 235delC mutation carrier group and on a non-carrier control group. RESULTS: Audiometric evaluations in the control group showed the presence of thresholds within normal limits at all frequencies, while carriers of the 235delC mutation presented with decreased hearing at 1000 Hz and 2000 Hz (age 40-49 years and 50-59 years), and 4000 and 8000 Hz (age 30-59 years), P < 0.05. The hearing loss of carriers gradually increased with age. CONCLUSIONS: GJB2 235delC heterozygous carriers may be a risk group for high-frequency hearing loss. Hearing thresholds may deteriorate in the intermediate frequencies over the age of 40. PMID- 22088282 TI - [Observation of bacterial biofilms in patients with chronic rhinosinusitis]. AB - OBJECTIVE: To explore the presence of bacterial biofilms (BF) in patients with CRS and the effect of BF on clinical symptoms and postoperative outcomes. METHODS: Seventy-two patients with chronic sinusitis were enrolled in this study. The control group included 15 patients with deviation of the nasal septum and 10 patients had a fracture of the nasal bone. Mucosa of the uncinate process or ethmoid near the ostium of the maxillary sinus was obtained during endoscopic sinus surgery. The specimens were subjected to scanning electron microscopy. Patients were followed for 1 year and observed by the Lund-Kennedy endoscopy, and the Haikou standard classification (ESS-1997). Statistical analysis was performed by t-test or chi-square test. RESULTS: Three patients were lost to follow-up. The scanning electron microscopy analysis showed bacterial biofilms in 49 of the 69 patients with chronic sinusitis. A marked destruction of the epithelium and cilia was observed in samples positive for bacterial biofilms. No bacterial biofilms were detected in the control group, and scanning electron microscopy showed normal epithelium and cilia in those specimens. There was no significant difference in gender, classification or duration of disease between the BF(-) and BF(+) groups. At six months and one year postoperative, the Lund-Kennedy endoscopy scores for CRS patients with BF (4.78 +/- 1.67; 4.55 +/- 1.61) were significantly higher than those without BF (3.65 +/- 1.39; 3.65 +/- 1.18) (t = 2.654, P < 0.01; t = -2.264, P < 0.05). Based on the Haikou standard classification, there was a significantly difference between patients with BF and those without BF (chi2 = 18.014, 22.063, P < 0.001, respectively). CONCLUSIONS: Different life stages of bacterial biofilms were demonstrated to be present in CRS. Gender, classification or duration of disease did not affect the presence of bacterial biofilms in patients with CRS. There is a correlation between bacterial biofilms and an unfavorable outcome in patients with CRS after ESS. PMID- 22088283 TI - [A preliminary study of radionuclide imaging of the nasal lymphatic system in nasal polyps]. AB - OBJECTIVE: To explore the role of nasal mucosal lymphatic drainage in the pathogenesis of nasal polyps. METHODS: There were 25 cases in the experimental group who had nasal polyps (which was further divided into Malm-1, Malm-2, Malm-3 level 3 subgroups) and 6 cases in the control group, including thyroid cancer and laryngeal cancer patients who had normal nasal structure. The nasal polyps in the experimental group and the middle turbinate in the control group were injected with a radionuclide and a radionuclide imaging technique was used to image the nasal mucosal lymphatics. The lymphatic drainage status of the nasal mucosa through the imaging results was analysed. RESULTS: The T/NT ratio (radioactivity counting) of the region of interest (ROI) was 20. 66 +/- 1.89 in the control group and 29. 33 +/- 6.34 in the experimental group. The difference was significant (t = 3.275, P < 0.05). The T/NT ratio of the ROI was 24.40 +/- 3.19 in the Malm-1 level group, 29.31 +/- 3.39 in the Malm-2 level group, 39.21 +/- 3.15 in the Malm-3 level group. The differences of qualitative analysis were significant (F = 38. 980, P < 0.05). The quantitative analysis showed that at the injection site, signs of lymphatic development and drainage were not found in the control group or experimental group, but the phenomenon of contrast media retention existed at the injection site in the experimental group. CONCLUSION: Lymphatic drainage dysfunction exists in patients with nasal polyps, and it may play a role in the pathogenesis of nasal polyps. PMID- 22088284 TI - [Effect of hyoid suspension with uvulopalatopharyngoplasty in the treatment of obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To discuss the methodology and therapeutic effect of hyoid suspension in association with uvulopalatopharyngoplasty (UPPP) in the treatment of severe obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: Sixty-nine patients with severe OSAHS (apnea hyponea index, AHI > 30) were treated with hyoid suspension and UPPP. Sixty-one patients were followed for 6 months (48 of them for 12 months). Polysomnogram (PSG) tests were performed and an Epworth sleepiness scale (ESS) was recorded preoperatively and postoperatively in these patients. RESULTS: After the surgery,the snoring of the patients disappeared or was alleviated to varing degrees. Eighteen patients underwent fiberoptic nasopharyngolaryngoscopic examination. Twelve of them showed palatopharyngeal and glossopharyngeal stenosis was improved 6 months after surgery. Six patients showed no change, but had no glossoptosis. Fourteen patients underwent fiberoptic nasopharyngolaryngoscopic examination 1 year after surgery, with no recurrence of the stenosis being found. A decrease of 50% in the AHI was considered effective, and in patients the effective rate was 78.7% (48/61) 6 months after the operation and 75.0% (36/48) 1 year after the operation. The average AHI decreased from 44.8 to 15.1 and 17.2, and the minimum arterial oxygen saturation average increased from 0.512 to 0.880 and 0.730. Matching t tests were utilized and the results of follow-up indicated that there was a significant improvement in the indexes in those cases which could be followed up (P < 0.01). The average of the ESS was 6.7 six months after operation and 7.2 one year after operation, with a significant decrease compared to the preoperative (16.6) data (P < 0.01). CONCLUSIONS: Modified hyoid suspension in association with UPPP has the advantage of a simple operation, short hospitalization and less expense, and the effect of the operation was significant. Patients with palatopharyngeal and glossopharyngeal stenosis should be chosen for this operation. PMID- 22088285 TI - [A comparison between endoscopic-assisted submandibular gland resection via retroauricular hairline incision and conventional submandibular gland resection]. AB - OBJECTIVE: To assess the feasibility, the risks and the advantages of endoscope assisted submandibular gland resection using a retroauricular hairline incision (RAHI) by comparing it with the conventional submandibular gland resection. METHODS: Twenty eight patients with benign lesions of the submandibular gland were included in the prospective clinically controlled study. Thirteen patients had endoscope-assisted resection using the RAHI approach and 15 cases had conventional transcervical approach resection. The size, location and adjacency of all lesions were evaluated by CT or MRI before surgery. The pathologic diagnoses of all cases were identified as benign diseases using fine needle aspiration biopsy. The two groups were compared for incision length, operation time, bleeding, incision cosmetic result, and complications. RESULTS: All 28 operations were successfully performed. Incision length in the endoscopic group was significantly longer than that in the transcervical group (Z = -4.516, P < 0.01), and the surgical time was longer in the endoscopic group (Z = -3.263, P < 0.01). After three months the mean subjective satisfaction score for the incision scar in the endoscopic group was significantly higher than that in the transcervical group (Z = -4.472, P < 0.01). In the endoscopic group, 2 cases (15.4%) with temporary numbness of the earlobe and 1 case (7.7%) with a temporary marginal mandibular nerve paralysis were found postoperatively. However, they recovered within 1 month. All 28 patients were disease free with a follow-up of 10 to 24 months (median of 18 months). CONCLUSIONS: Endoscope-assisted submandibular gland resection via RAHI is feasible and safe for the treatment of benign submandibular gland lesions. In comparison with the transcervical approach, this method can provide better cosmetic results without significant complications. PMID- 22088286 TI - [Inhibitory effects of small interfering RNA targeting c-myc in combination with 5-fluorouracil on the growth in vitro and in vivo]. AB - OBJECTIVE: To observe the effects of small interfere RNA (siRNA) targeting the c myc in combination with 5-fluorouracil (5-Fu) on the growth of Hep-2 cells in vitro and in vivo. METHODS: Hep-2 cells transfected with or without c-myc siRNA were treated with 5-Fu for 48 h. C-myc protein levels in Hep-2 cells were detected using the Western blot. The cell cycle was analyzed by flow cytometry. Hep-2 cells were subcutaneously inoculated into the back of BALB/c nude mice to establish the implanted laryngeal squamous carcinoma model. PBS, c-myc siRNA, and 5-Fu, alone or in combinations were administered i.p. The mice were sacrificed after the treatments and the tumor masses were removed to determine the tumor volume and weight. The inhibitory rate was calculated. Expression of c-myc in tumor tissue was detected by immunocytochemistry and cell apoptosis was analyzed by terminal transferase dUTP nick end labeling (TUNEL). RESULTS: The protein levels of c-myc decreased after transfected with c-myc siRNA. C-myc siRNA transfected cells showed an increase in the percentage of cells in the GO-G1 phase and a decrease in the percentage of cells in the S phase. When combined with 5-Fu, the results were improved. The tumor growth was faster in the control group and was significantly slower in the c-myc siRNA plus 5-Fu group than that in the c-myc siRNA group or 5-Fu group (P < 0.05). The tumor weight in the c-myc siRNA plus 5-Fu group was significantly smaller than that in the c-myc siRNA or 5 Fu group (P < 0.05). Immunohistochemistry showed that c-myc siRNA inhibited the expression of c-myc in tumor tissues in the c-myc siRNA group and c-myc siRNA plus 5-Fu group (P < 0.05). The number of apoptotic cells in the c-myc siRNA plus 5-Fu group was higher than those in the c-myc siRNA groups (P < 0.05). CONCLUSIONS: C-myc siRNA inhibits the expression of c-myc in Hep-2 cells and in the tumor tissues of nude mice. C-myc siRNA combined with 5-Fu inhibits the growth of implanted laryngeal squamous carcinoma and promotes cell apoptosis. C myc could become a novel target for the treatment of laryngeal squamous carcinoma. PMID- 22088287 TI - [Effects of celecoxib combined with radiotherapy on apoptosis of CNE-2Z cell lines]. AB - OBJECTIVE: To investigate the effects of celecoxib combined with radiotherapy on apoptosis of CNE-2Z cell lines and the potential mechanisms. METHODS: Four groups were used, a control, celecoxib (25 micromol/L celecoxib), irradiation (8 Gy X ray) and celecoxib plus irradiation. The radiosensitising effect was detected by clone formation experiment. Flow cytometry was used to detect the apoptosis rate of cells. The expressions of Bcl-2 and Bax were assessed by immunocytochemistry. Western blot was used to examine the expression of Caspase-3. RESULTS: Celecoxib enhanced the radiosensitivity of CNE-2Z cells. In experimental group, the mean surviving fraction and the mean lethal dose of CNE-2Z cells were 0.50 and 2.36 respectively. Compared with the irradiated group, there was significant differences between the two groups (P < 0.01). Celecoxib combined with radiotherapy up-regulation the expression of Bax. The score of the expression of Bax in the control group and the experimental group were 1.221 +/- 0.116 and 2.758 +/- 0.256 respectively. Celecoxib combined with radiotherapy could inhibit the expression of the protein of Bcl-2. The score of the expression of Bcl-2 in the control group and the experimental group were 2.559 +/- 0.144 and 1.253 +/- 0.114 respectively, with significant differences (P < 0.01). Celecoxib combined with radiotherapy could increase the apoptosis rate of tumor cells with significant differences (F = 7.63, P < 0.01). Western blot showed that the expression of Caspase-3 was strengthened. CONCLUSION: Celecoxib combined with radiotherapy could induce apoptosis and enhance the radiosensitivity of human nasopharyngeal carcinoma CNE-2Z cell lines. PMID- 22088288 TI - [Vibrant soundbridge implantation (two cases report)]. AB - OBJECTIVE: To investigate the effect of Vibrant Soundbridge (VSB) implantation. METHODS: In accordance with the indications for VSB implantation, surgeries were done for two patients who suffered from either a sensorineural or conductive hearing loss (microtia). Their preoperative auditory thresholds (0.5, 1, 2 and 4 kHz) were 56 dB HL and 61 dB HL. The VSB was turned on and adjusted seven weeks after surgery. RESULTS: Postoperative auditory thresholds of the two patients were improved. Their pure tone thresholds were 32 dB HL and 40 dB HL, and the respective improvement was 24 dB HL and 21 dB HL. There was no facial paralysis, vertigo and tinnitus. CONCLUSION: Patients with a sensorineural or conductive hearing loss may benefit from VSB implantation. PMID- 22088290 TI - [Analysis on effect of endoscopic nasal cavity surgery expansion in 108 cases]. AB - OBJECTIVE: To investigate the efficacy of endoscopic nasal cavity enlarging surgery for the alleviation of nasal obstruction. METHODS: One hundred and eight patients with deviation of the nasal septum (DNS) and chronic hypertrophic rhinitis (CHR) were included in this study. Individualized operations were performed. DNS patients were treated by three line tension relaxing correction or nasal septum plasty. CHR patients were treated by inferior turbinate out fracture in combination with plasma radiofrequency ablation for reducing the volume of nasal soft tissue, sub-mucoperiosteal partial resection of the inferior turbinate or partial inferior turbinectomy. RESULTS: All patients were followed for 3-12 months after surgery with an effective improvement in 97.2%. Symptoms of headache or complications of rhinitis sicca were not found. CONCLUSIONS: Being careful to keep the physiological function of nasal mucosa, the integrity of the nasal septum, appropriate expansion of the nasal cavity volume, and restore ventilation with bilateral symmetry of the nasal cavity, satisfactory relief of nasal obstruction can be achieved. PMID- 22088289 TI - [Meta-analysis of surgical techniques for preventing Frey syndrome and a concave facial deformity after parotidectomy]. AB - OBJECTIVE: To explore the curative effects on surgical methods for the prevention of Frey syndrome and a concave facial deformity after parotidectomy. METHODS: A literature search was performed using the Wianfang Database, Chinese Biomedical Literature Disk Database, Chinese Digital Hospital Library and Chinese Scientific Journals Database of VIP from January 1989 to December 2008. Twenty-six Chinese language controlled studies involving surgical techniques for prevention of Frey syndrome and the concave facial deformity after parotidectomy were identified. Review manager 4.2 software was applied for Meta analysis. RESULTS: Meta-analysis for surgical techniques to prevent symptomatic Frey syndrome, a positive starch iodine test, and contour deformity, favored intervention with a cumulative odds ratio (OR) of 0.14 [95% confidence interval (CI), 0.07-0.25]; OR, 0.21 (95% CI, 0.17-0.26); and OR, 0.09 (95% CI, 0.04-0.19), respectively. There was a significant difference in the incidence of these complications between surgical treatment groups and control groups (Z = 6.42, Z = 13.70, Z = 6.43, all P < 0.05). The application of a sternocleidomastoid muscle flap decreased the incidence of symptomatic Frey syndrome (Z = 2.33, P < 0.05), positive starch iodine test (Z = 7.48, P < 0.05) and contour deformity (Z = 7.78, P < 0.05). The application of acellular dermal matrix decreased the incidence of symptomatic Frey syndrome (Z = 6.02, P < 0.05) and positive starch-iodine test (Z = 5.72, P < 0.05) but did not decrease the incidence of contour deformity (Z = 1.27, P > 0.05). CONCLUSIONS: Meta-analysis of operative techniques to prevent symptomatic Frey syndrome, a positive starch-iodine test, and facial asymmetry suggests that such methods are likely to reduce the incidence of these complications and improve the quality of life after parotidectomy. PMID- 22088291 TI - [Nasal polyps in ethmoid and sphenoid sinus with oculomotor nerve paralysis: a case report]. PMID- 22088292 TI - [Report of a case with hemophilia B complicated with traumatic nosebleed as the first symptom]. PMID- 22088293 TI - [Analysis and treatment of 13 histiocytic necrotizing lymphadenitis cases]. PMID- 22088294 TI - [Remote monitoring of home-based noninvasive ventilation in children with obstructive sleep apnea-hypopnea syndrome and concomitant risk factors]. PMID- 22088295 TI - [Benign juvenile melanoma of auricle: a case report]. PMID- 22088296 TI - [One case of inflammatory myofibroblastic tumor of the temporal bone]. PMID- 22088297 TI - [Laryngeal manifestation of acquired immunodeficiency syndrome in a case]. PMID- 22088298 TI - [Syphilis of larynx--chancre epiglottis]. PMID- 22088299 TI - [Advances in diagnosis and surgical treatment of congenital malformation of the external and middle ear]. PMID- 22088300 TI - [Evaluation of therapeutic efficacy of olfactory disorders with glucocorticoid]. PMID- 22088301 TI - [Palliation of head and neck cancer]. PMID- 22088302 TI - [An introduction to the international pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma]. PMID- 22088303 TI - Hyperthermia modifies muscle metaboreceptor and baroreceptor modulation of heat loss in humans. AB - The relative influence of muscle metabo- and baroreflex activity on heat loss responses during post-isometric handgrip (IHG) exercise ischemia remains unknown, particularly under heat stress. Therefore, we examined the separate and integrated influences of metabo- and baroreceptor-mediated reflex activity on sweat rate and cutaneous vascular conductance (CVC) under increasing levels of hyperthermia. Twelve men performed 1 min of IHG exercise at 60% of maximal voluntary contraction followed by 2 min of ischemia with simultaneous application of lower body positive pressure (LBPP, +40 mmHg), lower body negative pressure (LBNP, -20 mmHg), or no pressure (control) under no heat stress. On separate days, trials were repeated under heat stress conditions of 0.6 degrees C (moderate heat stress) and 1.4 degrees C (high heat stress) increase in esophageal temperature. For all conditions, mean arterial pressure was greater with LBPP and lower with LBNP than control during ischemia (all P <= 0.05). No differences in sweat rate were observed between pressure conditions, regardless of the level of hyperthermia (P > 0.05). Under moderate heat stress, no differences in CVC were observed between pressure conditions. However, under high heat stress, LBNP significantly reduced CVC by 21 +/- 4% (P <= 0.05) and LBPP significantly elevated CVC by 14 +/- 5% (P <= 0.05) relative to control. These results show that sweating during post-IHG exercise ischemia is activated by metaboreflex stimulation, and not by baroreflexes. In contrast, our results suggest that baroreflexes can influence the metaboreflex modulation of CVC, but only at greater levels of hyperthermia. PMID- 22088305 TI - Study of the influence of psychological factors in the etiology of vocal nodules in women. AB - OBJECTIVE: The role placed by certain psychological factors such as stress and personality on the development of vocal nodules has not yet been established. The aim of this case-control type study is to analyze the relationship between these psychological factors and the presence of vocal nodules while also considering the professional and social aspects of the subjects suffering from this pathology. METHODS: The case group is made up of 50 patients diagnosed with vocal nodules and with at least 6 months of evolution. The control group is made up of 50 patients diagnosed with nasal respiratory insufficiency. All the patients were examined by laryngeal stroboscopy. For the personality study, the perceived stress, and the voice use, the Minnesota Multiphasic Personality Inventory-2, Levenstein Perceived Stress Questionnaire, and Goldman Voice Use Survey were used, respectively. RESULTS: The subjects with vocal nodules presented a mean perceived stress score of 0.41+/-0.09, which was higher than that of the control group (0.35+/-0.06), the differences observed being statistically significant (P<0.001). In the personality study (MMPI-2), the only scale that was associated with the presence of the vocal nodules was that of psychomotor acceleration. The mean score obtained for the scale was 51.64+/-8.25 in the vocal nodule group and 45.02+/-0.06 in the control group (P<0.001). In the analysis of voice use, the subjects with vocal nodules scored 9.31+/-1.36, which was significantly higher than the score of the control group (8.07+/-1.24; P<0.001). In addition, other variables were associated with the presence of vocal nodules, such as being young and working in professions considered to be of vocal risk. CONCLUSIONS: Perceived stress and personality features of hyperactivity and impulsivity are independent factors related to vocal nodules. PMID- 22088304 TI - Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias. AB - Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ~4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential. PMID- 22088306 TI - Design, synthesis and in vitro evaluation of novel chroman-4-one, chroman, and 2H chromene derivatives as human rhinovirus capsid-binding inhibitors. AB - As part of an effort to generate broad-spectrum inhibitors of rhinovirus replication, novel series of (E)-3-[(E)-3-phenylallylidene]chroman-4-ones 1a-e, (E)-3-(3-phenylprop-2-yn-1-ylidene)chroman-4-ones 2a and 2b, (Z)-3-[(E)-3 phenylallylidene]chromans 3a-e, and (E)-3-(3-phenylprop-1-en-1-yl)-2H-chromenes 4a-d were designed and synthesized. All the compounds were tested in vitro for their efficacy against infection by human rhinovirus (HRV) 1B and 14, two representative serotypes for rhinovirus group B and A, respectively. Most of the analogues were found to be potent and selective inhibitors of both HRVs, although HRV 1B was generally more susceptible than HRV 14. Mechanism of action studies of (E)-6-chloro-3-(3-phenylprop-1-en-1-yl)-2H-chromene 4b, the most potent compound on HRV 1B infection, suggested that 4b behaves as a capsid-binder probably acting at the uncoating level. PMID- 22088307 TI - Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent. AB - Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in the development of an array of inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis and sepsis. The synthesis of MIF-inhibitor is a rationale approach to develop novel anti-inflammatory agent to treat multitude of inflammatory diseases. In this work, we have synthesized and evaluated MIF-inhibitory activity of a series of small molecules containing isoxazoline skeleton. Mode of binding of this inhibitor to human MIF (huMIF) was determined by docking studies. The synthesized molecules inhibit tautomerase activity of huMIF. The anti-inflammatory activity of the most active inhibitor, 4-((3-(4-hydroxy-3-methoxyphenyl)-4, 5 dihydroisoxazol-5-yl) methoxy) benzaldehyde (4b) was evaluated against huMIF induced inflammation in a cellular model (RAW 264.7 cell). Compound 4b significantly inhibits huMIF-mediated NF-kappaB translocation to the nucleus, up regulation of inducible nitric oxide synthase and nitric oxide production in RAW 264.7 cell which are the markers for inflammation. The compound 4b is not cytotoxic as evident from cell viability assay. Hence, the compound 4b has potential to be a novel anti-inflammatory agent. PMID- 22088308 TI - Modification of olivomycin A at the side chain of the aglycon yields the derivative with perspective antitumor characteristics. AB - A novel way of chemical modification of the antibiotic olivomycin A (1) at the side chain of the aglycon moiety was developed. Interaction of olivomycin A with the sodium periodate produced the key acid derivative olivomycin SA (2) in 86% yield. This acid was used in the reactions with different amines in the presence of benzotriazol-1-yl-oxy-trispyrrolidino-phosphonium hexafluorophosphate (PyBOP) or diphenylphosphoryl azide (DPPA) to give corresponding amides. Whereas olivomycin SA was two orders of magnitude less cytotoxic than the parent antibiotic, the amides of 2 demonstrated a higher cytotoxicity. In particular, N,N-dimethylaminoethylamide of olivomycin SA showed a pronounced antitumor effect against transplanted experimental lymphoma and melanoma and a remarkably high binding constant to double stranded DNA. The therapeutic effects of this derivative were achievable at tolerable concentrations, suggesting that modifications of the aglycon's side chain, namely, its shortening to methoxyacetic residue and blocking of free carboxyl group, are straightforward for the design of therapeutically applicable derivatives of olivomycin A. PMID- 22088309 TI - Synthesis and study of new paramagnetic resveratrol analogues. AB - New resveratrol analogues containing five- and six-membered nitroxides and isoindoline nitroxides were synthesized. These new compounds were compared to resveratrol based on their ABTS radical scavenging ability as well on their capacity to suppress inflammatory process in macrophages induced by lipopolysaccharides. The ABTS and ROS scavenging activities of new molecules were the same or weaker than that of resveratrol, but some of paramagnetic resveratrol derivatives suppressed nitrite and TNFalpha production more efficiently than resveratrol. Based on these results the new nitroxide and phenol containing hybrid molecules can be considered as new antioxidant and anti-inflammatory agents. PMID- 22088310 TI - Cranberry components for the therapy of infectious disease. AB - Summary of the in vitro data support a beneficial effect of cranberry or its proanthocyanin constituents by blocking adhesion to and biofilm formation on target tissues of pathogens. In vivo data partially support these beneficial effects. Consumption of various cranberry products benefited young and elderly females in preventing urinary tract infections, and in conjunction with antibiotic treatment in eradicating Helicobacter pylori infections in women. Mouthwash supplemented with an isolated cranberry derivative reduced significantly the caryogenic mutans streptococci. None of the mice infected intranasal with lethal dose of influenza virus and treated with cranberry fraction died after two weeks. Further studies should focus on the active cranberry component as supplement for food and other products especially where whole juice or powder cannot be used. PMID- 22088312 TI - Adolescent depressive symptoms and subsequent pregnancy, pregnancy completion and pregnancy termination in young adulthood: findings from the victorian adolescent health cohort study. AB - STUDY OBJECTIVE: To examine relationships between depressive symptoms in adolescence (14-18 years of age) and becoming pregnant, completing a pregnancy (live birth) and terminating a pregnancy in young adulthood (21-24 years of age). PARTICIPANTS AND DESIGN: Data from 1000 females were drawn from a larger sample of 1943 young Australians participating in a longitudinal study of adolescent health and development, followed across 8 waves from adolescence (waves 1-6) to young adulthood (waves 7 and 8). SETTING: Victoria, Australia. MAIN OUTCOME MEASURES: Pregnancy, pregnancy completion and pregnancy termination between 21-24 years of age. RESULTS: We observed a twofold increase in the odds of becoming pregnant in those reporting persisting patterns of depressive symptoms during adolescence (2+ waves); however, after staged adjustment for adolescent antisocial behaviour, drug use and socioeconomic disadvantage, there was no evidence of association. Of particular note, and consistent with previous research, adolescent antisocial and drug use behavior were strongly associated with becoming pregnant and pregnancy termination in young adulthood. CONCLUSIONS: Adolescent antisocial and drug use behavior, not depressive symptoms, independently predict pregnancy outcomes in young adulthood. PMID- 22088313 TI - Adolescent caesarean delivery in the US military health care system. AB - OBJECTIVES: Determine cesarean delivery (CD) rates and associated demographics among military dependent teenagers. METHODS: United States military health care claims records of live births from 2003-2006 to 13- through 19-year-old dependent children were analyzed using logistic regression. RESULTS: The CD rate rose from 17% in 2003 to 20% in 2006. Rates were significantly higher for ages 18 and 19, for African American sponsors' children, and those who gave birth in a civilian facility. Rates did not differ significantly by sponsor's military rank. CONCLUSIONS: Teenagers in the military health care system have increasing rates of CD. Independent demographic risk factors for teenage CD include age > 17 years, sponsor's race African American, and delivery at a civilian facility. PMID- 22088311 TI - Cervical pap screening cytological abnormalities among HIV-infected adolescents in the LEGACY cohort. AB - OBJECTIVES: To determine the prevalence of cervical Pap screening (CPAP-S), identify factors associated with CPAP-S, and explore risk factors for abnormal cervical cytology in female adolescents with perinatally and behaviorally acquired HIV infection. DESIGN: Cross-sectional. SETTING: LEGACY is a national observational cohort chart review study of 1478 HIV-infected persons (= 95th percentile) but otherwise healthy female adolescents (10 black and 12 white; age range 8.8-13.9 y) who underwent adrenocorticotropic hormone stimulation testing at an academic medical center as part of a protocol for the study of obesity-related conditions. MAIN OUTCOME MEASURES: Basal and stimulated androgen levels. RESULTS: White and black participants were similar with regard to pubertal stage, body mass index, percentage body fat, and fasting glucose and insulin levels. Black girls had lower stimulated levels of 17-hydroxyprogesterone, and the differences between basal and stimulated levels of 17-hydroxyprogesterone and androstenedione were lower in black girls. Body mass index was negatively correlated with stimulated cortisol in blacks only (r = -0.69, P = .03). CONCLUSION: There appear to be race related differences in stimulated androgen levels in obese adolescent females. These differences deserve further study, as measurements of androgen levels are commonly used in clinical practice and research. PMID- 22088318 TI - Congenital paraurethral cysts in two newborn girls: differential diagnosis, management strategies, and spontaneous resolution. AB - BACKGROUND: At least five types of interlabial masses of different etiologies may present in a female neonate. The more serious type of interlabial mass must be differentiated from the benign and self-resolving paraurethral or hymenal cyst. Clues include appearance and color of the mass and the location of the mass in relation to the urethral meatus and the vaginal opening. Clinicians should be able to distinguish lesions that require aggressive intervention, i.e. surgery, from those that self-resolve and merely require observation. CASE: Two unrelated newborn girls each had a protruding faint-yellow-colored spherical interlabial cyst. The cyst was located anterior to the vaginal orifice and partially obscured the urethral meatus. Neither girl had any voiding problems. No other congenital anomalies were detected. Both cysts resolved rapidly and completely without surgical intervention. SUMMARY AND CONCLUSION: Paraurethral cysts of the newborn and hymenal cysts rarely cause urinary obstruction or spotting, and are self resolving. When positively identified, no evaluation of upper urinary tract is required and neither aspiration of cyst contents or marsupialization procedure is necessary. PMID- 22088319 TI - OsmC proteins of Mycobacterium tuberculosis and Mycobacterium smegmatis protect against organic hydroperoxide stress. AB - Bacterial antioxidants play a critical role in the detoxification of endogenously and host derived oxidative radicals during host-pathogen interactions. Recently, the osmotically induced bacterial protein C (OsmC) is included in the antioxidant category of enzymes as it shows structural and functional relationships with organic hydroperoxide reductase (Ohr) enzyme. A copy of the gene encoding OsmC is conserved across mycobacterial species, including Mycobacterium tuberculosis (Rv2923c) and Mycobacterium smegmatis (MSMEG2421), but its role in protecting these species against oxidative stress is unknown. To determine the role of OsmC in mycobacterial oxidative stress, we overexpressed and purified OsmCs of M. tuberculosis and M. smegmatis and assessed their ability to reduce peroxide substrates like hydrogen peroxide (H(2)O(2)), cumene hydroperoxide (CHP) and t butyl hydroperoxide (t-BHP) in Ferrous Ion Oxidation in Xylenol (FOX) assay. This revealed that OsmCs from both species were capable of reducing both inorganic (H(2)O(2)) and organic (CHP and t-BHP) peroxides. Further, an M. smegmatis mutant (MS?osmC) deficient in OsmC exhibited reduced reduction of CHP and t-BHP than the parental wild type strain, indicating that OsmC protein contributes significantly for the total peroxide reductase activity of mycobacteria. The MS?osmC strain was also sensitive to organic hydroperoxides, which could be reversed by complementing with a plasmid borne osmC. Plasmid borne osmC also increased the resistance of M. smegmatis wild type strain to isoniazid (INH) but at a relatively lower level than ahpC, an organic hydroperoxide reductase. These results suggest that OsmC plays an important role in peroxide metabolism and protecting mycobacteria against oxidative stress. PMID- 22088320 TI - Comparing efficacy of BCG/lactoferrin primary vaccination versus booster regimen. AB - Lactoferrin is an iron binding glycoprotein possessing multiple immune modulatory activities, including ability to affect macrophage cytokine production, promote maturation of T- and B-lymphocyte and immature dendritic cells, and enhance the ability of macrophages and dendritic cells to stimulate antigen-specific T-cells. These characteristics of lactoferrin suggested that it could function as an effective adjuvant enhance efficacy of the BCG, the current vaccine for tuberculosis disease. Admix of lactoferrin to the BCG vaccine promoted host protective responses that surpasses activity of the BCG vaccine alone as determined by decreasing pulmonary pathology upon challenge with virulent Mycobacterium tuberculosis (MTB). This study builds on previous reports by examining the effectiveness of the lactoferrin adjuvant comparing primary vaccination versus an immunization schedule with a booster administered at 8 weeks. BCG/lactoferrin vaccinating, given once or twice, demonstrated an improvement in pulmonary disease compared to both the BCG vaccinated and non immunized groups. The splenic recall profiles showed a difference in cytokine production induced by mycobacterial antigen from splenocytes isolated from mice immunized with BCG/lactoferrin once or twice. Production of IL-17 is increased in the BCG/lactoferrin 2* group compared to the primary vaccinated group. Both BCG/lactoferrin vaccinated group exhibited increase production of IFN-gamma compared to the non-immunized group and decreased production of IL-10 compared to the group vaccinated with only BCG. This study illustrates that the adjuvant activity of lactoferrin to enhance BCG efficacy occurs whether the vaccination regimen is a single delivery or combined with a booster, leading to enhanced host protection and decreased disease manifestation. PMID- 22088321 TI - Rapid DNA extraction for specific detection and quantitation of Mycobacterium tuberculosis DNA in sputum specimens using Taqman assays. AB - Rapid tuberculosis (TB) detection is critical for disease control, and further quantitation of Mycobacterium tuberculosis (Mtb) in sputum is valuable for epidemiological and clinical studies. We evaluated a simple, robust and cost efficient in-house DNA extraction and downstream Taqman approach for detection and quantitation of Mtb genomes from sputum of newly-diagnosed TB patients and non-TB controls. DNA was extracted using guanidine isothiocyanate and silica based spin columns in less than 2 h, stored frozen, and Taqman assays were used to detect Mtb with IS6110 and quantify it targeting RD1 and IS1081. The Taqmans had a sensitivity >95% in 108 culture-confirmed TB patients and specificity of 100% in 43 non-TB controls. Genome counts were correlated with the Mycobacterial Growth Indicator Tubes' (MGIT) time-to-detection values (1/TTD * 1000; rho = 0.66; p < 0.001) in 91 TB patients (33 excluded with MGIT contamination). This linear relationship was nearly identical between mycobacteria isolated from sputum and H37Rv Mtb grown in-vitro to its log phase. TB treatment between 3 and 7 days was associated with lower 1/TTD * 1000 values but not with genome counts. Together, our protocol provides rapid, specific, inexpensive and quantitative detection of Mtb DNA in fresh or stored sputa making it a robust tool for prompt TB diagnosis, and with potential use for clinical and epidemiologic studies. PMID- 22088322 TI - Prolonged survival of scavenger receptor class A-deficient mice from pulmonary Mycobacterium tuberculosis infection. AB - The present study tested the hypothesis that the scavenger receptor SR-A modulates granuloma formation in response to pulmonary infection with Mycobacterium tuberculosis (MTB). To test this hypothesis, we monitored survival and histopathology in WT and SR-A-deficient mice following aerosol infection with MTB Rv. SR-A-deficient (SR-A-/-) mice infected with MTB survived significantly longer than WT mice; the mean survival of SR-A-/- mice exceeded 430 days compared to 230 days for WT mice. Early granuloma formation was not impaired in SR-A-/- mice. The extended survival of SR-A-/- mice was associated with 13- and 3-fold higher number of CD4+ lymphocytes and antigen presenting cells in SR-A-/- lungs compared to WT mice 280 after infection. The histopathology of chronically infected SR-A-/- lungs, however, was marked by abundant cholesterol clefts in parenchymal lesions containing infection in multinucleated giant cells. The present study indicates SR-A as a candidate gene of the innate immune system influencing the chronic phase of M. tuberculosis infection. PMID- 22088323 TI - Giving TB wheels: Public transportation as a risk factor for tuberculosis transmission. AB - Previous geospatial analysis of the well-defined Houston Tuberculosis Initiative (HTI) database identified an association between the use of city-bus transportation (inclusive of time onboard) and Tuberculosis (TB) incidence in Houston/Harris County census tracts (paper submitted). This paper is an extension of those findings. Contact investigations on school buses have reported a high rate of positive tuberculin skin tests in the persons traveling with the index case and have shown an association with bus ride duration. In Houston, city bus routes are veins connecting even the most diverse of populations within the metropolitan area. Among HTI participants, TB patients who reported weekly bus use were more likely to have demographic and social risk factors associated with poverty, immune suppression and health disparities. An equal proportion of bus riders and non-bus riders were cultured for Mycobacterium tuberculosis (MTB), yet 75% of bus riders were clustered with a mean cluster size of 50.14, indicating recent transmission, compared to 56% of non-bus riders (OR = 2.4, p < 0.001) with a mean cluster size of 28.9 (p < 0.01). Individual bus routes, including one route servicing the local hospitals, were found to be risk factors for endemic MTB clustered strains and the routes themselves geographically connect the census tracts previously identified as having endemic TB. PMID- 22088324 TI - A quality assessment tool for tuberculosis control activities in resource limited settings. AB - Tuberculosis (TB) is a significant problem, infecting nearly 9 million new patients per year and killing about 2 million a year. The primary means with which to affect TB globally are to decrease transmission locally, mainly by effective identification, diagnosis, and treatment of infectious TB patients. Therefore, quality assurance of TB control efforts at the local level is essential. This study describes the creation of a data extraction tool for retrospective chart review based on the International Standards for TB Care, 2009 for the assessment of TB control programs located in resource limited settings. The tool was field tested at a rural mission hospital in central Kenya. Results were used by host site staff to develop a quality improvement plan. The process prompted revision of the tool to clarify questions and answers. This is a tool that can be used in resource limited settings for data collection to assess the quality of TB care and to inform the design, implementation, and further assessment of future quality improvement initiatives. PMID- 22088325 TI - Primary care direct access MRI for the investigation of chronic headache. AB - AIM: To assess the efficacy of a primary-care imaging pathway for neurology outpatients, from inception to deployment, compared with traditional outpatient referral. MATERIALS AND METHODS: After local agreement, guidelines were generated providing pathways for diagnosis and treatment of common causes of headache, highlighting "red-flag" features requiring urgent neurology referral, and selecting patients for direct magnetic resonance imaging (MRI) referral. In addition, reports were clarified and standardized. To evaluate the efficacy of the access pathway, a retrospective sequential review of 100 MRI investigations was performed comparing general practitioner (GP) referral, with traditional neurology referral plus imaging, acquired before the pathway started. RESULTS: No statistically significant difference in rates of major abnormalities, incidental findings or ischaemic lesions were identified between the two cohorts. Reported patient satisfaction was high, with a cost reduction for groups using the pathway. CONCLUSION: The findings of the present study suggest that a defined access pathway for imaging to investigate chronic headache can be deployed appropriately in a primary-care setting. PMID- 22088326 TI - Where do locking screws purchase in the humeral head? AB - INTRODUCTION: One of the limiting factors in finding the best osteosynthesis approach in proximal humerus fractures is the current lack of information on the properties of the cancellous bone regions engaged by the implants fixing the epiphysis. The aim of this study is to assess the densitometric and mechanical characteristics of these regions when using a proximal humerus locking plate (PHLP). MATERIALS AND METHODS: Nineteen PHLPs were mounted on cadaveric humeri using only their three most distal screws. Subsequently, the plates were removed and the bones were scanned using high-resolution peripheral quantitative computed tomography. Bone mineral density (BMD) was determined in the intact proximal epiphysis and in the exact locations where the six proximal screws would have been positioned concluding the instrumentation. Each plate was then repositioned on its bone and a minimally destructive local torque measurement was performed in the same six locations. A statistical analysis was performed to detect significant differences in the investigated parameters between screw positions, and to test the ability of local torque values to discriminate the bone mineral density of the entire humeral head (BMD(TOT)). RESULTS: Novel data about the cancellous bone engaged by the screws of a PHLP are provided. Different epiphyseal locations showed statistically significant different properties. A local torque measurement was a good predictor of the BMD(TOT). CONCLUSION: Position and direction of the epiphyseal screws on a locking implant are determinant to engage bone regions with significantly better bone quality. A breakaway torque measurement in a given screw position can distinguish between humeral heads with different densitometric properties. PMID- 22088327 TI - Vitamin D levels in post-menopausal Korean women with a distal radius fracture. AB - INTRODUCTION: The purpose of this study was to investigate serum levels of vitamin D in post-menopausal Korean women with a distal radius fracture (DRF) and to determine if there is any association between vitamin D levels and bone related variables such as bone mineral densities (BMDs), serum parathyroid hormone (PTH) levels and several bone turnover markers. MATERIALS AND METHODS: The data of 104 postmenopausal women surgically treated for a distal radius fracture (DRF group) and 107 age-matched control patients without a fracture (control group) were compared. Serum vitamin D levels (25-hydroxycholecalciferol, 25(OH)D(3)) were compared between the groups with consideration of age and seasonal variations. BMDs, serum PTH and several bone turnover markers, including serum osteocalcin, C-telopeptide and urine N-telopeptide, were measured and analysed to find any association with vitamin D levels. RESULTS: The mean 25(OH)D(3) level was significantly lower in the DRF group compared to the control group (p < 0.001). In particular, patients in their sixth and seventh deciles in the DRF group had significantly lower 25(OH)D(3) levels than patients in the control group (p = 0.001 and 0.013, respectively). When seasonal variation was considered, significant differences of 25(OH)D(3) levels were found between the groups in autumn and winter. Hip BMDs were significantly lower in the DRF group than in the control group, and there was a positive correlation between serum 25(OH)D(3) levels and hip BMDs. Bone turnover markers were not significantly different between the two groups, although serum PTH levels were marginally higher in the DRF group (p = 0.08). CONCLUSIONS: Post-menopausal Korean women with a DRF were found to have significantly lower serum vitamin D levels than the control group, and vitamin D levels were particularly lower in women in their sixth and seventh deciles who may be a good target group for prevention of future fractures. Future investigation should focus on determining whether vitamin D supplementation can be helpful in preventing future fractures in patients with a DRF. PMID- 22088328 TI - Effects of microcystin-LR exposure on matrix metalloproteinase-2/-9 expression and cancer cell migration. AB - This study assessed the effects of microcystin-LR (MC-LR) exposure on matrix metalloproteinases (MMPs) expression and cancer cell migration. After male mice were orally administered with different concentrations of MC-LR for 270 d, histopathologic observation revealed an obvious hepatic lymphocyte infiltration or fatty degeneration. Immunohistochemical staining and enzyme-linked immunosorbent assay demonstrated that MC-LR treatment (even at 1 nM) caused up regulated expressions of hepatic MMP-2/-9. Quantitative reverse-transcriptase PCR showed that the exposure to 80 nM MC-LR induced an increase of MMP-2/-9 mRNA levels by 1.0 and 1.9 fold. Breast cancer cells (MDA-MB-435s) were also cultured with MC-LR solutions and a wound healing assay demonstrated that MC-LR posed a time/dose-dependent stimulation effect on migration of the cancer cells. Gelatin electrophoresis and quantitative PCR showed significant increases in cellular MMP 2/-9 expressions after MC-LR exposure. This study indicated that chronic exposure to MC-LR could alter MMP-2/-9 expressions and stimulate cancer cell migration. PMID- 22088329 TI - An in situ test to explore the responses of Scenedesmus acutus and Lepocinclis acus as indicators of the changes in water quality in lowland streams. AB - This bioassay was designed with the aim of exploring the responses of two wild planktonic microalgae exposed in situ (72 h) as indicators of the changes in water quality. Monocultures of both strains within dialysis membrane bags were placed at two sites in a small lowland stream. Site 1 is located at a suburban area with low horticultural activity and Site 2 is impacted by toxic industrial discharges and urban land use. There was a decrease in population growth of both species at Site 2 compared with Site 1. The comparison of the algae exposed in situ with the normal specimens cultured at the laboratory indicated a significant increase in the cellular volume for both species at both sites. Abnormal shape was recorded at both sites, the percentage being significantly greater for Scenedesmus acutus at Site 2. Significant changes in pyrenoids size were observed in S. acutus and in the percentage of fragmented nuclei in Lepocinclis acus. Also in the latter abnormal paramylon grains were observed. These responses were accentuated at Site 2. This bioassay was sensitive, short term, low cost, and therefore is a suitable tool to contribute with the monitoring and ecological risk assessment of lowland streams. PMID- 22088330 TI - Biphasic effects of lanthanum on Vicia faba L. seedlings under cadmium stress, implicating finite antioxidation and potential ecological risk. AB - In the present study, lanthanum (La) as a representative REE was used to explore the mechanisms for alleviation of Cd-induced oxidative damage by extraneous La at appropriate concentrations, and to assess ecological risk of combination of Cd and La at higher concentrations in roots of Vicia faba L. seedlings. The seedlings were hydroponically cultured for 15 d under nutrient solution, 6 MUmol L(-1) CdCl(2), and combination of 6 MUmol L(-1) CdCl(2) and increasing concentrations of La, respectively. The results showed that the supplementation with low concentrations of exogenous La (<120 MUmol L(-1)) led to reduced contents of Cd, Ca, Cu, Zn, Mn or Fe element and increased activities of superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (GPX) and ascorbate peroxidase (APX) isozymes as well as heat shock protein 70 (HSP 70) production in the roots. However, the supplementation with higher La (>120 MUmol L(-1)) showed the adverse effects. The contents of Cd elevated above the single Cd treatment in the roots, accompanying with the decline of antioxidant isozyme's activities and HSP 70, and increment of carbonylated proteins and endoprotease isozyme's activities. The results also showed that the root growth was not only related to carbonylated proteins, but also to indole acetic acid oxidase activities. Therefore, the supplemented extraneous La contributed to biphasic effects: stimulated antioxidation at lower concentrations and pro-oxidation at higher concentrations against Cd-induced oxidative stress in the roots. PMID- 22088331 TI - The cost-effectiveness of immediate treatment, percutaneous biopsy and active surveillance for the diagnosis of the small solid renal mass: evidence from a Markov model. AB - PURPOSE: The most effective diagnostic strategy for the very small, incidentally detected solid renal mass is uncertain. We assessed the cost-effectiveness of adding percutaneous biopsy or active surveillance to the diagnosis of a 2 cm or less solid renal mass. MATERIALS AND METHODS: A Markov state transition model was developed to observe a hypothetical cohort of healthy 60-year-old men with an incidentally detected, 2 or less cm solid renal mass, comparing percutaneous biopsy, immediate treatment and active surveillance. The primary outcomes assessed were the incremental cost-effectiveness ratio measured by cost per life year gained at a willingness to pay threshold of $50,000. Model results were assessed by sensitivity analysis. RESULTS: Immediate treatment was the highest cost, most effective diagnostic strategy, providing the longest overall survival of 18.53 life-years. Active surveillance was the lowest cost, least effective diagnostic strategy. On cost-effectiveness analysis using a societal willingness to pay threshold of $50,000 active surveillance was the preferred choice at a $75,000 willingness to pay threshold while biopsy and treatment were acceptable ($56,644 and $70,149 per life-year, respectively). When analysis was adjusted for quality of life, biopsy dominated immediate treatment as the most cost-effective diagnostic strategy at $33,840 per quality adjusted life-year gained. CONCLUSIONS: Percutaneous biopsy may have a greater role in optimizing the diagnosis of an incidentally detected, 2 cm or less solid renal mass. PMID- 22088332 TI - Comparative outcomes of pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation in patients treated with radical cystectomy. AB - PURPOSE: We compared clinical outcomes, and identified predictors of cancer specific and overall survival after radical cystectomy in patients with urothelial carcinoma with squamous differentiation and those with pure squamous cell carcinoma. MATERIALS AND METHODS: We reviewed data on 2,031 patients treated with radical cystectomy and pelvic lymph node dissection at a single high volume referral center. Of these patients 78 had squamous cell carcinoma and 67 had squamous differentiation. Survival estimates by histological subtype were described using Kaplan-Meier methods. Within histological subtypes pathological stage, nodal invasion, soft tissue margins, age and gender were evaluated as predictors of cancer specific survival and overall survival using univariate Cox regression. RESULTS: Median followup was 44 months. Of 104 patient deaths 60 died of their disease. We did not find a statistically significant difference between survival curves of patients with squamous cell carcinoma and squamous differentiation (log rank overall survival p = 0.6, cancer specific survival p = 0.17). Positive soft tissue margins were associated with worse cancer specific survival (HR 6.92, 95% CI 2.98-16.10, p <=0.0005) and overall survival (HR 3.68, 95% CI 1.84-7.35, p <=0.0005) in patients with pure squamous cell carcinoma. Among patients with squamous differentiation, pelvic lymphadenopathy was associated with decreased overall survival (HR 2.52, 95% CI 1.33-4.77, p = 0.004) and cancer specific survival (HR 3.23, 95% CI 1.57-6.67, p = 0.002). CONCLUSIONS: There appears to be no evidence of a difference in cancer specific survival or overall survival between patients with squamous cell carcinoma and those with squamous differentiation treated with radical cystectomy and pelvic lymph node dissection. Patients with squamous differentiation and tumor metastases to pelvic lymph nodes should be followed more closely, and adjuvant treatment should be considered to improve survival. Wide surgical resection is critical to achieve local tumor control and improve survival in patients with squamous cell carcinoma. PMID- 22088333 TI - Influence of renal excretory function on the performance of urine based markers to detect bladder cancer. AB - PURPOSE: In hematuria cases urine based tests are used to detect bladder cancer, although the diagnostic yield remains insufficient due to influencing variables, including urinary tract infection. Many patients are elderly with renal insufficiency and have proteinuria as an additional influencing factor. To our knowledge no data are available on the accuracy of urine based bladder cancer tests in conjunction with renal function. MATERIALS AND METHODS: Urine samples of 449 patients with hematuria and histology were included in analysis. Cytology, fluorescence in situ hybridization, immunocytology and nuclear matrix protein 22 assay were done. Renal function was classified as normal, impaired or severely impaired based on serum creatinine, the glomerular filtration rate and proteinuria. False-positive rates were statistically compared in regard to renal function. RESULTS: A total of 382 patients did not have bladder cancer. There was an increased false-positive rate for creatinine and the glomerular filtration rate. The nuclear matrix protein 22 test showed a 22.0% and 46.7% false-positive rate in the normal and limited function cohorts, respectively (p = 0.05). Similar trends were noted for proteinuria. Indeterminate significance was detected, separating those with severely impaired function for immunocytology and those in the normal group for fluorescence in situ hybridization (p = 0.08 and 0.06, respectively). Proteinuria was a significant factor for urine cytology with increased false-positive results in the absence of urinary tract infection (p = 0.0017 and 0.05, respectively). CONCLUSIONS: To our knowledge this is the first study of renal function and the accuracy of urine based bladder cancer markers. Renal function influences the diagnostic yield. A decreased glomerular filtration rate was associated with increased false-positive nuclear matrix protein 22 results while proteinuria decreased urine cytology specificity. Renal function should be considered when urine based bladder cancer tests are interpreted. PMID- 22088334 TI - Utilization trends at a multidisciplinary prostate cancer clinic: initial 5-year experience from the Duke Prostate Center. AB - PURPOSE: The multidisciplinary approach is becoming increasingly encouraged but little is known about the multidisciplinary experience compared to routine care. For patients with prostate cancer the goal is to provide evaluations by urologists, medical and radiation oncologists at a single visit. Although additional resources are required, this strategy may enhance the overall health care experience. We compared utilization determinants between a multidisciplinary and a urology prostate cancer clinic at Duke University Medical Center and identified factors associated with pursuing treatment at the university medical center for multidisciplinary clinic patients. MATERIALS AND METHODS: We retrospectively analyzed data on patients referred for primary prostate cancer treatment evaluation at Duke University Medical Center from 2005 to 2009. Comparisons between 701 multidisciplinary clinic and 1,318 urology prostate cancer clinic patients were examined with the rank sum and chi-square tests. Predictive factors for pursuing treatment at the university medical center were assessed using multivariate adjusted logistic regression. RESULTS: Compared to patients at the urology prostate cancer clinic those at the multidisciplinary clinic were more likely to be younger and white, have a higher income and travel a longer distance for evaluation. Of multidisciplinary clinic patients 58% pursued primary treatment at the university medical center. They were more likely to be younger, black and physician referred, have a lower income and reside closer to the medical center. Factors predictive of pursuing treatment at the medical center included high risk disease and physician referral. Factors predictive of not receiving care at the university medical center were income greater than $40,000 and a distance traveled of greater than 100 miles. CONCLUSIONS: A different patient demographic is using the multidisciplinary approach. However, when treatment is pursued at the institution providing multidisciplinary services, the patient demographic resembles that of the treating institution. PMID- 22088335 TI - Clinical and pathological features associated with prognosis in patients with papillary renal cell carcinoma. AB - PURPOSE: We determined the clinical and pathological features associated with death from papillary renal cell carcinoma in 395 surgically treated patients. MATERIALS AND METHODS: Papillary renal cell carcinoma tissue slides from each patient were reviewed for type (1 or 2), grade, TNM stage, coagulative tumor necrosis and sarcomatoid differentiation. Associations of clinical and pathological features with death from renal cell carcinoma were evaluated using Cox proportional hazards regression models and summarized by the HR and 95% CI. Cancer specific survival was estimated using the Kaplan-Meier method. RESULTS: Univariate analysis revealed that symptoms, tumor thrombus, tumor size, perinephric/renal sinus fat invasion, 2010 primary tumor classification, regional lymph node involvement, distant metastasis, 2010 TNM stage group, grade, tumor necrosis, sarcomatoid differentiation and papillary renal cell carcinoma type were associated with death from renal cell carcinoma. Grade was more strongly associated with death from renal cell carcinoma than papillary renal cell carcinoma type. Multivariate analysis indicated that symptoms, 2010 TNM stage group and grade jointly were significantly associated with death from renal cell carcinoma. CONCLUSIONS: This large series of patients with papillary renal cell carcinoma reveals features associated with death from renal cell carcinoma and confirms that grade is more predictive of outcome than papillary renal cell carcinoma type. PMID- 22088336 TI - Incidental detection of renal cell carcinoma is an independent prognostic marker: results of a long-term, whole population study. AB - PURPOSE: The true effect of incidental detection on the survival of patients with renal cell carcinoma has been debated. We used centralized databases in Iceland to study prognostic factors of survival, focusing on the effect of incidental detection. MATERIALS AND METHODS: This retrospective study included all living patients diagnosed with renal cell carcinoma in Iceland from 1971 to 2005. Hospital charts and histology were reviewed. Incidentally diagnosed renal cell carcinomas were compared to symptomatic tumors and prognostic factors were evaluated using Cox multivariate analysis. RESULTS: Of the 910 patients 254 (27.9%) were diagnosed incidentally, most often by abdominal ultrasound (29.5%) or computerized tomography (28.3%). The incidental detection rate increased from 11.1% in 1971 through 1975 to 39.2% in 2001 through 2005 (p <0.001). During the same period the incidence increased significantly in males but in females only during the last 5 study years. Mortality remained unchanged for each gender. Incidentally detected tumors were an average of 2.6 cm smaller and diagnosed at lower stage and lower grade than symptomatic tumors. Age and histology were similar in each group. TNM stage was by far the strongest independent prognostic factor of survival but age, calendar year of diagnosis and ESR were also significant. After correcting for confounders patients with symptomatic renal cell carcinoma had worse survival than those diagnosed incidentally. CONCLUSIONS: With increased incidence and unchanged mortality the survival of patients with renal cell carcinoma has improved. This is mainly related to a steep increase in incidental detection. Incidental detection affects survival favorably and to a greater extent than can be explained by lower stage compared to the survival of patients diagnosed with symptoms. PMID- 22088337 TI - The population level prevalence and correlates of appropriate and inappropriate imaging to stage incident prostate cancer in the medicare population. AB - PURPOSE: According to guidelines most men with incident prostate cancer do not require staging imaging. We determined the population level prevalence and correlates of appropriate and inappropriate imaging in this cohort. MATERIALS AND METHODS: We performed a cross-sectional study of men 66 to 85 years old who were diagnosed with prostate cancer in 2004 and 2005 from the SEER (Surveillance, Epidemiology and End Results)-Medicare database. Low risk (no prostate specific antigen greater than 10 ng/ml, Gleason score greater than 7 or clinical stage greater than T2) and high risk (1 or more of those features) groups were formed. Inappropriate imaging was defined as any imaging for men at low risk and appropriate imaging was defined as bone scan for men at high risk as well as pelvic imaging as appropriate. Logistic regression modeled imaging in each group. RESULTS: Of 18,491 men at low risk 45% received inappropriate imaging while only 66% of 10,562 at high risk received appropriate imaging. For patients at low risk inappropriate imaging was associated with increasing clinical stage (T2 vs T1 OR 1.35, 95% CI 1.27-1.44), higher Gleason score (7 vs less than 7 OR 1.80, 95% CI 1.69-1.92), increasing age and comorbidity as well as decreasing education. Appropriate imaging for men at high risk was associated with lower stage (T4, T3 and T2 vs T1 OR 0.63, 95% CI 0.48-0.82, OR 0.67, 95% CI 0.60-0.80 and OR 0.87, 95% CI 0.80-0.86) and with higher Gleason score (greater than 8 and 7 vs less than 7 OR 2.18, 95% CI 1.92-2.48 and 1.51, 95% CI 1.35-1.70, respectively) as well as with younger age, white race, higher income, lower stage and more comorbidity. CONCLUSIONS: We found poor adherence to imaging guidelines for men with incident prostate cancer. Understanding the patterns by which clinicians use imaging for prostate cancer should guide educational efforts as well as research to suggest evidence-based guideline improvements. PMID- 22088338 TI - Population based analysis of the increasing incidence of kidney cancer in the United States: evaluation of age specific trends from 1975 to 2006. AB - PURPOSE: An increase in kidney cancer was reported in the United States but overall rates may obscure trends in age specific groups. We explored whether the increase in kidney cancer incidence differs across age groups. MATERIALS AND METHODS: We ascertained the 63,843 incident renal cancer cases in SEER (Surveillance, Epidemiology and End Results) cancer registries for 1975 to 2006. Yearly incidence rates of renal cancer were calculated and stratified by age group. Age specific trends in cancer diagnosis were evaluated by Poisson regression. RESULTS: From 1975 to 2006 the overall age adjusted renal cancer incidence increased 238% from 7.4/100,000 to 17.6/100,000 adults. From 1991 to 2006 the mean age at diagnosis decreased from 64.7 to 62.7 years and the proportion of patients diagnosed before age 65 years increased from 45.9% to 55.3%. Age specific incidence rates of renal cancer increased in all age groups from 1975 to 2006 (p <0.0001). However, the rates changed at different rates. Overall renal cancer diagnosis in the youngest age group (20 to 39 years) increased more quickly than all other age groups (p <0.0001). The renal cancer incidence in patients 60 to 69 and 70 to 79 years old increased more rapidly than in those 40 to 49 and 50 to 59 years old (p <0.01). CONCLUSIONS: In the last 15 years mean age at diagnosis of renal cancer has decreased. During our study period the most rapidly increasing kidney cancer incidence was seen in those younger than 40 and 60 to 79 years old. The renal cancer increase in younger patients should direct attention toward further evaluation of renal cancer risk factors. PMID- 22088339 TI - A nomogram to predict the duration of drainage in patients with penile cancer treated with inguinal lymph node dissection. AB - PURPOSE: We developed a nomogram to predict the duration of drainage in patients with penile cancer treated with inguinal lymph node dissection. MATERIALS AND METHODS: A total of 111 groin basins in 56 patients who underwent radical inguinal lymph node dissection for penile cancer were retrospectively assessed. We retrieved the clinicopathological factors from the medical records including age, body mass index, albumin, smoking history, hypertension, diabetes, preoperative radiotherapy/chemotherapy, palpable lymph nodes, previous lymph node biopsy, total number of resected lymph nodes and ratio of positive lymph nodes. The criterion of drain removal was total drain output of 50 ml or less per day for 2 days starting from postoperative day 3. A multivariate Cox proportional hazards model was used to explore the risk factors of drainage duration and variable selection was performed according to Akaike's information criteria. A nomogram was built based on regression coefficients and internally validated with 200 bootstrap resamples. RESULTS: Median postoperative drainage duration was 7 days. The prediction model using pretreatment factors showed a concordance index of 0.55. With the addition of lymph node related variables a second model was constructed which produced a better concordance index (0.65) and good calibration. On multivariate analysis young age, high body mass index, total number of resected lymph nodes and ratio of positive lymph nodes were independent predictors of prolonged lymphatic drainage. CONCLUSIONS: On the basis of readily obtained clinicopathological variables we developed a nomogram to predict the duration of lymphatic drainage which, if externally validated, could be helpful for patient consultation, treatment decision making and clinical trial design. PMID- 22088341 TI - Urological manifestations of sarcoidosis. AB - PURPOSE: We describe the urological manifestations of sarcoidosis and how the disease may affect the management of multiple urological conditions. MATERIALS AND METHODS: We performed a PubMed(r) search using the query sarcoidosis and multiple urological terms. RESULTS: Sarcoidosis is a disease that has variable manifestations. There is often genitourinary involvement that is clinically silent. However, sarcoidosis may cause symptoms, such as nephrolithiasis, which are sometimes the first manifestation of the disease. Renal function may be affected, and appropriate recognition and treatment may avert progressive functional decline. The presence of sarcoidosis may also confound the diagnosis and staging of various urological malignancies, particularly renal and testicular carcinoma. CONCLUSIONS: Urologists should be aware of the urological manifestations of sarcoidosis to avoid misdiagnoses and the over staging of urological cancers, and to identify when it is an underlying cause of nephrolithiasis or obstructive uropathy. PMID- 22088340 TI - High dose brachytherapy as monotherapy for intermediate risk prostate cancer. AB - PURPOSE: We evaluated our retrospective, single institution experience with high dose rate brachytherapy as monotherapy for intermediate risk prostate cancer. MATERIALS AND METHODS: Our cohort included 284 patients with intermediate risk prostate cancer, defined as clinical stage T2b/T2c, Gleason score 7 and/or prostate specific antigen 10 to 20 ng/ml, and 1-year minimum followup. Treatment was 2 high dose rate brachytherapy sessions at 3 fractions of 6.5 Gy each for a mean of 19 days. Prostate specific antigen failure was defined as nadir +2 ng/ml. RESULTS: Mean followup was 35.1 months (median 31.9). Actuarial 5-year cause specific survival and clinical local control were 100%, distant-metastasis-free survival 98.8% and biochemical disease-free survival 94.4%. Clinical stage predicted biochemical disease-free survival. For stage T2a or less 5-year biochemical disease-free survival was 95.1% vs 100% for stage T2b and 77.4% for T2c (p = 0.012). Percent positive biopsy cores and prostate specific antigen nadir were also predictive. International Prostate Symptom Score results remained stable and potency was maintained in 82.6% of patients at 2 years. Pads were used for the first time after brachytherapy in 22 patients (7.7%), mostly for grade 1 incontinence (occasionally or less per week). Excluding patients with prior transurethral prostatectomy, stroke or tremor 2.5% used pads for the first time after treatment. No patient had urethral stricture. Radiation Therapy Oncology Group grade 1 rectal toxicity developed in 12 patients (4.2%) but not beyond grade 1. CONCLUSIONS: High dose rate brachytherapy as monotherapy is safe and effective for patients with intermediate risk prostate cancer. We recommend caution for percent positive biopsy cores exceeding 75% or clinical stage T2c. Excluding such patients the 5-year biochemical disease-free survival rate was 97.5%. PMID- 22088342 TI - A systematic review of the quality of evidence of ablative therapy for small renal masses. AB - PURPOSE: We critically assessed the methodological and reporting quality of published studies of ablative techniques for small renal masses. MATERIALS AND METHODS: We performed a systematic PubMed(r) and EMBASE(r) literature search from January 1966 to March 2010 to identify all full text, original research publications on ablative therapy for renal masses. Six reviewers working independently in 3 teams performed duplicate data abstraction using Strengthening the Reporting of Observational Studies in Epidemiology criteria, which were pilot tested in a separate sample. RESULTS: A total of 117 original research publications published in a 15-year period (1995 to 2009) met eligibility criteria. No randomized, controlled trials were identified. All studies were observational and 88.9% had 1 arm with no comparison group. Median sample size was 18 patients (IQR 5.5, 40.0) and 53.8% of studies included 20 or fewer patients. Median followup was 14.0 months (IQR 8.0, 23.8) and only 19.7% of studies had an average followup of greater than 24 months. Of the studies 20.5% mentioned the number of operators involved and only 6.0% provided information on their experience level. Of the studies 66.7% addressed the recurrence rate. Disease specific and overall survival was reported in only 15.4% and 16.2% of studies, respectively. CONCLUSIONS: The published literature on the therapeutic efficacy of ablative therapy for renal masses is largely limited to uncontrolled, 1-arm observational studies. In the absence of higher quality evidence ablative therapy outside research studies should be limited to select patients who are not candidates for surgical intervention. PMID- 22088343 TI - Bladder pain syndrome/interstitial cystitis in twin sisters. AB - PURPOSE: We determined the genetic contribution of and associated factors for bladder pain syndrome using an identical twin model. MATERIALS AND METHODS: Multiple questionnaires were administered to adult identical twin sister pairs. The O'Leary-Sant Interstitial Cystitis Symptom and Problem Index was administered to identify individuals at risk for bladder pain syndrome. Potential associated factors were modeled against the bladder pain syndrome score with the twin pair as a random effect of the factor on the bladder pain syndrome score. Variables that showed a significant relationship with the bladder pain syndrome score were entered into a multivariable model. RESULTS: In this study 246 identical twin sister pairs (total 492) participated with a mean age (+/- SD) of 40.3 +/- 17 years. Of these women 45 (9%) were identified as having a moderate or high risk of bladder pain syndrome (index score greater than 13). There were 5 twin sets (2%) in which both twins met the criteria. Correlation of bladder pain syndrome scores within twin pairs was estimated at 0.35, suggesting a genetic contribution to bladder pain syndrome. Multivariable analysis revealed that increasing age (estimate 0.46 [95% CI 0.2, 0.7]), irritable bowel syndrome (1.8 [0.6, 3.7]), physical abuse (2.5 [0.5, 4.1]), frequent headaches (1.6 [0.6, 2.8]), multiple drug allergies (1.5 [0.5, 2.7]) and number of self-reported urinary tract infections in the last year (8.2 [4.7, 10.9]) were significantly associated with bladder pain syndrome. CONCLUSIONS: Bladder pain syndrome scores within twin pairs were moderately correlated, implying some genetic component. Increasing age, irritable bowel syndrome, frequent headaches, drug allergies, self-reported urinary tract infections and physical abuse were factors associated with higher bladder pain syndrome scores. PMID- 22088344 TI - The impact of cyclooxygenase-2 and vascular endothelial growth factor C immunoexpression on the prognosis of penile carcinoma. AB - PURPOSE: We assessed the influence of cyclooxygenase-2 and vascular endothelium growth factor-C immunoexpression on groin metastasis and cancer survival, and their association with histological variables in patients with penile carcinoma. MATERIALS AND METHODS: We evaluated the histological and cyclooxygenase 2/vascular endothelium growth factor-C immunohistochemical profiles of patients with penile carcinoma treated at a single institution between 2001 and 2008. Univariate and multivariate analysis was done to determine the impact of histological and immunohistochemical markers on the risk of inguinal metastasis and on cancer survival. Survival analysis of relevant variables was also done. RESULTS: Of the 127 patients enrolled 76 and 30 had positive cyclooxygenase-2 and vascular endothelium growth factor-C immunoexpression, respectively. Univariate analysis identified an association between vascular endothelium growth factor-C immunoexpression and groin metastasis, and certain histological variables. Logistic regression showed that high tumor grade, Jackson stage and vascular endothelium growth factor-C immunoexpression were independent predictors of inguinal metastasis. Cancer survival was only influenced by advanced Jackson stage and groin metastasis. CONCLUSIONS: Findings suggest that vascular endothelium growth factor-C expression may help identify patients with an unfavorable clinical course of penile carcinoma. Cyclooxygenase-2 did not alter the risk of groin metastasis or cancer death. Inguinal disease and advanced Jackson stage were independent prognostic factors for worse cancer survival. PMID- 22088345 TI - Penile rehabilitation after radical prostatectomy: pro. PMID- 22088346 TI - Varicoceles and treatment of infertility--have we made any progress? PMID- 22088347 TI - Pediatric urology: a "grown-up" subspecialty. PMID- 22088348 TI - The usefulness of prostate cancer genome-wide association studies. PMID- 22088349 TI - To V(CUG) or not to V(CUG)--can we answer the question? PMID- 22088350 TI - Accuracy of sentinel lymph node biopsy for inguinal lymph node staging of penile squamous cell carcinoma: systematic review and meta-analysis of the literature. AB - PURPOSE: Sentinel lymph node biopsy is emerging as a promising method for inguinal lymph node staging of penile squamous cell carcinoma. In the current systematic review we evaluated the accuracy of sentinel lymph node biopsy for inguinal lymph node staging of penile squamous cell carcinoma and studied possible influential factors. MATERIALS AND METHODS: MEDLINE(r), Scopus(r), ISI(r), Ovid SP(r), Springer, ScienceDirect(r) and GoogleTM Scholar were searched by the key words "(penile OR penis) AND sentinel". No date or language limitation was imposed on the search and meeting abstracts were not excluded from analysis. A random effects model was used for statistical pooling. RESULTS: A total of 17 studies suitable for meta-analysis were detected. Three articles had 2 different subgroups of patients and each subgroup was considered as a separate study. Overall 18 studies (including the subgroups) were used for detection rate meta analysis and 19 for sensitivity meta-analysis. The pooled detection rate was 88.3% (95% CI 81.9-92.6). Pooled detection rate of 90.1% (95% CI 83.6-94.1) was calculated for the studies using blue dye and radiotracer. The pooled sensitivity was 88% (95% CI 83-92). The highest pooled sensitivity (92% [95% CI 86-96]) was in the studies using radiotracer and blue dye, and recruiting only cN0 cases. CONCLUSIONS: Sentinel lymph node mapping in penile squamous cell carcinoma is a method with a high detection rate and sensitivity. Using radiotracer and blue dye for sentinel lymph node mapping and including only cN0 disease ensures the highest detection rate and sensitivity. PMID- 22088351 TI - Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder using ultra performance liquid chromatography-ion mobility-mass spectrometry. AB - The elastin degradation products, desmosine (DES) and isodesmosine (IDES) are highly stable, cross-linking amino-acids that are unique to mature elastin. The excretion of DES/IDES in urine, in the free form and with associated peptide fragments, provides an indicator of lung damage in chronic obstructive pulmonary disease (COPD). A quantitative ion mobility-mass spectrometry (IM-MS) method has been developed for the analysis of free DES/IDES in urine with deuterated IDES as an internal standard. Resolution of DES/IDES isomers was achieved in less than five minutes using ultra performance liquid chromatography (UPLC) combined with ion pairing. The optimized UPLC-IM-MS method provided a linear dynamic range of 10-300 ng/mL and a limit of quantitation of 0.028 ng/mL for IDES and 0.03 ng/mL for DES (0.55 ng and 0.61 ng on column respectively). The method reproducibility (%RSD) was <4% for DES and IDES. The UPLC-IM-MS method was applied to the analysis of urine samples obtained from healthy volunteers and COPD patients. The DES/IDES concentrations in healthy and COPD urine showed an increase in DES (79%) and IDES (74%) in the COPD samples, relative to healthy controls. The incorporation of an IM separation prior to m/z measurement by MS was shown to reduce non-target ion responses from the bio-fluid matrix. PMID- 22088352 TI - Surrogate based accurate quantification of endogenous acetylcholine in murine brain by hydrophilic interaction liquid chromatography-tandem mass spectrometry. AB - Cholinergic dysfunction is known as a hallmark feature of Alzheimer's disease (AD). Measurement of endogenous acetylcholine (ACh) in specific brain regions is important in understanding the pathology of AD and in designing and evaluating novel cholinomimetic agents for the treatment of AD. Since ACh is an endogenous neurotransmitter, there is no real blank matrix available to construct standard curves. It has been a challenging task to determine ACh in complex brain matrices. To overcome these difficulties, we employed a surrogate analyte strategy using ACh-d(4) instead of ACh to generate calibration curves and Ch-d(9) as internal standard (IS). The brain samples were deproteinized by acetonitrile with IS. Analytes and IS were separated by a HILIC column with the mobile phase composed of 20 mM ammonium formate in water-acetonitrile (30:70, v/v, adjusted to pH 3.0 with formic acid) and monitored in multiple reaction monitoring (MRM) mode using a positive electrospray source. The concentrations of endogenous ACh were calculated based on the peak area ratio of the analyte to the IS using a regression equation for the corresponding surrogate standard (ACh-d(4)). The lower limit of detection was 0.2 ng/mL and linearity was maintained over the range of 10-1000 ng/mL. Compared to other currently available methods, this approach offers improved accuracy and precision for efficient analysis of ACh. The proposed method was proved successfully by evaluating the action of typical acetylcholinesterase inhibitor huperzine A in senescence accelerated mouse prone 8 (SAMP8). PMID- 22088353 TI - Extractive ethoxycarbonylation in high-temperature gas chromatography-mass spectrometry based analysis of serum estrogens. AB - A comprehensive gas chromatography-mass spectrometry (GC-MS)-based profiling was developed as a practical assay for quantification of 18 endogenous estrogens in serum samples. The present GC-MS method was conducted with the two-phase extractive ethoxycarbonlyation (EOC) of the phenolic hydroxy groups of estrogen with ethyl chlorformate combined with the non-polar n-hexane extraction. The subsequent perfluoroacylation of aliphatic hydroxy groups with pentafluoropropionyl anhydride (PFPA) was conducted. The serum samples were separated through a high temperature GC column (MXT-1) within an 8-min run and analyzed in selected-ion monitoring mode with good chromatographic properties for 18 estrogens as their EOC-PFP derivatives. The limit of quantification (LOQ) was 0.025-0.10 ng/mL for most estrogens analyzed except for E3 and 2-OH-E3 (0.5 ng/mL each). The devised method was found to be linear over a 10(3)-fold concentration range with a correlation coefficient (r(2)>0.992), whereas the precision (% CV) and accuracy (% bias) ranged from 3.1 to 16.3% and from 93.5 to 111.1%, respectively. Decreased 2-methoxy-17beta-estradiol levels were confirmed in patients with preeclampsia than healthy pregnant women. This technique can be used for a clinical diagnosis as well as understanding the pathogenesis in estrogen-related disorders. PMID- 22088354 TI - Lewisite metabolites detection in urine by liquid chromatography-tandem mass spectrometry. AB - A sensitive and simple method for the quantification and for the detection of 2 chlorovinylarsonous (CVAA) and 2-chlorovinylarsonic (CVAOA) acids was developed. CVAA and CVOA are important biological markers in human and rat urine specific to lewisite (chlorovinylarsonous chloride compounds) exposure. The developed assay was based on the use of solid-phase extraction (SPE) followed by liquid chromatography coupled to electrospray ionization (negative ion-mode) low-energy collision dissociation-tandem mass spectrometry (ESI-CID-MS/MS). The method demonstrated linearity over at least three orders of magnitude and had a detection limit (LOD) of 0.5 ng/ml for CVAA and 3 ng/ml for CVAOA. The relative standard deviations for the quality control samples ranged from 6 to 11%. Application of this procedure was demonstrated in the lewisite animals exposure model. Rats were exposed intravenously by no lethal doses of lewisite and markers levels in urine samples were analyzed for 21 days post-exposure. PMID- 22088355 TI - Selection of the derivatization reagent--the case of human blood cholesterol, its precursors and phytosterols GC-MS analyses. AB - Phytosterols (PS; beta-sitosterol and campesterol) and cholesterol precursors (CP; desmosterol and lathosterol) have been suggested as important biochemical markers of cholesterol intestinal absorption and liver biosynthesis, respectively. Given that these compounds appear in human blood in low amounts, sensitive and accurate methodology is required, such as gas chromatography-mass spectrometry (GC-MS) the most frequently used. One of the most critical factors of the GC analytical determination is the step of derivatization. Thus, the main objective of the present study was compare and select the better (one out of three) silylation mixtures as follows: N-methyl-N-(tert butyldimethylsilyl)trifluoroacetamide/ammonium iodide (MTBSTFA:NH(4)I), N-O-bis (trimethylsilyl) trifluoroacetamide/trimethylchlorosilane (BSTFA:TMCS), and N methyl-N-(trimethylsilyl)-trifluoroacetamide/1,4 dithioerythritol/trimethyliodosilane (MSTFA:DTE:TMIS). The results of this study are discussed and accompanied by a brief review on the importance and principles of derivatization process, specifically in silylation reactions in GC-MS sterols analyses. Furthermore, a scrutiny of some published results is presented, along with additional information about mass spectral data of these potentially useful compounds. Interestingly, the results of the study showed that from the three validated methodologies, the selected one, based on the best relation specificity/sensibility, is MSTFA:DTE:TMIS. With this silylation procedure for simultaneous determination of PS and CP in human serum by GC-MS in selected ion monitoring (SIM) mode, good linearity (r(2)>=0.931), precision (repeatability ranging from 0.92 to 3.91 CV and intermediate precision ranging from 5.12 to 6.33) and recoveries (>=93.6%) were obtained. Thus, it proved to be a helpful methodology in the quantification of predominant serum cholesterol origin in each patient. PMID- 22088356 TI - [Efficacy of intravitreal injections of ranibizumab compared to visudyne phototherapy in myopic choroidal neovascularization associated with high myopia]. AB - INTRODUCTION: Myopic choroidal neovascularization (CNV) is the first cause of CNV in young patients. The aim of this study was to compare the efficacy of intravitreal injections (IVT) of ranibizumab with photodynamic therapy (PDT) in this indication. PATIENTS AND METHODS: Retrospective comparative study analyzing the visual acuity (VA) outcomes of CNV myopic patients treated with either IVT or PDT. RESULTS: Twenty-seven eyes of 25 patients were treated with PDT (group 1) and 18 eyes of 17 patients were treated with IVT of ranibizumab (group 2). Demographic data were similar in the two groups. The median initial VA was 20/80 for group 1 and 20/160 for group 2 (P=0.37). At 1 year, the median VA was 20/80 for group 1 (P=0.32) and 20/63 for group 2 (P=0.04). A significant improvement in VA was observed in 23.1% and in 27.3% of cases in groups 1 and 2, respectively (P=0.53). A significant VA worsening was observed in 34.6% of cases in group 1 and in 9.1% of cases in group 2 (P=0.21). CONCLUSION: IVT of ranibizumab compared to PDT treatment showed greater efficacy in this study. PMID- 22088357 TI - Rapid and high resolution genotyping of all Escherichia coli serotypes using 10 genomic repeat-containing loci. AB - Our laboratory has previously published two multiple-locus variable-number tandem repeats analysis (MLVA) methods for rapid genotyping of Escherichia coli (E. coli), which are now in routine use for surveillance and outbreak detection. The first assay developed was specific for E. coli O157:H7; however this assay was not suitable for genotyping other E. coli serotypes. A new generic MLVA-assay was then developed with the capability of genotyping all E. coli serotypes. This generic E. coli MLVA (GECM7) was based on polymorphism in seven variable number of tandem repeats (VNTR) loci. GECM7 worked well with the majority of E. coli serotypes; however we wanted to increase the resolution for this method based in part of comparison with PFGE typing of E. coli O26:H11, where PFGE appeared to display higher resolution. The GECM7 method was improved by adding three new repeat-loci to a total of ten (GECM10), and a considerable increase in resolution was observed (from 296 to 507 genotypes on the same set of strains). PMID- 22088358 TI - Inactivation of Alternaria brassicicola spores by supercritical carbon dioxide with ethanol entrainer. AB - Supercritical carbon dioxide (SC-CO(2)) was used to inactivate fungal spores of Alternaria brassicicola. The inactivation conditions were optimized using response surface methodology (RSM). When the SC-CO(2)-entrainer (ethanol) system was applied to fungal spores, the treatment time required for the complete inactivation of fungal spores was substantially reduced. PMID- 22088359 TI - Comparative evaluation of surgical outcome after removal of impacted mandibular third molars using a Piezotome or a conventional handpiece: a prospective study. AB - Our aim was to compare the use of a conventional rotary handpiece and a Piezosurgical unit for extraction of lower third molars. We studied 40 patients, who were allocated alternately to have the third molar removed with either the handpiece or the Piezosurgical unit. Pain, trismus, and oedema were evaluated at baseline and then postoperatively, together with paraesthesiae, on postoperative days 1, 3, 5, 7, and 15. Damage to surrounding tissue was checked on the same day whereas dry socket was evaluated from postoperative day 3 onwards. More patients complained of pain in the conventional group, they also required more analgesics, and they developed trismus more often than in the Piezosurgery group. There was also significantly more postoperative swelling in the conventional group. Patients were also evaluated using the subjective Postoperative Symptom Severity (PoSSe) scale. Our results suggest that apart from some inherent limitations with the Piezotome, it is a valuable alternative for extraction of third molars. PMID- 22088360 TI - Clinical and radiological observation in a surgical series of 36 cases of fibrous dysplasia of the skull. AB - OBJECTIVES: To describe the clinical and radiological findings in a consecutive series of patients diagnosed with fibrous dysplasia of the skull. PATIENTS AND METHODS: A retrospective analysis of collected data for 36 patients with histopathologically confirmed fibrous dysplasia involving the skull is presented. The demographic data, clinical presentation, radiographic characteristics, and the management of these patients were reviewed. RESULTS: All 36 patients in this review were diagnosed with fibrous dysplasia involving at least part of the skull. In this study, the most commonly involved area of the skull was the frontal bone (52.78% of patients). The next most common area of skull was the temporal bone (30.56% of patients), followed by the sphenoid bone (25% of patients), the parietal bone (19.44% of patients), and orbital bone (13.89% of patients). The principal clinical presentation included headache, local lump, exophthalmos, visual disorder, cranial nerve paralysis, and facial malformation. These patients were treated by surgical treatment, and several of our patients underwent various degrees of reconstruction to optimize function. CONCLUSIONS: Effective surgical treatment may improve the short-term outcome in these patients, and a "tailored" surgical approach is necessary. PMID- 22088361 TI - Patients with migraine correctly estimate the visual verticality. AB - OBJECTIVE: We wanted to study otolith function by measuring the static subjective visual vertical (SVV) in migraine patients and in controls with and without kinetosis (motion sickness). METHODS AND MATERIAL: Forty-seven patients with moderately severe migraine and 96 healthy controls were enrolled. Using a questionnaire, persons with kinetosis were identified. The SVV test was performed in a totally dark room. Subjects wore a stiffneck to stabilize the head in an erect position. They were required to adjust an infrared line to the gravitational vertical with a hand-held infrared remote controlled potentiometer. RESULTS: The deviation of SVV in the group of migraine patients was not significantly different from that of controls, regardless of whether an aura was associated. SVV was not significantly influenced by the presence of dizziness/non specific vertigo or kinetosis. CONCLUSION: Patients with moderately severe migraine under prophylactic medication correctly estimate the visual verticality in the headache-free period. It is suggested that a deviation of SVV in a headache-free migraine patient may not be attributed to his migraine disorder as such regardless whether kinetosis is associated. PMID- 22088362 TI - Preliminary findings of the effects of autonomic dysfunction on functional outcome after acute ischemic stroke. AB - BACKGROUND AND PURPOSE: Impaired autonomic function is common in the acute poststroke phase but little is known about its effects on functional outcome after acute ischemic stroke. This study sought to investigate the impact of autonomic dysfunction by Ewing's classification on functional outcome 2 months after acute ischemic stroke. METHODS: 34 consecutive acute ischemic stroke patients within 7 days after onset were enrolled. On admission, autonomic function was assessed by Ewing's battery tests. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS), autonomy in activities of daily living by the Barthel Index (BI), and global disability by the modified Rankin Scale (mRS). BI and mRS were also evaluated 2 months after ischemic stroke onset. RESULTS: On admission, eight patients were diagnosed as minor autonomic dysfunction and 26 patients as relatively severe autonomic dysfunction. The prevalence of relatively severe autonomic dysfunction in ischemic stroke patients was 76.5%. There were no significant differences in baseline characteristics between the minor and severe autonomic dysfunction groups. 2 months after stroke onset, the mean BI score of patients with minor autonomic dysfunction and severe autonomic dysfunction increased from 76.3+/-15.3 on admission to 95.0+/-7.1, 66.5+/-15.2 on admission to 74.8+/-15.9 respectively. The mean BI score after 2 month stroke onset and the change in BI from admission to 2-month outcome (delta BI) in patients with severe autonomic dysfunction were lower than those in patients with minor autonomic dysfunction (all P<0.05). CONCLUSIONS: Autonomic dysfunction occurs in acute stroke patients. Relatively severe autonomic dysfunction is related to an unfavorable functional outcome in patients with acute ischemic stroke. PMID- 22088363 TI - A grid-like hemi-field defect following a lacunar infarct in the lateral geniculate nucleus. PMID- 22088364 TI - Open vertebroplasty in the treatment of spinal metastatic disease. AB - BACKGROUND: Metastatic spine tumors can cause vertebral body (VB) osteolysis, microfractures, and/or compression fractures, and requires restabilization of the VB. Curative or curettage surgery, such as vertebrectomy and reconstruction, is currently the main method of treatment. In certain situations however, such as a patient's poor condition, multi-level involvement, or a limited life expiration, major surgery is not recommended. OBJECTIVE: To evaluate a new method of open vertebroplasty (OVP) in the treatment of VB metastasis and to investigate the indications for, limitations of, and the result of this new procedure. METHODS: Between May 2007 and May 2010, the authors treated 18 patients with VB metastasis disease by OVP. Patients consisted of 12 men and 6 women with a mean age of 53 years. All patients suffered severe back pain preoperatively (mean VAS score of 6.82). Spinal cord compression resulted in eight and isolated radicular compression occurred in three of the 18 patients. In these 18 patients, 28 vertebral levels were treated: three levels in 3 patients; two levels in 4 patients; and one level in the remaining 11 patients. OVP was used accompanied by vertebral fixation or medullary compression. RESULTS: The mean duration of the OVP procedure was 37 min. Blood loss ranged from 50 to 150 ml. In all patients, pain improved within seven days after the intervention, and the mean VAS score decreased to 2.31. Patients who suffered from neurological dysfunction preoperatively improved in Frankel degree (the result of spinal cord decompression). Most patients reached an excellent score, according to the Modified MacNab Criteria. Postoperative radiography revealed cement leaks into pulmonary veins in one case. After OVP or PVP, all patients underwent radiotherapy or chemotherapy. CONCLUSIONS: OVP has a comprehensive application in metastasis spinal column disease, being easily performed and accompanied by few complications. Importantly, this procedure allows decompression of the spinal cord and consolidation of the VB, thus stabilizing the vertebral column. Results from the clinic demonstrate that patients experience pain relief and neural function recovery following the OVP procedure. PMID- 22088365 TI - Association of total body and visceral fat mass with iron deficiency in preadolescents: the Healthy Growth Study. AB - The aim of the present study was to examine the associations of obesity, percentage body fat and visceral fat mass with body Fe status in a representative sample of 1493 schoolchildren aged 9-13 years. Anthropometric, body composition, biochemical, clinical (Tanner stage, age of menarche) and dietary intake data were collected. Fe deficiency (ID) was defined as transferrin saturation (TS) < 16 %; and Fe-deficiency anaemia (IDA) as ID with Hb < 120 g/l. Obese boys and girls and those in the highest quartiles of percentage body fat mass had significantly higher levels of serum ferritin (P <= 0.05) compared to their normal-weight peers and those in the corresponding lowest quartiles. Similarly, obese boys and girls and those in the highest quartiles of percentage body fat and visceral fat mass had significantly lower levels of TS (P <= 0.05) compared to normal-weight children and those in the corresponding lowest quartiles. The prevalence of ID and IDA was significantly higher in boys and girls in the highest quartiles of percentage body fat than in peers in the lowest quartile. Higher quartiles of percentage body fat and visceral fat mass were the main significant predictors of ID in boys, after controlling for other important confounders, with OR of 2.48 (95 % CI, 1.26, 4.88) and 2.12 (95 % CI, 1.07, 4.19), respectively. Similar significant associations were observed for girls. In conclusion, percentage body fat and visceral fat mass were positively associated with ID in both sexes of preadolescents. These associations might be attributed to the chronic inflammation induced by excess adiposity. PMID- 22088367 TI - [Molecular pathology of multifocal prostate cancer and its clinical application]. PMID- 22088366 TI - Creativity and bipolar disorder: touched by fire or burning with questions? AB - Substantial literature has linked bipolar disorder with creative accomplishment. Much of the thinking in this area has been inspired by biographical accounts of poets, musicians, and other highly accomplished groups, which frequently document signs of bipolar disorder in these samples. A smaller literature has examined quantitative measures of creativity among people with bipolar disorder or at risk for the disorder. In this paper, we provide a critical review of such evidence. We then consider putative mechanisms related to the link of bipolar disorder with creativity, by drawing on literature outside of bipolar disorder on personality, motivational, and affective predictors of creativity. Because so little research has directly evaluated whether these factors could help explain the elevations of creativity in bipolar disorder, we conclude with an agenda for future research on the theoretically and clinically compelling topic of creativity in bipolar disorder. PMID- 22088368 TI - [Clinical and pathologic features of renal mucinous tubular and spindle cell carcinoma]. AB - OBJECTIVE: To investigate the clinical and pathological features of the mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney. METHODS: Seven cases of MTSCC were analyzed by gross examination and light microscopy. Immunostaining was performed to detect the expression of CD10, CK7, CK18, CK19, Villin, EMA, P504S and vimentin. The literature on this tumor was reviewed to discuss the histological features of MTSCC and its clinical behavior. RESULTS: Three of 7 cases were male and the other 4 were female. The mean age of the patients was 48.2 years old, with a range from 39 to 61 years. All the patients presented no symptom and their tumors were found by health examination. Tumors averaged 5.5 cm in greatest dimension (range from 4.0 cm to 9.0 cm). The tumors were well circumscribed without capsules, and the cut surfaces were solid and soft with white-tan color. By light microscopy, tumors were composed of tightly packed, small, elongated tubules with transitions to spindle cell components. Five cases had mucinous stroma. Clear cell clusters, focal sarcomatoid differentiation, papillations and foamy macrophages were seen in several cases. Immunohistochemically, all 7 cases showed positive for CK7, five of 5 cases positive for EMA, CK18 and P504S, four of 5 cases positive for CK19, but heterogeneous for CD10, villin and vimentin expression. No evidence of local recurrence or distant metastases was identified in the 5 patients with follow-up information. CONCLUSIONS: The mucinous tubular and spindle cell carcinoma is a low-grade and polymorphic neoplasm. The morphology of these tumors may not be uniform with a wide histological spectrum. The tumors can be tubular predominant or spindle cells predominant with scant to abundant mucinous stroma, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, necrosis and sarcomatoid differentiation. Immunohistochemically, MTSCC can express the markers from the proximal convoluted tubules to collecting tubules. PMID- 22088369 TI - [Mucinous tubular and spindle cell carcinoma of kidney: a clinicopathological study]. AB - OBJECTIVE: To investigate the clinicopathological features, histogenesis and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC). METHODS: Five MTSCCs were studied with histochemical, immunohistochemical staining, electron microscopy, and review of the related literatures. RESULTS: Four cases of MTSCC were females and one was male. Three patients presented with flank discomfort and two were incidentally found with health examination. In gross examination, the tumors were circumscribed. The cut surface was solid, gray-white, yellow or red. Necrosis was present in one case of high-grade MTSCC. Microscopically, low-grade MTSCC was mainly consisted of tubular, spindle cell and mucinous stroma with relatively bland morphology, and mitoses were rare. While in the high-grade area of one case, the cells were spindle or polymorphic with severe atypia and high mitotic activity, without mucinous stroma and tubular structure. Mucin was positive for Alcian blue. The neoplastic cells were positive for vimentin (5/5), CKpan (5/5), CK7 (5/5), CK19 (5/5), 34betaE12 (1/5), EMA (5/5), E-cadherin (3/5), CD10 (1/5), P504S (5/5), and CAM5.2 (5/5). The Ki-67 index was low (< or = 5%) in the low-grade component, while it was high (15%) in the high-grade component. Ultrastructural study showed short microvilli along glandular lumens. The nuclear membrane was focally invaginated. Four cases were followed up for 3 to 52 months, and recurrence and metastasis were not found. CONCLUSIONS: MTSCC occurs predominantly in females and it is a rare kidney neoplasm. Most of MTSCCs are low grade and the prognosis is relatively good. However, the patients of high-grade MTSCC should be closely followed up. PMID- 22088370 TI - [Correlation of 53BP1 gene mutation with prostatic adenocarcinoma]. AB - OBJECTIVE: To study the incidence of 53BP1 gene mutations in prostatic adenocarcinoma and benign prostatic hypertrophy, and to analyze the relationship between 53BP1 mutations and prostatic adenocarcinoma. METHODS: Genomic DNA extraction, PCR amplification and gene sequencing were used to detect the occurrence of 53BP1 gene mutations in 50 cases of prostatic adenocarcinoma. Ten cases of benign prostatic hypertrophy were included as controls. RESULTS: Amongst the 50 cases of prostatic adenocarcinoma studied, 15 showed genetic alterations of 53BP1, including 4 cases with single nucleotide polymorphism. The mutation rate was 24.0% (12/50). Seven of the 53BP1 mutations detected represented missense mutations and none of them were situated in functionally important domains. The other 4 were synonymous mutations, in which c. 4760G > T was situated in Tudor domain. There was no obvious correlation between 53BP1 gene mutations and the various clinicopathologic parameters of prostate adenocarcinoma (P>0.05). CONCLUSION: Certain percentage of prostatic adenocarcinoma harbors 53BP1 mutations which may be involved in the carcinogenesis. PMID- 22088371 TI - [Relationship between miR-218 and CDK6 expression and their biological impact on glioma cell proliferation and apoptosis]. AB - OBJECTIVES: To investigate the relationship between the expression of miR-218 and CDK6 in glioma cells, and their biological impacts on the tumor cell proliferation and apoptosis. METHODS: Expression levels of miR-218 as well as CDK6 and Ki-67 proteins were analyzed in 60 cases of gliomas with various grades and 10 control brain tissue samples by tissue microarray, locked oligonucleotide probe in situ hybridization and immunohistochemistry. Glioblastoma multiform cell line (U87MG) was transfected with miR-218 mimics (mimics group) and a control sequence (control group), followed by qRT-PCR detection of miR-218 and immunocytochemical stain of CDK6 and Ki-67, respectively. Single cell gel electrophoresis was used to detect the presence of apoptotic cell. RESULTS: The miR-218 labeling indexes (LI) were statistically different (P<0.05) among all groups including control (22.45 +/- 0.59) and various glioma groups (grades I - II 4.00 +/- 1.07, grade III 1.87 +/- 1.06 and grade IV 0.94 +/- 0.78, respectively). The CDK6 LI of the four groups was 7.25 +/- 1.20, 16.71 +/- 0.80, 24.43 +/- 0.62 and 32.05 +/- 0.43, respectively. Significant differences existed between the control group and the glioma groups, and between grade IV and grades I - II glioma groups (P<0.01). Ki-67 positive cell densities of the above four groups (0.00 +/- 0.00, 9.30 +/- 3.48, 31.15 +/- 9.44 and 60.15 +/- 13.60) were significantly different from one and another (P<0.01). The expression of miR-218 negatively correlated with CDK-6 LI (r = -0.480, P<0. 01) and Ki-67 positive cell density (r = - 0.534, P<0.01), while the latter two positively correlated with each other (r = 0.530, P<0.01). U87MG transfection experiment showed that the miR 218 level of the mimics group was significantly higher than that of the control group (P<0.01). CDK6 and Ki-67 LI of the mimics group (14.74 +/- 1.19 and 30.88 +/- 3.31) were significantly lower than those of the control group (79.06 +/- 2.07 and 64.94 +/- 3.96, P<0.01), whilst its apoptotic index (AI) (68.44 +/- 7.05) was significantly higher than that of the control group (13.04 +/- 0.97, P<0.01). CONCLUSIONS: The expression level of miR-218 is an important reference indicator for the assessment of the grade of gliomas. An aberrant decrease of its expression may lead to an increase of the CDK6 expression and proliferative activity of giloma cells. Introducing exogenous miR-218 may effectively down regulate the CDK6 expression, inhibit cell proliferation and induce apoptosis of malignant giloma cells. These findings imply that miR-218 may serve as a therapeutic agent against malignant glioma. PMID- 22088372 TI - [Pulmonary lymphomatoid granulomatosis: an immunohistochemical and gene rearrangement study]. AB - OBJECTIVE: To study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis. METHODS: Nine cases of pulmonary lymphomatoid granulomatosis, included 5 cases of open lung biopsy, 3 cases of lobectomy specimen and 1 case of autopsy, were retrospectively analyzed by immunohistochemistry, in-situ hybridization for Epstein-Barr virus-encoded RNA, immunoglobulin and T-cell receptor gene rearrangement studies. RESULTS: The age of patients ranged from 3 to 59 years. The male-to-female ratio was 3: 6. Histologically, all cases showed lymphocytic infiltration surrounding the blood vessels and in the perivascular areas. Most of these lymphoid cells expressed T cell marker CD3. There were also variable numbers of CD20-positive B cells. The staining for CD56 was negative. According to the WHO classification, there were 4 cases of grade I , 1 case of grade II and 4 cases of grade III lesions. Six cases had gene rearrangement studies performed and 3 of them demonstrated clonal immunoglobulin gene rearrangement (including 1 of the grade II and 2 of the grade III lesions). No T-cell receptor gene rearrangement was detected. CONCLUSIONS: Pulmonary lymphomatoid granulomatosis may represent a heterogeneous group of lymphoproliferative disorders. Some of the cases show B-cell immunophenotype and clonal immunoglobulin gene rearrangement, especially the grade II and grade lesions. They are likely of lymphomatous nature. PMID- 22088373 TI - [Comparison of histopathologic changes and expression of biomarkers in breast carcinoma before and after neoadjuvant chemotherapy]. AB - OBJECTIVE: To investigate the relationship between the pathologic responses and histologic type, grade, the expression of ER, PR and HER2 and their changes in breast carcinoma before and after neoadjuvant chemotherapy (NAC). METHODS: Two hundred and nine cases of breast cancer with NAC were analyzed and clinical, pathologic data were evaluated based on the Miller and Payne ( MP) grading system. The expression of ER, PR and HER2 in the cancers before and after NAC were detected by immunohistochemistry (MaxVision method). SPSS 15.0 software was used to conduct statistical analysis. RESULTS: (1) Pathologic responses to the NAC were graded as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases); (2) The expression of ER in core needle biopsy had related negatively to the pathologic response (chi2 = 33.083, P = 0.001). However, the histologic type, grade, ER and PR status, and HER2 expression in surgically-removed specimens had not related to the pathologic response (P>0.05); (3) After NAC, the pathologic type and grade changed in 6. 8% (9/132) and 34.9% (30/86) of the cases, and the rates of changes in the expression of ER, PR and HER2 were 42.4% (75/177), 55.4% (98/177) and 26.6% (46/173) , respectively. Only the expression of HER2 had significant difference between before and after neoadjuvant chemotherapy (P = 0.049). The changes in other data had no relationship with the pathologic response (P>0.05). CONCLUSIONS: Analysis of core needle biopsy can provide important information to predict the pathologic responses to the NAC. The pathologic appearance, grade, ER, PR and HER2 in breast carcinoma may change after NAC. It is necessary to examine the histologic type, grade and the expression of ER, PR and HER2 after NAC once more. PMID- 22088374 TI - [Invasive carcinoma arising in breast microglandular adenosis: a clinicopathologic study of three cases and review of the literature]. AB - OBJECTIVE: To study the clinicopathologic features, immunophenotypes and differential diagnoses of invasive carcinoma arising in breast microglandular adenosis (MGACA). METHODS: Clinical and pathologic findings of 3 cases of MGACA were analyzed by histomorphology and immunohistochemical staining of CK7, S-100 protein, ER, PR, HER2, SMA, MSA, p63 and PAS. Literatures were reviewed. RESULTS: (1) Histologically, 3 tumors all showed a spectrum of glandular proliferations ranging from microglandular adenosis (MGA) to atypical microglandular adenosis (AMGA) to in situ carcinoma (DCIS) to invasive carcinoma. The invasive carcinoma component was ductal in case 1, and matrix-producing in case 2 and case 3. (2) All epithelial cells in MGA, AMGA, DCIS and MGACA were positive for CK7 and S-100 protein, but were negative for ER and HER2. PR was negative in case 1 and case 2 but was low positive in case 3. Myoepithelial cell differentiation was not demonstrated in MGA, AMGA, DCIS and MGACA by immunohistochemical staining for SMA, MSA or p63. PAS staining showed the presence of basement membrane in MGA, AMGA and DCIS, except MGACA. CONCLUSIONS: MGACA is an extremely rare tumor of the breast and has distinct morphological and immunohistochemical features. Further studies are needed to evaluate the clinical behavior of this rare neoplasm. PMID- 22088375 TI - [Establishment of experimental angiogenic models with applications of quantitative digital image analysis]. AB - OBJECTIVE: To establish experimental models for tumor neovascularization and to apply quantitative digital imaging analysis in the study. METHODS: An endothelial tube formation model was established by human umbilical vein endothelial cells (HUVECs). A vasculogenic mimicry model was established by SGC-7901 gastric cancer cell line. Fertilized eggs were used to establish a chorioallantoic membrane angiogenesis model. Using gene transfection experiment, IRX1 tumor suppressor gene was chosen as a therapeutic target. Image Pro Plus (IPP) analysis software was used for digital vascular images analysis with parameters including points, lines, angles and integral absorbance (IA) for the tubular formation or vasculogenic mimicry. RESULTS: Digital image analysis by IPP showed that HUVEC tubular formation was significantly inhibited in IRX1 transfectant, compared with controls. The tubular numbers in three groups were 12.80 +/- 3.83, 29.00 +/- 5.34 and 28.20 +/- 4.32 (P<0.01). The connection points of tubules in three groups were 13.20 +/- 2.59, 25.00 +/- 2.24 and 24.60 +/- 3.21 (P<0.01). The tubular lengths of three groups were (821.5 +/- 12.5), (930.9 +/- 13.5) and (948.4 +/- 18.1) microm (P=0.022). The IA values of PAS stain in three groups were 3606 +/- 363, 14 200 +/- 1251 and 15 043 +/- 1220 (P<0.01). In chick chorioallantoic membrane model, the angular numbers of tubules in three groups were 6.41 +/- 2.60, 10.27 +/- 2.65 and 9.18 +/- 1.99 (P<0.01). CONCLUSIONS: The endothelial tube formation model, vasculogenic mimicry model and chorioallantoic membrane angiogenesis model are useful for gene therapy and drug screening with targeting neoplastic vascularization. Professional image analysis software may greatly facilitate the quantitative analysis of tumor neovascularization. PMID- 22088376 TI - [Intracranial clear cell meningioma: a clinicopathologic analysis]. PMID- 22088377 TI - [Compare three methods to detect the Pneumocystis carinii in the bronchoalveolar wash sample of AIDS patients]. PMID- 22088378 TI - [Detection of the expression of HER2 using CdTe/ZnSe core/shell quantum dots as fluorescence probe in breast cancer cells]. PMID- 22088379 TI - [Thyroid metastatic renal clear cell carcinoma: report of a case]. PMID- 22088380 TI - [Glomerulocystic kidney disease: report of a case]. PMID- 22088381 TI - [Fibrous hamartoma of infancy: report of a case]. PMID- 22088382 TI - [Thyroid paraganglioma: report of a case]. PMID- 22088383 TI - [Hepatic lymphoepithelioma-like cholangiocarcinoma: report of a case]. PMID- 22088384 TI - [Intracranial primary malignant melanoma: report of a case]. PMID- 22088385 TI - [Research advance in tumors associated with microphthalmia-associated transcription factor gene family]. PMID- 22088386 TI - [Update of secretagogin]. PMID- 22088387 TI - Assessment of acute cholangitis by MR imaging. AB - PURPOSE: The purpose of this study is to assess the common MRI findings of acute cholangitis compared with those of non-acute cholangitis. MATERIALS AND METHODS: During a 31-month period, we performed MRCP and contrast-enhanced MRI on 173 patients with biliary abnormalities including duct dilatation or stricture. The causes of the biliary abnormalities included biliary stone disease (n=85), cholangiocarcinoma (n=47), periampullary cancer (n=20), GB cancer (n=4), and others (n=17). Among 173 patients, 66 consecutive patients were confirmed with acute cholangitis diagnosed according to the Tokyo guideline, and 107 patients were confirmed as having non-acute cholangitis. Two radiologists retrospectively and independently accessed the MR findings, including the cause of biliary abnormality, increased periductal signal intensity on T2-weighted images, the transient periductal signal difference, and the presence of abscess, thrombosis, and ragged duct. They also measured the dilated duct and the thickened wall. The Student t-test and the Pearson chi-square were used. The kappa statistics were used to determine interobserver agreement. Logistic regression was used to identify the MR findings that predicted acute cholangitis. RESULTS: MRI correctly accessed the cause of biliary abnormality in 163 patients (94%). The statistically common findings for acute cholangitis were as follows: increased periductal signal intensity on T2-weighted imaging (n=26, 39%, p<0.05); transient periductal signal difference (n=31, 47%, p<0.05); abscess (n=18, 27%, p<0.05); thrombosis (n=12, 18%, p<0.05); and ragged duct (n=11, 17%, p<0.05). Interobserver agreement was good to excellent for each finding (kappa=0.74-0.97). The wall thickness showed a statistically significant difference between the acute cholangitis and the non-acute cholangitis group (2.65 mm:2.32 mm, p<0.05), however, there was no significant difference in duct dilatation in the two groups. The periductal transient attenuation difference was an independent predictor of acute cholangitis (Exp (B)=6.389, p=0.018). CONCLUSION: MRI accurately assesses the cause of biliary abnormality in patients with cholangitis. Using statistically common MR findings for acute cholangitis, MR imaging is very successful in predicting acute cholangitis. PMID- 22088388 TI - An accurate multislice method for low-energy transmission electron microscopy. AB - The conventional multislice method (CMS), originally proposed by Cowley and Moodie (1957), is an important algorithm for image and electron diffraction calculations in transmission electron microscopy. Nevertheless, this method is based on the so-called high-energy approximation, which neglects the second differential term ?(2)phi(r)/?z(2) to greatly simplify the calculation without severe loss of accuracy. In the current study, we show that for low-energy transmission electron microscopy (LE-TEM) (<100 kV), the high-energy approximation error becomes large and the accurate multislice method, proposed by Chen and Van Dyck (1997), can be used as an alternative method to obtain more accurate calculations. The accurate multislice method, called the revised real space method (RRS) in this paper, can be realized by treating the propagation and scattering as an entirety in real space. A detailed comparison of the numerical results of the RRS and CMS at different accelerating voltages, Debye-Waller factors, and beam tilts is performed. Results show that for image and diffraction simulations in LE-TEM, CMS is no longer sufficiently accurate and the RRS procedure can be used as an alternative method with reasonable computing time. PMID- 22088389 TI - Tergal glands in termite soldiers of the subfamily Syntermitinae (Isoptera: Termitidae). AB - The subfamily Syntermitinae comprises 14 genera of termites that are exclusively neotropical. The present study reports morphological data about mandibulate nasute soldiers from termite species belonging to three different genera within this subfamily. We describe tergal glands that were present under all tergites of soldiers of the following species: Cornitermes cumulans, Procornitermes araujoi, Syntermes nanus, and Syntermes wheeleri. The tergal glands were composed of class 2 and class 3 cells. Class 2 cells never reached the cuticle and were located below a flat layer of epidermal cells. Class 3 cells, composed of secretory cells and canal cells, were sporadic, whereas class 2 secretory cells were abundant. Secretory cells of class 3 were narrow and their cytoplasms were filled with several clear, oval-shaped vesicles with limiting membranes. The ultrastructure of class 2 cells showed well-developed smooth endoplasmic reticulum, Golgi apparatus, elongated mitochondria, several electron-lucent vesicles, and electron dense granules that contain paracrystalline structures in S. nanus. Scanning electron micrographs displayed pores, campaniform sensilla and hairs in the outer cuticle of the soldier tergites. We hypothesize that soldier tergal glands may be involved in the production of defensive compounds, which occur in similar glands of certain cockroaches, or of primer pheromones, that might act in the regulation of soldier differentiation in the termite colony. To date, tergal glands have only been described in termite imagoes, and their occurrence in these soldiers of basal Syntermitinae implies a specific role in this caste that is still speculative and needs to be clarified. PMID- 22088390 TI - Autogenous grafts for condylar reconstruction in treatment of TMJ ankylosis: current concepts and considerations for the future. AB - Temporomandibular joint (TMJ) ankylosis is characterized by difficulty or inability to open the mouth due to fusion of the temporal and the mandible, resulting in facial symmetry/deformity, malocclusion and dental problems. The only treatment option for TMJ ankylosis is surgical with or without condylar reconstruction. Various autogenous grafts are available for condylar reconstruction after freeing the ankylotic mass such as costochondral, sternoclavicular, fibular, coronoid, and metatarsophalangeal. Costochondral graft is preferred by surgeons, but distraction osteogenesis is slowly gaining popularity and may ultimately become the standard procedure, providing a cost effective approach with low morbidity and excellent functional outcomes. Tissue engineering is another budding field which has shown promising results in animal studies but has not been applied to humans. To date, there is no ideal autogenous graft for condylar reconstruction that satisfies the complex anatomy and the myriad of functions of a missing condyle. PMID- 22088391 TI - Nanoscale analysis of structural synaptic plasticity. AB - Structural plasticity of dendritic spines and synapses is an essential mechanism to sustain long lasting changes in the brain with learning and experience. The use of electron microscopy over the last several decades has advanced our understanding of the magnitude and extent of structural plasticity at a nanoscale resolution. In particular, serial section electron microscopy (ssEM) provides accurate measurements of plasticity-related changes in synaptic size and density and distribution of key cellular resources such as polyribosomes, smooth endoplasmic reticulum, and synaptic vesicles. Careful attention to experimental and analytical approaches ensures correct interpretation of ultrastructural data and has begun to reveal the degree to which synapses undergo structural remodeling in response to physiological plasticity. PMID- 22088394 TI - Good things come in small packages: subcellular organization and development in bacteria. PMID- 22088392 TI - Prospect for feedback guided surgery with ultra-short pulsed laser light. AB - The controlled cutting of tissue with laser light is a natural technology to combine with automated stereotaxic surgery. A central challenge is to cut hard tissue, such as bone, without inducing damage to juxtaposed soft tissue, such as nerve and dura. We review past work that demonstrates the feasibility of such control through the use of ultrafast laser light to both cut and generate optical feedback signals via second harmonic generation and laser induced plasma spectra. PMID- 22088395 TI - Amyloidosis. PMID- 22088393 TI - Recurrent infections and immune evasion strategies of Staphylococcus aureus. AB - Staphylococcus aureus causes purulent skin and soft tissue infections (SSTIs) that frequently reoccur. Staphylococal SSTIs can lead to invasive disease and sepsis, which are among the most significant causes of infectious disease mortality in both developed and developing countries. Human or animal infections with S. aureus do not elicit protective immunity against staphylococcal diseases. Here we review what is known about the immune evasive strategies of S. aureus that enable the pathogen's escape from protective immune responses. Three secreted products are discussed in detail, staphylococcal protein A (SpA), staphylococcal binder of immunoglobulin (Sbi) and adenosine synthase A (AdsA). By forming a complex with V(H)3-type IgM on the surface of B cells, SpA functions as a superantigen to modulate antibody responses to staphylococcal infection. SpA also captures pathogen-specific antibodies by binding their Fcgamma portion. The latter activity of SpA is shared by Sbi, which also associates with complement factors 3d and factor H to promote the depletion of complement. AdsA synthesizes the immune signaling molecule adenosine, thereby dampening innate and adaptive immune responses during infection. We discuss strategies how the three secreted products of staphylococci may be exploited for the development of vaccines and therapeutics. PMID- 22088396 TI - Improving childhood nutrition in India. PMID- 22088397 TI - Moves to measure wellbeing must support a social model of health. PMID- 22088398 TI - The sentinel. PMID- 22088399 TI - A pair of ragged clauses: the health bill in the House of Lords. PMID- 22088400 TI - The painful truth: deaths and misuse of prescribed drugs. PMID- 22088401 TI - US Supreme Court to decide whether health reform law is constitutional. PMID- 22088402 TI - UK government disbands advisory group on obesity. PMID- 22088403 TI - Patients challenge trusts' decision on location of radiotherapy service. PMID- 22088404 TI - Healthcare regulator is investigated over role to protect patients. PMID- 22088405 TI - European countries cut funding for a range of activities against illicit drug use. PMID- 22088406 TI - Gynaecologist botched cosmetic vaginal operations and a termination, GMC hears. PMID- 22088407 TI - Short-term outcomes of the prone perineal approach for extra-levator abdomino perineal excision (elAPE). AB - BACKGROUND: Many studies report that low rectal cancer treated with abdomino perineal excision (APE) have higher rates of CRM involvement with associated local recurrence and worse survival when compared to low anterior resection. We present a single surgeon's short-term outcomes using the prone perineal extra levator (elAPE) approach. METHODS: Thirty-one patients between 2006 and 2010 underwent elAPE with curative intent. Data was collected prospectively recording patient tumour characteristics and histological outcome. Outcome measures included circumferential resection margins, recurrence rates, 30-day morbidity and mortality. RESULTS: Mean distance of tumour from anal verge was 3.63 +/- SD 1.52 cm. 14 patients had pre-operative chemo-radiotherapy. The involved circumferential resection margin rate was 3.2%. Median follow-up was 20 (0-45) months, with overall mortality of 13.3% and 30 day mortality of 6.6%. CONCLUSIONS: The prone position elAPE has a low circumferential resection margin involved rate and, through improved vision, reduces the risk of inadvertent tumour or specimen perforation. PMID- 22088408 TI - All words are not created equal: expectations about word length guide infant statistical learning. AB - Infants have been described as 'statistical learners' capable of extracting structure (such as words) from patterned input (such as language). Here, we investigated whether prior knowledge influences how infants track transitional probabilities in word segmentation tasks. Are infants biased by prior experience when engaging in sequential statistical learning? In a laboratory simulation of learning across time, we exposed 9- and 10-month-old infants to a list of either disyllabic or trisyllabic nonsense words, followed by a pause-free speech stream composed of a different set of disyllabic or trisyllabic nonsense words. Listening times revealed successful segmentation of words from fluent speech only when words were uniformly disyllabic or trisyllabic throughout both phases of the experiment. Hearing trisyllabic words during the pre-exposure phase derailed infants' abilities to segment speech into disyllabic words, and vice versa. We conclude that prior knowledge about word length equips infants with perceptual expectations that facilitate efficient processing of subsequent language input. PMID- 22088409 TI - The use of fetal foot length to determine stillborn gestational age in Vietnam. AB - OBJECTIVE: To assess the use of fetal foot length for predicting gestational age in stillborn fetuses in Vietnam and the ability of this measurement to differentiate early from late fetal deaths. METHODS: In a prospective case series, gestational age was determined from either certain first day of last menstrual period or early ultrasound scan. Foot length was measured, with a non elastic tape measure, from the heel to the tip of the longest toe. Agreement of observed and predicted foot length for gestational age was tested, as well as the influence of fetal characteristics. RESULTS: Accurate gestational age and foot length were available for 52 of 107 participants. Strong agreement was demonstrated between observed and predicted values of foot length across gestations (95% confidence interval, -4.7 to 4.3 weeks). Accuracy of fetal foot length in predicting gestational age was affected by growth restriction but not fetal gender, maceration, or congenital anomalies. Fetal foot length of 55 mm or greater demonstrated a sensitivity and specificity of 88% in identifying late fetal deaths. CONCLUSION: Foot length is a good differentiator of early and late fetal death, which is important for the global recording of the number of stillbirths. PMID- 22088410 TI - The legal status of emergency contraception in Latin America. AB - Timely access to emergency contraception (EC) can contribute to reducing the number of unwanted pregnancies, and ultimately, the number of unsafe abortions and maternal fatalities. In Latin America, where all countries are parties to international human rights treaties that recognize the rights to autonomy, privacy, and health, and recognize sexual and reproductive rights including the right to family planning, the legal status of EC has been discussed in the courts. This article focuses on the analysis of the principal arguments voiced in the courts: the difference between contraceptives and abortifacients, the scientific status of available research on EC, and the age at which people develop a legal right to make decisions about their personal health. The conclusion is that Latin American countries whose laws or regulations ban access to EC in the public and/or the private sector fail to fulfill their obligations under international human rights law. PMID- 22088412 TI - Management of recurrent cutaneous abscesses during therapy with infliximab. AB - BACKGROUND: Infliximab is a chimeric monoclonal antibody, belonging to the class of anti-tumor necrosis factor-alpha (TNF-alpha) agents, approved for the treatment of psoriasis and psoriatic arthritis. Drugs of this class are known to be associated with an infective risk, probably because they interfere with inflammatory and immune response at different levels. Although cutaneous Staphylococcus aureus infections seem to be more frequent than any other infection in the course of anti-TNF-alpha treatment, only a few case reports in the literature deal with this side effect, and, in particular, with its management. OBJECTIVE: Our aim was to report a case of recurrent methicillin sensitive S aureus (MSSA) cutaneous abscesses during therapy with infliximab and successful management. CASE SUMMARY: In July 2009, a 53-year-old white woman (weighing 85 kg) affected by psoriasis and psoriatic arthritis was administered infliximab (5 mg/kg IV), based upon clinical appearance and previous unsuccessful treatment with cyclosporine, methotrexate, etanercept, and adalimumab. Three days after the first 3 infusions (at weeks 0, 2, and 6) she complained about the recurrent onset of painful, erythematous, indurated, and pus-draining cutaneous nodules located on her abdomen. The swab always revealed the presence of MSSA, and antibiotic oral therapy with amoxicillin + clavulanic acid (875 + 125 mg BID for 7 days) was established, with complete resolution of the abscesses. Routine laboratory findings were in normal ranges, with the exception of an elevated erythrosedimentation rate and an increased white blood cell count (range, 13,000 15,000/mm(3)) with neutrophilia (range, 75%-80%). HIV infection was ruled out. In agreement with the infectious disease consultant, 1 day before the fourth infusion, a prophylactic antibiotic therapy with amoxicillin + clavulanic acid (875 + 125 mg BID for 5 days) was added to the therapeutic regimen. This treatment schedule was successfully repeated at each following infusion (every 8 weeks), and no recurrence of skin abscesses was observed. The patient provided signed authorization for publication of this case. CONCLUSIONS: This case report describes a woman with psoriasis and psoriatic arthritis who developed MSSA skin abscesses after each of the first 3 infliximab infusions, which did not recur for the next 6 infusions after amoxicillin + clavulanic acid was added to her regimen, pre- and 4 days postinfusion. Adequately designed, placebo-controlled, double-blind trials are needed to determine whether such prophylactic antibiotic treatment is well tolerated or effective for this common complication of therapy with anti-TNF-alpha agents, when withdrawal of the drug is not advisable, as in this case. PMID- 22088413 TI - Room-temperature-stable recombinant activated coagulation factor VII recombinant: chemical and microbiologic stability over 24 hours during continuous in vitro infusion. AB - rFVIIa-25C is a recombinant coagulation factor VIIa (rFVIIa) formulated to remain stable at room temperature (up to 25 degrees C) for up to 2 hours. The bolus injection of rFVIIa-25C has been reported to be bioequivalent to that of rFVIIa. With alternative administration by continuous infusion (50 MUg/kg/h) for surgical hemostatic coverage in hemophilia patients with inhibitors, rFVIIa has been reported to be stable. This research letter presents data from an in vitro study of the activity and chemical stability (rFVIIa content, clot activity, and degradation products), physical stability, and microbiologic stability of rFVIIa 25C administered as a continuous infusion. The findings suggest that rFVIIa-25C remained biochemically stable and aseptic during 24-hour continuous infusion in vitro at 19.3 degrees C to 20.7 degrees C, with no clinically significant changes in clot activity, solution constituents, or concentrations. PMID- 22088414 TI - Comparative pharmacokinetics and tolerability of branded etanercept (25 mg) and its biosimilar (25 mg): a randomized, open-label, single-dose, two-sequence, crossover study in healthy Korean male volunteers. AB - BACKGROUND: The biosimilar is a recombinant dimeric tumor necrosis factor receptor (TNFR) under development for the treatment of rheumatoid arthritis. OBJECTIVE: The aim of this study was to compare the pharmacokinetics and/or tolerability of branded etanercept and its biosimilar in healthy Korean men before investigating the clinical efficacy of the biosimilar in subjects. METHODS: Etanercept (reference, 25 mg) or its biosimilar (test, 25 mg) was subcutaneously injected to the periumbilical area of healthy volunteers in a randomized, open-label, single-dose, active-controlled, two-sequence, crossover study. Plasma concentrations of TNFR in serial blood samples for 480 hours after dosing were measured by ELISA. The primary outcome, pharmacokinetic characteristics, was assessed via geometric mean ratios (GMRs) of the log transformed pharmacokinetic parameters. The second outcome, tolerability, was evaluated using physical examinations, electrocardiograms, clinical laboratory tests, vital sign measurements, and adverse events (AEs) by unmasked investigators. RESULTS: Twenty-three men of mean age (%CV) 25.8 years (17.1%) and weight 70.5 kg (12.8%) were administered study medication. Four subjects dropped out after the first period; their data were included in the analysis. Both test and reference drugs were absorbed with a median T(max) of 72 (range, 36-144) hours and eliminated with mean (%CV) t(1/2) of 92.7 (20.9%) and 87.4 (16.6%) hours, respectively. The GMRs (90% CIs) of the test to reference drug for C(max), AUC(0-t), and AUC(0-infinity) were 0.99 (0.83-1.17), 0.95 (0.79-1.13), and 0.95 (0.80-1.13), respectively. Eleven of 21 (52.4%) and 8 of 21 (38.1%) subjects administered the test and reference drugs reported 22 and 21 AEs, respectively. Common AEs were headache (14.3%), throat irritation (8.5%), and epistaxis (9.5%). Three serious AEs related to a traffic accident (back, neck, and musculoskeletal pain) were reported in a test drug-treated subject. CONCLUSIONS: In this select group of Korean healthy male volunteers, the reference drug and the test biosimilar met the standard criteria for assuming bioequivalence as defined by Korean regulatory authorities. Because the reference drug is a biological product, further trials for assessment of its efficacy are still required by Korean authorities. World Health Organization International Clinical Trials Registry Platform identifier: KCT0000118. PMID- 22088415 TI - Letter to the editor. PMID- 22088416 TI - Patterns of therapy switching, augmentation, and discontinuation after initiation of treatment with select medications in patients with osteoarthritis. AB - BACKGROUND: Osteoarthritis (OA) is a debilitating condition characterized by chronic pain. Several pain medications are recommended, and patients frequently alternate among these medications. OBJECTIVES: The purpose of this study was to examine the use of pain medications in clinical practice with respect to recommended guidelines. This objective was accomplished by evaluating patterns of switching, augmentation, and discontinuation after treatment initiation with select medications in patients with OA. METHODS: The LifeLink Health Plan Claims Database was used to select patients with OA (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 715.XX) who were newly prescribed (index event) nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase (COX)-2 inhibitors, acetaminophen, tramadol, weak opioids, and strong opioids. Descriptive statistics, Kaplan-Meier analyses, and the COX proportional hazards model were used to assess therapy switching, augmentation, and discontinuation during the 12-month postindex period. Patterns of intraarticular injections and joint replacement surgeries among the cohorts were also evaluated. RESULTS: Substantial proportions of OA patients switched, augmented, or discontinued therapy during the postindex period. Rates of therapy switching, augmentation, and discontinuation, respectively, were significantly different (all P < 0.0001 for overall effects using log-rank tests) across the evaluated medication cohorts: NSAIDs, 22.3%, 6.7%, 93.2%; COX-2 inhibitors, 27.5%, 10%, 87.4%; acetaminophen, 46.0%, 6.5%, 98.7%; tramadol, 44.5%, 8.4%, 95.6%; weak opioids, 27.2%, 4.1%, 98.3%; and strong opioids, 41.1%, 3.3%, 97%. Therapy switching, augmentation, and discontinuation occurred within 2 months after treatment initiation in two thirds of patients and within 6 months in >90% of patients. The patterns of intraarticular injections were significantly different across treatment cohorts, as were the patterns of joint replacement surgeries (both P < 0.0001 for overall effects using log-rank tests), with average times to surgery that appeared longer with acetaminophen, NSAIDs, and COX 2 inhibitor initiators (416-447 days) than with tramadol and opioids (354-385 days). CONCLUSIONS: Results indicate that therapy switching and discontinuation were frequent among OA patients initiating treatment with the currently recommended medication classes and might suggest suboptimal pain relief or potentially intolerable therapy-related side effects. PMID- 22088417 TI - Outcomes of repair of common arterial trunk with truncal valve surgery: a review of the society of thoracic surgeons congenital heart surgery database. AB - BACKGROUND: Previous studies have suggested truncal valve insufficiency may adversely affect outcome after common arterial trunk (CAT) repair. It is unknown if truncal insufficiency requiring truncal valve surgery (TVS) at the time of primary CAT repair impacts outcome. METHODS: Patients in The Society of Thoracic Surgeons Congenital Heart Surgery Database undergoing CAT repair from 2000 to 2009 were included. Outcomes were compared for patients with and without TVS at the time of CAT repair and were further stratified by interrupted aortic arch (IAA) repair. RESULTS: Of 572 patients (63 centers), median age at surgery was 12 days (interquartile range, 6 to 34). Twenty-three patients underwent concomitant TVS (n=22 repair, n=1 replacement) during CAT repair, and 4 patients underwent TVS later during the same hospitalization (n=1 repair, n=3 replacement). Thirty nine patients underwent IAA repair at the time of CAT repair, 5 of whom had concomitant TVS. Mortality for CAT repair with TVS versus isolated CAT repair was 30% versus 10% (p=0.0002). All 4 patients who required TVS later during the admission died. Truncal valve surgery was associated with increased mortality among CAT patients both with and without IAA repair, with the highest mortality (60%) among CAT patients undergoing IAA repair and TVS (n=5). Common arterial trunk plus TVS had an increased risk of mechanical support and a longer hospital stay. CONCLUSIONS: Truncal valve surgery in patients undergoing CAT repair is associated with significant mortality. Repair of IAA and TVS at the time of CAT repair carries particularly high risk. Failure to address significant truncal insufficiency, necessitating early reoperation with TVS, had uniformly poor outcomes. PMID- 22088418 TI - Modified and "reverse" frozen elephant trunk repairs for extensive disease and complications after stent grafting. AB - BACKGROUND: The frozen elephant trunk (FET) repair technique combines conventional arch repair with the patient under circulatory arrest with stent grafting and is increasingly being used to treat extensive thoracic aortic disease. This surgical approach is evolving, including its use for complications after thoracic aortic stent grafting - the so-called reversed frozen elephant trunk (RFET). We evaluated the safety and efficacy of FET and RFET operations in high-risk patients. METHODS: Between July 2001 and December 2010, 31 patients underwent FET and 19 patients underwent RFET for extensive thoracic aortic disease. Causes included aneurysm (n=32), acute dissection (n=17), and rupture (n=1). Twenty-three cases (46%) were for urgent or emergency indications. Patient data and outcomes were collected through a prospectively maintained clinical database and 3-dimensional analysis of computed tomography (CT) scans. Outcomes were assessed using Kaplan-Meier methodology. RESULTS: In-hospital mortality was 8% (n=4, including 1 emergency RFET procedure for aortic rupture and 2 urgent FET procedures for symptomatic degenerative aneurysm). Stroke occurred in 5 patients (10%) and spinal cord injury in 4 patients (8%). Mean hospital stay was 14.3 days (range 4 to 67 days). Five endoleaks were observed (4 type II, 1 type I) requiring 2 endovascular reinterventions. Mean follow-up was 17 months (range, 1 to 76 months) and actuarial survival was 87% at 2 years. CONCLUSIONS: Frozen elephant trunk repair is an effective surgical strategy for managing high-risk patients with extensive pathologic conditions of the thoracic aorta. The RFET approach is a feasible option for proximal aortic complications after previous descending stent grafting. Intermediate outcomes are reasonable for both approaches and further evaluation of these techniques is warranted. PMID- 22088419 TI - Sequential design for clinical trials evaluating a prosthetic heart valve. AB - BACKGROUND: Clinical trials involving prosthetic heart valves are typically based on a set of objective performance criteria for certain late adverse event rates. Typically, these trials require 800 patient-years of data to be collected to provide 80% power while maintaining the type I error at the 0.05 level. METHODS: This work presents a sequential design alternative to the standard objective performance criteria trial that allows for the possibility of stopping the trial early. Logistical issues regarding these designs are considered, and power calculations are provided that investigate the probability of early stopping if the prosthetic valve exceeds expectations with respect to the objective performance criteria end points. RESULTS: Designs exist that provide at least 50% power at the interim look and 80% overall power under the alternative hypothesis. If the prosthetic valve performs better than expected, the interim power may exceed 80%. CONCLUSIONS: The proposed sequential designs can reduce the time required to bring a prosthetic heart valve to market, helping to ensure that patients and clinicians have access to the latest devices in shorter time. PMID- 22088420 TI - Effects of watershed densities of animal feeding operations on nutrient concentrations and estrogenic activity in agricultural streams. AB - Application of manures from animal feeding operations (AFOs) as fertilizer on agricultural land can introduce nutrients and hormones (e.g. estrogens) to streams. A landscape-scale study was conducted in the Shenandoah River watershed (Virginia, USA) in order to assess the relationship between densities of AFOs in watersheds of agricultural streams and in-stream nutrient concentrations and estrogenic activity. The effect of wastewater treatment plants (WWTPs) on nutrients and estrogenic activity was also evaluated. During periods of high and low flow, dissolved inorganic nitrogen (DIN) and orthophosphate (PO(4)-P) concentrations were analyzed and estrogens/estrogenic compounds were extracted and quantified as17beta-estradiol equivalents (E2Eq) using a bioluminescent yeast estrogen screen. Estrogenic activity was measurable in the majority of collected samples, and 20% had E2Eq concentrations >1 ng/L. Relatively high concentrations of DIN (>1000 MUg/L) were also frequently detected. During all sampling periods, there were strong relationships between watershed densities of AFOs and in-stream concentrations of DIN (R(2) = 0.56-0.81) and E2Eq (R(2) = 0.39-0.75). Relationships between watershed densities of AFOs and PO(4)-P were weaker, but were also significant (R(2) = 0.27-0.57). When combined with the effect of watershed AFO density, streams receiving WWTP effluent had higher concentrations of PO(4)-P than streams without WWTP discharges, and PO(4)-P was the only analyte with a consistent relationship to WWTPs. The results of this study suggest that as the watershed density of AFOs increases, there is a proportional increase in the potential for nonpoint source pollution of agricultural streams and their receiving waters by nutrients, particularly DIN, and compounds that can cause endocrine disruption in aquatic organisms. PMID- 22088421 TI - Perception of pesticide use by farmers and neighbors in two periurban areas. AB - Public concern about pesticide use is high although varying with social factors. Individual differences in 'perception' and attitude to pesticide use might be particularly evident in periurban regions where farmers and other people live together. This was investigated using a questionnaire sent to 600 farmers and 600 non-farmers in two periurban areas of Sweden. 'Neighbors'(1) were found to have a more negative attitude to pesticides than farmers, who were slightly positive to the use. Neighbors perceived pesticide use in agriculture to be more harmful to the environment than did farmers and also to reduce the quality of products. Both farmers and neighbors thought that farmers are the predominant users of pesticides. However, reported pesticide users within the home setting were just as common among the neighbors as among the farmers. Perceptions of pesticide use were also found to differ between periurban regions within the country. Attitudes and perceptions of pesticide use, as well as of who is the user, differ based on the group of people in a periurban environment and between different regions. Such differences might play a role for tensions and conflicts in the periurban area of a society and also for regulations of pesticide use. PMID- 22088422 TI - Pesticides in water supply wells in Zealand, Denmark: a statistical analysis. AB - Data from the Danish National Borehole Database are used to predict drinking water well vulnerability to contamination by pesticides, and to identify the dominant mechanisms leading to well pollution in Zealand, Denmark. The frequency of detection and concentrations of 4 herbicides and 3 herbicide metabolites are related to factors accounting for geology (thicknesses of sand, clay and chalk layers), geographical location (distance to surface water and distance to contaminated sites), redox conditions and well depth using logistic regression, the binomial test and Spearman correlation techniques. Results show that drinking water wells located in urban areas are more vulnerable to BAM and phenoxy acids contamination, while non-urban area wells are more subject to bentazone contamination. Parameters accounting for the hydraulic connection between the well and the surface (well depth and thickness of the clay confining layer) are often strongly related to well vulnerability. Results also show that wells close to surface water are more vulnerable to contamination, and that sandy layers provide better protection against the leaching of oxidizable pesticides than clay aquitards, because they are more likely to be aerobic. 4-CPP is observed more often at greater well depth, perhaps because of anaerobic dechlorination of dichlorprop. The field data are used to create a set of probabilistic models to predict well vulnerability to contamination by pesticides. PMID- 22088423 TI - Impact of forest fires on particulate matter and ozone levels during the 2003, 2004 and 2005 fire seasons in Portugal. AB - The main purpose of this work is to estimate the impact of forest fires on air pollution applying the LOTOS-EUROS air quality modeling system in Portugal for three consecutive years, 2003-2005. Forest fire emissions have been included in the modeling system through the development of a numerical module, which takes into account the most suitable parameters for Portuguese forest fire characteristics and the burnt area by large forest fires. To better evaluate the influence of forest fires on air quality the LOTOS-EUROS system has been applied with and without forest fire emissions. Hourly concentration results have been compared to measure data at several monitoring locations with better modeling quality parameters when forest fire emissions were considered. Moreover, hourly estimates, with and without fire emissions, can reach differences in the order of 20%, showing the importance and the influence of this type of emissions on air quality. PMID- 22088424 TI - Blood and urine levels of long half-life toxicants by nativity among immigrants to the United States. AB - One's place of birth is a major determinant of his or her exposure to environmental toxicants. By understanding biological burdens of long half-life toxicants by race and nativity we can better understand geographic variation in toxicant distribution. We used the National Health and Nutrition Examination Survey (1999-2006) biomonitoring data to examine differences in blood and urine levels of long half-life environmental toxicants of foreign-born relative to US born people by race/ethnicity. We log transformed blood and urine measures of 51 environmental toxicants. We then used "seemingly unrelated regression," a robust technique for making multiple comparisons across a group of variables with correlated error terms, to examine differences in blood and urine toxicants by nativity and race. We found that, compared to native-born Americans, the foreign born are generally more likely to be exposed to metals (p<0.001) and organochlorine pesticides (p<0.001), but less likely to be exposed to dioxin-like compounds (p<0.001) or polyflourinated compounds (p<0.001). While levels of toxicants varied greatly by region of birth, US-born participants had consistently higher levels of dioxin-like compounds and polyflourinated compounds. PMID- 22088425 TI - Association of SLCO1B1 1b with peptic ulcer amongst Japanese patients taking low dose aspirin. AB - BACKGROUND: In the recent case-control study, we showed an inverse association between peptic ulcer and angiotensin type 1 receptor (AT1R) blockers (ARBs) or HMG-Co A reductase inhibitors (statins). The aim was to evaluate whether the genotypes of uptake and efflux transporters of ARBs and statins relate to the presence of peptic ulcer and/or ulcer bleeding associated with aspirin use. METHODS: Patients taking 100mg of enteric-coated aspirin for cardiovascular diseases who also participated in endoscopic surveillance were studied. SLCO1B, ABCC2, ABCG2, and MDR1 genotypes were determined by PCR or PCR-RFLP. RESULTS: 492 patients enrolled including 78 with peptic ulcer. The frequencies of the SLCO1B1 521TT genotype were significantly higher in the ulcer group (p=0.006) compared to the controls. After adjustment for significant factors, the SLCO1B1 1b haplotype was significantly associated with peptic ulcer (OR, 3.64; 95% CI, 1.81-7.29). CONCLUSIONS: SLCO1B1 1b haplotype may identify patients at increased risk for aspirin-induced peptic ulcer. PMID- 22088426 TI - A follow-up survey of the integrity of the dermatology National Resident Matching Program. AB - BACKGROUND: Our group's 2009 study of the integrity of the dermatology match revealed that some dermatology program directors violated National Resident Matching Program (NRMP) policy during their communications with applicants. Our group's article concluded with recommendations to change this behavior. OBJECTIVE: We repeated a survey of dermatology applicants to understand if dermatology program personnel behavior has changed since our group's 2009 study of the dermatology match. METHODS: We surveyed 2011 applicants to Department of Dermatology, Stanford University, Palo Alto, CA. The survey was anonymous and available online. RESULTS: Of applicants, 14% were asked to reveal how they intended to rank a program before match day. Of applicants, 32% felt pressured to reveal how they intended to rank programs. Of applicants, 90% were asked about interviews at other programs. Of applicants, 44% were asked about their marital status and 19% were asked if they had children or intended to have children. LIMITATIONS: The response rate for applicants was 53%. CONCLUSION: Although our previous study increased knowledge about the problems within the dermatology match, dermatology program personnel continue to violate NRMP policy. The most widespread violations are asking applicants where they will interview, asking applicants if they are married, and pressuring applicants to reveal how they intend to rank programs. We continue to recommend that programs avoid postinterview contact, and recommend that the NRMP create training videos for applicants and interviewers. PMID- 22088427 TI - Predictive value of margins in diagnostic biopsies of nonmelanoma skin cancers. AB - BACKGROUND: With geographic regional variation, nonmelanoma skin cancer biopsy reports include assessment of margins. When margins are reported as negative, clinical dilemmas may emerge concerning the necessity of additional treatment. OBJECTIVE: To evaluate the predictive value of biopsy margins with regard to residual tumor present in subsequent excisions of nonmelanoma skin cancers. METHODS: This is a retrospective review of 235 diagnostic nonmelanoma skin cancer biopsies and their corresponding excisions for margin status at biopsy, and the presence of residual tumor in subsequent excisions. RESULTS: Twelve of 148 squamous cell carcinomas (8.1%) had negative biopsy margins and all of the subsequent excisions were free of residual tumor. The squamous cell carcinomas with negative biopsy margins consisted predominantly of nonfacial, superficial tumors of the well-differentiated and keratoacanthoma subtype. Nine of 87 basal cell carcinomas (10.3%) had negative biopsy margins. Seven of those 9 (77.8%) had residual tumor present in subsequent excisions. LIMITATIONS: Statistical analysis performed reached significance, but with small sample size as only 21 of the biopsy specimens had negative margins. Also, residual tumor was determined via standard bread-loafing technique on excisions, which is known to examine only a proportion of the tissue and can lead to false-negative results. CONCLUSIONS: The results of this small pilot study suggest that negative-margin diagnostic biopsies may be therapeutic for well-differentiated or keratoacanthoma subtypes of squamous cell carcinoma because all subsequent excisions were devoid of tumor. Negative biopsy margins from basal cell carcinomas were not predictive of tumor removal. PMID- 22088428 TI - Prognostic value of histologic features of toxic epidermal necrolysis. AB - BACKGROUND: The prognosis of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and SJS/TEN overlap syndrome has been assessed using a disease specific severity score (SCORTEN) based on clinical and laboratory data. Histologic data may improve outcome prediction. OBJECTIVE: We sought to evaluate whether dermal mononuclear infiltration and epidermal necrosis predict survival of patients with TEN, SJS, or SJS/TEN. METHODS: We conducted a retrospective review of clinical records and skin biopsy specimens read without knowledge of clinical data. RESULTS: We identified 108 patients (SJS, n = 42; SJS/TEN, n = 36; TEN, n = 30). Overall mortality was 21.3%. Dermal infiltration and epidermal necrosis were not associated with time from disease onset to biopsy. Extensive dermal infiltrates were seen in 19 (18.5%) patients and full-thickness epidermal necrosis in 56 (52%) patients. Dermal infiltrate severity was not associated with day-1 (D1) SCORTEN or hospital death. Epidermal necrosis severity showed trends toward associations with D1 SCORTEN (P = .11) and hospital death (P = .06). In univariate analyses, full-thickness epidermal necrosis was significantly associated with hospital death (32.1% vs 11.4%, P = .017) and worse D1 SCORTEN values (1.98 +/- 1.29 vs 1.55 +/- 1.21; P = .04). In the bivariate analysis, however, D1 SCORTEN remained significantly associated with hospital death (odds ratio = 3.07, 95% confidence interval 1.83-5.16) but the association with full thickness epidermal necrosis was no longer significant (odds ratio = 2.02, 95% confidence interval 0.65-7.12). LIMITATIONS: Retrospective study design and indirect assessment of progression are limitations. CONCLUSION: Full-thickness epidermal necrosis was associated with mortality but did not independently predict hospital death after adjustment based on the SCORTEN value. Dermal infiltrate severity was not associated with hospital death. PMID- 22088429 TI - The risk of nail changes with epidermal growth factor receptor inhibitors: a systematic review of the literature and meta-analysis. AB - BACKGROUND: The overall incidence and risk of nail changes associated with the use of epidermal growth factor receptor inhibitors (EGFRIs) varies widely across the literature. OBJECTIVE: We conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing nail toxicity among patients receiving EGFRIs. METHODS: Databases from Pubmed and Web of Science from January 1998 until July 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through July 2011 were searched to identify relevant studies. The incidence and relative risk (RR) of nail toxicity were calculated using random-effects or fixed-effects model depending on the heterogeneity of the included studies. RESULTS: A total of 2107 patients from 22 clinical trials were included in this analysis. The overall incidence of all grade nail toxicity was 17.2% (95% confidence interval [CI]: 13.8%-21.3%), with an RR of 76.94 (95% CI: 40.76-145.22, P < .001). The overall incidence of high grade nail toxicity was 1.4% (95% CI: 0.9%-2.1%), with an RR of 13.11 (95% CI: 3.73-46.03, P < .001). LIMITATIONS: The ability to detect and grade nail changes may vary among institutions. CONCLUSION: There is a significant risk of developing nail toxicity in cancer patients receiving EGFRIs. The risk is independent of the underlying agent. Adequate monitoring and early intervention are recommended to prevent debilitating toxicity and suboptimal dosing of EGFRI. PMID- 22088430 TI - Antidepressant-like effect of sildenafil through oxytocin-dependent cyclic AMP response element-binding protein phosphorylation. AB - Oxytocin (OT) levels in plasma increase during sexual response and are significantly lower in patients with depression. A drug for the treatment of sexual dysfunction, sildenafil, enhances the electrically evoked release of OT from the posterior pituitary. In this study, we showed that sildenafil had an antidepressant-like effect through activation of an OT signaling pathway. Application of sildenafil reduced depression-related behavior in male mice. The antidepressant-like effect was blocked by an OT receptor (OTR) antagonist and was absent in OTR knockout (KO) mice. Sildenafil increased the phosphorylation of cAMP response element-binding protein (CREB) in the hippocampus. The OTR antagonist inhibited sildenafil-induced CREB phosphorylation and sildenafil had no effect on CREB phosphorylation in OTR KO mice. These results suggest sildenafil to have an antidepressant-like effect through the activation of OT signaling and to be a promising drug for the treatment of depression. PMID- 22088431 TI - Discriminating between maximal and feigned isokinetic knee musculature performance using waveform similarity measures. AB - BACKGROUND: Muscle strength test outcomes may aid in determination of impairment or disability rating following injury. In such settings, verification of participant effort during testing is imperative. This investigation explored the utilization of within-set moment waveform similarity measures, namely cross correlation and percent root mean square difference scores, to develop decision rules for discriminating between maximal and feigned efforts during isokinetic testing of the knee joint musculature. METHODS: A mixed-gender sample of 46 participants performed non-reciprocal sets of maximal or feigned knee extension and flexion concentric and eccentric efforts at testing velocities of 30 degrees s(-1) and 120 degrees s(-1). Logistic regression and Monte Carlo simulations were used to derive decision rules for differentiating between the two effort types. FINDINGS: Employing cutoff scores corresponding to 100% specificity; sensitivities of the knee extensor's velocity-specific decision rules were 92.4% and 84.8%, respectively. The velocity-specific knee flexor's test sensitivities were 56.5% and 46.7%. INTERPRETATION: Utilizing the proposed decision rules, substantiating maximal effort performance of the knee extensors may be possible using this specific testing protocol. However, the proposed methods are limited in their ability to verify performance of maximal knee flexor efforts. PMID- 22088432 TI - Acid increases NHE8 surface expression and activity in NRK cells. AB - We previously demonstrated that there is a paucity of brush-border membrane NHE3 in neonates, the predominant Na(+)/H(+) exchanger in the adult proximal tubule, while NHE8 is relatively highly expressed in neonates compared with adults. We recently showed that metabolic acidosis in neonatal rodents can increase brush border membrane NHE8 protein expression and Na(+)/H(+) exchange activity. To further examine the regulation of NHE8 by acid, we incubated NRK cells, which express NHE8 but not NHE3, with either acid or control media (6.6 vs. 7.4). There was an increase in Na(+)/H(+) exchanger activity within 6 h of incubation with acid media assessed as the rate of sodium-dependent recovery of pH from an acid load (dpH(i)/dt). The acid stimulation persisted for at least 24 h. The increase in Na(+)/H(+) exchange activity was paralleled by an increase in surface expression of NHE8, assessed by surface biotinylation and streptavidin precipitation. The increase in both apical membrane NHE8 protein expression and Na(+)/H(+) exchange activity with pH 6.6 media compared with 7.4 media was not affected by actinomycin D or cycloheximide consistent with an increase in surface expression independent of mRNA or protein synthesis. Furthermore, there was no increase in total cellular NHE8 protein abundance or mRNA abundance with acid media. Finally, we demonstrate that the increase in surface expression of NHE8 with acid media was blocked by colchicine and cytochalasin D and mediated by acid increasing the rate of exocytosis. In conclusion, NHE8 surface expression and activity are regulated by acid media by increasing the rate of trafficking to the apical membrane. PMID- 22088433 TI - Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter. AB - We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na(+) or urea-Cl(-) cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na(+) or urea- Cl(-) cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data. PMID- 22088435 TI - More actors in ammonia absorption by the thick ascending limb. AB - This review will briefly summarize current knowledge on the basolateral ammonia transport mechanisms in the thick ascending limb (TAL) of the loop of Henle. This segment transports ammonia against a concentration gradient and is responsible for the accumulation of ammonia in the medullary interstitium, which, in turn, favors ammonia secretion across the collecting duct. Experimental data indicate that the sodium/hydrogen ion exchanger isoform 4 (NHE4; Scl9a4) is a sodium/ammonia exchanger and plays a major role in this process. Disruption of murine NHE4 leads to metabolic acidosis with inappropriate urinary ammonia excretion and decreases the ability of the TAL to absorb ammonia and to build the corticopapillary ammonia gradient. However, NHE4 does not account for the entirety of ammonia absorption by the TAL, indicating that, at least, one more transporter is involved. PMID- 22088434 TI - Involvement of cytochrome P-450 1B1 in renal dysfunction, injury, and inflammation associated with angiotensin II-induced hypertension in rats. AB - We investigated the contribution of cytochrome P-450 1B1 (CYP1B1) to renal dysfunction and organ damage associated with ANG II-induced hypertension in rats. ANG II (300 ng.kg(-1).min(-1)) or vehicle were infused for 2 wk, with daily injections of a selective CYP1B1 inhibitor, 2,4,3',5'-tetramethoxystilbene (TMS; 300 MUg/kg ip), or its vehicle. ANG II increased blood pressure and renal CYP1B1 activity that were prevented by TMS. ANG II also increased water intake and urine output, decreased glomerular filtration rate, increased urinary Na(+) and K(+) excretion, and caused proteinuria, all of which were prevented by TMS. ANG II infusion caused hypertrophy, endothelial dysfunction, and increased reactivity of renal and interlobar arteries to vasoconstrictor agents and renal vascular resistance and interstitial fibrosis as indicated by accumulation of alpha-smooth muscle actin, fibronectin, and collagen, and inflammation as indicated by increased infiltration of CD-3(+) cells; these effects were inhibited by TMS. ANG II infusion also increased production of reactive oxygen species (ROS) and activities of NADPH oxidase, ERK1/2, p38 MAPK, and c-Src that were prevented by TMS. TMS alone had no effect on any of the above parameters. These data suggest that CYP1B1 contributes to the renal pathophysiological changes associated with ANG II-induced hypertension, most likely via increased ROS production and activation of ERK1/2, p38 MAPK, and c-Src and that CYP1B1 could serve as a novel target for treating renal disease associated with hypertension. PMID- 22088436 TI - Tissue injury after lithium treatment in human and rat postnatal kidney involves glycogen synthase kinase-3beta-positive epithelium. AB - It was hypothesized that lithium causes accelerated and permanent injury to the postnatally developing kidney through entry into epithelial cells of the distal nephron and inhibition of glycogen synthase kinase-3beta (GSK-3beta). GSK-3beta immunoreactivity was associated with glomeruli, the thick ascending limb of Henle's loop, and collecting ducts in the developing and adult human and rat kidney. In rats, the abundance of inactive, phosphorylated GSK-3beta (pGSK-3beta) protein decreased during postnatal development. After feeding of dams with litters lithium [50 mmol Li/kg chow, postnatal (P) days 7-28], the offspring showed plasma lithium concentration of 1.0 mmol/l. Kidneys from lithium-treated rat pups exhibited dilated distal nephron segments with microcysts. Stereological analysis showed reduced cortex and outer medullary volumes. Lithium increased pGSK-3beta and the proliferation marker proliferating cell nuclear antigen (PCNA) protein abundances in the cortex and medulla. After lithium treatment, pGSK-3beta immunopositive cells exhibited restricted distribution and were associated primarily with subsets of cells in dilated and microcystic segments of cortical collecting ducts. After 6 wk of lithium discontinuation, adult rats exhibited attenuated urine concentration capacity and diminished outer medullary volume. Histological sections of two nephrectomy samples and a biopsy from three long term lithium-treated patients showed multiple cortical microcysts that originated from normally appearing tubules. Microcysts were lined by a cuboidal PCNA-, GSK 3beta-, and pGSK-3beta-immunopositive epithelium. The postnatal rat kidney may serve as an experimental model for the study of lithium-induced human kidney injury. The data are compatible with a causal relationship between epithelial entry of lithium into cells of the aldosterone-sensitive distal nephron, inactivation of GSK-3beta, proliferation, and microcysts. PMID- 22088437 TI - Increased urinary protein excretion in the "normal" range is associated with increased renin-angiotensin system activity. AB - Increased levels of albuminuria and proteinuria, both linked to augmented renin angiotensin system (RAS) activity, are associated with adverse kidney and cardiovascular events. However, the relationship between variations in urinary albumin excretion (UAE) and total protein excretion (UTPE) in the normal range and RAS activity is unclear. We examined the association between UAE and UTPE and the hemodynamic response to angiotensin II (ANG II) challenge, a well-accepted indirect measure of RAS activity, in healthy individuals with normal UAE and UTPE. Forty subjects (15 men, 25 women; age 38 +/- 2 yr; UAE, 3.32 +/- 0.55 mg/day; UTPE, 56.8 +/- 3.6 mg/day) were studied in high-salt balance. Blood pressure (BP), arterial stiffness determined by applanation tonometry, and circulating RAS components were measured at baseline and in response to graded ANG II infusion. The primary outcome was the BP response to ANG II challenge at 30 and 60 min. UAE was associated with a blunted diastolic BP response to ANG II infusion (30 min, P = 0.005; 60 min, P = 0.17), a relationship which remained even after adjustment (30 min, P < 0.001; 60 min, P = 0.035). Similar results were observed with UTPE (30 min, P = 0.031; 60 min, P = 0.001), even after multivariate analysis (30 min, P = 0.008; 60 min, P = 0.001). Neither UAE nor UTPE was associated with systolic BP, circulating RAS components, or arterial stiffness responses to ANG II challenge. Among healthy individuals with UAE and UTPE in the normal range, increased levels of these measures were independently associated with a blunted diastolic BP response to ANG II, indicating increased vascular RAS activity, which is known to be deleterious to both renal and cardiac function. PMID- 22088438 TI - L1 cell adhesion molecule and epidermal growth factor receptor activation confer cisplatin resistance in intrahepatic cholangiocarcinoma cells. AB - Intrahepatic cholangiocarcinoma (ICC) is refractory to conventional chemotherapy. We previously generated chemoresistant ICC (SCK(R)) cells and showed that AKT and ERK signaling conferred cisplatin resistance. Here, we report that epidermal growth factor receptor (EGFR) signaling and L1 cell adhesion molecule (L1CAM) conferred cisplatin resistance in SCK(R) cells in an additive fashion. Activation of EGFR connected to AKT and ERK signaling pathways may induce anti-apoptosis and promote cell proliferation, while L1CAM promoted cell proliferation by mainly activating ERK signaling. Inhibition of EGFR activation or L1ACM greatly sensitized the cells to cisplatin. EGFR and L1CAM may be important targets for ICC therapy. PMID- 22088439 TI - Characterization of a cell culture model for clinically aggressive hepatocellular carcinoma induced by chronic hypoxia. AB - We demonstrated in an in vitro model (human HepG2 liver cells) that chronic hypoxia induced gene expression is associated with an aggressive phenotype in patients with hepatocellular carcinoma (HCC). The aim of this study was to characterize this model further using gene expression microarray, real-time PCR and immunocytochemistry. Subsequently, pathway analysis software was used to identify relevant processes. After examination, we selected 2% O2 during 72 h as conditions to study chronic hypoxia. The most affected signaling is centered on TGF-beta1 and PPARalpha/RXRalpha. Cells at 2% O2 showed a shift in expression of Epithelial-to-Mesenchymal-Transition (EMT) related genes. Furthermore, a downregulation of liver specific detoxification pathways including cytochrome P450's and glutathione-S-transferases was observed. Both up- and downregulation events within different signaling cascades indicated a cellular adaptation and the onset of a new equilibrium. The prominent role of TGF-beta1- and PPARalpha/RXRalpha signaling and cell motility pathways warrants their further investigation for therapeutic targets in HCC. PMID- 22088440 TI - The challenges of offering public second trimester abortion services in South Africa: health care providers' perspectives. AB - Around 25% of abortions in South Africa are performed in the second trimester. This study aimed to better understand what doctors, nurses and hospital managers involved in second trimester abortion care thought about these services and how they could be improved. Nineteen in-depth interviews with abortion-related service providers and managers in the Western Cape Province, South Africa, were undertaken. Data were analysed using a thematic analysis approach. Participants expressed resistance to the dilation and evacuation (D&E) procedure, as this required more active provider involvement. Medical abortion was preferred as it required less provider involvement in the abortion process. A shortage of providers willing to perform D&E resulted in most public sector services being outsourced to private sector doctors. Respondents noted an increased demand for services and a concomitant lack of infrastructure, physical space and personnel to respond to these demands, sometimes resulting in fragmented or poor quality care. At medical induction sites, most thought introducing the combined mifepristone-misoprostol regimen would improve service capacity, although they were concerned about cost. Improving contraceptive services was also seen as a much-needed intervention to improve care and prevent abortion. Ongoing training, including values clarification, as well as emotional support and team-building for providers are needed to ensure sustainable, high-quality second trimester abortion services. PMID- 22088441 TI - The Atmospheric Scanning Electron Microscope with open sample space observes dynamic phenomena in liquid or gas. AB - Although conventional electron microscopy (EM) requires samples to be in vacuum, most chemical and physical reactions occur in liquid or gas. The Atmospheric Scanning Electron Microscope (ASEM) can observe dynamic phenomena in liquid or gas under atmospheric pressure in real time. An electron-permeable window made of pressure-resistant 100 nm-thick silicon nitride (SiN) film, set into the bottom of the open ASEM sample dish, allows an electron beam to be projected from underneath the sample. A detector positioned below captures backscattered electrons. Using the ASEM, we observed the radiation-induced self-organization process of particles, as well as phenomena accompanying volume change, including evaporation-induced crystallization. Using the electrochemical ASEM dish, we observed tree-like electrochemical depositions on the cathode. In silver nitrate solution, we observed silver depositions near the cathode forming incidental internal voids. The heated ASEM dish allowed observation of patterns of contrast in melting and solidifying solder. Finally, to demonstrate its applicability for monitoring and control of industrial processes, silver paste and solder paste were examined at high throughput. High resolution, imaging speed, flexibility, adaptability, and ease of use facilitate the observation of previously difficult to-image phenomena, and make the ASEM applicable to various fields. PMID- 22088442 TI - Thermal diffuse scattering in transmission electron microscopy. AB - In conventional transmission electron microscopy, thermal scattering significantly affects the image contrast. It has been suggested that not accounting for this correctly is the main cause of the Stobbs factor, the ubiquitous, large contrast mismatch found between theory and experiment. In the case where a hard aperture is applied, we show that previous conclusions drawn from work using bright field scanning transmission electron microscopy and invoking the principle of reciprocity are reliable in the presence of thermal scattering. In the aperture-free case it has been suggested that even the most sophisticated mathematical models for thermal diffuse scattering lack in their numerical implementation, specifically that there may be issues in sampling, including that of the contrast transfer function of the objective lens. We show that these concerns can be satisfactorily overcome with modest computing resources; thermal scattering can be modelled accurately enough for the purpose of making quantitative comparison between simulation and experiment. Spatial incoherence of the source is also investigated. Neglect or inadequate handling of thermal scattering in simulation can have an appreciable effect on the predicted contrast and can be a significant contribution to the Stobbs factor problem. PMID- 22088443 TI - Design of a hybrid double-sideband/single-sideband (schlieren) objective aperture suitable for electron microscopy. AB - A novel design is described for an aperture that blocks a half-plane of the electron diffraction pattern out to a desired scattering angle, and then--except for a narrow support beam--transmits all of the scattered electrons beyond that angle. Our proposed tulip-shaped design is thus a hybrid between the single sideband (ssb) aperture, which blocks a full half-plane of the diffraction pattern, and the conventional (i.e. fully open) double-sideband (dsb) aperture. The benefits of this hybrid design include the fact that such an aperture allows one to obtain high-contrast images of weak-phase objects with the objective lens set to Scherzer defocus. We further demonstrate that such apertures can be fabricated from thin-foil materials by milling with a focused ion beam (FIB), and that such apertures are fully compatible with the requirements of imaging out to a resolution of at least 0.34nm. As is known from earlier work with single sideband apertures, however, the edge of such an aperture can introduce unwanted, electrostatic phase shifts due to charging. The principal requirement for using such an aperture in a routine data-collection mode is thus to discover appropriate materials, protocols for fabrication and processing and conditions of use such that the hybrid aperture remains free of charging over long periods of time. PMID- 22088444 TI - In-focus electron microscopy of frozen-hydrated biological samples with a Boersch phase plate. AB - We report the implementation of an electrostatic Einzel lens (Boersch) phase plate in a prototype transmission electron microscope dedicated to aberration corrected cryo-EM. The combination of phase plate, C(s) corrector and Diffraction Magnification Unit (DMU) as a new electron-optical element ensures minimal information loss due to obstruction by the phase plate and enables in-focus phase contrast imaging of large macromolecular assemblies. As no defocussing is necessary and the spherical aberration is corrected, maximal, non-oscillating phase contrast transfer can be achieved up to the information limit of the instrument. A microchip produced by a scalable micro-fabrication process has 10 phase plates, which are positioned in a conjugate, magnified diffraction plane generated by the DMU. Phase plates remained fully functional for weeks or months. The large distance between phase plate and the cryo sample permits the use of an effective anti-contaminator, resulting in ice contamination rates of <0.6 nm/h at the specimen. Maximal in-focus phase contrast was obtained by applying voltages between 80 and 700 mV to the phase plate electrode. The phase plate allows for in focus imaging of biological objects with a signal-to-noise of 5-10 at a resolution of 2-3 nm, as demonstrated for frozen-hydrated virus particles and purple membrane at liquid-nitrogen temperature. PMID- 22088445 TI - Multilayer Fresnel zone plate for soft X-ray microscopy resolves sub-39nm structures. AB - Best resolutions in X-ray focusing are obtained to date by using diffractive lenses called Fresnel zone plates (FZPs). Their further improvement is nevertheless hindered by fundamental limitations in the employed manufacturing techniques. Here, we show a novel method to fabricate FZPs based on multilayer deposition with atomic layer deposition (ALD) and subsequent sectioning with focused ion beam (FIB). For the first time a multilayer FZP working in the soft X ray range was prepared and could achieve the best resolution obtained so far for multilayer FZPs by resolving features below 39nm in size in a scanning soft X-ray microscope. The new technique presents high potential for high resolution microscopy in both the soft and hard X-ray range. PMID- 22088446 TI - The degradation of EBSD-patterns as a tool to investigate surface crystallized glasses and to identify glassy surface layers. AB - Surface crystallized samples of glass-ceramics containing cordierite, rhombohedral BaAl2B2O7 and fresnoite were analyzed using electron backscatter diffraction (EBSD). The first two materials were chosen because surface crystallized samples of these materials have previously been shown to contain crystals covered by a very thin layer of glass. In all materials, EBSD pattern degradation occurs if the step size of a scan is chosen to be small. It is shown that the minimum step size enabling an evaluable EBSD-scan increases notably, if the crystals are covered by a thin layer of glass. It is also shown that pattern degradation may be utilized to prove the existence of such a thin glass or otherwise thermally sensitive layer. This provides significant information concerning the nucleation process of glasses also with respect to nucleation theory of glass-ceramics. It is also possible to describe the quantity of crystalline surface covered by the thermally sensitive layer. PMID- 22088447 TI - Idiopathic pulmonary fibrosis in relation to gene polymorphisms of transforming growth factor-beta1 and plasminogen activator inhibitor 1. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrotic lung disease of unknown etiology. Host susceptibility or genetic factors may be important for the predisposition to it. Transforming growth factor-beta1 (TGF-beta1, a potent profibrotic cytokine) and plasminogen activator inhibitor 1 (PAI-1) play important roles in the development of pulmonary fibrosis. The objective of the study was to investigate the association between the gene polymorphisms of TGF-beta1 869 T > C and PAI-1 4G/5G and the susceptibility to IPF in Han ethnicity. METHODS: Polymerase chain reaction (PCR) and restriction fragment length polymorphism were performed to analyse the gene polymorphisms of TGF-beta1 in 869T > C and PAI-1 4G/5G in 85 IPF patients and 85 healthy controls matched in age, gender, race and smoker status. RESULTS: There was a significant difference in 869T > C genotype distribution of TGF-beta1 between IPF cases and controls, a significant negative association between TC genotype and the development of IPF (OR = 0.508, 95%CI: 0.275 - 0.941) and a positive association between CC genotype and the development of IPF (OR = 1.967, 95%CI: 1.063 - 3.641). There was a significant positive association between PAI-1 5G/5G genotype and the development of IPF (OR = 0.418, 95%CI: 0.193 - 0.904). CONCLUSIONS: Gene polymorphisms of TGF-beta1 in 869T > C and PAI-1 4G/5G may affect the susceptibility to IPF in Han ethnicity. Further investigations are needed to confirm these findings and assess their biological significance in the development of the disease in this ethnic population. PMID- 22088448 TI - Rituximab induction therapy in highly sensitized kidney transplant recipients. AB - BACKGROUND: The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients. METHODS: Seven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21-47 years). The duration of hemodialysis was 3-12 months, with a mean duration of 11 months. For 4 patients, this was the second transplant; the previous graft survival time was 2 11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25-37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg * kg(-1) * d(-1)) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m(2)) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery. Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored. RESULTS: No patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post-surgery. Diagnosis of acute rejections was based on the clinical assessments and pathological biopsy results. According to the Banff 07 classification of renal allograft pathology, one of the patients was Ia and the other was IIa; the C4d staining was negative in both patients. One patient received methylprednisolone plus cyclophosphamide and the other received antithymocyte globulin (ATG) therapy, both leading to successful reversion of the acute rejection. All patients were discharged postoperatively and all had normal renal function during the 7th to 12th month follow-up. Pulmonary infection occurred in 1 patient 4 months after surgery and was successfully cured. CONCLUSION: Rituximab induction therapy can reduce the occurrence of postoperative humoral rejection in highly sensitized renal transplant recipients, suggesting that kidney transplantation may be safe and effective for these patients. PMID- 22088449 TI - Phase I trial of icotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in Chinese patients with non-small cell lung cancer. AB - BACKGROUND: The preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer (NSCLC) in a Chinese patient population. METHODS: This was an open-label, phase I, dose escalation, safety/tolerability trial of oral icotinib (100 to 400 mg), administered twice per day for 28-continuous-day cycles until disease progression or undue toxicity. RESULTS: Forty patients with stage IIIB (15%) or IV (85%) NSCLC were included in the study. They had mainly adenocarcinoma (85%), with a performance status (PS) of 0 (45%) or 1 (55%) and less than half the patients (45%) had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash (25%), diarrhea, nausea and abdominal distention. One definite interstitial lung disease (ILD) was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one (2.5%) patient receiving 150 mg gained complete response (CR) that persisted for 44 weeks, seven (17.50%) patients had partial remission (PR), and 18 (45%) patients had stable disease (SD). The objective response including CR + PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks (range: 12 to 32 weeks). The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose, response, adverse effect, or duration of the study was observed. CONCLUSIONS: Icotinib, given as oral twice daily, showed favorable safety and tolerability. Mild and reversible rash, diarrhea, and nausea were the main adverse events. Antitumor activity was obvious at each dose in heavily pretreated patients. Pharmacodynamic evaluations and further phase II/III trials are in progress. PMID- 22088450 TI - Early and long-term results of combined cardiac surgery and neoplastic resection in patients with concomitant severe heart disease and neoplasms. AB - BACKGROUND: It is a surgical dilemma when patients present with both severe heart disease and neoplasms. The best surgical treatment remains controversial. This study aimed to analyze the early and long-term results of simultaneous surgical treatment of severe heart disease and neoplasms. METHODS: We reviewed the clinical records of 15 patients who underwent simultaneous neoplastic resection and cardiac surgery between September 2006 and January 2011. There were 5 male and 10 female patients. The mean age was (59.2 +/- 12.5) years and the mean left ventricular ejection fraction was (57.4 +/- 11.0)%. All patients were followed up completely for a period of 12 to 51 months (mean, (33.1 +/- 11.2) months). RESULTS: Fifteen patients underwent simultaneous cardiac surgery and neoplastic resection. Cardiac procedures consisted of off pump coronary artery bypass grafting (n = 7), aortic valve replacement (n = 3), mitral valve replacement (n = 3), mitral valve replacement with coronary artery bypass grafting (n = 1) and left atrial myxoma resection (n = 1). Neoplastic resection consisted of lung cancer resection (n = 5), colonic cancer resection (n = 3), gallbladder resection (n = 1), colonic cancer resection with gallbladder resection (n = 1), hysterectomy (n = 2), hysterectomy with bilateral salpingo-oophorectomy (n = 2) and left ovariectomy (n = 1). Pathological examination confirmed malignant disease in 10 patients and benign disease in 5 patients. There were no perioperative myocardial infarctions, stroke, pericardial tamponade, renal failure or hospital deaths. The most frequent complications were atrial fibrillation (33.3%), pneumonia (26.7%), low cardiac output syndrome (6.7%) and delayed healing of surgical wounds (6.7%). There was 1 late death 42 months after surgery for recurrent malignant disease. At 1 and 3 years, survival rates were 100% (Kaplan-Meier method). CONCLUSIONS: Simultaneous cardiac surgery and neoplastic resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not appear to adversely affect survival in patients with malignant disease. The long-term survival was determined by tumor stage. PMID- 22088451 TI - Modified culotte stenting for treatment of complex coronary bifurcation lesions: immediate and 9-month outcomes in a pilot study. AB - BACKGROUND: The optimal stenting strategy for the treatment of coronary bifurcation lesions (CBLs) remains uncertain. The present study observed technical feasibility and reliability, 9-month clinical and angiographic outcomes of the modified culotte stenting (MCS) in the treatment of CBLs with drug-eluting stents. METHODS: A total of 34 consecutive patients with CBLs that required stenting the parent vessel (PV), the main branch (MB) and the side branch (SB) were included. All patients were first assigned to receive MCS for CBL interventions (per MCS), and might be switched to receive the double-kissing crush stenting (DKS) in case of temporally acute branch occlusion (per protocol). RESULTS: The immediate angiographic or procedural success was achieved in 33/34 (97%) lesions (patients) per MCS, 34/34 (100%) lesions (patients) per protocol with 100% successful final balloon kissing. The long-term clinical success at 9 months was 94% per MCS and 94% per protocol, only 2 patients had reoccurrence of angina but none of them needed target lesion revascularization. There were no procedure-related biomarker elevation, no in-stent thrombosis peri-procedurally and at 9-month follow-up. Quantitative coronary angiography data at 9 months showed that in-stent (6%) or in-segment (6%) binary stenosis was infrequent, and minimal lumen diameter was significantly reduced but late lumen loss was acceptable with only (0.10 +/- 0.14) mm for PV, (0.21 +/- 0.23) mm for MB and (0.27 +/- 0.32) mm for SB. CONCLUSIONS: MCS for treatment of CBLs that required dual-stent implantation was technically easier and safer, readily to complete final balloon kissing, and was associated with high immediate success and optimal 9-month outcomes. PMID- 22088453 TI - Intrahepatic biliary injuries associated with radiofrequency ablation of hepatic malignancies. AB - BACKGROUND: Biliary injury after radiofrequency ablation can cause serious consequences including death. However, there are limited data regarding bile duct changes with or without complications associated with radiofrequency ablation of hepatic malignancies. This study aimed to assess the incidence, prognosis and risk factors of intrahepatic biliary injury associated with radiofrequency ablation. METHODS: Between June 2001 and January 2009, 638 patients with hepatic malignancies (405 with hepatocellular carcinoma, and 233 with liver metastasis) who had 955 treatment sessions were enrolled in this study. Imaging and laboratory data, the course of treatment, and patient outcomes were reviewed retrospectively. The risk factors of biliary injury and the impact on overall survival of patients were analyzed. The chi-square test, Fisher's exact test, Kaplan-Meier curves and stepwise Logistic regression model were used for statistical analysis where appropriate. RESULTS: Biliary injury was observed in 17 patients after 17 ablation sessions based on imaging findings. The overall incidence of biliary injury was 1.8% (17/955) with an average onset time of 12 weeks (2-36 weeks). Mild, moderate and severe complications of biliary injury were identified in 9, 6 and 2 cases, respectively. The median survival time after detection of biliary injury was 40 months. There seemed no notable difference in overall survival between patients with and those without biliary injuries. By multivariate analysis, vessel infiltration (P = 0.034) and treatment session >= 4 times (P = 0.025) were independent risk factors for biliary injury of hepatocellular carcinoma; while tumor located centrally was the only independent risk factor in the metastasis group (P = 0.043). CONCLUSIONS: The incidence of biliary injury was not frequent (1.8%). Through appropriate treatment, intrahepatic bile duct injuries seemed not affect the patients' long-term survival. Additionally, risk factors may be helpful for selecting radiofrequency ablation candidates and predicting biliary complications. PMID- 22088452 TI - Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma. AB - BACKGROUND: Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4(+) T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells in patients with allergic asthma. METHODS: Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells were determined by flow cytometry. The expression of cytokines in plasma and in the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. RESULTS: The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4(+)CD25(+) Treg cells and plasma IL 10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. CONCLUSIONS: Imbalances in Th1/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma. PMID- 22088454 TI - New prognostic parameters for very-low-risk gastrointestinal stromal tumors. AB - BACKGROUND: According to the National Institutes of Health consensus criteria, gastrointestinal stromal tumors (GISTs) smaller than 2 cm in diameter with less than 5 mitotic figures per 50 high-power fields are considered very-low-risk GISTs, but these two indices alone cannot reliably predict a benign outcome during long-term follow-ups. Therefore, identification of additional parameters for predicting the clinical behavior of GISTs is necessary. METHODS: Eighty-eight patients with tumors that meet the very-low-risk GIST criteria were retrospectively investigated and morphological parameters of tumors associated with the biological behavior of very-low-risk GISTs were evaluated in the present study. The Kaplan-Meier method was used to calculate disease-free survival rates. RESULTS: Eighty-one patients were followed up for one to 16.3 years. Five cases of relapses were identified in the patients. Distinctive infiltrative growth patterns such as muscularis propria, muscularis mucosa, or nerve infiltration were identified by microscopy in 4 patients with the relapse, including three patients who experienced multiple recurrences. The infiltrative growth features became more obvious in multiple recurrent tumors compared to the single recurrent tumor, while only one developed relapse in 76 patients without infiltration (P < 0.0001). CONCLUSION: Microscopic infiltrative growth patterns of the tumor may have clinical significance in predicting the prognosis of very-low-risk GISTs. PMID- 22088455 TI - Environment surveillance of filamentous fungi in two tertiary care hospitals in China. AB - BACKGROUND: Invasive fungal infections have constituted an increasingly important cause of morbidity and mortality in immunocompromised patients. In this study, a surveillance project was conducted in three different intensive care units of two large tertiary hospitals in China. METHODS: A one-year surveillance project was conducted in two tertiary hospitals which located in northern China and southwest China respectively. Air, surfaces and tap water were sampled twice a month in a central intensive care unit, a bone marrow transplant unit, a neurosurgery intensive care unit and a live transplant department. Environmental conditions such as humidity, temperature and events taking place, for example the present of the visitors, healthcare staff and cleaning crew were also recorded at the time of sampling. RESULTS: The air fungal load was 91.94 cfu/m(3) and 71.02 cfu/m(3) in the southwest China hospital and the northern China hospital respectively. The five most prevalent fungi collected from air and surfaces were Penicillium spp., Cladospcrium spp., Alternaria spp., Aspergillus spp. and Saccharomyces spp. in the southwest China hospital, meanwhile Penicillium spp., Fusarium spp., Aspergillus spp., Alternaria spp. and Cladospcrium spp. in the northern China hospital. The least contaminated department was intensive care units, and the heaviest contaminated department was neurosurgery intensive care unit. Seventy three percent of all surfaces examined in the northern China hospital and eighty six percent in the southwest China hospital yielded fungi. Fifty-four percent of water samples from the northern China hospital and forty-nine percent from the southwest China hospital yielded fungi. CONCLUSIONS: These findings suggested that the fungus exist in the environment of the hospital including air, surface and water. Air and surface fungal load fluctuated over the year. Air fungal load was lower in winter and higher in summer and autumn, but seldom exceeded acceptable level. The higher values were created during May to August in the northern China hospital and May to June and September to October in the southwest China hospital. A correlation between air fungal load and humidity, as well as personnel was observed. PMID- 22088456 TI - Role of tumor necrosis factor-alpha in the pathogenesis of atrial fibrillation. AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic proinflammatory cytokine and contributes to many kinds of cardiovascular diseases via its receptors (TNFR1/TNFR2). We hypothesize that TNF-alpha plays a role in the pathogenesis of chronic atrial fibrillation (AF). METHODS: Sixty-seven consecutive patients who were scheduled to have cardiac surgery were enrolled into the study. Thirty-one patients with rheumatic heart disease (RHD) and AF were enrolled as study group (AF group). The sinus rhythm (SR) control groups consisted of 20 patients with RHD and 16 patients with coronary artery disease (CAD). Peripheral blood sample was collected before the operation. About 5 mm(3) left atrial tissue was disserted during the operation and was separated into three parts for Western blotting, real time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) analysis. RESULTS: Compared with the controls (RHD SR and CAD SR), the levels of TNF-alpha ((14.40 +/- 5.45) pg/ml vs. (4.20 +/- 3.19) pg/ml vs. (2.68 +/- 2.20) pg/ml, P = 0.000) and its soluble receptor 1 (sTNFR1) ((1623.9 +/- 558.6) pg/ml vs. (1222.3 +/- 175.6) pg/ml vs. (1387.5 +/- 362.2) pg/ml, P = 0.001) in plasma were higher in patients with AF. TNF-alpha level had positive correlation with the left atrial diameter (LAD) (r = 0.642, P = 0.000). Western blotting analysis showed that the protein levels of TNF-alpha (0.618 +/- 0.236 vs. 0.234 +/- 0.178 vs. 0.180 +/- 0.103, P = 0.000) were higher in patients with AF. The RT-PCR analysis results demonstrated that the mRNA expression of TNF-alpha (0.103 +/- 0.047 vs. 0.031 +/- 0.027 vs. 0.023 +/- 0.018, P = 0.000) increased in patients with AF. IHC analysis displayed that, comparing to the SR, the expression of TNF-alpha (0.125 +/- 0.025 vs. 0.080 +/- 0.027 vs. 0.070 +/- 0.023, P = 0.000) increased in the AF group. The protein level and mRNA expression of TNF-alpha also had positive correlation with left atrium diameter (LAD) (r = 0.415, P = 0.000 and r = 0.499, P = 0.000). CONCLUSIONS: The results revealed that TNF-alpha elevated in the plasma and left atrial tissue and had positive correlation with LAD in patients of chronic AF. TNF-alpha might involve in the pathogenesis of chronic AF. PMID- 22088457 TI - Clinical evaluation of the quantitative locator for conjunctiva resection used as an instrument for the treatment of conjunctivochalasis. AB - BACKGROUND: The crescent excision of the inferior bulbar conjunctiva has been advised as a surgical procedure in the management of conjunctivochalasis refractory to medical treatments. However, it is difficult for this procedure to design how much conjunctival tissue should be excised. This study aimed to present a quantitative locator for conjunctiva resection and evaluate its effect on the treatment of conjunctivochalasis (CCh). METHODS: Poly beta-hydroxyethyl methacrylate resin/beta-hydroxyethyl methacrylate (HEMA, water gel) was used as the material to make the quantitative locator which was designed to suit the specific patient. Forty-six patients with bilateral symptomatic CCh were included in this prospective study. Of the patients, while the right eye underwent the popularly used crescent-shaped conjunctiva resection (group I), the left eye was treated with conjunctiva resection assisted by the quantitative locator (group II). International Ocular Surface Disease Index (OSDI), scores of remnant conjunctiva fold, complications and conjunctival cut healing, height of tear meniscus, tear break-up time (BUT), and time of surgery were evaluated. Tasting chloromycetin test (TCT) was used to evaluate how the lacrimal duct worked. RESULTS: OSDI in group II (8.82 +/- 2.36) was significantly lower than that in group I (14.67 +/- 2.21) (t = 12.22, P < 0.01). The amount of conjunctiva fold remaining in group II was less than that in group I. Scores of remnant conjunctiva fold in group I were significantly higher than those in group II (t = 31.85, P < 0.01). While evaluation scores of conjunctival cut healing in group I were lower than those in group II, scores of complication in group I were significantly higher than those in group II at 8 weeks after surgery (t = 89.60, P < 0.01). There was no significant difference in eyes with normal BUT (chi(2) = 0.031, P = 0.985) between the two groups, as the case was in eyes with positive TCT (chi(2) = 0.14, P = 0.930) and in eyes with normal height of tear meniscus (chi(2) = 0.48, P = 0.780). Mean surgery time in group II ((17.11 +/- 2.08) minutes) was significantly shorter than that in group I ((25.22 +/- 4.78) minutes) (t = 13.84, P < 0.01). CONCLUSION: A quantitative locator can be used as an effective, safe, and less time-consuming instrument to facilitate conjunctival excision for symptomatic CCh treatment. PMID- 22088458 TI - Expression of Smad7 inhibits fibrogenic responses of keratocytes to transforming growth factor beta2. AB - BACKGROUND: Transforming growth factor beta (TGFbeta) is one of the most important growth factors in the development of fibrosis and scarring on cornea. Smad7, an inhibitory Smad, can inhibit TGFbeta signal transduction. In recent years, effects of lentiviral-mediated Smad7 on inhibition of fibrosis on some organs have been studied, while little is known about the effects on cornea. This study aimed to determine the effects of lentiviral-mediated Smad7 gene expression on keratocyte proliferation and fibrosis induced by TGF beta2 in vitro. METHODS: Keratocytes were cultured from corneal tissue isolated from Sprague-Dawley (SD) rats and transfected with Smad7 expressing lentiviral vector (Lv-Smad7) or non functioning control vector (Lv-blank). Following the exposure to TGFbeta2, keratocytes were processed for immunoblotting to assess the phosphorylation of Smad2 as down-stream event of TGFbeta/Smad signaling. Expression of fibrotic markers alpha-smooth muscle actin (alpha-SMA), type III collagen (collagen III) were measured by Western blotting and quantitative real time polymerase chain reaction (PCR). Overall cell proliferation was determined by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the expression of cell cycle-related marker Ki67 at both mRNA and protein levels. RESULTS: The Smad7 gene transfer suppressed TGFbeta/Smad signaling in keratocytes by down regulating phosphorylation of Smad2. Markers of cell proliferation and fibrosis including Ki67, alpha-SMA, collagen III were inhibited by introduction of Smad 7 into TGFbeta exposed keratocytes. Consequently, the rate of cell proliferation was attenuated. CONCLUSION: Smad7 gene transfer inhibited fibrogenic responses of keratocytes to TGFbeta2. PMID- 22088459 TI - Growth of G422 glioma implanted in the mouse brain was affected by the immune ability of the host. AB - BACKGROUND: It is generally accepted that gliomas are the most common primary brain tumors with poor prognosis. We aimed to explore the relationship of the immunity of the central nervous system and the genesis and development of glioma. METHODS: G422 glioma was implanted in the brain of BALB/c mice (immuno-competent mice), nude mice (T cell related immuno-deficient) and complement C3 knock-out mice (complement C3 related immunodeficient). The survival time of the host, growth and histopathology of the tumor, and concentrations of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (INF-gamma) in tumor tissues were assessed. RESULTS: Tumor spheres were formed in all mice after injection, and glial fibrillary acidic protein (GFAP) positive staining of the cells declared their glioma origin. The longest median survival time of (44.3 +/- 6.0) days was found in BALB/c mice, followed by (24.8 +/- 5.2) days in nude mice and the shortest (18.6 +/- 5.8) days in complement C3 knock-out mice. Accordingly, the growth of the tumor was fastest in complement C3 knock-out mice, followed by the nude mice and slowest in the BALB/c mice. Although the proportions of infiltrating CD68(+) lymphocytes in tumor tissues showed no significant difference (P > 0.05), TNF-alpha level in the nude and C3 knock-out mice, (28.11 +/- 4.86) umol/L and (22.87 +/- 6.36) umol/L respectively, were significantly lower (P < 0.01) than that in the BALB/c mice, which was (230.21 +/- 39.17) umol/L. The INF-gamma level was highest in the BALB/c mice ((180.76 +/- 29.19) umol/L), followed by the nude mice ((113.46 +/- 23.76) umol/L) and then the C3 knock-out mice ((16.84 +/- 4.45) umol/L). CONCLUSIONS: The G422 glioma implanted in the brains of mice with different immune ability would be a useful model for studying the relationship of the immune system and tumor in the central nervous system. Furthermore, the T cells and complement C3 compartments of the immune response may affect the growth of implanted tumors and inflammatory factors such as TNF-alpha and INF-gamma. PMID- 22088460 TI - Sutureless choledochoduodenostomy with an intraluminal degradable stent in dog model. AB - BACKGROUND: It is difficult and time-consuming for carrying out conventional hand sewn bilioenteric anastomosis, especially for small bile duct anastomosis and laparoscopic procedure. In order to simplify it, we have developed a novel procedure of sutureless bilioenteric anastomosis with an intraluminal degradable stent. This study aimed to evaluate the feasibility and safety of this technique with cholangioduodenostomy in dog model. METHODS: A patent intraluminal degradable stent tube for sutureless choledochoduodenostomy in dog model was made with polylactic acid in diameter of 3 mm or 4 mm. Thirty-eight dogs were randomly divided into to a stent group (SG, n = 20) and a control group (CG, n = 18). Dogs in the SG underwent sutureless choledochoduodenostomy with intraluminal stent, while the CG underwent conventional choledochoduodenostomy (single layer discontinuous anastomosis with absorbable suture). Dogs of each group were divided into 4 subgroups according to time of death (1, 3, 6, and 12 months postoperatively) to evaluate the healing of anastomosis. Operation time, intraoperative tolerance pressure of anastomosis, rate of postoperative bile leakage, bursting pressure of anastomosis were compared between the two groups. Anastomosis tissue was observed afterwards by pathology evaluation, hydroxyproline content, serum bilirubin, liver enzyme level and magnetic resonance cholangio-pancreatography (MRCP) to assess the stricture. RESULTS: All procedures were completed successfully. The surgical time of the SG was significantly less than the CG (SG: (19.2 +/- 4.3) minutes, vs. CG: (29.2 +/- 7.1) minutes, P = 0.000). One bile leakage was occurred in either group. No significant difference of intraoperative tolerance pressure of anastomosis, rate of bile leakage and postoperative bursting pressure of anastomosis, anastomotic stricture, hydroxyproline content, serum bilirubin and liver enzyme level was found between the two groups. MRCP showed no anastomosis stricture and obstruction during months of follow-up. CONCLUSION: The technique of sutureless choledochoduodenostomy with a degradable intraluminal stent is feasible and a safe procedure in this dog model. PMID- 22088461 TI - Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats. AB - BACKGROUND: Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats. METHODS: Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-alpha (TNF-alpha) levels. Infarct volume was assessed with 2,3,5 triphenyltetrazolium chloride (TTC) staining. RESULTS: The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-alpha levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-alpha levels (P < 0.05). CONCLUSIONS: Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators. PMID- 22088462 TI - Autologous nucleus pulposus transplantation to lumbar 5 dorsal root ganglion after epineurium dissection in rats: a modified model of non-compressive lumbar herniated intervertebral disc. AB - BACKGROUND: Nucleus pulposus of intervertebral discs has proinflammatory characteristics that play a key role in neuropathic pain in lumbar herniated intervertebral disc. One of the most commonly used animal models (the traditional model) of non-compressive lumbar herniated intervertebral disc is created by L4 L5 hemilaminectomy and the application of autologous nucleus pulposus to cover the left L4 and L5 nerve roots in rats. However, such procedures have the disadvantages of excessive trauma and low success rate. We proposed a modified model of non-compressive lumbar herniated intervertebral disc in which only the left L5 dorsal root ganglion is exposed and transplanted with autologous nucleus pulposus following incision of epineurium. We aimed to compare the modified model with the traditional one with regard to trauma and success rate. METHODS: Thirty Sprague-Dawley male rats were randomized into three groups: sham operation group (n = 6), traditional group (n = 12), and modified group (n = 12). The amount of blood loss and operative time for each group were analyzed. The paw withdrawal threshold of the left hind limb to mechanical stimuli and paw withdrawal latency to heat stimuli were examined from the day before surgery to day 35 after surgery. RESULTS: Compared with the traditional group, the modified group had shorter operative time, smaller amount of blood loss, and higher success rate (91.7% versus 58.3%, P < 0.05). There was no decrease in paw withdrawal latency in any group. The sham operation group had no decrease in postoperative paw withdrawal threshold, whereas the modified and traditional groups had significant reduction in paw withdrawal threshold after surgery (mechanical hyperalgesia). CONCLUSIONS: Transplantation of nucleus pulposus onto the L5 dorsal root ganglion following incision of epineurium in rats established an improved animal model of non-compressive lumbar herniated intervertebral disc with less trauma and more stable pain ethology. PMID- 22088463 TI - Effects of HepII domain peptides V of fibronectin on corneal permeability, endothelial cells, intraocular pressure and morphology of trabecular meshwork in rats. AB - BACKGROUND: Trabecular meshwork (TM) cell volume may be an important determinant of aqueous humor outflow in the eye. This study aimed to evaluate the role of HepII domain peptides V on corneal permeability, corneal endothelial cells, intraocular pressure (IOP) and morphology of trabecular meshwork in rats. METHODS: The IOP of rat eyes was measured before and 3, 5, 7 and 8 hours after topical delivery of HepII domain peptides V through intracameral injections. The peptide's concentration in aqueous humor was assessed by high performance liquid chromatography (HPLC). The shape and density of endothelial cells were observed by laser confocal microscopy 8 hours, 3 and 14 days after intracameral injections of HepII domain peptides V. The morphological changes in TM of rat eyes were assessed by transmission electron microscopy (TEM). RESULTS: Intracameral injection of HepII domain peptides V significantly (P < 0.001) decreased IOP by (5.71 +/- 2.10) mmHg in rats at 5 hours after injection. There were no obvious changes of the shape and the density of corneal endothelial cells. In addition, morphological changes in the TM of rats were observed including the expansion of intercellular spaces in the juxtacanalicular meshwork, removal of extracellular material, cellular relaxation, and cytoskeleton reorganization. CONCLUSIONS: HepII domain peptides V could not penetrate cornea and was safe to corneal endothelial cells. HepII domain peptides V could significantly decrease IOP in rat probably by disorganizing actin cytoskeleton and cell-junction in the TM. PMID- 22088464 TI - Downregulation of Rho associated coiled-coil forming protein kinase 1 in the process of delayed myocardialization of cardiac proximal outflow tract septum in connexin 43 knockout mice embryo. AB - BACKGROUND: The connexin43 knockout (Cx43 KO) mouse dies at birth with an enlarged conotruncal region, which leads to the obstruction of the right outflow tract (OFT). Since myocardialization of the proximal OFT septum is one of the key events during heart development, we investigated the process in the Cx43 KO embryo hearts. Rho associated coiled-coil forming protein kinase 1 (ROCK1), is a recently found key molecule to regulate the myocardialization of OFT, but its spatiotemporal expression pattern during myocardialization remains unknown. The objective of this study was to investigate the differentially expressed pattern of ROCK1 between Cx43 KO and wild type embryo hearts, and its relationship with the delayed myocardialization in Cx43 KO embryo hearts. METHODS: Using immunohistochemistry, the processes of myocardiolization were investigated both in Cx43 KO and wild type embryo hearts. The differentially expressed pattern of ROCK1 between Cx43 KO and wildtype embryo hearts was evaluated both at the mRNA and protein level by real-time RT-PCR and immunohistochemistry. RESULTS: The expression of alpha-sarcomeric actin (alpha-SCA) in the proximal OFT septum of Cx43 KO embryos was delayed. Meanwhile, it was shown that the downregulation of ROCK1 coincided with delayed myocardialization. The expression of ROCK1 protein was mainly limited to the proximal outflow tract septum from embryo day (E) E11.5 to E15.5. Its expression pattern was similar with that of alpha-SCA. Real-time RT PCR found that the expression level of Rock-1 mRNA began at a low level on E11.5 and reached peak at E13.5 and E14.5. CONCLUSIONS: ROCK1 may have an important role in the process of myocardialization of the proximal OFT septum. Downregulation of ROCK1 is likely to contribute to the aberrant myocardialization in Cx43 KO embryo hearts. PMID- 22088465 TI - Establishment and gene expression profiling of LKB1 stable knockdown lung cancer cell line. AB - BACKGROUND: Lung cancer is the leading cause of cancer-related death in China. Mutation analysis reveals that LKB1 inactivation is present in 30% of non-small cell lung cancer (NSCLC), indicating its role as a tumor suppressor. However, the molecular mechanism is still not clear. Our study attempted to establish LKB1 stable knockdown NSCLC cell line, detect alterations in gene expression and identify the genes regulated by LKB1. METHODS: LKB1 stable knockdown H1299 cell line was established using a lentiviral short hairpin RNA. To identify the knockdown effect, LKB1 mRNA and protein expression level were evaluated with quantitative real-time PCR and Western blotting. We treated the cell lines with 2 deoxyglucose to determine if LKB1 protein function was impacted. Gene microarray analysis was performed to detect the gene expression alterations in LKB1 stable knockdown H1299 cells. RESULTS: LKB1 mRNA and protein expression were significantly suppressed in LKB1 stable knockdown H1299 cell line. 2-DG treatment had little impact on the phosphorylation of AMPK, which is the downstream target of LKB1, indicating the loss of function of LKB1. The microarray data showed that LKB1 knockdown resulted in expression alterations of 1243 kinds of genes, including those involved in cell migration, cell proliferation and cell apoptosis. CONCLUSIONS: The establishment of LKB1 stable knockdown H1299 cell line provides us with a great tool to investigate various genes regulated by LKB1 through microarray. The discovery of cell proliferation and migration-related genes regulated by LKB1 is critical for unraveling molecular mechanisms of LKB1's role in the development and metastasis of lung cancer. PMID- 22088466 TI - Osteoprotegerin and osteoprotegerin ligand expression during human marrow stromal cell differentiation and their effect on osteoclast formation. AB - BACKGROUND: Osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL) play an important role in human bone metabolism. The aim of this research was to detect the expression of OPG and OPGL during human marrow stromal cells (hMSC) differentiation into osteoblasts (OB), and to observe their effect on osteoclasts (OC) formation in vitro to investigate bone metabolism mechanisms. METHODS: hMSCs were obtained from human bone marrow specimens using gradient centrifugation method, before being purified and incubated with differentiation medium to develop along the human osteoblasts (hOB) pathway. Morphology observation, biochemical detection and cell staining were performed during hMSC differentiation. OPG and OPGL mRNA levels were detected by reverse transcription polymerase chain reaction. OPG and OPGL protein expression were determined by Western blotting. We further obtained OC progenitor cells from mice bone marrow and co-cultured with differentiating MSCs. We assessed the effect of OPG and OPGL on OC formation by identifying tartrate resistant acid phosphatase (TRAP) positive multinuclear cells. RESULTS: Optimal hMSC survival and purification were observed, along with stable biochemical indexes. Alkaline phosphatase secretion increased significantly and mineralization nodules appeared in the process of cell differentiation. OPG mRNA and protein level increased significantly, while OPGL mRNA and protein level decreased. Average levels of OPG mRNA and protein were about 2.5-fold higher than the control, while OPGL mRNA and protein levels were reduced by about one-half. In the group co-culturing with undifferentiated MSC or added OPGL, we found TRAP positive and multi- nuclear OC formation. However, OC formation was absent in the group co-culturing with differentiated MSC or added OPG. CONCLUSIONS: During hMSC differentiation into hOB, OPG secretion increased rapidly and OPGL production decreased significantly. The OPG/OPGL ratio was also increased, while OC formation was inhibited and bone absorption decreased. Thus, regulation of the OPG/OPGL ratio may be important in controlling MSC differentiation, OB and OC formation in succession involved in bone metabolism. PMID- 22088467 TI - Induction of actin disruption and downregulation of P-glycoprotein expression by solamargine in multidrug-resistant K562/A02 cells. AB - BACKGROUND: Solamargine (SM), a steroidal glycoalkaloid isolated from the Chinese herb Solanum incanum, has been shown to inhibit the growth of some cancer cell lines and induce significant apoptosis. However, the effects of SM on multidrug resistant (MDR) cells and the molecular mechanisms involved are poorly understood. The purpose of this study was to evaluate the anti-MDR effects of SM and the associated mechanisms in MDR K562/A02 cells. METHODS: The cytotoxicity of SM was measured by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. The 14',6-diamidino-2-phenylindole (DAPI) nuclear staining and flow cytometry were used to detect SM-induced apoptosis. The mRNA expression of P glycoprotein (P-gp) was investigated by real-time PCR (RT-PCR). Western blotting was used to determine the expression of Bcl-2, Bax, and actin. The changes in the morphology of actin were examined with immunofluorescence staining. RESULTS: MTT results showed that SM effectively killed the MDR sublines K562/A02, KB/VCR, and H460/paclitaxel (Taxol), and their parental cell lines K562, KB, and H460 to an equivalent or more sensitive degree. Based on the results by flow cytometry and immunostaining, the pro-apoptotic effects of SM were observed in MDR K562/A02 cells. Furthermore, the RT-PCR results showed that SM induced the downregulation of MDR1 mRNA. In addition, the expression of P-gp and actin was decreased in the SM-treated cells, as measured by western blotting and immunostaining. CONCLUSIONS: These results demonstrate that SM effectively triggers apoptosis in MDR tumor cells, which is associated with actin disruption and downregulation of MDR1 expression. This compound may merit further investigation as a potential therapeutic agent that bypasses the MDR mechanism for the treatment of MDR tumors. PMID- 22088468 TI - Clinicopathologic and prognostic implications of progranulin in breast carcinoma. AB - BACKGROUND: Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. Its expression is closely correlated with the development and metastasis of several cancers. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathologic features in breast carcinoma biopsies, and the role of progranulin as a new marker of metastatic risk and prognosis in breast cancer has not yet been studied. The aim of this study was to investigate the clinicopathologic and prognostic implications of progranulin expression in breast carcinoma and its correlation with tumor angiogenesis. METHODS: Progranulin expression was determined immunohistochemically in 183 surgical specimens from patients with breast cancer and 20 tissue samples from breast fibroadenomas. The tumor angiogenesis-related biomarker, vascular endothelial growth factor was assayed and microvessel density was assessed by counting vascular endothelial cells in tumor tissues labeled with endoglin antibody. The relationship between progranulin expression and the clinicopathologic data were analyzed. RESULTS: Progranulin proteins were overexpressed in breast cancer. The level of progranulin expression was significantly correlated with tumor size (P = 0.004), lymph node metastasis (P < 0.001) and TNM staging (P < 0.001). High progranulin expression was associated with higher tumor angiogenesis, reflected by increased vascular endothelial growth factor expression (P < 0.001) and higher microvessel density (P = 0.002). CONCLUSION: Progranulin may be a valuable marker for assessing the metastasis and prognosis of breast cancer, and could provide the basis for new combination regimens with antiangiogenic activity. PMID- 22088469 TI - Taxonomic analysis of cryptococcus species complex strain S8012 revealed Cryptococcus gattii with high heterogeneity on the genetics. AB - BACKGROUND: Initially, Cryptococcus (C.) neoformans was previously divided into two varieties comprising C. neoformans var. neoformans and C. neoformans var. gattii. Currently, taxonomic studies defined C. neoformans as C. species complex, which contains C. neoformans var. neoformans (serotype D), the hybrid isolates (serotype AD), C. neoformans var. grubii (serotype A) and C. gattii (serotypes B and C). However, Liao and his team once isolated a unique C. gattii isolate, namely strain S8012 with unique phenotype from cerebrospinal fluid (CSF) of a 43 year-old male patient in the Shanghai Changzheng Hospital and described as C. neoformans var. shanghaiensis in 1980s. The aim of this study was to explore the genetic background and polymorphism of Chinese clinical C. gattii isolates. METHODS: S8012 was analyzed as representative strain using the M13-polymerase chain reaction (PCR) fingerprinting pattern and multilocus sequence analysis including internal transcribed spacers of rDNA (ITS region), the intergenic spacer 1 regions (IGS1), RPB1, RPB2, CNLAC1, and TEF1 genes. RESULTS: The PCR fingerprinting pattern results showed strain S8012 belonged to molecular types VGI, and phylogenetic analysis suggested strain S8012 was grouped into the cluster of C. gattii environmental isolates originated from Eucalyptus camaldulensis trees in Australia. CONCLUSION: C. gattii isolates from Chinese patients expresses high polymorphism on the phenotype, and molecular type VGI isolates from China have a close genetic relationship with the C. gattii isolates from Australia. PMID- 22088470 TI - Genomics of hepatitis B virus-related hepatocellular carcinoma and adjacent noncancerous tissues with cDNA microarray. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a common primary cancer frequently associated with hepatitis B virus (HBV) infection. However, whether these identified genes are particularly associated with HBV-related HCC remains unknown. The aim of this study was to investigate the differential gene expression between HBV-related HCC tissues and adjacent noncancerous tissues. METHODS: cDNA microarray was used to detect the differential gene expression profile in the HBV-related HCC tissues and adjacent noncancerous tissues, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to verify the differential expression of candidate genes obtained from cDNA microarray experiment. RESULTS: In this study, 1369 genes or expressed sequence tags (ESTs) including 121 genes or ESTs with at least two-fold expression alterations between cancerous and noncancerous tissues were identified. Special AT-rich sequence binding protein 1 (SATB-1) expression was positive in 73% (16/22) of cancerous tissues and negative (0/22) in all noncancerous tissues of HBV-related HCC patients. Transmembrane 4 superfamily member 1 (TM4SF-1) expression was positive in 86% (19/22) of cancerous tissues and negative (0/22) in all noncancerous tissues. Suppression of tumorigenicity 14 (ST-14) expression was positive in 73% (16/22) of noncancerous tissues in patients with HBV-related HCC and negative in all HCC tissues (0/22). CONCLUSION: This study provided the gene expression profile of HBV-related HCC and presented differential expression patterns of SATB 1, TM4SF-1 and ST-14 between cancerous and noncancerous tissues in patients with HBV-related HCC. PMID- 22088471 TI - Novel mutations of PRSS1 gene in patients with pancreatic cancer among Han population. AB - BACKGROUND: A high mortality rate of pancreatic cancer becomes a bottleneck for further treatment with long-term efficacy. It is urgent to find a new mean to predict the early onset of pancreatic cancer accurately. The authors hypothesized that genetic variants of cationic trypsinogen (PRSS1) gene could affect trypsin expression/function and result in abnormal activation of protease activated receptor-2 (PAR-2), then lead to pancreatic cancer. The aim of this study was to elaborate some novel mutations of PRSS1 gene in the patients with pancreatic cancer. METHODS: Totally 156 patients with pancreatic cancer and 220 unrelated individuals as controls were enrolled in this study. The mutations of PRSS1 gene were analyzed by direct sequencing. K-ras Mutation Detection Kit was used to find the general k-ras gene disorder in the pancreatic cancer tissue. Then the clinical data were collected and analyzed simultaneously. RESULTS: There were two patients who carried novel mutations which was IVS 3 + 157 G > C of PRSS1 gene in peripheral blood specimens and pancreatic cancer tissue. What's more, it was surprising to find a novel complicated mutation of exon 3 in PRSS1 gene (c.409 A > G and c.416 C > T) in another young patient. The complicated mutation made No. 135 and No. 137 amino acid transfer from Thr to Ala and Thr to Met respectively. No any mutation was found in the normal controls while no mutations of k-ras gene were detected in the three patients. CONCLUSION: Mutations of PRSS1 gene may be an important factor of pancreatic cancer. PMID- 22088472 TI - Magnetic resonance imaging and magnetic resonance angiography in severe crush syndrome with consideration of fasciotomy or amputation: a novel diagnostic tool. PMID- 22088473 TI - Intensive chromic acid burns and acute chromium poisoning with acute renal failure. PMID- 22088474 TI - Sarcomatoid carcinoma of the renal pelvis in duplex kidney. PMID- 22088476 TI - Analytical methods for brain targeted delivery system in vivo: perspectives on imaging modalities and microdialysis. AB - Since the introduction of microdialysis in 1974, the semi-invasive analytical method has grown exponentially. Microdialysis is one of the most potential analysis technologies of pharmacological drug delivery to the brain. In recent decades, analysis of chemicals targeting the brain has led to many improvements. It seems likely that fluorescence imaging was limited to ex vivo and in vitro applications with the exception of several intravital microscopy and photographic imaging approaches. X-ray computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have been commonly utilized for visualization of distribution and therapeutic effects of drugs. The efficient analytical methods for studies of brain-targeting delivery system is a major challenge in detecting the disposition as well as the variances of the factors that regulate the substances delivery into the brain. In this review, we highlight some of the ongoing trends in imaging modalities and the most recent developments in the field of microdialysis of live animals and present insights into exploiting brain disease for therapeutic and diagnostics purpose. PMID- 22088477 TI - Comprehensive investigation of the influence of acidic, basic, and organic mobile phase compositions on bioanalytical assay sensitivity in positive ESI mode LC/MS/MS. AB - The sensitivity and accuracy of a bioanalytical method is critical in defining the pharmacokinetic (PK) parameters of a potential new chemical entity (NCE). Inhaled therapeutics and low dose NCEs present one of the most significant analytical challenges to the bioanalyst, due to their low systemic concentration. The sensitivity of a bioanalytical LC/MS/MS based assay can be influenced by multiple parameters, including: mobile phase composition, extraction efficiency and chromatographic performance. In this work, we discuss the influence of acidic (pH 3), and basic (pH 10) aqueous mobile phases in conjunction with the two most common organic modifiers used in HPLC, acetonitrile and methanol, on the assay sensitivity of twenty-four probe pharmaceuticals in solvent and biological fluid extract. The study showed that when the test probe pharmaceuticals were analyzed with basic aqueous mobile phases compared to standard acidic conditions the following results were observed: increases in chromatographic peak area ranging from 1.2 to 9.6 fold for twenty-one of the test compounds as well as increased signal-to-noise for greater than seventy percent of the compounds. This observed increase in the MS response was not necessarily related to the later elution of the analyte in a higher organic composition under basic conditions. This was demonstrated as seven out of the twenty-four (approximately thirty percent) of the probe pharmaceuticals tested, eluted earlier, or with the same retention time, under basic conditions, and still produced a greater signal-to-noise when analyzed under these basic conditions. Also observed were decreases in chromatographic peak width, and increases in the retention time of very hydrophilic pharmaceutical compounds. The effect of the mobile phase combinations on the retention and MS response of the choline-containing phospholipids present in precipitated plasma was also investigated, as these analytes are a major source of interference when developing a bioanalytical assay. PMID- 22088479 TI - Forced degradation studies of rapamycin: identification of autoxidation products. AB - The immunosuppressant drug rapamycin, also known as Sirolimus, underwent autoxidation under mild conditions to give numerous monomeric and oligomeric compounds, which were generally characterized by size-exclusion chromatography and NP-HPLC with UV and MS detection. Some of the more predominant products, epoxides and ketones, were isolated and identified. Two epoxides and 10S-epimer of rapamycin were described for the first time. Observed rapamycin isomers were also addressed. Computational chemistry was used to provide mechanistic insights. Formation of the majority of the rapamycin products could be rationalized with free radical-mediated autoxidation reactions involving alkene and alcohol sites. Methodological aspects of oxidative stress testing are discussed. PMID- 22088480 TI - Effects of valproate on glutamate metabolism in rat brain slices: a (13)C NMR study. AB - Sodium valproate is a drug widely used for the treatment of epilepsy and mood disorders. We studied the effect of valproate on cerebral energy metabolism by incubating rat brain slices with 5 mM [3-(13)C]glutamate in the absence and the presence of 1 mM valproate. Substrate removal and product formation were measured by enzymatic and carbon 13 NMR methods. Fluxes through the enzymatic steps involved were calculated with an original mathematical model. We demonstrate that, in the presence of valproate, glutamate consumption and aspartate accumulation and labeling were inhibited, whereas GABA accumulation and labeling were increased. Consistent with these observations, this drug inhibited the unidirectional flux from glutamate to alpha-ketoglutarate and fluxes through several enzymes (gamma aminobutyric acid aminotransferase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, aspartate aminotransferase, malic enzyme, pyruvate dehydrogenase, pyruvate carboxylase and citrate synthase). By contrast, glutamic acid decarboxylase flux was increased. With 2 mM glutamate+1 mM valproate and with 5 mM glutamate+2 mM valproate, GABA and aspartate labelings were similarly altered. On the basis of the effects of valproate, it is concluded that our cellular model and our cellular metabolomic approach appear suitable to study the beneficial and adverse interactions of neurotropic compounds with the cerebral metabolic pathways. PMID- 22088481 TI - Premonitory features and seizure self-prediction: artifact or real? AB - Seizure prediction is currently largely investigated by means of EEG analyses. We here report on evidence available on the ability of epilepsy patients themselves to predict seizures either by means of subjective experiences ("prodromes"), apparent awareness of precipitants, or a feeling of impending seizure (self prediction). These data have been collected prospectively by paper or electronic diaries. Whereas evidence for a predictive value of prodromes is missing, some patients nevertheless can forsee impending seizures above chance level. Relevant cues and practical implications are discussed. PMID- 22088482 TI - ZSTK474, a specific phosphatidylinositol 3-kinase inhibitor, induces G1 arrest of the cell cycle in vivo. AB - Phosphatidylinositol 3-kinase (PI3K) is regarded as a promising therapeutic target because it is often activated in cancer. We previously reported that ZSTK474, a specific PI3K inhibitor, inhibits tumour cell proliferation via G1 arrest of the cell cycle without inducing apoptosis in vitro. However, it remained unclear whether ZSTK474 induces G1 arrest to exert antitumour efficacy in vivo. We recently developed a live imaging system, named Fluorescent Ubiquitination-based Cell Cycle Indicator (Fucci), to visualise cell cycle distribution. Here, by using this system, we tested whether ZSTK474 induces G1 arrest in tumour cells in vivo, as well as in vitro. Fucci-introduced human breast cancer MCF-7 cells and cervical cancer HeLa cells were subcutaneously xenografted in nude mice. ZSTK474 was administered to the tumour-bearing mice for 5 days, and the cell cycle distribution in the xenografted tumours were analysed by monitoring fluorescence in live mice. We demonstrate that ZSTK474 induces G1arrest along with tumour suppression in vivo. Moreover, we show that ZSTK474 suppresses the tumour growth without inducing apoptosis. Interestingly, such increase in G1 cells and tumour suppression was maintained during long-term (3 month) administration of ZSTK474. These results suggest that ZSTK474 exerts its in vivo antitumour efficacy via G1 arrest but not via apoptosis as long as it is administered, and could be used for months as maintenance therapy for patients with advanced cancers. PMID- 22088483 TI - Concurrent infections with multiple human papillomavirus (HPV) types in the New Technologies for Cervical Cancer (NTCC) screening study. AB - INTRODUCTION: We investigated clustering patterns of human papillomavirus (HPV) in a large study, the New Technologies in Cervical Cancer (NTCC) screening study. MATERIALS AND METHODS: Women aged 25-60 years who attended cervical screening in eight different areas in Northern and Central Italy were tested for HPV infection with Hybrid Capture 2 (HC2). Genotyping of the HC2-positive samples was performed for 13 HPV types targeted by GP5+/GP6+ PCR, followed by Reverse Line Blot. Logistic regression was used to model type-specific HPV positivity, adjusted for age, study area, and specific HPV type prevalence. Subject-level random effects were added to represent unobservable risk factors common to all HPV types. RESULTS: A total of 36,877 women were included. Of 2833 HC2-positive women, 2108 were confirmed to be positive for any of the 13 specific HPV infections using the PCR assay, and amongst them 430 (20.4% of all PCR-positive women) were infected with multiple types. The observed-to-expected ratio for infection with >=2 HPV types was 1.21 (95% Credible Interval: 1.13-1.30). Amongst the 78 combinations of specific HPV types, none of the pairs reached the chosen level of significance, p value <0.01. CONCLUSIONS: Multiple HPV infections occurred more frequently than predicted by chance. The excess of multiple infections was small, though not completely absent, after controlling for all sources of common correlation between HPV types. The present analysis of the NTCC screening study showed no evidence that specific HPV types have the tendency to be found more or less often than others in coinfections. PMID- 22088484 TI - A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group. AB - PURPOSE: To determine the toxicity, efficacy and pharmacokinetics of trabectedin given over 24h every 3 weeks to children with recurrent rhabdomyosarcoma, Ewing sarcoma, or non-rhabdomyosarcoma soft tissue sarcomas. PATIENTS AND METHODS: Trabectedin was administered as a 24-h intravenous infusion every 21 days. Two dose levels were evaluated (1.3 and 1.5mg/m(2)) for safety; efficacy was then evaluated using a traditional 2-stage design (10+10) at the 1.5mg/m(2) dose level. Pharmacokinetics (day 1 and steady state) were performed during cycle 1. RESULTS: Fifty patients were enrolled, eight patients at 1.3mg/m(2) and 42 at 1.5mg/m(2). Dose limiting toxicities (DLTs) in the dose finding component included fatigue and reversible GGT elevation in 1/6 evaluable patients at 1.3mg/m(2) and 0/5 at 1.5mg/m(2). Efficacy was evaluated in 42 patients enrolled at the 1.5mg/m(2) dose of whom 22% experienced reversible grade 3 or 4 toxicities that included AST, ALT, or GGT elevations, myelosuppression and deep venous thrombosis. One patient with rhabdomyosarcoma had a partial response and one patient each with rhabdomyosarcoma, spindle cell sarcoma and Ewing sarcoma had stable disease for 2, 3 and 15 cycles, respectively. CONCLUSION: Trabectedin is safe when administered over 24h at 1.5mg/m(2). Trabectedin did not demonstrate sufficient activity as a single agent for children with relapsed paediatric sarcomas. PMID- 22088485 TI - Targeted BIRC5 silencing using YM155 causes cell death in neuroblastoma cells with low ABCB1 expression. AB - The BIRC5 (Survivin) gene is located at chromosome 17q in the region that is frequently gained in high risk neuroblastoma. BIRC5 is strongly over expressed in neuroblastoma tumour samples, which correlates to a poor prognosis. We recently validated BIRC5 as a potential therapeutic target by showing that targeted knock down with shRNA's triggers an apoptotic response through mitotic catastrophe. We now tested YM155, a novel small molecule selective BIRC5 suppressant that is currently in phase I/II clinical trials. Drug response curves showed IC50 values in the low nM range (median: 35 nM, range: 0.5-> 10,000 nM) in a panel of 23 neuroblastoma cell lines and four TIC-lines, which resulted from an apoptotic response. Nine out of 23 cell lines were relatively resistant to YM155 with IC50 values > 200 nM, although in the same cells shRNA mediated knock down of BIRC5 caused massive apoptosis. Analysis of differentially expressed genes between five most sensitive and five most resistant cell lines using Affymetrix mRNA expression data revealed ABCB1 (MDR1) as the most predictive gene for resistance to YM155. Inhibition of the multi-drug resistance pump ABCB1 with cyclosporine or knockdown with shRNA prior to treatment with YM155 demonstrated that cell lines with ABCB1 expression became 27-695 times more sensitive to YM155 treatment. We conclude that most neuroblastoma cell lines are sensitive to YM155 in the low nM range and that resistant cells can be sensitised by ABCB1 inhibitors. Therefore YM155 is a promising novel compound for treatment of neuroblastoma with low ABCB1 expression. PMID- 22088486 TI - Coarctation of the aorta in the newborn. PMID- 22088487 TI - Forensic antiepileptic drug levels in autopsy cases of epilepsy. AB - A 1-year retrospective coroner-based forensic examination of causes of death among persons with a history of epilepsy was conducted at the Allegheny County Coroner's Office to evaluate the phenomenon of sudden unexplained/unexpected death in epilepsy (SUDEP), a diagnosis of exclusion. All cases at the Coroner's Office from January 1, 2001 through December 31, 2001, were examined. Review of a total of 1200 autopsied deaths revealed 12 cases with a past medical history of seizure disorder on the death certificate, which listed seizure disorder as the immediate cause of death or contributory cause of the death. Of the 7 men with seizure disorders, 5 were categorized as definite SUDEP and 2 as possible SUDEP. Of the 5 women with seizure disorders, 2 were listed as definite SUDEP, 2 as possible, and 1 as non-SUDEP because the convulsive seizures developed from a grade II glial tumor. Postmortem findings were evaluated for 11 cases; 1 body was decomposed. Toxicological screens were carried out on blood, bile, urine, and eye fluid for all 12. Antiepileptic drug (AED) levels detected in postmortem toxicological analysis were examined. AED levels were determined in 7 cases. Four of 7 had subtherapeutic AED levels, 2 had therapeutic levels, and only 1 victim of SUDEP had levels above the therapeutic range. Five cases had no detectable AED levels. AED levels at autopsy were either absent or subtherapeutic in 9 of 10 SUDEP cases, findings consistent with the likelihood of poor AED compliance. Subtherapeutic levels of AEDs may be a risk factor for SUDEP that could contribute to increased interictal and/or ictal epileptiform activity with associated autonomic dysfunction leading to disturbance of heart rate, heart rhythm, and/or blood pressure. PMID- 22088488 TI - Monkey to human comparative anatomy of the frontal lobe association tracts. AB - The greater expansion of the frontal lobes along the phylogeny scale has been interpreted as the signature of evolutionary changes underlying higher cognitive abilities in humans functions in humans. However, it is unknown how an increase in number of gyri, sulci and cortical areas in the frontal lobe have coincided with a parallel increase in connectivity. Here, using advanced tractography based on spherical deconvolution, we produced an atlas of human frontal association connections that we compared with axonal tracing studies of the monkey brain. We report several similarities between human and monkey in the cingulum, uncinate, superior longitudinal fasciculus, frontal aslant tract and orbito-polar tract. These similarities suggest to preserved functions across anthropoids. In addition, we found major differences in the arcuate fasciculus and the inferior fronto-occipital fasciculus. These differences indicate possible evolutionary changes in the connectional anatomy of the frontal lobes underlying unique human abilities. PMID- 22088489 TI - Global considerations in measuring effectiveness of advanced practice nurses. AB - Documentation of advanced practice nurses' (APNs) effectiveness globally is essential in developing educational programs and standards, regulations, titling, prescribing privileges, and scope and standards of practice. Based on the body of research on APN effectiveness to date, two major factors have emerged in developing future studies, (1) careful, deliberate choice of outcomes and (2) dose effects. The purpose of this paper is to review these measurement issues. Careful selection in choice of patient outcomes important to regional and national health care challenges is essential in developing studies to document APN effects on outcomes important to the country and region. It is equally important to consider the concept of dose effects of the APNs. Dose effects consist of 3 components: dose (number of APNs at the clinical practice site, region or country and amount of APN care in minutes or contacts); APN (education, expertise, and experience); and host and host response (organizational, governmental or patient and/or family receptiveness to APNs and to APN practice). Considering each component of the concept is essential in developing studies to examine APN effectiveness internationally. PMID- 22088490 TI - Influence of stimulus amplitude on unintended visuomotor entrainment. AB - Rhythmic limb movements have been shown to spontaneously coordinate with rhythmic environmental stimuli. Previous research has demonstrated how such entrainment depends on the difference between the movement periods of the limb and the stimulus, and on the degree to which the actor visually tracks the stimulus. Here we present an experiment that investigated how stimulus amplitude influences unintended visuomotor entrainment. Participants performed rhythmic forearm movements while visually tracking an oscillating stimulus. The amplitude and period of stimulus motion were manipulated. Larger stimulus amplitudes resulted in stronger entrainment irrespective of how participants visually tracked the movements of the stimulus. Visual tracking, however, did result in increased entrainment for large, but not small, stimulus amplitudes. Collectively, the results indicate that the movement amplitude of environmental stimuli plays a significant role in the emergence of unintended visuomotor entrainment. PMID- 22088491 TI - Clinical evaluation of acute systemic reaction and detection of IgG antibodies against PF4/heparin complexes in hemodialysis patients. AB - Heparin-induced thrombocytopenia (HIT) is a pathophysiological syndrome caused by platelet-activating antibodies that recognize PF4/heparin complexes. The abrupt onset of HIT following intravenous bolus heparin is known as an acute systemic reaction. Clinical features of this type of HIT may be similar to those of common complications during hemodialysis. The aim of the study was to identify whether the clinical features of the acute systemic reaction are caused by HIT or dialytic complications. Twenty-seven dialytic patients who had thrombocytopenia and clinical features of an acute systemic reaction were enrolled out of 202 HIT suspected patients. Thirteen patients had HIT confirmed due to the presence of positive functional and immunoassays. Eight of the thirteen patients presented with acute systemic reactions due to HIT. The most common symptom of acute systemic reaction was dyspnea. The other nineteen patients, involving both HIT and non-HIT patients, had dialysis-complicated ASR. The major feature of the acute systemic reaction in hemodialysis was hypotension and its relevant symptoms. An immunoassay for the detection of IgG antibodies against PF4/heparin complexes (HIT-IgG) showed the wide-range linearity of the calibration curve by employing three concentrations of recombinant mouse monoclonal antibodies for PF4/heparin complexes. The results are expressed as micrograms of IgG in one milliliter. Significantly high levels in thirteen HIT patients were compared with levels in fourteen non-HIT patients. The highest median of 1,530 MUg/ml (IQR: 3,267-813) was obtained in the presence of HIT associated with an acute systemic reaction. In HIT patients who did not show characteristics of an HIT-derived acute systemic reaction, the median was 339 MUg/ml (1,178-834). Despite showing a positive ELISA, nine non-HIT patients without any platelet-activating antibodies showed a value of 97 MUg/ml (166-56). The lowest median of 8.3 MUg/ml (11-6) was in non-HIT patients with a negative ELISA. In conclusion, measurements of HIT-IgG -specific antibodies can facilitate an appropriate estimation in hemodialysis patients of whether the clinical features of an acute systemic reaction are caused by HIT or dialytic complications. PMID- 22088492 TI - GhostNet marine debris survey in the Gulf of Alaska--satellite guidance and aircraft observations. AB - Marine debris, particularly debris that is composed of lost or abandoned fishing gear, is recognized as a serious threat to marine life, vessels, and coral reefs. The goal of the GhostNet project is the detection of derelict nets at sea through the use of weather and ocean models, drifting buoys and satellite imagery to locate convergent areas where nets are likely to collect, followed by airborne surveys with trained observers and remote sensing instruments to spot individual derelict nets. These components of GhostNet were first tested together in the field during a 14-day marine debris survey of the Gulf of Alaska in July and August 2003. Model, buoy, and satellite data were used in flight planning. A manned aircraft survey with visible and IR cameras and a LIDAR instrument located debris in the targeted locations, including 102 individual pieces of debris of anthropogenic or terrestrial origin. PMID- 22088493 TI - Analysis of the factor structure of the Sociocultural Attitudes Towards Appearance Questionnaire (SATAQ-3) in Spanish secondary-school students through exploratory structural equation modeling. AB - The aims of the present study were: (1) to assess the factor structure of the SATAQ-3 in Spanish secondary-school students by means of exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM) models; and (2) to study its invariance by sex and school grade. ESEM is a technique that has been proposed for the analysis of internal structure that overcomes some of the limitations of EFA and CFA. Participants were 1559 boys and girls in grades seventh to tenth. The results support the four-factor solution of the original version, and reveal that the best fit was obtained with ESEM, excluding Item 20 and with correlated uniqueness between reverse-keyed items. Our version shows invariance by sex and grade. The differences between scores of different groups are in the expected direction, and support the validity of the questionnaire. We recommend a version excluding Item 20 and without reverse-keyed items. PMID- 22088494 TI - Is adjunctive dexamethasone beneficial in patients with bacterial meningitis? PMID- 22088495 TI - Time patients spend in the emergency department: England's 4-hour rule-a case of hitting the target but missing the point? AB - STUDY OBJECTIVE: To address concerns about prolonged emergency department (ED) stays from crowding, England mandated that the maximum length of ED stay for 98% of patients be no greater than 4 hours. We evaluate the effect of the mandated ED care intervals in England. METHODS: This was a retrospective analysis of ED patient throughput before, during, and after implementation of the target. Fifteen acute hospital trusts' ED data were purposively sampled, including all patient visits during May and June of 2003 to 2006. We compared total time in ED and time to clinician across years, segregating for admitted versus discharged patients and young versus old patients, using a random-effects regression model and adjusting for hospital clustering. RESULTS: We analyzed 735,588 ED visits. The proportion of patients seen and treated within 4 hours improved from 83.9% to 96.3%. Adjusted total length of ED stay from 2003 to 2006 increased by 8.6 minutes for all patients and 30 minutes for admissions; time to physician improved by 1 minute for all patients. The proportion of patients leaving the ED during the last 20 minutes before 4 hours increased from 4.7% of all patients in 2003 to 8.4% in 2006. Admitted patients were more likely than discharged ones to leave the ED in the last 20 minutes, and the relative likelihood increased each year after 2003, with incidence rate ratio 1.04 (95% confidence interval [CI] 0.78 to 1.39), 1.39 (95% CI 1.05 to 1.82), and 1.55 (95% CI 1.19 to 2.20) for 2004, 2005, and 2006, respectively. An increasing proportion of elderly patients were in the last 20-minute departure interval each year compared with younger patients (in 2003 7.4% versus 4.1%; in 2006 17.3% versus 6.3%). CONCLUSION: The introduction of a time target reduced the proportion of patients staying greater than 4 hours. More patients departed within 20 minutes of the target 4-hour interval after the mandate, notably, the elderly. PMID- 22088496 TI - A new antifungal coumarin from Clausena excavata. AB - A new gamma-lactone coumarin, named as excavarin-A, showing antifungal activity was isolated from the leaves of Clausena excavata by bioassay guided fractionation method. The structure was elucidated by spectroscopic data analysis and identified as 7((2E)-4(4,5-dihydro-3-methylene-2-oxo-5-furanyl)-3-methylbut-2 enyloxy) coumarin. Minimum inhibitory concentration (MIC) was determined against fifteen fungal strains pathogenic against plants and human. The least MIC was recorded against the human pathogen, Candida tropicalis and the plant pathogens Rhizoctonia solani and Sclerotinia sclerotiorum. Antifungal activities against the human pathogens, Aspergillus fumigatus and Mucor circinelloides and plant pathogens, Colletotrichum gloeosporioides, Lasiodiplodia theobromae, Fusarium oxysporum and Rhizopus stolonifer were stronger than that of the standard antimicrobials. PMID- 22088497 TI - New antioxidant and antiglycation active triterpenoid saponins from the root bark of Aralia taibaiensis. AB - Four new oleanane type triterpenoid saponins (1-4) and a known saponin (5) were isolated from the root bark of Aralia taibaiensis Z.Z. Wang et H.C. Zheng. The structures of the four new compounds were elucidated as 3-O-{beta-D glucopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->3)]-beta-D-glucurono-pyranosyl} olean-11,13(18)-diene-28-oic acid 28-O-beta-D-glucopyranosyl ester (1), 3-O-{beta D-gluco-pyranosyl-(1->3)-[alpha-l-arabinofuranosyl-(1->4)]-beta-D glucuronopyranosyl}-olean-11,13(18)-diene-28-oic acid 28-O-beta-D-glucopyranosyl ester (2), 3-O-{beta-d-glucopyranosyl-(1->2)-[alpha-l-arabinofuranosyl-(1->4)] beta-D-glucuronopyranosyl}-oleanolic acid 28-O-beta-D-glucopyranosyl ester (3) and 3-O-{beta-D-glucopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->3)]-beta-D glucuronopyranosyl}-oleanolic acid 28-O-beta-D-glucopyranosyl ester (4), on the basis of extensive spectral analysis and chemical evidence. Compounds 1-5 exhibited moderate effects on antioxidant and antiglycation activities, which correlated with treatment of diabetes mellitus. PMID- 22088498 TI - Anthropogenic and natural sources of acidity and metals and their influence on the structure of stream food webs. AB - We compared food web structure in 20 streams with either anthropogenic or natural sources of acidity and metals or circumneutral water chemistry in New Zealand. Community and diet analysis indicated that mining streams receiving anthropogenic inputs of acidic and metal-rich drainage had much simpler food webs (fewer species, shorter food chains, less links) than those in naturally acidic, naturally high metal, and circumneutral streams. Food webs of naturally high metal streams were structurally similar to those in mining streams, lacking fish predators and having few species. Whereas, webs in naturally acidic streams differed very little from those in circumneutral streams due to strong similarities in community composition and diets of secondary and top consumers. The combined negative effects of acidity and metals on stream food webs are clear. However, elevated metal concentrations, regardless of source, appear to play a more important role than acidity in driving food web structure. PMID- 22088499 TI - Re: "Application of a repeat-measure biomarker measurement error model to 2 validation studies: examination of the effect of within-person variation in biomarker measurements". PMID- 22088500 TI - Effect of cerium dioxide, titanium dioxide, silver, and gold nanoparticles on the activity of microbial communities intended in wastewater treatment. AB - Growth in production and use of nanoparticles (NPs) will result increased concentrations of these in industrial and urban wastewaters and, consequently, in wastewater-treatment facilities. The effect of this increase on the performance of the wastewater-treatment process has not been studied systematically and including all the microbial communities involved in wastewater treatment. The present work investigates, by using respiration tests and biogas-production analysis, the inhibitory effect of four different commonly used metal oxide (CeO(2) and TiO(2)) and zero-valent metal (Ag and Au) nanoparticles on the activity of the most important microbial communities present in a modern wastewater-treatment plant. Specifically, the actions of ordinary heterotrophic organisms, ammonia oxidizing bacteria, and thermophilic and mesophilic anaerobic bacteria were tested in the presence and absence of the nanoparticles. In general, CeO(2) nanoparticles caused the greatest inhibition in biogas production (nearly 100%) and a strong inhibitory action of other biomasses; Ag nanoparticles caused an intermediate inhibition in biogas production (within 33-50%) and a slight inhibition in the action of other biomasses, and Au and TiO(2) nanoparticles caused only slight or no inhibition for all tested biomasses. PMID- 22088501 TI - Phosphate removal from wastewaters by a naturally occurring, calcium-rich sepiolite. AB - Developing an easily handled and cost-effective phosphate absorbent is crucial for the control of water eutrophication. In this study, a naturally occurring, calcium-rich sepiolite (NOCS) was evaluated for its feasibility as a phosphate absorbent candidate. Batch studies showed that phosphate sorption on NOCS followed a stepwise isotherm for concentrations between 5 and 1000 mg P/l, and the phosphate sorption was fitted well by the Freundlich equation. The estimated maximum phosphorus sorption capacity was 32.0 mg P/g, which was quite high compared with other natural materials and was comparable to some efficient manmade P absorbents. The NOCS sorption kinetics followed a pseudo-first-order model with an R(2) value of 0.999. The adsorption of phosphate was highly pH dependent. Phosphate adsorption decreased moderately with increasing pH values from 3.0 to 6.0, and it decreased sharply in alkaline conditions. Ionic strength, sulfate, nitrate and chloride anions had no effects on the phosphate removal capacity of NOCS, but fluoride and bicarbonate anions exerted large effects. Phosphorus fractionation indicated that phosphate removed from the solution was primarily formed as a calcium-bound phosphorus precipitation, which was further confirmed by SEM-EDS analysis. Moreover, phosphate was barely (<1.5%) desorbed from the phosphorus-adsorbed sepiolite regardless of pH value. PMID- 22088502 TI - Leaching characteristics of steel slag components and their application in cementitious property prediction. AB - High-efficiency recovery and utilization of steel slag are important concerns for environmental protection and sustainable development. To establish a rapid method to evaluate the cementitious properties of steel slag, leaching tests were carried out on steel slag components via an evaporation-condensation method; the leaching characteristics and mechanism of the slag were also investigated. The relationship between leaching characteristics and cementitious properties, which were represented by mortar compressive strength, was analyzed. Results show that there exist significant differences among the amounts of chemically active leached components. The leaching process can be described by the shrinking unreacted core model controlled by intra-particle diffusion, and is in accordance with Kondo R hydration kinetics equation. The leaching process showed a good linear relationship between the amounts of components leached from steel slag and the mortar compressive strength of cementitious materials prepared from reference cement and steel slag with mass ratios of 50:50 and 70:30. The compressive strengths of mortars subjected to 7, 28, and 90 days of curing can be accurately predicted by the sum of leached (CaO+Al(2)O(3)) obtained after a certain length of leaching time. PMID- 22088503 TI - Ionothermal synthesis of hierarchical BiOBr microspheres for water treatment. AB - Bismuth oxybromide (BiOBr) micropsheres with hierarchical morphologies have been fabricated via an ionothermal synthesis route. Ionic liquid acts as a unique soft material capable of promoting nucleation and in situ growth of 3D hierarchical BiOBr mesocrystals without the help of surfactants. The as-prepared BiOBr nanomaterials can effectively remove heavy metal ions and organic dyes from wastewater. They can also kill Micrococcus lylae, a Gram positive bacterium, in water under fluorescent light irradiation. Their high adaptability in water treatment may be ascribed to their hierarchical structure, allowing them high surface to volume ratio, facile species transportation and excellent light harvesting ability. PMID- 22088504 TI - Cytotoxicity of serum protein-adsorbed visible-light photocatalytic Ag/AgBr/TiO2 nanoparticles. AB - Photocytotoxicity of visible-light catalytic Ag/AgBr/TiO(2) nanoparticles (NPs) was examined both in vitro and in vivo. The Ag/AgBr/TiO(2) NPs were prepared by the deposition-precipitation method. Their crystalline structures, atomic compositions, and light absorption property were examined by X-ray diffraction (XRD) patterns, X-ray photoelectron (XPS) intensities, and ultraviolet-visible (UV-vis) diffuse reflectance spectroscopic tools. The Ag/AgBr/TiO(2) NPs appeared to be well internalized in human carcinoma cells as evidenced by transmission electron microscopy (TEM). The cytotoxicity of cetylmethylammonium bromide (CTAB) appeared to be significantly reduced by adsorption of serum proteins in the cellular medium on the NP surfaces. Two types of human cervical HeLa and skin A431 cancer cells were tested to check their viability after the cellular uptake of the Ag/AgBr/TiO(2) NPs and subsequent exposure to an illumination of visible light from a 60 W/cm(2) halogen lamp. Fluorescence images taken to label mitochondria activity suggest that the reactive oxygen species should trigger the photo-destruction of cancer cells. After applying the halogen light illumination for 50-250 min and ~8 ppm (MUg/mL) of photocatalytic Ag/AgBr/TiO(2) NPs, we observed a 40-60% selective decrease of cell viability. Ag/AgBr/TiO(2) NPs were found to eliminate xenograft tumors significantly by irradiating visible light in vivo for 10 min. PMID- 22088505 TI - Combining scanning tunneling microscopy and synchrotron radiation for high resolution imaging and spectroscopy with chemical, electronic, and magnetic contrast. AB - The combination of high-brilliance synchrotron radiation with scanning tunneling microscopy opens the path to high-resolution imaging with chemical, electronic, and magnetic contrast. Here, the design and experimental results of an in-situ synchrotron enhanced x-ray scanning tunneling microscope (SXSTM) system are presented. The system is designed to allow monochromatic synchrotron radiation to enter the chamber, illuminating the sample with x-ray radiation, while an insulator-coated tip (metallic tip apex open for tunneling, electron collection) is scanned over the surface. A unique feature of the SXSTM is the STM mount assembly, designed with a two free-flex pivot, providing an angular degree of freedom for the alignment of the tip and sample with respect to the incoming x ray beam. The system designed successfully demonstrates the ability to resolve atomic-scale corrugations. In addition, experiments with synchrotron x-ray radiation validate the SXSTM system as an accurate analysis technique for the study of local magnetic and chemical properties on sample surfaces. The SXSTM system's capabilities have the potential to broaden and deepen the general understanding of surface phenomena by adding elemental contrast to the high resolution of STM. PMID- 22088506 TI - Optimum HRTEM image contrast at 20 kV and 80 kV--exemplified by graphene. AB - The dependence of high-resolution transmission electron microscopy (HRTEM) image contrast of graphene on the adjustable parameters of an aberration-corrected microscope operated at 80 and 20 kV has been calculated and, for 80 kV, compared with measurements. We used density functional theory to determine the projected atom potential and obtained the image intensity by averaging over the energy distribution of the imaging electrons, as derived from the electron energy loss spectroscopy measurements. Optimum image contrast has been determined as a function of energy spread of the imaging electrons and chromatic aberration coefficient, showing that significant improvement of contrast can be achieved at 80 kV with the help of a monochromator, however at 20 kV only with chromatic aberration correction and bright atom contrast conditions. PMID- 22088507 TI - In-situ TEM on (de)hydrogenation of Pd at 0.5-4.5 bar hydrogen pressure and 20 400 degrees C. AB - We have developed a nanoreactor, sample holder and gas system for in-situ transmission electron microscopy (TEM) of hydrogen storage materials up to at least 4.5 bar. The MEMS-based nanoreactor has a microheater, two electron transparent windows and a gas inlet and outlet. The holder contains various O rings to have leak-tight connections with the nanoreactor. The system was tested with the (de)hydrogenation of Pd at pressures up to 4.5 bar. The Pd film consisted of islands being 15 nm thick and 50-500 nm wide. In electron diffraction mode we observed reproducibly a crystal lattice expansion and shrinkage owing to hydrogenation and dehydrogenation, respectively. In selected area electron diffraction and bright/dark-field modes the (de)hydrogenation of individual Pd particles was followed. Some Pd islands are consistently hydrogenated faster than others. When thermally cycled, thermal hysteresis of about 10-16 degrees C between hydrogen absorption and desorption was observed for hydrogen pressures of 0.5-4.5 bar. Experiments at 0.8 bar and 3.2 bar showed that the (de)hydrogenation temperature is not affected by the electron beam. This result shows that this is a fast method to investigate hydrogen storage materials with information at the nanometer scale. PMID- 22088508 TI - Imaging properties of bright-field and annular-dark-field scanning confocal electron microscopy: II. point spread function analysis. AB - The imaging properties of bright field and annular dark field scanning confocal electron microscopy (BF-SCEM and ADF-SCEM) are discussed based on their point spread functions (PSFs) in comparison with multislice simulations. Although the PSFs of BF-SCEM and ADF-SCEM show similar hourglass shapes, their numerical distributions are quite different: BF-SCEM PSF is always positive and shows a center of symmetry whereas the ADF-SCEM PSF is complex and has Hermitian symmetry. These PSF properties explain the large elongation effect in BF-SCEM for laterally extended object and almost no-elongation in ADF-SCEM, illustrating the importance of the numerical analysis of PSFs. The Hermitian symmetry of the ADF SCEM PSF results in an interesting "edge enhancement effect" at the interface. Simulation using the PSF and the multislice method verified this effect at GaAs surfaces and InAs interfaces embedded in GaAs. This unique feature of ADF-SCEM can potentially be useful for depth sectioning. It is also pointed out that a PSF imaging model cannot be applicable for BF-SCEM of a phase object, when the system is symmetric and aberration free. PMID- 22088509 TI - Towards improving the diagnosis and management of chronic cough in China. PMID- 22088510 TI - The Chinese national guidelines on diagnosis and management of cough (December 2010). PMID- 22088511 TI - Multiple dimensions of cardiopulmonary dyspnea. AB - BACKGROUND: The current theory of dyspnea perception presumes a multidimensional conception of dyspnea. However, its validity in patients with cardiopulmonary dyspnea has not been investigated. METHODS: A respiratory symptom checklist incorporating spontaneously reported descriptors of sensory experiences of breathing discomfort, affective aspects, and behavioral items was administered to 396 patients with asthma, chronic obstructive pulmonary disease (COPD), diffuse parenchymal lung disease, pulmonary vascular disease, chronic heart failure, and medically unexplained dyspnea. Symptom factors measuring different qualitative components of dyspnea were derived by a principal component analysis. The separation of patient groups was achieved by a variance analysis on symptom factors. RESULTS: Seven factors appeared to measure three dimensions of dyspnea: sensory (difficulty breathing and phase of respiration, depth and frequency of breathing, urge to breathe, wheeze), affective (chest tightness, anxiety), and behavioral (refraining from physical activity) dimensions. Difficulty breathing and phase of respiration occurred more often in COPD, followed by asthma (R(2) = 0.12). Urge to breathe was unique for patients with medically unexplained dyspnea (R(2) = 0.12). Wheeze occurred most frequently in asthma, followed by COPD and heart failure (R(2) = 0.17). Chest tightness was specifically linked to medically unexplained dyspnea and asthma (R(2) = 0.04). Anxiety characterized medically unexplained dyspnea (R(2) = 0.08). Refraining from physical activity appeared more often in heart failure, pulmonary vascular disease, and COPD (R(2) = 0.15). CONCLUSIONS: Three dimensions with seven qualitative components of dyspnea appeared in cardiopulmonary disease and the components under each dimension allowed separation of different patient groups. These findings may serve as a validation on the multiple dimensions of cardiopulmonary dyspnea. PMID- 22088512 TI - Diagnostic efficiency and complication rate of CT-guided lung biopsy: a single center experience of the procedures conducted over a 10-year period. AB - BACKGROUND: Computed tomography (CT)-guided transthoracic lung biopsy is a well established technique for the diagnosis of pulmonary lesions. The objective of this study was to evaluate the diagnostic efficiency and complication rate of CT guided lung biopsy in a Chinese population. METHODS: CT-guided cutting needle lung biopsies were performed in our institution on 1014 patients between January 2000 and October 2010. A chest radiograph was taken after the biopsy. Data about basic patient information, final diagnosis, and complications secondary to biopsy procedure (pneumothorax and bleeding) were extracted. RESULTS: The diagnostic efficiency of CT-guided lung biopsy was 94.8%; only 53 patients did not get a final diagnosis from lung biopsy. Final diagnoses found 639 malignant lesions (63.0%) and 322 benign lesions (31.8%). Pneumothorax occurred in 131 patients and 15 required insertion of an intercostal drain. Small hemoptysis occurred in 41 patients and mild parenchymal hemorrhage occurred in 16 patients. The overall complication rate was 18.5%. CONCLUSIONS: CT-guided cutting needle biopsy of pulmonary lesions is a relatively safe technique with a high diagnostic accuracy. It can be safely performed in clinical trials. PMID- 22088513 TI - Hemodynamic effects and safety of pulmonary angiography in Chinese patients with pulmonary hypertension. AB - BACKGROUND: Pulmonary angiography is widely performed in pulmonary hypertension patients, but its immediate effects on right heart hemodynamics and safety are not well known. The objective of this study was to investigate the right heart hemodynamic effects and safety of pulmonary angiography in Chinese patients with pulmonary hypertension. METHODS: Between January 2008 and June 2009, pulmonary hypertension patients undergoing pulmonary angiography were consecutively enrolled. Pulmonary angiography was performed during breath-holding after deep breathing. The baseline clinical data, hemodynamic measurements before and after pulmonary angiography and complications occurring within 48 hours after angiography were recorded. RESULTS: Ninety-five patients were included. All received non-ionic contrast medium with a volume of (75.7 +/- 29.8) ml. Angiography reduced heart rate in patients with baseline mean pulmonary arterial pressure >= 60 mmHg (change of heart rate: (-3.1 +/- 7.0) beats/min, P = 0.005), increased mean right atrial pressure, diastolic and end-diastolic right ventricular pressure in patients with baseline mean pulmonary arterial pressure < 60 mmHg (all P < 0.05). Patients with decreased mean pulmonary arterial pressure (change of mean pulmonary arterial pressure <= -10 mmHg) had the highest total pulmonary resistance (P = 0.009 vs. no change in mean pulmonary arterial pressure (change of mean pulmonary arterial pressure, -10 mmHg to 10 mmHg); P = 0.03 vs. increased mean pulmonary arterial pressure (change of mean pulmonary arterial pressure >= 10 mmHg)) and the lowest cardiac output (P = 0.018 vs. no change in mean pulmonary arterial pressure; P = 0.013 vs. increased mean pulmonary arterial pressure). There were 7 complications (7%), with 6 related to catheter and only 1 directly related to angiography. All complications were mild and no death occurred. CONCLUSION: Pulmonary angiography has minimal effect on right heart hemodynamics and is safe in pulmonary hypertension patients. PMID- 22088514 TI - XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer. AB - BACKGROUND: X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a new tumor suppressor. Low expression of XAF1 is associated with poor prognosis of human cancers. However, the effect of XAF1 on lung cancer remains unknown. In this study, we investigated the expression of XAF1 and its role in squamous cell lung cancer. METHODS: Cancer tissues, cancer adjacent tissues and normal lung tissues were collected from 51 cases of squamous cell lung cancer. The expression of XAF1 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expression of XAF1 protein was determined by Western blotting and immunohistochemical staining. Ad5/F35-XAF1 virus was generated. Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) method and flow cytometry (FACS), respectively. RESULTS: The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues (P < 0.05). The low expression of XAF1 was associated with tumor grade, disease stage, differentiation status and lymph node metastasis in squamous cell lung cancer patients. The restoration of XAF1 expression mediated by Ad5/F35-XAF1 virus significantly inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner. CONCLUSION: XAF1 is a valuable prognostic marker in squamous cell lung cancer and may be a potential candidate gene for lung cancer therapy. PMID- 22088515 TI - Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: a prospective study from China. AB - BACKGROUND: Early detection and diagnosis is urgent for the sake of effective treatment strategy for lung cancer. However, a convenient, economical and relatively precise method is not available. We here report a prospective study to find the possible value of the combined use of four popular tumor markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung. METHODS: Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumor group according to post-operative histological examinations. Serum levels of four tumor markers including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), Cyfra 21-1 and neuron specific enolase (NSE) were assayed for each patient. Receiver operating characteristic (ROC) curves were constructed for each tumor marker. The power of lung cancer diagnosis of each tumor marker, as well as a combination of them were analyzed and compared. RESULTS: The serum levels (median, range) of SCC, CEA, Cyfra 21-1 and NSE were 0.44 (0.01 - 35.70) ng/ml, 2.49 (0.30 - 26.78) ng/ml, 2.30 (0.82 - 73.33) ng/ml and 10.54 (0.10 - 56.41) ng/ml respectively in lung cancer group, and were 0.32 (0.01 - 0.90) ng/ml, 1.60 (0.20 - 8.93) ng/ml, 1.41 (0.72 - 4.82) ng/ml and 9.36 (6.56 - 24.24) ng/ml respectively in the benign pulmonary tumor group. The difference in each tumor marker between the two groups was significant (P < 0.05). The ROCs of SCC, CEA, Cyfra 21-1 and NSE were 0.702 (95%CI, 0.654 - 0.751), 0.611 (95%CI, 0.563 - 0.659), 0.650 (95%CI, 0.601 - 0.700) and 0.598 (95%CI, 0.542 - 0.654) respectively, indicating very low power of these four tumor markers. When a combination of SCC, CEA, Cyfra 21-1 and NSE were employed, the diagnosis power was strengthened. CONCLUSION: SCC, CEA, Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung, especially when they were assayed together for one patient. PMID- 22088516 TI - Pulmonary fungal infections after bone marrow transplantation: the value of high resolution computed tomography in predicting their etiology. AB - BACKGROUND: The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy. This study aimed to compare high resolution computed tomography (HRCT) findings of the pulmonary fungal infections to determine whether the etiology of various fungal infections could be diagnosed with HRCT. METHODS: Eighty-five cases were enrolled. According to the pathogens responsible for fungal infections, the patients were classified into three groups including invasive aspergillosis (n = 52), candidiasis (n = 19) and cryptococcosis (n = 14) groups. All the patients underwent HRCT scans. Two independent radiologists retrospectively analyzed the HRCT scans regarding CT patterns and distribution of lung abnormality. RESULTS: Most fungal infections in the three groups occurred in the neutropenic phase. There was no significant difference in the constituent ratio of fungal infections at different phases after bone marrow transplantation among the three groups. Agreement between the two observers for all the CT characteristics of fungal infections was excellent (k > 0.75). There was a significant difference in occurrence ratio of mass among the three groups (P = 0.02). Occurrence ratio of mass (43.3%, 13/30) in the group with invasive aspergillosis was higher than in each of other two groups (20.0%, 2/10; 14.3%, 1/7). There was no significant difference in other CT characteristics of nodules or masses; including number, margin, halo sign, cavitation and air-crescent sign. There was no significant difference in number, margin, air bronchogram and distribution of air-space consolidation. CONCLUSIONS: The HRCT appearance of various pulmonary fungal infections has a great deal of overlap and is nonspecific. Mass is more common in invasive aspergillosis, which is helpful to the diagnosis of invasive aspergillosis after bone marrow transplantation. PMID- 22088517 TI - Real world clinical performance of the zotarolimus eluting coronary stent system in Chinese patients: a prospective, multicenter registry study. AB - BACKGROUND: Early clinical trials with the Endeavor zotarolimus eluting stent (ZES) in western populations demonstrated low rates of target lesion revascularization with a favorable safety profile including low late stent thrombosis with up to 5 years of follow-up. The aim of this clinical registry study was to evaluate real world clinical performance of the ZES coronary system in Chinese patients. METHODS: The China Endeavor Registry is a prospective, multicenter registry assessing the safety of the ZES system in a real world patient population. It was conducted at 46 centers in China in routine treatment of patients with coronary artery stenosis, including patients with clinical characteristics or lesion types that are often excluded from randomized controlled trials. The registry included 2210 adult patients who underwent single vessel or multi-vessel percutaneous coronary intervention. The primary end point was the rate of major adverse cardiac events (MACE) at 12 months. RESULTS: The 12 month rate of MACE for all patients in the registry was 3.03%. Cardiac death or myocardial infarction rate was 1.28% and target lesion revascularization rate was 1.66%, non-target lesion target vessel revascularization (TVR) was 0.52%, TVR was 2.18%, and target vessel failure was 3.22%. There was only one case of emergent cardiac bypass surgery. The 12-month overall incidence of all Academic Research Consortium (ARC)-defined stent thrombosis was 0.43%. CONCLUSION: Mid-term results from the real-world China Endeavor Registry suggest that Endeavor ZES was safe and effective in Chinese patients. PMID- 22088518 TI - Duloxetine versus placebo in the treatment of patients with generalized anxiety disorder in China. AB - BACKGROUND: Duloxetine is approved for the treatment of generalized anxiety disorder (GAD) in the United States and elsewhere. This study aimed to assess the efficacy, tolerability, and safety of duloxetine in Chinese patients with GAD. METHODS: This 9-site study consisted of double-blind treatment for 15 weeks either with duloxetine 60 - 120 mg or with placebo. Patients with at least moderately severe GAD and a Sheehan Disability Scale (SDS) global functioning impairment total score >= 12 were included in this study. Patients who were randomly assigned to duloxetine received 60 mg for 7 weeks; at that point, for nonresponders the dose was increased to 120 mg for the remaining 8 weeks. The primary efficacy measure was mean change from baseline to endpoint on the Hospital Anxiety and Depression Scale-Anxiety subscale score (HADS-A). Secondary efficacy measures included the Hamilton Anxiety Rating Scale (HAMA), the SDS, and pain measures. Safety and tolerability were assessed. RESULTS: Baseline characteristics did not differ significantly between treatment groups. Mean age of the subjects (n = 210) was 37.6 years, 50.5% were female, and 74.3% completed the 15 weeks treatment. Patients treated with duloxetine had significantly greater improvement compared to placebo on the HADS-A (mean change -6.6 vs. -4.9, respectively, P = 0.022). Improvement in anxiety was greater with duloxetine treatment at 7 weeks and continued through 15 weeks for both the HADS-A and the HAMA total score (0.01 <= P < 0.05). Compared with placebo, duloxetine was also associated with greater improvement on most secondary measures, but not on the SDS global functioning score. Nausea, dizziness, and somnolence occurred significantly more frequently as treatment-emergent adverse events with duloxetine treatment compared with placebo treatment. CONCLUSIONS: Duloxetine 60 120 mg once daily is effective and well-tolerated for the treatment of patients with GAD in China. PMID- 22088519 TI - Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting. METHODS: This 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures. RESULTS: A total of 1447 children with ADHD (mean age (9.52 +/- 2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P < 0.001) improvement with OROS-MPH (mean: 6.95 +/- 2.71) versus the score at baseline (10.45 +/- 2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study. CONCLUSION: This open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice. PMID- 22088520 TI - Comparison of tirofiban combined with dalteparin or unfractionated heparin in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction patients. AB - BACKGROUND: Primary percutaneous coronary intervention (PCI) is the best treatment of choice for acute ST segment elevation myocardial infarction (STEMI). This study aimed to determine the clinical outcomes of tirofiban combined with the low molecular weight heparin (LMWH), dalteparin, in primary PCI patients with acute STEMI. METHODS: From February 2006 to July 2006, a total of 120 patients with STEMI treated with primary PCI were randomised to 2 groups: unfractionated heparin (UFH) with tirofiban (group I: 60 patients, (61.2 +/- 9.5) years), and dalteparin with tirofiban (group II: 60 patients, (60.5 +/- 10.1) years). Major adverse cardiac events (MACE) during hospitalization and at 4 years after PCI were examined. Bleeding complications during hospitalization were also examined. RESULTS: There were no significant differences in sex, mean age, risk factors, past history, inflammatory marker, or echocardiography between the 2 groups. In terms of the target vessel and vascular complexity, there were no significant differences between the 2 groups. During the first 7 days, emergent revascularization occurred only in 1 patient (1.7%) in group I. Acute myocardial infarction (AMI) occurred in 1 (1.7%) patient in group I and in 1 (1.7%) in group II. Three (5.0%) patients in group I and 1 (1.7%) in group II died. Total in hospital MACE during the first 7 days was 4 (6.7%) in group I and 2 (3.3%) in group II. Bleeding complications were observed in 10 patients (16.7%) in group I and in 4 patients (6.7%) in group II, however, the difference was not statistically significant. No significant intracranial bleeding was observed in either group. Four years after PCI, death occurred in 5 (8.3%) patients in group I and in 4 (6.7%) in group II. MACE occurred in 12 (20.0%) patients in group I and in 10 (16.7%) patients in group II. CONCLUSIONS: Dalteparin was effective and safe in primary PCI of STEMI patients and combined dalteparin with tirofiban was effective and safe without significant bleeding complications compared with UFH. Although there was no statistically significant difference, LMWH decreased the bleeding complications compared with UFH. PMID- 22088521 TI - Endovascular treatment of iliac vein compression syndrome. AB - BACKGROUND: Iliac vein compression syndrome (IVCS), the symptomatic compression of the left common iliac vein between the right common iliac artery and the vertebrae, is not an uncommon condition. The aim of this research was to retrospectively evaluate long-term outcome and the significance of endovascular treatment in patients with left IVCS. METHODS: Between January 1997 and September 2008, 296 patients received interventional therapy in the left common iliac vein. In the second stage, 170 cases underwent saphenous vein high ligation and stripping. Two hundred and thirty-one cases were followed up over a period of 6 to 120 months (average 46 months) and evaluated for symptom improvement with color ultrasound and ascending venography. RESULTS: The stenotic or occlusive segments of the left iliac vein were successfully dilated in 285 cases, of whom 272 received stent implantation therapy. Most of the patients achieved satisfactory results on discharge. During the follow-up period, varicose veins were alleviated in 98.7% of the patients, and leg swelling disappeared or was obviously relieved in 84% of cases. About 85% of leg ulcers completely healed. The total patency rate was 91.7% as evaluated with color ultrasound and 91.5% with ascending venography. CONCLUSIONS: Endovascular treatment of IVCS provides effective symptomatic improvement and good long-term patency in most patients. PMID- 22088522 TI - A diagnosis-based health economic analysis of postural orthostatic tachycardia syndrome in Chinese children. AB - BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a common clinical problem in children and adolescents. The previous diagnostic approach to POTS of children and adolescents is based on a series of tests to exclude all other causes, which is time and medical resource consuming. Recently, a new diagnostic approach has been developed. The present study was designed to statistically analyze the results of clinical investigation items and the cost for the diagnosis of POTS in children patients, and evaluate cost changes in the diagnosis of POTS. METHODS: A total of 315 children patients were divided into two groups according to diagnosis period, including group I diagnosed in 2002 - 2006 (100 cases) and group II in 2007 - 2010 (215 cases) and the diagnostic item based distribution of the cost was analyzed. The diagnostic costs were compared between two groups using SPSS17.0. RESULTS: The per-capita cost of diagnosis in group I was (621.95 +/- 21.10) Yuan, costs of diagnostic tests (head-up tilt test, standing test, etc) accounted for 8.68% and the exclusive tests for 91.32%. The per-capita cost of diagnosis in group II was (542.69 +/- 23.14) Yuan, diagnostic tests accounted for 10.50% and exclusive tests for 89.50%. Comparison of the total cost of diagnostic tests between the two groups showed significant differences (P < 0.05). CONCLUSION: The cost of POTS diagnosis has been declined in recent years, but the cost of exclusive diagnosis is still its major part. PMID- 22088523 TI - Endovascular treatment of Budd-Chiari syndrome. AB - BACKGROUND: Budd-Chiari syndrome (BCS) is a posthepatic portal hypertension caused by the obstruction of the lumen of the hepatic veins or the proximal inferior vena cava (IVC). This study aimed to evaluate the clinical experience of interventional therapy for Budd-Chiari syndrome. METHODS: IVC venography was carried out first, the obliteration or stenosis in the IVC was opened or dilated with the hard guided wire or Rups100 puncture needle and balloon, then a stent was routinely implanted for the type of obliteration or stenosis. RESULTS: The procedure was successful in 821 out of 903 cases including IVC intervention in 760 cases, and hepatic vein intervention in 61 cases. An IVC stent was used in 517 cases and hepatic vein stent in 19 cases. There were no pulmonary embolisms, but acute renal failure occurred in eight cases, hepatic coma in two cases and acute heart failure in 43 cases. Two patients died in this group and five cases were complicated with acute IVC thrombosis. Follow up of 7 to 124 months was made in 679 cases with recurrence found in 59 cases. CONCLUSIONS: Interventional therapy is safe and effective with a fast recovery for most types of BCS. It is gradually becoming the first therapeutic choice. PMID- 22088524 TI - Minimally invasive video-assisted thyroidectomy for accidental papillary thyroid microcarcinoma: comparison with conventional open thyroidectomy with 5 years follow-up. AB - BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT) has received increasing attention for malignant thyroid diseases. The aim of this study was to compare the outcomes of MIVAT with conventional open thyroidectomy (CT) for papillary thyroid microcarcinoma (PTMC). METHODS: Thirty-one patients were treated with MIVAT and 37 with CT. Their pathological characteristics, surgical complications, 5-year postoperative thyroglobulin (TG) and ultrasonic results were followed up. RESULTS: All the patients took levothyroxine for suppressing thyroid stimulating hormone (TSH) after surgery, and were followed up with measurement of serum TG and neck ultrasonography at intervals of 6 or 12 months. There was no statistically significant difference between the CT and MIVAT groups for sex ratio, operation time, positive lymph nodes, complications and prognosis, but the MIVAT group had better cosmetic results. CONCLUSIONS: MIVAT did not differ significantly from CT for PTMC after 5 years follow-up, but it did have better cosmetic results. MIVAT is a safe and valid surgical technique for selected cases. PMID- 22088525 TI - Short-term effects of supplementary feeding with enteral nutrition via jejunostomy catheter on post-gastrectomy gastric cancer patients. AB - BACKGROUND: Most gastric cancer patients who undergo gastrectomy develop malnutrition. It is, therefore, crucial to establish an effective means to provide nutrition for these patients. To perform home enteral nutrition (EN) to ensure adequate nutritional intake in gastric cancer patients, we placed a jejunostomy catheter during gastric surgery. Most patients showed improved nutritional status. METHODS: Twenty-nine inpatients at our hospital underwent radical gastrectomy and jejunostomy from December 2002 to December 2007 and were designated as the jejunostomy group, and 32 matched patients without a jejunostomy tube were designated as the tube-free group. The jejunostomy group was treated with EN from 72 hours to 3 months postoperatively. The tube-free group did not receive EN. Data including preoperative and postoperative body weight, body mass index (BMI), nutrition risk screening (NRS) score, Karnofsky performance score (KPS), and laboratory biochemical indicators were documented respectively and compared. RESULTS: Compared with preoperative week 1, both groups showed decreased body weight and BMI at 3 months postoperatively. The weight loss in the jejunostomy group ((7.1 +/- 3.3) kg) was significantly less than that in the tube-free group ((9.9 +/- 3.1) kg). Similarly, BMI decreased by (2.4 +/- 1.0) kg/m(2) in the jejunostomy group, which was significantly less than in the tube-free group ((3.2 +/- 0.9) kg/m(2)). The number of patients with postoperative NRS >= 3 was decreased in the jejunostomy group, but was increased in the tube-free group, and this difference was significant. There were no significant differences between the two groups in total lymphocyte count, hemoglobin, albumin and prealbumin, and adverse drug effects. CONCLUSIONS: Short term (3 months) EN supplementation via jejunostomy tube can reduce the risk of malnutrition and weight loss, and improve tolerance of chemotherapy. Tube feeding is reliable for achieving these goals because it is not important whether or not the patients have appetites. PMID- 22088526 TI - Intraoperative ultrasound assistance in the resection of small, deep-seated, or ill-defined intracerebral lesions. AB - BACKGROUND: Intraoperative ultrasound (IOUS) has been increasingly used as a guiding tool during neurosurgical procedures. In this study, we aimed to evaluate the potential application of intraoperative ultrasound assisted surgery in the resection of small, deep-seated, or ill-defined lesions. METHODS: Eighty-six consecutive patients with small, deep-seated, or ill-defined intracerebral lesions were studied prospectively. An improved intraoperative imaging technique and surgical setup were practiced during the surgery. IOUS was performed in three orthogonal imaging planes (horizontal, coronal and sagittal). RESULTS: Histopathological diagnoses of these 86 cases included cavernomas, metastases, hemangioblastomas, gliomas, and radiation necrosis. Forty-seven of the 86 lesions (54.7%) were small and deep-seated, 34/86 (39.5%) were ill-defined, and 5/86 (5.8%) were small, deep-seated, and ill-defined. Sonograms in the horizontal plane were obtained in all 86 cases. Sonograms in the sagittal plane and in the coronal plane were obtained only in 52 cases and in 46 cases, respectively, due to technical limitation. In 13 cases, sonograms in all three orthogonal planes were available. All lesions were successfully identified and localized by IOUS. Total resection was performed in 67 lesions (77.9%) and partial resection was performed in 19 lesions (22.1%). CONCLUSIONS: We propose IOUS to be performed in three orthogonal planes when surgery is planned for small, deep-seated, or ill defined brain lesions. By applying this simple, improved technique, surgeons can perform resection of these lesions precisely. PMID- 22088527 TI - Unplanned decannulation of tracheotomy tube in massive burn patients: a retrospective case series study. AB - BACKGROUND: Unplanned extubation is associated with adverse outcomes in intensive care unit. The massive burn patient differs from other critically ill patients in many ways. However, little is known about the unplanned decannulation (UD) in Burn Intensive Care Unit. This paper describes the special features of the circumstances and outcome of UD of tracheotomy tube in massive burn patients. METHODS: A case series study was performed between January 1999 and December 2008 and UD of tracheotomy tube was analyzed retrospectively. A total of 21 patients with 29 UD events were identified. Demographic data, diagnosis, intervention, UD events and outcome of UD patients were collected. Differences in proportions were compared using the chi-square (chi(2)) or Fisher's exact test. RESULTS: Patients with UD were often burned with head and neck (67%) and combined with inhalation injury (62%). The majority of them (76%) were transferred patients, occurred early (55%) and were accidental UD (79%). UD events tended to happen in day shift (90%) and to be associated with the medical procedure that was performing by caregivers at besides (79%). Loose of the stabilizing rope, medical procedure and tracheotomy malposition were the main causes of UD. Early UD and reintubation failure were associated with patients' death. CONCLUSIONS: UD happened to massive burn patients can lead to patient death. Careful management of respiratory tract was essential for massive burn patients. PMID- 22088528 TI - Ten-year survey on oncology publications from China and other top-ranking countries. AB - BACKGROUND: Cancer is a global disease that knows no borders. Over the past decade, oncology research had developed rapidly worldwide. The aim of this study was to evaluate the publication characteristics in oncology journals from China and other top-ranking countries. METHODS: The present study was designed to study publication characteristics in oncology journals from China and other top-ranking countries, the United States (USA), Japan, Germany, the United Kingdom (UK) and France, from 2001 to 2010. We also examined the research output from the three different regions of China: the mainland of China, Hong Kong and Taiwan. RESULTS: Articles published in 163 journals related to oncology were retrieved from the PubMed database. The number of articles showed significantly positive trends for the six countries. The percentage of articles in the world output showed a significantly positive increase in contributions from China, especially the mainland of China. China contributed 4.5% of the total 163 journals, and 2.5% of the journals with the top 10% impact factor (IF) scores. USA contributed 31.4% of the total world output, 40.5% of the top 10% IF score journals and ranked the first. CONCLUSIONS: This analysis described the research output from each country and region of China, and revealed the positive trend in China during 2001 and 2010. Also, by contrast with other top-ranking countries, these results imply that China falls behind the others in conducting high-quality oncology research. PMID- 22088529 TI - Health insurance and household income associated with mammography utilization among American women, 2000 - 2008. AB - BACKGROUND: National Breast and Cervical Cancer Early Detection Program (NBCCEDP) has provided free or low-cost mammograms to low-income or no health insurance women in all of the states of the United States (US) since 1997. The objective of this study was to understand whether health insurance and annual household income impacted the mammography utilization since the implementation of NBCCEDP, in order to evaluate how the implementation of NBCCEDP impacted mammography utilization among American women. METHODS: Data were from the database of Behavioral Risk Factor Surveillance System (BRFSS) of the CDC in US. Mammography utilization was measured by whether the American woman aged 40 to 64 years had the mammography within the last two years. The chi square test and multivariate Logistic regression were used to evaluate the associations between mammography utilization and health insurance, annual household income, and other factors for any given year. RESULTS: From 2000 to 2008, the rate of mammography utilization among participants had a steady decrease on the whole from 86.7% to 83.8%. The results showed that the mammography utilization correlated significantly with health insurance and annual household income for any given year. The results also showed that compared with participants who were uninsured, those who were insured had a greater times higher rate of mammography in 2008 than any other year from 2000 to 2008, and compared with participants whose annual household income was below $15 000, those whose annual household income was above $50 000 had a greater times higher rate of mammography in 2008 than in 2004 and 2006. CONCLUSIONS: Health insurance and annual household income impacted the mammography utilization for any given year from 2000 to 2008, and the implementation of NBCCEDP has not achieved its original goal on breast cancer screening. PMID- 22088530 TI - Role of extracellular signal-regulated kinase 1/2 in cigarette smoke-induced mucus hypersecretion in a rat model. AB - BACKGROUND: Airway mucus hypersecretion is an important pathophysiological feature of chronic obstructive pulmonary disease, which is closely associated with cigarette smoking. However, the signal transduction pathway from the cell surface to the nucleus through which cigarette smoke causes upregulation of mucin gene expression is not well known. This study was designed to investigate the role of extracellular signal-regulated Kinase 1/2 (ERK 1/2) in airway mucus hypersecretion induced by cigarette smoke in rats. METHODS: A rat model of airway mucus hypersecretion was induced by exposure to cigarette smoke for 4 weeks.Rats exposed to inhalation of cigarette smoke or normal saline were given an intraperitoneal injection of U0126, a specific MEK1 kinase inhibitor, at doses of 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg for 14 days. Expression of MUC5AC mRNA and protein, ERK 1/2 and phosphorylated-ERK 1/2 (p-ERK 1/2) were detected by RT-PCR, immunohistochemistry and Western blotting. RESULTS: Cigarette smoke significantly increased airway goblet cells metaplasia, induced the overexpression of MUC5AC mRNA and protein in bronchial epithelia, and increased the ratio of p-ERK 1/2 and ERK 1/2. U0126 significantly attentuated the expression of MUC5AC mRNA and protein induced by cigarette smoke (P < 0.05). Moreover, there was a significant positive correlation between the ratio of p-ERK1/2 to ERK1/2 and the expression of MUC5AC mRNA and protein (P < 0.05). CONCLUSIONS: Inhibition of ERK 1/2 by U0126 decreased the ratio of p-ERK 1/2 to ERK 1/2 and expression of MUC5AC mRNA and protein. ERK 1/2 may play an essential role in cigarette smoke-induced mucus hypersecretion in vivo. PMID- 22088531 TI - Calcineurin is involved in cardioprotection induced by ischemic postconditioning through attenuating endoplasmic reticulum stress. AB - BACKGROUND: Ischemic postconditioning (I-postC) is a newly discovered and more amenable cardioprotective strategy capable of protecting the myocardium from ischemia/reperfusion (I/R) injury. Endoplasmic reticulum (ER) is a principal site for secretary protein synthesis and calcium storage. Myocardial I/R causes ER stress and emerging studies suggest that the cardioprotection has been linked to the modulation of ER stress. The aim of the present study was to determine whether cardioprotection of I-postC involves reduction in ER stress through calcineurin pathway. METHODS: In the in vivo model of rat myocardial I/R, myocardial infarct size was measured by triphenyltetrazolium chloride (TTC) staining and apoptosis was detected using terminal eoxynucleotidyl transferase mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Expression of calreticulin, C/EBP homologous protein (CHOP), caspase-12, and activation of caspase-12 in myocardium were detected by Western blotting. The activity and expression of calcineurin in myocardium were also detected. RESULTS: I-postC protected the I/R heart against apoptosis, myocardial infarction, and leakage of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB). I-postC suppressed I/R-induced ER stress, as shown by a decrease in the expression of calreticulin and CHOP, and caspase-12 activation. I-postC downregulated calcineurin activation in myocardium subjected to I/R. CONCLUSION: I-postC protects myocardium from I/R injury by suppressing ER stress and calcineurin pathways are not associated with the I-postC-induced suppression of ER stress-related apoptosis. PMID- 22088532 TI - GRP78 upregulation-induced increase in cisplatin sensitivity of SPCA1 lung cancer cells. AB - BACKGROUND: Glucose regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone, plays a critical role in chemotherapy resistance in a variety of cancers. In this study, we investigated the up-regulation of GRP78 induced by A23187 and its association with the chemotherapeutical sensibility to cisplatin in human lung cancer cell line SPCA1. METHODS: SPCA1 cells were pretreated with A23187 at different concentrations. The expression of GRP78 at the mRNA level was analyzed by RT-PCR; the expression of GRP78 at the protein level was determined by Western blotting and immunofluorescence assay. Cell survival was determined by MTT assay. Cell apoptosis was analyzed by flow cytometry. RESULTS: The expression of GRP78 at both the mRNA and protein levels was obviously induced by A23187 in SPCA1 cells, with an elevation of GRP78 by 2.1-fold at the mRNA level and by 3.8 fold at the protein level compared to the control. There was a dose-dependent response. Survival curve analysis demonstrated that A23187 induction caused a significant reduction of survival for the cells subjected to cisplatin treatment (P < 0.05). After treatment by cisplatin, the percentage of apoptotic cells in the A23187 pretreated group increased about three fold compared with the control group ((27.53 +/- 4.32)% vs. (9.25 +/- 3.64)%, P < 0.05). CONCLUSIONS: A23187 treatment was fairly effective for the induction of GRP78 in SPCA1 cells at both the mRNA and protein levels. To a certain extent, GRP78 up-regulation by A23187 was associated with the enhancement of drug sensitivity to cisplatin in human lung cancer cell line SPCA1. PMID- 22088533 TI - Analysis of the ratio of mitchondrial DNA with A1555G mutant to wild type in deaf patients of Fujian province in China by a new method and its relationship with the severity of hearing loss. AB - BACKGROUND: It has been suggested that the ratio of mutant and wild type mitochondrial DNA may be related to its clinical phenotype. In this study, we developed a high sensitive real-time amplification refractory mutation system quantitative polymerase chain reaction (RT-ARMS-qPCR) assay for quantitation of the mitochondrial DNA (mtDNA) with a mutated 1555 site, and explored the relationship between the ratio of mutated mtDNA and the severity of hearing loss of mitochondrial deafness (MD) patients of Fujian province in China. METHODS: An amplified mtDNA fragment containing the 1555 site was ligated into a vector to construct a plasmid DNA standard. An RT-ARMS-qPCR system was used to measure the mtDNA copy number containing wild-type and mutant sequences in a cohort of 126 MD patients of Fujian province in China. Combined with the clinical data, we explored the relationship between the ratio of mutated mtDNA and the severity of hearing loss of MD. RESULTS: The variation coefficient in the cohort was 1.21%, the interassay variation coefficient was 1.78%, and the linear range was 10(2) - 10(8) copies/ul for detecting a recombinant, wild-type plasmid. The primers amplified only the intended sequences. Mutation copy number correlated with the degree of deafness in sporadic cases with heteroplasmic mutations of mtDNA A1555G (R = 0.811, P = 0.003), but not in sporadic cases with homoplasmic mutations (R = 0.007, P = 0.989). The copy number of homoplasmic or heteroplasmic mutations of mtDNA A1555G in familial cases correlated with degree of deafness (R = 0.352, P = 0.023 and R = 0.90, P = 0.012, respectively). CONCLUSIONS: The RT-ARMS-qPCR system is suitable for determining the copy number of mtDNA fragments containing the A1555G mutation. The ratio of mutated mtDNA correlates with the severity of hearing loss of MD. PMID- 22088534 TI - Clinical utility of automated platelet clump count in the screening for ethylene diamine tetraacetic acid-dependent pseudothrombocytopenia. AB - BACKGROUND: Platelet (PLT) clumping occurring in pseudothrombocytopenia (PTCP) can result in inaccurate PLT. Automated platelet clump count (APCC) is a quantitative parameter of platelet aggregation. In this study, we evaluated the clinical utility of APCC in the screening for platelet aggregation related ethylene diamine tetraacetic acid (EDTA)-dependent PTCP (EDTA-PTCP). METHODS: A total of 105 patients and 200 healthy individuals were enrolled in this study. Blood samples were collected with dipotassium EDTA and sodium citrate respectively. ADVIA 2120 hematology analyzer was used to perform complete blood count (CBC) and APCC. Blood smears of both EDTA- and citrate-anticoagulated samples were made for microscope observation and manual PLT counting. RESULTS: In 25 patients with EDTA-PTCP patients, for EDTA-2K anticoagulated-blood, PLT was (55 +/- 6) * 10(9)/L, significantly lower than citrate anticoagulated blood ((186 +/- 13) * 10(9)/L)). APCC was (905 +/- 694) * 10(9)/L, significantly higher than citrate anticoagulated blood (98 +/- 37) * 10(9)/L. In true thrombocytopenia and healthy control groups, APCC was (63 +/- 60) * 10(9)/L and (69 +/- 59) * 10(9)/L respectively and there was no significant difference between EDTA and citrate anticoagulants. Receiver operator characteristic (ROC) curve showed both sensitivity and specificity of APCC were 96% when the cutoff value of APCC was set as 182 * 10(9)/L. Other platelet parameters had poor performance. CONCLUSION: The APCC has a good sensitivity and specificity in differentiating EDTA-PTCP from true thrombocytopenia compared with other platelet parameters. PMID- 22088535 TI - A novel missense mutation of the TYR gene in a pedigree with oculocutaneous albinism type 1 from China. AB - BACKGROUND: The mutation of the tyrosinase (TYR) gene results in oculocutaneous albinism type 1 (OCA1), an autosomal recessive genetic disorder. OCA1 is the most common type of OCA in the Chinese population. Hence, the TYR gene was tested in this study. We also delineated the genetic analysis of OCA1 in a Chinese family. METHODS: Genomic DNA was isolated from the blood leukocytes of a proband and his family. Mutational analysis at the TYR locus by DNA sequencing was used to screen five exons, including the intron/exon junctions. A pedigree chart was drawn and the fundus of the eyes of the proband was also examined. RESULTS: A novel missense mutation p.I151S on exon 1, and homozygous TYR mutant alleles were identified in the proband. None of the mutants was identified among the 100 normal control subjects. Genetic analysis of the proband's wife showed normal alleles in the TYR gene. Thus, the fetus was predicated a carrier of OCA1 with a normal appearance. CONCLUSION: This study provided new information about a novel mutation, p.I151S, in the TYR gene in a Chinese family with OCA1. Further investigation of the proband would be helpful to determine the effects of this mutation on TYR activity. PMID- 22088536 TI - Effects of extremely low frequency magnetic field on anxiety level and spatial memory of adult rats. AB - BACKGROUND: As the widespread use of electric devices in modern life, human are exposed to extremely low frequency magnetic fields (ELF MF) much more frequently than ever. Over the past decades, a substantial number of epidemiological and experimental studies have demonstrated that ELF MF (50 Hz) exposure is associated with increased risk of various health effects. The present study examined the effects of chronic exposure to ELF MF on anxiety level and spatial memory of adult rats. METHODS: The 50-Hz ELF MF was used during the whole experimental procedures and the value of magnetic field (MF) was set to 2 mT. Adult rats were divided randomly to control, MF 1 hour and MF 4 hours group. Anxiety-related behaviors were examined in the open field test and the elevated plus maze; changes in spatial learning and memory were determined in Morris water maze after 4 weeks of daily exposure. RESULTS: Rats in MF 4 hours group had increased anxiety-like behaviors with unaltered locomotor activity. In the Morris water maze test, rats had reduced latency to find the hidden platform and improved long term memory of former location of platform without changes in short-term memory and locomotor activity. CONCLUSION: Chronic ELF MF exposure has anxiogenic effect on rats, and the promoting effects on spatial learning and long-term retention of spatial memory. PMID- 22088537 TI - Activation of c-Jun N-terminal kinase 1/2 regulated by nitric oxide is associated with neuronal survival in hippocampal neurons in a rat model of ischemia. AB - BACKGROUND: C-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in cerebral ischemia. Although the mechanistic basis for this activation of JNK1/2 is uncertain, oxidative stress may play a role. The purpose of this study was to investigate whether the activation of JNK1/2 is associated with the production of endogenous nitric oxide (NO). METHODS: Ischemia and reperfusion (I/R) was induced by cerebral four-vessel occlusion. Sprague-Dawley (SD) rats were divided into 6 groups: sham group, I/R group, neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole, 7-NI) given group, inducible nitric oxide synthase (iNOS) inhibitor (2-amino-5,6-dihydro-methylthiazine, AMT) given group, sodium chloride control group, and 1% dimethyl sulfoxide (DMSO) control group. The levels of protein expression and phospho-JNK1/2 were detected by Western blotting and the survival hippocampus neurons in CA1 zone were observed by cresyl violet staining. RESULTS: The study illustrated two peaks of JNK1/2 activation occurred at 30 minutes and 3 days during reperfusion. 7-NI inhibited JNK1/2 activation during the early reperfusion, whereas AMT preferably attenuated JNK1/2 activation during the later reperfusion. Administration of 7-NI and AMT can decrease I/R-induced neuronal loss in hippocampal CA1 region. CONCLUSION: JNK1/2 activation is associated with endogenous NO in response to ischemic insult. PMID- 22088538 TI - Nicotinamide mononucleotide adenylyltransferase 1 gene NMNAT1 regulates neuronal dendrite and axon morphogenesis in vitro. AB - BACKGROUND: Wallerian degeneration is a self-destructive process of axonal degeneration that occurs after an axonal injury or during neurodegenerative disorders such as Parkinson's or Alzheimer's disease. Recent studies have found that the activity of the nicotinamide adenine dinucleotide (NAD) synthase enzyme, nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) can affect the rate of Wallerian degeneration in mice and drosophila. NMNAT1 protects neurons and axons from degeneration. However, the role of NMNAT1 in neurons of central nervous system is still not well understood. METHODS: We set up the culture of primary mouse neurons in vitro and manipulated the expression level of NMNAT1 by RNA interference and gene overexpression methods. Using electroporation transfection we can up-regulate or down-regulate NMNAT1 in cultured mouse dendrites and axons and study the neuronal morphogenesis by immunocytochemistry. In all functional assays, FK-866 (CAS 658084-64-1), a highly specific non-competitive inhibitor of nicotinamide phosphoribosyltransferase was used as a pharmacological and positive control. RESULTS: Our results showed that knocking down NMNAT1 by RNA interference led to a marked decrease in dendrite outgrowth and branching and a significant decrease in axon growth and branching in developing cortical neurons in vitro. CONCLUSIONS: These findings reveal a novel role for NMNAT1 in the morphogenesis of developing cortical neurons, which indicate that the loss of function of NMNAT1 may contribute to different neurodegenerative disorders in central nervous system. PMID- 22088539 TI - Hemo oxygenase-1 induction in vitro and in vivo can yield pancreas islet xenograft survival and improve islet function. AB - BACKGROUND: The induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction. METHODS: Islet xenografts treated with CoPP-induction and CoPP + Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL-10) and IL-1beta level in serum and their mRNA and HO-1 mRNA and protein expression were examined. RESULTS: Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 (mRNA: 3.33- and 76.09-fold in vitro and in vivo; protein: 2.85- and 58.72-fold). The normoglycemia time in induction groups ((14.63 +/- 1.19) and (16.88 +/- 1.64) days) was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher. CONCLUSIONS: The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10. PMID- 22088540 TI - Microwave ablation: results in ex vivo and in vivo porcine livers with 2450-MHz cooled-shaft antenna. AB - BACKGROUND: Imaging-guided thermal ablation using different energy sources continues to gain favor as a minimally invasive technique for the treatment of primary and metastatic hepatic malignant tumors. This study aimed to evaluate the performance of microwave ablation with 2450-MHz internally cooled-shaft antenna in ex vivo and in vivo porcine livers. METHODS: All studies were animal care and ethics committee approved. Microwave ablation was performed using a noncooled or cooled-shaft antenna in 23 ex vivo (92 ablations) and eight in vivo (36 ablations) porcine livers. Diameters of the coagulation zone were observed on gross specimens. The coagulation diameters achieved in different microwave ablation parameter groups were compared. Curve estimation analysis was performed to characterize the relationship between applied power and treatment duration and coagulation diameter (including short-axis and long-axis diameter). RESULTS: Coagulation zones were elliptical and an arrowed-shaped carbonization zone around the shaft was observed in all groups. But the antenna track was also coagulated in the noncooled-shaft antenna groups. In ex vivo livers, the short-axis diameter correlated with the power output in a quadratic curve fashion (R(2) = 0.95) by fixing ablation duration to 10 minutes, and correlated with the ablation duration in a logarithmic curve fashion (R(2) = 0.98) by fixing power output to 80 W. The short-axis reached a relative plateau within 25 minutes. In in vivo livers, short axis diameter correlated with the coagulation duration in a sigmoidal curve fashion (60 W group R(2) = 0.76, 80 W group R(2) = 0.87), with a relative plateau achieved within 10 minutes for power settings of 60 W and 80 W. CONCLUSIONS: The internally cooled microwave antenna may be advantageous to minimize collateral damage. The short-axis diameter enlargement has a plateau by fixing power output. PMID- 22088541 TI - Co-culture with microglia promotes neural stem cells differentiation into astrocytes. AB - BACKGROUND: Neural stem cells (NSCs) are a self-renewing and multipotent population of the central nervous system (CNS), which are active during development and maintain homeostasis and tissue integrity throughout life. Microglias are an immune cell population resident in the CNS, which have crucial physiological functions in the developing and adult CNS. This study aimed to investigate that whether microglia co-cultured with NSCs could promote astrogliogenesis from NSCs. METHODS: Microglia and NSCs were co-cultured in 24 well insert plates. NSCs were plated in the bottom of the well and microglia in the insert. Fluorescent staining, Western blotting and RT-PCR were used to determine the effect of microglia on NSCs differentiation. RESULTS: Co-culture of microglia and NSCs promoted astrogliogenesis from NSCs. Several key genes, such as Notch 1, Notch 2, Notch 3, Hes 5, and NRSF were downregulated, while the critical genes Id1 and Id2 were upregulated. BMP2 and FGF2 were upregulated. CONCLUSION: Microglias act as a regulator of NSCs astrogliogenesis. PMID- 22088542 TI - Influenza A pandemic (H1N1) 2009 virus infection. AB - The clinical spectrum of the 2009 pandemic influenza A (H1N1) infection ranged from self-limited mild illness to progressive pneumonia, or even a fatal outcome. We summarize the clinical manifestations, risk factors for severe and fatal cases, pathologic findings and treatment of this disease in this paper based on current reports from different regions of the world. PMID- 22088543 TI - Fluctuations in the rate of autopsy in China. AB - Autopsy has played a unique role in the progression of clinical medicine, medical education, epidemiology, and public health. However, the autopsy rate has been decreasing during the past several decades worldwide, and its necessity is frequently argued. Autopsy-based research in China, a country with the world's largest population, is very important for studying the spectrum and epidemiology of diseases as well as for discovering new diseases. This article summarizes the brief history of autopsy in China and analyzes the cause of its decline in recent decades by reviewing previously published papers, review articles, self-collected materials, and private correspondence. Since the first officially permitted autopsy in 1913, China witnessed the highest autopsy rate between 1950 and 1970, and since then the autopsy rate began to decline as it in other parts of the world. The main reasons for the reduction in autopsy rates in China include negligence by hospital administrators and relevant government authorities, unmotivated clinicians, helpless pathologists, unenforceable regulations and laws, and local cultures and customs. PMID- 22088544 TI - Genotype and allele frequencies of heme oxygenase-1 promoter region in a Greek cohort. AB - BACKGROUND: Heme oxygenase-1 (HO-1) is an enzyme, which catabolizes heme into carbon monoxide, biliverdin and free iron. The induction of this enzyme is an important cytoprotective mechanism, which occurs as an adaptive and beneficial response to a wide variety of oxidant stimuli. HO-1 inducibility is mainly modulated by a (GT)(n) polymorphism in the promoter region, and has been shown that short (S) repeats are associated with greater up-regulation of HO-1, compared with long (L) repeats. METHODS: In the present study, 250 healthy Greek individuals have been screened in order to estimate the frequencies of (GT)(n) alleles in the HO-1 gene. RESULTS: Nineteen different alleles, ranging from 17 to 39 repeats, with (GT)(23) and (GT)(30) being the most common ones, were identified. CONCLUSION: The possible role of this polymorphism in disease states is discussed. PMID- 22088545 TI - Clinical and imaging features of pulmonary artery sling in infants without significant hemodynamic changes. AB - BACKGROUND: Pulmonary artery sling (PAS) is a rare congenital heart anomaly and may cause unexplained respiratory symptoms in infants. Since the non-specific respiratory symptoms of PAS may lead to misdiagnosis, the aim of this study was to clarify the clinical and imaging features of this disease for timely diagnosis and treatment. METHODS: Clinical histories, physical examinations and imaging studies were retrospectively evaluated in nine infants with PAS. Chest X-ray, echocardiography and contrast-enhanced computed tomography (CT) with 3 dimensional reconstructions were performed in all patients and three of them received surgical treatment. RESULTS: Nine cases included six males and three females with a mean age of (4.3 +/- 2.8) months ranging from 2 to 11 months old. All patients had respiratory symptoms including recurrent cough, stridor and wheezing. The onset of symptoms was within 3 months in all cases and three children had symptoms only a few days after birth. The chest X-ray showed pneumonia in all cases. Contrast-enhanced CT showed the tracheal compression at different lengths in every case. The echocardiograph findings of PAS were anomalous origins of the left pulmonary artery from the posterior aspect of the right pulmonary artery. Of the 9 cases, 8 cases were diagnosed correctly by echocardiography. Of the complicated abnormalities, there were one with secundum atrial septal defect, one with patent foramen ovale and three with persistent left superior vena cava. None of them were complicated with significant blood dynamic changes. CONCLUSIONS: Infants with recurrent respiratory symptoms such as chronic cough, stridor and wheezing, should be examined for the possible presence of congenital pulmonary artery sling. As a noninvasive technique, echocardiography is very helpful and should be the first-choice modality for the diagnosis of pulmonary artery sling. Contrast-enhanced CT, clearly demonstrating the anatomy of pulmonary artery sling and the position and extent of trachea compression, is necessary for the final diagnosis and pre-operation evaluation. PMID- 22088546 TI - Efficacy and safety of intravenous itraconazole followed by oral itraconazole solution in the treatment of invasive pulmonary mycosis. AB - BACKGROUND: Invasive pulmonary mycosis is the most common type of invasive fungal infection. It is often severe and difficult to treat, and is accompanied by high mortality. In this study, we aimed to evaluate the efficacy and safety of intravenous itraconazole followed by oral itraconazole solution in the treatment of invasive pulmonary mycosis and to determine the distribution of different fungi species. METHODS: This was a multi-center, open-label study which enrolled 71 patients who were diagnosed as invasive pulmonary mycosis between July 2007 and January 2009. All patients received intravenous itraconazole therapy followed by oral itraconazole solution with a total treatment duration of 6 weeks. Intravenous itraconazole was given at a dose of 200 mg bid (intravenous infusion every 12 hours) for the first two days, 200 mg qd for the subsequent 12 days. Sequential oral itraconazole solution was given at a dose of 100 mg bid for 4 weeks. Efficacy and safety were assessed according to clinical as well as microbiological criteria. RESULTS: Seventy one patients participated in this study. Of the 60 patients in the full analysis dataset, the clinical response rate was 61.7% and the mycological eradication rate was 66.7%. The overall response rate was 66.7%. Drug-related adverse events occurred in 18.0% of patients: hypokalemia, liver function impairment and mild gastrointestinal side effects were the most common. One patient suffered from severe adverse event, with limb and facial swelling. CONCLUSION: This study showed that in patients with invasive pulmonary mycosis, intravenous itraconazole followed by oral itraconazole solution therapy was safe and effective. PMID- 22088547 TI - Hashimoto encephalopathy: a case report with proton MR spectroscopic findings. AB - A 52-year-old female patient with Hashimoto encephalopathy was admitted to hospital for clinical treatment, and the findings on MR spectroscopy (MRS) and MR imaging (MRI) in the brain were reported. MRS revealed the decreases in N acetylaspartate (NAA/Cr=1.19) and myo-inositol peaks, and the elevations in lipid, lactate, glutamate/glutamine multiplet and choline (Cho/Cr=1.21) peaks which supported a cerebral inflammatory change, in addition to multifocal hyperintensities on T2WI and fluid-attenuated inversion recovery (FLAIR) images, slight hyperintensities on diffusion weighted imaging (DWI), hypointensities on T1WI. The atrophy of the brain was revealed on follow-up MRI two years later. PMID- 22088548 TI - Littoral cell angioma of the spleen: report of three cases and a review of the literature. AB - Littoral cell angioma is a recently described rare vascular tumor of the spleen. The clinical course of this benign tumor is asymptomatic in most patients. Herein, we described three patients with littoral cell angioma detected during physical examination. A brief discussion and review of a handful of cases of splenic littoral cell angioma, which have been previously reported in the English language literature, are performed in this paper. PMID- 22088549 TI - Very late coronary aneurysm formation with subsequent stent thrombosis secondary to drug-eluting stent. AB - Drug-eluting stents have changed the practice in interventional cardiology. With the widespread use of these stents important safety concerns regarding stent thrombosis and formation of coronary artery aneurysm have been expressed. While the majority of attention was focused on stent thrombosis, the formation of coronary aneurysm was only described in anecdotal reports. We report on a patient who suffered from very late stent thrombosis in association with coronary artery aneurysm formation secondary to drug-eluting stent but not to bare-metal stent. PMID- 22088550 TI - Coexisting ankylosing spondylitis and rheumatoid arthritis: a case report with literature review. AB - A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen (HLA) B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control. PMID- 22088551 TI - A rare case of circumferential intramural dissection of thoracic esophagus with contained esophageal perforation. AB - In this report, a full account of an extremely rare case on esophageal intramural dissection (EID) is presented. A 56-year-old female patient, misdiagnosed as esophageal mediastinal fistula under endoscopic view, was diagnosed correctly as EID with contained esophageal perforation in the operation and cured by thoracic esophagectomy. PMID- 22088552 TI - Laparoscopic treatment of a massive fibroepithelial polyp accompanied by ureteral intussusception. AB - Ureteral fibroepithelial polyp accompanied by intussusception is a rare occurrence. Currently, most ureteral polyps could be removed readily by ureteroscopy. Nevertheless, endoscopic resection can be difficult in patient with a large polyp, especially accompanied by an intussusception. We described our experience and laparoscopic technique for treatment of a symptomatic 63-year-old woman who presented with a pedunculated, 9-cm-long, left lower ureteral, fibroepithelial polyp accompanied by a 2-cm-long intussusception. PMID- 22088553 TI - Meningitis caused by Enterococcus casseliflavus with refractory cerebrospinal fluid leakage following endoscopic endonasal removal of skull base chondrosarcoma. PMID- 22088554 TI - [Myoma and pregnancy: when medical treatment is not sufficient]. AB - The leiomyoma is the most common benign uterine tumor in population of childbearing age women. We report a patient case with uterine myomas threatening the pregnancy continuation and causing a real problem of maternal tolerance. In presence of a 22 cm subserosal fibroma which is responsible of a severe abdominal pain syndrome resistant to level 3 analgesics, the use of surgical treatment was considered, even if current recommendations are for an optimal medical management. Myomectomy by laparotomy has been performed after 13 weeks of gestation. PMID- 22088555 TI - A survey of ward nurses attitudes to the Intensive Care Nurse Consultant service in a teaching hospital. AB - The aim of an Intensive Care Nurse Consultant (ICNC) service is to optimise care of complex ward patients and reduce adverse events. Despite their widespread implementation, specific assessment of ward nurses' attitudes towards such is lacking. Accordingly, we surveyed ward nurses' attitudes towards our ICNC service in five domains: (a) accessibility and approachability; (b) perceived ICNC skill and knowledge; (c) perceived influence on patient management; (d) usefulness as a resource of clinical information; (e) impact upon adverse outcomes. To achieve this, an anonymous Liker-type questionnaire was distributed to 208 ward nurses in our hospital. We also included space for free text. Completed questionnaires were entered manually into a SURVEYMONKEYTM pro-forma to permit automatic report generation and results summary. The major findings were that ICNC staff were perceived as being approachable and good communicators, were skilled at early detection of deteriorating patients, and that they reduce serious adverse events. In addition, nurses believe the ICNC service provides continuity of care post discharge from the intensive care unit (ICU), as well as assisting staff to prioritise clinical issues following medical emergency team (MET) review or ICU discharge. The ward nurses did not believe that the ICNC service reduced their skills in managing ward patients. In contrast, respondents stated that the ICNC service needed to improve the processes of referral to allied health and education of ward staff regarding deteriorating patients. Finally, ward nurses suggest they would call the MET service rather than the ICNC service for patients who had already deteriorated. This survey suggests that the ICNC service is valued, and is perceived to prevent the development of adverse events, rather than playing a major role in the management of the deteriorating patient. There is a need to improve referrals to allied health and further educate ward nurses. PMID- 22088556 TI - Assessment of the effects of AZD3480 on cognitive function in patients with schizophrenia. AB - AZD3480 is a selective agonist of alpha4beta2 central neuronal nicotinic receptors (NNRs). This study investigated its effects on cognition, relative to placebo, in 440 patients with stable schizophrenia who were taking a single atypical antipsychotic medication and who were active cigarette smokers. Mean age was 41 (range 19 to 55) years and the majority of patients (88%) had a diagnosis of paranoid schizophrenia. Patients were randomized to one of 3 doses of AZD3480: 5 mg, 20 mg, and 35/100 mg (depending on CYP2D6 metabolic status), or to placebo. Treatment was given once daily for 12 weeks. The primary outcome measure was change in cognitive function from baseline to Week 12, as measured by IntegNeuro computerized test battery of cognitive function scores. Secondary outcome measures included assessment of functional capacity (University of California at San Diego Performance Based Skills Assessment [UPSA2]) and adaptive function (Social Functioning Scale [SFS]). AZD3480 failed to improve cognition relative to placebo in this population of patients or in subpopulations defined by disposition, metabolic status, antipsychotic treatment, age, age of illness onset, and sex. Likewise, no improvement relative to placebo was observed in either the SFS measure of adaptive functioning or the UPSA2 measure of functional capacity. AZD3480 was generally well tolerated in the population studied. PMID- 22088557 TI - Orthorexia nervosa presenting as prodrome of schizophrenia. PMID- 22088558 TI - Structural studies of lead lithium borate glasses doped with silver oxide. AB - Silver oxide doped lead lithium borate (LLB) glasses have been prepared and characterized. Structural and composition characterization were accessed by XRD, FTIR, Raman, SEM and EDS. Results from FTIR and Raman spectra indicate that Ag(2)O acts as a network modifier even at small quantities by converting three coordinated to four coordinated boron atoms. Other physical properties, such as density, molar volume and optical basicity are also evaluated. Furthermore, they are also affected by the silver oxide composition. PMID- 22088559 TI - Estimation of the rotamerization constants of different conformations of N acetylalanine: a theoretical and matrix-isolation FT-IR study. AB - The conformational landscape of N-acetylalanine has been investigated by a theoretical and matrix-isolation FT-IR study. Optimizations of N-acetylalanine structures has been conducted at successive higher levels of theory HF/3-21G, DFT(B3LYP)/6-31++G** and MP2/6-31++G**. This resulted in three stable conformations. Among these, one conformation contains an intramolecular H-bond. The vibrational properties of these conformations were calculated and used to identify the conformations in a cryogenic argon matrix. The intensities of some bands assigned to a particular conformation were used to estimate the rotamerization constants K(r12) and K(r13) for the equilibria NAA1 NAA2 and NAA1 NAA3, respectively. The obtained experimental values were in agreement with the theoretical predictions. PMID- 22088560 TI - Unidirectional growth of benzil crystal from solution by Sankaranarayanan Ramasamy method and its characterization. AB - Good quality <100> benzil single crystal with a diameter 18 mm and length 75 mm was successfully grown from solution by the unidirectional growth method of Sankaranarayanan-Ramasamy (SR) for the first time in the literature. The seed crystals have been harvested from conventional solution growth technique and subsequently used for unidirectional growth. The grown crystal was subjected to various characterization studies. The results of UV-vis spectral analysis, photoluminescence, etching and microhardness studies were compared with conventional solution grown crystal to that of SR method grown crystal. The quality of SR method grown benzil crystal is better than conventional solution grown crystal. PMID- 22088561 TI - Kidney-derived proteins in urine as biomarkers of induced acute kidney injury in sheep. AB - Acute kidney injury (AKI) is a life-threatening condition for which an early diagnosis is problematic. The aim of the present study was to identify kidney derived urinary proteins specific to AKI in sheep. AKI was induced in six sheep by an overdose of ketoprofen. Six untreated sheep served as controls. Urine samples were collected for up to 24 h after drug administration and pooled according to time and treatment. Tissue samples from kidney were taken immediately after euthanasia. Urinary proteins were separated by two-dimensional gel electrophoresis (2DE) and the proteins of interest were identified by mass spectrometry. Calbindin-D28k, retinol-binding protein 4 and CD1d were identified in ketoprofen-treated sheep, but not in controls. In addition, calbindin-D28k and CD1d were localized in kidney tissues by immunohistochemical staining. These preliminary results suggest that urinary calbindin-D28k and CD1d represent potential useful biomarkers of AKI, at least in sheep. PMID- 22088563 TI - Post hoc ergo propter hoc: complications and death after gastrostomy placement. PMID- 22088562 TI - Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell mediated autoimmunity. AB - Pro-inflammatory T cells mediate autoimmune demyelination in multiple sclerosis. However, the factors driving their development and multiple sclerosis susceptibility are incompletely understood. We investigated how micro-RNAs, newly described as post-transcriptional regulators of gene expression, contribute to pathogenic T-cell differentiation in multiple sclerosis. miR-128 and miR-27b were increased in naive and miR-340 in memory CD4(+) T cells from patients with multiple sclerosis, inhibiting Th2 cell development and favouring pro inflammatory Th1 responses. These effects were mediated by direct suppression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and interleukin-4 (IL4) expression, resulting in decreased GATA3 levels, and a Th2 to Th1 cytokine shift. Gain-of-function experiments with these micro-RNAs enhanced the encephalitogenic potential of myelin-specific T cells in experimental autoimmune encephalomyelitis. In addition, treatment of multiple sclerosis patient T cells with oligonucleotide micro-RNA inhibitors led to the restoration of Th2 responses. These data illustrate the biological significance and therapeutic potential of these micro-RNAs in regulating T-cell phenotypes in multiple sclerosis. PMID- 22088564 TI - Expression of dentine sialophosphoprotein in mouse nasal cartilage. AB - OBJECTIVE: Dentine sialophosphoprotein (DSPP) was initially thought to be unique for dentine formation during tooth development, whilst recent reports have shown a much broader expression pattern such as in bone, periodontium and inner ear. Our goal was to explore its expression and potential impact during early nasal cartilage formation in comparison with tooth development. STUDY DESIGN: We investigated DSPP expression in the nasal cartilage by immunohistochemistry and in situ hybridisation. We also cloned a 719bp partial DSPP cDNA from nasal cartilage and analysed its homology to the published mouse DSPP cDNA sequence. In addition, quantitative RT-PCR was undertaken to compare the expression pattern of DSPP in nasal cartilage and tooth germs during embryonic development. RESULTS: The expression of DSPP in mouse nasal chondrocytes was detected using in situ hybridisation and immunohistochemical staining. The quantitative RT-PCR data showed that expression levels of DSPP in nasal cartilage are similar to that of tooth: low at E18, and increased during development with the peak level at P3. Furthermore, DSPP levels in nasal cartilage are lower than tooth but higher than bone. CONCLUSION: DSPP is expressed in nasal cartilage, and a similar temporal expression pattern in cartilage and tooth indicates the potential importance of DSPP during development. PMID- 22088565 TI - Wilms' tumor metastatic to bilateral testes at presentation: case and review of the literature. AB - A 7-year-old male with bilateral palpable testicular masses was found to have metastatic stage IV Wilms' tumors associated with both left renal and lung lesions. The patient was treated successfully with testicular-sparing bilateral partial orchiectomies, radical nephrectomy, chemotherapy, and radiation, with 8 years free of recurrence. This is the only reported case of bilateral testicular tumors from metastatic Wilms' tumor that were present at the initial presentation. A review of the literature of all previous reported cases of metachronous or related testicular metastatic Wilms' tumors is reported. PMID- 22088566 TI - Is routine postoperative chest radiography needed after percutaneous nephrolithotomy? AB - OBJECTIVE: To assess whether routine postoperative chest radiography (CXR) is required after percutaneous nephrolithotomy (PCNL) for the detection and possible management of hydropneumothorax. It is the standard for many urologists to obtain routine postoperative CXRs after PCNL to assess for hydropneumothorax. However, it has been our experience that in the few patients who develop hydropneumothorax, the CXR findings almost never affect the clinical management. METHODS: A retrospective review was performed of 214 PCNL procedures acquired from 2007 to 2010. The data analyzed included patient demographics, operative data, postoperative CXR findings, and complications. RESULTS: We reviewed 214 PCNL procedures, 49% of the 164 patients were men, with a mean age of 48 years and a mean stone burden of 2.4 * 2.5 cm. Renal access was obtained by the urologists in 47% of cases. Renal access was obtained in the upper pole (51%), midpole (26%), and lower pole (23%) through the 11th-12th intercostal space (21%) and below the 12th rib (78%). Renal access was unsuccessful in 2.8%. All patients underwent postoperative CXR. Only 2 patients (1%) had a hydropneumothorax, and both had clinical symptoms. One patient's postoperative CXR findings were minimal pleural effusion only. Both patients were treated with tube thoracostomy. The mean hospital length of stay was 1.6 days, and the mortality rate was 0.5%. CONCLUSION: Routine postoperative CXR is not needed after PCNL. Obtaining selective CXR when a recognized intraoperative hydropneumothorax has occurred, the physical examination reveals an abnormality, or the patient experiences respiratory difficulties in the postoperative period is safe, cost-effective, and reduces unnecessary radiation exposure to the patients. PMID- 22088567 TI - Long-term biochemical recurrence rates after robot-assisted radical prostatectomy: analysis of a single-center series of patients with a minimum follow-up of 5 years. AB - OBJECTIVE: To address the long-term biochemical recurrence (BCR)-free survival rates of patients treated with robotic-assisted laparoscopic prostatectomy (RALP) with a minimum follow-up of 5 years. MATERIALS AND METHODS: Prospectively collected data of 184 patients treated with RALP at a single institution were analyzed. Kaplan-Meier and life tables analyses targeted the rates of BCR according to pathologic parameters. Cox regression analyses addressed predictors of BCR. RESULTS: Median follow-up was 67.5 months. One and 10 patients died of prostate cancer (PCa) and other causes, respectively. Mean time to BCR was 83.8 months. The 3-, 5-, and 7-year BCR-free survival rates were 94%, 86%, and 81%, respectively. These rates were 97%, 93%, and 85% for pT2 disease; 94%, 84%, and 84% for pT3a; and 69%, 43%, and 43% for pT3b (P<.001). The same figures were 97%, 90%, and 88% for Gleason sum 6 or lower; 90%, 86%, and 75% for Gleason sum 7; and 85%, 65%, and 65% for Gleason sum 8-10 (P=.01). At univariable analyses, prostate specific antigen, pathologic Gleason score, and presence of extracapsular extension, seminal vesicle invasion, and adjuvant radiotherapy were significantly associated with BCR. At multivariable analysis, the presence of seminal vesicle invasion and the presence of Gleason sum 8-10 represented independent predictors of BCR (HR=5.14; P=.004 and HR=3.04; P=.04, respectively). CONCLUSION: We report the longest available follow-up in RALP patients. RALP represents an oncologically effective procedure. Our oncological results support the increasing diffusion of RALP for the treatment of organ-confined PCa. PMID- 22088568 TI - Oligohydramnios associated with sonographically normal kidneys. AB - We report a male newborn presenting with sonographically normal kidneys, oligohydramnios during late pregnancy, and persisting anuric renal failure. Despite intensive treatment, the patient suffered from severe hypotension and died at the age of 4 weeks. At autopsy, kidneys were found to be normal; on histology, deranged renal structures, in particular proximal tubuli and vessels, were noted, leading to the diagnosis of renal tubular dysgenesis (RTD). The diagnosis was confirmed by 2 heterozygous nonsense mutations of the ACE gene. Because the recurrence rate of RTD is 25% for the autosomal recessive trait, knowledge and genetic diagnosis of the disease is important for the parents. PMID- 22088569 TI - Shock wave lithotripsy and diabetes mellitus: a population-based cohort study. AB - OBJECTIVE: To determine if shock wave lithotripsy (SWL) is associated with diabetes mellitus (DM) in a community setting. The pancreas is vulnerable to injury at SWL as evidenced by case studies; thus, concern exists for the development of DM after SWL. METHODS: The Rochester Epidemiologic Project was used to identify all Olmsted County, Minnesota residents diagnosed with urolithiasis from 1985 to 2008. New-onset DM was identified by diagnostic codes and treatment with SWL by surgical codes. Cox proportional hazards models were used to determine the risk of DM after SWL therapy. RESULTS: A total of 5287 incident cases of stone formation without pre-existing DM and with >=3 months of follow-up. After an average follow-up of 8.7 years, 423 patients (8%) were treated with SWL and new-onset DM had developed in 743 (12%). The diagnosis of DM followed SWL in 77 patients. However, no association was evident between SWL and the development of DM before (hazard ratio 0.98, 95% confidence interval 0.76 1.26) or after (hazard ratio 0.92, 95% confidence interval 0.71-1.18) SWL, controlling for age, sex, and obesity. CONCLUSION: In the present large, population-based cohort, the long-term risk of developing DM was not increased in persons who underwent SWL to treat their kidney stones. PMID- 22088570 TI - Isolated large hydatid cyst in the kidney of an elderly man. AB - Cystic disease (CD) is a parasitic infestation by Echinococcus granulosus and occurs endemically in many countries, associated with sheep farming. Renal involvement is rare (2-4%) and is often indicative of disseminated disease. Echinococcal larvae can reach the kidneys through the bloodstream or lymph glands or through a direct route. The larvae grow slowly, and patients bearing larvae are typically asymptomatic. We report the case of a 79-year-old male with an isolated hydatid cyst in the kidney and describe its management by transperitoneal nephrectomy. Diagnosis was based on epidemiology and imaging findings, and was confirmed by histopathological and serum examinations. PMID- 22088571 TI - On-demand tramadol hydrochloride use in premature ejaculation treatment. AB - OBJECTIVES: To determine the efficacy of tramadol in premature ejaculation (PE) treatment compared with placebo. METHODS: A single-blind, placebo-controlled, crossover study was conducted with 60 lifelong (primary) patients with PE. The patients were randomized into 2 groups, each consisting of 30 patients, who took tramadol or placebo on demand. PE was defined as an intravaginal ejaculation latency time of <=60 seconds in 90% of intercourse episodes. The efficacy of the drugs was assessed using the intravaginal ejaculation latency time, ability of ejaculation control, and sexual satisfaction scores after an 8-week treatment period. RESULTS: All participants completed the study voluntarily. Two groups were similar in terms of the patient demographics. Increases in the intravaginal ejaculation latency time, ability of ejaculation control, and sexual satisfaction score between the placebo and tramadol groups were compared with the baseline values in both groups. At the end of study period, the tramadol group had significantly (P<.001) greater values for all 3 parameters compared with those in the placebo group. CONCLUSIONS: On-demand use of low-dose tramadol is effective for lifelong PE. Currently, selective seratonin reuptake inhibitors such as dapoxetine, are a more popular treatment option for PE. However, tramadol might be considered an alternative agent for primary PE treatment. PMID- 22088572 TI - Metastatic prostate carcinoma mimicking primary anal cancer. AB - A 71-year-old man with a history of castration-refractory prostate cancer was initially treated with hormonal therapy. He responded with a decreasing prostate specific antigen level and improved symptoms. Chemotherapy was initiated later, after an increasing prostate-specific antigen level and findings of distant metastases. Nine months after his initial diagnosis, he presented with a large multinodular perianal mass that was suspicious for primary anal cancer. Biopsy revealed poorly differentiated metastatic prostate carcinoma. The patient died 2 months after the initial presentation with perianal skin metastasis. PMID- 22088573 TI - Juvenile granulosa cell tumor arising from intra-abdominal testis in newborn: case report and review of the literature. AB - In the present case, the neonate presented with a left-sided abdominal mass and an empty left scrotum. Abdominal ultrasonography showed well-defined cystic formation, and laparotomy revealed a tumor arising from an intra-abdominal left testis. The carcinoembryonic antigen and neuron-specific enolase levels were within normal limits, and the serum beta-human chorionic gonadotropin and alpha fetoprotein levels were within age-related normal values. The findings from the immunochemistry tests confirmed the diagnosis. PMID- 22088574 TI - [Solitary intrasellar plasmocytoma revealed by a diplopia: a case report]. AB - INTRODUCTION: Plasmocytomas rarely invade the skull base. It can be solitary or multiple. The clinical presentation mainly consists in a progressive neuropathy involving many cranial nerves, or may simply present as an optochiasmatic syndrome. OBSERVATION: The authors report a case of a female patient aged 68 years presenting with an optochiasmatic syndrome with an anosmia and paralysis of the right sixth (VI) cranial nerve progressing over two years prior to her hospitalisation. Cerebral MRI showed a voluminous intrasellar lesion, isointense on T1 and hyperintense on T2, enhancing intensely after gadolinium injection with evidence of invasion of the sphenoid and cavernous sinuses. The endocrinologic assay was normal. A sphenoidal biopsy by the rhinoseptal route permitted the diagnosis of a plasmocytoma. A complete radiologic and laboratory assessment of the patient was accomplished, the patient benefited from local radiotherapy. DISCUSSION: Plasmocytomas are malignant tumors that are essentially osseous. The cervicocephalic region is rarely afflicted (1%). Extension to the cranial base seldom occurs. Less than 30 cases have been described in the literature simulating the other numerous neoplastic intrasellar lesions. CONCLUSION: Plasmocytomas of the cranial base revealing a myeloma represent a very rare entity. Nevertheless, whether solitary or multiple, a plasmocytoma must be considered amongst the differential diagnoses in the face of any invasive lesion of the sphenoid sinus. PMID- 22088576 TI - A randomized trial comparing gentamicin/citrate and heparin locks for central venous catheters in maintenance hemodialysis patients. AB - BACKGROUND: Central venous catheters (CVCs) are used for vascular access in hemodialysis patients who have no alternative access or are awaiting placement or maturation of a permanent access. The major complications of CVCs are catheter related bloodstream infection and clotting in the catheter lumen. STUDY DESIGN: Parallel-group, randomized, multicenter clinical trial, with patients blinded to study intervention. SETTING & PARTICIPANTS: 16 free-standing dialysis facilities in Northern California belonging to a single provider. 303 adult maintenance hemodialysis patients who were using a tunneled cuffed CVC for vascular access. INTERVENTION: The treatment group received an antibiotic lock containing gentamicin 320 MUg/mL in 4% sodium citrate, whereas the control group received the standard catheter lock containing heparin 1,000 U/mL. Both groups received triple-antibiotic ointment on the catheter exit site during dressing changes at each dialysis treatment. OUTCOMES: Catheter-related bloodstream infection and catheter clotting. MEASUREMENTS: Catheter-related bloodstream infection was defined as the occurrence of symptoms consistent with bacteremia together with positive blood culture results in the absence of another obvious source of infection. Catheter clotting was measured as the rate of thrombolytic agent use required to maintain adequate blood flow. A single patient could contribute more than one infection or clotting episode. RESULTS: The rate of catheter-related bloodstream infection was 0.91 episodes/1,000 catheter-days in the control group and 0.28 episodes/1,000 catheter-days in the treatment group (P = 0.003). The time to the first episode of bacteremia was significantly delayed (P = 0.005). The rates of tissue plasminogen activator use were similar in the treatment and control groups: 2.36 versus 3.42 events/1,000 catheter-days, respectively (P = 0.2). LIMITATIONS: The requirement for dialysis facility staff to prepare the treatment intervention prevented a completely blinded study. CONCLUSION: Gentamicin 320 MUg/mL in 4% sodium citrate used as a routine catheter lock in CVCs in patients on maintenance hemodialysis therapy markedly decreases the incidence of catheter-related bloodstream infection and is as effective as heparin 1,000 U/mL in preventing catheter clotting. PMID- 22088575 TI - A complex multilevel attack on Pseudomonas aeruginosa algT/U expression and algT/U activity results in the loss of alginate production. AB - Infection by the opportunistic pathogen Pseudomonas aeruginosa is a leading cause of morbidity and mortality seen in cystic fibrosis (CF) patients. This is mainly due to the genotypic and phenotypic changes of the bacteria that cause conversion from a typical nonmucoid to a mucoid form in the CF lung. Mucoid conversion is indicative of overproduction of a capsule-like polysaccharide called alginate. The alginate-overproducing (Alg(+)) mucoid phenotype seen in the CF isolates is extremely unstable. Low oxygen tension growth of mucoid variants readily selects for nonmucoid variants. The switching off mechanism has been mapped to the algT/U locus, and the molecular basis for this conversion was partially attributed to mutations in the algT/U gene itself. To further characterize molecular changes resulting in the unstable phenotype, an isogenic PAO1 derivative that is constitutively Alg(+) due to the replacement of the mucA with mucA22 (PDO300) was used. The mucA22 allele is common in mucoid CF isolates. Thirty-four spontaneous nonmucoid variants, or sap (suppressor of alginate production) mutants, of PDO300 were isolated under low oxygen tension. About 40% of the sap mutants were rescued by a plasmid carrying algT/U (Group A). The remaining sap mutants were not (Group B). The members of Group B fall into two subsets: one similar to PAO1, and another comparable to PDO300. Sequence analysis of the algT/U and mucA genes in Group A shows that mucA22 is intact, whereas algT/U contains mutations. Genetic complementation and sequencing of one Group B sap mutant, sap22, revealed that the nonmucoid phenotype was due to the presence of a mutation in PA3257. PA3257 encodes a putative periplasmic protease. Mutation of PA3257 resulted in decreased algT/U expression. Thus, inhibition of algT/U is a primary mechanism for alginate synthesis suppression. PMID- 22088578 TI - Initial fixation strength of transosseous-equivalent suture bridge rotator cuff repair is comparable with transosseous repair. AB - BACKGROUND: The outcome of rotator cuff repair correlates with tendon healing. Early studies of arthroscopic rotator cuff repair demonstrate lower healing rates than traditional open techniques. Transosseous-equivalent repair techniques (suture bridge) were developed to improve the initial fixation strength. PURPOSE: To compare the initial in vitro tensile fixation strength of a transosseous equivalent suture bridge (TOE-SB) rotator cuff repair construct to a traditional transosseous (TO) suture construct. STUDY DESIGN: Controlled laboratory study. METHODS: Identical simulated rotator cuff tears were created on 8 matched pairs of humeri. Each matched pair underwent repair with 4 sutures using either the TOE SB or TO technique. Initial fixation strength was tested in a custom testing jig. Each shoulder underwent 1000 cycles each of low and then high load testing. Gap displacement was measured at anterior and posterior sites of the repair with digital video tracking of paired reflective markers and recorded at predetermined cycle intervals. RESULTS: There were no statistically significant differences in gap formation at the repair sites under low or high load conditions between TOE SB and TO techniques. The mean maximal gap formation of the repairs during low load testing in the TOE-SB and TO constructs was 0.93 +/- 0.88 mm and 0.55 +/- 0.22 mm, respectively (P = .505). The mean maximal gap formation during high load testing in the TOE-SB and TO constructs was 2.04 +/- 1.10 mm and 2.28 +/- 1.62 mm, respectively (P = .517). The most significant increase in gap distance occurred at the transition from low load to high load in both constructs. Most of the incremental displacement occurred within the first 100 cycles for both high and low load testing (P < .001). CONCLUSION: The arthroscopic TOE-SB technique is comparable in initial fixation strength to the traditional TO simple suture repair technique. CLINICAL RELEVANCE: Arthroscopic techniques can achieve initial fixation strength comparable with traditional TO techniques performed without suture anchors. PMID- 22088579 TI - Biomechanical and histological evaluations of the doubled semitendinosus tendon autograft after anterior cruciate ligament reconstruction in sheep. AB - BACKGROUND: A sheep or goat anterior cruciate ligament (ACL) reconstruction model with the semitendinosus tendon autograft has not as of yet been established. HYPOTHESIS: The semitendinosus tendon graft may be necrotized after ACL reconstruction until 12 weeks. Structural properties of the femur-graft-tibia complex may not be restored to the normal ACL level even at 12 months after surgery. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty-eight mature sheep were used. In each animal, the right knee underwent ACL reconstruction using the semitendinosus tendon autograft. Two of them were not tested because of pneumonia. Twenty of 36 sheep were used for biomechanical evaluations. Five randomly selected animals were sacrificed at 0, 12, 24, or 52 weeks after surgery. In each animal, both the knees were harvested, and the left knee was used to obtain the control data. The remaining 16 sheep were used for histological evaluation. Two or 3 randomly selected animals were sacrificed at 0, 2, 6, 12, 24, or 52 weeks after surgery. RESULTS: The tendon graft was predominantly acellular at 2 weeks. Although cell infiltration increased at 6 weeks, the core portion remained necrotic even at 12 weeks. At 24 and 52 weeks, the necrotic lesion disappeared in the core portion. In each period, the anteroposterior translation of the reconstructed knee remained significantly greater than that of the control (P < .0001). At 52 weeks, the maximum load of the femur-graft-tibia complex was significantly lower than that of the femur-ACL tibia complex (P < .0001), although there was no significant difference in the cell density, the tissue dimensions, the stiffness, and the elongation at failure between the 2 complexes. CONCLUSION: The sheep ACL reconstruction model showed predominant intrinsic fibroblast necrosis in the tendon autograft until 12 weeks. Although the structural properties of the femur-graft-tibia complex gradually improved, they were not completely restored to the femur-ACL-tibia complex level even at 52 weeks. CLINICAL RELEVANCE: Remodeling of the semitendinosus tendon autograft after ACL reconstruction is not different from that of the bone-tendon bone graft. This study has suggested that vigorous activity should not be permitted for patients in the early periods after ACL reconstruction using semitendinosus tendon autografts, which are necrotized and weakened after surgery. PMID- 22088577 TI - Depressed mood enhances anxiety to unpredictable threat. AB - BACKGROUND: Depression and anxiety disorders (ADs) are highly co-morbid, but the reason for this co-morbidity is unclear. One possibility is that they predispose one another. An informative way to examine interactions between disorders without the confounds present in patient populations is to manipulate the psychological processes thought to underlie the pathological states in healthy individuals. In this study we therefore asked whether a model of the sad mood in depression can enhance psychophysiological responses (startle) to a model of the anxiety in ADs. We predicted that sad mood would increase anxious anxiety-potentiated startle responses. METHOD: In a between-subjects design, participants (n=36) completed either a sad mood induction procedure (MIP; n=18) or a neutral MIP (n=18). Startle responses were assessed during short-duration predictable electric shock conditions (fear-potentiated startle) or long-duration unpredictable threat of shock conditions (anxiety-potentiated startle). RESULTS: Induced sadness enhanced anxiety- but not fear-potentiated startle. CONCLUSIONS: This study provides support for the hypothesis that sadness can increase anxious responding measured by the affective startle response. This, taken together with prior evidence that ADs can contribute to depression, provides initial experimental support for the proposition that ADs and depression are frequently co-morbid because they may be mutually reinforcing. PMID- 22088580 TI - Should complementary and alternative medicine familiarisation modules be taught in African medical schools? AB - Complementary and alternative medicines (CAMs) are household sources of therapy in African communities. A large percentage of the African population uses CAMs as an alternative to mainstream medicine. This is partly due to tradition, and partly because of inability to afford conventional treatments. In the developed countries, the use of CAMs is gradually on the increase. As a result, certain medical schools in these countries are incorporating CAM familiarisation modules into their undergraduate medical curricula. In Africa, most medical schools have not taught CAM yet. However, in view of the rising use of CAMs by the African populace, and the potential CAM-conventional therapy interactions, there is the need for physicians to get familiar with those CAMs in common use. To achieve this, it is recommended that African medical schools introduce CAM familiarization modules into the undergraduate medical curricula. This would fully prepare the 21st century doctors to deliver holistic medical treatment, and thus be at par with the global trend. PMID- 22088581 TI - An updated review on medicinal herb genus Spilanthes. AB - Herbal medicine has been used in medical practice for thousands of years and recognized especially as a valuable and readily available resource for healthcare in Asian nations. India is a vast repository of medicinal plants that can be developed as a safe and economical system of medicine for the treatment of various ailments. Unfortunately, most of the traditionally used medicinal plants are yet unexplored or have not been fully examined by modern medical science. Therefore, exploring traditionally reported medicinal plants to leverage their potential for the betterment of human health is of great importance. The present review examines a promising medicinal plant genus Spilanthes. In recent years, many new compounds and activities of this plant genus have been established. The present review therefore, aims to compile up-to-date and comprehensive information of genus Spilanthes with special emphasis on phytochemical and ethnomedical uses, scientifically documented pharmacological activities and tissue culture methods for conservation. PMID- 22088582 TI - [Icariin and its pharmaceutical efficacy: research progress of molecular mechanism]. AB - Icariin is one of the key active components of Epimedium species, which is most widely applied to supplement the kidney in traditional Chinese medicine. Scientific research has found that icariin possesses extensive therapeutic effects such as protecting neurons from injury, promoting growth of neuronal synapse, improving sexual dysfunction and bone morphogenesis, as well as anti inflammation, anti-tumor and anti-depression functions. Considering that molecular mechanism is the fundamental basis for pharmaceutical efficacy of icariin, in this article, the authors retrospectively retrieved 122 scientific papers recorded in the PubMed database with "icariin" in the title from January 1, 1995 to January 5, 2011. It was found that icariin has been closely highlighted in the intervention of p38 mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt signal pathways, inhibition of phosphodiesterase 5, and regulation of nuclear receptors. Besides, the authors also discussed the main orientation for molecular mechanism of icariin in future research. PMID- 22088583 TI - Estimation of sample size and testing power (part 2). AB - This article introduces definitions of three special tests, namely, non inferiority test (to verify that the efficacy of the experimental drug is clinically not inferior to that of the positive control drug), equivalence test (to verify that the efficacy of the experimental drug is equivalent to that of the control drug) and superiority test (to verify that the efficacy of the experimental drug is superior to that of the control drug), and methods of sample size estimation under the three different conditions. By specific examples, the article introduces formulas of sample size estimation for the three special tests, and their SAS realization in detail. PMID- 22088584 TI - Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study. AB - BACKGROUND: Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby may produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is hydroxycitric acid (HCA) derived from Garcinia cambogia Desr. METHODS AND DESIGN: The objective of this article is to describe the protocol of a clinical trial designed to directly test the effects of Garcinia cambogia derived HCA on food intake, satiety, weight loss and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight or obese individuals (with a body mass index range of 25.0 to 39.9 kg/m(2)) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia derived HCA on food intake, satiety, weight loss, and oxidative stress levels. Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day. This study can be completed with far fewer subjects than a parallel design. DISCUSSION: Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA is selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01238887). PMID- 22088585 TI - [Study protocol for a self-controlled case study to evaluate the safety and standardization for external application of Chinese medicine Jiuyi Powder]. AB - BACKGROUND: As the main medicinal powder for drawing out pus and removing necrotic tissue in external therapies of traditional Chinese surgery, Sheng Powder has made great contributions to the treatment of inflammatory wounds and has the unique bactericidal and decay-discharging function that can not be replaced by antibiotics. However, Sheng Powder has toxicity because it contains mercury. So far, there is no clinical research on the standards of dose and usage of Sheng Powder and there is a lack of objective and quantitative criteria for operating standards and monitoring of toxicity and side effects. Therefore, the authors choose Jiuyi Powder, one of the most commonly used Sheng Powder, to evaluate the safety of its external use, and form a standardization program for clinical implementation. METHODS AND DESIGN: This study is a nonrandomized, nonblinded, self-controlled case study. There will be two key stages in the study. In stage one, 10 patients with plasma cell mastitis will be enrolled. The patients will receive continuous external application of Jiuyi Powder with a fixed dose (160 mg/d). Blood mercury and urine mercury levels will be dynamically tested at different time intervals, and the observation of pharmacokinetic parameters will be conducted after Jiuyi Powder has been absorbed by the surface of the wound. In stage two, 30 patients with each of the four conditions including postoperative wounds of head or facial surgeries, plasma cell mastitis, anal fistula and chronic absorption ulcer of the shank will be enrolled, respectively. According to the dose of 1.5 mg/cm(2), Jiuyi Powder will be externally applied to the wound surface for 14 d. On the basis of the first-phase study, the test time will be chosen and the toxicity outcome will be detected to evaluate the safety of external application of Jiuyi Powder and to establish recommendations for standardized clinical use. DISCUSSION: The purpose of this study is to evaluate the safety of the external application of Jiuyi Powder through a two-stage study. The pharmacokinetic parameters of external application of Jiuyi Powder at the clinical dose range, the changes in blood and urinary mercury levels and related safety indexes will be observed on different wounds located in different positions externally. The evaluation of whether Jiuyi Powder could be a routine medication for drawing out pus and removing necrotic tissue in inflammatory and refractory wounds will be stated. TRIAL REGISTRATION NUMBER: ChiCTR-TNC-11001366. PMID- 22088586 TI - [Acupuncture combined with Chinese herbal medicine Plantain and Senna Granule in treatment of functional constipation: a randomized, controlled trial]. AB - BACKGROUND: Functional constipation is one of the most common gastrointestinal diseases. Currently, there is no effective Western medical therapy for functional constipation and it significantly impacts the quality of life of the patients. Integrated traditional Chinese and Western medicine therapies were reported to have better therapeutic effects than routine Western medicine therapies. OBJECTIVE: To explore the efficacy of acupuncture combined with Chinese herbal medicine Plantain and Senna Granule in the treatment of functional constipation. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 390 patients with confirmed functional constipation enrolled from the Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical College in China from February 2008 to January 2010 were randomly divided into three groups, with 130 cases in each group. Acupuncture group was treated with puncture of point Tianshu (ST25), Shangjuxu (ST37), Zusanli (ST36), Dachangyu (BL25) and Zhigou (SJ6) twice daily for four weeks, while Plantain and Senna Granule group was treated with 5 g of Plantain and Senna Granule once daily, and the combination group was given above-mentioned acupuncture and Plantain and Senna Granule. MAIN OUTCOME MEASURES: The defecation cycle, stool property, constipation symptom, accompanying symptoms, gastrointestinal transit time, including total gastrointestinal transit time, mouth-intestine transit time, colonic transit time, right colonic transit time, left colonic transit time and rectosigmoid colonic transit time, and adverse reactions of the three groups were evaluated before treatment, at the end of treatment and 64 weeks after treatment, respectively. RESULTS: Compared with before treatment, the scores of defecation cycle, stool property, constipation symptoms and accompanying symptoms, and gastrointestinal transit time all decreased significantly at the end of treatment in each group (P<0.01), and the combination group showed better results than the other groups (P<0.05). Compared with the end of treatment, the above-mentioned indexes recurred insignificantly in the combination group and acupuncture group after 64 weeks of follow-up (P>0.05), but all recurred significantly in the Plantain and Senna Granule group (P>0.05). Both short- and long-term total response rates of the combination group showed significant differences compared with those of the other two groups (P<0.05 or P<0.01). No serious adverse reactions occurred in all the three groups. CONCLUSION: Acupuncture plus Plantain and Senna Granule can significantly decrease gastrointestinal transit time and defecation cycle in patients with functional constipation; it can also change stool property and alleviate constipation symptom and accompanying symptoms, with good security and tolerance. PMID- 22088587 TI - [Flavonoids of puerarin versus tanshinone II A for ischemic stroke: a randomized controlled trial]. AB - BACKGROUND: Flavonoids are widely used today in the treatment of ischemic stroke. The therapeutic effects and functions of flavonoids are, therefore, generating more and more interest. OBJECTIVE: To investigate the therapeutic effects and functions of flavonoids of puerarin in treating patients with ischemic stroke. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 67 inpatients suffering from ischemic stroke from the Department of Neurology, Changhai Hospital in China were divided into two groups randomly, the treatment group, which was treated with flavonoids of puerarin, and the control group, administered with tanshinone II A sulfate instead. MAIN OUTCOME MEASURES: Defects in neurological function were evaluated according to the National Institutes of Health Stroke Scale (NIHSS) on the first day of onset. Lactate dehydrogenase (LDH), serum interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) levels were determined by radioimmunoassay on the second trial day. After a 14 day treatment, LDH, serum IL-6 and BDNF levels and NIHSS score were also detected, and CT perfusion imaging was used to measure and analyze the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time (MTT). RESULTS: On the first day, NIHSS scores of the two groups were similar. On the second day there was no significant difference in LDH and IL 6 levels between the treatment group and the control group. After a 14-day treatment, LDH and IL-6 levels and the NIHSS score in the treatment group were lower than those in the control group (P<0.05). There was no significant difference in BDNF levels in the two groups. After 14 d, the CT perfusion imaging demonstrated that the treatment group showed more effective blood perfusion than the control group. CONCLUSION: Flavonoids of puerarin can restrain the increase of IL-6 after acute ischemic stroke, and depress the LDH raised by reperfusion after cerebral ischemia. It can also enhance blood perfusion of the ischemic region. PMID- 22088588 TI - [Analysis of facial far-infrared thermogram of patients with acute facial neuritis]. AB - OBJECTIVE: In order to provide an objective observational index for facial neuritis, the authors monitored the changes of facial far-infrared thermogram in patients with acute facial neuritis. METHODS: A total of 23 patients with acute facial neuritis were enrolled from Department of Acupuncture and Moxibustion, Chinese PLA General Hospital. Another 21 healthy participants were selected as the control group. Focal plane thermal imaging system (thermal sensitivity 0.05 degrees centigrade) was applied to collect facial far-infrared thermogram. Temperature differences in the thermogram of both sides of the cheeks, inner canthus, supraorbitals and forehead of the same patient were compared separately and statistically and analyzed by software provided by the imaging system. RESULTS: Results of far-infrared thermography of the patients displayed obvious temperature differences ranging from 0.01 to 0.26 degrees centigrade between two sides of the cheeks, inner canthus, supraorbitals and forehead areas. In the control group, far-infrared thermogram showed that there were no obvious temperature differences between two sides of the cheeks, inner canthus, supraorbitals and forehead. There were significant differences in temperature difference in the four monitoring areas between the two groups (P<0.01). Among the 23 patients, there were 14 patients with congestive change, 7 with ischemic change and 2 with both congestive and ischemic changes. CONCLUSION: The facial far-infrared thermogram of patients with acute facial neuritis is characterized mainly by congestive changes. Far-infrared thermography can objectively reflect the changes of blood-supply status in patients with facial neuritis. PMID- 22088589 TI - [Study of traditional Chinese medicine pulse signals in patients with coronary heart disease based on recurrence quantification analysis]. AB - OBJECTIVE: By using recurrence quantification analysis (RQA) to analyze traditional Chinese medicine pulse signals of patients with coronary heart disease (CHD), this study aims to find nonlinear dynamic parameters of pulses to distinguish patients with CHD from normal subjects. METHODS: First, pulse signals were collected using ZBOX-I pulse digitization gathering analyzer from October 2007 to June 2008. RQA was used to analyze RQA parameters of pulses of 63 patients with CHD and 61 normal subjects. RQA parameters included recurrence rate (RR), determinism (DET), averaged diagonal length (L), entropy of diagonal length (ENTR), length of longest diagonal line (L(max)), laminarity (LAM), trapping time (TT) and length of longest vertical line (V(max)). Then, rank-sum test and BoxPlot were employed to find significant difference and distribution of RQA parameters. Lastly, receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the measurements with significant difference. RESULTS: There were significant differences in RQA parameters of pulse signals between the two groups, including RR, DET, L, ENTR, LAM, TT and V(max), and their areas under the ROC curves were 1.000, 0.898, 0.653, 0.673, 0.885, 0.898, 0.986 and 0.994, respectively. CONCLUSION: Compared with the normal subjects, the pulse signals of the patients with CHD are presented with more certainty, regularity and stability. RQA measurements of RR, TT, Vmax, DET and LAM show good diagnostic value according to their ROC curves. PMID- 22088590 TI - [Analysis of major herbs in Chinese herbal formula Jianpi Huoxue Decoction for improving intestinal permeability based on uniform design]. AB - OBJECTIVE: To investigate the herbal medicines which play a main role in Chinese herbal formula Jianpi Huoxue Decoction for improving intestinal permeability and protect alcohol-induced liver injury and intestine damage, and to explore the analysis method for the material base of pharmacological effects of the Chinese herbal compound. METHODS: Sprague Dawley rats were given Lieber-DeCarli ethanol liquid diet once daily for 6 weeks to induce alcoholic liver injury. In step one, U(17)(17(16)) table of uniform design was adopted to design the experiment and the eight herbs of Jianpi Huoxue Decoction were screened to seek the herbs which play the main role. Three and a half hours before the rats were killed, each rat was administered lipopolysaccharide once, then blood sample was collected from portal vein and endotoxin content in plasma was detected as the index of intestinal permeability. The data were analyzed by stepwise regression to find the herbal drugs which had the best effects and the compatibility ratio of these drugs. In step two, the rats with Lieber-DeCarli liquid diet-induced liver injury were divided into four groups to test and verify the results. RESULTS: According to the obtained regression equation, Rasux Paeonia Alba (Baishao), Rhizoma Alismatis (Zexie) and Fructus Schisandrae Chinensis (Wuweizi) were the main herbal drugs in Jianpi Huoxue Decoction in improving intestinal permeability, and the doses for rats were 1.33, 0.50 and 0.17 g/kg respectively. In the verification experiment, combination of Baishao, Zexie and Wuweizi significantly decreased the endotoxin level in plasma of rats with Lieber-DeCarli-induced liver injury and showed reliability. CONCLUSION: Baishao, Zexie and Wuweizi are the major herbs of Jianpi Huoxue Decoction for improving intestinal permeability. Uniform design is efficient in screening the major herbs or their optimal combination in a certain Chinese compound. PMID- 22088591 TI - [Crohn disease in rats induced by different concentrations of trinitrobenzenesulfonic acid and ethanol]. AB - OBJECTIVE: To induce Crohn disease in rats by intraluminal instillations of different concentrations of 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol. METHODS: Crohn disease in rats was induced with enema containing TNBS and 50% ethanol with volume ratio of 2:1 (experimental group 1) or 1:1 (experimental group 2), or solution containing TNBS and anhydrous ethanol with volume ratio of 2:1 (experimental group 3) or 1:1 (experimental group 4). Equivalent volume of normal saline was used to set as the normal saline control, and rats without any treatment were set as the normal control group. The rats were killed at various time points (3, 7, 14 and 21 d) respectively. Colonic inflammation and damage were assessed microscopically and histologically. RESULTS: In the colon of rats in the experimental group 3, discontinuous erosion, ulceration and infiltration of neutrophils occurred after one week; pebble sign and even segmental inflammation appeared on day 14. On day 21, it appeared improvement in the colon tissue and obviously thickened bowel wall, but the inflammation was easily observed under the light microscope. Experimental group 1 was similar to experimental group 3 in appearance of the colon on days 3 and 7; on day 14, colonic inflammation and damage were improved as compared with the experimental group 3, but there were obvious individual differences in histological findings among rats in group 1. In the experimental group 2, the intestinal wall turned to be normal on day 14. In the experimental group 4, there were high mortality and extensive damage of colon tissues, and the pathological characteristics were quite different from Crohn disease in humans. CONCLUSION: The characteristics of the rat model of Crohn disease induced with a enema containing TNBS and anhydrous ethanol with volume ratio of 2:1 are similar to the clinical features of human Crohn disease, including typical pathological characteristics and long duration of inflammation. It may be an ideal experimental model for studying pathogenesis of Crohn disease and for evaluating treatment effects. PMID- 22088592 TI - [Effects of daidzein on steroid receptor coactivator-1 expression in MC3T3-E1 cells and the mechanism]. AB - OBJECTIVE: To investigate the roles of daidzein in the expressions of steroid receptor coactivator-1 (SRC-1) and nuclear receptor corepressor (NcoR) in MC3T3 E1 osteoblastic cells. METHODS: MC3T3-E1 cells were cultured in alpha-minimal essential medium (alpha-MEM) containing 2% fetal bovine serum and treated with various concentrations of daidzein (10(-9), 10(-7) and 10(-5) mol/L) or 17beta estradiol at 10(-8) mol/L for 3 d. The protein levels of SRC-1 and NcoR in MC3T3 E1 cells were determined by Western blotting. Estrogen receptor (ER) antagonist ICI182780 at 10(-7) mol/L or specific ERalpha antagonist methyl-piperidino pyrazole (MPP) at 10(-6) mol/L were used to block the corresponding receptors, and then MC3T3-E1 cells were treated with daidzein at 10(-7) mol/L or 10(-5) mol/L for 3 d. SRC-1 and NcoR protein levels were detected by Western blotting. RESULTS: The protein levels of SRC-1 increased by 2.5 fold (P<0.05) and 2 fold (P<0.05) by 10(-7) and 10(-5) mol/L of daidzein respectively, while the NcoR levels were not significantly altered. 17beta-Estradiol at dose of 10(-8) mol/L did not affect the expression of SRC-1 but decreased NcoR protein expression by 35% (P<0.05). Compared with the control, daidzein at 10(-7) and 10(-5) mol/L did not increase SRC-1 expression when ERs were blocked by antagonist ICI182780. Daidzein at 10(-7) and 10(-5) mol/L up-regulated SRC-1 by 1.8 fold (P<0.05) and 2.4 fold (P<0.05) respectively while ERalpha was blocked by MPP. CONCLUSION: Daidzein increases protein level of SRC-1 and the ratio of SRC-1/NcoR. ERbeta, instead of ERalpha, participates in the action of daidzein in regulating SRC-1 expression. Up-regulation of SRC-1 and increase of SRC-1/NcoR are part of the mechanism of the estrogenic effect of daidzein in improving osteogenesis. PMID- 22088593 TI - Amelioration of immobilization stress-induced biochemical and behavioral alterations and mitochondrial dysfunction by naringin in mice: possible mechanism of nitric oxide modulation. AB - OBJECTIVE: The present study was undertaken to evaluate the effects of naringin on immobilization stress-induced biochemical-behavioral changes and mitochondrial dysfunction in mice. METHODS: Mice were randomized and grouped based on body weights. Respective drug treatments were given for 14 d, and on the 15th day all the animals were subjected to a 6-hour immobilization stress; then all the animals were subjected to various behavioral paradigms and were sacrificed. Various biochemical parameters and mitochondrial functions were analyzed using brain homogenate. RESULTS: The 6-hour acute immobilization stress significantly altered the behavioral (anxiety and memory) and biochemical parameters coupled with mitochondrial dysfunction in mice. Fourteen days pretreatment with naringin (50 and 100 mg/kg, per oral) significantly inhibited the behavioral and biochemical alterations and mitochondrial dysfunction caused by acute immobilization stress (P<0.05). Further, pretreatment with L-arginine (50 mg/kg, intraperitoneally), a nitric oxide precursor, reversed the protective effect of naringin (P<0.05). In addition, pretreatment with NG-nitro-L-arginine methyl ester (5 mg/kg, intraperitoneally) caused potentiation in the protective effect of naringin. CONCLUSION: These results suggest the possible involvement of nitrergic pathway in the protective effect of naringin against immobilization stress-induced behavioral, biochemical and mitochondrial dysfunctions in mice. PMID- 22088594 TI - 6-gingerol, an active ingredient of ginger, protects acetaminophen-induced hepatotoxicity in mice. AB - OBJECTIVE: To investigate the hepatoprotective efficacy of 6-gingerol against acetaminophen-induced hepatotoxicity in mice. METHODS: Mice were injected with a single dose of acetaminophen (900 mg/kg) to induce hepatotoxicity, while 6 gingerol (30 mg/kg) or the standard drug silymarin (25 mg/kg) was given 30 min after the acetaminophen administration. The mice were sacrificed 4 h after acetaminophen injection to determine the activities of liver marker enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total bilirubin in serum, and lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase and glutathione) in liver homogenate. RESULTS: The treatment of 6-gingerol and silymarin to acetaminophen induced hepatotoxicity showed significant hepatoprotective effect by lowering the hepatic marker enzymes (AST, ALT, and ALP) and total bilirubin in serum (P<0.05). In addition, 6-gingerol and silymarin treatment prevented the elevation of hepatic malondialdehyde formation and the depletion of antioxidant status in the liver of acetaminophen-intoxicated mice (P<0.05). CONCLUSION: The results evidently demonstrate that 6-gingerol has promising hepatoprotective effect which is comparable to the standard drug silymarin. PMID- 22088595 TI - Comparative study on WHO Western Pacific Region and World Federation of Chinese Medicine Societies International Standard Terminologies on Traditional Medicine: six-meridian pattern identification/syndrome differentiation. PMID- 22088596 TI - Introduction of the World Health Organization project of the International Classification of Traditional Medicine. AB - The World Health Organization plans to incorporate "traditional medicine" into the next revision of its International Classification of Diseases-Version 11 (ICD 11). If traditional medicine is included in ICD-11, it is definitely an epoch making issue. The expected result is the International Classification of Traditional Medicine, China, Japan and Korea Version (ICTM-CJK). The intention of the ICTM project is not only beneficial for traditional medical components, but also might be beneficial for Western biomedicine. For this shared purpose, China, Japan and Korea must understand the meaning of this project and collaborate to develop it. PMID- 22088597 TI - Surgical trainee participation during infrainguinal bypass grafting procedures is associated with increased early postoperative graft failure. AB - OBJECTIVE: This study was conducted to determine the potential effect of surgical trainee participation during infrainguinal bypass procedures on postoperative graft patency rates. METHODS: Data from the National Surgical Quality Improvement Program (NSQIP) Participant User Files from 2005 through 2009 were retrospectively reviewed, using propensity score matching, to identify all patients undergoing infrainguinal bypass grafting procedures, excluding those who had prior operation <=30 days of the index procedure. A separate analysis was performed on a subset of procedures from the entire NSQIP sample that was matched on propensity for intraoperative surgical trainee participation. The primary predictor variable was intraoperative surgical trainee participation. The main outcome measure was the 30-day postoperative graft failure rate. RESULTS: For the entire sample of 14,723 NSQIP patients undergoing infrainguinal bypass grafting, 30-day graft failure rates were significantly higher when a surgical trainee participated (5.8%) vs without participation (3.9%; P < .0001). For the cohort of 9234 patients matched on their propensity for intraoperative trainee participation, this difference in graft failure rate remained significant (5.0% with participation vs 4.0% without participation; P = .02). CONCLUSIONS: Surgical trainee participation is an independent risk factor for technical failure after infrainguinal bypass grafting. Prospective evaluation is needed to determine the cause of this increase in graft failure rates for procedures that involve surgical trainees. PMID- 22088598 TI - Selective organ preservation in muscle-invasive bladder cancer: review of the literature. AB - The standard of care for transitional-cell carcinoma of the bladder with invasion to the muscularis propria is radical cystectomy with bilateral pelvic lymph node dissection. However, currently there is a tendency for organ preservation in selected cases of muscle-invasive bladder cancer. Trimodality treatment, including transurethral resection of the bladder tumor (TURBT), radiation therapy and chemotherapy, has been shown to produce 5-year and 10-year overall survival rates comparable to those of radical cystectomy. The current 5-year overall survival rates range from 50 to 67% with trimodality treatment, and approximately 75% of the surviving patients maintains their bladder. After trimodality treatment complete response is obtained in more than 70% of patients with muscle invasive bladder cancer. Clinical criteria helpful in determining patients for bladder preservation include such variables as small tumor size (<2 cm), early tumor stage (T2-T3 disease), a visibly and microscopically complete TURBT, absence of ureteral obstruction, no evidence of pelvic lymph node metastases, and absence of carcinoma in situ (Tis). The close collaboration of urologists, radiation oncologists and medical oncologists is of paramount importance in succeeding in bladder preservation. PMID- 22088599 TI - Clinical significance of plasma CD146 and P-selectin in patients with type 2 diabetic nephropathy. AB - OBJECTIVE: To investigate the levels of plasma CD146 and P-selectin in patients with type 2 diabetic nephropathy at different stages. METHODS: A total of 80 patients with type 2 diabetes mellitus were enrolled in the present study. According to 24h urinary albumin excretion ratio and renal function, they were further divided into group of diabetes without microalbuminuria (DN0, n=20), microalbuminuria group (DN1, n=20), macroalbuminuria group (DN2, n=20) and renal insufficiency group (DN3, n=20). Another 20 healthy subjects were enrolled as control group (non-DM). Plasma CD146 and P-selectin were measured by ELISA. RESULTS: Plasma CD146 and P-selectin were significantly increased in patients with type 2 diabetes with microalbuminuria (DN1) compared with health control (CD146: 415.3+/-29.0 vs. 243.5+/-14.7 ng/ml, P<0.05; P-selectin: 66.8+/-3.4 vs. 45.3+/-2.7 ng/ml, P<0.001). With the development of diabetic nephropathy, both plasma CD146 and P-selectin level progressively rise, with the highest levels in patients with significant renal insufficiency (DN3: 515.9+/-36.9 and 81.5+/-5.1 ng/ml respectively, P<0.001). Moreover, the increase in CD146 is positively co related to the rise of P-selectin in patients with type 2 diabetes. CONCLUSION: Expression of CD146 and P-selectin in patients with type 2 diabetes is elevated, and they are positively correlated with severity of diabetic nephropathy. PMID- 22088600 TI - The design and recombinant protein expression of a consensus porcine interferon: CoPoIFN-alpha. AB - CoPoIFN-alpha is a recombinant non-naturally occurring porcine interferon-alpha (IFN-alpha). It was designed by scanning 17 porcine IFN-alpha nonallelic subtypes and assigning the most frequently occurring amino acid in each position. We used a porcine IFN-alpha (PoIFN-alpha) derived from domestic pig as a control. Both porcine IFN-alpha genes were introduced into yeast expression vector PpICZalpha-A and expressed in Pichia pastoris. The antiviral unit of these two IFN-alphas were assayed in MDBK, PK-15 and MARC-145 cells against vesicular stomatitis virus (VSV), and their inhibitory abilities on pseudorabies virus (PRV) and porcine reproductive and respiratory syndrome virus (PRRSV) replication were also examined, respectively. We found the antiviral activity (units/mg) of CoPoIFN alpha was 46.4, 63.6 and 53.5-fold higher than that of PoIFN-alpha for VSV inhibition in MDBK, PK-15 and MARC-145 cells, 4.8-fold higher for PRV inhibition in PK-15 cells, and 5-fold higher for PRRSV inhibition in MARC-145 cells. Our results also showed that the PRV and PRRSV-specific cytopathic effect (CPE) could be inhibited in the cells pretreated with CoPoIFN-alpha and PoIFN-alpha, and the virus titers in the cells pretreated with CoPoIFN-alpha were lower than those cells pretreated with PoIFN-alpha by 10-20-fold. The antiproliferative activity of CoPoIFN-alpha was significantly higher than that of PoIFN-alpha on a molar basis. The mRNA level of Mx1 and OAS1 genes in PK-15 cells induced by CoPoIFN alpha were enhanced about 4.6-fold and 3.2-fold compared to that induced by PoIFN alpha. Based on a homology model of CoPoIFN-alpha and IFNAR2, all of the different residues between native PoIFN-alpha and CoPoIFN-alpha were not involved in IFNAR1 binding site, and there is no direct interaction between these residues and IFNAR2, either. We speculate that the higher activity of CoPoIFN-alpha was likely due to the electrostatic potential introduced by residue Arg156 around the binding site or a structural perturbation caused by these different residues. This may enhance the overall binding affinity of CoPoIIFN-alpha and the receptors. Thus, CoPoIFN-alpha may have the potential to be used in therapy of porcine diseases. PMID- 22088601 TI - Preparing the ground for the 'paperless hospital': a case study of medical records management in a UK outpatient services department. AB - PURPOSE: The purpose of the study was to understand the preparations for the introduction of electronic patient record systems (EPRs) within the outpatient services department of a large acute hospital based in the UK. In particular, one of the main aims of the study was to examine in detail the likely impact of EPRs on the working practices of healthcare workers, their expectations regarding the impact of EPRs within the department and other sociotechnical aspects of the management of patient information. METHODS: Twenty-seven semi-structured interviews were undertaken with staff in a variety of roles that deal with the management of medical records. The interviews focused on the organisation of the medical records department and current problems (e.g., missing records). In addition, the interviews contained questions about the specific role of medical records supervisors in the administration of records, as well as pathways and expectations about EPRs more generally. The data from the interviews was analysed using a mixture of thematic and template analysis and coded using constructs from a sociotechnical model of information system implementation and adoption. RESULTS: The findings show that despite severe delays to the nationally led (NPfIT) roll-out of EPRs and associated IT infrastructure within the UK, staff attitudes within the department were broadly positive about the potential of future EPRs to deliver efficiencies (e.g., improved workflow within the department, reduced reliance on paper-based systems). One of the main influences on attitudes towards the type of EPRs that should exist within outpatients was prompted by negative reactions to the way in which NPfIT systems had been managed and attempted to be introduced in the past. A strong commitment to end-user involvement in EPRs design, together with a rejection of NPfIT, appears to have shaped attitudes towards future expectations of the adoption of new EPRs within the department. In addition, staff do not believe that a rapid change to 'paperless' working is likely to be possible. CONCLUSIONS: Our findings provide further evidence that there is a need to treat the implementation of EPRs not simply as an exercise in technical system delivery, but as a larger process of sociotechnical systems change. We conclude the paper with some guidelines, the aim of which is to provide guidance regarding EPRs implementation and adoption informed by sociotechnical principles and ideas. PMID- 22088602 TI - Unidentified bright objects in neurofibromatosis type 1: conventional MRI in the follow-up and correlation of microstructural lesions on diffusion tensor images. AB - PURPOSE: To evaluate the evolution of unidentified bright objects (UBOs) in individuals with neurofibromatosis type 1 (NF1) by serial magnetic resonance imaging (MRI), and to relate this to regional fractional anisotropy (FA). MATERIALS AND METHODS: The signal pattern of the T2-weighted sequences in the basal ganglia, thalamus, brain stem, and cerebellum for 27 NF1 individuals and a control group were analyzed by diffusion tensor imaging (DTI). The presence or absence of UBOs in 2 consecutive MRI examinations was related to FA. RESULTS: We demonstrated significant differences in FA for the basal ganglia, cerebellum, and thalamus between NF1 patients and controls (P <= 0.05), even with a reduction or disappearance of UBOs. CONCLUSIONS: MRI allows for adequate monitoring of the temporal and spatial distribution of UBOs in patients with NF1. DTI confirmed changes in FA despite the disappearance or reduction of UBOs, thereby confirming the hypothesis that microstructural damage occurs in specific brain regions of NF1 patients. PMID- 22088603 TI - Psychological distress in a Department of Veterans Affairs spine patient population. AB - BACKGROUND CONTEXT: The veteran population presents a unique confluence of biopsychosocial factors in the treatment of spinal conditions. In addition to poorer health status and higher numbers of chronic medical conditions compared with the general population, previous reports have highlighted the high prevalence of psychological disorders within the Department of Veterans Affairs (VA) health system. To our knowledge, no study has specifically evaluated psychological distress in patients with a spinal disorder within the VA health system. PURPOSE: To determine the prevalence of psychological distress among spine patients in a VA hospital and if higher levels of distress correlated with patient demographics and self-reported patient outcome scores. STUDY DESIGN/SETTING: Cross-sectional evaluation of adult patients at a regional VA outpatient orthopedic spine surgery clinic. PATIENT SAMPLE: One hundred forty nine adult patients presenting for treatment of spine-related disorders. OUTCOME MEASURES: Patients were evaluated using the Distress and Risk Assessment Method (DRAM), a validated survey consisting of the Zung Depression Scale and the Modified Somatic Perception Questionnaire. In addition, self-reported pain, disability, and quality of life were assessed using the visual analog scale (VAS) for neck or back pain and the Neck Disability Index or Oswestry Disability Index (ODI) depending on the patient's location of pain. METHODS: The DRAM survey was used to determine the prevalence of psychological distress by classifying patients into normal, at-risk, and severe distress groups. Visual analog scale scores for neck and back pain, and self-reported disability scores, and demographic data including age, gender, combat experience, and use of antidepressant, anxiolytic, or narcotic medications were obtained at the time of enrollment. RESULTS: The DRAM survey identified 79.9% of patients as having some degree of psychological distress, whereas the remaining 20.1% were classified as normal. Among those with psychological distress, 43.6% of patients were categorized as severe distress. Compared with the normal group, a history of combat was more frequent in all distressed patient groups including the at-risk (p=.04) and severe distress (p=.009) groups. Those in the severe distress category more commonly reported the use of narcotics (p=.043) and antidepressant/anxiolytics medications (p=.0001). Those in the severe distress group had significantly higher ODI scores (p<.0001) and back pain VAS scores (p=.0360) compared with the normal group. CONCLUSIONS: We identified a large number of patients (80%) with some level of psychological distress and 43% with severe distress. The percent of patients with severe psychological distress in the VA was double that previously reported in a non-VA patient setting. Patients with severe distress had higher ODI scores, back pain VAS scores, use of narcotics and antidepressants, and a reported history of combat when compared with those without distress. PMID- 22088604 TI - RETRACTED: A study of shower aerosols and deposition of lead dust from distribution system and premise plumbing in Baltimore homes. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 22088605 TI - Effects of coenzyme Q10 on vascular endothelial function in humans: a meta analysis of randomized controlled trials. AB - OBJECTIVE: The purpose of this study was to quantify the effect of coenzyme Q10 on arterial endothelial function in patients with and without established cardiovascular disease. BACKGROUND: Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis. METHODS AND RESULTS: The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 July 2011. Eligible studies were randomized controlled trials on the effects of coenzyme Q10 compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Five eligible trials enrolled a total of 194 patients. Meta-analysis using random-effects model showed treatment with coenzyme Q10 significantly improvement in endothelial function assessed peripherally by flow-mediated dilatation (SMD 1.70, 95% CI: 1.00-2.4, p<0.0001). However, the endothelial function assessed peripherally by nitrate-mediated arterial dilatation was not significantly improved by using fix effects model (SMD -0.19, 95% CI: -1.75 to 1.38, p = 0.81). CONCLUSION: Coenzyme Q10 supplementation is associated with significant improvement in endothelial function. The current study supports a role for CoQ10 supplementation in patients with endothelial dysfunction. PMID- 22088606 TI - Candida theae sp. nov., a new anamorphic beverage-associated member of the Lodderomyces clade. AB - Four strains representing a novel yeast species belonging to the genus Candida were independently isolated in Taiwan and Ecuador. Two strains (G17(T) and G31) were isolated in Taiwan, by pellet precipitation from plastic-bottled tea drinks produced in Indonesia, while two additional strains (CLQCA 10-049 and CLQCA 10 062) were recovered from ancient chicha fermentation vessels found in tombs in Quito, Ecuador. These four strains were morphologically, and phylogenetically identical to each other. No sexual reproduction was observed on common sporulation media. Large-subunit (LSU) rRNA gene sequence analysis revealed the four strains to belong to the Lodderomyces clade, closely related to members of the Candida parapsilosis species complex. The four strains, which have identical LSU D1/D2 sequences, differ from their closest phylogenetic neighbors, Candida orthopsilosis and Candida parapsilosis, by 6-9 nt substitutions, respectively. Physiologically, the four strains are similar to Candida parapsilosis, although they can be distinguished from their closest relative by the assimilation of arbutin, nitrite, and creatine. The Indonesian and Ecuadorian strain sets can also be distinguished from one another based on ITS sequencing, differing by 4 substitutions in ITS1 and 1 single nucleotide indel in ITS2. Collectively, the results indicate that the four strains represent a previously unrecognized species of Candida. The name Candida theae sp. nov. is proposed to accommodate these strains, with G-17(T) (BCRC 23242(T)=CBS 12239(T)=ATCC MYA-4746(T)) designated as the type strain. PMID- 22088607 TI - Response styles to depressed mood affect the long-term course of psychosocial functioning in depressed patients. AB - BACKGROUND: Components of psychosocial functioning represent both relevant mental health outcomes and predictors for the further course of illness in patients with depression and other mental illnesses. Determinants of these outcomes beyond residual symptom levels have rarely been investigated. The present study aimed at investigating prospective effects of demographic variables, depression levels, and response styles to depressed mood on future psychosocial functioning outcomes in depressed patients. METHODS: We followed up a sample of unipolar depressed inpatients (n=71) one, six, 42, and 66 months after hospital discharge. At each measuring point, patients were assessed with regard to diagnostic status, symptom levels, response styles, subjective quality of life (QoL), and interviewer-rated social and occupational functioning. Longitudinal data were analyzed using time lagged linear models. RESULTS: Controlled for age, sex, and concurrent depression levels, higher symptom-focused rumination predicted lower future QoL in the psychological domain and lower social and occupational functioning. In parallel, higher levels of habitual distraction predicted higher future QoL in the psychological domain. Effects were comparable for men and women. CONCLUSION: Given that response styles to depressed mood appear not only to affect the course of depressive symptoms but also future psychosocial outcomes, it is of particular relevance to address these coping styles in psychological therapies for depression and high-risk groups. Future controlled intervention studies should investigate possible specific mechanisms of how response styles may affect psychosocial outcomes. PMID- 22088608 TI - A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder. AB - BACKGROUND: Recurrent-episode Major Depressive Disorder (MDD) is associated with a number of neuropsychological deficits. To date, less is known about whether these are present in the first-episode. The current aim was to systematically evaluate the literature on first-episode MDD to determine whether cognition may be a feasible target for early identification and intervention. METHODS: Electronic database searches were conducted to examine neuropsychological studies in adults (mean age greater than 18 years old) with a first-episode of MDD. Effect sizes were pooled by cognitive domain. Using meta-regression techniques, demographic and clinical factors potentially influencing heterogeneity of neuropsychological outcome were also investigated. RESULTS: The 15 independent samples reviewed yielded data for 644 patients with a mean age of 39.36 years (SD=10.21). Significant cognitive deficits were identified (small to medium effect sizes) for psychomotor speed, attention, visual learning and memory, and all aspects of executive functioning. Symptom remission, inpatient status, antidepressant use, age and educational attainment, each significantly contributed to heterogeneity in effect sizes in at least one cognitive domain. LIMITATIONS: Reviewed studies were limited by small sample sizes and often did not report important demographic and clinical characteristics of patients. CONCLUSIONS: The current meta-analysis was the first to systematically demonstrate reduced neuropsychological functioning in first-episode MDD. Psychomotor speed and memory functioning were associated with clinical state, whereas attention and executive functioning were more likely trait-markers. Demographic factors were also associated with heterogeneity across studies. Overall, cognitive deficits appear to be feasible early markers and targets for early intervention in MDD. PMID- 22088609 TI - Pain anxiety, acceptance, and outcomes among individuals with HIV and chronic pain: a preliminary investigation. AB - The current study investigated the role of during treatment changes in pain anxiety in the relation between during treatment changes in pain acceptance and chronic pain outcomes. Participants included 45 (15 women) adults (M(age) = 50.42, SD = 7.69) who were HIV positive and experienced chronic pain. They were offered 12 weekly, 90-min group CBT sessions to increase understanding about chronic pain and to improve coping skills. Four hierarchical regression analyses were conducted to examine the mediating role of treatment changes in pain anxiety in the relation between treatment changes in pain acceptance and chronic pain outcomes. Results suggest that increases in pain acceptance during treatment were associated with decreased levels of pain anxiety during treatment, as well as decreases in pain-related impairment at treatment completion. Furthermore, decreases in pain anxiety during treatment were associated with decreases in pain related impairment at treatment completion. Finally, treatment changes in pain anxiety were found to partially mediate the association between treatment changes in pain acceptance and pain-related impairment at treatment completion. Results are discussed within the context of better understanding the processes of change within a CBT model for chronic pain patients. PMID- 22088610 TI - Effect of self-focused attention on post-event processing in social anxiety. AB - The study investigated the relationship between self-focused attention (SFA) and post-event processing (PEP) in social anxiety. SFA is the process of directing attention to internal stimuli during a social interaction. PEP is a detailed review of performance following an interaction. Highly socially anxious students (N = 82) were randomly assigned to a high SFA (n = 40) or low SFA condition (n = 42) and completed baseline measures of social anxiety, depression, trait SFA, and trait rumination. After SFA was manipulated via instructions, participants engaged in a 5-min unstructured conversation with a confederate, followed by a manipulation check. PEP was assessed the next day online. The high SFA group reported a similar amount of positive PEP but more frequent negative PEP over the 24-h period compared to the low SFA group. These results provide support for a causal relationship between SFA and PEP and have important applications for the development of effective cognitive-behavioural interventions. PMID- 22088611 TI - Anxiety and depression and their links with delusions and hallucinations in people with a dual diagnosis of psychosis and substance misuse: a study using data from a randomised controlled trial. AB - Rates of depression and anxiety have been linked to severity and distress associated with positive symptoms in psychosis. There is also tentative evidence to suggest that these concurrent symptoms might be related to delusional and hallucinatory content. Our aim was to assess the cross-sectional associations between anxiety and depression, and hallucination and delusion severity and distress in a sample of 327 people dually diagnosed with psychosis and substance misuse problems. In addition, the relationships between specific symptom content and levels of anxiety and depression were examined. Anxiety was associated with delusion distress and depression with hallucination distress, although neither was related to symptom severity. Auditory commands to harm or kill the self were associated with higher levels of depression. Delusions with themes pertaining to the paranormal, and those with references to celebrities were associated with lower levels of depression. No specific delusion or hallucination content was associated with level of anxiety, when other variables were controlled for. The results demonstrate that anxiety and depression are linked to distinct aspects of psychotic experience, highlighting the need to acknowledge the role of these concurrent symptoms in the context of psychosis. In addition, findings relating to specific types of delusions and hallucinations highlight avenues for further research. PMID- 22088612 TI - Interaction between filaggrin null mutations and tobacco smoking in relation to asthma. AB - BACKGROUND: The mechanisms underlying the association between filaggrin (FLG) deficiency and asthma are not known. It has been hypothesized that FLG deficiency leads to enhanced percutaneous exposure to environmental substances that might trigger immune responses. We hypothesized that interactions between FLG deficiency and environmental exposures play a role in asthma development. OBJECTIVE: We sought to investigate possible interactions between FLG null mutations and tobacco smoking in relation to asthma. METHODS: A total of 3471 adults from a general population sample participated in a health examination. Lung function and serum specific IgE levels to inhalant allergens were measured, and information on asthma and smoking was obtained by means of questionnaire. Participants were genotyped for the 2 most common FLG null mutations in white subjects: R501X and 2282del4. Another Danish population was used for replication. RESULTS: The FLG null mutation genotype was significantly associated with a higher prevalence of asthma and decreased FEV(1)/forced vital capacity ratio. In logistic regression analyses with asthma as the outcome, a significant interaction was found between FLG null mutations and smoking status (P = .02). This interaction was confirmed, although it was not statistically significant, in another Danish population study. Interactions between FLG genotype and cumulated smoking exposure were found in relation to asthma (P = .03) and decreased FEV(1)/forced vital capacity ratio (P = .03). A 3-way interaction was found among FLG genotype, smoking, and asthma, suggesting that the FLG-smoking interaction mainly played a role in nonatopic subjects. CONCLUSION: FLG null mutations modified the effects of smoking on the risk of asthma. This finding might have implications for risk stratification of the population. PMID- 22088615 TI - The conceptualization and measurement of individualized care. AB - Individualized nursing care, a form of person-centered care delivery, is accepted as best practice, yet its implementation into actual care is far from complete. Appropriate measures of this elusive concept are needed to better understand barriers to implementation. This study explored and tested the convergent validity and the reliability of 2 individualized nursing care measures. A cross sectional survey design was used to collect data using the Individualized Care Scale and the Individualized Care Instrument (ICI) from a sample of nurses (n = 263, response rate 71%) working in older peoples' care settings in Finland, and the data were analyzed statistically. Cronbach's alpha coefficients for the ICI scales (.63-.80) and ICS-A and B subscales (both alpha = .91) demonstrated only moderate correlation between the 2 instruments (r = -.39 to .50) and possibly the complexity of measuring "individualized care." The study acknowledges the latent influence of culture and care approach to the conceptualization of individuality. It concludes that the concept may best be measured at this point with the use of other factors in addition to instruments to capture its multiple domains. PMID- 22088613 TI - Toll-like receptor 4-, 7-, and 8-activated myeloid cells from patients with X linked agammaglobulinemia produce enhanced inflammatory cytokines. AB - BACKGROUND: Bruton tyrosine kinase (BTK) is a component of signaling pathways downstream from Toll-like receptors (TLRs) 2, 4, 7, 8, and 9. Previous work in BTK-deficient mice, cell lines, and cultured cells from patients with X-linked agammaglobulinemia (XLA) suggested defective TLR-driven cytokine production. OBJECTIVE: We sought to compare TLR-4-, TLR-7-, and TLR-8-induced cytokine production of primary cells from patients with XLA with that seen in control cells. METHODS: PBMCs from patients with XLA, freshly isolated plasmacytoid dendritic cells, monocytes, and monocytoid dendritic cells were activated with TLR-4, TLR-7, and TLR-8 agonists. Signaling intermediates and intracellular and secreted cytokine levels were compared with those seen in control cells. RESULTS: Although TLR-4, TLR-7, and TLR-8 activation of nuclear factor kappaB and mitogen activated protein kinase pathways in cells from patients with XLA and control cells were comparable, TLR-activated freshly isolated monocytes and monocytoid dendritic cells from patients with XLA produced significantly more TNF-alpha, IL 6, and IL-10 than control cells. TLR-7/8-activated plasmacytoid dendritic cells produced normal amounts of IFN-alpha. In murine models BTK regulates the degradation of Toll-IL-1 receptor domain-containing adaptor protein, terminating TLR-4-induced cytokine production. Although this might explain the heightened TLR 4-driven cytokine production we observed, Toll-IL-1 receptor domain-containing adaptor protein degradation is intact in cells from patients with XLA, excluding this explanation. CONCLUSION: In contrast to previous studies with BTK-deficient mice, cell lines, and cultured cells from patients with XLA suggesting impaired TLR-driven cytokine production, these data suggest that BTK inhibits TLR-induced cytokine production in primary human cells. PMID- 22088614 TI - Bifidobacterium as an oral delivery carrier of interleukin-12 for the treatment of Coxsackie virus B3-induced myocarditis in the Balb/c mice. AB - IL-12 plays an important role in the treatment of many infectious diseases by being administered intravenously or intramuscularly. However, intravenous or intramuscular administration is difficult and inconvenient and may cause side effects. The aim of this study is to develop a novel oral delivery system for IL 12 using genetically engineered Bifidobacterium longum as the carrier and further investigate the efficacy of IL-12-expressed B. longum on the coxsackie virus B3 (CVB3)-induced myocarditis in mice. A mIL-12 gene expression vector pBBADs-IL-12 for B. longum was constructed and transformed into Bifidobacterium. Subsequently, the expression of mIL-12 in the engineered B. longum was identified in vitro by western blot and enzyme-linked immunosorbent assay (ELISA) after l-arabinose induction. Moreover, our data indicated that oral administration of IL-12 expressed B. longum for two weeks after CVB3 infection in the Balb/c mice could downregulate the severity of virus-induced myocarditis, markedly reduce the virus titers in the heart and induce a Th1 pattern in the spleen and heart compared with the controls. In conclusion, a novel oral delivery system of Bifidobacterium for murine IL-12 has been successfully established. Oral administration of mIL-12 transformed B. longum may play a therapeutic role in the treatment of CVB3 induced myocarditis in the mice. PMID- 22088616 TI - Detection of Toxoplasma gondii antigens reactive with antibodies from serum, amniotic, and allantoic fluids from experimentally infected pregnant ewes. AB - Toxoplasma gondii, an intracellular protozoan parasite, is one of the major causes of infectious abortion in sheep. To further understand the pathogenesis of toxoplasmosis, serum, amniotic and allantoic fluids and foetal stomach contents were collected from experimentally infected pregnant ewes to determine pathogen numbers and other markers of infection. Fifteen pregnant ewes (90 days of gestation) were each orally inoculated with 3000 sporulated oocysts of T. gondii. Serum samples were collected weekly following challenge. Amniotic and allantoic fluids and foetal stomach contents were collected at 21, 25, 28, 33 and 35 days post-infection. Characteristic placental lesions were detected in 1 of 4 challenged ewes at day 25, 3 of 4 challenged ewes at day 28 and in all challenged ewes at days 33 and 35 post-infection. T. gondii was detected only sporadically in amniotic and allantoic fluids before 35 days of infection, by real-time PCR, and only in ewes with placental lesions. At 35 days post-infection, high numbers of parasite were detected in both amniotic and allantoic fluids. An increase in the number of fluids from challenged animals with IgM and IgG was detected over time, except for IgG in allantoic fluid, which was detected in all samples from day 21 post-infection. IgG in amniotic and allantoic fluids was shown to be specific for T. gondii, and reacted with antigens with an apparent molecular mass of approximately 22 kDa and 30 kDa. Results suggest a maternal source of immunoglobulin in the allantoic fluid and a foetal source of immunoglobulin in the amniotic fluid early in infection but that both sources may contribute immunoglobulin to both fluids at a later stage. PMID- 22088617 TI - Estimation of the risk of conversion of mild cognitive impairment of Alzheimer type to Alzheimer's disease in a south Brazilian population-based elderly cohort: the PALA study. AB - BACKGROUND: Higher mild cognitive impairment (MCI) prognostic variability has been related to sample characteristics (community-based or specialized clinic) and to diverse operationalization criteria. The aim of the study was to evaluate the trajectory of MCI of Alzheimer type in a population-based elderly cohort in Southern Brazil. We also estimated the risk for the development of probable Alzheimer's disease (AD) in comparison with healthy subjects. METHODS: Data were derived from a population-based cohort (the PALA study). MCI outcomes were sub classified into three categories: conversion, stabilization, and reconversion. The risk of progression to dementia was compared between MCI and normal participants. The analysis was based on 21 MCI subjects and 220 cognitively intact participants (N = 241). RESULTS: Of the 21 MCI subjects, 38% developed dementia, 24% remained stable and 38% improved. The MCI annual conversion rate to AD was 8.5%. MCI was associated with significantly higher risk of conversion to AD (HR = 49.83, p = 0.004), after adjustment for age, education, sex and Mini Mental State Examination score. CONCLUSIONS: Independent of the heterogeneity of the outcomes, MCI of the Alzheimer type participants showed significantly higher risk of developing probable AD, demonstrating the impact of the use of these MCI criteria that emphasize long-term episodic memory impairment. PMID- 22088618 TI - Pathophysiology of acute respiratory distress syndrome. Glucocorticoid receptor mediated regulation of inflammation and response to prolonged glucocorticoid treatment. AB - Based on molecular mechanisms and physiologic data, a strong association has been established between dysregulated systemic inflammation and progression of ARDS. In ARDS patients, glucocorticoid receptor-mediated down-regulation of systemic inflammation is essential to restore homeostasis, decrease morbidity and improve survival and can be significantly enhanced with prolonged low-to-moderate dose glucocorticoid treatment. A large body of evidence supports a strong association between prolonged glucocorticoid treatment-induced down-regulation of the inflammatory response and improvement in pulmonary and extrapulmonary physiology. The balance of the available data from controlled trials provides consistent strong level of evidence (grade 1B) for improving patient-centered outcomes. The sizable increase in mechanical ventilation-free days (weighted mean difference, 6.58 days; 95% CI, 2.93 -10.23; P<0.001) and ICU-free days (weighted mean difference, 7.02 days; 95% CI, 3.20-10.85; P<0.001) by day 28 is superior to any investigated intervention in ARDS. The largest meta-analysis on the subject concluded that treatment was associated with a significant risk reduction (RR=0.62, 95% CI: 0.43-0.91; P=0.01) in mortality and that the in-hospital number needed to treat to save one life was 4 (95% CI 2.4-10). The balance of the available data, however, originates from small controlled trials with a moderate degree of heterogeneity and provides weak evidence (grade 2B) for a survival benefit. Treatment decisions involve a tradeoff between benefits and risks, as well as costs. This low cost highly effective therapy is familiar to every physician and has a low risk profile when secondary prevention measures are implemented. PMID- 22088619 TI - [Management of goiters]. AB - Simple goiter is defined as an enlarged thyroid without dysfunction, thyroiditis or cancer. Complications of the goiter appear only at stage of plurinodulaire goiter. Homogeneous simple goiters of young subjects resolve with thyroid hormone administration. Many simple multinodular goiters of adults can benefit from simple monitoring. Total thyroidectomy is recommended for goiters that become symptomatic, unsightly, accompanied by lowering of TSH concentration, or containing suspicious nodules. Radioactive iodine constitutes an alternative to surgery for voluminous, compressive, hyperfunctionnal goiters, especially in older people. PMID- 22088622 TI - Re: the effect of tumor location on prognosis in patients treated with radical nephroureterectomy at memorial sloan-kettering cancer center. PMID- 22088623 TI - Re: chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy. PMID- 22088620 TI - IRF5 haplotypes demonstrate diverse serological associations which predict serum interferon alpha activity and explain the majority of the genetic association with systemic lupus erythematosus. AB - OBJECTIVE: High serum interferon alpha (IFNalpha) activity is a heritable risk factor for systemic lupus erythematosus (SLE). Auto-antibodies found in SLE form immune complexes which can stimulate IFNalpha production by activating endosomal Toll-like receptors and interferon regulatory factors (IRFs), including IRF5. Genetic variation in IRF5 is associated with SLE susceptibility; however, it is unclear how IRF5 functional genetic elements contribute to human disease. METHODS: 1034 patients with SLE and 989 controls of European ancestry, 555 patients with SLE and 679 controls of African-American ancestry, and 73 patients with SLE of South African ancestry were genotyped at IRF5 polymorphisms, which define major haplotypes. Serum IFNalpha activity was measured using a functional assay. RESULTS: In European ancestry subjects, anti-double-stranded DNA (dsDNA) and anti-Ro antibodies were each associated with different haplotypes characterised by a different combination of functional genetic elements (OR>2.56, p<1.9*10(-14) for both). These IRF5 haplotype-auto-antibody associations strongly predicted higher serum IFNalpha in patients with SLE and explained >70% of the genetic risk of SLE due to IRF5. In African-American patients with SLE a similar relationship between serology and IFNalpha was observed, although the previously described European ancestry-risk haplotype was present at admixture proportions in African-American subjects and absent in African patients with SLE. CONCLUSIONS: The authors define a novel risk haplotype of IRF5 that is associated with anti-dsDNA antibodies and show that risk of SLE due to IRF5 genotype is largely dependent upon particular auto-antibodies. This suggests that auto antibodies are directly pathogenic in human SLE, resulting in increased IFNalpha in cooperation with particular combinations of IRF5 functional genetic elements. SLE is a systemic autoimmune disorder affecting multiple organ systems including the skin, musculoskeletal, renal and haematopoietic systems. Humoral autoimmunity is a hallmark of SLE, and patients frequently have circulating auto-antibodies directed against dsDNA, as well as RNA binding proteins (RBP). Anti-RBP autoantibodies include antibodies which recognize Ro, La, Smith (anti-Sm), and ribonucleoprotein (anti-nRNP), collectively referred to as anti-retinol-binding protein). Anti-retinol-binding protein and anti-dsDNA auto-antibodies are rare in the healthy population. These auto-antibodies can be present in sera for years preceding the onset of clinical SLE illness and are likely pathogenic in SLE. PMID- 22088624 TI - Re: impact of patient age on outcome following bladder-preserving treatment for non-muscle-invasive bladder cancer. PMID- 22088626 TI - Re: Pathological Stage Review is Indicated in Primary pT1 Bladder Cancer. PMID- 22088627 TI - Re: Expression Signature of E2F1 and its Associated Genes Predict Superficial to Invasive Progression of Bladder Tumors. PMID- 22088629 TI - Re: does perineural invasion on prostate biopsy predict adverse prostatectomy outcomes? PMID- 22088631 TI - Re: The Gleason Score of Tumor at the Margin in Radical Prostatectomy is Predictive of Biochemical Recurrence. PMID- 22088632 TI - Re: continence, potency and oncological outcomes after robotic-assisted radical prostatectomy: early trifecta results of a high-volume surgeon. PMID- 22088634 TI - Re: chlorhexidine rinse for prevention of urethritis in men linked to oral sex. PMID- 22088633 TI - Re: management of prostate cancer in older men: recommendations of a working group of the International Society of Geriatric Oncology. PMID- 22088635 TI - Re: metabolism of fructose to oxalate and glycolate. PMID- 22088636 TI - Re: diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation. PMID- 22088637 TI - Re: Determination of Renal Stone Composition With Dual-Energy CT: In Vivo Analysis and Comparison With X-Ray Diffraction. PMID- 22088638 TI - Re: results of buccal mucosa grafts for repairing long bulbar urethral strictures. PMID- 22088639 TI - Re: the impact of lower urinary tract symptoms and urinary incontinence on female sexual dysfunction using a validated instrument. PMID- 22088640 TI - Re: antibacterial therapy improves the effectiveness of prostate cancer detection using prostate-specific antigen in patients with asymptomatic prostatitis. PMID- 22088641 TI - Re: effect of transurethral resection of the prostate on erectile function: a prospective comparative study. PMID- 22088642 TI - Re: revascularization versus medical therapy for renal-artery stenosis. PMID- 22088646 TI - Re: treatment of 161 men with symptomatic late onset hypogonadism with long acting parenteral testosterone undecanoate: effects on body composition, lipids, and psychosexual complaints. PMID- 22088647 TI - Re: distribution of male infertility specialists in relation to the male population and assisted reproductive technology centers in the United States. PMID- 22088648 TI - Re: clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. PMID- 22088649 TI - Re: adverse effect of paroxetine on sperm. PMID- 22088650 TI - Re: relationship between semen parameters and spontaneous pregnancy. PMID- 22088651 TI - Re: ovarian tissue autologous transplantation to the upper extremity for girls receiving abdominal/pelvic radiation: 20-year follow-up of reproductive endocrine function. PMID- 22088653 TI - Re: congenital juvenile granulosa cell tumor of the testis in newborns. PMID- 22088654 TI - Re: therapeutic potential of human mesenchymal stem cells producing IL-12 in a mouse xenograft model of renal cell carcinoma. PMID- 22088655 TI - Atypical frontal lobe activity during verbal working memory in youth with a family history of alcoholism. AB - BACKGROUND: Abnormal brain functioning during verbal working memory (VWM) tasks has been shown in individuals with alcohol use disorders (AUDs). Since adolescents with a familial history of alcoholism (FHP) are at high risk for developing an AUD, it is important to consider whether atypical brain activity during VWM may help to explain FHP vulnerability toward developing alcoholism. METHODS: To that end, using functional magnetic resonance imaging, we examined brain response during a VWM 2-back task in 19 FHP adolescents and 16 age and gender-matched family history negative (FHN) controls. RESULTS: Despite no group differences in task accuracy, FHP youth had significantly slower average reaction time when making correct responses during the 2-back condition than FHN youth. In contrast to a vigilance control condition, while covarying for reaction time, FHP adolescents showed less activation during VWM than FHN youth in multiple areas of the prefrontal cortex (PFC)--a brain region crucial to intact working memory skills. CONCLUSIONS: These results suggest that even prior to heavy alcohol use, FHP adolescents show atypical executive brain functioning during VWM, and that these differences are independent of slower working memory reaction time in FHP youth. Given the importance of working memory in numerous areas of day-to-day functioning, such as adaptive decision-making, these abnormalities may contribute to FHP youth vulnerability toward developing AUDs. PMID- 22088657 TI - Excess CO2 supply inhibits mixotrophic growth of Chlorella protothecoides and Nannochloropsis salina. AB - Mixotrophy can be exploited to support algal growth over night or in dark-zones of a photobioreactor. In order to achieve the maximal productivity, however, it is fundamental also to provide CO(2) in excess to maximize photosynthetic activity and phototropic biomass production. The aim of this paper is to verify the possibility of exploiting mixotrophy in combination with excess CO(2). Two species with high biomass productivity were selected, Nannochloropsis salina and Chlorella protothecoides. Different organic substrates available at industrial scale were tested, and glycerol chosen for its ability to support growth of both species. In mixotrophic conditions, excess CO(2) stimulated photosynthesis but blocked the metabolization of the organic substrate, thus canceling the advantages of mixotrophy. By cultivating microalgae under day-night cycle, organic substrate supported growth during the night, but only if CO(2) supply was not provided. This represents thus a possible method to reconcile CO(2) stimulation of photosynthesis with mixotrophy. PMID- 22088656 TI - Psychological processes and stimulant use among men who have sex with men. AB - BACKGROUND: Prior research established that psychological factors are associated with the frequency of stimulant (i.e., cocaine, crack, and methamphetamine) use among substance-using men who have sex with men (MSM). The present investigation examined whether and how psychological factors are associated with engagement in any stimulant use in the broader population of MSM. METHODS: A probability sample of 879 MSM residing in San Francisco was obtained using random digit dialing from May of 2002 through January of 2003. Of these, 711 participants (81%) completed a mail-in questionnaire that assessed psychological factors and substance use. After accounting for demographic factors, a multiple logistic regression analysis examined correlates of any self-reported stimulant use during the past 6 months. Path analyses examined if the use of alcohol or other substances to avoid negative mood states (i.e., substance use coping) mediated the associations of sexual compulsivity and depressed mood with stimulant use. RESULTS: Younger age (adjusted OR [AOR]=0.58; 95% CI=0.47-0.70), HIV-positive serostatus (AOR=2.55; 95% CI=1.61-4.04), greater depressed mood (AOR=1.26; 95% CI=1.05-1.52) and higher sexual compulsivity (AOR=1.46; 95% CI=1.18-1.80) were independently associated with increased odds of stimulant use. Substance use coping partially mediated the associations of sexual compulsivity (beta(indirect)=0.11, p<.001) and depressed mood (beta(indirect)=0.13, p<.001) with stimulant use. CONCLUSIONS: Clinical research is needed to examine if interventions targeting sexual compulsivity and emotion regulation reduce stimulant use among MSM. PMID- 22088658 TI - Effect of essential inorganic metals on primary thermal degradation of lignocellulosic biomass. AB - This study employed thermogravimetric analysis (TGA) and analytical Py-GC/MS in order to examine the catalytic effect of main inorganic metals (K, Mg and Ca) on the thermal degradation and the formation of pyrolytic products in lignocellulosic biomass. In addition, potential mechanisms of the primary pyrolysis in presence of the inorganic metals were derived. TG analysis showed that when potassium content increased in the biomass, char formation increased from 10.5 wt.% to 19.6 wt.% at 550 degrees C, and temperatures at which the maximum degradation rate was achieved shifted from 367 degrees C to 333 degrees C. With increasing magnesium content, the maximum degradation rate increased from 1.21 wt.%/ degrees C to 1.43 wt.%/ degrees C. Analytical Py-GC/MS revealed that potassium had a distinguished catalytic effect promoting the formation of low molecular weight compounds and suppressing the formation of levoglucosan. An increase in the yield of C6 and C2C6 lignin derivatives with increasing potassium content was also observed. PMID- 22088659 TI - Safety of endovascular treatment of chronic cerebrospinal venous insufficiency: a report of 240 patients with multiple sclerosis. AB - PURPOSE: To evaluate the safety of outpatient endovascular treatment in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI). MATERIALS AND METHODS: A retrospective analysis was performed to assess complications occurring within 30 days of endovascular treatment of CCSVI. The study population comprised 240 patients; 257 procedures were performed over 8 months. The indication for treatment in all patients was symptomatic MS. Of the procedures, 49.0% (126 of 257) were performed in a hospital, and 51.0% (131 of 257) were performed in the office. Primary procedures accounted for 93.0% (239 of 257) of procedures, and repeat interventions accounted for 7% (18 of 257). For patients treated primarily, 87% (208 of 239) had angioplasty, and 11% (26 of 239) had stent placement; 5 patients were not treated. Of patients with restenosis, 50% (9 of 18) had angioplasty, and 50% (9 of 18) had stent placement. RESULTS: After the procedure, all but three patients were discharged within 3 hours. Headache after the procedure was reported in 8.2% (21 of 257) of patients; headache persisted > 30 days in 1 patient. Neck pain was reported in 15.6% (40 of 257); 52.5% (21 of 40) of these patients underwent stent placement. Three patients experienced venous thrombosis requiring retreatment within 30 days. Sustained intraprocedural arrhythmias were observed in three patients, and two required hospital admission. One of these patients, who was being retreated for stent thrombosis, was hospitalized because of a stress-induced cardiomyopathy. CONCLUSIONS: Endovascular treatment of CCSVI is a safe procedure; there is a 1.6% risk of major complications. Cardiac monitoring is essential to detect intraprocedural arrhythmias. Ultrasonography after the procedure is recommended to confirm venous patency and to identify patients experiencing acute venous thrombosis. PMID- 22088660 TI - In vitro pharmacodynamic evaluation of garenoxacin against quinolone-resistant Streptococcus pneumoniae. AB - The bactericidal activity and resistance selectivity of garenoxacin against Streptococcus pneumoniae with mutations in ParC (S79F) or both GyrA (S81F) and ParC (D83Y and K137N) were investigated using in vitro pharmacokinetic models simulating plasma concentrations for a standard clinical regimen [400mg once daily (q.d.)]. The efficacy of garenoxacin was compared with that of levofloxacin (500 mg q.d.) and moxifloxacin (400mg q.d.). Garenoxacin showed excellent bactericidal activity against S. pneumoniae, including quinolone-resistant S. pneumoniae (QRSP), achieving ratios of area under the plasma concentration-time curve over 24h to minimum inhibitory concentration (AUC(0-24)/MIC) >= 26.3, without emerging resistant subpopulations. The area above the killing curves was greater and the time to achieve 99.9% killing was shorter for garenoxacin than the corresponding values for levofloxacin and moxifloxacin. No resistant subpopulations and no additional substitution of amino acids in GyrA or ParC emerged following treatment with garenoxacin. On the other hand, in the parC mutant strain, levofloxacin and moxifloxacin treatment caused an increase in the frequency of the resistant population and an additional substitution of amino acids in GyrA (levofloxacin, S81Y/F/C; moxifloxacin, S81Y or E85K). In QRSP with mutations in GyrA and ParC, levofloxacin had no bactericidal activity, whilst the bactericidal activity of moxifloxacin was less than that of garenoxacin; moreover, an additional substitution of amino acids in ParC (S79Y) was noted. In conclusion, garenoxacin corresponding to an oral dose of 400mg showed excellent bactericidal activity against S. pneumoniae, including QRSP, without the emergence of resistant mutants. PMID- 22088661 TI - Clinically-oriented monitoring of acute effects of methylphenidate on cerebral hemodynamics in ADHD children using fNIRS. AB - OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD), a common developmental syndrome with inattention, hyperactivity, and impulsivity, is typically treated with the psychostimulant drug, methylphenidate (MPH). We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to search for a clinically implementable biological marker for the acute MPH effect on ADHD children. METHODS: Following an MPH washout period, twelve ADHD children performed a go/no-go task before and 1.5 h after MPH intake. fNIRS was used to monitor the lateral prefrontal cortical hemodynamics of ADHD children performing a go/no-go task. RESULTS: There was no significant activation in the lateral prefrontal cortices examined before MPH intake. However, after MPH intake, significant MPH-elicited activation (oxygenated hemoglobin signal increase) was detected in the right lateral prefrontal cortex (LPFC) implicated with response inhibition functions. There was a large significant correlation between increases in task performance and activation in the right LPFC. CONCLUSIONS: The improved cognitive performance was associated with activation in the right LPFC, which might serve as a biological marker to monitor the effect of MPH in ADHD children. SIGNIFICANCE: MPH-effect assessment in ADHD children using fNIRS can be performed within a 3 h stay at a hospital during a single visit, and thus may be integrated into clinical practice. PMID- 22088662 TI - A supplementary coil for 2H decoupling with commercial HCN MAS probes. AB - Partial deuteration is a powerful tool to increase coherence life times and spectral resolution in proton solid-state NMR. The J coupling to deuterium needs, however, to be decoupled to maintain the good resolution in the (usually indirect) (13)C dimension(s). We present a simple and reversible way to expand a commercial 1.3mm HCN MAS probe with a (2)H channel with sufficient field strength for J-decoupling of deuterium, namely 2-3kHz. The coil is placed at the outside of the stator and requires no significant modifications to the probe. The performance and the realizable gains in sensitivity and resolution are demonstrated using perdeuterated ubiquitin, with selectively CHD(2)-labeled methyl groups. PMID- 22088663 TI - Direct EPR irradiation of a sample using a quartz oscillator operating at 250 MHz for EPR measurements. AB - Direct irradiation of a sample using a quartz oscillator operating at 250 MHz was performed for EPR measurements. Because a quartz oscillator is a frequency fixed oscillator, the operating frequency of an EPR resonator (loop-gap type) was tuned to that of the quartz oscillator by using a single-turn coil with a varactor diode attached (frequency shift coil). Because the frequency shift coil was mobile, the distance between the EPR resonator and the coil could be changed. Coarse control of the resonant frequency was achieved by changing this distance mechanically, while fine frequency control was implemented by changing the capacitance of the varactor electrically. In this condition, EPR measurements of a phantom (comprised of agar with a nitroxide radical and physiological saline solution) were made. To compare the presented method with a conventional method, the EPR measurements were also done by using a synthesizer at the same EPR frequency. In the conventional method, the noise level increased at high irradiation power. Because such an increase in the noise was not observed in the presented method, high sensitivity was obtained at high irradiation power. PMID- 22088664 TI - [Far from the clinical trial... close to our reality]. PMID- 22088665 TI - [Diabetic male age 35 with spontaneous swelling of the left thigh]. PMID- 22088666 TI - [Reciprocal acknowledgement and decision-making shared with the patient]. AB - "Reciprocal recognition" is a philosophical concept that is essential to understand the attitudes that are basic for peaceful personal relationships. When it is not present, relationships in which people struggle for recognition are established. When the patients are excluded from the decision making regarding their health, their autonomy is not respected. This may make the patients feel like they are being treated as objects, with the consequent loss of trust in the doctor. An informed patient, that it, with their own criteria and desires to participate in what concerns them, is generating a group of growing tendencies. Reciprocal recognition applied to the physician-patient relationship need for one hand, the patient's trust in professional consulting and, secondly, the professional's initiative of sharing decisions with patients. The authors reflect on the concept of reciprocal recognition, with scenarios illustrating the consultation. PMID- 22088667 TI - [Morbi-mortality and use of recourses after acute coronary syndrome in a Spanish population]. AB - OBJECTIVES: To describe the management of patients suffering acute coronary syndrome (ACS) and to determine its clinical and economic consequences in a Spanish population. METHODS: A multicenter, retrospective claim database study including patient medical records from 6 primary care centers, two hospitals and two years of follow-up was carried out. Patients >=30 years, suffering a first acute coronary syndrome (ACS), between 2003 and 2007, were included. Groups: acute coronary syndrome with and without ST segment elevation. VARIABLES: socio demographic, co-morbidities, metabolic syndrome (MS), biochemical parameters, drugs, cumulative incidence (total mortality and cardiovascular events (CVE: including myocardial infarction, stroke and peripheral artery disease) and total costs. STATISTICAL ANALYSIS: logistic regression, Kaplan-Meier curves and ANCOVA; (P<.05). RESULTS: A total of 1020 patients were included. Mean age: 69 years; males: 65%. Groups: ST segment elevation ACS (N=632; 62%). Co-morbidities: hypertension (56%), dyslipidemia (46%) and diabetes (38%). Prevalence of MS: 59% (CI 95%: 56-62%). All biochemical parameters had improved after two years of follow-up. The average total cost per patient was ?14,069 (87% direct costs; 13% productivity loss costs). Direct costs: primary care (20%), specialty care (67%); hospitalization costs represented 63% of total costs. The average total cost for patients presenting more than one CVE was 22,750? vs 12,380? for those patients who suffered only one (P<.001). Cumulative incidence: total mortality 14%; CVE: 16%. CONCLUSIONS: In the current clinical practice, and despite the clinical efforts carried out, patients with an ACS are still at a high risk of suffering further CVE, representing a high cost burden to the health care system. PMID- 22088668 TI - [Acute coronary syndrome complicated by heart failure as predictor of long-term infarction]. AB - BACKGROUND: Heart failure (Killip>I) in patients with acute coronary syndrome (ACS) is a recognized risk factor for death. However, its relationship with the risk of new acute ischemic events has not been well established. OBJECTIVE: The aim of this study has been to evaluate the association between Killip>I on admission and the risk of a new acute myocardial infarction (AMI) during follow up due to ACS. PATIENTS AND METHODS: A total of 972 and 426 survivors of an ACS with non-ST segment evaluation (Non-STE-ACS) and AMI with ST segment elevation (STEMI) were studied prospectively and consecutively. The presence of Killip>I was determined on admission together with the classical prognostic variables. The relationship between Killip>I and subsequent post-discharge AMI was established with the Cox regression adapted for competitive events. RESULTS: During a median follow-up of 3 years, 135 (13.9%) and 53 (12.4%) patients with Non-STE-ACS and STEMI presented a new AMI. Patients with Non-STE-ACS and STEMI with Killip>I (15.6% and 21.3% respectively) showed a higher incidence of AMI (28.3 vs 6.3 and 10.6 vs 3.3 per 100 patients-years of follow-up, p<0.001, respectively). In the multivariate analysis, adjusted for traditional risk factors and controlled for competitive events (death and revascularization), confirmed that Killip>I subjects with Non-STE-ACS and STEMI showed a significantly higher risk of AMI (HR: 1.76; CI 95%: 1.15-2.68; p=0.009 and HR: 1.90; 95% CI: 1.07-3.36; p=0.029 respectively). CONCLUSIONS: In patients with Non-STE-ACS and STEMI, the presence of Killip>I on admission is independently associated to an increased risk of long term AMI. PMID- 22088669 TI - Multidimensional enantio gas chromtography/mass spectrometry and gas chromatography-combustion-isotopic ratio mass spectrometry for the authenticity assessment of lime essential oils (C. aurantifolia Swingle and C. latifolia Tanaka). AB - This article focuses on the genuineness assessment of Lime oils (Citrus aurantifolia Swingle and C. latifolia Tanaka), by Multi Dimensional Gas Chromatography (MDGC) to determine the enantiomeric distribution of alpha thujene, camphene, beta-pinene, sabinene, alpha-phellandrene, beta-phellandrene, limonene, linalool, terpinen-4-ol, alpha-terpineol and by gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) to determine the isotopic ratios of alpha-pinene, beta-pinene, limonene, alpha-terpineol, neral, geranial, beta-caryophyllene, trans-alpha-bergamotene, germacrene B. To the author's knowledge this is the first attempt to assess the authenticity and differentiate Persian Lime from Key lime oils by GC-C-IRMS. The results of the two analytical approaches were compared. The simultaneous use of the two techniques provides more reliable capability to detect adulteration in Citrus essential oils. In fact, in some circumstance only one of the two techniques allows to discriminate adulterated or contaminated oils. In cases where only small anomalies are detected by the two techniques due to subtle adulterations, their synergic use allows to express judgments. The advantage of both techniques is the low number of components the analyst must evaluate, reducing the complexity of the data necessary to deal with. Moreover, the conventional analytical approach based on the evaluation of the whole volatile fraction can fail to reveal the quality of the oils, if the adulteration is extremely subtle. PMID- 22088670 TI - The statistical overlap theory of chromatography using power law (fractal) statistics. AB - The chromatographic dimensionality was recently proposed as a measure of retention time spacing based on a power law (fractal) distribution. Using this model, a statistical overlap theory (SOT) for chromatographic peaks is developed that estimates the number of peak maxima as a function of the chromatographic dimension, saturation and scale. Power law models exhibit a threshold region whereby below a critical saturation value no loss of peak maxima due to peak fusion occurs as saturation increases. At moderate saturation, behavior is similar to the random (Poisson) peak model. At still higher saturation, the power law model shows loss of peaks nearly independent of the scale and dimension of the model. The physicochemical meaning of the power law scale parameter is discussed and shown to be equal to the Boltzmann-weighted free energy of transfer over the scale limits. The scale is discussed. Small scale range (small beta) is shown to generate more uniform chromatograms. Large scale range chromatograms (large beta) are shown to give occasional large excursions of retention times; this is a property of power laws where "wild" behavior is noted to occasionally occur. Both cases are shown to be useful depending on the chromatographic saturation. A scale-invariant model of the SOT shows very simple relationships between the fraction of peak maxima and the saturation, peak width and number of theoretical plates. These equations provide much insight into separations which follow power law statistics. PMID- 22088671 TI - Separation of imidacloprid and its degradation products using reversed phase liquid chromatography with water rich mobile phases. AB - Water rich mobile phases in RPLC are not generally used because of the longer retention times involved when organic modifiers such as methanol or acetonitrile are used. The problem of longer retention times can be addressed using hydrophobic alcohols such as pentanol in low quantities (less than 1%) as organic modifiers. The advantages of using these mobile phases in RPLC for the separation of water soluble and weakly retained congeners is demonstrated through the separation of imidacloprid and its degradation products using a 0.4% pentanol in water mobile phase with 0.2% acetic acid. PMID- 22088672 TI - Effects of the insulin sensitizing drug, pioglitazone, and lipopolysaccharide administration on markers of systemic inflammation and clinical parameters in horses. AB - Equine metabolic syndrome (EMS) is a condition of obese horses characterized by insulin resistance, systemic inflammation, and an increased risk of laminitis. The pathogenesis of EMS is thought, in part, to be due to inflammatory proteins produced by adipose tissue. Reducing inflammation may decrease the incidence of laminitis in horses with EMS. Pioglitazone hydrochloride, a thiazolidinedione, has efficacy to reduce obesity associated inflammation in humans. Eight normal, adult, horses were administered 1mg/kg pioglitazone for 14 days, and eight horses served as controls. Physical examination and hematologic variables, transcript abundance of pro-inflammatory cytokines in skeletal muscle and adipose tissue, and circulating concentrations of the acute phase protein, serum amyloid A and pro-inflammatory cytokine, TNF-alpha were assessed prior to, and following, an LPS infusion (35 ng/kg). The objective was to determine if pre-treatment with pioglitazone would mitigate the development of inflammation and associated clinical markers of inflammation following LPS administration. Lipopolysaccharide administration induced systemic inflammation, as assessed by clinical and hematological aberrations, increased TNF-alpha, SAA and adipose tissue IL-6 mRNA abundance, however no mitigating effects of pioglitazone were detected. A longer treatment period or higher dose might be indicated for future experiments. PMID- 22088673 TI - Immunogenicity of eight Mycobacterium avium subsp. paratuberculosis specific antigens in DNA vaccinated and Map infected mice. AB - Mycobacterium avium subsp. paratuberculosis (Map), the etiological agent of chronic enteritis of the small intestine in domestic and wild ruminants, causes substantial losses to livestock industry. Control of this disease is seriously hampered by the lack of adequate diagnostic tools and vaccines. Here we report on the immunogenicity of eight Map specific antigens, i.e. MAP1693c, Ag3, MAP2677c (identified by post-genomic and immunoproteomic analysis of Map secretome) and Ag5, Ag6, MAP1637c, MAP0388 and MAP3743 (identified by bioinformatic in silico screening of the Map genome). Strong, antigen-specific IFN-gamma responses were induced in mice vaccinated with plasmid DNA encoding MAP1693c, MAP1637c, MAP0388 and MAP3743. In contrast, T cell responses in Map infected mice were directed preferentially against Ag5 and to a lesser extent against MAP3743. None of the tested DNA vaccines conferred protection against subsequent challenge with Map. PMID- 22088674 TI - Development of a live, attenuated, potential vaccine strain of R. equi expressing vapA and the virR operon, and virulence assessment in the mouse. AB - Pneumonia caused by Rhodococcus equi remains a significant problem in foals. The objective of this study was to develop a safe and efficacious attenuated strain of R. equi for eventual use in oral immunization of foals. The approach involved expression of vapA in a live, virulence plasmid-negative, strain of R. equi (strain 103-). PCR-amplified fragments of the vapA gene, with and without the upstream genes virR, orf5, vapH, orf7 and orf8 (orf4-8), were cloned into a shuttle vector pNBV1. These plasmids, named pAW48A and pAWVapA respectively, were electroporated into strain 103-. The presence of the recombinant vectors in the attenuated strain (103-) and the integrity of the inserted genes were confirmed, and both constructs expressed VapA. The virulence of the two strains was compared to that of wild type R. equi 103+ and negative controls by their intravenous inoculation into mice, followed by examination of liver clearance 4 days later. Mice inoculated with R. equi 103-, 103-/pAWVapA and 103-/pNBV1 completely cleared infection, whereas strain 103-/pAW48A persisted in 47% of mice. PMID- 22088675 TI - Transcriptional analysis of equine lambda-light chains in the horse breeds Rhenish-German Coldblood and Hanoverian Warmblood. AB - The present study analyzed equine lambda-light chain genes (IGLV and IGLC) transcribed in the horse breeds Rhenish-German Coldblood (RGC) and Hanoverian Warmblood (HW). Primers were generated for the major expressed IGLV subgroup 8. The significant majority of the sequences represented IGLC6/7. In RGC, IGLC1 and IGLC5 were observed in significant higher frequencies than IGLC4. In HW, significant differences were obtained for the transcription of IGLC1 and IGLC5. IGLC4 was not determined in this breed. Five allotypic IGLC1 variants, four allotypic IGLC5 variants, and three allelic as well as two allotypic IGLC6/7 variants were identified. IGLC1(b, d), IGLC5(c, d), and IGLC6/7(a3, b) were detected in RGC while IGLC1(c) and IGLC5(b) were solely found in HW. Furthermore, 11 out of 144 known IGLV-segments were transcribed of which IGLV15 and IGLV17 were preferred significantly. IGLV25 displayed significant differences in the rearrangement between both breeds. The classified pseudogenes IGLV101psi and IGLV74psi were also identified. Rearrangements with IGLC-genes showed significant differences for IGLV15 in both breeds, whereas IGLV25 also revealed significant differences between the breeds. The transcriptional orientation of the functional segments has no influence on the occurrence of the IGLV. PMID- 22088676 TI - A rapid high-precision flow cytometry based technique for total white blood cell counting in chickens. AB - The automated analysis of total white blood cell count and white blood cell differentials is routine in research and clinical diagnosis in mammalian species. In contrast, in avian haematology these parameters are still estimated by conventional microscopic procedures due to technical difficulties associated with the morphological peculiarities of avian erythrocytes and thrombocytes. Both cell types are nucleated and fairly resistant to cell lysis, a prerequisite for automated leukocyte quantification and differentiation by commercial instruments. By using an anti-CD45 monoclonal antibody in combination with selected subset specific markers we have established a simple (no-lyse no-wash single-step one tube) flow cytometry based technique for high precision chicken blood cell quantification. EDTA-blood samples are diluted, spiked with fluorescence beads and incubated with a mixture of fluorochrome conjugated chicken leukocyte specific antibodies. We demonstrate that total leukocyte numbers as well as thrombocyte, monocyte, T-cell, B-cell and heterophilic granulocyte numbers can be determined by flow cytometry in a single step without prior cell lysis, cell separation or cell washing steps. Importantly, we also show that blood samples can be fixed prior to cell staining which enables shipping of samples making the technology widely available. Comparison of this technique with conventional microscopy revealed superior precision. By comparing leukocyte differentials of two chicken populations and during immune system development after hatch we demonstrate that large sample numbers can be analysed within hours. This technique will help to overcome previous restrictions in immune status analysis in chickens in experimental systems, during vaccine testing and health status monitoring in chicken flocks. Advances in avian genomics should facilitate the development of appropriate tools for other avian species in the future which will make this technique broadly applicable. PMID- 22088677 TI - Choosing homebirth--the women's perspective. AB - OBJECTIVE: To describe the decision-making process and birth experience of ten women in Finland who had planned to have a home birth. METHOD: The data were collected by means of in-depth interviews in 2008 and were analyzed using qualitative content analysis. RESULTS: Several reasons led to a decision to give birth at home. The main reasons were: previous birth experience, considering birth to be a natural process, increased autonomy, the home environment, intuition, the desire to choose the birth attendant, mistrust of the medical establishment and the opportunity to have the baby's siblings present at the birth. There were inhibiting and facilitating factors which influenced the women's decisions, and before making their decisions women sought out information about home birth. Home birth was an extremely positive experience and women highlighted their desire for the development of parent education to empower women in their preparations for birth. Full autonomy, the participation of family members, trust in one's ability to give birth and the absence of pharmacological pain relief were major contributors to the positive birth experience. The need for empowerment through parent education was highlighted in the interviews. CONCLUSION: To the women of this study home birth was very positive experience in which the autonomy was the important factor. According to this study maternity care services do not respond to women's individual wishes and services should be offer more alternatives and should be more empowering. PMID- 22088678 TI - Prediction of bone strength at the distal tibia by HR-pQCT and DXA. AB - BACKGROUND: Areal bone mineral density (aBMD) at the distal tibia, measured at the epiphysis (T-EPI) and diaphysis (T-DIA), is predictive for fracture risk. Structural bone parameters evaluated at the distal tibia by high resolution peripheral quantitative computed tomography (HR-pQCT) displayed differences between healthy and fracture patients. With its simple geometry, T-DIA may allow investigating the correlation between bone structural parameter and bone strength. METHODS: Anatomical tibiae were examined ex vivo by DXA (aBMD) and HR pQCT (volumetric BMD (vBMD) and bone microstructural parameters). Cortical thickness (CTh) and polar moment of inertia (pMOI) were derived from DXA measurements. Finally, an index combining material (BMD) and mechanical property (polar moment of inertia, pMOI) was defined and analyzed for correlation with torque at failure and stiffness values obtained by biomechanical testing. RESULTS: Areal BMD predicted the vBMD at T-EPI and T-DIA. A high correlation was found between aBMD and microstructural parameters at T-EPIas well as between aBMD and CTh at T-DIA. Finally, at T-DIA both indexes combining BMD and pMOI were strongly and comparably correlated with torque at failure and bone stiffness. CONCLUSION: Ex vivo, at the distal tibial diaphysis, a novel index combining BMD and pMOI, which can be calculated directly from a single DXA measurement, predicted bone strength and stiffness better than either parameter alone and with an order of magnitude comparable to that of HR-pQCT. Whether this index is suitable for better prediction of fracture risk in vivo deserves further investigation. PMID- 22088679 TI - The nature of memory failure in mild cognitive impairment: examining association with neurobiological markers and effect of progression. AB - The main goal of this study was to assess vulnerability to proactive interference and memory binding capacity, the ability to combine different information into a single coherent memory event, in persons with mild cognitive impairment (MCI). We also examined whether hippocampal atrophy and vascular burden were differentially related to these memory capacities in MCI. We further assessed whether memory performance and brain changes differ as a function of later development (or not) of dementia and whether they can predict progression to dementia. The study included 77 participants, 49 meeting the criteria for MCI and 28 healthy older adults. Results showed binding deficits and greater vulnerability to proactive interference in persons with MCI compared with healthy older adults. Hippocampal volume was associated with binding capacity, whereas vascular burden was associated with resistance to interference in persons with MCI. Follow-up analyses indicated that binding deficits predict progression from MCI to dementia. In conclusion, binding deficits and vulnerability to proactive interference are present in persons with MCI and are associated with different brain markers. However, only binding deficits predict progression to dementia. PMID- 22088682 TI - Almanac 2011: heart failure. The national society journals present selected research that has driven recent advances in clinical cardiology. PMID- 22088680 TI - Combined age- and trauma-related proteomic changes in rat neocortex: a basis for brain vulnerability. AB - This proteomic study investigates the widely observed clinical phenomenon, that after comparable brain injuries, geriatric patients fare worse and recover less cognitive and neurologic function than younger victims. Utilizing a rat traumatic brain injury model, sham surgery or a neocortical contusion was induced in 3 age groups. Geriatric (21 months) rats performed worse on behavioral measures than young adults (12-16 weeks) and juveniles (5-6 weeks). Motor coordination and certain cognitive deficits showed age-dependence both before and after injury. Brain proteins were analyzed using silver-stained two-dimensional electrophoresis gels. Spot volume changes (>2-fold change, p<0.01) were identified between age and injury groups using computer-assisted densitometry. Sequences were determined by mass spectrometry of tryptic peptides. The 19 spots identified represented 13 different genes that fell into 4 general age- and injury-dependent expression patterns. Fifteen isoforms changed differentially with respect to both age and injury (p<0.05). Further investigations into the nature and function of these isoforms may yield insights into the vulnerability of older patients and resilience of younger patients in recovery after brain injuries. PMID- 22088683 TI - Prediction of nitrobenzene toxicity to the algae (Scenedesmus obliguus) by quantitative structure-toxicity relationship (QSTR) models with quantum chemical descriptors. AB - In this study, Quantitative structure-toxicity relationship (QSTR) models were developed to predict the toxicity of nitrobenzene to the algae (Scenedesmus obliguus). Quantum chemical descriptors computed by PM3 Hamiltonian were used as predictor variables. The cross-validated Q2(cum) value for the optimal QSTR models is 0.867, indicating good predictive capability. The toxicity of nitrobenzenes (pC) was found to be affected by the molecular structure, the heat of formation (DeltaH(f)) and dipole moment (MU(z)). Contrary to the MU(z) values of nitrobenzenes, the DeltaH(f) values increase with increase in pC values and the energy of the highest occupied molecular orbital. Increasing the largest positive atomic charge on a nitrogen atom and the most positive net atomic charge on a hydrogen atom of the nitrobenzene leads to decrease in pC values. Nitrobenzenes with larger absolute hardness tend to be more stable and less toxic to the algae. PMID- 22088681 TI - Deriving prevalence estimates of depressive symptoms throughout middle and old age in those living in the community. AB - BACKGROUND: There is considerable debate about the prevalence of depression in old age. Epidemiological surveys and clinical studies indicate mixed evidence for the association between depression and increasing age. We examined the prevalence of probable depression in the middle aged to the oldest old in a project designed specifically to investigate the aging process. METHODS: Community-living participants were drawn from several Australian longitudinal studies of aging that contributed to the Dynamic Analyses to Optimise Ageing (DYNOPTA) project. Different depression scales from the contributing studies were harmonized to create a binary variable that reflected "probable depression" based on existing cut-points for each harmonized scale. Weighted prevalence was benchmarked to the Australian population which could be compared with findings from the 1997 and 2007 National Surveys of Mental Health and Well-Being (NSMHWB). RESULTS: In the DYNOPTA project, females were more likely to report probable depression. This was consistent across age levels. Both NSMHWB surveys and DYNOPTA did not report a decline in the likelihood of reporting probable depression for the oldest old in comparison with mid-life. CONCLUSIONS: Inconsistency in the reports of late-life depression prevalence in previous epidemiological studies may be explained by either the exclusion and/or limited sampling of the oldest old. DYNOPTA addresses these limitations and the results indicated no change in the likelihood of reporting depression with increasing age. Further research should extend these findings to examine within-person change in a longitudinal context and control for health covariates. PMID- 22088684 TI - Prescribing for children - taste and palatability affect adherence to antibiotics: a review. AB - The taste of an antibiotic is often not taken into account by practitioners, although there is significant evidence to show palatability correlates strongly with adherence. Many parents will be familiar with the difficulties of convincing young children to take bitter, unfamiliar medicine. Certain drugs, for example flucloxacillin, are so unpalatable that they should not be prescribed as syrups without prior 'taste testing' in an individual child, while others, such as oral cephalosporins, are accepted very well although they are more expensive with a broader antimicrobial spectrum than may be strictly necessary. Palatability is important in the broader context of global child health as regards the successful treatment of malaria, HIV and dehydration. The hidden cost of poor adherence resulting treatment failure, complications and the development of drug resistance cannot be over emphasised. Prescribing should involve parents, children and practitioners in an open discussion around the most suitable, palatable formulations for successful treatment outcomes. PMID- 22088685 TI - Re.: A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. PMID- 22088686 TI - Re.: Multi-institutional analysis of robotic partial nephrectomy for hilar versus nonhilar lesions in 446 consecutive cases. PMID- 22088687 TI - Re.: Natural history of renal cortical neoplasms during active surveillance with follow-up longer than 5 years. PMID- 22088688 TI - Re.: Recovery of renal function after open and laparoscopic partial nephrectomy. PMID- 22088689 TI - Re.: Raman spectroscopy: a novel experimental approach to evaluating renal tumours. PMID- 22088690 TI - Re.: Mechanisms of recurrence of Ta/T1 bladder cancer. PMID- 22088692 TI - Re.: Practice patterns and recurrence after partial cystectomy for bladder cancer. PMID- 22088694 TI - Re.: Impact of common medications on serum total prostate-specific antigen levels: analysis of the National Health and Nutrition Examination Survey. PMID- 22088695 TI - Re.: Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer: case-control study. PMID- 22088696 TI - Re.: Association between glomerular filtration rate, free, total, and percent free prostate-specific antigen. PMID- 22088697 TI - Re.: Suicide risk in men with prostate-specific antigen-detected early prostate cancer: a nationwide population-based cohort study from PCBaSe Sweden. PMID- 22088698 TI - Re.: Interval cancers in the Antwerp European Randomised Study of Screening for Prostate Cancer study, using a 6 year screening interval. PMID- 22088699 TI - Prostate cancer vs. post-biopsy hemorrhage: diagnosis with T2- and diffusion weighted imaging. PMID- 22088700 TI - Core 2 N-acetylglucosaminyltransferase-1 expression induces aggressive potential of testicular germ cell tumor. PMID- 22088701 TI - Re.: The effectiveness of the ultrasound bladder scanner in reducing urinary tract infections: a meta-analysis. PMID- 22088702 TI - Re.: Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. PMID- 22088703 TI - Re.: Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. PMID- 22088704 TI - Re.: Urological management of acute epididymo-orchitis in sexually active young men: too great a public health risk? PMID- 22088705 TI - Re.: Evidence for net renal tubule oxalate secretion in patients with calcium kidney stones. PMID- 22088706 TI - Re.: Clinical significance of uric acid dihydrate in urinary stones. PMID- 22088708 TI - Re.: Postmenopausal hormone use and the risk of nephrolithiasis: results from the Women's Health Initiative Hormone Therapy Trials. PMID- 22088709 TI - Re.: Nephrolithiasis-associated bone disease: pathogenesis and treatment options. PMID- 22088710 TI - Re.: Examination of the impact of airbags on renal injury using a national database. PMID- 22088711 TI - Re.: Pelvic fracture: the last 50 years. PMID- 22088712 TI - Re.: Assessment and management of an open bladder neck at posterior urethroplasty. PMID- 22088713 TI - Factors influencing the choice of urinary diversion in patients undergoing radical cystectomy. PMID- 22088714 TI - Re.: Transabdominal ultrasonography of detrusor wall thickness in women with overactive bladder. PMID- 22088715 TI - Re.: An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. PMID- 22088716 TI - Re.: The use of mesh in vaginal prolapse repair: do the benefits justify the risks? PMID- 22088718 TI - Re.: Pad per day usage, urinary incontinence and urinary tract infections in nursing home residents. PMID- 22088719 TI - Re.: Midurethral sling procedures for stress urinary incontinence in women over 80 years. PMID- 22088720 TI - Re.: The safety and efficacy of the "inside-out" trans-obturator Tvt in elderly versus younger stress-incontinent women: a prospective study of 353 consecutive patients. PMID- 22088722 TI - Re.: Association between lower urinary tract symptoms and vascular risk factors in aging men: the Hallym Aging Study. PMID- 22088721 TI - Re.: The effect of asymptomatic urethral caruncle on micturition in women with urinary incontinence. PMID- 22088723 TI - Korean urologist's view of practice patterns in diagnosis and management of benign prostatic hyperplasia: a nationwide survey. PMID- 22088724 TI - Incidence of histological prostatitis and its correlation with PSA density. PMID- 22088725 TI - A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. PMID- 22088726 TI - A study of renal outcomes in obese living kidney donors. PMID- 22088727 TI - Re: Low testosterone concentrations and the symptoms of testosterone deficiency according to the Androgen Deficiency in Ageing Males (ADAM) and Ageing Males' Symptoms Rating Scale (AMS) questionnaires. PMID- 22088728 TI - Re: The NERI hypogonadism screener: psychometric validation in male patients and controls. PMID- 22088729 TI - Re.: Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists. PMID- 22088730 TI - Re.: A prospective diary study of stuttering priapism in adolescents and young men with sickle cell anemia: report of an international randomized control trial; the Priapism in Sickle Cell Study (PISCES study). PMID- 22088731 TI - Re.: Overweight and seminal quality: a study of 794 patients. PMID- 22088734 TI - Re.: An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men. PMID- 22088735 TI - Re.: Soy protein isolates of varying isoflavone content do not adversely affect semen quality in healthy young men. PMID- 22088736 TI - Re.: Healthy overweight male partners of subfertile couples should not worry about their semen quality. PMID- 22088737 TI - Re.: Protamine contents and P1/P2 ratio in human spermatozoa from smokers and non smokers. PMID- 22088738 TI - Re.: Teaching children clean intermittent self-catheterization (CISC) in a group setting. PMID- 22088739 TI - Re.: Contemporary epidemiology and characterization of newborn males with prune belly syndrome. PMID- 22088740 TI - Re.: Evaluation of need for salvage continence procedures after failed modern staged repair. PMID- 22088741 TI - Re.: Failed exstrophy closure: management and outcome. PMID- 22088742 TI - Re.: Early life inorganic lead exposure induces testicular teratoma and renal and urinary bladder preneoplasia in adult metallothionein-knockout mice but not in wild type mice. PMID- 22088743 TI - Re.: A novel imaging approach for early detection of prostate cancer based on endogenous zinc sensing. PMID- 22088744 TI - Re.: Nonsteroidal selective androgen receptor modulators enhance female sexual motivation. PMID- 22088745 TI - Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation. PMID- 22088746 TI - Effects of Cl316,243, a Beta 3-adrenoceptor agonist, and intravesical prostaglandin E2 on the primary bladder afferent activity of the rat. PMID- 22088747 TI - Re.: Comparison of the thermal and histopathological effects of bipolar and monopolar electrosurgical resection of the prostate in a canine model. PMID- 22088748 TI - Re.: Relaxation effect of phosphodiesterase-5 inhibitor on the animal bladder and prostatic urethra: in vitro and in vivo study. PMID- 22088749 TI - Spontaneous echocardiographic contrast in an obstructed coronary sinus because of a perforated membrane. PMID- 22088750 TI - Complications of percutaneous mitral balloon valvotomy: usefulness of real-time 3 dimensional technology. PMID- 22088751 TI - "Surprise visitor". PMID- 22088752 TI - Thoracic epidural or paravertebral catheter for analgesia after lung resection: is the outcome different? AB - OBJECTIVE: The aim of this study was to determine whether thoracic epidural analgesia (TEA) or a paravertebral catheter block (PVB) with morphine patient controlled analgesia influenced outcome in patients undergoing thoracotomy for lung resection. DESIGN: A retrospective analysis. SETTING: A tertiary referral center. PARTICIPANTS: The study population consisted of 1,592 patients who had undergone thoracotomy for lung resection between May 2000 and April 2008. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Patients who received PVBs were younger, had a higher forced expiratory volume in 1 second, had a higher body mass index, a higher incidence of cardiac comorbidity, fewer pneumonectomies, and more wedge resections. A multivariable logistic regression model was used to develop a propensity-matched score for the probability of patients receiving an epidural or a paravertebral catheter. Four patients with an epidural to one with a paravertebral catheter were matched, with 488 patients and 122 patients, respectively. Postmatching analysis now showed no difference between the groups for preoperative characteristics or operative extent. Postmatching analysis showed no significant difference in outcome between the two groups for the incidence of postoperative respiratory complication (p = 0.67), intensive therapy unit (ITU) stay (p = 0.51), ITU readmission (p = 0.66), or in hospital mortality (p = 0.67). There was a significant reduction in the hospital length of stay in favor of the paravertebral group (6 v 7 days, p = 0.008). CONCLUSIONS: Paravertebral catheter analgesia with morphine patient-controlled analgesia seems as effective as thoracic epidural for reducing the risk of postoperative complications. The authors additionally found that paravertebral catheter use is associated with a shorter hospital stay and may be a better form of analgesia for fast-track thoracic surgery. PMID- 22088753 TI - Chromenones as potent bradykinin B1 antagonists. AB - A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chlorochromenone 15 was efficacious in a carrageenan-induced mechanical hyperalgesia model for chronic pain. PMID- 22088754 TI - Fluorescence behavior of non-functionalized carbon nanoparticles and their in vitro applications in imaging and cytotoxic analysis of cancer cells. AB - We report fluorescence behavior in non-functionalized carbon nanoparticles (NCNP) prepared from lamp soot and their application in imaging of normal and cancer cells. Structural characterization of these particles by Raman spectroscopy showed characteristic peaks located at 1350 and 1590 cm(-1) corresponding to the diamond-like (D) and graphite-like (G) bands of the carbon allotropes respectively with the characteristic ratio I(D)/I(G)=2.24. X-ray diffraction study confirmed the presence of amorphous as well as graphitized carbon in these nanostructures with minimum grain size ~2 nm. A typical luminescence lifetime measured by time resolved fluorescence spectroscopy was obtained 3.54 ns. The photoluminescence behavior of these particles was excitation dependent and gave off blue, green and red fluorescence under UV, blue and green excitation, respectively. Cellular uptake of these NCNP yielded excellent results for cell imaging of human embryonic kidney, lung carcinoma and breast adenocarcinoma cells. Cell imaging was further correlated with cytotoxicity in the above mentioned cell lines and also in leukemia cell lines. Dose dependant cytotoxicity was observed after 24 h up to 48 h of incubation of nanoparticles. Fluorescence microscopy of nanoparticle-cell interaction clearly indicated aggregation of the particles. PMID- 22088755 TI - Facile fabrication of biocompatible PLGA drug-carrying microspheres by O/W pickering emulsions. AB - This study is focused on the preparation of Ibuprofen (IBU) loaded micrometer sized poly(lactic-co-glycolic acid) (PLGA) microspheres and process variables on the size, drug loading and release during preparation of formulation. Silicon dioxide (SiO(2)) nanoparticle-coated PLGA microspheres were fabricated via a combined system of "Pickering-type" emulsion route and solvent volatilization method in the absence of any molecular surfactants. Stable oil-in-water emulsions were prepared using SiO(2) nanoparticles as a particulate emulsifier and a dichloromethane (CH(2)Cl(2)) solution of PLGA as an oil phase. The SiO(2) nanoparticle-coated PLGA microspheres were fabricated by the evaporation of CH(2)Cl(2) in situ, and then bare-PLGA microspheres were prepared by removal of the SiO(2) nanoparticles using HF aqueous solution. The two types of microspheres were characterized in terms of size, component and morphology using scanning electronic microscope (SEM), Fourier-transform infrared, optical microscope, and so on. Moreover, IBU was encapsulated into the hybrid beads by dispersing them in the CH(2)Cl(2) solution of PLGA in the fabrication process. The sustained release could be obtained due to the barrier of the polymeric matrix (PLGA). More over, the release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion. The combined system of Pickering emulsion and solvent volatilization opens up a new route to fabricate a variety of microspheres. The resulting microspheres may find applications as delivery vehicles for biomolecules, drugs, cosmetics and living cells. PMID- 22088756 TI - Poly (N-isopropylacrylamide)-PLA and PLA blend nanoparticles for temperature controllable drug release and intracellular uptake. AB - We designed a temperature-responsive and biodegradable novel drug-delivery carrier. A block copolymer, poly (N-isopropylacrylamide-dl-lactide) (PNIPAAm PLA), was synthesized by the ring-opening polymerization of dl-lactide, and used as a carrier for a drug-delivery system. In this study, temperature-responsive nanoparticles (NPs) encapsulating betamethasone disodium 21-phosphate (BP) were prepared from a blend of PLA homopolymer and block copolymers by an oil-in-water solvent-diffusion method in the presence of zinc ion (PLA/PNIPAAm-PLA (NPs)). The resulting NP size was around 140 nm. The drug release from temperature-responsive NP could be controllable by changing the temperature. Moreover, a murine macrophage-like cell line, RAW 264.7 cells, was used to measure and image the cell uptake of fluorescent PLA/PNIPAAm-PLA NPs at 30 degrees C and 37 degrees C on the boundary of LCST (34 degrees C). Below the LCST, cellular uptake was not observed, but contrary to cellular uptake it was clearly observed above the LCST. Moreover, we found this effect to be useful for controlling the stealthiness by changing the temperature. Present temperature-responsive NPs have successfully exhibited thermo-responsive drug release and intracellular uptake while possessing a biodegradable character. PMID- 22088757 TI - Thermo-responsive poly(N-isopropylacrylamide) grafted onto microtextured poly(dimethylsiloxane) for aligned cell sheet engineering. AB - Poly(N-isopropylacrylamide) (PNIPAAm)-grafted poly(dimethylsiloxane) (PDMS) offers an inexpensive, biocompatible, oxygen permeable, and easily microtextured thermo-responsive substrate for producing cell sheets. This study introduces a method of grafting PNIPAAm onto microtextured PDMS that is suitable for generating aligned vascular smooth muscle cell (VSMC) sheets. We examined a wide range of processing parameters in order to identify the conditions that led to acceptable sheet growth and detachment behavior. Substrates grafted under these conditions produced confluent cell sheets that fully detached in less than 10 min after lowering the culture temperature from 37 degrees C to 20 degrees C. The grafted layer thickness was determined to be 496+/-8 nm by atomic force microscopy. Surface characterization by Fourier transform infrared spectroscopy showed a relative grafting yield of 0.488+/-0.10, defined as the ratio of the PNIPAAm 1647 cm(-1) to the PDMS 2962 cm(-1) absorbance peaks. The water contact angle of the substrates was shown to change from 89.6 degrees to 101.0 degrees at 20 degrees C and 37 degrees C, respectively. We also found that cell behavior on PNIPAAm-grafted PDMS was not directly related to surface wettability or relative grafting densities. PMID- 22088758 TI - Enhanced tissue penetration-induced high bonding strength of a novel tissue adhesive composed of cholesteryl group-modified gelatin and disuccinimidyl tartarate. AB - The aim of this study was to evaluate the effect of cholesteryl group content on the bonding strength of a novel tissue adhesive composed of cholesteryl group modified geletin (CholGltn) and disuccinimidyl tartarate (DST). The bonding strength of this tissue adhesive with fresh arterial media reached a maximum at a CholGltn content of 70% in the CholGltn/gelatin (Gltn) mixture, which then decreased with increasing CholGltn content with a fixed succinimidyl group:amino group ratio of 1:1. The maximum bonding strength obtained was 6-fold higher compared with that of the original Gltn. Furthermore, maximum peeling strength was also obtained at a CholGltn content of 70% in the CholGltn/Gltn mixture and at a similar succinimidyl group:amino group ratio. The highest peeling strength was 8-fold higher compared with Gltn and 6-fold higher compared with commercial aldehyde-based adhesive. After exposure of FITC-labeled Gltn or CholGltn to aortic smooth muscle cells (SMCs), which are abundant in arterial media, CholGltn integrated effectively with the surface of SMCs. This indicated that FITC-labeled CholGltn anchors into the cell membrane of SMCs. From these results, it was demonstrated that tissue adhesive composed of a CholGltn/Gltn mixture and DST showed improved penetration into arterial media compared with adhesive composed of Gltn and DST. This behavior supports the suggestion that the hydrophobic cholesteryl group in Gltn contributes to the enhanced bonding/peeling strength. This novel tissue adhesive may become a useful material in the clinical field for the treatment of aortic dissection. PMID- 22088759 TI - Single-walled carbon nanotubes-polymer modified graphite electrodes for DNA hybridization. AB - Single-walled carbon nanotubes (SWCNT)-poly(vinylferrocenium) (PVF(+)) modified pencil graphite electrodes (PGEs) were developed in our study for the electrochemical monitoring of a sequence-selective DNA hybridization event. Firstly, SWCNT-PVF(+) modified PGE, PVF(+) modified PGE and unmodified PGE were characterized using scanning electron microscopy (SEM). The electrochemical behavior of these electrodes was then investigated using electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The SWCNT PVF(+) modified PGEs were optimized for improved DNA sensing ability by measuring the guanine oxidation signal. In order to obtain the full coverage immobilization of the DNA probe following the optimum working conditions, the effect of amino linked, thiol-linked and, bare oligonucleotides (ODNs), and the concentration of the DNA probe on the response of the modified electrode were examined. After optimization studies, the sequence-selective DNA hybridization was evaluated in the case of hybridization between an amino-linked probe and its complementary (target), a noncomplementary (NC) sequence, calf thymus double stranded DNA (dsDNA), and target/mismatch (MM) mixtures in the ratio of 1:1. SWCNT-PVF(+) modified PGEs presented very effective discrimination of DNA hybridization owing to their superior selectivity and sensitivity. PMID- 22088760 TI - A double-targeted magnetic nanocarrier with potential application in hydrophobic drug delivery. AB - A double-targeted magnetic nanocarrier based with potential applications in the delivery of hydrophobic drugs has been developed. It consists of magnetite (Fe(3)O(4)) nanoparticles encapsulated in self-assembled micelles of the amphiphilic copolymer MPEG-PLGA [methoxy poly (ethylene glycol)-poly (d,l-lactide co-glycolide)], and was fabricated using the solvent-evaporation technique. The magnetic nanocarrier has a very stable core-shell structure and is superparamagnetic. Its cytotoxicity was evaluated using the MTT assay with three cell lines-HeLa, MCF-7, and HT1080; it exhibited no cytotoxicity against any tested line at concentrations of up to 400 MUg/mL after incubation for 24 h. Its cellular uptake was studied by Prussian blue staining and by fluorescence microscopy after encapsulating a fluorescent probe (hydrophobic quantum dots) into the nanocarrier. Finally, the magnetic targeting property of the magnetic nanocarrier was confirmed by an in vitro test. Overall, the results obtained demonstrate the potential of the double-targeted nanocarrier for the intracellular delivery of hydrophobic drugs. PMID- 22088761 TI - Development and validation of an HPLC-based screening method to acquire polyhydroxyalkanoate synthase mutants with altered substrate specificity. AB - A rapid and convenient method for the compositional analysis of polyhydroxyalkanoate (PHA) was developed using high-performance liquid chromatography (HPLC) and alkaline sample pretreatment in a 96-well plate format. The reliability of this system was confirmed by the fact that a mutant with a D171G mutation of Aeromonas caviae PHA synthase (PhaC(Ac)), which gained higher reactivity toward 3-hydroxyhexanoate (3HHx), was selected from the D171X mutant library. Together with D171G mutant, several single mutants showing high reactivity toward 3HHx were isolated by the HPLC assay. These new mutants and double mutants combined with an N149S mutation were used to synthesize P(3 hydroxybutyrate-co-3HHx) in Ralstonia eutropha PHB(-)4 from soybean oil as carbon source, achieving higher levels of 3HHx fraction than the wild-type enzyme. Based on these results, the high-throughput screening system will serve as a powerful tool for exploring new and beneficial mutations responsible for regulating copolymer composition of PHA. PMID- 22088762 TI - A dynamical approach to contact distance based protein structure determination. AB - Protein native structure topology based folding dynamics captures many aspects of protein folding. The fact that folding is driven by a potential derived only from residue pairs in native contact, a sparse distance matrix, lead us to postulate this as a solution method to the molecular distance geometry problem. In the standard Go model non-bonded residues move under the influence of a Lennard-Jones potential and consequently folding is slow. In this study we apply a faster quadratic potential Go model to solving the full-atom distance geometry problem, where distance data is based only on residue atoms within 5 A in the native structure. We show that the method works well when only atomic contact data is known and when a substantial proportion of this contact data is missing. Also, we show that the method can be applied in conjunction with secondary structure prediction schemes to enhance accuracy in cases of missing contact data. PMID- 22088763 TI - Enrichment of virtual hits by progressive shape-matching and docking. AB - The main applications of virtual chemical screening include the selection of a minimal receptor-relevant subset of a chemical library with a maximal chemical diversity. We have previously reported that the combination of ligand-centric and receptor-centric virtual screening methods may provide a compromise between computational time and accuracy during the hit enrichment process. In the present work, we propose a "progressive distributed docking" method that improves the virtual screening process using an iterative combination of shape-matching and docking steps. Known ligands with low docking scores were used as initial 3D templates for the shape comparisons with the chemical library. Next, new compounds with good template shape matches and low receptor docking scores were selected for the next round of shape searching and docking. The present iterative virtual screening process was tested for enriching peroxisome proliferator activated receptor and phosphoinositide 3-kinase relevant compounds from a selected subset of the chemical libraries. It was demonstrated that the iterative combination improved the lead-hopping practice by improving the chemical diversity in the selected list of virtual hits. PMID- 22088764 TI - Adsorption of Pb(II) and Cu(II) from aqueous solution on magnetic porous ferrospinel MnFe2O4. AB - The adsorption of Pb(II) and Cu(II) from aqueous solution on magnetic porous ferrospinel MnFe(2)O(4) prepared by a sol-gel process was investigated. Single batch experiment was employed to test pH effect, sorption kinetics, and isotherm. The interaction mechanism and the regeneration were also explored. The results showed that Pb(II) and Cu(II) removal was strongly pH-dependent with an optimum pH value of 6.0, and the equilibrium time was 3.0 h. The adsorption process could be described by a pseudo-second-order model, and the initial sorption rates were 526.3 and 2631.5 MUmol g(-1)min(-1) for Pb(II) and Cu(II) ions, respectively. The equilibrium data were corresponded well with Langmuir isotherm, and the maximum adsorption capacities were 333.3 and 952.4 MUmol g(-1) for Pb(II) and Cu(II) ions, respectively. The adsorbed Pb(II) and Cu(II) ions were in the form of the complex with oxygen in carboxyl and hydroxyl groups binding on the surface of magnetic porous MnFe(2)O(4). The sorbent could be reused for five times with high removal efficiency. PMID- 22088765 TI - Viscosity contribution of an arbitrary shape rigid aggregate to a dilute suspension. AB - The study of rheological response of solid suspensions is essential in understanding the relationships governing their kinematics and dynamics. However the study is complicated mainly by the complex interplay between suspension rheology and hydrodynamic behavior of the suspended solids, which for most of the practically occurring situations have complex and arbitrary shapes, and exact equations accounting for their hydrodynamic contribution are not available. For this reason, using a recently developed methodology capable of computing the average rigid body resistance matrix of arbitrary shaped clusters made of uniform sized spheres, Brownian dynamic simulations under shear conditions are performed for clusters with different geometries with the objective of estimating their intrinsic viscosity. The population of clusters chosen encompassed a broad range of morphologies, such as fractals with a wide range of masses and fractal dimension values, dense clusters with spherical and spheroidal aspect ratios, similar to those produced during coagulation experiments of colloidal suspensions. It was found that fractal clusters with low fractal dimensions and spheroidal clusters have sufficient structural anisotropies to show deviations from Einstein's relationship, and display a moderate shear thinning behavior, as well as a non-negligible linear viscoelasticity. On the other hand, clusters with high fractal dimensions tend to behave progressively more like spheres as their fractal dimension increases. We also found that the intrinsic viscosity of all clusters, independent of their morphology, can be quantitatively predicted by means of an equivalent ellipsoid model, in which clusters are modeled as ellipsoids with the same principal moments of inertia. PMID- 22088766 TI - Shape-directing role of cetyltrimethylammonium bromide in the preparation of silver nanoparticles. AB - We report a simple chemical reduction method for the synthesis of different colored silver nanoparticles, AgNP, using tyrosine as a reducing agent. Effects of cetyltrimethylammonium bromide, CTAB, and tyrosine concentrations are analyzed by UV-visible measurements and scanning electron microscopy (SEM) to evaluate the mode of AgNP aggregation. The position and shape of the surface resonance plasmon absorption bands strongly depend on the reaction conditions, i.e., [CTAB], [tyrosine], and reaction time. Sub-, post-, and dilution-micellar effects are accountable for the fast and slow nucleation and growth processes. Spectrophotometric measurement also shows that the average size and the polydispersity of AgNP increase with [CTAB] in the solution. CTAB acted as a shape-directing agent. PMID- 22088767 TI - Cholesteryl ester transfer protein inhibition to reduce cardiovascular risk: Where are we now? AB - Elevated low-density lipoprotein-cholesterol (LDL-C) and reduced high-density lipoprotein-cholesterol (HDL-C) are major risk factors for the development of cardiovascular disease. One approach to raising HDL-C is to inhibit the cholesteryl ester transfer protein (CETP), a plasma protein that promotes transfer of cholesteryl esters from HDL and other lipoprotein fractions. Drugs that inhibit CETP increase HDL-C and some lower LDL-C. However, the development of torcetrapib, the first CETP inhibitor to be tested in a human clinical outcomes trial, was terminated because it caused an excess of deaths and cardiovascular events. There is evidence, however, that torcetrapib had adverse off-target effects unrelated to CETP inhibition. This has opened the way for retesting of the hypothesis that CETP inhibitors will be anti-atherogenic in studies conducted with agents such as dalcetrapib and anacetrapib that do not share the off-target effects of torcetrapib. Clinical outcome trials with dalcetrapib and anacetrapib are currently under way. PMID- 22088768 TI - Using a legal and regulatory framework to identify and evaluate priorities for cancer prevention. AB - This paper presents a framework for identifying legal and regulatory interventions for the prevention of risk factors for cancer at the population level. The framework has wider application for behavioural risk factors for other non-communicable diseases. It is based on four different types of assessment: identifying the determinants of cancer and key settings for interventions; reviewing the key strategies that law can deploy; considering the most appropriate level for interventions within federal systems; and considering the role of law within a broader set of public health responses that includes voluntary standards, co-regulation, outcome-based regulation and more technical, prescriptive controls. The paper argues that law is an important tool for preventing the burden of disease from cancer. It then uses the framework to evaluate the current status of regulatory strategies for cancer prevention and to identify law reform priorities, taking Australia as a case study. The paper illustrates the application of the model at the country level by making extensive use of Australian evidence and published research. However, the methodology presented, the regulatory issues discussed, the evidence cited and the law reform priorities identified will be relevant to other countries with a substantial burden from cancer and non-communicable diseases. PMID- 22088769 TI - Can law improve prevention and treatment of cancer? PMID- 22088770 TI - Abuse experiences, substance use, and reproductive health in women seeking care at an emergency department. AB - INTRODUCTION: Abuse experiences can have negative health consequences for women. Many women present to the emergency department for episodic, nonemergent care and may have unique needs as survivors of abuse. The purpose of this study was to describe child sexual abuse experiences, intimate partner violence, substance use, and reproductive health outcomes in a sample of adult women who were seeking care from a rural emergency department to better understand the health care needs of this unique population. METHODS: One hundred forty-five adult women (18-45 years old) were recruited at an emergency department in the southeastern United States. Questionnaires were used to assess for demographic characteristics, history of child sexual abuse (CSA), intimate partner violence, reproductive health, and substance use. RESULTS: In the sample, 42.8% of women (n = 62) reported a positive history of CSA and 34.7% of women (n = 49) experienced intimate partner physical violence during the past year. More than 46% of the women (n = 65) had harmful drinking patterns in the past year and more than 50% reported some type of substance use in the past 3 months. Women who experienced CSA had a significantly greater number of lifetime sexual partners, were more likely to report pain with sexual intercourse, and were more likely to report a medical history of an abnormal Papanicolaou smear. DISCUSSION: The women in this sample had high rates of abuse, harmful drinking patterns, and substance use and were at risk for sexually transmitted infections. Through screening for lifetime violence, including sexual violence, emergency nurses can be an important liaison between women who have experienced CSA and appropriate referrals within the health care system. PMID- 22088771 TI - Screening, brief intervention, and referral to treatment: a nursing perspective. PMID- 22088772 TI - Being prepared for the unprepared: a phenomenology field study of Swedish prehospital care. AB - INTRODUCTION: This paper presents a study of prehospital care with particular focus on how ambulance personnel prepare themselves for their everyday assignments. METHODS: The caring science field study took a phenomenological approach, where data were analyzed for meaning. Two specialist ambulance nurses, three registered nurses, and six paramedics participated. RESULTS: The previously known discrepancy between in-hospital care and prehospital care was further interpreted in this study. The pre-information from an emergency medical dispatch (EMD) center provides ambulance personnel with basic expectations as to what they will have to take care of. At the same time that they maintain their certainty and control, our major findings indicate that prehospital care in emergency medical service requires the personnel to be prepared for an open and flexible encounter with the patient; to be prepared for the unprepared, i.e., to be open and to avoid being governed by predetermined statements. DISCUSSION: Our findings suggest that the outcomes of good prehospital care affect patient security. The seemingly time-consuming dialogue with the patient facilitates understanding and decision-making regarding the patient's medical needs, and it is comforting to the patient. The ambulance personnel need to be well prepared for this task and fully understand that the situation might differ considerably from the information provided by the EMD centers. All objective information is of great value in this care context, but ultimately it is the patient who provides reliable information about her/his own situation. PMID- 22088773 TI - Match probabilities for multiple siblings. AB - A defendant whose DNA profile matches that of a crime stain may argue that he has several, say n, brothers and that one of them may have been the origin of the crime stain. If the probability for any of the brothers considered separately to match the crime stain profile is p, we show that the probability that at least one of the n brothers match is strictly smaller than np. This latter quantity therefore is an easy to compute and conservative value to report. PMID- 22088774 TI - [Spirometry as method of screening and intervention in high- risk smokers in primary care]. AB - OBJECTIVE: To show the effectiveness of screening in the detection of new cases of COPD in smokers of high-risk, and to describe the characteristics associated with COPD, as well as determine the predisposition to quit. DESIGN: A cross sectional and multicentre study. LOCATION: Basic Primary Care Centres representing different rural and urban areas of Lleida. PARTICIPANTS: A total of 497 active smokers without COPD from 40 to 70 years selected from the database Primary Care Database (e-CAP). INTERVENTION: Spirometry was performed on all patients. The spirometry results were reported and brief counselling was given on quitting smoking and the readiness to stop smoking was determined. VARIABLES: Age, gender, height, weight, smoking, respiratory symptoms and physical activity. RESULTS: The majority of patients (65.4%) were men, age 51+/- 7.6 years. They smoked an average of 32 packs/year; 40.4% performed moderate activity and 27.4% referred to some respiratory symptoms. Of the 25% who had an obstructive or mixed pattern, 75.8% of the cases had a moderate level of severity. A decision to quit was made by 38.8%. In the multivariate analysis, gender, age 50 to 59 years and a smoking index>40 were associated with COPD. Moderate or intense physical activity decreased the risk of COPD. CONCLUSIONS: To perform spirometry in high-risk smokers, to show the spirometry results and give brief anti-smoking counselling, enables not previously diagnosed cases of COPD to be detected. It also helps to determine the readiness to stop smoking and to establish individualised treatment and follow-up plans. PMID- 22088775 TI - Mighty metaphors: behavioral and ERP evidence that power shifts attention on a vertical dimension. AB - Thinking about the abstract concept power may automatically activate the spatial up-down image schema (powerful up; powerless down) and consequently direct spatial attention to the image schema-congruent location. Participants indicated whether a word represented a powerful or powerless person (e.g. 'king' or 'servant'). Following each decision, they identified a target at the top or bottom of the visual field. In Experiment 1 participants identified the target faster when their spatial position was congruent with the perceived power of the preceding word than when it was incongruent. In Experiment 2 ERPs showed a higher N1 amplitude for congruent spatial positions. These results support the view that attention is driven to the image schema congruent location of a power word. Thus, power is partially understood in terms of vertical space, which demonstrates that abstract concepts are grounded in sensory-motor processing. PMID- 22088776 TI - A key role for experimental task performance: effects of math talent, gender and performance on the neural correlates of mental rotation. AB - The neurophysiological mechanisms underlying superior cognitive performance are a research area of high interest. The majority of studies on the brain-performance relationship assessed the effects of capability-related group factors (e.g. talent, gender) on task-related brain activations while only few studies examined the effect of the inherent experimental task performance factor. In this functional MRI study, we combined both approaches and simultaneously assessed the effects of three relatively independent factors on the neurofunctional correlates of mental rotation in same-aged adolescents: math talent (gifted/controls: 17/17), gender (male/female: 16/18) and experimental task performance (median split on accuracy; high/low: 17/17). Better experimental task performance of mathematically gifted vs. control subjects and male vs. female subjects validated the selected paradigm. Activation of the inferior parietal lobule (IPL) was identified as a common effect of mathematical giftedness, gender and experimental task performance. However, multiple linear regression analyses (stepwise) indicated experimental task performance as the only predictor of parietal activations. In conclusion, increased activation of the IPL represents a positive neural correlate of mental rotation performance, irrespective of but consistent with the obtained neurocognitive and behavioral effects of math talent and gender. As experimental performance may strongly affect task-related activations this factor needs to be considered in capability-related group comparison studies on the brain-performance relationship. PMID- 22088777 TI - Are imaging and lesioning convergent methods for assessing functional specialisation?: investigations using an artificial neural network. AB - This article presents an investigation of the relationship between lesioning and neuroimaging methods of assessing functional specialisation, using synthetic brain imaging (SBI) and lesioning of a connectionist network of past-tense formation. The model comprised two processing 'routes': one was a direct route between layers of input and output units, while the other, indirect, route featured an intermediate layer of processing units. Emergent specialisation within the network was assessed (1) by lesioning either the direct or indirect route and measuring past-tense performance for regular and irregular verbs, and (2) by measuring functional activation in each route when processing each verb type (SBI). SBI and lesioning approaches failed to converge when network activation was summed over each route in our SBI approach. Examination of individual network solutions suggested that the verb types might be using the indirect route differently in terms of the pattern of activation across the route, rather than in terms of gross activation. A subsequent SBI analysis compared patterns of activation in the indirect route and confirmed that these patterns were more similar between regular-type verbs than between regular and irregular verbs. As the spatial and temporal resolution of neuroimaging techniques improves, the results of this investigation suggest that the key to finding functional specialisation will be to distinguish local coding differences across behaviours that are the results of developmental processes. Other analyses suggest that lesioning data may be limited because, with increasing damage, they reveal the resting activations of a computational system rather than a computational specialisation per se. PMID- 22088778 TI - An integrated account of generalization across objects and features. AB - Humans routinely make inductive generalizations about unobserved features of objects. Previous accounts of inductive reasoning often focus on inferences about a single object or feature: accounts of causal reasoning often focus on a single object with one or more unobserved features, and accounts of property induction often focus on a single feature that is unobserved for one or more objects. We explore problems where people must make inferences about multiple objects and features, and propose that people solve these problems by integrating knowledge about features with knowledge about objects. We evaluate three computational methods for integrating multiple systems of knowledge: the output combination approach combines the outputs produced by these systems, the distribution combination approach combines the probability distributions captured by these systems, and the structure combination approach combines a graph structure over features with a graph structure over objects. Three experiments explore problems where participants make inferences that draw on causal relationships between features and taxonomic relationships between animals, and we find that the structure combination approach provides the best account of our data. PMID- 22088779 TI - Does the Framingham Stroke Risk Profile predict white-matter changes in late-life depression? AB - BACKGROUND: Cardiovascular risk factors and diseases are important etiological factors in depression, particularly late-life depression. Brain changes associated with vascular disease and depression can be detected using magnetic resonance imaging. Using diffusion tensor imaging (DTI), we investigated whether the Framingham Stroke Risk Profile (FSRP), a well-validated risk prediction algorithm, is associated with changes in white-matter connectivity. We hypothesized that depressed participants would show reduced white-matter integrity with higher FSRP, and non-depressed controls (matched for mean vascular risk) would show minimal co-variance with white-matter changes. METHODS: Thirty six participants with major depression (age 71.8 +/- 7.7 years, mean FSRP 10.3 +/ 7.6) and 25 controls (age 71.8 +/- 7.3 years, mean FSRP 10.1 +/- 7.7) were clinically interviewed and examined, followed by 60-direction DTI on a 3.0 Tesla scanner. Image analysis was performed using FSL tools (www.fmrib.ox.ac.uk/fsl) to assess the correlation between FSRP and fractional anisotropy (FA). Voxelwise statistical analysis of the FA data was carried out using Tract Based Spatial Statistics. The significance threshold for correlations was set at p < 0.05 using threshold-free cluster-enhancement. Partial correlation analysis investigated significant correlations in each group. RESULTS: Participants in the depressed group showed highly significant correlations between FSRP and FA within the body of corpus callosum (r = -0.520, p = 0.002), genu of corpus callosum (r = -0.468, p = 0.005), splenium of corpus callosum (r = -0.536, p = 0.001), and cortico spinal tract (r = -0.473, p = 0.005). In controls, there was only one significant correlation in the body of corpus callosum (r = -0.473, p = 0.023). CONCLUSIONS: FSRP is associated with impairment in white-matter integrity in participants with depression; these results suggest support for the vascular depression hypothesis. PMID- 22088780 TI - Prosthetic knee infection in the young immigrant patient--do not forget tuberculosis! AB - Skeletal tuberculosis (TB) frequently masquerades as more common etiologies and can be difficult to diagnose. We describe a case of TB knee arthritis in a young Haitian-born woman in whom the diagnosis was not initially suspected, resulting in treatment with total knee arthroplasty that subsequently failed. A long course of medical and surgical therapies was then necessary to treat this patient. Issues in the diagnosis and management of TB in the native and prosthetic knee joint are presented. PMID- 22088781 TI - Predictors of intensive care unit admission after total joint arthroplasty. AB - Total joint arthroplasty (TJA) is a relatively safe orthopedic procedure. However, complications do occur, and some may necessitate admission to the intensive care unit (ICU). Our purpose was to determine risk factors associated with admittance to ICU after TJA. We evaluated 22,343 primary and revision total hip and knee arthroplasties from 1999 to 2008. One hundred thirty patients were admitted to the ICU. Cases were matched 1:2 for date of surgery, surgeon, and type of surgery. The causes for admission to ICU were recorded. Independent risk factors for ICU admission were smoking, cemented arthroplasty, general anesthesia, allogenic transfusion, higher C-reactive protein, lower hemoglobin level, higher body mass index, and older age. Proper identification and management of these "at-risk" patients may decrease the incidence of ICU admittance after TJA. PMID- 22088782 TI - Accuracy of dynamic tactile-guided unicompartmental knee arthroplasty. AB - Unicompartmental knee arthroplasty (UKA) can achieve excellent clinical and functional results for patients having single-compartment osteoarthritis. However, UKA is considered to be technically challenging to perform, and malalignment of implant components significantly contributes to UKA failures. It has been shown that surgical navigation and tactile robotics could be used to provide very accurate component placement when the bones were rigidly fixed in a stereotactic frame during preparation. The purpose of this investigation was to determine the clinically realized accuracy of UKA component placement using surgical navigation and tactile robotics when the bones are free to move. A group of 20 knees receiving medial UKA with dynamically referenced tactile-robotic assistance was studied. Implant placement errors were comparable with those achieved using tactile robotics with rigid stereotactic fixation. PMID- 22088783 TI - Incidence of clinically significant venous thromboembolic events in Asian patients undergoing total knee arthroplasty without anticoagulation. AB - This study aimed to evaluate the incidence of clinically significant venous thromboembolic events (VTE) in Asian patients undergoing total knee arthroplasty (TKA) without anticoagulation. All patients who underwent TKA by a single surgeon from 2006 to 2010 in Singapore General Hospital were reviewed. Only symptomatic patients were referred for ultrasonography. Of the 531 patients reviewed, 3 patients developed symptoms of deep vein thrombosis with subsequent ultrasonographic confirmation, whereas 1 patient developed fatal pulmonary embolism without any clinical or radiologic evidence of deep vein thrombosis. Hence, the incidence of clinically significant VTE was 0.75%. Given the low incidence of clinically significant VTE, there is a need to review the current practice of routine chemoprophylaxis in Asian patients undergoing TKA. PMID- 22088784 TI - Cerebral and mesenteric tissue oxygenation by positional changes in very low birth weight premature infants. AB - AIM: There has been no clear consensus of the appropriate positioning in preterm infants. We aimed to evaluate the changes of cerebral and mesenteric tissue oxygenation in three different positions, by near infrared spectroscopy (NIRS), in stable very low birth weight (VLBW) infants of postnatal >30 days. METHODS: NIRS monitoring of cerebral and mesenteric tissue oxygenation in three different positions was performed in 29 stable preterm newborns in neonatal intensive care unit (NICU). The patients were observed in three different positions consecutively, each lasting for 4h. The demographic features, cerebral and mesenteric tissue oxygenation with positional changes and feeding periods were recorded. RESULTS: Mean gestational age, mean birth weight and mean postnatal age of the patients were 27.6+/-1.7 weeks, 1046+/-308 g and 42.4+/-15.7 days, respectively. There were no statistically significant differences in cerebral and mesenteric tissue regional SO(2) values in each position (p=0.954 and p=0.151, respectively). The values of cerebral and mesenteric tissue regional SO(2) before and after feeding did not show any statistically significant difference in each position. CONCLUSIONS: Clinically stable very low birth weight infants are able to maintain a stable cerebral and mesenteric tissue oxygenation in different positions, both before and after feeding. Positional changes seem to be safe in VLBW stable infants and this influence should be considered in care of these patients in the NICU. Clinical Trials Identification Number: NCT01255189. PMID- 22088785 TI - Neonatal factors associated with alteration of palatal morphology in very preterm children: the EPIPAGE cohort study. AB - BACKGROUND: Altered palatal morphology has been observed among some preterm children, with possible consequences on chewing, speaking and esthetics, but determinants remain unknown. AIM: To explore the role of neonatal characteristics and neuromotor dysfunction in alteration of palatal morphology at 5 years of age in very preterm children. STUDY DESIGN: Prospective population-based cohort study. SUBJECTS: 1711 children born between 22 and 32 weeks of gestation in 1997 or born between 22 and 26 weeks of gestation in 1998 were included in the study. They all had a medical examination at 5 years of age. OUTCOME MEASURES: Alteration of palatal morphology. RESULTS: The prevalence of altered palatal morphology was 3.7% in the overall sample, 5.1% among boys and 2.2% among girls (adj OR: 2.52; 95%CI: 1.44-4.42). The risk for altered palatal morphology was higher for lower gestational age (adj OR: 0.85; 95%CI: 0.74-0.97 per week), small for-gestational age children (adj OR: 2.11; 95%CI: 1.20-3.72) or children intubated for more than 28 days (adj OR: 3.16; 95%CI: 1.11-8.98). Altered palatal morphology was more common in case of cerebral palsy or moderate neuromotor dysfunction assessed at 5 years. Results were basically the same when neuromotor dysfunction was taken into account, except for intubation. CONCLUSION: Male sex, low gestational age, small-for-gestational age and long intubation have been identified as probable neonatal risk factors for alteration of palatal morphology at 5 years of age in very preterm children. Further studies are needed to confirm these results. PMID- 22088786 TI - Early outcomes of bilateral sequential single lung transplantation after ex-vivo lung evaluation and reconditioning. AB - BACKGROUND: Ex vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard International Society for Heart and Lung Transplantation criteria for transplantation. METHODS: We retrospectively evaluated 13 consecutive EVLP runs between January 2009 and December 2010. Lungs rejected for routine transplantation were implanted to the EVLP circuit and reperfused using acellular supplemented Steen Solution (Vitrolife, Goteborg, Sweden) up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 liters/min/m(2); target left atrial pressure < 5 mm Hg; and pulmonary artery pressure < 15 mm Hg. Mechanical ventilation was introduced after rewarming to 32 degrees C: tidal volume, 6 to 8 ml/kg; respiratory rate, 7 to 8 breaths/min; duration of inspiration/expiration (I/E) ratio, 1:2; and positive end-expiratory pressure, 5 to 10 cm H(2)O. Hemodynamic and respiratory data monitoring with hourly clinical assessment were performed. Donor data, conversion rate to transplantation, and recipient outcome were analyzed. RESULTS: Donor data (n = 13) were: age, 44.23 +/- 8.33 years; female/male, 8:5; cause of death: intracranial hemorrhage, 11 (85%), stroke, 1 (7.5%), hypoxic brain injury, 1 (7.5%); smoking history, 9 (69%), 17.44 +/- 8.92 pack-years; mechanical ventilation, 102.6 +/- 91.92 hours; chest x-ray imaging: abnormal, 12 (92.5%); normal, 1 (7.5%). EVLP: mean 141 +/- 28.83 minutes. Arterial partial pressure of oxygen/fraction of inspired oxygen 100% before termination of the circuit vs pre retrieval value: 57.32 +/- 9.1 vs 42.36 +/- 14.13 kPa (p < 0.05). Six (46%) pairs of donor lungs were transplanted. Median follow-up was 297.5 days (range, 100-390 days), with 100% survival at 3 months. CONCLUSIONS: EVLP may facilitate assessment and/or reconditioning of borderline lungs, with a conversion rate of 46 % and good short-term survival. PMID- 22088787 TI - SETX gene mutation in a family diagnosed autosomal dominant proximal spinal muscular atrophy. AB - Autosomal dominant proximal spinal muscular atrophy (ADSMA) is a rare disorder with unknown gene defects in the majority of families. Here we describe a family where the diagnosis of juvenile and adult onset ADSMA was made in three individuals. Because of retained tendon reflexes an atypical course of juvenile amyotrophic lateral sclerosis (ALS4) was considered. SETX gene sequencing revealed the previously reported heterozygous missense mutation c.1166T50% differential expression of 201 leukocyte transcripts, including upregulated expression of pro-inflammatory and metastasis-related genes. CBSM altered leukocyte expression of 91 genes by >50% at follow-up (group * time interaction), including downregulation of pro inflammatory and metastasis-related genes and upregulation of type I interferon response genes. Promoter-based bioinformatic analyses implicated decreased activity of NF-kappaB/Rel and GATA family transcription factors and increased activity of interferon response factors and the glucocorticoid receptor as potential mediators of CBSM-induced transcriptional alterations. CONCLUSIONS: In early-stage breast cancer patients, a 10-week CBSM intervention can reverse anxiety-related upregulation of pro-inflammatory gene expression in circulating leukocytes. These findings clarify the molecular signaling pathways by which behavioral interventions can influence physical health and alter peripheral inflammatory processes that may reciprocally affect brain affective and cognitive processes. PMID- 22088798 TI - Cord blood levels of thyroid hormones and IGF-1 weakly correlate with breast milk levels of PBDEs in Taiwan. AB - In vivo studies indicate that prenatal or neonatal exposure of rodents to polybrominated diphenyl ethers (PBDEs) disrupts thyroid hormone balance, but few studies have reported an association of PBDEs and insulin-like growth factor 1 (IGF-1). The goal was to examine whether PBDEs exposure affects the levels of thyroid hormones and IGF-1 in cord blood. Study participants were healthy pregnant women recruited from the general population in central Taiwan between 2000 and 2001 and in southern Taiwan from 2007 to 2009. One-hundred-forty-nine breast milk samples (n=149), which were collected within one month after delivery, were analyzed using a high resolution gas chromatograph equipped with a high resolution mass spectrometer. The average and median levels of breast milk Sigma(14)PBDEs were 5.34 and 3.38 ng/g lipid in 2000-2001 and 5.22 and 3.13 ng/g lipid in 2007-2009, respectively. In general, levels of PBDE congeners were very low in this study population and not significantly different between the years 2000-2001 and 2007-2009. Breast milk Sigma(14)PBDEs were not significantly correlated with thyroid hormones and IGF-1 in cord blood. After examining multiple stepwise linear regression models with adjustment for maternal age, pre pregnancy body mass index (BMI), parity, gestational age, and region (namely, central and southern Taiwan), we found that log of T4 in cord blood was significantly but slightly correlated with higher BDE-154 (B=0.113, p=0.017) in breast milk. The log of FT4 concentration was significantly related to a decrease in the log of BDE-99 level (B=-0.137, p=0.043) and an increase in the log of BDE 154 level (B=0.158, p=0.008). Meanwhile, the log of IGF-1 level was also significantly linked to an increase in the log of BDE-196 level (B=0.532, p=0.028) and decrease in the log of BDE-85 level (B=-0.235, p=0.018). Few epidemiological studies report an association between PBDEs exposure and IGF-1. Based on our findings, further in vivo and epidemiological studies are encouraged and needed to explore associations between PBDEs exposure and levels of thyroid hormones and IGF-1. PMID- 22088799 TI - SCIPIO brings new momentum to cardiac cell therapy. PMID- 22088800 TI - Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. AB - BACKGROUND: c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We undertook a phase 1 trial (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO]) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease. METHODS: In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction [EF] <=40%) before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B, patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.gov, number NCT00474461. FINDINGS: This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30.3% (SE 1.9) before CSC infusion to 38.5% (2.8) at 4 months after infusion (p=0.001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30.1% [2.4] at 4 months after CABG vs 30.2% [2.5] at 8 months after CABG). Importantly, the salubrious effects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12.3 ejection fraction units [2.1] vs baseline, p=0.0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32.6 g (6.3) by 7.8 g (1.7; 24%) at 4 months (p=0.004) and 9.8 g (3.5; 30%) at 1 year (p=0.04). INTERPRETATION: These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies. FUNDING: University of Louisville Research Foundation and National Institutes of Health. PMID- 22088801 TI - Relationship of obesity-related disturbances with LH/FSH ratio among post menopausal women in the United States. AB - OBJECTIVES: Although luteinizing hormone to follicular stimulating hormone (LH/FSH) ratio is a controversial criterion for identifying a sub-group of infertile women with polycystic ovary syndrome (PCOS) and abnormalities at the level of the hypothalamic-pituitary-ovarian axis, an elevated LH/FSH ratio is frequently observed in PCOS cases. Obesity and insulin resistance are highly prevalent among PCOS women. To date, no studies have examined the associations of LH/FSH ratio with these co-morbid conditions outside the context of pre- and peri menopausal PCOS women. The objective of this study is to evaluate whether the LH/FSH ratio is associated with obesity, insulin resistance, metabolic disturbances and chronic inflammation among post-menopausal U.S. women, 35-60 years of age. STUDY DESIGN: Cross-sectional study of 693 women who participated in the 1999-2002 National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: Body mass index, waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, systolic and diastolic blood pressures, fasting glucose, metabolic syndrome, Homeostasis Model Assessment for Insulin Resistance and C-reactive protein (CRP). RESULTS: Age- and hysterectomy-adjusted regression models suggest that CRP level is positively associated with LH/FSH ratio and LH/FSH>1, high glucose level and LH/FSH>2 are inversely related and HDL<50mg/dL is positively associated with both LH/FSH>1 and LH/FSH>2. CONCLUSIONS: In a nationally representative sample of post-menopausal women, markers of chronic inflammation and dyslipidemia which are characteristics of PCOS-associated morbidities were also significantly associated with LH/FSH ratio, meriting further investigation. PMID- 22088802 TI - [The exposure method of treatment of burns in children]. AB - Acute burn is a more or less profound destruction of the skin envelope. The depth of the injury determines the severity of functional and aesthetic sequelae. Local care prevents the infection, factor of deepening of the burn. Currently the dressing used in most Burns centers is a bandage covering a bacterial product applied to the burn. The advantage of this dressing is to prevent the occurrence of local infection. In contrast, open-air method of treatment is based on the notions that the wound is infected. His purpose is to reduce the effects of infection by creating an unfavourable environment to the growth and multiplication of bacteria. The principle of this method is the formation over the burned area of an eschar. The eschar acts as a natural dressing to protect the injured area against infection. The residual skin islets are preserved. The surgical cleavage of the eschar is easy; the deep surface of the crust defines the surgical plan. Deep tangential excisions are not necessary. The implementation of this technique is easy and it is particularly well suited to pediatrics. Treatment is not painful and the child's activities are not hampered by bandages. Respect of the children's quality of life and medical-economic efficiency of this method give it a prominent place in the treatment of burns in children. PMID- 22088803 TI - Accuracy of needle biopsy of breast lesions visible on ultrasound: audit of fine needle versus core needle biopsy in 3233 consecutive samplings with ascertained outcomes. AB - INTRODUCTION: Core needle biopsy (CNB) has progressively replaced fine needle aspiration cytology (FNAC) in the diagnosis of breast lesions. Less information is available on how these tests perform for biopsy of ultrasound (US) visible breast lesions. This study examines the outcomes of CNB and FNAC in a large series ascertained with surgical histology or clinical-imaging follow-up. MATERIALS AND METHODS: Retrospective five-year audit of 3233 consecutive US guided needle samplings of solid breast lesions, from self-referred symptomatic or asymptomatic subjects, performed by six radiologists in the same time-frame (2003-2006): 1950 FNAC and 1283 CNB. The probability of undergoing CNB as a first test instead of FNAC was evaluated using logistic regression. Accuracy and inadequacy were calculated for each of CNB and FNAC performed as first test. Accuracy measures included equivocal or borderline/atypical lesions as positive results. RESULTS: The probability of CNB as a first test instead of FNAC increased significantly over time, when there was a pre-test higher level of suspicion, in younger (relative to older) women, with increasing lesion size on imaging, and for palpable (relative to impalpable) lesions. Inadequacy rate was lower for CNB (B1 = 6.9%) than for FNAC (C1 = 17.7%), p < 0.001, and specifically in malignant lesions (B1 = 0.9% vs. C1 = 4.5%; p < 0.001). False negative rate was equally low for both CNB and FNAC (1.7% each test). CNB performed significantly better than FNAC for absolute sensitivity (93.1% vs. 74.4%; p < 0.001) and complete sensitivity (97.4% vs. 93.8%; p = 0.001), however specificity was lower for CNB than FNAC (88.3% vs. 96.4%; p < 0.001). Absolute diagnostic accuracy was higher for CNB than FNAC (84.5% vs. 71.9; p < 0.001) while FNAC performed better than CNB for complete diagnostic accuracy (95.4% vs. 93.2; p < 0.008). In the small subgroup assessed with CNB after an inconclusive initial FNAC (231 cases) there was improved complete sensitivity (from 93.8% to 97.0%) however this also increased costs. CONCLUSION: FNAC and CNB were generally performed in different patients, thus our study reported indirect comparisons of these tests. Although FNAC performed well (except for relatively high inadequacy), CNB had significantly better performance based on measures of sensitivity, but this was associated with lower specificity for CNB relative to FNAC. Overall, CNB is the more reliable biopsy method for sonographically-visible lesions; where FNAC is used as the first-line test, inadequate or inconclusive FNAC can be largely resolved by using repeat sampling with CNB. PMID- 22088804 TI - Quality of life and experience of care in women with metastatic breast cancer: a cross-sectional survey. AB - CONTEXT: Despite developments in the medical management of metastatic breast cancer, little is known about the quality of life (QoL) and experience of care in women with it. OBJECTIVES: To explore QoL, experience of care, and support needs of women living with metastatic breast cancer in the U.K. METHODS: Questionnaire based, cross-sectional study, undertaken in two U.K. cancer centers and online via the Breast Cancer Care website, assessing QoL and experience of care in 235 women with metastatic breast cancer. RESULTS: QoL was assessed using the Functional Assessment of Cancer Therapy--Breast QoL measure. Overall, QoL was low (mean 89.0, standard deviation 21.8) for total score. Low scores were seen uniformly in physical, social, emotional, and functional well-being domains. Symptom burden was a significant problem, with over one-third of women (34%) reporting high levels of pain and other uncontrolled symptoms. In multiple regression analysis, social well-being was significantly better for older women (P<0.001) but was lower in those with bone metastases only (P=0.002). Functional well-being was significantly higher in women without children (P=0.004). Satisfaction with experience of care was low and appeared to be predominantly in the hospital setting, with little evidence of involvement of general practitioners and palliative care services. CONCLUSION: Despite improvements in treatment and survival of women with metastatic breast cancer, this group reports high symptom burden and dissatisfaction with elements of their care, indicating that alternative models of service delivery should be explored. PMID- 22088805 TI - Does hyperglycemia affect the diagnostic value of 18F-FDG PET/CT? AB - BACKGROUND: Net cellular uptake of (18)F-FDG is adversely affected by elevated plasma glucose levels. The purpose of our study was to investigate the influence of hyperglycemic state at the time of (18)F-FDG injection on the diagnostic accuracy of (18)F-FDG PET/CT. METHOD: Pre-scan plasma glucose levels of all patients who were referred for PET/CT with an oncologic indication during the year 2005 were reviewed. All seventy-six patients (50 men, 26 women, mean age +/- SD: 65.5 +/- 9.7 years) with pre-scan glucose level higher than 140 mg/dL (mean plasma glucose level +/- SD: 168.7 +/- 30.8, ranging from 140 to 260 mg/dL) were enrolled into our study. The accuracy of PET/CT scans was assessed using concurrent or follow-up CT, MRI and histologic evidences as well as clinical follow-up as the reference standard. RESULTS: PET/CT was true positive in 37 patients, true-negative in 30 patients, false negative in 6 patients and false positive in 3 patients. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of (18)F-FDG PET/CT on a patient basis were 86%, 90.9%, 92.5%, 83.3% and 88.1%, respectively. Diabetes mellitus was recorded in 50 patients. No significant diagnostic accuracy difference between diabetics and non-diabetics was noticed. CONCLUSION: Our study suggests that (18)F-FDG accumulation of malignant lesions remains sufficiently high for reliable qualitative clinical diagnosis in chronic and acute hyperglycemic states. However, regarding the discordant and inconclusive results of the available reports and the remarkable concerns with reference to the adverse effects of elevated plasma glucose levels on the diagnostic accuracy of (18)F-FDG PET/CT scans, further direct clues seems to be required and should be provided by future studies. PMID- 22088806 TI - Associations between CYP1A1 and CYP2E1 polymorphisms and susceptibility to esophageal cancer in Chaoshan and Taihang areas of China. AB - PURPOSE: To study the causes of esophageal cancer in Chaoshan and Taihang areas. METHODS: By using gel-based DNA microarray genotyping method, four cancer-related polymorphisms including CYP1A1 m2, CYP1A1 m4, CYP2E1 Pst I and CYP2E1 Rsa I were studied with 565 (CYP1A1) or 482 (CYP2E1) cases and 468 (CYP1A1) or 466 (CYP2E1) controls. RESULTS: For CYP1A1 m2, the mutant allele frequencies were 21.3% (Chaoshan) and 19.6% (Taihang), and OR for AG versus AA genotype (Chaoshan) was 1.855 (95% CI [1.227-2.805]). For CYP1A1 m4, no mutant allele was detectable. For CYP2E1 Pst I, the mutant allele frequencies were 27.3% (Chaoshan) and 29.4% (Taihang), and OR for GG versus CC genotype (Taihang) was 3.263 (95% CI [1.059 10.052]). For CYP2E1 Rsa I, the mutant allele frequencies were 27.3% (Chaoshan) and 29.6% (Taihang), and OR for CC versus TT genotype (Taihang) was 3.167 (95% CI [1.026-9.776]). CONCLUSION: The results suggest that AG genotype of CYP1A1 in Chaoshan area and GG (CC) genotype of CYP2E1 in Taihang area are significantly associated with esophageal cancer susceptibility. PMID- 22088807 TI - [Radiation-induced nephropathy]. AB - BACKGROUND: The kidneys are dose-limiting organs when total body irradiation or irradiation of the digestive tract is planned. The incidence of radiation-induced toxicity is probably underestimated due to its latency and confounding factors like chemotherapy. MATERIAL AND METHODS: A search of the literature for radiation induced renal toxicity was performed. RESULTS: Most toxicities occur around 18 months. Renal mobility is significant in terms of dosimetric consequences, in particular in the young child. In case of total body irradiation, the dose responsible for a 5% risk of toxicities is around 16 Gy in 2 Gy fractions over 2 weeks. For partial renal irradiation, the volume receiving 20 Gy should be below 32% of the total renal volume. Compensatory mechanisms remain possible in areas receiving 12 Gy or less in 1 Gy fractions. When nephrotoxic chemotherapy, these tolerance doses must be lowered. Treatment of radiation-induced nephropathy may include ACE inhibitors. DISCUSSION/CONCLUSION: Prospective assessment of dose volume histograms and consideration of renal mobility in treatment plans along with improving radiation techniques should help to improve treatment plans including the kidneys. PMID- 22088808 TI - Mindful maths: reducing the impact of stereotype threat through a mindfulness exercise. AB - Individuals who experience stereotype threat - the pressure resulting from social comparisons that are perceived as unfavourable - show performance decrements across a wide range of tasks. One account of this effect is that the cognitive pressure triggered by such threat drains the same cognitive (or working-memory) resources that are implicated in the respective task. The present study investigates whether mindfulness can be used to moderate stereotype threat, as mindfulness has previously been shown to alleviate working-memory load. Our results show that performance decrements that typically occur under stereotype threat can indeed be reversed when the individual engages in a brief (5 min) mindfulness task. The theoretical implications of our findings are discussed. PMID- 22088809 TI - Genistein reduces heparan sulfate accumulation in human mucolipidosis II skin fibroblasts. AB - Genistein, a soy isoflavone, reduces glycosaminoglycan synthesis and its effect on mucopolysaccharidoses has been tested. In this report, we examined the effect of genistein in human mucolipidosis II skin fibroblasts in vitro. Heparan sulfate was accumulated within both cells and in extracellular spaces in mucolipidosis II. Genistein reduced the amount of heparan sulfate in cultured cells dose dependently and also inhibited cell growth dose dependently. PMID- 22088810 TI - Is celiac axis resection justified for T4 pancreatic body cancer? AB - BACKGROUND: The clinical impact of the distal pancreatectomy with en-bloc celiac axis resection for locally advanced pancreatic body cancer remains unclear. METHODS: We reviewed the records of 13 patients who underwent distal pancreatectomy-celiac axis resection between 1991 and 2009, 58 patients who underwent distal pancreatectomy for pancreatic body cancer involving major vessels, the extrapancreatic neural plexus or other organs (T4 according to the Japanese stage classification) between 1991 and 2009, and 24 patients with unresectable locally advanced pancreatic cancer without distant metastases (unresectable group) between 2001 and 2009. The clinicopathologic factors and overall survival among the 3 groups were compared. RESULTS: The distal pancreatectomy-celiac axis resection group was associated with a significantly higher incidence of morbidity (92% vs 60%, P = .03) and positive surgical margins (69% vs 26%, P = .003) than the distal pancreatectomy group; however, no survival difference was found between the 2 groups. No survivor has lived more than 3 years after operation in the distal pancreatectomy-celiac axis resection group. The distal pancreatectomy-celiac axis resection group had a significantly better prognosis than the unresectable group (median survival time, 20.8 vs 9.8 months; P = .01). CONCLUSION: Aggressive resection for T4 pancreatic body cancer by distal pancreatectomy-celiac axis resection can be justified for otherwise unresectable tumors. The surgical indication should be evaluated carefully because of the higher incidence of morbidity and lower incidence of curability compared with distal pancreatectomy, as well as because there have been no long term survivors so far. PMID- 22088811 TI - Error training: missing link in surgical education. PMID- 22088812 TI - Forging successful interdisciplinary research collaborations: a nationwide survey of departments of surgery. AB - BACKGROUND: Our aim was to estimate the prevalence of academic surgeons engaged in interdisciplinary collaborations and identify success factors and challenges to establishing these collaborations. METHODS: Chairs of surgery at US medical schools and selected hospitals and research institutes were surveyed in 2009 to determine the frequency, types, outcomes, and value of interdisciplinary collaborations; National Institutes of Health funding for these collaborations; major barriers and success factors; and departmental and institutional activities to promote collaborations. RESULTS: Eighty-two department chairs (58%) completed the survey. Ninety-three percent answered that their faculty engaged in interdisciplinary collaborations, and 71% stated that it was critical for their research success. On average, 27% of full-time MDs/MD-PhDs were involved in collaborations compared to 81% of PhDs within their departments. The most frequent collaborators included other clinical (43%) and basic science (24%) departments. Only 5% indicated that their most frequent collaborators were with other university programs, primarily with bioengineering or biomedical engineering. Collaborations resulted most often in publications, research opportunities for surgical residents, and National Institutes of Health funding. Pilot funding and active networking were key success factors. Longer chair tenure was statistically significantly associated with more success factors and fewer barriers to collaborations. Surgeons were much less likely to participate in institution-wide efforts than in departmental activities, although these activities were ongoing in more than two-thirds of institutions. CONCLUSION: Surgeons value collaborations as critical for their research success. Our survey indicates the potential for additional collaborations through more involvement with institutional efforts and with other university faculty. Stable, supportive department chairs are critical to establishing these activities. PMID- 22088813 TI - Incisional hernia after abdominal closure with slowly absorbable versus fast absorbable, antibacterial-coated sutures. AB - BACKGROUND: Incisional hernia remains among the most common complications after midline incision of the abdominal wall. The role of the suture material used for abdominal wall closure remains controversial. To decrease bacterial adherence to surgical sutures, braided suture materials with antibacterial activity (Vicryl plus, Ethicon, Inc) were developed. This is the first study to analyze long-term results using an antibacterial-braided suture material for abdominal wall closure in a large clinical trial. METHODS: To analyze the effects of Triclosan-coated suture material (Vicryl plus) on the development of incisional hernia, we performed a 36-month follow-up of 1,018 patients who had a primary midline incision for elective abdominal surgery. In the first time period, a PDS II loop suture was used. In the second observation period, we used Vicryl plus. All variables were recorded prospectively in a database. The primary outcome was the number of incisional hernias. Risk factors for the development of incisional hernias were collected prospectively to compare the 2 groups. RESULTS: The overall incisional hernia rate in the 36-month follow-up period was 14.6%. Analyzing the influence of the suture material used on the development of incisional hernia, we did not find differences between the 2 groups (PDS II, 14%; Vicryl plus, 15.2%). In the multivariate analysis of possible factors in the study population, only body mass index (BMI) showed a significant influence on the development of incisional hernias. Despite the incidence of wound infections being less in the Vicryl plus group (6.1% vs 11.9%; P < .05), there were no difference in incidence of incisional hernia between the 2 groups. CONCLUSION: Fast absorbable sutures with antibacterial coating (Tricosan) do not increase the hernia rate after midline abdominal incision compared with slowly absorbable sutures, when wound infection rates are decreased by coating the fast absorbable suture with Triclosan. The development of incisional hernia is significantly increasing in patients with a BMI >30 kg/m(2). PMID- 22088814 TI - Decrease in donor heart injury by recombinant clusterin protein in cold preservation with University of Wisconsin solution. AB - BACKGROUND: Donor organ injury during cold preservation before transplantation negatively impacts graft survival. Clusterin (CLU) is a chaperonic protein, and its expression confers donor hearts resistance to cold ischemic injury. This study was conducted to evaluate if the supplement of recombinant CLU protein (rCLU) protects donor organs from injury during cold storage with University of Wisconsin (UW) solution. METHODS: Human endothelial cell cultures were used as an in vitro model. Heart transplantation in mice was used as an in vivo model. Cell membrane disruption or death was indicated by the release of lactate dehydrogenase (LDH). Donor injury was determined by its functional recovery, and histologic and biochemical analyses. RESULTS: Supplement of rCLU to UW solution protected cultured human endothelial cells from cold-induced cell necrosis, as evidenced by a decrease in both release of LDH and the number of ethidium bromide stained necrotic cells. The protective activity of rCLU was associated with enhanced membrane fluidity at cold temperature. During cold storage of heart organs in UW solution, supplemental rCLU significantly decreased LDH release from heart tissue. In a preclinical model of transplantation, heart grafts after cold preservation with rCLU-containing UW solution had better functional recovery and decreased perivascular inflammation, neutrophil infiltration, and cardiac cell death, including apoptosis and necrosis, that correlated with lower levels of serum creatine kinase and LDH in recipients. CONCLUSION: Our data suggest that supplement of CLU protein in a cold preservation solution may have potential in improving cold preservation of donor organs in transplantation. PMID- 22088816 TI - Accidental discovery: the polytetrafluoroethylene graft. PMID- 22088815 TI - Pretreating mesenchymal stem cells with interleukin-1beta and transforming growth factor-beta synergistically increases vascular endothelial growth factor production and improves mesenchymal stem cell-mediated myocardial protection after acute ischemia. AB - BACKGROUND: Mesenchymal stem cells (MSCs) improve postischemic myocardial function in part through their secretion of growth factors such as vascular endothelial growth factor (VEGF). Pretreating MSCs with various cytokines or small molecules can improve VEGF secretion and MSC-mediated cardioprotection. However, whether 1 cytokine can potentiate the effect of another cytokine in MSC pretreatment to achieve a synergistic effect on VEGF production and cardioprotection is poorly studied. METHODS: MSCs were treated with interleukin (IL)-1beta and/or transforming growth factor (TGF)-beta1 for 24 hours before experiments. VEGF production was determined by enzyme-linked immunosorbent assay. Isolated hearts from adult male Sprague-Dawley rats were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes reperfusion. Hearts (n = 5-7 per group) were randomly infused with vehicle, untreated MSCs, or MSCs pretreated with IL-1beta and/or TGF-beta1. Specific inhibitors were used to delineate the roles of p38 mitogen-activated protein kinase (MAPK) and SMAD3 in IL-1beta- and TGF-beta1-mediated stimulation of MSCs. RESULTS: MSCs cotreated with IL-1beta and TGF-beta1 exhibited synergistically increased VEGF secretion, and they greatly improved postischemic myocardial functional recovery. Ablation of p38 MAPK and SMAD3 activation with specific inhibitors negated both IL-1beta- and TGF-beta1-mediated VEGF production in MSCs and the ability of these pretreated MSCs to improve myocardial recovery after ischemia. CONCLUSION: Pretreating MSCs with 2 cytokines may be useful to fully realize the potential of cell-based therapies for ischemic tissues. PMID- 22088818 TI - The experience of burnout across different surgical specialties in the United Kingdom: a cross-sectional survey. AB - BACKGROUND: We used a cross-sectional e-mail survey to assess the prevalence of psychological morbidity across different surgical specialties and identify predictor variables of burnout in surgeons. METHOD: The survey was sent to 1971 surgeons from 127 National Health Service (NHS) hospital trusts across the United Kingdom. Burnout prevalence and mood were assessed using the Maslach Burnout Inventory-General Survey and Profile of Mood States (POMS), respectively. Demographic and POMS factors were investigated as predictors of burnout using linear and stepwise regression analyses. RESULTS: Responses to the survey were received from 342 surgeons (17% response rate). One-third of 313 respondents showed high mean levels of burnout on exhaustion (2.32; standard deviation [SD], 1.62) and cynicism (2.34; SD, 1.44) subscales. Some specialties worked significantly more hours per week (F[8, 252] = 2.89; P = .004), but burnout prevalence did not differ significantly between specialty, grade, age, gender, hours worked per week, or years spent in post. The number of years in specialty (beta = -0.17; P = .003) independently predicted surgeons' scores on exhaustion. POMS factors significantly predicted burnout, where fatigue (beta = 0.58; P < .001) was the best predictor of exhaustion scores, depression (beta = 0.28; P < .001) the best predictor of cynicism, and vigor (beta = 0.29; P < .001) the best predictor of professional efficacy. Management issues were cited as contributing to psychological morbidity. CONCLUSION: UK surgeons show high levels of cynicism and exhaustion burnout irrespective of their specialty, grade, or hours worked per week. Surgeons' mood profiles significantly predicted burnout, indicating the POMS could be used as part of an assessment for preventive interventions. NHS management and infrastructure are highlighted as influences on surgeons' psychological health. PMID- 22088817 TI - The outcome of resected cystic pancreatic endocrine neoplasms: a case-matched analysis. AB - INTRODUCTION: Cystic pancreatic endocrine neoplasms (CPENs) are uncommon tumors with uncertain disease biology and ill-defined diagnostic features. METHODS: A prospectively maintained pancreatic cyst registry was queried, and 31 cases of CPEN that were resected between 1995 and 2010 were identified. Patient and lesion characteristics were detailed and compared with resected non-PEN cystic lesions. Recurrence and survival outcome were compared with 31 noncystic PENs matched for functional status, differentiation, size, World Health Organization classification, grade, and presence of metastases. RESULTS: During the study period, CPENs accounted for 7% of resected pancreatic cysts (31/469) and 12% of resected PENs (31/255). CPENs were primarily sporadic (94%), solitary (87%), nonfunctioning (100%), and incidentally discovered (68%). The median diameter was 2.1 cm (range, 0.9-6.2 cm), and preoperative imaging identified septations in 29%, a solid component in 26%, and cyst wall enhancement or a characteristic hypervascular rim in 45% of cases. Preoperative imaging and/or cytology suggested the diagnosis of CPEN in 61%. Compared with resected nonendocrine cystic lesions, CPEN were less frequently symptomatic, less likely to contain septations, and smaller. Compared with matched noncystic PENs, CPENs had comparable demographic, radiologic, and pathologic features and statistically similar long-term outcome (5-year disease-free survival: CPEN: 100% vs PEN: 86%, P = .947). CONCLUSION: In this study, CPENs were primarily asymptomatic small lesions that could be characterized in the majority of cases by cyst wall enhancement on preoperative imaging and/or cytologic assessment. No significant difference in recurrence or survival outcome was identified between cystic and noncystic PENs. PMID- 22088819 TI - Evaluation of the International Study Group of Pancreatic Surgery definition of post-pancreatectomy hemorrhage in a high-volume center. AB - BACKGROUND: Although postpancreatectomy hemorrhage (PPH) is observed infrequently after pancreatic surgery, it remains a serious complication with a high rate of mortality. Recently, the International Study Group of Pancreatic Surgery (ISGPS) issued a new definition for PPH. To evaluate and validate this new definition, we analyzed data retrospectively from our center. METHODS: Data from 945 patients who underwent pancreatic surgery in our department between October 1993 and December 2009 were identified retrospectively from our prospective database with regard to the occurrences of PPH. We graded the hemorrhages recorded in our database according to the ISGPS consensus definition. We assessed the clinical course, morbidity, mortality, and duration of hospital stay for patients with grade B and C PPHs in comparison with patients who underwent pancreatic resections without hemorrhage. RESULTS: Grade B PPH after pancreatic surgery occurred in 16 patients (1.7%), and grade C PPH occurred in 38 patients (4.0%). Mortality was significantly increased in PPH grades B and C compared with control patients (25.9% vs 2.0%; P < .001) and contributed to nearly one-half of the mortality in the present series. Morbidity was also increased in patients with grade B (76.5%) and C (94.6%) PPH compared with control patients (59.6%; P < .001). Grade B and C PPH correlated significantly with the incidence of grade C postoperative pancreatic fistula (14.8% vs 1.9%), grade C delayed gastric emptying (18.5% vs 4.0%), and wound infection (38.9% vs 13.5%) compared with control patients. CONCLUSION: This is the first clinical evaluation of the ISGPS PPH definition. Our data indicate that the new definition correlates well with morbidity, mortality, and duration of hospital stay. The definition, therefore, seems suitable for clinical and scientific applications. PMID- 22088820 TI - NBCA medical adhesive (n-butyl-2-cyanoacrylate) versus suture for patch fixation in Lichtenstein inguinal herniorrhaphy: a randomized controlled trial. AB - BACKGROUND: We compared the effectiveness of n-butyl-2-cyanoacrylate (NBCA) and traditional suture for patch fixation in Lichtenstein tension-free herniorrhaphy for inguinal hernias. METHODS: A total of 110 patients with primary unilateral inguinal hernia were assigned randomly to either experimental or control groups. In the experimental group, NBCA adhesive was used during Lichtenstein herniorrhaphy; traditional suture was used in the control group. We evaluated operation time, postoperative duration of stay, visual analogue scale (VAS) pain score, incidence of chronic pain and hematoma formation, and hernia recurrence. RESULTS: There was no hernia recurrence or wound infection in either group. In the experimental group, 2 local hematomas occurred while no patients experienced chronic postoperative pain; in the control group, 10 hematomas occurred, and 6 patients experienced chronic pain. There was no difference in postoperative duration of stay between the groups (P > .05), but the experimental group had a lesser operation time and postoperative VAS score (P < .05). CONCLUSION: The use of NBCA medical adhesive in tension-free inguinal herniorrhaphy is effective and safe. PMID- 22088821 TI - Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) results in profound weight loss and resolution of type 2 diabetes mellitus (T2DM). The mechanism of this remarkable transition remains poorly defined. It has been proposed that endotoxin (lipopolysaccharide [LPS]) sets inflammatory tone, triggers weight gain, and initiates T2DM. Because RYGB may diminish LPS from endogenous and exogenous sources, we hypothesized that LPS and the associated cascade of oxidative and inflammatory stress would diminish after RYGB. METHODS: Fifteen adults with morbid obesity and T2DM undergoing RYGB were studied. After an overnight fast, a baseline blood sample was collected the morning of surgery and at 180 days to assess changes in glycemia, insulin resistance, LPS, mononuclear cell nuclear factor (NF)-kappaB binding and mRNA expression of CD14, TLR-2, TLR-4, and markers of inflammatory stress. RESULTS: At 180 days after RYGB, subjects had a significant decrease in body mass index (52.1 +/- 13.0 to 40.4 +/- 11.1), plasma glucose (148 +/- 8 to 101 +/- 4 mg/dL), insulin (18.5 +/- 2.2 mMUU/mL to 8.6 +/- 1.0 mMUU/mL) and HOMA-IR (7.1 +/- 1.1 to 2.1 +/- 0.3). Plasma LPS significantly reduced by 20 +/- 5% (0.567 +/- 0.033 U/mL to 0.443 +/- 0.022 E U/mL). NF-kappaB DNA binding decreased significantly by 21 +/- 8%, whereas TLR-4, TLR-2, and CD-14 expression decreased significantly by 25 +/- 9%, 42 +/- 8%, and 27 +/- 10%, respectively. Inflammatory mediators CRP, MMP-9, and MCP-1 decreased significantly by 47 +/- 7% (10.7 +/- 1.6 mg/L to 5.8 +/- 1.0 mg/L), 15 +/- 6% (492 +/- 42 ng/mL to 356 +/- 26 ng/mL) and 11 +/- 4% (522 +/- 35 ng/mL to 466 +/- 35 ng/mL), respectively. CONCLUSION: LPS, NF-kappaB DNA binding, TLR-4, TLR-2, and CD14 expression, CRP, MMP-9, and MCP-1 decreased significantly after RYGB. The mechanism underlying resolution of insulin resistance and T2DM after RYGB may be attributable, at least in part, to the reduction of endotoxemia and associated proinflammatory mediators. PMID- 22088822 TI - Heme oxygenase-1 regulates the JNK signaling pathway through the MLK3-MKK7-JNK3 signaling module in brain ischemia injury. AB - Although previous researches indicated that heme oxygenase-1 (HO-1) plays a conspicuous role in neuronal injury induced by reperfusion following the brain ischemia, reasonable mechanisms for the role of HO-1 are not clear. In this work, we investigated whether HO-1 was involved in the regulation of the c-Jun N terminal kinase (JNK) signaling pathway and neuronal cell injury induced by the brain ischemia followed by reperfusion. Cobaltic protoporphyrin (CoPP), an activator of HO-1, was administrated to induce the overexpression of HO-1 by intracerebroventricular infusion 20 min before ischemia. The results showed that the combination of HO-1-mixed lineage kinase 3 (MLK3), MLK3-mitogen-activated kinase kinase 7 (MKK7) and MKK7-JNK3 increased to a peak at 6h of reperfusion following 15 min of ischemia induced by four-vessel occlusion in rats, and these effects were downregulated by CoPP. In addition, CoPP could inhibit the activation of JNK3, c-Jun and caspase-3. Furthermore, pretreatment with CoPP significantly increased the survival of neurons after 5 days of reperfusion. In contrast, all of the above effects of CoPP were reversed by zinc protoporphyrin (ZnPP), a selective inhibitor of HO-1. Our results suggested that HO-1 could protect neurons against brain ischemic injury by downregulating the JNK signaling pathway through the MLK3-MKK7-JNK3 signaling module. PMID- 22088824 TI - Baicalin promotes neuronal differentiation of neural stem/progenitor cells through modulating p-stat3 and bHLH family protein expression. AB - Signal transducer and activator of transcription 3 (stat3) and basic helix-loop helix (bHLH) gene family are important cellular signal molecules for the regulation of cell fate decision and neuronal differentiation of neural stem/progenitor cells (NPCs). In the present study, we investigated the effects of baicalin, a flavonoid compound isolated from Scutellaria baicalensis G, on regulating phosphorylation of stat3 and expression of bHLH family proteins and promoting neuronal differentiation of NPCs. Embryonic NPCs from the cortex of E15 16 rats were treated with baicalin (2, 20 MUM) for 2h and 7 days. Neuronal and glial differentiations were identified with mature neuronal marker microtubule associated protein (MAP-2) and glial marker Glial fibrillary acidic protein (GFAP) immunostaining fluorescent microscopy respectively. Phosphorylation of stat3 (p-stat3) and expressions of bHLH family genes including Mash1, Hes1 and NeuroD1 were detected with immunofluorescent microscopy and Western blot analysis. The results revealed that baicalin treatment increased the percentages of MAP-2 positive staining cells and decreased GFAP staining cells. Meanwhile, baicalin treatment down-regulated the expression of p-stat3 and Hes1, but up regulated the expressions of NeuroD1 and Mash1. Those results indicate that baicalin can promote the neural differentiation but inhibit glial formation and its neurogenesis-promoting effects are associated with the modulations of stat3 and bHLH genes in neural stem/progenitor cells. PMID- 22088823 TI - Dihydrotestosterone differentially modulates the cortisol response of the hypothalamic-pituitary-adrenal axis in male and female rhesus macaques, and restores circadian secretion of cortisol in females. AB - Here we used a within-subject design to evaluate hypothalamic-pituitary-adrenal (HPA) activity following replacement of low and high physiological levels of testosterone (T) to adult, gonadally-suppressed, male rhesus macaques, and replacement with sex-specific low and high physiological doses of dihydrotestosterone (DHT) in the same adult males as well as in adult, gonadally suppressed, female rhesus macaques. As indexes of HPA axis activation following T and DHT replacement, serum levels of cortisol (CORT) were measured before and following dexamethasone (DEX) inhibition, and corticotrophin-releasing factor (CRF) induced activation. Female monkeys were assessed for differences in response associated with dominant (DOM) and subordinate (SUB) social status. Data show that the high physiological dose of DHT significantly decreased basal CORT in both male and female monkeys irrespective of social status, but reduced CRF stimulated CORT only in males. SUB female monkeys showed a trend towards increased CRF-stimulated CORT release under high-dose DHT replacement compared to DOM females or males given the same treatment, indicating that androgens likely have no influence on reducing HPA activation under chronic psychosocial stress in females. The normal circadian rhythm of CORT release was absent in placebo replaced SUB and DOM females and was restored with low-dose DHT replacement. These results indicate that DHT significantly reduces CRF-stimulated CORT release only in male monkeys, and plays a role in maintaining circadian changes in CORT release in female monkeys. PMID- 22088825 TI - Brain potentials show rapid activation of implicit attitudes towards young and old people. AB - While previous behavioural research suggests that attitudes, for example towards elderly people, may be activated automatically, this type of research does not provide information about the detailed time-course of such processing in the brain. We investigated the impact of age related attitude information in a Go/NoGo association task that paired photographs of elderly or young faces with positive or negative words. Event related brain potentials showed an N200 (NoGo) component, which appeared earlier in runs which required similar responses for congruent stimulus pairings (e.g. respond to pictures of elderly faces or negative words) than for incongruent pairings (e.g. respond to elderly faces or positive words). As information processing leading to a certain attitude must precede differential brain activity according to the congruence of the paired words and faces, we show that this type of information is activated almost immediately following the structural encoding of the face, between 170 and 230 ms after onset of the face. PMID- 22088826 TI - Perceived social support as a predictor of disease-specific quality of life in head-and-neck cancer patients. AB - BACKGROUND: Treatment for head-and-neck cancer (HNC) can lead to severe decrements in disease-specific quality of life (DSQOL) due to disfigurement and disability in speech, eating, and/or breathing. Psychosocial factors such as social support may explain individual variance in DSQOL outcomes. OBJECTIVE: The researchers sought to evaluate changes in perceived availability of social support from pretreatment to posttreatment and to determine whether decreases in perceived social support predicted poorer posttreatment DSQOL among HNC patients, controlling for disease- and treatment-related factors. METHODS: Participants (n = 32) were newly diagnosed with HNC and were awaiting surgery and/or radiation treatment. Measures included the ENRICHD Social Support instrument (ESSI) to assess perceived social support and the Functional Assessment of Cancer Therapy Head & Neck (FACT-H&N) to assess DSQOL. Paired-samples t-tests and hierarchical regression analyses were conducted to determine relationships between pretreatment and posttreatment perceived social support and DSQOL. RESULTS: Perceived social support decreased significantly from pre- to posttreatment (F[31] = -2.71, P < .01). After adjusting for relevant covariates and pretreatment DSQOL, change in perceived social support remained a significant predictor of posttreatment DSQOL (beta = .47, P < .01). LIMITATIONS: This study included a relatively small sample of HNC patients, which limited power to evaluate mechanisms of observed relationships. CONCLUSIONS: Increased social isolation may be a risk factor for poorer physical recovery from, or adjustment to, treatment-related side effects. Social support may be an important target for psychosocial interventions for patients who face challenging treatment side effects. PMID- 22088827 TI - The attitudes of nurses toward opioid analgesics at a hospital in Colombia. PMID- 22088828 TI - The role of spirituality and religious coping in the quality of life of patients with advanced cancer receiving palliative radiation therapy. AB - OBJECTIVES: National palliative care guidelines outline spiritual care as a domain of palliative care, yet patients' religiousness and/or spirituality (R/S) are underappreciated in the palliative oncology setting. Among patients with advanced cancer receiving palliative radiation therapy (RT), this study aims to characterize patient spirituality, religiousness, and religious coping; examine the relationships of these variables to quality of life (QOL); and assess patients' perceptions of spiritual care in the cancer care setting. METHODS: This is a multisite, cross-sectional survey of 69 patients with advanced cancer (response rate = 73%) receiving palliative RT. Scripted interviews assessed patient spirituality, religiousness, religious coping, QOL (McGill QOL Questionnaire), and perceptions of the importance of attention to spiritual needs by health providers. Multivariable models assessed the relationships of patient spirituality and R/S coping to patient QOL, controlling for other significant predictors of QOL. RESULTS: Most participants (84%) indicated reliance on R/S beliefs to cope with cancer. Patient spirituality and religious coping were associated with improved QOL in multivariable analyses (beta = 10.57, P < .001 and beta = 1.28, P = .01, respectively). Most patients considered attention to spiritual concerns an important part of cancer care by physicians (87%) and nurses (85%). LIMITATIONS: Limitations include a small sample size, a cross sectional study design, and a limited proportion of nonwhite participants (15%) from one US region. CONCLUSION: Patients receiving palliative RT rely on R/S beliefs to cope with advanced cancer. Furthermore, spirituality and religious coping are contributors to better QOL. These findings highlight the importance of spiritual care in advanced cancer care. PMID- 22088829 TI - Validity of affect measurements in evaluating symptom reporting in athletes. AB - Identifying factors that improve the assessment of athletes' psychological functioning is imperative to make proper return-to-play decisions following concussion. Prior research indicates that an individual's affect is related to symptom reporting. The present study examines two novel methods of affect assessment in college athletes at baseline participating in a sports-concussion management program. A total of 256 athletes completed a neuropsychological baseline battery with measurements of psychological symptoms (BDI-Fast Screen, Post-Concussion Symptom Scale, and ImPact Total Symptom Score) and a measure of affective memory bias (the Affective Verbal Learning Test; AVLT). Examiners completed an observation-based rating of affect. Multivariate analysis of variance and chi2 analyses were conducted to examine the effect of affect on symptom reports. Examiners' Affect Ratings were predictive of broad symptom reporting, while the performance based index of affect (Affective Verbal Learning Test, AVLT) was more predictive of depressive symptoms. These findings suggest that performance on the AVLT may be a useful indicator of self-reported depression in a collegiate athlete sample. Additionally, these results demonstrate that examiners' behavioral assessments of affect are important in the assessment of psychological functioning in athletes. Continued work should focus on developing objective measures that are sensitive and valid for the evaluation of outcomes from concussion. PMID- 22088830 TI - Strong evidence in support of CT colonography screening. PMID- 22088832 TI - Thallium concentrations and sources in the surface sediments of Bohai Bay. AB - The Tl concentrations and chemical speciation were determined in the surface sediments of Bohai Bay to evaluate its biogeochemical characteristics. The total Tl concentrations were in the range of 0.506-0.770 MUg/g and correlated significantly with clay and total organic carbon (TOC) contents, suggesting that the grain size and TOC were major factors controlling Tl distribution. The sequential extraction performed to indicate Tl speciation and availability in Bohai Bay sediments suggested that Tl occurred mainly in the residual fraction and Tl came mainly from natural input. In the non-residual fractions, Fe-Mn oxide and organic matter fractions accounted for the main portions, suggesting that the labile Tl adsorption was dominated by Fe-Mn oxides and organic matter. In addition, according to our estimate, about 2.7 t/yr and 0.16 t/yr of Tl reached Bohai Bay via rivers and atmosphere, respectively. PMID- 22088831 TI - Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: a randomised controlled trial. AB - BACKGROUND: Screening for colorectal cancer is widely recommended, but the preferred strategy remains unidentified. We aimed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography. METHODS: Members of the general population, aged 50-75 years, and living in the regions of Amsterdam or Rotterdam, identified via the registries of the regional municipal administration, were randomly allocated (2:1) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography. Randomisation was done per household with a minimisation algorithm based on age, sex, and socioeconomic status. Invitations were sent between June 8, 2009, and Aug 16, 2010. Participants assigned to CT colonography who were found to have one or more large lesions (>=10 mm) were offered colonoscopy; those with 6-9 mm lesions were offered surveillance CT colonography. The primary outcome was the participation rate, defined as number of invitees undergoing the examination relative to the total number of invitees. Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees. Invitees and screening centre employees were not masked to allocation. This trial is registered in the Dutch trial register, number NTR1829. FINDINGS: 1276 (22%) of 5924 colonoscopy invitees participated, compared with 982 (34%) of 2920 CT colonography invitees (relative risk [RR] 1.56, 95% CI 1.46-1.68; p<0.0001). Of the participants in the colonoscopy group, 111 (9%) had advanced neoplasia of whom seven (<1%) had a carcinoma. Of CT colonography participants, 84 (9%) were offered colonoscopy, of whom 60 (6%) had advanced neoplasia of whom five (<1%) had a carcinoma; 82 (8%) were offered surveillance. The diagnostic yield for all advanced neoplasia was 8.7 per 100 participants for colonoscopy versus 6.1 per 100 for CT colonography (RR 1.46, 95% CI 1.06-2.03; p=0.02) and 1.9 per 100 invitees for colonoscopy and 2.1 per 100 invitees for CT colonography (RR 0.91, 0.66-2.03; p=0.56). The diagnostic yield for advanced neoplasia of 10 mm or more was 1.5 per 100 invitees for colonoscopy and 2.0 per 100 invitees for CT colonography, respectively (RR 0.74, 95% CI 0.53-1.03; p=0.07). Serious adverse events related to the screening procedure were post polypectomy bleedings: two in the colonoscopy group and three in the CT colonography group. INTERPRETATION: Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography. The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies, indicating that both techniques can be used for population-based screening for colorectal cancer. Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable. FUNDING: Netherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation. PMID- 22088833 TI - Women with prior preterm birth and short cervical length: to cerclage or not? PMID- 22088834 TI - Women with prior preterm birth and short cervix: do NOT cerclage. PMID- 22088835 TI - Cerclage decreases preterm birth: finally the level I evidence is here. PMID- 22088837 TI - The rate of cervical change and the phenotype of spontaneous preterm birth. AB - OBJECTIVE: Preterm birth is classified by the presence of uterine contractions and/or amniorrhexis at clinical presentation. This classification does not include prior cervical change. We hypothesized that the rate of cervical shortening before preterm birth would not differ according to clinical presentation. STUDY DESIGN: We analyzed data from a completed study of paired cervical ultrasound measurements to test our hypothesis. Cervical ultrasound measurements obtained 4 weeks apart in the second trimester were related to gestational age and clinical presentation at birth. RESULTS: Of 2521 eligible women, 128 were delivered after preterm labor and 106 after preterm membrane rupture; 89 delivered preterm for a medical or obstetrical indication; 2198 delivered at term. The rate of change was similar in women who presented with preterm labor (-0.96 mm/week) and preterm ruptured membranes (-0.82 mm/week). CONCLUSION: Cervical shortening occurs at the same rate before spontaneous preterm birth, regardless of presentation. PMID- 22088838 TI - Silent existence: a retroperitoneal tumor had an unexpected origin. PMID- 22088839 TI - Outpatient balloon vaginoplasty for treatment of vaginal aplasia: retropubic balloon vaginoplasty was performed as an office procedure under local anesthesia. AB - We evaluated the feasibility and operative and postoperative outcomes of office balloon vaginoplasty. Office balloon vaginoplasty was performed successfully for a case with vaginal aplasia. She was currently married and presenting with minimal penetration and dyspareunia. We successfully performed the procedure through retro-pubic space under local anesthesia within 25 min total operative time and it was well tolerated by the patient. No operative complications were reported. The resulting neovagina was cosmetically attractive and 10 cm in depth. Sexual intercourse was started on the day of catheter removal. Penetration and satisfaction scores increased up to 90 points for both partners. PMID- 22088840 TI - Discussion: 'Bacterial vaginosis and STI risk' by Allsworth et al. PMID- 22088841 TI - NoRSE: noise reduction and state evaluator for high-frequency single event traces. AB - NoRSE was developed to analyze high-frequency datasets collected from multistate, dynamic experiments, such as molecular adsorption and desorption onto carbon nanotubes. As technology improves sampling frequency, these stochastic datasets become increasingly large with faster dynamic events. More efficient algorithms are needed to accurately locate the unique states in each time trace. NoRSE adapts and optimizes a previously published noise reduction algorithm and uses a custom peak flagging routine to rapidly identify unique event states. The algorithm is explained using experimental data from our lab and its fitting accuracy and efficiency are then shown with a generalized model of stochastic datasets. The algorithm is compared to another recently published state finding algorithm and is found to be 27 times faster and more accurate over 55% of the generalized experimental space. NoRSE is written as an M-file for Matlab. AVAILABILITY: http://web.mit.edu/stranogroup/NoRSE.txt. PMID- 22088842 TI - Dragon PolyA Spotter: predictor of poly(A) motifs within human genomic DNA sequences. AB - MOTIVATION: Recognition of poly(A) signals in mRNA is relatively straightforward due to the presence of easily recognizable polyadenylic acid tail. However, the task of identifying poly(A) motifs in the primary genomic DNA sequence that correspond to poly(A) signals in mRNA is a far more challenging problem. Recognition of poly(A) signals is important for better gene annotation and understanding of the gene regulation mechanisms. In this work, we present one such poly(A) motif prediction method based on properties of human genomic DNA sequence surrounding a poly(A) motif. These properties include thermodynamic, physico-chemical and statistical characteristics. For predictions, we developed Artificial Neural Network and Random Forest models. These models are trained to recognize 12 most common poly(A) motifs in human DNA. Our predictors are available as a free web-based tool accessible at http://cbrc.kaust.edu.sa/dps. Compared with other reported predictors, our models achieve higher sensitivity and specificity and furthermore provide a consistent level of accuracy for 12 poly(A) motif variants. CONTACT: vladimir.bajic@kaust.edu.sa SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22088843 TI - Inferring gene regulatory networks from gene expression data by path consistency algorithm based on conditional mutual information. AB - MOTIVATION: Reconstruction of gene regulatory networks (GRNs), which explicitly represent the causality of developmental or regulatory process, is of utmost interest and has become a challenging computational problem for understanding the complex regulatory mechanisms in cellular systems. However, all existing methods of inferring GRNs from gene expression profiles have their strengths and weaknesses. In particular, many properties of GRNs, such as topology sparseness and non-linear dependence, are generally in regulation mechanism but seldom are taken into account simultaneously in one computational method. RESULTS: In this work, we present a novel method for inferring GRNs from gene expression data considering the non-linear dependence and topological structure of GRNs by employing path consistency algorithm (PCA) based on conditional mutual information (CMI). In this algorithm, the conditional dependence between a pair of genes is represented by the CMI between them. With the general hypothesis of Gaussian distribution underlying gene expression data, CMI between a pair of genes is computed by a concise formula involving the covariance matrices of the related gene expression profiles. The method is validated on the benchmark GRNs from the DREAM challenge and the widely used SOS DNA repair network in Escherichia coli. The cross-validation results confirmed the effectiveness of our method (PCA-CMI), which outperforms significantly other previous methods. Besides its high accuracy, our method is able to distinguish direct (or causal) interactions from indirect associations. AVAILABILITY: All the source data and code are available at: http://csb.shu.edu.cn/subweb/grn.htm. CONTACT: lnchen@sibs.ac.cn; zpliu@sibs.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22088844 TI - Time-course network analysis reveals TNF-alpha can promote G1/S transition of cell cycle in vascular endothelial cells. AB - MOTIVATION: Tumor necrosis factor-alpha (TNF-alpha), a major inflammatory cytokine, is closely related to several cardiovascular pathological processes. However, its effects on the cell cycle of vascular endothelial cells (VECs) have been the subject of some controversy. To investigate the molecular mechanism underlying this process, we constructed time-course protein-protein interaction (PPI) networks of TNF-alpha induced regulation of cell cycle in VECs using microarray datasets and genome-wide PPI datasets. Then, we analyzed the topological properties of the responsive PPI networks and calculated the node degree and node betweenness centralization of each gene in the networks. We found that p21, p27 and cyclinD1, key genes of the G1/S checkpoint, are in the center of responsive PPI networks and their roles in PPI networks are significantly altered with induction of TNF-alpha. According to the following biological experiments, we proved that TNF-alpha can promote G(1)/S transition of cell cycle in VECs and facilitate the cell cycle activation induced by vascular endothelial growth factor. CONTACT: shaoli@mail.tsinghua.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22088845 TI - TREAT: a bioinformatics tool for variant annotations and visualizations in targeted and exome sequencing data. AB - TREAT (Targeted RE-sequencing Annotation Tool) is a tool for facile navigation and mining of the variants from both targeted resequencing and whole exome sequencing. It provides a rich integration of publicly available as well as in house developed annotations and visualizations for variants, variant-hosting genes and host-gene pathways. AVAILABILITY AND IMPLEMENTATION: TREAT is freely available to non-commercial users as either a stand-alone annotation and visualization tool, or as a comprehensive workflow integrating sequencing alignment and variant calling. The executables, instructions and the Amazon Cloud Images of TREAT can be downloaded at the website: http://ndc.mayo.edu/mayo/research/biostat/stand-alone-packages.cfm. PMID- 22088846 TI - QuRe: software for viral quasispecies reconstruction from next-generation sequencing data. AB - SUMMARY: Next-generation sequencing (NGS) is an ideal framework for the characterization of highly variable pathogens, with a deep resolution able to capture minority variants. However, the reconstruction of all variants of a viral population infecting a host is a challenging task for genome regions larger than the average NGS read length. QuRe is a program for viral quasispecies reconstruction, specifically developed to analyze long read (>100 bp) NGS data. The software performs alignments of sequence fragments against a reference genome, finds an optimal division of the genome into sliding windows based on coverage and diversity and attempts to reconstruct all the individual sequences of the viral quasispecies--along with their prevalence--using a heuristic algorithm, which matches multinomial distributions of distinct viral variants overlapping across the genome division. QuRe comes with a built-in Poisson error correction method and a post-reconstruction probabilistic clustering, both parameterized on given error rates in homopolymeric and non-homopolymeric regions. AVAILABILITY: QuRe is platform-independent, multi-threaded software implemented in Java. It is distributed under the GNU General Public License, available at https://sourceforge.net/projects/qure/. CONTACT: ahnven@yahoo.it; ahnven@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22088847 TI - Protein subcellular localization of fluorescence imagery using spatial and transform domain features. AB - MOTIVATION: Subcellular localization of proteins is one of the most significant characteristics of living cells. Prediction of protein subcellular locations is crucial to the understanding of various protein functions. Therefore, an accurate, computationally efficient and reliable prediction system is required. RESULTS: In this article, the predictions of various Support Vector Machine (SVM) models have been combined through majority voting. The proposed ensemble SVM SubLoc has achieved the highest success rates of 99.7% using hybrid features of Haralick textures and local binary patterns (HarLBP), 99.4% using hybrid features of Haralick textures and Local Ternary Patterns (HarLTP). In addition, SVM-SubLoc has yielded 99.0% accuracy using only local ternary patterns (LTPs) based features. The dimensionality of HarLBP feature vector is 581 compared with 78 and 52 for HarLTP and LTPs, respectively. Hence, SVM-SubLoc in conjunction with LTPs is fast, sufficiently accurate and simple predictive system. The proposed SVM SubLoc approach thus provides superior prediction performance using the reduced feature space compared with existing approaches. AVAILABILITY: A web server accompanying the proposed prediction scheme is available at http://111.68.99.218/ SVM-SubLoc CONTACT: asif@pieas.edu.pk; khan.asifullah@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22088848 TI - COPD phenotypes: Sueiros's sign. PMID- 22088849 TI - Does load carriage differentially alter postural sway in overweight vs. normal weight schoolchildren? AB - Among a wide range of negative consequences stemming from excess mass in children, recent studies suggest an impairment of postural control, including basic capabilities such as static and dynamic balance. Such impairment may be compounded when additional tasks are performed, such as carrying localized loads as occurs among children using a backpack. To investigate this, postural control was measured among 77 overweight and obese children (6-11 years old), and an equal number of normal-weight children matched for gender, age, and height. Testing was conducted at school, in which center of pressure (COP) time series during quiet standing were obtained in the presence and absence of each student's backpack. A traditional postural control measure derived from COP (mean velocity) did not indicate significant differences between overweight and normal-weight children, regardless of backpack presence. In contrast, a complexity index (derived from multiscale entropy) suggested the existence of different postural strategies and reduced balance capabilities among overweight children, whose consequences need to be further clarified. PMID- 22088850 TI - Between-day reliability of time-to-contact measures used to assess postural stability. AB - Traditional measures of postural stability consider movement of the center of pressure (COP) or the center of mass (COM) without regard to the boundary of support (BOS). A potentially more appropriate measure is postural time-to-contact (TtC) which defines the spatio-temporal proximity of the COM or COP to the BOS. Given the increasing popularity of TtC measures, it is important to determine their reliability. Therefore, the purpose of this study was to determine the effects of the number of trials and trial duration on the reliability of postural TtC measures. COP data were collected (100 Hz) in 16 young healthy participants during 10 trials (60-s duration) of quiet standing with eyes open on two occasions - seven days apart. Postural TtC of each trial was calculated using two different methods. The intersession reliability of the TtC measures was assessed by calculating between session intraclass correlation coefficients (ICC(2,1)) using different combinations of the number of trials (1-10) and trial duration (10, 20, 30, 40, 50 and 60s). Both TtC methods were very reliable. Additionally, both measures of TtC were more reliable than the standard deviation of the anterior-posterior COP and slightly more reliable than path length. This difference was most pronounced when fewer and shorter trials were used. PMID- 22088851 TI - Black-on-clear piggyback technique for a black occlusive intraocular device in intractable diplopia. AB - Black occlusive intraocular devices have been used successfully for intractable binocular diplopia. We describe a novel technique of implanting both a black occlusive device and a clear poly(methyl methacrylate) intraocular lens (IOL) in the capsular bag during phacoemulsification surgery. If the need should arise at a later date, this approach will allow safer and easier explantation of the black occlusive device, avoiding the need for IOL exchange. PMID- 22088852 TI - Walking assessment with instrumented insoles in patients with lower limb spasticity after botulinum toxin infiltration. AB - INTRODUCTION: Botulinum toxin A (BTA) improves the kinematic parameters of gait in patients with spasticity of lower limbs, but there are no studies in which kinetic parameters are measured with instrumented insoles. We therefore used instrumented insoles to perform a functional assessment of therapeutic results in patients with lower limb spasticity after brain injury or spinal cord infiltration indicating BTA. MATERIAL AND METHODS: Ten patients (11 lower limbs) seen in a Neurorehabilitation Unit. The tests carried out included clinical examination, gait assessment (Functional Ambulation Categories (FAC); Hospital de Sagunto Gait Scale), and biomechanical assessment (Biofoot / IBV version 5.0), before and three weeks after infiltration with BTA. STATISTICS: t-test for related samples of clinical variables, functional variables and biomechanical variables before and after infiltration. Level of significance P< .05. Qualitative method to assess whether changes in the biomechanical variables tended toward normal values. RESULTS: BTA improves muscle tone, joint arch and frequency of spasms (P<.01). The patient sample showed a high level of satisfaction with the improvement in symptoms. There were no changes in walking ability after injection. There were no statistically significant changes in biomechanical parameters, but there was improved gait cadence. The relatively small statistical significance close to P=.1 of the peak pressure in the heel after injection indicates the need for further studies with instrumented insoles in people with spasticity due to central nervous system injury. CONCLUSIONS: With the decrease in muscle tone after infiltration with BTA the clinical symptoms associated with muscle tone improved without any functional changes in gait scales. The changes in the biomechanical parameters show that larger studies using instrumented insoles should be performed in the population with spasticity after a central nervous system injury treated with BTA infiltration. PMID- 22088853 TI - Clinical and spatiotemporal gait effects of canes in hip osteoarthritis. AB - OBJECTIVE: To investigate the effects of cane use on spatiotemporal gait parameters, pain, and function in adults with hip osteoarthritis (OA). DESIGN: Prospective observational study. SETTING: An academic tertiary Veterans Affairs Healthcare Center. PARTICIPANTS: Thirteen adults with symptomatic hip OA and 13 healthy adults. METHODS: We undertook gait analysis in all subjects with an optoelectronic camera system. Pain, stiffness, and physical function in subjects with hip OA were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). MAIN OUTCOME MEASUREMENTS: Baseline spatiotemporal measures of unaided gait were obtained for healthy subjects. Baseline and 4-week spatiotemporal gait parameters were assessed for hip OA subjects while they walked with and without a cane. Participants with hip OA completed the WOMAC at baseline and after 4 weeks of cane use. RESULTS: At baseline when walking unaided, the subjects with hip OA (age range 60-75 years) had a significantly slower gait velocity, shorter affected limb stride length, and longer double stance time compared with healthy control subjects. When walking with a cane, they had a reduction in gait velocity (P < .05) caused by a decrease in cadence (P < .05) compared with walking unaided. After 4 weeks of cane use, the participants with hip OA demonstrated significant improvements in gait velocity (P < .05) and double-stance time (P < .05) when walking with a cane in comparison with baseline data. There was no improvement in pain and function after 4 weeks of cane use, a period in which only approximately 60% of the hip OA subjects used the cane 6 or more times per week. CONCLUSIONS: Initial use of a cane led to decreased gait velocity and cadence in people with hip OA compared with walking unaided. This difference in gait velocity diminished after they practiced walking with the cane. Inconsistent use of the cane may have contributed to the lack of improvement in the subjects' hip OA pain and function. PMID- 22088854 TI - An assessment of the compliance and utility of a home exercise DVD for caregivers of children and adolescents with brachial plexus palsy: a pilot study. AB - OBJECTIVE: To investigate the impact of a video-based educational resource on home exercise compliance among caregivers of children with neonatal brachial plexus palsy (NBPP). DESIGN: Retrospective analysis of self-reported caregiver home exercise habits and resultant shoulder range of motion (ROM) and biceps power in patients with NBPP. SETTING: Home-based exercise program. PARTICIPANTS: Adult caregivers of children with NBPP followed up through the Brachial Plexus Program at the University of Michigan (N = 83 surveyed initially, with N = 37 completing the final survey). METHODS: Caregivers completed surveys before and approximately 3, 6, and 12 months (times A, B, and C, respectively) after receiving the "Home Exercise Therapy Program for Brachial Plexus Palsy" digital video disk (DVD). A retrospective analysis of shoulder ROM and biceps power of patients was completed as representative of arm function during the study. MAIN OUTCOME MEASUREMENTS: Surveys assessed home exercise compliance, resources used to guide exercises, and caregiver confidence in the correctness of exercises being performed. Functional outcomes analyzed include biceps strength and shoulder active and passive ROM. RESULTS: Home exercise compliance increased from 74% initially to 96% at time A (P < .001), remained at 94% at time B (P < .001), and fell to 84% at time C (P = .016). Use of the DVD to guide home exercise decreased from 69% at time A to 57% at time B and C (P = .026). After receiving the DVD, exercise frequency and caregiver confidence increased. Although some measures of shoulder active ROM and biceps power improved during the course of the study, there was no consistent statistically significant relationship between increased caregiver confidence and functional outcomes. No causal relationship exists between DVD content and functional status at this time. CONCLUSIONS: As the first formal evaluation of a video-based resource guiding exercise therapy for children with NBPP, we suggest that this population may be receptive to alternative media and may benefit from dynamic modeling of home exercises. PMID- 22088855 TI - The dimensionality and measurement properties of alcohol outcome expectancies across Hispanic national groups. AB - This study examines the psychometric properties of alcohol expectancies among Hispanic subgroups. Face-to-face interviews were conducted as part of the 2006 Hispanic Americans Baseline Alcohol Survey (HABLAS), which employed a multistage cluster sample design. A total of 5224 individuals (18+ years of age) representing four Hispanic national groups (Puerto Ricans, Cuban Americans, Mexican Americans, and South/Central Americans) were selected at random from the household population in five metropolitan areas (Miami, New York, Philadelphia, Houston, and Los Angeles). Alcohol expectancies included 18 items covering positive (e.g., laugh more, become more talkative) and negative dimensions (e.g., become aggressive, lose control) when alcohol is consumed. Confirmatory factor models replicated a previously proposed three-factor dimensional structure with a substantial majority of items exhibiting measurement invariance across Hispanic national group and gender. Items covering social extroversion were an exception, showing a lack of invariance for female Cuban and South/Central Americans. Latent mean differences across groups were detected for expectancies concerning emotional fluidity, and the pattern of differences largely mirrored known differences in alcohol consumption patterns. Results suggest that caution should be exercised in interpreting differences in expectancies concerning social extroversion across Hispanic groups, and additional work is needed to identify indices of this construct with invariant measurement properties. However, measures of emotional/behavioral impairment and emotional fluidity expectancies can be validly compared across gender and Hispanic national groups. PMID- 22088856 TI - Parental relationship satisfaction in French young adults associated with alcohol abuse and dependence. AB - Alcohol consumption is a major risk factor for disease in developed countries. In addition to genetic susceptibility, alcohol consumption is shaped by one's social and family environment. With data from 2009, we examined associations between satisfaction with familial relationships and alcohol abuse and dependence using a national sample of 1101 French young adults aged 22-35. Alcohol-related problems were measured with the Alcohol Use Disorders Identification Test (AUDIT). Main exposure variables included young adults' self-report of satisfaction with parental relationships. In adjusted logistic regression models, having a poor relationship with one's mother (OR=1.8, 95%CI 1.0-3.6) or father (OR=1.8, 95% CI 1.0-3.2) was associated with alcohol abuse and dependence. Gender stratified analyses indicated unsatisfactory maternal relationships were associated with alcohol problems in women (OR=2.6, 95%CI 1.1-6.6); unsatisfactory paternal relationships were suggestive of alcohol abuse in men (OR=2.0, 95%CI 0.9-4.7), but not in women. Non-cohabitation with a romantic partner was associated with an almost three-fold increase of alcohol abuse and dependence in men (OR=2.8, 95% CI 1.6-4.8). The quality of parental relationships may be important for alcohol abuse, particularly when the parent is the same gender. Family-centered approaches may be considered in prevention efforts to reduce problem drinking in French young adults. PMID- 22088857 TI - Increased neopterin levels and its association with angiographic variables in patients with slow coronary flow: an observational study. AB - OBJECTIVE: Although various inflammatory markers have been studied in patients with slow coronary flow (SCF), serum neopterin levels have not been studied previously. We investigated the serum neopterin and high sensitivity C-reactive protein (hs-CRP) levels and the relationship between neopterin and hs-CRP levels and TIMI flow in patients with SCF. METHODS: The study group consisted of 51 patients with SCF. An age and gender matched control group was composed of 40 subjects. Coronary flow rates of all patients and control subjects were documented by Thrombolysis in Myocardial Infarction (TIMI) frame count. We measured serum neopterin and hs-CRP levels at the same time in patients with SCF and control subjects in this cross-sectional observational study. Chi-square, Mann-Whitney U and unpaired t tests, Pearson correlation and linear regression analyses were used for statistical analysis. RESULTS: The TIMI frame counts for all coronary arteries and the mean TIMI frame count were significantly higher in the SCF group than controls. Serum neopterin levels were significantly higher among patients with SCF when compared with control group (2.13+/-1.03 vs. 1.60+/ 0.50 ng/ml; p=0.004). Serum hs-CRP levels were significantly higher among patients with SCF when compared with control group (2.06+/-1.32 vs. 0.74+/-0.40 mg/L respectively; p<0.001). There was a significant association of serum neopterin levels (beta=0.60, 95% CI: 4.93-9.06, p<0.001) and serum hs-CRP levels (beta=0.29, 95%CI: 0.84-4.33, p=0.004) with mean TIMI frame count independent of potential confounders such as age, gender, body mass index, smoking, glucose and cholesterol levels. CONCLUSION: We have shown that serum neopterin and hs-CRP levels were significantly elevated in patients with SCF when compared with control subjects. Serum neopterin and hs-CRP levels were correlated with mean TIMI frame count in patients with SCF. PMID- 22088858 TI - [Effects of different statins, ezetimibe/simvastatin combination on hsCRP levels in unstable angina pectoris and non-ST elevation myocardial infarction patients: a randomized trial]. AB - OBJECTIVE: The aim of our study was to evaluate the effects of two different statins and a statin/ezetimibe combination on high sensitive C-reactive protein (hsCRP) values, which were given at high doses in the early period of acute coronary syndromes. METHODS: A total of 150 patients with non-ST elevation myocardial infarction and unstable angina pectoris were enrolled to our prospective, randomized, single-blind study. Patients were divided into three groups by block randomization method. One group received 20 mg/day atorvastatin, one group received 10 mg/day rosuvastatin and the other group received 10 mg/day ezetimibe/simvastatin combination therapy, which was initiated within the first 24 hours of admission. Follow-up duration was 2 months . Biochemical investigations and hsCRP levels (by nephelometric method) were performed with 138 patients evaluated at baseline, 10th and 60th days of therapy. Decreases of hsCRP levels were analyzed with one-way MANOVA and repeated measures of ANOVA methods. Post-hoc Tukey HSD test was performed for finding the different group, when the difference was detected between the groups. RESULTS: Tenth day hsCRP levels in ezetimibe/simvastatin group was significantly lower than the other groups (p<0.001). Further, after 60 days of follow-up a significant reduction was seen in hsCRP levels in ezetimib/simvastatin group (in ezetimibe/simvastatin group the mean hsCRP was reduced from 38.4+/-15.0 mg/L to 2.4+/-1.3 mg/L, in atorvastatin group the mean hsCRP was reduced from 27.3+/-11.7 mg/L to 4.1+/-2.4 mg/L and in rosuvastatin group the mean hsCRP was reduced from 22.0+/-6.9 mg/L to 3.6+/-1.7 mg/L (F (1.1, 148.2) = 746.9, p<0.01 and the difference between drugs; F (2.2, 148.2) = 32.1, p<0.01). No side effects related to drugs were seen during follow up in all three treatment groups. CONCLUSION: This study showed that ezetimibe/simvastatin 10 mg/day combination treatment was superior to atorvastatin 20 mg/day and rosuvastatin 10 mg/day treatment in reducing the inflammatory markers when high dose statins was started in the early period of unstable angina and non ST elevation myocardial infarction. PMID- 22088859 TI - Novel method to evaluate the conduction velocity and conducting area during isthmus-dependent atrial flutter. AB - OBJECTIVE: The difference of the conduction velocity (CV) around the tricuspid valve annulus between the counter-clockwise (CCW) atrial flutter and the clockwise (CW) atrial flutter has not been well clarified. This study was undertaken to evaluate the CV and the conducting area (CA) per millisecond around the tricuspid valve annulus using the electroanatomical mapping. METHODS: The electroanatomical mapping was performed during the tachycardia for 30 consecutive patients (mean age: 61+/-16 years) with isthmus-dependent atrial flutter (CCW, 25; CW, 5). We measured the CV and the CA of five divided areas of the right atrium, that is, upper septum (US), lower septum (LS), isthmus (I), upper lateral wall (UL) and lower lateral wall (LL) using the novel measurement method in the isochronal map. Statistical differences of these data between the two groups were assessed by the Student's t-test and one-way analysis of variance methods. RESULTS: In total, the CV of the LS was significantly slower than other areas (m/sec: US, 0.57+/-0.18; LS, 0.43+/-0.18; UL, 0.60+/-0.26; LL, 0.53+/-0.20; I, 0.50+/-0.17; p<0.05) and the CA of the US and UL were significantly larger than other areas (mm2/sec: US, 34.5+/-16.2; LS, 16.2+/-9.5; UL, 40.0+/-14.1; LL, 27.0+/-17.0; I, 16.8+/-8.5; p<0.0001). There was no significant difference between the CCW and the CW atrial flutters in terms of the CV and the CA of equally divided five areas. CONCLUSION: In both of the CCW and the CW atrial flutters, the CV of the LS was significantly slower than other areas and the CA of the lower atrium was significantly smaller than the upper atrium. PMID- 22088860 TI - [Comparison of left and right ventricular pulsed and tissue Doppler myocardial performance index values using Z-score in newborns with hypoxic-ischemic encephalopathy]. AB - OBJECTIVE: The aim of the study is determination of myocardial performance index (MPI/Tei index) using pulsed (PD) and tissue Doppler (TD) techniques to show cardiac response in newborns with hypoxic-ischemic encephalopathy (HIE) and healthy newborns and eventually evaluation of the differences between these two techniques. METHODS: The study is a prospective observational study. Twenty term newborns diagnosed as perinatal asphyxia during postnatal 24 hours due to the defined criteria and fifty healthy term neonates as control group were included the study. Hypoxic group was divided into two groups with Sarnat stages, Sarnat Stage 1 and 2-3. MPIs (Tei indexes) were calculated with PD and TD echocardiographic techniques in all groups after the 24 hours of birth and one year later. The statistical differences between same techniques were calculated with Kruskal-Wallis test and Z score was used to compare the superiority of two techniques. RESULTS: The MPI values calculated by PD (0.41+/-0.04, 0.51+/-0.02) and TD (0.59+/-0.04, 0.51+/-0.02) during the first day of life in Sarnat Stage 2 3 in both ventricles were significantly higher than the control group (p<0.01, p<0.02, p<0.03). While the Z score, calculated for MPI measured by PD and TD methods, were found similar in both ventricles in Sarnat Stage 1 and control groups, it was significantly different in other groups of Sarnat stages. CONCLUSION: The degree of cardiac response in neonates with HIE is associated with the severity of hypoxia. MPI values are not different from the controls in newborns received mild hypoxia while they are higher in the patients who were received moderate or severe hypoxia. Any advantage could not be found between two techniques according to the measurement values, but higher variability in the value of MPI, measured by TD method, calculated from moderate and severe hypoxia group was detected. PMID- 22088861 TI - [Follow-up of our patients with transposition of the great arteries and arterial switch operation; comparison of simple and complex transposition cases]. AB - OBJECTIVE: 1. Follow-up data of patients with simple transposition of great arteries (TGA) and TGA with ventricular septal defect (VSD), who had arterial switch operation (ASO) are compared. 2. Factors affecting mortality and morbidity after ASO are described. METHODS: Seventy-six patients, who had an ASO between April 2007 and August 2010 were studied retrospectively. The patients with intact ventricular septum (IVS) (n=36) were in Group 1, and those with VSD (n=40) in Group 2. The pre and postoperative clinical and echocardiographic variables and intensive care unit (ICU) outcomes were compared among groups using Mann-Whitney U, Pearson correlation and logistic regression tests. RESULTS: The mean age at operation was 44.1 days, weight was 3.6+/-0.98 kg. Patients were followed for 15.5+/-11.21 months. The aortic cross-clamp (AoCC) and cardiopulmonary bypass (CPB) times were higher in patients with VSD (p=0.001, p=0.004). Patients in Group 1 had longer inotropic agent infusion (p=0.001). Length of stay in ICU was similar in two groups (p>0.05). There was no correlation between the length of stay in ICU and age, weight, CPB time, AoCC time. Aortic regurgitation was more frequent in Group 2 (p=0.02). During follow-up, 12 patients died (15.7%), and 8 patients had a revision operation (10.5%) (diaphragmatic plication in 4, pulmonary artery reconstruction in 1, recoarctation operation in 3 patients). Mortality was similar in groups (p>0.05). CONCLUSION: Arterial switch operation provides anatomical correction in TGA. Appropriate timing and good perioperative planning facilitates low morbidity and mortality in patients with VSD as in patients with simple TGA. PMID- 22088862 TI - Seroprevalence of dengue infection: a cross-sectional survey in mainland Tanzania and on Pemba Island, Zanzibar. AB - OBJECTIVE: Evidence available to date indicates that dengue viruses 1, 2, and 3 could be among the causes of acute fever in eastern Africa. Recently, four reports on dengue infection in travelers and residents have raised concerns over the occurrence of dengue fever in mainland Tanzania and in Zanzibar. The objective of this study was to provide seroprevalence data on dengue infection in Tanzania. METHODS: This study was conducted in 2007 at two peripheral hospitals, one on Pemba Island, Zanzibar and one in Tosamaganga, Iringa Region, mainland Tanzania. Two hundred and two consecutive febrile outpatients were studied for antibodies and viral RNA to assess the circulation of dengue virus in Tanzania. RESULTS: A seroprevalence of 7.7% was found on Pemba Island and of 1.8% was found in Tosamaganga. No acute cases and no previous infections among patients under 11 years of age were detected. CONCLUSION: These findings provide the first baseline data on dengue seroprevalence in the country. No recent dengue virus circulation in Tanzania and in the Zanzibar archipelago up until the early 1990s is reported. PMID- 22088863 TI - Comparative evaluation of intratracheal colistimethate sodium, imipenem, and meropenem in BALB/c mice with carbapenem-resistant Acinetobacter baumannii pneumonia. AB - OBJECTIVE: The identification of the optimal agent for administration via the respiratory tract when treating pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: A murine model of acute CRAB pneumonia was established by intratracheal (i.t.) inoculation with 2.5 * 107 colony-forming units (CFU) of A. baumannii strain Ab396 plus 10% porcine mucin. After 4h the infected BALB/c mice were treated intratracheally with 25MUl of either 0.85% saline (control group), colistimethate sodium (CMS) (166 666 U/kg, CMS group), imipenem/cilastatin (30/30 mg/kg, imipenem group), or meropenem (20mg/kg, meropenem group), every 8h. The therapeutic efficacy of these agents was examined. RESULTS: A. baumannii strain Ab396 was susceptible to CMS only. However, meropenem treatment did give a significantly superior survival rate (100%) compared to treatment with imipenem (50%), CMS (33%), or saline (0%) (p<0.001 vs. the control and CMS groups, p=0.006 vs. the imipenem group, by log rank test). Furthermore, compared to the other groups, the meropenem group demonstrated significantly more favorable results in terms of tissue penetration of the antibiotic, bacterial clearance, normalization of the wet lung-to-body weight ratio, and down-regulation of pro-inflammatory cytokine levels in the lungs. CONCLUSIONS: Administration of meropenem via the respiratory tract proved to have the best therapeutic efficacy among the antibiotics tested when treating advanced murine CRAB pneumonia. PMID- 22088864 TI - Biological effects of the anti-parasitic chemotherapeutant emamectin benzoate on a non-target crustacean, the spot prawn (Pandalus platyceros Brandt, 1851) under laboratory conditions. AB - The potential impact of commercial salmon aquaculture along the coast of British Columbia on the health of non-target marine wildlife is of growing concern. In the current initiative, the biological effects on gene expression within spot prawn (Pandalus platyceros) exposed to the sea lice controlling agent, emamectin benzoate (EB; 0.1-4.8 mg/kg sediment), were investigated. A mean sediment/water partitioning coefficient (K(p)) was determined to be 21.81 and significant levels of EB were detected in the tail muscle tissue in all exposed animals. Animals selected for the experiment did not have eggs and were of similar weight. Significant mortality was observed within 8 days of EB treatment at concentrations between 0.1 and 0.8 mg/kg and there was no effect of EB on molting. Twelve spot prawn cDNA sequences were isolated from the tail muscle either by directed cloning or subtractive hybridization of control versus EB exposed tissues. Three of the transcripts most affected by EB exposure matched sequences encoding the 60S ribosomal protein L22, spliceosome RNA helicase WM6/UAP56, and the intracellular signal mediator histidine triad nucleotide binding protein 1 suggesting that translation, transcription regulation, and apoptosis pathways were impacted. The mRNA encoding the molting enzyme, beta-N acetylglucosaminidase, was not affected by EB treatment. However, the expression of this transcript was extremely variable making it unsuitable for effects assessment. The results suggest that short-term exposure to EB can impact biological processes within this non-target crustacean. PMID- 22088865 TI - Generalized rough fuzzy c-means algorithm for brain MR image segmentation. AB - Fuzzy sets and rough sets have been widely used in many clustering algorithms for medical image segmentation, and have recently been combined together to better deal with the uncertainty implied in observed image data. Despite of their wide spread applications, traditional hybrid approaches are sensitive to the empirical weighting parameters and random initialization, and hence may produce less accurate results. In this paper, a novel hybrid clustering approach, namely the generalized rough fuzzy c-means (GRFCM) algorithm is proposed for brain MR image segmentation. In this algorithm, each cluster is characterized by three automatically determined rough-fuzzy regions, and accordingly the membership of each pixel is estimated with respect to the region it locates. The importance of each region is balanced by a weighting parameter, and the bias field in MR images is modeled by a linear combination of orthogonal polynomials. The weighting parameter estimation and bias field correction have been incorporated into the iterative clustering process. Our algorithm has been compared to the existing rough c-means and hybrid clustering algorithms in both synthetic and clinical brain MR images. Experimental results demonstrate that the proposed algorithm is more robust to the initialization, noise, and bias field, and can produce more accurate and reliable segmentations. PMID- 22088866 TI - A prescription fraud detection model. AB - Prescription fraud is a main problem that causes substantial monetary loss in health care systems. We aimed to develop a model for detecting cases of prescription fraud and test it on real world data from a large multi-center medical prescription database. Conventionally, prescription fraud detection is conducted on random samples by human experts. However, the samples might be misleading and manual detection is costly. We propose a novel distance based on data-mining approach for assessing the fraudulent risk of prescriptions regarding cross-features. Final tests have been conducted on adult cardiac surgery database. The results obtained from experiments reveal that the proposed model works considerably well with a true positive rate of 77.4% and a false positive rate of 6% for the fraudulent medical prescriptions. The proposed model has the potential advantages including on-line risk prediction for prescription fraud, off-line analysis of high-risk prescriptions by human experts, and self-learning ability by regular updates of the integrative data sets. We conclude that incorporating such a system in health authorities, social security agencies and insurance companies would improve efficiency of internal review to ensure compliance with the law, and radically decrease human-expert auditing costs. PMID- 22088867 TI - Improving the medical scale predictability by the pairwise comparisons method: evidence from a clinical data study. AB - In the clinical practice of psychiatry, presence or absence of particular symptoms is based on the subjective interpretation, by the clinician, of mental and behavioural descriptions offered by the patient. However, this subjectivity that characterizes the diagnostic decision making process may limit the reliability of diagnosis. In this current study, the pairwise comparisons (PC) method is used to investigate whether the psychometric properties of a medical screening questionnaire can be improved. The pilot data described herein did indeed demonstrate that modest improvements in diagnostic accuracy could be achieved using PC, and provides early evidence that the inconsistency produced by subjective clinical ratings can be reduced using this method, thus providing impetus for further investigation. PMID- 22088868 TI - Sperm ultrastructure of the digenean Aphallus tubarium (Rudolphi, 1819) Poche, 1926 (Platyhelminthes, Cryptogonimidae) intestinal parasite of Dentex dentex (Pisces, Teleostei). AB - The ultrastructural organization of the spermatozoon of a cryptogonimid digenean, Aphallus tubarium, a parasite of Dentex dentex, is described. The spermatozoon possesses the elements found in other digeneans: two axonemes with 9+"1" pattern, a mitochondrion, a nucleus, cortical microtubules, external ornamentation and spine-like bodies. However, the mitochondrion appears as a cord with a bulge; this characteristic has never been described in other studied cryptogonimid and in other digeneans except in one lepocreadiid, Holorchis micracanthum. Likewise, the presence of a thin cytoplasm termination in the anterior part of the spermatozoon has never been pointed out in the cryptogonimids. PMID- 22088869 TI - Genetics and patient outcome after cardiac surgery: unravelling translational findings. PMID- 22088870 TI - Is it time to implement preoperative platelet function testing before invasive procedures? PMID- 22088871 TI - Genetic interactions in the beta-adrenoceptor/G-protein signal transduction pathway and survival after coronary artery bypass grafting: a pilot study. AB - BACKGROUND: In heart failure, beta-adrenergic receptor (betaAR) stimulation desensitizes the receptor, uncouples the downstream Galphas protein, and diminishes signal transduction. We tested the hypotheses that haplotype-tagging single-nucleotide polymorphisms (htSNPs) within the Galphas gene (GNAS) (i) are functionally active and alter Galphas expression, (ii) influence survival after coronary artery bypass grafting (CABG), and (iii) interact with betaAR SNPs. METHODS: Amplification of GNAS intron 1 was followed by cloning, reporter assays, electrophoretic mobility shift assays, and western blots. In a pilot study, 185 patients on betaAR blockade undergoing CABG were studied prospectively. The primary endpoint was cardiac-related mortality at 1 yr. RESULTS: Two htSNPs defined three common haplotypes with altered reporter activity, allele-specific transcription factor binding, and Galphas protein expression (highest in *3 carriers followed by *2 and *1 haplotypes, P=0.013). After CABG, mortality was GNAS diplotype-dependent: *3/*3: 0%; *3/*2: 2.4%; *3/*1: 2.9%; *2/*2: 4.5%; *2/*1: 9.1%; and *1/*1: 20.0% (P=0.004). While beta(1)AR SNPs were not associated with mortality, beta(2)AR Arg16 allele carriers were at higher risk than Gly16 allele carriers (P=0.008). Gene-gene interaction using gene-related risk alleles demonstrated the number of risk alleles to be independently associated with death (hazard ratio 2.3; 95% confidence interval: 1.5-3.5; P=0.0003). Carriers of the no-risk allele had higher maximum isoproterenol-stimulated adenylyl cyclase activities than risk allele carriers (P=0.003). CONCLUSIONS: Interactions in the betaAR/Galphas pathway may be associated with altered mortality after CABG. This could reconcile previously inconclusive data regarding the effects of betaAR SNPs on cardiovascular prognosis. PMID- 22088872 TI - Prophylactic magnesium sulphate and postoperative supraventricular arrhythmias in patients undergoing thoracotomy. Letter 2. PMID- 22088873 TI - Prophylactic magnesium sulphate and postoperative supraventricular arrhythmias in patients undergoing thoracotomy. Letter 1. PMID- 22088875 TI - Does hyperbaric oxygen have positive effect on neurological recovery in spinal epidural haematoma? A case report. PMID- 22088876 TI - Combined ultrasound imaging and hydrolocalization technique for accurate placement of perineural catheters. PMID- 22088877 TI - Prone ventilation for refractory hypoxaemia in a patient with severe chest wall disruption and traumatic brain injury. PMID- 22088878 TI - Acute severe hypoxaemia after mechanical ventilation in a patient with an Ebstein anomaly requiring extracorporeal membrane oxygenation. PMID- 22088879 TI - Fluid optimization guided by oesophageal Doppler significantly improves bowel perfusion. PMID- 22088880 TI - A survey of patients discharged to the community on modified-release strong opioids by a tertiary level acute pain service. PMID- 22088881 TI - Use of two oxygenators during extracorporeal membrane oxygenator for a patient with acute respiratory distress syndrome, high-pressure ventilation, hypercapnia, and traumatic brain injury. PMID- 22088883 TI - Chiral pool synthesis of calystegine A3 from 2-deoxyglucose via a Brown allylation. AB - Calystegine A(3) is a naturally occurring nortropane iminosugar of which there previously have been three total syntheses. Inspired by our previous work we here report on a fourth approach using 17 steps from 2-deoxy-d-glucose applying a diastereoselective allylation protocol. PMID- 22088884 TI - A new approach for the N- and S-galactosylation of 5-arylidene-2-thioxo-4 thiazolidinones. AB - N- and S-galactosylation was carried out via the reaction of 5-((Z)-arylidene)-2 thioxo-4-thiazolidinones with 2,3,4,6-tetra-O-acetyl-alpha-d-galactopyranosyl bromide under alkaline conditions or under silylation conditions. Deacetylation of the N-galactosylation products was performed with concentrated hydrochloric acid in methanol (3.5%) or sodium methoxide in methanol without cleavage of the 2 thioxo-4-thaizolidinone ring by means of acid hydrolysis. The anomers were separated by flash column chromatography, and their configurations were assigned by NMR spectroscopy. The deprotected nucleosides were screened against leukemia L 1210 and were found inactive. PMID- 22088885 TI - A reevaluation of the epimeric and anomeric relationship of glucosides and galactosides in thermotropic liquid crystal self-assemblies. AB - Anomers and epimers alpha- and beta-gluco and -galactosides are expected to behave differently. However, recent results on a series of Guerbet glycosides have indicated similar liquid crystal clearing temperatures for pure beta glucosides and the corresponding alpha-galactosides. This observation has led to speculation on similarities in the self-assembly interactions between the two systems, attributed to the trans-configuration of the 4-OH group and the hydrophobic aglycon. Previous simulations on related bilayers systems support this hypothesis, by relating this clearing transition temperature to intralayer (sugar-sugar) hydrogen bonding. In order to confirm the hypothesis, the comparison was expanded to include the cis-configurated pair, that is, alpha gluco/beta-galactoside. A set of alpha-configurated Guerbet glucosides as well as octyl alpha-galactoside were prepared and their thermotropic phase behavior studied. The data obtained enabled a complete comparison of the isomers of interest. While the results in general are in line with a pairing of the stereo isomers according to the indicated cis/trans-configuration, differences within the pairs can be explained based on the direction of hydrogen bonds from a simple modeling study. PMID- 22088886 TI - Are male neonates more vulnerable to neonatal abstinence syndrome than female neonates? AB - BACKGROUND: Prior studies have shown an increased vulnerability among males to adverse outcomes during the postnatal period. Most children exposed to opioids and other medications in utero develop neonatal abstinence syndrome (NAS), yet individual predisposition for NAS is poorly understood. OBJECTIVE: This investigation examined the role of neonatal sex in the postnatal period for neonates exposed to standardized opioid maintenance treatment in utero with a focus on NAS regarding severity, medication requirements, and duration. METHODS: This was a secondary analysis of data collected in a prospective randomized, double-blind, double-dummy, multicenter trial (MOTHER study) that examined the comparative safety and efficacy of methadone and buprenorphine during pregnancy. A total of 131 neonates born to opioid-dependent women randomized at 6 US sites (n = 74) and 1 European site (n = 37) were analyzed. Sex-based differences in birth weight, length, head circumference, NAS duration, NAS severity, and treatment parameters of full-term neonates were assessed. RESULTS: Males had a significantly higher birth weight (P = 0.027) and head circumference (P = 0.017) compared with females, with no significant sex difference in rates of preterm delivery. No significant sex-related differences were found for NAS development, severity, or duration, or medication administered, and there were no significant differences in concomitant drug consumption during pregnancy (P = 0.959). CONCLUSIONS: This unique prospective study shows similar postnatal vulnerability for both sexes, suggesting that factors other than sex are the major determinants of clinically significant NAS. ClinicalTrials.gov identifier: NCT 00271219. PMID- 22088889 TI - Dental follicle cells and treated dentin matrix scaffold for tissue engineering the tooth root. AB - Tissue engineering strategies to reconstruct tooth roots are an effective therapy for the treatment of tooth loss. However, strategies to successfully regenerate tooth roots have not been developed and optimized. In the present study, rat dental follicle stem cells (DFCs) were characterized, followed by a thorough investigation of tooth roots regeneration for a combination of DFCs seeding cells, treated dentin matrix (TDM) scaffolds, and an inductive alveolar fossa microenvironment. Eighteen clones derived from single DFCs were harvested; however, only three clones were amplified successfully more than five passages and 90-95 days in culture. Following 270 days or 30 passages, the heterogeneous DFCs showed suitable characteristics for seeding cells to regenerate tooth roots. However, various features, such as variable proliferation rates, differentiation characteristics, apoptosis rates, and total lifespan were observed in DFCs and the three clones. Importantly, upon transplantation of DFCs combined with TDM for four weeks, root-like tissues stained positive for markers of dental pulp and periodontal tissues were regenerated in the alveolar fossa, but not in the skull and omental pockets. These results indicate that tooth roots were successfully regenerated and suggest that the combination of DFCs with TDM in the alveolar fossa is a feasible strategy for tooth roots regeneration. This strategy could be a promising approach for the treatment of clinical tooth loss and provides a perspective with potential applications to regeneration of other tissues and organs. PMID- 22088888 TI - Protein adsorption in three dimensions. AB - Recent experimental and theoretical work clarifying the physical chemistry of blood-protein adsorption from aqueous-buffer solution to various kinds of surfaces is reviewed and interpreted within the context of biomaterial applications, especially toward development of cardiovascular biomaterials. The importance of this subject in biomaterials surface science is emphasized by reducing the "protein-adsorption problem" to three core questions that require quantitative answer. An overview of the protein-adsorption literature identifies some of the sources of inconsistency among many investigators participating in more than five decades of focused research. A tutorial on the fundamental biophysical chemistry of protein adsorption sets the stage for a detailed discussion of the kinetics and thermodynamics of protein adsorption, including adsorption competition between two proteins for the same adsorbent immersed in a binary-protein mixture. Both kinetics and steady-state adsorption can be rationalized using a single interpretive paradigm asserting that protein molecules partition from solution into a three-dimensional (3D) interphase separating bulk solution from the physical-adsorbent surface. Adsorbed protein collects in one-or-more adsorbed layers, depending on protein size, solution concentration, and adsorbent surface energy (water wettability). The adsorption process begins with the hydration of an adsorbent surface brought into contact with an aqueous-protein solution. Surface hydration reactions instantaneously form a thin, pseudo-2D interface between the adsorbent and protein solution. Protein molecules rapidly diffuse into this newly formed interface, creating a truly 3D interphase that inflates with arriving proteins and fills to capacity within milliseconds at mg/mL bulk-solution concentrations C(B). This inflated interphase subsequently undergoes time-dependent (minutes-to-hours) decrease in volume V(I) by expulsion of either-or-both interphase water and initially adsorbed protein. Interphase protein concentration C(I) increases as V(I) decreases, resulting in slow reduction in interfacial energetics. Steady state is governed by a net partition coefficient P=(C(I)/C(B)). In the process of occupying space within the interphase, adsorbing protein molecules must displace an equivalent volume of interphase water. Interphase water is itself associated with surface-bound water through a network of transient hydrogen bonds. Displacement of interphase water thus requires an amount of energy that depends on the adsorbent surface chemistry/energy. This "adsorption-dehydration" step is the significant free energy cost of adsorption that controls the maximum amount of protein that can be adsorbed at steady state to a unit adsorbent surface area (the adsorbent capacity). As adsorbent hydrophilicity increases, adsorbent capacity monotonically decreases because the energetic cost of surface dehydration increases, ultimately leading to no protein adsorption near an adsorbent water wettability (surface energy) characterized by a water contact angle theta->65( degrees ). Consequently, protein does not adsorb (accumulate at interphase concentrations greater than bulk solution) to more hydrophilic adsorbents exhibiting theta<65( degrees ). For adsorbents bearing strong Lewis acid/base chemistry such as ion-exchange resins, protein/surface interactions can be highly favorable, causing protein to adsorb in multilayers in a relatively thick interphase. A straightforward, three-component free energy relationship captures salient features of protein adsorption to all surfaces predicting that the overall free energy of protein adsorption DeltaG(ads)(o) is a relatively small multiple of thermal energy for any surface chemistry (except perhaps for bioengineered surfaces bearing specific ligands for adsorbing protein) because a surface chemistry that interacts chemically with proteins must also interact with water through hydrogen bonding. In this way, water moderates protein adsorption to any surface by competing with adsorbing protein molecules. This Leading Opinion ends by proposing several changes to the protein-adsorption paradigm that might advance answers to the three core questions that frame the "protein adsorption problem" that is so fundamental to biomaterials surface science. PMID- 22088890 TI - Death in pain: peripheral nerve injury and spinal neurodegenerative mechanisms. AB - A complex network operates in the spinal dorsal horn to integrate peripheral nociceptive inputs with local and descending control mechanisms, and to cross talk with higher brain areas. Injury to peripheral sensory nerves can trigger a cascade of events within this relay which, in some cases, may turn into abnormal responses outlasting the initial detrimental stimulus and leading to chronic pain. In the spinal dorsal horn, evidence has been provided both in support and against the occurrence of neuronal loss following peripheral nerve injury, leaving this issue still unresolved. Only new conceptual and technical approaches will determine the relevance of spinal neurodegenerative mechanisms to chronic pain states and allow translation into novel therapeutic targets. PMID- 22088887 TI - Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases. AB - Recent advances in the development and discovery of pharmacological interventions within the ubiquitin-proteasome system (UPS) have uncovered an enormous potential for possible novel treatments of neurodegenerative disease, cancer, immunological disorder and microbial infection. Interference with proteasome activity, although initially considered unlikely to be exploitable clinically, has already proved to be very effective against haematological malignancies, and more specific derivatives that target subsets of proteasomes are emerging. Recent small molecule screens have revealed inhibitors against ubiquitin-conjugating and deconjugating enzymes, many of which have been evaluated for their potential use as therapeutics, either as single agents or in synergy with other drugs. Here, we discuss recent advances in the characterisation of novel UPS modulators (in particular, inhibitors of ubiquitin-conjugating and -deconjugating enzymes) and how they pave the way towards new therapeutic approaches for the treatment of proteotoxic disease, cancer and microbial infection. PMID- 22088891 TI - A celebration of Steven Gabbe's contributions and accomplishments: Associate Editor, American Journal of Obstetrics and Gynecology, 1990 through 2010. PMID- 22088893 TI - Bloody mess. PMID- 22088894 TI - Bloody tests. PMID- 22088897 TI - Attitudes of women in their forties toward the 2009 USPSTF mammogram guidelines: a randomized trial on the effects of media exposure. AB - OBJECTIVE: The objective of the study was to assess women's attitudes toward 2009 US Preventive Services Task Force mammography screening guideline changes and evaluate the role of media in shaping opinions. STUDY DESIGN: Two hundred forty nine women, aged 39-49 years, presenting for annual examinations randomized to read 1 of 2 articles, and survey completion comprised the design of the study. RESULTS: Eighty-eight percent overestimated the lifetime breast cancer (BrCa) risk. Eighty-nine percent want yearly mammograms in their 40s. Eighty-six percent felt the changes were unsafe, and even if the changes were doctor recommended, 84% would not delay screening until age 50 years. Those with a friend/relative with BrCa were more likely to want annual mammography in their forties (92% vs 77%, P = .001), and feel changes unsafe (91% vs 69%, P <= .0001). Participants with previous false-positive mammograms were less likely to accept doctor recommended screening delay until age 50 years (8% vs 21%, P = .01). CONCLUSION: Women overestimate BrCa risk. Skepticism of new mammogram guidelines exists, and is increased by exposure to negative media. Those with prior false-positive mammograms are less likely to accept changes. PMID- 22088898 TI - Perioperative complications of history-indicated and ultrasound-indicated cervical cerclage. AB - OBJECTIVE: To evaluate perioperative complications of history- and ultrasound indicated cerclage. METHODS: We performed a retrospective observational study of a cohort of patients who underwent history- (n = 198) or ultrasound-indicated (n = 89) cerclage procedures. We evaluated the rates of perioperative complications based on indication for cerclage. The chi(2) was used for categorical variables and Student t test for continuous data. RESULTS: One patient (0.35%) had an intraoperative complication (unsuccessful regional anesthesia) and 1 patient (0.35%) had a postoperative complication (contractions and bleeding 2 weeks after cerclage placement, delivered a nonviable infant). Peripartum complications included chorioamnionitis (6.2%), preterm premature rupture of membranes (11%), preterm delivery (20%), and delivery before 32 weeks' gestational age (8%), and they were similar in the history-indicated and ultrasound-indicated groups. CONCLUSION: History- and ultrasound-indicated cerclages are associated with a 0.6%; 95% confidence interval, -0.26 to 1.66 risk of perioperative complications. There was no difference in perioperative complications or outcome between the 2 groups. PMID- 22088899 TI - Cervical collagen concentration within 15 months after delivery. AB - OBJECTIVE: Cervical collagen concentration decreases during pregnancy. The increased risk of preterm birth after a short interpregnancy interval may be explained by an incomplete remodeling of the cervix. The objective of this study was to describe the changes in cervical collagen concentration over 15 months after delivery. STUDY DESIGN: The collagen concentrations were determined in cervical biopsy specimens that were obtained from 15 women at 3, 6, 9, 12, and 15 months after delivery. RESULTS: The mean cervical collagen concentrations were 50%, 59%, 63%, 65%, and 65% of dry weight (SD, 4.2-6.5). This increase was statistically significant until month 9, but not between months 9 and 12. CONCLUSION: Low collagen concentrations in the uterine cervix may contribute to the association between a short interpregnancy interval and preterm birth. PMID- 22088900 TI - Discussion: 'Predictors of massive blood loss from placenta accreta' by Wright et al. PMID- 22088901 TI - Microbial adhesins to gastrointestinal mucus. AB - The gastrointestinal tract (GIT) is lined by a layer of mucus formed by mucin glycoproteins. This layer constitutes a physical and chemical barrier between the intestinal contents and the underlying epithelia. In addition to this protective role, mucins harbor glycan-rich domains that provide preferential binding sites for pathogens and commensal bacteria. Although mucus-microbial interactions in the GIT play a crucial role in determining the outcome of relationships of both commensal and pathogens with the host, the adhesins and ligands involved in the interaction are poorly delineated. This review focuses on the current knowledge of microbial adhesins to gastrointestinal mucus and mucus components. PMID- 22088903 TI - Integrated models of care delivery for the frail elderly: international perspectives. AB - INTRODUCTION: Interest is growing in integrated systems of care for the frail elderly. Few such systems have been both documented and evaluated in a rigorous manner. The present article provides an international review of such systems. METHODS: The literature on integrated care covered the period from 1997 to 2010, inclusive. Some 2,496 citations were identified from Age Line, PsycINFO, CINAHAL and MedLine and were reviewed. To be included in this paper, articles had to provide a good description of the care delivery system and good quality evaluations. Only nine articles were retained. Most of the articles reviewed described some form of coordinated care without evaluation. RESULTS: There were essentially two types of models of integrated care delivery for the frail elderly. One was a smaller, community-based model that relied on cooperation across care providers, focused on home and community care, and played an active role in health and social care coordination. The second type of model was a large scale model that could be applied at a national/provincial/state, or large regional health authority, level, had a single administrative authority and a single budget, and included both home/community and residential services. DISCUSSION: Integrated care delivery can be achieved in various ways. Irrespective of which model is adopted, some of the key factors to be considered are how care can be coordinated effectively across different types of services, and how all the care provider organizations can be coordinated to ensure continuity of care for frail elderly persons. PMID- 22088902 TI - Medical, environmental and personal factors of disability in the elderly in Spain: a screening survey based on the International Classification of Functioning. AB - OBJECTIVES: The International Classification of Functioning, Disability and Health (ICF) advocates a multifactorial and multifaceted conceptualization of disability. The objective of this study was to ascertain major medical, environmental and personal determinants of severe/extreme disability among the elderly population in Spain. The assessment scheme was consistent with the ICF model of disability. METHODS: Nine populations contributed probabilistic or geographically-defined samples following a two-phase screening design. The Mini Mental State Examination and the 12-item version of the World Health Organization Disability Assessment Schedule, 2(nd) ed. (WHO-DAS II), were used as cognitive and disability screening tools, respectively. Positively screened individuals underwent clinical work-up for dementia and were administered the 36-item version of the WHO-DAS II to estimate ICF disability levels. We used logistic regression for the purposes of data combination, adjusted for age and sex in all analyses. RESULTS: The sample was composed of 503 participants aged >= 75 years. Alzheimers disease and depression were highly predictive of severe/extreme disability (OR: 17.40, 3.71). Good access to social services was strongly associated with a low level or absence of disability (OR: 0.05 to 0.18). Very difficult access to services and having dementia or another psychiatric disorder were associated with an increase in disability (OR: 66.06). There was also a significant interaction effect between access to services and neurological disorders (OR: 12.74). CONCLUSIONS: Disability is highly prevalent among the Spanish elderly and is influenced by medical, social and personal factors. Disability could potentially be reduced by ensuring access to social services, preventing dementia and stroke, and treating depression. PMID- 22088904 TI - [Prevalence and annual risk of tuberculosis infection in the school population aged 7 years old in Ceuta (Spain)]. AB - OBJECTIVE: To determine the prevalence of tuberculosis infection and annual risk of infection in the school population of Ceuta. METHOD: A cross-sectional study was conducted. A tuberculin test (2UT RT-23 Tween 80) was given to 7-year-old schoolchildren in Ceuta in 2008. A positive result was considered as an induration of >=5 mm at 72 hours in unvaccinated children. RESULTS: A total of 612 children were studied. The prevalence of tuberculosis infection was 0.98% (95% confidence interval with a 2.5% margin of error). The distribution showed differences among three health areas, and was greatest in the most deprived area (2.07%). The annual risk of infection was 0.15%. CONCLUSIONS: According to the most recent studies, the prevalence of tuberculosis infection in Ceuta is one of the highest of Spain. Our results do not agree with the epidemiological data for tuberculosis in Ceuta, which also includes imported cases. PMID- 22088905 TI - [Gender inequalities in health deterioration as a result of informal care in Spain]. AB - OBJECTIVES: To analyze differences in the characteristics of care provided by women and men to dependent persons, and their association with the perception of health deterioration in both sexes. METHODS: We performed a nationwide cross sectional study with data obtained from the 2008 Spanish Survey on Disability, Personal Autonomy and Dependence, based on a sample size of 7,512 principal caregivers. A descriptive analysis was performed of the characteristics of the care provided (tasks performed, intensity, frequency and duration) by sex. A multivariate logistic regression analysis was carried out to explore the association between the caregivers' perceptions of deteriorated health and the variables related to care, adjusted by sociodemographic characteristics. RESULTS: Most (74%) of the caregivers in the sample were women. Women more frequently perceived a deterioration in their health as a result of providing care than did men (37% and 21%, respectively). Women provided care with greater intensity and more frequently performed the tasks most associated with deteriorated health (personal hygiene, assistance in feeding, etc.). Men more frequently carried out tasks related to care outside the home (going to the doctor, shopping, etc.), all of which acted as a protective factor against health deterioration. The intensity of care was a risk factor for the perception of health deterioration in both sexes, while frequency and duration were also risk factors in women. CONCLUSIONS: The greater health deterioration perceived by women is related to gender inequalities in the characteristics of the care provided. Interventions in informal caregivers should be sensitive to these gender inequalities. PMID- 22088906 TI - [Characteristics of intravenous drug users who share injection equipment in Catalonia (Spain)]. AB - OBJECTIVES: To estimate the prevalence of direct and indirect syringe sharing among intravenous drug users (IDUs) attending a harm reduction center in Catalonia (Spain) and to identify factors associated with risk behaviors. METHODS: A cross-sectional study was conducted between 2008 and 2009 in harm reduction centers. Behavioral data were collected using anonymous questionnaires administered by trained interviewers. RESULTS: Of the 748 respondents, 31.5% had shared syringes at least once in the previous 6 months and 55.2% reported sharing injection paraphernalia (spoons, water, filters). A higher risk of syringe sharing was found among IDUs who injected daily (OR=1.5), injected cocaine (OR=1.6), had less than half their supply of syringes from a free source (OR=2.5), had an IDU sexual partner (OR=1.8) or who reported indirect sharing (OR=4.1). A higher risk of indirect sharing was found in respondents who had an illegal source of income (OR=1.5), injected daily (OR=1, 5), injected cocaine (OR=1.4), reported sharing syringes (OR=3.9), or who reported a previous overdose (OR=1.5). CONCLUSIONS: Despite the widespread use of harm reduction programs in Catalonia, a significant proportion of IDUs continue to practise injection related risk behaviors. Further reductions in risk behaviors could be achieved by improving access to all sterile injecting equipment, especially among cocaine injectors and IDUs who inject frequently, and by including IDU sexual partners within the current network of harm reduction centers. PMID- 22088907 TI - [Promoting routine human immunodeficiency virus testing in primary care]. AB - OBJECTIVES: To promote human immunodeficiency virus (HIV) testing in the primary care setting and to describe patients' attitudes toward this practice. METHODS: A non-randomized intervention was conducted on five physicians of an urban primary care center attending patients aged 18-65 years old, who were scheduled to undergo blood tests for other reasons. The patients were systematically offered HIV blood testing if they reported having had sex without a condom with a person of unknown HIV status. Not being tested required active refusal. The intervention period was from October to December 2008 and the control period was from October to December 2007. The main variable was the difference in the number of HIV tests requested. The proportion of patients accepting the test was also analyzed. RESULTS: Demographic factors were similar in patients in the two periods. The number of HIV tests increased from 3.7% (22/599) to 27.2% (212/780), p <0.001. A total of 209 patients were offered the HIV test. Their mean age was 45.6 years (SD 11.7), 141 were women (68%) and 11 were born outside Spain (5%). One hundred and ninety-five patients (93%) admitted the possibility of having been or being at risk. Of these patients, only three (1.5%), refused the HIV test. CONCLUSIONS: Routine HIV testing in the primary care setting is feasible and few patients refuse to be tested. PMID- 22088908 TI - [Analysis of drug advertising in Spanish gynecology journals]. AB - OBJECTIVES: To determine advertising pressure in three Spanish gynecology journals, to describe the characteristics of the drugs advertised and to analyze compliance with current regulatory standards in drug advertisements. METHODS: We identified the number of advertisements, the characteristics of the drugs advertised, the minimum information required by legislation and the advertising message in the selected journals. RESULTS: A total of 139 advertisements were identified, corresponding to 33 distinct products (28 prescription medicines and five over-the-counter drugs). Advertising pressures were 18.13% in Progresos de Obstetricia y Ginecologia, 16.18% in Acta Ginecologica and 5.21% in Clinica e Investigacion en Ginecologia y Obstetricia. Legislative failure occurred in 82.14% of the advertisements and in 22.22% of slogans, while 41.46% of advertising messages were misleading. CONCLUSION: A critical attitude to advertising among health professionals is advisable. Information contained in advertisements should be contrasted with official and other independent sources. PMID- 22088909 TI - [Scientific-professional production on the ICF disability model in Spain. A literature review (2001-2010)]. AB - OBJECTIVES: To quantify the use of the International Classification of Functioning, Disability and Health (ICF) in Spain on the basis of published reports, and to compare this use with that in other European countries. METHODS: We reviewed the scientific literature published by, or with the participation of, authors having Spanish institutional affiliations in Spanish or international journals between May 2001 and June 2010. RESULTS: A total of 47 papers were identified, with a recent annual increase in those published in English. There was a predominance of theoretical journals (53.1%) and those specializing in mental health, rehabilitation and disability, with a medium or low impact factor. The World Health Organization-Disability Assessment Schedule (WHODAS-II) was used in 27.6% of publications. Most studies addressed adult populations with mental illness. Spain ranked midway in the table of European countries (fifth by Medline references). CONCLUSIONS: This review suggests that the effective application of the ICF in Spain is limited but is increasing and is internationally co ordinated. The main fields of application are theoretical and diagnostic, in various clinical, rehabilitation and population-based contexts and, to a much lesser extent, in health services. PMID- 22088910 TI - Harm reduction, students and pleasure: an examination of student responses to a binge drinking campaign. AB - BACKGROUND: Recent debates about 'binge drinking' in New Zealand have positioned alcohol consumption amongst young drinkers as of concern. Research notes that students drink more heavily than their peers and that they have a higher incidence of alcohol related harms. In response, a harm reduction campaign aimed at first year university students was developed at a New Zealand university. METHODS: This mixed methods study used questionnaires (225) and a small number of semi-structured interviews (4) to elicit student responses to the harm reduction campaign. RESULTS: The majority of students in this study can be characterised as binge drinkers, although their drinking does not appear to cause them concern. The term 'binge drinking' is explored in three developed categories; 'light', 'moderate' and 'heavy' bingeing. Results are considered within a discussion of pleasure as a hindrance to harm reduction campaigns. CONCLUSIONS: The concept of 'determined drunkenness' and the notion of pleasure are important in students' motivations for drinking and may contribute to the resistance they have in viewing their alcohol consumption as concerning. It is argued that students already felt that they exercised control over their drinking for pleasure and this produced contradictions in responses towards the campaign compared to actual behaviour. PMID- 22088911 TI - Maybe not perfect-but surely good enough? PMID- 22088912 TI - Motor vehicle deaths among American Indian and Alaska Native populations. AB - In the United States, the American Indian and Alaska Native (AI/AN) population has the highest motor vehicle death rate, which is significantly greater than that of any other race or ethnic group. To better understand why this significant disparity exists and how to eliminate it, the authors conducted a systematic review of the published scientific literature. Included studies were published between January 1, 1990, and January 31, 2011, and identified risk factors, or implemented and tested interventions, targeting motor vehicle deaths among the AI/AN population. Only 14 papers met the study's inclusion criteria. Most of the epidemiologic studies explored alcohol use as a risk factor for deaths of both motor vehicle occupants and pedestrians; few studies addressed risk factors specifically for pedestrians. All of the intervention studies focused on mitigating risks for motor vehicle occupants. On the basis of the authors' review, injury prevention interventions that are multifaceted and involve partnerships to change policy, the environment, and individual behavior can effectively mitigate motor-vehicle-related deaths among AI/ANs. Priority should be given to implementing interventions that address pedestrian safety and to sound investment in the states with the highest AI/AN motor vehicle death rates because reducing their burden can dramatically reduce the overall disparity. PMID- 22088913 TI - Protein restriction to pregnant rats increases the plasma levels of angiotensin II and expression of angiotensin II receptors in uterine arteries. AB - Whether gestational protein restriction affects the renin-angiotensin system (RAS) in uterine artery remains unknown. In this study, we hypothesized that gestational protein restriction alters the expression of RAS components in uterine artery. In study one, time-scheduled pregnant Sprague Dawley rats were fed a normal or low-protein (LP) diet from Day 3 of pregnancy until they were killed at Days 19 and 22. The uterine arteries were collected and used for gene expression of Ace, Ace2, Agtr1a, Agtr1b, Agtr2, Esr1, and Esr2 by quantitative real-time PCR and/or Western blotting. LP increased plasma levels of angiotensin II in pregnant rats. In the uterine artery, the expressions of Agtr1a, Agtr1b, and Esr1 were increased by LP at Days 19 and 22 of pregnancy, whereas the abundance of AGTR1 and AGTR2 was increased by LP at Day 19 of pregnancy. The expression of Ace2 was not detectable in rat uterine artery. In study two, virgin female rats were ovariectomized and implanted with either 17beta-estradiol (E2), progesterone (P4), both E2 and P4, or placebo pellets until they were killed 7 days later. In rat uterine artery, E2 and P4 reduced the expression of Agtr1a, and E2 increased the expression of Agtr1b and Agtr2, but neither E2 nor P4 regulated the expression of Ace. These results indicate that gestational protein restriction induces an increase in Agtr1 expression in uterine artery, and thus may exacerbate the vasoconstriction to elevated angiotensin II present in maternal circulation, and that female sex hormones also play a role in this process. PMID- 22088914 TI - Bovine DNA methylation imprints are established in an oocyte size-specific manner, which are coordinated with the expression of the DNMT3 family proteins. AB - A subset of genes, known as imprinted genes, is present in the mammalian genome. Genomic imprinting governs the monoallelic expression of these genes, depending on whether the gene was inherited from the sperm or the egg. This parent-of origin specific gene expression is generally dependent on the epigenetic modification, DNA methylation, and the DNA methylation status of CpG dinucleotides residing in loci known as differentially methylated regions (DMRs). The enzymatic machinery responsible for the addition of methyl (-CH(3)) groups to the cytosine residue in the CpG dinucleotides are known as DNA methyltransferases (DNMTs). Correct establishment and maintenance of methylation patterns at imprinted genes has been associated with placental function and regulation of embryonic/fetal development. Much work has been carried out on imprinted genes in mouse and human; however, little is known about the methylation dynamics in the bovine oocyte. The primary objective of the present study was to characterize the establishment of methylation at maternally imprinted genes in bovine growing oocytes and to determine if the expression of the bovine DNMTs-DNMT3A, DNMT3B, and DNMT3L-was coordinated with DNA methylation during oocyte development. To this end, a panel of maternally imprinted genes was selected (SNRPN, MEST, IGF2R, PEG10, and PLAGL1) and putative DMRs for MEST, IGF2R, PEG10, and PLAGL1 were identified within the 5' regions for each gene; the SNRPN DMR has been reported previously. Conventional bisulfite sequencing revealed that methylation marks were acquired at all five DMRs investigated in an oocyte size-dependent fashion. This was confirmed for a selection of genes using pyrosequencing analysis. Furthermore, mRNA expression and protein analysis revealed that DNMT3A, DNMT3B, and DNMT3L are also present in the bovine oocyte during its growth phase. This study demonstrates for the first time that an increase in bovine imprinted gene DMR methylation occurs during oocyte growth, as is observed in mouse. PMID- 22088915 TI - Improving sperm cryopreservation with antifreeze proteins: effect on gilthead seabream (Sparus aurata) plasma membrane lipids. AB - Changes in the plasma membrane lipid composition have been related to a decrease in sperm quality during cryopreservation. Antifreeze proteins (AFPs) have been tested in different species because of their ability to depress the freezing point and their potential interaction with membranes, but controversial effects were reported. In the present study we analyzed separately the lipid composition of two sperm membrane domains, head plasma membrane (HM) and flagellar membrane (FM), after cryopreservation with an extender containing 5% dimethyl sulfoxide (DMSO) either alone or with AFPI or AFPIII (1 MUg/ml). We used sperm from a teleost, Sparus aurata, because the lack of acrosome avoids changes of lipid profiles due to capacitation process or acrosomal losses during freezing/thawing. Comparing with the control (cryopreservation with 5% DMSO alone), the addition of AFPIII increased the velocity, linearity of movement, and percentage of viable cells. In addition, freezing with DMSO alone increased the phosphatidyl-serine content as well as the saturated fatty acids and decreased the unsaturated ones (mainly polyunsaturated) both in HM and FM. These changes in the lipid components were highly avoided with the addition of AFPIII. HM had a higher amount of saturated fatty acids than FM and was more affected by cryopreservation without AFPs. The percentage of viable cells was positively correlated with the amount of unsaturated fatty acids in the HM, whereas the motility parameters were positively correlated with both FM and HM amount of unsaturated fatty acids. AFPs, especially AFPIII, seem to have interacted with unsaturated fatty acids, stabilizing the plasma membrane organization during cryopreservation and contributing to improve sperm quality after thawing. PMID- 22088917 TI - Meiotic genetics moves forward with SPATA22 (repro42). AB - This commentary provides a summary of existing meiotic mutants affecting the synaptonemal complex and meiotic recombination in order to contextualize the recent discovery of SPATA22/repro42 through ENU mutagenesis. PMID- 22088916 TI - Developmental exposure to xenoestrogens at low doses alters femur length and tensile strength in adult mice. AB - Developmental exposure to high doses of the synthetic xenoestrogen diethylstilbestrol (DES) has been reported to alter femur length and strength in adult mice. However, it is not known if developmental exposure to low, environmentally relevant doses of xenoestrogens alters adult bone geometry and strength. In this study we investigated the effects of developmental exposure to low doses of DES, bisphenol A (BPA), or ethinyl estradiol (EE(2)) on bone geometry and torsional strength. C57BL/6 mice were exposed to DES, 0.1 MUg/kg/day, BPA, 10 MUg/kg/day, EE(2), 0.01, 0.1, or 1.0 MUg/kg/day, or vehicle from Gestation Day 11 to Postnatal Day 12 via a mini-osmotic pump in the dam. Developmental Xenoestrogen exposure altered femoral geometry and strength, assessed in adulthood by micro-computed tomography and torsional strength analysis, respectively. Low-dose EE(2), DES, or BPA increased adult femur length. Exposure to the highest dose of EE(2) did not alter femur length, resulting in a nonmonotonic dose response. Exposure to EE(2) and DES but not BPA decreased tensile strength. The combined effect of increased femur length and decreased tensile strength resulted in a trend toward decreased torsional ultimate strength and energy to failure. Taken together, these results suggest that exposure to developmental exposure to environmentally relevant levels of xenoestrogens may negatively impact bone length and strength in adulthood. PMID- 22088918 TI - The role of autophagy in human endometrium. AB - Autophagy appears to play an important role in the normal development and maintenance of homeostasis in a variety of tissues, including the female reproductive tract. However, the role of autophagy and the association between autophagy and apoptosis in cyclic remodeling of the human endometrium have not been described. Therefore, we investigated the involvement of autophagy during the human endometrial cycle and its association with apoptosis. Endometrial samples were obtained from 15 premenopausal, nonpregnant women who underwent hysterectomies for benign gynecological reasons. The autophagy-associated protein, microtubule-associated protein 1 light chain 3 alpha (MAP1LC3A), was immunolocalized, and its expression level was measured by Western blot analysis. Apoptosis was evaluated by measuring the expression level of cleaved caspase 3 protein. MAP1LC3A protein was primarily expressed within the endometrial glandular cells and increased during the secretory phase. The expression level of the membrane-bound form of MAP1LC3A (MAP1LC3A-II) also increased as the menstrual cycle progressed, reaching a maximum level during the late secretory phase. This pattern coincided with the expression of cleaved caspase 3. Furthermore, expression of MAP1LC3A-II and cleaved caspase 3 increased in the in vitro cultured endometrial cancer cells when estrogen and/or progesterone were withdrawn from the culture media to mimic physiological hormonal changes. These findings suggest that endometrial cell autophagy is directly involved in the cyclic remodeling of the human endometrium and is correlated with apoptosis. In addition, we inhibited autophagic processes using 3-methyladenine (3-MA) or bafilomycin A1 (Baf A1) to evaluate the role of autophagy in apoptosis induction in endometrial cancer cells. While the inhibition of autophagosome formation using 3-MA did not decrease apoptosis or cell death, the inhibition of autophagosome degradation by fusion with lysosomes using Baf A1 increased apoptosis and cell death, suggesting that the accumulation of autophagosomes induces apoptosis. Furthermore, Baf A1-induced apoptotic cell death was decreased by the apoptosis inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z VAD-FMK). In conclusion, these results indicate that autophagy is involved in the endometrial cell cycle affecting apoptosis and is most prominent during the late secretory phase. PMID- 22088919 TI - Probiotics can induce follicle maturational competence: the Danio rerio case. AB - In the present study, the effects of the probiotic Lactobacillus rhamnosus IMC 501 on the acquisition of oocyte maturational competence was examined in zebrafish (Danio rerio). L. rhamnosus administration induced the responsiveness of incompetent follicles (stage IIIa) to 17,20-dihydroxy-4-pregnen-3-one and their in vitro maturation. Acquisition of competence by the stage IIIa follicles was further validated by changes of lhr, mprb, inhbaa (activin betaA1), tgfb1, and gdf9 gene expression, which have recently emerged as key regulators of oocyte acquisition of maturational competence, and pou5f1 gene expression, which in other models has been shown to govern the establishment of developmental competence of oocytes. In addition, a DNA microarray experiment was conducted using the same follicles, and with relative gene ontology (GO) data analysis, the molecular effects of probiotic administration emerged. Molecular analysis using PCR-DGGE (denaturing gradient gel electrophoresis) approach, providing information about only the most abundant bacterial members of the microbial community, revealed that the probiotic was able to populate the gastrointestinal tract and modulate the microbial communities, causing a clear shift in them and specifically enhancing the presence of the lactic acid bacteria Streptococcus thermophilus. At the same time, PCR-DGGE analysis revealed that the probiotic was not directly associated with the ovaries. Finally, the effects of probiotic treatment on zebrafish follicle development were also analyzed by FPA (focal plane array) Fourier transform-infrared (FT-IR) imaging, a technique that provides the overall biochemical composition of samples. Changes were found above all in stage IIIa follicles from probiotic-exposed females; the modifications, observed in protein secondary structures as well as in hydration and in bands related to phosphate moieties, allowed us to hypothesize that probiotics act at this follicle stage, affecting the maturation phase. PMID- 22088920 TI - Incidence rates and risk factors for vascular events in patients with essential thrombocythemia: a multicenter study from Korea. AB - BACKGROUND: Essential thrombocythemia (ET) is classified as a Philadelphia chromosome-negative classic myeloproliferative neoplasm. ET is a clonal stem cell disorder that is often associated with JAK2 mutations and shares phenotypic and pathogenetic similarities with other myeloproliferative neoplasms. Hemorrhagic complications and arterial and venous thrombosis are common in patients with ET. The aim of this retrospective analysis was to assess the cumulative incidence rate and risk factors for thrombohemorrhagic events in patients with ET based on a multicenter study in Korea. PATIENTS AND METHODS: A total of 239 patients with ET, from February 1995 to April 2011, were retrospectively analyzed from 4 Korean academic institutions. Data were collected through the review of medical records, and vascular events were confirmed by diagnostic procedures for establishing thrombosis and hemorrhagic complications. RESULTS: Of the patients (median age, 61 years; median follow-up, 51.8 months), 32 (13.4%) experienced thrombohemorrhagic complications. The 10-year cumulative incidence rate showed a 20.6% incidence of thrombohemorrhagic events. In univariate analysis, the presence of JAK2 mutations, high-risk group, previous thrombohemorrhagic events, and >60 years old were shown to have higher incidences of vascular events than any other factors. In multivariate analysis, previous thrombotic events and JAK2 mutations were independent risk factors for vascular events (hazard ratio, 2.907 [95% CI, 1.142-7.406], P =.025; and 4.146 [95% CI 1.227-14.018], P = 0.022). CONCLUSION: Previous thrombotic history and the JAK2 V617F mutation were associated with a higher 10-year cumulative incidence rate of thrombohemorrhagic events. PMID- 22088921 TI - Internal gating and somatization disorders: proposing a yet un-described neural system. AB - Medically unexplained symptoms (MUS) are a major medical burden and our current understanding of the pathophysiological process leading to their development remains minimal. While research has strongly linked chronic stress to the development of MUS the exact mechanisms and the reason for the many variations in the resultant symptomatology remain unclear. In this paper we advance the hypothesis that an internal (visceral) sensory gating system must exist akin to the much better studied external sensory gating system. The hypothesis is based on the observations that under normal conditions sensations of internal organs do not reach consciousness (i.e., filtered or gated out on a subconscious or preattentive level). As visceral sensations are usually perceived only when there is a pathological process affecting the organ, then failure of this internal gating system leading to the sensations arriving to consciousness must be interpreted by the brain to indicate pathology in this organ. If the hypothesis proves to be true and such a system does exist, the implications are many and significant including developing methods for assessing the system and possibly correcting it. PMID- 22088922 TI - Why the spleen is a very rare site for metastases from epithelial cancers. AB - It is not known why metastases from epithelial cancers are rare in the spleen, yet common in the other major organs of the reticuloendothelial system in which, like the spleen, leucocytes display a prolonged physiological intravascular transit time. Another unresolved issue that at first seems unrelated to splenic metastases is the inconsistency between the concept of physiological granulocyte disposal through granulocyte ageing and the observation that granulocytes leave the blood in an exponential fashion (half-time 7 h), which implies random disposal. Intravascular granulocytes pass through the spleen with an exponential distribution of transit times (mean 10 min). The spleen is highly active in physiological granulocyte destruction so it is suggested that the variation in times of exposure to the splenic microenvironment converts the age-dependent granulocyte destruction observed ex vivo into the random process observed in vivo, probably through exposure to apoptosis-inducing signals. This leads to the second hypothesis, which is that cancer cells fail to survive in the spleen as a result of these pro-apoptotic signals. PMID- 22088923 TI - Pyridoxal 5'-phosphate (PLP) deficiency might contribute to the onset of type I diabetes. AB - The incidence of type I diabetes is rising worldwide, particularly in young children. Type I diabetes is considered a multifactorial disease with genetic predisposition and environmental factors participating. Currently, despite years of research, there is no consensus regarding the factors that initiate the autoimmune response. Type I diabetes is preceded by autoimmunity to islet antigens, among them the protein glutamic acid decarboxylase, GAD-65. Pyridoxal 5'-phosphate (PLP) is formed from vitamin B6 by the action of pyridoxal kinase. Interaction of GAD65 with PLP is necessary for GAD65-mediated synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). PLP is also a required cofactor for dopamine synthesis by L-aromatic decarboxylase (L-AADC). Both GAD65 and L AADC are expressed in pancreatic islets. Here it is proposed that lack of the vitamin B6 derivative pyridoxal 5'-phosphate might contribute to the appearance of pancreatic islet autoimmunity and type I diabetes onset. PMID- 22088924 TI - Analysis of 4999 online physician ratings indicates that most patients give physicians a favorable rating. AB - BACKGROUND: Many online physician-rating sites provide patients with information about physicians and allow patients to rate physicians. Understanding what information is available is important given that patients may use this information to choose a physician. OBJECTIVES: The goals of this study were to (1) determine the most frequently visited physician-rating websites with user generated content, (2) evaluate the available information on these websites, and (3) analyze 4999 individual online ratings of physicians. METHODS: On October 1, 2010, using Google Trends we identified the 10 most frequently visited online physician-rating sites with user-generated content. We then studied each site to evaluate the available information (eg, board certification, years in practice), the types of rating scales (eg, 1-5, 1-4, 1-100), and dimensions of care (eg, recommend to a friend, waiting room time) used to rate physicians. We analyzed data from 4999 selected physician ratings without identifiers to assess how physicians are rated online. RESULTS: The 10 most commonly visited websites with user-generated content were HealthGrades.com, Vitals.com, Yelp.com, YP.com, RevolutionHealth.com, RateMD.com, Angieslist.com, Checkbook.org, Kudzu.com, and ZocDoc.com. A total of 35 different dimensions of care were rated by patients in the websites, with a median of 4.5 (mean 4.9, SD 2.8, range 1-9) questions per site. Depending on the scale used for each physician-rating website, the average rating was 77 out of 100 for sites using a 100-point scale (SD 11, median 76, range 33-100), 3.84 out of 5 (77%) for sites using a 5-point scale (SD 0.98, median 4, range 1-5), and 3.1 out of 4 (78%) for sites using a 4-point scale (SD 0.72, median 3, range 1-4). The percentage of reviews rated >=75 on a 100-point scale was 61.5% (246/400), >=4 on a 5-point scale was 57.74% (2078/3599), and >=3 on a 4-point scale was 74.0% (740/1000). The patient's single overall rating of the physician correlated with the other dimensions of care that were rated by patients for the same physician (Pearson correlation, r = .73, P < .001). CONCLUSIONS: Most patients give physicians a favorable rating on online physician rating sites. A single overall rating to evaluate physicians may be sufficient to assess a patient's opinion of the physician. The optimal content and rating method that is useful to patients when visiting online physician-rating sites deserves further study. Conducting a qualitative analysis to compare the quantitative ratings would help validate the rating instruments used to evaluate physicians. PMID- 22088925 TI - The capacity of acute stress disorder to predict posttraumatic psychiatric disorders. AB - BACKGROUND: One rationale for establishing the acute stress disorder diagnosis was to identify recently trauma-exposed people who may develop later posttraumatic stress disorder (PTSD). This study conducted a multi-site assessment of the extent to which ASD predicts subsequent PTSD, and also major depressive disorder, panic disorder, agoraphobia, social phobia, specific phobia, generalized anxiety disorder, and substance use disorder, 12 months after trauma. METHOD: Consecutive admissions to 5 major trauma hospitals across Australia (N = 1084) were assessed during hospital admission and within one month of trauma exposure and subsequently re-assessed for psychiatric disorder 12 months after the initial assessment (N = 859). RESULTS: Whereas 120 (10%) patients met criteria for ASD in the initial month after trauma, 83 (10%) met criteria for PTSD, and 268 (31%) had any psychiatric disorder at 12 months. In terms of those diagnosed with ASD, 28 (36%) subsequently met criteria for PTSD and 50 (65%) subsequently developed any psychiatric disorder. CONCLUSIONS: Whereas the majority of people with ASD subsequently develop a psychiatric disorder, most people with a disorder at 12 months do not initially display ASD. PMID- 22088926 TI - Interaction of the BcII glucocorticoid receptor polymorphism and childhood abuse in Bulimia Nervosa (BN): relationship to BN and to associated trait manifestations. AB - We recently documented a gene-environment interaction suggesting that individuals with Bulimia Nervosa (BN) differed from normal eaters as to the combined presence of the low-function allele of the glucocorticoid receptor polymorphism, BcII, and childhood abuse. The present study examined the extent to which any such interaction effect may have been attributable to behavioral impulsivity, sensation seeking, affective instability or depression. We had 174 bulimic and 130 nonbulimic women provide blood for genetic assays, and measured psychopathological traits and childhood abuse using structured interviews and self-report questionnaires. As expected, we observed a significant BcII * abuse interaction indicating genetic and environmental susceptibilities to co-occur significantly more often in bulimic than in nonbulimic individuals. The BcII * abuse interaction was attenuated when levels of depression were accounted for, but was surprisingly unaffected by controls for motoric impulsivity, sensation seeking or affective instability. Our findings suggest that stress-induced alterations in glucocorticoid sensitivity contribute to BN and depressive disturbances--without being associated with the behavioral/affective dysregulation seen in many BN sufferers. We discuss theoretical and clinical implications of these observations. PMID- 22088927 TI - Incidence of severe work-related injuries among young adult workers in Brazil: analysis of compensation data. AB - OBJECTIVES: To obtain national estimates of the annual cumulative incidence and incidence density of severe non-fatal injuries using compensation benefits data from the Brazilian National Social Security Institute (INSS), and to describe their sociodemographic distribution among workers aged under 25 years. METHODS: Data are records of health-related compensation benefits from the Ministry of Social Insurance's information system of compensation benefits of the INSS recorded in 2006. Injuries were cases classified under chapter XIX, ICD-10. The assessment of their relation with work was made by INSS's occupational physician experts. The study population comprised young workers aged 16-24 years. RESULTS: 59,381 workers received compensation benefits for injuries in the study year. Among them 14,491 (24.4%) were work related, 12,501 (86.3%) were male and 1990 were female workers (13.7%). The annual cumulative incidence rate of work-related injuries (ACI-WI) was 2.9*1000 workers, higher among men (4.2*1000) than women (1.0*1000). The incidence density rate (IDR-WI) was 0.7/1000 full-time equivalent (FTE), higher for men (0.97/1000 FTE) than women (0.24/1000 FTE). Both morbidity measures were higher in the younger group (16-19 years), and inversely related to wage, especially for women in the younger group. Logging, extraction, food/beverage and construction industries had higher ACI-WI and IDR-WI for adolescents and young adult workers of both sex groups. CONCLUSIONS: These findings suggest that the Brazilian labour laws limiting young adult workers in hazardous settings need to be expanded, adding occupations in other extractive industries and certain types of work in the food/beverage manufacturing industries. Social inequalities associated with sex need to be examined further with more detailed data. PMID- 22088928 TI - Injury prevention and risk communication: a mental models approach. AB - Individuals' decisions and behaviour can play a critical role in determining both the probability and severity of injury. Behavioural decision research studies peoples' decision-making processes in terms comparable to scientific models of optimal choices, providing a basis for focusing interventions on the most critical opportunities to reduce risks. That research often seeks to identify the 'mental models' that underlie individuals' interpretations of their circumstances and the outcomes of possible actions. In the context of injury prevention, a mental models approach would ask why people fail to see risks, do not make use of available protective interventions or misjudge the effectiveness of protective measures. If these misunderstandings can be reduced through context-appropriate risk communications, then their improved mental models may help people to engage more effectively in behaviours that they judge to be in their own best interest. If that proves impossible, then people may need specific instructions, not trusting to intuition or even paternalistic protection against situations that they cannot sufficiently control. The method entails working with domain specialists to elicit and create an expert model of the risk situation, interviewing lay people to elicit their comparable mental models, and developing and evaluating communication interventions designed to close the gaps between lay people and experts. This paper reviews the theory and method behind this research stream and uses examples to discuss how the approach can be used to develop scientifically validated context-sensitive injury risk communications. PMID- 22088929 TI - Increased risk of cancer among gout patients: a nationwide population study. AB - OBJECTIVE: Few studies have investigated the association between gout and cancer. The present study examined the relative risk of cancer in a nationwide cohort. METHODS: The primary data source was the National Health Insurance database of Taiwan. Data recorded between 2000 and 2008 for subjects >=20 years and with no history of malignancy were included for the analysis. A gout case definition was defined by records of gout diagnosis and anti-gout treatment (urate-lowering drugs, including allopurinol, benzbromazone, probenacid and sulfinpyrazone, and colchicine). Cox proportional hazards models were used to examine the association between gout and cancer. RESULTS: A total of 694,361 patients (355,278 men, 339,083 women) were included; among them, 25,943 had a history of gout. Mean age (+/-standard deviation) was 42.3+/-16.3 years. During 5,471,272 patient-years of follow-up, cancer was detected in 24,088 patients (1745 with gout and 22,343 controls). The most cancers were liver, lung, and colonic cancers. The overall incidence of cancer was significantly higher among gout patients than controls (8.7 vs. 4.2 cases per 1000 patient-years, P<0.001). After adjustment for age and sex, gout was found to be associated with a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.10-1.21; P<0.001) for cancer. Gout was most closely associated with prostate cancer, with an age- and sex-adjusted HR of 1.71 (1.45 2.02). On the other hand, gout tended to have an inverse, albeit insignificant, association with breast cancer (adjusted HR, 0.81; 95% CI, 0.63-1.04). CONCLUSION: Gout was associated with increased risk of cancer, particularly that of prostate cancer in males. PMID- 22088930 TI - Frequency of hospitalization and severe events in 497 spondylarthritis patients treated with anti-TNF drugs: comparisons with 423 RA patients. PMID- 22088931 TI - Proximal symphalangism and premature ovarian failure. AB - Proximal symphalangism is a rare autosomal dominant affection responsible for multiple joint ankylosis, it results from NOG gene mutation whose locus is on 17q21-22. This gene may be involved in secretory functions of glands such as ovarian function. Premature ovarian failure is idiopathic in 80% of cases but may be secondary to multiple etiologies including genetic. We report the case of a patient with proximal symphalangism and premature ovarian failure, and we discuss the possibility of genetic relationship between the two anomalies. PMID- 22088932 TI - Supraclavicular nerve entrapment syndrome. AB - Supraclavicular nerve entrapment syndrome, although rare, should be considered among the causes of anterior shoulder girdle pain. This syndrome is usually related to anatomic variants (involving the bone structures, fibrous bands, or muscles and tendons). Computed tomography is the most useful investigation. Medications used to treat neuropathic pain may provide relief. Otherwise, a local glucocorticoid injection or even surgical decompression should be considered. PMID- 22088933 TI - Assessment of hand trabecular bone texture with high resolution direct digital radiograph in rheumatoid arthritis: a case control study. AB - OBJECTIVES: Rheumatoid arthritis is characterized by an early inflammatory related periarticular osteopenia. A new high resolution direct digital X-ray device has been recently developed to provide bone texture analysis which is designed to assess changes in trabecular bone architecture. For the first time, we have evaluated trabecular bone texture impairment in rheumatoid arthritis patients compared to healthy controls. METHODS: In this cross-sectional study, the reproducibility was assessed by three separate digital X-rays of the right hand, with repositioning in 14 late rheumatoid arthritis patients and 14 healthy subjects. Then, trabecular bone texture of the MCP2 and MCP3 from patients enrolled in a prospective cohort of 78 rheumatoid arthritis patients was compared with that of 50 healthy subjects, using three texture parameters: Hmean, co occurrence and run-length. RESULTS: The coefficients of variation of the high resolution direct digital X-ray measurements ranged from 0.5 to 1.8%. Only the Hmean parameter was significantly decreased in rheumatoid arthritis patients compared to healthy subjects at MCP2 (0.637+/-0.040 vs. 0.654+/-0.032, P<0.05) and at MCP3 (0.646+/-0.044 vs. 0.665+/-0.037, P<0.05). This reduction was significantly correlated to disease activity. CONCLUSIONS: This study demonstrated both the good reproducibility of the high resolution digital X-ray measurements and the trabecular bone texture impairment at MCP joints in rheumatoid arthritis patients. In addition to provide a high resolution hand radiograph, this technique may represent an interesting tool to easily quantify periarticular osteopenia with a low radiation dose. PMID- 22088934 TI - Development of inflammatory bowel disease during anti-TNF-alpha therapy for inflammatory rheumatic disease: a nationwide series. AB - OBJECTIVES: To describe cases of new onset of inflammatory bowel disease (IBD) in patients with inflammatory rheumatic disease (IRD) receiving anti-TNF-alpha therapy. METHODS: A call for observations of such cases was sent to members of the French "Club rhumatismes et inflammation". Only patients without intestinal symptoms before introduction of anti TNF-alpha agents were included. RESULTS: During a 2-year period, 16 patients were declared: nine men and seven women, mean age 41.5 +/- 17.4 years, 12 patients with ankylosing spondylitis, one with rheumatoid arthritis, one with psoriatic arthritis and two juvenile idiopathic arthritis with enthesitis related arthritis. Overall, 14 patients received etanercept and two had infliximab. The meantime frame between onsets of anti-TNF- alpha drugs and development of IBD was 29.3 +/- 20.1 months. According to endoscopic and histological findings, IBD was classified as typical Crohn's disease in eight cases, Crohn's-like disease in six cases, indeterminate in one case and definite ulcerative colitis in one case. For all cases, each TNF-alpha blocking agent was discontinued and replaced by another monoclonal anti TNF-alpha antibody. After a mean follow up period of 23.4 +/- 19.5 months, outcome was favorable without recurrent or flaring IBD. CONCLUSIONS: Paradoxical IBD may occur during anti TNF-alpha therapy for inflammatory rheumatic disease, mostly in patients with spondylarthropathies while receiving etanercept, at a frequency estimated to 0.15% in the French patients with spondylarthropathies exposed to TNF-alpha antagonists. The IBD mainly corresponded to Crohn's or Crohn's-like disease. On the contrary, new onset IBD is less frequently observed in other cases of IRD and with other TNF--alpha blockers. PMID- 22088935 TI - A self-administered questionnaire to screen the risk of dementia: a pilot study and the results of a comparison with the mini-mental state examination (MMSE). AB - Cognitive impairment is an age-related condition as the rate of cognitive decline rapidly increases with aging. The aim of this study was to screen the risk of cognitive decline in people over 60 years from 16 different Italian cities, by comparing the results of a self-administered questionnaire with the MMSE. We analyzed data from 203 persons aged 60 years and over, who voluntarily accepted to participate during the "Second Prevention Day for AD". A self-administered questionnaire, developed by clinicians of our Department of Aging, was distributed to all participants, in order to easily screen the risk of cognitive impairment. Then, all subjects underwent cognitive assessment by MMSE. We esteemed the risk of cognitive impairment of all participants basing on MMSE scores (no risk, mild and moderate risk) and we compared this assessment with the results obtained by the self-administered questionnaire. The comparison between the risk of cognitive impairment revealed by our questionnaire and the risk esteemed by MMSE resulted in a discrepancy in 43.96% of cases in no risk class. In mild risk group there was a discrepancy of results in 70.53% of subjects. In moderate risk class there was a discrepancy of results in 38.46% of individuals. Our questionnaire resulted to be accurate for the evaluation of patients with moderate risk of cognitive impairment. It showed a lower accuracy for the mild risk class, often overestimating the risk of cognitive decline. PMID- 22088936 TI - Topography of cortical thinning areas associated with hippocampal atrophy (HA) in patients with Alzheimer's disease (AD). AB - Prior studies have shown that patients with AD have decreased functional or structural connectivity between the hippocampus and other brain areas. To the best of our knowledge, however, there have been no studies investigating the topography of cortical thinning areas and correlations with HA using surface based morphometry of three-dimensional (3D) T1-weighted magnetic resonance (MR) images. Cortical thickness was measured using SBM, and hippocampal volume was measured using an automated method, in 219 patients with AD and 54 subjects with no cognitive impairment (NCI). A partial correlation model was used in analysis of cortical thinning related to HA. Cortical thinning areas related to HA were found mostly within areas associated with polysynaptic or direct pathways of the hippocampus, a finding consistent with the disconnection hypothesis. Therefore, the cortical atrophy related to HA in patients with AD may represent disrupted cortical brain networks in connection with HA. However, since the topography of HA-related cortical thinning in groups with Clinical Dementia Ratings (CDR) of 0.5 and 1 corresponded to the stages I-II and III-IV of Braak and Braak staging, respectively, we could not exclude the possibility of the "concomitant hypothesis," i.e. that these areas are affected concomitantly with the hippocampus. PMID- 22088937 TI - The effect of aging and dental status on the frequency of eating out. AB - Although many studies have investigated the effect of impaired dentition on eating habits and social expression, very few studies have evaluated the effect of age and dental status on the frequency of eating out, which was the purpose of the present study. A sample of 161 community-dwelling adults aged between 20 and 94 years of age was interviewed and then clinically examined to record dental and denture status. The bivariate analyses revealed that those who were eating out less often were more likely older, widowed, pensioners, with elementary or less than elementary education, suffering from hypertension, overweight or obese, with bad self-rated health, complaining for xerostomia, with difficulties chewing hard food and with fewer natural teeth. Multiple logistic regression analysis identified as significant predictors for less frequently eating out older age and low educational level. These results suggest that in the particular cultural environment the dental status is not an independent predictor of the frequency of eating out, but other biological and social factors play a more significant role. PMID- 22088938 TI - A pilot test of a combined tobacco dependence treatment and lung cancer screening program. AB - Lung cancer screening with computed tomography has demonstrated a significant reduction in mortality. While these findings are important for the lung cancer research field, the most important risk factor for lung cancer, i.e. smoking, should not be ignored. We performed a pilot study to examine the feasibility of delivering a program that included both tobacco dependence treatment and lung cancer screening. The objectives of this study were to: (1) estimate the proportion of smokers who complied with a 12-week treatment protocol that included both tobacco dependence treatment and lung cancer screening, (2) obtain preliminary estimates of abstinence and quit attempts at 4 and 6 months, and (3) obtain preliminary estimates of the cognitive social health information processing (C-SHIP) constructs and how they change following the intervention. In this randomized pilot study, 18 volunteers completed a 12-week protocol: half received the tobacco dependence treatment program before a CT scan (BCT) and the other received the CT scan first, followed by the treatment program (ACT). The treatment protocol included both nurse-delivered telephone counseling and either nicotine replacement therapy or varenicline. Only one person did not complete all follow-up evaluations. At 4 months post enrollment, the carbon monoxide confirmed quit rates were 33.3% in the BCT arm and 22.2% in the ACT arm (27.8% overall), and all but one had made a 24-h attempt to quit. At 6 months the confirmed abstinence decreased to 22.1% in the BCT arm and 11.1% in the ACT arm (16.7% overall), and 72.2% of participants had made a 24-h quit attempt. These preliminary results suggest that it might be better to deliver treatment before the screening test. Future randomized trials with a larger sample size are needed to confirm these findings. PMID- 22088939 TI - Immunosuppression and lung cancer of donor origin after bilateral lung transplantation. AB - Analysis of databases from transplant recipients revealed a 3-5 fold higher risk to develop de novo malignancies under continued immunosuppression. The underlying mechanisms are poorly understood. Here we describe a patient who received a bilateral lung transplantation for end-stage 'usual interstitial pneumonia' (UIP) resulting in idiopathic lung fibrosis. The recipient presented with a non-small cell lung carcinoma (NSCLC) in the donor lung 7 months later. Molecular and immunological typing of the tumor revealed a cancer of donor origin with a prominent intratumoral immune cell infiltrate without detectable effector function. This is a unique case of de novo outgrowth of a NSCLC of donor origin under continued immunosuppression, supporting the concept of tumor immunosurveillance in vivo. PMID- 22088940 TI - Placenta: predicting future health. PMID- 22088941 TI - Growth, metastasis, and expression of CCL2 and CCL5 by murine mammary carcinomas are dependent upon Myd88. AB - Previously we reported that lipopolysaccharide (LPS) treatment of murine mammary carcinomas resulted in decreased growth of the tumors. Here we show the decreased growth following LPS treatment was mediated through effects downstream of TLR4 and Myd88. Perhaps more notably, simply reducing TLR4 or Myd88 levels was sufficient to slow tumor growth rates. Moreover, reduced levels of Myd88 correlated with a significant reduction in lung metastasis as well as decreased CCL2 and CCL5 expression. To determine whether inhibiting Myd88 function could also alter tumor growth and chemokine expression we used a Myd88 homodimerization inhibitory peptide. Indeed, inhibiting Myd88 function in four different murine mammary carcinomas as well as the human breast cancer cell line MDA-MB-231 led to decreased growth as well as CCL2 and CCL5 expression. These data imply that Myd88 is important for growth and metastasis of breast cancer, and expression of at least two proinflammatory chemokines. PMID- 22088942 TI - Subsensory galvanic vestibular stimulation augments arterial pressure control upon head-up tilt in human subjects. AB - The vestibular system plays an important role in control of arterial pressure (AP) upon head-up tilt (HUT). To examine this role in human subjects, we previously compared changes in AP with and without high-amplitude galvanic vestibular stimulation (GVS), which is considered to obscure vestibular input. In contrast, regarding sensory function in skin and muscle, it has been documented that low-amplitude electrical stimulation improves both sensitivity and response. In the present study, we examined whether GVS of smaller amplitude improves AP control upon HUT. GVS was applied at the amplitude of the somatosensory threshold (0.3-0.8 mA), 0.1 mA over the threshold, and 0.1 and 0.2 mA below the threshold during HUT. AP decreased at the onset of HUT compared with that in the supine position in 15 of 25 subjects without GVS (-12+/-2 mmHg), but applying GVS at 0.1 mA below the somatosensory threshold diminished the decrease (0.3+/-0.7 mmHg). The APs of another 10 subjects were maintained or decreased by less than 5 mmHg without GVS at the onset of HUT (4+/-2 mmHg), but applying GVS at the amplitude of 0.1 mA below the somatosensory threshold further increased the AP (12+/-2 mmHg). GVS at the other amplitudes did not result in AP changes in either group. Thus, subsensory weak GVS enhances AP control at the onset of HUT. PMID- 22088943 TI - alpha2-Adrenergic receptor distribution and density within the nucleus tractus solitarii of normotensive and hypertensive rats during development. AB - The nucleus tractus solitarii (NTS), located in the brainstem, is one of the main nuclei responsible for integrating different signals in order to originate a specific and orchestrated autonomic response. Antihypertensive drugs are well known to stimulate alpha(2)-adrenoceptor (alpha(2R)) in brainstem cardiovascular regions to induce reduction in blood pressure. Because alpha(2R) impairment is present in several models of hypertension, the aim of the present study was to investigate the distribution and density of alpha(2R) binding within the NTS of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats during development (1,15,30 and 90 day-old) by an in vitro autoradiographical study. The NTS shows heterogeneous distribution of alpha(2R) in dorsomedial/dorsolateral, subpostremal and medial/intermediate subnuclei. Alpha(2R) increased from rostral to caudal dorsomedial/dorsolateral subnuclei in 30 and 90 day-old SHR but not in WKY. Alpha(2R) decreased from rostral to caudal subpostremal subnucleus in 15, 30 and 90 day-old SHR but not in WKY. Medial/intermediate subnuclei did not show any changes in alpha(2R) according to NTS levels. Furthermore, alpha(2R) are decreased in SHR as compared with WKY in all NTS subnuclei and in different ages. Surprisingly, alpha(2R) impairment was also found in pre-hypertensive stages, specifically in subpostremal subnucleus of 15 day-old rats. Finally, alpha(2R) decrease from 1 to 90 day-old rats in all subnuclei analyzed. This decrease is different between strains in rostral dorsomedial/dorsolateral and caudal subpostremal subnuclei within the NTS. In summary, our results highlight the importance of alpha(2R) distribution within the NTS regarding the neural control of blood pressure and the development of hypertension. PMID- 22088945 TI - The characterisation of two halogenated cathinone analogues: 3,5 difluoromethcathinone and 3,5-dichloromethcathinone. AB - Australia has seen an increase in the importation and use of drugs that are marketed and sold as "Legal Highs". These compounds have largely tended to be various cathinone analogues, with 4-methylmethcathinone the most prominent to date. In January 2009, unknown samples were submitted for analysis along with a large seizure of 3-fluoromethcathinone as part of a police operation. The samples were analysed and determined to be 3,5-difluoromethcathinone and 3,5 dichloromethcathinone. These compounds were synthesised and characterised. The GC MS data of the samples and their N-acetyl derivatives, NMR, vapour-phase and condensed-phase IR for these previously unreported compounds are presented. This analytical data will enable laboratories to confirm the presence of these compounds in the absence of commercially available reference standards. PMID- 22088944 TI - Trypanosomes and the solution to a 50-year mitochondrial calcium mystery. AB - The ability of mitochondria to take up Ca(2+) was discovered 50 years ago. This calcium uptake, through a mitochondrial calcium uniporter (MCU), is important not only for the regulation of cellular ATP concentration but also for more complex pathways such as shaping Ca(2+) signals and the activation of programmed cell death. The molecular nature of the uniporter remained unknown for decades. By a comparative study of mitochondrial protein profiles of organisms lacking or possessing MCU, such as yeast in the former case and vertebrates and trypanosomes in the latter, two groups recently found the protein that possesses all the characteristics of the MCU. These results add another success story to the already substantial contributions of trypanosomes to mammalian biochemistry. PMID- 22088946 TI - Society of Hair Testing guidelines for drug testing in hair. AB - The Society of Hair Testing (SoHT) Guidelines for Drug Testing in Hair provide laboratories with recommended best practice guidelines whether they are currently offering drug testing in hair, or plan to offer a hair testing service in the future. The guidelines include reference to recommended sample collection and storage procedures, through sample preparation, pre-treatment and analysis and the use of cut-offs. PMID- 22088947 TI - Parameters of arterial stiffness: hypertensive and diabetic patients vs controls. PMID- 22088948 TI - Expanded endonasal approach for the clipping of a ruptured basilar aneurysm and feeding artery to a cerebellar arteriovenous malformation. AB - While endovascular techniques play a significant and expanding role in the management of basilar trunk aneurysms, open surgical clipping remains necessary in select cases. Expanded endonasal transclival approaches offer the advantage of direct access and visualization of the midline vertebrobasilar system, benefits ideally suited to a basilar trunk aneurysm. A 59-year old woman with subarachnoid hemorrhage was found to have a ruptured basilar trunk aneurysm associated with a feeding vessel to a small cerebellar arteriovenous malformation (AVM). An expanded endoscopic endonasal transclival approach was used to successfully clip the basilar trunk aneurysm and feeding AVM vessel. The patient was subsequently discharged home without any neurological deficits. Transclival clipping of basilar trunk aneurysms is technically feasible and plays an important role in management when other strategies fail. The technical benefits of this approach include proximal and distal control of the basilar artery and improved visualization of the brainstem and perforators. Endoscopic transclival approaches should be considered in the management of complex basilar trunk aneurysms. PMID- 22088949 TI - Focal brain atrophy in gastric bypass patients with cognitive complaints. AB - Recently, we have identified a series of patients presenting with cognitive complaints after gastric bypass, without any identifiable etiology. We aimed to determine if focal brain atrophy could account for the complaints. A retrospective case series was performed to identify patients with cognitive complaints following gastric bypass who had a volumetric MRI. Voxel-based morphometry was used to assess patterns of grey matter loss in all 10 patients identified, compared to 10 age and gender-matched controls. All patients had undergone Roux-en-Y gastric bypass surgery at a median age of 54 (range: 46-64). Cognitive complaints developed at a median age of 57 (52-69). Formal neuropsychometric testing revealed only minor deficits. No nutritional abnormalities were identified. Voxel-based morphometry demonstrated focal thalamic atrophy in the gastric bypass patients when compared to controls. Patients with cognitive complaints after gastric bypass surgery may have focal thalamic brain atrophy that could result in cognitive impairment. PMID- 22088950 TI - Diffuse central neurocytoma with craniospinal dissemination. AB - Central neurocytomas (CN) are benign central nervous system (CNS) tumors of neuroglial origin that represent 0.25 to 0.5% of all intracranial tumors in adults and an even smaller proportion of pediatric CNS tumors. These tumors characteristically occur in the subependymal layer of the lateral ventricle near the foramen of Monro and appear as sharply demarcated, solitary lesions. Surgical resection is considered curative, as the reported recurrence rate is less than 5% for patients with localized disease. In this report, we describe the case of a three-year-old boy with a diffuse CN with craniospinal dissemination identified at the time of diagnosis. Given the extensive nature of the disease, surgical resection was not indicated and he underwent a chemotherapeutic regimen of vincristine and carboplatin. At 18 months followup, the patient has completed 6 of 8 total cycles of vincristine and carboplatin and serial imaging shows stable disease within the craniospinal axis. PMID- 22088951 TI - Entrapment of the extensor pollicis longus tendon after a radial fracture in a child. PMID- 22088952 TI - Re: Ozcelik B, Egemen O, Sacak B. How to prevent the avulsed soft tissues from wrapping around the K-wire. J Hand Surg Eur. 2011, 36: 518-9. PMID- 22088953 TI - The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease. AB - Parkinson's disease (PD) is a debilitating neurodegenerative disorder associated with severe motor impairments caused by the loss of dopaminergic innervation of the striatum. Previous studies have demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGlu4), including N phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxamide, can produce antiparkinsonian-like effects in preclinical models of PD. However, these early mGlu4 PAMsexhibited unsuitable physiochemical properties for systemic dosing, requiring intracerebroventricular administration and limiting their broader utility as in vivo tools to further understand the role of mGlu4 in the modulation of basal ganglia function relevant to PD. In the present study, we describe the pharmacologic characterization of a systemically active mGlu4 PAM, N (3-chlorophenyl)picolinamide (VU0364770), in several rodent PD models. VU0364770 showed efficacy alone or when administered in combination with L-DOPA or an adenosine 2A (A2A) receptor antagonist currently in clinical development (preladenant). When administered alone, VU0364770 exhibited efficacy in reversing haloperidol-induced catalepsy, forelimb asymmetry-induced by unilateral 6 hydroxydopamine (6-OHDA) lesions of the median forebrain bundle, and attentional deficits induced by bilateral 6-OHDA nigrostriatal lesions in rats. In addition, VU0364770 enhanced the efficacy of preladenant to reverse haloperidol-induced catalepsy when given in combination. The effects of VU0364770 to reverse forelimb asymmetry were also potentiated when the compound was coadministered with an inactive dose of L-DOPA, suggesting that mGlu4 PAMs may provide L-DOPA-sparing activity. The present findings provide exciting support for the potential role of selective mGlu4 PAMs as a novel approach for the symptomatic treatment of PD and a possible augmentation strategy with either L-DOPA or A2A antagonists. PMID- 22088954 TI - Roscovitine inhibits CaV3.1 (T-type) channels by preferentially affecting closed state inactivation. AB - T-type calcium channels (Ca(V)3) play an important role in many physiological and pathological processes, including cancerogenesis. Ca(V)3 channel blockers have been proposed as potential cancer treatments. Roscovitine, a trisubstituted purine, is a cyclin-dependent kinase (CDK) inhibitor that is currently undergoing phase II clinical trials as an anticancer drug and has been shown to affect calcium and potassium channel activity. Here, we investigate the effect of roscovitine on Ca(V)3.1 channels. Ca(V)3.1 channels were transiently expressed in human embryonic kidney 293 cells, and currents were recorded by using the whole cell patch-clamp technique. Roscovitine blocks Ca(V)3.1 channels with higher affinity for depolarized cells (EC50 of 10 MUM), which is associated with a negative shift in the voltage dependence of closed-state inactivation. Enhanced inactivation is mediated by roscovitine-induced acceleration of closed-state inactivation and slowed recovery from inactivation. Small effects of roscovitine were also observed on T-channel deactivation and open-state inactivation, but neither could explain the inhibitory effect. Roscovitine inhibits Ca(V)3.1 channels within the therapeutic range (10-50 MUM) in part by stabilizing the closed-inactivated state. The ability of roscovitine to block multiple mediators of proliferation, including CDKs and Ca(V)3.1 channels, may facilitate its anticancer properties. PMID- 22088955 TI - Identification of novel molecular scaffolds for the design of MMP-13 inhibitors: a first round of lead optimization. AB - Osteoarthritis (OA) is the leading cause of joint pain and disability in middle aged and elderly patients, and is characterized by progressive loss of articular cartilage. Among the various matrix metalloproteinases (MMPs), MMP-13 is specifically expressed in the cartilage of human OA patients and is not present in normal adult cartilage. Thus, MMP-13-selective inhibitors are promising candidates in osteoarthritis therapy. Recently, we designed an N-isopropoxy arylsulfonamide-based hydroxamate inhibitor, which showed low nanomolar activity and high selectivity for MMP-13. In parallel to further studies aiming to assess the in vivo activity of our compound, we screened the Life Chemicals database through computational docking to seek for novel scaffolds as zinc-chelating non hydroxamate inhibitors. Experimental evaluation of 20 selected candidate compounds verified five novel leads with IC(50) in the low MUM range. These newly discovered inhibitors are structurally unrelated to the ones known so far and provide useful scaffolds to develop compounds with more desirable properties. Finally, a first round of structure-based optimization on lead 1 was accomplished and led to an increase in potency of more than 5 fold. PMID- 22088956 TI - Identification and development of 2,5-disubstituted oxadiazole as potential candidate for treatment of XDR and MDR tuberculosis. AB - Tuberculosis, the infection on the verge of eradication once, is now a great threat to mankind. Emergence of MDR and XDR-TB synergised with HIV and other immune-compressive diseases have increased the life threatening capacities of the disease. A small molecule has been identified here, which showed potent anti tubercular activity. The identified hit compound has also been proved active against nearly 25 clinical isolates comparable with isoniazid. PMID- 22088957 TI - Effect of leachate recirculation on mesophilic anaerobic digestion of food waste. AB - The effects of using untreated leachate for supplemental water addition and liquid recirculation on anaerobic digestion of food waste was evaluated by combining cyclic water recycle operations with batch mesophilic biochemical methane potential (BMP) assays. Cyclic BMP assays indicated that using an appropriate fraction of recycled leachate and fresh make up water can stimulate methanogenic activity and enhance biogas production. Conversely increasing the percentage of recycled leachate in the make up water eventually causes methanogenic inhibition and decrease in the rate of food waste stabilization. The decrease in activity is exacerbated as the number cycles increases. Inhibition is possibly attributed to accumulation and elevated concentrations of ammonia as well as other waste by products in the recycled leachate that inhibit methanogenesis. PMID- 22088958 TI - Assessment of biotechnological strategies for the valorization of metal bearing wastes. AB - The present work deals with the application of biotechnology for the mobilization of metals from different solid wastes: end of life industrial catalysts, heavy metal contaminated marine sediments and fluorescent powders coming from a cathode ray tube glass recycling process. Performed experiments were aimed at assessing the performance of acidophilic chemoautotrophic Fe/S-oxidizing bacteria for such different solid matrices, also focusing on the effect of solid concentration and of different substrata. The achieved results have evidenced that metal solubilization seems to be strongly influenced by the metal speciation and partitioning in the solid matrix. No biological effect was observed for Ni, Zn, As, Cr mobilization from marine sediments (34%, 44%, 15%, 10% yields, respectively) due to metal partitioning. On the other hand, for spent refinery catalysts (Ni, V, Mo extractions of 83%, 90% and 40%, respectively) and fluorescent powders (Zn and Y extraction of 55% and 70%, respectively), the improvement in metal extraction observed in the presence of a microbial activity confirms the key role of Fe/S oxidizing bacteria and ferrous iron. A negative effect of solid concentration was in general observed on bioleaching performances, due to the toxicity of dissolved metals and/or to the solid organic component. PMID- 22088959 TI - Techno-economic evaluation of ultrasound and thermal pretreatments for enhanced anaerobic digestion of municipal waste activated sludge. AB - To enhance the anaerobic digestion of municipal waste-activated sludge (WAS), ultrasound, thermal, and ultrasound+thermal (combined) pretreatments were conducted using three ultrasound specific energy inputs (1000, 5000, and 10,000 kJ/kg TSS) and three thermal pretreatment temperatures (50, 70 and 90 degrees C). Prior to anaerobic digestion, combined pretreatments significantly improved volatile suspended solid (VSS) reduction by 29-38%. The largest increase in methane production (30%) was observed after 30 min of 90 degrees C pretreatment followed by 10,000 kJ/kg TSS ultrasound pretreatment. Combined pretreatments improved the dimethyl sulfide (DMS) removal efficiency by 42-72% but did not show any further improvement in hydrogen sulfide (H(2)S) removal when compared with ultrasound and thermal pretreatments alone. Economic analysis showed that combined pretreatments with 1000 kJ/kg TSS specific energy and differing thermal pretreatments (50-90 degrees C) can reduce operating costs by $44-66/ton dry solid when compared to conventional anaerobic digestion without pretreatments. PMID- 22088960 TI - Different treatment strategies for highly polluted landfill leachate in developing countries. AB - The aim of this research was to determine appropriate treatment technique for effective treatment of heavily polluted landfill leachate. We accomplished several treatment experiments: (i) aerobic biological treatment, (ii) chemical coagulation, (iii) advanced oxidation process (AOP) and (iv) several combined treatment strategies. Efficiency of these treatment procedures were monitored by analysing COD and colour removal. Leachate used for this study was taken from Matuail landfill site at Dhaka city. With extended aeration process which is currently used in Matuail landfill site for leachate treatment, maximum COD and colour removal of 36% and 20%, respectively could be achieved with optimum retention period of 7 days. With optimum aluminium sulphate dose of 15,000 mg/L and pH value of 7.0, maximum COD and colour removals of 34% and 66%, respectively were observed by using chemical coagulation. With optimum pH of 5.0 and optimum dosages of reagents having H(2)O(2)/Fe(2+) molar ratio of 1.3 the highest removal of COD and colour were found 68% and 87%, respectively with sludge production of 55%. Fenton treatment which is an advanced oxidation process was the most successful between these three separate treatment procedures. Among the combined treatment options performed, extended aeration followed by Fenton method was the most suitable one. PMID- 22088961 TI - Anaerobic digestion of chicken feather with swine manure or slaughterhouse sludge for biogas production. AB - Biogas production from anaerobic digestion of chicken feathers with swine manure or slaughterhouse sludge was assessed in two separate experiments. Ground feathers without any pre-treatment were added to 42-L digesters inoculated with swine manure or slaughterhouse sludge, representing 37% and 23% of total solids, respectively and incubated at 25 degrees C in batch mode. Compared to the control without feather addition, total CH(4) production increased by 130% (P<0.001) and 110% (P=0.09) in the swine manure and the slaughterhouse sludge digesters, respectively. Mixed liquor NH(4)N concentration increased (P<0.001) from 4.8 and 3.1g/L at the beginning of the digestion to 6.9 and 3.5 g/L at the end of digestion in the swine manure and the slaughterhouse sludge digesters, respectively. The fraction of proteolytic microorganisms increased (P<0.001) during the digestion from 12.5% to 14.5% and 11.3% to 13.0% in the swine manure and the slaughterhouse sludge digesters with feather addition, respectively, but decreased in the controls. These results are reflective of feather digestion. Feather addition did not affect CH(4) yields of the swine manure digesters (P=0.082) and the slaughterhouse sludge digesters (P=0.21), indicating that feathers can be digested together with swine manure or slaughterhouse sludge without negatively affecting the digestion of swine manure and slaughterhouse sludge. PMID- 22088962 TI - Bias correction in the hierarchical likelihood approach to the analysis of multivariate survival data. AB - Frailty models are useful for measuring unobserved heterogeneity in risk of failures across clusters, providing cluster-specific risk prediction. In a frailty model, the latent frailties shared by members within a cluster are assumed to act multiplicatively on the hazard function. In order to obtain parameter and frailty variate estimates, we consider the hierarchical likelihood (H-likelihood) approach (Ha, Lee and Song, 2001. Hierarchical-likelihood approach for frailty models. Biometrika 88, 233-243) in which the latent frailties are treated as "parameters" and estimated jointly with other parameters of interest. We find that the H-likelihood estimators perform well when the censoring rate is low, however, they are substantially biased when the censoring rate is moderate to high. In this paper, we propose a simple and easy-to-implement bias correction method for the H-likelihood estimators under a shared frailty model. We also extend the method to a multivariate frailty model, which incorporates complex dependence structure within clusters. We conduct an extensive simulation study and show that the proposed approach performs very well for censoring rates as high as 80%. We also illustrate the method with a breast cancer data set. Since the H-likelihood is the same as the penalized likelihood function, the proposed bias correction method is also applicable to the penalized likelihood estimators. PMID- 22088963 TI - Arousal modulates temporal preparation under increased time uncertainty: Evidence from higher-order sequential foreperiod effects. AB - When the foreperiod (FP) is unpredictably varied in reaction-time tasks, responses are slow at short but fast at long FPs (variable-FP effect), and further vary asymmetrically as a function of FP sequence (sequential FP effect). A trace-conditioning model attributes these phenomena to time-related associative learning, while a dual-process model views them as resulting from combined effects of strategic preparation and trial-to-trial changes in arousal. Sometimes, responses are slower in long-long than in short-long FP sequences. This pattern is not predicted from the trace-conditioning account, since FP repetitions should speed up, rather than slow down, responses (due to reinforcement). The effect, however, might indicate the contribution of arousal, which according to the dual-process model, is heightened after a short FP(n-1) but decreased after a long FP(n-1). In five experiments, we examined higher-order sequential FP effects on performance, with a particular emphasis on analyzing performance in long-FP(n) trials as a function of FP length in the two preceding trials, varying temporal FP context (i.e. average FP length) and reaction mode (simple vs. choice reaction). Slower responses in long-long-long (compared with short-short-long) FP sequences were not found within a short-FP context (Exps. 1 & 2) but clearly emerged within a long-FP context (Exps. 3-5). This pattern supports the notion that transient arousal changes contribute to sequential performance effects in variable-FP tasks, in line with the dual-process account of temporal preparation. PMID- 22088964 TI - Diversity of human leukemia xenograft mouse models: implications for disease biology. AB - Over the past decade, xenografting human leukemia cells into mice with different levels of immunodeficiency, with or without preconditioning, has provided an important tool to study various aspects of leukemia biology and to identify distinct clinical risk groups for evaluation of novel therapeutic strategies, as well as the possibility of amplifying human leukemia cells in vivo. Interestingly, these models using human acute lymphoblastic leukemia and acute myeloid leukemia cells as xenografts recapitulate many clinical features of the disease. Similar to the human environment (for example, in the bone marrow), transplanted leukemia cells in the murine setting are exposed to both favorable and unfavorable conditions for engraftment that may exert a distinct pressure for selection of subclones. Thus, results obtained in these models may vary depending on the experimental setup. The impact of in vivo growth of human leukemia cells on the background of a more or less hostile murine environment for leukemia biology and the course of the disease in patients are discussed in the context of the diversity of xenograft models. PMID- 22088965 TI - Identification of tumorigenic cells in Kras(G12D)-induced lung adenocarcinoma. AB - We established an inducible Kras(G12D)-driven lung adenocarcinoma in CCSP rtTA/TetO-Cre/LSL-Kras(G12D) mice that enable pursuits of the cellular and molecular processes involved in Kras-induced tumorigenesis. To investigate the cellular origin of this cancer, we first report a strategy using fluorescence activated cell sorting fractionation that could highly enrich bronchiolar Clara and alveolar type II cells, respectively. The EpCAM(+)MHCII(-) cells (bronchiolar origin) were more enriched with tumorigenic cells in generating secondary tumors than EpCAM(+)MHCII(+) cells (alveolar origin) in primary tumors that had been already initiated with oncogenic Kras activation. In addition, secondary tumors derived from EpCAM(+)MHCII(-) cells showed diversity of tumor locations compared with those derived from EpCAM(+)MHCII(+) cells. In the alveolar region, secondary tumors from EpCAM(+)MHCII(-) cells expressed not only bronchiolar epithelial marker, panCK, but also differentiation marker, proSPC, consistent with the notion that cancer-initiating cells display not only the abilities for self renewal but also the features of differentiation to generate heterogeneous tumors with phenotypic diversity. Furthermore, high level of ERK1/2 activation and colony-forming ability as well as lack of Sprouty-2 expression were also observed in EpCAM(+)MHCII(-) cells. Therefore, these results suggest that bronchiolar Clara cells are the origin of cells and tumorigenesis for Kras(G12D)-induced neoplasia in the lungs. PMID- 22088966 TI - Effect of fruit and vegetable intake on oxidative stress and inflammation in COPD: a randomised controlled trial. AB - Epidemiological evidence supports a positive relationship between fruit and vegetable (FV) intake, lung function and chronic obstructive pulmonary disease (COPD). Increasing FV intake may attenuate the oxidative stress and inflammation associated with COPD. An exploratory randomised controlled trial to examine the effect of increased consumption of FV on oxidative stress and inflammation in moderate-to-severe COPD was conducted. 81 symptomatically stable patients with a habitually low FV intake (two or fewer portions of FV per day) were randomised to the intervention group (five or more portions of FV per day) or the control group (two or fewer portions of FV per day). Each participant received self-selected weekly home deliveries of FV for 12 weeks. 75 participants completed the intervention. There was a significant between-group change in self-reported FV intake and biomarkers of FV intake (zeaxanthin (p = 0.034) and beta-cryptoxanthin (p = 0.015)), indicating good compliance; post-intervention intakes in intervention and control groups were 6.1 and 1.9 portions of FV per day, respectively. There were no significant changes in biomarkers of airway inflammation (interleukin-8 and myeloperoxidase) and systemic inflammation (C reactive protein) or airway and systemic oxidative stress (8-isoprostane). This exploratory study demonstrated that patients with moderate-to-severe COPD were able to comply with an intervention to increase FV intake; however, this had no significant effect on airway or systemic oxidative stress and inflammation. PMID- 22088967 TI - Community-acquired pneumonia in younger patients is an entity on its own. AB - Community-acquired pneumonia (CAP) is now most frequent in elderly patients. CAP in the younger patient has attracted much less attention. Therefore, we compared patients with CAP aged 18 to <65 yrs with those aged >= 65 yrs. Data from the prospective multicentre Competence Network for Community Acquired Pneumonia Study Group (CAPNETZ) database were analysed for potential differences in baseline characteristics, comorbidities, clinical presentation, microbial investigations, aetiologies, antimicrobial treatment and outcomes. Overall, 7,803 patients were studied. The proportion of younger patients (aged <65 yrs) was 52.3% (18 to <30 yrs 6.4%; <40 yrs 17.1%; <50 yrs 29.4%). Comorbidity was present in only half of the younger patients (46.6% versus 88.2%). Fever and chest pain were more common. Most younger patients presented with mild CAP (74.0% had a CRB-65 [corrected] score of 0 (confusion of new onset, [corrected] respiratory rate of >= 30 breaths . min(-1), blood pressure <90 mmHg or diastolic blood pressure <= 60 mmHg, age >= 65 yrs)). Overall, Streptococcus pneumoniae and Mycoplasma pneumoniae were the most frequent pathogens in the younger patients. Short-term mortality was very low (1.7% versus 8.2%) and even lower in patients without comorbidity (0.3% versus 2.4%). Long-term mortality was 3.2% versus 15.9%, also lower in patients without comorbidity (0.8% versus 6.1%). Most of the differences found clearly arise after the fifth or within the middle of the sixth decade. CAP in the younger patient is a clinically distinct entity. PMID- 22088968 TI - CXCR1 and CXCR2 haplotypes synergistically modulate cystic fibrosis lung disease. AB - Cystic fibrosis (CF) lung disease severity is largely independent on the CF transmembrane conductance regulator (CFTR) genotype, indicating the contribution of genetic modifiers. The chemokine receptors CXCR1 and CXCR2 have been found to play essential roles in the pathogenesis of CF lung disease. Here, we determine whether genetic variation of CXCR1 and CXCR2 influences CF lung disease severity. Genomic DNA of CF patients in Germany (n = 442) was analysed for common variations in CXCR1 and CXCR2 using a single-nucleotide polymorphism (SNP) tagging approach. Associations of CXCR1 and CXCR2 SNPs and haplotypes with CF lung disease severity, CXCR1 and CXCR2 expression, and neutrophil effector functions were assessed. Four SNPs in CXCR1 and three in CXCR2 strongly correlated with age-adjusted lung function in CF patients. SNPs comprising haplotypes CXCR1_Ha and CXCR2_Ha were in high linkage disequilibrium and patients heterozygous for the CXCR1-2 haplotype cluster (CXCR1-2_Ha) had lower lung function compared with patients with homozygous wild-type alleles (forced expiratory volume in 1 s <= 70% predicted, OR 7.24; p = 2.30 * 10(-5)). CF patients carrying CXCR1-2_Ha showed decreased CXCR1 combined with increased CXCR2 mRNA and protein expression, and displayed disturbed antibacterial effector functions. CXCR1 and CXCR2 genotypes modulate lung function and antibacterial host defence in CF lung disease. PMID- 22088969 TI - Ventilation/perfusion lung scan in pulmonary veno-occlusive disease. AB - Pulmonary veno-occlusive disease (PVOD), a rare form of pulmonary arterial hypertension (PAH), requires histological proof for definitive diagnosis; however, lung biopsy is not recommended in PAH. Recent conjoint European Respiratory Society/European Society of Cardiology guidelines suggest that nonmatched perfusion defects on ventilation/perfusion (V'/Q') lung scanning in PAH patients may suggest PVOD. The aim of our study was to evaluate V'/Q' lung scans in a large cohort of PVOD and idiopathic or heritable PAH patients. V'/Q' lung scans from 70 patients with idiopathic or heritable PAH and 56 patients with confirmed or highly probable PVOD were reviewed in a double-blind manner. The vast majority of V'/Q' lung scans were normal or without significant abnormalities in both groups. No differences in ventilation or perfusion lung scans were observed between PAH and PVOD patients (all p>0.05). Furthermore, no differences were observed between confirmed (n=31) or highly probable PVOD (n=25). Nonmatched perfusion defects were found in seven (10%) idiopathic PAH patients and four (7.1%) PVOD patients (p>0.05). Nonmatched perfusion defects were rarely seen in a large cohort of idiopathic or heritable PAH and PVOD patients. Future recommendations should be amended according to these results suggesting that V'/Q' lung scanning is not useful in discriminating PVOD from idiopathic PAH. PMID- 22088970 TI - Early detection of COPD is important for lung cancer surveillance. AB - It is well known that chronic obstructive pulmonary disease (COPD) is a significant risk factor for lung cancer. Approximately 1% of COPD patients develop lung cancer every year, which may be associated with genetic susceptibility to cigarette smoke. Chronic inflammation caused by toxic gases can induce COPD and lung cancer. Inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of nuclear factor-kappaB and signal transducer and activator of transcription 3 play crucial roles in the development of lung cancer from COPD. Low-dose computed tomography (LDCT) is an effective procedure for the early detection of lung cancer in high-risk patients. However, determining which patients should be screened for lung cancer in a primary care setting is difficult. In this article, we review the epidemiology and aetiology of lung cancer associated with COPD, verify the efficacy of lung cancer screening by LDCT, and discuss the importance of early detection of COPD for lung cancer surveillance. We propose that, for the prevention of both diseases, COPD screening in smokers should be initiated as early as possible, so they can stop smoking and so that candidates for an efficient lung cancer screening programme can be identified. PMID- 22088971 TI - Lack of involvement of type 7 phosphodiesterase in an experimental model of asthma. AB - Type 7 phosphodiesterases (PDE7) are responsible for the decrease of intracellular cyclic AMP (cAMP) in many cells involved in allergic asthma by suppressing their potential to respond to many activating stimuli. The elevation of intracellular cAMP has been associated with immunosuppressive and anti inflammatory activities and represents a potential treatment of asthma. Our aim was to evaluate the impact of the deletion of the murine phosphodiesterase (PDE)7B gene and then to evaluate the efficacy of a newly described selective PDE7A and -B inhibitor on an ovalbumin (OVA)-induced airway inflammation and airway hyperreactivity (AHR) model in mice. Inflammation was determined 72 h after single OVA challenge or 24 h after multiple challenges by the relative cell influx and cytokine content in bronchoalveolar lavage fluid. AHR and immunoglobulin E levels in serum were determined after multiple challenges. For the first time, we have demonstrated that the deletion of the PDE7B gene or the pharmacological inhibition of PDE7A and -B had no effect on all the parameters looked at in this model. These results highlight the absence of any implication of the PDE7 enzyme in our model. PMID- 22088972 TI - A role for the CXCL12 receptor, CXCR7, in the pathogenesis of human pulmonary vascular disease. AB - Given the critical role that endothelial cell dysfunction plays in the pathogenesis of pulmonary hypertensive diseases, we set out to establish if CXCR7, a receptor for the pro-angiogenic ligand CXCL12, is expressed in the vasculature of human lung diseases and examine its role in mediating CXCL12 induced responses in primary pulmonary human microvascular endothelial cells. Receptor and ligand expression was examined in control and explanted human hypertensive lungs, in human plasma and in hypoxic rodent lungs, by ELISA and immunohistochemical studies. Functional in vitro experiments examined the role of CXCR7 in CXCL12-induced lung microvascular endothelial cell proliferation, migration, and wound regeneration and repair. CXCR7 is elevated in the endothelium of explanted human hypertensive lungs and circulating CXCL12 concentrations are significantly elevated in disease. We demonstrate that alveolar hypoxia similar to that found in lung disease increases CXCR7 expression in the pulmonary endothelium. Furthermore, CXCR7 is the receptor through which endothelial cell regeneration and repair, and proliferation, is mediated, whereas signalling via CXCR4 is essential for chemotactic cell migration. Our findings demonstrate that CXCR7 has a critical but previously unrecognised role to play in endothelial cell proliferation, suggesting that CXCR7-mediated signalling may be functionally important in pulmonary vascular diseases. PMID- 22088973 TI - Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: a population-based study. AB - Bangladesh has high well water arsenic exposure. Chronic arsenic ingestion may result in diseases that manifest as dyspnoea, although information is sparse. Baseline values were obtained from an arsenic study. Trained physicians ascertained data on dyspnoea among 11,746 subjects. Data were collected on demographic factors, including smoking, blood pressure and arsenic exposure. Logistic regression models estimated odds ratios and confidence intervals for the association between arsenic exposure and dyspnoea. The adjusted odds of having dyspnoea was 1.32-fold (95% CI 1.15-1.52) greater in those exposed to high well water arsenic concentrations (>= 50 MUg . L(-1)) compared with low-arsenic exposed nonsmokers (p<0.01). A significant dose-response relationship was found for arsenic (as well as smoking) in relation to dyspnoea. In nonsmokers, the adjusted odds of having dyspnoea were 1.36, 1.96, 2.34 and 1.80-fold greater for arsenic concentrations of 7-38, 39-90, 91-178 and 179-864 MUg . L(-1), respectively, compared with the reference arsenic concentration of <7 MUg . L(-1) (p<0.01; Chi-squared test for trend). Arsenic exposure through well water is associated with dyspnoea, independently of smoking status. This study suggests that mandated well water testing for arsenic with reduction in exposure may significantly reduce diseases that manifest as dyspnoea, usually cardiac or pulmonary. PMID- 22088974 TI - Mean platelet volume as an indicator of disease severity in patients with acute pancreatitis. AB - AIM: Acute pancreatitis (AP) constitutes a systemic inflammatory process which is often accompanied by thrombosis and bleeding disorders. The role of platelets in the pathophysiology of the disease has not been elucidated yet. Mean platelet volume (MPV) is an index of platelet activation and reported to be influenced by inflammation. The objective of the present study is to assess whether platelet volume would be useful in predicting disease severity in AP. Additionally possible relationship of MPV with clinical and radiologic parameters in conjunction with other inflammatory markers during AP was also investigated. PATIENTS AND METHODS: A total of 144 AP patients (male/female: 87/57), and 40 healthy subjects (male/female: 23/17) were enrolled in this study. Mean platelet volume and inflammatory parameters were measured for all study participants. Modified Glasgow Prognostic Score (mGPS) and the computerized tomography severity index (CTSI) were used as to predict the disease severity in AP patients. RESULTS: A statistically significant decrease in MPV levels was observed in AP patients (8.06 +/- 0.71 fL) compared with healthy controls (8.63 +/- 0.62 fL) (P<0.001). According to the mGPS, overall accuracy of MPV in determining severe AP was 72.7% with a sensitivity, specificity, NPV and PPV of 70.6%, 73.9%, 81.9%, and 60 respectively (AUC: 0.762). Overall accuracy of MPV in predicting disease severity according to CTSI was not superior compared with other inflammation markers. CONCLUSION: The present study demonstrated that MPV is decreased in AP. Assessment of MPV with other inflammatory markers may provide additional information about disease severity in AP. PMID- 22088975 TI - Development and application of a method for the analysis of two trichothecenes: deoxynivalenol and T-2 toxin in meat in China by HPLC-MS/MS. AB - A reliable and sensitive method was developed and successfully applied for the determination of deoxynivalenol and T-2 toxin simultaneously in pig dorsal muscle, pig back fat and chicken muscle by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) analysis. Limit of detection of deoxynivalenol and T-2 was 0.02MUg/kg and 0.007MUg/kg, and limit of quantification of deoxynivalenol and T-2 was 0.07MUg/kg and 0.02MUg/kg, respectively. Sixty-six meat samples were analyzed and deoxynivalenol was detected in the samples of pig back fat, with concentrations lower than 0.5MUg/kg, and T-2 toxin was detected in the samples of pig dorsal muscle, pig back fat and chicken muscle, with concentrations lower than 0.5MUg/kg. The results of sample analysis show that only trace residues of deoxynivalenol and T 2 toxin were detected in the samples analyzed. PMID- 22088976 TI - Investigation of the insulin-like properties of zinc(II) complexes of 3-hydroxy-4 pyridinones: identification of a compound with glucose lowering effect in STZ induced type I diabetic animals. AB - Results from an investigation in an in vivo model of STZ-induced diabetic rats demonstrate that compound bis(1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate)zinc(II), Zn(dmpp)(2), significantly lowers the blood glucose levels of individuals, thus showing evidence of glucose lowering activity. The compound was selected from a set of eight zinc(II) complexes of 3-hydroxy-4-pyridinones with diverse lipophilicity that were prepared and characterized in our laboratory. Assessment of insulin-like activity of the complexes was firstly performed in vitro by measuring the inhibition of FFA release in isolated rat adipocytes. The results indicate that compounds bis(2-methyl-3-hydroxy-4-pyridinonate)zinc(II), Zn(mpp)(2) and Zn(dmpp)(2) display significantly higher activity than that of the respective positive control thus suggesting its selection for in vivo tests. Safety evaluation of the active zinc(II) compounds was performed in freshly isolated rat hepatocytes. The results support that cell viability is not significantly different from the control set after 1 and 2h of incubation with both zinc(II) complexes. PMID- 22088977 TI - Individual doses for women undergoing screening mammography examinations in Poland in 2007. AB - Exposure doses to women undergoing screening mammography examinations should be kept as low as reasonably achievable, but they should ensure high enough image quality for adequate diagnosis. The aim of this study was to estimate the radiation risk according to the 'European guidelines for quality assurance in breast cancer screening and diagnosis', fourth edition (European Commission 2006). Materials for this study were obtained from data from 250 screening mammography facilities in Poland. For every mammography facility, a standard average glandular dose for routine exposure was calculated. Furthermore, average glandular doses for individual mammography examinations obtained according to the methods proposed by Dance et al (2000 Phys. Med. Biol. 45 3225-40) were calculated. The average glandular doses determined for 250 mammography facilities ranged from 0.12 to 14.56 mGy (the mean values ranged from 0.62 to 4.53 mGy). Only for 39 mammography facilities were all exposures found to be below the acceptable level for an average glandular dose, and for only 18 mammography facilities did no exposures exceed the achievable levels for an average glandular dose. Average glandular doses to women undergoing mammography screening attained unnecessary high values, and they were found to depend on the technical parameters of the mammography equipment and maintenance of mammography units by personnel in various mammography facilities. PMID- 22088978 TI - A novel approach for the synthesis of superparamagnetic Mn3O4 nanocrystals by ultrasonic bath. AB - In this study, the synthesis of Mn(3)O(4) (husmannite) nanoparticles was carried out in two different alkali media under sonication by ultrasonic bath and conventional method. Manganese acetate was used as precursor, sodium hydroxide and hexamethylenetetramine (HMT) as basic reagents in this synthesis. An ultrasonic bath with low intensity was used for the preparation of nanomaterials. The as prepared samples were characterized with X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (HRTEM, TEM), energy-dispersive spectrum (EDS), and superconducting quantum interference device (SQUID) analysis. The XRD patterns exhibit the nanocrystals are in pure tetragonal phase. The chemical composition was obtained by EDS analysis and confirmed the presence of Mn and O in the sample. According to the TEM and HRTEM results, both nanorods and nanoparticles of Mn(3)O(4) were obtained in the presence of ultrasonic irradiation. The average size of nanoparticles was 10nm, and the size of nanorods was 12 nm in diameter and 100-900 nm in length for the samples prepared in basic medium with sodium hydroxide. In the conventional method with the same basic medium, the nanorod was not observed and the nearly cubic nanoparticles was appeared with an average size of 2.5 nm. The selected area electron diffraction (SAED) patterns revealed that the nanocrystals are polycrystalline in nature. When HMT was used as a basic reagent in the presence of ultrasonic irradiation, it was led to a higher size of nanoparticles and nanorods than when sodium hydroxide was used as a basic reagent. The average size of nanoparticles was about 15 nm and its shape was nearly cubic. The diameter for nanorods was 50 nm and the length was about a few micrometers. The magnetic measurements were carried out on the sample prepared in sodium hydroxide under ultrasonic irradiation. These measurements as a function of temperature and field strength showed a reduction in ferrimagnetic temperature (T(c) = 40K) as compared to those reported for the bulk (T(c) = 43K). The superparamagnetic behavior was observed at room temperature with no saturation magnetization and hysteresis in the region of measured field strength. PMID- 22088980 TI - Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. AB - CONTEXT: Variants in the CYP2C19 gene influence the pharmacologic and clinical response to the standard 75-mg daily maintenance dose of the antiplatelet drug clopidogrel. OBJECTIVE: To test whether higher doses (up to 300 mg daily) improve the response to clopidogrel in the setting of loss-of-function CYP2C19 genotypes. DESIGN, SETTING, AND PATIENTS: ELEVATE-TIMI 56 was a multicenter, randomized, double-blind trial that enrolled and genotyped 333 patients with cardiovascular disease across 32 sites from October 2010 until September 2011. INTERVENTIONS: Maintenance doses of clopidogrel for 4 treatment periods, each lasting approximately 14 days, based on genotype. In total, 247 noncarriers of a CYP2C19*2 loss-of-function allele were to receive 75 and 150 mg daily of clopidogrel (2 periods each), whereas 86 carriers (80 heterozygotes, 6 homozygotes) were to receive 75, 150, 225, and 300 mg daily. MAIN OUTCOME MEASURES: Platelet function test results (vasodilator-stimulated phosphoprotein [VASP] phosphorylation and VerifyNow P2Y(12) assays) and adverse events. RESULTS: With 75 mg daily, CYP2C19*2 heterozygotes had significantly higher on-treatment platelet reactivity than did noncarriers (VASP platelet reactivity index [PRI]: mean, 70.0%; 95% CI, 66.0%-74.0%, vs 57.5%; 95% CI, 55.1%-59.9%, and VerifyNow P2Y(12) reaction units [PRU]: mean, 225.6; 95% CI, 207.7-243.4, vs 163.6; 95% CI, 154.4-173.9; P < .001 for both comparisons). Among CYP2C19*2 heterozygotes, doses up to 300 mg daily significantly reduced platelet reactivity, with VASP PRI decreasing to 48.9% (95% CI, 44.6%-53.2%) and PRU to 127.5 (95% CI, 109.9-145.2) (P < .001 for trend across doses for both). Whereas 52% of CYP2C19*2 heterozygotes were nonresponders (>=230 PRU) with 75 mg of clopidogrel, only 10% were nonresponders with 225 or 300 mg (P < .001 for both). Clopidogrel, 225 mg daily, reduced platelet reactivity in CYP2C19*2 heterozygotes to levels achieved with standard clopidogrel, 75 mg, in noncarriers (mean ratios of platelet reactivity, VASP PRI, 0.92; 90% CI, 0.85-0.99, and PRU, 0.94; 90% CI, 0.84-1.04). In CYP2C19*2 homozygotes, even with 300 mg daily of clopidogrel, mean VASP PRI was 68.3% (95% CI, 44.9%-91.6%) and mean PRU, 287.0 (95% CI, 170.2-403.8). CONCLUSION: Among patients with stable cardiovascular disease, tripling the maintenance dose of clopidogrel to 225 mg daily in CYP2C19*2 heterozygotes achieved levels of platelet reactivity similar to that seen with the standard 75 mg dose in noncarriers; in contrast, for CYP2C19*2 homozygotes, doses as high as 300 mg daily did not result in comparable degrees of platelet inhibition. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01235351. PMID- 22088981 TI - The role of progesterone in traumatic brain injury. PMID- 22088979 TI - Racial variation in the cancer caregiving experience: a multisite study of colorectal and lung cancer caregivers. AB - BACKGROUND: As cancer care shifts from hospital to outpatient settings, the number of cancer caregivers continues to grow. However, little is known about the cancer caregiving experience. This gap in knowledge is especially evident for racially diverse caregivers. OBJECTIVE: This study, part of a multisite study of care recipients with either lung or colorectal cancer and their caregivers, examined the caregiving experiences of African American (AA) and white caregivers. METHODS: Caregivers were identified by cancer patients in the Cancer Care Outcomes Research and Surveillance consortium. Caregivers completed a self administered, mailed questionnaire that assessed their characteristics and experiences. Analysis of covariance was used to compare racial groups by objective burden and caregiving resources while controlling for covariates. RESULTS: Despite greater preparedness for the caregiving role (P = .006), AA caregivers reported more weekly hours caregiving than whites did (26.5 +/- 3.1 vs 18.0 +/- 1.7; P = .01). In later phases of caregiving, AAs reported having more social support (P = .02), spending more hours caregiving (31.9 +/- 3.5 vs 16.9 +/ 1.9; P < .001), and performing more instrumental activities of daily living on behalf of their care recipient (P = .021). CONCLUSION: Racial differences in the caregiving experience exist. IMPLICATIONS FOR PRACTICE: Nurses play a key role in educating cancer patients and their caregivers on how to effectively cope with and manage cancer. Because AA caregivers seem to spend more time in the caregiving role and perform more caregiving tasks, AA caregivers may benefit from interventions tailored to their specific caregiving experience. PMID- 22088982 TI - Electron microscopy visualization of DNA-protein complexes formed by Ku and DNA ligase IV. AB - The repair of DNA double-stranded breaks (DSBs) is essential for cell viability and genome stability. Aberrant repair of DSBs has been linked with cancer predisposition and aging. During the repair of DSBs by non-homologous end joining (NHEJ), DNA ends are brought together, processed and then joined. In eukaryotes, this repair pathway is initiated by the binding of the ring-shaped Ku heterodimer and completed by DNA ligase IV. The DNA ligase IV complex, DNA ligase IV/XRRC4 in humans and Dnl4/Lif1 in yeast, is recruited to DNA ends in vitro and in vivo by an interaction with Ku and, in yeast, Dnl4/Lif1 stabilizes the binding of yKu to in vivo DSBs. Here we have analyzed the interactions of these functionally conserved eukaryotic NHEJ factors with DNA by electron microscopy. As expected, the ring-shaped Ku complex bound stably and specifically to DNA ends at physiological salt concentrations. At a ratio of 1 Ku molecule per DNA end, the majority of DNA ends were occupied by a single Ku complex with no significant formation of linear DNA multimers or circular loops. Both Dnl4/Lif1 and DNA ligase IV/XRCC4 formed complexes with Ku-bound DNA ends, resulting in intra- and intermolecular DNA end bridging, even with non-ligatable DNA ends. Together, these studies, which provide the first visualization of the conserved complex formed by Ku and DNA ligase IV at juxtaposed DNA ends by electron microscopy, suggest that the DNA ligase IV complex mediates end-bridging by engaging two Ku bound DNA ends. PMID- 22088983 TI - The effect of nicotine on anti-vascular endothelial growth factor therapy in a mouse model of neovascular age-related macular degeneration. AB - PURPOSE: The purpose of this article is to evaluate the effect of nicotine on anti-vascular endothelial growth factor therapy in the treatment of neovascular age-related macular degeneration. METHODS: One group of mice received nicotine in drinking water and the other group received water only. Choroidal neovascularization (CNV) was induced with a laser. Nicotinic acetylcholine receptor-alpha7 (nAChRalpha7) expression was evaluated by immunohistochemistry. Bevacizumab or adiponectin peptide II (APNpII) was injected intravitreally on Day 7 postlaser, and the effects were evaluated on Days 14 and 21. alpha-Bungarotoxin was injected intraperitoneally on Days 2 to 5, and its effect was evaluated on Day 14. RESULTS: Expression of nAChRalpha7 was 2 to 7 times higher between Days 3 and 7 postlaser compared with naive mice. In water-fed mice, APNpII, bevacizumab, and alpha-bungarotoxin significantly reduced CNV size. In nicotine-fed mice, treatment with APNpII or bevacizumab did not significantly reduce CNV size, whereas alpha-bungarotoxin did have an effect. Comparing water- and nicotine-fed mice, CNV size was 61% to 86% smaller in water-fed mice except for the alpha bungarotoxin group, where there was no difference. Platelet-derived growth factor and vascular endothelial growth factor expression was 1.5- to 2.5-fold higher at Day 14 in nicotine-treated mice. CONCLUSION: Nicotine significantly blocks the effect of anti-vascular endothelial growth factor therapy in the treatment of laser-induced neovascular age-related macular degeneration. nAChRalpha7 is significantly upregulated during the formation of CNV, and treatment with an nAChRalpha7 antagonist decreases CNV size irrespective of nicotine administration. PMID- 22088987 TI - Random Survival Forests. PMID- 22088986 TI - Assessing patient accrual to cooperative group lung cancer trials: why are rates disappointing? PMID- 22088988 TI - The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. AB - INTRODUCTION: The functions of large noncoding RNAs (ncRNAs) have remained elusive in many cases. Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1 (MALAT-1) is an ncRNA that is highly expressed in several tumor types. METHODS: Overexpression and RNA interference (RNAi) approaches were used for the analysis of the biological functions of MALAT-1 RNA. Tumor growth was studied in nude mice. For prognostic analysis, MALAT-1 RNA was detected on paraffin-embedded non small cell lung cancer (NSCLC) tissue probes (n = 352) using in situ hybridization. RESULTS: MALAT-1 was highly expressed in several human NSCLC cell lines. MALAT-1 expression was regulated by an endogenous negative feedback loop. In A549 NSCLCs, RNAi-mediated suppression of MALAT-1 RNA suppressed migration and clonogenic growth. Forced expression of MALAT-1 in NIH 3T3 cells significantly increased migration. Upon injection into nude mice, NSCLC xenografts with decreased MALAT-1 expression were impaired in tumor formation and growth. In situ hybridization on paraffin-embedded lung cancer tissue probes revealed that high MALAT-1 RNA expression in squamous cell carcinoma of the lung was associated with a poor prognosis. On genetic level, MALAT-1 displays the strongest association with genes involved in cancer like cellular growth, movement, proliferation, signaling, and immune regulation. CONCLUSIONS: These data indicate that MALAT-1 expression levels are associated with patient survival and identify tumor promoting functions of MALAT-1. PMID- 22088990 TI - Percutaneous balloon pericardiotomy for recurrent malignant pericardial effusion. PMID- 22088989 TI - Asymptomatic profound sinus bradycardia (heart rate <=45) in non-small cell lung cancer patients treated with crizotinib. AB - Crizotinib, a dual MET/ALK inhibitor, is now in advanced clinical development for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We have observed several patients who developed profound but asymptomatic sinus bradycardia (HR <=45) during the course of crizotinib treatment. Herein, we describe the clinical characteristics of three separate patients enrolled in the A8081001 trial (NCT00585195) who developed asymptomatic profound sinus bradycardia with their accompanying electrocardiogram tracings. PMID- 22088991 TI - Erlotinib in metastatic bronchopulmonary mucoepidermoid carcinoma. PMID- 22088992 TI - The role of postoperative radiotherapy after resection of stage III thymoma. PMID- 22088994 TI - A practical guide to measure "all" malignant pleural mesothelioma tumors by modified RECIST criteria? PMID- 22088996 TI - How should we use bevacizumab in patients with non-small cell lung cancer? PMID- 22088997 TI - Techniques of surgery and radiotherapy for multimodal treatment of pleural mesothelioma. PMID- 22088998 TI - Effectiveness of the single-shot dual-energy subtraction technique for portal images. AB - The aim of the present study was to evaluate the clinical efficacy of the single shot dual-energy subtraction technique for obtaining portal images. We prepared two storage phosphor plates for this study. A 1 mm thick tungsten sheet was placed between the two storage phosphor plates. A single use of the double exposure technique provides two portal images simultaneously (i.e., a standard image and a low-contrast image), using the same patient position and with no additional radiation delivered to the patient. A bone-enhanced image is created by image subtraction between these two images. For evaluation of clinical efficacy, three treatment sites--the brain, lung, and pelvis--were imaged. Ten sets of images were obtained for each site, and five landmarks were selected for each treatment site. The visibility of each landmark and the ease of overall verification for the selected treatment sites were assessed separately for the standard and bone-enhanced images. Four observers consisting of one radiation oncologist and three radiation therapists participated in the present study. For most of the landmarks studied, the bone-enhanced images were significantly superior to the standard images. Regarding the ease of overall verification, the bone-enhanced images were significantly superior to the standard images at all sites. The p-values of mean rating for the brain, lung, and pelvis were 0.002, 0.012, and 0.003, respectively. The bone-enhanced images obtained using our technique increased the image quality in terms of bone visibility, and are considered useful for routine clinical practice. PMID- 22089000 TI - Commissioning of Varian ring & tandem HDR applicators: reproducibility and interobserver variability of dwell position offsets. AB - Studies have shown that source dwells within Varian's HDR CT/MR compatible ring applicators can deviate from intended positions by several millimeters. Quantifying this offset is an important part of commissioning. The aims of this study were to: 1) determine the reproducibility of the offset, 2) study the interobserver variation in the offset's measurement, and 3) quantify the dosimetric impact of the offset. Offsets were measured for four ring applicators: two 30 degrees , one 45 degrees , and one 60 degrees . Dwell positions were measured five times for each ring to determine the reproducibility of source positioning. Experiments were done to compare two separate source wires, as well as different time points within a single source wire's lifecycle. Data were analyzed by three independent observers. To quantify the dosimetric impact of the offset, a treatment plan was generated using BrachyVision. The dose to point A, and the D(2cc) metric for rectum and bladder were calculated with and without the offset. For the 45 degrees and 60 degrees rings, measured offsets were 3.0 mm and 3.6 mm, respectively. The 30 degrees ring showed substantial variation in distal dwell positions (maximum difference between the five experiments of 2.9 mm). Subsequent testing of a replacement ring showed an offset of 2.4 mm that was more reproducible. Offsets varied less than 1 mm between different source wires, and changed less than 1 mm over the course of a source wire's lifecycle. When comparing observers, the average range in a measurement of a dwell position was 0. 5 mm (sigma = 0.2 mm, max 1.3 mm). The offset resulted in dose variations to point A, bladder, and rectum of less than 1%, 2%, and 5%, respectively. Results indicate that Varian rings can show systematic and random offsets of more than 3 mm. Some can be considered defective and should be replaced. Each applicator should be individually commissioned and reproducibility should be confirmed with multiple tests. PMID- 22088999 TI - Validation of an electron Monte Carlo dose calculation algorithm in the presence of heterogeneities using EGSnrc and radiochromic film measurements. AB - The purpose of this study is to validate Eclipse's electron Monte Carlo algorithm (eMC) in heterogeneous phantoms using radiochromic films and EGSnrc as a reference Monte Carlo algorithm. Four heterogeneous phantoms are used in this study. Radiochromic films are inserted in these phantoms, including in heterogeneous media, and the measured relative dose distributions are compared to eMC calculations. Phantoms A, B, and C contain 1D heterogeneities, built with layers of lung- (phantom A) and bone- (phantoms B and C) equivalent materials sandwiched in Plastic Water. Phantom D is a thorax anthropomorphic phantom with 2D lung heterogeneities. Electron beams of 6, 9, 12 and 18 MeV from a Varian Clinac 2100 are delivered to these phantoms with a 10 * 10 cm2 applicator. Monte Carlo simulations with an independent algorithm (EGSnrc) are also used as a reference tool for two purposes: (1) as a second validation of the eMC dose calculations, and (2) to calculate the stopping power ratio between radiochromic films and bone medium, when dose is measured inside the heterogeneity. Percent depth dose (PDD) film measurements and eMC calculations agree within 2% or 3 mm for phantom A, and within 3% or 3 mm for phantoms B and C for almost all beam energies. One exception is observed with phantom B and the 6 MeV, where measured PDDs and those calculated with eMC differ by up to 4 mm. Gamma analysis of the measured and calculated 2D dose distributions in phantom D agree with criteria of 3%, 3mm for 9, 12, and 18 MeV beams, and criteria of 5%, 3 mm for the 6 MeV beam. Dose calculations in heterogeneous media with eMC agree within 3% or 3 mm with radiochromic film measurements. Six (6) MeV beams are not modeled as accurately as other beam energies. The eMC algorithm is suitable for clinical dose calculations involving lung and bone. PMID- 22089001 TI - A method to enhance spatial resolution of a 2D ion chamber array for quality control of MLC. AB - This work introduces a new method for verifying MLC leaf positions with enough spatial resolution to replace film-based methods in performing QA tests. It is implemented on a 2D ion chamber array, and it is based on the principle of varying signal response of a volumetric detector to partial irradiation. A PTW 2D ARRAY seven29 (PTW-729 2D) array was used to assess a Siemens OPTIFOCUS MLC. Partial volume response curves for chambers in the array were obtained by irradiating them with the leaves of the MLC, progressively covering varying portions of the chambers correlated with the leaf positions. The readings from the array's chambers are processed with an in-house program; it generates a reference response that translates readings into leaf positions. This principle allows discriminating errors in pairs of opposing leaves that could combine to cancel their detection with other tools. Patterns of leaf positions, similar to the Bayouth test but with different, purposefully introduced errors, were generated and used to test the effectiveness of the method. The same patterns were exposed on radiographic film and analyzed with the RIT software for validation. For four test patterns with a total of 100 errors of +/- 1 mm, +/- 2 mm and +/- 3 mm, all were correctly determined with the proposed method. The analysis of the same pattern with film using the Bayouth routine in the RIT software resulted in either somewhat low true positives combined with a large fraction of false positives, or a low true positive rate with a low false positive ratio, the results being significantly affected by the threshold selected for the analysis. This method provides an effective, easy to use tool for quantitative MLC QA assessment, with excellent spatial resolution. It can be easily applied to other 2D arrays, as long as they exhibit a partial volume detector response. PMID- 22089002 TI - Effects of voxel size and iterative reconstruction parameters on the spatial resolution of 99mTc SPECT/CT. AB - The purpose of this study was to evaluate the effects of voxel size and iterative reconstruction parameters on the radial and tangential resolution for 99mTc SPECT as a function of radial distance from isocenter. SPECT/CT scans of eight coplanar point sources of size smaller than 1 mm3 containing high concentration 99mTc solution were acquired on a SPECT/CT system with 5/8 inch NaI(Tl) detector and low-energy, high-resolution collimator. The tomographic projection images were acquired in step-and-shoot mode for 360 views over 360 degrees with 250,000 counts per view, a zoom of 2.67, and an image matrix of 256 * 256 pixels that resulted in a 0.9 * 0.9 * 0.9 mm3 SPECT voxel size over 230 mm field-of-view. The projection images were also rebinned to image matrices of 128 * 128 and 64 * 64 to yield SPECT voxel sizes of 1.8 * 1.8 * 1.8 and 3.6 * 3.6 * 3.6 mm3, respectively. The SPECT/CT datasets were reconstructed using the vendor-supplied iterative reconstruction software that incorporated collimator-specific resolution recovery, CT-based attenuation correction, and dual-energy window based scatter correction using different combinations of iterations and subsets. SPECT spatial resolution was estimated as the full width at half maximum of the radial and tangential profiles through the center of each point source in reconstructed SPECT images. Both radial and tangential resolution improved with higher iterations and subsets, and with smaller voxel sizes. Both radial and tangential resolution also improved with radial distance further away from isocenter. The magnitude of variation decreased for smaller voxel sizes and for higher number of iterations and subsets. Tangential resolution was found not to be equal to the radial resolution, and the nature of the anisotropy depended on the distribution of the radionuclide and on the reconstruction parameters used. The tangential resolution converged faster than the radial resolution, with higher iterations and subsets. SPECT resolution was isotropic and independent of radial distance when reconstructed using filtered back-projection. SPECT spatial resolution and therefore quantification of SPECT uptake via partial-volume correction in clinical images were found to depend on the nature of activity distribution within the SPECT field-of-view and on the specific choice of iterative reconstruction parameters. PMID- 22089003 TI - The impact of uncertainties associated with MammoSite brachytherapy on the dose distribution in the breast. AB - The MammoSite radiation therapy system is a novel technique for treatment of patients with early-stage breast cancer. It was developed to overcome the longer schedules associated with external-beam radiation therapy. It consists of a small balloon (4 cm in diameter) connected to an inflation channel and a catheter for the passage of a high dose rate 192Ir brachytherapy source. The device is placed into the tumor resection cavity and inflated with a mixture of saline and radiographic contrast agent to a size that fills the cavity. A high dose rate 192Ir source is driven into the balloon center using a remote afterloader to deliver the prescribed dose at a point 1 cm away from the balloon surface. There are several uncertainties that affect the dose distribution in the MammoSite brachytherapy. They include source position deviation, balloon deformation, and the concentration of the contrast medium inside the balloon. The purpose of this study is to investigate the extent of the dose perturbation for various concentrations of the contrast medium in a MammoSite balloon using Monte Carlo simulations and thermoluminescent dosimetry. This study also combines the impact of these uncertainties on the MammoSite treatment efficacy. The current study demonstrates that the combined uncertainties associated with the MammoSite brachytherapy technique--up to the value of 2 mm balloon deformation, 1 mm source deviation, and 15% contrast concentration--have no impact on the tumor control probability. PMID- 22089004 TI - Development and applicability of a quality control phantom for dental cone-beam CT. AB - Cone-beam CT (CBCT) has shown to be a useful imaging modality for various dentomaxillofacial applications. However, optimization and quality control of dental CBCT devices is hampered due to the lack of an appropriate tool for image quality assessment. To investigate the application of different image quality parameters for CBCT, a prototype polymethyl methacrylate (PMMA) cylindrical phantom with inserts for image quality analysis was developed. Applicability and reproducibility of the phantom were assessed using seven CBCT devices with different scanning protocols. Image quality parameters evaluated were: CT number correlation, contrast resolution, image homogeneity and uniformity, point spread function, and metal artifacts. Deviations of repeated measurements were between 0.0% and 3.3%. Correlation coefficients of CBCT voxel values with CT numbers ranged between 0.68 and 1.00. Contrast-to-noise ratio (CNR) values were much lower for hydroxyapatite (0 < CNR < 7.7) than for air and aluminum (5.0 < CNR < 32.8). Noise values ranged between 35 and 419. The uniformity index was between 3.3% and 11.9%. Full width at half maximum (FWHM) measurements varied between 0.43 mm and 1.07 mm. The increase of mean voxel values surrounding metal objects ranged between 6.7% and 43.0%. Results from preliminary analyses of the prototype quality control phantom showed its potential for routine quality assurance on CBCT. Large differences in image quality performance were seen between CBCT devices. Based on the initial evaluations, the phantom can be optimized and validated. PMID- 22089005 TI - Motion artifacts occurring at the lung/diaphragm interface using 4D CT attenuation correction of 4D PET scans. AB - For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D PET can reduce motion artifacts, though residual artifacts may persist depending on the CT dataset used for attenuation correction. We performed phantom studies to evaluate 4D PET images of targets near a density interface using three different methods for attenuation correction: a single 3D CT (3D CTAC), an averaged 4D CT (CINE CTAC), and a fully phase matched 4D CT (4D CTAC). A phantom was designed with two density regions corresponding to diaphragm and lung. An 8 mL sphere phantom loaded with 18F-FDG was used to represent a lung tumor and background FDG included at an 8:1 ratio. Motion patterns of sin(x) and sin4(x) were used for dynamic studies. Image data was acquired using a GE Discovery DVCT-PET/CT scanner. Attenuation correction methods were compared based on normalized recovery coefficient (NRC), as well as a novel quantity "fixed activity volume" (FAV) introduced in our report. Image metrics were compared to those determined from a 3D PET scan with no motion present (3D STATIC). Values of FAV and NRC showed significant variation over the motion cycle when corrected by 3D CTAC images. 4D CTAC- and CINE CTAC-corrected PET images reduced these motion artifacts. The amount of artifact reduction is greater when the target is surrounded by lower density material and when motion was based on sin4(x). 4D CTAC reduced artifacts more than CINE CTAC for most scenarios. For a target surrounded by water equivalent material, there was no advantage to 4D CTAC over CINE CTAC when using the sin(x) motion pattern. Attenuation correction using both 4D CTAC or CINE CTAC can reduce motion artifacts in regions that include a tissue interface such as the lung/diaphragm border. 4D CTAC is more effective than CINE CTAC at reducing artifacts in some, but not all, scenarios. PMID- 22089006 TI - Comparison of bulk electron density and voxel-based electron density treatment planning. AB - The use of magnetic resonance imaging (MRI) alone for radiation planning is limited by the lack of electron density for dose calculations. The purpose of this work is to evaluate the dosimetric accuracy of using bulk electron density as a substitute for computed tomography (CT)-derived electron density in intensity-modulated radiation therapy (IMRT) treatment planning of head and neck (HN) cancers. Ten clinically-approved, CT-based IMRT treatment plans of HN cancer were used for this study. Three dose distributions were calculated and compared for each treatment plan. The first calculation used CT-derived density and was assumed to be the most accurate. The second calculation used a homogeneous patient density of 1 g/cm3. For the third dose calculation, bone and air cavities were contoured and assigned a uniform density of 1.5 g/cm3 and 0 g/cm3, respectively. The remaining tissues were assigned a density of 1 g/cm3. The use of homogeneous anatomy resulted in up to 4%-5% deviations in dose distribution as compared to CT-derived electron density calculations. Assigning bulk density to bone and air cavities significantly improved the accuracy of the dose calculations. All parameters used to describe planning target volume coverage were within 2% of calculations based on CT-derived density. For organs at risk, most of the parameters were within 2%, with the few exceptions located in low dose regions. The data presented here show that if bone and air cavities are overridden with the proper density, it is feasible to use a bulk electron density approach for accurate dose calculation in IMRT treatment planning of HN cancers. This may overcome the problem of the lack of electron density information should MRI-only simulation be performed. PMID- 22089007 TI - Deformable registration using edge-preserving scale space for adaptive image guided radiation therapy. AB - Incorporating of daily cone-beam computer tomography (CBCT) image into online radiation therapy process can achieve adaptive image-guided radiation therapy (AIGRT). Registration of planning CT (PCT) and daily CBCT are the key issues in this process. In our work, a new multiscale deformable registration method is proposed by combining edge-preserving scale space with the multilevel free-form deformation (FFD) grids for CBCT-based AIGRT system. The edge-preserving scale space, which is able to select edges and contours of images according to their geometric size, is derived from the total variation model with the L1 norm (TV L1). At each scale, despite the noise and contrast resolution differences between the PCT and CBCT, the selected edges and contours are sufficiently strong to drive the deformation using the FFD grid, and the edge-preserving property ensures more meaningful spatial information for mutual information (MI)-based registration. At last, the deformation fields are gained by a coarse to fine manner. Furthermore, in consideration of clinical application we designed an optimal estimation of the TV-L1 parameters by minimizing the defined offset function for automated registration. Six types of patients are studied in our work, including rectum, prostate, lung, H&N (head and neck), breast, and chest cancer patients. The experiment results demonstrate the significance of the proposed method both quantitatively with ground truth known and qualitatively with ground truth unknown. The applications for AIGRT, including adaptive deformable recontouring and redosing, and DVH (dose volume histogram) analysis in the course of radiation therapy are also studied. PMID- 22089008 TI - Real-time dose reconstruction for wedged photon beams: a generalized procedure. AB - A practical and accurate generalized procedure to reconstruct the isocenter dose D(iso) for 3D conformal radiotherapy (3DCRT) has been developed for X-ray open beams supplied by linacs of different manufacturers and equipped with aSi electronic portal imaging devices (aSi EPIDs). This paper reports an extension of the method, to be applied at the wedged X-ray beams characterized by the wedge attenuation factor W(AF). Using water-equivalent solid phantoms (SPs) of different thicknesses, w, and photon square fields of sizes, L, the generalized midplane doses D(0)(W(AF), w/2,L) and generalized transit signals s(t)(0)(W(AF),w,L) by 38 beams of six different linacs were determined. The generalized data were fitted by surface equations and used together with the information of the 'record & verify' network of the centers. In this manner, for every beam, the D(iso) reconstruction was obtained in about 25 seconds after the treatment. To test the in vivo dosimetric procedure, six pelvic treatments that used conformed wedged beams were carried out with three linacs of different manufacturers. For every beam, the comparison between the reconstructed D(iso) and the D(iso,TPS) computed by the TPS, resulted in an acceptable tolerance level of +/-5%, estimated for this kind of treatment. Generally the in vivo dosimetry methods that use EPIDs require: (i) a special effort for the dosimetric commissioning with SPs of different thicknesses, and (ii) extra time for the analysis of the EPID signals. The proposed procedure simplifies the commissioning step and supplies for Varian, Elekta, and Siemens linacs equipped with the aSi EPIDs a quasi-real time in vivo dosimetry for open and wedged 3DCRT fields. PMID- 22089009 TI - Establishment of air kerma reference standard for low dose rate Cs-137 brachytherapy sources. AB - A guarded cylindrical graphite ionization chamber of nominal volume 1000 cm3 was designed and fabricated for use as a reference standard for low-dose rate 137Cs brachytherapy sources. The air kerma calibration coefficient (N(K)) of this ionization chamber was estimated analytically using Burlin's general cavity theory, as well as by the Monte Carlo simulation and validated experimentally using Amersham CDCS-J-type 137Cs reference source. In the analytical method, the N(K) was calculated for 662 keV gamma rays of 137Cs brachytherapy source. In the Monte Carlo method, the geometry of the measurement setup and physics-related input data of the 137Cs source and the surrounding material were simulated using the Monte Carlo N-Particle code. The photon energy fluence was used to arrive at the reference air kerma rate (RAKR) using mass energy absorption coefficient. The energy deposition rates were used to simulate the value of charge rate in the ionization chamber, and the N(K) was determined. The analytical and Monte Carlo values of N(K) of the cylindrical graphite ionization chamber for 137Cs brachytherapy source are in agreement within 1.07%. The deviation of analytical and Monte Carlo values from experimental values of N(K) is 0.36% and 0.72%, respectively. This agreement validates the analytical value, and establishes this chamber as a reference standard for RAKR or AKS measurement of 137Cs brachytherapy sources. PMID- 22089010 TI - Increased beam attenuation and surface dose by different couch inserts of treatment tables used in megavoltage radiotherapy. AB - The use of solid carbon fiber table materials in radiotherapy has become more common with the implementation of image-guided radiotherapy (IGRT), since the solid materials give less imaging artifacts than the so-called tennis racket couchtops. The downside of the solid carbon fiber couch inserts is that they increase the beam attenuation, resulting in increased surface doses and inaccuracies in determine the dose in the patient. The purpose of this study was to evaluate the interaction of 6 and 15 MV photons with eight different couch inserts. The presented results enable direct comparison of the attenuation properties of the studied couchtops. With a direct posterior beam the maximum attenuations reach 3.6% and 2.4% with 6 and 15 MV, respectively. The measured maximum attenuation by a couchtop with an oblique gantry angle was 10.8% and 7.4% at 6 and 15 MV energies, respectively. The skin-sparing effect was decreased substantially with every couchtop. The highest increases in surface doses were recorded to be four- and threefold, as compared to the direct posterior open field surface doses of 6 and 15 MV, respectively. In conclusion, the carbon fiber tabletops decrease the skin-sparing effect of megavoltage photon energies. The increased beam attenuation and skin doses should be taken into account in the process of treatment planning. PMID- 22089011 TI - Energy absorption buildup factors of human organs and tissues at energies and penetration depths relevant for radiotherapy and diagnostics. AB - Energy absorption geometric progression (GP) fitting parameters and the corresponding buildup factors have been computed for human organs and tissues, such as adipose tissue, blood (whole), cortical bone, brain (grey/white matter), breast tissue, eye lens, lung tissue, skeletal muscle, ovary, testis, soft tissue, and soft tissue (4-component), for the photon energy range 0.015-15 MeV and for penetration depths up to 40 mfp (mean free path). The chemical composition of human organs and tissues is seen to influence the energy absorption buildup factors. It is also found that the buildup factor of human organs and tissues changes significantly with the change of incident photon energy and effective atomic number, Z(eff). These changes are due to the dominance of different photon interaction processes in different energy regions and different chemical compositions of human organs and tissues. With the proper knowledge of buildup factors of human organs and tissues, energy absorption in the human body can be carefully controlled. The present results will help in estimating safe dose levels for radiotherapy patients and also useful in diagnostics and dosimetry. The tissue-equivalent materials for skeletal muscle, adipose tissue, cortical bone, and lung tissue are also discussed. It is observed that water and MS20 are good tissue equivalent materials for skeletal muscle in the extended energy range. PMID- 22089012 TI - Evaluating and modeling of photon beam attenuation by a standard treatment couch. AB - The purpose of this study was to evaluate beam attenuation by treatment couch and build a treatment couch model in TPS to check for beam-couch intersection at the planning stage and deal with beam attenuation by treatment couch in dose calculation. In this study, a standard treatment couch, Siemens ZXT couch, has been incorporated into Pinnacle3 8.0 TPS, based on an existing TPS tool, model based segmentation (MBS). This was done by generating the couch's model from contours of the couch, together with the density information. Both the geometric and dosimetric accuracy of the couch model were evaluated. The test of beam-couch intersection prediction showed good agreement between predicted and measured results, and the differences were within 1 degrees gantry rotation. For individual posterior oblique beams, the attenuation by metallic frames and PMMA couch top could reach nearly as high as 60% and 10%, respectively. For several posterior oblique beams (180 degrees , 220 degrees , 235 degrees ) that attenuated by the PMMA couch top, the calculated and measured dose distributions were compared. The dose differences at central axis were within 1%, and almost all points agreed with the calculations when the DD and DTA criteria of 3%/3 mm were adopted. The difference between calculated and measured attenuation factors were within 0.5%. This study demonstrates that the couch model created by MBS, which contains geometric and density information of the couch, can be used to detect the beam-couch intersection, and also is able to provide an accurate representation of the couch top attenuation properties in patient dose calculation. PMID- 22089013 TI - The dosimetric effect of mixed-energy IMRT plans for prostate cancer. AB - We investigated the effect of mixing high- and low-energy photon beams on the quality of intensity-modulated radiation therapy (IMRT) plans for patients with prostate cancer. Three different plans for each of twenty patients were generated using either 6 MV or 15 MV alone, and both 6 and 15 MV beams. All the planning parameters, goals, and constraints were set to be identical except beam energy. The dose distributions were similar in terms of target coverage, conformity, and homogeneity regardless of beam energy. The V(70Gy) of rectal wall in 6 MV, 15 MV and mixed-energy plans was 16.7%, 17.9%, and 16.3%, respectively, while V(40Gy) was 55.6%, 53.2%, and 50%. The mean dose to femoral heads in 6 MV, 15 MV, and mixed-energy plans were 31.7 Gy, 26.3 Gy, and 26.2 Gy, respectively. The integral dose of 6 MV plans was 7% larger than those of 15 MV or mixed-energy plans. These results indicated that mixed-energy IMRT plans could take advantage of the dosimetric characteristics of low- and high-energy beams. Even though the reduction of dose to the organs at risk may not be clinically relevant, mixing energy in an IMRT plan for deep-seated tumors can improve the overall plan quality. PMID- 22089014 TI - Thermoluminescent and Monte Carlo dosimetry of IR06-103Pd brachytherapy source. AB - This work presents experimental dosimetry results for a new 103Pd brachytherapy seed, in accordance with the AAPM TG-43U1 recommendation that all new low-energy interstitial brachytherapy seeds should undergo one Monte Carlo (MC) and at least one experimental dosimetry characterization. Measurements were performed using TLD-GR200A circular chip dosimeters using standard methods employing thermoluminescent dosimeters in a Perspex phantom. The Monte Carlo N-particle (MCNP) code, version 5 was used to evaluate the dose-rate distributions around this model 103Pd source in water and Perspex phantoms. The consensus value for dose-rate constant of the IR06-103Pd source was found equal to 0.690 cGy.h(-1).U( 1). The anisotropy function, F(r, theta), and the radial dose function, g(L)(r), of the seed were measured in Perspex phantom and calculated in both Perspex and liquid water phantom. The measured values were also found in good agreement with corresponding MC calculations. PMID- 22089015 TI - Comparative analysis of SmartArc-based dual arc volumetric-modulated arc radiotherapy (VMAT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma. AB - The purpose of this study was to evaluate and quantify the planning performance of SmartArc-based volumetric-modulated arc radiotherapy (VMAT) versus fixed-beam intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) using a sequential mode treatment plan. The plan quality and performance of dual arc VMAT (DA-VMAT) using the Pinnacle3 Smart-Arc system (clinical version 9.0; Philips, Fitchburg, WI, USA) were evaluated and compared with those of seven field (7F)-IMRT in 18 consecutive NPC patients. Analysis parameters included the conformity index (CI) and homogeneity index (HI) for the planning target volume (PTV), maximum and mean dose, normal tissue complication probability (NTCP) for the specified organs at risk (OARs), and comprehensive quality index (CQI) for an overall evaluation in the 11 OARs. Treatment delivery time, monitor units per fraction (MU/fr), and Gamma(3 mm, 3%) evaluations were also analyzed. DA-VMAT achieved similar target coverage and slightly better homogeneity than conventional 7F-IMRT with a similar CI and HI. NTCP values were only significantly lower in the left parotid gland (for xerostomia) for DA-VMAT plans. The mean value of CQI at 0.98 +/- 0.02 indicated a 2% benefit in sparing OARs by DA-VMAT. The MU/fr used and average delivery times appeared to show improved efficiencies in DA-VMAT. Each technique demonstrated high accuracy in dose delivery in terms of a high-quality assurance (QA) passing rate (> 98%) of the Gamma(3 mm, 3%) criterion. The major difference between DA-VMAT and 7F-IMRT using a sequential mode for treating NPC cases appears to be improved efficiency, resulting in a faster delivery time and the use of fewer MU/fr. PMID- 22089016 TI - Patient-specific CT dosimetry calculation: a feasibility study. AB - Current estimation of radiation dose from computed tomography (CT) scans on patients has relied on the measurement of Computed Tomography Dose Index (CTDI) in standard cylindrical phantoms, and calculations based on mathematical representations of "standard man". Radiation dose to both adult and pediatric patients from a CT scan has been a concern, as noted in recent reports. The purpose of this study was to investigate the feasibility of adapting a radiation treatment planning system (RTPS) to provide patient-specific CT dosimetry. A radiation treatment planning system was modified to calculate patient-specific CT dose distributions, which can be represented by dose at specific points within an organ of interest, as well as organ dose-volumes (after image segmentation) for a GE Light Speed Ultra Plus CT scanner. The RTPS calculation algorithm is based on a semi-empirical, measured correction-based algorithm, which has been well established in the radiotherapy community. Digital representations of the physical phantoms (virtual phantom) were acquired with the GE CT scanner in axial mode. Thermoluminescent dosimeter (TLDs) measurements in pediatric anthropomorphic phantoms were utilized to validate the dose at specific points within organs of interest relative to RTPS calculations and Monte Carlo simulations of the same virtual phantoms (digital representation). Congruence of the calculated and measured point doses for the same physical anthropomorphic phantom geometry was used to verify the feasibility of the method. The RTPS algorithm can be extended to calculate the organ dose by calculating a dose distribution point-by-point for a designated volume. Electron Gamma Shower (EGSnrc) codes for radiation transport calculations developed by National Research Council of Canada (NRCC) were utilized to perform the Monte Carlo (MC) simulation. In general, the RTPS and MC dose calculations are within 10% of the TLD measurements for the infant and child chest scans. With respect to the dose comparisons for the head, the RTPS dose calculations are slightly higher (10% 20%) than the TLD measurements, while the MC results were within 10% of the TLD measurements. The advantage of the algebraic dose calculation engine of the RTPS is a substantially reduced computation time (minutes vs. days) relative to Monte Carlo calculations, as well as providing patient-specific dose estimation. It also provides the basis for a more elaborate reporting of dosimetric results, such as patient specific organ dose volumes after image segmentation. PMID- 22089018 TI - Measurements to predict the time of target replacement of a helical tomotherapy. AB - Intensity-modulated radiation therapy (IMRT) requires more beam-on time than normal open field treatment. Consequently, the machines wear out and need more spare parts. A helical tomotherapy treatment unit needs a periodical tungsten target replacement, which is a time consuming event. To be able to predict the next replacement would be quite valuable. We observed unexpected variations towards the end of the target lifetime in the performed pretreatment measurements for patient plan verification. Thus, we retrospectively analyze the measurements of our quality assurance program. The time dependence of the quotient of two simultaneous dose measurements at different depths within a phantom for a fixed open field irradiation is evaluated. We also assess the time-dependent changes of an IMRT plan measurement and of a relative depth dose curve measurement. Additionally, we performed a Monte Carlo simulation with Geant4 to understand the physical reasons for the measured values. Our measurements show that the dose at a specified depth compared to the dose in shallower regions of the phantom declines towards the end of the target lifetime. This reproducible effect can be due to the lowering of the mean energy of the X-ray spectrum. These results are supported by the measurements of the IMRT plan, as well as the study of the relative depth dose curve. Furthermore, the simulation is consistent with these findings since it provides a possible explanation for the reduction of the mean energy for thinner targets. It could be due to the lowering of low energy photon self-absorption in a worn out and therefore thinner target. We state a threshold value for our measurement at which a target replacement should be initiated. Measurements to observe a change in the energy are good predictors of the need for a target replacement. However, since all results support the softening of the spectrum hypothesis, all depth-dependent setups are viable for analyzing the deterioration of the tungsten target. The suggested measurements and criteria to replace the target can be very helpful for every user of a TomoTherapy machine. PMID- 22089017 TI - Expanding the use of real-time electromagnetic tracking in radiation oncology. AB - In the past 10 years, techniques to improve radiotherapy delivery, such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT) for both inter- and intrafraction tumor localization, and hypofractionated delivery techniques such as stereotactic body radiation therapy (SBRT), have evolved tremendously. This review article focuses on only one part of that evolution, electromagnetic tracking in radiation therapy. Electromagnetic tracking is still a growing technology in radiation oncology and, as such, the clinical applications are limited, the expense is high, and the reimbursement is insufficient to cover these costs. At the same time, current experience with electromagnetic tracking applied to various clinical tumor sites indicates that the potential benefits of electromagnetic tracking could be significant for patients receiving radiation therapy. Daily use of these tracking systems is minimally invasive and delivers no additional ionizing radiation to the patient, and these systems can provide explicit tumor motion data. Although there are a number of technical and fiscal issues that need to be addressed, electromagnetic tracking systems are expected to play a continued role in improving the precision of radiation delivery. PMID- 22089019 TI - The effect of gantry spacing resolution on plan quality in a single modulated arc optimization. AB - Volumetric-modulated arc technique (VMAT) is an efficient form of IMRT delivery. It is advantageous over conventional IMRT in terms of treatment delivery time. This study investigates the relation between the number of segments and plan quality in VMAT optimization for a single modulated arc. Five prostate, five lung, and five head-and-neck (HN) patient plans were studied retrospectively. For each case, four VMAT plans were generated. The plans differed only in the number of control points used in the optimization process. The control points were spaced 2 degrees , 3 degrees , 4 degrees , and 6 degrees apart, respectively. All of the optimization parameters were the same among the four schemes. The 2 degrees spacing plan was used as a reference to which the other three plans were compared. The plan quality was assessed by comparison of dose indices (DIs) and generalized equivalent uniform doses (gEUDs) for targets and critical structures. All optimization schemes generated clinically acceptable plans. The differences between the majority of reference and compared DIs and gEUDs were within 3%. DIs and gEUDs which differed in excess of 3% corresponded to dose levels well below the organ tolerances. The DI and the gEUD differences increased with an increase in plan complexity from prostates to HNs. Optimization with gantry spacing resolution of 4 degrees seems to be a very balanced alternative between plan quality and plan complexity. PMID- 22089020 TI - Dependence of intrafraction motion on fraction duration for pediatric patients with brain tumors. AB - The purpose of this study was to quantify the intrafraction motion of pediatric patients with brain tumors during radiation therapy and investigate any correlation between motion, use of general anesthesia, and daily treatment duration. 100 pediatric patients with a mean age of 8.5 years (range: 1.0 to 17.8) were included in this prospective study. Forty-one patients required general anesthesia during treatment, mean age 4.8 years; 59 patients did not, mean age 11.2 years. Each patient had an intracranial tumor and was treated in the supine position with a thermoplastic facemask and headrest for immobilization. A pretreatment localization CBCT was acquired for each treatment fraction and a post-treatment CBCT was acquired every other fraction. If the magnitude of the patient's position pre-CBCT offset was >= 2 mm, the position was corrected. The difference between the patient's position based on the post-CBCT and the assumed position at the start of treatment (either the pre-CBCT offset if the magnitude was < 2 mm, or 0 offset due to correction) was determined and labeled intrafraction motion. Correlations between daily treatment duration and intrafraction motion were examined. There was an average of 14.2 post-CBCTs acquired per patient. The magnitude of the mean intrafraction motion was 1.2 +/- 0.8 mm for patients requiring general anesthesia, and 1.5 +/- 1.2 mm for those without (p < 0.001). The mean offset in each direction was less than 0.5 mm for both cohorts. There was no correlation between daily treatment duration and the magnitude of intrafraction motion. The intrafraction motion of pediatric patients undergoing external beam therapy for intracranial tumors is small, < 2 mm, and is independent of the daily treatment duration. PMID- 22089021 TI - Antiscatter grid use in pediatric digital tomosynthesis imaging. AB - The objective of this study was to assess the effect of antiscatter grid use on tomosynthesis image quality. We performed an observer study that rated the image quality of digital tomosynthesis scout radiographs and slice images of a Leeds TO.20 contrast-detail test object embedded in acrylic with and without a grid. We considered 10, 15, 20 and 25 cm of acrylic to represent the wide range of patient thicknesses encountered in pediatric imaging. We also acquired and rated images without a grid at an increased patient dose. The readers counted the total number of visible details in each image as a measure of relative image quality. We observed that the antiscatter grid improves tomosynthesis image quality compared to the grid-out case, which received image quality scores similar to grid-in radiography. Our results suggest that, in order to achieve the best image quality in exchange for the increase in patient dose, it may often be appropriate to include an antiscatter grid for pediatric tomosynthesis imaging, particularly if the patient thickness is greater than 10 cm. PMID- 22089022 TI - Isocenter verification for linac-based stereotactic radiation therapy: review of principles and techniques. AB - There have been several manual, semi-automatic and fully-automatic methods proposed for verification of the position of mechanical isocenter as part of comprehensive quality assurance programs required for linear accelerator-based stereotactic radiosurgery/radiotherapy (SRS/SRT) treatments. In this paper, a systematic review has been carried out to discuss the present methods for isocenter verification and compare their characteristics, to help physicists in making a decision on selection of their quality assurance routine. PMID- 22089023 TI - Calculating the peak skin dose resulting from fluoroscopically guided interventions. Part I: Methods. AB - While direct measurement of the peak skin dose resulting from a fluoroscopically guided procedure is possible, the decision must be made a priori at additional cost and time. It is most often the case that the need for accurate knowledge of the peak skin dose is realized only after a procedure has been completed, or after a suspected reaction has been discovered. Part I of this review article discusses methods for calculating the peak skin dose across a range of clinical scenarios. In some cases, a wealth of data are available, while in other cases few data are available and additional data must be measured in order to estimate the peak skin dose. Data may be gathered from a dose report, the DICOM headers of images, or from staff and physician interviews. After data are gathered, specific steps must be followed to convert dose metrics, such as the reference point air kerma (K(a,r)) or the kerma area product (KAP), into peak skin dose. These steps require knowledge of other related factors, such as the f-factor and the backscatter factor, tables of which are provided in this manuscript. Sources of error and the impact of these errors on the accuracy of the final estimate of the peak skin dose are discussed. PMID- 22089025 TI - Pore-expanded SBA-15 sulfonic acid silicas for biodiesel synthesis. AB - Here we present the first application of pore-expanded SBA-15 in heterogeneous catalysis. Pore expansion over the range 6-14 nm confers a striking activity enhancement towards fatty acid methyl ester (FAME) synthesis from triglycerides (TAG), and free fatty acid (FFA), attributed to improved mass transport and acid site accessibility. PMID- 22089026 TI - Flexible microfluidic cloth-based analytical devices using a low-cost wax patterning technique. AB - This paper describes the fabrication of microfluidic cloth-based analytical devices (MUCADs) using a simple wax patterning method on cotton cloth for performing colorimetric bioassays. Commercial cotton cloth fabric is proposed as a new inexpensive, lightweight, and flexible platform for fabricating two- (2D) and three-dimensional (3D) microfluidic systems. We demonstrated that the wicking property of the cotton microfluidic channel can be improved by scouring in soda ash (Na(2)CO(3)) solution which will remove the natural surface wax and expose the underlying texture of the cellulose fiber. After this treatment, we fabricated narrow hydrophilic channels with hydrophobic barriers made from patterned wax to define the 2D microfluidic devices. The designed pattern is carved on wax-impregnated paper, and subsequently transferred to attached cotton cloth by heat treatment. To further obtain 3D microfluidic devices having multiple layers of pattern, a single layer of wax patterned cloth can be folded along a predefined folding line and subsequently pressed using mechanical force. All the fabrication steps are simple and low cost since no special equipment is required. Diagnostic application of cloth-based devices is shown by the development of simple devices that wick and distribute microvolumes of simulated body fluids along the hydrophilic channels into reaction zones to react with analytical reagents. Colorimetric detection of bovine serum albumin (BSA) in artificial urine is carried out by direct visual observation of bromophenol blue (BPB) colour change in the reaction zones. Finally, we show the flexibility of the novel microfluidic platform by conducting a similar reaction in a bent pinned MUCAD. PMID- 22089027 TI - Neonatal Fc receptor for IgG (FcRn) expressed in the gastric epithelium regulates bacterial infection in mice. AB - Neonatal Fc receptors for immunoglobulin (Ig)G (FcRn) assume a central role in regulating host IgG levels and IgG transport across polarized epithelial barriers. We have attempted to elucidate the contribution of FcRn in controlling Helicobacter infection in the stomach. C57BL/6J wild-type or FcRn(-/-) mice were infected with Helicobacter heilmannii, and gastric lesions, bacterial load and the levels of antigen-specific IgG in serum and gastric juice were analyzed. The elevated levels of anti-H. heimannii IgG in gastric juice were observed exclusively in wild-type mice but not in FcRn(-/-) mice. In contrast, an increase in lymphoid follicles and bacterial loads along with deeper gastric epithelium invasion were noted in FcRn(-/-) mice. C57BL/6J wild-type or FcRn(-/-) mice were also infected with Helicobacter pylori SS1, and the results of the bacterial load in stomachs of these mice and the anti-H. pylori IgG levels in serum and gastric juice were similar to those from H. heilmannii infection. Our data suggest that FcRn can be functionally expressed in the stomach, which is involved in transcytosis of IgG, and prevent colonization by H. heilmannii and the associated pathological consequences of infection. PMID- 22089031 TI - Synthesis, structures, and properties of ruthenium(II) complexes of N-(1,10 phenanthrolin-2-yl)imidazolylidenes. AB - Mononuclear ruthenium complexes [RuCl(L1)(CH(3)CN)(2)](PF(6)) (2a), [RuCl(L2)(CH(3)CN)(2)](PF(6)) (2b), [Ru(L1)(CH(3)CN)(3)](PF(6))(2) (4a), [Ru(L2)(CH(3)CN)(3)](PF(6))(2) (4b), [Ru(L2)(2)](PF(6))(2) (5), [RuCl(L1)(CH(3)CN)(PPh(3))](PF(6)) (6), [RuCl(L1)(CO)(2)](PF(6)) (7), and [RuCl(L1)(CO)(PPh(3))](PF(6)) (8), and a tetranuclear complex [Ru(2)Ag(2)Cl(2)(L1)(2)(CH(3)CN)(6)](PF(6))(4) (3) containing 3-(1,10 phenanthrolin-2-yl)-1-(pyridin-2-ylmethyl)imidazolylidene (L1) and 3-butyl-1 (1,10-phenanthrolin-2-yl)imidazolylidene (L2) have been prepared and fully characterized by NMR, ESI-MS, UV-vis spectroscopy, and X-ray crystallography. Both L1 and L2 act as pincer NNC donors coordinated to ruthenium (II) ion. In 3, the Ru(II) and Ag(I) ions are linked by two bridging Cl(-) through a rhomboid Ag(2)Cl(2) ring with two Ru(II) extending to above and down the plane. Complexes 2-8 show absorption maximum over the 354-428 nm blueshifted compared to Ru(bpy)(3)(2+) due to strong sigma-donating and weak pi-acceptor properties of NHC ligands. Electrochemical studies show Ru(II)/Ru(III) couples over 0.578-1.274 V. PMID- 22089029 TI - Foreskin T-cell subsets differ substantially from blood with respect to HIV co receptor expression, inflammatory profile, and memory status. AB - The foreskin is the main site of heterosexual human immunodeficiency virus (HIV) acquisition in uncircumcised men, but functional data regarding T-cell subsets present at this site are lacking. Foreskin tissue and blood were obtained from Ugandan men undergoing elective adult circumcision. Tissue was treated by mechanical and enzymatic digestion followed by T-cell subset identification and assessment of cytokine production using flow cytometry. Foreskin CD4(+) T cells were predominantly an effector memory phenotype, and compared with blood they displayed a higher frequency of CCR5 expression (42.0% vs. 9.9%) and interleukin 17 production. There was no difference in T-regulatory cell frequency, but interferon-gamma and tumor necrosis factor-alpha production were increased in foreskin CD8(+) T cells. These novel techniques demonstrate that the foreskin represents a proinflammatory milieu that is enriched for HIV-susceptible T-cell subsets. Further characterization of foreskin T-cell subsets may help to define the correlates of HIV susceptibility in the foreskin. PMID- 22089028 TI - Pulmonary-intestinal cross-talk in mucosal inflammatory disease. AB - Chronic obstructive pulmonary disease (COPD) and inflammatory bowel diseases (IBDs) are chronic inflammatory diseases of mucosal tissues that affect the respiratory and gastrointestinal tracts, respectively. They share many similarities in epidemiological and clinical characteristics, as well as in inflammatory pathologies. Importantly, both conditions are accompanied by systemic comorbidities that are largely overlooked in both basic and clinical research. Therefore, consideration of these complications may maximize the efficacy of prevention and treatment approaches. Here, we examine both the intestinal involvement in COPD and the pulmonary manifestations of IBD. We also review the evidence for inflammatory organ cross-talk that may drive these associations, and discuss the current frontiers of research into these issues. PMID- 22089030 TI - Opposing consequences of IL-23 signaling mediated by innate and adaptive cells in chemically induced colitis in mice. AB - The interleukin-23 (IL-23) pathway has emerged as a promising therapeutic target for inflammatory bowel disease. Although the pathogenic role of IL-23 receptor (IL-23R) on T lymphocytes is well established, its function on innate immune cells has not been thoroughly examined. Here we investigate the consequence of IL 23R deletion in dextran sulfate sodium (DSS)-induced colitis. In IL23R(-/-) and IL23p19(-/-) mice, we observed decreased weight loss and reduced leukocyte infiltrate following DSS exposure. Surprisingly, when the IL-23R(-/-) allele was crossed into Rag2(-/-) mice, we observed exacerbated disease, increased epithelial damage, reduced pSTAT3 in the epithelium, and delayed recovery of IL23R(-/-)Rag2(-/-) mice. This phenotype was rescued with exogenous IL22-Fc, and epithelial pSTAT3 was restored. Depletion of Thy1(+) innate lymphoid cells eliminated the majority of IL-22 production in the colon lamina propria of DSS treated Rag2(-/-) mice, suggesting that these are the major IL-23 responsive innate cells in this context. In summary, we provide evidence for opposing consequences of IL-23R on innate and adaptive lymphoid cells in murine colitis. PMID- 22089032 TI - Dynamics of screw and plate interaction. PMID- 22089033 TI - Comment on "HCl adsorption on ice at low temperature: a combined X-ray absorption, photoemission and infrared study" by P. Parent, J. Lasne, G. Marcotte and C. Laffon, Phys. Chem. Chem. Phys., 2011, 13, 7142. AB - On the basis of NEXAFS, photoemission and FTIR spectra of ice films with low doses of adsorbed HCl, the authors of the PCCP paper "HCl adsorption on ice at low temperature: a combined X-ray absorption, photoemission and infrared study", Phys. Chem. Chem. Phys., 2011, 13, 7142, have come to conclusions regarding the behavior of submonolayer amounts of HCl at 50 K that contradict published results of the authors of this Comment. Our purpose is to argue that the conclusion, attributed going forward to PLML (authors' initials), that nearly 100% of HCl ionizes for dosage levels near to 0.16 monolayer (ML) or 0.3 Langmuir (L) at 50 K is questionable. Rather, we reaffirm our conclusions of much lower levels of ionization for similar temperatures and HCl dosages based on reactive ion scattering (RIS) and low energy sputtering (LES) data for ice films and FTIR spectra of ice nanocrystals. A second current paper by Ayotte et al., J. Phys. Chem. A, 2011, 115, 6002, that largely parallels in method and results the RAIR spectroscopy of PLML, is also given special notice. PMID- 22089034 TI - Changes in reproductive life-history strategies in response to nest density in a shell-brooding cichlid, Telmatochromis vittatus. AB - To determine whether the appearance of a reproductively parasitic tactic varies, and how this variation affects territorial males of the Lake Tanganyika cichlid fish Telmatochromis vittatus, we examined the reproductive ecology of territorial males in Mtondwe and compared it with that of a neighboring Wonzye population, where nest density differs from that at Mtondwe. In Wonzye, with high nest density, male tactics change with their body size from a territorial to a non territorial parasitic tactic called piracy in which they conquer several nests defended by territorial males and take over the nests while females are spawning. These "pirate" males could decrease the costs incurred by travelling among nests by exclusively targeting aggregations of nests in close proximity while avoiding separate nests. Territorial males in Wonzye sacrifice the potential higher attractiveness offered by large nests and instead compete for nests farther from neighbors on which pirates less frequently intrude. In contrast, the Mtondwe population had lower nest density and piracy was absent. Given that the success of piracy depends on the close proximity of nests, nest density is likely responsible for the observed variation in the occurrence of piracy between the two populations. Furthermore, in Mtondwe, territorial males competed for larger nests and were smaller than the territorial males in Wonzye. Thus, this lower nest density may free territorial males from the selection pressures for increased size caused by both defense against nest piracy and the need to develop into pirates as they grow. PMID- 22089035 TI - Inactivation of estrogen receptor by Schistosoma haematobium total antigen in bladder urothelial cells. AB - We recently reported the expression of an estradiol-like molecule by a trematode parasite Schistosoma haematobium. We further established that this estradiol-like molecule is an antagonist of estradiol, repressing the transcriptional activity of the estrogen receptor (ER) in estrogen-responsive MCF7 cells and also that S. haematobium total antigen (Sh) contains estrogenic molecules detected by mass spectrometry. In the present study, we used HCV29 cells, a cell line derived from normal urothelial cells, as well as an in vivo model to evaluate the expression of ER in the bladders of Sh-instilled animals. We show that, similarly to MCF7 cells, Sh down-regulates the transcriptional activity of ER in HCV29 cells and also in the bladders of Sh-treated mice. The antiestrogenic activity of the S. haematobium extract and its repressive role in ER could have implications in the carcinogenic process in bladders with S. haematobium infection. PMID- 22089037 TI - Sledging is still a seasonal source of serious injury in Scottish children. AB - In 2002 it was highlighted that sledging results in serious injuries in the paediatric population and safety recommendations were made. The aim of this study was to re-examine the number, severity and aetiology of sledging-related trauma. This was a retrospective study performed in the Paediatric Emergency Department (PED) of the Royal Aberdeen Children's Hospital (RACH) during two periods totalling 12 days, when there was continuous snow ground cover. Records of all attendances were scrutinized to identify patients with sledging injuries. The nature, mechanism and severity of injury, and subsequent management were then analysed. Of 403 PED attendances, 45 (11%) were sledging related with 16 (36%) fractures and 13 (29%) head injuries. Eight patients (18%) were admitted to hospital and three (7%) required an operation. Collision with a stationary object was the most common reason for injury (51%), followed by the adoption of a dangerous sledging position or use of a stationary jump. No patients were wearing a helmet. In conclusion, there has been little change in the epidemiology and aetiology of paediatric sledging injuries since 2002. Work is needed to inform parents of the previously recommended safety measures that could reduce the morbidity of this activity without detracting from the enjoyment. PMID- 22089036 TI - All I want for coagulation. AB - Evidence-based medicine underpins modern practice of medicine. This paper describes a fictional consultation between Santa Claus and a doctor regarding deep vein thrombosis (DVT) prophylaxis, giving a review of the evidence for DVT prophylaxis in travellers while exposing the difficulty in applying evidence to atypical clinical encounters. Medline and the Cochrane Library were searched, and guidelines reviewed. Keywords used were DVT, thromboembolism, deep vein thrombosis and air travel-related venous thromboembolism. All relevant studies found, have been included in this review, with additional studies identified from the references in these articles. In conclusion, compression stockings, with or without a one-off dose of either aspirin or heparin, are the most evidence-based approaches for prophylaxis in someone with established risk factors for DVT prior to a long-haul flight. Simple exercises should also be encouraged. PMID- 22089038 TI - A study of thromboprophylactic practices of Scottish orthopaedic surgeons in patients undergoing total hip replacements. Should practice change with new guidelines? AB - Despite increasing scientific investigation, the best method for preventing postoperative thromboembolism in patients undergoing a total hip replacement (THR) remains unclear. National Institute for Health and Clinical Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the prevention of thromboembolism have caused much controversy. We surveyed Scottish surgeons regarding their thromboprophylaxis prescribing after THR. Questionnaires were sent to all Scottish orthopaedic consultants. They were asked about routine pharmacological and mechanical prophylaxis in patients undergoing a THR. Comparison was made with a previous survey done in 2003. The response rate was 75%. The survey showed an increased use of pharmacological prophylaxis from 93% to 100%. This was due to the increased use of aspirin from 51% to 64%. The use of low molecular weight heparin has remained constant at 51%. No surgeons routinely use warfarin, un-fractionated heparin or fondaparinux. Use of graded compression stockings has increased from 59% to 70%. In conclusion, there is increasing evidence that patients undergoing THR should receive extended prophylaxis for up to 35 days. Oral agents such as dabigatran and rivaroxaban have offered a new option for oral extended prescribing. The results in change of practice must be closely audited. PMID- 22089039 TI - A new approach to scoring systems to improve identification of acute medical admissions that will require critical care. AB - Removal of the intensive care unit (ICU) at the Vale of Leven Hospital mandated the identification and transfer out of those acute medical admissions with a high risk of requiring ICU. The aim of the study was to develop triaging tools that identified such patients and compare them with other scoring systems. The methodology included a retrospective analysis of physiological and arterial gas measurements from 1976 acute medical admissions produced PREEMPT-1 (PRE-critical Emergency Medical Patient Triage). A simpler one for ambulance use (PREAMBLE-1 [PRE-Admission Medical Blue-Light Emergency]) was produced by the addition of peripheral oxygen saturation to a modification of MEWS (Modified Early Warning Score). Prospective application of these tools produced a larger database of 4447 acute admissions from which logistic regression models produced PREEMPT-2 and PREAMBLE-2, which were then compared with the original systems and seven other early warning scoring systems. Results showed that in patients with arterial gases, the area under the receiver operator characteristic curve was significantly higher in PREEMPT-2 (89.1%) and PREAMBLE-2 (84.4%) than all other scoring systems. Similarly, in all patients, it was higher in PREAMBLE-2 (92.4%) than PREAMBLE-1 (88.1%) and the other scoring systems. In conclusion, risk of requiring ICU can be more accurately predicted using PREEMPT-2 and PREAMBLE-2, as described here, than by other early warning scoring systems developed over recent years. PMID- 22089040 TI - Impact of national guidelines on family history breast cancer surveillance. AB - The breast cancer risk of women already under family history surveillance was accurately assessed according to national guidelines in an attempt to rationalize the service. Women attending two breast units in Glasgow between November 2003 and February 2005 were included. One thousand and five women under annual surveillance were assessed and had their relatives diagnoses verified. Four hundred and ninety-seven women were at significantly increased risk and eligible for follow-up. Five hundred and eight (50%) women attending were not eligible for family history surveillance, and 498 (98%) of these women accepted discharge. In conclusion, national guidelines have helped to more clearly define women who should undergo surveillance. This avoids unnecessary and potentially harmful routine investigations, and the service has been improved. PMID- 22089041 TI - Outcomes following a dedicated period of research during surgical training. AB - With recent 'working-time'-related changes to surgical training structure, the value of dedicated research during surgical training has been questioned. Online survey examining career and academic outcomes following a period of surgically related dedicated research at a Scottish University between 1972 and 2007. Of 58 individuals identified, contact details were available for 49 and 43 (88%) responded. Ninety-five percent (n = 41) of respondents continue to pursue a career in surgery and 41% (n = 17) are currently in academic positions. Ninety one percent (n = 39) had published one or more first-author peer-reviewed articles directly related to their research, with 53% (n = 23) publishing three or more. Respondents with a clinical component to their research published significantly more papers than those with purely laboratory-based research (P = 0.04). Eighty-one percent (n = 35) thought that research was necessary for career progression, but only 42% (n = 18) felt research should be integral to training. In conclusion, the majority of surgical trainees completing a dedicated research period, published papers and continued to pursue a surgical career with a research interest. A period of dedicated research was thought necessary for career progression, but few thought dedicated research should be integral to surgical training. PMID- 22089042 TI - Effect of intradermal anaesthesia on success rate and pain of intravenous cannulation: a randomized non-blind crossover study. AB - Intravenous cannulation is a commonly performed procedure. This study aimed to determine whether the success rate and pain of intravenous cannulation is affected by prior injection of intradermal lidocaine. Intravenous cannulation was performed twice in 45 healthy volunteers. Intradermal lidocaine was administered prior to one of these cannulations. The outcome measures were success or failure of cannulation, and pain of cannulation, measured with a 100 mm visual analogue pain scale. The success rate of intravenous cannulation with and without prior intradermal lidocaine was 54% and 76%, respectively. The difference was 22.0% (95% CI 1.5-27.8%; P = 0.03). Log-linear analysis for three-way interaction between the variables (outcome, vascular condition and use of lidocaine) showed a significant influence of vascular condition on outcome (G(2) 24.6, P < 0.001). The mean (SD) pain scores in the control and intervention group were 34.8 (21.0) and 13.6 (13.2) mm, respectively. The difference between the mean pain scores was 21.2 mm (95% CI 15.1-27.3 mm). In conclusion, the success rate of intravenous cannulation may be reduced with the use of intradermal lidocaine, but success rate is primarily dependent on vascular condition. Intradermal lidocaine achieves a clinically significant reduction in the pain of intravenous cannulation. PMID- 22089043 TI - A preliminary clinical study on high-intensity focused ultrasound therapy for tubal pregnancy. AB - Our aim was to explore the clinical application value of high-intensity focused ultrasound (HIFU) therapy for tubal pregnancy. Forty hospitalized patients with tubal pregnancies (28 cases of non-ruptured tubal pregnancy and 12 cases of ruptured tubal pregnancy) were selected to receive HIFU therapy. Serum human chorionic gonadotropin (beta-HCG) concentrations were compared before and after treatment. Serum beta-HCG was measured weekly and patients received observation only if the concentration decreased by 15% or more, compared with the previous value. Patients were given supplement HIFU therapy if the decrease in the serum beta-HCG was <15% within two weeks. Ultrasound was used to detect the volume changes in the ectopic lesions before and after treatment, and changes in vital signs and complications were recorded. Contrast-enhanced ultrasonography was used to assess fallopian tube patency after treatment. HIFU treatment was successful in 33 of the 40 patients (82%). Seven patients failed HIFU treatment and received surgical therapy (18%). Before and after treatment, serum beta-HCG concentrations and lesion volume were significantly different (P < 0.05, P < 0.01, respectively). Post-treatment tubal contrast-enhanced ultrasonography showed tubal patency on the affected side in 21 cases (64%) at six months and in 27 cases (82%) at 12 months. In conclusion, HIFU is safe and effective, and can be a treatment option for tubal pregnancy. PMID- 22089044 TI - Effect of socioeconomic deprivation and the appointment of Welfare Attorneys. AB - Most patients in intensive care unit (ICU) lack decision-making ability. The Adults with Incapacity (Scotland) Act 2000 allows someone to appoint a Welfare Attorney (WA) to act on their behalf should they lose capacity. Scotland has areas of major socioeconomic deprivation associated with lower life-expectancy and with a lack of knowledge about and consequently difficulty accessing services. The effect of socioeconomic deprivation on WA registration was investigated. A complete list of registered WAs was categorized by deprivation. The Public Guardian, Scotland indicated whether patients admitted to ICU at Glasgow Royal (April 2006-May 2009) had a WA registered. All Scottish ICU admissions (2004-2008) were categorized by deprivation. Twelve of 1152 ICU patients at Glasgow Royal had a WA. Of 165,997 WAs registered, 5984 were in the most deprived and 27,970 in the most affluent areas. Overall, 3.9% of the Scottish population had a WA (1.4% in the most, 6.5% in the least deprived population decile). In conclusion, the uptake of WAs was low, especially in deprived areas. The reasons could include a lack of knowledge, not anticipating the need for a WA or not being confident in the process. Any educational package needs to target the most socioeconomically disadvantaged. PMID- 22089045 TI - The Scottish Liver Transplant Unit: current and future perspectives. AB - The Scottish Liver Transplant Unit (SLTU) opened in 1992 and has now performed over 900 liver transplants. During this time there have been major changes in both organ donation and transplantation. Currently liver transplantation is restricted by limited organ supply. Scotland has one of the lowest rates of organ donation in Europe and one of the most rapidly increasing rates of cirrhosis. The consequent waiting list mortality has driven innovations including increasing use of marginal grafts, organs donated after cardiac death, split-liver transplants and the development of living-donor liver transplantation. To maintain liver transplantation, there is an urgent need to increase organ donation rates and to find novel treatments which optimize outcomes from marginal grafts. This review addresses the surgical aspects of liver transplantation and how these have evolved over the two past decades. Major changes are currently underway in organ donation organization, and there is continuing refinement of organ treatment and storage. A number of measures to maintain and improve organ preservation and function are currently being evaluated in clinical trials, and cell therapy holds significant potential for the future. Scotland has a rising need for liver transplantation and the SLTU continues to provide high-quality care and to be at the forefront of the latest advances in organ transplantation. PMID- 22089046 TI - The case of King Richard III. AB - In this short essay we will discuss the possible diseases of King Richard III according to the descriptions in Shakespeare's plays King Richard III and Henry VI. Furthermore, it is shown that the description of the defeated enemy as physically and mentally deformed is part of a long tradition which has its roots in Ancient Greece. PMID- 22089048 TI - Popliteal cystic adventitial disease: a case report and literature review. AB - Cystic adventitial disease (CAD) is rare. The popliteal artery is the most commonly affected artery. Patients with CAD are usually young and present with ischaemic lower limb symptoms. We report a case of a 39-year-old male patient with popliteal CAD. The affected segment was resected and repaired with an interposition vein graft. In conclusion, we highlight the importance of correct diagnosis and outline the different management strategies. PMID- 22089049 TI - A case of arm swelling and muscle Wii-kness. AB - The Nintendo Wii is now the world's most popular home games console owing to its simple interface and replication of sports activities. Although safety advice is provided by the manufacturer, a number of injuries have previously been described. We describe a case of arm swelling with associated rise in serum creatine kinase to over 8000 U/L in a man, following unaccustomed and sustained strenuous muscle exertion through the use of the Nintendo Wii. His condition spontaneously resolved with rest and conservative measures. His presentation represents significant muscle injury through the use of this games console and the replication of sporting activities; physicians should be aware of the variety of musculoskeletal presentations such use of these devices can produce. PMID- 22089050 TI - Gastric Schwannoma or GIST: accuracy of preoperative diagnosis? AB - Mesenchymal cell tumours of the gastrointestinal tract are rare in western society. Gastrointestinal stromal tumour (GIST) is the most common of this group of tumours. Gastric schwannoma is rarer, accounting for only 0.2% of all gastric tumours and 4% of all benign gastric neoplasms. Indeed, schwannoma has only been recognized as a primary gastrointestinal tumour in the last 20 years through advances in pathological techniques. We report a rare case of gastric schwannoma, the endoscopic and radiological features of which were indistinguishable from a GIST. Due to the diagnostic uncertainty, surgical resection is the treatment of choice. Development of more reliable diagnostic methods, such as endoscopic core biopsy, may help the accuracy of preoperative diagnosis. PMID- 22089051 TI - Tuberculous pericarditis: a diagnostic quandary. AB - Tuberculous pericarditis is uncommon in the Western world, and can prove a diagnostic quandary in that confirmation of the diagnosis and culture of mycobacteria can be difficult. We present a case of tuberculous pericarditis where endobronchial ultrasound-guided transbronchial needle biopsy of a pathological lymph node provided the diagnosis after other methods of investigation had proved futile. PMID- 22089052 TI - Nocardiosis complicated with Addison's disease. AB - A 77-year-old woman presented with subacute respiratory symptoms which were demonstrated to be due to nocardiosis. After initial improvement with antimicrobial therapy, new symptoms appeared, consisting of persistent vomits, abdominal pain and hypotension, which led to the diagnosis of Addison's disease. PMID- 22089053 TI - Synchronous presentation of Gaucher disease and solitary plasmacytoma with progression to multiple myeloma. AB - A 37-year-old Polish immigrant presented with unilateral hip pain and difficulty weight-bearing. Plain radiography and magnetic resonance imaging (MRI) revealed a lytic lesion in the acetabulum, with abnormal serum electrophoresis and bone marrow biopsy. The patient was diagnosed with two rare conditions presenting synchronously - Gaucher disease and plasmacytoma. He was treated with enzyme therapy and radiotherapy, but subsequently developed a recurrence of plasmacytoma in the right femur, confirmed with bone marrow biopsy. This was also treated with radiotherapy, followed by a retrograde femoral nail to reduce the risk of pathological fracture. The patient went on to develop multiple lytic lesions in the ribs and vertebra, seen on MRI. Further bone marrow biopsy confirmed dissemination of the plasmacytoma into multiple myeloma, for which he was treated with systemic chemotherapy. In patients presenting with refractory bone or joint pain, haematological and histological investigations should be considered to exclude less common diagnoses. PMID- 22089054 TI - Toxic levels of glycosides in herbal medication: a potential cause of hyperkalaemia. AB - We report a previously healthy man presenting with life-threatening hyperkalaemia and heart failure. The only possible cause was thought to be the long list of herbal medications he was taking, several of which contained significant amounts of cardiac glycosides. Hyperkalaemia is known to be associated with digoxin toxicity and we present this as the likely cause in this case, and emphasize the importance of a thorough drug history in forming a differential diagnosis. PMID- 22089055 TI - Imaging in chronic cough in paediatrics. AB - Chronic cough is a common presentation in paediatrics. We describe a case which highlights the need for careful history taking and summarize the key clinical features which should prompt a clinician to perform a chest X-ray. PMID- 22089056 TI - Chemolysis of calcium oxalate stones: study in vitro and possible clinical application. AB - The flow cell modeling clinical conditions have been used to study the interaction between dilute chemolytic solutions and large calcium oxalate renal stones. The stone treatment with 5% disodium ethylenediaminetetraacetate aqueous solutions or citrate buffer are found not to provide notable disruption of the samples studied. The significant improvement is reached with the mixed compositions containing both natural and synthetic chelating reagents:citrate and ethylenediaminetetraacetate ions as well as an antibiotic. Description of the chemolytic irrigation, numerical results and their possible clinical application are the main topic of the present research. PMID- 22089057 TI - Mycophenolate mofetil inducing remission of lupus enteritis. AB - We report the case of a young woman with a background history of discoid lupus who presented with abdominal pain, vomiting and intermittent diarrhoea. Physical examination revealed tenderness in the right upper quadrant with a palpable right inguinal lymph node without any other clinical signs of active lupus. Laboratory investigations showed normal inflammatory markers, positive ANA and Anti-Ro antibodies, persistent hypocomplementemia and lymphopenia, CT showed marked bowel oedema involving the small and large bowel (halo sign) with massive ascites and moderate right-sided pleural effusion. Mantoux test, AFB and TB cultures were negative. A diagnosis of lupus enteritis was made and treatment with high-dose steroids was commenced with little improvement. Treatment with cyclophosphamide was discussed but declined by the patient. Mycophenolate mofetil was commenced and resulted in significant clinical and radiological resolution. To the best of the authors' knowledge this is the first report of the successful use of mycophenolate mofetil in inducing and maintaining remission in lupus enteritis. PMID- 22089058 TI - Association of galectin-3 and fibrosis markers with long-term cardiovascular outcomes in patients with heart failure, left ventricular dysfunction, and dyssynchrony: insights from the CARE-HF (Cardiac Resynchronization in Heart Failure) trial. AB - AIMS: Circulating biomarkers of collagen turnover reflect extracellular cardiac matrix (ECCM) remodelling. The extent to which the success of cardiac resynchronization therapy (CRT) is influenced by the degree of cardiac fibrosis and whether CRT can influence matrix remodelling has yet to be studied. Our aim was to determine, in patients with heart failure (HF) and cardiac dyssynchrony, whether ECCM biomarkers are influenced by CRT and can predict cardiovascular outcomes and response to CRT. METHODS AND RESULTS: Serum levels of ECCM biomarkers [galectin-3 (Gal-3), N-terminal propeptides of type I and III procollagens (PINP and PIIINP), type I collagen telopeptide (ICTP), and matrix metalloproteinase 1 (MMP-1)] were measured in 260 patients, in a substudy of CARE HF, a randomized controlled trial which evaluated the effects of CRT in patients with left ventricular systolic dysfunction and cardiac dyssynchrony. ECCM biomarkers did not change throughout the 18-month follow-up period. In age- and gender-adjusted analyses, Gal-3 and PIIINP were associated with death or HF hospitalization. In a further multivariate model, Gal-3 >30 ng/mL was associated [OR (95% CI):2.98 (1.43-6.22), P = 0.004] with death or HF hospitalization, along with left ventricular end-systolic volume >200 mL [3.42 (OR: 1.65-7.10), P = 0.001]. The outcome death or left ventricular ejection fraction (LVEF) <=35% was associated with MMP-1 [<=3 ng/mL: 3.04 (1.37-6.71), P = 0.006]. No significant interaction was observed between the tested biomarkers and the treatment group. CONCLUSIONS: Increased Gal-3 and PIIINP, and low MMP-1 are associated with adverse long-term cardiovascular outcomes but did not predict response to CRT. CRT did not favourably affect serum concentrations of ECCM markers. PMID- 22089059 TI - Genome-wide association studies (GWAS) in complex diseases: advantages and limitations. PMID- 22089060 TI - [Transitional care programs for patients with rheumatic diseases: review of the literature]. AB - Transitional care programs are developed to facilitate the passage of a young patient with a chronic disease to an adult clinic where he needs to learn how to get involved in his own care. Various models have been proposed to address this transition in a multidisciplinary process. This review will address, in an updated format, various aspects of the transition units. With this objective in mind, we developed a narrative overview of the available information in the literature on transition units (TU) in rheumatic diseases. The most relevant information is presented in different stages: description and recommendations for the management of the adolescent patient, guidelines and information on programs at TU, and a description of aspects that should be part of a TU. Although several transition programs have been described, we do not have enough information to know what the ideal one would be like. More research is needed in this field, focusing on variables such as quality of life, satisfaction, activity and chronic damage. PMID- 22089061 TI - Cryoglobulinemia with acronecrosis not associated with hepatitis C infection: a case report. AB - Cryoglobulinemia is a rare disease characterized by the production of monoclonal or polyclonal immunoglobulins that precipitate in cold temperature. While this phenomenon can be observed in a large number of disorders, it has been associated with hepatitis C virus infection in more than 90% of cases. The remaining 10%, called essential cryoglobulinemia, has been characterized by a more severe course and a failure to respond to conventional treatment. This article describes the case of a patient with essential cryoglobulinemia presenting with acronecrosis with a poor outcome, despite treatment, leading to amputation. PMID- 22089062 TI - Treating rheumatoid arthritis to target: evidence-based recommendations for enhanced disease management. PMID- 22089063 TI - Compressive myelopathy as the presentation form of a transdiscal fracture of the vertebrae in a patient with ankylosing spondylitis. PMID- 22089064 TI - Premenopausal osteoporosis: how to treat? AB - There is no agreement in defining osteoporosis in premenopausal women and diagnosis must be done carefully and not based on densitometric parameters. One must take into account the presence of other risk factors and history of fragility fractures, diseases or drugs that cause bone loss. Over 50% of premenopausal women with osteoporosis will have a secondary cause, with the remainder diagnosed with idiopathic osteoporosis. Therapeutic considerations are limited by a few studies in this group of patients, especially in regard to the risk of fractures. On the other hand, the FRAX index cannot be applied to premenopausal women. This article will review the measures to apply depending on the type of premenopausal osteoporosis, based on current scientific evidence. PMID- 22089065 TI - Biochemical markers in osteoporosis: usefulness in clinical practice. AB - Currently, the measurement of bone remodeling biomarkers is an innovate proposal in clinical evaluation of patients with osteoporosis. Its use may identify patients at increased risk of fracture as well as monitoring therapeutic efficacy. Because they constitute a relatively inexpensive non-invasive measurement, its use should be widespread for serial and frequent measurements of bone turnover. However, their analytical and biological variability limits their clinical applicability. PMID- 22089066 TI - Hyperparathyroidism: primary or secondary disease? AB - Primary hyperparathyroidism (PHPT) is characterized by the autonomous production of parathyroid hormone (PTH), in which there is hypercalcemia or normal-high serum calcium levels in the presence of elevated or inappropriately normal serum PTH concentrations. Exceptionally in symptomatic patients, a diagnostic can be established on the basis of clinical data. PHPT must always be evaluated in patients with clinical histories of nephrolithiasis, nephrocalcinosis, osseous pain, subperiosteal resorption, and pathologic fractures, as well as in those with osteoporosis-osteopenia, a personal history of neck irradiation, or a family history of multiple endocrine neoplasia syndrome (types 1 or 2). Diagnosis of PHPT is biochemical. Asymptomatic hypercalcemia without guiding signs or symptoms is the most frequent manifestation of the disease. For differential diagnosis, PTH must be measured, as well as phosphate, chloride, 25-hydroxyvitamin D, 1,25 dyhidroxyvitamin D and calcium-to-creatinine clearance. The diagnosis and differential diagnosis of primary hyperparathyroidism will be discussed here. PMID- 22089067 TI - Remmiting symmetric seronegative synovitis with pitting edema (RS3PE). PMID- 22089069 TI - ? PMID- 22089068 TI - Septic arthritis due to Fusobacterium nucleatum in an immunocompetent patient. PMID- 22089070 TI - [Granulomatosis with polyangiitis (Wegener). Description of 15 cases]. AB - BACKGROUND: Granulomatosis with polyangiitis (GP) is a necrotizing vasculitis of unknown etiology that involves small and medium caliber vessels. It is associated with anti neutrophil cytoplasm antibodies (ANCA). It most often affects the respiratory tract and the kidneys and its most important pathologic feature is the presence of necrotizing granulomas. OBJECTIVES: To detail the features of 15 patients with GP diagnosed in a university referral center. PATIENTS AND METHODS: Retrospective study: between 1984 and 2009, 15 patients with GP were diagnosed in our center. Epidemiological, clinical, laboratory test as well as pathologic studies and treatment were retrospectively analyzed. Biopsy diagnosis of GP was considered as an inclusion criterion. RESULTS: Fifteen patients were diagnosed: 12 men and 3 women. Mean age at diagnosis: 52.2 years (14-78). 12 patients had a history of smoking. A biopsy was diagnostic in all patients. ANCA were positive in 11 cases, 6 had a cytoplasmic c-ANCA pattern. All patients had pulmonary involvement and seven (40%) had renal involvement. All patients received intravenous glucocorticoids and cyclophosphamide as induction therapy. During the disease progression 5 patients died. CONCLUSIONS: The clinical features of this series do not differ from those described by other authors. However, a history of smoking is more common than expected. Frequently used drugs were glucocorticoids and cyclophosphamide (oral and pulse therapy). The course was usually unfavorable, with outbreaks or complications due to immunosuppression, except for those with limited forms. Immunosuppressive therapy should be maintained indefinitely in most cases. PMID- 22089071 TI - [Vascular changes in severe carpal tunnel syndrome: a differential diagnosis of vasculitis]. AB - Carpal tunnel syndrome may present with skin lesions. This may lead to a differential diagnosis with vasculitis. Sympathetic nervous system perivascular involvement and recurrent injuries secondary to sensory loss are probably part of the mechanism of injury. In this case, we also comment on the pathogenic role of persistent median artery associated with a bifid median nerve. PMID- 22089072 TI - [Crowned Dens syndrome: calcification of the transverse ligament of the atlas]. PMID- 22089073 TI - [How to effectively use methotrexate in rheumatoid arthritis?]. AB - Methotrexate (MTX) is the first choice disease modifying anti-rheumatic drugs for rheumatoid arthritis. In spite of its generalized use by rheumatologists worldwide, there is a general lack of agreement regarding the route of administration, the start-up dose and the way to increase the same. In this article we propose a simplified outline for the use of the drug that should be individualized, based on it's pharmacological aspects, guidelines and recommendations published in high impact factor journals during the past few years. Adverse reactions and side effects, as well as their follow up are also reviewed. PMID- 22089074 TI - [Acute miopericarditis as the presenting feature of adult-onset Still's disease]. AB - Adult Still's disease (ASD) was described by George Still in 1896. ASD is a rare inflammatory disorder, of unknown etiology, whose clinical manifestations are manifold. Diagnosis requires high clinical suspicion and exclusion of different etiologies. We report the case of a 20 year old male with fever, arthritis, dyspnea and chest pain. Laboratory findings showed increased levels of cardiac enzymes, and a pleuropericardic effusion was detected in imaging tests, both of them showing myopericarditis. Corticosteroid treatment was started with initial improvement, although the addition of methotrexate was necessary in the following months. PMID- 22089075 TI - [Gouty arthritis is not everything]. PMID- 22089076 TI - [Trochanteric bursitis due to tuberculosis in an immunocompetent young woman]. AB - Soft tissue infection due to Mycobacterium tuberculosis can affect muscle, tendons, fascia, bursa and synovial tissue. Tuberculous trochanteric bursitis is a rare entity that usually affects immunocompromised patients. Manifestations usually occur insidiously, which delays diagnosis and treatment. We present the case of an immunocompetent young woman who came to our department for chronic left hip pain. The study confirms the diagnosis of tuberculous trochanteric bursitis. This case demonstrates the importance of considering a possible infectious origin of bursitis in immunocompetent patients. PMID- 22089077 TI - Exercise prescription: a case for standardised reporting. AB - BACKGROUND: Structured, regular exercise is recommended to improve health outcomes. Exercise takes many forms and varies in type, intensity, duration and frequency. The authors used the example of exercise for chronic health conditions to examine how exercise programmes are described and summarised in systematic reviews. METHODS: Two independent reviewers conducted a review of exercise reporting practices using the evidence of exercise effects for chronic conditions as the source material. INCLUSION CRITERIA: systematic reviews that summarised the effects of exercise programmes for adults with chronic health conditions. EXCLUSION CRITERIA: reviews of studies of children and adolescent populations, and non-English publications. RESULTS: Seventy-three reviews were included. Data on sample size, number of included trials, interventions, comparisons, programme characteristics, exercise components, author conclusions and recommendations were extracted. Seventy-one per cent of reviews reported being unable to adequately describe the exercise programmes, because the required information was not reported in included trials. Using key exercise descriptors from the included reviews, the authors developed criteria for reporting to a level that enables replication. CONCLUSIONS: All included reviews recommended better and standardised reporting. Incomplete exercise programme descriptions limit confidence in the accurate replication of effective interventions and limits critical appraisal of interventions when conflicting outcomes are reported. The evaluation and implementation of physical activity and exercise research would be facilitated if exercise programmes are comprehensively described. The authors propose that systematic reviews/meta-analysis and clinical application of the outcomes of exercise therapy research would be enhanced if authors used an exercise reporting grid that includes a detailed description of the programme components. PMID- 22089078 TI - A systematic review of patient-reported outcome measures used to assess Achilles tendon rupture management: what's being used and should we be using it? AB - BACKGROUND: Currently, there is no consensus regarding the optimal management for patients following an Achilles tendon rupture. To allow comparisons between different treatments, a universally accepted outcome measure is required. However, there are currently a range of these reported within the literature. OBJECTIVE: To recommend the most suitable patient-reported outcome measure for the assessment of patients following an Achilles tendon rupture, based on a systematic review of first what is currently used and second evidence of validity. METHODS: The electronic databases MEDLINE, EMBASE and AMED were searched up to September 2010. Predefined inclusion and exclusion criteria were applied to identify what outcome measures are reported in the literature. Aspects of validity were defined and a checklist used to determine which aspects have been evaluated. RESULTS: Twenty-one outcome measures in 50 research papers were identified. The most commonly used was the American Orthopaedic Foot and Ankle Society hind-foot score. Of the 21 outcome measures, only 4 cited independent validation data. Of these four, only the 'Achilles tendon Total Rupture Score' reported evidence to support multiple facets of validity, as defined by a predetermined criteria checklist. CONCLUSIONS: The Achilles tendon Total Rupture Score was identified as the only outcome measure which has demonstrated multiple facets of validity for use in this patient group. However, even this tool has limitations. Researchers should be aware of the limitations of the available outcome measurement tools and check on their validity before use in clinical research. PMID- 22089079 TI - The impact of dementia on influenza vaccination uptake in community and care home residents. AB - BACKGROUND: Influenza vaccination is recommended for older people irrespective of cognitive decline or residential setting. OBJECTIVE: To examine the effect of dementia diagnosis on flu vaccination uptake in community and care home residents in England and Wales. METHODS: Retrospective analysis of a primary care database with 378,462 community and 9,106 care (nursing and residential) home residents aged 65-104 in 2008-09. Predictors of vaccine uptake were examined adjusted for age, sex, area deprivation and major chronic diseases. RESULTS: Age and sex standardised uptake of influenza vaccine was 74.7% (95% CI: 73.7-75.8%) in community patients without dementia, 71.4% (69.3-73.5%) in community patients with dementia, 80.5% (78.9-82.2%) in care home patients without dementia and 83.3% (81.4-85.3%) in care home patients with dementia. In a fully adjusted model, compared with community patients without dementia, patients with dementia in the community were less likely to receive vaccination (RR: 0.96, 95% CI: 0.94 0.97) while care home patients with (RR: 1.06, 1.03-1.09) and without (RR: 1.03, 1.01-1.05) dementia were more likely to receive vaccination. Area deprivation and chronic diseases were, respectively, negative and positive predictors of uptake. CONCLUSION: Lower influenza vaccine uptake among community patients with dementia, compared with care home residents, suggests organisational barriers to community uptake but high uptake among patients with dementia in care homes does not suggest concern over informed consent acts as a barrier. Primary care for community patients with dementia needs to ensure that they receive all appropriate preventive interventions. PMID- 22089080 TI - Platypnoea-orthodeoxia in an elderly man with patent foramen ovale and dilated ascending aorta. AB - We report the case of an 85-year-old male with platypnoea-orthodeoxia associated with patent foramen ovale (PFO) and ectatic ascending aorta, in the absence of any significant pulmonary pathology. PMID- 22089081 TI - Comparison of ABCD2 scoring between first healthcare-contact and stroke specialist physicians for transient ischaemic attack in a rapid-access clinic. PMID- 22089082 TI - The impact of dementia on care transitions during the last two years of life. AB - BACKGROUND: Dementia is one of the main challenges to our health and social care. This study compares the number and timing of transitions between care settings in the last 2 years of life among older people with and without dementia. METHODS: Data were derived from Finnish national registers, and include all those who died in 2002 and 2003 at the age of 70 or older (n = 70,366). Negative binomial regression analyses were used to analyse the impact of dementia on number of transitions among people with and without dementia and to adjust the number for age, gender and other diagnoses. RESULTS: In the group that lived at home 2 years before death people with a dementia diagnosis had 32% more care transitions than people without dementia, while the group that was in residential care facility 2 years before death people with dementia had 12% fewer moves than those without dementia The average number of transition was highest in last 3 months of life. People with dementia had their last move more often between care facilities and hospitals offering basic health care than people without dementia. CONCLUSION: Dementia has a significant impact on the number and type of transitions. As the number of people with dementia increases, the quality and equity of care of these patients in their last years constitute a special challenge. PMID- 22089083 TI - Photic induction of locomotor activity is correlated with photic habitat in Anolis lizards. AB - A variety of ecologically important behaviors, including circadian rhythms and seasonal reproduction, are influenced by non-visual responses to light, yet very little is known about the relationship between photic habitat and non-visual photoreception. Puerto Rican Anolis lizards have diverged into multiple photic niches, making them a good model for non-visual photosensory ecology. We investigated the photic induction of locomotor activity, a non-visual response to light, in four species of Anolis comprising two pairs of closely related, ecomorphologically similar species whose microhabitats differ in solar irradiance. We developed a device for continuous, automated detection and recording of anole locomotor activity, and used it to characterize activity under 12:12 h light-dark cycles. Next, we administered a series of 2-h light pulses during the dark period of the light-dark cycle and measured the increase in locomotor activity relative to baseline dark activity. Five different irradiances (ranging from very dim to daytime levels) were given to each individual lizard on separate nights. As expected, light caused an irradiance-dependent increase in locomotor activity in all four species. The responses at the highest irradiances were significantly greater in species occupying relatively more shaded habitats, suggesting that non-visual photoreception may be adapted to habitat light in Anolis lizards. PMID- 22089084 TI - Estimation of the secondary cancer risk induced by diagnostic imaging radiation during proton therapy. AB - We have estimated the secondary cancer risk (SCR) introduced by image-guided procedures during proton therapy. The physical dose from imaging radiation and the corresponding organ equivalent dose were calculated for the case of a lumbar spine patient. The maximum physical dose delivered to the patient during the imaging procedure was estimated to be ~0.35% of the prescribed dose of 46 Gy. However, this small imaging dose substantially raised the radiation-induced SCR by ~8%. In addition, the clinical benefit (improved accuracy during the procedure) and costs (extra SCR) associated with image-guided procedures were quantitatively modelled by systematically investigating the changes in SCR as a function of the prescribed dose, treatment target volume and imaging field size. The results showed that the SCR varied sensitively with the volume receiving the imaging and the therapeutic radiation, whereas the SCR depended to a lesser extent on the magnitude of the applied therapeutic radiation. These results showed that the additional SCR introduced by imaging radiation could be efficiently reduced by minimizing the imaging field size during image-guided procedures. PMID- 22089085 TI - Proctophantastes nettastomatis (Digenea: Zoogonidae) from Vanuatu deep-sea fish: new morphological features, allometric growth, and phenotypic plasticity aspects. AB - The present paper deals with Proctophantastes nettastomatis (Digenea: Zoogonidae; Lepidophyllinae) found in the intestine of three species of deep-sea fish, Dicrolene longimana (Ophidiidae, Ophidiiformes), Bathyuroconger sp. (Congridae, Anguilliformes), and Venefica tentaculata (Nettastomatidae, Anguilliformes). The fish were collected near the islands of Espiritu Santo, Erromango, and Epi, respectively, in the archipelago of Vanuatu (Southern Pacific Ocean) at depths ranging from 561 to 990 m. Morphological and histological analyses showed that the Vanuatu specimens differ from Proctophantastes abyssorum, Proctophantastes gillissi, Proctophantastes glandulosum, Proctophantastes infundibulum, and Proctophantastes brayi but are close to P. nettastomatis discovered in Suruga Bay, Japan. P. nettastomatis is redescribed based both on the observations of our specimens and of the Japanese holotype and paratype. The morphological variability of the species is described. Morphometric data allowed the identification of positive allometric growth for the hindbody, negative allometric growth for the ventral sucker, and a growth phenotypic plasticity between Ophidiiformes and Anguilliformes definitive hosts. PMID- 22089086 TI - Larvicidal activity of silver nanoparticles synthesized using Plumeria rubra plant latex against Aedes aegypti and Anopheles stephensi. AB - In the present study activity of silver nanoparticles (AgNPs) synthesized using Plumeria rubra plant latex against second and fourth larval instar of Aedes aegypti and Anopheles stephensi was determined. Range of concentrations of synthesized AgNps (10, 5, 2.5, 1.25, 0.625, 0.3125 ppm) and aqueous crude latex (1,000, 500, 250, 125, 62.50, 31.25 ppm) were tested against larvae of A. aegypti and A. Stephensi. The synthesized AgNps from P. rubra latex were highly toxic than crude latex extract in both mosquito species. The LC(50) values for second and fourth larval instars after 24 h of crude latex exposure were 1.49, 1.82 ppm against A. aegypti and 1.10, 1.74 ppm against A. stephensi respectively. These figures were 181.67, 287.49 ppm against A. aegypti and 143.69, 170.58 ppm against A. stephensi respectively for crude latex extract. The mortality rates were positively correlated with the concentration of AgNPs. The characterization studies of synthesized AgNPs by UV-Vis spectrophotometry, transmission electron microscopy (TEM), Particle size analysis (PSA) and zeta potential confirmed the spherical shape and size (32-200 nm) of silver nanoparticles along with stability. Toxicity studies carried out against non-target fish species Poecilia reticulata, the most common organism in the habitats of A. aegypti and A. stephensi showed no toxicity at LC(50) and LC(90) doses of the AgNPs. This is the first report on mosquito larvicidal activity of latex synthesized nanoparticles. PMID- 22089087 TI - In vitro induction of anterior gradient-2-specific cytotoxic T lymphocytes by dendritic cells transduced with recombinant adenoviruses as a potential therapy for colorectal cancer. AB - Anterior gradient-2 (AGR2) promotes tumor growth, cell migration, and cellular transformation, and is one of the specific mRNA markers for circulating tumor cells in patients with gastrointestinal cancer. We investigated the feasibility of AGR2 as a potent antigen for tumor immunotherapy against colorectal cancer (CRC) cells using dendritic cells (DCs) transduced with a recombinant adenovirus harboring the AGR2 gene (AdAGR2). DCs transduced with a recombinant adenovirus encoding the AGR2 gene (AdAGR2/DCs) were characterized. These genetically modified DCs expressed AGR2 mRNA as well as AGR2 protein at a multiplicity of infection of 1,000 without any significant alterations in DC viability and cytokine secretion (IL-10 and IL-12p70) compared with unmodified DCs as a control. In addition, AdAGR2 transduction did not impair DC maturation, but enhanced expression of HLA-DR, CD80, and CD86. AdAGR2/DCs augmented the number of IFN-gamma-secreting T-cells and elicited potent AGR2-specific cytotoxic T lymphocytes capable of lysing AGR2-expressing CRC cell lines. These results suggest that AGR2 act as a potentially important antigen for immunotherapy against CRC in clinical applications. PMID- 22089089 TI - Identification of novel peptides that stimulate human neutrophils. AB - Neutrophils play a key role in innate immunity, and the identification of new stimuli that stimulate neutrophil activity is a very important issue. In this study, we identified three novel peptides by screening a synthetic hexapeptide combinatorial library. The identified peptides GMMWAI, MMHWAM, and MMHWFM caused an increase in intracellular Ca2+ in a concentration-dependent manner via phospholipase C activity in human neutrophils. The three peptides acted specifically on neutrophils and monocytes and not on other non-leukocytic cells. As a physiological characteristic of the peptides, we observed that the three peptides induced chemotactic migration of neutrophils as well as stimulated superoxide anion production. Studying receptor specificity, we observed that two of the peptides (GMMWAI and MMHWFM) acted on formyl peptide receptor (FPR)1 while the other peptide (MMHWAM) acted on FPR2. Since the three novel peptides were specific agonists for FPR1 or FPR2, they might be useful tools to study FPR1- or FPR2-mediated immune response and signaling. PMID- 22089088 TI - Genetic association of the EGR2 gene with bipolar disorder in Korea. AB - The early growth response gene 2 (EGR2) is located at chromosome 10q21, one of the susceptibility loci in bipolar disorder (BD). EGR2 is involved in cognitive function, myelination, and signal transduction related to neuregulin-ErbB receptor, Bcl-2 family proteins, and brain-derived neurotrophic factor. This study investigated the genetic association of the EGR2 gene with BD and schizophrenia (SPR) in Korea. In 946 subjects (350 healthy controls, 352 patients with BD, and 244 with SPR), nine single nucleotide polymorphisms (SNPs) in the EGR2 gene region were genotyped. Five SNPs showed nominally significant allelic associations with BD (rs2295814, rs61865882, rs10995315, rs2297488, and rs2297489), and the positive associations of all except rs2297488 remained significant after multiple testing correction. Linkage disequilibrium structure analysis revealed two haplotype blocks. Among the common identified haplotypes (frequency > 5%), 'T-G-A-C-T (block 1)' and 'A-A-G-C (block 2)' haplotypes were over-represented, while 'C-G-G-T-T (block 1)' haplotype was under-represented in BD. In contrast, no significant associations were found with SPR. Although an extended analysis with a larger sample size or independent replication is required, these findings suggest a genetic association of EGR2 with BD. Combined with a plausible biological function of EGR2, the EGR2 gene is a possible susceptibility gene in BD. PMID- 22089090 TI - Fluorinated liquid crystals: design of soft nanostructures and increased complexity of self-assembly by perfluorinated segments. AB - The effects of perfluorinated and semiperfluorinated hydrocarbon units on the self-assembly of rod-like, disc-like, polycatenar, taper- and star-shaped, dendritic, and bent-core liquid crystalline (LC) materials is reviewed. The influence of fluorinated segments is analyzed on the basis of their contributions to the cohesive energy density, molecular shape, conformational flexibility, micro-segregation, space filling, and interface curvature. Though the focus is on recent progress in the last decade, previous main contributions, general aspects of perfluorinated organic molecules, and the basics of LC self-assembly are also briefly discussed to provide a complete overall picture. The main focus is on structure-property-relations and the use of micro-segregation to tailor mesophase morphologies. Especially polyphilic molecules with perfluorinated segments provide new modes of LC self-assembly, leading to ordered fluids with periodic multi-compartment structures and enhanced complexity compared to previously known systems. PMID- 22089091 TI - Living in a cage is a restricted privilege. AB - There exist molecules, whose shape is reminiscent of a cage, that are able to include either metal ions or anions or both. In contrast to what happens in the macroscopic world, where a kinetic barrier prevents the escaping of the guest from the cage, the inclusion-extrusion of an ion from a molecular cage is in most cases thermodynamically controlled and the ion can get in or out of the cage at will. This gives the basis for highly selective ion recognition processes by cage shaped ligands or receptors for metal ions and anions. Nobody in everyday life would say that a cage (for birds or wild animals), even if nicely designed and splendidly decorated, was beautiful and appealing, due to the consciousness of its reprehensible function. This does not happen in chemistry and we admire the ingenuity and skilfulness of synthetic chemists for the design of cage-shaped polycyclic hosts, made for the inclusion of a variety of guests, but also capable of generating in the viewer emotion and gratification of aesthetical origin. We have tried to outline, in this chapter, the development of cages in metal coordination chemistry and in anion coordination chemistry, over the last 50 years. PMID- 22089092 TI - Neighborhood disorder and children's antisocial behavior: the protective effect of family support among Mexican American and African American Families. AB - Using data from a sample of 673 Mexican Origin families, the current investigation examined the degree to which family supportiveness acted as a protective buffer between neighborhood disorder and antisocial behavior during late childhood (i.e. intent to use controlled substances, externalizing, and association with deviant peers). Children's perceptions of neighborhood disorder fully mediated associations between census and observer measures of neighborhood disorder and their antisocial behavior. Family support buffered children from the higher rates of antisocial behavior generally associated with living in disorderly neighborhoods. An additional goal of the current study was to replicate these findings in a second sample of 897 African American families, and that replication was successful. These findings suggest that family support may play a protective role for children living in dangerous or disadvantaged neighborhoods. They also suggest that neighborhood interventions should consider several points of entry including structural changes, resident perceptions of their neighborhood and family support. PMID- 22089093 TI - Pathogenesis of ANCA-associated vasculitis: recent insights from animal models. AB - PURPOSE OF REVIEW: To provide an update on animal models of antineutrophil cytoplasmic autoantibody (ANCA)-mediated vasculitis and highlight recent insights gained from studies in these models pertaining to immunopathogenesis. RECENT FINDINGS: Animal models support the pathogenic potential of myeloperoxidase (MPO) ANCA. Alternative pathway complement activation has been identified as a novel inflammatory pathway in disease induction and a potential target for intervention. Interventions targeting B cells, antibodies, and signal transduction pathways may hold promise as well. The role of T cells is beginning to be explored, and studies indicate a prominent role for Th17 responses. The link between infection and ANCA vasculitis is well established. In animal models, Toll-like receptor (TLR)4 ligation is involved in disease induction. Ligation of TLRs contributes to the initiation of anti-MPO autoimmune responses in which TLR2 activation induces a Th17 response and TLR9 activation directs a Th1 response. An animal model for PR3-ANCA vasculitis is not available yet but models with a humanized immune system are being developed and show promising first results. SUMMARY: Animal models of MPO-ANCA vasculitis have contributed substantially to our understanding of disease immunopathogenesis and have illuminated novel targets for intervention. The development of PR3-ANCA animal models remains a challenge but recent observations in humanized model systems offer hope. PMID- 22089094 TI - Animal models of antineutrophil cytoplasm antibody-associated vasculitis. AB - PURPOSE OF REVIEW: To provide an update on the experimental models that have been developed recapitulating clinical antineutrophil cytoplasm antibody (ANCA) associated vasculitis. The application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue. RECENT FINDINGS: Rodent models of both myeloperoxidase (MPO) ANCA and proteinase 3 (PR3) ANCA associated vasculitis have been developed, which have provided important insights into the pathogenesis of ANCA-associated pulmonary and renal disease. The vast majority of in-vivo work in this field has concerned MPO-ANCA associated disease, although the last year has seen some advances in the modelling of anti-PR3 disease. As with all experimental animal models, they are flawed in one way or another by virtue of the means by which they are induced, but they have already provided novel directions for future intervention in these complex diseases. To date, there are no good models that replicate the granulomatous lesions found in granulomatosis with polyangiitis (GPA, formerly Wegener's) or the development of vasculitis lesions in organs other than the lungs or kidneys. SUMMARY: ANCA associated vasculitis can be induced in various forms in susceptible rodents. Further refinements are required for the full spectrum of disease phenotype to be replicated in animals, but critical new targets have been proposed based on the use of molecular blocking agents and transgenic animals to elucidate disease pathways. PMID- 22089095 TI - Treatment of antineutrophil cytoplasmic antibody-associated vasculitis with rituximab. AB - PURPOSE OF REVIEW: To review the present knowledge about the use of rituximab (RTX) in patients with granulomatosis with polyangiitis (Wegener's; GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss; EGPA), also collectively referred to as antineutrophil cytoplasmic antibody-associated vasculitis. RECENT FINDINGS: More than 20 case series and cohort studies involving more than 200 patients focusing on RTX use for patients with refractory GPA and MPA have been reported. Two randomized controlled trials have shown that RTX is not inferior to cyclophosphamide (CYC) for induction of remission in severe GPA and MPA. The RAVE trial has further shown that RTX is superior to CYC for patients with severe disease relapses. In addition, reports are emerging on the use of RTX for remission maintenance in chronically relapsing patients. There are also preliminary reports on the beneficial use of RTX in eosinophilic granulomatosis with polyangiitis (Churg Strauss). SUMMARY: RTX is the first proven alternative to CYC for remission induction in severe GPA and MPA. RTX is the preferred agent for patients presenting with severe disease flares, and its use had become the de facto standard of care for patients with chronically relapsing refractory GPA. Its use in EGPA requires further investigation. PMID- 22089096 TI - Updating single-organ vasculitis. AB - PURPOSE OF REVIEW: To clearly define single-organ vasculitis (SOV) and distinguish diffuse from focal SOV. To delineate clinical, laboratory, and histopathological features useful in differentiating focal SOV from systemic vasculitis affecting the same territory. RECENT FINDINGS: SOV may affect organs in a diffuse or multifocal fashion (e.g. central nervous system and skin) or may be confined to focal sites (e.g. breast, gynecologic, testicular, and abdominal structures, and the aorta). Because the territories affected in SOV may also be targeted in systemic vasculitis, the diagnosis of SOV should be applied when it is clear that vascular inflammation is not present in other sites at the time of diagnosis as well as during follow-up surveillance, which has arbitrarily been recommended to be of at least 6 months. Once the diagnosis of SOV is confirmed, terms used for systemic vasculitides should be avoided (e.g. polyarteritis of the testes). Focal SOV is often incidentally found in the course of biopsies or surgery for suspected malignancy, infection, or structural abnormalities. In focal SOV, resection of the inflammatory lesion alone may be curative, whereas systemic therapy is almost always required for diffuse forms of SOV. SUMMARY: SOV definition implies vascular inflammation confined to an isolated organ. This diagnosis always requires exclusion of systemic illness. In focal forms of SOV, certain clinical, laboratory, and pathologic features assist the clinician in distinguishing isolated from systemic vasculitis, and consequently in devising therapeutic and surveillance strategies. PMID- 22089097 TI - Churg-Strauss syndrome: update on pathophysiology and treatment. AB - PURPOSE OF REVIEW: Churg-Strauss syndrome (CSS) has a clear clinical phenotype but its pathogenesis is not fully elucidated. Recent studies have focused on its immunogenetic aspects and cytokine and chemokine-mediated pathogenetic mechanisms, providing the rationale for the use of newer targeted therapies. This study will review recent findings on the pathogenesis of CSS and its therapeutic approaches. RECENT FINDINGS: CSS is usually considered a Th2-mediated disease, but Th1 and Th17 responses might also play a role; the reported association between CSS and HLA-DRB4 further underlines the pathogenetic relevance of CD4 T cells which, thanks to their ability to secrete cytokines such as IL4, IL5, and IL13, promote allergic and eosinophilic reactions. Resident cells such as endothelial and epithelial cells might also amplify the immune response by producing eosinophil-attracting chemokines such as eotaxin-3 and CCL17. Conventional immunosuppressive therapies offer high chances of achieving sustained remission, but steroid exposure remains high. Targeting IL5 with mepolizumab seems promising in sparing steroids, but relapses often follow its withdrawal. B-cell depletion using rituximab has proved effective in refractory CSS cases. SUMMARY: Current knowledge on CSS pathogenesis is evolving; the identification of key molecular mechanisms will pave the way for newer, more specific treatments. PMID- 22089098 TI - Erdheim-Chester disease. AB - PURPOSE OF REVIEW: Erdheim-Chester disease (ECD) is a rare, non-Langerhans form of histiocytosis first described in 1930 with a wide range of manifestations. The number of new cases has dramatically increased over the past 10 years because of the better recognition of this condition. The natural evolution is variable, but the spontaneous prognosis is severe. In this review, we describe the relevant clinical, radiological, prognostic, and therapeutic features of this orphan disease. RECENT FINDINGS: Compelling evidence demonstrates the efficacy of treatment by interferon alpha (IFNalpha) which has been reported to be a major independent predictor of survival among ECD patients. Alternative treatments remain to be defined. Recent studies have highlighted the central nervous system involvement as an independent predictor of death. Pathophysiology is better understood with a complex network of cytokines and chemokines and a systemic immune Th-1-oriented perturbation. SUMMARY: ECD, although a rare and orphan disease, has been overlooked and numerous new cases are currently diagnosed because of general better knowledge of this histiocytosis. First-line treatment is IFNalpha. We have recently described a unique cytokine signature that may provide further clues to understand the pathogenesis of ECD, as well as provide new tools for diagnosis and targeted therapy. PMID- 22089099 TI - Biologic treatment of large-vessel vasculitides. AB - PURPOSE OF REVIEW: Glucocorticoids are the mainstay of therapy for giant cell arteritis (GCA) and Takayasu's arteritis. However, a significant proportion of patients have a glucocorticoid-dependent or resistant disease course and serious adverse events are frequent. This article summarizes the current evidence on the use of biologic treatments in large-vessel vasculitis (LVV). RECENT FINDINGS: Antitumour necrosis factor (TNF) treatment strategies have failed to show efficacy in GCA, whereas their role in Takayasu's arteritis is yet unclear. Preliminary reports on the use of the anti-interleukin-6 receptor antibody tocilizumab (TOC) in both GCA and Takayasu's arteritis emerge. TOC was both able to spare glucocorticoid doses but could also induce remission in untreated GCA patients when used as monotherapy. There is little evidence for the use of biologic drugs in LVV associated with systemic rheumatic diseases. Case series suggest efficacy for anti-TNF antibodies in aortitis associated with relapsing polychondritis and pulmonary artery aneurysm associated with Behcet's disease. SUMMARY: TNF inhibition does not seem to save glucocorticoids or prevent relapses in GCA. Blocking TNF may provide benefit to difficult-to-treat patients with Takayasu's arteritis, relapsing polychondritis and Behcet's disease-associated LVV. Emerging reports on the use of TOC suggest an important role of IL-6 in the pathogenesis of large-vessel vasculitides and deserve further investigation. The use of TOC monotherapy to induce remission in untreated GCA patients proves fascinating. PMID- 22089100 TI - Familial Mediterranean fever and related periodic fever syndromes/autoinflammatory diseases. AB - PURPOSE OF REVIEW: The spectrum of periodic fever syndromes (PFS)/autoinflammation diseases is continuously expanding. This review provides an overview of the primary research and an update on the main clinical developments in these disorders published in the past 12-18 months. RECENT FINDINGS: IL-1beta is pivotal to the pathogenesis of most of the PFS. In familial Mediterranean fever (FMF) MEFV mutations lead to gain of pyrin function, resulting in inappropriate IL-1beta release that is dependent on ASC but not the NLRP3 inflammasome. Anti-IL-1 therapy is effective in tumour necrosis factor receptor-associated periodic syndrome (TRAPS), whilst both spontaneous and pathogen-associated molecular patterns (PAMPs) induced IL-1beta release have been demonstrated in NLRP12-associated periodic syndrome (NAPS12). Somatic NLRP3/CIAS1 mosaicism is a significant cause of cryopyrin-associated periodic syndromes (CAPS). Close connections have also been established between metabolic and inflammatory pathways. In TRAPS increased reactive oxygen species (ROS) of mitochondrial origin leads to production of pro-inflammatory cytokines, whilst NLRP3 inflammasome activation in type 2 diabetes (T2D) is induced by oligomers of islet amyloid polypeptides (IAPP). SUMMARY: Caspase 1 activation and IL-1beta release is central to the pathogenesis of many autoinflammatory syndromes. This is supported by the effectiveness of anti-IL-1 biologics in treatment of these disorders. PMID- 22089101 TI - Not all hemophagocytes are created equally: appreciating the heterogeneity of the hemophagocytic syndromes. AB - PURPOSE OF REVIEW: The deadly macrophage activation syndrome (MAS) constitutes one of the few rheumatologic emergencies. MAS is part of a larger group of diseases referred to as hemophagocytic syndromes that are seen in infections, malignancies, or genetic immunodeficiencies. Because of the clinical similarity of these diseases, many clinicians are tempted to approach them all similarly, both in diagnostic criteria and treatment paradigms. New work in the field suggests that not all hemophagocytic syndromes are equal. We will review the latest literature from both human and murine models related to the diagnosis, etiology, and treatment of hemophagocytic syndromes including MAS. RECENT FINDINGS: More specific diagnostic criteria for the different hemophagocytic syndromes are being developed. Animal models suggest at least two different mechanisms by which hemophagocytic syndromes arise: enhanced antigen presentation and excessive Toll-like receptor signaling. Work in humans suggests different cytokine profiles, and different treatment strategies for the variety of hemophagocytic syndromes. SUMMARY: The recent studies reviewed in this article suggest that despite clinical similarities the different hemophagocytic syndromes are indeed likely heterogeneous. Diagnostic criteria and treatment strategies tailored to the underlying disease or genetic context are needed and will hopefully be addressed by future work in this field. PMID- 22089102 TI - Autoimmune hepatitis: current challenges in diagnosis and management in a chronic progressive liver disease. AB - PURPOSE OF REVIEW: The understanding of autoimmune hepatitis (AIH) has evolved in the past two decades since diagnostic criteria were developed. Now with long-term experience with well characterized cohorts, strides have been gained in understanding the true epidemiology and natural history of the disease. Therapeutic trials have also added new tools to the armamentarium in managing this challenging disease. RECENT FINDINGS: AIH has been demonstrated to be a disease of middle-aged women, with a disease course that frequently progresses to cirrhosis, transplant or death. Despite its rare prevalence, AIH is one of the most common indications for transplantation. Diagnosis remains challenging, and the most recently adopted criteria prove very specific but lack sensitivity in the diagnosis of AIH, particularly when presenting atypically. Recently, drug induced AIH and IgG4-associated AIH have been proposed as distinct clinicopathological entities. Clinical trials for alternate therapeutics have long been needed, and recently two agents, budesonide and mycophenolate mofeteil, show promise in treating AIH. SUMMARY: Increasing evidence has mounted to suggest that AIH is a disease that often requires long-term treatment, and frequently progresses to end-stage liver disease. Further research identifying predictors of poor outcome, optimal therapeutic regimens and duration of treatment is much needed. PMID- 22089103 TI - Blood pressure control in a Japanese population with chronic kidney disease: a baseline survey of a nationwide cohort. AB - BACKGROUND: Hypertension is a key risk factor for adverse renal outcomes in chronic kidney disease (CKD), and strict blood pressure control is recommended to halt its progression. This study assessed blood pressure control in the Japanese CKD population. METHODS: We used a nationwide database of 250,130 subjects (aged 20-88), including 45,845 CKD subjects (18.3%), participated in an annual health check, "The Specific Health Check and Guidance in Japan," and examined the relationship between CKD status and blood pressure. Blood pressures were measured in sitting position by trained staff, and target blood pressure for CKD subjects was defined as systolic (SBP)/diastolic blood pressure (DBP) <130/80 mm Hg. RESULTS: In total population, CKD subjects had a higher prevalence of hypertension (58.0% vs. 41.8%, P < 0.001) and a higher proportion with antihypertensive medication (42.4% vs. 26.7%, P < 0.001), compared with non-CKD subjects. The proportion of subjects achieving target blood pressure was significantly lower among total CKD subjects than among total non-CKD subjects (34.6% vs. 43.8%, P <= 0.001). Among CKD subjects, these proportions were especially low in those with stage 4-5 (24.3-27.5%), those on antihypertensive medication (21.6%) and those with proteinuria >=2+/- (21.3%). Logistic regression analysis showed that independent factors for high-blood pressure in CKD subjects were age, male gender, alcohol consumption, nonsmoking, diabetes, dyslipidemia, obesity, proteinuria, and antihypertensive medication. CONCLUSIONS: Blood pressure control was inadequate in the majority of Japanese CKD subjects, despite antihypertensive treatment. More aggressive efforts to achieve target blood pressures among CKD subjects are recommended. PMID- 22089104 TI - Activation of the mineralocorticoid receptor increases striatin levels. AB - BACKGROUND: Aldosterone (ALDO), a critical regulator of sodium homeostasis, mediates its effects via activation of the mineralocorticoid receptor (MR) through mechanisms that are not entirely clear. Striatin, a membrane associated protein, interacts with estrogen receptors in endothelial cells. METHODS: We studied the effects of MR activation in vitro and in vivo on striatin levels in vascular tissue. RESULTS: We observed that dietary sodium restriction was associated with increased striatin levels in mouse heart and aorta and that striatin and MR are present in the human endothelial cell line, (EA.hy926), and in mouse aortic endothelial cells (MAEC). Further, we show that MR co precipitates with striatin in vascular tissue. Incubation of EA.hy926 cells with ALDO (10(-8) mol/l for 5-24 h) increases striatin protein and mRNA expression, an effect that was inhibited by canrenoic acid, an MR antagonist. Consistent with these observations, incubation of MAEC with ALDO increased striatin levels that were likewise blocked by canrenoic acid. To test the in vivo relevance of these findings, we studied two previously described mouse models of increased ALDO levels. Intraperitoneal ALDO administration augmented the abundance of striatin protein in mouse heart. We also observed that in a murine model of chronic ALDO mediated cardiovascular damage following treatment with N(G)-nitro-L-arginine methyl ester plus angiotensin II an increased abundance of striatin protein in heart and kidney tissue. CONCLUSION: Our results provide evidence that increased striatin levels is a component of MR activation in the vasculature and suggest that regulation of striatin by ALDO may modulate estrogen's nongenomic effects. PMID- 22089105 TI - Blood pressure responses and metabolic effects of hydrochlorothiazide and atenolol. AB - BACKGROUND: Thiazides and beta-blockers cause adverse metabolic effects (AMEs), but whether these effects share predictors with blood pressure (BP) response is unknown. We aimed to determine whether AMEs are correlated with BP response in uncomplicated hypertensives. METHODS: In a multicenter, open-label, parallel group trial, we enrolled 569 persons, aged 17-65, with random assignment to 9 weeks of daily hydrochlorothiazide (HCTZ) or atenolol monotherapy, followed by 9 weeks of add-on therapy with the alternate agent. Measurements included home BP, averaged over 1 week, weight and fasting levels of serum glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and uric acid (UA) before and after monotherapy and after add-on therapy. RESULTS: Increases in UA correlated with reductions in systolic BP (SBP) (r = -0.18; P = 0.003) and diastolic BP (DBP) (r = -0.20; P = 0.001) following HCTZ monotherapy and add-on therapy (r = -0.27 and r = -0.21, respectively; both P < 0.001). After adjustment for age, race, gender, and baseline body mass index (BMI), only the correlation between UA and DBP response became nonsignificant. Reductions in HDL correlated with systolic response following atenolol monotherapy (r = 0.18; P = 0.002) and with systolic and diastolic response following add-on therapy (r = 0.30 and r = 0.24, respectively; both P < 0.0001). These correlations remained significant after covariate adjustment. BP responses were not correlated with changes in glucose, LDL, triglycerides, or weight following either therapy. CONCLUSIONS: BP response correlated with changes in UA following HCTZ therapy and HDL following atenolol therapy. No other significant correlations were observed between BP response and AMEs, suggesting that these effects generally do not share predictors. Patients should be monitored for AMEs, regardless of BP response. PMID- 22089106 TI - Sleep-time blood pressure and the prognostic value of isolated-office and masked hypertension. AB - BACKGROUND: Elevated sleep-time blood pressure (BP) is a better predictor of cardiovascular risk than the awake or 24 h BP means. However, discrepancies in the diagnosis of hypertension between clinic and ambulatory measurements (isolated-office and masked hypertension) are frequently defined by comparing clinic with only awake BP. We evaluated the impact of sleep-time BP in the prognostic value of isolated-office and masked hypertension. METHODS: We studied 3,344 subjects (1,718 men/1,626 women), 52.6 +/- 14.5 years of age, during a median 5.6-years follow-up. Ambulatory BP was measured for 48 h at baseline, and again annually or more frequently (quarterly) after treatment adjustments in hypertensive subjects. RESULTS: Out-of-office (masked and sustained) hypertension was associated with higher cardiovascular risk than normotension and isolated office hypertension (P < 0.001) only when those conditions were defined on the basis of asleep, but not on awake or 24 h BP mean. Using only awake pressure for classification, 58.2% of subjects with masked hypertension were mistakenly classified as normotensive, and 26.3% of subjects with sustained hypertension were erroneously identified as isolated-office hypertensive. Cox proportional hazard analysis using the awake and asleep pressure means as potential predictors of cardiovascular risk and adjusted for significant confounders revealed that only asleep mean was an independent significant predictor of outcome. CONCLUSIONS: Subjects with elevated sleep-time BP are at high cardiovascular risk, independently of either clinic or ambulatory awake measurements. Sleep-time BP determined by ambulatory monitoring should thus be used for proper identification of out-of-office hypertension, a condition associated with markedly increased cardiovascular risk. PMID- 22089107 TI - Agreement between community pharmacy, physician's office, and home blood pressure measurement methods: the PALMERA Study. AB - BACKGROUND: The usefulness of the community pharmacy blood pressure (BP) (CPBP) method in assessing the effectiveness of antihypertensive treatment has not been adequately studied. The aim of this study was to assess the agreement between community pharmacy, home, and physician office BP (POBP) measurement methods in treated hypertensive patients. METHODS: BP was measured at the pharmacy (three visits), at home (4 days) and at the physician office (three visits). The Lin correlation-concordance coefficient (CCC) was used to evaluate the quantitative agreement. The qualitative agreement between methods to establish the patient's hypertensive state was evaluated using the kappa-coefficient. Using home BP (HBP) monitoring as the reference method, the sensitivity, specificity, positive and negative likelihood ratios of the CPBP and POBP measurement methods were calculated. RESULTS: The study included 70 patients. Agreements were acceptable moderate between CPBP and HBP (CCC (systolic BP (SBP)/diastolic BP (DBP)) = 0.79/0.66; kappa = 0.56), moderate between CPBP and POBP (CCC = 0.57/0.61; kappa = 0.35), and moderate-poor (CCC = 0.56/0.49; kappa = 0.28) between POBP and HBP. The sensitivity, specificity, positive and negative likelihood ratio for the CPBP and the POBP measurement methods were: 60.7%, 92.9%, 8.5, 0.4 and 75.0%, 54.8%, 1.7, 0.5, respectively. CONCLUSIONS: In this sample of treated hypertensive patients, the agreement between the community pharmacy and HBP measurement methods was acceptable-moderate and greater than other agreements. The CPBP measurement method was more reliable than the POBP measurement method for detecting the presence of both uncontrolled and controlled BP and could be a good alternative to HBP monitoring when the latter lacks suitability. PMID- 22089108 TI - First-fill medication discontinuations and nonadherence to antihypertensive therapy: an observational study. AB - BACKGROUND: Medication nonadherence is a barrier to successfully managing hypertension, but little is known about the contribution that immediate discontinuations have on antihypertensive (AHT) nonadherence. The purpose of this study was to determine the proportion of new AHT users who discontinue after a single dispensation, and to examine potential predictors of these discontinuations. METHODS: This retrospective cohort study utilizing linked administrative data from Saskatchewan, Canada. Subjects were >=40 years of age and received a new AHT between 1994-2002. The primary end point was the proportion of subjects who discontinued their AHT after the first dispensation (first-fill discontinuation). The proportion of nonadherence attributed to first fill discontinuations was then calculated. Multivariate regression identified factors associated with first-fill discontinuations. RESULTS: 52,039 subjects were included in the analyses. Mean age was 59.4 (s.d. 12.5) years, and 42% were male. Overall, 25,812/52,039 (50%) subjects were nonadherent at 1 year; first fill discontinuations accounted for 39.1% (10,081/25,812) of this nonadherence. Approximately 20% (10,081/52,039) of all subjects discontinued all AHT therapy after the first fill. A higher chronic disease score (adjusted odds ratio (OR) 1.09, 95% confidence interval (CI) 1.08-1.11) and antidepressant medication usage during the observation year (adjusted OR 1.17, 95% CI 1.09-1.26) was associated with increased risk for first-fill discontinuations. Older age, starting AHT therapy after 1994, frequent physician visits, or use of a statin, acetylsalicylic acid, warfarin or antihyperglycemic during the observation year was associated with a lower risk for first-fill discontinuations. CONCLUSION: A substantial proportion of nonadherence to AHT medications is due to discontinuations after only a single dispensation. PMID- 22089109 TI - Qiliqiangxin improves cardiac function in spontaneously hypertensive rats through the inhibition of cardiac chymase. AB - BACKGROUND: This study was designed to investigate the effects and mechanism of action of the traditional Chinese drug formula, qiliqiangxin (QLQX), on cardiac function in spontaneously hypertensive rats (SHRs). METHODS: We evaluated the effects of oral high-dose (4 g/kg/day, n = 7) and low-dose (1 g/kg/day, n = 7) QLQX on cardiac function in SHRs aged between 8 compared to control, the 8-week old Wistar-Kyoto (WKY) rats. Echocardiography was performed to evaluate cardiac function and hemodynamic parameters. Hematoxylin and eosin (HE) and Masson's trichrome staining were performed, and the expression of myocardial angiotensin (Ang)-converting enzyme, chymase, transforming growth factor (TGF)-beta, and collagen-type I and III were evaluated with real-time reverse transcription-PCR. Myocardial chymase, Ang-converting enzyme (ACE), and Ang II activities were measured with radioimmunoassay (RIA) techniques. Cardiac mast cells were detected with toluidine blue staining. RESULTS: In SHRs, the number of chymase enzyme positive mast cells increased in the left ventricle (LV) compared with WKY rats. QLQX significantly decreased mast cell density and cardiac chymase levels, and it improved ejection fraction values and cardiac systolic function compared with vehicle. Moreover, QLQX decreased left atrial diameters and improved the E/A ratio. QLQX suppressed collagen-type I and III and TGF-beta mRNA levels, and Ang II activity, in a dose-dependent manner. Whereas no difference in ACE activity was found between SHRs, chymase expression and activity were significantly decreased with QLQX. CONCLUSIONS: These data suggest that QLQX improves both systolic and diastolic cardiac function in SHRs through downregulating the cardiac chymase signaling pathway and chymase-mediated Ang II production. PMID- 22089110 TI - Control of hypertension in treated children and its association with target organ damage. AB - BACKGROUND: The aim of our study was to investigate the control of hypertension (HT) in treated children using ambulatory blood pressure (BP) monitoring (ABPM). METHODS: We retrospectively reviewed all ABPM studies in our center. Controlled HT was defined as systolic and diastolic BP index (patients' BP divided by the 95th percentile) at daytime and nighttime <1.0 or alternatively as BP load (percentage of BP readings above the 95th percentile) <25% in children on antihypertensive therapy. RESULTS: A total of 195 ABPM studies were included. The mean age was 13.6 +/- 4.0 years. One hundred and thirty two children had renoparenchymal HT, 10 renovascular (RVH), 10 endocrine, 4 cardiovascular, 29 primary (PH) and 5 children other forms of HT. 53% of all children had controlled HT. There was no difference in the prevalence of controlled HT between primary and secondary HT (52% and 53%) using the BP index criterion. Children with renoparenchymal HT had significantly better control of HT than children with RVH (58% vs. 20% P = 0.02). The use of angiotensin-converting enzyme inhibitors (ACEI) monotherapy was significantly more effective in controlling HT than the use of calcium-channel blockers (CCB, P = 0.02). The prevalence of left ventricular hypertrophy in children with uncontrolled HT (assessed in 58 patients) was significantly higher than in children with controlled HT (46% vs. 13%, P < 0.01). CONCLUSIONS: This is the first pediatric study, to our knowledge, on BP control in hypertensive children using ABPM. It indicates that control of HT is inadequate in ~50% of treated children. Inadequate control of HT is associated with target organ damage in this population. PMID- 22089111 TI - Masked hypertension, endothelial dysfunction, and arterial stiffness in type 2 diabetes mellitus: a pilot study. AB - BACKGROUND: The aim of this study was to assess the relationship between masked hypertension (MHT) and vascular damage in patients with type 2 diabetes. METHODS: The study subjects were patients with type 2 diabetes who were normotensive based on blood pressure (BP) measurement in the clinic (n = 80) without antihypertensive drugs and free of retinopathy, macroalbuminuria, overt cardiovascular disease. Subjects underwent 24-h ambulatory blood pressure monitoring (ABPM), measurement of flow-mediated dilatation (FMD), and brachial ankle pulse wave velocity (baPWV). Based on the results of ABPM, subjects with mean daytime systolic BP >=135 and/or 85 mm Hg were defined as MHT and their clinical data were compared with those of normotensive patients (NT). The data were also compared with those of type 2 diabetic patients with hypertension (HT) as measured in the clinic (n = 32). RESULTS: MHT was detected in 47.5% of the study subjects with normotension at clinic (n = 38). Impaired FMD (5.65 +/- 2.00% for NT, 4.26 +/- 1.88% for MHT, 3.90 +/- 1.71% for HT, P < 0.001) and higher baPWV (1,514.2 +/- 212.7 cm/s for NT, 1,749.9 +/- 339.7 cm/s for MHT, and 1,768.6 +/- 302.8 cm/s for HT, P < 0.001) were similarly noted in patients with MHT and HT compared with NT. Multivariate regression analysis indicated that daytime systolic BP measured by ABPM, the estimated duration of diabetes and serum triglycerides were significantly associated with FMD and daytime systolic BP measured by ABPM, not systolic BP at clinic, age, and HbA(1c) were significantly associated with baPWV. CONCLUSIONS: Given that patients with impaired FMD and higher baPWV are known to be at higher risk of cardiovascular disease, our data suggest that type 2 diabetic patients with MHT could be also at increased risk of cardiovascular disease. PMID- 22089112 TI - Role of complement 3a in the synthetic phenotype and angiotensin II-production in vascular smooth muscle cells from spontaneously hypertensive rats. AB - BACKGROUND: Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMCs) show exaggerated growth with a synthetic phenotype and angiotensin II (Ang II)-production. To evaluate the contribution of complement 3 (C3) or C3a toward these abnormalities in SHR, we examined effects of a C3a receptor inhibitor on proliferation, phenotype, and Ang II-production in VSMCs from SHR and Wistar-Kyoto (WKY) rats. METHODS: Expression of pre-pro-C3 messenger RNA (mRNA) and C3 protein was evaluated by reverse transcription-PCR and western blot analyses, and C3a receptor mRNA was evaluated by reverse transcription-PCR analysis in quiescent VSMCs from SHR and WKY rats. We examined the effects of the C3a inhibitor, SB290157, on proliferation and the expression of phenotype-marker and Krueppel-like factor 5 (KLF-5) mRNAs in VSMCs from SHR and WKY rats. We examined effects of C3a receptor inhibitor, SB290157, on Ang II-production in conditioned medium of VSMCs from SHR and WKY rats by a radioimmunoassay. RESULTS: Expression of pre-pro-C3 mRNA and C3 protein was significantly higher in SHR VSMCs than WKY VSMCs. SB290157 significantly inhibited proliferation of VSMCs from SHR, but not in cells from WKY rats. Relative to WKY VSMCs, SB290157 significantly increased the low expression of SM22alpha mRNA and decreased the high expression of osteopontin mRNA in SHR VSMCs. SB290157 significantly decreased the high expression of KLF-5 and Ang II-production in VSMCs from SHR, but not in cells from WKY rats. CONCLUSIONS: C3a induces exaggerated growth, a synthetic phenotype and Ang II-production in SHR-derived VSMCs. C3a may be primarily involved in cardiovascular remodeling in hypertension. PMID- 22089113 TI - GRK2 levels in umbilical arteries of pregnancies complicated by gestational hypertension and preeclampsia. AB - BACKGROUND: G-Protein coupled receptor kinase 2 (GRK2) represents a regulator of cell function in different cardiovascular conditions, including high blood pressure. The relationship between elevated GRK2 levels and impaired vasorelaxant responses is causative of hypertension through the increase in vascular resistances. The aim of this study is to ascertain if this feature is present in the fetal placental vasculature of pregnancies complicated by hypertensive disorders. METHODS: We have assessed GRK2 levels in the umbilical arteries (UA) of 21 preeclamptic or gestational hypertensive and 23 normotensive women at time of delivery. RESULTS: GRK2 levels were increased in the hypertensive group (0.83 +/- 0.14 vs. 0.48 +/- 0.06 densitometry units; P < 0.05). GRK2 levels were in correlation and in linear regression with systolic, diastolic, and mean arterial pressure (P < 0.05, r(2) = 0.12, r(2) = 0.11, r(2) = 0.12). Correlations did not reach a significant value for other clinical parameters such as gestational age at birth, umbilical artery pulsatility index, maternal proteinuria, and neonatal birth weight. Out of the 21 hypertensive women, 7 who developed a preeclampsia associated with early preterm delivery (before 34 weeks) had a significantly lower GRK2 levels compared to the remaining 14 (0.51 +/- 0.12 vs. 1.08 +/- 0.20 densitometry units, P < 0.05). CONCLUSIONS: We conclude that elevated GRK2 levels in the umbilical vasculature is correlated to elevated blood pressure levels, with a likely compensatory rather than causative role since the lack of protective effect of elevated GRK2 levels may negatively affect the outcome of the hypertensive state. PMID- 22089114 TI - Aberrant regulation of the MRP3 gene in non-small cell lung carcinoma. AB - INTRODUCTION: Multidrug-resistant protein-3 (MRP3), a membrane-bound transporter, facilitates efflux of toxic compounds, including certain chemotherapies, out of cells. Aberrant MRP3 expression has been linked to drug resistance in non-small cell lung carcinoma (NSCLC). We sought to determine if tumor MRP3 expression patterns correlate with the mutational status of upstream regulators, including nuclear factor erythroid-2-related factor 2 (Nrf2) and its functional repressor Keap1 in NSCLC cell lines and patient samples. METHODS: To identify putative Nrf2 binding sites in the MRP3 promoter and to evaluate Keap1, Nrf2, and p53 mutation status in four cell lines and 33 NSCLC surgically resected tumor specimens with regard to their impact on MRP3 levels. RESULTS: Chromatin immunoprecipitation analysis of the MRP3 promoter revealed an almost threefold increase in Nrf2 binding to the third putative Nrf2-binding sequence distal to the start site, demonstrating direct regulation of MRP3 by Nrf2. In NSCLC cell lines, elevated Nrf2 protein was observed in cell lines with increased MRP3 RNA expression. In patient tumor specimens, the presence of mutations in Keap1/Nrf2 correlated with MRP3 RNA levels (p < 0.05). p53 mutations were observed in 33% of cases, and all Keap1 mutant-positive tumors possessed a p53 mutation (n = 5; p = 0.0019). CONCLUSIONS: We demonstrate direct involvement between the transcription factor Nrf2 and the MRP3 promoter, which leads to the up-regulation of the MRP3 gene. In addition, we found a statistically significant correlation between the presence of Keap1/Nrf2 mutations and increased MRP3 messenger RNA levels in our NSCLC patient samples. PMID- 22089115 TI - Nicotinamide phosphoribosyltransferase: a potent therapeutic target in non-small cell lung cancer with epidermal growth factor receptor-gene mutation. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) often has an epidermal growth factor receptor (EGFR) gene mutation. Growth of EGFR-gene-mutated NSCLC depends predominantly on EGFR signaling and requires a large amount of intracellular ATP to activate EGFR signal transduction. Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in nicotinamide adenine dinucleotide biosynthesis, and it regulates intracellular ATP levels in mammalian cells. The effect of NAMPT inhibition on NSCLC has not been completely understood. METHODS: We aimed to clarify the hypothesis that NAMPT inhibition suppresses growth of EGFR-gene-mutated NSCLC through reduction of intracellular ATP levels, using NAMPT-siRNA transfection and NAMPT inhibitor FK866. We used four lung adenocarcinoma cell lines, including H358 (Wild type EGFR), LC2 (EGFR), PC9 (EGFR), and H1975 (EGFR), and evaluated the effect of FK866 on these cells and its mechanisms, using cell proliferation, Western blot, ATP, and apoptosis assay. RESULTS: We found that (1) H358, LC2, and H1975 cell lines highly expressed NAMPT mRNA; (2) NAMPT-specific siRNA and FK866 suppressed proliferation of these NSCLCs; (3) FK866 reduced intracellular ATP levels in H1975 cells; (4) FK866 dephosphorylated EGFR signal proteins, including EGFR, Akt, Map kinase kinase 1/2, and extracellular signal-regulated kinase 1/2 (ERK 1/2); (5) FK866 induced apoptosis of H1975 cells; and (6) FK866 suppressed growth of H1975 xenograft tumors and attenuated expression of phospho-ERK 1/2 in the tumors in a tumor bearing mouse model. CONCLUSION: These findings indicate that NAMPT is a potent therapeutic target in the treatment of EGFR-gene-mutated NSCLC. PMID- 22089116 TI - Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. AB - INTRODUCTION: Leptomeningeal metastasis (LM), or leptomeningeal carcinomatosis, is a devastating complication of non-small cell lung cancer (NSCLC), and the optimal therapeutic approach remains challenging. A retrospective review was carried out to assess the impact of whole brain radiotherapy (WBRT), intrathecal therapy (IT), and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) on outcomes. METHODS: Patients with newly diagnosed LM from NSCLC from January 2002 to December 2009 were identified through institutional databases and medical records reviewed. Survival was assessed by Kaplan-Meier and landmark analyses by administered treatment to minimize selection bias. RESULTS: We identified 125 patients (45 men, 80 women) with LM from NSCLC, median age 59 years (range, 28-87 years). Almost all (123 [98%]) patients have died and median overall survival was 3.0 months (95% confidence interval, 2.0-4.0). No differences in survival were seen between patients who were treated with WBRT (n =46) and those who were not (n =59, p =0.84) in a landmark analysis. In the seven patients selected to receive IT chemotherapy, median survival was 18 months (range, 5-33 months) and appeared superior to those not selected for this treatment (p =0.001) in a landmark analysis. The median survival of the nine patients with known EGFR mutations (all of whom received TKIs at some point) was 14 months (range, 1-28 months). CONCLUSIONS: This retrospective study, the largest published series, demonstrates the poor survival of LM from NSCLC. In this study, survival was not improved by WBRT. The survival of patients selected for IT chemotherapy and those with EGFR mutations treated with TKIs highlights the importance of developing novel agents. PMID- 22089117 TI - Hepatocyte growth factor induces resistance to anti-epidermal growth factor receptor antibody in lung cancer. AB - INTRODUCTION: Epidermal growth factor receptor (EGFR) is an attractive drug target in lung cancer, with several anti-EGFR antibodies and small-molecule inhibitors showing efficacy in lung cancer patients. Patients, however, may develop resistance to EGFR inhibitors. We demonstrated previously that hepatocyte growth factor (HGF) induced resistance to EGFR tyrosine kinase inhibitors in lung cancers harboring EGFR mutations. We therefore determined whether HGF could induce resistance to the anti-EGFR antibody (EGFR Ab) cetuximab in lung cancer cells, regardless of EGFR gene status. METHODS: Cetuximab sensitivity and signal transduction in lung cancer cells were examined in the presence or absence of HGF, HGF-producing fibroblasts, and cells tranfected with the HGF gene in vitro and in vivo. RESULTS: HGF induced resistance to cetuximab in H292 (EGFR wild) and Ma-1(EGFR mutant) cells. Western blotting showed that HGF-induced resistance was mediated by the Met/Gab1/Akt signaling pathway. Resistance of H292 and Ma-1 cells to cetuximab was also induced by coculture with lung fibroblasts producing high levels of HGF and by cells stably transfected with the HGF gene. This resistance was abrogated by treatment with anti-HGF neutralizing antibody. CONCLUSIONS: HGF mediated resistance is a novel mechanism of resistance to EGFR Ab in lung cancers, with fibroblast-derived HGF inducing cetuximab resistance in H292 tumors in vivo. The involvement of HGF-Met-mediated signaling should be assessed in acquired resistance to EGFR Ab in lung cancer, regardless of EGFR gene status. PMID- 22089118 TI - Predictors of postoperative quality of life after surgery for lung cancer. AB - INTRODUCTION: The aim was to analyze the association between selected patient variables and health-related quality of life 6 months after surgery for lung cancer. METHODS: In a prospective population-based cohort study, Short Form 36 (SF-36) was used to assess quality of life before and 6 months after surgery for lung cancer. The change in SF-36 summary and subscale scores were used to categorize quality of life in two groups (worse or stable/improved) at 6 months compared with baseline. Logistic regression models adjusting for potential confounding factors were used to analyze the association between patient variables and quality of life 6 months after surgery. RESULTS: A baseline SF-36 questionnaire was completed by 249 patients. Nonresponders at 6 months (n = 36) were excluded, and 14 patients who died before 6 months follow-up remained in the study, leaving 213 patients available for analysis. Gender, comorbidity, occurrence of postoperative complications, and tumor stage were not associated with the physical aspect of quality of life 6 months after surgery. The extent of resection, age, and adjuvant therapy was significantly associated with a clinically relevant decline in the SF-36 physical component summary score 6 months postoperatively. No patient variables were predictive of a decline in the mental component summary score. CONCLUSIONS: The extent of resection, age, and adjuvant therapy was associated with a clinically relevant decline in the physical aspect of health-related quality of life 6 months after surgery. Further studies are needed to explore possible mechanisms. PMID- 22089124 TI - What's new in Shock, December 2011? PMID- 22089125 TI - Direct delivery of low-dose 7-nitroindazole into the bronchial artery attenuates pulmonary pathophysiology after smoke inhalation and burn injury in an ovine model. AB - Bronchial circulation plays a critical role in the pathophysiology of burn and smoke inhalation-induced acute lung injury. A 10-fold increase in bronchial blood flow is associated with excessive production of nitric oxide (NO) following smoke inhalation and cutaneous burn. Because an increased release of neuropeptides from the airway has been implicated in smoke inhalation injury, we hypothesized that direct delivery into the bronchial artery of low-dose 7-nitroindazole (7-NI), a specific neuronal NO synthase inhibitor, would attenuate smoke/burn-induced acute lung injury. Eighteen adult female sheep were instrumented for chronic hemodynamic monitoring 5 to 7 days before the injury. The bronchial artery was cannulated via intercostal thoracotomy, while blood flow was preserved. Acute lung injury was induced by 40% total body surface area third-degree cutaneous burn and smoke inhalation (48 breaths of cotton smoke, <40 degrees C) under deep anesthesia. Following injury, animals (35.4 +/- 1.1 kg) were divided into three groups: (a) 7-NI group: 1 h after injury, 7-NI (0.01 mg . kg . h, 2 mL . h) was continuously infused into the bronchial artery, n = 6; (b) control group: 1 h after injury, same amount of saline was injected into the bronchial artery, n = 6; (c) sham group: no injury, no treatment, same operation and anesthesia, n = 6. After injury, all animals were ventilated and fluid resuscitated according to an established protocol. The experiment was conducted for 24 h. Injury induced severe pulmonary dysfunction, which was associated with increases in lung edema formation, airway obstruction, malondialdehyde, and nitrate/nitrite. 7 Nitroindazole injection into the bronchial artery reduced the degree of lung edema formation and improved pulmonary gas exchange. The increase in malondialdehyde and nitrate/nitrite in lung tissue was attenuated by treatment. Our data strongly suggest that local airway production of NO contributes to pulmonary dysfunction following smoke inhalation and burn injury. Most mechanisms that drive this pathophysiology reside in the airway. PMID- 22089126 TI - Unexpected 100% survival following 60% blood loss using small-volume 7.5% NaCl with adenocaine and Mg(2+) in the rat model of extreme hemorrhagic shock. AB - Hemorrhage is responsible for up to 40% of trauma mortality, and of these deaths, 33% to 56% occur during the prehospital period. In an effort to translate the cardioprotective effects of Adenocaine (adenosine, lidocaine) and Mg (ALM) from cardiac surgery to resuscitation science, we examined the early resuscitative effects of 7.5% NaCl with ALM in the rat model of 60% blood loss. Male Sprague Dawley rats (250-350 g, n = 40) were anesthetized and randomly assigned to one of five groups: (a) untreated, (b) 7.5% NaCl, (c) 7.5% NaCl/6% dextran 70, (d) 7.5% NaCl/Mg, and (e) 7.5% NaCl/ALM. Blood withdrawal occurred over ~50 min (MAP 30-35 mmHg), and rats were left in shock for 30 min. Total shock time was ~80 min; 0.3 mL bolus was injected intravenously over 10 s, and hemodynamics monitored for 60 min (phase 1). Shed blood was reinfused and function monitored for a further 60 min (phase 2). Lead II electrocardiogram, arterial pressures, mean arterial pressure (MAP), pulse pressure (PP), heart rate (HR), and rate-pressure product were monitored. Mortality was as follows: untreated (100%), 7.5% NaCl (75%), 7.5% NaCl/6% dextran 70 (87.5%), 7.5% NaCl/Mg (62.5%), and 7.5% NaCl/ALM (0%). Deaths occurred at different times depending on treatment group and paralleled differences in the total number of ventricular arrhythmias with the highest number in untreated animals (49 +/- 17) and lowest in 7.5% NaCl/ALM rats (2 +/- 1.8) (P < 0.05). At the end of phase 1, MAP of 7.5% NaCl/ALM-treated animals increased from 29 to 40 mmHg (P < 0.05). At the end of phase 2, MAP, PP, HR, and rate-pressure product in the ALM group were 75%, 193%, 96%, and 83% of their preshock values. Small-volume (~1 mL/kg) i.v. bolus of 7.5% NaCl/ALM led to 100% survival following 60% blood loss with higher MAP than any group, an 89% to 96% reduction in the total number of arrhythmias, and a stable HR. PMID- 22089127 TI - In vivo Toll-like receptor 4 antagonism restores cardiac function during endotoxemia. AB - Severe sepsis and septic shock are often accompanied by acute cardiovascular depression. Lipopolysaccharide (LPS) signaling via Toll-like receptor 4 (TLR4) can induce septic organ dysfunction. The aim of this study was to elucidate the in vivo impact of pharmacological TLR4 antagonism on LPS-induced cardiovascular depression using eritoran tetrasodium (E5564). To simulate sepsis, C3H/HeN mice were challenged i.p. with 2 mg/kg body weight LPS. With the intent to antagonize the LPS effects, eritoran was administered i.v. (4 mg/kg body weight). Physical activity, peripheral blood pressure, and heart frequency were recorded before and after LPS and eritoran injection. In addition, intracardiac hemodynamic parameters were analyzed with a pressure conductance catheter. After 2 and 6 h of LPS stimulation +/- eritoran treatment, the hearts and aortae were harvested, and TLR as well as inflammatory mediator expression was measured using reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Lipopolysaccharide significantly decreased arterial blood pressure over time. Administration of eritoran partially prevented the LPS dependent reduction in blood pressure and preserved cardiac function. In addition, LPS increased the expression of CD14 and TLR2 in cardiac and aortic tissue. In aortic tissue, eritoran attenuated this increase, whereas no significant reduction was observed in the heart. Furthermore, cardiac and aortic inducible nitric oxide synthetase mRNA levels were significantly increased 6 h after LPS application. This effect was reduced in the presence of eritoran. In summary, the beneficial influence of eritoran on cardiovascular function in vivo seems to rely mainly on reduction of LPS-induced inducible nitric oxide synthetase expression as well as on attenuated cytokine expression in the vascular wall. PMID- 22089128 TI - Treatment of myocardial dysfunction in sepsis: the Toll-like receptor antagonist approach. PMID- 22089130 TI - Control over the oxidative reactivity of metalloporphyrins. Efficient electrosynthesis of meso,meso-linked zinc porphyrin dimer. AB - The electrochemical oxidation of zinc(II) 5,15-p-ditolyl-10-phenylporphyrin at its first oxidation potential leads to the formation of the corresponding meso meso porphyrin dimer as the main product. The number of electrons abstracted, the addition of the hindered base 2,6-lutidine as well as operating in DMF, instead of a CH(2)Cl(2)/CH(3)CN mixture are the key parameters to obtain high yields of the desired coupling product. Indeed, when the electrolyses are carried out in the CH(2)Cl(2)/CH(3)CN mixture, the unexpected zinc(II) 5-chloro-10,20-p-ditolyl 15-phenyl porphyrin is produced as a by-product, the chlorine atom originating from the CH(2)Cl(2) solvent. The monomer and the dimer are characterised by electrochemical analysis. The signature of the dimer is clearly distinguished on the cyclic voltammogram of the monomer on condition of the prior addition of 2,6 lutidine as a hindered base, indicating that the dimerisation process is thus strongly accelerated. Besides, unprecedented X-ray crystallographic structures of the monomer and the meso-meso dimer are presented and their respective structural parameters are compared. PMID- 22089129 TI - Mutation in the CPC motif-containing 6th transmembrane domain affects intracellular localization, trafficking and copper transport efficiency of ATP7A protein in mosaic mutant mice--an animal model of Menkes disease. AB - Copper is an essential micronutrient for all living organisms. ATP7A protein is a copper-transporting ATPase which plays a vital role in the maintenance of cellular copper homeostasis in mammals. This protein is retained within the trans Golgi network, but after binding copper it can be translocated to the cell membrane to participate in the efflux of excess Cu. Mutation of the ATP7A gene in humans results in the severe neurodegenerative disorder, Menkes disease. The mouse ATP7A homolog encodes a protein that plays the same role in copper transport. Mosaic mutant mice display a lethal phenotype which resembles Menkes disease, although the underlying molecular defect has not been characterized until now. In the present study we identified a G to C nucleotide exchange in exon 15 of the Atp7a gene in mosaic mutants, which resulted in an arginine to proline substitution in the highly conserved 6th transmembrane domain of the ATP7A protein. This mutated protein was mislocalized in kidney cells isolated from mosaic mutant mice, and following exposure of these cells to increased copper concentrations it was not translocated to the plasma membrane. Disturbance of ATP7A function in mosaic mice results in increased copper accumulation in the small intestine and kidneys, and in Cu deficiency in the brain, liver and heart. Mouse models of Menkes disease belong to the mottled mutant group. The mosaic mutant represents another interesting animal model for Menkes disease that will be of value in research on copper metabolism and transport in mammals. PMID- 22089131 TI - Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour. AB - Heritable variation in behavioural traits generally has a complex genetic basis, and thus naturally occurring polymorphisms that influence behaviour have been defined only in rare instances. The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic variation in this species and provided insights into its diverse microbial ecology. C. elegans responds to bacterial infection with conserved innate immune responses and, although lacking the immunological memory of vertebrate adaptive immunity, shows an aversive learning response to pathogenic bacteria. Here, we report the molecular characterization of naturally occurring coding polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1 each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuron specific rescue and ablation experiments and genetic interaction analysis indicate that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-1 (ref. 10), which we have previously shown promotes P. aeruginosa lawn avoidance behaviour. Our data establish a molecular basis for natural variation in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens. PMID- 22089133 TI - The alignment of molecular cloud magnetic fields with the spiral arms in M33. AB - The formation of molecular clouds, which serve as stellar nurseries in galaxies, is poorly understood. A class of cloud formation models suggests that a large scale galactic magnetic field is irrelevant at the scale of individual clouds, because the turbulence and rotation of a cloud may randomize the orientation of its magnetic field. Alternatively, galactic fields could be strong enough to impose their direction upon individual clouds, thereby regulating cloud accumulation and fragmentation, and affecting the rate and efficiency of star formation. Our location in the disk of the Galaxy makes an assessment of the situation difficult. Here we report observations of the magnetic field orientation of six giant molecular cloud complexes in the nearby, almost face-on, galaxy M33. The fields are aligned with the spiral arms, suggesting that the large-scale field in M33 anchors the clouds. PMID- 22089132 TI - The Medicago genome provides insight into the evolution of rhizobial symbioses. AB - Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing ~94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox. PMID- 22089134 TI - Additive threats from pathogens, climate and land-use change for global amphibian diversity. AB - Amphibian population declines far exceed those of other vertebrate groups, with 30% of all species listed as threatened by the International Union for Conservation of Nature. The causes of these declines are a matter of continued research, but probably include climate change, land-use change and spread of the pathogenic fungal disease chytridiomycosis. Here we assess the spatial distribution and interactions of these primary threats in relation to the global distribution of amphibian species. We show that the greatest proportions of species negatively affected by climate change are projected to be found in Africa, parts of northern South America and the Andes. Regions with the highest projected impact of land-use and climate change coincide, but there is little spatial overlap with regions highly threatened by the fungal disease. Overall, the areas harbouring the richest amphibian faunas are disproportionately more affected by one or multiple threat factors than areas with low richness. Amphibian declines are likely to accelerate in the twenty-first century, because multiple drivers of extinction could jeopardize their populations more than previous, mono-causal, assessments have suggested. PMID- 22089135 TI - Active formation of 'chaos terrain' over shallow subsurface water on Europa. AB - Europa, the innermost icy satellite of Jupiter, has a tortured young surface and sustains a liquid water ocean below an ice shell of highly debated thickness. Quasi-circular areas of ice disruption called chaos terrains are unique to Europa, and both their formation and the ice-shell thickness depend on Europa's thermal state. No model so far has been able to explain why features such as Conamara Chaos stand above surrounding terrain and contain matrix domes. Melt through of a thin (few-kilometre) shell is thermodynamically improbable and cannot raise the ice. The buoyancy of material rising as either plumes of warm, pure ice called diapirs or convective cells in a thick (>10 kilometres) shell is insufficient to produce the observed chaos heights, and no single plume can create matrix domes. Here we report an analysis of archival data from Europa, guided by processes observed within Earth's subglacial volcanoes and ice shelves. The data suggest that chaos terrains form above liquid water lenses perched within the ice shell as shallow as 3 kilometres. Our results suggest that ice water interactions and freeze-out give rise to the diverse morphologies and topography of chaos terrains. The sunken topography of Thera Macula indicates that Europa is actively resurfacing over a lens comparable in volume to the Great Lakes in North America. PMID- 22089136 TI - Intermediates in the transformation of phosphonates to phosphate by bacteria. AB - Phosphorus is an essential element for all known forms of life. In living systems, phosphorus is an integral component of nucleic acids, carbohydrates and phospholipids, where it is incorporated as a derivative of phosphate. However, most Gram-negative bacteria have the capability to use phosphonates as a nutritional source of phosphorus under conditions of phosphate starvation. In these organisms, methylphosphonate is converted to phosphate and methane. In a formal sense, this transformation is a hydrolytic cleavage of a carbon-phosphorus (C-P) bond, but a general enzymatic mechanism for the activation and conversion of alkylphosphonates to phosphate and an alkane has not been elucidated despite much effort for more than two decades. The actual mechanism for C-P bond cleavage is likely to be a radical-based transformation. In Escherichia coli, the catalytic machinery for the C-P lyase reaction has been localized to the phn gene cluster. This operon consists of the 14 genes phnC, phnD, ..., phnP. Genetic and biochemical experiments have demonstrated that the genes phnG, phnH, ..., phnM encode proteins that are essential for the conversion of phosphonates to phosphate and that the proteins encoded by the other genes in the operon have auxiliary functions. There are no functional annotations for any of the seven proteins considered essential for C-P bond cleavage. Here we show that methylphosphonate reacts with MgATP to form alpha-D-ribose-1-methylphosphonate-5 triphosphate (RPnTP) and adenine. The triphosphate moiety of RPnTP is hydrolysed to pyrophosphate and alpha-D-ribose-1-methylphosphonate-5-phosphate (PRPn). The C P bond of PRPn is subsequently cleaved in a radical-based reaction producing alpha-D-ribose-1,2-cyclic-phosphate-5-phosphate and methane in the presence of S adenosyl-L-methionine. Substantial quantities of phosphonates are produced worldwide for industrial processes, detergents, herbicides and pharmaceuticals. Our elucidation of the chemical steps for the biodegradation of alkylphosphonates shows how these compounds can be metabolized and recycled to phosphate. PMID- 22089137 TI - Planetary science: Europa awakening. PMID- 22089138 TI - Direct use of dioxygen as an oxygen source: catalytic oxidative synthesis of amides. AB - The first transition-metal-catalyzed direct oxidative synthesis of amides by using dioxygen as an oxygen source has been developed under mild conditions, in which DBU was used as the key additive. The present methodology, which utilizes dioxygen as an oxidant and oxygen source and cheap copper salts as catalysts, opens up an interesting and attractive avenue for the synthesis of amide functionality. PMID- 22089139 TI - Diarrhea associated with Shigella in children and susceptibility to antimicrobials. AB - OBJECTIVE: To evaluate the distribution and susceptibility to antimicrobials of Shigella isolated from children with acute diarrhea and without diarrhea in Teresina, state of Piaui, Brazil. METHODS: Four hundred children aged up to 60 months were studied. Stools were collected from all the patients between January 2004 and August 2007. Shigella was identified by conventional methods and antibiogram and extended-spectrum beta-lactamase (ESBL) were performed by agar diffusion. RESULTS: Shigellosis was only detected in children with acute diarrhea (26/250; 10.4%), especially in those aged from 6 to 24 months and in the rainy months. Shigella was susceptible to ceftriaxone, ciprofloxacin and nalidixic acid. More than half of the strains were resistant to sulphametoxazole trimethoprim and ampicillin. ESBL was not detected. CONCLUSIONS: S. flexneri is common in Teresina. The resistance to ampicillin and sulphametoxazole trimethoprim gives cause for concern, as these drugs are widely used in practice and sulphametoxazole-trimethoprim is also recommended for treating children suspected of having shigellosis. PMID- 22089140 TI - Probing the structure of long DNA molecules in solution using synchrotron radiation linear dichroism. AB - Linear dichroism (LD), a spectroscopic method for aligned samples, has been used with a synchrotron radiation source to reveal insights into the structure and stability of DNA with increasing salt concentrations (thus stabilizing the base pairing) and increasing temperature while remaining below the melting point (thus destabilizing the base pairing). Measurements have been made from 350 nm to 182 nm, and the spectral changes observed quantified using a Bayesian Markov chain Monte Carlo (MCMC) algorithm, which uses statistical methods to fit to experimental data. Based on literature H-D exchange experiments, we surmise that the cause of the spectral variations is the induction of transient single stranding of tracts in the DNA polymer, particularly those with significant content of the weaker AT base pairs. More detailed analysis of the LD data will require better nucleotide transition polarization assignments. PMID- 22089141 TI - HDAC6 and SIRT2 promote bladder cancer cell migration and invasion by targeting cortactin. AB - Histone deacetylase 6 (HDAC6) promotes cell motility and contributes to the metastasis of cancers. The purpose of this study was to investigate the role of HDAC6 in human bladder cancer for the first time. The results showed that HDAC6 promotes the migration and invasion of bladder cancer cells by targeting the cytoskeletal protein cortactin. Furthermore, a colony formation assay as well as in vitro migration and invasion assays demonstrated that this migration and invasion was suppressed by the HDAC6-specific inhibitor tubacin. In addition, cortactin is the substrate of SIRT2, which also belongs to the family of histone deacetylases. We demonstrated that by using SIRT2-specific siRNA combined with tubacin treatment, the cell migratory and invasive abilities were dramatically suppressed. Taken together, we conclude that HDAC6 and SIRT2 work synergistically to promote cell migration and invasion in bladder cancer, and the HDAC6-specific inhibitor tubacin may be regarded as a novel therapeutic agent for bladder cancer. PMID- 22089142 TI - Socially excluded individuals fail to recruit medial prefrontal cortex for negative social scenes. AB - Converging behavioral evidence suggests that people respond to experiences of social exclusion with both defensive and affiliative strategies, allowing them to avoid further distress while also encouraging re-establishment of positive social connections. However, there are unresolved questions regarding the cognitive mechanisms underlying people's responses to social exclusion. Here, we sought to gain insight into these behavioral tendencies by using functional magnetic resonance imaging (fMRI) to examine the impact of social exclusion on neural responses to visual scenes that varied on dimensions of sociality and emotional valence. Compared to socially included participants, socially excluded participants failed to recruit dorsomedial prefrontal cortex (dmPFC), a brain region involved in mentalizing, for negative social scenes. Moreover, following social exclusion, dmPFC demonstrated a linear effect of valence, with greater activity to positive social scenes compared to negative social scenes. These results suggest that, following social exclusion, people display a preference for mentalizing about positive social information and tend to avoid negative aspects of their social world. PMID- 22089143 TI - Use of troponin as a screen for chest pain in the pediatric emergency department. AB - Troponin levels are commonly employed in the assessment of adults presenting with chest pain or concern for coronary ischemia. However, the utility of troponin measurements in children is not well defined. The purpose of this study was to review the use and clinical yield of serum troponin assay in a large pediatric emergency department (ED). We identified all patients <22 years of age, not previously known to have cardiac disease, who presented with chest pain and whose troponin levels were evaluated in our pediatric ED during a 7-year period. Test results were correlated to patient factors, such as chief complaint, cardiac history, diagnostic workup, and discharge diagnoses. Of the 212 study patients who presented with chest pain, troponin levels were increased (>= 0.1 ng/ml) in 37 (17%) subjects. The disposition for these 37 subjects included transfer to adult facility (n = 6), admission to our pediatric inpatient service (n = 27), and discharge to home from the ED (n = 10). Only one subject had an acute myocardial infarction. For those with increased troponin level, 18 of 37 (48%) cases were attributed to a primary cardiac diagnosis with the most common discharge diagnosis of myocarditis or pericarditis. In the pediatric ED setting, selective use of troponin assay may be a useful test in the management of patients with chest pain. Most cases of increased troponin level related to chest pain represent myocarditis, often mild and self-resolving. Given the low likelihood that acute coronary syndrome is the etiology of chest pain, immediate transfer to an adult facility for the majority of patients with increase of troponin does not appear warranted. PMID- 22089144 TI - [Cerebral amyloid angiopathy with associated vasculitis]. PMID- 22089145 TI - Implementation of assertive community treatment in Australia: model fidelity, patient characteristics and staff experiences. AB - The impact of variable implementation of the Assertive Community Treatment (ACT) model on patient outcomes is increasingly recognised. We conducted the first study of four established Australian ACT teams, examining team composition, processes and model fidelity, using previously validated questionnaires. Demographic and clinical details of patients and their own experiences of ACT were gathered from staff. Associations between burnout and work experiences were examined. All teams were ACT-like (mean DACTS score = 3.7, SD = 0.3) with few significant patient differences between teams, except diagnosis (schizophrenia 61 93%, co-morbid substance abuse 16-33%) and proportion living alone (23-72%). Clinicians were fairly satisfied, but inter-team differences in staffing profile and experience emerged and one team scored highly on emotional exhaustion. Increased burnout was associated with greater stress due to taking a team approach. Inter-team differences suggested that attention to effective team working and leadership, as well as model fidelity, may be warranted. PMID- 22089146 TI - The pathway of internalizing and externalizing problems from childhood to adolescence: a prospective study from age 7 to 14-16 in Korea. AB - This study prospectively investigated developmental psychopathology pathway from the age of 7 to ages 14-16. The subjects (N = 1,857) were evaluated using the Korean version of the Child Behavior Checklist and reassessed using the Korean Youth Self Report. In path analyses, total problems, externalizing problems, and internalizing problems in childhood associated significantly with problems in adolescence. In particular, childhood externalizing problems associated with adolescent externalizing problems, for both genders. However, our results differ from those of previous studies in that internalizing problems showed a restrictive stability by gender and in that early externalizing problems correlated negatively with later internalizing problems for girls. In the syndrome scales analyses, we confirmed that some syndromes showed heterotypic pathways, despite the general continuity of the developmental psychopathology. The importance of Anxiety/Depression and Attention problems in childhood suggested that adolescent difficulties are a consequence of an accumulation of such risk factors. PMID- 22089147 TI - Spontaneous retinal venous pulsatility in patients with cyanotic congenital heart disease. AB - Spontaneous retinal venous pulsations (SRVP) are assessed as a clinical marker for patients with ophthalmic or neurological disorders. The pulsations are influenced by intraocular pressure (IOP), cerebrospinal fluid pressure (CSFp), and retinal venous pressure (RVP). However, little is known about the effect of cyanosis with polycythemia, a common finding in adults with complex congenital heart disease (CHD), on SRVP. This study investigated 11 subjects with long standing cyanosis secondary to CHD and 11 control subjects to determine if there were measurable differences in resting pulsatility for a given IOP level. Intraocular pressure was measured using Goldman tonometry, and dynamic SRVP was recorded noninvasively using a retinal vessel imaging system. Peak amplitude of SRVP at each cardiac cycle was measured and compared with IOP. Heart rate was also monitored during the tests. Results show that for a similar baseline IOP, SRVP amplitudes are significantly lower in cyanotic patients compared with normal subjects (P < 0.0001). This may be explained by an increased RVP or high CSFp in these patients. Mean venous diameter is also significantly higher in cyanotic patients (P < 0.01), but no significant relationship was found between SRVP or diameter with blood parameters. PMID- 22089148 TI - How the concentration of insulin affects the development of preantral follicles in goats. AB - This study investigated the effect of adding different insulin concentrations to the culture medium for goat preantral follicle development in vitro. The ovarian fragments were immediately fixed or cultured for 7 days in MEM with insulin (0, 5, 10 ng/ml and 5 or 10 MUg/ml). The results showed that, after 7 days of culture, insulin at 10 ng/ml was the best concentration to preserve follicular viability and ultrastructure, resulting in the highest rates of normal follicles. After 7 days, only treatments with 10 ng/ml and 5 MUg/ml of insulin increased follicular activation when compared to other concentrations. Regarding follicular and oocyte growth, the presence of 10 ng/ml of insulin promoted a larger diameter than other treatments. In conclusion, this study shows that addition of 10 ng/ml of insulin to the culture medium improved the survival and stimulated growth of goat preantral follicles. PMID- 22089149 TI - [Incidence and risk factors of early postoperative paralytic ileus after radical cystectomy and cutaneous ureterostomy with a unilateral and parallel stoma]. AB - To identify the incidence and risk factors for developing early postoperative paralytic ileus (POPI) after radical cystectomy and cutaneous ureterostomy with a unilateral and parallel stoma, we retrospectively reviewed 21 patients (mean age 73.0, 19 males and 2 females) with a minimum of 3 months of follow-up. POPI occurred in 4 patients (19.0%), who did not need surgical treatment and the insertion of a nasogastric tube. Age and past history of abdominal surgery influenced the occurrence of POPI. The patients with and without POPI had a mean age of 82.3+/-7.4 and 70.8+/-6.3 years old, respectively (p=0.0025), and 75.0% (3/4) and 11.8% (2/17) of the patients, respectively, had a past history of abdominal surgery (p= 0.0276). There were no significant differences between patients with and without POPI in any of the following factors examined : sex, body mass index, American Society of Anesthesiologists score, pT-category, neoadjuvant chemotherapy, preoperative serum levels of hemoglobin, creatinine, total protein, and albumin, operative time, blood loss, transfusion volume, stomal side, postoperative day of ambulation, and removal of epidural anesthesia tube. In conclusion, our results showed that increasing age and a past history of abdominal surgery were significantly associated with the occurrence of POPI after radical cystectomy and cutaneous ureterostomy. PMID- 22089150 TI - [The state of antimicrobial prophylaxis for holmium laser enucleation of the prostate : HoLEP and the results of a questionnaire survey]. AB - Holmium laser enucleation of the prostate (HoLEP) has been established as a procedure for the treatment of patients with benign prostate hyperplasia, instead of transurethral resection of prostate (TURP). To determine the appropriate antimicrobial prophylaxis for the prevention of perioperative urinary tract infection following HoLEP we sent a questionnaire to 79 institutes belonging to the Japanese Urological Association. We surveyed 1) the performance of HoLEP, 2) number of HoLEP performed in 2009, 3) antimicrobial agents and the term of the administration for prophylaxis, 4) rate of perioperative infections, and 5) usage of other antimicrobial prophylaxis in HoLEP, as compared with in TUR-P. We received answers from 59 institutes (74. 9%). We examined 43 responses, which were obtained from executive members who performed more than eleven cases of HoLEP in 2009. Thirty-one of these institutes (72.1%) indicated parenteral antibiotics ; three of them adopted oral antibiotics, and nine of them added oral antibiotics following parenteral antibiotics. In 40 of them (93.0%), the rate of perioperative infections was reported to be fewer than 5%. Twenty-seven of them (62. 7%) adopted the same schedule for the prophylaxis in both HoLEP and TUR-P. Eleven of them indicated shorter antimicrobial usage in HoLEP than in TUR-P. Ten of the eleven institutes reported that the rate of perioperative infections in HoLEP had been lower than in TUR-P. Our questionnaire survey demonstrated that shorter antimicrobial prophylaxis might be possible in HoLEP than in TUR-P. PMID- 22089151 TI - [Usefulness of MRI prior to prostate needle biopsy in PSA gray zone]. AB - To evaluate the diagnostic accuracy of prostate magnetic resonance imaging (MRI), we compared MRI findings with the results of biopsy as well as findings from specimens following total prostatectomy. The subjects consisted of 260 males who showed a prostate specific antigen (PSA) level in the gray zone (4 ng/ml <=PSA <10 ng/ml) and also underwent digital rectal examination (DRE), transrectal ultrasound (TRUS), and MRI prior to prostate biopsy between April 2005 and December 2009. In Evaluation 1, the results of DRE/TRUS/MRI were compared with those of prostate biopsy. The biopsy-positive rate was higher in males positive in each examination. However, 24.8% of males negative in all examinations were biopsypositive. Thus, these examinations were considered to be inappropriate for secondary screening. In evaluation 2, the prostate was divided into 4 regions, and the findings from specimens following total prostatectomy were compared with MRI findings in each region. For the region containing prostate cancer, MRI showed a sensitivity of 26.0%, specificity of 98.3%, positive predictive value of 96.2%, and negative predictive value of 44. 4%. In patients with a Gleason score >=7, cancer foci were more frequently detectable using MRI. MRI prior to prostate biopsy in patients in the PSA gray zone is inappropriate for secondary screening due to its low sensitivity. However, by virtue of its high positive predictive value, MRI is useful for determining patients indicated for biopsy, as well as DRE and TRUS. Accurate evaluation of the localization of all cancer lesions is difficult using MRI. However, when MRI findings are present, they frequently indicate the cancer lesion, which may be useful information for treatment. PMID- 22089152 TI - [A case of bilateral renal calculi in a 1-year-old female with adenine phosphoribosyl transferase partial deficiency]. AB - We report a case of bilateral renal calculi in a 1-year-old female with adenine phosphoribosyl transferase (APRT) partial deficiency. She initially visited another institution with high fever as the major complaint. Computed tomography revealed a bilateral renal stone and left hydro nephrosis. In the urine, there were 2, 8-dihydroxyadenine (DHA) crystals. An analysis of the APRT gene revealed the APRT deficiency and the genotype to be APRT*J/APRT*Q0. We performed extracorporeal shock wave lithotripsy (ESWL) under general anesthesia, and as dissolution therapy we administered Meylon through the nephrostomy and citric acid orally. The stone disappeared from her kidney. The analysis of the stone fragments revealed 2,8- dihydroxyadenine (DHA) urolithiasis. PMID- 22089153 TI - [Myocardial metastasis from renal cell carcinoma treated with sorafenib]. AB - We present a case of myocardial metastasis from renal cell carcinoma (RCC) during the treatment with sorafenib. A 63-year-old male, who had undergone right radical nephrectomy, received interferon-alpha (IFN), interleukin (IL-2) and 5 flurouracil (5-FU) for the treatment of lung and pleural metastases. However, since this metastasis showed progressive disease, we administered sorafenib. Nine months after the introduction of sorafenib, he complained of dyspnea. Chest computed tomography and cardiac ultrasonography revealed a low density mass at the cardiac muscle of the left cardiac ventricle, suggesting myocardial metastasis of RCC. Molecular targeted therapy achieved a longer survival in advanced RCC patients in comparison with the immunotherapy using cytokines. Therefore, in metastasis evaluation, some organs which have been regarded as rare sites should be carefully evaluated. PMID- 22089154 TI - [Metachronous urothelial cancer in bilateral upper urinary tracts and bladder associated with hereditary nonpolyposis colorectal cancer]. AB - A 40-year-old man had undergone right hemicolectomy and sigmoidectomy under the diagnosis of ascending and sigmoid colon cancer and right nephroureterectomy under the diagnosis of right ureteral cancer, in 1997 and in 2002, respectively. In 2007, He visited our hospital with a complaint of bloody stool and hematuria. Colon fiberscopy, ureteropelvicscopy and cystoscopy demonstrated colon cancer, left renal pelvis cancer and bladder cancer, respectively, as diagnosed by biopsies, followed by restative colectomy, left nephroureterectomy and cystectomy. The final histopathological examination showed well differentiated adenocarcinoma (pSM) in the colon, and urothelial carcinoma in the left renal pelvis (pT2) and the bladder (pT1). Since his uncle and elder brother had suffered from stomach cancer and colon cancer, respectively, he was diagnosed with hereditary nonpolyposis colorectal cancer (HNPCC : Lynch syndrome). He has been well doing without recurrence for 3 years after the surgery. PMID- 22089155 TI - [A case report of retrocaval ureter associated with right ureteral tumors]. AB - A case of retrocaval ureter associated with right ureteral tumor in a 70-year-old male is reported. The diagnosis was confirmed by CT and RP. Retroperitoneoscopic nephroureterectomy was performed. The histology of the tumor was urethelial carcinoma. After 20 months, there was neither evidence of recurrence nor metastasis. To our knowledge, this is the 11th case of retrocaval ureter associated with upper urinary tract tumors. PMID- 22089156 TI - [Laparoscopic nephrectomy for patients with infected nonfunctioning kidney due to ureteropelvic junction stenosis : report of two cases]. AB - We report two cases of infected nonfunctioning kidney due to ureteropelvic junction (UPJ) stenosis treated by laparoscopic surgery. Patient 1 : A 78-year old woman was referred to our clinic complaining of left flank pain and high fever up. Asymptomatic UPJ stenosis with mild hydronephrosis was diagnosed 9 years ago at our clinic. Therefore we followed her up with no treatment. Computed tomography (CT) scan revealed left severe hydronephrosis. Antibiotic chemotherapy was performed without percutaneous nephrostomy. Laparoscopic nephrectomy was performed with the resected renal size of 10 cm in greatest diameter and the operative time of 262 min. The pathological diagnosis was atrophic kidney with pyelonephritis. Patient 2 : A 28-year-old man was referred to our clinic complaining of left flank pain and high fever up. CT scan revealed a left severe hydronephrosis due to UPJ stenosis. Following percutaneous nephrostomy,antibiotic chemotherapy was performed. Laparoscopic nephrectomy was performed with the resected renal size of 6 cm in greatest diameter and the operative time of 140 min. The pathological diagnosis was atrophic kidney with pyelonephritis. Laparoscopic nephrectomy for infected nonfunctioning kidney due to UPJ stenosis is feasible and safe. With dense perinephric adhesions and failure to progress,we should consider early open conversion to reduce morbidity. PMID- 22089157 TI - [A case of proliferative cystitis forming ureterovesical junction obstruction]. AB - We report a case of proliferative cystitis forming ureterovesical junction obstruction. A 28-year-old man presented with a complaint of gross hematuria. Abdominal ultrasonography revealed left hydronephrosis and bladder tumor. Drip infusion pyelography (DIP) demonstrated left ureterovesical junction obstruction and cystoscopic findings appeared papillary sessile tumor around the bladder neck, trigone, and bilateral ureteral orifice. Transurethral resection of the bladder tumor (TURBT) was performed. The pathological diagnosis of the tumor was proliferative cystitis and confirmed that left ureterovesical junction obstruction was derived from proliferative cystitis. The tumor was not responsive to medical treatment. After the 4th TURBT, the tumor was completely resected, and left hydronephrosis and ureterovesical junction obstruction were improved. One year after the last operation, there is no evidence of recurrence of the tumor. Tumor formation arising from proliferative cystitis is relatively rare. Pathogenesis and management of this rare condition are discussed. PMID- 22089158 TI - [Local recurrence of micropapillary bladder tumor after radical cystectomy : successful treatment with radiation therapy : a case report]. AB - A 75-year-old man consulted a physician because of gross hematuria and right flank pain. Since a bladder tumor and right hydronephrosis were found, the patient was referred to our hospital. The clinical diagnosis was cT3bN0M0 and radical cystectomy was done. The pathological diagnosis was micropapillary variant of urothelial carcinoma, pT3bN0M0. The local recurrence appeared in the interior of the pelvis by computed tomography after the operation. A complete response was obtained by radiotherapy. PMID- 22089159 TI - [Invasive bladder cancer with concomitant carcinoma in situ treated with chemoradiotherapy followed by BCG intravesical infusion therapy to preserve the bladder : report of three cases]. AB - Three patients with invasive bladder cancer and concomitant carcinoma in situ were treated sequentially with chemoradiotherapy followed by BCG intravesical infusion therapy to preserve the bladder. Local complete response was achieved in all patients, although lymph node metastasis was noted in one patient. The multimodality therapy could be safely administered without acute or late complications, including decreased bladder capacity. PMID- 22089160 TI - [Prostate cancer in a young adult : a case report]. AB - We report a case of prostate cancer in a 41-year-old male. The patient initially visited another institution with a chief complaint of left breech pain. He was referred to our hospital for further investigation. Serum level of PSA was 267ng/ml and multiple bone metastases were found on bone scintigram. Digital rectal examination revealed a stony-hard prostate. Computed tomography showed multiple lung and lymph node metastases. Transperineal needle biopsy of the prostate revealed moderately differentiated adenocarcinoma (Gleason score 4+5) frombilateral lobes (the 3th Edition). The patient was diagnosed with cT4N1M1c prostate cancer and maximal androgen blockade therapy was commenced. PMID- 22089161 TI - Antinucleosome in systemic lupus erythematosus. A study in a Brazilian population. AB - Antinucleosome antibodies have been found with variable prevalence in systemic lupus erythematosus (SLE) and were associated with more severe disease. This research aims to study the prevalence of antinucleosome antibodies in a sample of Brazilian adult SLE patients and their association with clinical findings and disease activity. Ninety-two adult patients (81 females and 11 males, with mean age of 37.29 +/- 10.98 years) with SLE were studied for clinical and antibody profile, disease activity by SLE disease activity index (SLEDAI), and presence of antinucleosome antibodies by ELISA. The prevalence of antinucleosome antibodies was 61.9% (mean titer, 87.8 +/- 62.6 U). No relationship was found of antinucleosome presence and any of the studied clinical features. A positive association was detected with anti-DNA (p = 0.001) and SLEDAI (p < 0.0001), but not with anti-Sm, anti-Ro, anti-La, and anti-RNP. No specific disease feature could be associated with the presence of antinucleosome; however, a positive relationship was detected with disease activity measured by SLEDAI and with anti DNA presence. PMID- 22089163 TI - Conclusions and recommendations of the International Expert Symposium in Fukushima: Radiation and Health Risks. PMID- 22089162 TI - Psychosocial problems among newly diagnosed rheumatoid arthritis patients. AB - We identified patients with newly diagnosed rheumatoid arthritis (RA) in the ages 18-65 years who needed psychosocial interventions. A total of 123 patients (90 women) were asked to participate, but 19 declined and 4 dropped out early in the study, leaving a total of 100 patients (75 women) in the sample. Questionnaires used were the Epidemiological Investigation on Rheumatoid Arthritis study questionnaire, the Hospital Anxiety and Depression Scale, the Sense of Coherence (SOC) scale, and the General Coping Questionnaire. Interviews showed that 46% of the included 100 patients had psychosocial problems (PSP). One third of them had problems directly related to RA. The rest had problems with their life situation in general, without or reinforced by RA. Compared to patients without psychosocial problems, PSP patients lived in more strained social situations, especially regarding personal finances and social support. More of the PSP patients were anxious, showed lower SOC scores, and also used more emotion-based coping strategies (resignation, protest, isolation and intrusion) and less problem-oriented (minimization). They also had higher scores on depression and more frequently expected that RA would negatively affect their future. PSP patients also experienced a more negative impact of the disease, a finding not confirmed by the sickness activity score judged by the rheumatologist. Thus, early in the course of RA, screening instruments should be used to identify PSP patients. Psychosocial treatment and support by medical social workers skilled in RA care should be offered. PMID- 22089164 TI - Is occupational therapy practice for older adults with lower limb amputations evidence-based? A systematic review. AB - BACKGROUND: Although occupational therapists are integral to the rehabilitation process of people with amputations, the effectiveness of the occupational therapy intervention for older adults with lower limb amputations has not been investigated. OBJECTIVES: To identify the effectiveness of the occupational therapy interventions with older adults aged 65 years and older with lower limb amputations. STUDY DESIGN: Systematic review. METHODS: A systematic search was conducted in CINAHL, PUBMED, OTSEEKER and OTDBASE from January 1985 to January 2011. The eligible papers were critiqued using a typology, which involved designation of levels of evidence and quality markers. RESULTS: The databases yielded 2,664 potential publications. Of these, only two were included in the final review. These studies suggested that the frequency of the occupational therapy sessions was found to be statistically significantly related to prosthesis use and that service users perceived positive benefits about the provision of stump boards. Both studies had limitations resulting in a need for further investigation in these areas. CONCLUSION: Research evidence on the occupational therapy interventions with this population is limited and scarce. Occupational therapists need to take urgent action to address the identified evidence-based gaps in order to devise informed targeted rehabilitation programmes for this client group. PMID- 22089165 TI - Inhibition of caspase mediated apoptosis restores muscle function after crush injury in rat skeletal muscle. AB - Although muscle regeneration after injury is accompanied by apoptotic cell death, prolonged apoptosis inhibits muscle restoration. The goal of our study was to provide evidence that inhibition of apoptosis improves muscle function following blunt skeletal muscle injury. Therefore, 24 rats were used for induction of injury to the left soleus muscle using an instrumented clamp. All animals received either 3.3 mg/kg i.p. of the pan-caspase inhibitor Z-valinyl-alanyl-DL: aspartyl-fluoromethylketone (z-VAD.fmk) (n = 12 animals) or equivalent volumes of the vehicle solution DMSO (n = 12 animals) at 0 and 48 h after trauma. After assessment of the fast twitch and tetanic contraction capacity of the muscle at days 4 and 14 post injury, sampling of muscle tissue served for analysis of cell apoptosis (cleaved caspase 3 immunohistochemistry), cell proliferation (BrdU immunohistochemistry) as well as of muscle tissue area and myofiber diameter (HE planimetric analysis). Muscle strength analysis after 14 days in the z-VAD.fmk treated group revealed a significant increase in relative muscle strength when compared to the DMSO treated group. In contrast to the DMSO treated injured muscle, showing a transient switch towards a fast-twitching muscle phenotype (significant increase of the twitch-to-tetanic force ratio), z-VAD.fmk treated animals showed an enhanced healing process with a faster restoration of the twitch-to-tetanic force ratio towards the physiological slow-twitching muscle phenotype. This enhancement of muscle function was accompanied by a significant decrease of cell apoptosis and cell proliferation at day 4 as well as by a significant increase of muscle tissue area at day 4. At day 14 after injury z VAD.fmk treated animals presented with a significant increase of myofiber diameter compared to the DMSO treated animals. Thus, z-VAD.fmk could provide a promising option in the anti-apoptotic therapy of muscle injury. PMID- 22089166 TI - Service and wider societal costs of very young children with autism in the UK. AB - Autism spectrum disorders (ASD) are associated with a substantial economic burden, but there is little evidence of the costs in the early years; the period in which children are increasingly likely to be diagnosed. We describe the services used by 152 children aged 24-60 months with autism, report family out-of pocket expenses and productivity losses, and explore the relationship between family characteristics and costs. Children received a wide range of hospital and community services including relatively high levels of contact with speech and language therapists and paediatricians. Total service costs varied greatly (mean L430 per month; range L53 to L1,116), with some families receiving little statutory support. Higher costs were associated with increasing age and symptom severity. PMID- 22089167 TI - Diagnostic yield of chromosomal microarray analysis in an autism primary care practice: which guidelines to implement? AB - Genetic testing is recommended for patients with ASD; however specific recommendations vary by specialty. American Academy of Pediatrics and American Academy of Neurology guidelines recommend G-banded karyotype and Fragile X DNA. The American College of Medical Genetics recommends Chromosomal Microarray Analysis (CMA). We determined the yield of CMA (N = 85), karyotype (N = 119), and fragile X (N = 174) testing in a primary pediatrics autism practice. We found twenty (24%) patients with abnormal CMA results (eight were clinically significant), three abnormal karyotypes and one Fragile X syndrome. There was no relationship between CMA result and cognitive level, seizures, dysmorphology, congenital malformations or behavior. We conclude that CMA should be the clinical standard in all specialties for first tier genetic testing in ASD. PMID- 22089168 TI - TNF-induced necroptosis in L929 cells is tightly regulated by multiple TNFR1 complex I and II members. AB - TNF receptor 1 signaling induces NF-kappaB activation and necroptosis in L929 cells. We previously reported that cellular inhibitor of apoptosis protein mediated receptor-interacting protein 1 (RIP1) ubiquitination acts as a cytoprotective mechanism, whereas knockdown of cylindromatosis, a RIP1 deubiquitinating enzyme, protects against tumor necrosis factor (TNF)-induced necroptosis. We report here that RIP1 is a crucial mediator of canonical NF kappaB activation in L929 cells, therefore questioning the relative cytoprotective contribution of RIP1 ubiquitination versus canonical NF-kappaB activation. We found that attenuated NF-kappaB activation has no impact on TNF induced necroptosis. However, we identified A20 and linear ubiquitin chain assembly complex as negative regulators of necroptosis. Unexpectedly, and in contrast to RIP3, we also found that knockdown of RIP1 did not block TNF cytotoxicity. Cell death typing revealed that RIP1-depleted cells switch from necroptotic to apoptotic death, indicating that RIP1 can also suppress apoptosis in L929 cells. Inversely, we observed that Fas-associated protein via a death domain, cellular FLICE inhibitory protein and caspase-8, which are all involved in the initiation of apoptosis, counteract necroptosis induction. Finally, we also report RIP1-independent but RIP3-mediated necroptosis in the context of TNF signaling in particular conditions. PMID- 22089169 TI - Macrocylic bisbibenzyl natural products and their chemical synthesis. AB - Covering: 1995 to June 2011. The macrocyclic bisbibenzyl family of natural products are commonly found in liverworts and other bryophytes, though the recent isolation of riccardin C from a primrose extract has demonstrated their existence in higher flowering plants. Each has a core comprising four aromatic rings and two ethano bridges, being derived in Nature from two molecules of lunularin. Sub classes are distinguished by the connectivity between these lunularin units, while individual natural products are distinguished by the hydroxy- and/or alkoxy substituents decorating the core structures. Further diversification results from halogenation and oxidation, which may lead to dimerization or the creation of additional rings. The review provides a timely update to a previous Natural Product Reports article by Keseru and Nogradi (Nat. Prod. Rep. 1995, 12, 69-75) and largely focuses on new additions to the family and the strategies used to effect their chemical synthesis. PMID- 22089170 TI - 'Zero' fluoroscopic exposure for ventricular tachycardia ablation in a patient with situs viscerum inversus totalis. AB - Situs viscerum inversus totalis (SVIT) is a congenital disorder characterized by mirror reversal of the thoracic and abdominal organs. Different studies have shown that the ablation procedure can be performed without fluoroscopy with safety and effectiveness, in the setting of supraventricular tachycardia. We successfully performed an anatomical map and a radiofrequency catheter ablation of ventricular arrhythmia in a patient with SVIT without fluoroscopy. PMID- 22089171 TI - Comparison of mucin levels at the ocular surface of postmenopausal women with and without a history of dry eye. AB - PURPOSE: To determine if levels of the glycocalyx membrane mucins, MUC1 and MUC16, and the secreted goblet cell mucin MUC5AC are altered in conjunctival cells and tears of postmenopausal women presenting with a history of non-Sjogren dry eye and if mucin levels correlate with dry eye clinical diagnostic data. METHODS: Eighty-four postmenopausal women with a history of non-Sjogren dry eye and 30 normal subjects were recruited for this study. Impression cytology samples were collected for mucin messenger RNA (mRNA) and protein analysis. Tears were collected for mucin protein assay. Quantitative polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay were used to quantitate MUC1, MUC16, and MUC5AC levels. RESULTS: Postmenopausal women with a history of dry eye displayed significantly increased MUC1 mRNA expression and cellular protein compared with normal subjects (P < 0.001 and P < 0.01, respectively). Similarly, cellular MUC16 protein levels were significantly higher (P < 0.001). Mucin levels were found to be correlated with the clinical characterization of the subjects, including staining and symptoms. Although cellular MUC5AC protein levels were increased in symptomatic subjects, the increase did not reach statistical significance. CONCLUSIONS: Elevation in MUC1 and MUC16 mRNA and/or protein levels in postmenopausal women with non-Sjogren dry eye with a history of dry eye may be a compensatory response to irritation and inflammation associated with the disease. Understanding the pattern of mucin expression associated with the dry eye pathology may clarify factors involved in the progression of the disease and enhance the development of targeted therapies. PMID- 22089172 TI - Persistent lamellar interface fluid with clear cornea after Descemet stripping automated endothelial keratoplasty. AB - PURPOSE: To describe clinical properties of a patient with persistent interface fluid syndrome and clear graft, 3.5 years after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Case report. RESULTS: A 69-year-old woman who had DSAEK in 2006 presented with a clear cornea (no corneal edema) and deep diffuse reticular haze in the right eye. Visual acuity was 20/40. Ultrahigh resolution optical coherence tomography (UHR-OCT) imaging of the right eye demonstrated persistent interface fluid at the donor-recipient junction. The detachment between donor and recipient corneas was 70 MUm at the center. There was no connection between the anterior chamber and the donor/recipient interface. CONCLUSIONS: Despite the persistent detachment of the donor cornea, the recipient cornea can remain clear in persistent interface fluid syndrome after DSAEK. PMID- 22089173 TI - Studying the interactions of a platinum(II) 9-aminoacridine complex with proteins and oligonucleotides by ESI-TOF MS. AB - The interaction of a novel Pt complex, [Pt(dmba)(N9-9AA)(PPh(3))](+)1 (dmba = N,N dimethylbenzylamine-kappaN,kappaC; 9AA = 9-aminoacridine), which exhibits anti tumor activity, with certain key proteins has been monitored by ESI-MS. Also, the interaction of 1 with a designed double-stranded oligonucleotide containing the GG motif has been followed by mass spectrometry as well as by fluorimetry. The results obtained show the low interaction of 1 with the considered proteins and the absence of covalent interaction with the oligonucleotides, but the fluorimetric data confirm the pi-pi interaction of 1 with the double-stranded DNA, which is probably the reason of the previously reported activity of 1 in several tumor cell lines. PMID- 22089174 TI - Reversible phase transformation in proton conducting Strandberg-type POM based metal organic material. AB - A Cu(II)-phenanthroline connected Strandberg-type polyoxometalate based proton conducting MOF, Cu(3)Mo(5)P(2), that contains one dimensional parallel water channels has been reported. Cu(3)Mo(5)P(2) shows proton conduction at room temperature as well as elevated temperature. PMID- 22089175 TI - A single test of antimullerian hormone in late reproductive-aged women is a good predictor of menopause. PMID- 22089177 TI - A randomized double-blind placebo-controlled trial of a Chinese herbal medicine preparation (Jiawei Qing'e Fang) for hot flashes and quality of life in perimenopausal women. AB - OBJECTIVE: This study aimed to evaluate the effectiveness and safety of a Chinese herbal medicine preparation, Jiawei Qing'e Fang (JQF), on menopausal symptoms in perimenopausal women. METHODS: A randomized double-blind placebo-controlled trial was performed over 12 weeks in 72 perimenopausal women who reported 14 or more hot flashes per week. The participants were randomly allocated to receive JQF or placebo for 8 weeks. Posttreatment follow-up was performed 4 weeks after intervention. The primary outcome was the Menopause-Specific Quality of Life. Secondary outcomes included hot flash and plasma lipids. RESULTS: There was greater improvement in hot flash score in the JQF group compared with the placebo group, and the difference between the two groups was statistically significant (P = 0.048). There were between-group differences in vasomotor (P = 0.011) and physical (P = 0.034) domains. The triglyceride (TG) level in the JQF group showed a significant reduction (P = 0.036) in women with a baseline TG greater than 150 mg/dL (1.7 mmol/L). CONCLUSIONS: The Chinese herbal medicine preparation JQF was found to be superior to placebo in reducing hot flashes and improving menopausal symptoms in the vasomotor and physical aspects and might have a potential benefit in reducing TG levels. The herbal medicine preparation was well tolerated, with no serious adverse events noted during the study period. PMID- 22089178 TI - Interaction between oral estrogen plus progestogen therapy and ABO blood groups on coagulation activation in postmenopausal women. AB - OBJECTIVE: The aim of this study was to investigate the effect of postmenopausal hormone therapy on coagulation and whether this effect differs according to ABO blood groups. METHODS: This was a prospective observational study to evaluate factor VIII (FVIII) activity, factor von Willebrand (vWF), and D-dimer (D-Di) levels and ABO blood groups in 61 postmenopausal women using oral estrogen plus progestogen therapy (EPT; 2 mg estradiol + 1 mg norethisterone acetate) for 3 months and in 101 women not using EPT. After 3 months, all eligible women who had completed the treatment scheme proposed for the EPT group or those who opted to participate but had not undergone EPT had a blood sample collected for analysis. RESULTS: Significant differences were observed in FVIII activity and vWF levels in the control group between those carrying group O and non-group O blood. For EPT users, significant differences were observed for FVIII activity, vWF, and D Di levels. After a multivariate regression analysis, FVIII activity and ABO blood groups were independently associated with vWF levels, whereas interaction between ABO blood groups and EPT were independently associated with FVIII activity. Besides diabetes, the ABO * EPT interaction was also noted to be independently associated with D-Di levels. CONCLUSIONS: These findings suggest an interactive effect between oral EPT and non-O blood groups, contributing to the mechanism by which estrogen triggers the hypercoagulability state and increased risk for venous thrombosis in women undergoing oral EPT. PMID- 22089179 TI - Effects of yoga exercise on serum adiponectin and metabolic syndrome factors in obese postmenopausal women. AB - OBJECTIVE: Regular and continuous yoga exercise is one of the most important nonpharmacological methods of improving serum lipid concentrations, adipose tissue, and metabolic syndrome factors. The purpose of this study was to analyze the effects of yoga exercise on serum adiponectin and metabolic syndrome factors in obese postmenopausal Korean women. METHODS: Sixteen healthy postmenopausal women aged 54.50 +/- 2.75 years with more than 36% body fat were randomly assigned to either a yoga exercise group (n = 8) or to a "no exercise" control group (n = 8). The variables of body composition, visceral fat, serum adiponectin, and metabolic syndrome factors were measured in all the participants before and after the 16-week study. RESULTS: Body weight, percentage of body fat, lean body mass, body mass index, waist circumference, and visceral fat area had significantly decreased. High-density lipoprotein cholesterol and adiponectin had significantly increased, but total cholesterol, triglyceride, low-density lipoprotein cholesterol, blood pressure, insulin, glucose, and homoeostasis model assessment-insulin resistance had significantly decreased. Serum adiponectin concentrations were significantly correlated with waist circumference, high density lipoprotein cholesterol, diastolic blood pressure, and homoeostasis model assessment-insulin resistance in the postyoga exercise group. CONCLUSIONS: Our findings indicate that yoga exercise improves adiponectin level, serum lipids, and metabolic syndrome risk factors in obese postmenopausal women. Consequently, yoga exercise will be effective in preventing cardiovascular disease caused by obesity in obese postmenopausal Korean women. PMID- 22089180 TI - Antioxidant enzymes GSR, SOD1, SOD2, and CAT gene variants and bone mineral density values in postmenopausal women: a genetic association analysis. AB - OBJECTIVE: Oxidative stress participates in decreasing bone formation and stimulating bone resorption. Furthermore, antioxidant enzymes have been observed to have low protective activity in women with osteoporosis.The aim of the present study was to examine any association of selected gene polymorphisms of the glutathione S-reductase (GSR), superoxide dismutase (SOD1 and SOD2), and catalase (CAT) genes, alone or in combination, with the bone mineral density (BMD) values of femoral neck (fn), lumbar spine (ls), and total hip (th) in Slovenian postmenopausal women. METHODS: The gene polymorphisms of CAT, GSR, SOD1, and SOD2 genes in 468 postmenopausal women were analyzed using restriction fragment length polymorphism and a fluorescent 5'-exonuclease genotyping method. BMD_fn, BMD_ls, and BMD_th were measured using dual-energy x-ray absorptiometry. Moreover, univariate statistic analysis and two-way analysis of variance for interaction testing were performed. RESULTS: A significant association of BMD_th values (P = 0.027) was found in genotype subgroups of 423-287G>A GSR polymorphism located in the third intron among postmenopausal women. Furthermore, women with at least one G allele showed significantly higher levels of BMD_fn (P = 0.044), BMD_th (P = 0.009), and BMD_ls (P = 0.043) than those that are AA homozygotes. Interestingly, the 423-287G>A_GSR*1154-393T>A_GSR combination was significantly associated with BMD_fn (P = 0.013) and BMD_th (P = 0.002) in postmenopausal women. CONCLUSIONS: The results of our study demonstrate for the first time that antioxidant enzyme GSR gene polymorphisms are significantly associated with BMD, suggesting that the A allele of 423-287G>A GSR polymorphism could contribute to decreased BMD values in postmenopausal women. PMID- 22089181 TI - Behavioral compensatory adjustment to exercise intervention. PMID- 22089182 TI - Age and postmenopausal bleeding risk factors for malignant changes in endometrial polyps. PMID- 22089183 TI - Effects of excess body mass on strength and fatigability of quadriceps in postmenopausal women. AB - OBJECTIVE: Obesity is a major public health problem leading to, among other things, reduced functional capacity. Moreover, obesity-related declines in functional capacity may be compounded by the detrimental consequences of menopause. The aim of this study was to understand the potential effects of excess body mass on measures of functional capacity in postmenopausal women. METHODS: Forty-five postmenopausal women aged 50 to 60 years were divided into two groups according to body mass index (BMI): obese (BMI, >= 30 kg/m(2); n = 19) and nonobese (BMI, 18.5-29.9 kg/m(2); n = 26). To determine clinical characteristics, body composition, bone mineral density, and maximal exercise testing was performed, and a 3-day dietary record was estimated. To assess quadriceps function, isokinetic exercise testing at 60 degrees per second (quadriceps strength) and at 300 degrees per second (quadriceps fatigue) was performed. RESULTS: The absolute value of the peak torque was not significantly different between the groups; however, when the data were normalized by body mass and lean mass, significantly lower values were observed for obese women compared with those in the nonobese group (128% +/- 25% vs 155% +/- 24% and 224% +/- 38% vs 257% +/- 47%, P < 0.05). The fatigue index did not show any significant difference for either group; however, when the data were normalized by the body mass and lean mass, significantly lower values were observed for obese women (69% +/- 16% vs 93% +/- 18% and 120% +/- 25% vs. 135% +/- 23%, P < 0.01). CONCLUSIONS: Our results show that despite reduced muscle force, the combination of obesity and postmenopause may be associated with greater resistance to muscle fatigue. PMID- 22089184 TI - Postreperfusion cardiac arrest and resuscitation during orthotopic liver transplantation: dynamic visualization and analysis of physiologic recordings. AB - We recently reported on the Multi Wave Animator (MWA), a novel open-source tool with capability of recreating continuous physiologic signals from archived numerical data and presenting them as they appeared on the patient monitor. In this report, we demonstrate for the first time the power of this technology in a real clinical case, an intraoperative cardiopulmonary arrest following reperfusion of a liver transplant graft. Using the MWA, we animated hemodynamic and ventilator data acquired before, during, and after cardiac arrest and resuscitation. This report is accompanied by an online video that shows the most critical phases of the cardiac arrest and resuscitation and provides a basis for analysis and discussion. This video is extracted from a 33-min, uninterrupted video of cardiac arrest and resuscitation, which is available online. The unique strength of MWA, its capability to accurately present discrete and continuous data in a format familiar to clinicians, allowed us this rare glimpse into events leading to an intraoperative cardiac arrest. Because of the ability to recreate and replay clinical events, this tool should be of great interest to medical educators, researchers, and clinicians involved in quality assurance and patient safety. PMID- 22089186 TI - Divergent effects of activated neutrophils on inflammation, Kupffer cell/splenocyte activation, and lung injury following blunt chest trauma. AB - Polymorphonuclear granulocytes (PMNs) have been attributed a primarily deleterious role in the pathogenesis of acute lung injury (ALI). However, evidence exists that PMNs might also act beneficially in certain types of ALI. In this regard, we investigated the role of activated neutrophils in the pathophysiology of lung contusion-induced ALI. We used the model of blunt chest trauma accompanied by PMN-depletion in male C3H/HeN mice. Animals received 25 MUg/g body weight PMN-depleting antibody Gr-1 intravenously 48 h before trauma. Bronchoalveolar lavage (BAL) and lung tissue interleukin 6 (IL-6) were similarly elevated in PMN-depleted and control animals after trauma, whereas macrophage inflammatory protein 2 and monocyte chemoattractant protein 1 in BAL and lungs, IL-10 in BAL, and lung keratinocyte chemoattractant (KC) were even further increased in the absence of PMNs. Plasma IL-6 and KC were also increased in response to the insult and even further in the absence of PMNs. Chest trauma induced an enhanced release of IL-6, tumor necrosis factor alpha, macrophage inflammatory protein 2, monocyte chemoattractant protein 1, and IL-10 from isolated KU, which was blunted in the absence of PMNs. In the presence of PMNs, BAL protein was further increased at 30 h when compared with the 3-h time point, which was not the case in the absence of PMNs. Taken together, in response to lung trauma, activated neutrophils control inflammation including mediator release from distant immune cells but simultaneously mediate pulmonary tissue damage. Thus, keeping in mind potential inflammatory adverse effects, modulation of neutrophil activation or trafficking might be a reasonable therapeutic approach in chest trauma-induced lung injury. PMID- 22089187 TI - Plasma levels of liver-specific miR-122 is massively increased in a porcine cardiogenic shock model and attenuated by hypothermia. AB - Tissue-specific circulating micro-RNAs (miRNAs) are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model, we investigated the release pattern of cardiac-specific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. Pigs were anesthetized, and cardiogenic shock was induced by inflation of a percutaneous coronary intervention balloon in the proximal left anterior descending artery for 40 min followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33 degrees C, n = 6) or normothermia (38 degrees C, n = 6). Circulating miRNAs were extracted from plasma and measured with quantitative real-time polymerase chain reaction (PCR). Tissue specificity was assessed by miRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific, whereas miR-208b was expressed exclusively in the heart. In the control group, ischemic cardiogenic shock induced a 460,000-fold and a 63,000-fold increase in plasma levels of miR-122 (P < 0.05) and miR-208b (P < 0.05), respectively. Therapeutic hypothermia significantly diminished the increase in miR-122 compared with the normothermic group (P < 0.005). In our model, hypothermia was initiated after coronary reperfusion and did not affect either myocardial damage as previously assessed by magnetic resonance imaging or the plasma level of miR-208b. Our results indicate that liver-specific miR-122 is released into the circulation in the setting of cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122. PMID- 22089188 TI - Clinical outcome of critically ill patients cannot be defined by cutoff values of monocyte human leukocyte antigen-DR expression. AB - Septic shock is the most common cause of death in intensive care units. During the last two decades, new strategies have focused on the diagnosis and on the immunological changes in critically ill patients. There have been conflicting reports whether monocyte human leukocyte antigen (HLA) DR expression poses a useful parameter to characterize clinical outcome of these patients. To elucidate the role of monocyte HLA-DR expression, we hypothesized that low expression of HLA-DR on circulating human monocytes in critically ill patients correlates with higher mortality and that cutoff values of HLA-DR discriminate surviving from nonsurviving patients. In this retrospective study, monocyte HLA-DR expression in 413 critically ill patients was investigated during their intensive care unit stay. Human leukocyte antigen DR was determined in a quantitative and standardized procedure by flow cytometry (anti-HLA-DR monoclonal antibodies bound per cell [mABs/cell]) at least every third day or when clinical changes in the patients conditions were observed. Healthy probands served as control group to determine the range of "normal" values. As expected, HLA-DR expression was significantly higher in the group of survivors (n = 279) than in the group of nonsurvivors (n = 134; mABs/cell: 23,038 [SD, 11,150] vs. 18,070 [SD, 8,906]; P < 0.001). When minimal HLA-DR values per patient were compared, no cutoff values could be identified between the groups of survivors and nonsurvivors (mABs/cell: 19,611 [SD, 11,129] vs. 14,944 [SD, 8,013]; P < 0.001). In conclusion, in this sizable cohort we could again show that HLA-DR expression is decreased in critically ill patients but it is not suitable as a prognostic or predictive parameter for clinical outcome. PMID- 22089189 TI - Neutralization of IL-10 restores the downregulation of IL-18 receptor on natural killer cells and interferon-gamma production in septic mice, thus leading to an improved survival. AB - The objective of the study was to investigate the mechanisms of insufficient interferon-gamma (IFN-gamma) response to interleukin 18 (IL-18) and the treatment for the insufficient response in septic mice. Interleukin 18 stimulation does not restore IFN-gamma production by blood mononuclear cells in septic patients but does restore its production in postoperative patients. Although sepsis impairs the IFN-gamma response to IL-18, little is known about why the IL-18/IFN-gamma mediated immune response is ineffective in patients with sepsis. A cecal ligation and puncture was made in C57BL/6 mice following a sublethal lipopolysaccharide challenge to examine their IFN-gamma response to IL-18, focusing on natural killer (NK) cells and cytokines. We next examined the effect of neutralization of IL-10 on the NK cell and survival in septic mice. Interleukin 18 injection did not restore IFN-gamma production in septic (cecal ligation and puncture) mice. Despite an increase in the numbers of liver NK cells, the IL-18 receptor (IL-18R) expression was decreased in the septic mice compared with sham mice. Serum IL-10 levels were positively correlated with the percentage of liver NK cells, but negatively with their IL-18R expression. Neutralization of IL-10 restored the IL 18R expression on liver NK cells and restored the IFN-gamma response in the septic mice, improving their survival. Sepsis might impair IL-18R expression on liver and spleen NK cells and impair the IL-18-mediated IFN-gamma response. Neutralization of IL-10 may restore this response in septic hosts, thereby improving survival. PMID- 22089190 TI - 17beta-estradiol attenuates reduced-size hepatic ischemia/reperfusion injury by inhibition apoptosis via mitochondrial pathway in rats. AB - The aim of this study was to investigate the effect of 17beta-estradiol (E2) on hepatocyte apoptosis after reduced-size hepatic ischemia/reperfusion (I/R) injury and its mechanism. A rat model of reduced-size hepatic I/R injury was established. Sprague-Dawley rats were randomly allocated into sham, I/R, and E2 + I/R group. 17beta-Estradiol (4 mg/kg) or the vehicle was administered i.p. 1 h before ischemia and immediately after operation. For each group, 10 rats were used to investigate the survival during a week after reperfusion. Blood samples and liver tissues were obtained in the remaining animals after 3, 6, 12, and 24 h of reperfusion to assess serum aspartate aminotransferase and alanine aminotransferase levels, liver tissue malondialdehyde concentration, superoxide dismutase activity, and histopathologic changes. Apoptosis ratio; expression of cytochrome c, Bcl-2, and Bax proteins; and enzymatic activities of caspase 9 and caspase 3 were performed in the samples at 12 h after reperfusion. The serum aspartate aminotransferase and alanine aminotransferase levels and tissue malondialdehyde concentration were increased in the I/R group, whereas the increase was significantly reduced by E2. The superoxide dismutase activity, depressed by I/R injury, was elevated back to normal levels by treatment with E2. Severe hepatic damage was observed by light microscopy in the I/R group, whereas administration of E2 resulted in tissue and cellular preservation. Furthermore, E2 inhibited hepatocellular apoptosis by upregulating the ratio of Bcl-2 and Bax expression, reduced cytosolic cytochrome c level, and decreased caspase 9 and caspase 3 activities. The 7-day survival rate was significantly higher in the E2 + I/R group than in the I/R group. These results indicated that E2 protects liver tissues from reduced-size hepatic I/R injury by suppressing mitochondrial apoptotic pathways. PMID- 22089191 TI - Inhaled hydrogen sulfide induces suspended animation, but does not alter the inflammatory response after blunt chest trauma. AB - The treatment of acute lung injury and septic complications after blunt chest trauma remains a challenge. Inhaled hydrogen sulfide (H2S) may cause a hibernation-like metabolic state, which refers to an attenuated systemic inflammatory response. Therefore, we tested the hypothesis that inhaled H2S induced suspended animation may attenuate the inflammation after pulmonary contusion. Male Sprague-Dawley rats were subjected to blunt chest trauma (blast wave) or sham procedure and subsequently exposed to a continuous flow of H2S (100 ppm) or control gas for 6 h. Body temperature and activity were measured by an implanted transmitter. At 6, 24, or 48 h after trauma, animals were killed, and the cellular contents of bronchoalveolar lavage (BAL) as well as cytokine concentrations in BAL, plasma, and culture supernatants of blood mononuclear cells, Kupffer cells, splenic macrophages, and splenocytes were determined. Hydrogen sulfide inhalation caused a significant reduction in body temperature and activity. The trauma-induced increase in alveolar macrophage counts was abrogated 48 h after trauma when animals received H2S, whereas the trauma-induced increase in neutrophil counts was unaltered. Furthermore, H2S inhalation partially attenuated the mediator release in BAL and culture supernatants of Kupffer cells as well as splenic cells; it altered plasma cytokine concentrations but did not affect the trauma-induced changes in mononuclear cell culture supernatants. These findings indicate that inhaled H2S induced a reduced metabolic expenditure and partially attenuated inflammation after trauma. Nevertheless, in contrast to hypoxic- or pathogen-induced lung injury, H2S treatment appears to have no protective effect after blunt chest trauma. PMID- 22089193 TI - Increased granzyme levels in cytotoxic T lymphocytes are associated with disease severity in emergency department patients with severe sepsis. AB - Exocytosis of granules containing the cytolytic effector (CE) molecules granzyme A (GzmA), granzyme B (GzmB), and perforin is one major pathway of lymphocyte mediated cytotoxicity. Studies in murine models and the finding of elevated granzyme levels in the plasma of septic patients have implicated cytotoxic lymphocytes in the pathogenesis of sepsis. We sought to evaluate the role of cytotoxic cells and CE in sepsis and determine if intracellular levels of CE in cytotoxic cells correlate with disease severity. We conducted a prospective cohort study of 40 patients enrolled into one of three groups: controls (C), acutely ill nonseptic illnesses, or patients with severe sepsis (SS) (lactate, >4 mmol/L; systolic blood pressure, <90 mmHg after 2 L normal saline). Peripheral blood mononuclear cells were isolated and stained for extracellular markers for defined subpopulations and for intracellular expression of GzmA and GzmB and perforin. Levels of CE were quantified by geometric mean fluorescent intensity (GMFI) via flow cytometry. Cytotoxic T lymphocyte (CTL) expression was higher in SS (P = 0.04). The GMFI of GzmB was significantly higher in CTLs of SS patients versus acutely ill nonseptic illnesses or C. The GMFI of each GzmA and GzmB in CTLs were associated with the Acute Physiology and Chronic Health Evaluation II score (P = 0.01). A significant increase in the number of granulocytes in the peripheral blood mononuclear cells of SS patients consisted primarily of low density neutrophils, which expressed increased levels of GzmA (P < 0.01). The results suggest that CTLs are activated in SS and express significantly higher intracellular levels of GzmB and that GzmA and B levels correlate with disease severity. PMID- 22089192 TI - Reduced peroxisome proliferator-activated receptor alpha expression is associated with decreased survival and increased tissue bacterial load in sepsis. AB - The peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a member of the nuclear receptor family with many important physiologic roles related to metabolism and inflammation. Previous research in pediatric patients with septic shock revealed that genes corresponding to the PPAR-alpha signaling pathway are significantly downregulated in a subgroup of children with more severe disease. In this study, PPAR-alpha expression analysis using whole-blood derived RNA revealed that PPAR-alpha expression was decreased in patients with septic shock and that the magnitude of that decrement correlated with the severity of disease. In a mouse model of sepsis, induced by cecal ligation and puncture, knockout mice lacking PPAR-alpha had decreased survival compared with wild-type animals. Plasma cytokine analysis demonstrated decreased levels of interleukin 1beta (IL-1beta), IL-6, IL-17, keratinocyte-derived cytokine, macrophage chemoattractant protein 1, macrophage inflammatory protein 2, and tumor necrosis factor alpha at 24 h in PPAR-alpha knockout animals. Cell surface markers of activation on splenic dendritic cells, macrophages, and CD8 T cells were reduced in PPAR-alpha null animals, and the bacterial load in lung and splenic tissues was increased. These data indicate that reduced or absent PPAR-alpha expression confers a survival disadvantage in sepsis and that PPAR-alpha plays a role in maintaining appropriate immune functions during the sepsis response. PMID- 22089194 TI - Paeonol attenuates microglia-mediated inflammation and oxidative stress-induced neurotoxicity in rat primary microglia and cortical neurons. AB - Inflammation and oxidative stress play important roles in the pathogenesis of neurodegenerative disorders such as stroke, traumatic injury, Parkinson disease, and Alzheimer disease. Paeonol, a natural compound extracted from Moutan cortex, is a potent anti-inflammatory and antioxidative agent. The aim of this study was to investigate the neuroprotective mechanisms of paeonol on lipopolysaccharide (LPS)-induced inflammation in rat primary microglia and 6-hydroxydopamine-induced oxidative damage in cortical neurons. In LPS-treated microglia, paeonol attenuated the overexpression of inducible nitric oxide synthase and cyclooxygenase 2, leading to the decrease in nitric oxide and prostaglandin E2 production, respectively. Paeonol also suppressed LPS-induced phosphorylation of extracellular signal-regulated kinase and Jun N-terminal kinase. In addition, LPS stimulated NADPH oxidase activation and reactive oxygen species production were attenuated by paeonol. Paeonol-induced upregulation of heme oxygenase 1 was also observed. Moreover, paeonol attenuated LPS-treated microglia culture medium induced neuron cells death. Posttreatment with paeonol also reduced inflammatory responses in LPS-activated microglia and increased cell viability in LPS-treated microglia culture medium-treated neurons. Furthermore, in 6-hydroxydopamine treated cortical neurons, paeonol not only decreased reactive oxygen species production but also increased cell viability, superoxide dismutase activity, and the antiapoptotic protein B-cell lymphoma 2 expression. Taken together, the present results suggest that paeonol might be a potential neuroprotective agent via inhibiting microglia-mediated inflammation and oxidative stress-induced neuronal damage. PMID- 22089195 TI - Acute effects of balanced versus unbalanced colloid resuscitation on renal macrocirculatory and microcirculatory perfusion during endotoxemic shock. AB - This study was designed to investigate the acute effects of balanced versus unbalanced colloid resuscitation on renal macrocirculatory and microcirculatory perfusions during lipopolysaccharide-induced endotoxemic shock in rats. We tested the hypothesis that balanced colloid resuscitation would be better for the kidney than unbalanced colloid resuscitation. Shock was induced by lipopolysaccharide (10 mg/kg i.v. over 30 min). When mean arterial pressure (MAP) was decreased to 40 mmHg, fluid resuscitation was started with either hydroxyethyl starch (HES130/0.42) dissolved in saline (HES-NaCl) as an unbalanced colloid solution or HES130/0.42 dissolved in Ringer's acetate (HES-RA) as a balanced colloid solution. Microvascular perfusion in the renal cortex was monitored using laser speckle imaging, and in addition, systemic hemodynamics, renal artery blood flow (RBF), and plasma ion levels were measured. Shock decreased MAP, led to anuria, and worsened all other parameters. Hydroxyethyl starch-NaCl improved MAP (P > 0.05) but did not improve RBF (P > 0.05), metabolic acidosis (P > 0.05), and plasma ion levels (P > 0.05). Hydroxyethyl starch-RA improved MAP (P < 0.05), RBF (P < 0.05), and renal microvascular perfusion (P < 0.05), but did not improve metabolic acidosis (P > 0.05) and plasma ion levels (P > 0.05). Both HES-NaCl and HES-RA treatment could normalize creatinine clearance but not fractional sodium excretion. In endotoxemic rats, balanced colloid (HES) resuscitation was shown to be superior to unbalanced colloid resuscitation in terms of improvement of renal macrovascular and microvascular perfusions. However, whether this results in improved renal function in the long term warrants further study. PMID- 22089196 TI - The decline of autophagy contributes to proximal tubular dysfunction during sepsis. AB - Severe sepsis associated with overproduction of tumor necrosis factor alpha and reactive oxygen species leads to energy depletion and cellular damage. Both reactive oxygen species and damaged organelles induce autophagy for recycling nutrients to combat pathological stress. To study whether autophagy plays a beneficial role in the pathogenesis of renal failure during sepsis, rats were subjected to cecal ligation and puncture (CLP) or sham operation. Temporal relationship of autophagy and renal dysfunction were examined in vivo. The results showed that the level of lipidated microtubule-associated protein light chain 3 (LC3-II), a marker of autophagy, elevated transiently at 3 h but declined at 9 h until 18 h after CLP. Light chain 3 aggregation in renal tissue showed a similar trend to the change of LC3-II protein. High levels of blood urea nitrogen and creatinine as well as low tubular sodium reabsorption occurred at 18 h after CLP. The distribution of autophagy located primarily in angiotensin-converting enzyme-positive, which is concentrated in proximal tubule, but calbindin D28k (calcium-binding protein D28K, a marker of distal tubule)-negative cells in renal cortex. Therefore, NRK-52E (proximal tubule epithelial cell line) cells were used to further examine cell viability and DNA fragmentation after silencing or inducing autophagy. We found that knockdown of Atg7 (autophagy-related gene 7) exaggerates, whereas preincubation of rapamycin (an autophagy inducer) diminishes tumor necrosis factor alpha-induced cell death. These results suggest that the decline of sepsis-induced autophagy contributes to the proximal tubular dysfunction, and maintenance of sufficient autophagy prevents cell death. These data open prospects for therapies that activate autophagy during sepsis. PMID- 22089197 TI - beta-Catenin dynamics in the regulation of microvascular endothelial cell hyperpermeability. AB - beta-Catenin, a key regulator of barrier integrity, is an important component of the adherens junctional complex. Although the roles of beta-catenin in maintaining the adherens junctions and Wnt signaling are known, the dynamics of beta-catenin following insult and its potential role in vascular recovery/repair remain unclear. Our objective was to define beta-catenin's dynamics following disruption of the adherens junctional complex and subsequent recovery. Rat lung microvascular endothelial cells were treated with active caspase 3 enzyme, by protein transference method, as an inducer of junctional damage and permeability. The disruption and subsequent recovery of beta-catenin to the adherens junctions were studied via immunofluorescence. Rat lung microvascular endothelial cell monolayers were used to measure hyperpermeability. To understand the role of beta catenin on nuclear translocation/transcriptional regulation in relationship to the recovery of the adherens junctions, Tcf-mediated transcriptional activity was determined. Active caspase 3 induced a loss of beta-catenin at the adherens junctions at 1 and 2 h followed by its recovery at 3 h. Transference of Bak peptide, an inducer of endogenous caspase 3 activation, induced hyperpermeability at 1 h followed by a significant decrease at 2 h. Inhibition of GSK-3beta and the transfection of beta-catenin vector increased Tcf-mediated transcription significantly (P < 0.05). The dissociated adherens junctional protein beta catenin translocates into the cytoplasm, resulting in microvascular hyperpermeability followed by a time-dependent recovery and relocation to the cell membrane. Our data suggest a recycling pathway for beta-catenin to the cell junction. PMID- 22089198 TI - Disruption of the mucosal barrier during gut ischemia allows entry of digestive enzymes into the intestinal wall. AB - Intestinal ischemia is associated with high morbidity and mortality, but the underlying mechanisms are uncertain. We hypothesize that during ischemia the intestinal mucosal barrier becomes disrupted, allowing digestive enzymes access into the intestinal wall initiating autodigestion. We used a rat model of splanchnic ischemia by occlusion of the superior mesenteric and celiac arteries up to 30 min with and without luminal injection of tranexamic acid as a trypsin inhibitor. We determined the location and activity of digestive proteases on intestinal sections with in situ zymography, and we examined the disruption of two components of the mucosal barrier: mucin isoforms and the extracellular and intracellular domains of E cadherin with immunohistochemistry and Western blot techniques. The results indicate that nonischemic intestine has low levels of protease activity in its wall. After 15-min ischemia, protease activity was visible at the tip of the villi, and after 30 min, enhanced activity was seen across the full thickness of the intestinal wall. This activity was accompanied by disruption of the mucin layer and loss of both intracellular and extracellular domains of E cadherin. Digestive protease inhibition in the intestinal lumen with tranexamic acid reduced morphological damage and entry of digestive enzymes into the intestinal wall. This study demonstrates that disruption of the mucosal epithelial barrier within minutes of intestinal ischemia allows entry of fully activated pancreatic digestive proteases across the intestinal barrier triggering autodigestion. PMID- 22089199 TI - Protective effects of exogenous interleukin 18-binding protein in a rat model of acute renal ischemia-reperfusion injury. AB - Ischemia-reperfusion (I/R) renal injury is considered the most common cause of acute kidney injury (AKI). The pathophysiology of I/R AKI involves a complex interplay among tubular epithelial cell injury, microcirculation dysfunction, and inflammation. Interleukin 18-binding protein (IL-18BP) is a natural inhibitor of IL-18 a cytokine that plays an important role in the pathogenesis of AKI. Therefore, we hypothesized that exogenous IL-18BP could protect against renal injuries after kidney I/R. Male Sprague-Dawley rats were divided into three groups: a sham operation group, I/R with vehicle injection, and I/R with IL-18BP injection. Rats underwent bilateral renal pedicle clamping, and IL-18BP or vehicle was administered just before reperfusion. Rats were killed 6, 24, and 72 h after reperfusion. After IL-18BP treatment, renal tubule epithelium showed reduced apoptosis and enhanced proliferation. For peritubular capillary (PTC) endothelium, apoptosis was inhibited, and there was an increase in PTC endothelium density. Macrophage infiltration was inhibited, and inflammatory cytokines were downregulated. Increased expression of vascular endothelial growth factor and decreased expression of thrombospondin 1 were also observed. Exogenous IL-18BP attenuated renal injury caused by I/R via inhibiting inflammation in the renal tissue and protecting tubular epithelium and PTC endothelium. PMID- 22089200 TI - Combined recombinant human activated protein C and ceftazidime prevent the onset of acute respiratory distress syndrome in severe sepsis. AB - This experimental animal study investigates the effects of combined recombinant human activated protein C (rhAPC) and ceftazidime on cardiopulmonary function in acute lung injury and severe sepsis. Twenty-one sheep (37 +/- 2 kg) were operatively prepared and randomly allocated to either the sham, control, or treatment group (n = 7 each). Single treatments of rhAPC or ceftazidime were published previously; therefore, control groups were dispensed in the present study, what may be considered a study limitation. Acute lung injury and sepsis were induced according to an established protocol. The sham group received only the vehicle. The sheep were studied in awake state for 24 h and mechanically ventilated. Recombinant human APC (continuous infusion 24 MUg/kg per hour) and ceftazidime (3-g bolus at 1 and 13 h) were intravenously administered. The animals were fluid resuscitated with Ringer's lactate to maintain hematocrit at baseline. Compared with injured controls, the treatment group had a significantly higher PaO2/FIO2 ratio, and the onset of acute respiratory distress syndrome was prevented. The increase in pulmonary microvascular shunt fraction and airway obstruction in bronchi and bronchiole, as well as lung 3-nitrotyrosine, lung myeloperoxidase, cardiac 3-nitrotyrosine, and cardiac malondialdehyde levels, was significantly reduced as compared with controls (P < 0.05 each). Treated sheep had significantly improved hemodynamics as reflected by mean arterial pressure, heart rate, cardiac index, and systemic vascular resistance index (P < 0.05 each). In addition, plasma oncotic pressure and urine output were significantly improved (P < 0.05 each). Combined rhAPC and ceftazidime significantly improved cardiopulmonary function, reduced pulmonary and cardiac tissue injury, and prevented the onset of acute respiratory distress syndrome in ovine severe sepsis without obvious adverse effects. PMID- 22089201 TI - Proinflammatory chemokines in the intestinal lumen contribute to intestinal dysfunction during endotoxemia. AB - Intestinal failure is common in patients with septic shock, with dysfunction of the gut often manifesting as both a cause and consequence of their critical illness. Most studies investigating the pathogenesis of intestinal failure focus on the systemic aspect, although few data examine the inflammatory signaling in the intestinal lumen. Having previously demonstrated apical/luminal chemokine secretion in an in vitro model of intestinal inflammation, we hypothesized that endotoxemia would induce secretion of proinflammatory chemokines into the intestinal lumen. In addition, we examined the contribution of these mediators to intestinal dysmotility. C57/BL6 male mice were injected intraperitoneally with LPS. Serum, intestinal tissue, and intestinal luminal contents were harvested for cytokine analysis. For intestinal motility studies, a transit assay was performed after oral gavage of chemokines. Caco-2 cells grown on Transwell culture inserts were used to examine the role of the intestinal epithelium in chemokine secretion. Monocyte chemoattractant protein 1 (MCP-1/CCL2) and macrophage-derived chemokine (MDC/CCL22) were secreted into the lumen of multiple segments of the gut during endotoxemia in mice. In vitro work showed that the intestinal epithelium participates in monocyte chemoattractant protein 1 and MDC secretion and expresses the CCR2 and CCR4 receptors for these chemokines. Intestinal transit studies show that oral gavage of MDC results in impaired gut motility. This study demonstrates that the intestinal lumen is an active compartment in the gut's inflammatory response. Proinflammatory chemokines are secreted into the intestinal lumen during endotoxemia. These intraluminal chemokines contribute to intestinal dysmotility, complicating intestinal failure. PMID- 22089202 TI - The transcutaneous oxygen challenge test: a noninvasive method for detecting low cardiac output in septic patients. AB - The transcutaneous partial pressure of oxygen (PtcO2) index has been used to detect low-flow state in circulatory failure, but the value of the transcutaneous oxygen challenge test (OCT) to estimate low cardiac output has not been thoroughly evaluated. The prospective observational study examined 62 septic patients requiring PiCCO-Plus for cardiac output monitoring. Simultaneous basal blood gases from the arterial, central venous catheters were obtained. Cardiac indices were measured by the transpulmonary thermodilution technique at the same time, then the 10-min inspired 1.0 fractional inspired oxygen concentration (FIO2) defined as the OCT was performed. Transcutaneous partial pressure of oxygen was measured continuously by using a noninvasive transcutaneous monitor throughout the test. The values for arterial pressure of oxygen (PaO2) were examined on inspired of 1.0 FIO2. We calculated the PtcO2 index = (baseline PtcO2/baseline PaO2), 10-min OCT (10 OCT) = (PtcO2 after 10 min on inspired 1.0 O2) - (baseline PtcO2), and the oxygen challenge index = (10 OCT) / (PaO2 on inspired 1.0 O2 - baseline PaO2). Patients were divided into two groups: a normal cardiac index (CI) group with CI of greater than 3 L/min per m (n = 41) and a low CI group with CI of 3 L/min per m or less (n = 21). The 10 OCT and the oxygen challenge index predicted a low CI (<= 3 L/min per m) with an accuracy that was similar to central venous oxygen saturation, which was significantly better than the PtcO2 index. For a 10 OCT value of 53 mmHg, sensitivity was 0.83; specificity, 0.86; a positive predictive value, 0.92; and a negative predictive value, 0.72 for detecting CI of 3 L/min per m or less. We propose that the OCT substituted for the PtcO2 index as an accurate alternative method of PtcO2 for revealing low CI in septic patients. PMID- 22089203 TI - Differential sensitivity to LPS-induced myocardial dysfunction in the isolated brown Norway and Dahl S rat hearts: roles of mitochondrial function, NF-kappaB activation, and TNF-alpha production. AB - Recently, we reported that Brown Norway (BN) rats were more resistant to lipopolysaccharide (LPS)-induced myocardial dysfunction than Dahl S (SS) rats. This differential sensitivity was exemplified by reduced production of proinflammatory cytokines and diminished nuclear factor-kappaB pathway activation. To further clarify the mechanisms of different susceptibility of these two strains to endotoxin, this study was designed to examine the alterations of cardiac and mitochondrial bioenergetics, proinflammatory cytokines, and signaling pathways after hearts were isolated and exposed to LPS ex vivo. Isolated BN and SS hearts were perfused with LPS (4 MUg/mL) for 30 min in the Langendorff preparation. Lipopolysaccharide depressed cardiac function as evident by reduced left ventricular developed pressure and decreased peak rate of contraction and relaxation in SS hearts but not in BN hearts. These findings are consistent with our previous in-vivo data. Under complex I substrates, a higher oxygen consumption and hydrogen peroxide (H2O2) production were observed in mitochondria from SS hearts than those from BN hearts. Lipopolysaccharide significantly increased H2O2 levels in both SS and BN heart mitochondria; however, the increase in oxygen consumption and H2O2 production in BN heart mitochondria was much lower than that in SS heart mitochondria. In addition, LPS significantly decreased complex I activity in SS hearts but not in BN hearts. Furthermore, LPS induced higher levels of tumor necrosis factor-alpha and increased phosphorylation of IkappakappaB and p65 more in SS hearts than in BN hearts. Our results clearly demonstrate that less mitochondrial dysfunction combined with a reduced production of tumor necrosis factor-alpha and diminished activation of nuclear factor-kappaB are involved in the mechanisms by which isolated BN hearts were more resistant to LPS-induced myocardial dysfunction. PMID- 22089204 TI - Homology in systemic neutrophil response induced by human experimental endotoxemia and by trauma. AB - The investigation of the trauma-induced innate immune responses is hampered by the wide variability in patients, type of trauma, and environmental factors. To circumvent this heterogeneity, we examined whether the systemic innate immune response toward human experimental endotoxemia is similar to the response during systemic inflammatory response syndrome after trauma. We tested the hypothesis that the innate immune response to pathogen-associated molecular pattern (e.g., lipopolysaccharides [LPSs]) and danger-associated molecular pattern (as induced by injury) leads to a comparable in vivo activation of human neutrophils. Escherichia coli LPS (2 ng/kg) was injected intravenously in nine healthy volunteers to induce a controlled systemic inflammatory response. Indices of systemic inflammation in this human inflammation model were compared with those of 12 trauma patients with a mean injury severity score of 19. Blood samples were withdrawn at 3 and 24 h after LPS-challenge or injury. Blood samples of nine healthy volunteers were used as control. Receptor expression was measured as readout for neutrophil activation by flow cytometry. Endotoxemia and injury resulted in a comparable activation phenotype of circulating neutrophils. This phenotype was characterized by downregulation of chemokine receptors CXCR1 and CXCR2 and of Fcgamma receptors II and III. A significant difference between both conditions was seen in CD66b expression and for endotoxin resulted in an increased CD66b expression, whereas injury did not. Neutrophil activation was present 3 h after onset of inflammation, both during experimental endotoxemia as well as in trauma patients. Endotoxin and trauma appear to induce a similar neutrophil activation phenotype. PMID- 22089205 TI - Hypertonic fluid administration in patients with septic shock: a prospective randomized controlled pilot study. AB - We assessed the short-term effects of hypertonic fluid versus isotonic fluid administration in patients with septic shock. This was a double-blind, prospective randomized controlled trial in a 15-bed intensive care unit. Twenty four patients with septic shock were randomized to receive 250 mL 7.2% NaCl/6% hydroxyethyl starch (HT group) or 500 mL 6% hydroxyethyl starch (IT group). Hemodynamic measurements included mean arterial blood pressure (MAP), central venous pressure, stroke volume index, stroke volume variation, intrathoracic blood volume index, gastric tonometry, and sublingual microcirculatory flow as assessed by sidestream dark field imaging. Systolic tissue Doppler imaging velocities of the medial mitral annulus were measured using echocardiography to assess left ventricular contractility. Log transformation of the ratio MAP divided by the norepinephrine infusion rate (log MAP/NE) quantified the combined effect on both parameters. Compared with the IT group, hypertonic solution treatment resulted in an improvement in log MAP/NE (P = 0.008), as well as an increase in systolic tissue Doppler imaging velocities (P = 0.03) and stroke volume index (P = 0.017). No differences between the groups were found for preload parameters (central venous pressure, stroke volume variation, intrathoracic blood volume index) or for afterload parameters (systemic vascular resistance index, MAP). Hypertonic solution treatment decreased the need for ongoing fluid resuscitation (P = 0.046). No differences between groups were observed regarding tonometry or the sublingual microvascular variables. In patients with septic shock, hypertonic fluid administration did not promote gastrointestinal mucosal perfusion or sublingual microcirculatory blood flow in comparison to isotonic fluid. Independent of changes in preload or afterload, hypertonic fluid administration improved the cardiac contractility and vascular tone compared with isotonic fluid. The need for ongoing fluid resuscitation was also reduced. PMID- 22089206 TI - Panax quinquefolium saponins reduce myocardial hypoxia-reoxygenation injury by inhibiting excessive endoplasmic reticulum stress. AB - Excessive endoplasmic reticulum stress (ERS) disrupts protein translation, protein folding, and calcium homeostasis and may contribute to ischemia reperfusion injury. Saponins extracted from the stems and leaves of Panax quinquefolium (PQS) protect rat myocardium against ischemia-reperfusion injury, but it is not known if suppression of ERS contributes to cardioprotection. Neonatal rat cardiomyocytes were subjected to hypoxia-reoxygenation (H-R) in the presence of PQS or vehicle. Cell injury and apoptosis were assayed by trypan blue exclusion, lactate dehydrogenase activity, and flow cytometry. In addition, reverse transcriptase-polymerase chain reaction and Western blotting were used to examine mRNA and protein expression of the ERS-related proteins glucose-regulated protein 78, calreticulin, CCAAT/enhancer-binding protein homologous protein, and caspase-12, as well as the apoptosis-associated proteins Bax and Bcl-2. We confirmed that PQS protects cardiomyocytes from H-R-induced injury and apoptotic cell death. Furthermore, PQS suppressed H-R-induced excessive ERS, as evidenced by reduced caspase 12 activation and decreased glucose-regulated protein 78, calreticulin, and CCAAT/enhancer-binding protein homologous protein overexpression. These results indicated that PQS could alleviate H-R injury of cardiomyocytes, which would be probably related to inhibiting excessive ERS induced by H-R. PMID- 22089207 TI - Immunology in the limelight. PMID- 22089209 TI - Provocative exhibits at the Seventeen Gallery. PMID- 22089210 TI - It takes two to tango: a new couple in the family of ubiquitin-editing complexes. PMID- 22089211 TI - Beta-testing NKT cell self-reactivity. PMID- 22089212 TI - A rescue gone wrong. PMID- 22089213 TI - Turning transcription on or off with STAT5: when more is less. PMID- 22089220 TI - Programmed necrosis: backup to and competitor with apoptosis in the immune system. AB - Programmed cell death is essential for the development and maintenance of the immune system and its responses to exogenous and endogenous stimuli. Studies have demonstrated that in addition to caspase-dependent apoptosis, necrosis dependent on the kinases RIP1 and RIP3 (also called necroptosis) is a major programmed cell death pathway in development and immunity. These two programmed cell-death pathways may suppress each other, and necroptosis also serves as an alternative when caspase-dependent apoptosis is inhibited or absent. Here we summarize recent advancements that have identified the molecular mechanisms that underlie necroptosis and explore the mechanisms that regulate the interplay between apoptosis and necroptosis. PMID- 22089221 TI - Validation of questionnaires to estimate adherence to the Mediterranean diet and life habits in older individuals in Southern Spain. AB - OBJECTIVE: The aim of the present study was to determine the nutritional behaviour of an elderly urban population in Southern Spain, estimating their degree of adherence to the Mediterranean. DIET DESIGN: A population-based cross sectional nutritional survey, recruiting a representative sample of elderly inhabitants. The study sample comprised 260 people. The mean age was 73.60 yrs for the men and 72.25 yrs for the women. Around 70% lived with their family. RESULTS: The questionnaires used were first validated by using the Bland-Altman plot and the Wilcoxon test for paired samples. The degree of adherence to the Mediterranean Diet was around 50%, similar to findings in other Mediterranean populations. We highlight the mean consumption of milk and milk products (300-317 g/day) and of fruit/vegetables (250 g/day), which are slightly below recommendations. Our study subjects were all autonomous in their movements and were physically independent: 80% reported that they performed some type of physical activity. CONCLUSION: In this study, both adherence to the Mediterranean Diet and physical activity were considered as components of a healthy life. In summary, a majority of this elderly population was slightly overweight, considered themselves to be in good health. PMID- 22089222 TI - The oldest old: red blood cell and plasma folate in African American and white octogenarians and centenarians in Georgia. AB - OBJECTIVE: To determine the overall folate status of a population-based multi ethnic sample of octogenarians and centenarians and the specific dietary, demographic and physiological factors associated with observed abnormalities. DESIGN: Population-based multiethnic sample of adults aged 80 to 89 and 98 and above. SETTING: Northern Georgia, USA. PARTICIPANTS: Men and women aged 80 to 89 (octogenarians, n = 77) and 98 and older (centenarians, n = 199). ANALYSES: Wilcoxon rank sum tests, and Chi square and logistic regression analyses were used to examine associations of low and high folate status with hematological indicators and other variables of interest. RESULTS: The prevalence of low red blood cell (RBC) folate was low overall, but tended to be higher in centenarians than in octogenarians (6.5% vs. 1.3%, p = 0.058; defined as RBC folate < 317 nmol/L). The risk of having lower RBC folate (< 25th vs. > 25th percentile for RBC folate for 60yr+ in NHANES 1999-2000) was greater in association with vitamin B12 deficiency (OR = 5.36; 95%CI: 2.87-10.01), African American race (OR = 4.29; 95%CI: 2.08-8.83), and residence in a skilled nursing facility (OR = 3.25; 95%CI: 1.56-6.78) but was not influenced by age, gender, B-vitamin supplement use, high/low food score or presence of atrophic gastritis. Combined high plasma folate and low vitamin B12 status was present in some individuals (n=11), but was not associated with increased prevalence of anemia or cognitive impairment in this study. CONCLUSIONS: Low RBC folate status (< 317 nmol/L) was rare in this post folic acid fortification sample of octogenarians and centenarians. RBC folate status (< 25th percentile) was strongly associated with 1) vitamin B12 deficiency, which has strong implications for vitamin treatment, and 2) with being African American, suggesting racial disparities exist even in the oldest old. PMID- 22089223 TI - Older people with diabetes have higher risk of depression, cognitive and functional impairments: implications for diabetes services. AB - OBJECTIVES: To examine the relationship between diabetes and impairments in functional and cognitive status as well as depression in older people. DESIGN: Cross-sectional study. SETTING: Elderly Health Centres (EHC) in Hong Kong. PARTICIPANTS: 66,813 older people receiving baseline assessment at EHC in 1998 to 2001. MEASUREMENTS: Diabetes status was defined by self-report and blood glucose tests. Functional status was assessed by 5 items of instrumental activities of daily living (IADL) and 7 items of activities of daily living (ADL). Cognitive status was screened by the Abbreviated Mental Test-Hong Kong version (AMT). Depressive symptoms were screened by the Geriatric Depression Scale-Chinese version (GDS). RESULTS: Among the subjects, 10.4% reported having regular treatment for diabetes, 3.4% had diabetes but were not receiving regular treatment, and 86.2% did not have diabetes. After controlling for age, sex and education level, those having regular treatment for diabetes were 1.7 times more likely (OR=1.65, 95% CI: 1.51-1.80) to have functional impairment, 1.3 times more likely (OR=1.28, 95% CI: 1.11-1.48) to have cognitive impairment and 1.3 times more likely (OR=1.35, 95% CI: 1.25-1.46) to have depression, than older people without diabetes. CONCLUSION: Older people with diabetes may be less capable of managing the disease than the younger ones as a result of increased risk of both physical and cognitive impairment. This study provided further evidence for the need of an international consensus statement regarding care of diabetes in older people. PMID- 22089224 TI - Oxidative stress, frailty and cognitive decline. AB - The causes of frailty are complex and must be accepted as multidimensional based on the interplay of genetic, biological, physical, psychological, social and environmental factors, although inflammation and oxidative stress are two factors that play an important role in the development of symptoms with those fragile states. OBJECTIVE: to establish the relationship between oxidative stress, frailty and decline cognitive. METHODS: A review of the literature and data abstraction from papers are showing the relationship between a) oxidative stress and frailty, b) oxidative stress and decline cognitive. RESULTS: The papers reviewed showed that we can establish a relationship between the progress of neurodegenerative disorders and increased oxidative stress. Also found in frailty, that oxidative stress plays an important role as one of the starting points for the appearance of permanent inflammatory states. CONCLUSIONS: Although the literature indicates the relationship between oxidative stress, frailty and decline cognitive, more studies are needed in this regard, especially interventions that asses whether increased intake of antioxidants in older frailty may improve the progress of disease and slow cognitive decline. PMID- 22089225 TI - The effects of diet education plus light resistance training on coronary heart disease risk factors in community-dwelling older adults. AB - OBJECTIVES: To examine the effects of diet education (DE) plus light resistance training (RT) on coronary heart disease risk (CHD) factors, specifically dietary quality, blood lipid and C-Reactive protein (CRP) concentrations in overweight and obese older adults in a community setting. DESIGN: Community outreach intervention with a quasi-experimental design. PARTICIPANTS AND SETTING: A total of 96 subjects, 16 males and 80 females, aged 69.2 +/- 6.2 years, community dwelling, and from one of four senior centers in Rhode Island. INTERVENTION: Subjects participated in 30 minutes of DE (once per week) and ~80 minutes of RT (two separate sessions per week) for eight weeks. The DE sessions were led by a registered dietitian. MEASUREMENTS: Anthropometrics (height, weight, waist circumference, hip circumference, and body composition), clinical (blood pressure), biochemical (lipid profile, glucose, and CRP concentrations), and diet quality measured by the Dietary Screening Tool (DST). RESULTS: A significant change was seen in DST risk categories from baseline to post-intervention, chi2 (2)=20.43, p < 0.01. Significant differences were seen in triacylglycerol (p=0.028) as well as in systolic and diastolic blood pressures, weight, waist circumference, hip circumference, percent body fat, fat mass, and body mass index (all p<0.05). CONCLUSION: This intervention effectively decreased CHD risk in overweight and obese older adults. Future research is needed to examine the effects of longer DE plus RT interventions with greater weight loss on the lipid profile and CRP concentrations in overweight and obese older adults at risk for CHD. PMID- 22089226 TI - Nutrition risk factors among home delivered and congregate meal participants: need for enhancement of nutrition education and counseling among home delivered meal participants. AB - OBJECTIVE: The short-term impact of nutrition education and counseling intervention on nutrition risk factors among home delivered (HDM) and congregate (CGM) meal participants using Nutrition Survey Risk Screening was studied. DESIGN: A two-year intervention was conducted with 355 participants (n=259 CGM, n=96 HDM). Various nutrition behaviors that affect the nutrition risk score were compared. SETTING: Congregate and home delivered meal locations in a northern county of New Jersey. PARTICIPANTS: CGM and HDM participants in a northern county of New Jersey age 60 and older. INTERVENTION: CGM participants received regular topical nutrition education and counseling in a classroom format with cooking demo, discussion, and handouts. The HDM participants only received the printed material (same handouts) and counseling by telephone. MEASUREMENTS: Demographics, medical condition, risk factors data were collected. All participants completed the 12 items checklist Nutrition Survey Risk Screening. Nutritional behaviors assessed include number of meals eaten per day, servings of fruits and vegetables and nutrition risk score. A score of 6 or more points was defined as persons at high risk nutritionally. The impact of the intervention was evaluated using ANOVA/chi-square on Nutrition Survey Risk Screening. RESULTS: Nutrition education and counseling intervention improved nutrition risk scores; 5.76 to 5.32 (p=0.14) in CGM, 8.1 to 6.1 (p<0.01) in HDM. A slight improvement in nutrition behaviors was noted: eating >= 2 meals in HDM (76 to 81.6 %, p= .310), eating >= 5 servings of fruits and vegetables in CGM (38 to 41.4 %, p=. 398). CONCLUSION: Appropriate nutrition intervention for both HDM and CGM participants can improve health condition and delay chronic diseases. HDM participants need to be a primary focus for more effective nutrition education and counseling. PMID- 22089227 TI - Senile anorexia in different geriatric settings in Italy. AB - OBJECTIVES: Anorexia is the most frequent modification of eating habits in old age, which may lead to malnutrition and consequent morbidity and mortality in older adults. We aimed to estimate the prevalence and factors associated to anorexia in a sample of Italian older persons living in different settings. Our secondary aim was to evaluate the impact of senile anorexia on nutritional status and on eating habits, as well as on functional status. DESIGN AND SETTING: Observational study in nursing homes, in rehabilitation and acute geriatric wards, and in the community in four Italian regions (Lazio, Sicily, Emilia Romagna, and Veneto). PARTICIPANTS: 526 over 65 years old participants were recruited; 218 free-living subjects, 213 from nursing homes, and 96 patients from rehabilitation and acute geriatric wards in the context of a National Research Project (PRIN) from the Italian Ministry of Instruction, University and Research (2005-067913 "Cause e Prevalenza dell'Anoressia senile"). MEASUREMENTS: Anthropometric and nutritional evaluation, olfactory, chewing, and swallowing capacity, food preferences, cognitive function, functional status, depression, quality of life, social aspects, prescribed drugs, and evaluation of gastrointestinal symptoms and pain. Laboratory parameters included prealbumin, albumin, transferrin, C-reactive protein, mucoprotein, lymphocyte count, as well as neurotransmitters leptin, and ghrelin. Anorexia was considered as >=50% reduction in food intake vs. a standard meal (using 3-day "Club Francophone de Geriatrie et Nutrition" form), in absence of oral disorders preventing mastication. RESULTS: The overall prevalence of anorexia was 21.2% with higher values among hospitalized patients (34.1% women and 27.2% men in long-term facilities; 33.3% women and 26.7% men in rehabilitation and geriatric wards; 3.3% women and 11.3% men living in the community) and in the oldest persons. Anorexic subjects were significantly less self-sufficient and presented more often a compromised nutritional and cognitive status. Diet composition analyses of anorexic older adults revealed a lower intake of all food groups and a general tendency to a monotonous diet. CONCLUSION: Anorexia is a frequent condition in older Italians, particularly those hospitalized, with important consequences in the nutritional and functional status. The analysis of dietary components and its quality along with the frequency of intake of single food groups may be useful to plan intervention strategies aiming to improve the nutritional and health status of older adults with anorexia. An early detection of anorexia followed by an adequate intervention in older hospitalized patients to avoid further worsening of clinical and functional status is warranted. PMID- 22089228 TI - Definition of frailty in older men according to questionnaire data (RAND-36/SF 36): The Helsinki Businessmen Study. AB - OBJECTIVE: To explore the association of frailty according to questionnaire data (modified Fried criteria) with important endpoints in older men. DESIGN AND SETTING: Prospective cohort study (the Helsinki Businessmen Study) in Finland. PARTICIPANTS AND MEASUREMENTS: In 1974, clinically healthy men (born 1919-1934, n=1815) of similar socioeconomic status were identified. After a 26-year follow up in 2000 (mean age 73 years), disease prevalence, mobility-disability, and frailty status (80.9% of survivors, n=1125) were appraised using a postal questionnaire including RAND-36. Four criteria were used for definition: 1) >5% weight loss from midlife, or body mass index (BMI) <21 kg/m2; 2) reported physical inactivity; 3) low vitality (RAND-36); 4) physical weakness (RAND-36). Responders with 3-4, 1-2, and zero criteria were classified as frail (n=108), prefrail (n=567), and nonfrail (n=450), respectively. Eight-year mortality was assessed from registers, and in 2007, survivors were re-assessed with questionnaires. RESULTS: Nonfrail as referent and adjusted for age, BMI and smoking, both prefrail (HR 2.26; 95% CI, 1.57-3.26), and frail status (4.09; 95% CI, 2.60-6.44) were significant predictors of mortality. Nonfrailty predicted better survival independently of the frailty components, diseases, and disability, and also predicted faster walking speed and less disability 7 years later. CONCLUSIONS: Frailty, and also prefrailty, as defined using questionnaire data (RAND-36) independently predicted important endpoints in older men. PMID- 22089229 TI - Prevalence of at-risk drinking among older adults and associated sociodemographic and health-related factors. AB - OBJECTIVES: Recognition of alcohol-related health problems in the elderly is challenging. Alcohol use also tends to be a hidden issue. The aim of this study was to examine the prevalence and at-risk drinking patterns in community-dwelling older adults and their associations with socio-demographic and health-related factors. DESIGN: The data were collected with a postal questionnaire from a random sample of 2100 elderly people (>= 65 years) living in the medium-sized city of Espoo, Finland. The response rate was 71.6% from the community-dwelling sample. We defined the amount of at-risk drinking as 1) consuming >7 drinks per week or 2) >5 drinks on a typical drinking day or 3) using >3 drinks several times per week. RESULTS: Of the respondents, 8.2% (N=114) were at-risk drinkers. At-risk drinking was associated with younger age and male sex, higher level of education, good income, living with a spouse, and current smoking. In addition, good functioning was associated with at-risk drinking. Although frequency and quantity of alcohol consumption declined with age, of our respondents nearly one fifth of men aged 71-80 years and one-tenth of men aged 81-90 years could be classified as at-risk drinkers. At-risk drinkers had comorbidities and multiple medications as often as non-risk group. A significantly larger proportion of the at-risk drinking group relative to the non-risk group admitted falling or injuring themselves (5.3% vs. 0.7%) or forgotten to take their medications because of the use of alcohol. CONCLUSIONS: At-risk drinking is prevalent among older adults, particularly among males, despite prevalent comorbidities and multiple medications. At-risk drinking is associated with adverse events such as a tendency for injuries. PMID- 22089230 TI - Frequency of dairy consumption and functional disability in older persons. AB - OBJECTIVES: To examine the association between dairy products consumption frequency and functional disability in older persons. DESIGN: Data were from the 2005 Korea National Health and Nutrition Examination Survey (KNHANES), consisting of 747 (324 men, 423 women) aged 65 years and older living in the community. Frequencies of milk and milk products consumption were obtained using a food frequency questionnaire and functional disability was assessed using the instrumental activities of daily living (IADL) and ADL scales. Logistic regression analyses were conducted to examine the association of dairy consumption frequency with IADL and ADL disability. RESULTS: In men, dietary intake of dairy products was associated with a significantly reduced risk of IADL disability after controlling for known functional disability risk factors and other dietary factors (p for trend, 0.038). Compared with men who consumed dairy products < 1 time/week, those who consumed >= 1 time/day had a reduced risk of IADL disability (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.13-0.91). Meanwhile, milk and milk products consumption was not significantly associated with ADL disability. In women, dairy products consumption was not significantly associated with physical disability. CONCLUSION: Frequent milk and milk products consumption is inversely associated with IADL disability in older men. Further research is needed to ascertain the protective effect of dairy products consumption on functional disability in older persons. PMID- 22089231 TI - Are exploited fish populations stable? PMID- 22089234 TI - What is the appropriate description level for synaptic plasticity? PMID- 22089233 TI - Microbial methane production in oxygenated water column of an oligotrophic lake. AB - The prevailing paradigm in aquatic science is that microbial methanogenesis happens primarily in anoxic environments. Here, we used multiple complementary approaches to show that microbial methane production could and did occur in the well-oxygenated water column of an oligotrophic lake (Lake Stechlin, Germany). Oversaturation of methane was repeatedly recorded in the well-oxygenated upper 10 m of the water column, and the methane maxima coincided with oxygen oversaturation at 6 m. Laboratory incubations of unamended epilimnetic lake water and inoculations of photoautotrophs with a lake-enrichment culture both led to methane production even in the presence of oxygen, and the production was not affected by the addition of inorganic phosphate or methylated compounds. Methane production was also detected by in-lake incubations of lake water, and the highest production rate was 1.8-2.4 nM?h(-1) at 6 m, which could explain 33-44% of the observed ambient methane accumulation in the same month. Temporal and spatial uncoupling between methanogenesis and methanotrophy was supported by field and laboratory measurements, which also helped explain the oversaturation of methane in the upper water column. Potentially methanogenic Archaea were detected in situ in the oxygenated, methane-rich epilimnion, and their attachment to photoautotrophs might allow for anaerobic growth and direct transfer of substrates for methane production. Specific PCR on mRNA of the methyl coenzyme M reductase A gene revealed active methanogenesis. Microbial methane production in oxygenated water represents a hitherto overlooked source of methane and can be important for carbon cycling in the aquatic environments and water to air methane flux. PMID- 22089235 TI - Brassica juncea plant cadmium resistance 1 protein (BjPCR1) facilitates the radial transport of calcium in the root. AB - Calcium (Ca) is an important structural component of plant cell walls and an intracellular messenger in plants and animals. Therefore, plants tightly control the balance of Ca by regulating Ca uptake and its transfer from cell to cell and organ to organ. Here, we propose that Brassica juncea PCR1 (PCR1), a member of the plant cadmium resistance (PCR) protein family in Indian mustard, is a Ca(2+) efflux transporter that is required for the efficient radial transfer of Ca(2+) in the root and is implicated in the translocation of Ca to the shoot. Knock-down lines of BjPCR1 were greatly stunted and translocated less Ca to the shoot than did the corresponding WT. The localization of BjPCR1 to the plasma membrane and the preferential expression of BjPCR1 in the root epidermal cells of WT plants suggest that BjPCR1 antisense plants could not efficiently transfer Ca(2+) from the root epidermis to the cells located inside the root. Protoplasts isolated from BjPCR1 antisense lines had lower Ca(2+) efflux activity than did those of the WT, and membrane vesicles isolated from BjPCR1-expressing yeast exhibited increased Ca(2+) transport activity. Inhibitor studies, together with theoretical considerations, indicate that BjPCR1 exports one Ca(2+) in exchange for three protons. Root hair-specific expression of BjPCR1 in Arabidopsis results in plants that exhibit increased Ca(2+) resistance and translocation. In conclusion, our data support the hypothesis that BjPCR1 is an exporter required for the translocation of Ca(2+) from the root epidermis to the inner cells, and ultimately to the shoot. PMID- 22089232 TI - A biophysically-based neuromorphic model of spike rate- and timing-dependent plasticity. AB - Current advances in neuromorphic engineering have made it possible to emulate complex neuronal ion channel and intracellular ionic dynamics in real time using highly compact and power-efficient complementary metal-oxide-semiconductor (CMOS) analog very-large-scale-integrated circuit technology. Recently, there has been growing interest in the neuromorphic emulation of the spike-timing-dependent plasticity (STDP) Hebbian learning rule by phenomenological modeling using CMOS, memristor or other analog devices. Here, we propose a CMOS circuit implementation of a biophysically grounded neuromorphic (iono-neuromorphic) model of synaptic plasticity that is capable of capturing both the spike rate-dependent plasticity (SRDP, of the Bienenstock-Cooper-Munro or BCM type) and STDP rules. The iono neuromorphic model reproduces bidirectional synaptic changes with NMDA receptor dependent and intracellular calcium-mediated long-term potentiation or long-term depression assuming retrograde endocannabinoid signaling as a second coincidence detector. Changes in excitatory or inhibitory synaptic weights are registered and stored in a nonvolatile and compact digital format analogous to the discrete insertion and removal of AMPA or GABA receptor channels. The versatile Hebbian synapse device is applicable to a variety of neuroprosthesis, brain-machine interface, neurorobotics, neuromimetic computation, machine learning, and neural inspired adaptive control problems. PMID- 22089236 TI - Cooking clue to human dietary diversity. PMID- 22089237 TI - Constitutive coupling of a naturally occurring human alpha1a-adrenergic receptor genetic variant to EGFR transactivation pathway. AB - We previously identified a naturally occurring human SNP, G247R, in the third intracellular loop of the alpha(1a)-adrenergic receptor (alpha(1a)-247R) and demonstrated that constitutive expression of alpha(1a)-247R results in twofold increased cell proliferation compared with WT. In the present study we elucidate molecular mechanisms and signal transduction pathways responsible for increased cell proliferation unique to alpha(1a)-247R, but not alpha(1a)-WT, alpha(1b), or alpha(1d)AR subtypes. We show that elevated levels of matrix metalloproteinase-7 (MMP7) and a disintegrin and metalloproteinase-12 (ADAM12) in alpha(1a)-247R expressing cells are responsible for EGF receptor (EGFR) transactivation, downstream ERK activation, and increased cell proliferation; this pathway is confirmed using MMP, EGFR, and ERK inhibitors. We demonstrate that EGFR transactivation and downstream ERK activation depends on increased shedding of heparin-binding EGF. Finally, we demonstrate that knockdown of MMP7 or beta arrestin1 by shRNAs results in attenuation of proliferation of cells expressing alpha(1a)-247R. Importantly, accelerated cell proliferation triggered by the alpha(1a)-247R is serum- and agonist-independent, providing unique evidence for constitutive active coupling to the beta-arrestin1/MMP/EGFR transactivation pathway by any G protein-coupled receptor. These findings raise the possibility of a previously unexplored mechanism for sympathetically mediated human hypertension triggered by a naturally occurring human genetic variant. PMID- 22089238 TI - Profile of V. Craig Jordan. PMID- 22089239 TI - Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis. AB - The surface expression and regulated endocytosis of kainate (KA) receptors (KARs) plays a critical role in neuronal function. PKC can modulate KAR trafficking, but the sites of action and molecular consequences have not been fully characterized. Small ubiquitin-like modifier (SUMO) modification of the KAR subunit GluK2 mediates agonist-evoked internalization, but how KAR activation leads to GluK2 SUMOylation is unclear. Here we show that KA stimulation causes rapid phosphorylation of GluK2 by PKC, and that PKC activation increases GluK2 SUMOylation both in vitro and in neurons. The intracellular C-terminal domain of GluK2 contains two predicted PKC phosphorylation sites, S846 and S868, both of which are phosphorylated in response to KA. Phosphomimetic mutagenesis of S868 increased GluK2 SUMOylation, and mutation of S868 to a nonphosphorylatable alanine prevented KA-induced SUMOylation and endocytosis in neurons. Infusion of SUMO-1 dramatically reduced KAR-mediated currents in HEK293 cells expressing WT GluK2 or nonphosphorylatable S846A mutant, but had no effect on currents mediated by the S868A mutant. These data demonstrate that agonist activation of GluK2 promotes PKC-dependent phosphorylation of S846 and S868, but that only S868 phosphorylation is required to enhance GluK2 SUMOylation and promote endocytosis. Thus, direct phosphorylation by PKC and GluK2 SUMOylation are intimately linked in regulating the surface expression and function of GluK2-containing KARs. PMID- 22089240 TI - Delayed cord clamping and improved infant outcomes. PMID- 22089241 TI - Is it unethical for doctors to encourage healthy adults to donate a kidney to a stranger? No. PMID- 22089243 TI - Is it unethical for doctors to encourage healthy adults to donate a kidney to a stranger? Yes. PMID- 22089242 TI - Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial. AB - OBJECTIVE: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting. DESIGN: Randomised controlled trial. SETTING: Swedish county hospital. PARTICIPANTS: 400 full term infants born after a low risk pregnancy. INTERVENTION: Infants were randomised to delayed umbilical cord clamping (>= 180 seconds after delivery) or early clamping (<= 10 seconds after delivery). MAIN OUTCOME MEASURES: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy. RESULTS: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 MUg/L v 81 MUg/L, P < 0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P = 0.01, relative risk reduction 0.90; number needed to treat = 20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P = 0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy. CONCLUSIONS: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia. Trial registration Clinical Trials NCT01245296. PMID- 22089244 TI - Acquired Omenn-like syndrome, a novel posttransplant autoaggression syndrome reversed by rapamycin. AB - Graft-versus-host disease is uncommon in autologous hematopoietic cell transplantation (HCT) and is typically brief and mild. We report unusual, protracted, and severe Omenn syndrome-like autoaggression following autologous HCT. We identified a profound FOXP3(+) regulatory T cell defect that coincided with hyperinflammatory T cell responses which were reversible with rapamycin in vitro. PMID- 22089245 TI - Anthrax vaccine antigen-adjuvant formulations completely protect New Zealand white rabbits against challenge with Bacillus anthracis Ames strain spores. AB - In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-water emulsion, PA displayed on bacteriophage T4 by the intramuscular route, and PA mixed with Escherichia coli heat-labile enterotoxin administered by the needle-free transcutaneous route. Three of the vaccine formulations administered by the intramuscular or the transcutaneous route as a three-dose regimen induced 100% protection in the rabbit model. One of the formulations, liposomal PA, also induced significantly higher lethal toxin neutralizing antibodies than PA-Alhydrogel. Even 5 months after the second immunization of a two-dose regimen, rabbits vaccinated with liposomal PA were 100% protected from lethal challenge with Ames strain spores. In summary, the needle-free skin delivery and liposomal formulation that were found to be effective in two different animal model systems appear to be promising candidates for next generation anthrax vaccine development. PMID- 22089246 TI - Optimized adenovirus-antibody complexes stimulate strong cellular and humoral immune responses against an encoded antigen in naive mice and those with preexisting immunity. AB - The immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity. In vitro and in vivo assays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 * 10(11) adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND(50)) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND(50) formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P = 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 +/- 5.2% proliferation versus 7.7 +/- 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND(50)) of antibody did not improve cellular and humoral responses in naive animals, they did promote strong cellular (0.005 ND(50)) and humoral (0.0005 ND(50)) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus based vaccines in naive individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus. PMID- 22089247 TI - Prophylactic and therapeutic vaccination using dendritic cells primed with peptide 10 derived from the 43-kilodalton glycoprotein of Paracoccidioides brasiliensis. AB - Vaccination with peptide 10 (P10), derived from the Paracoccidioides brasiliensis glycoprotein 43 (gp43), induces a Th1 response that protects mice in an intratracheal P. brasiliensis infection model. Combining P10 with complete Freund's adjuvant (CFA) or other adjuvants further increases the peptide's antifungal effect. Since dendritic cells (DCs) are up to 1,000-fold more efficient at activating T cells than CFA, we examined the impact of P10-primed bone-marrow-derived DC vaccination in mice. Splenocytes from mice immunized with P10 were stimulated in vitro with P10 or P10-primed DCs. T cell proliferation was significantly increased in the presence of P10-primed DCs compared to the peptide. The protective efficacy of P10-primed DCs was studied in an intratracheal P. brasiliensis model in BALB/c mice. Administration of P10-primed DCs prior to (via subcutaneous vaccination) or weeks after (via either subcutaneous or intravenous injection) P. brasiliensis infection decreased pulmonary damage and significantly reduced fungal burdens. The protective response mediated by the injection of primed DCs was characterized mainly by an increased production of gamma interferon (IFN-gamma) and interleukin 12 (IL-12) and a reduction in IL-10 and IL-4 compared to those of infected mice that received saline or unprimed DCs. Hence, our data demonstrate the potential of P10 primed DCs as a vaccine capable of both the rapid protection against the development of serious paracoccidioidomycosis or the treatment of established P. brasiliensis disease. PMID- 22089248 TI - Poly-gamma-glutamic acid nanoparticles and aluminum adjuvant used as an adjuvant with a single dose of Japanese encephalitis virus-like particles provide effective protection from Japanese encephalitis virus. AB - To maintain immunity against Japanese encephalitis virus (JEV), a formalin inactivated Japanese encephalitis (JE) vaccine should be administered several times. The repeated vaccination is not helpful in the case of a sudden outbreak of JEV or when urgent travel to a high-JEV-risk region is required; however, there are few single-injection JE vaccine options. In the present study, we investigated the efficacy of a single dose of a new effective JE virus-like particle preparation containing the JE envelope protein (JE-VLP). Although single administration with JE-VLP protected less than 50% of mice against lethal JEV infection, adding poly(gamma-glutamic acid) nanoparticles (gamma-PGA-NPs) or aluminum adjuvant (alum) to JE-VLP significantly protected more than 90% of the mice. A single injection of JE-VLP with either gamma-PGA-NPs or alum induced a significantly greater anti-JEV neutralizing antibody titer than JE-VLP alone. The enhanced titers were maintained for more than 6 months, resulting in long-lasting protection of 90% of the immunized mice. Although the vaccine design needs further modification to reach 100% protection, a single dose of JE-VLP with gamma PGA-NPs may be a useful step in developing a next-generation vaccine to stop a JE outbreak or to immunize travelers or military personnel. PMID- 22089249 TI - Influence of dietary sodium modulation on electrocardiographic voltage criteria for left ventricular hypertrophy in normotensive individuals. AB - OBJECTIVE: Dietary sodium intake and left ventricular hypertrophy (LVH) on electrocardiogram (ECG) are both independent determinants of cardiovascular risk. Prior studies demonstrated that acute dietary sodium modulation significantly altered LVH-specific ECG voltage in hypertensive individuals, thus modifying cardiovascular risk prediction; but whether this phenomenon exists in normotensive individuals is not known. We evaluated the influence of dietary sodium intake on ECG voltage and ECG criteria for LVH in normotensive individuals. METHODS: Retrospective evaluation of ECGs of healthy normotensive individuals (n = 39) who were prospectively randomized to a dietary study protocol of 1 week of high-sodium diet (>200 mmol of sodium per day) and 1 week of low-sodium diet (<10 mmol/d) was conducted. Electrocardiogram voltage amplitudes and biochemical assessments were performed at the end of each dietary intervention. RESULTS: As expected, blood pressure declined and measures of circulating renin-angiotensin-aldosterone system activity rose significantly with low-sodium diet. No significant changes in specific LVH voltage criteria or overall precordial or limb lead ECG voltage amplitudes were detected between diets. CONCLUSION: Although immediate dietary sodium modulation has been shown to significantly alter LVH-specific ECG voltage and the detection of LVH in hypertensive individuals, dietary sodium intake did not influence ECG voltage in normotensive individuals. Healthy normotensive individuals may exhibit adaptive measures that dampen ECG voltage fluctuations in response to dietary sodium modulation. More specific cardiac imaging studies may provide additional insight into this observation and the influence of dietary sodium in cardiac health. PMID- 22089250 TI - Properties and structure of interfacial layers formed by hydrophilic silica dispersions and palmitic acid. AB - The properties and structure of different types of interfacial layers obtained from aqueous dispersions of nanometric silica and palmitic acid (PA) have been studied and characterized by different diagnostics and measurements. The investigations concern PA monolayers spread on the silica dispersions, dispersions in contact with PA solutions in oil and silica dispersions containing PA, aiming at elucidating the role of the PA interaction with the particles and investigating the surface-activity of the originated silica-PA complexes. Drop shape tensiometry was utilized to measure the dynamic surface and interfacial tension while a Langmuir trough apparatus was used to obtain compression isotherms of the spread PA layers and to measure the dilational viscoelasticity according to the oscillating barrier method. Brewster angle microscopy and ellipsometry were utilized to investigate the lateral and vertical structure of the interfacial layers. From this multifold approach emerges a complex picture of the features of these interfacial layers that can be rationalized on the basis of the adsorption of PA on the particle surface. The results evidence a threshold in PA adsorption above which particles change from hydrophilic to partially hydrophobic, promoting their incorporation into the interfacial layer. PMID- 22089252 TI - Presence of minimal change esophagitis closely correlates with pathological conditions in the stomach. AB - INTRODUCTION: It is suggested that minimal change (grade M) esophagitis is a spectrum of gastric acid reflux disease. We evaluated the clinical significance of grade M esophagitis, including its subtypes (reddish change: MR and whitish change: MW), especially with attempt to pathological conditions in the stomach that relates to gastric acid secretion. MATERIALS AND METHODS: Using 241 subjects undergoing esophagogastroduodenoscopy for various indications, we investigated the association between grade M esophagitis with histological and serological severity of gastritis and endoscopic degree of atrophy. We also examined its association with ulcer diseases and various symptoms. RESULTS: When grade M cases were divided into MR and MW, all MR cases had MW in considerable degrees. Dyspeptic symptoms were more likely to be associated with H. pylori negative grade M cases, while presence of duodenal ulcer and its scar were associated with Helicobacter pylori-positive grade M cases. In all subjects, histological parameters, especially in the corpus, were lower in grade M cases compared to normal appearance. In grade M cases, degree of acute and chronic inflammation, and atrophy in corpus were lowest in cases that have grade MR. Grade M cases were also associated with higher pepsinogen I/II ratio and lower endoscopic atrophy. CONCLUSIONS: Pathological conditions of the stomach relate to higher gastric acid secretion correlates with grade M esophagitis. In grade M cases, appearance of MR may reflect higher gastric acid secretion or severe acid reflux than cases that have grade MW only. PMID- 22089251 TI - Understanding biomolecular motion, recognition, and allostery by use of conformational ensembles. AB - We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomolecules and illustrate their application with relevant examples from the literature. We show how, for binding, conformational ensembles provide a way of distinguishing the competing models of induced fit and conformational selection. For allostery we review the classic models and show how conformational ensembles can play a role in unravelling the intricate pathways of communication that enable allostery to occur. Finally, we discuss the limitations of conformational ensembles and highlight some potential applications for the future. PMID- 22089253 TI - Abdominal mass, anemia, diabetes mellitus, and necrolytic migratory erythema. PMID- 22089254 TI - Durability of infliximab dose intensification in Crohn's disease. AB - BACKGROUND: Dose intensification is a common approach to treat Crohn's disease (CD) patients who lose response to infliximab maintenance therapy. Few studies have reported upon its long-term efficacy or predictors of response. AIM: The goal of this study is to investigate durability and predictors of response to dose intensification-including method of dose intensification, combination immunomodulator therapy, and premedication with intravenous hydrocortisone. METHODS: We performed a retrospective study of dose-intensified CD patients at our institution. Dose intensification was defined as an increase in dose from 5 to 10 mg/kg, an increase in frequency of infusions from every 8 weeks to every 6 weeks or less, or both an increase in dose and frequency. RESULTS: Thirty CD patients (mean age, 39.9 years) met study criteria and underwent dose intensification. Ten (33.3%) patients remained on dose intensification at the end of our study or returned to their former infliximab dose or schedule (median follow-up, 41 months). Fourteen patients (46.7%) eventually lost response to dose intensification, but dose intensification extended infliximab therapy by a median duration of 9 months. Six patients (20%) didn't respond to dose intensification. Neither method of dose intensification, combination immunomodulator therapy, nor premedication with intravenous hydrocortisone predicted initial or durable response to dose intensification. However, analysis of predictors was limited by the small sample size of our study. CONCLUSIONS: The majority of CD patients respond to dose intensification, and a substantial portion will experience durable response such that infliximab therapy is successfully extended by one or more years. PMID- 22089255 TI - Thalidomide treatment in cirrhotic patients with severe anemia secondary to vascular malformations. PMID- 22089256 TI - Angiotensin-(1-7) inhibits the migration and invasion of A549 human lung adenocarcinoma cells through inactivation of the PI3K/Akt and MAPK signaling pathways. AB - The local renin-angiotensin system (RAS) is one of the crucial components in the tumor microenvironment. Recent evidence suggests that the local RAS plays an important role in tumor metabolism, survival, angiogenesis and invasion processes. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous peptide of the RAS with vasodilator and anti-proliferative properties. Previous studies have demonstrated that Ang-(1-7) inhibits both the growth of human lung cancer cells in vitro and tumor angiogenesis in vivo through activation of the MAS receptor. This study investigated the anti-metastatic effect of Ang-(1-7) in A549 human lung adenocarcinoma cells in vitro. We found that Ang-(1-7) reduced the cell migratory and invasive abilities by reducing the expression and activity of MMP-2 and MMP 9. Furthermore, we demonstrated that the anti-migration and anti-invasion effect of Ang-(1-7) was mediated through inactivation of the PI3K/Akt, P38 and JNK signal pathways. Our results suggest that Ang-(1-7) may have therapeutic potential against advanced lung carcinoma as a new agent. PMID- 22089257 TI - [The medical management of high risk individuals. Experiences with persons exposed to chronic internal irradiation]. AB - The medical management and counseling of persons at high risk due to exposure to chemicals or radiation or due to personal disposition, present an additional challenge for physicians and especially radiologists involved. This article is based on own experiences with patients who had been exposed to Thorotrast. They had been injected with the contrast medium Thorotrast, which was in use world wide until around 1950. Thorotrast caused a chronic alpha irradiation mainly of the liver (up to 0.4 Gy/a), spleen (1.2 Gy/a) and bone marrow (0.1 Gy/a). For the Thorotrast patients and their physicians the most worrying problem was the risk of primary malignant liver tumors which occurred in more than 20% of the exposed persons, i.e. 100 times more frequently than in a non-exposed control group. The medical and especially radiological experiences with the management of these patients summarize a general aspect of the problem and can be referred to when managing other high risk groups. PMID- 22089258 TI - Short- and long-term outcomes following percutaneous cholecystostomy for acute cholecystitis in high-risk patients. AB - BACKGROUND: Percutaneous cholecystostomy is a less invasive method to treat acute cholecystitis in patients who are critically ill or have serious medical comorbidities precluding the use of general anesthesia. It remains controversial whether interval cholecystectomy is warranted. The objectives of the study were to determine the success rate and complications of percutaneous cholecystostomy and the proportion of patients without recurrent attacks in whom interval cholecystectomy was not needed. METHODS: This was a retrospective review to determine the outcomes after percutaneous cholecystostomy for acute calculous cholecystitis between 1995 and 2007. Administrative data were used to better capture recurrent symptoms requiring treatment. RESULTS: Sixty-eight patients with a mean age of 74 years were identified. Sixty-seven (98.5%) underwent successful insertion of the cholecystostomy tubes. Eleven patients suffered tube related complications, including tube dislodgment (9), tube blockage (1), and bleeding that was controlled with conservative management (1). The initial episode of cholecystitis was treated successfully in 58 patients (85%). The overall in-hospital and 30-day mortality were both 15% (10 patients). A total of 7 patients (10%) underwent cholecystectomy while still in hospital. There were 39 patients at risk for recurrent disease who survived the initial episode and did not receive an interval cholecystectomy. Of these 39 patients, 16 (41%) suffered recurrent gallbladder-related disease. CONCLUSIONS: Percutaneous cholecystostomy is an alternative to cholecystectomy in patients with acute calculous cholecystitis who are at high risk for surgical mortality and morbidity. It appears to have a low complication rate and good clinical success. Because a significant number of patients suffer recurrent attacks, elective cholecystectomy should be considered routinely. Unfortunately, firm criteria for selecting percutaneous cholecystostomy over cholecystectomy are lacking, and the surgeon's clinical judgment is critically important. PMID- 22089259 TI - The prognostic impact of positive lymph nodes in stages T1 to T3 incidental gallbladder carcinoma: results of the German Registry. AB - BACKGROUND: In the literature, the 5 year survival rates for incidental gallbladder carcinoma (IGBC) show large variations in the different T-stages because the lymph node status often is not addressed. Most early-stage carcinomas are identified by laparoscopy as IGBC, and radical re-resection is needed. Staging is impossible without lymph node dissection, so comparison between various survival rates is impossible. This study aimed to determine the influence of lymph node status on the survival of patients with stages T1 to T3 IGBC. METHODS: For data analysis, the German Registry was used. RESULTS: In this study, 709 patients with IGBC were analyzed. The re-resected nodal-negative patients had a significant survival advantage over the re-resected nodal-positive patients. The 5 year survival rate for the patients with nodal-negative re-resected T1 carcinomas was 75%. The re-resected T2 and T3 nodal-negative patients had significantly better survival than the corresponding nodal-positive patients. The influence that the radicalness of the different liver resection techniques had on these results was excluded. 53 patients without radical resection had a known nodal-positive status. Nodal-positive patients with radical re-resection always show a better survival rate than nodal-positive patients without radical re resection, stage for stage. CONCLUSIONS: Nodal-positive status is a significant negative prognostic factor in T1 to T3 IGBC. Patients with radical re-resection show a better survival rate than those without it. Lymph node dissection is to be highly recommended up to stage T1b. In the case of T2 carcinomas, lymph node dissection of the hepatoduodenal ligament seems to be the minimum volume of lymph node dissection required, but more radical procedures could be beneficial for tumors infiltrating the serosa or beyond. PMID- 22089260 TI - A 20 mSv dose limit for the eye: sense or no sense? PMID- 22089261 TI - Male infertility in Northeast China: a cytogenetic study of 135 patients with non obstructive azoospermia and severe oligozoospermia. AB - PURPOSES: To detect the frequency and types of chromosomal anomalies with non obstructive azoospermia and severe oligozoospermia in Northeast China, and to compare the frequencies with other regions of China and the world. To investigate the general characteristics of this population. METHODS: Eighty-one men with non obstructive azoospermia and 54 men with severe oligozoospermia were recruited. Karyotype analyses were performed on peripheral blood lymphocytes using standard G-banding. Measurements of follicle-stimulating hormone, testosterone, prolactin, and inhibin B were obtained. RESULTS: The frequency of chromosomal anomalies for patients with non-obstructive azoospermia (17.28%) was comparable with studies from Europe, Africa, Asia, and other regions of China. However, the frequency for patients with severe oligozoospermia (9.26%) was slightly higher than reported from other Asian countries. The infertile men were more likely than the fertile to smoke and consume alcohol, and to have significantly lower levels of inhibin B. CONCLUSIONS: For infertile men in Northeast China, chromosome analysis is a necessary part of routine genetic testing, and the contributing effects of high smoking and alcohol consumption rates of this population should be discussed during genetic counseling. PMID- 22089262 TI - Aqueous extract of Azadirachta indica (neem) leaf induces generation of reactive oxygen species and mitochondria-mediated apoptosis in rat oocytes. AB - OBJECTIVE: Present study was aimed to determine whether aqueous neem leaf extract (NLE) induces generation of reactive oxygen species (ROS) and apoptosis through mitochondria-mediated pathway in rat oocytes. DESIGN: A controlled prospective study. SETTING: Laboratory research setting at Department of Zoology of Banaras Hindu University. ANIMAL(S): Forty eight sexually immature female rats that were 20-30 days of age. INTERVENTION(S): Sexually immature female rats were fed palatable dose of NLE (10 mg/g dry feed palate) for 10 days and then subjected to superovulation induction protocol. Thereafter, rats were euthanized, ovulated cumulus oocyte complexes were collected from oviduct and oocytes were denuded. MAIN OUTCOME MEASURE(S): Rate of morphological apoptotic changes, measurement of hydrogen peroxide, nitric oxide and cytochrome c concentrations, caspase-9, caspases-3 activities and DNA fragmentation in oocytes. RESULTS: In vivo NLE treatment induced morphological apoptotic changes were associated with increased hydrogen peroxide, nitric oxide and cytochrome c concentrations, caspase-9, caspase-3 activities and DNA fragmentation in oocyte. CONCLUSION: NLE induces generation of ROS that leads to oocytes apoptosis through mitochondria-mediated pathway. PMID- 22089263 TI - Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation. AB - PURPOSE: The association of cytochrome P450 aromatase gene CYP19(TTTA) ( n ) polymorphism with ovarian response to FSH stimulation was explored. METHODS: Three hundred women undergoing medically assisted reproduction and 300 women with at least one spontaneous pregnancy participated in the study. CYP19(TTTA) ( n ) polymorphism was genotyped, while serum hormones were determined. During oocyte retrieval, the follicular size, the follicle and oocyte numbers were recorded. RESULTS: Six CYP19(TTTA) ( n ) alleles with 7 to 12 repeats were revealed. Women homozygous for long CYP19(TTTA) ( n ) alleles presented with lower serum FSH levels at the third day of the menstrual cycle (p < 0.001) and higher large follicle numbers (p < 0.01), compared to women homozygous for short CYP19(TTTA) ( n ) alleles. The CYP19(TTTA) ( 7 ) allele was associated with higher serum FSH levels (p < 0.003), with lower total follicle (p < 0.02) and large follicle numbers (p < 0.03), while CYP19(TTTA) ( 7 ) allele-carriers presented more frequently with small follicles than CYP19(TTTA) ( 7 ) allele-non carriers (p < 0.01). CONCLUSIONS: CYP19 genetic variants were associated with ovarian reserve and response to standard gonadotrophin stimulation of women undergoing in vitro fertilization. PMID- 22089264 TI - Maturation outcomes are improved following Cryoleaf vitrification of immature human oocytes when compared to choline-based slow-freezing. AB - PURPOSE: The cryopreservation of immature oocytes permits oocyte banking for patients at risk of losing their fertility. However, the optimum protocol for such fertility preservation remains uncertain. METHODS: The present study investigated the survival, maturation, cytoskeletal and chromosome organization of sibling immature oocytes leftover from controlled ovarian stimulation cycles, that were either slow-frozen (with choline-substitution) or vitrified. A comparison group included oocytes that were never cryopreserved. RESULTS: Among the three groups, comparable rates were observed for both survival (67-70%) and polar body extrusion (59-79%). Significantly more oocytes underwent spontaneous activation after IVM following slow-freezing compared with either vitrification or no cryopreservation. Likewise, the incidence of spindle abnormalities was greatest in the slow-frozen group, with no differences in spindle morphometrics or chromosome organization. CONCLUSIONS: While the overall incidence of mature oocytes with normal bipolar spindles from warmed immature oocytes was low, the yield using Cryoleaf vitrification was slightly superior to choline-based slow freezing. PMID- 22089265 TI - Severe ovarian hyperstimulation syndrome after letrozole-gonadotropin stimulation: a case report. PMID- 22089266 TI - A novel metric to assess the clinical utility of a drug in the presence of efficacy and dropout information. AB - The fact that there are high dropout rates in clinical trials of antipsychotic medications raises critical questions regarding the most appropriate method of designing new trials, analyzing efficacy data, and evaluating the clinical utility (CU) of novel treatments. In this article, we consider the use of a model based approach to define an integrated CU criterion for better characterizing the clinical response to a treatment, for optimizing proof-of-concept trials, and for providing differentiating criteria for novel medications when complete information is not available. PMID- 22089267 TI - High-dose ibuprofen for patent ductus arteriosus in extremely preterm infants: a randomized controlled study. AB - Our aim was to assess the hypothesis that a high-dose regimen of ibuprofen is more effective than the standard-dose regimen in closing patent ductus arteriosus (PDA) without increasing adverse effects. Infants of gestational age <29 weeks, with respiratory distress syndrome (RDS) and echocardiographic evidence of significant PDA at 12-24 h of life, were randomized to receive a standard (10-5-5 mg/kg/day) or high-dose (20-10-10 mg/kg/day) course of ibuprofen. We studied 70 infants, 35 of whom received the standard dose of ibuprofen and the other 35 the high dose. Of the infants treated with the standard-dose regimen, 37% had persistent PDA as compared with 14% of those treated with the high-dose regimen (P = 0.03). No differences in the occurrence of adverse effects were observed between the two groups. The high-dose ibuprofen regimen is more effective than the standard-dose regimen in closing PDA in preterm infants <29 weeks of gestation without increasing the adverse effect rate. PMID- 22089268 TI - Stem cell senescence and regenerative paradigms. AB - The term "cellular senescence" denotes a cellular response to several stressors that results in irreversible growth arrest, alterations of the gene expression profile, epigenetic modifications, and an altered secretome, all of which eventually impair the reparative properties of primitive cells, adding a layer of complexity to the field of regenerative medicine. The purpose of this review is to illustrate how cellular senescence could affect tissue repair and to propose interventions that aim at interfering with it. PMID- 22089269 TI - Magnetic field driving gradient effects on the microstructure in amorphous nanocrystalline cobalt alloy ribbons. AB - Field effects on the early crystallization of Co-rich amorphous ribbons (Co(68.15)Fe(4.35)Si(12.5)B(15), atomic%) performed at 450 degrees C for 30 minutes in an applied 10 Oe longitudinal or transverse external magnetic field are investigated by comparing with the as-spun and annealed samples in zero applied magnetic field. Results indicate that the crystallization on the surface skin of the ribbon differs from that of the middle section due to the combined effects from the field direction and the defects or stress characteristics across the ribbons. In particular, the ribbons annealed under a transverse field exhibit an extremely distinct graded microstructure across the ribbon, which features amorphous-phased skin layers (top and bottom) of about 4-5 MUm thickness and a middle amorphous-nanocrystalline composite layer about 10-12 MUm thick, with the nanograins of 434 +/- 99 nm dispersing in the amorphous matrix. PMID- 22089270 TI - A critical pathway for the frail elderly cardiac patient. AB - BACKGROUND: The medical community needs to better respond to the predictable complexities associated with admission of frail and elderly cardiac patients who may need specific attention and care programs. The nurse practitioner can play an important role to continue and coordinate nursing and medical care. We propose a new critical pathway designed to improve cardiac and nursing care for frail elderly cardiac patients admitted with heart failure or atrial fibrillation. METHOD: The critical pathway is developed by the nurse practitioner who will act as a pathway coordinator and take care of the medical care of these patients in a teaching hospital setting. This critical pathway is applied to all patients aged >75 years who are admitted for heart failure or atrial fibrillation. RESULTS: The pathway implementation identified 5 important socio-medical parameters that may account for a delayed length of stay, even in patients without a complicated medical situation: delirium and fall prevention, nutritional awareness, fluid restriction efforts, and information optimization of patients and spouses. CONCLUSIONS: We developed a critical care pathway for the frail elderly patients who are admitted for heart failure or atrial fibrillation. In doing so, we have been able to change the medical and social management of these patients at a general cardiology ward in a teaching hospital. PMID- 22089271 TI - Take heart: a one-on-one peer-based strategy to improve acute coronary syndrome patient care. AB - Acute coronary syndromes (ACS) result in more than 1 million hospitalizations each year in the United States and are a leading cause of morbidity and mortality. Despite evidence-based treatment guidelines and advances in therapeutic strategies, the need for well-educated practitioners to provide quality patient care is still evident. As such, continuing medical education (CME) and consultation with recognized experts are valuable tools that can enhance clinical knowledge and lead to improvements in best practices. In a CME platform, collaborative dialogue with nationally recognized opinion leaders within the field of ACS enabled 111 clinician participants to develop strategies for personal practice improvement. Faculty experts addressed specific challenging clinical questions posed by participants regarding 1 of 4 preselected topics related to the care of patients with ACS. After a 3-month period, 94% of participants reported that their strategies for practice improvement had affected patient care. Participants also rated the utility of national guidelines in their practices higher following participation in the activity and demonstrated improved clinical knowledge. As a result of this activity, participants were able to solve self-identified issues in clinical practice as well as improve their understanding of current clinical practice guidelines. Adherence to guideline recommended care was associated with improvements in patient outcomes, and participant feedback suggests that this was an effective type of CME platform that resulted in positive changes in patient care. Furthermore, considerable interest exists for the application of this model in other therapeutic areas. PMID- 22089272 TI - Pathways in heart failure disease management across socioeconomic spectra. AB - Caring for heart failure patients with a low socioeconomic status presents a unique set of challenges for health care providers. Heart failure disease management programs can integrate the use of teaching DVDs to overcome deficiencies in health literacy and take advantage of the Wal-Mart/Target $4 dollar medication program to provide life-saving medical therapy. In addition, open discussions with the patient and family regarding the costs of medications and the reality of what they can afford to pay monthly on a long term basis can guide the physician to prescribing medications by prioritizing use with a focus on evidence-based data for the medications with the highest mortality reduction. Finally, connecting inpatient visits to outpatient visits through the use of electronic medical records systems can facilitate avoidance of unnecessary repeat lab and diagnostic testing. PMID- 22089273 TI - Carotid intima-media thickness determined vascular age and the Framingham Risk Score. AB - We examined carotid intima-media thickness (CIMT)-determined vascular age on the Framingham Risk Score (FRS) and the Framingham Heart Age in patients of diverse ethnic origin without a history of diabetes or established cardiovascular disease. In this cross-sectional study, 2291 men and women had CIMT obtained by high resolution B-mode ultrasound in a routine examination between August 1, 2000 and October 1, 2001. We randomly split the population into a training subset (n = 1114) and an analysis subset (n = 1177) using the training subset to regress the average CIMT for each individual on chronologic age. We compared the FRS using CIMT-determined vascular age versus chronologic age in the analysis subset. On average, CIMT-determined vascular age was less than chronologic age, which was less than FRS-heart age in all gender and ethnic groups. For estimated 10-year cardiovascular-disease risk among non-Hispanic whites, only 45.5% of male and 55.6% of female patients were concordant for both measures, and simple Kappa values were low (0.28 for males, 0.32 for females). Among non-Hispanic whites, 40.7% of males and 32.1% of females had greater risk using chronologic age rather than when using CIMT-determined vascular age. Conversely, 13.8% of males and 12.3% of females had a greater risk using CIMT-determined vascular age rather than when using chronologic age. A similar pattern was noted in the other ethnic groups. Our results suggest that CIMT may be very useful in improving risk discrimination in the FRS, and that substituting CIMT-determined vascular age may improve individual cardiovascular risk prediction. PMID- 22089274 TI - Role of N-terminal pro-brain natriuretic peptide in ST-segment elevation myocardial infarction: experience from a tertiary centre in India. AB - BACKGROUND: Role of biomarkers in ST-segment elevation myocardial infarction (STEMI) is paramount, as they aid in diagnosis and gauge prognosis of the disease. In this project, we sought to study the short-term outcome and clinical associates of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the setting of STEMI at a tertiary center in India. METHODS: In all, 173 STEMI patients (mean age: 57 +/- 12 years, 38 women) had their NT-proBNP assayed in addition to troponins and high-sensitive C-reactive protein. Subjects were divided according to NT-proBNP levels into 2 groups: group 1 (NT-proBNP <=100 pg/mL) and group 2 (NT-proBNP >100 pg/mL). RESULTS: NT-proBNP values (pg/mL) were elevated in group 2 (group 1: 61.7 +/- 6.2; group 2: 1006.5 +/- 990.6, P < 0.0001). Significantly greater number of females had elevated NT-proBNP (P < 0.05) that could be predicted by the duration of chest pain related to STEMI (area under the curve: 0.72), and age at presentation (area under the curve: 0.66). Multiple regression analysis showed a strong inverse association between NT-proBNP and left ventricular ejection fraction and a strong positive association between the peptide and high-sensitive C-reactive protein. A significant positive association was also noted between NT-proBNP and troponin I (all P < 0.05, Global R = 0.47). Diabetes mellitus and/or hypertension, and infarction localization showed no effect on NT-proBNP levels along with death, primary coronary intervention related bleeding, and arrhythmias, (chi, P = ns). CONCLUSIONS: The data suggest that women are more likely to have increased NT-proBNP while presenting with STEMI. Duration of chest pain and age at presentation are the best predictors of elevated NT-proBNP, though without much bearing on short-term morbidity and mortality. PMID- 22089275 TI - Influence of bedside blood insulin measurement on acute coronary syndrome pathways. AB - BACKGROUND: The aim of the study was to evaluate the influence of blood insulin measurements on acute coronary syndrome (ACS) pathways. METHODS: All patients admitted to the emergency department within 12 months for acute, retrosternal, constrictive chest pain lasting for more than 30 minutes; cardiogenic pulmonary edema; electrocardiogram ST changes; and echographic alterations were included. The study parameters were clinical (age, sex, blood pressure, presence of pulmonary rales and gallop), including classic laboratory tests associated with troponin T, blood insulin levels, and hemoglobin A1C, and echographic values. These were taken on admission and throughout hospital stay. All patients underwent a coronary angiography for ACS diagnosis confirmation as well as treatment intention. RESULTS: Sixty patients were included in the study. Abnormal blood insulin levels were present on admission in 47% of the population. Blood insulin level was significantly correlated to thrombolysis in myocardial infarction coronary perfusion score (Spearman Rank, 0.55, P < 0.0001). Abnormal insulinemia was normalized with reperfusion. Insulin was administered essentially to the 16 patients with hypoinsulinemia. Patients with hypoinsulinemia seem to have the most severe coronary lesions and highest Killip score. CONCLUSIONS: In ACS, insulin levels are altered in half of the patients. After the investigators noted its tight correlation with the thrombolysis in myocardial infarction coronary flow score, its determination could be important in ACS for triggering emergency coronary angiography for percutaneous coronary intervention. This could modify the critical pathways of ACS patients in the emergency department. PMID- 22089276 TI - Use of endothelial progenitor capture cell stent during percutaneous treatment of coronary bifurcations: a prospective angiographic registry. AB - BACKGROUND: The treatment of bifurcation lesions remains a challenge with poor immediate results and higher restenosis rate than in nonbifurcated lesions. Drug eluting stents improve the outcome after coronary stenting, but are associated with a small but statistically significant increase in late and very late stent thrombosis. Thus, aim of the present study was to evaluate the angiographic and clinical results of a new type of stent (coated with murine monoclonal antihuman CD34 antibodies designed to attract circulating endothelial progenitor cells to rapidly establish a functional endothelial layer and promote healing stent implantation) in a cohort of consecutive patients with coronary bifurcation lesions. METHODS AND RESULTS: Between December 2007 and July 2008, a total of 43 consecutive patients were enrolled and 47 consecutive bifurcation lesions were treated with endothelial progenitor capture cell stents. The angiographic end points binary restenosis rate inside the stent (within 5 mm of the stent edges or in the segments treated with balloon angioplasty) was 5% (2.1% in the main branch and 10.5% in the side branch). No stent thrombosis was observed. Clinical follow up was completed in all patients at mean time of 34.5 days after percutaneous coronary interventions by clinical evaluation and 12.3 months with a telephone contact. Angina at rest was present in 3 patients (7.9%). No in-hospital, 30 days, or 12-months major adverse cardiac events (death, myocardial infarction, and repeat revascularization coronary artery bypass graft or percutaneous coronary angioplasty) were reported. CONCLUSIONS: The use of endothelial progenitor capture cell in the setting of coronary bifurcation appears to be feasible and safe with no incidence of late stent thrombosis and a very low rate of repeated revascularization. PMID- 22089277 TI - Society of Chest Pain Centers heart attack care in the United States: a commentary by Raymond D. Bahr, MD, FACC. PMID- 22089278 TI - Society of Chest Pain Centers offers system discount for hospitals seeking Cycle IV Chest Pain Center accreditation. PMID- 22089279 TI - Society of Chest Pain Centers meeting the needs of critical access hospitals. PMID- 22089280 TI - Pulmonary rehabilitation in the management of COPD: more than one way to skin a cat. PMID- 22089281 TI - Tendinopathy of the tendon of the long head of the biceps. AB - Pathologies of tendon of the long head of the biceps (LHB) are an important cause of shoulder pain. They include tendinopathy, rupture, superior labrum anterior and posterior lesions, pulley tears, and tendon instability. Conservative management of symptomatic LHB tendinopathy is commonly accepted as the first-line treatment. It consists of rest, nonsteroidal anti-inflammatory drugs, corticosteroid injections, and physical therapy. Biceps tenotomy and tenodesis are the most common surgical procedures to manage both isolated LHB pathology and biceps-glenoid complex tears combined with rotator cuff tears. However, controversy persists about the superiority of one of them because there is no evidence of significant differences in functional scores or patient satisfaction between the 2 techniques. This article provides an overview on biomechanical function of the LHB and current strategies for treatment of LHB disorders. PMID- 22089282 TI - Arthroscopic management of subscapularis tears. AB - Tears of the subscapularis were previously believed to be rare, but are now recognized to be very common. As maintenance of the subscapularis footprint is integral to normal biomechanical function of the shoulder it is important for the shoulder surgeon to be adept at recognizing and treating these tears. A combination of physical examination tests can be used to determine both the presence and size of a subscapularis tear. Compared with posterosuperior rotator cuff tears, magnetic resonance imaging detection of subscapularis is less reliable and therefore requires a high index of suspicion. Arthroscopic repair of the subscapularis presents unique challenges but can be safely and successfully performed with careful attention to detail. The results of arthroscopic subscapularis repair are encouraging at intermediate follow-up and comparable with or better than that reported with open repair. PMID- 22089283 TI - Double row repair: is it worth the hassle? AB - In the operative management of rotator cuff disease, comparable functional results have been reported after open or mini-open repair and arthroscopic fixation. Surgical repair aims to re-establish an anatomical configuration of the tendon-bone construct for restoring its mechanical performance. Single row repair is the most commonly used technique, but recently some authors have proposed to re-establish the rotator cuff footprint with 2 rows of suture anchors ("double row" repair). In regard to imaging assessment, at time zero double row repair results being more anatomic and allows for structurally sound restoration of the rotator cuff footprint. However, this does not seem to translate into superior clinical outcomes for the double row repair when evaluating all different sizes of rotator cuff tears as a whole. The scientific basis for recommending single or double row repair as preferred treatment for patients with rotator cuff tear is questionable, as minimal differences have been measured on clinical and functional rating scales. PMID- 22089284 TI - Conservative management of rotator cuff tear. AB - Ranking among the most prevalent of shoulder disorders, lesions involving shoulder rotator cuff strike million of patients in the United States at different points in their lives. Despite the fact that rotator cuff disease is a very common cause of pain and disability of the upper arm, a high proportion of patients is asymptomatic and unaware of performing daily living activities despite of a shoulder lesion. Given these drawbacks, surgeons are trying exploring whether conservative treatment is a viable option for the management of these injuries. This study presents a rationale to consider nonoperative treatment an effective option when dealing with patients with rotator cuff tears. PMID- 22089285 TI - Neoinnervation in rotator cuff tendinopathy. AB - The aim of this study was to determine whether there are more nerves in tendinopathic human tendon, and if so, where are they located. Tendon biopsies were collected from normal, tendinopathic, and torn human rotator cuff tendons and then analyzed using immunohistochemistry and antibodies against a general nerve marker (protein gene product 9.5, PGP9.5), a nerve regeneration marker (growth-associated protein 43, GAP43), and an endothelial cell marker (CD34). Nerve fibers exhibiting PGP9.5 or GAP43 immunoreactivity were often observed intimately in association with tiny blood vessels in the endotendineum of tendinopathic tendons. The expression of PGP9.5 and GAP43 were significantly higher in tendinopathic tendon compared with control tendon and torn tendon. These data support the hypothesis that early tendinopathy is associated with increases of newly grown nerve fibers and blood vessels inside and around tendinopathic tendon, and these may be the source of pain in tendinopathy. PMID- 22089286 TI - Synthetic augmentation for massive rotator cuff tears. AB - The management of massive, irreparable rotator cuff tears is challenging. They are associated with persistent defects, weakness, and poor outcomes, and can cause an uncoupling of forces across the glenohumeral joint, with unstable shoulder kinematics. There has been much interest in the development of scaffolds to bridge massive rotator cuff tears. As allograft materials may produce inflammatory responses in the host, there is notable interest in developing synthetic grafts for surgical use. Benefits and limitations of the available synthetic scaffolds for augmentation of rotator cuff tears are reported in the present review. PMID- 22089287 TI - A systematic review of the reverse shoulder replacement in rotator cuff arthropathy, rotator cuff tears, and rheumatoid arthritis. AB - The reverse shoulder arthroplasty prosthesis was originally designed for rotator cuff arthropathy, and provided good results. Over time, the indications have expanded to include, among others, irreparable rotator cuff tears and rheumatoid arthritis, and the results have become more variable. There are also fundamental differences in the designs of the original Delta III prostheses and the later developed reverse shoulder prosthesis, and many studies that provide the results in reverse shoulder arthroplasties do not consider these 2 prostheses separately. In this systematic review, we analyze the clinical outcomes of the reverse shoulder arthroplasty in rotator cuff arthropathy, rotator cuff tears without arthropathy, and rheumatoid arthritis. We also analyze the results of the 2 prostheses separately to provide a more accurate comparison. PMID- 22089288 TI - Biological resurfacing for early osteoarthritis of the shoulder. AB - Young patients with degenerative shoulder disease are a therapeutic challenge. To try to delay a shoulder arthroplasty, biological interpositional arthroplasty has been proposed to provide a biologically active bearing surface that could eventually results in the formation of fibrocartilage, fibrous tissue, or hyaline cartilage. Anterior capsule, autogenous fascia lata, Achilles tendon allograft, lateral meniscus allograft, human dermis, and porcine small intestine submucosa have been used as interposition material, either alone or in combination with a hemiarthroplasty or humeral resurfacing procedure. Some investigators have reported favorable long-term results, although others have found this procedure unreliable. Several variables are unknown at present, such as the best biological resurfacing device, healing potential, possible antigenic responses, optimal fixation technique or position, aftercare restrictions. Further prospective studies with long follow-up are necessary to provide data that will help to define the role of biological glenoid resurfacing in young patients with glenohumeral arthritis. PMID- 22089289 TI - Glenohumeral instability and rotator cuff tear. AB - The prevalence of rotator cuff tears after traumatic dislocation increases with advancing age, a likely consequence of the age-associated deterioration of the structure and mechanical properties of the tendons of the rotator cuff. These are the effective stabilizers of the glenohumeral joint, compressing the humeral head in the 3-dimensional concavity of the glenohumeral joint. It is impossible to establish whether a lesion of the capsular-labrum complex or of the rotator cuff causes or follows a dislocation, regardless of whether it is anterior or posterior. A peripheral nerve or a brachial plexus injury can be associated with tendon lesion and instability, developing the "terrible triad" of the shoulder. Both conservative and surgical management are possible, and surgeons must choose the most appropriate management modality according to the biologic age, functional demands, and type of lesion. PMID- 22089290 TI - Repair of partial tears of the rotator cuff. AB - Partial-thickness rotator cuff tears present partial disruption of tendon fibers with no communication between the subacromial bursa and the glenohumeral joint. The clinical presentation is surprisingly variable, ranging from mild discomfort to decreased throwing speed, chronic pain, and shoulder inability. The first approach to partial-thickness rotator cuff tears is usually conservative, but the hypovascularity of the critical zone and mechanical factors often result in poor spontaneous tendon healing. Surgical options include arthroscopic cuff "debridement" or "repair," performed arthroscopically or by open surgery, and subacromial decompression or debridement if necessary. No agreement has been reached on the best surgical management. However, repair is usually indicated if bursal-sided and articular tears involve more than 50% of tendon thickness; debridement is generally undertaken if <50% of the rotator cuff is torn. There is a need for randomized clinical trails formulating and testing guidelines of management and for further studies on imaging or intraoperative measures and methods to assess the thickness of the rotator cuff to inform management. PMID- 22089291 TI - Full thickness tears: retaining the cuff. AB - Repair of rotator cuff tears is technically challenging. Full thickness rotator cuff tears have no potential for spontaneous healing, no reliable tendons substitutes are available, and their management is only partially understood. Many factors seem to contribute to the final outcome, and considerable variations in the decision-making process exist. For these reasons, decisions are often taken on the basis of surgeon's clinical experience. Accurate and prompt diagnosis is fundamental to guide correct management, and the tear pattern should be carefully evaluated to planning the most appropriate repair. PMID- 22089292 TI - Management of postoperative shoulder stiffness. AB - Arthroscopic surgery has become the most popular treatment to repair rotator cuff tears. Although the exact prevalence of postoperative stiffness is unknown, many studies report an incidence rate of 4% to 15%. Management of postoperative shoulder stiffness depends on the cause of the stiffness. Nonoperative and operative management modalities are available, but postoperative shoulder stiffness is often resistant to nonsurgical management. When conservative treatment fails, surgical release of the scar tissue and adhesions can be performed both by arthroscopic or open surgery. Arthroscopic capsular release is the preferred technique for capsule contraction and adhesion formation, as it allows precise and selective debridement of the scar tissue and division of the shortened and thickened capsule by partial or extensive capsulectomy. PMID- 22089293 TI - Latissimus dorsi tendon transfer for massive irreparable rotator cuff tears: a systematic review. AB - Tendon transfers have been proposed as a possible solution to restore pain-free functions, strength, and range of motion in patients with massive and irreparable cuff tears. The aim of this review is to establish the outcomes of (1) latissimus dorsi tendon transfer (LDT-T) surgery performed as a single procedure or in combination with other muscle-tendon transfer procedures, replacement, or both; (2) LDT-T in primary and revision surgery for massive irreparable rotator cuff tears; (3) the LDT-T procedure in relation to subscapularis and teres minor integrity; (4) the LDT-T procedure in relation to the reattachment position on the humeral head of the transferred tendon; (5) the LDT-T procedure performed as a single or a double incision; (6) arthroscopic, open, or combined approach: and (7) the LDT-T procedure in patients with preoperative osteoarthritis and a nonosteoarthritic condition with the evaluation of osteoarthritis progression. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies of levels of evidence I IV were included. The LDT-T surgical procedure, outcomes, and complications were evaluated. Twenty-two studies describing 493 shoulders in 487 patients were included in our study. There were no prospective randomized, controlled studies. LDT-T is a promising strategy for the management of massive and irreparable rotator cuff tears, even though no agreement was found on several aspects and options of LDT-T. Randomized prospective control studies are still awaited on this subject. PMID- 22089296 TI - Stepwise syntheses of tri- and tetraphosphaporphyrinogens. AB - A double ring-expansion methodology allows the stepwise synthesis of tri- and tetra-phosphaporhyrinogens. Structural and calculational methods reveal extended delocalisation about their phospholide centres. PMID- 22089298 TI - The management of small sealed sources. PMID- 22089297 TI - Plasma protein binding of sorafenib, a multi kinase inhibitor: in vitro and in cancer patients. AB - Sorafenib is an orally administered multikinase inhibitor that exhibits antiangiogenic and antitumor activity. Few investigators have been able to correlate cumulative sorafenib dose or total exposure to pharmacodynamic effects. This discrepancy may be in part due to poorly understood protein binding characteristics. Since unbound drug concentrations are believed to be more relevant to pharmacological and toxicological responses than total drug, an equilibrium dialysis method using 96-well microdialysis plates was optimized and validated for determining the fraction unbound (F(u)) sorafenib in human plasma and in isolated protein solutions. Unbound sorafenib concentrations were determined in cancer patients receiving the drug orally at a dose of 400 mg and 600 mg twice daily. Sorafenib was extensively bound with mean F(u) value of 0.3% in both non-cancer and cancer patient's plasma. The binding in plasma was concentration independent, indicating a low-affinity, possibly nonspecific and nonsaturable process. In isolated protein solutions, 99.8% and 79.3% of sorafenib was bound to human serum albumin (HSA) (4 g/dL) and alpha(1)-acid glycoprotein (AAG) (0.1 g/dL) with binding constants of 1.24 * 10(6) M(-1) and 1.40 * 10(5) M( 1), respectively. In cancer patients receiving sorafenib, unbound sorafenib was not correlated with patient characteristics or laboratory values. In conclusion, sorafenib is highly protein bound in human plasma with a higher affinity towards albumin and limited free drug may be partly responsible for its borderline clinical activity. PMID- 22089299 TI - Concussion (mild traumatic brain injury) and the team physician: a consensus statement--2011 update. PMID- 22089302 TI - Effects of dynamic exercise on plasma arachidonic acid epoxides and diols in human volunteers. AB - Metabolites of the cytochrome P450 (CYP) pathway may contribute to vasodilation of the vasculature. However, it is not known whether exercise affects their circulating concentrations. The authors determined effects of exercise intensity and duration on plasma concentrations of epoxy and dihydroxy metabolites of arachidonic acid. Their goal was to delineate the threshold workload, optimal workload, and duration required to produce increases in plasma concentrations of these vasoactive substances. Healthy volunteers (N = 14) performed maximal exercise testing on a bicycle ergometer during Visit 1. On separate days, subjects cycled for 20 min at 30%, 60%, and 80% of their maximal exercise intensity. The last day consisted of 40 min of exercise at 60% of maximal exercise intensity. Venous blood was obtained before, during, and after exercise for analysis. Compared with rest, increases were observed during the 80% workload at 20 min postexercise -14,15-DHET (0.77 +/- 0.21 vs. 0.93 +/- 0.27 nM) - and at 2 min postexercise: 11,12-DHET (0.64 +/- 0.22 vs. 0.71 +/- 0.24 nM; p < .05). Also compared with rest, 40-min values during the 60% workload were 14,15-DHET 0.79 +/- 0.22 vs. 0.91 +/- 0.31 nM and at 2 min post 14,15 EET 0.12 +/- 0.06 vs. 0.21 +/- 0.16 nM (p < .05). Results suggest the CYP metabolites (i.e., DHETs) are released during short-term high-intensity and long-term moderate-intensity exercise. PMID- 22089303 TI - Unilateral fluid absorption and effects on peak power after ingestion of commercially available hypotonic, isotonic, and hypertonic sports drinks. AB - Isotonic sports drinks are often consumed to offset the effects of dehydration and improve endurance performance, but hypotonic drinks may be more advantageous. The purpose of the study was to compare absorption and effects on performance of a commercially available hypotonic sports drink (Mizone Rapid: 3.9% carbohydrate [CHO], 218 mOsmol/kg) with those of an isotonic drink (PowerAde: 7.6% CHO, 281 mOsmol/ kg), a hypertonic drink (Gatorade: 6% CHO, 327 mOsmol/kg), and a noncaloric placebo (8 mOsmol/kg). In a crossover, 11 cyclists consumed each drink on separate days at 250 ml/15 min during a 2-hr preload ride at 55% peak power followed by an incremental test to exhaustion. Small to moderate increases in deuterium oxide enrichment in the preload were observed with Mizone Rapid relative to PowerAde, Gatorade, and placebo (differences of 88, 45, and 42 parts per million, respectively; 90% confidence limits +/-28). Serum osmolality was moderately lower with Mizone Rapid than with PowerAde and Gatorade (-1.9, -2.4; mOsmol/L; +/-1.2 mOsmol/L) but not clearly different vs. placebo. Plasma volume reduction was small to moderate with Mizone Rapid, PowerAde, and Gatorade relative to placebo (-1.9%, -2.5%, -2.9%; +/- 2.5%). Gut comfort was highest with Mizone Rapid but clearly different (8.4% +/- 4.8%) only vs PowerAde. Peak power was highest with Mizone Rapid (380 W) vs. placebo and other drinks (1.2-3.0%; 99% confidence limits +/-4.7%), but differences were inconclusive with reference to the smallest important effect (~1.2%). The outcomes are consistent with fastest fluid absorption with the hypotonic sports drink. Further research should determine whether the effect has a meaningful impact on performance. PMID- 22089304 TI - Case study: nutrition challenges of a marathon runner with a gastric bypass. AB - A new type of athlete is appearing in the offices of sports dietitians: formerly obese people who have undergone gastric bypass surgery and now aspire to be marathoners, triathletes, and other types of endurance athletes. The standard nutrition advice offered to bypass patients is contrary to the standard sports advice given to athletes. Bypass athletes need to limit carbohydrates, fluids, and energy intake and consume a protein-based diet. This case study describes the sport nutrition concerns of a woman who, after having gastric bypass surgery, trained to run a marathon (42 km). Because of her limited ability to consume food and fluids, she experienced difficulty preventing fatigue and dehydration during her long training runs and the marathon itself. She learned through trial and error how to survive the nutritional challenges and complete the marathon. Health professionals need to be aware of the potential medical risks associated with endurance exercise in gastric bypass patients. Research is needed to determine the best sports nutrition practices for bypass patients. Only then can sport dietitians better educate this small but growing contingent of endurance athletes so the athletes can meet their training and performance goals and reduce their risk of experiencing serious health consequences. PMID- 22089305 TI - N-Acetylcysteine's attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situations. AB - Production of reactive oxygen species (ROS) during muscle contractions is associated with muscle fatigue and damage in the short term and adaptive responses in the long term. When adaptation is inconsequential acute antioxidant supplementation may be able to attenuate muscle fatigue and damage to enhance performance. This study aimed to determine the effects of acute oral N acetylcysteine (NAC) supplementation on Yo-Yo Intermittent Recovery Test Level 1 (YIRT-L1) performance after repeated bouts of damaging intermittent exercise. In a pair-matched design, 12 recreationally trained men engaged in 6 d of either NAC (n = 6) or placebo (n = 6) supplementation. After a treatment-loading day, participants completed 3 testing sessions, on alternating days, consisting of a preexercise isokinetic dynamometry (IKD) test, a damaging intermittent-exercise protocol, YIRT-L1, and a postexercise IKD test. Another IKD test was completed on the 2 intervening d. NAC treatment resulted in a significant preservation of YIRT L1 performance (p <= .0005). IKD performance significantly deteriorated over time at all contraction speeds, and this deterioration was not influenced by treatment group. Plasma creatine kinase values increased significantly over time (p = .002) and were significantly greater in the NAC group than in the placebo group (p = .029). NAC induced mild gastrointestinal side effects. NAC supplementation may be a useful strategy to enhance performance during short-term competitive situations when adaption is inconsequential. Titration studies to elucidate a treatment dose that enhances performance without inducing side effects are now required. PMID- 22089306 TI - Muscle-fiber type and blood oxidative stress after eccentric exercise. AB - Acute strength exercise elicits a transient oxidative stress, but the factors underlying the magnitude of this response remain unknown. The purpose of this investigation was to determine whether muscle-fiber type relates to the magnitude of blood oxidative stress after eccentric muscle activity. Eleven college-age men performed 3 sets of 50 eccentric knee-extensions. Blood samples taken pre-, post , and 24, 48, 72, and 96 hr postexercise were assayed for comparison of muscle damage and oxidative-stress biomarkers including protein carbonyls (PCs). Vastus lateralis muscle biopsies were assayed for relative percentage of slow- and fast twitch muscle fibers. There was a mixed fiber composition (Type I = 39.6% +/- 4.5%, Type IIa = 35.7% +/- 3.5%, Type IIx = 24.8% +/- 3.8%; p = .366). PCs were elevated 24, 48, and 72 hr (p = .032) postexercise, with a peak response of 126% (p = .012) above baseline, whereas other oxidative-stress biomarkers were unchanged. There are correlations between Type II muscle-fiber type and postexercise PC. Further study is needed to understand the mechanisms responsible for the observed fast-twitch muscle-fiber oxidative-stress relationship. PMID- 22089307 TI - Fluid balance and sodium losses during indoor tennis match play. AB - This study assessed fluid balance, sodium losses, and effort intensity during indoor tennis match play (17 +/- 2 degrees C, 42% +/- 9% relative humidity) over a mean match duration of 68.1 +/- 12.8 min in 16 male tennis players. Ad libitum fluid intake was recorded throughout the match. Sweat loss from change in nude body mass; sweat electrolyte content from patches applied to the forearm, calf, and thigh, and back of each player; and electrolyte balance derived from sweat, urine, and daily food-intake analysis were measured. Effort intensity was assessed from on-court heart rate compared with data obtained during a maximal treadmill test. Sweat rate (M +/- SD) was 1.1 +/- 0.4 L/hr, and fluid-ingestion rate was 1.0 +/- 0.6 L/hr (replacing 93% +/- 47% of fluid lost), resulting in only a small mean loss in body mass of 0.15% +/- 0.74%. Large interindividual variabilities in sweat rate (range 0.3-2.0 L/hr) and fluid intake (range 0.31 2.52 L/hr) were noted. Whole-body sweat sodium concentration was 38 +/- 12 mmol/L, and total sodium losses during match play were 1.1 +/- 0.4 g (range 0.5 1.8 g). Daily sodium intake was 2.8 +/- 1.1 g. Indoor match play largely consisted of low-intensity exercise below ventilatory threshold (mean match heart rate was 138 +/- 24 beats/min). This study shows that in moderate indoor temperature conditions players ingest sufficient fluid to replace sweat losses. However, the wide range in data obtained highlights the need for individualized fluid-replacement guidance. PMID- 22089308 TI - Impact of iron depletion without anemia on performance in trained endurance athletes at the beginning of a training season: a study of female collegiate rowers. AB - The objective of this study was to determine the impact of iron depletion without anemia on performance in a sample of female collegiate rowers at the beginning of a training season (August 2008, January 2009, and September 2009). One hundred sixty-five female collegiate rowers from 5 colleges and universities in central New York State participated in a screening of iron status. Blood hemoglobin (Hgb), serum ferritin (sFer), and soluble transferrin receptor were measured to determine prevalence of iron depletion and anemia. Rowers' habitual moderate and vigorous physical activity, as well as their best time to complete a 2-km simulated race during the previous 3 months, were self-reported. Sixteen rowers (10%) were identified as anemic (Hgb <12.0 g/dl). Using a sFer cutoff of <20.0 MUg/L, 30% (n = 44) of the nonanemic rowers were identified as iron depleted without anemia and reported 2-km times ~21 s slower (p < .004) than rowers with normal iron status. Given the high prevalence of iron depletion reported in this and other studies, screening for low iron stores at the start of a training program in female athletes involved in an endurance sport may be clinically useful. In this study, iron-depleted rowers (sFer <20-25 MUg/L) reported a decrease in performance time compared with those with normal iron stores. PMID- 22089309 TI - Nutrition status of junior elite Canadian female soccer athletes. AB - CONTEXT: Adolescent female team-sport athletes are faced with the challenge of meeting nutrition requirements for growth and development, as well as sport performance. There is a paucity of evidence describing the dietary adequacy of this population in respect to these physiological demands. Therefore, the aim of this study was to comprehensively evaluate the nutrition status of junior elite female soccer athletes. METHOD: A total of 33 athletes (15.7 +/- 0.7 yr) completed anthropometric assessment, 4-day food records analyzed for macro- and micronutrient intake, and hematological analysis. Energy expenditure was estimated using predictive equations. RESULTS: Mean sum of 7 skinfolds was 103.1 +/- 35.2 mm, and body-mass index was 22.7 +/- 2.7. Mean energy intake was 2,079 +/- 460 kcal/day, and estimated energy expenditure was 2,546 +/- 190 kcal/day. Of the athletes, 51.5% consumed <5g/kg carbohydrate, 27.3% consumed <1.2g/kg protein, and 21.2% consumed <25% of energy intake from fat. A large proportion of athletes did not meet Dietary Reference Intakes for pantothenic acid (54.5%), vitamin D (100%), folate (69.7%), vitamin E (100%), and calcium (66.7%). Compared with recommendations for athletes, 89.3% and 50.0% of participants had depleted iron and 25-hydroxyvitamin D, respectively. CONCLUSION: A high proportion of players were not in energy balance, failed to meet carbohydrate and micronutrient recommendations, and presented with depleted iron and vitamin D status. Suboptimal nutrition status may affect soccer performance and physiological growth and development. More research is needed to understand the unique nutrition needs of this population and inform sport nutrition practice and research. PMID- 22089310 TI - Case study: simulated and real-life energy expenditure during a 3-week expedition. AB - During prolonged periods of high energy expenditure (EE), restricted food intake can lead to a loss of body mass. This case study describes the preexpedition support for an unsupported 3-wk crossing of the Atacama Desert in Chile. The goals were to simulate the energy requirements of walking under varying conditions and to predict energy intake and EE to evaluate whether the expected weight loss was in acceptable limits. The expeditionist (male, 35 yr, 197 cm, basal weight 80 +/- 0.5 kg) was a well-trained endurance athlete with experience of multiple expeditions. During the simulation, he walked on a treadmill at speeds of 2-7 km/hr under varying conditions of inclination (0%, 7.5%), backpack weight (0 kg, 30 kg), and altitude (sea level, simulated altitude of 3,500 m). Under all conditions, the lowest EE was observed at 5 km/ hr. Based on the simulation data, we predicted an average EE of 4,944 kcal/day for the expedition. Because energy intake was restricted to 2,249 kcal/day, we expected the expeditionist to lose considerable weight and consequently advised him to gain 5 kg of body-fat reserves. During the actual desert crossing, he covered a distance of 26 +/- 7 km/day at an average speed of 3.8 +/- 0.4 km/hr. Daily EE (4,817 +/- 794 kcal/day) exceeded energy intake (1,771 +/- 685 kcal/day), and the negative energy balance was in agreement with the actual weight loss of 10.5 kg, which was most notable in the lower trunk. PMID- 22089311 TI - Proceedings of the XX Congress of the Italian Society for Pure and Applied Biophysics (SIBPA) Arcidosso (Gr), Italy, September 2010. PMID- 22089313 TI - Isolation and characterization of main group and late transition metal complexes using orthometallated imine ligands. AB - Several late transition metal and main group orthometallated imine complexes were synthesized by utilizing ortholithiated imine precursors. Magnesium, aluminum, zinc, copper(I), and tin(IV) complexes were isolated and characterized. Subsequent reactions with electrophiles such as Ph(2)PCl, MeI and I(2) yielded several functionalized products, including a new iminophosphine ligand and its corresponding copper(I) complex. The coordination modes of the orthometallated imine ligands, as well as the structures of the metal complexes, were studied in the solid state using small molecule X-ray diffraction when possible. PMID- 22089314 TI - Gene-centric analysis of serum cotinine levels in African and European American populations. AB - To date, most genetic association studies of tobacco use have been conducted in European American subjects using the phenotype of smoking quantity (cigarettes per day). However, smoking quantity is a very imprecise measure of exposure to tobacco smoke constituents. Analyses of alternate phenotypes and populations may improve our understanding of tobacco addiction genetics. Cotinine is the major metabolite of nicotine, and measuring serum cotinine levels in smokers provides a more objective measure of nicotine dose than smoking quantity. Previous genetic association studies of serum cotinine have focused on individual genes. We conducted a genetic association study of the biomarker in African American (N=365) and European American (N=315) subjects from the Coronary Artery Risk Development in Young Adults study using a chip containing densely-spaced tag SNPs in ~2100 genes. We found that rs11187065, located in the non-coding region (intron 1) of insulin-degrading enzyme (IDE), was the most strongly associated SNP (p=8.91 * 10(-6)) in the African American cohort, whereas rs11763963, located on chromosome 7 outside of a gene transcript, was the most strongly associated SNP in European Americans (p=1.53 * 10(-6)). We then evaluated how the top variant association in each population performed in the other group. We found that the association of rs11187065 in IDE was also associated with the phenotype in European Americans (p=0.044). Our top SNP association in European Americans, rs11763963 was non-polymorphic in our African American sample. It has been previously shown that psychostimulant self-administration is reduced in animals with lower insulin because of interference with dopamine transmission in the brain reward centers. Our finding provides a platform for further investigation of this, or additional mechanisms, involving the relationship between insulin and self-administered nicotine dose. PMID- 22089315 TI - R7BP modulates opiate analgesia and tolerance but not withdrawal. AB - The adaptor protein R7 family binding protein (R7BP) modulates G protein coupled receptor (GPCR) signaling and desensitization by controlling the function of regulator of G protein signaling (RGS) proteins. R7BP is expressed throughout the brain and appears to modulate the membrane localization and stability of three proteins that belong to R7 RGS family: RGS6, RGS7, and RGS9-2. RGS9-2 is a potent negative modulator of opiate and psychostimulant addiction and promotes the development of analgesic tolerance to morphine, whereas the role of RGS6 and RGS7 in addiction remains unknown. Recent studies revealed that functional deletion of R7BP reduces R7 protein activity by preventing their anchoring to the cell membrane and enhances GPCR responsiveness in the basal ganglia. Here, we take advantage of R7BP knockout mice in order to examine the way interventions in R7 proteins function throughout the brain affect opiate actions. Our results suggest that R7BP is a negative modulator of the analgesic and locomotor activating actions of morphine. We also report that R7BP contributes to the development of morphine tolerance. Finally, our data suggest that although prevention of R7BP actions enhances the analgesic responses to morphine, it does not affect the severity of somatic withdrawal signs. Our data suggest that interventions in R7BP actions enhance the analgesic effect of morphine and prevent tolerance, without affecting withdrawal, pointing to R7BP complexes as potential new targets for analgesic drugs. PMID- 22089316 TI - Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence. AB - The wars in Iraq and Afghanistan are associated with high rates of post-traumatic stress disorder (PTSD) and comorbid alcohol use disorders. The pharmacotherapy of these comorbid conditions has received relatively little study. The current study compared the serotonin uptake inhibitor, paroxetine, to the norepinephrine uptake inhibitor, desipramine. It also evaluated the adjunctive efficacy of the Food and Drug Administration (FDA)-approved alcoholism pharmacotherapy, naltrexone, relative to placebo. Four groups of predominately male veterans (n=88) meeting current diagnostic criteria for both alcohol dependence (AD) and PTSD were randomly assigned under double-blind conditions to one of four groups: paroxetine+naltrexone; paroxetine+placebo; desipramine+naltrexone; desipramine+placebo. Main outcome measures included standardized scales that assessed symptoms of PTSD and alcohol consumption. Paroxetine did not show statistical superiority to desipramine for the treatment of PTSD symptoms. However, desipramine was superior to paroxetine with respect to study retention and alcohol use outcomes. Naltrexone reduced alcohol craving relative to placebo, but it conferred no advantage on drinking use outcomes. Although the serotonin uptake inhibitors are the only FDA-approved medications for the treatment of PTSD, the current study suggests that norepinephrine uptake inhibitors may present clinical advantages when treating male veterans with PTSD and AD. However, naltrexone did not show evidence of efficacy in this population. This study was registered with ClinicalTrials.gov, registration number NCT00338962 and URL: http://clinicaltrials.gov/ct2/show/NCT00338962?term=desipramine+AND+alcohol+depen ence+AND+depression&recr=Closed&rank=1. PMID- 22089317 TI - Is cognitive functioning impaired in methamphetamine users? A critical review. AB - The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition. Included in the discussion are findings from studies that have assessed the acute and long-term effects of methamphetamine on several domains of cognition, including visuospatial perception, attention, inhibition, working memory, long-term memory, and learning. In addition, relevant neuroimaging data are reviewed in an effort to better understand neural mechanisms underlying methamphetamine-related effects on cognitive functioning. In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures. More importantly, however, the clinical significance of these findings may be limited because cognitive functioning overwhelmingly falls within the normal range when compared against normative data. In spite of these observations, there seems to be a propensity to interpret any cognitive and/or brain difference(s) as a clinically significant abnormality. The implications of this situation are multiple, with consequences for scientific research, substance-abuse treatment, and public policy. PMID- 22089318 TI - Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids. AB - Csnk1e, the gene encoding casein kinase 1-epsilon, has been implicated in sensitivity to amphetamines. Additionally, a polymorphism in CSNK1E was associated with heroin addiction, suggesting that this gene may also affect opioid sensitivity. In this study, we first conducted genome-wide quantitative trait locus (QTL) mapping of methamphetamine (MA)-induced locomotor activity in C57BL/6J (B6) * DBA/2J (D2)-F(2) mice and a more highly recombinant F(8) advanced intercross line. We identified a QTL on chromosome 15 that contained Csnk1e (63 86 Mb; Csnk1e=79.25 Mb). We replicated this result and further narrowed the locus using B6.D2(Csnk1e) and D2.B6(Csnk1e) reciprocal congenic lines (78-86.8 and 78.7 81.6 Mb, respectively). This locus also affected sensitivity to the MU-opioid receptor agonist fentanyl. Next, we directly tested the hypothesis that Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids. Mice harboring a null allele of Csnk1e showed an increase in locomotor activity following MA administration. Consistent with this result, coadministration of a selective pharmacological inhibitor of Csnk1e (PF-4800567) increased the locomotor stimulant response to both MA and fentanyl. These results show that a narrow genetic locus that contains Csnk1e is associated with differences in sensitivity to MA and fentanyl. Furthermore, gene knockout and selective pharmacological inhibition of Csnk1e define its role as a negative regulator of sensitivity to psychostimulants and opioids. PMID- 22089319 TI - Pharmacological activation of group-II metabotropic glutamate receptors corrects a schizophrenia-like phenotype induced by prenatal stress in mice. AB - Prenatal exposure to restraint stress causes long-lasting changes in neuroplasticity that likely reflect pathological modifications triggered by early life stress. We found that the offspring of dams exposed to repeated episodes of restraint stress during pregnancy (here named 'prenatal restraint stress mice' or 'PRS mice') developed a schizophrenia-like phenotype, characterized by a decreased expression of brain-derived neurotrophic factor and glutamic acid decarboxylase 67, an increased expression of type-1 DNA methyl transferase (DNMT1) in the frontal cortex, and a deficit in social interaction, locomotor activity, and prepulse inhibition. PRS mice also showed a marked decrease in metabotropic glutamate 2 (mGlu2) and mGlu3 receptor mRNA and protein levels in the frontal cortex, which was manifested at birth and persisted in adult life. This decrease was associated with an increased binding of DNMT1 to CpG-rich regions of mGlu2 and mGlu3 receptor promoters and an increased binding of MeCP2 to the mGlu2 receptor promoter. Systemic treatment with the selective mGlu2/3 receptor agonist LY379268 (0.5 mg/kg, i.p., twice daily for 5 days), corrected all the biochemical and behavioral abnormalities shown in PRS mice. Our data show for the first time that PRS induces a schizophrenia-like phenotype in mice, and suggest that epigenetic changes in mGlu2 and mGlu3 receptors lie at the core of the pathological programming induced by early-life stress. PMID- 22089320 TI - Compound stimulus presentation and the norepinephrine reuptake inhibitor atomoxetine enhance long-term extinction of cocaine-seeking behavior. AB - Drug abstinence is frequently compromised when addicted individuals are re exposed to environmental stimuli previously associated with drug use. Research with human addicts and in animal models has demonstrated that extinction learning (non-reinforced cue-exposure) can reduce the capacity of such stimuli to induce relapse, yet extinction therapies have limited long-term success under real-world conditions (Bouton, 2002; O'Brien, 2008). We hypothesized that enhancing extinction would reduce the later ability of drug-predictive cues to precipitate drug-seeking behavior. We, therefore, tested whether compound stimulus presentation and pharmacological treatments that augment noradrenergic activity (atomoxetine; norepinephrine reuptake inhibitor) during extinction training would facilitate the extinction of drug-seeking behaviors, thus reducing relapse. Rats were trained that the presentation of a discrete cue signaled that a lever press response would result in cocaine reinforcement. Rats were subsequently extinguished and spontaneous recovery of drug-seeking behavior following presentation of previously drug-predictive cues was tested 4 weeks later. We find that compound stimulus presentations or pharmacologically increasing noradrenergic activity during extinction training results in less future recovery of responding, whereas propranolol treatment reduced the benefit seen with compound stimulus presentation. These data may have important implications for understanding the biological basis of extinction learning, as well as for improving the outcome of extinction-based therapies. PMID- 22089321 TI - The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease. AB - Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward. PMID- 22089323 TI - Generation of normative pediatric skull models for use in cranial vault remodeling procedures. AB - PURPOSE: While the goal of craniofacial reconstruction surgery is to restore the cranial head shape as much towards normal as possible, for the individual patient, there is, in fact, no normal three-dimensional (3D) model to act as a guide. In this project, we generated a library of normative pediatric skulls from which a guiding template could be fabricated for a more standardized, objective and precise correction of craniosynostosis. METHODS: Computed tomography data from 103 normal subjects aged 8-12 months were compiled and a 3D computational model of the skull was generated for each subject. The models were mathematically registered to a baseline model for each month of age within this range and then averaged, resulting in a single 3D point cloud. An external cranial surface was subsequently passed through the point cloud and its shape and size customized to fit the head circumference of individual patients. RESULTS: The resultant fabricated skull models provide a novel and applicable tool for a detailed, quantitative comparison between the normative and patient skulls for preoperative planning and practice for a variety of craniofacial procedures including vault remodeling. Additionally, it was possible to extract the suprafrontal orbit anatomy from the normative model and fabricate a bandeau template to guide intraoperative reshaping. CONCLUSIONS: Normative head shapes for pediatric patients have wide application for craniofacial surgery including planning, practice, standarized operative repair, and standardized measurement and reporting of outcomes. PMID- 22089322 TI - Quantitative tract-specific measures of uncinate and cingulum in major depression using diffusion tensor imaging. AB - Previous findings suggested the role of the prefrontal cortex, hippocampus, and cingulate gyrus in major depressive disorders (MDD), but the white matter microstructural abnormalities of the fibers connecting these brain structures are not known. The purpose of this study was to test the hypothesis that white matter abnormalities are present in association fibers of the uncinate fasciculus (UF) and cingulum bundle (CB) among MDD subjects. A total of 21 MDD subjects aged between 30 and 65 years and 21 age-matched healthy controls (HC) were recruited. All subjects were right-handed and without history of diabetes or other cardiac diseases. We extracted quantitative tract-specific measures based on diffusion tensor imaging tractography to examine both diffusivity and geometric properties of the UF and CB. Significantly decreased fractional anisotropy (FA) and increased radial diffusivity of the right UF were observed in MDD patients compared with HC (p<0.05), while their geometric characteristics remained relatively unchanged. Among MDD subjects, depression severity had a significant negative correlation with normalized number of fibers (NNF) in the right UF (r= 0.53, p=0.02). We also found significant age effect (oldR) in both groups in the FA measure of the CB. Our study demonstrates novel findings of white matter microstructural abnormalities of the right UF in MDD. In the MDD group, the severity of depression is associated with reduced NNF in the right UF. These findings have implications for both clinical manifestations of depression as well as its pathophysiology. PMID- 22089324 TI - Success of pure neuroendoscopic technique in the treatment of Sylvian arachnoid cysts in children. AB - INTRODUCTION: Neuroendoscopic approaches to Sylvian arachnoid cysts (SACs) constitute an alternative treatment option to craniotomy for fenestration and shunting procedures. In this study, the authors discuss their experience on pure neuroendoscopic technique in the treatment of SACs in children. RESULTS: The results of treatment of 20 children (range of age, between 7 months and 17 years) with Galassi type II (n, 5) or III (n, 15) SACs who were subjected to pure neuroendoscopic fenestration procedure were presented. It was possible to perform the cystocisternostomy endoscopically in all children with several stomies. The site of the opening was between the optic nerve and the carotid artery in 19, between the carotid artery and the oculomotor nerve in 17, and below the oculomotor nerve in 7. The stomies were enlarged in all cases using the double balloon. Three of the cases required repetition of the operation and two cases required "cystoperitoneal shunt" implantation. There was one minor complication in a patient who had an asymptomatic postoperative subdural effusion, which resolved spontaneously. Of the 18 cases, in which the neuroendoscopic procedures succeeded, 10 showed a reduction in cyst size. The mean follow-up period was 53 months. DISCUSSION: Our results suggest that "pure neuroendoscopic" approach can be used safely in the management of SACs in children. We recommend at least two fenestration sites for an effective marsupialization of the cyst within the basal cisterns. In pediatric cases, the use of a small diameter rigid endoscope allows to reach safely the planned target areas. PMID- 22089325 TI - Do women pretend orgasm to retain a mate? AB - The current study tested the hypothesis that women pretend orgasm as part of a broader strategy of mate retention. We obtained self-report data from 453 heterosexual women (M age, 21.8 years) in a long-term relationship (M length, 32.8 months) drawn from universities and surrounding communities in the southeastern United States. The results indicated that (1) women who perceived higher risk of partner infidelity were more likely to report pretending orgasm, (2) women who reported greater likelihood of pretending orgasm also reported performing more mate retention behaviors, and (3) women's perceptions of partner infidelity risk mediated the relationship between pretending orgasm and the performance of cost-inflicting mate retention behaviors, such as Intersexual Negative Inducements ("Flirted with someone in front of my partner") and Intrasexual Negative Inducements ("Yelled at a woman who looked at my partner"). Thus, pretending orgasm may be part of a broader strategy of mate retention performed by women who perceive higher risk of partner infidelity. PMID- 22089326 TI - Comparison between intraoperative fentanyl and tramadol to improve quality of emergence. AB - BACKGROUND: Cough causes poor quality of emergence from anesthesia and risks of several complications. We compared fentanyl and an antitussive action of tramadol on the quality of emergence and postoperative outcome. METHODS: A total of 110 adults (18 to 83 y) of American Society of Anesthesiologists physical status I III undergoing elective lumbar microdiscectomy with intubated total intravenous anesthesia were randomly divided into 2 groups of 55 each. The patients assigned to the fentanyl group received a dose of 1 MUg/kg of fentanyl, whereas those assigned to the tramadol group received 1 mg/kg of tramadol, at the beginning of skin closure. We recorded the incidence of cough, quality of extubation at fixed times, maximal heart rates, maximal blood pressure during emergence, postoperative pain scores, and consumption of fentanyl. In addition, postoperative sore throat (POST), hoarseness, postoperative nausea and vomiting, and other anesthetic and surgical-related complications were recorded. RESULTS: Tramadol reduced cough incidence, improved extubation quality, and provided more stable hemodynamics during emergence. There was no significant difference in postoperative pain, fentanyl consumption, incidence and severity of POST, hoarseness, and postoperative nausea and vomiting between groups. Moreover, we found that the incidence of POST did not correlate with cough incidence. CONCLUSIONS: A dose of 1 mg/kg of tramadol administered intravenously 30 minutes before the expected extubation, compared with 1 MUg/kg of fentanyl, decreased cough incidence, improved emergence quality, and provided stable hemodynamics. However, there was no significant difference between tramadol and fentanyl in pain scores and fentanyl consumption postoperatively. PMID- 22089327 TI - Transient infrared spectroscopy: a new approach to investigate valence tautomerism. AB - In this work we present, to our knowledge for the first time, the results of a transient infrared spectroscopic study of the photoinduced valence tautomerism process in cobalt-dioxolene complexes with sub-picosecond time resolution. The molecular systems investigated were [Co(tpa)(diox)]PF(6) (1) and [Co(Me(3)tpa)(diox)]PF(6) (2), where diox = 3,5-di-tert-butyl-1,2-dioxolene; tpa = tris(2-pyridylmethyl)amine and Me(3)tpa its 6-methylated analogue. Complex (1) is present in solution as ls-Co(III)(catecholate) (1-CAT), while (2) as hs Co(II)(semiquinonate) (2-SQ). DFT calculation of the harmonic frequencies for (1) and (2) allowed us to identify the vibrational markers of catecholate and semiquinonate redox isomers. Irradiation with 405 and 810 nm pulses (~35 fs) of (1-CAT) induces the formation of an intermediate excited species from which the ground state population is recovered with a time constant of 1.5 +/- 0.3 ns. Comparing the 1 ns transient infrared spectrum with the experimental difference spectrum FTIR(2-SQ)-FTIR(1-CAT) and with the calculated difference spectrum IR(c)(1-SQ)-IR(c)(1-CAT) we are able to unequivocally identify the long lived species as the semiquinonate redox isomer of (1). On the other hand, no evidence of photoconversion is observed upon irradiation of (2) with 405 nm. Temporal evolution of transient spectra was analyzed with the combined approach consisting of singular values decomposition and global fitting (global analysis). After 405 and 810 nm excitation of (1-CAT), the semiquinonate excited species is formed on an ultrafast time scale (<200 fs) and cools down within the first 50 ps. Excitation of (2-SQ) with 405 nm wavelength produces a short lived excited state in which the semiquinonate nature of dioxolene is preserved and the ground state recovery is completed within 30 ps. PMID- 22089328 TI - Rasburicase for hyperuricemia in hemolytic uremic syndrome. AB - BACKGROUND: Acute kidney injury (AKI) with elevated serum uric acid (UA) levels has been reported in patients with hemolytic uremic syndrome (HUS). AKI is thought to result from tubular obstruction by UA crystals. Inducing a diuresis may ameliorate the oligoanuria in such patients. We describe a child with HUS in whom reducing UA with fluids and rasburicase appeared to accelerate the recovery of renal function. CASE-DIAGNOSIS/TREATMENT: A 9-month-old Caucasian male infant presented with 6 days of diarrhea, 3 days of vomiting, and 24 h of oliguria. On admission, hemoglobin was 8.3 g/dL, platelet count 36,000/L, blood urea nitrogen 73 mg/dL, and serum creatinine (SCr) 2.7 mg/dL. Diarrhea-associated HUS was diagnosed. The day after admission, SCr was 2.9 mg/dL and UA 12.3 mg/dL. On hospital day 2, he received a dose of intravenous rasburicase 0.18 mg/kg, and less than 12 h later, the UA had fallen to 0.3 mg/dL. The SCr level also started to fall, and urine output progressively increased without the use of diuretics. Renal function continued to improve, and the UA level remained normal despite ongoing hemolysis requiring a second red blood cell transfusion on hospital day 5. The patient was discharged on hospital day 7 in good physical condition. Two months later, he was in good health, with a SCr level of 0.2 mg/dL and UA of 4.2 mg/dL. CONCLUSIONS: We postulate that aggressive management of the high serum UA level with rasburicase and fluid hydration accelerated the recovery of our patient. Further studies are needed to determine the role of rasburicase in the treatment of hyperuricemia in patients with HUS. PMID- 22089329 TI - Rapid identification of neuraminidase inhibitor resistance mutations in seasonal influenza virus A(H1N1), A(H1N1)2009, and A(H3N2) subtypes by melting point analysis. AB - The high mutation rate of influenza virus, combined with the increasing worldwide use of influenza virus-specific drugs, allows the selection of viruses that are resistant to the currently available antiviral medications. Therefore, reliable tests for the rapid detection of drug-resistant influenza virus strains are required. We evaluated the use of a procedure involving real-time polymerase chain reaction (PCR) followed by melting point analysis (MPA) of hybrids formed between the PCR product and a specific oligonucleotide probe for the identification of point mutations in the influenza A virus neuraminidase gene (NA) that are associated with oseltamivir resistance [resulting in the amino acid change H275Y for seasonal and pandemic influenza A(H1N1) viruses and E119V for A(H3N2) viruses]. Therefore, 54 seasonal A(H1N1) (12 oseltamivir-resistant and 42 sensitive strains), 222 A(H1N1)2009 (5 resistant, 217 sensitive), and 51 A(H3N2) viruses (2 resistant, 49 sensitive) were tested by MPA, and the results were compared to those obtained by sequencing the NA gene. The results clearly indicate that the identification of drug resistance mutations by MPA is as accurate as sequencing, irrespective of whether MPA is performed using clinical material or the corresponding isolate. MPA enables a clear identification of mutations associated with antiviral resistance. PMID- 22089330 TI - QTL mapping for seedling traits in wheat grown under varying concentrations of N, P and K nutrients. AB - Nutrient use efficiency (NuUE), comprising nutrient uptake and utilization efficiency, is regarded as one of the most important factors for wheat yield. In the present study, six morphological, nine nutrient content and nine nutrient utilization efficiency traits were investigated at the seedling stage using a set of recombinant inbred lines (RILs), under hydroponic culture of 12 treatments including single nutrient levels and two- and three-nutrient combinations treatments of N, P and K. For the 12 designed treatments, a total of 380 quantitative trait loci (QTLs) on 20 chromosomes for the 24 traits were detected. Of these, 87, 149 and 144 QTLs for morphological, nutrient content and nutrient utilization efficiency traits were found, respectively. Using the data of the average value (AV) across 12 treatments, 70 QTLs were detected for 23 traits. Most QTLs were located in new marker regions. Twenty-six important QTL clusters were mapped on 13 chromosomes, 1A, 1B, 1D, 2B, 3A, 3B, 4A, 4B, 5D, 6A, 6B, 7A and 7B. Of these, ten clusters involved 147 QTLs (38.7%) for investigated traits, indicating that these 10 loci were more important for the NuUE of N, P and K. We found evidence for cooperative uptake and utilization (CUU) of N, P and K in the early growth period at both the phenotype and QTL level. The correlation coefficients (r) between nutrient content and nutrient utilization efficiency traits for N, P and K were almost all significantly positive correlations. A total of 32 cooperative CUU loci (L1-L32) were found, which included 190 out of the 293 QTLs (64.8%) for the nutrient uptake and utilization efficiency traits, indicating that the CUU-QTLs were common for N, P and K. The CUU-QTLs in L3, L7, L16 and L28 were relatively stable. The CUU-QTLs may explain the CUU phenotype at the QTL level. PMID- 22089331 TI - Human miR-31 targets radixin and inhibits migration and invasion of glioma cells. AB - MicroRNAs (miRNAs) are a novel group of short RNAs, about 20-22 nucleotide in length, that regulate gene expression in a post-transcriptional manner by affecting the stability or translation of mRNAs and play important roles in many biological processes. Many microRNAs have been implicated in glioblastoma. miR-31 is dysregulated in several types of cancer including colon, breast, prostate, gastric and lung cancers. However, the expression and role of miR-31 in glioblastoma are still unclear. In this study, we performed real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays on 10 glioblastoma and 7 normal brain tissues. We found that miR-31 is down-regulated in glioblastoma compared with normal brain tissues. Ectopic expression of miR-31 inhibited migration and invasion ability of U251 glioma cells. Expression profiling analysis revealed that miR-31 affected the cell migration and motility process by regulating migration and invasion related genes. Finally, we demonstrated that miR-31 targeted radixin predominantly via inhibition of protein translation instead of degradation of mRNA. PMID- 22089332 TI - Gazing into the crystal ball; the future of computer-aided drug design. PMID- 22089333 TI - Investigation of charge-transfer complexes formation between photoluminescent graphene oxide and organic molecules. AB - Charge-transfer complexes have formed between photoluminescent graphene oxide and organic electron-donating molecules. With the increase of electron-donating power of molecules, the colour of solutions containing complexes became darker; UV absorption was red-shifted to longer wavelength and a new charge-transfer complex emission was also enhanced. PMID- 22089335 TI - Comparative-effectiveness research as it affects clinical pharmacology. PMID- 22089338 TI - Comparative efficacy and effectiveness: an opportunity for clinical pharmacology. AB - Over the past 10 or more years, the drug development paradigm has shifted radically as a consequence of the availability of generic formulations for many important drugs and the growing influence of major payers in controlling reimbursement of new medicines. The demand for health care in an aging and increasingly information-seeking population is steadily outstripping society's ability to pay for all possible treatments. Regulatory approval of new drugs is necessary but no longer sufficient for market access in many countries, including the United States. PMID- 22089339 TI - When should we believe nonrandomized studies of comparative effectiveness? AB - The demand for data from randomized comparative-effectiveness trials will always outstrip supply. Given their susceptibility to bias, several factors should be considered when examining nonrandomized comparative-effectiveness studies. These include comparability of treatments, magnitude of difference observed, sufficient attention to the underlying biology, examination of relationships supporting the main findings, whether the study includes only new users of the study treatments, whether the study end point is validly recorded, and replication of results. PMID- 22089340 TI - Model-based meta-analysis for comparative efficacy and safety: application in drug development and beyond. AB - High development cost, low development success, cost-disciplined health-care policies, and intense competition demand an efficient drug development process. New compounds need to bring value to patients by being safe, efficacious, and cost-effective as compared with existing treatment options. Model-based meta analysis (MBMA) facilitates integration and utilization of summary-level efficacy and safety data, providing a quantitative framework for comparative efficacy and safety assessment. This Commentary discusses the application and limitations of MBMA in drug development. PMID- 22089341 TI - Clearing the smoke around medical marijuana. AB - The hazy world of "medical marijuana" continues to cry out for clear data on which to base medical decision making and rational policy design. In this issue of Clinical Pharmacology & Therapeutics, Abrams and colleagues report that vaporized cannabis does not meaningfully affect opioid plasma levels and may even augment the efficacy of oxycodone and morphine in patients with chronic non cancer pain. This Commentary considers the implications of this work for clinical practice and further research initiatives. PMID- 22089342 TI - PON1 Q192R and clopidogrel: a case of the winner's curse or inadequate replication? AB - The antiplatelet drug clopidogrel is one of the most commonly prescribed drugs in the world, but there is wide interpatient variability in its antiplatelet effects. The majority of this variation is due to genetic effects, but there is controversy over which genetic variants are important and their relative contribution. This controversy may stem from the genetic association research paradigm, which casts the "winner's curse." PMID- 22089343 TI - Unveiling the mysteries of clopidogrel metabolism and efficacy. AB - Clopidogrel is an important antiplatelet agent, but a considerable variability in the biological effect of the drug has been observed. Additionally, patients with insufficient platelet reactivity inhibition following a loading dose (LD) of clopidogrel have a poor outcome. The mechanisms of variability are dependent on genetic polymorphisms of enzymes involved in clopidogrel metabolism. Paraoxonase 1 has been identified as the main determinant of the biological and clinical efficacy of clopidogrel. This finding could enable the use of pharmacogenomics to tailor antiplatelet agents. PMID- 22089345 TI - KRAS detection in colonic tumors by DNA extraction from FTA paper: the molecular touch-prep. AB - DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue is usually more degraded and contains more polymerase chain reaction (PCR) inhibitors than DNA isolated from nonfixed tissue. In addition, the tumor size and cellular heterogeneity found in tissue sections can often impact testing for molecular biomarkers. As a potential remedy to this situation, we evaluated the use of Whatman FTA paper cards for collection of colorectal tumor samples before tissue fixation and for isolation of DNA for use in a real-time PCR-based KRAS mutation assay. Eleven colon tumor samples were collected by making a cut into the fresh tumor and applying the Whatman FTA paper to the cut surface. Matched FFPE tissue blocks from these tumors were also collected for comparison. KRAS mutation analysis was carried out using the Applied Biosystems 7500 Fast Real-time PCR System using 7 independent custom TaqMan PCR assays. Of the 11 colon tumors sampled, 6 were positive for KRAS mutations in both the Whatman FTA paper preparations and corresponding FFPE samples. Whatman FTA paper cards for collection of colorectal tumor samples before tissue fixation and for isolation of DNA have many advantages including ease of use, intrinsic antimicrobial properties, long storage potential (stability of DNA over time), and a faster turnaround time for results. Extracted DNA should be suitable for most molecular diagnostic assays that use PCR techniques. This novel means of DNA preservation from surgical specimens would benefit from additional study and validation as a dependable and practical technique to preserve specimens for molecular testing. PMID- 22089346 TI - Analysis of hematopoietic stem cell transplant engraftment: use of loss or gain of microsatellite alleles to identify residual hematopoietic malignancy. AB - Polymorphic short tandem repeat (STR), or microsatellite, loci have been widely used to analyze chimerism status after allogeneic hematopoietic stem cell transplantation. The presence of a patient's DNA, as identified by STR analysis, may indicate residual or recurrent malignant disease or may represent normal hematopoiesis of patient origin. The ratio of patient-derived to donor-derived alleles is used to calculate the relative amount of patient cells (both benign and malignant) to donor cells. STRs on chromosomes known to be gained or lost in a patient's tumor are generally ignored because it is difficult to perform meaningful calculations of mixed chimerism. However, in this study, we present evidence that STR loci on gained or lost chromosomes are useful in distinguishing the benign or malignant nature of chimeric DNA. In the peripheral blood or bone marrow of 4 hematopoietic stem cell transplantation patients with leukemia or lymphoma, we identified tumor DNA on the basis of STR loci showing copy number alteration. We propose that a targeted evaluation of STR loci showing altered copy number in posttransplant chimerism analysis can provide evidence of residual cancer cells. PMID- 22089347 TI - Expression analysis on archival material: comparison of 5 commercially available RNA isolation kits for FFPE material. AB - BACKGROUND: Formalin-fixed paraffin-embedded (FFPE) tissue is the most common tissue specimen widely available. Moreover, long clinical follow-up is on hand. Therefore, FFPE material is a precious source of material for identifying predictive and/or prognostic biomarkers in cancer research on the basis of gene expression. However, the main drawback of FFPE tissue is the significant reduction in quantity and quality of the extracted RNA. The aim of this study is the comparison of different commercially available kits for the RNA isolation in FFPE tissue material. METHODS: Five commercially available RNA isolation kits were tested and the concentration, purity, integrity, and raw cycle threshold values were determined. RESULTS: The mean total RNA concentrations were as follows: Qiagen 25957+/-19417 ng, Ambion 8249+/-2898 ng, SA Biosciences 8070+/ 3700 ng, and Macherey-Nagel 622+/-394 ng. The mean A260/A280 ratios were as follows: Qiagen: 1.81, SA Biosciences: 0.66, Ambion: 1.03, and Macherey-Nagel: 1.04. The mean A260/A230 ratios were as follows: Qiagen: 1.88, SA Biosciences: 1.61, Ambion: 1.54, and Macherey-Nagel: 1.88. The RNA extractions from Epicentre could not be measured by the Nanodrop and, therefore, were excluded from further analysis. The mean RNA integrity number (range, 2.09 to 2.47) and the mean raw cycle threshold values (range, 33.43 to 35.37) were more or less the same for all the tested RNA isolation kits. CONCLUSIONS: Altogether, on the basis of the number of adequate isolations, the kit from Qiagen seems to be the most appropriate kit to be used in our further studies that require RNA isolation from FFPE material. PMID- 22089348 TI - Reference genes for gene expression analysis by real-time reverse transcription polymerase chain reaction of renal cell carcinoma. AB - BACKGROUND: Differentiation between malignant renal cell carcinoma and benign oncocytoma is of great importance to choose the optimal treatment. Accurate preoperative diagnosis of renal tumor is therefore crucial; however, existing imaging techniques and histologic examinations are incapable of providing an optimal differentiation profile. Analysis of gene expression of molecular markers is a new possibility but relies on appropriate standardization to compare different samples. The aim of this study was to identify stably expressed reference genes suitable for the normalization of results extracted from gene expression analysis of renal tumors. METHODS: Expression levels of 8 potential reference genes (ATP5J, HMBS, HPRT1, PPIA, TBP, 18S, GAPDH, and POLR2A) were examined by real-time reverse transcription polymerase chain reaction in tumor and normal tissue from removed kidneys from 13 patients with renal cell carcinoma and 5 patients with oncocytoma. RESULTS: The expression levels of genes were compared by gene stability value M, average gene stability M, pairwise variation V, and coefficient of variation CV. More candidates were not suitable for the purpose, but a combination of HMBS, PPIA, ATP5J, and TBP was found to be the best combination with an average gene stability value M of 0.9 and a CV of 0.4 in the 18 tumors and normal tissues. CONCLUSIONS: A combination of 4 genes, HMBS, PPIA, ATP5J, and TBP, is a possible reference in renal tumor gene expression analysis by reverse transcription polymerase chain reaction. A combination of four genes, HMBS, PPIA, ATP5J and TBP, being stably expressed in tissues from RCC is possible reference genes for gene expression analysis. PMID- 22089349 TI - DDIT3 gene break-apart as a molecular marker for diagnosis of myxoid liposarcoma- assay validation and clinical experience. AB - Myxoid liposarcoma with or without a round cell component is the most common subtype of liposarcoma. The diagnosis of myxoid liposarcoma could be challenging with histology, as a variety of soft tissue tumors with myxoid change might mimic myxoid liposarcoma, especially on small biopsy tissues. Chromosomal translocations of t(12,16) (q13;p11) and t(12;22) (q13;q12), rendering gene fusions of DDIT3 (previously CHOP) with FUS and EWSR1, have been found to be characteristic of myxoid liposarcoma, and were identifiable in more than 95% cases. These genetic alterations, therefore, are ideal as molecular markers to facilitate the diagnosis of this type of tumor. DDIT3 (12q13) dual-color break apart rearrangement probe for fluorescence in situ hybridization has been commercially available. However, its consistency with DDIT3-associated gene fusion and its clinical use, including sensitivity and specificity, have not been adequately evaluated. In this study, we assessed the locus specificity of the probe on metaphase, and then tested it on 8 cases of myxoid liposarcoma, 12 cases of other sarcomas, and 18 cases of tumors with myxoid differentiation. All 8 myxoid liposarcomas showed DDIT3 gene break-apart, whereas all 12 other sarcomas were negative. All the cases with DDIT3 break-apart also showed FUS-DDIT3 fusion by reverse transcription-polymerase chain reaction, with 100% consistency. In addition, the FISH assay has been clinically applied on 18 myxoid tumors with promising outcome. In conclusion, FISH with DDIT3 break-apart probe is a highly sensitive and specific assay for detection of DDIT3-associated gene fusions, and therefore is a valuable adjunct in diagnosis or differential diagnosis of myxoid liposarcoma. PMID- 22089350 TI - Characterization of molecular genetic alterations in GBMs highlights a distinctive molecular profile in young adults. AB - To evaluate age-related differences in histopathologic and molecular profile of glioblastomas (GBMs) at various age groups, with special reference to TP53 mutation, epidermal growth factor receptor (EGFR) amplification, EGFR vIII mutant, PTEN deletion, and IDH1 mutation. Agewise GBM incidence was calculated over a period of 5 years (2005 to 2009). Seventy-five GBMs were selected for molecular analysis. Majority of cases were in the age group of 41 to 60 years, and mean age was 43.6 years. Histology of all 75 cases selected for molecular profiling was identical. Primary adult GBMs showed EGFR amplification and PTEN deletion in majority (37.3% and 54.9%, respectively). TP53 and IDH1 mutations were rare (11.8% cases each). In secondary GBMs, TP53 (66.7%) and IDH1 mutations (44.4%) were most frequent. PTEN deletion was seen in 33.3% and none had EGFR amplification. Pediatric GBMs (<18 y) harbored frequent TP53 mutations (46.7%) and PTEN deletion in 40%. IDH1 mutations and EGFR amplification were absent. The molecular profile of primary GBMs in young adults (19 to 40 y) was distinctly different from that of adults older than 40 years. TP53 mutation was present in 20% cases. The frequency of EGFR amplification (13.3%) and PTEN deletion (33.3%) was significantly low (P=0.028 and 0.046, respectively). IDH1 mutation, which is rare in primary adult GBMs, was present in 40% of cases. Molecular heterogeneity exists within GBMs of different age cohorts. The molecular profile of GBMs in young adults is distinctly different. Thus, there is a strong need for further studies in various age groups to provide guidelines for therapeutic targeting. PMID- 22089351 TI - Galectin-3 and CD44v6 as markers for preoperative diagnosis of thyroid cancer by RT-PCR. AB - The aim of the study was to determine the diagnostic value of reverse transcriptase polymerase chain reaction (RT-PCR) analysis of galectin-3 and CD44v6 as markers for preoperative diagnosis of malignancy in lesions of the thyroid. RT-PCR analysis of galectin-3 and CD44v6 expression was performed on RNA isolated from fine-needle aspirates of thyroid lesions from 428 patients. The results were evaluated against the postoperative histopathological diagnosis or definitive cytological diagnosis in cases of nodular goiter and Hashimoto thyroiditis. A total of 57 (13%) samples were inadequate for RT-PCR. Galectin-3 and CD44v6 were positive in 167 (45%) and 158 (43%) out of 371 adequate samples, respectively. Galectin-3 and CD44v6 were positive in 56 (86%) and 54 (83%) out of 65 papillary carcinomas, in 16 (29%) and 18 (32%) out of 56 Hashimoto's thyroiditis, in 61 (34%) and 52 (29%) out of 181 nodular goiters, in 23 (43%) and 23 (43%) out of 53 follicular adenomas, in 3 (100%) and 3 (100%) out of 3 follicular carcinomas, and in 8 (62%) and 8 (62%) out of 13 Hurthle cell adenomas, respectively. Specificity, sensitivity, and positive and negative predictive values in discriminating between malignant and benign thyroid nodules were 64, 87, and 35 and 96% for galectin-3; 67, 84, and 36 and 95% for CD44v6; and 79, 82, and 47 and 95% for the analysis of both markers (considered positive only if both galectin-3 and CD44v6 were positive), respectively. Owing to relatively low specificity, the clinical value of galectin-3 and CD44v6 analysis by RT-PCR as a marker for preoperative diagnosis of malignancy in thyroid lesions is limited. PMID- 22089352 TI - Establishment of a novel target-based real-time quantitative PCR method for Acinetobacter baumannii detection. AB - Biofilm formation is a well-known pathogenic mechanism in infections caused by Acinetobacter baumannii. Recently, a biofilm synthesis-associated gene has been found in A. baumannii ATCC19606. Bioinformatic analysis showed 2 transmembrane structures and an hmsS superfamily domain, which was related to biofilm formation. What is more, high homology sequences of the bfs gene were only present in A. baumannii spp., and the similarities of nucleotide sequences of the bfs gene from A. baumannii strains ATCC17978, ACICU, S1, AB307-0294, and AB0057 compared with the reported sequence of bfs (GenBank accession No.: NZ_GG704572) were all above 95%. The distribution and conservation of the bfs gene from clinically derived A. baumannii strains were verified through conventional polymerase chain reaction (PCR). After this, we established a bfs gene-based real time quantitative PCR assay to detect A. baumannii. Species specificity and sensitivity assays were designed and validated. By using this method, all the A. baumannii strains separated from clinical samples were identified and showed good accordance with the results from biochemical identification. This study is the first report of developing a bfs gene-based quantitative polymerase chain reaction for rapid, stable, and specific detection of A. baumannii. This method can be applied to clinical laboratory diagnosis, and detection of A. baumannii present on medical instruments. PMID- 22089353 TI - Timely diagnosis and disclosure of Alzheimer disease gives patients opportunities to make choices. PMID- 22089354 TI - Dermatologists' awareness of and screening practices for hepatitis B virus infection before initiating tumor necrosis factor-alpha inhibitor therapy. AB - OBJECTIVE: The aim of the study was to assess dermatologists' awareness of available guidelines and drug package insert information on the screening for and management of hepatitis B (HBV) infection in patients receiving tumor necrosis factor-alpha inhibitor (TNF-alphaI) drug therapies for dermatological disorders. MATERIALS AND METHODS: An electronic descriptive cross-sectional questionnaire was administered to a random, nationwide sample of physician members of the American Academy of Dermatology. Each participating physician answered 8 questions regarding his or her awareness of the risk of HBV reactivation. RESULTS: More than half of the dermatologists surveyed (52%) were aware of guidelines regarding TNF-alphaI use in dermatological disorders. Dermatologists who were aware of the guidelines performed universal screening 81% of the time versus 3% of those who were unaware. Approximately 30% of the dermatologists were aware of drug manufacturers' package insert warnings for risk of HBV reactivation with TNF-alphaIs. Screening in their high-risk patients was highly variable because >90% performed screening in patients with a history of hepatitis or with elevated liver-associated enzymes. Most (73%) screened appropriately with HB surface antigen. One case of HBV reactivation was observed with infliximab use for psoriasis treatment. CONCLUSIONS: Based on this survey, improving education among dermatologists regarding the risks of HBV reactivation and its prevention for patients receiving TNF-alphaI seems warranted. More specific consensus guidelines are recommended to achieve universal screening as the standard of care in these patients. PMID- 22089355 TI - Risk factors of cellulitis treatment failure with once-daily intravenous cefazolin plus oral probenecid. AB - OBJECTIVES: Once-daily intravenous cefazolin with probenecid is used commonly to treat cellulitis. The primary objective of this study was to determine the risk factors of treatment failure with this regimen. METHODS: This was a retrospective cohort study of adult outpatients with cellulitis who were initially treated with once-daily intravenous cefazolin plus probenecid. Treatment failure is defined as inadequate improvement that necessitates either hospital admission or a change in antibiotic therapy to a different intravenous regimen. A stepwise logistic regression analysis was performed to determine the risk factors for regimen failure. RESULTS: From January 2003 to December 2008, 159 patients with cellulitis were initially treated with once daily intravenous cefazolin plus probenecid. Thirty-five (22%) patients had treatment failure. The treatment for 53% (9/17) of the patients with a history of chronic venous disease (CVD) failed, whereas the treatment for 18% (26/142) of patients without CVD failed (P = 0.001). Multivariate analysis identified the presence of CVD as the only risk factor associated with treatment failure (odds ratio 4.4, 95% confidence interval 1.5-13; P = .007). CONCLUSIONS: Patients with cellulitis and CVD who are being treated with once-daily intravenous cefazolin plus probenecid should be monitored closely for treatment failure. PMID- 22089356 TI - Differences in national antiretroviral prescribing patterns between black and white patients with HIV/AIDS, 1996-2006. AB - OBJECTIVES: The benefit of improved health outcomes for blacks receiving highly active antiretroviral therapy (HAART) lags behind that of whites. This project therefore sought to determine whether the reason for this discrepancy in health outcomes could be attributed to disparities in use of antiretroviral therapy between black and white patients with HIV. MATERIALS AND METHODS: The 1996-2006 National Hospital Ambulatory Medical Care Surveys were used to identify hospital outpatient visits that documented antiretrovirals. Patients younger than 18 years, of nonblack or nonwhite race, and lacking documentation of antiretrovirals were excluded. A multivariable logistic regression model was constructed with race as the independent variable and use of HAART as the dependent variable. RESULTS: Approximately 3 million HIV/AIDS patient visits were evaluated. Blacks were less likely than whites to use HAART and protease inhibitors (odds ratio, 95% CI 0.81 [0.81-0.82] and 0.67 [0.67-0.68], respectively). More blacks than whites used non-nucleoside reverse transcriptase inhibitors (odds ratio, 95% CI 1.18 [1.17-1.18]). In 1996, the crude rates of HAART were relatively low for both black and white cohorts (5% vs 6%). The rise in HAART for blacks appeared to lag behind that of whites for several years, until 2002, when the proportion of blacks receiving HAART slightly exceeded the proportion of whites receiving HAART. In later years, the rates of HAART were similar for blacks and whites (81% vs 82% in 2006). Blacks appeared less likely than whites to use protease inhibitors and more likely than whites to use non-nucleoside reverse transcriptase inhibitors from 2000 to 2004. CONCLUSIONS: Blacks experienced a lag in the use of antiretrovirals at the beginning of the study; this discrepancy dissipated in more recent years. PMID- 22089357 TI - HIV-related disparities: it is not all about HAART accessibility. PMID- 22089358 TI - Prevalence of atherosclerotic plaque in young and middle-aged asymptomatic individuals: the Bogalusa heart study. AB - OBJECTIVES: To determine the prevalence of carotid and femoral artery atherosclerotic plaque in a community-based population of asymptomatic African American and white men and women, with an age range of 29 to 51 years, and the potential relations with cardiovascular risk factors. METHODS: Between 2007 and 2010, 914 subjects, 58% women and 69% white, who were part of the Bogalusa Heart Study, an ongoing study of a southern biracial community in Bogalusa, Louisiana, were followed up from childhood through adulthood and assessed for plaque formation using ultrasound. Of the total number of subjects, those with a history of cardiovascular/cerebrovascular events were excluded. RESULTS: Plaque prevalence ranged from 8% to 14%, with greater frequency in white men. Plaque formation was also associated with smoking, hypertension, diabetes mellitus, age, and white race, in descending order. CONCLUSIONS: In this population, studied sequentially since 1973, the presence of plaque correlated with widely recognized cardiovascular risk factors, although we did not detect significant contributions from either obesity or elevated lipids, including low-density lipoprotein cholesterol. It is possible that interventions, such as diet alteration and statin therapy, may have a positive impact on these potential contributors to plaque formation, and hypertension, diabetes mellitus and smoking remain of great importance. PMID- 22089359 TI - Atherosclerosis--challenging the assumptions. PMID- 22089360 TI - Prevalence of colorectal cancer screening among a multimorbid rural Appalachian population. AB - OBJECTIVES: The purpose of this study was to determine the relation among multiple morbidities and the prevalence of colorectal cancer (CRC) screening among older adult Appalachian residents of Kentucky. This is the first known study to address multiple morbidities exclusively with a health-disparities population. METHODS: This was a cross-sectional study of 1153 subjects, aged 50 to 76 years, from Appalachian Kentucky. RESULTS: White race, post-high school education, and perception of having more than enough income on which to survive were associated with higher rates of any guideline concordant CRC screening. Statistically significant trends in the outcome of adjusted odds ratios for colonoscopy with greater number of morbidities (P < 0.05) were noted; the higher number of morbidities, the higher rates of screening. CONCLUSIONS: Contrary to much existing research, within a health-disparities population, we found a dose response relation between comorbidities and greater likelihood of CRC screening. Future research in this area should focus on explanations for this seldom described finding. In addition, this finding has meaningful clinical and behavioral implications, including ensuring provider screening recommendation during routine office visits and outreach, perhaps through community clinics and public health departments, to extremely vulnerable populations lacking access to preventive care. PMID- 22089361 TI - Factors associated with recently transmitted Mycobacterium tuberculosis strain MS0006 in Hinds County, Mississippi. AB - OBJECTIVE: The objective of this study was to investigate risk factors associated with tuberculosis (TB) transmission that was caused by Mycobacterium tuberculosis strain MS0006 from 2004 to 2009 in Hinds County, Mississippi. METHODS: DNA fingerprinting using spoligotyping, mycobacterial interspersed repetitive unit, and IS6110-based restriction fragment length polymorphism of culture-confirmed cases of TB was performed. Clinical and demographic factors associated with strain MS0006 were analyzed by univariate and multivariate analysis. RESULTS: Of the 144 cases of TB diagnosed during the study period, 117 were culture positive with fingerprints available. There were 48 different strains, of which 6 clustered strains were distributed among 74 patients. The MS0006 strain accounted for 46.2% of all culture-confirmed cases. Risk factors for having the MS0006 strain in a univariate analysis included homelessness, HIV co-infection, sputum smear negativity, tuberculin skin test negativity, and noninjectable drug use. Multivariate analysis identified homelessness (odds ratio 7.88, 95% confidence interval 2.90-21.35) and African American race (odds ratio 5.80, 95% confidence interval 1.37-24.55) as independent predictors of having TB caused by the MS0006 strain of M. tuberculosis. CONCLUSIONS: Our findings suggest that a majority of recently transmitted TB in the studied county was caused by the MS0006 strain. African American race and homelessness were significant risk factors for inclusion in the cluster. Molecular epidemiology techniques continue to provide in-depth analysis of disease transmission and play a vital role in effective contact tracing and interruption of ongoing transmission. PMID- 22089362 TI - Neonates at risk for congenital syphilis: radiographic and cerebrospinal fluid evaluations. AB - OBJECTIVE: To review the infants at risk for congenital syphilis (CS) and determine the optimal use of evaluations such as cerebrospinal fluid (CSF), the venereal disease research laboratory (VDRL) test, and long bone radiography studies. METHODS: A retrospective chart review of all of the infants at risk for CS from January 1997 to December 2002 at the Regional Medical Center at Memphis was conducted. Subjects were identified from a database of prenatal maternal records. Infant charts showing a diagnosis of presumptive CS were reviewed and data were collected. RESULTS: Of the 24,245 deliveries, maternal serology (rapid plasma reagin and microhemagglutination for treponemal antibody) was reactive in 250 women during pregnancy. Of 92 infants with a presumptive diagnosis of syphilis, only 2 (2.1%) were symptomatic. CSF examination for VDRL was feasible in 74 (80%) of the 92 infants. Only 1 (1.35%) of the 74 infants had a positive CSF-VDRL. Three infants had radiographic changes that were consistent with CS. CONCLUSIONS: The burden of syphilis in pregnancy remains high. Proper evaluation of neonates is important in preventing long-term consequences. The frequency of positive CSF and long bone radiography studies remains low. These evaluations should be made based on the symptoms and plan of treatment for individual neonates. PMID- 22089363 TI - Physical activity benefits and risks on the gastrointestinal system. AB - This review evaluates the current understanding of the benefits and risks of physical activity and exercise on the gastrointestinal system. A significant portion of endurance athletes are affected by gastrointestinal symptoms, but most symptoms are transient and do not have long-term consequences. Conversely, physical activity may have a protective effect on the gastrointestinal system. There is convincing evidence that physical activity reduces the risk of colon cancer. The evidence is less convincing for gastric and pancreatic cancers, gastroesophageal reflux disease, peptic ulcer disease, nonalcoholic fatty liver disease, cholelithiasis, diverticular disease, irritable bowel syndrome, and constipation. Physical activity may reduce the risk of gastrointestinal bleeding and inflammatory bowel disease, although this has not been proven unequivocally. This article provides a critical review of the evidence-based literature concerning exercise and physical activity effects on the gastrointestinal system and provides physicians with a better understanding of the evidence behind exercise prescriptions for patients with gastrointestinal disorders. Well designed prospective randomized trials evaluating the risks and benefits of exercise and physical activity on gastrointestinal disorders are recommended for future research. PMID- 22089364 TI - Benefits and risks of exercise on the gastrointestinal system. PMID- 22089365 TI - Follow-up study of a pregnant woman 16 years after exposure in the Xinzhou radiation accident. AB - To investigate the late effects of radiation on child-bearing women, a follow-up study was performed on a 39-year-old survivor 16 years after a (60)Co radiation accident. The woman, Fang, was 19 weeks pregnant at the time of exposure. Physical examinations, a full range of clinical laboratory and imaging tests, as well as cytogenetic analyses were conducted to evaluate Fang's current health conditions. Fang shows the appearance of premature ageing and has a decreased menstrual period. Laboratory studies and imaging tests suggest nodular goitre disease and osteoporosis. Otherwise, no apparent abnormalities were found in the major organs. No malignant tumours were detected by either tumour markers or imaging tests. However, the existence of chromosome aberrations warrants long term follow-up for tumour incidence in the future. Fang became pregnant 8 years after the accident, but suffered a miscarriage due to the death of the foetus at 6 months into the pregnancy. In conclusion, our findings suggest that the intrauterine death of the foetus might be associated with the previous exposure. There is no evidence of malignant tumours as of the date of the follow-up study. Non-cancerous diseases, i.e. thyroid disease and osteoporosis, which may be related to radiation exposure, are the major manifestations of the long-term effects of the accident. PMID- 22089366 TI - RETRACTED ARTICLE: Acute and chronic toxicity of the pharmaceutical levonorgestrel to the freshwater crustacean Daphnia magna. PMID- 22089367 TI - Analysis of the predicting variables for daily and weekly fluctuations of two airborne fungal spores: Alternaria and Cladosporium. AB - Alternaria and Cladosporium are two fungal taxa whose spores (conidia) are included frequently in aerobiological studies of outdoor environments. Both spore types are present in the atmosphere of Malaga (Spain) throughout almost the entire year, although they reach their highest concentrations during spring and autumn. To establish predicting variables for daily and weekly fluctuations, Spearman's correlations and stepwise multiple regressions between spore concentrations (measured using a volumetric 7-day recorder) and meteorological variables were made with results obtained for both spore types in 1996 and 1997. Correlations and regressions were also made between the different taxa and their concentrations in different years. Significant and positive correlation coefficients were always obtained between spore concentrations of both taxa, followed by temperature, their concentrations in different years, sunshine hours and relative humidity (this last in a negative sense). For the two spore types we obtained higher correlation and regression coefficients using weekly data. We showed different regression models using weekly values. From the results and a practical point of view, it was concluded that weekly values of the atmospheric concentration of Alternaria spores can be predicted from the maximum temperature expected and its concentrations in the years sampled. As regards the atmospheric concentration of Cladoposrium spores, the weekly values can be predicted based on the concentration of Alternaria spores, thus saving the time and effort that would otherwise be employed in counting them by optical microscopy. PMID- 22089368 TI - Surgical intervention strategies for pediatric ovarian tumors: experience with 60 cases at one institution. AB - PURPOSE: The aim of this study was to assess the surgical intervention strategies for pediatric ovarian tumors. METHODS: The clinical features and treatment were analyzed for 60 children with ovarian tumors treated at our institution between 2000 and 2010. RESULTS: Twenty-one of the 60 patients were prenatally diagnosed neonatal cases with cystic lesions. Of the 21 neonates, surgery included ultrasound-guided aspiration in 14 cases, salpingo-oophorectomy by umbilical crease incision in 6 cases with torsions, and cystectomy with ovarian preservation in one case with torsion. The mean age of the other 39 patients was 9.3 years. For 31 of these patients with benign lesions, surgery included tumor resection with ovarian preservation after aspiration of the cystic lesion through a modified Rocky Davis incision in 21 cases containing 3 torsion cases, and salpingo-oophorectomy in 10 cases, including 8 torsion cases. A salpingo oophorectomy was performed for all eight of the patients with malignant tumors, including borderline lesions of mucinous or serous cyst adenoma, and postoperative chemotherapy was administered for two yolk sac tumors and one dysgerminoma. Only one case demonstrating a yolk sac tumor with lung metastasis at initial diagnosis died of disease after recurrence. CONCLUSIONS: The majority of pediatric ovarian tumors were benign disease, and the patients with malignant lesions had a good prognosis. In neonatal cases, an umbilical crease incision approach is feasible and provides excellent cosmesis. We recommend tumor resection with ovarian preservation through a minimally invasive approach (modified Rocky Davis incision) as the first line treatment for older pediatric patients with ovarian tumors other than those preoperatively diagnosed as malignant. PMID- 22089369 TI - Preparation of organic-inorganic hybrid Fe-MoO(x)/polyaniline nanorods as efficient catalysts for alkene epoxidation. AB - Novel Fe-MoO(x)/polyaniline nanorods were fabricated via in situ polymerization of Mo(3)O(10)(C(6)H(5)NH(3))(2).2H(2)O nanowires, in which interface reactions remarkably influenced the morphology of products; and the nanorods showed high performance in cyclooctene epoxidation due to the organic-inorganic hybrid structure and Fe(3+) additive. PMID- 22089370 TI - Nanodiamond for hydrogen storage: temperature-dependent hydrogenation and charge induced dehydrogenation. AB - Carbon-based hydrogen storage materials are one of hottest research topics in materials science. Although the majority of studies focus on highly porous loosely bound systems, these systems have various limitations including use at elevated temperature. Here we propose, based on computer simulations, that diamond nanoparticles may provide a new promising high temperature candidate with a moderate storage capacity, but good potential for recyclability. The hydrogenation of nanodiamonds is found to be easily achieved, in agreement with experiments, though we find the stability of hydrogenation is dependent on the morphology of nanodiamonds and surrounding environment. Hydrogenation is thermodynamically favourable even at high temperature in pure hydrogen, ammonia, and methane gas reservoirs, whereas water vapour can help to reduce the energy barrier for desorption. The greatest challenge in using this material is the breaking of the strong covalent C-H bonds, and we have identified that the spontaneous release of atomic hydrogen may be achieved through charging of hydrogenated nanodiamonds. If the degree of induced charge is properly controlled, the integrity of the host nanodiamond is maintained, which indicates that an efficient and recyclable approach for hydrogen release may be possible. PMID- 22089371 TI - Accuracy and inter-observer reliability of visual estimation compared to clinical goniometry of the elbow. AB - PURPOSE: To test the hypothesis that visual estimation by a trained observer is as accurate and reliable as clinical goniometry for measuring elbow range of motion. METHODS: Instrument validity and inter-observer reliability of visual estimation was evaluated on a consecutive series of 50 elbow contractures. Four observers with different levels of elbow experience first estimated extension and flexion of the contracted elbows and then measured them with a blinded goniometer. RESULTS: Instrument validity for visually-based goniometry was extremely high. ICC scores were 0.97 for both extension and flexion estimations. Systematic error was negligible (1 degrees ) with upper limits of agreement being 9 degrees (95% CI: 7 degrees -11 degrees ) and 8 degrees (95% CI: 6 degrees -10 degrees ), respectively, for extension and flexion. For the expert surgeon, 92% of the visual estimates were within 5 degrees of the value obtained by clinical goniometry. Between experienced observers (elbow surgeon and physician assistant), the ICC's were very high-0.96 for extension and 0.93 for flexion. The systematic errors were low, from -1 degrees to 1 degrees with upper limit of agreement being 11 degrees (95% CI: 8 degrees -14 degrees ). However, agreement was poor between an inexperienced study coordinator and the others (ICC's: 0.51 0.38, systematic errors: 8 degrees -18 degrees , upper limit of agreement: 32 degrees -40 degrees ). The accuracy of the visual estimations made by the experienced elbow surgeon was as good as the measurements taken with a goniometer by the physician assistant or the clinical fellow and better than those taken by an inexperienced study coordinator. CONCLUSIONS: The trained human eye is highly capable of accurately estimating the range of motion of the elbow, compared to conventional clinical goniometry, depending on the experience of the observer. LEVEL OF EVIDENCE: Diagnostic study, Level II. PMID- 22089372 TI - Increased BMP expression in arthrofibrosis after TKA. AB - PURPOSE: Because of the multiple possible aetiologies of painful total knee arthroplasty (TKA), the diagnosis and treatment of such patients are challenging. In a considerable number of patients, an intraarticular pathology is present, although not verifiable with clinical and diagnostic imaging techniques as in cases of primary arthrofibrosis. In these patients, the differentiation between intra- and extraarticular causes of pain remains difficult. Until now, little attention has been paid to changes of the synovial fluid and tissue in these knees. The objective of this study was to analyse the changes of the synovial environment in patients suffering from arthrofibrosis after TKA in comparison with knees with referred pain suffering from hip arthritis. The changes of the synovial environment probably provide additional diagnostic information to verify an intraarticular pathology. METHODS: The synovial fluid of 10 consecutive knees in 10 patients presenting with a primary arthrofibrosis after TKA without signs of infection, instability, malalignment, or loosening was analysed and compared to the synovial fluid of 10 knees with referred pain serving as controls. The BMP 2 concentration was measured in the synovial fluid, and the presence of cytokines leading to an overexpression of BMP-2 was detected by measuring the change of BMP 2 expression in a synoviocyte cell line following exposing to the synovial fluid of the patients. RESULTS: The concentration of BMP-2 in the synovial fluid was significantly higher in arthrofibrotic TKA knees (24.3 +/- 6.9 pg/mL), compared with the control group 5.9 +/- 4.8 pg/mL (P < 0.001). Corresponding to this finding, BMP-2 expression in synoviocytes was upregulated 11.5-fold (P < 0.05) by synovial fluid of patients suffering from arthrofibrosis after TKA, compared with the control group with referred pain. CONCLUSION: BMP-2 is overexpressed and its concentrations are consequently higher in patients suffering from arthrofibrosis after TKA. The synovial BMP-2 concentration may be a potential marker for differentiating between intra- and extraarticular causes of pain. LEVEL OF EVIDENCE: II. PMID- 22089373 TI - The safety and short-term efficacy of a novel polyurethane meniscal scaffold for the treatment of segmental medial meniscus deficiency. AB - PURPOSE: Meniscal loss is associated with an increased risk of developing osteoarthritis. Tissue engineering solutions, which include the development of novel material scaffolds, are being utilised to aid the regeneration of meniscal tissue. The purpose of this study was to monitor the safety profile and the short term efficacy of a novel polyurethane meniscal scaffold in the treatment of patients with painful knees following partial medial meniscectomy. METHODS: Ten consecutive patients with segmental tissue loss from the medial meniscus were treated with the arthroscopic implantation of an Actifit((r)) (Orteq Sports Medicine) polyurethane meniscal scaffold. Patients were followed up at 2 and 6 weeks, then again at 6 and 12 months. Primary outcome measures included reporting of complications and patient-reported outcome scores (KOOS, KSS, UCLA Activity scale, VAS pain). Secondary outcome was MRI assessment at 6 and 12 months looking at scaffold morphology, integration and associated joint injury/inflammation. RESULTS: Eight male and 2 female patients were included in the study with a mean age of 29 (range 18-45). No complications were reported. All patients were happy with their surgery. At 6 months, a statistically significant improvement (P < 0.05) in all PROMS except the UCLA activity scale and VAS pain scale were noted. The improvement remained at 12 months. MRI analysis revealed the presence of scaffolds at 6 months, with evidence of some tissue integration in many improvements in scaffold morphology and ICRS classification of cartilage in the medial compartment were noted at 12 months. No synovitis was noted in the joint or adverse reactions in the other compartments. CONCLUSION: The new Actifit((r)) polyurethane scaffold has been shown to be a safe, effective implant, for the treatment of patients with pain as a result of segmental medial meniscus loss at 1 year. LEVEL OF EVIDENCE: IV. PMID- 22089374 TI - Projected life expectancy of people with HIV according to timing of diagnosis. AB - BACKGROUND AND OBJECTIVES: Effective antiretroviral therapy (ART) has contributed greatly toward survival for people with HIV, yet many remain undiagnosed until very late. Our aims were to estimate the life expectancy of an HIV-infected MSM living in a developed country with extensive access to ART and healthcare, and to assess the effect of late diagnosis on life expectancy. METHODS: A stochastic computer simulation model of HIV infection and the effect of ART was used to estimate life expectancy and determine the distribution of potential lifetime outcomes of an MSM, aged 30 years, who becomes HIV positive in 2010. The effect of altering the diagnosis rate was investigated. RESULTS: Assuming a high rate of HIV diagnosis (median CD4 cell count at diagnosis, 432 cells/MUl), projected median age at death (life expectancy) was 75.0 years. This implies 7.0 years of life were lost on average due to HIV. Cumulative risks of death by 5 and 10 years after infection were 2.3 and 5.2%, respectively. The 95% uncertainty bound for life expectancy was (68.0,77.3) years. When a low diagnosis rate was assumed (diagnosis only when symptomatic, median CD4 cell count 140 cells/MUl), life expectancy was 71.5 years, implying an average 10.5 years of life lost due to HIV. CONCLUSION: If low rates of virologic failure observed in treated patients continue, predicted life expectancy is relatively high in people with HIV who can access a wide range of antiretrovirals. The greatest risk of excess mortality is due to delays in HIV diagnosis. PMID- 22089375 TI - Mental health disorders and the risk of AIDS-defining illness and death in HIV infected veterans. AB - OBJECTIVE: Mental health comorbidities are common in HIV-infected veterans and can impact clinical outcomes for HIV. We examined the impact of mental health diagnoses on progression to AIDS-defining illness (ADI) and death in a large cohort of HIV-infected veterans who accessed care between 2001 and 2006. DESIGN: Retrospective cohort study using the national Veterans Health Administration (VHA) HIV Clinical Case Registry. METHODS: We identified HIV-infected veterans initiating combination antiretroviral therapy (cART) within the VHA between 2000 and 2006. The prevalences of the following mental health diagnoses were examined: schizophrenia, bipolar disorder, depression, anxiety, and substance use disorder. Cox proportional hazards models were constructed to examine the relationship between mental health conditions and two outcomes, all-cause mortality and ADI. Models were computed before and after adjusting for confounding factors including age, race, baseline CD4 cell count, comorbidities and cART adherence. RESULTS: Among 9003 veterans receiving cART, 31% had no mental health diagnosis. Age, race, baseline comorbidity score, CD4, and cART adherence were associated with shorter time to ADI or death. All-cause mortality was more likely among veterans with schizophrenia, bipolar disorder and substance use, and ADI was more likely to occur among veterans with substance use disorder. CONCLUSIONS: Our results demonstrate the high prevalence of mental health diagnoses among HIV-infected veterans. In the era of highly active antiretroviral therapy, presence of psychiatric diagnoses impacted survival and development of ADI. More aggressive measures addressing substance abuse and severe mental illness in HIV-infected veterans are necessary. PMID- 22089376 TI - The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring. AB - OBJECTIVES: We examined the effect of switching to second-line antiretroviral therapy (ART) on mortality in patients who experienced immunological failure in ART programmes without access to routine viral load monitoring in sub-Saharan Africa. DESIGN AND SETTING: Collaborative analysis of two ART programmes in Lusaka, Zambia and Lilongwe, Malawi. METHODS: We included all adult patients experiencing immunological failure based on WHO criteria. We used Cox proportional hazards models weighted by the inverse probability of switching to compare mortality between patients who switched and patients who did not; and between patients who switched immediately and patients who switched later. Results are expressed as hazard ratios with 95% credible intervals (95% CI). RESULTS: Among 2411 patients with immunological failure 324 patients (13.4%) switched to second-line ART during 3932 person-years of follow-up. The median CD4 cell count at start of ART and failure was lower in patients who switched compared to patients who did not: 80 versus 155 cells/MUl (P < 0.001) and 77 versus 146 cells/MUl (P < 0.001), respectively. Adjusting for baseline and time dependent confounders, mortality was lower among patients who switched compared to patients remaining on failing first-line ART: hazard ratio 0.25 (95% CI 0.09 0.72). Mortality was also lower among patients who remained on failing first-line ART for shorter periods: hazard ratio 0.70 (95% CI 0.44-1.09) per 6 months shorter exposure. CONCLUSION: In ART programmes switching patients to second-line regimens based on WHO immunological failure criteria appears to reduce mortality, with the greatest benefit in patients switching immediately after immunological failure is diagnosed. PMID- 22089378 TI - Cost-effectiveness of combination therapy with etravirine in treatment experienced adults with HIV-1 infection. AB - OBJECTIVE: To assess the cost-effectiveness of etravirine (INTELENCE), a novel nonnucleoside reverse transcriptase inhibitor, used in combination with a background regimen that included darunavir/ritonavir, from a Canadian Provincial Ministry of Health perspective. DESIGN: A Markov model with a 3-month cycle time and six health states based on CD4 cell count ranges was developed to follow a hypothetical cohort of treatment-experienced adults with HIV-1 infection through initial and subsequent treatment regimens. METHODS: Costs (in 2009 Canadian dollars), utilities, and HIV-related mortality data for each health state as well as non-HIV-related mortality data were estimated from Canadian sources and published literature. Transition probabilities between health states and first year hospitalization and mortality rates were derived from clinical trial data. Incremental 1-year costs per additional adult with viral load less than 50 copies/ml at 48 weeks and incremental lifetime costs per quality-adjusted life year (QALY) gained were estimated using a 5% discount rate. Sensitivity and variability analyses and model validation were performed. RESULTS: Etravirine was associated with an increased probability of achieving less than 50 copies/ml at 48 weeks of 0.205 and an estimated gain of 0.66 discounted (1.48 undiscounted) QALYs over a lifetime. The incremental 1-year cost per additional person with viral load less than 50 copies/ml was $23,862. The lifetime incremental cost per QALY gained was $49,120. For the uncertainty ranges and variability scenarios tested for the lifetime horizon, the cost-effectiveness ratio was between $28,859 and 66,249. CONCLUSION: When compared with optimized standard of care including darunavir/ritonavir, adding etravirine represents a cost-effective option for treatment-experienced adults in Canada. PMID- 22089377 TI - Ten-year diabetes incidence in 1046 HIV-infected patients started on a combination antiretroviral treatment. AB - OBJECTIVE: To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009. DESIGN: Prospective study of 1046 patients at 47 French clinical sites. METHODS: Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure. RESULTS: Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when >=50 years), overweight (hazard ratio = 1.91 for a BMI 25-29 kg/m(2), hazard ratio = 2.85 >30 kg/m(2)), waist-to hip ratio (hazard ratio = 3.87 for >=0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes. CONCLUSIONS: In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients. PMID- 22089379 TI - Effect of raltegravir intensification on HIV proviral DNA in the blood and gut mucosa of men on long-term therapy: a randomized controlled trial. AB - BACKGROUND: Highly active antiretroviral therapy (HAART) dramatically reduces plasma HIV-1 viremia. However, despite completely suppressive HAART, it has been suggested that low-levels of viral replication may persist in the gut mucosa and elsewhere in individuals on long-term HAART. OBJECTIVE: We conducted a double blind randomized, placebo-controlled trial evaluating whether intensification of HAART in long-term virologically suppressed individuals with raltegravir is associated with a reduction in the level of proviral HIV-1 DNA in CD4(+) T cells in blood and the sigmoid colon (gut). METHODS: Long-term (>4 years) virologically suppressed HIV-infected individuals on standard HAART were randomized 1 : 1 in a double-blind fashion to receive raltegravir (400 mg twice/day) or placebo for 48 weeks. After week 48, all participants were treated with raltegravir to week 96. Blood and sigmoid biopsies were sampled and the frequency of CD4(+) T cells carrying HIV-1 proviral DNA was determined. RESULTS: Twenty-four study patients were recruited. At 48 weeks, no difference was apparent between participants receiving raltegravir or placebo in blood HIV-1 proviral levels (P = 0.62), CD4(+) T-cell counts (P = 0.25) and gut proviral loads (P = 0.74). Similarly, prolonged raltegravir intensification up to week 96 had no further effect on both blood and gut HIV-1 proviral loads and blood CD4(+) T-cell counts. CONCLUSION: In long-term virologically suppressed patients on standard HAART, intensification with raltegravir did not result in further decay of CD4(+) T cells carrying HIV-1 proviral DNA in either the blood or gut after 48 or 96 weeks of therapy, or in any increase in CD4(+) T-cell counts. PMID- 22089380 TI - Prevalence of seroconversion symptoms and relationship to set-point viral load: findings from a subtype C epidemic, 1995-2009. AB - OBJECTIVE: To describe symptoms, physical examination findings, and set-point viral load associated with acute HIV seroconversion in a heterosexual cohort of HIV-discordant couples in Zambia. DESIGN: We followed HIV serodiscordant couples in Lusaka, Zambia from 1995 to 2009 with HIV testing of negative partners and symptom inventories 3 monthly, and physical examinations annually. METHODS: We compared prevalence of self-reported or treated symptoms (malaria syndrome, chronic diarrhea, asthenia, night sweats, and oral candidiasis) and annual physical examination findings (unilateral or bilateral neck, axillary, or inguinal adenopathy; and dermatosis) in seroconverting vs. HIV-negative or HIV positive intervals, controlling for repeated observations, age, and sex. A composite score comprised of significant symptoms and physical examination findings predictive of seroconversion vs. HIV-negative intervals was constructed. We modeled the relationship between number of symptoms and physical examination findings at seroconversion and log set-point viral load using linear regression. RESULTS: Two thousand, three hundred and eighty-eight HIV-negative partners were followed for a median of 18 months; 429 seroconversions occurred. Neither symptoms nor physical examination findings were reported for most seroconverters. Seroconversion was significantly associated with malaria syndrome among nondiarrheic patients [adjusted odds ratio (aOR) = 4.0], night sweats (aOR = 1.4), and bilateral axillary (aOR = 1.6), inguinal (aOR = 2.2), and neck (aOR = 2.2) adenopathy relative to HIV-negative intervals. Median number of symptoms and findings was positively associated with set-point viral load (P < 0.001). CONCLUSION: Although most acute and early infections were asymptomatic, malaria syndrome was more common and more severe during seroconversion. When present, symptoms and physical examination findings were nonspecific and associated with higher set-point viremia. PMID- 22089382 TI - Suppression of murine melanoma growth by a vaccine of attenuated Salmonella carrying heat shock protein 70 and Herpes simplex virus-thymidine kinase genes. AB - Attenuated Salmonella can invade tumor cells and acts as a eukaryotic expression vector for gene propagation. We constructed a bi-gene, eukaryotic co-expression DNA vaccine of Mycobacterium tuberculosis heat shock protein 70 (mtHSP70) and Herpes simplex virus-thymidine kinase (HSV-tk) and used attenuated Salmonella as a vector to treat murine melanoma. In vitro, recombinant Salmonella can carry plasmid stably and can invade into the cytoplasm of B16 tumor cells expressing the protein of the mtHSP70/HSV-tk gene by Western blot assay. In vivo, after the recombinant Salmonella was injected into tumors, the HSV-tk precursor drug ganciclovir (GCV) was administered to start the HSV-tk killing of tumor cells. We found that the mtHSP70/HSV-tk recombinant bacteria can raise CD8+ T lymphocytes in peripheral blood by flow cytometry and in tumor tissues by immunofluorescence detection, increase IFN-gamma contents in tumor tissue by ELISA and significantly suppress tumor growth. PMID- 22089381 TI - Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission. AB - OBJECTIVE: The potential for changing HIV-1 virulence has significant implications for the AIDS epidemic, including changing HIV transmission rates, rapidity of disease progression, and timing of ART. Published data to date have provided conflicting results. DESIGN: We conducted a meta-analysis of changes in baseline CD4(+) T-cell counts and set point plasma viral RNA load over time in order to establish whether summary trends are consistent with changing HIV-1 virulence. METHODS: We searched PubMed for studies of trends in HIV-1 prognostic markers of disease progression and supplemented findings with publications referenced in epidemiological or virulence studies. We identified 12 studies of trends in baseline CD4(+) T-cell counts (21, 052 total individuals), and eight studies of trends in set point viral loads (10 ,785 total individuals), spanning the years 1984-2010. Using random-effects meta-analysis, we estimated summary effect sizes for trends in HIV-1 plasma viral loads and CD4(+) T-cell counts. RESULTS: Baseline CD4(+) T-cell counts showed a summary trend of decreasing cell counts [effect = -4.93 cells/MUl per year, 95% confidence interval (CI) -6.53 to -3.3]. Set point viral loads showed a summary trend of increasing plasma viral RNA loads (effect = 0.013 log(10) copies/ml per year, 95% CI -0.001 to 0.03). The trend rates decelerated in recent years for both prognostic markers. CONCLUSION: Our results are consistent with increased virulence of HIV-1 over the course of the epidemic. Extrapolating over the 30 years since the first description of AIDS, this represents a CD4(+) T cells loss of approximately 148 cells/MUl and a gain of 0.39 log(10) copies/ml of viral RNA measured during early infection. These effect sizes would predict increasing rates of disease progression, and need for ART as well as increasing transmission risk. PMID- 22089383 TI - Novel mechanically competent polysaccharide scaffolds for bone tissue engineering. AB - The success of the scaffold-based bone regeneration approach critically depends on the biomaterial's mechanical and biological properties. Cellulose and its derivatives are inherently associated with exceptional strength and biocompatibility due to their beta-glycosidic linkage and extensive hydrogen bonding. This polymer class has a long medical history as a dialysis membrane, wound care system and pharmaceutical excipient. Recently cellulose-based scaffolds have been developed and evaluated for a variety of tissue engineering applications. In general porous polysaccharide scaffolds in spite of many merits lack the necessary mechanical competence needed for load-bearing applications. The present study reports the fabrication and characterization of three dimensional (3D) porous sintered microsphere scaffolds based on cellulose derivatives using a solvent/non-solvent sintering approach for load-bearing applications. These 3D scaffolds exhibited a compressive modulus and strength in the mid-range of human trabecular bone and underwent degradation resulting in a weight loss of 10-15% after 24 weeks. A typical stress-strain curve for these scaffolds showed an initial elastic region and a less-stiff post-yield region similar to that of native bone. Human osteoblasts cultured on these scaffolds showed progressive growth with time and maintained expression of osteoblast phenotype markers. Further, the elevated expression of alkaline phosphatase and mineralization at early time points as compared to heat-sintered poly(lactic acid glycolic acid) control scaffolds with identical pore properties affirmed the advantages of polysaccharides and their potential for scaffold-based bone regeneration. PMID- 22089384 TI - Nitric oxide elicitation for secondary metabolite production in cultured plant cells. AB - Nitric oxide (NO) is an important signal molecule in stress responses. Accumulation of secondary metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. NO has been reported to play important roles in elicitor-induced secondary metabolite production in tissue and cell cultures of medicinal plants. Better understanding of NO role in the biosynthesis of such metabolites is very important for optimizing the commercial production of those pharmaceutically significant secondary metabolites. This paper summarizes progress made on several aspects of NO signal leading to the production of plant secondary metabolites, including various abiotic and biotic elicitors that induce NO production, elicitor-triggered NO generation cascades, the impact of NO on growth development and programmed cell death in medicinal plants, and NO-mediated regulation of the biosynthetic pathways of such metabolites. Cross-talks among NO signaling and reactive oxygen species, salicylic acid, and jasmonic acid are discussed. Some perspectives on the application of NO donors for induction of the secondary metabolite accumulation in plant cultures are also presented. PMID- 22089385 TI - Algal fucoidan: structural and size-dependent bioactivities and their perspectives. AB - Fucoidan is a complex-sulfated polysaccharide distributed in various marine organisms, and the brown algae are reported as the major producer. The fucoidan is important for their high bioactive properties, like antibacterial, anticoagulant, antiviral, anti-tumor, etc., and many more to be explored. There is a strong archival support for the bioactivity and promising properties of this molecule, which creates a hope for this molecule as future drug against thrombosis and some kind of cancers. Reports other than the above bioactive properties have also been a matter of interest for the design of signal or enzyme arrested new class of drugs. In the past three decades, the research on isolation, molecular characterization, and screening of biological applications has significantly increased. One major issue associated with this molecule is the higher size and seasonal variation in their chemical composition; to resolve the issue and maintain its bioactivity, a prioritized and literal hydrolysis process is required to be developed. Here, in this mini-review, we have tried to summarize the algal fucoidan research and the bioactivities influenced by their molecular size. PMID- 22089386 TI - Plasmid DNA fermentation strategies: influence on plasmid stability and cell physiology. AB - In order to provide sufficient pharmaceutical-grade plasmid DNA material, it is essential to gain a comprehensive knowledge of the bioprocesses involved; so, the development of protocols and techniques that allow a fast monitoring of process performance is a valuable tool for bioprocess design. Regarding plasmid DNA production, the metabolic stress of the host strain as well as plasmid stability have been identified as two of the key parameters that greatly influence plasmid DNA yields. The present work describes the impact of batch and fed-batch fermentations using different C/N ratios and different feeding profiles on cell physiology and plasmid stability, investigating the potential of these two monitoring techniques as valuable tools for bioprocess development and design. The results obtained in batch fermentations showed that plasmid copy number values suffered a pronounced increase at the end of almost all fermentation conditions tested. Regarding fed-batch fermentations, the strategies with exponential feeding profiles, in contrast with those with constant feeding, showed higher biomass and plasmid yields, the maximum values obtained for these two parameters being 95.64 OD(600) and 344.3 mg plasmid DNA (pDNA)/L, respectively, when using an exponential feed rate of 0.2 h(-1). Despite the results obtained, cell physiology and plasmid stability monitoring revealed that, although higher pDNA overall yields were obtained, this fermentation exhibited lower plasmid stability and percentage of viable cells. In conclusion, this study allowed clarifying the bioprocess performance based on cell physiology and plasmid stability assessment, allowing improvement of the overall process and not only plasmid DNA yield and cell growth. PMID- 22089387 TI - L-proline dehydrogenases in hyperthermophilic archaea: distribution, function, structure, and application. AB - Dye-linked L-proline dehydrogenase (ProDH) catalyzes the oxidation of L-proline to ?(1)-pyrroline-5-carboxylate (P5C) in the presence of artificial electron acceptors. The enzyme is known to be widely distributed in bacteria and eukarya, together with nicotinamide adenine dinucleotide (phosphate)-dependent P5C dehydrogenase, and to function in the metabolism of L-proline to L-glutamate. In addition, over the course of the last decade, three other types of ProDH with molecular compositions completely different from previously known ones have been identified in hyperthermophilic archaea. The first is a heterotetrameric alphabetagammadelta-type ProDH, which exhibits both ProDH and reduced nicotinamide adenine dinucleotide dehydrogenase activity and includes two electron transfer proteins. The second is a heterooctameric alpha(4)beta(4)-type ProDH, which uses flavin adenine dinucleotide, flavin mononucleotide, adenosine triphosphate, and Fe as cofactors and creates a new electron transfer pathway. The third is a recently identified homodimeric ProDH, which exhibits the greatest thermostability among these archaeal ProDHs. This minireview focuses on the functional and structural properties of these three types of archaeal ProDH and their distribution in archaea. In addition, we will describe the specific application of hyperthermostable ProDH for use in a biosensor and for DNA sensing. PMID- 22089388 TI - Decolorization of textile dyes by Alishewanella sp. KMK6. AB - Alishewanella sp. strain KMK6 was isolated from textile dye-contaminated soil. The strain was able to decolorize and degrade different azo dyes and displayed high dye degradation ability and tolerance. The bacterium could completely degrade 2.5 g l(-1) dye, Reactive Blue 59 within 6 h. The induction in the level of cytochrome P-450 and activities of azoreductase and NADH dichlorophenolindophenol reductase were observed in the cells after dye decolorization indicating the role of these enzymes. The intermediates of Reactive Blue 59 degradation were identified by high-performance liquid chromatography, gas chromatography and mass spectroscopy, and Fourier transform infrared spectroscopy. The ecotoxicity has been evaluated for dye and its metabolites by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (a yellow tetrazole) and comet assay, and it revealed that the dye degradation products were nontoxic. PMID- 22089389 TI - Agarose-gel-immobilized recombinant bacterial biosensors for simple and disposable on-site detection of phenolic compounds. AB - In this study, recombinant bacterial biosensors were immobilized in an agarose matrix and used for the simple and disposable field monitoring of phenolic compounds. In brief, Escherichia coli cells harboring the pLZCapR plasmid, which was previously designed to express the beta-galactosidase reporter gene in the presence of phenolic compounds, were immobilized in agarose gel with or without a substrate [chlorophenol red beta-galactopyranoside (CPRG)] and dispensed to the wells of a 96-well plate. Analytes were added to the wells, and color development was monitored either directly from wells containing intact cells co-immobilized with CPRG (SYS I), or using cells that were lysed prior to the addition of CPRG (SYS L). SYS L showed relatively higher intensities and faster color development than SYS I. However, both systems developed a red color (representing hydrolysis of CPRG) in the presence of 10 MUM to 10~100 mM phenol, with maximum responses seen at 1~5 and 50 mM phenol for SYS I and SYS L, respectively. Other phenolic compounds (2-chlorophenol, 2-methylphenol, 3-methylphenol, 4-chlorophenol, 2 nitrophenol, resorcinol, catechol, and 2,5-dimethylphenol) were also detected by the systems, with varied detection ranges and responses. The agarose-immobilized biosensors were stable for 28 days, retaining 39~69% of their activities when stored at 4 degrees C without nutrients or additives. The immobilized biosensors described herein do not require the on-site addition of a substrate (in the case of SYS I), the pretreatment of samples, or the use of unwieldy instruments for the on-site monitoring of phenolic compounds from environmental samples. PMID- 22089390 TI - Alteration in cell surface properties of Burkholderia spp. during surfactant aided biodegradation of petroleum hydrocarbons. AB - Chemical surfactants may impact microbial cell surface properties, i.e., cell surface hydrophobicity (CSH) and cell surface charge, and may thus affect the uptake of components from non-aqueous phase liquids (NAPLs). This work explored the impact of Triton X-100, Igepal CA 630, and Tween 80 (at twice the critical micelle concentration, CMC) on the cell surface characteristics of Burkholderia cultures, Burkholderia cepacia (ES1, aliphatic degrader) and Burkholderia multivorans (NG1, aromatic degrader), when grown on a six-component model NAPL. In the presence of Triton X-100, NAPL biodegradation was enhanced from 21% to 60% in B. cepacia and from 18% to 53% in B. multivorans. CSH based on water contact angle (50-52 degrees ) was in the same range for both strains while zeta potential at neutral pH was -38 and -31 mV for B. cepacia and B. multivorans, respectively. In the presence of Triton X-100, their CSH increased to greater than 75 degrees and the zeta potential decreased. This induced a change in the mode of uptake and initiated aliphatic hydrocarbon degradation by B. multivorans and increased the rate of aliphatic hydrocarbon degradation in B. cepacia. Igepal CA 630 and Tween 80 also altered the cell surface properties. For B. cepacia grown in the presence of Triton X-100 at two and five times its CMC, CSH increased significantly in the log growth phase. Growth in the presence of the chemical surfactants also affected the abundance of chemical functional groups on the cell surface. Cell surface changes had maximum impact on NAPL degradation in the presence of emulsifying surfactants, Triton X-100 and Igepal CA630. PMID- 22089391 TI - Heritability and longitudinal stability of impulsivity in adolescence. AB - Impulsivity is a multifaceted personality construct that plays an important role throughout the lifespan in psychopathological disorders involving self-regulated behaviors. Its genetic and environmental etiology, however, is not clearly understood during the important developmental period of adolescence. This study investigated the relative influence of genes and environment on self-reported impulsive traits in adolescent twins measured on two separate occasions (waves) between the ages of 11 and 16. An adolescent version of the Barratt Impulsiveness Scale (BIS) developed for this study was factored into subscales reflecting inattention, motor impulsivity, and non-planning. Genetic analyses of these BIS subscales showed moderate heritability, ranging from 33-56% at the early wave (age 11-13 years) and 19-44% at the later wave (age 14-16 years). Moreover, genetic influences explained half or more of the variance of a single latent factor common to these subscales within each wave. Genetic effects specific to each subscale also emerged as significant, with the exception of motor impulsivity. Shared twin environment was not significant for either the latent or specific impulsivity factors at either wave. Phenotypic correlations between waves ranged from r = 0.25 to 0.42 for subscales. The stability correlation between the two latent impulsivity factors was r = 0.43, of which 76% was attributable to shared genetic effects, suggesting strong genetic continuity from mid to late adolescence. These results contribute to our understanding of the nature of impulsivity by demonstrating both multidimensionality and genetic specificity to different facets of this complex construct, as well as highlighting the importance of stable genetic influences across adolescence. PMID- 22089392 TI - High serum matrix metalloproteinase 3 is characteristic of patients with paraneoplastic remitting seronegative symmetrical synovitis with pitting edema syndrome. AB - Recently, it was reported that remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome could be complicated with solid tumors. In a retrospective, multicenter study between October, 2003 and September, 2010, we investigated the characteristics of patients with paraneoplastic RS3PE syndrome who fulfilled following criteria: (1) bilateral pitting edema of hands or feet or both, (2) sudden onset of polyarthritis, and (3) age >50 years, (4) seronegativity for rheumatoid factor (RF). A total of 33 cases fulfilled the above criteria. Eight patients (seven men and one woman) developed cancer within 2 years of RS3PE syndrome onset. There was no significant difference between the neoplastic and nonneoplastic groups in the proportions of patients with fever, symmetrical polyarthritis, pitting edema, and good response to corticosteroids. Serum matrix metalloproteinase 3 (MMP-3) level (median 437.3 ng/ml) in the paraneoplastic RS3PE patients was significantly higher than that in patients without neoplasia (median 114.7 ng/ml) (p < 0.05). We found that high serum MMP-3 is characteristic of patients with paraneoplastic RS3PE syndrome. PMID- 22089393 TI - The biomechanical effect of pedicle screws' insertion angle and position on the superior adjacent segment in 1 segment lumbar fusion. AB - STUDY DESIGN: A finite element analysis. OBJECTIVE: To investigate the association between the position of an inserted pedicle screw and the corresponding facet contact force or intradiscal pressure. SUMMARY OF BACKGROUND DATA: Although superior facet joint violation by pedicle screws is not an uncommon occurrence in instrumented lumbar fusion surgery, its actual biomechanical significance is not well understood. Furthermore, the association between the position of the pedicle screw and the stress on the corresponding disc/facet joint has yet to be investigated. METHODS: According to the positions of pedicle screws in L4 of the L4-L5 lumbar fusion, 4 L4-L5 fusion models were simulated. These models included the violation of both L3-L4 superior facet joints by pedicle screws (facet joint violation [FV] model), the nonencroachment of both L3-L4 superior facet joints by pedicle screws (facet joint preservation [FP] model), and the removal state of pedicle screws in the FV model (removal of violated pedicle screws [rFV] model). The facet joint contact [FC] model represented the scenario in which the pedicle screws did not encroach upon either facet joint but were inserted close to the L3-L4 facet joint surface. Moreover, the uninstrumented fusion [UF] model represented the uninstrumented L4-L5 fusion. In each scenario, the intradiscal pressures and facet contact forces at the L2-L3 and L3-L4 segments were analyzed under extension and torsion moments. RESULTS: The FV model yielded the greatest increases in facet contact force and intradiscal pressure at the L3-L4 segment under extension and torsion moments. Following the FV model, the increases in intradiscal pressure and facet contact force were the second highest in the FC model followed by the FP model. Furthermore, the rFV model represented prominent reductions of previously increased facet contact force and intradiscal pressure at the L3-L4 segment. CONCLUSION: In models of 1-segment lumbar fusion surgery, the positions of pedicle screws were closely linked with corresponding disc stresses and facet contact forces. However, even in cases of facet violation by pedicle screws, removal of the pedicle screw after fusion completion can reduce facet contract forces and disc stresses under both extension and torsional moments. PMID- 22089394 TI - WITHDRAWN:Comparison of Tracheal Intubation Using The Different Devices in a Cadaver Model with Cervical Instability. PMID- 22089395 TI - Atlas injury mechanisms during head-first impact. AB - STUDY DESIGN: An in vitro biomechanical study. OBJECTIVE: To investigate atlas injury mechanisms due to horizontally aligned head-first impacts of a cadaveric neck model and to document atlas fracture patterns and associated injuries. SUMMARY OF BACKGROUND DATA: Experimental atlas injuries have been created by applying compression or radial forces to isolated C1 vertebrae, dropping weight or applying sagittal moments to the upper cervical spine segments, or vertical drop testing of head-neck specimens or whole cadavers. Atlas injuries that commonly occur due to horizontally aligned head-first impacts have not been previously investigated. METHODS: Horizontally aligned head-first impacts into a padded barrier were simulated at 4.1 m/s, using a human cadaver neck model mounted horizontally to a torso-equivalent mass on a sled and carrying a surrogate head. Atlantal radial force was computed using head and neck load cell data. Postimpact dissection documented atlas and associated injuries. Average atlantal radial force peaks and their occurrence times were statistically compared (P < 0.05) among the first local and global peaks using paired t tests. RESULTS: The first average local peak in radial atlantal force was significantly smaller (1240 vs. 2747 N) and occurred significantly earlier (24 ms vs. 46 ms) than the global force peak. Atlas injuries consisted of either 3- or 4-part burst fractures or incomplete lateral mass fracture unilaterally. Associated injuries included bony avulsion of the transverse ligament unilaterally and fractures of the occipital condyles, superior facets of the axis, or odontoid. CONCLUSION: The results indicated that the varied atlas fracture patterns were due primarily to radial forces causing outward lateral expansion of its lateral masses. Anterior and posterior arch fracture locations are dependent, in part, upon the cross sectional arch dimensions. Transverse ligament rupture or bony avulsion is likely associated with real-life atlantal burst fractures. PMID- 22089396 TI - Delayed formation of a devastating granulomatous process after metal-on-metal lumbar disc arthroplasty. AB - STUDY DESIGN: A case report. OBJECTIVE: We report the case of a female patient with a delayed and devastating complication after lumbar total disc arthroplasty (TDA). SUMMARY OF BACKGROUND DATA: The formation of granulomatous tissue surrounding arthroplasty devices has been described after hip replacements, but has been reported only in a few cases after spinal surgery. METHODS: Retrospective case study of a female patient with a delayed complication after lumbar TDA with a metal-on-metal device for degenerative disc disease at level L4 L5 and with follow-up examination 8 months after surgery. RESULTS: About 11 months after lumbar arthroplasty surgery, the patient developed back pain and progressive weakness of both legs. A computed tomographic scan revealed soft tissue surrounding the TDA device and infiltrating the spinal canal. The revision surgery (posterior fixation and decompression) did not improve the clinical situation. The progressive growth of soft tissue led to a high-grade paraparesis and occlusion of the left ureter as well as of both common iliac veins and the infrarenal part of the vena cava inferior. The TDA device was removed. Another posterior surgery with extensive instrumentation was necessary to treat the destruction of vertebral bodies L4 and L5 2 months after the last surgery. The histopathological analysis revealed a granulomatous necrotizing inflammation. After the last revision surgery, the patient's back pain decreased. At her last follow-up, no further growth of the soft tissue mass could be found. CONCLUSION: Metal-on-Metal TDA devices can induce a tumor-like growth with devastating consequences. The reduction of device motion by posterior stabilizing surgery does not seem to stop the growth of the granulomatous mass. The device has to be removed. PMID- 22089397 TI - The association of patient characteristics and spinal curve parameters with Lenke classification types. AB - STUDY DESIGN: Retrospective review. OBJECTIVE: To determine the association of patient characteristics and spinal curve parameters with Lenke curve types. SUMMARY OF BACKGROUND DATA: The Lenke curve classification may be used for surgical planning and clinical research. METHODS: We retrospectively reviewed the records of 1912 patients with adolescent idiopathic scoliosis who underwent initial surgery at 21 years of age or younger; collected data on patient's age, patient's sex, primary curve magnitude (<50 degrees , 50 degrees -75 degrees , and .75 degrees ), and Scoliosis Research Society (SRS) outcomes questionnaire (SRS-22) score; and compared that data by Lenke curve type. Analysis of variance and chi tests were used as appropriate (significance level, P <= 0.005). RESULTS.: Lenke types vary by sex: male patients had more major thoracic (types 1 4) than major thoracolumbar/lumbar (types 5 and 6) curves, fewer lumbar C modifiers (32% vs. 44%), and less apical lumbar translation (1.1 vs. 1.7 cm). Lenke types vary by frequency: the most common type was 1 (50%); the least common, 4 (4%). Lenke types vary by magnitude: type 4 had the greatest percentage of large curves (52% of curves .75 degrees ), most smaller curves were types 1 and 5, and type 4 had the largest mean magnitude (78 degrees +/- 17 degrees ). Lenke types vary by patient age: type 5 curves occurred in the oldest patients (average age at surgery: 15.4 +/- 2.2 vs. 14.3 +/- 14.6 years for all others) despite having the lowest mean magnitude (P = 0.001); curve size was negatively correlated with age at surgery (r = -0.16, P = 0.001). Lenke types vary by patient self-image: patients with type 4 curves had lower preoperative SRS outcome scores for self-image than did patients with type 1 curves (P = 0.005). CONCLUSION: Lenke types vary by sex, frequency magnitude, patient age, and patient self-image, which should be considered in designing studies. PMID- 22089398 TI - Is surgical case order associated with increased infection rate after spine surgery? AB - STUDY DESIGN: Retrospective database review. OBJECTIVE: To determine whether surgical site infections are associated with case order in spinal surgery. SUMMARY OF BACKGROUND DATA: Postoperative wound infection is the most common complication after spinal surgery, with incidence varying from 0.5% to 20%. The addition of instrumentation, use of preoperative prophylactic antibiotics, length of procedure, and intraoperative blood loss have all been found to influence infection rate. No previous study has attempted to correlate case order with infection risk after surgery. METHODS: A total of 6666 spine surgery cases occurring between January 2005 and December 2009 were studied. Subjects were classified into 2 categories: fusion and decompression. Case order was determined, with each procedure labeled 1 to 5 depending on the number of previous cases in the room. Variables such as the American Society of Anesthesiologists score, number of operative levels, wound class, age, sex, and length of surgery were also tracked. A step-down binary regression was used to analyze each variable as a potential risk factor for infection. RESULTS: Decompression cases had a 2.4% incidence of infection. Longer surgical time and higher case order were found to be significant risk factors for lumbar decompressions. Fusion cases had a 3.5% incidence of infection. Posterior approach and revision cases were significant risk factors for infection in cervical cases. For lumbar fusion cases, longer surgical time, higher American Society of Anesthesiologists score, and older age were all significant risk factors for infection. CONCLUSION: Decompressive procedures performed later in the day carry a higher risk for postoperative infection. No similar trend was shown for fusion procedures. Our results identify potential modifiable risk factors contributing to infection rates in spinal procedures. Specific risk factors, although not defined in this study, might be related to contamination of the operating room, cross-contamination between health care providers during the course of the day, use of flash sterilization, and mid-day shift changes. PMID- 22089400 TI - Primary spinal natural killer/T-cell lymphoma successfully treated with concurrent chemoradiotherapy and autologous stem cell transplantation. AB - STUDY DESIGN: This case report shows primary natural killer (NK)/T-cell lymphoma originating in the spine as the first case of successful treatment with autologous stem cell transplantation, along with case presentation and literature review. OBJECTIVE: For the proper treatment of this spinal tumor, the pathologic confirmation includes immunophenotypic profiling, the understanding of tumor characteristics, and the consideration of spinal stability are necessary. SUMMARY OF BACKGROUND DATA: NK/T-cell lymphomas are rare, aggressive neoplastic disorders with a distinctive clinical pathologic profile and an unfavorable clinical prognosis. The extranodal nasal-type NK/T-cell lymphomas, which are characterized by an extranodal presentation and an aggressive clinical course, are prevalent in Asia and Central and South America. METHODS: A 49-year-old woman presented with thoracic back pain that developed 3 months before she was admitted to Chung-Ang University. The radiological image showed a 6 * 4 * 5-cm mass lesion within the T6-T7 vertebral body. The histopathology was consistent with the finding of NK/T cell lymphoma. Treatment with chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) in combination with radiotherapy (total dose, 30 Gy) was done, and salvage therapy with autologous stem cell transplantation was performed. RESULTS: Two-year follow-up magnetic resonance image showed shrinking remnant mass without spinal deformation and/or instability. Rebiopsy for remnant mass, nasal area study, and positron emission tomographic scan were performed to determine the tumor recurrence. There was no evidence of recurrence at the 2-year follow-up evaluations. CONCLUSION: Some primary NK/T-cell lymphomas that originate at sites other than the nasal cavity/nasopharynx do not present with typical clinical features and symptoms. A primary NK/T-cell lymphoma of the spine should be considered in the differential diagnosis of primary bone tumors. We report the first case of successful treatment with chemoradiotherapy and autologous stem cell transplantation in a patient with a primary spinal NK/T-cell lymphoma. PMID- 22089401 TI - Development of the Simplified Chinese Version of the Spinal Appearance Questionnaire: cross-cultural adaptation and psychometric properties evaluation. AB - STUDY DESIGN: Cross-cultural adaptation and psychometric testing of the Spinal Appearance Questionnaire (SAQ). OBJECTIVE: To evaluate the reliability and validity of simplified Chinese version of the SAQ (SC-SAQ). SUMMARY OF BACKGROUND DATA: The SAQ is widely used to assess the perception of spinal appearance in patients with adolescent idiopathic scoliosis (AIS). However, there is no culturally adapted, reliable, and validated SAQ for mainland China. METHOD: The cross-cultural adaptation of the original SAQ was performed following international guidelines. The SC-SAQ was administered concurrently with the simplified Chinese version of the Scoliosis Research Society-22 (SC-SRS-22) questionnaire to 223 patients with AIS. A total of 92 patients were randomly selected to complete the questionnaires again 4 to 7 days after the first completion. Psychometric testing included reliability by internal consistency and test-test reliability, convergent validity by comparing the SC-SAQ with the SC SRS-22 appearance domain, and discriminant validity by analyzing the relationship between SC-SAQ scores and patients' characteristics. RESULT: Internal consistency for the SC-SAQ was satisfactory, with intradomain correlations ranging from r = 0.526 to r = 0.808 (P, 0.0001). The test-retest reliability for the SC-SAQ was excellent with intraclass correlation coefficient of 0.933 (95% confidence interval = 0.903-0.956) and good Bland-Altman agreement. (No systematic bias was found in the Bland-Altman plot.) Convergent validity test demonstrated a moderate correlation between the overall SC-SAQ and SC-SRS-22 appearance domain, with rho = -0.401 (P, 0.0001). Correlation between the overall SC-SAQ and the major curve magnitude was significant, with r = 0.827 (P, 0.0001). Discriminant validity was confirmed by significant differences of overall SC-SAQ and individual domain scores among the 6 subgroups categorized by the major curve magnitude (P, 0.0001) and among patients requiring exercise, bracing, or surgery (P, 0.0001). CONCLUSION: The SC-SAQ showed satisfactory reliability and validity in the evaluation of spinal deformity appearance for patients with AIS in mainland China. PMID- 22089402 TI - Unknown case: part 2. Spontaneous regression of herniated disc. PMID- 22089403 TI - Silanetriols in the gas phase: single molecules vs. hydrogen-bonded dimers. AB - The first gas phase structure of a silanetriol, tert-butylsilane-triol [(t)BuSi(OH)(3)], determined by gas electron diffraction (GED), is reported. Quantum chemical calculations have been performed to elucidate potential intermolecular interactions between silanetriol molecules in the gas phase. The results are set into contrast to solid state structures of (t)BuSi(OH)(3) and related compounds. PMID- 22089404 TI - Reimagining nursing quality in the accountable care landscape. PMID- 22089405 TI - Effect of early nutritional support on intensive care unit length of stay and neurological status at discharge in children with severe traumatic brain injury. AB - Pediatric severe traumatic brain injury treatment guidelines for nutrition indicate that "there are insufficient data to support a treatment guideline for this topic" (P. D. Adelson et al., 2003). Based on adult studies, the guideline provided an option for practitioners to start nutritional support within 72 hours of admission and full replacement by day 7. This retrospective, descriptive correlation study examined the timing of nutritional supplement initiation and the timing of achieving full caloric intake in relation to length of stay (LOS) in the intensive care unit (ICU) and patient disposition status at discharge from hospital in children 8-18 years old. Median time to initiation of nutrition was 1.5 days (0.02-11.9 days), and full caloric goals were achieved in 3.4 days (0.5 19.6 days). Median ICU LOS was 2.1 days (0.01-97.9 days). Overall, 48% of patients were discharged home; 28% experienced mild, moderate, or severe disability; and 24% either died or survived in a vegetative state. Early initiation and achieving full caloric intake were both positively correlated with shorter LOS in the ICU (p < .01, Spearman's rho correlational matrix) and better disposition status at discharge from the hospital (p < .05, Kruskal-Wallis test). PMID- 22089406 TI - The effects of exercise-based rehabilitation on balance and gait for stroke patients: a systematic review. AB - This review evaluated the effects of balance and/or gait exercise interventions for stroke survivors and summarized the available evidence on these exercise interventions. A search for studies published between January 2001 and January 2010 was performed using the keywords stroke, walking or balance, and physical activity or exercise. Seventeen randomized clinical trials were identified. The findings suggest that initiating early rehabilitation during acute to subacute stroke recovery can improve balance and walking capacity. The findings also demonstrate that at least 1 hour, three to five times per week, of balance training and 30 minutes, three to five times per week, of gait-oriented exercise are effective to improve balance and walking. This review confirms that balance and walking capacity are improved with specific exercise modalities. A combination of balance, gait, and aerobic exercises would be ideal. PMID- 22089407 TI - "Tap and twist": preventing deep vein thrombosis in neuroscience patients through foot and ankle range-of-motion exercises. AB - Neurosurgical patients tend to have the highest rate of deep vein thrombosis (DVT) rate among other postsurgical patients. The methods and timing of DVT prevention and treatment continue to be debated among neurointensivists. The greatest opportunity to intervene is early during the stay in the intensive care unit. There are many factors, however, that can make this the most neglected time for aggressive prevention measures. For large university teaching hospitals, the target of the University Health System Consortium is to achieve an average DVT rate at or below half that of previous reported rates. The current recommendations are effective only if there is compliance with these measures during the majority of the patients' hospitalization. Our hypothesis states that without changing any of the current measures to prevent DVT, a structured program of foot and ankle range-of-motion (ROM) exercises will decrease the incidence of DVT in the neuroscience intensive care patient population. This quasi experimental study was a quality improvement project examining 315 individuals over the age of 18 years, who were admitted to the neurospine intensive care unit and who received a new program of foot exercises as a method of DVT prevention. Data for the outcome measures were derived from bedside measurement of lower extremity doppler, the percentage of time the exercises were performed, patient history, and standard DVT prevention measures. Overall, there was no difference in DVT rates for those receiving the foot ROM intervention during the study period in 2008-2009 compared with the usual nursing practice for the previous year. However, during the study period, those who developed DVT had a significantly lower compliance rate with the ROM exercises (38.7%) than did those who did not develop DVT (58.4%; p < .001). Therefore, foot and ankle ROM exercises may have a promising role in reducing the incidence of DVT in neuroscience intensive care patients when there is diligent performance of the exercises. PMID- 22089409 TI - Content validity and acceptability of the daily enhancement of meaningful activity program: intervention for mild cognitive impairment patient-spouse dyads. AB - Persons with mild cognitive impairment (PwMCI) are at greater risk for developing Alzheimer disease and experience various difficulties that decrease their quality of life. Very few interventions focus on helping PwMCI improve or maintain functional performance and enhance quality of life through meaningful activity engagement. The purpose of the study was to explore PwMCI and their spouses' perspectives on the content validity, usefulness, and acceptability of the Daily Enhancement of Meaningful Activity (DEMA) program, which included 6 biweekly face to-face sessions between session assignments and a self-management tool kit of written educational handouts. Nine PwMCI-care partner dyads participated in 3 focus groups (PwMCI alone, spouses alone, and couples) to capture their perspectives on DEMA. The transcribed focus group data were analyzed through content analysis. The three groups provided support for content validity and acceptability of the program, and they suggested additional content areas important to couples experiencing MCI. They also attested to the usefulness of the tool kit and gave suggestions for its further improvement. The findings provide evidence of the content validity and acceptability of the DEMA program. A pilot study to assess feasibility and preliminary efficacy of the DEMA on health related outcomes is the recommended next research step for this program. PMID- 22089410 TI - A qualitative assessment of practices associated with shorter door-to-needle time for thrombolytic therapy in acute ischemic stroke. AB - Early treatment with intravenous (IV) recombinant tissue plasminogen activator/alteplase (tPA) is associated with improved outcomes for patients with an acute ischemic stroke. Thus, rapid triage and treatment of stroke patients are essential, with a goal of door-to-needle time of no more than 60 minutes. We sought to identify best practices associated with faster treatment among hospitals participating in Get With the Guidelines--Stroke. Qualitative telephone interviews were conducted to elicit strategies being used by these centers to assess, treat, and monitor stroke patients treated with IV tPA. We sequentially carried out these interviews until we no longer identified novel factors. Interviews were conducted with 13 personnel at 7 top-performing U.S. hospitals. With the use of a hermeneutic-phenomenological framework, 5 distinct domains associated with rapid IV tPA delivery were identified. These included (a) communication and teamwork, (b) process, (c) organizational culture, (d) performance monitoring and feedback, and (e) overcoming barriers. PMID- 22089411 TI - Support for traumatic brain injury patients' family members in neurosurgical nursing: a systematic review. AB - This systematic literature review describes how adult traumatic brain injury (TBI) patients' family members received support. The research question was "What in healthcare constitutes support for a TBI patient's family members?" The data for this review were based on 22 empirical studies published in scientific journals in 2004-2010, which were found in the Cinahl, PsychINFO, and ISI Web of Knowledge databases. The review includes the study design, sample, method, and main results. The data were analyzed using content analysis. Social support for brain injury patients' family members was divided into 3 main categories: informational, emotional, and practical support. The subcategories of informational support were information about the patient's symptoms, information about care, quality of information, and information about the prognosis. The subcategories of emotional support were taking emotions into account, caring, listening, and respecting. The subcategories of practical support were support in decision making, promoting the welfare of the family, encouraging family members to participate in care, cooperation with the family members, and counseling services. The results are available for nurses in practical work. The review offers nurses a structure for supporting TBI patients' families, and according to this review, supporting TBI patients' families appears to have many dimensions. The results suggest that nurses should be informed that it is important for family members to know the facts about TBI to understand the condition and to receive practical advice on how to help their significant other with TBI with daily activities. In addition, the results provide a basis for further research and development of interventions that support brain injury patients and their family members. PMID- 22089412 TI - Use of simulation in stroke unit education. PMID- 22089413 TI - Clinical practice guideline series update. PMID- 22089414 TI - HPV vaccine update: new indications and controversies. AB - Human papillomavirus (HPV) has a predilection for infecting epidermal and mucosal surfaces such as those of the anogenital region. HPV causes substantial pre malignant, malignant, and benign disease in both women and men, ranging from cervical, vulvar, penile, and anal cancers to condyloma acuminata (genital warts). Although HPV vaccination is becoming more common, infection rates remain high in both genders. Perception of HPV vaccine has largely centered on its ability to prevent cervical cancer in women, though indication for its use in men is expanding. The benefits to men include prevention of genital warts and, more recently, regulatory approval was expanded in the US for prevention of anal cancer. Herein, we review HPV vaccine with a focus on its new indication in men and existing controversies. PMID- 22089415 TI - Botulinum toxin type A: new information about an old medicine. AB - Now that several formulations of botulinum toxin type-A (BoNT-A) are on the market in North America and throughout the world, it is of great practical importance for those who administer these medications to be familiar with the differences between the formulations. These differences pertain to the stability of the medications, in particular during the period of time between reconstitution and administration, which may affect the degree of diffusion through various tissues after injection. A variety of relatively new uses of BoNT A for dermatological conditions will be discussed. PMID- 22089416 TI - QM/MM simulation of liquid water with an adaptive quantum region. AB - The simulation of complex chemical systems often requires a multi-level description, in which a region of special interest is treated using a computationally expensive quantum mechanical (QM) model while its environment is described by a faster, simpler molecular mechanical (MM) model. Furthermore, studying dynamic effects in solvated systems or bio-molecules requires a variable definition of the two regions, so that atoms or molecules can be dynamically re assigned between the QM and MM descriptions during the course of the simulation. Such reassignments pose a problem for traditional QM/MM schemes by exacerbating the errors that stem from switching the model at the boundary. Here we show that stable, long adaptive simulations can be carried out using density functional theory with the BLYP exchange-correlation functional for the QM model and a flexible TIP3P force field for the MM model without requiring adjustments of either. Using a primary benchmark system of pure water, we investigate the convergence of the liquid structure with the size of the QM region, and demonstrate that by using a sufficiently large QM region (with radius 6 A) it is possible to obtain radial and angular distributions that, in the QM region, match the results of fully quantum mechanical calculations with periodic boundary conditions, and, after a smooth transition, also agree with fully MM calculations in the MM region. The key ingredient is the accurate evaluation of forces in the QM subsystem which we achieve by including an extended buffer region in the QM calculations. We also show that our buffered-force QM/MM scheme is transferable by simulating the solvated Cl(-) ion. PMID- 22089417 TI - Cancer stem cells. VEGF promotes stemness. PMID- 22089418 TI - Lymphoma. Suppressive EPH-ect. PMID- 22089419 TI - Genetics. BRCA inequality. PMID- 22089422 TI - Clinical observation of a 16-year-old female exposed to radiation in utero: follow-up after the Shanxi Xinzhou radiation accident. AB - A follow-up study of the late effects of intrauterine exposure to irradiation has been made on a 16-year-old girl whose mother was exposed to external (60)Co irradiation during the Xinzhou radiation accident 16 years previously. The outcomes of the general medical examinations, conventional chromosome aberration analyses and fluorescence in situ hybridisation (FISH) are presented and the China-revised Wechsler Intelligence Scale for Children (C_WISC) was used to identify her IQ level, which was well below normal for her age. The biological dose of the radiation to which she was exposed when she was in her mother's uterus was inferred to be 1.85 Gy. Although there is no evidence of any other developmental changes or tumour induction at this stage in her life, the child's total intelligence level does appear to have been affected. PMID- 22089420 TI - Choline metabolism in malignant transformation. AB - Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, the modulation of enzymes that control anabolic and catabolic pathways causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These increased levels are associated with proliferation, and recent studies emphasize the complex reciprocal interactions between oncogenic signalling and choline metabolism. Because choline-containing compounds are detected by non-invasive magnetic resonance spectroscopy (MRS), increased levels of these compounds provide a non-invasive biomarker of transformation, staging and response to therapy. Furthermore, enzymes of choline metabolism, such as choline kinase, present novel targets for image-guided cancer therapy. PMID- 22089421 TI - Gastrointestinal stromal tumours: origin and molecular oncology. AB - Gastrointestinal stromal tumours (GISTs) are a paradigm for the development of personalized treatment for cancer patients. The nearly simultaneous discovery of a biomarker that is reflective of their origin and the presence of gain-of function kinase mutations in these tumours set the stage for more accurate diagnosis and the development of kinase inhibitor therapy. Subsequent studies of genotype and phenotype have led to a molecular classification of GIST and to treatment optimization on the basis of molecular subtype. The study of drug resistant tumours has advanced our understanding of kinase biology, enabling the development of novel kinase inhibitors. Further improvements in GIST treatment may require targeting GIST stem cell populations and/or additional genomic events. PMID- 22089423 TI - Validity of a short questionnaire to assess physical activity in 10 European countries. AB - To accurately examine associations of physical activity (PA) with disease outcomes, a valid method of assessing free-living activity is required. We examined the validity of a brief PA questionnaire (PAQ) used in the European Prospective Investigation into Cancer and Nutrition (EPIC). PA energy expenditure (PAEE) and time spent in moderate and vigorous physical activity (MVPA) was measured in 1,941 healthy individuals from 10 European countries using individually-calibrated combined heart-rate and movement sensing. Participants also completed the short EPIC-PAQ, which refers to past year's activity. Pearson (r) and Spearman (sigma) correlation coefficients were calculated for each country, and random effects meta-analysis was used to calculate the combined correlation across countries to estimate the validity of two previously- and one newly-derived ordered, categorical PA indices ("Cambridge index", "total PA index", and "recreational index") that categorized individuals as inactive, moderately inactive, moderately active, or active. The strongest associations with PAEE and MVPA were observed for the Cambridge index (r = 0.33 and r = 0.25, respectively). No significant heterogeneity by country was observed for this index (I(2) = 36.3%, P = 0.12; I(2) = 0.0%, P = 0.85), whereas heterogeneity was suggested for other indices (I(2) > 48%, P < 0.05, I(2) > 47%, P < 0.05). PAEE increased linearly across self-reported PA categories (P for trend <0.001), with an average difference of approximately 460 kJ/d for men and 365 kJ/d for women, between categories of the Cambridge index. The EPIC-PAQ is suitable for categorizing European men and women into four distinct categories of overall physical activity. The difference in PAEE between categories may be useful when estimating effect sizes from observational research. PMID- 22089424 TI - The influence of non-response in a population-based cohort study on type 2 diabetes evaluated by the Swedish Prescribed Drug Register. AB - Bias due to non-response in observational studies may lead to false risk estimates. We evaluated potential selective non-response in Stockholm Diabetes Prevention Program (SDPP) using a population-based drug register. A cohort of 12,952 men and 19,416 women, aged 35-56 years, was screened for diabetes and family history of diabetes (FHD). Response rate: 79% in men and 85% in women. Of the 4,209 men and 6,916 women that were invited, 70 and 68% participated in a baseline health examination including oral glucose tolerance test. A follow-up was performed in 79% of male and 70% of female baseline participants. We used data from the prescription register to estimate absolute risks and ORs for drug treated diabetes in the non-response/non-participation groups. At both screening and baseline steps absolute risks of drug-treated diabetes were equal in non participants and participants. Adjusted ORs were 0.9-1.0. At follow-up, absolute risks were higher among non-participants than participants, men 6.2/4.4% and women 2.6/1.6%, adjusted ORs 1.4 (0.9-2.3) and 1.5 (0.9-2.4), suggesting selective non-participation. Further analyses of FHD, smoking, physical activity, socioeconomic position and psychological distress demonstrated no previous false risk estimates for type 2 diabetes. However, for body mass index, there were indications of overestimation in women. We conclude that bias from non-response was not present at screening or baseline steps, suggesting that diabetes prevalence and risks may be estimated from a population-based cohort study with high attendance rate such as the SDPP. However, follow-up data should be treated with some caution, since the sample may have become biased. PMID- 22089426 TI - Changes in NMDA-receptor function in the first week following laser-induced lesions in rat visual cortex. AB - Focal brain injuries are accompanied by processes of functional reorganization that partially compensate the functional loss. In a previous study, extracellular recordings at the border of a laser-induced lesion in the visual cortex of rats showed an enhanced synaptic plasticity, which was mediated by the activity of NR2B-contaning NMDA-receptors (NMDARs) shedding light on the potential cellular mechanisms underlying this reorganization. Given the potentially important contribution of NMDARs in processes of functional reorganization, in the present study, we used the same lesion model to further investigate lesion-induced changes in function and localization of NMDARs in the vicinity of the lesion. The most important finding was a lesion-mediated functional reexpression of nonpostsynaptic, but according to our data, presynaptic or peri-/extrasynaptic NMDARs (preNMDARs), which were undetectable in age-matched (>P21) sham-operated controls. Notably, preNMDARs were able to boost both spontaneous and evoked synaptic glutamatergic transmission. At the postsynaptic site, we also disclosed an increase in the decay time constant of NMDARs mediated currents, which was accompanied by a decreased NR2A/NR2B ratio, as revealed by Western blot analysis. All together these findings provide new insights into the role of NMDARs activity during processes of functional reorganization following a focal lesion in the cerebral cortex. PMID- 22089425 TI - Cell type-specific three-dimensional structure of thalamocortical circuits in a column of rat vibrissal cortex. AB - Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory evoked spiking. Here, we reconstruct the 3D circuits formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify 9 cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamocortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type-specific lemniscal synaptic wiring diagram and elucidates structure-function relationships of this physiologically relevant pathway at single-cell resolution. PMID- 22089427 TI - C-H and C-O oxidative addition in reactions of aryl carboxylates with a PNP pincer-ligated Rh(I) fragment. AB - Reactions of a series of phenyl esters with a (PNP)Rh fragment have been studied. PhO(2)CPh only underwent C-H oxidative addition (OA). PhO(2)CCF(3) chiefly underwent acyl-oxygen OA. PhO(2)CBu(t) and PhO(2)CNEt(2) initially underwent OA of an ortho-C-H bond of the phenyl group but continued thermolysis led to the phenyl-oxygen OA products. PMID- 22089428 TI - Feasibility of stopping paclitaxel premedication after two doses in patients not experiencing a previous infusion hypersensitivity reaction. AB - PURPOSE: Paclitaxel-based chemotherapy continues to be an integral component in the treatment of many solid tumors. Prolonged use of paclitaxel may result in repeated doses of premedications and potential unwanted side effects. Infusion hypersensitivity reactions occurring beyond the second dose are infrequent and not well characterized. We hypothesized that patients whose paclitaxel premedications were discontinued after two doses were unlikely to experience infusion hypersensitivity reactions with subsequent paclitaxel doses. METHODS: Patients receiving paclitaxel-based chemotherapy who did not experience an infusion hypersensitivity reaction with their first or second dose had their paclitaxel premedications discontinued. The primary endpoint was to estimate the incidence of rescue medication for the treatment of paclitaxel infusion hypersensitivity during doses 3 to 6 for patients whose paclitaxel premedications had been discontinued. RESULTS: After receiving the first two doses of paclitaxel based chemotherapy without experiencing an infusion hypersensitivity reaction (any grade), 55 breast cancer patients had their premedications discontinued for all remaining paclitaxel doses. None of these patients required rescue medication to treat an infusion hypersensitivity reaction with subsequent doses. CONCLUSIONS: In patients who have not experienced an infusion hypersensitivity reaction with the first two doses of paclitaxel, discontinuation of paclitaxel premedications may be considered an option without an increased risk of infusion hypersensitivity requiring rescue medication. PMID- 22089429 TI - Aprepitant, dexamethasone, and palonosetron in the prevention of doxorubicin/cyclophosphamide-induced nausea and vomiting. AB - PURPOSE: This study evaluated the efficacy and tolerability of aprepitant, dexamethasone, and palonosetron in the prevention of nausea and vomiting in breast cancer patients receiving their initial cycle of doxorubicin and cyclophosphamide (AC). METHODS: Patients with breast cancer, >= age 18, with a performance status of <= 2, receiving doxorubicin (>= 60 mg/m(2)) and cyclophosphamide (>= 500 mg/m(2)) for the first time were eligible. Prior to chemotherapy patients received aprepitant 125 mg orally (PO), dexamethasone 8-10 mg PO/intravenously (IV), and palonosetron 0.25 mg IV. On days 2-3, dexamethasone 4 mg PO and aprepitant 80 mg PO were given. Outcomes were recorded in patient diaries for the 120-h study period following chemotherapy. Primary endpoint was the proportion of patients achieving complete response (no emesis or rescue) for the 120-h study period. RESULTS: Thirty-six patients were enrolled and all are evaluable. The median age was 53 (33-75) and 36 are females. Eighteen patients (50%) achieved a complete response during the 120-h study period. Acute (<= 24 h) and delayed (24-120 h) complete response rates were 81% (27/36) and 61% (22/36), respectively. No emesis rates for the acute, delayed, and overall study periods were 97% (35/36), 94% (34/36), and 92% (33/36), respectively. Treatment was well tolerated. CONCLUSIONS: The combination of aprepitant, dexamethasone, and palonosetron prevented emesis in more than 90% of breast cancer patients receiving their initial cycle of AC chemotherapy. Nausea was less well controlled. Overall complete response was achieved in one half of the study patients. Further improvement in the prevention of AC-induced chemotherapy induced nausea and vomiting will require more effective antinausea treatments. PMID- 22089430 TI - The unfulfilled promise: a systematic review of interventions to reduce the unmet supportive care needs of cancer patients. AB - PURPOSE: This review aimed to examine (a) trends in the number of publications on unmet needs over time and (b) the effectiveness of interventions designed to reduce unmet needs among cancer patients. METHODS: An electronic literature search of Medline to explore trends in the number of publications on patients' unmet needs and an additional literature search of Medline, CINAHL, PsychINFO, and Web of Science databases to identify methodologically rigorous research trials that evaluated interventions to reduce unmet needs were conducted. RESULTS: Publications per year on unmet needs have increased over time, with most being on descriptive research. Nine relevant trials were identified. Six trials reported no intervention effect. Three trials reported that intervention participants had a lower number of unmet needs or lower unmet needs score, compared to control participants. Of these, one study found that the intervention group had fewer supportive care needs and lower mean depression scores; one study found that intervention participants with high problem-solving skills had fewer unmet needs at follow-up; and one study found an effect in favor of the intervention group on psychological need subscale scores. CONCLUSIONS: Reasons for varying results across trials and the limited effectiveness of unmet needs interventions are more broadly discussed. These include inadequacies in psychometric rigor, problems with scoring methods, the use of ineffective interventions, and lack of adherence to intervention protocols. PMID- 22089431 TI - [Abstracts of the 35th Autumn Conference of the German Society of Cardiology and the 22nd Annual Conference of the Working Group for Cardiac Pacemakers and Arrhythmia. October 7-9, 2011 Nuremberg, Germany]. PMID- 22089433 TI - Chronic noncommunicable diseases and HIV-AIDS on a collision course: relevance for health care delivery, particularly in low-resource settings--insights from South Africa. AB - Sub-Saharan Africa is experiencing a multiple disease burden. Noncommunicable diseases (NCDs) are emerging, and their risk factors are becoming more common as lifestyles change and rates of urbanization increase. Simultaneously, epidemics of infectious diseases persist, and HIV/AIDS has taken hold in the region, although recent data indicate a decrease in new HIV infection rates. With the use of diabetes as a marker for NCDs, it was estimated that the number of people with diabetes would rise between 2000 and 2010 despite the HIV/AIDS epidemic, largely because of the aging of the population and the increase in risk factors for diabetes in South Africa. These numbers are likely to increase further, given the declining HIV/AIDS mortality rates and longer life expectancy due to the up scaling of antiretroviral therapy (ART), with its concomitant metabolic complications. Given that treated HIV/AIDS has become a chronic disease, and the health care needs of people on ART resemble those of people with NCDs, and given that vertical programs are difficult to sustain when health systems are underresourced and strained, there is a powerful argument to integrate the primary level care for people with chronic diseases, whether they be NCDs or infectious diseases. Pilot studies are required to test the feasibility of an integrated service that extends from health facilities into the community in a reciprocal manner based on the WHO Innovative Care for Chronic Conditions model of care. These will begin to provide the evidence that policy makers need to change the mode of health care delivery. PMID- 22089435 TI - Sex-specific differences in essential fatty acid metabolism. AB - Sex hormones may influence the enzymatic synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), which may lead to sex-specific differences in LC-PUFA status. Isotope studies with U-(13)C alpha-linolenic acid (ALA) have shown a considerably higher conversion rate of ALA to n-3 (omega-3) LC-PUFAs in women than in men. A review of the literature generally suggested that there was a higher contribution of arachidonic acid (AA) and docosahexaenoic acid (DHA) in blood lipids in women than in men; however, sex-specific differences were not seen in every study. The fatty acid composition of plasma phospholipids was recently reported separately for a large group of women and men (n > 3000) living in 15 regions of Europe. The contributions of saturated and monounsaturated fatty acids were higher, whereas those of AA and DHA were lower in men than in women; however, sex explained only ~ 2% of the variability of plasma phospholipid DHA values. Results reported from a limited number of randomized controlled trials of perinatal LC-PUFA supplementation have, on occasion, shown sex-specific differences in some outcomes; however, the heterogeneity both in the interventions and outcomes measured made it difficult to draw conclusions on the direction or the extent of the effects. Data summarized in the current review highlight the importance of planning a subgroup analysis by sex in perinatal LC PUFA supplementation trials. PMID- 22089434 TI - Conceptual framework for understanding the bidirectional links between food insecurity and HIV/AIDS. AB - Food insecurity, which affects >1 billion people worldwide, is inextricably linked to the HIV epidemic. We present a conceptual framework of the multiple pathways through which food insecurity and HIV/AIDS may be linked at the community, household, and individual levels. Whereas the mechanisms through which HIV/AIDS can cause food insecurity have been fairly well elucidated, the ways in which food insecurity can lead to HIV are less well understood. We argue that there are nutritional, mental health, and behavioral pathways through which food insecurity leads to HIV acquisition and disease progression. Specifically, food insecurity can lead to macronutrient and micronutrient deficiencies, which can affect both vertical and horizontal transmission of HIV, and can also contribute to immunologic decline and increased morbidity and mortality among those already infected. Food insecurity can have mental health consequences, such as depression and increased drug abuse, which, in turn, contribute to HIV transmission risk and incomplete HIV viral load suppression, increased probability of AIDS-defining illness, and AIDS-related mortality among HIV-infected individuals. As a result of the inability to procure food in socially or personally acceptable ways, food insecurity also contributes to risky sexual practices and enhanced HIV transmission, as well as to antiretroviral therapy nonadherence, treatment interruptions, and missed clinic visits, which are strong determinants of worse HIV health outcomes. More research on the relative importance of each of these pathways is warranted because effective interventions to reduce food insecurity and HIV depend on a rigorous understanding of these multifaceted relationships. PMID- 22089437 TI - Severe malnutrition and metabolic complications of HIV-infected children in the antiretroviral era: clinical care and management in resource-limited settings. AB - More than 2 million children globally are living with HIV infection and >90% of these reside in sub-Saharan Africa. Severe acute malnutrition (SAM) remains a major problem for HIV-infected children who live in resource-limited settings (RLS), and SAM is an important risk factor for mortality. SAM in HIV-infected children is associated with complications including electrolyte disorders, micronutrient deficiencies, and severe infections, which contribute to the high mortality. Access to antiretroviral therapy (ART) has significantly improved the survival of HIV-infected children, although the response to ART of children with SAM remains undocumented in the literature. Immune and virologic responses to ART in RLS are similar to those of infected children in resource-rich settings, but delays in initiation of therapy have led to a high early mortality. Antiretroviral drug toxicities have been described in children who receive therapy and may affect their quality of life and long-term survival. Metabolic complications of ART include lipodystrophy, dyslipidemia, lactic acidosis, insulin resistance, and osteopenia. These complications have been well described in adults and children from developed countries, but data from RLS are limited, and these complications may be compounded by SAM. In this article we review the epidemiology, clinical presentation, and complications of SAM in HIV-infected children and the metabolic complications of HIV-infected children in the era of ART, and discuss future research priorities for RLS. PMID- 22089436 TI - Developmental exposure to endocrine-disrupting chemicals programs for reproductive tract alterations and obesity later in life. AB - Many chemicals in the environment, especially those with estrogenic activity, are able to disrupt the programming of endocrine signaling pathways established during development; these chemicals are referred to as endocrine-disrupting chemicals. Altered programming can result in numerous adverse consequences in estrogen-target tissues, some of which may not be apparent until later in life. For example, a wide variety of structural, functional, and cellular effects have been identified in reproductive tract tissues. In addition to well-documented reproductive changes, obesity and diabetes have joined the list of adverse effects that have been associated with developmental exposure to environmental estrogens and other endocrine-disrupting chemicals. Obesity is a significant public health problem reaching epidemic proportions worldwide. Experimental animal studies document an association of developmental exposure to environmental estrogens and obesity. For example, a murine model of perinatal exposure to diethylstilbestrol has proven useful in studying mechanisms involved in abnormal programming of differentiating estrogen-target tissues, including reproductive tract tissues and adipocytes. Other environmental estrogens, including the environmental contaminant bisphenol A, have also been linked to reproductive problems and obesity later in life. Epidemiology studies support similar findings in humans, as do studies of cells in culture. Together, these findings suggest new targets for abnormal programming by estrogenic chemicals and provide evidence supporting the scientific concept termed the developmental origins of adult disease. Furthermore, the association of environmental estrogens with obesity and diabetes expands the focus on these diseases from intervention or treatment to include prevention or avoidance of chemical modifiers, especially during critical windows of development. PMID- 22089438 TI - Executive summary--nutritional care of HIV-infected adolescents and adults, including pregnant and lactating women: what do we know, what can we do, and where do we go from here? AB - The HIV pandemic continues to place an unbearable burden on the international community, with disease prevalence remaining highest in resource-limited settings in Africa, Asia, and the Americas. HIV is most often imposed on conditions of food insecurity and consequent malnutrition, poor sanitation, and chronic exposure to a myriad of infectious (eg, malaria, tuberculosis, and diarrheal) and noncommunicable (eg, obesity, diabetes, cancer, and cardiovascular) diseases. Women and children continue to bear the greatest burden. Two essential tenets underpin our approach to HIV: 1) antiretroviral drugs (ARVs) are essential to prolong lives and to halt the spread of HIV and AIDS and 2) food and sound nutrition are essential to human health. The challenge is to apply sound principles of clinical care and nutrition science to the safe and efficacious implementation of ARVs and for long-term care for people living with HIV and AIDS. The WHO has played a leading role in developing guidelines to support this goal with the generation of general recommendations regarding nutritional needs of people living with HIV and AIDS and specific guidelines for the nutritional care of HIV-infected infants and children (<14 y of age). These proceedings represent a summary of the work accomplished at a workshop sponsored by the NIH to review the existing evidence to support changes in the recommendations regarding nutrient requirements for people living with HIV and AIDS; to support development of new WHO guidelines for adolescents and adults, including for pregnant and lactating women; and to identify a research agenda to address outstanding knowledge gaps. PMID- 22089439 TI - Nutrition and disease progression pre-highly active antiretroviral therapy (HAART) and post-HAART: can good nutrition delay time to HAART and affect response to HAART? AB - Several studies have investigated a variety of nutritional supplementation interventions in adults with HIV. In this narrative review, we summarize the evidence from 31 clinical trials that explore clinical benefits of macronutrient and micronutrient supplementation in this population while attempting to answer the question of whether good nutrition can delay the time to highly active antiretroviral therapy (HAART) initiation and response. We focused on trials published in English between 1990 and 2010 that reported on CD4 count, viral load, and disease progression or survival. Among 9 macronutrient and 22 micronutrient trials, we found that evidence for improved CD4 count and HIV viral load with nutritional supplementation was limited; only 11.1% and 36.8% of macronutrient and micronutrient supplementation trials, respectively, reported improved CD4 count; and 33.3% and 12.5% of macronutrient and micronutrient trials, respectively, reported decreased viral load. Given their utility as surrogate markers of HIV disease progression, this suggests limited evidence for nutritional interventions having an impact on delaying HAART initiation or on improving HAART response. However, there are challenges in evaluating the effects of nutritional supplementation on clinical disease in that comparisons are difficult due to heterogeneity in study design, patient population, nutrient doses and combinations, baseline levels of deficiency, and study endpoints, including lack of clarity in defining and reporting HAART status. Future studies need to adopt a more rigorous standard design with adequate power and follow-up and require a consensus on composition and dose of nutrient interventions to be tested to more specifically answer the question on the impact of nutritional interventions on HIV disease progression and HAART response. PMID- 22089440 TI - Micronutrients in HIV/AIDS: is there evidence to change the WHO 2003 recommendations? AB - To establish whether there is new evidence to inform changes to WHO 2003 recommendations for micronutrient intake in persons with HIV/AIDS, we conducted a narrative review of the literature published from 2003 to 2010. Although the review focused on new randomized controlled trials of multiple micronutrients in HIV-infected adults, including pregnant and lactating women, we also considered randomized trials of single micronutrients. The review found that there are few published randomized controlled trials of micronutrients in HIV-infected persons and that most trials used high-dose multiple micronutrient supplementation. The trials were heterogeneous with respect to the composition and dose of micronutrients used and the target population studied. Despite this heterogeneity, 5 of 6 trials that used high-dose multiple micronutrients showed benefits in terms of either improved CD4 cell counts or survival. However, many of these trials were small and of short duration, and therefore the long-term risks and benefits of high-dose multiple micronutrients are not established. The current WHO recommendation for an intake of micronutrients at Recommended Dietary Allowance amounts continues to be a reasonable target for persons with clinically stable HIV infection. In light of new data that show adverse effects of high-dose vitamin A, the current recommendation for a single high dose of vitamin A in HIV infected women within 6 wk of delivery should be reviewed. PMID- 22089441 TI - Determinants of children's eating behavior. AB - Parents have a high degree of control over the environments and experiences of their children. Food preferences are shaped by a combination of genetic and environmental factors. This article is a review of current data on effective determinants of children's eating habits. The development of children's food preferences involves a complex interplay of genetic, familial, and environmental factors. There is evidence of a strong genetic influence on appetite traits in children, but environment plays an important role in modeling children's eating behaviors. Parents use a variety of strategies to influence children's eating habits, some of which are counterproductive. Overcontrol, restriction, pressure to eat, and a promise of rewards have negative effects on children's food acceptance. Parents' food preferences and eating behaviors provide an opportunity to model good eating habits. Satiety is closely related to diet composition, and foods with low energy density contribute to prevent overeating. Parents should be informed about the consequences of an unhealthy diet and lifestyle and motivated to change their nutritional habits. Parents should be the target of prevention programs because children model themselves on their parents' eating behaviors, lifestyles, eating-related attitudes, and dissatisfaction regarding body image. Pediatricians can have an important role in the prevention of diet-related diseases. Informed and motivated parents can become a model for children by offering a healthy, high-satiety, low-energy-dense diet and promoting self regulation from the first years of life. PMID- 22089442 TI - Nutritional and metabolic correlates of cardiovascular and bone disease in HIV infected patients. AB - The treatment of HIV infection has dramatically reduced the incidence of AIDS related illnesses. At the same time, non-AIDS-related illnesses such as cardiovascular and bone disease are becoming more prevalent in this population. The mechanisms of these illnesses are complex and are related in part to the HIV virus, antiretroviral medications prescribed for HIV infection, traditional risk factors exacerbated by HIV, and lifestyle and nutritional factors. Further prospective research is needed to clarify the mechanisms by which HIV, antiretroviral medications, and nutritional abnormalities contribute to bone and cardiovascular disease in the HIV population. Increasingly, it is being recognized that optimizing the treatment of HIV infection to improve immune function and reduce viral load may also benefit the development of non-AIDS related illnesses such as cardiovascular and bone disease. PMID- 22089443 TI - Energy expenditure in HIV infection. AB - Energy intake recommendations for adults should be based preferably on direct measurements of total daily energy expenditure (TDEE) in corresponding populations who are maintaining healthy body weight and satisfactory physical activity levels. During adolescence, pregnancy, and lactation, energy requirements should be based on TDEE plus the additional energy required to advance these physiologic states. With illness, energy expenditure and energy intake change, but nutritional intervention is not necessarily beneficial. This article reviews data on energy expenditure in HIV infection with a focus on adults, adolescents aged >=14 y, and pregnant and lactating women. Resting energy expenditure (REE) in adults with untreated asymptomatic HIV is ~ 10% higher than in healthy control subjects. In asymptomatic adults receiving antiretroviral therapy, REE may be similarly increased. HIV wasting and secondary infections are also associated with increased REE. In contrast, TDEE is typically normal in asymptomatic HIV and decreased in HIV wasting and secondary infection. No direct measurements of REE or TDEE are available in adolescents or in pregnant or lactating women with HIV. On the basis of current data, energy intake may need to increase by ~ 10% in adults with asymptomatic HIV to maintain body weight. In adolescents and in pregnant and lactating women with asymptomatic HIV, energy requirements should approximate recommendations for their uninfected counterparts until further data are available. In the resource-rich world, the energy expenditure changes associated with HIV are unlikely to contribute to significant weight loss. More data are needed on energy expenditure in HIV-infected populations from developing nations, where concurrent malnutrition and coinfections are common. PMID- 22089444 TI - Programming research: where are we and where do we go from here? AB - Convincing evidence has accumulated to show that both pre- and postnatal nutrition preprogram long-term health, well-being, and performance until adulthood and old age. There is a very large potential in the application of this knowledge to promote public health. One of the prerequisites for translational application is to strengthen the scientific evidence. More extensive knowledge is needed (eg, on effect sizes of early life programming in contemporary populations, on specific nutritional exposures, on sensitive time periods in early life, on precise underlying mechanisms, and on potential effect differences in subgroups characterized by, eg, genetic predisposition or sex). Future programming research should aim at filling the existing gaps in scientific knowledge, consider the entire lifespan, address socioeconomic issues, and foster innovation. Research should aim at results suitable for translational application (eg, by leading to health-promoting policies and evidence-based dietary recommendations in the perinatal period). International collaboration and a close research partnership of academia, industry, and small and medium enterprises may strengthen research and innovative potential enhancing the likelihood of translational application. The scientific know-how and methodology available today allow us to take major steps forward in the near future; hence, research on nutritional programming deserves high priority. PMID- 22089445 TI - Nutrition and pharmacology: general principles and implications for HIV. AB - Food and nutrition play an intimate and inextricable role in all aspects of drug metabolism, safety, and effectiveness. Antiretroviral therapies (ART) have assumed a preeminent position in the prevention, care, and treatment of HIV and its comorbidities. The interaction between food, nutrition, and ART has become an expanding area of interest both in terms of clinical standards of care and as a target for research. Since the original review of this topic by the WHO in 2005, much has been learned (8). This article contains a review of what is known about the general relationships between nutrition and pharmacology, as well as issues specific to ART, with particular attention to their use in low- and middle resource settings. The importance of food and nutrition on the bioavailability of drugs and vice versa has been an area of historical interest. However, much has been learned about the importance of nutritional status on drug metabolism, distribution, and effectiveness. The impact of traditional therapies (herbal/botanical) is highlighted as an area of clinical concern and one in need of further research. Additional attention is focused on the impact of individual micronutrients on drug pharmacokinetics and pharmacodynamics. Finally, attention is given to the nutritional implications of the metabolic consequences of ART, which include the potential impact of "colliding epidemics" of infection (eg, HIV, tuberculosis) and noncommunicable diseases. Much has been learned, but much remains to be accomplished to ensure the effective integration of nutritional considerations into the effective and safe use of ART. PMID- 22089446 TI - Sex differences in the endocrine system in response to protein intake early in life. AB - BACKGROUND: Nutritional factors during a sensitive period can influence child development in a sex-related manner. OBJECTIVE: Our aim was to investigate whether sex modulates the responses of relevant biochemical parameters and growth to different protein intakes early in life. DESIGN: In a randomized controlled trial, formula-fed infants were assigned to receive formula with higher protein (HP) or lower protein (LP) content. The main outcome measures were insulin-like growth factor (IGF)-1 axis parameters, weight, length, BMI, leptin, and C peptide/creatinine ratio at 6 mo of age. Dietary intake during the first 6 mo of life was also assessed. RESULTS: The IGF-1 axis response to HP feeding was modulated by sex. Total and free IGF-1 and IGF binding protein 3 concentrations were higher in girls than in boys. Compared with the LP diet, the HP diet was associated with higher IGF-1 and lower IGF binding protein 2 secretion. The response to this HP content formula tended to be stronger in girls than in boys. The HP diet was associated with a higher C-peptide/creatinine ratio. The leptin concentration was higher in girls than in boys and was correlated to the IGF-1 axis parameters. No interaction between sex and nutritional intervention was shown on growth. CONCLUSIONS: Our findings show that the endocrine response to a high protein diet early in life may be modulated by sex. The IGF-1 axis of female infants shows a stronger response to the nutritional intervention than does that of male infants, but there is no enhanced effect on growth. This trial was registered at clinicaltrials.gov as NCT00338689. PMID- 22089447 TI - Food insecurity: special considerations for women. AB - Food security exists when all people, at all times, have physical, social, and economic access to sufficient, safe, and nutritious food that meets their dietary needs and food preferences for an active and healthy life. Food insecurity is the converse state, is often associated with poverty and low income, and has important implications for the health and nutrition of individuals. Given their contribution to food production and preparation, their role in society as child bearers and caregivers, the increasing number of female-headed households worldwide, and their disproportionately poor economic status, women need special consideration in discussions of food insecurity and its effect on health, nutrition, and behavior. This article reviews the scientific literature on issues related to women and food insecurity. Food insecurity is associated with obesity, anxiety, and depressive symptoms; risky sexual behavior; poor coping strategies; and negative pregnancy outcomes in women, although evidence about the direction and causality of associations is unclear. There is a lack of evidence and understanding of the effects of food insecurity in resource-poor settings, including its effect on weight, nutritional outcomes, and pregnancy outcomes, as well as its effect on progression of diseases such as HIV infection. More research is needed to guide efficient interventions that address food insecurity among women. However, practical experience suggests that both short-term assistance and longer-term strategies that improve livelihoods, address behavioral and coping strategies, acknowledge the mental health components of food insecurity, and attempt to ensure that women have the same economic opportunities, access to land, and economic power as men are important. PMID- 22089448 TI - Metabolism and nutrition before and during pregnancy and after birth exert lasting effects on physiology, function, health, and performance well into adulthood and old age. Preface. PMID- 22089449 TI - Biomarker-based early cancer detection: is it achievable? AB - A new mathematical model evaluates the power of blood-based biomarkers for early cancer detection. PMID- 22089450 TI - Targeting chaperone-mediated autophagy in cancer. AB - A study in this issue of Science Translational Medicine provides fresh insight into the role of autophagy in cancer. Kon et al. show that a specific type of autophagy, called chaperone-mediated autophagy (CMA), is consistently elevated in tumors and is required for optimal tumor growth and metastasis. Selective inhibition of CMA slows tumor growth, boosts tumor cell death, and induces the regression of existing tumors. This work provides a rationale for further exploring manipulation of the CMA pathway as a strategy for treating cancer. PMID- 22089451 TI - Treatment and prevention of urinary tract infection with orally active FimH inhibitors. AB - Chronic and recurrent urinary tract infections pose a serious medical problem because there are few effective treatment options. Patients with chronic urinary tract infections are commonly treated with long-term prophylactic antibiotics that promote the development of antibiotic-resistant forms of uropathogenic Escherichia coli (UPEC), further complicating treatment. We developed small molecular weight compounds termed mannosides that specifically inhibit the FimH type 1 pilus lectin of UPEC, which mediates bacterial colonization, invasion, and formation of recalcitrant intracellular bacterial communities in the bladder epithelium. Here, we optimized these compounds for oral bioavailability and demonstrated their fast-acting efficacy in treating chronic urinary tract infections in a preclinical murine model. These compounds also prevented infection in vivo when given prophylactically and strongly potentiated the activity of the current standard of care therapy, trimethoprim-sulfamethoxazole, against clinically resistant PBC-1 UPEC bacteria. These compounds have therapeutic efficacy after oral administration for the treatment of established urinary tract infections in vivo. Their unique mechanism of action-targeting the pilus tip adhesin FimH-circumvents the conventional requirement for drug penetration of the outer membrane, minimizing the potential for the development of resistance. The small-molecular weight compounds described herein promise to provide substantial benefit to women suffering from chronic and recurrent urinary tract infections. PMID- 22089452 TI - Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. AB - Most clinical blood biomarkers lack the necessary sensitivity and specificity to reliably detect cancer at an early stage, when it is best treatable. It is not yet clear how early a clinical blood assay can be used to detect cancer or how biomarker-based strategies can be improved to enable earlier detection of smaller tumors. To address these issues, we developed a mathematical model describing dynamic plasma biomarker kinetics in relation to the growth of a tumor, beginning with a single cancer cell. To exemplify a realistic scenario in which biomarker is shed by both cancerous and noncancerous cells, we primed the model on ovarian tumor growth and CA125 shedding data, for which tumor growth parameters and shedding rates are readily available in published literature. We found that a tumor could grow unnoticed for more than 10.1 years and reach a volume of about pi/6(25.36 mm)(3), corresponding to a spherical diameter of about 25.36 mm, before becoming detectable by current clinical blood assays. Model parameters were perturbed over log orders of magnitude to quantify ideal shedding rates and identify other blood-based strategies required for early submillimeter tumor detectability. The detection times we estimated are consistent with recently published tumor progression time lines based on clinical genomic sequencing data for several cancers. Here, we rigorously showed that shedding rates of current clinical blood biomarkers are likely 10(4)-fold too low to enable detection of a developing tumor within the first decade of tumor growth. The model presented here can be extended to virtually any solid cancer and associated biomarkers. PMID- 22089453 TI - Chaperone-mediated autophagy is required for tumor growth. AB - The cellular process of autophagy (literally "self-eating") is important for maintaining the homeostasis and bioenergetics of mammalian cells. Two of the best studied mechanisms of autophagy are macroautophagy and chaperone-mediated autophagy (CMA). Changes in macroautophagy activity have been described in cancer cells and in solid tumors, and inhibition of macroautophagy promotes tumorigenesis. Because normal cells respond to inhibition of macroautophagy by up regulation of the CMA pathway, we aimed to characterize the CMA status in different cancer cells and to determine the contribution of changes in CMA to tumorigenesis. Here, we show consistent up-regulation of CMA in different types of cancer cells regardless of the status of macroautophagy. We also demonstrate an increase in CMA components in human cancers of different types and origins. CMA is required for cancer cell proliferation in vitro because it contributes to the maintenance of the metabolic alterations characteristic of malignant cells. Using human lung cancer xenografts in mice, we confirmed the CMA dependence of cancer cells in vivo. Inhibition of CMA delays xenograft tumor growth, reduces the number of cancer metastases, and induces regression of existing human lung cancer xenografts in mice. The fact that similar manipulations of CMA also reduce tumor growth of two different melanoma cell lines suggests that targeting this autophagic pathway may have broad antitumorigenic potential. PMID- 22089454 TI - ANKH and susceptibility to and severity of ankylosing spondylitis. AB - OBJECTIVE: Unconfirmed reports describe association of ankylosing spondylitis (AS) with several candidate genes including ANKH. Cellular export of inorganic pyrophosphate is regulated by the ANK protein, and mutant mice (ank/ank), which have a premature stop codon in the 3' end of the ank gene, develop severe ankylosis. We tested the association between single-nucleotide polymorphisms (SNP) in these genes and susceptibility to AS in a population of patients with AS. We investigated the role of these genes in terms of functional (BASFI) and metrological (BASMI) measures, and the association with radiological severity (mSASSS). METHODS: Our study was conducted on 355 patients with AS and 95 ethnically matched healthy controls. AS was defined according to the modified New York criteria. Four SNP in ANKH (rs27356, rs26307, rs25957, and rs28006) were genotyped. Association analysis was performed using Cochrane-Armitage and linear regression tests for dichotomous and quantitative variables. Analyses of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASFI, and mSASSS were controlled for sex and disease duration. RESULTS: None of the 4 markers showed significant single-locus disease associations (p > 0.05), suggesting that ANKH was not a major determinant of AS susceptibility in our population. No association was observed between these SNP and age at symptom onset, BASDAI, BASFI, BASMI, or mSASSS. CONCLUSION: These results confirm data in white Europeans that ANKH is probably not a major determinant of susceptibility to AS. ANKH polymorphisms do not markedly influence AS disease severity, as measured by BASMI and mSASSS. PMID- 22089455 TI - Frequency of class III and IV nephritis in systemic lupus erythematosus without clinical renal involvement: an analysis of predictive measures. AB - OBJECTIVE: To determine the frequency of International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis in patients with systemic lupus erythematosus (SLE) without clinical renal involvement. METHODS: We investigated the renal pathology of 195 patients with SLE, including 86 patients without clinical renal involvement. RESULTS: Lupus nephritis other than class I was found in 58% of the patients without clinical renal involvement, and class III and IV nephritis was found in 15% of these patients. To reveal the predictive measures involved in class III or IV lupus nephritis, we explored the clinical measures in patients with SLE who did not have clinical renal involvement. Anti-dsDNA antibody titers were significantly higher (p = 0.0266) and C3 values were significantly lower (p = 0.0073) in patients with class III or IV lupus nephritis than in patients without class III or IV lupus nephritis. The sensitivity and specificity values were 77% and 73%, respectively, for cutoff levels of both 40 IU/ml for anti-dsDNA antibodies and 55 mg/dl for C3 (OR 8.8, p = 0.0011). CONCLUSION: The frequency of nephritis, including ISN/RPS class III and IV, was unexpectedly high in SLE patients without clinical renal involvement. ISN/RPS class III or IV lupus nephritis could be hidden in patients with SLE who present both a high titer of anti-dsDNA antibody and a low concentration of C3, even when they have clinically normal urinary findings and renal function. PMID- 22089456 TI - Glucosamine sulfate reduces prostaglandin E(2) production in osteoarthritic chondrocytes through inhibition of microsomal PGE synthase-1. AB - OBJECTIVE: Glucosamine sulfate (GS) has been inferred to have a potential antiinflammatory effect on osteoarthritis (OA). We investigated its effect on prostaglandin E(2) (PGE(2)) in human OA chondrocytes, and the level in the PGE(2) pathway at which its effect takes place. METHODS: We investigated the effect of GS treatment (0.05, 0.2, 1.0, and 2.0 mM) in OA chondrocytes in the absence or presence of interleukin 1beta (IL-1beta; 100 pg/ml). We determined the expression levels and protein production/activity of PGE(2), cyclooxygenase-1 (COX-1), COX 2, microsomal PGE synthase-1 (mPGES-1), glutathione, and peroxisome proliferator activated receptor-gamma (PPARgamma), using specific primers, antibodies, and assays. RESULTS: GS treatment at 1 and 2 mM significantly inhibited (p <= 0.03) production of endogenous and IL-1beta-induced PGE(2). GS in both the absence and presence of IL-1beta did not significantly modulate COX-1 protein production, but GS at 1 and 2 mM demonstrated a decrease in COX-2 glycosylation in that it reduced the molecular mass of COX-2 synthesis. Under IL-1beta stimulation, GS significantly inhibited mPGES-1 messenger RNA expression and synthesis at 1 and 2 mM (p <= 0.02) as well as the activity of glutathione (p <= 0.05) at 2 mM. Finally, in both the absence and presence of IL-1beta, PPARgamma was significantly induced by GS at 1 and 2 mM (p <= 0.03). CONCLUSION: Our data document the potential mode of action of GS in reducing the catabolism of OA cartilage. GS inhibits PGE(2) synthesis through reduction in the activity of COX 2 and the production and activity of mPGES-1. These findings may, in part, explain the mechanisms by which this drug exerts its positive effect on OA pathophysiology. PMID- 22089457 TI - Persistent fetal sinus bradycardia associated with maternal anti-SSA/Ro and anti SSB/La antibodies. AB - OBJECTIVE: To study the clinical course and outcome of fetal sinus bradycardia (SB) due to maternal antibody-induced sinus node dysfunction. METHODS: We reviewed the maternal, prenatal, and postnatal findings of fetuses with SB associated with elevated maternal anti-SSA/Ro and anti-SSB/La antibodies. RESULTS: Of the 6 cases diagnosed prenatally, 3 had isolated SB persisting after birth and had a good prognosis. Three fetuses with SB and severe myocardial involvement (congenital complete heart block and/or endocardial fibroelastosis) succumbed in utero in spite of treatment. Postmortem histopathology in 1 fetus showed inflammatory destruction of the sinus and atrioventricular nodes. SB was detected incidentally in a 7-year-old girl. She had intermittent heart block with progressive sinus arrest requiring permanent pacemaker. CONCLUSION: Fetal SB associated with maternal autoantibodies may persist in childhood, with a good prognosis in the absence of widespread cardiac involvement. PMID- 22089458 TI - Sex differences in response to anti-tumor necrosis factor therapy in early and established rheumatoid arthritis -- results from the DANBIO registry. AB - OBJECTIVE: To investigate sex differences in response to anti-tumor necrosis factor-alpha (TNF-alpha) therapy over time in early versus established rheumatoid arthritis (RA). METHODS: Patients with RA who initiated anti-TNF therapy between January 2003 and June 2008 in Denmark were selected from the DANBIO Registry. Sex differences in baseline disease features were examined using chi-square, Mann Whitney U tests, and t tests. Using a generalized estimating equations (GEE) model for repeated measures, we examined European League Against Rheumatism (EULAR) responses in men and women over 48 months of followup, adjusting for baseline values of age, 28-joint Disease Activity Score (DAS28), disease duration, and anti-TNF, methotrexate, and prednisolone use. RESULTS: At initiation of anti-TNF therapy (baseline), 328 women and 148 men had early RA (<= 2 yrs), and 1245 women and 408 men had established RA (> 2 yrs). In both early and established RA, men and women had active disease with similar DAS28 scores (mean +/- SD 5.2 +/- 1.1), physician global scores, swollen joint counts, and radiographic changes. In early RA, men were significantly more likely to achieve a EULAR good/moderate response over 48 months compared to women (GEE; p = 0.003), and a significant interaction between sex and followup time (GEE; p < 0.0005) suggested that men achieved this response sooner than women. CONCLUSION: Better responses to anti-TNF therapy among men compared to women in early but not established RA suggest that disease duration at initiation of therapy may be an important factor to consider when investigating sex differences in treatment responses. PMID- 22089459 TI - CAG repeat polymorphism in the androgen receptor gene in women with rheumatoid arthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA) is the most common chronic, autoimmune, inflammatory disease, with a genetic and hormonal background. The prevalence of women among patients with RA suggests the important role of sex hormones in the pathogenesis of RA. We examined the association between CAG repeat polymorphism in the androgen receptor (AR) gene and susceptibility to RA and its clinical features in white women. METHODS: The study groups consisted of 325 female patients with RA and 238 female controls. CAG repeat polymorphism was determined using polymerase chain reaction and subsequent fragment analysis by capillary electrophoresis. RESULTS: The number of CAG repeats in patients did not differ from that of controls (22.1 +/- 2.9 vs 21.9 +/- 2.9, respectively; p = 0.26), but the presence of articular erosions was associated with a lower number of repeats in the shorter allele of patients with RA (20.4 +/- 2.2 vs 21.2 +/- 2.4; p = 0.031). When alleles with < 22 CAG were classified as short (S) and those with >= 22 CAG as long (L), the age at diagnosis of RA was lower in women with S-S genotype in comparison to combined S-L + L-L genotypes (43.0 +/- 14.6 yrs vs 47.6 +/- 12.5 yrs; p = 0.021). In patients with the L-L genotype, the frequency of erosive disease (OR 0.45, 95% CI 0.25-0.80, p = 0.0085) and extraarticular manifestations (OR 0.50, 95% CI 0.26-0.98, p = 0.047) was lower in comparison to carriers of the S allele. In multivariate analysis, the L-L genotype was an independent factor associated with a lower risk of erosions (OR 0.44, 95% CI 0.22 0.90, p = 0.024). CONCLUSION: The results suggest the association of short AR (CAG)(n) alleles with earlier onset and a more aggressive course of RA. PMID- 22089460 TI - Usefulness of cellular text messaging for improving adherence among adolescents and young adults with systemic lupus erythematosus. AB - OBJECTIVE: In a cohort of 70 patients with childhood-onset systemic lupus erythematosus (cSLE): to determine the baseline adherence to medications and visits; to investigate the effects of cellular text messaging reminders (CTMR) on adherence to clinic visits; and to study the influence of CTMR on adherence to use of hydroxychloroquine (HCQ). METHODS: CTMR were sent to 70 patients prior to clinic visits for 14 months. A subgroup of patients were evaluated for medication adherence to HCQ: 19 patients receiving CTMR prior to each scheduled HCQ dose were compared to 22 patients randomized to standard of care education about HCQ. Visit adherence was measured using administrative databases. Pharmacy refill information, self-report of adherence, and HCQ blood levels were utilized to monitor medication adherence to HCQ. Sufficient adherence to visits or HCQ was defined as estimates > 80%. Disease activity was primarily monitored with the Systemic Lupus Erythematosus Disease Activity Index. RESULTS: At baseline, 32% of patients were sufficiently adherent to HCQ, and 81% to clinic visits. Visit adherence improved significantly by > 80% among those who were nonadherent to clinic visits at the baseline CTMR (p = 0.01). CTMR did not influence adherence to HCQ over time. CONCLUSION: Patients with cSLE were only modestly adherent to HCQ and clinic visits. CTMR may be effective for improving visit adherence among adolescents and young adults with cSLE, but it does not improve adherence to HCQ. PMID- 22089461 TI - Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension. AB - OBJECTIVE: To evaluate the safety and efficacy of civamide cream 0.075% for the treatment of osteoarthritis (OA) of the knee. METHODS: We conducted a 12-week, multicenter, randomized, double-blind study with a 52-week open-label extension. Patients with OA of the knee received either civamide cream 0.075% or a lower dose of civamide cream, 0.01%, as the control. The 3 co-primary endpoints in the double-blind study were the time-weighted average (TWA) of change from baseline to Day 84 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, the WOMAC physical function subscale, and the Subject Global Evaluation (SGE). In the 52-week open-label extension study, the Osteoarthritis Pain Score and SGE were assessed. RESULTS: A total of 695 patients were randomized to receive civamide cream 0.075% (n = 351) or civamide cream 0.01% (control; n = 344) in the double-blind study. Significance in favor of civamide cream 0.075% was achieved for the TWA for all 3 co-primary efficacy variables: WOMAC pain (p = 0.009), WOMAC physical function (p < 0.001), and SGE (p = 0.008); and at Day 84 for these 3 variables (p = 0.013, p < 0.001, and p = 0.049, respectively). These analyses accounted for significant baseline-by treatment interactions. In the 52-week open-label extension, efficacy was maintained. Civamide cream 0.075% was well tolerated throughout the studies. CONCLUSION: These studies demonstrate the efficacy of civamide cream for up to 1 year of continuous use. Civamide cream, with its lack of systemic absorption, does not have the potential for serious systemic toxicity, in contrast to several other OA treatments. PMID- 22089462 TI - Glucocorticoid: major factor for reduced immunogenicity of 2009 influenza A (H1N1) vaccine in patients with juvenile autoimmune rheumatic disease. AB - OBJECTIVE: To assess the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with juvenile autoimmune rheumatic disease (ARD) and healthy controls, because data are limited to the adult rheumatologic population. METHODS: A total of 237 patients with juvenile ARD [juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), juvenile scleroderma, and vasculitis] and 91 healthy controls were vaccinated. Serology for anti-H1N1 was performed by hemagglutination inhibition assay. Seroprotection rate, seroconversion rate, and factor-increase in geometric mean titer (GMT) were calculated. Adverse events were evaluated. RESULTS: Age was comparable in patients and controls (14.8 +/- 3.0 vs 14.6 +/- 3.7 years, respectively; p = 0.47). Three weeks after immunization, seroprotection rate (81.4% vs 95.6%; p = 0.0007), seroconversion rate (74.3 vs 95.6%; p < 0.0001), and the factor-increase in GMT (12.9 vs 20.3; p = 0.012) were significantly lower in patients with juvenile ARD versus controls. Subgroup analysis revealed reduced seroconversion rates in JSLE (p < 0.0001), JIA (p = 0.008), JDM (p = 0.025), and vasculitis (p = 0.017). Seroprotection (p < 0.0001) and GMT (p < 0.0001) were decreased only in JSLE. Glucocorticoid use and lymphopenia were associated with lower seroconversion rates (60.4 vs 82.9%; p = 0.0001; and 55.6 vs 77.2%; p = 0.012). Multivariate logistic regression including diseases, lymphopenia, glucocorticoid, and immunosuppressants demonstrated that only glucocorticoid use (p = 0.012) remained significant. CONCLUSION: This is the largest study to demonstrate a reduced but adequate immune response to H1N1 vaccine in patients with juvenile ARD. It identified current glucocorticoid use as the major factor for decreased antibody production. The short-term safety results support its routine recommendation for patients with juvenile ARD. ClinicalTrials.gov; NCT01151644. PMID- 22089463 TI - Maintenance of efficacy and safety with subcutaneous golimumab among patients with active rheumatoid arthritis who previously received intravenous golimumab. AB - OBJECTIVE: To evaluate the efficacy/safety of subcutaneous (SC) golimumab in patients with rheumatoid arthritis (RA) who previously received intravenous (IV) golimumab with or without methotrexate (MTX). METHODS: Adult patients with RA (n = 643) with persistent disease despite MTX (>= 15 mg/wk for >= 3 months) were randomized to IV placebo + MTX (n = 129) or IV golimumab 2-4 mg/kg (+/- MTX) every 12 weeks (n = 514). Patients who completed the study through Week 48 could participate in the longterm extension (LTE), comprising open-label golimumab 50 mg SC every 4 weeks (+/- MTX) for 24 weeks (LTE-0 to LTE-24) followed by 16 weeks of safety followup (LTE-24 to LTE-40; MTX could be adjusted). RESULTS: At Week 48, 28% (nominal p < 0.001 vs placebo), 11%, and 8% of patients who received IV golimumab + MTX, golimumab alone, and placebo + MTX, respectively, achieved >= 50% improvement in the American College of Rheumatology response criteria (ACR50). Among the 505 patients who entered the LTE and were still participating, the proportion of patients treated with golimumab 50 mg SC (+/- MTX) achieving an ACR50 response increased to 44% at both LTE-14 and LTE-24. ACR20, ACR70, and 28 joint Disease Activity Score using C-reactive protein exhibited similar response patterns as ACR50. Infections were the most commonly reported adverse events through the end of IV golimumab dosing (37% placebo + MTX, 45% golimumab, 51% golimumab + MTX) and with SC golimumab from LTE-0 through LTE-40 (35% golimumab, 36% golimumab + MTX). Concomitant MTX use yielded lower incidences of antibodies to SC golimumab and injection-related reactions. CONCLUSION: Clinical improvements observed in golimumab-treated patients were sustained or improved in patients switched from IV (2-4 mg/kg +/- MTX) to open-label SC (50 mg +/- MTX) golimumab. Both IV and SC golimumab demonstrated acceptable safety profiles (Clinicaltrials.gov NCT00361335). PMID- 22089464 TI - Pain thresholds in rheumatoid arthritis: the effect of tender point counts and disease duration. AB - OBJECTIVE: We evaluated the influence of demographic and clinical factors on pain thresholds in patients with rheumatoid arthritis (RA). METHODS: A cross-sectional observational study (105 patients with RA) assessed pain thresholds using an algometer. Regression analysis examined the influence of demographic and clinical assessments. RESULTS: Pain thresholds (median 289, interquartile range 89-434) correlated with assessments of disease activity (tender joint counts), disability (Health Assessment Questionnaire), fatigue, depression, and anxiety. Ordinal logistic regression showed tender point counts and disease duration were the dominant contributors. CONCLUSION: These findings suggest that low pain thresholds reflect "fibromyalgic" RA (many tender points) and central pain sensitization with prolonged disease duration. PMID- 22089465 TI - Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. AB - OBJECTIVE: To evaluate the efficacy compared to the relapse risk and tolerance of systematic rituximab (RTX) infusions as maintenance therapy for patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), who entered remission taking conventional immunosuppressants or RTX. METHODS: A retrospective study of the main clinical characteristics, outcomes, and RTX tolerance of patients who had received >= 2 RTX maintenance infusions in our center, regardless of induction regimen, between 2003 and 2010. RESULTS: We identified 28 patients [4 MPA and 24 GPA; median age 55.5 yrs (range 18-78); 17 (60%) males] who received a median of 4 (range 2-10) RTX maintenance infusions, with median followup of 38 months (range 21-97) since diagnosis or last flare. None experienced a RTX infusion-related adverse event; 15 patients (among the 21 with available data) had hypogammaglobulinemia (predominantly IgM) prior to their last RTX maintenance infusion; 3 had infectious events (1 cutaneous abscess, 1 otitis, 1 fatal H1N1 flu). Two patients suffered pulmonary relapses shortly before a planned RTX maintenance infusion (both had increased antineutrophil cytoplasmic antibody levels and 1 had CD19+ lymphocyte reconstitution). CONCLUSION: Rituximab maintenance therapy was well tolerated but did not completely prevent relapses and persistent "grumbling" disease. These preliminary results remain to be confirmed by a randomized controlled trial currently in progress. PMID- 22089466 TI - Mortality risk by functional status and health-related quality of life in patients with rheumatoid arthritis. AB - OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of death. Modern RA therapy has been shown to improve health status, but the relationship of such improvements to mortality risk is unknown. We assessed the relationship between health status and all-cause mortality in patients with RA, using the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study Short Form-36 questionnaire (SF-36) physical and mental component summary scores (PCS, MCS). METHODS: Subjects (n = 10,319) were selected from the National Data Bank for Rheumatic Diseases, a prospective longitudinal observational US study with semiannual assessments of HAQ, PCS, and MCS. Risk of death up to 7 years through 2006 was obtained from the US National Death Index. Relationship of HAQ, PCS, and MCS to mortality was assessed using Cox regression models; prediction accuracy was compared using Harrell's concordance coefficient (C). RESULTS: Over 64,888 patient-years of followup, there were 1317 deaths. Poorer baseline health status was associated with greater mortality risk. Adjusting for age, sex, and baseline PCS and MCS, declines in PCS and HAQ were associated with higher risk of death. HAQ improvement was associated with reduced mortality risk from 6 months through 3 years; a similar relationship was not observed for PCS or MCS improvement. Controlling for baseline values, change in PCS or HAQ did not improve prediction accuracy. CONCLUSION: The HAQ and the SF-36 PCS are similarly and strongly associated with mortality risk in patients with RA. Change in these measures over time does not appear to add to predictive accuracy over baseline levels. PMID- 22089467 TI - Proposed severity and response criteria for Routine Assessment of Patient Index Data (RAPID3): results for categories of disease activity and response criteria in abatacept clinical trials. AB - BACKGROUND: An index is needed to assess the status of patients with rheumatoid arthritis (RA), as none of the existing measures are applicable to all individual patients. The 28-joint Disease Activity Score (DAS28) is the most specific and widely used index. Routine Assessment of Patient Index Data (RAPID3) is an index containing only the 3 patient self-report core dataset measures, without a laboratory test or formal joint count, and with simple scoring. RAPID3 is correlated significantly with DAS28, but calculated in 5-10 seconds on a Multidimensional Health Assessment Questionnaire (MDHAQ), compared to 114 seconds for DAS28. METHODS: DAS28 (0-10 scale) categories for high, moderate, and low activity, and remission (<= 2.6, 2.6-3.2, 3.21-5.1, and > 5.1, respectively) and proposed RAPID3 (0-30 scale) categories for severity (0 <= 3, 3.1-6, 6.1-12, and > 12) were compared in patients taking abatacept and control-treated patients at the endpoint of the Abatacept in Inadequate Response to Methotrexate (AIM) and the Abatacept Trial in Treatment of Anti-TNF INadequate Responders (ATTAIN) clinical trials, using cross-tabulations and kappa statistics. RESULTS: Overall, 92%-99% of patients classified as having high DAS28 activity had high or moderate RAPID3 severity, while 64%-83% in DAS28 remission had RAPID3 low severity or remission; 50%-82% of patients with good or poor EULAR responses had good or poor RAPID3 responses. Kappa values ranged from 0.25 to 0.48, and weighted kappas from 0.32 to 0.52, indicating fair to moderate agreement for the 2 indices. CONCLUSION: Proposed RAPID3 severity and response categories yield comparable results to DAS28 and EULAR criteria in AIM and ATTAIN. DAS28 is more specific for clinical trials. RAPID3 does not preclude also scoring DAS28, and may be informative in the infrastructure of routine care. PMID- 22089468 TI - Clinical significance of Cryofibrinogenemia: possible pathophysiological link with Raynaud's phenomenon. AB - OBJECTIVE: To describe the clinical findings and prevalence of patients with cryofibrinogenemia (CF) and to determine whether CF is associated with primary Raynaud's phenomenon. METHODS: Between June 2006 and December 2009, 227 patients were tested for CF in a single university hospital. Forty-five patients with primary Raynaud's phenomenon were tested for CF. RESULTS: A total of 117 patients with CF without cryoglobulinemia were included. The main clinical manifestations included skin manifestations (50%) and arthralgia (35%). There were 67 patients with primary CF and 50 patients with secondary CF. There was no significant difference in the mean concentration of the cryoprecipitate in primary CF as compared to the secondary form (172 +/- 18.6 vs 192 +/- 20.9 mg/dl, respectively; p = 0.41). Highest concentrations of cryoprecipitate were observed in those containing fibrinogen only as compared to cryoprecipitates containing fibrinogen and fibronectin (301 +/- 43.5 vs 125 +/- 10.6 mg/dl; p < 0.001). Patients having skin necrosis (n = 3) had significantly higher values of cryofibrinogen compared to those without necrosis (638 +/- 105 vs 160 +/- 10.2 mg/dl; p = 0.0046). Among the 45 patients with primary Raynaud's phenomenon, 36 had associated CF. There was no significant difference in the mean concentration of the cryoprecipitate in these patients compared to those with primary CF. CONCLUSION: There seems to be a significant correlation between cryofibrinogen concentration and the severity of the clinical signs, particularly when cryoprecipitate is composed of fibrinogen alone. CF might have a possible pathophysiological role in primary Raynaud's phenomenon. PMID- 22089469 TI - The ClASsification for Psoriatic ARthritis (CASPAR) criteria--a retrospective feasibility, sensitivity, and specificity study. AB - OBJECTIVE: To evaluate the sensitivity, specificity, and feasibility of the ClASsification criteria for Psoriatic ARthritis (CASPAR) to retrospectively classify an existing research cohort. METHODS: In total, 480 patient records were reviewed from the Royal National Hospital for Rheumatic Diseases Psoriatic Arthritis (PsA) cohort and for 100 consecutive controls with inflammatory arthritis from a general rheumatology clinic. The CASPAR score was modified for retrospective use; both "inflammation" and "current psoriasis" were recorded as present if they had ever been confirmed in the rheumatology clinic. Sensitivity and specificity of the CASPAR criteria were compared with expert clinical diagnosis. RESULTS: A total of 480 database records were identified. Nine sets of records had been lost or destroyed. The diagnoses had changed in 15 cases, which were transferred to the control arm, leaving 456 patients with an expert diagnosis of PsA. Of 115 controls, 96 had rheumatoid arthritis, 5 osteoarthritis, 3 reactive arthritis, 3 seronegative arthritis, 3 undifferentiated arthralgia, 2 ankylosing spondylitis, 1 spondyloarthritis, and 2 systemic sclerosis. Sensitivity (99.7%) and specificity (99.1%) were both high and equivalent to previous reports. Sensitivity remained high even after inclusion of 7 PsA patients with insufficient data to complete the CASPAR assessment (sensitivity 98.2%, specificity 99.1%). The criteria were found to be easy and practical to apply to case records. CONCLUSION: Our study demonstrates that the feasibility, specificity, and sensitivity of the CASPAR are maintained when adapted for retrospective use to classify an established research cohort. PMID- 22089470 TI - Attainment of inactive disease status following initiation of TNF-alpha inhibitor therapy for juvenile idiopathic arthritis: enthesitis-related arthritis predicts persistent active disease. AB - OBJECTIVE: To analyze the attainment of inactive disease following initiation of tumor necrosis factor-alpha (TNF-alpha) inhibitors in a heterogeneous cohort of children with juvenile idiopathic arthritis (JIA). METHODS: We performed retrospective chart review of all children with JIA at 1 academic center who had started TNF-alpha inhibitor therapy. We retrospectively determined inactive disease status according to the 2004 criteria of Wallace, et al. We evaluated inactive disease status at 1 year after initiation of TNF-alpha inhibitor and attainment of inactive disease at any point during the study period. Predictors of inactive disease were determined using univariate analyses and multivariable logistic regression models. RESULTS: A total of 125 patients started TNF-alpha inhibitors, and 88 patients had data available for the 1-year followup visit. Many patients (49%) started TNF-alpha inhibitors within 6 months of the diagnosis of JIA. Diverse JIA phenotypes were represented: at baseline, 29% of all patients had active enthesitis and only 23% had active polyarthritis. At the 1-year followup, 36 of 88 (41%) patients had inactive disease. Overall, 67 of 125 (54%) patients ever attained inactive disease status during the study period. In multivariable models, enthesitis-related arthritis (ERA) and higher Childhood Health Assessment Questionnaire (CHAQ) scores at baseline were independently associated with failure to later attain inactive disease status. CONCLUSION: Treatment with TNF-alpha inhibitors appears to be less effective for attaining inactive disease status in patients with ERA or higher baseline CHAQ scores. Further studies are needed regarding the clinical effectiveness of TNF-alpha inhibitor therapy and the optimal treatment of ERA. PMID- 22089471 TI - Real-time DNA detection using Pt nanoparticle-decorated reduced graphene oxide field-effect transistors. AB - A large-area, continuous, few-layer reduced graphene oxide (rGO) thin film has been fabricated on a Si/SiO(2) wafer using the Langmuir-Blodgett (LB) method followed by thermal reduction. After photochemical reduction of Pt nanoparticles (PtNPs) on rGO, the obtained PtNPs/rGO composite is employed as the conductive channel in a solution-gated field effect transistor (FET), which is then used for real-time detection of hybridization of single-stranded DNA (ssDNA) with high sensitivity (2.4 nM). Such a simple, but effective method for fabrication of rGO based transistors shows great potential for mass-production of graphene-based electronic biosensors. PMID- 22089472 TI - Polymorphisms in the human ALOX12 and ALOX15 genes are associated with peak bone mineral density in Chinese nuclear families. AB - SUMMARY: Association between ten single-nucleotide polymorphisms (SNPs) in the human ALOX12 and ALOX15 genes and variations in peak bone mineral density (BMD) in a large sample of Chinese nuclear families with female offspring using the quantitative transmission disequilibrium test (QTDT). Our results suggest that the genetic polymorphisms in both human ALOX12 and ALOX15 may contribute to variations in the peak BMD of Chinese women. INTRODUCTION: The aim of this study was to investigate whether polymorphisms in the human ALOX12 and ALOX15 genes are associated with variations in peak BMD in Chinese nuclear families with female offspring. METHODS: Each five SNPs in the ALOX12 and ALOX15 genes were genotyped in a total of 1,260 individuals from 401 Chinese nuclear families. The BMD of the lumbar spine, femoral neck and total hip was measured by dual-energy X-ray absorptiometry. We tested whether a single SNP or a haplotype was associated with peak BMD variations using the QTDT. RESULTS: Using QTDT to measure within-family associations in ALOX15, we observed a significant association between rs916055 and BMD in the lumbar spine (p = 0.027 in the permutation 1,000 test). However, in ALOX12, rs312470 was significantly associated with BMD in the femoral neck (p = 0.029 and p = 0.036 in the permutation 1,000 test). The results of a haplotype analysis supported the findings of the single locus test for ALOX15. CONCLUSIONS: Our results suggest that the genetic polymorphisms in both human ALOX12 and ALOX15 may contribute to variations in the peak BMD of Chinese women. PMID- 22089473 TI - Inferring synaptic inputs given a noisy voltage trace via sequential Monte Carlo methods. AB - We discuss methods for optimally inferring the synaptic inputs to an electrotonically compact neuron, given intracellular voltage-clamp or current clamp recordings from the postsynaptic cell. These methods are based on sequential Monte Carlo techniques ("particle filtering"). We demonstrate, on model data, that these methods can recover the time course of excitatory and inhibitory synaptic inputs accurately on a single trial. Depending on the observation noise level, no averaging over multiple trials may be required. However, excitatory inputs are consistently inferred more accurately than inhibitory inputs at physiological resting potentials, due to the stronger driving force associated with excitatory conductances. Once these synaptic input time courses are recovered, it becomes possible to fit (via tractable convex optimization techniques) models describing the relationship between the sensory stimulus and the observed synaptic input. We develop both parametric and nonparametric expectation-maximization (EM) algorithms that consist of alternating iterations between these synaptic recovery and model estimation steps. We employ a fast, robust convex optimization-based method to effectively initialize the filter; these fast methods may be of independent interest. The proposed methods could be applied to better understand the balance between excitation and inhibition in sensory processing in vivo. PMID- 22089474 TI - Attenuation of hypertension-mediated glomerulosclerosis in conjunction with increased angiotensin (1-7). AB - BACKGROUND: Controversy exists as to whether angiotensin (1-7) (Ang (1-7)) acts as a protective hormone against renal injury. METHODS: We compared the degree of improvement of hypertensive nephropathy following 8 weeks' treatment with either the angiotensin II receptor type 1 antagonist olmesartan medoxomil or the cardioselective beta blocker atenolol in 8-week-old spontaneously hypertensive rats (SHRs). RESULTS: Both treatment regimens reduced mean blood pressure in a similar fashion, while bradycardia was present only in atenolol-treated SHRs. The heart weight:body weight ratio fell more in SHRs medicated with olmesartan versus those receiving atenolol. These changes were associated with increases in plasma Ang II in SHRs given the angiotensin II receptor blocker. At the end of treatment, plasma Ang (1-7) was higher in the olmesartan than atenolol or vehicle groups. The glomerular sclerosis (GS) index was lowered by olmesartan and atenolol compared with the vehicle group. While both olmesartan and atenolol attenuated renal perivascular collagen deposition (PVCD), the greatest effect was observed in SHRs receiving olmesartan. Elevations in plasma Ang (1-7) correlated negatively with reductions in GS or PVCD index, respectively. CONCLUSIONS: While control of blood pressure remains a critical factor in the prevention of hypertensive nephropathy, Ang (1-7) may play a substantial role in preventing the structural changes in glomerulus through its effect on regulations of blood pressure and renal function. PMID- 22089475 TI - Decorin in atherosclerosis. AB - Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality in the Western world. Despite tremendous strides in understandings its pathogenesis, it still remains a challenge because of gaps in our understanding of its initiation, progression and complications leading to the clinical syndromes of angina, acute coronary syndrome, cerebrovascular disease and peripheral vascular disease. Recent studies have provided impetus on the shift from models of atherosclerosis based on cellular interactions to models where the important role of extracellular matrix is recognized. Proteoglycans, especially those belonging to the small leucine-rich proteoglycan family of which decorin is a representative example, have come under close scrutiny for their role in atherogenesis. There is evidence from in vitro and in vivo animal models as well as humans to suggest an important role of decorin in attenuating progression of atherosclerosis. Decorin distribution in different blood vessels has been shown to inversely correlate with the tendency to develop atherosclerosis. Decorin seems to interact closely with different cellular components of the plaque milieu, thereby suggesting its role in influencing atherogenesis at different steps. Here we review the current understanding of the role of decorin in the pathogenesis of atherosclerosis. PMID- 22089476 TI - Inspiratory loading intensity does not influence lactate clearance during recovery. AB - PURPOSE: This study examined the effects of different pressure threshold inspiratory loads on lactate clearance and plasma acid-base balance during recovery from maximal exercise. METHODS: Eight moderately trained males (VO(2peak) = 4.29 +/- 0.46 L.min-1) performed, on different days, four maximal incremental cycling tests (power started at 0 W and increased by 20 W.min-1) of identical duration (exercise time during the first trial was 16.32 +/- 1.12 min). During 20-min recovery, subjects either rested passively or breathed through a constant pressure threshold inspiratory load of 10 (ITL10), 15 (ITL15), or 20 (ITL20) cm H2O. Plasma lactate concentration ([La-]) was measured, and acid-base balance was quantified using the physicochemical approach, which describes the dependency of [H+] on the three independent variables: strong ion difference ([Na+] + [K+] - [Cl-] + [La-]), the total concentration of weak acids, and the partial pressure of carbon dioxide. RESULTS: Peak exercise responses were not significantly different between trials. During recovery, the area under the plasma [La] curve was not different between trials (pooled mean = 261 +/- 60 mEq) and the [La] measured at the end of the 20-min recovery was also similar (passive recovery = 9.2 +/- 3.1 mEq.L-1, ITL10 = 9.3 +/- 3.1 mEq.L-1, ITL15 = 8.7 +/- 2.8 mEq.L-1, ITL20 = 8.7 +/- 3.2 mEq.L-1). Similarly, changes in other strong ions contributing to strong ion difference and total concentration of weak acids, partial pressure of carbon dioxide, and, therefore, [H+] were not different between trials. CONCLUSIONS: These data suggest that, in individuals of moderate endurance training status, inspiratory loading at the intensities used in the present study does not accelerate lactate clearance or modify plasma acid-base balance during recovery from maximal exercise. PMID- 22089477 TI - Is high-impact sports participation associated with bowlegs in adolescent boys? AB - PURPOSE: The purpose of this study was to investigate whether the participation in load bearing sports is associated with significant knee alignment adaptations in adolescent boys, which might cause a higher risk for the development of knee osteoarthritis in later life. METHODS: Five hundred twenty-one healthy boys (from 7 to 18 yr), selected from local primary and secondary schools, participated in the study. Two hundred sixty-five of them practiced competitive sports (track and field, field hockey, basketball, volleyball, tennis, badminton, and squash) for at least 3 h.wk(-1). The other remaining 256 boys did not practice any kind of sports. Genu varum/valgum was determined by measuring the intercondylar (IC) and intermalleolar (IM) distance with the subjects in a relaxed erect standing position. The IC and/or IM distance was measured using a caliper. Both measurements were combined to one parameter: the IC-IM distance. A one-way ANOVA was performed to analyze differences between the different age groups within the sporting and nonsporting boys separately. For each age group, the IC-IM distances of the sporting and nonsporting boys were compared by ANOVA with post hoc Bonferroni corrections. RESULTS: A comparison between the sporting and nonsporting boys showed that the sporting boys had a significantly higher degree of genu varum from 13 to 15 yr or older (P = 0.01). CONCLUSIONS: From the results of this study, it can be concluded that practicing load bearing sports in general is associated with the same knee varus alignment in adolescent boys as previously has been indicated in intense soccer-playing adolescents. PMID- 22089478 TI - Disparities in youth physical activity in the United States: 2003-2006. AB - PURPOSE: This study aimed to examine changes in physical activity among children and adolescents, by race/ethnicity, in the United States from 2003-2004 to 2005 2006. METHODS: Secondary analysis of the objectively measured accelerometer data among children and adolescents 6-19 yr: 2003-2004 (n = 1665) and 2005-2006 (n = 1716) from the nationally representative National Health and Nutrition Examination Survey 2003-2004 and 2005-2006. We estimated regression coefficients for change between the two periods by age group, accounting for sampling design and adjusting for age, sex, race/ethnicity, and number of hours monitored. We tested for differences in mean accelerometer counts per minute and minutes per day of moderate and vigorous physical activity trends by race/ethnicity and gender. RESULTS: Physical activity decreased with age, boys were more active than girls, and non-Hispanic black children were more active than non-Hispanic whites (all P < 0.01). Overall mean accelerometer counts increased from 2003-2004 to 2005-2006 for children ages 6-11 yr (+31.6 counts per minute; 95% confidence interval = 0.51-62.6) but not among adolescents ages 12-19 yr. There was an increase over time in mean accelerometer counts among 6- to 11-yr-old non Hispanic white children (+52.4 counts per minute, P = 0.007; 95% confidence interval = 15.7-89) but a decrease among non-Hispanic black and Mexican American children. No changes over the period in moderate and vigorous physical activity were found in either age group. CONCLUSIONS: The lack of improvement in physical activity among all children and adolescents and a potentially emerging race ethnic disparity indicate a need for further research on potential mechanisms underlying these differences. Effective interventions to improve physical activity opportunities and attenuate the decline in activity levels as children enter adolescence are needed. PMID- 22089479 TI - Effect of fatigue on landing biomechanics after anterior cruciate ligament reconstruction surgery. AB - PURPOSE: The purpose of this study was to determine the effects of fatigue on lower limb biomechanics during landing in patients who had undergone anterior cruciate ligament (ACL) reconstruction surgery. METHODS: Fifteen male participants who had undergone primary ACL reconstruction 15-19 months previously and 11 uninjured male control subjects had three-dimensional lower limb kinematics and kinetics quantified during single-limb landings, both before and during progression to fatigue. The single-limb landings were a vertical drop from a 30-cm platform, and subjects performed repetitive bilateral squats to induce fatigue. RESULTS: Fatigue led to reduced flexion in the lower limb, increased hip and knee abduction, increased knee rotation, and reduced knee joint moments. The response to fatigue was similar between the ACL-reconstructed limb and the control group as well as the reconstructed limb and the contralateral limb. The only kinematic variable to show a between-group or between-limb difference was hip flexion at initial contact, whereby flexion was greater for the reconstructed side. Although knee flexion and adduction moments were smaller for the reconstructed knee compared with the contralateral knee, they were not different from the control group. CONCLUSIONS: The results show that having an ACL reconstruction does not necessarily mean greater vulnerability to the effect of fatigue during single-limb landing. Nonetheless, some of the landing positions that were observed with fatigue potentially compromise the knee and integrity of the ACL graft. PMID- 22089480 TI - Are under- and overweight female elite athletes thin and fat? A controlled study. AB - PURPOSE: The study's purpose was to relate body mass index (BMI) to body fat percentage as measured by dual-energy x-ray absorptiometry in female elite athletes from different sports and nonathletic controls and to investigate what characterizes the athletes with unhealthy low and high body fat values. METHODS: This study was conducted in three phases: 1) screening with a detailed questionnaire, 2) body composition measurement (dual-energy x-ray absorptiometry), and 3) clinical interview. All female elite athletes representing national teams at the junior or senior level age 13-39 yr (n = 938) and an age group-matched randomly selected population-based control group (n = 900) were invited to participate. A stratified random sample was invited to participate in parts 2 and 3. A total of 186 athletes (62%) and 145 controls (48%) participated in all three phases. RESULTS: Of those athletes with normal BMI values (18.5-24.9 kg.m-2) (n = 150), 2.0% were classified with low body fat levels (<12%), and 6.7% were classified with obese body fat levels (>= 33%). The median value for the entire group was 24.3% body fat. For the controls with normal BMI values (n = 96), none was classified with low body fat levels, and 50% were classified with obese body fat levels (median = 33.1%). The correlation between BMI and body fat percentage was 0.671 (P < 0.01) (SEE = 5.3%) for the athletes and 0.813 (P < 0.01) (SEE = 4.1%) for the controls. Both under- and overfat athletes self-reported menstrual dysfunction, stress fractures, history of weight fluctuation, and use of pathogenic weight control methods and were diagnosed with clinical eating disorders and/or low bone density. CONCLUSIONS: Our data show that BMI is not a valid measure for assessing or monitoring body composition in female elite athletes, and it should be used carefully in female nonathletes. PMID- 22089481 TI - Ground contact time as an indicator of metabolic cost in elite distance runners. AB - Differences in running economy at common speeds have been demonstrated between male and female distance runners, as well as between middle-distance (MD) and long-distance (LD) specialists. Whether measures of foot ground contact time (tc), known to be proportional to the mass-specific cost of locomotion, follows the same running economy relationships in these groups is unknown. PURPOSE: This study examined if differences in tc and selected gait kinematic variables exist between elite male and female distance runners, as well as between elite MD and LD specialists, as running speed increases. METHODS: Twelve male and six female elite distance runners completed multiple 30-s trials on a treadmill at common competitive racing velocities. Wireless triaxial 10-g accelerometers, sampling at 1024 Hz, were securely attached to the laces of each shoe. Values of tc, swing time, stride length, and stride frequency were determined from accelerometric output corresponding to foot strike and toe-off events obtained from a minimum of 20 consecutive steps of each foot. A proportional estimate of metabolic cost was obtained by using 1/tc. RESULTS: Women displayed shorter tc, swing time, and stride length with greater stride frequency compared with men at common speeds; however, these differences were largely negated by normalizing to standing height. At common speeds, women demonstrated smaller measures of tc compared with men, suggesting an increased metabolic cost, paralleling published oxygen uptake data. MD specialists displayed smaller increases in 1/tc as speed increased, compared with LD specialists. CONCLUSIONS: Elite distance runners demonstrate ground contact measures that suggest that known differences in running economy between sexes and event specialties may be a result of differences in running gait. PMID- 22089482 TI - Repeated sprints alter signaling related to mitochondrial biogenesis in humans. AB - PURPOSE: We investigated the effects of acute and chronic repeated-sprint exercise (RSE) on the skeletal muscle messenger RNA (mRNA) expression and protein abundance/phosphorylation associated with mitochondrial biogenesis. METHODS: Ten healthy young adults (seven males, three females) performed the RSE trial, comprising three sets of 5 * 4-s maximal sprints on a nonmotorized treadmill, with a 20-s recovery between sprints and 4.5 min between sets. After 4 wk of repeated-sprint training, three times per week, participants repeated the RSE. A vastus lateralis muscle biopsy was obtained at rest, immediately after, and 1 and 4 h after RSE, before and after training. Venous blood lactate and glucose were measured at rest and during recovery. Real-time reverse transcriptase polymerase chain reaction and Western blot techniques were used to measure mRNA expression and protein abundance, respectively. RESULTS: Acute RSE increased the phosphorylation of acetyl-CoA carboxylase (86%, effect size (ES) = 1.4 +/- 0.8, P < 0.001) and Ca calmodulin-dependent protein kinase II (69%, ES = 0.7 +/- 0.6). Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha; 208%, ES = 1.5 +/- 0.7, P < 0.001) and nuclear respiratory factor 1 (92%, ES = 0.7 +/- 0.8) mRNA expression was increased after RSE. Four weeks of training increased the abundance of PGC-1alpha protein at rest (33%, ES = 0.9 +/- 0.7). CONCLUSIONS: Both acute and chronic RSE, despite only 60 s and 12 min of exercise, respectively, altered the molecular signaling associated with mitochondrial adaptations and PGC-1alpha mRNA expression in skeletal muscle. However, the small-to-moderate changes in resting PGC-1alpha protein abundance after training, together with the absence of changes in aerobic fitness, require further research to understand the functional significance of PGC-1alpha in response to RSE. PMID- 22089483 TI - Muscle coordination patterns for efficient cycling. AB - INTRODUCTION/PURPOSE: Cycling is a repetitive activity using coordinated muscle recruitment patterns to apply force to the pedals. With more muscles available for activation than required, some patterns produce high power, whereas some are more efficient. The purpose of this study was to identify relationships between muscle coordination and factors affecting muscle coordination to explain changes in overall mechanical efficiency (etaO). METHODS: Surface EMG, kinematics, and pedal forces were measured at 25%, 40%, 55%, 60%, 75%, and 90% VO(2max). Principal component analysis was used to establish muscle coordination, kinematic, and pedal force patterns associated with high and low etaO. RESULTS: At 55%-60% VO(2max), etaO was maximized and was highly related to the muscle coordination patterns. At high etaO, there was more medial and lateral gastrocnemii and soleus; less gluteus maximus, rectus femoris, and tibialis anterior; later medial and lateral vastii and biceps femoris; and earlier semitendinosus muscle activity resulting in an even distribution and synchronization of peak activity. Also, the ankle was more plantar flexed through the top and downstroke of the pedal cycle and more dorsiflexed during the upstroke for high etaO. The etaO was independent of the pedal force application. CONCLUSIONS: The results indicate that increased etaO is achieved through the coordination of muscles crossing the same joint, sequential peak activation from knee to hip to ankle, and reliance on multiple muscles for large joint torques. Also, muscle activity variability across the top and bottom of the cycle indicates that left and right leg muscle coordination may play a significant role in efficient cycling. These findings imply that cycling at 55%-60% VO(2max) will maximize the rider's exposure to high efficient muscle coordination and kinematics. PMID- 22089484 TI - Muscle coordination during an outdoor cycling time trial. AB - INTRODUCTION/PURPOSE: Muscle activity in cycling has primarily been studied in the laboratory; however, conclusions are limited by the ability to recreate realistic environmental conditions. The purpose of this study was to determine muscle coordination patterns in an outdoor time trial and investigate their relationships to power output (PO), total muscle activity (Itot), overall mechanical efficiency (etaO), cadence, and gradient. METHODS: Surface EMG, gradient, and cycling parameters were measured while cycling 18.8 km outdoors. A principal component analysis was used to establish coordination patterns that were compared with Itot, etaO, PO, cadence, and gradient. RESULTS: PO was positively correlated with Itot, and high PO was associated with elevated rectus femoris and vastus lateralis activity and synchronization of muscles crossing the same joint. PO and cadence demonstrated positive and negative relationships, respectively, with gradient. Relationships between muscle coordination, PO, etaO, Itot, and gradient showed that muscle coordination, PO, and etaO fluctuate during an outdoor time trial as a result of pacing and gradient. A trade-off existed between etaO and PO, and etaO was dependent on muscle activation around the top and bottom of the pedal cycle and activity in more than the knee extensor muscles. Fluctuations in muscle activity due to the changing PO, from pacing and terrain, seemed to mitigate fatigue indices seen in indoor cycling studies. CONCLUSIONS: This study provides evidence that muscle activity is dependent on the terrain aspects of the cycle course as muscle coordination changes with the altered locomotor demands. The coordination patterns significantly covaried with PO, Itot, etaO, cadence, and gradient, which highlights the importance of recording these parameters under field conditions and/or careful reproduction of outdoor environments in indoor studies. PMID- 22089485 TI - Course introduction and selection of immunohistochemical staining panels: principles and importance of incorporating clinical information. The 5th annual retreat for applied immunohistochemistry and molecular pathology january 30th february 2, 2011, coral gables, Florida. AB - Among the core principles in the practice of immunohistochemistry is the use of carefully chosen marker panels. Choosing an appropriate panel of antibodies is predicated on a sound differential diagnosis that is based on detailed examination of hematoxylin and eosin-stained slides. The panel should contain antibodies designed to be immunoreactive in the most likely disease(s) in the differential as well as selected negative markers. In addition, the importance of detailed historical and clinical information in constructing the differential diagnosis and panel selection cannot be understated. Two cases from the Case Presentation sessions of the 5th Annual Retreat for Applied Immunohistochemistry and Molecular Pathology are summarized to illustrate these points. The first case is that of metastatic well-differentiated neuroendocrine tumor (carcinoid) tumor presenting as a breast mass. The second is that of a squamous cell carcinoma of the lung mimicking a tumor with admixed glandular differentiation by entrapment and disruption of bronchial glands. Application of a select immunohistochemistry panel in light of the differential diagnosis and importance of making a specific diagnosis are discussed. PMID- 22089486 TI - From microscopy to whole slide digital images: a century and a half of image analysis. AB - In the year 1850, microscopes had evolved in quality to the point that the "first pathologists emerged from the treacherous swamps of medieval practice onto the relatively firm ground that histopathology seemed to offer." These early pathologists began to practice the art of image analysis, and diagnostic surgical pathology was born. Today the traditional microscope, in the hands of an experienced pathologist, is established as the gold standard for diagnosis of cancer and other diseases. Nonetheless, it is a tool and a technology that is more than 150 years old. Rapid advances in the capabilities of digital imaging hardware and software now offer the real possibility of moving to a new level of practice, using whole slide digital images for diagnosis, education, and research in morphologic pathology. Potential efficiencies in work flow and diagnostic integration, coupled with the use of powerful new analytic methods, promise radically to change the future shape of surgical pathology. PMID- 22089487 TI - Multiplexed measurement of proteins in tissue in a clinical environment. AB - There is an emerging need for more effective approaches to accurately quantitate protein expression in tissue samples. In many clinical studies and particularly in pharmaceutical clinical trials, access to adequate tissue samples is a major bottleneck, and thus techniques to measure protein expression in these valuable tissue specimens is important. This study will review current approaches in multiplexing of protein expression in tissue, and discusses new approaches using a novel image registration technique across multiple tissue sections. PMID- 22089488 TI - ASCO-CAP guidelines for breast predictive factor testing: an update. AB - This brief report compares and contrasts the American Society of Clinical Oncology/College of American Pathologists guidelines for breast cancer predictive factor testing including the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor, type 2, erbB2 Guideline published in 2007 and the recently published Guideline for Estrogen Receptor and Progesterone Receptor Testing by Immunohistochemistry, published in 2011. PMID- 22089489 TI - Immunohistochemistry in the diagnostic evaluation of breast lesions. AB - Most diagnoses in breast pathology can be rendered after careful evaluation of a high quality hematoxylin and eosin-stained tissue section. However, a significant number of both benign and malignant lesions can show variable morphologic patterns and significant histologic overlap, leading to diagnostic uncertainty. These challenges and complexities have opened the door to an expanding role for immunohistochemistry (IHC) as an important diagnostic adjunct for solving frequently encountered problems in breast pathology. Although IHC has proven to be a powerful tool in helping to resolve difficult cases, the results of such studies should always be carefully interpreted within the morphologic context for each lesion. This article will briefly review some of the more common circumstances in which IHC has been shown to be useful in diagnostic breast pathology. PMID- 22089490 TI - HER2 testing in gastric and gastroesophageal junction cancers: a new therapeutic target and diagnostic challenge. AB - Adenocarcinomas of the stomach and gastroesophageal junction represent a major cause of cancer morbidity and mortality world wide. Complete surgical resection is the mainstay of treatment for nonmetastatic disease; however, many patients are not diagnosed until their disease is either locally advanced or metastatic and therefore unresectable. Clearly, there is an unmet clinical need for new therapeutic strategies, treatment options, and novel therapeutic targets. In a recent trial (Trastuzumab for GAstric cancer), patients assigned to the trastuzumab treatment protocol showed an improved overall survival over those not receiving treatment. Trastuzumab has recently been approved for treatment of advanced gastric and gastroesophageal junction cancers. Pathologists and diagnostic laboratories must be prepared for this new category of specimens requiring human epidermal growth factor receptor 2 testing, and have an awareness of the interpretive differences between breast and gastric cancers. PMID- 22089491 TI - Electron theory of fast and ultrafast dissipative magnetization dynamics. AB - For metallic magnets we review the experimental and electron-theoretical investigations of fast magnetization dynamics (on a timescale of ns to 100 ps) and of laser-pulse-induced ultrafast dynamics (few hundred fs). It is argued that for both situations the dominant contributions to the dissipative part of the dynamics arise from the excitation of electron-hole pairs and from the subsequent relaxation of these pairs by spin-dependent scattering processes, which transfer angular momentum to the lattice. By effective field theories (generalized breathing and bubbling Fermi-surface models) it is shown that the Gilbert equation of motion, which is often used to describe the fast dissipative magnetization dynamics, must be extended in several aspects. The basic assumptions of the Elliott-Yafet theory, which is often used to describe the ultrafast spin relaxation after laser-pulse irradiation, are discussed very critically. However, it is shown that for Ni this theory probably yields a value for the spin-relaxation time T(1) in good agreement with the experimental value. A relation between the quantity alpha characterizing the damping of the fast dynamics in simple situations and the time T(1) is derived. PMID- 22089492 TI - Suppression of collagen-induced arthritis by intra-articular lentiviral vector mediated delivery of Toll-like receptor 7 short hairpin RNA gene. AB - Knockdown of Toll-like receptors (TLRs) is a novel therapeutic strategy in treating patients with rheumatoid arthritis (RA). We examined the effects of lentiviral vector-mediated delivery of TLR7 short hairpin RNA gene (Lt.shTLR7) on collagen-induced arthritis (CIA). After being immunized on days 0 and 7, Sprague Dawley rats received intra-articular (i.a.) injection of Lt.shTLR7 or scramble control vector on days 7 and 10. The therapeutic effects were evaluated by measuring ankle circumferences, articular index, and radiographic and histological scores on killing on day 16. Microvessel densities, vascular endothelial growth factor (VEGF) levels, pro-inflammatory cytokine concentrations and T-cell numbers within the synovial tissues were measured. Moreover, VEGF and pro-inflammatory cytokine concentrations in culture supernatants from TLR7 transfected synovial fibroblasts (SFs) stimulated with imiquimod or endogenous ligands were examined. There were significant reduction in ankle circumferences, articular indexes, and radiographic and histological scores. Microvessel densities, VEGF concentrations, interleukin (IL)-1beta and IL-6 levels and T-cell densities within synovial tissues were significantly lower. Induction of VEGF, IL 1beta and IL-6 production from stimulated SFs was significantly suppressed. Taken together, these data demonstrate the effects of i.a. lentiviral vector-mediated delivery of shTLR7 RNA gene on inhibition of CIA, and implicate the manipulation of TLR7 as a potential therapeutic strategy in RA patients. PMID- 22089493 TI - Gene-based therapies for dominantly inherited retinopathies. AB - In light of the elucidation of the molecular pathogenesis of some dominantly inherited retinal degenerations over the past two decades, it is timely to explore possible means of therapeutic intervention for such diseases. However, the presence of significant levels of intergenic and intragenic genetic heterogeneity in this group of dominant conditions represents a barrier to the development of therapies focused on correcting the primary genetic defect. More than 60 genes have been implicated in dominant retinopathies and indeed over 150 different mutations in the rhodopsin gene alone have been identified in patients with autosomal dominant retinitis pigmentosa. Employing next-generation sequencing to characterise populations of retinal degeneration patients genetically over the coming years will beyond doubt serve to highlight further the immense genetic heterogeneity inherent in this group of disorders. Such diversity in genetic aetiologies has promoted the search for therapeutic solutions for dominantly inherited retinopathies that are independent of disease causing mutations. The various approaches being considered to provide mutation independent therapies for these dominant conditions will be discussed in the review, as will the preclinical data supporting the further development of such strategies. PMID- 22089495 TI - dsAAV8-mediated gene transfer and beta-cell expression of IL-4 and beta-cell growth factors are capable of reversing early-onset diabetes in NOD mice. AB - Type-I diabetes is a chronic disease mediated by autoimmune destruction of insulin-producing beta-cells. Although progress has been made towards improving diabetes-associated pathologies and the quality of life for those living with diabetes, no therapy has been effective at eliminating disease manifestations or reversing disease progression. Here, we examined whether double-stranded adeno associated virus serotype 8 (dsAAV8)-mediated gene delivery to endogenous beta cells of interleukin (IL)-4 in combination with beta-cell growth factors can reverse early-onset diabetes in NOD mice. Our results demonstrate that a single treatment with dsAAV8 vectors expressing IL-4 in combination with glucagon-like peptide-1 or hepatocyte growth factor/NK1 under the regulation of the insulin promoter enhanced beta-cell proliferation and survival in vivo, significantly delaying diabetes progression in NOD mice, and reversing disease in ~10% of treated NOD mice. These results demonstrate the ability to reverse hyperglycemia in NOD mice with established diabetes by in vivo gene transfer to beta-cells of immunomodulatory factors and beta-cell growth factors. PMID- 22089494 TI - Prolonged regulatable expression of EPO from an HSV vector using the LAP2 promoter element. AB - We previously reported regulated expression of erythropoietin (EPO) over 4 weeks in the peripheral nerve in vivo, using a herpes simplex virus (HSV)-based vector containing a Tet-on regulatable gene expression cassette. To create a vector that would be appropriate for the treatment of chronic neuropathy, we constructed a HSV vector with expression of EPO under the control of the Tet-on system in which the HSV latency-associated promoter 2 element was used to drive the expression of the Tet-on transactivator. EPO expression from the vector was tightly controlled by administration of doxycycline (DOX) in vitro. One month after inoculation of the vector to transduce dorsal root ganglion (DRG) in vivo, administration of DOX containing chow-induced expression of EPO. Mice with streptozotocin-induced diabetes, inoculated with the vector, were protected against the development of neuropathy by continuous administration of DOX-containing chow over the course of 3 months. Identical results were achieved when DOX was administered every other week over 3 months of diabetes, but administration of DOX, 1 week out of 3, provided only partial protection against the development of neuropathy. Taken together, these results suggest such a vector is well suited for clinical trial for the treatment of chronic or subacutely developing neuropathy. PMID- 22089496 TI - Shutdown of immunological priming and presentation after in vivo administration of adenovirus. AB - Adenoviral (Adv) vectors are widely used in both experimental and clinical trials for vaccination and gene therapy. Recombinant Adv can evoke potent innate immune responses and adaptive immune responses to encoded antigens. However, how Adv infection affects the response to subsequently encountered antigens is poorly understood. We show that intravenously administered replication defective (E1 and E3 deleted) Adv educes functional changes in dendritic cells (DC) resulting in impaired priming of cytotoxic T lymphocytes (CTL) more than 7 days after Adv treatment. Generalized DC activation was indicated by transient upregulation of CD86 and reduced endocytosis of fluorescent beads. It is known that CD8+ DC are predominantly responsible for uptake and presentation (cross-presentation) of exogenous antigens to CD8+ CTL. Hence, impaired endocytosis in CD8+, but not CD8 , DC at 7 days after Adv administration provided an explanation for the impaired CTL response to antigen at this time. Shutdown of cross-presentation was confirmed using cytochrome c (cytc), an agent that selectively depletes cross presenting DC. Adv-infection rendered CD8+ DC resistant to depletion by cytc. As the cross-presentation pathway underlies CD8 T-cell responses to many cancers and to vaccines or viruses that do not directly infect DC, systemic Adv administration may impair these responses. PMID- 22089497 TI - Stochastic rolling of a rigid sphere in weak adhesive contact with a soft substrate. AB - We study the rolling motion of a small solid sphere on a fibrillated rubber substrate in an external field in the presence of a Gaussian noise. From the nature of the drift and the evolution of the displacement fluctuation of the ball, it is evident that the rolling is controlled by a complex non-linear friction at a low velocity and a low noise strength (K), but by a linear kinematic friction at a high velocity and a high noise strength. This transition from a non-linear to a linear friction control of motion can be discerned from another experiment in which the ball is subjected to a periodic asymmetric vibration in conjunction with a random noise. Here, as opposed to that of a fixed external force, the rolling velocity decreases with the strength of the noise suggesting a progressive fluidization of the interface. A state (K) and rate (V) dependent friction model is able to explain both the evolution of the displacement fluctuation as well as the sigmoidal variation of the drift velocity with K. This research sets the stage for studying friction in a new way, in which it is submitted to a noise and then its dynamic response is studied using the tools of statistical mechanics. Although more works would be needed for a fuller realization of the above-stated goal, this approach has the potential to complement direct measurements of friction over several decades of velocities and other state variables. It is striking that the non-Gaussian displacement statistics as observed with the stochastic rolling is similar to that of a colloidal particle undergoing Brownian motion in contact with a soft microtubule. PMID- 22089498 TI - Uncommon presentations of uncommon conditions. PMID- 22089499 TI - Role of the macular optical coherence tomography scan in neuro-ophthalmology. AB - BACKGROUND: Recent improvements in optical coherence tomographic (OCT) resolution and automated segmentation software have provided a means of relating visual pathway damage to structural changes in the retinal nerve fiber layer (RNFL) and corresponding soma of the ganglion cells in the inner layers of the macula and also in the outer photoreceptor layer in the macula. EVIDENCE ACQUISITION: Studies correlating retinal structure with function are reviewed in the context of OCT in optic nerve and retinal disorders. RESULTS: Recently published work provides evidence showing a strong relationship not only between the RNFL and visual threshold in optic nerve disorders but also between visual sensitivity and the inner layers of the retina in the macula, where the cell bodies of ganglion cells reside. Acquired and genetic disorders affecting the outer retina show correlation between visual sensitivity and the thickness of the outer photoreceptors. These relationships help localize unknown causes of visual field loss through segmentation of the retinal layers using spectral domain OCT. CONCLUSIONS: Advances in relating the structure of the ganglion cell layer in the macula to the corresponding axons in the RNFL and to visual function further our ability to differentiate and localize ambiguous causes of vision loss and visual field defects in neuro-ophthalmology. Ganglion cell layer analysis in volume OCT data may provide yet another piece of the puzzle to understanding structure function relationships and its application to diagnosis and monitoring of optic nerve diseases, while similar structure-function relationships are also being elucidated in the outer retina for photoreceptor diseases. PMID- 22089501 TI - Stenting of the transverse sinuses in idiopathic intracranial hypertension. PMID- 22089502 TI - Neuro-ophthalmology and pregnancy: what does a neuro-ophthalmologist need to know? AB - Management of the pregnant woman with a neuro-ophthalmic disorder may be challenging. Physiologic changes in pregnancy make vascular conditions more frequent, including retinal artery occlusion, spontaneous orbital hemorrhage, and pituitary apoplexy. Papilledema may signal cerebral venous sinus thrombosis or idiopathic intracranial hypertension. Manifestations of severe preeclampsia and eclampsia include choroidal infarction, serous retinal detachment, and disorders of higher cortical function, such as alexia, simultanagnosia, and cerebral blindness. Cranial neuropathies have also been reported. Transient Horner syndrome, intracranial hypotension with comitant esotropia may occur in the postpartum period. Treatment of the neuro-ophthalmic complications of pregnancy requires an understanding of the risks of medications. Taking optimal care of the mother will usually result in the best care for her baby. PMID- 22089500 TI - Vision in multiple sclerosis: the story, structure-function correlations, and models for neuroprotection. AB - Visual dysfunction is one of the most common clinical manifestations of multiple sclerosis (MS). Just over a decade ago, MS clinical trials did not include visual outcomes, but experts recognized the need for more sensitive measures of visual function. Low-contrast letter acuity emerged as the leading candidate to measure visual disability in MS, and subsequent studies found low-contrast acuity testing to correlate well with brain MRI lesion burden, visual-evoked potentials, quality of life (QOL), and retinal nerve fiber layer (RNFL) loss, as measured by optical coherence tomography (OCT). OCT in MS has allowed for assessment of structure function correlations that make the anterior visual pathway and acute optic neuritis (ON) ideal models for testing novel agents for neuroprotection and repair. New therapies that reduce axonal loss by neuroprotective or myelin repair mechanisms can now be assessed noninvasively by OCT and coupled with visual function data. Based on OCT studies in MS, RNFL thickness is reduced significantly among patients (92 MUm) vs controls (105 MUm) and is particularly reduced in MS eyes with a history of ON (85 MUm). Worsening of visual function by a clinically significant >= 7 letters or approximately 1.5 lines for low-contrast acuity is associated with approximately 4.5 MUm reductions in RNFL thickness in MS eyes. Longitudinal studies of OCT have also shown RNFL axonal loss over time that occurs even in the absence of acute ON and that correlates with clinically meaningful worsening of vision and QOL, even in patients with benign MS. The latest OCT investigations involve high-resolution spectral-domain (SD) OCT with segmentation and measurement of specific retinal layers using computerized algorithms. These methods allow quantitation of ganglion cell (neuronal) layer loss and axonal degeneration in MS in vivo. In this review, we examine the data from these studies and ongoing trials that highlight the entity of ON as a model to investigate neuroprotection and neurorepair. In doing so, we also present representative group data from studies that have examined visual function, OCT measures, and QOL scales in patients with MS and ON and disease-free controls. These data, and those from recent meta-analyses, may be used to provide reference values for the development of clinical trial protocols. PMID- 22089504 TI - Psoriasis and the pregnant woman: what are the key considerations? AB - Pregnancy is characterized by multiple physiologic changes. During the entire gestational period, both mother and infant are vulnerable to a variety of external and internal factors. Maternal disease, use of certain medications, drugs, alcohol, smoking, and radiation exposure can have devastating effects on the fetus. Pregnancy-related complications in women with psoriasis can be caused by both the disease and the treatment. The response of the maternal placenta to psoriasis-induced inflammation and comorbid conditions, such as obesity, hypertension, and depression, may also influence the pregnancy. Herein, we review the relationship between psoriasis and undesirable pregnancy outcomes. PMID- 22089505 TI - Newer approaches in topical combination therapy for acne. AB - Acne vulgaris is a common chronic inflammatory cutaneous disease involving the pilosebaceous unit. Its pathophysiology is multifactorial and complex, including obstruction of the pilosebaceous unit due to increased sebum production, abnormal keratinization, proliferation of Propionibacterium acnes (P. acnes), and inflammation. Topical agents are the most commonly used therapy for acne. First generation topicals mainly consist of single agent retinoids, benzoyl peroxide (BPO) and antibacterials that target comedones, P. acnes, and inflammation. Novel topical therapies include combination products with advanced vehicle formulations that target multiple acne pathophysiologies and offer simplified treatment regimes. For example, the combination of clindamycin and tretinoin in a unique vehicle formulation allows for progressive follicle penetration and decreased irritation, resulting in increased efficacy. Furthermore, adapalene or clindamycin with BPO combinations target comedones, inflammation, and P. acnes synergistically. These newer combination products have the potential to increase both efficacy and patient adherence when compared with single agent treatment. PMID- 22089506 TI - Specific recognition between intrinsically disordered LEF and DNA. AB - Lymphoid enhancer-binding factor-1 (LEF-1) is a sequence-specific and cell type specific transcription factor in regulation of the human T cell receptor alpha enhancer. It has been shown the minor groove of DNA can bind the intrinsic disordered LEF. To get an insight into the mechanism of how the intrinsic disordered LEF specifically recognizes DNA, we have performed explicit-solvent multiple molecular dynamics (MD) simulations to study the specific recognition between DNA and LEF. Room-temperature MD simulations suggest that the disordered C-tails of LEF have nonspecific and specific interactions with the minor groove of DNA. Kinetic analysis of high-temperature MD simulations shows that bound and apo-states unfold via a two-state process. The specific binding of the disordered C-tails of LEF can accelerate the formation of a complex. Gly38Ala and Met11Gly mutant simulations show that electrostatic interactions between DNA and LEF significantly decrease. Kolmogorov-Smirnov (KS) P test analysis illustrates that the specific recognition between DNA and LEF might follow an induced-fit mechanism. Furthermore, these methods can be used for the research of specific recognition between DNA and other intrinsic disordered proteins. PMID- 22089507 TI - A comparison between robust z and 0.3-Logit Difference procedures in assessing stability of linking items for the Rasch model. AB - There are at least two procedures to assess item difficulty stability in the Rasch model: robust z procedure and ".3 Logit Difference" procedure. The robust z procedure is a variation of the z statistic that reduces dependency on outliers. The ".3 Logit Difference" procedure is based on experiences in Rasch linking for tests developed by Harcourt. Both methods were applied to archival data from two large-scale South Carolina assessment programs: HSEE 1986/1987 and PACT 2004/2005.The results of the analysis showed the ".3 Logit Difference" procedure identifies slightly more stable items (2.6%) for all items under study. In addition, approximately 93% of all items under consideration were identically classified as stable or unstable for both procedures. This very high level of agreement between the two methods indicates that either procedure can be safely used to identify stable items for use in a common-item linking design. The advantage of the robust z procedure lies in its foundation of robust statistical inference. The procedure takes into account well-accepted models for identifying outliers and permits critical values set at a specified Type I error. PMID- 22089508 TI - Assessment of English language development: a validity study of a district initiative. AB - The San Francisco Unified School District (SFUSD) uses the Language and Literacy Assessment Rubric (LALAR) as the secondary measurement required by the No Child Left Behind (NCLB) Act to measure English proficiency of English language learners (ELLs). In this analysis, the Rasch model is used to identify whether the LALAR is a valid measurement instrument and scale to measure the "English proficiency" of ELLs. This analysis investigates the relationship between student ability () and the probability that the student will respond correctly to an item on the LALAR. Controlling for this relationship, the item characteristics of each item, ability of each student, and measurement error associated with each score were mathematically derived. This will allow for validity and reliability tests to be conducted, which will help determine if the LALAR is a useful accountability measure for ELLs. PMID- 22089509 TI - Equating of multi-facet tests across administrations. AB - The purpose of this study is to explore criteria for common element test equating for performance examinations. Using the multi-facet Rasch model, each element of each facet is calibrated or placed in a relative position on a Benchmark or reference scale. Common elements from each facet, included on the examinations being equated, are used to anchor the facet elements to the Benchmark Scale. This places all examinations on the same scale so that the same criterion standard can be used. Performance examinations typically have three to four facets including examinees, raters, items and tasks. Raters rate examinees on tasks related to the items included in the test. The initial anchoring of a current test administration to the Benchmark Scale is evaluated for invariance and fit. If there is too much variance or lack of fit for particular facet elements, it may be necessary to unanchor those elements, which means they are not used in the equating. The equating process was applied to an exam with four facets and another with five facets. Results found few common facet elements that could not be used in the test equating process and that differences in the difficulty of the equated exams were identified so that the criterion standard on the Benchmark Scale could be used. It was necessary to use careful quality control for anchoring the common elements in each facet. The common elements should be unaltered from their original use. Strict criteria for displacement and fit must be established and used consistently. Unanchoring inconsistent and/or misfitting facet elements improves the quality of the test equating. PMID- 22089510 TI - Examining student rating of teaching effectiveness using FACETS. AB - Students' evaluations of teaching staff can be considered high-stakes, as they are often used to determine promotion, reappointment, and merit pay to academics. Using Facets, the reliability and validity of one student rating questionnaire is analyzed. A total of 13,940 respondents of the Human Science Division of International Islamic University Malaysia were involved in the study. The analysis shows that the student rating questionnaire used was valid and reliable, and it allows identification of staff for the institution's prestigious teaching excellence awards, and those needing in-service training. It was found that there was no significant difference in terms of rank, age and gender of the staff. The study also shows that the majority of staff have problems keeping the class interested and getting students to participate in class activities. Faculty also hardly discussed common errors in assignments and tests. PMID- 22089511 TI - Exploring differential item functioning (DIF) with the Rasch model: a comparison of gender differences on eighth grade science items in the United States and Spain. AB - Traditionally, women and minorities have not been fully represented in science and engineering. Numerous studies have attributed these differences to gaps in science achievement as measured by various standardized tests. Rather than describe mean group differences in science achievement across multiple cultures, this study focused on an in-depth item-level analysis across two countries: Spain and the United States. This study investigated eighth-grade gender differences on science items across the two countries. A secondary purpose of the study was to explore the nature of gender differences using the many-faceted Rasch Model as a way to estimate gender DIF. A secondary analysis of data from the Third International Mathematics and Science Study (TIMSS) was used to address three questions: 1) Does gender DIF in science achievement exist? 2) Is there a relationship between gender DIF and characteristics of the science items? 3) Do the relationships between item characteristics and gender DIF in science items replicate across countries. Participants included 7,087 eight grade students from the United States and 3,855 students from Spain who participated in TIMSS. The Facets program (Linacre and Wright, 1992) was used to estimate gender DIF. The results of the analysis indicate that the content of the item seemed to be related to gender DIF. The analysis also suggests that there is a relationship between gender DIF and item format. No pattern of gender DIF related to cognitive demand was found. The general pattern of gender DIF was similar across the two countries used in the analysis. The strength of item-level analysis as opposed to group mean difference analysis is that gender differences can be detected at the item level, even when no mean differences can be detected at the group level. PMID- 22089512 TI - A Mapmark method of standard setting as implemented for the National Assessment Governing Board. AB - This article describes a Mapmark standard setting procedure, developed under contract with the National Assessment Governing Board (NAGB). The procedure enhances the bookmark method with spatially representative item maps, holistic feedback, and an emphasis on independent judgment. A rationale for these enhancements, and the bookmark method, is presented, followed by a detailed description of the materials and procedures used in a meeting to set standards for the 2005 National Assessment of Educational Progress (NAEP) in Grade 12 mathematics. The use of difficulty-ordered content domains to provide holistic feedback is a particularly novel feature of the method. Process evaluation results comparing Mapmark to Anghoff-based methods previously used for NAEP standard setting are also presented. PMID- 22089513 TI - Tunable, light-assisted co-generation of CO and H2 from CO2 and H2O by Re(bipy tbu)(CO)3Cl and p-Si in non-aqueous medium. AB - The light-assisted co-generation of carbon monoxide and hydrogen from carbon dioxide and water is reported. The combination of a homogeneous CO-evolving electrocatalyst and a heterogeneous H(2)-evolving photoelectrode surface provides for tunability of the H(2)/CO ratio. A total Faradaic efficiency of 102 +/- 5% and a H(2)/CO ratio of 2:1 were achieved at a low homogeneous catalyst concentration (0.5 mM) in acetonitrile/water mixtures. PMID- 22089514 TI - Fall incidence and risk factors in patients after total knee arthroplasty. AB - PURPOSE: To prospectively investigate the relationship between physical function and falls among elderly patients who underwent total knee arthroplasty (TKA) and to determine the incidence of falls as well as their risk factors. METHODS: A total of 108 patients (17 male, 91 female) over 60 years of age who underwent TKA were enrolled and who were living independently in community. 75 patients fulfilled our inclusion criteria and 74 (8 male, 66 female) of them agreed to participate. Baseline assessment (physical examination, physical performance tests, and self-administered questionnaire) were conducted between 6 and 12 months after the last arthroplasty and the follow-up assessment was performed 6 months after the baseline assessment. Monthly pre-stamped postcards were sent to assess the incidence of falls. RESULTS: Of the 74 patients enrolled, 70 (94.6%) completed a 6-month prospective observation. 23 of 70 patients (32.9%) fell during the observational period. Postoperative range of knee flexion, ranges of knee flexion and extension and ankle plantar flexion were significantly lower in fallers than in non-fallers (P = 0.016, P = 0.037, P = 0.014, respectively). In the multivariate analysis, postoperative range of knee flexion (OR 0.277, 95%CI 0.088-0.869, P = 0.028) and ankle plantar flexion (OR 0.594, 95%CI 0.374-0.945, P = 0.028) were determined to be significant risk factors. CONCLUSION: Elderly people who underwent TKA are considered more likely to fall compared with healthy elderly people. For patients with limited knee flexion and ankle plantar flexion, improvement of ROM by exercise therapy and patient education regarding the prevention of falls and fractures are considered necessary. PMID- 22089515 TI - Procedural sedation and analgesia and the propofol affair: a unique opportunity for anaesthesiology. PMID- 22089516 TI - 3,4-Methylenedioxymethamphetamine (Ecstasy) increases the sensitivity of the contractile apparatus to calcium ions in both malignant hyperthermia-susceptible and normal skeletal muscle fibres. AB - CONTEXT AND OBJECTIVES: The present study was designed to investigate whether 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') increases the sensitivity of the contractile apparatus to calcium in muscle fibres from malignant hyperthermia susceptible and malignant hyperthermia-negative pigs, whether it causes calcium ion release from the sarcoplasmic reticulum and whether it inhibits calcium reuptake into the sarcoplasmic reticulum. DESIGN: Experimental study, using a model of porcine saponin-skinned fibres. RESULTS: Administration of MDMA in concentrations of 1, 2 and 4 mmol l(-1)l did not result in relevant force transients in skinned muscle fibres of malignant hyperthermia-susceptible or malignant hyperthermia-negative pigs. Furthermore, MDMA in these concentrations did not alter calcium ion loading of the sarcoplasmic reticulum in either group. With regard to changes in the calcium ion sensitivity of the contractile proteins, however, MDMA dose-dependently increased (pCa50) values (negative decadic logarithm of [Ca2+] at which isometric force is half-maximal) in both groups. CONCLUSION: In the present study, we were able to demonstrate that MDMA dose-dependently increases the sensitivity of the contractile apparatus to calcium in both malignant hyperthermia-susceptible and malignant hyperthermia negative fibres. Consequently, the malignant hyperthermia status should not affect the calcium sensitivity of the contractile apparatus. However, the increased calcium sensitivity is an important finding that must be appreciated, particularly in relation to the agonistic effect of MDMA at the nicotinic acetylcholine receptor, which increases intracellular calcium ion concentrations. PMID- 22089517 TI - Quantifying prognosis with risk predictions. AB - Prognosis is a forecast, based on present observations in a patient, of their probable outcome from disease, surgery and so on. Research methods for the development of risk probabilities may not be familiar to some anaesthesiologists. We briefly describe methods for identifying risk factors and risk scores. A probability prediction rule assigns a risk probability to a patient for the occurrence of a specific event. Probability reflects the continuum between absolute certainty (Pi = 1) and certified impossibility (Pi = 0). Biomarkers and clinical covariates that modify risk are known as risk factors. The Pi as modified by risk factors can be estimated by identifying the risk factors and their weighting; these are usually obtained by stepwise logistic regression. The accuracy of probabilistic predictors can be separated into the concepts of 'overall performance', 'discrimination' and 'calibration'. Overall performance is the mathematical distance between predictions and outcomes. Discrimination is the ability of the predictor to rank order observations with different outcomes. Calibration is the correctness of prediction probabilities on an absolute scale. Statistical methods include the Brier score, coefficient of determination (Nagelkerke R2), C-statistic and regression calibration. External validation is the comparison of the actual outcomes to the predicted outcomes in a new and independent patient sample. External validation uses the statistical methods of overall performance, discrimination and calibration and is uniformly recommended before acceptance of the prediction model. Evidence from randomised controlled clinical trials should be obtained to show the effectiveness of risk scores for altering patient management and patient outcomes. PMID- 22089519 TI - Don't shoot the messnger: memory for misspellings in context. AB - Misspellings in sentences are usually easy to understand by readers due to top down influences. Although top-down processing allows for fluent reading of misspelled items, the nature of their representations in memory is not known. If representations of misspellings are distinct from representations of correctly spelled words, their influence should be seen in later recognition decisions. In this set of experiments, participants read words and misspellings embedded in sentences and were later given a recognition test. The sentences contained semantically biased or neutral contexts. In Experiment 1, misspellings were created by removing a single letter (e.g., drveway). In Experiment 2, the recognition items probes were presented in uppercase letters (e.g., DRVEWAY) to reduce the visual similarity between study and test items. In Experiment 3, the misspellings were created by substituting visually similar letters (e.g., driweway). In contrast to the previous experiments, in Experiment 4, participants were explicitly told about the memory test to see how response strategies affect performance. Overall, the results indicate that people retain surface feature information about misspellings which seem to inform their memory judgments, and that the processing of this information cannot be strategically controlled. PMID- 22089520 TI - Evidence for a non-lexical influence on children's auditory repetition of familiar words. AB - This paper examines evidence for a nonlexical influence on children's repetition of real words. We investigate the extent to which two computational models of auditory repetition can simulate the performance of 68 children aged between 5 and 11 years-old when they are attempting to repeat familiar words. Both computational accounts were derived from Foygel and Dell's (J Mem Lang 43:182 216, 2000) semantic-phonological model of picture-naming. Results showed that a dual-route model in which a lexical and a nonlexical route work together to repeat familiar words (Hanley et al. in Cogn Neuropsychol 21:147-158, 2004) provided an accurate simulation of children's repetition, whereas Foygel and Dell (J Mem Lang 43:182-216, 2000) single lexical-route model under-predicted performance. The only exception was the repetition performance of 5 year-old children, which was over-predicted by the dual-route model. It is argued that at 5 years of age, some children have available both a lexical and a nonlexical repetition route but the output of the two routes does not summate when real words are being repeated. Some young children may lack the attentional skills that would enable them to co-ordinate the activity of the lexical and nonlexical repetition routes. PMID- 22089521 TI - Perceptual processing of Mandarin nasals by L1 and L2 Mandarin speakers. AB - Nasals are cross-linguistically susceptible to change, especially in the syllable final position. Acoustic reports on Mandarin nasal production have recently shown that the syllable-final distinction is frequently dropped. Few studies, however, have addressed the issue of perceptual processing in Mandarin nasals for L1 and L2 speakers of Mandarin Chinese. The current paper addressed to what extent and in what directions L1 and L2 speakers of Mandarin differed in perceiving Mandarin nasals. Possible variables, including the linguistic backgrounds (i.e. L1 vs. L2 speakers of Mandarin Chinese), the vocalic contexts (i.e. [i, e, a, y, ua, ue, ia]) and the phonetic settings (i.e. syllable-initial vs. syllable-final), were discussed. Asymmetrical findings in the current investigation indicated limitations of speech learning theories developed from European languages in the context of Mandarin nasals. A tri-dimensional model was thus suggested for interpreting the cognitive mechanism in Mandarin nasal perception. PMID- 22089522 TI - Effects of orthography on speech production in Chinese. AB - The potential role of orthographic representations on spoken word production was investigated with speakers of Chinese, a non-alphabetic and orthographically non transparent language. Using the response generation procedure, we obtained the well-known facilitation from word-initial phonological overlap, but this effect was unaffected by whether or not responses shared the initial character. In a study which manipulated the visual similarity of the word-initial character, a significant inhibitory effect of orthography was found. However, this effect disappeared when prompt stimuli were presented auditorily, suggesting that the orthographic effect might be attributable to the memorization stage of the response generation task, rather than reflecting processes genuine to speaking. By contrast, a reliable orthographic effect was found in an oral reading task, suggesting that orthography plays a role only when it is relevant to the word production task. Furthermore, the present findings show that the orthographic effect is tied to the correspondence between orthography and phonology of a language when orthography is relevant to the task used. PMID- 22089523 TI - Intrathecal drug delivery system (IDDS) for cancer pain management: a review and updates. AB - Cancer pain remains undertreated and a significant number of patients with cancer pain die from severe untreated pain. With increasing survival rate in cancer, the prevalence of cancer pain is also increasing in number. Though majority of patients with cancer pain can be effectively treated with conventional medical management, still a significant portion of patients required some form of interventional pain management techniques. Among the interventional techniques, intrathecal drug delivery is increasingly used in cancer pain management. Our objective of this article is to review literatures and clinical studies on intrathecal drug delivery system (IDDS) in cancer pain management and to provide updates on its use, precautions, contraindications, side effects and its management, socioeconomic consideration, and management of IDDS in difficult or uncommon situations. PMID- 22089524 TI - Polyvalent DNA-graphene nanosheets "click" conjugates. AB - Graphene is an increasingly important nanomaterial exhibiting great promise in the area of nanotechnology. In this study, the azide-functionalized graphene derivative was synthesized as the 'click' reagent for preparation of polyvalent DNA-graphene conjugates, which provide an effective and stable platform to construct new functional nano-architectures. Assembled with Au nanoparticles, the prepared Au-DNA-graphene nanocomplex exhibits excellent stability that could prevent the nanocomplex from being destroyed by surfactants. Assembled with DNA tetrahedron-structured probes (TSPs), the nanocomplex displays outstanding sensitive electrochemiluminescence properties, which might be used as a biosensor for DNA detection. Therefore, this DNA-graphene conjugates could be explored as the assembly unit for advanced DNA nano-architectures in the field of DNA nanotechnology. PMID- 22089525 TI - Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic model. AB - Human bioaccumulative potential is an important element in the risk assessment of chemicals. Due to the high number of synthetic chemicals, there exists the need to develop prioritisation strategies. The purpose of this study was to develop a predictive tool for human bioaccumulation risk assessment that incorporates not only the chemical properties of the compounds, but also the processes that tend to decrease the concentration of the compound such as metabolisation. We used a generic physiologically based toxicokinetic model that based on in vitro human liver metabolism data, minimal renal excretion and a constant exposure was able to assess the bioaccumulative potential of a chemical. The approach has been analysed using literature data on well-known bioaccumulative compounds and liver metabolism data from the ECVAM database and a subset of the ToxCast phase I chemical library-in total 94 compounds covering pharmaceuticals, plant protection products and industrial chemicals. Our results provide further evidence that partitioning properties do not allow for a reliable screening criteria for human chemical hazard. Our model, based on a 100% intestinal absorption assumption, suggests that metabolic clearance, plasma protein-binding properties and renal excretion are the main factors in determining whether bioaccumulation will occur and its amount. It is essential that in vitro metabolic clearance tests with metabolic competent cell lines as well as plasma protein-binding assays be performed for suspected bioaccumulative compounds. PMID- 22089527 TI - Fallopian tube correlates of ovarian serous borderline tumors. AB - Ovarian serous borderline tumors (SBTs) are presumed to originate in the ovarian cortex or peritoneal surface. The pathogenetic role of the fallopian tube (FT) is unclear; however, recently, secretory cell outgrowths (SCOUTs) lacking PAX2 expression were described in benign FTs. This study addressed (1) the differentiation characteristics of SBTs and (2) the frequency of SCOUTs lacking PAX2 expression in the FTs of patients with SBTs and compared (3) SCOUT morphology and (4) PAX2 expression with SBTs. SBTs and FT epithelium shared both ciliated (p73) and secretory (HMFG2) differentiation. PAX2-null SCOUT frequency in FT cross-sections from patients with SBTs was 0.28 (110 of 398) versus 0.112 in benign hysterectomies and nearly 0 in pediatric and postpartum sterilization specimens (P = < 0.001). When adjusted for age, the differences narrowed but remained significant (P = 0.010). SCOUTs were heterogeneous, some displaying ciliated differentiation and papillary architecture. Two cases of discrete multifocal papillary SCOUTs in the FTs were associated with SBTs. All SBTs had heterogeneous PAX2 staining with areas of PAX2 loss. This study shows for the first time that PAX2-null SCOUTs are more common in the oviducts of women with SBTs and that loss of PAX2 expression occurs in most SBTs. These discoveries link both morphologic and functional gene (PAX2) alterations in the oviduct to SBTs, similar to that reported in high-grade serous carcinoma. Further study is warranted to clarify the relationship of the oviduct to serous neoplasia. PMID- 22089526 TI - Asymmetry of 13C labeled 3-pyruvate affords improved site specific labeling of RNA for NMR spectroscopy. AB - Selective isotopic labeling provides an unparalleled window within which to study the structure and dynamics of RNAs by high resolution NMR spectroscopy. Unlike commonly used carbon sources, the asymmetry of (13)C-labeled pyruvate provides selective labeling in both the ribose and base moieties of nucleotides using Escherichia coli variants, that until now were not feasible. Here we show that an E. coli mutant strain that lacks succinate and malate dehydrogenases (DL323) and grown on [3-(13)C]-pyruvate affords ribonucleotides with site specific labeling at C5' (~95%) and C1' (~42%) and minimal enrichment elsewhere in the ribose ring. Enrichment is also achieved at purine C2 and C8 (~95%) and pyrimidine C5 (~100%) positions with minimal labeling at pyrimidine C6 and purine C5 positions. These labeling patterns contrast with those obtained with DL323 E. coli grown on [1, 3 (13)C]-glycerol for which the ribose ring is labeled in all but the C4' carbon position, leading to multiplet splitting of the C1', C2' and C3' carbon atoms. The usefulness of these labeling patterns is demonstrated with a 27-nt RNA fragment derived from the 30S ribosomal subunit. Removal of the strong magnetic coupling within the ribose and base leads to increased sensitivity, substantial simplification of NMR spectra, and more precise and accurate dynamic parameters derived from NMR relaxation measurements. Thus these new labels offer valuable probes for characterizing the structure and dynamics of RNA that were previously limited by the constraint of uniformly labeled nucleotides. PMID- 22089528 TI - Pravastatin inhibits C-reactive protein generation induced by fibrinogen, fibrin and FDP in isolated rat vascular smooth muscle cells. AB - OBJECTIVE: The available evidence indicates that C-reactive protein (CRP) participates directly in atherosclerosis formation as an inflammatory molecule. Our previous investigation suggested that fibrinogen, fibrin and fibrinogen degradation products (FDP) produce a pro-inflammatory effect on vascular smooth muscle cells (VSMCs) through inducing CRP generation. In the present study, we observed the effect of pravastatin on CRP generation induced by fibrinogen, fibrin and FDP in rat VSMCs. METHODS: VSMCs from Sprague-Dawley rats were cultured. Fibrinogen, fibrin and FDP were used as stimulants for CRP generation. VSMCs were preincubated with pravastatin at 10, 30, 100 MUM for 30 min prior to stimulation. CRP mRNA expression was studied by reverse transcription polymerase chain reaction (RT-PCR). CRP levels in the supernatant of VSMCs were measured by enzyme-linked immunosorbent assay (ELISA). CRP expression in VSMCs was examined with immunocytochemical staining. RESULTS: ELISA analysis showed that the pravastatin concentration-dependently reduced fibrinogen-, fibrin- and FDP stimulated generation of CRP in VSMCs, with maximal inhibition of 56.6, 55.7 and 62.3%, respectively. Immunocytochemical staining and RT-PCR revealed that pravastatin inhibited protein and mRNA expression of CRP in VSMCs significantly. CONCLUSIONS: Pravastatin at the concentrations used in the present experiment has ability to relieve vascular inflammation and to restrain atherosclerotic processes via inhibiting the CRP production induced by fibrinogen, fibrin and FDP in VSMCs, which helps explain the beneficial effects of pravastatin on atherosclerosis. PMID- 22089530 TI - Dephasing effect on transport of a graphene p-n junction in a quantum Hall regime. AB - The influence of the dephasing effect on the conductance distribution of disordered graphene p-n junctions is studied. Without the dephasing, the conductance distribution has a very wide range and the conductance fluctuation is large. In this case, the conductance plateaus cannot be obtained in a single sample with the fixed disorder configuration. However, by introducing the dephasing, we find that the distribution becomes narrow dramatically and the fluctuation is suppressed strongly, so that the conductance plateaus are obtained clearly for one single sample, which is consistent with experimental measurements. Furthermore, we also investigate the scaling feature of the conductance distribution and find that it has good scaling behavior in the strong dephasing case. PMID- 22089529 TI - Associations between interleukin-23R polymorphisms and ankylosing spondylitis susceptibility: a meta-analysis. AB - OBJECTIVE: The aim of this study was to determine whether interleukin-23R (IL 23R) polymorphisms confer susceptibility to ankylosing spondylitis (AS). METHODS: The authors conducted meta-analyses on associations between IL-23R polymorphisms and AS susceptibility, using fixed and random effects models. RESULTS: A total of 10 studies (14 separate comparisons) were included in this meta-analysis, which included European and Asian populations. Meta-analysis revealed a significant association between AS and the two alleles of rs11209032 polymorphism in all study subjects (OR = 1.182, 95% CI 1.120-1.249, P = 0.000). Stratification by ethnicity identified a significant association between this polymorphism and AS in the European (OR = 1.234, 95% CI 1.159-1.313, P = 0.000), but not in the Asian populations (OR = 1.030, 95% CI 0.921-1.152, P = 0.608). Meta-analyses of rs1004819, rs10489629, rs1343151, rs1495965, and rs2201841 polymorphisms showed the same pattern as that shown by rs11209032 meta-analysis. Meta-analysis also revealed a significant association between the two alleles of the rs11209026 and the rs11465804 polymorphisms and the risk of developing AS in Europeans. Interestingly, the rs7517847 polymorphism was found to be significantly associated with AS susceptibility in both Europeans and Asians. CONCLUSIONS: This meta-analysis shows that the IL-23R polymorphisms are associated with the development of AS in Europeans. PMID- 22089531 TI - Influence of the uterine environment on the development of in vitro-produced equine embryos. AB - The necessity for early interaction between the embryo and the oviductal and/or uterine environment in the horse is reflected by several striking differences between equine embryos that develop in vivo and those produced in vitro. Better understanding of the salient interactions may help to improve the efficiency of in vitro equine embryo production. In an initial experiment, cleavage-stage in vitro-produced (IVP) equine embryos were transferred into the uterus of recipient mares that had ovulated recently to determine whether premature placement in this in vivo environment would improve subsequent development. In a second experiment, an important element of the uterine environment was mimicked by adding uterocalin, a major component of the endometrial secretions during early pregnancy, to the culture medium. Intrauterine transfer of cleavage-stage IVP equine embryos yielded neither ultrasonographically detectable pregnancies nor day 7 blastocysts, indicating that the uterus is not a suitable environment for pre-compact morula stage horse embryos. By contrast, exposure to uterocalin during IVP improved capsule formation, although it did not measurably affect the development or expression of a panel of genes known to differ between in vivo and in vitro embryos. Further studies are required to evaluate whether uterocalin serves purely as a carrier protein or more directly promotes improved capsule development. PMID- 22089532 TI - Novel mechanism of angiotensin II-induced cardiac injury in hypertensive rats: the critical role of ASK1 and VEGF. AB - This study was undertaken to elucidate a novel mechanism underlying angiotensin II-induced cardiac injury, focusing on the role of oxidative stress and myocardial capillary density. Salt-loaded Dahl salt-sensitive hypertensive rats (DS rats), a useful model for hypertensive cardiac remodeling or heart failure, were orally given irbesartan (an AT1 receptor blocker), tempol (a superoxide dismutase mimetic) or hydralazine (a vasodilator). Irbesartan significantly ameliorated left ventricular ischemia and prevented the development of cardiac hypertrophy and fibrosis in DS rats. The benefits were associated with the attenuation of oxidative stress, normalization of myocardial capillary density and inhibition of capillary endothelial apoptosis. Moreover, DS rats with significant cardiac hypertrophy and fibrosis displayed decreased myocardial vascular endothelial growth factor (VEGF) expression and increased cardiac apoptosis signal-regulating kinase 1 (ASK1) activation. Treatment with irbesartan significantly reversed these phenotypes. Tempol treatment of DS rats mimicked all the above-mentioned effects of irbesartan, indicating the critical role of oxidative stress in cardiac injury. We also investigated the role of VEGF and ASK1 in oxidative stress-induced endothelial apoptosis by using cultured endothelial cells from wild-type and ASK1-deficient mice. Oxidative stress induced ASK1 activation led to endothelial apoptosis, and VEGF treatment prevented oxidative stress-induced endothelial apoptosis by inhibiting ASK1 activation. We obtained the first evidence that oxidative stress-induced cardiac VEGF repression and ASK1 activation caused the enhancement of endothelial apoptosis and contributed to a decrease in myocardial capillary density. These effects resulted in angiotensin II-induced progression of cardiac injury. PMID- 22089533 TI - Individual and neighborhood social factors of hypertension management in a low socioeconomic status population: a community-based case-control study in Singapore. AB - The aim of this study was to determine hypertension awareness, treatment and control, as well as to carry out regular blood pressure (BP) screening and monitoring, in a multi-ethnic urban low-socioeconomic status (SES) Asian community; and to compare these estimates with those of a higher-SES community in the same geographic location. We studied a neighborhood of three blocks of rented public flats (lower-SES community) and three adjacent blocks of owner-occupied public flats (higher-SES community) in Taman Jurong, Singapore. BP was measured, and demographic details and reasons for irregular BP screening, monitoring and treatment were collected from 2009 to 2010. Logistic regression was used to determine predictors of hypertension management. Participation was 90.0% (359/400) for the rental flat community and 70.2% (351/500) for the owner occupied flats. Prevalence, awareness, treatment and control in the low-SES community (rental flats) were 63.9% (228/357), 61.8% (141/228), 69.5% (98/141) and 43.9% (43/98), respectively, whereas in the neighboring community these were 65.0% (228/351), 83.3% (190/228), 85.3% (162/190) and 66.0% (107/162), respectively. Adjusting for other sociodemographic variables, awareness, treatment and control were poorer in the low-SES community. In the low-SES community, awareness was higher among diabetics, dyslipidemics, those >=60 years and those with regular access to doctors. Treatment was more likely among those >=60 years, but less likely among those needing financial aid. Control was less likely in the employed. High cost of screening and treatment, if diagnosed, was the most frequently cited barrier among the low-SES group. Hypertension management in those of lower SES is poorer than in those of higher SES. For the lower-SES population, financial barriers need to be addressed. PMID- 22089535 TI - Aliskiren reduced renal fibrosis in mice with chronic ischemic kidney injury- beyond the direct renin inhibition. AB - Chronic renal ischemia leads to renal fibrosis and atrophy. Activation of the renin-angiotensin-aldosterone system is one of the main mechanisms driving chronic renal ischemic injury. The aim of the present study was to define the effect of aliskiren in chronic ischemia of the kidney. Two-kidney, one-clip mice were used to study chronic renal ischemia. Aliskiren significantly lowered the blood pressure in mice with renal artery constriction (92.1+/-1.1 vs. 81.0+/-1.8 mm Hg, P<0.05). Renin expression was significantly increased in ischemic kidneys when treated with aliskiren. In addition, (Pro)renin receptor expression was decreased by aliskiren in ischemic kidneys. Aliskiren treatment significantly increased klotho expression and reduced the expression of fibrogenic cystokines, caspase-3 and Bax in ischemic kidneys. Histological examination revealed that aliskiren significantly reduced the nephrosclerosis score (4.5+/-1.9 vs. 7.3+/ 0.4, P<0.05). Immunofluorescence staining also showed that aliskiren decreased the deposition of interstitial collagen I in ischemic kidneys. In conclusion, direct renin inhibition significantly reduced renal fibrosis and apoptosis following chronic renal ischemia. PMID- 22089534 TI - Optimal Combination of Effective ANtihypertensives (OCEAN) study: a prospective, randomized, open-label, blinded endpoint trial--rationale, design and results of a pilot study in Japan. AB - There are limited clinical trials examining the efficacy of antihypertensive drug combinations aimed at preventing cardiovascular events. Therefore, we designed a randomized controlled trial using amlodipine as the base drug of a multi-drug regimen, the Optimal Combination of Effective ANtihypertensives (OCEAN) Study, to determine the drug combination that is most efficacious in the prevention of cardiovascular events, such as stroke. The OCEAN Study is a collaborative study between Japan and China, enrolling 20 000 patients and following them for 3 to 4 years. A pilot study was conducted before the full-scale study to confirm the feasibility of the protocol and that the study groups and infrastructures could function properly. A total of 279 Japanese patients were enrolled from 57 participating medical institutions between June and December 2004. Two hundred and sixty-six patients (mean age: 65.9 years) were treated with amlodipine alone. One hundred and fifty-four of these patients (57.9%) did not reach the treatment targets (<140/90 mm Hg for the elderly and patients with cerebrovascular disease, <130/80 mm Hg for those with diabetes mellitus, chronic kidney disease or prior myocardial infarction) and a second agent was added. They were randomly allocated into three different treatment groups using a diuretic, a beta-blocker or an angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist. The pilot study showed that the protocol was appropriate, and the inclusion of patients with slightly higher blood pressures was necessary to increase the randomization rate. It also confirmed that we organized properly functioning study groups and infrastructures. PMID- 22089536 TI - Sex-related differences in pharmacokinetics and pharmacodynamics of anti hypertensive drugs. AB - Sex-specific differences in pharmacokinetics and pharmacodynamics have been reported to have important clinical consequences. In this review, some representative sex-specific differences in absorption and transporters (that is, P-glycoprotein (P-gp)), metabolic processes (that is, those that involve cytochrome P450 (CYP)), clearance (Cl) processes (for example, renal excretion or other pharmacokinetic parameters) and involvement of sex hormones (that is, estrogen and testosterone) in the regulation of some metabolic enzymes are introduced for each of the following categories of anti-hypertensive drugs: calcium-channel blockers, angiotensin-receptor blockers and angiotensin converting enzyme inhibitors, diuretic agents, and beta-adrenergic-receptor blockers (beta-blockers). In many cases, female sex is a risk factor for adverse effects or attenuated clinical responses because of lower Cl, smaller distribution volumes, higher activity of some metabolic enzymes (especially hepatic CYP3A4), or presence of sex hormones. Additionally, some of these factors often co-contribute to the sex-specific differences. Furthermore, pharmacodynamic variability among individuals is often larger than pharmacokinetic variability; in other words, it could become a predominant determinant of interindividual differences in therapeutic responses. Thus, studies of sex-specific differences in pharmacokinetics and pharmacodynamics should be conducted. However, sex related disparities in pharmacokinetics may not necessarily correspond to clinically significant differences in therapeutic response. There are still large gaps in our knowledge of sex-specific differences in clinical pharmacology and much more research is needed. PMID- 22089537 TI - Use of home sphygmomanometers in Turkey: a nation-wide survey. AB - The purposes of this study were to detect the prevalence of ownership of a home sphygmomanometer among hypertensive subjects through a nation-wide survey, to investigate parameters affecting ownership of a sphygmomanometer, to compare how home blood pressure monitoring (HBPM) was actually used in daily practice with some aspects of the current guidelines, and to discuss what we implemented to increase the reliability of HBPM in a developing country. A total of 2747 hypertensive patients from 34 cities, representative of the Turkish population, were enrolled in the study. A multiple-choice questionnaire was administered to each participant using the computer-assisted telephone interviewing method. Among 2747 hypertensive patients, 1281 of them (46.6%) had a home sphygmomanometer. Most of the patients were using wrist devices. The factors associated with ownership of a sphygmomanometer were female gender, older age, obesity, higher educational status, higher income level, living in urban areas, awareness of hypertension and anti-hypertensive drug usage. Only 16% of the devices were used on the advice of a physician. The patients learned usage of their device mainly from the sellers and their relatives. The ownership of a home sphygmomanometer is common among hypertensive patients in Turkey, but regular monitoring of blood pressure before physician visits is rare despite common ownership of these devices. Daily practice of HBPM in Turkey was far from the recommendations of the current guidelines. More effort is needed to improve the reliability of HBPM. PMID- 22089538 TI - A metabonomic study of biochemical changes characteristic of genetically hypertensive rats based on (1)H NMR spectroscopic urinalysis. AB - Spontaneously hypertensive rats (SHR) provide a simple model for studying essential hypertension. Their genetic and metabolic features are of great interest because they may provide insights into the pathophysiological processes underlying essential hypertension. We have thus investigated the metabolic characteristics of SHR at various ages, covering the prehypertensive stage and the developmental phase of hypertension, using a (1)H nuclear magnetic resonance (NMR)-based metabonomic approach. Twenty-four-hour urine samples from the SHR and their age-matched normotensive control, Wistar-Kyoto rats, were analyzed using (1)H NMR spectroscopy, and the spectral data were subjected to principal components analysis (PCA) to find metabolic differences between the two strains. Consequently, it was possible to separate the urine samples between the two strains at any age ranging from 4 to 20 weeks in the principal component scores plots. The major spectral regions and signals (metabolites) contributing to the separation were picked up based on the loadings. Subsequently, the urinary excreted levels of metabolites highlighted by the PCA were compared based on the signal intensities corrected by urine volume and body weight. These investigations revealed the major metabolic changes characteristic of the SHR, which included differences in citrate, alpha-ketoglutarate, succinate, hippurate, phenylacetylglycine, p-cresol glucuronide, creatine, taurine, medium-chain dicarboxylates (tentative), unknown (delta 3.11), and the regions at 3.60, 3.64, 3.68 and 3.88 p.p.m. The results supported the occurrence of metabolic acidosis in the SHR in the period of prehypertension as well as rapidly rising blood pressure. In addition, the intestinal microfloral populations in the SHR were suggested to be altered in the developmental phase of hypertension. PMID- 22089539 TI - Beta-blocker migraine prophylaxis affects the excitability of the visual cortex as revealed by transcranial magnetic stimulation. AB - The objective of this study is to assess effects of beta-blocker migraine prophylaxis on cortical excitability determined by transcranial magnetic stimulation (TMS). Phosphene and motor thresholds (PT, MT) were investigated in 29 patients with migraine, in 15 of them prior to and following preventive medication with metoprolol and in 14 patients without prophylaxis. Following prophylaxis headache frequency significantly decreased (p = 0.005) and mean PT were significantly increased (51.5 +/- 7.5 vs. 63.6 +/- 8.4%) compared to patients without preventive treatment (53.7 +/- 5.3 vs. 52.3 +/- 6.3%; p = 0.040). Mean MT did not significantly differ either between groups or due to treatment. In the group of all patients, a significant inverse correlation between headache frequency and the level of PT was found (R = -0.629; p < 0.01). There was, however, no significant correlation in the subgroups of patients. We conclude that (a) clinical efficacy of beta-blocker treatment in migraine could be (at least partly) linked to its ability to modulate the excitability of the visual cortex and (b) the PT determined by TMS appears suitable to assess the effects of prophylaxis on cortical excitability in the individual patient. This may be useful in clinical trials investigating migraine preventive drugs. PMID- 22089540 TI - Colloidal mercury (Hg) distribution in soil samples by sedimentation field-flow fractionation coupled to mercury cold vapour generation atomic absorption spectroscopy. AB - Diverse analytical techniques are available to determine the particle size distribution of potentially toxic elements in matrices of environmental interest such as soil, sediments, freshwater and groundwater. However, a single technique is often not exhaustive enough to determine both particle size distribution and element concentration. In the present work, the investigation of mercury in soil samples collected from a polluted industrial site was performed by using a new analytical approach which makes use of sedimentation field-flow fractionation (SdFFF) coupled to cold vapour generation electrothermal atomic absorption spectroscopy (CV-ETAAS). The Hg concentration in the SdFFF fractions revealed a broad distribution from about 0.1 to 1 MUm, roughly following the particle size distributions, presenting a maximum at about 400-700 nm in diameter. A correlation between the concentration of Hg in the colloidal fraction and organic matter (O.M.) content in the soil samples was also found. However, this correlation is less likely to be related to Hg sorption to soil O.M. but rather to the presence of colloidal mercuric sulfide particles whose size is probably controlled by the occurrence of dissolved O.M. The presence of O.M. could have prevented the aggregation of smaller particles, leading to an accumulation of mercuric sulfides in the colloidal fraction. In this respect, particle size distribution of soil samples can help to understand the role played by colloidal particles in mobilising mercury (also as insoluble compounds) and provide a significant contribution in determining the environmental impact of this toxic element. PMID- 22089541 TI - Balint syndrome and visual allochiria in a patient with reversible cerebral vasoconstriction syndrome. AB - Balint syndrome (simultagnosia, optic ataxia, and ocular apraxia) is typically caused by pathology affecting the parietal-occipital regions bilaterally. Visual allochiria is an uncommonly reported symptom associated with parietal lobe pathology in which visual stimuli presented to one hemispace are transposed to the opposite side. We describe a patient with Balint syndrome and visual allochiria whose initial brain MRI demonstrated acute infarction of the right parietal-occipital region. Repeat imaging 9 days later revealed bilateral parietal-occipital infarctions consistent with the observed clinical syndrome. Reversible cerebral vasoconstriction syndrome is introduced as a novel cerebrovascular etiology of Balint syndrome. PMID- 22089542 TI - Effect of CpG island methylation on microRNA expression in the k-562 cell line. AB - To test the hypothesis that methylation of a CpG island is associated with regulation of microRNA expression, we investigated CpG islands in the upstream sequences of microRNA precursors (pre-miRNAs) through bioinformatic analysis and determined whether the CpG islands were methylated by methylation-specific PCR in the k-562 cell line. We used 5-azacytidine for DNA demethylation, and changes in microRNA expression were detected by microarray assay, RT-PCR, and real-time PCR after 5-azacytidine induction. We showed that the CpG islands in the upstream regions of 18 pre-miRNAs were methylated, including miR-663, miR-369, miR-615, and miR-410, and promoter activity was detected in the upstream region of pre-miR 663. We found that a decrease in methylation of a CpG island could up-regulate the expression of miR-663, suggesting that miR-663 could be regulated by DNA methylation. Expression levels of miR-369, miR-615, and miR-410 were not regulated by DNA methylation in this cell line. PMID- 22089543 TI - Genome characterization of a breeding line derived from a cross between Oryza sativa and Oryza rufipogon. AB - A preliminary screening was conducted on BC3F1 and BC4F1 backcross families developed from crossing Oryza sativa (MR219) and O. rufipogon (IRGC105491). Despite earlier results showing that O. rufipogon alleles (wild introgression) contributed to both number of panicles (qPPL-2) and tillers (qTPL-2) at loci RM250, RM208, and RM48 in line A20 of the BC2F2 population, we observed that wild introgression was lost at loci RM250 and RM208 but retained at locus RM48 in BC3F1 and BC4F1. Progeny tests conducted utilizing genotype and phenotype data on both BC4F1 and a reference population, BC2F7 (A20 line), did not show significant differences between groups having the MR219 allele and wild introgression at locus RM48. This suggests that there is no additive and transgressive effect of wild introgression in the BC3F1 and BC4F1 generated. The presence of wild introgression was largely due to gene contamination by cross-pollination during field breeding practices. PMID- 22089545 TI - Parthenogenetic embryonic stem cells with H19 siRNA-mediated knockdown as a potential resource for cell therapy. AB - Embryonic stem (ES) cells are used in cell therapy and tissue engineering due to their ability to produce different cells types. However, studies of ES cells that are derived from fertilized embryos have raised concerns about the limitations imposed by ethical and political considerations. Therefore, many studies of stem cells use the stem cells that are derived from unfertilized oocytes and adult tissue. Although parthenogenetic embryonic stem (ESP) cells also avoid ethical and political dilemmas and can be used in cell-based therapy, the ESP cells exhibit growth retardation problems. Therefore, to investigate the potential for muscle growth from genetically modified ESP cells, we established four ES cell types, including normal embryonic stem (ESN) cells, ESP cells, ESP cells that overexpress the insulin-like growth factor 2 (Igf2) gene (ESI) and ESP cells with down-regulated H19 gene expression (ESH). Using these cells, we examined the expression profiles of genes that were related to imprinting and muscle using microarrays. The gene expression patterns of ESI and ESH cells were similar and were more closely related to the ESN pattern than that of the ESP cells. Differentiated ESH cells exhibited increased expression of bone morphologic protein 4 (BMP4), which is a mesoderm marker, compared with the differentiated ESI cells. We showed that Igf2 expression was induced by H19 silencing in the ESP cells via hypermethylation of the H19 imprinting control region 1 (ICR1). Moreover, the proportion of ESH-derived chimera was slightly higher than those produced from the ESP cells. In addition, we detected increased cell proliferation in the MEF cells following H19 knock-down. These results indicate that the ESH cells may be a source of cell-based therapy for conditions such as muscular atrophy. PMID- 22089546 TI - Tin oxide-surface modified anatase titanium(IV) dioxide with enhanced UV-light photocatalytic activity. AB - [Sn(acac)(2)]Cl(2) is chemisorbed on the surfaces of anatase TiO(2)via ion exchange between the complex ions and H(+) released from the surface Ti-OH groups without liberation of the acetylacetonate ligand (Sn(acac)(2)/TiO(2)). The post heating at 873 K in air forms tin oxide species on the TiO(2) surface in a highly dispersed state on a molecular scale ((SnO(2))(m)/TiO(2)). A low level of this p block metal oxide surface modification (~0.007 Sn ions nm(-2)) accelerates the UV light-activities for the liquid- and gas-phase reactions, whereas in contrast to the surface modification with d block metal oxides such as FeO(x) and NiO, no visible-light response is induced. Electrochemical measurements and first principles density functional theory (DFT) calculations for (SnO(2))(m)/TiO(2) model clusters (m = 1, 2) indicate that the bulk (TiO(2))-to-surface interfacial electron transfer (BS-IET) enhances charge separation and the following electron transfer to O(2) to increase the photocatalytic activity. PMID- 22089547 TI - Plasmonic black-hole: broadband omnidirectional absorber of gap surface plasmons. AB - Using the effective-index approximation we show that touching spherical metal surfaces form a broadband omnidirectional absorber of gap surface plasmons (GSP), concentrating all GSP waves travelling within a certain radius at the point of contact (at which the field intensity tends to infinity even in the presence of metal absorption) and representing thereby a two-dimensional analogue of an optical black-hole realized without use of metamaterials. The developed wave analysis is supplemented with the geometrical optics (adiabatic) description providing explicit expressions for the critical radius (radius of the event horizon) and buildup of field enhancement along ray trajectories. PMID- 22089548 TI - Higher-order cross-correlation-based Doppler optical coherence tomography. AB - A method based on higher-order cross-correlation is proposed to fetch the Doppler information on flow velocity within areas under low signal-to-noise ratio (SNR) by spectral domain optical coherence tomography. The proposed method is theoretically developed and validated by measurement of a moving mirror with known velocities. Standard deviations of flow velocities of the mirror under different SNRs are determined by the proposed method and compared with those by the modified phase-resolved method. Measurement of flowing particles within a glass capillary is also conducted, and Doppler flow velocity maps of the glass capillary are reconstructed by both methods. All experimental results demonstrate that the proposed method can significantly suppress noise, thus rendering it suitable for flow measurement under low SNR cases. PMID- 22089549 TI - Fast Fourier domain localization algorithm of a single molecule with nanometer precision. AB - We present an algorithm to determine the location of a fluorescent molecule with nanometer-scale accuracy. A Fourier domain localization scheme based on zero padded fast Fourier transform and phase gradient operators is used to obtain a powerful mathematical model for localizing the molecule without numerical fitting. Compared with conventional algorithms, our position estimator does not require prior background information or initial parameter estimation. Numerical simulations indicate that the proposed method exhibits high localization precision and small bias while executing almost as fast as the fluoroBancroft algorithm. PMID- 22089550 TI - DFB fiber laser hydrophone with band-pass response. AB - A distributed-feedback fiber laser hydrophone with band-pass response is presented. The design of the hydrophone aims to equalize static pressure and eliminate signal aliasing of high-frequency acoustic components. Theoretical analysis is presented based on electro-acoustic theory. The experimental results agree well with the theory. The measured underwater responses show that the hydrophone has a pressure sensitivity of -170 dB re:pm/MUPa over a bandwidth between 100 Hz and 500 Hz. A sensitivity reduction exceeding -35 dB is observed at 2500 Hz. The tested static pressure sensitivity of the hydrophone is -226 dB. The proposed fiber laser hydrophone of this kind is expected to have important application in deep water fiber-optic sonar systems with anti-aliasing, and the understanding gained through this work can be extended to a guide of hydrophone design for required filtering bandwidth. PMID- 22089551 TI - Stability of solitons in parity-time-symmetric couplers. AB - Families of analytical solutions are found for symmetric and antisymmetric solitons in a dual-core system with Kerr nonlinearity and parity-time (PT) balanced gain and loss. The crucial issue is stability of the solitons. A stability region is obtained in an analytical form, and verified by simulations, for the PT-symmetric solitons. For the antisymmetric ones, the stability border is found in a numerical form. Moving solitons of both types collide elastically. The two soliton species merge into one in the "supersymmetric" case, with equal coefficients of gain, loss, and intercore coupling. These solitons feature a subexponential instability, which may be suppressed by periodic switching ("management"). PMID- 22089552 TI - 40 Gb/s, secure optical communication based upon fast reconfigurable time domain spectral phase en/decoding with 40 Gchip/s optical code and symbol overlapping. AB - We propose and experimentally demonstrate a 40 Gb/s secure optical communication system with on-off-keying (OOK) modulation format by using a time domain spectral phase en/decoding scheme, which employs a highly dispersive element and high speed phase modulator for introducing significant symbol overlapping for both the encoded and incorrectly decoded noiselike signals to enhance the information security against eavesdropping using a power detector. The influence of dispersion and chip modulation rate on the symbol overlapping of the incorrectly decoded signal has been analytically investigated and experimentally verified. Security enhancement for 40 Gb/s OOK data using fast reconfigurable 40 Gchip/s optical codes with code lengths of up to 1024 has been demonstrated and compared with a 10 Gb/s system. PMID- 22089553 TI - Revisiting the normalized Born approximation: effects of scattering. AB - The normalized Born approximation has been suggested as a ratiometric method in fluorescence molecular tomography (FMT) applications, to account for heterogeneity variations. The method enabled practical inversions, as it offered fluorescence reconstruction accuracy over a wide range of absorption heterogeneity, while also accounting for unknown experimental factors, such as the various system gains and losses. Yet it was noted that scattering variations affect the robustness and accuracy. Herein we decompose the effects of absorption and scattering and capitalize on the recent development of hybrid FMT/x-ray computed tomography imaging methods to proposed amendments to the method, which improve the overall accuracy of the approach. PMID- 22089554 TI - Role of the phase in the identification of delay time in semiconductor lasers with optical feedback. AB - We consider a semiconductor laser with external optical feedback operating at a regime for which the delay time signature is extremely difficult to identify from the analysis of the intensity time series, using standard techniques. We show that such a delay signature can be successfully retrieved by computing the same quantifiers from the phase, the real or the imaginary part of the field, even in the presence of noise. Therefore, the choice of the observable is the determinant for parameter identification. PMID- 22089555 TI - Superoscillatory diffraction-free beams. AB - It is theoretically shown that by superimposing diffraction-free solutions of the Helmholtz equation, one can construct localized diffraction-free beams that pass through predetermined points on subwavelength distances. These beams are based on the phenomenon of superoscillations and thus do not contain any evanescent waves. The effect of an aperture and noise is examined in specific examples where truncated beams with lambda/3 subwavelength features can propagate into the far field. PMID- 22089556 TI - Signal restoration in intensity-modulated optical OFDM access systems. AB - It is well known that deliberate signal clipping in an intensity-modulated (IM) laser transmitter helps to overcome the optical orthogonal frequency division multiplexing (OFDM) system performance limitation that is related to the signal high peak-to-average power ratio. The amplitude of a clipped OFDM signal has to be optimized in order to minimize the optical power that is required to achieve a specified system performance. However, the signal clipping introduces nonlinear distortion (so-called clipping noise) and leads to a system performance penalty. In this Letter, the performance of the IM optical OFDM system with digital baseband clipping distortion in the transmitter and clipping noise compensation by means of signal restoration in the digital signal processing unit of the system receiver is analytically evaluated. It is demonstrated that the system bit error ratio can be reduced by more than an order of magnitude, from 10(-3) to 3.5*10(-5), by applying only the first iteration of the signal restoration algorithm proposed in this Letter. The results of the analytical analysis are verified with brute-force numerical simulations based on direct error counting. PMID- 22089557 TI - Emergence of Anderson localization in plasmonic waveguides. AB - The propagation of surface plasmon polaritons in dielectric loaded waveguides with randomly placed scatterers is studied using both numerical simulations and a simplified transfer matrix framework. Despite the importance of losses in this system, we find fingerprints of the localized behavior of one-dimensional disordered systems. Furthermore, losses amplify the impact of the necklace states on the transport properties for systems not much larger than the localization length. The system presented here also offers the possibility to use localization effects for engineering purposes by means of deliberately introduced disorder. PMID- 22089558 TI - Simple design of an edge-emitting diode laser for preventing spatial multimoding via thermal lensing. AB - The parameters of a diode-laser structure composed of a pair of built-in high index regions for providing stable, single-spatial-mode operation to high cw powers are numerically found. A three-dimensional numerical code has been implemented that takes into account carrier diffusion in the quantum well and thermal lensing. The laser characteristics are calculated as functions of the above-threshold drive level. Within the simulation, higher-order optical modes on a "frozen background" are computed via the Arnoldi algorithm. Then, for a 6-MUm wide low-index core and 2-3-mm-long devices, stable single-mode operation up to multiwatt-level (2-3 W) cw output power is predicted. PMID- 22089559 TI - Intense photoluminescence at 2.7 MUm in transparent Er 3+:CaF2-fluorophosphate glass microcomposite. AB - Er3+ doped CaF2-fluorophosphate (FP) glass microcomposites were produced by heat treating the mixture of Er3+:CaF2 precipitate and FP glass powder above the melting temperature of the FP glass. The appearance of CaF2 crystallites in the resulting composites was confirmed by x ray diffraction. Despite the fact that the average diameter of the crystallites was around 10 MUm as revealed by the micromorphology study, a transparent composite was obtained by matching the refractive index of FP glass to that of CaF2. Intense IR fluorescence at around 2.7 MUm was observed in the composite, implying the composite would be a promising candidate for IR lasers and amplifiers. PMID- 22089560 TI - Coherent backscattering by polydisperse discrete random media: exact T-matrix results. AB - The numerically exact superposition T-matrix method is used to compute, for the first time to our knowledge, electromagnetic scattering by finite spherical volumes composed of polydisperse mixtures of spherical particles with different size parameters or different refractive indices. The backscattering patterns calculated in the far-field zone of the polydisperse multiparticle volumes reveal unequivocally the classical manifestations of the effect of weak localization of electromagnetic waves in discrete random media, thereby corroborating the universal interference nature of coherent backscattering. The polarization opposition effect is shown to be the least robust manifestation of weak localization fading away with increasing particle size parameter. PMID- 22089561 TI - Ultraviolet and infrared photon-excited synergistic effect in Er3+-doped YbF3 phosphors. AB - A synergistic effect between UV down-conversion and IR up-conversion is witnessed in YbF3:Er3+ phosphors by employing the dual wavelength (369 nm and 980 nm) excitation source. The synergistic effect originates from an abnormal energy transfer between Er3+ ions, in which the Er3+ ions in metastable states excited by 369 nm photons are excited again by the 980 nm IR photons. The dual wavelength excited red emission intensity is 1.1 times the total red emission intensities from 369 nm and 980 nm single excitation. The synergistic effect refers us to a way to convert both high-energy and low-energy photons into one middle-energy photon with high quantum yield. PMID- 22089562 TI - Phase-to-phase and phase-to-amplitude transfer characteristics of a nondegenerate idler phase-sensitive amplifier. AB - For the first time to our knowledge, the phase-to-phase and phase-to-amplitude transfer functions of a nondegenerate-idler phase-sensitive fiber optic parametric amplifier are experimentally measured. Additionally, analytically and numerically obtained transfer curves show excellent agreement with the experimental curves. The experimental results were obtained by imposing a linear phase modulation onto the signal and idler wave simultaneously, and detecting the input and output signal using a self-homodyne coherent receiver. PMID- 22089563 TI - Unidirectional optical Bloch oscillations in asymmetric waveguide arrays. AB - We present an analytical proof of the existence of unidirectional optical Bloch oscillations in a waveguide array system. It is shown that the presence of nonreciprocity in the system allows for a complete normal-mode dephasing in one of the propagation directions, resulting in a unidirectional breakdown in Bloch oscillations. A model system consisting of an array of transversely magnetized asymmetric Si/SiO2 waveguides with a magneto-optic cover layer is presented. Large index contrasts between film and cover are critical for practical realizations. PMID- 22089564 TI - High-resolution quantitative phase microscopic imaging in deep UV with phase retrieval. AB - High-resolution three-dimensional (3D) microscopic imaging requires the use of short wavelengths. Quantitative 3D imaging techniques, such as digital holographic microscopy, require interference between the object beam and a known reference background for the extraction of phase information. At shorter wavelengths, due to short coherence lengths, it may be difficult to implement a two-beam off-axis setup. Thus, a single-beam technique, which provides complete phase information, may be better suited for short wavelengths. This Letter describes the development of a quantitative microscopy technique at 193 nm using multiple intensity samplings and phase retrieval. PMID- 22089565 TI - Optimal alignment sensing of a readout mode cleaner cavity. AB - Critically coupled resonant optical cavities are often used as mode cleaners in optical systems to improve the signal-to-noise ratio (SNR) of a signal that is encoded as an amplitude modulation of a laser beam. Achieving the best SNR requires maintaining the alignment of the mode cleaner relative to the laser beam on which the signal is encoded. An automatic alignment system that is primarily sensitive to the carrier field component of the beam will not, in general, provide optimal SNR. We present an approach that modifies traditional dither alignment sensing by applying a large amplitude modulation on the signal field, thereby producing error signals that are sensitive to the signal sideband field alignment. When used in conjunction with alignment actuators, this approach can improve the detected SNR; we demonstrate a factor of 3 improvement in the SNR of a kilometer-scale detector of the Laser Interferometer Gravitational-Wave Observatory. This approach can be generalized to other types of alignment sensors. PMID- 22089566 TI - A 2*2 spatial optical switch based on PT-symmetry. AB - We show a PT-symmetric coupler having an arm with a tunable gain and a no-loss arm when appropriately designed to possess reciprocal behavior, unlike its rivals having a fixed gain/loss arm, can perform as a tunable 2*2 spatial optical switch. The degree of the tunability equals the ratio of the coupler's length to the total coupling length. PMID- 22089567 TI - Domain-shape-based modulation of Cerenkov second-harmonic generation in multidomain strontium barium niobate. AB - We study experimentally and numerically the second-harmonic Cerenkov emission with two different characteristic azimuthal intensity distributions in strontium barium niobate with a random structure of chi2 nonlinearity. We monitor in situ the Cerenkov emission during domain switching and show that a change of domain size and shape results in a fourfold azimuthal modulation of the Cerenkov cone. PMID- 22089568 TI - Pump-enhanced optical parametric oscillator generating continuous wave tunable terahertz radiation. AB - We demonstrate a tunable cw terahertz (THz) parametric oscillator based on periodically poled MgO-doped lithium niobate, directly converting the 1030 nm pump wave into the THz regime. The tunability ranges from 1.2 to 2.9 THz at output power levels between 0.3 and 3.9 MUW. To overcome the high pump threshold caused by THz absorption in the nonlinear crystal, we employ an enhancement cavity with a finesse of 500 at the pump wavelength. The intracavity pump threshold at 1.4 THz is measured to be 350 W for a crystal length of 2.5 cm. PMID- 22089569 TI - Subpicosecond pulse generation from a 1.56 MUm mode-locked VECSEL. AB - Near-transform-limited subpicosecond pulses at 1.56 MUm were generated from an optically pumped InP-based vertical-external-cavity surface-emitting laser (VECSEL) passively mode-locked at 2 GHz repetition rate with a fast InGaAsNSb/GaAs semiconductor saturable absorber mirror (SESAM). The SESAM microcavity resonance was adjusted via a selective etching of phase layers specifically designed to control the magnitude of both the modulation depth and the intracavity group delay dispersion of the SESAM. Using the same VECSEL chip, we observed that the mode-locked pulse duration could be reduced from several picoseconds to less than 1 ps with a detuned resonant SESAM. PMID- 22089570 TI - Compact optical fiber curvature sensor based on concatenating two tapers. AB - A low-loss, compact, and highly sensitive optical fiber curvature sensor is presented. The device consists of two identical low-loss fused fiber tapers in tandem separated by a distance L. When the optical fiber is kept straight and fixed, no interference pattern appears in the transmitted spectrum. However, when the device is bent, the symmetry of the straight taper is lost and the first taper couples light into the cladding modes. In the second taper, a fraction of the total light guided by the cladding modes will be coupled back to the fundamental mode, producing an interference pattern in the transmitted spectrum. As the fiber device is bent, visibility of the interference fringes grows, reaching values close to 1. The dynamic range of the device can be tailored by the proper selection of taper diameter and separation between tapers. The effects of temperature and refractive index of the external medium on the response of the curvature sensor is also discussed. PMID- 22089571 TI - Utility transforms of optical fields employing deformable mirror. AB - Diffraction optical devices of modest degrees of freedom (DOF), such as deformable mirrors, have not been exploited as general-purpose transformers of optical fields. Described in this Letter is a method that guides deformable mirrors to optimal surfaces allowed by the DOF for various desirable outcomes. The method is based on a modal optimization procedure with the help of Walsh functions in controlling the variables of the mirrors, i.e. the actuators. It is shown that a deformable mirror of modest DOF can provide field transformations for arbitrary beam-splitting, formation of ring-shaped beams, and coherent beam combining. PMID- 22089572 TI - Shape of Fano resonance line spectra calculated for silver nanorods. AB - Using theoretical tools, we numerically demonstrated Fano line shapes in the scattering spectra of silver rods resulting from different mechanisms. One of the Fano line shapes is due to the coupling of an in-plane quadrupole and a dipole mode in a single rod. Two nodes were observed at the resonance wavelength, each of which is located at a quarter of the rod length from the two ends. The Fano resonance is strengthened when the silver rod is cut at the two nodal positions. The second mechanism that gives rise to a new Fano resonance peak occurs when the symmetry of the rod is broken and is a result of the asymmetric coupling between the two excited dipoles. PMID- 22089573 TI - Gradient enhanced third harmonic generation in a femtosecond filament. AB - The third harmonic generated during femtosecond filamentation in air is studied. By establishing a gradient from atmospheric pressure to vacuum conditions, we truncate the filament abruptly at defined positions. The introduction of the pressure gradient leads to an enhancement of the generated third harmonic radiation by 3 orders of magnitude. This effect is attributed to an improved on axis phase-matching condition. We investigate the spectral shape and the conversion efficiency of the third harmonic during the propagation in the filament. PMID- 22089574 TI - Stationary-fiber rotary probe with unobstructed 360 degrees view for optical coherence tomography. AB - A side-scanning fiber probe is a critical component for optical coherence tomography in medical imaging and diagnosis. We propose and fabricate an on-axis rotating probe that performs in situ, circumferential scanning that is shadow free (not susceptible to shadow effects caused by the motor's wires). A miniature motor that incorporates a bored-out shaft for the optical fiber is located at the distal end of the probe, which results in a more stable and uniform circumferential scan, free from wire-shadow interference effects. More importantly, this design, novel to our knowledge, compared to other probes avoids the insertion losses introduced by optical coupling components and the multitude of optical interfaces, which is very important for sensing weak signals backscattered from structures deep in the tissue. PMID- 22089575 TI - Application of dynamic line narrowing in resonant optical sensing. AB - We propose a dynamic operational mode and the resulting dynamic line narrowing as a method for enhancing the resolution and the detection limit of high-quality (high-Q) resonant optical sensors. Using a silica microtoroid as an experimental platform, we demonstrate that dynamic line narrowing through the thermo-optic effect can significantly improve the detection limit in both resonant shift and resonance splitting operating modes. PMID- 22089576 TI - Revealing the order of a vortex through its intensity record. AB - We show that the intensity distribution of an optical vortex contains information of its order. Specifically, the number of dark rings in the Fourier transform of the intensity is found to be equal to the order of the vortex. Based on this property and the orthogonality of Laguerre polynomials, we demonstrate the feasibility of an experimental technique for determining the order of optical vortices. It shows the beauty of going to complementary spaces, which has been employed earlier also to find the information not available in other domains. PMID- 22089577 TI - 50 dB parametric on-chip gain in silicon photonic wires. AB - A pulsed mid-infrared pump at lambda=2173 nm is used to demonstrate wideband optical parametric gain in a low-loss 2 cm long silicon photonic wire. Using dispersion engineering to obtain negative second-order (beta2) and positive fourth-order (beta4) dispersion, we generate broadband modulation instability and parametric fluorescence extending from 1911 nm-2486 nm. Using a cw probe signal to interrogate the modulation instability spectrum, we demonstrate parametric amplification >40 dB with an on-chip gain bandwidth wider than 580 nm, as well as narrowband Raman-assisted peak gain >50 dB. PMID- 22089578 TI - Diffraction grating with suppressed zero order fabricated using dielectric forces. AB - An electric-field-assisted method to produce diffractive optical devices is demonstrated. A uniform film of liquid UV curable resin was produced as a drying ring from an organic solvent. Dielectrophoresis forces maintained the stability of the thin film and also imprinted a periodic corrugation deformation of pitch 20 MUm on the film surface. Continuous in situ voltage-controlled adjustment of the optical diffraction pattern was carried out simultaneously with UV curing. A fully cured solid phase grating was produced with the particular voltage-selected tailored optical property that the zero transmitted order was suppressed for laser light at 633 nm. PMID- 22089579 TI - Anticolliding design for monolithic passively mode-locked semiconductor lasers. AB - The performance of two-section, passively mode-locked semiconductor lasers is theoretically analyzed for different cavity designs. Placing the saturable absorber section close to an antireflection-coated facet leads to a substantial increase in output power and a reduction in amplitude and timing jitter. Moreover, it broadens the bias current region of stable passive mode-locking operation. PMID- 22089580 TI - Convection-induced stabilization of optical dissipative solitons. AB - In spatially extended convective systems, the reflection symmetry breaking induced by drift effects leads to a striking nonlinear effect that drastically affects the formation and stability of dissipative solitons in optical parametric oscillators. The phenomenon of nonlinear-induced convection dynamics is revealed using a model of the complex quintic Ginzburg-Landau equation with nonlinear gradient terms in it. Mechanisms leading to stabilization of dissipative solitons by convection are singled out. The predictions are in very good agreement with numerical solutions found from the governing equations of the optical parametric oscillators. PMID- 22089581 TI - Optimizing diffraction catastrophe evaluation. AB - A theoretical analysis is proposed, aimed at investigating the character of those power series expansions recently considered for the evaluation of several types of diffraction catastrophes. A hyperlinear convergence is found to be the signature for such expansions, so that the results of the numerical experiments recently carried out find a meaningful interpretation in terms of the accelerating action operated by the Weniger transformation. As an important by product of our analysis, simple criteria, aimed at numerically optimizing the diffraction catastrophe evaluations, are provided through analytical expressions. PMID- 22089582 TI - Integrated optical temporal Fourier transformer based on a chirped Bragg grating waveguide. AB - We experimentally demonstrate the first integrated temporal Fourier transformer based on a linearly chirped Bragg grating waveguide written in silica glass with a femtosecond laser. The operation is based on mapping the energy spectrum of the input optical signal to the output temporal waveform by making use of first-order chromatic dispersion. The device operates in reflection, has a bandwidth of 10 nm, and can be used for incident temporal waveforms as long as 20 ps. Experimental results, obtained through both temporal oscilloscope traces and Fourier transform spectral interferometry, display a successful Fourier transformation of in-phase and out-of-phase pairs of input optical pulses, and demonstrate the correct functionality of the device for both amplitude and phase of the temporal output. PMID- 22089583 TI - High-numerical-aperture microlens shape measurement with digital holographic microscopy. AB - In this Letter, we introduce an algorithm that overcomes limitations in shape measurement by holographic microscopic methods in cases of micro-optical elements with high NA, such as microlenses. The presented algorithm provides a simple method for shape reconstruction from interferometrically measured phase. The algorithm is based on the analysis of local ray transition through the measured object. We develop algorithms for holographic configurations working in transmission and reflection. The accuracy of the developed algorithms is proved by experiments and extensive simulations. We present an experiment in a holographic Mach-Zehnder configuration where we have measured and successfully reconstructed the height distribution of spherical and cylindrical microlenses with NA up to 0.3. PMID- 22089584 TI - Optimal pulse compression in long hollow fibers. AB - The spectral broadening performance of 1 m and 3 m long hollow fibers are compared. The 3 m capillary clearly outperforms the 1 m one in terms of both transmission and achievable spectral broadening. Starting from 1.1 mJ 71 fs pulses at 780 nm, a spectral broadening ratio of 26 was achieved using a single 3 m long argon-filled hollow fiber. After compression the measured pulse duration was 4.5 fs corresponding to a compression ratio of 16 at an energy of 0.42 mJ. Both the pulse duration and the pulse energy were limited by the applied chirped mirrors. PMID- 22089585 TI - Diode-pumped mode-locked Yb:YCOB laser generating 35 fs pulses. AB - Direct sub-50-fs pulse generation is demonstrated with a mode-locked Yb:YCa4O(BO3)3 laser. With external compression, pulses as short as 35 fs are generated at 1055 nm. The oscillator operating at a repetition rate of 95 MHz is pumped by a two-section distributed Bragg reflector tapered diode laser and mode locked by a semiconductor saturable absorber mirror. The onset of self-Raman conversion for pulse spectral bandwidths exceeding 40 nm (FWHM) is observed. PMID- 22089586 TI - Detecting shadows from a single image. AB - We present a novel (to our best knowledge) optical recognition technique for detecting shadows from a single image. Most prior approaches definitely depend on explicit physical computational models, but physics-based approaches have the critical problem that they may fail severely even with slight perturbations. Unlike traditional approaches, our method does not rely on any explicit physical models. This breakthrough originates from a discovery of a new modeling mechanism, derived from a biological vision principle, the so-called retinex theory, which is well suited for single-image shadow detection. Experimental results demonstrate that the proposed method outperforms the previous optical recognition techniques and gives robust results even in real-world complex scenes. PMID- 22089587 TI - Superior optical limiting, stabilization, and spatio-temporal reshaping of ultrashort laser pulses in an opto-stable intrinsic polymer film. AB - A chemically modified poly(fluorene-alt-benzothiadiazole) (PFBT) polymer film is reported to exhibit high two-photon absorbing capability and chemical/physical stability upon the action of high-power laser pulses of ~780 nm wavelength and ~160 fs duration. A nonlinear transmission measurement is conducted by varying the input intensity from ~20 to ~600 GW/cm2, the corresponding nonlinear transmission of a ~70 MUm thick film is reduced from ~0.8 to 0.18, indicating a superior optical limiting behavior. In the meantime, intensity fluctuation of laser pulses can be significantly reduced after passing through the same film sample. Based on the intensity-dependent nonlinear attenuation mechanism, a straightforward optical reshaping effect on spatio-temporal profiles of the laser pulses has also been demonstrated. PMID- 22089588 TI - Electromagnetically induced transparency-like transmission in periodically poled lithium niobate with a defect. AB - Electromagnetically induced transparency (EIT)-like transmission is observed in an electro-optic (EO) tunable periodically poled lithium niobate (PPLN) with a central defect. When an electric field is applied, light satisfying the phase matching condition keeps its original polarization, although it experiences polarization rotation then turns back. Therefore the corresponding light always may pass though freely but with an EO tunable phase and dispersion. On the other hand, light with a neighboring wavelength is blocked. An EIT-like spectrum is thus obtained with tunable group delay. A low-voltage bulk phase shifter with over two orders of magnitude larger index change is obtained. PMID- 22089589 TI - Optical Doppler shift with structured light. AB - When a light beam with a transverse spatially varying phase is considered for optical remote sensing, in addition to the usual longitudinal Doppler frequency shift of the returned signal induced by the motion of the scatter along the beam axis, a new transversal Doppler shift appears associated to the motion of the scatterer in the plane perpendicular to the beam axis. We discuss here how this new effect can be used to enhance the current capabilities of optical measurement systems, adding the capacity to detect more complex movements of scatters. PMID- 22089590 TI - Microwave photonic quadrature filter based on an all-optical programmable Hilbert transformer. AB - A microwave photonic quadrature filter, new to our knowledge, based on an all optical Hilbert transformer is presented. It is based on mapping of a Hilbert transform transfer function between the optical and electrical domains, using a programmable Fourier-domain optical processor and high-speed photodiodes. The technique enables the realization of an extremely wide operating bandwidth, tunable programmable bandwidth, and a highly precise amplitude and phase response. Experimental results demonstrate a microwave quadrature filter from 10 to 20 GHz, which achieves an amplitude imbalance of less than +/-0.23 dB and a phase imbalance of less than +/-0.5 degrees . PMID- 22089591 TI - Sub-100-as timing jitter optical pulse trains from mode-locked Er-fiber lasers. AB - We demonstrate sub-100-as timing jitter optical pulse trains generated from free running, 77.6 MHz repetition-rate, mode-locked Er-fiber lasers. At -0.002(+/ 0.001) ps2 net cavity dispersion, the rms timing jitter is 70 as (224 as) integrated from 10 kHz (1 kHz) to 38.8 MHz offset frequency, when measured by a 24 as resolution balanced optical cross correlator. To our knowledge, this result corresponds to the lowest rms timing jitter measured from any mode-locked fiber lasers so far. The measured result also agrees fairly well with the Namiki-Haus analytic model of quantum-limited timing jitter in stretched-pulse fiber lasers. PMID- 22089592 TI - Negative Goos-Hanchen shift in periodic media. AB - We show that, under certain conditions, a negative Goos-Hanchen shift-a longitudinal displacement of a totally internally reflected wave packet-occurs in periodic media such as waveguide arrays. PMID- 22089593 TI - Extreme events in the Ti:sapphire laser. AB - We report experimental and theoretical evidence of the existence of extreme value events in the form of scarce and randomly emerging giant pulses in the femtosecond (self-pulsing or Kerr-lens mode-locked) Ti:sapphire laser. This laser displays complex dynamical behavior, including deterministic chaos, in two different regimes. The extreme value pulses are observed in the chaotic state of only one of these two regimes. The observations agree with the predictions of a well-tested theoretical model that does not include noise or self-Q-switching into its framework. This implies that, in this laser, the extreme effects have a nontrivial dynamical origin. The Ti:sapphire laser is hence revealed as a new and convenient system for the study of these effects. PMID- 22089594 TI - Paraxial and nonparaxial polynomial beams and the analytic approach to propagation. AB - We construct solutions of the paraxial and Helmholtz equations that are polynomials in their spatial variables. These are derived explicitly by using the angular spectrum method and generating functions. Paraxial polynomials have the form of homogeneous Hermite and Laguerre polynomials in Cartesian and cylindrical coordinates, respectively, analogous to heat polynomials for the diffusion equation. Nonparaxial polynomials are found by substituting monomials in the propagation variable z with reverse Bessel polynomials. These explicit analytic forms give insight into the mathematical structure of paraxially and nonparaxially propagating beams, especially in regard to the divergence of nonparaxial analogs to familiar paraxial beams. PMID- 22089595 TI - Experimental demonstration of coherent beam combining over a 7 km propagation path. AB - We demonstrate coherent combining (phase locking) of seven laser beams emerging from an adaptive fiber-collimator array over a 7 km atmospheric propagation path using a target-in-the-loop (TIL) setting. Adaptive control of the piston and the tip and tilt wavefront phase at each fiber-collimator subaperture resulted in automatic focusing of the combined beam onto an unresolved retroreflector target (corner cube) with precompensation of quasi-static and atmospheric turbulence induced phase aberrations. Both phase locking (piston) and tip-tilt control were performed by maximizing the target-return optical power using iterative stochastic parallel gradient descent (SPGD) techniques. The performance of TIL coherent beam combining and atmospheric mitigation was significantly increased by using an SPGD control variation that accounts for the round-trip propagation delay (delayed SPGD). PMID- 22089596 TI - Ultrashort pulse characterization with a terahertz streak camera. AB - A phase-locked terahertz transient is exploited as an ultrafast phase gate for femtosecond optical pulses. We directly map out the group delay dispersion of a low-power near-infrared pulse by measuring the electro-optically induced polarization rotation as a function of wavelength. Our experiment covers the spectral window from 1.0 to 1.4 MUm and reaches a temporal precision better than 1 fs. A quantitative analysis of the detector response confirms that this streaking technique requires no reconstruction algorithm and is also well suited for the characterization of pulses spanning more than one optical octave. PMID- 22089597 TI - Zonal slope prediction for open-loop adaptive optics. AB - We present what we believe to be the first results that obtained with the recursive least square zonal slope predictor working on an open-loop liquid crystal adaptive optics system operating on astronomical implementation at visible and near infrared wavelength on a 1.23 m telescope. The system produces substantially better results than a direct open-loop correction based on previous measurement. A 27% relative gain in full-width at half-maximum and 30% relative gain in Strehl ratio are obtained. PMID- 22089598 TI - Derivatives of light scattering properties of a nonspherical particle computed with the T-matrix method. AB - Based on the T-matrix formalism, we analytically calculate derivatives of light scattering quantities by a nonspherical particle with respect to its microphysical parameters. Illustrative computations are performed for a spheroid, and the results agree with those obtained by finite differencing. The proposed formalism also predicts correctly derivatives for a sphere obtained by linearized Lorenz-Mie theory. PMID- 22089599 TI - The great push for mental health: why it matters for India. PMID- 22089600 TI - Vitamin B12 deficiency & cognitive impairment in elderly population. PMID- 22089601 TI - Endpoints in advanced breast cancer: methodological aspects & clinical implications. AB - Breast cancer is an increasingly important public health problem in developing countries, with disproportionately high mortality. The increasing availability of active agents against advanced breast cancer makes the development of novel treatments and their choice in clinical practice progressively more complex. Furthermore, there is often a tension between the adequacy of endpoints used in clinical trials and the clinician's aim of improving survival and quality of life, the two most important therapeutic goals in advanced breast cancer. However, overall survival (OS) is no longer a suitable indicator of treatment efficacy within clinical trials in settings for which effective subsequent-line therapy exists. Conversely, progression-free survival (PFS) currently represents the most sensitive parameter to assess the efficacy of a new drug or combination in such settings. When coupled with a favourable toxicity profile and cost, the demonstration of an improved PFS may be enough evidence for the superiority of a treatment. Despite arguments favouring the use of PFS as a primary endpoint in clinical trials, clinicians who need to make sense of the available literature may be reluctant to use PFS as an indicator of clinical benefit when deciding among different therapeutic strategies for their patients. This choice is further complicated if one fails to distinguish between the use of an efficacy parameter as an indicator of therapeutic objective for individual patients and as a clinical trial endpoint. This brief review aims at helping clinicians in their daily need to interpret the literature and make informed treatment choices for patients with advanced breast cancer. PMID- 22089602 TI - An insight into the drug resistance profile & mechanism of drug resistance in Neisseria gonorrhoeae. AB - Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post quinolone era. Among the antimicrobials available so far, only the third generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea. PMID- 22089603 TI - Vitamin B12 deficiency & levels of metabolites in an apparently normal urban south Indian elderly population. AB - BACKGROUND & OBJECTIVES: There is no published literature on the extent of vitamin B12 deficiency in elderly Indians as determined by plasma vitamin B12 levels and methylmalonic acid (MMA) levels. Vitamin B12 deficiency is expected to be higher in elderly Indians due to vegetarianism, varied socio-economic strata and high prevalence of Helicobacter pylori infection. We therefore, studied the dietary habits of south Indian urban elderly population and measured vitamin B12, MMA red cell folate and homocysteine (Hcy) levels. METHODS: Healthy elderly urban subjects (175, >60 yr) were recruited. Detailed history, physical examination and neurological assessment were carried out. Food Frequency Questionnaire (FFQ) for dietary analysis for daily intake of calories, vitamin B12, folate and detailed psychological assessment for cognitive functions was carried out. Blood samples were analyzed for routine haematology and biochemistry, vitamin B12, red cell folate, MMA and Hcy. RESULTS: The mean age of the study population was 66.3 yr. Median values for daily dietary intake of vitamin B12 and folate were 2.4 and 349.2 MUg/day respectively. Sixty two (35%) participants consumed multivitamin supplements. Plasma vitamin B12 level and the dietary intake of vitamin B12 was significantly correlated (P=0.157). Plasma vitamin B12 and Hcy were inversely correlated (P= -0.509). Red cell folate was inversely correlated with Hcy (P= 0.550). Significant negative correlation was observed between plasma vitamin B12 and MMA in the entire study population (P= -0.220). Subjects consuming vitamin supplements (n=62) had significantly higher plasma vitamin B12 levels, lower MMA levels and lower Hcy levels. There was no significant correlation between plasma vitamin B12, MMA, Hcy and red cell folate and any of the 10 cognitive tests including Hindi Mental Status Examination (HMSE). INTERPRETATION & CONCLUSIONS: Our study is indicative of higher vitamin B12 (2.4 MUg/day) intakes in urban south Indian population. Thirty five per cent of the study population consumed multivitamin supplements and therefore, low plasma vitamin B12 levels were seen only in 16 per cent of the study subjects. However, MMA was elevated in 55 per cent and Hcy in 13 per cent of the subjects. PMID- 22089604 TI - Prevalence & correlates of primary infertility among young women in Mysore, India. AB - BACKGROUND & OBJECTIVES: There are sparse data on the prevalence of primary infertility in India and almost none from Southern India. This study describes the correlates and prevalence of primary infertility among young women in Mysore, India. METHODS: The baseline data were collected between November 2005 through March 2006, among 897 sexually active women, aged 15-30 yr, for a study investigating the relationship of bacterial vaginosis and acquisition of herpes simplex virus type-2 (HSV-2) infection. A secondary data analysis of the baseline data was undertaken. Primary infertility was defined as having been married for longer than two years, not using contraception and without a child. Logistic regression was used to examine factors associated with primary infertility. RESULTS: The mean age of the women was 25.9 yr (range: 16-30 yr) and the prevalence of primary infertility was 12.6 per cent [95% Confidence Interval (CI): 10.5-15.0%]. The main factor associated with primary infertility was HSV-2 seropositivity (adjusted odds ratio: 3.41; CI: 1.86, 6.26). INTERPRETATION & CONCLUSIONS: The estimated prevalence of primary infertility among women in the study was within the range reported by the WHO and similar to other estimates from India. Further research is needed to examine the role of HSV-2 in primary infertility. PMID- 22089605 TI - Identifying potential pitfalls in interpreting mitochondrial DNA mutations of male infertility cases. AB - BACKGROUND & OBJECTIVES: Recently, a significantly higher ratio of nucleotide changes in the mtDNA genes: COII, ATPase 6, ATPase 8, ND2, ND3, ND4, and ND5 was reported in spermatozoa from populations of infertile Indian men, compared suggesting that screening for mtDNA mutations could provide insight into the aetiology of male infertility. In this study, we examined the published data and found serious errors in the original acquisition and analysis of the data. METHODS: The mtDNA data associated with male infertility in Indian populations were retrieved from the published sources. The mtDNA substitution values of infertile and control groups were evaluated using phylogenetic methods and previously published mtDNA phylogenies. RESULTS: Most of the mtDNA polymorphisms reported as significantly correlated with infertility were more commonly found in general populations. Further, our analysis showed that some of the mtDNA substitutions were erroneously overestimated in the infertile groups and underestimated in the control groups, and vice-versa. INTERPRETATION & CONCLUSIONS: Contrary to earlier claims, our analysis demonstrated no significant association between the mtDNA polymorphisms and male infertility in these studies. Further, these errors in the published data impune the usefulness of mitochondrial molecular analyses in male infertility diagnosis. PMID- 22089606 TI - Cytogenetic profile of Indian patients with de novo myelodysplastic syndromes. AB - BACKGROUND & OBJECTIVES: Myelodysplastic syndrome (MDS) is a clonal haematopoietic stem cell disorder characterized by ineffective haematopoiesis and leukaemia progression. Cytogenetic analysis has proven to be a mandatory part of the diagnosis of MDS as well as a major indicator for predicting clinical course and outcome. Studies on cytogenetics of MDS are reported mostly from the West and only a few are available from Asian countries. We report herein cytogenetic studies on 40 Indian patients with primary MDS to find out the occurrence and type of chromosome abnormalities and recurring defects. METHODS: Cytogenetic analysis was done using GTG banding and karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN). RESULTS: Of the 40 patients, 19 patients (47.5%) showed clonal karyotypic abnormalities with distribution as follows: 3 of 15 (20%) of refractory anaemia (RA), 4 of 7 (57%) of refractory anaemia with excess blasts-1 (RAEB-1), 4 of 6 (67%) of refractory anaemia with excess blasts 2 (RAEB-2), 2 of 3 (67%) of refractory anaemia with ring sideroblasts (RARS), 2 of 4 (50%) of refractory cytopenia with multilineage dysplasia (RCMD), none (0%) RCMD-ringed sideroblasts (RCMD-RS) and 4 patients with 5q syndrome. The frequent abnormalities observed in our study were -7, 5q and trisomy 8. INTERPRETATION & CONCLUSIONS: Two rare chromosomal abnormalities (6q-, 3q-) were found with unknown prognostic significance. Hence, cytogenetic analysis may be incorporated in the routine diagnosis of MDS since there are racial differences in clinical pictures and the molecular events. PMID- 22089607 TI - A pilot study on the use of serum glyoxalase as a supplemental biomarker to predict malignant cases of the prostate in the PSA range of 4-20 ng/ml. AB - BACKGROUND & OBJECTIVES: Serum prostate specific antigen (PSA) though most commonly used for diagnosis of prostate cancer lacks specificity. This study was aimed at exploring the use of serum glyoxalase as a supplemental biomarker to differentiate between malignant vs non-malignant diseases of the prostate in patients with PSA in the range of 4-20 ng/ml. METHODS: Serum glyoxalase and PSA were measured in 92 men (30 control, 31 cases of benign prostate hyperplasia (BPH) and 31 cases of adenocarcinoma of prostate). Of the latter group, 11 cases of prostate cancer in the PSA range of 4-20 ng/ml were included for studying the diagnostic utility of combination of both serum PSA and glyoxalase. RESULTS: In prostate cancer cases with PSA in the range of 4-20 ng/ml, the glyoxalase was found to be 233.3 +/- 98.6 MUmol/min while for the non-malignant group it was 103.1 +/- 19.7 MUmol/min. A cut-off of 19.2 ng/ml PSA showed sensitivity of 9 per cent, specificity of 96.7 per cent, positive predictive value (PPV) of 50 per cent and negative predictive value (NPV) of 75 per cent. A serum glyoxalase cut off of 141 MUmol/min showed sensitivity of 81.8 per cent, specificity of 100 per cent, PPV of 100 per cent and NPV of 93.9 per cent. Further, ROC analysis showed a significant difference in the area under curve (AUC) for glyoxalase as compared to serum PSA (0.92 vs 0.57; P<0.001). INTERPRETATION & CONCLUSIONS: Serum glyoxalase appears to be predictive of prostate cancer in the PSA range of 4-20 ng/ml. Studies with larger number of participants would be required to confirm this finding. PMID- 22089608 TI - Cardiovascular autonomic functions & cerebral autoregulation in patients with orthostatic hypotension. AB - BACKGROUND & OBJECTIVES: Patients of orthostatic hypotension may or may not have symptoms of the cerebral hypoperfusion despite fall in the blood pressure. The present study was done to quantify autonomic functions and cerebral autoregulation in patients of orthostatic hypotension with or without symptoms. METHODS: The study was conducted in 15 patients of orthostatic hypotension and 15 age, sex matched control subjects. The sympathetic reactivity was measured by diastolic blood pressure response to handgrip test (DeltaDBP in HGT) and cold pressor test (DeltaDBP in CPT). The parasympathetic reactivity was measured by E:I ratio during deep breathing test (DBT) and Valsalva ratio (VR) during Valsalva maneuver. The cerebral autoregulation was computed from the changes in the cerebral blood flow, cerebrovascular conductance and blood pressure measured during different time points during head-up tilt (HUT). RESULTS: The sympathetic reactivity was lower in patients as compared to controls [DeltaDBP in HGT: 10 (4 16) vs 18 (12 - 22) mmHg, P<0.01; DeltaDBP in CPT : 10 (4-12) vs 16 (10-20) mmHg, P<0.01]. The parasympathetic reactivity was also lower in patients as compared to controls. The sympathetic and parasympathetic reactivity was comparable in the symptomatic and asymptomatic patients. The maximum fall in blood pressure during HUT was comparable between symptomatic and asymptomatic patients (29.14 +/- 10.94 vs 29.50 +/- 6.39 mmHg), however, the percentage fall in the cerebral blood flow was significantly higher in the symptomatic (P<0.05) compared to asymptomatics. INTERPRETATION & CONCLUSIONS: Patients with orthostatic hypotension had deficits in sympathetic and parasympathetic control of cardiovascular system. Cerebral autoregulation was present in asymptomatic patients (increase in cerebrovascular conductance) during HUT while it was lost in symptomatic patients. PMID- 22089609 TI - Prevalence of & knowledge, attitude & practices towards HIV & sexually transmitted infections (STIs) among female sex workers (FSWs) in Andhra Pradesh. AB - BACKGROUND & OBJECTIVES: As part of the baseline survey carried out during 2005 06, biological and behavioural data were generated on about 3200 female sex workers (FSWs), from eight districts of Andhra Pradesh (AP), India. This study describes the relationship between socio-demographic and behavioural factors with consistent condom use (CCU) and HIV among FSWs in AP. METHODS: A cross-sectional community-based study was conducted among female sex workers (FSW) in eight districts of Andhra Pradesh, India, using conventional cluster sampling and time location cluster sampling. Key risk behaviours and STIs related to the spread of HIV were assessed. Blood samples were collected to detect syphilis, Herpes simplex virus type 2 (HSV-2) Chlamydia trachomatis (CT), Neiserria gonorrhoeae (NG) and HIV serology. RESULTS: About 70 per cent of the FSWs were illiterates, nearly 50 per cent were currently married and 41 per cent of the FSWs had sex work as the sole source of income. More than 95 per cent of the FSWs heard of HIV, but about 99 per cent believed that HIV/AIDS cannot be prevented. Logistic regression analysis showed significantly lesser CCU with high client volume, not carrying condom and could not use condom in past 1 month due to various reasons such as non co-operation by the clients. Similarly, CCU was significantly (P<0.001) lesser (only 8.9%) with regular non-commercial partners. Overall there was 16.3 per cent prevalence of HIV amongst FSWs. C. trachomatis and N. gonorrheae were prevalent in 3.4 and 2 per cent of the FSWs, respectively and about 70 per cent of the FSWs were positive for HSV2 serology. HIV was significantly associated with STIs. INTERPRETATION & CONCLUSIONS: Misconception that HIV/AIDS cannot be prevented is very high. Most of the subjects in the present study had first sexual debut at a very young age. HIV was associated with STIs, emphasizing aggressive STI diagnosis and treatment. CCU must be emphasized right from first sexual debut with all clients and non-commercial partners as well. PMID- 22089610 TI - Enhanced production of mosquitocidal cyclic lipopeptide from Bacillus subtilis subsp. subtilis. AB - BACKGROUND & OBJECTIVES: A cyclic lipopeptide, surfactin produced by a strain of Bacillus subtilis subsp. subtilis (VCRC B471) was found to exhibit activity against both the larval and pupal stages of mosquitoes. The present study was aimed at increasing the production of the mosquitocidal metabolite by modifying the conventional medium. METHODS: Enhancement of mosquitocidal metabolite production was attempted by replacing the existing micronutrients of the conventional NYSM and supplementing the medium with additional amounts of glucose. The LC50 value of culture supernatant (CS) against the larval and pupal stages of Anopheles stephensi was determined. Crude mosquitocidal metabolite (CMM) was separated from the CS, identified by MALDI-TOF analysis and its LC50 dosage requirement for the pupal stage of the above mosquito species determined. RESULTS: The medium containing a new composition of micronutrients and glucose up to 1 per cent resulted in increased metabolite production. The LC50 value of the CS obtained in the improved medium against larvae and pupae of An. stephensi was 5.57 and 0.71 MUl/ml, respectively. The yield of CMM was doubled in the improved medium. MALDI-TOF analysis revealed that the CMM was surfactin. INTERPRETATION & CONCLUSIONS: The new improved medium enhanced the production of mosquitocidal metabolite as the dosage required for inciting 50 per cent mortality among the pupal stages of mosquitoes was only half of that required when the metabolite was produced in the conventional medium. The mosquitocidal metabolite was identified as surfactin, a cyclic lipopeptide and biosurfactant. PMID- 22089611 TI - ATR-X syndrome in two siblings with a novel mutation (c.6718C>T mutation in exon 31). AB - ATR-X syndrome is an X-linked mental retardation syndrome characterized by mental retardation, alpha thalassaemia and distinct facial features which include microcephaly, frontal hair upsweep, epicanthic folds, small triangular nose, midface hypoplasia and carp-shaped mouth. Here we report two brothers with clinical features of ATR-X syndrome, in whom a novel missense (C>T) mutation was identified in exon 31 of the ATRX gene. PMID- 22089612 TI - CTX-M15 type ESBL producing Salmonella from a paediatric patient in Chennai, India. PMID- 22089613 TI - The inherited disorders of haemoglobin: an increasingly neglected global health burden. AB - An estimated 300,000 babies are born each year with a severe inherited disease of haemoglobin and that over 80 per cent of these births occur in low- or middle income countries. As these countries go through the epidemiological transition, characterized by a reduction in childhood and infant mortality due to improved public health measures, infants who had previously died of these conditions before they were recognised are now surviving to present for diagnosis and treatment. For a variety of reasons, even in the rich countries there are limited data about the true frequency, natural history, and survival of patients with these disorders, information that is absolutely critical towards providing governments and international health agencies with accurate information about the true global health burden of these conditions. The situation can only be improved by major action on the part of the rich countries together with the formation of partnerships between rich and poor countries and input from the major international health agencies and funding organisations. PMID- 22089614 TI - Haemoglobinopathies in southeast Asia. AB - In Southeast Asia alpha-thalassaemia, beta-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. The abnormal genes in different combinations lead to over 60 different thalassaemia syndromes, making Southeast Asia the locality with the most complex thalassaemia genotypes. The four major thalassaemic diseases are Hb Bart's hydrops fetalis (homozygous alpha thalassaemia 1), homozygous beta-thalassaemia, beta-thalassaemia/Hb E and Hb H diseases. alpha-Thalassaemia, most often, occurs from gene deletions whereas point mutations and small deletions or insertions in the beta-globin gene sequence are the major molecular defects responsible for most beta-thalassaemias. Clinical manifestations of alpha-thalassaemia range from asymptomatic cases with normal findings to the totally lethal Hb Bart's hydrops fetalis syndrome. Homozygosity of beta-thalassaemia results in a severe thalassaemic disease while the patients with compound heterozygosity, beta-thalassaemia/Hb E, present variable severity of anaemia, and some can be as severe as homozygous beta thalassaemia. Concomitant inheritance of alpha-thalassaemia and increased production of Hb F are responsible for mild clinical phenotypes in some patients. However, there are still some unknown factors that can modulate disease severity in both alpha- and beta-thalassaemias. Therefore, it is possible to set a strategy for prevention and control of thalassaemia, which includes population screening for heterozygotes, genetic counselling and foetal diagnosis with selective abortion of affected pregnancies. PMID- 22089615 TI - Past, present & future scenario of thalassaemic care & control in India. AB - The first case of thalassaemia, described in a non-Mediterranean person, was from India. Subsequently, cases of thalassaemia were documented in all parts of India. Centres for care of thalassaemics were started in the mid-1970s in Mumbai and Delhi, and then in other cities. The parent's associations, with the help of International Thalassemia Federation, greatly helped in improving the care of thalassaemics. Obtaining blood for transfusion was difficult, but the Indian Red Cross Society and the parent's associations played a crucial role in arranging voluntary donations of blood. Chelation with deferoxamine was used sparingly due to the high cost. The Indian physicians conducted trials with deferiprone, and the drug was first approved and marketed in India. Deferasirox is also now being administered. Studies of physical and pubertal growth documented significant retardation, suggesting that generally patients receive inadequate chelation and transfusions. Bone marrow transplantation is available at a number of centres, and cord blood stem cell storage facilities have been established. Information about mutations in different parts of India is available, and ThalInd, an Indian database has been set up. There is a need to set up preimplantation genetic diagnosis and non-invasive prenatal diagnosis. It is argued that too much emphasis should not be placed on premarital screening. The focus should be on screening pregnant women to yield immediate results in reducing the burden of this disorder. Care of thalassaemia has been included in the 12 th 5-year Plan of the Government of India. Many States now provide blood transfusions and chelation free of cost. Although inadequacies in care of thalassaemia remain, but the outlook is bright, and the stage is set for initiating a control programme in the high risk States. PMID- 22089616 TI - Hb E/beta-thalassaemia: a common & clinically diverse disorder. AB - Haemoglobin E-beta thalassaemia (Hb E/beta-thalassaemia) is the genotype responsible for approximately one-half of all severe beta-thalassaemia worldwide. The disorder is characterized by marked clinical variability, ranging from a mild and asymptomatic anaemia to a life-threatening disorder requiring transfusions from infancy. The phenotypic variability of Hb E/beta-thalassaemia and the paucity of long-term clinical data, present challenges in providing definitive recommendations for the optimal management of patients. Genetic factors influencing the severity of this disorder include the type of beta-thalassaemia mutation, the co-inheritance of alpha-thalassaemia, and polymorphisms associated with increased production of foetal haemoglobin. Other factors, including a variable increase in serum erythropoietin in response to anaemia, previous or ongoing infection with malaria, previous splenectomy and other environmental influences, may be involved. The remarkable variation, and the instability, of the clinical phenotype of Hb E beta-thalassaemia suggests that careful tailoring of treatment is required for each patient, and that therapeutic approaches should be re-assessed over-time. PMID- 22089617 TI - Pathophysiological insights in sickle cell disease. AB - The first coherent pathophysiological scheme for sickle cell disease (SCD) emerged in the sixties-seventies based on an extremely detailed description of the molecular mechanism by which HbS in its deoxy-form polymerises and forms long fibres within the red blood cell that deform it and make it fragile. This scheme explains the haemolytic anaemia, and the mechanistic aspects of the vaso occlusive crises (VOCs), but, even though it constitutes the basic mechanism of the disease, it does not account for the processes that actually trigger VOCs. This paper reviews recent data which imply: red blood cell dehydration, its abnormal adhesion properties to the endothelium, the participation of inflammatory phenomenon and of a global activation of all the cells present in the vessel, and finally, abnormalities of the vascular tone and of nitric oxide metabolism. These data altogether have shed a new light on the pathophysiology of the first molecular disease i.e. sickle cell disease. PMID- 22089618 TI - Abnormal haemoglobins: detection & characterization. AB - Haemoglobin (Hb) abnormalities though quite frequent, are generally detected in populations during surveys and programmes run for prevention of Hb disorders. Several methods are now available for detection of Hb abnormalities. In this review, the following are discussed: (i) the methods used for characterization of haemoglobin disorders; (ii) the problems linked to diagnosis of thalassaemic trait; (iii) the strategy for detection of common Hb variants; and (iv) the difficulties in identification of rare variants. The differences between developing and industrialized countries for the strategies employed in the diagnosis of abnormal haemoglobins are considered. We mention the limits and pitfalls for each approach and the necessity to characterize the abnormalities using at least two different methods. The recommended strategy is to use a combination of cation-exchange high performance chromatography (CE-HPLC), capillary electrophoresis (CE) and when possible isoelectric focusing (IEF). Difficult cases may demand further investigations requiring specialized protein and/or molecular biology techniques. PMID- 22089619 TI - Ethical issues in genetic counselling with special reference to haemoglobinopathies. AB - Genetic counselling is provided in places where genetic tests are carried out. The process involves pre-test counselling as well as post-test counselling to enable the individuals to face the situation and take appropriate decisions with the right frame of mind. Major ethical principles which govern the attitudes and actions of counsellors include: respect for patient autonomy, non-maleficence, beneficence, or taking action to help benefit others and prevent harm, both physical and mental, and justice, which requires that services be distributed fairly to those in need. Other moral issues include veracity, the duty to disclose information or to be truthful, and respect for patient confidentiality. Nondirective counselling, a hallmark of this profession, is in accordance with the principle of individual autonomy. High prevalence of haemoglobinopathies with availability of good and sensitive carrier detection tests and prenatal diagnostic techniques makes these good candidates for population screening of carriers along with genetic counselling for primary prevention of the disease. Screening of the extended family members of the affected child, high risk communities and general population screening including antenatal women are the main target groups for planning a Haemoglobinopathy control programme. A critical mass of trained genetic counsellors who have understanding of the ethical issues and its appropriate handling with the required sensitivity is needed in India. PMID- 22089620 TI - Invasive & non-invasive approaches for prenatal diagnosis of haemoglobinopathies: experiences from India. AB - The thalassaemias and sickle cell disease are the commonest monogenic disorders in India. There are an estimated 7500 - 12,000 babies with beta-thalassaemia major born every year in the country. While the overall prevalence of carriers in different States varies from 1.5 to 4 per cent, recent work has shown considerable variations in frequencies even within States. Thus, micromapping would help to determine the true burden of the disease. Although screening in antenatal clinics is being done at many centres, only 15-20 per cent of pregnant women register in antenatal clinics in public hospitals in the first trimester of pregnancy. There are only a handful of centres in major cities in this vast country where prenatal diagnosis is done. There is considerable molecular heterogeneity with 64 mutations identified, of which 6 to 7 common mutations account for 80-90 per cent of mutant alleles. First trimester foetal diagnosis is done by chorionic villus sampling (CVS) and DNA analysis using reverse dot blot hybridization, amplification refractory mutation system (ARMS) and DNA sequencing. Second trimester diagnosis is done by cordocentesis and foetal blood analysis on HPLC at a few centres. Our experience on prenatal diagnosis of haemoglobinopathies in 2221 pregnancies has shown that >90 per cent of couples were referred for prenatal diagnosis of beta-thalassaemia after having one or more affected children while about 35 per cent of couples were referred for prenatal diagnosis of sickle cell disorders prospectively. There is a clear need for more data from India on non-invasive approaches for prenatal diagnosis. PMID- 22089621 TI - Genetic counselling in tribals in India. AB - Genetic counselling in tribals unlike general population residing in cities and near villages is a difficult task due of their lower literacy and poor socio economic status. However, sustained effort is essential with a close interaction in the local language, certain misbeliefs need to be removed gradually taking into account their socio-cultural background. The present communication deals with our experience in counselling for haemoglobinopathies during Neonatal Screening Programme undertaken for sickle cell disease in Kalahandi district of Orissa and Community Screening Programmes in primitive tribes of India in four States viz. Orissa, Gujarat, Tamil Nadu and Maharashtra. Counselling during neonatal screening programme was very well accepted demonstrating the benefit to the small babies as regards the morbidity. Premarital marriage counselling was also accepted by them. The success rate as followed up for 5 years is almost 50 per cent, the limitation being long follow up. Genetic counselling in these areas has to be continuous to achieve success and therefore the need for setting up of permanent centres in the tribal areas in India. PMID- 22089622 TI - Haemoglobinopathies in Greece: prevention programme over the past 35 years. AB - At present, prevention of thalassaemia and sickle cell disease is the only realistic approach to control the birth of new patients in countries having high numbers of carriers. This is fully justified because avoiding the birth of an ever increasing number of patients may allow a more effective use of the available resources in improving the management of the patients surviving today and alleviate the already overloaded public health system from the inevitable tremendous and ever increasing cost. Moreover, prenatal diagnosis may help couples at risk to have non-thalassaemic children. Greece is one of the countries where the mean frequency of carriers is approximately 7.5 per cent (population 11 million) and has set up a nationwide programme for carrier identification in the early seventies; this is provided through a dozen of specific Units attached to the major Blood Transfusion Services of the country, on a voluntary basis and free of charge. Spread of information through mass media, the schools, and other groups has greatly contributed in creating the necessary sensitization; obstetricians and antenatal Clinics are also instrumental to this effect. Prenatal diagnosis is offered centrally (Athens) and covers satisfactorily the estimated needs (500-600 annually); the total number has already exceeded 35,000. According to information obtained from the major paediatric hospitals all over the country, the number of thalassaemia major or SCD admitted for treatment over the last ten years has been around 15 yearly (instead of an estimate of 120-130). PMID- 22089623 TI - Water quality of selected fluvial lakes in the context of the Elbe River pollution and anthropogenic activities in the floodplain. AB - The paper evaluates the status of selected fluvial lakes situated in the central part of the Elbe River and the impact of anthropogenic activities including comparison with the Elbe River water quality on them. To achieve the goals of the project, eight researched lakes differed from each other in the intensity of communication with the river, morphometric parameters and in the possibility of anthropogenic contamination (industrial, agricultural and municipal) were chosen. Besides observing the hydrological regime, the research was focused on physical and chemical parameters of water. To sum up, the lakes communicating above ground with the river showed similarities in several parameters, e.g. organic load or conductivity was nearly at the same level, which was lower than in the separated ones. Although the values of nitrates were higher in the river, their content did not reach such concentrations even in the connected lakes because of their more stagnant character. In general, although the Elbe River has a significant effect on water quality of researched lakes, especially in the case of lakes with a restricted communication with the river, their water quality is a result of local conditions, e.g. possibility of contamination by sewage waters, land use in the vicinity, etc. PMID- 22089624 TI - Pollution levels of thiobencarb, propanil, and pretilachlor in rice fields of the muda irrigation scheme, Kedah, Malaysia. AB - The purpose of this study was to investigate the potential risk of pretilachlor, thiobencarb, and propanil pollutants in the water system of the rice fields of the Muda area. The study included two areas that used different irrigation systems namely non-recycled (N-RCL) and recycled (RCL) water. Regular water sampling was carried out at the drainage canals during the weeding period from September to October 2006 in the main season of 2006/2007 and April-May 2007 in off season of 2007. The herbicides were extracted by the solid-phase extraction method and identified using a GC-ECD. Results showed that the procedure for identification of the three herbicides was acceptable based on the recovery test values, which ranged from 84.1% to 96.9%. A wide distribution pattern where more than 79% of the water samples contained the herbicide pollutants was observed at both the areas where N-RCL and RCL water was supplied for the two seasons. During September to October 2006, high weedicide residue concentration was observed at the N-RCL area and it ranged from 0.05 to 1.00 MUg/L for pretilachlor and propanil and 10-25 MUg/L for thiobencarb. In the case of the area with RCL water, the weedicide residue ranged from 1 to 5 MUg/L for pretilachlor and propanil and 10-25 MUg/L for thiobencarb. The highest residue level reached was 25-50, 50-100, and 100-200 MUg/L for pretilachlor, propanil, and thiobencarb, respectively. During April to May 2007, high residue concentration frequently occurred at the area supplied with N-RCL irrigation water and it ranged from 0.05 to 1.00, 10 to 25, and 25 to 50 MUg/L for pretilachlor, propanil, and thiobencarb, respectively. The highest residue level reached was 25-50 MUg/L for pretilachlor and 100-200 MUg/L for propanil and thiobencarb. There was an accelerated increase in the concentration of the herbicide residues, with the maximum levels reached at the early period of weedicide application, followed by a sharp decrease after the rice fields were completely covered with the rice crop. During the main season of 2006/2007, the concentration of propanil residue gradually rose, although that of the other herbicides declined. PMID- 22089625 TI - Bioindicative comparison of the fern Athyrium distentifolium for trace pollution in the Sudety and Tatra mountains of Poland. AB - Concentrations of the elements Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were measured in the fronds of the fern Athyrium distentifolium from the Sudety and Tatra mountains (Poland). The A. distentifolium sites in the Sudety mountains which were influenced by long-range metal transport from the former Black Triangle were distinguished by the principal component and classification analysis (PCCA). These sites were situated on the west side slopes of one of the ranges in the Sudety mountains (within a 150-km radius of the heart of the former Black Triangle) at an altitude of 700 m asl, and exposed to prevailing winds. This most affected area had significantly higher foliar concentrations of Cu, Cr and Ni which are typical for long-range transported airborne elements occurring in coal fly ash emitted by lignite combustion industry. PMID- 22089626 TI - Statistical evaluation of data from multi-laboratory testing of a measurement method intended to indicate the presence of dust resulting from the collapse of the World Trade Center. AB - In this paper we describe a statistical analysis of the inter-laboratory data summarized in Rosati et al. (2008) to assess the performance of an analytical method to detect the presence of dust from the collapse of the World Trade Center (WTC) on September 11, 2001. The focus of the inter-lab study was the measurement of the concentration of slag wool fibers in dust which was considered to be an indicator of WTC dust. Eight labs were provided with two blinded samples each of three batches of dust that varied in slag wool concentration. Analysis of the data revealed that three of labs, which did not meet measurement quality objectives set forth prior to the experimental work, were statistically distinguishable from the five labs that did meet the quality objectives. The five labs, as a group, demonstrated better measurement capability although their ability to distinguish between the batches was somewhat mixed. This work provides important insights for the planning and implementation of future studies involving examination of dust samples for physical contaminants. This work demonstrates (a) the importance of controlling the amount of dust analyzed, (b) the need to take additional replicates to improve count estimates, and (c) the need to address issues related to the execution of the analytical methodology to ensure all labs meet the measurement quality objectives. PMID- 22089627 TI - Field application of SPME as a novel tool for occupational exposure assessment with inhalational anesthetics. AB - Occupational exposure to inhalational anesthetics occurs routinely in operating rooms. It could induce serious health hazards and diseases. This exposure assessment is a crucial step in determining risks. In this study, a pen-shaped holder for solid-phase microextraction (SPME) sampler was successfully applied as a time-weighted average sampling tool for workshift exposure assessment of operation room staff to halothane. It proved to be very convenient for use in occupational environments such as operation rooms. Samples were analyzed by a gas chromatography-mass spectrometry. The validity of the SPME method was checked in real-world conditions with Occupational Safety and Health Administration (OSHA) 103 standard method for the determination of inhalational anesthetics. A good agreement between OSHA 103 and SPME methods was obtained and results demonstrated no statistically significant differences in anesthetic concentrations determined by the two analytical methods (p >= 0.05). It is concluded that SPME in retracted mode could successfully be applied in occupational exposure assessment purposes. PMID- 22089628 TI - Nucleobase recognition at alkaline pH and apparent pKa of single DNA bases immobilised within a biological nanopore. AB - The four DNA bases are recognized in immobilized DNA strands at high alkaline pH by nanopore current recordings. Ionic currents through the biological nanopores are also employed to measure the apparent pK(a) values of single nucleobases within the immobilised DNA strands. PMID- 22089629 TI - Effects of oxidative stress on vascular function, and the role of anesthetics. PMID- 22089630 TI - Successful treatment of severe asthma-associated plastic bronchitis with extracorporeal membrane oxygenation. AB - We describe a case of near-fatal asthma requiring extracorporeal membrane oxygenation (ECMO). The patient presented with severe respiratory distress, which was not responsive to conventional pharmacological therapy. The patient also failed to respond to mechanical ventilation and thus was placed on venovenous ECMO for temporary pulmonary support. A fiberoptic bronchoscopy revealed that large amounts of thick bronchial secretions had occluded the main bronchus, which suggested plastic bronchitis secondary to asthma. Aggressive airway hygiene with frequent bronchoscopies and application of biphasic cuirass ventilation for facilitation of secretion clearance were performed to improve the patient's respiratory status. The patient achieved a full recovery and suffered no neurological sequelae. This case illustrates that aggressive pulmonary hygiene with ECMO is a useful therapy for patients with asthma-associated plastic bronchitis. PMID- 22089631 TI - Pandemic influenza H1N1: reconciling serosurvey data with estimates of the reproduction number. AB - BACKGROUND: During the 2009 pandemic of influenza A (H1N1), many studies reported estimates of the reproduction number from outbreak data. Since then, seroprevalence studies have been conducted in a number of countries to assess the proportion of the population that was infected in the first wave of the pandemic. METHODS: Here, we collate the reproduction number estimates, and use mathematical models to reconcile these with serosurvey data. RESULTS: Most estimates of the reproduction number from outbreaks are in the range of 1.0-2.0, whereas mean estimates calculated from seroprevalence data range from 1.14 to 1.36. Age specific analysis of these data suggests that the reproduction number for children was approximately 1.6, whereas the reproduction numbers for adults >25 years of age was less than 1.0. CONCLUSION: The difference between age-groups may help to explain high estimates of the reproduction number from outbreaks involving a large proportion of child cases. PMID- 22089632 TI - Identity statuses as developmental trajectories: a five-wave longitudinal study in early-to-middle and middle-to-late adolescents. AB - This study tested whether Marcia's original identity statuses of achievement, moratorium, early closure (a new label for foreclosure), and diffusion, can be considered identity status trajectories. That is, we examined whether these statuses are distinct and relatively stable, over-time configurations of commitment strength, levels of in-depth exploration of present commitments, and consideration of alternative commitments. The study examined identity development in a five-wave study of 923 early-to-middle (49.3% female) and 390 middle-to-late adolescents (56.7% female), covering the ages of 12-20. Using Latent class growth analysis (LCGA), the authors found that Marcia's (1966) statuses are indeed identity status trajectories. Two kinds of moratorium were also found: the classical moratorium and searching moratorium. Support was found for Waterman's developmental hypothesis of the identity status model: the number of achievers was significantly higher, and the number of diffusions lower, in middle-to-late adolescence than in early-to-middle adolescence. Females were more often in the advanced identity status trajectories, and stable differences were found between the trajectories in psychosocial adjustment. Study findings highlight that identity formation should be conceptualized as an over-time process. PMID- 22089633 TI - Perceived ethnic stigma across the transition to college. AB - Ethnicity-based negative treatment during the transition to college may affect the long-term adjustment of ethnic-minority youth. We examined within-person changes in youths' perceptions of overt discrimination and their sense of their ethnic group being devalued by the larger society among 563 Latino, European, Asian, and other ethnic minority emerging adults across the transition to college (M (age) = 17.79, SD = .37, 54.7% female). Analyses tested for group and context differences and associations between perceived discrimination and societal devaluation of their group and adjustment. Results indicate that although perceived discrimination decreases over time, perceived devaluation by society increases. Social context did not affect changes in perceived discrimination and societal devaluation. Whereas perceived discrimination was associated with depressive and somatic symptoms for everyone, perceived societal devaluation was only consequential for ethnic minorities. Future research should identify possible moderators to help students cope with experiences of discrimination and feelings of not being valued by society. PMID- 22089634 TI - Metal-mediated DNA assembly using the ethynyl linked terpyridine ligand. AB - The terpyridine ligand directly attached to the 5-position of a uridine allows metal-mediated DNA assembly towards potentially electronically coupled DNA conjugates. PMID- 22089635 TI - The influence of depression on the progression of HIV: direct and indirect effects. AB - The authors suggest a theoretical model of pathways of HIV progression, with a focus on the contributions of depression-as well as secondary, behavioral and emotional variables. Literature was reviewed regarding (a) comorbid depression and the direct physiological effects on HIV progression and (b) intermediary factors between HIV and disease progression. Intermediary factors included (a) substance use, (b) social support, (c) hopelessness, (d) medication nonadherence, and (e) risky sexual behavior and the contraction of secondary infections. The authors suggest direct physiological pathways from depression to HIV progression and indirect pathways (e.g., behavioral, social, and psychological). In addition to depression, substance use, poor social support, hopelessness, medication nonadherence, and risky sexual behavior seem to be integral in HIV progression. Based on the individual relationships of these variables to depression and HIV progression, a comprehensive multipath model, incorporating all factors, serves to explain how severe emotional distress may lead to accelerated progression to AIDS. PMID- 22089636 TI - Role of the amino-terminal transmembrane domain of sulfonylurea receptor SUR2B for coupling to K(IR)6.2, ligand binding, and oligomerization. AB - ATP-sensitive K(+) (K(ATP)) channels consist of two types of subunits, K(IR)6.x that form the pore, and sulfonylurea receptors (SURs) that serve as regulatory subunits. SURs are ATP-binding cassette (ABC) proteins and contain, in addition to two nucleotide binding folds, the binding sites for channel openers such as diazoxide and P1075 and channel inhibitors such as glibenclamide (GBC) and repaglinide. Structurally, SURs differ from most eukaryotic ABC proteins by an additional amino-terminal transmembrane domain (TMD0); in case of SUR1, the subunit of the pancreatic K(ATP) channel, TMD0 serves as a major domain for association with K(IR). In this study we sought to elucidate the roles of TMD0 in SUR2B, the smooth muscle gating subunit, in the coupling between SUR2B and K(IR)6.2, in the self-association of SUR2B and in channel modulator binding to SUR2B. SUR2B has a weaker affinity for sulfonylureas thus SUR2B(Y1206S), with a higher affinity for GBC, but an equivalent opener binding was used. Association of SUR2B(YS)Delta, lacking TMD0, with K(IR)6.2 was shown by immunoprecipitation; however, no evidence for formation of functional channels was obtained. SUR2B(YS)Delta self-associates like SUR2B(YS) and binds GBC, repaglinide, and P1075 with slightly reduced affinities. The binding profile of the SUR2B(YS)Delta/K(IR)6.2 complex differs slightly but significantly from that of SUR2B(YS)Delta alone showing impaired allosteric coupling of binding sites. We conclude that TMD0 is not required for oligomerization of SUR2B, is of only minor importance in ligand binding, but is essential for both functional and allosteric coupling of SUR2B to K(IR)6.2. PMID- 22089637 TI - Mitochondria in motor nerve terminals: function in health and in mutant superoxide dismutase 1 mouse models of familial ALS. AB - Mitochondria contribute to neuronal function not only via their ability to generate ATP, but also via their ability to buffer large Ca(2+) loads. This review summarizes evidence that mitochondrial Ca(2+) sequestration is especially important for sustaining the function of vertebrate motor nerve terminals during repetitive stimulation. Motor terminal mitochondria can sequester large amounts of Ca(2+) because they have mechanisms for limiting both the mitochondrial depolarization and the increase in matrix free [Ca(2+)] associated with Ca(2+) influx. In mice expressing mutations of human superoxide dismutase -1 (SOD1) that cause some cases of familial amyotrophic lateral sclerosis (fALS), motor terminals degenerate well before the death of motor neuron cell bodies. This review presents evidence for early and progressive mitochondrial dysfunction in motor terminals of mutant SOD1 mice (G93A, G85R). This dysfunction would impair mitochondrial ability to sequester stimulation-associated Ca(2+) loads, and thus likely contributes to the early degeneration of motor terminals. PMID- 22089638 TI - Cerebrospinal fluid cytokine dynamics differ between Alzheimer disease patients and elderly controls. AB - The time courses of levels of multiple plasma and cerebrospinal fluid (CSF) cytokines in patients with Alzheimer disease (AD) and in age-matched control subjects were compared. Interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, IL 12p70, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor alpha levels were measured 7 times over a 24-hour period in plasma and CSF using a lumbar catheter. Baseline plasma and CSF cytokine levels were found to be similar in AD and control subjects. However, the CSF levels of all measured cytokines, except IL-6 and IL-8, diverged over time between AD and control subjects, such that CSF cytokine levels in AD subjects were higher than in controls. This difference was greatest at 24 hours after the insertion of the lumbar catheter. In contrast, no differences in cytokine trajectories were seen in plasma. These data suggest that the neuroinflammatory response to lumbar catheter placement differs between AD and control subjects. PMID- 22089640 TI - neuroRAD--idea and realization of a new concept. PMID- 22089639 TI - Historical changes in the severity of dementia and accompanying neuropsychiatric symptoms in persons presenting for evaluation in a multiracial urban dementia center. AB - OBJECTIVE: We examine historical changes from 1992 to 2008 in the severity of dementia and accompanying neuropsychiatric symptoms among persons presenting for evaluation and treatment at a multiracial urban dementia center. METHODS: We reviewed intakes of white (n=197) and black (n=568) patients seen at a dementia center in New York City. Intakes were divided into 3 time categories: period 1 (1992 to 1996), period 2 (1997 to 2002), and period 3 (2003 to 2008). Diagnoses included the following: Alzheimer disease (73%), vascular dementia (13%), mixed dementia (9%), mild cognitive impairment (2%), and other dementias (4%). RESULTS: Over the 3 assessment periods, persons increasingly presented at an earlier stage of illness with significantly higher levels of cognition and functioning, and a declining prevalence of psychotic symptoms and agitation. Blacks had a more advanced stage of illness, lower cognitive scores, and a greater prevalence of psychotic symptoms than whites in period 1, but not during the other time periods. There were no racial differences in functioning, agitation, or depression. CONCLUSION: Over the period 1992 to 2008, patients were increasingly more likely to present with early stages of dementia and fewer symptoms of psychoses and agitation, and racial differences in illness severity and neuropsychiatric symptoms disappeared. If our sample reflects trends in the United States, then it suggests that more persons will be in care for longer periods of time, previous research findings derived from dementia centers must be considered historically specific, and clinicians must be prepared to work with persons with milder forms of neurocognitive disorders. PMID- 22089641 TI - Unusual spectral renormalization in hexaborides. AB - Employing high resolution photoemission spectroscopy, we studied the evolution of the spectral features in rare earth hexaboride single crystals as a function of temperature and 4f binding energy, where the variation of the 4f binding energy is obtained by changing the rare earth element. High energy resolution helped to reveal the distinct features corresponding to the various photoemission final states. Experimental results of CeB(6), a dense Kondo system, exhibit the growth of the features near the Fermi level with the decrease in temperature relative to the uncompensated local moment contributions. The valence band spectra of the antiferromagnetic compounds, PrB(6) and NdB(6), exhibit multiple features-the 4f ionization peaks (poorly screened features) appear at higher binding energies and the features in the vicinity of the Fermi level possessing significant 4f character are due to the well-screened photoemission final states. These results indicate finite hybridization between the 4f and B 2s2p conduction electronic states. Interestingly, the well-screened features in PrB(6) and NdB(6) exhibit unusual enhancement in intensity at low temperature. PMID- 22089642 TI - Functional analysis of APOE locus genetic variation implicates regional enhancers in the regulation of both TOMM40 and APOE. AB - Genetic variation within the apolipoprotein E gene (APOE) locus is associated with late-onset Alzheimer's disease risk and quantitative traits as well as apoE expression in multiple tissues. The aim of this investigation was to explore the influence of APOE locus cis-regulatory element enhancer region genetic variation on regional gene promoter activity. Luciferase reporter constructs containing haplotypes of APOE locus gene promoters; APOE, APOC1 and TOMM40, and regional putative enhancers; TOMM40 intervening sequence (IVS)2-4, TOMM40 IVS6 poly-T, as well as previously described enhancers; multienhancer 1 (ME1), or brain control region (BCR), were evaluated for their effects on luciferase activity in three human cell lines. Results of this investigation demonstrate that in SHSY5Y cells, the APOE promoter is significantly influenced by the TOMM40 IVS2-4 and ME1, and the TOMM40 promoter is significantly influenced by the TOMM40 IVS6 poly-T, ME1 and BCR. In HepG2 cells, theTOMM40 promoter is significantly influenced by all four enhancers, whereas the APOE promoter is not influenced by any of the enhancers. The main novel finding of this investigation was that multiple APOE locus cis-elements influence both APOE and TOMM40 promoter activity according to haplotype and cell type, suggesting that a complex transcriptional regulatory structure modulates regional gene expression. PMID- 22089643 TI - Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma. AB - Analysis of the microRNA (miRNA) expression signature of lung squamous cell carcinoma (lung-SCC) revealed that the expression levels of miR-133a were significantly reduced in cancer tissues compared with normal tissues. In this study, we focused on the functional significance of miR-133a in cancer cell lines derived from lung-SCC and the identification of miR-133a-regulated novel cancer networks in lung-SCC. Restoration of miR-133a expression in PC10 and H157 cell lines resulted in significant inhibition of cell proliferation, suggesting that miR-133a functions as a tumor suppressor. We used genome-wide gene expression analysis to identify the molecular targets of miR-133a regulation. Gene expression data and web-based searching revealed several candidate genes, including transgelin 2 (TAGLN2), actin-related protein2/3 complex, subunit 5, 16kDa (ARPC5), LAG1 homolog, ceramide synthase 2 (LASS2) and glutathione S transferase pi 1 (GSTP1). ARPC5 and GSTP1 likely represent bona fide targets as their expression is elevated in lung-SCC clinical specimens. Furthermore, transient transfection of miR-133a, repressed ARPC5 and GSTP1 mRNA and protein levels. As cell proliferation was significantly inhibited in lung-SCC cells following RNAi knock down of either gene, ARPC5 and GSTP1 may function as oncogenes in the development of lung-SCC. The identification of a tumor suppressive miRNA and the novel cancer pathways it regulates could provide new insights into potential molecular mechanisms of lung-SCC carcinogenesis. PMID- 22089644 TI - Molecular and biochemical characterization of Tunisian patients with glycogen storage disease type III. AB - Glycogen storage disease type III (GSD III) is an autosomal recessive inborn error of metabolism caused by mutations in the glycogen debranching enzyme amylo 1,6-glucosidase gene, which is located on chromosome 1p21.2. GSD III is characterized by the storage of structurally abnormal glycogen, termed limit dextrin, in both skeletal and cardiac muscle and/or liver, with great variability in resultant organ dysfunction. The spectrum of AGL gene mutations in GSD III patients depends on ethnic group. The most prevalent mutations have been reported in the North African Jewish population and in an isolate such as the Faroe Islands. Here, we present the molecular and biochemical analyses of 22 Tunisian GSD III patients. Molecular analysis revealed three novel mutations: nonsense (Tyr1148X) and two deletions (3033_3036del AATT and 3216_3217del GA) and five known mutations: three nonsense (R864X, W1327X and W255X), a missense (R524H) and an acceptor splice-site mutation (IVS32-12A>G). Each mutation is associated to a specific haplotype. This is the first report of screening for mutations of AGL gene in the Tunisian population. PMID- 22089645 TI - Single-level anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cage and allograft bone. AB - BACKGROUND: In an effort to avoid the morbidity associated with autogenous bone graft harvesting, cervical cages in combination with allograft bone are used to achieve fusion. The goal of the current study was to assess the reliability and efficacy of anterior cervical discectomy and interbody fusion (ACDF) using a PEEK anatomical cervical cage in the treatment of patients affected by single-level cervical degenerative disease. METHODS AND MATERIALS: Twenty-five patients affected by single-level cervical degenerative pathology between C4 and C7 were enrolled in this study. The clinical findings were assessed using the Neck Disability Index and the Visual Analog Scale. Surgical outcomes were rated according to Odom's criteria at last follow-up. Fusion was graded as poor, average, good or excellent by assessing the radiographs. Cervical spine alignment was evaluated by sagittal segmental alignment and sagittal alignment of the whole cervical spine preoperatively, 6 months postoperatively and at the last follow up. RESULTS: Twenty-five patients underwent ACDF using a PEEK anatomical cervical cage. All patients had a minimum 2 years of follow-up. The operative levels were C4-C5 in 5 patients, C5-C6 in 12 patients and C6-C7 in 8 patients. Preoperatively, average NDI was 34, 13 at 6 months, and 10 at latest follow-up. The mean preoperative VAS was 7; the mean postoperative VAS at latest follow-up was 3. Good or excellent fusion was achieved in all patients within 10 months (mean 5 months). Preoperatively, average sagittal segmental alignment (SSA) was 0.2 degrees and average sagittal alignment of the cervical spine (SACS) 15.8 degrees . Six months after surgery, average SSA was 1.8 degrees and average SACS 20.9 degrees , and at last follow-up, average SSA was 1.6 degrees and average SACS 18.5 degrees . CONCLUSION: Anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cages can be considered a safe and effective technique to cure cervical disc herniation with intractable pain or neural deficit in cases where conservative treatment failed. PMID- 22089646 TI - POCIS sampling in combination with ELISA: screening of sulfonamide residues in surface and waste waters. AB - Sulfonamide antibiotics coming from both human and veterinary medicine are among the most common emerging pollutants in freshwater. The present paper shows the successful application of passive sampling using POCIS in combination with an immunochemical ELISA technique and HPLC/MS/MS analysis to study the distribution of sulfonamides in streams around small towns in the Czech Republic, as well as around a major agglomeration of the city of Brno, including its waste water treatment plant (WWTP). Results indicated the presence of sulfonamides at most studied sites with concentrations ranging from <20 up to 736 ng of sulfamethoxazole equivalents per POCIS. Very high levels were detected in both the influent and effluent of the Brno WWTP with maxima > 8000 ng SMX per POCIS. All samplers collected down-stream of the studied towns and WWTPs clearly showed an increase in sulfonamide drug residues. Higher concentrations were determined in rivers at the city of Brno agglomeration. In agreement with other available studies, these findings indicate low efficiency of conventional WWTPs to eliminate polar pharmaceuticals such as sulfonamides. Good performance and correlation with the LC/MS results, as well as ease of use, indicate good potential for the immunochemical ELISA technique to become the screening tool for sulfonamide determination in surface waters including passive samplers. PMID- 22089647 TI - A putative neuronal network controlling the activity of the leg motoneurons of the stick insect. AB - It is widely accepted that the electrical activity of motoneurons that drive locomotion in the stick insect are controlled by two separate mechanisms: (i) the frequency of the activity through the central pattern generator, which provides the rhythm of movement during locomotion and (ii) the 'magnitude' through circuits distinct from the earlier one. In this study, we show a possible way of how this control mechanism might be implemented in the nervous system of the stick insect by means of a network model. To do this, we had to define the 'magnitude' of the neuronal activity more precisely as the average number of spikes per unit time. The model was constructed on the basis of relevant electrophysiological and morphological data. However, only their integration in the model led to the novel properties that enable the network quickly to adapt the motoneuronal activity to central commands or sensory signals by changing both the firing pattern and intensity of the motoneuron discharges. The network would thus act as the controlling network for each of the muscle pairs that move the individual joints in each of the legs. Our model may contribute to a better understanding of the mechanisms that underlie the fast adaptive control of locomotion in this, and possibly in other types of locomotor systems. PMID- 22089648 TI - Role of Broca's area in motor sequence programming: a cTBS study. AB - Besides language, the contribution of Broca's area to motor cognition is now widely accepted. In this study, we investigated the role of its posterior part (left Brodmann area 44) in learning of a motor sequence by altering its functioning with a continuous theta-burst transcranial magnetic stimulation (cTBS) in 12 healthy participants before they learned the sequence by observation. Twelve control individuals underwent the same experiment with cTBS applied over the vertex. Although cTBS over Brodmann area 44 did not impair sequence learning, it significantly increased the response latency as measured during the retention test, performed 24 h later. This finding suggests that Broca's area might be critically involved in organizing, and/or storing, the individual components of a motor sequence before its execution. PMID- 22089649 TI - Taiwanese fathers' experiences of having their child diagnosed with a developmental disability. AB - BACKGROUND: Receiving a diagnosis of a developmental disability in a child can be a crisis event for parents. Gender differences in parental roles are worth considering when exploring the impact of having a child with a disability. However, most studies on this topic have focused on the mother's experience, and little is known about what the father goes through as the parent of a child diagnosed with a disability. Even less is known regarding this experience in the context of the Chinese culture. PURPOSE: The goal of this study was to explore fathers' experiences of having a child diagnosed with a developmental disability in a Chinese cultural context. METHODS: This study used a hermeneutic phenomenological approach informed by the philosophical world views of Heidegger. The 16 fathers who participated in the study were purposively sampled from a teaching hospital in central Taiwan. Data were collected using in-depth and semistructured interviews and were analyzed using hermeneutic analysis. RESULTS: Data analysis revealed four shared meanings: losing hope, feelings of failure, being frustrated with family conflicts, and searching for positive coping strategies. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Fathers feel shock and despair as well as personally devalued when learning that their child has been diagnosed with a developmental disability. Chinese cultural beliefs and values can elicit different experiences for fathers while helping them make sense of their experiences and accept their child in meaningful ways. Nurses can actively engage fathers as well as mothers to understand their feelings and thoughts about their child's disability to provide appropriate emotional and informational support. Providing support or referral is necessary particularly when fathers encounter issues with the child's grandparents. Nurses can assist fathers to find a way to make sense of having a child with a disability within their cultural frame of reference by adapting cultural beliefs and values to their situation and to make meaning of their child's life. PMID- 22089650 TI - Exploration of clinical nurses' perceptions of spirituality and spiritual care. AB - BACKGROUND: Florence Nightingale emphasized the need for nurses to honor the psychological and spiritual aspects of patients to promote patients' health. Whereas study of a public hospital in Singapore presented similar findings, few studies have explored clinical nurses' perceptions of spirituality. PURPOSE: The purpose of this study was to investigate the role of specific nurse demographic characteristics in predicting perception differences with regard to spirituality and spiritual care. METHODS: The Chinese version of the Spirituality and Spiritual Care Rating Scale was developed using a translate and back-translate process, achieving a content validity index of .98. This study used a cross sectional descriptive survey with 350 clinical nurses as the study sample. Three hundred forty-nine valid questionnaires were returned (response rate, 99.71%). The institutional review board of the hospital approved this study. RESULTS: Most participants were women, ranging in age from 23 to 64 years. Participants' clinical experience ranged from less than 1 year to 40 years, with a mean experience value of 13.42 years. Participants were distributed among all clinical specialties. Slightly less than half (41.83%) professed no religious belief, and most were not involved in religious activities (55.01%, n = 192). A little over half (53.58%, n = 187) had received spiritual care lessons during nurse training, and more than half (58.74%, n = 205) had received spiritual care continuous education after graduation. This survey found perception of spirituality positively related to holding a master's degree, 11 to 19 years of clinical experience, specialty in palliative nursing, and having received spiritual care lessons during nursing training or continuing education. Clinical nurses who held a master's degree or received spiritual care lessons during continuing education had higher levels of spiritual care perception. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study found education to have a positive impact on participants' perception of spirituality and spiritual care. A higher education level and more spiritual care lessons or training courses were found to increase perception level. Study findings provide preliminary insights into nurses' perceptions of spirituality and spiritual care in Taiwan. Findings demonstrate an urgent need for additional education programs or training in spiritual care to improve the ability of nurses in catering to the spiritual needs of patients and guide clinical nurses when conducting spiritual care. PMID- 22089651 TI - Effectiveness of a self-care program in improving symptom distress and quality of life in congestive heart failure patients: a preliminary study. AB - BACKGROUND: Prevalence of heart failure is increasing among older adults. Most heart failure patients experience distressing symptoms that lead to decreased physical functioning, poor quality of life, and a high incidence of rehospitalization. Health education about heart failure self-care (HFSC) is very important during hospitalization for these patients. However, lack of ongoing follow-up after discharge makes evaluation and disease management difficult. This is a significant problem in Taiwan. PURPOSE: This study was undertaken to determine if participants with heart failure who were managed under the HFSC program had fewer distressing symptoms, better functional status, improved quality of life, and reduced hospital and emergency readmission rates compared with control group participants. METHODS: This study used a quasi-experimental design with a control group that received usual care and an intervention group that received usual care plus the HFSC program. Twenty-seven participants were recruited from 2 cardiac general wards at 1 medical center in Taipei City, Taiwan, and were randomized into intervention (n = 14) and control (n = 13) groups. RESULTS: : After 3 months, there were significant differences in symptom distress (p < .01), 6-minute walk test results (p < .01), and quality of life (using Short Form 36, Taiwan version, p < .05) between the HFSC and control groups but no significant differences in hospital readmission and emergency department visits. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The HFSC program for patients with heart failure improved their heart failure symptoms and resulted in increased functional status and better quality of life. HFSC is a workable program in the clinical environment. Advanced nurse practitioners can use HFSC methods and principles to provide improved education and follow-up to heart failure patients. PMID- 22089652 TI - The effects of low-impact dance on knee torque and lower extremity mobility in middle-aged and older women. AB - BACKGROUND: Although low-impact dance is one of the most prevalent exercises in older persons, little is known about its effects on knee torque and range of motion (ROM) in lower extremity joints. PURPOSE: The aim of this study was to examine the effects of low-impact dance on knee torque and lower extremity joint ROM in older women. METHODS: Twenty-six low-impact dancers and 12 physically inactive individuals comprised the dance group (DG) and the control group (CG), respectively. The knee extension torque, knee and ankle ROMs, and bone mineral density in calcanei were measured for all participants. RESULTS: Several ROMs of the lower extremity joints in the dominant leg, ankle inversion, plantarflexion, and dorsiflexion were significantly higher in the DG than in the CG (p < .05). In addition, the ankle inversion of the nondominant leg in the DG was also significantly higher than that in the CG. The knee extension torque of the nondominant leg in the DG was significantly higher than that in the CG (p < .05). CONCLUSION: Although this study did not focus on the efficacy of a particular intervention type, the results showed that low-impact dance can help achieve higher lower extremity ROM and knee torque values than attained by inactive individuals. It is hoped that this exposition of positive benefits will encourage further studies related to the effect of low-impact dance intervention on reducing fall risk. PMID- 22089653 TI - A systematic review of sleep patterns and factors that disturb sleep after heart surgery. AB - BACKGROUND: Sleep is a vital and restorative human function. However, it has been reported that up to 50% of heart surgery patients experience sleep disturbance during hospitalization and after discharge. PURPOSE: This study describes sleep patterns in adults over the recovery course after heart surgery and works to identify potential interventions. Researchers analyzed and synthesized studies of sleep patterns and sleep-related factors in heart surgery patients. METHODS: Observational studies describing sleep through the course of recovery from heart surgery were searched from databases of PubMed, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Current Contents, and Chinese Electronic Periodicals Service from 1966 to 2011. Only studies that used polysomnography, actigraphy, or self-report sleep questionnaires to measure sleep were recruited in this review. Results of sleep patterns and sleep quality were pooled from homogeneity studies. RESULTS: Eight studies that investigated sleep patterns in heart surgery patient and nine studies that examined factors associated with sleep disturbances in this patient group were analyzed and synthesized. Serious problems including low sleep efficiency and difficulty in maintaining sleep often happened during the first postoperative week. It took 2 months for sleep to recover to preoperational levels. Although sleep quality improved over time, sleep disturbances still persisted through 6 months of recovery. Physical factors, including pain, dyspnea, nocturia, and cardiac function, and environmental factors, including noise, light, and procedures on patients, were associated with sleep disturbances during hospitalization. Psychological factors, including anxiety and depression, affected sleep during the first -6 months after discharge. Individual factors of age and gender affected sleep through the entire recovery course. CONCLUSIONS/IMPLICATION FOR PRACTICE: Sleep disturbances persist over the course of recovery in heart surgery patients, and sleep disturbance is associated with individual, physiological, psychological, and environmental factors. Findings suggest that management of major symptoms and control of the patient's sleeping environment during hospitalization and at early recovery stage as well as mental healthcare after discharge may improve sleep quality and recovery in heart surgery patients. PMID- 22089654 TI - Brushing teeth with purified water to reduce ventilator-associated pneumonia. AB - BACKGROUND: Oral care may decrease the development of ventilator-associated pneumonia (VAP) and improve oral hygiene. However, little evidence is available to guide the development of oral care protocols. The practical effect of toothbrushing on VAP development and oral health and hygiene improvement is inconclusive. PURPOSE: This study evaluated the effects in postneurosurgical, intensive care unit patients of brushing teeth twice daily with purified water on VAP rates and oral health or hygiene. METHODS: This study conducted a randomized controlled pilot trial. Patients consecutively admitted to the surgical intensive care unit at a suburban hospital in 2007 were invited to participate if they met two inclusion criteria: (a) under ventilator support for at least 48 to 72 hours and (b) no current pneumonia. Upon obtaining informed consent, subjects were randomized into experimental and control groups. Both groups received usual hospital care, that is, daily oral care using cotton swabs. The experimental group additionally received a twice-daily oral care protocol of toothbrushing with purified water, elevating the head of the bed, and before-and-after hypopharyngeal suctioning. The control group also received twice-daily mock oral care (elevating the head of the bed, moisturizing the lips, and before-and-after hypopharyngeal suctioning). VAP was defined by a clinical pulmonary infection score of > 6. Oral hygiene and health was assessed after conclusion of the intervention. RESULTS: Patients (N = 53) were predominantly male (64.2%), mean age was 60.6 years old, and most had received emergency surgery (75.5%). After 7 days of toothbrushing with purified water, cumulative VAP rates were significantly lower in the experimental (17%) than in the control (71%; p <.05) group. The experimental group also had significantly better scores for oral health (p <.05) and plaque index (p <.01). CONCLUSION/IMPLICATION FOR PRACTICE: Findings suggest that, as an inexpensive alternative to existing protocols, toothbrushing twice daily with purified water reduces VAP and improves oral health and hygiene. PMID- 22089655 TI - Relationship between elderly depression and health status in male veterans. AB - BACKGROUND: Elderly depression affects the overall health and quality of life of institutionalized men. PURPOSE: This study explored the relationship between depression and health status in institutionalized male veterans in Taiwan. METHODS: This survey study used a cross-sectional research design and recruited 152 elderly male residents of a veterans' home in northern Taiwan. A validated questionnaire assessed depression, health status, and demographic characteristics. RESULTS: More than one fifth of the subjects (21.7%) exhibited depression. Those with poor general health status (odds ratio [OR] = 7.9, p < .001), relatively high levels of dependence on others for daily physical activities (OR = 4.6, p = .002), or self-perceived negative influences of chronic diseases on daily living (OR = 11.7, p < .001) faced the highest prevalence of depression. Subjects with hypertension (OR = 2.3, p = .034), cataracts (OR = 3.7, p = .007), or liver disease (OR = 8.1, p = .006) had the highest prevalence of depression. Identified risk factors of depression among the elderly male veterans included self-perceived negative influence of chronic diseases on daily living (adjusted OR = 10.2, p < .001) and cataracts (adjusted OR = 4.3, p = .023). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Geriatrician nurses should develop strategies to maintain general patient health and reduce the negative impact of chronic diseases and cataracts on daily life to reduce depression in institutionalized male veterans. PMID- 22089656 TI - A computer literacy scale for newly enrolled nursing college students: development and validation. AB - BACKGROUND: Increasing application and use of information systems and mobile technologies in the healthcare industry require increasing nurse competency in computer use. Computer literacy is defined as basic computer skills, whereas computer competency is defined as the computer skills necessary to accomplish job tasks. Inadequate attention has been paid to computer literacy and computer competency scale validity. PURPOSE: This study developed a computer literacy scale with good reliability and validity and investigated the current computer literacy of newly enrolled students to develop computer courses appropriate to students' skill levels and needs. METHODS: This study referenced Hinkin's process to develop a computer literacy scale. Participants were newly enrolled first-year undergraduate students, with nursing or nursing-related backgrounds, currently attending a course entitled Information Literacy and Internet Applications. Researchers examined reliability and validity using confirmatory factor analysis. RESULTS: The final version of the developed computer literacy scale included six constructs (software, hardware, multimedia, networks, information ethics, and information security) and 22 measurement items. Confirmatory factor analysis showed that the scale possessed good content validity, reliability, convergent validity, and discriminant validity. This study also found that participants earned the highest scores for the network domain and the lowest score for the hardware domain. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: With increasing use of information technology applications, courses related to hardware topic should be increased to improve nurse problem-solving abilities. This study recommends that emphases on word processing and network-related topics may be reduced in favor of an increased emphasis on database, statistical software, hospital information systems, and information ethics. PMID- 22089657 TI - Modeling the final phase of landfill gas generation from long-term observations. AB - For waste management, methane emissions from landfills and their effect on climate change are of serious concern. Current models for biogas generation that focus on the economic use of the landfill gas are usually based on first order chemical reactions (exponential decay), underestimating the long-term emissions of landfills. The presented study concentrated on the curve fitting and the quantification of the gas generation during the final degradation phase under optimal anaerobic conditions. For this purpose the long-term gas generation (240 1,830 days) of different mechanically biologically treated (MBT) waste materials was measured. In this study the late gas generation was modeled by a log-normal distribution curve to gather the maximum gas generation potential. According to the log-normal model the observed gas sum curve leads to higher values than commonly used exponential decay models. The prediction of the final phase of landfill gas generation by a fitting model provides a basis for CO(2) balances in waste management and some information to which extent landfills serve as carbon sink. PMID- 22089658 TI - Methamphetamine exposure and chronic illness in police officers: significant improvement with sauna-based detoxification therapy. AB - BACKGROUND: The medical literature reports health hazards for law enforcement personnel from repeated exposure to methamphetamine and related chemical compounds. Most effects appear transitory, but some Utah police officers with employment-related methamphetamine exposures developed chronic symptoms, some leading to disability. This report is of an uncontrolled retrospective medical chart evaluation of symptomatic officers treated with a sauna detoxification protocol designed to reduce the chronic symptoms and improve the quality of life. METHODS: Sixty-nine officers consecutively entering the Utah Meth Cops Project were assessed before and after a treatment program involving gradual exercise, comprehensive nutritional support and physical sauna therapy. Evaluations included pre- and post-treatment scores of the Research and Development Corporation (RAND) 36-item Short Form Health Survey (SF-36) in comparison with RAND population norms, pre- and post-treatment symptom score intensities, neurotoxicity scores, Mini-Mental Status Examination, presenting symptom frequencies and a structured evaluation of treatment program safety. RESULTS: Statistically significant health improvements were seen in the SF-36 evaluations, symptom scores and neurotoxicity scores. The detoxification protocol was well tolerated, with a 92.8% completion rate. CONCLUSIONS: This investigation strongly suggests that utilizing sauna and nutritional therapy may alleviate chronic symptoms appearing after chemical exposures associated with methamphetamine related law enforcement activities. This report also has relevance to addressing the apparent ill effects of other complex chemical exposures. In view of the positive clinical outcomes in this group, broader investigation of this sauna based treatment regimen appears warranted. PMID- 22089659 TI - Prevention of rat breast cancer by genistin and selenium. AB - Breast cancer is the second leading cause of cancer death among women and the third most common cancer. In this study, we investigated the chemoprevention efficacy of each of soy genistin, selenium or a combination of them against breast cancer. Seventy-five female rats were divided into five groups : control group (I); 7,12-dimethylbenz(a)anthracene (DMBA) group (II); DMBA treated with genistin group (III); DMBA treated with selenium group (IV); and DMBA treated with genistin combined with selenium group (V). The treatments were daily administered for 3 months. There were a significant decrease in body weight and serum total antioxidant, while a significant elevation in serum total sialic acid, carcinoembryonic antigen, prolactin, estradiol, nitric oxide, and malondialdhyde of DMBA injected rats compared with control group. Administration of genistin and selenium was associated with decreasing levels of tumorigenicity, endocrine derangement, and oxidative stress. Formation of breast carcinoma in DMBA-induced rats and abnormal changes were ameliorated in the rats treated with genistin/selenium or genistin alone. Supplementation of genistin alone or with selenium provided antioxidant defense with high-potential chemopreventive activity against DMBA-induced mammary tumors more than selenium alone. PMID- 22089660 TI - Proposal for the standardisation of multi-centre trials in nuclear medicine imaging: prerequisites for a European 123I-FP-CIT SPECT database. AB - PURPOSE: Multi-centre trials are an important part of proving the efficacy of procedures, drugs and interventions. Imaging components in such trials are becoming increasingly common; however, without sufficient control measures the usefulness of these data can be compromised. This paper describes a framework for performing high-quality multi-centre trials with single photon emission computed tomography (SPECT), using a pan-European initiative to acquire a normal control dopamine transporter brain scan database as an example. METHODS: A framework to produce high-quality and consistent SPECT imaging data was based on three key areas: quality assurance, the imaging protocol and system characterisation. Quality assurance was important to ensure that the quality of the equipment and local techniques was good and consistently high; system characterisation helped understand and where possible match the performance of the systems involved, whereas the imaging protocol was designed to allow a degree of flexibility to best match the characteristics of each imaging device. RESULTS: A total of 24 cameras on 15 sites from 8 different manufacturers were evaluated for inclusion in our multi-centre initiative. All results matched the required level of specification and each had their performance characterised. Differences in performance were found between different system types and cameras of the same type. Imaging protocols for each site were modified to match their individual characteristics to produce comparable high-quality SPECT images. CONCLUSION: A framework has been designed to produce high-quality data for multi-centre SPECT studies. This framework has been successfully applied to a pan-European initiative to acquire a healthy control dopamine transporter image database. PMID- 22089661 TI - Brain hypermetabolism in amyotrophic lateral sclerosis: a FDG PET study in ALS of spinal and bulbar onset. AB - PURPOSE: To identify the neurobiological traits of amyotrophic lateral sclerosis (ALS) and to elucidate functional differences between ALS of spinal and bulbar onset. We hypothesized that glucose metabolism distribution might vary between groups. METHODS: The study groups comprised 32 patients with ALS of either bulbar (n = 13) or spinal (n = 19) onset and 22 subjects as controls. They were investigated by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (FDG PET), comparing the patient groups with each other and with the controls by statistical parametric mapping. RESULTS: Highly significant relative increases in glucose metabolism distribution were found in the group comprising all 32 ALS patients as compared with the controls in the bilateral amygdalae, midbrain, pons and cerebellum. Relative hypermetabolism was also found in patients with spinal onset as compared with the controls in the right midbrain. In patients with bulbar onset compared with the controls and with patients with spinal onset, large relatively hypometabolic areas were found in the bilateral frontal cortex, right insula, anterior cingulate, precuneus and inferior parietal lobe. Patients with spinal onset had significantly higher scores in a neuropsychological test assessing verbal fluency compared with patients with bulbar onset. CONCLUSION: This large FDG PET investigation provided unprecedented evidence of relatively increased metabolism in the amygdalae, midbrain and pons in ALS patients as compared with control subjects, possibly due to local activation of astrocytes and microglia. Highly significant relative decreases in metabolism were found in large frontal and parietal regions in the bulbar onset patients as compared with the spinal onset patients and the controls, suggesting a differential metabolic and neuropsychological state between the two conditions. PMID- 22089662 TI - Standardisation and harmonisation boost the credibility of nuclear medicine procedures. PMID- 22089663 TI - VSL#3 probiotics regulate the intestinal epithelial barrier in vivo and in vitro via the p38 and ERK signaling pathways. AB - Probiotics can play a role in enhancing intestinal barrier function. However, the underlying mechanisms are not fully understood. The aim of this study was to examine the effects of VSL#3 probiotics on colonic epithelium permeability, tight junction protein expression and MAPKs signaling pathways in vivo and in vitro. In vivo, acute colitis was induced by administration of 3.5% dextran sodium sulfate for 7 days. Rats in two groups were treated with either 15 mg VSL#3 or placebo via a gastric tube once daily after induction of colitis. Tight junction protein expression and the MAPKs signaling pathways were studied by immunohistochemistry and immunoblotting. In vitro, HT-29 cells were exposed to TNF-alpha for up to 48 h with or without pre-treatment with a p38 MAPK inhibitor, an ERK inhibitor or a JNK inhibitor. Then tight junction proteins and the phosphorylation of MAPKs were examined in the presence or absence of VSL#3. In vivo, VSL#3 probiotics significantly ameliorated the disease activity index from Day 4 onward. In acute colitis rats, decreased expression of the tight junction proteins were observed, whereas VSL#3 therapy prevented these changes and increased the expression of phosphorylated p38 (P-p38), and of phosphorylated ERK (P-ERK). In vitro, tight junction proteins, P-p38 and P-ERK in the VSL#3 group were significantly higher than in the control and TNF-alpha groups. The p38 MAPK inhibitor and the ERK inhibitor could effectively prevent this effect. VSL#3 probiotics protected the epithelial barrier and increased the tight junction protein expression in vivo and in vitro by activating the p38 and ERK signaling pathways. PMID- 22089664 TI - C-X...pi halogen and C-H...pi hydrogen bonding: interactions of CF3X (X = Cl, Br, I or H) with ethene and propene. AB - Using FTIR and Raman spectroscopy, the formation of halogen bonded complexes of the trifluorohalomethanes CF(3)Cl, CF(3)Br and CF(3)I with ethene and propene dissolved in liquid argon has been investigated. For CF(3)Br and CF(3)I, evidence was found for the formation of C-X...pi halogen bonded 1:1 complexes. At a higher ratio of CF(3)I/propene, weak absorptions due to a 2:1 complex were also observed. Using spectra recorded at different temperatures, the complexation enthalpies for the complexes were determined to be -5.3(2) kJ mol(-1) for CF(3)Br.ethene, -7.5(2) kJ mol(-1) for CF(3)I.ethene, -5.6(1) kJ mol(-1) for CF(3)Br.propene, -8.8(1) kJ mol(-1) for CF(3)I.propene and -16.5(6) kJ mol(-1) for (CF(3)I.)(2)propene. The complexation enthalpies of the hydrogen bonded counterparts, with CF(3)H as the Lewis acid, were determined to be -4.6(4) kJ mol(-1) for CF(3)H.ethene and -5.1(2) kJ mol(-1) for CF(3)H.propene. For both hydrogen bonded complexes, a blue shift, by +4.8 and +4.0 cm(-1), respectively, was observed for the C-H stretching mode. The results from the cryospectroscopic study are compared with ab initio calculations at the MP2/aug-cc-pVDZ(-PP) level. PMID- 22089665 TI - Role of the Fc region in CD70-specific antibody effects on cardiac transplant survival. AB - BACKGROUND: The role of the CD70-specific antibody and the mechanisms by which it extends transplant survival are not known. METHODS: Fully major histocompatibility complex-mismatched heterotopic heart transplantation (BALB/c to C57BL/6) was performed. Treated mice received intraperitoneal injections of wild-type (WT) CD70-specific antibody (FR70) or IgG1 or IgG2a chimeric antibodies on days 0, 2, 4, and 6 posttransplantation. RESULTS: WT FR70 antibody significantly extended heart transplant survival to 19 days compared with untreated mice (median survival time [MST]=10 days). Graft survival using the nondepleting IgG1 antibody was significantly shorter (MST=14 days), whereas the survival using depleting IgG2a antibody (MST=18) was similar to that using WT FR70. The FR70 and IgG2a antibodies demonstrated a greater efficiency of fixing mouse complement over the IgG1 variant in vitro. CD4 and CD8 T-cell graft infiltration was reduced with treatment; however, this was most pronounced with WT FR70 and IgG2a antibody therapy compared with the IgG1 chimeric variant. Circulating donor-specific IgG alloantibodies were initially reduced with WT FR70 treatment (day 8 posttransplantation) but increased at days 15 and 20 posttransplantation to the level detected in untreated controls. CONCLUSION: We conclude that WT (FR70) and the IgG2a depleting variant of CD70-specific antibody reduce graft infiltrating CD4 and CD8 T cells, transiently reduce serum alloantibody levels, and extend graft survival. In contrast, the nondepleting IgG1 variant of this antibody showed lower efficacy. These data suggest that a depleting mechanism of action and not merely costimulation blockade plays a substantial role in the therapeutic effects of CD70-specific antibody. PMID- 22089667 TI - [An unusual outbreak of histoplasmosis in residents of the state of Mexico]. AB - OBJECTIVE: The aim of this study was to establish whether there was a histoplasmosis outbreak among a group of residents of Naucalpan (State of Mexico, a non-endemic area for histoplasmosis) and to ascertain the source through which they were infected. MATERIAL AND METHODS: Anyone associated with the Index Case in the same period with a flu-like infection was considered as a suspected case. Diagnosis was confirmed by clinical examination positive, cultures and positive immunological tests. Date and form of potential exposure were obtained through interviews. Material potentially contaminated with bird or bat droppings was sought and analyzed by PCR. RESULTS: The outbreak was associated with a trip to El Tamarindo (Veracruz, near the Gulf of Mexico). Patients got sick after digging a hole in the floor inside a house where a treasure had been supposedly buried by a death relative. The pathogen was detected in soil samples at 10 cm below the surface. CONCLUSIONS: The study showed that patients contracted histoplasmosis in El Tamarindo, a community where there had been no prior cases of this disease. PMID- 22089668 TI - [Impact of problem-based learning on the cognitive processes of medical students]. AB - The problem based learning (PBL) method was conceived as a teaching strategy to be applied in different areas or disciplines, thus several universities adopted it, among which was the Universidad Nacional Autonoma de Mexico, best known as UNAM. The Faculty of Medicine of UNAM implemented this innovative teaching method of medicine for its learner-centered educational method tendency (patient centered practice). This method develops also several abilities in the students, such as active and significant learning, seeking and data selection and autoanalysis and synthesis, knowledge integration of, mind's logic for the detection and solution of problems, among others. The aim was to evaluate the PBL impact on pedagogical and cognitive processes through the students' critical thinking and the significance of the experience on students and teachers which were working with PBL; in addition, study strategies and self-regulation in students were considered variables for the study. Our findings indicated that PBL was perceived differently among students and teachers, and it influenced in a positive and significant way the students' perception to solve problems and their motivation to achieve a good academic performance (p < 0.005). These results suggest that PBL is a useful strategy in the teaching and learning process and it is clear that the pedagogical process and other variables can potentially influence the results obtained. PMID- 22089666 TI - Insulin degradation by acinar cell proteases creates a dysfunctional environment for human islets before/after transplantation: benefits of alpha-1 antitrypsin treatment. AB - BACKGROUND: Pancreatic acinar cells are commonly cotransplanted along with islets during auto- and allotransplantations. The aims of this study were to identify how acinar cell proteases cause human islet cell loss before and after transplantation of impure islet preparations and to prevent islet loss and improve function with supplementation of alpha-1 antitrypsin (A1AT). METHODS: Acinar cell protease activity, insulin levels, and percent islet loss were measured after culture of pure and impure clinical islet preparations. The effect of proteases on ultrastructure of islets and beta-cell insulin granules were examined by transmission electron microscopy. The number of insulin granules and insulin-labeled immunogold particles were counted. The in vivo effect of proteases on islet function was studied by transplanting acinar cells adjacent to islet grafts in diabetic mice. The effects of A1AT culture supplementation on protease activity, insulin levels, and islet function were assessed in pure and impure islets. RESULTS: Islet loss after culture was significantly higher in impure relative to pure preparations (30% vs. 14%, P<0.04). Lower islet purity was associated with increased protease activity and decreased insulin levels in culture supernatants. Reduced beta-cell insulin granules and insulin degradation by proteases were confirmed by transmission electron microscopy. Transplantations in mice showed delayed islet graft function when acinar cells were transplanted adjacent to the islets under the kidney capsule. Supplementation of A1AT to impure islet cultures maintained islet cell mass, restored insulin levels, and preserved islet functional integrity. CONCLUSION: Culture of impure human islet fractions in the presence of A1AT prevents insulin degradation and improves islet recovery. PMID- 22089669 TI - [Familial homozygous hypercholesterolemia due to the c2271delT mutation in the LDL receptor gene, detected exclusively in Mexicans]. AB - We present the case of an 18-years old women with homozygous familial hypercholesterolemia in which a LDL receptor mutation (c2271delT) was found. This mutation has been informed only in Mexicans. The patient was born in Oaxaca, Mexico. She has atypical location of tendinous and tuberous xanthomata, coronary atherosclerosis and multiple valve involvement. The response to ezetimibe/high dose statin therapy was poor. This case is an example of the occurrence of homozygous forms of familial hypercholesterolemia in genetically isolated populations of Mexico. PMID- 22089670 TI - [Comprehensive model of care for highly specialized hospitals]. AB - In August 2007 the committee was installed to guide and direct medical management to the satisfaction and needs of medical equipment as special ingredient in the pursuit of quality health services that should be granted to the population. PMID- 22089671 TI - [Conceptual role on team work]. AB - The main purpose of this presentation is to provide basic information on the operational and structural design of future health institutions. The analysis should take into account the double purpose of the medical practice: technology and humanism. PMID- 22089672 TI - [Teaching and research in high specialty hospitals]. AB - Education and research are strategic activities leading to development and progress of a hospital, so planning on this matter is fundamental, both in terms of structure and infrastructure. Investment on faculty development and on researchers should be considered beyond the short term. Education should respond to the necessities and research to health priorities through formal agreements with universities and institutes. PMID- 22089673 TI - [Hospital and organizational dynamics of the National Institutes of Health. Relationship with high-specialty hospitals]. AB - In order to primarily encourage medical care, teaching and research activities in high specialty regional hospitals (HSRH), a number of strategies are explored to increase the number of patients cared for, improve the quality and timeliness of care and successfully integrate the function of these hospitals within the care and patient flow model expected by the Federal Government. These strategies include the use of information technology systems as platforms for telemedicine, including tele-imaging, tele-education and telepathology, thus fostering the quality and timeliness of medical care and narrow the relationship between these HSRH with the National Health Institutes. Other strategies such as extra-mural surgery, specific theme workshops, resident rotations, the use of simulators and "Science Weeks" are also explored so as to promote teaching and research. Finally, the reference and counter-reference system and the introduction of pension programs are evaluated as possible strategies supporting resource management. PMID- 22089674 TI - [Monitoring evaluation system for high-specialty hospitals]. AB - Hospital evaluation is a fundamental process to identify medical units' objective compliance, to analyze efficiency of resource use and allocation, institutional values and mission alignment, patient safety and quality standards, contributions to research and medical education, and the degree of coordination among medical units and the health system as a whole. We propose an evaluation system for highly specialized regional hospitals through the monitoring of performance indicators. The following are established as base thematic elements in the construction of indicators: safe facilities and equipment, financial situation, human resources management, policy management, organizational climate, clinical activity, quality and patient safety, continuity of care, patients' and providers' rights and obligations, teaching, research, social responsibility, coordination mechanisms. Monitoring refers to the planned and systematic evaluation of valid and reliable indicators, aimed at identifying problems and opportunity areas. Moreover, evaluation is a powerful tool to strengthen decision making and accountability in medical units. PMID- 22089675 TI - [Performance and remuneration of medical staff]. AB - The creation of highly specialized hospitals projected by the Federal Ministry of Health, under an innovative financing model, offers the ideal place to implement a new project to fulfill medical management needs and characteristics. The goal is to improve the quality of health care through physician satisfaction. The committee's proposals are geared primarily to direct medical management to the satisfaction, desires, and needs of the medical team as an essential ingredient in the pursuit of quality and warmth in health services that should be granted to the population. PMID- 22089676 TI - [First case of HIV-1 subtype C infection in Mexico]. AB - We herein report the first case of HIV-1 subtype C described in Mexico, which was detected in a South African patient who died in Mexico of an AIDS-related non Hodgkin lymphoma. Although HIV-1 subtype B is the predominant virus circulating in Mexico, the case reported highlights the importance of molecular monitoring of the spreading of HIV-1 subtypes. PMID- 22089677 TI - [Intrapancreatic lipoma: a rare mesenquimatous tumor with an uncertain physiopathogenesis]. AB - Intrapancreatic lipoma is a mesenquimal tumor that currently is still considered a strange entity. There are numerous hypotheses about its pathophysiology; however, none has been clarified. Diagnosis is usually incidental, and computed tomography has been performed for other indications, with high sensibility and specificity, making histopathology confirmation unnecessary, hence suggesting image-follow up solely. PMID- 22089678 TI - [A rare case of colorectal micropapillary carcinoma]. AB - Micropapillary carcinoma is regarded as an aggressive variant of adenocarcinoma in any location. It is histologically characterized by papillary cell clusters surrounded by clear spaces. The reported proportion of micropapillary carcinoma component in the entire tumor ranges from 5-80% and no pure cases have been reported. To date, there are approximately 130 cases reported in the colorectum. We recently examined a patient with a pure micropapillary carcinoma showing co expression of CK7, CK20, and absence of CDX2, which had an aggressive tumor with extensive perineural, vascular, and lymphatic invasion as well as extensive nodal metastasis. The presence of a micropapillary carcinoma in the colorectum seemed to be closely related with nodal metastasis, as observed in micropapillary carcinomas from other organs. Thus, if a micropapillary component is identified in a tumor, particularly in a biopsy specimen, extensive surgical resection should be considered due to the high potential for nodal metastasis, even if the preoperative diagnosis is a pedunculated early colorectal cancer. PMID- 22089679 TI - [Agueda of Catania: the patron saint of patients with breast diseases]. AB - For those suffering from breast cancer, Agatha is their patron saint. She was a beautiful Christian maiden, from Catania, Sicily, who dedicated her life to God. As she rejected the love proposals of consul Quintiliano, she suffered cruel tortures. One of the tortures she suffered was to have her breast cut off, with iron shears, a detail that furnished to the Christian medieval iconography, the peculiar characteristic of Agatha. Catania honors Agatha as her patron saint and throughout the region around Mt. Etna. Saint Agatha's feast day is February 5. All of those dedicated to the treatment and prevention of breast cancer are known as "the soldiers of Saint Agatha". PMID- 22089681 TI - Tobacco epidemic in South-East Asia region: challenges and progress in its control. PMID- 22089682 TI - Tobacco use: a major risk factor for non communicable diseases in South-East Asia region. AB - Tobacco use is a serious public health problem in the South East Asia Region where use of both smoking and smokeless form of tobacco is widely prevalent. The region has almost one quarter of the global population and about one quarter of all smokers in the world. Smoking among men is high in the Region and women usually take to chewing tobacco. The prevalence across countries varies significantly with smoking among adult men ranges from 24.3% (India) to 63.1% (Indonesia) and among adult women from 0.4% (Sri Lanka) to 15% (Myanmar and Nepal). The prevalence of smokeless tobacco use among men varies from 1.3% (Thailand) to 31.8% (Myanmar), while for women it is from 4.6% (Nepal) to 27.9% (Bangladesh). About 55% of total deaths are due to Non communicable diseases (NCDs) with 53.4% among females with highest in Maldives (79.4%) and low in Timor Leste (34.4%). Premature mortality due to NCDs in young age is high in the region with 60.7% deaths in Timor Leste and 60.6% deaths in Bangladesh occurring below the age of 70 years. Age standardized death rate per 100,000 populations due to NCDs ranges from 793 (Bhutan) and 612 (Maldives) among males and 654 (Bhutan) and 461 (Sri Lanka) among females respectively. Out of 5.1 millions tobacco attributable deaths in the world, more than 1 million are in South East Asia Region (SEAR) countries. Reducing tobacco use is one of the best buys along with harmful use of alcohol, salt reduction and promotion of physical activity for preventing NCDs. Integrating tobacco control with broader population services in the health system framework is crucial to achieve control of NCDs and sustain development in SEAR countries. PMID- 22089683 TI - Social, economic and legal dimensions of tobacco and its control in South-East Asia region. AB - This paper examines the social, cultural, economic and legal dimensions of tobacco control in the South-East Asia Region in a holistic view through the review of findings from various studies on prevalence, tobacco economics, poverty alleviation, women and tobacco and tobacco control laws and regulations. Methods were Literature review of peer reviewed publications, country reports, WHO publications, and reports of national and international meetings on tobacco and findings from national level surveys and studies. Tobacco use has been a social and cultural part of the people of South-East Asia Region. Survey findings show that 30% to 60% of men and 1.8% to 15.6% of women in the Region use one or the other forms of tobacco products. The complex nature of tobacco use with both smoking and smokeless forms is a major challenge for implementing tobacco control measures. Prevalence of tobacco use is high among the poor and the illiterate. It is higher among males than females but studies show a rising trend among girls and women due to intensive marketing of tobacco products by the tobacco industry. Tobacco users spend a huge percent of their income on tobacco which deprives them and their families of proper nutrition, good education and health care. Some studies of the Region show that cost of treatment of diseases attributable to tobacco use was more than double the revenue that governments received from tobacco taxation. Another challenge the Region faces is the application of uniform tax to all forms of tobacco, which will reduce not only the availability of tobacco products in the market but also control people switching over to cheaper tobacco products. Ten out of eleven countries are Parties to the WHO Framework Convention on Tobacco Control and nine countries have tobacco control legislation. Enforcement of control measures is weak, particularly in areas such as smoke-free environments, advertisement at the point of sale and sale of tobacco to minors. Socio-cultural acceptance of tobacco use is still a major challenge in tobacco control efforts for the governments and stakeholders in the South-East Asia Region. The myth that chewing tobacco is less harmful than smoking tobacco needs to be addressed with public awareness campaigns. Advocacy on the integration of tobacco control with poverty alleviation campaigns and development programs is urgently required. Law enforcement is a critical area to be strengthened and supported by WHO and the civil society organizations working in the area of tobacco control. PMID- 22089684 TI - Tobacco use among youth and adults in member countries of South-East Asia region: review of findings from surveys under the Global Tobacco Surveillance System. AB - BACKGROUND: This paper examines the prevalence of current tobacco use among youth and adults in selected member countries of the South-East Asia Region using the data from school and household-based surveys included in the Global Tobacco Surveillance System. MATERIALS AND METHODS: Global Youth Tobacco Survey (GYTS) data (years 2007-2009) were used to examine current tobacco use prevalence among youth, whereas Global Adult Tobacco Survey (GATS) data (years 2009-2010) were used to examine the prevalence among adults. GYTS is a school-based survey of students aged 13-15, using a two-stage cluster sample design, and GATS is a household survey of adults age 15 and above using a multi-stage stratified cluster design. Both surveys used a standard protocol for the questionnaire, data collection and analysis. RESULTS: Prevalence of current tobacco use among students aged 13-15 varied from 5.9% in Bangladesh to 56.5% in Timor-Leste, and the prevalence among adults aged 15 and above was highest in Bangladesh (43.3%), followed by India (34.6%) and Thailand (27.2%). Reported prevalence was significantly higher among males than females for adults and youth in all countries except Bangladesh, Sri Lanka and Timor-Leste. Current use of tobacco other than manufactured cigarettes was notably higher than current cigarette smoking among youth aged 13-15 years in most countries of the Region, while the same was observed among adults in Bangladesh, India and Thailand, with most women in those countries, and 49% of men in India, using smokeless tobacco. CONCLUSION: Tobacco use among youth and adults in member countries of the region is high and the pattern of tobacco consumption is complex. Tobacco products other than cigarettes are commonly used by youth and adults, as those products are relatively cheaper than cigarettes and affordable for almost all segments of the population. As a result, use of locally produced smoked and smokeless tobacco products is high in the region. Generating reliable data on tobacco use and key tobacco control measures at regular intervals is essential to better understand and respond with effective tobacco control intervention. PMID- 22089685 TI - Evidence building for policy: tobacco surveillance/surveys and research in India. AB - India is at a crucial juncture relating to tobacco control and implementing the recommendations of the WHO FCTC. Tobacco consumption in the country remains alarmingly high in urban as well as rural areas. Smokeless tobacco consumption is very popular among larger masses, including the youth. Cigarette smoking has declined, but bidi use has increased concomitantly. Youth continue to be lured to initiate tobacco consumption through efficient marketing strategies of tobacco companies. The epidemiology of tobacco consumption is markedly varied across the country, with high rates in 15 States. Progress has been made towards tobacco control by the enactment of laws and regulations and the National Tobacco Control Program. Strengthening their implementation and enforcement is the biggest challenge and requires resource inputs. Evidence generation and its translation and utilisation for policy interventions would be useful. PMID- 22089686 TI - WHO framework convention on tobacco control and its implementation in South-East Asia region. AB - The birth of the WHO Framework Convention on Tobacco Control (WHO FCTC) took place in response to the global tobacco epidemic and it became the most important global tobacco control instrument. Duly recognizing tobacco use as an important public health problem and in the wake of rising prevalence of and mortality related to tobacco use, almost all Member States of the South-East Asia Region signed and ratified the WHO FCTC. Following the ratification, Member countries have enacted comprehensive national tobacco control laws and regulations. Most countries have covered some important provisions, such as tax and price measures, smoke-free places, health warnings, a ban on tobacco advertising and promotion, and a ban on tobacco sales to minors. In spite of innumerable constraints and challenges, particularly human, infrastructural and financial resources, Member countries have been doing their best to enforce those legislations and regulations as effectively as possible. In order to educate the general public on the harmful effects of tobacco, mass health campaigns have been organized which are being continued and sustained. However, some of the important areas that need attention in due course of time are tax raises, illicit trade, tobacco industry interference and alternate cropping systems. All Member States in the Region are striving harder to achieving the goals and provisions of the Framework Convention through actively engaging all relevant sectors and addressing the tobacco issue holistically, and thus protecting the present and future generations from the devastating health, social, economic and environmental consequences of tobacco consumption and exposure to tobacco smoke. PMID- 22089687 TI - Second-hand smoke: a neglected public health challenge. AB - Exposure to secondhand smoke (SHS) causes an estimated 5% of the global burden of disease, slightly higher than the burden from direct use of tobacco. This review highlights the urgent need to address this ignored public health issue by presenting the evidence and impact of SHS on those exposed using global studies including those from the South-East Asia Region. The burden of morbidity from SHS exposure is higher in low-income countries in Southeast Asia region compared to the rest of the world. SHS exposure affects those most vulnerable, especially women and children. While several countries in the region have enacted legislation which offer protection to those exposed to SHS, most measures are partial and inadequate. As a result, implementation and compliance at national and sub-national level within the countries of the Southeast Asia region is variable. Governments must ensure that legislation mandates comprehensive smoke free environments in order to provide public health benefit which offers universal protection to everyone and everywhere. Where comprehensive legislation exists, stringent implementation and enforcement, along with awareness building, education and monitoring through regular compliance studies must be done to sustain smokefree status of public places within jurisdictions. PMID- 22089688 TI - Smokeless tobacco: a major public health problem in the SEA region: a review. AB - Smokeless tobacco use is on the upswing in some parts of the world, including parts of SEAR. It is therefore important to monitor this problem and understand the possible consequences on public health. Material for this review was obtained from documents and data of the World Health Organization, co-authors, colleagues, and searches on key words in PubMed and on Google. Smokeless tobacco use in SEAR, as betel quid with tobacco, declined with increased marketing of cigarettes from the early twentieth century. Smokeless tobacco use began to increase in the 1970s in South Asia, with the marketing of new products made from areca nut and tobacco and convenient packaging. As a consequence, oral precancerous conditions and cancer incidence in young adults have increased significantly. Thailand's successful policies in reducing betel quid use through school health education from the 1920s and in preventing imports of smokeless tobacco products from 1992 are worth emulating by many SEAR countries. India, the largest manufacturing country of smokeless tobacco in the Region, is considering ways to regulate its production. Best practices require the simultaneous control of smokeless and smoking forms of tobacco. Governments in SEAR would do well to adopt strong measures now to control this problem. PMID- 22089689 TI - Exposure to tobacco smoke among adults in Bangladesh. AB - OBJECTIVE: To examine exposure to second-hand smoke (SHS) at home, in workplace, and in various public places in Bangladesh. MATERIALS AND METHODS: Data from 2009 Global Adult Tobacco Survey (GATS) conducted in Bangladesh was analyzed. The data consists of 9,629 respondents from a nationally representative multi-stage probability sample of adults aged 15 years and above. Exposure to second-hand smoke was defined as respondents who reported being exposed to tobacco smoke in the following locations: Indoor workplaces, homes, government building or office, health care facilities, public transportation, schools, universities, restaurants, and cafes, coffee shops or tea houses. Exposure to tobacco smoke in these places was examined by gender across various socioeconomic and demographic sub-groups that include age, residence, education and wealth index using SPSS 17.0 for complex samples. RESULTS: The study shows high prevalence of SHS exposure at home and in workplace and in public places. Exposure to SHS among adults was reported high at home (54.9%) (male-58.2% and female-51.7%), in workplace (63%) (male-67.8% and female-30.4%), and in any public place (57.8%) (male-90.4% and female-25.1%) 30 days preceding the survey. Among the public places examined exposure was low in the educational institutions (schools-4.3%) and health care facilities (5.8%); however, exposure was high in public transportation (26.3%), and restaurants (27.6%). SHS exposure levels at home, in workplace and public places were varied widely across various socioeconomic and demographic sub-groups. CONCLUSIONS: Exposure was reported high in settings having partial ban as compared to settings having a complete ban. Following the WHO FCTC and MPOWER measures, strengthening smoke-free legislation may further the efforts in Bangladesh towards creating and enforcing 100% smoke-free areas and educating the public about the dangers of SHS. Combining these efforts can have a complementary effect on protecting the people from hazardous effect of SHS as well as reducing the social acceptance of smoking both at home and in public and workplaces. Ongoing surveillance in Bangladesh is necessary to measure progress towards monitoring SHS exposure. PMID- 22089690 TI - Tobacco control policies in India: implementation and challenges. AB - Tobacco use is a major public health challenge in India with 275 million adults consuming different tobacco products. Government of India has taken various initiatives for tobacco control in the country. Besides enacting comprehensive tobacco control legislation (COTPA, 2003), India was among the first few countries to ratify WHO the Framework Convention on Tobacco Control (WHO FCTC) in 2004. The National Tobacco Control Programme was piloted during the 11 th Five Year Plan which is under implementation in 42 districts of 21 states in the country. The advocacy for tobacco control by the civil society and community led initiatives has acted in synergy with tobacco control policies of the Government. Although different levels of success have been achieved by the states, non prioritization of tobacco control at the sub national level still exists and effective implementation of tobacco control policies remains largely a challenge. PMID- 22089691 TI - Tobacco control: lessons learnt in Thailand. AB - This review of legislation, obstacles faced, and challenges to be met, outlines present tobacco control lessons learnt in Thailand. A review of over twenty years of tobacco control experience in Thailand is provided in seven areas including policy formulation and the role of civil society, as well as in essential WHO Framework Convention on Tobacco Control areas. A descriptive, historical review shows how stakeholders, policies and resources were mobilized in Thailand, and what lessons resource-challenged countries might use from the Thai experience. PMID- 22089692 TI - Local governments and civil society lead breakthrough for tobacco control: lessons from Chandigarh and Chennai. AB - Smoke-free legislation is gaining popularity; however, it must accompany effective implementation to protect people from secondhand smoke (SHS) which causes 600,000 deaths annually. Increasing numbers of smoke-free cities in the world indicate that municipalities have an important role in promoting smoke-free environments. The objectives were to describe the local initiative to promote smoke-free environments and identify the key factors that contributed to the process. Observations were based on a case study on the municipal smoke-free initiatives in Chandigarh and Chennai, India. India adopted the Cigarette and Other Tobacco Products Act in 2003, the first national tobacco control law including smoke-free provisions. In an effort to enforce the Act at the local level, a civil society organization in Chandigarh initiated activities urging the city to support the implementation of the provisions of the Act which led to the initiation of city-wide law enforcement. After the smoke-free declaration of Chandigarh in 2007, Chennai also initiated a smoke-free intervention led by civil society in 2008, following the strategies used in Chandigarh. These experiences resonate with other cases in Asian cities, such as Jakarta, Davao, and Kanagawa as well as cities in other areas of the world including Mexico City, New York City, Mecca and Medina. The cases of Chandigarh and Chennai demonstrate that civil society can make a great contribution to the enforcement of smoke-free laws in cities, and that cities can learn from their peers to protect people from SHS. PMID- 22089694 TI - Two-stage optimization of a supramolecular catalyst for catalytic asymmetric hydroboration. AB - Systematic changes, first to the structure of the catalyst scaffold and then to the ligating groups, are used to fine tune supramolecular catalysts to achieve high regioselectivity (95-98%) and high enantioselectivity (94-97% ee) across a series of meta-substituted styrenes varying in electronic character. PMID- 22089693 TI - In vitro and in vivo hepatoprotective and antioxidant effects of Astragalus polysaccharides against carbon tetrachloride-induced hepatocyte damage in common carp (Cyprinus carpio). AB - The present study is aiming at evaluating the hepatoprotective and antioxidant effects of Astragalus polysaccharide (APS) on the carbon tetrachloride (CCl(4)) induced hepatocyte and liver injury in common carp in vitro and in vivo. In vitro, APS (200, 400 and 800 MUg/ml) was added to the carp primary hepatocytes before (pre-treatment), after (post-treatment) and both before and after (pre- and post-treatment) the incubation of the hepatocytes with CCl(4) at 8 mM in the culture medium. APS at concentrations of 200, 400 and 800 MUg/ml significantly improved cell viability and inhibited the elevation of glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase (GOT), lactate dehydrogenase (LDH) and malondialdehyde (MDA) and significantly increased the reduced level of superoxide dismutase (SOD). In vivo administration of APS at the doses of 1.5 and 3 g/kg in the diet for 60 days prior to CCl(4) intoxication significantly reduced the elevated activities of GPT, GOT and LDH and increased the reduced levels of total protein and albumin in the serum; meanwhile, the reduced levels of SOD, glutathione and total antioxidant capacity (T-AOC) were markedly increased and the MDA formation was significantly inhibited in liver tissue. Overall results proved the hepatoprotective action of APS, which is likely related to its antioxidant activity. The results support the use of APS as a hepatoprotective and antioxidant agent in fish. PMID- 22089695 TI - Osteoplastic bone metastasis in esophageal squamous cell cancer: report of a case. AB - This report presents a case of esophageal squamous cell cancer with osteoplastic bone metastasis. A 58-year-old male patient underwent multimodality treatment for esophageal cancer. Sclerotic changes resembling bone metastasis from prostate cancer were detected in the 4th thoracic and the 5th lumber vertebral body soon after the adjuvant chemoradiotherapy. Systemic examinations revealed no primary cancer as a cause of osteoplastic bone metastasis and no esophageal cancer recurrence. A needle biopsy revealed metastases of esophageal squamous cell cancer with osteoplastic changes. Multiple sclerotic changes were detected in the systemic bones at that time, and new carcinomatous bilateral pleural effusion developed. The drastic systemic progression of the cancer caused the rapid deterioration of the patient's general condition. PMID- 22089696 TI - Parenchyma-preserving hepatic resection for colorectal liver metastases. AB - BACKGROUND: Hepatic resection of colorectal liver metastases is the only curative treatment option. As clinical and experimental data indicate that the extent of liver resection correlates with growth of residual metastases, the present study analyzes the potential benefit of a parenchyma-preserving liver surgery approach. METHODS: Data from a prospectively maintained database of patients undergoing liver resection for colorectal metastases were reviewed. Evaluation of outcome was performed using the Kaplan-Meier method. Correlations were calculated between clinical-pathological variables. RESULTS: One hundred sixty-three patients underwent 198 liver resections for colorectal metastases: 26 major hepatectomies, 65 minor anatomical resections, 78 non-anatomical resections, as well as 29 combinations of minor anatomical and non-anatomical procedures. Overall 1-, 3-, and 5-year survival was 93%, 62%, and 40%, respectively. Patients with repeated liver resections had a 5-year survival of 27%. Interestingly, large dissection areas were associated with a significant reduction of the 5-year survival rate (33%). Five-year survival after major hepatectomy was not significantly reduced. CONCLUSION: For colorectal liver metastases, minor resections offer a prolonged survival compared to major hepatectomies. As patients with stage IV colorectal disease are candidates for repeat resections, preservation of hepatic parenchyma is of increasing importance in the setting of multi-modal and repeated therapy approaches. PMID- 22089697 TI - How neurons make us jump: the neural control of stretch-shortening cycle movements. AB - How can the human central nervous system (CNS) control complex jumping movements task- and context-specifically? This review highlights the complex interaction of multiple hierarchical levels of the CNS, which work together to enable stretch shortening cycle contractions composed of activity resulting from feedforward (preprogrammed) and feedback (reflex) loops. PMID- 22089699 TI - DABCO-catalyzed regioselective cyclization reactions of beta,gamma-unsaturated alpha-ketophosphonates or beta,gamma-unsaturated alpha-ketoesters with allenic esters. AB - Highly efficient DABCO-catalyzed [4 + 2] cycloaddition of beta,gamma-unsaturated alpha-ketophosphonates or beta,gamma-unsaturated alpha-ketoesters with allenic esters gives the corresponding highly functionalized tetrahydropyran and dihydropyran derivatives in good to excellent yields and moderate to good regioselectivities under mild conditions. PMID- 22089698 TI - cMyBP-C as a promiscuous substrate: phosphorylation by non-PKA kinases and its potential significance. AB - It is now generally accepted that phosphorylation of cMyBP-C is critically important in maintaining normal cardiac function. Although much of the work to date on phospho-regulation of cMyBP-C has focused on the role of protein kinase A (PKA, also known as cAMP-dependent protein kinase), recent evidence suggests that a number of non-PKA serine/threonine kinases, such as Ca(2+)/calmodulin-dependent protein kinase II, protein kinase C, protein kinase D and the 90-kDa ribosomal S6 kinase are also capable of targeting this key regulatory sarcomeric protein. This article reviews such evidence and proposes a hypothetical role for some of the pertinent signalling pathways in phospho-regulation of cMyBP-C in the setting of heart failure. PMID- 22089700 TI - Measuring impulsivity in mice: the five-choice serial reaction time task. AB - RATIONALE: Mice are useful tools for dissecting genetic and environmental factors in relation to the study of attention and impulsivity. The five-choice serial reaction time task (5CSRTT) paradigm has been well established in rats, but its transferability to mice is less well documented. OBJECTIVES: This study aims to summarise the main results of the 5CSRTT in mice, with special focus on impulsivity. METHODS: The 5CSRTT can be used to explore aspects of both attentional and inhibitory control mechanisms. RESULTS: Different manipulations of the task parameters can lead to different results; adjusting the protocol as a function of the main variable of interest or the standardisation of the protocol to be applied to a large set of strains will be desirable. CONCLUSIONS: The 5CSRTT has proven to be a useful tool to investigate impulsivity in mice. PMID- 22089701 TI - Utility of screening for chronic granulomatous disease in patients with inflammatory bowel disease. AB - Chronic granulomatous disease (CGD), a genetically heterogeneous primary X-linked or autosomal recessive immunodeficiency, can manifest with gastrointestinal symptoms, including colitis or Crohn's disease. The frequency of CGD carriers among those with chronic colitis/inflammatory bowel disease is unknown. We underwent a pilot study examining the value of prospectively screening patients with chronic colitis/inflammatory bowel disease (IBD) for either CGD or the carrier state of CGD. No carriers of CGD or patients with CGD were detected among 120 patients. Three patients had inconclusive results and the assay was normal on repeat testing. We conclude that routine screening for CGD was not instructive in this cohort of chronic colitis or IBD patients. PMID- 22089702 TI - 'I didn't really like it, but it sounded exciting': admission to hospital for surgery from the perspectives of children. AB - It is a mark of respect for children that their views around their healthcare are listened to and considered. To date, too little attention has been paid to children's views and experiences of admission to hospital for surgery. This paper presents findings from a constructivist grounded theory study of children's experiences of admission to hospital for surgery (from their perspectives). Age appropriate data collection techniques were used and included interviews with children and their drawings and stories. Ten children, aged 6-12 years, who were admitted to hospital for surgery participated in the research. The children were able to clearly articulate aspects of their experience, including their fears and anxieties, the things they enjoyed and the things that assisted them to cope with their experience. The substantive theory developed was 'children's reframing of their sense of selves to incorporate the experiences of hospitalization and surgery'. Children require information and support to alleviate their anxieties around the time of their surgery. With pressures on children's services, increased day surgery rates and shorter admissions, nurses who care for children around this time are challenged to find ways of knowing each child's story and the fears that they have. PMID- 22089703 TI - [The reamer-irrigator-aspirator (RIA) System]. AB - PROBLEM: Autologous bone transplantation is a treatment of choice in patients with large bone defects. However, the iliac crest bone graft harvest is associated with numerous limitations: low volume of graft, long operation times, acute and chronic pain. SOLUTION: The reamer-irrigator-aspirator (RIA) system is used to harvest large volumes of intramedullar bone graft for surgical procedures that require bone graft, including non-unions, delayed union, and bone loss. SURGICAL TECHNIQUE: The RIA device should be assembled prior to the surgical procedure. The greater trochanter is used as entry point. Following the opening of the trochanteric region, a guide wire should be centrally positioned within the bone canal. Frequent fluoroscopic evaluation should be performed to assure the central position of the guide wire. Apply the advance/withdraw/pause/advance technique to maximize irrigation flow through the RIA. The guide wire could be placed in newly desired position within the condyle of the femur if more bone graft is required. While reaming, monitor the reaming head passage on both the anteroposterior and lateral planes to avoid bone perforation or excessive thinning. Remove the intramedullary bone graft from the graft filter. POSTOPERATIVE MANAGEMENT: Cautious ambulation on the 2nd postoperative day. In case of excessive bone thinning of the femur, partial weight bearing for 4-6 weeks is recommended. RESULTS: The RIA system allows large amounts (25-90 cm3) of high quality bone graft to be harvested. This alternative technique is associated with less donor site morbidity and lower rates of minor and major complications when compared with conventional harvest methods (iliac crest). PMID- 22089704 TI - A first-order magnetic phase transition near 15 K with novel magnetic-field induced effects in Er5Si3. AB - We present magnetic characterization of a binary rare-earth intermetallic compound Er(5)Si(3), crystallizing in Mn(5)Si(3)-type hexagonal structure, through magnetization, heat capacity, electrical resistivity and magnetoresistance measurements. Our investigations confirm that the compound exhibits two magnetic transitions with decreasing temperature, the first one at 35 K and the second one at 15 K. The present results reveal that the second magnetic transition is a disorder-broadened first-order transition, as shown by thermal hysteresis in the measured data. Another important finding is that, below 15 K, there is a magnetic-field-induced transition with a hysteretic effect with the electrical resistance getting unusually enhanced at this transition and the magnetoresistance is found to exhibit intriguing magnetic-field dependence, indicating novel magnetic phase coexistence phenomenon. It thus appears that this compound is characterized by interesting magnetic anomalies in the temperature magnetic-field phase diagram. PMID- 22089705 TI - The cover. Coronary artery occlusion. PMID- 22089706 TI - A piece of my mind. Tall buildings. PMID- 22089707 TI - Statin therapy in primary CVD prevention remains a hot-button topic for some. PMID- 22089708 TI - Evidence fails to support ECG screening for those without heart disease symptoms. PMID- 22089709 TI - Environmental pollutants tied to atherosclerosis. PMID- 22089714 TI - Cardiovascular magnetic resonance imaging for diagnosis of stress cardiomyopathy. PMID- 22089715 TI - Underuse of percutaneous coronary intervention. PMID- 22089716 TI - Biologic therapies for chronic plaque psoriasis and cardiovascular events. PMID- 22089717 TI - Cross-level bias and variations in care. PMID- 22089718 TI - Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. AB - CONTEXT: Interest remains high in cholesteryl ester transfer protein (CETP) inhibitors as cardioprotective agents. Few studies have documented the efficacy and safety of CETP inhibitors in combination with commonly used statins. OBJECTIVE: To examine the biochemical effects, safety, and tolerability of evacetrapib, as monotherapy and in combination with statins, in patients with dyslipidemia. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted among 398 patients with elevated low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels from April 2010 to January 2011 at community and academic centers in the United States and Europe. INTERVENTIONS: Following dietary lead-in, patients were randomly assigned to receive placebo (n = 38); evacetrapib monotherapy, 30 mg/d (n = 40), 100 mg/d (n = 39), or 500 mg/d (n = 42); or statin therapy (n = 239) (simvastatin, 40 mg/d; atorvastatin, 20 mg/d; or rosuvastatin, 10 mg/d) with or without evacetrapib, 100 mg/d, for 12 weeks. MAIN OUTCOME MEASURES: The co-primary end points were percentage changes from baseline in HDL-C and LDL-C after 12 weeks of treatment. RESULTS: The mean baseline HDL-C level was 55.1 (SD, 15.3) mg/dL and the mean baseline LDL-C level was 144.3 (SD, 26.6) mg/dL. As monotherapy, evacetrapib produced dose-dependent increases in HDL-C of 30.0 to 66.0 mg/dL (53.6% to 128.8%) compared with a decrease with placebo of -0.7 mg/dL (-3.0%; P < .001 for all compared with placebo) and decreases in LDL-C of -20.5 to -51.4 mg/dL (-13.6% to -35.9%) compared with an increase with placebo of 7.2 mg/dL (3.9%; P < .001 for all compared with placebo). In combination with statin therapy, evacetrapib, 100 mg/d, produced increases in HDL-C of 42.1 to 50.5 mg/dL (78.5% to 88.5%; P < .001 for all compared with statin monotherapy) and decreases in LDL-C of -67.1 to -75.8 mg/dL (-11.2% to -13.9%; P < .001 for all compared with statin monotherapy). Compared with evacetrapib monotherapy, the combination of statins and evacetrapib resulted in greater reductions in LDL-C (P <.001) but no greater increase in HDL-C (P =.39). Although the study was underpowered, no adverse effects were observed. CONCLUSIONS: Compared with placebo or statin monotherapy, evacetrapib as monotherapy or in combination with statins increased HDL-C levels and decreased LDL-C levels. The effects on cardiovascular outcomes require further investigation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01105975. PMID- 22089719 TI - Number of coronary heart disease risk factors and mortality in patients with first myocardial infarction. AB - CONTEXT: Few studies have examined the association between the number of coronary heart disease risk factors and outcomes of acute myocardial infarction in community practice. OBJECTIVE: To determine the association between the number of coronary heart disease risk factors in patients with first myocardial infarction and hospital mortality. DESIGN: Observational study from the National Registry of Myocardial Infarction, 1994-2006. PATIENTS: We examined the presence and absence of 5 major traditional coronary heart disease risk factors (hypertension, smoking, dyslipidemia, diabetes, and family history of coronary heart disease) and hospital mortality among 542,008 patients with first myocardial infarction and without prior cardiovascular disease. MAIN OUTCOME MEASURE: All-cause in hospital mortality. RESULTS: A majority (85.6%) of patients who presented with initial myocardial infarction had at least 1 of the 5 coronary heart disease risk factors, and 14.4% had none of the 5 risk factors. Age varied inversely with the number of coronary heart disease risk factors, from a mean age of 71.5 years with 0 risk factors to 56.7 years with 5 risk factors (P for trend < .001). The total number of in-hospital deaths for all causes was 50,788. Unadjusted in-hospital mortality rates were 14.9%, 10.9%, 7.9%, 5.3%, 4.2%, and 3.6% for patients with 0, 1, 2, 3, 4, and 5 risk factors, respectively. After adjusting for age and other clinical factors, there was an inverse association between the number of coronary heart disease risk factors and hospital mortality adjusted odds ratio (1.54; 95% CI, 1.23-1.94) among individuals with 0 vs 5 risk factors. This association was consistent among several age strata and important patient subgroups. CONCLUSION: Among patients with incident acute myocardial infarction without prior cardiovascular disease, in-hospital mortality was inversely related to the number of coronary heart disease risk factors. PMID- 22089720 TI - Association of coronary CT angiography or stress testing with subsequent utilization and spending among Medicare beneficiaries. AB - CONTEXT: Coronary computed tomography angiography (CCTA) is a new noninvasive diagnostic test for coronary artery disease (CAD), but its association with subsequent clinical management has not been established. OBJECTIVE: To compare utilization and spending associated with functional (stress testing) and anatomical (CCTA) noninvasive cardiac testing in a Medicare population. DESIGN, SETTING, AND PATIENTS: Retrospective, observational cohort study using claims data from a 20% random sample of 2005-2008 Medicare fee-for-service beneficiaries 66 years or older with no claims for CAD in the preceding year, who received nonemergent, noninvasive testing for CAD (n = 282,830). MAIN OUTCOME MEASURES: Cardiac catheterization, coronary revascularization, acute myocardial infarction, all-cause mortality, and total and CAD-related Medicare spending over 180 days of follow-up. RESULTS: Compared with stress myocardial perfusion scintigraphy (MPS), CCTA was associated with an increased likelihood of subsequent cardiac catheterization (22.9% vs 12.1%; adjusted odds ratio [AOR], 2.19 [95% CI, 2.08 to 2.32]; P < .001), percutaneous coronary intervention (7.8% vs 3.4%; AOR, 2.49 [2.28 to 2.72]; P < .001), and coronary artery bypass graft surgery (3.7% vs 1.3%; AOR, 3.00 [2.63 to 3.41]; P < .001). CCTA was also associated with higher total health care spending ($4200 [$3193 to $5267]; P < .001), which was almost entirely attributable to payments for any claims for CAD ($4007 [$3256 to $4835]; P < .001). Compared with MPS, there was lower associated spending with stress echocardiography (-$4981 [-$4991 to -$4969]; P < .001) and exercise electrocardiography (-$7449 [-$7452 to -$7444]; P < .001). At 180 days, CCTA was associated with a similar likelihood of all-cause mortality (1.05% vs 1.28%; AOR, 1.11 [0.88 to 1.38]; P = .32) and a slightly lower likelihood of hospitalization for acute myocardial infarction (0.19% vs 0.43%; AOR, 0.60 [0.37 to 0.98]; P = .04). CONCLUSION: Medicare beneficiaries who underwent CCTA in a nonacute setting were more likely to undergo subsequent invasive cardiac procedures and have higher CAD-related spending than patients who underwent stress testing. PMID- 22089721 TI - Level of systolic blood pressure within the normal range and risk of recurrent stroke. AB - CONTEXT: Recurrent stroke prevention guidelines suggest that larger reductions in systolic blood pressure (SBP) are positively associated with a greater reduction in the risk of recurrent stroke and define an SBP level of less than 120 mm Hg as normal. However, the association of SBP maintained at such levels with risk of vascular events after a recent ischemic stroke is unclear. OBJECTIVE: To assess the association of maintaining low-normal vs high-normal SBP levels with risk of recurrent stroke. DESIGN, SETTING, AND PATIENTS: Post hoc observational analysis of a multicenter trial involving 20,330 patients (age >=50 years) with recent non cardioembolic ischemic stroke; patients were recruited from 695 centers in 35 countries from September 2003 through July 2006 and followed up for 2.5 years (follow-up ended on February 8, 2008). Patients were categorized based on their mean SBP level: very low-normal (<120 mm Hg), low-normal (120-<130 mm Hg), high normal (130-<140 mm Hg), high (140-<150 mm Hg), and very high (>=150 mm Hg). MAIN OUTCOME MEASURES: The primary outcome was first recurrence of stroke of any type and the secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. RESULTS: The recurrent stroke rates were 8.0% (95% CI, 6.8%-9.2%) for the very low-normal SBP level group, 7.2% (95% CI, 6.4%-8.0%) for the low-normal SBP group, 6.8% (95% CI, 6.1%-7.4%) for the high-normal SBP group, 8.7% (95% CI, 7.9%-9.5%) for the high SBP group, and 14.1% (95% CI, 13.0% 15.2%) for the very high SBP group. Compared with patients in the high-normal SBP group, the risk of the primary outcome was higher for patients in the very low normal SBP group (adjusted hazard ratio [AHR], 1.29; 95% CI, 1.07-1.56), in the high SBP group (AHR, 1.23; 95% CI, 1.07-1.41), and in the very high SBP group (AHR, 2.08; 95% CI, 1.83-2.37). Compared with patients in the high-normal SBP group, the risk of secondary outcome was higher for patients in the very low normal SBP group (AHR, 1.31; 95% CI, 1.13-1.52), in the low-normal SBP group (AHR, 1.16; 95% CI, 1.03-1.31), in the high SBP group (AHR, 1.24; 95% CI, 1.11 1.39), and in the very high SBP group (AHR, 1.94; 95% CI, 1.74-2.16). CONCLUSION: Among patients with recent non-cardioembolic ischemic stroke, SBP levels during follow-up in the very low-normal (<120 mm Hg), high (140-<150 mm Hg), or very high (>=150 mm Hg) range were associated with increased risk of recurrent stroke. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00153062. PMID- 22089722 TI - Cardiovascular science in the service of national strength. PMID- 22089723 TI - Prevention of cardiovascular disease and stroke: meeting the challenge. PMID- 22089724 TI - Rational dispersion for the introduction of transcatheter valve therapy. PMID- 22089725 TI - The cardiovascular biomarker conundrum: challenges and solutions. PMID- 22089726 TI - High-density lipoprotein cholesterol as the Holy Grail. PMID- 22089727 TI - Cardiology in 2011--amazing opportunities, huge challenges. PMID- 22089728 TI - JAMA patient page. Heart failure. PMID- 22089729 TI - Factors associated with brachial-ankle pulse wave velocity in the general population. AB - The present study investigated factors that modify or affect arterial stiffness as assessed by brachial-ankle pulse wave velocity (baPWV) in the general population. Subjects had previously participated in a physical checkup program (n=911), and baPWV and urinary albumin and sodium excretion were also measured. Urine albumin was expressed as the ratio of urine albumin to urine creatinine. Individual salt intake was assessed by estimating 24-h urinary salt excretion and expressed as the ratio of estimated salt intake to body weight. The mean blood pressure and baPWV were 127.1+/-15.2/77.0+/-9.5 mm Hg and 15.9+/-3.3 m s(-1), respectively. Univariate analysis demonstrated that baPWV correlated with various factors including age, blood pressure, electrocardiogram voltage (SV(1)+RV(5)), urine albumin and salt intake. Multivariate regression analysis revealed that electrocardiogram voltage (P<0.001), systolic blood pressure (P<0.0001), urine albumin (P<0.001) and salt intake (P<0.001), independently correlated with baPWV after adjustment for other possible factors. Similar results were obtained for participants not taking any medication. These results suggest that the baPWV value is independently associated with individual salt intake and cardiac and renal damage, and could be a useful procedure for identifying individuals with concealed risk of cardiovascular disease. PMID- 22089730 TI - Effects of leaf hair points of a desert moss on water retention and dew formation: implications for desiccation tolerance. AB - Leaf hair points (LHPs) are important morphological structures in many desiccation-tolerant mosses, but study of their functions has been limited. A desert moss, Syntrichia caninervis, was chosen for examination of the ecological effects of LHPs on water retention and dew formation at individual and population (patch) levels. Although LHPs were only 4.77% of shoot weight, they were able to increase absolute water content (AWC) by 24.87%. The AWC of samples with LHPs was always greater than for those without LHPs during dehydration. The accumulative evaporation ratio (AER) showed an opposite trend. AWC, evaporation ratio and AER of shoots with LHPs took 20 min longer to reach a completely dehydrated state than shoots without LHPs. At the population level, dew formation on moss crusts with LHPs was faster than on crusts without LHPs, and the former had higher daily and total dew amounts. LHPs were able to improve dew amounts on crusts by 10.26%. Following three simulated rainfall events (1, 3 and 6 mm), AERs from crusts with LHPs were always lower than from crusts without LHPs. LHPs can therefore significantly delay and reduce evaporation. We confirm that LHPs are important desiccation-tolerant features of S. caninervis at both individual and population levels. LHPs greatly aid moss crusts in adapting to arid conditions. PMID- 22089732 TI - NHS IT is at the mercy of the civil service and "gifted amateurism". PMID- 22089731 TI - Gastroschisis: one year outcomes from national cohort study. AB - OBJECTIVE: To describe one year outcomes for a national cohort of infants with gastroschisis. DESIGN: Population based cohort study of all liveborn infants with gastroschisis born in the United Kingdom and Ireland from October 2006 to March 2008. SETTING: All 28 paediatric surgical centres in the UK and Ireland. PARTICIPANTS: 301 infants (77%) from an original cohort of 393. MAIN OUTCOME MEASURES: Duration of parenteral nutrition and stay in hospital; time to establish full enteral feeding; rates of intestinal failure, liver disease associated with intestinal failure, unplanned reoperation; case fatality. RESULTS: Compared with infants with simple gastroschisis (intact, uncompromised, continuous bowel), those with complex gastroschisis (bowel perforation, necrosis, or atresia) took longer to reach full enteral feeding (median difference 21 days, 95% confidence interval 9 to 39 days); required a longer duration of parenteral nutrition (median difference 25 days, 9 to 46 days) and a longer stay in hospital (median difference 57 days, 29 to 95 days); were more likely to develop intestinal failure (81% (25 infants) v 41% (102); relative risk 1.96, 1.56 to 2.46) and liver disease associated with intestinal failure (23% (7) v 4% (11); 5.13, 2.15 to 12.3); and were more likely to require unplanned reoperation (42% (13) v 10% (24); 4.39, 2.50 to 7.70). Compared with infants managed with primary fascial closure, those managed with preformed silos took longer to reach full enteral feeding (median difference 5 days, 1 to 9) and had an increased risk of intestinal failure (52% (50) v 32% (38); 1.61, 1.17 to 2.24). Event rates for the other outcomes were low, and there were no other significant differences between these management groups. Twelve infants died (4%). CONCLUSIONS: This nationally representative study provides a benchmark against which individual centres can measure outcome and performance. Stratifying neonates with gastroschisis into simple and complex groups reliably predicts outcome at one year. There is sufficient clinical equipoise concerning the initial management strategy to embark on a multicentre randomised controlled trial comparing primary fascial closure with preformed silos in infants suitable at presentation for either treatment to determine the optimal initial management strategy and define algorithms of care. PMID- 22089733 TI - Gastroschisis. PMID- 22089734 TI - Press releases for government obesity campaign are hidden. PMID- 22089735 TI - Try Google Translate to overcome language barriers. PMID- 22089736 TI - Sudden death in epilepsy. PMID- 22089737 TI - Are you serious about climate change, BMJ? PMID- 22089738 TI - Effects of particulate matter from global burning of biomass. PMID- 22089739 TI - Ensuring quality in primary care. PMID- 22089740 TI - Get the interface right and EHRs can be implemented. PMID- 22089741 TI - Circles--a community response for convicted sex offenders. PMID- 22089742 TI - Armchair philosophising skirts what to do with child sex offenders. PMID- 22089743 TI - Environmental impact of journal distribution is complex. PMID- 22089744 TI - System for disclosing hospitality should be transparent. PMID- 22089745 TI - Ways to communicate the threat of climate change to health. PMID- 22089746 TI - Lessons from strategy game modelling climate change. PMID- 22089747 TI - Cognitive gains of later life are important clinically. PMID- 22089748 TI - What on earth we can do to tackle climate change. PMID- 22089749 TI - Poor hospital hygiene is blamed for deaths of three babies in Bremen. PMID- 22089750 TI - A quarter of diabetic patients miss out on annual foot checks, UK survey warns. PMID- 22089751 TI - Health secretary is ordered to disclose government's assessment of risk posed by NHS changes. PMID- 22089752 TI - Occurrence and fate of androgens, estrogens, glucocorticoids and progestagens in two different types of municipal wastewater treatment plants. AB - The occurrence and fate of fourteen androgens, four estrogens, five glucocorticoids and five progestagens were investigated in two different types of wastewater treatment plants (Plant A: activated sludge with chlorination, and Plant B: oxidation ditch with UV) of Guangdong province, China. 14, 14, and 10 of 28 target compounds were detected in the influent, effluent and dewatered sludge samples with the concentrations ranging from below 1.2 +/- 0.0 ng L(-1) (stanozolol) to 1368 +/- 283 ng L(-1) (epi-androsterone), below 1.0 +/- 0.0 ng L( 1) (progesterone) to 23.1 +/- 1.0 ng L(-1) (5alpha-dihydrotestosterone), 1.0 +/- 0.1 ng g(-1) (estrone) to 460 +/- 4.4 ng g(-1) (5alpha-dihydrotestosterone), respectively. The concentrations of total androgens (1554-1778 ng L(-1) in influent, 13.3-47.8 ng L(-1) in effluent, 377-923 ng g(-1) in dewatered sludge) were much higher than those of total estrogens (41.5-60.2 ng L(-1) in influent, 5.6-13.5 ng L(-1) in effluent, 13.9-57.8 ng g(-1) in dewatered sludge), glucocorticoids (171-192 ng L(-1) in influent, 2.2-6.3 ng L(-1) in effluent, N.D. 4.4 ng g(-1) in dewatered sludge), and progestagens (39.6-40.5 ng L(-1) in influent, 6.9-12.1 ng L(-1) in effluent, N.D. in dewatered sludge) in these two WWTPs. According to mass balance analysis, the removal rates of most target steroids in Plant A had exceeded 90%, while those in Plant B for nearly half of detected target steroids were lower than 80%. It is obvious that the treatment capacity of the activated sludge system (Plant A) is superior to the oxidation ditch (Plant B) in the degradation of steroids in sewage treatment systems. Androgens, estrogens and progestagens were mainly removed by sorption and degradation, while the reduction of glucocorticoids was primarily due to degradation. PMID- 22089753 TI - Effect of mannitol on cerebral blood volume in patients with head injury. AB - BACKGROUND: Mannitol has traditionally been the mainstay of medical therapy for intracranial hypertension in patients with head injury. We previously demonstrated that mannitol reduces brain volume in patients with cerebral edema, although whether this occurs because of a reduction in brain water, blood volume, or both remains poorly understood. OBJECTIVE: To test the hypothesis that mannitol acts by lowering blood viscosity leading to reflex vasoconstriction and a fall in cerebral blood volume (CBV). METHODS: We used O positron emission tomography to study 6 patients with traumatic brain injuries requiring treatment for intracranial hypertension. Cerebral blood flow (CBF), CBV, and cerebral metabolic rate for oxygen (CMRO2) were measured before and 1 hour after administration of 1.0 g/kg 20% mannitol. RESULTS: CBV rose from 4.1 +/- 0.4 to 4.2 +/- 0.2 mL/100 g (P = .3), while intracranial pressure fell from 21.5 +/- 4.9 to 13.7 +/- 5.1 mm Hg (P < .003) after mannitol. Blood pressure, PaCO2, oxygen content, CBF, and CMRO2 did not change. CONCLUSION: A single bolus of 1 g/kg of 20% mannitol does not acutely lower CBV. Another mechanism, such as a reduction in brain water, may better explain mannitol's ability to lower intracranial pressure and reduce mass effect. PMID- 22089754 TI - Vein of Galen malformations in neonates: new management paradigms for improving outcomes. AB - BACKGROUND: Untreated patients with symptomatic neonatal presentation of vein of Galen aneurismal malformations (VGAMs) carry almost 100% morbidity and mortality. Medical management and endovascular techniques for neonatal treatment have significantly evolved. OBJECTIVE: To evaluate the clinical and angiographic outcomes of modern management of neonates with refractory heart failure from VGAMs. METHODS: From 2005 to 2010, 16 neonatal patients with VGAM presented to our institution. Medical care from the prenatal to perinatal stages was undertaken according to specified institutional guidelines. Nine patients with refractory heart failure required neonatal endovascular intervention. All patients were treated by transarterial deposition of n-butyl cyanoacrylate into fistula sites. Short- and long-term angiographic studies and clinical outcomes were reviewed. RESULTS: Control of heart failure was achieved in 8 patients. One premature baby died shortly after treatment. Long-term angiographic follow-up shows total or near-total angiographic obliteration in all 8 patients. One patient has a mild hemiparesis from treatment. Another has a mild developmental delay. One patient developed a severe seizure disorder and developmental delay. Overall, 66.7% patients have normal neurological development with near-total or total obliteration of the malformation. CONCLUSION: Treatment of refractory heart failure in neonatal VGAM with modern prenatal, neurointensive, neuroanesthetic, and pediatric neuroendovascular care results in significantly improved outcomes with presumed cure and normal neurological development in most. PMID- 22089755 TI - Low pulsatility index on transcranial Doppler predicts symptomatic large-vessel vasospasm after aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Elevated mean cerebral blood flow velocity (mCBFV) on transcranial Doppler predicts vasospasm of the large intracranial arteries after aneurysmal subarachnoid hemorrhage (aSAH). The pulsatility index (PI) is a measure of distal vascular resistance, which may be low when there is compensatory distal vasodilatation following hypoperfusion caused by large-vessel vasospasm. OBJECTIVE: To study the predictive value of low PI for symptomatic large-vessel vasospasm (SLVVS) after aSAH. METHODS: Medical records of patients admitted with aSAH between January 2007 and April 2009 were reviewed. Transcranial color-coded duplex (TCCD) sonography was performed daily between days 2 and 14. Patients with unexplained acute neurological decline underwent catheter- or computed tomography angiography. The lowest recorded PI and the highest mCBFV on TCCD were correlated to the occurrence of SLVVS, angiographic vasospasm, and delayed cerebral infraction in multivariate analysis by use of logistic regression. Functional outcome was assessed at first follow-up. RESULTS: Eighty-one patients met inclusion criteria. Mean lowest PI was 0.71 + 0.19. Median highest mCBFV was 135 cm/s (interquartile range 99-194 cm/s). SLVVS was seen in 21 of 81 (26%) patients, whereas 27 of 55 (49%) patients with repeat angiography had moderate or severe angiographic vasospasm. Following multivariate analysis, only the lowest PI was an independent predictor of SLVVS (P = .03, odds ratio 0.04, 95% confidence interval 0.001-0.54), whereas only the highest mCBFV was an independent predictor of angiographic vasospasm (P = .02, odds ratio 1.01, 95% confidence interval 1.002-1.02). SLVVS was independently associated with functional outcome at follow-up. CONCLUSION: Low PI on TCCD is an independent predictor of SLVVS after aSAH, whereas mCBFV is a better predictor of angiographic vasospasm. PMID- 22089756 TI - Differential expression of folate receptor alpha in pituitary adenomas and its relationship to tumor behavior. AB - BACKGROUND: Folate receptor alpha (FRalpha) plays a pivotal role in the tumorigenesis of some malignant tumors, but its role and clinical significance in pituitary adenomas remain unclear. OBJECTIVE: To identify a possible biomarker for the diagnosis of nonfunctional pituitary adenomas (NFAs) that could also be used to assess tumor behavior. METHODS: Sporadic pituitary tumor specimens (n = 76) and normal pituitary glands (n = 7) were examined. FRalpha protein and mRNA expression were quantified by immunohistochemistry and quantitative reverse transcriptase polymerase chain reaction, respectively. We verified the differential expression of FRalpha in pituitary adenomas and evaluated the associations of FRalpha expression with Ki-67 labeling index (LI) and clinicopathologic characteristics of NFAs. Statistical significance was determined by using the Student t test or one-way analysis of variance. RESULTS: FRalpha mRNA and protein was uniquely overexpressed in NF (immunohistochemically positive) and NF (immunohistochemically negative) adenomas but not in functional adenomas (adrenocorticotropic hormone, growth hormone, and prolactin) or normal adenohypophysial tissues (P < .001). The expression of FRalpha was positively correlated with tumor invasiveness, size and Ki-67 LI in NFAs. CONCLUSION: FRalpha may play an important role in the development and progression of NFAs. Therefore, FRalpha may be useful as a molecular biomarker for the diagnosis of NFAs and assessment of tumor invasiveness. PMID- 22089757 TI - Identifying the trigeminal nerve branches for transovale radiofrequency thermolesion: "no pain, no stress". AB - BACKGROUND: Radiofrequency thermorhizotomy of the trigeminal nerve is a known treatment of trigeminal neuralgia. Analysis of verbal responses to electric stimulation of the trigeminal rootlets has been the only method available to localize the affected branch, but patient discomfort may lead to unreliable verbal responses, resulting in increased morbidity or even therapeutic failure. Orthodromically elicited evoked potentials of the trigeminal nerve have also been used, but their application is tedious and results may vary. OBJECTIVE: To develop an electrophysiological method for intraoperative localization of the trigeminal nerve branches. METHODS: A series of 55 patients under general anesthesia during radiofrequency thermorhizotomy were studied. The trigeminal nerve root was stimulated through the foramen ovale with the RF electrode. Antidromic responses were recorded from the 3 divisions of the trigeminal nerve in the face. Effectiveness rate, pain relief, recurrence, complications, and patient comfort after the procedure were analyzed. RESULTS: Reproducible and easily obtained antidromic responses were clearly recorded in every subdivision of the trigeminal nerve in all patients. Ninety-four percent of patients experienced immediate pain relief after the procedure. The recurrence rate was 12.72%, and the surgical morbidity was 20%. CONCLUSION: This method proved to be useful to determine the exact localization of individual subdivisions of the trigeminal nerve in anesthetized patients, making this procedure safer and more comfortable for them. PMID- 22089758 TI - Optimal surgical approaches for Rathke cleft cyst with consideration of endocrine function. AB - BACKGROUND: Surgical indications for Rathke cleft cyst are not clear. OBJECTIVE: To evaluate postoperative outcomes in terms of endocrine function. METHODS: The study analyzed a total 73 patients who underwent transsphenoidal surgery. All patients underwent a visual field test, combined pituitary function test, and magnetic resonance imaging before and after surgery. A follow-up combined pituitary function test was performed at 1.5-year intervals. RESULTS: The mean age at the time of surgery was 35 +/- 14 years, and the male/female ratio was 1:1.25 (33/40). The mean follow-up duration after surgery was 59 +/- 39 months. The most common symptoms were headache (84%), visual disturbance (48%), and polyuria (38%). After transsphenoidal surgery, 75% of polyuria and 96% of visual field defects were resolved, and pituitary function improved in 42% of patients. The mean age of patients who exhibited worsened hypopituitarism was significantly higher than that of patients who exhibited unchanged or improved hypopituitarism (44 +/- 15.7 vs 33 +/- 13.5 years; P = .02). Twelve patients (16%) experienced recollection of cyst, but none required reoperation. Five of the recollected cysts presented with characteristics that were different from those of the initial lesions, and 2 recollected cysts underwent spontaneous regression. CONCLUSION: Minimal incision with radical removal of cyst content is reasonable to prevent the development of endocrine disturbances and other complications. Individualized risks and benefits must be assessed before a decision is reached regarding surgery and surgical method. Patients with recurrent Rathke cleft cyst require careful follow-up with special attention rather than a hasty operation. PMID- 22089759 TI - The association of reamed intramedullary nailing and long-term cognitive impairment. AB - OBJECTIVES: To examine the association of reamed intramedullary nailing (IMN) and long-term cognitive impairment in trauma intensive care unit survivors. DESIGN: Prospective observational cohort. SETTING: Academic Level I trauma center. PATIENTS: One hundred seventy-three patients with multiple trauma (Injury Severity Score greater than 15) who presented to a Level I trauma intensive care unit from July 2006 to July 2007 without evidence of intrancranial hemorrhage. INTERVENTION: None. MAIN OUTCOME MEASURE: Twelve-month cognitive impairment defined a priori as two neuropsychological test scores 1.5 standard deviation below the mean or 1 neuropsychologic test score 2 standard deviations below the mean. RESULTS: One hundred eight of 173 patients (62.4%) were evaluated 12 months after injury with a comprehensive battery of neuropsychological tests. There were 18 patients who received a reamed IMN and 14 of 18 (78%) of these patients had cognitive deficit at follow-up. Fracture treatment with a reamed IMN was associated with long-term impairment (27.4% vs 8.2%, P = 0.03). Multivariable logistic regression found that a reamed IMN (odds ratio, 3.2; 95% confidence interval, 0.95-10.9; P = 0.06) was a moderate risk factor for the development of cognitive impairment 12 months after injury after controlling for Injury Severity Score, level of education, intraoperative hypotension, and duration of mechanical ventilation. CONCLUSIONS: Fracture fixation with a reamed IMN is moderately associated with cognitive impairment in this cohort of multiple trauma patients without intrancranial hemorrhage at 1 year postinjury. Orthopaedic trauma research should continue to investigate a potential association of acute fracture management and long-term cognitive outcome. PMID- 22089760 TI - Negative pressure therapy on primarily closed wounds improves wound healing parameters at 3 days in a porcine model. AB - OBJECTIVES: We investigated the role of negative pressure therapy (NPT) in postoperative primary wound treatment and closure. To date, extensive evidence exists demonstrating the benefit of negative pressure dressings in the treatment of open wounds; our experiment tested the hypothesis that negative pressure dressings improve healing of closed (sutured) wounds. METHODS: A porcine model was used to collect data on the characteristics of closed wounds after 3 days of treatment with NPTs as compared with control dressings. RESULTS: In six pigs with a total of 56 wounds, load to failure (N/mm) in controls was 0.348 (standard deviation [SD] 0.109) versus NPT at 0.470 (SD, 0.194) with a P value of 0.001; energy to failure (mJ/mm) in controls was 0.85 (SD, 0.378) versus NPT at 1.128 (SD, 0.638) with a P value of 0.035. Blinded grading of clinical wound appearance and cross-sectional hematoma size were also improved at 72 hours. CONCLUSIONS: NPT dressings applied to surgically closed wounds enhance the healing characteristics of porcine wounds at 3 days. CLINICAL RELEVANCE: We have observed that primarily closed surgical wounds may benefit from treatment with NPT. The benefit of using NPTs may be most pronounced in situations in which wounds are closed under tension, involve considerable soft tissue trauma, or may be at risk of subdermal hematoma formation. PMID- 22089762 TI - Mangosteen leaf extract increases melanogenesis in B16F1 melanoma cells by stimulating tyrosinase activity in vitro and by up-regulating tyrosinase gene expression. AB - Melanin synthesis is stimulated by various effectors, including alpha-melanocyte stimulating hormone (alpha-MSH), cyclic AMP (cAMP)-elevating agents (forskolin, isobutylmethylxantine, glycyrrhizin) and ultraviolet light. Our investigation focused on the identification of the melanogenic efficacy of mangosteen (Garcinia mangostana) leaf extract with regard to its effects on melanogenesis in B16F1 melanoma cells, since it has been known to possess strong anti-oxidant activities. The mangosteen leaf extract was found to stimulate melanin synthesis and tyrosinase activity in a dose-dependent manner without any significant effects on cell proliferation. Cytotoxicity of the extract was measured using a 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the highest concentration of the extract that did not affect cell viability was 32 ug/ml. Formation of melanin from cultured B16F1 melanoma induced by extract treatment was estimated using spectrophotometry. In order to clarify the subsequent mechanism of tyrosinase activation by the extract, the levels of tyrosinase expression in B16F1 melanoma were examined using an intracellular tyrosinase assay and tyrosinase zymography. Up-regulation of intracellular tyrosinase expression seemed to correlate with an increase in microphtalmia associated transcription factor (MITF) protein levels since MITF is the key factor for genes involved in melanogenesis. Both of the results showed that tyrosinase activity was markedly enhanced from extract-treated cells. The overall results suggest that mangosteen leaf extract may be a promising candidate for the treatment of hypopigmentation disorder and useful for self-tanning cosmetic products. PMID- 22089763 TI - Coverage-dependent adsorption geometry of octithiophene on Au(111). AB - The adsorption behavior of alpha-octithiophene (8T) on the Au(111) surface as a function of 8T coverage has been studied with low-temperature scanning tunneling microscopy, high resolution electron energy loss spectroscopy as well as with angle-resolved two-photon photoemission and ultraviolet photoemission spectroscopy. In the sub-monolayer regime 8T adopts a flat-lying adsorption geometry. Upon reaching the monolayer coverage the orientation of 8T molecules changes towards a tilted configuration, with the long molecular axis parallel to the surface plane, facilitating attractive intermolecular pi-pi-interactions. The photoemission intensity from the highest occupied molecular orbitals (HOMO and HOMO - 1) possesses a strong dependence on the adsorption geometry due to the direction of the involved transition dipole moment for the respective photoemission process. The change in molecular orientation as a function of coverage in the first molecular layer mirrors the delicate balance between intermolecular and molecule/substrate interactions. Fine tuning of these interactions opens up the possibility to control the molecular structure and accordingly the desirable functionality. PMID- 22089764 TI - Life experiences of Brazilian men with urinary incontinence and erectile dysfunction following radical prostatectomy. AB - PURPOSE: The objective of this study was to explore the psychosocial meaning and repercussions on lifestyle associated with erectile dysfunction and urinary incontinence (UI) in men following radical prostatectomy. SUBJECTS AND SETTING: Ten men from Southeastern Brazil who underwent radical prostatectomy for prostate cancer were interviewed. All participants underwent treatment at a urology clinic during the period of September 2007 to February 2009. METHODS: A clinical qualitative study was conducted, using semi-structured interviews with open-ended questions. All interviews were recorded and transcribed verbatim. Each man was interviewed once. The average length of the interviews was 37 minutes (range: 16 to 81 minutes). Data from the interviews were subjected to content thematic analysis and development of categories based on psychodynamic references. RESULTS: Three themes were identified: (1) sexuality called into question; (2) a body without governance; and (3) experiencing loss. These men reported difficulties in dealing both with the physical and emotional impotence resulting from the treatment. Urinary incontinence and erectile dysfunction affected their body by accentuating conflicts related to masculinity, triggering subjective feelings of powerlessness, and psychological distress. CONCLUSION: Study respondents assigned multiple psychological meanings to issues related to feelings of powerlessness in general, leading to a narcissistic wound. The men experienced UI as a bodily deficiency, and erectile dysfunction was experienced as a feeling of being devitalized. These results suggest that UI from prostate cancer treatment affects sexuality and self-esteem. PMID- 22089765 TI - Development and validation of an online interactive, multimedia wound care algorithms program. AB - PURPOSE: To provide education based on evidence-based and validated wound care algorithms we designed and implemented an interactive, Web-based learning program for teaching wound care. DESIGN: A mixed methods quantitative pilot study design with qualitative components was used to test and ascertain the ease of use, validity, and reliability of the online program. SUBJECTS AND SETTING: A convenience sample of 56 RN wound experts (formally educated, certified in wound care, or both) participated. METHODS: The interactive, online program consists of a user introduction, interactive assessment of 15 acute and chronic wound photos, user feedback about the percentage correct, partially correct, or incorrect algorithm and dressing choices and a user survey. After giving consent, participants accessed the online program, provided answers to the demographic survey, and completed the assessment module and photographic test, along with a posttest survey. RESULTS: The construct validity of the online interactive program was strong. Eighty-five percent (85%) of algorithm and 87% of dressing choices were fully correct even though some programming design issues were identified. Online study results were consistently better than previously conducted comparable paper-pencil study results. Using a 5-point Likert-type scale, participants rated the program's value and ease of use as 3.88 (valuable to very valuable) and 3.97 (easy to very easy), respectively. Similarly the research process was described qualitatively as "enjoyable" and "exciting." CONCLUSION: This digital program was well received indicating its "perceived benefits" for nonexpert users, which may help reduce barriers to implementing safe, evidence-based care. Ongoing research using larger sample sizes may help refine the program or algorithms while identifying clinician educational needs. Initial design imperfections and programming problems identified also underscored the importance of testing all paper and Web-based programs designed to educate health care professionals or guide patient care. PMID- 22089766 TI - Factors affecting closure of a temporary stoma. AB - PURPOSE: The purpose of the study was to examine time to reversal of a temporary ostomy, reasons for delayed closure, and patient satisfaction with the scheduling of their closure and related hospital care. DESIGN: Cross-sectional, descriptive study. SUBJECTS AND SETTING: The target population comprised patients who underwent creation of a temporary ostomy and reversal surgery within one National Health System Hospital Trust in the United Kingdom. The population served by this Trust are ethnically and socioeconomically diverse, predominantly living in urban areas around Greater London. Sixty-one persons who met inclusion criteria were identified. METHODS: A two-step analytical process was undertaken. First, a literature review examining incidence and causes of delayed stoma closure was undertaken. Second, a postal survey of all patients who had had their stoma closed in 2009 was conducted. Respondents were allowed 2 weeks to complete and return the questionnaire. INSTRUMENT: The survey instrument was developed locally and subjected to content validation using ostomy patients, surgical and nursing colleagues. It consisted of 9 questions querying time from original surgery to closure, reasons for delaying closure surgery beyond 12 weeks, and satisfaction with care. RESULTS: Twenty-seven patients returned their questionnaires, indicating they consented to participate; a response rate of 44%. Half of the respondents (n = 14 [52%]) underwent closure surgery within 6 months of stoma formation; the remaining 48% waited more than 6 months (median: 6.5 months, range: 1.5-26 months). Thirteen patients (48%) reported a delay in receiving their stoma closure; the main reason cited was the need for a course of adjuvant postoperative chemotherapy. Three quarters of respondents (22 [74%]) were satisfied with the overall care they received. CONCLUSION: Findings from this study suggest that stoma closure may be associated with fewest complications if performed before 12 weeks. PMID- 22089768 TI - Technical modifications of ureteroneocystostomy in renal transplantation: an 18 year experience. AB - The treatment of choice for patients with end-stage renal disease is renal transplantation. Urinary tract reconstruction is usually done by anti-reflux ureteroneocystostomy, of which there are several techniques. In this study, a comparison of previous studies related to complications and outcome of various extra-vesical uereteroneocystostomy techniques that were used in our center was made. From the year 1988, when renal transplantation was first performed in our center, we utilized many ureteroneocystostomy techniques including Lich-Grigoir, Barry, Tagochi, and finally Barry-Tagochi. With each conversion, we compared the results of the earlier technique with the new one. In addition, we collected the results of four previous studies conducted by our surgeons and analyzed the complications seen with ureteroneocystostomy. A total of 717 renal transplant recipients were included in our study; 214 of these patients were reimplanted by the Barry-Tagochi technique, 155 cases by the Barry technique, 44 cases by the Tagochi technique, and finally, 304 cases by the Lich-Grigor technique. There was no significant difference in the overall complications, urinary leakage and ureteral stenosis, and obstruction between the four groups. However, complicated hematuria was significantly more frequently seen in the Tagochi group (P = 0.002). Also, the mean time taken for ureteroneocystostomy was longer in the Lich Grigor group (P = 0.001). We found that the Barry-Tagochi technique had an overall incidence of urological complications similar to that of the other extravesical techniques and was less time consuming. PMID- 22089767 TI - Association of Helicobacter pylori IgG antibody with various demographic and biochemical parameters in kidney transplant recipients. AB - Few reports are available regarding the promoting factors that affect Helicobacter pylori (H. pylori) infection in renal transplant (RTx) patients. We report a cross-sectional study that was conducted on a group of stable RTx patients to investigate the relationship of various demographic and biochemical parameters of these patients with serum H. pylori IgG antibody titer as a sign of H. pylori infection. A total of 72 patients who were referred to the clinic for continuing their treatment were enrolled in this study. These patients included 47 males and 25 females. The mean age of the study patients was 44 (+/-12) years. The mean length of time after they received a transplanted kidney was 67.5 (+/ 42) months (median: 62 months). The mean value of serum H. pylori-specific IgG antibody titer among these patients was 3 (+/-4.6) U/mL (median: 1 U/mL), and that of intact parathormone (iPTH) was 18.4 (+/-8.2) pg/mL (median: 16.5 pg/mL). The mean serum magnesium (Mg) was 1.9 (+/-0.20) mg/dL (median: 1.9 mg/dL) and the mean creatinine clearance was 53 (+/-11) mL/min (median: 56 mL/min). In this study population, there was no significant difference in the H. pylori IgG antibody titers, serum iPTH, Mg, calcium, alkaline phosphatase and albumin levels as well as body mass index (BMI) between males and females or diabetics and non diabetics. There was no significant relationship between serum H. pylori IgG antibody titers and the age of the patients, BMI, serum Alb, phosphorus, Ca, serum leptin and serum ALP. Significant negative correlation between serum H. pylori IgG antibody titers and serum Mg (r = -0.30, P = 0.01) and serum iPTH (r = -0.25, P = 0.03) was seen. A significant positive correlation was found between serum H. pylori IgG antibody titer and creatinine clearance (r = 0.26, P = 0.02), and a near-significant positive correlation was found with the duration of RTx (r = 0.20, P = 0.08). Our study shows that the correlation of H. pylori IgG antibody titer with some demographic and biochemical indices in RTx recipients may be different from what has been reported in hemodialysis patients. Larger clinical studies are needed to assess the clinical implications of our findings. PMID- 22089769 TI - Safety and efficacy of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in chronic allograft injury. AB - Angiotensin II plays a crucial role in the development of chronic allograft injury (CAI). Clinical experience with angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blockade (ARBS) in CAI has unfortunately been limited. We carried out a prospective one year single center case controlled study to analyze the effect of ACEI /ARBS on the progression of CAI and in decreasing proteinuria. One hundred patients with CAI were evaluated. Of the 100 patients, 50 were selected to receive ACEI/ ARBS (group 1) and 50 managed without ACEI/ARBS (group 2). Their remaining management was similar in both the groups. Patients with hyperkalemia, history of allergic reactions, ACEI/ARBS intake and pregnancy were excluded. Average time for development of CAI was 19.6 +/- 12.7 months in group 1 vs. 20.8 +/- 12.8 in group 2. In group 1, mean systolic/diastolic BP was 136/82 mmHg at the time of establishment of CAI and 124/76 mmHg at the end of one year, and in group 2, it was 138/86 mmHg vs. 126/80 mmHg, respectively. Mean glomerular filtration rate (GFR) was 48.78 +/- 13.4 in the former vs. 44.23 +/- 8.14 in the latter. ACEI/ARBS administration was associated with stabilization of serum creatinine. GFR was maintained up to one year after CAI. Group 1 had a decrease in proteinuria by 1.41 g/day as compared with group 2 with proteinuria of 0.83 g/day. ACEI/ARBS administration is beneficial in CAI for BP control and significant decrease in proteinuria along with the stabilization of graft function. PMID- 22089770 TI - Association of adequate dialysis parameters with left ventricular hypertrophy in hemodialysis patients. PMID- 22089771 TI - Changes of serum calcium, phosphorus, and parathyroid hormone concentrations and ocular findings among patients undergoing hemodialysis. AB - There are various reports of ocular abnormalities in metabolic disorders. This study was done with the aim to investigate the relationships between the amounts of serum calcium, phosphorus, and parathyroid hormone concentrations and ocular findings in patients undergoing hemodialysis. Fifty eight patients with end stage renal failure undergoing hemodialysis were randomly selected and enrolled in this prospective study. Demographic data, history of diabetes mellitus and hypertension, and duration of hemodialysis were recorded. Serum calcium, phosphorus, alkaline phosphatase (ALP), and parathyroid hormone (PTH) concentrations were measured. Also, blood urea nitrogen (BUN) and weight of the patient was measured just before and three minutes after the hemodialysis. Patients also underwent a complete ocular examination including visual acuity, intraocular pressure (IOP), biomicroscopic examination, and fundoscopy. In univariate analysis, adverse relationships were found between the ocular hypertension and ALP concentration (P = 0.017) and also between the visual acuity and phosphorus concentration (P = 0.033). However, in multivariate regression analysis and with regard to the patients' characteristics and medical history in a multivariate model, no relationships were found between ocular findings and serum calcium, phosphorus, ALP, and PTH concentrations. No relationships were found between the serum concentrations of calcium, phosphorus, ALP, and PTH and ocular findings in patients with end stage renal failure undergoing hemodialysis. PMID- 22089772 TI - The deleterious effect of metabolic acidosis on nutritional status of hemodialysis patients. AB - One of the main causes of protein-energy malnutrition in patients on maintenance hemodialysis (MHD) is metabolic acidosis. The aim of this study was to evaluate the effect of metabolic acidosis on nutritional status in a group of MHD patients with adequately delivered dialysis treatment. Of 165 eligible anuric MHD outpatients with Kt/V >= 1 and no underlying inflammatory diseases, 47 subjects were enrolled. In order to evaluate the effect of different parameters on serum albumin, we measured the pre-dialysis serum albumin, blood pH, serum bicarbonate (HCO 3? ), Kt/V, normalized protein catabolic rate (nPCR) and body mass index (BMI) in these patients. The mean age of the study patients was 55 +/- 13.8 years; there were 22 females and six diabetics. The average Kt/V was 1.22 +/- 0.16, pH was 7.40 +/- 0.15, serum HCO 3? was 23.18 +/- 2.38 mEq/L, serum albumin was 4.03 +/- 0.56 g/dL, nPCR was 1.00 +/- 0.16 g/kg/day, post-dialysis body weight was 58.50 +/- 11.50 kg and BMI was 23.47 +/- 2.70 kg/m 2 . There was a statistically significant direct correlation between serum albumin and BMI (r = 0.415, P = 0.004), and between serum albumin and serum HCO 3 (r = 0.341, P = 0.019). On multiple regression analysis, the predictors of serum albumin were serum HCO3? and BMI (direct effect) and nPCR (inverse effect). In 17 patients on MHD with serum HCO3? <22 mEq/L, there was a significant inverse correlation between HCO 3 and nPCR (r = 0.492, P = 0.045), and these patients had significantly lower serum albumin compared with patients with serum HCO3? >22 mEq/L (P = 0.046). These data demonstrate that patients on MHD with metabolic acidosis had a lower serum albumin concentration despite adequate dialysis treatment. The inverse effect of nPCR on serum albumin concentration in acidotic MHD patients may be due to hypercatabolism in the setting of metabolic acidosis, leading to deleterious effects on the nutritional status of patients on MHD. PMID- 22089773 TI - The effect of L-carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients. AB - Protein energy malnutrition and inflammation are common and usually concurrent in maintenance hemodialysis (MHD) patients. Carnitine, a small molecule involved in fatty acid metabolism, is significantly decreased in long-term HD patients. L Carnitine supplementation may have potential benefits in improving dialysis related disorders. However, there are conflicting reports with regard to the beneficial effects of L-Carnitine supplementation. Hence, the present study was carried out to evaluate the effect of L-Carnitine supplementation on lipid parameters, apoproteins and inflammatory and nutritional markers in HD patients. A total of 35 patients with end-stage renal disease, on MHD for a period of 2 to 5 years were recruited into the study. The study group consisted of 20 patients who received Carnitine supplementation intravenously three times a week after each HD session, at 1 g/dose, while the control group consisted of 15 patients without supplementation with L-Carnitine. Highly sensitive C-reactive protein (hsCRP), total protein, albumin, lipid profile and apoprotein AI and B were determined at baseline and at the end of the study. A significant decrease in the hsCRP levels was observed in the Carnitine-supplemented group (P < 0.05). However, no significant change was observed in the lipid parameters and nutritional markers in the Carnitine-supplemented group. In conclusion, the present study demonstrates the significant benefit of L-Carnitine supplementation on inflammatory status in MHD patients as noted by marked decrease in hsCRP levels in comparison with the control group. PMID- 22089774 TI - Kidney imaging in management of delayed febrile urinary tract infection. AB - We report a cross-sectional study performed to evaluate the imaging findings of 40 children, aged one month to five years (16.65 +/- 14.97 months), who presented with protracted fever of more than 48 hours due to urinary tract infection (UTI). About 85% of the patients had positive Tc99-Dimercaptosuccinic acid (DMSA) scan and 58% had vesicoureteral reflux (VUR). Kidney sonography aided in the diagnosis and treatment in 10% of the patients. Age, sex, presence or laterality of VUR did not contribute to defective DMSA scan (pyelonephritis) (P > 0.05). Delayed diagnosis and treatment of febrile UTI is associated with a high incidence of positive findings of DMSA scan irrespective of age, sex or presence/absence of VUR. In mild VUR, the DMSA scan may be normal while in patients with moderate and severe VUR the DMSA scan is almost always abnormal. Thus, our study shows that a normal DMSA scan can help in ruling out moderate to severe forms of VUR and that cystography remains an excellent and standard tool for the diagnosis of VUR. PMID- 22089775 TI - Renal sonographic parameters in human immunodeficiency virus - infected subjects and relationship to CD4 cell count. AB - Nephropathy in human immunodeficiency virus (HIV)-infected patient is common and constitutes a major cause of endstage kidney disease. CD4 cell count is a useful parameter in the assessment of the degree of immunosuppression among HIV-infected patients. Manifestations of renal disease are thought to be more profound when CD4 cell counts are low. Sonography is a safe and inexpensive method of evaluating renal disease, including renal sizes and degree of echogenicity. Ultrasound examination was carried out prospectively at the University of Benin Teaching Hospital on 120 HIV-infected patients comprising 45 males (37.5%) and 75 females (63.5%). Renal sizes and degree of echogenicity were assessed. Correlation with CD4 + cell counts of the patients was done. Mean CD4 cell count mean was 18.34 +/- 142.18 cells/mm 3 with female patients having a significantly higher cell count compared with males. Seventy-four patients (63.8%) had a cell count of <200 cells/mm 3 . Renal sizes were normal in 85%, small in 7%, and large in 8% of patients. Fifty patients (41.7%) had increased renal echogenicity and 8 (6.7%) had severe increased echo-texture. CD4 cell count did not correlate with renal sizes and echotexture. Results of this study show that large kidneys and marked increase in renal echotexture were not common even in a population of patients where the majority had CD4 cell count < 200 cells/mm 3 . This study shows that increased renal sizes and degree of echogenicity alone are not useful predictors of renal involvement in HIV/AIDS. PMID- 22089776 TI - The safety and efficacy of endoscopic incision of orthotopic ureterocele in adult. AB - Endoscopic incision is a good management option for orthotopic ureterocele. But most of the literature has shown its efficacy only in children. We have done this retrospective study to evaluate the safety and efficacy of endoscopic incision of orthotopic ureterocele in adults. From March 2004 to January 2008, at our center, 26 adults underwent transurethral, transverse incision of an ureterocele. The perioperative data of these patients were retrospectively analyzed. The literature was reviewed to identify all the reported options for management of this relatively rare condition in adults. Unilateral ureterocele was present in 24 patients and two patients had bilateral ureterocele. One patient had associated upper tract stones. Three patients had associated stones in ureterocele. Transurethral, transverse incision of ureterocele was given in all patients. The mean postoperative hospital stay was 50.5 h. Twenty-three patients were available for follow-up at three, six and 12 months. All patients were symptom free. At three months ultrasound and intravenous urography revealed no residual ureterocele but four patients showed residual hydronephrosis, but with a decrease in the grade indicating decompression. Micturating cystourethrography revealed vesico-ureteral reflux (VUR) in two patients and the reflux persisted in one patient even at 6 months. We conclude that in adults, management with endoscopic incision of orthotopic ureterocele is safe and effective. VUR may occur in a few cases. PMID- 22089777 TI - Kidney trauma with underlying renal pathology: is conservative management sufficient? AB - To evaluate the pre-existing renal lesions (PERL) found incidentally during evaluation for blunt renal trauma, determine their importance, and suggest guidelines for effective management, including conservative treatment, we reviewed 180 patients who were hospitalized with blunt renal trauma between 1992 and 2008. Thirty of the 180 (16.6%) patients had PERL, which had been undiagnosed. The mean follow-up was 5 years (range 1-9 years). There were 24 men and 6 women with a mean age of 30 years (range 14-80 years). The most common cause of blunt renal injuries was falls and sports. Renal stones were present in 14 patients, pelvi-ureteric junction obstruction in 12, ectopic kidney in two, and megaureter and renal cyst in one case each. Ureteral stenting was used in four cases, and early nephrectomy was required in the other four. Fourteen patients underwent surgery for the PERL and not trauma, with a pyeloplasty in eight cases, partial nephrectomy in three cases, percutaneous nephrololithotomy in two cases, and ureteroneocystostomy in one case. In our study, the conservative treatment was possible in 73% of cases. We believe the published data support increasing conservative attempts in the hemodynamically stable patient. PMID- 22089778 TI - Simvastatin ameliorates gentamicin-induced renal injury in rats. AB - Gentamicin nephrotoxicity is one of the most common causes of acute renal failure. Simvastatin is one of the antioxidative drugs, which has anti inflammatory and anabolic effects and modulates the immune system. The present study was conducted to assess the effect of simvastatin on ameliorating the gentamicin-induced renal injury in 87 Sprague-Dawley rats, which were allocated randomly to 11 study groups: (A) and (B) groups with only gentamicin in 2 dosages; (C), (D), and (E) gentamicin 50 mg/kg/day and simvastatin with different dosage; (F), (G), and (H) gentamicin 80 mg/kg/day and simvastatin with different dosage; (I) only simvastatin; (J) Injected normal saline; (K) control (no gentamicin and no simvastatin) group. Our study intervention period for injection of drugs was 12 days. Serum creatinine level and clearance were measured in all groups. At the end of the study, the rats were killed and both kidneys were removed and processed for histopathologic examination using the standard methods. The 50 mg/kg/day dose was utilized because it induces a mild form of renal toxicity, whereas the 80 mg/kg/day dose cause a more severe degree of renal injury. Morphologic examination of specimens from all rats was qualitatively assessed with blindness to treatment groups and proximal tubular profiles that were presented in each file were counted. The results demonstrated amelioration of gentamicin-induced renal toxicity in rats by simvastatin due to its antioxidant drug dose-related effect. PMID- 22089779 TI - Acute renal failure: nephrosonographic findings in asphyxiated neonates. AB - To determine the incidence of acute renal failure (ARF) and nephrosonographic findings among asphyxiated neonates, and to correlate this with uric acid levels and the severity of hypoxic encephalopathy, we studied 80 full-term appropriate for-date singleton neonates with perinatal asphyxia, and 30 healthy full-term neonates as controls from March 2006 to February 2007. A detailed history, thorough clinical examination along with investigations, including urine examination, 24-h urine collection, ultrasonography of abdomen and cranium, serum electrolytes, blood urea nitrogen, serum creatinine, and serum uric acid were obtained. ARF developed in 45% (36/80) of the asphyxiated neonates. Forty-eight (60%) neonates showed significant elevation of blood urea and 41 (51.3%) neonates had significant elevation of serum creatinine than the control group (P < 0.001). Sixty-two (77.5%) neonates developed significant elevation of serum uric acid levels, and nephrosonography revealed hyperechogenicity in all of them, while only two among the healthy neonates showed the raised uric acid levels (P < 0.001). Nonoliguric renal failure was seen 28/36 (77.8%) of the neonates with ARF, whereas eight (22.2%) neonates had oliguric renal failure. Eight (27.8%) patients among ARF patients maintained abnormal biochemical parameters after 2 weeks, and of whom four patients died after variable lengths of time with a mortality rate of 11.11%. Kidneys are the most common organs involved in perinatal asphyxia, and uric acid might be a causative factor for failure in addition to hypoxic insult. Routine use of kidney function test, along with abdominal ultrasonography form an important screening tool to detect any additional morbidity in these patients. PMID- 22089780 TI - Obesity and metabolic syndrome in hemodialysis patients: single center experience. AB - Recent evidence highlights the relationship between metabolic syndrome (MS) and increased risk of cardiovascular (CV) diseases. The overall prevalence of the MS is increased in hemodialysis population. To evaluate the prevalence of the MS and obesity in our hemodialysis (HD) patients, we studied 234 HD patients and 34 patients were excluded from the study due to incomplete data at the time of analysis. For the remaining 200 patients, 92% were below the age of 70 years old, 162 (81%) were hypertensive, 90(45%) were diabetic, 54 (27%) had ischemic heart diseases, and 116 (58%) had MS. The incidence of MS in the male and female patients was 50% and 67%, respectively, with a mean abdominal girth more than 94 cm in males and only 14% of the patients revealed abdominal girth measurement below 80 cm in females. We conclude that there is a high prevalence of obesity and MS in our HD patients. Such patients may be at risk of developing morbidities and may benefit from therapy such as lifestyle changes including weight reduction and increased physical activity. PMID- 22089781 TI - Comparison of the number of patients admitted with renal colic during various stages of peri-Ramadan month. AB - Ramadan fasting for Muslims means abstinence from eating, drinking, and smoking from sunrise to sunset. There are concerns whether the occurrence of renal colic increases during the month of Ramadan. In view of the importance of fasting among Muslims, the occurrence of renal colic during Ramadan fasting has been compared during the following periods: two weeks before commencement of Ramadan (stage-1), during the first two weeks (stage-2), the last two weeks (stage-3), and, two weeks after Ramadan (stage-4). This was a prospective observational study, which was carried out in patients with symptoms of renal colic who were referred to the emergency wards in two major hospitals in Iran. During the study period, 610 subjects were admitted with renal colic during the four periods of study; there were 441 males (72.3%) and 169 females (27.7%). The number of patients with renal colic was highest during the first two weeks of Ramadan in comparison with the other periods (stage-1: 157, stage-2: 195, stage-3: 139, stage-4: 119, P < 0.05]. Results from this study show that the number of admissions due to renal colic was high during the first two weeks of Ramadan. However, the number of admissions decreased during the last two weeks of Ramadan and this trend continued after Ramadan. PMID- 22089783 TI - Liposarcoma of spermatic cord. PMID- 22089782 TI - Nocardia infection in a renal transplant recipient. AB - Opportunistic infection occurs in up to 20% renal transplant patients and is associated with a high mortality. We report a 47-year-old diabetic female with 1 year-old deceased donor renal allograft on triple drug immunosuppression. She developed cytomegalovirus retinitis at ten months post-transplant followed by nocardiasis manifested by hemiparesis with comatose state due to lumbar epidural and multiple brain abscesses, in spite of immediately curtailing immunosuppression. She recovered with linezolid and cotrimoxazole and was discharged two weeks later. She is maintaining stable graft function with serum creatinine 1.4 mg/dL on cyclosporin 2.5 mg/kg/day and prednisone10 mg/day with maintenance therapy for nocardiasis. PMID- 22089784 TI - Isolated sarcoid renal granulomatous tubulointerstitial disease. AB - A 37-year-old lady presented with hypercalcemia and acute renal impairment. She had no previous medical problems apart from the use of non steroidal anti inflammatory drugs for nonspecific body pains. Her abdominal ultrasound scan as well as urine studies were nonspecific. Further workup for hypercalcemia (skeletal survey, high resolution computed tomography (CT) of the chest and abdomen, purified protein derivative (PPD) test, serum protein electrophoresis, tumor markers, immunology screening, and Bence Jones proteinuria) was negative. Serum angiotensin converting enzyme was high. Renal biopsy showed extensive lymphocytes and multinucleated giant cells infiltration forming interstitial non necrotizing granulomata. Immune staining as well as staining for acid fast bacilli was negative. The possibility of sarcoid renal granulomata was raised and the patient was started on oral prednisolone with subsequent normalization of renal functions and serum calcium after one month of treatment. PMID- 22089785 TI - Renal cell carcinoma associated with granulomatous reaction. AB - Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by accumulation of epithelioid histiocytes and multinucleate giant cells. The cause of granulomas can be infectious or non infectious. Granulomas have been described within the stroma of malignancies like carcinomas of the breast and colon, seminoma and Hodgkin's lymphoma, where they represent T-cell-mediated reaction of the tumor stroma to antigens expressed by the tumor. Granulomatous reaction in association with renal cell carcinoma (RCC) is uncommon, with only few published reports in the literature. We describe three cases of conventional (clear cell) RCC associated with epithelioid granulomas within the tumor parenchyma. PMID- 22089786 TI - Renal abscess due to Escherichia coli in a child. AB - Among the various intraabdominal abscesses, renal abscess is a rare entity, especially in children and accounts for a number of cases of "missed diagnoses." Drainage of pus and appropriate antibiotic therapy is the gold standard for treatment. Here we report a case of left renal abscess in a 6-year-old female child secondary to renal calculus. The patient presented with abdominal pain and mild fever for three months and the diagnosis was made by X-ray in the kidney, ureter and bladder (KUB) region, intravenous pyelography and ultrasonography of the abdomen. Escherichia coli was isolated from pus obtained by percutaneous drainage under sonographic guidance. The patient responded to intra-venous ceftriaxone, amikacin, and percutaneous drainage. PMID- 22089787 TI - Spontaneous remission of post-transplant recurrent focal and segmental glomerulosclerosis. AB - A 12-year-old girl with a history of steroid and cyclosporine (CsA) resistant nephrotic syndrome owing to focal and segmental glomerulosclerosis (FSGS) has progressed to end-stage renal disease (ESRD) for which she underwent hemodialysis for 18 months before she successfully received a fully matched kidney transplant from her sister at the age of nine years. The post transplantation (Tx) period was marked by an early and massive proteinuria indicating recurrent FSGS for which she received 12 sessions of plasmapheresis (PP); unfortunately, she did not appear to have any response to the PP therapy; thereafter, a conservative management comprising essentially enalapril and losartan has been initiated and was also not successful during the first four months, however, a very gradual response has been noticed to occur after five months of conservative therapy and ultimately, the patient attained complete remission after 21 months of treatment. Amazingly, 15 months after discontinuation of enalapril and losartan, she remained in a complete and sustained remission with a good renal allograft function. To the best of our knowledge, this is the first case ever reported in the literature of a "spontaneous" remission of post transplant recurrent FSGS. PMID- 22089788 TI - Rhabdomyolysis, acute kidney injury and transverse myelitis due to naive heroin exposure. AB - Heroin exposure can cause various complications like seizures, stroke, spongiform encephalopathy, transverse myelopathy, plexopathy, compartment syndrome, rhabdomyolysis and renal failure due to various mechanisms. We report here a young male who smoked heroin for the first time and developed transverse myelitis, rhabdomyolysis and acute kidney injury requiring dialysis. His renal recovery was complete by four weeks, while neurological improvement occurred 8 to 12 weeks later. This case suggests a common pathogenic mechanism of heroin intoxication involving multiple systems of the body. PMID- 22089789 TI - Acute urine retention induced by ceftriaxone. AB - Ceftriaxone is known to cause biliary pseudolithiasis and, rarely, nephrolithiasis. When used in neonates receiving intravenous calcium, fatal lung and kidney calcifications occur. There is no satisfactory explanation for the pseudolithiasis, and the mechanism of stone formation remains unknown. Herein, we report a child with acute urinary retention (AUR) secondary to ceftriaxone therapy. The AUR developed on the second hospital day. The urinary excretion of uric acid was elevated. In retrospect, there was a positive paternal family history of gout and stones. A positive family history of gout or stones is a pointer to the possibility of AUR or urolithiasis in patients on treatment with ceftriaxone. If urinary symptoms develop, it is worth checking for crystalluria. This will avoid many unnecessary investigations and procedures. PMID- 22089790 TI - What makes an effective clinical trainer? AB - This study aims at identifying characteristics and behavioral patterns associated with the ideal tutor in different medical fields. This study is expected to answer two questions, first is effective supervision and how can this be determined? And secondly, what skills and qualities do effective supervisors need? An English limited search was performed in many databases including MEDLINE, BEI, and International ERIC for the last 20 years using many search items to identify characteristics cited in the literature as being important for effective clinical teaching. One hundred thirty two articles identified the review excluded literature relating to research supervision. Findings revealed that some of these investigations relied on the tutor's point of view, others on a resident's or a student's opinion or both. Descriptors for effective clinical teachers were categorized into three main classes: (a) teaching skills (i.e. well prepared, practices evidence-based medicine and believes in its principles and applications, effective, accessible, and provides and accepts both positive and negative feedback), (b) personality (i.e. enthusiastic, respectable, sincere, confident, humanitarian, and compassionate), and (c) attitude (i.e. health advocate, good role-model, encouraging, non-judgmental, aware of learners' growth, well-groomed, and appropriately dressed). Other factors such as the trainer's health (i.e. professional, personal, and spiritual fulfillment) and his/her scholarly activities were also identified. PMID- 22089791 TI - Motor disability in end-stage renal failure: an epidemiological study on Italian dialyzed patients. PMID- 22089792 TI - Presentation of seven members of a family with the Alport's syndrome. PMID- 22089793 TI - Copper sulphate poisoning and exchange transfusion. PMID- 22089794 TI - Arterial embolization for spontaneous rupture of renal cell carcinoma. PMID- 22089795 TI - Uremic bleeding with pericardial and subconjunctival hemorrhage. PMID- 22089796 TI - A five-year etiology and antimicrobial susceptibility patterns of urinary pathogens in children at Princess Rahmah Hospital, Jordan. PMID- 22089797 TI - Hematuria following Karate (Kumite) competitions in females. PMID- 22089798 TI - Urachal mucinous cystadenoma. PMID- 22089799 TI - Groin urinoma: a delayed complication of bladder injury. PMID- 22089800 TI - Antibody-mediated rejection: Importance of lactate dehydrogenase and neutrophilia in early diagnosis. PMID- 22089801 TI - The prevalence of tuberculosis in recipients of renal transplantation. PMID- 22089802 TI - Anti-HCMV IgG positivity rate among renal transplant recipients in Baghdad. AB - In developing countries, the majority of infection by human cytomegalovirus (HCMV) occurs during childhood and continues as a latent infection. By adulthood, almost all the population may show anti-HCMV IgG as positive. This study was undertaken to determine the correlation between the prevalence of HCMV antibodies and HCMV infection during post transplant period among renal transplant patients in Baghdad. 43 renal transplant patients attending three renal transplantation centers, and 40 healthy individuals who served as controls were enrolled in this study. 18 (41.9%) were transplanted recently and they were under post-operative follow-up and 25 (58.1%) were transplanted more than one year ago. Detection of anti-HCMV IgG was carried out using enzyme-linked immunosorbant assay (ELISA). The results revealed that anti-HCMV IgG was significantly higher among renal transplant recipients compared to healthy controls (97.7% vs 85%, P = 0.04). The anti-HCMV IgG positivity rate was not affected by patients' age, sex, and duration after transplantation or immunosuppressive therapy. We conclude that the high anti-HCMV IgG positivity rate among Iraqi renal transplant recipients make them prone to considerable risk of reactivation of HCMV infection. PMID- 22089803 TI - Achievements of kidney disease outcomes quality initiative goals in hemodialysis patients at Jordan University Hospital. AB - This study was conducted to assess the current practice patterns of care for hemodialysis (HD) patients at the Jordan University Hospital Dialysis Center using Dialysis Outcomes Quality Initiative Guidelines as the reference. In a cross-sectional study, we assessed 61 patients on HD. The Kt/V was calculated, and data on serum levels of hemoglobin, iron, ferritin, transferrin saturation, calcium, phosphate, and intact parathormone (PTH) were collected. The values were compared with the dialysis outcomes quality initiative (K/DOQI) recommended target values. Forty-one patients (67.2%) had an arteriovenous fistula as the primary access. The mean hemoglobin level was 10.8 +/- 1.4 g/dL, 9.8% of patients had mean serum ferritin < 100 ng/dL and 14.7% had transferrin saturation < 20%. The mean serum calcium level was 9.1 +/- 0.9 mg/dL and serum calcium level between 8.5 and 10.5 mg/dL was found in 82% of HD patients. The mean serum phosphorus was 3.9 +/- 1.1 mg/dL and 59% of patients had serum phosphorus between 3.5 and 5.5 mg/dL. The mean serum PTH was 364 +/- 315 and 14 patients (23%) had serum PTH between 150 and 300 pg/mL. The achieved standard of HD among our study patients was acceptable and, in many aspects, comparable with the NKF-KDOQI guidelines. However, there is still need to improve the management of anemia and control of hyperparathyroidism. PMID- 22089804 TI - Chronic renal failure in Al-Anbar of Iraq. AB - There is no precise study of the epidemiology and prevalence of chronic renal failure in Al-Anbar, Iraq. Therefore, we studied 230 hemodialysis (HD) patients at the HD unit of Al-Ramadi teaching hospital during the period from April 1, 2008 to April 1, 2009. There were 124 (53%) male patients with a mean age of 48 +/- 18.5 years, and 146 (63%) patients were older than 40 years. The estimated prevalence of chronic renal failure was 141 patients per million population. Diabetes mellitus (33%) and hypertension (22.6%) were the most common causes of chronic renal failure, followed in order by obstructive uropathy in 17.3%, undetermined causes in 14%, pyelonephritis in 4.7%, glomerulonephritis in 4.3%, and polycystic kidney disease in 3.9%. This study suggests that large number of patients with end-stage renal disease (ESRD) have diabetes and hypertension. However, those patients with undetermined cause still form a significant portion of etiology of ESRD, and this reflects late referral combined with diagnostic limitations. PMID- 22089805 TI - Preliminary audit on early identification and management of chronic kidney disease in adults in an acute general medical unit in Sri Lanka. AB - This was the first round of an audit to analyze how closely the National Institute of Clinical Excellence (NICE) guidelines on early identification and management of chronic kidney disease in adults is adhered to by a medical ward in the National Hospital of Sri Lanka. One hundred consecutive patients who were not diagnosed to have chronic kidney disease (CKD) but had risk factors for future development of CKD were selected from the male and female wards of the University Medical Unit, National Hospital, Colombo, Sri Lanka. Data were collected by interviewing patients and from the case notes, and entered on a proforma designed based on the recommendations outlined in the NICE guidelines on the prevention of CKD. Target blood pressure was achieved in 66% (n=66). Urine ward test was performed only in 58% of the patients, and this was positive for protein in 15 patients. Investigations to exclude urinary tract infection were performed in 12%. Measurement of serum creatinine was carried out in 40%, but estimated glomerular filtration rate, albumin:creatinine ratio and protein:creatinine ratio were not carried out in any of the patients. Forty percent of the patients were educated by ward staff regarding CKD, 22% on risk factor modification, 23% regarding renal replacement therapy, 34% regarding dietary modifications and 67% regarding importance of exercise. Twenty-six percent of the patients were not educated on any of the above components. ACEI, ARB and statins were prescribed only in 47%, 9% and 64%, respectively. Although follow-up was indicated in all these patients, it was arranged only in 17%. The concurrence with NICE guidelines on CKD prevention was found to be poor. Strategies for improvement are discussed. PMID- 22089806 TI - Epidemiology of chronic kidney disease in a Sri Lankan population: experience of a tertiary care center. AB - Chronic kidney disease (CKD) is a growing problem in Sri Lanka. Diabetes and hypertension are the main contributors to the disease burden. A new form of CKD of uncertain etiology (CKD-u) is the predominant form of CKD in certain parts of Sri Lanka, threatening to reach epidemic proportions. A cross-sectional descriptive study was carried out over a three-month period at the National Hospital of Sri Lanka to identify the underlying etiologic factors for the disease in a cohort of patients with CKD. A total of 200 patients were studied with a mean age of 50.57 years. Of them, 108 (54%) were in CKD stage V. Majority of the patients were from the western province (137, 68.5%) with only five (2.5%) from provinces with high prevalence of CKD-u. The most common underlying causes of CKD were diabetes (88, 44%) and hypertension (34, 17%). However, in patients younger than 40 years of age the most common cause was glomerulonephritis (20, 42.6%). Diabetes was the most common cause of CKD among patients from the western province (74, 54%). The prevalence of CKD-u was twice as high in patients from areas outside the western province compared with patients from this province (P > 0.05). The low prevalence of CKD-u in the study population could be the result of poor representation of patients from provinces with high prevalence of CKD-u. PMID- 22089807 TI - Self-compatibility of 'Zaoguan' (Pyrus bretschneideri Rehd.) is associated with style-part mutations. AB - The pear cultivar 'Zaoguan' (S(4)S(34)) is the a self-compatible descendant of 'Yali' (S(21)S(34)) * 'Qingyun'(S(4)S(9)). Two self-incompatible cultivars 'Xinya' and 'Yaqing', also S-genotyped as S(4)S(34) for the S-RNase gene, were used as controls. Field pollination data revealed that 'Zaoguan' displayed SC, whereas 'Xinya' and 'Yaqing' showed self-incompatibility (SI) upon self pollination. Reciprocal pollinations between the varieties showed that most of the 'Zaoguan' flowers pollinated with 'Xinya' or 'Yaqing' pollen set fruits but that few of the 'Xinya' or 'Yaqing' flowers set fruit when pollinated with 'Zaoguan' pollen. The pollen performance was monitored with fluorescence microscopy, and we observed that 'Zaoguan' accepted self-pollen as well as 'Xinya' or 'Yaqing' pollen, whereas 'Xinya' or 'Yaqing' rejected self-pollen and 'Zaoguan' pollen. The S(34)-RNase but not the S(4)-RNase could be detected in all selfed progeny of 'Zaoguan'. Comparisons of the 2D-PAGE profiles of the stylar extracts from the three cultivars showed that the S(4)-RNase protein expressed normally, but the S(34)-RNase of 'Zaoguan' was not found. Thus, we concluded that the stylar S(34) products were defective in 'Zaoguan' and that the S (4)-allele functioned normally. The nucleotide sequences of the S(4)- and S(34)-RNase of 'Zaoguan' showed no differences from those of 'Xinya' or 'Yaqing', and they transcribed normally. These results indicate that SC in 'Zaoguan' was due to the loss of the S(34)-RNase caused by unknown post-transcriptional factors. PMID- 22089808 TI - Fe-catalysed oxidative C-H functionalization/C-S bond formation. AB - Iron was used as the catalyst for the direct C-H functionalization/C-S bond formation under mild conditions. Various substrates could afford benzothiazoles in moderate to excellent yields. Preliminary mechanistic studies revealed that pyridine played a crucial role for the high yields and selectivities. PMID- 22089809 TI - Posterior auricular artery-middle cerebral artery bypass for additional surgery of moyamoya disease. PMID- 22089810 TI - Direct arteriovenous fistula at the inferolateral trunk mimicking carotid cavernous fistula without involving the cavernous sinus: a case report. AB - The authors present the case of a 66-year-old female who developed progressive pulsating exophthalmos, a bruit, and conjunctival chemosis 7 months after a head injury. These symptoms, though highly suspicious of carotid cavernous fistula, were caused by an arteriovenous fistula (AVF) between the inferolateral trunk (ILT) and the ophthalmic veins. A direct AVF at the branch of the ILT without involvement of the cavernous sinus is extremely rare, but could occur in the case of acquired AVF since the ILT has some branches around venous structures outside the cavernous sinus. The clinical implications of this case are discussed in terms of the anatomical aspects. PMID- 22089811 TI - Does NAD(P)H oxidase-derived H2O2 participate in hypotonicity-induced insulin release by activating VRAC in beta-cells? AB - NAD(P)H oxidase (NOX)-derived H(2)O(2) was recently proposed to act, in several cells, as the signal mediating the activation of volume-regulated anion channels (VRAC) under a variety of physiological conditions. The present study aims at investigating whether a similar situation prevails in insulin-secreting BRIN-BD11 and rat beta-cells. Exogenous H(2)O(2) (100 to 200 MUM) at basal glucose concentration (1.1 to 2.8 mM) stimulated insulin secretion. The inhibitor of VRAC, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) inhibited the secretory response to exogenous H(2)O(2). In patch clamp experiments, exogenous H(2)O(2) was observed to stimulate NPPB-sensitive anion channel activity, which induced cell membrane depolarization. Exposure of the BRIN-BD11 cells to a hypotonic medium caused a detectable increase in intracellular level of reactive oxygen species (ROS) that was abolished by diphenyleneiodonium chloride (DPI), a universal NOX inhibitor. NOX inhibitors such as DPI and plumbagin nearly totally inhibited insulin release provoked by exposure of the BRIN-BD11 cells to a hypotonic medium. Preincubation with two other drugs also abolished hypotonicity induced insulin release and reduced basal insulin output: 1) N-acetyl-L-cysteine (NAC), a glutathione precursor that serves as general antioxidant and 2) betulinic acid a compound that almost totally abolished NOX4 expression. As NPPB, each of these inhibitors (DPI, plumbagin, preincubation with NAC or betulinic acid) strongly reduced the volume regulatory decrease observed following a hypotonic shock, providing an independent proof that VRAC activation is mediated by H(2)O(2). Taken together, these data suggest that NOX-derived H(2)O(2) plays a key role in the insulin secretory response of BRIN-BD11 and native beta-cells to extracellular hypotonicity. PMID- 22089813 TI - Early migration of an Amplatzer muscular ventricular septal defect occluder device causing severe tricuspid valve obstruction. AB - Percutaneous closure of perimembranous and muscular ventricular septal defects is becoming well established worldwide. We present the case of a 15-year-old girl with postoperative tetrology of Fallot and a residual ventricular septal defect that was closed with Amplatzer device complicated by early device migration and severe tricuspid valve obstruction. PMID- 22089814 TI - Blood cyst of the mitral valve. AB - Blood cysts of the mitral valve are mostly benign diverticuli lined by endothelium and filled with blood and can be safely monitored with echocardiographic follow-up. We report a case of asymptomatic blood cyst of the mitral valve in a 63-year-old woman referred for a systolic murmur. At 3-year echo follow-up, the patient is free from notable clinical events. PMID- 22089815 TI - The Stent for Life project in Italy. AB - In Italy, as in other European countries, public service healthcare presents some disparities that are related to geographical, economic, organizational and structural issues. Although some Italian regions have excellent networks for the treatment of ST-elevation myocardial infarction (STEMI), others still have to develop a model that allows each STEMI patient to receive the best reperfusion treatment. A recent nationwide registry from the Italian Society of Interventional Cardiology (SICI-GISE) showed that efficient STEMI networks cover approximately 50% of the Italian territory. For these reasons, Italy joined the Stent for Life initiative in August 2010 with the primary goal of implementing and defining tailored action programs in order to ensure that the majority of the Italian STEMI population have access to life-saving primary percutaneous coronary intervention. PMID- 22089812 TI - Physiology of potassium channels in the inner membrane of mitochondria. AB - The inner membrane of the ATP-producing organelles of endosymbiotic origin, mitochondria, has long been considered to be poorly permeable to cations and anions, since the strict control of inner mitochondrial membrane permeability is crucial for efficient ATP synthesis. Over the past 30 years, however, it has become clear that various ion channels--along with antiporters and uniporters- are present in the mitochondrial inner membrane, although at rather low abundance. These channels are important for energy supply, and some are a decisive factor in determining whether a cell lives or dies. Their electrophysiological and pharmacological characterisations have contributed importantly to the ongoing elucidation of their pathophysiological roles. This review gives an overview of recent advances in our understanding of the functions of the mitochondrial potassium channels identified so far. Open issues concerning the possible molecular entities giving rise to the observed activities and channel protein targeting to mitochondria are also discussed. PMID- 22089816 TI - Bronchogenic cyst of interatrial septum. AB - Bronchogenic cyst, also known as inclusion cyst, is a type of congenital endodermal heterotropia derived from an abnormal development of the ventral diverticulum of the foregut or the tracheobronchial tree during embryogenesis. Its interatrial localization is extremely rare and making a final diagnosis without surgery challenges the clinician. Herein, we report a 58-year-old male patient who had an interatrial bronchogenic cyst related to transient ischemic attack. PMID- 22089817 TI - An unusual mediastinal outline. AB - Thymoma is the most common primary neoplasm of the anterior mediastinum. We describe the case of a 40-year-old man with asymptomatic thymoma involving the right atrium, and the diagnostic pathway. PMID- 22089818 TI - Gold nanoparticle-based fluorescence immunoassay for malaria antigen detection. AB - The development of rapid detection assays for malaria diagnostics is an area of intensive research, as the traditional microscopic analysis of blood smears is cumbersome and requires skilled personnel. Here, we describe a simple and sensitive immunoassay that successfully detects malaria antigens in infected blood cultures. This homogeneous assay is based on the fluorescence quenching of cyanine 3B (Cy3B)-labeled recombinant Plasmodium falciparum heat shock protein 70 (PfHsp70) upon binding to gold nanoparticles (AuNPs) functionalized with an anti Hsp70 monoclonal antibody. Upon competition with the free antigen, the Cy3B labeled recombinant PfHsp70 is released to solution resulting in an increase of fluorescence intensity. Two types of AuNP-antibody conjugates were used as probes, one obtained by electrostatic adsorption of the antibody on AuNPs surface and the other by covalent bonding using protein cross-linking agents. In comparison with cross-linked antibodies, electrostatic adsorption of the antibodies to the AuNPs surfaces generated conjugates with increased activity and linearity of response, within a range of antigen concentration from 8.2 to 23.8 MUg.mL(-1). The estimated LOD for the assay is 2.4 MUg.mL(-1) and the LOQ is 7.3 MUg.mL(-1). The fluorescence immunoassay was successfully applied to the detection of antigen in malaria-infected human blood cultures at a 3% parasitemia level, and is assumed to detect parasite densities as low as 1,000 parasites.MUL( 1). PMID- 22089819 TI - The herbalome--an attempt to globalize Chinese herbal medicine. AB - The herbalome is a project with the objective of globalizing Chinese herbal medicine (CHM) by clarification of its composition, structure, and function; by establishing a standard resource library; and by interpreting the synergistic and complementary mechanisms of multi-components on multi-targets. In phase I, it focuses on the development of systematic separation methodology for resolving and analyzing the complex components in CHM and establishment of a comprehensive resource library. This review summarizes recent advances in the herbalome project with regard to innovative separation techniques and demonstration of a resource library. PMID- 22089820 TI - EUROanalysis 16--hot Belgrade, summer in the city. PMID- 22089821 TI - Asymmetric Michael addition reactions of 3-substituted benzofuran-2(3H)-ones to nitroolefins catalyzed by a bifunctional tertiary-amine thiourea. AB - The current work reports an organocatalytic strategy for the asymmetric catalysis of chiral benzofuran-2(3H)-ones bearing 3-position all-carbon quaternary stereocenters. Accordingly, highly enantioselective Michael addition reactions of 3-substituted benzofuran-2(3H)-ones to nitroolefins have been developed by utilizing a bifunctional tertiary-amine thiourea catalyst. The reactions accommodate a number of nitroolefins and 3-substituted benzofuran-2(3H)-ones to give the desired chiral benzofuran-2(3H)-one products with moderate to excellent yields (up to 98%) and moderate to very good selectivities (up to 19 : 1 dr and up to 91% ee). Theoretical calculations using the DFT method on the origin of the stereoselectivity were conducted. The effect of the nitroolefin substituent position on the stereoselectivity of the Michael addition reaction was also theoretically rationalized. PMID- 22089822 TI - Olfactory experience modifies semiochemical responses in a bark beetle predator. AB - A typical feature of forest insect pests is their tendency to undergo large fluctuations in abundance, which can jeopardize the persistence of their predaceous natural enemies. One strategy that these predators may adopt to cope with these fluctuations would be to respond to sensory cues for multiple prey species. Another possible adaptation to temporal variation in the prey community could involve the learning of prey cues and switching behavior. We conducted three experiments to investigate the ability of the generalist bark beetle predator Thanasimus dubius (F.) (Coleoptera: Cleridae) to respond to different prey signals and to investigate the effect of olfactory experience. We first conducted a field choice test and a wind tunnel experiment to examine the kairomonal response of individual predators toward prey pheromone components (frontalin, ipsenol, ipsdienol, sulcatol) along with the pine monoterpene alpha pinene, which is a volatile compound from the host of the prey. We also presented semiochemically naive predators with two prey pheromone components, frontalin and ipsenol, alone or associated with a reward. Our results showed that T. dubius populations are composed of generalists that can respond to a broad range of kairomonal signals. Naive T. dubius also were more attracted to ipsenol following its association with a reward. This work constitutes the first evidence that the behavior of a predatory insect involved in bark beetle population dynamics is influenced by previous olfactory experience, and provides a potential explanation for the pattern of prey switching observed in field studies. PMID- 22089823 TI - Species-specific chemical signatures in scale insect honeydew. AB - The quantity and chemical composition of honeydew produced by scale insects may influence wider community structure, but little is known about the detailed chemical composition of the honeydew found in forest ecosystems. We used gas chromatography-mass spectrometry to examine the amino acid and carbohydrate composition of honeydew from three New Zealand communities. Low molecular weight carbohydrates (mono-, di-, and tri-saccharides) were derivatized using a modified trimethylsilyl (TMS) method, and amino and non-amino organic acids were derivatized using methylchloroformate (MCF). These recently developed derivatization methods allowed us to detect atypical compounds such as sugar alcohols, fatty acids, and non-amino organic acids, in addition to the more routinely studied compounds such as sugars and amino acids. Some compounds could not be identified and may be novel. Multivariate analysis showed that honeydew from each scale insect species had a distinctive amino acid and carbohydrate signature. We suggest these chemical signatures may influence the types of consumers that are attracted to different honeydews and may explain the characteristic communities associated with these honeydews. PMID- 22089824 TI - Heart rate variability in complex regional pain syndrome during rest and mental and orthostatic stress. AB - BACKGROUND: Complex regional pain syndrome (CRPS) is a pain condition with regional sensory and autonomic abnormalities in the affected limb. The authors studied systemic autonomic and hemodynamic function in CRPS patients during rest, and during orthostatic and mental arithmetic stress. METHODS: Twenty patients with CRPS and 20 age-, sex-, and body mass index-matched control subjects participated. Mean values of heart rate variability, baroreceptor sensitivity, blood pressure, stroke volume, cardiac output, and total peripheral resistance were estimated during supine rest and 60 degrees tilt-table testing. On a separate day, heart rate variability was also measured during mental arithmetic stress testing induced by a paced auditory serial addition task. RESULTS: Heart rate was increased and heart rate variability reduced in patients with CRPS patients compared with control subjects during rest and mental and orthostatic stress, whereas baroreceptor sensitivity was unaffected. When tilted from supine to upright position, patients with CRPS were not able to preserve cardiac output in comparison with control subjects, and they exhibited an exaggerated increase in the total peripheral resistance. The hemodynamic changes correlated to pain duration but not to pain intensity. CONCLUSION: The increased heart rate and decreased heart rate variability in CRPS suggest a general autonomic imbalance, which is an independent predictor for increased mortality and sudden death. The inability of the patients to protect their cardiac output during orthostatic stress was aggravated with the chronicity of the disease. PMID- 22089825 TI - Establishing oleaginous microalgae research models for consolidated bioprocessing of solar energy. AB - Algal feedstock is the foundation of the emerging algal biofuel industry. However, few algae found in nature have demonstrated the combination of high biomass accumulation rate, robust oil yield and tolerance to environmental stresses, all complex traits that a large-scale, economically competitive production scheme demands. Therefore, untangling the intricate sub-cellular networks underlying these complex traits, in one or a series of carefully selected algal research models, has become an urgent research mission, which can take advantage of the emerging model oleaginous microalgae that have already demonstrated small, simple and tackleable genomes and the potential for large scale open-pond cultivation. The revolutions in whole-genome-based technologies, coupled with systems biology, metabolic engineering and synthetic biology approaches, would enable the rational design and engineering of algal feedstock and help to fill the gaps between the technical and economical reality and the enormous potential of algal biofuels. PMID- 22089826 TI - Biohydrogen production from anaerobic fermentation. AB - Significant progress has been achieved in China for biohydrogen production from organic wastes, particularly wastewater and agricultural residues, which are abundantly available in China. This progress is reviewed with a focus on hydrogen producing bacteria, fermentation processes, and bioreactor configurations. Although dark fermentation is more efficient for hydrogen production, by-products generated during the fermentation not only compromise hydrogen production yield but also inhibit the bacteria. Two strategies, combination of dark fermentation and photofermentation and coupling of dark fermentation with a microbial electrolysis cell, are expected to address this issue and improve hydrogen production as well as substrate utilization, which are also discussed. Finally, challenges and perspectives for biohydrogen production are highlighted. PMID- 22089827 TI - Facilitators and barriers to implementation of an evidence-based parenting intervention to prevent child maltreatment: the Triple P-Positive Parenting Program. AB - The prevention of child maltreatment via parenting interventions requires implementation on a broad scale, which is facilitated by drawing on a multidisciplinary array of service workers located in multiple settings. This underscores the importance of understanding factors that impact worker implementation of evidenced-based parenting and family support interventions. This study involved structured interviews with 174 service providers from several disciplines who had been trained previously in the delivery of the Triple P Positive Parenting Program. These follow-up interviews, conducted an average of about 2 years after professional in-service training, provided the basis for examining predictors of sustained program use. Predictors examined included facilitators and barriers to program use, as well as organizational and provider level characteristics such as attitudes toward evidence-based interventions. Highlighting the importance of a systems-contextual perspective on implementation, several provider and organization-level characteristics significantly predicted program use including provider self-confidence after training, fit of program with ongoing duties, availability of posttraining support, and perceived benefit of intervention for children and families. Implications for prevention and implementation science are discussed in view of the challenges inherent in the field of child maltreatment. PMID- 22089828 TI - Mixed Ising ferrimagnets with next-nearest-neighbour couplings on square lattices. AB - We study Ising ferrimagnets on square lattices with antiferromagnetic exchange couplings between spins of values S = 1/2 and 1 on neighbouring sites, couplings between S = 1 spins at next-nearest-neighbour sites of the lattice and a single site anisotropy term for the S = 1 spins. Using mainly ground state considerations and extensive Monte Carlo simulations, we investigate various aspects of the phase diagram, including compensation points, critical properties and temperature-dependent anomalies. In contrast to previous belief, the next nearest-neighbour couplings, when being of antiferromagnetic type, may lead to compensation points. PMID- 22089829 TI - Revertant mosaicism in Kindler syndrome. PMID- 22089830 TI - Soluble peptide treatment reverses CD8 T-cell-induced disease in a mouse model of spontaneous tissue-selective autoimmunity. AB - Transgenic (Tg) mouse models of autoimmunity have been used to express model antigens that can be recognized by T cells or by autoantibodies. To identify mechanisms of CD8-mediated tissue-specific autoimmune reactions and to identify potential treatments, we generated a double-transgenic (DTg) murine model of autoimmunity by crossing keratin-14 (K14)-soluble chicken ovalbumin (sOVA) mice, which express sOVA predominantly in external ear skin, with OT-I mice whose CD8 T cells express Valpha2/Vbeta5 regions of the TCR and are specific for SIINFEKL peptide (chicken ovalbumin (OVA) peptide 257-264) in association with class I major histocompatibility complex. The K14-sOVA/OT-I DTg mice develop a destructive process selectively targeting the external ear pinnae in the first 6 days of life. The ear bud area develops an intense inflammatory infiltrate of OT I cells. Administration of the SIINFEKL peptide intravenously to pregnant F1 (filial 1, first filial generation of animal offspring from cross-mating two parental types) mice and subsequently intraperitoneally to newborn pups resulted in normal external ear development. Treatment with this self-peptide markedly reduced OT-I cell numbers, as well as downregulated the CD8 co-receptor. This model can be useful in studying localized, tissue-specific, immune-mediated skin disease, and provide information about potential therapies for autoimmune diseases in which specific molecular targets are known. PMID- 22089831 TI - Substance P (SP) induces expression of functional corticotropin-releasing hormone receptor-1 (CRHR-1) in human mast cells. AB - Corticotropin-releasing hormone (CRH) is secreted under stress and regulates the hypothalamic-pituitary-adrenal axis. However, CRH is also secreted outside the brain where it exerts proinflammatory effects through activation of mast cells, which are increasingly implicated in immunity and inflammation. Substance P (SP) is also involved in inflammatory diseases. Human LAD2 leukemic mast cells express only CRHR-1 mRNA weakly. Treatment of LAD2 cells with SP (0.5-2 MUM) for 6 hours significantly increases corticotropin-releasing hormone receptor-1 (CRHR-1) mRNA and protein expression. Addition of CRH (1 MUM) to LAD2 cells, which are "primed" with SP for 48 hours and then washed, induces synthesis and release of IL-8, tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) 24 hours later. These effects are blocked by pretreatment with an NK-1 receptor antagonist. Treatment of LAD2 cells with CRH (1 MUM) for 6 hours induces gene expression of NK-1 as compared with controls. However, repeated stimulation of mast cells with CRH (1 MUM) leads to downregulation of CRHR-1 and upregulation in NK-1 gene expression. These results indicate that SP can stimulate mast cells and also increase expression of functional CRHR-1, whereas CRH induces NK-1 gene expression. These results may explain CRHR-1 and NK-1 expression in lesional skin of psoriatic patients. PMID- 22089832 TI - Identification of telogen markers underscores that telogen is far from a quiescent hair cycle phase. PMID- 22089833 TI - Clinical expression and new SPINK5 splicing defects in Netherton syndrome: unmasking a frequent founder synonymous mutation and unconventional intronic mutations. AB - Netherton syndrome (NS) is a severe skin disease caused by loss-of-function mutations in SPINK5 (serine protease inhibitor Kazal-type 5) encoding the serine protease inhibitor LEKTI (lympho-epithelial Kazal type-related inhibitor). Here, we disclose new SPINK5 defects in 12 patients, who presented a clinical triad suggestive of NS with variations in inter- and intra-familial disease expression. We identified a new and frequent synonymous mutation c.891C>T (p.Cys297Cys) in exon 11 of the 12 NS patients. This mutation disrupts an exonic splicing enhancer sequence and causes out-of-frame skipping of exon 11. Haplotype analysis indicates that this mutation is a founder mutation in Greece. Two other new deep intronic mutations, c.283-12T>A in intron 4 and c.1820+53G>A in intron 19, induced partial intronic sequence retention. A new nonsense c.2557C>T (p.Arg853X) mutation was also identified. All mutations led to a premature termination codon resulting in no detectable LEKTI on skin sections. Two patients with deep intronic mutations showed residual LEKTI fragments in cultured keratinocytes. These fragments retained some functional activity, and could therefore, together with other determinants, contribute to modulate the disease phenotype. This new founder mutation, the most frequent mutation described in European populations so far, and these unusual intronic mutations, widen the clinical and molecular spectrum of NS and offer new diagnostic perspectives for NS patients. PMID- 22089836 TI - Tree that provides paclitaxel is put on list of endangered species. PMID- 22089834 TI - Automatic segmentation of ground-glass opacities in lung CT images by using Markov random field-based algorithms. AB - Chest radiologists rely on the segmentation and quantificational analysis of ground-glass opacities (GGO) to perform imaging diagnoses that evaluate the disease severity or recovery stages of diffuse parenchymal lung diseases. However, it is computationally difficult to segment and analyze patterns of GGO while compared with other lung diseases, since GGO usually do not have clear boundaries. In this paper, we present a new approach which automatically segments GGO in lung computed tomography (CT) images using algorithms derived from Markov random field theory. Further, we systematically evaluate the performance of the algorithms in segmenting GGO in lung CT images under different situations. CT image studies from 41 patients with diffuse lung diseases were enrolled in this research. The local distributions were modeled with both simple and adaptive (AMAP) models of maximum a posteriori (MAP). For best segmentation, we used the simulated annealing algorithm with a Gibbs sampler to solve the combinatorial optimization problem of MAP estimators, and we applied a knowledge-guided strategy to reduce false positive regions. We achieved AMAP-based GGO segmentation results of 86.94%, 94.33%, and 94.06% in average sensitivity, specificity, and accuracy, respectively, and we evaluated the performance using radiologists' subjective evaluation and quantificational analysis and diagnosis. We also compared the results of AMAP-based GGO segmentation with those of support vector machine-based methods, and we discuss the reliability and other issues of AMAP-based GGO segmentation. Our research results demonstrate the acceptability and usefulness of AMAP-based GGO segmentation for assisting radiologists in detecting GGO in high-resolution CT diagnostic procedures. PMID- 22089837 TI - Breast cancer: overview & updates. AB - Breast cancer is a complex disease and treatment recommendations are continually changing. It is the leading cancer in women and the second leading cause of cancer mortality. This overview of breast cancer will discuss pathologic features, local and systemic treatment considerations, endocrine therapy, metastatic treatment regimens, and follow-up for optimal breast health. Recent approvals that advance the treatment of metastatic breast cancer are also addressed. PMID- 22089838 TI - Cellular regulation of the inflammatory response. AB - In simple terms, inflammation can be defined as a beneficial, nonspecific response of tissues to injury that generally leads to restoration of normal structure and function. In this concept, resolution of the inflammatory response, once it has achieved its protective and pro-immunogenic functions, becomes a critical determinant of what might be considered the paradox of inflammation. On one hand, inflammation is essential to resolve tissue injury and maintain homeostasis. On the other, inflammation is a key participant in the great majority of human diseases. Accordingly, to achieve complete resolution of inflammation, it is necessary to both turn off inflammatory mediator production and inflammatory cell accumulation and to remove inflammatory cells and debris without initiating an autoimmune response. Much of this process involves key activities of the mononuclear phagocyte series of cells, including resident and recruited macrophages. Recognition of activated and dying acute inflammatory cells by mononuclear phagocytes has been shown to (a) enhance macropinocytic activity for removal of debris, (b) enhance uptake of the effete inflammatory cells themselves, (c) induce inflammosuppressive and immunosuppressive mediators such as TGFbeta and IL-10 that can down-regulate and limit proinflammatory mediator production, and (d) induce production of growth factors for tissue cells that may play key roles in tissue repair. Defects in these highly regulated processes are associated with persistent inflammation and/or autoimmunity in overaggressive resolution mechanisms such as nonresolving fibrosis or persistent tissue destruction as in emphysema. PMID- 22089839 TI - Proceedings of the 2011 National Toxicology Program Satellite Symposium. AB - The 2011 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Denver, Colorado in advance of the Society of Toxicologic Pathology's 30th Annual Meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include: proliferative lesions from various fish species including ameloblastoma, gas gland hyperplasia, nodular regenerative hepatocellular hyperplasia, and malignant granulosa cell tumor; spontaneous cystic hyperplasia in the stomach of CD1 mice and histiocytic aggregates in the duodenal villous tips of treated mice; an olfactory neuroblastoma in a cynomolgus monkey; various rodent skin lesions, including follicular parakeratotic hyperkeratosis, adnexal degeneration, and epithelial intracytoplasmic accumulations; oligodendroglioma and microgliomas in rats; a diagnostically challenging microcytic, hypochromic, responsive anemia in rats; a review of microcytes and microcytosis; nasal lesions associated with green tea extract and Ginkgo biloba in rats; corneal dystrophy in Dutch belted rabbits; valvulopathy in rats; and lymphoproliferative disease in a cynomolgus monkey. PMID- 22089840 TI - TCDD: an environmental immunotoxicant reveals a novel pathway of immunoregulation -a 30-year odyssey. AB - I was honored to be the keynote speaker at the 30th Annual Society of Toxicologic Pathology Symposium "Toxicologic Pathology and the Immune System." I had the opportunity to reminisce about events in the 1970s that set the stage for the birth and subsequent growth of the field of immunotoxicology and to summarize my research career that has spanned the past 40 years as well. An initial focus on the immunotoxicity of pentachlorophenol led my laboratory into the aryl hydrocarbon receptor (AHR) field and the study of its most potent ligand, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). My research career has been devoted to trying to elucidate the immunological basis of TCDD's profound immunosuppressive activity that is mediated by activation of AHR. In recent years, my laboratory has focused on the role of CD4(+ )T cells as targets of TCDD, and we were the first to describe the induction of AHR-dependent regulatory T cells (Tregs). The ability to induce Tregs using an exogenous AHR ligand to activate the AHR-Treg pathway represents a novel approach to the prevention and/or treatment of autoimmune disease. We are currently searching for such ligands. PMID- 22089841 TI - Potentially increased sensitivity of pregnant and lactating female rats to immunotoxic agents. AB - Characteristic susceptibility to environmental and pharmaceutical exposure may occur during periods in life of marked histophysiological changes of the immune system. Perinatal development is such a period; pregnancy followed by lactation is potentially another one. Here, we explored the influence of pregnancy and lactation on the model immunotoxic compound di-n-octyltin dichloride (DOTC) in rats using clinical and histopathological parameters. Female rats were exposed to 0, 3, 10, or 30 mg DOTC/kg feed during pregnancy and up to 20 (at weaning) or 56 days after delivery. Age-matched nonmated females were exposed during the same time periods. DOTC at the level of 10 and 30 mg/kg decreased thymus weight and affected thymus morphology in the lactating rats. In addition, DOTC decreased the numbers of neutrophils in the lactating rats. These effects were no longer apparent at day 56 despite continuous exposure to DOTC. This explorative study indicates that the innate and adaptive immune system may be especially sensitive to immunotoxicants during pregnancy and lactation. PMID- 22089842 TI - Immune functioning in non lymphoid organs: the liver. AB - The liver is the primary hematopoietic organ of the mammalian body during the fetal stage. The postnatal liver retains immunologically important functions and contains a substantial population of immunologically active cells, including T and B lymphocytes, Kupffer cells, liver-adapted natural killer (NK) cells (pit cells), natural killer cells expressing T cell receptor (NKT cells), stellate cells, and dendritic cells. The liver is the major site of production of the acute phase proteins that are associated with acute inflammatory reactions. Kupffer cells have an important role in the nonspecific phagocytosis that comprises a major component of the barrier to invasion of pathogenic organisms from the intestine. Hepatic NK and NKT cells are important in the nonspecific cell killing that is important in resistance to tumor cell invasion. The liver has a major role in deletion of activated T cells and induction of tolerance to ingested and self-antigens. Disposal of waste molecules generated through inflammatory, immunologic, or general homeostatic processes is accomplished via the action of specific endocytic receptors on sinusoidal endothelial cells of the liver. Age-related changes in sinusoids (pseudocapillarization), autophagy, and functions of various hepatic cell populations result in substantial alterations in many of these immunologically important functions. PMID- 22089843 TI - Enhanced histopathology of the immune system: a review and update. AB - Enhanced histopathology (EH) of the immune system is a tool that the pathologist can use to assist in the detection of lymphoid organ lesions when evaluating a suspected immunomodulatory test article within a subchronic study or as a component of a more comprehensive, tiered approach to immunotoxicity testing. There are three primary points to consider when performing EH: (1) each lymphoid organ has separate compartments that support specific immune functions; (2) these compartments should be evaluated individually; and (3) semiquantitative descriptive rather than interpretive terminology should be used to characterize any changes. Enhanced histopathology is a screening tool that should be used in conjunction with study data including clinical signs, gross changes, body weight, spleen and thymus weights, other organ or tissue changes, and clinical pathology. Points to consider include appropriate tissue collection, sectioning, and staining; lesion grading; and diligent comparison with concurrent controls. The value of EH of lymphoid organs is to aid in the identification of target cell type, changes in cell production and cell death, changes in cellular trafficking and recirculation, and determination of mechanism of action. PMID- 22089844 TI - General session 3: acquired immunity. AB - Session 3 of the Toxicologic Pathology and the Immune System Symposium, presented as part of the 30th Annual Symposium of the Society of Toxicologic Pathology in 2011, focused on the biological advances in control of selected cellular and secretory components of acquired immunity. Acquired immunity goes beyond innate immunity to provide controlled recognition and memory for specific antigenic challenges. Predominately involving activation of T and B lymphocytes, the resulting cellular- and secretory-mediated activity provides immediate and long term host defenses to antigenic challenge. This session highlighted the biological advances in function and dysfunction of acquired immunity through regulatory T cells, the pathophysiology of effector cells and secretory molecules in immunosuppression, allergic inflammatory disease, and dysregulation that leads to loss of tolerance and autoimmune disease. A brief overview of major concepts in acquired immunity and summaries of the above themes are covered herein, and discussions of these themes are covered in greater detail in this issue of Toxicologic Pathology. PMID- 22089845 TI - Building a successful trauma practice in a community setting. AB - The development of a busy community-based trauma practice is a multifaceted endeavor that requires good clinical judgment, business acumen, interpersonal skills, and negotiation tactics. Private practice is a world in which perfect outcomes are expected and efficiency is paramount. Successful operative outcomes are dependent on solid clinical training, good preoperative planning, and communication with mentors when necessary. Private practitioners must display confidence, polite behavior, and promptness. Maintaining availability for consultation from emergency room physicians, private practice physicians, and local orthopaedic surgeons is a powerful marketing tool. Orthopaedic trauma surgery has been shown to be a profitable field for hospitals and private practitioners. However, physician success depends on a sound understanding of hospital finance, marketing skills, and knowledge of billing and coding. As the financial pressures of medical care increase, hospital negotiation will be paramount, and private practitioners must combine clinical and business skills to provide good patient care while maintaining independence and financial security. PMID- 22089846 TI - Building a successful trauma practice in academics. AB - Building a successful trauma practice in the academic medicine sector requires planning, contemplation, and continuous reevaluation. Although there are no rigid formulas, there are some common sense approaches that can help you start along the path toward a successful academic trauma career. This article outlines a blueprint that I have found helpful in establishing my academic practice. There are 4 major areas of emphasis that we will discuss: (1) the importance of a definable career path and goals; (2) developing a small understanding of the business aspects of medicine and trauma; (3) the value of developing a niche within the practice of trauma; and (4) The importance of developing complementary orthopaedic skills outside the realm of conventional trauma. Occasionally, the third and fourth areas may overlap. PMID- 22089847 TI - Finding your first job in a community hospital. AB - Community hospitals offer excellent opportunities for graduating orthopaedic trauma fellows. To successfully compete for these jobs, applicants today must be better prepared than their predecessors. Organizing your practice aspirations and researching job opportunities before the interview are necessary for an effective job search. Often, a collaborative effort with hospital administrators is required to establish a viable practice that fulfills the unique needs of the hospital and surrounding community while concurrently satisfying your practice goals. Issues to consider in defining your desired practice, guidelines on how to prepare for an interview with a community hospital, and suggestions on how to justify the expense of establishing your practice are presented. PMID- 22089848 TI - Finding your first job in academics: interviewing strategies. AB - Successfully obtaining your first academic orthopaedic surgery position is a daunting adventure, but one in which you can succeed with proper preparation. First, you must identify specifically what you want to be doing on a daily basis at work. Then, you find places where you can potentially do those things. The interview will provide more definitive information and will allow you to assess if you can happily work in that environment. Remember that you must have balance in your life, so consider if the area is suitable to your and to your family's needs. By identifying your personal goals and desires of this initial position and thoroughly preparing for the entire interview process, you will be able to locate the most desirable opportunity available. PMID- 22089849 TI - Intramedullary nailing: evolutions of femoral intramedullary nailing: first to fourth generations. AB - Intramedullary femoral nailing is the gold standard for femoral shaft fixation but only in the past 27 years. This rapid replacement of closed traction and cast techniques in North America was a controversial and contentious evolution in surgery. As we enter the fourth generation of implant design, capabilities, and surgical technique, it is important to understand the driving forces for this technology. These forces included changes in radiographic imaging capabilities, biomaterial design and computer-assisted manufacturing, and the recognition of the importance of mobilization of the trauma patient to avoid systemic complications and optimize functional recovery. PMID- 22089850 TI - Introduction: Young practitioners forum supplement. PMID- 22089851 TI - My first year in academic practice: what I learned, what I wish I knew, what I would do differently. AB - Joining a practice for the first time after training, whether in academia or the private sector, is fraught with challenges and a learning curve. Postgraduate education has not sufficiently taught anyone how to manage the nuances of this new arena or how to become successful. Success is not solely a function measured by reportable taxable income. Respect by colleagues, patients, partners, and staff is just as important, if not more so. The financial attributes will be realized if the tangibles and intangibles discussed are appropriately executed in the correct environment. This article will discuss what to be cognizant of during the first years in academic practice and how to build a foundation for success. PMID- 22089852 TI - Navigating the orthopaedic trauma fellowship match from a candidate's perspective. AB - The Orthopaedic Trauma Fellowship Match is now in its fourth year as the principal match service for prospective orthopaedic traumatology fellowship candidates. The match is facilitated by SF Match. There are now more than 50 participating programs in the United States and Canada, and the number of applicants has expanded in recent years. For many applicants, the match process can be very time consuming and expensive and there are a multitude of factors to consider. Here, we share our experiences in the trauma match and offer our best advice for success. PMID- 22089853 TI - Research in a non-academic setting: it can be done. AB - The need for quality research to promote evidence-based practice and optimize patient care is well recognized. This is particularly relevant in orthopedic trauma care, as trauma is a leading cause of morbidity and mortality worldwide. Across the spectrum of academic, clinical, and health care administration physician roles, research remains fundamental to bridging theory, practice, and education. A gap exists, however, between research and practice, especially for those physicians practicing outside traditional academic centers. Orthopedic trauma surgeons are well situated to contribute to important research; however the majority of those in practice at non-academic centers do not have a significant research component structured into their physician role. In this article, the authors outline the importance of orthopedic trauma surgeons outside of academic centers being engaged in research and present some advice on how to effectively participate in these endeavors. In this setting, orthopedic trauma research involvement includes asking researchable questions, being a savvy manager of research collaborators, staff, and funding, and finding one's own level of research involvement. PMID- 22089854 TI - Research: getting started in an academic setting. AB - Surgeons who choose a position in an academic teaching center have chosen to incorporate research and education into their clinical practice. These clinicians scientists need passion, an inquiring mind, pertinent questions, time, money, and a research team to pursue a lifetime of intellectual challenges and patient care. The desire and passion for research is a critical requirement. An "inquiring mind" has to have a relevant question that is feasible to be tested and attain an answer. Adequate time carved into one's weekly schedule will greatly facilitate research productivity. Pursuit of money will also assist in obtaining the support personnel to help gather data, communicate with institutional review boards, and write grants and manuscripts. All these components will be critical members of the "research team." Established teams can also greatly facilitate orthopaedic research by joining groups that are doing multicenter studies with established studies. This can be a great learning experience and introduction into multicenter research. PMID- 22089855 TI - Things you never thought of that make a difference: personal goals, common sense, and good behavior in practice. AB - There are many aspects of your practice that you never think of when you first get into your new practice environment. You have spent the better part of your life training in a rigorous surgical residency and possibly fellowship. You have worked hard to get to this station in life. Because of your training and the obvious fact that you are a hard-driving individual, there are certain subtleties to a successful practice that you might have overlooked or never thought about during your training years. In many ways, it is the "little things" that you never learned or never thought of that will affect your overall long-term practice success, personal happiness, and relationships the most. This article reviews aspects of practice that at first glance are merely good common sense. PMID- 22089856 TI - When things don't work out: finding another job. AB - It is extremely common for young orthopaedic surgeons find themselves in unsatisfactory practice situations early in their careers. This article highlights several points to bear in mind when considering a change of employment in the first few years of practice. Many factors should be revisited from the candidate's initial job search to fully analyze the situation. If the problems are found to be irreconcilable, then the decision can be made to find a more suitable setting, but the relocation process should be handled judiciously. There are many resources available that can be helpful to make a successful transition. PMID- 22089857 TI - Remodeling of the epitope repertoire of a candidate idiotype vaccine by targeting to lysosomal degradation in dendritic cells. AB - The generation of efficacious vaccines against self-antigens expressed in tumor cells requires breakage of tolerance, and the refocusing of immune responses toward epitopes for which tolerance may not be established. While the presentation of tumor antigens by mature dendritic cells (mDC) may surpass tolerance, broadening of the antigenic repertoire remains an issue. We report that fusion of the candidate idiotype vaccine IGKV3-20 to the Gly-Ala repeat (GAr) of the Epstein-Barr virus nuclear antigen (EBNA)-1 inhibits degradation by the proteasome and redirects processing to the lysosome. mDCs transduced with a recombinant lentivirus encoding the chimeric idiotype efficiently primed CD4+ and CD8+ cytotoxic T-cell (CTL) responses that lysed autologous blasts expressing IGKV3-20 or pulsed with IGKV3-20 synthetic peptides, and HLA-matched IGKV3-20 positive tumor cell lines. Comparison of the cytotoxic response of CD4+ and CD8+ T lymphocytes activated by mDCs expressing the wild-type or chimeric IGKV3-20 reveled largely non-overlapping epitope repertoires in both CD4+ and CD8+ effectors. Thus, fusion to the GAr may provide an effective means to broaden the immune response to an endogenous protein by promoting the presentation of antigenic epitopes that require a lysosome-dependent processing step. PMID- 22089858 TI - Iron-induced remodeling in cultured rat pulmonary artery endothelial cells. AB - Although iron is known to be a component of the pathogenesis and/or maintenance of acute lung injury (ALI) in experimental animals and human subjects, the majority of these studies have focused on disturbances in iron homeostasis in the airways resulting from exposure to noxious gases and particles. Considerably less is known about the effect of increased plasma levels of redox-reactive non transferrin bound iron (NTBI) and its impact on pulmonary endothelium. Plasma levels of NTBI can increase under various pathophysiological conditions, including those associated with ALI, and multiple mechanisms are in place to affect the [Fe(2+)]/[Fe(3+)] redox steady state. It is well accepted, however, that intracellular transport of NTBI occurs after reduction of [Fe(3+)] to [Fe(2+)] (and is mediated by divalent metal transporters). Accordingly, as an experimental model to investigate mechanisms mediating vascular effects of redox reactive iron, rat pulmonary artery endothelial cells (RPAECs) were subjected to pulse treatment (10 min) with [Fe(2+)] nitriloacetate (30 MUM) in the presence of pyrithione, an iron ionophore, to acutely increase intracellular labile pool of iron. Cellular iron influx and cell shape profile were monitored with time-lapse imaging techniques. Exposure of RPAECs to [Fe(2+)] resulted in: (i) an increase in intracellular iron as detected by the iron sensitive fluorophore, PhenGreen; (ii) depletion of cell glutathione; and (iii) nuclear translocation of stress response transcriptional factors Nrf2 and NFkB (p65). The resulting iron-induced cell alterations were characterized by cell polarization and formation of membrane cuplike and microvilli-like projections abundant with ICAM-1, caveolin 1, and F-actin. The iron-induced re-arrangements in cytoskeleton, alterations in focal cell-cell interactions, and cell buckling were accompanied by decrease in electrical resistance of RPAEC monolayer. These effects were partially eliminated in the presence of N,N'-bis (2-hydroxybenzyl) ethylenediamine-N,N'-diacetic acid, an iron chelator, and Y27632, a Rho-kinase inhibitor. Thus acute increases in labile iron in cultured pulmonary endothelium result in structural remodeling (and a proinflammatory phenotype) that occurs via post-transcriptional mechanisms regulated in a redox sensitive fashion. PMID- 22089859 TI - The copper-inducible ComR (YcfQ) repressor regulates expression of ComC (YcfR), which affects copper permeability of the outer membrane of Escherichia coli. AB - The pathway of copper entry into Escherichia coli is still unknown. In an attempt to shed light on this process, a lux-based biosensor was utilized to monitor intracellular copper levels in situ. From a transposon-mutagenized library, strains were selected in which copper entry into cells was reduced, apparent as clones with reduced luminescence when grown in the presence of copper (low glowers). One low-glower had a transposon insertion in the comR gene, which encodes a TetR-like transcriptional regulator. The mutant strain could be complemented by the comR gene on a plasmid, restoring luminescence to wild-type levels. ComR did not regulate its own expression, but was required for copper induction of the neighboring, divergently transcribed comC gene, as shown by real time quantitative PCR and with a promoter-lux fusion. The purified ComR regulator bound to the promoter region of the comC gene in vitro and was released by copper. By membrane fractionation, ComC was shown to be localized in the outer membrane. When grown in the presence of copper, ?comC cells had higher periplasmic and cytoplasmic copper levels, compared to the wild-type, as assessed by the activation of the periplasmic CusRS sensor and the cytoplasmic CueR sensor, respectively. Thus, ComC is an outer membrane protein which lowers the permeability of the outer membrane to copper. The expression of ComC is controlled by ComR, a novel, TetR-like copper-responsive repressor. PMID- 22089860 TI - Combination of branched-chain amino acid and angiotensin-converting enzyme inhibitor improves liver fibrosis progression in patients with cirrhosis. AB - An effective therapeutic strategy for suppressing liver fibrosis should improve the overall prognosis of patients with chronic liver diseases. Although enormous efforts are ongoing to develop anti-fibrotic agents, no drugs have yet been approved as anti-fibrotic agents for humans. Insulin resistance (IR) is reportedly involved in the progression of liver fibrosis. The aim of the present study was to evaluate the effect of combination treatment with a clinically used branched-chain amino acid (BCAA) and an angiotensin-converting enzyme inhibitor (ACE-I) on several fibrotic indices in patients with liver cirrhosis under the condition of IR. BCAA granules (Livact; 12 g/day) and/or ACE-I (perindopril; 4 mg/day) were administered, and several indices were analyzed. A 48-month follow up revealed that the combination treatment with BCAA and ACE-I markedly improved the progression of serum fibrosis markers, whereas single treatment with either BCAA or ACE-I did not exert these inhibitory effects. The plasma level of transforming growth factor-beta was significantly attenuated almost in parallel with the suppression of serum fibrosis markers. Furthermore, the combined treatment with BCAA and ACE-I improved the serum albumin level and IR, which was evaluated using the homeostasis model assessment method for IR. Taken together, since both BCAA and ACE-I are widely used with safety in clinical practice, these results indicate that this combination therapy may represent a potential new future strategy against liver fibrosis development in patients with liver cirrhosis under the condition of IR. PMID- 22089861 TI - Experimental and theoretical investigations of isomerization reactions of ionized acetone and its dimer. AB - Ionization dynamics of acetone and its dimer in supersonic jets is investigated by a combination of experimental and theoretical techniques, both of which have recently been developed. In experiments, the neutral and the cationic structures are explored by infrared predissociation spectroscopy with the vacuum-ultraviolet photoionization detection schemes. Reaction paths following the one-photon ionization of the acetone monomer and its dimer have been studied by the joint use of several theoretical methods including the ab initio molecular dynamics, the global reaction route mapping, the intrinsic reaction coordinate, and the artificial force induced reaction calculations. Upon one-photon ionization, the dimer isomerizes to the H-bonded form, in which the enol cation of acetone is bound to the neutral molecule, while this enolization is energetically forbidden in the acetone monomer. The enolization of the dimer cation occurs through a two step proton-transfer from the methyl group of the ionized moiety, and is catalyzed by the neutral moiety within the dimer cation. PMID- 22089862 TI - One-pot synthesis of novel 2,3-dihydro-1H-indazoles. AB - A copper(I)-mediated one-pot synthesis of 2,3-dihydro-1H-indazole heterocycles has been developed. This synthetic route provides the desired indazoles in moderate to good yields (55%-72%) which are substantially better than those achievable with an alternative two-step reaction sequence. The reaction is tolerant of functionality on the aromatic ring. PMID- 22089863 TI - Mn(III)-initiated facile oxygenation of heterocyclic 1,3-dicarbonyl compounds. AB - The Mn(III)-initiated aerobic oxidation of heterocyclic 1,3-dicarbonyl compounds, such as 4-alkyl-1,2-diphenylpyrazolidine-3,5-diones, 1,3-dialkylpyrrolidine-2,4 diones, 3-alkyl-1,5-dimethylbarbituric acids, and 3-butyl-4-hydroxy-2-quinolinone gave excellent to good yields of the corresponding hydroperoxides, which were gradually degraded by exposure to the metal initiator after the reaction to afford the corresponding alcohols. The synthesis of 30 heterocyclic 1,3 dicarbonyl compounds, the corresponding hydroperoxides and the 10 alcohols, their characterization, and the limitations of the procedure are described. In addition, the mechanism of the hydroperoxidation and the redox decomposition of the hydroperoxides are discussed. PMID- 22089864 TI - The beneficial effect of hydrogen on CO oxidation over Au catalysts. A computational study. AB - Density functional theory calculations have been carried out to explore the effect of hydrogen on the oxidation of CO in relation to the preferential oxidation of CO in the presence of excess hydrogen (PROX). A range of gold surfaces have been selected including the (100), stepped (310) surfaces and diatomic rows on the (100) surface. These diatomic rows on Au(100) are very efficient in H-H bond scission. O(2) hydrogenation strongly enhances the surface oxygen interaction and assists in scission of the O-O bond. The activation energy required to make the reaction intermediate hydroperoxy (OOH) from O(2) and H is small. However, we postulate its presence on our Au models as the result of diffusion from oxide supports to the gold surfaces. The OOH on Au in turn opens many low energy cost channels to produce H(2)O and CO(2). CO is selectively oxidized in a H(2) atmosphere due to the more favorable reaction barriers while the formation of adsorbed hydroperoxy enhances the reaction rate. PMID- 22089866 TI - Coexistence of predator and prey in intraguild predation systems with ontogenetic niche shifts. AB - In basic intraguild predation (IGP) systems, predators and prey also compete for a shared resource. Theory predicts that persistence of these systems is possible when intraguild prey is superior in competition and productivity is not too high. IGP often results from ontogenetic niche shifts, in which the diet of intraguild predators changes as a result of growth in body size (life-history omnivory). As a juvenile, a life-history omnivore competes with the species that becomes its prey later in life. Competition can hence limit growth of young predators, while adult predators can suppress consumers and therewith neutralize negative effects of competition. We formulate and analyze a stage-structured model that captures both basic IGP and life-history omnivory. The model predicts increasing coexistence of predators and consumers when resource use of stage-structured predators becomes more stage specific. This coexistence depends on adult predators requiring consumer biomass for reproduction and is less likely when consumers outcompete juvenile predators, in contrast to basic IGP. Therefore, coexistence occurs when predation structures the community and competition is negligible. Consequently, equilibrium patterns over productivity resemble those of three-species food chains. Life-history omnivory thus provides a mechanism that allows intraguild predators and prey to coexist over a wide range of resource productivity. PMID- 22089865 TI - A unified model of autopolyploid establishment and evolution. AB - The prevalence of polyploidy among flowering plants is surprising given the hurdles impeding the establishment and persistence of novel polyploid lineages. In the absence of strong assortative mating, reproductive assurance, or large intrinsic fitness advantages, new polyploid lineages face almost certain extinction through minority cytotype exclusion. Consequently, much work has focused on a search for adaptive advantages associated with polyploidy such as increased competitive ability, enhanced ecological tolerances, and increased resistance to pathogens. Yet, no consistent adaptive advantages of polyploidy have been identified. Here, to investigate the potential for autopolyploid establishment and persistence in the absence of any intrinsic fitness advantages, we develop a simulation model of a diploid population that sporadically gives rise to novel autopolyploids. The autopolyploids have only very small levels of initial assortative mating or niche differentiation, generated entirely by dosage effects of genome duplication, and they have realistic levels of reproductive assurance. Our results show that by allowing assortative mating and competitive interactions to evolve, establishment of novel autopolyploid lineages becomes common. Additional scenarios where adaptive optima change over time reveal that rapid environmental change promotes the replacement of diploid lineages by their autopolyploid descendants. These results help to explain recent empirical findings that suggest that many contemporary polyploid lineages arose during the Cretaceous-Tertiary extinction, without invoking adaptive advantages of polyploidy. PMID- 22089867 TI - The population and evolutionary dynamics of Vibrio cholerae and its bacteriophage: conditions for maintaining phage-limited communities. AB - Although bacteriophage have been reported to be the most abundant organisms on earth, little is known about their contribution to the ecology of natural communities of their host bacteria. Most importantly, what role do these viral parasitoids play in regulating the densities of bacterial populations? To address this question, we use experimental communities of Vibrio cholerae and its phage in continuous culture, and we use mathematical models to explore the population dynamic and evolutionary conditions under which phage, rather than resources, will limit the densities of these bacteria. The results of our experiments indicate that single species of bacterial viruses cannot maintain the density of V. cholerae populations at levels much lower than that anticipated on the basis of resources alone. On the other hand, as few as two species of phage can maintain these bacteria at densities more than two orders of magnitude lower than the densities of the corresponding phage-free controls for extensive periods. Using mathematical models and short-term experiments, we explore the population dynamic processes responsible for these results. We discuss the implications of this experimental and theoretical study for the population and evolutionary dynamics of natural populations of bacteria and phage. PMID- 22089868 TI - Sexual selection and conflict as engines of ecological diversification. AB - Ecological diversification presents an enduring puzzle: how do novel ecological strategies evolve in organisms that are already adapted to their ecological niche? Most attempts to answer this question posit a primary role for genetic drift, which could carry populations through or around fitness "valleys" representing maladaptive intermediate phenotypes between alternative niches. Sexual selection and conflict are thought to play an ancillary role by initiating reproductive isolation and thereby facilitating divergence in ecological traits through genetic drift or local adaptation. Here, I synthesize theory and evidence suggesting that sexual selection and conflict could play a more central role in the evolution and diversification of ecological strategies through the co optation of sexual traits for viability-related functions. This hypothesis rests on three main premises, all of which are supported by theory and consistent with the available evidence. First, sexual selection and conflict often act at cross purposes to viability selection, thereby displacing populations from the local viability optimum. Second, sexual traits can serve as preadaptations for novel viability-related functions. Third, ancestrally sex-limited sexual traits can be transferred between sexes. Consequently, by allowing populations to explore a broad phenotypic space around the current viability optimum, sexual selection and conflict could act as powerful drivers of ecological adaptation and diversification. PMID- 22089869 TI - A manipulative test of competing theories for metabolic scaling. AB - The reasons why metabolic rate (B) scales allometrically with body mass (M) remain hotly debated. The field is dominated by correlational analyses of the relationship between B and M; these struggle to disentangle competing explanations because both B and M are confounded with ontogeny, life history, and ecology. Here, we overcome these problems by using an experimental approach to test among competing metabolic theories. We examined the scaling of B in size manipulated and intact colonies of a bryozoan and show that B scales with M(0.5). To explain this, we apply a general model based on the dynamic energy budget theory for metabolic organization that predicts B on the basis of energy allocation to assimilation, maintenance, growth, and maturation. Uniquely, this model predicts the absolute value of B, emphasizes that there is no single scaling exponent of B, and demonstrates that a single model can explain the variation in B seen in nature. PMID- 22089870 TI - Using time series analysis to characterize evolutionary and plastic responses to environmental change: a case study of a shift toward earlier migration date in sockeye salmon. AB - Environmental change can shift the phenotype of an organism through either evolutionary or nongenetic processes. Despite abundant evidence of phenotypic change in response to recent climate change, we typically lack sufficient genetic data to identify the role of evolution. We present a method of using phenotypic data to characterize the hypothesized role of natural selection and environmentally driven phenotypic shifts (plasticity). We modeled historical selection and environmental predictors of interannual variation in mean population phenotype using a multivariate state-space model framework. Through model comparisons, we assessed the extent to which an estimated selection differential explained observed variation better than environmental factors alone. We applied the method to a 60-year trend toward earlier migration in Columbia River sockeye salmon Oncorhynchus nerka, producing estimates of annual selection differentials, average realized heritability, and relative cumulative effects of selection and plasticity. We found that an evolutionary response to thermal selection was capable of explaining up to two-thirds of the phenotypic trend. Adaptive plastic responses to June river flow explain most of the remainder. This method is applicable to other populations with time series data if selection differentials are available or can be reconstructed. This method thus augments our toolbox for predicting responses to environmental change. PMID- 22089871 TI - A comparison of dynamic-state-dependent models of the trade-off between growth, damage, and reproduction. AB - Fast growth can be costly, so trade-offs between growth and fitness are to be predicted when organisms adjust their growth to compensate for earlier environmental conditions. We developed four generic models of increasing complexity with different processes to predict the indeterminate growth of vertebrate ectotherms, which is sensitive to ambient temperature even when food is not limiting. We contrast the predictions of the models with observed experimental data on growth trajectories, feeding activity, and reproductive investment of three-spined sticklebacks and inferred patterns of accumulation of biomolecular damage arising from activity and growth. All models predicted observed patterns of compensatory growth (both accelerating and decelerating) in response to earlier temperature perturbations, but the more complex models provided the best fit to experimental data. Growth trajectories influenced future reproductive investment regardless of final body size at breeding. Our findings suggest that while models with fewer parameters can predict basic patterns of growth in stable conditions, they cannot capture the costly long-term effects of deviations from steady growth trajectories. In contrast, models in which foraging activity is assumed to carry costs are capable of predicting the complex patterns of feeding, growth, and reproductive investment seen in animals, with the cost of a heightened mortality risk (e.g., through predation) being more important than the cost of increased physiological damage. PMID- 22089872 TI - Communal defense of territories and the evolution of sociality. AB - The evolution of group living has attracted considerable attention from behavioral ecologists working on a wide range of study species. However, theoretical research in this field has been largely focused on cooperative breeders. We extend this line of work to species that lack alloparental care (hereafter termed "noncooperative species") but that may benefit from grouping by jointly defending a common territory. We adopt a demographically explicit approach in which the rates of births and deaths as well as the dispersal decisions of individuals in the population determine the turnover rates of territories and the competition for breeding vacancies thus arising. Our results reveal that some of the factors thought to affect the evolution of cooperative breeding also affect the evolution of group living in noncooperative species. Specifically, high fecundity and low mortality of resident individuals both increase the degree of habitat saturation and make joining an established group more profitable for nonresidents (floaters). Moreover, if floaters can forcefully take over territories, the degree of habitat saturation also affects the chance that residents become targets of takeovers. In this situation, communal defense of territories becomes an important benefit that further promotes the evolution of group living. PMID- 22089873 TI - How does life adapt to a gravitational environment? The outline of the terrestrial gastropod shell. AB - How do several characteristics adapt to gravity while mutually influencing each other? Our study addresses this issue by focusing on the terrestrial gastropod shell. The geometric relationship between the spire index (shell height/diameter) and outline (cylindricality) is theoretically estimated. When the shell grows isometrically, a high-spired shell becomes conical in shape and a low-spired shell becomes cylindrical in shape. A physical model shows that the lowest- and highest-spired shells are the most balanced. In addition, a cone shape is the most balanced for a low-spired shell, and a column shape is the most balanced for a high-spired shell. Spire index and cylindricality measured for freshwater gastropods follow the relationship estimated by the model, whereas those for terrestrial gastropods deviate from this relationship. This translates to a high shell being more cylindrical than a flat shell, except in the case of extremely high or low shells. This suggests that the shape of the most balanced shells (lowest and highest shell heights) is constrained by coiling geometry but that relatively unbalanced shells (intermediate shell heights) do not follow a coiling geometry, as a result of adaptation to enable the snail to carry its shell more effectively. PMID- 22089874 TI - The role of predators in maintaining the geographic organization of aposematic signals. AB - Selective predation of aposematic signals is expected to promote phenotypic uniformity. But while these signals may be uniform within a population, numerous species display impressive variations in warning signals among adjacent populations. Predators from different localities who learn to avoid distinct signals while performing intense selection on others are thus expected to maintain such a geographic organization. We tested this assumption by placing clay frog models, representing distinct color morphs of the Peruvian poison dart frog Ranitomeya imitator and a nonconspicuous frog, reciprocally between adjacent localities. In each locality, avian predators were able to discriminate between warning signals; the adjacent exotic morph experienced up to four times more attacks than the local one and two times more than the nonconspicuous phenotype. Moreover, predation attempts on the exotic morph quickly decreased to almost nil, suggesting rapid learning. This experiment offers direct evidence for the existence of different predator communities performing localized homogenizing selection on distinct aposematic signals. PMID- 22089877 TI - Understanding shifts in wildfire regimes as emergent threshold phenomena. AB - Ecosystems driven by wildfire regimes are characterized by fire size distributions resembling power laws. Existing models produce power laws, but their predicted exponents are too high and fail to capture the exponent's variation with geographic region. Here we present a minimal model of fire dynamics that describes fire spread as a stochastic birth-death process, analogous to stochastic population growth or disease spread and incorporating memory effects from previous fires. The model reproduces multiple regional patterns in fire regimes and allows us to classify different regions in terms of their proximity to a critical threshold. Transitions across this critical threshold imply abrupt and pronounced increases in average fire size. The model predicts that large regions in Canada are currently close to this transition and might be driven beyond the threshold in the future. We illustrate this point by analyzing the time series for large fires (>199 ha) from the Canadian Boreal Plains, found to have shifted from a subcritical regime to a critical regime in the recent past. By contrast to its predecessor, the model also suggests that a critical transition, and not self-organized criticality, underlies forest fire dynamics, with implications for other ecological systems exhibiting power-law like patterns, in particular for their sensitivity to environmental change and control efforts. PMID- 22089878 TI - The evolution of bacteriocin production in bacterial biofilms. AB - Bacteriocin production is a spiteful behavior of bacteria that is central to the competitive dynamics of many human pathogens. Social evolution predicts that bacteriocin production is favored when bacteriocin-producing cells are mixed at intermediate frequency with their competitors and when competitive neighborhoods are localized. Both predictions are supported by biofilm experiments. However, the means by which physical and biological processes interact to produce conditions that favor the evolution of bacteriocin production remain to be investigated. Here we fill this gap using analytical and computational approaches. We identify and collapse key parameters into a single number, the critical bacteriocin range, that measures the threshold distance from a focal bacteriocin-producing cell within which its fitness is higher than that of a sensitive cell. We develop an agent-based model to test our predictions and confirm that bacteriocin production is most favored when relatedness is intermediate and competition is local. We then use invasion analysis to determine evolutionarily stable strategies for bacteriocin production. Finally, we perform long-term evolutionary simulations to analyze how the critical bacteriocin range and genetic lineage segregation affect biodiversity in multistrain biofilms. We find that biodiversity is maintained in highly segregated biofilms for a wide array of critical bacteriocin ranges. However, under conditions of high nutrient penetration leading to well-mixed biofilms, biodiversity rapidly decreases and becomes sensitive to the critical bacteriocin range. PMID- 22089881 TI - Advanced fabrication of metal-organic frameworks: template-directed formation of polystyrene@ZIF-8 core-shell and hollow ZIF-8 microspheres. AB - The conjunction of porous ZIF-8 with polystyrene spheres is demonstrated to induce the formation of polystyrene@ZIF-8 core-shell structures. A subsequent etching process on polystyrene@ZIF-8 core-shells to remove polystyrene cores results in a unique hollow ZIF-8. PMID- 22089879 TI - Causes of variation in malaria infection dynamics: insights from theory and data. AB - Parasite strategies for exploiting host resources are key determinants of disease severity (i.e., virulence) and infectiousness (i.e., transmission between hosts). By iterating the development of theory and empirical tests, we investigated whether variation in parasite traits across two genetically distinct clones of the rodent malaria parasite, Plasmodium chabaudi, explains differences in within host infection dynamics and virulence. First, we experimentally tested key predictions of our earlier modeling work. As predicted, the more virulent genotype produced more progeny parasites per infected cell (burst size), but in contrast to predictions, invasion rates of red blood cells (RBCs) did not differ between the genotypes studied. Second, we further developed theory by confronting our earlier model with these new data, testing a new set of models that incorporate more biological realism, and developing novel theoretical tools for identifying differences between parasite genotypes. Overall, we found robust evidence that differences in burst sizes contribute to variation in dynamics and that differential interactions between parasites and host immune responses also play a role. In contrast to previous work, our model predicts that RBC age structure is not important for explaining dynamics. Integrating theory and empirical tests is a potentially powerful way of progressing understanding of disease biology. PMID- 22089882 TI - Structure-based prediction of protein-protein binding affinity with consideration of allosteric effect. AB - The conformational change upon protein-protein binding is largely ignored for a long time in the affinity prediction community. However, it is widely recognized that allosteric effect does play an important role in biomolecular recognition and association. In this article, we describe a new quantitative structure activity relationship (QSAR)-based strategy to capture the structural and nonbonding information relating to not only the direct noncovalent interactions between protein binding partners, but also the indirect allosteric effect associated with binding. This method is then employed to quantitatively model and predict the protein-protein binding affinities compiled in a recently published benchmark consisting of 144 functionally diverse protein complexes with their structures available in both bound and unbound states (Kastritis et al. Protein Sci 20:482-491, 2011). With incorporating genetic algorithm and partial least squares regression (GA-PLS) into this method, a significant linear relationship between structural information descriptors and experimentally measured affinities is readily emerged and, on this basis, detailed discussions of physicochemical properties and structural implications underlying protein binding process, as well as the contribution of allosteric effect to the binding are addressed. We also give an empirical estimation of the prediction limit r(pred)(2) = 0.80 for structure-based method used to determine protein-protein binding affinity. PMID- 22089883 TI - Expression of transglutaminase-2 isoforms in normal human tissues and cancer cell lines: dysregulation of alternative splicing in cancer. AB - The multiple enzymatic activities and functions of transglutaminase type 2 (TG2) may be attributed to alternative TG2 molecules produced by differential splicing of TG2 mRNA. Different RNA transcripts of the human TG2 gene (TGM2) have been identified, but the expression of TG2 multiple transcripts has never been systematically addressed. We have confirmed and rationalized the main TG2 variants and developed a screening assay for the detection of alternative splicing of TG2, based on real-time reverse-transcription PCR. We have quantified the multiple TG2 transcripts in a wide range of normal tissues and in cancer cell lines from four different sites of origin. Our data show a significant correlation in the expression of canonical and alternative TG2 isoforms in normal human tissue, but differences in alternative splicing of TG2 in cancer cell lines, suggesting that in cancer cells the alternative splicing of TG2 is a more active process. PMID- 22089884 TI - Expression of the bacterial heavy metal transporter MerC fused with a plant SNARE, SYP121, in Arabidopsis thaliana increases cadmium accumulation and tolerance. AB - The bacterial merC gene from the Tn21-encoded mer operon is a potential molecular tool for improving the efficiency of metal phytoremediation. Arabidopsis SNARE molecules, including SYP111, SYP121, and AtVAM3 (SYP22), were attached to the C terminus of MerC to target the protein to various organelles. The subcellular localization of transiently expressed GFP-fused MerC-SYP111, MerC-SYP121, and MerC-AtVAM3 was examined in Arabidopsis suspension-cultured cells. We found that GFP-MerC-SYP111 and GFP-MerC-SYP121 localized to the plasma membrane, whereas GFP AtVAM3 localized to the vacuolar membranes. These results demonstrate that SYP111/SYP121 and AtVAM3 target foreign molecules to the plasma membrane and vacuolar membrane, respectively. To enhance the efficiency and potential of plants to sequester and accumulate cadmium from contaminated sites, transgenic Arabidopsis plants expressing MerC, MerC-SYP111, MerC-SYP121, or MerC-AtVAM3 were generated. The transgenic plants that expressed MerC, MerC-SYP121, or MerC-AtVAM3 appeared to be normal, whereas the transgenic that expressed MerC-SYP111 exhibited severe growth defects. The transgenic plants expressing merC-SYP121 were more resistant to cadmium than the wild type and accumulated significantly more cadmium. Thus, the expression of MerC-SYP121 in the plant plasma membrane may provide an ecologically compatible approach for the phytoremediation of cadmium pollution. PMID- 22089885 TI - Sequential cognitive skills in emphysema patients following lung volume reduction surgery: a 2-year longitudinal study. AB - PURPOSE: This study compared visuomotor speed and cognitive flexibility in emphysema patients treated with either standard multidisciplinary medical therapy (MT) or lung volume reduction surgery (LVRS), followed over a 2-year period. METHODS: MT patients (n = 544) and 542 LVRS patients completed the Trail Making Test (TMT) Parts A and B prior to randomization (baseline). Testing was repeated at 1 and 2 years. RESULTS: There were no differences on scores for TMT Parts A and B between the LVRS and MT groups at baseline or at years 1 and 2. No significant difference between MT and LVRS was noted in terms of overall change in TMT Parts A and B over 2 years. The MT group had a significant improvement on TMT Part A at each followup time compared with baseline (P < .03) but the LVRS group did not. Both the MT and LVRS groups had a significant decline in performance (increase in time to completion) on TMT Part B when comparing year 1 with baseline (P < .0001). CONCLUSION: Emphysema patients who received LVRS or MT as treatment performed similarly on measures of visuomotor speed and flexibility at baseline and 1- and 2-year followup. Both groups showed improvement on visuomotor speed during the first year yet overall cognitive flexibility declined. By the second year neither group had any significant change from baseline. These findings suggest that improvement on visuomotor speed and flexibility, observed in a previous 6-month study of LVRS subjects, was not sustained at 1- and 2-year followup. PMID- 22089887 TI - Clinical characteristics of meningiomas assessed by 11C-methionine and 18F fluorodeoxyglucose positron-emission tomography. AB - The clinical course of meningioma varies from case to case, despite similar characteristics on magnetic resonance (MR) imaging. Functional imaging including (11)C-methionine and (18)F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) has been widely studied for noninvasive preoperative evaluation of brain tumors. However, few reports have examined correlations between meningiomas and findings on (11)C-methionine and FDG PET. The objective of this study was to clarify the relationship between tumor characteristics and (11)C-methionine and FDG uptake in meningiomas. For 68 meningiomas in 51 cases, (11)C-methionine uptake was evaluated by measuring both mean and maximum tumor/normal (T/N) ratio for the whole area of the tumors. FDG uptake in 44 of those meningiomas was also analyzed. Tumor size was measured volumetrically, and tumor-doubling time was estimated. Histopathological evaluation was performed in 19 surgical cases. Mean and maximum T/N ratios of (11)C-methionine PET were significantly higher in skull base lesions than in non-skull-base lesions. Correlations of mean and maximum T/N ratio of (11)C-methionine PET with tumor-doubling time, MIB-1 labeling index, microvessel density and World Health Organization grading were not significant. Mean T/N ratio of (11)C-methionine PET correlated significantly with tumor volume according to logarithm regression modeling (P < 0.0001, R = 0.544). However, mean and maximum T/N ratio of FDG-PET correlated with none of the tumor characteristics described above. These results suggest that (11)C-methionine uptake correlates with tumor volume, but not with tumor aggressiveness. PMID- 22089888 TI - Increased major bleeding risk in patients with kidney dysfunction receiving enoxaparin: a meta-analysis. AB - PURPOSE: The elimination half-life and consequently the accumulation of enoxaparin increase as glomerular filtration rate (GFR) decreases. A dose adjustment for patients with a GFR <30 ml/min is recommended and considered relatively safe. Our intention was to identify whether the use of enoxaparin is safe and to determine what impact an enoxaparin dose adjustment has on patients with a GFR <60 ml/min. METHODS: A PubMed search and meta-analysis of literature were performed. Studies were analyzed to compare enoxaparin versus other heparins/heparinoids and investigate enoxaparin at different stages of kidney dysfunction. Only controlled trials were considered, and the enoxaparin dose had to be specified. The clinical endpoint was defined as apparent major bleeding. RESULTS: Out of 1,027 publications, 20 studies met the criteria and were analyzed. Our meta-analysis shows that enoxaparin major bleeding complications at a GFR < 60 ml/min increase significantly, with a relative risk (RR) of 1.67 [95% confidence interval (CI) 1.12-2.50) compared with other anticoagulants (p = 0.01). RR for patients on enoxaparin therapy increases exponentially with each stage of chronic kidney disease (CKD stage 1-5) [RR = 0.585 x exp(0.524 x CKD)]. Despite dose adjustment, the major bleeding risk is still significantly increased in patients with a GFR < 60 ml/min versus those with a GFR > 60 ml/min. CONCLUSION: Only patients with a GFR > 60 ml/min can be safely treated with enoxaparin. PMID- 22089889 TI - A detailed study of the intramolecular hydroamination of N-(ortho-alkynyl)aryl-N' substituted trifluoroacetamidines and bromodifluoroacetamidines. AB - The intramolecular hydroamination of N-(ortho-alkynyl)aryl-N'-substituted trifluoroacetamidines and bromodifluoroacetamidines is studied in detail. When the substituents on the alkyne fragment are aryl and alkyl groups, 5-endo-dig cyclization occurs utilizing NaAuCl(4).2H(2)O as a catalyst, while 6-exo-dig cyclization proceeds in the presence of K(2)CO(3) as a base. Interestingly, the indole derivatives are afforded with good regioselectivity via a 5-endo-dig pathway catalyzed by Cu(OAc)(2) when ortho-ethynyl appears on the aryl substituent of the amidine. The electrophilic cyclization of the amidines also shows good regioselectivity under the I(2)/NaHCO(3) system. At the end, a facile cascade synthesis of fluorinated quinazolones is described via hydroamination/ozonolysis from the corresponding amidine. PMID- 22089891 TI - [Treatment of chronic pain. Selected interventional methods]. PMID- 22089892 TI - Is it worth offering cardiovascular disease prevention to the elderly? AB - The question whether prevention in the elderly or in the old is still worthwhile arises frequently in clinical practice. The life expectancy (LE) of elderly persons is often underestimated and ranges for a 65-year-old European person from 17 to 23 years and for an 80-year-old from 8 and 11 years. In the elderly patients with cardiovascular disease, preventive measures are of great benefit. Smoking cessation results in substantial gains in LE and is more effective than most other interventions. Lipid lowering with statins is cost effective and the intensity of low-density lipoprotein cholesterol lowering correlates with the risk reduction of cardiac events and stroke without increasing the risk of cancer. A quality-adjusted life year costs US $ 18,800, less than the costs of a nursing home for 1 year. Exercise training decreases cardiovascular events and improves quality of life. The benefits of the Mediterranean diet are based on a small randomized trial, which is supplemented by a large observational database. A reduction in all-cause, cardiovascular disease, and cancer mortality is highly likely. Blood pressure lowering reduces stroke and all-cause mortality above the age of 80; however, the target blood pressure should be around 150/80 mmHg or slightly lower. Annual vaccination against influenza is one of the most cost effective methods to prolong life and should not be forgotten in patients with cardiovascular disease above the age of 65. Thus a number of options are available to add quality-adjusted life years in the elderly by adhering to the general guidelines for cardiovascular prevention. PMID- 22089890 TI - [Emergency anesthesia, airway management and ventilation in major trauma. Background and key messages of the interdisciplinary S3 guidelines for major trauma patients]. AB - Patients with multiple trauma presenting with apnea or a gasping breathing pattern (respiratory rate <6/min) require prehospital endotracheal intubation (ETI) and ventilation. Additional indications are hypoxia (S(p)O(2)<90% despite oxygen insufflation and after exclusion of tension pneumothorax), severe traumatic brain injury [Glasgow Coma Scale (GCS)<9], trauma-associated hemodynamic instability [systolic blood pressure (SBP)<90 mmHg] and severe chest trauma with respiratory insufficiency (respiratory rate >29/min). The induction of anesthesia after preoxygenation is conducted as rapid sequence induction (analgesic, hypnotic drug, neuromuscular blocking agent). With the availability of ketamine as a viable alternative, the use of etomidate is not encouraged due to its side effects on adrenal function. An electrocardiogram (ECG), blood pressure measurement and pulse oximetry are needed to monitor the emergency anesthesia and the secured airway. Capnography is absolutely mandatory to confirm correct placement of the endotracheal tube and to monitor tube dislocations as well as ventilation and oxygenation in the prehospital and hospital setting. Because airway management is often complicated in trauma patients, alternative devices and a fiber-optic endoscope need to be available within the hospital. Use of these alternative measures for airway management and ventilation should be considered at the latest after a maximum of three unsuccessful intubation attempts. Emergency medical service (EMS) physicians should to be trained in emergency anesthesia, ETI and alternative methods of airway management on a regular basis. Within hospitals ETI, emergency anesthesia and ventilation are to be conducted by trained and experienced anesthesiologists. When a difficult airway or induction of anesthesia is expected, endotracheal intubation should be supervised or conducted by an anesthesiologist. Normoventilation should be the goal of mechanical ventilation. After arrival in the resuscitation room the ventilation will be controlled and guided with the help of arterial blood gas analyses. After temporary removal of a cervical collar, the cervical spine needs to be immobilized by means of manual in-line stabilization when securing the airway. PMID- 22089893 TI - Gun utopias? Firearm access and ownership in Israel and Switzerland. AB - The 2011 attempted assassination of a US representative renewed the national gun control debate. Gun advocates claim mass-casualty events are mitigated and deterred with three policies: (a) permissive gun laws, (b) widespread gun ownership, (c) and encouragement of armed civilians who can intercept shooters. They cite Switzerland and Israel as exemplars. We evaluate these claims with analysis of International Crime Victimization Survey (ICVS) data and translation of laws and original source material. Swiss and Israeli laws limit firearm ownership and require permit renewal one to four times annually. ICVS analysis finds the United States has more firearms per capita and per household than either country. Switzerland and Israel curtail off-duty soldiers' firearm access to prevent firearm deaths. Suicide among soldiers decreased by 40 per cent after the Israeli army's 2006 reforms. Compared with the United States, Switzerland and Israel have lower gun ownership and stricter gun laws, and their policies discourage personal gun ownership. PMID- 22089894 TI - Application of Gafchromic film in the study of dosimetry methods in CT phantoms. AB - Gafchromic film has been used for measurement of computed tomography (CT) dose distributions within phantoms. The film was calibrated in the beam from a superficial therapy unit and the accuracy confirmed by comparison with measurements with a 20 mm long ionisation chamber. The results have been used to investigate approaches to CT dosimetry. Dose profiles were recorded within standard CT head and body phantoms and scatter tail data fitted to exponential functions and extrapolated to predict dose levels in longer phantoms. The data have been used to simulate both CT dose index (CTDI) measurements with ionisation chambers of differing length and measurements of cumulative doses with a 20 mm chamber for scans of varying length. The results show that the length of a pencil ionisation chamber is the most significant factor affecting measurements of weighted CTDI (CTDI(w)) and a 100 mm chamber would record 50-61% of the dose measured with a 450 mm one. The cumulative dose measured at the centre of a 150 mm long body phantom records over 70% of the equilibrium dose from a helical scan of a longer phantom. For routine CT dosimetry tests, the determination of correction factors could allow measurements with a 100 mm chamber to be used to derive the CTDI that would be recorded with a longer chamber, and cumulative doses measured with a 20 mm chamber in shorter phantoms to be used to calculate equilibrium doses for helical scans. PMID- 22089895 TI - An intervention study in obese mice with astaxanthin, a marine carotenoid- effects on insulin signaling and pro-inflammatory cytokines. AB - Astaxanthin (ASX), a xanthophyll carotenoid from the marine algae Hematococcus pluvialis, has anti-obesity and insulin-sensitivity effects. The specific molecular mechanisms of its actions are not yet established. The present study was designed to investigate the mechanisms underlying the insulin sensitivity effects of ASX in a non-genetic insulin resistant animal model. A group of male Swiss albino mice was divided into two and fed either a starch-based control diet or a high fat-high fructose diet (HFFD). Fifteen days later, mice in each dietary group were divided into two and were treated with either ASX (6 mg kg(-1) per day) in olive oil or olive oil alone. At the end of 60 days, glucose, insulin and pro-inflammatory cytokines in plasma, lipids and oxidative stress markers in skeletal muscle and adipose tissue were assessed. Further, post-receptor insulin signaling events in skeletal muscle were analyzed. Increased body weight, hyperglycemia, hyperinsulinemia and increased plasma levels of tumor necrosis factor-alpha and interleukin-6 observed in HFFD-fed mice were significantly improved by ASX addition. ASX treatment also reduced lipid levels and oxidative stress in skeletal muscle and adipose tissue. ASX improved insulin signaling by enhancing the autophosphorylation of insulin receptor-beta (IR-beta), IRS-1 associated PI3-kinase step, phospho-Akt/Akt ratio and GLUT-4 translocation in skeletal muscle. This study demonstrates for the first time that chronic ASX administration improves insulin sensitivity by activating the post-receptor insulin signaling and by reducing oxidative stress, lipid accumulation and proinflammatory cytokines in obese mice. PMID- 22089896 TI - 3D quantification of mandibular asymmetry using the SPHARM-PDM tool box. AB - PURPOSE: Pretreatment diagnosis of mandibular asymmetry in orthognathic surgery patients can be improved by quantitative shape modeling and analysis. The UNC SPHARM-PDM (University of North Carolina Spherical Harmonics-Point Distribution Model) toolbox was applied to a cohort of patients and the results were evaluated. METHODS: Three-dimensional (3D) virtual surface models are constructed from CBCT scans of each patient in the cohort by segmentation. Mirroring on a sagittal arbitrary plane is used to flip the left and right sides of each image. An automatic voxel-based registration on the cranial base is used to align the volume and its mirror for comparison. SPHARM-PDM is used to compute correspondent models for each hemimandible and the mirror of the contralateral side. Procrustes analysis was used to evaluate discrepancies between each pair of models to assess asymmetry. Mandibular asymmetry was also located and quantified by computing corresponding surface distances between each hemimandible (left and right sides) and the mirror of the contralateral side. RESULTS: There were no statistically significant differences in surrogates for mandibular asymmetry assessment based on right or the left side mirroring. Those surrogates are the rotational and translational differences between each hemimandible and the mirror of the contralateral side in 3 planes of space (the absolute values of Procrustes registration output in 6 degrees of freedom). Absolute and signed distance maps between each hemimandible and the mirror of the contralateral side located and quantified areas of asymmetry diagnosis for each patient. Even though mandibular condyle asymmetry was observed in 8% of the cases and mandibular asymmetry along areas of the ramus and mandibular corpus was noted in 17.8% of the cases, the remaining 74.2% showed generalized morphological and positional asymmetry at the condyle, the ramus and mandibular corpus. CONCLUSION: Three-dimensional diagnosis of mandibular asymmetry revealed the complex involvement of morphological components of the mandible and the heterogeneous nature of this clinical condition. SPHARM-PDM has a promising role in the individual diagnosis and quantification of mandibular asymmetry. PMID- 22089897 TI - Raising concerns about palliative sedation. PMID- 22089901 TI - The unspoken: the stresses of a novice nurse. PMID- 22089903 TI - Nurses on the move! PMID- 22089904 TI - Huddling for optimal care outcomes. PMID- 22089906 TI - Getting "hip" to hip hemiarthroplasty. PMID- 22089907 TI - Too good for this world. PMID- 22089909 TI - Nursing2011 survey results: Blood exposure risk during peripheral I.V. catheter insertion and removal. PMID- 22089910 TI - Beyond mainstream: making the case for fecal bacteriotherapy. PMID- 22089911 TI - Patient education series. Heart attack. PMID- 22089912 TI - 13 tips for surviving the 12-hour shift. PMID- 22089913 TI - New criteria for assessing and treating neuropathic pain. PMID- 22089914 TI - Vitamin D supplementation in chronic kidney disease. PMID- 22089915 TI - Renal colic. PMID- 22089916 TI - Outcome in patients with an infected nonunion of the long bones treated with a reinforced antibiotic bone cement rod. AB - OBJECTIVES: This study looks at the treatment of 16 cases of infection in long bone fractures that had an adverse effect on healing. The goal was to find a method that may be effective in getting these most difficult injuries to heal. The use of reinforced antibiotic-impregnated bone cement rods was studied to see if this could be an effective form of treatment. The use of such devices makes sense because they provide stability that the fractures need for healing while also providing a high concentration of antibiotics locally. The concept was to reduce the amount of metal used for stability while still giving the fracture the correct milieu for healing. DESIGN: This was a retrospective analysis of 16 patients with infected nonunions of long bones. A protocol for the use of intravenous and per oral antibiotics was developed based on the type of bacteria found from cultures of the infected sites. All cases included operative debridement and stabilization with a reinforced antibiotic-impregnated bone cement rod. PATIENTS: The patient population was selected from all those who presented to the Department of Orthopaedic Surgery of Dayanand Medical College & Hospital, Ludhiana, India. MAIN OUTCOME: Success was considered when the nonunion healed and the limb became functional. RESULTS: The infected nonunions were treated successfully in 14 of 16 cases. This represents an alternative to external fixation alone as a means of stabilizing nonunions while providing a high concentration of antibiotic locally for combating this most difficult problem. CONCLUSIONS: The use of reinforced antibiotic-impregnated bone cement rods with appropriate surgical debridement and antibiotics may be an effective way of treating infected nonunions of long bones. LEVEL OF EVIDENCE: Therapeutic Level IV. See page 128 for a complete description of levels of evidence. PMID- 22089917 TI - Less invasive stabilization system (LISS) versus proximal femoral nail anti rotation (PFNA) in treating proximal femoral fractures: a prospective randomized study. AB - OBJECTIVE: To evaluate the outcome and efficacy of LISS (Less Invasive Stabilization System; Synthes USA, Paoli, PA) for the treatment of proximal femoral fractures to find another appropriate minimally invasive surgery for these fractures in which intramedullary nailing may be difficult. DESIGN: A consecutive prospective randomized clinical study. SETTING: University teaching hospital. PATIENTS: Between May 2006 and March 2008, 64 consecutive patients who had a proximal femoral fracture were randomized to be treated with fixation with either LISS or PFNA (Proximal Femoral Nail Anti-rotation; Synthes USA). INTERVENTION: LISS or PFNA fixation of proximal femoral fractures. MAIN OUTCOME MEASUREMENTS: Intraoperative time, intraoperative blood loss, length of hospitalization, hip function (Harris score), general complications, fracture complications. RESULTS: Fifty-nine patients were evaluated with a mean follow-up time of 26.8 months (range, 21-36 months). No statistical differences in general complications, intraoperative blood loss, length of hospitalization, or hip function could be found between the two groups. The average operative time was longer in the LISS group (98.25 minutes) compared with the PFNA group (65.36 minutes) (P < 0.05). One PFNA case had intrapelvic penetration of the helical blade; two LISS cases had breakage of the screws. CONCLUSION: There were no major differences in outcome or complications between the treatment groups. LISS can be used effectively in treating proximal femoral fractures, especially for complex fractures patterns in which intramedullary nailing may be difficult. LEVEL OF EVIDENCE: Therapeutic Level II. See page 128 for a complete description of levels of evidence. PMID- 22089919 TI - Long-term outcome in patients with primary hyperparathyroidism who underwent minimally invasive parathyroidectomy. AB - BACKGROUND: Minimally invasive parathyroidectomy (MIP) has become a well-accepted treatment for selected patients with primary hyperparathyroidism (PHPT). However, few studies have evaluated long-term outcomes for this operative approach. We therefore chose to examine both the long-term symptom resolution and biochemical cure following MIP for PHPT. METHODS: A total of 460 PHPT patients who underwent a MIP between 2004 and 2009 were successfully mailed a questionnaire that assessed preoperative and postoperative Parathyroidectomy Assessment of Symptoms (PAS) scores, most recent calcium and parathyroid hormone (PTH) levels, and information about any reoperation for PHPT. Long-term evaluation of symptomatic and biochemical cure was performed. RESULTS: A total of 200 patients (43.5%) responded to our correspondence. The mean age of the patients was 58.7 +/- 11.9 years, 74.5% were female, and 78.5% were Caucasian. The mean follow-up was 37 +/- 19 months. The mean PAS scores fell by 117 +/- 14 at long-term follow-up after MIP (P < 0.0001). All 13 symptoms comprising the PAS score diminished, of which ten did so significantly (P < 0.01). There was a significant drop in the mean serum calcium (preop. 11.1 mg/dl, postop. 9.6 mg/dl; P < 0.0001) and PTH (preop. 130.9 pg/ml, postop. 45.7 pg/ml; P < 0.0001) at long-term follow-up. Five patients (2.5%) developed recurrent disease (calcium > 10.5 mg/dl), and one (0.5%) underwent a reoperation for persistent disease and was subsequently cured. CONCLUSIONS: This study demonstrates that MIP has long-term benefits in terms of excellent symptom resolution and a high biochemical cure rate (97%) in selected patients who have PHPT, preoperative localization with sestamibi scans, and assessment of intraoperative PTH level. PMID- 22089920 TI - Prognostic relevance of survivin in pancreatic endocrine tumors. AB - BACKGROUND: Better prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors-controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage-was investigated. METHODS: A total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed. RESULTS: Patients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168-281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61-140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24 71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90). CONCLUSIONS: High expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor. PMID- 22089921 TI - Preoperative brain natriuretic peptide (BNP) is a better predictor of adverse cardiac events compared to preoperative scoring system in patients who underwent abdominal surgery. AB - BACKGROUND: Cardiovascular disease is the leading cause of perioperative death in surgical patients. A variety of clinical scoring systems have been developed to predict adverse cardiovascular events. B-type natriuretic peptide (BNP) is a sensitive and specific predictor of left ventricular systolic dysfunction and predicts first cardiovascular event and death in the general population. We present a prospective, single-center, observational cohort study of patients undergoing major abdominal surgery and evaluate the role of BNP in predicting adverse cardiac events. METHOD: A total of 205 patients were included in the study. All patients were assessed by a cardiological clinical evaluation, a 12 lead ECG report, and a preoperative and postoperative blood sample for plasmatic BNP assessment. The primary end point was the predictive power of preoperative BNP levels for adverse cardiac events until 30 days after discharge. RESULTS: Thirty-one of 205 (15%) patients had adverse cardiac events in the postoperative period up to 30 days after discharge. Five patients (2.4%) of these died of cardiac events. Preoperative BNP values were significantly increased in the 31 patients compared to the other patients in the postoperative period [mean = 112.93 pg/ml (range = 5-2,080) vs. 178.99 pg/ml (range = 5-3,980); median = 117 vs. 23 pg/ml; 95% CI = 49-181; p < 0.0001]. At logistic regression, a preoperative BNP value of >36 pg/ml was the only effective predictor of adverse cardiac events. CONCLUSION: We have demonstrated that elevated preoperative BNP levels are independent predictors of adverse cardiac events in a cohort of patients undergoing major abdominal surgery in a general surgery department, and this is the first study about this specific cohort of patients. PMID- 22089922 TI - A unique method for repairing intraoperative pulmonary air leakage with both polyglycolic acid sheets and fibrin glue. AB - BACKGROUND: In the present study we present a unique maneuver, using both fibrin glue and polyglycolic acid (PGA) sheets, for repairing intraoperative pulmonary air leakage, and report our clinical results. METHODS: Based on the results from in vitro experiments, we retrospectively investigated the clinical effects of our method for repairing intraoperative pulmonary air leakage in 377 consecutive patients, who underwent a pulmonary resection for primary lung cancer or metastatic lung tumors from 2004 to 2009. From April 2004 through September 2007, repair of intraoperative pulmonary air leakage was performed in 204 patients using only fibrin glue. From October 2007 through December 2009, the repair was performed in 173 patients with a unique application of both fibrin glue and PGA sheets, i.e., (1) rubbing fibrin glue A solution, (2) applying a PGA sheet cut to an appropriate size, (3) rubbing fibrin glue B solution on the PGA sheet, and (4) reapplying fibrin glue A solution and rubbing. RESULTS: The mean duration of postoperative pleural drainage was significantly shorter in the latter time period when both fibrin glue and PGA sheets were used than in the former period when fibrin glue was used alone. The incidence of prolonged air leakage longer than 1 week was also significantly lower in the latter era than in the former era. CONCLUSION: Our unique application of both fibrin glue and PGA sheets for the intraoperative repair of pulmonary air leakage effectively resulted in a shortening of the duration of postoperative pleural drainage. PMID- 22089923 TI - Bile acid-CoA ligase deficiency--a new inborn error of bile acid metabolism. AB - Born at 27 weeks gestation, a child of consanguineous parents of Pakistani origin required prolonged parenteral nutrition. She developed jaundice, with extensive fibrosis and architectural distortion at liver biopsy; jaundice resolved with supportive care. Serum gamma-glutamyl transpeptidase values were within normal ranges. The bile acids in her plasma and urine were >85% unconjugated (non amidated). Two genes encoding bile-acid amidation enzymes were sequenced. No mutations were found in BAAT, encoding bile acid-CoA : aminoacid N-acyl transferase. The patient was homozygous for the missense mutation c.1012C > T in SLC27A5, predicted to alter a highly conserved amino-acid residue (p.H338Y) in bile acid-CoA ligase (BACL). She also was homozygous for the missense mutation c.1772A > G in ABCB11, predicted to alter a highly conserved amino-acid residue (p.N591S) in bile salt export pump (BSEP). BACL is essential for reconjugation of bile acids deconjugated by gut bacteria, and BSEP is essential for hepatocyte canaliculus export of conjugated bile acids. A female sibling born at term had the same bile-acid phenotype and SLC27A5 genotype, without clinical liver disease. She was heterozygous for the c.1772A > G ABCB11 mutation. This is the first report of a mutation in SLC27A5. The amidation defect may have contributed to cholestatic liver disease in the setting of prematurity, parenteral nutrition, and homozygosity for an ABCB11 mutation. PMID- 22089924 TI - Structure and function of proteins in hydrated choline dihydrogen phosphate ionic liquid. AB - Ionic liquids are being intensely studied as promising media for the stabilization of proteins and other biomolecules. Choline dihydrogen phosphate (CDHP) has been identified as one of the most promising candidates for this application. In this work we have probed in more detail the effects that CDHP may have on the thermodynamics, structure, and stability of proteins, including one of therapeutic interest. Microcalorimetry and circular dichroism spectropolarimetry (CD) were used to assess the thermal stability of protein solutions in CDHP/water mixtures at various concentrations. Increasing thermal stability of lysozyme and interleukin-2 in proportion to CDHP concentration was observed. Isothermal titration calorimetry (ITC) was used to quantify binding interactions, and indicate that the mechanism for stability does not appear to be dependent upon CDHP binding to protein. CD and small angle X-ray scattering (SAXS) analyses were used to probe for structural changes due to the presence of CDHP. SAXS indicates charge effects on the surface of the protein play a role in protein stability in ionic liquids, and no significant alteration of the overall tertiary conformation of lysozyme was observed at 25 degrees C. However, after incubation at 37 degrees C or at higher concentrations of CDHP, small changes in protein structure were seen. Effects on protein activity were monitored using turbidity assays, and CDHP decreases protein activity but does not eliminate it. Protein solubility was also monitored using a turbidity assay and was found to be inversely proportional to the concentration of CDHP in solution. PMID- 22089925 TI - Regulation of rat MOR-1 gene expression after chronic intracerebroventricular administration of morphine. AB - The u-opioid receptor is the primary site for the action of morphine. In the present study, we investigated the regulation of the u-opioid receptor mRNA levels in the locus ceruleus, ventral tegmental area, nucleus accumbens and hypothalamus of the rat brain following intracerebroventricular administration of morphine for 7 days. The isolated mRNA from these regions was subjected to real time quantitative RT-PCR to determine the regulation of u-opioid receptor gene expression. It was observed that 7 days of treatment with morphine significantly down-regulated the u-opioid receptor mRNA levels in the hypothalamus of the brain in comparison to the control group. However, the u-opioid receptor levels in the locus ceruleus, ventral tegmental area and nucleus accumbens regions remained the same as the control levels. Down-regulation of u-opioid receptor mRNA levels in the hypothalamus region of the brain indicates the probable role of opioids to influence neuroendocrine function. The results further indicate that cellular adaptation for morphine tolerance is tissue-specific. These findings help us to understand the mechanism of morphine tolerance in various regions of the brain. PMID- 22089926 TI - In brief: nesiritide (Natrecor). PMID- 22089928 TI - Integration of apoptosis and metabolism. AB - Apoptotic resistance is a hallmark of human cancers. Recent advances have contributed to our understanding of the molecular mechanisms that intimately integrate cell metabolism and apoptosis. Coordinated activation of the proapoptotic Bcl-2 family and the caspase family during apoptosis often leads to permeabilization of the mitochondrial outer membrane and release of multiple enzymes that normally function in regulating energy production and metabolism. The roles of these metabolic enzymes in promoting caspase activation demonstrate a primordial need to couple apoptotic cell death and metabolic catastrophe during cellular destruction. The Bcl-2 family also directly interacts with the multiple metabolic regulators to protect or promote mitochondrial damage during apoptosis. However, the integration of metabolism and apoptosis is not simply limited to the maintenance of mitochondrial integrity. A recent study demonstrates that the NatA complex, a protein N-alpha-acetyltransferase complex, is required for DNA damage mediated apoptosis and suggests that regulation of protein acetylation might provide an important mechanism for regulating apoptotic sensitivity. Since acetyl CoA (coenzyme A) is a key cofactor for the NatA complex, protein acetylation is subject to the availability of acetyl-CoA and, thus, under metabolic regulation. The revelation that protein N-alpha-acetylation is regulated by Bcl-xL, a major antiapoptotic mitochondrial protein, demonstrates a mechanism by which metabolism can regulate the activation of multiple key apoptotic factors simultaneously. PMID- 22089929 TI - Electrophoretic motion of a charged porous sphere within micro- and nanochannels. AB - Electrophoretic motion of a charged porous sphere within micro- and nanochannels is investigated theoretically. The Brinkman model and the full non-linear Poisson Boltzmann equation are adopted to model the system, with the charged porous sphere resembling polyelectrolytes like proteins and DNA. General electrokinetic equations are employed and solved with a pseudo-spectral method. Key parameters of electrokinetic interest are examined for their respective effect as well as overall impact on the particle motion. We found, among other things, that the confinement effect of the channel can be so drastic that 75% reduction of particle mobility is observed in some situations for a poorly permeable particle. However, only 15% for the corresponding highly permeable particle due to the allowance of fluid penetration which alleviates the retarding shear stress significantly. In particular, an intriguing phenomenon is observed for the highly permeable particle: the narrower the channel is, the faster the particle moves! This was experimentally observed as well in the literature on DNA electrophoresis within nanostructures. The reason behind it is thoroughly explained here. Moreover, charged channels can exert electroosmosis flow so dominant that sometimes it may even reverse the direction of the particle motion. Comparison with experimental data available in the literature for some polyelectrolytes is excellent, indicating the reliability of this analysis. The results of this study provide fundamental knowledge necessary to interpret experimental data correctly in various microfluidic and nanofluidic operations involving bio-macromolecules, such as in biosensors and Lab-on-a-chip devices. PMID- 22089927 TI - Cancer and altered metabolism: potential importance of hypoxia-inducible factor and 2-oxoglutarate-dependent dioxygenases. AB - Hypoxia-inducible factor (HIF) deregulation contributes to the Warburg effect. HIF consists of an unstable alpha subunit and a stable beta subunit. In the presence of oxygen, HIFalpha becomes prolyl hydroxylated by members of the EglN (also called PHD) family, leading to its proteasomal degradation. Under hypoxic conditions, EglN activity is diminished and HIF levels rise. EglN1 is the primary HIF prolyl hydroxylase with EglN2 and EglN3 playing compensatory roles under certain conditions. EglN2 and EglN3 also appear to play HIF-independent roles in regulating cell proliferation and apoptosis, respectively. The EglNs belong to a large family of 2-oxoglutarate-dependent dioxygenases that includes the TET DNA hydroxymethylases and JmjC-containing histone demethylases. Members of this superfamily can be inhibited by endogenous metabolites, including fumarate and succinate, which accumulate in tumors that have fumarate hydratase (FH) or succinate dehydrogenase (SDH) mutations, respectively, as well as by the 2 hydroxyglutarate detected in isocitrate dehydrogenase (IDH) mutant tumors. 2 Oxoglutarate-dependent dioxygenases therefore provide a link between altered metabolism and cancer. PMID- 22089930 TI - Enhanced ABL-inhibitor-induced MAPK-activation in T315I-BCR-ABL-expressing cells: a potential mechanism of altered leukemogenicity. AB - BACKGROUND: Targeted treatment of chronic myelogenous leukemia using imatinib has dramatically improved patient outcome. However, residual disease can be detected in the majority of patients treated with imatinib. Compensatory activation of MAP kinases (MAPK1/2) in response to BCR-ABL-inhibitors has been reported as a potential cytokine-dependent resistance mechanism leading to the rescue of leukemic progenitor cells. METHODS: Differential MAPK-modulating activity of clinically approved tyrosine kinase inhibitors was assessed in vitro using BCR ABL-transformed cells. CD34+-enriched progenitors of newly diagnosed chronic myelogenous leukemia patients were exposed to tyrosine kinase inhibitors. MAPK signaling was studied by Western blot technique. Proliferation assays were used to analyze response to antileukemic treatment. RESULTS: The ABL-inhibitors imatinib and nilotinib activate MAPKs in CD34+ chronic myelogenous leukemia progenitor cells, whereas treatment with the SRC/ABL-inhibitor dasatinib does not affect MAPK-activation at clinically relevant concentrations. Similar results are seen in BCR-ABL-transformed cells in the presence of interleukin-3 (IL-3). Experiments using BCR-ABL-mutant T315I, a resistance mutation not amenable to tyrosine kinase inhibitor binding, demonstrate that ABL-inhibitor-induced MAPK activation does not depend on BCR-ABL-inhibition and cannot be prevented by selective SRC-inhibition. However, BCR-ABL-T315I enhances MAPK-activation, suggesting a T315I-dependent positive feedback of MAPK-activation. An autocrine IL-3-loop as trigger for aberrant T315I-dependent MAPK-activation was excluded. CONCLUSIONS: Aberrant MAPK-activation triggered by ABL-inhibitors and positively regulated by BCR-ABL kinase mutation T315I might be an experimental explanation for the clinical observation that patients carrying high-resistance mutations show a highly aggressive course of their disease when tyrosine kinase inhibitor treatment is not discontinued in time. PMID- 22089931 TI - PAX3/7-FOXO1 fusion status in older rhabdomyosarcoma patient population by fluorescent in situ hybridization. AB - PURPOSE: In pediatric alveolar rhabdomyosarcoma, the PAX3-FOXO1 and PAX7-FOXO1 gene fusions are prognostic indicators, while little is known concerning this disease in older patients. To determine whether PAX3/7-FOXO1 fusion gene status correlates with outcome in adolescent, young adult, and adult rhabdomyosarcoma patients, the histological, immunohistochemical, and clinical characteristics of 105 patients followed at The University of Texas MD Anderson Cancer Center from 1957 to 2001 were evaluated. METHODS: The samples were assembled into a tissue microarray, and fusion gene status was determined by fluorescence in situ hybridization using PAX3, PAX7, and FOXO1 loci-specific probes. The disease characteristics and specific gene fusion were correlated with patient outcomes using the log-rank test. RESULTS: Fifty-two percent of the samples exhibited a PAX3-FOXO1 fusion, 15% the PAX7-FOXO1 fusion, and 33% were negative for a rearrangement of these loci. The presence of PAX3/7-FOXO1 translocation was significantly associated with a higher frequency of metastatic disease. Although a statistically significant correlation between the PAX3/7-FOXO1 fusion gene status and overall survival was not identified, there was a trend toward better outcomes for patients with fusion-negative RMS. CONCLUSIONS: Therefore, identification of a FOXO1 fusion appears to be an interesting tool for predicting outcomes in older rhabdomyosarcoma patients and is worth further investigations in this rare subgroup of RMS population. PMID- 22089933 TI - Interactions of amyloid beta peptide 1-40 and cerebrosterol. AB - Amyloid beta peptides appear to play a role in physiological processes; however, they are also involved in the pathogenesis of Alzheimer disease. Their actions under normal conditions are probably mediated by soluble monomeric L-isoforms at low concentrations, perhaps via highly specific interactions. On the contrary, toxic effects of aggregated natural L-isoforms/synthetic D-isoforms on membranes are very similar, but synthetic reverse/random L: -isoforms without pronounced aggregation properties are not toxic. Our previous work reported interactions of non-aggregated/aggregated L-isoforms of amyloid beta peptides 1-40/1-42 with racemic 24-hydroxycholesterol. In this study, stereospecificity in the interactions of natural 24(S)hydroxycholesterol (cerebrosterol) or synthetic 24(R)hydroxycholesterol with soluble fragment 1-40 was evaluated by means of an in vitro test based on increased vulnerability of the hemicholinium-3 sensitive high-affinity choline uptake system in rat hippocampal cholesterol-depleted synaptosomes to the actions of amyloid beta; computational simulations were also performed. Our results suggest that: (1) 24(S)hydroxycholesterol interacts with L peptide 1-40 but not with the reverse L-peptide 40-1, (2) 24(R)hydroxycholesterol does not interact with L-peptide 1-40 or reverse 40-1, and (3) both enantiomers can probably interact with D-peptide 1-40. Therefore, the binding of 24(S)hydroxycholesterol is not fully stereospecific and the interaction could not reflect a physiological mechanism. Data from the computational simulation indicate that the hydrophobic core of the amyloid beta molecule interacts with the hydrophobic part of 24(S)hydroxycholesterol, but no hydrogen bonds with high stability were found. Using this procedure, globular amyloid beta could retain 24(S)hydroxycholesterol and thus contribute to its pathological accumulation in the brains of patients with Alzheimer disease. PMID- 22089932 TI - Neuroprotective effect of sesame seed oil in 6-hydroxydopamine induced neurotoxicity in mice model: cellular, biochemical and neurochemical evidence. AB - Natural antioxidants have shown a remarkable reduction in oxidative stress due to excess formation of reactive oxygen species by enhancing antioxidant mechanism in the neurodegenerative disorders. Sesame seed oil (SO) is one of the most important edible oil in India as well as in Asian countries and has potent antioxidant properties thus the present study evaluated the neuroprotective effect of SO by using 6-Hydroxydopamine (6-OHDA)-induced Parkinson's disease model in mice. The mice were fed an SO mix diet for 15 days and then 6-OHDA was injected into the right striatum of mice brain. Three weeks after 6-OHDA infusion, mice were sacrificed and the striatum was removed. The neuroprotective role of SO on the activities of antioxidant and non-antioxidant enzymes such as glutathione reductase (GR), glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and content of glutathione (GSH) and thiobarbituric acid reactive substance (TBARS) were studied in the striatum. The activities of all the above-mentioned enzymes decreased significantly in 6-OHDA group (Lesioned) when compared with Sham. The pretreatment of SO on antioxidant mechanism and dopamine level in the brain had shown some significant improvement in Lesion+SO (L+SO) group when compared with Lesioned group. However, NADPH oxidase subunit, Nox2 and inflammatory stimulator Cox2 expression was increased as well as antioxidant MnSOD level was decreased in Lesioned group while SO showed the inhibitory effect on the activation of Nox2 and Cox2 and restored MnSOD expression in L+SO group. Increased tyrosine hydroxylase (TH) expression in substantia nigra as well as dopamine and its metabolite DOPAC level in L+SO group also support our findings that SO may inhibit activation of NADPH oxidase dependent inflammatory mechanism due to 6-OHDA induced neurotoxicity in mice. PMID- 22089935 TI - Organocatalytic asymmetric tandem condensation-intramolecular rearrangement protonation: an approach to optically active alpha-amino thioester derivatives. AB - An unprecedented and conceptually novel chiral Bronsted base/Bronsted acid catalytic method for the enantioselective synthesis of alpha-amino thioesters through a tandem condensation-intramolecular rearrangement-protonation has been developed which provides a number of important synthetic building blocks in good yield and with moderate to good enantioselectivities. PMID- 22089934 TI - Striatal GABA receptor alterations in hypoxic neonatal rats: role of glucose, oxygen and epinephrine treatment. AB - Hypoxia in neonates disrupts the oxygen flow to the brain, essentially starving the brain and preventing it from performing vital biochemical processes important for central nervous system development. Hypoxia results in a permanent brain damage by gene and receptor level alterations mediated through neurotransmitters. The present study evaluated GABA, GABAA, GABAB receptor functions and gene expression changes in glutamate decarboxylase in the corpus striatum of hypoxic neonatal rats and the treatment groups with glucose, oxygen and epinephrine. Since GABA is the principal neurotransmitter involved in hypoxic ventilatory decline, the alterations in its level under hypoxic stress points to an important aspect of respiratory control. Following hypoxic stress, a significant decrease in total GABA, GABAA and GABAB receptors function and GAD expression was observed in the striatum, which accounts for the ventilator decline. Hypoxic rats treated with glucose alone and with oxygen showed a reversal of the receptor alterations and changes in GAD to near control. Being a source of immediate energy, glucose can reduce the ATP-depletion-induced changes in GABA and oxygenation helps in overcoming reduction in oxygen supply. Treatment with oxygen alone and epinephrine was not effective in reversing the altered receptor functions. Thus, our study point to the functional role of GABA receptors in mediating ventilatory response to hypoxia and the neuroprotective role of glucose treatment. This has immense significance in the proper management of neonatal hypoxia for a better intellect in the later stages of life. PMID- 22089936 TI - Mothers' perspectives on their child's mental illness as compared to other complex disorders in their family: insights to inform genetic counseling practice. AB - To facilitate the development of a therapeutic alliance in genetic counseling, it is important that the counselor understands how families might perceive the condition that constitutes the reason for the referral. Through training and professional practice, genetic counselors develop a thorough understanding of families' perceptions of the conditions that are common indications for genetic counseling. But, for referral indications that are less frequent, like serious mental illnesses, genetic counselors may feel less confident in their understanding of the family's experience, or in their ability to provide psychosocial support when serious mental illness is reported in a family history. This may impede the establishment of a therapeutic alliance. As research shows that most referrals for genetic counseling related to serious mental illness are for female first-degree family members of affected individuals, we sought to explore how this group perceives serious mental illness. To provide a frame of reference with which genetic counselors may be more familiar, we explored how women perceived serious mental illness compared to other common complex disorders in their family. We conducted semi-structured interviews with women who had a child with a serious mental illness (schizophrenia, schizoaffective disorder, bipolar disorder) and a first-degree relative with another common complex disorder (diabetes, heart disease, cancer). Interviews were transcribed and subjected to thematic analysis. Saturation was reached when nine women had participated. Serious mental illness was perceived as being more severe and as having a greater impact on the family than diabetes, heart disease, or cancer. Themes identified included guilt, stigma, and loss. Some of the most important issues that contribute to mothers' perceptions that serious mental illness is more severe than other common complex disorders could be effectively addressed in genetic counseling. Developing a heightened awareness of how family members experience a relative's mental illness may help genetic counselors to be better able to provide psychosocial support to this group, whether serious mental illness constitutes the primary reason for referral or appears in the family history during counseling for a different referral reason. PMID- 22089938 TI - Clinical course of postthrombotic syndrome in children with history of venous thromboembolism. AB - Postthrombotic syndrome (PTS) is a chronic morbidity of venous thromboembolism (VTE) in children. Information about the evolution of PTS is lacking in children. Present study was aimed to evaluate the time-course of extremity PTS in children who were serially followed in a hematology clinic. This retrospective cohort study included 69 consecutive children with documented VTEs that presented with symptoms of extremity VTE: 67 extremity VTEs with or without extension to vena cava, 2 inferior vena cava VTEs. Severity of PTS was assessed using modified Villalta scale. Median age of the cohort was 12.6 years (interquartile range 1.6 15 years) while median follow-up was 28.7 months (interquartile range 13.3-33.4 months. PTS prevalence was 46.8% [95% confidence interval (CI) 37.9-57.7%]. Lower extremity VTE was associated with development of PTS compared to upper extremity VTE regardless of catheter use (P = 0.002). The time-course of PTS fluctuated in 11 of 33 children (33%; 95% CI 20-47%) at a median interval of 12 months from diagnosis of VTE (range 4-14 months): three progressed from mild/moderate to severe, one improved from moderate to mild, seven fluctuated between mild and moderate. Recurrence and incomplete resolution of VTE were associated with variability in PTS severity (P < 0.05). In summary, this study suggested that almost 50% of study cohort developed PTS, and the time-course of PTS was not static in one third of children. Future research should focus on identifying the predictors contributing to the worsening of PTS and developing risk-stratified treatment interventions so as to improve the outcome of children with VTE. PMID- 22089939 TI - Structure and function of von Willebrand factor. AB - von Willebrand factor (VWF) is a long plasma protein that contains many domains and each domain has its own function. VWF exists in a multimeric form and performs varieties of functions in the human body, including thrombus formation and blood coagulation. The crystal structures of three subdomains are known, and, interestingly, all three domains share identical three-dimensional fold with alpha-beta-alpha sandwiched model. VWF is directly associated with different types of von Willebrand disease. In this review, our aim is to gather recent developments on structure and functions of VWF and its clinical relevance. PMID- 22089940 TI - Impact of reduced levels of protein C, free protein S and antithrombin in normal frozen plasma on the interpretation of patients' results. AB - The objective of this study was to investigate the effect of freezing of normal plasma samples on protein C, free protein S (FPS) and antithrombin levels in order to determine its potential impact on the interpretation of the results of similarly frozen patients' samples. Protein C, FPS and antithrombin levels were measured by clotting-based test, by sandwich ELISA and by chromogenic assay, respectively, in 50 normal plasma samples prior to freezing, and after 2 and 4 weeks in parallel aliquots frozen at -25 degrees C. The mean levels of the three proteins dropped significantly after a fortnight's freezing, protein C: 130.7 122.8% (P < 0.0246); FPS: 105.9-94.1% (P < 0.0016); antithrombin: 103.2-95.8% (P < 0.0001). The corresponding inter-assay coefficient of variances of the two sets of results were 8.9, 6.6 and 9.3%. Thereafter, only FPS declined significantly (84.3%) (P < 0.0001). In two of 48 and five of 48 cases at the end of 2 and 4 weeks, respectively, the levels of FPS values went below the lower limit of the normal range established from the 50 plasma samples. Freezing of plasma at -25 degrees C for 24 h per se did not alter the levels of protein C and antithrombin and caused only a negligible change in FPS levels. Since 6, 4 and 14% of normal plasma samples would have been labeled as antithrombin, protein C and protein S deficient, respectively, had the tests been performed after 4 weeks of freezing, it is recommended that for correct interpretation of the results, laboratories should establish their reference ranges on normal samples frozen for the same period of time as the patients' samples. PMID- 22089941 TI - Intravenous thrombolysis on early recurrent cardioembolic stroke: 'Dr Jekyll' or 'Mr Hyde'? AB - Early recurrent cardioembolic stroke on the previously unaffected side has very rarely been reported during or after intravenous recombinant tissue plasminogen activator for acute ischemic stroke. For these cases, thrombolysis guidelines lack any clear recommendation. We report two cases of thrombolysed stroke patients, with paroxysmal atrial fibrillation but normal sinus rhythm on admission, who respectively developed recurrent ischemic stroke within few hours after complete improvement and during intravenous recombinant tissue plasminogen activator infusion. Intravenous thrombolysis was successfully repeated after echocardiographic evidence of left appendage thrombus in the first case and discontinued before complete administration in the second. PMID- 22089942 TI - Capsaicin-induced inhibition of platelet aggregation is not mediated by transient receptor potential vanilloid type 1. AB - Capsaicin is an agonist of transient receptor potential vanilloid type 1 (TRPV1), in which it can act as a neuronal stimulant and result in nociception. Capsaicin also affects a variety of nonneuronal tissues, in which its mechanisms of action are less certain. The present study investigated whether the inhibitory effects of capsaicin on platelet aggregation are mediated via TRPV1. Venous whole blood obtained from beagle dogs (n = 6) was preincubated with capsaicin and/or the potent and selective competitive TRPV1 antagonist, A-993610 and then exposed to collagen (2 MUg/ml). An aggregometer was used to quantify the platelet response. Capsaicin exposure inhibited collagen-induced platelet aggregation in a concentration-dependent manner, with significant effects at 10 and 30 MUg capsaicin per millilitre. A-993610 alone (0.1-1.0 MUg/ml) had no effects on collagen-induced platelet aggregation, nor did it have any effects on capsaicin's ability to inhibit platelet aggregation. The current results agree with previous findings that capsaicin can inhibit platelet aggregation. In addition, the present study demonstrates that capsaicin's inhibitory effect on collagen-induced canine platelet aggregation is not mediated by TRPV1. PMID- 22089943 TI - Effects of four commercially available factor Xa proteins on the fluorogenic anti factor Xa assay when monitoring unfractionated heparin. AB - Four commercially available factor Xa (FXa) reagents were evaluated in a fluorogenic anti-FXa assay. The four reagents - of which three were of human origin and the fourth was bovine - were compared in terms of the resulting assay dynamic ranges, lag times, coefficient of variation and R2 values, as well as their sensitivity to unfractionated heparin within the therapeutic range of 0-1.2 U/ml. Similar performance of reagents in the fluorogenic anti-FXa assay was observed independent of the source of the reagent or its physical state, which may assist in the standardization of coagulation assays in clinical settings. PMID- 22089944 TI - A Markov decision model for determining optimal outpatient scheduling. AB - Managing an efficient outpatient clinic can often be complicated by significant no-show rates and escalating appointment lead times. One method that has been proposed for avoiding the wasted capacity due to no-shows is called open or advanced access. The essence of open access is "do today's demand today". We develop a Markov Decision Process (MDP) model that demonstrates that a short booking window does significantly better than open access. We analyze a number of scenarios that explore the trade-off between patient-related measures (lead times) and physician- or system-related measures (revenue, overtime and idle time). Through simulation, we demonstrate that, over a wide variety of potential scenarios and clinics, the MDP policy does as well or better than open access in terms of minimizing costs (or maximizing profits) as well as providing more consistent throughput. PMID- 22089945 TI - Optimizing renal replacement therapy in older adults: a framework for making individualized decisions. AB - It is often difficult to synthesize information about the risks and benefits of recommended management strategies in older patients with end-stage renal disease since they may have more comorbidity and lower life expectancy than patients described in clinical trials or practice guidelines. In this review, we outline a framework for individualizing end-stage renal disease management decisions in older patients. The framework considers three factors: life expectancy, the risks and benefits of competing treatment strategies, and patient preferences. We illustrate the use of this framework by applying it to three key end-stage renal disease decisions in older patients with varying life expectancy: choice of dialysis modality, choice of vascular access for hemodialysis, and referral for kidney transplantation. In several instances, this approach might provide support for treatment decisions that directly contradict available practice guidelines, illustrating circumstances when strict application of guidelines may be inappropriate for certain patients. By combining quantitative estimates of benefits and harms with qualitative assessments of patient preferences, clinicians may be better able to tailor treatment recommendations to individual older patients, thereby improving the overall quality of end-stage renal disease care. PMID- 22089946 TI - Issues regarding 'immortal time' in the analysis of the treatment effects in observational studies. AB - In observational studies, treatment is often time dependent. Mishandling the time from the beginning of follow-up to treatment initiation can result in bias known as immortal time bias. Nephrology researchers who conduct observational research must be aware of how immortal time bias can be introduced into analyses. We review immortal time bias issues in time-to-event analyses in the biomedical literature and give examples from the nephrology literature. We also use simulations to quantify the bias in different methods of mishandling immortal time; intuitively explain how bias is introduced when immortal time is mishandled; raise issues regarding unadjusted treatment comparison, patient characteristics comparison, and confounder adjustment; and, using data from DaVita Inc., linked with the Centers for Medicare & Medicaid Services end-stage renal disease database, show that the severity of bias and the issues described can occur in actual data analyses of patients with end-stage renal disease. In the simulation examples, mishandling immortal time led to an underestimated hazard ratio (treatment vs. control), thus an overestimated treatment effect, by as much as 96%, and an overestimated hazard ratio by as much as 138%, depending on the distribution of 'survival' time and the method used. Results from the DaVita data were consistent with the simulation. Careful consideration of methodology is needed in observational analyses with time-dependent treatment. PMID- 22089947 TI - Forty years and counting... PMID- 22089948 TI - Illustrative assessment of human health issues arising from the potential release of chemotoxic substances from a generic geological disposal facility for radioactive waste. AB - Many countries have a programme for developing an underground geological disposal facility for radioactive waste. A case study is provided herein on the illustrative assessment of human health issues arising from the potential release of chemotoxic and radioactive substances from a generic geological disposal facility (GDF) for radioactive waste. The illustrative assessment uses a source pathway-receptor methodology and considers a number of human exposure pathways. Estimated exposures are compared with authoritative toxicological assessment criteria. The possibility of additive and synergistic effects resulting from exposures to mixtures of chemical contaminants or a combination of radiotoxic and chemotoxic substances is considered. The case study provides an illustration of how to assess human health issues arising from chemotoxic species released from a GDF for radioactive waste and highlights potential difficulties associated with a lack of data being available with which to assess synergistic effects. It also highlights how such difficulties can be addressed. PMID- 22089949 TI - Growth of lung cancer cells in three-dimensional microenvironments reveals key features of tumor malignancy. AB - Cultured human lung cancer cell lines have been used extensively to dissect signaling pathways underlying cancer malignancy, including proliferation and resistance to chemotherapeutic agents. However, the ability of malignant cells to grow and metastasize in vivo is dependent upon specific cell-cell and cell extracellular matrix (ECM) interactions, many of which are absent when cells are cultured on conventional tissue culture plastic. Previous studies have found that breast cancer cell lines show differential growth morphologies in three dimensional (3D) gels of laminin-rich (lr) ECM, and that gene expression patterns associated with organized cell structure in 3D lrECM were associated with breast cancer patient prognosis. We show here that established lung cancer cell lines also can be classified by growth in lrECM into different morphological categories and that transcriptional alterations distinguishing growth on conventional tissue culture plastic from growth in 3D lrECM are reflective of tissue-specific differentiation. We further show that gene expression differences that distinguish lung cell lines that grow as smooth vs. branched structures in 3D lrECM can be used to stratify adenocarcinoma patients into prognostic groups with significantly different outcome, defining phenotypic response to 3D lrECM as a potential surrogate of lung cancer malignancy. PMID- 22089950 TI - Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis 2000-2011. AB - BACKGROUND: The aim of this study is to provide a contemporary quantitative analysis of the existing literature examining the relationship between surgical caseload and outcome following esophageal resection. METHODS: Medline, Embase, trial registries, conference proceedings and reference lists were searched for trials comparing clinical outcome following esophagectomy from high- and low volume hospitals since 2000. Primary outcomes were in-hospital and 30-day mortality. Secondary outcomes were length of hospital stay and post-operative complications. RESULTS: Nine appropriate publications comprising 27,843 esophagectomy operations were included, 12,130 and 15,713 operations were performed in low- and high-volume surgical units, respectively. Esophagectomy at low-volume hospitals was associated with a significant increase in incidence of in-hospital (8.48% vs. 2.82%; pooled odds ratio (POR) = 0.29; P < 0.0001) and 30 day mortality (2.09% vs. 0.73%; POR = 0.31; P < 0.0001). There was insufficient data for conclusive statistical analysis of length of hospital stay or post operative complications. CONCLUSIONS: This meta-analysis does suggest a benefit in the centralization of esophageal cancer surgery to high-volume institutions with respect to mortality. The outcomes of this study are of interest to patients, healthcare providers and payers, particularly regarding service reconfiguration and more specifically centralization of services. Future studies that look at long-term survival will help improve understanding of any late consequences such as survival and quality of life following esophageal surgery at low- and high-volume hospitals. PMID- 22089951 TI - Is there a role for surgery with adequate nodal evaluation alone in gastric adenocarcinoma? AB - INTRODUCTION: The extent of lymphadenectomy and protocol design in gastric cancer trials limits interpretation of survival benefit of adjuvant therapy after surgery with adequate lymphadenectomy. We examined the impact of surgery with adequate nodal evaluation alone on gastric cancer survival. METHODS: Using 2001 2008 California Cancer Registry, we identified 2,229 patients who underwent gastrectomy with adequate nodal evaluation (>=15 lymph nodes) for American Joint Committee on Cancer stage I-IV M0 gastric adenocarcinoma. Cox proportional hazard analyses were used to evaluate the impact of surgery alone on survival. RESULTS: Nearly 70% of our cohort had T1/2 tumors and 29% had N0 disease. Forty-nine percent of the cohort underwent surgery alone. These patients were more likely to be older, Medicare-insured, with T1 and N0 disease. On unadjusted analyses, persons who underwent surgery alone for stage I or N0 disease experienced 1- and 3-year overall and cancer-specific survival comparable to those who received adjuvant therapy. On multivariate analyses for stage I or N0 disease, surgery alone predicted superior survival outcomes than when combined with adjuvant therapies. CONCLUSION: Surgery alone with adequate nodal evaluation may have a role in low-risk gastric cancer. To corroborate these findings, surgery with adequate lymphadenectomy alone (as treatment arm) deserves consideration in the design of gastric cancer trials to provide effective yet resource-conserving, rather than maximally tolerated, treatments. PMID- 22089952 TI - Outcomes of primary surveillance for intraductal papillary mucinous neoplasm. AB - BACKGROUND: Limited data are available regarding the natural history of patients undergoing primary surveillance for intraductal papillary mucinous neoplasm (IPMN). We hypothesize that symptoms, radiologic characteristics, and cytopathology will predict cancer risk during surveillance. METHODS: Between March 2002 and March 2010, 522 patients were diagnosed with IPMN at a single, high-volume institution. Low versus high oncologic risk was stratified prospectively. Patients with under 3 months of surveillance were excluded. RESULTS: Two hundred ninety-two patients underwent primary surveillance for IPMN. Two hundred forty-four (84%) were classified as low-risk IPMN. Mean surveillance duration was 35 (4-99) months. Thirty (12%) patients initially stratified as low risk developed a new indication for pancreatic resection. Only 28 underwent resection, and pathologic tissue analysis revealed 27 (96%) low-grade IPMN and one (4%) high-grade dysplastic IPMN. Overall, two (1%) patients initially determined to be low-risk developed invasive cancer. Forty-eight (16%) patients stratified as high-risk IPMN were initially managed nonoperatively. Of the 13 (27%) high-risk patients that died during follow-up, two (15%) died from pancreatic cancer. CONCLUSIONS: Progression to pancreatic cancer during surveillance for low-risk IPMN was rare. Current indications for resection did not forecast malignancy. Poor operative candidates with high-risk IPMN progressed to invasive cancer more commonly, though a substantial portion succumbed to non IPMN-related death. PMID- 22089953 TI - Reflux esophagitis and marginal ulcer after pancreaticoduodenectomy. PMID- 22089955 TI - Protection against ischemic cochlear damage by intratympanic administration of AM 111. AB - OBJECTIVE: AM-111, a cell-permeable peptide inhibitor of c-Jun N-terminal kinase, was investigated for its protective effects against ischemic damage of the cochlea in gerbils. METHODS: Transient cochlear ischemia was introduced in animals by occluding the bilateral vertebral arteries for l5 minutes. Then, 10 MUl of AM-111 at a concentration of l, 10, or 100 MUM in hyaluronic acid gel formulation was applied onto the round window 30 minutes after the insult. Gel without active substance was used in a control group. Treatment effects were evaluated by auditory brainstem response (ABR) and histology of the inner ear. RESULTS: In controls, transient cochlear ischemia caused a 25.0 +/- 5.0 dB increase in the ABR threshold at 8 kHz and a decrease of 13.3 +/- 2.3% in inner hair cells at the basal turn on Day 7. Ischemic damage was mild at 2 and 4 kHz. When the animals were treated with AM-111 at 100 MUM, cochlear damage was significantly reduced: the increase in ABR threshold was 3.3 +/- 2.4 dB at 8 kHz, and the inner hair cell loss was 3.1 +/- 0.6% at the basal turn on Day 7. The effects of AM-111 were concentration dependent: 100 MUM was more effective than 1 or 10 MUM. CONCLUSION: Direct application of AM-111 in gel formulation on the round window was effective in preventing acute hearing loss because of transient cochlear ischemia. PMID- 22089954 TI - Epidermal growth factor expression in esophageal adenocarcinoma: a clinically relevant target? AB - INTRODUCTION: There has been recent widespread enthusiasm in epidermal growth factor (EGFR) as a molecularly active target in esophageal adenocarcinoma (EAC). However, there is limited data on the extent of EGFR expression in EAC. Thus, the aim of this study was to evaluated EGFR, pErk1/2, and total Erk1/2 expression in malignant and benign specimens. METHODS: Baseline expression of EGFR in the human normal squamous, Barrett's, and EAC cell lines were determined as well as after bile acid treatment and curcumin pretreatment. In addition, EGFR expression was also evaluated in 60 matched normal and malignant EAC resected specimens. RESULTS: The in vitro studies in the Het-1a, BarT, and OE19 cell lines failed to show any measurable expression of EGFR via Western blot technique. The marker serving as the positive control for the study, MnSOD, showed expression in each cell line for all three treatment regimens at approximately 24 kDa EGFR, showing moderate staining in the malignant tumor specimens and low staining in the benign tissue specimens. pErk1/2 showed low staining in the malignant tumor specimens and no staining in the benign tissue specimens. Total Erk1/2 showed high staining in both the malignant tumor specimens and benign tissue specimens. The differences in the mean staining scores for the malignant versus benign tissue specimens for pErk1/2 and total Erk1/2 are not statistically significant (p = 0.0726 and p = 0.7054, respectively). CONCLUSION: Thus, in conclusion, EGFR expression has been confirmed to be limited to non-existent in EAC and thus its use as a clinically active target is limited at best. Prior to the use of these expensive anti-EGFR therapies, confirmation of overexpression should be verified. PMID- 22089956 TI - Intratympanic dexamethasone is an effective method as a salvage treatment in refractory sudden hearing loss. AB - OBJECTIVES: This study aimed to investigate the therapeutic efficacy of intratympanic dexamethasone (ITD) as a salvage treatment in sudden hearing loss (SHL) patients who had no response to initial systemic combination steroid therapy. PATIENTS AND METHODS: From May 2007 to June 2010, 415 SHL patients visited 3 tertiary referral centers within 7 days of disease onset. They were all treated with an identical protocol, a 10-day scheduled hospitalization and oral steroid treatment. Of these, 151 patients were totally unresponsive 2 weeks after treatment initiation according to Siegel's criteria. We divided these 151 refractory patients into 3 groups: those receiving no further treatment (control group, n = 59), those receiving one more 10-day cycle of oral steroids (systemic reapplication group, n = 26), and those receiving ITD therapy (ITD group, n = 66). Final assessment of hearing was conducted approximately 3 months after the onset of SHL. Hearing improvement was defined as demonstrating "any" improvement according to Siegel's criteria. RESULTS: The initial average hearing thresholds of all groups were similar. Overall hearing improvement was observed in 10 of 59 patients in the control group, in 4 of 26 in the systemic reapplication group, and in 32 of 66 in the ITD group. No serious complications were observed. Analyzing by frequency, paradoxically, hearing of the low and mid frequencies was more significantly improved than high frequencies in the ITD group. CONCLUSION: Intratympanic dexamethasone administration after failure of an initial treatment is effective, and this should be used as a salvage treatment in cases of refractory SHL. PMID- 22089957 TI - Hearing preservation via a cochleostomy approach and deep insertion of a standard length cochlear implant electrode. AB - OBJECTIVE: The suggestion that the depth of insertion of the electrode into the cochlea is critical to hearing preservation has led to the development of a generation of short electrodes designed to minimize intracochlear trauma and avoid contact with the apical region of the cochlea. This study aims to describe our experience of hearing preservation surgery using a deeply inserted standard length electrode array covering the region of residual hearing. STUDY DESIGN: A retrospective case note review was performed identifying cases of attempted hearing preservation using standard length electrodes. SETTING: Study based at Manchester Royal Infirmary, a tertiary referral center. PATIENTS: Fourteen cochlear implants in 13 patients were identified for further analysis from the Manchester Cochlear Implant Programme database. INTERVENTION(S): Each patient received the same design of implant using a "soft" surgical technique. MAIN OUTCOME MEASURE: Preoperative and postoperative air conduction thresholds were compared to assess the degree of hearing preservation. RESULTS: Successful hearing preservation was demonstrated in 12 of 14 cases, and the postoperative residual hearing thresholds in 3 adolescents receiving a standard length electrode array were found to have improved. Preservation of speech recognition was not measured in this study, rather hearing was tested by pure tone audiogram. Follow-up at the time of this study ranged from 1 week to 23 months. CONCLUSION: This study demonstrates that deep insertion of the electrode into the cochlea does not preclude successful hearing preservation. It also highlights that residual hearing can be consistently preserved using a "cochleostomy" approach. PMID- 22089958 TI - Efficacy of a vibrotactile neurofeedback training in stance and gait conditions for the treatment of balance deficits: a double-blind, placebo-controlled multicenter study. AB - OBJECTIVE: Vestibular rehabilitation strategies mostly require a long-lasting training in stance conditions, which is finally not always successful. The individualized training in everyday-life conditions with an intuitive tactile neurofeedback stimulus seems to be a more promising approach. Hence, the present study was aimed at investigating the efficacy of a new vibrotactile neurofeedback system for vestibular rehabilitation. STUDY DESIGN: Double-blinded trial. PATIENTS: One hundred five patients who experience one of the following balance disorders for more than 12 months were included in the study: canal paresis, otolith disorder, removal of an acoustic neuroma, microvascular compression syndrome, Parkinson's disease, and presbyvertigo. INTERVENTIONS: Vibrotactile neurofeedback training was performed daily (15 min) over 2 weeks with the Vertiguard system in those 6 tasks of the Standard Balance Deficit Test with the most prominent deviations from the normative values. MAIN OUTCOME MEASURES: Trunk and ankle sway, dizziness handicap inventory, and vestibular symptom score were measured in the verum and placebo group before the training, on the last training day and 3 months later. RESULTS: A significant reduction in trunk and ankle sway as well as in the subjective symptom scores were observed in the verum group. Such an effect could not be found in any of the outcome parameters of the placebo group. CONCLUSION: The vibrotactile neurofeedback training applied in the present study is a highly efficient method for the reduction of body sway in different balance disorders. Because the rehabilitation program is easy to perform, not exhausting, and time saving, elderly patients and those with serious, long lasting balance problems also can participate successfully. PMID- 22089959 TI - A pilot study on safety climate in Chinese hospital. AB - OBJECTIVES: The present paper has 2 primary objectives as a pilot study on health care safety climate in China: to develop its prototypical model well fit to the country's current hospital situations and validated external reliability and to elicit essential characteristics of safety climate for hypothetical general features in Chinese health care. METHODS: A safety climate survey was carried out in 2008 at a university hospital in Shanghai, using an Operating Room Management Attitudes Questionnaire. We collected 1056 valid responses from doctors and nurses with 81% of overall response rate. RESULTS: A 9-dimension model of safety climate was developed by applying principal component analysis to the entire sample with 44% of cumulative variance accounted for. Compared with the Japanese sample, safety climate in the Chinese hospital was characterized as strong awareness of own competence, positive attitudes to organization, but large power distance and unrealistic staff recognition of human error. Criterion validity of the construct was in part assured by significant correlations of 4 dimensions with self-reported staff behavior of accident reporting. CONCLUSIONS: Safety climate has been not yet mature in the hospital surveyed that might be partly tied with blame culture. Considering health-care policies, procedures, and management styles shared with many other health-care organizations as well as Chinese culture, we would hypothesize that the immature nature is common in Chinese health care as overall characteristics of safety climate. From these results, we would suggest that a nonpunitive health-care culture should be fostered to improve patient safety in China. PMID- 22089960 TI - Targeting the host-pathogen interface for treatment of Staphylococcus aureus infection. AB - Recent emergence of methicillin-resistant Staphylococcus aureus both within and outside healthcare settings has accelerated the use of once reserved last line antibiotics such as vancomycin. With increased use of antibiotics, there has been a rapid rise in the rate of resistance development to the anti-MRSA drugs. As the antibiotic pipeline becomes strained, alternative strategies are being sought for future treatment of S. aureus. Here, we review several novel anti-staphylococcal strategies that, unlike conventional antibiotics, do not target essential gene products elaborated by the pathogen. The approaches seek instead to weaken the S. aureus defense by neutralizing its virulence factors or boosting host immunity. Other strategies target commensal bacteria that naturally colonize the human host to inhibit S. aureus colonization. Ultimately, the aim is to shift the balance between host defense and pathogen virulence in favor of inhibition of S. aureus pathogenic activities. PMID- 22089961 TI - A pilot study of a crossover trial with randomized use of ankle-foot orthoses for people with Charcot-Marie-tooth disease. AB - OBJECTIVES: This was a pilot and feasibility study of a crossover trial with randomized use of ankle-foot orthoses by people with Charcot-Marie-tooth (CMT) disease, investigating the effects of these on gait parameters, practical aspects of use and achievement of goals. DESIGN: A randomized crossover trial. SETTING: The community and ambulatory care. PARTICIPANTS: Eight adults with CMT disease type 1 or 2. INTERVENTIONS: LigaflexTM, custom-made polypropylene and silicone ankle-foot orthoses worn in randomized order for three weeks each, with a washout week in-between; the orthoses of each participant's choice were then worn until 28 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was gait velocity; other outcome measures included Goal Attainment Scaling; Likert scores, concerning aspects of orthosis use and gait analysis parameters. RESULTS: Gait velocity was greatest wearing polypropylene orthoses, median 0.96 (interquartile range (IQR) 0.75-1.18) ms(-1), compared with silicone orthoses, median 0.88 (0.71 1.12) ms(-1), and no orthosis, median 0.79 (0.56-0.84) ms(-1), P=0.006. The silicone orthoses met goals more successfully and scored more favourably for comfort, 5.0 (5.0-6.0), P=0.003 and pain, 5.5 (4.0-7.0), P=0.015. Future modifications to study methodology were identified, such as a longer period of wear and measurement of walking in different situations. CONCLUSIONS: This study confirmed the feasibility of a larger trial. It indicated differences in walking velocity and parameters concerning wear of the orthoses that could be explored further. A further crossover trial would require 27 participants in order to show a clinically meaningful difference in velocity of 0.13 ms(-1) with 90% power and alpha of 5%. PMID- 22089962 TI - Immediate effects of electrical stimulation combined with passive locomotion-like movement on gait velocity and spasticity in persons with hemiparetic stroke: a randomized controlled study. AB - OBJECTIVE: Research to examine the immediate effects of electrical stimulation combined with passive locomotion-like movement on gait velocity and spasticity. DESIGN: A single-masked, randomized controlled trial design. SUBJECTS: Twenty seven stroke inpatients in subacute phase (ischemic n = 16, hemorrhagic n = 11). INTERVENTIONS: A novel approach using electrical stimulation combined with passive locomotion-like movement. MAIN MEASURES: We assessed the maximum gait speed and modified Ashworth scale before and 20 minutes after the interventions. RESULTS: The gait velocity of the electrical stimulation combined with passive locomotion-like movement group showed the increase form 0.68 +/- 0.28 (mean +/- SD, unit: m) to 0.76 +/- 0.32 after the intervention. Both the electrical stimulation group and passive locomotion-like movement group also showed increases after the interventions (from 0.76 +/- 0.37 to 0.79 +/- 0.40, from 0.74 +/- 0.35 to 0.77 +/- 0.36, respectively). The gait velocity of the electrical stimulation combined with passive locomotion-like movement group differed significantly from those of the other groups (electrical stimulation combined with passive locomotion-like movement versus electrical stimulation: P = 0.049, electrical stimulation combined with passive locomotion-like movement versus passive locomotion-like movement: P = 0.025). Although there was no statistically significant difference in the modified Ashworth scale among the three groups, six of the nine subjects (66.6%) in the electrical stimulation combined with passive locomotion-like movement group showed improvement in the modified Ashworth scale score, while only three of the nine subjects (33.3%) in the electrical stimulation group and two of the nine subjects (22.2%) improved in the passive locomotion-like movement group. CONCLUSION: These findings suggest electrical stimulation combined with passive locomotion-like movement could improve gait velocity in stroke patients. PMID- 22089963 TI - Effect of simvastatin on the pharmacokinetics of anastrozole. AB - We have prospectively tested the effects of simvastatin on the pharmacokinetics of anastrozole and on estrogen concentrations in postmenopausal women with hormone receptor-positive breast cancer who were receiving adjuvant anastrozole. Following 14 days of simvastatin, we did not observe a significant change in plasma concentrations of anastrozole or hydroxyanastrozole in nine evaluable women. Likewise, we did not observe any statistically significant change in serum concentrations of either estradiol, which remained in the undetectable range, or estrone sulfate. Simvastatin and anastrozole may be safely co-administered. Pharmacokinetic results suggest that simvastatin is not likely to compromise the activity of anastrozole. PMID- 22089965 TI - Denbinobin, a phenanthrene from dendrobium nobile, inhibits invasion and induces apoptosis in SNU-484 human gastric cancer cells. AB - Dendrobium nobile is widely used as an analgesic, an antipyretic, and a tonic to nourish the stomach in traditional medicine. Mounting evidence suggests an antitumor activity of denbinobin, a major phenanthrene isolated from stems of Dendrobium nobile. The present study aimed to investigate the inhibitory effect of denbinobin on the invasive ability of human cancer cells. The cytotoxicity of denbonobin was examined in several human cancer cell lines including SK-Hep-1 hepato-carcinoma cells, SNU-484 gastric cancer cells, and HeLa cervix cancer cells. Because SNU-484 cells showed the lowest IC50 value, we examined the effect of denbinobin on the invasive ability of SNU-484 cells. The present study revealed, for the first time, that denbinobin inhibits the invasive phenotype of SNU-484 human gastric cancer cells in a dose-dependent manner. Expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were significantly decreased by denbinobin, suggesting that MMP-2/-9 may be responsible for the anti-invasive activity of denbinobin. We also provide evidence that denbinobin induces apoptosis through down-regulation of Bcl-2 and an up-regulation of Bax. Taken together, this study demonstrates that denbinobin inhibits invasion and induces apoptosis in highly invasive SNU-484 human gastric cancer cells. Given that gastric cancer has been estimated to be one of the most common causes of cancer related death among Asians and the major cause of death from gastric cancer is the metastatic spread of the disease, our findings may provide useful information regarding the application of denbinobin as a chemopreventive agent that could prevent or alleviate metastatic gastric cancer. PMID- 22089966 TI - Bacterial glyphosate resistance conferred by overexpression of an E. coli membrane efflux transporter. AB - Glyphosate herbicide-resistant crop plants, introduced commercially in 1994, now represent approximately 85% of the land area devoted to transgenic crops. Herbicide resistance in commercial glyphosate-resistant crops is due to expression of a variant form of a bacterial 5-enolpyruvylshikimate-3-phosphate synthase with a significantly decreased binding affinity for glyphosate at the target site of the enzyme. As a result of widespread and recurrent glyphosate use, often as the only herbicide used for weed management, increasing numbers of weedy species have evolved resistance to glyphosate. Weed resistance is most often due to changes in herbicide translocation patterns, presumed to be through the activity of an as yet unidentified membrane transporter in plants. To provide insight into glyphosate resistance mechanisms and identify a potential glyphosate transporter, we screened Escherichia coli genomic DNA for alternate sources of glyphosate resistance genes. Our search identified a single non-target gene that, when overexpressed in E. coli and Pseudomonas, confers high-level glyphosate resistance. The gene, yhhS, encodes a predicted membrane transporter of the major facilitator superfamily involved in drug efflux. We report here that an alternative mode of glyphosate resistance in E. coli is due to reduced accumulation of glyphosate in cells that overexpress this membrane transporter and discuss the implications for potential alternative resistance mechanisms in other organisms such as plants. PMID- 22089967 TI - Self-reported visual impairment among persons with diagnosed diabetes --- United States, 1997--2010. AB - Diabetes can lead to visual impairment (VI) and blindness (1). However, early detection and treatment of many common eye diseases, such as diabetic retinopathy and glaucoma, can reduce the risk for developing VI (1). Surveillance of VI among persons with diabetes is important for evaluating the effectiveness of efforts to reduce VI and other complications of diabetes. To examine trends in the prevalence of self-reported VI among adults (persons aged >=18 years) with diagnosed diabetes in the United States and to assess reported access to eye-care providers, CDC analyzed 1997-2010 data from the National Health Interview Survey (NHIS). This report describes the results of that analysis, which indicated that although the number of adults with diagnosed diabetes reporting VI increased, the age-adjusted percentage of adults with diagnosed diabetes who reported VI declined significantly, from 23.7% in 1997 to 16.7% in 2010. During this 14-year period, age-adjusted VI prevalence declined significantly among most categories of adults with diabetes: men, women, whites, Hispanics, those with some college or higher education, and those diagnosed with diabetes for >=3 years. Prevalence also declined among those aged >=45 years. The percentage of adults with diagnosed diabetes and self-reported VI who reported having consulted an eye-care provider in the past year remained constant at approximately 63%. Continued efforts are needed to sustain and improve the declining trends in self-reported VI and to increase rates of recommended eye examinations in the population with diabetes. PMID- 22089968 TI - Paralytic shellfish poisoning --- southeast Alaska, May--June 2011. AB - On June 6, 2011, the Section of Epidemiology (SOE) of the Alaska Division of Public Health was notified of a case of paralytic shellfish poisoning (PSP) in southeast Alaska. In collaboration with local partners, SOE investigated and identified a total of eight confirmed and 13 probable PSP cases that occurred during May--June 2011. Warnings to avoid noncommercially harvested shellfish were broadcast on local radio and television and displayed at beaches and in post offices, government offices, and businesses throughout the region. Commercially harvested shellfish, which are tested for the presence of PSP-causing toxins, were safe. Because the risk for PSP is unpredictable, persons who consume noncommercially harvested Alaskan shellfish should know that they are at risk for PSP, and suspected cases should be reported promptly to SOE to initiate control measures in the affected area. PMID- 22089969 TI - How ionic liquids can help to stabilize native proteins. AB - The native state of a globular protein is essential for its biocatalytic function, but is marginally stable against unfolding. While unfolding equilibria are often reversible, folding intermediates and misfolds can promote irreversible protein aggregation into amorphous precipitates or highly ordered amyloid states. Addition of ionic liquids-low-melting organic salts-offers intriguing prospects for stabilizing native proteins and their enzymatic function against these deactivating reaction channels. The huge number of cations and anions that form ionic liquids allows fine-tuning of their solvent properties, which offers robust and efficient strategies for solvent optimization. Going beyond case-by-case studies, this article aims at discussing principles for a rational design of ionic liquid-based formulations in protein chemistry and biocatalysis. PMID- 22089970 TI - Approval summary: letrozole (Femara(r) tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. AB - On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara(r); Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76-1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen. PMID- 22089971 TI - Selenium concentration and glutathione peroxidase (GSH-Px) activity in serum of cows at different stages of lactation. AB - The aim of the study was to evaluate the activity of glutathione peroxidase (GSH Px) and the concentration of selenium in Holstein-Friesian cows at different stages of lactation. Selenium was determined spectrofluorimetrically and GSH-Px activity using a Sigma CGP1 Glutathione Peroxidase Cellular Activity Assay kit. Mean serum selenium concentration was highest in early-lactation multiparous cows (0.18 MUg/ml) and the lowest in dry cows (0.111 MUg/ml). In early lactation, serum selenium concentration was significantly (P <= 0.01) higher in multiparous cows than in cows from the other groups. Mean GSH-Px activity in the serum of dry cows was over twice lower than in late-lactation cows (P <= 0.01) and over four times lower than in first-calving heifers and multiparous cows in early lactation (P <= 0.01). The coefficients of Spearman's rank correlation between GSH-Px activity and selenium concentration in the cows at different stages of lactation were not significant. A significant (P <= 0.01) mean positive correlation (0.46) was found between GSH-Px activity and serum selenium concentration for all the cows analysed together. The highest Se concentration and GSH-Px activity found in the serum of cows during the first stage of lactation may suggest that the generation of reactive oxygen species and their derivatives was higher during this period compared to the other stages, thus placing the cows at a greater risk of oxidative stress. It is therefore essential to give particular attention during this period to meeting the cows' requirement for selenium and other feed components that increase, directly or indirectly, the capacity of the body's antioxidant system. PMID- 22089972 TI - Reasons for lower transformation efficiency in indica rice using Agrobacterium tumefaciens-mediated transformation: lessons from transformation assays and genome-wide expression profiling. AB - Agrobacterium tumefaciens-mediated genetic transformation has been routinely used in rice for more than a decade. However, the transformation efficiency of the indica rice variety is still unsatisfactory and much lower than that of japonica cultivars. Further improvement on the transformation efficiency lies in the genetic manipulation of the plant itself, which requires a better understanding of the underlying process accounting for the susceptibility of plant cells to Agrobacterium infection as well as the identification of plant genes involved in the transformation process. In this study, transient and stable transformation assays using different japonica and indica cultivars showed that the lower transformation efficiency in indica rice was mainly due to the low efficiency in T-DNA integration into the plant genome. Analyses of the global gene expression patterns across the transformation process in different varieties revealed major differences in the expression of genes responding to Agrobacterium within the first 6 h after infection and more differentially expressed genes were observed in the indica cultivar Zhenshan 97 (ZS), with a number of genes repressed early during infection. Microarray analysis revealed an important effect of plant defense response on Agrobacterium-mediated transformation. It has been shown that some genes which may be necessary for the transformation process were down regulated in the indica cultivar ZS. This dataset provided a versatile resource for plant genomic research to understand the regulatory network of transformation process, and showed great promise for improving indica rice transformation using genetic manipulation of the rice genome. PMID- 22089974 TI - The first European journal on cardiac electrophysiology and pacing, the European Journal of Cardiac Pacing and Electrophysiology. PMID- 22089973 TI - A transcriptomic analysis reveals the nature of salinity tolerance of a wheat introgression line. AB - The bread wheat cultivar Shanrong No.3 (SR3) is a salinity tolerant derivative of an asymmetric somatic hybrid between cultivar Jinan 177 (JN177) and tall wheatgrass (Thinopyrum ponticum). To reveal some of the mechanisms underlying its elevated abiotic stress tolerance, both SR3 and JN177 were exposed to iso-osmotic NaCl and PEG stress, and the resulting gene expression was analysed using a customized microarray. Some genes associated with stress response proved to be more highly expressed in SR3 than in JN177 in non-stressed conditions. Its unsaturated fatty acid and flavonoid synthesis ability was also enhanced, and its pentose phosphate metabolism was more active than in JN177. These alterations in part accounted for the observed shift in the homeostasis related to reactive oxygen species (ROS). The specific down-regulation of certain ion transporters after a 0.5 h exposure to 340 mM NaCl demonstrated that Na(+) uptake occurred rapidly, so that the early phase of salinity stress imposes more than simply an osmotic stress. We discussed the possible effect of the introgression of new genetic materials in wheat genome on stress tolerance. PMID- 22089975 TI - Corneal perforation as a primary manifestation of keratoconus in a patient with underlying rheumatoid arthritis. AB - PURPOSE: The purpose of this study is to report a case of corneal perforation in a patient with undiagnosed keratoconus and underlying rheumatoid arthritis. METHODS: This is a retrospective case study based on the patient's medical records and followed by a brief review of the literature. RESULTS: A 53-year-old patient was referred to our department for acute pain and sudden decrease of visual acuity in his left eye. Corneal perforation was detected and attributed to a previously undiagnosed and untreated keratoconus. Additional laboratory work-up and clinical examination revealed a coexisting rheumatoid arthritis. Amniotic membrane was originally transplanted in order to maintain the structural integrity and promote healing of the perforated eye. Subsequently, the patient underwent a penetrating keratoplasty, though with unfavorable results due to postoperative endophthalmitis. CONCLUSIONS: Rheumatoid arthritis may be associated with higher risk of corneal perforation in patients with ectatic degenerative diseases such as keratoconus. PMID- 22089976 TI - Intravitreal bevacizumab as an adjunct to vitrectomy in advanced Eales' disease. AB - PURPOSE: This study aimed to report the use of intravitreal bevacizumab as an adjunctive treatment in two cases of advanced Eales' disease with vitreous haemorrhage and tractional retinal detachment, prior to vitreoretinal surgery. METHOD: In two patients presenting with vitreous haemorrhage, retinal neovascularisation and localised tractional retinal detachment, 1.25 mg of intravitreal bevacizumab was injected prior to vitrectomy, membrane peeling and endolaser photocoagulation of retina. RESULT: Regression of the retinal neovascularisation with resolution of dye leakage on fluoroscein angiography was observed in both cases. Membrane peeling could be performed with minimal bleeding during vitreoretinal surgery in both cases. CONCLUSION: Bevacizumab may be a possible adjunctive treatment to vitreoretinal surgery for the management of Eales' disease with tractional retinal detachment. PMID- 22089977 TI - Access to the ophthalmic artery by retrograde approach through the posterior communicating artery for intra-arterial chemotherapy of retinoblastoma. AB - Intra-arterial infusion of chemotherapy into the ophthalmic artery for treatment of retinoblastoma has been realized after catheterization of the internal carotid and temporary balloon occlusion beyond the orifice of the ophthalmic artery, or more recently after superselective canulation of the ophthalmic artery by a microcatheter. The superselective catheterization of the ophthalmic artery could be cumbersome because of the implantation of the ostium on the carotid siphon or because of the tortuosity of the carotid siphon. We report our experience of using a retrograde approach through the posterior communicating artery that allows a more direct angle of access to the origin of the ophthalmic artery. PMID- 22089978 TI - Information channels associated with awareness of human papillomavirus infections and vaccination among Latino immigrants from safety net clinics. AB - We report on information channels associated with awareness about human papillomavirus (HPV) among immigrant Central and South American Latinos. We conducted a survey of 1,334 Latino >= 21 years attending safety-net clinics in 2007-2008. Logistic regression analyses evaluated associations with HPV awareness. Forty-eight percent were aware of HPV infection and 40% were aware of the vaccine. Spanish television (38%) and providers (23%) were the primary HPV information sources. Infection awareness was associated with internet use (OR 1.47; 95% CI 1.10-1.96) and self-efficacy to find health information (OR 1.19; 95% CI 1.08-1.30). Vaccine awareness was associated with media use for health information (OR 1.27; 95% CI 1.09-1.49) and internet use (OR 1.59; 95% CI 1.18 2.13). Although Spanish television has reached this low HPV awareness group, there may be missed opportunities for education by providers. Television and the internet may also be effective channels for future interventions. PMID- 22089979 TI - Health risk behaviors among five Asian American subgroups in California: identifying intervention priorities. AB - This analysis assessed the prevalence of excess body weight, physical inactivity and alcohol and tobacco use in Asian American subgroups. Using 2005 California Health Interview Survey data, we estimated the prevalence of body mass index (BMI) categories using both standard and World Health Organization-proposed Asian specific categories, physical inactivity, and alcohol and tobacco use for Chinese (n = 1,285), Japanese (n = 421), Korean (n = 620), Filipino (n = 659) and Vietnamese (n = 480) Americans in California. About 80% of Japanese and Filipino American men and 70% of Korean American men were "increased/high risk" by Asian specific BMI categories. Most Asian American subgroups were more likely to walk for transportation than non-Hispanic whites, but less likely to report other physical activities. Highest smoking and binge drinking prevalences were among Korean, Vietnamese and Filipino American men and Japanese and Korean American women. These results suggest risk profiles for each Asian American subgroup to consider when setting priorities for health promotion programs. PMID- 22089980 TI - The association between self-reported symptoms of recent airway infection and CRP values in a general population. AB - C-reactive protein (CRP) is a much used biomarker for respiratory tract infection; however, the influence of airway infection on the CRP level in the general population has not been well described. The study aimed to evaluate the impact of recent symptoms of airway infection on the CRP level and how the predictive power of other known CRP predictors is influenced by taking respiratory symptoms into account. A total of 6,325 participants, aged 38-87 years, in the Tromso Study, a repeated population-based survey, were examined with questionnaires, measurements of height and weight, spirometry, and high sensitivity CRP analyses. The mean CRP value was 2.86 mg/L, and the geometric mean was 1.51 mg/L. Geometric means above 2.0 mg/L were found in the subgroups with the following characteristics: self-reported COPD, diabetes, recent symptoms of airway infection, forced expiratory volume in 1 s (FEV1) <80% predicted, body mass index (BMI) >=30, and subjects treated with inhaled or oral corticosteroids. Among the subjects who reported recent airway infection, 10.5% had a CRP value of >=10 mg/L, compared to 3.3% among the remaining participants. By multivariate analysis, BMI was the strongest independent predictor of the CRP level, followed by recent airway infection, FEV1% predicted, age, and current smoking. The study clearly demonstrates that a report of recent symptoms of airway infection strongly predicts the CRP level in the population. Such symptoms were shared rather equally between subgroups with increased CRP level, and the risk of being an important confounder in epidemiological studies is probably low. In the clinical setting, care should be taken when using the CRP level as a guide for medical prevention of chronic diseases. PMID- 22089981 TI - Sleep deprivation and postpartum mental health: case report. PMID- 22089982 TI - Short Psychological Intervention as a Perioperative Pain Reduction Treatment in Spinal Neurosurgery. AB - STUDY AIMS: The aim of the present pilot study was to test the feasibility of an innovative Short Psychological Intervention (SPI) for back pain patients as part of an acute inpatient neurosurgical treatment. Fear and fear-avoidance beliefs have been shown to influence the functional outcome in chronic back pain (CBP) patients. Therefore, a reduction of fear and fear-avoidance beliefs should improve the functional outcome and reduce pain in the acute neurosurgical setting. PATIENTS AND METHODS: 39 patients were studied in a randomized prospective longitudinal study. The patients had severe degenerative spinal disease and had undergone posterior lumbar interbody fusion. RESULTS: All patients enrolled in the study were investigated in the immediate preoperative period and 6 weeks postoperatively using a package of standardized questionnaires in which pain intensity, fear-avoidance beliefs, and physical fitness were recorded. In 19 of the patients, the surgical procedure was supplemented by a SPI based on methods to increase self-efficacy by reducing fear-avoidance beliefs. While the intervention group reported a significantly greater reduction in the highest pain intensity and a better physical fitness compared to the control group, we did not find a significant decrease in fear-avoidance beliefs in the intervention group at the second time of assessment, possibly due to the relatively small sample size. CONCLUSIONS: The study confirmed that psychological interventions can offer significant benefits when used in the acute inpatient setting as the outcome of surgery can be positively influenced. Future studies should focus on cost savings related to improved postoperative recovery and a possible reduction of chronic postoperative pain. PMID- 22089983 TI - Is ICRP guidance on the use of reference levels consistent? AB - In ICRP 103, which has replaced ICRP 60, it is stated that no fundamental changes have been introduced compared with ICRP 60. This is true except that the application of reference levels in emergency and existing exposure situations seems to be applied inconsistently, and also in the related publications ICRP 109 and ICRP 111. ICRP 103 emphasises that focus should be on the residual doses after the implementation of protection strategies in emergency and existing exposure situations. If possible, the result of an optimised protection strategy should bring the residual dose below the reference level. Thus the reference level represents the maximum acceptable residual dose after an optimised protection strategy has been implemented. It is not an 'off-the-shelf item' that can be set free of the prevailing situation. It should be determined as part of the process of optimising the protection strategy. If not, protection would be sub-optimised. However, in ICRP 103 some inconsistent concepts have been introduced, e.g. in paragraph 279 which states: 'All exposures above or below the reference level should be subject to optimisation of protection, and particular attention should be given to exposures above the reference level'. If, in fact, all exposures above and below reference levels are subject to the process of optimisation, reference levels appear superfluous. It could be considered that if optimisation of protection below a fixed reference level is necessary, then the reference level has been set too high at the outset. Up until the last phase of the preparation of ICRP 103 the concept of a dose constraint was recommended to constrain the optimisation of protection in all types of exposure situations. In the final phase, the term 'dose constraint' was changed to 'reference level' for emergency and existing exposure situations. However, it seems as if in ICRP 103 it was not fully recognised that dose constraints and reference levels are conceptually different. The use of reference levels in radiological protection is reviewed. It is concluded that the recommendations in ICRP 103 and related ICRP publications seem to be inconsistent regarding the use of reference levels in existing and emergency exposure situations. PMID- 22089984 TI - Photolithographic surface micromachining of polydimethylsiloxane (PDMS). AB - A major technical hurdle in microfluidics is the difficulty in achieving high fidelity lithographic patterning on polydimethylsiloxane (PDMS). Here, we report a simple yet highly precise and repeatable PDMS surface micromachining method using direct photolithography followed by reactive ion etching (RIE). Our method to achieve surface patterning of PDMS applied an O(2) plasma treatment to PDMS to activate its surface to overcome the challenge of poor photoresist adhesion on PDMS for photolithography. Our photolithographic PDMS surface micromachining technique is compatible with conventional soft lithography techniques and other silicon-based surface and bulk micromachining methods. To illustrate the general application of our method, we demonstrated fabrication of large microfiltration membranes and free-standing beam structures in PDMS. PMID- 22089985 TI - Behcet disease: clinical features and management in a Brazilian tertiary hospital. AB - BACKGROUND: Behcet disease (BD) is prevalent in Central and East Asia and in the Eastern Mediterranean area where most studies have been performed. Few studies have evaluated patients with BD in Brazil. OBJECTIVES: The objective of the study was to describe clinical manifestations of BD and their therapy in a single center in Brazil. METHODS: Sixty patients who met the International Study Group Criteria for BD and were under follow-up at the Vasculitis Unit of the Universidade Federal de Sao Paulo were evaluated in a retrospective observational study. RESULTS: Mean age at study was 40.0 (SD, 10.7) years, and the female-male ratio was 1.2:1.0. The frequency of disease manifestations was as follows: oral ulcers, 100%; genital ulcers, 93.3%; ocular manifestations, 63.3%; arthritis, 46.7%; cutaneous lesions, 71.7%; positive pathergy test, 22.7%; neurologic involvement, 28.3%; thrombosis, 13.3%; and gastrointestinal involvement, 3.3%. Arthritis and erythema nodosum were more prevalent among women, whereas papulopustular lesions were more common in men. The frequency of each treatment modality was as follows: colchicine, 78.3%; thalidomide, 26.7%; colchicine and penicillin, 21.7%; dapsone, 8.3%; and pentoxyphyline, 8.3%. These treatments were mainly used for mucocutaneous manifestations. Immunosuppressive drugs were prescribed for 70% of the patients, including azathioprine (35.0%), cyclophosphamide (28.3%), cyclosporin A (21.7%), methotrexate (18.3%), and chlorambucil (6.7%). Infliximab was used in 5.0% of refractory patients. No differences were observed between sexes related to severe manifestations of BD. CONCLUSIONS: Although reported elsewhere, Brazilian men with BD did not have a worse prognosis. Women had a higher frequency of arthritis manifestations. PMID- 22089986 TI - Immunoglobulin G4-related disease with lymphoplasmacytic aortitis mimicking Takayasu arteritis. PMID- 22089987 TI - Adult-onset Still disease in a patient with acute hepatitis A. PMID- 22089988 TI - Antiphospholipid antibodies in malignancy: are these pathogenic or epiphenomena? AB - Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by arterial and venous thrombotic events associated with antiphospholipid antibodies. Antiphospholipid syndrome is commonly seen with collagen vascular diseases; however, other entities that can cause APS include chronic viral infections, certain medications, and malignancies. We present an interesting patient with an atypical presentation and course of presumed APS, which lead us to perform an exhaustive search for a secondary cause. The patient was ultimately found to have splenic marginal zone lymphoma. Analysis of the current data in the literature is presented for APS, antiphospholipid antibodies, and malignancy. Based on the literature findings and our experience, we recommend a thorough and repeated evaluation for an underlying malignancy in patients who have an atypical presentation and features of APS. PMID- 22089989 TI - Cutaneous necrosis as a presenting manifestation of antiphospholipid antibodies. PMID- 22089990 TI - Psychological status in Moroccan patients with ankylosing spondylitis and its relationships with disease parameters and quality of life. AB - BACKGROUND: The evaluation of emotional status is an important parameter in management of rheumatic diseases. There are few studies evaluating the psychological status in ankylosing spondylitis (AS) and its relationships with disease parameters and quality of life. OBJECTIVE: In this study, we evaluated the psychological status in Moroccan patients with AS and its relationships with the activity of the disease, the functional status, and the quality of life. PATIENTS: One hundred ten patients were included in this cross-sectional study according to the modified New York criteria for AS. Psychological status was assessed by the Hospital Anxiety and Depression Scale (HADS) including the depression and anxiety subscales. The quality of life was evaluated by the Short Form 36. RESULTS: Depression was found in 55.5% and anxiety in 60% among our patients. The HADS depression and anxiety subscales were significantly correlated with clinical parameters and with worsening in all domains of the Short Form 36.Multivariate logistic regression analysis revealed that role limitations due to emotional problems, vitality, and general health perception were independent risk factors of anxiety. The Bath Ankylosing Spondylitis Functional Index, vitality, and role limitations due to emotional problems were the independent factors that influenced the risk of depression. CONCLUSION: This study suggests that depression and anxiety are frequent in AS. Impaired quality of life and functional disability seemed to be independent risk factors of psychological disorders. Therefore, assessment and management of patients with AS should take into account the evaluation and management of their psychological disorders and improvement of their functional disability. PMID- 22089991 TI - A randomized controlled trial evaluating the cost-effectiveness of sonographic guidance for intra-articular injection of the osteoarthritic knee. AB - OBJECTIVE: The present randomized controlled study investigated whether sonographic needle guidance affected the outcomes of intra-articular injection for osteoarthritis of the knee. METHODS: Ninety-four noneffusive knees with osteoarthritis were randomized to injection by conventional palpation-guided anatomic landmark injection or sonographic image-guided injection enhanced with a 1-handed mechanical (the reciprocating procedure device) syringe. After intra articular placement and synovial space dilation were confirmed by sonography, a syringe exchange was performed, and 80 mg of triamcinolone acetonide was injected with the second syringe through the indwelling intra-articular needle. Baseline pain, procedural pain, pain at outcome (2 weeks and 6 months), responders, therapeutic duration, reinjection rates, total cost, and cost per responder were determined. RESULTS: Relative to conventional palpation-guided anatomic landmark methods, sonographic guidance for injection of the knee resulted in 48% reduction in procedural pain (P < 0.001), a 42% reduction in pain scores at outcome (P < 0.03), 107% increase in the responder rate (P < 0.001), 52% reduction in the nonresponder rate (P < 0.001), a 36% increase in therapeutic duration (P = 0.01), a 13% reduction ($17) in cost per patient per year, and a 58% ($224) reduction in cost per responder per year for a hospital outpatient (P < 0.001). CONCLUSIONS: Sonographic needle guidance reduced procedural pain and improved the clinical outcomes and cost-effectiveness of intra-articular injections of the osteoarthritic knee. PMID- 22089992 TI - Anti-cyclic citrullinated peptide antibodies in adult patients with juvenile idiopathic arthritis. AB - BACKGROUND: Antibodies to cyclic citrullinated peptide (anti-CCP) have been found in different proportions in the juvenile idiopathic arthritis (JIA) population. The majority of studies have been done in children or mixed population (children plus adults). AIM: The objective of the study was to study the prevalence of anti CCP in JIA adult patients. METHODS: Anti-CCP3 was searched for in 49 adult patients with JIA and associated with clinical and demographics data. As comparisons, 156 patients with adult rheumatoid arthritis (RA) and 100 healthy volunteers were studied. RESULTS: Nine patients (18.3%) were positive for anti CCP3. All of them had the polyarthritis form. This antibody was more common in JIA than in control subjects (P = 0.0002) and less common in JIA than in adult RA patients (P < 0.0001), but the rheumatoid factor polyarticular form of JIA had the same prevalence as in adult RA patients (P = 0.33).In JIA patients, anti-CCP had a positive association with the presence of rheumatoid factor (P < 0.0001), worse functional status (P = 0.04), need for orthopedic surgery (P = 0.01), and later disease onset (P = 0.0007). CONCLUSIONS: In adult patients with JIA, the prevalence of anti-CCP3 is 18%, and its presence may define a sample of patients with worse prognosis. PMID- 22089993 TI - Spontaneous resolution of apparent radiation associated retroperitoneal fibrosis. AB - A 70-year-old man was diagnosed with retroperitoneal fibrosis (RPF) complicated by ureteral obstruction 4 months after finishing radiotherapy for prostate cancer. He was treated conservatively with ureteral stent placement. After 3 months, computed tomography scan of the abdomen revealed resolution of RPF without any medical or surgical interventions. Although an uncommon event, the possibility of spontaneous resolution of RPF, as demonstrated by this and previously reported cases, has led some to encourage conservative management. PMID- 22089995 TI - Life-threatening hepatitis C virus-associated polyarteritis nodosa successfully treated by rituximab. AB - By contrast to cryoglobulinemic vasculitis, polyarteritis nodosa associated with hepatitis C virus (HCV) infection is rare and still a controversial entity. The best treatment for this condition is not established. Cases reported in the literature have been treated with various combinations of corticosteroids, antiviral therapy, and immunosuppressants. We report a case of severe life threatening HCV-associated polyarteritis nodosa successfully treated with rituximab and a short course of corticosteroids without antiviral therapy. This case, along with recently published data, emphasizes the value of B-cell-targeted therapy in this unusual form of HCV-associated vasculitis. PMID- 22089994 TI - Leprosy initially misdiagnosed as sarcoidosis, adult-onset still disease, or autoinflammatory disease. AB - Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. We describe the case of a 20-year-old man from India living in Italy since 2003, who presented with erythematous papules and nodules distributed on his arms, legs, and face in 2006. He also had episodes of high fever, polyarthritis, and episcleritis. Sarcoidosis was suspected on the basis of elevated angiotensin converting enzyme and bronchoalveolar lavage fluid, and the patient was treated with corticosteroids for about a year. A flare of the disease occurred each time corticosteroid was tapered or suspended. An autoinflammatory disease was then suspected and treated with immunosuppressant. Only the third deep skin biopsy revealed the presence of M. leprae. The lack of clinical suspicion and the unfamiliarity with the histology of leprosy delayed diagnosis and treatment. Leprosy should be considered in the differential diagnoses of patients presenting with rheumatic and cutaneous manifestations especially when they come from countries where the disease is endemic. PMID- 22089996 TI - Parvovirus B19-associated arthritis: report on a community outbreak. PMID- 22089997 TI - Granulomatosis with polyangiitis (Wegener's) presenting as a periaortic mass. PMID- 22089998 TI - Establishment of a Chinook salmon cell line with an inducible gene expression system. AB - We have isolated a stable recombinant cell line CHSE-TOF5 derived from the Chinook salmon (Oncorhynchus tshawytscha) embryo cells for use as an inducible expression system. The cells were transfected with the pTet-Off plasmid from the Tet On/Off Clontech system, carrying a G418 resistance gene. Several G418 resistant clones were subcultured and characterised by quantitative PCR (qPCR) and by transient transfection. The level of expression of transcriptional activator was measured by qPCR in a number of isolated clones, and transient transfection with a pTRE2-hyg-LUC plasmid was used to evaluate the inducibility of these clones. A clone was selected for its relative fast cell growth and good level of inducibility. This genetically engineered cell line is a valuable tool for the fish research community especially in research areas investigating the biological function of proteins from fish or fish pathogens. PMID- 22089999 TI - Microsurgical skills training with a new tympanoplasty model: learning curve and motivational impact. AB - OBJECTIVES: To evaluate the microsurgical skills training on a tympanoplasty model with regard to the learning curve and the participants' motivation for a surgical specialty. STUDY DESIGN: Randomized controlled prospective study. SETTING: Department of Otolaryngology, Head and Neck Surgery, Medical Campus Carl Gustav Carus at the Technische Universitat Dresden, Germany. SUBJECTS: Thirty randomly chosen fifth-year medical students divided into 2 groups. INTERVENTIONS: Group 2 (n = 16) had to perform an ossicular and tympanic membrane reconstruction on a tympanoplasty model on Days 1, 7, 14, and 21 and Group 1 (n = 14) on Days 1 and 21, while observing the procedure at Days 7 and 14. Six otosurgeons served as gold standard. Attempts and time of prosthesis placement and time for tympanic membrane reconstruction were recorded. Tremor frequency and amplitude were obtained at the same time points. An adjusted study interest questionnaire was used to assess students' motivation. RESULTS: Students in Group 2 showed a significant improvement in all reconstruction parameters over the study period compared with both, baseline measurement on first day and Group 1. However, the obtained learning curve did not reach the experts level. Tremor indices and students' motivation showed no correlation with the reconstruction parameters, whereas the training itself had a positive impact on students' interest in the surgical specialty. CONCLUSION: Training with the tympanoplasty model is suitable to acquire first microsurgical motor skills in otolaryngology and to arouse students' interest in the surgical field and otorhinolaryngology. PMID- 22090000 TI - A head shake sensory organization test to improve the sensitivity of the sensory organization test in the elderly. AB - OBJECTIVE: The head shake sensory organization test (HS-SOT) is an expansion of the sensory organization test (SOT), which evaluates impairment of the patient's ability to apply vestibular input while actively moving the head. HS-SOTs has been proposed to increase the sensitivity of SOTs. The purpose of this study was to investigate the value of HS-SOTs in a healthy population with respect to age and compare the sensitivity of HS-SOTs with that of SOTs in the elderly population. METHODS: One hundred two (n = 102) healthy subjects were divided into 3 age groups: the young adult group (between 20 and 39 yr), the adult group (between 40 and 59 yr), and the elderly group (between 60 and 79 yr). The subjects underwent SOTs and HS-SOTs. RESULTS: The equilibrium scores of HS-SOTs underwent more significant change than those of SOTs in the elderly group. The equilibrium score ratio SOT2/HS-SOT2 (HS-SOT during SOT condition 2) decreased by 4% more in the elderly group compared with that of the young adult group. The ratio of SOT5/HS-SOT5 decreased by 54% more in the elderly group compared with that of the young adult group. CONCLUSION: In the elderly, equilibrium scores of HS-SOTs changed more than those of SOTs. In addition, SOT5/HS-SOT5 demonstrated more sensitive changes in the elderly than SOT2/HS-SOT2 did. PMID- 22090001 TI - Results with cochlear implantation in adults with speech recognition scores exceeding current criteria. AB - OBJECTIVES: The primary purpose of this study was to evaluate a group of postlingually deafened adults, whose aided speech recognition exceeded commonly accepted candidacy criteria for implantation. The study aimed to define performance and qualitative outcomes of cochlear implants in these individuals compared with their optimally fitted hearing aid(s). STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: All postlingually deafened subjects (N = 27), who were unsuccessful hearing aid users implanted between 2000 and 2010 with a preimplantation Hearing in Noise Test (HINT) score of 60% or more were included. INTERVENTION: We compared patients' preoperative performance (HINT score) with hearing aids to postoperative performance with the cochlear implant after 12 months of device use. In addition, the Hearing Handicap Inventory questionnaire was used to quantify the hearing-related handicap change perceived after the implantation. RESULTS: The study group demonstrated significant postoperative improvement on all outcome measures; most notably, the mean HINT score improved from 68.4% (standard deviation, 8.3) to 91.9% (standard deviation, 9.7). Additionally, there was a significant improvement in hearing related handicap perceived by all patients. CONCLUSION: The envelope of implantation candidacy criteria continues to expand as shown by this study's cohort. Patient satisfaction and speech recognition results are very encouraging in support of treating those who currently perform at a level above the conventional candidacy threshold but struggle with optimally fitted hearing aids. PMID- 22090002 TI - Seborrheic keratosis of the external auditory canal. PMID- 22090003 TI - Front squat data reproducibility collected with a triple-axis accelerometer. AB - The purpose of our study was to assess data reproducibility from 2 consecutive front squat workouts, spaced 1 week apart, performed by American college football players (n = 18) as they prepared for their competitive season. For each workout, our methods entailed the performance of 3-6 front squat repetitions per set at 55, 65, and 75% of subject's 1 repetition maximum (1RM) load. In addition, a fourth set was done at a heavier load, with a resistance equal to 80 and 83% of their 1RM values, for the first and second workouts, respectively. A triple-axis accelerometer was affixed to a barbell to quantify exercise performance. Per load, the accelerometer measures peak values for the following indices: force, velocity, and power. To assess data reproducibility, inter-workout comparisons were made for 12 performance indices with 4 statistical test-retest measures: intraclass correlation coefficients, coefficients of variation (CVs), and the SEM expressed in both absolute and relative terms. Current results show that the majority of performance indices exceeded intraclass correlation (0.75-0.80) and CV (10-15%) values previously deemed as acceptable levels of data reproducibility. The 2 indices with the greatest variability were power and velocity values obtained at 55% of the 1RM load; thus, it was concluded that higher movement rates at the lightest load were the most difficult aspect of front squat performance to repeat successfully over time. Our practical applications imply lighter loads, with inherently higher rates of barbell movement, yield lower data reproducibility values. PMID- 22090004 TI - Anthropometry as a predictor of vertical jump heights derived from an instrumented platform. AB - The current study purpose examined the vertical height-anthropometry relationship with jump data obtained from an instrumented platform. Our methods required college-aged (n = 177) subjects to make 3 visits to our laboratory to measure the following anthropometric variables: height, body mass, upper arm length (UAL), lower arm length, upper leg length, and lower leg length. Per jump, maximum height was measured in 3 ways: from the subjects' takeoff, hang times, and as they landed on the platform. Standard multivariate regression assessed how well anthropometry predicted the criterion variance per gender (men, women, pooled) and jump height method (takeoff, hang time, landing) combination. Z-scores indicated that small amounts of the total data were outliers. The results showed that the majority of outliers were from jump heights calculated as women landed on the platform. With the genders pooled, anthropometry predicted a significant (p < 0.05) amount of variance from jump heights calculated from both takeoff and hang time. The anthropometry-vertical jump relationship was not significant from heights calculated as subjects landed on the platform, likely due to the female outliers. Yet anthropometric data of men did predict a significant amount of variance from heights calculated when they landed on the platform; univariate correlations of men's data revealed that UAL was the best predictor. It was concluded that the large sample of men's data led to greater data heterogeneity and a higher univariate correlation. Because of our sample size and data heterogeneity, practical applications suggest that coaches may find our results best predict performance for a variety of college-aged athletes and vertical jump enthusiasts. PMID- 22090005 TI - Evaluating hand in systemic sclerosis. AB - Articular symptoms are common in SSc and joint pain is a frequent presenting feature of this disease. Hand involvement is often the first clinical manifestation of SSc and could be resulted from fibrosis or synovitis or an overlap syndrome with rheumatoid arthritis (RA); though, the latter is a controversy in practice. To define the clues when identifying the nature of the hand arthropathy in SSc. In order to determine the hand arthropathy, serological tests, hand radiography, finger-to-palm (FTP) distance and other clinical features, disease activity and functional scoring parameters were assessed. Twenty-eight consecutive SSc patients and 43 controls (21 rheumatoid arthritis and 22 healthy controls) were included. Radiographic findings in SSc patients were: Erosions 25%, joint space narrowing 17.9%, arthritis 10.7%, radiological demineralisation 42.9%, acro-osteolysis 25%, flexion contracture 28.6% and calcinosis 17.9%. Anti-CCP antibody and RF positivity were as follows: In SSc group: 3 (11%) and 7 patients (25%); In RA group: 13 (62%) and 19 patients (90.5%); In healthy control group: 1 (4%) and 3 persons (13.6%), respectively. Two patients (7.14%) were regarded as RA overlap, whom both had positive RF and positive anti-CCP results and their radiographs revealed arthritis. Seventeen patients (61%) were regarded as SSc arthropathy; all were negative for RF and anti-CCP but revealed nonarthritic radiological findings. (Among them, only one patient had positive anti-CCP result). The remainder (9 patients) had no radiological or serological finding positive for arthropathy. Arthritis was found to have correlation with heart involvement and FTP was correlated with lung involvement. Hand involvement in SSc is a challenge in rheumatology practice; Radiographic testing when evaluated with RF and anti-CCP will be a helpful tool to discriminate SSc arthropathy from RA-SSc overlap. Hand arthropathy should increase the interest in the serious internal organ involvements of SSc. PMID- 22090006 TI - Successful treatment for conventional treatment-resistant dermatomyositis associated interstitial lung disease with adalimumab. AB - Dermatomyositis (DM) is a systemic autoimmune disorder characterized by the inflammation of skeletal muscles and pathognomonic skin rashes, namely heliotrope rash and Gottron's papules and involvement of other organs. Interstitial lung disease (ILD) seems to be one of the most characteristic manifestations of the lung and associated with increased morbidity and mortality in patients with DM. Despite DM-associated ILD requires aggressive therapy with cytotoxic agents, the efficacy is questionable in some cases, and more effective and less toxic therapies are needed. Recently, although there have been several reports of successful treatment of refractory case of PM and DM with the TNF-alpha antagonists, including infliximab and etanercept, there was no enough evidence for DM-associated ILD. We described herein a patient with DM-associated ILD who had poor response to conventional therapies and successfully treated with adalimumab. PMID- 22090007 TI - The role of interleukin-23/interleukin-17 axis in the development of systemic lupus erythematosus among patients with tuberculosis: comment on: Lin YC, Liang SJ, Liu YH et al.: tuberculosis as a risk factor for systemic lupus erythematosus: results of a nationwide study in Taiwan. (Rheumatol Int. 2011 Mar 18. [Epub ahead of print]). PMID- 22090008 TI - Living with scleroderma: patients' perspectives, a phenomenological study. AB - In this study, it is aimed to determine the daily life experiences of patients on the basis their own way of statement. Sixteen patients with scleroderma were enrolled to this qualitative study. Data were collected using both a demographic data form and a semi-structured interview form. Study was made on individual patient interview by face-to-face manner. Data were evaluated using Colaizzi's phenomenological data analysis method. Data analysis revealed four categories and nine topics. These categories were (1) physical impact of disease, (2) emotional impact of disease, (3) social impact of disease and (4) patient behaviours for the cope with the disease. As emotional impact, patients imply that they have experienced disappointment, hope to get well and have fears about the future. In the physical impact category, tight skin, limitations of hand skills, swelling of the hands and feet, fatigue, swallowing difficulties and deformation of their bodies were the prominent features. In patients with recognizable disease, difficulty to join to social activities increases and eventually leads to isolation. There was also some evidence that patients who have been supported by their family and close relatives seem to be more optimistic about their disease. Most patients are not willing to communicate with other patients, particularly in an advanced stage. Scleroderma patients imply that they experience several difficulties regarding emotional, physical and social aspects. Individual abilities to cope with the disease were much more improved among patients who have a sustained social support. For advanced patients with apparent deformations, an effective social support system should be introduced. PMID- 22090009 TI - Bucillamine-induced yellow nail in Japanese patients with rheumatoid arthritis: two case reports and a review of 36 reported cases. AB - Yellow nail syndrome is an idiopathic condition characterized by a triad consisting of yellow nail, lymphedema, and pulmonary manifestations. Thiol compounds such as D-penicillamine have been reported to be the major cause of drug-induced yellow nail syndrome in patients with rheumatoid arthritis (RA). We recently experienced two Japanese cases with RA who developed yellow nail under treatment with bucillamine, a thiol-containing anti-rheumatic drug developed and approved in Japan. We reviewed the literature for similar cases and identified 36 RA cases with bucillamine-induced yellow nail, mostly in Japanese medical journals. Most of these cases (90.3%) showed improvement of yellow nail after discontinuation of bucillamine, whereas lymphedema and pulmonary manifestations improved only in 30.8 and 35.0% of the patients, respectively. PMID- 22090010 TI - Paraneoplastic rheumatic syndromes: report of eight cases and review of literature. AB - Malignant neoplasms are associated with a wide variety of paraneoplastic rheumatological syndromes. The paraneoplastic nature should be based on specific criteria. We report a series of eight cases of paraneoplastic rheumatic syndromes revealing an underlying neoplasia. Our series consists of six men and two women, with a mean age of 46.1 (20-69 years). The first case is a hypertrophic osteoarthropathy of Pierre Marie that occurred in a 20-year-old man 1 month after treatment for his nasopharyngeal carcinoma; the paraclinical examinations showed lung and bone metastasis. The second case is that of a bilateral shoulder-hand syndrome revealing an invasive squamous cell carcinoma of the cervix in a 63-year old woman. The third case involved a 69-year-old patient who had surgery 2 years ago for prostate adenocarcinoma and presented with polymyalgia rheumatica revealing bone metastasis. We also report two cases of leukemia in adults revealed by polyarthritis. The sixth observation is that of a paraneoplastic scleroderma that occurred concomitantly with prostate cancer. The seventh case of an acute arthritis showed a B lymphoma. The eighth case is that of a 52-year-old patient who presented with inflammatory arthralgias, and digital clubbing revealing a squamous cell carcinoma of the skin. Paraneoplastic rheumatism remains a rare event, but knowledge of it is essential for early diagnosis of underlying cancer. PMID- 22090011 TI - In vivo animal models of spinal metastasis. AB - The vertebral column is the commonest site for skeletal metastases, with breast, prostate and lung cancers being the most common primary sources. The spine has structural and neural-protective properties thus involvement by metastatic cancer often causes bony instability and fracture, intractable pain and neurological deficit. In vivo animal models which resemble the human condition are essential in order to improve understanding of the pathophysiology behind the spread of metastatic cancer to the spine and its subsequent local growth and invasion, to enable in-depth analysis of the interaction between host and tumour cells and the molecular processes behind local cancer invasion and barriers to invasion as well as to allow assessment of novel treatment modalities for spinal metastases. This review summarizes the current status of the animal models specifically used for the study of spinal metastasis, their relevance, advantages and limitations, and important considerations for the development of future in vivo animal models. PMID- 22090012 TI - [Evidence-based surgery. What is really verified?]. PMID- 22090013 TI - [Lymphadenectomy for malignancies of the upper gastrointestinal tract]. AB - Studies from specialized and high volume centers revealed an improved overall survival for patients subjected to extended lymphadenectomy. The drawbacks of radical lymph node dissection seem to be represented in higher rates of morbidity and mortality and thus are correlated to the surgical expertise of the respective institution. Especially patients in the early stages of metastatic lymph node spread benefit from extended and more radical lymphadenectomy. In a retrospective analysis of this institution's own patients, a pN0 category pT stage and the amount of retrieved lymph nodes have been found to be independent prognostic factors. In patients with up to six positive nodes (pN1) pT stage, the number of retrieved nodes, the number of positive nodes and R stage are correlated to survival prognosis. If more than six nodes are invaded only the amount of metastatic nodes and R stage are relevant prognostic factors. It will be of upmost interest to compare these data with analyses from regional and national cancer registers for gastric and esophageal cancer. As so far no reliable procedure for preoperative determination of lymphatic spread exists, the recommendations by the respective research organizations will have to be adopted until further notice, which is D2 lymphadenectomy for locally advanced gastric cancer and 2-field lymphadenectomy for patients with advanced esophageal cancer.Due to higher complication rates for patients subjected to radical lymphadenectomy, it is recommended that these procedures be performed in specialized high volume centers with corresponding surgical experience. PMID- 22090014 TI - [Lymph node dissection for carcinomas of the lower gastrointestinal tract. What is evidence-based?]. AB - Evidence-based analysis of the influence of lymph node dissection on the prognosis of colorectal cancer patients is complicated by the now well established multimodal treatment strategies. In addition surgical quality criteria, such as exact preparation along the mesenterial fascia and avoiding tears have a major influence on the prognosis.Nevertheless, the overall evidence for the need of lymph node dissection in the treatment of colorectal carcinoma is high. However, there are still some questions remaining concerning the extent of pericolic lymph node dissection, inclusion of the lymph nodes along the greater curvature of the stomach and the inferior aspect of the left pancreas in carcinomas of the transverse colon and the flexures. In particular the definitive central ligation of the supplying arteries in right-sided colon carcinoma is not adequately implemented worldwide. PMID- 22090015 TI - [Thrombosis prophylaxis in surgery. What is the evidence?]. AB - Prevention of venous thromboembolism has become routine in all surgical disciplines and consists of physical and pharmacological measures. The indications and choice of prophylaxis modality depend on the individual patient risk profile which is determined by the combination of exposing and predisposing risk factors. The exposing risk factors are characterized by the type and extent of surgery or trauma, whereas the predisposing risk factors relate to patient inherent risk factors. This is also taken into consideration for the compilation of guidelines. This review summarizes the recommendations of the German S3 guidelines related to surgery and also discusses the perioperative management of patients receiving long-term anticoagulation with new oral anticoagulants (rivaroxaban, apixaban, dabigatran). PMID- 22090016 TI - [Contribution of the Study Center of the German Surgical Society to evidence based surgery]. AB - Since the Study Center of the German Surgical Society (SDGC) was established in 2003 it has been supporting surgeons to implement their ideas for multicenter randomized studies. Assistance is provided for development (sample size calculation, protocol, funding application) implementation (submission to ethics committee, data management, monitoring) and analysis (statistical analysis, publication) in close collaboration with biometricians and data managers. Currently more than 2,500 patients have been included in 11 trials. The most complex SDGC study (SYNCHRONOUS) so far with up to 80 participating centers has been activated in September 2011. Furthermore, there is an increasing relevance for systematic reviews and meta analyses with regard to the development of studies and aggregation of results. For this reason a systematic review working group was established within the SDGC. To date 13 publications have been completed and 8 more are underway. PMID- 22090017 TI - [Update gastric surgery. Are innovations really always better?]. PMID- 22090018 TI - [The new TNM classification of tumors of the esophagogastric junction. Surgical consequences]. AB - The new International Union Against Cancer (UICC) classification in its seventh version has been out since January 2010. It included some important changes for the classification of esophageal and gastric carcinomas compared to the sixth version. For esophageal carcinomas this means a more detailed subdivision of the T and N stages which should, together with the newly introduced prognostic grouping (separate for squamous cell carcinoma and adenocarcinoma) enable a more precise and individualized prediction of prognosis. Another innovation is that positive lymph nodes in the esophageal drainage area, including celiac axis nodes and paraesophageal lymph nodes in the neck, are classified as regional lymph node metastases rather than distant metastatic spread, irrespective of tumor location. Hereby the lymphadenectomy specimen should include >= 6 lymph nodes (LN). The most controversial improvement is that adenocarcinomas of the esophagogastric junction (AEG) are all classified as esophageal carcinomas. This should acknowledge the similar prognosis of AEGs and esophageal carcinomas, which is worse compared to gastric carcinomas in other locations. Regarding the classification of gastric carcinomas the T-stages were redefined and lymph node staging (N-stage) was refined to allow for a better prediction of prognosis. The lymphadenectomy specimen after gastrectomy should hereby include >= 16 LNs. As the primary aim of the UICC classification is a preferably accurate prognosis prediction, the impact on a surgeon's therapeutic decision is low. For decisions regarding the type of resection the endoscopic AEG classification with the aim of R0 resections is still the instrument of choice. The value of the UICC classification is that it enables sophisticated comparisons between different treatment regimens and strategies. PMID- 22090019 TI - [Endoscopic therapy in early gastric cancer]. AB - Endoscopic treatment of early gastric cancer has been shown to be effective and safe. It is a minimally invasive and organ-preserving treatment approach that can safely be used as an alternative to surgical resection. A prerequisite of any endoscopic treatment with a curative intent is a very low risk of lymph node metastasis of the lesion intended to be endoscopically resected. As in high volume surgical centers all endoscopic procedures with a curative intent should also be carried out in centers with a high expertise in the different endoscopic resection (ER) techniques available, the major techniques being suck-and-cut ER and endoscopic submucosal dissection (ESD). Because of the risk of secondary neoplasia after curative endoscopic therapy, a standardized follow-up protocol is required. The majority of secondary neoplastic lesions can again be treated endoscopically. In the present article an overview of initial staging procedures, techniques, indications, as well as follow-up strategies after endoscopic therapy for early gastric cancer is given. PMID- 22090020 TI - [Minimally invasive gastric surgery]. AB - The interest in minimally invasive surgery (MIS) for the treatment of gastric carcinoma has increased in recent years worldwide. In particular, for early gastric carcinoma (EGC) many retrospective comparative trials and some prospective randomized trials have confirmed that laparoscopy-assisted distal gastrectomy shows a better short-term outcome in terms of lower morbidity, less pain, faster recovery and shorter hospital stay in contrast to open surgery. In this group of selected patients MIS is safe and feasible but at present not widely accepted because of a limited evaluation in oncologic long-term follow-up. In cases of EGC limited to the mucosal layer and under the condition that endoscopic resection is not suitable, laparoscopic local wedge resection or intragastric resection can be an alternative option with good results in long term follow-up. The data for laparoscopic total gastrectomy and MIS for advanced gastric cancer have confirmed that both are technically feasible and extended lymph node dissection can also be laparoscopically performed. However, laparoscopic total gastrectomy is much more complex and even in expert hands more complications and a higher morbidity have been observed in contrast to laparoscopic distal resections. PMID- 22090021 TI - Mechanistic investigations on dimethyl carbonate formation by oxidative carbonylation of methanol over a CuY zeolite: an operando SSITKA/DRIFTS/MS study. AB - The simultaneous combination of steady state isotopic transient kinetic analysis (SSITKA) with diffuse reflectance Fourier transform spectroscopy (DRIFTS) and mass spectrometric (MS) analysis was applied to study the oxidative carbonylation of methanol (MeOH) to dimethyl carbonate (DMC) on a CuY zeolite catalyst prepared by incipient-wetness impregnation of commercial zeolite NH(4)-Y. The interaction of the catalyst with different reactants and reactant mixtures (O(2), CO, CO/O(2), MeOH/O(2), MeOH/CO, and MeOH/CO/O(2)) was studied in detail using (16)O(2)/(18)O(2) as well as (12)CO/(13)CO containing gas mixtures. DMC is produced via a monodentate monomethyl carbonate (MMC) species as intermediate which is formed by the concerted action of adsorbed methoxide and CO with gas phase MeOH. Adsorbed bidentate MMC species were found to be inactive. Lattice oxygen supplied by CuO(x) species is involved in the formation of MMC. Gas phase oxygen is needed to re-oxidize the catalyst but favours also the oxidation of CO to CO(2) and unselective oxidation reactions of MeOH to methyl formate, dimethoxymethane, and CO(2). The appropriate choice of reaction temperature and of the oxygen content in the reactant gas mixture was found to be indispensable for reaching high DMC selectivities. PMID- 22090022 TI - Feasibility of surgery after systemic treatment with the humanized recombinant antibody bevacizumab in heavily pretreated patients with advanced epithelial ovarian cancer. AB - BACKGROUND: The aim of this study was to assess operative feasibility and outcome after bevacizumab treatment (BT) in ovarian cancer (OC) patients. PATIENTS AND METHODS: We retrospectively identified all OC patients operated between April 2006 and September 2010 after BT. RESULTS: We identified 733 OC operations, 10 of which (1.36%) were performed in a mean time of 134 days (range, 10-288) after BT. Indication was secondary cytoreduction in 3 patients (mean days after BT, 181; range, 82-256) and palliation in 7 due to bowel obstruction and/or intestinal perforation or fistula (mean days after BT, 114; range, 10-288). All but 1 acutely operated patients developed a secondary wound healing, but none of the 3 patients after planned cytoreduction did. Of these 3 patients, 1 suddenly died on the 36th postoperative day, presumably of thromboembolism. None of the patients developed postoperatively a gastrointestinal morbidity; however, in 1 patient operated 21 days after BT due to a vesicointestinal fistula the bladder reconstruction could not heal and developed a permanent fistula. CONCLUSIONS: Emergency surgery after BT due to bowel obstruction and/or fistulas seems to be associated with an impaired wound healing in advanced heavily pretreated platinum resistant OC patients, while this does not appear the case in planned cytoreduction. Prospective evaluations are warranted to assess surgical safety after BT in this special patients' collective. PMID- 22090023 TI - Establishment of Epstein-Barr virus growth-transformed lymphoblastoid cell lines. AB - Infection of B cells with Epstein-Barr virus (EBV) leads to proliferation and subsequent immortalization, resulting in establishment of lymphoblastoid cell lines (LCL) in vitro. Since LCL are latently infected with EBV, they provide a model system to investigate EBV latency and virus-driven B cell proliferation and tumorigenesis(1). LCL have been used to present antigens in a variety of immunologic assays(2, 3). In addition, LCL can be used to generate human monoclonal antibodies(4, 5) and provide a potentially unlimited source when access to primary biologic materials is limited(6, 7). A variety of methods have been described to generate LCL. Earlier methods have included the use of mitogens such as phytohemagglutinin, lipopolysaccharide(8), and pokeweed mitogen(9) to increase the efficiency of EBV-mediated immortalization. More recently, others have used immunosuppressive agents such as cyclosporin A to inhibit T cell mediated killing of infected B cells(7, 10-12). The considerable length of time from EBV infection to establishment of cell lines drives the requirement for quicker and more reliable methods for EBV-driven B cell growth transformation. Using a combination of high titer EBV and an immunosuppressive agent, we are able to consistently infect, transform, and generate LCL from B cells in peripheral blood. This method uses a small amount of peripheral blood mononuclear cells that are infected in vitroclusters of cells can be demonstrated. The presence of CD23 with EBV in the presence of FK506, a T cell immunosuppressant. Traditionally, outgrowth of proliferating B cells is monitored by visualization of microscopic clusters of cells about a week after infection with EBV. Clumps of LCL can be seen by the naked eye after several weeks. We describe an assay to determine early if EBV-mediated growth transformation is successful even before microscopic clusters of cells can be demonstrated. The presence of CD23(hi)CD58(+) cells observed as early as three days post-infection indicates a successful outcome. PMID- 22090024 TI - Pancreatic stem cells: from possible to probable. AB - Type 1 and some forms of type 2 diabetes mellitus are caused by deficiency of insulin-secretory islet beta cells. An ideal treatment for these diseases would therefore be to replace beta cells, either by transplanting donated islets or via endogenous regeneration (and controlling the autoimmunity in type 1 diabetes). Unfortunately, the poor availability of donor islets has severely restricted the broad clinical use of islet transplantation. The ability to differentiate embryonic stem cells into insulin-expressing cells initially showed great promise, but the generation of functional beta cells has proven extremely difficult and far slower than originally hoped. Pancreatic stem cells (PSC) or transdifferentiation of other cell types in the pancreas may hence provide an alternative renewable source of surrogate beta cells. However, the existence of PSC has been hotly debated for many years. In this review, we will discuss the latest development and future perspectives of PSC research, giving readers an overview of this controversial but important area. PMID- 22090025 TI - Compartmentation of triacylglycerol accumulation in plants. AB - Triacylglycerols from plants, familiar to most people as vegetable oils, supply 25% of dietary calories to the developed world and are increasingly a source for renewable biomaterials and fuels. Demand for vegetable oils will double by 2030, which can be met only by increased oil production. Triacylglycerol synthesis is accomplished through the coordinate action of multiple pathways in multiple subcellular compartments. Recent information has revealed an underappreciated complexity in pathways for synthesis and accumulation of this important energy rich class of molecules. PMID- 22090026 TI - Emerging role of lipid droplets in host/pathogen interactions. AB - Lipid droplets (LDs) are highly dynamic cell organelles involved in energy homeostasis and membrane trafficking. Here, we review how select pathogens interact with LDs. Several RNA viruses use host LDs at different steps of their life cycle. Some intracellular bacteria and parasites usurp host LDs or encode their own lipid biosynthesis machinery, thus allowing production of LDs independently of their host. Although many mechanistic details of host/pathogen LD interactions are unknown, a picture emerges in which the unique cellular architecture and energy stored in LDs are important in the replication of diverse pathogens. PMID- 22090027 TI - alpha-N-acetylgalactosaminidase from infant-associated bifidobacteria belonging to novel glycoside hydrolase family 129 is implicated in alternative mucin degradation pathway. AB - Bifidobacteria inhabit the lower intestine of mammals including humans where the mucin gel layer forms a space for commensal bacteria. We previously identified that infant-associated bifidobacteria possess an extracellular membrane-bound endo-alpha-N-acetylgalactosaminidase (EngBF) that may be involved in degradation and assimilation of mucin-type oligosaccharides. However, EngBF is highly specific for core-1-type O-glycan (Galbeta1-3GalNAcalpha1-Ser/Thr), also called T antigen, which is mainly attached onto gastroduodenal mucins. By contrast, core-3 type O-glycans (GlcNAcbeta1-3GalNAcalpha1-Ser/Thr) are predominantly found on the mucins in the intestines. Here, we identified a novel alpha-N acetylgalactosaminidase (NagBb) from Bifidobacterium bifidum JCM 1254 that hydrolyzes the Tn antigen (GalNAcalpha1-Ser/Thr). Sialyl and galactosyl core-3 (Galbeta1-3/4GlcNAcbeta1-3(Neu5Acalpha2-6)GalNAcalpha1-Ser/Thr), a major tetrasaccharide structure on MUC2 mucin primarily secreted from goblet cells in human sigmoid colon, can be serially hydrolyzed into Tn antigen by previously identified bifidobacterial extracellular glycosidases such as alpha-sialidase (SiaBb2), lacto-N-biosidase (LnbB), beta-galactosidase (BbgIII), and beta-N acetylhexosaminidases (BbhI and BbhII). Because NagBb is an intracellular enzyme without an N-terminal secretion signal sequence, it is likely involved in intracellular degradation and assimilation of Tn antigen-containing polypeptides, which might be incorporated through unknown transporters. Thus, bifidobacteria possess two distinct pathways for assimilation of O-glycans on gastroduodenal and intestinal mucins. NagBb homologs are conserved in infant-associated bifidobacteria, suggesting a significant role for their adaptation within the infant gut, and they were found to form a new glycoside hydrolase family 129. PMID- 22090028 TI - Photosystem II component lifetimes in the cyanobacterium Synechocystis sp. strain PCC 6803: small Cab-like proteins stabilize biosynthesis intermediates and affect early steps in chlorophyll synthesis. AB - To gain insight in the lifetimes of photosystem II (PSII) chlorophyll and proteins, a combined stable isotope labeling (15N)/mass spectrometry method was used to follow both old and new pigments and proteins. Photosystem I-less Synechocystis cells were grown to exponential or post-exponential phase and then diluted in BG-11 medium with [15N]ammonium and [15N]nitrate. PSII was isolated, and the masses of PSII protein fragments and chlorophyll were determined. Lifetimes of PSII components ranged from 1.5 to 40 h, implying that at least some of the proteins and chlorophyll turned over independently from each other. Also, a significant amount of nascent PSII components accumulated in thylakoids when cells were in post-exponential growth phase. In a mutant lacking small Cab-like proteins (SCPs), most PSII protein lifetimes were unaffected, but the lifetime of chlorophyll and the amount of nascent PSII components that accumulated were decreased. In the absence of SCPs, one of the PSII biosynthesis intermediates, the monomeric PSII complex without CP43, was missing. Therefore, SCPs may stabilize nascent PSII protein complexes. Moreover, upon SCP deletion, the rate of chlorophyll synthesis and the accumulation of early tetrapyrrole precursors were drastically reduced. When [14N]aminolevulinic acid (ALA) was supplemented to 15N-BG-11 cultures, the mutant lacking SCPs incorporated much more exogenous ALA into chlorophyll than the control demonstrating that ALA biosynthesis was impaired in the absence of SCPs. This illustrates the major effects that nonstoichiometric PSII components such as SCPs have on intermediates and assembly but not on the lifetime of PSII proteins. PMID- 22090029 TI - Packaging of fat: an evolving model of lipid droplet assembly and expansion. AB - Lipid droplets (LDs) are organelles found in most types of cells in the tissues of vertebrates, invertebrates, and plants, as well as in bacteria and yeast. They differ from other organelles in binding a unique complement of proteins and lacking an aqueous core but share aspects of protein trafficking with secretory membrane compartments. In this minireview, we focus on recent evidence supporting an endoplasmic reticulum origin for LD formation and discuss recent findings regarding LD maturation and fusion. PMID- 22090030 TI - Molecular mechanism for inhibition of a critical component in the Arabidopsis thaliana abscisic acid signal transduction pathways, SnRK2.6, by protein phosphatase ABI1. AB - Subclass III SnRK2s (SnRK2.6/2.3/2.2) are the key positive regulators of abscisic acid (ABA) signal transduction in Arabidopsis thaliana. The kinases, activated by ABA or osmotic stress, phosphorylate stress-related transcription factors and ion channels, which ultimately leads to the protection of plants from dehydration or high salinity. In the absence of stressors, SnRK2s are subject to negative regulation by group A protein phosphatase type 2Cs (PP2C), whereas the underlying molecular mechanism remains to be elucidated. Here we report the crystal structure of the kinase domain of SnRK2.6 at 2.6-A resolution. Structure-guided biochemical analyses identified two distinct interfaces between SnRK2.6 and ABI1, a member of group A PP2Cs. Structural modeling suggested that the two interfaces lock SnRK2.6 and ABI1 in an orientation such that the activation loop of SnRK2.6 is posited to the catalytic site of ABI1 for dephosphorylation. These studies revealed the molecular basis for PP2Cs-mediated inhibition of SnRK2s and provided important insights into the downstream signal transduction of ABA. PMID- 22090031 TI - Human protein-disulfide isomerase is a redox-regulated chaperone activated by oxidation of domain a'. AB - Protein-disulfide isomerase (PDI), with domains arranged as abb'xa'c, is a key enzyme and chaperone localized in the endoplasmic reticulum (ER) catalyzing oxidative folding and preventing misfolding/aggregation of proteins. It has been controversial whether the chaperone activity of PDI is redox-regulated, and the molecular basis is unclear. Here, we show that both the chaperone activity and the overall conformation of human PDI are redox-regulated. We further demonstrate that the conformational changes are triggered by the active site of domain a', and the minimum redox-regulated cassette is located in b'xa'. The structure of the reduced bb'xa' reveals for the first time that domain a' packs tightly with both domain b' and linker x to form one compact structural module. Oxidation of domain a' releases the compact conformation and exposes the shielded hydrophobic areas to facilitate its high chaperone activity. Thus, the study unequivocally provides mechanistic insights into the redox-regulated chaperone activity of human PDI. PMID- 22090032 TI - Thematic minireview series on the lipid droplet, a dynamic organelle of biomedical and commercial importance. PMID- 22090033 TI - Structural and mechanistic implications of metal binding in the small heat-shock protein alphaB-crystallin. AB - The human small heat-shock protein alphaB-crystallin (alphaB) rescues misfolded proteins from irreversible aggregation during cellular stress. Binding of Cu(II) was shown to modulate the oligomeric architecture and the chaperone activity of alphaB. However, the mechanistic basis of this stimulation is so far not understood. We provide here first structural insights into this Cu(II)-mediated modulation of chaperone function using NMR spectroscopy and other biophysical approaches. We show that the alpha-crystallin domain is the elementary Cu(II) binding unit specifically coordinating one Cu(II) ion with picomolar binding affinity. Putative Cu(II) ligands are His(83), His(104), His(111), and Asp(109) at the dimer interface. These loop residues are conserved among different metazoans, but also for human alphaA-crystallin, HSP20, and HSP27. The involvement of Asp(109) has direct implications for dimer stability, because this residue forms a salt bridge with the disease-related Arg(120) of the neighboring monomer. Furthermore, we observe structural reorganization of strands beta2-beta3 triggered by Cu(II) binding. This N-terminal region is known to mediate both the intermolecular arrangement in alphaB oligomers and the binding of client proteins. In the presence of Cu(II), the size and the heterogeneity of alphaB multimers are increased. At the same time, Cu(II) increases the chaperone activity of alphaB toward the lens-specific protein beta(L)-crystallin. We therefore suggest that Cu(II) binding unblocks potential client binding sites and alters quaternary dynamics of both the dimeric building block as well as the higher order assemblies of alphaB. PMID- 22090037 TI - Automated detection of dark and bright lesions in retinal images for early detection of diabetic retinopathy. AB - There is an ever-increasing interest in the development of automatic medical diagnosis systems due to the advancement in computing technology and also to improve the service by medical community. The knowledge about health and disease is required for reliable and accurate medical diagnosis. Diabetic Retinopathy (DR) is one of the most common causes of blindness and it can be prevented if detected and treated early. DR has different signs and the most distinctive are microaneurysm and haemorrhage which are dark lesions and hard exudates and cotton wool spots which are bright lesions. Location and structure of blood vessels and optic disk play important role in accurate detection and classification of dark and bright lesions for early detection of DR. In this article, we propose a computer aided system for the early detection of DR. The article presents algorithms for retinal image preprocessing, blood vessel enhancement and segmentation and optic disk localization and detection which eventually lead to detection of different DR lesions using proposed hybrid fuzzy classifier. The developed methods are tested on four different publicly available databases. The presented methods are compared with recently published methods and the results show that presented methods outperform all others. PMID- 22090040 TI - Tuberculosis through the rose tinted spectacles of the EBUS endoscopist: be aware of the bias. PMID- 22090041 TI - Developments in in vivo monitoring for radionuclides at AWE. AB - The Atomic Weapons Establishment (AWE) has routinely used high purity germanium crystals for in vivo monitoring, detection and measurement of radionuclides in the chest, wounds and whole body of personnel over the past 30 years. However, recent organisational changes have resulted in the relocation and modification of this capability. Hence, this paper reviews and compares the performance of the original twin six crystal detector arrays (contained within environmental radiation shielding), that were first used at AWE in 1980, with the latest unshielded systems that employ smaller numbers of larger crystals. It has been concluded that the required sensitivity of 20 mSv for actinides in the chest was achieved using the recently procured twin dual crystal detector arrays outside of the conventional heavy duty environmental radiation shield used with the original system. Sensitivities of around 1 uSv, for fission and activation products in the whole body and around 1 mSv, for actinides in wounds, were achieved using single large collimated, but otherwise unshielded, detectors. PMID- 22090038 TI - Association between obstructive lung disease and markers of HIV infection in a high-risk cohort. AB - BACKGROUND: Evidence suggests an association between HIV infection and the presence of obstructive lung disease (OLD). However, the associations between specific markers of HIV infection and OLD remain unclear. A study was undertaken to determine the independent associations of HIV infection, CD4 cell count and plasma HIV viral load with the presence of OLD in an urban cohort. METHODS: Clinical, laboratory and spirometric data from the AIDS Linked to the Intravenous Experience (ALIVE) study, an observational study of current and former injection drug users in Baltimore, Maryland, were analysed. Multivariable logistic regression models were generated to identify HIV infection indices independently associated with OLD. RESULTS: Of 1077 participants (mean+/-SD age 48+/-8 years), 89% were African-American, 65% were men and 86% were current smokers. A total of 303 (28%) were HIV infected and 176 (16%) had spirometry-defined OLD. Higher viral load was independently associated with OLD. HIV-infected individuals with viral load >200,000 copies/ml had a 3.4-fold increase in the odds of OLD compared with HIV-negative participants (95% CI 1.24 to 9.39; p=0.02). The association between higher HIV viral load and OLD persisted after accounting for antiretroviral therapy use (OR 4.06, 95% CI 1.41 to 11.7; p=0.01). No association was observed between HIV serostatus or CD4 cell count and the presence of OLD. CONCLUSION: In a cohort at risk for OLD and HIV infection, high viral load but not CD4 cell count was associated with an increased prevalence of spirometry defined OLD. These findings suggest that higher viral load may contribute mechanistically to the increased risk of OLD in patients with HIV infection. PMID- 22090042 TI - Supine percutaneous nephrolithotomy: pro. AB - PURPOSE: To share the experience of the authors with the urological family in the world by the review of literature on supine percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: We have searched all the available databases, including PubMed or MEDLINE and Embase Biomedical Database to find any English articles related to supine PCNL from 1998 to 2010. Of 17 studies, 11 were case series and 6 were comparative. RESULTS: A total of 1914 patients were studied. Only the results of mean operation time were significant. Supine PCNL offers several advantages, including less operation time, less patient handling, needing only one drape, easier access to the urethra and upper calyces, facilitation of drainage of stone fragment with the Amplatz sheath, less anterior kidney displacement due to lying the kidney in its normal anatomical position, less risk of the colon injury, more tolerable for the patients with pulmonary or cardiovascular disease, and better for morbid obese patients. The overlap density of the vertebrae in the semi-supine position can be avoided. Furthermore, the fluoroscopy tube is far from the puncture site; thus, the space is open for the surgeon to work and the surgeon can perform the procedure in a more comfortable seated position. CONCLUSION: The study showed that PCNL in the supine position is feasible. Although supine PCNL has numerous advantages, it is not routine in many surgical centers throughout the world. The practice of supine PCNL will be popular when the academic centers be encouraged to start it. PMID- 22090043 TI - Supine percutaneous nephrolithotomy: con. AB - Advocates of supine percutaneous nephrolithotomy (PCNL) consider several theoretical advantages for this procedure. Despite the potential advantages of the supine PCNL, the majority of urologists have remained reluctant to perform this technique. This reluctance may be related to successful outcomes of prone PCNL and technical difficulties associated with supine PCNL. Feasibility of supine PCNL has been shown in different series and the current evidence, although limited and not fully organized, implies the application of this technique for patients with simple stones who are at high anesthesiological risk. However, there is no convincing evidence to support performing supine PCNL in morbidly obese patients and those with complex and multiple stones. Further randomized clinical trials of large sample size and high methodological quality are required to recommend extensive application of supine PCNL as an alternative to prone PCNL. PMID- 22090044 TI - Percutaneous nephrolithotomy complications in 671 consecutive patients: a single center experience. AB - PURPOSE: To evaluate major and minor complications of percutaneous nephrolithotomy (PCNL) and their management in our consecutive cases. MATERIALS AND METHODS: We reviewed medical records of 671 patients who had undergone PCNL in our center from March 2000 to March 2006. The demographic data, stone parameters, PCNL complications, and stone-free rate were evaluated. Multiple parameters were evaluated for their association with PCNL complications using Chi Square test. RESULTS: Complications occurred in 203 (30.3%) patients; renal parenchymal injury in 103 (15.4%), peri-operative bleeding in 42 (6.3%), late bleeding in 6 (0.9%), renal collecting ducts injury in 35 (5.2%), fever in 7 (1.0%), colon perforation in 2 (0.3%), major vessels injury in 3 (0.4%), pneumothorax in 3 (0.4%), and hemothorax in 2 (0.3%) subjects. Mortality occurred in 1 patient with colon perforation (0.15%). CONCLUSION: Percutaneous nephrolithotomy has low complication rate in experienced hands. PMID- 22090045 TI - Evaluating percutaneous nephrolithotomy-induced kidney damage by measuring urinary concentrations of beta2-microglobulin. AB - PURPOSE: To assess percutaneous nephrolithotomy (PCNL)-induced kidney tubular damage and the associated factors. MATERIALS AND METHODS: One hundred and eight patients who have undergone PCNL from May 2007 to October 2007 were recruited in this study. Urinary level of beta2-microglobulin (Ubeta2MG) was measured on the day before the operation as well as on the 1st and 7th post PCNL days. Percutaneous nephrolithotomy was performed using standard method. Patients' demographic and peri-operative data were collected to evaluate factors influencing renal injury. RESULTS: Median urinary levels of beta2-microglobulin on pre-operative, 1st, and 7th postoperative days were 0.2 mg/dL (range, 0.1 to 82), 0.4 mg/dL (range, 0.2 to 97), and 0.2 mg/dL (range, 0.2 to 114), respectively. High levels of Ubeta2MG (> 2.3 mg/dL) were observed in 10 (9%), 20 (19%), and 10 (9%) patients pre-operatively and on the 1st, and 7th postoperative days, respectively. In multivariable analysis, Ubeta2MG on the 1st postoperative day was associated with pre-operative serum creatinine level (P < .001) and diabetes mellitus (P = .05), while Ubeta2MG on the 7th day after the operation was associated with pre-operative serum creatinine level (P = .01), diabetes mellitus (P = .01), and PCNL time (P = .02). CONCLUSION: Percutaneous nephrolithotomy does not cause kidney tubular injury beyond one week. In patients with pre-operative high serum creatinine concentration, diabetes mellitus, and/or long operation time, the likelihood of the kidney damage is higher than others. PMID- 22090046 TI - "Latex glove" laparoscopic pyeloplasty model: a novel method for simulated training. AB - PURPOSE: To present a 'latex glove' laparoscopic pyeloplasty (LPP) training model and determine its construct validity for its effective use in resident training. MATERIALS AND METHODS: The 'latex glove' model was used to perform LPP by five operators with variable level of experience, ranging from an experienced (> 20 independent LPPs) to minimal operative experience (year 5 medical student). The palm of the glove was considered the renal pelvis with finger of the glove as the proximal ureter. A knot at the junction of the two was considered as ureteropelvic junction obstruction. A basic lap trainer was used to simulate the LPP. Operation time was noted in minutes and quality of continuous suturing was determined for each operator, using a previously described nonvalidated scoring system by a blinded reviewer. RESULTS: The operation time varied from 47 to 160 minutes for the most to the least experienced operator, and the difference was statistically significant (P = .043), while the quality of suturing score ranged from 1 to 6 for the most to the least experienced operator, respectively (P = .038). The operation time and quality of suturing were negatively correlated with the level of experience (-0.962 and -0.987, respectively), which were statistically significant (P = .009 and P = .002, respectively). CONCLUSION: This novel training model has proven its validity, as a cost-effective and readily available option for LPP training. PMID- 22090047 TI - Management and follow-up of pediatric asymptomatic testicular microlithiasis: are we doing it well? AB - PURPOSE: To define timing and methods for a balanced follow-up of testicular microlithiasis (TM) in pediatric age. MATERIALS AND METHODS: We retrospectively reviewed medical records of 21 pediatric asymptomatic patients (42 testicular units) diagnosed with TM and without associated risk factors. Microliths were found bilaterally on ultrasonography in all the patients. Distribution of microliths (focal or diffuse) inside the parenchyma was evaluated as well as its eventual variation over time. Every six months, each patient underwent clinical and ultrasonography evaluation, as well as serum chemistry markers (alpha fetoprotein and beta-human chorionic gonadotropin) measurement to detect potential malignancy. In the interval between the follow-ups, parents and/or patients themselves were asked to control eventual enlargement of the gonads or scrotal swelling. Testicular biopsy was not performed in any of our subjects. RESULTS: Of 21 patients, 6 had unilateral undescended testis, 4 varicocele, and 1 patent processus vaginalis with scrotal swelling while 10 patients did not show associated anomalies. The distribution pattern of microliths on ultrasonography remained unchanged in all follow-ups in every patient, showing a predominance of diffuse pattern in the undescended testis series. Tumor markers remained within normal limits. In no subject, we observed a shift toward a malignant condition. CONCLUSION: In the pediatric population with an incidentally diagnosed TM and without any associated risk factor, a slight follow-up is suggested, consisting of clinical evaluation every 6 months, without any justifiable recommendation to perform a testis biopsy and a measurement of serum tumor markers. PMID- 22090048 TI - Risk factors for disconcordance between pre and post radical cystectomy stages. AB - PURPOSE: To investigate the correlation between pre and post surgical staging in patients undergoing radical cystectomy (RC), and study the possibility of predicting their disconcordance. MATERIALS AND METHODS: We reviewed medical records of 186 patients diagnosed with transitional cell carcinoma of the bladder, who had undergone RC between the years 2007 and 2010. We determined the correlation between pre and post surgical stages and then studied the association between stage disconcordance and age, gender, smoking, history of previous transurethral resection of bladder tumor (TURBT) and intravesical treatments, re TURBT in high-risk superficial bladder tumors, and the treatment delay between diagnosis and RC. Analysis was performed using Chi-Square and Fisher's Exact tests. RESULTS: Post surgical up-staging occurred in 86 (46.24%) patients and even more (69.35%) if lymph node involvement was also considered as up-staging. Smokers and those with pre surgical stages of <= T1 and T2 with no history of re TURBT had a significantly increased risk of disconcordance. The risk of up staging was almost halved by an early re-TURBT in high-risk patients. CONCLUSION: Disconcordance between pre and post surgical stages in patients undergoing RC is common. Until better ways of staging are developed, decision making in patients with bladder tumor should be done by extra attention to patients who have risk factors associated with increased risk of up-staging, including smokers and those with nonmuscle-invasive bladder tumors or T2 tumors. An early re-TURBT will decrease the up-staging rate. PMID- 22090049 TI - Is microsurgery necessary in grade 3 varicocele? AB - PURPOSE: To compare the results of microsurgical and naked eye varicocelectomy in patients with grade 3 varicocele. MATERIALS AND METHODS: This study was conducted on 84 patients with grade 3 varicocele, between 2007 and 2009. Patients were randomized into two groups, equal in number. Thereafter, microsurgical varicocelectomy was performed in the first group, while the other group underwent naked eye varicocelectomy. Groups were compared in terms of operation duration, number of ligated internal and external spermatic veins, early and late postoperative complications, and postoperative color Doppler ultrasonography findings. Parametric and nonparametric values were compared using Student's t test and Chi-Square test, respectively. RESULTS: The mean duration of surgery was 19 +/- 2.3 minutes (range, 12 to 25 minutes) in the naked eye surgery group and 43 +/- 3.9 minutes (range, 25 to 75 minutes) in the microsurgery group (P = .008). The number of ligated internal and external spermatic veins, the incidence of early and late postoperative complications, and color Doppler ultrasonography findings were not significantly different between the two groups (P = .12, P = .09, P = .17, and P = .22, respectively). CONCLUSION: In patients with grade 3 varicocele, microsurgery and naked eye surgical methods proved similar results in terms of success and complications. Because the operation time of the classical varicocelectomy is significantly shorter, it may be preferred in this subset of patients. PMID- 22090050 TI - Comparing absorbable and nonabsorbable sutures in corporeal plication for treatment of congenital penile curvature. AB - PURPOSE: To compare the outcome of corporeal plication using absorbable versus nonabsorbable sutures for the treatment of congenital penile curvature. MATERIALS AND METHODS: Thirty-eight men older than 15 years old with congenital penile curvature were enrolled in the study. Patients were randomly divided into two equal groups based on the suture material (Nylon versus Vicryl) used in corporeal plication. Patients were followed up for a mean period of 8.1 +/- 1.4 months (range, 6 to 9.1 months). A standardized questionnaire was used to evaluate long term outcome and patient's satisfaction. RESULTS: Thirty-five patients (17 in Vicryl group and 18 in Nylon group) completed the study. Mean age of the patients and degree of penile curvature were not significantly different between the two groups (P = .74). Postoperatively, 15 (88.2%) and 16 (88.9%) patients in Vicryl and Nylon groups had 75% or greater correction in penile curvature, respectively (P = .61). Patient's satisfaction rate differed between two groups (82% in Vicryl group versus 66% in Nylon group), which did not reach statistical significance (P = .44). Palpable sutures were reported by 7 (39%) patients in Nylon group and only 1 (6%) in Vicryl group (P = .04). Shortening of penile length was reported by 3 (16.7%) patients in Nylon group and 4 (23.5%) in Vicryl group (P = .69). CONCLUSION: Corporeal plication technique using absorbable suture provides reasonable success rate with less frequent palpable suture knots. PMID- 22090051 TI - One-stage transperineal repair of pan-urethral stricture with dorsally placed buccal mucosal grafts: results, complications, and surgical technique. AB - PURPOSE: To report the surgical details and results of one-stage transperineal urethroplasty using dorsal buccal mucosal graft (BMG) in treatment of panurethral stricture. MATERIALS AND METHODS: This cohort study was carried out on 17 men with pan-urethral stricture who underwent one-stage transperineal BMG urethroplasty. Failure was defined as a need to any intervention during the follow-up period. RESULTS: The etiology of stricture was trauma in 4 (23.5%), sexually transmitted diseases in 4 (23.5%), lichen sclerosus in 2 (11.8%), and idiopathic in 7 (41.1%) patients. The mean follow-up period was 8.5 months (range, 3 to 18 months). Six (35.3%) patients developed complications; namely wound infection in 2 (11.8%), meatal stenosis in 1 (5.9%), and re-stenosis in 3 (17.6%) subjects. Complication rate in patients <= 43 and > 43 years old was 25% (2/8) and 44% (4/9), respectively, which did not reach statistically significant difference (P = .6). The final success rate was 88.2%. None of the patients needed open redo-urethroplasty during the follow-up period. CONCLUSION: Reconstruction of pan-urethral strictures may be safely and effectively performed at a simple single operative procedure using a transperineal approach with combinations of dorsal BMG. PMID- 22090052 TI - Protective effects of zofenopril on testicular torsion and detorsion injury in rats. AB - PURPOSE: To investigate the protective effect of zofenopril on torsion/detorsion induced biochemical and histopathological changes in experimental testicular ischemia or reperfusion injury in rats. MATERIALS AND METHODS: A total of 35 prepubertal male Wistar-Albino rats were divided into five groups, including 7 rats in each group: Group I (sham, S), sham operation; group II (torsion/detorsion-early orchiectomy, T/D-E), 2 hours ischemia and 4 hours reperfusion; group III (torsion/detorsion-late orchiectomy), T/D-L), 2 hours ischemia and 5 days reperfusion; group IV (zofenopril-early orchiectomy, Z-E), 2 hours ischemia, 4 hours reperfusion, and a single dose of zofenopril; and group V (zofenopril-late orchiectomy, Z-L), 2 hours ischemia, 5 days reperfusion, and 5 doses of zofenopril. We determined the tissue levels of malondialdehyde, nitric oxide, glutathione peroxidase, and superoxide dismutase enzyme activities. Histopathologically, mean seminiferous tubule diameter measurements were used. RESULTS: Malondialdehyde (3.490 +/- 0.89 versus 1.729 +/- 0.25 in early period; 3.837 +/- 1.694 versus 1.694 +/- 0.47 in late period) and nitric oxide levels (3.507 +/- 0.44 versus 2.853 +/- 0.54 in early period; 4.010 +/- 0.72 versus 2.446 +/- 0.29 in late period) significantly reduced and glutathione peroxidase (0.012 +/- 0.001 versus 0.017 +/- 0.001 in early period; 0.013 +/- 0.002 versus 0.018 +/- 0.001 in late period) and superoxide dismutase enzyme activities (58.030 +/- 5.97 versus 70.773 +/- 3.85 in early period; 57.421 +/- 7.81 versus 76.329 +/- 4.09 in late period) significantly increased in the testis tissue in zofenopril pretreated groups compared to group T/D both in early and late period (P < .05). The mean seminiferous tubule diameter was significantly better in pretreated group (210.33 +/- 17.32) than group T/D (185.02 +/- 22.45) only in late period (P < .05), but not in early period (209.38 +/- 30.40 versus 208.21 +/ 13.57; P > .05). CONCLUSION: Treatment with zofenopril decreased damage in ipsilateral testis caused by ischemia/reperfusion, and clinical application of zofenopril might be a new approach for the treatment of testicular torsion in addition to conventional detorsion. PMID- 22090053 TI - Assessment of increased desquamation of epididymal epithelial cells in semen of men as a predictor of acute epididymitis. PMID- 22090054 TI - An unusual presentation of an uncommon renal disease. PMID- 22090055 TI - Is extracorporeal shockwave lithotripsy safe in patients with chronic bleeding tendency? PMID- 22090056 TI - Concealed male epispadias: a rare form of penile epispadias presenting as phimosis. PMID- 22090057 TI - Prostatic cyst causing severe infravesical obstruction in a young patient. PMID- 22090058 TI - Hydronephrosis secondary to sliding inguinal hernia containing the ureter. PMID- 22090059 TI - Myiasis with carcinoma in situ of the glans penis: an unusual combination. PMID- 22090060 TI - Renal osteodystrophy secondary to congenital bilateral ureteropelvic junction obstruction. PMID- 22090061 TI - Dietary CLA combined with palm oil or ovine fat differentially influences fatty acid deposition in tissues of obese Zucker rats. AB - The effect of dietary conjugated linoleic acid (CLA) supplementation in combination with fat from vegetable versus animal origin on the fatty acid deposition, including that of individual 18:1 and 18:2 (conjugated and non conjugated) isomers, in the liver and muscle of obese rats was investigated. For this purpose, 32 male Zucker rats were randomly assigned to one of four diets containing palm oil or ovine fat, supplemented or not with 1% of 1:1 cis(c)9,trans(t)11 and t10,c12 CLA isomers mixture. Total fatty acid content decreased in the liver and muscle of CLA-fed rats. In the liver, CLA increased saturated fatty acids (SFA) in 11.9% and decreased monounsaturated fatty acids (MUFA) in 6.5%. n-3 Polyunsaturated fatty acids (PUFA) relative proportions were increased in 30.6% by CLA when supplemented to the ovine fat diet. In the muscle, CLA did not affect SFA but decreased MUFA and PUFA percentages. The estimation of Delta9-indices 16 and 18 suggested that CLA inhibited the stearoyl-CoA desaturase activity in the liver (a decrease of 13-38%), in particular when supplemented to the ovine fat diet. Concerning CLA supplementation, the t10,c12 isomer percentage was 60-80% higher in the muscle than in the liver. It is of relevance that rats fed ovine fat, containing bio-formed CLA, had more c9,t11 CLA isomer deposited in both tissues than rats fed palm oil plus synthetic CLA. These results highlight the importance to further clarify the biological effects of consuming foods naturally enriched in CLA, alternatively to CLA dietary supplementation. PMID- 22090062 TI - Low levels of lipogenic enzymes in peritumoral adipose tissue of colorectal cancer patients. AB - Lipoprotein lipase (LPL) is the crucial enzyme for intravascular catabolism of triglyceride-rich lipoproteins. Fatty acid synthase (FAS) is a key anabolic enzyme that catalyzes the terminal steps in the novo biosynthesis of 18:2n-6. The involvement of both LPL and FAS in tumor biology has been widely demonstrated in different studies and to verify whether there are regional differences in the expression of these enzymes in visceral adipose tissue from patients with colorectal cancer might be representative of events which sustain tumor growth. The objective of this study was to evaluate LPL and FAS activity and expression of their genes in adipose tissue adjacent to neoplasia and distant from it from patients operated for colorectal cancer. LPL enzymatic activity was evaluated by a fluorescent method and FAS activity by a radiometer assay. Reverse transcription and real-time PCR were used to detect mRNA levels of two enzymes. Our findings show a significant reduction in both LPL and FAS gene expression and activity levels in adipose tissue adjacent to tumor lesion compared to those detected in paired tissue distant from neoplasia. These results underline the influence of tumor microenvironment on lipid metabolism in adipose tissue, demonstrating a tumor-induced impairment in the formation and lipid storing capacity of adipose tissue in patients with colorectal cancer. PMID- 22090064 TI - Cardiovascular determinants of exercise capacity in the Paralympic athlete with spinal cord injury. AB - This report briefly summarizes the cardiovascular factors that influence exercise physiology and, eventually, sports performance of athletes with a spinal cord injury (SCI). The consequences of an SCI are numerous and concern voluntary muscle function, deep and superficial sensitivity, and autonomic function to a degree determined by the level and completeness of the spinal lesion. Athletes with SCI perform with their upper body, which limits their maximal exercise capacity and puts them at a disadvantage compared with leg exercise in terms of mechanical efficiency and physiological adaptations to exercise. Studies generally find that maximal oxygen consumption and mechanical power output are inversely related to spinal lesion level. Athletes with cervical or dorsal lesions down to Th6 have limited maximal heart rates owing to a lack of sympathetic drive to the heart. Blood redistribution from body areas lacking autonomic control is impaired, thus reducing venous return and limiting cardiac stroke volume during exercise. Thermoregulatory function is affected through a lack of afferent neural feedback and limited efferent vasomotor and sudomotor control below the lesion. Strategies to support venous return and to promote body cooling potentially improve physiological responses and athletic performance, especially in individuals with high lesion levels. The latter are subject to autonomic dysreflexia, a generalized sympathetic vasoconstriction below the lesion resulting from nociceptive stimulations in insensate body regions. Acute episodes induce high blood pressure, may enhance exercise performance and must be treated as a clinical emergency. Deliberate triggering of this reflex is prohibited by the International Paralympic Committee. PMID- 22090063 TI - Orthostatic leg blood volume changes assessed by near-infrared spectroscopy. AB - Standing up shifts blood to dependent parts of the body, and blood vessels in the leg become filled. The orthostatic blood volume accumulation in the small vessels is relatively unknown, although these may contribute significantly. We hypothesized that in healthy humans exposed to the upright posture, volume accumulation in small blood vessels contributes significantly to the total fluid volume accumulated in the legs. Considering that near-infrared spectroscopy (NIRS) tracks postural blood volume changes within the small blood vessels of the lower leg, we evaluated the NIRS-determined changes in oxygenated (Delta[O(2)Hb]), deoxygenated (Delta[HHb]) and total haemoglobin tissue concentration (Delta[tHb]) and in total leg volume by strain-gauge plethysmography during 70 deg head-up tilt (HUT; n = 7). In a second experiment, spatial and temporal reproducibility were evaluated with three NIRS probes applied on two separate days (n = 8). In response to HUT, an initially fast increase in [O(2)Hb] was followed by a gradual decline, while [HHb] increased continuously. The increase in [tHb] during HUT was closely related to the increase in total leg volume (r(2) = 0.95 +/- 0.03). After tilt back, [O(2)Hb] declined below and [HHb] remained above baseline, whereas all NIRS signals gradually returned to baseline. Spatial heterogeneity was observed, and for two probes [tHb] was highly correlated between days (r(2) = 0.92 +/- 0.09 and 0.91 +/ 0.12), but less for the third probe (r(2) = 0.44 +/- 0.36). The results suggest a non-linear accumulation of blood volume in the small vessels of the leg, with an initial fast phase followed by a more gradual increase at least partly contributing to the relocation of fluid during orthostatic stress. PMID- 22090065 TI - Breathing 40% O(2) can attenuate postcontraction hyperaemia or muscle fatigue caused by static forearm contraction, depending on timing. AB - Little is known of the role of O(2)-dependent mechanisms in the hyperaemia associated with static muscle contraction or recovery from fatigue. Thus, in recreationally active, young, male subjects, forearm contraction was performed twice at 100% maximal voluntary effort until exhaustion, with a 7 min recovery period, whilst 40% O(2) (hyperoxia) was breathed during the contractions only, or during recovery only, or room air (normoxia) was breathed throughout. When hyperoxia was limited to the contractions, postcontraction increases in forearm blood flow, measured by venous occlusion plethysmography, were ~25% lower (P < 0.05, n = 10) than during normoxia throughout. Furthermore, the postcontraction increase in venous lactate and fall in pH were attenuated (P < 0.05, n = 8). However, there was no effect on fatigue; time to voluntary exhaustion of contraction 2 was ~25% less than for contraction 1 in both conditions. By contrast, when hyperoxia was limited to recovery (n = 10), there was no effect on postcontraction increases in forearm blood flow, but fatigue was ameliorated; time to voluntary exhaustion of contraction 2 was comparable to that of contraction 1. These results allow the novel conclusions that, even during static forearm contraction at 100% maximal voluntary effort, additional O(2) dissolved in plasma can attenuate the contribution made by O(2) dependent dilator substances to postcontraction hyperaemia and that these substances may be released from the muscle fibres or blood vessel wall. Furthermore, they indicate that even in recreationally active individuals, recovery from fatigue can be improved by additional O(2) made available during recovery, and the O(2)-dependent mechanisms that contribute to fatigue are different from those that induce postcontraction hyperaemia. PMID- 22090066 TI - Epithelial Na+ channel proteins are mechanotransducers of myogenic constriction in rat posterior cerebral arteries. AB - It has been suggested that mechanosensitive ion channels initiate myogenic responses in vessels; however, the molecular identity of the mechanosensitive ion channel complex is unknown. Although previous reports have suggested that epithelial Na(+) channel (ENaC) proteins are mechanotransducers in arteries, experimental evidence demonstrating that ENaC proteins are mechanotransducers are not fully elucidated. The goal of the present study was to determine whether the ENaC is a mechanotransducer for the myogenic response by providing supporting evidence in the rat posterior cerebral artery (PCA). We measured the effect of ENaC inhibition on the pressure-induced myogenic response, Ca(2+) concentration and 20 kDa myosin light chain (MLC(20)) phosphorylation. We detected expression of betaENaC and gammaENaC subunits in rat PCA by Western blots and immunofluorescence. Inhibition of ENaCs with amiloride, ethyl isopropyl amiloride or benzamil blocked the myogenic response. Moreover, the myogenic response was inhibited in rat PCA transfected with betaENaC and gammaENaC small interfering RNA. The myogenic response was inhibited by elimination of external Na(+), which was replaced with N-methyl-d-glucamine. Amiloride and nifedipine inhibited the pressure-induced increase in Ca(2+) concentration. Finally, MLC(20) increased when the intraluminal pressure was raised, and the pressure-induced increase in MLC(20) phosphorylation was inhibited by pretreatment with amiloride, and in arteries transfected with betaENaC or gammaENaC small interfering RNA. Our results suggest that ENaCs may play an important role as mechanosensitive ion channels initiating pressure-induced myogenic responses in rat PCA. PMID- 22090067 TI - Translating research to practice. PMID- 22090068 TI - Validation of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). AB - PURPOSE: Preliminary validation of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) for motor skill assessment in spinal muscular atrophy type I. METHODS: A total of 27 subjects 3 to 260 months old (mean = 49, SD = 69) with spinal muscular atrophy-I were evaluated with the CHOP INTEND. Subjects were evaluated as part of a multicenter natural history study. RESULTS: CHOP INTEND scores and age were significantly correlated (r = 0.51, P = .007; 2 survival of the motor neuron [SMN] 2 gene copies, n = 16, r = 0.60, 3 SMN2 gene copies, n = 9, r = -0.83). Respiratory support and CHOP INTEND scores were correlated (r = -0.74, P < .0001, n = 26). The CHOP INTEND and age regression in patients with 2 copies versus 3 copies of SMN2 approached significance (P = .0711, n = 25). Subjects who required respiratory support scored significantly lower (mean = 15.5, SD = 10.2 vs mean = 31.2, SD = 4.2, P < .0001, n = 27). Correlation with motor unit number estimation and combined motor unit activation were not significant. CONCLUSION: The CHOP INTEND reflects measures of disease severity and supports continued exploration of the CHOP INTEND. PMID- 22090069 TI - Commentary on "Validation of the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND)". PMID- 22090070 TI - Expiratory flow increase technique and acid esophageal exposure in infants born preterm with bronchopulmonary dysplasia. AB - OBJECTIVE: To determine if an expiratory flow increase technique (EFIT) is associated with acid reflux episodes in infants born preterm with bronchopulmonary dysplasia (BPD). METHODS: A crossover study was carried out. Eighteen subjects divided into 2 groups were randomly assigned to receive 2 EFIT sessions at 2 postprandial time points. Group 1 started 2 hours after feeding and group 2 started 3 hours after feeding. Esophageal acid exposure was assessed by the reflux index (RI) during EFIT and 20 minutes before EFIT by esophageal pH monitoring. RESULTS: A significant reduction in the RI was observed in group 1 with EFIT performed 2 hours after feeding. Group 2 showed no significant differences in RI values before and during EFIT in both postprandial periods. CONCLUSION: When EFIT is performed 2 and 3 hours after feeding, it is not associated with an increase in acid reflux episodes in infants born preterm with BPD. PMID- 22090071 TI - Commentary on "Expiratory flow increase technique and acid esophageal exposure in infants born preterm with bronchopulmonary dysplasia". PMID- 22090072 TI - Factors influencing gross motor development in young children in an urban child welfare system. AB - PURPOSE: To determine whether young children involved with child welfare (CW) have gross motor (GM) delay; to examine relationships between GM skills and the influence of multiple factors on GM skills. METHODS: One hundred seventy-six children involved with CW received GM assessment, physical examinations, and caseworker interviews. Descriptive statistics, correlations, t tests, analysis of variance and covariance, and multiple regression analyses were completed. RESULTS: GM scores, lower than population norms, were associated with growth parameters. Children in kinship care had significantly higher GM scores compared with children in foster care and those with in-home protective services when adjusted for differences in time in CW. Abuse/neglect, medical neglect, and parental substance abuse produced lower scores; referral for abandonment produced higher scores. Age was most strongly related to GM outcome, with multiple regression explaining 19% of GM variance. CONCLUSION: Children involved with CW have lower mean GM scores than population norms. Several factors specific to CW experiences may influence GM outcome. PMID- 22090073 TI - Gross motor development in babies with treated idiopathic clubfoot. AB - PURPOSE: To investigate the effect of treated clubfoot disorder on gross motor skill level measured by the Alberta Infant Motor Scale (AIMS). METHODS: Fifty-two babies participated: 26 were treated for idiopathic clubfoot (12 with the Ponseti treatment method, 9 with the French physical therapy technique, and 5 with a combination of both methods); 26 were babies who were typically developing and without medical diagnoses. The AIMS was administered at 3-month intervals. RESULTS: No significant differences in AIMS scores were found between the clubfoot and control groups at 3 and 6 months, but at 9 and 12 months the clubfoot group scored significantly lower. Babies who were typically developing were significantly more likely to be walking at 12 months than babies with clubfoot. CONCLUSIONS: Treated clubfoot was associated with a mild delay in attainment of gross motor skills at 9 and 12 months of age. PMID- 22090074 TI - Commentary on "Gross motor development in babies with treated idiopathic clubfoot". PMID- 22090075 TI - Walking stride rate patterns in children and youth. AB - PURPOSE: To describe walking activity patterns in youth who are typically developing (TD) using a novel analysis of stride data and compare to youth with cerebral palsy (CP) and arthrogryposis (AR). METHOD: Stride rate curves were developed from 5 days of StepWatch data for 428 youth ages 2 to 16 years who were TD. RESULTS: Patterns of stride rates changed with age in the TD group (P = .03 to < .001). Inactivity varied with age (P < .001); peak stride rate decreased with age (P < .001). Curves were stable over a 2-week time frame (P = .38 to .95). Youth with CP and AR have lower stride rate patterns (P = .04 to .001). CONCLUSION: This is the first documentation of pediatric stride-rate patterns within the context of daily life. Including peak stride rates and levels of walking activity, this single visual format has potential clinical and research applications. PMID- 22090076 TI - Commentary on "Walking stride rate patterns in children and youth". PMID- 22090077 TI - Predictors of Standardized Walking Obstacle Course outcome measures in children with and without developmental disabilities. AB - PURPOSE: This study was designed to determine which characteristics of children predict measures on the Standardized Walking Obstacle Course (SWOC). METHODS: SWOC testing was performed under 3 conditions: (1) walk, (2) walk with a tray, and (3) walk wearing shaded glasses. Trials consisted of standing up, walking the course in 1 direction, and sitting down. Children (n = 440) completed 2 trials per condition. Trial measures included time, and numbers of steps, stumbles, and steps off the path. Relationships were evaluated using Chi-square analyses and significant predictors were determined by multiple logistic regression analyses. Sensitivity and specificity were calculated to determine the accuracy of disability as a predictor. RESULTS: Age, weight, and disability were the strongest predictors (P < .05). Increased age and weight predicted shorter time and fewest steps. Disability predicts longer time and most steps. CONCLUSION: The SWOC is appropriate to screen children for disabilities in functional ambulation. PMID- 22090078 TI - Commentary on "Predictors of Standardized Walking Obstacle Course outcome measures in children with and without developmental disabilities". PMID- 22090079 TI - Feasibility study: the effect of therapeutic yoga on quality of life in children hospitalized with cancer. AB - PURPOSE: To describe the effect of therapeutic yoga on child and parental reports of quality of life in children hospitalized with oncological diagnoses. METHODS: Six children participated in 5 yoga sessions over 2 months. The PedsQL 4.0 was administered to each child and participating parent/caregivers at baseline and after completion of the yoga intervention. The Wilcoxon nonparametric rank test measured individual differences over time. RESULTS: Statistically significant differences (P < .05) were found in child perception of gross motor function. CONCLUSION: These feasibility study data suggest that therapeutic yoga positively affected child perception of gross motor function measured on the PedsQL 4.0. Further studies are needed, including a randomized control trial and with a larger number of participants, to clarify and confirm the effect of therapeutic yoga. PMID- 22090080 TI - Commentary on "Feasibility study: effects of therapeutic yoga on quality of life in children hospitalized with cancer". PMID- 22090081 TI - Pediatric physical therapists' use of support walkers for children with disabilities: a nationwide survey. AB - PURPOSE: This study investigated pediatric physical therapists' use of support walkers (SWs) for children with disabilities. METHODS: An 8-page survey was mailed to 2500 randomly selected members of the Section on Pediatrics of the American Physical Therapy Association. Respondents to the survey included 513 pediatric physical therapists who were users of SWs. Descriptive statistics were calculated and themes were analyzed. RESULTS: Several SWs were reported as used most often to improve gait, mobility, participation at school, and interaction with peers. Use commonly included a month trial before purchase and 9 sessions of physical therapy to train a child for use in school. Reasons given for the use of SWs were improving impairments, functional limitations, and participation with peers. CONCLUSIONS: Pediatric physical therapists use SWs to increase postural control, mobility, and children's participation in school. PMID- 22090082 TI - Commentary on "Pediatric physical therapists' use of support walkers for children with disabilities: a nationwide survey". PMID- 22090083 TI - Continued ambulation gains through high school in a student with cerebral palsy: a case report. AB - PURPOSE: The purpose of this case report is to describe school-based physical therapy services received throughout high school by a student with diplegic cerebral palsy and to share her functional gains. KEY POINTS: This previously discharged 15-year-old freshman was re-referred due to a perceived walking regression using long-leg braces/reverse rolling walker and her desire to again try crutches. She subsequently resumed walking, typically 4 days per week at school and progressed to axillary crutches on level surfaces and stairs. Gross Motor Function Measure scores increased from 66.4% freshman year to 78.8% senior year, with the greatest dimension changes in standing (35.9%-69.2%) and walking, running, and jumping (8.3%-25.0%). CONCLUSION: School-based physical therapists are uniquely positioned to work with students in natural environments to optimize activity and participation. This report shows that continued ambulation gains in individuals with cerebral palsy are possible throughout adolescence. PMID- 22090084 TI - Power mobility and socialization in preschool: follow-up case study of a child with cerebral palsy. AB - PURPOSE: Our previous study found it feasible for a preschooler with cerebral palsy (CP) to use a power mobility device in his classroom but noted a lack of typical socialization. The purpose of this follow-up study was to determine the feasibility of providing mobility and socialization training for this child. METHODS: Will, a 3-year-old with CP, 1 comparison peer, 2 preschool teachers, and 2 therapists were filmed daily during a training and posttraining phase. Adult directed training was provided in the classroom by therapists and teachers during the training phase. Mobility and socialization measures were coded from video. OUTCOMES: During training, Will demonstrated greater socialization but less mobility than the comparison peer. Posttraining, Will socialized less but was more mobile, though less mobile than the comparison peer. DISCUSSION: Short-term, adult-directed power mobility and socialization training appear feasible for the preschool classroom. Important issues regarding socialization and power mobility are discussed. PMID- 22090087 TI - [Ocular hypertension. What is it actually?]. PMID- 22090088 TI - [Recommendations for follow-up examinations in patients with ocular hypertension]. AB - Ocular hypertension (OHT) describes a condition with elevated intraocular pressure (IOP) above the norm ( > 21 mmHg). By definition the anterior chamber angle is open and there are neither signs of glaucomatous optic nerve damage nor visual field defects. Thus, for the diagnosis of OHT an extensive baseline examination is mandatory in order to rule out pre-existing glaucomatous damage. Patients with ocular hypertension are at a higher risk of developing glaucoma. Therefore, periodical routine examinations with a standardized protocol for specific follow-up examinations are highly recommended. PMID- 22090089 TI - [Orbital exenteration. Algorithm for therapy and rehabilitation]. AB - Various procedures are available for orbital exenteration, mostly for neoplastic disorders, as well as for reconstructive surgery. Within the context of postoperative care prosthetic rehabilitation plays an important role. The specific form of planned epithetic replacement must already be considered in the design of the surgical procedure. PMID- 22090091 TI - [The 2011 Julius Springer prize for ophthalmology. Awarded to prof. Dr. Daniel Meller and Dr. Mikk Pauklin]. PMID- 22090090 TI - [Therapy options for chronic central serous chorioretinopathy. Photodynamic therapy combined with bevacizumab - a case series]. AB - BACKGROUND: This article reports about the use of a combined photodynamic therapy (PDT) and intravitreal injection of bevacizumab as a treatment option in nine patients with chronic central serous chorioretinopathy (CSC). PATIENTS AND METHODS: A total of nine male patients with chronic CSC were treated with standard PDT laser treatment with verteporfin and intravitreal injection of bevacizumab administered within 24 h. Before and 1, 3, 6, 9 and 12 months after treatment the results of visual acuity, fluorescein angiography (FA) and optical coherence tomography (OCT) examinations were documented. RESULTS: All patients showed an improvement in visual acuity of 1-4 ETDRS lines. Mean visual acuity increased from baseline 20 / 40 to 20 / 25 after 3 months. FA and OCT findings showed a restitution of leakages and subretinal fluid in all cases. After 6-12 months follow-up 8 patients had ongoing improvement in vision without recurrence of CSC. CONCLUSION: The combination of PDT with bevacizumab in this case series appears to be an effective and safe therapy combination which is suitable as a therapeutic option for patients with chronic CCS without a tendency to recovery. PMID- 22090092 TI - [Prophylaxis and therapy of postoperative endophthalmitis. Criticism of the ESCRS study and the Early Vitrectomy study]. AB - Postoperative endophthalmitis often leads to a substantial loss of vision and sometimes to loss of the eye. Occasionally this results in legal disputes during which medical studies will be consulted for reaching a verdict. Both the European Society of Cataract and Refractive Surgeons (ESCRS) study on prophylaxis and the Early Vitrectomy study on the therapy of postoperative endophthalmitis suffer from substantial deficits in essential areas. These studies cannot therefore be utilized as standard operating procedures and guidelines as well as in legal disputes. PMID- 22090093 TI - [Perioperative visual loss after nonocular surgery]. AB - Perioperative visual loss (POVL) after nonocular surgery is a rare but unexpected event and represents a devastating complication. It is most often associated with cardiac, spinal as well as head and neck surgery. The etiology of POVL remains incompletely understood. Any portion of the visual system may be involved, from the cornea to the occipital lobe. The most common site of permanent injury is, however, the optic nerve itself and ischemia is the most often presumed mechanism. Multiple factors have been proposed as risk factors for POVL, including long duration in the prone position, decreased ocular perfusion pressure, excessive blood loss and anemia, hypotension, hypoxia, excessive fluid replacement, elevated venous pressure, head positioning and a patient-specific vascular susceptibility which may be anatomic or physiologic. However, the risk factors for any given patient or procedure may vary. The underlying specific pathogenesis of these neuro-ophthalmic complications remains unknown and physicians should be alert to the potential for loss of vision in the postoperative period. This review updates readers on the incidence, suspected risk factors, diagnosis and treatment of POVL in the setting of nonocular surgery. PMID- 22090095 TI - Recovery of viable cells from rabbit skin biopsies after storage at -20 degrees C for up to 10 days. AB - Frozen animal tissues are thought to be appropriate for use as a donor for somatic cell nuclear transfer. This makes the freezing for long term storage a valuable tool for breeders needing to protect an animal population that is endangered by sanitary problems or for cryobanking of genetic resources. We report the successful cryopreservation of explants of skin derived from small biopsies from rabbit ear biopsies by using a protocol that can be easily performed by usual breeders, which are not equipped with cooling devices. By optimizing the procedure, we show that small biopsies can be kept at -20 degrees C in a physiological solution containing 10% DMSO for up to 20 days before being deeply frozen in liquid nitrogen for long-term storage. After 10 days of storage at -20 degrees C, the rate of viability of biopsies was similar to the control one (86 and 82% respectively). After 20 days of storage at -20 degrees C, the rate of viability was dramatically lowered (39%), but it still allows to recover a significant population of viable cells from the preserved sample. Being appropriate to places lacking specific device, such a very simple technique may contribute to facilitate genome banking policies dedicated to the management of genetic resources in wild and domestic animals. PMID- 22090096 TI - Innate sensing of foamy viruses by human hematopoietic cells. AB - Foamy viruses (FV) are nonpathogenic retroviruses that have cospeciated with primates for millions of years. FV can be transmitted through severe bites from monkeys to humans. Viral loads remain generally low in infected humans, and no secondary transmission has been reported. Very little is known about the ability of FV to trigger an innate immune response in human cells. A few previous reports suggested that FV do not induce type I interferon (IFN) in nonhematopoietic cells. Here, we examined how human hematopoietic cells sense FV particles and FV infected cells. We show that peripheral blood mononuclear cells (PBMCs), plasmacytoid dendritic cells (pDCs), and the pDC-like cell line Gen2.2 detect FV, produce high levels of type I IFN, and express the IFN-stimulated gene MxA. Fewer than 20 FV-infected cells are sufficient to trigger an IFN response. Both prototypic and primary viruses stimulated IFN release. Donor cells expressing a replication-defective virus, carrying a mutated reverse transcriptase, induced IFN production by target cells as potently as wild-type virus. In contrast, an FV strain with env deleted, which does not produce viral particles, was inactive. IFN production was blocked by an inhibitor of endosomal acidification (bafilomycin A1) and by an endosomal Toll-like receptor (TLR) antagonist (A151). Silencing experiments in Gen2.2 further demonstrated that TLR7 is involved in FV recognition. Therefore, FV are potent inducers of type I IFN by pDCs and by PBMCs. This previously underestimated activation of the innate immune response may be involved in the control of viral replication in humans. PMID- 22090097 TI - Transmembrane domain determinants of CD4 Downregulation by HIV-1 Vpu. AB - The transmembrane domains (TMDs) of integral membrane proteins do not merely function as membrane anchors but play active roles in many important biological processes. The downregulation of the CD4 coreceptor by the Vpu protein of HIV-1 is a prime example of a process that is dependent on specific properties of TMDs. Here we report the identification of Trp22 in the Vpu TMD and Gly415 in the CD4 TMD as critical determinants of Vpu-induced targeting of CD4 to endoplasmic reticulum (ER)-associated degradation (ERAD). The two residues participate in different aspects of ERAD targeting. Vpu Trp22 is required to prevent assembly of Vpu into an inactive, oligomeric form and to promote CD4 polyubiquitination and subsequent recruitment of the VCP-UFD1L-NPL4 dislocase complex. In the presence of a Vpu Trp22 mutant, CD4 remains integrally associated with the ER membrane, suggesting that dislocation from the ER into the cytosol is impaired. CD4 Gly415, on the other hand, contributes to CD4-Vpu interactions. We also identify two residues, Val20 and Ser23, in the Vpu TMD that mediate retention of Vpu and, by extension, CD4 in the ER. These findings highlight the exploitation of several TMD-mediated mechanisms by HIV-1 Vpu in order to downregulate CD4 and thus promote viral pathogenesis. PMID- 22090098 TI - Monoclonal antibody-based antigenic mapping of norovirus GII.4-2002. AB - Noroviruses are the primary cause of epidemic gastroenteritis in humans, and GII.4 strains cause ~80% of the overall disease burden. Surrogate neutralization assays using sera and mouse monoclonal antibodies (MAbs) suggest that antigenic variation maintains GII.4 persistence in the face of herd immunity, as the emergence of new pandemic strains is accompanied by newly evolved neutralization epitopes. To potentially identify specific blockade epitopes that are likely neutralizing and evolving between pandemic strains, mice were hyperimmunized with GII.4-2002 virus-like particles (VLPs) and the resulting MAbs were characterized by biochemical and immunologic assays. All of the MAbs but one recognized GII.4 VLPs representing strains circulating from 1987 to 2009. One MAb weakly recognized GII.4-1987 and -1997 while strongly interacting with 2002 VLPs. This antibody was highly selective and effective at blocking only GII.4-2002-ligand binding. Using bioinformatic analyses, we predicted an evolving GII.4 surface epitope composed of amino acids 407, 412, and 413 and subsequently built mutant VLPs to test the impact of the epitope on MAb binding and blockade potential. Replacement of the 2002 epitope with the epitopes found in 1987 or 2006 strains either reduced or ablated enzyme immunoassay recognition by the GII.4-2002 specific blockade MAb. These data identify a novel, evolving blockade epitope that may be associated with protective immunity, providing further support for the hypotheses that GII.4 norovirus evolution results in antigenic variation that allows the virus to escape from protective herd immunity, resulting in new epidemic strains. PMID- 22090099 TI - Dynamics of simian immunodeficiency virus SIVmac239 infection in pigtail macaques. AB - Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4(+) T cell depletion, as CD4(+) T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression. PMID- 22090100 TI - Mucosal and peripheral Lin- HLA-DR+ CD11c/123- CD13+ CD14- mononuclear cells are preferentially infected during acute simian immunodeficiency virus infection. AB - Massive infection of memory CD4 T cells is a hallmark of early simian immunodeficiency virus (SIV) infection, with viral infection peaking at day 10 postinfection (p.i.), when a majority of memory CD4 T cells in mucosal and peripheral tissues are infected. It is not clear if mononuclear cells from the monocyte and macrophage lineages are similarly infected during this early phase of explosive HIV and SIV infections. Here we show that, at day 10 p.i., Lin(-) HLA-DR(+) CD11c/123(-) CD13(+) CD14(-) macrophages in the jejunal mucosa were infected, albeit at lower levels than CD4 memory T cells. Interestingly, Lin(-) HLA-DR(+) CD11c/123(-) CD13(+) CD14(-) macrophages in peripheral blood, like their mucosal counterparts, were preferentially infected compared to Lin(-) HLA DR(+) CD11c/123(-) CD13(+) CD14(+) monocytes, suggesting that differentiated macrophages were selectively infected by SIV. CD13(+) CD14(-) macrophages expressed low levels of CD4 compared to CD4 T cells but expressed similar levels of CCR5 as lymphocytes. Interestingly, CD13(+) CD14(-) macrophages expressed Apobec3G at lower levels than CD13(+) CD14(+) monocytes, suggesting that intracellular restriction may contribute to the differential infection of mononuclear subsets. Taken together, our results suggest that CD13(+) CD14(-) macrophages in mucosal and peripheral tissues are preferentially infected very early during the course of SIV infection. PMID- 22090101 TI - Marked endotheliotropism of highly pathogenic avian influenza virus H5N1 following intestinal inoculation in cats. AB - Highly pathogenic avian influenza virus (HPAIV) H5N1 can infect mammals via the intestine; this is unusual since influenza viruses typically infect mammals via the respiratory tract. The dissemination of HPAIV H5N1 following intestinal entry and associated pathogenesis are largely unknown. To assess the route of spread of HPAIV H5N1 to other organs and to determine its associated pathogenesis, we inoculated infected chicken liver homogenate directly into the intestine of cats by use of enteric-coated capsules. Intestinal inoculation of HPAIV H5N1 resulted in fatal systemic disease. The spread of HPAIV H5N1 from the lumen of the intestine to other organs took place via the blood and lymphatic vascular systems but not via neuronal transmission. Remarkably, the systemic spread of the virus via the vascular system was associated with massive infection of endothelial and lymphendothelial cells, resulting in widespread hemorrhages. This is unique for influenza in mammals and resembles the pathogenesis of HPAIV infection in terrestrial poultry. It contrasts with the pathogenesis of systemic disease from the same virus following entry via the respiratory tract, where lesions are characterized mainly by necrosis and inflammation and are associated with the presence of influenza virus antigen in parenchymal, not endothelial cells. The marked endotheliotropism of the virus following intestinal inoculation indicates that the pathogenesis of systemic influenza virus infection in mammals may differ according to the portal of entry. PMID- 22090102 TI - Bromovirus RNA replication compartment formation requires concerted action of 1a's self-interacting RNA capping and helicase domains. AB - All positive-strand RNA viruses replicate their genomes in association with rearranged intracellular membranes such as single- or double-membrane vesicles. Brome mosaic virus (BMV) RNA synthesis occurs in vesicular endoplasmic reticulum (ER) membrane invaginations, each induced by many copies of viral replication protein 1a, which has N-terminal RNA capping and C-terminal helicase domains. Although the capping domain is responsible for 1a membrane association and ER targeting, neither this domain nor the helicase domain was sufficient to induce replication vesicle formation. Moreover, despite their potential for mutual interaction, the capping and helicase domains showed no complementation when coexpressed in trans. Cross-linking showed that the capping and helicase domains each form trimers and larger multimers in vivo, and the capping domain formed extended, stacked, hexagonal lattices in vivo. Furthermore, coexpressing the capping domain blocked the ability of full-length 1a to form replication vesicles and replicate RNA and recruited full-length 1a into mixed hexagonal lattices with the capping domain. Thus, BMV replication vesicle formation and RNA replication depend on the direct linkage and concerted action of 1a's self-interacting capping and helicase domains. In particular, the capping domain's strong dominant negative effects showed that the ability of full-length 1a to form replication vesicles was highly sensitive to disruption by non-productively titrating lattice forming self-interactions of the capping domain. These and other findings shed light on the roles and interactions of 1a domains in replication compartment formation and support prior results suggesting that 1a induces replication vesicles by forming a capsid-like interior shell. PMID- 22090103 TI - Hepatitis C virus fails to activate NF-kappaB signaling in plasmacytoid dendritic cells. AB - Plasmacytoid dendritic cells (pDCs) respond to viral infection by production of alpha interferon (IFN-alpha), proinflammatory cytokines, and cell differentiation. The elimination of hepatitis C virus (HCV) in more than 50% of chronically infected patients by treatment with IFN-alpha suggests that pDCs can play an important role in the control of HCV infection. pDCs exposed to HCV infected hepatoma cells, in contrast to cell-free HCV virions, produce large amounts of IFN-alpha. To further investigate the molecular mechanism of HCV sensing, we studied whether exposure of pDCs to HCV-infected hepatoma cells activates, in parallel to interferon regulatory factor 7 (IRF7)-mediated production of IFN-alpha, nuclear factor kappa B (NF-kappaB)-dependent pDC responses, such as expression of the differentiation markers CD40, CCR7, CD86, and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and secretion of the proinflammatory cytokines TNF-alpha and interleukin 6 (IL-6). We demonstrate that exposure of pDCs to HCV-infected hepatoma cells surprisingly did not induce phosphorylation of NF-kappaB or cell surface expression of CD40, CCR7, CD86, or TRAIL or secretion of TNF-alpha and IL-6. In contrast, CpG-A and CpG-B induced production of TNF-alpha and IL-6 in pDCs exposed to the HCV-infected hepatoma cells, showing that cell-associated virus did not actively inhibit Toll like receptor (TLR)-mediated NF-kappaB phosphorylation. Our results suggest that cell-associated HCV signals in pDCs via an endocytosis-dependent mechanism and IRF7 but not via the NF-kappaB pathway. In spite of IFN-alpha induction, cell associated HCV does not induce a full functional response of pDCs. These findings contribute to the understanding of evasion of immune responses by HCV. PMID- 22090104 TI - Significant association of multiple human cytomegalovirus genomic Loci with glioblastoma multiforme samples. AB - Viruses are appreciated as etiological agents of certain human tumors, but the number of different cancer types induced or exacerbated by viral infections is unknown. Glioblastoma multiforme (GBM)/astrocytoma grade IV is a malignant and lethal brain cancer of unknown origin. Over the past decade, several studies have searched for the presence of a prominent herpesvirus, human cytomegalovirus (HCMV), in GBM samples. While some have detected HCMV DNA, RNA, and proteins in GBM tissues, others have not. Therefore, any purported association of HCMV with GBM remains controversial. In most of the previous studies, only one or a select few viral targets were analyzed. Thus, it remains unclear the extent to which the entire viral genome was present when detected. Here we report the results of a survey of GBM specimens for as many as 20 different regions of the HCMV genome. Our findings indicate that multiple HCMV loci are statistically more likely to be found in GBM samples than in other brain tumors or epileptic brain specimens and that the viral genome was more often detected in frozen samples than in paraffin embedded archival tissue samples. Finally, our experimental results indicate that cellular genomes substantially outnumber viral genomes in HCMV-positive GBM specimens, likely indicating that only a minority of the cells found in such samples harbor viral DNA. These data argue for the association of HCMV with GBM, defining the virus as oncoaccessory. Furthermore, they imply that, were HCMV to enhance the growth or survival of a tumor (i.e., if it is oncomodulatory), it would likely do so through mechanisms distinct from classic tumor viruses that express transforming viral oncoproteins in the overwhelming majority of tumor cells. PMID- 22090105 TI - HLA-B*57 Micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control. AB - The genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B*57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B*57 alleles and the closely related HLA-B*5801 are often grouped together because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B*57 alleles, termed HLA-B*57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C-clade-infected subjects from southern Africa, HLA-B*5703 is associated with a lower viral-load set point than HLA-B*5702 and HLA-B*5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma; P = 0.24 and P = 0.0005). In order to better understand these observed differences in HLA B*57/5801-mediated immune control of HIV, we undertook, in a study of >1,000 C clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both by unique CD8(+) T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8(+) T-cell responses and immune selection pressures for which these protective alleles are responsible. These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8(+) T-cell responses generated that can drive significant selection pressure on the virus. PMID- 22090106 TI - Duck Hepatitis A virus possesses a distinct type IV internal ribosome entry site element of picornavirus. AB - Sequence analysis of duck hepatitis virus type 1 (DHV-1) led to its classification as the only member of a new genus, Avihepatovirus, of the family Picornaviridae, and so was renamed duck hepatitis A virus (DHAV). The 5' untranslated region (5' UTR) plays an important role in translation initiation and RNA synthesis of the picornavirus. Here, we provide evidence that the 651 nucleotide (nt)-long 5' UTR of DHAV genome contains an internal ribosome entry site (IRES) element that functions efficiently in vitro and within BHK cells. Comparative sequence analysis showed that the 3' part of the DHAV 5' UTR is similar to the porcine teschovirus 1 (PTV-1) IRES in sequence and predicted secondary structure. Further mutational analyses of the predicted domain IIId, domain IIIe, and pseudoknot structure at the 3' end of the DHAV IRES support our predicted secondary structure. However, unlike the case for the PTV-1 IRES element, analysis of various deletion mutants demonstrated that the optimally functional DHAV IRES element with a size of approximately 420 nt is larger than that of PTV-1 and contains other peripheral domains (Id and Ie) that do not exist within the type IV IRES elements. The domain Ie, however, could be removed without significant loss of activity. Surprisingly, like the hepatitis A virus (HAV) IRES element, the activity of DHAV IRES could be eliminated by expression of enterovirus 2A protease. These findings indicate that the DHAV IRES shares common features with type IV picornavirus IRES elements, whereas it exhibits significant differences from type IV IRESs. Therefore, we propose that DHAV possesses a distinct type IV IRES element of picornavirus. PMID- 22090107 TI - Cloning and analysis of sooty mangabey alternative coreceptors that support simian immunodeficiency virus SIVsmm entry independently of CCR5. AB - Natural host sooty mangabeys (SM) infected with simian immunodeficiency virus SIVsmm do not develop AIDS despite high viremia. SM and other natural hosts express very low levels of CCR5 on CD4(+) T cells, and we recently showed that SIVsmm infection and robust replication occur in vivo in SM genetically lacking CCR5, indicating the use of additional entry pathways. SIVsmm uses several alternative coreceptors of human origin in vitro, but which molecules of SM origin support entry is unknown. We cloned a panel of putative coreceptors from SM and tested their ability to mediate infection, in conjunction with smCD4, by pseudotypes carrying Envs from multiple SIVsmm subtypes. smCXCR6 supported efficient infection by all SIVsmm isolates with entry levels comparable to those for smCCR5, and smGPR15 enabled entry by all isolates at modest levels. smGPR1 and smAPJ supported low and variable entry, whereas smCCR2b, smCCR3, smCCR4, smCCR8, and smCXCR4 were not used by most isolates. In contrast, SIVsmm from rare infected SM with profound CD4(+) T cell loss, previously reported to have expanded use of human coreceptors, including CXCR4, used smCXCR4, smCXCR6, and smCCR5 efficiently and also exhibited robust entry through smCCR3, smCCR8, smGPR1, smGPR15, and smAPJ. Entry was similar with both known alleles of smCD4. These alternative coreceptors, particularly smCXCR6 and smGPR15, may support virus replication in SM that have restricted CCR5 expression as well as SM genetically lacking CCR5. Defining expression of these molecules on SM CD4(+) subsets may delineate distinct natural host target cell populations capable of supporting SIVsmm replication without CD4(+) T cell loss. PMID- 22090108 TI - The virion-associated open reading frame 49 of murine gammaherpesvirus 68 promotes viral replication both in vitro and in vivo as a derepressor of RTA. AB - Replication and transcription activator (RTA), an immediate-early gene, is a key molecular switch to evoke lytic replication of gammaherpesviruses. Open reading frame 49 (ORF49) is conserved among gammaherpesviruses and shown to cooperate with RTA in regulating virus lytic replication. Here we show a molecular mechanism and in vivo functions of murine gammaherpesvirus 68 (MHV-68 or gammaHV 68) ORF49. MHV-68 ORF49 was transcribed and translated as a late gene. The ORF49 protein was associated with a virion, interacting with the ORF64 large tegument protein and the ORF25 capsid protein. Moreover, ORF49 directly bound to RTA and its negative cellular regulator, poly(ADP-ribose) polymerase-1 (PARP-1), and disrupted the interactions of RTA and PARP-1. Productive replication of an ORF49 deficient mutant virus (49S) was attenuated in vivo as well as in vitro. Likewise, latent infection was also impaired in the spleen of 49S-infected mice. Taken together, our results suggest that the virion-associated ORF49 protein may promote virus replication both in vitro and in vivo by providing an optimal environment in the early phase of virus infection as a derepressor of RTA. PMID- 22090109 TI - Naturally occurring fragments from two distinct regions of the prostatic acid phosphatase form amyloidogenic enhancers of HIV infection. AB - Semen is the major vector for HIV-1 transmission. We previously isolated C proximal fragments of the prostatic acid phosphatase (PAP) from semen which formed amyloid fibrils that potently enhanced HIV infection. Here, we used the same methodology and identified another amyloidogenic peptide. Surprisingly, this peptide is derived from an N-proximal fragment of PAP (PAP85-120) and forms, similar to the C-proximal fragments, positively charged fibrillar structures that increase virion attachment to cells. Our results provide a first example for amyloid formation by fragments of distinct regions of the same precursor and further emphasize the possible importance of amyloidogenic peptides in HIV transmission. PMID- 22090110 TI - Genetic mapping of a highly variable norovirus GII.4 blockade epitope: potential role in escape from human herd immunity. AB - Noroviruses account for 96% of viral gastroenteritis cases worldwide, with GII.4 strains responsible >80% of norovirus outbreaks. Histo-blood group antigens (HBGAs) are norovirus binding ligands, and antigenic and preferential HBGA binding profiles vary over time as new GII.4 strains emerge. The capsid P2 subdomain facilitates HBGA binding, contains neutralizing antibody epitopes, and likely evolves in response to herd immunity. To identify amino acids regulating HBGA binding and antigenic differences over time, we created chimeric virus-like particles (VLPs) between the GII.4-1987 and GII.4-2006 strains by exchanging amino acids in putative epitopes and characterized their antigenic and HBGA binding profiles using anti-GII.4-1987 and -2006 mouse monoclonal antibodies (MAbs) and polyclonal sera, 1988 outbreak human sera, and synthetic HBGAs. The exchange of amino acids 393 to 395 between GII.4-1987 and GII.4-2006 resulted in altered synthetic HBGA binding compared to parental strains. Introduction of GII.4-1987 residues 294, 297 to 298, 368, and 372 (epitope A) into GII.4-2006 resulted in reactivity with three anti-GII.4-1987 MAbs and reduced reactivity with four anti-GII.4-2006 MAbs. The three anti-GII.4-1987 MAbs also blocked chimeric VLP-HBGA interaction, while an anti-GII.4-2006 blocking antibody did not, indicating that epitope A amino acids comprise a potential neutralizing epitope for GII.4-1987 and GII.4-2006. We also tested GII.4-1987-immunized mouse polyclonal sera and 1988 outbreak human sera for the ability to block chimeric VLP-HBGA interaction and found that epitope A amino acids contribute significantly to the GII.4-1987 blockade response. Our data provide insights that help explain the emergence of new GII.4 epidemic strains over time, may aid development of norovirus therapeutics, and may help predict the emergence of future epidemic strains. PMID- 22090111 TI - Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen induction by hypoxia and hypoxia-inducible factors. AB - Hypoxia and hypoxia-inducible factors (HIFs) play an important role in the Kaposi's sarcoma-associated herpesvirus (KSHV) life cycle. In particular, hypoxia can activate lytic replication of KSHV and specific lytic genes, including the replication and transcription activator (RTA), while KSHV infection in turn can increase the levels and activity of HIFs. In the present study, we show that hypoxia increases the levels of mRNAs encoding KSHV latency-associated nuclear antigen (LANA) in primary effusion lymphoma (PEL) cell lines and also increases the levels of LANA protein. Luciferase reporter assays in Hep3B cells revealed a moderate activation of the LANA promoter region by hypoxia as well as by cotransfection with degradation-resistant HIF-1alpha or HIF-2alpha expression plasmids. Computer analysis of a 1.2-kb sequence upstream of the LANA translational start site identified six potential hypoxia-responsive elements (HRE). Sequential deletion studies revealed that much of this activity was mediated by one of these HREs (HRE 4R) oriented in the 3' to 5' direction and located between the constitutive (LTc) and RTA-inducible (LTi) mRNA start sites. Site-directed mutation of this HRE substantially reduced the response to both HIF 1alpha and HIF-2alpha in a luciferase reporter assay. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated binding of both HIF-1alpha and HIF-2alpha to this region. Also, HIF-1alpha was found to associate with RTA, and HIFs enhanced the activation of LTi by RTA. These results provide evidence that hypoxia and HIFs upregulate both latent and lytic KSHV replication and play a central role in the life cycle of this virus. PMID- 22090112 TI - Varicella-zoster virus inhibition of the NF-kappaB pathway during infection of human dendritic cells: role for open reading frame 61 as a modulator of NF-kappaB activity. AB - Dendritic cells (DC) are antigen-presenting cells essential for initiating primary immune responses and therefore an ideal target for viral immune evasion. Varicella-zoster virus (VZV) can productively infect immature human DCs and impair their function as immune effectors by inhibiting their maturation, as evidenced by the expression modulation of functionally important cell surface immune molecules CD80, CD86, CD83, and major histocompatibility complex I. The NF kappaB pathway largely regulates the expression of these immune molecules, and therefore we sought to determine whether VZV infection of DCs modulates the NF kappaB pathway. Nuclear localization of NF-kappaB p50 and p65 indicates pathway activation; however, immunofluorescence studies revealed cytoplasmic retention of these NF-kappaB subunits in VZV-infected DCs. Western blotting revealed phosphorylation of the inhibitor of kappaBalpha (IkappaBalpha) in VZV-infected DCs, indicating that the pathway is active at this point. We conclude that VZV infection of DC inhibits the NF-kappaB pathway following protein phosphorylation but before the translocation of NF-kappaB subunits into the nucleus. An NF-kappaB reporter assay identified VZV open reading frame 61 (ORF61) as an inhibitor of tumor necrosis factor alpha-induced NF-kappaB reporter activity. Mutational analysis of ORF61 identified the E3 ubiquitin ligase domain as a region required for NF-kappaB pathway inhibition. In summary, we provide evidence that VZV inhibits the NF-kappaB signaling pathway in human DCs and that the E3 ubiquitin ligase domain of ORF61 is required to modulate this pathway. Thus, this work identifies a mechanism by which VZV modulates host immune function. PMID- 22090113 TI - The cellular chaperone hsc70 is specifically recruited to reovirus viral factories independently of its chaperone function. AB - Mammalian orthoreoviruses replicate and assemble in the cytosol of infected cells. A viral nonstructural protein, MUNS, forms large inclusion-like structures called viral factories (VFs) in which assembling viral particles can be identified. Here we examined the localization of the cellular chaperone Hsc70 and found that it colocalizes with VFs in infected cells and also with viral factory like structures (VFLs) formed by ectopically expressed MUNS. Small interfering RNA (siRNA)-mediated knockdown of Hsc70 did not affect the formation or maintenance of VFLs. We further showed that dominant negative mutants of Hsc70 were also recruited to VFLs, indicating that Hsc70 recruitment to VFLs is independent of the chaperone function. In support of this finding, MUNS was immunoprecipitated with wild-type Hsc70, with a dominant negative mutant of Hsc70, and with the minimal substrate-binding site of Hsc70 (amino acids 395 to 540). We identified a minimal region of MUNS between amino acids 222 and 271 that was sufficient for the interaction with Hsc70. This region of MUNS has not been assigned any function previously. However, neither point mutants with alterations in this region nor the complete deletion of this domain abrogated the MUNS-Hsc70 interaction, indicating that a second portion of MUNS also interacts with Hsc70. Taken together, these findings suggest a specific chaperone function for Hsc70 within viral factories, the sites of reovirus replication and assembly in cells. PMID- 22090114 TI - Migration of Norway rats resulted in the worldwide distribution of Seoul hantavirus today. AB - Despite the worldwide distribution, most of the known Seoul viruses (SEOV) are closely related to each other. In this study, the M and the S segment sequences of SEOV were recovered from 130 lung tissue samples (mostly of Norway rats) and from six patient serum samples by reverse transcription-PCR. Genetic analysis revealed that all sequences belong to SEOV and represent 136 novel strains. Phylogenetic analysis of all available M and S segment sequences of SEOV, including 136 novel Chinese strains, revealed four distinct groups. All non Chinese SEOV strains and most of the Chinese variants fell into the phylogroup A, while the Chinese strains originating from mountainous areas clustered into three other distinct groups (B, C, and D). We estimated that phylogroup A viruses may have arisen only within the last several centuries. All non-Chinese variants appeared to be directly originated from China. Thus, phylogroup A viruses distributed worldwide may share a recent ancestor, whereas SEOV seems to be as diversified genetically as other hantaviruses. In addition, all available mitochondrial DNA (mtDNA) sequences of Norway rats, including our 44 newly recovered mtDNA sequences, were divided into two phylogenetic groups. The first group, which is associated with the group A SEOV variants, included most of rats from China and also all non-Chinese rats, while the second group consisted of a few rats originating only from mountain areas in China. We hypothesize that an ancestor of phylogroup A SEOV variants was first exported from China to Europe and then spread through the New World following the migration of Norway rats. PMID- 22090115 TI - Adaptation of a duck influenza A virus in quail. AB - Quail are thought to serve as intermediate hosts of influenza A viruses between aquatic birds and terrestrial birds, such as chickens, due to their high susceptibility to aquatic-bird viruses, which then adapt to replicate efficiently in their new hosts. However, does replication of aquatic-bird influenza viruses in quail similarly result in their efficient replication in humans? Using sialic acid-galactose linkage-specific lectins, we found both avian (sialic acid-alpha2 3-galactose [Siaalpha2-3Gal] linkages on sialyloligosaccharides)--and human (Siaalpha2-6Gal)-type receptors on the tracheal cells of quail, consistent with previous reports. We also passaged a duck H3N2 virus in quail 19 times. Sequence analysis revealed that eight mutations accumulated in hemagglutinin (HA) during these passages. Interestingly, many of the altered HA amino acids found in the adapted virus are present in human seasonal viruses, but not in duck viruses. We also found that stepwise stalk deletion of neuraminidase occurred during passages, resulting in reduced neuraminidase function. Despite some hemagglutinin mutations near the receptor binding pocket, appreciable changes in receptor specificity were not detected. However, reverse-genetics-generated viruses that possessed the hemagglutinin and neuraminidase of the quail-passaged virus replicated significantly better than the virus possessing the parent HA and neuraminidase in normal human bronchial epithelial cells, whereas no significant difference in replication between the two viruses was observed in duck cells. Further, the quail-passaged but not the original duck virus replicated in human bronchial epithelial cells. These data indicate that quail can serve as intermediate hosts for aquatic-bird influenza viruses to be transmitted to humans. PMID- 22090116 TI - Lack of association between HLA class II alleles and in vitro replication capacities of recombinant viruses encoding HIV-1 subtype C Gag-protease from chronically infected individuals. AB - It is unknown whether favorable HLA class II alleles may attenuate HIV-1 through selection pressure in a manner similar to that of protective HLA class I alleles. We investigated the relationship between HLA class II alleles and in vitro replication capacities of recombinant viruses encoding HIV-1 subtype C Gag protease from chronically infected individuals. No associations were found between individual alleles and lower replication capacity, suggesting no significant HIV-1 attenuation by HLA class II-restricted Gag-specific CD4(+) T cell immune pressure. PMID- 22090117 TI - HIV-1 clinical isolates resistant to CCR5 antagonists exhibit delayed entry kinetics that are corrected in the presence of drug. AB - HIV CCR5 antagonists select for env gene mutations that enable virus entry via drug-bound coreceptor. To investigate the mechanisms responsible for viral adaptation to drug-bound coreceptor-mediated entry, we studied viral isolates from three participants who developed CCR5 antagonist resistance during treatment with vicriviroc (VCV), an investigational small-molecule CCR5 antagonist. VCV sensitive and -resistant viruses were isolated from one HIV subtype C- and two subtype B-infected participants; VCV-resistant isolates had mutations in the V3 loop of gp120 and were cross-resistant to TAK-779, an investigational antagonist, and maraviroc (MVC). All three resistant isolates contained a 306P mutation but had variable mutations elsewhere in the V3 stem. We used a virus-cell beta lactamase (BlaM) fusion assay to determine the entry kinetics of recombinant viruses that incorporated full-length VCV-sensitive and -resistant envelopes. VCV resistant isolates exhibited delayed entry rates in the absence of drug, relative to pretherapy VCV-sensitive isolates. The addition of drug corrected these delays. These findings were generalizable across target cell types with a range of CD4 and CCR5 surface densities and were observed when either population derived or clonal envelopes were used to construct recombinant viruses. V3 loop mutations alone were sufficient to restore virus entry in the presence of drug, and the accumulation of V3 mutations during VCV therapy led to progressively higher rates of viral entry. We propose that the restoration of pre-CCR5 antagonist therapy HIV entry kinetics drives the selection of V3 loop mutations and may represent a common mechanism that underlies the emergence of CCR5 antagonist resistance. PMID- 22090118 TI - Cooperation between viral interferon regulatory factor 4 and RTA to activate a subset of Kaposi's sarcoma-associated herpesvirus lytic promoters. AB - The four Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded interferon (IFN) regulatory factor homologues (vIRF1 to vIRF4) are used to counter innate immune defenses and suppress p53. The vIRF genes are arranged in tandem but differ in function and expression. In KSHV-infected effusion lymphoma lines, K10.5/vIRF3 and K11/vIRF2 mRNAs are readily detected during latency, whereas K9/vIRF1 and K10/vIRF4 mRNAs are upregulated during reactivation. Here we show that the K10/vIRF4 promoter responds to the lytic switch protein RTA in KSHV-infected cells but is essentially unresponsive in uninfected cells. Coexpression of RTA with vIRF4 is sufficient to restore regulation, a property not shared by other vIRFs. The K9/vIRF1 promoter behaves similarly, and production of infectious virus is enhanced by the presence of vIRF4. Synergy requires the DNA-binding domain (DBD) and C-terminal IRF homology regions of vIRF4. Mutations of arginine residues within the putative DNA recognition helix of vIRF4 or the invariant cysteines of the adjacent CxxC motif abolish cooperation with RTA, in the latter case by preventing self-association. The oligomerization and transactivation functions of RTA are also essential for synergy. The K10/vIRF4 promoter contains two transcription start sites (TSSs), and a 105-bp fragment containing the proximal promoter is responsive to vIRF4/RTA. Binding of a cellular factor(s) to this fragment is altered when both viral proteins are present, suggesting a possible mechanism for transcriptional synergy. Reliance on coregulators encoded by either the host or viral genome provides an elegant strategy for expanding the regulatory potential of a master regulator, such as RTA. PMID- 22090119 TI - High-resolution analysis of intrahost genetic diversity in dengue virus serotype 1 infection identifies mixed infections. AB - Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples (n = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia. PMID- 22090121 TI - Highly pathogenic avian influenza virus subtype H5N1 escaping neutralization: more than HA variation. AB - Influenza A viruses are one of the major threats in modern health care. Novel viruses arise due to antigenic drift and antigenic shift, leading to escape from the immune system and resulting in a serious problem for disease control. In order to investigate the escape process and to enable predictions of escape, we serially passaged influenza A H5N1 virus in vitro 100 times under immune pressure. The generated escape viruses were characterized phenotypically and in detail by full-genome deep sequencing. Mutations already found in natural isolates were detected, evidencing the in vivo relevance of the in vitro-induced amino acid substitutions. Additionally, several novel alterations were triggered. Altogether, the results imply that our in vitro system is suitable to study influenza A virus evolution and that it might even be possible to predict antigenic changes of influenza A viruses circulating in vaccinated populations. PMID- 22090120 TI - In vitro assembly of virus-like particles of a gammaretrovirus, the murine leukemia virus XMRV. AB - Immature retroviral particles are assembled by self-association of the structural polyprotein precursor Gag. During maturation the Gag polyprotein is proteolytically cleaved, yielding mature structural proteins, matrix (MA), capsid (CA), and nucleocapsid (NC), that reassemble into a mature viral particle. Proteolytic cleavage causes the N terminus of CA to fold back to form a beta hairpin, anchored by an internal salt bridge between the N-terminal proline and the inner aspartate. Using an in vitro assembly system of capsid-nucleocapsid protein (CANC), we studied the formation of virus-like particles (VLP) of a gammaretrovirus, the xenotropic murine leukemia virus (MLV)-related virus (XMRV). We show here that, unlike other retroviruses, XMRV CA and CANC do not assemble tubular particles characteristic of mature assembly. The prevention of beta hairpin formation by the deletion of either the N-terminal proline or 10 initial amino acids enabled the assembly of DeltaProCANC or Delta10CANC into immature like spherical particles. Detailed three-dimensional (3D) structural analysis of these particles revealed that below a disordered N-terminal CA layer, the C terminus of CA assembles a typical immature lattice, which is linked by rod-like densities with the RNP. PMID- 22090122 TI - Transmissible gastroenteritis coronavirus RNA-dependent RNA polymerase and nonstructural proteins 2, 3, and 8 are incorporated into viral particles. AB - Coronavirus replication and transcription are processes mediated by a protein complex, with the RNA-dependent RNA polymerase (RdRp) as a main component. Proteomic analysis of highly purified transmissible gastroenteritis virus showed the RdRp to be a component of the viral particles. This finding was confirmed by Western blotting, immunofluorescence, and immunoelectron microscopy analyses. Interestingly, the replicase nonstructural proteins 2, 3, and 8 colocalized with the RdRp in the viral factories and were also incorporated into the virions. PMID- 22090123 TI - Melanoma differentiation-associated gene 5 is critical for protection against Theiler's virus-induced demyelinating disease. AB - Infection of dendritic and glial cells with Theiler's murine encephalomyelitis virus (TMEV) induces various cytokines via Toll-like receptor- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways. However, the involvement and role of MDA5 in cytokine gene activation and the pathogenesis of TMEV-induced demyelinating disease are largely unknown. In this study, we demonstrate that MDA5 plays a critical role in the production of TMEV-induced alpha interferon (IFN-alpha) during early viral infection and in protection against the development of virus-induced demyelinating disease. Our results indicate that MDA5-deficient 129SvJ mice display significantly higher viral loads and apparent demyelinating lesions in the central nerve system (CNS) accompanied by clinical symptoms compared with wild-type 129SvJ mice. During acute viral infection, MDA5-deficient mice produced elevated levels of chemokines, consistent with increased cellular infiltration, but reduced levels of IFN-alpha, known to control T cell responses and cellular infiltration. Additional studies with isolated CNS glial cells from these mice suggest that cells from MDA5-deficient mice are severely compromised in the production of IFN-alpha upon viral infection, which results in increased cellular infiltration and viral loads in the CNS. Despite inadequate stimulation, the overall T cell responses to the viral determinants were significantly elevated in MDA5-deficient mice, reflecting the increased cellular infiltration. Therefore, the lack of MDA5-mediated IFN alpha production may facilitate a massive viral load and elevated cellular infiltration in the CNS during early viral infection, leading to the pathogenesis of demyelinating disease. PMID- 22090125 TI - A role for the internal repeat of the Kaposi's sarcoma-associated herpesvirus latent nuclear antigen in the persistence of an episomal viral genome. AB - The latent nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) is required for the replication and partitioning of latent viral genomes. It contains an extended internal repeat (IR) region whose function is only incompletely understood. We constructed KSHV genomes lacking either LANA (KSHV DeltaLANA) or the IR region of LANA (KSHV-LANADelta329-931). Although still capable of replicating a plasmid containing a latent origin of replication, LANADelta329-931 does not support the establishment of stable cell lines containing a KSHV genome. These findings suggest a role for the LANA IR in KSHV episomal maintenance without its being required for replication. PMID- 22090124 TI - Respiratory syncytial virus glycoprotein G interacts with DC-SIGN and L-SIGN to activate ERK1 and ERK2. AB - Respiratory syncytial virus (RSV) interaction with epithelial and dendritic cells (DCs) is known to require divalent cations, suggesting involvement of C-type lectins. RSV infection and maturation of primary human DCs are reduced in a dose dependent manner by EDTA. Therefore, we asked whether RSV infection involves DC SIGN (CD209) or its isoform L-SIGN (CD299) (DC-SIGN/R). Using surface plasmon resonance analysis, we demonstrated that the attachment G glycoprotein of RSV binds both DC- and L-SIGN. However, neutralization of DC- and L-SIGN on primary human DCs did not inhibit RSV infection, demonstrating that interactions between RSV G and DC- or L-SIGN are not required for productive infection. Thus, neither DC- nor L-SIGN represents a functional receptor for RSV. However, inhibition of these interactions increased DC activation, as evidenced by significantly higher levels of alpha interferon (IFN-alpha), MIP-1alpha, and MIP-1beta in plasmacytoid DCs (pDCs) exposed to RSV after neutralization of DC-and L-SIGN. To understand the molecular interactions involved, intracellular signaling events triggered by purified RSV G glycoprotein were examined in DC- and L-SIGN-transfected 3T3 cells. RSV G interaction with DC- or L-SIGN was shown to stimulate ERK1 and ERK2 phosphorylation, with statistically significant increases relative to mock infected cells. Neutralization of DC- and L-SIGN reduced ERK1/2 phosphorylation. With increased DC activation following DC- and L-SIGN neutralization and RSV exposure, these data demonstrate that the signaling events mediated by RSV G interactions with DC/L-SIGN are immunomodulatory and diminish DC activation, which may limit induction of RSV-specific immunity. PMID- 22090126 TI - Essential C-terminal region of the baculovirus minor capsid protein VP80 binds DNA. AB - The essential Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) minor capsid protein VP80 has been recently shown to interact with the virus triggered, nuclear F-actin cytoskeleton. A role for VP80 in virus morphogenesis has been proposed in the maturation of progeny nucleocapsids and in their egress from the virogenic stroma toward the nuclear periphery by a mechanism, which also includes F-actin filaments. We performed functional mapping of VP80 demonstrating that its highly conserved C-terminal region plays a crucial role in virion morphogenesis. Protein database mining identified a putative basic helix-loop helix (bHLH) domain, a DNA-binding module typical for eukaryotic transcription factors, in the essential C-terminal region of VP80. Using a molecular modeling approach, we predicted the three-dimensional structure of this domain, revealing some unique properties. Biochemical assays proved that VP80 can form homodimers, a critical prerequisite of DNA-binding bHLH proteins. The ability of VP80 to bind DNA was subsequently confirmed by an electrophoretic mobility shift assay. We further show that AcMNPV DNA replication occurs in the absence of VP80. Immunolabeling of VP80 in baculovirus-infected cells rather points toward its involvement in nucleocapsid maturation. The competence of VP80 to interact with both F-actin and DNA provides novel insight into baculovirus morphogenesis. PMID- 22090127 TI - Reassortment and mutation of the avian influenza virus polymerase PA subunit overcome species barriers. AB - The emergence of new pandemic influenza A viruses requires overcoming barriers to cross-species transmission as viruses move from animal reservoirs into humans. This complicated process is driven by both individual gene mutations and genome reassortments. The viral polymerase complex, composed of the proteins PB1, PB2, and PA, is a major factor controlling host adaptation, and reassortment events involving polymerase gene segments occurred with past pandemic viruses. Here we investigate the ability of polymerase reassortment to restore the activity of an avian influenza virus polymerase that is normally impaired in human cells. Our data show that the substitution of human-origin PA subunits into an avian influenza virus polymerase alleviates restriction in human cells and increases polymerase activity in vitro. Reassortants with 2009 pandemic H1N1 PA proteins were the most active. Mutational analyses demonstrated that the majority of the enhancing activity in human PA results from a threonine-to-serine change at residue 552. Reassortant viruses with avian polymerases and human PA subunits, or simply the T552S mutation, displayed faster replication kinetics in culture and increased pathogenicity in mice compared to those containing a wholly avian polymerase complex. Thus, the acquisition of a human PA subunit, or the signature T552S mutation, is a potential mechanism to overcome the species-specific restriction of avian polymerases and increase virus replication. Our data suggest that the human, avian, swine, and 2009 H1N1-like viruses that are currently cocirculating in pig populations set the stage for PA reassortments with the potential to generate novel viruses that could possess expanded tropism and enhanced pathogenicity. PMID- 22090128 TI - Identification of new viral genes and transcript isoforms during Epstein-Barr virus reactivation using RNA-Seq. AB - Using an enhanced RNA-Seq pipeline to analyze Epstein-Barr virus (EBV) transcriptomes, we investigated viral and cellular gene expression in the Akata cell line following B-cell-receptor-mediated reactivation. Robust induction of EBV gene expression was observed, with most viral genes induced >200-fold and with EBV transcripts accounting for 7% of all mapped reads within the cell. After induction, hundreds of candidate splicing events were detected using the junction mapper TopHat, including a novel nonproductive splicing event at the gp350/gp220 locus and several alternative splicing events at the LMP2 locus. A more detailed analysis of lytic LMP2 transcripts showed an overall lack of the prototypical type III latency splicing events. Analysis of nuclear versus cytoplasmic RNA-Seq data showed that the lytic forms of LMP2, EBNA-2, EBNA-LP, and EBNA-3A, -3B, and 3C have higher nuclear-to-cytoplasmic accumulation ratios than most lytic genes, including classic late genes. These data raise the possibility that at least some lytic transcripts derived from these latency gene loci may have unique, noncoding nuclear functions during reactivation. Our analysis also identified two previously unknown genes, BCLT1 and BCRT2, that map to the BamHI C-region of the EBV genome. Pathway analysis of cellular gene expression changes following B-cell receptor activation identified an inflammatory response as the top predicted function and ILK and TREM1 as the top predicted canonical pathways. PMID- 22090129 TI - Enhanced growth of influenza vaccine seed viruses in vero cells mediated by broadening the optimal pH range for virus membrane fusion. AB - Vaccination is one of the most effective preventive measures to combat influenza. Prospectively, cell culture-based influenza vaccines play an important role for robust vaccine production in both normal settings and urgent situations, such as during the 2009 pandemic. African green monkey Vero cells are recommended by the World Health Organization as a safe substrate for influenza vaccine production for human use. However, the growth of influenza vaccine seed viruses is occasionally suboptimal in Vero cells, which places limitations on their usefulness for enhanced vaccine production. Here, we present a strategy for the development of vaccine seed viruses with enhanced growth in Vero cells by changing an amino acid residue in the stem region of the HA2 subunit of the hemagglutinin (HA) molecule. This mutation optimized the pH for HA-mediated membrane fusion in Vero cells and enhanced virus growth 100 to 1,000 times in the cell line, providing a promising strategy for cell culture-based influenza vaccines. PMID- 22090130 TI - Genetic informational RNA is not required for recombinant prion infectivity. AB - Whether a genetic informational nucleic acid is required for the infectivity of transmissible spongiform encephalopathies is central to the debate about the infectious agent. Here we report that an infectious prion formed with bacterially expressed recombinant prion protein plus synthetic polyriboadenylic acid and synthetic phospholipid 1-palmitoyl-2-oleoylphosphatidylglycerol is competent to infect cultured cells and cause prion disease in wild-type mice. Our results show that genetic informational RNA is not required for recombinant prion infectivity. PMID- 22090131 TI - An overview of the vaccinia virus infectome: a survey of the proteins of the poxvirus-infected cell. AB - We have quantitatively profiled the proteins of vaccinia virus-infected HEK293T cells early and late during vaccinia virus infection. Proteins corresponding to 4,326 accessions were identified, the products of 3,798 genes. One hundred thirty six of the proteins were vaccinia virus-encoded (~64% of the known vaccinia virus proteome). The remaining accessions were from the host cell. A total of 3,403 of the 4,326 accessions could be confidently quantitated at the precursor peptide level. Although vaccinia virus gene products spanned the entire abundance dynamic range of the cellular proteome, nearly all of the proteome dynamics observed as a result of infection were manifest in the virus gene products with very little plasticity in the host cell proteome. The vaccinia virus gene products could be grouped into four kinetic classes (i.e., four combinations of pre- and postreplicative expression). These protein kinetic classes reflected, almost entirely, the corresponding gene classes within the recently characterized vaccinia virus transcriptome map. The few cellular gene products that showed notable changes in abundance upon vaccinia virus infection were concentrated largely in just a few functional groups. After all of the quantitated cellular gene products were assigned to Gene Ontology (GO)-specific groups, quantitation values for a number of these GO-specific groups were significantly skewed toward over- or underabundance with respect to the global distribution of quantitation values. Quantitative analysis of host cell functions reflected several known facets of virus infection, along with some novel observations. PMID- 22090132 TI - GRB2 interaction with the ecotropic murine leukemia virus receptor, mCAT-1, controls virus entry and is stimulated by virus binding. AB - For retroviruses such as HIV-1 and murine leukemia virus (MLV), active receptor recruitment and trafficking occur during viral entry. However, the underlying mechanisms and cellular factors involved in the process are largely uncharacterized. The viral receptor for ecotropic MLV (eMLV), a classical model for retrovirus infection mechanisms and pathogenesis, is mouse cationic amino acid transporter 1 (mCAT-1). Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein that has been shown to couple cell surface receptors, such as epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor, to intracellular signaling events. Here we examined if GRB2 could also play a role in controlling infection by retroviruses by affecting receptor function. The GRB2 RNA interference (RNAi)-mediated suppression of endogenous GRB2 resulted in a consistent and significant reduction of virus binding and membrane fusion. The binding between eMLV and cells promoted increased GRB2-mCAT-1 interactions, as detected by immunoprecipitation. Consistently, the increased colocalization of GRB2 and mCAT-1 signals was detected by confocal microscopy. This association was time dependent and paralleled the kinetics of cell-virus membrane fusion. Interestingly, unlike the canonical binding pattern seen for GRB2 and growth factor receptors, GRB2-mCAT-1 binding does not depend on the GRB2-SH2 domain mediated recognition of tyrosine phosphorylation on the receptor. The inhibition of endogenous GRB2 led to a reduction in surface levels of mCAT-1, which was detected by immunoprecipitation and by a direct binding assay using a recombinant MLV envelope protein receptor binding domain (RBD). Consistent with this observation, the expression of a dominant negative GRB2 mutant (R86K) resulted in the sequestration of mCAT-1 from the cell surface into intracellular vesicles. Taken together, these findings suggest a novel role for GRB2 in ecotropic MLV entry and infection by facilitating mCAT-1 trafficking. PMID- 22090133 TI - The highly conserved arginine residues at positions 76 through 78 of influenza A virus matrix protein M1 play an important role in viral replication by affecting the intracellular localization of M1. AB - Influenza A virus matrix protein (M1) plays an important role in virus assembly and budding. Besides a well-characterized basic amino acid-rich nuclear localization signal region at positions 101 to 105, M1 contains another basic amino acid stretch at positions 76-78 that is highly conserved among influenza A and B viruses, suggesting the importance of this stretch. To understand the role of these residues in virus replication, we mutated them to either lysine (K), alanine (A), or aspartic acid (D). We could generate viruses possessing either single or combination substitutions with K or single substitution with A at any of these positions, but not those with double substitutions with A or a single substitution with D. Viruses with the single substitution with A exhibited slower growth and had lower nucleoprotein/M1 quantitative ratio in virions compared to the wild-type virus. In cells infected with a virus possessing the single substitution with A at position 77 or 78 (R77A or R78A, respectively), the mutated M1 localized in patches at the cell periphery where nucleoprotein and hemagglutinin colocalized more often than the wild-type did. Transmission electron microscopy showed that virus possessing M1 R77A or R78A, but not the wild-type virus, was present in vesicular structures, indicating a defect in virus assembly and/or budding. The M1 mutations that did not support virus generation exhibited an aberrant M1 intracellular localization and affected protein incorporation into virus-like particles. These results indicate that the basic amino acid stretch of M1 plays a critical role in influenza virus replication. PMID- 22090134 TI - Xpr1 is an atypical G-protein-coupled receptor that mediates xenotropic and polytropic murine retrovirus neurotoxicity. AB - Xenotropic murine leukemia virus-related virus (XMRV) was first identified in human prostate cancer tissue and was later found in a high percentage of humans with chronic fatigue syndrome (CFS). While exploring potential disease mechanisms, we found that XMRV infection induced apoptosis in SY5Y human neuroblastoma cells, suggesting a mechanism for the neuromuscular pathology seen in CFS. Several lines of evidence show that the cell entry receptor for XMRV, Xpr1, mediates this effect, and chemical cross-linking studies show that Xpr1 is associated with the Gbeta subunit of the G-protein heterotrimer. The activation of adenylate cyclase rescued the cells from XMRV toxicity, indicating that toxicity resulted from reduced G-protein-mediated cyclic AMP (cAMP) signaling. Some proteins with similarity to Xpr1 are involved in phosphate uptake into cells, but we found no role of Xpr1 in phosphate uptake or its regulation. Our results indicate that Xpr1 is a novel, atypical G-protein-coupled receptor (GPCR) and that xenotropic or polytropic retrovirus binding can disrupt the cAMP mediated signaling function of Xpr1, leading to the apoptosis of infected cells. We show that this pathway is also responsible for the classic toxicity of the polytropic mink cell focus-forming (MCF) retrovirus in mink cells. Although it now seems clear that the detection of XMRV in humans was the result of sample contamination with a recombinant mouse virus, our findings may have relevance to neurologic disease induced by MCF retroviruses in mice. PMID- 22090135 TI - The cellular antiviral restriction factor tetherin does not inhibit poxviral replication. AB - Interferon-stimulated genes fulfill innate antiviral effector functions. Among them, tetherin (THN) blocks the release of many enveloped viruses from infected cells. Vaccinia virus (VACV) encodes immune modulators interfering with antiviral host responses. Therefore, it was tempting to study a potential VACV-THN interaction. Remarkably, THN expression did not inhibit VACV release and replication. VACV infection did not diminish THN surface levels or impair its function on retroviral release. This suggests that THN is unable to restrict VACV replication. PMID- 22090136 TI - Cholesterol-rich microdomains as docking platforms for respiratory syncytial virus in normal human bronchial epithelial cells. AB - Respiratory syncytial virus (RSV) is one of the major causes of respiratory infections in children, and it is the main pathogen causing bronchiolitis in infants. The binding and entry mechanism by which RSV infects respiratory epithelial cells has not yet been determined. In this study, the earliest stages of RSV infection in normal human bronchial epithelial cells were probed by tracking virions with fluorescent lipophilic dyes in their membranes. Virions colocalized with cholesterol-containing plasma membrane microdomains, identified by their ability to bind cholera toxin subunit B. Consistent with an important role for cholesterol in RSV infection, cholesterol depletion profoundly inhibited RSV infection, while cholesterol repletion reversed this inhibition. Merger of the outer leaflets of the viral envelope and the cell membrane appeared to be triggered at these sites. Using small-molecule inhibitors, RSV infection was found to be sensitive to Pak1 inhibition, suggesting the requirement of a subsequent step of cytoskeletal reorganization that could involve plasma membrane rearrangements or endocytosis. It appears that RSV entry depends on its ability to dock to cholesterol-rich microdomains (lipid rafts) in the plasma membrane where hemifusion events begin, assisted by a Pak1-dependent process. PMID- 22090137 TI - The V protein of mumps virus plays a critical role in pathogenesis. AB - Mumps virus (MuV) causes an acute infection in humans characterized by a wide array of symptoms ranging from relatively mild manifestations, such as parotitis, to more-severe complications, such as meningitis and encephalitis. Widespread mumps vaccination has reduced mumps incidence dramatically; however, outbreaks still occur in vaccinated populations. The V protein of MuV, when expressed in cell culture, blocks interferon (IFN) expression and signaling and interleukin-6 (IL-6) signaling. In this work, we generated a recombinant MuV incapable of expressing the V protein (rMuVDeltaV). The rescued MuV was derived from a clinical wild-type isolate from a recent outbreak in the United States (MuV(Iowa/US/06), G genotype). Analysis of the virus confirmed the roles of V protein in blocking IFN expression and signaling and IL-6 signaling. We also found that the rMuV(Iowa/US/06)DeltaV virus induced high levels of IL-6 expression in vitro, suggesting that V plays a role in reducing IL-6 expression. In vivo, the rMuV(Iowa/US/06)DeltaV virus was highly attenuated, indicating that the V protein plays an essential role in viral virulence. PMID- 22090139 TI - Disassembly of simian virus 40 during passage through the endoplasmic reticulum and in the cytoplasm. AB - The nonenveloped polyomavirus simian virus 40 (SV40) is taken up into cells by a caveola-mediated endocytic process that delivers the virus to the endoplasmic reticulum (ER). Within the ER lumen, the capsid undergoes partial disassembly, which exposes its internal capsid proteins VP2 and VP3 to immunostaining with antibodies. We demonstrate here that the SV40 genome does not become accessible to detection while the virus is in the ER. Instead, the genome becomes accessible two distinct detection procedures, one using anti-bromodeoxyuridine antibodies and the other using a 5-ethynyl-2-deoxyuridine-based chemical reaction, only after the emergence of partially disassembled SV40 particles in the cytoplasm. These cytoplasmic particles retain some of the SV40 capsid proteins, VP1, VP2, and VP3, in addition to the viral genome. Thus, SV40 particles undergo discrete disassembly steps during entry that are separated temporally and topologically. First, a partial disassembly of the particles occurs in the ER, which exposes internal capsid proteins VP2 and VP3. Then, in the cytoplasm, disassembly progresses further to also make the genomic DNA accessible to immune detection. PMID- 22090138 TI - Distinct domains in ORF52 tegument protein mediate essential functions in murine gammaherpesvirus 68 virion tegumentation and secondary envelopment. AB - Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus are etiologically associated with several types of human malignancies. However, as these two human gammaherpesviruses do not replicate efficiently in cultured cells, the morphogenesis of gammaherpesvirus virions is poorly understood. Murine gammaherpesvirus 68 (MHV-68) provides a tractable model to define common, conserved features of gammaherpesvirus biology. ORF52 of MHV-68 is conserved among gammaherpesviruses. We have previously shown that this tegument protein is essential for the envelopment and egress of viral particles and solved the crystal structure of ORF52 dimers. To more closely examine its role in virion maturation, we performed immunoelectron microscopy of MHV-68-infected cells and found that ORF52 localized to both mature, extracellular virions and immature viral particles in the cytoplasm. ORF52 consists of three alpha-helices followed by one beta-strand. To understand the structural requirements for ORF52 function, we constructed mutants of ORF52 and examined their ability to complement an ORF52 null MHV-68 virus. Mutations in conserved residues in the N-terminal alpha1-helix and C terminus, or deletion of the alpha2-helix, resulted in a loss-of-function phenotype. Furthermore, the alpha1-helix was crucial for the predominantly punctate cytoplasmic localization of ORF52, while the alpha2-helix was a key domain for ORF52 dimerization. Immunoprecipitation experiments demonstrated that ORF52 interacts with another MHV-68 tegument protein, ORF42; however, a single point mutation in R95 in the C terminus of ORF52 led to the loss of this interaction. Moreover, the homologues of MHV-68 ORF52 in Kaposi's sarcoma associated herpesvirus and Epstein-Barr virus complement the defect in ORF52-null MHV-68 and interact with MHV-68 ORF52. Taken together, these data uncover the relationship between the alpha-helical structure and the molecular basis for ORF52 function. This is the first structure-based functional domain mapping study for an essential gammaherpesvirus tegument protein. PMID- 22090140 TI - Epigenetic regulation of the latency-associated region of Marek's disease virus in tumor-derived T-cell lines and primary lymphoma. AB - Meq is the major Marek's disease virus (MDV)-encoded oncoprotein and is essential for T-cell lymphomagenesis. Meq and several noncoding RNAs, including three microRNA (MiR) clusters, are expressed from the repeats of the MDV genome during latent infection of T cells. To investigate the state of the chromatin in this and flanking regions, we carried out chromatin immunoprecipitation (ChIP) analysis of covalent histone modifications and associated bound proteins. T-cell lines and a lymphoma were compared. The chromatin around the promoters for Meq and the noncoding RNAs in both cell lines and the lymphoma were associated with H3K9 acetylation and H3K4 trimethylation, which are marks of transcriptionally active chromatin. These correlated with bound Meq-c-Jun heterodimers. The only binding site for Meq homodimers is located at the lytic origin of replication (OriLyt), next to the lytic gene pp38. This region lacked active marks and was associated with repressive histone modifications (H3K27 and H3K9 trimethylation). DNA CpG methylation was investigated using methylated DNA precipitation (MeDP). In cell lines, DNA methylation was abundant across the repeats but noticeably reduced or absent around the active promoters. In primary tumors, CpG methylation occurred less than 2 months after infection, focused within the ICP4 gene. These data suggest that nonrandom de novo DNA methylation occurs early in lymphomagenesis. In addition, the histone data indicate a role for Meq in the epigenetic regulation of the MDV genome repeats in transformed T cells and suggest that the OriLyt region and the Meq/MiR region might be separated by chromatin boundary elements, and preliminary data on CTCF binding are consistent with this. PMID- 22090141 TI - Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome. AB - The ability of Epstein-Barr virus (EBV) to establish latency allows it to evade the immune system and to persist for the lifetime of its host; one distinguishing characteristic is the lack of transcription of the majority of viral genes. Entry into the lytic cycle is coordinated by the viral transcription factor, Zta (BZLF1, ZEBRA, and EB1), and downstream effectors, while viral genome replication requires the concerted action of Zta and six other viral proteins at the origins of lytic replication. We explored the chromatin context at key EBV lytic cycle promoters (BZLF1, BRLF1, BMRF1, and BALF5) and the origins of lytic replication during latency and lytic replication. We show that a repressive heterochromatin like environment (trimethylation of histone H3 at lysine 9 [H3K9me3] and lysine 27 [H3K27me3]), which blocks the interaction of some transcription factors with DNA, encompasses the key early lytic regulatory regions. Epigenetic silencing of the EBV genome is also imposed by DNA methylation during latency. The chromatin environment changes during the lytic cycle with activation of histones H3, H4, and H2AX occurring at both the origins of replication and at the key lytic regulatory elements. We propose that Zta is able to reverse the effects of latency-associated repressive chromatin at EBV early lytic promoters by interacting with Zta response elements within the H3K9me3-associated chromatin and demonstrate that these interactions occur in vivo. Since the interaction of Zta with DNA is not inhibited by DNA methylation, it is clear that Zta uses two routes to overcome epigenetic silencing of its genome. PMID- 22090142 TI - Codelivery of the chemokine CCL3 by an adenovirus-based vaccine improves protection from retrovirus infection. AB - Processing and presentation of vaccine antigens by professional antigen presenting cells (APCs) is of great importance for the efficient induction of protective immunity. We analyzed whether the efficacy of an adenovirus-based retroviral vaccine can be enhanced by coadministration of adenovirus-encoded chemokines that attract and stimulate APCs. In the Friend retrovirus (FV) mouse model we coexpressed CCL3, CCL20, CCL21, or CXCL14 from adenoviral vectors, together with FV Gag and Env antigens, and then analyzed immune responses and protection from pathogenic FV infection. Although most tested chemokines did not improve protection against FV challenge, mice that received adenoviral vectors encoding CCL3 together with FV antigens showed significantly better control over viral loads and FV-induced disease than mice immunized with the viral antigens only. Improved protection correlated with enhanced virus-specific CD4+ T cell responses and higher neutralizing antibody titers. To apply these results to an HIV vaccine, mice were immunized with adenoviral vectors encoding the HIV antigens Env and Gag-Pol and coadministered vectors encoding CCL3. Again, this combination vaccine induced higher virus-specific antibody titers and CD4+ T cell responses than did the HIV antigens alone. These results indicate that coexpression of the chemokine CCL3 by adenovirus-based vectors may be a promising tool to improve antiretroviral vaccination strategies. PMID- 22090143 TI - Binding of anti-membrane-proximal gp41 monoclonal antibodies to CD4-liganded and unliganded human immunodeficiency virus type 1 and simian immunodeficiency virus virions. AB - The broadly neutralizing monoclonal antibodies (MAbs) 4E10, 2F5, and Z13e1 target membrane-proximal external region (MPER) epitopes of HIV-1 gp41 in a manner that remains controversial. The requirements for initial lipid bilayer binding and/or CD4 ligation have been proposed. To further investigate these issues, we probed for binding of these MAbs to human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) virions with protein A-conjugated gold (PAG) nanoparticles using negative-stain electron microscopy. We found moderate levels of PAG associated with unliganded HIV-1 and SIV virions incubated with the three MAbs. Significantly higher levels of PAG were associated with CD4-liganded HIV-1 (epitope-positive) but not SIV (epitope-negative) virions. A chimeric SIV virion displaying the HIV-1 4E10 epitope also showed significantly higher PAG association after CD4 ligation and incubation with 4E10. MAbs accumulated rapidly on CD4-liganded virions and slowly on unliganded virions, although both reached similar levels in time. Anti-MPER epitope-specific binding was stable to washout. Virions incubated with an irrelevant MAb or CD4-only (no MAb) showed negligible PAG association, as did a vesicle-rich fraction devoid of virions. Preincubation with Fab 4E10 inhibited both specific and nonspecific 4E10 IgG binding. Our data provide evidence for moderate association of anti-MPER MAbs to viral surfaces but not lipid vesicles, even in the absence of cognate epitopes. Significantly greater MAb interaction occurs in epitope-positive virions following long incubation or CD4 ligation. These findings are consistent with a two-stage binding model where these anti-MPER MAbs bind first to the viral lipid bilayer and then to the MPER epitopes following spontaneous or induced exposure. PMID- 22090145 TI - [Quality of life after coronary intervention or bypass surgery : SYNTAX quality of life study (synergy between PCI with taxus and cardiac surgery)]. PMID- 22090144 TI - Apoptosis induced by mammalian reovirus is beta interferon (IFN) independent and enhanced by IFN regulatory factor 3- and NF-kappaB-dependent expression of Noxa. AB - A variety of signal transduction pathways are activated in response to viral infection, which dampen viral replication and transmission. These mechanisms involve both the induction of type I interferons (IFNs), which evoke an antiviral state, and the triggering of apoptosis. Mammalian orthoreoviruses are double stranded RNA viruses that elicit apoptosis in vitro and in vivo. The transcription factors interferon regulatory factor 3 (IRF-3) and nuclear factor kappa light-chain enhancer of activated B cells (NF-kappaB) are required for the expression of IFN-beta and the efficient induction of apoptosis in reovirus infected cells. However, it is not known whether IFN-beta induction is required for apoptosis, nor have the genes induced by IRF-3 and NF-kappaB that are responsible for apoptosis been identified. To determine whether IFN-beta is required for reovirus-induced apoptosis, we used type I IFN receptor-deficient cells, IFN-specific antibodies, and recombinant IFN-beta. We found that IFN synthesis and signaling are dispensable for the apoptosis of reovirus-infected cells. These results indicate that the apoptotic response following reovirus infection is mediated directly by genes responsive to IRF-3 and NF-kappaB. Noxa is a proapoptotic BH3-domain-only protein of the Bcl-2 family that requires IRF-3 and NF-kappaB for efficient expression. We found that Noxa is strongly induced at late times (36 to 48 h) following reovirus infection in a manner dependent on IRF 3 and NF-kappaB. The level of apoptosis induced by reovirus is significantly diminished in cells lacking Noxa, indicating a key prodeath function for this molecule during reovirus infection. These results suggest that prolonged innate immune response signaling induces apoptosis by eliciting Noxa expression in reovirus-infected cells. PMID- 22090146 TI - Understanding glycomechanics using mathematical modeling: a review of current approaches to simulate cellular glycosylation reaction networks. AB - Following the footsteps of genomics and proteomics, recent years have witnessed the growth of large-scale experimental methods in the field of glycomics. In parallel, there has also been growing interest in developing Systems Biology based methods to study the glycome. The combined goals of these endeavors is to identify glycosylation-dependent mechanisms regulating human physiology, check points that can control the progression of pathophysiology, and modifications to reaction pathways that can result in more uniform biopharmaceutical processes. In these efforts, mathematical models of N- and O-linked glycosylation have emerged as paradigms for the field. While these are relatively few in number, nevertheless, the existing models provide a basic framework that can be used to develop more sophisticated analysis strategies for glycosylation in the future. The current review surveys these computational models with focus on the underlying mathematics and assumptions, and with respect to their ability to generate experimentally testable hypotheses. PMID- 22090147 TI - Hygiene hypothesis and autoimmune diseases. AB - Throughout the twentieth century, there were striking increases in the incidences of many chronic inflammatory disorders in the rich developed countries. These included autoimmune disorders such as Type 1 diabetes and multiple sclerosis. Although genetics and specific triggering mechanisms such as molecular mimicry and viruses are likely to be involved, the increases have been so rapid that any explanation that omits environmental change is incomplete. This chapter suggests that a series of environmental factors, most of them microbial, have led to a decrease in the efficiency of our immunoregulatory mechanisms because we are in a state of evolved dependence on organisms with which we co-evolved (and that had to be tolerated) as inducers of immunoregulatory circuits. These organisms ("Old Friends") are depleted from the modern urban environment. Rather than considering fetal programming by maternal microbial exposures, neonatal programming, the hygiene hypothesis, gut microbiota, and diet as separate and competing hypotheses, I attempt here to integrate these ideas under a single umbrella concept that can provide the missing immunoregulatory environmental factor that is needed to explain the recent increases in autoimmune disease. PMID- 22090148 TI - Effect of herbal preparation on heavy metal (cadmium) induced antioxidant system in female Wistar rats. AB - Cadmium is one of the elements found to damage antioxidant systems in mammals. To ameliorate cadmium toxicity and to prevent oxidative stress, natural products may be useful. In Indian ethnobotanical practice, a mixture of 17 herbal products is used to fortify the reproductive system of women after parturition and to reverse ovarian oxidative stress. Oral administration of this extract to rats exposed to cadmium was useful in reversing oxidative stress. Two different doses of cadmium (50 ppm and 200 ppm) were given to Wistar rats aged 45 and 65 days. An herbal extract derived from 17 plants was administered orally every day at a dose level of 200 mg/kg of body weight to the rats exposed to cadmium. A battery of enzymes involved in antioxidant activity in the ovary, including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione-s-transferase (GST) were measured in the control, cadmium-exposed rats without treatment and in the cadmium-exposed rats treated with herbal extract. The reduction in SOD, catalase, GPx and GST activity after cadmium exposure improved significantly in the rats treated with the herbal extract (p < 0.05). The decrease of antioxidant enzymes due to cadmium exposure was reversed significantly with herbal extract administration. The synergistic effect of each bioactive compound in different herbal extracts requires further study. PMID- 22090149 TI - Autonomic dysfunction as a delayed sequelae of acute ethylene glycol ingestion : a case report and review of the literature. AB - Ethylene glycol poisoning is a common form of poisoning worldwide. The clinical course of ethylene glycol poisoning usually follows a three-stage progression, although these stages may overlap. A fourth stage of delayed neurological dysfunction consisting of cranial neuropathies has been suggested in several case reports. We describe a patient with unique findings of postural hypotension and gastroparesis following ethylene glycol toxicity with the additional uncommon features of albuminocytologic dissociation and increased intracranial pressure with papilledema. In addition, we provide a review of the literature on delayed neurological manifestations in ethylene glycol toxicity and further elucidate a description of a fourth stage of delayed neurological dysfunction following ethylene glycol poisoning. PMID- 22090150 TI - Acamprosate modulates experimental autoimmune encephalomyelitis. AB - OBJECTIVE: This pilot study aimed to determine the efficacy of acamprosate (N acetyl homotaurine) in reducing the pathological features of experimental autoimmune encephalomyelitis (EAE) which is an animal model for multiple sclerosis (MS). BACKGROUND: The amino acid taurine has multiple biological activities including immunomodulation and neuromodulation. The synthetic acetylated taurine derivative, acamprosate, which crosses the blood-brain barrier more readily compared to taurine, is currently being used for the prevention of alcohol withdrawal symptoms associated with enhanced glutamatergic receptor function and GABA receptor hypofunction. METHODS: EAE was induced in C57BL/6 female mice with myelin oligodendrocyte glyocoprotein, amino acid 35-55. Mice were treated with 20, 100 and 500 mg/kg acamprosate for 21 days. RESULTS: Neurological scores at disease peak were reduced by 21, 64 and 9% in the 20, 100 and 500 mg/kg groups, respectively. Neurological improvement in the 100 mg/kg group correlated with a reduction in numbers of inflammatory lesions and the extent of CNS demyelination. Blood TNF-alpha levels were significantly reduced in the 500 mg/kg group. DISCUSSION: Acamprosate and other taurine analogs have a potential for future MS therapy. PMID- 22090151 TI - Associations between three characteristics of parent-youth relationships, youth substance use, and dating attitudes. AB - Various dimensions of parenting have been associated with youth risk behaviors, such as substance use and dating violence. These associations have spawned many prevention strategies that focus on parenting. However, it is unclear which characteristics of parent-youth relationships, and thus, which parent-focused prevention strategies, may be most influential in youth risk behaviors and, thus, which should be targeted in prevention. Using responses from the YouthStyles 2007 survey (N = 1,357), this study identified three youth-reported parent-youth relationship characteristics: communication about risk behaviors, closeness/respect, and rules/monitoring. The authors examined the associations among these characteristics and youths' demographics, attitudes supporting controlling dating relationships, and use of alcohol, marijuana, and tobacco. Results suggested risk behavior communication was more frequently reported by girls and was more frequent among older youth. Closeness/respect and rules/monitoring were more frequent among younger youth. Regressions suggested communication about risk behaviors was not a predictor of attitudes supporting controlling dating relationships but was a significant predictor of substance use, closeness/respect and rules/monitoring predicted substance nonuse and attitudes unsupportive of controlling dating relationships. The findings suggest that parental communication alone may not be sufficient to influence youth risk taking, but that parental monitoring and the establishment of respectful, close relationships with children may be important elements of parent-focused health promotion efforts. PMID- 22090152 TI - Successful implementation of Thai Family Matters: strategies and implications. AB - This article discusses the successful process used to assess the feasibility of implementing the Family Matters program in Bangkok, Thailand. This is important work since adopting and adapting evidence-based programs is a strategy currently endorsed by leading prevention funding sources, particularly in the United States. The original Family Matters consists of four booklets designed to increase parental communication with their adolescent children in order to delay onset of or decrease alcohol, tobacco, and other drug use. As part of the program, health educators contact parents by telephone to support them in the adoption of the program. Each booklet addresses a key aspect of strengthening families and protecting young people from unhealthy behaviors related to alcohol and other drug use. Adaptation of the program for Bangkok focused on cultural relevance and the addition of a unit targeting adolescent dating and sexual behavior. A total of 170 families entered the program, with the majority (85.3%) completing all five booklets. On average, the program took 16 weeks to complete, with families reporting high satisfaction with the program. This article provides greater detail about the implementation process and what was learned from this feasibility trial. PMID- 22090154 TI - The use of clinical broadband UV radiometers for optical radiation hazard measurements. AB - The implementation of the UK Control of Artificial Optical Radiation at Work Regulations 2010 requires the employer to perform a risk assessment of workers' exposure to UV radiation from phototherapy equipment in the hospital environment. The objective of this study was to demonstrate that, where the source spectrum is known, an assessment of exposure to UV sources commonly used in hospitals, including assessment of reflections and transmission through personal protective equipment, may be performed with sufficient reliability by radiometer measurement rather than by complex spectroradiometric measurements. An intercomparison of radiometer and spectroradiometer measurements of exposure to UV sources was carried out. Direct exposure was considered, as well as exposure to reflected or scattered beams and that transmitted through eyewear. Assessment by radiometer of direct exposure and exposure to reflections demonstrated an acceptable measurement error in the context of the inherent uncertainty in the assumptions of the exposure scenario. Assessment of transmitted beams may result in a greater measurement error due to spectral mismatch; however, for typical exposure scenarios the error remained acceptable in comparison with the exposure limit value. The methodology presented reduces the complexity of the measurement of UV hazard levels for common phototherapy equipment. PMID- 22090153 TI - Challenges and opportunities for promoting booster seat use: progressive dissemination of a high-threat message. AB - Motivating parents to take certain safety precautions when traveling with their children remains challenging for advocates. Caregivers of booster-aged children are particularly difficult to reach because they do not consider their children to be of "safety-seat" age and have inherently low perceptions of vulnerability to crash injury. Unfortunately, most booster seat programs fail to adequately motivate their intended population because they are primarily informational in nature and rely on caregivers to seek out and attend to the information. In this article, interventions using threat appeal tactics and progressive dissemination methods are recommended to effectively target participation and perceptions of vulnerability among this population. Recent research on risk communication indicates that threat appeals are supported when they contain high threat and high efficacy components. Threat appeal tactics are particularly desirable when perception of vulnerability is low, as is the case with parents of booster-aged children. In addition to theoretical arguments for more aggressive intervention approaches, a case example is presented wherein such techniques were used to promote booster seat use. The intervention resulted in significant increases in knowledge, risk-reduction attitudes, sense of efficacy, and observed booster seat use. Through use of progressive dissemination methods, the intervention has reached an audience of 431,600 people and counting. PMID- 22090155 TI - Impact of PIT tagging on recapture rates, body condition and reproductive success of wild Daubenton's bats (Myotis daubentonii). AB - A successful and safe methodology for the subcutaneous insertion of passive integrated transponder (PIT) tags in a small- to medium-sized bat (average mass 9 g) under isoflurane-induced anaesthesia is described. Passive integrated transponder (PIT) tagging had no significant impact on the rate of recapture, body condition index (BCI) (bodyweight/forearm length) and reproductive success of tagged individuals, and no visible injuries or health problems were observed in any of the recaptured bats. Tagging success, in terms of retention and function, was 92 per cent (n=61) by the third year of using the method. Sixteen per cent (n=39) of bats tagged during the three-year study period were not producing positive scans with the microchip reader when recaptured after previously successful tag insertion, indicating that the tags were either working their way out of the bats or ceasing to function. PMID- 22090156 TI - Enhancing clinical learning in the workplace: a qualitative study. AB - Workplace learning (WPL) is seen as an essential component of clinical veterinary education by the veterinary profession. This study sought to understand this type of learning experience more deeply. This was done utilising observations of students on intramural rotations (IMR) and interviews with students and clinical staff. WPL was seen as an opportunity for students to apply knowledge and develop clinical and professional skills in what is generally regarded as a safe, authentic environment. Clinical staff had clear ideas of what they expected from students in terms of interest, engagement, professionalism, and active participation, where this was appropriate. In contrast, students often did not know what to expect and sometimes felt under-prepared when entering the workplace, particularly in a new species area. With the support of staff acting as mentors, students learned to identify gaps in their knowledge and skills, which could then be addressed during specific IMR work placements. Findings such as these illustrate both the complexities of WPL and the diversity of different workplace settings encountered by the students. PMID- 22090157 TI - Dermoid sinus type IV associated with spina bifida in a young Victorian bulldog. PMID- 22090158 TI - Visual search deficits are independent of magnocellular deficits in dyslexia. AB - The aim of this study was to investigate the theory that visual magnocellular deficits seen in groups with dyslexia are linked to reading via the mechanisms of visual attention. Visual attention was measured with a serial search task and magnocellular function with a coherent motion task. A large group of children with dyslexia (n = 70) had slower serial search times than a control group of typical readers. However, the effect size was small (eta(p)(2) = 0.05) indicating considerable overlap between the groups. When the dyslexia sample was split into those with or without a magnocellular deficit, there was no difference in visual search reaction time between either group and controls. The data suggest that magnocellular sensitivity and visual spatial attention weaknesses are independent of one another. They also provide more evidence of heterogeneity in response to psychophysical tasks in groups with dyslexia. Alternative explanations for poor performance on visual attention tasks are proposed along with avenues for future research. PMID- 22090159 TI - Epinephrine: a short- and long-term regulator of stress and development of illness : a potential new role for epinephrine in stress. AB - Epinephrine (Epi), which initiates short-term responses to cope with stress, is, in part, stress-regulated via genetic control of its biosynthetic enzyme, phenylethanolamine N-methyltransferase (PNMT). In rats, immobilization (IMMO) stress activates the PNMT gene in the adrenal medulla via Egr-1 and Sp1 induction. Yet, elevated Epi induced by acute and chronic stress is associated with stress induced, chronic illnesses of cardiovascular, immune, cancerous, and behavioral etiologies. Major sources of Epi include the adrenal medulla and brainstem. Although catecholamines do not cross the blood-brain barrier, circulating Epi from the adrenal medulla may communicate with the central nervous system and stress circuitry by activating vagal nerve beta-adrenergic receptors to release norepinephrine, which could then stimulate release of the same from the nucleus tractus solitarius and locus coeruleus. In turn, the basal lateral amygdala (BLA) may activate to stimulate afferents to the hypothalamus, neocortex, hippocampus, caudate nucleus, and other brain regions sequentially. Recently, we have shown that repeated IMMO or force swim stress may evoke stress resiliency, as suggested by changes in expression and extinction of fear memory in the fear-potentiated startle paradigm. However, concomitant adrenergic changes seem stressor dependent. Present studies aim to identify stressful conditions that elicit stress resiliency versus stress sensitivity, with the goal of developing a model to investigate the potential role of Epi in stress-associated illness. If chronic Epi over expression does elicit illness, possibilities for alternative therapeutics exist through regulating stress-induced Epi expression, adrenergic receptor function and/or corticosteroid effects on Epi, adrenergic receptors and the stress axis. PMID- 22090161 TI - Sex, abortion and Obama. PMID- 22090160 TI - Correlations between cholinesterase activity and cognitive scores in post ischemic rats and patients with vascular dementia. AB - The biochemical changes such as the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were investigated in rats with global cerebral ischemia and in vascular dementia (VaD) subjects in this study. The AChE activity showed a significant decrease in plasma and a significant increase in the hippocampus but not in the cerebral cortices in the post-ischemic rats as compared to the controls. The learning abilities and spatial memory were impaired in the post-ischemic rats as compared to controls. Furthermore, the AChE activity in plasma was significantly reduced in VaD subjects as compared to normal control subjects. The BuChE activity did not show any change in both post-ischemic rats and VaD patients. Interestingly, the decreased AChE activity in plasma from the post-ischemic rats and the VaD subjects showed a significant correlation with the declined learning and memory ability, and the Mini-Mental State Examination score, respectively. These data suggest that the AChE activity is involved in the cognitive recovery after ischemia, and the plasma level of AChE might be a reliable supplementary peripheral biomarker to evaluate the cognitive recovery degree of VaD patients. PMID- 22090162 TI - Advances in intrauterine technique training. PMID- 22090163 TI - Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. AB - BACKGROUND: The pathophysiology of aortic stenosis is incompletely understood, and the relative contributions of valvular calcification and inflammation to disease progression are unknown. METHODS AND RESULTS: Patients with aortic sclerosis and mild, moderate, and severe stenosis were compared prospectively with age- and sex-matched control subjects. Aortic valve severity was determined by echocardiography. Calcification and inflammation in the aortic valve were assessed by 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake with the use of positron emission tomography. One hundred twenty-one subjects (20 controls; 20 aortic sclerosis; 25 mild, 33 moderate, and 23 severe aortic stenosis) were administered both 18F-NaF and 18F-FDG. Quantification of tracer uptake within the valve demonstrated excellent interobserver repeatability with no fixed or proportional biases and limits of agreement of +/-0.21 (18F-NaF) and +/-0.13 (18F-FDG) for maximum tissue-to-background ratios. Activity of both tracers was higher in patients with aortic stenosis than in control subjects (18F NaF: 2.87+/-0.82 versus 1.55+/-0.17; 18F-FDG: 1.58+/-0.21 versus 1.30+/-0.13; both P<0.001). 18F-NaF uptake displayed a progressive rise with valve severity (r(2)=0.540, P<0.001), with a more modest increase observed for 18F-FDG (r(2)=0.218, P<0.001). Among patients with aortic stenosis, 91% had increased 18F NaF uptake (>1.97), and 35% had increased 18F-FDG uptake (>1.63). A weak correlation between the activities of these tracers was observed (r(2)=0.174, P<0.001). CONCLUSIONS: Positron emission tomography is a novel, feasible, and repeatable approach to the evaluation of valvular calcification and inflammation in patients with aortic stenosis. The frequency and magnitude of increased tracer activity correlate with disease severity and are strongest for 18F-NaF. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01358513. PMID- 22090164 TI - Look more closely at the valve: imaging calcific aortic valve disease. PMID- 22090165 TI - Loss-of-function sodium channel mutations in infancy: a pattern unfolds. PMID- 22090166 TI - Brugada-like syndrome in infancy presenting with rapid ventricular tachycardia and intraventricular conduction delay. AB - BACKGROUND: Brugada syndrome is a potentially serious channelopathy that usually presents in adulthood and has only rarely been described in infancy. In the absence of metabolic or structural cardiac disease, rapid ventricular tachycardia (>200 bpm) and primary cardiac conduction disease are uncommon in infancy. We hypothesized that infants having rapid ventricular tachycardia and conduction abnormalities and not having structural or metabolic pathogeneses were likely to have mutations in depolarizing current channels. METHODS AND RESULTS: A retrospective review of all clinical materials from a single institution over a 9 year period from all infants <2 years old and having a discharge diagnosis of ventricular tachycardia or ventricular fibrillation was performed. Among 32 infants fulfilling inclusion criteria, 12 had a structurally normal heart, and 9 of them had either prolonged QRS duration or Brugada pattern while in sinus rhythm. Of those 5 infants not having a definitive pathogenesis, electrophysiological testing had been performed in 4, and genetic testing had been performed in all 5 of those infants. During electrophysiological testing, a prolonged HV interval was present in 2 of 4, inducible ventricular tachycardia was present in 1 of 4, and a type 1 Brugada pattern was induced by intravenous procainamide in 3 of 4. Genetic testing revealed disease-causing mutations in depolarizing sodium (SCN5A) or calcium (CaCNB2b) channels in all 5 infants. CONCLUSIONS: Infants having rapid ventricular tachycardia and conduction abnormalities in the absence of structural or metabolic abnormalities are likely to have disease-causing mutations in cardiac depolarizing channels. PMID- 22090167 TI - Colchicine reduces postoperative atrial fibrillation: results of the Colchicine for the Prevention of the Postpericardiotomy Syndrome (COPPS) atrial fibrillation substudy. AB - BACKGROUND: Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery. METHODS AND RESULTS: The COPPS POAF substudy included 336 patients (mean age, 65.7+/-12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients >=70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; P=0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4+/-3.7 versus 10.3+/-4.3 days; P=0.040) and rehabilitation stay (12.1+/-6.1 versus 13.9+/-6.5 days; P=0.009). Side effects were similar in the study groups. CONCLUSION: Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay. PMID- 22090168 TI - Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral artery disease: six-month outcomes from the claudication: exercise versus endoluminal revascularization (CLEVER) study. AB - BACKGROUND: Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). METHODS AND RESULTS: We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8+/-4.6, 3.7+/-4.9, and 1.2+/-2.6 minutes, respectively; P<0.001 for the comparison of SE versus OMC, P=0.02 for ST versus OMC, and P=0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114+/-274 versus 73+/-139 versus -6+/-109 steps per hour), but these differences were not statistically significant. CONCLUSIONS: SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1. Unique identifier: NCT00132743. PMID- 22090169 TI - Metabolic restriction of cancer cells in vitro causes karyotype contraction--an indicator of cancer promotion? AB - The metabolism of cultured cancer cells is stimulated by 21% oxygen and generous nutrition, while real tumors grow in oxygen and nutrient-restricted environments. The effect of these contrasted conditions was studied in five hyperploid (54-69) cancer cell lines. When grown under anoxia and in the presence of antioxidant metabolic restrictors, the cell lines quickly reverted to almost normal chromosome numbers (47-49). The stepped withdrawal of oxygen over K562 showed progressive increases in proliferation rate and the acquisition of a stable, stem phenotype. In genetic studies, hyperploid cancer cells adjusted their chromosome numbers up or down to match their micro-environment through rapid mechanisms of endo-reduplication or chromosome loss. These fast reactions may explain the surprising adaptability of tumor cells to oncologic interventions. Furthermore, karyotype contraction may provide a basis for the previously observed carcinogenic influence of the administration of some antioxidants in human populations. PMID- 22090170 TI - De novo sequencing and homology searching. AB - In proteomics, de novo sequencing is the process of deriving peptide sequences from tandem mass spectra without the assistance of a sequence database. Such analyses have traditionally been performed manually by human experts, and more recently by computer programs that have been developed because of the need for higher throughput. Although powerful, de novo sequencing often can only determine partially correct sequence tags because of imperfect tandem mass spectra. However, these sequence tags can then be searched in a sequence database to identify the exact or a homologous peptide. Homology searches are particularly useful for the study of organisms whose genomes have not been sequenced. This tutorial will present background important to understanding de novo sequencing, suggestions on how to do this manually, plus descriptions of computer algorithms used to automate this process and to subsequently carryout homology-based database searches. This Tutorial is part of the International Proteomics Tutorial Programme (IPTP 1). PMID- 22090172 TI - Systemic administration of LPS worsens delayed deterioration associated with vasospasm after subarachnoid hemorrhage through a myeloid cell-dependent mechanism. AB - BACKGROUND: Delayed deterioration associated with vasospasm (DDAV) after aneurismal subarachnoid hemorrhage (SAH) is a major cause of morbidity. We have previously shown that myeloid cell depletion before experimental SAH in a murine model ameliorates DDAV. In this study, we address whether systemic administration of lipopolysaccharide (LPS) worsens DDAV in a myeloid cell-dependent fashion. METHODS: We challenged mice in our experimental SAH model with LPS before hemorrhage and evaluated the degree of vasospasm on day 6 with India ink angiography; behavioral deficits by rotorod, Y-maze, and Barnes maze testing; microglial activation early after SAH by immunohistochemistry; and the brain levels of the chemokines CCL5 and KC at the time of vasospasm. Another group of animals were given the myeloid cell-depleting antibody against the neutrophil antigen Ly6G/C prior to LPS administration and SAH. RESULTS: LPS followed by SAH significantly worsens angiographic vasospasm as well as performance on the Barnes maze but not the Y-maze or rotorod tests. There was an increased activation of microglia in animals with LPS before SAH compared to SAH alone. Depletion of myeloid cells before LPS administration inhibited the development of vasospasm, improved the performance on behavioral tests, and reduced microglial activation. The chemokines CCL5 and KC were incrementally elevated in SAH and LPS SAH, but suppressed in animals with myeloid cell depletion. CONCLUSIONS: LPS administration before SAH worsens DDAV through a myeloid cell-dependent mechanism supporting studies in humans which show that systemic inflammation increases the likelihood of developing DDAV. PMID- 22090171 TI - Hyperosmolar therapy for intracranial hypertension. AB - The use of hyperosmolar agents for intracranial hypertension was introduced in the early 20th century and remains a mainstay of therapy for patients with cerebral edema. Both animal and human studies have demonstrated the efficacy of two hyperosmolar agents, mannitol and hypertonic saline, in reducing intracranial pressure via volume redistribution, plasma expansion, rheologic modifications, and anti-inflammatory effects. However, because of physician and institutional variation in therapeutic practices, lack of standardized protocols for initiation and administration of therapy, patient heterogeneity, and a paucity of randomized controlled trials have yielded little class I evidence on which clinical decisions can be based, most current evidence regarding the use of hyperosmolar therapy is derived from retrospective analyses (class III) and case series (class IV). In this review, we summarize the available evidence regarding the use of hyperosmolar therapy with mannitol or hypertonic saline for the medical management of intracranial hypertension and present a comprehensive discussion of the evidence associated with various theoretical and practical concerns related to initiation, dosage, and monitoring of therapy. PMID- 22090173 TI - The impact of low vision on activities of daily living, symptoms of depression, feelings of anxiety and social support in community-living older adults seeking vision rehabilitation services. AB - PURPOSE: Previous studies showed that older persons with vision loss generally reported low levels of health-related quality of life, although study outcomes with respect to feelings of anxiety and social support were inconsistent. The objective of this study was to examine the impact of low vision on health-related quality of life, including feelings of anxiety and social support, among community-living older adults seeking vision rehabilitation services. METHODS: Differences of activities of daily living (Groningen Activity Restriction Scale GARS), symptoms of depression and feelings of anxiety (Hospital Anxiety and Depression Scales-HADS) and social support (Social Support Scale Interactions SSL12-I) between 148 older persons >=57 years with low vision and a reference population (N = 4,792) including eight patient groups with different chronic conditions were tested with Student's t tests. RESULTS: Older persons with vision loss reported poorer levels of functioning with respect to activities of daily living, symptoms of depression and feelings of anxiety as compared to the general older population as well as compared to older patients with different chronic conditions. In contrast, older persons with vision loss reported higher levels of social support. CONCLUSIONS: Vision loss has a substantial impact on activities of daily living, symptoms of depression and feelings of anxiety. Professionals working at vision rehabilitation services may improve their quality of care as they take such information into account in their intervention work. PMID- 22090175 TI - "Aspirin - resistance"? A few critical considerations on definition, terminology, diagnosis, clinical value, natural course of atherosclerotic disease, and therapeutic consequences. AB - Based upon various platelet function tests and the fact that patients experience vascular events despite taking acetylsalicylic acid (ASA or aspirin), it has been suggested that patients may become resistant to the action of this pharmacological compound. However, the term "aspirin resistance" was created almost two decades ago but is still not defined. Platelet function tests are not standardized, providing conflicting information and cut-off values are arbitrarily set. Interest comparison reveals low agreement. Even point of care tests have been introduced before appropriate validation. Inflammation may activate platelets, co-medication(s) may interfere significantly with aspirin action on platelets. Platelet function and Cox-inhibition are only some of the effects of aspirin on haemostatic regulation. One single test is not reliable to identify an altered response. Therefore, it may be more appropriate to speak about "treatment failure" to aspirin therapy than using the term "aspirin resistance". There is no evidence based justification from either the laboratory or the clinical point of view for platelet function testing in patients taking aspirin as well as from an economic standpoint. Until evidence based data from controlled studies will be available the term "aspirin resistance" should not be further used. A more robust monitoring of factors resulting in cardiovascular events such as inflammation is recommended. PMID- 22090174 TI - Vaccines and immunomodulatory therapies for food allergy. AB - The apparent increase in food allergy prevalence has led to a surge in the amount of clinical and basic science research dedicated to the field. At the current time, allergen avoidance remains the cornerstone of treatment; however, recent clinical trials investigating various forms of immunotherapy have opened doors to the possible future application of an active treatment strategy in everyday practice. In addition, improvements in molecular biology have allowed researchers to purify, clone, and modify allergens, thus laying the groundwork for research on vaccines using modified proteins of decreased allergenicity. Finally, various allergen-nonspecific immunomodulatory therapies are also being investigated as a means to alter the immune response to food allergens. With these emerging therapeutic strategies, it is hoped that practitioners will have options in caring for their food-allergic patients in the near future. PMID- 22090176 TI - Vascular anomalies in children. AB - Vascular anomalies are divided in two major categories: tumours (such as infantile hemangiomas) and malformations. Hemangiomas are common benign neoplasms that undergo a proliferative phase followed by stabilization and eventual spontaneous involution, whereas vascular malformations are rare structural anomalies representing morphogenetic errors of developing blood vessels and lymphatics. It is important to properly diagnose vascular anomalies early in childhood because of their distinct differences in morbidity, prognosis and need for a multidisciplinary management. We discuss a number of characteristic clinical features as clues for early diagnosis and identification of associated syndromes. PMID- 22090177 TI - Intramural delivery of bortezomib inhibits restenosis following arterial injury. AB - BACKGROUND: Several studies have demonstrated that the proteasome inhibitors prevent restenosis following arterial injury. The proteasome inhibitor bortezomib shows anti-inflammatory and antiproliferative effects. Here, we evaluate the efficacy of bortezomib in inhibiting the restenosis following arterial injury and the effect on nuclear factor kappa B (NF-kappaB) and p27. METHODS: An injured iliac artery rabbit model was established by balloon over-stretching. Rabbits were intramurally infused with bortezomib or normal saline by a transport coronary dilatation catheter in the bortezomib (n = 20) or control (n = 20) groups, respectively, and they were sacrificed on the 7th or 21th day following the arterial injury. Neointimal area was measured by computer analysis of photomicrographs, while expression of NF-kappaB and of p27 on day 7 were evaluated by Western blotting and immunohistochemistry, respectively. RESULTS: Expression of p27 (56.10 +/- 3.03% vs. 10.24 +/- 0.60%, p < 0.05) was significantly higher while that of NF-kappaB (0.44 +/- 0.02 vs. 0.70 +/- 0.03, p < 0.05) was significantly lower in the bortezomib group than in control group on day 7 after arterial injury. Neointimal formation was significantly lower in the bortezomib group on day 21 after arterial injury (0.67 +/- 0.03 vs. 1.30 +/- 0.05 intima/media ratio, p < 0.05). CONCLUSIONS: Intramural delivery of bortezomib reduces neointimal formation, possibly via a mechanism involving upregulation of the p27 and downregulation of the NF-kappaB. Bortezomib therefore may be an alternative therapeutic approach for preventing restenosis. PMID- 22090178 TI - Patient specific biomodel of the whole aorta - the importance of calcified plaque removal. AB - BACKGROUND: The use of anatomical models produced by 3D printing technique (rapid prototyping, RP) is gaining increased acceptance as a complementary tool for planning complex surgical interventions. This paper describes a method for creating a patient specific replica of the whole aorta. METHODS: Computed tomography angiography (CTA) DICOM-data was converted to a three-dimensional computer aided design-model (CAD) of the inner wall of the aorta representing the lumen where the calcified plaque contribution was removed in a multi-step editing manoeuvre. The edited CAD-model was used for creating a physical plaster model of the true lumen in a 3D-printer. Elastic and transparent silicon was applied onto the plaster model, which was then removed leaving a silicon replica of the aorta. RESULTS: The median (interquartile range) difference between diameters obtained from CTA- and RP plaster-model at 19 predefined locations was 0.5 mm (1 mm) which corresponds to a relative median difference of 4.6% (7.0%). The average wall thickness of the silicone model was 3.5 mm. The elasticity property and performance during intervention was good with an acceptable transparency. CONCLUSIONS: The integration of RP-techniques with CAD based reconstruction of 3D medical imaging data provides the needed tools for making a truly patient specific replica of the whole aorta with high accuracy. Plaque removal postprocessing is necessary to obtain a true inner wall configuration. PMID- 22090179 TI - Results of combined preoperative direct percutaneous embolization and surgical excision in treatment of carotid body tumors. AB - BACKGROUND: Carotid body tumors are infrequent neoplasms in daily practice. Diagnostic difficulties exist because of their slow growth and asymptomatic progress. The surgical treatment is complicated and difficult due to their proximity to vascular and neural structures. In this study we present the results of 12 patients operated for carotid body tumor that underwent preoperative percutaneous direct embolization. PATIENTS AND METHODS: The data of 12 patients, diagnosed with carotid body tumor and surgically treated at our department between 2000 and 2010, was retrospectively analyzed. Duplex ultrasound, computerized tomography and selective carotid angiography were the applied diagnostic tools. Two days before the planned surgery all patients underwent percutaneous direct embolization to achieve devascularization of the tumor. Afterwards, surgical excision of the mass under general anesthesia was performed in all cases. RESULTS: Five tumors were classified as Shamblin type I (41.7%), and the others were type II (58.3%). All masses were removed sub-adventitially and no vascular reconstruction was necessary. There was no mortality and no permanent neural damage. Malfunction of the tongue was observed in only one case, which recovered completely in one month. There was one recurrence detected by Duplex ultrasound and angiography during the follow up period. CONCLUSIONS: Surgical excision is mandatory to be performed as soon as diagnosed in carotid body tumors. Preoperative direct percutaneous embolization of the mass helps to devascurize the tumor, enabling an optimal surgical procedure. The outcomes of such a combined intervention are excellent and neurovascular structure preservation decreases complication and morbidity rates. PMID- 22090180 TI - The concept of an anatomy related individual arterial access: lowering technical and clinical complications with transradial access in bovine- and type-III aortic arch carotid artery stenting. AB - BACKGROUND: Carotid artery stenting (CAS) from the femoral approach can be anatomically very difficult and the incidence of complications is higher in patients with anatomical variations of the aortic arch, difficulties related to peripheral vascular disease and/or with access site complications. Because the typical morphology in patients with a bovine- or type-III aortic arch applies for an arterial access from the right upper extremity (e.g. radial, brachial) we evaluated success rates and safety of the right transradial access in a prospective study. PATIENTS AND METHODS: Between June 2009 and October 2010, seventeen patients (mean age 74,4 +/- 9 years, 10 male) with a bovine- (n = 4) or type-III aortic arch (n = 12) underwent CAS with a planned transradial- (n = 3) or after problematic transfemoral access (n = 14). In patients with a type-III aortic arch (n = 13), the right target common carotid artery (CCA) was cannulated from the right radial artery with a 5F IMA diagnostic catheter-, in patients with a bovine aortic arch (n = 4), the left CCA was accessed from the right radial artery with a 5F Amplatz- or Judkins left catheter. In all patients a 6F- (n = 14) or 5F- (n = 3) shuttle sheath was inserted via the diagnostic catheter and a 0.035? extra-stiff guidewire. All interventions were carried out with the use of a peripheral embolization protection device (EPD). Primary study endpoints were procedural success and major adverse cardiac and cerebrovascular events (MACCE), secondary endpoints were access site complications and the mean intervention time. RESULTS: Procedural success could be achieved in all patients (100 %), MACCE and access site complications did not occur in any patient. Mean interventional time was 48 +/- 18 min. CONCLUSIONS: CAS using the right transradial approach for left CAS in bovine-type aortic arch or the right transradial approach in type-III aortic arch for right CAS appears to be safe and technically feasible. PMID- 22090181 TI - Surgical reconstruction for unilateral iliac artery lesions in patients younger than 50 years. AB - BACKGROUND: To evaluate safety, short and long-term graft patency, clinical success rates, and factors associated with patency, limb salvage and mortality after surgical reconstruction in patients younger than 50 years of age who had undergone unilateral iliac artery bypass surgery. PATIENTS AND METHODS: From January 2000 to January 2010, 65 consecutive reconstructive vascular operations were performed in 22 women and 43 men of age < 50 years with unilateral iliac atherosclerotic lesions and claudication or chronic limb ischemia. All patients were followed at 1, 3, 6, and 12 months after surgery and every 6 months thereafter. RESULTS: There was in-hospital vascular graft thrombosis in four (6.1 %) patients. No in-hospital deaths occurred. Median follow-up was 49.6 +/- 33 months. Primary patency rates at 1-, 3-, 5-, and 10-year were 92.2 %, 85.6 %, 73.6 %, and 56.5 %, respectively. Seven patients passed away during follow-up of which four patients due to coronary artery disease, two patients due to cerebrovascular disease and one patient due to malignancy. Limb salvage rate after 1-, 3-, 5-, and 10-year follow-up was 100 %, 100 %, 96.3 %, and 91.2 %, respectively. Cox regression analysis including age, sex, risk factors for vascular disease, indication for treatment, preoperative ABI, lesion length, graft diameter and type of pre-procedural lesion (stenosis/occlusion), showed that only age (beta - 0.281, expected beta 0.755, p = 0.007) and presence of diabetes mellitus during index surgery (beta - 1.292, expected beta 0.275, p = 0.026) were found to be significant predictors of diminishing graft patency during the follow-up. Presence of diabetes mellitus during index surgery (beta - 1.246, expected beta 0.291, p = 0.034) was the only variable predicting mortality. CONCLUSIONS: Surgical treatment for unilateral iliac lesions in patients with premature atherosclerosis is a safe procedure with a low operative risk and acceptable long-term results. Diabetes mellitus and age at index surgery are predictive for low graft patency. Presence of diabetes is associated with decreased long-term survival. PMID- 22090182 TI - Percutaneous transluminal angioplasty versus primary stenting in infrapopliteal arteries in critical limb ischemia. AB - BACKGROUND: In endovascular recanalisation of infrapopliteal arteries, studies have already pointed out the value of balloon angioplasty, but for stent implantation very few randomized controlled data exist so far. PATIENTS AND METHODS: We conducted a randomized controlled prospective trial in patients with critical limb ischemia (CLI) comparing the effect of percutaneous transluminal balloon angioplasty (PTA) versus primary stenting in infrapopliteal arteries, concerning 1-year clinical benefit and reobstruction rate. RESULTS: 54 patients were either randomized for primary stenting (balloon expandable stent) or PTA alone, 33 patients were assigned to the PTA group, 21 patients to the stent group. The whole follow up period of 12 months was completed by 46 patients. Improvement by at least one Rutherford classification was reached by a total of 33 (75.0 %) of patients at month 12, 22 (81.5 %) in the PTA group and 11 (64.7 %) in the stent group. A complete ulcer healing at month 12 showed 21 (63.6 %) of all patients, with a higher percentage in patients treated with PTA alone 16 (80.0 %) vs 5 (38.5 %). 50.0 % of all patients showed re-obstruction over the follow-up period, 39.4 % of the PTA and 66.7 % of the stent group. At month 3 primary patency rate was nearly equal in both groups (76.7 % PTA vs 75.0 % stent), but drifted apart with the duration of the follow-up period, with a primary patency at month 12 in the PTA group of 48,1 % vs 35,3 % in the stent group. As for secondary patency at month 12 the PTA group showed a patency rate of 70.4 %, vs 52.9 % in the stent group. CONCLUSIONS: Primary stenting with balloon expandable stents in the infrapopliteal arteries does not outway the benefit of PTA alone with the application of modern hydrophilic balloon catheters in patients with CLI. PMID- 22090183 TI - Pseudoaneurysm of the left internal carotid artery following tonsillectomy. AB - Internal carotid artery pseudoaneurysm is a rare complication of deep neck infections. The authors report the case of a 17-year-old male who presented to the Department of Otorhinolaryngology with an acute tonsillitis requiring tonsillectomy. Four weeks after the surgery the patient was readmitted because of progressive swallowing, trismus, and worsening headache. Computed tomography revealed a pseudoaneurysm of the left internal carotid artery in the extracranial segment. A bare Wallstent was implanted primarily and a complete occlusion of the pseudoaneurysm was achieved. The endovascular approach is a quick and safe method for the treatment of a pseudoaneurysm of the internal carotid artery. PMID- 22090184 TI - Synchronous celiac axis and superior mesenteric artery embolism. AB - We present a case of combined celiac axis and superior mesenteric artery embolism in a 70-year-old patient that was examined in emergency department for atrial fibrillation and diffuse abdominal pain. Standard abdominal x-ray showed air in the portal vein. CT scan with contrast showed air in the lumen of the stomach and small intestine, bowel distension with wall thickening, and a free gallstone in the abdominal cavity. Massive embolism of both celiac axis and superior mesenteric artery was seen after contrast administration. On laparotomy, complete necrosis of the liver, spleen, stomach and small intestine was found. Gallbladder was gangrenous and perforated, and the gallstone had migrated into the abdominal cavity. We found free air that crackled on palpation of the veins of the gastric surface. The patient,s condition was incurable and she died of multiple organ failure a few hours after surgery. Acute visceral thromboembolism should always be excluded first if a combination of atrial fibrillation and abdominal pain exists. Determining the serum levels of d-dimers and lactate, combined with CT scan with contrast administration can, in most cases, confirm the diagnosis and lead to faster surgical intervention. It is crucial to act early on clinical suspicion and not to wait for the development of hard evidence. PMID- 22090187 TI - Spatial mislocalization as a consequence of sequential coding of stimuli. AB - In three experiments, we tested whether sequentially coding two visual stimuli can create a spatial misperception of a visual moving stimulus. In Experiment 1, we showed that a spatial misperception, the flash-lag effect, is accompanied by a similar temporal misperception of first perceiving the flash and only then a change of the moving stimulus, when in fact the two events were exactly simultaneous. In Experiment 2, we demonstrated that when the spatial misperception of a flash-lag effect is absent, the temporal misperception is also absent. In Experiment 3, we extended these findings and showed that if the stimulus conditions require coding first a flash and subsequently a nearby moving stimulus, a spatial flash-lag effect is found, with the position of the moving stimulus being misperceived as shifted in the direction of its motion, whereas this spatial misperception is reversed so that the moving stimulus is misperceived as shifted in a direction opposite to its motion when the conditions require coding first the moving stimulus and then the flash. Together, the results demonstrate that sequential coding of two stimuli can lead to a spatial misperception whose direction can be predicted from the order of coding the moving object versus the flash. We propose an attentional sequential-coding explanation for the flash-lag effect and discuss its explanatory power with respect to related illusions (e.g., the Frohlich effect) and other explanations. PMID- 22090186 TI - Maternal and child expressed emotion as predictors of treatment response in pediatric obsessive-compulsive disorder. AB - Expressed emotion (EE) is associated with symptoms and treatment outcome in various disorders. Few studies have examined EE in pediatric OCD and none of these has assessed the child's perspective. This study examined the relationship among maternal and child EE, child OCD severity, and OCD-related functioning pre- and post-treatment. At pre-treatment, mothers completed speech samples about the child with OCD and an unaffected sibling. Children with OCD completed speech samples about parents. There were low rates of high maternal EE (child with OCD: 16.1%; sibling: 2.6%) and high child EE about parents (mothers: 11.9%; fathers: 10.2%). High EE was primarily characterized by high criticism, not high overinvolvement. High maternal EE and child EE regarding fathers were associated with pre-treatment child OCD severity but not post-treatment severity. High child and maternal EE were predictive of post-treatment OCD-related functioning. EE may be an important child and maternal trait associated with pre-treatment OCD severity and generalization of treatment gains. PMID- 22090188 TI - Representation of dynamic spatial configurations in visual short-term memory. AB - Locations of multiple stationary objects are represented on the basis of their global spatial configuration in visual short-term memory (VSTM). Once objects move individually, they form a global spatial configuration with varying spatial inter-object relations over time. The representation of such dynamic spatial configurations in VSTM was investigated in six experiments. Participants memorized a scene with six moving and/or stationary objects and performed a location change detection task for one object specified during the probing phase. The spatial configuration of the objects was manipulated between memory phase and probing phase. Full spatial configurations showing all objects caused higher change detection performance than did no or partial spatial configurations for static and dynamic scenes. The representation of dynamic scenes in VSTM is therefore also based on their global spatial configuration. The variation of the spatiotemporal features of the objects demonstrated that spatiotemporal features of dynamic spatial configurations are represented in VSTM. The presentation of conflicting spatiotemporal cues interfered with memory retrieval. However, missing or conforming spatiotemporal cues triggered memory retrieval of dynamic spatial configurations. The configurational representation of stationary and moving objects was based on a single spatial configuration, indicating that static spatial configurations are a special case of dynamic spatial configurations. PMID- 22090189 TI - Laparoscopic distal pancreatectomy and splenectomy for malignant tumors. AB - INTRODUCTION: Laparoscopic distal pancreatectomy has become the gold standard for benign tumors. As more surgeons have expertise in open and laparoscopic pancreatic surgery, increasing numbers of benign-appearing tumors are being removed via minimally invasive techniques and found to have malignancy on final pathology. Because of our growing experience in laparoscopic distal pancreatectomy, we have begun removing preoperatively suspected malignancies in the distal pancreas with minimally invasive techniques. METHODS: All cases were collected prospectively in a database and analyzed retrospectively. All cases begun laparoscopically with the intention of performing the resection with minimally invasive techniques were considered even if the operation was ultimately converted to an open procedure. RESULTS: A total of 12 cases have been attempted of which four required hand assistance and one required conversion to an open approach due to delayed bleeding from a calcified splenic artery that had been transected with laparoscopic GIA stapler device. In total, eight (67%) patients had malignant disease and four (33%) were found to have benign tumors. The median lymph node retrieval is 8 (range 3-16) with no positive margins. The morbidity rate is 17% with one reoperation (8%) and one mortality (8%) at 30 and 90 days. CONCLUSIONS: The laparoscopic approach to malignant pancreatic tumors is feasible with similar morbidity and mortality rates to benign series. When tumors are next to the confluence of the splenic portal vein, a hand-assisted approach may be adviseable. Calcified splenic arteries should be sought on preoperative imaging and either transected in non-calcified segments or controlled via open techniques via the hand port. PMID- 22090190 TI - Patient outcome in primary peritoneal dialysis patients versus those transferred from hemodialysis and transplantation. AB - BACKGROUND: According to the concept of integrated care, renal transplantation, peritoneal dialysis (PD), and hemodialysis (HD) should be considered three complementary methods of renal replacement therapy. This study tried to evaluate patient outcomes in three different groups of PD patients, namely primary PD patients, those transferred to PD with failing kidney transplant, and those transferred to PD from HD. METHOD: From January 1, 1995, to end of 2006 from 26 PD centers, 1,355 patients including demographic, clinical and laboratory data, which were monthly collected through questionnaires, were enrolled in the study. We compared patients' characteristics, factors affecting patient survival, and patient outcomes between primary PD patients (group 1, n = 1,067), patients transferred from transplantation (group 2, n = 43) and those transferred from HD (group 3, n = 245), which had been on HD for at least 3 months before switching to PD. RESULTS: There was no difference in the proportion of patients with diabetes in the three groups. Overall, 238 patients (17.5%) were transferred to HD but there was no significant difference in PD technique survival on between the three groups. Death occurred in 256 (24%), 3 (7%) and 65 (26.5%) subjects in groups 1, 2 and 3, respectively. Most patients (81.5%) in group 2 underwent re transplantation. The Kaplan-Meier survival rates were not different between the three groups. In the Cox multiple regression model, age, presence of diabetes and serum albumin level significantly influenced patient survival. CONCLUSION: We concluded that PD could be considered safe for patients experiencing complications on HD, as well as for those with renal transplantation. PMID- 22090191 TI - Fatal case of perforated appendicitis in an elderly CAPD patient. PMID- 22090192 TI - Variations in depression care and outcomes among high-risk mothers from different racial/ethnic groups. AB - PURPOSE. To examine variations in depression care and outcomes among high-risk pregnant and parenting women from different racial/ethnic groups served in community health centres. METHODS: As part of a collaborative care programme that provides depression treatment in primary care clinics for high-risk mothers, 661 women with probable depression (Patient Health Questionnaire-9 >= 10), who self reported race/ethnicity as Latina (n = 393), White (n = 126), Black (n = 75) or Asian (n = 67), were included in the study. Primary outcomes include quality of depression care and improvement in depression. A Cox proportional hazard model adjusting for sociodemographic and clinical characteristics was used to examine time to treatment response. RESULTS: We observed significant differences in both depression processes and outcomes across ethnic groups. After adjusting for other variables, Blacks were found to be significantly less likely to improve than Latinas [hazard ratio (HR): 0.53, 95% confidence interval (CI): 0.44-0.65]. Other factors significantly associated with depression improvement were pregnancy (HR: 1.52, 95% CI: 1.27-1.82), number of clinic visits (HR: 1.26, 95% CI: 1.17-1.36) and phone contacts (HR: 1.45, 95% CI: 1.32-1.60) by the care manager in the first month of treatment. After controlling for depression severity, having suicidal thoughts at baseline was significantly associated with a decreased likelihood of depression improvement (HR: 0.75, 95% CI: 0.67-0.83). CONCLUSIONS: In this racially and ethnically diverse sample of pregnant and parenting women treated for depression in primary care, the intensity of care management was positively associated with improved depression. There was also appreciable variation in depression outcomes between Latina and Black patients. PMID- 22090193 TI - The role of primary care professionals in women's experiences of cervical cancer screening: a qualitative study. AB - BACKGROUND: The UK Cervical Screening Programme, delivered mostly through primary care, commands impressive levels of public support. However, considerable evidence suggests that women find the experience of screening problematic. OBJECTIVE: To investigate this tension using women's accounts of cervical screening, with a view to informing practice to better meet their needs. METHODS: A qualitative interview study with 34 participants focussed on their experiences and understandings of cervical cancer screening in the UK. Analysis was based on the constant comparative method. RESULTS: The highly intimate and personal nature of the test is challenging, and many women report unsatisfactory experiences. Problematic issues include: embarrassment and discomfort (sometimes severe) in exposing an intimate and personal part of their body; surrendering control and finding the test painful, uncomfortable and personally threatening. Though there is an important role for primary health care professionals in easing discomfort and facilitating positive experiences, women often report feeling disappointed with how the procedure is conducted. Women suggest that practitioners' attempts to normalize the interaction and maintain a degree of detachment could have the perverse effect of making them feel more uncomfortable and that more personalization would be welcome. CONCLUSIONS: This work identifies the ways in which women may find personal engagement with cervical screening difficult and demonstrates the important role of primary care practitioners in contributing to women's experiences of the encounter. We draw on Erving Goffman's work on the 'interaction order' to explain some of the problems reported by women and to help inform good practice in primary care. PMID- 22090194 TI - Cardiac PET, CT, and MR: what are the advantages of hybrid imaging? AB - Cardiac hybrid imaging combines different imaging modalities in a way where both modalities equally contribute to image information. Hybrid positron emission tomography-computed tomography (PET-CT) imaging is a promising tool for evaluation of coronary artery disease (CAD) because it enables detection of coronary atherosclerotic lesions by CT angiography and their consequences on myocardial blood flow by PET perfusion in a single study. This appears to offer superior diagnostic accuracy in patients with intermediate risk for CAD compared with stand-alone imaging. Novel, commercially available hybrid scanners containing PET and magnetic resonance as well as development of targeted probes to evaluate molecular and cellular disease mechanisms are expected to provide many new applications for cardiac hybrid imaging. This article focuses on the advantages of cardiac hybrid imaging in the detection of CAD in light of currently available clinical data and discusses the potential future applications. PMID- 22090195 TI - Clopidogrel and PPI interaction: clinically relevant or not? AB - Proton pump inhibitors and clopidogrel are commonly prescribed medications, both alone and in combination. In January of 2009 the US Food and Drug Administration and the European Medicines Agency issued warnings with regard to the concomitant use of clopidogrel and proton pump inhibitors. Later that year, these warnings were limited to the proton pump inhibitor omeprazole. These warnings were largely based on in-vitro studies and observational analyses suggesting decreased efficacy of clopidogrel in the presence of proton pump inhibitors. Recent literature has suggested there may not be a clinically meaningful interaction. PMID- 22090197 TI - Suboptimal choice in nonhuman animals: rats commit the sunk cost error. AB - The present experiments investigated the sunk cost error, an apparently irrational tendency to persist with an initial investment, in rats. This issue is of interest because some have argued that nonhuman animals do not commit this error. Two or three fixed-ratio (FR) response requirements were arranged on one lever, and an escape option was arranged on a second lever. The FRs were of different sizes, and escaping was the behavior of interest. Several variables that might influence the decision to persist versus escape were manipulated: the number of trials with different FR schedules in an experimental session (Exps. 1 and 2), effort to escape (Exp. 2), and the size of the larger FR (Exp. 3). The sunk cost error would result in never escaping, and the optimal strategy would be to escape from the larger FR. The main variable that determined persisting versus escaping was the size of the large FR. Rats that escaped from the large FR apparently optimal behavior-did so at a suboptimal point, and hence committed the sunk cost error. PMID- 22090198 TI - Genome analysis of two type 6 echovirus (E6) strains recovered from sewage specimens in Greece in 2006. AB - Echovirus 6 (E6) is one of the main enteroviral serotypes that was isolated from cases of aseptic meningitis and encephalitis during the last years in Greece. Two E6 (LR51A5 and LR61G3) were isolated from the sewage treatment plant unit in Larissa, Greece, in May 2006, 1 year before their characterization from aseptic meningitis cases. The two isolates were initially found to be intra-serotypic recombinants in the genomic region VP1, a finding that initiated a full genome sequence analysis. In the present study, nucleotide, amino acid, and phylogenetic analyses for all genomic regions were conducted. For the detection of recombination events, Simplot and bootscan analyses were carried out. The continuous phylogenetic relationship in 2C-3D genomic region of strains LR51A5 and LR61G3 with E30 isolated in France in 2002-2005 indicated that the two strains were recombinants. SimPlot and Bootscan analyses confirmed that LR51A5 and LR61G3 carry an inter-serotypic recombination in the 2C genomic region. The present study provide evidence that recombination events occurred in the regions VP1 (intraserotypic) and non-capsid (interserotypic) during the evolution of LR51A5 and LR61G3, supporting the statement that the genomes of circulating enteroviruses are a mosaic of genomic regions of viral strains of the same or different serotypes. In conclusion, full genome sequence analysis of circulating enteroviral strains is a prerequisite to understand the complexity of enterovirus evolution. PMID- 22090199 TI - Assessment of metabolic modulation in free-living versus endosymbiotic Symbiodinium using synchrotron radiation-based infrared microspectroscopy. AB - The endosymbiotic relationship between coral hosts and dinoflagellates of the genus Symbiodinium is critical for the growth and productivity of coral reef ecosystems. Here, synchrotron radiation-based infrared microspectroscopy was applied to examine metabolite concentration differences between endosymbiotic (within the anemone Aiptasia pulchella) and free-living Symbiodinium over the light-dark cycle. Significant differences in levels of lipids, nitrogenous compounds, polysaccharides and putative cell wall components were documented. Compared with free-living Symbiodinium, total lipids, unsaturated lipids and polysaccharides were relatively enriched in endosymbiotic Symbiodinium during both light and dark photoperiods. Concentrations of cell wall-related metabolites did not vary temporally in endosymbiotic samples; in contrast, the concentrations of these metabolites increased dramatically during the dark photoperiod in free living samples, possibly reflecting rhythmic cell-wall synthesis related to light driven cell proliferation. The level of nitrogenous compounds in endosymbiotic cells did not vary greatly across the light-dark cycle and in general was significantly lower than that observed in free-living samples collected during the light. Collectively, these data suggest that nitrogen limitation is a factor that the host cell exploits to induce the biosynthesis of lipids and polysaccharides in endosymbiotic Symbiodinium. PMID- 22090200 TI - Physiological implications of pair-bond status in greylag geese. AB - In group-living vertebrates, reliable social allies play a decisive role in dealing with stressors. For example, support by social allies is known to dampen glucocorticoid responses. It remains unknown, however, how social embedding affects the sympatho-adrenergic axis as indicated by heart rate (HR) in non-human animals. We studied the relationships between HR, pair-bond status and distance from the pair-partner in twenty-five free-ranging greylag geese (Anser anser) in a natural social environment. In three individuals, we investigated HR responses following partner loss. Overall, we found a context- and sex-dependent difference in HR between paired and unpaired individuals, paired males having a lower HR during agonistic encounters, and unpaired females having a lower HR during resting. Also, in paired females HR increased with increasing distance from the partner. Our data suggest that HR is modulated by pair-bond status in greylag geese in a context- and sex-dependent manner, which may be representative for social vertebrates in general. Despite the low sample size, the present study indicates that proper social embedding may optimize an individual's physiological investment in the social domain. This reduces individual energy expenditure and may benefit health and reproductive success. PMID- 22090201 TI - Wild geese do not increase flight behaviour prior to migration. AB - Hypertrophy of the flight muscles is regularly observed in birds prior to long distance migrations. We tested the hypothesis that a large migratory bird would increase flight behaviour prior to migration, in order to cause hypertrophy of the flight muscles, and upregulate key components of the aerobic metabolic pathways. Implantable data loggers were used to record year-round heart rate in six wild barnacle geese (Branta leucopsis), and the amount of time spent in flight each day was identified. Time in flight per day did not significantly increase prior to either the spring or the autumn migration, both between time periods prior to migration (5, 10 and 15 days), or when compared with a control period of low activity during winter. The lack of significant increase in flight prior to migration suggests that approximately 22 min per day is sufficient to maintain the flight muscles in condition for prolonged long-distance flight. This apparent lack of a requirement for increased flight activity prior to migration may be attributable to pre-migratory mass gains in the geese increasing workload during short flights, potentially prompting hypertrophy of the flight muscles. PMID- 22090202 TI - Susceptibility of the male fitness phenotype to spontaneous mutation. AB - Adult reproductive success can account for a large fraction of male fitness, however, we know relatively little about the susceptibility of reproductive traits to mutation-accumulation (MA). Estimates of the mutational rate of decline for adult fitness and its components are controversial in Drosophila melanogaster, and post-copulatory performance has not been examined. We therefore separately measured the consequences of MA for total male reproductive success and its major pre-copulatory and post-copulatory components: mating success and sperm competitive success. We also measured juvenile viability, an important fitness component that has been well studied in MA experiments. MA had strongly deleterious effects on both male viability and adult fitness, but the latter declined at a much greater rate. Mutational pressure on total fitness is thus much greater than would be predicted by viability alone. We also noted a significant and positive correlation between all adult traits and viability in the MA lines, suggesting pleiotropy of mutational effect as required by 'good genes' models of sexual selection. PMID- 22090203 TI - Does prey size matter? Novel observations of feeding in the leatherback turtle (Dermochelys coriacea) allow a test of predator-prey size relationships. AB - Optimal foraging models predict that large predators should concentrate on large prey in order to maximize their net gain of energy intake. Here, we show that the largest species of sea turtle, Dermochelys coriacea, does not strictly adhere to this general pattern. Field observations combined with a theoretical model suggest that a 300 kg leatherback turtle would meet its energetic requirements by feeding for 3-4 h a day on 4 g jellyfish, but only if prey were aggregated in high-density patches. Therefore, prey abundance rather than prey size may, in some cases, be the overriding parameter for foraging leatherbacks. This is a classic example where the presence of small prey in the diet of a large marine predator may reflect profitable foraging decisions if the relatively low energy intake per small individual prey is offset by high encounter rates and minimal capture and handling costs. This study provides, to our knowledge, the first quantitative estimates of intake rate for this species. PMID- 22090204 TI - Evidence for a vertebrate catapult: elastic energy storage in the plantaris tendon during frog jumping. AB - Anuran jumping is one of the most powerful accelerations in vertebrate locomotion. Several species are hypothesized to use a catapult-like mechanism to store and rapidly release elastic energy, producing power outputs far beyond the capability of muscle. Most evidence for this mechanism comes from measurements of whole-body power output; the decoupling of joint motion and muscle shortening expected in a catapult-like mechanism has not been demonstrated. We used high speed marker-based biplanar X-ray cinefluoroscopy to quantify plantaris muscle fascicle strain and ankle joint motion in frogs in order to test for two hallmarks of a catapult mechanism: (i) shortening of fascicles prior to joint movement (during tendon stretch), and (ii) rapid joint movement during the jump without rapid muscle-shortening (during tendon recoil). During all jumps, muscle fascicles shortened by an average of 7.8 per cent (54% of total strain) prior to joint movement, stretching the tendon. The subsequent period of initial joint movement and high joint angular acceleration occurred with minimal muscle fascicle length change, consistent with the recoil of the elastic tendon. These data support the plantaris longus tendon as a site of elastic energy storage during frog jumping, and demonstrate that catapult mechanisms may be employed even in sub-maximal jumps. PMID- 22090205 TI - Metapopulation models for seasonally migratory animals. AB - Metapopulation models are widely used to study species that occupy patchily distributed habitat, but are rarely applied to migratory species, because of the difficulty of identifying demographically independent subpopulations. Here, we extend metapopulation theory to describe the directed seasonal movement of migratory populations between two sets of habitat patches, breeding and non breeding, with potentially different colonization and extinction rates between patch types. By extending the classic metapopulation model, we show that migratory metapopulations will persist if the product of the two colonization rates exceeds the product of extinction rates. Further, we develop a spatially realistic migratory metapopulation model and derive a landscape metric-the migratory metapopulation capacity-that determines persistence. This new extension to metapopulation theory introduces an important tool for the management and conservation of migratory species and may also be applicable to model the dynamics of two host-parasite systems. PMID- 22090206 TI - Transgenerational effects of parent and grandparent gender on offspring development in a biparental beetle species. AB - Parental effects on offspring life-history traits are common and increasingly well-studied. However, the extent to which these effects persist into offspring in subsequent generations has received less attention. In this experiment, maternal and paternal effects on offspring and grand-offspring were investigated in the biparental burying beetle Nicrophorus vespilloides, using a split-family design. This allowed the separation of prenatal and postnatal transgenerational effects. Grandparent and parent gender were found to have a cumulative effect on offspring development and may provide a selection pressure on the division of parental investment in biparental species. PMID- 22090207 TI - Social status gates social attention in humans. AB - Humans tend to shift attention in response to the averted gaze of a face they are fixating, a phenomenon known as gaze cuing. In the present paper, we aimed to address whether the social status of the cuing face modulates this phenomenon. Participants were asked to look at the faces of 16 individuals and read fictive curriculum vitae associated with each of them that could describe the person as having a high or low social status. The association between each specific face and either high or low social status was counterbalanced between participants. The same faces were then used as stimuli in a gaze-cuing task. The results showed a greater gaze-cuing effect for high-status faces than for low-status faces, independently of the specific identity of the face. These findings confirm previous evidence regarding the important role of social factors in shaping social attention and show that a modulation of gaze cuing can be observed even when knowledge about social status is acquired through episodic learning. PMID- 22090208 TI - Glycemic targets and approaches to management of the patient with critical illness. AB - Hyperglycemia during critical illness is associated with adverse outcome. The proof-of-concept Leuven studies assessed causality, and revealed that targeting strict normoglycemia (80-110 mg/dL) with insulin improved outcome compared with tolerating hyperglycemia to the renal threshold (215 mg/dL). A large multicenter trial (NICE-SUGAR [Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation]) found an intermediate blood glucose target (140 180 mg/dL) safer than targeting normoglycemia. Differences in design and in execution of glycemic control at the bedside may have contributed to these results. In NICE-SUGAR (Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation), the blood-glucose target range in the control group was lower, there were problems to reach and maintain normoglycemia in the intervention group, and inaccurate handheld blood glucose meters and variable blood sampling sites were allowed. Inaccurate tools led to insulin dosing errors with consequently (undetected) hypoglycemia and unacceptable blood glucose variability. Also, the studies were done superimposed upon different nutritional strategies. Thus, such differences do not allow simple, evidence based recommendations for daily practice, but an intermediate blood glucose target may be preferable while awaiting better tools to facilitate safely reaching normoglycemia. PMID- 22090209 TI - Amino acids 473V and 598P of PB1 from an avian-origin influenza A virus contribute to polymerase activity, especially in mammalian cells. AB - It has been reported that the avian-origin influenza A virus PB1 protein (avian PB1) enhances influenza A virus polymerase activity in mammalian cells when it replaces the human-origin PB1 protein (human PB1). Characterization of the amino acid residues that contribute to this enhancement is needed. In this study, it was found that PB1 from an avian-origin influenza A virus [A/Cambodia/P0322095/2005, H5N1 (Cam)] could enhance the polymerase activity of an attenuated human isolated virus, A/WSN/33, carrying the PB2 K627E mutation (WSN627E) in vitro. Furthermore, 473V and 598P in the Cam PB1 were identified as the residues responsible for this enhanced activity. The results from recombinant virus experiments demonstrated the contribution of PB1 amino acids 473V and 598P to polymerase activity in mammalian cells and in mice. Interestingly, 473V is conserved in pH1N1 viruses from the 2009 pandemic. Substitution of 473V by leucine in pH1N1 PB1 led to a decreased viral polymerase activity and a lower growth rate in mammalian cells, suggesting that the PB1 473V also plays a role in maintaining efficient virus replication of the pH1N1 virus. Thus, it was concluded that two amino acids in avian-origin PB1, 473V and 598P, contribute to the polymerase activity of the H5N1 virus, especially in mammalian cells, and that 473V in PB1 also contributes to efficient replication of the pH1N1 strain. PMID- 22090210 TI - Echovirus 11 infection induces dramatic changes in the actin cytoskeleton of polarized Caco-2 cells. AB - Binding of echovirus 11 strain 207 (EV11-207) to Caco-2 monolayers results in rapid transfer of the virus to tight junctions prior to uptake. Using a confocal microscopy based-method, this study quantified the spatiotemporal distribution of actin during the time course of infection by EV11-207 in Caco-2 polarized cells. It was found that binding of EV11-207 to the apical surface resulted in rapid rearrangement of the actin cytoskeleton, concomitant with transport of the virus particles to tight junctions. By interfering with the actin network dynamics, the virus remained trapped at the cell surface, leading to abortion of infection. In addition, it was observed that at 4 h post-infection, concomitant with the detection of virus replication, actin filament was depolymerized and degraded. Finally, it was shown that the mechanisms leading to loss of actin were independent of viral genome synthesis, indicating a potential role for the viral protein synthesis seen in late infection. These data confirmed a previous study on the requirement for an intact actin cytoskeleton for EV11-207 to infect cells and reinforce the notion of actin cytoskeleton subversion by picornaviruses during infection in polarized epithelial cells. PMID- 22090211 TI - Characterization of intracellular localization of PrP(Sc) in prion-infected cells using a mAb that recognizes the region consisting of aa 119-127 of mouse PrP. AB - Generation of an abnormal isoform of the prion protein (PrP(Sc)) is a key aspect of the propagation of prions. Elucidation of the intracellular localization of PrP(Sc) in prion-infected cells facilitates the understanding of the cellular mechanism of prion propagation. However, technical improvement in PrP(Sc) specific detection is required for precise analysis. Here, we show that the mAb 132, which recognizes the region adjacent to the most amyloidogenic region of PrP, is useful for PrP(Sc)-specific detection by immunofluorescence assay in cells pre-treated with guanidine thiocyanate. Extensive analysis of the intracellular localization of PrP(Sc) in prion-infected cells using mAb 132 revealed the presence of PrP(Sc) throughout endocytic compartments. In particular, some of the granular PrP(Sc) signals that were clustered at peri nuclear regions appeared to be localized in an endocytic recycling compartment through which exogenously loaded transferrin, shiga and cholera toxin B subunits were transported. The granular PrP(Sc) signals at peri-nuclear regions were dispersed to the peripheral regions including the plasma membrane during incubation at 20 degrees C, at which temperature transport from the plasma membrane to peri-nuclear regions was impaired. Conversely, dispersed PrP(Sc) signals appeared to return to peri-nuclear regions within 30 min during subsequent incubation at 37 degrees C, following which PrP(Sc) at peri-nuclear regions appeared to redisperse again to peripheral regions over the next 30 min incubation. These results suggest that PrP(Sc) is dynamically transported along with the membrane trafficking machinery of cells and that at least some PrP(Sc) circulates between peri-nuclear and peripheral regions including the plasma membrane via an endocytic recycling pathway. PMID- 22090212 TI - Differences in the mechanism of inoculation between a semi-persistent and a non persistent aphid-transmitted plant virus. AB - Inoculation of the semi-persistent cauliflower mosaic virus (CaMV, genus Caulimovirus) is associated with successive brief (5-10 s) intracellular stylet punctures (pd) when aphids probe in epidermal and mesophyll cells. In contrast to non-persistent viruses, there is no evidence for which of the pd subphases (II-1, II-2 and II-3) is involved in the inoculation of CaMV. Experiments were conducted using the electrical penetration graph (EPG) technique to investigate which particular subphases of the pd are associated with the inoculation of CaMV to turnip by its aphid vector Brevicoryne brassicae. In addition, the same aphid species/test plant combination was used to compare the role of the pd subphases in the inoculation of the non-persistent turnip mosaic virus (TuMV, genus Potyvirus). Inoculation of TuMV was found to be related to subphase II-1, confirming earlier results, but CaMV inoculation appeared to be related exclusively to subphase II-2 instead. The mechanism of CaMV inoculation and the possible nature of subphase II-2 are discussed in the scope of our findings. PMID- 22090213 TI - Hazara virus infection is lethal for adult type I interferon receptor-knockout mice and may act as a surrogate for infection with the human-pathogenic Crimean Congo hemorrhagic fever virus. AB - Hazara virus (HAZV) is closely related to the Crimean-Congo hemorrhagic fever virus (CCHFV). HAZV has not been reported to cause human disease; work with infectious material can be carried out at containment level (CL)-2. By contrast, CCHFV causes a haemorrhagic fever in humans and requires CL-4 facilities. A disease model of HAZV infection in mice deficient in the type I interferon receptor is reported in this study. Dose-response effects were seen with higher doses, resulting in a shorter time to death and earlier detection of viral loads in organs. The lowest dose of 10 p.f.u. was still lethal in over 50 % of the mice. Histopathological findings were identified in the liver, spleen and lymph nodes, with changes similar to a recent mouse model of CCHFV infection. The findings demonstrate that inoculation of mice with HAZV may act as a useful surrogate model for the testing of antiviral agents against CCHFV. PMID- 22090215 TI - [Editorial]. PMID- 22090214 TI - Infection of human alveolar macrophages by human coronavirus strain 229E. AB - Human coronavirus strain 229E (HCoV-229E) commonly causes upper respiratory tract infections. However, lower respiratory tract infections can occur in some individuals, indicating that cells in the distal lung are susceptible to HCoV 229E. This study determined the virus susceptibility of primary cultures of human alveolar epithelial cells and alveolar macrophages (AMs). Fluorescent antibody staining indicated that HCoV-229E could readily infect AMs, but no evidence was found for infection in differentiated alveolar epithelial type II cells and only a very low level of infection in type II cells transitioning to the type I-like cell phenotype. However, a human bronchial epithelial cell line (16HBE) was readily infected. The innate immune response of AMs to HCoV-229E infection was evaluated for cytokine production and interferon (IFN) gene expression. AMs secreted significant amounts of tumour necrosis factor alpha (TNF-alpha), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and macrophage inflammatory protein 1beta (MIP-1beta/CCL4) in response to HCoV-229E infection, but these cells exhibited no detectable increase in IFN-beta or interleukin-29 in mRNA levels. AMs from smokers had reduced secretion of TNF alpha compared with non-smokers in response to HCoV-229E infection. Surfactant protein A (SP-A) and SP-D are part of the innate immune system in the distal lung. Both surfactant proteins bound to HCoV-229E, and pre-treatment of HCoV-229E with SP-A or SP-D inhibited infection of 16HBE cells. In contrast, there was a modest reduction in infection in AMs by SP-A, but not by SP-D. In summary, AMs are an important target for HCoV-229E, and they can mount a pro-inflammatory innate immune response to infection. PMID- 22090216 TI - What has changed in the treatment of ST-segment elevation myocardial infarction in Poland in 2003-2009? Data from the Polish Registry of Acute Coronary Syndromes (PL-ACS). AB - BACKGROUND: A substantial progress has been made in Poland in the field of acute coronary syndromes (ACS) management over the last 10 years. AIM: To present the data from the Polish Registry of Acute Coronary Syndromes (PL-ACS) collected between 2003 and 2009. Changes in treatment strategies and outcomes in ST-segment myocardial infarction (STEMI) were analysed. METHODS: We analysed patients enrolled to the PL-ACS Registry - a nationwide multicenter, prospective observational study of consecutive patients hospitalised with ACS in Poland. RESULTS: Overall, 284,162 patients with ACS were enrolled in 512 centres including 88 invasive cardiology centres. The STEMI was diagnosed in 35-36% of these patients in 2003-2005, and this proportion remained stable at 30% to 32% in 2006-2009. The mean age of STEMI patients increased from 62.5 years in 2003 to 64.5 in 2009. During this period, women represented 32.7% to 34.6% of the STEMI patients. Proportion of patients presenting with pulmonary oedema or cardiogenic shock decreased with time, from 15.5% in 2003 to 8% in 2009. Delays to reperfusion tended to reduce over time: pain-to- -admission time was 240 min in 2005 and 229 min in 2009 and door-to-balloon time was 32 and 25 min in 2005 and 2009, respectively, with the delay being longer in the elderly population. The proportion of patients undergoing coronary angiography showed a constant increase, from 55% in 2003 to 84% in 2009. Percutaneous coronary intervention was performed in 51% and 78% of patients in 2003 and 2009, respectively. At the same time, the proportion of patients undergoing thrombolysis declined from 14% to 1%. Aspirin, beta-blocker, statin and ACE inhibitor use was constantly high, while nitrate use declined from 82% to 15%. The proportion of patients receiving clopidogrel increased from 40% to 97% over the analysed period. Significant reductions in mortality rates were observed: in-hospital mortality decreased from 11.9% to 6.4%; 30-day mortality from 13.5% to 9.6%; and 12-month mortality from 19.8% to 15.4% in 2003 and 2009, respectively. Invasive treatment strategy was associated with better in-hospital and long-term patient survival. CONCLUSIONS: The PL-ACS Registry results demonstrate low short- and long-term mortality rates in STEMI patients, mainly due to frequent use of interventional strategy, satisfactory logistics and appropriate drug therapy used. As a consequence, hospitalisation time has shortened. However, there are several issues that need to be improved such as shortening of pre- -hospital delays and increasing the rate of invasive treatment in patients presenting with cardiogenic shock. PMID- 22090217 TI - [Another success of polish invasive cardiologists-improve the outcomes of heart attack]. PMID- 22090218 TI - Diagnostic accuracy of pre-operative NT-proBNP level in predicting short-term outcomes in coronary surgery: a pilot study. AB - BACKGROUND: B-type natriuretic peptides (BNP) are acknowledged markers of acute and chronic heart failure. Insufficient data exist, however, regarding their diagnostic usefulness in cardiac surgery, particularly in coronary patients. AIM: To assess diagnostic accuracy of preoperative value of NT-proBNP level as a predictor of short-term postoperative complications in subjects undergoing coronary artery bypass grafting (CABG). METHODS: This pilot study included 100 consecutive patients scheduled for elective CABG, including 24 females and 76 males (mean age 65.9 +/- 9.1 years). Exclusion criteria were: significant valvular disorders, off-pump procedure, renal failure (GFR < 60 mL/min/1.73 m2), low ejection fraction (< 30%), intra-aortic balloon pump counterpulsation (IABP), use of inotropic agents, atrial fibrillation (AF), and implanted pacemaker or defibrillator. The NT-proBNP level was measured on the day of the surgery before induction of anaesthesia. We investigated short-term postoperative complications, defined as those occurring within 30 days or before hospital discharge. RESULTS: Median NT-proBNP concentration was 526.0 pg/mL (IQR 156.0-1150.0). None of patients died postoperatively. Excessive drainage (> 850 mL) was found in 13 (13%) patients and 22 (22%) subjects required transfusions. Prolonged mechanical ventilation (> 12 h) was necessary in 15 (15%) patients and respiratory failure occurred in 2 (2%) of them. Postoperative AF was present in 34 (34%) subjects. Perioperative myocardial infarction was diagnosed in 2 (2%) persons. Low cardiac output was present in 9 (9%) patients. Haemodynamic support with the use of IABP was necessary in 7 (7%) patients and inotropic drugs were used in 61 (61%) subjects. Stroke or delirium was diagnosed in 1 (1%) subject. The NT-proBNP level correlated with the operative risk estimated by logistic and additive EuroSCORE: r = 0.558 (95% CI 0.406-0.680; p < 0.001) and r = 0.551 (95% CI 0.397-0.674; p < 0.001), respectively. The NT-proBNP level correlated significantly with the length of Intensive Care Unit (ICU) stay and hospital stay: r = 0.412 (95% CI 0.238-0.566; p < 0.001) and r = 0.547 (95% CI 0.393-0.672; p < 0.001), respectively. The NT-proBNP level was a predictor of postoperative prolonged mechanical ventilation, respiratory failure, AF, IABP use, inotropic support and postoperative platelet transfusions (p < 0.05 for all). However, good or very good diagnostic accuracy was found only in relation to mechanical ventilation (AUROC = 0.854), respiratory insufficiency (AUROC = 0.867), IABP use (AUROC = 0.889), and milrinone use (AUROC = 0.929). CONCLUSIONS: Preoperative assessment of NT-proBNP level in CABG patients could be a valuable diagnostic method for predicting several postoperative complications, especially pulmonary outcomes and requirement for haemodynamic support, and it correlated with the length of ICU stay and hospital stay. PMID- 22090219 TI - [Can BNP may affect eligibility for coronary artery bypass grafting?]. PMID- 22090220 TI - Myocardial ischaemia in systemic lupus erythematosus: detection and clinical relevance. AB - BACKGROUND: Severe cardiovascular complications are among the most important causes of mortality in systemic lupus erythematosus (SLE) patients. AIM: To assess the usefulness of echocardiography, ECG, and coronary artery calcium scoring (CACS) in the detection of myocardial ischaemia in SLE patients compared to single photon emission computerised tomography (SPECT) and to assess their five-year follow-up. METHODS: In 50 consecutive SLE patients (mean age 39.2 +/- 12.9 years, 90% female), clinical assessment, resting and exercise ECG and echocardiography, multidetector computed tomography - based CACS and SPECT studies (Tc-99m sestamibi) were performed. Patients were then followed for five years. RESULTS: SPECT revealed perfusion defects in 25 (50%) patients; persistent defects in 18 (36%) and exercise-induced defects in seven (14%) subjects. No typical ischaemic heart disease clinical symptoms, signs of ischaemia in resting ECG, or left ventricular contractility impairment in echocardiography were observed. Signs of ischaemia in exercise ECG were found in 17 (34%) patients. The CACS ranged from 1 to 843.2 (median 23.15), and coronary calcifications were observed in 12 (24%) patients. Compared to the SPECT study, exercise ECG had 68% sensitivity and 100% specificity in detecting myocardial ischaemia, while CACS had only 28% sensitivity and 58% specificity. During follow-up, one patient who showed myocardial perfusion defects and the highest calcium score (843.2) at baseline, developed CCS II class symptoms of myocardial ischaemia. Coronary angiography was not performed because of severe anaemia; the patient died three months later. In two other patients with perfusion defects and calcium deposits at baseline, CCS I class symptoms were observed; coronary angiography showed only thin calcified coronary plaques that were haemodynamically insignificant. CONCLUSIONS: In about half of relatively young, mostly female, SLE patients, SPECT shows myocardial perfusion defects, with coronary calcifications present in one quarter of them. While ECG and echocardiography may not reveal any pathology, ECG exercise test can identify these patients with high specificity. In patients with a negative SPECT, the short-term prognosis is good, while in patients with perfusion defects and coronary calcifications, the clinical symptoms of myocardial ischaemia could occurr. However, at a low calcium score ( < 150), the short-term risk of significant atherosclerosis progression is low. PMID- 22090221 TI - Stent implantation into the interatrial septum in patients with univentricular heart and a secondary restriction of interatrial communication. AB - BACKGROUND: Presence of a restrictive interatrial communication in patients with univentricular anatomy significantly affects surgical outcomes. In patients with univentricular hearts, wide open atrial communication leads to lower pulmonary artery pressure, which is one of the most important factors influencing the success of bidirectional Glenn and Fontan operations. In some patients, recurrence of restricted interatrial communication can be observed despite initially successful interventional or surgical creation of unrestrictive interatrial communication. AIM: To evaluate efficacy of stent implantation into the interatrial septum in patients with univentricular heart and a secondary restriction of interatrial communication. METHODS: In 2006-2010, we created unrestrictive interatrial communication by stent implantation into the interatrial septum in 7 children with univentricular anatomy with systemic right ventricle (4 patients with hypoplastic left heart syndrome and 3 patients with mitral atresia). In all patients we diagnosed recurrent restriction of interatrial communication despite prior surgical or interventional creation of unrestrictive interatrial communication. Patient age at stent implantation was 3 to 30 months. Maximal systolic pressure gradient between the left and the right atrium was 6-29 mm Hg and left atrial pressure ranged from 20/17/19 mm Hg to 40/29/32 mm Hg. In all patients, we implanted a Palmaz-Genesis stent (length 18 29 mm) with subsequent balloon redilatation. RESULTS: In all 7 patients, we created unrestrictive interatrial communication with mean pressure gradient reduction from 13.14 mm Hg to 0.86 mm Hg (p < 0.006). Mean interatrial communication diameter increased from 4.14 mm to 10.57 mm (p < 0.0001). CONCLUSIONS: Percutaneous stent implantation into the interatrial septum in children with univentricular heart and secondary restriction of interatrial communication is a safe and effective method. Kardiol Pol 2011; 69, 11: 1137 1141. PMID- 22090222 TI - [A few comments on the septal stenting]. PMID- 22090223 TI - QT dispersion in patients with Churg-Strauss syndrome. AB - BACKGROUND: Churg-Strauss syndrome (CSS) is a rare, systemic necrotising small and middle-sized vessel vasculitis, accompanied by blood eosinophilia, eosinophil infiltration of various tissues and bronchial asthma. Cardiac injury caused by myocardial eosinophilic infiltration and/or vasculitis in CSS seems to be very common. Active inflammatory process accompanied by myocardial fibrosis has been described in this population even despite disease remission. Nevertheless, little is known about the possible myocardial repolarisation abnormalities in CSS which may lead to life-threatening ventricular arrhythmias. AIM: To evaluate myocardial repolarisation in CSS patients at the time of initial diagnosis and during the last disease remission. METHODS: In 20 CSS patients (8 male, 12 female) QT dispersion (QTd) and QTc dispersion (QTcd) calculated from heart rate corrected QT (QTc) from the surface 12-lead electrocardiograms were measured at the time of initial diagnosis and during the last disease remission. As a control group, 20 sex- and age-matched healthy volunteers were studied. Transthoracic echocardiography was performed in all CSS patients at remission and in the control group. RESULTS: QTcd was higher in CSS (n = 20) than in healthy controls (n = 20) in each period of time: at the time of initial diagnosis (45.4 +/- 14.2 vs 26.1 +/- 6.5, p < 0.0001) and at the remission (38.6 +/- 13.4 vs 26.1 +/- 6.5, p = 0.002). At the time of initial diagnosis in CSS patients with heart involvement (n = 13), when compared to patients without heart involvement, (n = 7), both QTcd (52.2 +/- 12.1 vs 34.7 +/- 10.7, p = 0.007) and QTd (37.7 +/- 12.7 vs 24 +/- 11.4, p = 0.008) were higher, and this difference remained significant at remission only for QTcd (46.7 +/- 13.2 vs 33.1 +/- 10.8, p = 0.03). No significant correlation was observed between QTcd/QTd and disease activity (measured using the Birmingham Vasculitis Activity Score - BVAS), eosinophil blood count, presence of ANCA, nor the duration of the disease. CONCLUSIONS: The most pronounced increased QTcd was detected in the CSS patients with cardiac involvement at the time of initial diagnosis and remained higher at remission in all CSS patients when compared to healthy controls. Nevertheless, in the CSS patients, QTcd remains within the normal ranges, which may explain the relatively small number of ventricular arrhythmias in these patients. PMID- 22090224 TI - [Churg-Strauss syndrome - frequent heart seizure]. PMID- 22090225 TI - Which standard biomarkers are useful for the evaluation of myocardial injury after pulmonary vein isolation with cryoballoon? AB - BACKGROUND: Many studies have used creatinine kinase (CK), myocardial bound for CK (CK-MB), and cardiac troponin I (cTnI) and T (cTnT) to evaluate myocardial cells injury after ablation. We applied measurements of the blood concentration of cardio-specific biomarkers as surrogates for the injured cell mass. AIM: To clarify which of the standard biomarkers are useful in the evaluation and quantification of lesions produced by cryoballoon ablation (CBA) during pulmonary vein isolation. METHODS: The CBA was performed in 33 patients with atrial fibrillation. Blood samples were obtained before CBA and one, six, and 24 h after CBA. We analysed CK, CK-MB and cTnI. RESULTS: A significant increase of all biomarkers was observed at each hour of collection as compared to the baseline measurement. Maximum median peak levels occurred at 6 h. Pathological values of CK, CK-MB and cTnI were observed in 94%, 100% and 100% of patients, respectively. Both maximum CK and CK-MB values correlated with median temperature (p < 0.05) reached during CBA. Additionally, CK-MB correlated with total cryo-time (p < 0.03). CONCLUSIONS: The CK-MB is the best biochemical marker for the evaluation of myocardial injury after CBA. The cTnI can be useful as an additional parameter of myocardial injury after CBA. PMID- 22090226 TI - [Cryoablation balloon - a breakthrough in the treatment of atrial fibrillation]. PMID- 22090227 TI - Comparison of intravascular and conventional hypothermia after cardiac arrest. AB - BACKGROUND: Therapeutic hypothermia is currently the best-documented method of improving neurological outcomes in patients after cardiac arrest and successful resuscitation. There is a variety of methods for lowering body temperature. However, there are no data showing that any specific method of cooling improves the results or increases survival. A simple method involving surface cooling and ice-cold intravenous fluids, as well as more technologically advanced methods, are used in clinical practice. One of the more advanced methods is intravascular hypothermia, during which cooling is carried out with the use of a special catheter located in the central vein. AIM: To compare cooling with the use of intravascular hypothermia and cooling using the traditional method. METHODS: A prospective study was performed in 41 patients with acute coronary syndromes who did not regain consciousness after out-of-hospital or in-hospital cardiac arrest and restoration of spontaneous circulation. Therapeutic hypothermia (32-34 degrees C) was obtained with the use of an intravascular method (group A, n = 20) or a traditional method (group B, n = 21) for a period of 24 hours. Intravascular cooling involved the use of a catheter inserted in the femoral vein connected to a heat exchanger (Alsius Coolgard, Zoll, Chelmsford, MA, USA). Traditional cooling was carried out using uncontrolled surface cooling, ice-cold intravenous fluids and ice-cold gastric lavage. Nasopharyngeal and urinary bladder temperatures were recorded hourly. The main analysed temperature was the urinary bladder temperature, as the heat exchanger in the intravascular hypothermia group was controlled by the readings taken from this site. Temperature profiles were compared. RESULTS: Temperature < 34 degrees C was reached in 19 (95.0%) patients in group A and in 11 (52.4%) patients in group B (p = 0.004). Stable temperature profile (temperature in the range 32-34 degrees C during the final 12 h of cooling) was reached in 16 (80%) patients in group A and in three (14.3%) patients in group B (p < 0.001). Periods of inadequate cooling (temperature > 34 degrees C) and temperature overshoots (temperature < 32 degrees C) were significantly more frequent in group B. Temperature profiles were significantly different in both groups in the readings taken from both sites. CONCLUSIONS: The presented technique of intravascular hypothermia provides more precise temperature control in comparison with the traditional method. PMID- 22090228 TI - Therapeutic hypothermia in out-of-hospital cardiac arrest patients is included in the European Resuscitation Council Advanced Life Support Algorithm 2010 for treatment of post-cardiac-arrest-syndrome. PMID- 22090229 TI - [Percutaneous coronary intervention and aortic valve implantation in a patient with breast cancer]. AB - We present a case of a 70 year-old female with severe aortic stenosis, multivessel coronary artery disease and breast cancer who successfully underwent complex percutaneous coronary revascularisation, transapical aortic valve implantation and mastectomy. PMID- 22090230 TI - [Severe pulmonary embolism in a young marijuana smoker]. AB - It is a popular belief, that marijuana smoking is not harmful to health. Some publications, however, suggest its possible association with mental, respiratory and cardiovascular complications, but not with venous thromboembolism. The authors describe a case of severe pulmonary embolism in a mildly obese, 22 year old marijuana and tobacco smoker. After thrombolysis, rapid haemodynamic improvement was observed, contrary to slow regression of concomitant deep vein thrombosis during anticoagulation with warfarin. Toxycologic assessment of urine cannabinols was positive for two months. In trombophilia screening only moderate hyperhomocysteinaemia (not related to MTHFR C667T polymorphism) was found. PMID- 22090231 TI - [The man from the kingdom of the near-dead - modern treatment of pulmonary hypertension]. AB - Pulmonary arterial hypertension (PAH) is a rare and severe condition characterised by a progressive increase in pulmonary vascular resistance. Two decades ago patients with idiopathic PAH were defined as the people from the kingdom of near- -dead because of poor survival. The progress in treatment of PAH was made, however the disease is still severe and not curable. We present a 26 year-old male patient diagnosed with idiopathic PAH. The clinical course was complicated by progressive worsening, hemoptysis and thrombocytopenia. Treatment with treprostinil and bronchial artery embolisation was started, resulting in symptomatic and functional improvement. PMID- 22090232 TI - [The concomitance of pericarditis constrictiva in patient with Silver-Russell syndrome, primary hyperparathyroidism and oncologic history: causal coincidence or pathogenetic sequence?]. AB - The most common cause of calcific pericarditis is idiopathic. We report a case of a 24 year-old woman with Silver-Russell syndrome, history of Wilms' tumour in childhood, constrictive pericarditis and primary hyperparathyroidism. We analyse pathologic mechanisms of disseminated calcification and possible genetic factors that may contribute to aetiology and clinical presentation of calcific pericarditis. PMID- 22090233 TI - [Clinical and diagnostic aspects of Barth syndrome (X-linked cardiomyopathy)]. PMID- 22090234 TI - [Cardio-renal syndrome in patients with heart failure: pathophysiology, epidemiology and clinical significance]. PMID- 22090235 TI - [Fungal endocarditis of mitral and aortic biological prosthetic valves]. AB - We present a rare case of fungal (Candida albicans) endocarditis on the two (mitral and aortic) biological prosthetic valves. Vegetations were detected by transthoracic echocardiography and confirmed by transesophageal echocardiography. PMID- 22090236 TI - [ST-elevation myocardial infarction caused by very late stent thrombosis]. AB - The case of a 46 year-old man suffering from diabetes mellitus and dyslipidaemia hospitalised with acute coronary syndrome with ST-segment elevation caused by very late in-stent thrombosis is presented. PMID- 22090238 TI - [Severe tricuspid regurgitation due to ventricular pacing lead - a case report]. AB - We present a case of severe symptomatic tricuspid valve regurgitation due to shifting of the septal leaflet of the valve toward the interventricular septum by a permanent ventricular pacemaker lead, making coaptation of the tricuspid leflats in systole impossible. PMID- 22090239 TI - [Tricuspid regurgitation after pacemaker implantation, or how important it is to fix the electrode]. PMID- 22090240 TI - [Summary of the article: Jolly SS, Yusuf S, Cairns J et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet, 2011; 307: 1409-1420]. PMID- 22090241 TI - [Not Available]. PMID- 22090242 TI - [Multiple valve disease - a complex problem requiring an individualised approach to diagnostics and treatment]. PMID- 22090243 TI - [Catheter-based renal sympathetic denervation for the treatment of resistant arterial hypertension in Poland - experts consensus statement]. PMID- 22090244 TI - [Letter to the editor]. PMID- 22090245 TI - Revision surgery for persistent and recurrent carpal tunnel syndrome and for failed carpal tunnel release. AB - BACKGROUND: Carpal tunnel release is one of the most frequently performed hand operations. However, persistent, recurrent, or completely new symptoms following carpal tunnel release remain a difficult problem. METHODS: A retrospective review of the surgical findings and outcomes of 50 consecutive patients who had undergone 55 revision carpal tunnel operations was performed. RESULTS: The initial carpal tunnel release was an endoscopic technique in 34 hands and an open technique in 21 hands. Thirty-four hands continued to have persistent symptoms, 18 hands had recurrent symptoms, and three hands had completely new symptoms. Reexploration revealed incomplete release in 32 patients. Circumferential fibrosis around the median nerve was found in all patients. Forty-six percent of patients with recurrent symptoms had slight palmar subluxation of the median nerve. External neurolysis was performed in 41, epineurectomy was performed in 15, synovial or hypothenar fat flap coverage was performed in eight, and radial forearm adipofascial flap coverage was performed in three hands. Symptomatic improvement following revision surgery after open carpal tunnel release was slightly better (90 percent) compared with after endoscopic carpal tunnel release (76 percent), but complete relief of symptoms following revision surgery was similar after open (57 percent) or endoscopic (56 percent) techniques. Ten patients (20 percent) showed no improvement and five patients required a third operation. CONCLUSIONS: A small number of patients (1) continue to have persistent symptoms after carpal tunnel release because of incorrect diagnosis or incomplete release of the transverse carpal ligament; (2) develop recurrent symptoms caused by circumferential fibrosis; or (3) develop completely new symptoms, which usually implies iatrogenic injury to branches of the median nerve. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 22090246 TI - Foam pore size is a critical interface parameter of suction-based wound healing devices. AB - BACKGROUND: Suction-based wound healing devices with open-pore foam interfaces are widely used to treat complex tissue defects. The impact of changes in physicochemical parameters of the wound interfaces has not been investigated. METHODS: Full-thickness wounds in diabetic mice were treated with occlusive dressing or a suction device with a polyurethane foam interface varying in mean pore size diameter. Wound surface deformation on day 2 was measured on fixed tissues. Histologic cross-sections were analyzed for granulation tissue thickness (hematoxylin and eosin), myofibroblast density (alpha-smooth muscle actin), blood vessel density (platelet endothelial cell adhesion molecule-1), and cell proliferation (Ki67) on day 7. RESULTS: Polyurethane foam-induced wound surface deformation increased with polyurethane foam pore diameter: 15 percent (small pore size), 60 percent (medium pore size), and 150 percent (large pore size). The extent of wound strain correlated with granulation tissue thickness that increased 1.7-fold in small pore size foam-treated wounds, 2.5-fold in medium pore size foam-treated wounds, and 4.9-fold in large pore size foam-treated wounds (p < 0.05) compared with wounds treated with an occlusive dressing. All polyurethane foams increased the number of myofibroblasts over occlusive dressing, with maximal presence in large pore size foam-treated wounds compared with all other groups (p < 0.05). CONCLUSIONS: The pore size of the interface material of suction devices has a significant impact on the wound healing response. Larger pores increased wound surface strain, tissue growth, and transformation of contractile cells. Modification of the pore size is a powerful approach for meeting biological needs of specific wounds. PMID- 22090247 TI - What is the price to pay for a free fibula flap? A systematic review of donor site morbidity following free fibula flap surgery. AB - BACKGROUND: A number of donor-site morbidities following free fibula flap surgery, although usually minor and transient, have been documented. The primary aim of this systematic review was to identify the incidence of donor-site morbidity after free fibula flap surgery, to discuss the causes of these morbidities, and to identify the best methods of prevention and treatment available. METHODS: A systematic search of the English and Chinese literature was performed of the PubMed, MEDLINE, Cochrane Library, and Embase databases. The study selection process was adapted from the PRISMA statement, and 42 articles complied with the study inclusion criteria. RESULTS: Forty-two relevant articles were included in the final analysis. Regarding early donor-site morbidity, the weighted mean incidences were as follows: wound infection, 1.07 percent; wound dehiscence, 7.0 percent; wound necrosis, 7.3 percent; delayed wound healing, 17.4 percent; partial skin graft loss, 8.1 percent; and total skin graft loss, 4.7 percent. The weighted mean incidence of early wound morbidity in surgical wounds that were closed primarily was 9.9 percent, compared with skin graft closure at 19.0 percent. In late donor-site morbidities, the weighted mean incidences were as follows: chronic pain, 6.5 percent; considerable gait abnormality, 3.9 percent; ankle instability, 5.8 percent; limited range of motion in the ankle, 11.5 percent; reduced muscle strength, 4.0 percent; claw toe, 6.1 percent; dorsiflexion of the great toe, 3.6 percent; and sensory deficit, 6.95 percent. The mean American Orthopaedic Foot and Ankle Society score was 85.5 percent. CONCLUSION: One would expect to pay a low price for free fibula flap surgery with adequate surgical experience, refinements in surgical technique, and comprehensive postoperative care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. PMID- 22090248 TI - Hypertelorism correction: what happens with growth? Evaluation of a series of 95 surgical cases. AB - BACKGROUND: This report documents the authors' experience with 95 hypertelorism corrections performed since 1971. The authors note their findings regarding outcomes, preferred age at surgery, technique, and stability of results with growth. METHODS: Patients were classified into three groups: midline clefts (with or without nasal anomalies, Tessier 0 to 14); paramedian clefts (symmetric or asymmetric with or without nasal anomalies); and hypertelorism with craniosynostosis. The authors developed a hypertelorism index to measure longitudinal orbital position. RESULTS: A total of 70 box osteotomies were performed. Twelve of 95 patients had a bipartition. Six of 95 patients underwent a unilateral orbital box displacement or a three-wall mobilization, and seven of 95 had a medial wall osteotomy. Eighty patients were graded 1 to 4 using the Whitaker scale. Fifty-nine of 80 patients received a grade of 1, 15 patients received a grade of 2, five patients received a grade of three, four patients initially scored a 4, and three patients underwent reoperation and were rescored as 1. The authors developed a hypertelorism index to rate 28 patients with long term follow-up. None showed deterioration of results over the long term. The complication rate was 4 percent. CONCLUSION: The most interesting finding was that an initially good result in terms of orbital correction, whatever the severity, remains good with time, and facial balance improves after completion of growth. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 22090249 TI - Defining the ideal nasolabial angle. AB - BACKGROUND: The nasolabial angle is defined as the angle between the line drawn through the midpoint of the nostril aperture and a line drawn perpendicular to the Frankfurt horizontal while intersecting subnasale. An arbitrary range of 90 to 120 degrees for the nasolabial angle is usually stated in the literature. The purpose of this study was to objectively define the ideal nasolabial angle. METHODS: Life-sized, lateral photographs of 10 men and 10 women who had undergone rhinoplasty performed by the senior surgeon were selected. The photographs were electronically altered to change the nasolabial angle by 4 degrees. For men and women, these angles were 90, 94, 98, 102, 106, and 110 degrees. Sixteen raters, including plastic surgery attending staff, residents, and office staff, selected their most aesthetically pleasing nasolabial angle. RESULTS: Data analysis was done using the distribution of means of the first preference nasolabial angle values based on all 16 raters. The mean angle for ideal male nasolabial angle was 95.96 degrees +/- 2.57 degrees (mean +/- SD). The mean angle for women was 97.7 +/- 2.32 degrees. Based on these standard deviations, the ideal nasolabial angle would be 93.4 to 98.5 degrees for men and 95.5 to 100.1 degrees for women. CONCLUSIONS: The authors' results indicate a much closer range of nasolabial angle between men and women than previously reported in the literature. This study is the first of its type to objectively define the ideal aesthetic nasolabial angle. In addition, the ideal nasolabial angle for women was found to be less obtuse than previously thought. PMID- 22090250 TI - Reconstructive surgery training: increased operative volume in plastic surgery residency programs. AB - BACKGROUND: Practitioners in other surgical specialties have increasingly advanced their volume of reconstructive procedures traditionally served by plastic surgeons. Because there has not been a previous specialty training comparison, the average operative reconstructive volume of graduating plastic surgery residents was formally compared with that of other specialties. METHODS: The authors review the case log statistical reports of the Accreditation Council for Graduate Medical Education. For each specialty, this annual report highlights the average number of cases performed for all graduating residents. The national case log reports were reviewed for orthopedic surgery, otolaryngology, and plastic surgery. Six procedures were compared for residents graduating in the 2006 to 2010 academic years and are reviewed. A two-sample Welch-Satterthwaite t test for independent samples with heterogeneous variance was conducted to compare the average number of procedures performed per graduating resident. RESULTS: Graduates of plastic surgery residencies compared with graduates of other specialties performed more cleft lip and palate repairs, hand amputation, hand fracture, and nasal fracture procedures. This difference showed statistical significance for all years examined (2006 to 2010). For repair of mandible fractures, plastic surgery trainees had significantly more cases for 2006 to 2009 but not 2010. CONCLUSIONS: The quantitative operative experience of graduating plastic surgery residents for selected reconstructive cases is above that of the average graduating trainee outside of plastic surgery. Given the exposure and strength of plastic surgery training, plastic surgeons should remain at the forefront of reconstructive surgery. PMID- 22090251 TI - Migraine surgery practice patterns and attitudes. AB - BACKGROUND: Minimally invasive techniques have been developed to treat migraine headache, and several reports have shown efficacy in treating select patients who are refractory to conventional therapies. Although there is a growing body of evidence supporting migraine surgery, no study has examined its adoption by plastic surgeons in the United States. METHODS: A Web-based survey consisting of 17 ad hoc questions was designed to ascertain respondents' demographics, experience, knowledge, and attitudes regarding migraine surgery. After pilot testing, the survey was distributed by means of email to the entire membership of the American Society of Plastic Surgeons. RESULTS: A total of 3747 American Society of Plastic Surgeons members were surveyed, and 193 surveys were completed, for a response rate of 5.2 percent. Thirty-four respondents (18 percent) had performed surgery to treat migraine headache. Among those who have performed migraine surgery, over 80 percent reported improvement in patient symptoms. Of those who have not performed migraine surgery, 60 percent would be interested if an appropriate patient was referred to them by a neurologist. CONCLUSION: Although there is interest in migraine surgery among a subset of plastic surgeons, significant barriers to performing migraine surgery include deficient referral patterns from neurologists and lack of familiarity with the concept and techniques of migraine surgery. PMID- 22090252 TI - Additional benefits of reduction mammaplasty: a systematic review of the literature. AB - BACKGROUND: Reduction mammaplasty is commonly described with regard to its qualitative benefits. The authors sought to perform a systematic review of the literature focusing on functional outcomes after reduction mammaplasty with regard to physical and psychological symptom improvement, including weight related effects, exercise, and eating behaviors, in addition to aesthetic outcomes. METHODS: A systematic review of the English literature was performed using the PubMed database to evaluate outcomes following reduction mammaplasty from 1977 to 2010. Studies were chosen that addressed the physical and psychological benefits of reduction mammaplasty using a validated questionnaire. RESULTS: Women who undergo reduction mammaplasty have a functional improvement in musculoskeletal pain, headaches, sleep, and breathing. Psychological benefits are vast and include improved self-esteem, sexual function, and quality of life, in addition to less anxiety and depression. After reduction mammaplasty, women appear to exercise more and have a reduction in eating disorders. CONCLUSION: The authors present a comprehensive review of the literature with regard to the physical and emotional concerns women with macromastia experience and the broad benefits reduction mammaplasty could have for their daily functions and quality of life postoperatively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 22090253 TI - Identification of T-lymphocyte function in healthy vs. septic preterms and its relation to candidal infections in the hospital setting. AB - OBJECTIVES: To compare T-cell function in healthy/septic preterms in relation to healthy term babies. Also to determine correlation of sepsis severity with T-cell function and risk to candidal infection. METHODS: Patients were recruited to one of three groups. Group (I) included 30 healthy growing preterms, group (II) included preterms with neonatal sepsis whereas group (III) included 30 healthy full term neonates. Patients underwent history taking and comprehensive examination plus laboratory tests including T-Lymphocyte function by blastoid transformation method using phytohaemagglutinin (PHA). RESULTS: A significant difference exists between healthy preterm vs. septic newborn T cell counts and functions especially those with multiorgan system failure. No correlation was found between candidal infection and T cell functions. CONCLUSIONS: T cell functions are remarkably lower in septic newborns. Septic preterms may have low T cell functions despite absence of lymphopenia. Early detection is advised to improve outcome. PMID- 22090254 TI - Changing profile of severe malaria in north Indian children. AB - OBJECTIVE: To look for profile of severe malaria and contribution of vivax infection to malarial morbidity in North Indian children. METHODS: Detailed clinical, biochemical and hematological characteristics of children hospitalized with severe malaria over last 3 y were recorded. Presence of malarial parasite on peripheral smear and/or positive antigen test was considered as diagnostic for malaria. RESULTS: A total of 131(55.3%) patients with Plasmodium vivax (Pv), 79 (33.3%) with Plasmodium falciparum (Pf) and 27 (11.4%) with mixed infections were admitted. Cerebral malaria, severe anemia and shock were significantly more frequently observed in Pf group, while hepatic, renal, respiratory, and bleeding complications were more commonly seen in Pv patients. Malaria mortality was highest in mixed infection (11.1%), followed by Pf (7.6%) and Pv (3%) group. CONCLUSIONS: Severe and fatal vivax malaria is an emerging recognized entity and challenges the perception of Pv as a benign disease. Further clinical studies and molecular research is required to understand emergence of severe malaria in vivax mono-infection. PMID- 22090255 TI - Recombinant human IGF-1 (insulin-like growth factor) therapy: where do we stand today? AB - Recombinant human (rh) IGF-1 has been available for therapy since the 1980s and has been commercially available for over 5 y, yet the role of rhIGF-1 in treating children with short stature remains ambiguous. This is consequent to the inherent difficulty in defining criteria for IGF-1 deficiency, and in determining the outcome of rhIGF-1 therapy in terms of growth rate and adult height. The rationale for its efficacy compared with rhGH (recombinant human growth hormone) for treatment of short stature is still widely debated. Additionally, adverse events such as increased intracranial pressure and hypoglycemia are of therapeutic concern. The goal of this article is to review published data that describes the impact of IGF-1 therapy in treatment of short stature and other growth disorders. PMID- 22090256 TI - Copper accumulation, translocation, and toxic effects in grapevine cuttings. AB - PURPOSE: Although the ecotoxicological effects of copper (Cu) on grapevine are of global concern due to the intensive and long-term application of Cu-based fungicides in vineyards, comparatively little is known about the phytotoxicity, accumulation, and translocation of Cu in grapevines. Therefore, this study was to conduct a hydroponic experiment to determine the influence of solution Cu concentration not only on bioaccumulation and the translocation of Cu in grapevine roots, stems, and leaves, but also on the subsequent growth inhibition of the roots. METHODS: Grapevine cuttings were grown for 30 days and then exposed to various Cu concentrations (0.1-50 MUM) for 15 days. The dose-response profile was described by a sigmoid Hill equation. Optical microscopy was used to examine the cytotoxicity of Cu on the roots. In addition, bioaccumulation factors (BAFs) and translocation factors (TFs) were calculated from the results of the hydroponic experiment. RESULTS: Copper was tolerated by grapevines at a concentration <=1 MUM. The median inhibition concentration (IC(50)) obtained from the Hill model was 3.94 MUM (95% confidence interval, 3.65-4.24). From the light micrographs of root tip cells, signs of toxicity including increased vacuolization and plasmolysis were observed at solution Cu concentrations >=10 MUM. In addition, a higher Cu concentration was found in the roots (25-12,000 mg kg(-1)) than in the stems (5-540 mg kg(-1)) and leaves (7-46 mg kg(-1)), indicating a very limited translocation of Cu from the roots to the aboveground parts. CONCLUSIONS: This study investigated not only the macroscopic root growth and Cu accumulation by grapevine, but also the microscopic changes in root tissue at the cell level after the exposure experiment. Based on the BAFs and TFs, the grapevine could be considered a Cu-exclusive plant. For toxic effects on the exposure of roots to Cu, this study also revealed that root growth, as well as the histological changes in rhizodermal cells, can be used as phytotoxic indicators of grapevine under Cu stress. PMID- 22090257 TI - Mercury policy and regulations for coal-fired power plants. AB - INTRODUCTION: Mercury is a high-priority regulatory concern because of its persistence and bioaccumulation in the environment and evidence of its having serious adverse effects on the neurological development of children. DISCUSSION: Mercury is released into the atmosphere from both natural and anthropogenic sources. Coal-fired utilities are considered to be one of the largest anthropogenic mercury emission sources. The period since the late 1990s has been marked by increasing concern over mercury emissions from combustion systems to the extent that a number of national governments have either already implemented or are in the process of implementing, legislation aimed at enforcing tighter control over mercury emissions and a reduction in mercury consumption. CONCLUSION: This review examines the most important national and international policies and agreements for controlling mercury emissions from coal-fired combustion systems. To provide a global perspective, this study lists the countries with the largest estimated mercury emissions and regulatory efforts to reduce them. PMID- 22090258 TI - An update on monoclonal gammopathy and neuropathy. AB - Peripheral neuropathy associated with monoclonal gammopathy is a rare but important cause of neuropathy that can herald serious underlying disease. IgM monoclonal gammopathy of undetermined significance (MGUS) is the most commonly found monoclonal gammopathy associated with neuropathy, with characteristic clinical, electrophysiologic, and pathologic features. The IgG and IgA monoclonal gammopathies are rarely associated with specific neuropathies. Standard immunomodulatory agents including steroids, intravenous immunoglobulin, and plasmapheresis have shown limited efficacy in IgM MGUS. Neuropathies associated with specific lymphoproliferative disorders may not respond to treatments aimed at that disorder. Case series had shown promising results with rituximab, a monoclonal antibody that targets the B cell surface antigen CD20 and results in a rapid and sustained depletion of B cells; however, two recent randomized controlled trials with rituximab failed to provide evidence of efficacy in primary outcome measures, despite reduction in antibody levels. Long-term studies looking at the association between specific immunologic markers and disease recurrence are needed to ultimately develop targeted therapies. PMID- 22090259 TI - Extinction of goal tracking also eliminates the conditioned reinforcing effects of an appetitive conditioned stimulus. AB - Previous studies have suggested that the effects of extinction are response specific. The present study investigated whether an extinction treatment that eliminated goal tracking elicited by an appetitive conditioned stimulus (CS) would also eliminate the conditioned reinforcing effects of that CS. Rats were first trained on a goal-tracking procedure in which an auditory CS was paired with a food unconditioned stimulus. Animals learned to approach the location where the food was delivered. In a subsequent phase, rats in one group received extinction training that eliminated the goal-tracking elicited by the CS. Rats in the other group did not experience extinction of the food-paired CS. Then, both groups received a test for conditioned reinforcement in which leverpresses resulted in the brief presentation of the stimulus previously paired with food. This stimulus did not act as a conditioned reinforcer in the group that had been subjected to extinction training, but did serve as a conditioned reinforcer in the group that did not experience extinction. These results indicate that the effects of extinction generalize from the approach-eliciting to the conditioned reinforcing effects of an appetitive CS. PMID- 22090260 TI - Posterior reversible encephalopathy syndrome induced by anti-VEGF agents. AB - Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity that may occur in patients receiving anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab and tyrosine kinase inhibitors. Little is known about the characteristics of patients at risk for PRES under anti-VEGF agents. We carried out a comprehensive review of reports documenting the occurrence of PRES in patients receiving anti-VEGF agents. Twenty-six patients are described with a majority of females (73.1%). Almost a third of patients had a past history of hypertension. The most common symptoms included headache, visual disturbance and seizure. A vast majority of patients had hypertension at the diagnosis of PRES, and proteinuria was detectable each time it was investigated. Neurological outcome was favorable in all cases with a symptomatic treatment including blood pressure control. The risk of PRES is increased when blood pressure is poorly controlled and when proteinuria is detectable. The clinical course appears favorable with a symptomatic treatment. PRES is a potentially severe but manageable toxicity of anti-VEGF agents. PMID- 22090261 TI - Automated assembly of optimally spaced and balanced paired comparisons: controlling order effects. AB - To control order effects in questionnaires containing paired comparisons, Ross (1934) described an optimal ordering of the pairings. The pairs can also be balanced so that every stimulus appears equal numbers of times as the first and the second member of a pair. First, we describe and illustrate the optimally spaced, balanced ordering of pairings. Then we show how the optimally spaced, balanced order can be used to implement a matrix-sampling design or a fully incomplete design when the number of stimuli n is so large that respondents cannot reasonably be expected to judge all n(n - 1)/2 pairs. The algorithm for balancing and optimally spacing the list of pairs is described. PMID- 22090262 TI - A prospective study of psychological distress and weight status in adolescents/young adults. AB - BACKGROUND: The obesity-psychological distress relationship remains controversial. PURPOSE: This study aims to assess whether adolescents' psychological distress was associated with body mass index (BMI) class membership determined by latent class analysis. METHODS: Distress (anxiety, depression) and BMI were measured annually for 4 years in 1,528 adolescents. Growth mixture modeling derived latent BMI trajectory classes for models with 2-11 classes. The relationship of distress to class membership was examined in the best-fitting model using vector generalized linear regression. RESULTS: BMI trajectories were basically flat. The five-class model [normal weight (48.8%), overweight (36.7%), obese who become overweight (3.7%), obese (9.4%), and severely obese (1.3%)] was the preferred model (Bayesian information criterion = 22789.2, df = 31; rho = 0.84). Greater distress was associated with higher baseline BMI and, therefore, class membership. CONCLUSIONS: Psychological distress is associated with higher BMI class during adolescence. To determine whether distress "leads" to greater weight gain may require studies of younger populations. PMID- 22090263 TI - Epidural steroid injections. AB - Epidural steroid injection (ESI) is the most commonly performed intervention in pain clinics across the United States. This article provides an evidence-based review of ESI, including data on efficacy, patient selection, comparison of types, and complications. The data strongly suggest that ESI can provide short term relief for radicular symptoms but are less compelling for long-term effects or relief of back pain. Although it has been asserted that transforaminal ESIs are more efficacious than interlaminar injections, the evidence supporting this is limited. PMID- 22090264 TI - Radiofrequency treatment of facet-related pain: evidence and controversies. AB - Pain originating from the lumbar facet joints is estimated to represent about 15% of all low back pain complaints. The diagnostic block is considered to be a valuable tool for confirming facetogenic pain. It was demonstrated that a block of the ramus medialis of the ramus dorsalis is preferred over an intra-articular injection. The outcome of the consequent radiofrequency treatment is not different in patients reporting over 80% pain relief after the diagnostic block than in those who have between 50% and 79% pain relief. There is one well conducted comparative trial assessing the value of one or two controlled diagnostic blocks to none. The results of the seven randomized trials on the use of radiofrequency treatment of facet joint pain demonstrate that good patient selection is imperative for good clinical outcome. Therefore, we suggest one block of the ramus medialis of the ramus dorsalis before radiofrequency treatment. PMID- 22090265 TI - Central hypothyroidism in a patient with pituitary autoimmunity: evidence for TSH independent thyroid hormone synthesis. AB - CONTEXT: Acquired central hypothyroidism is rare, especially when isolated, and is typically associated with detectable, although biologically inactive, serum TSH. OBJECTIVE: We describe a 56-yr-old woman with profound central hypothyroidism and partial central hypoadrenalism, in the absence of other endocrine abnormalities. In contrast to most cases of central hypothyroidism, serum TSH remained undetectable for 9 months before the initiation of thyroid hormone and hydrocortisone treatment. A test for pituitary autoantibody was moderately positive. Serum free T(4), serum T(3), and neck radioiodine uptake were low but detectable. The thyroid and pituitary glands appeared morphologically normal on neck ultrasound and head magnetic resonance imaging, respectively. SETTINGS: The study was conducted in a tertiary academic medical center. CONCLUSIONS: This case illustrates the variable clinical presentation of pituitary autoimmunity. The persistence of low but detectable thyroid hormone levels and radioiodine neck uptake in the absence of TSH suggests that significant TSH-independent thyroid hormone synthesis may occur in the normal thyroid. PMID- 22090266 TI - Higher rates of bone loss in postmenopausal HIV-infected women: a longitudinal study. AB - CONTEXT AND OBJECTIVE: The objective of the study was to assess the effects of HIV infection and antiretroviral therapy on change in bone mineral density (BMD) in postmenopausal minority women. DESIGN, SETTING, AND PATIENTS: We report a longitudinal analysis of change in BMD with a median duration of 15.4 (interquartile range 13.1, 20.7) months in a prospective cohort study of 128 (73 HIV+, 55 HIV-) postmenopausal Hispanic and African-American women. MAIN OUTCOME MEASURES: Annualized change in BMD by dual-energy x-ray absorptiometry and correlation with baseline markers of bone turnover and serum levels of inflammatory cytokines were measured. RESULTS: HIV+ women were younger (56 +/- 1 vs. 59 +/- 1 yr, P < 0.05) and had lower body mass index (BMI; 28 +/- 1 vs. 31 +/ 1 kg/m(2), P < 0.01). The majority of HIV+ women were on established antiretroviral therapy for more than 3 yr. At baseline, BMD, adjusted for age, race, and BMI, was lower in HIV+ women at the lumbar spine (LS), total hip, and radius and serum C-telopeptide was higher. Annualized rates of bone loss adjusted for baseline BMD were higher in HIV+ women by 2.4-fold at the LS (-1.2 +/- 0.3% vs. -0.5 +/- 0.3%, P = 0.0009), 3.7-fold at the one third radius (-1.1 +/- 0.2% vs. -0.3 +/- 0.2, P = 0.006) and 1.7-fold at the ultradistal radius (-1.2 +/- 0.2% vs. -0.7 +/- 0.2%, P = 0.02). In multivariate analysis, HIV+ status predicted bone loss at the LS, total hip, and ultradistal radius. Among HIV+ women, lower BMI, higher markers of bone turnover levels, and tenofovir were associated with more bone loss. CONCLUSION: HIV+ postmenopausal minority women had lower BMD, increased bone turnover, and higher rates of bone loss than HIV- women. These features may place these women at increased risk for fracture as they age. PMID- 22090267 TI - Permanent hypopituitarism is rare after structural traumatic brain injury in early childhood. AB - BACKGROUND: We sought to determine the incidence of permanent hypopituitarism in a potentially high-risk group: young children after structural traumatic brain injury (TBI). METHODS: We conducted a cross-sectional study with longitudinal follow-up. Dynamic tests of pituitary function (GH and ACTH) were performed in all subjects and potential abnormalities critically evaluated. Puberty was clinically staged; baseline thyroid function, prolactin, IGF-I, serum sodium, and osmolality were compared with age-matched data. Diagnosis of GH deficiency was based on an integrated assessment of stimulated GH peak (<5 MUg/liter suggestive of deficiency), IGF-I, and growth pattern. ACTH deficiency was diagnosed based on a subnormal response to two serial Synacthen tests (peak cortisol <500 nmol/liter) and a metyrapone test. RESULTS: We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 +/- 1.5 yr) 6.5 +/- 3.2 yr after injury. Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental. Two participants had developed precocious puberty, which is within the expected background population rate. Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth. Stimulated peak cortisol was low in 17 (8%), but all had normal ACTH function on follow-up. One participant had a transient low serum T(4). Therefore, no cases of hypopituitarism were recorded. CONCLUSION: Permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. Precocious puberty was the only pituitary hormone abnormality found, but the prevalence did not exceed that of the normal population. PMID- 22090268 TI - Synthetic human parathyroid hormone 1-34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. AB - CONTEXT: Vitamin D therapy for hypoparathyroidism does not restore PTH-dependent renal calcium reabsorption, which can lead to renal damage. An alternative approach, PTH 1-34 administered twice daily, provides acceptable long-term treatment but is associated with nonphysiological serum calcium fluctuation. OBJECTIVE: Our objective was to compare continuous PTH 1-34 delivery, by insulin pump, with twice-daily delivery. RESEARCH DESIGN AND METHODS: In a 6-month, open label, randomized, crossover trial, PTH 1-34 was delivered by pump or twice-daily sc injection. After each 3-month study period, serum and 24-h urine mineral levels and bone turnover markers were measured daily for 3 d, and 24-h biochemical profiles were determined for serum minerals and 1,25-dihydroxyvitamin D(3) and for urine minerals and cAMP. STUDY PARTICIPANTS AND SETTING: Eight patients with postsurgical hypoparathyroidism (mean +/- sd age 46 +/- 5.6 yr) participated at a tertiary care referral center. RESULTS: Pump vs. twice-daily delivery of PTH 1-34 produced less fluctuation in serum calcium, a more than 50% reduction in urine calcium (P = 0.002), and a 65% reduction in the PTH dose to maintain eucalcemia (P < 0.001). Pump delivery also produced higher serum magnesium level (P = 0.02), normal urine magnesium, and reduced need for magnesium supplements. Finally, pump delivery normalized bone turnover markers and significantly lowered urinary cross-linked N-telopeptide of type 1 collagen and pyridinium crosslinks compared with twice-daily injections (P < 0.05). CONCLUSION: Pump delivery of PTH 1-34 provides the closest approach to date to physiological replacement therapy for hypoparathyroidism. PMID- 22090269 TI - Glycemic control in non-critically ill hospitalized patients: a systematic review and meta-analysis. AB - BACKGROUND: The effect of intensive therapy to achieve tight glycemic control in patients hospitalized in non-critical care settings is unclear. METHODS: We conducted a systematic review and meta-analysis to determine the effect of intensive glycemic control strategies on the outcomes of death, stroke, myocardial infarction, incidence of infection, and hypoglycemia. We included randomized and observational studies. Bibliographic databases were searched through February 2010. Random effects model was used to pool results across studies. RESULTS: Nineteen studies (nine randomized and 10 observational studies) were included. The risk of bias across studies was moderate. Meta-analysis demonstrates that intensive glycemic control was not associated with significant effect on the risk of death, myocardial infarction, or stroke. There was a trend for increased risk of hypoglycemia (relative risk, 1.58; 95% confidence interval, 0.97-2.57), particularly in surgical studies and when the planned glycemic target was achieved. Intensive glycemic control was associated with decreased risk of infection (relative risk, 0.41; 95% confidence interval, 0.21-0.77) that was mainly derived from studies in surgical settings. CONCLUSION: Intensive control of hyperglycemia in patients hospitalized in non-critical care settings may reduce the risk of infection. The quality of evidence is low and mainly driven by studies in surgical settings. PMID- 22090270 TI - Quality of life in European patients with Addison's disease: validity of the disease-specific questionnaire AddiQoL. AB - CONTEXT: Patients with Addison's disease (AD) self-report impairment in specific dimensions on well-being questionnaires. An AD-specific quality-of-life questionnaire (AddiQoL) was developed to aid evaluation of patients. OBJECTIVE: We aimed to translate and determine construct validity, reliability, and concurrent validity of the AddiQoL questionnaire. METHODS: After translation, the final versions were tested in AD patients from Norway (n = 107), Sweden (n = 101), Italy (n = 165), Germany (n = 200), and Poland (n = 50). Construct validity was examined by exploratory factor analysis and Rasch analysis, aiming at unidimensionality and fit to the Rasch model. Reliability was determined by Cronbach's coefficient-alpha and Person separation index. Longitudinal reliability was tested by differential item functioning in stable patient subgroups. Concurrent validity was examined in Norwegian (n = 101) and Swedish (n = 107) patients. RESULTS: Exploratory factor analysis and Rasch analysis identified six items with poor psychometric properties. The 30 remaining items fitted the Rasch model and proved unidimensional, supported by appropriate item and person fit residuals and a nonsignificant chi(2) probability. Crohnbach's alpha-coefficient 0.93 and Person separation index 0.86 indicate high reliability. Longitudinal reliability was excellent. Correlation with Short Form 36 and Psychological General Well-Being Index scores was high. A shorter subscale comprising eight items also proved valid and reliable. Testing of AddiQoL-30 in this large patient cohort showed significantly worse scores with increasing age and in women compared with men but no difference between patients with isolated AD and those with concomitant diseases. CONCLUSION: The validation process resulted in a revised 30-item AddiQoL questionnaire and an eight-item AddiQoL short version with good psychometric properties and high reliability. PMID- 22090271 TI - The Akt inhibitor MK2206 synergizes, but perifosine antagonizes, the BRAF(V600E) inhibitor PLX4032 and the MEK1/2 inhibitor AZD6244 in the inhibition of thyroid cancer cells. AB - PURPOSE: The purpose of the study was to explore optimal combinations of currently actively developed drugs for dually targeting the Ras -> Raf -> MAPK kinase (MEK) -> MAPK/ERK (MAPK) and the phosphatidylinositol 3-kinase/Akt pathways as effective treatments for thyroid cancer. EXPERIMENTAL DESIGN: We tested the combinations of the Akt inhibitors MK2206 or perifosine with the BRAF(V600E) inhibitor PLX4032 or the MEK1/2 inhibitor AZD6244 in thyroid cancer cells harboring both the BRAF(V600E) and PIK3CA mutations. RESULTS: We found that MK2206 could potently, when used alone, and synergistically, when combined with either PLX4032 or AZD6244, inhibit thyroid cancer cell growth with all the combination index values lower than 1. Perifosine could potently inhibit thyroid cancer cell growth when used alone, but a strong antagonism occurred between this drug and PLX4032 or AZD6244 in the inhibition of thyroid cancer cell growth with all combination index values higher than 1. Combinations of MK2206 with PLX4032 or AZD6244 dramatically enhanced G1 cell cycle arrest induced by each drug alone. However, G2 cell cycle arrest uniquely induced by perifosine alone and G1 cell cycle arrest induced by PLX4032 or AZD6244 were both reversed by combination treatments, providing a mechanism for their antagonism. All these drugs could correspondingly inhibit the MAPK and phosphatidylinositol 3-kinase/Akt signalings, confirming their expected target effects. CONCLUSIONS: We demonstrated, unexpectedly, opposite outcomes of MK2206 and perifosine in their combinational treatments with BRAF(V600E)/MEK inhibitors in thyroid cancer cells. The data may help appropriate selection of these prominent drugs for clinical trials of combination therapies for thyroid cancer. PMID- 22090273 TI - Overexpression of metallothionein I/II: a new feature of thyroid follicular cells in Graves' disease. AB - CONTEXT: One salient feature of autoimmune thyroid disease is the inappropriate expression of human leukocyte antigen (HLA) class II molecules by thyroid follicular cells. Metallothioneins (MT) are small proteins induced by tissue stress that can contribute to restoring homeostasis of tissue inflammation and have been found to be increased in a transcriptomic analysis of Graves' disease (GD) glands. METHODOLOGY: To assess the role of MT in the pathogenesis of GD, we analyzed MT-I and -II expression and distribution in GD-affected thyroid glands (n = 14) compared with other thyroid diseases (n = 20) and normal thyroid glands (n = 5). Two-color indirect immunofluorescence and semiquantitative morphometry were applied. The relationship between MT and HLA class II expression was analyzed by their degree of colocalization in GD sections, and in vitro induction kinetics and expression of these molecules on the HT93 thyroid cell line were compared by quantitative RT-PCR and flow cytometry using interferon-gamma and zinc as stimuli. RESULTS: MT were clearly overexpressed in nine of 14 GD glands. MT expression distribution in GD was almost reciprocal to that of HLA class II. In vitro analysis of MT and HLA class II demonstrated that MT is induced more slowly and at a lower level than HLA. Moreover, the main MT inducer, zinc, reduces interferon-gamma-induced class II expression. CONCLUSIONS: These findings show that MT and HLA class II play very different roles in the autoimmune process by affecting the thyroid gland, thereby pointing to the possible role of MT as a marker of cell stress and homeostasis restoration in GD. PMID- 22090272 TI - Satisfaction with genital surgery and sexual life of adults with XY disorders of sex development: results from the German clinical evaluation study. AB - BACKGROUND: Prenatal deficit of androgens or androgen action results in atypical genitalia in individuals with XY disorders of sex development (XY,DSD). XY,DSD include mainly disorders of gonadal development and testosterone synthesis and action. Previously, most XY,DSD individuals were assigned to the female sex. Constructive genital surgery allowing heterosexual intercourse, gonadectomy, and hormone therapy for feminization were often performed. However, outcome studies are scarce. OBJECTIVE: Our objective was evaluation of satisfaction with genital surgery and sexual life in adults with XY,DSD. DESIGN AND METHODS: We evaluated 57 individuals with XY,DSD from the German multicenter clinical evaluation study with a condition-specific questionnaire. The individuals were divided into subgroups reflecting the absence/presence of partial androgen effect or genital constructive surgery. RESULTS: Dissatisfaction with function of the surgical result (47.1%) and clitoral arousal (47.4%) was high in XY,DSD partially androgenized females after feminization surgery. Dissatisfaction with overall sex life (37.5%) and sexual anxieties (44.2%) were substantial in all XY,DSD individuals. Problems with desire (70.6%), arousal (52.9%), and dyspareunia (56.3%) were significant in XY,DSD complete females. 46,XY partially androgenized females reported significantly more often partners of female (9.1%) or both sexes (18.2%) and dyspareunia (56.5%) compared with controls. Individuals with complete androgen insensitivity syndrome stated significant problems with desire (81.8%), arousal (63.6%), and dyspareunia (70%). CONCLUSIONS: Care should be improved in XY,DSD patients. Constructive genital surgery should be minimized and performed mainly in adolescence or adulthood with the patients' consent. Individuals with DSD and their families should be informed with sensibility about the condition. Multidisciplinary care with psychological and nonprofessional support (parents, peers, and patients' support groups) is mandatory from child to adulthood. PMID- 22090274 TI - Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome. AB - CONTEXT: The lipodystrophies (LD) are characterized by metabolic abnormalities (insulin resistance, hypertriglyceridemia, and diabetes) and a polycystic ovarian syndrome (PCOS) phenotype. Therapeutic administration of leptin improves insulin sensitivity and the metabolic features. OBJECTIVE: The objective of the study was to investigate whether the PCOS features are corrected by increasing insulin sensitivity as a function of leptin treatment. DESIGN: This was a prospective, open-label trial using leptin replacement in various forms of lipodystrophy. SETTING: The study was performed at the Clinical Center at the National Institutes of Health. PATIENTS OR OTHER PARTICIPANTS: Twenty-three female patients with LD were enrolled in a leptin replacement trial from 2000 to the present. Different parameters were assessed at baseline and after 1 yr of therapy. INTERVENTION(S): Patients were treated with leptin for at least 1 yr. MAIN OUTCOME MEASURE(S): We evaluated free testosterone, SHBG, and IGF-I at baseline and after 1 yr of leptin. RESULTS: Testosterone levels decreased from 3.05 +/-0.6 ng/ml at baseline to 1.7 +/-0.3 ng/ml (P = 0.02). SHBG increased from 14.5 +/-2 to 25 +/-3.5 nmol/liter after 1 yr of leptin therapy. There were no significant changes in the levels of gonadotropins and ovarian size as a result of leptin replacement therapy. IGF-I increased significantly after leptin therapy from 150 +/-14 to 195 +/-17. There was a significant decrease in triglycerides and glycosylated hemoglobin in the context of reduced insulin requirements. CONCLUSIONS: In the present study, we show that LD may be a model for the common forms of PCOS and that the endocrine features are corrected by leptin therapy, which reduces insulin resistance. PMID- 22090275 TI - LCAT, HDL cholesterol and ischemic cardiovascular disease: a Mendelian randomization study of HDL cholesterol in 54,500 individuals. AB - BACKGROUND: Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear. METHODS: We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants in the Copenhagen General Population Study (CGPS), of which 991 and 1,693 participants, respectively, had developed myocardial infarction (MI) by August 2010. Participants in the CCHS were genotyped for all six variants identified by resequencing lecithin-cholesterol acyltransferase in 380 individuals. One variant, S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis. RESULTS: Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies combined was 0.49 (0.11-2.16), whereas the hazard ratio for MI for a 50% reduction in plasma HDL cholesterol in the CCHS was 2.11 (1.70-2.62) (P(comparison) = 0.03). CONCLUSION: Low plasma HDL cholesterol levels robustly associated with increased risk of MI but genetically decreased HDL cholesterol did not. This may suggest that low HDL cholesterol levels per se do not cause MI. PMID- 22090276 TI - Menin missense mutants encoded by the MEN1 gene that are targeted to the proteasome: restoration of expression and activity by CHIP siRNA. AB - CONTEXT: In multiple endocrine neoplasia type 1 (MEN1) characterized by tumors of parathyroid, enteropancreas, and anterior pituitary, missense mutations in the MEN1 gene product, menin, occur in a subset of cases. The mutant proteins are degraded by the proteasome. However, whether their expression and activity can be restored is not known. OBJECTIVE: Our objective was to functionally characterize a panel of 16 menin missense mutants, including W423R and S443Y identified in new MEN1 families, with respect to protein stability, targeting to the proteasome and restoration of expression by proteasome inhibitors and expression and function by small interfering RNA technology. METHODS: Flag-tagged wild-type (WT) and missense menin mutant expression vectors were transiently transfected in human embryonic kidney (HEK293) and/or rat insulinoma (Rin-5F) cells. RESULTS: The majority of mutants were short-lived, whereas WT menin was stable. Proteasome inhibitors MG132 and PS-341 and inhibition of the chaperone, heat-shock protein 70 (Hsp70), or the ubiquitin ligase, COOH terminus of Hsp70-interacting protein (CHIP), by specific small interfering RNA, restored the levels of the mutants, whereas that of WT menin was largely unaffected. Inhibition of CHIP restored the ability of mutants to mediate normal functions of menin: TGF-beta up-regulation of the promoters of its target genes, the cyclin-dependent kinase inhibitors p15 and p21 as well as TGF-beta inhibition of cell numbers. CONCLUSION: When the levels of missense menin mutants that are targeted to the proteasome are normalized they may function similarly to WT menin. Potentially, targeting specific components of the proteasome chaperone pathway could be beneficial in treating a subset of MEN1 cases. PMID- 22090277 TI - Urinary bisphenol A (BPA) concentration associates with obesity and insulin resistance. AB - CONTEXT: Bisphenol A (BPA) is one of the world's highest-volume chemicals in use today. Previous studies have suggested BPA disturbs body weight regulation and promotes obesity and insulin resistance. But epidemiological data in humans were limited. OBJECTIVE: Our objective was to determine whether BPA associates with obesity and insulin resistance. DESIGN, SETTING, AND PARTICIPANTS: This cross sectional study included 3390 adults aged 40 yr or older, in Songnan Community, Baoshan District, Shanghai, China. MAIN OUTCOME MEASURES: Questionnaire, clinical and biochemical measurements, and urinary BPA concentration were determined. Generalized overweight was defined as body mass index (BMI) of 24 to less than 28 kg/m(2) and obesity was defined as BMI of 28 kg/m(2) or higher. Abdominal obesity was defined as waist circumference at least 90 cm for men and at least 85 cm for women. Insulin resistance was defined as the index of homeostasis model assessment of insulin resistance higher than 2.50. RESULTS: The participants in the highest quartile of BPA had the highest prevalence of generalized obesity [odds ratio (OR) = 1.50; 95% confidence interval (CI) = 1.15-1.97], abdominal obesity (OR = 1.28; 95% CI = 1.03-1.60), and insulin resistance (OR = 1.37; 95% CI = 1.06-1.77). In participants with BMI under 24 kg/m(2), compared with the lowest quartile, the highest quartile of BPA increased the prevalence of insulin resistance by 94% (OR = 1.94; 95% CI = 1.20-3.14), but this association was not observed in those with BMI of 24 kg/m(2) or higher. CONCLUSIONS: BPA was positively associated with generalized obesity, abdominal obesity, and insulin resistance in middle-aged and elderly Chinese adults. PMID- 22090278 TI - Defects in GLP-1 response to an oral challenge do not play a significant role in the pathogenesis of prediabetes. AB - CONTEXT: There has been much speculation as to whether defects in glucagon-like peptide-1 (GLP-1) secretion play a role in the pathogenesis of type 2 diabetes and the progression from normal glucose tolerance to prediabetes and diabetes. OBJECTIVE: Our objective was to determine whether fasting and postchallenge concentrations of active and total GLP-1 decrease as glucose tolerance and insulin secretion worsen across the spectrum of prediabetes. DESIGN: This was a cross-sectional study. SETTING: The study was performed in the clinical research unit of an academic medical center. PARTICIPANTS: Participants included 165 subjects with a fasting glucose below 7.0 mmol/liter and not taking medications known to affect gastrointestinal motility or glucose metabolism. INTERVENTION: Intervention included a 2-h, 75-g oral glucose tolerance test with insulin, C peptide, glucagon, and GLP-1 measurements at seven time points. MAIN OUTCOME MEASURE: We evaluated the association of integrated, incremental active, and total GLP-1 concentrations with integrated, incremental glucose response to 75 g oral glucose. RESULTS: After accounting for covariates, there was no evidence of a relationship of incremental glucose concentrations after oral glucose tolerance test with active and total GLP-1 (r(s) = -0.16 and P = 0.14, and r(s) = 0.00 and P > 0.9, respectively). There also was no association of GLP-1 concentrations with insulin secretion and action. CONCLUSIONS: The lack of association of GLP-1 concentrations with glucose tolerance status and with insulin secretion and action in a cohort encompassing the full spectrum of prediabetes strongly argues against a significant contribution of defects in GLP-1 secretion to the pathogenesis of prediabetes. PMID- 22090279 TI - Baseline sympathetic nervous system activity predicts dietary weight loss in obese metabolic syndrome subjects. AB - CONTEXT: The sympathetic nervous system is an important physiological modulator of basal and postprandial energy expenditure. OBJECTIVE: Our objective was to investigate whether the variability of weight loss attained during hypocaloric dietary intervention is related to individual differences in baseline sympathetic drive and nutritional sympathetic nervous system responsiveness. PARTICIPANTS AND METHODS: Untreated obese subjects (n = 42; body mass index = 32.1 +/- 0.5 kg/m(2)), aged 57 +/- 1 yr, who fulfilled Adult Treatment Panel III metabolic syndrome criteria participated in a 12-wk weight loss program using a modified Dietary Approaches to Treat Hypertension (DASH) diet. Muscle sympathetic nerve activity (MSNA) was measured by microneurography at rest and in a subset of subjects during a standard 75-g oral glucose tolerance test. RESULTS: Weight loss (6.7 +/- 0.5 kg) was independently predicted by baseline resting MSNA burst incidence (r = 0.38; P = 0.019), which accounted for 14.3% of the variance after adjustment for age and baseline body weight. Weight loss-resistant subjects in the lower tertile of weight loss (4.4 +/- 0.3%) had significantly blunted MSNA responses to oral glucose at baseline compared with successful weight losers (9.6 +/- 0.8%). Absolute Delta MSNA averaged -7 +/- 2, -6 +/- 5, and -3 +/- 3 bursts per 100 heartbeats at 30, 60, and 90 min after glucose in the weight loss resistant group. Corresponding values in the successful weight loss group were 9 +/- 3, 12 +/- 3, and 15 +/- 4 bursts per 100 heartbeats (time * group interaction, P = 0.004). CONCLUSIONS: These findings indicate that baseline sympathetic drive and nutritional sympathetic responsiveness may be important prognostic biological markers for weight loss outcome. PMID- 22090280 TI - Diurnal rhythm of circulating nicotinamide phosphoribosyltransferase (Nampt/visfatin/PBEF): impact of sleep loss and relation to glucose metabolism. AB - CONTEXT: Animal studies indicate that nicotinamide phosphoribosyltransferase [Nampt/visfatin/pre-B-cell colony-enhancing factor (PBEF)] contributes to the circadian fine-tuning of metabolic turnover. However, it is unknown whether circulating Nampt concentrations, which are elevated in type 2 diabetes and obesity, display a diurnal rhythm in humans. OBJECTIVE: Our objective was to examine the 24-h profile of serum Nampt in humans under conditions of sleep and sleep deprivation and relate the Nampt pattern to morning postprandial glucose metabolism. INTERVENTION: Fourteen healthy men participated in two 24-h sessions starting at 1800 h, including either regular 8-h-night sleep or continuous wakefulness. Serum Nampt and leptin were measured in 1.5- to 3-h intervals. In the morning, plasma glucose and serum insulin responses to standardized breakfast intake were determined. MAIN OUTCOME MEASURES: Under regular sleep-wake conditions, Nampt levels displayed a pronounced diurnal rhythm, peaking during early afternoon (P < 0.001) that was inverse to leptin profiles peaking in the early night. When subjects stayed awake, the Nampt rhythm was preserved but phase advanced by about 2 h (P < 0.05). Two-hour postprandial plasma glucose concentrations were elevated after sleep loss (P < 0.05), whereas serum insulin was not affected. The relative glucose increase due to sleep loss displayed a positive association with the magnitude of the Nampt phase shift (r = 0.54; P < 0.05). CONCLUSIONS: Serum Nampt concentrations follow a diurnal rhythm, peaking in the afternoon. Sleep loss induces a Nampt rhythm phase shift that is positively related to the impairment of postprandial glucose metabolism due to sleep deprivation, suggesting a regulatory impact of Nampt rhythmicity on glucose homeostasis. PMID- 22090281 TI - Phospholipid transfer protein in the placental endothelium is affected by gestational diabetes mellitus. AB - CONTEXT: Gestational diabetes mellitus (GDM) causes alterations in fetal high density lipoproteins (HDL). Because phospholipid transfer protein (PLTP) is important for HDL (re)assembly and is expressed in the human placenta, we hypothesized that circulating fetal and/or placental PLTP expression and activity are altered in GDM. DESIGN: PLTP levels and activity were determined in maternal and fetal sera from GDM and controls. Placental PLTP was immunolocalized, and its expression was measured in placental tissue. PLTP regulation by glucose/insulin was studied in human endothelial cells isolated from placental vessels (HPEC). RESULTS: Placental Pltp expression was up-regulated in GDM (1.8-fold, P < 0.05). PLTP protein (5-fold, P < 0.01) and activity (1.4- to 2.5-fold) were higher in fetal than in maternal serum. The placental endothelium was identified as a major PLTP location. Insulin treatment of HPEC significantly increased secreted PLTP levels and activity. In GDM, fetal cholesterol, HDL-triglycerides and phospholipids were elevated compared with controls. Fetal PLTP activity was higher than maternal but unaltered in GDM. CONCLUSION: HPEC contribute to the release of active PLTP into the fetal circulation. Pltp expression is increased in GDM with hyperglycemia and/or hyperinsulinemia contributing. High PLTP activity in fetal serum may enhance conversion of HDL into cholesterol-accepting particles, thereby increasing maternal-fetal cholesterol transfer. PMID- 22090282 TI - Mifepristone effects on tumor somatostatin receptor expression in two patients with Cushing's syndrome due to ectopic adrenocorticotropin secretion. AB - CONTEXT: Two patients presented with Cushing's syndrome due to ectopic ACTH secretion. Initial localization studies included computed tomography, magnetic resonance imaging, and octreoscans ((111)In-pentreotide scintigraphy), which were negative in both patients. They were treated with the glucocorticoid receptor antagonist mifepristone, with improvement in their clinical symptoms. Follow-up octreoscans after, respectively, 6 and 12 months showed the unequivocal presence of a bronchial carcinoid in both patients. OBJECTIVE: The objective of the study was to correlate in vivo and in vitro findings in patients with ectopic ACTH producing syndrome. METHODS: We determined the expression of somatostatin and dopamine receptors by immunohistochemistry (patients 1 and 2), quantitative PCR, and in vitro culturing of tumor cells (patient 1 only). IN VITRO RESULTS: Both tumors were strongly positive for somatostatin receptor type 2 (sst(2)) on immunohistochemistry, whereas one of the tumors (patient 1) was also dopamine receptor subtype 2 (D(2)) positive on both immunohistochemistry and quantitative PCR. Octreotide (a sst(2) preferring analog) and cabergoline (D(2) agonist) both decreased the ACTH levels in the cultured tumor cells of patient 1. CONCLUSION: We describe two patients with ACTH-producing bronchial carcinoids, in whom a direct down-regulatory effect of glucocorticoid levels on tumoral sst(2) receptor expression is suggested by a remarkable change in octreoscan status after successful mifepristone therapy. Further studies will have to demonstrate whether glucocorticoid lowering or antagonizing therapy may be used to improve the diagnostic accuracy of somatostatin receptor scintigraphy in patients with ectopic ACTH production of unknown primary origin. PMID- 22090284 TI - Adaptive behaviour, tri-trophic food-web stability and damping of chaos. AB - We examine the effect of adaptive foraging behaviour within a tri-trophic food web with intra-guild predation. The intra-guild prey is allowed to adjust its foraging effort so as to achieve an optimal per capita growth rate in the face of realized feeding, predation risk and foraging cost. Adaptive fitness-seeking behaviour of the intra-guild prey has a stabilizing effect on the tri-trophic food-web dynamics provided that (i) a finite optimal foraging effort exists and (ii) the trophic transfer efficiency from resource to predator via the intra guild prey is greater than that from the resource directly. The latter condition is a general criterion for the feasibility of intra-guild predation as a trophic mode. Under these conditions, we demonstrate rigorously that adaptive behaviour will always promote stability of community dynamics in the sense that the region of parameter space in which stability is achieved is larger than for the non adaptive counterpart of the system. PMID- 22090283 TI - A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery. AB - Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative--hollow nerve guidance conduits (NGCs)--have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell-material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic. PMID- 22090286 TI - Determination and validation of the elastic moduli of small and complex biological samples: bone and keratin in bird beaks. AB - In recent years, there has been a surge in the development of finite-element (FE) models aimed at testing biological hypotheses. For example, recent modelling efforts suggested that the beak in Darwin's finches probably evolved in response to fracture avoidance. However, knowledge of the material properties of the structures involved is crucial for any model. For many biological structures, these data are not available and may be difficult to obtain experimentally given the complex nature of biological structures. Beaks are interesting as they appear to be highly optimized in some cases. In order to understand the biomechanics of this small and complex structure, we have been developing FE models that take into account the bilayered structure of the beak consisting of bone and keratin. Here, we present the results of efforts related to the determination and validation of the elastic modulus of bone and keratin in bird beaks. The elastic moduli of fresh and dried samples were obtained using a novel double-indentation technique and through an inverse analysis. A bending experiment is used for the inverse analysis and the validation of the measurements. The out-of-plane displacements during loading are measured using digital speckle pattern interferometry. PMID- 22090285 TI - Effects of surface microtopography on the assembly of the osteoclast resorption apparatus. AB - Bone degradation by osteoclasts depends on the formation of a sealing zone, composed of an interlinked network of podosomes, which delimits the degradation lacuna into which osteoclasts secrete acid and proteolytic enzymes. For resorption to occur, the sealing zone must be coherent and stable for extended periods of time. Using titanium roughness gradients ranging from 1 to 4.5 um R(a) as substrates for osteoclast adhesion, we show that microtopographic obstacles of a length scale well beyond the range of the 'footprint' of an individual podosome can slow down sealing-zone expansion. A clear inverse correlation was found between ring stability, structural integrity and sealing-zone translocation rate. Direct live-cell microscopy indicated that the expansion of the sealing zone is locally arrested by steep, three-dimensional 'ridge-like barriers', running parallel to its perimeter. It was, however, also evident that the sealing zone can bypass such obstacles, if pulled by neighbouring regions, extending through flanking, obstacle-free areas. We propose that sealing-zone dynamics, while being locally regulated by surface roughness, are globally integrated via the associated actin cytoskeleton. The effect of substrate roughness on osteoclast behaviour is significant in relation to osteoclast function under physiological and pathological conditions, and may constitute an important consideration in the design of advanced bone replacements. PMID- 22090287 TI - Apoptosis induced by ZnPcH1-based photodynamic therapy in Jurkat cells and HEL cells. AB - Photodynamic therapy (PDT) can selectively and effectively kill tumor cells, and photosensitization is the key to these anti-tumor effects. In this study, we investigated the killing mechanisms of the photosensitizer ZnPcH1 (a mono-alpha substituted zinc(II) phthalocyanine synthesized in China), in the acute lymphoid leukemia cell line Jurkat and the acute erythroleukemia cell line HEL. Results from acridine orange/ethidium bromide fluorescence staining, DNA gel electrophoresis, and Annexin-V(FITC/PI) double-stained flow cytometry analysis indicated that ZnPcH1-PDT induced apoptosis in Jurkat and HEL cells, with Jurkat cells being more sensitive. Following ZnPcH1-PDT treatment, upregulation of p53 and Bax, downregulation of HSP70, Bcl-2 and Akt, and inhibition of the phosphorylation of Akt and GSK3beta were observed. Our results establish a theoretical basis for the application of ZnPcH1-PDT in the treatment of acute leukemia. PMID- 22090288 TI - [Genotyping of nosocomial methicillin-resistant Staphylococcus aureus strains isolated from clinical specimens by rep-PCR]. AB - Methicillin-resistant Staphylococcus aureus (MRSA) infections are associated with increased cost, mortality and length of hospital stay compared with the other infections. Therefore, controlling the spread of this pathogen by screening patients, personnel and the environment remains as a high priority in infection control programs. The aim of this study was to detect the clonal relationship between nosocomial MRSA strains by using repetitive-sequence-based polymerase chain reaction (rep-PCR) method which has several advantages owing to its speed and ease of use. A total of 100 MRSA stock strains that had been isolated from various clinical samples of hospitalized patients in Erciyes University Medical Faculty Hospitals between September 2008-October 2009, were included in the study. Methicillin resistance of the strains were determined by cefoxitin disc diffusion test according to CLSI guidelines. Rep-PCR (Diversilab, bioMerieux, France) method was performed in the following four steps in order to determine genetic proximity of MRSA strains: (1) Manual DNA extraction (UltraClean Microbial DNA Isolation Kit; MoBio Laboratories, USA), (2) Rep-PCR by using fingerprinting kits in the thermocycler (Diversilab DNA Fingerprinting Kit), (3) Automated microfluidic electrophoresis by bioanalyzer (Diversilab DNA LabChip kit), (4) Analysis and rapid evaluation with the use of web-based DiversiLab software (version 2.1.66). Rep-PCR analysis have shown the presence of a total 11 clones, including 3 major clones [A (4 subtypes), B (2 subtypes) and C (2 subtypes)] and 8 unique clones (DK). Clone A was found to be the dominant type. Seventy-eight percent of the 100 MRSA isolates belonged to clone A (63 were A1; 9 were A2; 4 were A3, 2 were A4), 11% belonged to clone B (10 were B1, 1 was B2), 3% belonged to clone C (2 were C1, 1 was C2), and one of each belonged to the other clones (D, E, F, G, H, I, J, K). Clone A was isolated from 93.3% (14/15) of the samples sent from internal diseases intensive care unit (ICU), from 66.6% (10/15) of the samples sent from infectious diseases ward and 91% (10/11) of hematology-oncology ward samples. All MRSA strains isolated from anesthesiology and newborn ICU were of clone A. The isolation dates of these strains were in proximity. In conclusion, MRSA strains showed clonal dissemination in our hospital, clone A being the predominant one during the study period. Rep-PCR which is a rapid and reliable method, can easily be applied for molecular epidemiological purposes and aid to infection control measures. PMID- 22090289 TI - [Evaluation of rapid genotype assay for the identification of gram-positive cocci from blood cultures and detection of mecA and van genes]. AB - Rapid and accurate identification of bacterial pathogens grown in blood cultures of patients with sepsis is crucial for prompt initiation of appropriate therapy in order to decrease related morbidity and mortality rates. Although current automated blood culture systems led to a significant improvement in bacterial detection time, more rapid identification systems are still needed to optimise the establishment of treatment. Novel genotype technology which is developed for the rapid diagnosis of sepsis, is a molecular genetic assay based on DNA multiplex amplification with biotinylated primers followed by hybridization to membrane bound probes. The aim of this study was to evaluate the performance of "Genotype(r) BC gram-positive? test for the identification of gram-positive cocci grown in blood cultures and rapid detection of mecA and van genes. This test uses DNA.STRIP(r) technology which includes a panel of probes for identification of 17 gram-positive bacterial species and is able to determinate the methicillin and vancomycin resistance mediating genes (mecA and vanA, vanB, vanC1, vanC2/C3) simultaneously, in a single test run. A total of 55 positive blood cultures from BACTECTM Plus/F (Becton Dickinson, USA) aerobic and pediatric blood culture vials were included in the study. The isolates which exhibit gram-positive coccus morphology by Gram staining were identified by Genotype (r) BC gram-positive test (Hain Life Science, Germany). All of the samples were also identified with the use of Phoenix PMIC/ID Panel (Becton Dickinson, USA) and antibiotic susceptibilities were determined. Of the 55 blood culture isolates, 17 were identified as Staphylococcus epidermidis [all were methicillin-resistant (MR)], 9 were S.aureus (one was MR), 18 were S.hominis (10 were MR), 4 were E.faecalis, 3 were E. faecium (one was vanconycin-resistant), 2 were S.saprophyticus (one was MR), 1 was S.warneri and 1 was S.haemolyticus, by Phoenix automated system. Genotype(r) BC gram-positive test results revealed consistency with Phoenix system regarding bacterial identification in 46 (83.6%) of the samples. The two bacteria identified as S.saprophyticus by the Phoenix system could not be identified by the Genotype(r) BC test since this species were not included in the identification panel of the system, however, mecA gene were detected in these two samples by Genotype(r) BC test. Genotype(r) BC test detected mecA gene in five samples which were not detected as methicillin resistant by the Phoenix system. Besides polymicrobial growth was determined in five samples by Genotype (r) BC test, but not by the automated system. One E.faecium isolate with vanA gene was correctly identified by Genotype(r) BC test. In conclusion, Genotype(r) BC gram positive test is a fast and reliable test for the identification of the most important gram-positive pathogens and mecA and van genes directly from positive blood culture bottles. This test was also found superior than the automated Phoenix system regarding the detection of polymicrobial growth. These data indicated that, routine use of DNA strip technology-based assay would be useful for clinical diagnosis in patients with sepsis. PMID- 22090290 TI - [Investigation of plasmid-mediated quinolone resistance in Pseudomonas aeruginosa strains isolated from cystic fibrosis patients]. AB - Pseudomonas aeruginosa which is widely found in the environment, may lead to serious nosocomial infections. Due to its intrinsic resistance to many antibacterial agents, treatment of P.aeruginosa infections usually present difficulty. Quinolones, especially ciprofloxacin, are crutial antibiotics for the treatment of P.aeruginosa infections. However resistance developing to quinolones may become an important problem. Resistance to quinolones is often a result of chromosomal mutations and by the effect of efflux pumps. Recently plasmid mediated quinolone resistance have been reportedin the members of Enterobacteriaceae family. The gene responsible for this resistance is called qnr. In addition to qnr genes there is also another gene called aac(6?)-Ib-cr responsible for plasmid-mediated quinolone resistance and aminoglycoside resistance. Limited studies which to screen P.aeruginosa strains for the presence of qnr gene region, revealed no positivity. The aim of this study was to investigate the plasmid-mediated quinolone resistance in P.aeruginosa strains isolated from cystic fibrosis patients. A total of 110 P.aeruginosa strains isolated from respiratory tract specimens from the patients were included in the study. Ciprofloxacin susceptibilities of the isolates were detected by Kirby Bauer disk diffusion method according to CLSI guidelines. The presence of qnrA, qnrB, qnrC, qnrS and aac(6')-Ib-cr genes were searched by multiplex polymerase chain reaction (PCR) with the use of specific individual primer pairs. As positive control strains, Escherichia coli J53 pMG252 (qnrA1 positive), E.coli J53 pMG252 (qnrS1 positive), E.coli J53 pMG258 (qnrB1 and aac(6')-Ib-cr positive), Klebsiella pneumoniae ref.15 (qnrB positive), Enterobacter cloacae ref.287 (qnrS positive), E.coli ref.20 (qnrA positive) and E.coli DH10 conjugated with pHS11 plasmid (qnrC positive) were used. Of 110 P.aeruginosa clinical isolates, 13 were found resistant to ciprofloxacin, while 7 were intermediate. However multiplex PCR yielded no positivity in terms of qnrA, qnrB, qnrC, qnrS and aac(6')-Ib-cr gene regions. In conclusion, although our results indicated that none of the tested P.aeruginosa strains harboured those genes, further multicenter studies with large numbers of isolates are needed to confirm these results. PMID- 22090291 TI - [Antimicrobial resistance profiles of Shigella spp. isolated from feces samples in Hacettepe University Ihsan Dogramaci Children's Hospital between 1999-2010]. AB - The symptoms of infections caused by Shigella spp. are diverse and may change from person to person. The choice of antibiotics as well as the prevention of the loss of fluid and electrolytes are important in the clinical recovery. The local resistance rates to antibiotics should be taken into consideration when planning empirical therapy. The aims of this retrospective study were to detect the in vitro antimicrobial susceptibility of 605 Shigella spp. strains isolated from feces samples of children at Hacettepe University Ihsan Dogramaci Children's Hospital between 1999 and 2010 and to compare the resistance rates by years. Susceptibility to ampicillin, cefotaxime, trimethoprim/sulfamethoxazole (T/S), nalidixic acid, and ciprofloxacin were determined in Mueller-Hinton Agar by disk diffusion method according to CLSI criteria. Among a total of 605 Shigella strains, 526 were identified as S.sonnei, 69 as S.flexneri, nine as S.boydii and one as S.dysenteriae. Resistance rates to ampicillin, cefotaxime, T/S and nalidixic acid were 24.3%, 3.6% 74.2% and 4.6%, respectively. All of the isolates were found susceptible to ciprofloxacin. Antibiotic resistance rates of the isolates did not exhibit any differences between the years. S.dysenteriae was isolated once in 2003 throughout this 12 year survey and the isolate was found susceptible to T/S and ciprofloxacin. A significant yearly decrease was detected in the number of stool cultures and number of Shigella spp. isolated in stool (p< 0.001). Ampicillin resistance was higher in S.flexneri (77.8%) and S.boydii (62.5%) than S.sonnei (17%). However, T/S resistance was higher in S.sonnei (78.9%) than S.flexneri (52.5%) and S.boydii (11.1%). In conclusion, continuous surveillance of resistance among Shigella species in Turkey seems to be imperative for establishing empirical treatment guidelines in our country. PMID- 22090292 TI - [Evaluation of blood agar medium for the growth of mycobacteria]. AB - This study was aimed to evaluate the performance of blood agar for the growth of mycobacteria from clinical specimens sent to Mycobacteriology Laboratory of Samsun Chest Diseases Hospital. One hundred fifty six clinical specimens including 123 sputum, 28 bronchoalveolar lavage (BAL) and 5 pleural fluid specimens were inoculated in Lowenstein-Jensen (LJ), BACTEC MGIT 960 system (Becton Dickinson, USA) and blood agar following decontamination process. The specimens were also simultaneously examined for the presence of acid-fast bacilli (AFB). Thirty five mycobacteria strains (33 Mycobacterium tuberculosis and 2 atypical mycobacteria) grew in blood agar, 38 (36 M.tuberculosis and 2 atypical mycobacteria) in LJ media and 46 (44 M.tuberculosis and 2 atypical mycobacteria) in BACTEC MGIT 960 system. Among 29 AFB negative specimens, 20 revealed growth in both blood agar and LJ medium and 27 in MGIT system. AFB positive 20 samples yielded growth in 15 samples in blood agar, 18 in LJ medium and 19 in MGIT system. Among the total of 156 samples, contamination was observed in 15 (9.6%) samples in blood agar, 16 (10.2%) in LJ medium and 18 (11.5%) in MGIT system. Growth time was 5-35 days (mean 18 +/- 7.4), 11-35 days (mean 19 +/- 5.9) and 5 15 days (mean 10 +/- 2.4) for blood agar, LJ medium and BACTEC MGIT 960 system, respectively. The three samples which revealed contamination in BACTEC MGIT 960 system, grew successfully in both blood agar and LJ medium without contamination. In one sample, growth was observed only in LJ medium but neither in blood agar nor BACTEC MGIT 960 system. However, in another sample, growth was observed only in blood agar while no growth was detected in LJ or BACTEC MGIT 960 system. Six samples yielded mycobacteria only in BACTEC MGIT 960 system. These results indicated that simultaneous use of one liquid and one solid medium to grow mycobacteria from the clinical samples seemed to be complementary. Blood agar was a promising choice since it was found to be as effective as LJ medium for the growth of mycobacteria, however, this issue needs to be further evaluated in a multicentre study with a larger specimen collection. PMID- 22090293 TI - [Comparison of proportion method in Lowenstein-Jensen medium with the BACTEC 460 TB system for antimycobacterial susceptibility testing of Mycobacterium tuberculosis isolates]. AB - This study was conducted to compare BACTEC 460 TB system and the proportion method in commercially available and ready to use antibiotic added Loweinstein Jensen (LJ) medium for susceptibility testing of first line drugs in Mycobacterium tuberculosis complex isolates. A total 238 M.tuberculosis strains isolated from clinical samples in our laboratory between 2006-2010 period were included in the study. Susceptibility testing for streptomycin, isoniazid, rifampicin and ethambutol in commercially provided LJ medium (Salubris Inc., Istanbul) was performed by the proportion method as recommended by the manufacturer, and the results were compared with the results of BACTEC 460 TB (Becton Dickinson, USA) system. Resistance rates of M.tuberculosis strains against streptomycin, isoniasid, rifampicin and ethambutol obtained by BACTEC 460 TB system were 19.7%, 42%, 40.8% and 18%, respectively. Those rates were 22.7%, 38.7%, 37% and 15.5%, respectively, by antibiotic added LJ proportion method. There was no statistically significant difference between the two methods in terms of resistance rates (p> 0.05). The rates of consistency between proportion method in LJ medium and BACTEC 460 TB system for streptomycin, isoniasid, rifampicin and ethambutol susceptibility were found as 85.3%, 92.4%, 95.4% and 92.4%, respectively. When comparing the reporting time (interval between beginning of the process to reporting of the results) of the methods, minimal, maximal and average reporting spans for BACTEC 460 TB system were 5, 12 and 8.08 +/- 2.65 days, and 15, 42 and 23.89 +/- 6.02 days for the proportion method in LJ medium, respectively, being statistically significant (p= 0.001). It was determined that the sensitivity test results of major antimycobacterial drugs in commercial LJ medium were compatible with the BACTEC 460 TB system. Nonetheless, the rate of incompatible results was higher for STR than the other drugs. Although there has been some disadvantages such as longer reporting time, need for experience in manual processing and visual evaluation, standardized LJ media approved for quality can be used for susceptibility testing of M.tuberculosis in the laboratories which do not have eligible conditions for the establishment of automated systems. PMID- 22090294 TI - [Development and optimization of an in-house PCR method for molecular diagnosis of pertussis]. AB - Pertussis (whooping cough), caused by Bordetella pertussis is a severe, acute contagious disease of the respiratory system and it affects mostly children and also susceptible individuals of all ages. Although the conventional culture method used for diagnosis is highly specific, it has a lower sensitivity. Therefore, there is a need for a sensitive, specific and rapid method for diagnosis of pertussis. Polymerase chain reaction (PCR), introduced recently as a new approach for diagnosis of pertussis, has been shown to be more sensitive than culture method. Pertussis toxin gene (ptxA-Pr), insertion sequence genes (IS481 and IS1001), adenylate cyclase genes and structural porin and flagellin genes were chosen as targets for PCR, in different studies. This study aimed to develop and optimize a diagnostic inhouse PCR method by using primers specific for ptxA Pr and IS481 gene regions. An in-house PCR method was developed by using primer pairs of PTp1/PTp2 specific for ptxA-Pr gene and PIp1/PIp2 specific for IS481 gene and DNAs of various bacterial reference strains. Throat samples obtained from 45 healthy individuals and B.pertussis reference strain with decreasing concentrations were mixed to constitute a group of "representative clinical samples" and used to test and optimize sensitivity and specificity of the method. The in-house PCR with PTp1/PTp2 primers showed a very high specificity but a low sensitivity with a value of 34.4 cfu/Rm (colony forming unit/reaction mixture). Whereas, the inhouse PCR with PIp1/PIp2 primers exhibited a low specificity due to cross-reactivity with B. Pertussis and B.bronchiseptica but much higher sensitivity with a value of 1.12 cfu/Rm. The experiments performed with the representative clinical samples yielded similar results. Simultaneously applied cultivation studies indicated the detection limit of the PCR method as 2 x 103 cfu/ml. Based on our results, the PCR targeting IS481 gene had high sensitivity while the PCR targeting ptxA-Pr gene had high specificity. It was concluded that, PCR method targeting the IS481 gene might be used for pre-diagnosis and then PCR for ptxA-Pr gene might be applied for the confirmation of B.pertussis in the molecular diagnosis of pertussis. PMID- 22090295 TI - [Evaluation of vancomycin-resistant enterococcus colonization at Gaziantep Children's Hospital, Turkey]. AB - Enterococci are members of normal flora of human gastrointestinal system, and occupy the first places among the agents causing nosocomial infection. The most frequent origin of vancomycin-resistant enterococcus (VRE) is the gastrointestinal colonization in hospitalized patients. Prolonged hospitalization, long-term antibiotic use and severe underlying diseases increase the risk of VRE colonization. Routine VRE surveillance of high-risk group patients is crucial for early detection and implementation of precautions to impede the development of infection and spread of VRE. The aim of this study was to evaluate the status of VRE colonization in Oncology Department of Gaziantep Children's Hospital, Turkey, following a VRE isolation from the urine sample of a patient (index case). In the first phase of this point prevalence study VRE screening was done after positive VRE result was obtained from the index case, and in the second phase VRE colonization rate was investigated after the implementation of infection control policies. Perirectal swab samples collected from patients were cultivated into supplemented VRE agar base (Oxoid, UK) including vancomycin 6 ug/ml and 5% sheep blood agar. The isolates were identified by conventional methods together with API 20 Strep (bioMerieux, France) and VITEK2 (bioMerieux, France) identification systems. Vancomycin (30 ug) and teicoplanin (30 ug) susceptibilities of the isolates were investigated by Kirby-Bauer disc diffusion method according to CLSI criteria. In addition, VITEK2 antibiogram cards, AST-592 were used to determine antibiotic susceptibilities. In the first phase of the surveillance a total of 123 perirectal swab specimens obtained from patients staying at oncology, burn, pediatric surgery and intensive care units (ICU) were investigated and the rate of VRE colonization was determined as 14.6% (18/123). Thirteen of the VRE colonized patients were from oncology wards and five were from ICU. Upon the detection of VRE colonization, contact isolation was implemented and hospital staff was educated for hand washing and restricted antibotic use policies were established. To evaluate the efficacy of infection control implementations, perirectal swab samples were collected from 242 patients under antibiotic treatment and hospitalized in several wards and ICU for >= 3 days. The results of this second control surveillance revealed that VRE colonization rate declined to 3.3% (8/242), and three of these VRE colonized patients were in the ICU, three in the oncology ward and one of each in burn and pediatric wards. During the study period blood stream infection developed in three of the previously colonized oncology patients of whom one patient also had simultaneous pneumoniae due to VRE. The results of this study indicated the importance of VRE surveillance at the hospital setting. The determination of the VRE colonization in the hospital will help the implementation of appropriate infection control measures and eventually decrease the rate of nosocomial VRE infection. PMID- 22090296 TI - [Investigation of Brucella canis seropositivity by in-house slide agglutination test antigen in healthy blood donors]. AB - Canine brucellosis which is due to Brucella canis, is transmitted to man by infected dogs or their secretions. The symptoms of canine brucellosis are similar to the symptoms of brucellosis caused by other Brucella species and endocarditis or meningitis may develop in untreated cases. There is limited data regarding B.canis infections in man and the current status of the disease is insufficiently evaluated in our country. Serological diagnosis of brucellosis is classically based on standard slide and tube agglutination tests. However, the antigens used in these tests detect antibodies that develop against species (B.melitensis, B.abortus, B.suis) with "smooth" lipopolysaccharides in their cell wall. B.canis has "rough" lipopolysaccharide in its cell wall and thus these classical tests can not detect antibodies against B.canis. Besides there is no commercial slide agglutination test which uses B.canis antigens. The aim of this study was to investigate the B.canis seropositivity by slide agglutination test (SAT), using homemade B.canis antigen, in healthy subjects and to determine the prevalence of B.canis infection in our population. A total of 1930 blood donors (age range: 18 55 years) who were admitted to the blood donation centers of different hospitals in Kocaeli province (located at Northwestern part of Turkey) between January December 2010, have been included in the study. All of the subjects were negative in terms of Rose-Bengal plate test (B.abortus antigen test). Undiluted serum samples were initially screened by SAT, and those which were found positive were retested by SAT in the dilutions of 1/25 - 1/200. Confirmation of the positive results was performed by using 2-mercaptoethanol (2-ME) SAT. The test antigen (Alton antigen) was prepared from the less mucoid M(-) variant of B.canis, and 1/1048 titered dog antiserum was used as positive control. Of the 1930 blood donors sera, 40 (2.1%) were found positive with SAT, whereas 16 of them yielded equivocal positive (12 were 1/50, 4 were 1/100 titers) and 15 yielded positive (>= 1/200 titer) results with 2-ME SAT. As a result, B.canis seropositivity rate in the healthy subjects in this study was estimated as 1.6% (31/1930). The integration of B.canis SAT to the routine serological tests applied for brucellosis diagnosis might aid to the data related to brucellosis epidemiology. B.canis seroprevalence determined as 1.6% in this study supplied a basic data about the infection in our country. However, larger scale, multicenter studies with different patient and risk groups should be conducted to further evaluate the epidemiology of B.canis infections in Turkey. PMID- 22090297 TI - [A real-time PCR assay for the quantification of hepatitis B virus DNA and concurrent detection of YMDD motif mutations]. AB - Monitoring therapy in chronic hepatitis B patients receiving lamivudine therapy, is done by two different assays; determination of viral load and genotypic resistance. These methods are labor intensive and time consuming. It was aimed to develop an assay to quantitate hepatitis B virus (HBV) DNA in serum and detect YMDD (thyrosine, methionine, aspartate, aspartate) motif mutations in the same run. The assay was based on real-time polymerase chain reaction (Rt-PCR) with YMDD-specific hybridization probes. Determination of YMDD motif was done by melting temperature analysis. External standard curve was used for quantifying viral DNA, which was generated by standard sera (VQC S2220) including HBV-DNA between concentrations of 1000 to 3 million copies/ml. The assay was compared with commercial quantitative kit (Artus HBV RG PCR; Qiagen, Germany), commercial line prob assay (INNO-LiPA HBV DR v1.0; Innogenetics, Belgium) and direct DNA sequencing method. Thirty-eight serum samples obtained from 20 chronic hepatitis B patients (7 female, 13 male; age range: 27-70 years) treated with only lamivudine and were negative for HIV and HCV antigen and antibodies were tested in the study. The analytical sensitivity of the assay was found as 200 copies/ml, with a dynamic range of 1 x 103 to 3 x 107 copies/ml. PCR efficiency of the in house assay was found to be 1.98. Comparison of log10 HBV-DNA concentrations determined by the in-house and commercial quantitative kits showed a significant correlation (r= 0.681). Melting temperature (Tm) analysis was used for the YMDD motif determination and found to be 59.86 degrees C for YMDD, 56.34 degrees C for YVDD and 55.10 degrees C for YIDD. The results of the in-house assay, DNA sequencing and LiPA were concordant in samples with homogeneous virus population, and in-house assay could also detect the major type of YMDD motif in mixed viral populations The Rt-PCR method which was developed in this study is a rapid, accurate and reproducible method for quantifying HBV-DNA and detecting the predominant YMDD motif in the same run in two hours duration. It was concluded that this method may be a convenient tool for monitoring HBV-infected patients receiving lamivudine treatment. PMID- 22090298 TI - [Investigation of Epstein-Barr virus and herpes simplex virus markers by serological and molecular methods in patients with rheumatoid arthritis and systemic lupus erythematosus]. AB - Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) which are autoimmune diseases usually questioned for their association with many infectious agents have etiopathogenesis related to genetic, immunologic, hormonal and even environmental factors. The most commonly attributed etiologic agents are herpes group viruses. The aim of this study was to investigate the role of Epstein-Barr virus (EBV) and herpes simplex (HSV) viruses in the etiology of RA and SLE. A total of 137 patients (87 RA and 50 SLE; mean age: 33 +/- 12 years) who were admitted to Eskisehir Osmangazi University Medical Faculty Rheumatology Department between January 2007-January 2008 and diagnosed according to 1987 ACR (American College of Rheumatology) criteria have been included in the study, together with 50 healthy blood donors (mean age: 35 +/- 14 years) as control group. Serum samples obtained from all of the cases were tested for EBV VCA-IgG, VCA-IgM, EA/D-IgG and EBNA-IgG (Trinity Biotech, USA); IgM and IgG antibodies against HSV-1 and HSV-2 by ELISA method (Dia-Pro Diagnostic, Italy), and the presence of viral nucleic acids in blood samples were investigated by real-time quantitative polymerase chain reaction (RTPCR; Qiagen, USA). EBV VCA-IgM was negative in all of the RA, SLE and control group patients. VCA-IgG positivity were 98% and 96%, and for EBNA-IgG 98.5% and 100%, in patient and control groups, respectively. There was no statistically significant difference between the groups regarding VCA-IgG and EBNA- IgG positivity (p> 0.05). On the other hand, EBV EA/D-IgG positivity rate found in the SLE group (34%) was significantly higher than RA (7%) and control (12%) groups (p< 0.001 and p< 0.05, respectively). There was no significant difference between RA and control groups in terms of EA/D-IgG positivity (p> 0.05). Regarding herpes simplex virus serology, HSV1-IgG seropositivity were 99% and 94% and HSV2-IgG positivity were 8% and 12% in the patient and control groups, respectively. There was no statistically significant difference between the groups according to the positivity rates of IgM and IgG specific for HSV-1 and HSV-2 (p> 0.05). All of the cases were found negative in terms of EBV, HSV-1 and HSV- 2 DNAs according to double-checked RT-PCR results. In conclusion, no significant difference was determined for EBV and HSV serologic markers in RA and SLE patients compared to the control group. However, significantly higher rate of EBV EA/D-IgG positivity in SLE patients might have indicated a possible association between SLE and EBV infection. Larger scale, prospective studies including examination of the synovial fluid/tissue samples are required to enlighten the association between SLE and EBV. PMID- 22090299 TI - [Pandemic influenza A (H1N1)v vaccination status and factors affecting vaccination: Ankara and Diyarbakir 2009 data from Turkey]. AB - In this study, it was aimed to determine the frequency of the symptoms of influenza-like illness during influenza A (H1N1)v pandemic in two provinces where sentinel influenza surveillance was conducted and also to obtain opinions about H1N1 influenza and vaccination, H1N1 vaccination status and factors affecting vaccination. This cross-sectional study was conducted in the provinces of Ankara (capital city, located at Central Anatolia) and Diyarbakir (located at southeastern Anatolia). It was planned to include 455 houses in Ankara and 276 houses in Diyarbakir. The household participation rate in the study was 78.9% and 53.6% for Ankara and Diyarbakir, respectively. Our study was carried out between January-February 2010, with 1164 participants from Ankara and 804 from Diyarbakir, including every household subjects except for infants younger than 11 months and patients with primary/secondary immunodeficiency diseases. Data was collected by site teams consisting of a physician and a healthcare staff with informed consent. Of the participants 45.5% from Ankara and 35.3% from Diyarbakir stated that they had gone through an influenza-like illness. The most frequently indicated clinical symptoms were fatigue/weakness, rhinitis, sore throat and cough. The rates of admission to a physician with influenza like illness complaints were 50.6% and 58.7%; rates of hospitalization due to influenza-like illness were 1% and 1.5%, and rates of antiviral drug use were 3.8% and 1.9%, in Ankara ve Diyarbakir participants, respectively. The rate of personal precautions taken by the subjects for prevention from pandemic influenza were 59% and 53.3%, in Ankara and Diyarbakir, respectively. These precautions most frequently were "hand washing" and "avoiding crowded public areas". H1N1 influenza vaccine was applied in 9.3% of the participants in Ankara and in 3.7% of the participants in Diyarbakir. Vaccination rate was higher in both of the provinces in adults over 25 years old than children and adolescents and in patients with chronic underlying disease. None of the 25 pregnant participants were vaccinated against pandemic influenza. The educational background, employment status and quality of the job have been detected as factors affecting the status of being vaccinated with H1N1 influenza vaccine in both provinces. In addition, the percentage of having H1N1 influenza vaccination was found to be higher in subjects who had seasonal influenza vaccination previously and in 2009, than those who had not, and this difference was statistically significant in both provinces (Ankara p< 0.001, Diyarbakir p< 0.001). The mostly indicated post-vaccination adverse reactions reported by vaccinated participants were local sensitivity, muscle and joint pains, headache and malaise. The most frequent rationale for not being vaccinated against H1N1 were "I do not consider it necessary/I do not want" (Ankara 33.4%, Diyarbakir 27.4%) and "I do not believe/trust its efficacy" (Ankara 25.6%, Diyarbakir 22.6%). Those data emphasized the insufficient awareness of our population about the importance of pandemic influenza and vaccine. It is also believed that possible case definition in H1N1 case management scheme should be revised. In conclusion an important part of pandemic preparation plans is risk communication with the public to increase awareness and to prevent the missed opportunities. PMID- 22090300 TI - [In vitro biofilm formation and relationship with antifungal resistance of Candida spp. isolated from vaginal and intrauterine device string samples of women with vaginal complaints]. AB - Intrauterin device (IUD) application is a widely used effective, safe and economic method for family planning. However IUD use may cause certain changes in vaginal ecosystem and may disturb microflora leading to increased colonization of various opportunistic pathogen microorganisms. The aims of this study were (i) to detect the biofilm production characteristics of Candida spp. isolated from vaginal and IUD string samples of women with IUDs, and (ii) to investigate the relationship between biofilm production and antifungal resistance. A total of 250 women (mean age: 34.4 +/- 7.6 years) admitted to gynecology outpatient clinics with vaginal symptoms (discharge and itching) were included in the study. The patients have been implanted CuT380a type IUDs for a mean duration of 59.8 +/- 42.4 months. Without removing IUD, string samples were obtained by cutting and simultaneous vaginal swab samples were also collected. Isolated Candida spp. were identified by conventional methods and API 20C AUX (BioMerieux, Fransa) system. Minimal inhibitory concentrations (MIC) of fluconazole, itraconazole and amphotericin B were determined by broth microdilution method according to the CLSI guidelines. Biofilm formation was evaluated by crystal violet staining and XTT-reduction assays, and the isolates which yielded positive results in both of the methods were accepted as biofilm-producers. In the study, Candida spp. were isolated from 33.2% (83/250) of the vaginal and 34% (85/250) of the IUD string samples, C.albicans being the most frequently detected species (54 and 66 strains for the samples, respectively). The total in vitro biofilm formation rate was 25% (21/83) for vaginal isolates and 44.7% (38/85) for IUD string isolates. Biofilm formation rate of vaginal C.albicans isolates was significantly lower than vaginal non-albicans Candida spp. (14.8% and 44.8%, respectively; p= 0.003). Biofilm formation rate of C.albicans strains isolated from vaginal and IUD string samples were found as 14.8% (8/54) and 45.5% (30/66), with a statistically significant importance (p< 0.001). However, no statistically significant difference was detected for biofilm formation rates of non-albicans Candida spp. when sample types were considered [44.8% (13/29) and 42.1% (8/19), respectively; p> 0.05]. Fluconazole resistance was significantly higher in biofilm-producing vaginal Candida spp. than those of nonproducers (52.4% vs. 16.1%; p= 0.001), however, itraconazole resistance was found similar in biofilmproducer and non producer isolates (47.6% vs. 32.3%; p> 0.05). Resistance rates for both fluconazole and itraconazole were higher in biofilm-producers (39.5% and 52.6%, respectively), than those of non-producers (10.6% and 29.8%, respectively), representing a statistical significance (p= 0.002 and p= 0.03, respectively) for Candida spp. strains isolated from IUD string samples. The overall resistance rates of C.albicans and non-albicans Candida spp. against fluconazole, were determined as 15% and 54.2%, respectively, while those rates were 24.2% and 68.7%, respectively, against itraconazole. MIC value of amphotericin B for all of the Candida spp. isolates was <= 1.5 ug/ml. In conclusion, the data obtained from this study revealed that Candida spp. May lead to vaginal infections by inducing biofilm formation in IUD strings and these biofilms may be related to resistance to antifungal agents. Thus, women using IUDs should be followed-up periodically for the development of biofilms in their IUD strings. PMID- 22090301 TI - [Evaluation of Malassezia species by Fourier transform infrared (FT-IR) spectroscopy]. AB - Malassezia species which are lipophilic exobasidiomycetes fungi, have been accepted as members of normal cutaneous flora as well as causative agent of certain skin diseases. In routine microbiology laboratory, species identification based on phenotypic characters may not yield identical results with taxonomic studies. Lipophilic and lipid-dependent Malassezia yeasts require lipid-enriched complex media. For this reason, Fourier transform infrared (FT-IR) spectroscopy analysis focused on lipid window may be useful for identification of Malassezia species. In this study, 10 different standard Malassezia species (M.dermatis CBS 9145, M.furfur CBS 7019, M.japonica CBS 9432, M.globosa CBS 7966, M.nana CBS 9561, M.obtusa CBS 7876, M.pachydermatis CBS 1879, M.slooffiae CBS 7956, M.sympodialis CBS 7222 and M.yamatoensis CBS 9725) which are human pathogens, have been analyzed by FT-IR spectroscopy following standard cultivation onto modified Dixon agar medium. Results showed that two main groups (M1; M.globosa, M.obtusa, M.sympodialis, M.dermatis, M.pachydermatis vs, M2; M.furfur, M.japonica, M.nana, M.slooffiae, M.yamatoensis) were discriminated by whole spectra analysis. M.obtusa in M1 by 1686-1606 cm-1 wavenumber ranges and M.japonicum in M2 by 2993-2812 cm-1 wavenumber ranges were identified with low level discrimination power. Discriminatory areas for species differentiation of M1 members as M.sympodialis, M.globosa and M.pachydermatis and M2 members as M.furfur and M.yamatoensis could not be identified. Several spectral windows analysis results revealed that FT-IR spectroscopy was not sufficient for species identification of culture grown Malassezia species. PMID- 22090302 TI - [Acinetobacter baumannii: an important pathogen with multidrug resistance in newborns]. AB - Nosocomial sepsis agents with multidrug resistance have led to higher morbidity and mortality in premature infants in the recent years. Acinetobacter baumannii has become a leading cause of nosocomial sepsis in several neonatal intensive care units. In this study, the demographic, clinic, microbiologic characteristics and risk factors of 21 premature infants hospitalized in newborn intensive care unit between January 2010-February 2011 and developed A.baumannii infection, have been evaluated retrospectively. The isolates were identified by conventional methods and antibiotic susceptibility tests were performed by Vitek 2 GN and AST N090 using Vitek 2 Compact system (BioMerieux, France). A.baumannii was isolated from the blood samples of 10 patients, central venous catheter samples of three patients, CSF samples of two, tracheal aspirate of two and urine sample of one patient. In two patients both blood and central venous catheter samples and in one patient both blood and CSF samples revealed A.baumannii. Gestational age was between 22-30 weeks and birth weight was between 500-1320 grams (17 were < 1000 g) in 19 patients. A.baumannii caused early onset (<= 3 days) sepsis in four, and late onset (>= 4 days) sepsis in 17 patients. The main risk factors were detected as mechanical ventilation (n= 20, 95%), prematurity (n= 19, 91%), total parenteral nutrition (n= 17, 81%) and central catheter use (n= 14, 67%). Antibiotics with highest rates of susceptibility were gentamicin (18/21), amikacin (14/21), and colistin (10/21). Twenty (95%) isolates had multiple drug resistance. Amikacin, gentamicin, colistin and imipenem were used for treatment, however 12 infants, 8 of which due to sepsis, died. In conclusion, A.baumannii which is an important nosocomial sepsis agent with multidrug resistance, is increasing in incidence. To control Acinetobacter infections especially in low birth weight infants, the use of invasive procedures, total parenteral nutrition and broad spectrum antibiotics should be limited and infected patients should be isolated besides establishment of other appropriate infection control measures. PMID- 22090303 TI - [Genotypic identification and distribution patterns of Candida parapsilosis complex species (C.parapsilosis sensu stricto, C.metapsilosis and C.orthopsilosis) isolated from clinical samples]. AB - Candida parapsilosis, which has recently gained increasing importance, is the second most common fungal pathogen isolated from clinical specimens. C.parapsilosis strains exhibiting genetic heterogeneity were previously considered as a complex of three genetically different groups (group I, II, III). However, they have recently been reclassified as new species and named as C.parapsilosis sensu stricto (Grup I), C.orthopsilosis (Grup II) and C.metapsilosis (Grup III). In the present study we aimed to identify C.parapsilosis complex species by PCR-RFLP (Polymerase chain reaction-Restriction fragment lenght polymorphism) method and to determine the distribution of new species isolated from clinical specimens. A total of 68 samples (44 blood, 10 urine, 5 wound, 2 paracentesis fluids, 2 tympanocentesis samples and one of each cerebrospinal fluid, peritoneal fluid, surgical material, oral lesion and nail sample) in which C.parapsilosis had been isolated and identified with API 20C AUX (bioMerieux, France) between October 2005 - July 2009 in the Microbiology Laboratory of Karadeniz Technical University Hospital, in Trabzon, Turkey, were included in the study. Yeast genomic DNA was extracted using the "High Pure PCR Template Preparation Kit" (Roche Diagnostic, USA) and amplification of SADH gene was performed by using specific primers (S1-F sense; 5'-GTTGATGCTGTTGGATTGT-3' ve S1-R antisense; 5'-CAATGCCAAATCTCCCAA-3') with PCR. RFLP method was then applied by digesting PCR product (716 bp) with BanI enzyme (Fermentas, USA). In our study 98.5% (67/68) of the isolates were identified as C.parapsilosis sensu stricto, and 1.5% (1/68) was identifed as C.orthopsilosis, whereas no C.metapsilosis strains were detected. The strain identified as C.orthopsilosis was from a urine specimen and all the blood culture isolates were C.parapsilosis sensu stricto. In conclusion, the inability to differentiate C.parapsilosis complex species by phenotypical and routine tests leads to lack of knowledge in the clinical importance, isolation rates and geographical distribution of these species. Thus, genotypical identification of C.parapsilosis complex species will be the initial step for the arrangement of further studies in that area. PMID- 22090304 TI - [Pneumonia caused by Fusobacterium necrophorum: is Lemierre syndrome still current?]. AB - Fusobacterium necrophorum is a non-spore-forming gram-negative anaerobic bacillus that may be the causative agent of localized or severe systemic infections. Systemic infections due to F.necrophorum are known as Lemierre's syndrome, postanginal sepsis or necrobacillosis. The most common clinical course of severe infections in humans is a progressive illness from tonsillitis to septicemia in previously healthy young adults. A septic thrombophlebitis arising from the tonsillar veins and extending into the internal jugular vein leads to septicemia and septic emboli contributing to the development of necrotic abscesses especially in lungs and other tissues such as liver, bone and joints. In this case report, a previously healthy man with pneumonia and empyema due to F.necrophorum has been presented. A 22 year-old man suffering from sore throat for seven days was admitted to emergency department with ongoing fever and dysphagia for three days. On admission he was already taking amoxicillin clavulanic acid and his complaints were relieved with continuation of therapy to a total of 10 days. However, five days after the cessation of treatment he developed productive cough, fever and generalized myalgia. On physical examination, there were crackles on right lower lung, and chest X-ray revealed pulmonary consolidation on the right middle lobe. Levofloxacin therapy was started based on the diagnosis of pneumonia. While polymorphonuclear leucocytes and intracellular gram-negative bacilli were seen in Gram stained sputum smear, sputum culture was reported as normal flora. Although the patient's status had started to improve with treatment, his condition deteriorated with development of fever and dyspnea. Chest X-ray revealed consolidation, pulmonary infiltrates, pleural effusion and air-fluid level on the right. Meropenem, clarithromycin and linezolid were initiated and a chest tube was inserted with the preliminary diagnosis of necrotizing pneumonia, empyema and type-1 respiratory failure. While there was no growth on bronchoalveolar lavage fluid culture, thoracentesis material inoculated into thioglycolate broth revealed turbidity. Further inoculation onto Schaedler agar which was incubated under anaerobic conditions, yielded growth of catalase negative, indol positive, gram-negative anaerobic bacilli identified as F.necrophorum by BBL Crystal system (Becton Dickinson, USA). The detailed history of the patient revealed that fish bone had stuck in his throat a week ago. Clarithromycin and linezolid were discontinued and he was recovered within six weeks of meropenem treatment. F.necrophorum infection should be considered in the differential diagnosis of persistent head and neck infections with rapidly progressive metastatic necrotic lesions especially in healthy young adults and clindamycin or metranidazol should be added to the treatment protocols. PMID- 22090305 TI - [Sepsis caused by Chryseobacterium indologenes in a patient with hydrocephalus]. AB - Chryseobacterium (formerly Flavobacterium) indologenes, is a non-fermentative gram-negative bacillus which is widely found in the nature, primarily soil and water. Since it can survive in chlorine-treated municipal water supplies, and can colonize the sink basins and tap waters of the hospitals, this bacterium may be a potential infectious agent. Contamination of the medical devices containing water (respirators, intubation tubes, humidifiers, incubators for newborns, etc.) in hospital settings may lead to serious infections especially in patients with predisposing diseases, newborns and immunocompromized patients. In this report, a case of fatal C.indologenes septicemia developed in a newborn with hydrocephalus has been presented. A two-months old male infant was admitted to our hospital with the complaints of failure to suck and lethargy for five days and head enlargement. He was diagnosed as meningitis based on the clinical and laboratory findings of cerebrospinal fluid (CSF) (protein: 572 mg/dl, glucose 9.5 mg/dl, chlorine: 111 mg/dl, and presence of abundant polymorphonuclear leukocytes), and empirical antibiotic treatment (ampicillin/sulbactam and cefotaxime) had been started. Since the computerized tomography of the brain pointed out hydrocephalus, an external shunt was placed for CSF drainage on the second day of hospitalization. A total of five CSF and two blood cultures collected during the hospitalization period were inoculated into pediatric aerobic CSF and blood culture bottles (BacT/ALERT, BioMerieux, France) and incubated for 24-48 hours. The isolated bacteria from all of the cultures were identified as C.indologenes by conventional methods and BD Phoenix (Becton Dickinson, USA) system. Antibiotic susceptibility tests were performed with microdilution method according to CLSI guidelines. The isolate was found susceptible to ciprofloxacin, levofloxacin and trimethoprim/sulfamethoxazole, while it was resistant to amikacin, gentamicin, tobramycin, piperacillin, cefotaxime, ceftazidime, aztreonam, meropenem, imipenem, tetracycline, and chloramphenicol. The treatment continued with ampicillin/sulbactam and levofloxacin without removing the shunt. However, C.indologenes growth persisted in CSF and blood cultures of the patient. The general condition of the patient deteriorated on the 65. day of the hospitalization and the patient was lost due to cardiopulmonary arrest. Case reports related to isolation of C.indologenes from blood cultures are present in the literature, however, isolation of C.indologenes from central nervous system was reported previously in a single case. In conclusion, C.indologenes should be considered as opportunistic infectious agents especially in the infectious diseases that develop in immunocompromised patients with underlying disease and with foreign device implementation. PMID- 22090306 TI - [Meningitis and white matter lesions due to Streptococcus mitis in a previously healthy child]. AB - Streptococcus mitis, an important member of viridans streptococci, is found in the normal flora of the oropharynx, gastrointestinal tract, female genital tract and skin. Although it is of low pathogenicity and virulence, it may cause serious infections in immunocompromised patients. Meningitis caused by S.mitis has been described in patients with previous spinal anesthesia, neurosurgical procedure, malignancy, bacterial endocarditis with neurological complications and alcoholics, but it is rare in patients who are previously healthy. In this report, a rare case of meningoencephalitis caused by S.mitis developed in a previously healthy child has been presented. A previously healthy eight-year-old girl who presented with fever, altered state of consciousness, and headache was hospitalized in intensive care unit with the diagnosis of meningitis. Past history revealed that she was treated with amoxicillin-clavulanate for acute sinusitis ten days before her admission. Whole blood count revealed the followings: hemoglobin 13 g/dl, white blood cell count 18.6 x 109/L (90% neutrophils), platelet count 200 x 109/L and 150 leucocytes were detected on cerebrospinal fluid (CSF) examination. Protein and glucose levels of CSF were 80 mg/dl and 40 mg/dl (concomitant blood glucose 100 mg/dl), respectively. Brain magnetic resonance imaging (MRI) revealed widespread white matter lesions, and alpha-hemolytic streptococci were grown in CSF culture. The isolate was identified as S.mitis with conventional methods, and also confirmed by VITEK2 (bioMerieux, France) and API 20 STREP (bioMerieux, France) systems. Isolate was found susceptible to penicillin, erythromycin, clindamycin, tetracycline, cefotaxime, vancomycin and chloramphenicol. Regarding the etiology, echocardiography revealed no vegetation nor valve pathology, and peripheral blood smear showed no abnormality. Immunoglobulin and complement levels were within normal limits. Ongoing inflammation in maxillary sinuses detected in brain MRI suggested that meningitis could be related to previous sinus infection. After 14 days of ceftriaxone treatment, the patient was discharged from the hospital with cure. The aim of this case presentation was to emphasize that S.mitis may cause meningitis and white matter lesions in previously healthy children with concomitant sinusitis. PMID- 22090307 TI - [Two cases of tick-borne tularemia in Yozgat province, Turkey]. AB - Tularemia which has a worldwide distribution, is a zoonotic infection caused by Francisella tularensis. F.tularensis can infect a wide range of animals and can be transmitted to humans in a variety of ways, the most common being by the bite of an infected arthropod vector (usually tick) in the USA and Europe. The clinical presentations have been classically divided into ulceroglandular, glandular, oculoglandular, pharyngeal, respiratory, and typhoidal tularemia depending on the route of transmission. Arthropod-borne infection generally leads to the ulceroglandular form of tularemia. In Turkey, oropharyngeal form which is related to the consumption of contaminated water, is the most common presentation of tularemia. In this report, two cases of ulceroglandular tularemia which developed as a consequence of tick bite in Yozgat province have been presented. A 33-year-old female patient was admitted to the hospital with a tender lump on the right axilla. Empiric antibiotic treatment with amoxicillin clavulanate did not lead to an improvement in the painful axillary mass. She reported a tick bite on her right shoulder before development of fever, chills and regional tender lump. On physical examination, hyperemia was seen on the shoulder, with enlarged tender right axillary lymph node. The clinical diagnosis of suspected ulceroglandular tularemia was confirmed by the seroconversion (1/160 and 1/1280 titers in acute and convelescent sera, respectively) with microagglutination test (MAT) and F.tularensis DNA positivity in lymph node aspirate by polymerase chain reaction. The agent was identified as F.tularensis subsp. holarctica based on the results of amplification of target RD1 gene. Second case, a 18-year-old male, was admitted to our hospital with a-week history of sudden onset of fever, headache, generalized aches, vomiting, nause, and tender lump on the left axilla. On physical examination, an inflammatory eschar was seen on his scalp with enlarged cervical lymph node on left side. The tick, which has removed from the scalp lesion by the patient himself was identified as Dermacentor spp. The suspected diagnosis of ulceroglandular tularemia was confirmed by 1/2560 titer positivity obtained with MAT. Gentamicin (5 mg/kg/day, PO) was initiated for the treatment of both patients, however, LAP did persist in both of them requiring abscess drainage and prolonged treatment with gentamicin following a 14-day course of ciprofloxacin (1500 mg/day, PO). LAP decreased after medical treatment and repetitive drainage procedures. The patients recovered completely without sequela. These cases, to the best of our knowledge, who were the first confirmed tick-borne tularemia cases in our country, were presented to call attention to a different mode of transmission for F.tularensis. PMID- 22090308 TI - [In vitro activity of daptomycin against methicillin-resistant Staphylococcus aureus strains isolated from blood cultures]. AB - The aim of this study was to detect the in vitro activity of daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from blood cultures at Ataturk Training and Research Hospital, Izmir, Turkey between 2006 2010. A total of 64 MRSA clinical isolates were included in the study, and daptomycin susceptibility were investigated by E-test (AB bioMerieux, Sweden). The identification of the MRSA isolates was based on conventional microbiological methods and an additional automated identification system (Phoenix 100, BD Diagnostic Systems, USA). Etest strips were applied to the surface of Mueller Hinton agar plates and incubated at 35 degrees C in ambient air for 18 to 24 hours. Strains with a MIC value of <= 1 ug/ml were accepted as susceptible to daptomycin. In our study all of the 64 MRSA isolates were found susceptible to daptomycin (MIC <= 1 ug/ml). The MIC50, MIC90 and MIC ranges were detected as 0.125, 0.5 and 0.125-0.5 ug/ml, respectively. Only a single isolate yielded MIC value of 1 ug/ml. As a result daptomycin was found to be very active against MRSA strains in vitro. Our findings suggested that daptomycin might be a suitable alternative agent for treating bacteremia caused by MRSA. However, further large scaled studies and clinical trials are necessary to support these in vitro data. PMID- 22090309 TI - [Evaluation of vancomycin, teicoplanin, linezolide and tigecycline susceptibilities of nosocomial methicillin-resistant Staphylococcus strains by E test]. AB - The aim of this study was to determine the minimal inhibitory concentration (MIC) values of vancomycin, teicoplanin, tigecycline and linezolid in 100 methicillin resistant staphylococci [21 methicillin-resistant Staphylococcus aureus (MRSA) and 79 methicillin-resistant coagulase negative staphylococcus (MR-CNS)] isolated as agents of nosocomial infection from patients at Ankara Training and Research Hospital between June 2005-March 2007. The MIC values for vancomycin, teicoplanin, linezolid and tigecycline were tested by E-test method (AB Biodisk, Sweden). For 21 MRSA strains MIC50 and MIC90 values were as follows: vancomycin 0.125 ug/ml and 1 ug/ml; teicoplanin 0.5 ug/ml and 3 ug/ml, linezolid 0.047 ug/ml and 0.19 ug/ml; tigecycline 0.094 ug/ml and 0.5 ug/ml, respectively. For 79 MR CNS strains MIC50 and MIC90 values were as follows: vancomycin 0.5 ug/ml and 2 ug/ml; teicoplanin 2 ug/ml and 4 ug/ml; linezolid 0.125 ug/ml and 0.25 ug/ml; tigecycline 0.38 ug/ml and 0.5 ug/ml, respectively. No resistance to vancomycin, teicoplanin, tigecycline and linezolid were determined in methicillin-resistant staphylococcus strains isolated from the inpatients in our hospital. Among glycopeptides, MIC50 and MIC90 values of vancomycin were found to be lower than that of teicoplanin. PMID- 22090310 TI - [Evaluation of tularemia cases originated from Central Anatolia, Turkey]. AB - Tularemia is an infection caused by Francisella tularensis with a worldwide distribution and diverse clinical manifestations. In recent years, tularemia cases are increasing in Turkey, with a special attention to Marmara, western Blacksea and Central Anatolia regions. The aim of this study was to evaluate tularemia cases admitted to our hospital during an outbreak emerged at Central Anatolia between December 2009 and September 2010, making a point for the disease. A total of 32 patients (17 female, 15 male; age range: 15-80 years, mean age: 41 +/- 16 years) with fever, sore throat, cervical mass and failure to respond to beta-lactam antibiotics, were followed up with the preliminary diagnosis of tularemia. The diagnosis was confirmed by specific laboratory tests. Serum samples were obtained from 25 patients and in 17 (68%) of them microagglutination test yielded positive result (>= 1/160) in their first serum samples. All of the 8 patients who had negative results in their first samples (< 1/160), revealed seroconversion in their second samples. In 10 (91%) of the 11 patients from whom lymph node aspirates were obtained, PCR performed with species specific (tul4) primers yielded positivity and subspecies differentiation done by RD1 primers identified the agent as F.tularensis subspecies holarctica. F.tularensis growth was not detected in the cultures of lymph aspirates and/or throat swabs of the cases (n= 16). All the patients had oropharyngeal tularemia and eight of them also had oculoglandular form. The mean duration of the symptoms were 25.6 +/- 17.2 (2-60) days. They had a history of oral intake of contaminated water. Cervical or submandibular lymphadenopathy were detected in all patients. One patient had cervical abscess and the other one had erythema nodosum. Elevated sedimentation rate was found in 26 (81.3%) patients and elevated CRP in 24 (75%) patients. Spontaneous drainage was detected in nine cases during follow-up. Lymph node aspiration was performed in patients when fluctuation was detected. Streptomycin 2 g/day for 10 days was given to 21 patients and doxycycline 2 x 100 mg for 14 days was given to 11 patients. Twelve (37.5%) patients received further antibiotic treatment since they failed to respond to the first therapy. Of the patients, 21 recovered completely and two patients had lymph node excision. No severe complications were observed. The patients who applied to the hospital within 10 days of the initiation of the symptoms were treated successfully, while the others that applied later were not. In conclusion, tularemia which is an endemic disease in Turkey, should be kept in mind in patients with fever, sore throat and lymphadenopathy. PMID- 22090311 TI - [Protozoal antigen positivity in diarrheal patients admitted to emergency service: a point prevalence study]. AB - Intestinal parasites are the important etiological agents of water and food related diarrhea cases which are frequently seen during summer/early autumn seasons in developing countries. This point prevalence study was aimed to determine the protozoal antigen positivity rate in diarrhea cases admitted to the emergency service in one single day. A total of 198 diarrheal patients (90 male, 108 female; age range: 1-82 years, mean age: 29 years) who were admitted to the emergency service of Ankara Training and Research Hospital were included in the study. Macroscopic and direct microscopic examinations were performed for the stool samples of patients, and the samples which yielded pathological microscopic findings (e.g. presence of leukocytes, erythrocytes, and trophozoits) were investigated in terms of Entamoeba histolytica adhesin antigen, Giardia intestinalis cyst antigen and Cryptosporidium oocyst antigen by commercial ELISA kits (Techlab, USA). Macroscopic examination of the stool samples revealed that 60 (30%) of them had blood and mucous, 137 (69%) were watery and one sample had normal appearance. Pathologic results were obtained for 96 (48.5%) of the samples by microscopic examination: 36 (37.5%) revealed erythrocytes, 90 (93.7%) had leukocytes and 3 (1.5%) had G.intestinalis trophozoites. Since Shigella spp. were cultured in two of these 96 samples, these two cases were omitted from the study and 94 samples were investigated by ELISA assays. G.intestinalis was detected in 13 (13.8%) and E.histolytica in 2 (2.1%) samples while Cryptosporidium antigen was not detected in any of the samples by the ELISA assays. It was concluded that ELISA antigen assays were rapid and cost-effective methods for the determination of the causative agent in cases of diarrhea. PMID- 22090312 TI - New Agents for Acute Treatment of Migraine: CGRP Receptor Antagonists, iNOS Inhibitors. AB - OPINION STATEMENT: The treatment of migraine was advanced dramatically with the introduction of triptans in the early 1990s. Despite the substantial improvement in the quality of life that triptans have brought to many migraineurs, a substantial cohort of patients remain highly disabled by attacks and need new therapeutic approaches, which ideally should be quick-acting, have no vasoconstrictor activity, and have a longer duration of action and be better tolerated than current therapies. The calcitonin gene-related peptide (CGRP) receptor antagonists (gepants)-olcegepant (BIBN 4096 BS), telcagepant (MK-0974), MK3207, and BI 44370 TA-are effective in treating acute migraine. They have no vasoconstrictive properties, fewer adverse effects, and may act longer than triptans. Their development has been complicated by liver toxicity issues when used as preventives. Results from studies with BI 44370 TA do not support broad concern about a class effect, and further studies are ongoing in this respect. Many experimental studies and clinical trials suggest that nitric oxide may have a role in the pathophysiology of migraine. Therefore, the inhibition of nitric oxide synthase (NOS) for the acute or prophylactic treatment of migraine offered a feasible approach; as inducible NOS (iNOS) is involved in several pain states, such as inflammatory pain, it appeared to be an attractive target. However, despite high selectivity and potency, the iNOS inhibitor GW274150 was not effective for acute treatment or prophylaxis of migraine, suggesting that iNOS is very unlikely to be a promising target. PMID- 22090313 TI - Light-sensitive coupling of rhodopsin and melanopsin to G(i/o) and G(q) signal transduction in Caenorhabditis elegans. AB - Activation of G-protein-coupled receptors (GPCRs) initiates signal transduction cascades that affect many physiological responses. The worm Caenorhabditis elegans expresses >1000 of these receptors along with their cognate heterotrimeric G proteins. Here, we report properties of 9-cis-retinal regenerated bovine opsin [(b)isoRho] and human melanopsin [(h)Mo], two light activated, heterologously expressed GPCRs in the nervous system of C. elegans with various genetically engineered alterations. Profound transient photoactivation of G(i/o) signaling by (b)isoRho led to a sudden and transient loss of worm motility dependent on cyclic adenosine monophosphate, whereas transient photoactivation of G(q) signaling by (h)Mo enhanced worm locomotion dependent on phospholipase Cbeta. These transgenic C. elegans models provide a unique way to study the consequences of G(i/o) and G(q) signaling in vivo with temporal and spatial precision and, by analogy, their relationship to human neuromotor function. PMID- 22090314 TI - Heterologous expression of functional G-protein-coupled receptors in Caenorhabditis elegans. AB - New strategies for expression, purification, functional characterization, and structural determination of membrane-spanning G-protein-coupled receptors (GPCRs) are constantly being developed because of their importance to human health. Here, we report a Caenorhabditis elegans heterologous expression system able to produce milligram amounts of functional native and engineered GPCRs. Both bovine opsin [(b)opsin] and human adenosine A(2A) subtype receptor [(h)A(2A)R] expressed in neurons or muscles of C. elegans were localized to cell membranes. Worms expressing these GPCRs manifested changes in motor behavior in response to light and ligands, respectively. With a newly devised protocol, 0.6-1 mg of purified homogenous 9-cis-retinal-bound bovine isorhodopsin [(b)isoRho] and ligand-bound (h)A(2A)R were obtained from C. elegans from one 10-L fermentation at low cost. Purified recombinant (b)isoRho exhibited its signature absorbance spectrum and activated its cognate G-protein transducin in vitro at a rate similar to native rhodopsin (Rho) obtained from bovine retina. Generally high expression levels of 11 native and mutant GPCRs demonstrated the potential of this C. elegans system to produce milligram quantities of high-quality GPCRs and possibly other membrane proteins suitable for detailed characterization. PMID- 22090315 TI - Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves. AB - Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses. PMID- 22090317 TI - Discontinuous LYVE-1 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots. AB - LYVE-1(+) corneal lymphatics contribute to drainage and immunity. LYVE-1 is widely accepted as the most reliable lymphatic marker because of its continuous expression in lymphatic endothelium. LYVE-1 expression in corneal lymphatics has not been examined. In this study, we report intact CD31(+) corneal lymphatic capillary endothelial cells that do not express LYVE-1. The number of LYVE-1(-) gaps initially increased until 8 wk of age but was significantly reduced in aged mice. C57BL/6 mice showed a notably higher number of the LYVE-1(-)/CD31(+) lymphatic regions than BALB/c mice, which suggests a genetic predisposition for this histological feature. The LYVE-1(-) lymphatic gaps expressed podoplanin and VE-cadherin but not alphaSMA or FOXC2. Interestingly, the number of LYVE-1(-) gaps in FGF-2, but not VEGF-A, implanted corneas was significantly lower than in untreated corneas. Over 70% of the CD45(+) leukocytes were found in the proximity of the LYVE-1(-) gaps. Using a novel in vivo imaging technique for visualization of leukocyte migration into and out of corneal stroma, we showed reentry of extravasated leukocytes from angiogenic vessels into newly grown corneal lymphatics. This process was inhibited by VE-cadherin blockade. To date, existence of lymphatic valves in cornea is unknown. Electron microscopy showed overlapping lymphatic endothelial ends, reminiscent of microvalves in corneal lymphatics. This work introduces a novel corneal endothelial lymphatic phenotype that lacks LYVE-1. LYVE-1(-) lymphatic endothelium could serve as microvalves, supporting unidirectional flow, as well as immunological hot spots that facilitate reentry of stromal macropahges. PMID- 22090318 TI - Antimicrobial de-escalation in cancer patients. PMID- 22090316 TI - Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes. AB - Recent studies indicate that members of the multidrug-resistance protein (MRP) family belonging to ATP binding cassette type C (ABCC) membrane proteins extrude cyclic nucleotides from various cell types. This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we demonstrate that MRP4 is the predominant isoform present at the plasma membrane of cardiacmyocytes and that it mediates the efflux of cAMP in these cells. MRP4-deficient mice displayed enhanced cardiac myocyte cAMP formation, contractility, and cardiac hypertrophy at 9 mo of age, an effect that was compensated transiently by increased phosphodiesterase expression at young age. These findings suggest that cAMP extrusion via MRP4 acts together with phosphodiesterases to control cAMP levels in cardiac myocytes. PMID- 22090320 TI - Prevention of adhesion to prosthetic mesh: comparison of oxidized generated cellulose, polyethylene glycol and hylan G-F 20. AB - BACKGROUND: The aim of this study was to investigate the impact of oxidized generated cellulose, polyethylene glycol and hylan G-F 20 on adhesion formation, fibrosis and inflammation after repair of abdominal wall defect with polypropylene mesh in an animal model. METHODS: Forty rats were divided into four groups and abdominal wall defect was established. The defect was repaired with polypropylene mesh alone (control group), polypropylene mesh and hylan G-F 20 as adhesion barrier, polypropylene mesh and oxidized generated cellulose as adhesion barrier, or polypropylene mesh and polyethylene glycol as adhesion barrier in Groups I, II, III, and IV, respectively. Rats were sacrificed on the 14th day in all groups. RESULTS: A comparison of the groups in terms of macroscopic adhesion scores revealed statistically significant differences between the groups using an adhesion barrier and the control group. Severe fibroblast proliferation was seen in the control group and mild fibroblast proliferation was seen in polyethylene glycol group. CONCLUSION: Polyethylene glycol is an effective adhesion prevention barrier. Laparoscopic surgery has become the standard method in most of the surgical field. With its laparoscopic apparatus, polyethylene glycol allows easy application on the damaged surface. PMID- 22090321 TI - Beneficial effects of alpha lipoic acid on cerulein-induced experimental acute pancreatitis in rats. AB - BACKGROUND: The present study aimed to determine the effects of alpha lipoic acid (ALA) on blood and tissue biochemical parameters, as well as tissue histopathology, in an experimental rat model of cerulein-induced acute pancreatitis (AP). METHODS: Three groups consisting of eight rats each were used, as follows: Group 1, controls; Group 2, cerulein-induced pancreatitis group treated with saline; and Group 3, cerulein-induced pancreatitis group treated with ALA. AP was induced by intraperitoneal administration of cerulein (20 ug/kg) 4 times at 1-hour intervals. The animals were decapitated 12 hours after the last dose of cerulein. Blood amylase, lipase, interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha levels, pancreas tissue glutathione (GSH) and malondialdehyde (MDA) levels, as well as myeloperoxidase (MPO) and Na+-K+-ATPase activity were measured. Pancreatic tissue samples were also evaluated histopathologically under a light microscope. RESULTS: While plasma amylase, lipase, IL-1beta, and TNF-alpha levels, and tissue MDA and MPO levels significantly increased in rats with cerulean-induced AP, tissue GSH and Na+-K+ ATPase activity significantly reduced. These changes were reversed and improved with ALA treatment. CONCLUSION: Our findings suggest that ALA may significantly reduce morbidity and mortality by preventing organ dysfunction induced by free radicals in the pancreas. PMID- 22090322 TI - The value of CRP, IL-6, leptin, cortisol, and peritoneal caspase-3 monitoring in the operative strategy of secondary peritonitis. AB - BACKGROUND: We aimed to investigate the impact of C-reactive protein (CRP), interleukin (IL)-6, leptin, cortisol, and caspase-3 on the decision of terminating planned abdominal repair in secondary peritonitis. METHODS: Fifteen patients with peritonitis were enrolled into the study. Serum CRP, IL-6, leptin, cortisol, and peritoneal caspase-3 activities were measured. RESULTS: APACHE II scores at 48 hours (h) and age were significantly higher in non-survivors. A significant decrease was observed in caspase-3 activities of patients in whom <=4 laparotomies were performed when compared with those who underwent >4 laparotomies. For patients who underwent <=4 laparotomies, there was a significant difference in caspase-3 levels between 0 and 72 h. There was no significant difference in caspase-3 levels in non-survivors; caspase-3 levels were significantly lower in the survivors at 48 and 72 h. Changes in CRP, IL-6, leptin, and cortisol levels were not statistically significant. CONCLUSION: CRP, IL-6, leptin, cortisol, and caspase-3 are not valuable in discriminating the number of planned operations, even though there is a significant decrease in caspase-3 "within" survivors. The discriminative value of caspase-3 for closure should be evaluated in studies in which caspase-3 is monitored for a longer duration in a large number of patients. PMID- 22090323 TI - Scoring systems in the diagnosis of acute appendicitis in the elderly. AB - BACKGROUND: Although special features of acute appendicitis in the elderly have been described in some studies, no studies evaluating the applicability of appendicitis scores exist in the literature. The aim of this study was to compare Alvarado and Lintula scores in patients older than 65 years of age. METHODS: Patients older than 65 years with appendicitis confirmed by pathology report were matched by year of admission with a group of patients admitted to the emergency department with non-specific abdominal pain. Alvarado and Lintula scores were calculated retrospectively from patient charts. RESULTS: Both scores were observed to operate well in distinguishing between abdominal pain due to appendicitis and non-specific abdominal pain. The Alvarado score was a better predictor compared to the Lintula score. Two parameters (absent, tingling or high pitched bowel sounds and nausea) had similar prevalence in the control and appendicitis groups. We selected to recalculate the two scores with the exclusion of these two parameters. The two scores performed better but were more similar to each other after the modification. CONCLUSION: Both Alvarado and Lintula scores have a high sensitivity and specificity in the diagnosis of acute appendicitis in the geriatric age group. Their performance improves with exclusion of the two parameters "nausea" and "absent, tingling or high-pitched bowel sounds". PMID- 22090324 TI - Factors affecting morbidity in penetrating rectal injuries: a civilian experience. AB - BACKGROUND: The principles of the treatment of rectal injuries have been determined based on the experiences gained from military injuries. While adopting these principles in civilian life, it is essential to know the characteristics of civilian rectal injuries as well as the risk factors affecting morbidity. METHODS: The characteristics of 29 inpatients who had been treated due to rectal injuries caused by gunshot wounds and penetrating devices were evaluated. In order to determine the risk factors, the patients were divided into two groups regarding the presence of morbidity (Group 1, with morbidity; Group 2, without morbidity) and compared. RESULTS: Severe fecal contamination, perianal or gluteal injuries, duration of trauma- treatment interval, and isolated extraperitoneal injury were significant factors that affected the development of morbidity. The length of hospital stay was significantly longer in Group 1 as compared to Group 2. CONCLUSION: Although rectal injuries are rarely encountered, they carry high morbidity and mortality. Awareness of the risk factors and planning of a patient based treatment are essential for the success of the therapy. The rate of morbidity is substantially decreased when patients are treated in time. Thus, the awareness of both patients as well as physicians managing trauma about rectal injuries should be increased. PMID- 22090325 TI - The use of Ender nail in intertrochanteric fractures supported with external fixation. AB - BACKGROUND: Intramedullary Ender nailing in intertrochanteric fractures was very popular in the past. However, this method has fallen in favor over time, due to complications. The purpose of this study was to evaluate results with this method and possible ways to prevent these complications, including the use of unilateral fixators to support the Ender nails. METHODS: This technique (Ender nailing and external fixator) was used in 39 patients (17 M/22 F, mean age: 71.4 years). The preoperative mean American Society of Anesthesiologists (ASA) score was 1.84 (range: 1-4) for all the patients. AO/OTA classification of fractures was used. In our surgery, we used an external fixator to support the intramedullary nails. All patients were evaluated with Parker-Palmer mobility score and with the Harris hip score. RESULTS: The follow-up period was 29.2 months (20-56). Two patients experienced nail migration in the knees, two patients had varus deformation with a reduction in length of 2 cm, and seven patients developed pin-track infection. The average Harris score and Parker-Palmer score of the 14 patients who presented for their last follow-up examination were 64 and 6.8, respectively. CONCLUSION: This method demonstrated several advantages, in that it allows the patient to put weight on the extremity after a shorter period of time and enables the fracture to heal rapidly without any serious complications. PMID- 22090326 TI - Characteristics of open globe injuries in geriatric patients. AB - BACKGROUND: We aimed to evaluate the etiological and demographic characteristics of open globe injuries in geriatric patients, to determine the factors affecting the prognosis and to discuss the differences between geriatric and young populations in light of the current literature. METHODS: The medical files of 30 patients aged 65 years and older who were treated and followed up for open globe injuries between 1998 and 2009 were evaluated retrospectively. RESULTS: The mean age was 73.1 years. Sixty percent of the patients were male, with a predominance of left eye involvement. The most common type of trauma was rupture due to a blunt object. The presenting visual acuity was no light perception in 13 patients, light perception/hand movement in 15 patients and 1/200-19/200 in 2 patients. In a univariate analysis assessing the effects of demographic and clinical characteristics on final vision, the wound location, type of trauma and Ocular Trauma Score were found to be statistically significant variations. CONCLUSION: The prognosis of open globe injuries is very poor in geriatric patients. Age-related structural changes and previous history of surgeries contribute to easy development of a rupture. During the treatment process, limited recovery capacity, ocular pathology in patients and low functional capacity in this age group exert negative effects on the prognosis. PMID- 22090327 TI - Hot milk burns in children: a crucial issue among 764 scaldings. AB - BACKGROUND: Burns are among the preventable traumas encountered during childhood. Burn injuries are mostly classified as scalds, flame, electric, and chemical burns. However, each subject has some difference in the course of treatment related to the sub-etiologies. To reveal the importance of milk burns, scald burn patients were studied retrospectively. METHODS: Demographics of the patients, burn etiologies, clinical presentations, and clinical courses were analyzed. There were 461 (60.4%) male and 303 (39.6%) female patients, with a 1.52 male to female ratio. RESULTS: The mean age of the group was 3.36+/-2.86 years. There were no difference in burn causes between males and females. The mean burned total body surface area of patients was 16.91+/-12.63%. Hot milk caused larger, deeper burns than the other scalds and caused more third-degree burns (p<0.001, p<0.001, p<0.05, respectively). Milk burns also resulted in longer hospital stay (days) (p<0.001). The mortality rate was also higher in milk burns than other scalds (p<0.001). CONCLUSION: Due to the more detrimental clinical course, milk burns necessitate special consideration in clinical settings. The most important factor is to be aware that burns are deeper than they appear. PMID- 22090328 TI - Cardiac and great vessel injuries after chest trauma: our 10-year experience. AB - BACKGROUND: Cardiovascular injuries after trauma present with high mortality. The aim of the study was to present our experience in cardiac and great vessel injuries after chest trauma. METHODS: During the 10-year period, 104 patients with cardiac (n=94) and great vessel (n=10) injuries presented to our hospital. The demographic data, mechanism of injury, location of injury, other associated injuries, timing of surgical intervention, surgical approach, and clinical outcome were reviewed. RESULTS: Eighty-eight (84.6%) males presented after chest trauma. The mean age of the patients was 32.5+/-8.2 years (range: 12-76). Penetrating injuries (62.5%) were the most common cause of trauma. Computed tomography was performed in most cases and echocardiography was used in some stable cases. Cardiac injuries mostly included the right ventricle (58.5%). Great vessel injuries involved the subclavian vein in 6, innominate vein in 1, vena cava in 1, and descending aorta in 2 patients. Early operations after admission to the emergency were performed in 75.9% of the patients. Thoracotomy was performed in 89.5% of the patients. Operative mortality was significantly high in penetrating injuries (p=0.01). CONCLUSION: Clinicians should suspect cardiac and great vessel trauma in every patient presenting to the emergency unit after chest trauma. Computed tomography and echocardiography are beneficial in the management of chest trauma. Operative timing depends on hemodynamic status, and a multidisciplinary team approach improves the patient's prognosis. PMID- 22090329 TI - Still an unknown topic: child abuse and "shaken baby syndrome". AB - BACKGROUND: Shaken baby syndrome (SBS) is a severe form of physical child abuse, and can even cause death. In this study, we aimed to investigate whether or not the primary healthcare workers had received any education regarding child abuse and neglect, whether they could diagnose the cases, whether they had sufficient knowledge about SBS as a part of child abuse, and whether they were in need of education on the topic. METHODS: Health workers in the primary healthcare centers in the province of Kayseri were enrolled. A questionnaire was applied. RESULTS: In this study, 35.0% of the study group were physicians. 43.7% of the study group stated that they had not recieved any education regarding child abuse and neglect, and 52.1% stated that they believed that physical abuse was the most prominent form of abuse in society. While 64.1% of the participants stated that they had heard about SBS, 10.4% of these stated that they had heard about it, but did not have adequate knowledge on the topic. CONCLUSION: There is a lack of knowledge and a need for education regarding child abuse and neglect among the personnel working in primary healthcare, especially on the subject of SBS. Undergraduate and postgraduate education regarding child abuse and SBS will help to increase the number of people well-informed and sensitive to this important issue. PMID- 22090330 TI - Delayed presentation of posttraumatic diaphragmatic hernia. AB - BACKGROUND: Missed diaphragmatic injuries after trauma may present with herniation of intraabdominal organs into the thoracic cavity. We aimed to review our patients who presented with delayed posttraumatic diaphragmatic hernia. METHODS: A retrospective review of the medical records of patients with delayed diagnosis of posttraumatic diaphragmatic hernia between 2001 and 2009 was performed. RESULTS: Ten patients with a mean age of 44.3 years were included. Six patients were female. Blunt injuries (n: 7) were more common. Mean duration between trauma and presentation to the hospital was 5.9 years (4 months - 19 years). Nine patients had left-sided diaphragmatic hernia. All patients had chest X-ray and most were diagnostic (n: 8). Additional diagnostic imaging with computerized tomography (CT) and magnetic resonance (MR) was used in seven patients. For the repair, laparotomy incision was chosen for seven patients and thoracotomy incision for two patients. One patient underwent left thoracoabdominal approach. Mesh repair was used in seven patients. Postoperative mean hospitalization was 10.6 days. Empyema and atelectasis were the morbidities in one patient. No postoperative mortality was detected. CONCLUSION: Delayed presentation of posttraumatic diaphragmatic hernia is a serious challenge for trauma surgeons. Prompt diagnosis and treatment prevent serious morbidity and mortality associated with complications such as gangrene and/or perforation of the herniated organ. PMID- 22090331 TI - 10-year evaluation of train accidents. AB - BACKGROUND: Although less frequent than automobile accidents, train accidents have a major impact on victims' lives. METHODS: Records of patients older than 16 years of age admitted to the Adult Emergency Department of Hacettepe University Medical Center due to train accidents were retrospectively evaluated. RESULTS: 44 patients (30 males, 14 females) with a mean age of 31.8+/-11.4 years were included in the study. The majority of the accidents occurred during commuting hours. 37 patients were discharged, 22 of them from the emergency department. The mortality rate was 7/44 (16%). Overall mean Revised Trauma Score (RTS) was 10.5 (3 in deaths and 11.9 in survivors). In 5 patients, the cause of death was pelvic trauma leading to major vascular injury and lower limb amputation. In 1 patient, thorax and abdomen trauma and in 1 patient head injury were the causes of mortality. Primary risk factors for mortality were alcohol intoxication (100%), cardiopulmonary resuscitation on admittance (100%), recurrent suicide attempt (75%), presence of psychiatric illness (60%), and low RTS. CONCLUSION: In this study, most train accidents causing minor injuries were due to falling from the train prior to acceleration. Nevertheless, train accidents led to a mortality rate of 16% and morbidity rate of 37%. These findings draw attention to the importance of developing preventive strategies. PMID- 22090332 TI - [Domestic accidents involving women and first aid knowledge]. AB - BACKGROUND: Domestic accidents (DA) are preventable and untoward events occurring in a house, pool or garage. Those events constitute a major issue in the context of public health. The objective of this study was to highlight the characteristics of female involvement in DA and their level of knowledge regarding first aid. METHODS: Adult female relatives of patients presenting at the university-based emergency department within the six-month study period comprised the study sample. They were asked to answer a 23-item self-reported questionnaire, and the responses were analyzed. RESULTS: A total of 1017 women (mean age: 29.2+/-11.1 years) were enrolled in the study. Hand lacerations (n=924, 90.8%), sprain and contusions (n=904, 88.8%) and burns (n=803, 78.9%) were the most commonly reported types of DA. The children were reported to suffer mostly from hits, sprains and contusions (n=478, 91.7%), followed by falls and slipping (n=452, 86.7%). The telephone number of emergency medical services was recalled most frequently (n=871, 85.6%), while that of the poison control center was known least commonly (n=48, 4.7%). The group with the highest level of education had a significantly higher mean number of correct answers than that of the group with the lowest level of education (p=0.001). The knowledge level of the women who worked was significantly lower than that of the unemployed women (p=0.02). CONCLUSION: Extensive training of women on DA should be undertaken and the mass media should be utilized to achieve this goal. PMID- 22090333 TI - [The affecting factors on the complication ratio in abdominal gunshot wounds]. AB - BACKGROUND: We aimed to investigate the affecting factors on the complication ratio in abdominal gunshot wounds. METHODS: Twenty-one patients with abdominal gunshot wounds were analyzed between February 2002 and May 2005. The effects of the interval between trauma and presentation to the hospital, the number of injured abdominal and extra-abdominal organs, penetrating abdominal trauma index (PATI), and blood transfusion were evaluated. RESULTS: 90.4% of all patients were transported to the hospital and underwent their first evaluation in the first two hours. The complication rate was 7.1% in patients who had <3 injured organs and 71% in the others (p<0.0001). 71.4% of the patients had isolated abdominal trauma, while 28.6% had additional extra-abdominal organ trauma. The complication rate was 7.7% in 13 patients with PATI score <25 and 62.5% in 8 patients with a PATI score >=25 (p<0.0001). In 10 patients who underwent blood transfusion of >=3 units, the complication rate was 50% (p<0.0001). CONCLUSION: In our study, PATI score, multiple blood transfusions and the number of injured intra-abdominal organs were the most important factors affecting the rate of postoperative complications in penetrating abdominal gunshot wounds. We found that the interval between trauma and presentation to the hospital and number of injured extra abdominal organs did not affect the complication rate. PMID- 22090334 TI - Masked urinary bladder injury with a bullet expulsed spontaneously during voiding. AB - We report a case with gunshot to the pelvis. The injury site was the soft tissue between the rectum and urinary bladder. Several days later, the bullet was expulsed spontaneously during voiding. In the literature, only a few case reports have described spontaneous expulsion of an intravesical bullet. A 19-year-old male was wounded on the left hip by gunshot. Radiographic examinations showed a bullet in the pelvis, which was localized in the soft tissue between the rectum and urinary bladder, with no accompanying visceral injury on abdominopelvic computerized tomography. Macroscopic hematuria was noticed after urethral catheterization. Rectosigmoidoscopy and retrograde cystoscopic examinations were both negative. The patient was monitored closely and treated conservatively with no surgical intervention. The urinary catheter was removed on the fifth postoperative day, and the bullet was expulsed spontaneously via the urethra during normal voiding three hours after catheter removal. Thereafter, a retrograde urethrography was performed, which showed no evidence of urinary tract or bladder injury. PMID- 22090335 TI - Spondylolisthesis mimicking the progression of dissection in a case of chronic Stanford type B aortic dissection. AB - Aortic dissection is an acute lethal cardiovascular condition. A 67-year-old hypertensive woman was admitted to our Emergency Department with an abrupt onset of tearing pain in the interscapular area. A thoracic computed tomography scan with contrast showed chronic type B aortic dissection. The patient was transferred to intensive care and medical therapy was initiated. Upon spread of the pain to the lumbar area, the dissection was thought to have progressed. The patient, being hemodynamically stable, was examined using ultrasonography, and the dissection did not show any progression. In the neurological examination for the lumbar pain, the lumbar processus spinosus was found to be sensitive, and the sciatic nerve stretch test was positive at 30 degrees. Magnetic resonance imaging revealed spondylolisthesis and a centrally located disc herniation at the L3-4 level. No operation for the dissection was planned, but discectomy and fusion surgery was scheduled. Since the patient refused surgery, she was discharged with medical therapy. Our aim in this report was to emphasize the importance of spondylolisthesis mimicking the progression of dissection in the differential diagnosis of a chronic type B aortic dissection case. PMID- 22090336 TI - Multidetector computed tomography diagnosis of ileal and antropyloric gallstone ileus. AB - Gallstone-induced ileus is a rare complication of cholelithiasis, and gastric outlet obstruction is even rarer. We describe the multidetector computed tomographic diagnosis of small bowel obstruction resulting from a gallstone impacted in the distal ileum and of gastric outlet obstruction from a gallstone impacted in the pyloric antrum (Bouveret syndrome). PMID- 22090337 TI - Gunshot injury to the penis in a patient with penile prosthesis: a case report. AB - Civilian penetrating injuries to the penis are quite rare. We present the case of a 48-year-old man with prosthetic implant surgery who referred to the emergency department of our clinic with penetrating gunshot injury to the penis. The damaged implant was removed and the defect on the anterior urethra was repaired primarily. To the best of our knowledge, there is no such report in the literature regarding penile gunshot injury in a patient with penile prosthesis. PMID- 22090338 TI - Inflamed vermiform appendix within the sac of incarcerated left inguinal hernia. AB - A 54-year-old male complained of a continuous pain together with an irreducible swelling of the left inguinal region 8 hours prior to admission to the surgical emergency department. His physical examination revealed a very painful, erythematous, irreducible swelling in the left inguinal region without abdominal peritoneal irritation. Routine blood tests disclosed mild leukocytosis. Abdominal plain X-ray film was not specific, and ultrasonography revealed a 10 cm in length inactive, edematous intestinal section within the inguinal hernia. With the diagnosis of strangulated inguinal hernia, he underwent surgical exploration through a transverse inguinal incision. By opening the hernia sac, 6-8 cc inflammatory fluid drained out, and an inflamed vermiform appendix adhered to the inner surface of the sac was seen. Appendicectomy and primary hernia repair were performed at the same time through the inguinal incision. The postoperative course was uneventful, and the histological examination of the specimen revealed an inflamed appendix. PMID- 22090339 TI - Late recognized nail aspiration in a child: case report. AB - Foreign body (FB) aspiration is common in children aged 0-3 years. Our case, a 2.5-year-old girl, presented with sudden onset of cough, fever and sputum; she had been treated twice for acute bronchitis four months ago. Resisting complaints led to an esophagoscopic examination in our Chest Surgery Clinic after a chest X ray suggested FB in the esophagus, but no FB could be detected. A lateral chest X ray revealed a FB with its sharp end targeting the trachea and its round end to the right hemithorax. Removal of the FB with forceps was not possible during rigid bronchoscopy. The FB was removed by thoracotomy and bronchotomy under general anesthesia. The removed FB was a nail measuring 6 cm in length. This case report should serve to stress the diversity of FB aspirations in childhood, the role of parental neglect, and that physicians should be aware of the possibility of FB in children with persistent cough. PMID- 22090340 TI - Royal College of Pathologists' autopsy guidelines on sudden cardiac death: roles for cannabis, cotinine, NSAIDs and psychology. PMID- 22090341 TI - Intraoperative analysis of sentinel lymph nodes in breast cancer by one-step nucleic acid amplification. AB - One-step nucleic acid amplification (OSNA) is a novel method introduced for the lymph node staging of breast cancer and has been tested in multiple series. The present review summarises current literature and concerns related to the new method. The results of this automated molecular assay based on the quantification of cytokeratin 19 mRNA show a 96% concordance rate with detailed histopathology complemented with immunohistochemistry when alternative slices of the same lymph node are used for the two tests. The low false-negative rate makes OSNA suitable for the intraoperative evaluation of sentinel lymph nodes. The false-positive rate also seems very low. Most discordant cases are explainable by low volume metastases (micrometastases), which may be missing from the material submitted for one test, but not from the different part used for the other test. It is tempting to change the gold standard for comparisons between the methods, and if this is done, histology seems to come out as a weaker test for the identification of metastases. OSNA detects more low volume nodal involvement, but it is uncertain whether these require further axillary treatment, and this will be a subject for future investigations. Therefore, it is also uncertain whether the advantage of OSNA of detecting practically all metastases due to complete sampling of lymph node tissue is clinically more important than the exclusion of metastases greater than micrometastasis that can be reliably done by intraoperative microscopy followed by permanent section histology. PMID- 22090342 TI - Nanoethics and the breaching of boundaries: a heuristic for going from encouragement to a fuller integration of ethical, legal and social issues and science : commentary on: "Adding to the mix: integrating ELSI into a National Nanoscale Science and Technology Center". AB - The intersection of ELSI and science forms a complicated nexus yet their integration is an important goal both for society and for the successful advancement of science. In what follows, I present a heuristic that makes boundary identification and crossing an important tool in the discovery of potential areas of ethical, legal, and social concern in science. A dynamic and iterative application of the heuristic can lead towards a fuller integration and appreciation of the concerns of ELSI and of science from both sides of the divide. PMID- 22090343 TI - Spindle assembly requires complete disassembly of spindle remnants from the previous cell cycle. AB - Incomplete mitotic spindle disassembly causes lethality in budding yeast. To determine why spindle disassembly is required for cell viability, we used live cell microscopy to analyze a double mutant strain containing a conditional mutant and a deletion mutant compromised for the kinesin-8 and anaphase-promoting complex-driven spindle-disassembly pathways (td-kip3 and doc1Delta, respectively). Under nonpermissive conditions, spindles in td-kip3 doc1Delta cells could break apart but could not disassemble completely. These cells could exit mitosis and undergo cell division. However, the daughter cells could not assemble functional, bipolar spindles in the ensuing mitosis. During the formation of these dysfunctional spindles, centrosome duplication and separation, as well as recruitment of key midzone-stabilizing proteins all appeared normal, but microtubule polymerization was nevertheless impaired and these spindles often collapsed. Introduction of free tubulin through episomal expression of alpha- and beta-tubulin or introduction of a brief pulse of the microtubule-depolymerizing drug nocodazole allowed spindle assembly in these td-kip3 doc1Delta mutants. Therefore we propose that spindle disassembly is essential for regeneration of the intracellular pool of assembly-competent tubulin required for efficient spindle assembly during subsequent mitoses of daughter cells. PMID- 22090344 TI - YPR139c/LOA1 encodes a novel lysophosphatidic acid acyltransferase associated with lipid droplets and involved in TAG homeostasis. AB - For many years, lipid droplets (LDs) were considered to be an inert store of lipids. However, recent data showed that LDs are dynamic organelles playing an important role in storage and mobilization of neutral lipids. In this paper, we report the characterization of LOA1 (alias VPS66, alias YPR139c), a yeast member of the glycerolipid acyltransferase family. LOA1 mutants show abnormalities in LD morphology. As previously reported, cells lacking LOA1 contain more LDs. Conversely, we showed that overexpression results in fewer LDs. We then compared the lipidome of loa1Delta mutant and wild-type strains. Steady-state metabolic labeling of loa1Delta revealed a significant reduction in triacylglycerol content, while phospholipid (PL) composition remained unchanged. Interestingly, lipidomic analysis indicates that both PLs and glycerolipids are qualitatively affected by the mutation, suggesting that Loa1p is a lysophosphatidic acid acyltransferase (LPA AT) with a preference for oleoyl-CoA. This hypothesis was tested by in vitro assays using both membranes of Escherichia coli cells expressing LOA1 and purified proteins as enzyme sources. Our results from purification of subcellular compartments and proteomic studies show that Loa1p is associated with LD and active in this compartment. Loa1p is therefore a novel LPA AT and plays a role in LD formation. PMID- 22090345 TI - Cdc28 provides a molecular link between Hsp90, morphogenesis, and cell cycle progression in Candida albicans. AB - The trimorphic fungus Candida albicans is the leading cause of systemic candidiasis, a disease with poor prognosis affecting immunocompromised individuals. The capacity of C. albicans to transition between morphological states is a key determinant of its ability to cause life-threatening infection. Recently the molecular chaperone heat shock protein 90 (Hsp90) was implicated as a major regulator of temperature-dependent C. albicans morphogenesis; compromising Hsp90 function induces filamentation and relieves repression of Ras1 protein kinase A (PKA) signaling, although the mechanism involved remains unknown. Here we demonstrate that filaments generated by compromise of Hsp90 function are neither pseudohyphae nor hyphae but closely resemble filaments formed in response to cell cycle arrest. Closer examination revealed that these filaments exhibit a delay in mitotic exit mediated by the checkpoint protein Bub2. Furthermore, Hsp90 inhibition also led to a distinct morphology with defects in cytokinesis. We found that the cyclin-dependent kinase Cdc28 was destabilized in response to depletion of Hsp90 and that Cdc28 physically interacts with Hsp90, implicating this major cell cycle regulator as a novel Hsp90 client protein in C. albicans. Taken together, our results suggest that Hsp90 is instrumental in the regulation of cell division during yeast-form growth in C. albicans and exerts its major effects during late cell cycle events. PMID- 22090346 TI - RNA-related nuclear functions of human Pat1b, the P-body mRNA decay factor. AB - The evolutionarily conserved Pat1 proteins are P-body components recently shown to play important roles in cytoplasmic gene expression control. Using human cell lines, we demonstrate that human Pat1b is a shuttling protein whose nuclear export is mediated via a consensus NES sequence and Crm1, as evidenced by leptomycin B (LMB) treatment. However, not all P-body components are nucleocytoplasmic proteins; rck/p54, Dcp1a, Edc3, Ge-1, and Xrn1 are insensitive to LMB and remain cytoplasmic in its presence. Nuclear Pat1b localizes to PML associated foci and SC35-containing splicing speckles in a transcription dependent manner, whereas in the absence of RNA synthesis, Pat1b redistributes to crescent-shaped nucleolar caps. Furthermore, inhibition of splicing by spliceostatin A leads to the reorganization of SC35 speckles, which is closely mirrored by Pat1b, indicating that it may also be involved in splicing processes. Of interest, Pat1b retention in these three nuclear compartments is mediated via distinct regions of the protein. Examination of the nuclear distribution of 4E T(ransporter), an additional P-body nucleocytoplasmic protein, revealed that 4E-T colocalizes with Pat1b in PML-associated foci but not in nucleolar caps. Taken together, our findings strongly suggest that Pat1b participates in several RNA related nuclear processes in addition to its multiple regulatory roles in the cytoplasm. PMID- 22090347 TI - The cytoskeletal mechanisms of cell-cell junction formation in endothelial cells. AB - The actin cytoskeleton and associated proteins play a vital role in cell-cell adhesion. However, the procedure by which cells establish adherens junctions remains unclear. We investigated the dynamics of cell-cell junction formation and the corresponding architecture of the underlying cytoskeleton in cultured human umbilical vein endothelial cells. We show that the initial interaction between cells is mediated by protruding lamellipodia. On their retraction, cells maintain contact through thin bridges formed by filopodia-like protrusions connected by VE cadherin-rich junctions. Bridges share multiple features with conventional filopodia, such as an internal actin bundle associated with fascin along the length and vasodilator-stimulated phosphoprotein at the tip. It is striking that, unlike conventional filopodia, transformation of actin organization from the lamellipodial network to filopodial bundle during bridge formation occurs in a proximal-to-distal direction and is accompanied by recruitment of fascin in the same direction. Subsequently, bridge bundles recruit nonmuscle myosin II and mature into stress fibers. Myosin II activity is important for bridge formation and accumulation of VE-cadherin in nascent adherens junctions. Our data reveal a mechanism of cell-cell junction formation in endothelial cells using lamellipodia as the initial protrusive contact, subsequently transforming into filopodia-like bridges connected through adherens junctions. Moreover, a novel lamellipodia-to filopodia transition is used in this context. PMID- 22090348 TI - Characterization of NE81, the first lamin-like nucleoskeleton protein in a unicellular organism. AB - Lamins build the nuclear lamina and are required for chromatin organization, gene expression, cell cycle progression, and mechanical stabilization. Despite these universal functions, lamins have so far been found only in metazoans. We have identified protein NE81 in Dictyostelium, which has properties that justify its denomination as a lamin-like protein in a lower eukaryote. This is based on its primary structure, subcellular localization, and regulation during mitosis, and its requirement of the C-terminal CaaX box as a posttranslational processing signal for proper localization. Our knockout and overexpression mutants revealed an important role for NE81 in nuclear integrity, chromatin organization, and mechanical stability of cells. All our results are in agreement with a role for NE81 in formation of a nuclear lamina. This function is corroborated by localization of Dictyostelium NE81 at the nuclear envelope in human cells. The discovery of a lamin-like protein in a unicellular organism is not only intriguing in light of evolution, it may also provide a simple experimental platform for studies of the molecular basis of laminopathies. PMID- 22090349 TI - Using biomaterials to improve the efficacy of cell therapy following acute myocardial infarction. AB - Cardiovascular cell therapy has the potential to improve left ventricular (LV) function and alter the course of adverse LV remodeling following acute myocardial infarction (AMI). However, current therapy using autologous intracoronary bone marrow mononuclear cells results in only minimal recovery of LV function. A major impediment appears to be limited retention and engraftment of the transplanted cells, in part due to loss of the extracellular matrix (ECM) following AMI that can lead to apoptosis of the delivered cells through the mechanism of anoikis. Recent pre-clinical studies suggest that the delivery of ECM surrogates to the infarct zone following AMI significantly improves LV function through multiple mechanisms. The use of ECM surrogates in conjunction with stem cell administration may represent a new paradigm for cardiac repair following AMI. This review discusses the potential use of biologically based ECM surrogates in the clinical setting following STEMI. PMID- 22090351 TI - Pharmacokinetics of oral ibuprofen for patent ductus arteriosus closure in preterm infants. PMID- 22090350 TI - The "missing" link between acute hemodynamic effect and clinical response. AB - The hemodynamic, mechanical and electrical effects of cardiac resynchronization therapy (CRT) occur immediate and are lasting as long as CRT is delivered. Therefore, it is reasonable to assume that acute hemodynamic effects should predict long-term outcome. However, in the literature there is more evidence against than in favour of this idea. This raises the question of what factor(s) do relate to the benefit of CRT. There is increasing evidence that dyssynchrony, presumably through the resultant abnormal local mechanical behaviour, induces extensive remodelling, comprising structure, as well as electrophysiological and contractile processes. Resynchronization has been shown to reverse these processes, even in cases of limited hemodynamic improvement. These data may indicate the need for a paradigm shift in order to achieve maximal long-term CRT response. PMID- 22090352 TI - [Long-term care of Parkinson patients with deep brain stimulation]. AB - For more than 15 years deep brain stimulation of the subthalamic nucleus and globus pallidus internus have become therapeutic options in advanced Parkinson's disease. The number of patients with long-term treatment is increasing steadily. This review focuses on issues of the long-term care of these Parkinson's patients, including differences of the available deep brain stimulation systems, recommendations for follow-up examinations, implications for medical diagnostics and therapies and an algorithm for symptom deterioration. Today, there is no profound evidence that deep brain stimulation prevents disease progression. However, symptomatic relief from motor symptoms is maintained during long-term follow-up and interruption of the therapy remains an exception. PMID- 22090353 TI - [Functional magnetic stimulation as a supposedly 'painless' option for movement induction in plegics]. AB - BACKGROUND: It is known in the rehabilitation of central pareses that functional electrical stimulation (FES) of the muscles can induce movement and accomplish training in patients. The main limitations of this method are that patients with preserved sensation experience pain and the reflexes triggered by FES. Therefore the application of the largely "painless" magnetic stimulation (FMS) of the muscles would be a potential alternative in the rehabilitation of patients with partially preserved sensation. As the generation of high force and power levels is considered to be an essential requirement of effective rehabilitation strategies, we have shown in previous work that FMS with large surface magnetic coils fitted to the thigh can generate about 2.5 times higher isometric forces in patients with preserved sensation, than can FES. OBJECTIVES: The goal of the present pilot study was to prove that the mechanical power generated by functional magnetic stimulation is superior to that produced by electrical stimulation too. METHODS: We have measured the mechanical torque, the power, the accomplished work and the kinematics in 4 healthy control subjects, who performed pedalling propelled by FMS and FES until complete muscular exhaustion, using a cycling test-bed under isotonic conditions (constant resistance). RESULTS: We have proved that the generated work, mean power, cadence and smoothness of pedalling essentially depend on peak torque and power. Furthermore, we found evidence that smoother pedalling could be achieved using magnetic, compared to electrical stimulation because of the higher peak torques that were generated by FMS. CONCLUSION: This study supports the concept that peripheral magnetic stimulation is an appropriate rehabilitation method for patients with central pareses and preserved sensory apparatus because FMS is less painful than electrical stimulation. PMID- 22090354 TI - Extremity soft tissue sarcoma resections: how wide do you need to be? AB - BACKGROUND: Sarcomas require a wide margin of resection including a cuff of normal tissue to minimize the risk of local recurrence. The amount of tissue that constitutes a wide margin is unclear in the literature. QUESTIONS/PURPOSES: We therefore determined whether a close resection margin for soft tissue sarcoma resulted in an increased incidence of locally recurrent disease and whether additional factors, including radiation therapy, outside biopsies, and tumor biology, affected the risk of local recurrence. METHODS: We retrospectively reviewed 117 patients with soft tissue sarcomas resected with negative margins from 2001 to 2007. Gross specimens were inked and the closest macroscopic margins were sent for microscopic examination. Resection margins were categorized as less than 1 mm, 1-5 mm, or greater than 5 mm. We evaluated additional factors that might influence local recurrence, including radiation therapy, outside biopsies, sarcoma type, grade, and stage at presentation, and development of metastatic disease. RESULTS: Four of 117 patients (3.4%) developed local recurrence. The incidence of local recurrence was similar in patients with less than 1-mm margins and greater than 1-mm margins: two of 45 patients (4.4%) and two of 64 patients (3.1%), respectively. Due to the low number of local recurrences, quantitative margin extent and the other factors evaluated did not affect local recurrence. CONCLUSIONS: The extent of a margin necessary to prevent local recurrence of soft tissue sarcoma remains unclear as the power of our study was limited by the low number of local recurrences. Relatively low local recurrence rates can be achieved even with close margins. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22090355 TI - Tantalum augments for Paprosky IIIA defects remain stable at midterm followup. AB - BACKGROUND: Initial reports with short-term followup of porous tantalum acetabular components and augments for Paprosky IIIA acetabular defects demonstrate high hip scores, low rates of aseptic loosening, and low rates of complications. However, longer-term followup with a larger cohort is needed to determine the durability of these reconstructions. QUESTIONS/PURPOSES: We therefore determined the functional scores, rates of aseptic loosening, and complications in patients with Paprosky IIIA acetabular defects treated with porous tantalum acetabular components and augments. METHODS: We retrospectively reviewed 37 acetabular revisions in 36 patients (one patient with bilateral revisions) treated with a porous tantalum acetabular component and augment. All patients had defects classified as Type IIIa using the system of Paprosky et al. Harris hip scores were obtained and radiographic examination was performed before surgery and through most recent followup. The minimum followup was 26 months (mean, 60 months; range, 26-106 months). RESULTS: One patient developed aseptic loosening of the acetabular reconstruction requiring revision; seven other patients required further surgery for periprosthetic femoral fracture (two), acute infection (three), and recurrent dislocation (two). Thirty-five of 37 hips had no or occasional pain at final followup. Mean Harris hip scores improved from 33.0 preoperatively (range, 12.6-58.7) to 81.5 postoperatively (range, 27.0 99.8). CONCLUSIONS: Although the complication rate requiring further surgery was considerable, most patients with these reconstructions had pain relief and reasonable function with low rates of loosening at midterm followup. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22090356 TI - The natural history of idiopathic frozen shoulder: a 2- to 27-year followup study. AB - BACKGROUND: The natural history of spontaneous idiopathic frozen shoulder is controversial. Many studies claim that complete resolution is not inevitable. Based on the 40-year clinical experience of the senior author, we believed most patients with idiopathic frozen shoulder might have a higher rate of resolution than earlier thought. QUESTIONS/PURPOSES: We determined the length of symptoms, whether spontaneous frozen shoulder recovered without any treatment, and whether restored ROM, pain relief, and function persisted over the long term. METHODS: We retrospectively reviewed 83 patients treated for frozen shoulder (84 shoulders; 56 women) 2 to 27 years (mean, 9 years) after initial consultation. The mean age at onset of symptoms was 53 years. Fifty-one of the 83 patients (52 shoulders) were treated with observation or benign neglect only (untreated group), and 32 had received some kind of nonoperative treatment before the first consultation with the senior author (nonoperative group). We also evaluated all 20 patients (22 shoulders; 13 women) with spontaneous frozen shoulder who underwent manipulation under anesthesia during the same time (manipulation group). The mean age of these patients was 49 years. The minimum followup was 2 years (mean, 14 years; range, 2-24 years). We determined duration of the disease, pain levels, ROM, and Constant-Murley scores. RESULTS: The duration of the disease averaged 15 months (range, 4-36 months) in the untreated group, and 20 months (range, 6-60 months) in the nonoperative group. At last followup the ROM had improved to the contralateral level in 94% in the untreated group, in 91% in the nonoperative group, and in 91% in the manipulation group. Fifty-one percent of patients in the untreated group, 44% in the nonoperative group, and 30% in the manipulation group were totally pain free at rest, during the night, and with exertion. Pain at rest was less than 3 on the VAS in 94% of patients in the untreated group, 91% in the nonoperative group, and 90% of the manipulation group. The Constant-Murley scores averaged 83 (86%) in the untreated group, 81 (77%) in the nonoperative group, and 82 (71%) in the manipulation group, reaching the normal age- and gender-related Constant-Murley score. CONCLUSIONS: We found 94% of patients with spontaneous frozen shoulder recovered to normal levels of function and motion without treatment. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22090357 TI - Environmental tobacco and wood smoke increase the risk of Legg-Calve-Perthes disease. AB - BACKGROUND: The etiology of Legg-Calve-Perthes disease (LCPD) remains unknown. A few studies have suggested passive smoke inhalation may be a risk factor, although the association is not confirmed and a causal relationship has not been established. QUESTIONS/PURPOSES: We therefore undertook this study to confirm an association between environmental tobacco smoke, firewood smoke, and socioeconomic status and the risk of LCPD. METHODS: We prospectively recruited 128 children with LCPD and 384 children attending the hospital for other orthopaedic complaints. The control subjects were frequency-matched with the cases by age and gender. Conditional logistic regression was used to assess the association between the exposures and risk of LCPD. RESULTS: The main risk factors for LCPD were indoor use of a wood stove (adjusted odds ratio [OR], 2.56) and having a family member who smoked indoors (adjusted OR, 2.07). Children from the middle socioeconomic group appeared to be at a greater risk of developing LCPD (adjusted OR, 3.60). CONCLUSIONS: This study provides further evidence that environmental tobacco smoke is associated with an increased risk of LCPD. Exposure to wood smoke also appears to be a risk factor. However, it remains unclear why there are profound differences in the incidence of the disease between regions when the prevalence of smoking is comparable and why bilateral involvement and familial disease are infrequent. PMID- 22090358 TI - Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. AB - PURPOSE: Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. EXPERIMENTAL DESIGN: Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. RESULTS: Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. CONCLUSION: Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. PMID- 22090359 TI - STAT5A-mediated SOCS2 expression regulates Jak2 and STAT3 activity following c Src inhibition in head and neck squamous carcinoma. AB - PURPOSE: The inhibition of c-Src results in a striking reduction in cancer cell invasion, but the effect on cell survival is modest. Defining mechanisms that limit apoptosis following c-Src inhibition could result in an ideal therapeutic approach that both inhibits invasion and leads to apoptosis. In this regard, we discovered a novel feedback loop that results in STAT3 reactivation following sustained c-Src inhibition. Here we define the mechanism underlying this feedback loop and examine the effect of inhibiting it in vivo. EXPERIMENTAL DESIGN: We measured levels and activity of pathway components using PCR, Western blotting, and kinase assays following their manipulation using both molecular and pharmacologic approaches. We used a heterotransplant animal model in which human oral squamous cancer is maintained exclusively in vivo. RESULTS: Following c-Src inhibition, STAT5 is durably inhibited. The inhibition of STAT5A, but not STAT5B, subsequently reduces the expression of suppressors of cytokine signaling 2 (SOCS2). SOCS2 inhibits Janus kinase 2 (Jak2) activity and Jak2-STAT3 binding. SOCS2 expression is necessary for STAT3 inhibition by c-Src inhibitors. Overexpression of SOCS2 is adequate to prevent STAT3 reactivation and to enhance the cytotoxic effects of c-Src inhibition. Likewise, the combination of Jak and c Src inhibitors led to significantly more apoptosis than either agent alone in vivo. CONCLUSIONS: To our knowledge, ours is the first study that fully defines the mechanism underlying this feedback loop, in which sustained c-Src inhibition leads to diminished SOCS2 expression via sustained inhibition of STAT5A, allowing activation of Jak2 and STAT3, Jak2-STAT3 binding, and survival signals. PMID- 22090360 TI - TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation-induced senescence. AB - PURPOSE: Mortality of patients with head and neck squamous cell carcinoma (HNSCC) is primarily driven by tumor cell radioresistance leading to locoregional recurrence (LRR). In this study, we use a classification of TP53 mutation (disruptive vs. nondisruptive) and examine impact on clinical outcomes and radiation sensitivity. EXPERIMENTAL DESIGN: Seventy-four patients with HNSCC treated with surgery and postoperative radiation and 38 HNSCC cell lines were assembled; for each, TP53 was sequenced and the in vitro radioresistance measured using clonogenic assays. p53 protein expression was inhibited using short hairpin RNA (shRNA) and overexpressed using a retrovirus. Radiation-induced apoptosis, mitotic cell death, senescence, and reactive oxygen species (ROS) assays were carried out. The effect of the drug metformin on overcoming mutant p53-associated radiation resistance was examined in vitro as well as in vivo, using an orthotopic xenograft model. RESULTS: Mutant TP53 alone was not predictive of LRR; however, disruptive TP53 mutation strongly predicted LRR (P = 0.03). Cell lines with disruptive mutations were significantly more radioresistant (P < 0.05). Expression of disruptive TP53 mutations significantly decreased radiation-induced senescence, as measured by SA-beta-gal staining, p21 expression, and release of ROS. The mitochondrial agent metformin potentiated the effects of radiation in the presence of a disruptive TP53 mutation partially via senescence. Examination of our patient cohort showed that LRR was decreased in patients taking metformin. CONCLUSIONS: Disruptive TP53 mutations in HNSCC tumors predicts for LRR, because of increased radioresistance via the inhibition of senescence. Metformin can serve as a radiosensitizer for HNSCC with disruptive TP53, presaging the possibility of personalizing HNSCC treatment. PMID- 22090361 TI - Anti-EGFR antibody cetuximab enhances the cytolytic activity of natural killer cells toward osteosarcoma. AB - PURPOSE: Osteosarcoma and Ewing's sarcoma are the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease have a poor prognosis, illustrating the need for alternative therapies. Sarcoma cells are susceptible to the cytolytic activity of resting natural killer (NK) cells which can be improved by interleukin (IL)-15 stimulation. In this study, we explored whether the cytolytic function of resting NK cells can be augmented and specifically directed toward sarcoma cells by antibody-dependent cellular cytotoxicity (ADCC). EXPERIMENTAL DESIGN: Epidermal growth factor receptor (EGFR) expression was examined on osteosarcoma and Ewing's sarcoma cell lines by flow cytometry and in osteosarcoma biopsy and resection specimens by immunohistochemistry. Cetuximab-mediated ADCC by NK cells from osteosarcoma patients and healthy controls was measured with 4-hour (51)Cr release assays. RESULTS: EGFR surface expression was shown on chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cells (12/12), most primary osteosarcoma cultures (4/5), and few Ewing's sarcoma cell lines (2/7). In the presence of cetuximab, the cytolytic activity of resting NK cells against all EGFR-expressing sarcoma cells was substantially increased and comparable with that of IL-15 activated NK cells. Surface EGFR expression on primary osteosarcoma cultures correlated with EGFR expression in the original tumor. The cytolytic activity of osteosarcoma patient-derived NK cells against autologous tumor cells was as efficient as that of NK cells from healthy donors. CONCLUSION: Our data show that the cytolytic potential of resting NK cells can be potentiated and directed toward osteosarcoma cells with cetuximab. Therefore, cetuximab-mediated immunotherapy may be considered a novel treatment modality in the management of advanced osteosarcoma. PMID- 22090362 TI - Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer. AB - PURPOSE: To identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the first-in-class, oral CDK4/6 inhibitor PD 0332991 administered once daily for 21 of 28 days (3/1 schedule) in patients with retinoblastoma protein (Rb)-positive advanced solid tumors and to describe pharmacokinetic pharmacodynamic relationships relative to drug effects. EXPERIMENTAL DESIGN: This open-label phase I study (NCT00141297) enrolled patients who received PD 0332991 orally in six dose-escalation cohorts in a standard 3 + 3 design. RESULTS: Forty one patients were enrolled. DLTs were observed in five patients (12%) overall; at the 75, 125, and 150 mg once daily dose levels. The MTD and recommended phase II dose of PD 0332991 was 125 mg once daily. Neutropenia was the only dose-limiting effect. After cycle 1, grade 3 neutropenia, anemia, and leukopenia occurred in five (12%), three (7%), and one (2%) patient(s), respectively. The most common non-hematologic adverse events included fatigue, nausea, and diarrhea. Thirty seven patients were evaluable for tumor response; 10 (27%) had stable disease for >=4 cycles of whom six derived prolonged benefit (>=10 cycles). PD 0332991 was slowly absorbed (median T(max), 5.5 hours), and slowly eliminated (mean half-life was 25.9 hours) with a large volume of distribution (mean, 2,793 L). The area under the concentration-time curve increased linearly with dose. Using an E(max) model, neutropenia was shown to be proportional to exposure. CONCLUSIONS: PD 0332991 warrants phase II testing at 125 mg once daily, at which dose neutropenia was the sole significant toxicity. PMID- 22090363 TI - An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease. AB - The aims were to determine the effect of an oral inhibitor of the signaling mediator p38 mitogen-activated protein kinase (GW856553, losmapimod) on sputum neutrophils, pulmonary function, and blood biomarkers of inflammation in chronic obstructive pulmonary disease (COPD). Three hundred and two individuals with GOLD stage II COPD were randomized to oral losmapimod 7.5 mg twice daily, inhaled salmeterol/fluticasone propionate 50 ug/500 ug combination (SFC), or placebo in a 12-week, randomized, double-blind, double-dummy study (MKI102428/NCT00642148). Neither losmapimod nor SFC had an effect on the primary end point of sputum neutrophils. Losmapimod was well tolerated and reduced plasma fibrinogen by 11% ( 0.4 g/L, ratio of effect of losmapimod/placebo 0.89; 95% confidence interval, 0.83-0.96; P = .002) with nonsignificant reductions in interleukin-6, interleukin 8, and C-reactive protein. There was evidence of improvement in hyperinflation with losmapimod compared with placebo (overall P = .02). Inhaled SFC significantly improved lung function and reduced serum CC-16 (ratio of effect of SFC/placebo 0.87; 95% confidence interval, 0.82-0.93; P < .001). It was concluded that oral losmapimod significantly reduced plasma fibrinogen in patients with COPD. PMID- 22090364 TI - Specification and differentiation of cerebellar GABAergic neurons. AB - Cerebellar GABAergic projection neurons and interneurons originate from the ventricular neuroepithelium of the cerebellar primordium. However, while projection neurons are born within this germinal layer, interneurons derive from progenitors that delaminate into the prospective white matter. In spite of this common origin, the two main classes of GABAergic neurons are generated according to distinct strategies. Projection neurons are committed to their fate at early ontogenetic stages and acquire their mature phenotypes through cell-autonomous mechanisms. On the contrary, the different categories of cerebellar interneurons derive from a single pool of multipotent progenitors, whose fate choices, production rates and differentiation schedules are strongly influenced by environmental cues. PMID- 22090365 TI - Regulation of inhibitory synaptic plasticity in a Purkinje neuron. AB - Inhibitory synapses on Purkinje cells show synaptic plasticity such as rebound potentiation (RP), which seems to contribute to refined information processing in the cerebellar cortex. Recent progress in the study on regulation mechanism of RP is reported. RP is induced by depolarization of a Purkinje cell and expressed as the increased postsynaptic responsiveness to GABA. RP might work as a homeostatic mechanism to maintain activity of a Purkinje cell sensing the strength of heterosynaptic excitatory inputs. However, there is a homosynaptic mechanism to regulate RP. RP is suppressed by the GABAergic transmission occurring during depolarization. Elaborate molecular regulation mechanism of RP induction, including GABA(B) receptors, Ca(2+), cyclic adenosine 3',5'-monophosphate (cAMP), kinases such as Ca(2+)- and calmodulin-dependent kinase II and protein kinase A, and protein phosphatases such as PP1 and PP2B, has been clarified. Application of systems biological analyses combined with electrophysiological experiments has revealed a critical role of phosphodiesterase 1 in determination of the Ca(2+) signal to induce RP. PMID- 22090366 TI - Body mass index is inversely correlated with the expanded CAG repeat length in SCA3/MJD patients. AB - Spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), is an autosomal dominant neurodegenerative disorder with no current treatment. We aimed to evaluate the body mass index (BMI) of patients with SCA3/MJD and to assess the correlations with clinical, molecular, biochemical, and neuroimaging findings. A case-control study with 46 SCA3/MJD patients and 42 healthy, non related control individuals with similar age and sex was performed. Clinical evaluation was done with the ataxia scales SARA and NESSCA. Serum insulin, insulin-like growth factor 1 (IGF-1) and magnetic resonance imaging normalized volumetries of cerebellum and brain stem were also assessed. BMI was lower in SCA3/MJD patients when compared to controls (p = 0.01). BMI was associated with NESSCA, expanded CAG repeat number (CAG)n, age of onset, age, disease duration, and serum insulin levels; however, in the linear regression model, (CAG)n was the only variable independently associated with BMI, in an inverse manner (R = 0.396, p = 0.015). In this report, we present evidence that low BMI is not only present in SCA3/MJD, but is also directly related to the length of the expanded CAG repeats, which is the causative mutation of the disease. This association points that weight loss might be a primary disturbance of SCA3/MJD, although further detailed analyses are necessary for a better understanding of the nutritional deficit and its role in the pathophysiology of SCA3/MJD. PMID- 22090368 TI - ["Can They Still be Helped?" - Psychosocial and Emergency Management in the Public Helath Service. Position paper of the Germany Society of Physicians in the Public Health Service]. PMID- 22090369 TI - [The legal basis for the work of the sociopsychiatric services in Germany]. AB - INTRODUCTION: The legal basic principles of community mental health services or sociopsychiatric services (SpDi) in the Federal Republic of Germany are state, not federal laws, namely laws on help and protective measures for mentally disordered people (PsychKG) and laws on Public Health Services (OGDG) as SpDi are all integral parts of Community Public Health Authorities in most places. State laws of the 16 German states differ considerably. Earlier research on PsychKG focussed exclusively on involuntary hospitalisation, this work is the first to address PsychKG as related to the work of SpDi and to consider OGDG as well. METHODS: Based on an internet-based literature review the expedient laws of the 16 German states were systematically reviewed and compared. RESULTS: There is an OGDG in 15/16 states, a PsychKG in 12/16 and some laws concerning SpDi in 13/16. Where OGDG has health support to socially disadvantaged people, there is also a law on SpDi. SpDi are mainly part of the municipal or county health authorities except for 3 states without PsychKG. Where there is a legal basis, SpDi fulfills the 5 core tasks of counselling and support, crisis intervention, psychiatric expertise, coordination of mental health services and controlling of mental health institutions. CONCLUSION: In every day practice, the "Recommendations of the Board of Experts" of 1988 are more relevant than the actual state laws. However, where no such law has been passed, the impact of the "Recommendations" was much weaker. As PsychKG and OGDG do not warrant individual claims, but give only general indications of action, precise standards of practice are needed, as they were recently formulated in the state of Schleswig-Holstein. The UN Convention on the rights of disabled persons with its claim to more assistance may be facilitating the process of further development of state laws and to the work of the community mental health services based on them. PMID- 22090370 TI - [Variety of live worlds - relationship between living situation and developmental status in school beginners]. AB - What is most important if we want to support children in the community of Recklinghausen, which is one of the most populous rural districts in Germany? With this interest in mind, data from health check assessments which are regularly done at primary school enrolment were analysed. For analysis the recommended "Bielefelder Modell" was used. The sample included all children who entered primary school in the region of Recklinghausen in 2006-2009 (n=23 600). These data allowed us to link information about their physical condition and cognitive development with issues of social background, environment as well as to search for regional patterns. We found a broad variety of "live worlds" of children in our community, most striking were substantial inequalities regarding utilisation of screening examinations as well as education and training opportunities. A strong link to parents' educational and immigrant background was evident. The procedure for analysing these data with a focus on regional patterns provides a valuable insight into local inequalities. It provides a knowledge base for a policy of early interventions to provide all children with the same opportunities for good health and development. PMID- 22090371 TI - [Medical and Economic Aspects of Extracorporeal Shock Wave Lithotripsy]. AB - Extracorporeal shock wave lithotripsy (ESWL) is the method of choice for most renal and ureteral calculi. However, endoscopic procedures such as ureteroscopy or percutaneous nephrolithotomy are being more and more performed as primary treatment alternatives in clinical routine. This development may result from the sometimes unsatisfying results of ESWL. While this is often explained by a lower efficacy of last-generation machines, an often unrecognized explanation is the impact of a less well trained urologist. To achieve best results it is mandatory that fundamental knowledge about shock wave physics and disintegration mechanisms are available. In Germany, the reimbursement system between outpatient and inpatient departments is totally separate. This leads to difficulties in clinical practice. We believe that patients at risk for complications, such as ureteral stones, urinary tract infections or high age, benefit from inpatient treatment, while uncomplicated renal stones can safely be treated on an outpatient basis. Regular application and training of ESWL will aid an optimization of its results and acceptance. PMID- 22090372 TI - [Stool behaviour and local pain after radical perineal and retroperitoneal prostatectomy]. AB - PURPOSE: One of the main therapeutic targets of a radical prostatectomy (RP) as a treatment for -localised prostate cancer is the maintenance of quality of life after surgery besides the known oncological and functional effects. This prospective study compared the quality of life after surgery of patients treated with two different surgical methods (perineal RP, RPP; retropubic RP, RRP). The aim of this study was to compare perineal and retropubic RP with regard to stool behaviour and local pain symptoms. PATIENTS AND METHODS: 257 radical prostatectomies (169 RPP, 88 RRP) were performed between July 2003 and December 2004. 208 (151 RPP, 57 RRP) prospectively evaluated patients replied to a physician-independent validated questionnaire (QLQ-C30 with prostate modul, IIEF 75, stool behaviour) followed by a phone survey regarding the continence of all 257 patients. RESULTS: One year after surgery, the complete continence rate (no pads) was 75 % for the RPP group and 61 % for the RRP group. 22 % of the patients reported involuntary stool leakage in the RPP group and 19 % in the RRP group (not significantly different). 29 % of the patients in the RPP group complained of local pain after 12 months, one third of them while sitting. In the RRP group, 28 % of the patients complained of local pain after 12 months, 15 % of them while sitting.17 % in the RPP and 27 % in the RRP group who suffered of stool leakage had these symptoms preoperatively. One year after surgery, 52 % of preoperatively potent patients were still potent after nerve-sparing RPP and 40 % were potent after nerve-sparing RRP. 78 % of patients in the RPP group and 67 % in the RRP group had an overall satisfactory quality of life. CONCLUSION: The application of different surgical methods did not differ with regard to postoperative local pain, stool behaviour, or general health items of quality of life. Stool leakage and perineal pain while sitting were not limited to RPP only and about a quarter of these patients had suffered from stool leakage already be fore surgery. PMID- 22090373 TI - [Partial and total penectomy]. PMID- 22090374 TI - Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells. AB - Cell-type diversity is governed in part by differential gene expression programs mediated by transcription factor (TF) binding. However, there are few systematic studies of the genomic binding of different types of TFs across a wide range of human cell types, especially in relation to gene expression. In the ENCODE Project, we have identified the genomic binding locations across 11 different human cell types of CTCF, RNA Pol II (RNAPII), and MYC, three TFs with diverse roles. Our data and analysis revealed how these factors bind in relation to genomic features and shape gene expression and cell-type specificity. CTCF bound predominantly in intergenic regions while RNAPII and MYC preferentially bound to core promoter regions. CTCF sites were relatively invariant across diverse cell types, while MYC showed the greatest cell-type specificity. MYC and RNAPII co localized at many of their binding sites and putative target genes. Cell-type specific binding sites, in particular for MYC and RNAPII, were associated with cell-type specific functions. Patterns of binding in relation to gene features were generally conserved across different cell types. RNAPII occupancy was higher over exons than adjacent introns, likely reflecting a link between transcriptional elongation and splicing. TF binding was positively correlated with the expression levels of their putative target genes, but combinatorial binding, in particular of MYC and RNAPII, was even more strongly associated with higher gene expression. These data illuminate how combinatorial binding of transcription factors in diverse cell types is associated with gene expression and cell-type specific biology. PMID- 22090375 TI - Developmental control of gene copy number by repression of replication initiation and fork progression. AB - Precise DNA replication is crucial for genome maintenance, yet this process has been inherently difficult to study on a genome-wide level in untransformed differentiated metazoan cells. To determine how metazoan DNA replication can be repressed, we examined regions selectively under-replicated in Drosophila polytene salivary glands, and found they are transcriptionally silent and enriched for the repressive H3K27me3 mark. In the first genome-wide analysis of binding of the origin recognition complex (ORC) in a differentiated metazoan tissue, we find that ORC binding is dramatically reduced within these large domains, suggesting reduced initiation as one mechanism leading to under replication. Inhibition of replication fork progression by the chromatin protein SUUR is an additional repression mechanism to reduce copy number. Although repressive histone marks are removed when SUUR is mutated and copy number restored, neither transcription nor ORC binding is reinstated. Tethering of the SUUR protein to a specific site is insufficient to block replication, however. These results establish that developmental control of DNA replication, at both the initiation and elongation stages, is a mechanism to change gene copy number during differentiation. PMID- 22090376 TI - Aberrant firing of replication origins potentially explains intragenic nonrecurrent rearrangements within genes, including the human DMD gene. AB - Non-allelic homologous recombination (NAHR), non-homologous end joining (NHEJ), and microhomology-mediated replication-dependent recombination (MMRDR) have all been put forward as mechanisms to explain DNA rearrangements associated with genomic disorders. However, many nonrecurrent rearrangements in humans remain unexplained. To further investigate the mutation mechanisms of these copy number variations (CNVs), we performed breakpoint mapping analysis for 62 clinical cases with intragenic deletions in the human DMD gene (50 cases) and other known disease-causing genes (one PCCB, one IVD, one DBT, three PAH, one STK11, one HEXB, three DBT, one HRPT1, and one EMD cases). While repetitive elements were found in only four individual cases, three involving DMD and one HEXB gene, microhomologies (2-10 bp) were observed at breakpoint junctions in 56% and insertions ranging from 1 to 48 bp were seen in 16 of the total 62 cases. Among these insertions, we observed evidence for tandem repetitions of short segments (5-20 bp) of reference sequence proximal to the breakpoints in six individual DMD cases (six repeats in one, four repeats in three, two repeats in one, and one repeat in one case), strongly indicating attempts by the replication machinery to surpass the stalled replication fork. We provide evidence of a novel template slippage event during replication rescue. With a deeper insight into the complex process of replication and its rescue during origin failure, brought forward by recent studies, we propose a hypothesis based on aberrant firing of replication origins to explain intragenic nonrecurrent rearrangements within genes, including the DMD gene. PMID- 22090377 TI - Interlocus gene conversion events introduce deleterious mutations into at least 1% of human genes associated with inherited disease. AB - Establishing the molecular basis of DNA mutations that cause inherited disease is of fundamental importance to understanding the origin, nature, and clinical sequelae of genetic disorders in humans. The majority of disease-associated mutations constitute single-base substitutions and short deletions and/or insertions resulting from DNA replication errors and the repair of damaged bases. However, pathological mutations can also be introduced by nonreciprocal recombination events between paralogous sequences, a phenomenon known as interlocus gene conversion (IGC). IGC events have thus far been linked to pathology in more than 20 human genes. However, the large number of duplicated gene sequences in the human genome implies that many more disease-associated mutations could originate via IGC. Here, we have used a genome-wide computational approach to identify disease-associated mutations derived from IGC events. Our approach revealed hundreds of known pathological mutations that could have been caused by IGC. Further, we identified several dozen high-confidence cases of inherited disease mutations resulting from IGC in ~1% of all genes analyzed. About half of the donor sequences associated with such mutations are functional paralogous genes, suggesting that epistatic interactions or differential expression patterns will determine the impact upon fitness of specific substitutions between duplicated genes. In addition, we identified thousands of hitherto undescribed and potentially deleterious mutations that could arise via IGC. Our findings reveal the extent of the impact of interlocus gene conversion upon the spectrum of human inherited disease. PMID- 22090378 TI - Preparation of high-quality next-generation sequencing libraries from picogram quantities of target DNA. AB - New sequencing technologies can address diverse biomedical questions but are limited by a minimum required DNA input of typically 1 MUg. We describe how sequencing libraries can be reproducibly created from 20 pg of input DNA using a modified transpososome-mediated fragmentation technique. Resulting libraries incorporate in-line bar-coding, which facilitates sample multiplexes that can be sequenced using Illumina platforms with the manufacturer's sequencing primer. We demonstrate this technique by providing deep coverage sequence of the Escherichia coli K-12 genome that shows equivalent target coverage to a 1-MUg input library prepared using standard Illumina methods. Reducing template quantity does, however, increase the proportion of duplicate reads and enriches coverage in low GC regions. This finding was confirmed with exhaustive resequencing of a mouse library constructed from 20 pg of gDNA input (about seven haploid genomes) resulting in ~0.4-fold statistical coverage of uniquely mapped fragments. This implies that a near-complete coverage of the mouse genome is obtainable with this approach using 20 genomes as input. Application of this new method now allows genomic studies from low mass samples and routine preparation of sequencing libraries from enrichment procedures. PMID- 22090379 TI - Calling amplified haplotypes in next generation tumor sequence data. AB - During tumor initiation and progression, cancer cells acquire a selective advantage, allowing them to outcompete their normal counterparts. Identification of the genetic changes that underlie these tumor acquired traits can provide deeper insights into the biology of tumorigenesis. Regions of copy number alterations and germline DNA variants are some of the elements subject to selection during tumor evolution. Integrated examination of inherited variation and somatic alterations holds the potential to reveal specific nucleotide alleles that a tumor "prefers" to have amplified. Next-generation sequencing of tumor and matched normal tissues provides a high-resolution platform to identify and analyze such somatic amplicons. Within an amplicon, examination of informative (e.g., heterozygous) sites deviating from a 1:1 ratio may suggest selection of that allele. A naive approach examines the reads for each heterozygous site in isolation; however, this ignores available valuable linkage information across sites. We, therefore, present a novel hidden Markov model-based method-Haplotype Amplification in Tumor Sequences (HATS)-that analyzes tumor and normal sequence data, along with training data for phasing purposes, to infer amplified alleles and haplotypes in regions of copy number gain. Our method is designed to handle rare variants and biases in read data. We assess the performance of HATS using simulated amplified regions generated from varying copy number and coverage levels, followed by amplicons in real data. We demonstrate that HATS infers the amplified alleles more accurately than does the naive approach, especially at low to intermediate coverage levels and in cases (including high coverage) possessing stromal contamination or allelic bias. PMID- 22090380 TI - Non-breeding feather concentrations of testosterone, corticosterone and cortisol are associated with subsequent survival in wild house sparrows. AB - Potential mechanistic mediators of Darwinian fitness, such as stress hormones or sex hormones, have been the focus of many studies. An inverse relationship between fitness and stress or sex hormone concentrations has been widely assumed, although empirical evidence is scarce. Feathers gradually accumulate hormones during their growth and provide a novel way to measure hormone concentrations integrated over time. Using liquid chromatography-tandem mass spectrometry, we measured testosterone, corticosterone and cortisol in the feathers of house sparrows (Passer domesticus) in a wild population which is the subject of a long term study. Although corticosterone is considered the dominant avian glucocorticoid, we unambiguously identified cortisol in feathers. In addition, we found that feathers grown during the post-nuptial moult in autumn contained testosterone, corticosterone and cortisol levels that were significantly higher in birds that subsequently died over the following winter than in birds that survived. Thus, feather steroids are candidate prospective biomarkers to predict the future survival of individuals in the wild. PMID- 22090381 TI - Evolution of spur-length diversity in Aquilegia petals is achieved solely through cell-shape anisotropy. AB - The role of petal spurs and specialized pollinator interactions has been studied since Darwin. Aquilegia petal spurs exhibit striking size and shape diversity, correlated with specialized pollinators ranging from bees to hawkmoths in a textbook example of adaptive radiation. Despite the evolutionary significance of spur length, remarkably little is known about Aquilegia spur morphogenesis and its evolution. Using experimental measurements, both at tissue and cellular levels, combined with numerical modelling, we have investigated the relative roles of cell divisions and cell shape in determining the morphology of the Aquilegia petal spur. Contrary to decades-old hypotheses implicating a discrete meristematic zone as the driver of spur growth, we find that Aquilegia petal spurs develop via anisotropic cell expansion. Furthermore, changes in cell anisotropy account for 99 per cent of the spur-length variation in the genus, suggesting that the true evolutionary innovation underlying the rapid radiation of Aquilegia was the mechanism of tuning cell shape. PMID- 22090382 TI - High dispersal ability inhibits speciation in a continental radiation of passerine birds. AB - Dispersal can stimulate speciation by facilitating geographical expansion across barriers or inhibit speciation by maintaining gene flow among populations. Therefore, the relationship between dispersal ability and speciation rates can be positive or negative. Furthermore, an 'intermediate dispersal' model that combines positive and negative effects predicts a unimodal relationship between dispersal and diversification. Because both dispersal ability and speciation rates are difficult to quantify, empirical evidence for the relationship between dispersal and diversification remains scarce. Using a surrogate for flight performance and a species-level DNA-based phylogeny of a large South American bird radiation (the Furnariidae), we found that lineages with higher dispersal ability experienced lower speciation rates. We propose that the degree of fragmentation or permeability of the geographical setting together with the intermediate dispersal model are crucial in reconciling previous, often contradictory findings regarding the relationship between dispersal and diversification. PMID- 22090383 TI - Human activity selectively impacts the ecosystem roles of parrotfishes on coral reefs. AB - Around the globe, coral reefs and other marine ecosystems are increasingly overfished. Conventionally, studies of fishing impacts have focused on the population size and dynamics of targeted stocks rather than the broader ecosystem wide effects of harvesting. Using parrotfishes as an example, we show how coral reef fish populations respond to escalating fishing pressure across the Indian and Pacific Oceans. Based on these fish abundance data, we infer the potential impact on four key functional roles performed by parrotfishes. Rates of bioerosion and coral predation are highly sensitive to human activity, whereas grazing and sediment removal are resilient to fishing. Our results offer new insights into the vulnerability and resilience of coral reefs to the ever-growing human footprint. The depletion of fishes causes differential decline of key ecosystem functions, radically changing the dynamics of coral reefs and setting the stage for future ecological surprises. PMID- 22090384 TI - Bumble-bee learning selects for both early and long flowering in food-deceptive plants. AB - Most rewardless orchids engage in generalized food-deception, exhibiting floral traits typical of rewarding species and exploiting the instinctive foraging of pollinators. Generalized food-deceptive (GFD) orchids compete poorly with rewarding species for pollinator services, which may be overcome by flowering early in the growing season when relatively more pollinators are naive and fewer competing plant species are flowering, and/or flowering for extended periods to enhance the chance of pollinator visits. We tested these hypotheses by manipulating flowering time and duration in a natural population of Calypso bulbosa and quantifying pollinator visitation based on pollen removal. Both early and long flowering increased bumble-bee visitation compared with late and brief flowering, respectively. To identify the cause of reduced visitation during late flowering, we tested whether negative experience with C. bulbosa (avoidance learning) and positive experience with a rewarding species, Arctostaphylos uva ursi, (associative learning) by captive bumble-bees could reduce C. bulbosa's competitiveness. Avoidance learning explained the higher visitation of early- compared with late-flowering C. bulbosa. The resulting pollinator-mediated selection for early flowering may commonly affect GFD orchids, explaining their tendency to flower earlier than rewarding orchids. For dissimilar deceptive and rewarding sympatric species, associative learning may additionally favour early flowering by GFD species. PMID- 22090385 TI - Microbial to reef scale interactions between the reef-building coral Montastraea annularis and benthic algae. AB - Competition between reef-building corals and benthic algae is of key importance for reef dynamics. These interactions occur on many spatial scales, ranging from chemical to regional. Using microprobes, 16S rDNA pyrosequencing and underwater surveys, we examined the interactions between the reef-building coral Montastraea annularis and four types of benthic algae. The macroalgae Dictyota bartayresiana and Halimeda opuntia, as well as a mixed consortium of turf algae, caused hypoxia on the adjacent coral tissue. Turf algae were also associated with major shifts in the bacterial communities at the interaction zones, including more pathogens and virulence genes. In contrast to turf algae, interactions with crustose coralline algae (CCA) and M. annularis did not appear to be antagonistic at any scale. These zones were not hypoxic, the microbes were not pathogen-like and the abundance of coral-CCA interactions was positively correlated with per cent coral cover. We propose a model in which fleshy algae (i.e. some species of turf and fleshy macroalgae) alter benthic competition dynamics by stimulating bacterial respiration and promoting invasion of virulent bacteria on corals. This gives fleshy algae a competitive advantage over corals when human activities, such as overfishing and eutrophication, remove controls on algal abundance. Together, these results demonstrate the intricate connections and mechanisms that structure coral reefs. PMID- 22090386 TI - Variation in annual and lifetime reproductive success of lance-tailed manakins: alpha experience mitigates effects of senescence on siring success. AB - The causes of variation in individual reproductive success over a lifetime are not well understood. In long-lived vertebrates, reproductive output usually increases during early adulthood, but it is difficult to disentangle the roles of development and learning on this gain of reproductive success. Lekking lance tailed manakins provide an opportunity to separate these processes, as the vast majority of male reproduction occurs after a bird obtains alpha status and maintains a display area in the lek, but the age at which males achieve alpha status varies widely. Using 11 years of longitudinal data on age, social status and genetic siring success, I assessed the factors influencing variation in siring success by individuals over their lifetimes. The data show increases in annual reproductive success with both age and alpha experience. At advanced ages, these gains were offset by senescence in fecundity. Individual ontogeny, rather than compositional change of the population, generated a nonlinear relationship of breeding tenure with lifetime success; age of assuming alpha status was unrelated to tenure as a breeder, or success in the alpha role. Importantly, these findings suggest that social experience can mitigate the negative effects of senescence in older breeders. PMID- 22090387 TI - Relevance of evolutionary history for food web structure. AB - Explaining the structure of ecosystems is one of the great challenges of ecology. Simple models for food web structure aim at disentangling the complexity of ecological interaction networks and detect the main forces that are responsible for their shape. Trophic interactions are influenced by species traits, which in turn are largely determined by evolutionary history. Closely related species are more likely to share similar traits, such as body size, feeding mode and habitat preference than distant ones. Here, we present a theoretical framework for analysing whether evolutionary history--represented by taxonomic classification- provides valuable information on food web structure. In doing so, we measure which taxonomic ranks better explain species interactions. Our analysis is based on partitioning of the species into taxonomic units. For each partition, we compute the likelihood that a probabilistic model for food web structure reproduces the data using this information. We find that taxonomic partitions produce significantly higher likelihoods than expected at random. Marginal likelihoods (Bayes factors) are used to perform model selection among taxonomic ranks. We show that food webs are best explained by the coarser taxonomic ranks (kingdom to class). Our methods provide a way to explicitly include evolutionary history in models for food web structure. PMID- 22090388 TI - Invasive rats and recent colonist birds partially compensate for the loss of endemic New Zealand pollinators. AB - Reported declines of pollinator populations around the world have led to increasing concerns about the consequences for pollination as a critical ecosystem function and service. Pollination could be maintained through compensation if remaining pollinators increase their contribution or if novel species are recruited as pollinators, but empirical evidence of this compensation is so far lacking. Using a natural experiment in New Zealand where endemic vertebrate pollinators still occur on one offshore island reserve despite their local extinction on the adjacent North Island, we investigated whether compensation could maintain pollination in the face of pollinator extinctions. We show that two recently arrived species in New Zealand, the invasive ship rat (Rattus rattus) and the recent colonist silvereye (Zosterops lateralis; a passerine bird), at least partly maintain pollination for three forest plant species in northern New Zealand, and without this compensation, these plants would be significantly more pollen-limited. This study provides empirical evidence that widespread non-native species can play an important role in maintaining ecosystem functions, a role that needs to be assessed when planning invasive species control or eradication programmes. PMID- 22090389 TI - An ecological approach to assessing the epidemiology of antimicrobial resistance in animal and human populations. AB - We examined long-term surveillance data on antimicrobial resistance (AMR) in Salmonella Typhimurium DT104 (DT104) isolates from concurrently sampled and sympatric human and animal populations in Scotland. Using novel ecological and epidemiological approaches to examine diversity, and phenotypic and temporal relatedness of the resistance profiles, we assessed the more probable source of resistance of these two populations. The ecological diversity of AMR phenotypes was significantly greater in human isolates than in animal isolates, at the resolution of both sample and population. Of 5200 isolates, there were 65 resistance phenotypes, 13 unique to animals, 30 unique to humans and 22 were common to both. Of these 22, 11 were identified first in the human isolates, whereas only five were identified first in the animal isolates. We conclude that, while ecologically connected, animals and humans have distinguishable DT104 communities, differing in prevalence, linkage and diversity. Furthermore, we infer that the sympatric animal population is unlikely to be the major source of resistance diversity for humans. This suggests that current policy emphasis on restricting antimicrobial use in domestic animals may be overly simplistic. While these conclusions pertain to DT104 in Scotland, this approach could be applied to AMR in other bacteria-host ecosystems. PMID- 22090390 TI - Infectious personalities: behavioural syndromes and disease risk in larval amphibians. AB - Behavioural consistency or predictability through time and/or different contexts ('syndromes' or 'personality types') is likely to have substantial influence on animal life histories and fitness. Consequently, there is much interest in the forces driving and maintaining various syndromes. Individual host behaviours have been associated with susceptibility to parasitism, yet the role of pre-existing personality types in acquiring infections has not been investigated experimentally. Using a larval amphibian-trematode parasite model system, we report that tadpoles generally showed consistency in their activity level in response to both novel food and parasite exposure. Not only were individual activity level and exploration in the novel food context correlated with each other and with anti-parasite behaviour, all three were significant predictors of host parasite load. This is the first empirical demonstration that host behaviours in other contexts are related to behaviours mitigating infection risk and, ultimately, host parasite load. We suggest that this system illustrates how reliably high levels of activity and exploratory behaviour in different contexts might maximize both energy acquisition and resistance to trematode parasites. Such benefits could drive selection for the behavioural syndrome seen here owing to the life histories and ecological circumstances typical of wood frog (Lithobates sylvaticus) larvae. PMID- 22090391 TI - Diversification of acorn worms (Hemichordata, Enteropneusta) revealed in the deep sea. AB - Enteropneusts (phylum Hemichordata), although studied extensively because of their close relationship to chordates, have long been considered shallow-water, burrowing animals. The present paper more than doubles the number of enteropneust species recorded in the deep sea based on high-resolution imaging and sampling with remotely operated vehicles. We provide direct evidence that some enteropneusts are highly mobile-using changes in posture and currents to drift between feeding sites-and are prominent members of deep, epibenthic communities. In addition, we provide ecological information for each species. We also show that despite their great morphological diversity, most deep-living enteropneusts form a single clade (the rediagnosed family Torquaratoridae) on the basis of rDNA sequences and morphology of the proboscis skeleton and stomochord. The phylogenetic position of the torquaratorids indicates that the group, after evolving from near-shore ancestors, radiated extensively in the deep sea. PMID- 22090392 TI - Electron microscopy redux. PMID- 22090393 TI - Composite mantle cell and diffuse large B-cell lymphoma: report of two cases. AB - Composite lymphomas are rare and involve the concurrent evolution of 2 distinct lymphoma types within a single organ or tissue. This study describes 2 cases of composite mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL), which has not previously been reported. Each case demonstrated distinct populations of CD20 positive small and large atypical B cells. In both cases, only the small lymphocytes were positive for CD5 and cyclin D1, and fluorescence in situ hybridization (FISH) showed a t(11;14) translocation in the small lymphocytes but not in the large cells. Molecular studies for B-cell clonality showed a possible clonal relationship between the 2 components in one case but not the other. This study describes in detail the morphology, immunophenotype, FISH, and molecular analysis of both components in each case. To the authors' knowledge, this represents the first report of juxtaposition of MCL with DLBCL that does not represent transformation of the mantle cell component. PMID- 22090394 TI - Structural analysis of a bacterial exo-alpha-D-N-acetylglucosaminidase in complex with an unusual disaccharide found in class III mucin. AB - CpGH89 is a family 89 glycoside hydrolase with exo-alpha-D-N acetylglucosaminidase activity that is produced by the human and animal pathogen Clostridium perfringens. This enzyme is active on the alpha-D-GlcpNAc-(1 -> 4)-D Galp motif that is displayed on the class III mucins within the gastric mucosa. Other members of this enzyme family, such as human NAGLU, are active on heparan. A truncated version of CpGH89 was rendered inactive through the mutation of two key catalytic residues, the protein crystallized and its structure determined in complex with alpha-D-GlcpNAc-(1 -> 4)-D-Galp to reveal the molecular details of how this unique disaccharide is recognized by CpGH89. An analysis of this substrate complex not only provides insight into how this enzyme selects for its mucin-presented substrate but also advances our understanding of how its clinically relevant mammalian counterparts are specific for heparan. PMID- 22090395 TI - A randomized, double-blind, crossover comparison of MK-0929 and placebo in the treatment of adults with ADHD. AB - OBJECTIVE: Preclinical models, receptor localization, and genetic linkage data support the role of D4 receptors in the etiology of ADHD. This proof-of-concept study was designed to evaluate MK-0929, a selective D4 receptor antagonist as treatment for adult ADHD. METHOD: A randomized, double-blind, placebo-controlled, crossover study was conducted in adults with primary ADHD. The primary end point was changed from baseline in total score on the Adult ADHD Investigator Symptom Rating Scale following a 4-week treatment regimen. Additional measures included Clinical Global Impression-Severity Scale, Hospital Anxiety and Depression Scale, and Brown Attention Deficit Disorder Scale and D4 genotype analysis. RESULTS: No statistically significant treatment differences were found between MK-0929 and placebo in any of the primary or secondary assessments. CONCLUSION: Results from this study suggest that blockade of the D4 receptor alone is not efficacious in the treatment of adult ADHD. PMID- 22090396 TI - A review of neurofeedback treatment for pediatric ADHD. AB - OBJECTIVE: The aim of this paper was to review all randomized published trials and unpublished conference presentations on the neurofeedback (NF) treatment of pediatric ADHD, and their relevance, strengths, and limitations. METHOD: Via PsychInfo and Medline searches and contacts with NF researchers 14 studies were identified and reviewed. RESULTS: The majority were conducted from 1994 to 2010, with 5- to 15-year-olds, usually male and White with the combined type of ADHD. Most studies used theta/beta NF with a unipolar-electrode placement at Cz and demonstrated, where reported, an overall ADHD mean effect size of d = 0.69, a medium effect. Main study strengths, within some studies, include use of randomization, treatment control conditions, Diagnostic and Statistical Manual of Mental Disorders criteria, evidence-based assessment of ADHD, standard treatment outcome measures, multidomain assessment, and, for some studies, moderate sample size, some type of blind and the identification of medication as a concomitant treatment. Main study limitations (and directions for future research) include the lack of adequate blinding of participants, raters and NF trainers, a sham NF/blinded control treatment condition, posttreatment follow-up, generalizability, specific details about delivery of NF, identification and control of comorbidity, and the identification, measurement, and control of concomitant treatments and potential side effects. CONCLUSION: Based on the results and methodologies of published studies, this review concludes that NF for pediatric ADHD can be currently considered as "probably efficacious." PMID- 22090398 TI - Involvement of methicillin-susceptible Staphylococcus aureus related to sequence type 25 and harboring pvl genes in a case of carotid cavernous fistula after community-associated sepsis. AB - Staphylococcus aureus encoding Panton-Valentine leukocidin (PVL) genes has become the cause of life-threatening infections. We describe a case of carotid cavernous fistula after bacteremia in a 12-year-old male, caused by a methicillin susceptible S. aureus isolate carrying the pvl, fnbA, and ebpS genes and related to sequence type 25 (ST25). The patient's condition was complicated by pleural empyema and osteomyelitis in the right femur. The patient was discharged in good clinical condition after 160 days of hospitalization. PMID- 22090399 TI - Relapse of Serratia marcescens sternal osteitis 15 years after the first episode. AB - Sternal osteitis, a potential consequence of cardiac surgery, remains rare. The bacteria involved belong mostly to the genus Staphylococcus. Sternal infections caused by Serratia marcescens are exceptional. We report an unusual recurrence of sternal infection with S. marcescens, 15 years after the initial episode. The identities of the isolates were determined by genomic analysis. PMID- 22090400 TI - Yield of sputum for viral detection by reverse transcriptase PCR in adults hospitalized with respiratory illness. AB - Diagnostic tests for respiratory viral infections have traditionally been performed on nasopharyngeal swabs or washings. Reverse transcriptase PCR (RT-PCR) is rapid, sensitive, and specific for viral infection diagnosis but is rarely applied to sputum samples. Thus, we evaluated the diagnostic yield of RT-PCR for detection of nine virus types by the use of nose and throat swabs (NTS) and sputum samples from patients admitted to the hospital with acute respiratory tract illnesses. Adults hospitalized with acute respiratory tract illnesses were recruited during the winters of 2008 and 2009. At enrollment, combined nose and throat swabs and sputum samples were collected for RT-PCR for detection of nine common respiratory virus types. A total of 532 subjects admitted for 556 respiratory illnesses were enrolled. A total of 189 virus strains were identified. The diagnostic yields for detection of any virus were 23% (126/556) for NTS RT-PCR and 36% (146/404) for sputum RT-PCR. A total of 83 (44%) of 189 viral detections were positive by both methods, 43 (23%) were positive by NTS alone, and 63 (33%) were positive only with sputum samples. The inclusion of RT PCR performed with sputum samples significantly increased the diagnostic yield for respiratory viral infections in adults. Further studies designed to adapt the use of sputum samples for commercial RT-PCR respiratory virus assays are needed. PMID- 22090401 TI - Direct maldi-tof mass spectrometry assay of blood culture broths for rapid identification of Candida species causing bloodstream infections: an observational study in two large microbiology laboratories. AB - We evaluated the reliability of the Bruker Daltonik's MALDI Biotyper system in species-level identification of yeasts directly from blood culture bottles. Identification results were concordant with those of the conventional culture based method for 95.9% of Candida albicans (187/195) and 86.5% of non-albicans Candida species (128/148). Results were available in 30 min (median), suggesting that this approach is a reliable, time-saving tool for routine identification of Candida species causing bloodstream infection. PMID- 22090402 TI - Prevalence and sequence variation of panton-valentine leukocidin in methicillin resistant and methicillin-susceptible staphylococcus aureus strains in the United States. AB - Panton-Valentine leukocidin (PVL), encoded by the lukSF-PV genes, is a putative virulence factor and marker for community-associated methicillin-resistant Staphylococcus aureus. Here we report the prevalence of PVL among a representative sample of 1,055 S. aureus infection isolates from the United States and describe the sequence variation of the lukSF-PV genes. We performed multilocus sequence typing (MLST) on all isolates and sequenced fragments of the lukSF-PV genes from a sample of 86 isolates. We assigned isolates to a PVL R or H sequence type based on a polymorphism that results in an amino acid change from arginine (R) to histidine (H). Overall, we found that 36% of S. aureus isolates were positive for lukSF-PV. Among the 86 we typed, we identified 72 R variants and 14 H variants. Among the 47 methicillin-resistance S. aureus (MRSA) isolates, 43 harbored the R variant, and among the 39 methicillin-susceptible S. aureus (MSSA) isolates, 29 harbored the R variant. Almost all (97%) of the R variants were found in MLST clonal complex 8 (CC8), while the H variant was broadly distributed among 6 CCs. Within CC8, all 38 MRSA (USA300) and all 28 MSSA isolates harbored the R variant. Of the 20 isolates from blood and the lower respiratory tract, 19 (95%) harbored the R variant. While the R variant had been linked primarily to USA300 MRSA, we found that all CC8 MSSA isolates also contained the R variant, suggesting that some strains of USA300 may have lost methicillin resistance as an adaptation in the community. PMID- 22090403 TI - Comparison of the hybrid capture 2 and cobas 4800 tests for detection of high risk human papillomavirus in specimens collected in PreservCyt medium. AB - Clinical cervical cytology specimens (n = 466) collected in PreservCyt (Hologic Inc.) were used to evaluate the agreement between Hybrid Capture 2 (hc2; Qiagen) and cobas 4800 (c4800; Roche Molecular Diagnostics) for the detection of high risk human papillomavirus (HR HPV) genotype infections. The agreement between the two assays was 93.8% (kappa = 0.87; 95% confidence interval, 0.828 to 0.918), with 186 and 251 concordant positive and negative results, respectively. All 186 concordant positives were confirmed using the Linear Array (LA; Roche Molecular Diagnostics) genotyping test. Of the 29 samples with discordant results (6.2%), 18 were hc2 positive and LA verified 17 as positive for HR HPV. Eleven discordant specimens were c4800 positive, and LA confirmed 5 as positive for HR HPV. As of October 2009, practice guidelines in Alberta, Canada, recommend reflex HPV testing for women over 30 years old with atypical squamous cells of undetermined significance (ASCUS) and for women over 50 years old with low-grade squamous intraepithelial lesions (LSIL) to help prioritize those who should undergo further evaluation. In this study, agreement between hc2 and c4800 results for samples from women over 30 years old with ASCUS cytology was 92.3% (n = 13), while no samples from women over 50 years old with LSIL cytology were identified for analysis. PMID- 22090404 TI - Application of a microcalorimetric method for determining drug susceptibility in mycobacterium species. AB - Mycobacterium tuberculosis is a global public health concern, particularly with the emergence of drug-resistant strains. Immediate identification of drug resistant strains is crucial to administering appropriate treatment before the bacteria are allowed to spread. However, developing countries, which are most affected by drug resistance, are struggling to combat the disease without the facilities or funds for expensive diagnostics. Recent studies have emphasized the suitability of isothermal microcalorimetry (IMC) for the rapid detection of mycobacteria. In this study, we investigate its suitability for rapid and reliable M. tuberculosis drug susceptibility testing. Specifically, IMC was used to determine the MICs of three drugs, namely, isoniazid, ethambutol, and moxifloxacin, against three mycobacteria, namely, Mycobacterium smegmatis, Mycobacterium avium, and Mycobacterium tuberculosis. The Richards growth model was used to calculate growth parameters, namely, the maximum bacterial growth rate and the lag phase duration from integrated heat flow-versus-time results. For example, MICs of isoniazid, ethambutol, and moxifloxacin were determined to be 1.00, 8.00, and 0.25 MUg/ml, respectively. IMC, as described here, could be used not just in industrialized countries but also in developing countries because inexpensive and sensitive microcalorimeters are now available. PMID- 22090405 TI - It is time to use treponema-specific antibody screening tests for diagnosis of syphilis. AB - Assays that detect treponema-specific antibodies, which are either automated or can be done as point-of-care tests, have been developed, some of which are FDA approved. These assays have the advantage of being easily performed and demonstrate high sensitivity, both key features of an infectious disease screening test. As a result, many high-volume clinical laboratories have begun to offer a reverse syphilis testing algorithm where a treponema-specific test is used for screening, followed by a nontreponemal test (i.e., rapid plasma reagin [RPR]) to assess disease activity and treatment status. Concerns about physicians being able to understand and apply this new testing algorithm have been expressed (8). In this point-counterpoint, Michael Loeffelholz of the University of Texas Medical Branch at Galveston explains why his laboratory has adopted this reverse algorithmic approach. Matthew Binnicker of the Mayo Clinic, Rochester, MN, explains why the reverse algorithm may not be suitable for all clinical laboratories and every clinical situation. PMID- 22090407 TI - Direct comparison of the traditional and reverse syphilis screening algorithms in a population with a low prevalence of syphilis. AB - We describe the first direct comparison of the reverse and traditional syphilis screening algorithms in a population with a low prevalence of syphilis. Among 1,000 patients tested, the results for 6 patients were falsely reactive by reverse screening, compared to none by traditional testing. However, reverse screening identified 2 patients with possible latent syphilis that were not detected by rapid plasma reagin (RPR). PMID- 22090406 TI - Development of a multiplex PCR assay for detection and genogrouping of Neisseria meningitidis. AB - Neisseria meningitidis is a leading pathogen of epidemic bacterial meningitis and fulminant sepsis worldwide. Twelve different N. meningitidis serogroups have been identified to date based on antigenic differences in the capsular polysaccharide. However, more than 90% of human cases of N. meningitidis meningitis are the result of infection with just five serogroups, A, B, C, W135, and Y. Efficient methods of detection and genogrouping of N. meningitidis isolates are needed, therefore, in order to monitor prevalent serogroups as a means of disease control and prevention. The capsular gene complex regions have been sequenced from only seven out of the 12 serogroups. In this study, the capsular gene complexes of the remaining five serogroups were sequenced and analyzed. Primers were designed that were specific for N. meningitidis species and for the 12 individual serogroups, and a multiplex PCR assay using these specific primers was developed for N. meningitidis detection and genogrouping. The assay was tested using 15 reference strains covering all 12 serogroups, 143 clinical isolates, and 21 strains from closely related species or from species that cause meningitis. The assay could detect N. meningitidis serogroups and was shown to be specific, with a detection sensitivity of 1 ng of genomic DNA (equivalent to ~4 * 10(5) genomes) or 3 * 10(5) CFU/ml in noncultured mock cerebrospinal fluid (CSF) specimens. This study, therefore, describes for the first time the development of a molecular protocol for the detection of all N. meningitidis serogroups. This multiplex PCR-based assay may have use for the clinical diagnosis and epidemiological surveillance of N. meningitidis. PMID- 22090408 TI - Performance assessment of the CapitalBio mycobacterium identification array system for identification of mycobacteria. AB - The CapitalBio Mycobacterium identification microarray system is a rapid system for the detection of Mycobacterium tuberculosis. The performance of this system was assessed with 24 reference strains, 486 Mycobacterium tuberculosis clinical isolates, and 40 clinical samples and then compared to the "gold standard" of DNA sequencing. The CapitalBio Mycobacterium identification microarray system showed highly concordant identification results of 100% and 98.4% for Mycobacterium tuberculosis complex (MTC) and nontuberculous mycobacteria (NTM), respectively. The sensitivity and specificity of the CapitalBio Mycobacterium identification array for identification of Mycobacterium tuberculosis isolates were 99.6% and 100%, respectively, for direct detection and identification of clinical samples, and the overall sensitivity was 52.5%. It was 100% for sputum, 16.7% for pleural fluid, and 10% for bronchoalveolar lavage fluid, respectively. The total assay was completed in 6 h, including DNA extraction, PCR, and hybridization. The results of this study confirm the utility of this system for the rapid identification of mycobacteria and suggest that the CapitalBio Mycobacterium identification array is a molecular diagnostic technique with high sensitivity and specificity that has the capacity to quickly identify most mycobacteria. PMID- 22090409 TI - Validation of pncA gene sequencing in combination with the mycobacterial growth indicator tube method to test susceptibility of Mycobacterium tuberculosis to pyrazinamide. AB - Pyrazinamide is important in the treatment of tuberculosis. Unfortunately, the diagnosis of pyrazinamide resistance is hampered by technical difficulties. We hypothesized that mutation analysis combined with the mycobacterial growth indicator tube (MGIT) phenotypic method would be a good predictor of pyrazinamide resistance. We prospectively analyzed 1,650 M. tuberculosis isolates referred to our tuberculosis reference laboratory in 2008 and 2009. In our laboratory, the MGIT 960 system was used for pyrazinamide resistance screening. If a pyrazinamide resistant strain was detected, we performed a pncA gene mutation analysis. A second MGIT 960 susceptibility assay was performed afterwards to evaluate the accuracy of the pncA mutation analysis to detect true- or false-positive MGIT results. We observed pyrazinamide resistance in 69 samples using the first MGIT 960 analysis. In a second MGIT 960 analysis, 47 of the 69 samples proved susceptible (68% false positivity). Sensitivity of nonsynonymous pncA mutations for detecting resistant isolates was 73% (95% confidence interval [CI], 61% to 73%), and specificity was 100% (95% CI, 95% to 100%). A diagnostic algorithm incorporating phenotypic and molecular methods would have a 100% positive predictive value for detecting pyrazinamide-resistant isolates, indicating that such an algorithm, based on both methods, is a good predictor for pyrazinamide resistance in routine diagnostics. PMID- 22090410 TI - Comparison of microscopy and PCR for detection of intestinal parasites in Danish patients supports an incentive for molecular screening platforms. PMID- 22090411 TI - Characterization and comparison of invasive Corynebacterium diphtheriae isolates from France and Poland. AB - Corynebacterium diphtheriae, the agent of diphtheria, is rarely responsible for bacteremia. However, high numbers of bacteremia have been reported in countries with extensive immunization coverage. Here, we used molecular and phenotypic tools to characterize and compare 42 invasive isolates collected in France (including New Caledonia) and Poland over a 23-year period. PMID- 22090412 TI - Validation of a large-scale audit technique for CT dose optimisation. AB - The expansion and increasing availability of computed tomography (CT) imaging means that there is a greater need for the development of efficient optimisation strategies that are able to inform clinical practice, without placing a significant burden on limited departmental resources. One of the most fundamental aspects to any optimisation programme is the collection of patient dose information, which can be compared with appropriate diagnostic reference levels. This study has investigated the implementation of a large-scale audit technique, which utilises data that already exist in the radiology information system, to determine typical doses for a range of examinations on four CT scanners. This method has been validated against what is considered the 'gold standard' technique for patient dose audits, and it has been demonstrated that results equivalent to the 'standard-sized patient' can be inferred from this much larger data set. This is particularly valuable where CT optimisation is concerned as it is considered a 'high dose' technique, and hence close monitoring of patient dose is particularly important. PMID- 22090413 TI - Natural activity concentrations in bottled drinking water and consequent doses. AB - The radioactivity concentrations of nuclides (238)U, (232)Th and (40)K in bottled drinking water from six different manufacturers from Turkey were measured using high-resolution gamma-ray spectrometry. The measurement was done using a coaxial high-purity germanium detector system coupled to Ortec-Dspect jr digital MCA system. The average measured activity concentrations of the nuclides (238)U, (232)Th and (40)K are found to be 0.781, 1.05 and 2.19 Bq l(-1), respectively. The measured activity concentrations have been compared with similar studies from different locations. The annual effective doses for ingestion of radionuclides in the water are found to be 0.0246 mSv for (238)U and 0.169 mSv for (232)Th. PMID- 22090414 TI - A survey on performance status of mammography machines: image quality and dosimetry studies using a standard mammography imaging phantom. AB - It is essential to perform quality control (QC) tests on mammography equipment in order to produce an appropriate image quality at a lower radiation dose to patients. Imaging and dosimetric measurements on 15 mammography machines located at the busiest radiology centres of Mumbai, India were carried out using a standard CIRS breast imaging phantom in order to see the level of image quality and breast doses. The QC tests include evaluations of image quality and the mean glandular doses (MGD), which is derived from the breast entrance exposure, half value layer (HVL), compressed breast thickness (CBT) and breast tissue compositions. At the majority of the centres, film-processing and darkroom conditions were not found to be maintained, which is required to meet the technical development specifications for the mammography film in use as recommended by the American College of Radiology (ACR). In most of the surveyed centres, the viewbox luminance and room illuminance conditions were not found to be in line with the mammography requirements recommended by the ACR. The measured HVL values of the machines were in the range of 0.27-0.39 mm aluminium (Al) with a mean value of 0.33+/-0.04 mm Al at 28 kV(p) following the recommendation provided by ACR. The measured MGDs were in the range of 0.14-3.80 mGy with a mean value of 1.34 mGy. The measured MGDs vary between centre to centre by a factor of 27.14. Referring to patient doses and image quality, it was observed that only one mammography centre has exceeded the recommended MGD, i.e. 3.0 mGy per view with the value of 3.80 mGy and at eight mammography centres the measured central background density (CBD) values for mammography phantom image are found to be less than the recommended CBD limit value of 1.2-2.0 optical density. PMID- 22090415 TI - Environmental radioactivity measurements in Greece following the Fukushima Daichi nuclear accident. AB - Since the double disaster of the 9.0 magnitude earthquake and tsunami that affected hundreds of thousands of people and seriously damaged the Fukushima Daichi power plant in Japan on 11 March 2011, traces of radioactive emissions from Fukushima have spread across the entire northern hemisphere. The radioactive isotope of iodine (131)I that was generated by the nuclear accident in Fukushima arrived in Greece on 24 March 2011. Radioactive iodine is present in the air either as gas or bound to particles (aerosols). The maximum (131)I concentrations were measured between 3 and 5 April 2011. In aerosols the maximum (131)I values measured in Southern Greece (Athens) and Northern Greece (Thessaloniki) were 585+/-70 and 408+/-61 MUBetaq m(-3), respectively. (131)I concentrations in gas were about 3.5 times higher than in aerosols. Since 29 April 2011, the (131)I concentration has been below detection limits. Traces of (137)Cs and (134)Cs were also measured in the air filters with an activity ratio of (137)Cs/(134)Cs equal to 1 and (131)I/(137)Cs activity ratio of about 3. Since 16 May 2011, the (137)Cs concentration in air has been determined to be about the same as before the Fukushima accident. Traces of (131)I were also measured in grass and milk. The maximum measured activity of (131)I in sheep milk was about 2 Bq l(-1) which is 5000 times less than that measured in Greece immediately after the Chernobyl accident. The measured activity concentrations of artificial radionuclides in Greece due to the Fukushima release, have been very low, with no impact on human health. PMID- 22090416 TI - Estimation of intakes of 131I, 137Cs and 134Cs after the Chernobyl accident. AB - Activities of (131)I and (137)Cs excreted in urine from two healthy males during May 1986, when contaminated air masses from Chernobyl arrived on the territory of the Czech Republic, were determined by bioassay. The data were used to estimate the intakes and committed effective doses from these radionuclides. The results for inhalation intakes are of particular interest, in the absence of sufficient contemporary data for airborne activity. They are found to be higher than initial estimates based on air sampling. PMID- 22090417 TI - Dosimetric investigation of the solar erythemal UV radiation protection provided by beards and moustaches. AB - A dosimetric technique has been employed to establish the amount of erythemal ultraviolet radiation (UVR) protection provided by facial hair considering the influence of solar zenith angle (SZA) and beard-moustache length. The facial hair reduced the exposure ratios (ERs) to approximately one-third of those to the sites with no hair. The variation in the ERs over the different sites was reduced compared with the cases with no beard. The ultraviolet protection factor (UPF) provided by the facial hair ranged from 2 to 21. The UPF decreases with increasing SZA. The minimum UPF was in the 53-62 degrees range. The longer hair provides a higher UPF at the smaller SZA, but the difference between the protection provided by the longer hair compared with the shorter hair reduces with increasing SZA. Protection from UVR is provided by the facial hair; however, it is not very high, particularly at the higher SZA. PMID- 22090418 TI - Measurement of gastric emptying time of solids in healthy subjects using scintigraphic method: a revised technique. AB - The gastric emptying half time (GET) of solid food in 24 healthy volunteers (11M/13F) was evaluated using a revised technique and a gamma camera scan. Within 20 min and after 8 h of fasting, each volunteer ate two pieces of toast with a two-egg-omelette that was mixed with 18.5 MBq (99m)Tc-labelled phytate. The raw data were analysed in the MATLAB program to establish the gastric intestine tract (GI tract) biokinetic model. The GI tract model defines the metabolic mechanism with reference to five compartments, which are stomach, body fluid, small intestine (SI), upper large intestine and lower large intestine, according to the ICRP-30 report. The model was expressed using four simultaneous time-dependent differential equations. The gastric emptying half-time and T(1/2eff)(SI) of males were 62.6+/-15.4 and 149.8+/-204.1 min, respectively, and those of females were 98.8+/-16.3 and 131.6+/-38.4 min. PMID- 22090419 TI - Plumbagin inhibits osteoclastogenesis and reduces human breast cancer-induced osteolytic bone metastasis in mice through suppression of RANKL signaling. AB - Bone loss is one of the major complications of advanced cancers such as breast cancer, prostate cancer, and multiple myeloma; agents that can suppress this bone loss have therapeutic potential. Extensive research within the last decade has revealed that RANKL, a member of the tumor necrosis factor superfamily, plays a major role in cancer-associated bone resorption and thus is a therapeutic target. We investigated the potential of vitamin K3 analogue plumbagin (derived from Chitrak, an Ayurvedic medicinal plant) to modulate RANKL signaling, osteoclastogenesis, and breast cancer-induced osteolysis. Plumbagin suppressed RANKL-induced NF-kappaB activation in mouse monocytes, an osteoclast precursor cell, through sequential inhibition of activation of IkappaBalpha kinase, IkappaBalpha phosphorylation, and IkappaBalpha degradation. Plumbagin also suppressed differentiation of these cells into osteoclasts induced either by RANKL or by human breast cancer or human multiple myeloma cells. When examined for its ability to prevent human breast cancer-induced bone loss in animals, plumbagin (2 mg/kg body weight) administered via the intraperitoneal route significantly decreased osteolytic lesions, resulting in preservation of bone volume in nude mice bearing human breast tumors. Overall, our results indicate that plumbagin, a vitamin K analogue, is a potent inhibitor of osteoclastogenesis induced by tumor cells and of breast cancer-induced osteolytic metastasis through suppression of RANKL signaling. PMID- 22090420 TI - Single-chain antibody-based immunotoxins targeting Her2/neu: design optimization and impact of affinity on antitumor efficacy and off-target toxicity. AB - Recombinant immunotoxins, consisting of single-chain variable fragments (scFv) genetically fused to polypeptide toxins, represent potentially effective candidates for cancer therapeutics. We evaluated the affinity of various anti Her2/neu scFv fused to recombinant gelonin (rGel) and its effect on antitumor efficacy and off-target toxicity. A series of rGel-based immunotoxins were created from the human anti-Her2/neu scFv C6.5 and various affinity mutants (designated ML3-9, MH3-B1, and B1D3) with affinities ranging from 10(-8) to 10( 11) mol/L. Against Her2/neu-overexpressing tumor cells, immunotoxins with increasing affinity displayed improved internalization and enhanced autophagic cytotoxicity. Targeting indices were highest for the highest affinity B1D3/rGel construct. However, the addition of free Her2/neu extracellular domain (ECD) significantly reduced the cytotoxicity of B1D3/rGel because of immune complex formation. In contrast, ECD addition had little impact on the lower affinity constructs in vitro. In vivo studies against established BT474 M1 xenografts showed growth suppression by all immunotoxins. Surprisingly, therapy with the B1D3-rGel induced significant liver toxicity because of immune complex formation with shed Her2/neu antigen in circulation. The MH3-B1/rGel construct with intermediate affinity showed effective tumor growth inhibition without inducing hepatotoxicity or complex formation. These findings show that while high-affinity constructs can be potent antitumor agents, they may also be associated with mistargeting through the facile formation of complexes with soluble antigen leading to significant off-target toxicity. Constructs composed of intermediate affinity antibodies are also potent agents that are more resistant to immune complex formation. Therefore, affinity is an exceptionally important consideration when evaluating the design and efficacy of targeted therapeutics. PMID- 22090421 TI - In silico screening reveals structurally diverse, nanomolar inhibitors of NQO2 that are functionally active in cells and can modulate NF-kappaB signaling. AB - The National Cancer Institute chemical database has been screened using in silico docking to identify novel nanomolar inhibitors of NRH:quinone oxidoreductase 2 (NQO2). The inhibitors identified from the screen exhibit a diverse range of scaffolds and the structure of one of the inhibitors, NSC13000 cocrystalized with NQO2, has been solved. This has been used to aid the generation of a structure activity relationship between the computationally derived binding affinity and experimentally measured enzyme inhibitory potency. Many of the compounds are functionally active as inhibitors of NQO2 in cells at nontoxic concentrations. To show this, advantage was taken of the NQO2-mediated toxicity of the chemotherapeutic drug CB1954. The toxicity of this drug is substantially reduced when the function of NQO2 is inhibited, and many of the compounds achieve this in cells at nanomolar concentrations. The NQO2 inhibitors also attenuated TNFalpha mediated, NF-kB-driven transcriptional activity. The link between NQO2 and the regulation of NF-kB was confirmed by using short interfering RNA to NQO2 and by the observation that NRH, the cofactor for NQO2 enzyme activity, could regulate NF-kB activity in an NQO2-dependent manner. NF-kB is a potential therapeutic target and this study reveals an underlying mechanism that may be usable for developing new anticancer drugs. PMID- 22090422 TI - Tuberin and PRAS40 are anti-apoptotic gatekeepers during early human amniotic fluid stem-cell differentiation. AB - Embryoid bodies (EBs) are three-dimensional multicellular aggregates allowing the in vitro investigation of stem-cell differentiation processes mimicking early embryogenesis. Human amniotic fluid stem (AFS) cells harbor high proliferation potential, do not raise the ethical issues of embryonic stem cells, have a lower risk for tumor development, do not need exogenic induction of pluripotency and are chromosomal stable. Starting from a single human AFS cell, EBs can be formed accompanied by the differentiation into cells of all three embryonic germ layers. Here, we report that siRNA-mediated knockdown of the endogenous tuberous sclerosis complex-2 (TSC2) gene product tuberin or of proline-rich Akt substrate of 40 kDa (PRAS40), the two major negative regulators of mammalian target of rapamycin (mTOR), leads to massive apoptotic cell death during EB development of human AFS cells without affecting the endodermal, mesodermal and ectodermal cell differentiation spectrum. Co-knockdown of endogenous mTOR demonstrated these effects to be mTOR-dependent. Our findings prove this enzyme cascade to be an essential anti-apoptotic gatekeeper of stem-cell differentiation during EB formation. These data allow new insights into the regulation of early stem-cell maintenance and differentiation and identify a new role of the tumor suppressor tuberin and the oncogenic protein PRAS40 with the relevance for a more detailed understanding of the pathogenesis of diseases associated with altered activities of these gene products. PMID- 22090423 TI - Altered dopamine metabolism and increased vulnerability to MPTP in mice with partial deficiency of mitochondrial complex I in dopamine neurons. AB - A variety of observations support the hypothesis that deficiency of complex I [reduced nicotinamide-adenine dinucleotide (NADH):ubiquinone oxidoreductase] of the mitochondrial respiratory chain plays a role in the pathophysiology of Parkinson's disease (PD). However, recent data from a study using mice with knockout of the complex I subunit NADH:ubiquinone oxidoreductase iron-sulfur protein 4 (Ndufs4) has challenged this concept as these mice show degeneration of non-dopamine neurons. In addition, primary dopamine (DA) neurons derived from such mice, reported to lack complex I activity, remain sensitive to toxins believed to act through inhibition of complex I. We tissue-specifically disrupted the Ndufs4 gene in mouse heart and found an apparent severe deficiency of complex I activity in disrupted mitochondria, whereas oxidation of substrates that result in entry of electrons at the level of complex I was only mildly reduced in intact isolated heart mitochondria. Further analyses of detergent-solubilized mitochondria showed the mutant complex I to be unstable but capable of forming supercomplexes with complex I enzyme activity. The loss of Ndufs4 thus causes only a mild complex I deficiency in vivo. We proceeded to disrupt Ndufs4 in midbrain DA neurons and found no overt neurodegeneration, no loss of striatal innervation and no symptoms of Parkinsonism in tissue-specific knockout animals. However, DA homeostasis was abnormal with impaired DA release and increased levels of DA metabolites. Furthermore, Ndufs4 DA neuron knockouts were more vulnerable to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Taken together, these findings lend in vivo support to the hypothesis that complex I deficiency can contribute to the pathophysiology of PD. PMID- 22090424 TI - DelK32-lamin A/C has abnormal location and induces incomplete tissue maturation and severe metabolic defects leading to premature death. AB - The LMNA gene encodes lamin A/C intermediate filaments that polymerize beneath the nuclear membrane, and are also found in the nucleoplasm in an uncharacterized assembly state. They are thought to have structural functions and regulatory roles in signaling pathways via interaction with transcription factors. Mutations in LMNA have been involved in numerous inherited human diseases, including severe congenital muscular dystrophy (L-CMD). We created the Lmna(DeltaK32) knock-in mouse harboring a L-CMD mutation. Lmna(DeltaK32/DeltaK32) mice exhibited striated muscle maturation delay and metabolic defects, including reduced adipose tissue and hypoglycemia leading to premature death. The level of mutant proteins was markedly lower in Lmna(DeltaK32/DeltaK32), and while wild-type lamin A/C proteins were progressively relocated from nucleoplasmic foci to the nuclear rim during embryonic development, mutant proteins were maintained in nucleoplasmic foci. In the liver and during adipocyte differentiation, expression of DeltaK32-lamin A/C altered sterol regulatory element binding protein 1 (SREBP-1) transcriptional activities. Taken together, our results suggest that lamin A/C relocation at the nuclear lamina seems important for tissue maturation potentially by releasing its inhibitory function on transcriptional factors, including but not restricted to SREBP-1. And importantly, L-CMD patients should be investigated for putative metabolic disorders. PMID- 22090425 TI - Biochemical studies of the Saccharomyces cerevisiae Mph1 helicase on junction containing DNA structures. AB - Saccharomyces cerevisiae Mph1 is a 3-5' DNA helicase, required for the maintenance of genome integrity. In order to understand the ATPase/helicase role of Mph1 in genome stability, we characterized its helicase activity with a variety of DNA substrates, focusing on its action on junction structures containing three or four DNA strands. Consistent with its 3' to 5' directionality, Mph1 displaced 3'-flap substrates in double-fixed or equilibrating flap substrates. Surprisingly, Mph1 displaced the 5'-flap strand more efficiently than the 3' flap strand from double-flap substrates, which is not expected for a 3-5' DNA helicase. For this to occur, Mph1 required a threshold size (>5 nt) of 5' single-stranded DNA flap. Based on the unique substrate requirements of Mph1 defined in this study, we propose that the helicase/ATPase activity of Mph1 play roles in converting multiple-stranded DNA structures into structures cleavable by processing enzymes such as Fen1. We also found that the helicase activity of Mph1 was used to cause structural alterations required for restoration of replication forks stalled due to damaged template. The helicase properties of Mph1 reported here could explain how it resolves D loop structure, and are in keeping with a model proposed for the error-free damage avoidance pathway. PMID- 22090427 TI - Silk-hyaluronan-based composite hydrogels: a novel, securable vehicle for drug delivery. AB - A new, biocompatible hyaluronic acid (HA)-silk hydrogel composite was fabricated and tested for use as a securable drug delivery vehicle. The composite consisted of a hydrogel formed by cross-linking thiol-modified HA with poly(ethylene glycol)-diacrylate, within which was embedded a reinforcing mat composed of electrospun silk fibroin protein. Both HA and silk are biocompatible, selectively degradable biomaterials with independently controllable material properties. Mechanical characterization showed the composite tensile strength as fabricated to be 4.43 +/- 2.87 kPa, two orders of magnitude above estimated tensions found around potential target organs. In the presence of hyaluronidase (HAse) in vitro, the rate of gel degradation increased with enzyme concentration although the reinforcing silk mesh was not digested. Composite gels demonstrated the ability to store and sustainably deliver therapeutic agents. Time constants for in vitro release of selected representative antibacterial and anti-inflammatory drugs varied from 46.7 min for cortisone to 418 min for hydrocortisone. This biocomposite showed promising mechanical characteristics for direct fastening to tissue and organs, as well as controllable degradation properties suitable for storage and release of therapeutically relevant drugs. PMID- 22090426 TI - Structural analysis of an eIF3 subcomplex reveals conserved interactions required for a stable and proper translation pre-initiation complex assembly. AB - Translation initiation factor eIF3 acts as the key orchestrator of the canonical initiation pathway in eukaryotes, yet its structure is greatly unexplored. We report the 2.2 A resolution crystal structure of the complex between the yeast seven-bladed beta-propeller eIF3i/TIF34 and a C-terminal alpha-helix of eIF3b/PRT1, which reveals universally conserved interactions. Mutating these interactions displays severe growth defects and eliminates association of eIF3i/TIF34 and strikingly also eIF3g/TIF35 with eIF3 and 40S subunits in vivo. Unexpectedly, 40S-association of the remaining eIF3 subcomplex and eIF5 is likewise destabilized resulting in formation of aberrant pre-initiation complexes (PICs) containing eIF2 and eIF1, which critically compromises scanning arrest on mRNA at its AUG start codon suggesting that the contacts between mRNA and ribosomal decoding site are impaired. Remarkably, overexpression of eIF3g/TIF35 suppresses the leaky scanning and growth defects most probably by preventing these aberrant PICs to form. Leaky scanning is also partially suppressed by eIF1, one of the key regulators of AUG recognition, and its mutant sui1(G107R) but the mechanism differs. We conclude that the C-terminus of eIF3b/PRT1 orchestrates co operative recruitment of eIF3i/TIF34 and eIF3g/TIF35 to the 40S subunit for a stable and proper assembly of 48S pre-initiation complexes necessary for stringent AUG recognition on mRNAs. PMID- 22090428 TI - Preparation of photosensitizer-loaded PLLA nanofibers and its anti-tumor effect for photodynamic therapy in vitro. AB - Photodynamic therapy (PDT) is a promising new treatment for cancer that has been recently accepted clinically. PDT is based on the administration of tumor localizing photosensitizers (PSs), followed by exposing the neoplastic area to the light absorbed by the PS. In this article, a novel anticancer nanofiber membrane containing purpurin-18 (0.1%) was successfully prepared. The thickness of membrane was 0.028 mm, and the average fiber diameter was around 357 nm by scanning electron microscope (SEM). It was indicated that purpurin-18 possessed excellent compatibility with PLLA from FTIR spectrum. The physical properties of fiber membrane were also characterized by Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD). Cell morphology and the interaction between cells and nanofibers were studied by SEM. The results showed that both SMMC 7721 and ECA109 cells can adhere and spread on the surface of the polymer nanofiber, and both cells can interact and integrate well with the surrounding fibers. The efficacy of PDT was determined by MTT assays. The results showed that the cells were killed immediately after PDT and purpurin-18 had no different efficacy to different cancer cell lines. In summary, the PS-loaded PLLA nanofibers were prepared successfully, and the SMMC 7721 and ECA109 cells could be inhibited and killed through photodynamic therapy. PMID- 22090429 TI - Assessment of oxidative stress and chromosomal aberration inducing potential of three medical grade silicone polymer materials. AB - Medical expenditures for devices are increasing along with the ageing of human population and the synthesis of materials such as silicone polymers is on upsurge for manufacturing these devices. The International Organization for Standardization (ISO) emphasizes a battery of tests for preclinical assessment of biocompatibility of medical devices. Genotoxicity assays have become an integral component of these test procedures and it employs a set of in vitro and in vivo experiments to detect mutagens. Hence, this study was performed with an intention to investigate the genotoxic potential of the physiological saline extracts of three medical grade silicone polymer materials by the in vitro chromosomal aberration assay using human peripheral blood lymphocytes. Further, the oxidative stress inducing potential of the material extracts was investigated in vivo in mice liver homogenates using cyclophosphamide as positive control. The investigation revealed that none of the three materials were able to produce marked human lymphocyte chromosomal aberration, suggesting the absence of mutagens. The materials also showed negative results in their oxidative stress inducing potential, which was revealed by the normal levels of lipid peroxidation and unaltered levels of glutathione and its metabolizing enzymes in the mice liver tissue homogenates. It was interesting to observe a significant correlation between the genotoxic and antioxidant parameters investigated. Hence, it is suggested that the estimation of antioxidant status would serve as a better preliminary testing procedure prior to evaluating the genetic and molecular toxicity mechanisms of medical devices and/or materials intended for manufacture of such devices. PMID- 22090430 TI - Cell survival and proliferation after encapsulation in a chemically modified Pluronic(R) F127 hydrogel. AB - Pluronic(r) F127 is a biocompatible, injectable, and thermoresponsive polymer with promising biomedical applications. In this study, a chemically modified form, i.e., Pluronic ALA-L with tailored degradation rate, was tested as an encapsulation vehicle for osteoblastic cells. UV cross-linking of the modified polymer results in a stable hydrogel with a slower degradation rate. Toxicological screening showed no adverse effects of the modified Pluronic ALA-L on the cell viability. Moreover, high viability of embedded cells in the cross linked Pluronic ALA-L was observed with life/death fluorescent staining during a 7-day-culture period. Cells were also cultured on macroporous, cross-linked gelatin microbeads, called CultiSpher-S(r) carriers, and encapsulated into the modified cross-linked hydrogel. Also, in this situation, good cell proliferation and migration could be observed in vitro. Preliminary in vivo tests have shown the formation of new bone starting from the injected pre-loaded CultiSpher-S(r) carriers. PMID- 22090431 TI - Effects of plasma surface treatments of diamond-like carbon and polymeric substrata on the cellular behavior of human fibroblasts. AB - Surface properties play an important role in the functioning of a biomaterial in the biological environment. This work describes the influence of the changes that occurred on diamond-like carbon (DLC) and polymeric substrata by different nitrogen and ammonia plasmas treatments and its effects on the cell proliferation on these materials. All substrata were additionally subjected to the effect of neutral beams of nitrogen atoms and NH species for comparison purposes. Results about the proliferation, viability, and morphology of fibroblasts were correlated with surface chemical composition, surface tension, and topography. It was found that the presence of amine groups on the surface and the surface tension are beneficial factors for the cell growth. Surface roughness in DLC also plays a positive role in favoring cell adhesion and proliferation, but it can be detrimental for some of the treated polymers because of the accumulation of low molecular weight fragments formed as a result of the plasma treatments. Analysis of the overall results for each type of material allowed to define a unique parameter called 'factor of merit' accounting for the influence of the different surface characteristics on the cell deployment, which can be used to predict qualitatively the efficiency for cell growth. PMID- 22090432 TI - Bone substitute materials delivering zoledronic acid: physicochemical characterization, drug load, and release properties. AB - Calcium phosphate-like bone substitute materials have a long history of successful orthopedic applications such as bone void filling and augmentation. Based on the clinical indications, these materials may be loaded with active agents by adsorption offering a perspective for providing innovative drug delivery systems. The highly effective bisphosphonate zoledronic acid (ZOL) demonstrated a strong affinity to biominerals and is known to significantly reduce osteoclastic activity. Support of early bone formation and reduction of bone resorption can be promoted after implantation of bioceramics releasing ZOL. The aim of this study was to develop an easy to handle approach to combine ZOL with bone substitutes by use of a dipping technique. The properties of three different materials were investigated by using a number of physicochemical methods such as light microscopy, scanning electron microscopy (SEM), dynamic vapor sorption (DVS), true density, and surface area measurement to evaluate the feasibility of being potential drug carriers. Besides physicochemical characterization, the bone substitutes were evaluated by their ZOL-loading capacity in a time- and concentration-dependent manner. Additionally, the materials were assessed as release systems in an in vitro study. A controlled ZOL load in a range of 0.04-1.86 ug/mg material and a release of 0.02-0.18 ug/mg within 30 min is demonstrated. The findings support using the investigated bioceramics as carrier systems to release ZOL. Overall, the results create the base for further development of drug-delivery systems with controlled drug loading and prolonged release and need to be further analyzed in an in vivo study. PMID- 22090433 TI - Stratified scaffolds for osteochondral tissue engineering applications: electrospun PDLLA nanofibre coated Bioglass(r)-derived foams. AB - This work focuses on designing bilayered constructs by combining electrospun poly DL-Lactide (PDLLA) fibers and Bioglass(r)-derived scaffolds for development of osteochondral tissue replacement materials. Electrospinning was carried out using a solution of 5 wt/v% PDLLA in dimethyl carbonate. The PDLLA layer thickness increased from 2 to 150 um with varying electrospinning time. Bioactivity studies in simulated body fluid showed that HA mineralization decreased as the thickness of the PDLLA layer increased. A preliminary in vitro study using chondrocyte cells (ATDC5) showed that cells attached, proliferated and migrated into the fibrous network, confirming the potential applicability of the bilayered scaffolds in osteochondral defect regeneration. PMID- 22090434 TI - Osteogenesis of human mesenchymal stem cells on micro-patterned surfaces. AB - Osteogenic responses of human mesenchymal stromal cells (hMSCs) were compared on square-patterned, inverse square-patterned, and planar titanium, chromium, diamond-like carbon (DLC), and tantalum; hypothesis was that both the materials and patterns affect osteogenesis. Samples were produced using photolithography and physical vapor deposition. Early-marker alkaline phosphatase (ALP) and mid markers, small body size and mothers against decapentaplegic-related protein-1 (SMAD1), runt-related transcription factor-2 (RUNX2), and osteopontin were studied using quantitative real-time polymerase chain reaction. ALP and hydroxyapatite, were colorimetrically studied. ALP reached highest values on both patterned titanium samples, but mid-markers disclosed that it was already lagging behind planar and inverse patterned tantalum. Hydroxyapatite formation disclosed that osteo-induced hMSCs passed all the differentiation stages (except on planar chromium). Presence of hydroxyapatite disclosed that both types of patterning promoted (p < 0.001) osteogenesis compared to planar samples. Results suggest that the osseocompatibility/integration of implants could be improved by changing the monotonous and featureless implant-host interface into micro-patterned interface to provide physical differentiation cues. PMID- 22090435 TI - The 'Green Revolution' dwarfing genes play a role in disease resistance in Triticum aestivum and Hordeum vulgare. AB - The Green Revolution dwarfing genes, Rht-B1b and Rht-D1b, encode mutant forms of DELLA proteins and are present in most modern wheat varieties. DELLA proteins have been implicated in the response to biotic stress in the model plant, Arabidopsis thaliana. Using defined wheat Rht near-isogenic lines and barley Sln1 gain of function (GoF) and loss of function (LoF) lines, the role of DELLA in response to biotic stress was investigated in pathosystems representing contrasting trophic styles (biotrophic, hemibiotrophic, and necrotrophic). GoF mutant alleles in wheat and barley confer a resistance trade-off with increased susceptibility to biotrophic pathogens and increased resistance to necrotrophic pathogens whilst the converse was conferred by a LoF mutant allele. The polyploid nature of the wheat genome buffered the effect of single Rht GoF mutations relative to barley (diploid), particularly in respect of increased susceptibility to biotrophic pathogens. A role for DELLA in controlling cell death responses is proposed. Similar to Arabidopsis, a resistance trade-off to pathogens with contrasting pathogenic lifestyles has been identified in monocotyledonous cereal species. Appreciation of the pleiotropic role of DELLA in biotic stress responses in cereals has implications for plant breeding. PMID- 22090437 TI - Response of barley plants to Fe deficiency and Cd contamination as affected by S starvation. AB - Both Fe deficiency and Cd exposure induce rapid changes in the S nutritional requirement of plants. The aim of this work was to characterize the strategies adopted by plants to cope with both Fe deficiency (release of phytosiderophores) and Cd contamination [production of glutathione (GSH) and phytochelatins] when grown under conditions of limited S supply. Experiments were performed in hydroponics, using barley plants grown under S sufficiency (1.2 mM sulphate) and S deficiency (0 mM sulphate), with or without Fe(III)-EDTA at 0.08 mM for 11 d and subsequently exposed to 0.05 mM Cd for 24 h or 72 h. In S-sufficient plants, Fe deficiency enhanced both root and shoot Cd concentrations and increased GSH and phytochelatin levels. In S-deficient plants, Fe starvation caused a slight increase in Cd concentration, but this change was accompanied neither by an increase in GSH nor by an accumulation of phytochelatins. Release of phytosiderophores, only detectable in Fe-deficient plants, was strongly decreased by S deficiency and further reduced after Cd treatment. In roots Cd exposure increased the expression of the high affinity sulphate transporter gene (HvST1) regardless of the S supply, and the expression of the Fe deficiency-responsive genes, HvYS1 and HvIDS2, irrespective of Fe supply. In conclusion, adequate S availability is necessary to cope with Fe deficiency and Cd toxicity in barley plants. Moreover, it appears that in Fe-deficient plants grown in the presence of Cd with limited S supply, sulphur may be preferentially employed in the pathway for biosynthesis of phytosiderophores, rather than for phytochelatin production. PMID- 22090436 TI - Arabidopsis CSP41 proteins form multimeric complexes that bind and stabilize distinct plastid transcripts. AB - The spinach CSP41 protein has been shown to bind and cleave chloroplast RNA in vitro. Arabidopsis thaliana, like other photosynthetic eukaryotes, encodes two copies of this protein. Several functions have been described for CSP41 proteins in Arabidopsis, including roles in chloroplast rRNA metabolism and transcription. CSP41a and CSP41b interact physically, but it is not clear whether they have distinct functions. It is shown here that CSP41b, but not CSP41a, is an essential and major component of a specific subset of RNA-binding complexes that form in the dark and disassemble in the light. RNA immunoprecipitation and hybridization to gene chips (RIP-chip) experiments indicated that CSP41 complexes can contain chloroplast mRNAs coding for photosynthetic proteins and rRNAs (16S and 23S), but no tRNAs or mRNAs for ribosomal proteins. Leaves of plants lacking CSP41b showed decreased steady-state levels of CSP41 target RNAs, as well as decreased plastid transcription and translation rates. Representative target RNAs were less stable when incubated with broken chloroplasts devoid of CSP41 complexes, indicating that CSP41 proteins can stabilize target RNAs. Therefore, it is proposed that (i) CSP41 complexes may serve to stabilize non-translated target mRNAs and precursor rRNAs during the night when the translational machinery is less active in a manner responsive to the redox state of the chloroplast, and (ii) that the defects in translation and transcription in CSP41 protein-less mutants are secondary effects of the decreased transcript stability. PMID- 22090438 TI - Phosphorylation of serine residues in the N-terminus modulates the activity of ACA8, a plasma membrane Ca2+-ATPase of Arabidopsis thaliana. AB - ACA8 is a plasma membrane-localized isoform of calmodulin (CaM)-regulated Ca(2+) ATPase of Arabidopsis thaliana. Several phosphopeptides corresponding to portions of the regulatory N-terminus of ACA8 have been identified in phospho-proteomic studies. To mimic phosphorylation of the ACA8 N-terminus, each of the serines found to be phosphorylated in those studies (Ser19, Ser22, Ser27, Ser29, Ser57, and Ser99) has been mutated to aspartate. Mutants have been expressed in Saccharomyces cerevisiae and characterized: mutants S19D and S57D--and to a lesser extent also mutants S22D and S27D--are deregulated, as shown by their low activation by CaM and by tryptic cleavage of the N-terminus. The His-tagged N termini of wild-type and mutant ACA8 (6His-(1)M-I(116)) were expressed in Escherichia coli, affinity-purified, and used to analyse the kinetics of CaM binding by surface plasmon resonance. All the analysed mutations affect the kinetics of interaction with CaM to some extent: in most cases, the altered kinetics result in marginal changes in affinity, with the exception of mutants S57D (K(D) ~ 10-fold higher than wild-type ACA8) and S99D (K(D) about half that of wild-type ACA8). The ACA8 N-terminus is phosphorylated in vitro by two isoforms of A. thaliana calcium-dependent protein kinase (CPK1 and CPK16); phosphorylation of mutant 6His-(1)M-I(116) peptides shows that CPK16 is able to phosphorylate the ACA8 N-terminus at Ser19 and at Ser22. The possible physiological implications of the subtle modulation of ACA8 activity by phosphorylation of its N-terminus are discussed. PMID- 22090439 TI - A male sterility-associated cytotoxic protein ORF288 in Brassica juncea causes aborted pollen development. AB - Cytoplasmic male sterility (CMS) is a widespread phenomenon in higher plants, and several studies have established that this maternally inherited defect is often associated with a mitochondrial mutant. Approximately 10 chimeric genes have been identified as being associated with corresponding CMS systems in the family Brassicaceae, but there is little direct evidence that these genes cause male sterility. In this study, a novel chimeric gene (named orf288) was found to be located downstream of the atp6 gene and co-transcribed with this gene in the hau CMS sterile line. Western blotting analysis showed that this predicted open reading frame (ORF) was translated in the mitochondria of male-sterile plants. Furthermore, the growth of Escherichia coli was significantly repressed in the presence of ORF288, which indicated that this protein is toxic to the E. coli host cells. To confirm further the function of orf288 in male sterility, the gene was fused to a mitochondrial-targeting pre-sequence under the control of the Arabidopsis APETALA3 promoter and introduced into Arabidopsis thaliana. Almost 80% of transgenic plants with orf288 failed to develop anthers. It was also found that the independent expression of orf288 caused male sterility in transgenic plants, even without the transit pre-sequence. Furthermore, transient expression of orf288 and green fluorescent protein (GFP) as a fused protein in A. thaliana protoplasts showed that ORF288 was able to anchor to mitochondria even without the external mitochondrial-targeting peptide. These observations provide important evidence that orf288 is responsible for the male sterility of hau CMS in Brassica juncea. PMID- 22090440 TI - Capitalizing on deliberate, accidental, and GM-driven environmental change caused by crop modification. AB - The transgenic traits associated with the majority of commercial genetically modified crops are focused on improving herbicide and insecticide management practices. The use of the transgenic technology in these crops and the associated chemistry has been the basis of studies that provide evidence for occasional improvement in environmental benefits due to the use of less residual herbicides, more targeted pesticides, and reduced field traffic. This is nicely exemplified through studies using Environmental Impact Quotient (EIQ) assessments. Whilst EIQ evaluations may sometimes illustrate environmental benefits they have their limitations. EIQ evaluations are not a surrogate for Environmental Risk Assessments and may not reflect real environmental interactions between crops and the environment. Addressing the impact cultivated plants have on the environment generally attracts little public attention and research funding, but the introduction of GM has facilitated an expansion of research to address potential environmental concerns from government, NGOs, industry, consumers, and growers. In this commentary, some evidence from our own research and several key papers that highlight EIQ assessments of the impact crops are having on the environment are presented. This information may be useful as an education tool on the potential benefits of GM and conventional farming. In addition, other deliberate, accidental, and GM-driven benefits derived from the examination of GM cropping systems is briefly discussed. PMID- 22090441 TI - Tensional stress generation in gelatinous fibres: a review and possible mechanism based on cell-wall structure and composition. AB - Gelatinous fibres are specialized fibres, distinguished by the presence of an inner, gelatinous cell-wall layer. In recent years, they have attracted increasing interest since their walls have a desirable chemical composition (low lignin, low pentosan, and high cellulose contents) for applications such as saccharification and biofuel production, and they have interesting mechanical properties, being capable of generating high tensional stress. However, the unique character of gelatinous layer has not yet been widely recognized. The first part of this review presents a model of gelatinous-fibre organization and stresses the unique character of the gelatinous layer as a separate type of cell wall layer, different from either primary or secondary wall layers. The second part discusses major current models of tensional stress generation by these fibres and presents a novel unifying model based on recent advances in knowledge of gelatinous wall structure. Understanding this mechanism could potentially lead to novel biomimetic developments in material sciences. PMID- 22090442 TI - Control of barley (Hordeum vulgare L.) development and senescence by the interaction between a chromosome six grain protein content locus, day length, and vernalization. AB - Regulatory processes controlling traits such as anthesis timing and whole-plant senescence are of primary importance for reproductive success and for crop quality and yield. It has previously been demonstrated that the presence of alleles associated with high grain protein content (GPC) at a locus on barley chromosome six leads to accelerated leaf senescence, and to strong (>10-fold) up regulation of several genes which may be involved in senescence control. One of these genes (coding for a glycine-rich RNA-binding protein termed HvGR-RBP1) exhibits a high degree of similarity to Arabidopsis glycine-rich RNA-binding protein 7 (AtGRP7), which has been demonstrated to accelerate flowering under both long-day (LD) and short-day (SD) conditions, but not after vernalization. Development of near-isogenic barley lines, differing in the allelic state of the GPC locus, was compared from the seedling stage to maturity under both SD and LD and after vernalization under LD. Intriguingly, pre-anthesis plant development [measured by leaf emergence timing and pre-anthesis (sequential) leaf senescence] was enhanced in high-GPC germplasm. Differences were more pronounced under SD than under LD, but were eliminated by vernalization, associating observed effects with floral induction pathways. By contrast, differences in post-anthesis flag leaf and whole-plant senescence between low- and high-GPC germplasm persisted under all tested conditions, indicating that the GPC locus, possibly through HvGR RBP1, impacts on both developmental stages. Detailed molecular characterization of this experimental system may allow the dissection of cross-talk between signalling pathways controlling early plant and floral development on one side, and leaf/whole-plant senescence on the other side. PMID- 22090443 TI - Enhanced sensitivity to higher ozone in a pathogen-resistant tobacco cultivar. AB - Investigations of the effects of elevated ozone (O(3)) on the virus-plant system were conducted to inform virus pathogen management strategies better. One susceptible cultivar of tobacco (Nicotiana tabacum L. cv. Yongding) and a resistant cultivar (Nicotiana tabacum L. cv. Vam) to Potato virus Y petiole necrosis strain (PVY(N)) infection were grown in open-top chambers under ambient and elevated O(3) concentrations. Above-ground biomass, foliage chlorophyll, nitrogen and total non-structural carbohydrate (TNCs), soluble protein, total amino acid (TAA) and nicotine content, and peroxidase (POD) activity were measured to estimate the effects of elevated O(3) on the impact of PVY(N) in the two cultivars. Results showed that under ambient O(3), the resistant cultivar possessed greater biomass and a lower C/N ratio after infection than the susceptible cultivar; however, under elevated O(3), the resistant cultivar lost its biomass advantage but maintained a lower C/N ratio. Variation of foliar POD activity could be explained as a resistance cost which was significantly correlated with biomass and C/N ratio of the tobacco cultivar. Chlorophyll content remained steady in the resistant cultivar but decreased significantly in the susceptible cultivar when stressors were applied. Foliar soluble protein and free amino acid content, which were related to resistance cost changes, are also discussed. This study indicated that a virus-resistant tobacco cultivar showed increased sensitivity to elevated O(3) compared to a virus-sensitive cultivar. PMID- 22090444 TI - T-DNA mutagenesis in Brachypodium distachyon. AB - During the past decade, Brachypodium distachyon has emerged as an attractive experimental system and genomics model for grass research. Numerous molecular tools and genomics resources have already been developed. Functional genomics resources, including mutant collections, expression/tiling microarray, mapping populations, and genome re-sequencing for natural accessions, are rapidly being developed and made available to the community. In this article, the focus is on the current status of systematic T-DNA mutagenesis in Brachypodium. Large collections of T-DNA-tagged lines are being generated by a community of laboratories in the context of the International Brachypodium Tagging Consortium. To date, >13 000 lines produced by the BrachyTAG programme and USDA-ARS Western Regional Research Center are available by online request. The utility of these mutant collections is illustrated with some examples from the BrachyTAG collection at the John Innes Centre-such as those in the eukaryotic initiation factor 4A (eIF4A) and brassinosteroid insensitive-1 (BRI1) genes. A series of other mutants exhibiting growth phenotypes is also presented. These examples highlight the value of Brachypodium as a model for grass functional genomics. PMID- 22090446 TI - High cardiovascular risk in patients with Type 2 diabetic nephropathy: the predictive role of albuminuria and glomerular filtration rate. The NID-2 Prospective Cohort Study. AB - BACKGROUND: In Type 2 diabetic patients, clinical diagnosis of diabetic nephropathy (DN) is generally based on the concomitant presence of abnormal albuminuria and severe retinopathy. In this high-risk population, cardiovascular (CV) outcome has never been evaluated. METHODS: A cohort of 742 Type 2 diabetic patients with DN from 17 national centres was selected by the presence of persistent albuminuria >= 30 mg/day and severe diabetic retinopathy and was followed prospectively. Time to CV event (CV death, non-fatal myocardial infarction, non-fatal stroke, revascularization, major amputation) was the primary composite end point and it was analysed by multivariable Cox's proportional hazards model. The interaction between albuminuria and glomerular filtration rate (GFR) was specifically investigated. RESULTS: Median follow-up was 4.6 years. Overall 242 events (26% of which fatal) were observed in 202 patients. The proportion of CV events increased from 19 to 40% as GFR declined from the highest (>= 90 mL/min/1.73 m(2)) to the lowest (<45 mL/min/1.73 m(2)) category and was equal to 25 and 33% in microalbuminuria and macroalbuminuria, respectively. In multivariable analysis, the interaction between albuminuria and GFR was statistically significant (P = 0.012). Albuminuria, indeed, had a remarkable prognostic effect in subjects with high GFR that virtually disappeared as GFR became <30 mL/min/1.73 m(2). Age, smoking habit, previous occurrence of myocardial infarction or stroke and proliferative retinopathy were all found to have a statistically significant prognostic effect on CV outcome. CONCLUSIONS: A clinically based diagnosis of DN in Type 2 diabetes allows the identification of subjects with high CV risk. Albuminuria has a relevant prognostic effect on CV morbidity and mortality; its effect is especially pronounced when GFR is normal or near normal. PMID- 22090445 TI - Identification and functional characterization of cDNAs coding for hydroxybenzoate/hydroxycinnamate glucosyltransferases co-expressed with genes related to proanthocyanidin biosynthesis. AB - Grape proanthocyanidins (PAs) play a major role in the organoleptic properties of wine. They are accumulated mainly in grape skin and seeds during the early stages of berry development. Despite the recent progress in the identification of genes involved in PA biosynthesis, the mechanisms involved in subunit condensation, galloylation, or fine regulation of the spatio-temporal composition of grape berries in PAs are still not elucidated. Two Myb transcription factors, VvMybPA1 and VvMybPA2, controlling the PA pathway have recently been identified and ectopically over-expressed in an homologous system. In addition to already known PA genes, three genes coding for glucosyltransferases were significantly differentially expressed between hairy roots over-expressing VvMybPA1 or VvMybPA2 and control lines. The involvement of these genes in PA biosynthesis metabolism is unclear. The three glucosyltransferases display high sequence similarities with other plant glucosyltransferases able to catalyse the formation of glucose esters, which are important intermediate actors for the synthesis of different phenolic compounds. Studies of the in vitro properties of these three enzymes (K(m), V(max), substrate specificity, pH sensitivity) were performed through production of recombinant proteins in E. coli and demonstrated that they are able to catalyse the formation of 1-O-acyl-Glc esters of phenolic acids but are not active on flavonoids and stilbenes. The transcripts are expressed in the early stages of grape berry development, mainly in the berry skins and seeds. The results presented here suggest that these enzymes could be involved in vivo in PA galloylation or in the synthesis of hydroxycinnamic esters. PMID- 22090447 TI - A vero cell-derived whole-virus H5N1 vaccine effectively induces neuraminidase inhibiting antibodies. AB - A Vero cell-derived whole-virus H5N1 influenza vaccine has been shown to induce neutralizing antibodies directed against the hemagglutinin (HA) protein of diverse H5N1 strains in animal studies and clinical trials. However, neuraminidase-inhibiting (NAi) antibodies can reduce viral spread and may be of particular importance in the event of an H5N1 pandemic, where immunity due to HA antibodies is likely absent in the general population. Here we demonstrate the effective induction of NAi antibody titers after H5N1 vaccination in humans. In contrast to the immune response directed toward HA, a single vaccine dose induced a strong NAi response that was not significantly boosted by a second dose, most probably due to priming by previous vaccination or infection with seasonal influenza viruses. After 2 immunizations, seroconversion rates based on antibody titers against HA and NA were similar, indicating the induction of equally strong immune responses against both proteins by this H5N1 vaccine. PMID- 22090448 TI - Evolutionary ecology of human papillomavirus: trade-offs, coexistence, and origins of high-risk and low-risk types. AB - BACKGROUND: We address the ecological and evolutionary dynamics of human papillomavirus (HPV) that lead to the dichotomy between high-risk (HR) and low risk (LR) types. We hypothesize that HPV faces an evolutionary tradeoff between persistence and per-contact transmission probability. High virion production enhances transmissibility but also provokes an immune response leading to clearance and limited persistence. Alternatively, low virion production increases persistence at the cost of diminished transmission probability per sexual contact. We propose that LR HPV types use the former strategy and that HR types use the latter. Sexual behaviors in a host population determine the success of each strategy. METHODS: We develop an evolutionary model of HPV epidemiology, which includes host sexual behavior, and we find evolutionarily stable strategies of HPV. RESULTS: A slow turnover of sexual partners favors HR HPV, whereas high frequency of partner turnover selects for LR. When both sexual behaviors exist as subcultures in a population, disruptive selection can result in the coevolution and ecological coexistence of both HR and LR HPV types. CONCLUSIONS: Our results indicate that the elimination of HR HPV through vaccines may alter the evolutionary trajectory of the remaining types and promote evolution of new HR HPV types. PMID- 22090449 TI - Induction of serine protease inhibitor 9 by Mycobacterium tuberculosis inhibits apoptosis and promotes survival of infected macrophages. AB - Our recent microarray analysis of infected human alveolar macrophages (AMs) found serine protease inhibitor 9 (PI-9) to be the most prominently expressed of a cluster of apoptosis-associated genes induced by virulent Mycobacterium tuberculosis. In the current study, we show that induction of PI-9 occurs within hours of infection with M. tuberculosis H37Rv and is maintained through 7 days of infection in both AMs and blood monocytes. Inhibition of PI-9 by small inhibitory RNA decreased M. tuberculosis-induced expression of the antiapoptotic molecule Bcl-2 and resulted in a corresponding increase in production of caspase 3, a terminal effector molecule of apoptosis. Further, PI-9 small inhibitory RNA mediated a significant reduction in the subsequent survival of M. tuberculosis within AMs. Thus PI-9 induction within human mononuclear phagocytes by virulent M. tuberculosis serves to protect these primary targets of infection from elimination by apoptosis and thereby promotes intracellular survival of the organism. PMID- 22090450 TI - Early systemic bacterial dissemination and a rapid innate immune response characterize genetic resistance to plague of SEG mice. AB - BACKGROUND: Although laboratory mice are usually highly susceptible to Yersinia pestis, we recently identified a mouse strain (SEG) that exhibited an exceptional capacity to resist bubonic plague and used it to identify immune mechanisms associated with resistance. METHODS: The kinetics of infection, circulating blood cells, granulopoiesis, lesions, and cellular populations in the spleen, and cytokine production in various tissues were compared in SEG and susceptible C57BL/6J mice after subcutaneous infection with the virulent Y. pestis CO92. RESULTS: Bacterial invasion occurred early (day 2) but was transient in SEG/Pas mice, whereas in C57BL/6J mice it was delayed but continuous until death. The bacterial load in all organs significantly correlated with the production of 5 cytokines (granulocyte colony-stimulating factor, keratinocyte-derived chemokine (KC), macrophage cationic peptide-1 (MCP-1), interleukin 1alpha, and interleukin 6) involved in monocyte and neutrophil recruitment. Indeed, higher proportions of these 2 cell types in blood and massive recruitment of F4/80(+)CD11b(-) macrophages in the spleen were observed in SEG/Pas mice at an early time point (day 2). Later times after infection (day 4) were characterized in C57BL/6J mice by destructive lesions of the spleen and impaired granulopoiesis. CONCLUSION: A fast and efficient Y. pestis dissemination in SEG mice may be critical for the triggering of an early and effective innate immune response necessary for surviving plague. PMID- 22090451 TI - The labyrinth of nuclear reprogramming. PMID- 22090452 TI - Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation. AB - Pediatric medulloblastoma is considered a highly heterogeneous disease and a new strategy of risk stratification to optimize therapeutic outcomes is required. We aimed to investigate a new risk-stratification approach based on expression profiles of medulloblastoma cohorts. We analyzed gene expression profiles of 30 primary medulloblastomas and detected strong evidence that poor survival outcome was significantly associated with mRNA expression profiles of 17p loss. However, it was not supported in independent cohorts from previously published data (n = 100). We speculated that this discrepancy might come from complex conditions of two important prognostic determinants: loss of tumor suppressors (chromosome 17p) and high expression of oncogenes c-myc (MYCC) or N-myc (MYCN). When patients were stratified into 5 or 7 subgroups based on simultaneous consideration of these 2 factors while defining the Wnt group as independent, obviously different survival expectancies were detected between the subgroups. For instance, predicted 5-year survival probabilities ranged from 19% to 81% in the 5 subgroups. We also found that age became a significant prognostic marker after adjusting for 17p, MYCC, and MYCN status. Diminished survival in age <3 years was more substantial in subgroups with high expression of MYCC, MYCN, or 17p loss but not in other subgroups, indicating that poor survival outcome might be synergistically affected by these 3 factors. Here we suggest a more tailored subgrouping system based on expression profiles of chromosome 17p, MYCC, and MYCN, which could provide the basis for a novel risk-stratification strategy in pediatric medulloblastoma. PMID- 22090453 TI - Phase II trial of vorinostat in combination with bortezomib in recurrent glioblastoma: a north central cancer treatment group study. AB - Vorinostat, a histone deacetylase (HDAC) inhibitor, has shown evidence of single agent activity in glioblastoma (GBM), and in preclinical studies, we have demonstrated significant synergistic cytotoxicity between HDAC inhibitors and proteasome inhibitors in GBM cell lines. We therefore conducted a phase II trial to evaluate the efficacy of vorinostat in combination with the proteasome inhibitor bortezomib in patients with recurrent GBM. Vorinostat was administered at a dose of 400 mg daily for 14 days of a 21-day cycle, and bortezomib was administered at a dose of 1.3 mg/m(2) intravenously on days 1, 4, 8, and 11 of the cycle. A total of 37 patients were treated, and treatment was well tolerated: grade 3, 4 nonhematologic toxicity occurred in 30% of patients and consisted mainly of fatigue (14%) and neuropathy (5%); grade 3, 4 hematologic toxicity occurred in 37% of patients and consisted of thrombocytopenia (30%), lymphopenia (4%), and neutropenia (4%). The trial was closed at the predetermined interim analysis, with 0 of 34 patients being progression-free at 6 months. One patient achieved a partial response according to the Macdonald criteria. The median time to progression for all patients was 1.5 months (range, 0.5-5.6 months), and median overall survival (OS) was 3.2 months. Patients who had received prior bevacizumab therapy had a shorter time to progression and OS, compared with those who had not. On the basis of the results of this phase II study, further evaluation of the vorinostat-bortezomib combination in GBM patients in this dose and schedule is not recommended. PMID- 22090454 TI - Enhanced didactic methods of smoking cessation training for medical students--a randomized study. AB - BACKGROUND: It is essential that medical students are adequately trained in smoking cessation. A web-based tobacco abstinence training program might supplement or replace traditional didactic methods. METHODS: One-hundred and forty third-year medical students were all provided access to a self-directed web based learning module on smoking cessation. Thereafter, they were randomly allocated to attend 1 of 4 education approaches: (a) web-based training using the same tool, (b) lecture, (c) role playing, and (d) supervised interaction with real patients. RESULTS: Success of the intervention was measured in an objective structured clinical examination. Scores were highest in Group 4 (35.9 +/- 8.7), followed by Groups 3 (35.7 +/- 6.5), 2 (33.5 +/- 9.4), and 1 (28.0 +/- 9.6; p = .007). Students in Groups 4 (60.7%) and 3 (57.7%) achieved adequate counseling skills more frequently than those in Groups 2 (34.8%) and 1 (30%; p = .043). There was no difference in the scores reflecting theoretical knowledge (p = .439). Self-assessment of cessation skills and students' satisfaction with training was significantly better in Groups 3 and 4 as compared with 1 and 2 (p < .001 and p = .006, respectively). CONCLUSIONS: Role playing and interaction with real patients are equally efficient and both more powerful learning tools than web-based learning with or without a lecture. PMID- 22090455 TI - Gamma band activity in the developing parafascicular nucleus. AB - The parafascicular nucleus (Pf) receives cholinergic input from the pedunculopontine nucleus, part of the reticular activating system involved in waking and rapid eye movement (REM) sleep, and sends projections to the cortex. We tested the hypothesis that Pf neurons fire maximally at gamma band frequency (30-90 Hz), that this mechanism involves high-threshold voltage-dependent P/Q- and N-type calcium channels, and that this activity is enhanced by the cholinergic agonist carbachol (CAR). Patch-clamped 9- to 25-day-old rat Pf neurons (n = 299) manifested a firing frequency plateau at gamma band when maximally activated (31.5 +/- 1.5 Hz) and showed gamma oscillations when voltage clamped at holding potentials above -20 mV, and the frequency of the oscillations increased significantly with age (24.6 +/- 3.8 vs. 51.6 +/- 4.4 Hz, P < 0.001) but plateaued at gamma frequencies. Cells exposed to CAR showed significantly higher frequencies early in development compared with those without CAR (24.6 +/- 3.8 vs. 41.7 +/- 4.3 Hz, P < 0.001) but plateaued with age. The P/Q-type calcium channel blocker omega-agatoxin-IVA (omega-Aga) blocked gamma oscillations, whereas the N-type blocker omega-conotoxin-GVIA (omega-CgTx) only partially decreased the power spectrum amplitude of gamma oscillations. The blocking effect of omega-Aga on P/Q-type currents and omega-CgTx on N-type currents was consistent over age. We conclude that P/Q- and N-type calcium channels appear to mediate Pf gamma oscillations during development. We hypothesize that the cholinergic input to the Pf could activate these cells to oscillate at gamma frequency, and perhaps relay these rhythms to cortical areas, thus providing a stable high-frequency state for "nonspecific" thalamocortical processing. PMID- 22090456 TI - Neural prediction of complex accelerations for object interception. AB - To intercept or avoid moving objects successfully, we must compensate for the sensorimotor delays associated with visual processing and motor movement. Although straightforward in the case of constant velocity motion, it is unclear how humans compensate for accelerations, as our visual system is relatively poor at detecting changes in velocity. Work on free-falling objects suggests that we are able to predict the effects of gravity, but this represents the most simple, limiting case in which acceleration is constant and motion linear. Here, we show that an internal model also predicts the effects of complex, varying accelerations when they result from lawful interactions with the environment. Participants timed their responses with the arrival of a ball rolling within a tube of various shapes. The pattern of errors indicates that participants were able to compensate for most of the effects of the ball acceleration (~85%) within a relatively short practice (~300 trials). Errors on catch trials in which the ball velocity was unexpectedly maintained constant further confirmed that participants were expecting the effect of acceleration induced by the shape of the tube. A similar effect was obtained when the visual scene was projected upside down, indicating that the mechanism of this prediction is flexible and not confined to ecologically valid interactions. These findings demonstrate that the brain is able to predict motion on the basis of prior experience of complex interactions between an object and its environment. PMID- 22090457 TI - Age-dependent effect of hearing loss on cortical inhibitory synapse function. AB - The developmental plasticity of excitatory synapses is well established, particularly as a function of age. If similar principles apply to inhibitory synapses, then we would expect manipulations during juvenile development to produce a greater effect and experience-dependent changes to persist into adulthood. In this study, we first characterized the maturation of cortical inhibitory synapse function from just before the onset of hearing through adulthood. We then examined the long-term effects of developmental conductive hearing loss (CHL). Whole cell recordings from gerbil thalamocortical brain slices revealed a significant decrease in the decay time of inhibitory currents during the first 3 mo of normal development. When assessed in adults, developmental CHL led to an enduring decrease of inhibitory synaptic strength, whereas the maturation of synaptic decay time was only delayed. Early CHL also depressed the maximum discharge rate of fast-spiking, but not low-threshold spiking, inhibitory interneurons. We then asked whether adult onset CHL had a similar effect, but neither inhibitory current amplitude nor decay time was altered. Thus inhibitory synapse function displays a protracted development during which deficits can be induced by juvenile, but not adult, hearing loss. These long-lasting changes to inhibitory function may contribute to the auditory processing deficits associated with early hearing loss. PMID- 22090458 TI - Selectivity for three-dimensional contours and surfaces in the anterior intraparietal area. AB - The macaque anterior intraparietal area (AIP) is crucial for visually guided grasping. AIP neurons respond during the visual presentation of real-world objects and encode the depth profile of disparity-defined curved surfaces. We investigated the neural representation of curved surfaces in AIP using a stimulus reduction approach. The stimuli consisted of three-dimensional (3-D) shapes curved along the horizontal axis, the vertical axis, or both the horizontal and the vertical axes of the shape. The depth profile was defined solely by binocular disparity that varied along either the boundary or the surface of the shape or along both the boundary and the surface of the shape. The majority of AIP neurons were selective for curved boundaries along the horizontal or the vertical axis, and neural selectivity emerged at short latencies. Stimuli in which disparity varied only along the surface of the shape (with zero disparity on the boundaries) evoked selectivity in a smaller proportion of AIP neurons and at considerably longer latencies. AIP neurons were not selective for 3-D surfaces composed of anticorrelated disparities. Thus the neural selectivity for object depth profile in AIP is present when only the boundary is curved in depth, but not for disparity in anticorrelated stereograms. PMID- 22090459 TI - Extracellular pH dynamics of retinal horizontal cells examined using electrochemical and fluorometric methods. AB - Extracellular H(+) has been hypothesized to mediate feedback inhibition from horizontal cells onto vertebrate photoreceptors. According to this hypothesis, depolarization of horizontal cells should induce extracellular acidification adjacent to the cell membrane. Experiments testing this hypothesis have produced conflicting results. Studies examining carp and goldfish horizontal cells loaded with the pH-sensitive dye 5-hexadecanoylaminofluorescein (HAF) reported an extracellular acidification on depolarization by glutamate or potassium. However, investigations using H(+)-selective microelectrodes report an extracellular alkalinization on depolarization of skate and catfish horizontal cells. These studies differed in the species and extracellular pH buffer used and the presence or absence of cobalt. We used both techniques to examine H(+) changes from isolated catfish horizontal cells under identical experimental conditions (1 mM HEPES, no cobalt). HAF fluorescence indicated an acidification response to high extracellular potassium or glutamate. However, a clear extracellular alkalinization was found using H(+)-selective microelectrodes under the same conditions. Confocal microscopy revealed that HAF was not localized exclusively to the extracellular surface, but rather was detected throughout the intracellular compartment. A high degree of colocalization between HAF and the mitochondrion-specific dye MitoTracker was observed. When HAF fluorescence was monitored from optical sections from the center of a cell, glutamate produced an intracellular acidification. These results are consistent with a model in which depolarization allows calcium influx, followed by activation of a Ca(2+)/H(+) plasma membrane ATPase. Our results suggest that HAF is reporting intracellular pH changes and that depolarization of horizontal cells induces an extracellular alkalinization, which may relieve H(+)-mediated inhibition of photoreceptor synaptic transmission. PMID- 22090460 TI - Defensive peripersonal space: the blink reflex evoked by hand stimulation is increased when the hand is near the face. AB - Electrical stimulation of the median nerve at the wrist may elicit a blink reflex [hand blink reflex (HBR)] mediated by a neural circuit at brain stem level. As, in a Sherringtonian sense, the blink reflex is a defensive response, in a series of experiments we tested, in healthy volunteers, whether and how the HBR is modulated by the proximity of the stimulated hand to the face. Electromyographic activity was recorded from the orbicularis oculi, bilaterally. We observed that the HBR is enhanced when the stimulated hand is inside the peripersonal space of the face, compared with when it is outside, irrespective of whether the proximity of the hand to the face is manipulated by changing the position of the arm (experiment 1) or by rotating the head while keeping the arm position constant (experiment 3). Experiment 2 showed that such HBR enhancement has similar magnitude when the participants have their eyes closed. Experiments 4 and 5 showed, respectively, that the blink reflex elicited by the electrical stimulation of the supraorbital nerve, as well as the N20 wave of the somatosensory evoked potentials elicited by the median nerve stimulation, are entirely unaffected by hand position. Taken together, our results provide compelling evidence that the brain stem circuits mediating the HBR in humans undergo tonic and selective top-down modulation from higher order cortical areas responsible for encoding the location of somatosensory stimuli in external space coordinates. These findings support the existence of a "defensive" peripersonal space, representing a safety margin advantageous for survival. PMID- 22090461 TI - Origins of 1/f2 scaling in the power spectrum of intracortical local field potential. AB - It has been noted that the power spectrum of intracortical local field potential (LFP) often scales as 1/f(-2). It is thought that LFP mostly represents the spiking-related neuronal activity such as synaptic currents and spikes in the vicinity of the recording electrode, but no 1/f(2) scaling is detected in the spike power. Although tissue filtering or modulation of spiking activity by UP and DOWN states could account for the observed LFP scaling, there is no consensus as to how it arises. We addressed this question by recording simultaneously LFP and single neurons ("single units") from multiple sites in somatosensory cortex of anesthetized rats. Single-unit data revealed the presence of periods of high activity, presumably corresponding to the "UP" states when the neuronal membrane potential is depolarized, and periods of no activity, the putative "DOWN" states when the membrane potential is close to resting. As expected, the LFP power scaled as 1/f(2) but no such scaling was found in the power spectrum of spiking activity. Our analysis showed that 1/f(2) scaling in the LFP power spectrum was largely generated by the steplike transitions between UP and DOWN states. The shape of the LFP signal during these transitions, but not the transition timing, was crucial to obtain the observed scaling. These transitions were probably induced by synchronous changes in the membrane potential across neurons. We conclude that a 1/f(2) scaling in the LFP power indicates the presence of steplike transitions in the LFP trace and says little about the statistical properties of the associated neuronal firing. PMID- 22090462 TI - Characterization of thalamocortical responses of regular-spiking and fast-spiking neurons of the mouse auditory cortex in vitro and in silico. AB - We use a combination of in vitro whole cell recordings and computer simulations to characterize the cellular and synaptic properties that contribute to processing of auditory stimuli. Using a mouse thalamocortical slice preparation, we record the intrinsic membrane properties and synaptic properties of layer 3/4 regular-spiking (RS) pyramidal neurons and fast-spiking (FS) interneurons in primary auditory cortex (AI). We find that postsynaptic potentials (PSPs) evoked in FS cells are significantly larger and depress more than those evoked in RS cells after thalamic stimulation. We use these data to construct a simple computational model of the auditory thalamocortical circuit and find that the differences between FS and RS cells observed in vitro generate model behavior similar to that observed in vivo. We examine how feedforward inhibition and synaptic depression affect cortical responses to time-varying inputs that mimic sinusoidal amplitude-modulated tones. In the model, the balance of cortical inhibition and thalamic excitation evolves in a manner that depends on modulation frequency (MF) of the stimulus and determines cortical response tuning. PMID- 22090463 TI - A novel coding mechanism for social vocalizations in the lateral amygdala. AB - The amygdala plays a central role in evaluating the significance of acoustic signals and coordinating the appropriate behavioral responses. To understand how amygdalar responses modulate auditory processing and drive emotional expression, we assessed how neurons respond to and encode information that is carried within complex acoustic stimuli. We characterized responses of single neurons in the lateral nucleus of the amygdala to social vocalizations and synthetic acoustic stimuli in awake big brown bats. Neurons typically responded to most of the social vocalizations presented (mean = nine of 11 vocalizations) but differentially modulated both firing rate and response duration. Surprisingly, response duration provided substantially more information about vocalizations than did spike rate. In most neurons, variation in response duration depended, in part, on persistent excitatory discharge that extended beyond stimulus duration. Information in persistent firing duration was significantly greater than in spike rate, and the majority of neurons displayed more information in persistent firing, which was more likely to be observed in response to aggressive vocalizations (64%) than appeasement vocalizations (25%), suggesting that persistent firing may relate to the behavioral context of vocalizations. These findings suggest that the amygdala uses a novel coding strategy for discriminating among vocalizations and underscore the importance of persistent firing in the general functioning of the amygdala. PMID- 22090464 TI - Measurement of leg-length discrepancy using laser-based ultrasound method. AB - BACKGROUND: The evidence on the role of leg-length discrepancy (LLD) in low back pain (LBP) is contradictory, possibly due to the diversity of measurement methods. PURPOSE: To assess the reliability of a laser-based ultrasound method and its agreement with the radiographic method. MATERIAL AND METHODS: The measurement device consisted of a laser measure fixed to a rod holding the scanning head of the ultrasound and could be moved automatically by a linear actuator. The reliability of the measurement was evaluated using 20 healthy voluntary subjects with no known previous LLD (90% women, mean age 23 years). We assessed the agreement of the ultrasound method with a radiographic LLD measurement using 19 voluntary patients (95% men, mean age 38 years), who had had radiographic LLD measurements taken during the previous year. We used intraclass correlation co-efficients (ICC) and Bland & Altman analysis in the statistical analysis. RESULTS: The ICC value for agreement between methods was 0.97 (95% confidence intervals [CI] 0.93-0.99) indicating almost perfect agreement. The ICC values for both raters indicated almost perfect agreement between repeated measurements (ICC 0.996 and 0.994, respectively). In the Bland and Altman analysis, the mean difference was close to zero (0.56 mm and 0.40 mm), indicating minimal systematic error. CONCLUSION: The ultrasound-laser technique is quick and easy to perform. Both reliability and agreement with the radiographic method are excellent. The ultrasound measurement is non-invasive and therefore a potential alternative to radiographic methods in the evaluation of LLD. PMID- 22090465 TI - Metaplastic carcinoma of the breast: multimodality imaging and histopathologic assessment. AB - BACKGROUND: Metaplastic carcinomas are ductal carcinomas that display metaplastic transformation of the glandular epithelium to non-glandular mesenchymal tissue. Metaplastic carcinoma has a poorer prognosis than most other breast cancers, so the differential diagnosis is important. Although many clinical and pathologic findings have been reported, to our knowledge, few imaging findings related to metaplastic carcinoma have been reported. PURPOSE: To investigate whole-breast imaging findings, including mammography, sonography, MRI, and pathologic findings, including immunohistochemical studies of metaplastic carcinomas of the breast. MATERIAL AND METHODS: We analyzed 33 cases of metaplastic carcinoma between January 2001 and January 2011. Mammography, ultrasonography, and MRI were recorded retrospectively using the American College of Radiology (ACR) breast imaging reporting and data system (BI-RADS) lexicon. Immunohistochemical studies of estrogen receptor (ER), progesterone receptor (PR), p53, and C-erbB-2 were performed. RESULTS: The most common mammographic findings were oval shape (37%), circumscribed margin (59%), and high density (74%). The most common sonographic findings were irregular shape (59.4%), microlobulated margin (41%), complex echogenicity (81%), parallel orientation (97%), and posterior acoustic enhancement (50%). Axillary lymph node metastases were noted for 25% of the sonographic examinations. On MRI, the most common findings of margin and shape were irregularity (57% and 52.4%, respectively). High signal intensity was the most common finding on T2-weighted images (57%). Immunohistochemical profile was negative for ER (91%, 29/32) and PR (81%, 26/32). CONCLUSION: Metaplastic carcinomas might display more benign features and less axillary lymph node metastasis than IDC. High signal intensity on T2 MRI images and hormone receptor negativity would be helpful in differentiating this tumor from other breast cancers. PMID- 22090466 TI - Compression stockings with moderate pressure are able to reduce chronic leg oedema. AB - AIM: To compare the efficacy of compression stockings and inelastic, high pressure bandages concerning leg volume reduction in patients with chronic leg oedema. MATERIAL AND METHODS: Forty-two legs of 30 patients with chronic leg oedema caused by venous stasis were randomized to receive a strong inelastic bandage (IB) or an elastic stocking (ES) exerting a pressure of 23-32 mmHg. Changes in leg oedema were assessed after two and seven days by water displacement volumetry, measurements of leg circumferences and of skin thickness by using Duplex ultrasound. Interface pressure was registered under the compression devices for seven days. RESULTS: There was no significant difference between stockings and bandages, which both produced a significant reduction in leg volume after two days (-9.6% [95% CI 7.5-11.8] by ES and -11.5% [95% CI 9.9 13.2%] by IB) and after seven days (-13.2% [95% CI 10.4-16.2] by ES and -15.6% [95% CI 12.8-18.4] by IB). Bandages showed a more pronounced reduction in leg circumference and in skin thickness in the calf region. The pressure of IB in the lying position fell from initially 63 to 22 mmHg after two days, but only from 33 to 26 mmHg under ES (median values). The optimal pressure range concerning oedema reduction was found between 40 and 60 mmHg, while higher pressures produced by bandages showed a negative correlation with volume reduction. CONCLUSIONS: Compression stockings exerting a pressure of around 30 mmHg are nearly as effective as high-pressure bandages with an initial pressure over 60 mmHg in reducing chronic leg oedema. PMID- 22090467 TI - A dietary pattern including nopal, chia seed, soy protein, and oat reduces serum triglycerides and glucose intolerance in patients with metabolic syndrome. AB - Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered. PMID- 22090468 TI - Total and specific polyphenol intakes in midlife are associated with cognitive function measured 13 years later. AB - Polyphenols, and in particular flavonoids, are omnipresent plant-food components displaying biochemical properties possibly beneficial to brain health. We sought to evaluate the long-term association between total and class-specific polyphenol intake and cognitive performance. Polyphenol intake was estimated using the Phenol-Explorer database applied to at least six 24-h dietary records collected in 1994-1996 as part of the SU.VI.MAX (Supplementation en Vitamines et Mineraux Antioxydants) study. The cognitive performance of 2574 middle-aged adults participating in the cohort was assessed in 2007-2009 using the following four neuropsychological tests: phonemic and semantic fluency, the RI-48 Cued Recall test, the Trail Making test, and Forward and Backward Digit Span. Inter correlations among the test scores were estimated with principal component analysis. Associations between polyphenol intake and cognition were assessed by multivariate linear regression and ANCOVA. In multivariate models, high total polyphenol intake was associated with better language and verbal memory (P = 0.01) but not with executive functioning (P = 0.09). More specifically, intake of catechins (P = 0.001), theaflavins (P = 0.002), flavonols (P = 0.01), and hydroxybenzoic acids (P = 0.0004) was positively associated with language and verbal memory, especially with episodic memory assessed by the RI-48 test. In contrast, negative associations between scores on executive functioning and intake of dihydrochalcones (P = 0.01), catechins (P = 0.01), proanthocyanidins (P = 0.01), and flavonols (P = 0.01) were detected. High intake of specific polyphenols, including flavonoids and phenolic acids, may help to preserve verbal memory, which is a salient vulnerable domain in pathological brain aging. Further investigations are needed to clarify the observed negative associations regarding executive functioning. PMID- 22090469 TI - Glycemic index predicts individual glucose responses after self-selected breakfasts in free-living, abdominally obese adults. AB - The degree to which an individual's glycemic response to a meal is determined by the glycemic index (GI) and other components of the meal remains unclear, especially when meals are not consumed in a highly controlled research setting. To address this question, we analyzed data collected during the run-in period of a clinical trial. Free-living, nondiabetic adults (n = 57) aged 53.9 +/- 9.8 y (mean +/- SD) with a BMI of 33.9 +/- 5.3 kg/m(2) and waist circumference of 109 +/- 11 cm underwent a 75-g oral glucose tolerance test (OGTT) and, on a separate day, wore a continuous glucose-monitoring system (CGMS) for 24 h during which time they recorded all foods consumed. The protein, fat, and available carbohydrate (avCHO) content and GI of the breakfast meals were calculated from the food records and the incremental areas under the glycemic response curves (iAUC) for 2 h after breakfast (iAUC(breakfast)) were calculated from CGMS data. Values for iAUC(breakfast), avCHO, fat, fiber, and BMI were normalized by log transformation. The ability of participant characteristics and breakfast composition to predict individual iAUC(breakfast) responses was determined using step-wise multiple linear regression. A total of 56% of the variation in iAUC(breakfast) was explained by GI (30%; P < 0.001), iAUC after the OGTT (11%; P < 0.001), avCHO (11%; P < 0.001), and waist circumference (3%; P = 0.049); the effects of fat, protein, dietary fiber, age, sex, and BMI were not significant. We concluded that, in free-living, abdominally obese adults, GI is a significant determinant of individual glycemic responses elicited by self-selected breakfast meals. In this study, GI was a more important determinant of glycemic response than carbohydrate intake. PMID- 22090470 TI - Use of laboratory studies for the design, explanation, and validation of human micronutrient intervention studies. AB - Many micronutrient supplementation trials have led to important new findings relevant to public health, but some outcomes have been unclear or concerning. Can and should laboratory studies and animal models be used more extensively to pretest the proposed designs of human studies? This paper illustrates, as examples, the contributions that animal models have made to several major advances in understanding the biology of the micronutrients vitamin A and carotenoids, and it proposes that animal studies can play a more integrated role in public health nutrition by serving as a first line of interrogation for study designs and thereby as a means of refining the designs of human studies so that large, expensive, and logistically difficult human trials will yield the best possible information. PMID- 22090471 TI - International Union of Basic and Clinical Pharmacology. LXXXV: calcium-activated chloride channels. AB - Calcium-activated chloride channels (CaCCs) are widely expressed in various tissues and implicated in physiological processes such as sensory transduction, epithelial secretion, and smooth muscle contraction. Transmembrane proteins with unknown function 16 (TMEM16A) has recently been identified as a major component of CaCCs. Detailed molecular analysis of TMEM16A will be needed to understand its structure-function relationships. The role this channel plays in physiological systems remains to be established and is currently a subject of intense investigation. PMID- 22090472 TI - Therapeutic implications for striatal-enriched protein tyrosine phosphatase (STEP) in neuropsychiatric disorders. AB - Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase that modulates key signaling molecules involved in synaptic plasticity and neuronal function. Targets include extracellular-regulated kinase 1 and 2 (ERK1/2), stress-activated protein kinase p38 (p38), the Src family tyrosine kinase Fyn, N-methyl-D-aspartate receptors (NMDARs), and alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). STEP-mediated dephosphorylation of ERK1/2, p38, and Fyn leads to inactivation of these enzymes, whereas STEP-mediated dephosphorylation of surface NMDARs and AMPARs promotes their endocytosis. Accordingly, the current model of STEP function posits that it opposes long-term potentiation and promotes long-term depression. Phosphorylation, cleavage, dimerization, ubiquitination, and local translation all converge to maintain an appropriate balance of STEP in the central nervous system. Accumulating evidence over the past decade indicates that STEP dysregulation contributes to the pathophysiology of several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, fragile X syndrome, epileptogenesis, alcohol-induced memory loss, Huntington's disease, drug abuse, stroke/ischemia, and inflammatory pain. This comprehensive review discusses STEP expression and regulation and highlights how disrupted STEP function contributes to the pathophysiology of diverse neuropsychiatric disorders. PMID- 22090474 TI - Arylamine N-acetyltransferase 1: a novel drug target in cancer development. AB - The human arylamine N-acetyltransferases first attracted attention because of their role in drug metabolism. However, much of the current literature has focused on their role in the activation and detoxification of environmental carcinogens and how genetic polymorphisms in the genes create predispositions to increased or decreased cancer risk. There are two closely related genes on chromosome 8 that encode the two human arylamine N-acetyltransferases--NAT1 and NAT2. Although NAT2 has restricted tissue expression, NAT1 is found in almost all tissues of the body. There are several single-nucleotide polymorphisms in the protein coding and 3'-untranslated regions of the gene that affect enzyme activity. However, NAT1 is also regulated by post-translational and environmental factors, which may be of greater importance than genotype in determining tissue NAT1 activities. Recent studies have suggested a novel role for this enzyme in cancer cell growth. NAT1 is up-regulated in several cancer types, and overexpression can lead to increased survival and resistance to chemotherapy. Although a link to folate homeostasis has been suggested, many of the effects attributed to NAT1 and cancer cell growth remain to be explained. Nevertheless, the enzyme has emerged as a viable candidate for drug development, which should lead to small molecule inhibitors for preclinical and clinical evaluation. PMID- 22090473 TI - Genome-environment interactions that modulate aging: powerful targets for drug discovery. AB - Aging is the major biomedical challenge of this century. The percentage of elderly people, and consequently the incidence of age-related diseases such as heart disease, cancer, and neurodegenerative diseases, is projected to increase considerably in the coming decades. Findings from model organisms have revealed that aging is a surprisingly plastic process that can be manipulated by both genetic and environmental factors. Here we review a broad range of findings in model organisms, from environmental to genetic manipulations of aging, with a focus on those with underlying gene-environment interactions with potential for drug discovery and development. One well-studied dietary manipulation of aging is caloric restriction, which consists of restricting the food intake of organisms without triggering malnutrition and has been shown to retard aging in model organisms. Caloric restriction is already being used as a paradigm for developing compounds that mimic its life-extension effects and might therefore have therapeutic value. The potential for further advances in this field is immense; hundreds of genes in several pathways have recently emerged as regulators of aging and caloric restriction in model organisms. Some of these genes, such as IGF1R and FOXO3, have also been associated with human longevity in genetic association studies. The parallel emergence of network approaches offers prospects to develop multitarget drugs and combinatorial therapies. Understanding how the environment modulates aging-related genes may lead to human applications and disease therapies through diet, lifestyle, or pharmacological interventions. Unlocking the capacity to manipulate human aging would result in unprecedented health benefits. PMID- 22090475 TI - Decoding action intentions in parietofrontal circuits. PMID- 22090476 TI - Synaptic properties of corticocortical connections between the primary and secondary visual cortical areas in the mouse. AB - Despite the importance of corticocortical connections, few published studies have investigated the functional, synaptic properties of such connections in any species, because most studies have been purely anatomical or aimed at functional features other than synaptic properties. We recently published a study of synaptic properties of connections between the primary and secondary cortical auditory areas in brain slices from the mouse, and, in the present study, we aimed to extend this by performing analogous studies of the primary and secondary visual areas (V1 and V2). We found effectively the same results. That is, connections between V1 and V2 in both directions were quite similar; in each case, the glutamatergic inputs could be classified as one of two types, Class 1B (formerly "driver") and Class 2 (formerly "modulator"). There is a clear laminar correlation for these different inputs, in terms of both the laminae of origin and those in which the recorded cells were located. Our data suggest a common pattern to the functional organization of corticocortical connectivity in the mouse cortex. PMID- 22090477 TI - Robust central reduction of amyloid-beta in humans with an orally available, non peptidic beta-secretase inhibitor. AB - According to the amyloid cascade hypothesis, cerebral deposition of amyloid-beta peptide (Abeta) is critical for Alzheimer's disease (AD) pathogenesis. Abeta generation is initiated when beta-secretase (BACE1) cleaves the amyloid precursor protein. For more than a decade, BACE1 has been a prime target for designing drugs to prevent or treat AD. However, development of such agents has turned out to be extremely challenging, with major hurdles in cell penetration, oral bioavailability/metabolic clearance, and brain access. Using a fragment-based chemistry strategy, we have generated LY2811376 [(S)-4-(2,4-difluoro-5-pyrimidin 5-yl-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]thiazin-2-ylamine], the first orally available non-peptidic BACE1 inhibitor that produces profound Abeta-lowering effects in animals. The biomarker changes obtained in preclinical animal models translate into man at doses of LY2811376 that were safe and well tolerated in healthy volunteers. Prominent and long-lasting Abeta reductions in lumbar CSF were measured after oral dosing of 30 or 90 mg of LY2811376. This represents the first translation of BACE1-driven biomarker changes in CNS from preclinical animal models to man. Because of toxicology findings identified in longer-term preclinical studies, this compound is no longer progressing in clinical development. However, BACE1 remains a viable target because the adverse effects reported here were recapitulated in LY2811376-treated BACE1 KO mice and thus are unrelated to BACE1 inhibition. The magnitude and duration of central Abeta reduction obtainable with BACE1 inhibition positions this protease as a tractable small-molecule target through which to test the amyloid hypothesis in man. PMID- 22090478 TI - Disrupting effect of drug-induced reward on spatial but not cue-guided learning: implication of the striatal protein kinase A/cAMP response element-binding protein pathway. AB - The multiple memory systems hypothesis posits that different neural circuits function in parallel and may compete for information processing and storage. For example, instrumental conditioning would depend on the striatum, whereas spatial memory may be mediated by a circuit centered on the hippocampus. However, the nature of the task itself is not sufficient to select durably one system over the other. In this study, we investigated the effects of natural and pharmacological rewards on the selection of a particular memory system during learning. We compared the effects of food- or drug-induced activation of the reward system on cue-guided versus spatial learning using a Y-maze discrimination task. Drug induced reward severely impaired the acquisition of a spatial discrimination task but spared the cued version of the task. Immunohistochemical analysis of the phosphorylated form of the cAMP response element binding (CREB) protein and c-Fos expression induced by behavioral testing revealed that the spatial deficit was associated with a decrease of both markers within the hippocampus and the prefrontal cortex. In contrast, drug reward potentiated the cued learning-induced CREB phosphorylation within the dorsal striatum. Administration of the protein kinase A inhibitor 8-Bromo-adenosine-3',5'-cyclic monophosphorothioate Rp isomer (Rp-cAMPS) into the dorsal striatum before training completely reversed the drug induced spatial deficit and restored CREB phosphorylation levels within the hippocampus and the prefrontal cortex. Therefore, drug-induced striatal hyperactivity may underlie the declarative memory deficit reported here. This mechanism could represent an important early step toward the development of addictive behaviors by promoting conditioning to the detriment of more flexible forms of memory. PMID- 22090479 TI - Selectivity for spectral motion as a neural computation for encoding natural communication signals in bat inferior colliculus. AB - This study examines the neural computations performed by neurons in the auditory system to be selective for the direction and velocity of signals sweeping upward or downward in frequency, termed spectral motion. We show that neurons in the auditory midbrain of Mexican free-tailed bats encode multiple spectrotemporal features of natural communication sounds. These features to which each neuron is tuned are nonlinearly combined to produce selectivity for spectral motion cues present in their conspecific calls, such as direction and velocity. We find that the neural computations resulting in selectivity for spectral motion are analogous to models of motion selectivity studied in vision. Our analysis revealed that auditory neurons in the inferior colliculus (IC) are avoiding spectrotemporal modulations that are redundant across different bat communication signals and are specifically tuned for modulations that distinguish each call from another by their frequency-modulated direction and velocity, suggesting that spectral motion is the neural computation through which IC neurons are encoding specific features of conspecific vocalizations. PMID- 22090480 TI - Critical roles of transitional cells and Na/K-ATPase in the formation of vestibular endolymph. AB - The mechanotransduction of vestibular sensory cells depends on the high endolymphatic potassium concentration ([K+]) maintained by a fine balance between K+ secretion and absorption by epithelial cells. Despite the crucial role of endolymph as an electrochemical motor for mechanotransduction, little is known about the processes that govern endolymph formation. To address these, we took advantage of an organotypic rodent model, which regenerates a genuine neonatal vestibular endolymphatic compartment, facilitating the determination of endolymphatic [K+] and transepithelial potential (Vt) during endolymph formation. While mature Vt levels are almost immediately achieved, K+ accumulates to reach a steady [K+] by day 5 in culture. Inhibition of sensory cell K+ efflux enhances [K+] regardless of the blocker used (FM1.43, amikacin, gentamicin, or gadolinium). Targeting K+ secretion with bumetanide partially and transiently reduces [K+], while ouabain application and Kcne1 deletion almost abolishes it. Immunofluorescence studies demonstrate that dark cells do not express Na-K-2Cl cotransporter 1 (the target of bumetanide) in cultured and young mouse utricles, while Na/K-ATPase (the target of ouabain) is found in dark cells and transitional cells. This global analysis of the involvement of endolymphatic homeostasis actors in the immature organ (1) confirms that KCNE1 channels are necessary for K+ secretion, (2) highlights Na/K-ATPase as the key endolymphatic K+ provider and shows that Na-K-2Cl cotransporter 1 has a limited impact on K+ influx, and (3) demonstrates that transitional cells are involved in K+ secretion in the early endolymphatic compartment. PMID- 22090481 TI - NMDA receptor agonists fail to alter release from cerebellar basket cells. AB - Previous studies of NMDA receptor (NMDAR) expression on axons of cerebellar molecular layer interneurons have produced conflicting results. We made use of the calcium sensitivity of vesicular release machinery to test for NMDAR activity in basket cell axons. Iontophoresis of l-aspartate, an NMDAR agonist, onto basket cell axon collaterals had no effect on evoked IPSCs measured in synaptically coupled Purkinje cells. Furthermore, calcium indicators in basket cell varicosities did not report any change in intracellular calcium following iontophoresis of l-aspartate or two-photon uncaging of glutamate. In contrast, activation of presynaptic purinergic receptors by iontophoresis of ATP decreased evoked IPSC amplitudes and action potential-evoked calcium transients in axonal varicosities, demonstrating the effectiveness of activating presynaptic receptors by iontophoresis. We find no evidence for functional NMDARs in basket cell varicosities. PMID- 22090482 TI - Regionally specific human GABA concentration correlates with tactile discrimination thresholds. AB - The neural mechanisms underlying variability in human sensory perception remain incompletely understood. In particular, few studies have attempted to investigate the relationship between in vivo measurements of neurochemistry and individuals' behavioral performance. Our previous work found a relationship between GABA concentration in the visual cortex and orientation discrimination thresholds (Edden et al., 2009). In the present study, we used magnetic resonance spectroscopy of GABA and psychophysical testing of vibrotactile frequency thresholds to investigate whether individual differences in tactile frequency discrimination performance are correlated with GABA concentration in sensorimotor cortex. Behaviorally, individuals showed a wide range of discrimination thresholds ranging from 3 to 7.6 Hz around the 25 Hz standard. These frequency discrimination thresholds were significantly correlated with GABA concentration (r = -0.58; p < 0.05) in individuals' sensorimotor cortex, but not with GABA concentration in an occipital control region (r = -0.04). These results demonstrate a link between GABA concentration and frequency discrimination in vivo, and support the hypothesis that GABAergic mechanisms have an important role to play in sensory discrimination. PMID- 22090483 TI - Representation of perceptually invisible image motion in extrastriate visual area MT of macaque monkeys. AB - Why does the world appear stable despite the visual motion induced by eye movements during fixation? We find that the answer must reside in how visual motion signals are interpreted by perception, because MT neurons in monkeys respond to the image motion caused by eye drifts in the presence of a stationary stimulus. Several features suggest a visual origin for the responses of MT neurons during fixation: spike-triggered averaging yields a peak image velocity in the preferred direction that precedes spikes by ~60 ms; image velocity during fixation and firing rate show similar peaks in power at 4-5 Hz; and average MT firing during a period of fixation is related monotonically to the image speed along the preferred axis of the neurons 60 ms earlier. The percept caused by the responses of MT neurons during fixation depends on the distribution of activity across the population of neurons of different preferred speeds. For imposed stimulus motion, the population response peaks for neurons that prefer the actual target speed. For small image motions caused by eye drifts during fixation, the population response is large, but is noisy and does not show a clear peak. This representation of image motion in MT would be ignored if perception interprets the population response in the context of a prior of zero speed. Then, we would see a stable scene despite MT responses caused by eye drifts during fixation. PMID- 22090484 TI - A wide diversity of cortical GABAergic interneurons derives from the embryonic preoptic area. AB - GABA-containing (GABAergic) interneurons comprise a very heterogeneous group of cells that are crucial for cortical function. Different classes of interneurons specialize in targeting specific subcellular domains of excitatory pyramidal cells or other interneurons, which provides cortical circuits with an enormous capability for information processing. As in other regions of the CNS, cortical interneuron diversity is thought to emerge from the genetic specification of different groups of progenitor cells within the subpallium. Most cortical interneurons originate from two main regions, the medial and the caudal ganglionic eminences (MGE and CGE, respectively). In addition, it has been shown that progenitors in the embryonic preoptic area (POA) also produce a small population of cortical GABAergic interneurons. Here, we show that the contribution of the POA to the complement of cortical GABAergic interneurons is larger than previously believed. Using genetic fate mapping and in utero transplantation experiments, we demonstrate that Dbx1-expressing progenitor cells in the POA give rise to a small but highly diverse cohort of cortical interneurons, with some neurochemical and electrophysiological characteristics that were previously attributed to MGE- or CGE-derived interneurons. There are, however, some features that seem to distinguish POA-derived interneurons from MGE or CGE-derived cells, such as their preferential laminar location. These results indicate that the mechanisms controlling the specification of different classes of cortical interneurons might be more complex than previously expected. Together with earlier findings, our results also suggest that the POA generates nearly 10% of the GABAergic interneurons in the cerebral cortex of the mouse. PMID- 22090485 TI - beta-III spectrin is critical for development of purkinje cell dendritic tree and spine morphogenesis. AB - Mutations in the gene encoding beta-III spectrin give rise to spinocerebellar ataxia type 5, a neurodegenerative disease characterized by progressive thinning of the molecular layer, loss of Purkinje cells and increasing motor deficits. A mouse lacking full-length beta-III spectrin (beta-III-/-) displays a similar phenotype. In vitro and in vivo analyses of Purkinje cells lacking beta-III spectrin, reveal a critical role for beta-III spectrin in Purkinje cell morphological development. Disruption of the normally well ordered dendritic arborization occurs in Purkinje cells from beta-III-/- mice, specifically showing a loss of monoplanar organization, smaller average dendritic diameter and reduced densities of Purkinje cell spines and synapses. Early morphological defects appear to affect distribution of dendritic, but not axonal, proteins. This study confirms that thinning of the molecular layer associated with disease pathogenesis is a consequence of Purkinje cell dendritic degeneration, as Purkinje cells from 8-month-old beta-III-/- mice have drastically reduced dendritic volumes, surface areas and total dendritic lengths compared with 5- to 6-week-old beta-III-/- mice. These findings highlight a critical role of beta-III spectrin in dendritic biology and are consistent with an early developmental defect in beta-III-/- mice, with abnormal Purkinje cell dendritic morphology potentially underlying disease pathogenesis. PMID- 22090486 TI - State-dependent, bidirectional modulation of neural network activity by endocannabinoids. AB - The endocannabinoid (eCB) system and the cannabinoid CB1 receptor (CB1R) play key roles in the modulation of brain functions. Although actions of eCBs and CB1Rs are well described at the synaptic level, little is known of their modulation of neural activity at the network level. Using microelectrode arrays, we have examined the role of CB1R activation in the modulation of the electrical activity of rat and mice cortical neural networks in vitro. We find that exogenous activation of CB1Rs expressed on glutamatergic neurons decreases the spontaneous activity of cortical neural networks. Moreover, we observe that the net effect of the CB1R antagonist AM251 inversely correlates with the initial level of activity in the network: blocking CB1Rs increases network activity when basal network activity is low, whereas it depresses spontaneous activity when its initial level is high. Our results reveal a complex role of CB1Rs in shaping spontaneous network activity, and suggest that the outcome of endogenous neuromodulation on network function might be state dependent. PMID- 22090487 TI - Amping up effort: effects of d-amphetamine on human effort-based decision-making. AB - Animal studies suggest the neurotransmitter dopamine (DA) plays an important role in decision-making. In rats, DA depletion decreases tolerance for effort and probability costs, while drugs enhancing DA increase tolerance for these costs. However, data regarding the effect of DA manipulations on effort and probability costs in humans remain scarce. The current study examined acute effects of d amphetamine, an indirect DA agonist, on willingness of healthy human volunteers to exert effort for monetary rewards at varying levels of reward value and reward probability. Based on preclinical research, we predicted amphetamine would increase exertion of effort, particularly when reward probability was low. Over three sessions, 17 healthy normal adults received placebo, d-amphetamine 10 mg, and 20 mg under counterbalanced double-blind conditions and completed the Effort Expenditure for Rewards Task. Consistent with predictions, amphetamine enhanced willingness to exert effort, particularly when reward probability was lower. Amphetamine did not alter effects of reward magnitude on willingness to exert effort. Amphetamine sped task performance, but its psychomotor effects were not strongly related to its effects on decision-making. This is the first demonstration in humans that dopaminergic manipulations alter willingness to exert effort for rewards. These findings help elucidate neurochemical substrates of choice, with implications for neuropsychiatric diseases characterized by dopaminergic dysfunction and motivational deficits. PMID- 22090488 TI - A seven-transmembrane receptor that mediates avoidance response to dihydrocaffeic acid, a water-soluble repellent in Caenorhabditis elegans. AB - The ability to detect harmful chemicals rapidly is essential for the survival of all animals. In Caenorhabditis elegans (C. elegans), repellents trigger an avoidance response, causing animals to move away from repellents. Dihydrocaffeic acid (DHCA) is a water-soluble repellent and nonflavonoid catecholic compound that can be found in plant products. Using a Xenopus laevis (X. laevis) oocyte expression system, we identified a candidate dihydrocaffeic acid receptor (DCAR), DCAR-1. DCAR-1 is a novel seven-transmembrane protein that is expressed in the ASH avoidance sensory neurons of C. elegans. dcar-1 mutant animals are defective in avoidance response to DHCA, and cell-specific expression of dcar-1 in the ASH neurons of dcar-1 mutant animals rescued the defect in avoidance response to DHCA. Our findings identify DCAR-1 as the first seven-transmembrane receptor required for avoidance of a water-soluble repellent, DHCA, in C. elegans. PMID- 22090489 TI - The sound of consciousness: neural underpinnings of auditory perception. AB - The neural correlates of consciousness (NCC), i.e., patterns of brain activity that specifically accompany a particular conscious experience, have been investigated mainly in the visual system using particularly suited paradigms, such as binocular rivalry and multistable percepts in combination with neural recordings or neuroimaging. Through the same principles, we look here for possible NCC in the auditory modality exploiting the properties of the Deutsch's illusion, a stimulation condition in which a sequence of two specular dichotic stimuli presented in alternation causes an illusory segregation of pitch and side (ear of origin), which can yield up to four different auditory percepts per dichotic stimulus. Using magnetoencephalography in humans, we observed cortical activity specifically accompanying conscious experience of pitch inside an early bilateral network, including the Heschl's gyrus, the middle temporal gyrus, the right inferior, and the superior frontal gyri. The conscious experience of perceived side was instead accompanied by later activity observed bilaterally in the inferior parietal lobe and in the superior frontal gyrus. These results suggest that the NCC are not independent of stimulus features and modality and that, even at the higher cortical levels, the different aspects of a single perceptual scene may not be simultaneously processed. PMID- 22090490 TI - Epigenetic regulation of motor neuron cell death through DNA methylation. AB - DNA methylation is an epigenetic mechanism for gene silencing engaged by DNA methyltransferase (Dnmt)-catalyzed methyl group transfer to cytosine residues in gene-regulatory regions. It is unknown whether aberrant DNA methylation can cause neurodegeneration. We tested the hypothesis that Dnmts can mediate neuronal cell death. Enforced expression of Dnmt3a induced degeneration of cultured NSC34 cells. During apoptosis of NSC34 cells induced by camptothecin, levels of Dnmt1 and Dnmt3a increased fivefold and twofold, respectively, and 5-methylcytosine accumulated in nuclei. Truncation mutation of the Dnmt3a catalytic domain and Dnmt3a RNAi blocked apoptosis of cultured neurons. Inhibition of Dnmt catalytic activity with RG108 and procainamide protected cultured neurons from excessive DNA methylation and apoptosis. In vivo, Dnmt1 and Dnmt3a are expressed differentially during mouse brain and spinal cord maturation and in adulthood when Dnmt3a is abundant in synapses and mitochondria. Dnmt1 and Dnmt3a are expressed in motor neurons of adult mouse spinal cord, and, during their apoptosis induced by sciatic nerve avulsion, nuclear and cytoplasmic 5 methylcytosine immunoreactivity, Dnmt3a protein levels and Dnmt enzyme activity increased preapoptotically. Inhibition of Dnmts with RG108 blocked completely the increase in 5-methycytosine and the apoptosis of motor neurons in mice. In human amyotrophic lateral sclerosis (ALS), motor neurons showed changes in Dnmt1, Dnmt3a, and 5-methylcytosine similar to experimental models. Thus, motor neurons can engage epigenetic mechanisms to drive apoptosis, involving Dnmt upregulation and increased DNA methylation. These cellular mechanisms could be relevant to human ALS pathobiology and disease treatment. PMID- 22090491 TI - Sharp Ca2+ nanodomains beneath the ribbon promote highly synchronous multivesicular release at hair cell synapses. AB - Hair cell ribbon synapses exhibit several distinguishing features. Structurally, a dense body, or ribbon, is anchored to the presynaptic membrane and tethers synaptic vesicles; functionally, neurotransmitter release is dominated by large EPSC events produced by seemingly synchronous multivesicular release. However, the specific role of the synaptic ribbon in promoting this form of release remains elusive. Using complete ultrastructural reconstructions and capacitance measurements of bullfrog amphibian papilla hair cells dialyzed with high concentrations of a slow Ca2+ buffer (10 mM EGTA), we found that the number of synaptic vesicles at the base of the ribbon correlated closely to those vesicles that released most rapidly and efficiently, while the rest of the ribbon-tethered vesicles correlated to a second, slower pool of vesicles. Combined with the persistence of multivesicular release in extreme Ca2+ buffering conditions (10 mM BAPTA), our data argue against the Ca2+-dependent compound fusion of ribbon tethered vesicles at hair cell synapses. Moreover, during hair cell depolarization, our results suggest that elevated Ca2+ levels enhance vesicle pool replenishment rates. Finally, using Ca2+ diffusion simulations, we propose that the ribbon and its vesicles define a small cytoplasmic volume where Ca2+ buffer is saturated, despite 10 mM BAPTA conditions. This local buffer saturation permits fast and large Ca2+ rises near release sites beneath the synaptic ribbon that can trigger multiquantal EPSCs. We conclude that, by restricting the available presynaptic volume, the ribbon may be creating conditions for the synchronous release of a small cohort of docked vesicles. PMID- 22090492 TI - Serum response factor is required for cortical axon growth but is dispensable for neurogenesis and neocortical lamination. AB - Previous studies have shown that neuron-specific deletion of serum response factor (SRF) results in deficits in tangential cell migration, guidance-dependent circuit assembly, activity-dependent gene expression, and synaptic plasticity in the hippocampus. Furthermore, SRF deletion in mouse embryonic stem cells causes cell death in vitro. However, the requirement of SRF for early neuronal development including neural stem cell homeostasis, neurogenesis, and axonal innervations remains unknown. Here, we report that SRF is critical for development of major axonal tracts in the forebrain. Conditional mutant mice lacking SRF in neural progenitor cells (Srf-Nestin-cKO) exhibit striking deficits in cortical axonal projections including corticostriatal, corticospinal, and corticothalamic tracts, and they show a variable loss of the corpus callosum. Neurogenesis and interneuron specification occur normally in the absence of SRF and the deficits in axonal projections were not due to a decrease or loss in cell numbers. Radial migration of neurons and neocortical lamination were also not affected. No aberrant cell death was observed during development, whereas there was an increase in the number of proliferative cells in the ventricular zone from embryonic day 14 to day 18. Similar axonal tract deficits were also observed in mutant mice lacking SRF in the developing excitatory neurons of neocortex and hippocampus (Srf-NEX-cKO). Together, these findings suggest distinct roles for SRF during neuronal development; SRF is specifically required in a cell autonomous manner for axonal tract development but is dispensable for cell survival, neurogenesis, neocortical lamination, and neuronal differentiation. PMID- 22090493 TI - Diverse precerebellar neurons share similar intrinsic excitability. AB - The cerebellum dedicates a majority of the brain's neurons to processing a wide range of sensory, motor, and cognitive signals. Stereotyped circuitry within the cerebellar cortex suggests that similar computations are performed throughout the cerebellum, but little is known about whether diverse precerebellar neurons are specialized for the nature of the information they convey. In vivo recordings indicate that firing responses to sensory or motor stimuli vary dramatically across different precerebellar nuclei, but whether this reflects diverse synaptic inputs or differentially tuned intrinsic excitability has not been determined. We targeted whole-cell patch-clamp recordings to neurons in eight precerebellar nuclei which were retrogradely labeled from different regions of the cerebellum in mice. Intrinsic physiology was compared across neurons in the medial vestibular, external cuneate, lateral reticular, prepositus hypoglossi, supragenual, Roller/intercalatus, reticularis tegmenti pontis, and pontine nuclei. Within the firing domain, precerebellar neurons were remarkably similar. Firing faithfully followed temporally modulated inputs, could be sustained at high rates, and was a linear function of input current over a wide range of inputs and firing rates. Pharmacological analyses revealed common expression of Kv3 currents, which were essential for a wide linear firing range, and of SK (small-conductance calcium-activated potassium) currents, which were essential for a wide linear input range. In contrast, membrane properties below spike threshold varied considerably within and across precerebellar nuclei, as evidenced by variability in postinhibitory rebound firing. Our findings indicate that diverse precerebellar neurons perform similar scaling computations on their inputs but may be differentially tuned to synaptic inhibition. PMID- 22090494 TI - Elimination of redundant synaptic inputs in the absence of synaptic strengthening. AB - Synaptic refinement, a developmental process that consists of selective elimination and strengthening of immature synapses, is essential for the formation of precise neuronal circuits and proper brain function. At glutamatergic synapses in the brain, activity-dependent recruitment of AMPA receptors (AMPARs) is a key mechanism underlying the strengthening of immature synapses. Studies using receptor overexpression have shown that the recruitment of AMPARs is subunit specific. With the notable exception of hippocampal CA3-CA1 synapses, however, little is known about how native receptors behave or the roles of specific AMPAR subunits in synaptic refinement in vivo. Using patch-clamp recordings in acute slices, we examined developmental refinement of whisker relay (lemniscal) synapses in the thalamus in mice deficient of AMPAR subunits. Deletion of GluA3 or GluA4 caused significant reductions of synaptic AMPAR currents in thalamic neurons at P16-P17, with a greater reduction observed in GluA3-deficient mice. Deletions of both GluA3 and GluA4 abolished synaptic AMPAR responses in the majority of thalamic neurons, indicating that at thalamic relay synapses AMPARs are composed primarily of GluA3 and GluA4. Surprisingly, deletions of GluA3 or GluA4 or both had no effect on the elimination of relay inputs: the majority of thalamic neurons in these knock-out mice-as in wild-type mice-receive a single relay input. However, experience-dependent strengthening of thalamic relay synapses was impaired in GluA3 knock-out mice. Together these findings suggest that the elimination of immature glutamatergic synapses proceeds normally in the absence of synaptic strengthening, and highlight the role of GluA3-containing AMPARs in experience-dependent synaptic plasticity. PMID- 22090496 TI - One action system or two? Evidence for common central preparatory mechanisms in voluntary and stimulus-driven actions. AB - Human behavior is comprised of an interaction between intentionally driven actions and reactions to changes in the environment. Existing data are equivocal concerning the question of whether these two action systems are independent, involve different brain regions, or overlap. To address this question we investigated whether the degree to which the voluntary action system is activated at the time of stimulus onset predicts reaction times to external stimuli. We recorded event-related potentials while participants prepared and executed left- or right-hand voluntary actions, which were occasionally interrupted by a stimulus requiring either a left- or right-hand response. In trials where participants successfully performed the stimulus-driven response, increased voluntary motor preparation was associated with faster responses on congruent trials (where participants were preparing a voluntary action with the same hand that was then required by the target stimulus), and slower responses on incongruent trials. This suggests that early hand-specific activity in medial frontal cortex for voluntary action trials can be used by the stimulus-driven system to speed responding. This finding questions the clear distinction between voluntary and stimulus-driven action systems. PMID- 22090495 TI - Sapap3 deletion causes mGluR5-dependent silencing of AMPAR synapses. AB - Synaptic transmission mediated by AMPA-type glutamate receptors (AMPARs) is regulated by scaffold proteins in the postsynaptic density. SAP90/PSD-95 associated protein 3 (SAPAP3) is a scaffold protein that is highly expressed in striatal excitatory synapses. While loss of SAPAP3 is known to cause obsessive compulsive disorder-like behaviors in mice and reduce extracellular field potentials in the striatum, the mechanism by which SAPAP3 regulates excitatory neurotransmission is largely unknown. This study demonstrates that Sapap3 deletion reduces AMPAR-mediated synaptic transmission in striatal medium spiny neurons (MSNs) through postsynaptic endocytosis of AMPARs. Striatal MSNs in Sapap3 KO mice have fewer synapses with AMPAR activity and a higher proportion of silent synapses. We further find that increased metabotropic glutamate receptor 5 (mGluR5) activity in Sapap3 KO mice underlies the decrease in AMPAR synaptic transmission and excessive synapse silencing. These findings suggest a model whereby the normal role of SAPAP3 is to inhibit mGluR5-driven endocytosis of AMPARs. The results of this study provide the first evidence for the mechanism by which the SAPAP family of scaffold proteins regulates AMPAR synaptic activity. PMID- 22090497 TI - Behavioral state modulates the activity of brainstem sensorimotor neurons. AB - Sensorimotor processing must be modulated according to the animal's behavioral state. A previous study demonstrated that motion responses were strongly state dependent in birds. Vestibular eye and head responses were significantly larger and more compensatory during simulated flight, and a flight-specific vestibular tail response was also characterized. In the current study, we investigated the neural substrates for these state-dependent vestibular behaviors by recording extracellularly from neurons in the vestibular nuclear complex and comparing their spontaneous activity and sensory responses during default and simulated flight states. We show that motion-sensitive neurons in the lateral vestibular nucleus are state dependent. Some neurons increased their spontaneous firing rates during flight, though their increased excitability was not reflected in higher sensory gains. However, other neurons exhibited state-dependent gating of sensory inputs, responding to rotational stimuli only during flight. These results demonstrate that vestibular processing in the brainstem is state dependent and lay the foundation for future studies to investigate the synaptic mechanisms responsible for these modifications. PMID- 22090498 TI - Perinatal citalopram exposure selectively increases locus ceruleus circuit function in male rats. AB - Selective serotonin reuptake inhibitors (SSRIs), such as citalopram (CTM), have been widely prescribed for major depressive disorder, not only for adult populations, but also for children and pregnant mothers. Recent evidence suggests that chronic SSRI exposure in adults increases serotonin (5-HT) levels in the raphe system and decreases norepinephrine (NE) locus ceruleus (LC) neural activity, suggesting a robust opposing interaction between these two monoamines. In contrast, perinatal SSRI exposure induces a long-lasting downregulation of the 5-HT-raphe system, which is opposite to that seen with chronic adult treatment. Therefore, the goal of the present investigation was to test the hypothesis that perinatal CTM exposure (20 mg/kg/d) from postnatal day 1 (PN1) to PN10 leads to hyperexcited NE-LC circuit function in adult rats (>PN90). Our single-neuron LC electrophysiological data demonstrated an increase in spontaneous and stimulus driven neural activity, including an increase in phasic bursts in CTM-exposed animals. In addition, we demonstrated a corresponding immunoreactive increase in the rate-limiting catalyzing catecholamine enzyme (tyrosine hydroxylase) within the LC and their neocortical target sites compared to saline controls. Moreover, these effects were only evident in male exposed rats, suggesting a sexual dimorphism in neural development after SSRI exposure. Together, these results indicate that administration of SSRIs during a sensitive period of brain development results in long-lasting alterations in NE-LC circuit function in adults and may be useful in understanding the etiology of pervasive developmental disorders such as autism spectrum disorder. PMID- 22090499 TI - Neuronal P2X2 receptors are mobile ATP sensors that explore the plasma membrane when activated. AB - ATP-gated ionotropic P2X2 receptors are widely expressed in neurons. Although the electrophysiological properties of P2X2 receptors have been extensively studied, little is known about the plasma membrane lateral mobility of P2X2 receptors or whether receptor mobility is regulated by ATP. Here we used single-molecule imaging with simultaneous whole-cell voltage-clamp recordings to track quantum dot-labeled P2X2 receptors in the dendrites of rat hippocampal neurons to explore P2X2 receptor mobility and its regulation. We find that plasma membrane P2X2 receptor lateral mobility in dendrites is heterogeneous but mostly Brownian in nature, consisting of mobile and slowly mobile receptor pools. Moreover, lateral mobility is P2X2 subunit and cell specific, is increased in an activation dependent manner, and is regulated by cytosolic VILIP1, a calcium binding protein. Our data provide the first direct measures of P2X receptor mobility and show that P2X2 receptors are mobile ATP sensors, sampling more of the dendritic plasma membrane in response to ATP. PMID- 22090500 TI - "Small axonless neurons": postnatally generated neocortical interneurons with delayed functional maturation. AB - GABAergic interneurons of the mouse cortex are generated embryonically in the ventral telencephalon. Recent evidence, however, indicated that a subset of cortical cells expressing interneuronal markers originate in the neonatal subventricular zone. This has raised interest in the functional development and incorporation of these postnatally generated cells into cortical circuits. Here we demonstrate that these cells integrate in the cortex, and that they constitute two distinct GABAergic interneuronal classes. Whereas one class reflects the tail end of embryonic interneuron genesis, the other class comprises interneurons that are exclusively generated perinatally and postnatally. The latter constitute a novel subclass of interneurons. They are preferentially located in the deeper layers of the olfactory and orbital cortices, exhibit a unique firing pattern and slow functional maturation. Based on their distinct morphology we termed them "small axonless neurons" and indeed, unlike other cortical neurons, they communicate with their neuronal partners via dendrodendritic synapses. Finally, we provide evidence that the number of small axonless neurons is enhanced by odor enrichment, a further indication that they integrate into neural circuits and participate to olfactory processing. PMID- 22090501 TI - Distinct mechanisms underlying pronociceptive effects of opioids. AB - In addition to analgesia, opioids may also produce paradoxical pain amplification [opioid-induced hyperalgesia (OIH)] either on abrupt withdrawal or during continuous long-term application. Here, we assessed antinociceptive and pronociceptive effects of three clinically used opioids at C-fiber synapses in the rat spinal dorsal horn in vivo. During 60 min of intravenous infusions of remifentanil (450 MUg.kg-1.h-1), fentanyl (48 MUg.kg-1.h-1), or morphine (14 mg.kg-1.h-1), C-fiber-evoked field potentials were depressed and paired-pulse ratios (PPR) were increased, indicating a presynaptic inhibition by all three opioids. After withdrawal, postsynaptic responses were enhanced substantially for the remaining of the recording periods of at least 3 h. Withdrawal from remifentanil led to long-term potentiation (LTP) of synaptic strength in C-fibers via activation of spinal MU-opioid receptors (MORs) and spinal NMDA receptors (NMDARs). Fentanyl and morphine caused an enhancement of synaptic transmission at C-fibers, which involved two distinct mechanisms: (1) an opioid withdrawal LTP that also required activation of spinal MORs and NMDARs and that was associated with a decrease in PPR suggestive of a presynaptic mechanism of its expression, and (2) an immediate-onset, descending facilitation of C-fiber-evoked field potentials during and after intravenous infusion of fentanyl and morphine. Immediate-onset, descending facilitation was mediated by the activation of extraspinal MORs, descending serotonergic pathways, and spinal 5 hydroxytryptamine-3 receptors (5-HT3Rs). Our study identified fundamentally different pronociceptive effects of clinically used opioids and suggests that OIH can be prevented by the combined use of NMDAR and 5-HT3R antagonists. PMID- 22090502 TI - A novel functionally distinct subtype of striatal neuropeptide Y interneuron. AB - We investigated the properties of neostriatal neuropeptide Y (NPY)-expressing interneurons in transgenic GFP (green fluorescent protein)-NPY reporter mice. In vitro whole-cell recordings and biocytin staining demonstrated the existence of a novel class of neostriatal NPY-expressing GABAergic interneurons that exhibit electrophysiological, neurochemical, and morphological properties strikingly different from those of previously described NPY-containing, plateau depolarization low-threshold spike (NPY-PLTS) interneurons. The novel NPY interneuron type (NPY-neurogliaform) differed from previously described NPY-PLTS interneurons by exhibiting a significantly lower input resistance and hyperpolarized membrane potential, regular, nonaccommodating spiking in response to depolarizing current injections, and an absence of plateau depolarizations or low-threshold spikes. NPY-neurogliaform interneurons were also easily distinguished morphologically by their dense, compact, and highly branched dendritic and local axonal arborizations that contrasted sharply with the sparse and extended axonal and dendritic arborizations of NPY-PLTS interneurons. Furthermore, NPY-neurogliaform interneurons did not express immunofluorescence for somatostatin or nitric oxide synthase that was ubiquitous in NPY-PLTS interneurons. IPSP/Cs could only rarely be elicited in spiny projection neurons (SPNs) in paired recordings with NPY-PLTS interneurons. In contrast, the probability of SPN innervation by NPY-neurogliaform interneurons was extremely high, the synapse very reliable (no failures were observed), and the resulting postsynaptic response was a slow, GABA(A) receptor-mediated IPSC that has not been previously described in striatum but that has been elicited from NPY GABAergic neurogliaform interneurons in cortex and hippocampus. These properties suggest unique and distinctive roles for NPY-PLTS and NPY-neurogliaform interneurons in the integrative properties of the neostriatum. PMID- 22090503 TI - Use dependence of presynaptic tenacity. AB - Recent studies indicate that synaptic vesicles (SVs) are continuously interchanged among nearby synapses at very significant rates. These dynamics and the lack of obvious barriers confining synaptic vesicles to specific synapses would seem to challenge the ability of synapses to maintain a constant amount of synaptic vesicles over prolonged time scales. Moreover, the extensive mobilization of synaptic vesicles associated with presynaptic activity might be expected to intensify this challenge. Here we examined the ability of individual presynaptic boutons of rat hippocampal neurons to maintain their synaptic vesicle content, and the degree to which this ability is affected by continuous activity. We found that the synaptic vesicle content of individual boutons belonging to the same axons gradually changed over several hours, and that these changes occurred independently of activity. Intermittent stimulation for 1 h accelerated rates of vesicle pool size change. Interestingly, however, following stimulation cessation, vesicle pool size change rates gradually converged with basal change rates. Over similar time scales, active zones (AZs) exhibited substantial remodeling; yet, unlike synaptic vesicles, AZ remodeling was not affected by the stimulation paradigms used here. These findings indicate that enhanced activity levels can increase synaptic vesicle redistribution among nearby synapses, but also highlight the presence of forces that act to restore particular set points in terms of SV contents, and support a role for active zones in preserving such set points. These findings also indicate, however, that neither AZ size nor SV content set points are particularly stable, questioning the long-term tenacity of presynaptic specializations. PMID- 22090504 TI - CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth. AB - The cysteine-rich protein (CRP) family is a subgroup of LIM domain proteins. CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells. Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons. Knockdown of CRP1 expression by short hairpin RNA interference results in inhibition of filopodia formation and dendritic growth in neurons. Overexpression of CRP1 increases filopodia formation and neurite branching, which require its actin-bundling activity. Expression of CRP1 with a constitutively active form of Cdc42, a GTPase involved in filopodia formation, increases filopodia formation in COS-7 cells, suggesting cooperation between the two proteins. Moreover, we demonstrate that neuronal activity upregulates CRP1 expression in hippocampal neurons via Ca2+ influx after depolarization. Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein mediate the Ca2+-induced upregulation of CRP1 expression. Furthermore, CRP1 is required for the dendritic growth induced by Ca2+ influx or CaMKIV. Together, these data are the first to demonstrate a role for CRP1 in dendritic growth. PMID- 22090505 TI - An essential role for RAX homeoprotein and NOTCH-HES signaling in Otx2 expression in embryonic retinal photoreceptor cell fate determination. AB - The molecular mechanisms underlying cell fate determination from common progenitors in the vertebrate CNS remain elusive. We previously reported that the OTX2 homeoprotein regulates retinal photoreceptor cell fate determination. While Otx2 transactivation is a pivotal process for photoreceptor cell fate determination, its transactivation mechanism in the retina is unknown. Here, we identified an evolutionarily conserved Otx2 enhancer of ~500 bp, named embryonic enhancer locus for photoreceptor Otx2 transcription (EELPOT), which can recapitulate initial Otx2 expression in the embryonic mouse retina. We found that the RAX homeoprotein interacts with EELPOT to transactivate Otx2, mainly in the final cell cycle of retinal progenitors. Conditional inactivation of Rax results in downregulation of Otx2 expression in vivo. We also showed that NOTCH-HES signaling negatively regulates EELPOT to suppress Otx2 expression. These results suggest that the integrated activity of cell-intrinsic and -extrinsic factors on EELPOT underlies the molecular basis of photoreceptor cell fate determination in the embryonic retina. PMID- 22090506 TI - Lifelong bilingualism maintains white matter integrity in older adults. AB - Previous research has shown that bilingual speakers have higher levels of cognitive control than comparable monolinguals, especially at older ages. The present study investigates a possible neural correlate of this behavioral effect. Given that white matter (WM) integrity decreases with age in adulthood, we tested the hypothesis that bilingualism is associated with maintenance of WM in older people. Using diffusion tensor imaging, we found higher WM integrity in older people who were lifelong bilinguals than in monolinguals. This maintained integrity was measured by fractional anisotropy (FA) and was found in the corpus callosum extending to the superior and inferior longitudinal fasciculi. We also hypothesized that stronger WM connections would be associated with more widely distributed patterns of functional connectivity in bilinguals. We tested this by assessing the resting-state functional connectivity of frontal lobe regions adjacent to WM areas with group differences in FA. Bilinguals showed stronger anterior to posterior functional connectivity compared to monolinguals. These results are the first evidence that maintained WM integrity is related to lifelong naturally occurring experience; the resulting enhanced structural and functional connectivity may provide a neural basis for "brain reserve." PMID- 22090507 TI - HCN channels expressed in the inner ear are necessary for normal balance function. AB - HCN1-4 subunits form Na+/K+-permeable ion channels that are activated by hyperpolarization and carry the current known as I(h). I(h) has been characterized in vestibular hair cells of the inner ear, but its molecular correlates and functional contributions have not been elucidated. We examined Hcn mRNA expression and immunolocalization of HCN protein in the mouse utricle, a mechanosensitive organ that contributes to the sense of balance. We found that HCN1 is the most highly expressed subunit, localized to the basolateral membranes of type I and type II hair cells. We characterized I(h) using the whole-cell, voltage-clamp technique and found the current expressed in 84% of the cells with a mean maximum conductance of 4.4 nS. I(h) was inhibited by ZD7288, cilobradine, and by adenoviral expression of a dominant-negative form of HCN2. To determine which HCN subunits carried I(h), we examined hair cells from mice deficient in Hcn1, 2, or both. I(h) was completely abolished in hair cells of Hcn1-/- mice and Hcn1/2-/- mice but was similar to wild-type in Hcn2-/- mice. To examine the functional contributions of I(h), we recorded hair cell membrane responses to small hyperpolarizing current steps and found that activation of I(h) evoked a 5 10 mV sag depolarization and a subsequent 15-20 mV rebound upon termination. The sag and rebound were nearly abolished in Hcn1-deficient hair cells. We also found that Hcn1-deficient mice had deficits in vestibular-evoked potentials and balance assays. We conclude that HCN1 contributes to vestibular hair cell function and the sense of balance. PMID- 22090508 TI - Multimodal quantitative magnetic resonance imaging of thalamic development and aging across the human lifespan: implications to neurodegeneration in multiple sclerosis. AB - The human brain thalami play essential roles in integrating cognitive, sensory, and motor functions. In multiple sclerosis (MS), quantitative magnetic resonance imaging (qMRI) measurements of the thalami provide important biomarkers of disease progression, but late development and aging confound the interpretation of data collected from patients over a wide age range. Thalamic tissue volume loss due to natural aging and its interplay with lesion-driven pathology has not been investigated previously. In this work, we used standardized thalamic volumetry combined with diffusion tensor imaging, T2 relaxometry, and lesion mapping on large cohorts of controls (N = 255, age range = 6.2-69.1 years) and MS patients (N = 109, age range = 20.8-68.5 years) to demonstrate early age- and lesion-independent thalamic neurodegeneration. PMID- 22090509 TI - A distinct contribution of short-wavelength-sensitive cones to light-evoked activity in the mouse pretectal olivary nucleus. AB - Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) combine inputs from outer-retinal rod/cone photoreceptors with their intrinsic phototransduction machinery to drive a wide range of so-called non image-forming (NIF) responses to light. Defining the contribution of each photoreceptor class to evoked responses is vital for determining the degree to which our sensory capabilities depend on melanopsin and for optimizing NIF responses to benefit human health. We addressed this problem by recording electrophysiological responses in the mouse pretectal olivary nucleus (PON) (a target of ipRGCs and origin of the pupil light reflex) to a range of gradual and abrupt changes in light intensity. Dim stimuli drove minimal changes in PON activity, suggesting that rods contribute little under these conditions. To separate cone from melanopsin influences, we compared responses to short (460 nm) and longer (600/655 nm) wavelengths in mice carrying a red shifted cone population (Opn1mw(r)) or lacking melanopsin (Opn4-/-). Our data reveal a surprising difference in the quality of information available from medium- and short-wavelength-sensitive cones. The majority cone population (responsive to 600/655 nm) supported only transient changes in firing and responses to relatively sudden changes in light intensity. In contrast, cones uniquely sensitive to the shorter wavelength (S-cones) were better able to drive responses to gradual changes in illuminance, contributed a distinct off inhibition, and at least partially recapitulated the ability of melanopsin to sustain responses under continuous illumination. These data reveal a new role for S-cones unrelated to color vision and suggest renewed consideration of cone contributions to NIF vision at shorter wavelengths. PMID- 22090510 TI - 5-HT(3A) receptor-bearing white matter interstitial GABAergic interneurons are functionally integrated into cortical and subcortical networks. AB - In addition to axons and surrounding glial cells, the corpus callosum also contains interstitial neurons that constitute a heterogeneous cell population. There is growing anatomical evidence that white matter interstitial cells (WMICs) comprise GABAergic interneurons, but so far there is little functional evidence regarding their connectivity. The scarcity of these cells has hampered electrophysiological studies. We overcame this hindrance by taking recourse to transgenic mice in which distinct WMICs expressed enhanced green fluorescence protein (EGFP). The neuronal phenotype of the EGFP-labeled WMICs was confirmed by their NeuN positivity. The GABAergic phenotype could be established based on vasoactive intestinal peptide and calretinin expression and was further supported by a firing pattern typical for interneurons. Axons and dendrites of many EGFP labeled WMICs extended to the cortex, hippocampus, and striatum. Patch-clamp recordings in acute slices showed that they receive excitatory and inhibitory input from cortical and subcortical structures. Moreover, paired recordings revealed that EGFP-labeled WMICs inhibit principal cells of the adjacent cortex, thus providing unequivocal functional evidence for their GABAergic phenotype and demonstrating that they are functionally integrated into neuronal networks. PMID- 22090512 TI - Multiple reference frames in cortical oscillatory activity during tactile remapping for saccades. AB - Single-unit recordings have shown that the brain uses multiple reference frames in spatial processing. The brain could use this neural architecture to implicitly create multiple modes of representation at the population level, with each reference frame weighted as a function of task demands. Using magnetoencephalography, we tested this hypothesis by studying the reference frames in rhythmic neuronal synchronization--a population measure--during tactile remapping for saccades. Human subjects fixated either to the left or right of the body midline, while a tactile stimulus was applied to an invisible fingertip, located either left or right of fixation. After a variable delay, they looked at the remembered stimulus location. Results show a transient body-centered, stimulus-induced gamma-band response (70-90 Hz) in somatosensory areas, contralateral to the stimulated hand. Concurrently, a gamma-band response occurred in posterior parietal cortex (PPC), contralateral to the gaze-centered location of the stimulus, even though the stimulus was not seen. The temporal overlap of these early representations suggests that there is a fast bottom-up sensory-induced remapping in PPC, taking into account the relative positions of eyes and hand. The gaze-centered representation in PPC was sustained in a high gamma range (85-115 Hz) and increased in power closer to the initiation of the saccade. Lower-frequency rhythms (alpha, beta) showed body-centered power modulations in somatosensory areas in anticipation of the stimulus and a mixture of reference frames in PPC after stimulus presentation. We conclude that oscillatory activity reflects the time-varying coding of information in body- and gaze-centered reference frames during tactile remapping for saccades. PMID- 22090511 TI - Fast-activating voltage- and calcium-dependent potassium (BK) conductance promotes bursting in pituitary cells: a dynamic clamp study. AB - The electrical activity pattern of endocrine pituitary cells regulates their basal secretion level. Rat somatotrophs and lactotrophs exhibit spontaneous bursting and have high basal levels of hormone secretion, while gonadotrophs exhibit spontaneous spiking and have low basal hormone secretion. It has been proposed that the difference in electrical activity between bursting somatotrophs and spiking gonadotrophs is due to the presence of large conductance potassium (BK) channels on somatotrophs but not on gonadotrophs. This is one example where the role of an ion channel type may be clearly established. We demonstrate here that BK channels indeed promote bursting activity in pituitary cells. Blocking BK channels in bursting lacto-somatotroph GH4C1 cells changes their firing activity to spiking, while further adding an artificial BK conductance via dynamic clamp restores bursting. Importantly, this burst-promoting effect requires a relatively fast BK activation/deactivation, as predicted by computational models. We also show that adding a fast-activating BK conductance to spiking gonadotrophs converts the activity of these cells to bursting. Together, our results suggest that differences in BK channel expression may underlie the differences in electrical activity and basal hormone secretion levels among pituitary cell types and that the rapid rate of BK channel activation is key to its role in burst promotion. PMID- 22090513 TI - Stress-activated protein kinase MKK7 regulates axon elongation in the developing cerebral cortex. AB - The c-Jun NH(2)-terminal protein kinase (JNK), which belongs to the mitogen activated protein kinase family, plays important roles in a broad range of physiological processes. JNK is controlled by two upstream regulators, mitogen activated protein kinase kinase (MKK) 7 and MKK4. To elucidate the physiological functions of MKK7, we used Nestin-Cre to generate a novel mouse model in which the mkk7 gene was specifically deleted in the nervous system (Mkk7(flox/flox) Nestin-Cre mice). These mice were indistinguishable from their control littermates in gross appearance during embryogenesis but died immediately after birth without breathing. Histological examination showed that the mutants had severe defects in brain development, including enlarged ventricles, reduced striatum, and minimal axon tracts. Electron microscopy revealed abnormal accumulations of filamentous structures and autophagic vacuoles in Mkk7(flox/flox) Nestin-Cre brain. Further analysis showed that MKK7 deletion decreased numbers of TAG-1-expressing axons and delayed neuronal migration in the cerebrum. Neuronal differentiation was not altered. In utero electroporation studies showed that contralateral projection of axons by layer 2/3 neurons was impaired in the absence of MKK7. Moreover, MKK7 regulated axon elongation in a cell-autonomous manner in vivo, a finding confirmed in vitro. Finally, phosphorylation levels of JNK substrates, including c-Jun, neurofilament heavy chain, microtubule-associated protein 1B, and doublecortin, were reduced in Mkk7(flox/flox) Nestin-Cre brain. Our findings demonstrate that the phenotype of Mkk7(flox/flox) Nestin-Cre mice differs substantially from that of Mkk4(flox/flox) Nestin-Cre mice, and establish that MKK7-mediated regulation of JNK is uniquely critical for both axon elongation and radial migration in the developing brain. PMID- 22090514 TI - Authentically phosphorylated alpha-synuclein at Ser129 accelerates neurodegeneration in a rat model of familial Parkinson's disease. AB - Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the appearance of fibrillar aggregates of insoluble alpha-synuclein (alpha-syn) called Lewy bodies (LBs). Approximately 90% of alpha syn deposited in LBs is phosphorylated at serine 129 (Ser129). In contrast, only 4% of total alpha-syn is phosphorylated in normal brain, suggesting that accumulation of Ser129-phosphorylated alpha-syn is involved in the pathogenesis of PD. However, the role of Ser129 phosphorylation in alpha-syn neurotoxicity remains unclear. In this study, we coexpressed familial PD-linked A53T alpha-syn and G-protein-coupled receptor kinase 6 (GRK6) in the rat SN pars compacta using recombinant adeno-associated virus 2. Coexpression of these proteins yielded abundant Ser129-phosphorylated alpha-syn and significantly exacerbated degeneration of dopaminergic neurons when compared with coexpression of A53T alpha-syn and GFP. Immunohistochemical analysis revealed that Ser129 phosphorylated alpha-syn was preferentially distributed to swollen neurites. However, biochemical analysis showed that the increased expression of Ser129 phosphorylated alpha-syn did not promote accumulation of detergent-insoluble alpha-syn. Coexpression of catalytically inactive K215R mutant GRK6 failed to accelerate A53T alpha-syn-induced degeneration. Furthermore, introducing a phosphorylation-incompetent mutation, S129A, into A53T alpha-syn did not alter the pace of degeneration, even when GRK6 was coexpressed. Our study demonstrates that authentically Ser129-phosphorylated alpha-syn accelerates A53T alpha-syn neurotoxicity without the formation of detergent-insoluble alpha-syn, and suggests that the degenerative process could be constrained by inhibiting the kinase that phosphorylates alpha-syn at Ser129. PMID- 22090515 TI - Collaborations in population-based health research: the 17th annual HMO Research Network Conference, March 23-25, 2011, Boston, Massachusetts, USA. AB - The HMO Research Network (HMORN) is a consortium of 16 health care systems with integrated research centers. Approximately 475 people participated in its 17(th) annual conference, hosted by the Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School. The theme, "Collaborations in Population-Based Health Research," reflected the network's emphasis on collaborative studies both among its members and with external investigators. Plenary talks highlighted the initial phase of the HMORN's work to establish the NIH-HMO Collaboratory, opportunities for public health collaborations, the work of early career investigators, and the state of the network. Platform and poster presentations showcased a broad spectrum of innovative public domain research in areas including disease epidemiology and treatment, health economics, and information technology. Special interest group sessions and ancillary meetings provided venues for informal conversation and structured work among ongoing groups, including networks in cancer, cardiovascular diseases, lung diseases, medical product safety, and mental health. PMID- 22090660 TI - Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. AB - AIMS More intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal bleeding complications in the PLATO study. METHODS AND RESULTS PLATO was a randomized, double-blind, active control international, phase 3 clinical trial in patients with acute ST elevation and non-ST-segment elevation ACS. A total of 18 624 patients were randomized to either ticagrelor, a non-thienopyridine, reversibly binding platelet P2Y(12) receptor antagonist, or clopidogrel in addition to aspirin. Patients randomized to ticagrelor and clopidogrel had similar rates of PLATO major bleeding (11.6 vs. 11.2%; P = 0.43), TIMI major bleeding (7.9 vs. 7.7%, P = 0.56) and GUSTO severe bleeding (2.9 vs. 3.1%, P = 0.22). Procedure-related bleeding rates were also similar. Non-CABG major bleeding (4.5 vs. 3.8%, P = 0.02) and non-procedure-related major bleeding (3.1 vs. 2.3%, P = 0.05) were more common in ticagrelor-treated patients, primarily after 30 days on treatment. Fatal bleeding and transfusion rates did not differ between groups. There were no significant interactions for major bleeding or combined minor plus major bleeding between treatment groups and age >=75 years, weight <60 kg, region, chronic kidney disease, creatinine clearance <60 mL/min, aspirin dose >325 mg on the day of randomization, pre-randomization clopidogrel administration, or clopidogrel loading dose. CONCLUSION Ticagrelor compared with clopidogrel was associated with similar total major bleeding but increased non-CABG and non-procedure-related major bleeding, primarily after 30 days on study drug treatment. Fatal bleeding was low and did not differ between groups. PMID- 22090661 TI - Aspirin for primary prevention of vascular events in women: individualized prediction of treatment effects. AB - AIMS To identify women who benefit from aspirin 100 mg on alternate days for primary prevention of vascular events by using treatment effect prediction based on individual patient characteristics. METHODS AND RESULTS Randomized controlled trial data from the Women's Health Study were used to predict treatment effects for individual women in terms of absolute risk reduction for major cardiovascular events (i.e. myocardial infarction, stroke, or cardiovascular death). Predictions were based on existing risk scores, i.e. Framingham (FRS), and Reynolds (RRS), and on a newly developed prediction model. The net benefit of different aspirin treatment-strategies was compared: (i) treat no one, (ii) treat everyone, (iii) treatment according to the current guidelines (i.e. selective treatment of women >65 years of age or having >10% FRS), and (iv) prediction-based treatment (i.e. selective treatment of patients whose predicted treatment effect exceeds a given decision threshold). The predicted reduction in 10-year absolute risk for major cardiovascular events was <1% in 97.8% of 27 939 study subjects when based on the refitted FRS, in 97.0% when based on the refitted RRS, and in 90.0% when based on the newly developed model. Of the treatment strategies considered, only prediction-based treatment using the newly developed model and selective treatment of women >65 years of age yielded more net benefit than treating no one, provided that the 10-year number-willing-to-treat (NWT) to prevent one cardiovascular event was above 50. CONCLUSION Aspirin was ineffective or even harmful in the majority of patients. Age was positively related to treatment effect, whereas current smoking and baseline risk for cardiovascular events were not. When the NWT is 50 or lower, the aspirin treatment strategy that is associated with optimal net benefit in primary prevention of vascular events in women is to treat none. PMID- 22090662 TI - Cyclicality, Mortality, and the Value of Time: The Case of Coffee Price Fluctuations and Child Survival in Colombia. AB - Recent studies demonstrate procyclical mortality in wealthy countries, but there are reasons to expect a countercyclical relationship in developing nations. We investigate how child survival in Colombia responds to fluctuations in world Arabica coffee prices - and document starkly procyclical child deaths. In studying this result's behavioral underpinnings, we highlight that: (1) The leading determinants of child health are inexpensive but require considerable time, and (2) As the value of time declines with falling coffee prices, so does the relative price of health. We find a variety of direct evidence consistent with the primacy of time in child health production. PMID- 22090663 TI - MAOS ls for the general synthesis and lead optimization of 3,6-disubstituted [1,2,4]triazolo[4,3-b]pyridazines. AB - General, high-yielding MAOS protocols for the expedient synthesis of functionalized 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines are described amenable to an iterative analog library synthesis strategy for the lead optimization of an M1 antagonist screening hit. Optimized compounds proved to be highly selective M1 antagonists. PMID- 22090664 TI - Mental Healthcare Disparities Disparities Affect Treatment of Black Adolescents. PMID- 22090665 TI - Generalized Degrees of Freedom and Adaptive Model Selection in Linear Mixed Effects Models. AB - Linear mixed-effects models involve fixed effects, random effects and covariance structure, which require model selection to simplify a model and to enhance its interpretability and predictability. In this article, we develop, in the context of linear mixed-effects models, the generalized degrees of freedom and an adaptive model selection procedure defined by a data-driven model complexity penalty. Numerically, the procedure performs well against its competitors not only in selecting fixed effects but in selecting random effects and covariance structure as well. Theoretically, asymptotic optimality of the proposed methodology is established over a class of information criteria. The proposed methodology is applied to the BioCycle study, to determine predictors of hormone levels among premenopausal women and to assess variation in hormone levels both between and within women across the menstrual cycle. PMID- 22090666 TI - An Evolution of Communication Modalities: Very Young Cochlear Implant Users who Transitioned from Sign to Speech During the First Years of Use. AB - The communication modalities used, and the articulation and aural-only receptive vocabulary skills were investigated in 19 prelingually profoundly deaf infants who initially utilized Total Communication and who were implanted between the ages of 12 and 29m. Results revealed the children overwhelmingly tended to use voice only modality for an expressive task. Additionally articulation and receptive vocabulary skills approached those of normal hearing peers. Implications of these findings and suggestions for future studies are provided. PMID- 22090667 TI - Indians can do better at improving child survival. PMID- 22090668 TI - Social audit in health sector planning and program implementation in India. PMID- 22090669 TI - Public health education in India: need and demand paradox. PMID- 22090670 TI - Relationship of Psychosocial Risk Factors, Certain Personality Traits and Myocardial Infarction in Indians: A Case-control Study. AB - OBJECTIVE: To investigate the relationship of psychosocial factors (lack of social support, stress and subjective well-being) and personality traits with myocardial infarction (MI). MATERIALS AND METHODS: A case-control study involving 100 cases and 100 matched controls was conducted in Lok Nayak Hospital, New Delhi. RESULTS: Stress over 1 year was significantly higher in cases (P < 0.001). However, difference was not significant when scores of social support (P = 0.2), Presumptive Stressful Life Event (PSLE) over lifetime (P = 0.058) and subjective well-being (P = 0.987) were compared. MI was significantly associated with hyperactive (P < 0.001), dominant (P = 0.03), egoistic (P < 0.001) and introvert (P < 0.001) personalities. CONCLUSION: Certain personality traits and recent stress may be important risk factors of MI, especially in Indians. The finding may have implications on the preventive strategies planned for MI patients. PMID- 22090671 TI - A Study of the Swine Flu (H1N1) Epidemic Among Health Care Providers of a Medical College Hospital of Delhi. AB - BACKGROUND: Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. Understanding the role of specific perceptions in motivating people to engage in precautionary behavior may help health communicators to improve their messages about outbreaks of new infectious disease generally and swine flu specifically. OBJECTIVES: To study the knowledge and practices of health care providers regarding swine flu and to study the attitudes and practices of health care providers toward the prevention of the swine flu epidemic. MATERIALS AND METHODS: The present study was a cross sectional (descriptive) study and was conducted in the month of September, 2009, among doctors and nurses. A maximum of 40% of the total health care providers of GTB Hospital were covered because of feasibility and logistics, and, therefore, the sample size was 334. RESULTS: Around 75% of the health care providers were aware about the symptoms of swine flu. Mostly, all study subjects were aware that it is transmitted through droplet infection. Correct knowledge of the incubation period of swine flu was known to 80% of the doctors and 69% of the nurses. Knowledge about high-risk groups (contacts, travelers, health care providers) was observed among 88% of the doctors and 78.8% of the nurses. Practice of wearing mask during duty hours was observed among 82.6% of doctors and 85% of nurses, whereas of the total study population, only 40% were correctly using mask during duty hours. CONCLUSIONS: Significant gaps observed between knowledge and actual practice of the Health Care Provider regarding swine flu need to be filled by appropriate training. Data indicate that the health care providers are very intellectual, but they do not themselves practice what they preach. PMID- 22090672 TI - Non-pharmacological Interventions in Hypertension: A Community-based Cross-over Randomized Controlled Trial. AB - BACKGROUND: Hypertension is the most prevalent non-communicable disease causing significant morbidity/mortality through cardiovascular, cerebrovascular, and renal complications. OBJECTIVES: This community-based study tested the efficacy of non-pharmacological interventions in preventing/controlling hypertension. MATERIALS AND METHODS: This is a cross-over randomized controlled trial (RCT) of the earlier RCT (2007) of non-pharmacological interventions in hypertension, conducted in the urban service area of our Institute. The subjects, prehypertensive and hypertensive young adults (98 subjects: 25, 23, 25, 25 in four groups) were randomly allotted into a group that he/she had not belonged to in the earlier RCT: Control (New Group I), Physical Exercise (NG II)-brisk walking for 50 to 60 minutes, three to four days/week, Salt Intake Reduction (NG III) to at least half of their previous intake, Yoga (NG IV) for 30 to 45 minutes/day, five days/week. Blood pressure was measured before and after eight weeks of intervention. Analysis was by ANOVA with a Games-Howell post hoc test. RESULTS: Ninety-four participants (25, 23, 21, 25) completed the study. All three intervention groups showed significant reduction in BP (SBP/DBP mmHg: 5.3/6.0 in NG II, 2.5/2.0 in NG III, and 2.3/2.4 in NG IV, respectively), while the Control Group showed no significant difference. Persistence of significant reduction in BP in the three intervention groups after cross-over confirmed the biological plausibility of these non-pharmacological interventions. This study reconfirmed that physical exercise was more effective than Salt Reduction or Yoga. Salt Reduction, and Yoga were equally effective. CONCLUSION: Physical exercise, salt intake reduction, and yoga are effective non-pharmacological methods for reducing blood pressure in young pre-hypertensive and hypertensive adults. PMID- 22090673 TI - A study on consciousness of adolescent girls about their body image. AB - BACKGROUND: Perceived body image is an important potential predictor of nutritional status. Body image misconception during adolescence is unexplored field in Indian girls. OBJECTIVES: To study the consciousness of adolescent girls about their body image. MATERIALS AND METHODS: This multistage observational study was conducted on 586 adolescent girls of age 10-19 years in Lucknow district (151 from rural, 150 from slum, and 286 from urban area) of Uttar Pradesh, India. Information on desired and actual body size was collected with the help of predesigned questionnaire. RESULTS: 20.5% of studied girls show aspiration to become thin, who already perceived their body image as too thin. 73.4% adolescent girls were satisfied with their body image, while 26.6% were dissatisfied. The dissatisfaction was higher among girls of urban (30.2%) and slum (40.0%) areas in comparison to rural (22.5%) area. Percentage of satisfied girls was less in the 13-15 years (69.9%) age groups in comparison to 10-12 years (76.5%) and 16-19 years (76.4%). Among girls satisfied with their body image, 32.8% girls were found underweight, and 38.4% were stunted. Underweight girls (42.1%) and stunted girls (64.9%) were higher in number within satisfied girls of slum area. Among all of these adolescent girls, 32.8% of girls had overestimated their weight, while only 4.9% of girls had underestimated their weight. CONCLUSIONS: This study concludes that desire to become thin is higher in adolescent girls, even in those who already perceived their body image as too thin. PMID- 22090674 TI - Quality of life and its determinants in people living with human immunodeficiency virus infection in puducherry, India. AB - CONTEXT: With anti-retroviral therapy (ART) for human immunodeficiency virus infection (HIV) coming into picture, quality of life (QOL) has gained importance. Knowledge on the factors affecting QOL would be helpful in making important policy decisions and health care interventions. AIMS: The aim of this study is to assess the quality of life of people living with HIV (PLWH) and to identify the factors influencing their QOL. MATERIALS AND METHODS: The study was done among 200 PLWH attending a tertiary care hospital, and three Non Governmental Organizations at Puducherry, India, from November 2005 to May 2007. QOL was assessed using HIV specific World Health Organization Quality Of Life scale (WHOQOL-HIV) - BREF questionnaire which has six domains (physical, psychological, level of independence, social relationships, environment and spirituality/religiousness/personal belief). Social support and stigma were measured using "Multidimensional Scale of Perceived Social Support" and "HIV Stigma Scale," respectively, using Likert Scale. Factors influencing QOL were identified using backward stepwise multiple linear regression with the six domain scores as the dependent variables. RESULTS: MALE: Female ratio was 1:1 and 58% were in early stage of the disease (stage I/II). Psychological and SRPB (Spirituality Religiousness and Personal Beliefs) domains were the most affected domains. All the regression models were statistically significant (P<0.05). The determination coefficient was highest for the social relationship domain (57%) followed by the psychological domain (51%). Disease stage and perceived social support significantly influenced all the domains of WHOQOL. Younger age, female gender, rural background, shorter duration of HIV, non-intake of ART and greater HIV related stigma were the high risk factors of poor QOL. CONCLUSION: Interventions such as ART, family, vocational and peer counseling would address these modifiable factors influencing QOL, thereby improving the QOL of PLWH. PMID- 22090675 TI - Association of blindness and hearing impairment with mortality in a cohort of elderly persons in a rural area. AB - BACKGROUND: Studies in developed nations have reported an association of blindness and hearing impairment with mortality in elderly persons. OBJECTIVES: To study the association of blindness and hearing impairment with mortality in a cohort of elderly persons in rural north India. MATERIALS AND METHODS: This community-based prospective study was conducted in eleven randomly selected villages, in Ballabgarh block, Haryana. A cohort of 1422 participants, of age 60 years and above, was examined at baseline, for their visual and hearing status. Data on the sociodemographic factors, various comorbidities, activities of daily living, and self-rated health were recorded. Baseline data was collected for the period May 2008 to August 2008. Follow-up data collection for mortality was completed in December 2009. The median follow-up period was 518 days. RESULTS: One hundred out of 1422 elderly (7.0%) participants died during the follow-up period. Significant hazard ratios were found after adjustment for various comorbid conditions. On adjustment for sociodemographic factors (age, sex, and literacy), neither blindness nor hearing impairment was found to be significantly associated with mortality. After adjustment for all covariates in the study, hearing impairment (Hazard Ratio = 2.13; 95% CI, 1.29 - 3.54) was found to be significantly associated with mortality in the age group >=70 years. CONCLUSIONS: This study demonstrated that hearing impairment was an independent risk factor for mortality in people aged >=70 years. Similar studies with a longer period of follow-up are required in India, to guide public health interventions. PMID- 22090676 TI - Maternal Deaths in a Tertiary Health Care Centre of Odisha: An In-depth Study Supplemented by Verbal Autopsy. AB - BACKGROUND: Maternal mortality is a reflection of the care given to women by its society. It is tragic that deaths occur during the natural process of child birth and most of them are preventable. OBJECTIVES: The present study was undertaken to find out the causes and contributing factors of maternal deaths. MATERIALS AND METHODS: All maternal deaths occurring in a year in the medical college and hospital were traced and interviews were taken from the relatives as well as the health care providers who were present at the time of death of the woman. RESULTS: Out of the total maternal deaths, 72% belonged to 20-30 yrs age group, also 46.5% were illiterate, and majority deaths (60.5%) were from low socio economics status. Direct causes were responsible for 76.7% of maternal deaths. Hypertensive disorders of pregnancy were most common (32.6%) cause of direct deaths, while malaria (9.3%) and anemia (7%) were most common indirect causes. Most of the women had to use their own resources to travel to health care facilities. Delays at different levels, often in combination, contributed to the maternal deaths. CONCLUSIONS: The study will serve as an eye-opener to the bottlenecks present in the community as well as in the health facility so as to take appropriate measures to prevent maternal deaths. PMID- 22090677 TI - Hand hygiene compliance in the intensive care units of a tertiary care hospital. AB - CONTEXT: Hand hygiene (HH) is the most important measure to prevent hospital acquired infections but the compliance is still low. AIMS: To assess the compliance, identify factors influencing compliance and to study the knowledge, attitude and perceptions associated with HH among health care workers (HCW). SETTINGS AND DESIGN: Cross-sectional study conducted in 42 bedded Medical (Pulmonary, Medicine and Stroke) intensive care units (ICU) of a tertiary care hospital. MATERIALS AND METHODS: HCWs (doctors and nurses) were observed during routine patient care by observers posted in each ICU and their HH compliance was noted. Thereafter, questionnaire regarding knowledge, perception and attitudes toward HH was filled by each HCW. STATISTICAL ANALYSIS: Percentages and chi(2) test. RESULTS: The overall compliance was 43.2% (394/911 opportunities). It was 68.9% (31/45) in the intensivists, 56.3% (18/32) in attending physicians, 40.0% (28/70) in the postgraduate residents and 41.3% (301/728) in the nurses. Compliance was inversely related to activity index. Compliance for high, medium and low risk of cross-transmission was 38.8% (67/170), 43.8% (175/401) and 44.7% (152/340), respectively. CONCLUSIONS: Compliance of the study group is affected by the activity index (number of opportunities they come across per hour) and professional status. The HCWs listed less knowledge, lack of motivation, increased workload as some of the factors influencing HH. PMID- 22090678 TI - Domestic Violence against Nurses by their Marital Partners: A Facility-based Study at a Tertiary Care Hospital. AB - BACKGROUND: In recent times, domestic violence against women by marital partners has emerged as an important public health problem. OBJECTIVES: 1. To determine the prevalence, characteristics and impact of domestic violence against nurses by their marital partners, in Delhi, India. 2. To identify nurses' perceptions regarding acceptable behavior for men and women. MATERIALS AND METHODS: A facility-based pilot study was conducted at All India Institute of Medical Sciences (AIIMS), New Delhi. Data were collected using self-administered standardized questionnaire, among 60 ever married female nurses working at AIIMS hospital, selected by convenience sampling. The principal outcome variables were controlling behavior, emotional, physical and sexual violence by marital partners. Data were analyzed using SPSS 12 software. The test applied was Fisher's exact test and 1-sided Fisher's exact test. RESULTS: Sixty percent of nurses reported marital partner perpetrated controlling behavior, 65% reported emotional violence, 43.3% reported physical violence and 30% reported sexual violence. About 3/5(th) of nurses (58%) opined that no reason justified violence, except wife infidelity (31.67%). Of the physically or sexually abused respondents, 40% were ever injured, and 56.7% reported that violence affected their physical and mental health. CONCLUSION: There is a high magnitude of domestic violence against nurses and this is reported to have affected their physical and mental health. PMID- 22090679 TI - Coinfection of two age old diseases. PMID- 22090680 TI - Postpartum Blue is Common in Socially and Economically Insecure Mothers. PMID- 22090681 TI - Adverse drug events monitoring of live attenuated pandemic influenza vaccine. PMID- 22090682 TI - Modular teaching: an alternative to routine teaching method for undergraduate medical students. PMID- 22090683 TI - Work stress in first trimester causes low birth weight baby. PMID- 22090684 TI - Estimating catastrophic health expenditures: need for improved methodology and interpretation. PMID- 22090685 TI - Adolescent Tobacco Use and Role Model Influence: Interpreting it Right! PMID- 22090686 TI - One Year of Experience with H1N1 Infection: Clinical Observations from a Tertiary Care Hospital in Northern India. PMID- 22090687 TI - Intraoperative neurocytology of primary central nervous system neoplasia: A simplified and practical diagnostic approach. AB - Intraoperative consultations may pose considerable diagnostic challenge to the neuropathologist in diagnosing primary and metastatic neoplasms of the central nervous system (CNS). Cytological preparations in the form of squash, touch, imprint or smears are few of the available modalities in addition to the frozen section (FS). Although the latter is superior in providing both histologic patterns and cytomorphologic details yet smears are of vital importance when tissue available is limited (stereotactic biopsy), scrutinisation of intercellular matrix (astrocytoma versus oligodendroglioma) and evaluation of discohesive cells (lymphoma, pituitary adenoma) and in inflammatory lesions. This review is intended to emphasize the value, applicability and limitations of neurocytology aiming to expedite the intraoperative smear-based diagnoses of CNS neoplasia as per the World Health Organization (WHO) classification. We recommend that whenever possible, both smears and FS should be examined concomitantly and in a correlative manner. In the unlikely event of a mismatch between the findings on smear and FS, intraoperative diagnosis is primarily based on FS, if adequate tissue is available. However, each case must be evaluated on its own merit and in difficult cases relevant differential diagnoses should be offered to facilitate surgical decisions and optimally triage patient management. PMID- 22090688 TI - Defining the validity of classical and non-classical cellular changes indicative of low-grade squamous intraepithelial lesion encompassing human papillomavirus infection in relation to human papillomavirus deoxyribonucleic acid testing. AB - BACKGROUND: Human papillomavirus (HPV) infection as of now has been beyond doubt to be the causative agent for cervical carcinoma. Its morphological identification in Pap smear is important. AIM: To define the validity of classical and non-classical cellular changes indicative of low-grade squamous intraepithelial lesion (SIL) encompassing HPV infection in relation to positivity for 'high risk' HPV16 as well as for 'low risk' HPV6/11. MATERIALS AND METHODS: A total of 3000 Papanicolaou smears were screened, of which 150 were reported as low grade-SIL encompassing HPV infection (LSIL-HPV). Subsequently cervical scrapes from these 150 subjects, along with equal number of normal women as controls, were collected and processed for HPV deoxy-ribonucleic acid testing by polymerase chain reaction (PCR). RESULTS: ON THE BASIS OF CYTOMORPHOLOGICAL CHARACTERISTICS IN PAP SMEARS, HPV INFECTION WERE CATEGORIZED INTO THE FOLLOWING TWO GROUPS: Classical (koilocytic) changes (CC) encountered in 30 women and non classical changes (NCC) encountered in 120 women. It was observed that 21 (70%) CC and 46 (38.3%) NCC of HPV infection were positive for HR-HPV16; however only 12 cases (10%) of NCC and two cases (6.6%) of CC were positive for LR-HPV 6/11. Majority (41.7%) of HPV positive cases were reported in the age group of 25 to 30 years and HPV positivity decreased with the increasing age. CONCLUSION: Classical cellular changes are not the only diagnostic features for HPV infection in Pap smear, non-classical diagnostic features also support the diagnosis of HPV infection and may be positive for HR-HPV16. PMID- 22090689 TI - Efficacy of oral brush cytology in the evaluation of the oral premalignant and malignant lesions. AB - OBJECTIVE: In the present study, oral brush cytology of premalignant and malignant lesions was performed using tooth brush. The cytopathological diagnosis of brush cytology was compared with that of punch biopsy. The reliability of oral brush cytology using tooth brush was assessed in terms of sensitivity and specificity. MATERIALS AND METHODS: A total of 67 patients, 32 premalignant lesions and other 35 frank oral carcinomas, were included in the study. All patients underwent oral brush cytology using a toothbrush followed by punch biopsy. Sensitivity, specificity, positive and negative predictive values were calculated. Cytopathology and histopathology of premalignant and malignant lesions were compared using Mann-Whitney U test. Inter- and intra-examiner reliability was calculated using Rank-correlation coefficient. RESULTS: Two in premalignant group and five in malignant group were marked insufficient. 18% of cases were false negatives. The sensitivity, specificity, positive predictive value and negative predictive value were 77%, 100%, 100% and 38%, respectively. Statistical analysis showed P>0.05, suggesting that there is no significant difference between histopathology and brush cytology in assessing both premalignant and malignant lesions. Inter- and intra-examiner reliability were 99.22% and 99.77%, respectively. CONCLUSION: Brush cytology using a tooth brush is reliable and can be easily performed with less cost and discomfort to the patient. It is useful in those situations when a patient refuses to have a biopsy performed or when medically compromised patients would be exposed to unnecessary surgical risks. It can be used for screening for suspicious oral lesions, and may have applications in resource-challenged areas. PMID- 22090690 TI - Cytological pattern of cervical Papanicolaou smear in eastern region of Saudi Arabia. AB - BACKGROUND: Cancer of the cervix has been considered as one of the preventable cancers. This study is the first published research addressing the screening of cancer of the cervix in the eastern region of Saudi Arabia. AIM: This study aims to detect the prevalence of abnormal epithelial changes and its types in the eastern region of Saudi Arabia. SETTINGS AND STUDY DESIGN: A retrospective study was designed to evaluate all previously conducted cervical smears examined at a secondary care maternity hospital in Saudi Arabia, during the period from 2003 to 2010. During this period, a total of 1171 smears were reported. MATERIALS AND METHODS: We analyzed the records of all patients who had undergone Papanicolaou (Pap) smear during this period. After data collection, all cases were recorded as per Bethesda nomenclature. RESULTS: A total of 624 (53.3%) abnormal Pap smears were found, with only 58 cases reported to have epithelial pathological diagnosis (SIL). They represented 4.95% of total taken smears. A majority of the SIL diagnoses in our population were ASCUS, representing 60% of SIL cases. The prevalence of squamous cervical carcinoma was 0.34%. CONCLUSION: The study has shown a relatively high prevalence of epithelial abnormalities in cervical smears in the studied population. The squamous cell carcinoma represented a higher than the overall prevalence compared to World Health Organization (WHO) factsheets about Saudi Arabia. The mean age of epithelial abnormalities and squamous cell carcinoma was in the reproductive years. PMID- 22090692 TI - Erratum: ERRATUM. AB - [This corrects the article on p. 88 in vol. 28, PMID: 21713156.]. PMID- 22090691 TI - Value of ultrasonography-guided fine needle aspiration cytology in the investigative sequence of hepatic lesions with an emphasis on hepatocellular carcinoma. AB - BACKGROUND: The evaluation and management of various hepatic lesions is a common clinical problem and their appropriate clinical management depends on accurate diagnoses. AIMS: To study the cytomorphological features of distinctive non neoplastic and neoplastic lesions of the liver and to evaluate the sensitivity, specificity and diagnostic accuracy of ultrasonography (USG)-guided fine needle aspiration cytology (FNAC) in the diagnosis of liver diseases. MATERIALS AND METHODS: Seventy-two patients with evidence of liver diseases underwent USG guided, percutaneous FNAC. Cytomorphological diagnoses were correlated with clinical, biochemical and radiological findings, histopathological diagnoses and follow-up information. RESULTS: The age of the patients ranged from eight months to 90 years with 48 males (66.67%) and 24 females (33.33%). Of the 72 cases, the cytological diagnosis was rendered in 71 patients and smears were inadequate for interpretation in one case. Neoplastic lesions (68.06%) were more common than non neoplastic lesions (30.56%). The majority of the neoplastic lesions were hepatocellular carcinomas (36.12%) followed by metastatic adenocarcinomas (19.45%). Among non-neoplastic lesions, cirrhosis was the commonest lesion (8.34%). The overall diagnostic accuracy of FNAC was 97.82% with a sensitivity and specificity of 96.87 and 100% respectively. CONCLUSION: USG-guided FNAC of the liver is a safe, simple, cost-effective and accurate method for cytological diagnosis of hepatic diffuse, focal/nodular and cystic lesions with good sensitivity and specificity. PMID- 22090693 TI - Investigating the value of fine needle aspiration cytology in thyroid cancer. AB - BACKGROUND: Current guidance recommends the use of fine needle aspiration cytology (FNAC) as an essential investigation in patients presenting with a thyroid lump. Current literature suggests that the sensitivity of FNAC in thyroid nodules ranges between 80-90%. However, only very few studies have looked specifically at the sensitivity of FNAC in solely thyroid cancer patients. AIMS: The aim of our study was to investigate the value of FNAC as a first-line investigation in patients with thyroid cancer. We aimed specifically to assess the sensitivity of FNAC within this group. MATERIALS AND METHODS: Patients diagnosed with thyroid cancer between 2000-08 were identified from a local histopathology database. Sixty-seven case notes were retrieved, retrospectively reviewed and analyzed. Analysis included results of FNAC, ultrasound scanning and final histopathological diagnosis. RESULTS: Analysis of the 56 patients who underwent FNAC revealed that a cytological grading of thy3 or greater was only given to 31 cases (55.3%). CONCLUSION: In this study, FNAC findings of thy3 or greater were reported only in 55.3% of proven thyroid cancer cases. This study highlights the greater diagnostic difficulties of thyroid cancer compared to other thyroid nodules. Our findings suggest that clinicians must interpret the results of this initial investigation with caution and consider the routine use of ultrasound scanning to help guide FNAC. PMID- 22090694 TI - Role of argyrophilic nucleolar organizer region staining in identification of malignant cells in effusion. AB - BACKGROUND: Cytological examination of effusions helps to differentiate between benign and malignant effusions, but fails a definitive diagnosis in a number of cases. The main problem here is to distinguish reactive mesothelial cells from neoplastic cells. AIM: In the present study, we used argyrophilic nucleolar organizer region (AgNOR) staining for diagnosis of benign and malignant effusions. MATERIALS AND METHODS: In this study, 100 cases of effusion samples were taken and centrifuged. Four smears were prepared from sediment, one each for Leishman, hematoxylin and eosin (H and E) staining and two for AgNOR staining. AgNORs were counted as black dots in the nuclei of all abnormal cells using *100 oil immersion objective. Their dispersion and shape was compared in benign, malignant and atypical cases. RESULTS: Out of 50 pleural effusion samples, 29 were benign, 10 were malignant and 11 atypical. Among the 47 peritoneal effusion samples, 27 were benign, 16 were malignant and 4 atypical. Out of three cases of pericardial effusion samples, one was benign and two were malignant. All effusions were subjected to AgNOR staining. The benign group consisted of cells showing 1 to 2 dots of regular size and shape. In malignant group, 3 to 5 dots of variable size, shape and irregular contours were observed per cell. In atypical group, the reactive mesothelial cells showed 1 to 2 dots, malignant cells showed 3 to 4 irregular dots. Thus, a differentiation was noted between activated mesothelial cells and malignant cells, which was not possible in Leishman and H and E-stained smears alone. CONCLUSION: Therefore, AgNOR can be branded as an extremely useful additional diagnostic tool for cytodiagnosis of effusions. PMID- 22090695 TI - A cytomorphological study of secretions in breast cancer. AB - BACKGROUND: Secretions are seen in a range of breast cancer that includes invasive ductal carcinoma, mucinous carcinoma and secretory carcinoma. Evaluation of the quantity and location of secretions and the contours of the cell clusters complement cell morphology could improve diagnostic cytopathological criteria. AIM: To identify the range of breast carcinomas with secretions on fine-needle aspiration. MATERIALS AND METHODS: A retrospective study of 160 patients with breast carcinoma was carried out. The tumors were typed by evaluating the quantity and location of secretions, cellularity and nuclear grade. RESULTS: Secretions were seen in 16 of 160 breast carcinomas. Eleven were invasive ductal carcinoma (IDC), three were mucinous and two were secretory carcinomas. In IDC, minimal intracytoplasmic secretions were seen in 10, nuclear grades of 2 and 3 in 9, cell clusters with irregular margins in 6, and necrosis in 4. All mucinous and secretory carcinomas were nuclear grade 1. Extensive extracellular secretions and cell clusters with rounded contours were seen in mucinous carcinomas. In secretory carcinomas, the secretions were predominantly intracellular; stringy vasculature was a unique feature. CONCLUSION: Secretions in breast cancer are seen in a range of lesions that include IDC, mucinous, and secretory carcinomas. The quantity and location of secretions in breast cancer offer clues to differentiating these. PMID- 22090696 TI - Cytodiagnosis of intracranial metastatic adenoid cystic carcinoma: Spread from a primary tumor in the lacrimal gland. AB - Adenoid cystic carcinoma (ACC) of the lacrimal gland is a rarely encountered orbital tumor. It invades intracranially more frequently than carcinomas of other glands in the head and neck. A 61-year-old man underwent right orbital exenteration for a tumor in the supraorbital region. He had lost all records and presented to us with a diffuse swelling in the right forehead, six years later. Fine-needle aspiration cytology of the right frontal swelling revealed monomorphic population of small, slightly atypical cells, arranged in multilayered groups with abundant fine intercellular metachromatic substance between cell groups. There were hyaline globules of varying size with attached tumor cells. Cytological diagnosis of metastatic intracranial ACC with a lacrimal gland primary was suggested. Biopsy of the swelling confirmed our cytological diagnosis of ACC with perineural, vascular and lymphatic invasion. Thus, the authors report this case of intracranial metastasis of ACC of the lacrimal gland to remind neurosurgeons planning intervention that this disease shows a tendency to invade intracranially. PMID- 22090697 TI - Basal cell adenocarcinoma of submandibular salivary gland-problems in cytologic diagnosis. AB - Basal-cell adenoma and basal-cell adenocarcinoma of the salivary gland are rare tumors. Fine-needle aspiration cytology of these tumors, particularly those of basal-cell adenocarcinoma, has rarely been described in the literature. In this report, we describe the clinical, cytomorphologic and histopathologic features of basal cell adenocarcinoma in a 48-year-old male patient. Fine-needle aspiration specimen showed abundant cohesive groups of basaloid cells revealing focal anisonucleosis and nuclear atypia. The tumor cells also showed rosette-like arrangement around central eosinophilic globule. Pertinent literature is reviewed and differential diagnosis are discussed. PMID- 22090698 TI - Intraoperative scrape cytology: Adult granulosa cell tumor of ovary. AB - Adult granulosa cell tumor is often a hormonally active stromal cell neoplasm of the ovary with malignant potential. Intra-operative pathological assessment is a valuable tool in guiding optimal surgical treatment in patients. Of the various intra-operative cytological diagnostic modalities, scrape smear cytology is an effective, economical, simple, fast and reliable method with results comparable with frozen section diagnosis. We describe a case of adult granulosa cell tumor in a 30-years-old lady diagnosed on intra-operative scrape cytology, and further reconfirmed on frozen section and histopathology. PMID- 22090699 TI - Fine needle aspiration cytology of Hashimoto's thyroiditis - A diagnostic pitfall with review of literature. AB - Hashimoto's thyroiditis is the second most common thyroid lesion next to goiter diagnosed on fine needle aspiration cytology (FNAC). It is also an important cause for hypothyroidism. FNAC plays a significant role in the diagnosis of thyroid lesions due to its simplicity and low cost. It can accurately diagnose Hashimoto's thyroidits in most patients. However, a small percentage of cases may be missed due to the inherent limitations of this procedure and the varied cytomorphology of this lesion. Therefore thorough cytological evaluation and an integrated approach are necessary to pick up correct diagnosis and to avoid unnecessary surgery. We present a 56-year-old female with solitary thyroid nodule diagnosed as Hurthle cell neoplasm on FNAC, but subsequent histopathological diagnosis following resection revealed Hashimoto's thyroiditis with marked Hurthle cell change. PMID- 22090700 TI - Primary umbilical endometriosis - Diagnosis by fine needle aspiration. AB - Primary (spontaneous) umbilical endometriosis is very rare with an estimated incidence of 0.5-1% of all patients with endometrial ectopia. Endometriosis is a common gynecological condition, the pelvis being the most common site of the disease. Extrapelvic site is less common and even more difficult to diagnose due to the extreme variability in presentation. A 38-year-old woman presented with a blackish nodule over the umbilicus of 3 years duration. Fine needle aspiration cytology of the lesion showed cells in clusters and sheets with background of scant stromal fragment, hemosiderin laden macrophages and RBCs, leading to a suggestion of umbilical endometriosis. Histopathological examination of the excised lesion confirmed the same. PMID- 22090701 TI - Juvenile xanthogranuloma-diagnostic challenge on fine-needle aspiration cytology. AB - Juvenile xanthogranuloma (JXG) is a rare cutaneous lesion with paucity of literature on its cytological features. We report one such case which on fine needle aspiration cytology yielded a mixed population of foamy histiocytes, multinucleated giant cells and variable admixture of lymphocytes and eosinophils causing diagnostic dilemma with other differentials, especially Langerhans cell histiocytosis. However, clinical correlation followed by histopathology confirmed the diagnosis. Hence, JXG has characteristic and diagnostic cytologic features. PMID- 22090702 TI - Intraoperative cytology of central neurocytoma mimicking oligodendroglioma. AB - Central neurocytomas (CNs) are uncommon tumors of the central nervous system. These tumors have a predilection for the lateral ventricles of young adults and are known to display characteristic neuroimaging and histomorphologic features. Typically, CNs are associated with a favorable outcome, although cases with more aggressive clinical course with recurrences are not unknown. Most descriptions of this tumor are available in the form of isolated histopathology-based case reports and small series. Cytology-based publications of CN are rare. Here, we report a case of CN in a 22-year-old girl. Intra-operative squash cytology and subsequent histopathology of the tumor simulated an oligodendroglioma and a clear cell ependydoma. Final confirmation was obtained on immunohistochemistry. This paper discusses the salient cytological, histomorphological and immunohistochemical features of CN that are useful in distinguishing from its mimickers. PMID- 22090703 TI - Parathyroid carcinoma uncovering the enigma: Case report and review of literature. AB - Parathyroid carcinoma is a very rare cause of primary hyperparathyroidism. Pre operative diagnosis remains a challenge. We report a case referred for a suspicious goiter with a poor general condition associated with hypercalcemia. Cytological findings attributed it to a possible parathyroid neoplasm that must be considered in the differential diagnosis of a nodular thyroid mass by the cytopathologist. Serum parathormone levels were correlated and the patient underwent surgery. Histopathology confirmed the diagnosis of parathyroid carcinoma. There can be a major pitfall, as it may appear indistinguishable from a benign adenoma. PMID- 22090704 TI - Pancreatic metastasis in a case of small cell lung carcinoma: Diagnostic role of fine-needle aspiration cytology and immunocytochemistry. AB - Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA) cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology. PMID- 22090706 TI - Anaplastic large cell lymphoma: The evolution continues. PMID- 22090705 TI - ALK-negative anaplastic large cell lymphoma mimicking a soft tissue sarcoma. AB - Anaplastic lymphoma kinase protein (ALK)-negative anaplastic large cell lymphoma (ALCL) has a vast morphologic spectrum and may mimic many other types of malignancies both cytologically and histologically. There are only a few published case reports/series describing the cytomorphologic features of ALCL on fine-needle aspiration (FNA) biopsy specimens. We describe a case of ALK-negative ALCL mimicking a high-grade soft tissue sarcoma of the thigh in a 62-year-old man. The characteristic morphologic findings on FNA and core biopsy along with the immunophenotypic profile are described and reviewed. The diagnosis of ALCL on FNA biopsy may be difficult, but can be done successfully with the use of ancillary tests. Therefore, it must be considered in the differential diagnosis of lesions with pleomorphism, anaplasia, and wreath-like or horseshoe-shaped nuclei to ensure that adequate material is obtained for ancillary studies. PMID- 22090707 TI - Nodular hidradenoma of male breast: Cytohistological correlation. AB - Nodular hidradenoma is an established entity as a skin adnexal tumor arising from eccrine sweat glands. A skin adnexal tumor located in the breast is unusual and is one of the differential diagnoses for subareolar breast nodules. With the exception of gynecomastia, other lesions of the male breast are not very common. The review of literature showed only 25 reported cases till date. The rarity of this neoplasm and failure to identify its morphologic features may lead to misdiagnosis. Being itself rare, cytological features of this lesion are hardly encountered in case reports. We report a case of an 18-year-old male who presented with a left breast lump and underwent fine needle aspiration and was diagnosed as having a benign skin adnexal tumor. Later it was confirmed by histopathology to be a nodular hidradenoma. PMID- 22090708 TI - Accuracy of references in Journal of Cytology. PMID- 22090709 TI - Microfilaria in thyroid aspirate - An unexpected finding. PMID- 22090710 TI - Chromosomal aberrations in hematological malignancies: A guide to the identification of novel oncogenes. PMID- 22090711 TI - Are mannose-binding lectin gene 2 (MBL2) polymorphisms and MBL deficiency associated with infections? PMID- 22090712 TI - Craniosynostosis genetics: The mystery unfolds. AB - Craniosynsostosis syndromes exhibit considerable phenotypic and genetic heterogeneity. Sagittal synostosis is common form of isolated craniosynostosis. The sutures involved, the shape of the skull and associated malformations give a clue to the specific diagnosis. Crouzon syndrome is one of the most common of the craniosynostosis syndromes. Apert syndrome accounts for 4.5% of all craniosynostoses and is one of the most serious of these syndromes. Most syndromic craniosynostosis require multidisciplinary management. The following review provides a brief appraisal of the various genes involved in craniosynostosis syndromes, and an approach to diagnosis and genetic counseling. PMID- 22090713 TI - Characterization of cryptic rearrangements, deletion, complex variants of PML, RARA in acute promyelocytic leukemia. AB - Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation t(15;17)(q22;q21) leading to the disruption of Promyelocytic leukemia (PML) and Retionic Acid Receptor Alpha (RARA) followed by reciprocal PML-RARA fusion in 90% of the cases. Fluorescence in situ hybridization (FISH) has overcome the hurdles of unavailability of abnormal and/or lack of metaphase cells, and detection of cryptic, submicroscopic rearrangements. In the present study, besides diagnostic approach we sought to analyze these cases for identification and characterization of cryptic rearrangements, deletion variants and unknown RARA translocation variants by application of D-FISH and RARA break-apart probe strategy on interphase and metaphase cells in a large series of 200 cases of APL. Forty cases (20%) had atypical PML-RARA and/or RARA variants. D-FISH with PML/RARA probe helped identification of RARA insertion to PML. By application of D-FISH on metaphase cells, we documented that translocation of 15 to 17 leads to 17q deletion which results in loss of reciprocal fusion and/or residual RARA on der(17). Among the complex variants of t(15;17), PML-RARA fusion followed by residual RARA insertion closed to PML-RARA on der(15) was unique and unusual. FISH with break-apart RARA probe on metaphase cells was found to be a very efficient strategy to detect unknown RARA variant translocations like t(11;17)(q23;q21), t(11;17)(q13;q21) and t(2;17)(p21;q21). These findings proved that D-FISH and break-apart probe strategy has potential to detect primary as well as secondary additional aberrations of PML, RARA and other additional loci. The long-term clinical follow-up is essential to evaluate the clinical importance of these findings. PMID- 22090714 TI - The first report described as an important study: The association of mannose binding lectin gene 2 polymorphisms in children with Down syndrome. AB - BACKGROUND: Mannose-binding lectin gene 2 (MBL2) plays a very important role in the first line of host immune response in Down syndrome (DS). The importance of MBL2 gene polymorphisms in children with DS is unclear, and no research has addressed MBL2 gene polymorphisms in patients with DS. This is the first report describing an important association between MBL2 gene polymorphisms and infections in children with DS. MATERIALS AND METHODS: We compared the frequency of single-nucleotide polymorphisms (SNPs) at two codons of the MBL2 gene in a cross sectional cohort of 166 children with DS and 229 controls. Polymorphisms at codons 54 (GGC->GAC) and 57 (GGA->GAA) in exon 1 of the MBL2 gene were typed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique using the restriction enzymes BshN1 (derivated from Bacillus sphaericus) and MboII (derivated from Moraxella bovis), respectively. RESULTS: MBL2 codon 54 GA genotype frequency was found to be lower in patients with DS (22.9%) than those of healthy controls (35.8%), differences were statistically significant (OR = 0.532, 95% CI = 0.339-0.836, P = 0.008). On the other hand, codon 57 polymorphism in the MBL2 gene was detected in none of the DS patients, but only one person in the control group showed codon 57 GA genotype (OR = 1.004, 95% CI = 0.996-1.013, P = 1.000). CONCLUSION: Our data provides an evidence for the first time that a homozygote or heterozygote for the variant, MBL2 alleles, is not associated with infections in patients with DS, and do not influence the incidence of infections. PMID- 22090715 TI - Molecular investigation of mental retardation locus gene PRSS12 by linkage analysis. AB - The present study was carried out to determine the prevalence of families having mental retardation in Pakistani population. We enrolled seven mentally retarded (MR) families with two or more affected individuals. Family history was taken to minimize the chances of other abnormalities. Pedigrees were drawn using the Cyrillic software (version 2.1). The structure of pedigrees shows that all the marriages are consanguineous and the families have recessive mode of inheritance. All the families were studied by linkage analysis to mental retardation locus (MRT1)/gene PRSS12. Three STR markers (D4S191, D4S2392, and D4S3024) in vicinity of mental retardation (MR) locus (MRT1)/gene PRSS12 were amplified on all the sample of each family by PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE). The Haplotype were constructed to determine the pattern of inheritance and also to determine that a family was linked or unlinked to gene PRSS12. One out of the seven families was potentially linked to gene PRSS12, while the other six families remain unlinked. PMID- 22090716 TI - Novel mutations in arrhythmogenic right ventricular cardiomyopathy from Indian population. AB - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive condition with right ventricular myocardium being replaced by fibro fatty tissue. The spectrum of the expression may range from benign palpitations to the most malignant sudden death. Most of the mutations identified for the condition are localized in desmosomal proteins although three other nondesmosomal genes (cardiac ryanodine receptor-2, TGF-beta3, and TMEM43) have also been implicated in ARVC. Both desmosomal and nondesmosomal genes were screened in a set of patients from local population. MATERIALS AND METHODS: A set of 34 patients from local population were included in this study. Diagnosis was based on the criteria proposed by task force of European Society of Cardiology/International Society and Federation of Cardiology. Polymerase chain reaction-based single-strand conformation polymorphism analysis was carried out, and samples with abnormal band pattern were commercially sequenced. RESULTS: Screening of cardiac ryanodine receptor revealed an insertion of a base in the intronic region of exon-28 in a patient, leading to a creation of a cryptic splice site. Screening of plakohilin-2 for mutations revealed an abnormal band pattern in three patients. Two of them had similar abnormal band pattern for exon 3.1. Sequencing revealed a novel 2 base pair deletion (433_434 delCT), which would lead to premature truncation of the protein (L145EfsX8). Another patient showed abnormal band pattern for exon-3.2 and sequencing revealed a missense mutation C792T leading to amino acid change P244L, in N-terminal, and this substitution may cause disturbances in the various protein-protein interactions. CONCLUSION: This study reports novel cardiac ryanodine receptor (RyR-2) mutations and Pkp-2 for the first time from Indian population. PMID- 22090717 TI - Cytoprotective effect of honey against chromosomal breakage in fanconi anemia patients in vitro. AB - BACKGROUND: Natural honey is widely used all over the world as a complementary and alternative medicine in various disorders including Fanconi anemia (FA). FA is a rare genetic chromosomal instability syndrome caused by impairment of DNA repair and reactive oxygen species (ROS) imbalance. This disease is also related to bone marrow failure and cancer. The aim of this study was to evaluate the cytoprotective effect of honey on mitomycin C (MMC-) induced chromosomal damage in peripheral lymphocytes from FA patients. MATERIALS AND METHODS: Treatment of these complications with alkylation agents MMC may enhance chromosomal breakage. We have evaluated the effect of honey on MMC- induced chromosomal breakage in FA blood cells using chromosomal breakage assay. The basal chromosomal breakage count was higher among FA patients than healthy subjects. RESULTS: The addition of MMC alone gave a significantly higher of chromosomal breakage in FA patients than control group (P < 0.0001). Pre- treatment with honey significantly inhibited breakage induced by MMC in FA patients by its antioxidant effect. CONCLUSION: Honey can prevent MMC- induced chromosomal breakage by its antioxidant effect. PMID- 22090718 TI - Chromosomal abnormalities as a cause of recurrent abortions in Egypt. AB - BACKGROUND: In 4%-8% of couples with recurrent abortion, at least one of the partners has chromosomal abnormality. Most spontaneous miscarriages which happen in the first and second trimesters are caused by chromosomal abnormalities. These chromosomal abnormalities may be either numerical or structural. MATERIAL AND METHODS: Cytogenetic study was done for 73 Egyptian couples who presented with recurrent abortion at Genetic Unit of Children Hospital, Mansoura University. RESULTS: We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. Chromosomal abnormalities were detected in 9 (6.1%) of 73 couples. Seven of chromosomal abnormalities were structural and two of them were numerical. CONCLUSION: Our results showed that 6.1% of the couples with recurrent abortion had chromosomal abnormalities, with no other abnormalities. We suggest that it is necessary to perform cytogenetic in vestigation for couples who have recurrent abortion. PMID- 22090719 TI - Association of cytotoxic T lymphocyte-associated antigen 4 gene single nucleotide polymorphism with type 1 diabetes mellitus in Madurai population of Southern India. AB - Type 1 diabetes mellitus formerly called juvenile diabetes, is an organ specific T-cell mediated autoimmune disease characterized by the progressive loss of function of the insulin producing beta-cells of the islets of Langerhans. Cytotoxic T lymphocyte-associated antigen 4 gene (CTLA-4) has been proposed as a candidate gene for conferring susceptibility to autoimmunity. Association of CTLA 4 gene polymorphism is well established in autoimmune endocrinopathies across world population. The present study was conducted to investigate the association of CTLA-4 exon 1 49A/G polymorphism with TIDM in Madurai, a city in Southern India. Fifty three clinically proven T1DM patients and 53 control subjects with no history of autoimmune disease were recruited for the study. Genomic DNA was extracted from peripheral blood. CTLA-4 exon 1 49 A/G polymorphism was assessed using PCR-RFLP methods. Our findings revealed a significant association of CTLA-4 exon 1 49 A/G polymorphism with T1DM in Madurai population. PMID- 22090720 TI - G-C heterozygosis in mutS homolog2 as a risk factor to hereditary nonpolyposis colon cancer in the absence of a family medical history. AB - To detect the presence of point mutations in a small section of the mutS homolog2 (MSH2) gene in both healthy and affected persons treated at the General Hospital of the State of Sonora, a 353 base pair section of the MSH2 gene was amplified and sequenced from six persons affected by hereditary nonpolyposis colorectal cancer and from 19 healthy persons. The affected persons did not show the mutations reported in the scientific literature; however, six healthy persons were heterozygote and mutant-allele carriers. The heterozygote condition implies that carriers are candidates for the development of colorectal cancer. However, it is important to know the family medical history when investigating hereditary mutations. PMID- 22090721 TI - McKusick-Kaufman or Bardet-Biedl syndrome? A new borderline case in an Italian nonconsanguineous healthy family. AB - McKusick-Kaufman syndrome (MKS, OMIM #236700) is a rare syndrome inherited in an autosomal recessive pattern with a phenotypic triad comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP), and congenital cardiac disease (CHD). The syndrome is caused by mutations in the MKKS gene mapped onto chromosome 20p12 between D20S162 and D20S894 markers. Mutations in the same gene causes Bardet Biedl-6 syndrome (BBS-6, OMIM #209900) inherited in an autosomal recessive pattern. BBS-6 comprises retinitis pigmentosa, polydactyly, obesity, mental retardation, renal and genital anomalies. HMC, CHD, and PAP defects can also occur in BBS-6, and there is a significant clinical overlap between MKS and BBS-6 in childhood. We describe a new borderline case of MKS and BBS syndrome and suggest insights for understanding correlation between MKKS gene mutations and clinical phenotype. Here, we report the results of molecular analysis of MKKS in a female proband born in an Italian nonconsanguineous healthy family that presents HMC and PAP. The mutational screening revealed the presence of two different heterozygous missense variants (p.242A>S in exon 3, p.339 I>V in exon 4) in the MKKS gene, and a nucleotide variation in 5'UTR region in exon 2 (-417 A>C). PMID- 22090722 TI - A recurrent mutation in Moroccan patients with Dyggve-Melchior-Clausen syndrome: Report of a new case and review. AB - Dyggve-Melchior-Clausen (DMC) syndrome is a rare autosomal recessive disorder. It is a spondyloepimetaphyseal dysplasia associated with mental retardation. Clinical manifestations include coarse facies, microcephaly, short trunk dwarfism, and mental retardation. Mutations in Dymeclin gene (DYM), mapped to chromosome 18q21.1, is responsible for DMC. We report here the observation of a consanguineous Moroccan patient having DMC syndrome. The molecular studies showed a previously reported homozygous mutation at c.1878delA of DYM gene. We discuss this recurrent mutation in Moroccan patients with DMC syndrome with a review. PMID- 22090723 TI - Deletion of ABL/BCR on der(9) associated with severe basophilia. AB - Chronic basophilic leukemia is a rare form in chronic myeloid leukemia patients. Only limited number of reports are available. Herein, we describe a patient who presented with fatigue, weight loss, leucocytosis, prominent basophilia, and mild eosinophilia. On biopsy, bone marrow was hypercellular with marked basophils. The immunophenotype showed abnormal expression of CD7, which is suggestive of basophilic maturation. Chromosomal analysis from GTG-banded metaphases revealed Ph positivity, and fluorescence in situ hybridization (FISH) with BCR/ABL dual color, dual fusion probe showed single fusion on the der(22) chromosome and ABL/BCR fusion was deleted on the der(9) chromosome. The deletion (ABL/BCR) on der(9) may be associated with basophilia which may be also indicative of the transformation of CML to acute myeloid leukemia. PMID- 22090724 TI - Congenital erythropoietic porphyria with two mutations of the uroporphyrinogen III synthase gene (Cys73Arg, Thr228Met). AB - Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase (UROS). We describe a 14-year-old girl with red urine since infancy, progressive blistering and scarring of the skin, and moderate hemolytic anemia. After years of skin damage, her face is mutilated; she has a bald patch on the scalp, hypertrichosis of the neck, areas of skin darkening, and limited joint movements of the hands. Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. Sequencing of the UROS gene identified two mutations causing CEP (Cys73Arg, Thr228Met). The patient lesions are progressing. Bone marrow transplantation and/or gene therapy are proposed as the next steps in her treatment. In brief, we describe a CEP with confirmed two pathogenic mutations, severe phenotype and discuss the various treatment options available. PMID- 22090725 TI - Early recurrent left atrial myxoma in a teenager with de novo mutation of Carney complex. AB - We report a case of an extremely early recurrence of left atrial myxoma in a 13 year-old girl. On hospital admission, the clinical presentation was of cerebral embolism with noticeable spotty skin pigmentation and hypertelorism. The left atrial myxoma originated from the roof of the left atrium. The histology specimen showed typical finding of a myxoma. Six months later a new intracardial mass was evacuated, the postoperative result showing the same type of myxomatous tissue. Genetic investigations demonstrated Carney complex. The genetic analysis of the child's family was negative, demonstrating de novo mutation of this rare disorder. PMID- 22090726 TI - Prenatal diagnosis in a mentally retarded woman with mosaic ring chromosome 18. AB - We present a pregnant woman with mental retardation and mosaic for ring 18 referred for prenatal diagnosis. Major clinical features included short stature with clinodactyly in feet, foot deformity and club feet, hypotonia, kyphosis, and absence of breast development, low set ears, high arched palate, dental decay and speech disorder. Prenatal diagnosis was carried. Using amniocentesis. The fetus had a normal karyotype described as 46,XX. The fetus was evaluated for clinical features after delivery; she was healthy with no abnormal clinical characterizations. PMID- 22090727 TI - Transcoronary ethanol ablation for ventricular tachycardia. PMID- 22090728 TI - Autonomic denervation for the treatment of atrial fibrillation. AB - The influence of the autonomic nervous system (ANS) on triggering and perpetuation of atrial fibrillation (AF) is well established. Ganglionated plexi (GP) ablation achieves autonomic denervation by affecting both the parasympathetic and sympathetic components of the ANS. An anatomic approach for GP ablation at relevant atrial sites appears to be safe, and improves the results of PV isolation in patients with paroxysmal and persistent AF. GP ablation can be accomplished endocardially or epicardially, ie, during the maze procedure or thoracoscopic approaches. Further experience is needed to assess the clinical value of this promising technique. PMID- 22090729 TI - Entrainment during Ablation of Ischemic Ventricular Tachycardia. What is explanation for Post Pacing Interval shorter than the tachycardia cycle length? AB - Entrainment mapping of ischemic ventricular tachycardia at a site in the left ventricle where radiofrequency ablation was successful in terminating the tachycardia revealed a post-pacing interval shorter than the tachycardia cycle length. The reason for the same is explained in the current report. PMID- 22090730 TI - An unusual mechanism of sustained right atrial tachycardia. AB - Lower loop re-entry (LLR) flutter is a rare type of atypical right atrial flutter. Most of the reported cases occurred in association with typical flutter patterns as a transient arrhythmia. Our case is unique in the fact the LLR was sustained and persisted independently. PMID- 22090731 TI - Spontaneous demonstration of counterclockwise right atrial activation following successful isthmus ablation. AB - We describe an uncommon case of typical flutter with symptomatic sinus node dysfunction, in which a permanent junctional rhythm developed following ablation of the cavo-tricuspid isthmus. This rhythm activated the right atrium in counter clockwise manner thus providing spontaneous proof of unidirectional isthmus block, a phenomenon that is usually demonstrated by proximal coronary sinus pacing. PMID- 22090732 TI - Placement Of A Coronary Sinus Pacing Lead From A Sub-occluded Left Subclavian Vein Using A Collateral Vein To The Right Subclavian Vein. AB - Upgrading of a pacing system in the presence of a subclavian occlusion is technically challenging. We describe the case of a patient who underwent a successful upgrading procedure of an implantable cardioverter-defibrillator (ICD) to a biventricular defibrillator (ICD-CRT) in the presence of a suboccluded left subclavian vein, using a collateral vein that drained into the contralateral subclavian vein. PMID- 22090733 TI - What's New in Emergencies, Trauma and Shock ? Optimizing initial resuscitation strategies in a patient with shock. PMID- 22090734 TI - Diagnostic accuracy of bedside emergency ultrasound screening for fractures in pediatric trauma patients. AB - BACKGROUND: Bedside ultrasound (BUS) can effectively identify fractures in the emergency department (ED). AIM: To assess the diagnostic accuracy of BUS for fractures in pediatric trauma patients. SETTING AND DESIGN: Prospective observational study conducted in the ED. MATERIAL AND METHODS: Pediatric patients with upper and lower limb injuries requiring radiological examination were included. BUS examinations were done by emergency physicians who had undergone a brief training. X-rays were reviewed for the presence of fracture and the results of BUS and radiography were compared. STATISTICAL ANALYSIS: STATA version 11 was used for statistical analysis of the data. RESULTS: Forty-one patients were enrolled in the study. The sensitivity of the BUS in detecting fracture was 89% [95% confidence interval (CI): 51% to 99%] and the specificity was 100% (95% CI: 87% to 100%). The positive predictive value of BUS was 100% and negative predictive value was 97%. CONCLUSION: BUS can be utilized by emergency physicians after brief training to accurately identify long bone fractures in the pediatric age-group. PMID- 22090735 TI - Evaluation of trauma and prediction of outcome using TRISS method. AB - INTRODUCTION: Trauma and injury severity score (TRISS), introduced in 1981 is a combination index based on revised trauma score (RTS), injury severity score (ISS) and patient's age. In this study we have used TRISS method to predict the outcome in trauma cases. MATERIALS AND METHODS: 1000 consecutive cases of trauma of adult age group admitted in casualty of Dayanand Medical College and Hospital Ludhiana, from 1/7/2000 onwards. Revised Trauma Score, Injury Severity Score and Age Index were recorded from which TRISS was determined. The performance of TS, ISS and TRISS as predictors of survival was evaluated using the misclassification rate, the information gain and the relative information gain. RESULTS: The majority of the patients were men (83.7%) and in the age group of 20-50 years. Road traffic collisions (72%) were the most common cause of trauma. The mortality rate was 4.1%. Using PER method, the TRISS method was found to have information gain of 0.049 and a relative information gain of 0.41. CONCLUSIONS: The revised trauma score (RTS) ranged from 2.746 to 7.8408.There was a graded increase in mortality with decreasing RTS score. PMID- 22090736 TI - Damage control in severely injured trauma patients - A ten-year experience. AB - BACKGROUND: This study reviews our 10-year institutional experience with damage control management and investigates risk factors for early mortality. MATERIALS AND METHODS: The trauma registry of our level I trauma centre was utilized to identify all patients from 01/96 through 12/05 who underwent initial damage control procedures. Demographics, clinical and physiological parameters, and outcomes were abstracted. Patients were categorized as either early survivors (surviving the first 72 hours after admission) or early deaths. RESULTS: During the study period, 319 patients underwent damage control management. Overall, 52 patients (16.3%) died (early deaths) and 267 patients (83.7%) survived the first 72 hours (early survivors). Early deaths showed significantly deranged serum lactate (5.81+/-0.55 vs. 3.46+/-0.13 mmol/L; P<0.001), base deficit (10.10+/-0.95 vs. 4.90+/-0.28 mmol/L; P<0.001) and pH (7.16+/-0.03 vs. 7.29+/-0.01; P<0.001) levels compared to early survivors on hospital admission. An International Normalized Ratio >1.2, base deficit >3 mmol/L, head Abbreviated Injury Scale >=3, body temperature <35 degrees C, serum lactate >6 mmol/L, and hemoglobin <7 g/dL proved to be independent risk factors for early mortality on hospital admission. CONCLUSIONS: Several risk factors for early mortality such as severe head injury and the lethal triad (coagulopathy, acidosis and hypothermia) in patients undergoing damage control procedures were identified and should trigger the trauma surgeon to maintain aggressive resuscitation in the intensive care unit. PMID- 22090737 TI - Changing trends in the pattern and outcome of stab injuries at a North London hospital. AB - OBJECTIVE: To study the incidence, pattern and outcome of stab injuries attending a North London Teaching Hospital over a 3-year (2006-2008) period. MATERIALS AND METHODS: A retrospective review of collected data from the Hospital database was conducted. The database contains comprehensive medical records for all patients attended by the trauma team for deliberate stab injuries. It is updated by the surgical team after each admission. All patients with deliberate penetrating injury who were attended by the service between 1 January 2006 and 31 December 2008 were identified. Patients who died in the prehospital phase, those managed exclusively by the emergency department and limb injuries without vascular compromise were excluded from the study. RESULTS: Six hundred and nineteen patients with stab injuries (following knife crime) from North London attended the Hospital in the above period. One hundred and thirty-seven paients required surgical admission. Two were cases of self-inflicted knife injuries. Over the 3 year period the percentage of victims below 20 years of age is increasing. Ninety three percent of knife crime occured between 6 pm and 6 am; recently moving toward week days from weekend period. CONCLUSIONS: The overall rate of penetrating injuries (stab injuries) is slowly declining. Timely cardiothoracic support facility is vital in saving lives with major cardiac stab injuries. Although alcohol drinking restriction has been lifted, most cases of stabbings are still occurring out-of-hours when surgical personnel are limited. PMID- 22090738 TI - Diagnostic accuracy of preoperative clinical examination in upper limb injuries. AB - BACKGROUND: Injuries in hands and forearms may cause significant discomfort and disability. AIM: To evaluate the accuracy of preoperative clinical examination in depicting lesions caused by penetrating wounds of hands or forearms. SETTING AND DESIGN: This prospective study was conducted from August 2006 to September 2009 at Kashani University Hospital, Isfahan University of Medical Sciences, Iran. MATERIALS AND METHODS: Two hundred and fifty patients with clean penetrating injury to the hand/forearm were enrolled in this study. After patient's data registration, a careful clinical examination and routine exploration without expansion of wound were done by an orthopedic resident. Each tendon was tested at each joint level. Nerves were evaluated with a two-point discrimination test, and arteries were tested with palpable pulses. Surgical exploration was done by a single hand surgeon in operation room. Accuracy of clinical examination was compared to surgical examination. RESULTS: During the study period, 180 (72%) males and 70 (28%) females with mean age of 28+/-4 years participated. The preoperative examination showed a predominance of the volar zone IV injuries followed by volar zone II, III, thumb zone II, volar zone V and thumb zone III. Despite the enough accuracy of preoperative examinations in dorsal side injuries of hands and forearms (error rate = 8.3%), the preoperative examinations significantly underestimated the amount of damage to soft tissues on the volar side of hands and forearms (error rate = 14%). CONCLUSIONS: The precise surgical evaluations should be considered in patients with penetrating injury to the hand or forearm, especially in those with volar side injuries. PMID- 22090739 TI - Influence of prehospital fluid resuscitation on patients with multiple injuries in hemorrhagic shock in patients from the DGU trauma registry. AB - BACKGROUND: Severe bleeding as a result of trauma frequently leads to poor outcome by means of direct or delayed mechanisms. Prehospital fluid therapy is still regarded as the main option of primary treatment in many rescue situations. Our study aimed to assess the influence of prehospital fluid replacement on the posttraumatic course of severely injured patients in a retrospective analysis of matched pairs. MATERIALS AND METHODS: We reviewed data from 35,664 patients recorded in the Trauma Registry of the German Society for Trauma Surgery (DGU). The following patients were selected: patients having an Injury Severity Score >16 points, who were >=16 years of age, with trauma, excluding those with craniocerebral injuries, who were admitted directly to the participating hospitals from the accident site. All patients had recorded values for replaced volume and blood pressure, hemoglobin concentration, and units of packed red blood cells given. The patients were matched based on similar blood pressure characteristics, age groups, and type of accident to create pairs. Pairs were subdivided into two groups based on the volumes infused prior to hospitalization: group 1: 0-1500 (low), group 2: >=2000 mL (high) volume. RESULTS: We identified 1351 pairs consistent with the inclusion criteria. Patients in group 2 received significantly more packed red blood cells (group 1: 6.9 units, group 2: 9.2 units; P=0.001), they had a significantly reduced capacity of blood coagulation (prothrombin ratio: group 1: 72%, group 2: 61.4%; P<=0.001), and a lower hemoglobin value on arrival at hospital (group 1: 10.6 mg/dL, group 2: 9.1 mg/dL; P<=0.001). The number of ICU-free days concerning the first 30 days after trauma was significantly higher in group 1 (group 1: 11.5 d, group 2: 10.1 d; P<=0.001). By comparison, the rate of sepsis was significantly lower in the first group (group 1: 13.8%, group 2: 18.6%; P=0.002); the same applies to organ failure (group 1: 36.0%, group 2: 39.2%; P<=0.001). CONCLUSION: The high amounts of intravenous fluid replacement was related to early traumatic coagulopathy, organ failure, and sepsis rate. PMID- 22090740 TI - Indications for brain computed tomography scan after minor head injury. AB - AIMS: Minor head injury (MHI) is a common injury seen in Emergency Departments (ED). Computed tomography (CT) scan of the brain is a good method of investigation to diagnose intracranial lesions, but there is a disagreement about indications in MHI patients. We surveyed the post-traumatic symptoms, signs or past historical matters that can be used for the indication of brain CT scan. MATERIALS AND METHODS: All patients with MHI who were older than 2 years, had a Glasgow Coma Scale (GCS) score >=13 and were referred to the ED, underwent brain CT scan. Data on age, headache, vomiting, loss of consciousness (LOC) or amnesia, post-traumatic seizure, physical evidence of trauma above the clavicles, alcohol intoxication, and anticoagulant usage were collected. The main outcome measure was the presence of lesions related to the trauma in brain CT scan. For categorical variables, Chi-square test was used. RESULTS: Six hundred and forty two patients were examined by brain CT scan after MHI, and 388 patients (60.4%) did not have any risk indicator. Twenty patients (3.1%) had abnormal brain CT scans. The logistic regression model showed that headache (P=0.006), LOC or amnesia (P=0.024) and alcohol (P=0.036) were associated with abnormal brain CT. CONCLUSIONS: WE SUGGESTED THAT ABNORMAL BRAIN CT SCAN RELATED TO THE TRAUMA AFTER MHI CAN BE PREDICTED BY THE PRESENCE OF ONE OR MORE OF THE FOLLOWING RISK INDICATORS: Headache, vomiting, LOC or amnesia, and alcohol intoxication. Thus, if any patient has these indicators following MHI, he must be considered as a high-risk MHI. PMID- 22090741 TI - C-clamp and pelvic packing for control of hemorrhage in patients with pelvic ring disruption. AB - BACKGROUND: Exsanguinating hemorrhage is the major cause of death in patients with pelvic ring disruption. AIMS: The aim of this study was to document outcomes after the stabilization of pelvic ring injuries by a C-clamp and control of hemorrhage by pelvic packing. Physiological parameters were tested as prognostic factors. SETTING AND DESIGN: This was a retrospective study at a level I trauma center. The study period was from January 1996 to December 2007. MATERIALS AND METHODS: Fifty patients with pelvic ring disruption and hemorrhagic shock were analyzed. The pelvic rings were fixed by a C-clamp, and patients with ongoing hemorrhage underwent laparotomy and extra- and/or intra-peritoneal pelvic packing. Clinical parameters (heart rate, mean arterial pressure) and physiological parameters (lactate levels, hemoglobin, hematocrit) were documented at admission and at different time points during the initial treatment (1, 2, 3, 4, 6, 8, and 12h after admission). RESULTS: Within 12 h of admission, 16 patients died (nonsurvivors) due to hemorrhagic shock (n=13) or head injuries (n=3). In this group, 12 patients underwent laparotomy with pelvic packing. Thirty-four patients survived the first 12 h (early survivors) after fixation by a C-clamp and additional packing in 23 patients. Four of these patients died 12.3+/-7.1 days later due to multiple organ failure (n=3) or severe head injury (n=1). The blood lactate level at admission was significantly higher in the group of nonsurvivors (7.2+/-0.8 mmol/L) compared to the early survivors (4.3+/-0.5 mmol/L, P<0.05). While hemoglobin values improved within the first 2 h in nonsurvivors, lactate levels continued to increase. CONCLUSION: Pelvic packing in addition to the C-clamp fixation effectively controls severe hemorrhage in patients with pelvic ring disruption. Early sequential measurements of blood lactate levels can be used to estimate the severity of shock and the response to the shock treatment. PMID- 22090742 TI - Evaluating a conservative approach to managing liver injuries in Kashmir, India. AB - AIM: There has been a steep rise in incidence of liver injury in the past few years because of increase in incidence of road traffic accidents. The aim of this study was to evaluate the role of non-operative management of liver injury due to blunt abdominal trauma. MATERIALS AND METHODS: All patients with liver injury from blunt trauma abdomen were studied between January 2000 and January 2010. A total of 152 patients with liver injury were put on conservative management. Hundred and three (67.77%) patients were males and 49 (32.23%) were females with an age range of 15-60 years (32.8 years). Most of the injuries were because of road traffic accidents (81.57%). Liver injuries were graded according to Moore's classification using computed tomography. Patients with Grade V and VI were excluded from the study. Patients who were unstable hemodynamically on admission were also excluded from the study. RESULTS: There was no mortality in our series. Eight patients needed exploration because they developed hemodynamic instability. Four of the patient developed post-operative liver abscess which was treated conservatively. CONCLUSION: Non-operative management of liver injury due to blunt trauma abdomen is a safe, effective and treatment modality of choice in hemodynamically stable Moore's grade I to Grade IV injury. PMID- 22090743 TI - The provision of critical care in emergency departments at Canada. AB - INTRODUCTION: Critically ill patients are common in emergency medicine, and require expert care to maximize patient outcomes. However, little data is available on the provision of critical care in the ED. The goal of this study is to describe the management of critically ill patients in the ED via a survey of Canadian emergency physicians. MATERIALS AND METHODS: A survey of attending physician members of CAEP was conducted by email. The survey was developed by the authors and internal validity was established prior to survey deployment. Data on physician demographics, hospital resources, use of invasive procedures, vasopressor/inotropic medications, length of stay in the ED and patient responsibility were assessed. RESULTS: The survey response rate was 22.9%, with the majority of respondents possessing speciality training in EM (73.5%). Respondents indicated that critically ill patients were commonly managed in the ED, with 68.5% reporting >6 critically ill patients per month, and 12.4% indicating > 20 patients per month. Respondents indicated that the majority of critically ill patients remained in the ED for 1-4 hours (70%) after resuscitation, yet 18% remained in the ED for >5 hours. Patients with a "respiratory" etiology were the most common critically ill patient population reported, followed by "cardiovascular", "infectious" and "traumatic illness". Direct laryngoscopy was frequently performed (66.9%> 11 in the year prior to the survey) in the year prior to the survey, while other invasive procedures and vasopressor/inotropic medications were utilized less often. EM physicians were responsible for the management of critically ill patients in the ED, even after consultation to an inpatient service, and were often required to provided acute care to critically ill patients admitted to an ICU, yet remaining in the ED prior to transfer (20% reported > 50% of the time). CONCLUSION: Our survey demonstrates that critically ill patients are common in Canadian ED's, and that EMP's are often responsible to provide care for prolonged period of time. In addition, the use of invasive procedures other then direct laryngoscopy was variable. Further research is warranted to determine the impact of delayed transfer and ED physician management of critically ill patients in the ED. PMID- 22090744 TI - Designing, managing and improving the operative and intensive care in polytrauma. AB - BACKGROUND AND CONTEXT: Polytrauma is a leading cause of mortality in the developing countries and efforts from various quarters are required to deal with this increasing menace. AIMS AND OBJECTIVES: An attempt has been made by the coordinated efforts of the intensive care and trauma team of a newly established tertiary care institute in designing and improving the trauma care services to realign its functions with national policies by analyzing the profile of polytrauma victims and successfully managing them. MATERIALS AND METHODS: A retrospective analysis was carried out among the 531 polytrauma admissions in the emergency department. The information pertaining to age and gender distribution, locality, time to trauma and initial resuscitation, cause of injury, type of injury, influence of alcohol, drug addiction, presenting clinical picture, Glasgow Coma score on admission and few other variables were also recorded. The indications for various operative interventions and intensive care unit (ICU) admissions were analyzed thoroughly with a concomitant improvement of our trauma care services and thereby augmenting the national policies and programs. A statistical analysis was carried out with chi-square and analysis of variance ANOVA tests, using SPSS software version 10.0 for windows. The value of P<0.05 was considered significant and P<0.0001 as highly significant. RESULTS: Majority of the 531 polytrauma patients hailed from rural areas (63.65%), riding on the two wheelers (38.23%), and predominantly comprised young adult males. Fractures of long bones and head injury was the most common injury pattern (37.85%) and 51.41% of the patients presented with shock and hemorrhage. Airway management and intubation became necessary in 42.93% of the patients, whereas 52.16% of the patients were operated within the first 6 hours of admission for various indications. ICU admission was required for 45.76% of the patients because of their deteriorating clinical condition, and overall,ionotropic support was administered in 55.93% of the patients for successful resuscitation. CONCLUSIONS: There is an urgent need for proper implementation ofpre-hospital and advanced trauma life support measures at grass-root level. Analyzing the profile of polytrauma victims at a national level and simultaneously improving the trauma care services at every health center are very essential to decrease the mortality and morbidity. The improvement can be augmented further by strengthening the rural health infrastructure, strict traffic rules, increasing public awareness and participation and coordination among the various public and private agencies in dealing with polytrauma. PMID- 22090745 TI - Clinical ultrasound physics. AB - Understanding the basic physics of ultrasound is essential for acute care physicians. Medical ultrasound machines generate and receive ultrasound waves. Brightness mode (B mode) is the basic mode that is usually used. Ultrasound waves are emitted from piezoelectric crystals of the ultrasound transducer. Depending on the acoustic impedance of different materials, which depends on their density, different grades of white and black images are produced. There are different methods that can control the quality of ultrasound waves including timing of ultrasound wave emission, frequency of waves, and size and curvature of the surface of the transducer. The received ultrasound signal can be amplified by increasing the gain. The operator should know sonographic artifacts which may distort the studied structures or even show unreal ones. The most common artifacts include shadow and enhancement artifacts, edge artifact, mirror artifact and reverberation artifact. PMID- 22090746 TI - The sonographic diagnosis of pneumothorax. AB - Ultrasound is a modality now available to all physicians and can help in making rapid decisions, particularly with critically ill patients. This article reviews the basis of the use of sonography for the diagnosis of pneumothorax. PMID- 22090747 TI - The role of ultrasound in life-threatening situations in pregnancy. AB - Pregnant women are at an increased risk of a number of conditions that are associated with bleeding. Conditions such as ectopic pregnancy, retained products of conception, placenta previa, abruptio placentae, morbid adhesion of the placenta, and postpartum hemorrhage can be associated with massive bleeding that endangers the maternal life and health. Screening, early detection, and prevention play a key role in reducing maternal morbidity and mortality caused by these conditions. Ultrasound, in experienced hands, is an effective tool that can assist in diagnosing many of these obstetrical conditions. The advances in technology and the non-invasive nature of ultrasound examination have made it popular in our daily obstetrical practice. The review discusses the role of ultrasound in the most common life-threatening conditions during pregnancy. PMID- 22090748 TI - Sonographic diagnosis of intraperitoneal free air. AB - Detection of intraperitoneal free air is important for the diagnosing of life threatening conditions in patients with acute abdominal pain. Point-of-care ultrasound is an extension of the clinical examination in patients presenting with acute abdomen. Failure of sonographers to detect intraperitoneal free air was clinically considered as a limitation of abdominal ultrasound. It is now increasingly appreciated that ultrasound may detect intraperitoneal free air. Emergency physicians should be familiar with the sonographic features of intraperitoneal free air which may be essential to recognize bowel perforation. Herein we review the literature on the sonographic findings of intraperitoneal free air and the technical manoeuvres that can improve clinicians' detection of intraperitoneal free air using point-of-care ultrasound. PMID- 22090749 TI - Duodenal perforation following blunt abdominal trauma. AB - Duodenal perforation following blunt abdominal trauma is an extremely rare and often overlooked injury leading to increased mortality and morbidity. We report two cases of isolated duodenal injury following blunt abdominal trauma and highlight the challenges associated with their management. In both these patients, the diagnosis of the duodenal injuries was delayed, leading to prolonged hospital stay. The first patient had two perforations, one on the anterior and the other on the posterior wall of the duodenum, of which the posterior perforation was missed at initial laparotomy. In the other patient, the duodenal injury was missed during the initial assessment in the emergency department. He returned to the emergency department 24 hours after discharge with abdominal pain and vomiting. During trauma related laparotomy, complete kocherization (mobilization) of the duodenum must be mandatory, even in the presence of obvious injury on its anterior wall. We emphasize on keeping the management protocol simple by a "triple tube decompression", i.e. duodenorrhaphy (simple closure), tube gastrostomy, reverse tube duodenostomy and a feeding jejunostomy. PMID- 22090750 TI - A large left atrial myxoma detected in emergency department using bedside transthoracic echocardiography. AB - We present a case of a 55-year-old woman with episodes of recurrent pulmonary edema that was diagnosed to have a large left atrial myxoma using bedside transthoracic echocardiography. This case illustrates the importance of a screening focused ultrasound examination of involved systems by emergency physicians in detecting causes for emergency clinical presentations. PMID- 22090751 TI - Ultrasound diagnosis of quadriceps tendon tear in an uncooperative patient. AB - A 38-year-old intoxicated man presented to the emergency department with a painful, swollen left knee and inability to ambulate after being tackled to the ground. The patient was uncooperative, and physical examination of the lower extremities was limited by his intoxication. Radiographic examination of the knee was unremarkable. Ultrasound of the knee revealed a quadriceps tendon rupture. The sonographic features of quadriceps tendon rupture are described, as is the role ultrasound plays in the assessment of a swollen, painful knee. PMID- 22090752 TI - Malposition of central venous catheter in a small tributary of left brachiocephalic vein. AB - Erroneous positioning of central venous catheters in small tributaries of large central veins is a rare occurrence. We describe two such unusual incidents involving cannulation of the small tributaries of left brachiocephalic vein. Malposition was suspected when the central venous waveform could not be obtained despite all attempts. Unusual central venous waveforms may indicate central venous catheter malposition, and these waveforms have not previously been described. PMID- 22090753 TI - Telementorable "just-in-time" lung ultrasound on an iPhone. PMID- 22090754 TI - Wonders of discovery. PMID- 22090755 TI - Secondary alveolar bone grafting in cleft of the lip and palate patients. AB - AIM: The aim was to restore the function and form of both arches with a proper occlusal relationship and eruption of tooth in the cleft area. MATERIALS AND METHODS: Eleven patients were selected irrespective of sex and socio-economic status and whose age was within the mixed dentition period. Iliac crest is grafted in cleft area and subsequently evaluated for graft success using study models, and periapical and occlusal radiographs. RESULTS: At the time of evaluation teeth were erupted in the area and good alveolar bone levels were present. Premaxilla becomes immobile with a good arch form and arch continuity. There are no major complications in terms of pain, infection, paraesthesia, hematoma formation at donor site without difficulty in walking. There is no complication in terms of pain, infection, exposure of graft, rejection of graft, and wound dehiscence at the recipient site. DISCUSSION: It is evident that secondary alveolar grafting during the mixed dentition period is more beneficial for patients at the donor site as well as the recipient site. CONCLUSION: Long term follow-up is required to achieve maximum advantage of secondary alveolar grafting; the age of the patient should be within the mixed dentition period, irrespective of sex, socio-economic status. It may be unilateral or bilateral. PMID- 22090756 TI - Shear bond strength of composite resin to dentin after application of cavity disinfectants - SEM study. AB - AIM: The aim was to evaluate the effect of different cavity disinfectants on dentin bond strengths of composite resin applied with two different adhesive systems. MATERIALS AND METHODS: Two-hundred mandibular molars were sectioned parallel to the occlusal surface to expose dentin in the midcoronal one-third. The dentinal surfaces were polished with waterproof-polishing papers. The specimens were randomly divided into five groups of 40 teeth each as follows: group 1(control) -- specimens were not treated with any cavity disinfectants. Groups 2--5 (experimental groups) -- dentin surfaces were treated with the following cavity disinfectants, respectively; 2% chlorhexidine solution, 0.1% benzalkonium chloride-based disinfectant, 1% chlorhexidine gel, and an iodine potassium iodide/copper sulfate-based disinfectant. The specimens were then randomly divided into two subgroups including 20 teeth each to evaluate the effect of different bonding systems. Dentin bonding systems were applied to the dentin surfaces and the composite buildups were done. After the specimens were stored in an incubator for 24 hours, the shear bond strength was measured at a crosshead speed of 1 mm/min. The specimens were then statistically analyzed. STATISTICAL ANALYSIS USED: One way analysis of variance and Tukey-HSD tests were used. RESULTS: There was no significant difference between chlorhexidine gel and control groups regardless of the type of the bonding agent used (P>0.05). On the other hand, pretreatment with benzalkonium chloride-based, iodine potassium iodide/copper sulfate-based disinfectants or chlorhexidine solutions had a negative effect on the shear bond strength of self-etching bonding systems. CONCLUSIONS: The findings of this study suggest that when benzalkonium chloride based, iodine potassium iodide/copper sulfate-based disinfectants or chlorhexidine solutions are used as a cavity disinfectant, an etch-and-rinse bonding system should be preferred. PMID- 22090757 TI - In vitro evaluation of influence of salivary contamination on the dentin bond strength of one-bottle adhesive systems. AB - AIM: To evaluate the effect of salivary contamination on the bond strength of one bottle adhesive systems - (the V generation) at various stages during the bonding procedure and to investigate the effect of the contaminant removing treatments on the recovery of bond strengths. MATERIALS AND METHODS: In this study the V generation one-bottle system - (Adper Single Bond) was tested. Fifty caries-free human molars with flat dentin surfaces were randomly divided into five groups of ten teeth each: Group I had 15 second etching with 35% Ortho Phosphoric acid, 15 second rinse and blot dried (Uncontaminated); Group II contaminated and blot dried; Group III contaminated and completely dried; Group IV contaminated, washed, blot dried; Group V contaminated, retched washed, and blot dried. The bonding agent was applied and resin composite (Z-100 3M ESPE) was bonded to the treated surfaces using the Teflon mold. The specimens in each group were then subjected to shear bond strength testing in an Instron Universal testing machine at a crosshead speed of 1 mm / minute and the data were subjected to one way ANOVA for comparison among the groups (P<0.05). RESULTS: There was a significant difference between the group that was dried with strong oil-free air after contamination (Group III) and the other groups. When the etched surface was contaminated by saliva, there was no statistical difference between the just blot dry, wash, or the re-etching groups (Groups II, IV, V) if the dentin surface was kept wet before priming. When the etched dentin surface was dried (Group III) the shear bond strength decreased considerably. CONCLUSION: The bond strengths to the tooth structure of the recent dentin bonding agents are less sensitive to common forms of contamination than assumed. Re-etching without additional mechanical preparation is sufficient to provide or achieve the expected bond strength. PMID- 22090759 TI - Prevalence of tooth size discrepancy among North Indian orthodontic patients. AB - OBJECTIVE: To determine the prevalence of tooth size discrepancy (TSD) in a representative orthodontics population, to explore how many millimeters of TSD is clinically significant and to determine the ability of simple visual inspection to detect such a discrepancy. MATERIALS AND METHODS: The sample comprised 150 pretreatment study casts with fully erupted and complete permanent dentitions from first molar to first molar, which were selected randomly from records of the orthodontic patients. The mesiodistal diameters of the teeth were measured at contact points using digital calipers and the Bolton's analysis was carried out on them. Simple visual estimation of Bolton discrepancy was also performed. RESULTS: In the sample group, 24% of the patients had anterior tooth width ratios and 8% had total arch ratios greater than +/-2 standard deviation (SD) from Bolton's means. For the anterior analysis, correction greater than +/-2 mm was required for 24% of patients in the upper arch or 14% in the lower arch. For the total arch analysis, correction greater than +/-2 mm was required for 36% of patients in the upper arch or 32% in the lower arch. CONCLUSION: Bolton's analysis should be routinely performed in all orthodontic patients and the findings should be included in orthodontic treatment planning. 2 mm of the required tooth size correction is an appropriate threshold for clinical significance. Visual estimation of TSD has low sensitivity and specificity. Careful measurement is more frequently required in clinical practice than visual estimation would suggest. PMID- 22090758 TI - Assessment of antibacterial properties of newer dentin bonding agents: An in vitro study. AB - AIM: To evaluate and compare the antibacterial activity of newer dentin bonding agents on Streptococcus mutans using the direct contact test. MATERIALS AND METHODS: Streptococcus mutans was used as test organism and a direct contact test was performed. The dentin bonding agents to be tested were grouped as Group I, Clearfil Protect Bond, Group II, Adper Easy One, and Group III, Prime and Bond NT. For the direct contact test, three microtiter plates consisting of 96 wells each were taken (288 wells). These wells were divided into three groups of 96 wells; 16 wells of a microtiter plate were utilized, of which four were designated as 'A' wells (with the dentin bonding agent and bacterial suspension), another four as 'B' wells (without the dentin bonding agent, but with the bacterial suspension), another four as the 'C' wells (with the tested material, but without bacteria, which served as the negative control), and the remaining four as the 'D' wells (without the dentin bonding agent, which served as the positive control). Each group was treated with their respective bonding agents as per the manufactures instructions. Broth of 15 MUL was then transferred from the A wells into an adjacent set of B wells containing fresh medium (215 MUL). This resulted in two sets of four wells for each tested material containing an equal volume of liquid medium, so that bacterial growth was monitored both in the presence and in the absence of the tested material. The plate was placed for incubation at 37 degrees C in the microplate reader and the optical density in each well was measured at 600 nm. The readings were taken at regular intervals. (Every 30 minutes for 16 hours). RESULTS: The Dentin bonding agents evaluated in this study showed different inhibitory effects. Clearfil Protect Bond and Prime and Bond NT were most effective, and Adper Easy One was least effective against Streptococcus mutans. INTERPRETATION AND CONCLUSION: The Dentin bonding agents evaluated in this study showed different inhibitory effects. Clearfil Protect Bond and Prime and Bond NT were most effective, and Adper Easy One was the least effective against Streptococcus mutans. Hence, the incorporation of antibacterial agents into the dentin bonding agents may become an essential factor in inhibiting residual bacteria in the cavity and secondary caries. PMID- 22090760 TI - Assessment of crown angulations, crown inclinations, and tooth size discrepancies in a South Indian population. AB - AIMS AND OBJECTIVE: The aim of this study was to assess crown angulations, crown inclinations, and tooth size discrepancy in a sample population from Davangere, South India. MATERIALS AND METHODS: One hundred adults (50 male and 50 female) of age 18-30 years, with Angle's class I ideal occlusion and balanced profiles, were selected for the study. Study models were prepared and crown angulations and crown inclinations were measured using a customized protractor device. Bolton's analysis was used to measure the tooth size discrepancies. RESULTS: Maxillary and mandibular teeth had less crown angulations. Maxillary and mandibular incisors and maxillary molars showed increased crown inclinations, whereas mandibular molars and premolars had less crown inclinations than the original Andrews sample. The mean maxillary and mandibular tooth size ratios, overall and anterior, were similar to Bolton's ratios. CONCLUSIONS: The finding of this study indicates that there are possible racial and ethnic factors contributing to variations in crown angulations and crown inclinations. PMID- 22090761 TI - Comparative evaluation of linear dimensional changes of four commercially available heat cure acrylic resins. AB - CONTEXT: Heat cured acrylic resins undergo dimensional changes during polymerization. Dimensional changes which occur in the heat cure acrylic resins are shrinkage and expansion which affects the fit of the denture and occlusal relationship. AIMS: The purpose of this study was to access the linear dimensional changes of four heat cure acrylic resins before and after curing and compare the changes among four different acrylic brands. MATERIALS AND METHODS: Twenty four patients irrespective of age and sex were taken and four commercially available brands were procured. After the teeth arrangement on the mandibular trial denture, two pins were fixed in central fossae of first molar on both sides and one pin in the cingulum of left central incisor. Meliodent heat cure acrylic resin was used in Group A; Trevalon heat cure acrylic resin was used in Group B; Triplex heat cure acrylic resin was used in Group C and Vertex heat cure acrylic resin was used in Group D. Linear measurements of the trial wax up before and after curing and before and after finishing and polishing were measured and compared. Collected data was analyzed with analysis of variance and 't' test at 95% level of confidence (P=0.05). RESULTS: The maximum percentage changes were seen in cases of Group A (Meliodent) followed by Group B, Group C and Group D (Trevalon, Triplex and Vertex). Meliodent showed the highest percentage change i.e. 1.18% and Vertex showed least percentage change of 0.37 %. CONCLUSIONS: Shrinkage occurred after curing and after finishing and polishing, which varies significantly with the four commercially available heat cure acrylic resins. Among the four different brands of heat cure acrylic resin Group D (Vertex) had the least linear dimensional changes after curing and after finishing and polishing, so that D (Vertex) could be the material of choice for fabrication of complete denture among the four brands. PMID- 22090762 TI - Identification of Candida albicans by using different culture medias and its association in potentially malignant and malignant lesions. AB - BACKGROUND AND OBJECTIVE: The present study evaluates the association of Candida albicans with normal control group, potentially malignant and malignant lesions of oral cavity by using two different liquid culture media. MATERIALS AND METHODS: Saliva was collected and biopsy was taken only from those clinically suspected potentially malignant and malignant lesions for histopathological diagnosis. Saliva samples were inoculated for fungal growth in Sabouraud's dextrose agar and culture-positive samples had undergone for Germ tube test. Germ tube-positive samples were further taken for quantification of chlamydospore production in liquid media at 8 and 16 hours. RESULTS: In normal control groups no fungus growth was found; however, potentially malignant and malignant cases showed fungus growth, positive germ tube test and chlamydospore formation. The result also showed rapid and quantitatively more chlamydospore formation in corn meal broth + 5% milk in comparison to serum milk culture media. CONCLUSION: The oral mucosa is compromised in potentially malignant lesions, it can be argued that this species may be involved in carcinogenesis by elaborating the nitrosamine compounds which either act directly on oral mucosa or interact with other chemical carcinogens to activate specific proto-oncogenes and thereby initiate oral neoplasia. PMID- 22090763 TI - Redesign of a fixture mount to be used as an impression coping and a provisional abutment as well. AB - PURPOSE: An integrated fixture mount/impression coping/ temporary abutment can provide many advantages for immediate loading of dental implants, such as simpler procedure, less chair time, cost reduction, and comfort for the patients. MATERIALS AND METHODS: A newly designed dental implant fixture mount (DIFMA) can be used as an impression coping for taking an immediate impression. An immediate load provisional prosthesis can then be fabricated shortly after implant placement to immediately load the implants. This fixture mount can also serve as a temporary abutment for immediate chair-side fabrication of provisional prosthesis. Two clinical cases are presented. RESULTS: A clinical case utilizing the fixture mount abutment (DIFMA)/implant assembly is presented. The precision of fitting between the impression copings and implants is secured with this system. The chair time for taking an immediate impression is greatly reduced. Less cost for the restoration is provided and patient comfort is delivered. CONCLUSIONS: More patient satisfaction can be conferred by employing the fixture mount in the process of immediate impression taking and as an immediate provisional abutment. PMID- 22090764 TI - Evaluation of mandibular morphology in different facial types. AB - The purpose of this study was to evaluate mandibular morphology in different facial types using various parameters. This study was conducted on lateral cephalograms of a total of 110 subjects, which included 55 males and 55 females between the age of 18-25 years having a mean of 22.3 years for males and 21.5 years for females. The sample was divided into normodivergent, hypodivergent, and hyperdivergent subgroups based on Jarabak's ratio. Symphysis height, depth, ratio (height/depth) and angle, antegonial notch depth, ramal height and width, mandibular depth, upper, lower, and total gonial angle, and mandibular arc angle were analyzed statistically and graphically. It was found that the mandible with the vertical growth pattern was associated with a symphysis with large height, small depth, large ratio, small angle, decreased ramus height and width, smaller mandibular depth, increased gonial angle, and decreased mandibular arc angle in contrast to mandible with a horizontal growth pattern. Sexual dichotomy was found with mean symphysis height and depth in the female sample being smaller than in the male sample, but symphysis ratio was larger in the female sample; males having greater ramus height and width, mandibular depth than females. The mandible seemed to have retained its infantile characteristics with all its processes underdeveloped in hyperdivergent group. PMID- 22090765 TI - Prosthetic rehabilitation of a preschooler with induced anodontia - A clinical report. AB - A case of prosthetic rehabilitation with complete dentures for a three year nine months old child is presented. Dental prosthesis are frequently used to avoid psychologic, speech, or swallowing problems in preschooler children. The case was followed up for a period of three years. These prosthesis were modified as the child grew and as the permanent teeth erupted into the oral cavity the dentures were trimmed from the areas of erupting teeth to facilitate their eruption. PMID- 22090766 TI - Dentigerous cyst associated with multiple complex composite odontomas. AB - Odontomas are considered to be hamartomatous malformations rather than true neoplasms. This most common odontogenic lesion results from the growth of completely differentiated epithelial and mesenchymal cells that give rise to ameloblasts and odontoblasts. Dentigerous cyst is an epithelium-lined sac enclosing the crown of an unerupted tooth. Apparently, the dentigerous cyst arises by the accumulation of fluid between reduced enamel epithelium and the tooth crown. Occasionally it is associated with supernumerary tooth or odontoma. We report a case of dentigerous cyst associated with complex composite odontoma and an impacted lateral incisor in a 30-year-old male patient. PMID- 22090767 TI - Compound odontoma associated with an unerupted rotated and dilacerated maxillary central incisor. AB - Odontomas are benign tumors containing various component tissues of teeth. They usually remain asymptomatic and are diagnosed on routine radiographs. Clinically, they are often associated with delayed eruption or impaction of permanent teeth and retained primary teeth. A case of compound odontoma in association with an unerupted, rotated and dilacerated maxillary permanent right central incisor in a 12-year-old boy is reported. Such combination is rare, making it an interesting case for reporting. We have also discussed the clinical features, diagnosis and treatment of such a condition. PMID- 22090768 TI - Pierre robin sequence and the pediatric dentist. AB - This article on the dental management of a neonate with Pierre Robin sequence describes the clinical and laboratory procedures for construction of a feeding plate due to the presence of a cleft palate. Emphasis has also been laid on a few literatures to describe medical complications associated with this condition. A 56-day-old neonate had been referred to the outpatient department with the complaint of difficulty in feeding, description, and management of which has been described in the case report. PMID- 22090769 TI - Immediate fixed temporization with a natural tooth crown pontic following failure of replantation. AB - Extracted teeth can be bonded directly to adjacent teeth utilizing a prefabricated composite resin framework reinforced with polyethylene fiber as a noninvasive long-term provisional tooth replacement. This immediate provisional restoration allow for exact repositioning of the coronal part of the extracted tooth in its original intraoral three-dimensional position and thus relieves the apprehension of the patient caused by the sudden loss of an anterior tooth. PMID- 22090770 TI - Mandibular adenomatoid odontogenic tumor: A report of an unusual case. AB - Adenomatoid odontogenic tumor (AOT) is a slow-growing, benign tumor that appears in the anterior portion of the jaws and more frequently, the anterior maxilla usually in association with the crowns of unerupted teeth. Most of the tumors are diagnosed in second decade of life. A rare case report of AOT associated with an impacted right mandibular first premolar in a 24-year-old female is reported. PMID- 22090771 TI - A case of desmoplastic ameloblastoma occupying maxillary sinus. AB - We report a rare case of desmoplastic ameloblastoma lesion that filled the entire maxillary sinus. The patient visited our hospital with a chief complaint of swelling around the upper left premolars. A panoramic X-ray captured an image of a mixture of ill-defined radiolucency and radiopacity from the swollen area to the maxillary sinus. Computed tomography (CT) and Magnetic resononce imaging (MRI) showed that the lesion occupied almost the entire left maxillary sinus and had entered the nasal cavity. A pathologic diagnosis of ameloblastoma was made after biopsy, and the tumor was removed and the marginal bone curetted under general anesthesia. A CT scan at 4 months postoperatively indicated the presence of residual and recurrent tumor in the area of the upper left lateral incisor, and removal and curettage were performed again. Recurrence may be detected relatively easily based on radiographic characteristics, and therefore follow-up with an X-ray examination such as a CT scan is important. PMID- 22090772 TI - Buccal-sided mandibular angle exostosis - A rare case report. AB - Buccal exostoses are benign, broad-based surface masses of the outer or facial aspect of the maxilla and less commonly, the mandible. They begin to develop in early adulthood and may very slowly enlarge over the years. They are painless and self-limiting, but occasionally may become several centimeters across and then contribute to periodontal disease of the adjacent teeth by forcing food during chewing in toward the teeth instead of away from them, as is normally the case. The following paper presents a very rare case of buccal-sided mandibular angle exoxtosis and its management with surgical exploration. PMID- 22090773 TI - Pyogenic granuloma associated with periodontal abscess and bone loss - A rare case report. AB - A diverse group of the pathologic process can produce the enlargement of soft tissues in the oral cavity and often present a diagnostic challenge. This soft tissue enlargement may represent a variation of the normal anatomic structure, inflammatory reaction, cyst, neoplasm, and developmental anomalies. A group of reactive hyperplasias, which develop in response to chronic recurring tissue injury that stimulates an excessive tissue repair response. The pyogenic granuloma (PG) is a reactive enlargement that is an inflammatory response to local irritation such as calculus, a fractured tooth, rough dental restoration, and foreign materials or hormonal (pregnancy tumor) and rarely associated with bone loss. This paper presents a rare case of PG associated with periodontal abscess and bone loss in a 30-year-old male. PMID- 22090774 TI - Franceschetti syndrome. AB - Franceschetti syndrome is an autosomal dominant disorder of craniofacial development with variable expressivity. It is commonly known as Treacher Collins syndrome (TCS). It is named after E. Treacher Collins who described the essential components of the condition. It affects both genders equally. This article reports a case of TCS in an 18-year-old female. PMID- 22090775 TI - Central giant cell granuloma mimicking an adenomatoid odontogenic tumor. AB - Central giant cell granulomas are non-neoplastic lesions of unknown etiology. They affect females more than males with the mandibular anterior region being the most common site of occurrence. Clinically central giant cell granulomas present as asymptomatic, expansile swellings causing deviation of associated teeth. Radiologically they usually presents as multilocular lesions causing expansion or perforation of cortical bone. Central giant cell granulomas are usually confused as other lesions both clinically and radiologically, and a definitive diagnosis can be made only histologically. We report here a rare case of central giant cell granuloma in association with congenitally missing tooth which was misdiagnosed to be an adenomatoid odontogenic tumor both clinically and radiologically. This case report also highlights yet another unique presentation of central giant cell granulomas that is in association with a congenitally missing maxillary lateral incisor. PMID- 22090776 TI - Split obturator: An innovative approach. AB - A palatal prosthesis can improve function by closing the palatal defect, preventing regurgitation, and improving swallowing and speech. Although techniques have been previously described for fabrication of palatal obturator, but there has not been any technique to devise an obturator for a patient with palatal defect with a quadhelix orthodontic appliance overlying it. One cannot wait in such patients for completion of lengthy orthodontic treatment and then think of devising prosthesis as the patient cannot carry out normal functions like swallowing and speech without the closure of defect. This article focuses on an innovative method of fabricating a palatal obturator which aims at restoring the above-mentioned functions along with improving aesthetics. It also enables us to devise the fabrication of prosthesis in two parts for easy insertion and removal and as well as to be self-cleansable. Such prosthesis would markedly improve patient psychology and confidence. PMID- 22090777 TI - Step-by-step full mouth rehabilitation of a nasopharyngeal carcinoma patient with tooth and implant-supported prostheses: A clinical report. AB - This clinical report presents a 46-year-old man diagnosed with nasopharyngeal carcinoma with the chief complaint of masticatory and speech deficiency because of radiation therapy. After a period of controlling post radiation caries, the patient was rehabilitated with tooth and implant supported metal ceramic restorations following surgical and endodontic intervention. PMID- 22090778 TI - Congenital hemifacial hyperplasia. AB - Congenital hemifacial hyperplasia (CHH) is a rare congenital malformation characterized by marked unilateral overdevelopment of hard and soft tissues of the face. Asymmetry in CHH is usually evident at birth and accentuated with age, especially at puberty. The affected side grows at a rate proportional to the nonaffected side so that the disproportion is maintained thr oughout the life. Multisystem involvement has resulted in etiological heterogeneity including heredity, chromosomal abnormalities, atypical forms of twinning, altered intrauterine environment, and endocrine dysfunctions; however, no single theory explains the etiology adequately. Deformities of all tissues of face, including teeth and their related tissues in the jaw, are key findings for correct diagnosis of CHH. Here an attempt has been made to present a case of CHH with its archetypal features and to supplement existing clinical knowledge. PMID- 22090779 TI - True vertical tooth root fracture: Case report and review. AB - It is important for the clinician not only to gather as much information about a case as possible, but also to be able to correctly interpret the data to arrive at an accurate diagnosis. Occasionally, a case presents with symptoms that might be suggestive of a condition; however, the final diagnosis may be totally different. This paper reports on an interesting case of a true vertical root fracture, in an intact maxillary molar in a 55-year-old man. The case was misdiagnosed and treated as a periodontal defect for over two months. The paper discusses the various causes and diagnostic dilemmas of root fractures. PMID- 22090780 TI - Systematic review of modulators of benzodiazepine receptors in irritable bowel syndrome: is there hope? AB - Several drugs are used in the treatment of irritable bowel syndrome (IBS) but all have side effects and variable efficacy. Considering the role of the gut-brain axis, immune, neural, and endocrine pathways in the pathogenesis of IBS and possible beneficial effects of benzodiazepines (BZD) in this axis, the present systematic review focuses on the efficacy of BZD receptor modulators in human IBS. For the years 1966 to February 2011, all literature was searched for any articles on the use of BZD receptor modulators and IBS. After thorough evaluation and omission of duplicate data, 10 out of 69 articles were included. BZD receptor modulators can be helpful, especially in the diarrhea-dominant form of IBS, by affecting the inflammatory, neural, and psychologic pathways, however, controversies still exist. Recently, a new BZD receptor modulator, dextofisopam was synthesized and studied in human subjects, but the studies are limited to phase IIb clinical trials. None of the existing trials considered the neuroimmunomodulatory effect of BZDs in IBS, but bearing in mind the concentration-dependent effect of BZDs on cytokines and cell proliferation, future studies using pharmacodynamic and pharmacokinetic approaches are highly recommended. PMID- 22090782 TI - Advanced endoscopic imaging in Barrett's oesophagus: a review on current practice. AB - Over the last few years, improvements in endoscopic imaging technology have enabled identification of dysplasia and early cancer in Barrett's oesophagus. New techniques should exhibit high sensitivities and specificities and have good interobserver agreement. They should also be affordable and easily applicable to the community gastroenterologist. Ideally, these modalities must exhibit the capability of imaging wide areas in real time whilst enabling the endoscopist to specifically target abnormal areas. This review will specifically focus on some of the novel endoscopic imaging modalities currently available in routine practice which includes chromoendoscopy, autofluorescence imaging and narrow band imaging. PMID- 22090781 TI - Factors predicting occurrence and prognosis of hepatitis-B-virus-related hepatocellular carcinoma. AB - Primary liver cancer is an important cause of cancer death, and hepatocellular carcinoma (HCC) accounts for 70%-85% of total liver cancer worldwide. Chronic hepatitis B virus (HBV) infection contributes to > 75% of HCC cases. High serum viral load is the most reliable indicator of viral replication in predicting development of HCC. HBV genotype C is closely associated with HCC in cirrhotic patients aged > 50 years, whereas genotype B is associated with development of HCC in non-cirrhotic young patients and postoperative relapse of HCC. Different HBV subgenotypes have distinct patterns of mutations, which are clearly associated with increased risk of HCC. Mutations accumulate during chronic HBV infection and predict occurrence of HCC. Chronic inflammation leads to increased frequency of viral mutation via cellular cytidine deaminase induction. Mutations are negatively selected by host immunity, whereas some immuno-escaped HBV mutants are active in hepatocarcinogenesis. Inflammatory pathways contribute to the inflammation-necrosis-regeneration process, ultimately HCC. Their hallmark molecules can predict malignancy in HBV-infected subjects. Continuing inflammation is involved in hepatocarcinogenesis and closely related to recurrence and metastasis. HBV load, genotype C, viral mutations and expression of inflammatory molecules in HBV-related HCC tissues are significantly associated with poor prognosis. Imbalance between intratumoral CD8(+) T cells and regulatory T cells or Th1 and Th2 cytokines in peritumoral tissues can predict prognosis of HBV-related HCC. These factors are important for developing active prevention and surveillance of HBV-infected subjects who are more likely to develop HCC, or for tailoring suitable treatment to improve survival or postpone postoperative recurrence of HCC. PMID- 22090783 TI - Functional imaging and endoscopy. AB - The emergence of endoscopy for the diagnosis of gastrointestinal diseases and the treatment of gastrointestinal diseases has brought great changes. The mere observation of anatomy with the imaging mode using modern endoscopy has played a significant role in this regard. However, increasing numbers of endoscopies have exposed additional deficiencies and defects such as anatomically similar diseases. Endoscopy can be used to examine lesions that are difficult to identify and diagnose. Early disease detection requires that substantive changes in biological function should be observed, but in the absence of marked morphological changes, endoscopic detection and diagnosis are difficult. Disease detection requires not only anatomic but also functional imaging to achieve a comprehensive interpretation and understanding. Therefore, we must ask if endoscopic examination can be integrated with both anatomic imaging and functional imaging. In recent years, as molecular biology and medical imaging technology have further developed, more functional imaging methods have emerged. This paper is a review of the literature related to endoscopic optical imaging methods in the hopes of initiating integration of functional imaging and anatomical imaging to yield a new and more effective type of endoscopy. PMID- 22090784 TI - Heme oxygenase-1 system and gastrointestinal inflammation: a short review. AB - Heme oxygenase-1 (HO-1) system catalyzes heme to biologically active products: carbon monoxide, biliverdin/bilirubin and free iron. It is involved in maintaining cellular homeostasis and many physiological and pathophysiological processes. A growing body of evidence indicates that HO-1 activation may play an important protective role in acute and chronic inflammation of gastrointestinal tract. This review focuses on the current understanding of the physiological significance of HO-1 induction and its possible roles in the gastrointestinal inflammation studied to date. The ability to upregulate HO-1 by pharmacological means or using gene therapy may offer therapeutic strategies for gastrointestinal inflammation in the future. PMID- 22090785 TI - rAd-p53 enhances the sensitivity of human gastric cancer cells to chemotherapy. AB - AIM: To investigate potential antitumor effects of rAd-p53 by determining if it enhanced sensitivity of gastric cancer cells to chemotherapy. METHODS: Three gastric cancer cell lines with distinct levels of differentiation were treated with various doses of rAd-p53 alone, oxaliplatin (OXA) alone, or a combination of both. Cell growth was assessed with an 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5 diphenytetrazoliumromide assay and the expression levels of p53, Bax and Bcl-2 were determined by immunohistochemistry. The presence of apoptosis and the expression of caspase-3 were determined using flow cytometry. RESULTS: Treatment with rAd-p53 or OXA alone inhibited gastric cancer cell growth in a time- and dose-dependent manner; moreover, significant synergistic effects were observed when these treatments were combined. Immunohistochemical analysis demonstrated that treatment with rAd-p53 alone, OXA alone or combined treatment led to decreased Bcl-2 expression and increased Bax expression in gastric cancer cells. Furthermore, flow cytometry showed that rAd-p53 alone, OXA alone or combination treatment induced apoptosis of gastric cancer cells, which was accompanied by increased expression of caspase-3. CONCLUSION: rAd-p53 enhances the sensitivity of gastric cancer cells to chemotherapy by promoting apoptosis. Thus, our results suggest that p53 gene therapy combined with chemotherapy represents a novel avenue for gastric cancer treatment. PMID- 22090786 TI - Casticin-induced apoptosis involves death receptor 5 upregulation in hepatocellular carcinoma cells. AB - AIM: To investigate the apoptotic activities of casticin in hepatocellular carcinoma (HCC) cells and its molecular mechanisms. METHODS: PLC/PRF/5 and Hep G2 cell lines were cultured in vitro and the inhibitory effect of casticin on the growth of cells was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolim bromide (MTT) assay. The apoptotic cell death was examined using the cell apoptosis enzyme linked immunosorbent assay (ELISA) detection kit, flow cytometry (FCM) after propidium iodide (PI) staining and DNA agarose gel electrophoresis. The caspase activities were measured using ELISA. Reactive oxygen species (ROS) production was evaluated by FCM after dichlorodihydrofluorescein diacetate (DCFH-DA) probe labeling. Intracellular glutathione (GSH) content was measured using a glutathione assay kit. The expression of death receptor (DR)4 and DR5 proteins was analyzed by Western blotting and FCM. RESULTS: Casticin significantly inhibited the growth of human HCC (PLC/PRF/5 and Hep G2) cells in a dose-dependent manner (P < 0.05). Casticin increased the percentage of the sub-G1 population in HCC cells in a concentration dependent manner. The potency of casticin to PLC/PRF/5 cells was higher than that of 5-flurouracil (26.8% +/- 4.8% vs 17.4% +/- 5.1%) at 10 MUmol/L for 24 h. Casticin increased the levels of Histone/DNA fragmentation and the levels of active caspase-3, -8 and -9 in a concentration-dependent manner (P < 0.05). Treatment with 30 MUmol/L casticin for 24 h resulted in the formation of a DNA ladder. Casticin reduced the GSH content (P < 0.05), but did not affect the level of intracellular ROS in PLC/PRF/5 and Hep G2 cells. The thiol antioxidants, acetylcysteine (NAC) and GSH restored GSH content and attenuated casticin-induced apoptosis. In contrast, the nonthiol antioxidants, butylated hydroxyanisole and mannitol failed to do so. In the HCC cells treated with casticin for 24 h, DR5 protein level was increased. The expression of DR5 protein induced by casticin was inhibited by NAC. Pretreatment with DR5/Fc chimera protein, a blocking antibody, effectively attenuated the induction of apoptosis by casticin. CONCLUSION: Casticin-induced apoptosis of HCC cells is involved in GSH depletion and DR5 upregulation. PMID- 22090787 TI - High resolution colonoscopy in a bowel cancer screening program improves polyp detection. AB - AIM: To compare high resolution colonoscopy (Olympus Lucera) with a megapixel high resolution system (Pentax HiLine) as an in-service evaluation. METHODS: Polyp detection rates and measures of performance were collected for 269 colonoscopy procedures. Five colonoscopists conducted the study over a three month period, as part of the United Kingdom bowel cancer screening program. RESULTS: There were no differences in procedure duration (chi2 P = 0.98), caecal intubation rates (chi2 P = 0.67), or depth of sedation (chi2 P = 0.64). Mild discomfort was more common in the Pentax group (chi2 P = 0.036). Adenoma detection rate was significantly higher in the Pentax group (chi2 test for trend P = 0.01). Most of the extra polyps detected were flat or sessile adenomas. CONCLUSION: Megapixel definition colonoscopes improve adenoma detection without compromising other measures of endoscope performance. Increased polyp detection rates may improve future outcomes in bowel cancer screening programs. PMID- 22090788 TI - Role of surgical intervention in managing gastrointestinal metastases from lung cancer. AB - AIM: To investigate the clinicopathological characteristics of late-stage lung cancer patients with gastrointestinal (GI)-tract metastases, focusing on therapeutic options and outcomes. METHODS: Our institution (the National Taiwan University Hospital) diagnosed 8159 patients with lung cancer between 1987 and 2008, of which 21 developed symptomatic GI metastases. This study reviewed all of the patients' information, including survival data, pathological reports, and surgical notes. RESULTS: The most common histological type of lung cancer was adenocarcinoma, and 0.26% of patients with lung cancer developed GI metastases. The median duration from lung cancer diagnosis to GI metastases was three months (range, 0-108 mo), and the average time from diagnosis of GI metastasis to death was 2.8 mo. Most patients with symptomatic gastric and/or duodenal metastases exhibited GI bleeding and were diagnosed by panendoscopy. In contrast, small bowel metastases typically presented as an acute abdomen and were not diagnosed until laparotomy. All patients with small bowel or colonic metastases underwent surgical intervention, and their perioperative mortality was 22%. Our data revealed a therapeutic effect in patients with solitary GI metastasis and a favorable palliative effect on survival when metastases were diagnosed preoperatively. In patients with multiple GI metastases, the presentation varied according to the locations of the metastases. CONCLUSION: Surgical treatment is worthwhile in a select group of patients with bowel perforation or obstruction. Physicians should be more alert to symptoms or signs indicating GI metastases. PMID- 22090790 TI - Sixty-four-slice computed tomography in surgical strategy of portal vein cavernous transformation. AB - AIM: To investigate the role of 64-slice computed tomography (CT) in portal vein cavernous transformation to determine surgical strategy. METHODS: The site of lesions and extent of collateral circulation in 12 pediatric cases of cavernous transformation of the portal vein with surgical treatment were analyzed. RESULTS: Eleven of 12 children had esophageal varices and were treated with lower esophageal and gastric devascularization and splenectomy, and the other case was only treated with splenectomy. There were eight cases with spontaneous spleen/stomach-renal shunt, four with Retzius vein opening, which was reserved during surgery. Three cases of lesions involving the intrahepatic portal vein (PV) were treated with living donor liver transplantation. One patient died from PV thrombosis after liver transplantation, and the rest had no significant complications. CONCLUSION: The PV, its branches and collateral circulation were clearly seen by 64-slice spiral CT angiography, which helped with preoperative surgical planning. PMID- 22090789 TI - A meta-analysis of lamivudine for interruption of mother-to-child transmission of hepatitis B virus. AB - AIM: To determine the therapeutic effect of lamivudine in late pregnancy for the interruption of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: Studies were identified by searching available databases up to January 2011. Inclusive criteria were HBV-carrier mothers who had been involved in randomized controlled clinical trials (RCTs) with lamivudine treatment in late pregnancy, and newborns or infants whose serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) or HBV DNA had been documented. The relative risks (RRs) for interruption of MTCT as indicated by HBsAg, HBV DNA or HBeAg of newborns or infants were calculated with 95% confidence interval (CI) to estimate the efficacy of lamivudine treatment. RESULTS: Fifteen RCTs including 1693 HBV-carrier mothers were included in this meta-analysis. The overall RR was 0.43 (95% CI, 0.25-0.76; 8 RCTs; P(heterogeneity) = 0.04) and 0.33 (95% CI, 0.23 0.47; 6 RCTs; P(heterogeneity) = 0.93) indicated by newborn HBsAg or HBV DNA. The RR was 0.33 (95% CI, 0.21-0.50; 6 RCTs; P(heterogeneity) = 0.46) and 0.32 (95% CI, 0.20-0.50; 4 RCTs; P(heterogeneity) = 0.33) indicated by serum HBsAg or HBV DNA of infants 6-12 mo after birth. The RR (lamivudine vs hepatitis B immunoglobulin) was 0.27 (95% CI, 0.16-0.46; 5 RCTs; P(heterogeneity) = 0.94) and 0.24 (95% CI, 0.07-0.79; 3 RCTs; P(heterogeneity) = 0.60) indicated by newborn HBsAg or HBV DNA, respectively. In the mothers with viral load < 106 copies/mL after lamivudine treatment, the efficacy (RR, 95% CI) was 0.33, 0.21-0.53 (5 RCTs; P(heterogeneity) = 0.82) for the interruption of MTCT, however, this value was not significant if maternal viral load was > 106 copies/mL after lamivudine treatment (P = 0.45, 2 RCTs), as indicated by newborn serum HBsAg. The RR (lamivudine initiated from 28 wk of gestation vs control) was 0.34 (95% CI, 0.22 0.52; 7 RCTs; P(heterogeneity) = 0.92) and 0.33 (95% CI, 0.22-0.50; 5 RCTs; P(heterogeneity) = 0.86) indicated by newborn HBsAg or HBV DNA. The incidence of adverse effects of lamivudine was not higher in the mothers than in controls (P = 0.97). Only one study reported side effects of lamivudine in newborns. CONCLUSION: Lamivudine treatment in HBV carrier-mothers from 28 wk of gestation may interrupt MTCT of HBV efficiently. Lamivudine is safe and more efficient than hepatitis B immunoglobulin in interrupting MTCT. HBV MTCT might be interrupted efficiently if maternal viral load is reduced to < 106 copies/mL by lamivudine treatment. PMID- 22090791 TI - Comparison of laparoscopic and open surgery for pyogenic liver abscess with biliary pathology. AB - AIM: To investigate the feasibility and therapeutic effect of laparoscopic surgery for pyogenic liver abscess (PLA) with biliary pathology. METHODS: From January 2004 to October 2010, 31 patients with PLA combined with biliary pathology meeting entry criteria received surgical management in our hospital. Of the 31 patients, 13 underwent laparoscopic surgery (LS group) and 18 underwent open surgery (OS group). Clinical data including operation time, intraoperative blood loss, postoperative complication rate, length of postoperative hospital stay, and abscess recurrence rate were retrospectively analyzed and compared between the two groups. RESULTS: All patients received systemic antibiotic therapy. Four patients underwent ultrasound-guided percutaneous catheter drainage before operation. Postoperative complications occurred in 5 patients (16.1%, 5/31) including 2 in the LS group and 3 in the OS group. One patient had retained calculus in the common bile duct and another had liver abscess recurrence in the OS group. No retained calculus and liver abscess recurrence occurred in the LS group. In the two groups, there was no mortality during the perioperative period. There were no significant differences in operation time, intraoperative blood loss and transfusion, postoperative complication rate and abscess recurrence rate between the two groups. Oral intake was earlier (1.9 +/- 0.4 d vs 3.1 +/- 0.7 d, P < 0.05) and length of postoperative hospital stay was shorter (11.3 +/- 2.9 d vs 14.5 +/- 3.7 d, P < 0.05) in the LS group than in the OS group. CONCLUSION: Laparoscopic surgery for simultaneous treatment of PLA and biliary pathology is feasible in selected patients and the therapeutic effect is similar to that of open surgery. PMID- 22090792 TI - Sudden blindness in a child with Crohn's disease. AB - Inflammatory bowel disease (IBD) is often associated with extraintestinal manifestations (EIMs) such as optic neuritis (ON), although this has been described in only a few adult patients so far, all of whom were affected with Crohn's disease (CD). Furthermore, ON and demyelinating diseases have been demonstrated to be more frequent in IBD patients than in control populations. In our current case report, we describe a child with active CD who developed sudden blindness due to bilateral ON that was not related to any known cause, and that promptly responded to a high dose of steroids. Investigations and a clinical follow-up have so far ruled out the development of demyelinating diseases in this patient. To our knowledge, this is the first report of ON in a pediatric patient with CD. Possible explanations for this case include an episodic EIM of an active bowel disease, an associated autoimmune disorder such as a recurrent isolated ON, the first manifestation of multiple sclerosis, or another demyelinating disease that could appear in a later follow-up. PMID- 22090793 TI - Regional lymphadenectomy strongly recommended in T1b gallbladder cancer. AB - This article discusses the adequate treatment of early gallbladder cancer (T1a, T1b) and is based on published studies extending over nearly 3 decades. Randomized studies and meta analyses comparing different surgical treatments do not exist. The literature shows that in up to 20% of patients lymph node metastasis are found in T1b gallbladder cancer. Due to high malignancy with early angiolymphatic spread and resistance to chemotherapy and radiation on the one hand, and the relative low operative risk of extended cholecystectomy (cholecystectomy and regional lymphadenectomy) on the other hand, we believe that this procedure is mandatory in early gallbladder cancer. PMID- 22090794 TI - Characterization and Analysis of Relative Intensity Noise in Broadband Optical Sources for Optical Coherence Tomography. AB - Relative intensity noise (RIN) is one of the most significant factors limiting the sensitivity of an optical coherence tomography (OCT) system. The existing and prevalent theory being used for estimating RIN for various light sources in OCT is questionable, and cannot be applied uniformly for different types of sources. The origin of noise in various sources differs significantly, owing to the different physical nature of photon generation. In this study, we characterize and compare RIN of several OCT light sources including superluminescent diodes (SLDs), an erbium-doped fiber amplifier, multiplexed SLDs, and a continuous-wave laser. We also report a method for reduction of RIN by amplifying the SLD light output by using a gain-saturated semiconductor optical amplifier. PMID- 22090795 TI - Developing Survey Research Infrastructure At An Historically Black College/University To Address Health Disparities. AB - This article describes the development of the Center for Survey Research at Shaw University, a Historically Black College and University (HBCU), and its efforts to build a data collection infrastructure that addresses issues germane to health disparities research in the African American population. Academic institutions that are similar to Shaw in size, mission, and background can use the Project EXPORT collaboration and the Center for Survey Research as models for establishing their own research infrastructure and subsequent survey center in order to address health disparities through the use of survey methodology. PMID- 22090796 TI - Concordance, compliance, preference or adherence. PMID- 22090797 TI - Clinical utility of the risperidone formulations in the management of schizophrenia. AB - Risperidone is one of the early second-generation antipsychotics that came into the limelight in the early 1990s. Both the oral and long-acting injectable formulations have been subject to numerous studies to assess their safety, efficacy, and tolerability. Risperidone is currently one of the most widely prescribed antipsychotic medications, used for both acute and long-term maintenance in schizophrenia. Risperidone has better efficacy in the treatment of psychotic symptoms than placebo and possibly many first-generation antipsychotics. Risperidone fares better than placebo and first-generation antipsychotics in the treatment of negative symptoms. Risperidone's long acting injectable preparation has been well tolerated and is often useful in patients with medication nonadherence. Risperidone has a higher risk of hyperprolactinemia comparable to first-generation antipsychotics (FGAs) but fares better than many second-generation antipsychotics with regards to metabolic side effects. In this article, we briefly review the recent literature exploring the role of risperidone formulations in schizophrenia, discuss clinical usage, and highlight the controversies and challenges associated with its use. PMID- 22090798 TI - Antianxiety medications for the treatment of complex agoraphobia: pharmacological interventions for a behavioral condition. AB - BACKGROUND: Although there are controversial issues (the "American view" and the "European view") regarding the construct and definition of agoraphobia (AG), this syndrome is well recognized and it is a burden in the lives of millions of people worldwide. To better clarify the role of drug therapy in AG, the authors summarized and discussed recent evidence on pharmacological treatments, based on clinical trials available from 2000, with the aim of highlighting pharmacotherapies that may improve this complex syndrome. METHODS: A systematic review of the literature regarding the pharmacological treatment of AG was carried out using MEDLINE, EBSCO, and Cochrane databases, with keywords individuated by MeSH research. Only randomized, placebo-controlled studies or comparative clinical trials were included. RESULTS: After selection, 25 studies were included. All the selected studies included patients with AG associated with panic disorder. Effective compounds included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, selective noradrenergic reuptake inhibitors, and benzodiazepines. Paroxetine, sertraline, citalopram, escitalopram, and clomipramine showed the most consistent results, while fluvoxamine, fluoxetine, and imipramine showed limited efficacy. Preliminary results suggested the potential efficacy of inositol; D-cycloserine showed mixed results for its ability to improve the outcome of exposure-based cognitive behavioral therapy. More studies with the latter compounds are needed before drawing definitive conclusions. CONCLUSION: No studies have been specifically oriented toward evaluating the effect of drugs on AG; in the available studies, the improvement of AG might have been the consequence of the reduction of panic attacks. Before developing a "true" psychopharmacology of AG it is crucial to clarify its definition. There may be several potential mechanisms involved, including fear learning processes, balance system dysfunction, high light sensitivity, and impaired visuospatial abilities, but further studies are warranted. PMID- 22090799 TI - Polypharmacy or medication washout: an old tool revisited. AB - There has been a rapid increase in the use of polypharmacy in psychiatry possibly due to the introduction of newer drugs, greater availability of these newer drugs, excessive confidence in clinical trial results, widespread prescribing of psychotropic medications by primary care, and pressure to augment with additional medications for unresolved side effects or greater efficacy. Even the new generation of medications may not hold significant advantages over older drugs. In fact, there may be additional safety risks with polypharmacy being so widespread. Washout, as a clinical tool, is rarely done in medication management today. Studies have shown that augmenting therapy with additional medications resulted in 9.1%-34.1% dropouts due to intolerance of the augmentation, whereas studies of medication washout demonstrated only 5.9%-7.8% intolerance to the washout procedure. These perils justify reconsideration of medication washout before deciding on augmentation. There are unwarranted fears and resistance in the medical community toward medication washout, especially at the moment a physician is trying to decide whether to washout or add more medications to the treatment regimen. However, medication washout provides unique benefits to the physician: it establishes a new baseline of the disorder, helps identify medication efficacy from their adverse effects, and provides clarity of diagnosis and potential reduction of drug treatments, drug interactions, and costs. It may also reduce overall adverse events, not to mention a potential to reduce liability. After washout, physicians may be able to select the appropriate polypharmacy more effectively and safely, if necessary. Washout, while not for every patient, may be an effective tool for physicians who need to decide on whether to add potentially risky polypharmacy for a given patient. The risks of washout may, in some cases, be lower and the benefits may be clearly helpful for diagnosis, understanding medication effects, the doctor/patient relationship, and safer use of polypharmacy if indicated. PMID- 22090800 TI - Brain activity modification produced by a single radioelectric asymmetric brain stimulation pulse: a new tool for neuropsychiatric treatments. Preliminary fMRI study. AB - PURPOSE: Radioelectric asymmetric brain stimulation technology with its treatment protocols has shown efficacy in various psychiatric disorders. The aim of this work was to highlight the mechanisms by which these positive effects are achieved. The current study was conducted to determine whether a single 500 millisecond radioelectric asymmetric conveyor (REAC) brain stimulation pulse (BSP), applied to the ear, can effect a modification of brain activity that is detectable using functional magnetic resonance imaging (fMRI). METHODS: Ten healthy volunteers, six females and four males, underwent fMRI during a simple finger-tapping motor task before and after receiving a single 500-millisecond REAC-BSP. RESULTS: The fMRI results indicate that the average variation in task induced encephalic activation patterns is lower in subjects following the single REAC pulse. CONCLUSION: The current report demonstrates that a single REAC-BSP is sufficient to modulate brain activity in awake subjects, able to be measured using fMRI. These initial results open new perspectives into the understanding of the effects of weak and brief radio pulses upon brain activity, and provide the basis for further indepth studies using REAC-BSP and fMRI. PMID- 22090801 TI - Predisposition for borderline personality disorder with comorbid major depression is associated with that for polycystic ovary syndrome in female Japanese population. AB - Polycystic ovary syndrome (PCOS) is a common lifestyle-related endocrinopathy in women of reproductive age and is associated with several mental health problems. We examined the genotypic distributions of IRS-1 Gly972Arg and CYP11B2 -344T/C, which were previously described as influencing PCOS, and assayed the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), in a set of female patients with borderline personality disorder (BPD) with comorbid major depressive disorder (MDD) (n = 50) and age-matched control subjects (n = 100), to investigate the predisposition for BPD with MDD. The results showed that the patients were more frequently IRS-1 972Arg variant allele carriers (P = 0.013; OR 6.68; 95% CI = 1.30-34.43) and homozygous for the CYP11B2 -344C variant allele (P = 0.022; OR = 3.32; 95% CI = 1.18-9.35) than the control subjects. The IL-6 level was significantly higher in the patients than in the controls (P < 0.0001). There was no significant difference in the serum TNF-alpha level between patients with BPD with MDD and the healthy comparison group (P = 0.5273). In conclusion, the predisposition for BPD with MDD is associated with that for PCOS, in the female Japanese population. An elevated serum IL-6 level is considered to be a possible biomarker of BPD with MDD. PMID- 22090802 TI - Incidence and impact of pain conditions and comorbid illnesses. AB - BACKGROUND: Individuals with pain often present with more than one painful condition. The purpose of this study was to characterize the rates of comorbidity, pain medication use, and health care costs for 23 selected pain conditions in a large health plan using administrative claims data from 2005 to 2007. METHODS: Eligible patients included 1,211,483 adults with at least one pain condition during the one-year study period. Pain condition cohorts were classified based on the first diagnosis present in the claims during the study period. RESULTS: Musculoskeletal pain conditions were among the most prevalent cohorts including low back pain, osteoarthritis, and fibromyalgia. Cancer pain was the least prevalent cohort. Conditions with the lowest illness severity included migraine and painful bladder syndrome cohorts, while cohorts with diabetic neuropathy, human immunodeficiency virus (HIV)-associated pain, and cancer pain were the most severe. Across cohorts, the mean number of comorbid pain conditions ranged from 1.39 (for cancer pain and migraine) to 2.65 (for multiple sclerosis pain). High rates of mental health conditions were found in cohorts with HIV-associated pain and multiple sclerosis pain (42.59% and 34.78%) and were lowest among cohorts with rheumatoid arthritis and psoriatic arthropathy (12.73% and 13.31%), respectively. Rates of sleep disorders ranged from 5.47% (for painful bladder syndrome) to 11.59% (for multiple sclerosis pain). Overall, patients averaged 3.53 unique pain medications during the study period. Considerable annual total health care costs were observed in the cancer pain cohort and the lowest costs were observed in the postherpetic neuropathy, surgically-induced pain, migraine, and irritable bowel syndrome cohorts. Costs attributed to pain were highest among the multiple sclerosis, HIV, and cancer pain cohorts. The highest pharmaceutical costs were observed in the HIV cohort. CONCLUSION: These findings underscore the heterogeneity of patients with pain in terms of burden of illness, costs to the health care system, and the complexity of commonly co-occurring disorders. PMID- 22090803 TI - Increased levels of SV2A botulinum neurotoxin receptor in clinical sensory disorders and functional effects of botulinum toxins A and E in cultured human sensory neurons. AB - BACKGROUND: There is increasing evidence that botulinum neurotoxin A may affect sensory nociceptor fibers, but the expression of its receptors in clinical pain states, and its effects in human sensory neurons, are largely unknown. METHODS: We studied synaptic vesicle protein subtype SV2A, a receptor for botulinum neurotoxin A, by immunostaining in a range of clinical tissues, including human dorsal root ganglion sensory neurons, peripheral nerves, the urinary bladder, and the colon. We also determined the effects of botulinum neurotoxins A and E on localization of the capsaicin receptor, TRPV1, and functional sensitivity to capsaicin stimuli in cultured human dorsal root ganglion neurons. RESULTS: Image analysis showed that SV2A immunoreactive nerve fibers were increased in injured nerves proximal to the injury (P = 0.002), and in painful neuromas (P = 0.0027); the ratio of percentage area SV2A to neurofilaments (a structural marker) was increased proximal to injury (P = 0.0022) and in neuromas (P = 0.0001), indicating increased SV2A levels in injured nerve fibers. In the urinary bladder, SV2A nerve fibers were found in detrusor muscle and associated with blood vessels, with a significant increase in idiopathic detrusor over-activity (P = 0.002) and painful bladder syndrome (P = 0.0087). Colon biopsies showed numerous SV2A-positive nerve fibers, which were increased in quiescent inflammatory bowel disease with abdominal pain (P = 0.023), but not in inflammatory bowel disease without abdominal pain (P = 0.77) or in irritable bowel syndrome (P = 0.13). In vitro studies of botulinum neurotoxin A-treated and botulinum neurotoxin E treated cultured human sensory neurons showed accumulation of cytoplasmic vesicles, neurite loss, and reduced immunofluorescence for the heat and capsaicin receptor, TRPV1. Functional effects included dose-related inhibition of capsaicin responses on calcium imaging after acute treatment with botulinum neurotoxins A and E. CONCLUSION: Differential levels of SV2A protein expression in clinical disorders may identify potential new targets for botulinum neurotoxin therapy. In vitro studies indicate that treatment with botulinum neurotoxins A and E may affect receptor expression and nociceptor function in sensory neurons. PMID- 22090804 TI - Placebo controlled, crossover validation study of oral ibuprofen and topical hydrocortisone- 21-acetate for a model of ultraviolet B radiation (UVR)-induced pain and inflammation. AB - BACKGROUND: Pain related to ultraviolet B radiation (UVR) induced sunburn is an established, simple, acute pain model. One of the major criticisms is related to the potential dermal adverse events caused by the UVR exposure. This study tried to validate the model for oral and topical drugs and to define the minimum required UVR exposure. METHODS: This subject- and observer-blinded, placebo controlled, crossover study evaluated 600 mg oral ibuprofen (IB) and topical hydrocortisone-21-acetate (HC) twice daily (bid) in 24 healthy volunteers. Treatment started immediately after irradiation and again at 12 hours, 24 hours, and 36 hours post-UVR. Assessment of hyperalgesia to heat and signs of inflammation (erythema, skin temperature) for all areas was performed after UVR and again at 6, 12, 24, 36, and 48 hours. Subjects returned within 4-11 days to the study site for the second period of the study. As in the first period, subjects received HC at one side and topical placebo on the other side, but oral treatment was crossed-over. RESULTS: The primary analysis failed to show the expected superiority of the IB-group vs the placebo group in period 1 of the study. Evaluating period 2 alone clearly showed the expected treatment effects of IB for erythema and heat pain threshold. The results were less pronounced for skin temperature. In contrast to IB vs oral placebo, there were no differences in treatment response between HC and topical placebo. UVR at all dosages induced profound erythema and reduction of heat pain threshold without causing blisters or other unexpected discomfort to the subjects. The changes were almost linear between 1 and 2 minimal erythema doses (MED), whereas the change from 2 to 3 MED was less pronounced. CONCLUSION: Use of 2 MED in upcoming studies seems to be reasonable to limit subjects' UVB exposure. The following procedural changes are suggested: Intensified training sessions before randomization to treatmentIncrease in sample size if they are crossover studiesSimplification in design (either oral or topical treatment). PMID- 22090805 TI - Functional MRI brain imaging studies using the Contact Heat Evoked Potential Stimulator (CHEPS) in a human volunteer topical capsaicin pain model. AB - Acute application of topical capsaicin produces spontaneous burning and stinging pain similar to that seen in some neuropathic states, with local hyperalgesia. Use of capsaicin applied topically or injected intradermally has been described as a model for neuropathic pain, with patterns of activation in brain regions assessed using functional magnetic resonance imaging (fMRI) and positron emission tomography. The Contact Heat Evoked Potential Stimulator (CHEPS) is a noninvasive clinically practical method of stimulating cutaneous A-delta nociceptors. In this study, topical capsaicin (1%) was applied to the left volar forearm for 15 minutes of twelve adult healthy human volunteers. fMRI scans and a visual analog pain score were recorded during CHEPS stimulation precapsaicin and postcapsaicin application. Following capsaicin application there was a significant increase in visual analog scale (mean +/- standard error of the mean; precapsaicin 26.4 +/- 5.3; postcapsaicin 48.9 +/- 6.0; P < 0.0001). fMRI demonstrated an overall increase in areas of activation, with a significant increase in the contralateral insular signal (mean +/- standard error of the mean; precapsaicin 0.434 +/- 0.03; postcapsaicin 0.561 +/- 0.07; P = 0.047). The authors of this paper recently published a study in which CHEPS-evoked A-delta cerebral potential amplitudes were found to be decreased postcapsaicin application. In patients with neuropathic pain, evoked pain and fMRI brain responses are typically increased, while A-delta evoked potential amplitudes are decreased. The protocol of recording fMRI following CHEPS stimulation after topical application of capsaicin could be combined with recording of evoked potentials to provide a simple, rapid, and robust volunteer model to develop novel drugs for neuropathic pain. PMID- 22090806 TI - Effectiveness and safety of morphine sulfate extended-release capsules in patients with chronic, moderate-to-severe pain in a primary care setting. AB - BACKGROUND: The purpose of this study was to determine the effectiveness and safety of morphine sulfate extended-release capsules among primary care patients with chronic, moderate-to-severe pain using a universal precautions approach that assessed and monitored risk for opioid misuse and abuse. METHODS: This open label, uncontrolled, multicenter, prospective study was conducted in primary care centers (n = 281) and included opioid-naive and opioid-experienced patients with either a pain score >=4 (0 = no pain, 10 = pain as bad as you can imagine), or with unacceptable side effects while taking opioids. The patients were treated with morphine sulfate extendedrelease capsules for up to four months. Patient rated pain intensity (worst, least, average) over the past 24 hours (0-10 scale), pain interference with seven activities of daily living (0 = no interference, 10 = completely interferes), and adverse events were recorded. RESULTS: Of 1487 patients who filled at least one prescription, 561 (38%) completed the study. Patients were primarily white (87%) and female (57%); 92% had pain for more than one year; and 79% were opioid-experienced. Median age was 52 years. Decreases in mean (+/- standard deviation) average pain scores (baseline 6.2 +/- 2.3) were 0.8 +/- 2.2 at visit 2 (5-14 days later), and -1.6 +/- 2.3 and -1.7 +/- 2.2 at visits 3 and 4 (spaced 3-4 weeks apart), respectively, and -1.1 +/- 2.4 at visit 5 (included patients withdrawn from the study who were no longer taking the study drug). A similar trend was observed for worst pain and least pain scores and for pain interference with activities. Fifty-one percent of the safety population patients and 81% in the completer population reported being satisfied or very satisfied with the study treatment. Most common adverse events were typical of opioids, ie, constipation (14%), nausea (11%), vomiting (5%), and somnolence (5%). CONCLUSION: The results suggest that pain outcomes improved in patients with chronic, moderate-to-severe pain receiving morphine sulfate extended-release capsules within the context of a structured universal precautions approach in the primary care setting. PMID- 22090807 TI - LaZn(12.37 (1)), a zinc-deficient variant of the NaZn(13) structure type. AB - The title compound (lanthanum dodecazinc), LaZn(12.37 (1)), is confirmed to be a nonstoichiometric (zinc-deficient) modification of the NaZn(13) structure type, in which one Zn atom (Wyckoff site 8b, site symmetry m[Formula: see text]) has a fractional site occupancy of 0.372 (11). The other Zn atom (96i, m) and the La atom (8a, 432) are fully occupied. The coordination polyhedra of the Zn atoms are distorted icosa-hedra, whereas the La atoms are surrounded by 24 Zn atoms, forming pseudo-Frank-Kasper polyhedra. Electronic structure calculations indicate that Zn-Zn bonding is much stronger than La-Zn bonding. PMID- 22090808 TI - Silver(I) diaqua-nickel(II) catena-borodiphosphate(V) hydrate, (Ag(0.57)Ni(0.22))Ni(H(2)O)(2)[BP(2)O(8)].0.67H(2)O. AB - The structure framework of the title compound, (Ag(0.57)Ni(0.22))Ni(H(2)O)(2)[BP(2)O(8)].0.67H(2)O, is the same as that of its recently published counterpart AgMg(H(2)O)(2)[BP(2)O(8)].H(2)O. In the title structure, the Ag, Ni, B and one O atom are located on special positions (sites symmetry 2). The structure consists of infinite borophosphate helical [BP(2)O(8)](3-) ribbons, built up from alternate BO(4) and PO(4) tetra-hedra arranged around the 6(5) screw axes. The vertex-sharing BO(4) and PO(4) tetra hedra form a spiral ribbon of four-membered rings in which BO(4) and PO(4) groups alternate. The ribbons are connected through slightly distorted NiO(4)(H(2)O)(2) octa-hedra, four O atoms of which belong to the phosphate groups. The resulting three-dimensional framework is characterized by hexa-gonal channels running along [001]. However, the main difference between the structures of these two compounds lies in the filling ratio of Wyckoff positions 6a and 6b in the tunnels. Indeed, in this work, the refinement of the occupancy rate of sites 6a and 6b shows that the first is occupied by water at 67% and the second is partially occupied by 56.6% of Ag and 21.6% of Ni. In the AgMg(H(2)O)(2)[BP(2)O(8)].H(2)O structure, these two sites are completely occupied by H(2)O and Ag(+), respectively. The title structure is stabilized by O-H?O hydrogen bonds between water mol-ecules and O atoms that are part of the helices. PMID- 22090809 TI - Bis{2-[(E)-(4-fluoro-benz-yl)imino-meth-yl]-6-meth-oxy-phenolato kappaN,O}nickel(II). AB - In the title compound, [Ni(C(15)H(13)FNO(2))(2)], the Ni(II) atom is tetra coordinated by two N atoms and two O atoms from two 2-[(4-fluoro-benz-yl)imino meth-yl]-6-meth-oxy-phenolate ligands in a square-planar geometry. The two N atoms and two O atoms around the Ni(II) atom are trans to each other, as the Ni(II) atom lies on an inversion centre. In the fluoro-phenyl group, five C atoms and an F atom are disordered over two sets of positions of equal occupancy. In the crystal, the complex mol-ecules are linked via inter-molecular C-H?F hydrogen bonds, forming chains along [001]. PMID- 22090810 TI - 1,1',2,2',3,3',4,4'-Octa-methyl-ferro-cenium 2,5-dibromo-4-hy-droxy-3,6 dioxocyclo-hexa-1,4-dien-1-olate. AB - In the title salt, octa-methyl-ferrocenium bromanilate, [Fe(C(9)H(13))(2)](C(6)HBr(2)O(4)), the Fe atom and the bromanilate anion lie on a mirror plane. The octa-methyl-ferrocenium cation adopts an eclipsed conformation. An intra-molecular O-H?O hydrogen bond is present in the bromanilate anion. In the crystal, the cations and anions are stacked alternately, forming a one-dimensional columnar structure along [010]. PMID- 22090811 TI - The monoclinic polymorph of dimethyl-arsinic acid. AB - The title compound, C(2)H(7)AsO(2) or [As(CH(3))(2)O(OH)], is an organic derivative of arsinic acid, and is also known by its trivial name cacodylic acid. In contrast to the first polymorph (triclinic, space group P[Formula: see text], Z = 2), the current study revealed monoclinic symmetry (space group C2/c, Z = 8) for the second polymorph. The configuration of the tetra-hedral mol-ecule shows approximate C(s) symmetry. Strong O-H?O hydrogen bonds connect the mol-ecules to infinite zigzag chains along [010], which are further connected by weak inter molecular C-H?O contacts into a three-dimensional network. PMID- 22090812 TI - catena-Poly[[bis-(1H-imidazole-kappaN)copper(II)]-MU-benzene-1,4-dicarboxyl-ato kappaO:O]. AB - In the title compound, [Cu(C(8)H(4)O(4))(C(3)H(4)N(2))(2)](n), the Cu(II) atom is four-coordinated by two carboxyl-ate O atoms from two different terephthalate ligands and two N atoms from two imidazole ligands in a slightly distorted square planar coordination environment. Each terephthalate ligand acts as a bis monodentate ligand that binds two Cu(II) atoms, thus forming two unique chains extending parallel to [110]. The imidazole ligands are attached on both sides of the chains. PMID- 22090813 TI - Potassium N-bromo-2-methyl-benzene-sulfonamidate sesquihydrate. AB - In the structure of the title compound, K(+).C(7)H(7)BrNO(2)S(-).1.5H(2)O, the K(+) ion is hepta-coordinated by three O atoms from water mol-ecules and by four sulfonyl O atoms of N-bromo-2-methyl-benzene-sulfonamide anions. The S-N distance of 1.577 (5) A is consistent with an S=N double bond. The crystal structure comprises sheets in the ac plane which are further stabilized by O-H?Br and O-H?N hydrogen bonds. PMID- 22090814 TI - 1,2-Dimethyl-1,4-diazo-niabicyclo-[2.2.2]octane tetra-chloridocuprate(II). AB - In the title compound, (C(8)H(18)N(2))[CuCl(4)], torsion angles on the ethyl-ene bridges of the 1,4-diazo-niabicyclo-[2.2.2]octane fragment are in the range 11.9 (5)-15.0 (5) degrees and the [CuCl(4)](2-) anion has a strongly distorted tetra hedral geometry. The cation is connected to the anion via three-center N-H?Cl hydrogen bonds. PMID- 22090815 TI - Dichlorido(4'-ferrocenyl-2,2':6',2''-terpyridine-kappaN,N',N'')zinc acetonitrile monosolvate. AB - The title complex, [FeZn(C(5)H(5))Cl(2)(C(20)H(14)N(3))].CH(3)CN, is composed of one Zn(II) atom, one 4'-ferrocenyl-2,2':6',2''-terpyridine (fctpy) ligand, two Cl atoms and one acetonitrile solvent mol-ecule. The Zn(II) atom is five-coordinated in a trigonal-bipyramidal geometry by the tridentate chelating fctpy ligand and two Cl atoms. PMID- 22090816 TI - Octa-butylbis[MU(2)-4-(diethyl-amino)-benzoato-kappaO:O']bis-[4-(diethyl-amino) benzoato-kappaO]di-MU(3)-oxido-tetra-tin(IV). AB - The asymmetric unit of the title complex, [Sn(4)(C(4)H(9))(8)(C(11)H(14)NO(2))(4)O(2)], consists of two crystallographically independent half-mol-ecules. The other halves are generated by crystallographic inversion centers. In each tetra-nuclear mol-ecule, both of the two independent Sn atoms are five-coordinated, with distorted trigonal bipyramidal SnC(2)O(3) geometries. One Sn atom is coordinated by two butyl groups, one O atom of the benzoate anion and two bridging O atoms, whereas the other Sn atom is coordinated by two butyl groups, two O atoms of the benzoate anions and a bridging O atom. All the butyl groups are equatorial with respect to the SnO(3) trigonal plane. Weak intra-molecular C-H?O hydrogen bonds stabilize the mol-ecular structures. In one mol-ecule, two of the butyl groups and the bridging benzoate anion are each disordered over two positions. PMID- 22090817 TI - Poly[(MU(4)-benzene-1,3,5-tricarboxyl-ato)bis-(N,N-dimethyl-formamide) cerium(III)]. AB - The asymmetric unit of the title rare earth coordination polymer, [Ce(C(9)H(3)O(6))(C(3)H(7)NO)(2)](n), contains one eight-coordinated Ce(3+) ion, one benzene-1,3,5-tricarboxyl-ate (BTC) ligand and two coordinated N,N-dimethyl formamide (DMF) mol-ecules. The Ce(3+) ion is coordinated by six O atoms from four carboxyl-ate groups of the BTC ligands and by two O atoms from two terminal DMF mol-ecules. PMID- 22090818 TI - Diammine(2,2'-bipyridine)-bis(thio-cyan-ato--kappaN)cobalt(III) diamminetetra kis(thio-cyanato--kappaN)chromate(III) aceto-nitrile disolvate. AB - The new heterometallic title complex, [Co(NCS)(2)(C(10)H(8)N(2))(NH(3))(2)][Cr(NCS)(4)(NH(3))(2)].2CH(3)CN, has been prepared using the open-air reaction of cobalt powder, Reineckes salt and 2,2' bipyridine (dpy) in acetonitrile. The crystal structure consists of discrete cationic [Co(NCS)(2)(NH(3))(2)(dpy)](+) and anionic [Cr(NCS)(4)(NH(3))(2)](-) building blocks, both with 2 symmetry, and acetonitrile solvent mol-ecules, which are linked together by N-H?N hydrogen bonds, forming extended supra-molecular chains. Furthermore, N-H?S, C-H?S and C-H?N hydrogen bonds inter-link neighbouring chains into a three-dimensional framework. The Co atom is in an elongated octa-hedral coordination environment with two N atoms from the dpy ligands and two NCS-groups in the equatorial plane and with two NH(3) mol-ecules at the axial positions. The Cr(III) ion is octa-hedraly coordinated by two NH(3) mol-ecules at the axial positions and four NCS-groups in the equatorial plane. Intensity statistics indicated non-merohedral twinning with the twin matrix [100; 0[Formula: see text]0; [Formula: see text]0[Formula: see text]]. The refined ratio of the twin components is 0.530 (1):0.470 (1). PMID- 22090819 TI - Bis[N-(2-amino-eth-yl)ethane-1,2-diamine-kappaN,N',N'']copper(II) tris [diamminetetra-kis-(thio-cyanato-kappaN)chromate(III)] thio-cyanate dimethyl sulfoxide tetra-deca-solvate monohydrate. AB - The ionic title complex, [Cu(C(4)H(13)N(3))(2)](2)[Cr(NCS)(4)(NH(3))(2)](3)(NCS).14C(2)H(6)OS.H(2)O, consists of complex [Cu(dien)(2)](2+) cations [dien is N-(2-amino-eth-yl)ethane 1,2-diamine], com-plex [Cr(NCS)(4)(NH(3))(2)](-) anions, an NCS(-) counter-anion and uncoordinated dimethyl sulfoxide (DMSO) and water solvent mol-ecules. One of the Cr atoms lies on an inversion center, while the second Cr atom and the Cu atom lie in general positions. The thio-cyanate counter-anion and water mol-ecule are disordered over two positions close to an inversion center. There are several types of hydrogen-bond inter-actions present in the title compound, which connect the complex cations and anions into bulky [Cu(2)Cr(3)] polynuclear species. The four NH(3) groups of the complex anions and six bridging DMSO O atoms link the three complex anions via hydrogen bonding into the anionic polynuclear species [Cr(NCS)(4)(NH(3))(2)](3).6DMSO. The last one is connected by four bridging DMSO O atoms with the two complex copper cations through N-H? O hydrogen bonds between the terminal NH(3) groups of the anionic polynuclear species and the NH and NH(2) groups of the dien ligand. One additional DMSO mol-ecule is connected via hydrogen bonding to one of the terminal NH(3) groups of the anionic polynuclear species. Another DMSO mol-ecule is connected via hydrogen bonding to each Cu(dien)(2)](2+) cation. PMID- 22090820 TI - [Bis(3-amino-prop-yl)amine-kappaN,N',N'']bis-(thio-cyanato-kappaN)cobalt(II). AB - The asymmetric unit of the title compound, [Co(NCS)(2)(C(6)H(17)N(3))], consists of one Co(2+) cation, two thio-cyanate anions and one bis-(3-amino-prop-yl)amine ligand, all in general positions. The cobalt cation is coordinated by five N atoms of two terminal N-bonded thio-cyanate anions and one bis-(3-amino-prop yl)amine ligand, defining a slightly distorted square-pyramidal coordination polyhedron. The mol-ecules are held together in the crystal by weak N-H?S inter actions. PMID- 22090821 TI - Dichlorido{N,N-dimethyl-N'-[1-(2-pyrid-yl)ethyl-idene]ethane-1,2-diamine kappaN,N',N''}zinc. AB - The asymmetric unit of the title compound, [ZnCl(2)(C(11)H(17)N(3))], contains two independent penta-coordinate Zn(II) complex mol-ecules. In each mol-ecule, the metal atom is coordinated by an N,N',N''-tridenate Schiff base and two Cl atoms in a distorted square-pyramidal geometry. The two mol-ecules differ little in their geometry, but more in their inter-molecular inter-actions. In the crystal, adjacent mol-ecules are connected via C-H?Cl inter-actions into a three dimensional supra-molecular structure. The network is supplemented by pi-pi inter actions formed between the aromatic rings of pairs of the symmetry-related mol ecules [centroid-centroid distances = 3.6255 (10) and 3.7073 (10) A]. The crystal lattice contains void spaces with a size of 52 A(3). PMID- 22090822 TI - [5-Chloro-2-hy-droxy-N'-(2-oxidobenzyl-idene)benzohydrazidato]dimethyl-tin(IV). AB - In the title compound, [Sn(CH(3))(2)(C(14)H(9)ClN(2)O(3))], the Sn(IV) ion is coordinated by one N and two O atoms from the tridentate 5-chloro-2-hy-droxy-N' (2-oxidobenzyl-idene)benzohydrazidate (L) ligand and two methyl groups in a distorted trigonal-bipyramidal geometry. In the ligand, the hy-droxy group is involved in an intra-molecular O-H?N hydrogen bond and the two aromatic rings form a dihedral angle of 5.5 (1) degrees . In the crystal, weak inter-molecular C H?O hydrogen bonds and pi-pi inter-actions between the aromatic rings [centroid centroid distance = 3.816 (3) A] link the mol-ecules into centrosymmetric dimers. PMID- 22090823 TI - Bis(N-benzoyl-N-phenyl-hydroxy-l-aminato-kappaO,O')dimethyl-tin(IV). AB - The Sn atom in the title compound, [Sn(CH(3))(2)(C(13)H(10)NO(2))(2)], has a highly distorted octa-hedral coordination with the equatorial plane made up of four O atoms from two N-benzoyl-N-phenyl-hydroxy-laminate ligands and the axial positions occupied by two methyl groups. The crystal structure is stabilized by van der Waals inter-actions. PMID- 22090824 TI - catena-Poly[[trimethyl-tin(IV)]-MU-3,5-difluoro-benzoato-kappaO:O']. AB - In the title compound, [Sn(CH(3))(3)(C(7)H(3)F(2)O(2))](n), the central Sn atom is coordinated by two O atoms from the anion and three methyl C atoms in a polymeric fashion owing to the presence of bidentate bridging carboxyl-ate ligands. The five-coordinate Sn atom exists in a distorted trigonal-bipyramidal geometry with the mol-ecules connected by weak C-H?F inter-moleclar inter actions, forming supra-molecular chains parallel to [010]. PMID- 22090825 TI - Poly[[MU-1,4-bis-(1H-imidazol-4-yl)benzene-kappaN:N](MU-5-methyl-isophthalato kappaO:O)cobalt(II)]. AB - In the title coordination polymer, [Co(C(9)H(6)O(4))(C(12)H(10)N(4))](n), the Co(II) atom is four-coordinated by two O atoms from two different 5-methyl isophthalate bivalent anions and two N atoms from two different 1,4-bis-(1H imidazol-4-yl)benzene ligands, forming a four-coordinated tetra-hedral coordination geometry. Each 5-methyl-isophthalate ligand acts as a MU(2)-bridge, linking two Co(II) atoms and forming chains which are further linked by 1,4-bis (1H-imidazol-4-yl)benzene ligands into a two-dimensional network parallel to ([Formula: see text]01). These planes are, in turn, linked by two inter-molecular N-H?O inter-actions, forming a three-dimensional structure. Weak C-H?O hydrogen bonds are also present in the structure. PMID- 22090826 TI - A tetra-gonal polymorph of bis-[hydro-tris-(pyrazol-1-yl)borato]iron(II). AB - The title compound, [Fe(C(9)H(10)BN(6))(2)], is a polymorph of a compound reported previously [Oliver et al. (1980 ?). Inorg. Chem.19, 165-168]. In the previous report, the compound crystallized in the monoclinic space group P2(1)/c (Z = 4), whereas the crystal symmetry of the compound reported here is tetra gonal (P4(2)/ncm, Z = 4). The mol-ecular structure is comprised of two hydro-tris (1-pyrazol-yl)borate ligands (Tp(-)) and a central Fe(II) ion, which is coordinated by six pyrazole N atoms from two two Tp(-) ligands, yielding a distorted bipyramidal FeN(6) geometry. The complete molecule exhibits symmetry 2/m. PMID- 22090827 TI - Bis(acetohydroxamato-kappaO,O')diphenyl-tin(IV). AB - The complex mol-ecule of the title compound, [Sn(C(6)H(5))(2)(C(2)H(4)NO(2))(2)], has crystallographically imposed twofold symmetry. The Sn atom is coordinated by four O atoms from two acetohydroxamate ligands and by two C atoms from phenyl groups in a distorted octa-hedral geometry. In the crystal, mol-ecules are connected by N-H?O hydrogen-bonding inter-actions, forming a chain structure along the c axis. PMID- 22090828 TI - Bis{4-bromo-2-[(2-hy-droxy-eth-yl)imino-meth-yl]phenolato-kappaO,N,O'}cadmium. AB - The centrosymmetric title compound, [Cd(C(9)H(9)BrNO(2))(2)], was obtained by the reaction of 5-bromo-salicyl-aldehyde, 2-amino-ethanol and cadmium nitrate in ethanol. The Cd atom, located on an inversion centre, is hexa-coordinated by two Schiff base ligands in an octa-hedral coordination through the phenolate O atom, the imine N atom and the hy-droxy O atoms. In the crystal, mol-ecules are linked through inter-molecular O-H?O hydrogen bonds, forming chains along the b axis. PMID- 22090829 TI - catena-Poly[[tetra-aqua-manganese(II)]-MU-5-carboxyl-ato-1-carboxyl-atomethyl-2 oxidopyridinium-kappaO:O]. AB - In the title coordination polymer, [Mn(C(8)H(5)NO(5))(H(2)O)(4)](n), the Mn(II) atom is coordinated by two carboxyl-ate O atoms from two 5-carboxyl-ato-1 carboxyl-atomethyl-2-oxidopyridinium (L(2-)) ligands and by four water mol-ecules in a distorted octa-hedral geometry. The L(2-) ligands bridge the Mn atoms into an infinite chain motif along [100]; the chains are further inter-linked by O-H?O hydrogen bonds into a three-dimensional supra-molecular net. PMID- 22090830 TI - catena-Poly[[diiodidocadmium]-MU-[4,4'-(2,3,5,6-tetra-methyl-1,4-phenyl-ene)bis (methyl-ene)]bis-(3,5-dimethyl-1H-pyrazole)-kappaN:N]. AB - The heterocylic ligand of the polymeric title compound, [CdI(2)(C(22)H(30)N(4))], links two adjacent CdI(2) units, forming a chain running parallel to [[Formula: see text]01]. The Cd(II) atom is located on a twofold rotation axis and shows a distorted tetra-hedral CdI(2)N(2) coordination. The mid-point of the benzene ring of the ligand lies on a center of inversion. There are no classical hydrogen bonding inter-actions present. PMID- 22090831 TI - Bis{N-methyl-N'-[1-(pyridin-2-yl)ethyl-idene]ethane-1,2-diamine}-zinc bis (perchlorate). AB - The title mononuclear zinc(II) complex, [Zn(C(10)H(15)N(3))(2)](ClO(4))(2), was obtained by the reaction of 2-acetyl-pyridine, N-methyl-ethane-1,2-diamine and zinc perchlorate in methanol. The asymmetric unit of the complex contains two independent [Zn(C(10)H(15)N(3))(2)](2+) cations and four perchlorate anions. The Zn(II) atom in each complex cation is six-coordinated by two pyridine N, two imine N and two amine N atoms from two N-methyl-N'-[1-(pyridin-2-yl)ethyl idene]ethane-1,2-diamine Schiff base ligands in a distorted octa-hedral geometry. The pyridine rings in each of the complex cations are approximately perpendicular to each other, making dihedral angles of 88.4 (3) and 87.9 (3) degrees . The perchlorate anions are linked to the complex cations through N-H?O hydrogen bonds. PMID- 22090832 TI - Poly[(MU-3,5-dinitro-benzoato)(MU-3,5-dinitro-benzoic acid)rubidium]. AB - The asymmetric unit of the title compound, [Rb(C(7)H(3)N(2)O(6))(C(7)H(4)N(2)O(6))](n), comprises an Rb(+) cation, a 3,5 dinitro-benzoate anion and a 3,5-dinitro-benzoic acid ligand. The Rb(+) cation is nine-coordinated by O atoms from four 3,5-dinitro-benzoate anions and three neutral 3,5-dinitro-benzoic acid ligands. The metal atom is firstly linked by four bridging carboxyl groups, forming a binuclear motif, which is further linked by the nitro groups into a two-dimensional framework along the [110] direction. A short O-H?O hydrogen bond between two adjacent carboxy/carboxylate groups occurs. PMID- 22090833 TI - Di-MU-acetato-bis-(dimethyl-formamide)-penta-kis-(MU-N,2-dioxidobenzene-1-car boximidato)tetra-kis-(1-ethyl-imidazole)-penta-manganese(III)-manganese(II) diethyl ether-dimethyl-foramide-methanol-water (1/1/1/1/0.12). AB - The title compound [Mn(6)(C(7)H(4)NO(3))(5)(CH(3)CO(2))(2)(C(5)H(8)N(2))(4)(C(3)H(7)NO)(2)].(C(2)H(5 )(2)O.C(3)H(7)NO.CH(3)OH.0.12H(2)O, abbreviated as Mn(II)(OAc)(2)[15 MC(MnIII(N)shi)-5](EtIm)4(DMF)2.diethyl ether.DMF.MeOH.0.12H(2)O (where (-)OAc is acetate, MC is metallacrown, shi(3-) is salicylhydroximate, EtIM is n ethylimidazole, DMF is N,N-dimethylformamide, and MeOH is methanol) contains five Mn(III) ions as members of the metallacrown ring and an Mn(II) ion bound in the central cavity. The central Mn(II) ion is seven-coordinate with a distorted face capped trigonal-prismatic geometry. The five Mn(III) ions of the metallacrown ring are six-coordinate with distorted octa-hedral geometries. The configuration of the Mn(III) ions about the metallacrown ring follow a DeltaLambdaDeltaPP pattern, with P representing planar. The four 1-ethyl-imidazole ligands are bound to four different Mn(III) ions. A diethyl ether solvent mol-ecule was found to be disordered over two mutually exclusive sites with an occupancy ratio of 0.568 (7):0.432 (7). A methanol solvent mol-ecule was found to be disordered over two mutually exclusive sites by being hydrogen bonded either to a dimethyl-formamide solvent mol-ecule (major occupancy component) or to an O atom of the main mol ecule (minor occupancy component). The occupancy ratio refined to 0.678 (11):0.322 (11). Associated with the minor component is a partially occupied water mol-ecule [total occupancy 0.124 (15)]. PMID- 22090834 TI - Aqua-(4-carb-oxy-pyridine-2,6-dicarboxyl-ato-kappaO,N,O)(1,10-phenanthroline kappaN,N')nickel(II). AB - The title compound, [Ni(C(8)H(3)NO(6))(C(12)H(8)N(2))(H(2)O)], contains an Ni(II) ion, a 1,10-phenanthroline (phen) ligand, a 4-carb-oxy-pyridine-2,6-dicarboxyl ate (Hptc(2-)) anion and a coordinated water mol-ecule. The Ni(II) atom exhibits a distorted octa-hedral N(3)O(3) environment. O-H?O hydrogen bonding between coordinated water and carboxyl-ate O atoms, as well as pi-pi stacking inter actions [inter-planar distances between phen rings = 3.293 (2) A] lead to a supermolecular assembly. PMID- 22090835 TI - Aqua-chloridobis(2-{[3-(morpholin-4-yl)prop-yl]imino-meth yl}phenolato)manganese(III) monohydrate. AB - In the title compound, [Mn(C(14)H(19)N(2)O(2))(2)Cl(H(2)O)].H(2)O, the Mn(III) atom is N,O-chelated by two monoanionic Schiff bases, forming two six-membered chelate rings. One Cl atom and one water mol-ecule in trans positions complete a distorted octa-hedral geometry around the metal atom. In the crystal, the complex mol-ecules and the uncoordinated water mol-ecules are connected via O-H?N, O-H?O and O-H?Cl hydrogen bonds into layers parallel to the ac plane and these are consolidated by C-H?pi inter-actions. The layers are further linked into a three dimensional network through C-H?O inter-actions. PMID- 22090836 TI - N,N'-Dimethyl-ethylenediammonium dioxalatocuprate(II). AB - The asymmetric unit of the title salt, (C(4)H(14)N(2))[Cu(C(2)O(4))(2)], consists of one complex anion and two cationic half-mol-ecules, the other halves being generated by inversion symmetry. The Cu(II) atom in the anion is coordinated by two bidentate oxalate ligands in a distorted square-planar geometry. Inter molecular hydrogen bonds, involving the NH groups as donors and O atoms as acceptors, are observed, which lead to the formation of a three-dimensional network structure. PMID- 22090837 TI - Poly[di-MU-aqua-bis-(MU-2-amino-4-nitro-benzoato)dicaesium]. AB - In the structure of title compound, [Cs(2)(C(7)H(5)N(2)O(4))(2)(H(2)O)(2)](n), the asymmetric unit contains two independent Cs atoms comprising different coordination polyhedra. One is nine-coordinate, the other seven-coordinate, both having irregular configurations. The CsO(9) coordination polyhedron comprises O atom donors from three bridging water mol-ecules, one of which is doubly bridging, three from carboxyl-ate groups, and three from nitro groups, of which two are bidentate chelate bridging. The CsO(6)N coordination polyhedron comprises the two bridging water mol-ecules, one amine N-atom donor, one carboxyl-ate O atom donor and four O-atom donors from nitro groups (two from the chelate bridges). The extension of the dimeric unit gives a three-dimensional polymeric structure, which is stabilized by both intra- and inter-molecular amine N-H?O and water O-H?O hydrogen bonds to carboxyl-ate O-atom acceptors, as well as inter ring pi-pi inter-actions [minimum ring centroid-centroid separation = 3.4172 (15) A]. PMID- 22090838 TI - Bis(2-amino-pyrazine-kappaN)dichlorido-zinc. AB - In the title adduct, [ZnCl(2)(C(4)H(5)N(3))(2)], the Zn(II) atom lies on a twofold rotation axis that relates one Cl atom to the other as well as one 2 amino-pyrazine ligand to the other; the coordination geometry is a distorted tetra-hedron. In the crystal, adjacent mol-ecules are linked by N-H?N hydrogen bonds across the center of inversion, generating a chain; neighboring chains are linked by N-H?Cl hydrogen bonds, forming a three-dimensional network. PMID- 22090839 TI - catena-Poly[[[dichloridomercury(II)]-MU-1,4-bis-(3-pyridyl-amino-meth-yl)benzene kappaN:N'] N,N-dimethyl-formamide monosolvate]. AB - The crystal structure of the polymeric title compound, {[HgCl(2)(C(18)H(18)N(4))].C(3)H(7)NO}(n), features an N-heterocyclic ligand which links adjacent HgCl(2) units into a helical chain running along the b axis. The coordination geometry of the Hg(II) atom is a distorted tetra-hedron. The dimethyl-formamide mol-ecule is disordered over two positions in a 1:1 ratio, and is linked to the complex mol-ecules via N-H?O hydrogen bonds. PMID- 22090840 TI - trans-Diaqua-bis-[2,5-bis-(pyridin-2-yl)-1,3,4-thia-diazole]nickel(II) bis-(tetra fluoridoborate). AB - The bidentate 1,3,4-thia-diazole ligand, namely, 2,5-bis-(2-pyrid-yl)-1,3,4-thia diazole (denoted L), untested as a polydentate ligand, has been found to form the monomeric title complex, [Ni(C(12)H(8)N(4)S)(2)(H(2)O)(2)](BF(4))(2). The complex shows an octa-hedral environment of the nickel cation in which the Ni(2+) ion is located on a center of symmetry, linked to two ligands and two water molecules. In this 1:2 complex (one metal for two organic ligands) each thia-diazole ligand uses one pyridyl and one thia-diazole N atom for chelate binding. In the second pyridyl substituent, the N atom is oriented towards the same direction as the S atom of the 1,3,4-thiadiazole ring. The mean plane of the thia-diazole and pyridyl rings linked to the nickel cation forms a dihedral angle with the other pyridine ring of 18.63 (8) degrees . The tetra-fluorido-borate ions can be regarded as free anions in the crystal lattice. Nevertheless, they are involved in an infinite two-dimensional network parallel to ([Formula: see text]01) through O-H?F hydrogen bonds. PMID- 22090841 TI - Poly[[(MU(2)-acetato-kappaO,O':O')aqua-bis-(MU(3)-isonicotinato kappaO:O':N)samarium(III)silver(I)] perchlorate]. AB - The title compound, {[AgSm(C(6)H(4)NO(2))(2)(CH(3)CO(2))(H(2)O)]ClO(4)}(n), is a three-dimensional heterobimetallic complex constructed from a repeating dimeric unit. Only half of the dimeric moiety is found in the asymmetric unit; the unit cell is completed by crystallographic inversion symmetry. The Sm(III) ion is eight-coordinated by four O atoms of four different isonicotinate ligands, three O atoms of two different acetate ligands, and one O atom of a water mol-ecule. The two-coordinate Ag(I) ion is bonded to two N atoms of two different isonicotinate anions, thereby connecting the disamarium units. In addition, the isonicotinate ligands also act as bridging ligands, generating a three dimensional network. The coordinated water mol-ecules link the carboxyl-ate group and acetate ligands by O-H?O hydrogen bonding. Another O-H?O hydrogen bond is observed in the crystal structure. The perchlorate ion is disordered over two sites with site-occupancy factors of 0.560 (11) and 0.440 (11), whereas the methyl group of the acetate ligand is disordered over two sites with site occupancy factors of 0.53 (5) and 0.47 (5). PMID- 22090842 TI - Bis(4-methyl-morpholin-4-ium) tetra-bromidozincate(II). AB - The title compound, (C(5)H(12)NO)(2)[ZnBr(4)], was synthesized by hydro-thermal reaction of ZnBr(2) with 4-methyl-morpholine in a HBr/distilled water solution. Each of the two independent cations exhibits a chair conformation; the anion deviates slightly from an tetrahedral configuration. The Zn-Br distances in the anion are in the range of 2.3996 (9)-2.4247 (9) A. All of the amine H atoms are involved in bifurcated inter-molecular N-H?Br hydrogen bonds, building up a trimer. PMID- 22090843 TI - catena-Poly[[[bis-(4-ethyl-benzoato-kappaO,O')lead(II)]-MU-nicotinamide-kappaN:O] monohydrate]. AB - In the crystal structure of the polymeric title compound, {[Pb(C(9)H(9)O(2))(2)(C(6)H(6)N(2)O)].H(2)O}(n), the six-coordinate Pb(II) ion is chelated by two 4-ethyl-benzoate (PEB) anions and is bridged by two nicotinamide (NA) ligands, forming a polymeric chain running along the b axis. The carboxyl ate groups of the PEB ions are twisted away from the attached benzene rings by 4.0 (6) and 13.3 (5) degrees . The two benzene rings of the PEB ions bonded to the same metal ion are oriented at a dihedral angle of 87.4 (3) degrees . In the polymeric chain, the NA ligand is linked to one of the carboxyl-ate groups via N H?O hydrogen bonding. In the crystal, adjacent polymeric chains inter-act via N H?O and weak C-H?O hydrogen bonds; and the lattice water mol-ecule links with the polymeric chains via N-H?O and O-H?O hydrogen bonding. pi-pi stacking between the benzene and the pyridine rings [centroid-centroid distance = 3.805 (5) A] and weak C-H?pi inter-actions are also observed in the crystal structure. PMID- 22090844 TI - Bis[2,6-bis-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine]di-MU(3)-iodido-diiodidotetra copper(I). AB - In the title centrosymmetric tetra-nuclear complex, [Cu(4)I(4)(C(15)H(17)N(5))(2)], the two distinct Cu(I) atoms adopt similar tetra hedral arrangements, each being ligated by two I atoms, and two N atoms from one 2,6-bis-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine ligand. In the crystal, there are no hydrogen bonds present, and only very weak pi-pi inter-actions are observed [centroid-centroid distance = 3.985 (4) A], which connect neighbouring tetra nuclear units into a chain motif along the b axis. PMID- 22090845 TI - Poly[tetra-deca-aqua-tetra-kis-(MU(3)-1H-imidazole-4,5-dicarboxyl-ato)tetra-MU(3) sulfato-cobalt(II)hexa-gadolinium(III)]. AB - The asymmetric unit of the title compound, [CoGd(6)(C(5)H(2)N(2)O(4))(4)(SO(4))(6)(H(2)O)(14)](n), contains a Co(II) ion (site symmetry [Formula: see text]), three Gd(III) ions, two imidazole-4,5 dicarboxyl-ate ligands, three SO(4) (2-) anions, and seven coordinated water mol ecules. The Co(II) ion is six-coordinated by two O atoms from water mol-ecules, two O atoms and two N atoms from two imidazole-4,5-dicarboxyl-ate ligands, giving a slightly distorted octa-hedral geometry. The Gd(III) ions exhibit three types of coordination environments. One Gd ion is eight-coordinated in a bicapped trigonal-prismatic geometry by four O atoms from two imidazole-4,5-dicarboxyl-ate ligands, two O atoms from two SO(4) (2-) anions and two coordinated water mol ecules. The other Gd ions are nine-coordinated in a tricapped trigonal-prismatic geometry; one of these Gd ions is bonded to four O atoms from two imidazole-4,5 dicarboxyl-ate ligands, three O atoms from three SO(4) (2-) anions and two water O atoms and the other Gd ion is coordinated by one O atom and one N atom from one imidazole-4, 5-dicarboxyl-ate ligand, five O atoms from three SO(4) (2-) anions as well as two coordinated water mol-ecules. These metal coordination units are connected by bridging imidazole-4,5-dicarboxyl-ate and sulfate ligands, generating a three-dimensional network. The crystal structure is further stabilized by N-H?O, O-H?O, and C-H?O hydrogen-bonding inter-actions between water mol-ecules, SO(4) (2-) anions, and imidazole-4,5-dicarboxyl-ate ligands. PMID- 22090846 TI - [2-(1H-Benzimidazol-2-yl-kappaN)aniline-kappaN]dichloridozinc. AB - In the title benzimidazole mononuclear complex, [ZnCl(2)(C(13)H(11)N(3))], the Zn(II) ion is four-coordinated in a distorted tetra-hedral geometry by an imidazole N, an amino N and two Cl atoms. The dihedral angle between the benzimidazole and benzene rings is 9.57 (1) degrees . In the crystal, mol-ecules are linked by weak N-H?Cl hydrogen bonds into layers parallel to the bc plane. pi pi inter-actions with centroid-centroid distances in the range 3.4452 (8)-3.8074 (8) A are also observed. PMID- 22090847 TI - Bis(O-n-butyl dithio-carbonato-kappaS,S')bis-(pyridine-kappaN)manganese(II). AB - The structure of the title manganese complex, [Mn(C(5)H(9)OS(2))(2)(C(5)H(5)N)(2)] or [Mn(S(2)CO-n-Bu)(2)(C(5)H(5)N)(2)], consists of discrete monomeric entities with Mn(2+) ions located on centres of inversion. The metal atom is coordinated by a six-coordinate trans-N(2)S(4) donor set with the pyridyl N atoms located in the apical positions. The observed slight deviations from octa-hedral geometry are caused by the bite angle of the bidentate kappa(2)-S(2)CO-n-Bu ligands [69.48 (1) degrees ]. The O(CH(2))(3)(CH(3)) chains of the O-n-butyl dithio-carbonate units are disordered over two sets of sites with an occupancy ratio of 0.589 (2):0.411 (2). PMID- 22090848 TI - catena-Poly[[diaqua-bis-(3-methyl-pyridine-kappaN)cobalt(II)]-MU-sulfato kappaO:O']. AB - The environment of the Co(II) ion in the title compound, [Co(SO(4))(C(6)H(7)N)(2)(H(2)O)(2)](n), exhibits an octa-hedral configuration with the two 3-methyl-pyridine ligands lying in cis positions with respect to each other and trans to the two coordinated water mol-ecules. The axial positions are occupied by O atoms of the sulfate ions. Co and S atoms occupy special positions (twofold axis, Wyckoff position 4c). Neighboring Co(II) ions are covalently connected with each other through the sulfate ions, thus creating infinite polymeric chains that run along the c axis. The water mol-ecules are connected with neighboring sulfate ions through strong O-H?O hydrogen bonds. Intra-molecular hydrogen bonds parallel to the propagation direction of the chains stabilize the polymeric chains, and inter-molecular hydrogen bonds between chains connect neighboring chains with each other, thus leading to polymeric double chains. PMID- 22090849 TI - Poly[aqua-bis-[MU(3)-4-(3-pyrid-yl)pyrimidine-2-sulfonato-kappaN:N,O:O][MU(2)-4 (3-pyrid-yl)pyrimidine-2-sulfonato-kappaN:N,O]tris-ilver(I)]. AB - In the crystal structure of the title compound, [Ag(3)(C(9)H(6)N(3)O(3)S)(3)(H(2)O)(2)](n), the mol-ecules are linked into three decked polymeric zigzag chains propagating in [100]. On the middle deck, the Ag atom is five-coordinated by three O atoms from three 4-(3-pyrid-yl)pyrimidine-2 sulfonate (L) ligands, one of which lies on a mirror plane with the sulfonate group disordered over two orientations in a 1:1 ratio, and two N atoms from two L ligands, which lie on the same mirror plane. On the upper and lower decks, the Ag atom is four-coordinated by an aqua ligand, one O and two N atoms from two L ligands with the pyridyl and pyrimidine rings twisted at 19.8 (2) degrees . In the polymeric chain, there are pi-pi inter-actions between six-membered rings of L ligands from different decks with centroid-centroid distances of 3.621 (7) and 3.721 (3) A. In the crystal, inter-molecular O-H?O hydrogen bonds link further these three-decked chains into layers parallel to (010). PMID- 22090850 TI - Dimeric (2-cyano-phenolato-kappaO){2,2'-[ethyl-enebis(nitrilo-methyl idyne)]diphenolato-kappaO,N,N',O'}manganese(III) monohydrate. AB - The molecules of the title compound, [Mn(C(7)H(4)NO)(C(16)H(14)N(2)O(2))].H(2)O, form dimers in the solid state across a crystallographic inversion center. The bridging Mn(2)O(2) group is built of phen-oxy groups, and is asymmetric, with an Mn-O distances of 1.9002 (13) and 2.6236 (14) A. A substantial cavity between the two Mn atoms [Mn?Mn = 3.5082 (4) A] is produced by the formation of the dimer. In the crystal, an extended network of O-H?O hydrogen-bonding inter-actions stabil izes the structure. PMID- 22090851 TI - Dipotassium disulfanilamidate trihydrate. AB - The asymmetric unit of the title compound, 2K(+).2C(6)H(7)N(2)O(2)S(-).3H(2)O, consists of two potassium cations located on mirror planes, one sulfanilamidate anion in a general position and one and a half mol-ecules of water, one of which is also located on a mirror plane. One potassium cation is seven-coordinated by six sulfonyl O atoms and one water mol-ecule, whereas the other is surrounded by six water O atoms and two sulfonyl O atoms. In the crystal structure, the components are connected into polymeric sheets in the bc plane. The two dimensional structure is consolidated by N-H?O, O-H?O, O-H?N and C-H?pi inter actions. The layers are further linked into a three-dimensional network via N H?O, N-H?N and O-H?N hydrogen bonds. PMID- 22090852 TI - Tetra-aqua-bis-[4-(4H-1,2,4-triazol-4-yl)benzoato-kappaN]manganese(II) deca hydrate. AB - In the title compound, [Mn(C(9)H(6)N(3)O(2))(2)(H(2)O)(4)].10H(2)O, the Mn(II) ion is coordinated by two N atoms from two 4-(4H-1,2,4-triazol-4-yl)benzoate ligands and four water mol-ecules in a distorted octa-hedral geometry. The Mn(II) ion and two coordinated water mol-ecules lie on a twofold rotation axis. The water mol-ecules are involved in O-H?N and O-H?O hydrogen bonds with the triazole N atoms and carboxyl-ate O atoms, yielding a three-dimensional supra-molecular network. pi-pi inter-actions between the benzene rings [centroid-centroid distance = 3.836 (9) A] are observed. PMID- 22090853 TI - {4,6-Bis[(E)-1-methyl-2-(pyridin-2-yl-methyl-idene-kappaN)hydrazinyl kappaN]pyrimidine-kappaN}dichloridocopper(II) methanol disolvate monohydrate. AB - The title compound, [CuCl(2)(C(18)H(18)N(8))].2CH(3)OH.H(2)O, contains a penta coordinated Cu(II) atom bonded to the tridentate 4,6-bis-[(E)-1-methyl-2-(pyridin 2-yl-methyl-idene)hydrazin-yl]pyrimidine ligand and two Cl atoms. The geometry around the Cu(II) atom is distorted square-pyramidal. The mol-ecules pack in the crystal structure via O-H?Cl, O-H?N, C-H?Cl and C-H?O hydrogen bonds, C-H?pi and pi-pi inter-actions [centroid-centroid distances of the pyrimidine-pyridine and pyridine-pyridine inter-actions are 3.750 (3) and 3.850 (3) A, respectively], forming sheet-like assemblies. PMID- 22090854 TI - Electrostatic repulsion between the cations of (1-methyl-1H-imidazole kappaN)(2,2':6',2''-terpyridine-kappaN,N',N'')platinum(II) perchlorate nitro methane monosolvate prevents Pt?Pt inter-actions. AB - The reaction between [Pt(terpy)Cl].2H(2)O (terpy = 2',2'':6',2''-terpyridine) and 1-methyl-imidazole (MIm) in the presence of two equivalents of AgClO(4) in nitro methane yields the title compound, [Pt(C(15)H(11)N(3))(C(4)H(6)N(2))](ClO(4))(2).CH(3)NO(2). The dicationic complexes are arranged in a staggered configuration. The torsion angle subtended by the 1-methyl-imidazole ring relative to the terpyridine ring is 114.9 (5) degrees . Inter-molecular C-H?O inter-actions between the perchlorate anions and the H atoms of the terpy ligand are observed. Consideration of related phenyl bipyridyl complexes of platinum(II), which are monocationic, leads to the conclusion that the electrostatic repulsion between the dicationic chelates prevents the formation of Pt?Pt inter-actions. These inter-actions are a common feature associated with the monocationic species. PMID- 22090855 TI - (2,3,7,8,12,13,17,18-Octa-ethyl-5-phenyl-porphyrinato)platinum(II). AB - The title compound, [Pt(C(42)H(48)N(4))], was obtained through metallation of the corresponding free base with PtCl(2), followed by crystallization from methyl-ene chloride/methanol. The mol-ecule exhibits an almost planar macrocycle with an average deviation of the 24 macrocyclic atoms from their least-squares plane (Delta24) of 0.04 A and an average Pt-N bond length of 2.022 A. Despite the unsymmetrical substitution pattern, there is no significant difference between distortion of the geometry at the phenyl substituted meso position and those of unsubstituted meso positions. PMID- 22090856 TI - Tetra-aqua-{1-[(1H-1,2,3-benzotriazol-1-yl)meth-yl]-1H-1,2,4-triazole}sulfato cobalt(II) dihydrate. AB - In the title complex, [Co(SO(4))(C(9)H(8)N(6))(H(2)O)(4)].2H(2)O, the Co(II) ion is six-coordinated by one N atom from a 1H-1,2,3-benzotriazol-1-yl)meth-yl]-1H 1,2,4-triazole ligand, one O atom from a monodentate sulfate ligand and four water mol-ecules in a slightly distorted octa-hedral geometry. The sulfate ligand is rotationally disordered over two sets of sites with refined occupancies of 0.662 (15) and 0.338 (15). In the crystal, complex mol-ecules and solvent water mol-ecules are linked through inter-molecular O-H?O and O-H?N hydrogen bonds into a three-dimensional network. PMID- 22090857 TI - Homopiperazine-1,4-diium bis-[hexa-aqua-cobalt(II)] tris-ulfate. AB - In the title compound, (C(5)H(14)N(2))[Co(H(2)O)(6)](2)(SO(4))(3), the cationic framework is built up of mixed organic-inorganic fragments, namely [Co(H(2)O)(6)](2+) and [C(5)H(14)N(2)](2+). The [Co(H(2)O)(6)](2+) cations form unconnected octa-hedra. Sulfate anions inter-calated between cationic species connect them via N-H?O and O-H?O hydrogen bonds and electrostatic inter-actions. PMID- 22090858 TI - Tetra-kis[MU-1,4-bis-(4,5-dihydro-1,3-oxazol-2-yl)benzene-kappaN:N']tetra-kis-(MU methano-lato-kappaO:O)bis-(MU-perchlorato-kappaO:O')tetra-copper(II) bis (perchlorate). AB - The title tetra-nuclear Cu(II) complex, [Cu(4)(C(12)H(12)N(2)O(2))(4)(CH(3)O)(4)(ClO(4))(2)](ClO(4))(2), is located around an inversion center. Each Cu(II) atom is coordinated by two cis-O atoms from two bridging methano-late anions and two cis-N atoms from two bridging 1,4 bis-(4,5-dihydro-1,3-oxazol-2-yl)benzene (L) ligands in the basal plane, and is further coordinated by one O atom of the bridging perchlorate anion, forming a distorted square-pyramidal geometry. The Cu?Cu separations in the recta-ngular core are 2.9878 (11) and 6.974 (1) A. In the asymmetric unit, there are two L ligands with a syn conformation. In one L ligand, the dihedral angles between the central benzene ring and the terminal 4,5-dihydro-1,3-oxazol-2-yl mean planes are 22.1 (4) and 33.1 (4) degrees , and in the other L ligand the corresponding dihedral angles are 29.3 (4) and 29.9 (4) degrees . The uncoordinated perchlorate anion is linked with the complex mol-ecules via weak C-H?O hydrogen bonds. PMID- 22090859 TI - catena-Poly[(MU-2-amino-1,3,4-thia-diazole-kappaN:N)di-MU-chlorido-cadmium]. AB - In the title coordination polymer, [CdCl(2)(C(2)H(3)N(3)S)](n), the Cd(II) cation is coordinated by four Cl(-) anions and two N atoms from two trans 2-amino-1,3,4 thia-diazole (L) ligands in a distorted octa-hedral geometry. The L ligand and Cl(-) anions bridge adjacent Cd cations, forming a polymeric chain along the b axis; the separation between adjacent Cd cations is 3.619 (1) A. In the crystal, the polymeric chains are inter-linking through N-H?Cl hydrogen bonds between the L ligands and Cl(-) anions. PMID- 22090860 TI - Poly[[MU(2)-1,4-bis-(4,5-dihydro-1,3-oxazol-2-yl)benzene-kappaN:N']di-MU(2) chlorido-cadmium]. AB - In the title coordination polymer, [CdCl(2)(C(12)H(12)N(2)O(2))](n), the Cd(II) ion, situated on an inversion center, is coordinated by four bridging Cl atoms and two N atoms from two 1,4-bis-(4,5-dihydro-1,3--oxazol-2-yl)benzene (L) ligands in a distorted octa-hedral geometry. Each L ligand also lies across an inversion center and bridges two Cd(II) ions, forming infinite two-dimensional recta-ngular layers running parallel to (010). PMID- 22090861 TI - (E)-N-(Ferrocenyl-methyl-idene)(pyridin-3-yl)methanamine. AB - In the title compound, [Fe(C(5)H(5))(C(12)H(11)N(2))], the cyclo-penta-dienyl rings are present in an eclipsed conformation. The imine is E-configured. In the crystal, C-H?N inter-actions involving both N atoms connect the mol-ecules into two undulating sheets perpendicular to the b axis. The centroid-centroid distance between the two aromatic systems in the ferrocenyl moiety is 3.2928 (18) A. A C H?pi inter-action is also present. PMID- 22090862 TI - Dichlorido[2-({[3-(cyclo-hexyl-aza-nium-yl)prop-yl]imino}-meth-yl)-5-meth-oxy phenolate]zinc. AB - The title mononuclear zinc complex, [ZnCl(2)(C(17)H(26)N(2)O(2))], was obtained by the reaction of 2-hy-droxy-4-meth-oxy-benzaldehyde, N-cyclo-hexyl-propane-1,3 diamine and zinc chloride in methanol. The Zn(II) atom is four-coordinated by the phenolate O atom and imine N atom of the bidentate zwitterionic Schiff base ligand 2-{[3-(cyclo-hexyl-amino)-prop-yl]imino-meth-yl}-5-meth-oxy-phenol, and by two chloride ions, generating a distorted ZnONCl(2) tetra-hedral geometry. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds, forming chains along the c-axis direction. PMID- 22090863 TI - Ferrocenyl-phospho-nic acid. AB - In the title compound, [Fe(C(5)H(5))(C(5)H(6)O(3)P)], the phosphate group is bonded to the ferrocene unit with a P-C bond length of 1.749 (3) A. In the crystal, six ferrocenyl-phospho-nic acid mol-ecules are connected by 12 strong inter-molecular O-H?O hydrogen bonds, leading to the formation of a highly distorted octa-hedral cage. The volume of the octa-hedral cage is about 270 A(3). PMID- 22090864 TI - Poly[MU(4)-glutarato-di-MU(3)-glutarato-bis-(1,10-phenanthroline)diyttrium(III)]. AB - In the title complex, [Y(2)(C(5)H(6)O(4))(3)(C(12)H(8)N(2))(2)](n), three glutarate groups and two 1,10-phenanthroline mol-ecules surround the two Y(III) ions. Both Y(III) ions are coordinated by two N atoms from the 1,10 phenanthroline, seven O atoms from five glutarate groups in a distorted tricapped trigonal-prismatic geometry. The Y(III) ions are bridged by glutarate ligands in three modes, forming a layered, polymeric structure. The resulting layers are assembled by pi-pi stacking inter-actions [centroid-centroid distances = 3.740 (3) and 3.571 (3) A] into a three-dimensional supra-molecular architecture. PMID- 22090865 TI - Tetra-MU-acetato-bis-[(1,3-benzothia-zole)copper(II)](Cu-Cu). AB - The title compound, [Cu(2)(CH(3)CO(2))(4)(C(7)H(5)NS)(2)] or [(C(7)H(5)NS)Cu](2)(MU-O(2)CCH(3))(4), crystallizes with one mol-ecule per unit cell. The coordination number of copper is six with four basal O atoms, one axial N atom and one axial Cu atom. Four acetate ligands act as bidentate linker and connect two Cu atoms, with a crystallographic inversion center located at the mid point of the Cu-Cu bond. The acetate ligands form slightly distorted square planes around each metal ion, while the copper ions are displaced by 0.2089 (4) A from these planes towards the N atoms. Thus, the Cu-Cu distance is elongated to 2.6378 (7) A, compared with the 2.2180 (7) A distance between the two basal planes. The angle between the basal plane and the Cu-N bond is 4.84 (6) degrees . PMID- 22090866 TI - Tetra-kis(2-amino-4-methyl-pyridinium) cyclo-tetra-MU(2)-oxido-tetra-kis-[dioxido vanadate(V)] tetra-hydrate. AB - The asymmetric unit of the title compound, (C(6)H(9)N(2))(4)[V(4)O(12)].4H(2)O, contains half of a [V(4)O(12)](4-) anion, two 2-amino-4-methyl-pyridinium, (2a4mpH)(+), cations and two water mol-ecules. One water mol-ecule is disordered over two sets of sites with equal occupancies and the H atoms for this mol-ecule were not included in the refinement. The cation lies on an inversion center with four tetra-hedral VO(4) units each sharing two vertices, forming an eight membered ring. In the crystal, the components are linked by inter-molecular N-H?O hydrogen bonds, forming a one-dimensional network along [100]. Further stabilization is provided by weak inter-molecular C-H?O hydrogen bonds. In addition, pi-pi stacking inter-actions with centroid-centroid distances of 3.5420 (18), 3.7577 (18) and 3.6311 (19) A are observed. PMID- 22090867 TI - Hexachloridobis-{MU-2-(piperazin-1-yl)-N-[1-(2-pyrid-yl)ethyl-idene]ethanamine} trizinc dihydrate. AB - In the trinuclear title compound, [Zn(3)Cl(6)(C(13)H(20)N(4))(2)].2H(2)O, each terminal Zn(II) atom is coordinated by an N(3) donor set from the Schiff base ligands and two Cl atoms in a distorted square-pyramidal geometry. The central Zn(II) atom is tetra-hedrally coordinated by two piperazine N atoms from two Schiff base ligands and two Cl atoms. The piperazine rings adopt chair conformations. In the crystal structure, adjacent complex mol-ecules are linked into a three-dimensional network via N-H?O, C-H?Cl and C-H?O hydrogen bonds. The structure includes two water mol-ecules, one of which is disordered over two positions with occupancies of 0.753 (15) and 0.247 (15). PMID- 22090868 TI - Triethyl-ammonium hexa-MU(2)-acetato-kappaO:O'-diacetato-kappaO-aqua-MU(3)-oxido triferrate(III) toluene monosolvate. AB - The title compound, (C(6)H(16)N)[Fe(3)(CH(3)CO(2))(8)O(H(2)O)].C(7)H(8), was serendipitously crystallized from a reaction of disilanol with iron(II) acetate. The trinuclear acetatoferrate(III) anion has a triethyl-ammonium cation as the counterion. The three Fe atoms lie on the vertices of a regular triangle and are octa-hedrally coordinated. The complete coordination of the anion includes shared ligands among the three metal ions: a central tribridging O atom and six bidentate bridging acetyl groups. The six-coordinations of two of the metal ions are completed by a monodentate acetate ligand, whereas that of the third metal ion is completed by a water mol-ecule. The uncoordinated triethyl-ammonium cation is involved in N-H?O hydrogen bonding to a singly coordinated acetyl group. The coordinated aqua mol-ecule is involved in bifurcated O-H?O hydrogen bonding. C H?O inter-actions are also observed. The toluene solvent molecule is disordered over two sets of sites in a 0.609 (11):0.391 (11) ratio. PMID- 22090869 TI - Triaqua-1kappaO-MU-cyanido-1:2kappaN:C-penta-cyanido-2kappaC-tetra-kis-(dimethyl formamide-1kappaO)-1-holmium(III)-2-iron(III) monohydrate. AB - In the bimetallic cyanide-bridged title complex, [Fe(0.98)HoRu(0.02)(CN)(6)(C(3)H(7)NO)(4)(H(2)O)(3)].H(2)O, the Ho(III) ion is in a slightly distorted square-anti-prismatic arrangement formed by seven O atoms from four dimethyl-formamide (DMF) mol-ecules and three water mol-ecules, and one N atom from a bridging cyanide group connected with the Fe(III) atom which is octa-hedrally coordinated by six cyanide groups. In the crystal, mol-ecules are held together through O-H?N and O-H?O hydrogen-bonding inter-actions to form a three-dimensional framework. Elemental analysis of one of the precursors and the crystal shows that there is a slight contamination of Fe by Ru. The Fe site displays, therefore, small substitutional disorder with site-occupancy factors Fe/Ru = 0.98:0.02. The two methyl groups of two dimethyl-formamide ligands are positionally disordered with site-occupancy factors of 0.44 (3):0.56 (3) and 0.44 (3):0.56 (3). PMID- 22090870 TI - Bis(acetonitrile-kappaN)dichlorido(eta-cyclo-octa-1,5-diene)ruthenium(II) acetonitrile monosolvate. AB - In the title Ru(II) complex, [RuCl(2)(C(8)H(12))(C(2)H(3)N)(2)].CH(3)CN, the metal ion is coordinated to the centers of each of the double bonds of the cyclo octa-diene ligand, to two chloride ions (in cis positions) and to two N-atom donors (from MeCN mol-ecules) that complete the coordination sphere for the neutral complex. The coordination about the Ru(II) atom can thus be considered to be octa-hedral with a slightly trigonal distortion. There is also one acetonitrile solvent mol-ecule per mol-ecule which is outside the coordination sphere of the ruthenium atom. PMID- 22090871 TI - [Bis(pyridin-2-ylmeth-yl) ether]trichlorido-rhodium(III) dichloro-methane monosolvate: unusual hydrolysis of the methyl-ene bridge in (pyrazolylmeth yl)pyridine. AB - In the title compound, [RhCl(3)(C(12)H(12)N(2)O)].CH(2)Cl(2), the Rh(III) atom shows a slightly distorted octa-hedral geometry being coordinated by two N atoms and one O atom from the 2,2'-(oxydimethanedi-yl)dipyridine ligand and three Cl atoms. Two Cl atoms adopt a trans arrangement to the two pyridyl N atoms, while the third Cl atom and the O atoms occupy the axial site. The Rh-Cl bonds that are trans to the pyridyl N atoms are slightly longer than the Rh-Cl bond distance trans to the O atom. PMID- 22090872 TI - Tetra-MU(2)-acetato-diaqua-bis-(MU(2)-2-{[1,3-dihy-droxy-2-(oxidometh-yl)propan-2 yl]imino-meth-yl}phenolato)trimanganese(II,III) acetonitrile disolvate dihydrate. AB - In the title complex, [Mn(II)Mn(III) (2)(C(11)H(13)NO(4))(2)(CH(3)CO(2))(4)(H(2)O)(2)].2CH(3)CN.2H(2)O, there are two Mn(III) and one Mn(II) atoms. The Mn(II) atom lies on an inversion center and the Mn(III)-Mn(II)-Mn(III) angle is therefore 180 degrees , as required by crystallographic symmetry. The Mn(III) and Mn(II) atoms are six-coordinated in a distorted octa-hedral geometry. In the crystal, complex mol-ecules and solvent mol-ecules are linked into a three-dimensional network by O-H?O and O-H?N hydrogen-bonding inter-actions. PMID- 22090873 TI - Poly[[MU-1,4-bis-(4,5-dihydro-1,3-oxazol-2-yl)benzene-kappaN:N']di-MU-bromido cadmium]. AB - In the title coordination polymer, [CdBr(2)(C(12)H(12)N(2)O(2))](n), the Cd(II) ion, situated on an inversion centre, is coordinated by four bridging Br atoms and two N atoms from two 1,4-bis-(4,5-dihydro-1,3-oxazol-2-yl)benzene (L) ligands in a distorted octa-hedral geometry. The L ligand, which also lies across an inversion centre, bridges two Cd(II) ions, forming layers parallel to (010). PMID- 22090874 TI - Bis(MU-3,5-dimethyl-4H-1,2,4-triazol-4-amine-kappaN:N)bis-[bis-(thio-cyanato kappaN)zinc]-bis-(3,5-dimethyl-4H-1,2,4-triazol-4-amine-kappaN)bis-(thio-cyanato kappaN)zinc (1/2). AB - In the crystal structure of the title 1:2 adduct, [Zn(2)(NCS)(4)(C(4)H(8)N(4))(2)].2[Zn(NCS)(2)(C(4)H(8)N(4))(2)] or (Ia).2(Ib), each Zn(II) atom is coordinated in a distorted tetra-hedral geometry by four N atoms from two triazole rings of two 4-amino-3,5-dimethyl-1,2,4-triazole (admt) ligands and two NCS(-) ligands. In (Ia), double N(1):N(2)-bridging admt ligands connect two Zn(II) atoms, forming a dimer with a Zn(2)(admt)(2) six-membered metallacycle located on a crystallographic inversion center. In (Ib), the admt ligands exhibit monodentate N(1)-coordination modes. Weak N-H?N, N-H?S and C-H?S hydrogen bonds play an important role in the inter-molecular packing. The S and C atoms of two thiocyanato ligands are disordered over two sets of sites in ratios of 0.57 (3):0.43 (3) and 0.63 (3):0.37 (3), respectively. PMID- 22090875 TI - catena-Poly[[diaqua-calcium]bis-[MU-2-(1,3-dioxoisoindolin-2-yl)acetato] kappaO,O':O;kappaO:O,O']. AB - In the title complex, [Ca(C(10)H(6)NO(4))(2)(H(2)O)(2)](n), the Ca(II) atom lies on a twofold rotation axis and adopts a dodeca-hedral geometry. The Ca(II) atom is octa-coordinated by two O atoms from two water mol-ecules and six O atoms from four acetate ligands. Each acetate acts as a tridentate ligand bridging two Ca(II) atoms, resulting in a chain running along the c axis. O-H?O and C-H?O hydrogen bonds connect the chains into a two-dimensional network parallel to [011]. pi-pi inter-actions between adjacent isoindoline-1,3-dione rings [centroid centroid distance = 3.4096 (11) A] further consolidate the structure. One of the carboxylate O atoms is disordered over two sites in a 0.879 (12):0.121 (12) ratio. PMID- 22090876 TI - MU-Oxido-bis-{bis-[(penta-fluoro-phen-yl)methano-lato](eta-penta-methyl-cyclo penta-dien-yl)titanium(IV)}. AB - The dinuclear title complex, [Ti(2)(C(10)H(15))(2)(C(7)H(2)F(5)O)(4)O], features two Ti(IV) atoms bridged by an O atom. Each Ti atom is bonded to a eta(5)-penta methyl-cyclo-penta-dienyl ring, two (penta-fluoro-phen-yl)methano-late anions and to the bridging O atom. The environment around each Ti atom can be considered as a distorted tetra-hedron. PMID- 22090877 TI - 3,5-Diamino-4H-1,2,4-triazol-1-ium hydroxonium bis-(pyridine-2,6-di-carboxyl ato)cobaltate(II) pyridine-2,6-dicarb-oxy-lic acid monohydrate. AB - The asymmetric unit of the title complex, (C(2)H(6)N(5))(H(3)O)[Co(C(7)H(3)NO(4))(2)].C(7)H(5)NO(4).H(2)O, contains a Co(II) ion coordin-ated by four O atoms and two N atoms from two dipicolinate ligands in a disorted octa-hedral environment, a protonated triazole mol-ecule, a neutral pyridine-2,6-dicarb-oxy-lic acid mol-ecule, a hydroxonium ion and a solvent water mol-ecule. In the crystal, the components are linked into a three dimensional framework by inter-molecular O-H?O, N-H?O and N-H?N and weak C-H?O hydrogen bonds. In addition, pi-pi stacking inter-actions with centroid-centroid distances in the range 3.4809 (7)-3.8145 (6) A are observed. PMID- 22090878 TI - Poly[aqua-[MU(5)-5-(isonicotinamido)-isophthalato][MU(4)-5-(isonicotinamido) isophthalato]cerium(III)silver(I)]. AB - The 4d-4f heteronuclear title complex, [AgCe(C(14)H(8)N(2)O(5))(2)(H(2)O)](n), has a three-dimensional framework structure, generated by the carboxyl-ate and pyridyl groups of the 5-(isonicotinamido)-isophthalate (INAIP) ligands bridging the metal ions. The Ce(III) atom is coordinated by eight O atoms from six INAIP ligands and a water mol-ecule in a distorted tricapped trigonal-prismatic geometry, while the Ag(I) atom has a distorted trigonal-planar AgN(2)O geometry. O-H?O and N-H?O hydrogen bonds and pi-pi inter-actions between the pyridine and benzene rings [centroid-centroid distances = 3.642 (4) and 3.624 (3) A] stabilize the crystal structure. PMID- 22090879 TI - Redetermination of diaqua-tetra-kis-(dimethyl-formamide-kappaO)magnesium dichloride. AB - The crystal structure of the title compound, [Mg(C(3)H(7)NO)(4)(H(2)O)(2)]Cl(2), in which the Mg ion lies on a crystallographic inversion centre, confirms that of the previous room-temperature study [Pavanello et al. (1995 ?). Main Group Met. Chem.18, 9-19]. This redetermination at 113 K has improved geometry precision by almost an order of magnitude [e.g. Mg-O(w) (w = water) distances = 2.094 (4) and 2.0899 (7) A in the old and new structures, respectively] and allowed the water H atoms to be located and their positions refined. In the crystal, O-H?Cl hydrogen bonds between the two aqua ligands of the complex mol-ecule and neighboring chloride counter-anions generate supra-molecular chains propagating along [010]. The dicationic [Mg(DMF)(4)(H(2)O)(2)] unit (DMF is dimethyl-formamide) adopts a slightly distorted octa-hedral geometry in which the Mg atom is coordinated by four DMF O atoms in a pseudo-tetra-gonal arrangement and two trans aqua ligands. PMID- 22090880 TI - catena-Poly[[dibromidomercury(II)]-MU-3,6-bis-(2-pyridyl-sulfan-yl)pyridazine kappaN:N]. AB - In the title coordination polymer, [HgBr(2)(C(14)H(10)N(4)S(2))](n), the Hg(II) atom is four-coordinated in a distorted tetra-hedral geometry by the two N atoms of the pyridyl groups of different 3,6-bis-(2-pyridyl-sulfan-yl)pyridazine ligands and two Br atoms. The bridging function of the cis ligands leads to a helical chain structure along [100]. PMID- 22090881 TI - Poly[[bis-(nitrato-kappaO)bis-(MU(4)-pyridine-4-carboxyl-ato)tetra-kis-(MU(3) pyridine-4-carboxyl-ato)octa-silver(I)] hemihydrate]. AB - In the title coordination polymer, {[Ag(8)(C(6)H(4)NO(2))(6)(NO(3))(2)].0.5H(2)O}(n), two Ag(I) ions are two coordinate within an AgN(2) set and six are three-coordinate within AgN(2)O and AgO(3) sets. The Ag-N and Ag-O distances are in the ranges 2.150 (5)-2.198 (5) and 2.142 (4)-2.702 (5) A, respectively. A two-dimensional coordination network is formed parallel to (100). The O atom of the disordered solvent water mol-ecule is located on an inversion center. PMID- 22090882 TI - N-(Quinolin-8-yl)ferrocene-1-carbox-amide. AB - In the title compound, [Fe(C(5)H(5))(C(15)H(11)N(2)O)], the cyclo-penta-dienyl rings are essentially eclipsed, and the dihedral angle between the cyclo-penta dienyl ring planes is 0.632 (10) degrees . The Fe atom is slightly closer to the substituted cyclo-penta-dienyl ring, with an Fe-centroid distance of 1.6374 (3) A [1.6494 (3) A for the unsubstituted ring]. The amide group is essentially coplanar with the substituted cyclo-penta-dienyl ring, with an N-C(O)-C-C torsion angle of 2.3 (3) degrees . PMID- 22090883 TI - Bis(MU(2)-2-amino-5-nitro-benzoato)bis-(2-amino-5-nitro-benzoato)octa-butyldi MU(3)-oxido-tetra-tin(IV). AB - In the title complex, [Sn(4)(C(4)H(9))(8)(C(7)H(5)N(2)O(4))(4)O(2)], all four Sn(IV) atoms are five-coordinated with distorted trigonal-bipyramidal SnC(2)O(3) geometries. Two Sn(IV) atoms are coordin-ated by two butyl groups, one benzoate O atom and two bridging O atoms, whereas the other two Sn(IV) atoms are coordinated by two butyl groups, two benzoate O atoms and a bridging O atom. All the butyl groups are equatorial with respect to the SnO(3) trigonal plane. In the crystal, mol-ecules are linked into a two-dimensional layer parallel to the ab plane by inter-molecular N-H?O and C-H?O hydrogen bonds and further stabilized by a pi-pi inter-action [centroid-centroid distance = 3.6489 (11) A]. Intra-molecular N-H?O and C-H?O hydrogen bonds stabilize the mol-ecular structure. Two of the butyl groups are each disordered over two sets of sites with site-occupancy ratios of 0.510 (4):0.490 (4) and 0.860 (5):0.140 (5). PMID- 22090884 TI - Bis[1-benzyl-3-(4-methyl-phen-yl)imidazol-2-yl-idene]silver(I) hexa-fluorido phosphate. AB - The title silver N-heterocyclic carbene compound, [Ag(C(17)H(16)N(2))(2)]PF(6), crystallizes as a mononuclear salt. The two imidazole rings, which are almost coplanar [maximum deviation from the least squares plane of 0.05 (2) A], are linked by the Ag atom with a C-Ag-C angle of 178.60 (9) degrees . In the crystal, C-H?F hydrogen bonds, weak pi-pi inter-actions [centroid-centroid distances = 3.921 (1) and 3.813 (3) A] and C-H?pi inter-actions lead to a supermolecular structure. PMID- 22090885 TI - 3,3'-Dimethyl-1,1'-(propane-1,3-di-yl)diimidazol-1-ium bis-(1,2-dicyano-ethene 1,2-dithiol-ato-kappaS,S')nickelate(II). AB - In the title compound, (C(11)H(18)N(4))[Ni(C(4)N(2)S(2))(2)], the asymmetric contains one half-complex, with the cation placed on a twofold axis and the anion located on an inversion center. The Ni(II) ion in the anion is coordinated by four S atoms of two maleonitrile-dithiol-ate ligands, and exhibits the expected square-planar coordination geometry. PMID- 22090886 TI - Poly[[aqua-(MU(7)-biphenyl-3,3',4,4'-tetra-carboxyl-ato)(1,10 phenanthroline)dicobalt(II)] monohydrate]. AB - In the title compound, {[Co(2)(C(16)H(6)O(8))(C(12)H(8)N(2))(H(2)O)(2)].H(2)O}(n), one Co(II) ion has a {CoN(2)O(4)} distorted octa-hedral environment defined by two N atoms of one 1,10 phenanthroline (phen) ligand, three O atoms of the carboxyl-ate groups of three biphenyl-3,3',4,4'-tetra-carboxyl-ate (BPTC) ligands, one of which is bidentate, and one O atom from one coordinated water mol-ecule. The other Co(II) atom is surrounded by six O atoms from four different BPTC ligands and one coordinated water mol-ecule. Each BPTC ligand forms eight coordination bonds with seven Co(II) atoms, leading to a layer structure along the ac plane. Uncoordinated water mol-ecules occupy the space between the layers, and inter-act via inter layer O-H?O hydrogen bonds along the b axis, generating a three-dimensional supra molecular network. PMID- 22090887 TI - Triaqua-(7-oxabicyclo-[2.2.1]heptane-2,3-dicarboxyl-ato-kappaO,O,O)cobalt(II) monohydrate. AB - The title complex, [Co(C(8)H(8)O(5))(H(2)O)(3)].H(2)O, was synthesized by reaction of cobalt acetate with 7-oxabicyclo-[2.2.1]heptane-2,3-dicarb-oxy-lic anhydride (norcantharidin) in aqueous solution. In the mol-ecule, the Co(II) atom is six-coordinated in a distorted octa-hedral environment, binding to the bridging O atom of the bicyclo-heptane unit, to two O atoms from monodentate carboxyl-ate groups and to three water O atoms. The crystal structure is stabilized by several O-H?O hydrogen-bonding inter-actions involving both the coordinated and uncoordinated water mol-ecules as donors and the carboxyl-ate O atoms of neighbouring mol-ecules as acceptors. PMID- 22090888 TI - Poly[[tetra-aqua-bis-(MU(3)-1H-imidazole-4,5-dicarboxyl-ato)tetra-kis-(MU(2)-1H imidazole-4,5-dicarboxyl-ato)tricobalt(II)diytterbium(III)] dihydrate]. AB - The asymmetric unit of the title compound, {[Co(3)Yb(2)(C(5)H(2)N(2)O(4))(6)(H(2)O)(4)].2H(2)O}(n), contains one Yb(III) ion, two Co(II) ions (one situated on an inversion centre), three imidazole-4,5 dicarboxyl-ate ligands, two coordinated water mol-ecules and one uncoordinated water mol-ecule. The Yb(III) ion is seven-coordinated, in a monocapped trigonal prismatic coordination geometry, by six O atoms from three imidazole-4,5 dicarboxyl-ate ligands and one water O atom. Both Co(II) ions are six-coordinated in a slightly distorted octa-hedral geometry. The Co(II) ion that is located on an inversion center is coordinated by two O atoms from two water mol-ecules, as well as two O atoms and two N atoms from two imidazole-4,5-dicarboxyl-ate ligands. The second Co(II) ion is bonded to four O atoms and two N atoms from four imidazole-4,5-dicarboxyl-ate ligands. These metal coordination units are connected by bridging imidazole-4,5-dicarboxyl-ate ligands, generating a three dimensional network. The crystal structure is further stabilized by N-H?O, O-H?O and C-H?O hydrogen-bonding inter-actions involving the water mol-ecules and the imidazole-4,5-dicarboxyl-ate ligands. PMID- 22090889 TI - Bis(1H-imidazole-kappaN)bis-(2-methyl-benzoato-kappaO)bis-(2-methyl-benzoic acid kappaO)copper(II). AB - The structure of the title compound, [Cu(C(8)H(7)O(2))(2)(C(3)H(4)N(2))(2)(C(8)H(8)O(2))(2)], consists of centrosymmetric monomeric units, in which the Cu(II) atom has a tetra-gonally distorted octa-hedral coordination involving two imidazole N atoms and two carboxyl-ate O atoms in the square plane [Cu-N = 1.964 (3) and Cu-O = 1.960 (2) A] and 2-methyl-benzoic acid O atoms in axial sites [Cu-O = 2.753 (3) A]. Within the complex, the carb-oxy-lic acid forms intra-molecular O-H?O hydrogen bonds, while the mol-ecules are assembled through N-H?O(carbox-yl) hydrogen bonds into chains extending along the a-axis direction. These chains are further linked by weak pi-pi inter-actions [centroid-centroid separation = 3.930 (2) A]. PMID- 22090890 TI - Bis(acetonitrile-kappaN)diaqua-bis-(perchlorato-kappaO)copper(II). AB - In the title compound, [Cu(ClO(4))(2)(CH(3)CN)(2)(H(2)O)(2)], the Cu(2+) ion, located on a special position (site symmetry [Formula: see text]), is coordinated by six monodentate ligands, viz. an N-coordin-ated acetonitrile, a perchlorate anion and a water mol-ecule, and their symmetry-related counterparts. The perchlorate anion is disordered over two sets of sites with occupancies of 0.53 (2) and 0.47 (2). The crystal structure is stabilized by O-H?O hydrogen bonds involving the perchlorate ion and aqua H atoms. PMID- 22090891 TI - {MU-6,6'-Dimeth-oxy-2,2'-[ethane-1,2-diyl-bis(nitrilo-methanylyl idene)]diphenolato-1kappaO,O,O,O;2kappaO,N,N',O}(methanol-1kappaO)(tetra fluoridoborato-1kappaF,F')-2-copper(II)-1-sodium. AB - In the dinuclear salen-type title complex, [CuNa(BF(4))(C(18)H(18)N(2)O(4))(CH(3)OH)], the Cu(II) atom is chelated by two O atoms and two N atoms of the deprotonated Schiff base in a square-planar geometry. The Na atom is seven-coordinate as it is linked to four O atoms of the same Schiff base ligand, one O atom of the methanol and two tetra-fluorido-borate F atoms. The remaining two F atoms of the anion are disordered over two sites in a 0.598 (18):0.402 (18) ratio. PMID- 22090892 TI - Di-MU-nicotinamide-kappaN:O;kappaO:N-bis-[aqua-bis-(4-bromo-benzoato) kappaO;kappaO,O'-manganese(II)]. AB - In the centrosymmetric dinuclear title compound, [Mn(2)(C(7)H(4)BrO(2))(4)(C(6)H(6)N(2)O)(2)(H(2)O)(2)], the Mn(II) atom is coordinated by one N atom from one bridging nicotinamide ligand and one O atom from another symmetry-related bridging nicotinamide ligand, three O atoms from two 4-bromo-benzoate ligands and one water mol-ecule in a distorted octa-hedral geometry. The dihedral angles between the carboxyl-ate groups and the adjacent benzene rings are 10.89 (16) and 8.4 (2) degrees , while the benzene rings are oriented at a dihedral angle of 6.09 (13) degrees . Inter-molecular O-H?O, N-H?O and weak C-H?O hydrogen bonds link the mol-ecules into a three-dimensional network. pi-pi inter-actions, indicated by short centroid-centroid distances [3.845 (2) A between the benzene rings, 3.650 (2) A between the pyridine rings and 3.700 (3) A between the benzene and pyridine rings] further stabilize the structure. PMID- 22090893 TI - Poly[[MU-aqua-tetraaquabis(MU-2-hydroxy-4-oxocyclobut-1-ene-1,3 diolato)strontium] hemihydrate]. AB - In the title coordination polymer, {[Sr(C(4)HO(4))(2)(H(2)O)(5)].0.5H(2)O}(n), the Sr(2+) ion is coordinated by three monodentate hydrogensquarate (hsq) anions and six aqua ligands in a distorted SrO(9) monocapped square-anti-prismatic geometry. The hsq anions and water mol-ecules bridge the metal ions into infinite sheets lying parallel to (100). The O atom of the uncoordinated water mol-ecule lies on a crystallographic twofold axis. The packing is stabilized by numerous O H?O hydrogen bonds. PMID- 22090894 TI - {N'-[(E)-1-(5-Bromo-2-oxidophen-yl)ethyl-idene-kappaO]-4-methyl-benzohydrazidato kappaN',O}(pyridine-kappaN)nickel(II). AB - The central Ni(II) atom in the title complex, [Ni(C(16)H(13)BrN(2)O(2))(C(5)H(5)N)], is in a square-planar trans-N(2)O(2) environment defined by the NO(2) donor atoms of the tridentate hydrazone ligand and the monodentate pyridine ligand. The pyridine mol-ecule forms a dihedral angle of 9.99 (11) degrees with the least-squares plane through the NiN(2)O(2) atoms. PMID- 22090895 TI - catena-Poly[[(aqualithium)-MU-3-carboxypyrazine-2-carboxylato-kappaO,N:O,N] monohydrate]. AB - The polymeric structure of the title compound {[Li(C(6)H(3)N(2)O(4))(H(2)O)].H(2)O}(n), contains two symmetry-independent Li(I) complex units, both having distorted trigonal-bipyramidal coordination environments. The Li(I) ions are bridged by both the N and O atoms of the ligands, generating two symmetry-independent polymeric chains propagating along the b-axis direction. In both ligands, the second carboxyl-ato O atom remains protonated, serving as a donor in a short intra-molecular O-H?O hydrogen bond. The coordination of each Li(I) ion is completed by a water O atom. The ribbons are held together by a network of O-H?O hydrogen bonds in which the coordinated and uncoordinated water mol-ecules are donors and the carboxyl-ato O atoms act as acceptors. PMID- 22090896 TI - (Acetonitrile-kappaN)[2-(diphenylphosphan-yl)ethanamine-kappaN,P][(1,2,3,4,5-eta) 1,2,3,4,5-pentamethylcyclopentadienyl]iron(II) hexafluoridophosphate tetrahydrofuran monosolvate. AB - In the title cationic Cp(*)Fe(II) complex, [Fe(C(10)H(15))(CH(3)CN)(C(14)H(16)NP)]PF(6).C(4)H(8)O, the metal ion is coordinated by the eta(5)-Cp* ring as well as the P and N atoms of the chelating 2-(diphenyl-phosphino)ethyl-amine ligand and an additional acetonitrile mol-ecule in a piano-chair conformation. The PF(6) (-) anion is disordered over two sets of sites with occupancies of 0.779 (7) and 0.221 (7). PMID- 22090897 TI - catena-Poly[[(3-methyl-pyridine)-copper(I)]-MU-cyanido-copper(I)-MU-cyanido]. AB - In the title complex, [Cu(2)(CN)(2)(C(6)H(7)N)](n), there are two copper atoms with different coordination environments. One Cu atom (Cu1) is linked to the two cyanide ligands, one N atom from a pyridine ring while the other (Cu2) is coordinated by the two cyanide ligands in a slightly distorted tetra-hedral geometry and linked to Cu1, forming a triangular coordination environment. The Cu atoms are bridged by bidentate cyanide ligands, forming an infinite Cu-CN chain. One cyanide ligand is equally disordered over two sets of sites, exchanging C and N atoms coordinated to both metal atoms. However, one cyanide group is not disordered and it coordinates to Cu1 via the N atom whereas its C-atom counterpart coordinates Cu2. The 3-methyl-pyridine (3MP) ligand coordinates through the N atom to Cu1 as a terminal ligand, which originates from decyanation of 3-pyridyl-acetonitrile under hydro-thermal conditions. Adjacent Cu-CN chains are inter-connected through Cu?Cu inter-actions [2.8364 (10) A], forming a three dimensional framework. PMID- 22090898 TI - catena-Poly[[(nitrito-kappaO,O')silver(I)]-MU-1,2-bis-[1-(pyridin-4-yl)ethyl idene]hydrazine-kappaN:N']. AB - The asymmetric unit of the title compound, [Ag(NO(2))(C(14)H(14)N(4))](n), contains half of the repeating formula unit (Z' = 1/2). The Ag(I) ion lies on a twofold rotation axis. The primary structure consists of a one-dimensional coordination polymer formed by the Ag(I) ions and the bipyridyl azine ligand in which there is an inversion center at the mid-point of the N-N bond. The nitrite anion inter-acts with the Ag(I) ion through a chelating MU(2) inter-action involving both O atoms. In the crystal, the coordination chains are parallel and inter-act through Ag?pi [3.220 (2) A] and pi-pi [3.489 (3) A] inter-actions. PMID- 22090899 TI - catena-Poly[tris(2,4,6-trimethyl-anilinium) [(tetrachloridocadmium)-MU chlorido]]. AB - The asymmetric unit of the title compound, {(C(9)H(14)N)(3)[CdCl(5)]}(n), comprises three 2,4,6-trimethyl-aniline dications and one half of the [Cd(2)Cl(10)](6-) anion. The Cd atoms are each coordinated by six Cl atoms, with octa-hedra linked by bridging, apical Cl atoms, forming linear chains running parallel to the a axis. The trimethylanilinium cations form stacks between the chains of CdCl(6) octa-hedra. PMID- 22090900 TI - trans-Bis(acetato-kappaO)diaquabis-(2-amino-pyrazine-kappaN)manganese(II) dihydrate. AB - The Mn(II) atom in the title compound, [Mn(CH(3)COO)(2)(C(4)H(5)N(3))(2)(H(2)O)(2)].2H(2)O, is situated on a center of inversion and shows an octa-hedral coordination polyhedron made up by four O atoms and two N atoms. The octa-hedron is somewhat tetra-gonally distorted owing to the longer Mn-N bond [2.323 (3) A]. The mononuclear complex mol-ecule and uncoordinated water mol-ecules are linked by O-H?N, N-H?O and O-H?O hydrogen bonds, generating a three-dimensional network. PMID- 22090901 TI - Bis[MU(2)-bis-(diphenyl-phosphan-yl)methane-kappaP:P']bis-(MU(4)-diphenyl phosphinato-kappaO:O:O':O')bis-[MU(2)-trifluoro-methane-sulfonato-(0.546/0.454)] kappaO:O';kappaO:O-tetra-silver(I) acetonitrile disolvate. AB - In the centrosymmetric tetra-nuclear title compound, [Ag(4)(C(12)H(10)O(2)P)(2)(CF(3)O(3)S)(2)(C(25)H(22)P(2))(2)].2CH(3)CN, the Ag(I) atom is coordinated by one P atom from a bis-(diphenyl-phosphan-yl)methane (dppm) ligand, two O atoms from two diphenyl-phosphinate (dpp) ligands and one O atom from a trifluoro-methane-sulfonate (OTf) anion in a highly distorted tetra-hedral geometry. Four Ag(I) atoms are bridged by two dppm ligands, two dpp ligands and two OTf anions, forming a tetra-nuclear complex. An weak intra-molecular Ag?Ag [3.2692 (14) A] inter-action is observed. The OTf anion and one of the phenyl groups in the dppm ligand are disordered over two sets of positions in a 0.546 (4):0.454 (4) ratio. The 0.546-occupied OTf is bonded to two Ag atoms in a MU (kappa(2)O:O') mode, while the 0.454-occupied OTf is bonded in a MU-(kappa(2)O:O) mode. The methyl group of the acetonitrile solvent mol-ecule is also disordered over two positions with equal occupancy factors. PMID- 22090902 TI - Bis[1-(4-chloro-benz-yl)pyridinium] bis-(1,2,5-thia-diazole-3,4-dithiol ato)nickelate(II). AB - The asymmetric unit of the salt, (C(12)H(11)ClN)(2)[Ni(C(2)N(2)S(3))(2)], comprises one cation and a half of Ni(tdas)(2) (tdas = 1,2,5-thia-diazole-3,4 dithiol-ate) anion. The Ni(II) atom is located at a centre of inversion. The Ni(II) atom has a square-planar coordination with Ni-S distances of 2.2052 (4) and 2.1970 (5) A. In crystal, weak C-H?S and C-H?Ni contacts are observed between the anions and cations. PMID- 22090903 TI - catena-Poly[(dichloridocadmium)-di-MU-chlorido-[bis-(morpholinium-kappaO)cadmium] di-MU-chlorido]. AB - In the title compound, [Cd(2)Cl(6)(C(4)H(10)NO)(2)](n), the coordination geometry of each Cd(II) ion is distorted octa-hedral, but with quite different coordination environments. One Cd(II) atom is coordinated by four Cl atoms and two O atoms from two morpholinium ligands, while the other is coordinated by six Cl atoms. Adjacent Cd(II) atoms are inter-connected alternately by paired chloride bridges, generating a chain parallel to the a axis. Inter-chain N-H?Cl inter-actions form a two-dimensional network. PMID- 22090904 TI - {2,2'-[(2,2-Dimethylpropane-1,3-diyl-dinitrilo)bis(phenylmethylidyne)]di phenolato}copper(II). AB - The complete mol-ecule of the title complex, [Cu(C(31)H(28)N(2)O(2))], is generated by the application of twofold symmetry; the Cu and CMe(2) atoms lie on the axis. The geometry around the Cu(II) atom is distorted square-planar. The dihedral angle between the two phenyl rings is 76.0 (3) degrees . The crystal packing is stabilized by inter-molecular C-H?pi inter-actions. PMID- 22090905 TI - {MU-N,N,N',N'-Tetra-kis[(diphenyl-phosphan-yl)meth-yl]benzene-1,4-diamine}-bis [(2,2'-bipyrid-yl)copper(I)] bis-(tetra-fluoridoborate). AB - In the title compound, [Cu(2)(C(10)H(8)N(2))(2)(C(58)H(52)N(2)P(4))](BF(4))(2), the dinuclear cation lies on an inversion centre. The Cu(I) atom is coordinated by two N atoms from a 2,2'-bipyridine ligand and two P atoms from an N,N,N',N' tetra-kis-[(diphenyl-phos-phan-yl)meth-yl]benzene-1,4-diamine ligand in a distorted tetra-hedral geometry. In the crystal, inter-molecular C-H?F hydrogen bonds link the ions into layers parallel to [[Formula: see text]01]. pi-pi inter actions [centroid-centroid distance = 3.668 (4) A] are also observed. One F atom of the anion is disordered over two orientations with a refined occupancy ratio of 0.675 (13):0.325 (13). PMID- 22090906 TI - MU-Oxido-bis-[bis-(penta-fluoro-phenolato)(eta-penta-methyl-cyclo-penta-dien yl)titanium(IV)]. AB - The dinuclear title complex, [Ti(2)(C(10)H(15))(2)(C(6)F(5)O)(4)O], features two Ti(IV) atoms bridged by an O atom, which lies on an inversion centre. The Ti(IV) atom is bonded to a eta(5)-penta-methyl-cyclo-penta-dienyl ring, two penta-fluoro phenolate anions and to the bridging O atom. The environment around the Ti(IV) atom can be considered as a distorted tetra-hedron. The cyclo-penta-dienyl ring is disordered over two sets of sites [site occupancy = 0.824 (8) for the major component]. PMID- 22090907 TI - Tetra-kis(acetonitrile-kappaN)lithium hexa-fluoridophosphate acetonitrile monosolvate. AB - In the title compound, [Li(CH(3)CN)(4)]PF(6).CH(3)CN, the asymmetric unit consists of three independent tetra-hedral [Li(CH(3)CN)(4)](+) cations, three uncoordinated PF(6) (-) anions and three uncoordinated CH(3)CN solvent mol ecules. The three anions are disordered over two sites through a rotation along one of the F-P-F axes. The relative occupancies of the two sites for the F atoms are 0.643 (16):0.357 (16), 0.677 (10):0.323 (10) and 0.723 (13):0.277 (13). The crystal used was a racemic twin, with approximately equal twin components. PMID- 22090908 TI - Bis[2-(2-fur-yl)-1-(2-furylmeth-yl)-1H-benzimidazole-kappaN]diiodidocadmium. AB - In the title complex, [CdI(2)(C(16)H(12)N(2)O(2))(2)], the Cd(II) atom is located on a twofold rotation axis and is four-coordinated by two N atoms from symmetry related 2-(2-fur-yl)-1-(2-furyl-meth-yl)-1H-benzimidazole ligands and two I atoms in a distorted tetra-hedral configuration. The benzimidazole rings in adjacent mol-ecules are parallel, with an average inter-planar distance of 3.486 A. The I atom is disordered over two sites in a 0.85 (5):0.15 (5) ratio. PMID- 22090909 TI - Tetra-ethyl-ammonium tri-MU-phenolato-bis-[tricarbonyl-manganate(I)]. AB - The title compound, (C(8)H(20)N)[Mn(2)(C(6)H(5)O)(3)(CO)(6)], was synthesized from [Mn(CO)(3)(CH(3)CN)(3)]BF(4) and (C(8)H(20)N)(OC(6)H(5)). The binuclear anion exhibits a pseudo-threefold symmetry and contains two six-coordinate Mn atoms. Each metal atom is coordinated by three facially oriented CO ligands and three doubly-bridging phenolate ligands. The average O-Mn-O bond angle is 74.9 (7) degrees in the Mn(2)O(3) metal-phenolate dimeric core, yielding a distorted octa-hedron for each metal. PMID- 22090910 TI - Poly[(MU-2-acet-oxy-benzoato)(2-acet-oxy-benzoato)-MU-aqua-mercury(II)]. AB - In the title compound, [Hg(C(9)H(7)O(4))(2)(H(2)O)](n), the Hg(II) ion is five coordinated by three acetylsalicylate anions and water leading to the formation of a coordination polymer extending parallel to (001). O-H?O and C-H?O hydrogen bonds are effective in the stabilization of the crystal structure. PMID- 22090911 TI - Bis(MU-4-amino-3,5-dimethyl-4H-1,2,4-triazole-kappaN:N)bis-(dibromidozinc). AB - The centrosymmetric dimeric title complex, [Zn(2)Br(4)(C(4)H(8)N(4))(2)], is isotypic with its [Zn(2)Cl(4)(C(4)H(8)N(4))(2)], [Zn(2)I(4)(C(4)H(8)N(4))(2)] and [Co(2)Cl(4)(C(4)H(8)N(4))(2)] analogues. The zinc atom is bonded to two N atoms belonging to triazole bridging rings and to two terminal bromide ligands, in a geometry close to tetra-hedral. Weak N-H?Br hydrogen bonds, with the amine functions as donor groups, are observed in the crystal structure, forming a three dimensional supra-molecular network. PMID- 22090912 TI - trans-Dichloridobis(3,5-dimethyl-pyridine-kappaN)(ethano-lato-kappaO)oxido rhenium(V). AB - The title compound, [Re(C(2)H(5)O)Cl(2)O(C(7)H(9)N)(2)], was crystallized from ethanol. The crystal structure of this complex contains a Re(V) atom in a slightly distorted octahedral coordination geometry with pairs of equivalent ligands in trans positions. Adjacent complex mol-ecules are linked by weak C-H?Cl hydrogen bonds. The crystal structure is additionally stabilized by pi-pi stacking inter-actions between the aromatic rings with centroid-centroid distances of 3.546 (4) A. PMID- 22090913 TI - Poly[bis-[MU-1,4-bis-(imidazol-1-ylmeth-yl)benzene]-dichloridomanganese(II)]. AB - In the crystal structure of the title compound, [MnCl(2)(C(14)H(14)N(4))(2)](n), the Mn(II) atom, lying on an inversion center, is coordinated by four N atoms from four 1,4-bis-(imidazol-1-ylmeth-yl)benzene (bimb) ligands and two Cl(-) anions in a distorted octa-hedral geometry. The bimb ligands bridge the Mn(II) atoms, forming a two-dimensional polymeric complex, which is composed of a 52 membered [Mn(4)(bimb)(4)] ring with distances of 7.7812 (2) and 27.4731 (9) A between opposite metal atoms. Weak C-H?pi inter-actions are present in the crystal structure. PMID- 22090915 TI - Bis(MU(2)-2-chloro-benzoato-kappaO:O')bis-[(2-chloro-benzoato-kappaO)(1,10 phenanthroline-kappaN:N')copper(II)] dihydrate. AB - In the title compound, [Cu(2)(C(7)H(4)ClO(2))(4)(C(12)H(8)N(2))(2)].2H(2)O, the two crystallographically independent dinuclear complex mol-ecules, A and B, have different Cu?Cu separations, viz. 3.286 (1) A in A and 3.451 (1) A in B. Both independent mol-ecules reside on inversion centres, so the asymmetric unit contains a half-mol-ecule each of A and B and two water mol-ecules. Each Cu atom has a square-pyramidal environment, being coordinated by two O atoms from two bridging 2-chloro-benzoate ligands, one O atom from a monodentate 2-chloro benzoate ligand and two N atoms from a 1,10-phenanthroline ligand. The water mol ecules can also be considered as coordinating ligands, which complete the coordination geometry up to distorted octa-hedral with elongated Cu-O distances, viz. 3.024 (3) A in A and 2.917 (3) A in B. In the crystal, weak inter-molecular C-H?O inter-actions contribute to the consolidation of the crystal packing. PMID- 22090914 TI - catena-Poly[[(1,10-phenanthroline)zinc]-MU-2,2'-oxydibenzoato]. AB - In the title one-dimensional coordination polymer, [Zn(C(14)H(8)O(5))(C(12)H(8)N(2))](n), the Zn(II) ion is in a distorted octa hedral coordination geometry with four O atoms from two carboxyl-ate groups in bidentate chelating modes and two N atoms from a 1,10-phenanthroline ligand. The two terminal carboxyl-ate groups bind the Zn(II) ions, leading to a chain along the c axis. Adjacent chains are further linked by inter-molecular pi-pi inter actions with a shortest centroid-centroid distance of 3.586 (3) A, forming a two dimensional supra-molecular architecture with (6,3)-network topology. PMID- 22090916 TI - Tetra-kis(MU-4-tert-butyl-benzoato)-kappaO:O,O';kappaO,O':O';kappaO:O'-bis-[aqua bis-(4-tert-butyl-benzoato-kappaO,O')(4-tert-butyl-benzoic acid kappaO)praseodymium(III)]. AB - The reaction of praseodymium nitrate and 4-tert-butyl-benzoic acid (tBBAH) in aqueous solution yielded the dinuclear title complex, [Pr(2)(C(11)H(13)O(2))(6)(C(11)H(14)O(2))(2)(H(2)O)(2)], which has non crystallographic C(i) symmetry. The two Pr(III) ions are linked by two bridging and two bridging-chelating tBBA ligands, with a Pr?Pr separation of 4.0817 (9) A. Each Pr(III) ion is nine-coordinated by one chelating tBBA ion, one monodentate tBBAH ligand and one water mol-ecule in a distorted tricapped trigonal-prismatic environment. The complex mol-ecules are linked into infinite chains along the c axis by inter-molecular O-H?O hydrogen bonds. PMID- 22090917 TI - Aqua-(cyanido-kappaC){6,6'-dimeth-oxy-2,2'-[o-phenyl-enebis(nitrilo-methanylyl idene)]diphenolato-kappaO,N,N',O}cobalt(III) acetonitrile monosolvate. AB - In the title complex, [Co(C(22)H(18)N(2)O(4))(CN)(H(2)O)].CH(3)CN, the Co(III) ion is six-coordinated in a distorted octa-hedral environment defined by two N atoms and two O atoms from a salen ligand in the equatorial plane and one O atom from a water mol-ecule and one C atom from a cyanide group at the axial positions. O-H?O hydrogen bonds connect adjacent complex mol-ecules into dimers. C-H?N hydrogen bonds and pi-pi inter-actions between the benzene rings [centroid centroid distances = 3.700 (2) and 3.845 (2) A] are also present. PMID- 22090918 TI - {MU-1,2-Bis[bis(4-meth-oxy-phen-yl)phosphan-yl]-1,2-dimethyl-hydrazine kappaP:P'}bis-[chloridogold(I)] tetra-hydro-furan disolvate. AB - The title compound, [Au(2)Cl(2)(C(30)H(34)N(2)O(4)P(2))].2C(4)H(8)O, is formed from a bidentate phosphine ligand complexed to two almost linearly coordinated gold(I) atoms [P-Au-Cl = 175.68 (3) A]. The nuclei are 3.122 (2) A apart. The mol ecule exhibits a twofold rotation axis. PMID- 22090919 TI - Diaqua-bis-(N,N'-diethyl-nicotinamide-kappaN)bis-(4-fluoro-benzoato kappaO)copper(II). AB - The asymmetric unit of the title mononuclear Cu(II) complex, [Cu(C(7)H(4)FO(2))(2)(C(10)H(14)N(2)O)(2)(H(2)O)(2)], contains one-half of the mol-ecule. The Cu(II) ion is located on an inversion centre, and is coordinated by two N atoms from two diethyl-nicotinamide ligands, two O atoms from two 4 fluoro-benzoate (PFB) ligands and two water mol-ecules in a distorted octa-hedral geometry. In the PFB ligand, the carboxyl-ate group is twisted at an angle of 2.10 (14) degrees from the attached benzene ring. In the crystal structure, inter-molecular O-H?O hydrogen bonds link mol-ecules related by translation along the a axis into chains. Weak inter-molecular C-H?O hydrogen bonds and pi-pi inter actions between the pyridine rings of neighbouring mol-ecules [centroid-to centroid distance = 3.571 (2) A] further consolidate the crystal packing. PMID- 22090920 TI - Poly[tetra-deca-aqua-tetra-kis-(MU(3)-imidazole-4,5-dicarboxyl-ato)hexa-MU(3) sulfato-cobalt(II)hexa-samarium(III)]. AB - In the title three-dimensional compound, [CoSm(6)(C(5)H(2)N(2)O(4))(4)(SO(4))(6)(H(2)O)(14)](n), the Co(II) ion is six coordinated with two O atoms and two N atoms from two imidazole-4,5-dicarboxyl ate ligands and two coordinated water mol-ecules, giving a slightly distorted octa-hedral geometry. One Sm(III) ion is eight-coordinated in a bicapped trigonal prismatic coordination geometry by four O atoms from two imidazole-4,5-dicarboxyl ate ligands, two O atoms from two SO(4) (2-) anions and two coordinated water mol ecules. The other two Sm(III) ions are nine-coordinated in a tricapped trigonal prismatic coordination geometry; one of these Sm(III) ions is bonded to four O atoms from two imidazole-4,5-dicarboxyl-ate ligands, three O atoms from three SO(4) (2-) anions and two water O atoms, and the other Sm(III) ion is coordinated by one O atom and one N atom from one imidazole-4,5-dicarboxyl-ate ligand, five O atoms from three SO(4) (2-) anions, as well as two coordinated water mol-ecules. The crystal structure is further stabilized by N-H?O, O-H?O, and C-H?O hydrogen bonding inter-actions. PMID- 22090921 TI - Tetra-MU-acetato-kappaO:O'-bis-{[2-methyl-sulfanyl-4-(pyridin-4-yl kappaN)pyrimidine]-copper(II)}(Cu-Cu). AB - The binuclear title compound, [Cu(2)(CH(3)CO(2))(4)(C(10)H(9)N(3)S)(2)], comprises a Cu(2)(CH(3)CO(2))(4) paddle-wheel core axially bound by two 2-methyl sulfanyl-4-(pyridin-4-yl)pyrimidine ligands. The complex mol-ecule has an inversion center lying at the mid-point of the Cu-Cu bond. PMID- 22090922 TI - Tetra-aqua-bis-{2-[4-(4-pyrid-yl)pyrimidin-2-ylsulfan-yl]acetato}-zinc. AB - In the title compound, [Zn(C(11)H(8)N(3)O(2)S)(2)(H(2)O)(4)], the Zn(II) ion lies on an inversion centre and is coordinated by four water mol-ecules and two N atoms from two 2-[4-(4-pyrid-yl)pyrimidin-2-ylsulfan-yl]acetate (L) ligands in a distorted octa-hedral geometry. In L, the pyridine and pyrimidine rings are twisted at an angle of 11.2 (1) degrees . The coordinated water mol-ecules and the acetate groups are involved in the formation of a three-dimensional hydrogen bonded network, which consolidates the crystal packing. PMID- 22090923 TI - Phenyl bis-(m-tolyl-amido)-phosphinate. AB - The P atom of the title compound, C(20)H(21)N(2)O(2)P, has a distorted tetra hedral configuration; the bond angles at P are in the range 96.11 (6)-117.32 (8) degrees . The N atom exhibits sp(2) character. In the crystal, mol-ecules are connected via N-H?O hydrogen bonds into bands along the a axis, consisting of R(2) (2)(8) rings. PMID- 22090924 TI - Ethyl 2-(5-cyclo-hexyl-3-methyl-sulfinyl-1-benzofuran-2-yl)acetate. AB - In the title compound, C(19)H(24)O(4)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds. The O atom of the sulfinyl group is disordered over two orientations with site-occupancy factors of 0.875 (4) and 0.125 (4). PMID- 22090925 TI - Methyl 4-[(5-chloro-pyrimidin-2-yl)carbamo-yl]benzoate. AB - Mol-ecules of the title compound, C(13)H(10)ClN(3)O(3), form centrosymmetric dimers via inter-molecular N-H?N hydrogen bonds generating an R(2) (2)(8) motif. The dimers are further connected through an O?Cl-C halogen bond [O?Cl = 3.233 (1) A and O?Cl-C = 167.33 (1) degrees ] into a chain along [110]. The secondary amide group adopts a cis conformation. Weak C-H?N hydrogen bonds among the methyl benzoate and pyrimidyl rings are also observed in the crystal structure. PMID- 22090926 TI - 2-(4-Chloro-phen-yl)naphtho-[1,8-de][1,3,2]diaza-borinane. AB - The title compound, C(16)H(12)BClN(2), is one in a series of diaza-borinanes, derived from 1,8-diaminona-phthalene, featuring substitution at the 1, 2 and 3 positions in the nitro-gen-boron heterocycle. The structure deviates from planarity, the torsion angle subtended by the p-chloro-phenyl ring relative to the nitro-gen-boron heterocycle being -44-.3(3) degrees . The mol-ecules form infinite chains with strong inter-actions between the vacant pz orbital of the B atom and the pi-system of an adjacent mol-ecule. The distance between the B atom and the 10-atom centroid of an adjacent naphthalene ring is 3.381 (4) A. One N-H H atom is weakly hydrogen bonded to the Cl atom of an adjacent mol-ecule. This combination of inter-molecular inter-actions leads to the formation of an infinite two-dimensional network perpendic-ular to the c axis. PMID- 22090927 TI - 2-[({[Bis(pyridin-2-yl)methylidene]hydrazinecarbonyl}hydrazinylidene)(pyridin-2 yl)methyl]pyridinium tetra-fluoro-borate. AB - In the title compound, C(23)H(19)N(8)O(+).BF(4) (-), one pyridine N atom is protonated. Two intra-molecular N-H?N hydrogen bonds occur. In the crystal, inter molecular N-H?N hydrogen bond links neighboring C(23)H(19)N(8)O(+) units into cyclic supra-molecular dimers while C-H?O hydrogen bonds link the C(23)H(19)N(8)O(+) units into a two-dimensional supra-molecular network structure. PMID- 22090928 TI - Oxomemazine hydro-chloride. AB - IN THE TITLE COMPOUND [SYSTEMATIC NAME: 3-(5,5-dioxo-phen-othia-zin-10-yl)-N,N,2 trimethyl-propanaminium chloride], C(18)H(23)N(2)O(2)S(+).Cl(-), the dihedral angle between the two outer aromatic rings of the phenothia-zine unit is 30.5 (2) degrees . In the crystal, the components are linked by N-H?Cl and C-H?Cl hydrogen bonds and C-H?pi inter-actions. PMID- 22090929 TI - 9-(4-Hy-droxy-phen-yl)-3,3,6,6-tetra-methyl-4,5,6,9-tetra-hydro-3H-xanthene 1,8(2H,7H)-dione. AB - In the title compound, C(23)H(26)O(4), the two cyclo-hexene rings adopt envelope conformations whereas the pyran ring adopts a boat conformation. In the crystal, pairs of inter-molecular O-H?O hydrogen bonds link the mol-ecules into inversion dimers. PMID- 22090930 TI - (E)-N'-(5-Bromo-2-hy-droxy-benzyl-idene)-3-methyl-benzohydrazide. AB - In the title mol-ecule, C(15)H(13)BrN(2)O(2), an intra-molecular O-H?N hydrogen bond influences the mol-ecular conformation; the two benzene rings form a dihedral angle of 13.6 (3) degrees . In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into chains along the a axis and weak inter molecular C-H?O hydrogen bonds further link these chains into layers parallel to the ac plane. PMID- 22090931 TI - N-(2,5-Dimethyl-phen-yl)succinamic acid monohydrate. AB - In the title compound, C(12)H(15)NO(3).H(2)O, the conformation of the N-H bond in the amide segment is syn to the ortho-methyl group and anti to the meta-methyl group in the benzene ring. Further, the conformations of the amide O and the carbonyl O atom of the acid segment are anti to the adjacent methyl-ene H atoms. The C=O and O-H bonds of the acid group are syn to one another. The structure shows an inter-esting hydrogen-bonding pattern with the water mol-ecule forming hydrogen bonds with three different mol-ecules of the compound. In the crystal, mol-ecules are packed into infinite chains through inter-molecular O-H?O and N H?O hydrogen bonds. PMID- 22090932 TI - N-(2,6-Dichloro-phen-yl)succinamic acid. AB - In the crystal of the title compound, C(10)H(9)Cl(2)NO(3), the conformations of the amide O atom and the carbonyl O atom of the acid segment are anti to each other and to the H atoms on the adjacent -CH(2) groups. The C=O and O-H bonds of the acid group are syn to one another. In the crystal, mol-ecules are packed into infinite chains through inter-molecular O-H?O and N-H?O hydrogen bonds. PMID- 22090933 TI - 2-Amino-anilinium 2-carb-oxy-acetate. AB - In the crystal structure of the title compound, C(6)H(9)N(2) (+).C(3)H(3)O(4) ( ), all the amino H atoms are involved in inter-molecular N-H?O hydrogen bonds, which link the ions into double chains parallel to [101]. In the anion, an intra molecular O-H?O hydrogen bond is observed. PMID- 22090934 TI - Ethyl 2-[(carbamoyl-amino)-imino]-propano-ate hemihydrate. AB - The title compound, C(6)H(11)N(3)O(3).0.5H(2)O, has two independent mol-ecules and one mol-ecule of water in the asymmetric unit. The crystal packing is stabilized by inter-molecular N-H?N, O-H?O, N-H?O and C-H?O hydrogen bonds. These inter-actions form a two-dimensional array in the ab plane with a zigzag motif which has an angle close to 35 degrees between the zigzag planes. The hydrogen bonding can be best described using the graph-set notation as N(1) = C(10)R(2) (2)(10)R(2) (2)(8) and N(2) = R(6) (4)(20)R(2) (2)(8). PMID- 22090935 TI - 9-[3-(Dimethyl-amino)-prop-yl]-2-trifluoro-meth-yl-9H-thioxanthen-9-ol. AB - In the title compound, C(19)H(20)F(3)NOS, the dihedral angle between the mean planes of the two benzene rings attached to the thioxanthene ring is 41.8 (7) degrees ; the latter has a slightly distorted boat conformation. The F atoms are disordered over three sets of sites [occupancy ratio = 0.564 (10):0.287 (10):0.148 (5)] and the methyl groups are disordered over two sets of sites [occupancy ratio = 0.72 (4):0.28 (4)]. The crystal packing is stabilized by O-H?N and C-H?S hydrogen bonds and weak C-H?Cg inter-actions. PMID- 22090936 TI - (E)-Ethyl N'-(3-hy-droxy-benzyl-idene)hydrazinecarboxyl-ate dihydrate. AB - The asymmetric unit of the title compound, C(10)H(12)N(2)O(3).2H(2)O, contains two organic mol-ecules with similar conformations and four water mol-ecules. Each organic mol-ecule is close to planar (r.m.s. deviations = 0.035 and 0.108 A) and adopts a trans conformation with respect to its C=N bond. In the crystal, the components are linked into a three-dimensional network by N-H?O, O-H?O, O-H?N and C-H?O hydrogen bonds, some of which are bifurcated. An R(2) (2)(8) loop occurs between adjacent organic mol-ecules. PMID- 22090937 TI - (1E,4Z,6E)-5-Hy-droxy-1,7-bis-(2-meth-oxy-phen-yl)-1,4,6-hepta-trien-3-one. AB - In the title compound, C(21)H(20)O(4), the central hepta-trienone unit is approximately planar, with a maximum atomic deviation of 0.1121 (11) A; the two benzene rings are twisted with respect to the hepta-trienone mean plane by 2.73 (5) and 29.31 (4) degrees . The mol-ecule exists in the enol form and the hy droxy group forms an intra-molecular hydrogen bond with the neighboring carbonyl group. Weak inter-molecular C-H?O hydrogen bonding is present in the crystal structure. PMID- 22090938 TI - (E)-N'-(4-Meth-oxy-benzyl-idene)-3-nitro-benzohydrazide. AB - In the title compound, C(15)H(13)N(3)O(4), the two substituted benzene rings form a dihedral angle of 5.0 (3) degrees . In the crystal, inter-molecular N-H?O hydrogen bonds link mol-ecules into chains along the b axis. PMID- 22090939 TI - Methyl 2-amino-5-bromo-benzoate. AB - In the title compound, C(8)H(8)BrNO(2), the dihedral angle between the aromatic ring and the methyl acetate side chain is 5.73 (12) degrees . The mol-ecular conformation is stabilized by an intra-molecular N-H?O hydrogen bond, generating an S(6) ring. In the crystal, mol-ecules are connected by N-H?O inter-actions, generating zigzag chains running along the b-axis direction. PMID- 22090940 TI - tert-Butyl N-((1S)-2-hy-droxy-1-{N'-[(E)-2-hy-droxy-4-meth-oxy-benzyl idene]hydrazinecarbon-yl}eth-yl)carbamate. AB - The mol-ecule of the title compound, C(16)H(23)N(3)O(6), is twisted about the chiral C atom with the dihedral angle formed between the amide residues being 76.9 (3) degrees . Overall, the mol-ecule is curved with the terminal organic groups lying to the same side. The conformation about the imine bond [1.291 (5) A] is E and an intra-molecular O-H?N hydrogen bond generates an S(6) ring. In the crystal, O-H?O and N-H?O hydrogen bonds involving the hy-droxy, amine and carbonyl groups lead to the formation of supra-molecular layers, which stack along the c-axis direction. PMID- 22090941 TI - 2-Hy-droxy-methyl-1,3-dimethyl-imidazolium iodide. AB - The crystal packing of the title compound, C(6)H(11)N(2)O(+).I(-), can be described as inter-calated layers lying parallel to (010), with the iodide ions located between the cations. A weak intra-molecular C-H?O hydrogen bond occurs within the cation. In the crystal, inter-molecular O-H?I hydrogen bonds result in the formation of a three-dimensional network and reinforce the cohesion of the ionic structure. PMID- 22090942 TI - 1-(4-Chloro-benzo-yl)-3-cyclo-hexyl-3-methyl-thio-urea. AB - In the title compound, C(15)H(19)ClN(2)OS, the dihedral angle between the amide and thio-urea fragments is 58.07 (17) degrees . The cyclo-hexane group adopts a chair conformation and is twisted relative to the thio-urea fragment, forming a dihedral angle of 87.32 (18) degrees . In the crystal, N-H?S hydrogen bond links the mol-ecules into chains running parallel to the a-axis direction. PMID- 22090943 TI - 3,3'',4,4''-Tetra-meth-oxy-1,1':4',1''-terphen-yl. AB - The title mol-ecule, C(22)H(22)O(4), is centrosymmetric with an inversion centre located at the centre of the benzene ring. The 3,4-dimeth-oxy-benzene fragment is essentially planar [maximum deviation = 0.400 (2) A] and twisted relative to the central benzene ring, forming a dihedral angle of 21.25 (7) degrees . In the crystal, C-H?O hydrogen bonds link the mol-ecules into a two-dimensional polymeric structure lying parallel to (100). PMID- 22090944 TI - 2-Amino-anilinium 6-carb-oxy-picolinate monohydrate. AB - In the title compound, C(6)H(9)N(2) (+).C(7)H(4)NO(4) (-).H(2)O, one amino group of diamino-benzene is protonated while one carb-oxy group of pyridine-2,6-dicarb oxy-lic acid is deprotonated. In the anion, the CO(2) and CO(2)H groups make dihedral angles of 4.0 (5) and 8.7 (4) degrees with the pyridine ring. In the crystal, extensive N-H?O, N-H?N and O-H?O hydrogen bonds occur between anions, cations and water mol-ecules. PMID- 22090945 TI - 5,5'-[(2,4-Dichloro-phen-yl)methyl-ene]bis-(2,2-dimethyl-1,3-dioxane-4,6-dione). AB - The title compound, C(19)H(18)Cl(2)O(8), was prepared by the reaction of 2,2 dimethyl-1,3-dioxane-4,6-dione and 2,4-dichloro-benzaldehyde in ethanol. The two 1,3-dioxane rings exhibit boat conformations. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O and C-H?Cl hydrogen bonds, forming chains parallel to the a axis. PMID- 22090946 TI - (E)-N'-(2-Meth-oxy-benzyl-idene)-3-nitro-benzohydrazide. AB - In the title compound, C(15)H(13)N(3)O(4), the two substituted benzene rings form a dihedral angle of 10.9 (3) degrees . In the crystal, inter-molecular C-H?O and N-H?O hydrogen bonds link mol-ecules into chains running parallel to [101]. PMID- 22090947 TI - 4-Dimethyl-amino-N'-(2-meth-oxy-benzyl-idene)benzohydrazide. AB - In the title mol-ecule, C(17)H(19)N(3)O(2), the dihedral angle between the two benzene rings is 14.05 (15) degrees . In the crystal, mol-ecules are linked through inter-molecular N-H?O hydrogen bonds, forming chains along b. PMID- 22090948 TI - Bis(2-hy-droxy-phen-yl)methanone. AB - In the title compound, C(13)H(10)O(3), a benzophenone derivative, the least squares planes defined by the C atoms of the 2-hy-droxy-phenyl rings inter-sect at an angle of 45.49 (3) degrees . The substituents on the aromatic systems are both orientated towards the central O atom. Intra- as well as inter-molecular O H?O hydrogen bonds are observed, the latter giving rise to the formation of centrosymmetric dimers. The closest centroid-centroid distance between two pi systems is 3.7934 (7) A. PMID- 22090949 TI - 1-(4-Methyl-phenyl-sulfon-yl)-5-phenyl-4,5-dihydro-1H-pyrazole. AB - The title compound, C(16)H(16)N(2)O(2)S, was synthesized by the reaction of 5 phenyl-4,5-dihydro-1H-pyrazole and 4-methyl-benzene-1-sulfonyl chloride. The five membered pyrazoline ring is nearly planar, with a miximum deviation of 0.078 (2) A. PMID- 22090950 TI - 1,4-Bis[(2-ethyl-1H-benzimidazol-1-yl)meth-yl]benzene. AB - In the title mol-ecule, C(26)H(26)N(4), the central benzene ring forms dihedral angles of 89.9 (2) and 85.4 (2) degrees with the two benzimidazole rings. PMID- 22090951 TI - rac-2-Amino-pyridinium cis-2-carb-oxy-cyclo-hexane-1-carboxyl-ate. AB - In the structure of the title compound, C(5)H(7)N(2) (+).C(8)H(11)O(4) (-), the cis anions associate through head-to-tail carb-oxy-lic acid-carboxyl O-H?O hydrogen bonds [graph set C(7)], forming chains which extend along c and are inter-linked through the carboxyl groups, forming cyclic R(2) (2)(8) associations with the pyridinium and an amine H-atom donor of the cation. Further amine carboxyl N-H?O inter-actions form enlarged centrosymmetric rings [graph set R(4) (4)(18)] and extensions down b, giving a three-dimensional structure. PMID- 22090952 TI - 6-Hy-droxy-2,5,7,8-tetra-methyl-3,4-dihydro-2H-1-benzopyran-2-carbonitrile, from synchrotron data. AB - The crystal structure of the title compound, C(14)H(17)NO(2), solved and refined against synchrotron diffraction data, contains one formula unit in an asymmetric unit. In the crystal, mol-ecules form right-handed helices located at the 2(1) screw axis parallel to the a-axis direction, generated by O-H?N hydrogen bonding between the hy-droxy group and carbonitrile group of an adjacent mol-ecule. PMID- 22090953 TI - 2-(4-Bromo-phen-yl)-3-(4-hy-droxy-phen-yl)-1,3-thia-zolidin-4-one. AB - In the title compound, C(15)H(12)BrNO(2)S, the dihedral angle between the two aromatic rings is 87.81 (8) degrees . The five-membered thia-zolidine ring has an envelope conformation, with the S atom displaced by 0.4545 (7) A from the mean plane of the other four ring atoms. The crystal structure exhibits O-H?O, C-H?O, C-H?Br and C-H? pi inter-actions. PMID- 22090954 TI - 4,4'-Di-tert-butyl-2,2'-dipyridinium dichloride. AB - In the title compound, C(18)H(26)N(2) (2+).2Cl(-), the complete dication is generated by crystallographic inversion symmetry; both N atoms are protonated and engaged in strong and highly directional N-H?Cl hydrogen bonds. Additional weak C H?Cl contacts promote the formation of a tape along ca. [110]. The crystal structure can be described by the parallel packing of these tapes. The crystal studied was a non-merohedral twin with twin law [-1 0 0, 0 -1 0, -0.887 0.179 1] and the final BASF parameter refining to 0.026 (2) . PMID- 22090955 TI - N-Hy-droxy-pyridine-4-carboxamide. AB - The title compound, C(6)H(6)N(2)O(2), is approximately planar with an r.m.s. deviation for the non-H atoms of 0.052 A. In the crystal, a two-dimensional array in the bc plane is stabilized by O-H?N and N-H?O hydrogen bonds. PMID- 22090956 TI - 2-Hy-droxy-2,3,5,10,11,11a-hexa-hydro-1H-pyrrolo-[2,1-c][1,4]benzodiazepine-5,11 dione. AB - The seven-membered ring of the title compound, C(12)H(12)N(2)O(3), which is fused with the phenyl-ene ring, adopts a boat-shaped conformation (with the methine C atom as the prow and the phenyl-ene C atoms as the stern); the H atom on the methine linkage exists in an axial position. The five-membered ring that is fused with the seven-membered ring adopts an envelope conformation (with the C atom bearing the hy-droxy substituent representing the flap) [the deviation from the plane defined by the other four atoms is 0.200 (7) A in one mol-ecule and 0.627 (5) A in the other]. The two independent mol-ecules are disposed about a pseudo center of inversion and are connected by a pair of N-H?O hydrogen bonds. Adjacent dimers are linked by a pair of O-H?O hydrogen bonds, generating a chain running along the b axis. PMID- 22090957 TI - 4,8-Dimeth-oxy-furo[2,3-b]quinoline (gamma-fagarine). AB - The title mol-ecule, C(13)H(11)NO(3), a natural compound extracted from Phellodendron chinense, exhibits a near planar framework: the mean deviations from the furo[2,3-b]quinoline ring system and from the whole mol-ecule (not including the H atoms) are 0.006 and 0.062 A, respectively. PMID- 22090958 TI - Bis(8-methyl-2,8-dicarba-closo-dodeca-boran-2-yl) tris-elenide. AB - In the title compound, C(6)H(26)B(20)Se(3), the geometry around the central Se atom is V-shaped, with the Se-Se-Se angle being 105.60 (4) degrees . The Se-Se bond lengths are consistent with single covalent bonds. PMID- 22090959 TI - N-Ethyl-4-methyl-N-(3-methyl-phen-yl)benzene-sulfonamide. AB - The title compound, C(16)H(19)NO(2)S, crystallizes with two crystallographically independent mol-ecules in the asymmetric unit in which the dihedral angles between the planes defined by the aromatic rings are 35.3 (2) and 42.5 (2) degrees . In the crystal, inter-molecular C-H?O hydrogen bonds stabilize the packing. PMID- 22090960 TI - Ethyl 3-(4-chloro-phen-yl)-1-(2-oxo-2-phenyl-eth-yl)-1H-pyrazole-5-carboxyl-ate. AB - In the title compound, C(20)H(17)ClN(2)O(3), the dihedral angles between the pyrazole ring and the substituted and unsubstituted benzene rings are 3.64 (13) and 81.15 (17) degrees , respectively. Mol-ecules are connected via three pairs of weak hydrogen bonds into a centrosymmetric dimer. The crystal structure is stabilized by inter-molecular C-H?O and C-H?pi inter-actions. PMID- 22090961 TI - 3-Hy-droxy-N'-[(E)-3-pyridyl-methyl-idene]-2-naphtho-hydrazide. AB - The title compound, C(17)H(13)N(3)O(2), displays an E configuration about the C=N bond. The mean planes of the pyridine and benzene rings make a dihedral angle of 31.2 (2) degrees . An intra-molecular O-H?O hydrogen bond is observed. In the crystal, inter-molecular N-H?N hydrogen bonding links the mol-ecules into a chain along [101]. PMID- 22090962 TI - Methyl (2Z)-2-(2-fluoro-4-meth-oxy-benzyl-idene)-5-(4-meth-oxy-phen-yl)-7-methyl 3-oxo-2,3-dihydro-5H-[1,3]thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate. AB - The asymmetric unit of the title compound, C(24)H(21)FN(2)O(5)S, consists of two crystallographically independent mol-ecules. In each mol-ecule, the central dihydro-pyrimidine ring is significantly puckered and adopts a conformation which is best described as an inter-mediate between a boat and a screw boat. The least squares planes of the dihydro-pyrimidine rings are almost coplanar with the fluoro-substituted benzene rings, making dihedral angles of 9.04 (7) and 6.68 (7) degrees , and almost perpendicular to the meth-oxy-substituted benzene rings with dihedral angles of 89.23 (7) and 88.30 (7) degrees . In the mol-ecular structure, S(6) ring motifs are formed by C-H?O and C-H?S hydrogen bonds. In the crystal, mol-ecules are linked into a three-dimensional network by inter-molecular C-H?O and C-H?F hydrogen bonds. The crystal structure is further stabilized by a C-H?pi inter-action. PMID- 22090963 TI - (5E)-5-(4-Meth-oxy-benzyl-idene)-2-(piperidin-1-yl)-1,3-thia-zol-4(5H)-one. AB - In the title compound, C(16)H(18)N(2)O(2)S, the piperidine ring adopts a chair conformation. The central 4-thia-zolidinone ring makes dihedral angles of 12.01 (7) and 51.42 (9) degrees , respectively, with the benzene ring and the least squares plane of the piperidine ring. An intra-molecular C-H?S hydrogen bond stabilizes the mol-ecular structure and generates an S(6) ring motif. In the crystal, mol-ecules are linked into a tape along the c axis by inter-molecular C H?O hydrogen bonds. PMID- 22090964 TI - Redetermination and absolute configuration of pruniflorone M monohydrate. AB - THE TITLE XANTHONE KNOWN AS PRUNIFLORONE M (SYSTEMATIC NAME: (2R)-5,10-dihy-droxy 2-hy-droxy-methyl-1,1-dimethyl-1H-furo[2,3-c]xanthen-6-one), crystallized in a monohydrate form, C(18)H(16)O(6).H(2)O. It was isolated from the green fruits of Cratoxylum formosum ssp. pruniflorum. The structure of the title compound has been reported previously [Boonnak et al. (2010 ?). Aust. J. Chem. 63, 1550-1556], but we report here the absolute configuration determined using Cu Kalpha radiation. There are two crystallograpically independent mol-ecules in the asymmetric unit, which differ slightly in the bond angles. The hy-droxy-methyl substituents at position 2 of the furan rings of both pruniflorone M mol-ecules adopt R configurations. In both mol-ecules, the three rings of the xanthone skeleton are approximately coplanar, with an r.m.s. deviation of 0.0124 (2) A for one mol-ecule and 0.0289 (2) A for the other, and the furan ring adopts an envelope conformation. In the crystal, mol-ecules of pruniflorone M and water are linked into a two-dimensional network by O-H?O hydrogen bonds and weak C-H?O inter-actions. The crystal structure is further consolidated by pi-pi inter actions with centroid-centroid distances in the range 3.5987 (13)-3.7498 (14) A. Short C?C [3.378 (3) A] and O?O [2.918 (3) A] contacts are also observed. PMID- 22090965 TI - Ethyl 1-benzyl-3-(4-bromo-phen-yl)-1H-pyrazole-5-carboxyl-ate. AB - In the title compound, C(19)H(17)BrN(2)O(2), the pyrazole ring makes dihedral angles of 88.00 (16) and 5.78 (13) degrees with the phenyl and bromo-phenyl rings, respectively. In the crystal, mol-ecules are linked by weak inter molecular C-H?O hydrogen bonds. PMID- 22090966 TI - 9-Phenyl-3,6-bis-(4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole. AB - In the title compound, C(30)H(35)B(2)NO(4), the carbazole skeleton is essentially planar (r.m.s. deviation for all non-H atoms = 0.035 A), and is oriented at a dihedral angle of 65.0 (3) degrees with respect to the adjacent phenyl ring. PMID- 22090967 TI - 2,2,6,6-Tetra-methyl-4-oxopiperidin-1-ium 4-chloro-3-nitro-benzoate. AB - The title salt, C(9)H(18)NO(+).C(7)H(3)ClNO(4) (-), was obtained as an unexpected product of the reaction of 4-chloro-3-nitro-benzoyl isothio-cyanate with pyrrolidine. The six-membered ring of the 4-oxopiperidinium cation adopts a chair conformation. In the crystal structure, two cations and three anions are linked together by inter-molecular N-H?O and C-H?O hydrogen bonds and arranged diagonally along the ac face. PMID- 22090968 TI - 2,4,6-Trimethyl-anilinium 2-carb-oxy-ethano-ate. AB - The anion of the title molecular salt, C(9)H(14)N(+).C(3)H(3)O(4) (-), features an intra-molecular O-H?O hydrogen bond. In the crystal, inter-molecular N-H?O inter-actions link each cation to three different anions. PMID- 22090969 TI - 3-(4-Amino-3-ethyl-5-sulfanyl-idene-4,5-dihydro-1H-1,2,4-triazol-1-yl)-3-(2 chloro-phen-yl)-1-phenyl-propan-1-one. AB - In the title mol-ecule, C(19)H(19)ClN(4)OS, the 1,2,4-triazole ring forms dihedral angles of 86.0 (2) and 65.6 (2) degrees with the phenyl and chloro phenyl rings, respectively. In the crystal, inter-molecular N-H?S and N-H?O hydrogen bonds link mol-ecules into centrosymmetric dimers, which are further linked into chains in [001] via weak C-H?pi inter-actions. PMID- 22090970 TI - Bis(4-pyrid-yl) disulfide-2,2'-[(p-phenyl-enebis(-oxy)]diacetic acid (1/1). AB - The asymmetric unit of the title 1:1 co-crystal, C(10)H(8)N(2)S(2).C(10)H(10)O(6), comprises two half-mol-ecules, the bis-(4-pyrid yl) disulfide having twofold rotational symmetry and the 2,2'-[(p-phenyl-enebis( oxy)]diacetic acid having crystallographic inversion symmetry. In the disulfide mol-ecule, the dihedral angle between the two pyridine rings is 86.8 (1) degrees , while the carboxyl groups of the substituted quinone lie essentially in the plane of the benzene ring [dihedral angle = 5.3 (1) degrees ]. In the crystal, the components are linked via inter-molecular O-H?N hydrogen bonds into zigzag chains which extend along c and are inter-linked through C-H?pi associations. PMID- 22090971 TI - 5-(Pyridin-4-ylmeth-yl)-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one. AB - In the title compound, C(11)H(9)N(5)O, the pyrazolo-pyrimidin-4-one ring system is almost planar, with a maximum deviation of 0.0546 (13) A for the O atom. The crystal packing is stabilized by inter-molecular N-H?N, C-H?O and C-H?N hydrogen bonds. In addition, pi-pi stacking is found between the pyridine ring and the pyrazolo-pyrimidin-4-one ring systems, with centroid-centroid distances in the range 3.9627 (12)-4.6781 (12) A. PMID- 22090972 TI - 3,8-Dimethyl-quinazoline-2,4(1H,3H)-dione. AB - In the title compound, C(10)H(10)N(2)O(2), all non-H atoms are approximately co planar with an r.m.s. deviation of 0.016 A. In the crystal, mol-ecules are linked into inversion dimers by pairs of N-H?O hydrogen bonds. Chains along [010] are buiilt up by pi-pi inter-actions [centroid-centroid distance = 3.602 (1) A] between the benzene and piperazine rings of adjacent mol-ecules. PMID- 22090973 TI - 2-(4-Iodo-phen-oxy)acetamide. AB - The mol-ecule of the title compound, C(8)H(8)INO(2), amide-typical resonance shortens the nominal C-N single bond to 1.322 (7) A. In the crystal, hydrogen bonds involving both nitro-gen-bound H atoms as well as C-H?O contacts connect the mol-ecules into double layers approximately perpendicular to the crystallographic b axis. No pi-stacking is apparent in the crystal structure. PMID- 22090974 TI - 4,7,13,18-Tetra-oxa-1,10-diazo-nia-bicyclo-[8.5.5]icosane bis-(hexa-fluorido phosphate). AB - The asymmetric unit of the title structure, C(14)H(30)N(2)O(4) (2+).2PF(6) (-), contains the anion and half of the cation, the latter being completed by a crystallographic twofold axis. The cation has a cage structure with the ammonium H atoms pointing into the cage. These H atoms are shielded from inter-molecular inter-actions and form only intra-molecular contacts. There are short inter molecular C-H?F inter-actions in the structure, but no conventional inter molecular hydrogen bonds. PMID- 22090975 TI - 3,3'-Di-n-propyl-1,1'-[p-phenyl-enebis(methyl-ene)]diimidazolium dibromide. AB - The asymmetric unit of the title compound, C(20)H(28)N(4) (2+).2Br(-), consists of half a 3,3'-di-n-propyl-1,1'-[p-phenyl-enenis(methyl-ene)]diimidazolium cation and a bromide anion. The cation is located on an inversion center and adopts an ?AAA? trans conformation. In the crystal, the cation is linked to the anions via weak C-H?Br hydrogen bonds. PMID- 22090976 TI - N-[(E)-4-Chloro-benzyl-idene]-2,4-dimethyl-aniline. AB - The title mol-ecule, C(15)H(14)ClN, exists in a trans configuration with respect to the C=N bond [1.2813 (16) A]. The dihedral angle between the benzene rings is 52.91 (6) degrees . The crystal structure is stabilized by weak inter-molecular C H?pi inter-actions. PMID- 22090977 TI - 2-[(E)-(2,4-Dimethyl-phen-yl)imino-meth-yl]phenol. AB - The asymmetric unit of the title compound, C(15)H(15)NO, contains two independent mol-ecules, both of which exist in trans configurations with respect to the C=N bonds [1.278 (2) and 1.279 (2) A]. In each mol-ecule, intra-molecular O-H?N hydrogen bonds generate S(6) ring motifs. In one mol-ecule, the benzene rings form a dihedral angle of 13.38 (9) degrees , while in the other mol-ecule the dihedral angle is 30.60 (10) degrees . In the crystal, the two independent mol ecules are linked via weak inter-molecular C-H?O hydrogen bonds. PMID- 22090978 TI - 2-[(E)-(2,4,6-Trichloro-phen-yl)imino-meth-yl]phenol. AB - The title mol-ecule, C(13)H(8)Cl(3)NO, exists in a trans configuration with respect to the C=N bond [1.278 (2) A]. The benzene rings form a dihedral angle of 24.64 (11) degrees . The mol-ecular structure is stabilized by an intra-molecular O-H?N hydrogen bond, which generates an S(6) ring motif. In the crystal, pi-pi stacking inter-actions [centroid-centroid distances = 3.6893 (14) A] are observed. PMID- 22090979 TI - 2-(m-Tol-yloxy)benzoic acid. AB - In the crystal structure of the title compound, C(14)H(12)O(3), the mol-ecules form classical O-H?O hydrogen-bonded carb-oxy-lic acid dimers. The dihedral angle between the two rings is 80.9 (3) degrees . PMID- 22090980 TI - Methyl 2-{[(2-fur-yl)(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl idene)meth-yl]amino}-acetate. AB - In the title compound, C(18)H(17)N(3)O(4), the amino group of the glycine methyl ester fragment is involved in an intra-molecular N-H?O hydrogen bond. The phenyl and furyl rings form dihedral angles of 10.20 (4) and 54.56 degrees , respectively, with the pyrazole ring. In the crystal, mol-ecules related by translation along the b axis are linked into chains via weak inter-molecular C H?O hydrogen bonds. PMID- 22090981 TI - 2,2-Dimethyl-5-(2,3,4-trimeth-oxy-benzyl-idene)-1,3-dioxane-4,6-dione. AB - The title compound, C(16)H(18)O(7), was prepared by the reaction of 2,2-dimethyl 1,3-dioxane-4,6-dione and 2,3,4-trimeth-oxy-benzaldehyde. The 1,3-dioxane ring is in a slightly distorted boat conformation. The crystal structure is stabilized by weak inter-molecular C-H?O hydrogen bonds. PMID- 22090982 TI - 1,2-Bis(4-nitro-benz-yl)diselane. AB - The title compound, C(14)H(12)N(2)O(4)Se(2), is not chiral, but the mol-ecules assume a chiral conformation in the solid state and crystallize as an aggregate. The central C-Se-Se-C torsion angle is 90.4 (2) degrees , while the two Se-Se-C-C fragments assume gauche conformations with values of -59.4 (5) and 67.5 (4) degrees . The dihedral angle between the two benzene rings is 80.74 (14) degrees . PMID- 22090983 TI - (S)-2-[(S,Z)-3-Bromo-1-nitro-4-phenyl-but-3-en-2-yl]cyclo-hexa-none. AB - In the crystal structure of the title compound, C(16)H(18)BrNO(3), the two stereogenic centres both have an S configuration. The cyclo-hexyl ring adopts a chair conformation. In the crystal, mol-ecules are linked by weak N-O?Br contacts [O?Br = 3.289 (4) A]. PMID- 22090984 TI - 1-Cyano-N-(2,4,5-trichloro-phen-yl)cyclo-propane-1-carboxamide. AB - In the title compound, C(11)H(7)Cl(3)N(3)O, the dihedral angle between the benzene and cyclo-propane rings is 85.8 (2) degrees . In the crystal, mol-ecules are linked by C-H?O inter-actions, generating C(5) chains propagating in the a axis direction. PMID- 22090985 TI - Methyl 6-azido-6-de-oxy-alpha-d-galactoside. AB - The structure of the title compound, C(7)H(13)N(3)O(5), was solved using data from a multiple fragment crystal. The galactoside ring adopts a (4)C(1) chair conformation. In the crystal, the molecules are linked by strong O-H?O hydrogen bonds, which build linkages around the screw axis of the cell in a similar way to the iodo analogue. These C-5 and C-6 packing motifs expand to R(2) (2)(10), C(2) (2)(7) and C(2) (2) (2)(8) motifs, as found in closely related compounds. PMID- 22090986 TI - 3-{1-[4-(2-Methyl-prop-yl)phen-yl]eth-yl}-4-phenyl-1H-1,2,4-triazole-5(4H) thione. AB - In the title compound, C(20)H(23)N(3)S, the central 1,2,4-triazole ring makes dihedral angles of 69.76 (9) and 81.69 (8) degrees , respectively, with the phenyl and benzene rings. In the crystal, mol-ecules are linked into a centrosymmetric dimer by a pair of inter-molecular N-H?S hydrogen bonds, generating an R(2) (2)(8) ring motif. PMID- 22090987 TI - 4-{[(E)-(3-Phenyl-1H-pyrazol-4-yl)methyl-idene]amino}-1H-1,2,4-triazole-5(4H) thione. AB - In the title compound, C(12)H(10)N(6)S, a weak intra-molecular C-H?S hydrogen bond stabilizes the mol-ecular conformation. The pyrazole and triazole rings form a dihedral angle of 17.82 (8) degrees . The mol-ecule adopts an E configuration with respect to the central C=N double bond. In the crystal, inter-molecular N H?N and N-H?S hydrogen bonds link mol-ecules into chains propagating in [20[Formula: see text]]. PMID- 22090988 TI - 2,2'-Bipyridine-cyclo-pentane-1,2,3,4-tetra-carb-oxy-lic acid (1/1). AB - The asymmetric unit of the title compound, C(10)H(8)N(2).C(9)H(10)O(8), contains a half-molecule of 2,2'-bipyridine and a half-molecule of 1,2,3,4 cyclopentanetetracarboxylic acid, both components being completed by crystallographic inversion symmetry. In the crystal, the mol-ecules are assembled into chains extending along [010] by O-H?N hydrogen bonds; adjacent chains are linked by O-H?O hydrogen bonds into a three-dimensional network. PMID- 22090989 TI - Diethyl 2-{[(4-meth-oxy-3-pyrid-yl)amino]-methyl-idene}malonate. AB - In the title mol-ecule, C(14)H(8)N(2)O(5), the amino group is involved in the formation an intra-molecular N-H?O hydrogen bond. In the crystal, weak inter molecular C-H?O and C-H?N hydrogen bonds link the mol-ecules into ribbons along the b axis. PMID- 22090990 TI - 3-(3-Meth-oxy-benzo-yl)-1,1-diphenyl-thio-urea. AB - The thiono and carbonyl groups in the title compound, C(21)H(18)N(2)O(2)S, adopt an anti disposition with respect to the central C-N bond. The diphenyl-amine rings are twisted relative to each other by a dihedral angle of 82.55 (10) degrees . The 3-meth-oxy-benzoyl fragment is twisted relative to one of the diphenyl-amine rings, forming a dihedral angle of 74.04 (9) degrees . In the crystal, pairs of inter-molecular N-H?S hydrogen bonds link the mol-ecules into centrosymmetric dimers, forming columns parallel to the a axis. PMID- 22090991 TI - 6-(4-Chloro-phen-yl)-2-(4-meth-oxy-phen-yl)-6,7-dihydro-4H-pyrazolo-[5,1 c][1,4]oxazine. AB - In the title compound, C(19)H(17)ClN(2)O(2), the pyrazole ring is almost planar with a maximum deviation of 0.009 (3) A and makes a dihedral angle of 8.96 (9) degrees with the oxazine ring. The dihedral angles between the pyrazole ring and the chlorine- and meth-oxy-substituted benzene rings are 50.95 (8) and 13.24 (9) degrees , respectively. An inter-molecular C-H?N hydrogen bond links the mol ecules into infinite chains along the a axis. The crystal structure is further stabilized by C-H?pi inter-actions. PMID- 22090992 TI - Ethyl-triphenyl-phospho-nium bromide dihydrate. AB - In the crystal structure of the title hydrated bromide salt, C(20)H(20)P(+).Br( ).2H(2)O, O-H?Br and O-H?O hydrogen bonds as well as C-H?Br contacts connect the different components into a three-dimensional network. In the cation, the aromatic rings make dihedral angles of 55.24 (5), 76.16 (4) and 85.68 (4) degrees . PMID- 22090993 TI - 1-Diazo-naphthalen-2(1H)-one. AB - The mol-ecule of the title compound, C(10)H(6)N(2)O, is nearly planar [maximum deviation = 0.030 (1) A]. The CN(2) moiety is almost linear, with a C-N-N angle of 175.50 (14) degrees . A single inter-molecular C-H?O hydrogen bond is observed in the crystal structure. A pi-pi inter-action is also observed with the shortest distance being 3.6832 (12) A between the the centroids of the six-membered rings. PMID- 22090994 TI - Clostebol acetate. AB - The title compound, C(21)H(29)ClO(3) [systematic name (8R,9S,10R,13S,14S,17S)-4 chloro-3-oxoandrost-4-en-17beta-yl acetate], is a 4-chloro derivative of testosterone, used as an anabolic androgenic agent or applied topically in ophthalmological and dermatological treatments. The absolute configurations at positions 8, 9, 10, 13, 14 and 17 were established by refinement of the Flack parameter as R, S, R, S, S, and S, respectively. Rings B and C of the steroid ring system adopt chair conformations, ring A has a half-chair conformation, while ring D is in a C(13) envelope conformation. Ring B and C, and C and D are trans fused. In the crystal, molecules are linked by a weak C-H?O interaction. PMID- 22090995 TI - 1,3-Bis(4-fluoro-phen-yl)-N,N'-(propane-1,3-diyl-idene)dihydroxyl-amine. AB - The title compound, C(15)H(12)F(2)N(2)O(2), crystallizes with two mol-ecules (A and B) in the asymmetric unit. Both aromatic rings of both mol-ecules are disordered over two orientations [occupancy ratios of 0.768 (3):0.232 (3) and 0.770 (3):0.230 (3) for mol-ecule A and 0.789 (3):0.211 (3) and 0.789 (3):0.211 (3) for mol-ecule B]. The dihedral angles between the planes of the major and minor components of the disordered aromatic rings are 72.0 (4) and 71.2 (4) degrees for mol-ecule A, and 70.2 (4) and 71.5 (2) degrees for mol-ecule B. In the crystal, both mol-ecules form inversion dimers with R(2) (2)(6) ring motifs via pairs of inter-molecular O-H?N hydrogen bonds. The dimers are linked, forming zigzag C(7) chains along the c axis. Weak C-H?pi inter-actions help to consolidate the packing. PMID- 22090996 TI - (E)-Methyl N'-[(1H-indol-3-yl)methyl-idene]hydrazinecarboxyl-ate 0.25-hydrate. AB - The asymmetric unit of the title compound, C(11)H(11)N(3)O(2).0.25H(2)O, contains two independent organic mol-ecules and a water mol-ecule, which lies on a twofold rotation axis. The side chains of the two mol-ecules have slightly different orientations, the C=N-N-C torsion angle being -163.03 (15) degrees in one and 177.52 (14) degrees in the other, with each adopting a trans configuration with respect to the C=N bond. In the crystal, mol-ecules are linked into chains extending along b by N-H?O, O-H?N and O-H?O hydrogen bonds and in addition, four inter-molecular C-H?pi inter-actions are present. PMID- 22090997 TI - 2-(5-Cyclo-hexyl-3-methyl-sulfanyl-1-benzofuran-2-yl)acetic acid. AB - In the title compound, C(17)H(20)O(3)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, the carboxyl groups are involved in inter-molecular O-H?O hydrogen bonds, which link the mol-ecules into centrosymmetric dimers. These dimers are further stabilized by weak inter-molecular C-H?O hydrogen bonds. In addition, the crystal structure also exhibits aromatic pi-pi inter-actions between the furan rings of adjacent mol-ecules [centroid-centroid distance = 3.505 (2) A, inter-planar distance = 3.385 (2) A and slippage = 0.909 (2) A], and inter-molecular C-H?pi inter-actions. PMID- 22090998 TI - 4,7,13,18-Tetra-oxa-1,10-diazo-nia-bicyclo-[8.5.5]icosane hexa-fluorido-silicate. AB - The asymmetric unit of the title molecular salt, C(14)H(30)N(2)O(4) (2+).SiF(6) (2-), contains half of both the anion and the cation, both ions being completed by a crystallographic twofold axis passing through the Si atom. The cation has a cage structure with the ammonium H atoms pointing into the cage. These H atoms are shielded from inter-molecular inter-actions and form only intra-molecular contacts. There are short inter-molecular C-H?F inter-actions in the structure, but no conventional inter-molecular hydrogen bonds. PMID- 22090999 TI - trans-3,3',4,5'-Tetra-meth-oxy-stilbene. AB - The title compound, C(18)H(20)O(4), was synthesized by a Wittig-Horner reaction of diethyl 3,4-dimeth-oxy-benzyl-phosphate and 3,5-dimeth-oxy-benzaldehyde. In the crystal, the dihedral angle between the two aromatic rings is 2.47 (12) degrees . All the meth-oxy groups are almost coplanar with the aromatic ring to which they are attached [C-C-O-C torsion angles = -2.8 (3), -5.2 (4), -176.3 (2) and -178.0 (2) degrees ]. PMID- 22091000 TI - 1-Chloro-1-[(4-meth-oxy-phen-yl)hydrazinyl-idene]propan-2-one. AB - The non-H atoms of the title compound, C(10)H(11)ClN(2)O(2), lie nearly on a plane (r.m.s. deviation = 0.150 A), and the C=N double bond has a Z configuration. In the crystal, adjacent mol-ecules are linked by an N-H?O(carbon yl) hydrogen bond, forming a chain running along [201]. PMID- 22091001 TI - 1-Chloro-1-[(4-chloro-phen-yl)hydrazinyl-idene]propan-2-one. AB - The non-H atoms of the title compound, C(9)H(8)Cl(2)N(2)O, lie nearly on a plane (r.m.s. deviation = 0.110 A), and the C=N double bond has a Z configuration. In the crystal, adjacent mol-ecules are linked by an N-H?O(carbon-yl) hydrogen bond, forming a chain running along [100]. PMID- 22091002 TI - 1-Chloro-1-[(4-nitro-phen-yl)hydrazinyl-idene]propan-2-one. AB - The non-H atoms of the title compound, C(9)H(8)ClN(3)O(3), lie approximately on a plane (r.m.s. deviation = 0.111 A), and the C=N double bond has a Z configuration. In the crystal, adjacent mol-ecules are linked by an N-H?O(carbon yl) hydrogen bond, forming a chain running along [101]. PMID- 22091003 TI - 1-Chloro-1-[(4-methyl-phen-yl)hydrazinyl-idene]propan-2-one. AB - The asymmetric unit of the title compound, C(10)H(11)ClN(2)O, contains two mol ecules. The non-H atoms of each mol-ecule lie approximately on a plane (r.m.s. deviations = 0.062 and 0.110 A), and the C=N double bond has a Z-configuration in both independent mol-ecules. In the crystal, adjacent mol-ecules are linked by N H?O(carbon-yl) hydrogen bonds, forming chains running along [100]. PMID- 22091004 TI - 2-(4-Fluoro-phen-yl)-1-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline monohydrate. AB - In the title compound, C(25)H(15)FN(4).H(2)O, the fused ring system is essentially planar [maximum deviation of 0.0822 (14) A]. The imidazole ring makes dihedral angles of 76.83 (7) and 32.22 (7) degrees with the phenyl group attached to nitro-gen and the fluoro-benzene group to carbon, respectively. The dihedral angle between the two phenyl rings is 72.13 (7) degrees . Inter molecular O-H?N, O-H?F, C-H?F, C-H?O and C-H?N hydrogen bonds are found in the crystal structure. PMID- 22091005 TI - N-Benzoyl-N-(3-methyl-phen-yl)-O-[2-(2-nitro-phen-yl)acet-yl]hydroxyl-amine. AB - In the title mol-ecule, C(22)H(18)N(2)O(5), the nitro-substituted ring makes a dihedral angle of 81.9 (1) degrees with the benzoyl ring and a dihedral angle of 12.1 (1) degrees with the methyl-substituted ring. PMID- 22091006 TI - Ethyl 2-[(carbamothioyl-amino)-imino]-propano-ate. AB - The title compound, C(6)H(11)N(3)O(2)S, consists of a roughly planar mol-ecule (r.m.s deviation from planarity = 0.077 A for the non-H atoms) and has the S atom in an anti position to the imine N atom. This N atom is the acceptor of a strongly bent inter-nal N-H?N hydrogen bond donated by the amino group. In the crystal, mol-ecules are arranged in undulating layers parallel to (010). The mol ecules are linked via inter-molecular amino-carboxyl N-H?O hydrogen bonds, forming chains parallel to [001]. The chains are cross-linked by N(carbazone)-H?S and C-H?S inter-actions, forming infinite sheets. PMID- 22091007 TI - 5-Methyl-1,2,3,3a-tetra-hydro-benzo[e]pyrrolo-[2,1-b][1,3]oxazepin-10(5H)-one. AB - The asymmetric unit of the title compound, C(13)H(15)NO(2), the main product of a photoreaction, contains two crystallographically independent mol-ecules. In both mol-ecules, the conformation of the seven-membered ring is twist sofa and that of the five-membered rings is envelope. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds. PMID- 22091008 TI - N-(2,4-Dinitro-phen-yl)-1,3-dimeth-oxy-isoindolin-2-amine. AB - In the title compound, C(16)H(16)N(4)O(6), the planes of the isoindole and dinitro-benzene groups make a dihedral angle between of 84.15 (8) degrees . The N atom of the isoindole group is displaced by 0.2937 (3) A from the plane through the remaining atoms. An intra-molecular N-H?O inter-action occurs. In the crystal, inversion dimers linked by pairs of N-H?O hydrogen bonds occur. PMID- 22091009 TI - Bis(dimethyl-ammonium) 2,2'-(1,3,6,8-tetra-oxo-2,7-diaza-pyrene-2,7-di yl)diacetate. AB - The asymmetric unit of title compound, 2C(2)H(8)N(+).C(18)H(8)N(2)O(8) (2-), comprises one crystallographically independent dimethyl-ammonium cation and half of a 2,2'-(1,3,6,8-tetra-oxo-2,7-diaza-pyrene-2,7-di-yl)diacetate dianion. The anion lies on an inversion centre and the two carboxyl-ate groups are in trans positions based on the naphthaleneteracarb-oxy-lic diimide group. The crystal packing is stabilized by N-H?O hydrogen bonds between cations and anions, as well as by pi-pi inter-actions between the naph-thaleneteracarb-oxy-lic diimide groups [centroid-centroid distance = 4.812 (3) A]. PMID- 22091010 TI - 2-Amino-6-(pyrrolidin-1-yl)-4-p-tolyl-pyridine-3,5-dicarbonitrile. AB - In the title compound, C(18)H(17)N(5), the pyrrolidine ring adopts an envelope conformation. The pyrrolidine ring is disordered over two sets of sites with occupancy factors of 0.648 (6) and 0.352 (6). The dihedral angles between the pyrrolidine and pyridine rings are 14.6 (3) degrees for the major component and 16.2 (6) degrees for the ninor component. The crystal structure is stabilized by inter-molecular N-H?N and C-H?N inter-actions. PMID- 22091011 TI - 3-(2-Meth-oxy-naphthalen-1-yl)-2-benzofuran-1(3H)-one. AB - The asymmetric unit of the title compound, C(19)H(14)O(3), contains two crystallographically independent mol-ecules in which the dihedral angles between the naphthalene and benzofuran ring systems are 76.49 (7) and 86.17 (7) degrees . In the crystal, mol-ecules are linked by inter-molecular C-H?O hydrogen-bonding inter-actions into chains running parallel to the a axis. In addition, the crystal packing is stabilized by C-H?pi inter-actions. PMID- 22091012 TI - exo-4-[(1H-Benzimidazol-2-yl)meth-yl]-10-oxa-4-aza-tricyclo-[5.2.1.0]decane-3,5 dione. AB - In the title compound, C(16)H(15)N(3)O(3), the dihedral angle between the approximately planar benzimidazolyl group (r.m.s. deviation = 0.010 A) and the pyrrolidine ring is 78.20 (6) degrees . The C-C-N bond angle of the bridging CH(2) group is 112.14 (16) degrees . In the crystal, mol-ecules are linked via N H?N hydrogen bonds, forming infinite chains parallel to [101] and [10[Formula: see text]]. PMID- 22091013 TI - 3,5-Bis(4-meth-oxy-phen-yl)-4,5-dihydro-isoxazole. AB - In the title compound, C(17)H(17)NO(3), the five-membered isoxazoline ring adopts an envelope conformation with the chiral C atom at the flap position and 0.133 (2) A out of the mean plane formed by the other four atoms. The two benzene rings form dihedral angles of 6.05 (5) and 81.52 (5) degrees with the C-C-N-O plane of the isoxazoline ring. The crystal structure is stabilized by weak C-H?O hydrogen bonds and C-H?pi inter-actions. PMID- 22091014 TI - N-(3-Chloro-phen-yl)succinimide. AB - In the title compound, C(10)H(8)ClNO(2), the chloro-benzene and the essentially planar (r.m.s. deviation = 0.030 A) pyrrolidine ring are tilted by 59.5 (1) degrees with respect to one another. PMID- 22091015 TI - 2-(5-Fluoro-7-methyl-3-methyl-sulfanyl-1-benzofuran-2-yl)acetic acid. AB - The title compound, C(12)H(11)FO(3)S, was prepared by alkaline hydrolysis of ethyl 2-(5-fluoro-7-methyl-3-methyl-sulfanyl-1-benzofuran-2-yl)acetate. In the crystal, the carboxyl groups are involved in inter-molecular O-H?O hydrogen bonds, which link the mol-ecules into centrosymmetric dimers. PMID- 22091016 TI - N-(2-Hy-droxy-benz-yl)adamantan-1-aminium bromide. AB - There are two independent ion pairs in the asymmetric unit of the title compound, C(17)H(24)NO(+).Br(-). In the crystal, the ions are linked by inter-molecular N H?Br and O-H?Br hydrogen bonds. PMID- 22091017 TI - Diethyl [(9-anthr-yl)(4-methyl-anilino)meth-yl]phospho-nate. AB - The title compound, C(26)H(28)NO(3)P, crystallized with two independent mol ecules in the asymmetric unit. The structural features (bond lengths and angles) of the two mol-ecules are almost identical. The inter-planar angle between the anthracene and toluidine rings is similar in the two mol-ecules, with values of 82.92 (5) and 80.70 (5) degrees . In the crystal, both molecules form inversion dimers linked by pairs of N-H?O hydrogen bonds. Three of the four ethyl groups are disordered over two sets of sites, the major components having occupancies of 0.748 (15), 0.77 (4) and 0.518 (19). PMID- 22091018 TI - 2-(Pyridin-2-yl-amino)-pyridinium thio-cyanate acetonitrile monosolvate. AB - The title compound, C(10)H(10)N(3) (+).NCS(-).CH(3)CN, is the acetonitrile solvate of the thio-cyanate salt of protonated dipyridin-2-yl-amine. Protonation occurs at one of the pyridine N atoms. The mol-ecular geometry around the central N atom is essentially planar (sum of angles = 359.89 degrees ). In the crystal, N H?N hydrogen bonds, as well as C-H?S contacts link the different residues into chains along the c-axis direction. Inter-action between aromatic systems gives rise to pi-stacking, the shortest distance between two pi-systems being 3.6902 (6) A. Both the protonated and the non-protonated pyridyl groups are involved in the latter inter-action. PMID- 22091019 TI - 2-[(E)-4-(Dimethyl-amino)-benzyl-idene]indan-1-one. AB - In the title compound, C(18)H(17)NO, the dihydro-indene ring system is approximately planar, with a maximum deviation of 0.041 (2) A. This ring system is almost coplanar with the benzene ring, making a dihedral angle of 5.22 (9) degrees . In the crystal, inter-molecular C-H?O hydrogen bonds link the mol ecules into chains along the b axis. PMID- 22091020 TI - (1S*,3S*,8S*,10S*)-10-Fluoro-15-oxa-tetra-cyclo-[6.6.1.0.0]penta-deca-5,12-dien-3 ol. AB - The title compound, C(14)H(17)FO(2), was obtained from anti-4a,9a:8a,10a-diep-oxy 1,4,4a,5,8,8a,9,9a,10,10a-deca-hydro-anthra-cene via tandem hydrogen-fluoride mediated epoxide ring-opening and transannular oxacyclization. With the two cyclo hexene rings folded towards the oxygen bridge, the title tetra-cyclic fluoro alcohol mol-ecule displays a conformation remin-iscent of a pagoda. The crystal packing is effected via inter-molecular O-H?O hydrogen bonds, which link the mol ecules into a zigzag chain along the b axis. PMID- 22091021 TI - 1,3-Diallyl-6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one. AB - In the mol-ecule of the title compound, C(12)H(12)BrN(3)O, the fused-ring system is essentially planar, the largest deviation from the mean plane being 0.0148 (3) A. The two allyl groups are nearly perpendicular to the imidazo[4,5-b]pyridine plane [C-C-N-C torsion angles of 81.6 (4) and -77.2 (4) degrees ] and point in the same direction. The planes through the atoms forming each allyl group are nearly perpendicular to the imidazo[4,5-b]pyridin-2-one system, as indicated by the dihedral angles between them of 80.8 (5) and 73.6 (5) degrees . PMID- 22091022 TI - 1,1-Dibenzyl-3-(4-fluoro-benzo-yl)thio-urea. AB - In the title compound, C(22)H(19)FN(2)OS, the 2-fluoro-benzoyl group adopts a trans conformation with respect to the thiono S atom across the N-C bond. In the crystal, inter-molecular N-H?S, C-H?S and C-H?O hydrogen bonds link the mol ecules, forming a two-dimensional network parallel to (101). PMID- 22091023 TI - (9S,13R,14S)-7,8-Didehydro-4-(4-fluoro-benz-yloxy)-3,7-dimeth-oxy-17-methyl morphinan-6-one sesquihydrate. AB - In the title sinomenine derivative, C(26)H(28)FNO(4).1.5H(2)O, the dihedral angle between the two aromatic rings is 55.32 (6) degrees . The N-containing ring has an approximate chair conformation, while other two rings have approximate envelope and half-chair conformations. One water mol-ecule is located on a twofold symmetry axis. In the crystal, the water mol-ecules form O-H?O and O-H?N hydrogen bonds, bridging symmetry-related main mol-ecules. PMID- 22091024 TI - Methyl 3-(4-isopropyl-phen-yl)-1-phenyl-3,3a,4,9b-tetra-hydro-1H-chromeno[4,3 c]isoxazole-3a-carboxyl-ate. AB - In the title compound, C(27)H(27)NO(4), the five-membered isoxazole ring adopts an envelope conformation and the six-membered pyran ring adopts a half-chair conformation. The dihedral angle between the mean planes of the isoxazole ring and the chromene ring system is 54.95 (4) degrees . PMID- 22091025 TI - Methyl 6-(4-chloro-phen-yl)-2,4-dimethyl-1,3-dioxo-1,2,3,4,6,6a,7,12b-octa-hydro chromeno[4',3':4,5]pyrano[2,3-d]pyrimidine-6a-carboxyl-ate. AB - In the title compound, C(24)H(21)ClN(2)O(6), the two fused six-membered pyran rings adopt half-chair conformations. The dihedral angle between the pyrimidine ring and the chloro-phenyl ring is 51.55 (3) degrees . In the crystal, mol-ecules are linked by pairs of weak inter-molecular C-H?O hydrogen bonds, forming inversion dimers. A C-H?pi inter-action is also observed. PMID- 22091026 TI - Tetra-ethyl-ammonium bicarbonate trihydrate. AB - In the title compound, C(8)H(20)N(+).CHO(3) (-).3H(2)O, the bicarbon-ate anion, which has a small mean deviation from the plane of 0.0014 A, fully utilises its three O and one H atom to form various O-H?O hydrogen bonds with the three water mol-ecules in the asymmetric unit, generating a hydrogen-bonded layer, which extends along (10[Formula: see text]). The tetra-ethyl-ammonium cations, as the guest species, are accommodated between every two neighboring layers, constructing a sandwich-like structure with an inter-layer distance of 7.28 A. PMID- 22091027 TI - 2,2-Diphenyl-acetamide. AB - In the title compound, C(14)H(13)NO, which has two mol-ecules in the asymmetric unit, the dihedral angles between the mean planes of the benzene rings are 84.6 (7) and 85.0 (6) degrees . N-H?O hydrogen bonds [forming R(2) (2)(8) ring motifs] and C-H?O hydrogen bonds dominate the crystal packing, forming zigzag chains parallel to the a axis. In addition, weak inter-molecular C-H?pi inter-actions are observed. PMID- 22091028 TI - Methyl 2-(4-hy-droxy-benzo-yl)benzoate. AB - In the title compound, C(15)H(12)O(4), the dihedral angle between the benzene rings is 64.0 (6) degrees . In the crystal, mol-ecules are linked by O-H?O hydrogen bonds, forming C(8) chains propagating in [10[Formula: see text]] and the packing is reinforced by weak C-H?O inter-actions. PMID- 22091029 TI - 2-Phenyl-naphtho-[1,8-de][1,3,2]diaza-borinane. AB - The title compound, C(16)H(13)BN(2), is one compound in a series of diaza borinanes featuring substitution at the 1, 2 and 3 positions in the nitro-gen boron heterocycle. The title compound is slightly distorted from planarity, with a dihedral angle of 9.0 (5) degrees between the mean planes of the naphthalene system and the benzene ring. The m-carbon atom of the benzene ring exhibits the greatest deviation of 0.164 (2) A from the 19-atom mean plane defined by all non H atoms. The two N-B-C-C torsion angles are 6.0 (3) and 5.6 (3) degrees . In the crystal, mol-ecules are linked by pi-pi inter-actions into columns, with a distance of 3.92 (3) A between the naphthalene ring centroids. Adjacent pi stacked columns, co-linear with the b-axis, are linked by C-H?pi inter-actions. PMID- 22091030 TI - 3,4-Dihy-droxy-phenethyl acetate. AB - In the title compound, C(10)H(12)O(4), the dihedral angle between the acetate group and the aromatic ring is 20.47 (10) degrees . In the crystal, mol-ecules are linked by O-H?O hydrogen bonds, forming [001] chains. Weak C-H?O inter actions consolidate the packing. PMID- 22091031 TI - 2,4,6-Trimethyl-anilinium chloro-acetate. AB - In the crystal structure of the title compound, C(9)H(14)N(+).C(2)H(2)ClO(2) (-), inter-molecular N-H?O inter-actions link the mol-ecules into a one-dimensional linear structure. PMID- 22091032 TI - 3-Allyl-6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one. AB - In the mol-ecule of the title compound, C(9)H(8)BrN(3)O, the fused-ring system is almost planar, the largest deviation from the mean plane being 0.008 (3) A. The plane through the atoms forming the allyl group is roughly perpendicular to the imidazo[4,5-b]pyridin-2-one system, as indicated by the dihedral angle between them of 70.28 (11) degrees . In the crystal, each mol-ecule is linked to its symmetry equivalent about the center of inversion by a pair of strong N-H?O hydrogen bond, forming inversion dimers. PMID- 22091033 TI - (E)-4-Chloro-N-(2,4,6-trimethyl-benzyl-idene)aniline. AB - In the title compound, C(16)H(16)ClN, the dihedral angle between the benzene rings is 24.61 (13) degrees . In the crystal, only van der Waals inter-actions occur between neighbouring mol-ecules. PMID- 22091034 TI - (E)-2-(2-Formyl-phen-oxy-meth-yl)-3-phenyl-prop-2-ene-nitrile. AB - In the title compound, C(17)H(13)NO(2), the dihedral angle between the benzene and the phenyl ring is 65.92 (7) degrees . The carbonitrile side chain is almost linear, the C-C-N angle being 175.55 (14) degrees . The crystal structure is stabilized by inter-molecular C-H?O inter-actions. PMID- 22091035 TI - 2-Cyano-N'-(2-hy-droxy-3-meth-oxy-benzyl-idene)acetohydrazide. AB - The title compound, C(11)H(11)N(3)O(3), was obtained by the reaction of 3-meth oxy-salicyl-aldehyde with cyano-acetohydrazide in methanol. There is an intra molecular O-H?N hydrogen bond in the mol-ecule. In the crystal, mol-ecules are linked by N-H?O hydrogen bonds, generating chains running along the b axis. PMID- 22091036 TI - 2-Cyano-N'-(5-hy-droxy-2-nitro-benzyl-idene)acetohydrazide monohydrate. AB - The title compound, C(10)H(8)N(4)O(4).H(2)O, was obtained by the reaction of 5-hy droxy-2-nitro-benzaldehyde with cyano-acetohydrazide in methanol. The non-H atoms of the hydrazone molecule are approximately coplanar, with a mean deviation from the least-squares plane of 0.056 A. In the crystal, mol-ecules are linked by N H?O, O-H?N and O-H?O hydrogen bonds, generating a three-dimensional network. PMID- 22091037 TI - 6-Nitro-2,3-dihydro-1H-pyrrolo-[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione. AB - In the two mol-ecules of the asymmetric unit of the title compound, C(12)H(11)N(3)O(4), the seven-membered diazepine ring adopts a boat conformation (with the two phenyl-ene C atoms representing the stern and the methine C atom the prow). The five-membered pyrrole ring, which has an envelope conformation, makes dihedral angles of 60.47 (10) and 54.69 (9) degrees with the benzene ring of the benzodiazepine unit in the two mol-ecules. In the crystal, inter-molecular N-H?O hydrogen bonds and pi-pi stacking inter-actions [centroid-centroid distance = 3.8023 (7)-3.8946 (7) A] lead to the formation of a three-dimensional framework. PMID- 22091038 TI - 2-Ethyl-N-[(5-nitro-thio-phen-2-yl)methyl-idene]aniline. AB - In the title compound, C(13)H(12)N(2)O(2)S, the dihedral angle between the benzene and thio-phene rings is 36.72 (8) degrees . An inter-molecular C-H?pi inter-action contributes to the stability of the crystal structure. PMID- 22091039 TI - Meth-yl(phen-yl)phosphinic acid. AB - The crystal structure of the title compound, C(7)H(9)O(2)P, displays O-H?O hydrogen bonding , which links individual mol-ecules related via the c-glide plane and translational symmetry along the crystallographic b-axis direction into continuous chains. PMID- 22091040 TI - Ethyl [(benzyl-aza-nium-yl)(2-hy-droxy-phen-yl)meth-yl]phospho-nate. AB - The title compound, C(16)H(20)NO(4)P, crystallizes as a zwitterion. In the mol ecule, the two aromatic rings form a dihedral angle of 55.2 (1) degrees . In the crystal, inter-molecular N-H?O and O-H?O hydrogen bonds link the mol-ecules into columns propagating in [010]. PMID- 22091041 TI - 2-[2-(4-Meth-oxy-phen-yl)-2-oxoeth-yl]malononitrile. AB - The title compound, C(12)H(10)N(2)O(2), was obtained unintentionally during the synthesis of 2-amino-5-(4-meth-oxy-phen-yl)furan-3-carbonitrile. In the crystal, weak inter-mol-ecular C-H?N and C-H?pi inter-actions link the mol-ecules into columns propagating in [010]. PMID- 22091042 TI - Morpholin-4-ium morpholine-4-carbo-dithio-ate. AB - The title compound, C(4)H(10)NO(+).C(5)H(8)NOS(2) (-), is built up of a morpholinium cation and a dithio-carbamate anion. In the crystal, two structurally independent formula units are linked via N-H?S hydrogen bonds, forming an inversion dimer, with graph-set motif R(4) (4)(12). PMID- 22091043 TI - 1,4-Dibromo-naphthalene-2,3-diol. AB - In the title compound (r.m.s. deviation for the non-H atoms = 0.020 A), C(10)H(6)Br(2)O(2), an intra-molecular O-H?O hydrogen bond generates an S(6) ring. In the crystal, the same H atom also forms an inter-molecular O-H?O hydrogen bond, generating a C(2) chain propagating in [100]. The other O-H hydrogen forms a weak O-H?pi inter-action, and short Br?Br contacts [3.5972 (9) A] also occur. PMID- 22091044 TI - 1-(2-Naphth-yl)-3-phenyl-3-(4,5,6,7-tetra-hydro-1,2,3-benzoselenadiazol-4 yl)propan-1-one. AB - In the title compound, C(25)H(22)N(2)OSe, the fused six-membered cyclo-hexene ring of the 4,5,6,7-tetra-hydro-1,2,3-benzoselenadiazole group adopts a near half chair conformation and the five-membered 1,2,3-selenadiazole ring is essentially planar (r.m.s. deviation = 0.004 A). There are weak inter-molecular C-H?O and C H?pi inter-actions in the crystal structure. Inter-molecular pi-pi stacking is also observed between the naphthyl units, with a centroid-centroid distance of 3.529 (15) A. PMID- 22091045 TI - 1,5-Anhydro-2-de-oxy-1,2-C-dichloro-methyl-ene-3,4,6-tri-O-(4-meth-oxy-benz-yl)-d glycero-d-gulo-hexitol. AB - The pyranosyl ring in the title compound, C(31)H(34)Cl(2)O(7), adopts a twist boat conformation. The 4-meth-oxy-benzyl groups are located in equatorial positions with the meth-oxy groups nearly coplanar with their respective rings [dihedral angles of 0.2 (3) and 9.4 (2) degrees ]. The aromatic rings adopt orientations enabling them to participate in C-H?pi inter-actions with neighboring meth-oxy groups. The crystal structure is additionally stabilized by weak C-H?O inter-actions. PMID- 22091046 TI - 1,1,2,2-Tetra-kis(1,3-benzoxazol-2-yl)ethene. AB - The title compound, C(30)H(16)N(4)O(4), reveals [Formula: see text] crystallographic and mol-ecular symmetry and accordingly the asymmetric unit comprises one half-mol-ecule. The dihedral angle between the planes of the two geminal benzoxazole rings is 74.39 (5) degrees . The packing features weak C-H?N and pi-pi inter-actions [centroid-centroid distance = 3.652 (1) A]. PMID- 22091047 TI - 3-Methyl-4-{[(3-{[(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl idene)(phen-yl)meth-yl]amino-meth-yl}benz-yl)amino](phen-yl)methyl-idene}-1 phenyl-1H-pyrazol-5(4H)-one. AB - The complete mol-ecule of the title compound, C(42)H(36)N(6)O(2), is generated by a crystallographic twofold axis with two C atoms of the central phenyl group lying on the axis. In the independent part of the mol-ecule, one amino group is involved in an intra-molecular N-H?O hydrogen bond, and the two adjacent phenyl rings are twisted from the plane of the pyrazolone ring with dihedral angles of 6.82 (3) and 88.32 (6) degrees . The crystal packing exhibits no classical inter molecular contacts. PMID- 22091048 TI - 5'-Methyl-sulfanyl-4'-oxo-7'-phenyl-3',4'-dihydro-1'H-spiro-[cyclo-hexane-1,2' quinazoline]-8'-carbonitrile dimethyl-formamide monosolvate. AB - In the title compound, C(21)H(21)N(3)OS.C(3)H(7)NO, the carbonitrile mol-ecule is built up of two fused six-membered rings and one six-membered ring linked through a spiro C atom. The 1,3-diaza ring adopts an envelope conformation and the cyclo hexane ring adopts a chair conformation. The dihedral angle between the aromatic rings is 46.7 (3) degrees . In the crystal, the components are linked by N-H?O hydrogen bonds. PMID- 22091049 TI - 1-(2-Hy-droxy-eth-yl)-4-{3-[(E)-2-(trifluoro-meth-yl)-9H-thioxanthen-9-yl idene]prop-yl}piperazine-1,4-diium bis-(3-carb-oxy-prop-2-enoate). AB - In the title salt, C(23)H(27)F(3)N(2)OS(+).2C(4)H(3)O(4) (-), a non-merohedral twin [ratio of the twin components = 0.402 (1):0.598 (1)], the -CF(3) group is disordered over two sets of sites with occupancy factors in the ratio 0.873 (2):0.127 (2). The dihedral angle between the two outer aromatic rings of the 9H thioxanthene unit, whose thio-pyran ring has a screw-boat conformation, is 33.01 (9) degrees . The diprotonated piperazine ring adopts a chair conformation. In the crystal, inter-molecular O-H?O, N-H?O and C-H?O hydrogen bonds between neighboring mol-ecules form zigzag chains along the a axis and contribute to the stabilization of the packing. PMID- 22091050 TI - 2-Chloro-N-(3,4-dimethyl-phen-yl)benzamide. AB - In the title compound, C(15)H(14)ClNO, the conformation of the N-H bond is anti to the meta-methyl group in the aniline ring, while that of the C=O bond is anti to the ortho-chloro group in the benzoyl ring. The mean planes through the two benzene rings make a dihedral angle of 80.8 (2) degrees . In the crystal, mol ecules are linked by inter-molecular N-H?O hydrogen bonds, forming column-like chains along the b axis. PMID- 22091051 TI - 2,2-Dichloro-1-(3,3,6-trimethyl-9-oxo-1,5-diaza-bicyclo-[4.3.0]nonan-5 yl)ethanone. AB - In the title mol-ecule, C(12)H(18)Cl(2)N(2)O(2), the six-membered ring is in a chair conformation and the five-membered ring is in an envelope conformation. In the crystal, weak inter-molecular bifurcated (C-H)(2)?O hydrogen bonds connect mol-ecules into chains along [010]. PMID- 22091052 TI - 4-(1H-Benzimidazol-2-ylmeth-oxy)-3-meth-oxy-benzaldehyde tetra-hydrate. AB - In the title compound, C(16)H(14)N(2)O(3).4H(2)O, the dihedral angle between the mean planes of the benzimidazole ring system and benzene ring is 2.9 (1) degrees . The aldehyde group is disordered over two sets of sites with refined occupancies of 0.559 (4) and 0.441 (4). In the crystal, extensive inter-molecular O-H?O, O-H?N and N-H?O hydrogen bonds in concert with weak pi-pi stacking inter actions [centroid-centroid distances = 3.6104 (9), 3.6288 (9) and 3.9167 (10) A] create a three-dimensional network. PMID- 22091053 TI - (E)-Methyl N'-(2,4,5-trimeth-oxy-benzyl-idene)hydrazinecarboxyl-ate. AB - The title mol-ecule, C(12)H(16)N(2)O(5), adopts a trans configuration with respect to the C=N bond. In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into chains in [001], and weak inter-molecular C-H?O inter actions further link the chains into corrugated layers parallel to the bc plane. PMID- 22091054 TI - 4-[3-(Benzyl-amino)-2-hy-droxy-prop-yl]-2,6-di-tert-butyl-phenol. AB - In the title compound, C(24)H(35)NO(2), the planes of the two aromatic rings form a dihedral angle of 72.76 (4) degrees . In the crystal, mol-ecules are linked by O-H?O and O-H?N hydrogen-bond inter-actions, forming an extended two-dimensional framework parallel to the ab plane. PMID- 22091055 TI - A second monoclinic polymorph of 6-amino-1,3-dimethyl-5-[(E)-2-(methyl-sulfan yl)benzyl-idene-amino]-pyrimidine-2,4(1H,3H)-dione. AB - A new monoclinic form of the title compound, C(14)H(16)N(4)O(2)S, has been identified unexpectedly during an attempt to synthesize a coordination compound. The heterocyclic ring is essentially planar (r.m.s. deviation = 0.005 A) and makes a dihedral angle of 8.77 (5) degrees with the benzene ring. This is in contrast to 12.24 (7) degrees reported for the first monoclinic polymorph [Booysen et al. (2011 ?). Acta Cryst. E67, o1592]. An intra-molecular N-H?S hydrogen bond is observed. In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into zigzag chains along the b axis. The closest distance between the centroids of symmetry-related heterocyclic rings is 3.5161 (6) A. PMID- 22091056 TI - (Z)-2-(4-tert-Butyl-phen-yl)-1-(4-chloro-1-ethyl-3-methyl-1H-pyrazol-5-yl)-2 cyano-vinyl pivalate. AB - In the title compound, C(24)H(30)ClN(3)O(2), the dihedral angle between the benzene and pyrazole rings is 56.86 (7) degrees . The C=C bond is significantly twisted, as indicated by the dihedral angle of 12.26 (1) degrees between the two sets of three atoms linked by the double bond. PMID- 22091057 TI - 3,3'-(Ethane-1,2-di-yl)bis-(6-methyl-3,4-dihydro-2H-1,3-benzoxazine). AB - The asymmetric unit of the title compound, C(20)H(24)N(2)O(2), contains one half mol-ecule, which is completed by inversion symmetry. In the crystal, mol-ecular chains are formed through non-classical C-H?O hydrogen bonds, formed between axial H atoms of the oxazine ring and a O atom of a neighboring mol-ecule. PMID- 22091058 TI - 4-(4-{[(2-Phenyl-quinazolin-4-yl)-oxy]methyl}-1H-1,2,3-triazol-1-yl)butan-1-ol hemihydrate. AB - The title compound, C(21)H(21)N(5)O(2).0.5H(2)O, has two fused six-membered rings linked to a benzene ring and to a triazole ring, which is connected to a butanol group. The quinazoline ring forms a dihedral angle of 7.88 (8) degrees with the benzene ring, while the triazole ring is approximately perpendicular to the benzene ring and to the quinazoline system, making dihedral angles of 84.38 (10) and 76.55 (8) degrees , respectively. The stereochemical arrangement of the butanol chain, with a C-C-C-C torsion angle of 178.34 (19) degrees , corresponds to an anti-periplanar conformation. However the position of the -OH group is split into two very close [O-O = 0.810(3) A] positions of equal occupancy. The crystal structure features O-H?N and O-H?O hydrogen bonds, building an infinite three-dimensional network. The water molecule is located on a half-filled general position. PMID- 22091059 TI - 1-(2-Ureidoeth-yl)quinolinium tetra-phenyl-borate. AB - In the cation of the title salt, C(12)H(14)N(3)O(+).C(24)H(20)B(-), the dihedral angle between the quinoline ring and the mean plane of the urea fragment is 61.51 (5) degrees . In the crystal, the cations inter-act through weak C-H?O hydrogen bonding, forming a zigzag chain along the c-axis direction; the cations and anions are involved in weak inter-molecular C-H?pi and N-H?pi inter-actions as donors and acceptors, respectively. PMID- 22091060 TI - N-(2-Amino-3,5-dibromo-benz-yl)-N-methyl-cyclo-hexan-1-aminium p toluenesulfonate. AB - The title compound, C(14)H(21)Br(2)N(2) (+).C(7)H(7)O(3)S(-), features a salt of protonated bromhexine, a pharmaceutical used in the treatment of respiratory disorders, and the p-toluenesulfonate anion. The crystal packing is stabilized by inter-molecular N-H?O, N-H?Br and C-H?O hydrogen bonds. PMID- 22091061 TI - 4,4'-Bipyridine-pyridine-3,5-dicarb-oxy-lic acid (3/4). AB - In the title compound, 3C(10)H(8)N(2).4C(7)H(5)NO(4), the asymmetric unit contains two mol-ecules of pyridine-3,5-dicarb-oxy-lic acid and one mol-ecule of 4,4'-bipyridine in general positions together with one mol-ecule of 4,4' bipyridine lying across a centre of inversion, thus giving a 4:3 molar ratio of pyridine-3,5-dicarb-oxy-lic acid to 4,4'-bipyridine. The dihedral angle between the bipyridine rings on general positions is 21.2 (2) degrees . These mol-ecular units are linked by O-H?N hydrogen bonds forming an extended two-dimensional framework in the crystal. PMID- 22091062 TI - 1-Phenyl-isatin. AB - In the title compound, C(14)H(9)NO(2), the phenyl ring makes a dihedral angle of 50.59 (5) degrees with the mean plane of the isatin fragment. In the crystal, mol-ecules are linked through weak inter-molecular C-H?O hydrogen bonds. The crystal structure also exhibits two slipped pi-pi inter-actions between the benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.968 (3) A, inter-planar distance = 3.484 (3) A and slippage = 1.899 (3) A], and between the phenyl rings of neighbouring mol-ecules [centroid-centroid distance = 3.968 (3) A, inter-planar distance = 3.638 (3) A and slippage = 1.584 (3) A]. PMID- 22091063 TI - (8aRS)-8,8a-Dihydro-furo[3,2-f]indolizine-6,9(4H,7H)-dione. AB - The title compound, C(10)H(9)NO(3), is a chiral mol-ecule with one stereogenic carbon atom, but which crystallizes as a racemate in the centrosymmetric space group P2(1)/n. The central six-membered ring of the indolizine moiety adopts a definite envelope conformation, while the conformation of the oxopyrrolidine ring is close to that of a flat-envelope with a maximum deviation of 0.352 (1) A for the flap atom. PMID- 22091064 TI - 1-(4-Fluoro-phen-yl)-2-(1H-imidazol-1-yl)ethanone. AB - In the title compound, C(11)H(9)FN(2)O, the dihedral angle between the rings is 87.50 (4) degrees . In the crystal, inter-molecular C-H?N hydrogen bonds link the mol-ecules in a stacked arrangement along the c axis. PMID- 22091065 TI - 5-(Pyridin-2-yl)-3,3'-bi(1H-1,2,4-triazole). AB - In the title mol-ecule, C(9)H(7)N(7), the two triazole rings are twisted by an angle of 3.8 (5) degrees ; the central triazole ring is twisted by 32.3 (6) degrees with respect to the pyridyl ring. The crystal packing consists of layers generated by inter-molecular N-H?N hydrogen bonds. PMID- 22091066 TI - 4-Hydrazinyl-idene-1-methyl-3H-2lambda,1-benzothia-zine-2,2-dione. AB - In the title compound, C(9)H(11)N(3)O(2)S, the thia-zine ring adopts a half-chair conformation. In the crystal structure N-H?N hydrogen bonds connect two mol ecules into a centrosymmetric dimer, forming an R(2) (2)(6) ring motif. These dimers are further connected into chains by N-H?O and C-H?O hydrogen bonds. PMID- 22091067 TI - 3-Hy-droxy-pyridinium-2-carboxylate. AB - Comparable to many amino acids, the title compound, C(6)H(5)NO(3), is a substitution product of picolinic acid. The mol-ecule shows approximate non crystallographic C(s) symmetry. Like many amino acids, the mol-ecule is present in its zwitterionic state. Intra- as well as inter-molecular hydrogen bonds are observed, the latter connecting the mol-ecules into zigzag chains along the crystallographic b axis. An inter-molecular C-C distance of only 3.368 (2) A exclusively involving carbon atoms of aromatic rings (centroid-centroid separation = 3.803 A) is indicative of pi-pi inter-actions connecting the mol ecules into stacks along the crystallographic a axis. PMID- 22091068 TI - 7-Meth-oxy-1-(4-nitro-benzo-yl)naph-thalen-2-yl 4-nitro-benzoate. AB - In the title compound, C(25)H(16)N(2)O(8), the dihedral angle between the naphthalene ring system and the benzene ring of the nitro-phenyl ketone unit is 82.64 (7) degrees . The bridging ester O-C(=O)-C plane makes dihedral angles of 42.12 (8) and 11.47 (9) degrees , respectively, with the naphthalene ring system and the benzene ring of the nitro-phenyl ester unit. In the crystal, two types of weak inter-molecular C-H?O inter-actions are observed. PMID- 22091069 TI - N,N-Bis(diphenyl-phosphan-yl)cyclo-butanamine. AB - In the title compound, C(28)H(27)NP(2), the N atom adopts an almost planar geometry with the two P atoms and the C atom attached to it, with a distance of 0.066 (2) A between the N atom and the C/P/P plane. The distorted trigonal pyramidal geometry of the N atom is further illustrated by bond angles ranging between 115.22 (11) and 123.53 (8) degrees . Bond angles varying from 99.99 (9) to 108.07 (9) degrees are indicative of the distorted pyramidal environment around the P atoms. An intra-molecular C-H?P hydrogen bond occurs. In the crystal, inter-molecular C-H?pi inter-actions link the mol-ecules into a supra molecular network. PMID- 22091070 TI - N-(5-Bromo-pyridin-2-yl)acetamide. AB - The asymmetric unit of the title compound, C(7)H(7)BrN(2)O, contains two mol ecules, in one of which the methyl H atoms are disorderd over two orientations in a 0.57 (3):0.43 (3) ratio. The dihedral angles between the pyridine rings and the acetamide groups are 7.27 (11) and 8.46 (11) degrees . In the crystal, mol-ecules are linked by N-H?O and C-H?O hydrogen bonds generating bifurcated R(2) (1)(5) ring motifs, which in turn lead to [110] chains. PMID- 22091071 TI - 2-Amino-6-nitro-1,3-benzothia-zol-3-ium hydrogen sulfate. AB - In the title molecular salt, C(7)H(6)N(3)O(2)S(+).HSO(4) (-), the 2-amino-6-nitro 1,3-benzothia-zole ring system is essentially planar [mean deviation = 0.0605 (4) A]. In the crystal, N-H?O and O-H?O hydrogen-bonding inter-actions result in a layer motif. PMID- 22091072 TI - rac-Dimethyl [(9-anthr-yl)(4-methyl-anilino)meth-yl]phospho-nate. AB - The title compound, C(24)H(24)NO(3)P, crystallizes as a racemate with two mol ecules in the asymmetric unit. The structural features (bond lengths and angles) of the two mol-ecules are almost identical. The dihedral angle between the anthracene and toluidine rings is similar in the two mol-ecules, with values of 48.36 (9) and 51.15 (9) degrees . The methyl groups of one of the meth-oxy groups in one mol-ecule is disordered over two sets of sites, the major component having a site occupancy of 0.636 (3). In the crystal, both molecules are linked into inversion dimers by pairs of N-H?O hydrogen bonds. PMID- 22091073 TI - N,N'-Bis(2-chloro-benz-yl)-N''-(2,2,2-trichloro-acet-yl)phospho-ric triamide. AB - The P atom in the title compound, C(16)H(15)Cl(5)N(3)O(2)P, exhibits a tetra hedral coordination geometry and the phosphoryl and carbonyl groups are anti with respect to one another. The dihedral angle between the benzene rings is 44.90 (15) degrees . One of the 2-chloro-benzyl-amido fragments is disordered over two sets of sites with occupancies of 0.8823 (17) and 0.1177 (17). In the crystal, adjacent mol-ecules are linked via N-H?O(P) and N-H?O(C) hydrogen bonds into an extended chain running parallel to the a axis. PMID- 22091074 TI - 2-Phenyl-imidazolium hemi(benzene-1,3-dicarboxyl-ate) monohydrate. AB - The asymmetric unit of the title compound, C(9)H(9)N(2) (+).0.5C(8)H(4)O(4) ( ).H(2)O, contains one 2-phenyl-imidazolium cation, half a benzene-1,3-dicarboxyl ate anion and one water mol-ecule. In the crystal, components are connected by N H?O and O-H?O hydrogen-bonding inter-actions into a three-dimensional network. PMID- 22091075 TI - 2-[2-(4-Acetyl-phen-yl)hydrazinyl-idene]-1,3-diphenyl-propane-1,3-dione. AB - In the title compound, C(23)H(18)N(2)O(3), the inter-planar angle between the benzoyl units is 80.51 (6) degrees while the dihedral angles between the hydrazinyl-idene and benzoyl groups are 43.43 (6) and 54.16 (6) degrees . In the crystal, a strong resonance-assisted intra-molecular N-H?O hydrogen bond is observed. The mol-ecules form an inversion dimer via a pair of weak C-H?O hydrogen bonds and a pi-pi inter-action [centroid-centroid distance of 3.5719 (10) A]. These dimers are linked via weak C-H?O contacts, forming chains along the b axis. PMID- 22091076 TI - (5S)-3-Chloro-4-diallyl-amino-5-[(1R,2S,5R)-2-isopropyl-5-methyl-cyclo-hex yloxy]furan-2(5H)-one. AB - The title compound, C(20)H(30)ClNO(3), was obtained via a tandem asymmetric Michael addition-elimination reaction of (5S)-3,4-dichloro-5-(l-menth-yloxy) 2(5H)-furan-one and diallyl-amine in the presence of potassium fluoride. The mol ecular structure contains an approximately planar five-membered furan-one ring [maximum atomic deviation = 0.0221 (3) A] and a six-membered ring adopting a chair conformation. PMID- 22091077 TI - (E)-Methyl 2-chloro-4-dicyclo-hexyl-amino-4-oxobut-2-enoate. AB - In the title compound, C(17)H(26)ClNO(3), both cyclo-hexyl rings have chair conformations. In the crystal, mol-ecules are linked by weak inter-molecular C H?O hydrogen bonds. PMID- 22091078 TI - 5,7-Dibromo-3-trifluoro-methyl-3,4-dihydro-acridin-1(2H)-one. AB - In the title compound, C(14)H(8)Br(2)F(3)NO, the mol-ecule is disordered across an approximate non-crystallographic mirror plane, which is in the plane of the fused ring system [The tetrahedral C atom bearing the trifluormethyl substituent is disordered with site occupancy factors of 0.80 (2) and 0.20 (2)]. In the crystal, a one-dimensional stacking of mol-ecules involves inter-actions between the pyridine ring and symmetry-related Br and O atoms of adjacent mol-ecules. The stacking distance between the mean planes of adjacent mol-ecules is 3.395 (4) A. PMID- 22091079 TI - 3-Cyclo-hexyl-sulfonyl-5-iodo-2,7-dimethyl-1-benzofuran. AB - In the title compound, C(16)H(19)IO(3)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, pairs of inter-molecular I?O contacts [3.269 (2) A] link the mol-ecules into inversion dimers. These dimers are further stabilized by a slipped pi-pi inter-action between the benzene and furan rings of adjacent mol ecules [centroid-centroid distance = 3.701 (3) A, inter-planar distance = 3.372 (3) A and slippage = 1.525 (3) A]. PMID- 22091080 TI - 1,6-Bis(prop-2-yn-1-yl-oxy)naphthalene. AB - The title compound, C(16)H(12)O(2), contains two prop-2-yn-1-yl-oxy groups attached to a naphthalene ring system at the 1- and 6-positions. The crystal packing includes an inter-molecular C-H?pi inter-action between a terminal ethynyl H atom and an ethynyl group on a glide-related mol-ecule and another inter-action between an O-atom-linked methyl-ene H and an ethynyl group of a different glide-related mol-ecule. PMID- 22091081 TI - 2,2-Dimethyl-N-(2-methyl-phenyl-sulfon-yl)acetamide. AB - The asymmetric unit of the title compound, C(11)H(15)NO(3)S, contains two independent mol-ecules in which the amide bonds show a trans conformation. The C S-N-C torsion angles are -67.4 (2) and 63.8 (2) degrees in the two independent mol-ecules. In one of the mol-ecules, a methyl group is disordered over two sets of sites with a site-occupation factor of 0.661 (16) for the major occupany component. In the crystal, mol-ecules are packed into chains running along [101] through N-H?O(S) hydrogen bonds. PMID- 22091082 TI - 6-Allyl-8-meth-oxy-3-phenyl-3,4-dihydro-2H-benzo[e][1,3]oxazine. AB - In the title compound, C(18)H(19)NO(2), the allyl group is disordered over two sets of sites [occupancy ratio 0.662 (4):0.338 (4)]. The dihedral angle between the phenyl and benzene rings is 87.44 (10) degrees . The oxazinane ring adopts a sofa conformation. PMID- 22091083 TI - 2-Amino-3-carb-oxy-pyridinium nitrate. AB - In the crystal structure of the title compound, C(6)H(7)N(2)O(2) (+).NO(3) (-), the cations are linked via C-H?O hydrogen bonds, forming infinite chains running along the b axis. These chains are further linked through N-H?O, O-H?O and C-H?O hydrogen bonds to the nitrate anions, forming well-separated infinite planar layers parallel to (001). PMID- 22091084 TI - 3,3'-Dichloro-biphenyl-4,4'-diaminium sulfate. AB - In the title compound, C(12)H(12)Cl(2)N(2) (2+).SO(4) (2-), the two rings are not coplanar [dihedral angle = 48.7 (2) degrees ]. In the crystal, multiple N-H?O hydrogen-bond inter-actions are found between the ammonium and sulfate groups. PMID- 22091085 TI - (4R,11R)-9-(1-hydroxypropan-2-yl)-4,11-diphenyl-1,3,5,7,9-pentaazatri cyclo[5.3.1.0]undecane-2,6-dithione. AB - The asymmetric unit of the title compound, C(21)H(23)N(5)OS(2), contains two independent chiral mol-ecules. The two phenyl rings of one mol-ecule form a dihedral angle of 51.95 (7) degrees and the distance between their centroids is 4.345 (1) A. In the other mol-ecule, the phenyl rings form a dihedral angle of 58.79 (8) degrees with a ring centroid-centroid distance of 4.435 (2) A. An intra-molecular O-H?N hydrogen bond occurs in each independent mol-ecule. The crystal packing is stabilized by and inter-molecular N-H?O and N-H?S hydrogen bonds and C-H?S inter-actions. PMID- 22091086 TI - tert-Butyl 1-hy-droxy-piperidine-2-carboxyl-ate. AB - The title compound, C(10)H(19)NO(3), is a disubstituted piperidine bearing substituents in two equatorial positions. One of the substituents is a hy-droxy group bound to nitro-gen and the second a tert-butyl ester group bound to the carbon next to the endocyclic nitro-gen. Enanti-omers of the title compound form hydrogen-bridged dimers across a center of inversion. PMID- 22091087 TI - 1-Benzyl-3-[3-(naphthalen-2-yl-oxy)prop-yl]imidazolium hexa-fluoro-phosphate. AB - In the title salt, C(23)H(23)N(2)O(+).PF(6) (-), the PF(6) (-) anion is highly disordered (occupancy ratios of 0.35:0.35:0.3, 0.7:0.15:0.15, 0.7:0.3 and 0.35:0.35:0.15:0.15) with the four F atoms in the equatorial plane rotating about the axial F-P-F bond. The mean plane of the imidazole ring makes dihedral angles of 82.44 (17) and 14.39 (16) degrees , respectively, with the mean planes of the benzene ring and the naphthalene ring system. The crystal structure is stabilized by C-H?F hydrogen bonds. In addition, pi-pi [centroid-centroid distances = 3.7271 (19)-3.8895 (17) A] and C-H?pi inter-actions are observed. PMID- 22091088 TI - N-(2-Chloro-phen-yl)-2-({5-[4-(methyl-sulfan-yl)benz-yl]-4-phenyl-4H-1,2,4 triazol-3-yl}sulfan-yl)acetamide. AB - In the title mol-ecule, C(24)H(21)ClN(4)OS(2), the central 1,2,4-triazole ring forms dihedral angles of 89.05 (9), 86.66 (9) and 82.70 (10) degrees with the chloro-substituted benzene ring, the methyl-sulfanyl-substituted benzene ring and the phenyl ring, respectively. In the crystal, mol-ecules are linked into sheets parallel to (100) by inter-molecular N-H?N and weak C-H?O hydrogen bonds. PMID- 22091089 TI - (E)-2-(4-Chloro-benzyl-idene)indan-1-one. AB - In the title compound, C(16)H(11)ClO, the dihedral angle between the almost planar dihydro-indene ring system (r.m.s. deviation = 0.009 A) and the chloro benzene ring is 3.51 (14) degrees . In the crystal, mol-ecules are connected by C H?O and weak C-H?Cl inter-actions, forming infinite layers parallel to (101). PMID- 22091090 TI - (Z)-3alpha-(1,3-Dioxoisoindolin-2-yl)-17(20)-pregnene. AB - The title compound, C(29)H(37)NO(2), crystallized with two independent mol-ecules in an asymmetric unit in which the conformation of the cyclo-hexyl ring of the pregnene moiety bonded to the 3alpha-(1,3-dioxoisoindolin-2-yl)- ring system differs: in one mol-ecule it is in a chair conformation, while in the other it exhibits a half-chair conformation. The other six-membered rings in the pregnene moiety are in chair conformations and the five-membered rings are in envelope forms in both mol-ecules. In both mol-ecules, the 3alpha-(1,3-dioxoisoindolin-2 yl)- ring systems are individually approximately planar, with r.m.s. devtaions 0.0148 and 0.0264 A. The structure is consolidated by inter-molecular C-H?O hydrogen-bonding inter-actions involving the carbonyl O atoms and methyl, methyl ene and methyl-idyne groups, resulting in a two-dimensional structure. PMID- 22091091 TI - 1,3-Bis(pyridin-2-yl)-1H-benzimidazol-3-ium tetra-fluoridoborate. AB - The asymmetric unit of the title compound, C(17)H(13)N(4) (+).BF(4) (-), contains one half of the benzimidazolium cation and one half of the tetra-fluoridoborate anion, with crystallographic mirror planes bis-ecting the mol-ecules. One F atom of the tetra-fluoridoborate is equally disordered about a crystallographic mirror plane. In the crystal, C-H?F inter-actions link the cations and anions into layers parallel to (100). The crystal packing is further stabilized by F?pi contacts involving the tetra-fluoridoborate anions and the five-membered rings [F?centroid = 2.811 (2) A]. PMID- 22091092 TI - 2,4-Bis[(3-allyl-imidazolium-1-yl)meth-yl]mesitylene bis-(hexa fluoridophosphate). AB - In the title mol-ecular salt, C(23)H(30)N(4) (2+).2PF(6) (-), the central benzene ring of the cation makes dihedral angles of 89.80 (8) and 85.23 (7) degrees with the pendant imidazole rings. In the crystal, the cations and anions are linked by numerous C-H?F hydrogen bonds, thereby forming a three-dimensional network. PMID- 22091093 TI - 4-Methyl-1-[4-(methyl-sulfan-yl)benzyl-idene]thio-semicarbazide. AB - The title compound, C(10)H(13)N(3)S(2), is roughly planar (r.m.s. deviation = 0.086 A). In the crystal, N-H?S hydrogen bonds link the mol-ecules into (001) sheets. PMID- 22091094 TI - 4-tert-Butyl-2-(4-tert-butyl-pyridin-2-yl)pyridinium nitrate. AB - In the title compound, C(18)H(25)N(2) (+).NO(3) (-), the dihedral angle between the pyridine rings is 19.06 (10) degrees . In the crystal, the ions are linked into a three-dimensional network by N-H?O and C-H?O hydrogen-bonding inter actions. PMID- 22091095 TI - 2-(4-Chloro-phen-yl)-5-(cyclo-hex-1-en-1-yl)-3-(4-methyl-phenyl-sulfon-yl)-1 phenyl-imidazolidin-4-one. AB - In the title compound, C(28)H(27)ClN(2)O(3)S, the central imidazolidine ring adopts an envelope conformation with the C atom bearing the chloro-phenyl ring at the flap. The geometry around the S atom is distorted tetra-hedral. Three methyl ene groups of the cyclo-hexene ring are disordered over two sets of sites [site occupancies = 0.562 (10) and 0.438 (10)]. The crystal packing is stabilized by C H?pi inter-actions. PMID- 22091096 TI - 2-(4-Iodo-phen-yl)-1,2,3,4-tetra-hydro-isoquinoline-1-carbonitrile. AB - In the title compound, C(16)H(13)IN(2), the benzene ring of the tetra-hydro isoquinoline moiety makes a dihedral angle of 45.02 (9) degrees with the benzene ring of the 4-iodo-phenyl fragment. The N atom and the adjacent unsubstituted C atom of the tetra-hydro-isoquinoline unit are displaced by 0.294 (2) and 0.441 (3) A, respectively, from the plane through the remaining eight C atoms. In the crystal, pairs of adjacent mol-ecules are linked into dimers by weak inter molecular C-H?pi inter-actions. PMID- 22091097 TI - 5-Amino-1H-1,2,4-triazol-4-ium-3-carboxyl-ate hemihydrate. AB - The asymmetric unit of the title compound, C(3)H(4)N(4)O(2).0.5H(2)O, comprises two whole mol-ecules of 5-amino-1H-1,2,4-triazole-3-carb-oxy-lic acid in its zwitterionic form (proton transfer occurs from the carb-oxy-lic acid group to the N hetero-atom at position 1), plus one water mol-ecule of crystallization. The organic moieties are disposed into supra-molecular layers linked by N-H?O and N H?N hydrogen bonds parallel to the bc plane. Additional O-H?O and N-H?O hydrogen bonds involving the water mol-ecules and the organic mol-ecules lead to the formation of double-deck supra-molecular arrangements which are inter-connected along the a axis via pi-pi stacking [centroid-centroid distance = 3.507 (3) A]. PMID- 22091098 TI - 4-Phenyl-1-(prop-2-yn-1-yl)-1H-1,5-benzodiazepin-2(3H)-one. AB - 4-Phenyl-1H-1,5-benzodiazepin-2(3H)-one reacts in the pres-ence of a concentrated aqueous solution of sodium hydroxide and a quaternary ammonium salt (as catalyst) in benzene (phase transfer catalysis) with propargyl bromide, affording the title benzodiazepine derivative, C(18)H(14)N(2)O. In the mol-ecule, the mean plane of the propargyl substituent is almost perpendicular with that of the amide group [dihedral angle = 87.81 (8) degrees ]. In the crystal, the molecules are linked by C-H?O and C-H?N inter-actions. PMID- 22091099 TI - N-(3-Chloro-phen-yl)-N'-(3-methyl-phen-yl)succinamide. AB - The asymmetric unit of the title compound, C(17)H(17)ClN(2)O(2), contains one half-mol-ecule with a center of inversion at the mid-point of the central C-C bond. The amide N-H group is anti to the meta-chloro/methyl groups in the adjacent benzene rings. The dihedral angle between the benzene ring and the NH C(O)-CH(2) segment is 43.5 (1) degrees . In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into chains along the a axis. The methyl group and the Cl atom occupy the same position and were treated in a disorder model with site-occupation factors of 0.5 each. PMID- 22091100 TI - 6-Bromo-4-hydrazinyl-idene-1-methyl-3H-2lambda,1-benzothia-zine-2,2-dione. AB - In the title mol-ecule, C(9)H(10)BrN(3)O(2)S, the thia-zine ring has an envelope conformation with the S atom at the flap. The geometry around the S atom is distorted tetra-hedral. In the crystal, inversion dimers linked by pairs of N-H?N hydrogen bonds occur, generating R(2) (2)(6) ring motifs. N-H?O hydrogen bonds and C-H?O inter-actions connect the dimers, forming a three-dimentional network structure. PMID- 22091101 TI - 1-(2-Hy-droxy-eth-yl)-4-[3-(2-trifluoro-methyl-9H-thioxanthen-9-yl-idene)prop yl]piperazine-1,4-diium dichloride: the dihydro-chloride salt of flupentixol. AB - In the title compound, C(23)H(27)F(3)N(2)OS(+).2Cl(-), the piperazinediium ring adopts a chair conformation. The dihedral angle between the two outer aromatic rings of the 9H-thioxanthene unit is 40.35 (18) degrees . The F atoms in the trifluoro-methyl group are disordered over two sets of sites with occupancies of 0.803 (6) and 0.197 (6). In the crystal, mol-ecules are connected by N-H?Cl, O H?Cl C-H?O and C-H?Cl hydrogen bonds, forming chains propagating along [001]. There are also C-H?pi inter-actions present in the crystal structure. PMID- 22091102 TI - Diethyl 2,6,11-trioxo-2,3-dihydro-1H-anthra[1,2-d]imidazole-1,3-diacetate. AB - The title compound, C(23)H(20)N(2)O(7), consists of three fused six-membered rings (A, B and C) and one five-membered ring (D), linked to two ethyl acetate groups. The four fused rings are slightly folded around the O=C?C=O direction of the anthraquinone system, with a dihedral angle of 3.07 (8) degrees between the fused five- and six-membered rings (C and D) and the terminal ring (A). The planes through the atoms forming each acetate group are nearly perpendicular to the mean plane of the anthra[1,2-d]imidazole system, as indicated by the dihedral angles between them of 79.94 (9) and 85.90 (9) degrees . The crystal packing displays non-classical C-H?O hydrogen bonds. PMID- 22091103 TI - Bis(benzimidazol-1-yl)methane dihydrate. AB - The bis-(benzimidazol-1-yl)methane mol-ecule of the title compound, C(15)H(12)N(4).2H(2)O, displays a trans conformation with a twofold axis running through the methylene C atom. Two adjacent water mol-ecules are bonded to this mol-ecule through O-H?N hydrogen bonds, forming a trimer. Adjacent trimers are connected together via C-H?O inter-actions, forming a chain running along the b axis direction. Two such chains are joined together via pi-pi inter-actions [centroid-centroid distance = 3.556 (2) A], forming double chains, which are connected via the water mol-ecules through C-H?O associations, forming a sheet structure. The sheets are stacked on top of each other along the a-axis direction and connected through O-H?O and C-H?O inter-actions, forming a three-dimensional ABAB layer network structure. PMID- 22091104 TI - 3-Benzyl-5-benzyl-idene-2-sulfanylidene-1,3-thia-zolidin-4-one. AB - In the title mol-ecule, C(17)H(13)NOS(2), the essentially planar thia-zole ring (r.m.s deviation 0.005 A) forms dihedral angles of 16.85 (8) degrees and 75.02 (8) degrees with the phenyl rings. The dihedral angle between the two phenyl rings is 61.95 (9) degrees . PMID- 22091105 TI - 2-(2-Chloro-6,7-dimethyl-quinolin-3-yl)-2,3-dihydro-quinolin-4(1H)-one. AB - In the title mol-ecule, C(20)H(17)ClN(2)O, the dihedral angle between the mean plane of the quinoline ring system and the benzene ring of the dihydro quinolinone moiety is 57.84 (8) degrees . In the crystal, mol-ecules are linked into centrosymmetric dimers via pairs of inter-molecular N-H?N hydrogen bonds. These dimers are further stabilized by weak pi-pi stacking inter-actions between pyridine rings with a centroid-centroid distance of 3.9414 (12) A. PMID- 22091106 TI - (2E)-1-(5-Chloro-thio-phen-2-yl)-3-(2,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one. AB - In the title mol-ecule, C(16)H(15)ClO(4)S, the chloro-thio-phene and trimeth-oxy phenyl rings make a dihedral angle of 31.12 (5) degrees . The C=C double bond exhibits an E conformation. In the crystal, C-H?O inter-actions generate bifurcated bonds, linking the mol-ecules into chains along the b axis. PMID- 22091107 TI - 9-[(Furan-2-ylmeth-yl)amino]-5-(3,4,5-trimeth-oxy-phen-yl)-5,5a,8a,9-tetra-hydro furo[3',4':6,7]naphtho-[2,3-d][1,3]dioxol-6(8H)-one. AB - In title compound, C(27)H(27)NO(8), the dihydrofuran-2(3H)-one ring and the six membered ring fused to it both display envelope conformations. The dihedral angle between the benzene ring of the benzo[d][1,3]dioxole group and the other benzene ring is 60.59 (2) degrees . In the crystal, weak inter-molecular C-H?O hydrogen bonds link the mol-ecules into a three-dimensional network. The furan ring is disordered over two sets of sites with occupancies of 0.722 (7) and 0.278 (7). PMID- 22091108 TI - 5-(4-Chloro-benz-yl)-1H-tetra-zole. AB - In the title compound, C(8)H(7)ClN(4), the phenyl and tetra-zole rings are inclined at a dihedral angle of 67.52 (6) degrees . In the crystal, mol-ecules are linked by an N-H?N hydrogen bond into a chain structure along [010]. pi-pi inter-actions with centroid-centroid distances of 3.526 (1) A between adjacent tetra-zole rings further link the chains, forming a ribbon structure. PMID- 22091109 TI - 6-Chloro-N-methyl-N-phenyl-pyrimidine-4,5-diamine. AB - In the title compound, C(11)H(11)ClN(4), the dihedral angle between the aromatic rings is 66.47 (8) degrees . In the crystal, mol-ecules are linked by N-H?N hydrogen bonds, generating C(5) chains propagating in [010]. Slipped aromatic pi pi stacking between centrosymmetrically related pairs of pyrim-idine rings also occurs [centroid-centroid separation = 3.7634 (12)A and slippage = 1.715 A]. PMID- 22091110 TI - 2,4,5-Tris(biphenyl-2-yl)-1-bromo-benzene. AB - In the title compound, C(42)H(29)Br, the dihedral angles between the central benzene ring and the three attached benzene rings are very similar, lying in the range 52.65 (6)-57.20 (7) degrees . Of the dihedral angles between the rings of the o-biphenyl substituents, two are similar [46.34 (7) and 47.35 (7) degrees ], while the other differs significantly [64.17 (7) degrees ]. In the crystal, mol ecules are linked into centrosymmetric dimers by two weak C-H?pi inter-actions. PMID- 22091111 TI - 6-Bromo-1-methyl-4-[2-(4-methyl-benzyl-idene)hydrazinyl-idene]-3H-2lambda,1 benzothia-zine-2,2-dione. AB - In the title compound, C(17)H(16)BrN(3)O(2)S, the two fused rings are twisted by a dihedral angle of 6.61 (15) degrees . The thia-zine ring adopts a sofa conformation. The toluene ring is oriented at dihedral angles of 15.5 (2) and 20.6 (2) degrees with respect to the bromo-benzene and thia-zine rings, respectively. The benzyl-idene system is approximately planar [r.m.s. deviation = 0.0388 A]. In the cyrstal, weak inter-molecular C-H?O hydrogen bonds connects the mol-ecules into a chain along the b axis. PMID- 22091112 TI - N-(2,5-Dichloro-phen-yl)succinamic acid. AB - In the title compound, C(10)H(9)Cl(2)NO(3), the conformation of the N-H bond in the amide segment is syn with respect to the ortho-Cl atom and anti to the meta Cl atom of the benzene ring. In the crystal, inter-molecular O-H?O and N-H?O hydrogen bonds pack the mol-ecules into two types of chains along the a and b axes, respectively, leading to an overall sheet structure. The acid group in the side chain is disordered and was refined using a split model with site-occupation factors of 0.60:0.40. PMID- 22091113 TI - 1-[3-(Hy-droxy-meth-yl)phen-yl]-3-phenyl-urea. AB - In the title compound, C(14)H(14)N(2)O(2), the dihedral angle between the benzene rings is 23.6 (1) degrees . The H atoms of the urea NH groups are positioned syn to each other. In the crystal, inter-molecular N-H?O and O-H?O hydrogen bonds link the mol-ecules into a three-dimensional network. PMID- 22091114 TI - [2,7-Dimeth-oxy-8-(2-naphtho-yl)naphthalen-1-yl](naphthalen-2-yl)methanone. AB - The mol-ecule of the title compound, C(34)H(24)O(4), possesses crystallographically imposed twofold C(2) symmetry. The two 2-naphthoyl groups at the 1- and 8-positions of the central naphthalene ring are aligned almost anti parallel [5.21 (5) degrees ]. The dihedral angle between the central 2,7-dimeth oxy-naphthalene unit and the terminal naphthyl groups is 75.13 (4) degrees . In the crystal, weak C-H?O hydrogen bonds and pi-pi stacking inter-actions [centroid centroid and inter-planar distances are 3.6486 (8) and 3.3734 (5) A, respectively] are observed. PMID- 22091115 TI - 2,3-Bis(ethyl-sulfan-yl)-1,4,5,8-tetra-thia-fulvalene-6,7-dicarbonitrile. AB - In the title compound, C(12)H(10)N(2)S(6), all non-H atoms, except for those in the ethyl groups, lie in the same non-crystallographic plane, with a r.m.s. deviation of 0.0366 (5) A. In the crystal structure, mol-ecules are linked through weak C-H?N hydrogen bonds between methyl and cyano groups, forming centrosymmetric dimers. The dimers are arranged along the a axis, due to inter molecular N?S [3.337 (4) A] inter-actions. PMID- 22091116 TI - Dimethyl 3,5-diethyl-1H-pyrrole-2,4-dicarboxyl-ate. AB - The title pyrrole derivative, C(12)H(17)NO(4), consists of a pyrrole ring with two diagonally attached meth-oxy-carbonyl groups and two diagonally attached ethyl groups. The two carbonyl groups are approximately in the same plane as the pyrrole ring, making dihedral angles of 3.50 (19) and 6.70 (19) degrees . In the crystal, adjacent mol-ecules are assembled into dimers in a head-to-head mode by pairs of inter-molecular N-H?O hydrogen bonds. PMID- 22091117 TI - 3-(Diphenyl-methyl-idene)indolin-2-one. AB - The title mol-ecule, C(21)H(15)NO, has an indoline-2-one and two benzene substituent groups which are arranged in a propeller-like fashion around the central C atom. The dihedral angle between the two benzene rings is 73.32 (16) degrees and those between the benzene rings and the indoline-2-one group are 76.54 (14) and 67.69 (14) degrees . In the crystal, there is an inter-molecular N H?O hydrogen-bonding inter-action, which links the mol-ecules into chains extending along c. PMID- 22091118 TI - 2,4-Dibromo-6-[(hydroxyimino)methyl]phenol. AB - In the title compound, C(7)H(5)Br(4)NO(2), intra-molecular O-H?N hydrogen bonds are observed. In the crystal structure, inter-molecular O-H?O hydrogen bonds link the mol-ecules into dimers. PMID- 22091119 TI - N-Benzyl-4-methyl-N-(4-methyl-phen-yl)benzene-sulfonamide. AB - In the title mol-ecule, C(21)H(21)NO(2)S, the phenyl ring makes the dihedral angles of 74.13 (11) and 80.16 (11) degrees with the two benzene rings, which are inclined at an angle of 43.73 (10) degrees with respect to each other. In the crystal, mol-ecules are linked by inter-molecular C-H?O hydrogen bonds along the [010] direction. In addition, a weak C-H?pi (arene) inter-action is observed. PMID- 22091120 TI - N,N'-Bis(4-chloro-phenyl-sulfon-yl)suberamide. AB - The asymmetric unit of the title compound, C(20)H(22)Cl(2)N(2)O(6)S(2), contains one half-mol-ecule with a center of symmetry at the mid-point of the central C-C bond. The conformations of all the N-H, C=O and C-H bonds in the central amide and aliphatic segments are anti to their adjacent bonds. The mol-ecule is bent at the S atom with a C-SO(2)-NH-C(O) torsion angle of -80.6 (4) degrees . The dihedral angle between the benzene ring and the SO(2)-NH-C(O)-CH(2)-CH(2)-CH(2) segment is 79.5 (2) degrees . In the crystal, inter-molecular N-H?O(C) and N H?O(S) hydrogen bonds link the mol-ecules into chains along the b axis. PMID- 22091121 TI - 4-Chloro-N-(3,5-dimethyl-phen-yl)benzene-sulfonamide. AB - The asymmetric unit of the title compound, C(14)H(14)ClNO(2)S, contains two independent mol-ecules, which are twisted at the S atoms with C-SO(2)-NH-C torsion angles of -69.4 (7) degrees and 66.0 (8) degrees . The sulfonyl and the anilino benzene rings are tilted relative to each other by 49.0 (4) and 61.7 (3) degrees in the two mol-ecules. In the crystal, the mol-ecules are linked into chains by N-H?O hydrogen bonds. PMID- 22091122 TI - 4-Methyl-N-[(Z)-3-(4-methyl-phen-ylsulfon-yl)-1,3-thia-zolidin-2-yl-idene]benzene sulfonamide. AB - In the crystal structure of the title compound, C(17)H(18)N(2)O(4)S(3), mol ecules are connected into centrosymmetric dimers via weak inter-molecular C-H?pi inter-actions. These dimers are further connected through a series of weak C-H?O hydrogen bonds, while futher C-H?pi inter-actions involving the phenyl and thia zoline rings are also observed. The thia-zolidine ring is twisted from the benzene rings rings by dihedral angles of 79.1 (1) and 85.0 (1) degrees , while the dihedral angle between two benzene rings is 76.0 (1) degrees . PMID- 22091123 TI - 2-Chloro-methyl-1-methyl-1,3-benzimidazole. AB - The title compound, C(9)H(9)ClN(2), was prepared from the reaction of N-methyl benzene-1,2-diamine and 2-chloro-acetic acid in boiling 6 M hydro-chloric acid. The benzimidazole unit is approximately planar, the largest deviation from the mean plane being 0.008 (1) A. The Cl atom is displaced by 1.667 (2) A from this plane. The methyl group is statistically disordered with equal occupancy. PMID- 22091124 TI - Benzyl 3-[(E)-1-(pyrazin-2-yl)ethyl-idene]dithio-carbazate. AB - The title compound, C(14)H(14)N(4)S(2), was obtained from a condensation reaction of benzyl dithio-carbazate and acetyl-pyrazine. The asymmetric unit contains two independent mol-ecules, in each of which the pyrazine ring and dithio-carbazate unit are approximately co-planar, the r.m.s. deviations being 0.0304 and 0.0418 A. The mean plane is oriented with respect to the benzene ring at 49.22 (4) degrees in one mol-ecule and at 69.76 (7) degrees in the other. In the crystal, the mol-ecules are linked to each other via inter-molecular N-H?S hydrogen bonds, forming centrosymmetric supra-molecular dimers. PMID- 22091125 TI - Ethyl 2-amino-4-phenyl-4H-1-benzo-thieno[3,2-b]pyran-3-carboxyl-ate. AB - The title heterocyclic compound, C(20)H(17)NO(3)S, was synthesized by condensation of ethyl cyano-acetate with (Z)-2-benzyl-idenebenzo[b]thio-phen 3(2H)-one in the presence of a basic catalyst in ethanol. The phenyl and ester groups make dihedral angles of 77.67 (6) and 8.52 (6) degrees , respectively, with the benzothienopyran ring system [maximum r.m.s. deviation = 0.1177 (13) A]. In the crystal, centrosymmetric dimers are formed through pairs of N-H?O hydrogen bonds between the amine and ester groups. Inter-molecular C-H?N hydrogen bonds and C-H?pi inter-actions involving the thio-phene ring are also observed. PMID- 22091126 TI - Benzyl 3-[(E)-2-nitro-benzyl-idene]dithio-carbazate. AB - The title compound, C(15)H(13)N(3)O(2)S(2), was obtained from a condensation reaction of benzyl dithio-carbazate and 2-nitro-benzaldehyde. In the mol-ecule, the nearly planar dithio-carbazate fragment [r.m.s deviation = 0.0264 A] is oriented at dihedral angles of 7.25 (17) and 74.09 (9) degrees with respect to the two benzene rings. The nitro group is twisted by a dihedral angle of 22.4 (7) degrees to the attached benzene ring. The nitro-benzene ring and dithio carbazate fragment are located on the opposite sides of the C=N bond, showing an E configuration. In the crystal, mol-ecules are linked via inter-molecular N-H?S hydrogen bonds, forming centrosymmetric supra-molecular dimers. Weak C-H?pi inter action is also observed in the crystal structure. PMID- 22091127 TI - 14-Methoxy-2,16-dioxapentacyclo[7.7.5.0.0.0]henicosa-3(8),10,12,14-tetraene-7,20 dione. AB - The title compound, C(20)H(20)O(5), was synthesized from the reaction between 3 methoxysalicaldehyde and 1,3-cyclo-hexa-nedione in the presence of palladium(II) chloride. The two fused xanthene rings and one of the six-membered cyclo-hexane rings adopt envelope conformations, while the other six-membered cyclo-hexane ring is in a chair conformation. The mol-ecular packing is stabilized by weak inter-molecular C-H?O inter-actions. PMID- 22091128 TI - 4,6-Dimethyl-2-(naphthalen-1-yl)pyrimidine. AB - The asymmetric unit of the title compound, C(16)H(14)N(2), contains two independent mol-ecules in which the dihedral angles between the pyrimidine and naphthaline rings are 38.20 (5) and 39.35 (5) degrees . Inter-molecular C-H?pi contacts and pi-pi stacking inter-actions [centroid-centroid distances = 3.766 (1) and 3.792 (1) A] are present in the crystal structure. PMID- 22091129 TI - 4-{[1-(4-Bromo-phen-yl)eth-yl]amino-meth-yl}phenol. AB - The title compound, C(15)H(16)BrNO, obtained from a two-step reaction, was prepared for use in transition metal chemistry as a phenolic ligand with bulky substituents. Inter-molecular N-H?O and O-H?N hydrogen bonds are present in the crystal structure. PMID- 22091130 TI - (Acetoxy)(2-methylphenyl)methyl acetate. AB - In the title compound, C(12)H(14)O(4), the two acet-oxy groups are inclined by 57.92 (5) degrees and 62.71 (6) degrees to the benzene ring. An inter-molecular C-H?O inter-action involving the two acet-oxy groups generates a centrosymmetric dimer via an R(2) (2)(16) ring motif. PMID- 22091131 TI - (3S,12R,20S,24R)-20,24-Ep-oxy-dammarane-3,12,25-triol. AB - In the title mol-ecule, C(30)H(52)O(4), the three six-membered rings are in chair conformations, the cyclo-pentane ring is in an envelope form and the tetra-hydro furan ring has a conformation inter-mediate between half-chair and sofa. In the crystal, mol-ecules are linked by inter-molecular O-H?O hydrogen bonds into helical chains along [100]. Two intra-molecular O-H?O hydrogen bonds are also present. One C atom of the tetrahydrofuran ring and its attached H atoms are equally disordered over two sets of sites. PMID- 22091132 TI - (E)-2-[(2,4-Dihy-droxy-benzyl-idene)aza-nium-yl]-3-(1H-indol-3-yl)propano-ate monohydrate. AB - In the zwitterionic title compound, C(18)H(16)N(2)O(4).H(2)O, the dihedral angle between the planes of the benzene and indole rings is 39.20 (8) degrees . An intra-molecular N-H?O hydrogen bond generates an S(6) ring motif. In the crystal, inter-molecular hy-droxy and water O-H?O(carboxyl-ate) and N(+)-H?O(carboxyl-ate) and indole N-H?O(water) hydrogen bonds give a three-dimensional structure. PMID- 22091133 TI - 4-(4-Chloro-phen-yl)-N-[(E)-4-(dimethyl-amino)-benzyl-idene]-1,3-thia-zol-2 amine. AB - The title compound, C(18)H(16)ClN(3)S, adopts an extended mol-ecular structure. The thia-zole ring is inclined by 9.2 (1) and 15.3 (1) degrees with respect to the chloro-phenyl and 4-(dimethyl-amino)-phenyl rings, respectively, while the benzene ring planes make an angle of 19.0 (1) degrees . A weak inter-molecular C H?pi contact is observed in the crystal structure. PMID- 22091134 TI - 4-Nitro-N-phthalyl-l-tryptophan. AB - THE CRYSTAL STRUCTURE OF THE TITLE COMPOUND [SYSTEMATIC NAME: (2R)-3-(1H-indol-3 yl)-2-(4-nitro-1,3-dioxoisoindolin-2-yl)propanoic acid], C(19)H(13)N(3)O(6), an analogue of epigenetic modulator RG108, is constrained by strong hydrogen bonds between the indole N-H group and a carbonyl O atom of the phthalimide ring of a symmetry-related mol-ecule, and between the protonated O atom of the carboxyl group and a carbonyl O atom of the phthalimide ring. pi-pi stacking inter-actions with centroid-centroid distances of 3.638 (1) and 3.610 (1) A are also observed between indole and phthalimide rings. PMID- 22091135 TI - 2-Hy-droxy-N-(2-hy-droxy-eth-yl)benzamide. AB - In the title compound, C(9)H(11)NO(3), a derivative of salicyl-amide, the intra cyclic C-C-C angles span the range 117.96 (13)-121.56 (14) degrees . An intra molecular O-H?O hydro-gen bond occurs. In the crystal, inter-molecular O-H?O and N-H?O hydrogen bonds occur and C-H?O contacts connect the mol-ecules into a three dimensional network. The closest inter-centroid distance between two pi-systems is 3.8809 (10) A. PMID- 22091136 TI - (3-Amino-phen-yl)methanol. AB - In the title compound, C(7)H(9)NO, a derivative of benzyl alcohol, the endocyclic C-C-C angles are in the range 119.50 (12)-121.04 (12) degrees . In the crystal, mol-ecules are linked by N-H?O hydrogen-bond inter-actions, forming an extended two-dimensional framework parallel to ab. O-H?N inter-actions are also observed. PMID- 22091137 TI - {8-[4-(Bromo-meth-yl)benzo-yl]-2,7-dimeth-oxy-naphthalen-1-yl}[4-(bromo-meth yl)phen-yl]methanone. AB - In the title compound, C(28)H(22)Br(2)O(4), the two 4-bromo-methyl-benzoyl groups at the 1- and 8-positions of the naphthalene ring system are aligned almost anti parallel, the benzene rings forming a dihedral angle of 2.94 (16) degrees . The dihedral angles between the benzene rings and the naphthalene ring systems are 70.98 (13) and 72.89 (13) degrees . In the crystal, centrosymmetric-ally-related mol-ecules are linked into dimeric units by inter-molecular C-H?O inter-actions. PMID- 22091138 TI - [2-(4-Methylbenzoyl)phenyl](4-methylphenyl)methanone. AB - The asymmetric unit of the title compound, C(22)H(18)O(2), contains one half-mol ecule, the complete mol-ecule being generated by the operation of a crystallographic twofold rotation axis. The carbonyl group and the two C atoms attached to it forms inter-planar angles of 23.67 (7) degrees with the methyl substituted phenyl ring and 50.74 (8) degrees with the central ring. In the crystal, mol-ecules are linked into infinite chains along the b-axis direction by inter-molecular C-H?O inter-actions, generating R(2) (2)(10) graph-set motifs. PMID- 22091139 TI - Methyl 3-(1H-indol-3-yl)propano-ate. AB - The mol-ecule of the title compound, C(12)H(13)NO(2), adopts an essentially planar conformation (r.m.s. deviation = 0.057 A). In the crystal, the mol-ecules are linked by inter-molecular N-H?O hydrogen bonds, generating chains along [201]. PMID- 22091141 TI - N-(2,6-Dichloro-phen-yl)-4-methyl-benzamide. AB - In the title compound, C(14)H(11)Cl(2)NO, the two aromatic rings are nearly orthogonal to each other [dihedral angle 79.7 (1) degrees ], while the central amide core -NH-C(=O)- is nearly coplanar with the benzoyl ring [N-C-C-C torsion angles = -5.5 (3) and 1772. (2) degrees ]. In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into C(4) chains propagating in [001]. PMID- 22091140 TI - 21-Hy-droxy-pregna-1,4-diene-3,20-dione. AB - The title compound, C(21)H(28)O(3), is a fungal transformed metabolite of decoxycorticosterone acetate, consisting of four fused rings A, B, C and D. Ring A is nearly planar, with a maximum deviation of 0.010 (3) A from the least squares plane, while the trans-fused rings B and C adopt chair conformations. The five-membered ring D is in an envelope conformation. The orientation of the side chain is stabilized by an intramolecular O-H?O hydrogen bond. In the crystal, adjecent mol-ecules are linked by C-H?O hydrogen bonds into extended zigzag chains along the a axis. PMID- 22091142 TI - A triclinic polymorph of 3-nitro-anilinium chloride. AB - The asymmetric unit of the title compound, C(6)H(7)N(2)O(2) (+).Cl(-), contains two independent ion pairs. A monoclinic form of the title compound with only one ion pair in the asymmetric unit has been reported previously [Ploug-Sorensen & Andersen (1986). Acta Cryst. C42, 1813-1815]. In the crystal of the title compound, the components are linked into layers parallel to (001) by inter molecular N-H?Cl hydrogen bonds, with alternating hydro-philic and hydro-phobic regions. PMID- 22091143 TI - 2-[(4-Chloro-anilino)meth-yl]phenol. AB - In the title compound, C(13)H(12)ClNO, the dihedral angle between the two benzene ring planes is 68.71 (8) degrees . In the crystal, mol-ecules are linked by pairs of O-H?N hydrogen bonds into inversion dimers, which are further linked by intermolecular N-H?O interactions into a chain running parallel to the a axis. PMID- 22091144 TI - (E)-1-(4-Meth-oxy-phen-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one. AB - The title compound, C(19)H(20)O(5), was synthesized by reaction of 4-meth-oxy acetophenone and 3,4,5-trimeth-oxy-benzaldehyde. The aromatic rings form a dihedral angle of 36.39 (7) degrees . Two intramolecular C-H?O hydrogen bonds occur. The crystal packing features weak C-H?O inter-actions. PMID- 22091145 TI - (1R,2R,3R,4S,5S)-3-Methyl-8-oxa-bicyclo-[3.2.1]oct-6-ene-2,4-diyl diacetate. AB - The mol-ecule of the title compound, C(12)H(16)O(5), has crystallographically imposed mirror symmetry with the mirror plane passing through the endocyclic O atom and the mid-point of the double bond. In the crystal, mol-ecules are linked by C-H?O hydrogen bonds, forming chains running along the a axis. PMID- 22091146 TI - 3-Ethyl-4-methyl-1H-pyrazol-2-ium-5-olate. AB - The title compound, C(6)H(10)N(2)O, is a zwitterionic pyrazole derivative. The crystal packing is predominantly governed by a three-center iminium-amine N(+) H?O(-)?H-N inter-action, leading to an undulating sheet-like structure lying parallel to (100). PMID- 22091147 TI - 3,8-Dimethyl-acenaphthyl-ene-1,2-dione. AB - In the title compound, C(14)H(10)O(2), the acenaphthene-quinone core is essentially planar, with an r.m.s. deviation of 0.0140 A. In the crystal, mol ecules are connected by pi-pi stacking inter-actions [centroid-centroid distances = 3.766 (3), 3.839 (3) and 3.857 (3) A], forming columns parallel to the a axis. PMID- 22091148 TI - 4,4'-Dichloro-3,3',5,5'-tetra-methyl-2,2'-[(3aR,7aR/3aS,7aS)-2,3,3a,4,5,6,7,7a octa-hydro-1H-1,3-benzimidazole-1,3-di-yl)bis-(methyl-ene)]diphenol. AB - In the title compound, C(25)H(32)Cl(2)N(2)O(2), there are two intra-molecular O H? N hydrogen-bonding inter-actions between the hy-droxy groups on the aromatic rings and the two N atoms of the heterocyclic group. The cyclo-hexane ring adopts a chair conformation and the imidazolidine unit to which it is fused has a twisted envelope conformation. The asymmetric unit comprises one half-mol-ecule which is completed by a twofold rotation axis. A C-H?O inter-action is observed in the crystal structure. PMID- 22091149 TI - 1,5-Bis[1-(4-meth-oxy-phen-yl)ethyl-idene]thio-carbonohydrazide. AB - In the title mol-ecule, C(19)H(22)N(4)O(2)S, the two benzene rings form a dihedral angle of 9.16 (13) degrees . In the crystal, pairs of weak inter molecular C-H?S hydrogen bonds link the mol-ecules into centrosymmetric dimers, which are further linked through weak C-H?O inter-actions into sheets parallel to (012). PMID- 22091150 TI - 1,5-Bis(4-meth-oxy-benzyl-idene)thio-carbonohydrazide methanol monosolvate. AB - In the title compound, C(17)H(18)N(4)O(2)S.CH(3)OH, the two benzene rings in the thio-carbonohydrazide mol-ecule form a dihedral angle of 22.42 (18) degrees . Pairs of N-H?S hydrogen bonds link thio-carbonohydrazide mol-ecules into centrosymmetric dimers. Methanol solvent mol-ecules serve as donors (O-H?S and O H?N) and acceptors (N-H?O and C-H?O) of weak inter-molecular hydrogen bonds, which link further these dimers into double ribbons along the b axis. PMID- 22091151 TI - 2-[4-(4-Methylphenylsulfonyl)piperazin-1-yl]-1-(4,5,6,7-tetrahydrothieno[3,2 c]pyridin-5-yl)ethanone. AB - In the title thienopyridine derivative, C(20)H(25)N(3)O(3)S(2), the piperazine ring exhibits a chair conformation and the tetra-hydro-pyridine ring exhibits a half-chair conformation. The folded conformation of the mol-ecule is defined by the N-C-C-N torsion angle of -70.20 (2) degrees . Inter-molecular C-H?S and C H?O hydrogen bonds help to establish the packing. PMID- 22091152 TI - (E)-Ethyl 2-cyano-3-(1H-pyrrol-2-yl)acrylate. AB - All the non-H atoms of the title compound, C(10)H(10)N(2)O(2), are nearly in the same plane with a maximum deviation of 0.093 (1) A. In the crystal, adjacent mol ecules are linked by pairs of inter-molecular N-H?O hydrogen bonds, generating inversion dimers with R(2) (2)(14) ring motifs. PMID- 22091153 TI - 1,3-Dibenzyl-5-chloro-1H-benzimidazol-2(3H)-one. AB - In both independent mol-ecules of the title compound, C(21)H(17)ClN(2)O, the aromatic rings of the benzyl substituents are located on opposite sides of the benzimidazole ring systems. In one mol-ecule, the rings are aligned at 77.0 (1) and 78.1 (1) degrees with respect to the fused-ring system, whereas in the other mol-ecule the rings are aligned at 76.0 (1) and 76.9 (1) degrees . There is an inter-molecular Cl?O contact of 3.086 (1) A. PMID- 22091154 TI - 1,3-Bis[3-(1,3-dioxoisoindolin-2-yl)prop-yl]-1H-anthra[1,2-d]imidazole-2,6,11(3H) trione. AB - The title compound, C(37)H(26)N(4)O(7), is a 1H-anthra[2,1-d]imidazole-2,6,11(3H) trione derivative having isoindolindionylpropyl substitutents attached to the imidazole N atoms. The anthraquinone fragment is buckled, the dihedral angle between the two benzene rings being 1.6 (1) degrees . The two isoindoline rings of the substituents of the imidazole ring are positioned on opposite sides of the five-membered ring; these are nearly mutually perpendicular [dihedral angle between isoindoline rings = 88.3 (1) degrees ]. PMID- 22091155 TI - 1,3-Bis(naphthalen-2-ylmeth-yl)-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione. AB - The title compound, C(37)H(24)N(2)O(3), is a 1H-anthra[2,1-d]imidazole-2,6,11(3H) trione derivative having naphthyl-methyl substitutents attached to the imidazole N atoms. The anthraquinone part of the mol-ecule is somewhat folded along the the line connecting the carbonyl bonds. The dihedral angle between the two benzene rings is 7.8 (1) degrees . The two naphthyl systems of the substituents of the imidazole ring are positioned on the same side of the five-membered ring; these are approximately coplanar, the dihedral angle between the napthyl systems being 4.3 (2) degrees . PMID- 22091156 TI - (E)-N'-[4-(Dimethyl-amino)-benzyl-idene]-4-methyl-benzohydrazide methanol monosolvate. AB - In the title compound, C(17)H(19)N(3)O.CH(3)OH, the hydrazone mol-ecule exists in a trans geometry with respect to the methyl-idene unit and the dihedral angle between the two substituted benzene rings is 42.6 (2) degrees . In the crystal, the components are linked through N-H?O and O-H?O hydrogen bonds, forming [100] chains of alternating hydrazone and methanol mol-ecules. PMID- 22091157 TI - N-[Amino-(azido)-meth-ylidene]-4-methyl-benzene-sulfonamide. AB - In the title mol-ecule, C(8)H(10)N(5)O(2)S, the amino-(azido)-methyl and p toluene-sulfonyl moieties are inclined almost at right angles with respect to each other, making a dihedral angle of 83.49 (6) degrees . An intra-molecular N H?O hydrogen bond gives rise to the formation of six-membered ring with graph-set motif S(6). In the crystal, inter-molecular N-H?O hydrogen bonding is responsible for the formation of dimers about inversion centers, which are linked through another N-H?O inter-action along the b axis. PMID- 22091158 TI - 5-Chloro-6-hy-droxy-7,8-dimethyl-chroman-2-one. AB - In the title mol-ecule, C(11)H(11)ClO(3), the fused pyran ring adopts a half chair conformation. In the crystal, inter-molecular O-H?O hydrogen bonds link mol ecules into chains along [100]. These chains are inter-connected by weak inter molecular C-H?O contacts which generate R(2) (2)(8) ring motifs, forming sheets parallel to (001). Tetra-gonal symmetry generates an equivalent motif along b. Furthermore, the sheets are linked along the c axis by offset pi-pi stacking inter-actions involving the benzene rings of adjacent mol-ecules [with centroid centroid distances of 3.839 (2) A], together with an additional weak C-H?O hydrogen bond, resulting in an overall three-dimensional network. PMID- 22091159 TI - N-tert-Butyl-2-methyl-propanamide. AB - The title compound, C(8)H(17)NO, crystallizes with two independent mol-ecules in the asymmetric unit. In the crystal, inter-molecular N-H?O hydrogen bonding is observed between neighboring mol-ecules, forming continuous mol-ecular chains along the c-axis direction. PMID- 22091160 TI - 2,2'-(Propane-1,3-di-yl)bis-(2H-indazole). AB - The title mol-ecule, C(17)H(16)N(4), is a bis-indazole crystallized in the rare 2H-tautomeric form. Indazole heterocycles are connected by a propane C(3) chain, and the mol-ecule is placed on a general position, in contrast to the analogous compound with a central C(2) ethane bridge, which was previously found to be placed on an inversion center in the same space group. In the title mol-ecule, indazole rings make a dihedral angle of 60.11 (7) degrees , and the bridging alkyl chain displays a trans conformation, resulting in a W-shaped mol-ecule. In the crystal, mol-ecules inter-act weakly through pi-pi contacts between inversion related pyrazole rings, with a centroid-centroid separation of 3.746 (2) A. PMID- 22091161 TI - (Z)-Ethyl 2-cyano-2-{2-[5,6-dimethyl-4-(thio-phen-2-yl)-1H-pyrazolo-[3,4 b]pyridin-3-yl]hydrazinylidene}acetate. AB - In the title compound, C(17)H(16)N(6)O(2)S, an intra-molecular N-H?O inter-action generates an S(6) ring. The pyridine ring makes a dihedral angle of 71.38 (11) degrees with the thio-phene ring. In the crystal, mol-ecules are linked by a pair of N-H?N hydrogen bonds, forming an inversion dimer. The dimers are stacked in columns along the b axis through weak inter-molecular C-H?N hydrogen bonds. PMID- 22091162 TI - (E)-2-[4-(Trifluoro-meth-oxy)benzyl-idene]indan-1-one. AB - In the title compound, C(17)H(11)F(3)O(2), the dihydro-indene ring is approximately planar with a maximum deviation of 0.024 (2) A and makes a dihedral angle of 3.17 (8) A with the adjacent benzene ring. In the crystal, mol-ecules are inter-connected by C-H?O inter-actions, forming an infinite chain along the c axis. PMID- 22091163 TI - (1,2-Dicarba-closo-dodeca-boran-yl)trimethyl-methanaminium iodide. AB - The title compound, [1-(CH(3))(3)NCH(2)-1,2-C(2)B(10)H(11)](+).I(-) or C(6)H(22)B(10)N(+).I(-), was obtained by the reaction of (1,2-dicarba-closo dodeca-boran-yl)dimethyl-methanamine with methyl iodide. The asymmetric unit contains two iodide anions and two (o-carboran-yl)tetra-methyl-ammonium cations. The bond lengths and angles in the carborane cage are within normal ranges, but the N-C(methyl-ene)-C(cage) angle is very large [120.2 (2) degrees ] because of repulsion between the carborane and tetra-methyl-ammonium units. In the crystal, ions are linked through C-H?I hydrogen bonds. PMID- 22091164 TI - N-(2,4,6-Trichloro-phen-yl)maleamic acid. AB - In the crystal structure of the title compound, C(10)H(6)Cl(3)NO(3), the conformation of the amide bond is trans. The C=O and O-H bonds of the acid group are in the relatively rare anti position to each other. This is a consequence of the intra-molecular O-H?O hydrogen bond donated to the amide carbonyl group stabilizing the mol-ecular structure. In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into zigzag chains along the c axis. PMID- 22091165 TI - 3-[(1-Isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)amino]-benzoic acid. AB - In the title compound, C(21)H(20)N(4)O(2), the statistically planar 1H-limidazole ring [maximum deviation = 0.003 (1) A] makes dihedral angles of 1.33 (9) and 8.23 (7) degrees , respectively, with the essentially planar fused pyridine ring [maximum devation = 0.018 (1) A] and the pendant benzene ring, which is attached to the pyridine ring by an -NH- group. An intra-molecular C-H?N inter-action, which generates an S(6) ring, helps to estalish the mol-ecular conformation. In the crystal, the mol-ecules are linked by N-H?O, C-H?O and O-H-N hydrogen bonds, which generate bifurcated R(1) (2)(6) and R(2) (2)(9) ring motifs, resulting in supra-molecular [001] chains. The crystal structure also features weak pi-pi stacking [centroid-centroid distance = 3.5943 (9) A] and C-H?pi inter-actions. PMID- 22091166 TI - (E)-2-[4-(Dimethyl-amino)-styr-yl]-1-methyl-pyridinium triiodide. AB - The asymmetric unit of the title compound, C(16)H(19)N(2) (+).I(3) (-), contains a (E)-2-[4-(dimethyl-amino)-styr-yl)-1-methyl-pyrid-in-ium cation and half each of two triiodide anions. The complete triiodide anions are each generated by inversion symmetry. The planar cation has all of its eighteen non-H atoms situated on a mirror plane. In the crystal, the cations are stacked along the b axis by pi-pi inter-actions with a centroid-centroid distance of 3.5757 (13) A. The triiodide anions are located between the cations. The crystal structure is further consolidated by short C?C [3.322 (9)-3.3952 (19) A] contacts. PMID- 22091167 TI - (R)-Methyl {[(2-carb-oxy-bicyclo-[2.2.2]octan-1-yl)-ammonio]-methyl}-phos-phon ate dichloro-methane 0.25-solvate. AB - The carb-oxy-lic acid mol-ecule of the title compound, C(11)H(20)NO(5)P.0.25CH(2)Cl(2), exists as a zwitterion with the H atom of the phospho-nate group being transferred to the imine N atom. In the asymmetric unit, there are two crystallographically independent acid mol-ecules adopting the same absolute configuration and differing slightly in their geometrical parameters. In each mol-ecule, the imino and carboxyl groups are connected via an intra molecular N-H?O hydrogen bond. Inter-molecular O-H?O and N-H?O hydrogen bonds induce the formation of layers parallel to the ab plane. The dichloro-methane solvent mol-ecule, with a site occupancy of 0.5, is located between the layers. PMID- 22091168 TI - Pyridine-2,3-diamine. AB - The mol-ecule of the title pyridine derivative, C(5)H(7)N(3), shows approximately non-crystallographic C(s) symmetry. Intra-cyclic angles cover the range 117.50 (14)-123.03 (15) degrees . In the crystal, N-H?N hydrogen bonds connect mol ecules into a three-dimensional network. The closest inter-centroid distance between two pi-systems occurs with the c-axis repeat at 3.9064 (12) A. PMID- 22091169 TI - Benzyl N-(1-{N'-[(E)-2,3-dihy-droxy-benzyl-idene]hydrazinecarbon-yl}-2-hy-droxy eth-yl)carbamate dihydrate. AB - The organic mol-ecule in the title dihydrate, C(18)H(19)N(3)O(6).2H(2)O, adopts a twisted U-shape with the major twists evident about the chiral C atom [the C-N-C C torsion angle is -88.2 (4) degrees ] and about the oxygen-benzyl bond [C-O-C-C = 74.2 (4) degrees ]. The conformation about the imine bond [1.290 (4) A] is E and an intra-molecular O-H?N hydrogen bond helps to establish the near coplanarity of the hy-droxy-benzene and hydrazine groups. The crystal packing features O-H?O and N-H?O hydrogen bonds, leading to two-dimensional supra molecular arrays in the ab plane with weak C-H?pi connections between the arrays. PMID- 22091170 TI - (2Z)-3-(4-Chloro-anilino)-1-(5-hy-droxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)but-2 en-1-one. AB - With the exception of the terminal benzene rings, the atoms in the title compound, C(20)H(18)ClN(3)O(2), are approximately coplanar (r.m.s. deviation = 0.0495 A). The benzene/chloro-benzene rings form dihedral angles of 3.02 (4) and 41.59 (5) degrees , respectively, with this plane. The hy-droxy, amino and carbonyl groups all lie to the same side of the mol-ecule, enabling the formation of intra-molecular O-H?O and N-H?O hydrogen bonds that close S(6) rings. The configuration about the 2-butene bond is Z. Supra-molecular chains mediated by C H?Cl inter-actions and aligned along the c axis are found in the crystal packing. These assemble into layers that are connected by weak pi-pi inter-actions between centrosymmetrically related chloro-benzene rings [3.8156 (9) A]. PMID- 22091171 TI - Resorcinol-triethyl-enediamine (1/1). AB - The title co-crystal, C(6)H(12)N(2).C(6)H(6)O(2), is composed of neutral resorcinol and triethyl-enediamine mol-ecules in which the resorcinol mol-ecules came from the in situ deca-rboxylation of 2,4-dihy-droxy-benzoic acid. In the crystal, the components are connected by O-H?N hydrogen bonds, forming a chain in the b-axis direction. PMID- 22091172 TI - 4,4,5,5-Tetra-methyl-1,3,2lambda-dioxa-phospho-lan-2-one. AB - The five-membered ring in the title compound, C(6)H(13)O(3)P, exists in an envelope conformation with one of the ring C atoms at the flap position. The coordination geometry around the P atom is a distorted tetra-hedron. The crystal structure is stabilized by several weak C-H?O and P-H?O hydrogen bonds, forming a three-dimensional network. PMID- 22091173 TI - N-(4-Chloro-phen-yl)-2,4-dimethyl-benzene-sulfonamide. AB - Mol-ecules of the title compound, C(14)H(14)ClNO(2)S, are bent at the S atom with a C-SO(2)-NH-C torsion angle of 57.7 (2) degrees . The benzene rings are rotated relative to each other by 68.1 (1) degrees . In the crystal, N-H?O(S) hydrogen bonds pack the mol-ecules into infinite chains parallel to the b axis. PMID- 22091174 TI - N,N'-Bis(4-methyl-phenyl-sulfon-yl)-suberamide. AB - In the crystal structure of the title compound, C(22)H(28)N(2)O(6)S(2), the asymmetric unit contains one half mol-ecule with a center of symmetry at the mid point of the central C-C bond. The conformations of all the N-H, C= O and C-H bonds in the central amide and aliphatic segments are anti to their adjacent bonds. The mol-ecule is bent at the S atom with an C-SO(2)-NH-C(O) torsion angle of -76.4 (3) degrees . The dihedral angle between the benzene ring and the SO(2) NH-C(O) segment in the two halves of the mol-ecule is 67.2 (1) degrees . In the crystal, N-H?O(C) inter-molecular hydrogen bonds link the mol-ecules into chains along the b axis. PMID- 22091175 TI - 2-[(1,3-Benzodioxol-5-yl-methyl-idene)amino]-4,5,6,7-tetra-hydro-1-benzothio phene-3-carbonitrile. AB - The title compound, C(17)H(14)N(2)O(2)S, crystallizes with two roughly planar mol ecules in the asymmetric unit, in which the dihedral angles between the 1,3 benzodioxole-5-carbaldehyde moiety and the heterocyclic five-membered ring are 3.76 (5) and 5.33 (12) degrees . In each mol-ecule, a short C-H?S contact generates an S(5) ring. In the crystal, pairs of mol-ecules are linked by a weak C-H?N inter-action, forming dimers. PMID- 22091176 TI - 4-[(Anthracen-9-yl-methyl-idene)amino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H) one. AB - In the title compound, C(26)H(21)N(3)O, the phenyl ring of the 4-amino-anti pyrine group and the heterocyclic five-membered ring along with its substituents, except for the N-bound methyl group (r.m.s. deviation = 0.0027 A), form a dihedral angle of 54.20 (5) degrees . Two S(6) ring motifs are formed due to intra-molecular C-H?N and C-H?O hydrogen bonds. In the crystal, mol-ecules are linked into supra-molecular chains along the a-axis direction via C-H?O contacts. PMID- 22091177 TI - 2-Hy-droxy-N-(4-meth-oxy-benz-yl)-4-nitro-anilinium chloride. AB - The crystal structure of the title compound, C(14)H(15)N(2)O(4) (+).Cl(-), can be described as being composed of layers containing both cations and anions that are staggered along [010]. Two types of the hydrogen bonds are observed, viz. cation anion and cation-cation. The chloride anions are acceptors of the strong hydrogen bonds donated by the secondary amine and the hy-droxy groups. The packing is also stabilized by weak C-H?O inter-molecular hydrogen bonds. An intra-molecular N-H?O inter-action also occurs. PMID- 22091178 TI - 3-Amino-N'-(2-oxoindolin-3-yl-idene)benzohydrazide. AB - The title compound, C(15)H(12)N(4)O(2), contains two substituted benzohydrazide and indole rings linked via a C=N double bond. The dihedral angle between the benzene ring and the indole ring system is 11.38 (10) degrees . The mol-ecular structure is stabilized by an intra-molecular N-H?O hydrogen bond, forming a six membered ring. The crystal structure is consolidated by inter-molecular N-H?O and C-H?O inter-actions, which result in sheets. PMID- 22091179 TI - p-Tolyl bis-(cyclo-hexyl-amido)-phosphinate. AB - The P atom in the title mol-ecule, C(19)H(31)N(2)O(2)P, is in a distorted tetra hedral configuration with the bond angles in the range 101.48 (10)-118.58 (9) degrees . The N-H units have a syn orientation with respect to one another. In the crystal, mol-ecules are connected via two different inter-molecular N-H?O(P) hydrogen bonds into chains along the a axis in which the O atom of the P=O group acts as a double acceptor. PMID- 22091180 TI - 2,5-Bis[2-(4-methyl-phen-yl)ethyn-yl]benzyl methacrylate. AB - In the title bis-tolane derivative, C(29)H(24)O(2), the central benzene ring forms dihedral angles of 29.12 (9) and 26.46 (9) degrees with the other two benzene rings. The dihedral angle between two terminal benzene rings is 55.58 (8) degrees . PMID- 22091181 TI - Diisopropyl-ammonium methane-sulfonate. AB - The title molecular salt, C(6)H(16)N(+).CH(3)SO(3) (-), has been determined at 150 K. Two diisopropyl-ammonium cations (dipH) and two anions form N-H?O hydrogen bonded cyclic dimers lying around centers of symmetry. Only two of the three O atoms of the methane-sulfonate anion are involved in hydrogen bonding, resulting in slightly longer S-O bond lengths. The title structure represents an example of a sulfonate anion that is part of a hydrogen-bonding R(4) (4)(12) graph-set motif, which is well known for related dipH acetates. Additionally, the Raman and the IR spectroscopic data for the title compound are presented. PMID- 22091182 TI - N-Acryloyl glycinamide. AB - The mol-ecule of the title compound [systematic name: N-(carbamoylmeth-yl)prop-2 enamide], C(5)H(8)N(2)O(2), which can be radically polymerized to polymers with thermoresponsive behavior in aqueous solution, consists of linked essentially planar acryl-amide and amide segments [maximum deviations = 0.054 (1) and 0.009 (1) A] with an angle of 81.36 (7) degrees between their mean planes. In the crystal, N-H?O hydrogen bonding leads to an infinite two-dimensional network along (100). PMID- 22091183 TI - Tetra-methyl-ammonium borohydride from powder data. AB - In the crystal structure of the title compound, C(4)H(12)N(+).BH(4) (-), the tetra-methyl-ammonium cations are situated on special positions with site symmetry [Formula: see text]m2. The borohydride anions are situated on special positions with 4mm site symmetry and show rotational disorder around the fourfold axis. PMID- 22091184 TI - 1-[(Z)-2-Phenyl-hydrazin-1-yl-idene]-1-(piperidin-1-yl)propan-2-one. AB - A Z configuration about the imine bond [1.3025 (18) A] in the title compound, C(14)H(19)N(3)O, allows for the formation of an intra-moleclar N-H?N hydrogen bond between the hydrazone H and piperidine N atoms; the carbonyl group is disposed to lie over the piperidine residue, which is in a chair form. A twist between the terminal benzene ring and the hydrazine residue is seen [N-N-C-C torsion angle = 163.81 (12) degrees ]. Helical supra-molecular chains along the c axis mediated by N-H?O hydrogen bonds are the most prominent feature of the crystal packing. The chains are connected into layers lying in the ac plane by weak C-H?pi contacts involving two methyl-ene H atoms and an adjacent benzene ring. PMID- 22091185 TI - 2,13-Dibenzyl-5,16-diethyl-2,6,13,17-tetra-aza-tricyclo-[16.4.0.0]docosan-2-ium nitrate. AB - One of the tertiary amine atoms has been protonated in the title salt, C(36)H(57)N(4) (+).NO(3) (-). The four N atoms of the macrocycle are almost coplanar (r.m.s. deviation = 0.0053 A), a result correlated with the formation of intra-molecular N-H?N and N-H?(N,N) hydrogen bonds. With respect to this plane, the benzyl groups lie to either side; a similar arrangement pertains for the cyclo-hexyl rings (each with a chair conformation). Helical supra-molecular chains are evident in the crystal, whereby alternating cations and anions are linked by C-H?O inter-actions. The chains are consolidated into supra-molecular arrays in the ab plane via C-H?pi contacts involving both benzene rings. PMID- 22091186 TI - N,N'-Bis[(E)-2,4,6-trimethyl-benzyl-idene]ethane-1,2-diamine. AB - The title compound, C(22)H(28)N(2), which is a double imine derived from ethane 1,2-diamine and mesityl aldehyde, has crystallographic inversion symmetry, with both C=N bonds E configured. The dihedral angle between the mesityl ring system and the imide functional group is 23.89 (17) degrees . PMID- 22091187 TI - 2-[(4-Formyl-phen-yl)(hy-droxy)meth-yl]acrylonitrile. AB - In the title compound, C(11)H(9)NO(2), the mean planes formed by the phenyl and acryl group are almost orthogonal to each other, with a dihedral angle of 88.61 (7) degrees . The carbonitrile side chain is almost linear, the C-C-N angle being 179.54 (16) degrees . In the crystal, mol-ecules are linked by inter-molecular O H?O inter-actions into infinite chains running parallel to the b axis. PMID- 22091188 TI - (2-Benzoyl-phen-yl)(3,4-dimethyl-phen-yl)methanone. AB - In the title compound, C(22)H(18)O(2), the central benzene ring forms dihedral angles of 76.0 (1) and 73.1 (1) degrees with the phenyl ring and dimethyl substituted benzene ring, respectively. The carbonyl-group O atoms deviate significantly from the phenyl ring and the dimethyl-substituted benzene ring [ 0.582 (12) and 0.546 (12) A, respectively]. The crystal packing is stabilized by C-H?pi inter-actions. PMID- 22091189 TI - N-(3-Chloro-phen-yl)-2,4-dimethyl-benzene-sulfonamide. AB - In the mol-ecule of the title compound, C(14)H(14)ClNO(2)S, the N-H bond is in a syn position with respect to the meta-Cl atom in the aniline ring. The mol-ecule is twisted about the N-S bond with a C-SO(2)-NH-C torsion angle of 44.55 (17) degrees . The two aromatic rings are inclined relative to each other by 66.2 (1) degrees . In the crystal, N-H?O hydrogen bonds link the mol-ecules into infinite chains parallel to the b axis. PMID- 22091190 TI - N,N'-Bis(4-chloro-phenyl-sulfon-yl)-adipamide. AB - In the title compound, C(18)H(18)Cl(2)N(2)O(6)S(2), the asymmetric unit contains half a mol-ecule with a center of symmetry at the mid-point of the central C-C bond. The dihedral angle between the benzene ring and the SO(2)-NH-C(O) segment in the two halves of the mol-ecule is 83.5 (2) degrees . In the crystal, N-H?O(S) inter-molecular hydrogen bonds link the mol-ecules into infinite chains running along the c axis. The O atom involved in the hydrogen bond has a longer S-O bond than the other O atom bonded to S [1.403 (4) versus 1.361 (4) A]. PMID- 22091191 TI - (2-Hy-droxy-4-meth-oxy-phen-yl)(2-hy-droxy-phen-yl)methanone. AB - The title compound, C(14)H(12)O(4), is an asymmetric substitution product of benzophenone. Both hy-droxy groups are orientated towards the O atom of the keto group. Intra-molecular as well as inter-molecular O-H?O hydrogen bonds can be observed in the crystal structure, with the latter connecting the mol-ecules into chains along the crystallographic b axis. C-H?O contacts [C?O = 3.3297 (18) A] are also apparent. The closest centroid-centroid distance between two aromatic systems is 4.9186 (9) A. PMID- 22091192 TI - Heptane-1,7-diaminium sulfate mono-hydrate. AB - The crystal structure of the title compound, C(7)H(20)N(2) (2+).SO(4) (2-).H(2)O, is presented, with particular focus on the packing arrangement in the crystal structure and selected hydrogen-bonding inter-actions that the compound forms. The crystal structure exhibits parallel stacking of the diammonium dication in its packing arrangement, together with inorganic-organic layering that is typical of these n-alkyl-diammonium salts. An intricate three-dimensional hydrogen bonding network exists in the crystal structure where the hydrogen bonds link the cation and anion layers together through the sulfate anions and the water mol ecules. PMID- 22091193 TI - 5,5'-(Disulfanedi-yl)bis-(1-methyl-1H-tetra-zole). AB - In the title mol-ecule, C(4)H(6)N(8)S(2), two tetra-zole rings linked by a disulfide bridge form a dihedral angle of 71.32 (7) degrees [C-S-S-C torsion angle = -80.51 (10) degrees ]. In the crystal, strong inter-molecular pi-pi inter actions between the tetra-zole rings [centroid-centroid distance = 3.285 (3) A] link pairs of mol-ecules into centrosymmetric dimers. Weak inter-molecular C-H?N hydrogen bonds further link these dimers, related by translation in the [100] direction, into columns. PMID- 22091194 TI - Cyclo-hexyl-ammonium 4-meth-oxy-benzoate. AB - In the crystal of the title molecular salt, C(6)H(14)N(+).C(8)H(7)O(3) (-), strong N-H?O hydrogen bonds are formed between the ammonium H atoms and the carboxyl-ate O atoms. The resulting supra-molecular structure is based on chains running in the [010] direction. The dihedral angle between the -CO(2) group and the benzene ring is 8.94 (17) degrees and the methoxy C atom deviates by 1.374 A from the ring. PMID- 22091195 TI - N-[2-(3,4-Dimeth-oxy-phen-yl)eth-yl]-N,4-dimethyl-benzene-sulfonamide. AB - In the title compound, C(18)H(23)NO(4)S, the dihedral angle between the two aromatic rings is 29.14 (7) degrees . The S atom has a distorted tetra-hedral geometry [106.15 (9)-119.54 (10) degrees ]. The crystal structure exhibits weak C H?O and pi-pi inter-actions. PMID- 22091196 TI - Methyl 2-(3a,8a-dimethyl-4-oxodeca-hydro-azulen-6-yl)acrylate. AB - The title compound, C(16)H(24)O(3), was synthesized from ilicic acid, which was isolated from the aerial part of Inula viscosa- (L) Aiton [or Dittrichia viscosa- (L) Greuter]. The asymmetric unit contains two independent mol-ecules, in each of which the seven-membered ring shows a chair conformation, whereas the five membered ring presents disorder. In the two molecules, three C atoms in the five membered ring are disordered over two positions with site-occupancy factors of 0.53/0.47 and 0.83/0.17. The dihedral angle between the two rings is different in the two mol-ecules [31.7 (3) and 47.7 (7) degrees ]. The crystal structure is stabilized by weak inter-molecular C-H?O hydrogen-bond inter-actions. PMID- 22091197 TI - N'-(3,4-Dimeth-oxy-benzyl-idene)-3,5-dihy-droxy-benzohydrazide methanol monosolvate. AB - In the title compound, C(16)H(16)N(2)O(5).CH(4)O, the two benzene rings in the Schiff base mol-ecule form a dihedral angle of 17.1 (1) degrees . In the crystal, inter-molecular O-H?O hydrogen bonds link the components into corrugated sheets parallel to the (101) plane. PMID- 22091198 TI - (R)-(+)-2-{[(3-Methyl-4-nitro-pyridin-2-yl)meth-yl]sulfin-yl}-1H-benzimidazole. AB - The title compound, C(14)H(12)N(4)O(3)S, is an inter-mediate of Dexlansoprazole, a proton pump inhibitor (PPI) mainly developed for anti-ulcer activity. The absolute configuration of the title compound was determined as R. The crystal structure reveals that the mol-ecules form chains along the b axis through N-H?N and C-H?O hydrogen-bonded dimers. These chains are connected via weak C-H?O hydrogen bonds. PMID- 22091199 TI - 7-Benzyl-2-[(cyclo-propyl-meth-yl)amino]-3-phenyl-5,6,7,8-tetra-hydro pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one. AB - There are two independent mol-ecules in the asymmetric unit of the title compound, C(26)H(26)N(4)OS. In each mol-ecule, the thienopyrimidine fused-ring system is essentially planar with a maximum deviation of 0.0409 (18) for the N atom. In one mol-ecule, this ring system forms diherdral angles of 84.8 (1) and 67.6 (1) degrees with the adjacent phenyl and benzyl rings, respectively, while the corresponding angles in the other mol-ecule are 77.9 (1) and 66.5 (1) degrees . PMID- 22091200 TI - Eucomic acid methanol monosolvate. AB - IN THE CRYSTAL STRUCTURE OF THE TITLE COMPOUND [SYSTEMATIC NAME: 2-hy-droxy-2-(4 hy-droxy-benz-yl)butane-dioic acid methanol monosolvate], C(11)H(12)O(6).CH(3)OH, the dihedral angles between the planes of the carboxyl groups and the benzene ring are 51.23 (9) and 87.97 (9) degrees . Inter-molecular O-H?O hydrogen-bonding inter-actions involving the hy-droxy and carb-oxy-lic acid groups and the methanol solvent mol-ecule give a three-dimensional structure. PMID- 22091201 TI - 1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-aminium chloride-thio-urea (1/1). AB - In the title compound, C(11)H(14)N(3)O(+).Cl(-).CH(4)N(2)S, the components are connected into a two-dimensional polymeric structure parallel to (001) via N H?Cl, N-H?O, N-H?S and C-H?S hydrogen bonds. The dihedral angle between the phenyl and 2,3-dihydro-1H-pyrazole rings is 44.96 (7) degrees . PMID- 22091202 TI - 1,2-Bis[5-(9-ethyl-9H-carbazol-3-yl)-2-methyl-thio-phen-3-yl]-3,3,4,4,5,5-hexa fluoro-cyclo-pentene. AB - The title compound, C(43)H(32)F(6)N(2)S(2), is a new symmetrical photochromic diaryl-ethene derivative with 9-ethyl-carbazol-3-yl substituents. The mol-ecule adopts a photoactive anti-parallel conformation [Irie (2000). Chem. Rev.100, 1685 1716; Kobatake et al. (2002). Chem. Commun. pp. 2804-2805], with a dihedral angle between the mean planes of the two thio-phene rings of 56.23 (6) degrees . The distance between the two reactive C atoms is 3.497 (3) A. In the crystal, two mol ecules are associated through a pair of C-H?F inter-molecular hydrogen bonds, forming a centrosymmetric dimer. Dimers are linked by weak pi-pi inter-actions [centroid-centroid distance = 3.8872 (13) A], forming chains along the c axis. PMID- 22091203 TI - 3-Hy-droxy-4-(3-hy-droxy-phen-yl)-2-quinolone monohydrate. AB - In the title compound, also known as viridicatol monohydrate, C(15)H(11)NO(3).H(2)O, the dihedral angle between the benzene ring and quinoline ring system is 64.76 (5) degrees . An intra-molecular O-H?O hydrogen bond occurs. The crystal structure is stabilized by classical inter-molecular N-H?O and O-H?O hydrogen bonds and weak pi-pi inter-actions with a centroid-centroid distance of 3.8158 (10) A. PMID- 22091204 TI - (E)-Methyl 3-(1H-indol-2-yl)acrylate. AB - The title compound, C(12)H(11)NO(2), is close to being planar (r.m.s. deviation for the non-H atoms = 0.033 A). In the crystal, mol-ecules are linked by N-H?O hydrogen bonds, generating C(7) chains running along the b axis. A weak C-H?O interaction helps to establish the packing. PMID- 22091205 TI - N'-(5-Bromo-2-hy-droxy-benzyl-idene)-4-nitro-benzohydrazide methanol monosolvate. AB - In the title compound, C(14)H(10)BrN(3)O(4).CH(4)O, the benzohydrazide mol-ecule is nearly planar [maximum deviation = 0.110 (2) A]. The mean planes of the two benzene rings make a dihedral angle of 8.4 (3) degrees . In the benzohydrazide mol-ecule, there is an intra-molecular O-H?N hydrogen bond and the NH group is hydrogen bonded to the methanol solvent mol-ecule. In the crystal, inter molecular O-H?O hydrogen bonds involving the methanol solvent mol-ecule link the benzohydrazide mol-ecules to form chains which propagate along the a axis. PMID- 22091206 TI - 2,4-Dibromo-naphthalen-1-ol. AB - In the essentially planar (r.m.s. deviation = 0.023 A) title compound, C(10)H(6)Br(2)O, an intra-molecular O-H?Br hydrogen bond generates an S(5) ring. In the crystal, mol-ecules are linked by an ?O-H?O-H?O- C(2) chain extending along [100], which involves the same H atom that participates in the intra molecular hydrogen bond. Aromatic pi-pi inter-actions [centroid-centroid separation = 3.737 (4) A] help to consolidate the packing. PMID- 22091207 TI - Methyl 2-{[(3-methyl-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl-idene)(thio-phen 2-yl)meth-yl]amino}-3-phenyl-propionate. AB - In the title compound, C(25)H(23)N(3)O(3)S, an intra-molecular N-H?O inter-action generates an S(6) ring, which stabilizes the enamine-keto form of the compound. This S(6) ring and the pyrazole ring are essentially coplanar, making a dihedral angle of 1.49 (6) degrees . The bond lengths within the S(6) ring of the mol ecule lie between classical single- and double-bond lengths, indicating extensive conjugation. The structure exhibits a thienyl-ring flip disorder, with occupancy factors in the ratio 64.7 (3):35.3 (3). PMID- 22091208 TI - N-[Bis(morpholin-4-yl)phosphino-yl]-2-chloro-2,2-difluoro-acetamide. AB - The asymmetric unit of the title compound, C(10)H(17)ClF(2)N(3)O(4)P, consists of two independent mol-ecules in each of which the P atom adopts a distorted tetra hedral environment with the P=O and N-H units in a syn orientation with respect to one another. Both morpholine rings in one of the phospho-ramide mol-ecules are disordered over two sets of sites, with site occupancies of 0.766 (7) and 0.234 (7) for one ring and 0.639 (10) and 0.361 (10) for the other. In the second phospho-ramide mol-ecule, one of the NC(4)H(8)O moieties is disordered over two sets of sites with site occupancies of 0.807 (6) and 0.193 (6). In the crystal, pairs of inter-molecular N-H?O(P) hydrogen bonds form two independent centrosymmetric dimers. PMID- 22091209 TI - Phenyl bis-(morpholin-4-yl-amido)-phosphinate. AB - In the title compound, C(14)H(23)N(4)O(4)P, the P atom is in a distorted tetra hedral environment with bond angles in the range 96.87 (6)-119.86 (6) degrees . The two morpholinyl groups adopt a chair conformation. The phenyl ring is disordered over two sets of sites with equal occupancies [0.500 (2)]. In the crystal, adjacent mol-ecules are linked via N-H?O hydrogen bonds into an extended chain running parallel to the a axis. Only one of the amidate N-H groups is involved in hydrogen bonding. PMID- 22091210 TI - (2RS,3SR,10SR,11RS)-3,10-Diphen-oxy-18,21-dioxa-5,8-diaza-penta-cyclo [20.4.0.0.0.0]hexa-cosa-1(26),12,14,16,22,24-hexa-ene-4,9-dione ethyl acetate hemisolvate. AB - In the title compound, C(34)H(30)N(2)O(6).0.5C(4)H(8)O(2), there are two mol ecules in the asymmetric unit and the structure is stabilized by C-H?O inter actions. The two nonsolvent mol-ecules of the asymmetric unit are linked together by a weak C-H?O hydrogen bond. The ethyl acetate mol-ecule is present as a space filler and does not participate in the hydrogen-bonding network. PMID- 22091211 TI - (E)-4-Bromo-N-(2-chloro-benzyl-idene)-aniline. AB - In the title Schiff base mol-ecule, C(13)H(9)BrClN, the dihedral angle between the benzene rings is 49.8 (2) degrees and the mol-ecule has an E configuration about the C=N bond. In the crystal, there are no directional interactions but only van der Waals inter-molecular inter-action forces between neighbouring mol ecules. PMID- 22091212 TI - 1,3-Diisopropyl-4,5-dimethyl-imidazolium benzene-sulfonate. AB - In the title salt, C(11)H(21)N(2) (+).C(6)H(5)O(3)S(-), which has two cation anion pairs in the asymmetric unit, the two imidazolium cations are linked to two separate acceptor O atoms of one of the benzene-sulfonate anions through aromatic C-H?O hydrogen bonds, while the second anion is unassociated. PMID- 22091213 TI - A monoclinic polymorph of (1E,5E)-1,5-bis-(2-hy-droxy-benzyl-idene)thio-carbono hydrazide. AB - The title compound, C(15)H(14)N(4)O(2)S, is a derivative of thio-ureadihydrazide. In contrast to the previously reported polymorph (ortho-rhom-bic, space group Pbca, Z = 8), the current study revealed monoclinic symmetry (space group P2(1)/n, Z = 4). The mol-ecule shows non-crystallographic C(2) as well as approximate C(s) symmetry. Intra-molecular bifurcated O-H?(N,S) hydrogen bonds, are present. In the crystal, inter-molecular N-H?S hydrogen bonds and C-H?pi contacts connect the mol-ecules into undulating chains along the b axis. The shortest centroid-centroid distance between two aromatic systems is 4.5285 (12) A. PMID- 22091214 TI - 1',3',4',5',7',8'-Hexafluoro-1,1'',2,2'',3,3'',4,4''-octa-phenyl-2',6'-dihydro dispiro-[cyclo-penta-1,3-diene-5,2'-naphthalene-6',5''-cyclo-penta-1'',3''-diene] dichloro-methane monosolvate. AB - The mol-ecule of the title compound, C(66)H(40)F(6).CH(2)Cl(2), is centrosymmetric; the dihedral angle between the central fluorinated unit and the cyclo-penta-diene ring is 88.36 (7) degrees . The dihedral angles between the cyclo-penta-diene ring and the four surrounding phenyl rings are in the range 26.6 (1)-65.6 (1) degrees . Centrosymmetric cavities in the crystal structure are populated by disordered dichloro-methane solvent mol-ecules. PMID- 22091215 TI - 4-Hy-droxy-3-[(E)-3-phenyl-prop-2-eno-yl]-2H-chromen-2-one. AB - In the title mol-ecule, C(18)H(12)O(4), the phenyl ring is twisted by 23.2 (1) degrees from the mean plane of the chromene system. In the crystal, weak inter molecular C-H?O hydrogen bonds link mol-ecules into zigzag chains extending in the [010] direction. An intra-molecular O-H?O hydrogen bond is also present. PMID- 22091216 TI - Climate change and consequences in the Arctic: perception of climate change by the Nenets people of Vaigach Island. AB - BACKGROUND: Arctic climate change is already having a significant impact on the environment, economic activity, and public health. For the northern peoples, traditions and cultural identity are closely related to the natural environment so any change will have consequences for society in several ways. METHODS: A questionnaire was given to the population on the Vaigach island, the Nenets who rely to a large degree on hunting, fishing and reindeer herding for survival. Semi-structured interviews were also conducted about perception of climate change. RESULTS: Climate change is observed and has already had an impact on daily life according to more than 50% of the respondents. The winter season is now colder and longer and the summer season colder and shorter. A decrease in standard of living was noticeable but few were planning to leave. CONCLUSION: Climate change has been noticed in the region and it has a negative impact on the standard of living for the Nenets. However, as of yet they do not want to leave as cultural identity is important for their overall well-being. PMID- 22091217 TI - The role of monocyte-lineage cells in human immunodeficiency virus persistence: mechanisms and progress. AB - Human immunodeficiency virus type 1 (HIV-1) persistence is a major barrier to the successful treatment and eradication of acquired immunodeficiency syndrome (AIDS). In addition to resting CD4(+) T cells, a significant long-lived compartment of HIV-1 infection in vivo includes blood monocytes and tissue macrophages. Studying HIV-1 persistence in monocyte-lineage cells is critical because these cells are important HIV-1 target cells in vivo. Monocyte-lineage cells, including monocytes, dendritic cells (DCs) and macrophages, play a significant role in HIV-1 infection and transmission. These cells have been implicated as viral reservoirs that facilitate HIV-1 latency and persistence. A better understanding of HIV-1 interactions with monocyte-lineage cells can potentially aid in the development of new approaches for intervention. This minireview highlights the latest advances in understanding the role of monocyte lineage cells in HIV-1 persistence and emphasizes new insights into the mechanisms underlying viral persistence. PMID- 22091218 TI - Successful implementation of a perioperative glycemic control protocol in cardiac surgery: barrier analysis and intervention using lean six sigma. AB - Although the evidence strongly supports perioperative glycemic control among cardiac surgical patients, there is scant literature to describe the practical application of such a protocol in the complex ICU environment. This paper describes the use of the Lean Six Sigma methodology to implement a perioperative insulin protocol in a cardiac surgical intensive care unit (CSICU) in a large academic hospital. A preintervention chart audit revealed that fewer than 10% of patients were admitted to the CSICU with glucose <200 mg/dL, prompting the initiation of the quality improvement project. Following protocol implementation, more than 90% of patients were admitted with a glucose <200 mg/dL. Key elements to success include barrier analysis and intervention, provider education, and broadening the project scope to address the intraoperative period. PMID- 22091219 TI - Legumes: A component of a healthy diet. PMID- 22091220 TI - Relationship between gamma-glutamyl transferase and glucose intolerance in first degree relatives of type 2 diabetics patients. AB - BACKGROUND: Considering that serum gamma-glutamyl transferase (GGT) activity could reflect several different processes relevant to diabetes pathogenesis and the increasing rate of type 2 diabetes worldwide, the aim of this study was to assess the association between serum GGT concentrations and glucose intolerance, in the first-degree relatives (FDR) of type 2 diabetic patients. METHODS: In this descriptive study, 30-80 years old, non diabetic FDRs of type 2 diabetic patients were studied. Serum GGT was measured by enzymatic photometry method in all studied population. The relationship between GGT and glucose intolerance status (normal, prediabetic and diabetics) was evaluated. RESULTS: During this study 551 non-diabetic FDRs of type 2 diabetic patients were studied. Mean of GGT was 25.3 +/- 12.1 IU/L. According to glucose tolerance test, 153 were normal and 217 and 181 were diabetic and prediabetic respectively. Mean of GGT in normal, prediabetic and diabetic patients was 23.5 +/- 15.9 IU/L, 29.1 +/- 28.1 IU/L and 30.9 +/- 24.8 IU/L respectively (p = 0.000). The proportion of prediabetic and diabetic patients was higher in higher quartile of GGT and there was a significant correlation between GGT and BMI, HbA1c, FPG, cholesterol, LDL-C, and triglyceride (p < 0.05). There was a significant relation between GGT and area under the curve (AUC) of oral glucose tolerance test (p = 0.00). CONCLUSIONS: Measurement of GGT in FDRs of type 2 diabetic patients may be useful in assessing the risk of diabetes; those with chronically high levels of GGT should be considered as high risk group for diabetes. PMID- 22091221 TI - Change in functional bowel symptoms after prostatectomy: a case-control study. AB - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that up to 20% of the population is suffering from it. Also benign prostatic hyperplasia (BPH) is a common problem that approximately 90 percent of men may be affected by this condition until the eighth decade of their life. Prostatectomy as a surgery and pelvic intervention can cause IBS. METHODS: It was a case control study including 66 patients in 2 case groups and 66 patients in 2 control groups. Case groups were patients who underwent open prostatectomy and transurethral resection of the prostate (TURP) and control groups were patients who were candidate for prostatectomy. RESULTS: Ten patients in case groups and five patients in control groups had IBS. There was no significant difference in IBS between control and case groups (p = 0.117). CONCLUSIONS: This is the first forward study regarding bowel symptom changes following prostatectomy. The main positive finding of this study is that open prostatectomy was followed by significant increase in diarrhea and bowel habit alternation associated with onset of abdominal pain. Specifically the change was found after open operation but not after TURP. Prostatectomy whether in form of open or transurethral may cause onset of abdominal discomfort and bowel habit change. PMID- 22091222 TI - Detection and classification of cardiac ischemia using vectorcardiogram signal via neural network. AB - BACKGROUND: Various techniques are used in diagnosing cardiac diseases. The electrocardiogram is one of these tools in common use. In this study vectorcardiogram (VCG) signals are used as a tool for detection of cardiac ischemia. METHODS: VCG signals used in this study were obtained form 60 patients suspected to have ischemia disease and 10 normal candidates. Verification of the ischemia had done by the cardiologist during strain test by the evaluation of electrocardiogram (ECG) records and patient's clinical history. The recorder device was Cardiax digital recorder system. The VCG signals were recorded in Frank lead configuration system. RESULTS: Extracted ischemia VCG signals have been configured with 22 features. Feature dimensionalities were reduced by the use of Independent Components Analysis and Principal Component Analysis tools. Results obtained from strain test indicated that among 60 subjects, 50 had negative results and 10 had positive results. Ischemia detection of neural network using VCG parameters indicates 86% accuracy. Classification result on neural network using ECG ischemia detection parameters is 73% accurate. Accumulative evaluation including VCG analysis and strain test indicates 90% consistency. CONCLUSIONS: Regarding the obtained results in this study, VCG has higher accuracy than ECG, so that in cases which ECG signal cannot provide certain diagnosis of existence or non-existence of ischemia, VCG signal can help in a wider range. We suggest the use of VCG as an auxiliary low cost tool in ischemia detection. PMID- 22091223 TI - Relationship between serum N-terminal Pro Brain Natriuretic Peptide (NT-Pro BNP) level and the severity of coronary artery involvements. AB - BACKGROUND: Rapid measuring of B-type natriuretic peptide (BNP) in the emergency departments effectively results in evaluating patients with acute cardiac attacks and has appeared to be a useful prognostic marker of cardiovascular risk. A current study came to address the association between plasma N-terminal pro BNP level and severity of coronary vessels' defects based on Gensini score in patients with stable angina pectoris candidate for coronary angiography. METHODS: The study population consisted of 92 consecutive patients with appearance of stable angina and candidate for coronary angiography. All participants underwent selective left and right coronary angiography. For BNP measurement and just before the catheterization of left coronary, 5cc blood samples were drawn from coronary. RESULTS: With respect to the role of N terminal pro BNP for predicting severity of CAD based on Gensini scoring, linear regression analysis confirmed that plasma BNP level was a strong predictor for CAD severity (p = 0.009) in the presence of study cofounders. A significant correlation was also observed between N terminal pro BNP and left ventricular ejection fraction, so that all patients with left ventricular dysfunction (EF < 40%) had plasma N terminal pro BNP level higher than 100 pg/ml. CONCLUSIONS: NT-pro BNP can be a good parameter for predicting the severity of coronary vessels' involvement besides other diagnostic tools. In all patients with left ventricular ejection fraction less than 40%, plasma NT-pro BNP level was higher than 100 pg/ml. PMID- 22091224 TI - High dose Senna or Poly Ethylene Glycol (PEG) for elective colonoscopy preparation: a prospective randomized investigator-blinded clinical trial. AB - BACKGROUND: The aim of this study was to determine the efficacy of two methods of colon preparation for colon cleansing in a randomized controlled trial. METHODS: In this prospective randomized investigator-blinded trial, consecutive outpatients indicated for elective colonoscopy were randomized into two groups. Patients in Senna group took 24 tablets of 11 mg Senna in two divided doses 24 hour before colonoscopy. In Poly Ethylene Glycol (PEG) group they solved 4 sachets in 4 liters of water the day before the procedure and were asked to drink 250 ml every 15 minutes. The overall quality of colon cleansing was evaluated using the Aronchick scoring scale. Difficulty of the procedure, patients' tolerance and compliance and adverse events were also evaluated. RESULTS: 322 patients were enrolled in the study. There was no significant difference in the quality of colon cleansing, patients' tolerance, compliance and the difficulty of the procedure between two groups (p > 0.05). The incidence of adverse effects was similar between two groups except for abdominal pain that was more severe in Senna group (p < 0.05) and nausea and vomiting that was more common in PEG group (p < 0.05) CONCLUSIONS: In conclusion we deduce that Senna has the same efficacy and patient's acceptance as Polyethylene glycol-electrolyte solution (PEG-ES) and it could be prescribed as an alternative method for bowel preparation. PMID- 22091225 TI - The association of hypertriglyceridemic waist phenotype with type 2 diabetes mellitus among individuals with first relative history of diabetes. AB - BACKGROUND: Antropometric measures with biochemical indicators have been used as screening tools for metabolic abnormalities in adolescents and adults. A few studies have assessed the relation of EWET (Enlarge waist Elevated triglyceride) phenotype with diabetes, especially among individuals with first relative history of diabetes. This study aimed to evaluate the association of EWET phenotype with diabetes among individuals with family history of diabetes. METHODS: Antropometric and biochemical measurments were evaluated in a population - based cross - sectional study of 332 male and 991 female Isfahani adults aged 35-55 year. The EWET phenotype was defined as serum trigcylglycerol concentrations >= 150 mg/dl and concurrent waist circumference (WC) >= 88 cm in females and >= 102 cm in males. RESULTS: The prevalence of EWET phenotype was respectively 9.6% and 23.6% among male and female. Individuals with the phenotype had significantly higher BMI and WHR (waist to hip ratio) as compared to other groups. After control for age and physical activity, male with EWET phenotype were significantly more likely to have high serum triglyceride levels (p < 0.001), cholesterol (p < 0.001). Even after additional control for BMI, the significant associations remained except for low HDL Cholestrol. Female with EWET phenotype had significantly adverse metabolic risks as compared to other groups, either before or after control for BMI (p < 0.001). Individuals with the phenotype were more likely to have diabetes (both gender) and (IGT) Impaired Glucose Tolerance (female only). CONCLUSIONS: Our results showed that EWET phenotype has significantly associated with diabetes. This phenotype could be used for early identification of diabetes and IGT. PMID- 22091226 TI - The effect of Ramadan fasting on fetal growth and Doppler indices of pregnancy. AB - BACKGROUND: The aim of this study was to determine the effect of Ramadan fasting on fetal growth and Doppler in-dices of pregnancy. METHODS: Fifty two healthy pregnant women of second or third trimester, 25 in fasting group and 27 in non fasting group were included. Growth parameters including biparietal diameter (BPD), femoral length (FL), abdominal circumference (AC), estimated fetal weight, amniotic fluid index and also Doppler indices of both uterine and umbilical arteries (including peak systolic and end diastolic velocity, systolic to diastolic ratio, resistive and pulsatility indices) were evaluated by Gray scale and colour Doppler imaging for each women two times, in the beginning and at the end of Ramadan. RESULTS: Increases in BPD, FL, AC and fetal weight within one month were similar in two groups. Amniotic fluid index also were similar in two groups. There was not any statistically significant difference in abnormal Doppler indices of uterine or umbilical artery between two groups. CONCLUSIONS: The results of present study show that Ramadan fasting has no adverse effect on fetal growth, amniotic fluid volume or maternofetal circulation. PMID- 22091227 TI - IGF-I concentration and changes in critically ill patients. AB - BACKGROUND: Insulin-like growth factor 1 (IGF-I) is an anabolic growth factor that affects nitrogen balance and its changing trend is not clearly understood in critically ill patients. This study was carried out to evaluate the association between serum IGF-I levels and its changing trend in critically ill patients. METHODS: In this nested case-control study, all consecutive patients admitted to the medical ICU of Rasoul-e-Akram and Firuzgar hospital (Tehran, Iran) from January through October 2008 were included. IGF1 concentration was measured within the first 24h of ICU admission and the fourth, seventh and tenth day since admission. Patients were followed until discharge from ICU or expiration. RESULTS: The study population consisted of 90 patients (mean age: 58.01 +/- 22.56), 31 (34.4%) of who died and 59 (65.6%) were discharged. On admission, 43 patients (47.7%) had low IGF-I levels, whereas 47 (52.3%) had normal or high levels. The concentration of IGF-I was not significantly different in every 4 measurements between expired and discharged patients. Significant decrease was seen between first to fourth day IGF-I concentration (p = 0.005). Changing trend was not statistically different in two groups of patients. CONCLUSIONS: There was no relation between low IGF-I concentration on admission day and increased adverse outcome, but overall these patients had lower IGF1. No clear association was found between changing trend of IGF1 and mortality. Stress on admission time may cause decreasing pattern of IGF-I in the first 4 days of admission. PMID- 22091228 TI - Evaluation of hearing loss in juvenile insulin dependent patients with diabetes mellitus. AB - BACKGROUND: Diabetes mellitus is one of the most important epidemics of our era. Complications of this disease are diverse and include retinopathy, nephropathy and neuropathy. This study has been designed to evaluate hearing loss patterns in young children suffering from IDDM and define risk factors for this complication. METHODS: This descriptive analytic study includes 200 youngsters divided into two groups: 100 patients in diabetic group and 100 healthy individual in control group. Hearing thresholds are determined in 250, 500, 1000, 2000, 4000 and 8000 Hz and metabolic controls are evaluated as average of one year HbA1C, dividing diabetic group into well control and poor control subgroups. RESULTS: Twenty one out of 100 patients in diabetic group showed significant hearing loss. Hearing loss is correlated with metabolic control, showing less loss in patients with HbA1C less than 7.5%. Results showed that hearing loss is not related to sex of patients but duration of disease (more or less than 5 years) affects degree of hearing loss in some frequencies. CONCLUSIONS: Hearing loss in children suffering from IDDM is sensorineural, bilateral and symmetrical and is related to the duration of disease and state of metabolic control (HbA1C). PMID- 22091229 TI - Helicobacter pylori as a zoonotic infection: the detection of H. pylori antigens in the milk and faeces of cows. AB - BACKGROUND: The prevalence of Helicobacter pylori infection, which may increase the risk of gastritis, peptic ulcers, and cancer, has increased worldwide. This number is estimated to be around 70-90% in developing countries and 25-50% in developed countries. It is possible that the bacterium can be transmitted via food and water as well as zoonotically and iatrogenically. Because of high prevalence of this infection in Iran, the aim of this study is to examine whether H. pylori infection might be transmitted from cow's milk and faeces. METHODS: The existence of the H. pylori antibody and antigen was investigated in samples of serum, milk, and faeces from 92 lactating Holstein cows in Shahrekord, Iran. The H. pylori antigen and antibody were detected using ELISA and were confirmed by PCR. RESULTS: It was found that out of 92 serum specimens, 25 (27%) of the cows were positive for the H. pylori antibody and 67 specimens were negative. From these 25 seropositive cows, 10 (40%) faeces samples and four (16%) milk samples were antigen positive for H. pylori. Four of the antigen-positive milk specimens were also antigen positive for faeces. The existence of the UreC gene was also confirmed in positive samples of milk and faeces. CONCLUSIONS: There is a possibility that cow's milk is a transmission mode in H. pylori infection and faecal contamination and inappropriate management processes could transfer H. pylori to humans. The awareness of the H. pylori epidemiology and its method of distribution are necessary for public health measures and controlling the spread of this bacterium. Further investigation with a greater sample number is necessary to verify the ability of H. pylori transmission via milk consumption. PMID- 22091230 TI - The effects of hypotension on differences between the results of simultaneous venous and arterial blood gas analysis. AB - BACKGROUND: Analysis of venous blood gas (VBG) can represent arterial blood gas (ABG) analysis in patients with various diseases. The effects of hypotension on differences between the results of simultaneous venous and arterial blood gas analyses were reviewed. METHODS: This observational, cross-sectional study was conducted from March to October 2010 in emergency departments of two university hospitals in Tehran (Iran) on consecutive adult patients for whom ABG had been indicated for diagnosis/treatment. Arterial and peripheral venous bloods were simultaneously sampled with blood pressure measurement. The VBG-ABG amount of difference regarding pH, HCO(3), PCO(2), PO(2), SO(2), and Base Excess (BE) was compared between those with and without hypotension. RESULTS: During the study, 192 patients (51.6 +/- 23.6 years, 67.7% males) were entered into the hypotension (n = 78) and normotensive groups (n = 114). The average VBG-ABG amount of difference (95% limits of agreement) in the hypotension versus normotensive group were -0.030 (-0.09 to 0.03) vs. -0.016 (-0.1 to 0.068) for pH (p = 0.01), 1.79 ( 1.91 to 5.49) vs. 1.32 (-1.94 to 4.58) mEq/L for HCO(3) (p = 0.032), 2.69 (-20.43 to 25.81) vs. 2.03 (-7.75 to 11.81) mmHg for PCO(2) (p = 0.295), -35.97 (-130.17 to 58.23) vs. -32.65 (-104.79 to 39.49) mmHg for PO(2) (p = 0.293), -18.58 ( 14.66 to 51.82) vs. -9.06 (-31.28 to 13.16) percent (p < 0.001) for SO(2), and 0.25 (-3.73 to 4.23) vs. 0.79 (-2.51 to 4.09) for BE (p = 0.036). CONCLUSIONS: Hypotensive status is associated with an increase in the amount of difference between VBG and ABG analysis regarding pH, HCO(3), and BE, though the amount of increase does not seem to be clinically important. Studying the precise effects of replacing ABG with VBG on the clinical decision-making and the following outcomes is worth-while. PMID- 22091231 TI - Effects of health belief model-based video training about risk factors on knowledge and attitude of myocardial infarction patients after discharge. AB - BACKGROUND: Ischemic heart diseases are the most common cardiovascular diseases. This study aimed to assess the effects of video training about risk factors based on health belief model on knowledge and attitude of myocardial infarction patients after discharge. METHODS: This was a quasi-experimental study conducted in 2010. Eighty patients were randomly assigned to either intervention or control group. Data was collected by a researcher-made questionnaire. RESULTS: Study results showed that the mean score of knowledge about disease, diet, physical activity and perceived benefit, severity, and susceptibility after video training was increased significantly. CONCLUSIONS: Using videos for educating myocardial infarction patients is a useful method for preventing recurrence of the disease. PMID- 22091233 TI - Bacterial meningitis: a new risk factor. AB - BACKGROUND: The purpose of this study is to discuss a possible new risk factor for the bacterial meningitis. METHODS: Cerebrospinal fluid collected from 270 patients was assayed. An enzyme immunosorbent assay for the detection of Staphylococcal enterotoxins A to E was used. RESULTS: The results indicated that the frequency of Coagulase Negative Staphylococci (CoNS) was 35 (20.46%). An important finding of this research was that the CoNS isolates produced enterotoxin C and D or enterotoxin C and E. CONCLUSIONS: This is the first report of enterotoxin-producing Coagulase Negative Staphylococci isolated from CSF patients. Therefore, these enterotoxins probably act as risk factors in the bacterial invasion into central nervous system. PMID- 22091232 TI - Irritable bowel syndrome in adults over 35 years in Shiraz, southern Iran: prevalence and associated factors. AB - BACKGROUND: The symptoms of irritable bowel syndrome (IBS) are common in the general population. The aim of this population-based study was to determine the prevalence of IBS and describe the associated factors including demographic, life style and health-seeking behaviors in Shiraz city, southern Iran. METHODS: From April to September 2004, 1978 subjects aged > 35 years old completed a validated and reliable questionnaire on IBS. RESULTS: The prevalence rate of IBS was 10.9%, higher in females, in 35-44 years old age group and among subjects eating fast food (14.1%) but was lower in those taking more fruits and vegetables (10.5%). The occurrence of anxiety, nightmare and restlessness was also significantly higher in subjects with IBS. It had an association with psychological distress and recurrent headaches but not with drinking tea/coffee, smoking or physical activity. CONCLUSIONS: In our area, IBS was correlated with gender, age, psychological distress, recurrent headaches and consumption of fast foods that necessitate health planning programs by health policy makers. PMID- 22091234 TI - Physician's acquittal of responsibility in Iranian statutes. AB - The physician's acquittal has obsessed Iranian legislator's mind to a large extent. This is exclusively observed in Iranian statuses and specifically in Shi'ite school of though. Muslim jurists' opinions play a very important role in enacting legal articles related to it. After reviewing the literature, the authors tried to pick and collect common features of physician's responsibilities and duties to introduce Iranian Acts with respect to the subject. Also, Iranian Acts are analyzed and the challenging medical topics such as emergency situations and infectious diseases are discussed.Iranian legislator didn't specify a kind of physician's acquittal which received from the patient knowingly and is based on his/her free will. There are also some medical and legal gaps. Patients are not often informed of all exact and scientific information and results of their treatments. Furthermore, the forms prepared to receive the patient's consent do not provide what Iranian legislator meant. PMID- 22091235 TI - A pulmonary aspergillosis case with fatal course in a patient with SIRS clinic. AB - A 77-year-old male patient with a history of tuberculosis applied to emergency service with complaints of confusion, shortness of breath, tachycardia, hypothermia and hypotension. A bronchoalveolar lavage culture was collected because a fungus ball was seen on repeat chest X-ray and thoracic CT of the patient. Aspergillus fumigatus grew and voricona-zole treatment was started, but the patient was lost from multiple organ failure (MOF). In diagnosis of patients with SIRS clinic, causative factor may be aspergillus located in an old tuberculosis cavity, and this may have a fatal course in an old patient having previous pulmonary and systemic diseases. PMID- 22091236 TI - A case report of cemento-ossifying fibroma presenting as a mass of the ethmoid sinus. AB - Cemento-ossifying fibroma is a lesion containing both fibrous and osseous components. Such lesions include fibrous dysplasia, ossifying fibroma, cemento ossifying fibroma and cementifying fibroma. Periodontal membrane is the origin of fibro-osseous lesions other than fibrous dysplasia.Here a clinical case of a young woman referred for evaluation of a mass in the right side of face between eye and nose is presented. The first time she noticed the mass was 2 years ago and was growing larger inwards. She was treated with surgical resection.In this case of a cemento-ossifying fibroma, histological interpretation was critical, and was the basis of correct treatment. PMID- 22091237 TI - Myasthenia gravis as a presenting feature in a patient with lung cancer: A case report. AB - A male patient with muscle weakness had clinical findings of ptosis, diplopia, proximal leg weakness, and positive repetitive nerve stimulation (RNS) test. He demonstrated positive acetylcholine receptor antibody. This lung cancer patient was presenting myasthenia gravis. The causal association between non-small-cell lung cancer and non-thymomatous myasthenia gravis has not been clarified yet. To date, there has been no evidence supporting the speculation that association of myasthenia gravis with lung cancer might be one of the phenotypes of paraneoplastic syndrome. PMID- 22091238 TI - Fracture of ossified Achilles tendon. PMID- 22091239 TI - Comparison of Generalized Estimating Equations and Quadratic Inference Functions in superior versus inferior Ahmed Glaucoma Valve implantation. AB - BACKGROUND: The celebrated generalized estimating equations (GEE) approach is often used in longitudinal data analysis While this method behaves robustly against misspecification of the working correlation structure, it has some limitations on efficacy of estimators, goodness-of-fit tests and model selection criteria The quadratic inference functions (QIF) is a new statistical methodology that overcomes these limitations. METHODS: We administered the use of QIF and GEE in comparing the superior and inferior Ahmed glaucoma valve (AGV) implantation, while our focus was on the efficiency of estimation and using model selection criteria, we compared the effect of implant location on intraocular pressure (IOP) in refractory glaucoma patients We modeled the relationship between IOP and implant location, patient's sex and age, best corrected visual acuity, history of cataract surgery, preoperative IOP and months after surgery with assuming unstructured working correlation. RESULTS: 63 eyes of 63 patients were included in this study, 28 eyes in inferior group and 35 eyes in superior group The GEE analysis revealed that preoperative IOP has a significant effect on IOP (p = 0 011) However, QIF showed that preoperative IOP, months after surgery and squared months are significantly associated with IOP after surgery (p < 0 05) Overall, estimates from QIF are more efficient than GEE (RE = 1 272). CONCLUSIONS: In the case of unstructured working correlation, the QIF is more efficient than GEE There were no considerable difference between these locations, our results confirmed previously published works which mentioned it is better that glaucoma patients undergo superior AGV implantation. PMID- 22091240 TI - Acute and long term effects of grape and pomegranate juice consumption on endothelial dysfunction in pediatric metabolic syndrome. AB - BACKGROUND: This study aimed to determine the short- and long-term effects of consumption of grape and pomegranate juices on markers of endothelial function and inflammation in adolescents with metabolic syndrome (MetS). METHODS: In a non pharmacologic randomized controlled trial, 30 individuals were randomly assigned to two groups of drinking natural grape or pomegranate juice for 1 month. Measurements of inflammatory factors [Hs-CRP, sE-selectin, sICAM-1, sVCAM, and interleukin 6 (IL-6)] and flow-mediated dilation (FMD) were made at baseline, 4 hours after first juice consumption and after one month of juice consumption. RESULTS: The percent changes of FMD were significant in both groups in the short- and long-term. Hs-CRP had a nonsignificant decrease. sE selectin had a significant decrease after 4 hours in total and in the pomegranate juice group, followed by a significant decrease after 1 month in both groups. After 4 hours, sICAM-1 significantly decreased in the pomegranate juice group, and after 1 month it decreased in total and pomegranate juice group. Interleulkin-6 (IL-6) had a significant constant decrease at 4-hour and 1-month measurements after drinking pomegranate juice, and in both groups after 1 month. Significant negative correlations of changes in sICAM-1 and sE-selectin with changes in FMD were found in both periods of follow-up; and at 1 month for IL-6. CONCLUSIONS: Decline in inflammation was associated with improvement in FMD without changes in conventional risk factors. Daily consumption of natural antioxidants may improve endothelial function in adolescents with MetS. PMID- 22091241 TI - Metabolic syndrome and health-related quality of life in Iranian population. AB - BACKGROUND: To investigate the association between Metabolic syndrome (MetS) and Health related quality of life (QoL) in Iranian population. METHODS: We used data from the post-intervention phase of Isfahan Healthy Heart Program (IHHP), a community trial for cardiovascular disease (CVD) prevention and control. We recruited 9570 healthy adults, aged >= 19 years who were randomly selected using multistage random sampling method. World Health Organization QoL questionnaire (WHOQOL-BREF) which contains 26 items was used to assess QoL. It assesses four domains of QoL; Physical health, Psychological health, Social relationship and Environmental issues. MetS was defined based on ATP III criteria. RESULTS: The mean age of participants was 38.8+/-15.6 years (mean +/- SD) and the prevalence of MetS was 22.5%. From all participant 18.2% were illiterate and 13.2% had university educational level. Two way multivariate analyses of covariance (MANCOVA) test after adjusting age showed significant difference between women with and without Mets in regard to physical health and social relations domains, while none of QoL domains was different in men with Mets in comparison to men without it. CONCLUSIONS: After adjusting the role of socio-demographic factors as components of QoL score, no association was observed between QoL domains and MetS in men, while only social relations and physical health scores were higher in women with Mets compared to those without Mets. Other variety of health-related QoL assessment tools or definitions of MetS may show different relationship in the Iranian socio-cultural context. PMID- 22091242 TI - A novel prediction model for all cause emergency department visits in ischemic heart disease. AB - BACKGROUND: Ischemic heart disease (IHD) is the main cause of morbidity and mortality worldwide, and a considerable part of these patients attend to emergency departments, which increases the burden to these busy departments. The aim of this study was to develop a prediction model enabling prediction of all cause emergency department (ED) visits in patients with documented coronary stenosis in a derivation set, and then to determine its accuracy in a validation set. METHODS: In a prospective study at outpatient setting of Baqiyatallah hospital, Tehran, Iran, 502 patients with IHD were followed for 6 months for observing the outcome of ED visits for all causes. They were divided in two random groups of derivation set (n = 335) and validation set (n = 167). In the derivation set, to achieve an all cause ED visits prediction model, a prediction model was reached by entering demographic data, clinical variables, somatic comorbidity (Ifudu index), level of anxiety and depression (Hospital Anxiety Depression Scale (HADS) questionnaire), and angina grade (WHO Rose Angina) to a logistic regression. Then in the validation set, the sensitivity, specificity, and the accuracy of that model was tested. RESULTS: A novel model for prediction of all cause ED visits in IHD patients in six months was presented with gender, anxiety, WHO angina grade and somatic comorbidity as inputs. Sensitivity, specificity, and accuracy of the model were 63.0%, 68.6%, and 67.7%, respectively. CONCLUSIONS: Testing and using the achieved model is suggested to health care providers in other settings. PMID- 22091243 TI - Coronary angiogenesis during experimental hypertension: is it reversible? AB - BACKGROUND: We investigated coronary angiogenesis and serum vascular endothelial growth factor (VEGF) and its soluble receptor-1 (sFlt-1) concentrations in two kidney one-clip (2K1C) hypertensive rats before and after reversal of hypertension. METHODS: THE ANIMAL GROUPS WERE: (i) sham-clipped for 12 weeks; (ii) 2K1C for 12 weeks; (iii) sham-clipped for 12 weeks and unclipped for 12 weeks; and (iv) 2K1C for 12 weeks and unclipped for 12 weeks. Blood samples were taken before experiments and after clipping and unclipping; capillary density was also evaluated. RESULTS: Our results showed that blood pressure in hypertensive animals was higher than sham group (175 +/- 10 vs. 110.3 +/- 11.3 mmHg; p < 0.05). Unclipping significantly reduced blood pressure in hypertensive rats (p < 0.05). Serum VEGF and sFlt-1 levels in hypertensive group were significantly lower than sham group (VEGF: 74.36 +/- 5.85 vs. 104.07 +/- 7.75 pg/ml; sFlt-1: 426.67 +/- 25.74 vs. 690.76 +/- 41.14 pg/ml, respectively; p < 0.05). Unclipping in hypertensive animals increased serum VEGF and sFlt-1 concentrations (VEGF: 93.65 +/- 8.61 vs. 74.36 +/- 5.85 pg/ml; sFlt-1: 742.05 +/- 79.23 vs. 426.67 +/- 25.74 pg/ml, respectively; p < 0.05). In hypertensive animals, capillary density in the heart was higher than sham group, non-significantly (p > 0.05) and after unclipping, it reached to sham group level. CONCLUSIONS: It seems that changes in capillary density and serum VEGF and sFlt-1 concentrations in renovascular hypertension are reversible by removing the cause of hypertension and it shows the importance of early diagnosis and treatment of hypertension in clinical condition. PMID- 22091244 TI - Timing of puberty in Iranian girls according to their living area: a national study. AB - BACKGROUND: This study aimed to compare the timing of puberty between various geographic locations and different ethnicities. METHODS: This national survey was conducted in 20 provinces in Iran. Healthy Iranian girls were selected from public schools using cluster random sampling. A total number of 30 clusters including 7493 girls, aged 6.0-20 years, were selected. In order to compare different areas, the national classification of the provinces based on climate, ethnicity, geographic locations, and socioeconomic variables were used. Accordingly, there are 11 regions in Iran. Analysis of variance was used to compare the mean ages of menarche, pubarche, and thelarche in different regions. RESULTS: Tehranian girls, with 11.99 +/- 1.35 years (mean +/- SD), had the lowest age of menarche which was statistically significantly. The second region with lowest age at menarche was Fars (12.40 +/- 1.27 years). The mean age at breast bud stage (B2) was significantly lower in Ghazvin-Zanjan region (8.97 +/- 1.45 years). In Fars region, the mean age at B2 stage of breast development (11.01 +/- 1.88 years) was higher than other regions except for Mazendran-Guilan and Tehran related cities. The mean age at public hair development at Tanner stage 2 (PH2) in Kordestan-Lorestan-Ilam region (10.70 +/- 1.23 years) was significantly higher than other regions. CONCLUSIONS: We found significant differences in the age of pubertal stages of girls living in various regions with different ethnicity and geographic characteristics. Considering the impact of pubertal age on general health, more studies should be done about the lifestyle and environmental factors affecting the onset of puberty. PMID- 22091245 TI - Evaluation of pre lumbar puncture position on post lumbar puncture headache. AB - BACKGROUND: The most common complication of lumbar puncture (LP) occurring in over thirty percent of patients is headache. The position after lumbar puncture, needle type and size, and volume of the extracted cerebrospinal fluid (CSF) have been evaluated as contributory factors in occurrence of post lumbar puncture headache (PLPH), but the position before lumbar puncture has not been evaluated. METHODS: The occurrence of post lumbar puncture headache was evaluated in 125 patients undergoing lumbar puncture, divided randomly into sitting and lateral decubitus groups in the following five days. Chi-square test was used for statistical analysis. RESULTS: Thirty eight patients (30.4%) reported headache after lumbar puncture in the two groups, and post lumbar puncture headache was significantly lower in the lateral decubitus position (p = 0.001). There was no significant difference between genders in the post lumbar puncture headache occurrence (p = 0.767). CONCLUSIONS: Lumbar puncture in sitting position could produce more post lumbar puncture headache in comparison with lateral decubitus position. PMID- 22091246 TI - Effects of silybum marianum on patients with chronic hepatitis C. AB - BACKGROUND: Silymarin derived from silybum marianum (milk thistle), a flowering member of the daisy family, may benefit liver function in people infected with the hepatitis C virus. The aims of this pilot study were to assess the efficacy and safety of silymarin on serum hepatitis C virus (HCV) RNA, serum aminotransferases (ALT, AST) levels, liver fibrosis and well-being in patients with chronic hepatitis C (CHC). METHODS: This prospective self-controlled trial study was conducted from March to September 2006 at Department of Gastroenterology, Isfahan University of Medical Sciences, Isfahan, Iran. 55 patients with HCV (10 female and 45 male) with a mean age of 31.8 +/- 6.4 years (10-67 years) were participated in the study. Patients received 24 weeks of silymarin (630 mg/day). Baseline virological biochemical, liver fibrosis (by a serum fibrosis markers, including YKL-40 and Hyaluronic acid), and SF-36 questionnaire were performed with biochemical tests repeated at the end of the treatment period. RESULTS: There was statistically difference in mean of ALT (108.7 +/- 86.6 vs 70.3 +/- 57.7) before and after the treatment (p < 0.001). The means of AST were 99.4 +/- 139.7 and 59.7 +/- 64.32 before and after the treatment with statistically differences (p = 0.004). After the treatment, nine patients were found with negative HCV-RNA (p = 0.004) and statistically significant improvement in results of liver fibrosis markers were found only in fibrosis group (p = 0.015). Quality of life was improved significantly (p < 0.001). CONCLUSIONS: This study indicated that in patients with CHC performing silymarin (650 mg/day) for 6 months, improved serum HCV-RNA titer, serum aminotransferases (ALT, AST), hepatic fibrosis and patient's quality of life. More future studies are warranted. PMID- 22091247 TI - Genotyping of peroxisome proliferator-activated receptor gamma (PPAR-gamma) polymorphism (Pro12Ala) in Iranian population. AB - BACKGROUND: The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor. It is predominantly expressed in adipose tissue and as a receptor for thiazolidinediones, it has drawn attentions towards itself as a key molecule to trigger pathways involving in some diseases such as cancers, type 2 diabetes, inflammations and osteoporosis. A proline changed to alanine in codon 12 of PPAR-gamma gene (Pro12Ala) has been known to be responsible for decreased risk of type 2 diabetes. The aim of the present study is to investigate the frequency of Pro12Ala polymorphism in PPAR-gamma in healthy Iranian population to compare with other populations. Understanding this polymorphism may help us in better diagnosis, prevention, and therapeutic approaches toward a better management of diseases such as type 2 diabetes and osteoporosis. METHODS: 128 healthy volunteers were enrolled in this study. To determine single nucleotide polymorphisms (SNPs), we did real time polymerase chain reaction (RT-PCR), using TaqMan allelic discrimination assays. RESULTS: Genotype frequencies for PPAR gamma gene Pro12Ala (rs1801282) polymorphism were 0.86 for CC, 0.14 for CG, 0.00 for GG while allelic frequencies were 0.93 and 0.0.07 for C and G, respectively. CONCLUSIONS: There are statistical differences between the distribution of the PPAR-gamma-2 Pro12Ala polymorphism in other populations and Iranian population. PMID- 22091248 TI - Effect of soy phytoestrogen on metabolic and hormonal disturbance of women with polycystic ovary syndrome. AB - BACKGROUND: Phytoestrogens are a group of plants derived compounds with weekly estrogen effect that appear to have protective effects on metabolic and hormonal abnormalities of women with polycystic ovary syndrome (PCOS). So the aim of this study was to investigate the effect of soy phytoestrogens on reproductive hormones and lipid profiles in PCOS women. METHODS: In this quasi-randomized trial, 146 subjects with PCOS were divided into two groups; the experimental group who received Genistein (Bergamon, Italy) 18 mg twice a day orally and the control group that received similar capsules with cellulose for 3 months. Hormonal features and lipid profiles were measured before and after 3 months of supplement therapy. RESULTS: After 3 months of supplement therapy there were no statistically significant differences in high density lipoprotein cholesterol (HDL) and follicle stimulating hormone (FSH) serum levels in Genistein and placebo group before and after treatment; however serum levels of luteinizing hormone (LH), triglyceride (TG), low density lipoprotein cholesterol (LDL), dehydroepiandrostrone sulfate (DHEAS) and testosterone were significantly decreased after 3 months therapy in Genistein group. CONCLUSIONS: Genistein consumption may prevent cardiovascular and metabolic disorders in PCOS patients by improving their reproductive hormonal and lipid profiles. PMID- 22091249 TI - Successful prevention of tunneled, central catheter infection by antibiotic lock therapy using cefotaxime. AB - BACKGROUND: Chronic hemodialysis patients frequently require vascular access through central venous catheters (CVCs). The most significant complication of these catheters is infection. This risk can be lowered by the use of an antibiotic-Heparin lock. This study focuses on hemodialysis patients using Tunneled-cuffed catheters (TCC), to assess the rate of catheter-related infections (CRI) in catheter-restricted filling with Cefotaxime and Heparin in end stage renal disease patients. METHODS: A double-blind randomized study was conducted to compare 5000 U/ml Heparin plus10 mg/ml cefotaxime (CE/HS) as catheter-lock solutions, with Heparin (5000 U/ml) alone. A total of 30 patients with end-stage renal disease and different etiologies, were enrolled for chronic hemodialysis with permanent catheters from December 2009 to March 2010. These patients were randomly assigned to two groups of 15 members. Blood samples were collected for culture, sensitivity, and colony count, from the catheter lumen and the peripheral vein. CRI was considered as the end point. RESULTS: The rate of CRI was significantly lower in the cefotaxime group versus control group (p < 0.001). No exit site infection was occurred in both groups. Infection-free survival rates at 180 days were 100% for the CE/HS group, and 56% for the HS group. CONCLUSIONS: Antibiotic lock therapy using cefotaxime reduces the risk of CRI in hemodialysis patients. PMID- 22091250 TI - Situation analysis of local ethical committees in medical sciences in Iran. AB - BACKGROUND: Local ethical committees in medical sciences in Iran were established in 1999 in order to assess and evaluate the observance of ethical standards throughout the universities and research centers. The purpose of this study is to analyze the situation of local ethical committees in order to develop research ethics guideline. METHODS: For this cross-sectional study which has been conducted with the support of WHO, 40 local ethical committees in all universities of medical sciences were evaluated by use of determined questionnaires. RESULTS: In this study, 40 universities of medical sciences participated; all of them have established local ethical committees. Each committee has 5 to 11 members and in more than 80% cases, written guidelines for selecting the committee's members are available. The minimum number of members for official session is at least 3 and replacement of absent members, did not take place in more than 85% of the committees. Informed consent in 95% of these local ethical committees is available. In all committees, researches regarding the use of human subjects are under ethical consideration. In half of the local ethical committees, penalties for non-compliance with the regulations are considered. The average number of research project evaluated in last session of these committees was 15.2 and the committees in 50% of cases have provided ethics training specifically for their members. CONCLUSIONS: Policymakers should develop a standard guideline for local ethical committees in medical science universities in Iran. PMID- 22091251 TI - Evaluation of breast self-examination program using Health Belief Model in female students. AB - BACKGROUND: Breast cancer has been considered as a major health problem in females, because of its high incidence in recent years. Due to the role of breast self-examination (BSE) in early diagnosis and prevention of morbidity and mortality rate of breast cancer, promoting student knowledge, capabilities and attitude are required in this regard. This study was conducted to evaluation BSE education in female University students using Health Belief Model. METHODS: In this semi-experimental study, 243 female students were selected using multi-stage randomized sampling in 2008. The data were collected by validated and reliable questionnaire (43 questions) before intervention and one week after intervention. The intervention program was consisted of one educational session lasting 120 minutes by lecturing and showing a film based on HBM constructs. The obtained data were analyzed by SPSS (version11.5) using statistical paired t-test and ANOVA at the significant level of alpha = 0.05. RESULTS: 243 female students aged 20.6 +/- 2.8 years old were studied. Implementing the educational program resulted in increased knowledge and HBM (perceived susceptibility, severity, benefit and barrier) scores in the students (p <= 0.01). Significant increases were also observed in knowledge and perceived benefit after the educational program (p <= 0.05). ANOVA statistical test showed significant difference in perceived benefit score in students of different universities (p = 0.05). CONCLUSIONS: Due to the positive effects of education on increasing knowledge and attitude of university students about BSE, the efficacy of the HBM in BSE education for female students was confirmed. PMID- 22091252 TI - Comparative study of two anesthesia methods according to postoperative complications and one month mortality rate in the candidates of hip surgery. AB - BACKGROUND: Surgery for hip fractures can be done under general or neuraxial anesthesia. This study aimed to compare these two methods concerning their postoperative complications, duration of operation, hospitalization and the mortality rate within a period of one month after surgery. METHODS: 400 patients aged more than 30 years old and scheduled for elective operative fixation of fractured hip, randomly enrolled in two equal groups of general (GA) and neuraxial (NA) anesthesia. Hemoglobin level was measured before and 6 hours, 2, 3 and 5 days after the surgery. The intra and postoperative blood loss, duration of surgery, the severity of pain at the time of discharge from recovery and at the 2(nd), 3(rd) and 5(th) postoperative days were recorded. Statistical analysis was performed using SPSS version 12.0 by Mann-Whitney, chi-square, and t tests. P < 0.05 was considered significant. RESULTS: Both groups were similar regarding age, weight, and gender ratio. There was no significant difference in baseline hemoglobin, duration of surgery, length of hospitalization before surgery and the type of surgery. The mean of intraoperative blood loss and visual analogue score (VAS) in recovery and at the 3(rd) postoperative day, and also the length of hospitalization after surgery were significantly less in neuraxial anesthesia group. Both groups showed a significant decrease in hemoglobin values on the 2(nd) and 3(rd) postoperative days comparing to the baseline (p < 0.001). CONCLUSIONS: The morbidity and mortality rates of patients undergoing hip surgery were similar in both methods of anesthesia, but postoperative pain, blood loss, and duration of hospitalization were more in patients undergoing general anesthesia. PMID- 22091253 TI - An alternative management procedure after inadvertent dural puncture. AB - BACKGROUND: Accidental dural puncture during epidural blockade is a rare complication. Since postdural puncture headache (PDPH) is the most frequent complication, a wisely management method will also reduce the incidence of PDPH. METHODS: Five patients who had inadvertent dural puncture during the epidural procedure before hip or knee arthroplasty were included in this study. After dural puncture we drew back the epidural needle and placed an epidural catheter into the epidural space. RESULTS: Epidural anesthesia and postoperative epidural analgesia have been provided successfully in all cases. 20% showed PDPH. CONCLUSIONS: These results demonstrate the effectiveness of management skills after inadvertent dural punctures. PMID- 22091254 TI - Obesity predictors in people with chronic spinal cord injury: an analysis by injury related variables. AB - BACKGROUND: Despite an elevated obesity risk in people with spinal cord injury (SCI), investigation on the effects of age, obesity predictors, and injury related factors is yet to be unknown within the SCI population. METHODS: Obesity predictors were measured in 162 patients. RESULTS: 27.5% of the participants were overweight and 5.6% of them were obese. Mean BMI was different between patients with tetraplegia and paraplegia (p < 0.01). More than 20% of participants had central obesity, significantly patients with higher age and time since injury. CONCLUSIONS: Significant positive relationship was found between level of injury and BMI. Participants with higher age and time since injury had higher waist circumference. PMID- 22091256 TI - Intervention in the learning process of second year medical students. AB - BACKGROUND: It has been demonstrated that educational programs that focus on study skills could improve learning strategies and academic success of university students. Due to the important role of such supportive programs aimed at the fresh students, this survey was carried out to investigate the effectiveness of an optional course of learning and study skills on learning and study skills of second year medical students. METHODS: This quasi-experimental research was performed on 32 eligible medical students in Isfahan University of Medical Sciences, who chose the optional course of learning and study skills. Both of intervention and control groups completed Learning and Study Strategies Inventory (LASSI) at the beginning and the end of semester. Students in the intervention group studied different components of reading and learning skills using team working. Their final scores were calculated based on written reports on application of study skills in exams (portfolio), self-evaluation form and their progress in LASSI test. The mean differences of scores before and after intervention in each of ten test scales were compared between two groups. RESULTS: The results showed that the mean difference scores in attitude, time management, information processing, main ideas selection, study aids and self testing scales were significantly higher in the intervention group (p < 0.05 for all). CONCLUSIONS: This optional course successfully improved learning strategies in the corresponding classroom activities. However, there was no improvement in the motivational scale which is tightly related to the educational success. Therefore, the implementation of educational programs with an emphasis on meta cognitional aspects of learning is recommended. PMID- 22091255 TI - Takotsubo cardiomyopathy or broken heart syndrome: A review article. AB - Stress-induced cardiomyopathy or Takotsubo cardiomyopathy is a recently increasing diagnosed disease showed by transient apical or mid left ventricular dilation and dysfunction. This sign is similar to acute myocardial infarction but without significant coronary artery stenosis and intra coronary clots. On the other hand there are important and essential differences in their management. Consequently, our physicians should know about its pathophysiology, diagnosis and treatment. PMID- 22091257 TI - Thrombotic Thrombocytopenic Purpura associated with Clopidogrel: a case report and review of the literature. AB - Thrombotic Thrombocytopenic Purpura (TTP) is a life threatening, multisystem disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological changes, renal failure, and fever. These signs and symptoms are thought to be caused by microthrombi, composed of agglutinated platelets and fibrin, which deposit in the arterioles and capillaries without mediation by an inflammatory process. TTP can occur in the first two weeks of initiation of Clopidogrel therapy. Early signs of TTP may be a skin reaction, which may precede the onset of TTP or it may be other type of purpura or neurological changes. We report the clinical and laboratory findings in a 67 years old female patient in whom TTP developed soon after treatment with 40 mg/day oral Clopidogrel after 8 days. She developed thrombocytopenia (platelets count 12000 /mm3). Her clinical signs and symptoms were fever (39.6C), bleeding from the nose and gum, large skin bruises (purpura and ecchymoses), neurological changes including hallucinations, bizarre behavior, altered mental status (fluctuating), headache, and renal dysfunction. Physicians should be aware of the possibility early onset of this syndrome when initiate Clopidogrel treatment. PMID- 22091258 TI - Intracranial foreign body granuloma simulating brain tumor: a case report. AB - Intracranial foreign body granulomas are rarely reported. Clinical symptoms caused by foreign body granulomas can be noticed from months to many years after surgical procedure. The most common reported etiology is suture material. A 45 year-old woman was presented with grand mal epilepsy. She was operated for brain tumor 19 years ago. In CT scan, a round radio-dense mass resembling a tumor at anterior fossa was seen. She underwent craniotomy and resected a granuloma with cotton fibers surrounded by yellow capsule without residual or recurrent tumor. Granuloma can mimic intracranial meningioma and special attention should be paid not to leave cotton pledgets during operations. PMID- 22091259 TI - Effects of low dose methotrexate on relapsing-remitting multiple sclerosis in comparison to Interferon beta-1alpha: A randomized controlled trial. AB - BACKGROUND: Methotrexate, a toxic antimetabolite that limits cellular reproduction by acting as an antagonist to folic acid, has been used to control autoimmune disease with different results. The aim of this study was to evaluate the effectiveness of low dose Methotrexate in the relapsing-remitting multiple sclerosis (RRMS). METHODS: Eighty patients with definite RRMS aged 15 to 55 years were randomly allocated to receive a 12-month treatment course of either oral Methotrexate (7.5 mg/week) or intramuscular Interferon beta-1alpha (30 MUg/week). Response to treatment was assessed at 12 months after start of therapy. RESULTS: The results of the study demonstrated significant reduction in relapse rate in both groups (p < 0.01). In 40 patients treated by Methotrexate, the mean value (SD) of relapse rate decreased from 1.75 (0.74) to 0.97 (0.83) (p < 0.01). Correspondingly, the mean value (SD) of relapse rate in patients treated by Interferon beta-1alpha decreased from 1.52 (0.59) to 0.57 (0.78) (p < 0.01). Decrease of relapse rate in Interferon beta-1alpha group was more than that in the other group (p = 0.06). CONCLUSIONS: This study suggests that although treatment with Methotrexate may significantly reduce relapse rate and slow progression of disease in patients with RRMS, its efficacy is less than Interferon beta-1alpha and it may be better used as add-on therapy. PMID- 22091260 TI - Comparing the outcomes of open surgical procedure and percutaneously peritoneal dialysis catheter (PDC) insertion using laparoscopic needle: A two month follow up study. AB - BACKGROUND: This study was performed to compare the outcomes of open surgical procedure and percutaneously peritoneal dialysis catheter (PDC) insertion using laparoscopic needle. METHODS: This randomized clinical trial study was conducted in the Nephrology Department in Noor Hospital, Isfahan, Iran between 2009 and 2010. 64 uremic patients were randomized into two study groups using random allocation software. Thirty four catheters were inserted percutaneously (P group) and 30 catheters were placed surgically (S group). Collected information included demographic data, body mass index, and cause of renal disease, duration of operation and length of hospitalization. Outcomes were considered as mechanical and infectious complications. RESULTS: There were no significant differences in age, gender, the mean of body mass index, having history of hemodialysis, diabetes mellitus, hypertension, ischemic heart disease, and length of hospitalization. Hemopenitoneom was more frequent in S group than P group (13.3% versus 3.2%; p < 0.0001). There was no significant difference between two groups in early peritonitis, early leakage, hernia, hollow viscous perforation, catheter obstruction, and malpositioning and the time of peritoneal dialysis onset. Outflow failure and the exit site infection were more frequent in S group than P group (p < 0.0001). Mean of the operative time was longer in S group than P group (27.70 +/- 2.79 minutes versus 10.48 +/- 1.91 minutes, p < 0.001). CONCLUSIONS: Percutaneous catheter insertion has fewer rate of complications and is less time consuming in comparison with surgical method. PMID- 22091261 TI - Effects of daily milk supplementation on improving the physical and mental function as well as school performance among children: results from a school feeding program. AB - BACKGROUND: School feeding programs are important interventions for improving the nutritional status of students. Therefore, this study was conducted to evaluate the effects of milk supplementation on physical, mental and school performance of students. METHODS: This case-control population-based intervention was conducted on 469 students from 4 schools in a medium socio-economic status region in Tehran. The schools were chosen by Iranian ministry of education and training and they were allocated in case and control groups randomly. All the students in the first to third classes in the intervention schools were daily consumed sterilized and homogenized milk for three months (250 ml each). Anthropometric measurements were done according to the standard methods. For evaluating the mental function, the Raven's Coloured Progressive Matrices (CPM) and Wechsler Intelligence Scale for children (verbal, non-verbal, total Intelligent Quotient) were conducted on students. School performance was assessed by grade-point averages of each student. RESULTS: The weight of children was significantly different between control and intervention group at the end of the study among girls (23.0 +/- 3.8 vs. 23.8 +/- 4.3 kg; p < 0.05). Psychological tests' scores were significantly different between the control and the intervention groups (p < 0.05) at the end of the trial among boys. The grade-point average was significantly different at the end of the trial between the intervention and the control group among girls (p < 0.05). CONCLUSIONS: School feeding programs focus on milk supplementation had beneficial effects on the physical function and school performances specifically among girls in Iran. PMID- 22091262 TI - The efficacy of preventive parasternal single injection of bupivacaine on intubation time, blood gas parameters, narcotic requirement, and pain relief after open heart surgery: A randomized clinical trial study. AB - BACKGROUND: Postsurgical pain usually results in some complications in the patients. This study has tried to investigate the effects of parasternal single injection of bupivacaine on postoperative pulmonary and pain consequences in patients after open heart surgery. METHODS: In a prospective double blind clinical study, 100 consenting patients undergoing elective open heart surgery were randomized into two groups. In case group, bupivacaine was injected at both sides of sternum, immediately before sternal closure. In the control group, no intervention was performed. Then, the patients were investigated regarding intubation period, length of ICU stay, arterial blood gas (ABG) parameters, morphine requirement, and their severity of postoperative pain using a visual analogue scale (VAS) device. RESULTS: No differences were found between the two groups regarding to age, sex, pump time, operation time, and body mass index and preoperative cardiac ejection fraction. Mean intubation length in case group was much shorter than that in control group. Mean PaO(2) in case group was lower in different checking times in postoperative period. The patients in the case group needed less morphine compared to those in the control group during the 24-hour observation period in the ICU. Finally, mean VAS scores of pain in case group were significantly lower than those in control group at 6, 12, and 24 hours postoperatively. CONCLUSIONS: Patients' pain relief by parasternal single injection of bupivacaine in early postoperative period can facilitate earlier ventilator weaning and tracheal extubation after open heart surgery as well as achieving lower pain scores and narcotic requirements. PMID- 22091263 TI - Comparing angiography features of inferior versus anterior myocardial infarction regarding severity and extension in a cohort of Iranian patients. AB - BACKGROUND: The location of acute myocardial infarction (MI) is an important prognostic factor for risk stratification of patients with first ST-segment elevation MI (STEMI). The main goal of this study was to compare the severity and extension of coronary involvement in inferior and anterior MI. METHODS: This study reviewed angiographic reports of 579 patients with a first anterior wall STEMI and 690 with a first inferior STEMI that were referred to Tehran Heart Center between March 2004 and September 2007. The number of coronary vessels involvement and the presence of left main lesion were determined based on angiography reports. The Gensini score was also calculated for each patient from the coronary arteriogram. RESULTS: Incidence of left main lesion was similar between the two groups. Although coronary arteries involvement according to Gensini score was more severe in anterior wall MI group compared with inferior wall MI group, the number of involved coronary arteries was significantly higher in the inferior MI patients. Recommendation of coronary artery bypass grafting, percutaneous coronary intervention (PCI) or medical treatment were the same for both groups; however, patients with anterior MI were treated more with primary PCI. CONCLUSIONS: According to our angiography database, despite anterior wall MI is associated with more severity of coronary artery disease; inferior wall MI is more extent with regard to the number of involved coronary vessels. Location of MI can predict the severity and extension of infarction. PMID- 22091264 TI - The effect of omega-3 on the serum visfatin concentration in patients with type II diabetes. AB - BACKGROUND: Visfatin is an adipocytokine which is secreted from adipose tissue and can affect on the diabetes inflammatory reaction and also serum lipids level. On the other hand, Omega-3 can also prevent formation of insulin resistance. In the present study, the effect of Omega-3 on the serum visfatin concentration was evaluated. METHODS: 71 women with type II diabetes were randomly assigned to the group that took Omega-3 capsules or control group with placebo capsules. In the first step, study subjects filled a questionnaire collecting their age, height, weight, waist circumference, and hip circumference. Also their blood samples were taken for blood tests. In the second step, the intervention was done for 8 weeks and in the third step the aforementioned were collected again. In the blood samples visfatin and lipid profiles (low density lipoprotein [LDL], high density lipoprotein [HDL], triglyceride [TG], and cholesterol), glucose and HbA1c were measured. RESULTS: There was no significant difference in serum visfatin level between Omega-3 and placebo groups before the intervention (p = 0.14), while after the intervention, the mean serum visfatin level in the Omega-3 group was significantly higher (p < 0.001). In addition, the mean difference between the serum visfatin level before and after the intervention in both groups was significant (p < 0.001). CONCLUSIONS: This study showed an increase in visfatin level following consuming Omega-3 fats but according to controversial issues on insulin-like function of visfatin, the effects of Omega-3 on diabetes should be studied more in further studies. PMID- 22091265 TI - Seroepidemiology of Toxoplasma gondii infection in Isfahan province, central Iran: A population based study. AB - BACKGROUND: Toxoplasmosis is a worldwide infection. Most studies on toxoplasmosis are in women in child bearing ages. We conducted an epidemiological survey on the population of the Isfahan Province to identify characteristics of the individuals associated with seropositivity. METHODS: In a cross sectional study, 599 serum samples were randomly collected for seroepidemiology of Hepatitis A and E, and were also used for titration of IgG anti-toxoplasma gondii antibody by a commercial enzyme-linked immunosorbent assay (ELISA) kit. Data were analyzed using SPSS software(15). Chi square and Fisher exact tests were employed to examine antibody status in different age, gender, education and residency groups. RESULTS: The overall prevalence was 41.4% (248/599). There was a statistical significant association between seroprevalence with age, education, and gender (p < 0.05) but not with residency state. The peak age for acquisition of the infection in females was 20-29 and in males 20-39 years old. CONCLUSIONS: Results of current study showed a moderate prevalence of toxoplasma gondii infection. However higher seroconversion rate in active social and reproductive ages, females and low educated individuals necessitate active preventive programs in these high risk groups. PMID- 22091266 TI - Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery. AB - BACKGROUND: There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF). Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. METHODS: Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. RESULTS: The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05). Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57%) and 6 (52.17%) after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002), followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482 32.032 and p = 0.009) and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031). CONCLUSIONS: Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect. PMID- 22091267 TI - Effect of nasal beclomethasone spray in the treatment of otitis media with effusion. AB - BACKGROUND: Antimicrobials treatment of Otitis media (OM) reduces some complications, but some of chronic complications, and specially otitis media with effusion (OME), seem to increase. Theoretically the usage of nasal corticosteroid sprays may prevent this problem by reducing the local inflammation around the eustachian tube. So, this study aimed to evaluate the role of nasal corticosteroid spray as an adjuvant for the treatment of OME. METHODS: In a randomized, prospective clinical trial, 2 groups of 46 subjects who had OME were recruited. A questionnaire containing patients' characters, history, complaints, otologic examinations, and the report of tympanometries was filled for all before and after treatment. We administered a period of amoxicillin and a decongestant for both group and nasal beclomethasone spray only for case group. RESULTS: Thirty five of cases (76.1%) and 22 (47.8%) of controls had an improvement in their symptoms or the quality of hearing (p = 0.005). Partial remission was the most common finding in 52.2% of the patients in the case group but for control group there was no change (p = 0.024). The higher improvement in the tympanic retraction in the case group was significant (p < 0.05). A significant better tympanometric result has showed in the treatment of left ear in the patients of the case group (p = 0.038) but not for right ear (p = 0.136). CONCLUSIONS: We concluded that the administration of nasal beclomethasone spray as an adjuvant for the treatment of OME not only improved the results treatment but also increased the resolution of symptoms and the patients' quality of hearing. PMID- 22091268 TI - Efficacy of desmopressin in treatment of nocturia in elderly men. AB - BACKGROUND: Nocturia may be due to urological and non-urological diseases and some of the possible underlying non-urological diseases may be life-threatening. We investigated the efficacy and safety of lowest dose of oral desmopressin in treatment of nocturia in elderly men. METHODS: 60 old men referring to urology clinic of Imam Reza hospital in Tehran, Iran from 2008-2009 for treatment of nocturia were included in a double-blind placebo-controlled study. Patients were randomly divided into 2 study groups (30 patients in each group). Care was taken to match the patients of the 2 groups by age and clinical criteria. They complained of about 2 voids per night. We divided the patients into 2 study groups. Patients belonging to group A (n = 30) received placebo and patients of group B (n = 30) received 0.1 mg desmopressin at bed time for 8 weeks. Patients were assessed after 4 and 8 weeks of treatment. The means were compared using paired sample t-test and chi-square test for time of nocturia before and after treatments and also between the two groups. ANOVA test was used for assessement of statistical differences between outcomes of the two groups. RESULTS: Mean number of nocturia before and after receiving desmopressin were 2.6 and 1.6 respectively which differed significantly (p < 0.001). Mean number of nocturia before and after receiving placebo were 2.5 and 2.3 respectively with no significant difference (p = 0.344). After 4 weeks of treatment with desmopressin, 17 patients (56.7%) had less than 2 voids, 5 patients (16.7%) had 2 voids and 8 (26.7%) had more than 2 voids per night (p < 0.05). After 8 weeks, patients were evaluated and it was noticed that in group B, 4 patients (13.3%) had 2 voids, 24 (80%) had less than 2 voids and 2 patients (6.7%) had more than 2 voids per night (p = 0.004). CONCLUSIONS: Oral administration of desmopressin is an effective and well-tolerated treatment for nocturia in elderly men. PMID- 22091269 TI - Spinal anesthesia versus general anesthesia for elective lumbar spine surgery: A randomized clinical trial. AB - BACKGROUND: Either general or regional anesthesia can be used for lumbar disk surgery. The common anesthetic technique is general anesthesia (GA). The aim of this study was to compare the intra and postoperative outcomes of spinal anesthesia (SA) with GA in these patients. METHODS: Seventy-two patients were enrolled in the study. They were randomized into two groups with 37 patients in GA Group and 35 ones in SA Group. The heart rate (HR), mean arterial pressure (MAP), blood loss, surgeons satisfaction with the operating conditions, the severity of postoperative pain based on visual analogue scale (VAS) and analgesic use were recorded. RESULTS: The mean blood loss was significantly less in the SA Group compared to GA Group (p < 0.05). Intraoperative maximum blood pressure and heart rate changes were significantly less in SA Group (p < 0.05). The surgeons satisfaction was significantly more in the SA Group (p < 0.05). The number of patients who used postoperative analgesic as well as postoperative mean VAS was significantly less in SA Group in comparison with GA group (p < 0.05 for both). CONCLUSIONS: Our study showed that SA was superior to GA in providing postoperative analgesia and decreasing blood loss while maintained better perioperative hemodynamic stability without increasing adverse side effects. PMID- 22091270 TI - The relationship between parameters of static and dynamic stability tests. AB - BACKGROUND: Stability is often described to be static (quiet standing) and dynamic (maintaining a stable position while undertake a prescribed movement). Many researchers have used only static tests to evaluate the stability of normal and handicapped subjects. However, it is important to evaluate the stability of subjects while undertaking various tasks (dynamic stability). It is not currently clear whether static balance can predict dynamic balance or not. Therefore, the aim of this research was to investigate the relationship between parameters of static and dynamic stability tests. METHODS: The current clinical trial study was carried out in the Bioengineering Unit of Strathclyde University during 2008 and 2009. The normal subjects with no history of musculoskeletal disorders from staff and students of the Unit were selected in this study. Twenty-five normal subjects were recruited to participate in this research project. They were asked to stand on a force plate in quiet standing and while undertaking various hand tasks. The functional stability of the subjects was measured while transverse and vertical reaching tasks were undertaken. The correlation between various parameters of stability in quiet standing and functional hand tasks was evaluated using Pearson correlation. RESULTS: There was no significant correlation between static and dynamic stability parameters. The Pearson correlation coefficients for all parameters regarding the static and dynamic tests were less than 0.46. CONCLUSIONS: As there was no correlation between stability parameters in quiet standing and while performing various hand tasks, it is not practical to discuss ability of the subjects to control their balance while undertaking various hand tasks based on static balance ability. PMID- 22091271 TI - Comparing immune response of intradermal low dose versus intramuscular high dose of hepatitis B vaccination in hemodialysis patients. AB - BACKGROUND: Hepatitis B is the most important cause of cirrhosis in developing countries. Hemodialysis patients are susceptible to infection due to repeated contact with dialysis machines and blood products. The aim of this study was to compare the efficacy of intradermal low dose with intramuscular high dose hepatitis B vaccination in hemodialysis patients. METHODS: In a cross-sectional study on 24 hemodialysis patients that not responded to conventional method of vaccination in this center (double dose in 0, 1 and 6 months) and have antibody titer less than 10 mu/ml were enrolled to intramuscular or intradermal group, randomly. In intradermal (ID) group 10 MUg (0.5 ml) recombinant vaccine, every 2 weeks to 6 months and in intramuscular (IM) group 40 MUg (2 ml) at 0, 1, 2, and 6 months were prescribed and antibody titer were checked after 1 and 3 months of the end of vaccination. RESULTS: Mean HBS antibody titer in patients was 4.4 +/- 3.1 mu/ml at the beginning of study (minimum: 1.1 mu/ml and maximum: 9.2 mu/ml) and after 1 month and 3 months, mean HBS antibody were 190.4 +/- 59 and 223.3 +/- 83.9, respectively (p < 0.001). After one month, in intradermal and intramuscular groups, mean HBS antibody was 198.8 +/- 75.6 mu/ml and 181.2 +/- 61.8 mu/ml, respectively (p = 0.5) and after 3 months it was 230 +/- 76 mu/ml and 216.2 +/- 94.3 mu/ml, respectively (p = 0.83). CONCLUSIONS: Antibody titer was high (> 50 mu/ml) in two groups after 1 and 3 months of vaccination and no significant difference was found between the 2 groups. Therefore, two methods of vaccination (high dose IM and low dose SC) are equally effective and the selection of vaccination method is based on health policy. PMID- 22091272 TI - Designing a health equity audit model for Iran in 2010. AB - BACKGROUND: Health equity audit, as an alternative solution, is a process by which local partners systematically review inequalities in the patients' health, their access to appropriate services and health system outputs. Then, necessary activities needed in order to have more equitable services are agreed on and these concurrences become the executive scheme and action initiates. Therefore, it is pivotal for health care organizations to pay special attention to this important topic. The objective of the current study was to review the health equity audit model in different countries to gather viewpoints of various involved groups in health sector, particularly health experts, and to offer a practical and appropriate model for health equity audit in Iran. METHODS: This study adopted applied research approach in two phases. In the first step, this study conducted theoretical health equity audit models in the texts; the experiences of other countries were studied and the most appropriate model for Iranian health system was selected. In the second step, this study employed the Delphi technique. According to the Delphi technique the questionnaire applied in order to gather data and then, the final model was extracted. RESULTS: Agreeable topics, performing agencies, 6 equity audit stages, and equity indicators under 3 main parts with 16 sub-sections were elaborated and viewpoints of Iranian experts in the above fields were gathered and presented as the proposed health equity audit model for Iran. CONCLUSIONS: This study reviewed the model of health equity audit for UK and provided a comparative model for health system of Iran with respect to the opinions of academic experts. PMID- 22091273 TI - Childhood obesity and parks and playgrounds: A review of issues of equality, gender and social support. AB - The childhood obesity has been a growing concern over the last decade all over the world. Built environmental characteristics such as parks and playgrounds serves as a reference point for physical activity in children. The equality issues related to ethnicity, Social Economic Status (SES), gender and social support have been related with both physical activity and presence and quality of parks and playgrounds. However, only limited studies have addressed these issues in children. The current paper is a general enumerative review that would discusses the above issues with respect to obesity in all age groups, giving particular emphasis to childhood obesity. The importance of this review is to further explore the importance and highlight the findings related to these issues, so that future original studies could be planned keeping these associations in mind. PMID- 22091274 TI - Evidence-based history taking under "time constraint". AB - Physicians all through the world visit patients under time limitations. The most important troubled clinical skill under "time constraint" is the diagnostic approach. In this situation, clinicians need some diagnostic approaches to reduce both diagnostic time and errors. It seems that highly experienced physicians utilize some special tactics in this regard. Evidence-based medicine (EBM) as a relatively new paradigm for clinical practice stresses on using research evidences in diagnostic evaluations. The authors aimed to evaluate experts' strategies and assess what EBM can add to these tactics. They reviewed diagnostic strategies of some veteran internists in their busy outpatient clinics and proposed an evidence-based diagnostic model engaging clinical experience and research evidence. It appears that every clinician utilizes a set of "key pointer" questions for decision-making. In addition to use of evidence-based resources for making differential diagnosis and estimating utility of various diseases, clinicians should use "key pointers" with significant likelihood ratios and from independent systems to reduce time and errors of history taking. Clinical trainees can improve their practice by constructing their own set of pointers from valid research evidences. Using this diagnostic model, EBM can help physicians to struggle against their "time constraint". PMID- 22091275 TI - Huge retroperitoneal liposarcoma. AB - Liposarcoma are one of the common soft tissue sarcomas of adulthood which are remarkable because of their frequently large size. We report a case with an extremely large well-differentiated retroperitoneal liposarcoma that weighted 32 kilograms. The patient had relapse about one year later and two recurrent tumors were successfully excised. PMID- 22091276 TI - Metastatic medullary thyroid carcinoma: A case report. AB - Medullary thyroid carcinoma accounts for 4% of thyroid carcinoma and originates from parafollicular cells, secreting calcitonin and carcinoembryonic antigen (CEA). Conventional radiographic modalities such as Computerized Tomography (CT), Magnetic Resonance Imaging (MRI), and Ultrasonography (U/S), are used for detecting recurrences following total thyroidectomy. However, metastatic disease frequently escapes detection by the above modalities, even when its presence is suggested by persistently elevated serum calcitonin levels. In this paper, we report a case of medullary thyroid carcinoma in a 40 year-old woman who had whole body octreotide scintigraphy to evaluate and detect the origin of calcitonin and CEA secretion. PMID- 22091277 TI - Malignant endometrial polyps: Report of two cases and review of literature with emphasize on recent advances. AB - Endometrial polyps are common pathologic findings in gynecologic pathology practice. Although malignant changes in these lesions are uncommon, numerous studies confirmed this association especially with endometrial serous and clear cell carcinoma. Two cases of malignant endometrial polyps in association with presumed precursor lesion in one of them are presented. PMID- 22091278 TI - Theory based health education: Application of health belief model for Iranian patients with myocardial infarction. PMID- 22091279 TI - Fish oil increases atherosclerosis and hepatic steatosis, although decreases serum cholesterol in Wistar rat. AB - BACKGROUND: It is known that fish oil consumption decreases incidence of cardiovascular disease. However, some studies showed that it increases atherosclerosis as it does not get completely metabolized by the liver. The aim of the present study was to investigate the effects of fish oil on aortic atherosclerosis, hepatic steatosis and serum lipids in rats. METHODS: Twenty pregnant Wistar rats were fed with a fish oil-containing diet or standard diet (containing soy bean oil) during pregnancy and lactation and the pups were weaned onto the same diet. Fasting blood samples, hepatic and aortic specimens were taken from pups on day 70 postnatal. Data were analyzed with SPSS software, using t-test, Mann-Whitney test and Spearman correlation coefficient. Values of p < 0.05 were considered significant. RESULTS: Medians for fatty streak in aorta of fish oil fed and soy bean oil fed pups were 1.00 and 0.00, respectively, and P value was 0.042. Also, medians for ductular cell hyperplasia of liver in fish oil fed and soy bean oil fed pups were 1.00 and 0.00, respectively, and P value was 0.014. Total cholesterol in pups fed with fish oil was 52.20 mg/dl and in pups fed with soy bean oil was 83.90 mg/dl (p < 0.00) and for low density lipoprotein cholesterol (LDL-C) values were 8.79 mg/dl and 13.16 mg/dl, respectively (p = 0.031). CONCLUSIONS: According to the results of the present study, a diet which provided 15.9% of energy from fish oil as the only source of dietary fat, induced aortic atherosclerosis as well as hepatic steatosis in Wistar rat, although it decreased total cholesterol and LDL-C. PMID- 22091280 TI - Thoracic computerized tomographic (CT) findings in 2009 influenza A (H1N1) virus infection in Isfahan, Iran. AB - BACKGROUND: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT) scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1) in an appropriate clinical setting. METHODS: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23(rd) 2009 to February 20(th) 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1) virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. RESULTS: Patchy infiltration (34.6%), lobar consolidation (30.8%), and interstitial infiltration (26.9%) with airbronchogram (38.5%) were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8%) showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS). CONCLUSIONS: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1) in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific. PMID- 22091281 TI - The evaluation of Tetanus-diphtheria (Td) vaccine impacts on immune response to hepatitis B (HB) vaccine in non-responder dialysis patients. AB - BACKGROUND: The Hepatitis B (HB) vaccine response in hemodialysis patients is less than healthy individuals. Different strategies have been taken into account to improve the response rate. This study aimed to evaluate the effect of tetanus and diphtheria (Td) vaccine as an adjuvant therapy to HB vaccination. METHODS: Sixty three end-stage renal disease patients were recruited on dialysis that were older than 18 years and had passed at least 3 doses of HB vaccination schedule, and had HBS antibody (Ab) with titer less than 10 IU/L. The patients were divided into two groups; A (30 patients) and B (33 patients). Both of the groups received a 3-dose HB vaccination schedule of 40 MU g intramuscularly in the left deltoid muscle at 0, 1 and 6 months. Group A also received Td vaccine intramuscularly simultaneous with the first dose of HB vaccine. HBS Ab was measured in periods of 1 and 6 months after completion of the vaccination. RESULTS: One month after completion of the vaccination, group A had better but not significant response rate (96%) than group B (83.9%) (p > 0.05); in addition, after 6 month there was no difference between the two groups (87.5% vs. 83.3%) (p > 0.05). Patients with HCV infection had lower response rate than patients who did not have HCV infection (33.3% vs. 92.5%) (p < 0.05). Age had negative effect on immune response to HB vaccination (r = -0.339; p = 0.005). CONCLUSIONS: The use of Td vaccine concurrent with HB vaccination may increase the response rate in non responder individuals; however, it seems it does not have any role in the persistence of immune response. Age and HCV infection negatively affected the response to HB vaccination in dialysis patients. PMID- 22091282 TI - The effects of bare metal versus drug-eluting stent implantation on circulating endothelial cells following percutaneous coronary intervention. AB - BACKGROUND: The purpose of this study was to compare the effects of bare metal stents (BMS) and drug-eluting stents (DES) implantation on circulating endothelial cells (CECs) which have been proposed as cellular markers of endothelial dysfunction following percutaneous coronary intervention (PCI). Recently, it has been established that DES further reduce restenosis and revascularization rate compared to bare metal stents in elective procedures. However, its benefits are compromised by the stent-related thrombosis events. METHODS: 22 patients who were candidate of PCI were included in this study. The patients underwent DES implantation (n = 11) or BMS implantation (n = 11). In all patients the numbers of CECs were determined before and a week after stent implantation using flow cytometry and the obtained data were compared within and between groups by paired and unpaired Student's t-test, respectively. CECs were defined as cells negative for CD45 (FITC) and highly double positive for CD146 (PE) and CD34 (PE-Cy5) expression. RESULTS: There were no significant differences in the baseline levels of CECs between two groups (p = 0.96). Stent implantation led to a significant increase in CECs compared with the preprocedural levels in the BMS group (p = 0.005) whereas there was a significant decrease in CEC numbers in DES group (p < 0.001). One week after stent implantation CECs count in BMS group was significantly higher compared to DES group (p < 0.001). CONCLUSIONS: The results indicate that patients undergoing DES implantation were subjected to less endothelial injury than patients receiving BMS as indicated by CEC enumeration. PMID- 22091283 TI - Target-controlled infusion of remifentanil with propofol or desflurane under bispectral index guidance: quality of anesthesia and recovery profile. AB - BACKGROUND: Our objective was to examine the clinical properties of two anesthetic regimens, propofol target-controlled infusion (TCI), or desflurane using remifentanil TCI under bispectral index (BIS) guidance during ear, nose, and throat (ENT) procedures. METHODS: FORTY CONSENTING PATIENTS WHO SCHEDULED FOR ENT PROCEDURES WERE PROSPECTIVELY STUDIED AND WERE INCLUDED IN ONE OF THE TWO GROUPS: TCI group or desflurane (DES) group. General anesthesia was induced with 3 ng mL(-1) and 4 MUg mL(-1) effect site concentrations (Ce) of remifentanil and propofol, respectively, with TCI system. After intubation, while propofol infusion was continued in the TCI group, it was ceased in the DES group and desflurane with an initial delivered fraction of 6% was administered. The Ce of propofol infusion and inspired fraction of desflurane was adjusted in order to keep BIS as 50 +/- 10. RESULTS: General mean values of mean arterial pressure (MAP) and heart rate (HR) for the TCI group was significantly higher than DES group (89.3 mmHg and 72.4 bpm vs. 77.1 mmHg and 69.5 bpm). Early emergence from anesthesia did not significantly differ between the groups. The rate of patients' Aldrete score (ARS) to reach 10 was found to be 100% at the 15(th) min in both groups. CONCLUSIONS: Bispectral index guided combinations of remifentanil TCI either with propofol TCI or desflurane anesthetic regimens are both suitable for patients undergoing ENT surgery. The lower blood pressure in the remifentanil TCI with desflurane anesthetic regimens may be a significant advantage. PMID- 22091284 TI - The effect of impregnated autogenous epidural adipose tissue with bupivacaine, methylprednisolone acetate or normal saline on postoperative radicular and low back pain in lumbar disc surgery under spinal anesthesia; A randomized clinical trial study. AB - BACKGROUND: Low Back Pain (LBP) and radicular leg pain (RLP) after lumbar disc surgery are great challenges that prevent patients and neurosurgeons in making a surgical decision. By spinal anesthesia, LBP and RLP diminish up to 2 to 3 hours postoperatively. The aim of this study was to determine the effect of impregnated epidural adipose tissue (EAT) with bupivacaine or methylprednisolone acetate on reduction of late postoperative pain after spinal anesthesia. METHODS: This study was performed on lumbar disc herniation surgery under spinal anesthesia. Sixty six patients entered our study who were divided into three groups, EAT impregnated with bupivacaine (group 1), methylprednisolone acetate (group2) and normal saline (control group). The LBP and RLP were evaluated during the first 24 hours postoperatively and 14 days later by visual analogue scale (VAS). RESULTS: Of 66 patients, 53% were female and 47% male. The average (SE) LBP in the first 6 hours after surgery based on VAS were 1.59 +/- 0.90 in group one, 2.36 +/- 2.38 in group 2 and 3.09 +/- 1.41 in control group but the VAS for RLP in this period were 1.95 +/- 1.13, 1.31 +/- 1.39 and 2.40 +/- 1.09, respectively. The average LBP and RLP did not show any differences after 14 days postoperatively. CONCLUSIONS: According to our data bupivacaine was effective on LBP relief and steroid was effective on RLP relief during the first 12 hours after surgery. PMID- 22091285 TI - The relationship between type D personality and perceived social support in myocardial infarction patients. AB - BACKGROUND: Type D personality is based on two global and stable personality traits, including negative affectivity (NA) and social inhibition (SI). The aim of this study was to examine the relationship between type D personality and perceived social support in post myocardial infarction (MI) patients. METHODS: One hundred seventy six consecutive patients following MI admitted to the cardiac care unit (CCU) of nine hospitals in Isfahan, Iran from April to September 2006 were selected based on the inclusive and exclusive criteria. The patients completed the Persian version of type D personality scale and the Persian version of multidimensional scale of perceived social support (MSPSS). Also, demographic and medical questionnaire was completed for each patient. Chi-squared test, t test and MANOVA were used to analyze the data. RESULTS: The findings indicated that 35.8% patients (35.8 %) were classified as type D. The results of MANOVA showed that type D patients were significantly different from non-type D patients (F = 8.72, p = 0.0001) on MSPSS scores and on all dimensions including family subscale (F = 11.52, p = 0.001), friends subscale (F= 16.16, p = 0.0001) and significant others subscale (F = 5.04, p = 0.026). CONCLUSIONS: Type D personality substantially affects the way MI patients perceive availability of social support from different sources including family, friends, and significant others. One implication of this finding may be to develop tailor-made interventions for MI patients with type D. PMID- 22091286 TI - Correlation of spot urine protein-creatinine ratio with 24-hour urinary protein in type 2 diabetes mellitus patients: A cross sectional study. AB - BACKGROUND: Diabetic nephropathy is the major cause for chronic renal failure (CRF) and proteinuria is an independent risk factor for end stage renal disease. Hence, early identification and quantification of proteinuria is of prime importance in the diagnosis and management. METHODS: This study was conducted amongst 42 diabetic subjects from HSK hospital, Bagalkot. Twenty four-hour urine protein and random urine protein to creatinine ratio (P:C) was determined. Pearson's correlation, sensitivity, specificity, positive and negative predictive values were determined using 24-hour urinary protein as a gold standard for spot urine P:C ratio. ROC curve and area under curve was also determined using SPSS (11.5) software. All the results were expressed in mean+/-SD. RESULTS: Forty two diabetes mellitus patients participated in this study. The average of 24 hour urinary protein was 1.6 +/- 1.7 gm/day. The spot urine P:C ratio was 1.27 +/- 1.55. There was a positive correlation between 24 hours urinary protein and spot urine P:C ratio (r = 0.925, p < 0.0001). The area under the ROC curve for urine P:C ratio at various cutoff was 0.947 (95% confidence interval: 0.831-0.992, p < 0.0001). The sensitivity and specificity was 80.65% and 100% respectively at P:C ratio cutoff of 0.3. CONCLUSIONS: The random urine P:C ratio predicts the amount of 24-hour urinary protein excretion with high accuracy. Hence it can be used as a faster diagnostic substitute for 24-hour urinary protein estimation. PMID- 22091287 TI - The impact of generic form of Clopidogrel on cardiovascular events in patients with coronary artery stent: results of the OPCES study. AB - BACKGROUND: To compare the early and late cardiovascular events as well as side effects of Osvix, a generic form of Clopidogrel versus Plavix regimens in patients with chronic stable angina, undergoing bare metal stent (BMS) or drug eluting stent (DES) placement, this study was carried out. METHODS: A total of 442 patients with chronic stable angina who were scheduled for elective percutaneous coronary intervention (PCI) were included in a randomized, double blind, multi-centric clinical trial being performed in 6 distinct university hospitals in 5 cities of Iran from March 2007 to November 2009. Baseline, demographic and history of risk factors were recorded using the patients' medical charts. Stenting procedure was performed via transfemoral approach using low osmolar contrast agents. Patients underwent BMS or DES placements based on the physician selection and were randomly assigned to Osvix or Plavix groups. Patients were followed by telephone in 0 and 6 months intervals regarding the major adverse cardiovascular events (MACE) including death, myocardial infarction, in-stent thrombosis, stroke, target lesion revascularization, and target vascular revascularization. Angina episodes, bleeding, liver enzymes, neutrophils and platelets count were also assessed in these intervals. RESULTS: There was not any significant difference between these two groups regarding the baseline characteristics. In the DES group, the 6-month mortality rate and the incidence of MACE in Osvix and Plavix groups were 0.9% and 1.9% (p = 0.61) and 1.8% and 4.9% (p = 0.26), respectively. During the follow up period after DES or BMS placement, there wasn't any significant difference regarding neutrophil and platelet counts or liver enzymes between study groups. CONCLUSIONS: Using Osvix and Plavix are followed by similar major cardiovascular events and side-effect profile in patients undergoing PCI. PMID- 22091288 TI - Postoperative residual block in postanesthesia care unit more than two hours after the administration of a single intubating dose of atracurium. AB - BACKGROUND: Residual neuromuscular blockade continues to be a clinical problem after surgical procedures. The purpose of this study was to determine the incidence of residual paralysis in the postanesthesia care unit (PACU) after a single intubating dose of twice of the 95% estimated dose (ED95) of a nondepolarizing muscle relaxant with an intermediate duration of action. METHODS: Two hundred and sixteen patients scheduled for elective surgery under general anaesthesia requiring tracheal intubation were included in the study. They received a single intubating dose of intravenous atracurium (0.5 mg/kg) to facilitate tracheal intubation. At the end of surgery, if train of four (TOF) ratio was <= 0.9, neostigmine 40 MUg/kg intravenously was given. If TOF-ratio was >= 0.9, no neostigmine was given. Also, in awake patients with TOF > 0.9, residual neuromuscular paralysis was evaluated by using clinical tests such as head lift test and tongue depressor test. RESULTS: TOF was less than 0.9 in 48 (22.2%) patients while after 120 minutes, no patients had TOF less than 0.9. Of 33 patients whose operation lasted less than 120 minutes, 4 patients had TOF less than 0.9 at the end of surgery. There was no case of hypoventilation or hypoxia at PACU. The incidence of negative value in clinical tests was high. CONCLUSIONS: Our study gave the impression that more than two hours between the administration of a single intubating dose of an intermediate-acting nondepolarizing muscle relaxant (atracurium) and arrival to the PACU can probably guarantee the lack of a residual paralysis. PMID- 22091289 TI - Belonging to a peer support group enhance the quality of life and adherence rate in patients affected by breast cancer: A non-randomized controlled clinical trial. AB - BACKGROUND: Breast cancer is the most common cancer in women. It seems that breast cancer patients benefit from meeting someone who had a similar experience. This study evaluated the effect of two kinds of interventions (peer support and educational program) on quality of life in breast cancer patients. METHODS: This study was a controlled clinical trial on women with non-metastatic breast cancer. The patients studied in two experimental and control groups. Experimental group took part in peer support program and control group passed a routine educational program during 3 months. The authors administered SF-36 for evaluating the quality of life pre-and post intervention. Also, patient's adherence was assessed by means of a simple checklist. RESULTS: Two groups were similar with respect of age, age of onset of the disease, duration of having breast cancer, marital status, type of the treatment receiving now, and type of the received surgery. In the control group, there were statistically significant improvements in body pain, role-physical, role-emotional and social functioning. In experimental group, role-physical, vitality, social functioning, role-emotional and mental health showed significant improvement. Vitality score and mental health score in experimental group was significantly higher than that of the control group, both with p < 0.001. Also, it was shown that adherence was in high levels in both groups and no significant difference was seen after the study was done. CONCLUSIONS: According to the results of this study, supporting the patients with breast cancer by forming peer groups or by means of educational sessions could improve their life qualities. PMID- 22091290 TI - Depression and perceived social support from family in Turkish patients with chronic renal failure treated by hemodialysis. AB - BACKGROUND: Dialysis patients experience psychosocial problems, such as anxiety, depression, social isolation, loneliness, helplessness, and hopelessness. All of these psychosocial problems can increase patients' need for holistic care, including attention to the person's environment and receiving support from family. If dialysis patients are better supported and cared for, these negative consequences might be prevented or at least decreased. This study was performed to determine the perceived social support from family and depression level of hemodialysis patients. METHODS: In this study, descriptive design was used. Data were collected during structured interviews in an outpatient clinic using a questionnaire. The questionnaire aimed to determine the patients' descriptive characters and the scores of Beck Depression Inventory and Perceived Social Support from Family Scales. In data evaluation, descriptive statistics, Student's t tests, Kruskal Wallis tests, Mann-Whitney U tests and Pearson product moment correlations were used. RESULTS: The mean depression score was very high (23.2 +/ 10.5). Significant differences were found between employment status and level of depressive symptoms. The mean level of perceived social support from family was 15.23 +/- 5.37. There were no statistically significant differences between all the variables for the level of perceived social support from family. Perceived social support from family was negatively correlated with depression. CONCLUSIONS: The results of this study indicate that Turkish hemodialysis patients experience depression. However, patients who were dissatisfied with their social relationships had higher depression scores. PMID- 22091291 TI - Elevated plasma platelet-activating factor acetylhydrolase activity and its relationship to the presence of coronary artery disease. AB - BACKGROUND: Platelet-activating factor acetylhydrolase (PAF-AH) is a circulating enzyme that has an important role in the development of coronary artery disease (CAD). The correlations between PAF-AH and CAD are controversial. Furthermore, the differences of the enzyme levels between patients with stable and unstable CAD are not fully determined. The purpose of this study was to evaluate plasma PAF-AH levels and its association with the presence of CAD and some clinical risk factors in the patients. METHODS: This case-control study included 50 control subjects without CAD, 50 stable CAD patients and 50 unstable CAD patients with angiographically documented CAD. Plasma PAF-AH activity was determined by a commercial kit. The inflammatory markers, high sensitivity C-reactive protein (hsCRP) and oxidized low density lipoprotein (ox-LDL), and lipid profile were also measured. Comparisons of biochemical risk factors among all groups were performed by one way ANOVA. The association of PAF-AH activity with the presence of CAD was analyzed by multiple logistic regression. RESULTS: Plasma PAF-AH activity levels were higher in unstable CAD patients (0.040 +/- 0.012 MUmol/min/ml) than in stable CAD patients (0.032 +/- 0.010 MUmol/min/ml) and control subjects (0.026 +/- 0.009 MUmol/min/ml) (p < 0.01). Plasma PAF-AH activity was also independently associated with the presence of CAD (p< 0.01). CONCLUSIONS: Plasma PAF-AH activity levels were highly increased in unstable and stable CAD patients as compared to control subjects and may be a useful biomarker for CAD prediction. PMID- 22091292 TI - Asymptomatic falciparum malaria and intestinal helminths co-infection among school children in Osogbo, Nigeria. AB - BACKGROUND: Malaria and intestinal helminths are parasitic diseases causing high morbidity and mortality in most tropical parts of the world, where climatic conditions and sanitation practices favor their prevalence. The aim of this study was to determine the prevalence and possible impact of falciparum malaria and intestinal helminths co-infection among school children in Kajola, Osun state, Nigeria. METHODS: Fresh stool and blood samples were collected from 117 primary school children age range 4-15 years. The stool samples were processed using both Kato-Katz and formol-ether concentration techniques and microscopically examined for intestinal parasitic infections. Blood was collected by finger prick to determine malaria parasitemia using thick film method; and packed cell volume (PCV) was determined by hematocrit. Univariate analysis and chi-square statistical tests were used to analyze the data. RESULTS: The prevalence of Plasmodium falciparum, intestinal helminth infections, and co-infection of malaria and helminth in the study were 25.6%, 40.2% and 4.3%, respectively. Five species of intestinal helminths were recovered from the stool samples and these were Ascaris lumbricoides (34.2%), hookworm (5.1%), Trichuris trichiura (2.6%), Diphyllobothrium latum (0.9%) and Trichostrongylus species (0.9%). For the co infection of both malaria and intestinal helminths, females (5.9%) were more infected than males (2.0%) but the difference was not statistically significant (p = 0.3978). Children who were infected with helminths were equally likely to be infected with malaria as children without intestinal helminths [Risk Ratio (RR) = 0.7295]. Children with A. lumbricoides (RR = 1.359) were also likely to be infected with P. falciparum as compared with uninfected children. CONCLUSIONS: Asymptomatic falciparum malaria and intestinal helminth infections do co-exist without clinical symp-toms in school children in Nigeria. PMID- 22091293 TI - Evaluating the effectiveness of local dexamethasone injection in pregnant women with carpal tunnel syndrome. AB - BACKGROUND: Most of the medical treatments for carpal tunnel syndrome (CTS) have focused on suppressing the inflammatory process. An injection of dexamethasone acetate might provide the necessary cellular and humoral mediators to induce a healing cascade. Dexamethasone is a water-soluble steroid which is safe to be used in the third trimester, especially as a local treatment. The aim of this study was to evaluate the effectiveness of 4 mg dexamethasone acetate injection to treat carpal tunnel syndrome in pregnancy period. METHODS: Twenty pregnant women with CTS were recruited using strict inclusion and exclusion criteria. All the patients had been injected with 4 mg of dexamethasone acetate and 0.5 ml lidocaine 1% under the carpal tunnel. Pain intensity (based on visual analog scale or VAS) and electro physiologic parameters of median nerve (transcarpal median sensory nerve conduction velocity (SNCV), distal motor latency (DML) and distal sensory latency (DSL) were recorded before and 3 weeks after the injection. RESULTS: The average pain scores before and 3 weeks after the dexamethasone acetate injection was 8.70 +/- 0.92 and 4.30 +/- 0.76 respectively (p < 0.005). In addition, transcarpal SNCV of median nerve was 33.7 +/- 6.3 m/s and 24.5 +/- 6.8 m/s (p = 0.001); DML of median nerve was 5.16 +/- 1.04 ms and 4.70 +/- 0.53 ms (p = 0.001) and DSL of median nerve was 4.84 +/- 0.77 ms and 4.2 +/- 0.6 ms (p = 0.001), respectively. CONCLUSIONS: After dexamethasone acetate injection, pain intensity and electrophysiological parameters were significantly improved. This study offered encouraging results for an alternative minimally invasive treatment for CTS in pregnant women. PMID- 22091294 TI - Health research priority setting in Iran: Introduction to a bottom up approach. AB - BACKGROUND: Priority setting is one of the major issues in the health research system and no health system can afford to pay for every research they want to do, particularly in developing countries, so we decided to set the national main areas of the health research priorities. METHODS: In this study, according to Essential National Health Research (ENHR) strategy and with cooperation of all the Iranian universities of medical sciences and other stakeholders, the national health research priorities were extracted. RESULTS: The number of research priorities collected from the universities of medical sciences was 6723. Seventeen percent of the research priorities were related to basic science, 78 percent applied science, and 5 percent were related to developmental type. According to epidemiological classification, 50% of the research priorities were in descriptive form. In this process, 9 main extracted areas consist of communicable diseases, non-communicable disease, Health System Research, pharmaceutical sciences and Industry, basic science, traditional medicine and herbal medicine, nutrition, environmental health, and dentistry. And then for each area, five main projects were defined. CONCLUSIONS: In the Health Research System, the participatory priority setting is the main function based on needs assessment. PMID- 22091295 TI - Spontaneous isolated celiac artery dissection. AB - Dyspepsia with mild, stabbing epigastric discomfort without history of trauma is a very common symptom that emergency physicians see in their daily practice. Vascular emergencies, mostly the aortic dissection and aneurysm, are always described in the differential diagnosis with persistent symptoms. Isolated celiac artery dissection occurring spontaneously is a very rare diagnosis. The involvement of branch vessels is generally observed and patients show various clinical signs and symptoms according to the involved branch vessel. Here we are presenting a case with spontaneous isolated celiac artery dissection, without any branch vessel involvement or visceral damage, detected by computed tomography scans taken on admission. PMID- 22091296 TI - Pamidronate infusion improved two cases of intractable seronegative rheumatoid arthritise. AB - Pamidronate is a bisphosphonate derivative that can inhibit bone resorption by actions on osteoclasts and increase bone density in spite of treatment with steroids. This drug has the anti-inflammatory effect by increase apoptosis of monocytes. 5-10 percent of rheumatoid arthritis patients is seronegative and may be resistant to conventional disease modifying anti rheumatic drugs (DMARDs). Intravenous (IV) pamidronate can be effective in disease control in seronegative rheumatoid arthritis. We report two cases of seronegative and drug resistant rheumatoid arthritis that favorably responds to pamidronate. PMID- 22091297 TI - Choriocarcinoma of the breast; a case report and review of literatures. AB - Choriocarcinoma is an extremely rare pathology among breast malignancies. It is introduced by two distinct terms in the literatures: breast cancer with choriocarcinomatous features and metastatic choriocarcinoma to the breast. In this case report, the history, physical examination, laboratory findings, imaging studies, and pathological findings of breast choriocarcinoma in a 41-year-old woman are described and previous literatures about choriocarcinoma in the breast are reviewed. PMID- 22091298 TI - Comment on Attari et al: Spinal anesthesia versus general anesthesia for elective lumbar spine surgery: randomized clinical trial. PMID- 22091299 TI - Hypoadiponectinemia in obese subjects with type II diabetes: A close association with central obesity indices. AB - BACKGROUND: Adiponectin is an adipocyte secreted protein with important biological functions Hypoadiponectinemia is associated with obesity, insulin resistance, and type II diabetes This study aimed to evaluate serum adiponectin level in obese subjects with type II diabetes and its correlation with metabolic parameters METHODS: This cross-sectional study was performed on 40 obese subjects with type II diabetes and 40 non-diabetic obese control subjects Fasting lipid profile was measured by the enzymatic methods The NycoCard HbA1c protocol was used to measure HbAlc The Serum adiponectin, insulin and glucose levels were measured using an enzyme immunoassay and glucose oxidase methods respectively RESULTS: Type II diabetes was associated with hypoadiponectinemia, in both men and women Serum adiponectin level in non-diabetic subjects (6.44 +/- 2.47 MUg/ml) was significantly higher than diabetics (4.55 +/- 1.88 MUg/ml) Furthermore, serum adiponectin concentration in females was significantly higher than males in non diabetics (7.18 +/- 2.68 vs 5.61 +/- 0.57) and diabetic groups (5.18 +/- 2.08 vs 3.99 +/- 1.5) There was a negative and significant correlation between serum adiponectin level with waist (r = -0.451, p = 0.003), waist to hip ratio (r = 0.404, p = 0.01) and BMI (r = - 0.322, p = 0.042) and a positive correlation with HDL (r = 0.337, p = 0.034) in non-diabetic group In diabetic group, there was only found a negative correlation between adiponectin and waist size (r = -0.317, p = 0.046) CONCLUSIONS: Obesity and type II diabetes are associated with low serum adiponectin concentration. PMID- 22091300 TI - Impact of health belief modification on intention to make smoke free home among pregnant women. AB - BACKGROUND: This study examined the effects of health education on modification of health belief and intention among pregnant women to have smoke free home. METHODS: In this randomized controlled study, 91 pregnant women completed the study in two groups. Intervention group was educated about the harms of environmental tobacco smoke (ETS) exposure. The Health Belief Model (HBM) was a framework for analyzing the beliefs. After 10-12 weeks, the HBM constructs and weekly ETS exposure at home were compared between the two groups. RESULTS: After performing educational program, the subjects in intervention group perceived more susceptibility and severity and reported lower weekly ETS exposure at home than subjects in control group; but, the self efficacy and perceived barrier were not different. The relationships between HBM constructs and weekly ETS exposure were significant; but, there was no significant difference in point prevalence of having smoke free home. CONCLUSIONS: This study indicated that the health education about ETS exposure can modify health belief and reduce EST exposure among pregnant women, but cannot affect the self efficacy and perceived barrier. To have smoke free home, they need to increase their self efficacy. PMID- 22091301 TI - Genetic variation in the association of air pollutants with a biomarker of vascular injury in children and adolescents in Isfahan, Iran. AB - BACKGROUND: Some experimental studies revealed that exposure to air pollution increases the expression of tissue factor (TF) in atherosclerotic lesions. We aimed to investigate the role of TF +5466A>G (rs3917643) polymorphism in the association of air pollution on serum levels of TF as a biomarker of vascular injury in children. METHODS: This cross-sectional study was conducted among 110 children, consisting of 58 (52.8%) girls and 52 (47.2%) boys with a mean age of 12.7 +/- 2.3 years, living in Isfahan, Iran. Enzyme-linked immunosorbent assay were used for measurement of serum TF. Genotype of +5466A>G (rs3917643) polymorphism was determined by the polymerase chain reaction-restriction length fragment polymorphism (PCR-RFLP) method. RESULTS: We identified 2 individuals with +5466AG genotype and 108 homozygous for the +5466A allele (no +5466GG homozygotes). The mean pollution standards index (PSI) value was at moderate level, the mean particular matter measuring up to 10 MUm (PM(10)) was more than twice the normal level. Multiple linear regression analysis showed that after adjustment for confounding factors (weight status, dietary and physical activity pattern), serum TF level had significant relationship with PSI (beta: 0.55, SE: 0.07, p<0.000) and PM(10) (beta: 0.51, SE: 0.03, p=0.001). CONCLUSIONS: In spite of similar genetic polymorphism of TF, air pollutants might have an independent association with systemic inflammatory and coagulation responses. The harmful effects of air pollutants on the first stages of atherosclerosis in the pediatric age group should be underscored in primordial and primary prevention of chronic diseases. PMID- 22091302 TI - The effectiveness of cognitive behavioral stress management training on mental health, social interaction and family function in adolescents of families with one Human Immunodeficiency Virus (HIV) positive member. AB - BACKGROUND: This study evaluated stress management training to improve mental health, social interaction and family function among adolescents of families with one Human Immunodeficiency Virus (HIV) positive member. METHODS: There were 34 adolescents (13-18 years old) with at least one family member living with HIV from whom finally 15 attended the study and participated in 8 weekly sessions of stress management training. The tests used in this study were: Strengths and Difficulties Questionnaire (self and parent report), General Health Questionnare 28 (GHQ-28) and Family Assessment Device (FAD), conducted before, after and three months after the intervention. The collected data were analyzed by repeated measure test using SPSS software (Version 18.0). RESULTS: Adolescents with one HIV positive family member showed high level of emotional problem (40%) and conduct problem (33.3%). There was a significant difference between before, after and 3months after intervention based on GHQ-28 mean scores and FAD mean sores (p < 0.001). There was a significant difference between mean scores of peers' relationship based on SDQ (self report and parents report forms) before and after intervention, but there was no significant difference between mean scores of pro social behavior based on SDQ (self report and parents report forms) in all three stages (before, after and three months after intervention). CONCLUSIONS: Stress management training is effective in improving mental health, family function and social interaction among adolescents living with parents infected with HIV/AIDS. PMID- 22091303 TI - Diagnostic performance of electrocardiography in the assessment of significant coronary artery disease and its anatomical size in comparison with coronary angiography. AB - BACKGROUND: Current study addressed the predictive value of 12-lead electrocardiogram (ECG) in patients with suspected coronary artery disease (CAD). METHODS: Four hundred consecutive patients with new onset of chest pain were studied. A resting standard 12-lead ECG was recorded and all patients underwent coronary angiography. RESULTS: ECG correctly detected significant stenosis in 176 out of 400 patients with an overall sensitivity per patient of 51.5% and specificity per patient of 66.1%. Based on artery analysis, ECG had the highest and lowest sensitivity for the detection of involvement in LAD (37.3%) and RCA (25.8%), respectively. ROC curve analysis showed that ECG changes were not good indicators of coronary arteries involvement with areas under the ROC curves 0.586 (for LAD artery), 0.524 (for RCA artery) and 0.530 (for LCX artery). CONCLUSIONS: ECG has low partial sensitivity and specificity for predicting coronary artery stenosis with accuracy ranged 58.5 to 62.0 percent based on coronary artery analysis. PMID- 22091304 TI - Clients' satisfaction with primary health care in Tehran: A cross-sectional study on Iranian Health Centers. AB - BACKGROUND: Primary health care system is the basic core of public service provision in Iran. This study aimed to assess clients' satisfaction with primary health care in Tehran, the capital of Iran, as a metropolitan. METHODS: Through a cross-sectional study in 2009-10, four urban primary health care clinics were selected through stratified random sampling. Four hundred participants were interviewed in the selected clinics about their satisfaction with the primary health care services and setting. Six domains of satisfaction including accessibility to services, continuity of care, humaneness of staff, comprehensiveness of care, provision of health education and effectiveness of services were calculated from selected variables. The descriptive statistics, chi square and t-tests were used when appropriate. RESULTS: The mean age of users of health services was 31.3 years (SD=9.6). Thirteen percent of participants were male. The most common reasons for asking health services reported as vaccination, family planning and children care. Overall, primary health care services were suitable for eighty percent of the participants. The mean and standard deviation for Access to services was 2.11 (SD=3.44), continuity of care was -0.35 (SD=3.49), humanness of staff was 3.93 (SD=5.70), comprehensiveness of care was 0.53 (SD=3.66), provision of health educational materials was -1.45 (SD=3.64) and effectiveness of services was 4.30 (SD=7.47). CONCLUSIONS: Primary health care is a comprehensive and suitable strategy to provide health services in public health. Package of services in primary health care may affect clients' satisfaction. Using family doctors may improve the indices. PMID- 22091305 TI - The prevalence of metabolic syndrome and insulin resistance according to the phenotypic subgroups of polycystic ovary syndrome in a representative sample of Iranian females. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with metabolic abnormalities which are also parts of metabolic syndrome (MetS). It is debated whether all women with PCOS should be screened for MetS and Insulin resistance (IR), since they may vary in terms of PCOS phenotype, ethnicity and age. This large scale study aimed to determine the prevalence of MetS among Iranian women diagnosed with different phenotypic subgroups of PCOS based on the Rotterdam criteria. METHODS: This study was conducted from January 2006 to June 2008 in Isfahan, Iran. The study population comprised females diagnosed with PCOS referred to the infertility clinic. The subjects were divided into for subgroups according to different phenotypes of PCOS based on the Rotterdam criteria. They underwent metabolic screening according to NCEP ATP III guidelines and IR screening based on homeostasis model assessment (HOMA) of insulin resistance. RESULTS: The prevalence of MetS and IR were 24.9% and 24.3%, respectively. A significant difference in the prevalence of MetS was documented between anovulatory women having PCOS with or without hyperandrogenism (23.1% and 13.9%, respectively; P = 0.001). Likewise, in PCOS women with hyperandrogenism, the MetS prevalence differed among those with or without polycystic ovary (23.1% and 63.8%, respectively; P = 0.001). CONCLUSIONS: The prevalence of MetS and IR varies between the phenotypic subgroups of PCOS. Hyperandrogenemia PCOS phenotypes of Iranian women, in particular those without sonographic polycystic ovary, are highly at risk of MetS and IR. PMID- 22091306 TI - Comparative evaluation of different values of bispectral index in determination of the appropriate level of anesthesia for tracheal intubation during inhalational induction of anesthesia in pediatrics. AB - BACKGROUND: Induction of anesthesia is the most crucial period of general anesthesia. Inhalational induction is the most commonly used technique in pediatric anesthesia. Tracheal intubation can be done after reaching the deep levels of anesthesia. The depth of anesthesia is often difficult to be judged. Bispectral index is a measure of the effects of anesthesia on brain. This study was designed to evaluate the efficacy of bispectral index (BIS) in clarifying suitable depth of anesthesia for tracheal intubation during inhalational induction of anesthesia. METHODS: In a clinical trial, ninety patients, ASA I & II, 1 to 6 years old, scheduled for elective surgery were enrolled into the study. After starting BIS monitoring, patients randomly were divided into three groups. Then, anesthesia was induced by gradual increase of halothane in 50% mixture of oxygen (O(2)) and N(2)O and continued until target BIS (60 +/- 2, 50 +/- 2 and 40 +/- 2) achieved. After tracheal intubation, the duration of laryngoscopy and the presence of laryngospasm, bronchospasm, laryngoscopy failure, the movement of extremities and the changes in SpO2 and BIS were recorded. The data were analyzed by chi-square and ANOVA at 0.05 level of significance. RESULTS: BIS could not determine the appropriate level of anesthesia for tracheal intubation in this setting. There were no differences in laryngoscopy duration and the occurrence of laryngospasm, bronchospasm, laryngoscopy failure, extremity movement and awakening time among three groups. CONCLUSIONS: These results confirmed that there was no significant difference in the incidence of complications related to intubation at different BIS values (from 60 to 40) during inhalation induction, and probably to achieve an adequate or more reliable depth of anesthesia, the lower values of BIS is required. PMID- 22091307 TI - Antihyperlipidemic activities of Pleurotus ferulae on biochemical and histological function in hypercholesterolemic rats. AB - BACKGROUND: Pleurotus ferulae is an edible mushroom has been widely used for nutritional and medicinal purposes. Irrespective of the medicinal importance or therapeutic potentials of P. ferulae, there have not been studies on anti hyperlipidemic properties. Therefore, the present study investigates the effects of dietary P. ferulae fruiting bodies on plasma and feces biochemical and on the liver histological status in hypercholesterolemic rats. METHODS: Six weeks old female Sprague-Dawley albino rats were divided into three groups of 10 rats each. Then biochemical and histological examinations were performed. RESULTS: Feeding of a diet containing 5% P. ferulae fruiting bodies to hypercholesterolemic rat reduced plasma total cholesterol, triglyceride, low-density lipoprotein (LDL), total lipid, phospholipids, and LDL/high-density lipoprotein ratio by 30.02, 49.31, 71.15, 30.23, 21.93, and 65.31%, respectively. Mushroom also significantly reduced body weight in hypercholesterolemic rats. However, it had no adverse effects on plasma albumin, total bilirubin, direct bilirubin, creatinin, blood urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride, inorganic phosphate, magnesium, and enzyme profiles. Feeding mushroom increased total lipid and cholesterol excretion in feces. The plasma lipoprotein fraction, separated by agarose gel electrophoresis, indicated that P. ferulae significantly reduced plasma beta and pre-beta-lipoprotein, while increased the alpha-lipoprotein. A histological study of hepatic cells by conventional hematoxylin-eosin and oil red O staining showed normal findings for mushroom-fed hypercholesterolemic rats. CONCLUSIONS: The present study suggests that 5% P. ferulae diet supplement provides health benefits, at least partially, by acting on the atherogenic lipid profile in hypercholesterolemic rats. PMID- 22091308 TI - Evaluation of accuracy of Euroscore risk model in prediction of perioperative mortality after coronary bypass graft surgery in Isfahan. AB - BACKGROUND: This study aimed to evaluate the accuracy of Euroscore (European System for Cardiac Operative Risk Evaluation) in predicting perioperative mortality after cardiac surgery in Iranian patient population. METHODS: Data on 1362 patients undergoing coronary bypass graft surgery (CABG) from 2007 to 2009 were collected. Calibration was assessed by Hosmer-Lemeshow goodness-of-fit. Area under the curve (AUC) was used to assess score validity. Odds ratios were measured to evaluate the predictive value of each risk factor on mortality rate. RESULTS: The overall perioperative in hospital mortality was 3.6% whereas the Euroscore predicted a mortality of 3.96%. Euroscore model fitted well in the validation databases. The mean AUC was 66%. Mean length of intensive care unit (ICU) stay was 2.5 +/- 2.5 days. Among risk factors, only left ventricular dysfunction, age and neurologic dysfunction were found to be related to mortality rate. CONCLUSIONS: Euroscore did not have acceptable discriminatory ability in perioperative in hospital mortality in Iranian patients. It seems that development of a local mortality risk scores corresponding to our patients epidemiologic characteristics may improve prediction of outcome. PMID- 22091309 TI - The effect of psychiatric symptoms on the internet addiction disorder in Isfahan's University students. AB - BACKGROUND: Internet addiction disorder is an interdisciplinary phenomenon and it has been studied from different viewpoints in terms of various sciences such as medicine, computer, sociology, law, ethics, and psychology. The aim of this study was to determine the association of psychiatric symptoms with Internet addiction while controlling for the effects of age, gender, marital status, and educational levels. It is hypothesized, that high levels of Internet addiction are associated with psychiatric symptoms and are specially correlated with obsessive-compulsive disorder symptoms. METHODS: In a cross-sectional study, a total number of 250 students from Isfahan's universities were randomly selected. Subjects completed the demographic questionnaire, the Young Diagnostic Questionnaire (YDQ) and the Symptom Checklist-90-Revision (SCL-90-R). Data was analyzed using the multiple logistic regression method. RESULTS: There was an association between psychiatric symptoms such as somatization, sensitivity, depression, anxiety, aggression, phobias, and psychosis with exception of paranoia; and diagnosis of Internet addiction controlling for age, sex, education level, marital status, and type of universities. CONCLUSIONS: A great percentage of youths in the population suffer from the adverse effects of Internet addiction. It is necessary for psychiatrists and psychologists to be aware of the mental problems caused by Internet addiction. PMID- 22091310 TI - Association between sleep duration and metabolic syndrome in a population-based study: Isfahan Healthy Heart Program. AB - BACKGROUND: Recent epidemiologic studies have found that self-reported sleep duration is associated with components of metabolic syndrome (MS) such as obesity, diabetes and hypertension. This relation may be under influence of regional factors in different regions of the world. The association of sleep duration and MS in a sample of Iranian people in the central region of Iran was investigated in this study. METHODS: This cross-sectional study was conducted as a part of the Isfahan Healthy Heart Program (IHHP). A total of 12492 individuals aged over 19 years, 6110 men and 6382 women entered the study. Definition of National Cholesterol Education Program was used to define MS. Sleep duration was reported by participants. Relation between sleep duration with MS was examined using categorical logistic regression in two models; unadjusted and adjusted for age and sex. RESULTS: In our study, 23.5 % of participants had MS. Compared with sleep duration of 7-8 hours per night; sleep duration of less than 5 hours was associated with a higher odds ratio for MS. This association remained significant even after adjustment for age and sex (OR: 1.52; 95%CI: 1.33-1.74). However, sleep duration of 9 hours or more showed a protective association with MS (OR: 0.79; 95%CI: 0.68-0.94). CONCLUSIONS: There was a positive relation between sleep deprivation and MS and its components. This relation was slightly affected by sex and age. PMID- 22091311 TI - DNA-methyltransferase 3B 39179 G > T polymorphism and risk of sporadic colorectal cancer in a subset of Iranian population. AB - BACKGROUND: Epigenetic event is a biological regulation that influences the expression of various genes involved in cancer. DNA methylation is established by DNA methyltransferases, particularly DNAmethyltransferase 3B (DNMT3B). It seems to play an oncogenic role in the creation of abnormal methylation during tumorigenesis. The polymorphisms of the DNMT3B gene may influence DNMT3B activity in DNA methylation and increase the susceptibility to several cancers. These genetic polymorphisms have been studied in several cancers in different populations. METHODS: In this study, we performed a case-control study with 125 colorectal cancer patients and 135 cancer-free controls to evaluate the association between DNMT3B G39179T polymorphism (rs1569686) in the promoter region and the risk of sporadic colorectal cancer. Up to now, few studies have investigated the role of this gene variant in sporadic colorectal cancer with no familial history. The genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. RESULTS: We found that compared with G allele carriers, statistically the DNMT3B TT genotype (%34) was significantly associated with increased risk of colorectal cancer (adjusted OR, 3.993, 95% CI, 1.726-9.238, P = 0.001). Compared with DNMT3B TT genotype, the GT and GG genotypes had lower risk of developing sporadic colorectal cancer (OR = 0.848, 95% CI = 0.436-1.650). CONCLUSIONS: Our findings were consistent with that of previously reported case-control studies with colorectal cancer. These results suggest that the DNMT3B G39179T polymorphism influences DNMT3B expression, thus contributing to the genetic susceptibility to colorectal cancer. Further mechanistic studies are needed to unravel the causal molecular mechanisms. PMID- 22091312 TI - Primary bone lymphoma: a clinicopathological retrospective study of 28 patients in a single institution. AB - BACKGROUND: Primary bone lymphoma (PBL) is a rare disease and distinct clinicopathological entity. The optimal treatment strategy is still unclear. Because of rarity of PBL, we report our institute experience in PBL clinicopathological feature and treatment results. METHODS: 28 patients diagnosed with PBL were referred to Omid Hospital, cancer research center (CRC), between March 2001 and February 2009. Immunophenotype studies on 16 out of 28 pathological blocks were performed. We analyzed disease free survival (DFS) and overall survival (OS) rates. RESULTS: 14 patients with PBL were analyzed retrospectively. 17 patients (60.7%) were male and 11 (39.3%) were female with a median age of 41 years (range: 11-79). Long bones were the most primarily site of involvement (71%). 26 (93%) patients had diffuse large B cell lymphoma and 2 (7%) had small lymphoblastic lymphoma. One (3%) patient received radiation alone, 18 (66%) cases received combined modality (chemotherapy + radiotherapy) and 8 (30%) received only chemotherapy during their treatment period. The median follow up was 18 months (range: 1-82). Mean DFS was 51 months (range: 37-66). Overall survival (OS) was 54 months (range: 40-68). OS was significantly better in the chemoradiotherapy group compared with other two groups (64 versus 27 months, respectively, p=0.014). DFS was also significantly better in combined modality arm compared with other two groups (64 versus 21 months, respectively, p=0.003). CONCLUSIONS: In spite of small number of patients reported in this study, combined modality treatment (chemotherapy and radiotherapy) was shown to be useful as an effective treatment strategy in PBL. PMID- 22091313 TI - Prevalence of underweight, overweight and obesity in preschool children of Tehran, Iran. AB - BACKGROUND: It is reported that prevalence of overweight and obesity have increased in all age groups, but little is known about prevalence of overweight and obesity in preschool children. Therefore, the purpose of this study was to survey the prevalence of underweight, overweight and obesity in 3-6 year-old Tehranian children in 2009-2010. METHODS: This cross-sectional study was performed on a total of 756 (378 boys and 378 girls) preschool children aged 3-6. Subjects were selected through stratified sampling from 5 geographic regions of Tehran (east, west, north, south, and center). Body weight and height were measured directly. Underweight, overweight and obesity was defined as Body Mass Index (BMI) <= 5(th) percentile (underweight), 5(th) to 85(th) percentile (normal weight), 85(th) to 95(th) percentile (overweight), and > 95(th) percentile (obesity); based on recommendation of Centers for Disease Control (CDC) in 2000. RESULTS: Findings showed that the prevalence of underweight, overweight and obesity was 4.77%, 9.81% and 4.77% in boys and 4.77%, 10.31% and 4.49% in girls, respectively. CONCLUSIONS: Our findings showed a relatively high prevalence of overweight and obesity in Tehranian preschool children that is a serious problem. This result can be used in clinical setting and preventive programs. PMID- 22091314 TI - Anesthesia in multiple sclerosis and obstructive sleep apnea: case report and literature review. AB - While patients with obstructive sleep apnea (OSA) or multiple sclerosis (MS) are at high risk of developing postoperative complications, both of them have special anesthetic considerations in intraoperative and postoperative periods. A careful preoperative evaluation, use of the optimal anesthetic regimen and close postoperative care is essential for these patients. Rarity of coexistence of both obstructive sleep apnea and multiple sclerosis in a surgical patient necessitates careful anesthetic management. We here report anesthetic management of a female patient with OSA and MS who underwent anesthesia three times for surgery and review the literature. PMID- 22091315 TI - A case report of Gorlin-Goltz syndrome as a rare hereditary disorder. AB - Gorlin-Goltz syndrome is an autosomal dominant and a rare hereditary disease. Diagnosis of this syndrome is based on major and minor criteria. We report a Gorlin-Goltz syndrome in a 25-year-old male who was presented with progressive pain of maxilla and mandible over 5 years. The pain was diffuse and compatible with expansile cyst in alveolar ridges on panoramic radiography. In physical examination, he had coarse face and prognathism. Computer tomography of face revealed two expansile maxillary and one mandibular cyst. Calcification of entire length in falx and tentorium were detected in bone window. PMID- 22091316 TI - Ossifying fibroma of the ethmoid sinus: Report of a rare case and review of literature. AB - Ossifying fibroma (OF) is a benign fibro-osseous lesion which was first described by Menzel in 1872. It is commonly seen in the head and neck regions and represents an aggressive pattern when the midface and paranasal sinuses are involved. We report a 36 years old white woman with OF in the right ethmoid sinus. Computed Tomography (CT) scan images showed a hyperdense mass. Transnasal endoscopic resection was performed and histopathological examination confirmed the diagnosis of OF. The present case is notable because involvement of the ethmoid sinus is rare in this condition with only 48 cases reported in the literature until June 2011. PMID- 22091317 TI - Treatment of Lymphedema Praecox through Low Level Laser Therapy (LLLT). AB - A 15-year-old girl with right lower extremity lymphedema praecox was treated through Low Level Laser Therapy (LLLT), by means of a GaAs and GaAlAs diodes laser-therapy device. Treatment sessions were totally 24, each cycle containing 12 every other day 15-minute sessions, and one month free between the cycles. The treatment was achieved to decrease the edema and no significant increase in circumference of involved leg was found following three months after the course of treatment. Although LLLT can be considered a beneficial treatment for Lymphedema Praecox, any definite statement around its effectiveness needs more studies on more cases. PMID- 22091318 TI - Knowledge and practice in association with self-medication of nutrient supplements, herbal and chemical pills among women based on Health Belief Model. PMID- 22091319 TI - Post-coupling strategy enables true receptor-targeted nanoparticles. AB - A key goal of our research is the targeted delivery of functional biopharmaceutical agents of interest, such as small interfering RNA (siRNA), to selected cells by means of receptor-mediated nanoparticle technologies. Recently, we described how pH-triggered, PEGylated siRNA-nanoparticles (pH triggered siRNA ABC nanoparticles) were able to mediate the passive targeting of siRNA to liver cells in vivo. In addition, PEGylated siRNA nanoparticles enabled for long-term circulation (LTC siRNA-ABC nanoparticles, LEsiRNA nanoparticles) were shown to do the same to tumour cells in vivo. Further gains in the efficiency of siRNA delivery are expected to require active targeting with nanoparticles targeted for delivery and cellular uptake by means of attached biological ligands. Here we report on the development of a new synthetic chemistry and a bioconjugation methodology that allows for the controlled formulation of PEGylated nanoparticles which surface-present integrin-targeting peptides unambiguously and so enable integrin receptor-mediated cellular uptake. Furthermore, we present delivery data that provide a clear preliminary demonstration of physical principles that we propose should underpin successful, bonefide receptor-mediated targeted delivery of therapeutic and/or imaging agents to cells. PMID- 22091320 TI - Refinement on surgical technique: role of magnification. PMID- 22091321 TI - Abdominal Wall Reconstruction Using De-epithelialized Dermal Flap: A New Technique. AB - BACKGROUND: Although autogenous materials have been used in abdominal wall hernioplasty for a long time, the introduction of prosthetic materials diminished their popularity. However, these materials may be expensive, inappropriate or unavailable. The aim of this study is to determine the place of de-epithelialized dermal flap in the reconstruction of abdominal wall hernias. MATERIALS AND METHODS: A five-year prospective, descriptive analysis of eligible patients with difficult abdominal wall hernias closed with de-epithelialized dermal flap in a Nigerian Tertiary Health Institution, from January 2001 to December 2005. RESULTS: Over the five-year period, 37 patients were recruited into the study. There were 11 males and 26 females, giving a male: female ratio of 1: 2.4. The ages ranged from 8 months to 47 years (mean = 12.6 years). The defects consisted of 15 incisional hernias, 12 intermuscular/inferior lumbar hernias, nine healed exomphalos major and two giant umbilical hernias. The size of the hernia defects ranged from 4.5 cm to13cm (mean = 6.4 cm). Three patients had bowel resection and end-to-end anastomosis, in addition to the flap reconstruction. Morbidity was minimal and included skin dimpling in 11 patients, seroma in three, and wound infection in two patients. Neither recurrence of herniation nor mortality was recorded during the period of follow-up, which ranged from three months to 4.5 years (mean = nine months). CONCLUSION: The results suggest that this is a useful technique that can easily be applied in many centers with minimal resources. It is cheap, effective and associated with minimal morbidity. PMID- 22091322 TI - Hip Hemiarthroplasty for Femoral Neck Fractures Using the Modified Stracathroc approach - Short Term Results in Twenty-six Patients. AB - BACKGROUND AND OBJECTIVE: The Stracathro approach to the hip is a modification of the lateral approach, which was popularized by Hays and McLauchlan. It has a high safety profile and a low rate of hip dislocation. However, the need for osteotomy increases blood loss, risk of intraoperative fracture, and postoperative heterotopic calcification. In sub-Saharan Africa, where traditional healers dabble in the treatment of all musculoskeletal conditions, extensive soft tissue contractures and disuse osteoporosis arise and further complicate the lateral approach. The objective of this article is to highlight modifications made to the stracathro approach and present the short-term results in a group of 26 patients, who had hemiarthroplasty using this technique. MATERIALS AND METHODS: All patients presenting with subcapital or transcervical fracture of the femoral neck after the age of 50 years were offered hemiarthroplasty using the modified Stracathro approach, with follow-ups for a period ranging from 28 - 84 months. RESULTS: A majority (23 out of 26 - 88.5%) of patients presented late for the treatment, due to the patronage of traditional bonesetters. In spite of the soft tissue contractures and osteoporosis associated with late presentation, there was no case of intraoperative fractures. The patients had good hip abduction postoperatively. In addition, there was no intraoperative nerve or vascular injury. CONCLUSION: The short-term results in this group of patients showed that the modified Stracathro approach was safe and useful in hemiarthroplasty, for patients with soft tissue contracture and osteoporosis. PMID- 22091323 TI - Using 'Catheter a Fentes' for Management of Childhood Hydrocephalus: A Prospective Study of Ninety-six Cases. AB - OBJECTIVE: To evaluate the management of childhood hydrocephalus using the 'catheter a fentes' as a ventriculoperitoneal shunt. MATERIALS AND METHODS: A prospective study from January 2003 to January 2004 was carried out in the Neurosurgery Department of the National Hospital Niamey (Niger-Republic). Ninety six infants with hydrocephalus, between the ages of 1 to 22 months were treated with 'catheter a fentes' as a ventriculoperitoneal shunt. RESULTS: Ninety-six infants with hydrocephalus, between the ages of 1 and 22 months were included in this study, over a period of 31 months; 53% of the infants were females. The symptoms evolved over three months in 89.55% of the cases (n = 85). Hydrocephalus was post-infective in 51% of the cases, associated with spina bifida in 32% of the cases, neonatal bleeding in 7.2% of the cases; brain abnormalities were found in 6.2%, and tumor in 3.1% of the cases. The head circumference was greater than 2SD in all cases; 87.53% of the infants had psychomotor retardation (less than 80 QD according to the Lezine score). Ventricular dilation was triventricular in 17.70% and tetra ventricular in 82.29% of the cases. 'Catheter a fentes' models of high pressure, medium pressure, and low pressure were used. Hydrodynamic complications (hyperdrainage, obstruction, underdrainage) occurred in 7.9% of the cases, and these were handled with simple observation in follow-up clinics. The average regression of head circumference three months postoperatively, for all the three models of 'catheter a fentes,' was 3.73 cm. CONCLUSION: This study shows that the usage of 'catheter a fentes' for treatment of childhood hydrocephalus gives satisfactory results. PMID- 22091324 TI - The level of fibula osteotomy and incidence of peroneal nerve palsy in proximal tibial osteotomy. AB - OBJECTIVES: The level of fibular osteotomy has a role in the incidence of peroneal nerve palsy (PNP). This study aims to compare the prevalence of PNP among patients who had fibular osteotomy at two different levels. MATERIALS AND METHODS: Sixty-nine limbs in fifty-two patients had valgus osteotomy of the proximal tibia and fibular osteotomy at two different levels - the proximal half (Group 1) and distal half (Group 2). The results of these were compared. RESULTS: The incidence of peroneal nerve palsy was 23.6 and 3.2% in Groups 1 and 2, respectively (P < 0.025). CONCLUSION: This study supports the choice of the distal half for fibular osteotomy. PMID- 22091325 TI - Pentalogy of cantrell: a report of three cases. AB - Pentalogy of Cantrell is a rare upper midline syndrome that may present in association with anomalies outside the torso. The pentad - the supraumbilical body wall defect, sternal defect, deficiency of the anterior diaphragm, defect of the diaphragmatic pericardium, and the intracardiac anomalies - was first described by Cantrell et al., in 1958. The defect is said to be more common in males, and survival is dependent on the cardiac malformations and on the degree of completeness of the syndrome. We report three cases of Cantrell's pentalogy managed in our unit. Two of the patients were females and one a male. All were seen at peripheral health centers before being referred to us. Age at presentation for the girls was 18 hours and 36 hours, respectively, the boy presented at the age of six weeks. All of their parents were unschooled manual workers. All patients presented with a defect in the supraumbilical body wall, bifid sternum, and a visible cardiac impulse. We were unable to do echocardiography to rule out intracardiac anomalies in the three patients. The thin membranous covering of the epigastrium in the female patients was managed conservatively. Both female patients were discharged against medical advice as requested by their parents, due to financial constraints. The male patient was lost to follow up after two clinic visits. A multidisciplinary approach to the management of this syndrome is recommended. PMID- 22091326 TI - Solitary giant neurofibroma of the scalp with calvarial defect in a child. AB - Neurofibroma of the scalp are mostly multiple as part of neurofibromatosis or other phakomatosis. De novo solitary types are less common and rarely erode the skull, unlike the intracranial counterpart. Skull erosion has been reported in adults with longstanding plexiform neurofibromas. We report a giant neurofibroma on the scalp of a five-year-old boy, managed in our center. Although this condition is a rare entity, it should be anticipated and the treatment strategy should include repair of the skull defect. PMID- 22091327 TI - Rachipagus: a report of two cases - thoracic and lumbar. AB - We present two cases of rachipagus in two male infants and review the literature on this anomaly. These infants were from consanguineous marriages and cases of twins were reported in their families. In the first case it was a limb attached to the lower lumbar region with a rudimentary posterior arch. At the junction there was a lipomeningocele. Anatomical dissection of the limb identified the bones of the lower limb. In the second case, the parasites were joints of the upper limb that were attached to the chest by rudimentary posterior arches. In both cases there was only one spinal canal and a single spinal cord. Except the spina bifida in the first case no other malformation was diagnosed. The parasites were successfully excised. The two patients are well at one year of follow-up. Rachipagus is a rare embryogenic malformation with a good prognosis in the absence of associated congenital anomalies. PMID- 22091328 TI - Unusual giant prostatic urethral calculus. AB - Giant vesico-prostatic urethral calculus is uncommon. Urethral stones rarely form primarily in the urethra, and they are usually associated with urethral strictures, posterior urethral valve or diverticula. We report a case of a 32 year-old man with giant vesico-prostatic (collar-stud) urethral stone presenting with sepsis and bladder outlet obstruction. The clinical presentation, management, and outcome of the giant prostatic urethral calculus are reviewed. PMID- 22091329 TI - Giant retroperitoneal lipoma in an infant. AB - Retroperitoneal lipomas have remained the essentially rare tumors seen in clinical practice. The tumors are rarer in children, with very few reported cases in surgical literature worldwide. We are reporting the case of a six-month-old child who presented with a giant retroperitoneal lipoma that was successfully managed by complete excision. There has been no recurrence noticed during follow up. PMID- 22091330 TI - Unusual cutaneous metastatic follicular thyroid carcinoma. AB - Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer (TCs) after papillary carcinoma, but it is ranked first in producing distant metastases among TCs. It accounts for 10 - 20% of all thyroid malignancies and is most often seen in patients over 40 years of age. Distant metastases at the time of diagnosis are reported in 11 - 20% of the patients and may be the reason for presentation. There have been less than 30 reported cases of cutaneous metastases from FTC in the English Literature, a majority affecting the scalp. We present an unusual aggressive, hypervascular FTC in a 58-year-old man with a previous diagnosis of multinodular goiter. The difficulty in gaining his acceptability of orthodox management resulted in the development of multiple giant scalp and right facial metastatic masses associated with lytic calvarial destruction and the involvement of frontal and right maxillary sinuses. These imposed serious challenges in managing him in a resource-poor community. PMID- 22091331 TI - Mayer-rokitansky-kuster-hauser syndrome: surgical management of two cases. AB - The Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome is a rare anomaly characterized by congenital aplasia of the uterus and vagina in women showing normal development of secondary sexual characters and normal 44 XX karyotype. We report our experience in the management of two patients with congenital absence of the vagina due to the MRKH syndrome. The first case was a 24-year-old student, who presented with primary amenorrhea, uterovaginal agenesis, right pelvi ureteric junction obstruction, and left renal agenesis. The second patient was a 24-year-old housewife, who presented with primary amenorrhea and inability to achieve penetrative sexual intercourse. She had vaginal atresia and a grossly hypoplastic uterus. Both had successful sigmoid colovaginoplasty and are sexually active. Vaginal reconstruction using the sigmoid colon saw an immediate and satisfactory outcome in both patients. PMID- 22091332 TI - The use of cyanoacrylate in surgical anastomosis: an alternative to microsurgery. AB - To present anastomosis with cyanoacrylate as a cheap, simple, fast, and available technique for anastomosis in urological, vascular, gynecological, and general surgical procedures. This method may in the future be a good alternative to microsurgery, particularly in centers where facilities are unavailable and the financial implication is unbearable for the patient. Cyanoacrylate is an adhesive or glue that is available in different chemical forms ranging from ethylcyanoacrylate (superglue) to Isobutylcyanoacrylate and octylcyanoacrylate (dermerbond), which is in clinical use. Anastomosis with cyanoacrylate requires the application of stay sutures, a luminal stent and the subsequent application of the adhesive. The adhesives with lower molecular weights produce a rigid and patent region of anastomosis, while the higher molecular compounds produce a consistency close to the normal tissue. This technique presents a surgical method that is socially, culturally, and ethically acceptable, which is affordable to a larger majority of patients in our subregion. Cyanoacrylate anastomosis may in the future present a fast, convenient, simple, and affordable option in the treatment of patients requiring anastomosis. In our subregion where the socio cultural, psychological, and economic burden of failed anastomosis is high, associated with the low per capital income, this may be a novel option for the management of urogynecological, vascular, neurosurgical, and general surgical procedures requiring either microscopic or macroscopic anastomosis. PMID- 22091333 TI - Endoscopic and external surgical approach to paranasal sinus mucocele. AB - Mucoceles of the paranasal sinuses are not common, but usually present as cystic lesions causing facial asymmetry requiring surgery. Hitherto surgical attempts at excision were external surgical approaches with the use of stents to drain the frontoethmoidal sinus, if they were the principal sinus involved, for a variable period. Recent advances in endoscopic sinus surgery have made the endoscopic approach to surgically manage paranasal sinus mucoceles the new trend. A total of 18 patients were seen over a ten-year period with paranasal sinus mucocele; 14 cases were managed through the external approach, while four were consecutively managed endoscopically. The endoscopic approach in the surgical management of mucoceles of the paranasal sinuses and the external approach are discussed in this article with the intent of showing the advantages of the two approaches, with more emphasis on the endoscopic approach and caution that should the endoscopic approach prove difficult, reversal to the external approach should be undertaken immediately, so as to avoid unnecessary complications. PMID- 22091334 TI - Clinicopathological relationship between fibrocystic disease complex and breast cancer: a case report. PMID- 22091335 TI - The advantages of lateral tarsal strip procedure. PMID- 22091336 TI - The correction of involutional entropion of eyelid by lateral strip procedure. AB - AIM: To determine cosmetic and functional outcome following lateral strip procedure (LSP) for involutional entropion. MATERIALS AND METHODS: This study was a prospective analysis of 15 patients (20 eyelids) of involutional entropion, who needed surgical repair. After thorough evaluation, the surgical treatment (LSP) was done in all 15 patients. RESULTS: Cosmetic and functional outcome was excellent in all cases following LSP. No complications and recurrence were encountered in any case. CONCLUSIONS: LSP is simple, physiologic, easy and quick to perform as OPD procedure for involutional entropion under local anesthesia without hospitalization by a general ophthalmologist. PMID- 22091337 TI - Peri-vesical fat interposition flap reinforcement in high vesico-vaginal fistulas. AB - BACKGROUND AND AIM: The urinary bladder becomes small, contracted and is associated with excess pelvic fat in long standing cases of vesico-vaginal fistulas (VVFs). The aim of this new technique was to use this excess pelvic fat for harvesting an interposition flap. MATERIALS AND METHODS: An interposition flap of peri-vesical fat was raised from the anterior, superior and posterior surfaces of the urinary bladder and was interposed between the right angle closed vaginal vault and the urinary bladder to strengthen the repair. This technique was used in two patients of VVFs. RESULTS: Both the patients had successful outcome and were able to retain sufficient quantity of urine at 3 months follow up. CONCLUSIONS: Peri-vesical fat flap proved an effective interposition flap in the repairs of VVFs in selected cases. PMID- 22091338 TI - Reverse Transrectal Stapling Technique Using the EEA Stapler: An Alternative Approach in Difficult Reversal of Hartmann's Procedure. AB - The introduction of circular end-to-end stapling devices (CEEA OR EEA stapler) into colorectal surgery have revolutionised anastomotic techniques. The EEA stapler is generally regarded as an instrument that is safe, reliable, and simple to operate. Despite it's popularity, very little information is available regarding the technical difficulties encountered during surgery. The routine technique to perform an end-to-end circular colonic anastomosis is to introduce the instrument distally through the anus (transrectal/transanal approach) and attach it to the anvil which is purse stringed at the distal end of the proximal bowel to be anastomosed. Two cases of reversal of Hartmann's procedure for perforated diverticulitis are described in the present study, where difficulty was experienced while using the EEA stapler in the routine method. Hence, an alternative reverse technique which was used is presented. PMID- 22091339 TI - Spontaneous recanalization of complete internal carotid artery: a clinical reminder. AB - Spontaneous recanalization of atherothrombotic extracranial cerebral arteries is rare vis-a-vis recanalization of intracranial vessels. The time course is unknown. The question is the advisability and timing of surgery in a recanalized vessel. We describe a patient with spontaneous recanalization of a totally occluded left Internal Carotid Artery (ICA) who was monitored with periodic imaging and in time had partial recanalization of the ICA. We believe patients with total ICA occlusion with return of function should be followed up with periodic carotid ultrasound, Magnetic Resonance Angiography (MRA) or CT angiography, and when appropriate, be candidates for carotid vascular interventions. PMID- 22091340 TI - Tuberculosis verrucosa cutis developing over a keloid: a rare presentation. AB - Cutaneous tuberculosis can present as either primary or secondary infection, or it can be associated with systemic tuberculosis. It can present with unusual clinical and histological features causing delay in diagnosis and treatment. Tuberculosis verrucosa cutis occurs as a single verrucous lesion over exposed areas of the body along with inflammatory borders and discharging sinus. Here, we are presenting a rare case of tuberculosis verrucosa cutis developing over a keloid. There is no report of such case in literature so far. PMID- 22091341 TI - Fetus-in-fetu: A Rare Congenital Anomaly. AB - Two cases of fetus-in-fetu, on which we performed surgery in 2003 and 2006, are being reported. Both the cases presented with a lump in the abdomen. Radiology confirmed the diagnosis. The lumps were found in the retroperitoneum and successfully excised. Because of the rarity of the condition, these two cases are being reported with relevant salient features and are discussed in the light of available literature. PMID- 22091342 TI - Plexiform neurofibroma: a rare tumor of submandibular salivary gland. AB - A 15-year-old boy presented with swelling in the submandibular region. X-ray of the swollen part showed faint radio opaque shadow. A provisional diagnosis of sialadenitis with sialolithiasis was made. Excised mass was reported histopathologically as plexiform neurofibroma of submandibular salivary gland.Plexiform neurofibroma of the salivary gland is a rare benign tumor often present in the parotid gland. It is very rare in submandibular salivary gland. It is a slow growing, locally infiltrating tumor. PMID- 22091343 TI - Imperforate hymen presenting as acute urinary retention in a 14-year-old nigerian girl. AB - Acute urinary retention in adolescent females is rare, just like imperforate hymen. We present a case of acute urinary retention secondary to imperforate hymen in a 14-year-old Nigerian girl. Its diagnosis and treatment are discussed with a brief review of literature. We highlight the need for a thorough evaluation in the female patient presenting with acute urinary retention, and also the need to provide better health facilities in rural areas in developing countries such as ours. PMID- 22091344 TI - Extensive supratentorial hemorrhages following posterior fossa meningioma surgery. AB - Remote supratentorial hematoma soon after posterior fossa surgery for the removal of a space-occupying lesion is a rare but dramatic and dreaded complication, carrying significant morbidity and mortality. A 47-year-old woman presented with headache of 1-year duration that worsened over last 2 months, progressive ataxia of 2 months' duration, blurring and diminution of vision of 2 months' duration and forgetfulness of 2 months' duration. Fundus showed bilateral papille dema, and visual acuity was 6/9 in both eyes. She had left-sided cerebellar signs. There were no focal motor or sensory neurological deficits. MRI brain with contrast showed a large posterior fossa tumor with obstructive hydrocephalus. The patient underwent left paramedian suboccipital craniectomy in prone position with left side up. In the immediate postoperative period, the patient did no recover from anesthesia and was persistently drowsy. Immediate repeat CT scan showed diffuse subarachnoid hemorrhage spread all over the bilateral cerebral hemispheres with diffuse cerebral edema. The patient recovered with conservative management without deficits. This case stresses the importance of early postoperative CT scan and optimal management of the hemorrhage for good outcome. PMID- 22091345 TI - Bilateral biconvex frontal chronic subdural hematoma mimicking extradural hematoma. AB - Chronic subdural hematoma (CSDH) is one of the most common clinical entities encountered in daily neurosurgical practice. The advent of computed tomography (CT) has made a major impact on the radiological diagnosis of CSDH. Although unilateral chronic isodense subdural hematomas as a result of indirect signs of a space-occupying lesion are easily recognizable on CT, bilateral CSDH may cause considerable difficulty, particularly when it is biconvex in shape as discussed in the present case. A judicious use of magnetic resonance imaging will help in making the diagnosis and for the management of such lesions. PMID- 22091346 TI - Surgicel as an unusual cause of prolonged drainage. PMID- 22091347 TI - Oral biopsy: a dental gawk. PMID- 22091348 TI - Biological characterization of Bothrops marajoensis snake venom. AB - This study describes the effects of Bothrops marajoensis venom (Marajo lancehead) on isolated neuromuscular preparations of chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND). At low concentrations (1ug/ml for CBC and 5ug/ml for PND), the venom exhibited a neuromuscular blocking without any damaging effect on the muscle integrity. At higher concentration (20MUg/ml for PND), together with the neuromuscular blockade, there was a moderate myonecrosis. The results show differences between mammalian and avian preparations in response to venom concentration; the avian preparation was more sensitive to venom neurotoxic effect than the mammalian preparation. The possible presynaptic mechanism underlying the neuromuscular blocking effect was reinforced by the observed increase in MEPPs at the same time (at 15min) when the facilitation of twitch tension occurred. These results indicate that the B. marajoensis venom produced neuromuscular blockade, which appeared to be presynaptic at low concentrations with a postsynaptic component at high concentrations, leading to muscle oedema. These observations demand the fractionation of the crude venom and characterization of its active components for a better understanding of its biological dynamics. PMID- 22091349 TI - Purification of a phospholipase A(2) from Daboia russelii siamensis venom with anticancer effects. AB - Venom phospholipases A2 (PLA(2)) are associated with neurotoxic, myotoxic, cardiotoxic, platelet aggregation, and edema activities. A PLA(2) (Drs-PLA(2)) was purified from Daboia russelii siamensis venom by a two-step purification procedure consisting of size-exclusion, followed by anion exchange high performance liquid chromatography (HPLC). The molecular weight of the Drs-PLA(2) was 13,679Da, which was determined by MALDI-TOF mass spectrometry. Its N-terminal amino acid sequence was homologous to basic PLA(2)s of viperid snake venoms. The Drs-PLA(2) had indirect hemolytic and anticoagulant activities, cytotoxic activity with a CC(50) of 65.8nM, and inhibited SK-MEL-28 cell migration with an IC(50) of 25.6nM. In addition, the Drs-PLA(2) inhibited the colonization of B16F10 cells in lungs of BALB/c mice by ~65%. PMID- 22091351 TI - Laparoscopic treatment of a rare right diaphragmatic rupture with small bowel herniation after blunt thoracic trauma. AB - Blunt traumatic diaphragmatic rupture (BTDR) is a life-threatening condition with an incidence from 0,8%-1,6% in blunt trauma, mostly located on the left side. The main prognostic factors are severe side injuries and the delay of diagnosis. We present a rare case of a 68-year-old female, with an isolated right diaphragm rupture. The diagnosis was done with a delay of 4 days by thoracic radiographs, which showed a herniation of small bowel into the right thoracic cavity. A reposition of the small bowel and a closure of the diaphragmatic defect by running suture were carried out laparoscopicly. Although large prospective studies concerning the outcome of laparoscopic approach to right BTDR are still missing, we could show, that laparoscopy can be performed safely in right traumatic diaphragm rupture. PMID- 22091350 TI - Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum. AB - The notion that breast cancers can survive in an individual patient in a dormant state only to grow as metastatic disease in the future, is in our view incontrovertibly established. Convincing too is the evidence that surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. Accepting that many deaths due to breast cancer might be averted were we to understand the cellular mechanisms underlying escape from dormancy, we have examined the extracellular signals produced by breast cancers derived from women with metastatic breast disease. In this perspective, we explore the role of extracellular nucleotide signaling that we have proposed constitutes a pathological axis from the transformed tumor cell to the endothelium in the service of intravasation, dissemination, extravasation and angiogenesis. A role for the dinucleotide kinase NM23/NDPK (nucleoside diphosphate kinase) secreted by breast tumor cells in the generation of signals that stimulate vascular leakiness, anti-thrombosis, endothelial migration and growth, constitutes a mechanistic basis for escape from latency and offers putative therapeutic targets for breast cancer management not previously appreciated. PMID- 22091352 TI - The Relationship between Tests of Neurocognition and Performance on a Laparoscopic Simulator. AB - Objective. To estimate if there is a relationship between the results of tests of neurocognition and performance on a laparoscopic surgery simulator. Methods and Materials. Twenty participants with no prior laparoscopic experience had baseline cognitive tests administered (Trail Making Test, Part A and B (TMT-A and TMT-B), Grooved Peg Board Test, Symbol Digit Modalities Test, Symbol Digit Recall Test, and Stroop Interference Test), completed a demographic questionnaire, and then performed laparoscopy using a simulator. We correlated the results of cognitive tests with laparoscopic surgical performance. Results. One cognitive test sensitive to frontal lobe function, TMT-A, significantly correlated with laparoscopic surgical performance on the simulator (correlation coefficient of 0.534 with P < .05). However, the correlation between performance and other cognitive tests (TMT-B, Grooved Peg Board Test, Symbol Digit Modalities Test, Symbol Digit Recall Test, and Stroop Interference Test) was not statistically significant. Conclusion. Laparoscopic performance may be related to measures of frontal lobe function. Neurocognitive tests may predict motor skills abilities and performance on laparoscopic simulator. PMID- 22091353 TI - Laparoscopic cholecystectomy combined using miniaturised instruments in transgastric gall bladder removal: performed on 63 patients. AB - Background. The laparoscopic cholecystectomy is a perfectly codified surgical procedure. The development of recent innovative and experimental surgical techniques Natural Orifice transluminal endoscopic surger (N.O.T.E.S.) which reduces the abdominal wall trauma leads us to develop a combined procedure of a standard dissection using miniaturised instruments already existing on the market (3 and 5 mm wide) and a gall bladder removal through a short gastrotomy Natural Orifice Specimen Extraction (N.O.S.E.). Methods. Our objective was to evaluate the safety, the feasibility, and the reproducibility of our new approach. After reviewing existing products on the market and a feasibility study, we put in place a protocol in our structure for patients on whom the procedure was performed. We carried out a gall bladder removal by a short gastrotomy, located on the anterior gastric wall, which then reduced the abdominal wall trauma and allowed them to resume normal physical activity quickly without risk of trocar site hernia. Results. We performed the procedure described in this paper on 63 patients, between April 2008 and July 2009. There were 14 men and 49 women with an average age of 46.8 years (ranging from 28 to 77) and an average BMI of 27.2. 30 patients had at least one gallstone larger than 10 mm. There was no postoperative gastric or abdominal wall complication and a fast recovery for all the patients in our study. Conclusions. This procedure is feasible, reproducible, with good results and minimal abdominal wall trauma. It is also safer than N.O.T.E.S. and endoscopic clipping and recovery, allowing normal physical activity, fast and, without risk of incisional hernia. PMID- 22091354 TI - The learning curve for a fetal cardiac intervention team. AB - Objectives. Multiple technical difficulties are encountered when a multidisciplinary team of subspecialists begins a minimally-invasive fetal cardiac interventional program. We describe the learning curve. Study Design. Ten pregnant sheep underwent ultrasound-guided balloon valvuloplasty of the aortic valve. Team members and their roles remained constant through the trial. The time between needle insertion and entrance of the left ventricle at the aortic root was recorded. F-test was used to assess significance (P <= .05). Results. The time required to accurately position the needle tip at the aortic root decreased significantly over the course of the trial, from 12 minutes with the first attempt to one minute with the last (P = .003). Conclusion. A significant learning curve is encountered when a multidisciplinary team begins a minimally invasive fetal cardiac intervention program. However, technical proficiency can be achieved with practice. Institutions interested in developing such a program should consider practice in an animal model before proceeding to the human fetus. PMID- 22091355 TI - Endoscopic resection and topical 5-Fluorouracil as an alternative treatment to craniofacial resection for the management of primary intestinal-type sinonasal adenocarcinoma. AB - Introduction. Intestinal-type adenocarcinoma of the sinonasal tract is very rare and is responsible for less than 4% of tumours of the sinuses. Craniofacial resection has been the mainstay of treatment for many years; however, techniques for endoscopic resection are constantly being developed. Discussion. The use of transnasal endoscopic resection (TER) and topical chemotherapy applications as an alternative to cranio-facial resection (CFR) is discussed. TER offers advantages over CFR in terms of fewer intra-operative complications and an improved cosmetic outcome. Survival and metastatic rates are similar between both procedures. Patients with locally invasive tumours are better managed with CFR. Topical applications of 5-Fluorouracil has been shown to be effective in increasing survival in patients with sino-nasal malignancy. Conclusion. Trans-nasal endoscopic resection and topical 5-Fluorouracil could potentially offer an acceptable alternative treatment to the standard of cranio-facial resection. This should be investigated in trials with a longer followup period than this paper in order to directly compare the two treatment modalities. PMID- 22091356 TI - A novel technique of uterine manipulation in laparoscopic pelvic oncosurgical procedures: "the uterine hitch technique". AB - Aim. To describe a new technique of uterine manipulation in laparoscopic management of pelvic cancers. Material and Methods. We used a novel uterine hitch technique in 23 patients from May 2008 to October 2008. These patients underwent pelvic oncologic surgery including laparoscopic radical hysterectomy (n = 7), laparoscopic anterior resection (n = 4), laparoscopic abdominoperineal resection (n = 3), laparoscopic posterior exenteration (n = 4), or laparoscopic anterior exenteration (n = 5). The uterus was hitched to the anterior abdominal.wall by either a single suture in the fundus or by sutures through the round ligaments. Results. The uterine hitch technique was successfully accomplished in all procedures. It was performed in less than 5 minutes in all cases. It obviated the need for vaginal manipulation. An extra port for retraction could be avoided. There were no intraoperative complications. Conclusion. A practical, cheap and reproducible method for uterine manipulation, during pelvic oncologic surgery is described. It improves the stability of the uterus and also obviates the need for keeping an additional assistant for vaginal manipulation in any of the procedures. PMID- 22091357 TI - Laparoendoscopic Single-Site Surgery (LESS) for a Large Ovarian Tumour: First Clinical Case Report. AB - Objective. To report the feasibility of removing a 10 cm ovarian fibroma via a laparoendoscopic single-site trocar through trans-umbilical access. Design. Case report. Setting. Teaching and research hospital. Patient. A 64-year-old patient affected by a large 10 cm ovarian tumour. Intervention(s). Bilateral salpingo oophorectomy a large 10 cm ovarian tumour, using a laparoendoscopic single-site approach with a Covidien SILS multitrocar access device and standard laparoscopic instruments. Main Outcome Measure(s). Conversion to standard laparoscopic technique or laparotomy, estimated blood loss, operative time , extent of scarring, occurrence of intra- and perioperative surgical complications, technical adequacy, and clinical outcome. Result(s). No conversion to standard laparoscopic technique or laparotomy, and no intraoperative or postoperative complications were observed. Total operative time was 99 minutes. The patient was discharged home on postoperative day one. Conclusion(s). Laparoendoscopic single site bilateral salpingo-oophorectomy of a large ovarian tumour is feasible with standard laparoscopic instruments. It is safe and effective, with good results in terms of excellent cosmesis and minimal postoperative pain. PMID- 22091358 TI - Preoperative parathyroid needle localization: a minimally invasive novel technique in reoperative settings. AB - Background. Reoperative parathyroid surgery for primary hyperparathyroidism can be challenging. Numerous preoperative localization techniques have been employed to facilitate a more focused surgical exploration. This paper describes a novel, minimally invasive, and highly successful method of parathyroid localization. Methods. Patients with recurrent or persistent primary hyperparathyroidism underwent parathyroidectomy following CT scan or ultrasound-guided wire localization of the parathyroid. Accurate placement was confirmed by fine-needle aspiration with immunocytochemistry or PTH washout. The guide wire was left in situ to guide surgical excision of the gland. Curative resection was established by monitoring intact serum PTH levels after excision of the adenoma. Results. All ten patients underwent successful redo-targeted parathyroidectomy. Nine of the ten patients were discharged on the day of surgery. One patient was observed overnight due to transient postoperative hypocalcemia, which resolved with calcium supplementation. Conclusion. Placement of a localization wire via preoperative high-resolution ultrasound or CT can expedite reoperative parathyroid surgery. It allows identification of parathyroid adenoma via a minimally invasive approach, especially in cases where a sestamibi scan is inconclusive. PMID- 22091359 TI - Single-Incision Laparoscopic Liver Resection for Colorectal Metastasis through Stoma Site at Time of Reversal of Diversion Ileostomy: A Case Report. AB - Minimally invasive surgical techniques for liver tumors are gaining increased acceptance as an alternative to traditional resections by laparotomy. In this article we describe a laparoscopic liver resection of a metastatic lesion in a patient primarily operated for colorectal cancer. The resection was conducted as a single port procedure through the stoma aperture at time of reversal of the diversion ileostomy. Sigle incision liver resections may be less traumatic than conventional laparoscopy and could be applied in selected patients with both benign and malignant liver tumors. PMID- 22091360 TI - An Effective Approach to Improving Day-Case Rates following Laparoscopic Cholecystectomy. AB - Background. Day-case laparoscopic cholecystectomy (LC) is a safe and cost effective treatment for gallstones. In 2006, our institution recorded an 86% laparoscopic, 10% day-case, and 5% readmission rate. A gallbladder pathway was therefore introduced in 2007 with the aim of increasing daycase rates. Methods. Patients with symptomatic gallstones, proven on ultrasound, were referred to a specialist-led clinic. Those suitable for surgery were consented, preassessed, and provided with a choice of dates. All defaulted to day case unless deemed unsuitable due to comorbidity or social factors. Results. The number of cholecystectomies increased from 464 in 2006 to 578 in 2008. Day-case rates in 2006, 2007, 2008, and June 2009 were 10%, 20%, 30%, and 61%, respectively. Laparoscopic and readmission rates remained unchanged. Conversion rates for elective cholecystectomy fell from 6% in 2006 to 3% in 2009. Conclusions. Development of a gallbladder pathway increased day-case rates sixfold without an associated increase in conversion or readmission rates. PMID- 22091361 TI - Percutaneous ventricular assist devices: new deus ex machina? AB - The development of ventricular assist devices has broadened the means with which one can treat acute heart failure. Percutaneous ventricular assist devices (pVAD) have risen from recent technological advances. They are smaller, easier, and faster to implant, all important qualities in the setting of acute heart failure. The present paper briefly describes the functioning and assets of the most common devices used today. It gives an overview of the current evidence and indications for left ventricular assist device use in cardiogenic shock and high-risk percutaneous coronary intervention. Finally, extracorporeal life support devices are dealt with in the setting of hemodynamic support. PMID- 22091362 TI - Arthroscopic optical coherence tomography in diagnosis of early arthritis. AB - Osteoarthritis (OA) is a progressive, debilitating disease that is increasing in prevalence. The pathogenesis of OA is likely multifactorial but ultimately leads to progressive breakdown of collagen matrix and loss of chondrocytes. Current clinical modalities employed to evaluate cartilage health and diagnose osteoarthritis in orthopaedic surgery include, radiography, MRI, and arthroscopy. While these assessment methods can show cartilage fissuring and loss, they are limited in ability to diagnose cartilage injury and degeneration prior breakdown of the articular surface. An improved clinical ability to detect subsurface cartilage pathology is important for development and testing of chondroprotective and chondrorestorative treatments because the pathological changes following surface breakdown are generally considered to be irreversible. Optical Coherence Tomography (OCT), is a novel, non-destructive imaging technology capable of near real time cross-sectional images of articular cartilage at high resolutions comparable to low power histology. This review discusses a series of bench to bedside studies supporting the potential use of OCT for enhanced clinical diagnosis and staging of early cartilage injury and degeneration. OCT was also found to be useful as a translations research tool to assist in clinical evaluation of novel quantitative MRI technologies for non-invasive evaluation of articular cartilage. PMID- 22091363 TI - Evaluation of clinical outcome after laparoscopic antireflux surgery in clinical practice: still a controversial issue. AB - Background. Laparoscopic antireflux surgery has shown to be effective in controlling gastroesophageal reflux (GERD). Yet, a universally accepted definition and evaluation for treatment success/failure in GERD is still controversial. The purpose of this paper is to assess if and how the outcome variables used in the different studies could possibly lead to an homogeneous appraisal of the limits and indications of LARS. Methods. We analyzed papers focusing on the efficacy and outcome of LARS and published in English literature over the last 10 years. Results. Symptoms scores and outcome variables reported are dissimilar and not uniform. The most consistent parameter was patient's satisfaction (mean satisfaction rate: 88.9%). Antireflux medications are not a trustworthy outcome index. Endoscopy and esophageal manometry do not appear very helpful. Twenty-four hours pH metry is recommended in patients difficult to manage for recurrent typical symptoms. Conclusions. More uniform symptoms scales and quality of life tools are needed for assessing the clinical outcome after laparoscopic antireflux surgery. In an era of cost containment, objective evaluation tests should be more specifically addressed. Relying on patient's satisfaction may be ambiguous, yet from this study it can be considered a practical and simple tool. PMID- 22091364 TI - Rectal atresia-operative management with endoscopy and transanal approach: a case report. AB - The aim of this study is to present the technique and outcome of the management of a newborn child with rectal atresia. A girl born with rectal atresia was diagnosed during physical examination and confirmed with X-ray. The anatomic appearance of the external anus, and lower pelvis was normal. The rectal ending was located 2 cm cranial from the anus and the distance between the rectal endings was 2 cm. A colostomy was established. At the age of five months the child was operated on with a rectal anastomosis using the endoscopic and transanal approach. Closure of the colostomy was performed at the age of ten months. The rectal anastomosis was treated with rectal dilatation weekly in order to avoid stricture. The patient was faecally continent at followup one and three months postoperatively. In conclusion, the endoscopic and transanal approach is an alternative to other surgical techniques in the management of rectal atresia. PMID- 22091366 TI - Arthroscopic subtalar arthrodesis after a calcaneus fracture covered with a forearm flap. AB - Surgical treatment of intraarticular calcaneal fractures is often associated with postoperative wound problems. Soft tissue necrosis, bone loss and uncontrollable infection are a challenge for the surgeon and amputation may in some cases be the ultimate solution. A free flap can be very helpful to cover a significant soft tissue defect and help in fighting the infection. However, the free flap complicates the surgical approach if subtalar arthrodesis and bone reconstruction are needed. This study demonstrates the value of an arthroscopic technique to resect the remaining articular cartilage in preparation for subtalar arthrodesis and bone grafting. This approach avoids compromising the soft tissues and minimizes damage to the free flap. PMID- 22091365 TI - Single-Incision Cholecystectomy in about 200 Patients. AB - Background and Aims. We describe our experience of performing transumbilical single-incision laparoendoscopic cholecystectomy as standard procedure for acute and chronic gallbladder diseases. Methods. Between September 2008 and March 2010, 220 patients underwent laparoscopic single-incision surgery. A single port was used for 196 patients and two conventional 5 mm and one 10 mm port in 24 cases. All operations were performed with straight instruments. Results. Single-incision surgery was successfully performed in 215 patients (98%). Three patients (1.4%) required conversion to a three-port technique and two patients (0.9%) to an open procedure. Average age of 142 women (65%) and 78 men (35%) was 47 years (range: 15-89), average ASA status 2 (range: 1-3) and BMI 28 (range: 15-49). Mean operative time was 62 minutes (range: 26-174) and 57 patients (26%) had histopathological signs of acute cholecystitis. Eleven patients (5%) developed to surgery-related complications and nine (4%) of these required a reoperation. The mean followup was 331.5 (range: 11-590) days. Conclusion. Transumbilical single incision cholecystectomy is a feasible and safe new approach for routine cholecystectomy. After a short learning curve, operation time and complication rate are comparable with standard multiport operation. In addition, most cases of acute cholecystitis can be performed with this technique. PMID- 22091367 TI - Technical progress in single-incision laparoscopic cholecystectomy in our initial experience. AB - Single-incision laparoscopic cholecystectomy (SILC) has rapidly spread throughout the world because of its low invasiveness and because it is a scarless procedure. Various surgical methods of performing SILC are present in each institute; however, it is necessary to develop a standardized procedure that we can perform safely, such as the conventional 4-port laparoscopic cholecystectomy (LC). The SILC experiment in our institute was started by use of the commercial SILS Port and changed from a 3-port method via an umbilicus to a 2-port method to improve some problems. Although none of the conversions to conventional 4-port LC and also none of the complications such as bile duct injury occurred in each method, the 2-port method functioned best and was also economical. However, it is most important to adopt strict criteria and select the patients suitable for SILC to demonstrate SILC safety same as 4-port LC. PMID- 22091369 TI - Dual-Source CT Angiography of Peripheral Arterial Stents: In Vitro Evaluation of 22 Different Stent Types. AB - Purpose. To test different peripheral arterial stents using four image reconstruction approaches with respect to lumen visualization, lumen attenuation and image noise in dual-source multidetector row CT (DSCT) in vitro. Methods and Materials. 22 stents (nitinol, steel, cobalt-alloy, tantalum, platinum alloy) were examined in a vessel phantom. All stents were imaged in axial orientation with standard parameters. Image reconstructions were obtained with four different convolution kernels. To evaluate visualization characteristics of the stent, the lumen diameter, intraluminal density and noise were measured. Results. The mean percentage of the visible stent lumen diameter from the nominal stent diameter was 74.5% +/- 5.7 for the medium-sharp kernel, 72.8% +/- 6.4 for the medium, 70.8% +/- 6.4 for the medium-smooth and 67.6% +/- 6.6 for the smooth kernel. Mean values of lumen attenuation were 299.7HU +/- 127 (medium-sharp), 273.9HU +/- 68 (medium), 270.7HU +/- 53 (medium-smooth) and 265.8HU +/- 43. Mean image noise was: 54.6 +/- 6.3, 20.5 +/- 1.7, 16.3 +/- 1.7, 14.0 +/- 2 respectively. Conclusion. Visible stent lumen diameter varies depending on stent type and scan parameters. Lumen diameter visibility increases with the sharpness of the reconstruction kernel. Smoother kernels provide more realistic density measurements inside the stent lumen and less image noise. PMID- 22091370 TI - Intraoperative three-dimensional imaging in selective decompression for lumbar spinal stenosis: a useful tool in theory but also in everyday practice? AB - Background. We conducted a pilot study to investigate the value of an Iso-C3D imaging system in determining the extent of decompression of lumbar spinal stenosis during surgery. We now address the question whether this imaging has become a routine tool. Material and Methods. Ten patients who underwent unilateral decompression for lumbar spinal stenosis were intraoperatively examined using the Iso-C3D imaging system. Four years after this study, we investigated whether this intraoperative imaging modality is still being used. Results. Evaluable images were intraoperatively obtained for all patients. In two cases, the surgical procedure was changed on the basis of the images. Myelography did not provide any additional information. In the four years following the study, this intraoperative imaging technique has not been used again. Conclusion. Intraoperative imaging using the Iso-C3D system provides additional safety. It, however, has not become established as a routine procedure. PMID- 22091368 TI - Porcine and canine von Willebrand factor and von Willebrand disease: hemostasis, thrombosis, and atherosclerosis studies. AB - Use of animal models of inherited and induced von Willebrand factor (VWF) deficiency continues to advance the knowledge of VWF-related diseases: von Willebrand disease (VWD), thrombotic thrombocytopenic purpura (TTP), and coronary artery thrombosis. First, in humans, pigs, and dogs, VWF is essential for normal hemostasis; without VWF bleeding events are severe and can be fatal. Second, the ADAMTS13 cleavage site is preserved in all three species suggesting all use this mechanism for normal VWF multimer processing and that all are susceptible to TTP when ADAMTS13 function is reduced. Third, while the role of VWF in atherogenesis is debated, arterial thrombosis complicating atherosclerosis appears to be VWF dependent. The differences in the VWF gene and protein between humans, pigs, and dogs are relatively few but important to consider in the design of VWF-focused experiments. These homologies and differences are reviewed in detail and their implications for research projects are discussed. The current status of porcine and canine VWD are also reviewed as well as their potential role in future studies of VWF-related disorders of hemostasis and thrombosis. PMID- 22091371 TI - Percutaneous transfistulous interventions for intractable pancreatic fistula. AB - THREE TECHNIQUES FOR THE TREATMENT OF INTRACTABLE PANCREATIC FISTULA: percutaneous transfistulous pancreatic duct drainage (PTPD), percutaneous transfistulous pancreatojejunostomy (PTPJ), and percutaneous transfistulous pancreatic duct embolization (PTPE) are presented as treatment options for intractable pancreatic fistula. PTPD is effective for most cases of intractable fistula that communicate with the main pancreatic duct. However, PTPD itself is not enough in some specific cases. PTPJ and PTPE are applicable in such cases. PMID- 22091372 TI - Correlation between Rotator Cuff Tears and Systemic Atherosclerotic Disease. AB - The purpose of this study was to investigate the association of aortic arch calcification, a surrogate marker of atherosclerosis, with rotator cuff tendinosis and tears given the hypothesis that decreased tendon vascularity is a contributing factor in the etiology of tendon degeneration. A retrospective review was performed to identify patients ages 50 to 90 years who had a shoulder MRI and a chest radiograph performed within 6 months of each other. Chest radiographs and shoulder MRIs from 120 patients were reviewed by two sets of observers blinded to the others' conclusions. Rotator cuff disease was classified as tendinosis, partial thickness tear, and full thickness tear. The presence or absence of aortic arch calcification was graded and compared with the MRI appearance of the rotator cuff. The tendon tear grading was positively correlated with patient age. However, the tendon tear grading on MRI was not significantly correlated with the aorta calcification scores on chest radiographs. Furthermore, there was no significant correlation between aorta calcification severity and tendon tear grading. In conclusion, rotator cuff tears did not significantly correlate with aortic calcification severity. This suggests that tendon ischemia may not be associated with the degree of macrovascular disease. PMID- 22091373 TI - Technique of Peritoneal Catheter Placement under Fluroscopic Guidance. AB - Peritoneal catheters are mainly used for peritoneal dialysis in patients with end stage renal disease. Other uses of this catheter include intraperitoneal chemotherapy and gene therapy for ovarian cancer and draining of uncontrolled refractory ascites in patients with liver cirrhosis. Traditionally, surgeons place most of these peritoneal catheters either by laparoscopy or open laparotomy. We detail our percutaneous approach to placing peritoneal catheters using fluoroscopic guidance. We emphasize the use of additional ultrasound guidance, including gray scale and color Doppler ultrasound, to determine the safest puncture site and to guide the initial needle puncture in order to avoid bowel perforation and injury to epigastric artery. We present our experience in placing peritoneal catheters using this technique in 95 patients with various indications. Fluoroscopic guided percutaneous placement of peritoneal catheters is a safe, minimally invasive, and effective alternative to open surgical or laparoscopic placement. PMID- 22091375 TI - Current perspectives on percutaneous vertebroplasty: current evidence/controversies, patient selection and assessment, and technique and complications. AB - Osteoporotic-associated vertebral compression fractures are a major public health concern, dwarfing even hip fractures in incidence in the United States. These fractures carry a significant morbidity and mortality burden and also represent a major growing source of consumption of scarce heath resources. Percutaneous vertebroplasty remains a commonly used and safe technique for the symptomatic treatment of vertebral compression fractures, both osteoporotic- and neoplastic induced. By carefully selecting appropriate patients who are referred promptly, vertebroplasty can provide significant and durable pain relief over traditional conservative therapy. Recent controversies surrounding the evidence for vertebroplasty in osteoporotic-associated vertebral compression fractures are reviewed. A comprehensive step-by-step practical guide to performing vertebroplasty is then described. A brief description of patient selection, workup, as well as complications is also provided. PMID- 22091374 TI - Interventional radiology and the care of the oncology patient. AB - Interventional Radiology (IR) is occupying an increasingly prominent role in the care of patients with cancer, with involvement from initial diagnosis, right through to minimally invasive treatment of the malignancy and its complications. Adequate diagnostic samples can be obtained under image guidance by percutaneous biopsy and needle aspiration in an accurate and minimally invasive manner. IR techniques may be used to place central venous access devices with well established safety and efficacy. Therapeutic applications of IR in the oncology patient include local tumour treatments such as transarterial chemo-embolisation and radiofrequency ablation, as well as management of complications of malignancy such as pain, organ obstruction, and venous thrombosis. PMID- 22091376 TI - Thoracic radionecrosis following repeated cardiac catheterization. AB - Radiodermatitis is a known complication in patients having undergone radiotherapy. It usually appears 2 to 5 years after irradiation. We are reporting on a case of radiodermatitis that occurred within months after coronary dilatation and stenting. It started with painful swelling, followed by a typical appearance on the skin surface. Histological finding confirmed the diagnosis. However, magnetic resonance imaging showed changes in the subcutaneous tissue extending into the ribs. A radical debridement was performed including removal of a partially necrotic 4th rib. The defect was closed with a latissimus dorsi transposition flap. Our findings are compared with the literature reports. PMID- 22091377 TI - Malignant Cerebral Edema following CT Myelogram Using Isovue-M 300 Intrathecal Nonionic Water-Soluble Contrast: A Case Report. AB - Lumbar myelogram utilizing nonionic contrast is a commonly performed procedure to identify spinal pathology. Complication rates are low. Cerebral edema has been shown to occur following intrathecal injection of ionic contrast; however, no current literature has documented this complication relating to the ubiquitously used nonionic contrast medium. We report a case of a patient who developed malignant cerebral edema following a lumbar myelogram with Isovue-M 300 nonionic water-soluble intrathecal contrast. We believe this is the first reported case of cerebral edema resulting from the use of a nonionic contrast. PMID- 22091378 TI - Myelography in the Age of MRI: Why We Do It, and How We Do It. AB - Myelography is a nearly ninety-year-old method that has undergone a steady development from the introduction of water-soluble contrast agents to CT myelography. Since the introduction of magnetic resonance imaging into clinical routine in the mid-1980s, the role of myelography seemed to be constantly less important in spinal diagnostics, but it remains a method that is probably even superior to MRI for special clinical issues. This paper briefly summarizes the historical development of myelography, describes the technique, and discusses current indications like the detection of CSF leaks or cervical root avulsion. PMID- 22091379 TI - Esophageal inlet patch. AB - An inlet patch is a congenital anomaly consisting of ectopic gastric mucosa at or just distal to the upper esophageal sphincter. Most inlet patches are largely asymptomatic, but in problematic cases complications related to acid secretion such as esophagitis, ulcer, web and stricture may occur. The diagnosis of inlet patch is strongly suggested on barium swallow where the most common pattern consists of two small indentations on the wall of the esophagus. The diagnosis of inlet patch is confirmed via endoscopy with biopsy. At endoscopy, the lesion appears salmon-coloured and velvety and is easily distinguished from the normal grey-white squamous epithelium of the esophagus. The prominent margins correlate with the radiological findings of indentations and rim-like shadows on barium swallow. Histopathology provides the definitive diagnosis by demonstrating gastric mucosa adjacent to normal esophageal mucosa. No treatment is required for asymptomatic inlet patches. Symptomatic cases are treated with proton pump inhibitors to relieve symptoms related to acid secretion. Strictures and webs are treated with serial dilatation and should be biopsied to rule out malignancy. PMID- 22091380 TI - MR Angiography of Peripheral Arterial Stents: In Vitro Evaluation of 22 Different Stent Types. AB - Purpose. To evaluate stent lumen visibility of a large sample of different peripheral arterial (iliac, renal, carotid) stents using magnetic resonance angiography in vitro. Materials and Methods. 21 different stents and one stentgraft (10 nitinol, 7 316L, 2 tantalum, 1 cobalt superalloy, 1 PET + cobalt superalloy, and 1 platinum alloy) were examined in a vessel phantom (vessel diameters ranging from 5 to 13 mm) filled with a solution of Gd-DTPA. Stents were imaged at 1.5 Tesla using a T1-weighted 3D spoiled gradient-echo sequence. Image analysis was performed measuring three categories: Signal intensity in the stent lumen, lumen visibility of the stented lumen, and homogeneity of the stented lumen. The results were classified using a 3-point scale (good, intermediate, and poor results). Results. 7 stents showed good MR lumen visibility (4x nitinol, 2x tantalum, and 1x cobalt superalloy). 9 stents showed intermediate results (5x nitinol, 2x 316L, 1x PET + cobalt superalloy, and 1x platinum alloy) and 6 stents showed poor results (1x nitinol, and 5x 316L). Conclusion. Stent lumen visibility varies depending on the stent material and type. Some products show good lumen visibility which may allow the detection of stenoses inside the lumen, while other products cause artifacts which prevent reliable evaluation of the stent lumen with this technique. PMID- 22091381 TI - The risk of radiation exposure to the eyes of the interventional pain physician. AB - It is widely accepted that the use of medical imaging continues to grow across the globe as does the concern for radiation safety. The danger of lens opacities and cataract formation related to radiation exposure is well documented in the medical literature. However, there continues to be controversy regarding actual dose thresholds of radiation exposure and whether these thresholds are still relevant to cataract formation. Eye safety and the risk involved for the interventional pain physician is not entirely clear. Given the available literature on measured radiation exposure to the interventionist, and the controversy regarding dose thresholds, it is our current recommendation that the interventional pain physician use shielded eyewear. As the breadth of interventional procedures continues to grow, so does the radiation risk to the interventional pain physician. In this paper, we attempt to outline the risk of cataract formation in the scope of practice of an interventional pain physician and describe techniques that may help reduce them. PMID- 22091382 TI - MR Imaging of Prostate Cancer: Diffusion Weighted Imaging and (3D) Hydrogen 1 (H) MR Spectroscopy in Comparison with Histology. AB - Purpose. To evaluate retrospectively the impact of diffusion weighted imaging (DWI) and (3D) hydrogen 1 ((1)H) MR-spectroscopy (MRS) on the detection of prostatic cancer in comparison to histological examinations. MATERIALS AND METHODS: 50 patients with suspicion of prostate cancer underwent a MRI examination at a 1.5T scanner. The prostate was divided into sextants. Regions of interest were placed in each sextant to evaluate the apparent diffusion coefficient (ADC)-values. The results of the DWI as well as MRS were compared retrospectively with the findings of the histological examination. Sensitivity and specificity of ADC and metabolic ratio (MET)-both separately and in combination-for identification of tumor tissue was computed for variable discrimination thresholds to evaluate its receiver operator characteristic (ROC). An association between ADC, MET and Gleason score was tested by the non parametric Spearman rho-test. Results. The average ADC-value was 1.65 +/- 0.32mm(2)/s * 10(-3) in normal tissue and 0.96+/-0.24 mm(2)/s * 10(-3) in tumor tissue (mean +/- 1 SD). MET was 0.418 +/- 0.431 in normal tissue and 2.010 +/- 1.649 in tumor tissue. The area under the ROC curve was 0.966 (95%-confidence interval 0.941-0.991) and 0.943 (0.918-0.968) for DWI and MRS, respectively. There was a highly significant negative correlation between ADC-value and the Gleason score in the tumor-positive tissue probes (n = 62, rho = -0.405, P = .001). MRS did not show a significant correlation with the Gleason score (rho = 0.117, P = .366). By using both the DWI and MRS, the regression model provided sensitivity and specificity for detection of tumor of 91.9% and 98.3%, respectively. Conclusion. The results of our study showed that both DWI and MRS should be considered as an additional and complementary tool to the T2-weighted MRI for detecting prostate cancer. PMID- 22091383 TI - Differential effects of alpha-particle radiation and x-irradiation on genes associated with apoptosis. AB - This study examined differential effects of alpha-(alpha-) particle radiation and X-rays on apoptosis and associated changes in gene expression. Human monocytic cells were exposed to alpha-particle radiation and X-rays from 0 to 1.5 Gy. Four days postexposure, cell death was measured by flow cytometry and 84 genes related to apoptosis were analyzed using real-time PCR. On average, 33% of the cells were apoptotic at 1.5 Gy of alpha-particle radiation. Transcript profiling showed statistical expression of 15 genes at all three doses tested. Cells exposed to X rays were <5% apoptotic at ~1.5 Gy and induced less than a 2-fold expression in 6 apoptotic genes at the higher doses of radiation. Among these 6 genes, Fas and TNF-alpha were common to the alpha-irradiated cells. This data suggests that alpha-particle radiation initiates cell death by TNF-alpha and Fas activation and through intermediate signalling mediators that are distinct from X-irradiated cells. PMID- 22091384 TI - Advances in imaging for atrial fibrillation ablation. AB - Over the last fifteen years, our understanding of the pathophysiology of atrial fibrillation (AF) has paved the way for ablation to be utilized as an effective treatment option. With the aim of gaining more detailed anatomical representation, advances have been made using various imaging modalities, both before and during the ablation procedure, in planning and execution. Options have flourished from procedural fluoroscopy, electroanatomic mapping systems, preprocedural computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and combinations of these technologies. Exciting work is underway in an effort to allow the electrophysiologist to assess scar formation in real time. One advantage would be to lessen the learning curve for what are very complex procedures. The hope of these developments is to improve the likelihood of a successful ablation procedure and to allow more patients access to this treatment. PMID- 22091385 TI - Osteoid osteoma: can impedance levels in radiofrequency thermocoagulation predict recurrence? AB - Objective. To evaluate rise in impedance during percutaneous radiofrequency thermocoagulation (PRFTC) of osteoid osteomas as a predictor of local recurrence. Design and Patients. A prospective study of 23 patients (24 PRFTC procedures) with minimum of 2.25-year followup (average 3.3 years). Average age 19.6 years (range 4-44), sex ratio 15 : 8 (male : female), 16 nondiaphyseal, 7 diaphyseal. Results. In 19 procedures, an increase in impedance was measured-no recurrences have occurred in this group to date. In 5 procedures, no increase in impedance was seen (3 non-diaphyseal, 2 diaphyseal), and 1 recurrence has been seen in this group to date. This difference is statistically significant with a P value of .05. PMID- 22091386 TI - Clinical outcome of intra-arterial embolization for treatment of patients with pelvic trauma. AB - Purpose. To analyse the technical success of pelvic embolization in our institution and to assess periprocedural hemodynamic status and morbidity/mortality of all pelvic trauma patients who underwent pelvic embolization. Methods. A retrospective analysis of patients with a pelvic fracture due to trauma who underwent arterial embolization was performed. Clinical data, pelvic radiographs, contrast-enhanced CT-scans, and angiographic findings were reviewed. Subsequently, the technical success and peri-procedural hemodynamic status were evaluated and described. Results. 19 trauma patients with fractures of the pelvis underwent arterial embolization. Initially, 10/19 patients (53%) were hemodynamically unstable prior to embolization. Technical success of embolization was 100%. 14/19 patients (74%) were stable after embolization, and treatment success was high as 74%. Conclusion. Angiography with subsequent embolization should be performed in patients with a pelvic fracture due to trauma and hemodynamic instability, after surgical intervention or with a persistent arterial blush indicative of an active bleeding on CT. PMID- 22091388 TI - Signatures of drug sensitivity in nonsmall cell lung cancer. AB - We profiled receptor tyrosine kinase pathway activation and key gene mutations in eight human lung tumor cell lines and 50 human lung tumor tissue samples to define molecular pathways. A panel of eight kinase inhibitors was used to determine whether blocking pathway activation affected the tumor cell growth. The HER1 pathway in HER1 mutant cell lines HCC827 and H1975 were found to be highly activated and sensitive to HER1 inhibition. H1993 is a c-MET amplified cell line showing c-MET and HER1 pathway activation and responsiveness to c-MET inhibitor treatment. IGF-1R pathway activated H358 and A549 cells are sensitive to IGF-1R inhibition. The downstream PI3K inhibitor, BEZ-235, effectively inhibited tumor cell growth in most of the cell lines tested, except the H1993 and H1650 cells, while the MEK inhibitor PD-325901 was effective in blocking the growth of KRAS mutated cell line H1734 but not H358, A549 and H460. Hierarchical clustering of primary tumor samples with the corresponding tumor cell lines based on their pathway signatures revealed similar profiles for HER1, c-MET and IGF-1R pathway activation and predict potential treatment options for the primary tumors based on the tumor cell lines response to the panel of kinase inhibitors. PMID- 22091387 TI - Urine glycoprotein profile reveals novel markers for chronic kidney disease. AB - Chronic kidney disease (CKD) is a significant public health problem, and progression to end-stage renal disease leads to dramatic increases in morbidity and mortality. The mechanisms underlying progression of disease are poorly defined, and current noninvasive markers incompletely correlate with disease progression. Therefore, there is a great need for discovering novel markers for CKD. We utilized a glycoproteomic profiling approach to test the hypothesis that the urinary glycoproteome profile from subjects with CKD would be distinct from healthy controls. N-linked glycoproteins were isolated and enriched from the urine of healthy controls and subjects with CKD. This strategy identified several differentially expressed proteins in CKD, including a diverse array of proteins with endopeptidase inhibitor activity, protein binding functions, and acute phase/immune-stress response activity supporting the proposal that inflammation may play a central role in CKD. Additionally, several of these proteins have been previously linked to kidney disease implicating a mechanistic role in disease pathogenesis. Collectively, our observations suggest that the human urinary glycoproteome may serve as a discovery source for novel mechanism-based biomarkers of CKD. PMID- 22091389 TI - The application of a three-step proteome analysis for identification of new biomarkers of pancreatic cancer. AB - We searched for novel tumor markers of pancreatic cancer by three-step serum proteome analysis. Twelve serum abundant proteins were depleted using immunoaffinity columns followed by fractionation by reverse-phase high performance liquid chromatography. Proteins in each fraction were separated by two-dimensional gel electrophoresis. Then the gel was stained by Coomassie Brilliant Blue. Protein spots in which the expression levels were significantly different between cancer and normal control were identified by LC-MS/MS. One hundred and two spots were upregulated, and 84 spots were downregulated in serum samples obtained from patients with pancreatic cancers, and 58 proteins were identified by mass spectrometry. These candidate proteins were validated using western blot analysis and enzyme-linked immunosorbent assay (ELISA). As a result of these validation process, we could confirm that the serum levels of apolipoprotein A-IV, vitamin D-binding protein, plasma retinol-binding protein 4, and tetranectin were significantly decreased in patients with pancreatic cancer. PMID- 22091390 TI - Proteomic Approach to Evaluate Mechanisms That Contribute to Food Allergenicity: Comparative 2D-DIGE Analysis of Radioallergosorbent Test Positive and Negative Patients. AB - Proteomic profiles of RAST(+) subjects with severe food allergies and RAST(-) subjects were compared using 2D-DIGE analysis to obtain candidate biomarkers specific to food allergies. Our analysis highlighted 52 proteins that were differentially expressed between the RAST(+) and RAST(-) groups of which 37 were successfully identified that include chondroitin sulfates, zinc finger proteins, C-type lectins, retinoic acid binding proteins, heat shock proteins, myosin, cytokines, mast cell expressed proteins, and MAP kinases. Biological network analysis tool Metacore revealed that most of these regulated proteins play a role in immune tolerance, hypersensitivity and modulate cytokine patterns inducing a Th2 response that typically results in IgE-mediated allergic response which has a direct or indirect biological link to food allergy. Identifying unique biomarkers associated with certain allergic phenotypes and potentially cross-reactive proteins through bioinformatics analyses will provide enormous insight into the mechanisms that underlie allergic response in patients with food allergies. PMID- 22091391 TI - A bayesian model averaging approach to the quantification of overlapping peptides in an maldi-tof mass spectrum. AB - In a high-resolution MALDI-TOF mass spectrum, a peptide produces multiple peaks, corresponding to the isotopic variants of the molecules. An overlap occurs when two peptides appear in the vicinity of the mass coordinate, resulting in the difficulty of quantifying the relative abundance and the exact masses of these peptides. To address the problem, two factors need to be considered: (1) the variability pertaining to the abundances of the isotopic variants (2) extra information content needed to supplement the information contained in data. We propose a Bayesian model for the incorporation of prior information. Such information exists, for example, for the distribution of the masses of peptides and the abundances of the isotopic variants. The model we develop allows for the correct estimation of the parameters of interest. The validity of the modeling approach is verified by a real-life case study from a controlled mass spectrometry experiment and by a simulation study. PMID- 22091392 TI - Allelic Diversity of Major Histocompatibility Complex Class II DRB Gene in Indian Cattle and Buffalo. AB - The present study was conducted to study the diversity of MHC-DRB3 alleles in Indian cattle and buffalo breeds. Previously reported BoLA-DRB exon 2 alleles of Indian Zebu cattle, Bos taurus cattle, buffalo, sheep, and goats were analyzed for the identities and divergence among various allele sequences. Comparison of predicted amino acid residues of DRB3 exon 2 alleles with similar alleles from other ruminants revealed considerable congruence in amino acid substitution pattern. These alleles showed a high degree of nucleotide and amino acid polymorphism at positions forming peptide-binding regions. A higher rate of nonsynonymous substitution was detected at the peptide-binding regions, indicating that BoLA-DRB3 allelic sequence evolution was driven by positive selection. PMID- 22091393 TI - Glycolysis in the african trypanosome: targeting enzymes and their subcellular compartments for therapeutic development. AB - Subspecies of the African trypanosome, Trypanosoma brucei, which cause human African trypanosomiasis, are transmitted by the tsetse fly, with transmission essential lifecycle stages occurring in both the insect vector and human host. During infection of the human host, the parasite is limited to using glycolysis of host sugar for ATP production. This dependence on glucose breakdown presents a series of targets for potential therapeutic development, many of which have been explored and validated as therapeutic targets experimentally. These include enzymes directly involved in glucose metabolism (e.g., the trypanosome hexokinases), as well as cellular components required for development and maintenance of the essential subcellular compartments that house the major part of the pathway, the glycosomes. PMID- 22091394 TI - Glucose-6-phosphate dehydrogenase of trypanosomatids: characterization, target validation, and drug discovery. AB - In trypanosomatids, glucose-6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentosephosphate pathway, is essential for the defense of the parasite against oxidative stress. Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana G6PDHs have been characterized. The parasites' G6PDHs contain a unique 37 amino acid long N-terminal extension that in T. cruzi seems to regulate the enzyme activity in a redox-state-dependent manner. T. brucei and T. cruzi G6PDHs, but not their Leishmania spp. counterpart, are inhibited, in an uncompetitive way, by steroids such as dehydroepiandrosterone and derivatives. The Trypanosoma enzymes are more susceptible to inhibition by these compounds than the human G6PDH. The steroids also effectively kill cultured trypanosomes but not Leishmania and are presently considered as promising leads for the development of new parasite-selective chemotherapeutic agents. PMID- 22091395 TI - Protein methylation and stress granules: posttranslational remodeler or innocent bystander? AB - Stress granules contain a large number of post-translationally modified proteins, and studies have shown that these modifications serve as recruitment tags for specific proteins and even control the assembly and disassembly of the granules themselves. Work originating from our laboratory has focused on the role protein methylation plays in stress granule composition and function. We have demonstrated that both asymmetrically and symmetrically dimethylated proteins are core constituents of stress granules, and we have endeavored to understand when and how this occurs. Here we seek to integrate this data into a framework consisting of the currently known post-translational modifications affecting stress granules to produce a model of stress granule dynamics that, in turn, may serve as a benchmark for understanding and predicting how post-translational modifications regulate other granule types. PMID- 22091397 TI - Target Identification and Intervention Strategies against Kinetoplastid Protozoan Parasites. PMID- 22091396 TI - The Role of Protein Arginine Methylation in mRNP Dynamics. AB - In eukaryotes, messenger RNA biogenesis depends on the ordered and precise assembly of a nuclear messenger ribonucleoprotein particle (mRNP) during transcription. This process requires a well-orchestrated and dynamic sequence of molecular recognition events by specific RNA-binding proteins. Arginine methylation is a posttranslational modification found in a plethora of RNA binding proteins responsible for mRNP biogenesis. These RNA-binding proteins include both heterogeneous nuclear ribonucleoproteins (hnRNPs) and serine/arginine-rich (SR) proteins. In this paper, I discuss the mechanisms of action by which arginine methylation modulates various facets of mRNP biogenesis, and how the collective consequences of this modification impart the specificity required to generate a mature, translational- and export-competent mRNP. PMID- 22091398 TI - Cryptolepine-Induced Cell Death of Leishmania donovani Promastigotes Is Augmented by Inhibition of Autophagy. AB - Leishmania donovani are the causative agents of visceral leishmaniasis worldwide. Lack of vaccines and emergence of drug resistance warrants the need for improved drug therapy and newer therapeutic intervention strategies against leishmaniasis. In the present study, we have investigated the effect of the natural indoloquinoline alkaloid cryptolepine on L. donovani AG83 promastigotes. Our results show that cryptolepine induces cellular dysfunction in L. donovani promastigotes, which leads to the death of this unicellular parasite. Interestingly, our study suggest that cryptolepine-induced cell death of L. donovani is counteracted by initial autophagic features elicited by the cells. For the first time, we show that autophagy serves as a survival mechanism in response to cryptolepine treatment in L. donovani promastigotes and inhibition of autophagy causes an early increase in the amount of cell death. This study can be exploited for designing better drugs and better therapeutic strategies against leishmaniasis in future. PMID- 22091399 TI - Bioinformatic Analysis of Leishmania donovani Long-Chain Fatty Acid-CoA Ligase as a Novel Drug Target. AB - Fatty acyl-CoA synthetase (fatty acid: CoA ligase, AMP-forming; (EC 6.2.1.3)) catalyzes the formation of fatty acyl-CoA by a two-step process that proceeds through the hydrolysis of pyrophosphate. Fatty acyl-CoA represents bioactive compounds that are involved in protein transport, enzyme activation, protein acylation, cell signaling, and transcriptional control in addition to serving as substrates for beta oxidation and phospholipid biosynthesis. Fatty acyl-CoA synthetase occupies a pivotal role in cellular homeostasis, particularly in lipid metabolism. Our interest in fatty acyl-CoA synthetase stems from the identification of this enzyme, long-chain fatty acyl-CoA ligase (LCFA) by microarray analysis. We found this enzyme to be differentially expressed by Leishmania donovani amastigotes resistant to antimonial treatment. In the present study, we confirm the presence of long-chain fatty acyl-CoA ligase gene in the genome of clinical isolates of Leishmania donovani collected from the disease endemic area in India. We predict a molecular model for this enzyme for in silico docking studies using chemical library available in our institute. On the basis of the data presented in this work, we propose that long-chain fatty acyl-CoA ligase enzyme serves as an important protein and a potential target candidate for development of selective inhibitors against leishmaniasis. PMID- 22091400 TI - Experimental Chemotherapy for Chagas Disease: A Morphological, Biochemical, and Proteomic Overview of Potential Trypanosoma cruzi Targets of Amidines Derivatives and Naphthoquinones. AB - Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately eight million individuals in Latin America and is emerging in nonendemic areas due to the globalisation of immigration and nonvectorial transmission routes. Although CD represents an important public health problem, resulting in high morbidity and considerable mortality rates, few investments have been allocated towards developing novel anti-T. cruzi agents. The available therapy for CD is based on two nitro derivatives (benznidazole (Bz) and nifurtimox (Nf)) developed more than four decades ago. Both are far from ideal due to substantial secondary side effects, limited efficacy against different parasite isolates, long-term therapy, and their well-known poor activity in the late chronic phase. These drawbacks justify the urgent need to identify better drugs to treat chagasic patients. Although several classes of natural and synthetic compounds have been reported to act in vitro and in vivo on T. cruzi, since the introduction of Bz and Nf, only a few drugs, such as allopurinol and a few sterol inhibitors, have moved to clinical trials. This reflects, at least in part, the absence of well-established universal protocols to screen and compare drug activity. In addition, a large number of in vitro studies have been conducted using only epimastigotes and trypomastigotes instead of evaluating compounds' activities against intracellular amastigotes, which are the reproductive forms in the vertebrate host and are thus an important determinant in the selection and identification of effective compounds for further in vivo analysis. In addition, due to pharmacokinetics and absorption, distribution, metabolism, and excretion characteristics, several compounds that were promising in vitro have not been as effective as Nf or Bz in animal models of T. cruzi infection. In the last two decades, our team has collaborated with different medicinal chemistry groups to develop preclinical studies for CD and investigate the in vitro and in vivo efficacy, toxicity, selectivity, and parasite targets of different classes of natural and synthetic compounds. Some of these results will be briefly presented, focusing primarily on diamidines and related compounds and naphthoquinone derivatives that showed the most promising efficacy against T. cruzi. PMID- 22091401 TI - Evasion of Host Defence by Leishmania donovani: Subversion of Signaling Pathways. AB - Protozoan parasites of the genus Leishmania are responsible for causing a variety of human diseases known as leishmaniasis, which range from self-healing skin lesions to severe infection of visceral organs that are often fatal if left untreated. Leishmania donovani (L. donovani), the causative agent of visceral leishmaniasis, exemplifys a devious organism that has developed the ability to invade and replicate within host macrophage. In fact, the parasite has evolved strategies to interfere with a broad range of signaling processes in macrophage that includes Protein Kinase C, the JAK2/STAT1 cascade, and the MAP Kinase pathway. This paper focuses on how L. donovani modulates these signaling pathways that favour its survival and persistence in host cells. PMID- 22091402 TI - Screening the MayBridge Rule of 3 Fragment Library for Compounds That Interact with the Trypanosoma brucei myo-Inositol-3-Phosphate Synthase and/or Show Trypanocidal Activity. AB - Inositol-3-phosphate synthase (INO1) has previously been genetically validated as a drug target against Trypanosoma brucei, the causative agent of African sleeping sickness. Chemical intervention of this essential enzyme could lead to new therapeutic agents. Unfortunately, no potent inhibitors of INO1 from any organism have been reported, so a screen for potential novel inhibitors of T. brucei INO1was undertaken. Detection of inhibition of T. brucei INO1 is problematic due to the nature of the reaction. Direct detection requires differentiation between glucose-6-phosphate and inositol-3-phosphate. Coupled enzyme assays could give false positives as potentially they could inhibit the coupling enzyme. Thus, an alternative approach of differential scanning fluorimetry to identify compounds that interact with T. brucei INO1 was employed to screen ~670 compounds from the MayBridge Rule of 3 Fragment Library. This approach identified 38 compounds, which significantly altered the T(m) of TbINO1. Four compounds showed trypanocidal activity with ED50s in the tens of micromolar range, with 2 having a selectivity index in excess of 250. The trypanocidal and general cytotoxicity activities of all of the compounds in the library are also reported, with the best having ED50S of ~20 MUM against T. brucei. PMID- 22091403 TI - Identification and characterization of genes involved in leishmania pathogenesis: the potential for drug target selection. AB - Identifying and characterizing Leishmania donovani genes and the proteins they encode for their role in pathogenesis can reveal the value of this approach for finding new drug targets. Effective drug targets are likely to be proteins differentially expressed or required in the amastigote life cycle stage found in the patient. Several examples and their potential for chemotherapeutic disruption are presented. A pathway nearly ubiquitous in living cells targeted by anticancer drugs, the ubiquitin system, is examined. New findings in ubiquitin and ubiquitin like modifiers in Leishmania show how disruption of those pathways could point to additional drug targets. The programmed cell death pathway, now recognized among protozoan parasites, is reviewed for some of its components and evidence that suggests they could be targeted for antiparasitic drug therapy. Finally, the endoplasmic reticulum quality control system is involved in secretion of many virulence factors. How disruptions in this pathway reduce virulence as evidence for potential drug targets is presented. PMID- 22091404 TI - MiR-146a in Immunity and Disease. AB - MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of the innate as well as adaptive immunity. Given its importance in regulating key cellular functions, it is not surprising that miR-146a expression was also found dysregulated in different types of tumors. In this paper, we summarize recent progress in understanding the role of miR-146a in innate and adaptive immune responses, as well as in disease. PMID- 22091405 TI - Databases and bioinformatics tools for the study of DNA repair. AB - DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER) and nucleotide excision repair (NER) or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS). There are also other mechanisms of DNA repair such as homologous recombination repair (HRR), nonhomologous end-joining repair (NHEJ), or DNA damage response system (DDR). This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions. PMID- 22091406 TI - A perspective on the emergence of sialic acids as potent determinants affecting leishmania biology. AB - Leishmaniasis caused by Leishmania sp. has a wide range of manifestations from cutaneous to the deadly visceral form. They shuttle between the invertebrate and vertebrate hosts as promastigotes and amastigotes having adaptations for subverting host immune responses. Parasite-specific glycoconjugates have served as important determinants influencing parasite recognition, internalization, differentiation, multiplication, and virulence. Despite the steady progress in the field of parasite glycobiology, sialobiology has been a less traversed domain of research in leishmaniasis. The present paper focuses on identification, characterization, and differential distribution of sialoglycotope having the linkage-specific 9-O-acetylated sialic acid in promastigotes of different Leishmania sp. causing different clinical ramifications emphasizing possible role of these sialoglycotopes in infectivity, virulence, nitric oxide resistance, and host modulation in Leishmania spp. asserting them to be important molecules influencing parasite biology. PMID- 22091407 TI - Nucleotide Excision Repair in Caenorhabditis elegans. AB - Nucleotide excision repair (NER) plays an essential role in many organisms across life domains to preserve and faithfully transmit DNA to the next generation. In humans, NER is essential to prevent DNA damage-induced mutation accumulation and cell death leading to cancer and aging. NER is a versatile DNA repair pathway that repairs many types of DNA damage which distort the DNA helix, such as those induced by solar UV light. A detailed molecular model of the NER pathway has emerged from in vitro and live cell experiments, particularly using model systems such as bacteria, yeast, and mammalian cell cultures. In recent years, the versatility of the nematode C. elegans to study DNA damage response (DDR) mechanisms including NER has become increasingly clear. In particular, C. elegans seems to be a convenient tool to study NER during the UV response in vivo, to analyze this process in the context of a developing and multicellular organism, and to perform genetic screening. Here, we will discuss current knowledge gained from the use of C. elegans to study NER and the response to UV-induced DNA damage. PMID- 22091409 TI - Copper and its complexes in medicine: a biochemical approach. AB - The fundamental role of copper and the recognition of its complexes as important bioactive compounds in vitro and in vivo aroused an ever-increasing interest in these agents as potential drugs for therapeutic intervention in various diseases. The vast array of information available for their bioinorganic properties and mode of action in several biological systems, combined with the new opportunities offered by the flourishing technologies of medicinal chemistry, is creating an exciting scenario for the development of a novel generation of highly active drugs with minimized side effects which could add significantly to the current clinical research and practice. In this paper we attempt to summarize all the available-to-date information on these issues. PMID- 22091410 TI - Structure and Function of the Small MutS-Related Domain. AB - MutS family proteins are widely distributed in almost all organisms from bacteria to human and play central roles in various DNA transactions such as DNA mismatch repair and recombinational events. The small MutS-related (Smr) domain was originally found in the C-terminal domain of an antirecombination protein, MutS2, a member of the MutS family. MutS2 is thought to suppress homologous recombination by endonucleolytic resolution of early intermediates in the process. The endonuclease activity of MutS2 is derived from the Smr domain. Interestingly, sequences homologous to the Smr domain are abundant in a variety of proteins other than MutS2 and can be classified into 3 subfamilies. Recently, the tertiary structures and endonuclease activities of all 3 Smr subfamilies were reported. In this paper, we review the biochemical characteristics and structures of the Smr domains as well as cellular functions of the Smr-containing proteins. PMID- 22091408 TI - Use of antimony in the treatment of leishmaniasis: current status and future directions. AB - In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V) in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistant Leishmania donovani isolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala azar. PMID- 22091411 TI - Arsenic biotransformation as a cancer promoting factor by inducing DNA damage and disruption of repair mechanisms. AB - Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here. PMID- 22091412 TI - Role of cAMP Signaling in the Survival and Infectivity of the Protozoan Parasite, Leishmania donovani. AB - Leishmania donovani, while invading macrophages, encounters striking shift in temperature and pH (from 22 degrees C and pH 7.2 to 37 degrees C and pH 5.5), which act as the key environmental trigger for differentiation, and increases cAMP level and cAMP-mediated responses. For comprehensive understanding of cAMP signaling, we studied the enzymes related to cAMP metabolism. A stage-specific and developmentally regulated isoform of receptor adenylate cyclase (LdRACA) showed to regulate differentiation-coupled induction of cAMP. The soluble acidocalcisomal pyrophosphatase, Ldvsp1, was the major isoform regulating cAMP level in association with LdRACA. A differentially expressed soluble cytosolic cAMP phosphodiesterase (LdPDEA) might be related to infection establishment by shifting trypanothione pool utilization bias toward antioxidant defense. We identified and cloned a functional cAMP-binding effector molecule from L. donovani (a regulatory subunit of cAMP-dependent protein kinase, LdPKAR) that may modulate metacyclogenesis through induction of autophagy. This study reveals the significance of cAMP signaling in parasite survival and infectivity. PMID- 22091413 TI - The Role of miRNAs as Key Regulators in the Neoplastic Microenvironment. AB - The neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Although a large body of evidence has established the importance of the cancer microenvironment, the manners of crosstalk between it and the cancer cells still remains unclear. Emerging mechanisms of communication include microRNAs (miRNAs). miRNAs are small noncoding RNA molecules that are involved in the posttranscriptional regulation of mRNA. Both intracellular and circulating miRNAs are differentially expressed in cancer and some of these alterations have been correlated with clinical patient outcomes. The role of miRNAs in the tumor microenvironment has only recently become a focus of research, however. In this paper, we discuss the influence of miRNAs on the tumor microenvironment as it relates to cancer progression. We conclude that miRNAs are a critical component in understanding invasion and metastasis of cancer cells. PMID- 22091414 TI - Peptide Inhibition of Topoisomerase IB from Plasmodium falciparum. AB - Control of diseases inflicted by protozoan parasites such as Leishmania, Trypanosoma, and Plasmodium, which pose a serious threat to human health worldwide, depends on a rather small number of antiparasite drugs, of which many are toxic and/or inefficient. Moreover, the increasing occurrence of drug resistant parasites emphasizes the need for new and effective antiprotozoan drugs. In the current study, we describe a synthetic peptide, WRWYCRCK, with inhibitory effect on the essential enzyme topoisomerase I from the malaria causing parasite Plasmodium falciparum. The peptide inhibits specifically the transition from noncovalent to covalent DNA binding of P. falciparum topoisomerase I, while it does not affect the ligation step of catalysis. A mechanistic explanation for this inhibition is provided by molecular docking analyses. Taken together the presented results suggest that synthetic peptides may represent a new class of potential antiprotozoan drugs. PMID- 22091415 TI - Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis. AB - Amiodarone (AMIO), the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic Chagas' disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, Trypanosoma cruzi and Leishmania. In this work, we characterized the effects of AMIO on proliferation, mitochondrial physiology, and ultrastructure of Leishmania amazonensis promastigotes and intracellular amastigotes. The IC(50) values were 4.21 and 0.46 MUM against promastigotes and intracellular amastigotes, respectively, indicating high selectivity for the clinically relevant stage. We also found that treatment with AMIO leads to a collapse of the mitochondrial membrane potential (DeltaPsim) and to an increase in the production of reactive oxygen species, in a dose-dependent manner. Fluorescence microscopy of cells labeled with JC-1, a marker for mitochondrial energization, and transmission electron microscopy confirmed severe alterations of the mitochondrion, including intense swelling and modification of its membranes. Other ultrastructural alterations included (1) presence of numerous lipid-storage bodies, (2) presence of large autophagosomes containing part of the cytoplasm and membrane profiles, sometimes in close association with the mitochondrion and endoplasmic reticulum, and (3) alterations in the chromatin condensation and plasma membrane integrity. Taken together, our results indicate that AMIO is a potent inhibitor of L. amazonensis growth, acting through irreversible alterations in the mitochondrial structure and function, which lead to cell death by necrosis, apoptosis and/or autophagy. PMID- 22091416 TI - Cardiac tumors. AB - Cardiac tumors represent a relatively rare, yet challenging diagnosis. Secondary tumors are far more frequent than primary tumors of the heart. The majority of primary cardiac tumors is benign in origin, with primary malignant tumors accounting for 25% of cases. Metastatic tumors usually arise from lung, breast, renal cancer, melanomas, and lymphomas. Clinical manifestations of cardiac tumors depend on the size and location of the mass and the infiltration of adjacent tissues rather than the type of the tumor itself. Echocardiography is the main diagnostic tool for the detection of a cardiac mass. Other imaging modalities (C MRI, C-CT, 3D Echo) may offer further diagnostic information and the establishment of the diagnosis is made with histological examination. Management depends on the type of the tumor and the symptomatology of the patient. PMID- 22091417 TI - Controversies in the management of papillary thyroid cancer revisited. AB - The debate on the appropriate treatment of patients with papillary thyroid cancer (PTC) has persisted for several decades. The main controversies focus on the extent of surgery, the timing of central neck dissection, and the indications for radioactive iodine ablation. These controversies continue, for the most part, due to the good prognosis of PTC patients and the questionable effect these treatment modalities have on patient survival. This paper addresses these three controversies and the role of molecular tumor markers in the appropriate treatment selection. PMID- 22091419 TI - Serum Natrium Determines Outcome of Treatment of Advanced GIST with Imatinib: A Retrospective Study of 80 Patients from a Single Institution. AB - Treatment with tyrosine kinase inhibitors (TKIs) has drastically improved overall survival (OS) of patients with advanced GIST. The aim of this study is to evaluate the results of treatment with different TKIs on advanced GIST and identify prognostic factors for OS. The medical records of all patients treated at the Department of Oncology, Aarhus University Hospital were retrospectively reviewed. Between 2001 and 2009, 80 patients with advanced GIST were treated with imatinib as first-line therapy. The median OS was 44 months (95% CI 31-56), and the 5-year OS was 40%. Since 2005, 32 patients were treated with sunitinib as 2nd line therapy. The median time to progression was 9 months (95% CI: 3-13 months), and the 3-year OS was 30%. The data illustrate that data from large multicenter studies are reproducible in a single sarcoma centre. This retrospective study pointed to low serum sodium at the start of imatinib as a possible prognostic factor affecting OS. PMID- 22091418 TI - Pathway profiling and rational trial design for studies in advanced stage cervical carcinoma: a review and a perspective. AB - Multiple genetic abnormalities will have occurred in advanced cervical cancer and multiple targeting is likely to be needed to control tumor growth. To date, dominant therapeutic targets under scrutiny for cervical cancer treatment have been EGFR pathway and angiogenesis inhibition as well as anti-HPV vaccines. The potentially most effective targets to be blocked may be downstream from the membrane receptor or at the level of the nucleus. Alterations of the pathways involved in DNA repair and in checkpoint activations, as well as the specific site of HPV genome integration, appear worth assessing. For genetic mutational analysis, complete exon sequencing may become the norm in the future but at this stage frequent mutations (that matter) can be verified by PCR analysis. A precise documentation of relevant alterations of a large spectrum of protein biomarkers can be carried out by reverse phase protein array (RPPA) or by multiplex analysis. Clinical decision-making on the drug(s) of choice as a function of the biological alteration will need input from bio-informatics platforms as well as novel statistical designs. Endpoints are yet to be defined such as the loss (or reappearance) of a predictive biomarker. Single or dual targeting needs to be explored first in relevant preclinical animal and in xenograft models prior to clinical deployment. PMID- 22091420 TI - Morbidity and mortality of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: national cancer institute, Mexico city, Mexico. AB - Peritoneal carcinomatosis (PC) is generally considered a lethal disease, with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a new approach for peritoneal surface disease. This study investigated the early experience with this combined modality treatment at a single institute. From January 2007 to March 2010, 24 patients were treated After aggressive CS, with HIPEC (cisplatin 25 mg/m(2)/L and mitomycin C 3.3 mg/m(2)/L was administered for 90-minutes at 40.5 degrees C). These data suggest that aggressive CRS with HIPEC for the treatment of PC may result in low mortality and acceptable morbidity. Rigorous patient selection, appropriate and prudent operative procedures were associated with encouraging results in our experience. PMID- 22091421 TI - A very unusual presentation of metastatic colon cancer. AB - This case highlights two very rare complications of metastatic colorectal carcinoma. It describes a 59 year old female with both cutaneous and endometrial metastases from colorectal carcinoma. While both of these presentations are very unusual, they highlight the need to be vigilant about the detection of metastatic complications during follow up. PMID- 22091422 TI - A new classification and clinical predictivity for some naevus variants. AB - Background. The incidence of cutaneous melanoma is rapidly increasing in Europe. Active research is directed toward the identification of naevi as a risk factor. Objective. The aim of our case-control study was to observe different numbers of moles and different mole typology associations in order to evaluate clinical predictivity and to establish a new classification for some naevus variants. Methods. A case-control study was carried out, enrolling 64 cases affected by melanoma and 183 controls, between October 2009 and February 2011. Each patient was interviewed and subjected to clinical examination. The resulting data were analysed using the statistical elaboration program SPSS 16.0. Results. The association of target naevus with other variants increases the degree of risk (target + small brown Odds Ratio 5.25; confidence interval 1.8-15.4); (target + small brown + small black + large brown odds ratio 5.0; confidence interval 1.1 22.4). Therefore, other variants and/or other variant combinations do not significantly increase risk. Conclusion. People presenting two naevus variants in association with other naevus variants seem to run a major risk. The general nonuniformity of the whole naevus panorama should be carefully considered. PMID- 22091423 TI - Predictors of nonsentinel nodal involvement to aid intraoperative decision making in breast cancer patients with positive sentinel lymph nodes. AB - Background. Up to 60% of patients with a positive sentinel lymph node (SLN) have no additional nodal involvement and do not benefit from completion axillary lymph node dissection (ALND). We aim to identify factors predicting for non-SLN involvement and to validate the MSKCC nomogram and Tenon score in our population. Methods. Retrospective review was performed of 110 consecutive patients with positive SLNs who underwent ALND over an 8-year period. Results. Fifty patients (45%) had non-SLN involvement. Non-SLN involvement correlated positively with the number of positive SLNs (P = 0.04), macrometastasis (P = 0.01), and inversely with the total number of SLNs harvested (P = 0.03). The MSKCC nomogram and Tenon score both failed to perform as previously reported. Conclusions. The MSKCC nomogram and Tenon score have limited value in our practice. Instead, we identified three independent predictors, which are more relevant in guiding the intraoperative decision for ALND. PMID- 22091425 TI - Spermatic cord metastasis of primary hepatocellular carcinoma presenting as an inguinal mass: a case report. AB - Most spermatic cord masses are benign, and malignant spermatic cord tumors are uncommon. Spermatic cord metastases originating from hepatocellular carcinoma (HCC) have not been previously reported in the English language literature as determined by a PubMed search. We report a male patient who presented with a painful palpable mass in the right inguinal area. The patient was diagnosed with HCC in 2004 and undertook a nonsurgical approach to control the cancer. A radical orchiectomy was performed, and the pathological report showed metastatic HCC in the spermatic cord. The patient received palliative radiation therapy because of a positive surgical margin. No recurrence was noted after 6 months of followup. PMID- 22091424 TI - Use of pattern recognition analysis to identify underlying relationships of Doxorubicin derivatives optimized for breast cancer treatment. AB - Introduction. Treatment of breast cancer includes surgery, drugs (hormone therapy and chemotherapy), and radiation. A discussion of eight drug constructs for the treatment of breast cancer, derived through application of in silico optimized molecular properties and substituent substitution, are analyzed using pattern recognition techniques. Methods and Materials. Determined properties of these eight compounds (inclusive of doxorubicin) showed a Log P varying from 0.567 to 4.137, rotatable bonds from 5 to 12, polar surface area from 195.1 A(2) to 206.1 A(2), and water solubility from 0.00873 mg/L to 390 mg/L. Analysis of similarity (ANOSIM), hierarchical cluster analysis, and neighbor-joining cluster analysis elucidated relationships among the drugs that are useful for pharmaceutical consideration. Results and Discussion. Although the new derivatives share the same parent scaffold (doxorubicin), elucidation by analysis of similarity (ANOSIM) indicates that these assorted compounds are substantially distinct. The number of oxygen and nitrogen atoms (hydrogen bond acceptors) remained constant at 12 for compounds. Although violations of the Rule of five remained constant at three for all compounds, the variation of Log P and water solubility offers potentially beneficial medicinal activity for this group of anticancer agents that may enhance the antitumor activity of these anthracycline antibiotics. Hierarchical cluster analysis results clearly differentiated the parent doxorubicin from all higher molecular weight analogs. This outcome is confirmed with the use of neighbor-joining cluster analysis. Conclusion. By utilizing in silico optimization with pattern recognition analysis, potentially advantageous analogs can be elucidated from known effective pharmaceuticals. PMID- 22091426 TI - Incidentally detected squamous cell carcinoma of renal pelvis in patients with staghorn calculi: case series with review of the literature. AB - Squamous cell carcinoma of the renal pelvis is a rare neoplasm, often unsuspected clinically due to its rarity and ambiguous clinical and radiological features, and hence patients present at advanced stages resulting in poor prognosis. We report here four cases of incidentally diagnosed primary renal squamous cell carcinoma, treated at our hospital over a short span of one year, and review the relevant literature. Mean age of the patients (3 males, 1 female) was 60 years. All suffered from staghorn stones. Interestingly, renal carcinoma was unsuspected clinically in all patients. In one case, a computerised tomography scan showed a suspicious nodule. All underwent nephrectomy for nonfunctioning kidney. In just two cases, tumor was identified on gross examination, while the other two only showed thickened pelvis. Our series emphasises the need for pelvicalyceal biopsy during treatment for long-standing nephrolithiasis, and thorough sampling of the renal pelvis in nephrectomy specimen of such patients. PMID- 22091427 TI - Prognostic Significance of the Number of Removed and Metastatic Lymph Nodes and Lymph Node Ratio in Breast Carcinoma Patients with 1-3 Axillary Lymph Node(s) Metastasis. AB - We evaluated the prognostic significance of lymph node ratio (LNR), number of metastatic lymph nodes divided by number of removed nodes in 924 breast carcinoma patients with 1-3 metastatic axillary lymph node(s). The most significant LNR threshold value separating patients in low- and high-risk groups with significant survival difference was 0.20 for disease-free survival (P < 0.001), 0.30 for locoregional recurrence-free survival (P < 0.001), and 0.15 for distant metastasis-free survival (P < 0.001), and the patients with lower LNR had better survival. All three LNR threshold values had independent prognostic significance in Cox analysis (P < 0.001 for all three of them). In conclusion, LNR is a useful tool in separating breast carcinoma patients with 1-3 metastatic lymph node(s) into low- and high-risk prognostic groups. PMID- 22091428 TI - Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer. AB - Background. To our knowledge, the hormone receptor status of noncontiguous ductal carcinoma in situ (DCIS) occurring concurrently in ER/PgR-negative invasive cancer has not been studied. The current study was undertaken to investigate the ER/PgR receptor status of DCIS of the breast in patients with ER/PgR-negative invasive breast cancer. Methods. We reviewed the immunohistochemical (IHC) staining for ER and PgR of 187 consecutive cases of ER/PgR-negative invasive breast cancers, collected from 1995 to 2002. To meet the criteria for the study, we evaluated ER/PgR expression of DCIS cancer outside of the invasive breast cancer. Results. A total of 37 cases of DCIS meeting the above criteria were identified. Of these, 16 cases (43.2%) showed positive staining for ER, PgR, or both. Conclusions. In our study of ER/PgR-negative invasive breast cancer we found that in 8% of cases noncontiguous ER/PR-positive DCIS was present. In light of this finding, it may be important for pathologists to evaluate the ER/PgR status of DCIS occurring in the presence of ER/PgR-negative invasive cancer, as this subgroup could be considered for chemoprevention. PMID- 22091429 TI - Multiple endocrine neoplasia 2a presenting with pheochromocytoma and pituitary macroadenoma. AB - Multiple Endocrine Neoplasia type 2A (MEN-2a) is a rare disease associated with tumors of endocrine organs. Presentation most commonly is with medullary thyroid cancer and infrequently with other complaints. Pituitary adenoma has been seen coincidentally with this disease very rarely. Presented is a case of coincident MEN-2a with a symptomatic pituitary adenoma and an asymptomatic pheochromocytoma. A brief review is also provided. PMID- 22091430 TI - Association of epidermal growth factor receptor mutations with metastatic presentations in non-small cell lung cancer. AB - We performed this retrospective study to assess the association of epidermal growth factor receptor (EGFR) with metastatic presentations in advanced non-small cell lung cancer (NSCLC). The data from 125 patients with stage III or IV NSCLC were analyzed. We detected EGFR mutations in 36 NSCLC patients. EGFR mutations were predominant in never-smokers (P < .001), patients with adenocarcinomas (P < .001), and female patients (P < .001). When the metastatic sites were analyzed, pleural metastases were associated with a high incidence of EGFR mutations (P = .028). Particularly, pleural metastases with minimal effusion (PMME) were associated with EGFR mutational status (P = .001). Patients with N3 lesions were less likely to harbor EGFR mutations (P = .033). On multivariate analysis, N3 lesions (P = .017) and PMME (P < .001) remained significant factors for EGFR mutations. EGFR mutations may be associated with different presentations of pleural and N3 nodal metastases. PMID- 22091431 TI - Ten-year survival after liver resection for colorectal metastases: systematic review and meta-analysis. AB - Background. Liver resection in metastatic colorectal cancer is proved to result in five-year survival of 25-40%. Several factors have been investigated to look for prognostic factors stratifications such as resection margins, node involvement in the primary disease, and interval between the primary disease and liver metastases. Methods. We searched MEDLINE and EMBASE for studies that reported ten-year survival. Metaanalysis was performed to analyse the effect of recognised prognostic factors on cure rate for colorectal metastases. The meta analysis was performed according to Ottawa-Newcastle method of analysis for nonrandomised trials and according to the guidelines of the PRISMA. Results. Eleven studies were included in the analysis, which showed a ten-year survival rate of 12-36%. Factors that have favourable impact are clear resection margin, low level of CEA, single metastatic deposit, and node negative disease. The only factor that excluded patients from cure is the positive status of the resection margin. Conclusion. Predicted ten-year survival after liver resection for colorectal metastases varies from 12 to 36%. Only positive resection margins resulted in no 10-year survivors. No patient can be excluded from consideration for liver resection so long the result is negative margins. PMID- 22091433 TI - Evaluating smoking cessation interventions and cessation rates in cancer patients: a systematic review and meta-analysis. AB - Background. Tobacco smoking cessation interventions in the oncology population are an important part of comprehensive treatment plan. Objectives. To evaluate through a systematic review smoking cessation interventions and cessation rates in cancer patients. Search Strategy. The literature was searched using Medline, EMBASE, and the Cochrane Library (inception to November 2010) by three independent review authors. Selection Criteria. Studies were included if tobacco smoking cessation interventions were evaluated and patients were randomized to usual care or an intervention. The primary outcome measure was cessation rates. Data Collection and Analysis. Two authors extracted data independently for each paper, with disagreements resolved by consensus. Main Results. The systematic review found eight RCTs investigating smoking cessation interventions in the oncology patient population. Pooled relative risks were calculated from two groups of RCTs of smoking cessation interventions based on followup duration. In both groups, the pooled relative risk did not suggest a statistically significant improvement in tobacco cessation compared to usual care. Conclusions. Our review demonstrates that recent interventions in the last decade which are a combination of non-pharmacological and pharmacological approaches yield a statistically significant improvement in smoking cessation rates compared to usual care. PMID- 22091434 TI - Downregulation of the adenosine a2b receptor by RNA interference inhibits hepatocellular carcinoma cell growth. AB - To investigate the biological effect of adenosine A2b receptor (A2bR) on the human hepatocellular carcinoma cell line HepG2, three A2bR siRNA constructs were transiently transfected into HepG2 cells. The results showed that A2bR siRNA reduced the levels of A2bR mRNA and protein. In order to further detect the function of A2bR, we established a stable hepatocellular carcinoma cell line (HepG2) expressing siRNA targeting the adenosine A2b receptor. Targeted RNAi significantly inhibited tumor cell growth in vitro, and flow cytometry (FCM) showed that significantly more cells expressing A2bR siRNA were in the G0/G1 phase compared to the untransfected group ((89.56% +/- 3.15%) versus (56.19% +/- 1.58%), P < 0.01). These results indicated that silencing the expression of adenosine A2b receptor in HepG2 cells can suppress cell growth effectively by blocking the cell cycle. Downregulation of adenosine A2b receptor gene expression with RNA interference could be a new approach to hepatocellular carcinoma therapy. PMID- 22091435 TI - Prepubertal daidzein exposure enhances mammary gland differentiation and regulates the expression of estrogen receptor-alpha and apoptotic proteins. AB - Mechanism of chemoprevention by daidzein (500 MUg/g bwt) was examined by injecting it subcutaneously at 16th, 18th, and 20th day postpartum, followed by counting of terminal end buds (TEBs), terminal ducts (TDs), and lobules and immunohistochemistry of ER-alpha, Bcl2, Bax, and caspase-3. DNA fragmentation was also analysed to measure the apoptosis level. Estradiol benzoate (EB) (500 ng/g bwt) and dimethyl sulphoxide (DMSO) were used as reference and vehicle, respectively. Observations show a significant enhancement of mammary gland differentiation at postnatal day 21 (PND21) as well as PND50. There was a significant decrease of ER-alpha expression at PND21 and increase in its expression at PND50, in daidzein-treated animals. The ratio of expression of Bcl 2 to Bax proteins increased at PND50 the same whereas, it decreased at PND50 due to daidzein. An increased expression of caspase-3 and DNA fragmentation was also seen due to daidzein at PND50. The mammary gland of EB-treated animals showed response a somewhat similar to that of daidzein-treated animals. PMID- 22091432 TI - Innovative Therapies against Human Glioblastoma Multiforme. AB - Glioblastoma multiforme is the most invasive and aggressive brain tumor in humans, and despite the latest chemical and radiative therapeutic approaches, it is still scarcely sensitive to these treatments and is generally considered an incurable disease. This paper will focus on the latest approaches to the treatment of this cancer, including the new chemicals such as proautophagic drugs and kinases inhibitors, and differentiating agents. In this field, there have been opening new perspectives as the discovery of possible specific targets such as the EGFRvIII, a truncated form of the EGF receptor. Antibodies against these targets can be used as proapoptotic agents and as possible carriers for chemicals, drugs, radioisotopes, and toxins. In this paper, we review the possible mechanism of action of these therapies, with particular attention to the combined use of toxic substances (for example, immunotoxins) and antiproliferative/differentiating compounds (i.e., ATRA, PPARgamma agonists). All these aspects will be discussed in the view of progress clinical trials and of possible new approaches for directed drug formulations. PMID- 22091436 TI - Novel strategy with gemcitabine for advanced pancreatic cancer. AB - 5-fluorouracil (5-FU) is widely used in chemotherapy for gastric and colorectal cancer, but gemcitabine (GEM), and not 5-FU, is approved as a standard drug for use in pancreatic cancer. Interindividual variation in the enzyme activity of the GEM metabolic pathway can affect the extent of GEM metabolism and the efficacy of GEM chemotherapy. Human equilibrative nucleoside transporter 1 (hENT1) is recognized as a major transporter of GEM into cells. In addition, a factor that activates hENT1 is the inhibition of thymidylate synthase (TS), one of the 5-FU metabolic enzymes; TS inhibition mediates depleting intracellular nucleotide pools, resulting in the activation of the salvage pathway mediated through hENT1. In this paper, the role of 5-FU in GEM-based chemotherapy for pancreatic cancer is discussed with special emphasis on enzymes involved in the 5-FU and GEM metabolic pathways and in the correlation between GEM responsiveness and the expression of 5-FU and GEM metabolic enzymes. PMID- 22091437 TI - Screening for Prostate Cancer by Digital Rectal Examination and PSA Determination in Senegal. AB - Objectives. The goal of our study was to investigate the prevalence of prostate cancer in an unselected population of Senegalese men. Patients and Methods. We conducted the study over two years (2008 and 2009) on an unselected population of 572 Senegalese men, aged 35 and older. The following parameters have been investigated: the subject's age, the presence or absence of urination disorders, the family's history of prostate cancer or prostate surgery, the aspects of the prostate on digital rectal examination (DRE), the total PSA level, and the outcomes of the prostate biopsies. Data entry was performed with Epi Info 6 software and was analyzed and recorded using Excel software. We performed mean and frequency calculations. Results. The mean age of our patients was 65.5 years, with extremes of 38 and 93 years. Age groups from 50 to 59 and from 60 to 69 were the most represented. DRE was normal in the age group from 35 to 39, and only one patient in the age group from 40 to 49 had a prostate nodule. PSA level was greater than or equal to 4 ng/mL in 66 cases. A total of 5.4% patients had a PSA level greater than or equal to 10 ng/mL. Only two patients in the age group from 40 to 49 had a PSA level greater than 4 ng/mL. Of the 72 biopsies we performed, prostatic adenocarcinoma was found in 30.6% of the cases. It is the only type of prostate cancer we found in our series. The cases of prostate cancer were mostly observed in the age groups from 60 to 69 and from 70 to 79. No cases were detected for ages younger than 50. DRE gave indications of possible adenocarcinoma in 27.30% cases. Its sensitivity was 27%, while its positive predictive value was estimated at 35%. Of all positive biopsies, 4.5% had a PSA level between 0 and 3.9 ng/mL. In this case, the sensitivity of PSA was 95.5%, and the positive predictive value was 31.8%. High-grade intraepithelial neoplasiae were observed in 21 cases. Conclusion. Prostate cancer is frequent in Senegal, and screening remains the best way for early diagnosis. PMID- 22091438 TI - In colorectal liver metastases, the presence of extrahepatic disease correlates with the pathology of the primary tumour. AB - Background. FDG-PET scan detects extrahepatic metastases in 20% of patients with colorectal liver metastases but it is reported to have approximately 16% false negative rates. Patients and Methods. Patients who had PET scan for metastatic colorectal cancer at Westmead Hospital between March 2006 and March 2010 were reviewed retrospectively. The results of PET scan were correlated with tumour characteristics that were thought to affect the overall prognosis. Results. Degree of tumour differentiation and vascular invasion were significantly predictive for the presence of extrahepatic disease on PET scan, also did the level of CEA. Conclusion. The detection of extrahepatic disease in colorectal liver metastases correlates with the biologic behaviour of the primary tumour. Poorly differentiated tumours and those with lymphovascular invasion behave in aggressive fashion and likely to have wide-spread metastases. This should be considered when contemplating liver resection for colorectal metastases. PMID- 22091440 TI - Incidental Parathyroid Disease during Thyroid Surgery: Should We Remove Them? AB - Aim. Despite an incidence of parathyroid "incidentalomas" of 0.2%-4.5%, only approximately 135 cases have been reported in the literature. We present eight patients in whom an incidental abnormal parathyroid gland was found during routine thyroid surgery. We have reviewed the literature and postulate whether these glands could represent further evidence of a preclinical stage of primary hyperparathyroidism. Methods. A retrospective analysis of all 236 thyroid operations performed by a single surgeon was performed to identify patients in whom abnormal parathyroid tissue was removed at surgery. Results. 8/236 patients (3.39%) had a single macroscopically abnormal parathyroid gland removed and sent for analysis. Seven patients were found to have histological evidence of a parathyroid adenoma or hyperplasia. None of the patients had abnormal serum calcium detected preoperatively. Postoperatively, four patients had normal calcium, three had temporary hypocalcaemia and one refused followup. No patients had recurrent laryngeal nerve impairment. Conclusions. Despite the risk of removing a histologically normal gland, we believe that when parathyroid "incidentalomas" are found during surgery they should be excised and sent for histological analysis. We have found this to be a safe procedure with minimal morbidity to the patient. As the natural history of primary hyperparathyroidism is better understood, these glands found in normocalcaemic patients may in fact represent the early or preclinical phase of the disease. By removing them at the original operation, the patient is saved redo neck surgery with its high complication rate as or when clinically apparent primary hyperparthryoidism develops in the future. PMID- 22091439 TI - A systematic review of randomized controlled interventions for parents' distress in pediatric leukemia. AB - Objective. This review aims to summarize the existing evidence concerning interventions towards reducing stress in parents with a child with leukemia and their effect in child and family wellbeing. Methods. A systematic review strategy was conducted using MEDLINE covering the period January 1980 to June 2010. Results. Seven randomized controlled trials met the inclusion criteria including in total 1045 parents participants. A variety of cognitive-behavioral interventions problem-solving skills training programs have been used for managing distress in parents and children. Outcome measures are assessed by self report, observer report, behavioral/psychological, and physiological measures. The most prominent methodological problems were the marked heterogeneity in stress measurement and the relative absence of proper measurement and adjustment of moderating and mediating factors. The largest effect has been obtained by combined cognitive-behavioral interventions with promising but limited evidence for several other psychological interventions. Conclusions. Recommendations for future RCTs are provided, and particular attention to the quality of trial design and reporting is highlighted. PMID- 22091441 TI - Morphological analysis of optical coherence tomography images for automated classification of gastrointestinal tissues. AB - The impact of digestive diseases, which include disorders affecting the oropharynx and alimentary canal, ranges from the inconvenience of a transient diarrhoea to dreaded conditions such as pancreatic cancer, which are usually fatal. Currently, the major limitation for the diagnosis of such diseases is sampling error because, even in the cases of rigorous adherence to biopsy protocols, only a tiny fraction of the surface of the involved gastrointestinal tract is sampled. Optical coherence tomography (OCT), which is an interferometric imaging technique for the minimally invasive measurement of biological samples, could decrease sampling error, increase yield, and even eliminate the need for tissue sampling provided that an automated, quick and reproducible tissue classification system is developed. Segmentation and quantification of ophthalmologic pathologies using OCT traditionally rely on the extraction of thickness and size measures from the OCT images, but layers are often not observed in nonopthalmic OCT imaging. Distinct mathematical methods, namely Principal Component Analysis (PCA) and textural analyses including both spatial textural analysis derived from the two-dimensional discrete Fourier transform (DFT) and statistical texture analysis obtained independently from center symmetric autocorrelation (CSAC) and spatial grey-level dependency matrices (SGLDM), have been previously reported to overcome this problem. We propose an alternative approach consisting of a region segmentation according to the intensity variation along the vertical axis and a pure statistical technique for feature quantification, i.e. morphological analysis. Qualitative and quantitative comparisons with traditional approaches are accomplished in the discrimination of freshly-excised specimens of gastrointestinal tissues to exhibit the feasibility of the proposed method for computer-aided diagnosis (CAD) in the clinical setting. PMID- 22091442 TI - Enhanced video indirect ophthalmoscopy (VIO) via robust mosaicing. AB - Indirect ophthalmoscopy (IO) is the standard of care for evaluation of the neonatal retina. When recorded on video from a head-mounted camera, IO images have low quality and narrow Field of View (FOV). We present an image fusion methodology for converting a video IO recording into a single, high quality, wide FOV mosaic that seamlessly blends the best frames in the video. To this end, we have developed fast and robust algorithms for automatic evaluation of video quality, artifact detection and removal, vessel mapping, registration, and multi frame image fusion. Our experiments show the effectiveness of the proposed methods. PMID- 22091443 TI - Fast macro-scale transmission imaging of microvascular networks using KESM. AB - Accurate microvascular morphometric information has significant implications in several fields, including the quantification of angiogenesis in cancer research, understanding the immune response for neural prosthetics, and predicting the nature of blood flow as it relates to stroke. We report imaging of the whole mouse brain microvascular system at resolutions sufficient to perform accurate morphometry. Imaging was performed using Knife-Edge Scanning Microscopy (KESM) and is the first example of this technique that can be directly applied to clinical research. We are able to achieve ~ 0.7MUm resolution laterally with 1MUm depth resolution using serial sectioning. No alignment was necessary and contrast was sufficient to allow segmentation and measurement of vessels. PMID- 22091444 TI - Automated detection and cell density assessment of keratocytes in the human corneal stroma from ultrahigh resolution optical coherence tomograms. AB - Keratocytes are fibroblast-like cells that maintain the optical clarity and the overall health of the cornea. The ability to measure precisely their density and spatial distribution in the cornea is important for the understanding of corneal healing processes and the diagnostics of some corneal disorders. A novel computerized approach to detection and counting of keratocyte cells from ultra high resolution optical coherence tomography (UHR-OCT) images of the human corneal stroma is presented. The corneal OCT data is first processed using a state-of-the-art despeckling algorithm to reduce the effect of speckle on detection accuracy. A thresholding strategy is then employed to allow for improved delineation of keratocyte cells by suppressing similarly shaped features in the data, followed by a second-order moment analysis to identify potential cell nuclei candidates. Finally, a local extrema strategy is used to refine the candidates to determine the locations and the number of keratocyte cells. Cell density distribution analysis was carried in 3D UHR-OCT images of the human corneal stroma, acquired in-vivo. The cell density results obtained using the proposed novel approach correlate well with previous work on computerized keratocyte cell counting from confocal microscopy images of human cornea. PMID- 22091445 TI - Changes to lipid droplet configuration in mCMV-infected fibroblasts: live cell imaging with simultaneous CARS and two-photon fluorescence microscopy. AB - We have performed multimodal imaging of live fibroblast cells infected by murine cytomegalovirus (mCMV). The infection process was monitored by imaging the two photon fluorescence signal from a GFP-expressing strain of mCMV, whilst changes to lipid droplet configuration were observed by CARS imaging. This allowed us to identify three visually distinct stages of infection. Quantitative analysis of lipid droplet number and size distributions were obtained from live cells, which showed significant perturbations across the different stages of infection. The CARS and two-photon images were acquired simultaneously and the experimental design allowed incorporation of an environmental control chamber to maintain cell viability. Photodamage to the live cell population was also assessed. PMID- 22091446 TI - Increasing the field-of-view of dynamic cardiac OCT via post-acquisition mosaicing without affecting frame-rate or spatial resolution. AB - Optical coherence tomography (OCT) allows imaging dynamic structures and fluid flow within scattering tissue, such as the beating heart and blood flow in murine embryos. For any given system, the frame rate, spatial resolution, field-of-view (FOV), and signal-to-noise ratio (SNR) are interconnected: favoring one aspect limits at least one of the others due to optical, instrumentation, and software constraints. Here we describe a spatio-temporal mosaicing technique to reconstruct high-speed, high spatial-resolution, and large-field-of-view OCT sequences. The technique is applicable to imaging any cyclically moving structure and operates on multiple, spatially overlapping tiled image sequences (each sequence acquired sequentially at a given spatial location) and effectively decouples the (rigid) spatial alignment and (non-rigid) temporal registration problems. Using this approach we reconstructed full-frame OCT sequences of the beating embryonic rat heart (11.5 days post coitus) and compared it to direct imaging on the same system, demonstrating a six-fold improvement of the frame rate without compromising spatial resolution, FOV, or SNR. PMID- 22091447 TI - Split operator method for fluorescence diffuse optical tomography using anisotropic diffusion regularisation with prior anatomical information. AB - Fluorescence diffuse optical tomography (fDOT) is an imaging modality that provides images of the fluorochrome distribution within the object of study. The image reconstruction problem is ill-posed and highly underdetermined and, therefore, regularisation techniques need to be used. In this paper we use a nonlinear anisotropic diffusion regularisation term that incorporates anatomical prior information. We introduce a split operator method that reduces the nonlinear inverse problem to two simpler problems, allowing fast and efficient solution of the fDOT problem. We tested our method using simulated, phantom and ex-vivo mouse data, and found that it provides reconstructions with better spatial localisation and size of fluorochrome inclusions than using the standard Tikhonov penalty term. PMID- 22091448 TI - Evaluation of a spectrally resolved scattering microscope. AB - A scattering microscope was developed to investigate single cells and biological microstructures by light scattering measurements. The spectrally resolved part of the setup and its validation are shown in detail. The analysis of light scattered by homogenous polystyrene spheres allows the determination of their diameters using Mie theory. The diameters of 150 single polystyrene spheres were determined by the spectrally resolved scattering microscope. In comparison, the same polystyrene suspension stock was investigated by a collimated transmission setup. Mean diameters and standard deviations of the size distribution were evaluated by both methods with a statistical error of less than 1nm. The systematic errors of both devices are in agreement within the measurement accuracy. PMID- 22091449 TI - In vivo evaluation of demyelination and remyelination in a nerve crush injury model. AB - Nerves of the peripheral nervous system have, to some extent, the ability to regenerate after injury, particularly in instances of crush or contusion injuries. After a controlled crush injury of the rat sciatic nerve, demyelination and remyelination are followed with functional assessments and imaged both ex vivo and in vivo over the course of 4 weeks with video-rate coherent anti-Stokes Raman scattering (CARS) microscopy. A new procedure compatible with live animal imaging is developed for performing histomorphometry of myelinated axons. This allows quantification of demyelination proximal and remyelination distal to the crush site ex vivo and in vivo respectively. PMID- 22091450 TI - [Validation of the Argentine version of the Mood Disorder Questionnaire]. AB - Bipolar Disorder (BD) is a severe and recurrent medical illness with relevant impact on quality of life and functioning for patients. However, we still have significant deficits on its detection. One of the ways to improve the accurate recognition of the disease consists on the administration of screening tools such as the Mood Disorder Questionnaire (MDQ). The main aim of this investigation was to validate the Argentine version of the MDQ and determine the optimal cut off for outpatients who suffer from mood disorders in our country. The total sample consisted of 354 adult outpatients with diagnosis of BD type I, II and NOS, and Unipolar - Major Mood Disorders (MDD), enrolled between 2007 and 2008, from 11 sites of Argentina. The MDQ positively detected 53.6% of BD patients and 96.6% of MDD patients. The best cut off for our sample was established in 5 points for item 1 of the MDQ. By deleting the item 3 of the questionnaire, the performance was significantly improved. In conclusion, the Argentine version of the MDQ has demonstrated the same ability for detecting patients with BD of the English original version on a psychiatric population. PMID- 22091451 TI - [Some criminological and psychopathologic reflexions about serial crimes]. AB - This article reviews the concept of serial crime, including murder as well as any action for the purpose of inflicting bodily harm upon any person. It characterizes three types of multi-murderers: serial killers, mass murderers, and spree killers. These offenders often have a specific (ritual) behavior that is idiosyncratic and repeated on each crime, which allows the psychological profiling of the murderer. Examples, a psychopathological background, and a description of both their criminal behavior and dynamics are provided for each of these criminals. They are further classified according to their different motivations: psychotic, prophetic or enlightened, pleasure, secondary or pecuniary profits, power or control. Finally, the author shares his personal experience over 20 years in the assessment of sexual offenders. PMID- 22091452 TI - [Legal approach of antisocial personality disorders]. AB - We mention the different terms used over time to describe those behavioral disorders where prevailing selfishness, brutality, insensitivity, irresponsibility, manipulation and lack of empathy. It takes into account the biological, psychological and environmental theories. It refers to the importance of mirror neurons and its value in relation to the understanding of feelings. The criteria for the diagnosis, stressing the differences between psychopathic personalitya and antisocial personality disorder. Some sentences from different courts with various criteria are transcribed, for the apportionment or insanity of cases whose diagnosis is the psychopathic personality. Culminating with the legal approach of this type of personalities, from a civil and criminal perspective. PMID- 22091453 TI - [Filicide. Killer mothers]. AB - This paper aims to conduct a literature review of filicide and its various forms, placing the emphasis on the perpetrators, particularly in maternal filicide and the incidence of mental disorders in the perpetrators. It addresses the issue from the perspective of forensic psychiatrists, with input from a synthesis of two clinical trials of women charged for this crime, in which it arrived at the diagnosis of psychosis in one case and Munchausen syndrome in the other. PMID- 22091454 TI - [Vicissitudes of hospitalization and emergency in a Prison Psychiatric hospital]. AB - This paper evaluates the Reform of the Psychiatrist Central Ward for Men (Unit 20 of the Federal Prison System). The aim is to study the process of adopting a new paradigm for medically assisting psychiatric prisoner-patients and its consequences. It concludes that the medical condition of a psychiatric prisoner should be clarified and referred to the Department of Forensic Medicine by a Criminal Court straightaway, and that the Department of Forensic Medicine should act more promptly. It also suggests the relative reduction in working hours of both teams. PMID- 22091455 TI - [An approximation to the concepts of autonomy and integrity in clinical practice]. AB - This paper is about the interplay between autonomy and integrity in individuals in the context of the doctor-patient relationship. It analyses the concepts of autonomy, competence and rationality, related to the notion of individual integrity. It further provides a practical guide for the assessment of competence levels to be used by training doctors and therapists. PMID- 22091456 TI - [Psychiatric hospitalization for mental illness: past, present and future]. AB - The use of psychiatric hospitalization for mental illness has evolved through Modernity. In the last century, indefinite and involuntary committal was a widespread practice but has now become an extraordinary and short-term therapeutic recourse. Even though law experts, doctors and other mental health professionals agree on the benefits of this shift, in practice there are disagreements rooted in the shortcomings of health service providers. The current medical and legal criteria for hospitalization of patients with mental disorders should move away from the concept of endangerment and embrace therapeutic procedures and social care. New contemporary challenges, such as drugs and violence, require the implementation of a social strategy that is more comprehensive than medical treatment. This article presents a series of case studies describing the circumstances that led to the hospitalization of mental health patients, mostly in the city of Buenos Aires. PMID- 22091457 TI - [The first contribution of Psychiatry to Legal Medicine in Argentina]. PMID- 22091458 TI - Characterization of a novel Entamoeba histolytica strain from Burkina Faso, Africa, possessing a unique hexokinase-2 gene. AB - An Entamoeba histolytica strain (BF-841 cl1) that originated from Burkina Faso, Africa presented with novel, polymorphic genotypes of the serine-rich E. histolytica protein and the anodic hexokinase-2 (HXK-2) isoenzyme band, which showed less electrophoretic mobility than that of an E. histolytica reference strain [HM-1:IMSS cl6 (zymodeme (Z)-II)] by starch gel electrophoresis and isoelectric focusing (IEF). The HXK-2 gene of BF-841 cl1 had amino acid variations at four positions compared to the sequence of HM-1:IMSS cl6. These variations were absent from the sequences of four other E. histolytica strains with different zymodemes [KU27 (Z-II), SAW1627 (Z-IIa-), SAW755CR clB (Z-XIV), and KU2 (Z-XIX)]. The results of IEF showed no difference in the substrate specificity of HXK (HXK-1 and HXK-2) between BF-841 cl1 and the three reference E. histolytica strains (HM-1:IMSS cl6, SAW755 clB, and KU27). It was also confirmed that BF-841 cl1 was able to form liver abscesses in Syrian hamsters. PMID- 22091459 TI - Experimental evaluation of xenodiagnosis to detect trypanosomes at low parasitaemia levels in infected hosts. AB - In Human African Trypanosomosis (HAT) endemic areas, there are a number of subjects that are positive to serological tests but in whom trypanosomes are difficult to detect with the available parasitological tests. In most cases and particularly in West Africa, these subjects remain untreated, thus posing a fundamental problem both at the individual level (because of a possible lethal evolution of the disease) and at the epidemiological level (since they are potential reservoirs of trypanosomes). Xenodiagnosis may constitute an alternative for this type of cases. The objective of this study was to update the use of xenodiagnosis to detect trypanosomes in infected host characterized by low parasitaemia levels. This was carried out experimentally by infecting cattle and pigs with Trypanosoma congolense and T. brucei gambiense respectively, and by feeding tsetse flies (Glossina morsitans submorsitans and G. palpalis gambiensis, from the CIRDES colonies) on these animals at a time when the observed blood parasitaemia were low or undetectable by the classical microscopic parasitological tests used for the monitoring of infected animals. Our results showed that: i) the G. p. gambiensis colony at CIRDES could not be infected with the T. b. gambiense stocks used; ii) midgut infections of G. m. submorsitans were observed with both T. congolense and T. b. gambiense; iii) xenodiagnosis remains positive even at very low blood parasitaemia for both T. congolense and T. b. gambiense; and iv) to implement T. b. gambiense xenodiagnosis, batches of 20 G. m. submorsitans should be dissected two days after the infective meal. These results constitute a first step toward a possible implementation of xenodiagnosis to better characterize the parasitological status of seropositive individuals and the modalities of parasite transmission in HAT foci. PMID- 22091460 TI - [Entomological survey in the historical focus of human African trypanosomiasis of Bendje (Gabon)]. AB - The situation of human African trypanosomiasis (sleeping sickness) is poorly known in Gabon. Most of the historical foci have not been investigated for more than 15 years. Few cases are passively recorded from the historical focus of Bendje; they involved mainly fishermen but determining their contamination site is difficult because of their mobility due to their activity. The presence of these cases in that focus could favour its reactivation if the vector is still there. In order to assess a potential transmission risk in that area, an entomological survey has been carried out in it. Traps were set up during four days in different habitats used by humans during their daily activities. Three species of tsetse flies (Glossina palpalis palpalis, G. pallicera newsteadi and G. caliginea) were caught and two species of trypanosomes (Trypanosoma vivax and T. brucei s.l.) were identified by PCR. These results suggest the presence of an animal transmission cycle. Human-flies contact was confirmed in all type of habitats but no transmission was quantified in the mangrove. PMID- 22091461 TI - [Comparative safety study of two commercialised vaccines against canine babesiosis induced by Babesia canis]. AB - The safety of two vaccines available on the French market against canine babesiosis - Nobivac Piro(r) (NP) and Pirodog(r) (P) - have been evaluated. Their local, general and biochemical impacts have been compared in a controlled experimental study. Three groups were used: a control group (T) and two groups vaccinated twice at 21 days interval. All dogs presented moderate local reaction. However, either clinical and biological parameters showed that the NP group presented a significantly more intense reaction at the injection site compared to the P group. No statistical difference has been revealed between the groups P and T evolutions. PMID- 22091462 TI - Study of the sustained speed of kill of the combination of fipronil/amitraz/(S) methoprene and the combination of imidacloprid/permethrin against Dermacentor reticulatus, the European dog tick. AB - The sustained speed of kill against Dermacentor reticulatus of two topical combinations, one containing fipronil/amitraz/(S)-methoprene and the other, imidacloprid/permethrin, was evaluated in dogs. Two treated groups and one untreated control group of eight adult Beagle dogs each were randomly formed based on pre-infestation rates and bodyweight. Each treatment was administered topically once on Day 0, according to the recommended label dose and instructions for use. All dogs were infested with 50 adult unfed D. reticulatus starting on Day 1, then weekly, for a total of five weeks. While most studies determine tick efficacy at 48 hours (h), in this study, all remaining ticks were counted and categorized 24 h following each infestation. The numbers of ticks (living or dead) that remained attached on treated dogs were compared to those on the control animals. The percent reduction of attached ticks (disruption of attachment) at 24 h on dogs treated with fipronil/amitraz/(S)-methoprene remained above 92% for four weeks. The reduction of attached ticks at 24 h on dogs treated with imidacloprid/permethrin did not reach 80% during the entire study. The number of ticks attached at 24 h was significantly (p<0.05) lower in the fipronil/amitraz/(S)-methoprene group than in the imidacloprid/permethrin group in assessments on Days 2, 15, 22, 29 and 36. When assessing efficacy based upon live ticks on treated versus control dogs, fipronil/amitraz/(S)-methoprene 24 h efficacy was above 95% for four weeks, decreasing to 77.8% at Day 36. The 24 h efficacy of imidacloprid/permethrin ranged from 56.2% to 86.7% through Day 29, never achieving 90% throughout the study. The 24-hour efficacy of fipronil/amitraz/(S)-methoprene was significantly (p<0.05) higher than imidacloprid/permethrin at all time points, including Day 36. PMID- 22091463 TI - Comparative efficacy on dogs of a single topical treatment with the pioneer fipronil/(S)-methoprene and an oral treatment with spinosad against Ctenocephalides felis. AB - In the study reported here, the pioneer fipronil/(S)-methoprene topical product (Frontline(r) Plus, Merial Limited, Duluth, GA) was compared to the oral spinosad product (Comfortis(r) Elanco, Greenfield, IN) for efficacy against adult fleas and preventing egg production. The product presentations, doses and labelling were the one applicable in the USA. Using a standard protocol, 200 cat fleas of mixed sex were applied to dogs on Days 1, 7, 14, 21, 28, 35, and 42. Dogs were combed to remove fleas 24 hours post-infestation, the fleas were counted, collected, and then reapplied to each dog following completion of their respective count. At 48 hours post-infestation, comb counts were performed and fleas were removed. No fleas were collected from any dog in the fipronil/(S) methoprene group at any 24 or 48 hours post-infestation assessment throughout the six weeks study, yielding a preventive efficacy of 100%. For the spinosad treatment, efficacy was 100% at 24 hours and 48 hours through Day 16, and thereafter declined. The results observed in the spinosad-treated dogs were highly variable between animals. At the 24 and 48 hours counts following the Day 21 infestation, only five of eight spinosad-treated dogs (62.5%) were flea-free. Following the Day 28 infestation, spinosad efficacy fell to 85% and 89%, for the 24 hours and 48 hours counts, and only two dogs (25%) were flea free, compared to 100% flea-free dogs in the fipronil/(S)-methoprene group. No fleas were collected from the fipronil/(S)-methoprene treated dogs throughout the entire study, therefore, no eggs were collected at any time from any dog in the group. However, in the spinosad group adult fleas were found on dogs starting on Day 21 and by Day 30, 42 eggs were collected from one dog that had 107 adult fleas counted at 48 hours. At Day 37 and Day 49, more than 100 eggs were collected from each dog in the spinosad-treated and control groups. PMID- 22091464 TI - Antileishmanial activity of a formulation of 2-n-propylquinoline by oral route in mice model. AB - 2-n-propylquinoline is presently a drug-candidate for the treatment of visceral leishmaniosis in pre-clinical development. As this compound is in an oily state, it needs to be formulated and the objectives of this study are: to prepare a formulation; to demonstrate that the new salted formulation did not alter the activity of the active ingredient; and finally, that this activity was quite good compared to the reference oral drug, miltefosine. Therefore, a 2-n propylquinoline formulation, as camphorsulfonic salt, was prepared and characterised. On the Leishmania donovani / Balb/c mice model, a treatment by oral route at 60 mmoles/kg/day for ten consecutive days with this formulation was compared to 2-n-propylquinoline alone and to miltefosine, the oral reference drug. The salt formulation did not alter the activity of the 2-n-propylquinoline. The formulation reduced the parasite burden of 76% compared to 89% for miltefosine (not significant). The characteristics of this formulation results in a suitable drugability of 2-n-propylquinoline for further studies. PMID- 22091465 TI - Record of Phlebotomus (Transphlebotomus) mascittii Grassi, 1908 and Phlebotomus (Larroussius) chadlii Rioux, Juminer & Gibily, 1966 female in Algeria. AB - We report for the first time the presence of Phlebotomus mascittii and the female of Phlebotomus chadlii in Algeria. These two species were collected during an entomological study conducted in endemic visceral leishmaniasis focus from the north part of the country, Kabylia. PMID- 22091466 TI - Recovery of DNA of Giardia intestinalis cysts from surface water concentrates measured with PCR and real time PCR. AB - The most important restriction for the detection in water samples is the low concentration of Giardia intestinalis cysts, additional difficulty is the presence of PCR inhibitors. We have carried out trials in order to assess the sensitivity of semi-nested PCR and TaqMan real time PCR on the basis of DNA extracted from G. intestinalis cysts coming from spiked environmental and distilled water samples, filtrated with the use of Filta-Max(r) equipment (1623 Method). Removal of inhibitors was carried out with addition of BSA in different concentrations. During the filtration and concentration of water samples, losses of cysts have been recorded. Moreover, addition of BSA to the PCR and real time PCR mix increases the sensitivity of reaction. The optimal concentration of BSA for semi-nested PCR was 15 and 20 ng/MUl, whereas for real time PCR 5 ng/MUl. PMID- 22091467 TI - Toxoplasma gondii in wild and domestic animals from New Caledonia. AB - Samples (serum or meat juice) collected from 205 animals in New Caledonia in April 2009 were tested for antibodies against Toxoplasma gondii by ELISA using the multi-species ID Screen(r) Toxoplasmosis Indirect kit (IDVET, Montpellier). Antibodies to T. gondii were detected in 2% (1/49) of the pigs, in 3.3% (1/30) of the cattle, in 13.8% (4/29) of Rusa deers, in 16% (4/25) of the horses, in 32.8% (21/64) of the dogs, and in 50% (4/8) of cats. Statistically, no significant difference was observed between T. gondii seroprevalence and age or sex. No survey on the prevalence of T. gondii in animals has ever been conducted in New Caledonia and this is the first serological evidence of T. gondii in Rusa deer (Cervus timorensis russa). These results indicate an important circulation of T. gondii exists in the animal populations of New Caledonia. In view of humans being exposed, it is advisable to insist on sanitary education and on respect for good hygienic and food practice. PMID- 22091468 TI - Seroprevalence of Neospora caninum in dairy cattle from north-west and centre of Romania. AB - Neosporosis is a disease that mainly affects cattle in both dairy and beef herds. The main definitive host of this parasite is the dog. Since 1984 and its first description a large number of data were published worldwide on this parasite. In Romania, the research regarding this parasite is limited. The purpose of this study was to determine the seroprevalence of Neospora caninum infection in dairy cattle from six regions in north-western Romania and to evaluate the intensity of infection in different animals groups. A total number of 901 samples (862 sera from adult cows and 39 sera from calves) were collected from dairy farms and were screened for the presence of specific IgG anti-bodies using an enzyme-linked immunosorbent assay (ELISA). The overall seroprevalence for neosporosis was 34.6%. In adult cows and calves seroprevalences reached 34.8% (300/862) and 30.8% for calves (12/39) respectively. In cattle which had previously aborted, seroprevalence was 40.9%. These results indicate that N. caninum infection is widespread among animals reared in dairy systems from Romania and a program for farmer training and a strategy for reducing the economic impact of the disease are needed. PMID- 22091469 TI - Sensitive electrochemical immunosensor array for the simultaneous detection of multiple tumor markers. AB - A novel electrochemical immunosensor array for the simultaneous detection of multiple tumor markers was developed by incorporating electrochemically addressing immobilization and one signal antibody strategy. As a proof-of principle, an eight-electrode array including six carbon screen-printed working electrodes was used as a base array for the analysis of two important tumor markers, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) and a horseradish peroxidase-labeled antibody was employed as a signal antibody. The immunosensor in the array was fabricated in sequence by covalently coupling the capture antibody onto the surface of the desired working electrode, which was firstly electrochemically addressably grafted with an aminophenyl group by reduction of in situ generated aminophenyl diazonium cation generated from p phenylenediamine, using glutaraldehyde as cross-linker. This allowed the selective immobilization of the capture antibody at the desired position on a single array via an electrochemical operation. The immunoassay in sandwich mode was performed by specifically binding the targets, second antibodies and one signal antibody to the immunosensor array. The result showed that the steady current density was directly proportional to the concentration of target CEA/AFP in the range from 0.10 to 50 ng mL(-1) with a detection limit of 0.03 ng mL(-1) for CEA and 0.05 ng mL(-1) for AFP (S/N = 3), respectively. This work demonstrates that the employment of an electrochemically addressing method for the fabrication of an immunosensor array and one signal antibody is a promising approach for the determination of multiple tumor markers in clinical samples. PMID- 22091484 TI - Successful aging: development and testing of a multidimensional model using data from a large sample of older australians. AB - OBJECTIVES: To develop a multidimensional statistical model that could assess the contribution of, and interrelationships between, measures likely to contribute to an individual's successful aging, defined as aging well across a number of dimensions. DESIGN: Cross-sectional. SETTING: Data collected from 8,841 Australians aged 16 to 85 during the 2007 National Survey of Mental Health and Well-Being conducted by the Australian Bureau of Statistics. PARTICIPANTS: Two thousand two hundred eighty-six survey participants aged 61 to 85. MEASUREMENTS: Self-assessed physical and mental health, quality of life, and cognition constitute the outcome factor: successful aging. Attributes measuring past and current mental and physical health, social measures, and health behaviors were considered for inclusion as predictor measures. Results of the final model allowed calculation of individual weighted successful aging scores. RESULTS: The final model closely fitted responses from participants and men and women separately. Factors measuring mental and physical health and social support contributed significantly and independently to successful aging. Health behaviors, measuring extent of physical exercise and not smoking, contributed to successful aging in addition to their association with physical health. On average, those scoring in the highest decile of the successful aging measure reported having two chronic health conditions, indicating that such conditions do not necessarily preclude high levels of well-being in older individuals. CONCLUSION: This model developed from a large sample of older individuals identified factors worth targeting in future social and health policy initiatives for this age group. It also indicates that chronic illness is not necessarily a barrier to successful aging. PMID- 22091485 TI - Robust monomer-distribution biosignatures in evolving digital biota. AB - Because organisms synthesize component molecules at rates that reflect those molecules' adaptive utility, we expect a population of biota to leave a distinctive chemical signature on its environment that is anomalous given the local (abiotic) chemistry. We observe the same effect in the distribution of computer instructions used by an evolving population of digital organisms, and we characterize the robustness of the evolved signature with respect to a number of different changes in the system's physics. The observed instruction abundance anomaly has features that are consistent over a large number of evolutionary trials and alterations in system parameters, which makes it a candidate for a non Earth-centric life diagnostic. PMID- 22091486 TI - The O/OREOS mission: first science data from the Space Environment Survivability of Living Organisms (SESLO) payload. AB - We report the first telemetered spaceflight science results from the orbiting Space Environment Survivability of Living Organisms (SESLO) experiment, executed by one of the two 10 cm cube-format payloads aboard the 5.5 kg Organism/Organic Exposure to Orbital Stresses (O/OREOS) free-flying nanosatellite. The O/OREOS spacecraft was launched successfully to a 72 degrees inclination, 650 km Earth orbit on 19 November 2010. This satellite provides access to the radiation environment of space in relatively weak regions of Earth's protective magnetosphere as it passes close to the north and south magnetic poles; the total dose rate is about 15 times that in the orbit of the International Space Station. The SESLO experiment measures the long-term survival, germination, and growth responses, including metabolic activity, of Bacillus subtilis spores exposed to the microgravity, ionizing radiation, and heavy-ion bombardment of its high inclination orbit. Six microwells containing wild-type (168) and six more containing radiation-sensitive mutant (WN1087) strains of dried B. subtilis spores were rehydrated with nutrient medium after 14 days in space to allow the spores to germinate and grow. Similarly, the same distribution of organisms in a different set of microwells was rehydrated with nutrient medium after 97 days in space. The nutrient medium included the redox dye Alamar blue, which changes color in response to cellular metabolic activity. Three-color transmitted intensity measurements of all microwells were telemetered to Earth within days of each of the 48 h growth experiments. We report here on the evaluation and interpretation of these spaceflight data in comparison to delayed-synchronous laboratory ground control experiments. PMID- 22091487 TI - Who values information from a health plan Internet-based decision tool and why: a demographic and utilization analysis. AB - OBJECTIVES: The aim of this study was to investigate factors associated with utilization of health plan Internet-based decision tools. DATA SOURCES AND STUDY SETTING: Enrollment, claims, plan design, and web transaction data during 2008 provided by a national health insurer for 253,398 subscribers from 919 employers. STUDY DESIGN: Multivariate models of the effects of demographic, health, employer, and plan benefit design characteristics on the use of the tool and its individual function categories. DATA EXTRACTION METHODS: Subscribers, who were either an individual member or a family, were included if at least one family member had 12 months of coverage in 2008. Members older than 65 and those with multiple insurance carriers were excluded. PRINCIPAL FINDINGS: Higher education, higher income, younger age, female gender, higher co-morbidity risk, prevalence of chronic conditions, Caucasian race, and English as the primary language were positively associated with using the tool. Plan benefit characteristics such as free preventive coverage, higher deductible, moderate coinsurance rate, family coverage, and enrollment in health savings accounts were also associated with higher likelihood of using the tool. CONCLUSIONS: Insurers provide consumers information on cost efficiency, quality, and wellness through Internet-based decision tools, but more effort is needed to reach certain demographics. PMID- 22091488 TI - Positive intelligence illusions: on the relation between intellectual self enhancement and psychological adjustment. AB - The relation between self-enhancement and psychological adjustment has been debated for over 2 decades. This controversy is partly due to the variety of approaches implicated in the assessment of mainly self-enhancement but also psychological adjustment. We adopted a face-valid approach by statistically removing actual intellectual ability variance from self-rated intellectual ability variance. Study 1 (N = 2,048), a concurrent Internet investigation, provided initial insight into the relation between intellectual self-enhancement and psychological adjustment. Study 2 (N = 238), a longitudinal round-robin investigation, allowed a closer examination of the dynamic processes underlying this relation. Self-enhancement was positively linked to multiple indicators of intrapersonal and interpersonal adjustment, and predicted rank-order increases in adjustment over time. The links between intellectual self-enhancement and intrapersonal adjustment were mediated by self-esteem. Finally, the interpersonal costs and benefits of self-enhancement systematically varied depending on methodology. PMID- 22091489 TI - Resection of Grade III cranial horn tears of the equine medial meniscus alter the contact forces on medial tibial condyle at full extension: an in-vitro cadaveric study. AB - OBJECTIVE: To evaluate the magnitude and distribution of joint contact pressure on the medial tibial condyle after grade III cranial horn tears of the medial meniscus. STUDY DESIGN: Experimental study. ANIMALS: Cadaveric equine stifles (n = 6). METHODS: Cadaveric stifles were mounted in a materials testing system and electronic pressure sensors were placed between the medial tibial condyle and medial meniscus. Specimens were loaded parallel to the longitudinal axis of the tibia to 1800 N at 130 degrees , 140 degrees , 150 degrees , and 160 degrees stifle angle. Peak pressure and contact area were recorded from the contact maps. Testing was repeated after surgical creation of a grade III cranial horn tear of the medial meniscus, and after resection of the simulated tear. RESULTS: In the intact specimens, a significantly smaller contact area was observed at 160 degrees compared with the other angles (P < .05). Creation of a grade III cranial horn tear in the medial meniscus did not significantly alter the pressure or contact area measurements at any stifle angle compared with intact specimens (P > .05). Resection of the tear resulted in significantly higher peak pressures in the central region of the medial tibial condyle at a stifle angle of 160 degrees relative to the intact (P = .026) and torn (P = .012) specimens. CONCLUSIONS: Resection of grade III cranial horn tears in the medial meniscus resulted in a central focal region of increased pressure on the medial tibial condyle at 160 degrees stifle angle. PMID- 22091490 TI - Association between serum cholesterol and noncardiovascular mortality in older age. AB - OBJECTIVES: To clarify the association between cholesterol and noncardiovascular mortality and to evaluate how this association varies across age groups. DESIGN: Prospective population-based cohort study. SETTING: Rotterdam, the Netherlands. PARTICIPANTS: Adults aged 55 to 99 (N = 5,750). MEASUREMENTS: Participants were evaluated for total cholesterol and subfractions and followed for mortality for a median of 13.9 years. Total cholesterol and its subfractions were evaluated in relation to noncardiovascular mortality. Cox regression analyses were conducted in the total sample and within age-groups (55-64, 65-74, 75-84, >=85). RESULTS: Age- and sex-adjusted analyses showed that each 1-mmol/L increase in total cholesterol was associated with an approximately 12% lower risk of noncardiovascular mortality (hazard ratio (HR) = 0.88, 95% confidence interval (CI) = 0.84-0.92, P < .001). Age group-specific analyses demonstrated that this association reached significance after the age of 65 and increased in magnitude across each subsequent decade. This was driven largely by non-high-density lipoprotein cholesterol (non-HDL-C) (HR = 0.89, 95% CI 0.85-0.93, P < .001) and was partly attributable to cancer mortality. Conversely, HDL-C was not significantly associated with noncardiovascular mortality (HR = 0.92, 95% CI 0.79 1.07, P = .26). CONCLUSION: Higher total cholesterol was associated with a lower risk of noncardiovascular mortality in older adults. This association varied across the late-life span and was stronger in older age groups. Further research is required to examine the mechanisms underlying this association. PMID- 22091491 TI - Relationship between vitamin D and hyperglycemia in older people from a nationally representative population survey. AB - OBJECTIVES: To investigate the association between vitamin D levels and hyperglycemia in a national community sample of older people. DESIGN: Cross sectional, nationally representative sample. SETTING: Community. PARTICIPANTS: Two thousand thirty-eight noninstitutitionalized adults aged 65 and older taking part in the Health Survey for England 2005. MEASUREMENTS: Serum 25-hydroxy vitamin D (25(OH) D) levels, glycosylated hemoglobin (HbA1c), and covariates: age, sex, social class, season of examination, use of vitamin supplements, and physical health status. RESULTS: Hyperglycemia was independently associated with low vitamin D levels (odds ratio (OR) = 2.30, 95% confidence interval (CI) = 1.20 4.42 for 25(OH)D <25.0 nmol/L and OR = 2.09, 95% CI = 1.22-3.58 for 25(OH)D 25.0 49.9 nmol/L) but not for 25(OH)D between 50.0 and 74.9 nmol/L (OR = 1.49, 95% CI = 0.85-2.62). CONCLUSION: The higher-than-expected co-occurrence of low vitamin D levels and hyperglycemia (HbA1c >= 6.5%) are important public health concerns for older populations living in northern latitudes because both are common, and both have substantial adverse health consequences. Ensuring adequate vitamin D levels may help reverse the increasing trend in the development of diabetes mellitus and related complications in older people. PMID- 22091494 TI - Quality of care provided in a special needs plan using a nurse care manager model. AB - OBJECTIVES: To comprehensively evaluate the quality of care provided in special needs plans (SNPs; Medicare Advantage plans that aim to provide specialized care for complex older adults) and specifically the nurse care management model in the community setting. DESIGN: We adapted 107 process-of-care quality measures across 12 conditions from the Assessing Care of Vulnerable Elders set to obtain a clinically detailed evaluation of the quality of care received by complex older enrollees in a dual eligible Evercare SNP. We abstracted 13 months of primary care medical records to delineate quality of care provided by physicians and whether there was value added from the nurse care manager model. SETTING: Dual eligible Evercare SNP located in central Florida. PARTICIPANTS: Two-hundred thirty-one vulnerable older enrollees in the SNP who had complex disease. RESULTS: Based on physician medical records alone, the 231 high-risk participants (mean age 77, 67% women) received recommended care for 53% of 5,569 evaluated clinical circumstances, ranging from 12% for end-of-life care to 78% for diabetes mellitus. In fewer than 40% of these clinical circumstances was recommended care provided for dementia, falls, and urinary incontinence. In a second analysis accounting for care provided by both the Evercare nurse and the physician, recommended care was provided to patients in 69% of the 5,684 evaluated clinical circumstances. CONCLUSION: Comprehensive quality measurement applied to vulnerable older adults enrolled in one mature SNP showed that the Evercare nurse model addresses important deficits in physician care for geriatric conditions. Such measurement should be applied to other SNP models and to compare SNP care with that for complex, older, fee-for-service Medicare cohorts. PMID- 22091492 TI - Serum 25-hydroxyvitamin D and physical function in older adults: the Cardiovascular Health Study All Stars. AB - OBJECTIVES: To examine the association between 25-hydroxyvitamin D (25(OH)D) and physical function in adults of advanced age. DESIGN: Cross-sectional and longitudinal analysis of physical function over 3 years of follow-up in the Cardiovascular Health Study All Stars. SETTING: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania. PARTICIPANTS: Community-dwelling adults aged 77 to 100 (N = 988). MEASUREMENTS: Serum 25-hydroxyvitamin D 25(OH)D), Short Physical Performance Battery (SPPB), and grip and knee extensor strength assessed at baseline. Mobility disability (difficulty walking half a mile or up 10 steps) and activities of daily living (ADLs) disability were assessed at baseline and every 6 months over 3 years of follow-up. RESULTS: Almost one-third (30.8%) of participants were deficient in 25(OH)D (<20 ng/mL). SPPB scores were lower in those with deficient 25(OH)D (mean (standard error) 6.53 (0.24)) than in those with sufficient 25(OH)D (>=30 ng/mL) (7.15 (0.25)) after adjusting for sociodemographic characteristics, season, health behaviors, and chronic conditions (P = .006). Grip strength adjusted for body size was also lower in those with deficient 25(OH)D than in those with sufficient 25(OH)D (24.7 (0.6) kg vs 26.0 (0.6) kg, P = .02). Participants with deficient 25(OH)D were more likely to have prevalent mobility (OR = 1.44, 95% confidence interval (CI)) = 0.96-2.14) and ADL disability (OR = 1.51, 95% CI = 1.01-2.25) at baseline than those with sufficient 25(OH)D. Furthermore, participants with deficient 25(OH)D were at greater risk of incident mobility disability over 3 years of follow-up (hazard ratio = 1.56, 95% CI = 1.06-2.30). CONCLUSION: Vitamin D deficiency was common and was associated with poorer physical performance, lower muscle strength, and prevalent mobility and ADL disability in community-dwelling older adults. Moreover, vitamin D deficiency predicted incident mobility disability. PMID- 22091493 TI - Categorizing the effect of comorbidity: a qualitative study of individuals' experiences in a low-vision rehabilitation program. AB - OBJECTIVES: To identify generalizable ways that comorbidity affects older adults' experiences in a health service program directed toward an index condition and to develop a framework to assist clinicians in approaching comorbidity in the design, delivery, and evaluation of such interventions. DESIGN: A qualitative data content analysis of interview transcripts to identify themes related to comorbidity. SETTING: An outpatient low-vision rehabilitation program for macular disease. PARTICIPANTS: In 2007/08, 98 individuals undergoing low-vision rehabilitation and their companions provided 624 semistructured interviews that elicited perceptions about barriers and facilitators of successful program participation. RESULTS: The interviews revealed five broad themes about comorbidity: (i) "good days, bad days," reflecting participants' fluctuating health status during the program because of concurrent medical problems; (ii) "communication barriers." which were sometimes due to participant impairments and sometimes situational; (iii) "overwhelmed," which encompassed pragmatic and emotional concerns of participants and caregivers; (iv) "delays," which referred to the tendency of comorbidities to delay progress in the program and to confer added inconvenience during lengthy appointments; and (v) value of companion involvement in overcoming some barriers imposed by comorbid conditions. CONCLUSION: This study provides a taxonomy and conceptual framework for understanding consequences of comorbidity in the experience of individuals receiving a health service. If confirmed in individuals receiving interventions for other index diseases, the framework suggests actionable items to improve care and facilitate research involving older adults. PMID- 22091495 TI - Differences in mortality associated with dementia in U.S. blacks and whites. AB - OBJECTIVES: To test the hypothesis that the geographic pattern of mortality with dementia coded on the death certificate varies according to race and that racial differences vary according to geography in the United States. DESIGN: Analysis of the U.S. multiple-cause-of-death files for 1999 to 2004. SETTING: United States. PARTICIPANTS: Decedents with dementia coded as underlying or contributing cause of death on the death certificate. MEASUREMENTS: Age-adjusted death rates for U.S. Census geographic divisions for blacks and whites aged 65 and older. RESULTS: From 1999 to 2004, the U.S. age-adjusted annual death rate per 100,000 for dementia was 628 in blacks and 647 in whites. The difference between rates in blacks and whites ranged from -130 deaths per 100,000 (-36%) in the Middle Atlantic region to +55 (+8%) in the South Atlantic division. Blacks had higher rates in three divisions and whites in five. In the Middle Atlantic and in the United States as a whole, blacks were relatively more likely to receive a diagnosis of unspecified dementia or senility (66%) than Alzheimer's disease (30%) than whites (58% and 41%, respectively). CONCLUSION: Although overall rates were similar, geographic variation in racial differences in rates of death with dementia occurred between U.S. regions. Further research is needed to assess geographic and racial variation in artifacts of certification versus biological variation as possible causes of variation to enhance utility of mortality data for disease monitoring and health-disparities research. PMID- 22091496 TI - Subsyndromal delirium in older long-term care residents: incidence, risk factors, and outcomes. AB - OBJECTIVES: To determine the incidence of, risk factors for, and outcomes of subsyndromal delirium (SSD) in older long-term care (LTC) residents and, secondarily, to explore the use of a more-restrictive definition of SSD. DESIGN: Cohort study with repeated weekly assessments for up to 6 months. SETTING: Seven LTC facilities in Montreal and Quebec City, Canada. PARTICIPANTS: One hundred four LTC residents aged 65 and older and free of delirium core symptoms at baseline. MEASUREMENTS: The Mini-Mental State Examination (MMSE), Confusion Assessment Method (CAM), Delirium Index (DI), Hierarchic Dementia Scale (HDS), and Barthel Index (BI) were completed at baseline. The MMSE, CAM, and DI were repeated weekly for 6 months. SSD1 required one or more CAM core symptoms; SSD2, a more-restrictive definition, required two or more CAM core symptoms. Outcomes at 6 months were decline on the MMSE, HDS, and BI; mortality; and a composite outcome. RESULTS: Sixty-eight of 104 residents had SSD1. In survival analysis, the incidence was 5.2 (95% confidence interval (CI) = 4.1-6.7) per 100 person weeks of follow-up. In multivariate analysis, risk factors were male sex and more severe cognitive impairment at baseline. The differences in outcomes between residents with and without SSD1 were small and not statistically significant. SSD2 had a lower incidence (1.3, 95% CI = 0.9-1.9), similar risk factors, and statistically significantly worse cognitive outcomes. CONCLUSION: SSD2 appears to be a clinically important disorder in older LTC residents. Despite limited statistical power, these findings have potentially important implications for clinical practice and research in LTC settings. PMID- 22091497 TI - The feasibility of inpatient geriatric assessment for older adults receiving induction chemotherapy for acute myelogenous leukemia. AB - OBJECTIVES: To test the feasibility and utility of a bedside geriatric assessment (GA) to detect impairment in multiple geriatric domains in older adults initiating chemotherapy for acute myelogenous leukemia (AML). DESIGN: Prospective observational cohort study. SETTING: Single academic institution. PARTICIPANTS: Individuals aged 60 and older with newly diagnosed AML and planned chemotherapy. MEASUREMENTS: Bedside GA was performed during inpatient exmination for AML. GA measures included the modified Mini-Mental State Examination; Center for Epidemiologic Studies Depression Scale; Distress Thermometer, Pepper Assessment Tool for Disability (includes self- reported activities of daily living (ADLs), instrumental ADLs, and mobility questions); Short Physical Performance Battery (includes timed 4-m walk, chair stands, standing balance); grip strength, and Hematopoietic Cell Transplantation Comorbidity Index. RESULTS: Of 54 participants (mean age 70.8 +/- 6.4) eligible for this analysis, 92.6% completed the entire GA battery (mean time 44.0 +/- 14 minutes). The following impairments were detected: cognitive impairment, 31.5%; depression, 38.9%; distress, 53.7%; impairment in ADLs, 48.2%; impaired physical performance, 53.7%; and comorbidity, 46.3%. Most were impaired in one (92.6%) or more (63%) functional domains. For the 38 participants rated as having good performance status according to standard oncologic assessment (Eastern Cooperative Oncology Performance Scale score <=1), impairments in individual GA measures ranged from 23.7% to 50%. Significant variability in cognitive, emotional, and physical status was detected even after stratification according to tumor biology (cytogenetic risk group classification). CONCLUSION: Inpatient GA was feasible and added new information to standard oncology assessment, which may be important for stratifying therapeutic risk in older adults with AML. PMID- 22091498 TI - Staging the severity of chronic obstructive pulmonary disease in older persons based on spirometric Z-scores. AB - OBJECTIVES: Among older persons, the use of spirometric Z-scores as calculated by the Lambda-Mu-Sigma (LMS) method has a strong scientific rationale for establishing a diagnosis of chronic obstructive pulmonary disease (COPD), but its clinical validity in staging COPD severity is not yet known. The current study has therefore evaluated the association between LMS-staged COPD and health outcomes, in two separate cohorts of older persons. DESIGN: Longitudinal cohort study. SETTING: The Cardiovascular Health Study (CHS, N = 3,248) and the Third National Health and Nutrition Examination Survey (NHANES-III, N = 1,354). PARTICIPANTS: Community-living white participants aged 65 to 80. MEASUREMENTS: Using spirometric data, COPD was staged as mild, moderate, or severe based on LMS derived Z-scores. Clinical validity was then evaluated according to all-cause mortality, respiratory symptoms (chronic bronchitis, dyspnea, or wheezing), and moderate to severe dyspnea (available in CHS only). RESULTS: In CHS, the LMS staging of COPD as mild, moderate, and severe was associated with mortality (adjusted HR (aHR) = 1.50, 95% confidence interval (CI) = 1.15-1.94; aHR = 1.31, 95% CI = 1.03-1.67; and aHR = 2.00, 95% CI = 1.70-2.36, respectively) and with respiratory symptoms (adjusted OR (aOR) = 1.69, 95% CI = 1.12-2.56; aOR = 1.87, 95% CI = 1.28-2.73; and aOR = 3.99, 95% CI = 2.91-5.48, respectively). Also in CHS, moderate and severe, but not mild, LMS-staged COPD was associated with moderate to severe dyspnea (aOR = 2.16, 95% CI = 1.24-3.75; aOR = 3.98, 95% CI = 2.77-5.74; and aOR = 0.84, 95% CI = 0.35-2.01, respectively). Similar associations were found for mortality and respiratory symptoms in NHANES-III, except mild severity was not associated with mortality (aHR = 0.93, 95% CI = 0.62 1.40). CONCLUSION: In white older persons, the spirometric staging of COPD severity based on LMS-derived Z-scores was associated with several clinically relevant health outcomes. These results support the use of the LMS method for staging the severity of COPD in older populations. PMID- 22091500 TI - Emergency department visits by nursing home residents in the United States. AB - OBJECTIVES: To characterize emergency department (ED) use by nursing home residents in the United States. DESIGN: Analysis of the National Hospital Ambulatory Medical Care Survey. SETTING: U.S. EDs from 2005 to 2008. PARTICIPANTS: Individuals visiting U.S. EDs stratified according to nursing home residency. MEASUREMENTS: All ED visits by nursing home residents were identified. The demographic and clinical characteristics and ED resource utilization, length of stay, and outcomes of nursing home residents and nonresidents were compared. RESULTS: During 2005 to 2008, nursing home residents accounted for 9,104,735 of 475,077,828 U.S. ED visits (1.9%; 95% confidence interval (CI) = 1.8-2.1%). The annualized number of ED visits by nursing home residents was 2,276,184. Most nursing home residents were older (mean age 76.7, 95% CI = 75.8-77.5), female (63.3%), and non-Hispanic white (74.8%). Nursing home residents were more likely to have been discharged from the hospital in the prior 7 days (adjusted odds ratio (aOR = 1.4, 95% CI = 1.1-1.9), to present with fever (aOR = 1.9, 95% CI = 1.5-2.4) or hypotension (systolic blood pressure <=90 mmHg, aOR = 1.8, 95% CI = 1.5-2.2), and to receive diagnostic tests (OR = 1.9, 95% CI = 1.6-2.2), imaging (OR = 1.5, 95% CI = 1.3-1.7), or procedures (OR = 1.6, 95% CI = 1.4-1.7) in the ED. Almost half of nursing home residents visiting the ED were admitted to the hospital. Nursing home residents were more likely to be admitted to the hospital (aOR = 1.8, 95% CI = 1.6-2.0) and to die (aOR = 2.3, 95% CI = 1.6-3.3). CONCLUSION: Nursing home residents account for more than 2.2 million ED visits annually in the United States. Nursing home residents have greater medical acuity and complexity. These observations highlight the national challenges of organizing and delivering ED care to nursing home residents in the United States. PMID- 22091499 TI - Lower extremity nerve function, calf skeletal muscle characteristics, and functional performance in peripheral arterial disease. AB - OBJECTIVES: To determine whether poor lower extremity nerve function is associated with less-favorable calf muscle characteristics and greater functional impairment in people with and without peripheral arterial disease (PAD). DESIGN: Cross-sectional. SETTING: Three Chicago-area medical centers. PARTICIPANTS: Four hundred thirteen participants with PAD (ankle-brachial index (ABI) < 0.90) and 255 without. MEASUREMENTS: Electrodiagnostic testing of the peroneal nerve was performed. Calf muscle cross-sectional area and percentage fat were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Six-minute walk performance was measured. RESULTS: Adjusting for age, sex, race, ABI, leg symptoms, smoking, physical activity, comorbidities, and other covariates, lower peroneal nerve conduction velocity (NCV) was associated with lower calf muscle area (first quartile 4,770.3 mm(2) , fourth quartile 5,571 mm(2) , P < .001) and poorer 6-minute walk distance (first quartile 989.2 feet, fourth quartile 1,210.8 feet, P < .001) in participants without diabetes mellitus with PAD. Lower peroneal NCV was associated with lower calf muscle area (first quartile 5,166.0 mm(2) , fourth quartile 6,003.8 mm(2) , P = .01) and poorer 6 minute walk distance (first quartile 866.4 feet, fourth quartile 1,082.5 feet, P = .01) in participants with diabetes mellitus and PAD as well. In participants without PAD, lower peroneal NCV was not associated with lower calf muscle area but was associated with poorer 6-minute walk distance only in participants without diabetes mellitus (first quartile 1,317.0 feet, fourth quartile 1,570.4 feet, P-trend < .001). CONCLUSION: Lower peroneal nerve function is associated with smaller calf muscle area and greater functional impairment in individuals with PAD. Future study is needed to determine whether improving peroneal NCV prevents loss of calf muscle and functional decline in people with PAD. PMID- 22091501 TI - Sustaining clinical programs during difficult economic times: a case series from the Hospital Elder Life Program. AB - OBJECTIVES: To explore strategies used by clinical programs to justify operations to decision-makers using the example of the Hospital Elder Life Program (HELP), an evidence-based, cost-effective program to improve care for hospitalized older adults. DESIGN: Qualitative study design using 62 in-depth, semistructured interviews conducted with HELP staff members and hospital administrators between September 2008 and August 2009. SETTING: Nineteen HELP sites in hospitals across the United States and Canada that had been recruiting patients for at least 6 months. PARTICIPANTS: HELP staff and hospital administrators. MEASUREMENTS: Participant experiences sustaining the program in the face of actual or perceived financial threats, with a focus on factors they believe are effective in justifying the program to decision-makers in the hospital or health system. RESULTS: Using the constant comparative method, a standard qualitative analysis technique, three major themes were identified across interviews. Each focuses on a strategy for successfully justifying the program and securing funds for continued operations: interact meaningfully with decision-makers, including formal presentations that showcase operational successes and informal means that highlight the benefits of HELP to the hospital or health system; document day-to day, operational successes in metrics that resonate with decision-maker priorities; and garner support from influential hospital staff that feed into administrative decision-making, particularly nurses and physicians. CONCLUSION: As clinical programs face financially challenging times, it is important to find effective ways to justify their operations to decision-makers. Strategies described here may help clinically effective and cost-effective programs sustain themselves and thus may help improve care in their institutions. PMID- 22091502 TI - Risk of fractures requiring hospitalization after an initial prescription for zolpidem, alprazolam, lorazepam, or diazepam in older adults. AB - OBJECTIVES: To determine whether zolpidem is a safer alternative to benzodiazepines. DESIGN: Retrospective cohort study. SETTING: Community based. PARTICIPANTS: Health maintenance organization members with an initial prescription for zolpidem (n = 43,343), alprazolam (n = 103,790), lorazepam (n = 150,858), or diazepam (n = 93,618). MEASUREMENTS: Zolpidem and benzodiazepine prescriptions were identified from pharmacy databases. Rates of nonvertebral fractures and hip fractures requiring hospitalization were compared before and after an initial prescription for each treatment, adjusting for confounders using doubly robust estimation. RESULTS: In patients aged 65 and older, the rates of nonvertebral fractures and dislocations were similar in the pre- treatment intervals. The rate ratios (RRs) for the 90-day posttreatment interval relative to the pretreatment interval were 2.55 (95% confidence interval (CI) = 1.78-3.65; P < .001) for zolpidem, 1.14 (95% CI = 0.80-1.64; P = .42) for alprazolam, 1.53 (95% CI = 1.23-1.91; P < .001) for lorazepam, and 1.97 (95% CI = 1.22-3.18; P = .01) for diazepam. The ratio of RRs (RRR)-the RR in the posttreatment period adjusted for the corresponding RR in the pretreatment period-were 2.23 (95% CI = 1.36-3.66; P = .006) for zolpidem relative to alprazolam, 1.68 (95% CI = 1.12 2.53; P = .02) for zolpidem relative to lorazepam, and 1.29 (95% CI = 0.72-2.30; P = .32) for zolpidem relative to diazepam. The RRs decreased with time from the initial prescription (trend P < .001), as would be expected if the association is causal. CONCLUSION: In older adults, the risk of injury with zolpidem exceeded that with alprazolam and lorazepam and was similar to that with diazepam. If the associations are causal, then the high incidence of these fractures implies that these treatment induce a substantial number of fractures and consequential costs. Further study of the association is imperative. PMID- 22091503 TI - Use of opioids or benzodiazepines and risk of pneumonia in older adults: a population-based case-control study. AB - OBJECTIVES: To examine whether use of opioids or benzodiazepines is associated with risk of community-acquired pneumonia in older adults. DESIGN: Population based case-control study. SETTING: An integrated healthcare delivery system. PARTICIPANTS: Community-dwelling, immunocompetent adults aged 65 to 94 from 2000 to 2003. Presumptive pneumonia cases were identified from health plan automated data and validated through medical record review. Two controls were selected for each case with pneumonia, matched on age, sex, and calendar year. MEASUREMENTS: Information about opioid and benzodiazepine use came from computerized pharmacy data. Information on covariates including comorbid illnesses and functional and cognitive status came from medical record review and electronic health data. RESULTS: One thousand thirty-nine validated cases of pneumonia and 2,022 matched controls were identified. One hundred forty-four (13.9%) cases and 161 (8.0%) controls used prescription opioids (adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08-1.76 vs nonuse). Risk was highest for opioids categorized as immunosuppressive based on immunological studies (OR = 1.88, 95% CI = 1.26-1.79 vs nonuse), whereas for nonimmunosuppressive opioids the OR was 1.23 (95% CI = 0.89-1.69). Risk was highest in the first 14 days of use (OR = 3.24, 95% CI = 1.64-6.39 vs nonuse). For long-acting opioids, the OR was 3.43 (95% CI = 1.44-8.21) versus nonuse, whereas for short-acting opioids, it was 1.27 (95% CI = 0.98-1.64). No greater risk was seen for current benzodiazepine use compared to nonuse (OR = 1.08, 95% CI = 0.80-1.47). CONCLUSION: Use of opioids but not benzodiazepines was associated with pneumonia risk. The differences in risk seen for different opioid regimens warrant further study. PMID- 22091504 TI - Cognitive complaints, depressive symptoms, and cognitive impairment: are they related? AB - OBJECTIVES: To examine whether concurrent depressive symptoms and self- and informant-reported cognitive impairments are related to cognitive complaints. DESIGN: Longitudinal aging study of the relationship between depressive symptoms, reported cognitive impairments, and cognitive complaints. Mixed-effects regression models were used to determine whether scores on the Center for Epidemiologic Studies Depression Scale (CES-D) and Clinical Dementia Rating Scale (CDR) predicted cognitive complaints. The Cognitive Failures Questionnaire (CFQ) assessed cognitive complaints. SETTING: A community-dwelling sample in Baltimore, Maryland. PARTICIPANTS: One hundred five cognitively normal older individuals with a mean baseline age of 75 followed for an average of 4 years. MEASUREMENTS: The CES-D measured depressive symptoms. The CDR Sum of Boxes (CDR-SB) measured self- and informant-reported impairment, and the CFQ measured cognitive complaints. RESULTS: Greater depressive symptoms and reported impairments are associated with higher CFQ scores. In addition, there was a significant interaction between depressive symptoms and reported impairment. Specifically, individuals without reported cognitive impairment had the strongest association between depressive symptoms and cognitive complaints. Finally, reported impairments interact with baseline age, suggesting that the relationship between reported impairments and cognitive complaints is strongest in individuals younger than 80. CONCLUSION: These findings confirm a relationship between reported cognitive impairment and cognitive complaints in older individuals and highlight the extent to which age and depressive symptoms account for variation in complaints. These factors should be considered when interpreting cognitive complaints in a clinical setting. PMID- 22091505 TI - Chronic physical conditions in older adults with mental illness and/ or substance use disorders. AB - OBJECTIVES: To examine the association between mental illness and chronic physical conditions in older adults and investigate whether co-occurring substance use disorders (SUDs) are associated with greater risk of chronic physical conditions beyond mental illness alone. DESIGN: A retrospective cross sectional study. SETTING: Medicare and Medicaid programs in Massachusetts. PARTICIPANTS: Massachusetts Medicare and Medicaid members aged 65 and older as of January 1, 2005 (N = 679,182). MEASUREMENTS: Diagnoses recorded on Medicare and Medicaid claims were used to identify mental illness, SUDs, and 15 selected chronic physical conditions. RESULTS: Community-dwelling older adults with mental illness or SUDs had higher adjusted risk for 14 of the 15 selected chronic physical conditions than those without these disorders; the only exception was eye diseases. Moreover, those with co-occurring SUDs and mental illness had the highest adjusted risk for 11 of these chronic conditions. For residents of long term care facilities, mental illness and SUDs were only moderately associated with the risk of chronic physical conditions. CONCLUSION: Community-dwelling older adults with mental illness or SUDs, particularly when they co-occurred, had substantially greater medical comorbidity than those without these disorders. For residents of long-term care facilities, the generally uniformly high medical comorbidity may have moderated this relationship, although their high prevalence of mental illness and SUDs signified greater healthcare needs. These findings strongly suggest the imminent need for integrating general medical care, mental health services, and addiction health services for older adults with mental illness or SUDs. PMID- 22091506 TI - The cholesterol conundrum. PMID- 22091507 TI - Do vitamin D levels influence the risk of diabetes mellitus and play a role in healthier aging? PMID- 22091508 TI - Handing down memories of Jesse Owens. PMID- 22091509 TI - Unilateral acute pyelonephritis associated with a neglected pessary. PMID- 22091510 TI - Common but critical sensation in older adults. PMID- 22091511 TI - A false diabetic foot ulcer. PMID- 22091512 TI - An uncommon cause of upper gastrointestinal bleeding, blister pack drug. PMID- 22091513 TI - Prevention of chronic obstructive pulmonary disease exacerbation by angiotensin converting enzyme inhibitors in individuals with impaired swallowing. PMID- 22091514 TI - Shelter-acquired pneumonia after a catastrophic earthquake in Japan. PMID- 22091515 TI - Population-based smoking trends in older adults: the Minnesota Heart Survey. PMID- 22091516 TI - Strong association between polycythemia and glucose intolerance in older adults living at high altitudes in the Andes. PMID- 22091517 TI - Association between high variability of gait speed and mild cognitive impairment: a cross-sectional pilot study. PMID- 22091518 TI - Improving office detection of asymptomatic dementia. PMID- 22091519 TI - Structured history taking of medication use reveals iatrogenic harm due to discrepancies in medication histories in hospital and pharmacy records. PMID- 22091520 TI - Is frailty associated with cardiovascular drug use? PMID- 22091521 TI - Telomere length in old age and cholesterol across the life course. PMID- 22091522 TI - Defining palliative care competencies in Canadian geriatric medicine subspecialty training. PMID- 22091523 TI - End-of-life and formal and informal care use of community-dwelling older adults with different levels of physical disability. PMID- 22091524 TI - Social support and mortality: if you're sick, friends can't save you. PMID- 22091525 TI - Elderly: a term to avoid or to embrace? PMID- 22091526 TI - The aging paradox: how old is old and all that jazz? PMID- 22091527 TI - Cholinesterase inhibitor initiation in hospital setting. PMID- 22091528 TI - Individualized nutritional intervention during and after hospitalization: the nutrition intervention study clinical trial. PMID- 22091530 TI - Noncovalently functionalized multiwalled carbon nanotubes by chitosan-grafted reduced graphene oxide and their synergistic reinforcing effects in chitosan films. AB - Water-soluble chitosan-grafted reduced graphene oxide (CS-rGO) sheets are successfully synthesized via amidation reaction and chemical reduction. CS-rGO possesses not only remarkable graphitic property but also favorable water solubility, which is found to be able to effectively disperse multiwalled carbon nanotubes (MWCNTs) in acidic solutions via noncovalent interaction. The efficiency of CS-rGO in dispersing MWCNTs is tested to be higher than that of plain graphene oxide (GO) and a commercial surfactant, sodium dodecyl sulfate (SDS). With incorporation of 1 wt % CS-rGO dispersed MWCNTs (CS-rGO-MWCNTs), the tensile modulus, strength and toughness of the chitosan (CS) nanocomposites can be increased by 49, 114, and 193%, respectively. The reinforcing and toughening effects of CS-rGO-MWCNTs are much more prominent than those of single-component fillers, such as MWCNTs, GO, and CS-rGO. Noncovalent pi-pi interactions between graphene sheets and nanotubes and hydrogen bonds between grafted CS and the CS matrix are responsible for generating effective load transfer between CS-rGO MWCNTs and the CS matrix, causing the simultaneously increased strength and toughness of the nanocomposites. PMID- 22091531 TI - Fluoride as a probe for H-bonding interactions in the active site of heme proteins: the case of Thermobifida fusca hemoglobin. AB - The structural and functional properties of the active site of the bacterial hemoglobin from Thermobifida fusca are largely determined by three polar amino acids: TrpG8, TyrCD1, and TyrB10. We have exploited the availability of a combinatorial set of mutants, in each of which these three amino acids have been singly, doubly, or triply replaced by a Phe residue, to perform a detailed study on H-bonding interactions between the protein and heme-bound fluoride. By appropriate choice of the excitation conditions, nu(Fe-F) stretching bands have been detected in the resonance Raman spectra. In the wild-type protein and one of the mutants, two nu(Fe-F) bands have been observed and assigned to the presence of two protein conformers where fluoride is singly or doubly H-bonded. Furthermore, by plotting the CT1 charge-transfer transition energy vs the nu(Fe F) wavenumbers, an empirical correlation has been found. The data are well fitted by a straight line with a positive slope. The position along the correlation line can be considered as a novel, general spectroscopic indicator of the extent of H bonding in the active site of heme proteins. In agreement with the spectroscopic results, we have observed that the rate of ligand dissociation in stopped-flow kinetic measurements progressively increases upon substitution of the H-bonding amino acids. Molecular dynamics simulations have been performed on the fluoride complexes of native and mutated forms, indicating the prevalent interactions at the active site. All the techniques yield evidence that TrpG8 and TyrCD1 can form strong H bonds with fluoride, whereas TyrB10 plays only a minor role in the stabilization of the ligand. PMID- 22091532 TI - Ribose 5-phosphate glycation reduces cytochrome c respiratory activity and membrane affinity. AB - Spontaneous glycation of bovine heart cytochrome c (cyt c) by the sugar ribose 5 phosphate (R5P) weakens the ability of the heme protein to transfer electrons in the respiratory pathway and to bind to membranes. Trypsin fragmentation studies suggest the preferential sites of glycation include Lys72 and Lys87/88 of a cationic patch involved in the association of the protein with its respiratory chain partners and with cardiolipin-containing membranes. Reaction of bovine cyt c with R5P (50 mM) for 8 h modified the protein in a manner that weakened its ability to transfer electrons to cytochrome oxidase by 60%. An 18 h treatment with R5P decreased bovine cyt c's binding affinity with cardiolipin-containing liposomes by an estimated 8-fold. A similar weaker binding of glycated cyt c was observed with mitoplasts. The reversal of the effects of R5P on membrane binding by ATP further supports an A-site modification. A significant decrease in the rate of spin state change for ferro-cyt c, thought to be due to cardiolipin insertion disrupting the coordination of Met to heme, was found for the R5P treated cyt c. This change occurred to a greater extent than what can be explained by the permanent attachment of the protein to the liposome. Turbidity changes resulting from the multilamellar liposome fusion that is readily promoted by cyt c binding were not seen for the R5P-glycated cyt c samples. Collectively, these results demonstrate the negative impact that R5P glycation can have on critical electron transfer and membrane association functions of cyt c. PMID- 22091533 TI - Functional neural correlates of psychometric schizotypy: an fMRI study of antisaccades. AB - Dimensional models of psychosis assume a continuum between schizotypy and schizophrenia. However, little is known about the overlap in brain functional alterations between schizotypy and schizophrenia. Fifty-four healthy volunteers underwent functional magnetic resonance imaging during an antisaccade task, a measure of cognitive control known to be impaired in schizophrenia, and a prosaccade task. Higher positive schizotypy was correlated with higher antisaccade error rates. Associations between reduced blood oxygenation level dependent signal and higher schizotypy were found during antisaccades in the putamen, thalamus, cerebellum, and visual cortex and during prosaccades in the visual cortex, supplementary eye field, and posterior intraparietal sulcus. These findings show that increased schizotypy is associated with decreased antisaccade performance and reduced brain function in regions also affected in schizophrenia, therefore providing evidence of neurocognitive and neurophysiological overlap between schizotypy and schizophrenia. PMID- 22091534 TI - A randomized study of aspiration and sclerotherapy versus laparoscopic deroofing in management of symptomatic simple renal cysts. AB - PURPOSE: To perform a prospective randomized study to evaluate aspiration and sclerotherapy vs. laparoscopic deroofing in the management of symptomatic simple renal cysts. PATIENTS AND METHODS: Forty patients with symptomatic simple renal cysts were randomized to treatment either by ultrasonography-guided aspiration and sclerotherapy (group A-20 patients) or by laparoscopic deroofing (group B-20 patients). Two patients in group A and one patient in group B had a parapelvic cyst. Patients were evaluated by urine analysis, serum creatinine level, coagulation profile, ultrasonography, and CT urography. In group A patients, after aspiration, 1% polidocanol in a volume equivalent to 10% of cyst volume was instilled. In group B patients, laparoscopic deroofing was performed. All patients were followed up by ultrasonography up to 1 year after treatment. RESULTS: In group A, aspiration and sclerotherapy was performed on an outpatient basis, and none of the patients needed postoperative analgesia. Eighteen of 20 patients had complete regression; two of these had parapelvic cyst. Partial regression with relief of pain was noted in one patient, whereas treatment failed in one patient. None of the patients had any significant complication and none required analgesia. All the patients were discharged two hours after the procedure. In group B, laparoscopic deroofing was successfully performed in 19 of 20 patients. Laparoscopic deroofing could not be performed in one patient with parapelvic cyst because of failure of access. The mean analgesic requirement was 285 +/- 57.98 (200-400) mg tramadol, and average hospital stay was 2.1 +/- 0.32 (2-3) days. CONCLUSION: Percutaneous aspiration and sclerotherapy with polidocanol is an effective, safe, and minimally invasive therapeutic option for symptomatic simple renal cysts, with equal efficacy and lower morbidity and hospital stay in comparison with laparoscopic deroofing. PMID- 22091535 TI - Cognitive functioning predicts driver safety on road tests 1 and 2 years later. AB - OBJECTIVES: To describe longitudinal changes in mean level and evaluate rank order stability in potential predictors of driving safety (visual sensory, motor, visual attention, and cognitive functioning) and safety errors during an 18-mile on-road driving test in older adults and to evaluate the relative predictive power of earlier visual sensory, motor, visual attention, and cognitive functioning on future safety errors, controlling for earlier driving capacity. DESIGN: Three-year longitudinal observational study. SETTING: Large teaching hospital in the Midwest. PARTICIPANTS: One hundred eleven neurologically normal older adults (60-89 at baseline). MEASUREMENTS: Safety errors based on video review of a standard 18-mile on-road driving test served as the outcome measure. A comprehensive battery of tests on the predictor side included visual sensory functioning, motor functioning, cognitive functioning, and a measure of useful field of view. RESULTS: Longitudinal changes in mean levels of safety errors and cognitive functioning were small from year to year. Relative rank-order stability between consecutive assessments was moderate in overall safety errors and moderate to strong in visual attention and cognitive functioning. Although prospective bivariate correlations between safety errors and predictors ranged from fair to moderate, only functioning in the cognitive domain predicted future driver performance 1 and 2 years later in multivariate analyses. CONCLUSION: Normative aging-related declines in driver performance as assessed using on-road tests emerge slowly. Even in the presence of conservative controls, such as previous driving ability, age, and visual sensory and motor functioning, cognitive functioning predicted future on-road driving performance 1 and 2 years later. PMID- 22091536 TI - Persistent enhancement of functional MRI responsiveness to sensory stimulation following repeated seizures. AB - PURPOSE: Neural reorganization and interictal behavioral anomalies have been documented in people with epilepsy and in animal seizure models. Alterations in behavior could be due to somatosensory dysfunction. This study was designed to determine whether seizures can lead to changes in somatosensory representations and whether those changes are persistent. METHODS: Twice-daily seizures were elicited by delivering 1 s of electrical stimulation through carbon fiber electrodes implanted in both the corpus callosum and sensorimotor neocortex of young adult male Long-Evans rats until a total of 20 seizures were elicited. Either 1-3 days or 3-5 weeks following the last seizure, functional magnetic resonance imaging (MRI) was used to image the brain during electrical stimulation of each forepaw independently. KEY FINDINGS: Forepaw stimulation in control rats resulted in a focused and contralateral fMRI signal in the somatosensory neocortex. Rats that had repeated seizures had a 151% increase in the number of voxels activated in the contralateral hemisphere 1-3 days after the last seizure and a 166% increase at 3-5 weeks after the last seizure. The number of voxels activated in response to forepaw stimulation was positively correlated with the duration of the longest seizure experienced by each rat. The intensity of the activated voxels was not significantly increased at either time interval from the last seizure. SIGNIFICANCE: The increased area of activation in somatosensory cortex, which is persistent at 3-5 weeks, is consistent with previous observations of larger motor maps following seizures. Seizure-induced changes in the functioning of sensory cortex may also contribute to interictal behavioral anomalies. PMID- 22091537 TI - Development of neutralizing antibody responses in muskellunge, Esox masquinongy (Mitchill), experimentally exposed to viral haemorrhagic septicaemia virus (genotype IVb). AB - A complement-dependent 50% plaque neutralization test was used to assess the neutralizing antibody response in sera of muskellunge, Esox masquinongy, experimentally infected with viral haemorrhagic septicaemia virus (VHSV, genotype IVb) by immersion. Groups of muskellunge were challenged with varying concentrations of VHSV: Group 1 with 10(2) plaque-forming units (pfu) mL(-1) , Group 2 with 4 * 10(3) pfu mL(-1) , Group 3 with 10(5) pfu mL(-1) and Group 4 with 0 pfu mL(-1) . The fish were held at a temperature of 11 +/- 1 degrees C and were sampled over a 20-week period. Neutralizing antibodies were not detected in sera of any of the negative control fish throughout the study. Low neutralizing titres were detected in Groups 1-3 by 6 days post-infection (p.i.). Neutralizing titres of >=80 [corrected]. were not detected again until 3, 4 and 7 weeks p.i. for Groups 2, 3 and 1, respectively, with peak titres for those groups occurring 16, 11 and 17 weeks p.i., respectively. VHSV was detected in serum for up to 11 weeks p.i. Results of this study show that survivors can be detected by a serological technique, despite being virus negative. This may benefit the investigation of VHSV IVb distribution in the Great Lakes and the study of host immune responses to this emerging sublineage. PMID- 22091538 TI - Microalgae in the postgenomic era: a blooming reservoir for new natural products. AB - Bacteria, fungi, algae and higher plants are the most prolific producers of natural products (secondary metabolites). Compared to macroalgae, considerably fewer natural products have been isolated from microalgae, which offer the possibility of obtaining sufficient and well-defined biological material from laboratory cultures. Interest in microalgae is reinforced by large-scale data sets from genome sequencing projects and the development of genetic tools such as transformation protocols. This review highlights what is currently known about the biosynthesis and biological role of natural products in microalgae, with examples from isoprenoids, complex polyketides, nonribosomal peptides, polyunsaturated fatty acids and oxylipins, alkaloids, and aromatic secondary metabolites. In addition, we introduce a bioinformatic analysis of available genome sequences from totally 16 microalgae, belonging to the green and red algae, heterokonts and haptophytes. The results suggest that the biosynthetic potential of microalgae is underestimated and many microalgal natural products remain to be discovered. PMID- 22091539 TI - Income and reproductive motivation. AB - Abstract It is often assumed that family size and income would be positively related if unwanted births among the less advantaged were prevented. But this assumption rests on a prior expectation that family-size preferences bear a direct relation to income in modern societies. Data on such reproductive preferences in relation to economic status from 13 studies in the United States dating between 1936 and 1966 do not support the notion of a positive association between reproductive preferences and income. Only when Catholics are considered is there even a U-shaped relation between family-size desires and income. These results cast doubt on the notion that the economic theory of demand for consumer durables is relevant to reproductive motivation. Rather, the data lend credence to the idea that significant non-economic influences associated with prosperity depress family-size desires among the well-to-do. Only if these influences are specifically weakened by a counter-force (such as Catholicism) do wealthier people show a preference for somewhat larger families. In no case, however, are the Catholic/non-Catholic differences in reproductive preference large. Moreover, no economic group, even among non-Catholics, prefers very small families. PMID- 22091540 TI - Malaria eradication and its effect on mortality levels. AB - Abstract It is argued in this article that malaria eradication was only one of a group of factors which were responsible for the lowering of mortality levels in Ceylon in the years after 1946. The magnitude of the contribution made by these other factors has not generally been taken into account since they took effect during the period of malaria eradication, but since some of them were carried out in a few of the endemic malarial areas during the pre-eradication period, some attempt to measure them can be made of their impact on mortality levels. Further the effect of malaria eradication on mortality levels in the absence of these other measures is also studied by examining the case of Guatemala where in spite of malaria eradication the decline in mortality levels has not been so significant as in Ceylon. PMID- 22091541 TI - The interaction of demand and supply and its effect on the female labour force in the United States. AB - Abstract In both 1900 and 1940 young women and unmarried women formed the most important component of the female labour force. By 1960, however, older women and married women had replaced them. An explanation for this shift is sought in divergent trends in the demand for female labour and in the supply of the kind of female workers typical of the 1900-40 period. Three series of estimates of the demand for female labour are compared to six series of estimates of the supply of different types of women. It was found that all three series of estimates of demand showed a rising demand for female workers in the 1900 to 1960 period. However, the number of young women (those aged 18-34) and of unmarried women, aged 18-64 was actually declining in the 1940 to 1960 period. As a consequence, the supply of such women was well below our estimates of demand in 1960. The maintenance and continued expansion of the female labour force in the 1940 to 1960 period rested, therefore, on the greater utilization of married women and women over the age of 35. As a consequence, the age and marital-status composition of the female labour force has undergone considerable changes in the 1940 to 1960 period. PMID- 22091542 TI - Population and social structure in a Bedfordshire parish: The Cardington listing of inhabitants, 1782. AB - Abstract This paper describes some of the main social and demographic characteristics of a Bedfordshire parish in the second half of the eighteenth century. It is based on an analysis of the 'Listing of Inhabitants' of Cardington in 1782, and on the use of the parish registers. The listing does not allow an analysis of the entire population of the parish. Its most serious deficiency is the failure to give sufficient detail for the upper social strata of the parish population, viz. the residents of 'farm tenements' and a small number of other properties likewise poorly documented. In the main, the data given in the article refer only to the residents of 'cottage tenements'. They represent the majority of the parish population, but omit the small group at the top of village society. For the 'cottage tenement' population a number of conclusions are drawn. Within this population there was an overall excess of females over males, but the excess was slight, and the number and proportion of males and females in each age-group balanced quite closely. 43-44% of the population of known age were less than 15 years old, and almost half the population were aged between 16 and 60 years. An analysis of marital status tentatively suggests that adult celibacy was rare. The average number of residents per 'cottage' household was only a little higher than the average size of family, confirming that only a small proportion of households contained more than one family. Household and family size may have been larger among craftsmen than labourers, with the households and families of the former containing more resident offspring than those of the latter. About one in every three marriages was either a broken marriage or are-marriage. A reconstitution of certain 'cottage tenement' families tentatively suggests an average of over five baptisms per family. Yet there were only two resident offspring per family in 1782. The difference may be explained by the high level of infant and child mortality, with one-third of all baptised children failing to reach the age of 15 years, and by the high degree of population mobility, albeit over short distances. PMID- 22091543 TI - Some factors associated with Urban-Rural fertility differentials in Mexico. AB - Abstract Warren C. Robinson and others have presented strong evidence that a substantial portion of the variation in urban-rural fertility differentials is attributable to variations in infant and child mortality when the child-woman ratio is the index of fertility. This paper focuses on the contributions of several additional factors in accounting for variations in urban-rural fertility differentials. 1960 census data for 23 urban and rural areas in Mexico are investigated by means of correlation analysis. City growth and literacy differentials are found to be significantly related to the size of the urban rural fertility (child-woman ratio) differential, but their effect appears to be indirect, and brought about by their association with urban-rural differentials in the sex ratio at the reproductive ages, age at marriage, and the percentage married. The latter three factors are positively related to the size of the urban rural fertility differential. City growth is inversely related to the magnitude of the fertility differential. This analysis suggests that changes in (urban) population composition may favour higher as well as lower urban fertility and thus affect the size of the urban-rural fertility differential. If this is true, it would appear that urbanization does not necessarily lead to lower total fertility (at least in its early stages), but may lead to the modification of certain demographic characteristics which formerly favoured lower urban fertility. The long-run effects of urbanization are more difficult to assess, but it is suggested that migrants to urban areas may require several generations to manifest lower fertility. This would constitute an additional factor favouring higher urban fertility. The possible contribution of changing mortality conditions is also considered. PMID- 22091545 TI - Notes. PMID- 22091547 TI - Assessment of the mutagenicity of aromatic amines from theoretical structural parameters: a hierarchical approach. AB - Abstract A hierarchical approach has been used in this paper in predicting the mutagenicity/non-mutagenicity of a set of 127 chemicals from their molecular descriptors. The set of descriptors consisted of topostructural and topochemical parameters, experimental properties like log P, and quantum chemical indices calculated using a semi-empirical method. The results show that a combination of topostructural and topochemical molecular descriptors explain most of the variance in the experimental data. The addition of physical properties or quantum chemical parameters did not make any significant improvement in the predictive power of the models. PMID- 22091548 TI - Chemical sub-structural cluster expansions for molecular properties. AB - Abstract The correlation of different molecular sub-structures with various molecular properties has a long history, of over a century. And currently such structural characterizations still remain of central interest in chemistry. Thus a general formalism to analyze a property or activity in terms of sub-structural contributions is of interest, and is pursued here. The approach may indeed be viewed as a formalization and extension of standard bond-energy ideas as arise even in introductory chemistry courses. The present formalism allows for: * a more complete and comprehensive formulation, with higher-order corrections to achieve greater accuracy; * a more general form for the class of sub-structures appearing in the expansion, thereby allowing more general (e.g., "multiplicative") properties to be expanded; and * a more general form for the expansion functions, thereby allowing more rapid convergence rates for the expansions. An illustrative example for the structure/property correlation of conjugated-hydrocarbon pi-energy is made. Some comments on the use for describing bio-activities, and in particular toxicities, are made. PMID- 22091549 TI - A novel electron-conformational approach to molecular modeling for QSAR by identification of pharmacophore and anti-pharmacophore shielding. AB - Abstract A novel method of pharmacophore identification and activity prediction in structure-activity (structure-property) relationships is worked out as an essential extension and improvement of previous publications. In this method each conformation of the molecular systems in the training set of the SAR problem is presented by both electronic structure and geometry parameters arranged in a matrix form. Multiple comparisons of these matrices for the active and inactive compounds allows one to separate a smaller number of matrix elements that are common for all the active compounds and are not present in the same arrangement in the inactive ones. This submatrix of activity represents the pharmacophore (Pha). By introducing the Anti-Pharmacophore Shielding (APS) defined as molecular groups and competing charges outside the Pha that hinder the proper docking of the Pha with the bioreceptor, the procedure of Pha identification is essentially reduced to the treatment of a smaller number of simplest in structure most active and inactive compounds. A simple empirical scheme is suggested to estimate the APS numerically, while the contributions of different conformations of the same compound are taken into account by means of Boltzmann distribution. This enables us to make approximate quantitative predictions of activities. In application to rice blast activity we reached an approximately 100% (within experimental error) prediction probability of the activity qualitatively (yes, no), and with r (2) = 70% quantitatively. PMID- 22091550 TI - Calculation of octanol/water partition coefficients for pesticides: a comparative study. AB - Abstract On the basis of a set of 593 experimental octanol/water partition coefficients (log P) for pesticides, the simulation performances of two models using computable descriptors are compared. The back propagation neural network model designed from autocorrelation descriptors (SAR QSAR Environ. Res. (1997), 7, 151-172) compares favorably with the AFC model (J. Pharm. Sci. (1995), 84, 83 92) using atom/fragment contributions and correction factors. PMID- 22091551 TI - Editorial board page for "SAR and QSAR in Environmental Research", Volume 10, Number 2-3. AB - Abstract This is a scanned image of the original Editorial Board page(s) for this issue. PMID- 22091552 TI - Preface. PMID- 22091553 TI - Sequential Stevens-Johnson syndrome and photo-recall phenomenon. PMID- 22091554 TI - Increasing the number of irrelevant stimuli increases ability to detect countermeasures to the P300-based Complex Trial Protocol for concealed information detection. AB - We previously found that simultaneously executing a mental countermeasure and an explicit required response impairs reaction time (RT)-based detection of countermeasure use in a P300- based concealed information test. To address this issue, we increased the numbers of irrelevant stimuli to eight, and manipulated the proportions of to-be-countered irrelevant stimuli from 25% to 50% to 75% in three groups. RESULTS: Based on P300 data, 100% of the simple guilty (no countermeasure use) and 92% of the innocent subjects were correctly identified as having or not having concealed information. In the countermeasure groups, detection rates varied from 71% to 92% across the different groups. Notably, in the present study with eight irrelevant items, simultaneous countermeasure use was indicated by elevated RT in the 50% and 75% countermeasure proportion groups, which it was not, previously, with 50% (two) countermeasures and four irrelevants. PMID- 22091555 TI - Potential limitations in the use of KillerRed for fluorescence microscopy. AB - KillerRed, a bright red fluorescent protein, is a genetically encoded photosensitizer, which generates radicals and hydrogen peroxide upon green light illumination. The protein is a potentially powerful tool for selective light induced protein inactivation and cell killing, and can also be used to study downstream effects of locally increased levels of reactive oxygen species. The initial aim of this study was to investigate whether or not KillerRed-mediated reactive oxygen species production inside peroxisomes could trigger the sequestration of these organelles into autophagosomes. Green fluorescent protein tagged microtubule-associated protein 1 light chain 3 was used as autophagosome marker. We observed that KillerRed also emits weak green fluorescence upon excitation at 480 nm, and this may lead to erroneous data interpretation in conditions where green fluorophores are used. We discuss this potential pitfall of KillerRed for biological imaging and formulate recommendations to avoid misinterpretation of the data. PMID- 22091556 TI - Keeping it simple: flowering plants tend to retain, and revert to, simple leaves. AB - * A wide range of factors (developmental, physiological, ecological) with unpredictable interactions control variation in leaf form. Here, we examined the distribution of leaf morphologies (simple and complex forms) across angiosperms in a phylogenetic context to detect patterns in the directions of changes in leaf shape. * Seven datasets (diverse angiosperms and six nested clades, Sapindales, Apiales, Papaveraceae, Fabaceae, Lepidium, Solanum) were analysed using maximum likelihood and parsimony methods to estimate asymmetries in rates of change among character states. * Simple leaves are most frequent among angiosperm lineages today, were inferred to be ancestral in angiosperms and tended to be retained in evolution (stasis). Complex leaves slowly originated ('gains') and quickly reverted to simple leaves ('losses') multiple times, with a significantly greater rate of losses than gains. Lobed leaves may be a labile intermediate step between different forms. The nested clades showed mixed trends; Solanum, like the angiosperms in general, had higher rates of losses than gains, but the other clades had higher rates of gains than losses. * The angiosperm-wide pattern could be taken as a null model to test leaf evolution patterns in particular clades, in which patterns of variation suggest clade-specific processes that have yet to be investigated fully. PMID- 22091557 TI - A novel injectable in situ forming poly-DL-lactide and DL-lactide/glycolide implant containing lipospheres for controlled drug delivery. AB - One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 1-24 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96 Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl 2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40 mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI. PMID- 22091558 TI - Pre-operative and intraoperative determinants for prolonged ventilation following adult cardiac surgery. AB - BACKGROUND: Prolonged ventilation is a serious complication after cardiac surgery, but few risk prediction models exist. Our objectives were to develop a specific risk prediction model based on pre-operative variables, to identify whether selected intraoperative variables could improve prediction, and to compare our model with the EuroSCORE. METHODS: Data from 5027 patients undergoing open-heart surgery in 2000-2007 were used for logistic regression model development. Internal validation was performed by bootstrapping. Discrimination and calibration were assessed with areas under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow test. Our pre-operative model was compared with predictions based on the additive and logistic EuroSCORE. RESULTS: Age, previous cardiac surgery, peripheral arterial disease, left ventricular hypertrophy, chronic pulmonary disease, renal insufficiency, pre operative hemoglobin concentration, urgent or emergency operation, and operation other than isolated coronary artery bypass grafting were identified as pre operative predictors for prolonged ventilation (model I). Discrimination and accuracy were excellent (AUC: 0.848 and shrinkage factor: 94%). Calibration was good (Hosmer-Lemeshow test: P = 0.43). Inclusion of a few intraoperative variables somewhat improved the model, increasing shrinkage factors (96%) and discrimination ability (AUC model II = 0.870 and model III = 0.875 for two alternative such models). Our pre-operative model showed better performance than the logistic or additive EuroSCORE. CONCLUSIONS: The pre-operative risk prediction model for prolonged ventilation with easily obtainable variables in routine clinical work performed well and was only slightly improved by inclusion of intraoperative variables. Performance was better than with the EuroSCORE. PMID- 22091559 TI - Physician practices and readiness for medical home reforms: policy, pitfalls, and possibilities. AB - OBJECTIVE: To determine the proportion of physician practices in the United States that currently meets medical home criteria. DATA SOURCE/STUDY SETTING: 2007 and 2008 National Ambulatory Medical Care Survey. STUDY DESIGN: We mapped survey items to the National Committee on Quality Assurance's (NCQA's) medical home standards. After awarding points for each "passed" element, we calculated a practice's infrastructure score, dividing its cumulative total by the number of available points. We identified practices that would be recognized as a medical home (Level 1 [25-49 percent], Level 2 [50-74 percent], or Level 3 [infrastructure score >=75 percent]) and examined characteristics associated with NCQA recognition. RESULTS: Forty-six percent (95 percent confidence interval [CI], 42.5-50.2) of all practices lack sufficient medical home infrastructure. While 72.3 percent (95 percent CI, 64.0-80.7 percent) of multi-specialty groups would achieve recognition, only 49.8 percent (95 percent CI, 45.2-54.5 percent) of solo/partnership practices meet NCQA standards. Although better prepared than specialists, 40 percent of primary care practices would not qualify as a medical home under present criteria. CONCLUSION: Almost half of all practices fail to meet NCQA standards for medical home recognition. PMID- 22091560 TI - Passion for a cause, passion for a creed: on ideological passion, identity threat, and extremism. AB - Passion energizes and directs both peaceful and violent ideologically inspired movements. The type of ideological passion that underlies people's political or religious commitment was proposed to moderate the effect of social identity threatening circumstances on their choice of activist tactics. Ideological passion was defined as a strong inclination toward a loved, valued, and self defining cause, ideology, or group in which people invest considerable time and energy. Harmonious ideological passion was expected to promote peaceful activism and nonviolence partly because it is anchored in a strong and secure sense of identity-one that facilitates nondefensiveness in identity-threatening circumstances. Obsessive ideological passion, in contrast, was expected to engender hatred and aggressive extremism in identity-threatening circumstances partly because it is anchored in a strong, but insecure, sense of identity. Results from 2 studies, conducted with nationalist activists (N = 114) and devout Muslims (N = 111), supported these hypotheses. Implications for the motivation/passion and intergroup literatures are discussed. PMID- 22091561 TI - Relationship between patient safety and hospital surgical volume. AB - OBJECTIVE: To examine the relationship between hospital volume and in-hospital adverse events. DATA SOURCES: Patient safety indicator (PSI) was used to identify hospital-acquired adverse events in the Nationwide Inpatient Sample database in abdominal aortic aneurysm, coronary artery bypass graft, and Roux-en-Y gastric bypass from 2005 to 2008. STUDY DESIGN: In this observational study, volume thresholds were defined by mean year-specific terciles. PSI risk-adjusted rates were analyzed by volume tercile for each procedure. PRINCIPAL FINDINGS: Overall, hospital volume was inversely related to preventable adverse events. High-volume hospitals had significantly lower risk-adjusted PSI rates compared to lower volume hospitals (p < .05). CONCLUSION: These data support the relationship between hospital volume and quality health care delivery in select surgical cases. This study highlights differences between hospital volume and risk adjusted PSI rates for three common surgical procedures and highlights areas of focus for future studies to identify pathways to reduce hospital-acquired events. PMID- 22091562 TI - Conservative versus arthroscopic management for medial coronoid process disease in dogs: a prospective gait evaluation. AB - OBJECTIVE: To investigate, using objective gait analysis, the long-term outcome of dogs with medial coronoid process disease (MCPD) treated with conservative management (CM) versus arthroscopic treatment (AT). STUDY DESIGN: Prospective clinical trial. ANIMALS: Dogs (n = 20) with unilaterally confirmed MCPD. METHODS: Eleven dogs were treated arthroscopically with removal of coronoid fragments and burring of any associated chondromalacic cartridge and 9 dogs were managed conservatively. All dogs were administered a 6-week course of oral tepoxalin on enrollment. Inverse dynamics gait analysis was performed at initial presentation and at 4, 8, 26, and 52 weeks. The gait variables analyzed were elbow moment (EM), elbow power (EP), total support moment (TSM), and total support moment ratio (TSMR) as a measure of forelimb asymmetry. RESULTS: Affected peak EM increased from 0.58 to 0.76 Nm/kg in the AT dogs, and from 0.66 to 0.81 Nm/kg in the CM dogs and there was no significant difference between groups. Affected peak EP increased marginally in the AT dogs, but was unchanged in the CM dogs and there was no significant difference between groups. TSM increased from 1.49 to 1.92 Nm/kg in the AT dogs and from 1.52 to 2.06 Nm/kg in the CM dogs and there was no significant difference between groups. TSMR was statistically different between treatment groups at 1 (P = .003) and 2 months (P = .048) with the AT group more asymmetric and hence more lame. TSMR at 12 months was 0.83 (AT) and 0.86 (CM) implying a failure of return to soundness by either group. CONCLUSIONS: AT dogs had increased mechanical asymmetry at 4 and 8 weeks compared to the CM group revealing surgery worsened limb function. There was no significant difference in mechanical symmetry between groups at 26 and 52 weeks. PMID- 22091563 TI - Once-yearly zoledronic acid in older men compared with women with recent hip fracture. AB - OBJECTIVES: To assess the efficacy of once-yearly zoledronic acid (ZOL) 5 mg in increasing bone mineral density (BMD) in men with a recent hip fracture participating in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once- Yearly Recurrent Fracture Trial and to compare the efficacy with that in women from the same study. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: International multicenter. PARTICIPANTS: Five hundred and eight men and 1,619 women within 90 days of surgical repair of low-trauma hip fracture in the same study (for comparison). INTERVENTION: Once-yearly intravenous (IV) ZOL 5 mg (n = 248) or placebo (n = 260), loading dose of vitamin D, daily calcium, and vitamin D supplements. MEASUREMENT: Changes in BMD. RESULTS: Percentage change from baseline in total hip BMD at Months 12 and 24 was significantly higher with ZOL than with placebo (between-group difference, 2.0%, P = .003, and 3.8%, P = .002, respectively). Percentage change from baseline in femoral neck BMD at Month 24 was significantly higher with ZOL than with placebo (3.8%, P = .003). The BMD benefit was comparable with that observed in women in this study. New clinical fractures occurred in 36 (7.1%) participants (ZOL, n = 16; placebo, n = 20; P = .64). The ZOL safety profile was comparable with that of placebo, with no significant differences in cardiovascular or long-term renal function and a trend toward lower mortality in ZOL-treated men. CONCLUSION: Once yearly IV ZOL 5 mg increases bone mass at the hip and femoral neck in men within 90 days of repair of a low-trauma hip fracture. Increases were of a similar magnitude to those observed in women in the same study. PMID- 22091564 TI - Building a delirium network. PMID- 22091565 TI - E Pluribus Unum. PMID- 22091566 TI - Delirium: a strategic plan to bring an ancient disease into the 21st century. PMID- 22091567 TI - The importance of delirium: economic and societal costs. AB - Although a number of studies have documented the negative clinical and economic consequences of delirium, interventions to prevent and treat delirium are infrequently implemented. The importance of delirium may continue to be underestimated until its societal and economic effects are documented. The current article outlines the existing literature related to long-term sequelae and costs associated with delirium and stresses the importance of such research in prompting recognition, prevention, and treatment efforts that could reduce the effect of delirium and improve quality of life for older adults and their caregivers. PMID- 22091568 TI - The Johns Hopkins Delirium Consortium: a model for collaborating across disciplines and departments for delirium prevention and treatment. AB - Delirium is an important syndrome affecting inpatients in various hospital settings. This article focuses on multidisciplinary and interdepartmental collaboration to advance efforts in delirium clinical care and research. The Johns Hopkins Delirium Consortium, which includes members from the disciplines of nursing, medicine, rehabilitation therapy, psychology, and pharmacy within the departments and divisions of anesthesiology, geriatrics, oncology, orthopedic surgery, psychiatry, critical care medicine, and physical medicine and rehabilitation at the Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center, is one model of such collaboration. This article describes the process involved in developing functional collaboration around delirium and highlights projects, opportunities, and challenges resulting from them. PMID- 22091569 TI - Delirium and sedation recognition using validated instruments: reliability of bedside intensive care unit nursing assessments from 2007 to 2010. AB - OBJECTIVES: To describe the reliability and sustainability of delirium and sedation measurements of bedside intensive care unit (ICU) nurses. DESIGN: Prospective cohort study. SETTING: A tertiary care academic medical center. PARTICIPANTS: Five hundred ten ICU patients from 2007 to 2010; 627 bedside nurses. MEASUREMENTS: Bedside nurses and well-trained reference-rater research nurses independently measured delirium and sedation levels in routine care. Bedside nurses were instructed to use the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) every 12 hours to measure delirium and the Richmond Agitation-Sedation Scale (RASS) every 4 hours to measure sedation. CAM-ICU and RASS assessment agreement were computed using weighted kappa statistics across the entire population and subgroups (e.g., ICU type). Sensitivity and specificity of bedside nurse identification of delirium were calculated to understand sources of discordance. RESULTS: Six thousand one hundred ninety-eight CAM-ICU and 6,880 RASS measurement pairs obtained on 3,846 patient-days. For CAM-ICU measurements, agreement between bedside and research nurses was substantial (weighted kappa = 0.67, 95% confidence interval (CI) = 0.66-0.70) and stable over 3 years of data collection. RASS measures also demonstrated substantial agreement (weighted kappa = 0.66, 95% CI = 0.64-0.68), which was stable across all years of data collection. The sensitivity of delirium nurse assessments was 0.81 (95% CI = 0.78 0.83), and the specificity was 0.81 (95% CI = 0.78-0.85). CONCLUSION: Bedside nurse measurements of delirium and sedation are sustainable and reliable sources of information. These measures can be used for clinical decision-making, quality improvement, and quality measurement activities. PMID- 22091570 TI - Biomarkers for delirium--a review. AB - To improve delirium recognition and care, numerous serum biomarkers have been investigated as potential tools for risk stratification, diagnosis, monitoring, and prognostication of delirium. The literature was reviewed, and no evidence was found to support the clinical use of any delirium biomarker, although certain biomarkers such as S-100 beta and insulin-like growth factor-1 and inflammatory markers have shown some promising results that need to be evaluated in future studies with appropriate sample size, prospective designs, and in a more generalizable population. PMID- 22091571 TI - Vulnerability: the crossroads of frailty and delirium. AB - Frailty and delirium, although seemingly distinct syndromes, both result in significant negative health outcomes in older adults. Frailty and delirium may be different clinical expressions of a shared vulnerability to stress in older adults, and future research will determine whether this vulnerability is age related, pathological, genetic, environmental, or most likely, a combination of all of these factors. This article explores the clinical overlap of frailty and delirium, describes possible pathophysiological mechanisms linking the two, and proposes research opportunities to further knowledge of the interrelationships between these important geriatric syndromes. Frailty, a diminished ability to compensate for stressors, is generally viewed as a chronic condition, whereas delirium is an acute change in attention and cognition, but there is a developing literature on transitions in frailty status around acute events, as well as on delirium as a chronic, persistent condition. If frailty predisposes an individual to delirium, and delirium delays recovery from a stressor, then both syndromes may contribute to a downward spiral of declining function, increasing risk, and negative outcomes. In addition, frailty and delirium may have shared pathophysiology, such as inflammation, atherosclerosis, and chronic nutritional deficiencies, which will require further investigation. The fields of frailty and delirium are rapidly evolving, and future research may help to better define the interrelationship of these common and morbid geriatric syndromes. Because of the heterogeneous pathophysiology and presentation associated with frailty and delirium, typical of all geriatric syndromes, multicomponent prevention and treatment strategies are most likely to be effective and should be developed and tested. PMID- 22091572 TI - Antipsychotics in the treatment of delirium in older hospitalized adults: a systematic review. AB - OBJECTIVES: To examine evidence of the efficacy of antipsychotics in the treatment of delirium in older hospitalized adults. DESIGN: Systematic literature review. SETTING: Hospital. PARTICIPANTS: Older adults with delirium. MEASUREMENTS: The MEDLINE (January 1980-December 2010) and Cochrane Databases were searched using the keywords "delirium" and "antipsychotics." References of review articles were reviewed to identify additional studies. Study selection criteria included prospective design, more than 10 participants (in treatment arms), mean age 60 and older, standardized criteria for diagnosing delirium, and validated delirium rating scales for reporting outcomes. RESULTS: Thirteen articles met selection criteria: six single-agent and seven comparison studies. Of these, eight (62%) had fewer than 25 participants in treatment arms, 10 (77%) recruited participants from psychiatry referrals, and eight (62%) did not clearly describe their screening methods. All single-agent studies were open-label studies. Of the comparison studies, five (71%) used randomization, but only one of these (a placebo-controlled study) used adequate allocation concealment methods, and only one other study (comparing two antipsychotics) described a double-blind method in detail. In the only placebo-controlled study (which was stopped early), no statistically significant differences in mean delirium severity scores were found at individual time points (Days 2, 3, 4, 7, 10). The other 12 studies reported improvements in delirium severity or resolution of delirium based on cutoff scores of the scales, but it is not clear from any of these studies what the natural course of delirium would have been without use of antipsychotics. CONCLUSION: Because of severe methodological limitations, the studies in this review do not support the use of antipsychotics in the treatment of delirium in older hospitalized adults. Additional well-designed randomized placebo-controlled trials are needed. PMID- 22091573 TI - Association between prescribing of anticholinergic medications and incident delirium: a cohort study. AB - OBJECTIVES: To describe the association between anticholinergic medications and incident delirium in hospitalized older adults with cognitive impairment and to test the hypothesis that anticholinergic medications would increase the risk of incident delirium. DESIGN: Observational cohort study. SETTING: Urban public hospital in Indianapolis, Indiana. PARTICIPANTS: One hundred forty-seven participants aged 65 and older with cognitive impairment who screened negative for delirium at the time of admission to a general medical ward. MEASUREMENTS: Cognitive function at the time of admission was assessed using the Short Portable Mental Status Questionnaire (SPMSQ). Anticholinergic medication orders between the time of admission and the final delirium assessment were evaluated. Anticholinergic medication orders were identified using the Anticholinergic Cognitive Burden Scale. Delirium was assessed using the Confusion Assessment Method. RESULTS: Fifty-seven percent of the cohort received at least one order for possible anticholinergic medications, and 28% received at least one order for definite anticholinergic medications. The incident rate for delirium was 22% of the entire cohort. After adjusting for age, sex, race, baseline SPMSQ score, and Charlson Comorbidity Index, the odds ratio (OR) for developing delirium in those with orders for possible anticholinergic medications was 0.33 (95% confidence interval (CI) = 0.10-1.03). The OR for developing delirium among those with orders for definite anticholinergic medications was 0.43 (95% CI = 0.11-1.63). CONCLUSION: The results did not support the hypothesis that prescription of anticholinergic medications increases the risk of incident delirium in hospitalized older adults with cognitive impairment. This relationship needs to be established using prospective study designs with medication dispensing data to improve the performance of predictive models of delirium. PMID- 22091574 TI - Pilot randomized trial of donepezil hydrochloride for delirium after hip fracture. AB - OBJECTIVES: To determine whether donepezil hydrochloride can reduce the prevalence and severity of delirium in older adults undergoing hip fracture repair. DESIGN: Pilot double-masked randomized placebo-controlled trial. SETTING: Large academic medical center. PARTICIPANTS: Sixteen individuals aged 70 and older with hip fracture. INTERVENTION: Donepezil 5 mg or placebo was randomly allocated and initiated within 24 hours of surgery, preoperatively or postoperatively. Daily treatment was continued for 30 days or until side effects or the clinical situation required termination. MEASUREMENTS: All outcomes were ascertained masked to treatment status. Information on drug tolerability and safety was obtained from the participant, nurse, and medical record. Delirium presence and severity were measured during daily hospital interviews and at 2, 4, and 6 weeks after surgery after a standardized assessment using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale (MDAS). RESULTS: Participants in the donepezil and placebo arms had similar baseline characteristics. Participants in the donepezil arm experienced significantly more side effects. In longitudinal models, there were no significant differences between the donepezil and placebo arms with regard to delirium presence over time (odds ratio = 0.9, 95% confidence interval (CI) = 0.4-2.3) or delirium severity over time (effect size = -0.2 on 30-point MDAS scale, 95%CI = -1.5-1.2). CONCLUSION: Participants randomized to donepezil had no significant improvement in delirium presence or severity but experienced more side effects. Overall, sufficient evidence was not found from this pilot study to warrant a definitive Phase III trial. PMID- 22091575 TI - Validation of a medical record-based delirium risk assessment. AB - OBJECTIVES: To improve identification of patients at high risk for delirium, this study developed a chart abstraction tool for delirium risk and validated the tool against clinical expert diagnosis of delirium. DESIGN: Prospective cohort study. SETTING: Tertiary Veterans Affairs hospital in New England. PARTICIPANTS: One hundred veterans admitted to the medical service. MEASUREMENTS: While admitted, each participant underwent serial assessments for delirium by a clinical expert. Using the four criteria of a validated delirium prediction rule (cognitive impairment, sensory deficit, severe illness, and dehydration), chart review terms were selected for each criterion, and delirium risk was the sum of criteria present (range: 0-4; 4 = worst). After discharge, a nurse blinded to the expert's diagnosis completed the chart tool. RESULTS: The participants were mostly male (94%) and older (mean age 81 +/- 7), and 23% developed overall delirium (14% incident). The rate of overall delirium was 11% in participants with zero risk factors, 18% in those with one or two, and 50% in those with three or four (P = .01; c-statistic 0.65, 95% confidence interval (CI) = 0.54-0.76). For incident delirium, the rates were 11%, 13%, and 25%, respectively (P = .53; c-statistic 0.56, 95% CI = 0.42-0.74). Discharge to a rehabilitation center or nursing home increased with increasing delirium risk (0%, 18%, 60%, P = .02). CONCLUSION: A chart abstraction tool was effective at identifying overall delirium risk but not incident delirium risk. Although the tool cannot replace clinical assessment and diagnosis of delirium, the use of this tool as an educational, clinical, or quality measurement aid warrants additional study. PMID- 22091576 TI - Matching the environment to patients with delirium: lessons learned from the delirium room, a restraint-free environment for older hospitalized adults with delirium. AB - Delirium is associated with several negative outcomes and is not always preventable. Current practices for the management of older hospitalized adults with delirium, such as one-on-one sitters, antipsychotic medications, and physical restraints, have limited effectiveness or potential health risks. An alternative management model, called the Delirium Room (DR), is a four-bed patient room (within an Acute Care for Elders (ACE) Unit) that provides 24-hour nursing care, emphasizes nonpharmacological approaches, and is completely free of physical restraints. This article is based on 13 years of experience at two hospitals. The authors have found that a restraint-free environment can be achieved; "tolerate, anticipate, and don't agitate" (the T-A-DA method) are the core principles of the nonpharmacological approach that go beyond the traditional strategies of management (such as reorientation); based on observational data, it appears that negative outcomes associated with delirium, such as loss of function, longer hospital stay, and greater mortality, can be decreased to levels seen in individuals without delirium; and based on limited data, it appears that the rate of falls is at least not higher in the DR than in the ACE unit overall. The limitations of the DR model include lack of randomized controlled trials and the inability to determine which component of the model provides its benefits. PMID- 22091577 TI - Postoperative delirium and functional decline after noncardiac surgery. AB - OBJECTIVES: To determine whether delirium after noncardiac surgery is associated with functional decline 3 months postoperatively. DESIGN: Secondary analysis of a prospective study. SETTING: Thirteen hospitals in eight countries. PARTICIPANTS: One thousand two hundred eighteen individuals aged 60 and older undergoing noncardiac surgery. MEASUREMENTS: Participants were interviewed before surgery and 3 months postoperatively using six items pertaining to social and independent function. Functional decline was determined according to a loss in function in at least one item at the 3-month assessment from baseline. Postoperatively, a trained interviewer assessed delirium daily using a standardized battery. The primary outcome of this analysis was an examination of the risk of functional decline with delirium. RESULTS: Of the 948 participants who completed functional assessment at 3 months, 20% (n = 189) had a decline in function. In unadjusted analysis, postoperative delirium increased the odds of functional decline (odds ratio (OR) = 2.4, 95% confidence interval (CI) = 1.4-4.2). After adjustment for age, sex, education, cognition, and surgery duration, delirium remained associated with functional decline (OR = 2.1, 95% CI = 1.2-3.8). CONCLUSION: Although considered an acute event, delirium can have lasting functional consequences. Clinicians should give strong consideration to preoperative delirium risk assessment, delirium prevention strategies, and delirium surveillance programs after noncardiac surgery. PMID- 22091578 TI - Theory of mind through the ages: older and middle-aged adults exhibit more errors than do younger adults on a continuous false belief task. AB - Theory of mind (ToM), or the ability to understand mental states, is a fundamental aspect of social cognition. Previous research has documented marked advances in ToM in preschoolers, and declines in ToM in older-aged adults. In the present study, younger (n=37), middle-aged (n=20), and older (n=37) adults completed a continuous false belief task measuring ToM. Middle-aged and older adults exhibited more false belief bias than did younger adults, irrespective of language ability, executive function, processing speed, and memory. The authors conclude that ToM declines from younger to older adulthood, independent of age related changes to domain-general cognitive functioning. PMID- 22091579 TI - Age differences in valence judgments of emotional faces: the influence of personality traits and current mood. AB - Previous research on emotion processing revealed a positivity bias that progressively evolves across the adult age range. This study obtained gradual valence judgments of emotional faces across the adult age span, to see whether this positivity bias persists when positive and negative stimuli are matched for arousal; and whether bias relates to personality traits or to current mood. With increasing age subjects judged negative and neutral faces less negatively. Further, younger participants scoring high in "agreeableness" and "conscientiousness" scales showed a positivity bias when judging positive faces, suggesting an association of the positivity effect with trait variables. PMID- 22091580 TI - The contribution of set switching and working memory to sentence processing in older adults. AB - This study evaluates the involvement of switching skills and working-memory capacity in auditory sentence processing in older adults. The authors examined 241 healthy participants, aged 55 to 88 years, who completed four neuropsychological tasks and two sentence-processing tasks. In addition to age and the expected contribution of working memory, switching ability, as measured by the number of perseverative errors on the Wisconsin Card Sorting Test, emerged as a strong predictor of performance on both sentence-processing tasks. Individuals with both low working-memory spans and more perseverative errors achieved the lowest accuracy scores. These findings are consistent with compensatory accounts of successful performance in older age. PMID- 22091581 TI - Older adults capitalize on contextual information to guide search. AB - Much has been learned about the age-related cognitive declines associated with the attentional processes that utilize perceptual features during visual search. However, questions remain regarding the ability of older adults to use scene information to guide search processes, perhaps as a compensatory mechanism for declines in perceptual processes. The authors had younger and older adults search pseudorealistic scenes for targets with strong or no spatial associations. Both younger and older adults exhibited reaction time benefits when searching for a target that was associated with a specific scene region. Eye movement analyses revealed that all observers dedicated most of their time to scanning target consistent display regions and that guidance to these regions was often evident on the initial saccade of a trial. Both the benefits and costs related to contextual information were larger for older adults, suggesting that this information was relied on heavily to guide search processes towards the target. PMID- 22091582 TI - Context processing in aging: older mice are impaired in renewal of extinguished fear. AB - Fear conditioning, extinction, and renewal were evaluated in adult (6-month-old) and aging (17-month-old) male C57Bl/6 mice. Mice were subjected to five tone shock trials and later exposed to 150 tone-alone trials. Thereafter, all mice showed little fear in the extinction context. Adult mice demonstrated return of fear in a distinct context (renewal) but aging mice did not. Aging mice showed normal shock sensitivity, tone fear learning, and extinction. Aging mice thus exhibited a very selective deficit in the contextual gating of extinguished fear. This contextual gating deficit may reflect age-related pathology in the hippocampus and prefrontal cortex. PMID- 22091584 TI - Experimental methods and prediction with COSMO-RS to determine partition coefficients in complex surfactant systems. AB - Surfactant-based separation processes are a promising alternative to conventional organic solvent processes. A crucial parameter to describe the efficiency of such processes is the partition coefficient between the surfactant aggregates (micelles) and the aqueous bulk phase. In this work, several experimental methods to determine these partition coefficients (micellar liquid chromatography, micellar enhanced ultrafiltration, and cloud point extraction) are evaluated and compared. In addition, these results are compared to predictions with the thermodynamic model COSMO-RS. In particular, systems with the nonionic surfactant TritonX-100 are studied. The partition equilibria of various solutes (pyrene, naphthalene, phenanthrene, phenol, 3-methoxyphenol, and vanillin) and the influence of different additives (alcohols) are investigated. All experimental methods show very good reproducibility. Moreover, the results from different methods are in good agreement, supplementing one another concerning the temperature ranges. Notably, the COSMO-RS model is capable of predicting partition coefficients between micelles and water in the investigated temperature range and at different alcohol concentrations. The results demonstrate the potential of the model COSMO-RS to facilitate the selection of optimized process parameters for a given separation problem. By predicting partition equilibria in multicomponent systems, the selection of surfactant, temperature, and appropriate additives can be facilitated. PMID- 22091585 TI - Guided transport of water droplets on superhydrophobic-hydrophilic patterned Si nanowires. AB - We present a facile method to fabricate hydrophilic patterns in superhydrophobic Si nanowire (NW) arrays for guiding water droplets. The superhydrophobic Si NW arrays were obtained by simple dip-coating of dodecyltrichlorosilane (DTS). The water contact angles (CAs) of DTS-coated Si NW arrays drastically increased and saturated at the superhydrophobic regime (water CA >= 150 degrees ) as the lengths of NWs increased. The demonstrated superhydrophobic surfaces show an extreme water repellent property and small CA hysteresis of less than 7 degrees , which enable the water droplets to easily roll off. The wettability of the DTS coated Si NW arrays can be converted from superhydrophobic to hydrophilic via UV enhanced photodecomposition of the DTS, and such wettability conversion was reproducible on the same surfaces by repeating the DTS coating and photodecomposition processes. The resulting water guiding tracks were successfully demonstrated via selective patterning of the hydrophilic region on superhydrophobic Si NW arrays, which could enable water droplets to move along defined trajectories. PMID- 22091586 TI - Stepwise effective molarities in porphyrin oligomer complexes: preorganization results in exceptionally strong chelate cooperativity. AB - Complexes of zinc porphyrin oligomers with multivalent ligands can be denatured by adding a large excess of a monodentate ligand, such as quinuclidine. We have used denaturation titrations to determine the stabilities of the complexes of a cyclic zinc-porphyrin hexamer with multidentate ligands with two to six pyridyl coordination sites. The corresponding complexes of linear porphyrin oligomers were also investigated. The results reveal that the stepwise effective molarities (EMs) for the third through sixth intramolecular coordination events with the cyclic hexamer are extremely high (EM = 10(2)-10(3) M), whereas the values for the linear porphyrin oligomers are modest (EM ~ 0.05 M). The speciation profiles for the denaturation reactions demonstrate that intermediate species are not significantly populated and that these equilibria are well described by a highly cooperative two-state model. PMID- 22091587 TI - Identification of mitochondrial electron transport chain-mediated NADH radical formation by EPR spin-trapping techniques. AB - The mitochondrial electron transport chain (ETC) is a major source of free radical production. However, due to the highly reactive nature of radical species and their short lifetimes, accurate detection and identification of these molecules in biological systems is challenging. The aim of this investigation was to determine the free radical species produced from the mitochondrial ETC by utilizing EPR spin-trapping techniques and the recently commercialized spin-trap, 5-(2,2-dimethyl-1,3-propoxycyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO). We demonstrate that this spin-trap has the preferential quality of having minimal mitochondrial toxicity at concentrations required for radical detection. In rat heart mitochondria and submitochondrial particles supplied with NADH, the major species detected under physiological pH was a carbon-centered radical adduct, indicated by markedly large hyperfine coupling constant with hydrogen (a(H) > 2.0 mT). In the presence of the ETC inhibitors, the carbon centered radical formation was increased and exhibited NADH concentration dependency. The same carbon-centered radical could also be produced with the NAD biosynthesis precursor, nicotinamide mononucleotide, in the presence of a catalytic amount of NADH. The results support the conclusion that the observed species is a complex I derived NADH radical. The formation of the NADH radical could be blocked by hydroxyl radical scavengers but not SOD. In vitro experiments confirmed that an NADH-radical is readily formed by hydroxyl radical but not superoxide anion, further implicating hydroxyl radical as an upstream mediator of NADH radical production. These findings demonstrate the identification of a novel mitochondrial radical species with potential physiological significance and highlight the diverse mechanisms and sites of production within the ETC. PMID- 22091588 TI - Orienting to external versus internal regions of space: consequences of attending in advance versus after the fact. AB - We examined effects of knowing where to attend to-be-remembered information in advance versus after the fact. Participants performed a visuospatial short-term memory task with orienting cues that appeared before or after a memory display and reported whether a probe item had appeared on the cued side. Event-related potentials (ERPs) were recorded for cues, memory displays, and probes. Performance was better in precued versus postcued conditions. ERPs to orienting cues and memory displays were lateralized in relation to the direction of attention in precued but not postcued conditions. ERPs to recognition probes were lateralized, but this was similar between pre- and postcued conditions. Results suggest that we can orient visuospatial attention outwardly to external events and inwardly to remembered events alike, but knowing where to attend information in advance gives a bigger boost to brain and behavior. PMID- 22091589 TI - Developing predictive biomarkers for dementia of Parkinson's disease. PMID- 22091590 TI - Charting the path for early diagnosis and prevention of Alzheimer's disease. PMID- 22091592 TI - Eslicarbazepine acetate for partial-onset seizures. AB - Eslicarbazepine acetate (ESL), a new voltage-gated sodium channel blocker that is chemically related to carbamazepine and partially metabolized to oxcarbazepine, has attracted attention as results of previous Phase II and III studies demonstrated and confirmed efficacy and tolerability of ESL 800 and 1200 mg once daily as add-on therapy for adult patients with drug-resistant partial-onset seizures. In children, efficacy data point towards a dose-dependent decrease in seizure frequency and tolerability analyses showed a low incidence of mild drug related adverse effects at 5 and 15 mg/kg/day. The most frequently reported adverse effects were dizziness, somnolence, headache, diplopia, nausea and vomiting. The convenience of once-daily dosing and a short/simple titration regimen in combination with a comparative efficacy and tolerability profile might promote ESL as a valid alternative to the current adjunctive antiepileptic drug therapy armamentarium for drug-resistant partial seizures in adults. Since clinical trials in children and adolescents on ESL efficacy and safety are ongoing and data already published are far from conclusive, the therapeutic value of ESL in this special population has to be established in the near future. PMID- 22091593 TI - Treating multiple sclerosis with natalizumab. AB - Natalizumab is the first monoclonal antibody approved for the treatment of relapsing multiple sclerosis. Pivotal trials demonstrated the efficacy of natalizumab on clinical and paraclinical measures of disease activity and disability progression. Although a direct comparison has not been performed yet, natalizumab seems to be more efficacious than the currently available immunomodulant drugs, such as IFN-beta and glatiramer acetate. Despite its efficacy, the occurrence of an increased risk of progressive multifocal leukoencephalopathy with the treatment, raises concerns about its widespread use in multiple sclerosis patients. This paper provides an overview of the most relevant results from the Phase I-IV studies on natalizumab and highlights the challenges addressed to minimize and manage its adverse events in clinical practice. PMID- 22091594 TI - Lithium treatment in amyotrophic lateral sclerosis: do we have enough trials? AB - Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder; riluzole is marginally effective, and as a consequence a large number of trials are regularly reported. Lithium raised marked enthusiasm based on the report of a pilot study that suggested very positive results. Two previous trials were negative, applying a different methodology. The reviewed article reports the results of a third trial using a historical control group. In this trial, lithium was detrimental to ALS progression. Two more trials testing lithium in ALS are in progress. This study is discussed in the context of the great competitive effort that was derived from the unsupported hope created by a false-positive preliminary study. PMID- 22091595 TI - Translational neuroscience in pediatric bipolar disorder. AB - While controversial and often confounded with other forms of psychopathology, recent studies have shown that bipolar disorder (BD) is on the rise in children and adolescents. Research has made important strides in advancing our understanding of the phenomenology, neural underpinnings and treatment outcomes for BD youths. However, there is an increasing need to unite these domains to identify potential neural effects and predictors of treatment outcome. Pavuluri et al. have conducted such a study, evaluating the neural effects of divalproex or risperidone for pediatric BD. The future is likely to bring more of such studies, potentially resulting in a biomarker augmented approach to the diagnosis and treatment of pediatric BD. PMID- 22091597 TI - Metal attenuating therapies in neurodegenerative disease. AB - The clinical and pathological spectrum of neurodegenerative diseases is diverse, although common to many of these disorders is the accumulation of misfolded proteins, with oxidative stress thought to be an important contributing mechanism to neuronal damage. As a corollary, transition metal ion dyshomeostasis appears to play a key pathogenic role in a number of these maladies, including the most common of neurodegenerative diseases. In this review, studies spanning a wide variety of neurodegenerative disorders are presented with their involvement of transition metals compared and contrasted, including more detailed treatise in relation to Alzheimer's disease, Parkinson's disease and prion diseases. For each of these diseases, a discussion of the evolving scientific rationale for the development of therapies aimed at ameliorating the detrimental effects of transition metal dysregulation, including results from various human trials, is then provided. PMID- 22091598 TI - Problems and controversies in status epilepticus: a review and recommendations. AB - Status epilepticus (SE) is a neurologic emergency that require immediate vigorous treatment in order to prevent serious morbidity or even death. Several investigators have suggested that the underlying etiology is the primary determinant of outcome. We believe that this may be true in aggressively treated SE, but not when the treatment is less than optimal. In this article, we will discuss the factors that have been implicated in affecting SE outcomes, and argue, on the basis of both human and experimental animal data, that aggressive treatment is necessary and appropriate for all presentations of SE in order to maximize the probability of a successful outcome even when the etiology suggests a poor prognosis. PMID- 22091599 TI - The use of recently approved antiepileptic drugs: use with caution, use in refractory patients or use as first-line indications? AB - Approximately 50% of patients with newly diagnosed epilepsy achieve immediate remission, and up to 50% enter terminal remission with first-generation antiepileptic drugs. However, 20-30% of cases are still refractory to current treatments. This population is the target of newer antiepileptic drugs and other compounds in development. The licensing of newer antiepileptic drugs represents an advance in the development of more manageable products and the control of several disturbing adverse drug reactions of the older compounds. However, despite the development of several new antiepileptic drugs, the efficacy and tolerability of drug treatment of epilepsy has not substantially improved in terms of effectiveness and risk-benefit and cost-benefit profiles. Newer antiepileptic drugs are, at best, equivalent in efficacy to their predecessors, but some of them are more manageable and better tolerated. However, the use of a first-generation compound at low doses in newly diagnosed patients is still preferable because the disease can be as well-controlled and the incidence of intolerable side effects is minimized. Newer generation compounds should be used as alternative treatments in patients who are nonresponding to first-generation drugs and in those for whom these drugs are contraindicated or poorly tolerated. As an exception, some new-generation drugs are a valuable option in the presence of comorbidities known to respond to these products or in patients with selected epilepsy syndromes. In light of the heterogeneity and the complexity of the mechanisms underlying epileptic seizures, the future of drug development will be the discovery of drugs efficacious for the treatment of selected epilepsy syndromes or, more specifically, targeting genetic defects leading to molecular abnormalities. PMID- 22091596 TI - Pathways towards an effective immunotherapy for Parkinson's disease. AB - Immunizations that target specific types of immune responses are used commonly to prevent microbial infections. However, a range of immune responses may prove necessary to combat the ravages of neurodegenerative diseases. The goal is to eliminate the 'root' cause of neurodegenerative disorders, misfolded aggregated proteins, while harnessing adaptive immune responses to promote neural repair. However, immunization strategies used to elicit humoral immune responses against aberrant brain proteins have yielded mixed success. While specific proteins can be cleared, the failures in halting disease progression revolve, in measure, around adaptive immune responses that promote autoreactive T cells and, as such, induce a meningoencephalitis, accelerating neurodegeneration. Thus, alternative approaches for protein clearance and neural repair are desired. To this end, our laboratories have sought to transform autoreactive adaptive immune responses into regulatory neuroprotective cells in Parkinson's disease. In this context, induction of immune responses against modified brain proteins serves to break immunological tolerance, while eliciting adaptive immunity to facilitate neuronal repair. How to harness the immune response in the setting of Parkinson's disease requires a thorough understanding of the role of immunity in human disease and the ways to modify such immune responses to elicit therapeutic gain. These are discussed in this review. PMID- 22091600 TI - Memory problems in dementia: adaptation and coping strategies and psychosocial treatments. AB - Memory problems are generally quite prominent in dementia and they have a significant impact on everyday functioning. Medication developed for Alzheimer's disease, for example, acetylcholinesterase inhibitors, can slow down the increase of cognitive impairment for a while. In addition to pharmacotherapy, psychosocial treatment methods are also used, some of which have a positive effect on cognition, for example, cognitive rehabilitation, cognitive stimulation therapy and movement therapy. However, more research is needed. This article first describes the consequences of memory problems on the everyday life of people with dementia and summarizes research findings on how people with dementia experience and cope with their illness. We then discuss the most frequently applied psychosocial treatments for cognitive problems in dementia. PMID- 22091601 TI - Molecular PET imaging in multicenter Alzheimer's therapeutic trials: current trends and implementation strategies. AB - Current therapeutic approaches for Alzheimer's disease (AD) have evolved to target specific molecular biological, metabolic and neuropathologic hallmarks of the disease. Since these approaches are hypothesized to be most effective at the earliest stages of the degenerative process, the ability to accurately detect and monitor progression of AD pathology and metabolic changes in vivo may accelerate the discovery and development of disease-modifying drugs. The use of molecular imaging biomarkers can not only enhance diagnostic accuracy and facilitate patient selection/stratification, but can also serve as key outcomes for clinical trials. In this review, we discuss emerging trends in the use of PET in AD drug development and provide a roadmap for harnessing its promise in multicenter clinical trials. PMID- 22091603 TI - Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy. AB - The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients. We performed the present study to investigate the efficacy and tolerability of oral loading of oxcarbazepine in patients with recurrent seizures, or after temporary discontinuation of AEDs for diagnostic or presurgical evaluation of epilepsy. Forty adult patients were studied and oxcarbazepine was administered orally at a single loading dosage of 30 mg/kg. The plasma levels of oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), were measured, and clinical assessment of adverse events was performed at 2, 4, 6, 8, 10, 12, 16, and 24 h after oral loading of oxcarbazepine. Approximately two-thirds of patients reached effective levels of MHD 2 h after receiving the oral loading, and all patients reached effective levels 4 h after oxcarbazepine administration. Most patients maintained therapeutic MHD levels for at least 16 h. Almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 h. Our study shows that oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of MHD in patients with epilepsy, and is a useful option in selected patients with recurrent seizures, or after temporary discontinuation of AEDs. PMID- 22091604 TI - Review of "depression in the elderly-simulated patient small group activity". AB - This activity teaches knowledge and skills regarding the assessment and management of geriatric depression to second-year medical students. Students actively participate in a standardized patient scenario with a "collateral source," which the authors define as a relative, friend, neighbor, healthcare power of attorney, or healthcare provider of a cognitively impaired patient who can provide additional history that might be more accurate than that obtained from the patient. Students also discuss proposed physical examination items, formulate a management plan with assistance from a handout on geriatric depression and facilitation by a faculty member, and receive feedback from the standardized patient and a "collateral source." This activity is designed to take c approximately 2 hours to administer to small groups of learners and emphasizes that depression often presents atypically in older adults. PMID- 22091605 TI - Pharmacokinetic assessment of ketanserin in the horse. AB - The purpose of this study was to determine the pharmacokinetics (PK) of the 5 HT(2A) receptor antagonist ketanserin in healthy adult horses, and to develop a computational model that could be used to optimize dosing. Plasma concentrations of ketanserin were determined using liquid chromatography with mass spectrometry after single and multiple intravenous administration in the horse. A two compartment linear pharmacokinetic model described the plasma concentration-time profile of ketanserin after single and multiple doses in healthy horses; the terminal half-life was 11.5 h; steady-state volume of distribution was 10.5 L/kg; AUC was 115 ng . h/mL; and clearance was 0.87 L/h/kg. Model simulations followed by the examination in three healthy horses suggest 0.3 mg/kg q.8 h exhibited linear PK and produced consistent systemic blood concentrations of ketanserin above 3 ng/mL. PMID- 22091609 TI - Recent fertility declines in Hong Kong: the role of the changing age structure. AB - Abstract The birth rate in Hong Kong fell rapidly from 1961 to 1966: from 35.5 in 1961 to 25.8 in 1966 1 These rates are based on corrected estimates of population and of births made after the 1966 census. They differ somewhat from rates published before that, because the earlier rates had not been adjusted for some underregistration of births and had been calculated on larger population bases than proved to be justified by the census. - a decline of27%. Such a decline deserves special attention, because there are only a few examples of such trends in poor, high-fertility populations since World War II. We have just begun to find evidence of such declines in a few of the other rapidly developing countries of Asia: Taiwan, Korea, Singapore, and Malaysia. PMID- 22091610 TI - Son survivorship motivation and family size in India: A computer simulation. AB - Abstract Many sociologists and demographers have argued that the comparatively large families of six to eight children found in rural India to-day result from ignorance of family planning methods, from tradition, and from passive indecision; and that large reductions in the Indian growth rate to Western levels would occur spontaneously if each Indian family were given access to birth control facilities, materials and information. On the other hand, it has been maintained that large family sizes are functional for rural families in India and other developing countries; and that they result from conscious or unconscious choice based upon enlightened self-interest. PMID- 22091611 TI - Fertility and nuptiality changes in Spain from the late 18th to the early 20th century. AB - Abstract 3.1. A regional approach often reveals features of population trends not evident in national data. We have already pointed out that the 1768 census followed the ecclesiastical sub-divisions of the country; therefore its territorial data are not comparable with those derived from later enumerations. The 1787 and 1797 censuses, on the other hand, were based on civil sub-divisions, which can be compared, when aggregated, with later censuses of the modern statistical era. PMID- 22091606 TI - Mechanisms of Toxoplasma gondii persistence and latency. AB - Toxoplasma gondii is an obligate intracellular protozoan parasite that causes opportunistic disease, particularly in immunocompromised individuals. Central to its transmission and pathogenesis is the ability of the proliferative stage (tachyzoite) to convert into latent tissue cysts (bradyzoites). Encystment allows Toxoplasma to persist in the host and affords the parasite a unique opportunity to spread to new hosts without proceeding through its sexual stage, which is restricted to felids. Bradyzoite tissue cysts can cause reactivated toxoplasmosis if host immunity becomes impaired. A greater understanding of the molecular mechanisms orchestrating bradyzoite development is needed to better manage the disease. Here, we will review key studies that have contributed to our knowledge about this persistent form of the parasite and how to study it, with a focus on how cellular stress can signal for the reprogramming of gene expression needed during bradyzoite development. PMID- 22091612 TI - Changing vital rates and age distributions. AB - Abstract In a time of rapid change in birth and death rates demographers need to know the consequences of such changes for age distribution. Does the fall in death rates tend to make the age distribution older? It certainly enables individuals to grow older, but for population aggregates the effect depends on the ages at which mortality improves. Coale, Stolnitz, Schwarz, Lorimer, the United Nations and other writers have investigated trends in age-specific birth and death rates. In particular they have demonstrated that the falling mortality which is now nearly universal does not generally make the population older and sometimes makes it younger. The present article contributes a technique for further examination of this phenomenon. PMID- 22091613 TI - Determinants of birth intervals and their means. AB - Abstract 1. The duration of post-partum infecundity; 2. Fecundability; 3. Duration of pregnancy. PMID- 22091614 TI - Return migration from Canada to Britain. AB - Abstract Statistics of migrants returning from Canada to Britain and re registering for national insurance purposes are compared with labour force immigrants entering Canada between 1956 and 1965. Short and long-term indices are calculated which suggest that return migration has been increasing since 1960. A sample survey carried out in 1962-63 distinguishes three types of returning migrant: (a) quasi-migrants who originally planned to return to Britain; (b) permanent repatriates who originally intended to settle in Canada but now expect to remain in Britain; (c) transilient migrants who exhibit a high propensity to move backwards and forwards between two or more countries without becoming permanently rooted in anyone. The demographic, economic and social characteristics of the three types are described. A further comparison is made between migrants who plan to settle in Britain, those who intend to come back again to Canada, and those who are uncertain of their future plans or who intend to move on to a third country. PMID- 22091615 TI - A note on the population of Iran, 1900-1966. AB - Abstract The first national census of Iran was held in November 1956, and the second in November 1966. Prior to 1956 the only official population records that existed were figures for an urban headcount (held between June 1939 and August 1941) and the statistics of the Civil Registration Office (C.R.O.), which started operations in 1928. PMID- 22091616 TI - A note of correction with reference to parameters of the menstrual cycle and the efficiency of rhythm methods of contraception. AB - Abstract Owing to a misunderstanding in regard to the data sheets, all the references to the pre- and post-ovulatory phases in Dr. Marshall's data in my paper should be interchanged. The following is a list of conclusions which may be drawn from that study: 1. Although the Farris Test is probably less efficient than had formerly been thought, there is no evidence that it is biased. 2. Within individual histories, pre-ovulatory phase variance usually exceeds post ovulatory phase variance. 3. The variance of mean pre-ovulatory phase exceeds that of mean post-ovulatory phase among a group of women. 4. Within a group of women, there seems to be no appreciable correlation between mean pre-ovulatory and mean post-ovulatory phase. 5. It is possible that there is a true underlying positive correlation between pre- and post-ovulatory phases within a single menstrual history. 6. The standard error of the RB.T. test was estimated to exceed ?6 days. 7. The variances of the phases within individual histories are probably positively correlated, so it seems that in general a variable post-ovulatory phase is not favourable to the outcome of the practice of rhythm. PMID- 22091619 TI - Acquired bilateral melanosis of the neck in perimenopausal women. AB - BACKGROUND: Acquired bilateral patchy or mottled pigmentation of the neck has occasionally been observed. OBJECTIVE: To investigate the clinical and histopathological characteristics of this pigmentation. METHODS: Fourteen patients were included in the study. Patch and photopatch tests, and laboratory tests including serum hormonal evaluation were performed. Skin biopsies were performed on lesional skin and perilesional normal skin. RESULTS: All the patients were women and all were perimenopausal. The lesions were characterized by bilateral, symmetrical, brown-to-grey patchy or mottled pigmentation on the lateral neck. There were positive photopatch results in some cases, but their relevance was doubtful. All laboratory findings were within the normal ranges. The histological findings showed marked accumulation of pigment in the dermis with perivascular lymphocytic infiltration. A significantly higher expression of melanogenesis-associated proteins and an increased number of melanocytes were observed in the epidermis of the lesional skin. The melanin-bearing cells in the dermis were stained with factor XIIIa or CD68, but the majority of these cells were identified as factor XIIIa+ dermal dendrocytes. Some brown pigments were mixed with light brown or golden brown pigment that was positive in iron staining. CONCLUSIONS: These cases seem to represent a continuum of Riehl melanosis. However, the principal distribution of the pigmentation is a distinguishing feature. Any consistent predisposing factors were not established, but there may be a role for subclinical injury or inflammation as possible causative factors for development of the pigmentation. PMID- 22091621 TI - Physiological and perceptual responses to affect-regulated exercise in healthy young women. AB - The purpose of the study was to objectively measure the exercise intensity associated with affective responses of "good" and "fairly good." In Study 1, 8 active females completed 20 min of affect-regulated exercise to feel "good" or "fairly good" (order counterbalanced) followed by an intensity replication session. On-line gas analysis was used during the replication session to measure the physiological cost of exercising. In Study 2, 10 females completed either 3 trials of exercise to feel "good" (n = 5) or 3 trials to feel "fairly good" (n = 5). Each trial consisted of an affect-regulated session followed by a replication session. Across studies, the intensity to feel "fairly good" was significantly higher than to feel "good." Both intensities lay close to ventilatory threshold. The results add to evidence that women can use affect to regulate intensity and exercise at an intensity that would confer fitness and health benefits if maintained. PMID- 22091622 TI - An extension of the functional cerebral systems approach to hostility: a capacity model utilizing a dual concurrent task paradigm. AB - Regulatory control of emotions and expressive fluency (verbal or design) have historically been associated with the frontal lobes. Moreover, research has demonstrated the importance of cerebral laterality with a prominent role of the right frontal regions in the regulation of negative affect (anger, hostility) and in the fluent production of designs rather than verbal fluency. In the present research, participants identified with high and with low levels of hostility were evaluated on a design fluency test twice in one experimental session. Before the second administration of the fluency test, each participant underwent physiological (cold pressor) stress. It was hypothesized that diminished right frontal capacity in high-hostile men would be evident through lowered performance on this cognitive stressor. Convergent validity of the capacity model was supported wherein high-hostile men evidenced reduced delta magnitude over the right frontal region after exposure to the physiological stressor but failed to maintain consistent levels of right cerebral activation across conditions. The results suggest an inability for high-hostile men to maintain stable levels of cerebral activation after exposure to physiological and cognitive stress. Moreover, low-hostiles showed enhanced cognitive performance on the design task with lower levels of arousal (heightened delta magnitude). In contrast, reduced arousal yielded increased executive deficits in high-hostiles as evidenced through increased perseverative errors on the design fluency task. PMID- 22091623 TI - Pharmaceutical price controls and minimum efficacy regulation: evidence from the United States and Italy. AB - OBJECTIVE: This article examines the relationship between drug price and drug quality and how it varies across two of the most common regulatory regimes in the pharmaceutical market: minimum efficacy standards (MES) and a mix of MES and price control mechanisms (MES + PC). DATA SOURCES: Our primary data source is the Tufts-New England Medical Center-Cost Effectiveness Analysis Registry which have been merged with price data taken from MEPS (for the United States) and AIFA (for Italy). STUDY DESIGN: Through a simple model of adverse selection we model the interaction between firms, heterogeneous buyers, and the regulator. PRINCIPAL FINDINGS: The theoretical analysis provides two results. First, an MES regime provides greater incentives to produce high-quality drugs. Second, an MES + PC mix reduces the difference in price between the highest and lowest quality drugs on the market. CONCLUSION: The empirical analysis based on United States and Italian data corroborates these results. PMID- 22091624 TI - Sphingosine kinase-signaling pathway: a possible therapeutic target for post operative cognitive dysfunction. PMID- 22091625 TI - Immunological response to Parthenium hysterophorus in Indian Patients with Parthenium sensitive atopic dermatitis. AB - Parthenium hysterophorus is the leading cause of airborne contact dermatitis, a type IV hypersensitivity reaction in India. Though there are reports of it causing type-I hypersensitivity in atopic individuals in the form of allergic rhinitis and asthma, there is very little information on its role in pathogenesis of atopic dermatitis (AD), another predominately type I hypersensitivity. In the present study, we evaluated the presence of immediate hypersensitivity to P. hysterophorus in patients with AD and evaluated the in vitro immunological response of P. hysterophorus SPT positive AD patients to stimulation with P hysterophorus allergen. In 70 patients (age 15-45 years) with AD and 70 healthy controls, who were patch test negative to P. hysterophorus, immediate hypersensitivity to P hysterophorus was determined by skin prick test (SPT). In SPT positive patients with AD and SPT negative controls, the absolute eosinophil count (AEC), the total serum IgE and Parthenium specific IgE were determined and PBMC proliferation assay to Parthenium pollen using tritiated thymidine incorporation was done. The IL-4, IL-10, IL-2 and IFN-gamma from stimulated PBMCs culture supernatant was also quantified using sandwich ELISA in both groups of patients. Twenty-five (35.7%) of 70 patients with AD had a positive SPT to Parthenium, compared to 3 (4.3%) of controls. The mean AEC, the mean total IgE and Parthenium specific IgE were significantly elevated in SPT positive AD patients vis-a-vis SPT negative controls. Similarly in the Parthenium specific PBMCs proliferation assay, the stimulation index as well as the Th2 cytokine (IL 4 and IL-10) profile were significantly elevated in SPT positive AD patients vis a-vis SPT negative controls but there was no difference in the Th1 cytokine (IL-2 and IFN-gamma) profile. Our study suggests that a third of patients with AD demonstrated a type I hypersensitivity to P. hysterophorus with a Th2 biased cytokine profile (IL-4 and IL-10) in culture supernatant of Parthenium stimulated PBMCs in these patients. PMID- 22091626 TI - A narrower scope or a clearer lens for personality? Examining sources of observers' advantages over self-reports for predicting performance. AB - Emerging studies have shown that observers' ratings of personality predict performance behaviors better than do self-ratings. However, it is unclear whether these predictive advantages stem from (a) use of observers who have a frame of reference more closely aligned with the criterion ("narrower scope") or (b) observers having greater accuracy than targets themselves ("clearer lens"). In a primary study of 291 raters of 97 targets, we found predictive advantages even when observers were personal acquaintances who knew targets only outside of the work context. Integrating these findings with previous meta-analyses showed that colleagues' unique perspectives did not predict incrementally beyond commonly held trait perceptions across all raters (except for openness) and that self raters who overestimate their agreeableness and conscientiousness perform worse on the job. Broadly, our results suggest that observers have clearer lenses for viewing targets' personality traits, and we discuss the theoretical implications of these findings for studying and measuring personality. PMID- 22091627 TI - Nurse staffing and deficiencies in the largest for-profit nursing home chains and chains owned by private equity companies. AB - OBJECTIVE: To compare staffing levels and deficiencies of the 10 largest U.S. for profit nursing home chains with five other ownership groups and chain staffing and deficiencies before and after purchase by four private equity (PE) companies. DATA SOURCES: Facilities for the largest for-profit chains were identified through Internet searches and company reports and matched with federal secondary data for 2003-2008 for each ownership group. STUDY DESIGN: Descriptive statistics and generalized estimation equation panel regression models examined staffing and deficiencies by ownership groups in the 2003-2008 period, controlling for facility characteristics, resident acuity, and market factors with state fixed effects. PRINCIPAL FINDINGS: The top 10 for-profit chains had lower registered nurse and total nurse staffing hours than government facilities, controlling for other factors. The top 10 chains received 36 percent higher deficiencies and 41 percent higher serious deficiencies than government facilities. Other for-profit facilities also had lower staffing and higher deficiencies than government facilities. The chains purchased by PE companies showed little change in staffing levels, but the number of deficiencies and serious deficiencies increased in some postpurchase years compared with the prepurchase period. CONCLUSIONS: There is a need for greater study of large for-profit chains as well as those chains purchased by PE companies. PMID- 22091628 TI - Incidence of serious upper and lower gastrointestinal events in older adults with and without Alzheimer's disease. AB - OBJECTIVES: To estimate and compare the incidence of serious upper and lower gastrointestinal (GI) events in individuals aged 65 and older with and without Alzheimer's disease (AD). DESIGN: Retrospective cohort study. SETTING: PharMetrics, a large population-based health insurance claims database was used for the study. PARTICIPANTS: Individuals aged 65 and older with a diagnosis of AD (International Classification of Diseases, Ninth Revision, Clinical Modification Code 331.0) were identified between January 1, 2003, and December 31, 2006, using the PharMetrics database. The control cohort consisted of a random sample of health plan enrollees matched to the AD cohort according to age, sex, location, and index year in a 1:1 ratio. MEASURES: The outcomes of interest were serious GI events, including ulceration, perforation, and bleeding in the upper or lower GI tract. RESULTS: Twenty-seven thousand seventy-six individuals with AD were identified. Approximately 66% of them were age 80 and older, and 65% were female. Participants with AD had higher incidence of serious GI events (upper GI: AD vs non-AD: 27.4 vs 17.1/1000 person-years, HR = 1.49, 95%CI = 1.34-1.65; lower GI: AD vs non-AD: 9.4 vs 6.9/1000 person-years, HR = 1.26, 95%CI = 1.06-1.48). The association was also present in participants without a history of GI bleeding (upper GI: HR = 1.54, 95%CI = 1.37-1.73; lower GI: HR = 1.37, 95%CI = 1.14-1.64). CONCLUSION: Participants with AD had higher incidence of serious upper and lower GI events, compared to those without AD. Physicians should recognize the high risk of serious GI events that exists in individuals with AD. PMID- 22091629 TI - Use of the PleuralPort device for management of pleural effusion in six dogs and four cats. AB - OBJECTIVE: To describe the placement technique, complications, and outcomes associated with use of the PleuralPort device for management of pleural effusion in dogs and cats. STUDY DESIGN: Case Series. ANIMALS: Six dogs and 4 cats. METHODS: Medical records of all animals with pleural effusion managed with the PleuralPort device were reviewed. Data regarding signalment, fluid analysis, placement technique, duration of function, duration of implantation, complications, and outcome were collected. Owners and referring veterinarians were contacted for follow-up information. RESULTS: Nine animals had chylous effusion and 1 dog had pleural carcinomatosis. Eleven ports were placed with 1 cat receiving bilateral ports. Four animals developed complications. One cat developed pneumothorax immediately after implantation and was euthanatized. In 2 dogs and 1 cat, the ports obstructed. The 6 remaining animals had functioning ports at time of death or resolution of effusion and no longer required use of the port. No significant port migration, irritation, or infection of the device was reported. Excluding the cat with pneumothorax, median duration of port function was 20 days (range 1-391), and median duration of port implantation was 391 days (range 6-723). CONCLUSIONS: The PleuralPort device is a feasible option for the management of pleural effusion in dogs and cats. PMID- 22091630 TI - The identification of frailty: a systematic literature review. AB - An operational definition of frailty is important for clinical care, research, and policy planning. The literature on the clinical definitions, screening tools, and severity measures of frailty were systematically reviewed as part of the Canadian Initiative on Frailty and Aging. Searches of MEDLINE from 1997 to 2009 were conducted, and reference lists of retrieved articles were pearled, to identify articles published in English and French on the identification of frailty in community-dwelling people aged 65 and older. Two independent reviewers extracted descriptive information on study populations, frailty criteria, and outcomes from the selected papers, and quality rankings were assigned. Of 4,334 articles retrieved from the searches and 70 articles retrieved from the pearling, 22 met study inclusion criteria. In the 22 articles, physical function, gait speed, and cognition were the most commonly used identifying components of frailty, and death, disability, and institutionalization were common outcomes. The prevalence of frailty ranged from 5% to 58%. Despite significant work over the past decade, a clear consensus definition of frailty does not emerge from the literature. The definition and outcomes that best suit the unique needs of the researchers, clinicians, or policy-makers conducting the screening determine the choice of a screening tool for frailty. Important areas for further research include whether disability should be considered a component or an outcome of frailty. In addition, the role of cognitive and mood elements in the frailty construct requires further clarification. PMID- 22091631 TI - Fabrication of Au-Pd core-shell heterostructures with systematic shape evolution using octahedral nanocrystal cores and their catalytic activity. AB - By using octahedral gold nanocrystals with sizes of approximately 50 nm as the structure-directing cores for the overgrowth of Pd shells, Au-Pd core-shell heterostructures with systematic shape evolution can be directly synthesized. Core-shell octahedra, truncated octahedra, cuboctahedra, truncated cubes, and concave cubes were produced by progressively decreasing the amount of the gold nanocrystal solution introduced into the reaction mixture containing cetyltrimethylammonium bromide (CTAB), H(2)PdCl(4), and ascorbic acid. The core shell structure and composition of these nanocrystals has been confirmed. Only the concave cubes are bounded by a variety of high-index facets. This may be a manifestation of the release of lattice strain with their thick shells at the corners. Formation of the [CTA](2)[PdBr(4)] complex species has been identified spectroscopically. Time-dependent UV-vis absorption spectra showed faster Pd source consumption rates in the growth of truncated cubes and concave cubes, while a much slower reduction rate was observed in the generation of octahedra. The concave cubes and octahedra were used as catalysts for a Suzuki coupling reaction. They can all serve as effective and recyclable catalysts, but the concave cubes gave higher product yields with a shorter reaction time attributed to their high-index surface facets. The concave cubes can also catalyze a wide range of Suzuki coupling reactions using aryl iodides and arylboronic acids with electron-donating and -withdrawing substituents. PMID- 22091632 TI - Combined E7-dendritic cell-based immunotherapy and human sodium/iodide symporter radioiodine gene therapy with monitoring of antitumor effects by bioluminescent imaging in a mouse model of uterine cervical cancer. AB - Using a uterine cervical cancer cell line expressing human papillomavirus (HPV) 16 E7 antigen and bioluminescent imaging (BLI), we evaluated the therapeutic potential of combined immunotherapy using transfected dendritic cells (DC-E7) and human sodium/iodide symporter (hNIS) radioiodine gene therapy in a xenograft animal cancer model. Dendritic cells expressing either E7 antigen (DC-E7) or no insert (DC-no insert) were made for immunization materials, and murine uterine cervical cancer cell line coexpressing E7, firefly luciferase, hNIS, and EGFP genes (TC-1/FNG) were prepared for the animal tumor model. C57BL/6 mice were divided into five therapy groups (phosphate-buffered saline [PBS], DC-no insert, DC-E7, I-131, and DC-E7+I-131 groups). Single therapy with either DC-E7 or I-131 induced greater retardation in tumor growth compared with PBS or DC-no insert groups, and it resulted in some tumor-free mice (DC-E7 and I-131 groups, 40% and 20%, respectively). Combination therapy with DC-E7 and I-131 dramatically inhibited tumor growth, thus causing complete disappearance of tumors in all mice, and these effects were further confirmed by BLI in vivo. In conclusion, complete disappearance of the tumor was achieved with combined DC-E7 vaccination and hNIS radioiodine gene therapy in a mouse model with E7-expressing uterine cervical cancer, and serial BLIs successfully demonstrated antitumor effects in vivo. PMID- 22091633 TI - Desktop study of occupational exposure judgments: do education and experience influence accuracy? AB - This study examines the impact of several experience and education determinants on exposure judgment accuracy. The study used desktop assessments performed on several different tasks with different exposure profiles to identify correlations between determinants and judgment accuracy using logistic regression models. The exposure judgments were elicited from industrial hygienists with varying levels of experience, education, and training. Videos and written and oral information about the exposure tasks were presented to all participants as they documented a series of qualitative and quantitative exposure judgment probabilities in four exposure categories. Participants (n = 77) first documented their qualitative and then their quantitative exposure assessments after receiving the series of sampling data points. Data interpretation tests and training in simple rules-of thumb for data interpretation were also given to each participant to investigate the impact of data interpretation skills on exposure judgment accuracy. Logistic regression analysis indicated "years of exposure assessment experience" (p < 0.05), "highest EHS degree" (p < 0.05), and a participant's "data interpretation test score" (p < 0.05) directly impacted qualitative exposure judgment accuracy. Logistic regression models of quantitative judgment accuracy showed positive correlation with "greater than 10 years of exposure assessment experience" (p < 0.05), "highest EHS degree" (p < 0.05), a participant's "data interpretation test score" (p < 0.001), rules-of-thumb data interpretation training (p < 0.001), and the number of sample data points available for a judgment (p < 0.005). Analyzing judgments in subsets for participants with less or more than 10 years' experience indicated additional correlations with Certified Industrial Hygienist and Certified Safety Professional certifications, total number of task exposure assessments, and career number of air surveys. The correlation of qualitative and quantitative exposure judgment accuracy with "greater than 10 years experience" supports similar research findings from other fields. The results of this study indicate that several determinants of experience, education, and training, in addition to the availability of sampling data, significantly impact the accuracy of exposure assessments. The findings also suggest methods for enhancing exposure judgment accuracy through statistical tools, mathematical exposure modeling, and specific training. PMID- 22091634 TI - Heat, electricity, or transportation? The optimal use of residual and waste biomass in Europe from an environmental perspective. AB - The optimal use of forest energy wood, industrial wood residues, waste wood, agricultural residues, animal manure, biowaste, and sewage sludge in 2010 and 2030 was assessed for Europe. An energy system model was developed comprising 13 principal fossil technologies for the production of heat, electricity, and transport and 173 bioenergy conversion routes. The net environmental benefits of substituting fossil energy with bioenergy were calculated for all approximately 1500 combinations based on life cycle assessment (LCA) results. An optimization model determines the best use of biomass for different environmental indicators within the quantified EU-27 context of biomass availability and fossil energy utilization. Key factors determining the optimal use of biomass are the conversion efficiencies of bioenergy technologies and the kind and quantity of fossil energy technologies that can be substituted. Provided that heat can be used efficiently, optimizations for different environmental indicators almost always indicate that woody biomass is best used for combined heat and power generation, if coal, oil, or fuel oil based technologies can be substituted. The benefits of its conversion to SNG or ethanol are significantly lower. For non woody biomass electricity generation, transportation, and heating yield almost comparable benefits as long as high conversion efficiencies and optimal substitutions are assured. The shares of fossil heat, electricity, and transportation that could be replaced with bioenergy are also provided. PMID- 22091635 TI - Thermodynamic properties of arsenic compounds and the heat of formation of the As atom from high level electronic structure calculations. AB - Structures, vibrational frequencies, atomization energies at 0 K, and heats of formation at 0 and 298 K are predicted for the compounds As(2), AsH, AsH(2), AsH(3), AsF, AsF(2), and AsF(3) from frozen core coupled cluster theory calculations performed with large correlation consistent basis sets, up through augmented sextuple zeta quality. The coupled cluster calculations involved up through quadruple excitations. For As(2) and the hydrides, it was also possible to examine the impact of full configuration interaction on some of the properties. In addition, adjustments were incorporated to account for extrapolation to the frozen core complete basis set limit, core/valence correlation, scalar relativistic effects, the diagonal Born-Oppenheimer correction, and atomic spin orbit corrections. Based on our best theoretical D(0)(As(2)) and the experimental heat of formation of As(2), we propose a revised 0 K arsenic atomic heat of formation of 68.86 +/- 0.8 kcal/mol. While generally good agreement was found between theory and experiment, the heat of formation of AsF(3) was an exception. Our best estimate is more than 7 kcal/mol more negative than the single available experimental value, which argues for a re-examination of that measurement. PMID- 22091636 TI - Pore development in carbonized hemoglobin by concurrently generated MgO template for activity enhancement as fuel cell cathode catalyst. AB - Various carbon materials with a characteristic morphology and pore structure have been produced using template methods in which a carbon-template composite is once formed and the characteristic features derived from the template are generated after the template removal. In this study, hemoglobin, which is a natural compound that could be abundantly and inexpensively obtained, was used as the carbon material source to produce a carbonaceous noble-metal-free fuel cell cathode catalyst. Magnesium oxide was used as the template concurrently generated with the hemoglobin carbonization from magnesium acetate mixed with hemoglobin as the starting material mixture to enable pore development for improving the activity of the carbonized hemoglobin for the cathodic oxygen reduction. After removal of the MgO template, the substantially developed pores were generated in the carbonized hemoglobin with an amorphous structure observed by total-electron yield X-ray absorption. The extended X-ray absorption fine structure at the Fe-K edge indicated that Fe was coordinated with four nitrogen atoms (Fe-N(4) moiety) in the carbonized hemoglobin. The oxygen reduction activity of the carbonized hemoglobin evaluated using rotating disk electrodes was dependent on the pore structure. The highly developed pores led to an improved activity. PMID- 22091637 TI - A highly reactive mononuclear non-heme manganese(IV)-oxo complex that can activate the strong C-H bonds of alkanes. AB - A mononuclear non-heme manganese(IV)-oxo complex has been synthesized and characterized using various spectroscopic methods. The Mn(IV)-oxo complex shows high reactivity in oxidation reactions, such as C-H bond activation, oxidations of olefins, alcohols, sulfides, and aromatic compounds, and N-dealkylation. In C H bond activation, the Mn(IV)-oxo complex can activate C-H bonds as strong as those in cyclohexane. It is proposed that C-H bond activation by the non-heme Mn(IV)-oxo complex does not occur via an oxygen-rebound mechanism. The electrophilic character of the non-heme Mn(IV)-oxo complex is demonstrated by a large negative rho value of -4.4 in the oxidation of para-substituted thioanisoles. PMID- 22091638 TI - Dissecting the structure, thermodynamic stability, and aggregation properties of the A25T transthyretin (A25T-TTR) variant involved in leptomeningeal amyloidosis: identifying protein partners that co-aggregate during A25T-TTR fibrillogenesis in cerebrospinal fluid. AB - Deposition of amorphous aggregates and fibrils of transthyretin (TTR) in leptomeninges and subarachnoid vessels is a characteristic of leptomeningeal amyloidosis (LA), a currently untreatable cerebral angiopathy. Herein, we report the X-ray structure of the A25T homotetramer of TTR, a natural mutant described in a patient with LA. The structure of A25T-TTR is indistinguishable from that of wild-type TTR (wt-TTR), indicating that the difference in amyloidogenicity between A25T-TTR and wt-TTR cannot be ascribed to gross structural differences. Using pressure-induced dissociation of the tetramer, we show that A25T-TTR is 3 kcal/mol less stable than L55P-TTR, the most aggressive mutant of TTR described to date. After incubation for 15 days at 37 degrees C (pH 7.3), A25T-TTR forms mature amyloid fibrils. To mimic the environment in which TTR aggregates, we investigated aggregation in cerebrospinal fluid (CSF). Unlike L55P-TTR, A25T-TTR rapidly forms amyloid aggregates in CSF that incorporated several protein partners. Utilizing a proteomics methodology, we identified 19 proteins that copurified with A25T-TTR amyloid fibrils. We confirmed the presence of proteins previously identified to be associated with TTR aggregates in biopsies of TTR amyloidosis patients, such as clusterin, apolipoprotein E, and complement proteins. Moreover, we identified novel proteins, such as blood coagulation proteins. Overall, our results revealed the in vitro characterization of TTR aggregation in a biologically relevant environment, opening new avenues of investigation into the molecular mechanisms of LA. PMID- 22091639 TI - On the resistance to extinction of fear conditioned to angry faces. AB - The present study investigated whether, like fear conditioned to pictures of snakes and spiders, fear conditioned to angry faces resists extinction even after verbal instruction and removal of the shock electrode. Participants were trained in a differential Pavlovian fear conditioning procedure with angry face or happy face conditional stimuli (CSs). Prior to extinction, half the participants in each group were informed that no more unconditional stimuli would be presented and the shock electrode was removed. In the absence of this manipulation, participants showed resistance to extinction after training with angry face CSs, but not after training with happy face CSs. Instructed extinction and electrode removal abolished fear conditioning regardless of the emotion expressed by the CS faces. This finding suggests that fear conditioned to angry faces, like fear conditioned to racial out-group faces, is more malleable than fear conditioned to snakes and spiders. PMID- 22091640 TI - Estimating changes in public health following implementation of hazard analysis and critical control point in the United States broiler slaughter industry. AB - A common approach to reducing microbial contamination has been the implementation of a Hazard Analysis and Critical Control Point (HACCP) program to prevent or reduce contamination during production. One example is the Pathogen Reduction HACCP program implemented by the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS). This program consisted of a staged implementation between 1996 and 2000 to reduce microbial contamination on meat and poultry products. Of the commodities regulated by FSIS, one of the largest observed reductions was for Salmonella contamination on broiler chicken carcasses. Nevertheless, how this reduction might have influenced the total number of salmonellosis cases in the United States has not been assessed. This study incorporates information from public health surveillance and surveys of the poultry slaughter industry into a model that estimates the number of broiler related salmonellosis cases through time. The model estimates that-following the 56% reduction in the proportion of contaminated broiler carcasses observed between 1995 and 2000-approximately 190,000 fewer annual salmonellosis cases (attributed to broilers) occurred in 2000 compared with 1995. The uncertainty bounds for this estimate range from approximately 37,000 to 500,000 illnesses. Estimated illnesses prevented, due to the more modest reduction in contamination of 13% between 2000 and 2007, were not statistically significant. An analysis relating the necessary magnitude of change in contamination required for detection via human surveillance also is provided. PMID- 22091641 TI - The characterization and comparison of Staphylococcus aureus by antibiotic susceptibility testing, enterobacterial repetitive intergenic consensus polymerase chain reaction, and random amplified polymorphic DNA-polymerase chain reaction. AB - Thirty-five of Staphylococcus aureus isolated from food raw materials and workers' hands in a noshery were characterized using antibiotic susceptibility testing, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), and random amplified polymorphic DNA (RAPD)-PCR. As a similarity threshold of 90%, ERIC-PCR classified 35 S. aureus isolates into 28 ERIC types with discrimination indexes (D) of 0.984, while RAPD-PCR grouped 35 S. aureus isolates into five clusters (A-E) showing 19 RAPD types with D of 0.949. Four resistance patterns were observed with D of 0.826. A comparison of characterization of S. aureus indicated a clear correlation between ERIC-PCR and RAPD-PCR or resistance patterns in some strains. It was concluded that ERIC-PCR method could be used for genetic diversity of S. aureus and tracing the sources of it from the food chain. PMID- 22091642 TI - Methodology of photic stimulation revisited: updated European algorithm for visual stimulation in the EEG laboratory. AB - Intermittent photic stimulation (IPS) is a common procedure performed in the electroencephalography (EEG) laboratory in children and adults to detect abnormal epileptogenic sensitivity to flickering light (i.e., photosensitivity). In practice, substantial variability in outcome is anecdotally found due to the many different methods used per laboratory and country. We believe that standardization of procedure, based on scientific and clinical data, should permit reproducible identification and quantification of photosensitivity. We hope that the use of our new algorithm will help in standardizing the IPS procedure, which in turn may more clearly identify and assist monitoring of patients with epilepsy and photosensitivity. Our algorithm goes far beyond that published in 1999 (Epilepsia, 1999a, 40, 75; Neurophysiol Clin, 1999b, 29, 318): it has substantially increased content, detailing technical and logistical aspects of IPS testing and the rationale for many of the steps in the IPS procedure. Furthermore, our latest algorithm incorporates the consensus of repeated scientific meetings of European experts in this field over a period of 6 years with feedback from general neurologists and epileptologists to improve its validity and utility. Accordingly, our European group has provided herein updated algorithms for two different levels of methodology: (1) requirements for defining photosensitivity in patients and in family members of known photosensitive patients and (2) requirements for tailored studies in patients with a clear history of visually induced seizures or complaints, and in those already known to be photosensitive. PMID- 22091645 TI - Time-course effects of St John's wort on the pharmacokinetics of cyclosporine in dogs: interactions between herbal extracts and drugs. AB - To clarify the interaction between St John's wort (SJW) and cyclosporine (CsA) in dogs, the pharmacokinetics of CsA before and during the repeated administration of SJW were analyzed. In the SJW group, SJW (300 mg) was given orally to four dogs every 24 h for 14 days. A single dose of CsA (5 mg/kg) was given orally 7 days before and 7 and 14 days after the initiation of the repeated administration of SJW. In the Control group, a single dose of CsA (5 mg/kg) was given orally to four other dogs in accordance with that in the SJW group. Blood samples from both groups were collected, and whole-blood concentrations of CsA were determined using high-performance liquid chromatography with UV detection. The maximum whole blood concentration and AUC(0-infinity) of the SJW group were significantly lower and the CL(tot) /F and V(d) /F were significantly higher than those in the Control group 7 and 14 days after the initiation of repeated SJW. Thus, repeated administrations of SJW affect the pharmacokinetic profiles of CsA in dogs. Further studies are necessary to elucidate the mechanisms of interaction between SJW and CsA in dogs. PMID- 22091646 TI - Virus hazards from food, water and other contaminated environments. AB - Numerous viruses of human or animal origin can spread in the environment and infect people via water and food, mostly through ingestion and occasionally through skin contact. These viruses are released into the environment by various routes including water run-offs and aerosols. Furthermore, zoonotic viruses may infect humans exposed to contaminated surface waters. Foodstuffs of animal origin can be contaminated, and their consumption may cause human infection if the viruses are not inactivated during food processing. Molecular epidemiology and surveillance of environmental samples are necessary to elucidate the public health hazards associated with exposure to environmental viruses. Whereas monitoring of viral nucleic acids by PCR methods is relatively straightforward and well documented, detection of infectious virus particles is technically more demanding and not always possible (e.g. human norovirus or hepatitis E virus). The human pathogenic viruses that are most relevant in this context are nonenveloped and belong to the families of the Caliciviridae, Adenoviridae, Hepeviridae, Picornaviridae and Reoviridae. Sampling methods and strategies, first-choice detection methods and evaluation criteria are reviewed. PMID- 22091649 TI - Infant mortality and fertility in three Bavarian villages: An analysis of family histories from the 19th century. AB - Abstract Family history data derived from the records of three parishes in Bavaria provide evidence for several important demographic questions when analysed in conjunction with information concerning the prevalent breast-feeding practices. The results suggest strongly that breast feeding can prolong birth intervals substantially. The evidence concerning the independent influence of infant deaths on subsequent birth intervals is inconclusive. It is clear, however, that even if such an influence did exist it was relatively small, compared to the effect of lactation. In addition the results do not lend support to the hypothesis that couples experiencing low child mortality practised family limitation more than couples experiencing high child mortality. In all three parishes, however, fertility appeared to influence infant mortality. Infants born after short intervals were subject to considerably higher mortality risks than infants following longer intervals. PMID- 22091650 TI - Birth control and regional differentials in the Soviet Union. AB - Abstract Following the territorial division pointed out by Urlanis into those parts of the Soviet Union where birth control is practised and where it is not as widespread, it is possible to ascertain the importance of different factors bearing on fertility within each region. This study was based on data obtained from the 1959 USSR Census of Population including information on social and demographic characteristics of the urban and rural populations for over 150 political-administrative areas. In Central Asia, Azerbaidjan and Armenia, outside the region of birth control, the level of fertility depends mainly on the proportion of women who are married and also on their social position measured by the discrepancy in the educational status of men and women. In contrast, the birth control region of a relatively low level of fertility in urban areas, for example, displays the characteristic of women's educational achievement most strongly associated with the child-woman ratio. Except for the rural areas in this region, the present study fails to support the popular hypothesis that economic dependency of women is directly related to fertility. PMID- 22091651 TI - Altitude, fertility and mortality in Andean countries. AB - Abstract Using the census data for Peru, Bolivia and Ecuador, previous writers have investigated some possible determinants of inter-regional differences in fertility; language spoken, female participation rates, and altitude. This paper points out the many sources of inaccuracy in the census data used. It argues that the indicators of unusually low fertility in the highland, predominantly Indianspeaking areas fail to control effectively for the very high levels of infant mortality in these regions. Fragmentary survey results give some indication of the scale of infant mortality, and appear to refute the idea that fertility is exceptionally low in areas of high altitude. In an attempt to explain why such high mortality rates persist in the Andean region the main health problems of Bolivia are examined. It seems that the causes are economic and social, rather than physiological. Unfortunately a change of policy which reduced death rates would produce grave new social problems. PMID- 22091652 TI - A study on the demographic impact of an IUD programme. AB - Abstract This paper discusses and presents data obtained through various studies and surveys on the effect of the IUD contraceptive programme in Taiwan. It has been demonstrated that the fertility of IUD acceptors before first acceptance was 58 % higher than that of married women in general and that, after acceptance, it declined by about 76%. The corresponding fertility decline among married women in general was only about %. Acceptors had had more recent births, as indicated by their shorter 'open interval' of 20.7 months, compared with 374 months among the women in the KAP survey sample. If the fertility of IUD acceptors had declined at the same rate as that of married women in general in the absence of IUD, the insertion of about 4 IUDs would probably prevent one live birth in the following year. Observation over a longer period, however, is needed to determine the demographic effect of IUD. Data on fertility control practice after termination, type of termination of pregnancies after first acceptance, life-table rates by various socio-demographic characteristics of acceptors, and the 'life expectancy' of the first segment of IUD are also presented. PMID- 22091653 TI - Determinants of rural-urban migration in Ghana. AB - Abstract In the 39 years between the 1921 and 1960 censuses, urban population in Ghana multiplied by nine while the population of the whole country only trebled. The major factor in urban growth was rural-urban migration and the reproduction of the migrants. In 1963 a survey consisting of a systematic sample of households in 45 rural centres, randomly chosen in Local Authority Areas selected in accord with the regional rural population distribution, reconstituted the rural population so as to include current migrants in the towns as well as those remaining in rural areas. For analysis 13,748 respondents were divided into 14 categories by ruralurban migration behaviour. At the same time a survey of urban population provided a check on rural-urban migration data. study of the propensity to migrate from rural to urban areas shows that this increases with the closeness of the rural area to a large town, the population size of the rural centre, the economic well-being of the rural household, the number of relatives already in the urban area, the individual's level of education, larger family size and probably lower birth rank, as well as exhibiting specific age and sex patterns. It is shown that only a minor role is played by occupation, conjugal condition and number of dependants. Various interrelations between these factors are discussed, and attention is given to the special importance of education in partially or wholly determining some of the other factors. Census data are used to demonstrate the effect of rural-urban migration in concentrating persons with certain characteristics in the urban areas. PMID- 22091654 TI - Reflections on the demographic conditions needed to establish a U.S. stationary population growth. AB - Abstract It is assumed that in the long run U.S. population growth will have to cease, as otherwise life will become physically impossible. Various hypothetical possibilities of achieving such a type of development are investigated. Alternatives of reproduction rate trends are considered in terms of alternatives of interactions of assumed age-specific fertility and mortality trends and these are computed and evaluated. The various computations then indicate the nature of childbearing attitudes and behaviour, which the 'average population' would have to adopt in order to achieve the desired stationary population growth after a certain period of time. On the other hand the results presented in the paper also indicate that a certain population growth (of the order of 30-50%) and change in age structure is inevitable in the coming 5-10 decades given the initial childbearing behaviour. PMID- 22091655 TI - Observations on the relationship between frequency and timing of intercourse and the probability of conception. AB - Abstract Several aspects of stochastic models as they relate to the monthly probability of conception are explored. In particular a method of obtaining the required probability distributions proceeding from a rather general description of human behaviour is presented. The number of acts of intercourse per month is considered as a random variable rather than being taken as a fixed constant. The pattern of intercourse is characterized mathematically. The construction of the probability function is presented and illustrated numerically. he Weibull distribution is shown to illustrate considerable flexibility in describing these differing patterns of intercourse quantitatively. The resulting probabilities of conception vary considerably under changing parameter values even when the expected number of acts of intercourse is taken to be nearly equal. The relevance of these considerations is discussed. PMID- 22091656 TI - The Mathematics of the menstrual cycle. AB - Abstract Attempts have been made to rebut criticisms by Professor Potter of a rhythm method of contraception described by the author. There is a correlation between the lengths of adjacent cycles within the menstrual histories of some women. PMID- 22091659 TI - Eltrombopag named patient programme for patients with chronic immune thrombocytopenia. PMID- 22091662 TI - Kernel current source density method. AB - Local field potentials (LFP), the low-frequency part of extracellular electrical recordings, are a measure of the neural activity reflecting dendritic processing of synaptic inputs to neuronal populations. To localize synaptic dynamics, it is convenient, whenever possible, to estimate the density of transmembrane current sources (CSD) generating the LFP. In this work, we propose a new framework, the kernel current source density method (kCSD), for nonparametric estimation of CSD from LFP recorded from arbitrarily distributed electrodes using kernel methods. We test specific implementations of this framework on model data measured with one-, two-, and three-dimensional multielectrode setups. We compare these methods with the traditional approach through numerical approximation of the Laplacian and with the recently developed inverse current source density methods (iCSD). We show that iCSD is a special case of kCSD. The proposed method opens up new experimental possibilities for CSD analysis from existing or new recordings on arbitrarily distributed electrodes (not necessarily on a grid), which can be obtained in extracellular recordings of single unit activity with multiple electrodes. PMID- 22091663 TI - Quantifying statistical interdependence, part III: N > 2 point processes. AB - Stochastic event synchrony (SES) is a recently proposed family of similarity measures. First, "events" are extracted from the given signals; next, one tries to align events across the different time series. The better the alignment, the more similar the N time series are considered to be. The similarity measures quantify the reliability of the events (the fraction of "nonaligned" events) and the timing precision. So far, SES has been developed for pairs of one-dimensional (Part I) and multidimensional (Part II) point processes. In this letter (Part III), SES is extended from pairs of signals to N > 2 signals. The alignment and SES parameters are again determined through statistical inference, more specifically, by alternating two steps: (1) estimating the SES parameters from a given alignment and (2), with the resulting estimates, refining the alignment. The SES parameters are computed by maximum a posteriori (MAP) estimation (step 1), in analogy to the pairwise case. The alignment (step 2) is solved by linear integer programming. In order to test the robustness and reliability of the proposed N-variate SES method, it is first applied to synthetic data. We show that N-variate SES results in more reliable estimates than bivariate SES. Next N variate SES is applied to two problems in neuroscience: to quantify the firing reliability of Morris-Lecar neurons and to detect anomalies in EEG synchrony of patients with mild cognitive impairment. Those problems were also considered in Parts I and II, respectively. In both cases, the N-variate SES approach yields a more detailed analysis. PMID- 22091661 TI - Response activation impairments in schizophrenia: evidence from the lateralized readiness potential. AB - Previous research has demonstrated deficits in preresponse motor activity in schizophrenia, as evidenced by a reduced lateralized readiness potential (LRP). The LRP deficit could be due to increased activation of the incorrect response (e.g., failure to suppress competition) or to reduced activation of the correct response (e.g., a low-level impairment in response preparation). To distinguish these possibilities, we asked whether the LRP impairment is increased under conditions of strong response competition. We manipulated the compatibility of stimulus-response mappings (Experiment 1) and the compatibility of the target with flankers (Experiment 2). In both experiments, the patient LRP was reduced as much under conditions of low response competition as under high competition. These results are incompatible with a failure of patients to suppress competition and are instead consistent with a deficit in activating the correct response. PMID- 22091664 TI - Noise tolerance of attractor and feedforward memory models. AB - In short-term memory networks, transient stimuli are represented by patterns of neural activity that persist long after stimulus offset. Here, we compare the performance of two prominent classes of memory networks, feedback-based attractor networks and feedforward networks, in conveying information about the amplitude of a briefly presented stimulus in the presence of gaussian noise. Using Fisher information as a metric of memory performance, we find that the optimal form of network architecture depends strongly on assumptions about the forms of nonlinearities in the network. For purely linear networks, we find that feedforward networks outperform attractor networks because noise is continually removed from feedforward networks when signals exit the network; as a result, feedforward networks can amplify signals they receive faster than noise accumulates over time. By contrast, attractor networks must operate in a signal attenuating regime to avoid the buildup of noise. However, if the amplification of signals is limited by a finite dynamic range of neuronal responses or if noise is reset at the time of signal arrival, as suggested by recent experiments, we find that attractor networks can outperform feedforward ones. Under a simple model in which neurons have a finite dynamic range, we find that the optimal attractor networks are forgetful if there is no mechanism for noise reduction with signal arrival but nonforgetful (perfect integrators) in the presence of a strong reset mechanism. Furthermore, we find that the maximal Fisher information for the feedforward and attractor networks exhibits power law decay as a function of time and scales linearly with the number of neurons. These results highlight prominent factors that lead to trade-offs in the memory performance of networks with different architectures and constraints, and suggest conditions under which attractor or feedforward networks may be best suited to storing information about previous stimuli. PMID- 22091666 TI - Nondegenerate piecewise linear systems: a finite Newton algorithm and applications in machine learning. AB - We investigate Newton-type optimization methods for solving piecewise linear systems (PLSs) with nondegenerate coefficient matrix. Such systems arise, for example, from the numerical solution of linear complementarity problem, which is useful to model several learning and optimization problems. In this letter, we propose an effective damped Newton method, PLS-DN, to find the exact (up to machine precision) solution of nondegenerate PLSs. PLS-DN exhibits provable semiiterative property, that is, the algorithm converges globally to the exact solution in a finite number of iterations. The rate of convergence is shown to be at least linear before termination. We emphasize the applications of our method in modeling, from a novel perspective of PLSs, some statistical learning problems such as box-constrained least squares, elitist Lasso (Kowalski & Torreesani, 2008), and support vector machines (Cortes & Vapnik, 1995). Numerical results on synthetic and benchmark data sets are presented to demonstrate the effectiveness and efficiency of PLS-DN on these problems. PMID- 22091667 TI - Intrinsic adaptation in autonomous recurrent neural networks. AB - A massively recurrent neural network responds on one side to input stimuli and is autonomously active, on the other side, in the absence of sensory inputs. Stimuli and information processing depend crucially on the quality of the autonomous state dynamics of the ongoing neural activity. This default neural activity may be dynamically structured in time and space, showing regular, synchronized, bursting, or chaotic activity patterns. We study the influence of nonsynaptic plasticity on the default dynamical state of recurrent neural networks. The nonsynaptic adaption considered acts on intrinsic neural parameters, such as the threshold and the gain, and is driven by the optimization of the information entropy. We observe, in the presence of the intrinsic adaptation processes, three distinct and globally attracting dynamical regimes: a regular synchronized, an overall chaotic, and an intermittent bursting regime. The intermittent bursting regime is characterized by intervals of regular flows, which are quite insensitive to external stimuli, interceded by chaotic bursts that respond sensitively to input signals. We discuss these findings in the context of self organized information processing and critical brain dynamics. PMID- 22091668 TI - Simple modification of Oja rule limits L1-norm of weight vector and leads to sparse connectivity. AB - This letter describes a simple modification of the Oja learning rule, which asymptotically constrains the L1-norm of an input weight vector instead of the L2 norm as in the original rule. This constraining is local as opposed to commonly used instant normalizations, which require the knowledge of all input weights of a neuron to update each one of them individually. The proposed rule converges to a weight vector that is sparser (has more zero weights) than the vector learned by the original Oja rule with or without the zero bound, which could explain the developmental synaptic pruning. PMID- 22091669 TI - Computational advantages of reverberating loops for sensorimotor learning. AB - When we learn something new, our brain may store the information in synapses or in reverberating loops of electrical activity, but current theories of motor learning focus almost entirely on the synapses. Here we show that loops could also play a role and would bring advantages: loop-based algorithms can learn complex control tasks faster, with exponentially fewer neurons, and avoid the problem of weight transport. They do all this at a cost: in the presence of long feedback delays, loop algorithms cannot control very fast movements, but in this case, loop and synaptic mechanisms can complement each other-mixed systems quickly learn to make accurate but not very fast motions and then gradually speed up. Loop algorithms explain aspects of consolidation, the role of attention, and the relapses that are sometimes seen after a task has apparently been learned, and they make further predictions. PMID- 22091670 TI - Spiking neural P systems with astrocytes. AB - In a biological nervous system, astrocytes play an important role in the functioning and interaction of neurons, and astrocytes have excitatory and inhibitory influence on synapses. In this work, with this biological inspiration, a class of computation devices that consist of neurons and astrocytes is introduced, called spiking neural P systems with astrocytes (SNPA systems). The computation power of SNPA systems is investigated. It is proved that SNPA systems with simple neurons (all neurons have the same rule, one per neuron, of a very simple form) are Turing universal in both generative and accepting modes. If a bound is given on the number of spikes present in any neuron along a computation, then the computation power of SNPA systems is diminished. In this case, a characterization of semilinear sets of numbers is obtained. PMID- 22091671 TI - Noninvertibility, chaotic coding, and chaotic multiplexity of synaptically modulated neural firing. AB - Widely accepted neural firing and synaptic potentiation rules specify a cross dependence of the two processes, which, evolving on different timescales, have been separated for analytic purposes, concealing essential dynamics. Here, the morphology of the firing rates process, modulated by synaptic potentiation, is shown to be described by a discrete iteration map in the form of a thresholded polynomial. Given initial synaptic weights, a firing activity is triggered by conductance. Elementary dynamic modes are defined by fixed points, cycles, and saddles of the map, building blocks of the underlying firing code. Showing parameter-dependent multiplicity of real polynomial roots, the map is proved to be noninvertible. The incidence of chaos is then implied by the parameter dependent existence of snap-back repellers. The highly patterned geometric and statistical structures of the associated chaotic attractors suggest that these attractors are an integral part of the neural code. It further suggests the chaotic attractor as a natural mechanism for statistical encoding and temporal multiplexing of neural information. The analytic findings are supported by simulation. PMID- 22091672 TI - European long-term care programs: lessons for community living assistance services and supports? AB - OBJECTIVE: To uncover lessons from abroad for Community Living Assistance Services and Supports (CLASS), a federally run voluntary public long-term care (LTC) insurance program created under the Accountable Care Act of 2010. DATA SOURCES: Program administrators and policy researchers from Austria, England, France, Germany, and the Netherlands. STUDY DESIGN: Qualitative methods focused on key parameters of cash for care: how programs set benefit levels; project expenditures; control administrative costs; regulate the use of benefits; and protect workers. DATA COLLECTION/EXTRACTION METHODS: Structured discussions were conducted during an international conference of LTC experts, followed by personal meetings and individual correspondence. PRINCIPAL FINDINGS: Germany's self financing mandate and tight targeting of benefits have resulted in a solvent program with low premiums. Black markets for care are likely in the absence of regulation; France addresses this via a unique system ensuing legal payment of workers. CONCLUSIONS: Programs in the five countries studied have lessons, both positive and negative, relevant to CLASS design. PMID- 22091673 TI - IgE antibody detection in the diagnosis of hypersensitivity to neuromuscular blocking agents. PMID- 22091674 TI - Imaging of T cells expressing chimeric antigen receptors. PMID- 22091675 TI - Reprogramming intestinal immunity is the answer to induced pathogenic inflammation. PMID- 22091676 TI - Acute graft-versus-host disease. PMID- 22091678 TI - MKP-1 signaling translates innate signals into adaptive responses. PMID- 22091679 TI - Mycophenolate mofetil for the induction and maintenance treatment of lupus nephritis. AB - Mycophenolate mofetil (MMF) inhibits purine synthesis by inhibiting inosine-5' monophosphate dehydrogenase. Since 1995, it has been approved in the USA for the prevention of allograft rejection in solid organ transplant patients. In the last two decades, it has been frequently used as an immunosuppressive therapy for numerous autoimmune conditions including lupus nephritis. Management of lupus nephritis has been advanced by well-designed randomized clinical trials establishing MMF as a viable alternative to established therapies such as pulse intravenous cyclophosphamide in selected patients. This article outlines the pharmacologic properties of MMF and summarizes recent randomized clinical trials in lupus nephritis. PMID- 22091680 TI - Optimizing tumor-targeting chimeric antigen receptor T cells in B-cell lymphoma patients. AB - Evaluation of: Savoldo B, Ramos CA, Liu E et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J. Clin. Invest. 121(5), 1822-1826 (2011). Chimeric antigen receptor (CAR)-T cells are promising antitumor immunotherapies. However, there are limited reports of persistence, tumor-homing and clinical efficacy in cancer patients. Savoldo and colleagues used a novel approach to compare the use of first- and second-generation tumor-specific CAR-T cells in six B-cell lymphoma patients. They provide one of the first comparisons in human subjects and demonstrate the superiority of second-generation CAR-T cells to expand, survive and home to the tumor site. PMID- 22091682 TI - Novel therapies in melanoma. AB - The incidence of cutaneous melanoma is on the rise worldwide despite increasing awareness and vigilance towards prevention by the lay public and health professionals. Melanoma is easily curable by surgical excision when detected early, but it is nearly incurable when discovered in its later stages owing to resistance to treatment. Unfortunately, treatment options traditionally used in melanoma have not shown a survival benefit. However, as the understanding of tumor biology and metastatic growth evolves, new therapeutic options for metastatic melanoma have shown impressive survival benefit. The blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) by use of the monoclonal antibody, ipilimumab (YervoyTM, Bristol-Myers Squibb), produces favorable antitumor immune system responses and was recently approved by the US FDA for use in patients with advanced melanoma. In addition, targeting components of the MAPK pathway have also demonstrated survival advantage in patients with BRAF-mutated melanoma and vemurafenib (ZelborafTM, Plexxikon/Roche) was approved by the FDA in August 2011 for the first-line treatment of both metastatic and unresectable melanomas for patients whose tumors have V600E mutations in the BRAF gene. PMID- 22091681 TI - Use of allogeneic NK cells for cancer immunotherapy. AB - Controversy exists as to the role that the immune system plays in cancer therapy. While the immune system has been proposed to scavenge the body to prevent microscopic transformation from forming cancer, it has been difficult to mount its potential of shrinking established tumors. NK cells are components of the innate immune system. They can recognize targets without prior sensitization, making them ideal candidates to manipulate for therapeutic use against cancer. Initially, autologous NK cells were directed against tumors but it was realized that NK cells that recognize self cells are inhibited. More encouraging advances have been made with allogeneic NK cell therapy in clinical trials to overcome this limitation. In this article, we present developments in NK cell adoptive immunotherapy for hematologic and solid tumor malignancies. PMID- 22091684 TI - Sirolimus in solid organ transplantation: current therapies and new frontiers. AB - Sirolimus (SRL) is a mammalian target of rapamycin inhibitor, which provides an immunosuppressive effect by inhibiting cell cycle progression. The encouraging results of combined SRL-cyclosporine therapy paved the way to further immunosuppressant combinations. Although SRL is relatively non-nephrotoxic when administered as monotherapy, it pharmacodynamically enhances the toxicity of calcineurin inhibitors. Other side effects may include hyperlipidemia and myelosuppression and less commonly wound healing impairment, proteinuria, edema and pneumonitis. Surprisingly, SRL also showed encouraging properties as an antiatherogenic and antineoplastic, opening a large spectrum of new potential applications. Whether SRL can be used safely over the long term with low doses of calcineurin inhibitors requires further study. The use of SRL as a corticosteroid sparing agent also remains to be proven in controlled trials. PMID- 22091683 TI - Stromal cell-based immunotherapy in transplantation. AB - Organs are composed of parenchymal cells that characterize organ function and nonparenchymal cells that are composed of cells in transit, as well as tissue connective tissue, also referred to as tissue stromal cells. It was originally thought that these tissue stromal cells provided only structural and functional support for parenchymal cells and were relatively inert. However, we have come to realize that tissue stromal cells, not restricted to in the thymus and lymphoid organs, also play an active role in modulating the immune system and its response to antigens. The recognition of these elements and the elucidation of their mechanisms of action have provided valuable insight into peripheral immune regulation. Extrapolation of these principles may allow us to utilize their potential for clinical application. In this article, we will summarize a number of tissue stromal elements/cell types that have been shown to induce hyporesponsiveness to transplants. We will also discuss the mechanisms by which these stromal cells create a tolerogenic environment, which in turn results in long-term allograft survival. PMID- 22091685 TI - Developing immunologic tolerance for transplantation at the fetal stage. AB - Given the shortage of human organs for transplantation, the waiting lists are increasing annually and consequently so is the time and deaths during the wait. As most immune suppression therapy is not antigen specific and the risk of infection tends to increase, scientists are looking for new options for immunosuppression or immunotolerance. Tolerance induction would avoid the complications caused by immunosupressive drugs. As such, taking into account the experience with autoimmune diseases, one strategy could be immune modulation induced changes in T-cell cytokine secretion or antigen therapy; however, most clinical trials have failed. Gene transfer of MHC genes across species may be used to induce tolerance to xenogenic solid organs. Other options are induction of central tolerance by the establishment of mixed chimerism through hematopoietic stem cell transplantation and the induction of 'operational tolerance' through immunodeviation involving dendritic or Tregs. I propose that, as the recognition and tolerance of proteins takes place in the thymus, this organ should be the main target for immunotolerance research protocols even as early as during the fetal development. PMID- 22091687 TI - Is low anxiety part of the psychopathy construct? AB - Low anxiety has traditionally been considered a feature of psychopathy, but there has been mixed research support for this conceptualization. We investigated the PPI-R-SF Stress Immunity subscale (a measure of low anxiety) in relation to 2 widely used self-report psychopathy scales in a sample of 346 undergraduate students. Results indicated that PPI-R-SF Stress Immunity was nearly unrelated to other indicators of psychopathy, showing a near-zero loading on the common psychopathy factor defined jointly by the scales of the PPI-R-SF and SRP-III. Stress Immunity also showed a pattern of personality and temperament correlates much different from those of other psychopathy subscales. Finally, Stress Immunity had a slight negative correlation with self-reports of diverse antisocial acts. These results suggest that despite its historical importance in the conceptualization of psychopathy, low anxiety is likely not a core feature of psychopathy. PMID- 22091688 TI - Differences in well-being between GPs, medical specialists, and private physicians: the role of psychosocial factors. AB - OBJECTIVE: To examine the well-being differences among physicians working in different health care sectors and to test whether psychosocial stressors account for these differences. The well-being indicators used were psychological distress, self-rated health, and work ability. DATA SOURCES/STUDY SETTING: A total of 2,841 randomly selected Finnish physicians (response rate 57 percent) returned the postal questionnaire, of which 2,047 (1,241 women) fulfilled all the participant criteria. STUDY DESIGN: This is a cross-sectional questionnaire study. PRINCIPAL FINDINGS: General practitioners and medical specialists experienced lower well-being than private physicians and this difference was partly explained by differences in psychosocial stressors. CONCLUSIONS: General practitioners and medical specialists report more problems in well-being than private physicians. It is of particular importance to be aware of the sector specific difficulties in work environments. PMID- 22091689 TI - Predicting nursing home adherence to a clinical trial intervention: lessons for the conduct of cluster randomized trials. AB - OBJECTIVES: To describe factors predictive of nursing home (NH) adherence to a clinical trial intervention. DESIGN: Post hoc analysis of a cluster randomized trial (CRT) evaluating a structured communication intervention to improve nurse physician telephone communication in NHs. SETTING: NH. PARTICIPANTS: All eligible licensed nursing staff in all participating NHs. MEASUREMENTS: Adherence was defined as active participation for at least 3 months of the 12-month trial. NH characteristics hypothesized to affect trial outcomes (profit status, bed size, nursing staff time, NH quality, and leadership turnover) were measured a priori. The association between intervention adherence, NH characteristics and preintervention questionnaire response rate was examined. RESULTS: Of 13 intervention NHs, seven adhered to the intervention. Three factors differentiated adherent from nonadherent NHs: director of nursing turnover (nonadherent NHs 50% vs adherent NHs 0%, P = .03); Centers for Medicare and Medicaid Services (CMS) nurse staffing rating (range: 1-5) (nonadherent NHs mean 3.7 +/- 0.5 vs adherent NHs mean 4.3 +/- 0.5), P = .048); and questionnaire response rate (nonadherent NHs 15.6 +/- 10.0% vs adherent NHs 34.2 +/- 12.1%, P = .02). Profit status, bed size, and number of NH deficiencies on state surveys were not significantly associated with intervention adherence. CONCLUSION: CMS nurse staffing rating, leadership turnover, and questionnaire response rate are associated with adherence to a CRT intervention. Pretrial evaluation of NH staffing rating by CMS and of response to a questionnaire can help investigators improve trial efficiency by screening for NHs likely to adhere to a CRT intervention. PMID- 22091690 TI - Prospective comparison of cisterna chyli ablation to pericardectomy for treatment of spontaneously occurring idiopathic chylothorax in the dog. AB - OBJECTIVE: Prospective comparison of cisterna chyli ablation (CCA) or pericardectomy (PC) for chylothorax. STUDY DESIGN: Randomized prospective study. SUBJECT POPULATION: Dogs with idiopathic chylothorax (n= 23). METHODS: Dogs were treated by thoracic duct ligation (TDL) with either CCA (n = 12) or PC (n = 11). Long-term outcomes, intraoperative central venous pressures (CVPs) and pericardial histology were assessed. Dogs with persistent chylothorax were offered retreatment by the alternative procedure. RESULTS: Ten (83%) dogs treated by CCA-TDL and 6 (60%) treated by PC-TDL resolved their chylothorax. Retreatment in 4 dogs resulted in resolution in 2 dogs and 2 perioperative deaths. Four dogs developed nonchylous effusions; 2 of which resolved after initiating steroid therapy, 1 of which was unsuccessfully treated by PC, and 1 continues to be managed by thoracocentesis 6.5 years later. CVPs were normal in most dogs and unaffected by PC. On histology, pericardial tissues had extensive external surface fibrosis with mild inflammation. On follow-up (<= 6.5 years), no recurrence of pleural effusions occurred after initial resolution. CONCLUSIONS: CCA-TDL appears to offer improved outcomes over historical results with TDL. Results with PC-TDL were more variable for unknown reasons. Venous pressure measurements did not support the hypothesis that venous hypertension was involved in chylothorax or response to therapy in these dogs. PMID- 22091691 TI - Target family-directed exploration of scaffolds with different SAR profiles. AB - The scaffold concept is widely applied in chemoinformatics and medicinal chemistry to organize bioactive compounds according to common core structures or associate compound classes with specific biological activities. A variety of scaffold analyses have been carried out to derive statistics for scaffold distributions, generate structural organization schemes, or identify scaffolds that preferentially occur in given compound activity classes. Herein we further extend scaffold analysis by identifying scaffolds that display defined SAR profiles consisting of multiple properties. A structural relationship-based scaffold network has been designed as the basic data structure underlying our analysis. From network representations of scaffolds extracted from compounds active against 32 different target families, scaffolds with different SAR profiles have been extracted on the basis of decision trees that capture structural and functional characteristics of scaffolds in different ways. More than 600 scaffolds and 100 scaffold clusters were assigned to 10 SAR profiles. These scaffold sets represent different activity and target selectivity profiles and are provided for further SAR investigations including, for example, the exploration of alternative analog series for a given target of target family or the design of novel compounds on the basis of scaffold(s) with desired SAR profiles. PMID- 22091692 TI - A new multimodal geriatric discharge-planning intervention to prevent emergency visits and rehospitalizations of older adults: the optimization of medication in AGEd multicenter randomized controlled trial. AB - OBJECTIVES: To determine whether a new multimodal comprehensive discharge planning intervention would reduce emergency rehospitalizations or emergency department (ED) visits for very old inpatients. DESIGN: Six-month prospective, randomized (Zelen design), parallel-group, open-label trial. SETTING: Six acute geriatric units (AGUs) in Paris and its surroundings. PARTICIPANTS: Six hundred sixty-five consecutive inpatients aged 70 and older (intervention group (IG) n = 317; control group (CG) n = 348). INTERVENTION: Intervention-dedicated geriatricians different from those in the study centers implemented the intervention, which targeted three risk factors for preventable readmissions and consisted of three components: comprehensive chronic medication review, education on self-management of disease, and detailed transition-of-care communication with outpatient health professionals. MEASUREMENTS: Emergency hospitalization or ED visit 3 and 6 months after discharge, as assessed by telephone calls to the participant, the caregiver, and the general practitioner and confirmed with the hospital administrative database. RESULTS: Twenty-three percent of IG participants were readmitted to hospital or had an ED visit 3 months after discharge, compared with 30.5% of CG participants (P = .03); at 6 months, the proportions were 35.3% and 40.8%, respectively (P = .15). Event-free survival was significantly higher in the IG at 3 months (hazard ratio (HR) = 0.72, 95% confidence interval (CI) = 0.53-0.97, P = .03) but not at 6 months (HR = 0.81, 95% CI = 0.64-1.04, P = .10). CONCLUSION: This intervention was effective in reducing rehospitalizations and ED visits for very elderly participants 3 but not 6 months after their discharge from the AGU. Future research should investigate the effect of this intervention of transitional care in a larger population and in usual acute and subacute geriatric care. PMID- 22091694 TI - A brief response. PMID- 22091695 TI - Perceptuo-acoustic assessment of prosodic impairment in dysarthria. AB - Dysprosody was studied in four groups of male subjects: subjects with amyotrophic lateral sclerosis (ALS) and mild intelligibility impairment, subjects with ALS and a more severe intelligibility loss, subjects with cerebellar disease, and neurologically normal controls. Dysprosody was assessed with perceptual ratings and acoustic measures pertaining to the regulation of duration, f(0), and intensity within tone units of conversational samples. Intelligibility reduction and prosodic disturbance were not necessarily equally impaired in all subjects, and it is concluded that these are complementary indices of severity of dysarthria. Compared to the neurologically normal control group, the clinical groups tended to decrease the overall duration of tone units, produce fewer words in a tone unit, and use smaller variations in f(0). Recommendations are offered for the assessement of. PMID- 22091696 TI - Speaking rate, conversational speech acts, interruption, and linguistic complexity of 20 pre-school stuttering and non-stuttering children and their mothers. AB - This is the second in a series of reports concerning stuttering pre-school children enrolled in a longitudinal study; the first was Ryan (1992). Conversational samples of 20 stuttering and 20 non-stuttering pre-school children and their mothers were analysed for speaking rate, conversational speech acts, interruption, and linguistic complexity. Between-group analyses revealed few differences between either the two children or two mother groups. Within-group analyses indicated differences that involved conversational speech acts and linguistic complexity. Most stuttering occurred on statements (M = 32.3% stuttered) and questions (M = 20.9% stuttered). Stuttered and disfluent sentences had higher Developmental Sentence Scoring (DSS) (Lee, 1974) scores (M = 10.9, 12.9, respectively) than fluent sentences (M = 7.6). Multiple correlation analyses indicated that speaking rate of mothers (0.561) and normal disfluency of children (0.396) were major predictor variables. PMID- 22091697 TI - A phonological system at 2 years after cochlear implantation. AB - This report is a description of a developing phonological system as manifested in the productions of a prelingually deafened child approximately 2 years after fitting with a Nucleus 22-Channel Multi-Electrode Cochlear Implant. A probe list consisting of 23 proper nouns familiar to the child was used to elicit samples of her speech; stimulus materials consisted of photographs of those persons (friends and family members) whose names were included in the probe list. Analysis of the child's productions addressed the composition of the phonetic inventory of consonants and vowels and the presence of syllable structure and other phonotactic constraints. Results indicated a rich inventory of speech sound segments (among both consonants and vowels) and a lack of stringent constraints on syllable structure and consonants permitted in specified word positions. A further comparative analysis of correspondences with the ambient language showed a number of patterns that are also common in the speech of children with normal hearing. PMID- 22091699 TI - Moving toward the circular economy: the role of stocks in the Chinese steel cycle. AB - As the world's largest CO(2) emitter and steel producer, China has set the ambitious goal of establishing a circular economy which aims at reconciling economic development with environmental protection and sustainable resource use. This work applies dynamic material flow analysis to forecast production, recycling, and iron ore consumption in the Chinese steel cycle until 2100 by using steel services in terms of in-use stock per capita as driver of future development. The whole cycle is modeled to determine possible responses of the steel industry in light of the circular economy concept. If per-capita stock saturates at 8-12 tons as evidence from industrialized countries suggests, consumption may peak between 2015 and 2020, whereupon it is likely to drop by up to 40% until 2050. A slower growing in-use stock could mitigate this peak and hence reduce overcapacity in primary production. Old scrap supply will increase substantially and it could replace up to 80% of iron ore as resource for steel making by 2050. This would require advanced recycling technologies as manufacturers of machinery and transportation equipment would have to shift to secondary steel as well as new capacities in secondary production which could, however, make redundant already existing integrated steel plants. PMID- 22091700 TI - In situ synthesis of polymer-modified mesoporous carbon CMK-3 composites for CO2 sequestration. AB - Here we report carbon-based composites polyethylenimine-mesocarbon (PEI-CMK-3) and polyvinylamine-mesocarbon (PVA-CMK-3) that can be used to capture and rapidly release CO(2). CO(2) uptake by the synthesized composites was determined using a gravimetric method at 30 degrees C and 1 atm; the 39% PEI-CMK-3 composite had ~12 wt % CO(2) uptake capacity and the 37% PVA-CMK-3 composite had ~13 wt % CO(2) uptake capacity. A desorption temperature of 75 degrees C was sufficient for regeneration. The CO(2) uptake was the same when using 10% CO(2) in a 90% CH(4), C(2)H(6), and C(3)H(8) mixture, underscoring this composite's efficacy for CO(2) sequestration from natural gas. PMID- 22091701 TI - Mechanism of S-oxygenation by a cysteine dioxygenase model complex. AB - In this work, we present the first computational study on a biomimetic cysteine dioxygenase model complex, [Fe(II)(LN(3)S)](+), in which LN(3)S is a tetradentate ligand with a bis(imino)pyridyl scaffold and a pendant arylthiolate group. The reaction mechanism of sulfur dioxygenation with O(2) was examined by density functional theory (DFT) methods and compared with results obtained for cysteine dioxygenase. The reaction proceeds via multistate reactivity patterns on competing singlet, triplet, and quintet spin state surfaces. The reaction mechanism is analogous to that found for cysteine dioxygenase enzymes (Kumar, D.; Thiel, W.; de Visser, S. P. J. Am. Chem. Soc. 2011, 133, 3869-3882); hence, the computations indicate that this complex can closely mimic the enzymatic process. The catalytic mechanism starts from an iron(III)-superoxo complex and the attack of the terminal oxygen atom of the superoxo group on the sulfur atom of the ligand. Subsequently, the dioxygen bond breaks to form an iron(IV)-oxo complex with a bound sulfenato group. After reorganization, the second oxygen atom is transferred to the substrate to give a sulfinic acid product. An alternative mechanism involving the direct attack of dioxygen on the sulfur, without involving any iron-oxygen intermediates, was also examined. Importantly, a significant energetic preference for dioxygen coordinating to the iron center prior to attack at sulfur was discovered and serves to elucidate the function of the metal ion in the reaction process. The computational results are in good agreement with experimental observations, and the differences and similarities of the biomimetic complex and the enzymatic cysteine dioxygenase center are highlighted. PMID- 22091702 TI - Estrogen-anchored pH-sensitive liposomes as nanomodule designed for site-specific delivery of doxorubicin in breast cancer therapy. AB - The present investigation reports the development of nanoengineered estrogen receptor (ER) targeted pH-sensitive liposome for the site-specific intracellular delivery of doxorubicin (DOX) for breast cancer therapy. Estrone, a bioligand, was anchored on the surface of pH-sensitive liposome for drug targeting to ERs. The estrone-anchored pH-sensitive liposomes (ES-pH-sensitive-SL) showed fusogenic potential at acidic pH (5.5). In vitro cytotoxicity studies carried out on ER positive MCF-7 breast carcinoma cells revealed that ES-pH-sensitive-SL formulation was more cytotoxic than non-pH-sensitive targeted liposomes (ES-SL). The flow cytometry analysis confirmed significant enhanced uptake (p < 0.05) of ES-pH-sensitive-SL by MCF-7 cells. Intracellular delivery and nuclear localization of the DOX was confirmed by fluorescence microscopy. The mechanism for higher cytotoxicity shown by estrone-anchored pH-sensitive liposomal-DOX was elucidated using reactive oxygen species (ROS) determination. The in vivo biodistribution studies and antitumor activities of formulations were evaluated on tumor bearing female Balb/c mice followed by intravenous administration. The ES-pH-sensitive-SL efficiently suppressed the breast tumor growth in comparison to both ES-SL and free DOX. Serum enzyme activities such as LDH and CPK levels were assayed for the evaluation of DOX induced cardiotoxicity. The ES-pH sensitive-SL accelerated the intracellular trafficking of encapsulated DOX, thus increasing the therapeutic efficacy. The findings support that estrone-anchored pH-sensitive liposomes could be one of the promising nanocarriers for the targeted intracellular delivery of anticancer agents to breast cancer with reduced systemic side effects. PMID- 22091703 TI - A 1,3-dihydro-1,3-azaborine debuts. AB - We present the first synthesis and characterization of a 1,3-dihydro-1,3 azaborine, a long-sought BN isostere of benzene. 1,3-Dihydro-1,3-azaborine is a stable structural motif with considerable aromatic character as evidenced by structural analysis and its reaction chemistry. Single crystal X-ray analysis indicates bonding consistent with significant electron delocalization. 1,3 Dihydro-1,3-azaborines also undergo nucleophilic substitutions at boron and electrophilic aromatic substitution reactions. In view of the versatility and impact of aromatic compounds in the biomedical field and in materials science, the present study further expands the available chemical space of arenes via BN/CC isosterism. PMID- 22091704 TI - Necessary and sufficient conditions for equality of sibling and parent-offspring risk of a disease endophenotype in case families. AB - A large number of linkage and association studies of complex diseases focus on analysis of a more common or more easily measured disease endophenotype. The motivation for this approach is that there is a pleiotropic locus common to both the disease and the endophenotype and that this locus is a major genetic determinant of the endophenotype. In this paper, we determine the conditions under which the risk of the endophenotype in siblings of affected probands with disease equals the risk of the endophenotype in the offspring (parents) of affected parents (offspring) with disease. In doing so we prove that this equality holds if and only if the penetrance of either the endophenotype or the disease (but not necessarily both) is additive. PMID- 22091705 TI - On the relationship between temperament, metacognition, and anxiety: independent and mediated effects. AB - The present study examined the relations between temperamental traits distinguished in regulative theory of temperament, state anxiety, and metacognition as postulated in self-regulatory executive function (S-REF) theory of emotional disorder. Data analysis (n=315) consisted of independent and mediated effect analyses. Of the six traits, briskness, emotional reactivity and perseveration correlated significantly with both state anxiety and metacognitions (emotional reactivity and perseveration correlated positively, and briskness - negatively). These traits were predictors of state anxiety. Metacognition predicted state anxiety and relationships were independent of temperament. A mediating effect of metacognition was confirmed for the general index as well as negative and positive belief subscales. The findings support the metacognitive model of psychopathology and suggest that temperament is associated with metacognitions implicated in psychopathology and may have both direct and metacognitively mediated effects on anxiety. PMID- 22091709 TI - Psychological sweating from glabrous and nonglabrous skin surfaces under thermoneutral conditions. AB - Recent experiments revealed psychological sweating to be a ubiquitous phenomenon in passively heated individuals. Since heating potentiates sweating, and since most research into psychological sweating was not conducted in this thermal state, these observations required thermoneutral verification. Thermoneutral subjects performed mental arithmetic (at 26(o) C) with psychological sweating evaluated from nine sites (ventilated capsules, skin conductance). Discharged sweating was evident from three glabrous sites (P < .05). However, significant sweating was evident from two nonglabrous surfaces (P < .05), and skin conductance increased at the volar and dorsal finger surfaces (P < .05). Each of these changes occurred while core and skin temperatures remained stable (P > .05). These thermoneutral observations further refute the proposition that psychological sweating in humans is restricted to the glabrous skin surfaces. PMID- 22091708 TI - Newly diagnosed epileptic seizures: focus on an elderly population on the French island of Reunion in the Southern Indian Ocean. AB - PURPOSE: To describe seizure types and risk factors among elderly people with newly diagnosed epileptic seizures living on La Reunion, a French Island in the Southern Indian Ocean. METHODS: We describe an elderly population with newly diagnosed epileptic seizures using data from the EPIREUN study conducted between July 1, 2004 and June 30, 2005. The methodology is described in detail in the EPIREUN study report (Mignard et al., 2009). KEY FINDINGS: There were 153 single unprovoked seizures (84.1%); their incidence was 278.1 [95% confidence interval (CI) 237.4-325.9] per 100,000. The incidence of newly diagnosed epilepsy was 125.4 (95% CI, 99.1-158.8) per 100,000. Twenty-eight acute symptomatic seizures occurred (15.4%); the incidence was 50.9 (95% CI 35.1-73.7) per 100,000. The annual incidence of newly diagnosed epileptic seizure in the elderly was 330.8 (95% CI 286.1-382.6) per 100,000: 403.0 (95% CI 328.5-494.3) per 100,000 in men and 279.6 (95% CI, 227.4-343.8) per 100,000 in women. Sex had a significant (p = 0.014) effect on incidence: elderly men had a risk ratio of 1.44 compared to women of developing a newly diagnosed epileptic seizure. The etiology of single unprovoked seizure was as follows: stroke, 77 cases (50.3%); cryptogenic, 36 (23.5%); alcoholism, 10 (6.6%); a combination of several causes such as polypathology, 9 (5.9%); degenerative disease, 6 (4.0%); HIV infection, 2 (2.0%), and undetermined causes (2.7%). Most patients (170; 93.4%) were hospitalized, and 110 (60.8%) were treated. Among patients treated, 49 (44.5%) were given sodium valproate, 25 (22.7%) benzodiazepines, 12 (10.9%) phenytoin, 9 (8.2%) lamotrigine, 8 (7.3%) Trileptal, and 7 (6.4%) gabapentin. SIGNIFICANCE: Our findings show that the incidences of newly diagnosed epileptic seizures and newly diagnosed epilepsy were high in the elderly population of La Reunion. These incidences were significantly higher in men than in women. These results may be attributable to the high incidence of cerebrovascular diseases and comorbidities in this population. PMID- 22091711 TI - From individual cell motility to collective behaviors: insights from a prokaryote, Myxococcus xanthus. AB - In bird flocks, fish schools, and many other living organisms, regrouping among individuals of the same kin is frequently an advantageous strategy to survive, forage, and face predators. However, these behaviors are costly because the community must develop regulatory mechanisms to coordinate and adapt its response to rapid environmental changes. In principle, these regulatory mechanisms, involving communication between individuals, may also apply to cellular systems which must respond collectively during multicellular development. Dissecting the mechanisms at work requires amenable experimental systems, for example, developing bacteria. Myxococcus xanthus, a Gram-negative delatproteobacterium, is able to coordinate its motility in space and time to swarm, predate, and grow millimeter-size spore-filled fruiting bodies. A thorough understanding of the regulatory mechanisms first requires studying how individual cells move across solid surfaces and control their direction of movement, which was recently boosted by new cell biology techniques. In this review, we describe current molecular knowledge of the motility mechanism and its regulation as a lead-in to discuss how multicellular cooperation may have emerged from several layers of regulation: chemotaxis, cell-cell signaling, and the extracellular matrix. We suggest that Myxococcus is a powerful system to investigate collective principles that may also be relevant to other cellular systems. PMID- 22091712 TI - Deaths from violence in Britain: A tentative secular survey. AB - Abstract In recent years about 7,500 persons have been killed annually in road accidents in Britain. This 'slaughter on the roads' represents a mortality rate of around 150 per million persons living per annum (henceforth, pMa). 1 The vast majority of deaths occurred in accidents involving motor vehicles, 2 of which there were approximately 14 million in Britain in 1968. 3 Four decades ago the number ofmotor vehicles was less than one-quarter ofthat to-day (in 1934, 2.4 million): nevertheless, in the 1930's the mortality rate from motor vehicle accidents was almost identical with that of to-day. Clearly, though road traffic has increased and more persons expose themselves to the risks, with much longer exposure for some, man's mastery over the motor vehicle, social as well as technical, has correspondingly increased in recent decades. Individual vehicles are much less likely to be involved in fatal accidents, and for those who travel in vehicles (though conceivably not for pedestrians) the roads are no more dangerous, despite the increased traffic. PMID- 22091710 TI - A typical preparation of Francisella tularensis O-antigen yields a mixture of three types of saccharides. AB - Tularemia is a severe infectious disease in humans caused by the Gram-negative bacterium Francisella tularensis (Ft). Because of its low infectious dose, high mortality rate, and the threat of its large-scale dissemination in weaponized form, development of vaccines and immunotherapeutics against Ft is essential. Ft lipopolysaccharide (LPS), which contains the linear graded-length saccharide component O-antigen (OAg) attached to a core oligosaccharide, has been reported as a protective antigen. Purification of LPS saccharides of defined length and composition is necessary to reveal the epitopes targeted by protective antibodies. In this study, we purified saccharides from LPS preparations from both the Ft subspecies holarctica live vaccine strain (LVS) and the virulent Ft subspecies tularensis SchuS4 strain using liquid chromatography. We then characterized the fractions using high-resolution mass spectrometry and tandem mass spectrometry. Three types of saccharides were observed in both the LVS and SchuS4 preparations: two consisting of OAg tetrasaccharide repeats attached to one of two core oligosaccharide variants and one consisting of tetrasaccharide repeats only (coreless). The coreless OAg oligosaccharides were shown to contain Qui4NFm (4,6-dideoxy-4-formamido-D-glucose) at the nonreducing end and QuiNAc (2 acetamido-2,6-dideoxy-O-D-glucose) at the reducing end. Purified homogeneous preparations of saccharides of each type will allow mapping of protective epitopes in Ft LPS. PMID- 22091713 TI - A Marxian-Malthusian view of poverty and development. AB - Abstract The names of Marx and Malthus are often linked in disjunction but never in conjunction. Nevertheless, the thesis argued in this paper is that the two historically dominant theories of poverty, the Marxian and the Malthusian, are not inconsistent, but complementary; that a union of the two yields a basic fourfold typology of social classes by differential ownership of property and differential fertility; that this typology can also be viewed as a way of disaggregating the meaningless average of 'GNP per head' in a way which gives social content (i.e. a distributional dimension) to the concept; that the typology provides more satisfactory definitions of 'development' and 'overpopulation'; and that these four categories are improved, or usefully supplemented, by replacing the flowof income by the stock of wealth in each case. Also the universality of the typology is discussed along with some preliminary empirical considerations. PMID- 22091714 TI - The influence of fluctuations in economic conditions on fertility and marriage rates, Australia, 1920-21 to 1937-38 and 1946-47 to 1966-67. AB - Abstract It has been widely observed that both cross-sectionally and secularly there has been a negative relationship between income or level of living and the family size of married females. 1 At the same time the relationship between economic indicators and current fertility with a lag of one or more years over the business cycle has been found to be strongly positive. In fact the persistence of the latter relationship over a wide area and varying periods led Dr. Thomas to remark that it has been one of the most firmly based empirical findings in any of the social sciences. PMID- 22091715 TI - Factors affecting fertility of natives and migrants in urban Brazil. AB - Abstract Modernization is expected to change the patterns of population growth of developing countries. The primary reason explaining the fast rate of population growth of these nations has been established as that of the reductions of mortality! which marks the first stage of demographic transition. The second stage in this process is the reduction in fertility which counterbalances lowered mortality and therefore reduces the rate of population growth. This latter phase has been achieved in modern industrial societies. PMID- 22091716 TI - Migration as a means of population control. AB - Abstract The more crowded West Indian islands lose citizens each year through emigration, and they are small enough for an appreciable relief of population pressure to be thereby afforded. Each year some of the inhabitants of Java move to Sumatra and elsewhere under official sponsorship, part of the rationale for the policy being the relief of population pressure; a recent definitive study covers the movement in detail. PMID- 22091717 TI - Ages at menarche and menopause: Some mediaeval authorities. AB - Abstract It is well known that the duration of the fecund period in the female has not been constant, in the last couple of centuries at least. Tanner(1) has assembled the best menarche statistics currently available for Western peoples in the nineteenth and twentieth centuries, and has concluded that the average age at menarche has fallen fairly consistently, at a rate of four months per decade, since c. 1830. This puts menarche somewhere between 15+ and 17+ in the second quarter of the nineteenth century, against equivalent figures of 12+ and 14 in the mid-twentieth. For earlier periods Tanner's methods cannot be applied because of the lack of clinical data of the order he requires; but Backman, in a more general survey, concluded that in classical antiquity the time of menarche was fairly constant at around the age of fourteen and probably remained at about that age until the beginning of the modern era, But c. 1500, or earlier, a retardation of menarche began throughout Europe ... By the end of the eighteenth century this process of retardation had produced the very high figure of 17.5-18 years, at least in northern Europe. In the early nineteenth century, perhaps c. 1830, there began a progressive decline in the age of menarche, which now seems to be levelling out at around the age of 14.0-14.5. PMID- 22091718 TI - Estimates of population size and growth from the 1952-54 and 1961 censuses of the Kingdom of Nepal. AB - Abstract The Census of Nepal conducted in 1961 conforms to the generally accepted requirements for a national census. Some doubt could be raised about the previous census as part of the country was enumerated in 1952 and part in 1954. More serious doubts still could be entertained about earlier censuses, including their very existence, though there are persistent rumours that they were carried out every ten years or so since about the middle of the previous century. We have only been able to lay our hands on some data in respect of four earlier censuses: those of 1911, 1920, 1930 and 1941. Little more is available than population totals for some of the component areas from these four censuses, and even then the boundaries and coverage of the component parts are uncertain. PMID- 22091719 TI - Child-spacing differentials for white and non-white couples according to educational level of attainment for the 1/1000 sample of the United States population in 1960. AB - Abstract Despite previous research on the relationship between husband's or wife's level of educational attainment and childbearing and child spacing, relatively few data exist on couples' combined educational attainment which compares whites and non-whites. Further, to date a systematic exploration of available information contained on the 1/1,000 sample of the United States population in 1960 has not been undertaken. This paper utilizes these data and investigates the time intervals between marriage and first birth and between subsequent events to determine what relationships exist between parity and child spacing for white and non-white couples by level of educational attainment. PMID- 22091720 TI - A cost-benefit model of rural to urban migration in Taiwan. AB - Abstract Migration is a form of human behaviour which has lent itself to careful measurement for a relatively long period of time. In 1885 Ravenstein set forth certain empirical laws concerning the relationship of migration to age and distance which have held up to the present. Since then an abundance of migration data has enabled social scientists to develop more precise models relating the volume or rate of migration to characteristics of the migrants or of the areas of origin and destination. Prominent among these models are the gravity model, the intervening opportunities model, a gravity type model including wage rates and unemployment rates developed by Lowry, and the Cornell mobility model. PMID- 22091721 TI - Plague mortality rates by age and sex in the parish of St. Botolph's without Bishopsgate, London, 1603. AB - Abstract The Bills of Mortality for London were instituted at least as early as 1528 but only a few figures survive before the extant annual series that begins in 1603. Ages at death, even in broad groups of ages, are not generally available until 1728, which is more than 50 years too late to give us any inkling of the ages, if any, at which people were specially susceptible to plague. There are reports, it is true, that suggest that children suffered from plague more severely than adults, at least on certain occasions (as in 1361 or 1418 for example), but nothing more precise. The legend of the Pied Piper of Hamelin may be a folk-memory of a plague (possibly in 1284) that killed mainly the children of the town, for the connection between infestation of rats and the loss of children suggests some kind of plague outbreak. Pollitzer concludes that no particular age group is specially liable to plague, and attributes all differences observed to different risks of exposure. The determinants of the severity of an outbreak would therefore be the environmental details and social customs. PMID- 22091722 TI - Those alleged pitfalls. AB - Abstract The following comments apply only to those remarks of Professor Leibenstein that can be treated very briefly. PMID- 22091723 TI - A final remark on pitfalls. AB - Abstract I agree that criticism is relatively easy. Further, I should like to repeat that the contributions made by Enke and others in calculating cost-benefit estimates have been stimulating. However, at a time when the so-called 'population explosion' has become a hot topic in the mass media and elsewhere there is some danger of overselling the results. To me it seems that relatively little criticism has been ventured in the past. Of course, I cannot prove this, but I suspect that most readers have a bias (as I do) in favour of birth control, and we seldom feel compelled to ferret out definciencies in procedures that lead to results which are in accord with out tastes. PMID- 22091726 TI - Targeting post-translational modifications on tau as a therapeutic strategy for Alzheimer's disease. AB - Alzheimer's disease (AD) is a neurodegenerative disorder that causes early memory impairment, followed by profound progressive cognitive decline, and eventually death. Neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of AD. NFTs are deposits of insoluble aggregates of the microtubule-binding protein tau, left behind following neuronal loss. Intracellular aggregates of tau, either in soluble or insoluble forms, are thought to disrupt cellular machinery and synaptic function and ultimately lead to neuronal death. As the ultimate pathological endpoint in AD is neuronal loss, there is significant interest in understanding the causes of tau aggregation and deposition in the brain as a potential therapeutic avenue for AD. Post-translational modifications on tau are thought to be an important regulatory mechanism that may contribute to the propensity of tau to aggregate and form NFTs. In addition to phosphorylation, numerous other post-translational modifications have been observed on tau protein. The mechanisms that cause aggregation of tau are unknown, but it is likely that post-translational modifications other than phosphorylation also regulate this process. This review will discuss several post-translational modifications of tau and their roles in modulation of tau function and aggregation in AD. PMID- 22091727 TI - Characterization of an mGluR2/3 negative allosteric modulator in rodent models of depression. AB - There is growing evidence suggesting that antagonists of group II metabotropic glutamate receptors (mGluR2/3) exhibit antidepressant-like properties in several preclinical models of depression. However, all those studies have been performed using competitive group II non-selective orthosteric antagonists. In this study we extensively characterized a group II selective negative allosteric modulator (4-[3-(2,6-Dimethylpyridin-4-yl)phenyl]-7-methyl-8-trifluoromethyl-1,3 dihydrobenzo[b][1,4]diazepin-2-one, namely RO4491533, Woltering et al., 2010) in several in vitro biochemical assays and in vivo models of depression. In vitro, RO4491533 completely blocked the glutamate-induced Ca(2+) mobilization and the glutamate-induced accumulation in [(35)S]GTP(gammaS) binding in cells expressing recombinant human or rat mGluR2 and in native tissues. Results from Schild plot experiments and reversibility test at the target on both cellular and membrane based assays confirmed the negative allosteric modulator properties of the compound. RO4491533 was equipotent on mGluR2 and mGluR3 receptors but not active on any other mGluRs. RO4491533 has acceptable PK properties in mice and rats, is bioavailable following oral gavage (F = 30%) and brain-penetrant (CSF conc/total plasma conc ratio = 0.8%). RO4491533 appeared to engage the central mGluR2 and mGluR3 receptors since the compound reversed the hypolocomotor effect of an mGluR2/3 orthosteric agonist LY379268 in a target-specific manner, as did the group II orthosteric mGluR2/3 antagonist LY341495. RO4491533 and LY341495 dose dependently reduced immobility time of C57Bl6/J mice in the forced swim test. Also, RO4491533 and LY341495 were active in the tail suspension test in a line of Helpless (H) mice, a putative genetic model of depression. These data suggest that mGluR2/3 receptors are viable targets for development of novel pharmacotherapies for depression. PMID- 22091728 TI - Pharmacological validation of candidate causal sleep genes identified in an N2 cross. AB - Despite the substantial impact of sleep disturbances on human health and the many years of study dedicated to understanding sleep pathologies, the underlying genetic mechanisms that govern sleep and wake largely remain unknown. Recently, the authors completed large-scale genetic and gene expression analyses in a segregating inbred mouse cross and identified candidate causal genes that regulate the mammalian sleep-wake cycle, across multiple traits including total sleep time, amounts of rapid eye movement (REM), non-REM, sleep bout duration, and sleep fragmentation. Here the authors describe a novel approach toward validating candidate causal genes, while also identifying potential targets for sleep-related indications. Select small-molecule antagonists and agonists were used to interrogate candidate causal gene function in rodent sleep polysomnography assays to determine impact on overall sleep architecture and to evaluate alignment with associated sleep-wake traits. Significant effects on sleep architecture were observed in validation studies using compounds targeting the muscarinic acetylcholine receptor M3 subunit (Chrm3) (wake promotion), nicotinic acetylcholine receptor alpha4 subunit (Chrna4) (wake promotion), dopamine receptor D5 subunit (Drd5) (sleep induction), serotonin 1D receptor (Htr1d) (altered REM fragmentation), glucagon-like peptide-1 receptor (Glp1r) (light sleep promotion and reduction of deep sleep), and calcium channel, voltage dependent, T type, alpha 1I subunit (Cacna1i) (increased bout duration of slow wave sleep). Taken together, these results show the complexity of genetic components that regulate sleep-wake traits and highlight the importance of evaluating this complex behavior at a systems level. Pharmacological validation of genetically identified putative targets provides a rapid alternative to generating knock out or transgenic animal models, and may ultimately lead towards new therapeutic opportunities. PMID- 22091729 TI - Phenotypic variability in a large Czech family with a dynamin 2-associated Charcot-Marie-Tooth neuropathy. AB - Mutations in the Dynamin 2 gene (DNM2) cause autosomal dominant centronuclear myopathy or autosomal dominant (AD) Charcot-Marie-Tooth (CMT) disease. Here the authors report one large Czech family with 15 members affected with an AD CMT phenotype of extraordinary variability. Genetic linkage analysis using SNP arrays revealed a locus of about 9.6 Mb on chromosome 19p13.1-13.2. In this critical interval, 373 genes were located. The only gene herein known to be associated with an intermediate type of CMT was Dynamin 2 (DNM2). Subsequent sequence analysis of the DNM2 gene in the index patient revealed a novel missense mutation p.Met580Thr. This missense mutation segregated with the neuropathy, indicating the causal character of this mutation. The phenotype of CMT in this family shows mild to moderate impairment with relatively preserved upper limbs and a very broad range of the onset of clinical symptoms from an early onset around the age of 12 to the late onset during the fifth decade. Electrophysiology showed an intermediate type of peripheral neuropathy. The motor median nerve conduction velocity varied from 36 m/s to normal values with signs of asymmetrical affection of peripheral nerves. No additional symptoms such as cranial nerve involvement, cataract, and signs of neutropenia or myopathy syndrome were observed in any member of the family yet. The progression was slow with no loss of ambulation. The authors suggest that the characterization of clinical variability in a single family may help to direct the genetic analysis directly to the rarely observed DNM2 mutations. PMID- 22091730 TI - An interacting multiple model filter-based autofocus strategy for confocal time lapse microscopy. AB - Gene expression and other cellular processes are stochastic, thus their study requires observing multiple events in multiple cells. Therefore, confocal microscopy cell imaging has recently gained much interest. In time-lapse imaging, adjustments are needed at short intervals to compensate for focus drift. There are several automated methods for this purpose. In general, before acquiring higher resolution images, software-based autofocus algorithms require a set of low-resolution images along the z-axis to determine the plane for which a predefined focusing function is maximized. These algorithms require 10-100 z slices each time, and there is no fixed number or upper limit of required z slices that ensures optimal focusing. The higher is this number, the stronger is photo bleaching, hampering the feasibility of long-time series measurements. We propose a new focusing strategy in time-lapse imaging. The algorithm relies on the nature and predictability of the focus drift. We first show that the focus drift curve is predictable within a small error bound in standard experimental setups. We, then, exploit the interacting multiple model filter algorithm to predict the drift at time, t, based on the measurement at time t-1. This allows a drastic reduction of the number of required z-slices for focus drift correction, largely overcoming the problem of photo bleaching. In addition, we propose a new set of functions for focusing in time-lapse imaging, derived from preexisting ones. We demonstrate the method's efficiency in time-lapse imaging of Escherichia coli cells expressing MS2d-GFP tagged RNA molecules. PMID- 22091731 TI - Bilobetin ameliorates insulin resistance by PKA-mediated phosphorylation of PPARalpha in rats fed a high-fat diet. AB - BACKGROUND AND PURPOSE: The amelioration of insulin resistance by bilobetin is closely related to its hypolipidaemic effect. The aim of the present study was to determine the insulin-sensitizing mechanism of bilobetin by elucidating its effect on lipid metabolism. EXPERIMENTAL APPROACH: Rats fed a high-fat diet were treated with bilobetin for either 4 or 14 days before applying a hyperinsulinaemic-euglycaemic clamp. Triglyceride and fatty acids labelled with radioactive isotopes were used to track the transportation and the fate of lipids in tissues. The activity of lipid metabolism-related enzymes and beta-oxidation rate were measured. Western blot was used to investigate the phosphorylation, translocation and expression of PPARalpha in several tissues and cultured cells. The location of amino acid residues subjected to phosphorylation in PPARalpha was also studied. KEY RESULTS: Bilobetin ameliorated insulin resistance, increased the hepatic uptake and oxidation of lipids, reduced very-low-density lipoprotein triglyceride secretion and blood triglyceride levels, enhanced the expression and activity of enzymes involved in beta-oxidation and attenuated the accumulation of triglycerides and their metabolites in tissues. Bilobetin also increased the phosphorylation, nuclear translocation and activity of PPARalpha accompanied by elevated cAMP level and PKA activity. Threonine-129-alanine and/or serine-163 alanine mutations on the PPARalpha genes and PKA inhibitors prevented the effects of bilobetin on PPARalpha. However, cells overexpressing PKA appeared to stimulate the phosphorylation, nuclear translocation and activity of PPARalpha. CONCLUSIONS AND IMPLICATIONS: Bilobetin treatment ameliorates hyperlipidaemia, lipotoxicity and insulin resistance in rats by stimulating PPARalpha-mediated lipid catabolism. PKA activation is crucial for this process. PMID- 22091732 TI - Costs of addressing heroin addiction in Malaysia and 32 comparable countries worldwide. AB - OBJECTIVE: Develop and apply new costing methodologies to estimate costs of opioid dependence treatment in countries worldwide. DATA SOURCES/STUDY SETTING: Micro-costing methodology developed and data collected during randomized controlled trial (RCT) involving 126 patients (July 2003-May 2005) in Malaysia. Gross-costing methodology developed to estimate costs of treatment replication in 32 countries with data collected from publicly available sources. STUDY DESIGN: Fixed, variable, and societal cost components of Malaysian RCT micro-costed and analytical framework created and employed for gross-costing in 32 countries selected by three criteria relative to Malaysia: major heroin problem, geographic proximity, and comparable gross domestic product (GDP) per capita. PRINCIPAL FINDINGS: Medication, and urine and blood testing accounted for the greatest percentage of total costs for both naltrexone (29-53 percent) and buprenorphine (33-72 percent) interventions. In 13 countries, buprenorphine treatment could be provided for under $2,000 per patient. For all countries except United Kingdom and Singapore, incremental costs per person were below $1,000 when comparing buprenorphine to naltrexone. An estimated 100 percent of opiate users in Cambodia and Lao People's Democratic Republic could be treated for $8 and $30 million, respectively. CONCLUSIONS: Buprenorphine treatment can be provided at low cost in countries across the world. This study's new costing methodologies provide tools for health systems worldwide to determine the feasibility and cost of similar interventions. PMID- 22091733 TI - Exposure to acute stress is associated with attenuated sweet taste. AB - This study examined the effects of stress on taste perception. Participants (N = 38; 21 women) completed two laboratory sessions: one stress (public speaking, math, and cold pressor) and one control rest session. The taste perception test was conducted at the end of each session and included rating the intensity and pleasantness of sweet, salty, sour, and savory solutions at suprathreshold concentrations. Cardiovascular, hormonal, and mood measures were collected throughout the sessions. Participants showed the expected changes in cardiovascular, hormonal, and mood measures in response to stress. Reported intensity of the sweet solution was significantly lower on the stress day than on the rest day. Cortisol level poststress predicted reduced intensity of salt and sour, suggesting that stress-related changes in adrenocortical activity were related to reduced taste intensity. Results indicate that acute stress may alter taste perception, and ongoing research investigates the extent to which these changes mediate effects of stress on appetite. PMID- 22091734 TI - Forces applied to the maxillary incisors by video laryngoscopes and the Macintosh laryngoscope. AB - BACKGROUND: Modern video laryngoscopes (VLSs) provide a superior view of the glottis, facilitating easier intubations. This study evaluates the forces applied to the maxillary incisors when using various VLSs and a Macintosh blade. METHODS: Fifty consecutive surgery patients were randomly assigned to receive laryngoscopy from a pair of four blades investigated in the study - the VLS GlideScope((r)) (Verathon Inc., Bothell, WA, USA), V-MacTM Storz((r)) (Karl Storz, Tuttlingen, Germany), and McGrathTM (Aircraft Medical, Edinburgh, United Kingdom); and the classic Macintosh blade also from Storz((r)) (Karl Storz). An endotracheal tube (ETT) was brought into position anterior to the vocal cords, with actual intubation carried out only with the second of the laryngoscopes. Sensors measured the forces directly applied to the patient's maxillary incisors while inserting the ETT. Other common metrics of intubation difficulty (e.g. Mallampati grade, Cormack-Lehane grade, and time) were also recorded. RESULTS: Only one patient was not intubated within the standard study parameters and was converted to the hospital protocols for difficult intubations. The forces applied to the maxillary incisors were significantly greater with the Macintosh blade compared with all VLSs. There were no differences between the VLSs with regard to the forces. Patient characteristics, including Mallampati grade, were not predictive of the forces applied. CONCLUSIONS: All VLSs considered were safer for the patient than was the Macintosh blade in terms of the forces applied to the maxillary teeth, time, number of insertion attempts, and view achieved of the glottic arch. There is a small, but significant, difference in the time and number of insertion attempts required during laryngoscopy with the different VLSs. There was no difference in the forces applied. The geometry of the respective blades may be an important component in the ease of laryngoscopy. PMID- 22091735 TI - Interaction terms in nonlinear models. AB - OBJECTIVES: To explain the use of interaction terms in nonlinear models. STUDY DESIGN: We discuss the motivation for including interaction terms in multivariate analyses. We then explain how the straightforward interpretation of interaction terms in linear models changes in nonlinear models, using graphs and equations. We extend the basic results from logit and probit to difference-in-differences models, models with higher powers of explanatory variables, other nonlinear models (including log transformation and ordered models), and panel data models. EMPIRICAL APPLICATION: We show how to calculate and interpret interaction effects using a publicly available Stata data set with a binary outcome. Stata 11 has added several features which make those calculations easier. LIMDEP code also is provided. CONCLUSIONS: It is important to understand why interaction terms are included in nonlinear models in order to be clear about their substantive interpretation. PMID- 22091736 TI - Modified ear canal ablation and lateral bulla osteotomy for management of otitis media in an alpaca. AB - OBJECTIVE: To report surgical treatment of severe otitis media in an alpaca by a modification of a subtotal ear canal ablation and lateral bulla osteotomy technique used in dogs. STUDY DESIGN: Case report. ANIMALS: An 11-week-old female alpaca cria. METHODS: The cria had a 2-week history of right otitis media, nonresponsive to medical treatment, as well as right facial nerve paralysis, and a melting corneal ulcer of the right eye. Otitis media was confirmed by computed tomography. Right subtotal ear canal ablation and lateral bulla osteotomy were performed using a modification of a technique reported in dogs. RESULTS: There were no surgical complications and the alpaca was discharged from the hospital 5 days later. At 10 months, moderate motor function had been restored to the pinna with the ear standing partially erect. The otitis had resolved, and the alpaca was reportedly well integrated into the herd. CONCLUSION: Subtotal ear canal ablation and lateral bulla osteotomy, a technique modified from that performed in dogs, were successful in providing complete clinical resolution of otitis media in an alpaca. PMID- 22091737 TI - Quantification of subfamily I.2.C catechol 2,3-dioxygenase mRNA transcripts in groundwater samples of an oxygen-limited BTEX-contaminated site. AB - Low dissolved oxygen concentration of subsurface environments is a limiting factor for microbial aromatic hydrocarbon degradation, and to date, there are only a limited number of available reports on functional genes and microbes that take part in the degradation of aromatic hydrocarbons under hypoxic conditions. Recent discoveries shed light on the prevalence of subfamily I.2.C catechol 2,3 dioxygenases in petroleum hydrocarbon contaminated hypoxic groundwaters, and their considerable environmental importance was suggested. Here, we report on a Hungarian aromatic hydrocarbon (methyl-substituted benzene derivatives, mostly xylenes) contaminated site where we investigated this presumption. Groundwater samples were taken from the center and the edge of the contaminant plume and beyond the plume. mRNA transcripts of subfamily I.2.C catechol 2,3-dioxygenases were detected in considerable amounts in the contaminated samples by qPCR analysis, while activity of subfamily I.2.A, which includes the largest group of extradiol dioxygenases described by culture-dependent studies and thought to be widely distributed in BTEX-contaminated environments, was not observed. Bacterial community structure analyses showed the predominance of genus Rhodoferax related species in the contaminated samples. PMID- 22091738 TI - Community aging in place, advancing better living for elders: a bio-behavioral environmental intervention to improve function and health-related quality of life in disabled older adults. AB - OBJECTIVES: To determine effect size and acceptability of a multicomponent behavior and home repair intervention for low-income disabled older adults. DESIGN: Prospective randomized controlled pilot trial. SETTING: Participants' homes. PARTICIPANTS: Forty low-income older adults with difficulties in one or more activities of daily living (ADLs) or two or more instrumental activities of daily living (IADLs). INTERVENTION: The Community Aging in Place, Advancing Better Living for Elders (CAPABLE), coordinated occupational therapy, nursing, and handyman visits, was compared with attention-control visits. The intervention consisted of up to six visits with an occupational therapist, up to four visits with a nurse, and an average of $1,300 in handyman repairs and modifications. Each intervention participant received all components of the intervention clinically individualized to risk profile and goals. Each attention-control participant received the same number of visits as the intervention participants, involving sedentary activities of their choice. MEASUREMENT: PRIMARY OUTCOME: difficulty in performing ADLs and IADLs. SECONDARY OUTCOMES: health-related quality of life and falls efficacy. RESULTS: Thirty-five of 40 adults (87%) completed the 6-month trial, and 93% and 100% of the control and intervention group, respectively, stated that the study benefited them. The intervention group improved on all outcomes. When comparing mean change in the intervention group with mean change in the control group from baseline to follow-up, the CAPABLE intervention had effect sizes of 0.63 for reducing difficulty in ADLs, 0.62 for reducing difficulty in IADLs, 0.89 for quality of life, and 0.55 for falls efficacy. CONCLUSION: The CAPABLE intervention was acceptable to participants and feasible to provide and showed promising results, suggesting that this multicomponent intervention to reduce disability should be evaluated in a larger trial. PMID- 22091739 TI - Adolescent substance use groups: antecedent and concurrent personality differences in a longitudinal study. AB - This study attempted to extend Shedler and Block's (1990) influential study, which found that adolescent drug experimenters had the healthiest personality functioning compared to abstainers and frequent users. Using a prospective design, we examined the relationship between antecedent and concurrent personality and age-18 substance use in a community sample of 1,298 twins (96% Caucasian, 49% male). Personality measures at ages 11 and 18 assessed positive emotionality (agentic and communal), negative emotionality, and constraint. Substance use groups-abstainers, experimenters, and problem users-were created at age 18. Age-18 substance use groups differed in age-11 and age-18 constraint such that problem users were lower than experimenters, who were lower than abstainers. Age-18 substance use groups did not differ in age-18 positive emotionality. However, abstainers were significantly lower than experimenters in communal positive emotionality, whereas female abstainers scored higher in agentic positive emotionality than female experimenters, who scored higher than female problem users. Experimenters were significantly lower in negative emotionality than problem users. Our findings are inconsistent with the notion that experimenters had the healthiest personality functioning and instead suggest different strengths and weaknesses for each group. Future studies should examine agentic and communal positive emotionality separately. PMID- 22091741 TI - Relationship between current psychological symptoms and future risk of asthma outcomes: a 12-month prospective cohort study. AB - BACKGROUND: Subjects with asthma are more susceptible to psychological symptoms, but it is uncertain whether psychological symptoms are linked to future risk of asthma outcomes. OBJECTIVE: To investigate the relationship between current psychological symptoms and future risk of asthma outcomes. METHODS: We conducted a prospective cohort study with a 12-month follow-up period of 297 patients with asthma. Psychological symptoms, lung function, asthma control test, and Asthma Quality of Life Questionnaire at baseline were assessed. Asthma outcomes including exacerbations, unplanned visits, emergency visits, hospital admissions, intensive care unit admissions, and length of hospital stays were monitored monthly. The time to the first asthma outcomes was analyzed. Furthermore, the association between psychological symptoms and future risk of asthma outcomes was calculated as adjusted relative risk (RR) using logistic regression models. RESULTS: The asthma patients were assigned to one of three groups: neither anxiety nor depression symptoms (NAD, n = 102), either anxiety or depression symptoms (A/D, n = 68), or anxiety and depression symptoms (AD, n = 120). Logistic regression models indicated that asthma patients in the AD group, but not the A/D group, had an increased adjusted RR for unplanned visits and emergency visits (RR = 2.33, 95% confidence interval (CI) = [1.50, 3.61]; and RR = 3.13, 95% CI = [1.90, 5.17], respectively). The time to the first asthma outcomes including exacerbations, unplanned visits, and emergency visits was shorter in patients with psychological symptoms than those without (all p < .001). CONCLUSION: Current psychological symptoms, especially anxiety combined with depression, independently predict the future risk of asthma outcomes. Ting Zhou and Lan Wang contributed equally to this study. PMID- 22091740 TI - Psychosocial outcomes are related to asthma control and quality of life in pregnant women with asthma. AB - BACKGROUND: Little is known about the psychosocial impact and perceived teratogenic (fetal harm due to medication) risks of asthma treatment (inhaled/oral corticosteroids and beta-agonist) during pregnancy. AIMS: To assess the perception of asthma control, quality of life (QoL), and perceived risks of therapy in pregnant women with asthma. METHODS: Pregnant women with asthma (n = 125) were recruited between 12 and 20 weeks gestation. QoL (generic: Short Form 12 Health Survey v1, and asthma specific: Asthma Quality of Life Questionnaire Marks (AQLQ-M)) and psychological variables were assessed using the Perceived Control of Asthma Questionnaire (PCAQ), the Brief Illness Perception Questionnaire, and the Six-Item Short-Form State Trait Anxiety Inventory (STAI 6). Women's perceptions of the teratogenic risks of asthma therapy were also assessed and analyzed for adherence to maintenance inhaled corticosteroids (ICSs), poor asthma control, and QoL. RESULTS: Women reported good QoL (median AQLQ-M total score/maximum score = 0.88/10), moderate ability to deal with asthma symptoms (mean PCAQ score = 42.6/55), positive beliefs about their asthma and low anxiety (median STAI score = 26.7/80). Perceived teratogenic risks for asthma drugs were excessive and class dependent. Women perceived there was a 42% teratogenic risk for oral corticosteroid, a 12% risk for ICSs, and a 5% risk with short-acting beta-agonist. Illness beliefs, emotional response to illness (p = .030), age >= 30 years (p = .046), and maintenance ICS use (p = .045) were significantly associated with uncontrolled asthma, while maintenance ICS use (p = .023), illness beliefs, consequences (p = .044), timeline (p = .016), and emotional response (p = .015) and anxiety (p <= .0001) were significantly associated with reduced QoL. CONCLUSIONS: In pregnancy, women with asthma experience good QoL but overestimate teratogenic risks of asthma medication. Maintenance ICS use, illness beliefs, and anxiety are associated with impaired QoL and asthma control. PMID- 22091742 TI - Concomitant asthma medication use by patients receiving omalizumab 2003-2008. AB - OBJECTIVE: To examine patterns of omalizumab use in the first 5 years of its availability. METHODS: Our study comprised a series of descriptive retrospective cohort analyses using healthcare claims data. The study population comprised patients of any age who had omalizumab claims in the 5 years after 1 July 2003, and we created five 1-year cohorts from this population. Each cohort included patients continuously enrolled for at least 12 months with >=2 omalizumab claims during the year. Cohorts contained between 302 and 1382 unique omalizumab users, and over 99% of patients with an omalizumab claim had at least one asthma diagnosis. RESULTS: In all years, the specialty most commonly seen in conjunction with the initial omalizumab prescription was allergy/immunology. In all years, omalizumab was used in conjunction with three or more additional classes of asthma medications at least 70% of the time and with five or more classes at least 33% of the time; the proportion of patients filling omalizumab prescriptions who had no other concomitant classes of asthma medications varied from 4% to 8%. The most common pattern of asthma medication treatment in all years was omalizumab with combination steroids/long-acting beta-agonist inhaler, a leukotriene receptor antagonist, a short-acting beta-agonist inhaler, and at least one course of oral corticosteroids. CONCLUSIONS: In this study of a large sample of commercial health insurance claims covering the first 5 years after approval of omalizumab, we found that omalizumab was infrequently used as a single agent or without concomitant inhaled corticosteroids, and most omalizumab prescriptions came from specialist physicians. PMID- 22091743 TI - Comparison of asthma control criteria: importance of spirometry. AB - AIMS: To compare the measurements of asthma control using Canadian Thoracic Society (CTS) Asthma Management Consensus Summary and Global Initiative for Asthma (GINA) guidelines composite indices with and without spirometry. METHODS: Asthma control parameters were extracted from electronic medical records (EMRs) of patients >=6 years old at two primary care sites. Asthma control ratings calculated according to CTS and GINA criteria were compared. RESULTS: Data were available from 113 visits by 93 patients, aged 6-85 years (38.7 +/- 24.8; mean +/ SD). The proportion of visits at which individuals' asthma was completely controlled was 22.1% for CTS symptoms only and 9.7% for CTS with spirometry (p < .01); and 17.7% versus 14.1% for GINA symptoms only versus symptoms with spirometry (p = .125). CONCLUSIONS: Asthma control ratings using GINA and CTS criteria are discordant in more than half of the patients deemed "in control" by at least one scale. Differences in the spirometry criterion threshold are primarily responsible for this discordance. Failure to include spirometry as part of the control index consistently overestimates asthma control and may underestimate future risk of exacerbations. PMID- 22091744 TI - Relationship between exercise-induced bronchospasm (EIB) and asthma control test (ACT) in asthmatic children. AB - OBJECTIVE: Evaluate the relationship between Asthma Control TestTM (ACT) and exercise-induced bronchospasm (EIB) in 81 asthmatic children. METHODS: EIB was assessed in every patient by Balke protocol and asthma control was evaluated by ACT. Patients were divided into three groups: Group A (30 patients) with complete asthma control (ACT score = 25), Group B (37 patients) with partial asthma control (ACT score = 21-24), and Group C (14 patients) with poor asthma control (ACT score < 20). RESULTS: About 36% (11/30) of patients in Group A (with complete asthma control) tested positive for EIB, whereas 21% (8/37) in Group B (with partial asthma control) and 28% (4/14) in Group C (with poor asthma control) exhibited EIB. The percentage of positive EIB was very similar between the three groups with no differences between controlled, partially controlled, and uncontrolled asthma. Statistical evaluation by chi(2)-test between complete (ACT score = 25) and not complete asthma control (ACT score < 24) confirmed a statistically significant difference (p < .01) between the obtained data. CONCLUSIONS: It must be stated that ACT alone is not sufficient to evaluate asthma control in children correctly because it fails to detect EIB in a significant percentage of subjects. PMID- 22091746 TI - Putting evidence for diabetes care into practice. AB - The amount of research and technology related to diabetes mellitus has grown dramatically over the past few decades. This knowledge has led to many advances in the detection and treatment of prediabetes and diabetes and the prevention of their related complications. However, there continues to be a distinct gap between these advances and the medical care of patients with diabetes. This article focuses on translational research findings that address the causes of this gap and that attempt to find methods to close this gap at the level of the provider, healthcare system, and patient. The research findings are discussed in terms of elements of the chronic care model originally proposed by Wagner et al. to help optimize the care of patients with any chronic disease such as diabetes. PMID- 22091745 TI - Electrospun fibers with plasmid bFGF polyplex loadings promote skin wound healing in diabetic rats. AB - Deep or chronic skin wounds are difficult to heal spontaneously due to the lack of scaffold to guide cell growth and reduced levels and activities of endogenous growth factors. Emulsion electrospinning process integrated with DNA condensation techniques indicated potentials to gradually release DNA, but no attempt has been made to clarify the advantages in promoting tissue regeneration and wound recovery. In this study, polyplexes of basic fibroblast growth factor-encoding plasmid (pbFGF) with poly(ethylene imine) were incorporated into electrospun fibers with a core-sheath structure, and poly(ethylene glycol) was included into the fiber sheath to allow a sustained release of pbFGF for 4 weeks. In vitro tests on mouse embryo fibroblasts indicated that pbFGF-loaded fibrous mats enhanced cell proliferation by the autocrine bFGF, and an effective cell transfection proceeded for over 28 days. Skin wounds were created in the dorsal area of diabetic rats for in vivo evaluation of skin regeneration after being covered with pbFGF-loaded fibrous mats. The gradual pbFGF release revealed significantly higher wound recovery rate with improved vascularization, enhanced collagen deposition and maturation, complete re-epithelialization and formation of skin appendages. The above results demonstrate the potential use of pbFGF loaded electrospun fibrous mats to accelerate the healing of skin ulcers for patients with diabetic mellitus. PMID- 22091747 TI - Does in vitro fertilisation increase type 2 diabetes and cardiovascular risk? AB - Since the first in-vitro fertilisation (IVF) birth in 1978, the number of children born by assisted reproductive technologies (ART) continues to increase worldwide. However, the safety issues surrounding these procedures remain controversial, and the long term impact on human health is unknown. There is emerging evidence to indicate that IVF may predispose individuals to increased incidence of obesity, elevated blood pressure, fasting glucose and triglycerides and subclinical hypothyroidism. However, few studies have been conducted to date and the underlying mechanisms are unclear. This review will summarize the existing evidence in animal models and in humans, and will discuss epigenetic alterations, which may link manipulation of the pre-implantation embryo with increased risk of the later development of obesity, insulin resistance, type 2 diabetes and cardiovascular disease in offspring. Since these diseases are the leading cause of mortality and can be delayed or prevented by lifestyle modification, prospective follow up studies in IVF born adults are now urgently required to determine the degree of risks utilizing gold standard measures in human and animal models. PMID- 22091748 TI - Diabetes and periodontal diseases: interplay and links. AB - The association between diabetes and periodontal diseases is well-established. Diabetes is a risk factor for periodontal disease, with diabetic patients exhibiting an increased prevalence, extent and severity of gingivitis and perio- dontitis compared to healthy adults. Several mechanisms involved in the pathogenesis of diabetes have also been associated with periodontal disease progression. It is recognized today that there is a bidirectional relationship between diabetes and periodontal disease, with recent research showing that periodontal disease may affect the metabolic control of diabetes in diabetic patients. In this review, we present the current knowledge of the interplay between periodontal diseases and diabetes through the evaluation of randomized control and longitudinal cohort studies published in the past 15 years. Current data support the conclusion that diabetic patients are at increased risk for periodontal diseases, and that patients with poorly controlled diabetes are at risk for severe periodontitis. This results in the destruction of oral connective tissue and generalized bone loss, leading ultimately to tooth loss. Although the effect of periodontal disease on glycemic control in type 1 diabetic patients is controversial, evidence does show a direct correlation between periodontal health and glycemic control in type 2 diabetic patients. Furthermore, several studies have demonstrated the beneficial effect of periodontal treatment on metabolic control of type 2 diabetic patients. PMID- 22091749 TI - Development and mechanistic investigation of a highly efficient iridium(V) silyl complex for the reduction of tertiary amides to amines. AB - The cationic Ir(III) acetone complex (POCOP)Ir(H)(2)(acetone)(+) (POCOP = 2,6 bis(di-tert-butylphosphinito)phenyl) was shown to catalyze the reduction of a variety of tertiary amides to amines using diethylsilane as reductant. Mechanistic studies established that a minor species generated in the reaction, the neutral silyl trihydride Ir(V) complex (POCOP)IrH(3)(SiEt(2)H), was the catalytically active species. High concentrations of this species could be conveniently generated by treatment of readily available (POCOP)IrHCl with tert butoxide in the presence of Et(2)SiH(2) under H(2). Thus, using this mixture in the presence of a trialkylammonium salt, a wide array of tertiary amides, including extremely bulky substrates, are rapidly and quantitatively reduced to tertiary amines under mild conditions with low catalyst loading. A detailed mechanistic study has been carried out and intermediates identified. In brief, (POCOP)IrH(3)(SiEt(2)H) reduces the amide to the hemiaminal silyl ether that, in the presence of a trialkylammonium salt, is ionized to the iminium ion, which is then reduced to the tertiary amine by Et(2)SiH(2). Good functional group compatibility is demonstrated, and a high catalyst stability has provided turnover numbers as high as 10,000. PMID- 22091750 TI - Improving decision-making for feeding options in advanced dementia: a randomized, controlled trial. AB - OBJECTIVES: To test whether a decision aid improves quality of decision-making about feeding options in advanced dementia. DESIGN: Cluster randomized controlled trial. SETTING: Twenty-four nursing homes in North Carolina. PARTICIPANTS: Residents with advanced dementia and feeding problems and their surrogates. INTERVENTION: Intervention surrogates received an audio or print decision aid on feeding options in advanced dementia. Controls received usual care. MEASUREMENTS: Primary outcome was the Decisional Conflict Scale (range: 1-5) measured at 3 months; other main outcomes were surrogate knowledge, frequency of communication with providers, and feeding treatment use. RESULTS: Two hundred fifty-six residents and surrogate decision-makers were recruited. Residents' average age was 85; 67% were Caucasian, and 79% were women. Surrogates' average age was 59; 67% were Caucasian, and 70% were residents' children. The intervention improved knowledge scores (16.8 vs 15.1, P < .001). After 3 months, intervention surrogates had lower Decisional Conflict Scale scores than controls (1.65 vs 1.90, P < .001) and more often discussed feeding options with a healthcare provider (46% vs 33%, P = .04). Residents in the intervention group were more likely to receive a dysphagia diet (89% vs 76%, P = .04) and showed a trend toward greater staff eating assistance (20% vs 10%, P = .08). Tube feeding was rare in both groups even after 9 months (1 intervention vs 3 control, P = .34). CONCLUSION: A decision aid about feeding options in advanced dementia reduced decisional conflict for surrogates and increased their knowledge and communication about feeding options with providers. PMID- 22091751 TI - Laparotomy versus laparoscopy for the treatment of adnexal masses during pregnancy. AB - BACKGROUND: Laparoscopy has been highlighted as an effective surgical modality for diverse pelvic organ diseases. However, its surgical and obstetric efficacy has not been fully confirmed in pregnant women because of the absence of a large comparative study. The objective of this study was to compare outcomes between laparotomy and laparoscopic surgery for adnexal masses during pregnancy. METHODS: A retrospective analysis of 262 pregnant women who underwent laparotomy or laparoscopic surgery for adnexal masses between 2000 and 2009 was performed. RESULTS: Of the 262 women, 174 (66.4%) underwent laparotomy and 88 (33.6%) underwent laparoscopic surgery for adnexal masses. The laparoscopy group had a significantly shorter mean operative time (60.7 +/- 27.1 vs 69.7 +/- 24.4 min, P = 0.002) and mean hospital stay (4.7 +/- 1.7 vs 6.6 +/- 1.3 days, P < 0.001) than the laparotomy group. In multivariate analysis, there was no significant difference between laparoscopy and laparotomy group in obstetric outcomes, including preterm delivery and miscarriage rate, after adjusting for confounding factors, such as gestational age at surgery, emergency surgery and mass size. CONCLUSIONS: The laparoscopic approach appears to offer a suitable alternative to laparotomy, which, in our setting, was associated with shorter operative times and hospital stays than laparotomy. PMID- 22091759 TI - Grouping mechanisms in response preparation investigated with event-related brain potentials. AB - Preliminary information about responses facilitates performance, especially when the information can be grouped into stimulus-response sets, for example, into fingers belonging to the same hand. Here, we studied the mechanisms of supposedly fast and automatic exogenous as compared to slow and controlled endogenous grouping of same-hand fingers. As compared to endogenous cuing, exogenous cuing facilitated reaction times and induced larger amplitudes of the contingent negative variation, but did not show any advantage in amplitude or latency of the lateralized readiness potential or in the magnitude of current source density over the motor cortices. Similarly, the stimulus preceding negativity did not seem to be a plausible explanation for the observed effect. Therefore, at least one functional mechanism underlying exogenous stimulus-response grouping appears to be the facilitation of central response programming. PMID- 22091758 TI - The structure, dynamics, and binding of the LA45 module pair of the low-density lipoprotein receptor suggest an important role for LA4 in ligand release. AB - The low-density lipoprotein receptor (LDLR), the primary receptor for cholesterol uptake, binds ligands through its seven LDL-A modules (LAs). We present nuclear magnetic resonance (NMR) and ligand binding measurements on the fourth and fifth modules of the LDLR (LA45), the modules critical for ApoE binding, at physiological pH. Unlike LA5 and all other modules in LDLR, LA4 has a very weak calcium affinity, which probably plays a critical role in endosomal ligand release. The NMR solution structure of each module in the LA45 pair only showed minor differences compared to the analogous domains in previously determined crystal structures. The 12-residue linker connecting the modules, though slightly structured through an interaction with LA4, is highly flexible. Although no intermodule nuclear Overhauser effects were detected, chemical shift perturbations and backbone dynamics suggest cross talk between the two modules. The ligand affinity of both modules is enhanced when the two are linked. LA4 is more flexible than LA5 and remains so even in the module pair, which likely is related to its weaker calcium binding affinity. PMID- 22091760 TI - State affect and emotion-focused coping: examining correlated change and causality. AB - The purpose of the study was to verify whether two kinds of emotion-focused coping, namely strategies aimed at reducing negative emotions (palliative coping [PC]) and strategies aimed at inducing positive emotions (salutary coping [SC]) are related longitudinally to relevant affective states. Positive and negative state affects were assessed among 133 cardiac patients, along with coping strategies at three time points: a few days after myocardial infarction, one and 6 months later. Due to SC stability, the correlated change with affect was estimated only for PC, but the directionality was examined in all four affect coping pairs. For uncomplementary pairs, the models with diagonal paths equal to zero fitted the data best. For the first complementary pair, i.e., negative affect-PC, reciprocal influences were revealed with both starting points and the amount of decline positively correlated. For the second pair, i.e., positive affect-SC, strategies consequently increased affect, whereas affect decreased SC, but only at first lag. Concluding, PC may be a behavioral manifestation of negative affect rather than reflective goal-oriented efforts. Although the relation between SC and positive affect is more complex, it still supports the idea of distinctiveness within the scope of emotion-focused coping. PMID- 22091761 TI - Aldehyde-alcohol reactions catalyzed under mild conditions by chromium(III) terephthalate metal organic framework (MIL-101) and phosphotungstic acid composites. AB - Porous materials based on chromium(III) terephthalate metal organic frameworks (MIL-101) and their composites with phosphotungstic acid (PTA) were studied as heterogeneous acid catalysts in aldehyde-alcohol reactions exemplified by acetaldehyde-phenol (A-P) condensation and dimethylacetal formation from benzaldehyde and methanol (B-M reaction). The MIL-101 was synthesized solvothermically in water, and the MIL101/PTA composite materials were obtained by either impregnation of the already prepared MIL-101 porous matrix with phosphotungstic acid solution or by solvothermic treatment of aqueous mixtures of Cr(NO(3))(3), and terephthalic and phosphotungstic acids. The MIL101/PTA materials appeared to be effective catalysts for both A-P and B-M reactions occurring at room temperature, with half-lives ranging from 0.5 h (A-P) to 1.5-2 h (B-M) and turnover numbers over 600 for A-P and over 2900 for the B-M reaction, respectively. A synergistic effect of the strong acidic moieties (PTA) addition to mildly acidic Bronsted and Lewis acid cites of the MIL-101 was observed with the MIL101/PTA composites. The ability of the PTA and MIL101/PTA materials to strongly absorb and condense acetaldehyde vapors was discovered, with the MIL101/PTA absorbing over 10-fold its dry weight of acetaldehyde condensate at room temperature. The acetaldehyde was converted rapidly to crotonaldehyde and higher-molecular-weight compounds while in contact with MIL-101 and MIL101/PTA materials. The stability of the MIL-101 and MIL101/PTA catalysts was assessed within four cycles of the 1-day alcohol-aldehyde reactions in terms of the overall catalyst recovery, PTA or Cr content, and reaction rate constants in each cycle. The loss of the catalyst over 4 cycles was approximately 10 wt % for all tested catalysts due to the incomplete recovery and minute dissolution of the components. The reaction rates in all cycles remained unchanged and the catalyst losses stopped after the third cycle. The developed MIL101/PTA composites appear to be feasible for industrial catalytic applications. PMID- 22091762 TI - Population growth, the dependency rate, and the pace of economic development. AB - Abstract The analysis of population's impact on the economy has frequently been developed in the context of the dependency-rate argument. The dependency rate, typically measured as the proportion of the total population outside the labour force, is a summary statistic which is intended to capture the influence of a population's age structure on the process of economic growth. Unfortunately, there has been substantial confusion surrounding the economic interpretation of the dependency rate. This confusion derives from the fact that the dependency rate has been used as a proxy for several age-specific influences of population on economic growth. Additionally, for anyone of these influences of population, the impact on the economy will be determined by the particular economic model within which the dependency rate is being analysed. In other words, depending on which age-specific economic aspect of the dependency rate is being examined, and depending on which economic model forms the basis of the analysis, it is possible that an increase in the dependency rate may be associated with either an increase or a decrease in the economy-wide growth of output per head. As a result, the widely used dependency-rate statistic may not be a particularly useful predictor of economic - demographic - growth-rate interrelationships unless the analyst makes explicit his underlying economic framework, and unless the particular economic influences for which the dependency rate is taken as a proxy are delineated. PMID- 22091763 TI - Population growth: U.S. and Latin American views. AB - Abstract This article is an attempt at interpretation. As one who has worked professionally both in the United States and in Latin America, I would like to interpret how I see the United States and Latin America responding to the high Latin American population growth rate. This is a personal interpretation and as such, of course, is biassed. It is also a very broad subject to which a few pages of interpretation can hardly do justice. The very generalizations 'the United States' and 'Latin America' lend themselves to misunderstanding. These are not homogeneous areas but contain a variety of forces pulling in many directions. And yet, just because this is such a difficult subject as well as such an important one in the world of to-day, it is perhaps worth while to try to distil some common components which may help us gain a better understanding of the actions of others as well as our own. PMID- 22091764 TI - A proposed explanation of the fertility gap differentials by socio-economic status and modernity: The case of Egypt. AB - Abstract The present paper is part of a larger analysis of data collected in the summer of 1970 in the city of Cairo. 1 A joint study between the Institute of Statistical Studies and Research and Centre for Sociological Studies, Cairo. The present analysis is based on a sub-sample of 569 households. PMID- 22091765 TI - Male sterilization as a contraceptive method in Canada an empirical study. AB - Abstract In 1851-61, the crude birth rate in Canada was 45. In 1972, it was approximately 16. Not only have birth rates decreased but the average family size has declined from five or six children per family at the turn of the century to two or three children in the 1970'S. In addition, women are completing their childbearing at an earlier age. 50 years ago, it was not uncommon for a woman to have a child in her late thirties or early forties. To-day, this is a relatively rare event. In fact, it is estimated that approximately 80% of all families have the number of children desired before the woman is 30 years of age. This new demographic pattern creates an important and crucial situation for Canadian couples. At age 30, with all the desired children and 15 more years of potential childbearing ahead of them, what can they do to prevent the occurrence of additional pregnancies? PMID- 22091766 TI - Reproductive time lost due to sexual union dissolution in San Jose, Costa Rica. AB - Abstract It has long been recognized, on a theoretical level, that widowhood, divorce, and separation, if not immediately followed by re-marriage, could have a negative impact on fertility. Davis and Blake specifically identified the amount of reproductive time spent after or between unions as one of the eleven intermediate variables bearing immediately upon fertility. PMID- 22091767 TI - A three parameter model for birth projections. AB - Abstract The approach underlying the model proposed in this article constitutes a considerable departure from the conventional methods used for the projection of birth series. Instead of following the customary procedure of directly projecting the age-specific fertility rates, they can be derived with this model from only three relatively simple fertility measures, namely, total fertility rate, mean age of fertility, and modal age of fertility. The reduction of the number of fertility parameters offers appreciable operational and analytical advantages. Among these, the most significant is the fact that statistical manipulation is confined to only three fertility measures, all of which are particularly appropriate for the in-depth analysis which is required to provide a rationale for assumptions of future fertility. PMID- 22091768 TI - Canada, United States, Australia and New Zealand: Nuptiality trends. AB - Abstract Annual variations are often more brutal for nuptiality than they are for other demographic phenomena. Short-term economic movements, in particular, seem to have a more direct impact. Fig. 1 clearly illustrates this point for Australia during the thirties. Nuptiality rates dip more sharply and recuperation is more pronounced: not only do they follow the employment trend, they amplify it. 1 For nuptiality and fertility, the two indicators we chose are probably the most responsive to short-term movements. They result respectively, from the addition of age-specific first-marriage rates (number of first marriages at age x/total population age x) for ages 15 to 50, and from the combination of parity progression ratios which gives the average number of births per marriage, (a (0)+a (0) a (1)+a (0) a (1) a (2)+ ..., where a (1) is the ratio ofwomen who have a child of order i+1 per 1,000 mothers of children of order i). For each year these were divided by the corresponding cohort index, i.e. the proportion ever married, and the mean number of ever-born children per marriage. The cohort used for a given year is that which reaches its mean age at first marriage in that year or its mean duration at birth of the children. Nine months are subtracted from the fertility measure to give time of conception. The economic indicator is a measure obtained by dividing the number of jobs by the population aged 15 to 64. All indices are calculated using the 1926-1927 figures as base 100. PMID- 22091769 TI - The fecundability of U.S. women. AB - Abstract In this note I shall define fecundability as the probability that a non-pregnant woman will achieve a recognizable pregnancy during a month of exposure to risk. PMID- 22091770 TI - Fertility differentials among the tribal groups of Sierra Leone. AB - Abstract Sierra Leone is in a position typical of many African countries regarding accurate information on her basic demographic characteristics. Such vital registration as exists is confined to a small area and there has been only one census of any reliability, that of 1963. Estimates of fertility levels from the age distribution obtained from that enumeration have been made by Dow, the method having been used previously by Van de Walle for Nigeria. PMID- 22091771 TI - The effect of illegitimacy on U.S. general fertility rates and population growth. AB - Abstract Illegitimacy and bridal pregnancy has attracted the attention of scholars concerned with a variety of plausible causes and consequences ofbirths conceived out of wedlock. Sociologists have expressed concern with the impact of such births on maternal and child health, family stability and the economic status offamilies. Although demographers have described trends in various populations, and have occasionally suggested that births conceived out of wedlock influence general fertility rates and cohort fertility, measures of the demographic impact of illegitimate or premaritally conceived births have not been assessed. While it seems obvious that a change in births conceived out of wedlock will affect change in a general fertility rate, this finding would not automatically allow the conclusion that cohort fertility would change because a change in the rate of births conceived out of wedlock occurred. PMID- 22091772 TI - Mortality decline in the people's Republic of China and the United States. AB - Abstract From mortality levels in 1949 similar to those in the United States during the nineteenth century, China claims to have reduced mortality to levels comparable to those in the United States 30 years ago. The rapidity of this recent transition and its fragmentary statistical verification have made analysts doubt these claims. The purpose of this paper is to assess medical evidence which indicates that the rate of mortality decline has been rapid indeed, primarily due to the unique social organization of Chinese public health practices. PMID- 22091773 TI - Mobility ratios and association in mobility tables. AB - Abstract In the late 1940's a similar problem occurred in the work of three sociologists, working in three countries, on three similar sets of data. Natalie Rogoff, David Glass and G6sta Carlsson all faced the problem of making sense of data on intergenerational occupational mobility. A matrix of frequencies of occupations of respondents by occupations of fathers could be converted, in an obvious and straightforward fashion, into matrices of inflow and outflow percentages. Their joint problem arose in comparing inflow percentages across rows or outflow percentages across columns. The problem was that, as sociologists, concerned with the extent that origins in socially meaningful categories influenced destinations in the same socially meaningful categories, they were stuck with occupational categories that differed from one another dramatically in size. A secondary (though hardly trivial) problem was the fact that, in all their data, the two marginal distributions, the respondents' generation and the fathers' 'generation', were notably dissimilar - a consequence of both differential fertility and a general upward shift in the occupational distributions of the three countries. All sought a technique that would 'make the two time periods comparable with respect to occupational structure'. PMID- 22091777 TI - Fertility effects of the abolition of legal abortion in Romania. PMID- 22091774 TI - A comment on 'social and economic factors in Hong Kong's fertility decline' by Sui-Ying Wat and R. W. Hodge. AB - Abstract The recent article by Wat and Hodge appears to make incorrect inferences about the relation of certain social and economic indicators (infant mortality, employment opportunities for women, and education) to Hong Kong's fertility decline, based on a multiple regression of these variables to the crude birth rate of Hong Kong for 1951-1967. Such modernization measures probably have at least a long-run causal relation to fertility decline. It is also possible that the family planning programme ofHong Kong may have added little to the effects, as the authors suggest. However, I do not believe that their multiple regression analysis establishes these conclusions. PMID- 22091778 TI - Genetic and environmental correlates of topiramate-induced cognitive impairment. AB - Topiramate is an antiepileptic drug that has marked treatment-limiting side effects on specific aspects of cognitive performance in both patients and healthy volunteers. Because these severe side effects occur only in certain individuals, identifying genetic or environmental variables that influence cognitive response would be of great utility in determining whether to administer this drug to a patient. We gave an acute 100 mg oral dose of topiramate to 158 healthy volunteers and measured how the drug changed their performance on a diverse battery of cognitive tests. We found a wide range of responses to topiramate, and we demonstrated that not all tests in the battery were equally affected. There was no correlation between the effect of topiramate and either education level or baseline cognitive performance. Of interest, there was an up to 55-fold variation in the topiramate plasma levels of the participants. Our genome-wide association study (GWAS) of cognitive response did not reveal any genome-wide significant associations; the study was powered to find variants explaining at least 25% of the variation in cognitive response. Combining the results of this GWAS with a retrospective study of cognitive complaints in 290 epilepsy patients who received topiramate as part of their treatment also did not result in a significant association. Our results support the need for additional genetic studies of topiramate that use larger sample sizes. PMID- 22091779 TI - Sexual development and cryptic sexuality in fungi: insights from Aspergillus species. AB - Major insights into sexual development and cryptic sexuality within filamentous fungi have been gained from investigations using Aspergillus species. Here, an overview is first given into sexual morphogenesis in the aspergilli, describing the different types of sexual structures formed and how their production is influenced by a variety of environmental and nutritional factors. It is argued that the formation of cleistothecia and accessory tissues, such as Hulle cells and sclerotia, should be viewed as two independent but co-ordinated developmental pathways. Next, a comprehensive survey of over 75 genes associated with sexual reproduction in the aspergilli is presented, including genes relating to mating and the development of cleistothecia, sclerotia and ascospores. Most of these genes have been identified from studies involving the homothallic Aspergillus nidulans, but an increasing number of studies have now in addition characterized 'sex-related' genes from the heterothallic species Aspergillus fumigatus and Aspergillus flavus. A schematic developmental genetic network is proposed showing the inter-relatedness between these genes. Finally, the discovery of sexual reproduction in certain Aspergillus species that were formerly considered to be strictly asexual is reviewed, and the importance of these findings for cryptic sexuality in the aspergilli as a whole is discussed. PMID- 22091780 TI - Light inhibition of leaf respiration in field-grown Eucalyptus saligna in whole tree chambers under elevated atmospheric CO2 and summer drought. AB - We investigated whether the degree of light inhibition of leaf respiration (R) differs among large Eucalyptus saligna grown in whole-tree chambers and exposed to present and future atmospheric [CO(2) ] and summer drought. Associated with month-to-month changes in temperature were concomitant changes in R in the light (R(light) ) and darkness (R(dark) ), with both processes being more temperature dependent in well-watered trees than under drought. Overall rates of R(light) and R(dark) were not significantly affected by [CO(2) ]. By contrast, overall rates of R(dark) (averaged across both [CO(2) ]) were ca. 25% lower under drought than in well-watered trees. During summer, the degree of light inhibition of leaf R was greater in droughted (ca. 80% inhibition) than well-watered trees (ca. 50% inhibition). Notwithstanding these treatment differences, an overall positive relationship was observed between R(light) and R(dark) when data from all months/treatments were combined (R(2) = 0.8). Variations in R(light) were also positively correlated with rates of Rubisco activity and nitrogen concentration. Light inhibition resulted in a marked decrease in the proportion of light-saturated photosynthesis respired (i.e. reduced R/A(sat) ). Collectively, these results highlight the need to account for light inhibition when assessing impacts of global change drivers on the carbon economy of tree canopies. PMID- 22091782 TI - Electrodermal activity reliably captures physiological differences between wins and losses during gambling on electronic machines. AB - Differential patterns of physiological arousal to win and loss events during gambling is central to psychological conceptualizations of gambling behaviors but is poorly researched. We recorded heart rate (HR) and skin conductance responses (SCRs) to wins and losses while 23 healthy participants played for small incentives on a simulated electronic gambling task. Wins produced large SCRs whereas losses did not, and large wins produced larger SCRs than small wins. Electrodermal measures also correlated with reward responsiveness on a personality measure and with ratings of excitement during gambling. HR evidenced a slight deceleration before event outcomes, and the rebound HR was larger after wins than after losses. The study demonstrates that physiological changes to gambling events can be reliably captured, and that these changes are sensitive to differential outcomes. These findings establish a foundation for future research in field settings. PMID- 22091783 TI - Phylogenetic microarray analysis of a microbial community performing reductive dechlorination at a TCE-contaminated site. AB - A high-density phylogenetic microarray (PhyloChip) was applied to track bacterial and archaeal populations through different phases of remediation at Ft. Lewis, WA, a trichloroethene (TCE)-contaminated groundwater site. Biostimulation with whey, and bioaugmentation with a Dehalococcoides-containing enrichment culture were strategies implemented to enhance dechlorination. As a measure of species richness, over 1300 operational taxonomic units (OTUs) were detected in DNA from groundwater samples extracted during different stages of treatment and in the bioaugmentation culture. In order to determine active members within the community, 16S rRNA from samples were analyzed by microarray and ~600 OTUs identified. A cDNA clone library of the expressed 16S rRNA corroborated the observed diversity and activity of some of the phyla. Principle component analysis of the treatment plot samples revealed that the microbial populations were constantly changing during the course of the study. Dynamic analysis of the archaeal population showed significant increases in methanogens at the later stages of treatment that correlated with increases in methane concentrations of over 2 orders of magnitude. Overall, the PhyloChip analyses in this study have provided insights into the microbial ecology and population dynamics at the TCE contaminated field site useful for understanding the in situ reductive dechlorination processes. PMID- 22091784 TI - Comparison of air-sealing characteristics of tapered- vs. cylindrical-shaped high volume, low-pressure tube cuffs. AB - BACKGROUND: This study aimed at comparing air-sealing characteristics of the new tapered-shaped tracheal tube cuffs with cylindrical tube cuffs. METHODS: Tracheal tubes with tapered-shaped polyurethane (PU) and polyvinyl chloride (PVC) cuffs as well as standard cylindrical-shaped cuffs made of PU and PVC (Covidien, Athlone, Ireland) were investigated. A tracheal model attached to a test lung was intubated, and cuffs were inflated to 10, 15, 20, 25 and 30 cm H(2)O. The test lung was ventilated with intermittent positive pressure ventilation at peak inspiratory pressures (PIPs) of 20 and 25 cm H(2)O. Air leakage was assessed by spirometry and measurement of sevoflurane concentration passing the cuff at the upper cuff border using an anaesthetic gas analyser. Experiments were repeated four times with new tracheal tubes for each run. Statistical comparisons were done using Mann-Whitney U-test with level of significance at P < 0.05. RESULTS: The tapered-shaped PVC tube cuff demonstrated a significantly lower air leakage determined by spirometry than the cylindrical-shaped cuff at both PIPs (20 and 25 cm H(2)O). Similarly, sevoflurane leakage was less with the tapered PVC cuff particularly at higher cuff pressures. With the PU cuff, reduction in air leakage by a tapered-shaped compared with a cylindrical-shaped tube cuff was not significant. CONCLUSIONS: A tapered-shaped tube cuff considerably improves air sealing characteristics of PVC tube cuffs and allows thereby reducing cuff pressure required for sufficient ventilation. In tube cuffs made of PU that exhibits superior sealing characteristics compared with PVC, a tapered shape failed to result in a further reduction of air leakage. PMID- 22091787 TI - Standoffish perhaps, but successful as well: evidence that avoidant attachment can be beneficial in professional tennis and computer science. AB - Attachment-related avoidance and anxiety have repeatedly been associated with poorer adjustment in various social, emotional, and behavioral domains. We examined 2 domains in which avoidant individuals might be better equipped than their less avoidant peers to succeed and be satisfied--professional singles tennis and computer science. These fields may reward self-reliance, independence, and the ability to work without proximal social support from loved ones. In study 1, we followed 58 professional singles tennis players for 16 months and found that scores on attachment-related avoidance predicted a higher ranking, above and beyond the contributions of training and coping resources. In study 2, we sampled 100 students and found that those who scored higher on avoidance were happier with their choice of computer science as a career than those who scored lower on avoidance. Results are discussed in relation to the possible adaptive functions of certain personality characteristics often viewed as undesirable. PMID- 22091785 TI - Ethnic differences in appointment-keeping and implications for the patient centered medical home--findings from the Diabetes Study of Northern California (DISTANCE). AB - OBJECTIVE: To examine ethnic differences in appointment-keeping in a managed care setting. DATA SOURCES/STUDY SETTING: Kaiser Permanente Diabetes Study of Northern California (DISTANCE), 2005-2007, n = 12,957. STUDY DESIGN: Cohort study. Poor appointment-keeping (PAK) was defined as missing >1/3 of planned, primary care appointments. Poisson regression models were used to estimate ethnic-specific relative risks of PAK (adjusting for demographic, socio-economic, health status, and facility effects). DATA COLLECTION/EXTRACTION METHODS: Administrative/electronic health records and survey responses. PRINCIPAL FINDINGS: Poor appointment-keeping rates differed >2-fold across ethnicities: Latinos (12 percent), African Americans (10 percent), Filipinos (7 percent), Caucasians (6 percent), and Asians (5 percent), but also varied by medical center. Receiving >50 percent of outpatient care via same-day appointments was associated with a 4-fold greater PAK rate. PAK was associated with 20, 30, and 40 percent increased risk of elevated HbA1c (>7 percent), low-density lipoprotein (>100 mm/dl), and systolic blood pressure (>130 mmHg), respectively. CONCLUSIONS: Latinos and African Americans were at highest risk of missing planned primary care appointments. PAK was associated with a greater reliance on same-day visits and substantively poorer clinical outcomes. These results have important implications for public health and health plan policy, as primary care rapidly expands toward open access to care supported by the patient-centered medical home model. PMID- 22091788 TI - Methanol and ethylene glycol acute poisonings - predictors of mortality. AB - CONTEXT: Methanol and ethylene glycol cause significant mortality post-ingestion. Predicting prognosis based on the biomarkers osmolal gap, anion gap and pH is beneficial. OBJECTIVE: To evaluate the relationship between biomarkers, measured post-methanol and ethylene glycol exposure, and clinical outcomes. METHODS: A review of the literature identified cases where methanol or ethylene glycol had been ingested and clinical outcomes were recorded. Biomarkers were extracted including osmolal gap, anion gap and pH, with clinical outcomes categorised as recovered, recovered with adverse sequelae and death. Biomarkers were analysed using the Mann-Whitney test for two samples; sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curves. RESULTS: In total, 119 cases of methanol and 88 of ethylene glycol poisoning were identified; 21 methanol and 19 ethylene glycol patients died. For methanol ingestion the mean values, for survival compared to death, were 48 (range: 6-138) and 90 (range: 49 159) mOsm/kg water for osmolal gap (p=0.0052), 31 (range: 11-50) and 41 (range: 30-53) mmol/L for anion gap (p=0.0065) and 7.21 (range: 6.60-7.50) and 6.70 (range: 6.34-7.22) for arterial pH (p<0.0001). The area under the ROC curve was highest for arterial pH, 0.94 (95% CI: 0.89-0.99). For ethylene glycol, these were 49 (range: 0-189) and 79 (range: 25-184) mOsm/kg water for osmolal gap (p=0.050), 28 (range: 6-48) and 38 (range: 20-66) mmol/L for anion gap (p=0.0037) and 7.08 (range: 6.46-7.39) and 6.98 (range: 6.50-7.16) for pH (p=0.072), for survival compared to death. The area under the ROC curve was highest for anion gap, 0.73 (95% CI: 0.60-0.87). CONCLUSION: Post-methanol ingestion a large osmolal gap, anion gap and low pH (<7.22) were associated with increased mortality; and pH has the highest predictive value. Post-ethylene glycol ingestion, both osmolal gap and anion gap were associated with increased mortality. PMID- 22091786 TI - Analgesic conotoxins: block and G protein-coupled receptor modulation of N-type (Ca(V) 2.2) calcium channels. AB - Conotoxins (conopeptides) are small disulfide bonded peptides from the venom of marine cone snails. These peptides target a wide variety of membrane receptors, ion channels and transporters, and have enormous potential for a range of pharmaceutical applications. Structurally related omega-conotoxins bind directly to and selectively inhibit neuronal (N)-type voltage-gated calcium channels (VGCCs) of nociceptive primary afferent neurones. Among these, omega-conotoxin MVIIA (Prialt) is approved by the Food and Drug Administration (FDA) as an alternative intrathecal analgesic for the management of chronic intractable pain, particularly in patients refractory to opioids. A series of newly discovered omega-conotoxins from Conus catus, including CVID-F, are potent and selective antagonists of N-type VGCCs. In spinal cord slices, these peptides reversibly inhibit excitatory synaptic transmission between primary afferents and dorsal horn superficial lamina neurones, and in the rat partial sciatic nerve ligation model of neuropathic pain, significantly reduce allodynic behaviour. Another family of conotoxins, the alpha-conotoxins, are competitive antagonists of mammalian nicotinic acetylcholine receptors (nAChRs). alpha-Conotoxins Vc1.1 and RgIA possess two disulfide bonds and are currently in development as a treatment for neuropathic pain. It was initially proposed that the primary target of these peptides is the alpha9alpha10 neuronal nAChR. Surprisingly, however, alpha conotoxins Vc1.1, RgIA and PeIA more potently inhibit N-type VGCC currents via a GABA(B) GPCR mechanism in rat sensory neurones. This inhibition is largely voltage-independent and involves complex intracellular signalling. Understanding the molecular mechanisms of conotoxin action will lead to new ways to regulate VGCC block and modulation in normal and diseased states of the nervous system. PMID- 22091789 TI - Biomechanical testing of a novel suture pattern for repair of equine tendon lacerations. AB - OBJECTIVE: To compare in vitro biomechanical properties of a novel suture pattern to a current standard for primary repair of equine superficial digital flexor tendon (SDFT) laceration. STUDY DESIGN: In vitro randomized, paired design. ANIMALS: Cadaveric equine forelimb SDFT (n = 24). METHODS: The 3-loop pulley (3LP) and 6-strand Savage (SSS) suture patterns were applied to transected equine SDFT. Ultimate failure load, stiffness, mode of failure, and load required to form a 3-mm gap were obtained using a materials testing system and synchronized high-speed video analysis. Statistical comparisons were made using Student's t test, with significance set at P < .05. RESULTS: The SSS repair failed at a higher ultimate load (421.1 N +/- 47.6) than the 3LP repair (193.7 N +/- 43.0; P < .001). There was no significant difference in stiffness (P = .99). Failure mode was suture breakage for all SSS repair and suture pull through for all 3LP repair. The maximum load to create a 3-mm gap in the SSS repair (102.0 N +/- 22.4) was not significantly different from the 3LP repair (109.9 N +/- 16.0; P = .27). CONCLUSIONS: SSS tenorrhaphy has improved strength and resistance to pull through compared with 3LP for equine SDFT in a single load-to-failure test. Load required to form a 3-mm gap was not significantly different between SSS and 3LP. PMID- 22091790 TI - Testing the effect of function-focused care in assisted living. AB - OBJECTIVES: To develop and test the Function-Focused Care in Assisted Living (FFC AL) intervention so as to alter the decline that older adults in AL experience. DESIGN: Cluster-randomized controlled trial using repeated measures to test the effect of FFC-AL. SETTING: Four AL facilities with at least 100 beds. PARTICIPANTS: One hundred seventy-one residents and 96 direct care workers (DCWs) were recruited. Ninety-five of the DCWs were female (99%), and 59 were black (62%), with a mean age of 41.7 +/- 13.8. The residents were mostly female (80%), white (93%), and widowed (80%), with a mean age of 87.7 +/- 5.7. INTERVENTION: FFC-AL included four components implemented by a research-supported function focused-care nurse (FFCN) and a site-identified champion over a 12-month period. Control sites were exposed to FFC education only. MEASUREMENTS: Outcomes for residents included psychosocial domains (mood, resilience, self-efficacy, and outcome expectations for function and physical activity), function, gait and balance, and actigraphy. Outcomes for DCWs included knowledge, performance, and beliefs associated with FFC. RESULTS: DCWs in treatment sites provided more FFC by 12 months than those in control sites. Residents in treatment sites demonstrated less decline in function, a greater percentage returned to ambulatory status, and there were positive trends demonstrating more time in moderate-level physical activity at 4 months and more overall counts of activity at 12 months than for residents in control sites. CONCLUSION: Using a function focused approach in AL may help prevent some of the functional decline commonly noted in these settings. PMID- 22091791 TI - Purely coherent nonlinear optical response in solution dispersions of graphene sheets. AB - We have developed an efficient chemical exfoliation approach for the high throughput synthesis of solution-processable, high-quality graphene sheets that are noncovalently functionalized by alkylamine. Purely coherent nonlinear optical response of these graphene sheets has been investigated, using near-infrared, visible, and ultraviolet continous wave and ultrafast laser beams. Spatial self phase modulation has been unambiguously observed in the solution dispersions. Our results suggest that this coherent light scattering is due to a broadband, ultrafast, and remarkably huge third-order optical nonlinearity chi(3), which is a manifestation of the graphene's cone-shaped large-energy-scale band structure. Our experimental findings endow graphene new potentials in nonlinear optical applications. PMID- 22091792 TI - Behind-the-counter statins: a silver bullet for reducing costs and increasing access? AB - OBJECTIVE: To examine how the 2004 introduction of behind-the-counter (BTC) simvastatin in the United Kingdom affected utilization, prices, and expenditures. DATA SOURCES/STUDY SETTING: Secondary data on simvastatin utilization, prices, and expenditures between 1997 and 2007 in the United Kingdom and four other countries. STUDY DESIGN: We used a difference-in-differences approach to estimate how the introduction of BTC simvastatin affected utilization, prices, and expenditures. This approach compares outcomes in the United Kingdom before and after the introduction of BTC simvastatin, using outcomes in countries where the drug remained prescription only to control for possible confounders. DATA COLLECTION/EXTRACTION METHODS: Data on simvastain utilization, prices, and expenditures between 1997 and 2007 in the United Kingdom and four other countries were obtained from an outside vendor. PRINCIPAL FINDINGS: The introduction of BTC simvastatin in the United Kingdom led to a significant increase in utilization of simvastatin and a significant decline in expenditures for simvastatin purchases. Our results are robust to alternate model specifications. CONCLUSIONS: Behind-the counter statins have the potential to simultaneously increase use of statins and lower expenditures. PMID- 22091794 TI - Academic geriatrics in Singapore. AB - Singapore is one of the fastest-aging countries in the world. The proportion of adults aged 65 and older is projected to increase from 8.7% to 20% over the next 20 years. The country has developed various strategies to meet the needs of this increase in older adults. There is an acute shortage of geriatricians and a need to train more healthcare workers to care for older adults. Geriatric medicine is a relatively new specialty, and a small number of geriatricians have been tasked with providing an increasing load of clinical service, education, and research. Hence, there is a need to develop a cohesive structure of support for faculty development and retention, advanced specialty trainee recruitment, leadership in medical education, research, and clinical service to care for the rapidly aging population. In addition, geriatric medicine is primarily a hospital-based specialty in Singapore. There is still opportunity to collaborate and improve the academic and practice integration of geriatric medicine into primary care and intermediate and long-term care where it is most needed. PMID- 22091795 TI - The role of meaning-focused coping in significant loss. AB - When individuals face uncontrollable situations such as natural disasters, meaning-focused coping (MFC) can contribute to individuals' adjustment. The objectives of the current study were to examine the role of MFC in post-traumatic growth and to explore how three different types of coping (problem-focused coping, emotion-focused coping, and MFC) affected the mental health of earthquake victims following the 2008 Sichuan Earthquake. Hierarchical regression analyses indicated that MFC had a significantly incremental value in predicting positive affect (DeltaR2=7.6%, p<.01) and well-being (DeltaR2=3.1%, p<.01), above and beyond problem-focused coping and emotion-focused coping. In contrast, for negative affect and depression, these incremental effects were not significant. Path analysis was conducted to test the mediating role of post-traumatic growth among the three coping styles and the outcome variables (well-being, positive affect, negative affect, and depression). The results showed that post-traumatic growth mediated the path from MFC to well-being and positive affect (for positive affect: Sobel z = 3.74, p<.001; for well-being: Sobel z = 5.02, p<.001). In addition, post-traumatic growth mediated the path from problem-focused coping to depression (Sobel z = 2.21, p<.001). The hypothetical model of emotion-focused coping did not converge. PMID- 22091796 TI - Fractional laser resurfacing. PMID- 22091797 TI - Fractional ablative laser skin resurfacing: a review. AB - Ablative laser technology has been in use for many years now. The large side effect profile however has limited its use. Fractional ablative technology is a newer development which combines a lesser side effect profile along with similar efficacy. In this paper we review fractional ablative laser skin resurfacing. PMID- 22091798 TI - Hair removal utilizing the LightSheer Duet HS hand piece and the LightSheer ET: a comparative study of two diode laser systems in Chinese women. AB - OBJECTIVE: To compare the clinical efficacy, safety and pain associated with the use of the LightSheer Duet HS as compared to the original LightSheer ET diode Laser for axillae hair removal in Chinese women. METHODS: Thirty-six Chinese women received three axillae laser hair removal treatments using the LightSheer Duet HS on one side and the LightSheer ET on the other side. Subjects were evaluated for hair removal efficiency. The immediate pain associated with the treatments was noted. RESULTS: At 1 month following the final laser treatment, hair reduction on the LightSheer Duet HS side and on the LightSheer ET side was 81 +/- 13% and 85 +/- 9% respectively. There was no statistical difference. Immediate pain scores at the first session on the LightSheer Duet HS sites and LightSheer ET sites was 5.71 +/- 1.74 and 6.86 +/- 1.80 respectively, which was statistically significant (p < 0.05). Following the second and third sessions, immediate pain scores of the LightSheer Duet HS sites were both less than those of the LightSheer ET sites, but the differences were not statistically significant. CONCLUSIONS: The LightSheer Duet HS laser is a safe and effective method of hair removal in Chinese women. Treatment with the LightSheer Duet HS causes less pain. PMID- 22091799 TI - Clinical efficacy of home-use blue-light therapy for mild-to moderate acne. AB - INTRODUCTION: Blue-light light-emitting diode (LED) therapy has become widely used for the treatment of inflammatory acne. In this study we evaluated the efficacy of a home use blue-light LED application in improving lesions and shortening their time to clearance. METHODS: This was an IRB approved randomized self-control study. For each patient (n = 30), 2 similar lesions, one of each side of the face were chosen for treatment with either a blue-light LED hand-held or sham device. Treatments (n = 4) were conducted twice daily in the clinic and lesions were followed-up till resolution. Reduction in blemishes size and erythema and the overall improvement were evaluated by both the physician and the patients. Time to lesion resolution was recorded. RESULTS: There was a significant difference in the response of lesions to the blue-light LED application as opposed to the placebo in terms of reduction in lesion size and lesion erythema as well as the improvement in the overall skin condition (p < 0.025). Signs of improvement were observed as early as post 2 treatments. Time to resolution was significantly shorter for the blue-light LED therapy. CONCLUSION: The results support the effectiveness of using blue-light LED therapy on a daily basis for better improvement and faster resolution of inflammatory acne lesions. PMID- 22091801 TI - Income inequality and fertility: A comparative view. AB - Summary Most studies pertaining to the relationship between population and economic development suffer from a major flaw. Researchers use aggregate measures like income or energy consumption per head as indicators of economic development. Such aggregate measures fail to take into account the nature of the distribution of income or energy consumption to the population. The present study attempts to demonstrate the importance of incorporating the nature of distribution of resources as an important intervening variable in the study of the overall relationship between population and economic development. A measure of income inequality is developed which represents the difference between rural and urban incomes. This measure is justified in terms of the distinctiveness of urban and rural sectors in the process of development. The data used relate to societal measures of fertility, income, income inequality, etc. Consistently with existing literature, we observe that, generally speaking, economic development does entail a reduction in rural-urban income inequalities. On the other hand, a substantial part of the negative effect of an increase in income per head can be nullified if such an increase were not also accompanied by a reduction in rural-urban income inequality. Also, a substantial part of the negative effect of an increase in income per head and the level of education in reducing the level of infant mortality would be nullified if it did not also result in a reduction of rural urban income inequality. On the other hand, it is quite possible for the level of education in a society to increase together with an increase in income per head without substantially altering the extent of inequality of income between the rural and the urban population. It is suggested that the positive relationship between rural-urban income inequality and the level of fertility is due to higher rural fertility rates in a high-inequality country. By implication, this would mean that higher standards of living for the rural population compared with its urban counterpart will have a favourable impact in reducing rural fertility. PMID- 22091802 TI - Social and demographic determinants of abortion in Poland. AB - Summary Most abortions in Polish hospitals and clinics are performed on social indications. In the 22 administrative areas of Poland, the high rates of divorce and large proportions of total population employed in non-agricultural pursuits reflect the individualistic approach to family planning which is characteristic of present-day urban society. Industrialization is disruptive to the normal functioning of the country's traditionally large families. In addition, the gross reproduction rate increases directly with the proportion of the peasant population in 17 voivodships and five large cities of Poland, whereas in the urban sector the gross reproduction rate has fallen below replacement level in the past few years. Rural birth rates will continue to decline. In view of increasing needs for future manpower, population policy aimed at increasing births through incentives to prospective mothers may achieve a limited degree of success in cities only among the educated segments of the female population. PMID- 22091803 TI - Mortality and fertility in Arctic Communities Greenland - A case study. AB - Summary The purpose of this paper is to estimate the present level of mortality and fertility as well as its history amongst the indigenous population of Greenland during the period 1834-1953 on the basis of a series of censuses taken during that time. Mortality and fertility parameters have been estimated by techniques particularly suited for the analysis of incomplete demographic data - e.g. stable population analysis. During the period studied Greenland was a Danish colony. It did not become constitutionally part of Denmark until 1953. The paper shows that even though the importance of Danish - and other European - influence should not be underestimated, the socio-economic structure of Greenland was relatively stable until 1953. The results show an extremely high mortality and a correspondingly high fertility. There is also evidence that mortality fluctuated considerably during the period. This might also be true of fertility, but it is impossible to establish this by means of the techniques used. These results are supported by an analysis of registrations of births and deaths for part of the period. The paper concludes with an evaluation of the validity of the techniques of estimation, having regard to the nature of the Greenland censuses. It is pointed out that the empirical material from which model stable populations must have been constructed varies somewhat from that applicable to an Arctic population. PMID- 22091804 TI - Government policy and personal family planning approval in conflict settings: The case of the Muslim minority in the Southern Philippines. AB - Summary Certain minority groups in a number of culturally pluralistic societies have interpreted governmentally sponsored family planning programmes as vehicles for reducing one basis for potential political power, i.e. the minority group's share of the total population. This has especially been the case in societies with protracted inter-group conflict. Such a conflict situation is found in the Southern Philippines between indigenous Muslims and arriving Christian settlers. Contrasting Muslim women in predominantly Muslim and in pluralistic-Muslim minority settings into which there have been sizeable Christian incursions, we suggest that though cultural pluralism has facilitated the dissemination of the national government's position on family planning, the nature of culture contact, and inter-group conflict could have provoked personal opposition to family planning because of its links with the government. PMID- 22091805 TI - Factors associated with the timing and duration of the leaving-home stage of the family life cycle. AB - Summary Based on empirical age distributions of sons and daughters leaving home, an examination is made of the theoretical effect of three factors - the sex composition of the family, the interval between births, and their reasons for leaving home - on the dynamics of the leaving-home stage in the life cycle of two child families. Consideration is given to four measures, the timing of the beginning and end of the leaving-home stage, its duration, and the ratio of the length of the leaving-home stage to the length of the childbearing stage. The outstanding feature of the leaving-home stage is that a second child may leave home before its older sibling, described as the 'crossing-over effect'. For Australian data, factors contributing to the variation in experience between families include the fact that sons generally leave home at an older age than daughters, and that children leaving home for different reasons leave at different ages. Brief reference is made to the relationship between the leaving home stage and the starting-work stage, and to the limitations of a theoretical analysis. PMID- 22091806 TI - The role of simulation techniques in the theory and observation of family formation. AB - Summary The investigation of fertility change can involve the consideration of the results of micro-level empirical studies in the context of an economic theory of family formation. In particular, a change in the observable statistics can then be related to a change in behaviour, or factors influencing behaviour. The analysis of this relationship is hindered, however, by its complexity and by the large number of stochastic variables present. It is argued that an essential aid to such an analysis is the use of a model suitable for simulation. Here, we present such a model and illustrate possible applications with various experiments. PMID- 22091807 TI - A re-estimation of the multiplying factors for the Brass technique for determining childhood survivorship rates. AB - Summary One of the truly significant contributions to practical demography is the procedure developed by William Brass for estimating life-table values from minimal data obtained in fertility surveys. Specifically, Brass designed a set of factors dependent on the shape of the fertility schedule, which convert proportions of children dead of women in standard age intervals into life table q(x)-values. Jeremiah Sullivan recently presented in this journal a method for simplifying the calculations involved in obtaining the multiplying factor in the Brass procedure. Both Brass and Sullivan employed restrictive fertility schedules to obtain their multiplying factors, and a rigorous test of either model has been hampered by the lack of numerous adequately recorded fertility schedules, especially those which begin early. Recently, a set of model fertility schedules which adequately duplicates empirical fertility schedules has been developed. These schedules were used to test the Brass and Sullivan procedures and to obtain new estimates of multiplying factors. Although the Brass and Sullivan procedures are shown to produce good estimators, new estimators, which prove superior to either, are developed and analysed. PMID- 22091808 TI - The mixed effects of income upon successive births may explain the convergence phenomenon. AB - Summary This paper finds that an increment of income has a more positive (less negative) effect on the probability of a family having another child when it consists of relatively few children than of relatively many children. That is, within a group of people whose income is increased, the increase may be expected to influence the average family with no children or one child to increase family size, and to influence the average family that would otherwise have many children to have fewer. To put it another way, increased income reduces the variance of family size across families. This provides an explanation for the 'convergence' of American families to two to four children. The basis for these conclusions is a cross-sectional analysis of white women in the U.S. Census of 1960. PMID- 22091809 TI - The impact of children on household saving: Age effects versus family size. AB - Summary This paper extends a recent article by Allen Kelley, 'Population Growth, the Dependency Rate, and the Pace of Economic Development', published in Population Studies, 27, 3. Its objectives are threefold: (1) to point out that Kelley's earlier assessment of the effect of family size on household savings rates turns on somewhat arbitrary methods of computation and is altered when more conventional procedures are used, (2) to argue that in modern American society the savings behaviour of families may be tied more to the ages of the children than to their number, and (3) to provide some comparative evidence which tends to substantiate Kelley's conjecture that the way and extent to which children influence household savings patterns depends upon the underlying level of economic development. PMID- 22091810 TI - Reliability estimates of some survey data on family planning. AB - Summary A follow-up study employing the panel design which aimed to evaluate the temporal stability of rural respondents' answers to KAP and fertility-related questions after a lapse of nearly five months revealed that reports by females on factual data dealing with socio-economic and demographic topics are as highly reliable as are those of males. The study based on 79 males and 81 females in Haryana further supports the hypothesis that re-test reliabilities of factual data such as respondent's age, religion, occupation, etc. are substantially higher than those of knowledge about contraceptives. Attitude items showed very low re-test reliabilities although the internal consistency reliabilities of the two attitude scales were found to vary within the range of 0.72 to 0.88. Both attitude scales were found to have a very high reproducibility coefficient, all higher than 0.95, for both the interview sessions. Re-test reliabilities of data on contraceptive use were also found to be moderately high. However, the rates of loop insertion and condom use as reported by female respondents are likely to show a substantial amount of gross error as is evident from their low re-test reliabilities. The findings of the present study cast serious doubt on the assumption that married males are not capable of accurately reporting the pregnancy histories of their wives. Several implications of the findings are discussed. From the methodological point of view they suggest a need to develop improved techniques for assessing attitudes toward family planning programmes and abortion as well as to knowledge of contraceptive methods and desired family size. The findings also justify the inclusion of eligible male respondents in KAP and fertility surveys. PMID- 22091811 TI - A note on nineteenth-century Irish emigration statistics. AB - Summary On the basis of a re-examination of the different statistical series of post-Famine Irish emigration, this paper finds (1) that the total outflow was larger than the figures for total emigration allow, and (2) that permanent movement to Great Britain was substantially more important, both relatively and absolutely, than is commonly realized. PMID- 22091812 TI - Tribal affiliation and fertility: A note. AB - Summary This not extends T. L. F. Devis's recent investigation of the relationship between tribal affiliation and fertility in Sierra Leone. Controls are introduced for age structure and economic variables. The findings suggest that tribal affiliation does not have much independent influence on fertility after these factors are allowed for. PMID- 22091815 TI - Erratum. PMID- 22091816 TI - Ventricular enlargement in new-onset pediatric epilepsies. AB - PURPOSE: To examine baseline and prospective (2-year) changes in third, fourth, and lateral ventricle volumes in children with new-onset idiopathic epilepsies and controls (age 8-18 years). METHODS: Structural magnetic resonance imaging (MRI) were collected from children with idiopathic generalized epilepsy (IGE, n = 29), idiopathic localization-related epilepsy (ILRE, n = 30), and healthy controls (HCs, n = 49). Volumes of the third, fourth, and lateral ventricles were derived and compared across groups, followed by shape analyses, to identify specific regions of ventricular abnormality. Of the initial cohort, a consecutive sample of 71 children returned 2 years later for reimaging and determination of progressive changes in the ventricular system. KEY FINDINGS: At baseline, children with new-onset IGE had significantly larger lateral and third ventricle volumes relative to the HC group. In addition, lateral ventricle enlargement in IGE was significantly greater compared to new-onset ILRE. Shape analysis of the lateral ventricles revealed that volume expansion in IGE was selective for the anterior horn, a region surrounded by the lateral and medial frontal lobes as well as basal ganglia. These abnormalities did not progress over a 2-year interval. SIGNIFICANCE: Abnormalities in brain development prior to onset and diagnosis of epilepsy are evident and reflected in expansion of the ventricular system, especially among children with IGE. These abnormalities appear to represent an antecedent and possibly static finding given the lack of progressive ventricular expansion over the 2-year interval following diagnosis and treatment. PMID- 22091818 TI - Structure-activity relationships in the control of chemical risks. PMID- 22091819 TI - Predictions for existing chemicals-a multilateral QSAR project. AB - Abstract Following a previous collaborative EU/EPA project focussed on QSAR predictions for a selection of new chemicals which had been notified in the EU, a similar exercise was started in 1993 on existing chemicals. In a first phase, the project addresses the High Production Volume (HPV) chemicals which are produced or imported at levels above a 1000t/year in the EU and 454t/year in the US. The relevant EU (Annex 1 of Existing Chemicals Regulation No. 793/93) and US-EPA lists contain 1036 and 2881 organic substances respectively of which HPV 749 chemicals are in common. The joint project aims at an estimation through validated QSAR models of the physical-chemical, ecotoxicity and toxicity endpoints which are included in the regulation and where experimental data will become available in IUCLID (International Unified Chemicals Information Database). Next to EC-JRC (ECB) and US-EPA, various laboratories in the EU are contributing to the project and recently, two institutes in Japan have joined in this project. PMID- 22091817 TI - Crotonase catalysis enables flexible production of functionalized prolines and carbapenams. AB - The biocatalytic versatility of wildtype and engineered carboxymethylproline synthases (CMPSs) is demonstrated by the preparation of functionalized 5 carboxymethylproline derivatives methylated at C-2, C-3, C-4, or C-5 of the proline ring from appropriately substituted amino acid aldehydes and malonyl coenzyme A. Notably, compounds with a quaternary center (at C-2 or C-5) were prepared in a stereoselective fashion by engineered CMPSs. The substituted-5 carboxymethyl-prolines were converted into the corresponding bicyclic beta lactams using a carbapenam synthetase. The results demonstrate the utility of the crotonase superfamily enzymes for stereoselective biocatalysis, the amenability of carbapenem biosynthesis pathways to engineering for the production of new bicyclic beta-lactam derivatives, and the potential of engineered biocatalysts for the production of quaternary centers. PMID- 22091820 TI - Assessment of QSARS for Predicting Fate and Effects of Chemicals in the Environment: An International European Project. AB - Abstract In 1993, an international project on QSAR has been started with funding from the Commission of the European Union. The first part of the project is focused on preparing an overview of existing models for the prediction of environmental parameters such as bioconcentration, sorption, degradation and ecotoxicity. Emphasis will be given to defining the limitations of the models. Since all models, including QSARs, have their limitations, it is important that these limitations are known in case QSARs are actually used and applied within the risk assessment context. The second part of the project is directed towards experimental research on new developments with emphasis on the use of multivariate techniques and quantum chemical properties. In this short paper, a general outline of the project will be given, as well as some first results. Results of experimental work within this project will be published in the proceedings of the 6th International Workshop on QSAR in Environmental Sciences and will appear in this same journal. PMID- 22091821 TI - Evaluation of the Use of QSARS for Priority Setting and Risk Assessment. AB - Abstract Impending changes in EEC legislation have accelerated the need to define the principles and practical considerations of the use of QSARs in priority setting and risk assessment. It is important to delineate the limitations of this approach and to review whether and how this information should be used in the risk assessment. The value and limitations of QSARs for use in priority setting and risk assessment will not be discussed in detail since the European Chemical Industry Ecology and Toxicology Centre (ECETOC) has only recently established a Task Force to tackle this issue. The terms of reference of the Task Force are: (1) compare the predictions obtained with QSARs to measured data using ECETOC databases and other sources of data and comment on the validity and applicability of such QSARs; (2) identify and review software packages which are available for accessing and using appropriate QSARs; (3) identify those aspects of environmental distribution, fate and effects where the further development of QSARs is desirable and feasible; and (4) provide a scientific basis for ECETOC's contribution to the activities of the European Chemicals Bureau (ECB) in this area. In this short paper, only an initial and personal evaluation is made of when and where to use QSARs in the priority setting and risk assessment process within the regulatory framework. Some critical remarks and suggestions are provided to guide future developments and integration of QSARs in the risk assessment process. PMID- 22091822 TI - Editorial board page for "SAR and QSAR in Environmental Research", Volume 3, Number 3. AB - Abstract This is a scanned image of the original Editorial Board page(s) for this issue. PMID- 22091823 TI - Decoding Caulobacter development. AB - Caulobacter crescentus uses a multi-layered system of oscillating regulators to program different developmental fates into each daughter cell at division. This is achieved by superimposing gene expression, subcellular localization, phosphorylation, and regulated proteolysis to form a complex regulatory network that integrates chromosome replication, segregation, polar differentiation, and cytokinesis. In this review, we outline the current state of research in the field of Caulobacter development, emphasizing new findings that elaborate how the developmental program is modulated by factors such as the environment or the metabolic state of the cell. PMID- 22091824 TI - The influence of the magnitude, probability, and valence of potential wins and losses on the amplitude of the feedback negativity. AB - We assessed the influence of the variables outcome potential, feedback valence, magnitude, and probability on the amplitude of the feedback negativity (FN). Outcome potential was defined as the a priori valence of an upcoming feedback, that is, is there a potential win or potential loss? All these variables have been studied previously, although never together, but the findings have been contradictory. We analyzed the event-related potential (ERP) after feedback presentation in a reinforcement-learning task to examine the effects of all the variables on feedback negativity. Our results show that outcome potential, feedback valence, probability, and magnitude all influence feedback related ERPs. Taken together, the findings suggest that ERPs in the time range of the feedback negativity are primarily driven by positive outcomes (reinforcement) rather than negative outcomes (punishment). PMID- 22091825 TI - "Does this doctor speak my language?" Improving the characterization of physician non-English language skills. AB - OBJECTIVE: To describe the initial impact of an organizational policy change on measurement of physician non-English language proficiency. STUDY SETTING: Multispecialty health care organization in the San Francisco Bay Area. STUDY DESIGN/DATA COLLECTION: In response to preliminary findings suggesting that the organization's nonvalidated and undefined three-category tool for physician self report of non-English language proficiency levels was likely inadequate, the organization asked physicians to rate their non-English language proficiency levels using an adapted Interagency Language Roundtable (ILR) scale, a validated measure with five rating levels and descriptors. We then compared the self reported language proficiency on the original scale and the ILR for those physicians who completed both and used regression analysis to investigate physician characteristics potentially associated with a change in score on the old versus ILR scales. PRINCIPAL FINDINGS: Six months after the ILR scale was implemented throughout the organization, 75 percent (258/342) of physicians had updated their language proficiency ratings. Among clinicians who had previously rated themselves in the "Medical/Conversational" category, there were substantial variations in scores using the ILR scale. Physicians who spoke two or more non English languages were significantly more likely to lower their self-reported proficiency when updating from the old scale to the ILR scale. CONCLUSIONS: The organization was willing to adopt a relatively straightforward change in how data were collected and presented to patients based on the face validity of initial findings. This organizational policy change appeared to improve how self-reported physician language proficiency was characterized. PMID- 22091826 TI - Mortality in out-of-hospital cardiac arrest patients has decreased in the era of therapeutic hypothermia. AB - BACKGROUND: Mild therapeutic hypothermia (TH) improves survival after out-of hospital cardiac arrest (OHCA). This treatment was implemented in most Finnish intensive care units (ICUs) in 2003. The aim of this study was to find out whether hospital mortality of ICU-treated OHCA patients has changed in the era of TH. METHODS: This was a retrospective study of data collected prospectively into the database of the Finnish Intensive Care Consortium during the years 2000-2008. The study population consisted of 3958 patients for whom cardiac arrest was registered as the reason for ICU admission and who were transferred to the ICU from the emergency department. We divided the patients into those treated in the pre-hypothermia era (2000-2002) and those treated in the hypothermia era (2003 2008). We investigated whether the treatment period had any impact on hospital mortality. RESULTS: There were no differences between the periods regarding the age or initial Glasgow Coma Scores of the patients. Mean severity of illness was higher in the latter period. Despite this, mortality decreased: the hospital mortality rate was 57.9% in 2000-2002 and 51.1% in 2003-2008, P < 0.001. In a multivariate logistic regression analysis, treatment in 2003-2008 was associated with a reduced risk of in-hospital death (adjusted odds ratio 0.54, 95% confidence interval 0.45-0.64 and P < 0.001). Survival improved markedly between the years 2002 and 2003. This improvement has persisted, but there has been no further improvement. CONCLUSION: Concurrently with the implementation of TH, hospital mortality of OHCA patients treated in Finnish ICUs decreased. PMID- 22091827 TI - When doctors and daughters disagree: twenty-two days and two blinks of an eye. AB - A cornerstone of American medical ethics is the right to say, "Keep your hands off of me," to decline medical treatment. A central problem is how to decide about individuals who have become incapacitated and can no longer request or refuse potentially life-sustaining treatment. An advance directive is a formal attempt to protect people's right to autonomy when they are no longer autonomous. As such, it assumes that previously expressed wishes are precise and immutable, but many families make decisions together, and individuals may negotiate, compromise, and modify their genuine preferences, especially when novel threats arise, and the stakes are high. The current article describes a case in which two daughters overruled a patient's explicit preference to refuse life-sustaining treatment, leading to burdensome illness before death. In the end, the mother seemed to understand her children's needs and seemed willing, at least in retrospect, to have met those needs. After the death of this individual, we continued to talk with the daughters and videotaped an interview in which they shared their perspectives on the case. The daughters consented to be videotaped and to share the video with the medical community (available in online version of article). Their forceful devotion to their mother and their search in retrospect for what could have been done differently has completely changed our understanding of events. We believe that the daughters' behavior is not the indefensible breach of respect for person that it seemed to be. Their mother's true wishes might well have included a desire to help her children during her own dying. Family members' preferences are likely to be important considerations for many people, although the possibility of coercion has to be acknowledged as well. Accommodating this level of decision-making complexity is highly problematic for our understanding of advance directives. PMID- 22091828 TI - Development and field-scale optimization of a honeycomb zeolite rotor concentrator/recuperative oxidizer for the abatement of volatile organic carbons from semiconductor industry. AB - The combined concentrator/oxidizer system has been proposed as an effective physical-chemical option and proven to be a viable solution that enables Volatile Organic Carbons (VOCs) emitters to comply with the regulations. In this work, a field scale honeycomb zeolite rotor concentrator combined with a recuperative oxidizer was developed and applied for the treatment of the VOC waste gas. The research shows the following: (1) for the adsorption rotor, zeolite is a more appropriate material than Granular Activated Carbon (GAC). The designing and operation parameters of the concentrator were discussed in detail including the size and the optimal rotation speed of rotor. Also the developed rotor performance's was evaluated in the field; (2) Direct Fired Thermal Oxidizer (DFTO), Recuperative Oxidizer (RO), Regenerative Thermal Oxidizer (RTO) and Regenerative Catalytic oxidizer (RCO) are the available incinerators and the RO was selected as the oxidizer in this work; (3) The overall performance of the developed rotor/oxidizer was explored in a field scale under varying conditions; (4) The energy saving strategy was fulfilled by reducing heat loss from the oxidizer and recovering heat from the exhaust gas. Data shows that the developed rotor/oxidizer could remove over 95% VOCs with reasonable cost and this could be helpful for similar plants when considering VOC abatement. PMID- 22091829 TI - The hierarchical structure of childhood personality in five countries: continuity from early childhood to early adolescence. AB - Childhood personality is a rapidly growing area of investigation within individual differences research. One understudied topic is the universality of the hierarchical structure of childhood personality. In the present investigation, parents rated the personality characteristics of 3,751 children from 5 countries and 4 age groups. The hierarchical structure of childhood personality was examined for 1-, 2-, 3-, 4-, and 5-factor models across country (Canada, China, Greece, Russia, and the United States) and age group (3-5, 6-8, 9 11, and 12-14 years of age). Many similarities were noted across both country and age. The Five-Factor Model was salient beginning in early childhood (ages 3-5). Deviations across groups and from adult findings are noted, including the prominent role of antagonism in childhood personality and the high covariation between Conscientiousness and intellect. Future directions, including the need for more explicit attempts to merge temperament and personality models, are discussed. PMID- 22091830 TI - Novel blockers of hyperpolarization-activated current with isoform selectivity in recombinant cells and native tissue. AB - BACKGROUND AND PURPOSE Selective hyperpolarization activated, cyclic nucleotide gated channel (HCN) blockers represent an important therapeutic goal due to the wide distribution and multiple functions of these proteins, representing the molecular correlate of f- and h-current (I(f) or I(h) ). Recently, new compounds able to block differentially the homomeric HCN isoforms expressed in HEK293 have been synthesized. In the present work, the electrophysiological and pharmacological properties of these new HCN blockers were characterized and their activities evaluated on native channels. EXPERIMENTAL APPROACH HEK293 cells expressing mHCN1, mHCN2 and hHCN4 isoforms were used to verify channel blockade. Selected compounds were tested on native guinea pig sinoatrial node cells and neurons from mouse dorsal root ganglion (DRG) by patch-clamp recordings and on dog Purkinje fibres by intracellular recordings. KEY RESULTS In HEK293 cells, EC18 was found to be significantly selective for HCN4 and MEL57A for HCN1 at physiological membrane potential. When tested on guinea pig sinoatrial node cells, EC18 (10 uM) maintained its activity, reducing I(f) by 67% at -120 mV, while MEL57A (3 uM) reduced I(f) by 18%. In contrast, in mouse DRG neurons, only MEL57A (30 and 100 uM) significantly reduced I(h) by 60% at -80 mV. In dog cardiac Purkinje fibres, EC18, but not MEL57A, reduced the amplitude and slowed the slope of the spontaneous diastolic depolarization. CONCLUSIONS Our results have identified novel and highly selective HCN isoform blockers, EC18 and MEL57A; the selectivity found in recombinant system was maintained in various tissues expressing different HCN isoforms. PMID- 22091831 TI - Computed tomographic documentation of the natural progression of humeral intracondylar fissure in a cocker spaniel. AB - OBJECTIVE: To report the computed tomographic (CT) documentation of humeral intracondylar fissure (HIF) developing after complete ossification of the humeral condyle (HC). STUDY DESIGN: Clinical report. ANIMALS: Male 3 year old working (English) Cocker Spaniel. METHODS: Sequential CT screening (659-day interval between analyses). RESULTS: A sagittal hypodense fissure typical of incomplete ossification of the humeral condyle (IOHC) was identified ~ 22 months after screening CT examination documented a normal elbow joint. CONCLUSION: Even in dogs with clinical features typical of the condition most commonly termed IOHC, fissure formation and propagation can occur after ossification is complete. PMID- 22091832 TI - Repair of rabbit ulna segmental bone defect using freshly isolated adipose derived stromal vascular fraction. AB - BACKGROUND AIMS: Stromal vascular fractions (SVF) from adipose tissue have heterogeneous cell populations, and include multipotent adipose-derived stem cells. The advantages of using of SVF include the avoidance of an additional culture period, a reduced risk of extensive cell contamination, and cost effectiveness. METHODS: Unilateral 20-mm mid-diaphyseal segmental defects in rabbit ulna were treated with one of the following: polylactic glycolic acid (PLGA) scaffold alone (group 1, control), a PLGA scaffold with undifferentiated SVF cells (group 2), or a PLGA scaffold with osteogenically differentiated SVF cells (group 3). At 8 weeks after implantation, five rabbits in each treatment group were killed to assess bone defect healing by plain radiography, quantitative microcomputed tomography and histology. RESULTS: The SVF cells were well grown on PLGA scaffolds and expressed type I collagen and alkaline phosphatase (ALP). The intensity of ALP and OPN gene expressions in osteogenic medium culture were increased from 14 days to 28 days. In vivo evaluations at 8 weeks showed that treatment of SVF cells with or without osteogenic differentiation resulted in more bone formation in the critically sized segmental defects than PLGA scaffold alone. Osteogenically differentiated SVF cells significantly enhanced bone healing compared with undifferentiated SVF cells. CONCLUSIONS: Adipose-derived stromal SVF showed osteogenic potential in vitro. Accordingly, SVF could provide a cell source for bone tissue engineering. However, treatment with uncultured SVF cells on bone healing was not satisfactory in the in vivo animal model. PMID- 22091833 TI - Comparison of chemokine and receptor gene expression between Wharton's jelly and bone marrow-derived mesenchymal stromal cells. AB - BACKGROUND AIMS: Because of their multilineage differentiation capacity, immunomodulatory role and homing ability, mesenchymal stromal cells (MSC) are emerging as a new therapeutic strategy for treating a variety of disorders. Although bone marrow (BM) is the best characterized source of MSC, Wharton's jelly (WJ) of the umbilical cord holds great promise as an alternative. As delivery direct to the site of injury is not always feasible, efficient homing of MSC to the site of injury is critical for inducing tissue repair and regeneration. MSC express a wide variety of growth factors, chemokines and receptors that are important for cell migration, homing and re-establishment of blood supply for recovery of damaged tissues. METHODS: Detailed chemokine and receptor gene expression profiles of WJ MSC were established, and subsequently compared with those of BM-derived MSC using a polymerase chain reaction (PCR) array. Secretion of growth factors was analyzed and evaluated using culture supernatant from WJ and BM MSC. RESULTS: Our results revealed a differential expression pattern of the chemokines and their receptors between WJ- and BM derived MSC. Several Glutamic acid-Leucine-Arginine; ELR-positive CXC chemokine genes and secretion of growth factors, which promote angiogenesis, were found to be up-regulated in WJ MSC. CONCLUSIONS: To understand better the localization and mechanism of tissue repair by transplanted WJ MSC, we attempted chemokine and their receptor transcription profiling, followed by analysis of growth factors secreted by WJ MSC, and compared them against those of BM MSC. The data suggest that MSC from different sources can be explored for distinct therapeutic roles. PMID- 22091835 TI - The feedback-related negativity (FRN) in adolescents. AB - This study examined age-related differences in the ERP correlates of external feedback processing (i.e., the feedback-related negativity [FRN]) in adolescent and young adult males, using a simple gambling task involving unpredictable monetary losses and gains of low and high magnitude. The FRN was larger after losses than gains, and was modulated by the magnitude of gains, but not the magnitude of losses, for all participants regardless of age. FRN amplitude was larger in adolescents than adults and also discriminated relatively less strongly between gains and losses in adolescents. In addition, the morphology of the waveform after high losses suggests that feedback in this condition may have been processed less efficiently by adolescents. Our results suggest that, although the FRN in adults and adolescents share some common characteristics, the neural processes that generate the FRN are still developing in midadolescence. These findings are discussed in the context of adolescent risk taking. PMID- 22091834 TI - Can claims-based data be used to recruit black and Hispanic subjects into clinical trials? AB - OBJECTIVE: Evaluate the accuracy of an algorithm at identifying ethnic minorities from administrative claims for enrollment into a clinical trial. DATA SOURCES/STUDY SETTING: Claims data from a health benefits company. STUDY DESIGN: We compared results of a three-step algorithm to self-reported race/ethnicity. DATA COLLECTION/EXTRACTION METHODS: Using the algorithm, we identified subjects with high probability of being minority and ascertained self-reported race/ethnicity. PRINCIPAL FINDINGS: We identified 164 subjects as likely minority based on our algorithm. Of these, 94 completed the survey and 87 identified themselves as black or Hispanic. The positive predictive value of the algorithm was 93 percent (CI: 85-97). CONCLUSIONS: Claims data can be used to efficiently identify minorities for participation in clinical trials. PMID- 22091836 TI - NHC gold halide complexes derived from 4,5-diarylimidazoles: synthesis, structural analysis, and pharmacological investigations as potential antitumor agents. AB - A series of novel neutral NHC gold halide complexes derived from 4,5 diarylimidazoles were synthesized, characterized, and analyzed for biological effects. High growth inhibitory effects in MCF-7 and MDA-MB 231 breast cancer as well as HT-29 colon cancer cell lines depended on the presence of the C4,C5 standing aromatic rings. Methoxy groups at these rings did not change the growth inhibitory properties, while F-substituents in the ortho-position (5d) increased the activity in MCF-7 and MDA-MB 231 cells. The substituents at the nitrogen atoms and the oxidation state of the metal play a subordinate role. The most active bromo[1,3-diethyl-4,5-bis(2-fluorophenyl)-1,3-dihydro-2H-imidazol-2 ylidene]gold(I) (5d) was distinctly more active than cisplatin. All complexes caused thioredoxin reductase (TrxR) inhibition (EC50=374-1505 nM) distinctly lower than auranofin (EC50=18.6 nM) excluding this enzyme as main target. Because of the low nuclear content, a participation of DNA interaction on the mode of action is very unlikely. The missing ER binding and the missing correlation of growth inhibition and inactivation of COX enzymes exclude these targets, too. PMID- 22091837 TI - Autism spectrum disorders in older adults: toward defining a research agenda. AB - Autism spectrum disorders (ASDs) are among the most common of the severe developmental disabilities, yet little is known about older adults with ASDs-in particular, how the disabilities and dependencies that result from aging interact with those resulting from ASDs. The aging of the population in Western countries, the increasing rate of diagnosis of ASDs, and the burgeoning use of services for ASDs are converging to create a large, growing influx of older adults with ASDs that could impose tremendous humanistic and economic burdens on the healthcare system and society. An understanding of the epidemiological, biological, psychological, and social aspects of ASDs in older adults is essential for preparing to meet their needs, but studies on ASDs in these individuals are practically nonexistent. This article outlines observations and recommendations of a multidisciplinary expert group convened in March 2010 to characterize gaps in knowledge regarding ASDs in older adults and defines research directions to help individuals, the healthcare system, and society prepare for meeting the needs of this population. The proposed research agenda could help improve the lives of older adults with ASDs and inform research and clinical practice involving younger individuals with ASDs. PMID- 22091838 TI - The relationship between retrieval-induced forgetting, anxiety, and personality. AB - Retrieval-induced forgetting (RIF) refers to the finding that the retrieval of a memory trace suppresses the retrieval of rival memory traces, and there is evidence that RIF reflects the effects of cognitive inhibition. The Attentional Control Theory (ACT) postulates that cognitive inhibition will be impaired by a high level of state anxiety, but the effect of anxiety on RIF has not previously been investigated. A sample of 116 participants were tested on the RIF procedure, and were also administered the Spielberger State Anxiety Inventory and the Big Five Personality Inventory. The results indicated a significant negative correlation between RIF scores and state anxiety, and a significant positive correlation between RIF scores and extraversion. However, a multiple regression analysis identified extraversion as the main predictor of RIF performance. None of the other personality factors correlated with RIF scores. These findings are consistent with the predictions of the ACT. PMID- 22091841 TI - An Investigation of Clustering as a Tool in Quantitative Structure-Activity Relationships (QSARS). AB - Abstract By means of clustering, one is able to manage large databases easily. Clustering according to structure similarity distinguished the several chemical classes that were present in our training set. All the clusters showed correlation of log WS with log K ( OW ) and melting point, except EINECS-cluster 1. This cluster contains only chemicals with melting points below room temperature, resulting in a log WS-log K( OW ), relationship. The observed weak correlation for this cluster is probably due to the insufficient number of available screens. Such a limited amount of screens allows relatively very different chemicals to share the same cluster. Using statistical criteria, our approach resulted in three QSARs with reasonably good predictive capabilities, originating from clusters 1639, 3472, and 5830. The models resulting from the smaller clusters 6873, 8154, and 16424 are characterised by high correlation coefficients which describe the cluster itself very well but, due to our stringent bootstrap criterion, they are close to randomness. Clusters 6815 and 18083 showed rather low correlations. The models originating from clusters 1639, 3472, and 5830 proved their usefulness by external validation. The log WS-values calculated with our QSARs agreed within 1 log-unit to these reported in the literature. PMID- 22091840 TI - Prostaglandin E(2) potentiates methylmalonate-induced seizures. AB - PURPOSE: Methylmalonic acidemias are inherited metabolic disorders characterized by methylmalonate (MMA) accumulation and neurologic dysfunction, including seizures. It is known that metabolic crises in affected patients are precipitated by infections. Although growing evidence supports that inflammation facilitates seizures, it is not known whether inflammatory mediators facilitate MMA-induced seizures. Therefore, in this study we investigate the involvement of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in MMA-induced seizures. METHODS: Adult male Wistar rats were implanted with electrodes over the parietal cortex for electroencephalography (EEG) recording and a cannula in the right lateral ventricle. Animals were injected with PGE(2) (100 ng/2 MUl, i.c.v.) or phosphate-buffered saline (PBS) (2 MUl, i.c.v.), 15 min before MMA (2.5 MUmol/2.5 MUl, i.c.v.) or NaCl (2.5 MUmol/2.5 MUl, i.c.v.). The anticonvulsant effect of celecoxib (0.2; 2 or 20 mg/kg, p.o., 60 min before MMA) on MMA-induced seizures, and whether PGE(2) (10 or 100 ng/2 MUl, i.c.v.) prevented the anticonvulsant effect of celecoxib (2 mg/kg, p.o.) were also investigated. KEY FINDINGS: PGE(2) decreased the latency to MMA-induced jerks and generalized seizures, and increased the amplitude of generalized seizure EEG recordings. The selective COX 2 inhibitor celecoxib at the dose 2 mg/kg, but not at the dose 20 mg/kg, completely prevented MMA-induced seizures. The protective effect of celecoxib (2 mg/kg) against MMA-induced seizures was prevented by PGE(2). SIGNIFICANCE: These results support a role for PGE(2) in the seizures elicited by MMA, which is in agreement with the view that infections may precipitate and exacerbate neurologic dysfunction in patients with MMA acidemic. PMID- 22091842 TI - Selection of Polychlorinated Biphenyls for use in Quantitative Structure-Activity Modelling. AB - Abstract By characterizing the 154 tetra- through heptachlorinated biphenyl (PCB) congeners with a multitude of physico-chemical descriptors, a model representing chemical similarities and differences is achieved. The multivariate characterization of the PCBs was based on 47 physico-chemical descriptor variables, which were summarised by using principal component analysis (PCA). By applying statistical design to the orthogonal scores from the PCA, a 2(4) factorial design was used to select a set of 16 congeners. In addition, four congeners were added to provide information about the interior region of the chemical domain of PCBs. This set of 20 structurally different congeners is suggested to be used in future quantitative structure-activity relationships (QSARs) for screening of the toxicological and biochemical effects of the PCBs. PMID- 22091839 TI - Recent progress in Bacillus subtilis sporulation. AB - The Gram-positive bacterium Bacillus subtilis can initiate the process of sporulation under conditions of nutrient limitation. Here, we review some of the last 5 years of work in this area, with a particular focus on the decision to initiate sporulation, DNA translocation, cell-cell communication, protein localization and spore morphogenesis. The progress we describe has implications not only just for the study of sporulation but also for other biological systems where homologs of sporulation-specific proteins are involved in vegetative growth. PMID- 22091843 TI - A General QSAR Model for Predicting the Toxicity of Organic Chemicals to Luminescent Bacteria (Microtox(r) test). AB - Abstract A large data set of Microtox(r) toxicity results was used to derive a general QSAR model. Chemicals were described by means of a modified autocorrelation method. The autocorrelation vectors were generated from atomic contributions encoding the hydrophobicity and molar refractivity of the molecules. A three-layer backpropagation neural network was used to design the model. The obtained results were compared with those obtained from a principal components regression analysis. PMID- 22091844 TI - Nonlinear Multivariate SAR of Lepidoptera Pheromones. AB - Abstract The combined use of the nonlinear mapping method with correspondence factor analysis allowed to derive interesting structure-chemoreception relationships in Lepidoptera. A chemotaxonomy of insects based on their responses to pheromones was also proposed. PMID- 22091845 TI - Modelling physico-chemical properties of halogenated benzenes: QSAR optimisation through variables selection. AB - Abstract This paper describes the development of multivariate QSAR models for halogenated benzenes. Four physico-chemical properties have been modelled: Boiling Point (BP), Melting Point (MP), Flash Point (FP) and Density (D). For the multivariate characterisation of this class of compounds 90 topological indices derived from the chemical formula were used. The models were calibrated on training sets selected by a D-optimal design and were optimised by a statistical procedure of selection of the most informative variables. The predictive capacity of the resulting models measured in terms of the parameter SDEP (Standard Deviation of the Errors of Predictions) were as follows; MP: +/- 21 +/-C (with MP ranging from -48 degrees to 181 degrees C); BP: +/-13 degrees C (75 degrees to 286 degrees C); D: +/-0.14 (1.02 to 2.52 g/cm(3)); FP: +/-17 degrees C (-12 to 126 degrees C). These data were confirmed "experimentally", i.e., on external validation sets of compounds, the experimental values of the standard deviation of prediction errors were in fact as follows; MP: +/-30 degrees C; BP: +/-16 degrees C D: +/-0.18 g/cm(3); FP: +/-16 degrees C. The developed models therefore provide a valuable tool for estimating physico-chemical properties relevant to environmental chemistry. PMID- 22091846 TI - Editorial board page for "SAR and QSAR in Environmental Research", Volume 4, Number 1. AB - Abstract This is a scanned image of the original Editorial Board page(s) for this issue. PMID- 22091847 TI - Separation of sunscreens in skincare creams using greener high-temperature liquid chromatography and subcritical water chromatography. AB - In this study, high-temperature liquid chromatographic (HTLC) and subcritical water chromatographic (SBWC) separations of sunscreens contained in skincare creams were achieved at temperatures ranging from 90 to 250 degrees C. The columns employed in this work include a ZirChrom-DiamondBond-C18, a XTerra MS C18 and a XBridge C18 column. The quantity of methanol consumed by the greener HTLC sunscreen methods developed in this project is significantly reduced although the HTLC separation at this stage is not as efficient as that achieved by traditional HPLC. SBWC separation of sunscreens was also achieved on the XTerra MS C18 and the XBridge C18 columns using pure water at 230-250 degrees C. Methanol was eliminated in the SBWC methods developed in this study. PMID- 22091848 TI - Investigation of the photoinduced magnetization of copper octacyanomolybdates nanoparticles by X-ray magnetic circular dichroism. AB - Through an extensive set of SQUID magnetic measurements, X-ray absorption spectroscopy, and X-ray magnetic circular dichroism, we have determined the nature of the metastable photomagnetic phase in the cyano-bridged 3D network Cs(2)Cu(7)[Mo(CN)(8)](4). The photomagnetic effect is induced by the photoconversion of Mo(IV) ions in low spin (LS) configuration (S = 0) into Mo(IV) ions in high spin (HS) configuration (S = 1). The magnetic and spectroscopic measurements fully support the LS to HS conversion, whereas the previously invoked charge transfer mechanism Mo(IV) + Cu(II) => Mo(V) + Cu(I) can be completely ruled out. PMID- 22091849 TI - The association of health insurance and disease impairment with reported asthma prevalence in U.S. children. AB - OBJECTIVE: To test the hypotheses that reported asthma prevalence is higher among insured than uninsured children and that insurance-based differences in asthma diagnosis, treatment, and health care utilization are associated with disease severity. DATA SOURCES: National Health and Nutrition Examination Survey, 2003 2008. STUDY DESIGN: We used multivariate logistic regression to examine the relationship between insurance and asthma symptom severity with asthma diagnosis, treatment, and acute care utilization. PRINCIPAL FINDINGS: In multivariate analysis, insured children had greater odds of reporting a current diagnosis of asthma than uninsured children (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.47-2.94). When interactions between insurance and asthma impairment were included, insurance was associated with greater odds of diagnosis among children with intermittent (OR = 4.08, 95% CI: 1.57-10.61), but not persistent, symptoms. Among children with intermittent symptoms, insurance was associated with inhaled corticosteroid use (OR = 4.51, 95% CI: 1.18-17.24) and asthma-related acute care utilization (OR = 5.21, 95% CI: 1.21-23.53); these associations were nonsignificant among children with persistent symptoms. CONCLUSION: Being insured increases only the likelihood that a child with intermittent, not persistent, asthma symptoms will receive an asthma diagnosis and control medication, and it may not reduce acute care utilization. Although universal insurance may increase detection and management of undiagnosed childhood asthma, theorized cost savings from reduced acute care utilization might not materialize. PMID- 22091850 TI - SPR Award, 2010. For distinguished contributions to psychophysiology: Judith M. Ford. PMID- 22091851 TI - Population estimates for Bangladesh: The use of a specific transitional population model. AB - Summary The development of population in Bangladesh was affected by a succession of man-made and natural calamities, such as the Bengal Famine of 1943, refugee movements following the partition of India and Pakistan in 1947, devastating floods and cyclones around 1970, and the military action during the war of liberation. Though there had been a tradition of census taking and vital registration in Bangladesh, as part of the Indian sub-continent, extending for over a century, vital registration was so deficient as to be almost valueless, and there were gross misstatements of age and under-enumeration in the censuses. In the census of 1941, on the other hand, political manoeuvring led to a substantial overcount of the population. In this paper, Bangladesh population trends are studied within the broader framework of the subcontinent, taking account of plausible differentials. A considerable element of uncertainty was introduced into growth trends as a result of variations in the completeness of census-taking and of unrecorded refugee and labour movements across open land borders. In this connection the substantial inflationary bias associated with techniques of population estimation using the dual record system is discussed. The application of stable population models is even less justified in Bangladesh with its history of declining mortality. A transitional age structure model was constructed on the basis of the information available on declining mortality and accelerating growth and the model was made even more specific by modifications which took care of the impact of recent calamities and of unrecorded migration. The population base of the census of 1961 was adjusted in accordance with this model. The local mortality age pattern was used in projecting the population by sex and age groups to the date at which the census was originally due to be taken in 1971, and to the date when it was actually taken in March 1974. The post-1970 calamities and their effect on mortality were ignored. The aggregate estimate of population of 72.9 million in March 1974 is slightly in excess of the census count (by about two per cent) reported provisionally as 71.3 million. The excess in our estimate could be accounted for by the losses due to cyclone and military action. PMID- 22091852 TI - Attitudes toward family size in some East European countries. AB - Summary The paper is a review of published materials on attitudes toward family size derived from nationwide family planning studies conducted in Czechoslovakia, Hungary, Poland and the USSR around 1970. Priority is given to the findings on expected family size, though other attitudinal variables such as the ideal number of children and/or the number planned at marriage are also discussed. The paper shows that the majority of women in all the countries surveyed tend to have a limited number of children. Although the trend is especially striking among better-educated and gainfully employed women, it is also spreading fast, particularly among the younger generations, through the whole urban and rural population. The average expected family size is generally close to, and for a sizeable group of women below, replacement level. The trend toward a small family size is only partially a reflection of real desires. Various factors, most of them apparently of an economic nature, prompt many women to have fewer children than they would wish. If the average expected fertility were equal to that considered as ideal or to that planned at marriage there would be no danger that births would fall below replacement level. In contrast to the situation in the countries as a whole, women in the Asian Republics of the USSR not only expect but also tend to regard as ideal a family with larger numbers of children. PMID- 22091853 TI - Parental survival data: Some results of the application of Ledermann's model life tables. AB - Summary Ledermann's one- and two-parameter model life tables are used in order to summarize and compare adult mortality estimates derived from parental survival data, and also to link parental survival with child survival data. The Ledermann models provide an alternative to the logit model used by Brass and Hill. Examination of life tables derived from actual child and adult mortality estimates reveals that although the two types of models yield similar overall levels of mortality, they show marked differences in the estimated patterns by sex and age. It has not been possible to disentangle completely how much of this divergence is due to the models themselves and how much to inadequacies in the data available. Finally, we question whether it is always wise to establish a full life table from child and adult mortality estimates when these are based on data which refer to different periods of exposure to the risk of dying, without allowance for possible distortions resulting from mortality change. PMID- 22091854 TI - Government perceptions of population growth. AB - Summary This paper seeks to evaluate the extent to which the world's population is represented by governments that judge population growth largely in terms of their countries' socio-economic capacity to absorb such growth. The initial data base consists of 125 countries, representing approximately 94 per cent of the world's population, classified according to whether their governments perceive their rates of population growth as deficient, satisfactory or excessive. Using various socio-economic development indices, a crude attempt is made to assess linkages between government perceptions and absorptive capacity. Results lead to insights into why some governments perceive their population situation at variance with the popular tide of opinion about desirability of reducing population growth everywhere. PMID- 22091855 TI - Demographic crisis: The impact of the Bangladesh civil war (1971) on births and deaths in a rural area of Bangladesh. AB - Summary In Matlab Bazaar Thana the Cholera Research Laboratory has registered the births, deaths and migrations in a population of approximately 125,000 since 1966. Although this rural area was not the scene of any significant armed encounters, striking changes in birth and death rates were registered during and after the conflict. Birth rates did not change during the relatively brief period of the civil war, but a small decline was registered for one year after the war. Fertility rates which had been declining slightly and irregularly in the pre-war baseline period may have increased slightly during the war and fell substantially in all age groups in the year following the war. The crude death rate, which rose by 37 per cent during the war, was a very sensitive reflection of the administrative and economic problems. Overall infant mortality rose by only 15 per cent over pre-war levels because all of the increase was observed in the post neo-natal component, which traditionally accounts for less than one-third of the total infant mortality in Bangladesh. Children and older adults accounted for the majority of excess deaths which were largely attributed to acute diarrhoeas and other gastro-intestinal causes. The death rate at ages 1-4 rose by 43 per cent and at ages 5-9 soared to 208 per cent above pre-war baseline rates. All increases in age-specific mortality rates fell to baseline levels during the year following the war, except the 5-9-year age group, in which rates continued to be high largely because of deaths due to dysentery. PMID- 22091856 TI - Pro-natalist population policies in Czechoslovakia. AB - Summary Given the high rate of women's employment and the lack of labour reserves, other than the natural replacement of the population, pro-natalist population policy in Czechoslovakia should be seen as a response to an anticipated shortage of labour. The rapid post-war decline in the birth rate has been caused by the greatly increased opportunity structure for women in education and employment, and by other policies favouring lower natality - rapid urbanization, inadequate provision of housing, insufficient investment in consumers' goods and services, low wages and relatively free availability of abortion. To reverse this undesirable population trend, the Czechoslovak government has adopted a more restrictive attitude towards abortion, lengthened paid maternity leave, increased family allowances and single grants given at childbirth and introduced the so-called maternity allowance, which is a direct monthly payment given by the state to mothers who wish to stay at home to raise a second or subsequent child, until the child is two years old. The time so spent counts towards the mother's retirement pension and other kinds of seniority, and her job is held open for her. These measures have contributed to the recent increase in the Czechoslovak birth rate, but more time is needed for the assessment of the long-term effectiveness of these measures. PMID- 22091857 TI - Cohort nuptiality in England and Wales. AB - Summary A computerized nuptiality system, called GENMAR, has been developed to investigate trends in cohort nuptiality in England and Wales. This system has five main programmes dealing with first marriage, the effects of changes in mortality on nuptiality measures, divorce, re-marriage, and marital status distribution. This paper summarizes the results of the application of the first programme to England and Wales data on first marriages of persons who were born in every single year since 1900. GENMAR-1 generated for each of these cohorts a 'complete' gross nuptiality table. The analysis shows that there have been substantial increases in the intensity of first marriage at young ages, a downward shift in the modal age at marriage, and a significant rise in the proportion ever married among women. The cohort nuptiality tables also show that the change in the nuptiality of women was due to changes in both the tempo and level of nuptiality, whereas the change for men was mainly the effect of shifts in the temporal pattern of nuptiality. There are, however, signs of a slow down of marriage among the cohorts born since the early 1950's. PMID- 22091858 TI - Matching experimentation in a dual record system for births and deaths in Morocco. AB - Summary In an effort to improve the quality and completeness of birth and death reporting in Morocco, a sample of 84,000 persons was established, for whom birth and death data were collected by two methods. Each household was contacted once a month by interviewers in a registration method; independently, each household was interviewed once every six months by a survey team. Interviewing continued from April 1972 to July 1973. Results of these two methods were then compared through matching the vital events recorded by the two sources. First a 'true match status' was established by teams of 'experts', supplemented by field verification of uncertain cases. Of the 15 variables on the vital event reporting forms, eight were studied to establish the optimal tolerance limits for deciding whether any two completed recording forms (one from each method) were recording a single birth (or death) or two different ones. Next, those characteristics were selected which introduced the fewest matching errors; for births, this was the dwelling unit number, the name of the mother, and the name of the baby; for deaths, the dwelling unit number, the name of the person, and the name of the head of household. Aside from its manifest function, the matching operation also improved the fieldwork and helped to clean the data. PMID- 22091859 TI - Methods of adjusting the stable estimates of fertility for the effects of mortality decline. AB - Summary The paper shows how stable population methods, based on the age structure and the rate of increase, may be used to estimate the demographic measures of a quasi-stable population. After a discussion of known methods for adjusting the stable estimates to allow for the effects of mortality decline two new methods are presented, the application of which requires less information. The first method does not need any supplementary information, and the second method requires an estimate of the difference between the last two five-year intercensal rates of increase, i.e. five times the annual change of the rate of increase during the last ten years. For these new methods we do not need to know the onset year of mortality decline as in the Coale-Demeny method, or a long series of rates of increase as in Zachariah's method. PMID- 22091862 TI - Common data elements for research on traumatic brain injury: pediatric considerations. AB - Traumatic brain injury (TBI) is a significant global health problem, with a notably high incidence in children and adolescents. Despite the prevalence of TBI and the disabilities that often follow, research on which to base effective treatment is limited by several challenges, including but not limited to the complexity and heterogeneity of TBI. Even when rigorous methods are employed, the utility of the research may be limited by difficulties in comparing findings across studies resulting from the use of different measures to assess similar TBI study variables. Standardization of definitions and data elements is an important step toward accelerating the process of data sharing that will ultimately lead to a stronger evidence base for treatment advances. To address this need, recommendations for common data elements (CDEs) for research on TBI were developed through a 2009 national initiative. To ensure that the TBI CDE recommendations are relevant to pediatric populations, the National Institute on Disability and Rehabilitation Research (NIDRR) and the National Institute of Neurological Disorders and Stroke (NINDS) called for a review of the original recommendations. Following the process used for the original initiative, multidisciplinary work groups composed of pediatric TBI experts were formed (Demographics and Clinical Assessment; Biomarkers; Neuroimaging; and Outcomes Assessment). Recommendations for modifications and additions to the original CDEs were developed by the work groups, vetted at a 2010 workshop and further refined in preparation for publication. The pediatric considerations for TBI CDEs are described in a series of articles in this journal. This article describes the efforts leading to this pediatric CDE initiative and the CDE review and development process. It concludes with general recommendations for future iterations of the CDE initiative. PMID- 22091863 TI - Lost in transition. PMID- 22091864 TI - Antimicrobial applications of electroactive PVK-SWNT nanocomposites. AB - The antibacterial properties of a nanocomposite containing an electroactive polymer, polyvinyl-N-carbazole (PVK) (97 wt %), and single-walled carbon nanotubes (SWNT) (3 wt %) was investigated as suspensions in water and as thin film coatings. The toxic effects of four different PVK-SWNT (97:3 wt %) nanocomposite concentrations (1, 0.5, 0.05, and 0.01 mg/mL) containing 0.03, 0.015, 0.0015, and 0.0003 mg/mL of SWNT, respectively, were determined for planktonic cells and biofilms of Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis). The results showed that the nanocomposite PVK-SWNT had antibacterial activity on planktonic cells and biofilms at all concentration levels. Higher bacterial inactivation (94% for E. coli and 90% for B. subtilis) were achieved in planktonic cells at a PVK-SWNT concentration of 1 mg/mL. Atomic force microscopy (AFM) imaging showed significant reduction of biofilm growth on PVK-SWNT coated surfaces. This study established for the first time that the improved dispersion of SWNTs in aqueous solutions in the presence of PVK enhances the antimicrobial effects of SWNTs at very low concentrations. Furthermore, PVK SWNT can be used as an effective thin film coating material to resist biofilm formation. PMID- 22091865 TI - The neuroregenerative mechanism mediated by the Hsp90-binding immunophilin FKBP52 resembles the early steps of neuronal differentiation. AB - BACKGROUND AND PURPOSE The immunosuppressive macrolide FK506 (tacrolimus) shows neuroregenerative action by a mechanism that appears to involve the Hsp90-binding immunophilin FKBP52. This study analyses some aspects of the early steps of neuronal differentiation and neuroregeneration. EXPERIMENTAL APPROACH Undifferentiated murine neuroblastoma cells and hippocampal neurones isolated from embryonic day-17 rat embryos were induced to differentiate with FK506. Subcellular relocalization of FKBP52, Hsp90 and its co-chaperone p23 was analysed by indirect immunofluorescence confocal microscopy and by Western blots of axonal fractions isolated from cells grown on a porous transwell cell culture chamber. Neuroregeneration was evaluated using a scratch-wound assay. KEY RESULTS In undifferentiated cells, FKBP52, Hsp90 and p23 are located in the cell nucleus, forming an annular structure that disassembles when the differentiation process is triggered by FK506. This was observed in the N2a cell line and in hippocampal neurones. More importantly, the annular structure of chaperones is reassembled after damaging the neurones, whereas FK506 prompts their rapid regeneration, a process linked to the subcellular redistribution of the heterocomplex. CONCLUSIONS AND IMPLICATIONS There is a direct relationship between the disassembly of the chaperone complex and the progression of neuronal differentiation upon stimulation with the immunophilin ligand FK506. Both neuronal differentiation and neuroregeneration appear to be mechanistically linked, so the elucidation of one mechanism may lead to unravel the properties of the other. This study also implies that the discovery of FK506 derivatives, devoid of immunosuppressive action, would be therapeutically significant for neurotrophic use. PMID- 22091866 TI - Nonspecific interaction between DNA and protein allows for cooperativity: a case study with mycobacterium DNA binding protein. AB - Different DNA-binding proteins have different interaction modes with DNA. Sequence-specific DNA-protein interaction has been mostly associated with regulatory processes inside a cell, and as such extensive studies have been made. Adequate data is also available on nonspecific DNA-protein interaction, as an intermediate to protein's search for its cognate partner. Multidomain nonspecific DNA-protein interaction involving physical sequestering of DNA has often been implicated to regulate gene expression indirectly. However, data available on this type of interaction is limited. One such interaction is the binding of DNA with mycobacterium DNA binding proteins. We have used the Langmuir-Blodgett technique to evaluate for the first time the kinetics and thermodynamics of Mycobacterium smegmatis Dps1 binding to DNA. By immobilizing one of the interacting partners, we have shown that, when a kinetic bottleneck is applied, the binding mechanism showed cooperative binding (n = 2.72) at lower temperatures, but the degree of cooperativity gradually reduces (n = 1.38) as the temperature was increased. We have also compared the kinetics and thermodynamics of sequence-specific and nonspecific DNA-protein interactions under the same set of conditions. PMID- 22091867 TI - A tutorial on hierarchically structured constructs. AB - Many psychological constructs are conceived to be hierarchically structured and thus to operate at various levels of generality. Alternative confirmatory factor analytic (CFA) models can be used to study various aspects of this proposition: (a) The one-factor model focuses on the top of the hierarchy and contains only a general construct, (b) the first-order factor model focuses on the intermediate level of the hierarchy and contains only specific constructs, and both (c) the higher order factor model and (d) the nested-factor model consider the hierarchy in its entirety and contain both general and specific constructs (e.g., bifactor model). This tutorial considers these CFA models in depth, addressing their psychometric properties, interpretation of general and specific constructs, and implications for model-based score reliabilities. The authors illustrate their arguments with normative data obtained for the Wechsler Adult Intelligence Scale and conclude with recommendations on which CFA model is most appropriate for which research and diagnostic purposes. PMID- 22091868 TI - Cardiovascular and cortisol reactions to acute psychological stress and cognitive ability in the Dutch Famine Birth Cohort Study. AB - Given evidence linking blunted cardiovascular and cortisol reactions to acute stress and a range of adverse behavioral outcomes, the present study examined the associations between cardiovascular and cortisol reactivity and cognitive ability measured independently of the stress task exposure. Cognitive ability was assessed using the Alice Heim-4 test of general intelligence and two memory tasks in 724 men and women who were part of the Dutch Famine Birth Cohort Study. Blood pressure and heart rate, as well as cortisol reactivity, were measured to a battery of three standard acute stress tasks. Poorer cognitive ability was associated with lower cardiovascular reactions to stress and lower cortisol area under the curve. Our results are consistent with recent findings implicating low physiological stress reactivity in a range of adverse behavioral and health outcomes. PMID- 22091869 TI - Binding of ibuprofen, ketorolac, and diclofenac to COX-1 and COX-2 studied by saturation transfer difference NMR. AB - Saturation transfer difference NMR (STD-NMR) spectroscopy has emerged as a powerful screening tool and a straightforward way to study the binding epitopes of active compounds in early stage lead discovery in pharmaceutical research. Here we report the application of STD-NMR to characterize the binding of the anti inflammatory drugs ibuprofen, diclofenac, and ketorolac to COX-1 and COX-2. Using well-studied COX inhibitors and by comparing STD signals with crystallographic structures, we show that there is a relation between the orientations of ibuprofen and diclofenac in the COX-2 active site and the relative STD responses detected in the NMR experiments. On the basis of this analysis, we propose that ketorolac should bind to the COX-2 active site in an orientation similar to that of diclofenac. We also show that the combination of STD-NMR with competition experiments constitutes a valuable tool to address the recently proposed behavior of COX-2 as functional heterodimers and complements enzyme activity studies in the effort to rationalize COX inhibition mechanisms. PMID- 22091870 TI - Electronic-state switching strategy in the photochemical synthesis of indanones from o-methyl phenacyl epoxides. AB - An electronic excited-state switching strategy has been utilized to control the selectivity of a key photochemical step in the total synthesis of indanorine. The excited-state character of 4,5-dimethoxy-2-methylphenacyl epoxide was changed from an unfavorable (3)pi,pi* state to a productive (3)n,pi* state by a temporary structural modification, resulting in a relatively efficient and high-yielding formation of an indanone derivative. The corresponding structural modification was selected on the basis of quantum chemical calculations prior to the synthesis. PMID- 22091872 TI - Quantification of humeroulnar incongruity in labrador retrievers with and without medial coronoid disease. AB - OBJECTIVE: To quantify humeroulnar incongruity on elbow radiographs in Labrador Retrievers with or without medial coronoid disease (MCD). STUDY DESIGN: Retrospective study of 92 elbows. SAMPLE POPULATION: Radiographic projections of elbow joints from Labrador Retrievers with MCD (n = 42 elbows; 26 dogs) and without MCD (n = 50 elbows; 25 dogs). PROCEDURE: The congruity of the humeroulnar joint was measured using an index of subluxation (SI) for each elbow. SI was defined as the distance between the centers of 2 circles drawn along the margins of the incisura trochlearis and the trochlea of humerus on mediolateral digital radiographic projections, normalized by the radius of the circle circumscribing the humeral trochlea. SI was compared between right and left elbows with and without pathology using a Wilcoxon test for paired data, and between normal and abnormal groups with a Wilcoxon test for unpaired data. Mismatch between ulnar curvature and curvature of humeral trochlea and radioulnar incongruency were also noted (Wilcoxon test). The intraobserver repeatability, correlation between SI and radioulnar incongruency, and between SI and mismatch elbow curvature were estimated with a Pearson's correlation coefficient. RESULTS: Intraobserver repeatability of SI measurement was high (r = 0.97). Mean +/- SD humeroulnar incongruity (SI) was greater in elbows with MCD (18.5 +/- 6.6) than in the normal elbows (1.7 +/- 2.0, P < 0.001). The difference between the diameters of the curvatures of the ulnar and humeral trochlea was greater in elbows with MCD (12.5 +/- 4.4) than in the normal group (10.7 +/- 4.1, P < 0.05). A moderate correlation was found between the degree of humeroulnar incongruity and a radioulnar step (r = 0.63); however, no correlation was identified between SI and the difference between the diameters of the curvatures of the ulnar and humeral trochleae (r = 0.14). CONCLUSION: We propose a radiographic index to measure humeroulnar incongruity on mediolateral digital radiographic projections. This index (SI) supports the presence of humeroulnar incongruity in Labrador Retrievers with MCD. Further evaluation of its reproducibility and clinical importance are warranted. Although there is a moderate correlation between humeroulnar incongruity and radioulnar incongruency, causation has not been established. PMID- 22091871 TI - The effects of safety net hospital closures and conversions on patient travel distance to hospital services. AB - OBJECTIVE: To examine the effects of safety net hospital (SNH) closure and for profit conversion on uninsured, Medicaid, and racial/ethnic minorities. DATA SOURCES/EXTRACTION METHODS: Hospital discharge data for selected states merged with other sources. STUDY DESIGN: We examined travel distance for patients treated in urban hospitals for five diagnosis categories: ambulatory care sensitive conditions, referral sensitive conditions, marker conditions, births, and mental health and substance abuse. We assess how travel was affected for patients after SNH events. Our multivariate models controlled for patient, hospital, health system, and neighborhood characteristics. PRINCIPAL FINDINGS: Our results suggested that certain groups of uninsured and Medicaid patients experienced greater disruption in patterns of care, especially Hispanic uninsured and Medicaid women hospitalized for births. In addition, relative to privately insured individuals in SNH event communities, greater travel for mental health and substance abuse care was present for the uninsured. CONCLUSIONS: Closure or for-profit conversions of SNHs appear to have detrimental access effects on particular subgroups of disadvantaged populations, although our results are somewhat inconclusive due to potential power issues. Policy makers may need to pay special attention to these patient subgroups and also to easing transportation barriers when dealing with disruptions resulting from reductions in SNH resources. PMID- 22091873 TI - The influence of oral VPA on the required dose of propofol for sedation during dental treatment in patients with mental retardation: a prospective observer blinded cohort study. AB - In sedation of dental patients with moderate or severe mental retardation, it is difficult to identify the optimum sedation level and to maintain it appropriately. Moreover, many patients have concomitant epilepsy and are medicated with oral antiepileptic drugs (AEDs), which influence the drug metabolizing enzymes. In particular, valproate (VPA) has been demonstrated to inhibit propofol metabolism in vitro. Therefore, the objective of the present study was to investigate the clinical influence of oral VPA on the required dose of propofol for sedation, with use of a prospective cohort study design. We studied 45 patients with moderate or severe mental retardation who underwent dental treatment under sedation. Propofol was infused, and sedation was maintained at the same level in all patients using a bispectral index (BIS) monitor. After the completion of treatment for the scheduled patients, patients were divided into those with oral VPA treatment (VPA group: 20 patients) and without any oral antiepileptic treatment (control group: 25 patients). The propofol dose required for sedation and times to the recovery of the eyelash reflex and spontaneous eye opening were evaluated. The median required propofol doses in the VPA and control groups were 4.15 (range 1.97-5.88) and 5.67 (2.92 7.17) mg/kg/h, respectively. We observed a statistically significant difference between the two patient groups with respect to median VPA dose (p < 0.01). However, no statistically significant differences were noted in the time until eyelash reflex recovery or spontaneous eye opening between the two groups. The results suggest that oral VPA reduces the dose of propofol required for sedation during dental treatment in patients with moderate or severe mental retardation. PMID- 22091874 TI - Health behaviors as predictors for declines in higher-level functional capacity in older adults: the Ohasama study. AB - OBJECTIVES: To determine the characteristics of health behaviors related to higher-level functional decline in older community-dwelling adults. DESIGN: Prospective. SETTING: Ohasama Town, Japan. PARTICIPANTS: One thousand fifty residents (mean age: 67.5) free of functional decline at baseline. MEASUREMENTS: Health behaviors including smoking status, alcohol consumption, frequency of exercise, sleep duration, dietary habits (supplement use, breakfast, late-night snacking, eating regularly, and eating out), and self-rated health were obtained from a self-administered questionnaire at baseline. Higher-level functional decline was examined using the subscales of the Tokyo Metropolitan Institute of Gerontology Index of Competence. RESULTS: During the 7-year follow-up, 27.5% of eligible participants reported decline in higher-level functional capacity. After adjustment for putative confounding factors, health behaviors that were significant predictors for declines in higher-level functional capacity at the 7 year follow-up were current smoking (odds ratio (OR) = 1.58, 95% confidence interval (CI) = 1.06-2.36), sleep duration of 9 hours or longer (OR = 2.15, 95% CI = 1.49-3.11), and poor self-rated health (OR = 1.93, 95% CI = 1.40-2.67). CONCLUSION: Several modifiable health behaviors contribute to higher-level functional decline. PMID- 22091875 TI - The essential role of psychosocial risk and protective factors in pediatric traumatic brain injury research. AB - This article builds upon Traumatic Brain Injury Common Data Elements (TBI CDE) version 1.0 and the pediatric CDE Initiative by emphasizing the essential role of psychosocial risk and protective factors in pediatric TBI research. The goals are to provide a compelling rationale for including psychosocial risk and protective factors in addition to socioeconomic status (SES), age, and sex in the study design and analyses of pediatric TBI research and to describe recommendations for core common data elements in this domain. Risk and protective factor research is based on the ecological theory of child development in which children develop through a series of interactions with their immediate and more distant environments. Home, school, religious, and social influences are conceptualized as risk and/or protective factors. Child development and TBI researchers have interpreted risk and protective variables as main effects or as interactions and have used cumulative risk indices and moderation models to describe the relationship among these variables and outcomes that have to do with development and with recovery from TBI. It is likely that the number, type, and interaction among risk and protective factors each contribute unique variance to study outcomes. Longitudinal designs in TBI research will be essential to understanding the reciprocal relationships between risk/protective factors and the recovery/outcome made by the child. The search for effective interventions to hasten TBI recovery mandates the need to target modifiable risks and to promote protective factors in the child's environment. PMID- 22091876 TI - Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats. AB - Gentamicin (GM) is a widely used antibiotic against serious, life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of selenium (Se) in GM-induced nephrotoxicity in rats. Experiments were done on 32 adult Wistar rats divided into four groups of 8 animals each. The GM group received gentamicin (100 mg/kg), whereas the GM+Se group received the same dose of GM and selenium (1 mg/kg) by intraperitoneal (i.p.) injections on a daily basis. Animals in the Se group, serving as a positive control, received only selenium (1 mg/kg) and the control group received saline (1 mL/day), both given i.p. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of selenium coadministration with GM. GM was observed to cause a severe nephrotoxicity, which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous selenium administration protected kidney tissue against oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by selenium pretreatment. The results from our study indicate that selenium supplementation attenuates oxidative-stress-associated renal injury by reducing oxygen free radicals and lipid peroxidation in GM-treated rats. PMID- 22091877 TI - The relationship between measures of impulsivity and alcohol misuse: an integrative structural equation modeling approach. AB - BACKGROUND: Higher levels of impulsivity have been implicated in the development of alcohol use disorders. Recent findings suggest that impulsivity is not a unitary construct, highlighted by the diverse ways in which the various measures of impulsivity relate to alcohol use outcomes. This study simultaneously tested the following dimensions of impulsivity as determinants of alcohol use and alcohol problems: risky decision making, self-reported risk-attitudes, response inhibition, and impulsive decision making. METHODS: Participants were a community sample of nontreatment seeking problem drinkers (n = 158). Structural equation modeling (SEM) analyses employed behavioral measures of impulsive decision making (delay discounting task [DDT]), response inhibition (stop signal task [SST]), and risky decision making (Balloon Analogue Risk Task [BART]), and a self-report measure of risk-attitudes (domain-specific risk-attitude scale [DOSPERT]), as predictors of alcohol use and of alcohol-related problems in this sample. RESULTS: The model fits well, accounting for 38% of the variance in alcohol problems, and identified 2 impulsivity dimensions that significantly loaded onto alcohol outcomes: (i) impulsive decision making, indexed by the DDT; and (ii) risky decision making, measured by the BART. CONCLUSIONS: The impulsive decision making dimension of impulsivity, indexed by the DDT, was the strongest predictor of alcohol use and alcohol pathology in this sample of problem drinkers. Unexpectedly, a negative relationship was found between risky decision making and alcohol problems. The results highlight the importance of considering the distinct facets of impulsivity to elucidate their individual and combined effects on alcohol use initiation, escalation, and dependence. PMID- 22091879 TI - Cognitive reappraisal and secondary control coping: associations with working memory, positive and negative affect, and symptoms of anxiety/depression. AB - The current study examined the relations of measures of cognitive reappraisal and secondary control coping with working memory abilities, positive and negative affect, and symptoms of anxiety and depression in young adults (N=124). Results indicate significant relations between working memory abilities and reports of secondary control coping and between reports of secondary control coping and cognitive reappraisal. Associations were also found between measures of secondary control coping and cognitive reappraisal and positive and negative affect and symptoms of depression and anxiety. Further, the findings suggest that reports of cognitive reappraisal may be more strongly predictive of positive affect whereas secondary control coping may be more strongly predictive of negative affect and symptoms of depression and anxiety. Overall, the results suggest that current measures of secondary control coping and cognitive reappraisal capture related but distinct constructs and suggest that the assessment of working memory may be more strongly related to secondary control coping in predicting individual differences in distress. PMID- 22091880 TI - The status of unmarried Hong Kong women and the social factors contributing to their delayed marriage. AB - Summary The Dixon model, which assesses the factors responsible for a rise in marriage age, has been applied to a number of Hong Kong women, aged from 20 to 24 in 1973, who were interviewed in depth. Four of them have delayed marriage due to the unavailability of mates, in particular the new marriage style and difficulty of locating a companionable mate. For 21 marriage was not economically feasible. Three anticipated they would lose too many opportunities by early marriage which was consequently undesirable at that time; only one sought to gain opportunities by a young marriage. All three factors work in concert to some extent. The age structure contributes to women's participation in the labour force and they could meet neither their obligations to their families nor to themselves by marrying early. Delayed marriage enhances women's status, and is an attractive policy for the developing world. PMID- 22091878 TI - Theta lingua franca: a common mid-frontal substrate for action monitoring processes. AB - We present evidence that a multitude of mid-frontal event-related potential (ERP) components partially reflect a common theta band oscillatory process. Specifically, mid-frontal ERP components in the N2 time range and error-related negativity time range are parsimoniously characterized as reflections of theta band activities. Forty participants completed three different tasks with varying stimulus-response demands. Permutation tests were used to identify the dominant time-frequency responses of stimulus- and response-locked conditions as well as the enhanced responses to novelty, conflict, punishment, and error. A dominant theta band feature was found in all conditions, and both ERP component amplitudes and theta power measures were similarly modulated by novelty, conflict, punishment, and error. The findings support the hypothesis that generic and reactive medial prefrontal cortex processes are parsimoniously reflected by theta band activities. PMID- 22091881 TI - Fertility and work-force participation: The experience of Melbourne Wives. AB - Summary Current and retrospective data on the fertility control, work-force participation intentions and practice of Melbourne wives are combined in an examination of the causal link between work-force participation and reduced family size. Stress is laid on the analysis of the interaction between work-force participation and fertility over time, taking into account the proportion of married life spent in the work-force, rather than relying exclusively on a measure of current participation, the only option available in the analysis of census-type data. The wide range of information available makes it possible to study the effects of work-force participation on wives of unimpaired fertility, as well as the different consequences of planned and unplanned participation, and of working in a variety of occupations and for a number of distinct reasons. Examination of the future fertility intentions and current contraceptive practice of the younger wives shows that working wives are not, in these respects, markedly different from their house-wife peers. Overall, the balance of the evidence indicates that in the majority of cases fertility influences work-force participation rather than the converse. PMID- 22091882 TI - Economic development and fertility: A methodological re-evaluation. AB - Summary Several studies in recent years have investigated the relationship between economic development and fertility, using the methods of multiple and partial correlation. Results from these studies have been interpreted to show that economic development, while directly tending to increase fertility, also gives rise to factors which inhibit it, resulting in an eventual decrease in fertility with increasing development. The present study re-examines the methodology and empirical results upon which this explanation is based and finds little statistical or empirical support for such a model. Subsequent statistical re-examination of the data from one of these studies reveals that the major independent variables in the model are largely redundant, and that the model is untenable in that it seeks to establish patterns of interrelation between what appear to be redundant constructs. The isolation of additional statistically independent variables is suggested to improve the explanation of variance in fertility in terms of its social and economic correlates. PMID- 22091883 TI - Differential fertility in peasant communities: A study of Six Iranian Villages. AB - Summary This paper attempts to study the relation between socio-economic status and fertility in a sample of six villages in Iran. An index of socio-economic status was constructed. The data reveal positive association between socio economic status and fertility behaviour of rural couples. When duration of marriage, age of woman at marriage and contraceptive use were introduced into the socio-economic status-fertility relationships, they failed to alter the original findings. Because socio-economic status is related to a number of variables which directly or indirectly influence fertility, additional variables such as miscarriage, stillbirth and lactation must be incorporated into rural surveys on fertility differentials. PMID- 22091884 TI - A simulation of the impact of changes in age at marriage before and during the advent of industrialization in England. AB - Summary The quantitative significance of changes in age at marriage on family size is assessed by applying a simple simulation model of family reproduction, using data broadly related to England in the period 1700-1850. Within this context, the impacts of parity-specific infant mortality, and an association between age at marriage and potential fertility are considered. The evidence concerning variations in marriage and mortality distributions over the period in question is examined and linked to the simulation results to produce some tentative conclusions relating to the impact of changes in the distribution of age at marriage on the birth rate and rate of population growth and to an assessment of such changes as an homeostatic adjustment mech-anism. In particular, it is argued that age at marriage played no more than a secondary role in the English demographic revolution. PMID- 22091885 TI - Fertility and desired fertility: Longitudinal evidence from Thailand. AB - Summary The validity and usefulness of 'desired additional children' and 'ideal family size' as predictors of fertility are analysed in this paper on the basis of longitudinal survey data from Thailand. First, the extent of measurement error in these variables is considered, and it is concluded that the error variance and the true variance are of similar orders of magnitude. Secondly, the changes in attitudes subsequent to births and deaths of children are investigated. It is found that the number of additional children desired is decreased by births and increased by deaths, but less than would be expected if 'desired additional children' represented an unchanging target family size. 'Ideal family size' is almost unaffected by births and deaths. Thirdly, the contribution of attitudinal variables to behavioural models is examined. It is found that desired fertility is explained no better than fertility in a standard economic model. A birth function separating desired children from identifiable physiological factors as explanatory variables indicated that the former was just significant. A model of contraceptive acceptance also found desired fertility to be a significant determinant. Thus, desired fertility can be successfully integrated into behavioural models. But on the whole, its explanatory power was weak, and it was concluded that the independent use of this variable does not significantly improve on models which relate fertility to socio-economic variables directly. PMID- 22091886 TI - Age at marriage and timing of the first birth. AB - Summary An attempt has been made to measure the effect of age at marriage of brides on the timing of the first birth. In Australian vital statistics, first nuptial confinements have been tabulated by age of mothers and by single years of marriage duration in single months for the first two years and by single years for all other durations since 1916. A simple technique has been used to link such data with marriage cohorts. The study briefly reviews the prevailing patterns of the timing of first births by mothers' age at marriage and changes in this pattern since the marriages of the 1925/9 period. The analysis shows that after a period of relative stability of family formation patterns in the 1950s and early 1960s, women married in the late 1960s started postponing the first birth beyond the first two years of marriage. It is suggested that a fraction of the decline in total births recorded in Australia since 1972 can be attributed to the postponement of first nuptial confinements by women married in the late 1960s and early 1970s. PMID- 22091887 TI - Regional-sub-cultural explanations of black fertility in the United States. AB - Summary This paper re-examines the relevance of the hypothesis concerning the Southern sub-culture and black fertility in the United States. According to zero order correlation analysis, Southern-born blacks show higher fertility than those born in other regions. But a dummy-variable regression technique applied to the data from the 1970 public-use sample indicates that the Southern origin - independent of other factors-is not different from other regions. Southern birth has the effect of increasing black fertility, but much less so than birth in the North Central region. Southern blacks show higher fertility because of their lower socio-economic background. It is concluded that geographical regions in the United States have little or no cultural meaning in explaining reproductive behaviour. PMID- 22091890 TI - Errata. PMID- 22091891 TI - Computational prediction of 1H and 13C chemical shifts: a useful tool for natural product, mechanistic, and synthetic organic chemistry. PMID- 22091892 TI - Staphylococcus aureus and its food poisoning toxins: characterization and outbreak investigation. AB - Staphylococcal food poisoning (SFP) is one of the most common food-borne diseases and results from the ingestion of staphylococcal enterotoxins (SEs) preformed in food by enterotoxigenic strains of Staphylococcus aureus. To date, more than 20 SEs have been described: SEA to SElV. All of them have superantigenic activity whereas half of them have been proved to be emetic, representing a potential hazard for consumers. This review, divided into four parts, will focus on the following: (1) the worldwide story of SFP outbreaks, (2) the characteristics and behaviour of S. aureus in food environment, (3) the toxinogenic conditions and characteristics of SEs, and (4) SFP outbreaks including symptomatology, occurrence in the European Union and currently available methods used to characterize staphylococcal outbreaks. PMID- 22091893 TI - Comparative floc-bed sediment trace element partitioning across variably contaminated aquatic ecosystems. AB - Significantly higher concentrations of Ag, As, Cu, Ni and Co are found in floc compared to bed sediments across six variably impacted aquatic ecosystems. In contrast to the observed element and site-specific bed sediment trace element (TE) partitioning patterns, floc TE sequestration is consistently dominated by amorphous oxyhydroxides (FeOOH), which account for 30-79% of floc total TE concentrations, irrespective of system physico-chemistry or elements involved. FeOOH consistently occur in significantly higher concentrations in floc than within bed sediments. Further, comparative concentration factors indicate significantly higher TE reactivity of floc-FeOOH relative to sediment-FeOOH in all systems investigated, indicating that both the greater abundance and higher reactivity of floc-FeOOH contribute to enhanced floc TE uptake. Results indicate that floc-organics (live cells and exopolymeric substances, EPS) directly predict floc-FeOOH concentrations, suggesting an organic structural role in the collection/templating of FeOOH. This, in turn, facilitates the sequestration of TEs associated with floc-FeOOH formation, imparting the conserved FeOOH "signature" on floc TE geochemistry across sites. Results demonstrate that the organic rich nature of floc exerts an important control over TE geochemistry in aquatic environments, ultimately creating a distinct solid with differing controls over TE behavior than bed sediments in close proximity (<0.5 m). PMID- 22091894 TI - Chiral transformation: from single nanowire to double helix. AB - We report a new type of water-soluble ultrathin Au-Ag alloy nanowire (NW), which exhibits unprecedented behavior in a colloidal solution. Upon growth of a thin metal (Pd, Pt, or Au) layer, the NW winds around itself to give a metallic double helix. We propose that the winding originates from the chirality within the as synthesized Au-Ag NWs, which were induced to untwist upon metal deposition. PMID- 22091895 TI - Expanding the phenotype associated with FOXG1 mutations and in vivo FoxG1 chromatin-binding dynamics. AB - Mutations in the Forkhead box G1 (FOXG1) gene, a brain specific transcriptional factor, are responsible for the congenital variant of Rett syndrome. Until now FOXG1 point mutations have been reported in 12 Rett patients. Recently seven additional patients have been reported with a quite homogeneous severe phenotype designated as the FOXG1 syndrome. Here we describe two unrelated patients with a de novo FOXG1 point mutation, p.Gln46X and p.Tyr400X, respectively, having a milder phenotype and sharing a distinctive facial appearance. Although FoxG1 action depends critically on its binding to chromatin, very little is known about the dynamics of this process. Using fluorescence recovery after photobleaching, we showed that most of the GFP-FoxG1 fusion protein associates reversibly to chromatin whereas the remaining fraction is bound irreversibly. Furthermore, we showed that the two pathologic derivatives of FoxG1 described in this paper present a dramatic alteration in chromatin affinity and irreversibly bound fraction in comparison with Ser323fsX325 mutant (associated with a severe phenotype) and wild type Foxg1 protein. Our observations suggest that alterations in the kinetics of FoxG1 binding to chromatin might contribute to the pathological effects of FOXG1 mutations. PMID- 22091896 TI - Investigation of model membrane disruption mechanism by melittin using pulse electron paramagnetic resonance spectroscopy and cryogenic transmission electron microscopy. AB - Studies of membrane peptide interactions at the molecular level are important for understanding essential processes such as membrane disruption or fusion by membrane active peptides. In a previous study, we combined several electron paramagnetic resonance (EPR) techniques, particularly continuous wave (CW) EPR, electron spin echo envelope modulation (ESEEM), and double electron-electron resonance (DEER) with Monte Carlo (MC) simulations to probe the conformation, insertion depth, and orientation with respect to the membrane of the membrane active peptide melittin. Here, we combined these EPR techniques with cryogenic transmission electron microscopy (cryo-TEM) to examine the effect of the peptide/phospholipid (P/PL) molar ratio, in the range of 1:400 to 1:25, on the membrane shape, lipids packing, and peptide orientation and penetration. Large unilamellar vesicles (LUVs) of DPPC/PG (7:3 dipalmitoylphosphatidylcholine/egg phosphatidylglycerol) were used as model membranes. Spin-labeled peptides were used to probe the peptide behavior whereas spin-labeled phspholipids were used to examine the membrane properties. The cryo-TEM results showed that melittin causes vesicle rupture and fusion into new vesicles with ill-defined structures. This new state was investigated by the EPR methods. In terms of the peptide, CW EPR showed decreased mobility, and ESEEM revealed increased insertion depth as the P/PL ratio was raised. DEER measurements did not reveal specific aggregates of melittin, thus excluding the presence of stable, well-defined pore structures. In terms of membrane properties, the CW EPR reported reduced mobility in both polar head and alkyl chain regions with increasing P/PL. ESEEM measurements showed that, as the P/PL ratio increased, a small increase in water content in the PL headgroup region took place and no change was observed in the alkyl chains part close to the hydrophilic region. In terms of lipid local density, opposite behavior was observed for the polar head and alkyl chain regions with increasing P/PL; while the DPPC density increased in the polar head region, it decreased in the alkyl chain region. These results are consistent with disruption of the lipid order and segregation of the PL constituents of the membrane as a consequence of the melittin binding. This work further demonstrates the applicability and potential of pulse EPR techniques for the study of peptide-membrane interactions. PMID- 22091897 TI - Anesthesia and myasthenia gravis. AB - Myasthenia gravis (MG) is a disease affecting the nicotinic acetylcholine receptor of the post-synaptic membrane of the neuromuscular junction, causing muscle fatigue and weakness. The myasthenic patient can be a challenge to anesthesiologists, and the post-surgical risk of respiratory failure has always been a matter of concern. The incidence and prevalence of MG have been increasing for decades and the disease is underdiagnosed. This makes it important for the anesthesiologist to be aware of possible signs of the disease and to be properly updated on the optimal perioperative anesthesiological management of the myasthenic patient. The review is based on electronic searches on PubMed and a review of the references of the articles. The following keywords were used: myasthenia gravis AND neuromuscular blocking agents, myasthenia gravis AND sevoflurane, myasthenia gravis AND epidural, myasthenia gravis AND neuromuscular blockade reversal and myasthenia gravis AND pyridostigmine. The articles included were from reviews and clinical trials written in English. MG patients can easily be anesthetized without need for post-surgery mechanical ventilation whether it is general anesthesia or peripheral nerve block. Volatile anesthesia or the use of an epidural for the patient makes it possible to avoid the use of neuromuscular blocking agents, and when used, it should be in smaller doses and the patient should be carefully monitored. This review shows that with thorough pre-operative evaluation, continuing the daily pyridostigmine and careful monitoring the MG patient can be managed safely. PMID- 22091898 TI - Bisphosphonates and osteonecrosis of the jaw. AB - Bisphosphonates are used worldwide as a successful treatment for people with osteoporosis, which is the major underlying cause of fractures in postmenopausal women and older adults. These agents are successful at increasing bone mass and bone trabecular thickness, decreasing the risk of fracture, and decreasing bone pain, enabling individuals to have better quality of life. Bisphosphonates are also used to treat multiple myeloma, bone metastasis, and Paget's disease; however, bisphosphonate treatment may result in negative side effects, including osteonecrosis of the jaw (ONJ). ONJ involves necrotic, exposed bone in the jaw, pain, possible secondary infection, swelling, painful lesions, and various dysesthesias, although less-severe cases may be asymptomatic. First-generation bisphosphonates, which do not contain nitrogen, are metabolized into a nonfunctional, cytotoxic analogue of adenosine triphosphate and cause osteoclast death by starvation. Second-generation bisphosphonates are nitrogen-containing agents; these inhibit osteoclast vesicular trafficking, membrane ruffling, morphology, and cytoskeletal arrangement by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. Physicians treating older adults with osteoporosis and cancer should work together with dental practitioners, pharmacists, and other clinicians to inform individuals receiving bisphosphonates of their possible side effects and to suggest precautionary steps that may minimize the risk of osteonecrosis, particularly of the jaw. These include practicing good oral hygiene; scheduling regular dental examinations and cleanings; and cautioning people who are scheduling treatment for periodontal disease, oral and maxillofacial therapy, endodontics, implant placement, restorative dentistry, and prosthodontics. Recommendations for management of people with ONJ include an oral rinse, such as chlorhexidine, and antibiotics. PMID- 22091902 TI - Approach for prostate cancer vaccine development. PMID- 22091904 TI - Conscientiousness in the classroom: a process explanation. AB - Although the research literature has established that Conscientiousness predicts task performance across a variety of achievement contexts (e.g., ; ), comparatively less is known about the processes that underlie these relations. To the latter end, the current research examines effortful strategies and achievement goals as mediating factors that might explain why people with higher levels of Conscientiousness are predicted to reach higher levels of academic performance. In a longitudinal study, 347 college students completed measures of personality and achievement goals at the beginning of the class, followed by measures of effortful strategies multiple times throughout the semester. Results support the hypothesis that effortful strategies mediate the association between Conscientiousness and academic performance. Moreover, the statistical effects of Conscientiousness were generally independent of achievement goals, but a small portion of the effect was mediated through approach, not avoidance, achievement goals. These results highlight the importance of examining mediating processes between personality and outcomes, and in the case of Conscientiousness, our results suggest that effortful strategies might serve as a useful target for performance-enhancing interventions. PMID- 22091905 TI - Influence of durotomy on laser-Doppler measurement of spinal cord blood flow in chondrodystrophic dogs with thoracolumbar disk extrusion. AB - OBJECTIVES: To assess influence of durotomy on spinal cord blood flow (SCBF) in chondrodystrophic dogs with thoracolumbar disk extrusion. STUDY DESIGN: Prospective cohort study. ANIMALS: Chondrodystrophic dogs with thoracolumbar disk extrusion (n = 11). METHODS: Diagnosis was based on neurologic signs, magnetic resonance imaging (MRI) findings, and surgical confirmation. Regional SCBF was measured 3 times intraoperatively by laser-Doppler flowmetry: (1) before surgical decompression; (2) immediately after decompression by hemilaminectomy-durotomy; and (3) after 15 minutes of lesion lavage. A standardized hemilaminectomy and durotomy performed by the same neurosurgeon, was used to minimize factors that could influence measurement readings. RESULTS: A significant increase in intraoperative SCBF was found immediately after spinal cord decompression and durotomy in dogs but SCBF returned to previous levels or lower after 15 minutes of lavage. Changes in SCBF were not associated with duration of clinical signs; neurologic status, degree of spinal cord compression, or signal intensity changes as assessed by MRI. CONCLUSION: Durotomy does not increase SCBF in dogs with disk extrusion associated spinal cord compression. PMID- 22091906 TI - Total synthesis and stereochemical assignment of burkholdac B, a depsipeptide HDAC inhibitor. AB - Three diastereomers of burkholdac B were prepared by total synthesis, enabling the full stereochemical assignment of the natural product. It is proposed that burkholdac B is identical to thailandepsin A independently isolated by Cheng from the same strain of Burkholderia thailandensis . Burkholdac B is the most potent among depsipeptide histone deacetylase inhibitors in growth inhibition of the MCF7 breast cancer cell line with an IC(50) of 60 pM. PMID- 22091907 TI - Aiming for the bull's eye: Preparing for throwing investigated with event-related brain potentials. AB - We explored the feasibility of investigating complex goal-directed actions with event-related brain potentials by studying the aiming phase of throwing. A virtual reality environment was set up, allowing aimed throws at distant targets, with participants standing upright and moving relatively unrestrained. After a separate practice session, the contingent negative variation (CNV) was measured during preparation for a simple button release, unaimed throws, and aimed throws at targets of two levels of difficulty. Consistent with expectations, CNV amplitude was larger for all throwing conditions compared to button release. It further increased with task difficulty in the aimed throwing conditions, reflecting the increasing motor programming demands for more difficult goal directed actions. Therefore, investigating throwing as an instance of complex goal-directed action with ERPs is feasible, opening interesting perspectives for future research. PMID- 22091908 TI - The sensitivity of adverse event cost estimates to diagnostic coding error. AB - OBJECTIVE: To examine the impact of diagnostic coding error on estimates of hospital costs attributable to adverse events. DATA SOURCES: Original and reabstracted medical records of 9,670 complex medical and surgical admissions at 11 hospital corporations in Ontario from 2002 to 2004. Patient specific costs, not including physician payments, were retrieved from the Ontario Case Costing Initiative database. STUDY DESIGN: Adverse events were identified among the original and reabstracted records using ICD10-CA (Canadian adaptation of ICD10) codes flagged as postadmission complications. Propensity score matching and multivariate regression analysis were used to estimate the cost of the adverse events and to determine the sensitivity of cost estimates to diagnostic coding error. PRINCIPAL FINDINGS: Estimates of the cost of the adverse events ranged from $16,008 (metabolic derangement) to $30,176 (upper gastrointestinal bleeding). Coding errors caused the total cost attributable to the adverse events to be underestimated by 16 percent. The impact of coding error on adverse event cost estimates was highly variable at the organizational level. CONCLUSIONS: Estimates of adverse event costs are highly sensitive to coding error. Adverse event costs may be significantly underestimated if the likelihood of error is ignored. PMID- 22091909 TI - New estimates of fertility and child mortality in Africa, south of the Sahara. AB - Summary Earlier work by Page and Coale has estimated demographic indices of fertility and mortality for parts of Africa using the Sullivan modification of Brass's technique. The present paper presents modified and more accurate estimates of fertility and child mortality, not only for the sub-national units covered by Page and Coale but also for areas not covered by them. The present analysis which employs Trussell's refinement of Brass and Sullivan's techniques also includes improvements overlooked in earlier estimates. The salient finding that emerges is that while the Brass mortality technique is very powerful, his equally ingenious fertility technique is very weak and should not be relied on for estimating fertility parameters. PMID- 22091910 TI - The evolution of family planning in an African city: Ibadan, Nigeria. AB - Summary Data drawn from a 1973 probability sample of 6,606 Yoruba females, 15 59 years of age in Ibadan City, Nigeria, are employed to analyse changing family planning practice over time. Usage and method rates are calculated for broad age groups from 1930 to 1973. Contraceptive practice is shown to have increased rapidly during the 1960s and early 1970s, from a very low initial base with a doubling period for the proportion of contraceptors of about four years, so that by 1973 one-sixth of the women had practised contraception and one-ninth were currently doing so. The major determinant of contraceptive practice is education. Oral contraceptives and IUDs account for an ever larger proportion of all contraception over time and together made up over 50 per cent by 1973. The Ibadan data give strong support to a suggestion emanating from scattered findings elsewhere that there is a special pattern of sub-Saharan contraceptive use: it begins with use in pre-marital and extra-marital relationships; then is increasingly employed as a substitute for post-marital sexual abstinence, and only later becomes the means for limiting the size of the family. Hence, the success of a family planning programme is indicated by rising average parity among the acceptors. Most couples in Ibadan will probably be practising contraception at some time in the 1980s, but even then such rates will probably still be low in rural areas. PMID- 22091911 TI - Minority status and family size: A comparison of explanations. AB - Summary In this study, the family sizes of Chinese, Japanese and Filipino Americans are compared with those of whites, using data from the 1970 public use samples for California and Hawaii. The two hypotheses derived from the 'minority status' hypothesis are tested; the latter states that minorities experience tensions and anxiety which lead to lower fertility compared with native whites of Anglo-Saxon ancestry under certain conditions. We also examine the effect of assimilation in terms of variables known to affect fertility, and control for several age and acculturation variables. Analysis, based on a regression decomposition model, gives some support to the argument that the family size of minority groups differs from that of native whites because of incomplete assimilation and because independent variables affect fertility differently. However, since the independent effect of minority status per se is generally to raise fertility for Japanese and Chinese Americans, and lower it for Filipinos, we reject this version of the minority status hypothesis. Our general conclusion is that family size differentials in a pluralistic society may be part of a persisting pattern of sub-cultural differentiation, and do not necessarily reflect any 'tensions and anxiety' of minority status. PMID- 22091912 TI - Fertility decline in Germany: An econometric appraisal. AB - Summary A re-analysis of Knodel's data provides some new results for the fertility decline in Germany and a new approach to testing hypotheses about the demographic transition. Two formulations of transition theory are compared: one emphasizing the importance of changing social and economic structure for fertility decline; the other, the changing relationships between fertility and its determinants over time. To evaluate these formulations, multivariate time series cross-sectional models are developed. The statistical models permit the estimation of relationships both cross-sectionally and over time. As a consequence, the ability of the independent variables to explain cross-sectional as against temporal differences is evaluated. Industrialization, urbanization, religious composition, migration, infant mortality and marriage patterns satisfactorily explain the fertility decline once regional differences have been taken into account. Persisting characteristics of regional units account for much of the unexplained variance. Industrialization is the main explanatory variable of fertility decline in Germany. In the period considered, its impact on fertility increased substantially. PMID- 22091913 TI - Population momentum: A wider definition. AB - Summary Keyfitz has derived an elegant formula for estimating the ultimate size of an initially stable, growing population that abruptly reduces its fertility to replacement level. Reduction of fertility is achieved by the rather unrealistic device of dividing the original age schedule nffertility rates by the net reproduction rate. Only the inertia of the age distribution is thus accounted for, but not that of the fertility schedule. The key idea of an abrupt imposition of a fixed regimen capable in the long run of generating zero population growth may be retained, but the regimen made more realistic. By elaborating the population setting, such disparate ZPG regimens as reduction of marital fertility by contraception, delayed and/or less universal marriage, raised mortality risks, or permanent net out-migration may be formulated. Convergence of the populaton to stationarity becomes a two-phase process: a primary adjustment period of changing fertility rates followed by a period of age adjustment. The present paper treats what happens when a fixed ZPG sterilization regimen, defined by a minimum age of sterilization gamma and constant continuous risk phi of sterilization among unsterilized wives aged gamma to beta, is imposed abruptly (or else progressively over an interval T) upon an initially stable, growing population. Additional sources of residual growth are: (1) the nine-month lag in sterilization effect owing to pregnancy: (2) the more youthful pattern of child bearing under sterilization: (3) the extra adjustment period (of length beta gamma-0.75) of changing fertility rates; and (4) any delays in exposing elements of the population to the sterilization regimen. Two questions are pursued. First, how important are the additional sources of residual growth? Secondly, how do their relative sizes vary as a function of the characteristics of the initial population? PMID- 22091914 TI - The United Kingdom's international migration in the inter-war period: Theoretical considerations and empirical testing. AB - Summary At the theoretical level, the paper has two aims: to develop a three country migration model and to incorporate British emigration schemes of the 1920s into it. The model is tested on data of U.K. emigration to Canada, the U.S.A. and Australia from 1920 to 1936. PMID- 22091915 TI - Comment on 'facts and artifacts in the study of intra-uterine mortality: a reconsideration from pregnancy histories' by henri leridon(1). AB - Abstract Extract I have suggested that at a given birth order the probability of having a further pregnancy is greater when the last pregnancy had been spontaneously aborted than when it resulted in a birth.(2) Leridon,(3)in the course of a valuable paper on foetal wastage, presents data which, according to him, impugn my suggestion. I would like to question his claim. PMID- 22091916 TI - A reply to W. H. James. AB - Abstract The objection of W. H. James to my computation on p. 330, for the sample of Creteil, is valid. For reasons that are developed elsewhere in my paper, the current pregnancy of any woman was omitted in the elaboration of Table 6. Therefore, in order to derive continuation rates, we must re-include this pregnancy in each individual pregnancy history. Since women whose previous pregnancies ended in induced abortions had been excluded, we must do the same for women whose current pregnancy was interrupted by an induced abortion. PMID- 22091917 TI - Dual record demographic surveys: A re-assessment. AB - Summary A Review of 'Population Growth Estimation': A Handbook of Vital Statistics Measurement, by Eli S. Marks, W. Seltzer and K. J. Krotki. pp. 496. PMID- 22091918 TI - Notes to authors on the preparation of papers submitted to population studies. AB - Abstract All typing, including footnotes, references, extracts and quotations to be double-spaced and on one side of the paper which should preferably be A4 in size. PMID- 22091922 TI - Does decreased access to emergency departments affect patient outcomes? Analysis of acute myocardial infarction population 1996-2005. AB - OBJECTIVE: We analyze whether decreased emergency department (ED) access results in adverse patient outcomes or changes in the patient health profile for patients with acute myocardial infarction (AMI). DATA: We merge Medicare claims, American Hospital Association annual surveys, Medicare hospital cost reports, and location information for 1995-2005. STUDY DESIGN: We define four ED access change categories and estimate a ZIP Code fixed-effects regression models on the following AMI outcomes: mortality rates, age, and probability of percutaneous transluminal coronary angioplasty (PTCA) on day of admission. PRINCIPAL FINDINGS: We find a small increase in 30-day to 1-year mortality rates among patients in communities that experience a <10-minute increase in driving time. Among patients in communities with >30-minute increases, we find a substantial increase in long term mortality rates, a shift to younger ages (suggesting that older patients die en route), and a higher probability of immediate PTCA. Most of the adverse effects disappear after the transition years. CONCLUSIONS: Deterioration in geographic access to ED affects a small segment of the population, and most adverse effects are transitory. Policy planners can minimize the adverse effects by providing assistance to ensure adequate capacity of remaining EDs, and facilitating the realignment of health care resources during the critical transition periods. PMID- 22091921 TI - Cardiometabolic effects in caregivers of nursing home placement and death of their spouse with Alzheimer's disease. AB - OBJECTIVES: To test the hypothesis that cardiometabolic risk is attenuated when caregivers are relieved of caregiving stress when the caregiving recipient transitions out of the home. DESIGN: Longitudinal. SETTING: Participants' homes. PARTICIPANTS: One hundred nineteen spousal caregivers of a patient with Alzheimer's disease (AD) and 55 noncaregiving controls (mean age of entire sample 75 +/- 8, 68% women). MEASUREMENTS: Participants underwent up to three yearly assessments of metabolic syndrome (MetS) factors related to adiposity, dyslipidemia, hypertension, and hyperglycemia. Changes in the total number of MetS factors (range: 0-5) 3 months after caregiver transitions were evaluated using random regression models with fixed and time-variant effects for sociodemographic and health-related covariates. RESULTS: Caregivers had a greater number of MetS factors over time than noncaregivers (1.78 +/- 0.13 vs 1.36 +/- 0.18, P = .008), which, after the death of the spouse, dropped by 0.46 +/- 0.16 (P = .003) being no longer different from those of noncaregivers; this effect was most prominently related to decreases in triglycerides (-22.2 +/- 11.0 mg/dL, P = .03), systolic blood pressure (-6.2 +/- 2.6 mmHg, P = .02), and diastolic blood pressure (-3.4 +/- 1.5 mmHg, P = .03). Placement of the spouse decreased the number of MetS factors only in caregivers with lower levels of depressive symptoms (-0.48 +/- 0.18, P = .01) and sleeping difficulties (-0.42 +/- 0.18, P = .02) but not in caregivers with higher levels in these measures at postplacement. CONCLUSION: High cardiometabolic risk in caregivers decreased to the level of that of noncaregivers within 3 months of death of the spouse with AD, although placement, a transition in the course of dementia caregiving, did not benefit cardiovascular health in highly distressed caregivers. PMID- 22091923 TI - Investigation of nanoparticle transport inside coarse-grained geological media using magnetic resonance imaging. AB - Quantifying nanoparticle (NP) transport inside saturated porous geological media is imperative for understanding their fate in a range of natural and engineered water systems. While most studies focus upon finer grained systems representative of soils and aquifers, very few examine coarse-grained systems representative of riverbeds and gravel based sustainable urban drainage systems. In this study, we investigated the potential of magnetic resonance imaging (MRI) to image transport behaviors of nanoparticles (NPs) through a saturated coarse-grained system. MRI successfully imaged the transport of superparamagnetic NPs, inside a porous column composed of quartz gravel using T(2)-weighted images. A calibration protocol was then used to convert T(2)-weighted images into spatially resolved quantitative concentration maps of NPs at different time intervals. Averaged concentration profiles of NPs clearly illustrates that transport of a positively charged amine-functionalized NP within the column was slower compared to that of a negatively charged carboxyl-functionalized NP, due to electrostatic attraction between positively charged NP and negatively charged quartz grains. Concentration profiles of NPs were then compared with those of a convection-dispersion model to estimate coefficients of dispersivity and retardation. For the amine functionalized NPs (which exhibited inhibited transport), a better model fit was obtained when permanent attachment (deposition) was incorporated into the model as opposed to nonpermanent attachment (retardation). This technology can be used to further explore transport processes of NPs inside coarse-grained porous media, either by using the wide range of commercially available (super)paramagnetically tagged NPs or by using custom-made tagged NPs. PMID- 22091924 TI - Titan tholins: simulating Titan organic chemistry in the Cassini-Huygens era. PMID- 22091925 TI - Beyond seizures and medications: normal activity limitations, social support, and mental health in epilepsy. AB - Although seizure control is a critical goal for persons with epilepsy (PWE) from the biomedical perspective, there is growing support for approaches that take into account the effect of epilepsy on the whole person (the biopsychosocial perspective). We hypothesized that PWE who report normal activity limitations due to epilepsy and poor social/emotional support would report poor mental health regardless of whether they report having seizures in the past 3 months or currently taking medication for their epilepsy. In 2005 and 2006, twenty-two states asked about epilepsy in the Behavioral Risk Factor Surveillance System (BRFSS). A set of survey weight-adjusted logistic regression analyses were conducted to examine self-reported poor mental health. Our findings reveal that both normal activity limitations due to epilepsy and poor social/emotional support are significant predictors of reporting poor mental health. After controlling for social support, demographics, comorbidities, and health behaviors we determined that those reporting normal activity limitations due to epilepsy are more likely to report poor mental health (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.41-6.58). Similarly, after controlling for the same factors, PWE with poor social/emotional support are more likely to report poor mental health (OR 3.22, 95% CI 1.84-5.61). In contrast, reported seizures in the past 3 months (OR 1.12, 95% CI 0.56-2.25) or current use of medication (OR 0.58, 95% CI 0.30-1.10) were not significantly associated with poor mental health. These population-based findings support the need for clinical approaches that address psychosocial issues in addition to seizure control and treatment. PMID- 22091926 TI - Eyeblink conditional discrimination learning in healthy young men is impaired after stress exposure. AB - Stress is known to influence the hippocampus. Eyeblink conditional discrimination learning is dependent on the hippocampus, but the effects of stress on the task are unknown. Male participants were allocated to a psychosocial stress condition (Trier Social Stress Test) or a control condition. Afterwards, a conditional discrimination task was performed. A tone (the CS) predicted an airpuff (the US) only when preceded by a specific visual stimulus (a red or a green colored square, the S+ and S-). Stressed participants showed a rise in cortisol and an increase in negative affect. Stressed participants also failed to acquire the conditional discrimination. They responded to all of the presented CS irrespective of the preceding occasion setter (S+ or S-). Controls, in contrast, acquired the discrimination rapidly. The present study provides further evidence for an impairing effect of acute stress on tasks relying on the hippocampal formation. PMID- 22091927 TI - Intercepting bacterial indole signaling with flustramine derivatives. AB - Indole signaling is one of the putative universal signaling networks in bacteria. We have investigated the use of desformylflustrabromine (dFBr) derivatives for the inhibition of biofilm formation through modulation of the indole-signaling network in Escherichia coli and Staphylococcus aureus . We have found dFBr derivatives that are 10-1000 times more active than indole itself, demonstrating that the flustramine family of indolic natural products represent a privileged scaffold for the design of molecules to control pathogenic bacterial behavior. PMID- 22091928 TI - Ecology of Borrelia burgdorferi sensu lato in Europe: transmission dynamics in multi-host systems, influence of molecular processes and effects of climate change. AB - The analysis of different multi-host systems suggests that even hosts that are not capable of transmitting Borrelia burgdorferi sensu lato (s.l.) to the tick vector, Ixodes ricinus, or that are secondary reservoirs for these agents contribute to the intensity of transmission and to the overall risk of Lyme borreliosis, through the process of vector augmentation and pathogen amplification. On the other hand, above certain threshold densities, or in the presence of competition with primary reservoir hosts or low attachment rate of ticks to reservoir hosts, incompetent or less competent hosts may reduce transmission through dilution. The transmission of B. burgdorferi s.l. is affected by molecular processes at the tick-host interface including mechanisms for the protection of spirochaetes against the host's immune response. Molecular biology also increasingly provides important identification tools for the study of tick-borne disease agents. Ixodes ricinus and B. burgdorferi s.l. are expanding their geographical range to northern latitudes and to higher altitudes through the effects of climate change on host populations and on tick development, survival and seasonal activity. The integration of quantitative ecology with molecular methodology is central to a better understanding of the factors that determine the main components of Lyme borreliosis eco-epidemiology and should result in more accurate predictions of the effects of climate change on the circulation of pathogens in nature. PMID- 22091929 TI - The introduction of a choice to learn pre-symptomatic DNA test results for BRCA or Lynch syndrome either face-to-face or by letter. AB - In predictive DNA testing for hereditary cancer, test results should traditionally be disclosed face-to-face. Increasingly, however, counselees ask to receive their test result at home by letter. To compare the quality of genetic counselling in the traditional way to a procedure in which counselees are offered a choice on how to get their test result. Counselees from families with a known BRCA1/2 or Lynch syndrome mutation were randomised into two groups. The control group was given the DNA test result in a face-to-face consultation. In the intervention group people could choose to learn their test result face-to-face or by letter. The quality of genetic counselling was assessed through questionnaires at three different moments. Data of 198 counselees were analysed. The quality of genetic counselling and psychological functioning were equally good in both groups. The majority of cases chose for disclosure by letter. The counselees with a good test result in the intervention group were the most satisfied. Our results indicate that in predictive DNA testing for BRCA1/2 and Lynch syndrome, a choice protocol is equally safe and more satisfying. Moreover, it is more efficient for both counsellor and counselee. PMID- 22091930 TI - Comparative evaluation of pharmaceutical products obtained in Mexico: augmenting existing scientific data. AB - CONTEXT: The accessibility of pharmacies in neighboring countries has facilitated the trend of acquiring medications outside of local borders. However, scientific data assessing the drug content and quality of these medications has not increased in a corresponding fashion. OBJECTIVE: This study seeks to augment existing scientific data. MATERIALS AND METHODS: Seventeen products that were obtained from pharmacies in Mexico were evaluated for active ingredient content. The active pharmaceutical ingredients (API) assessed included amoxicillin, ampicillin, ciprofloxacin, levothyroxine, sildenafil citrate, sulfamethoxazole, trimethoprim, and warfarin. API content was analysed with high performance liquid chromatography assays and the resultant data interpreted by applying United States Pharmacopeia (USP) acceptability limits. RESULTS: All of the samples analyzed for the two ciprofloxacin products and the two ampicillin products were found to be within the USP limits. Of the four different sulfamethoxazole/trimethoprim products tested, all were within USP limits for sulfamethoxazole, but contained 2-3 individual units which were outside of USP limits for trimethoprim. Several of the remaining products (amoxicillin, levothyroxine, sildenafil citrate, and warfarin) had individual units that fell outside of the USP limits, although only one of the levothyroxine products (1 out of 20 tablets tested) and both sildenafil citrate products (all of the units tested) contained units outside of +/-25% label claim. PMID- 22091931 TI - The S-measurement in the diagnosis of canine hip dysplasia. AB - OBJECTIVE: To propose a direct measure of subluxation of the femoral head (S) in the assessment of hip joint laxity and evaluate it for clinical use. STUDY DESIGN: Method comparison study. ANIMALS: Dogs (n = 51). METHODS: Dogs were sedated or anesthetized for a dorsolateral subluxation (DLS) examination. Two sets of radiographs were acquired, 1 each by a different technologist. A calibrated measuring bar was included on the image at the height of the hip to assess magnification. The DLS was calculated for each hip and different persons unaware of these details measured the "S"-value. One person measured the S-value 3 times over 3 days. Box plots were used to determine a cut-off for the empiric (8 mm) and corrected (4 mm) S-value. RESULTS: Of 51 dogs, 33 were dysplastic based on a DLS score <55%. Magnification and body weight were strongly correlated (r = 0.4922, P = .0006). Both empiric and corrected S measurements showed good agreement with the DLS score (kappa = 0.688 and kappa = 0.681, respectively). The corrected S measurement produced more false negatives. Bland-Altman analysis showed interobserver and technician variance acceptable for clinical use (limits of agreement < +/-3 mm). Intraobserver repeatability was acceptable for the right hip (95% of differences were <=1.3 mm and 100% <= 1.9) but not for the left hip. CONCLUSION: Using a cut-off value of 5 mm, the empirical S measurement can be used to exclude hip dysplasia in young dogs of various body proportions. PMID- 22091932 TI - Physician perspectives on medical care delivery in assisted living. AB - OBJECTIVES: To describe the provision of medical care in assisted living (AL) as provided by physicians who are especially active in providing care to older adults and AL residents; to identify characteristics associated with physician confidence in AL staff; and to ask physicians a variety of questions about their experience providing care to AL residents and how it compares with providing care in the nursing home and home care settings. DESIGN: Cross-sectional descriptive study. SETTING: AL communities in 27 states. PARTICIPANTS: One hundred sixty-five physicians and administrators of 125 AL settings in which they had patients. MEASUREMENTS: Interviews and questionnaires containing open- and close-ended questions regarding demographics, care arrangements, attitudes, and behaviors in managing medical problems. RESULTS: Most respondents were certified in internal medicine (46%) or family medicine (47%); 32% were certified in geriatrics and 30% in medical directorship. In this select sample, 48% visited the AL setting once a year or less, and 19% visited once a week or more. Mean physician confidence in AL staff was 3.3 (somewhat confident), with greater confidence associated with smaller AL community size, nursing presence, and the physician being the medical director. Qualitative analyses identified differences between settings including lack of vital sign assessment in the home setting, concern about the ability of AL staff to assess and monitor problems, and greater administrative and regulatory requirements in AL than in the other settings. CONCLUSION: Providing medical care for AL residents presents unique challenges and opportunities for physicians. Nursing presence and physician oversight and familiarity and communicating with AL staff who are highly familiar with a given resident and can monitor care may facilitate care. PMID- 22091933 TI - The bystander effect is a novel mechanism of UVA-induced melanogenesis. AB - We successfully identified the bystander effect in B16 murine melanoma cells exposed to UVA irradiation. The effect was identified based on melanogenesis following the medium transfer of the B16 cells, which had been cultured for 24 h after being exposed to UVA irradiation, to nonirradiated cells (bystander cells). Our confirmation study of the functional mechanism of bystander cells confirmed the reduced levels of mitochondrial membrane potential 1-4 h after the medium transfer. In addition, we observed increased levels of intracellular oxidation after 9-12 h, and the generation of melanin radicals, including long-lived radicals, 24 h after medium transfer. Further analysis of bystander factors revealed that the administration of EGTA treatment at the time of medium transfer led to an inhibition of melanogenesis and to neutralization of the mitochondrial membrane potential level, as well as to the restoration of intracellular oxidation levels to those of controls. The results demonstrated that the UVA irradiation bystander effect in B16 cells, as indicated by melanogenesis, was induced by the increase in intracellular oxidation due to the mitochondrial activity of calcium ions, which were among the bystander factors involved in the increase. PMID- 22091934 TI - Family composition preferences in a developing culture: The case of Taiwan, 1973. AB - Abstract As fertility comes increasingly under voluntary control in a developing society, it can be argued that individual desires or preferences about children will become more salient and more significant for eventual fertility. Hence, the study of preferences is increasingly important as contraceptive use is extended and results in decreasing the number of unwanted births.(1) Further changes in fertility then depend on changes in preferences. The assumption is that people will at least try to achieve the families they want, if the means to do so are available. The fact that contraception is used at all is some evidence of the soundness of this assumption, although it should be recognized that family size desires operate in a complex of preferences, under varying degrees of conflict and control. To expect a one-to-one relationship between attitudes or preferences and overt behaviour would be simplistic. PMID- 22091935 TI - Household composition and extended kinship in Taiwan. AB - Abstract The extended family has been an essential part of Chinese society, both in cultural ideal and social reality.(1) The traditional Chinese ideal has been for co-residence of parents with their married sons and their families in a large, joint-stem household unit. The reality, in Taiwan and elsewhere, has deviated from the ideal in several ways. First, for any given young couple, relatives necessary for a joint-stem family may not be available at one or another stage of the family life cycle. Secondly, even when all the necessary relatives are available, the emphasis has been on the vertical filial tie, rather than the horizontal fraternal tie, so the predominant fact has been co-residence of parents with a married son. Married brothers usually-do not live together and, if they do, it is usually when the parent is or has been in the same unit. PMID- 22091936 TI - Effects of child mortality on subsequent fertility of women in some rural and semi-urban areas of certain Latin American countries. AB - Abstract With the rapid decline in child mortality in developing countries there is considerable interest in understanding its effects on fertility. According to the theory of demographic transition, mortality declines are accompanied by fertility declines after a time lag, as countries go through the process of economic development. However, the immediate effects of a mortality decline on fertility have not been uniform as in many countries fertility has actually increased. For example, in many Latin American countries where mortality declines have been very rapid there have not been any appreciable changes in fertility. Only in recent years has there been a noticeable decline in the urban areas of some nations. While it is possible to examine the effects of various socio-economic factors on mortality and fertility at the macro-level, any real understanding of how mortality itself influences fertility would require information at the micro-level on couples who have experienced child mortality and who are also exposed to the risk of childbearing. PMID- 22091937 TI - How a trend towards a stationary population affects consumer demand. AB - Abstract During the great depression of the 1930seconomists in both the United States and Europe tried to analyse the economic consequences of declining rates of population growth. Not only were birth rates in many industrial countries at the lowest levels ever, but they coincided with high rates of unemployment. Of the many economists who held that demographic trends were partly responsible for the adverse economic conditions, a prominent example was John Maynard Keynes. According to his so-called stagnation thesis, population growth stimulates investment demand in two ways: more people need more goods and services and, hence, more investment in factories and machinery; and with population growing, businessmen are more likely to regard their investment misallocations as less serious than when the growth is slow or nil.(1)A minority of writers were more optimistic about the economic consequences of slower rates of population growth. For example, Thompson argued that with a lower ratio of consumers to producers the population would enjoy a higher standard of living and the education of children should improve.(2). PMID- 22091938 TI - Fertility, mortality, migration and family planning in the Yemen Arab Republic. AB - Abstract Until the end of the seven years' civil war following the revolution of 1962, almost no reliable statistical information of any kind about the Yemen Arab Republic (North Yemen) and its people was available. Since President al Hamdi's takeover of 1974, the demand for more accurate statistics for developing planning has led to a number of studies which give us the first numerical insights into the dynamics of the Yemen's population. The National Population Census of 1975 is the most important of these studies since it showed two things very clearly. First, it indicated that the Yemen's population is large and concentrated in selected rural areas where there are real problems of crowding and shortages of good agricultural land. Secondly, the Census showed that the lack of domestic economic opportunities partially related to the high rural population densities, and the numerous opportunities in the oil-rich states of the Middle East, especially Sa'udi Arabia, had resulted in an out-migration of young males of prime ages of very large proportions. This article elaborates further on the dynamics of the population in Yemen and reports on the results of a small sample survey carried out in May 1976which provides further insights into the factors affecting fertility and mortality during this early stage of the Yemen's economic and social development. PMID- 22091939 TI - Consistency between fertility attitudes and behaviour: A conceptual model. AB - Abstract The consistency (or lack of it) between attitude and behaviour has been a controversial issue in social psychology for the past several decades,(1) and more recently has become a focus of considerable controversy in the field of population studies.(2) In accordance with Freedman, Hermalin and Chang,(3)it is argued here that this controversy will not be resolved by theoretical discussions, and evidence is needed from many countries at several time points to resolve this issue. This paper presents evidence on consistency between fertility attitudes and behaviour from survey data from Venezuela and, based upon analysis of the present data, suggests a conceptual model for the study of consistency between fertility attitudes and behaviour. PMID- 22091940 TI - The length of the human fertile period. AB - Abstract Estimates of the. length of the human fertile period (that interval within the menstrual cycle during which insemination is associated with a non zero probability of conception) are necessarily indirect. Moreover, those estimates do not seem in close agreement with one another. For instance, it has been suggested that: PMID- 22091941 TI - A comment on De Jong and Sell's 'Changes in childlessness in the United States: A demographic path analysis'. AB - Abstract I found De Jong and Sell's recent paper! to be a study in contrasts. On the one hand, the authors have done a good job of scouring the literature for information pertinent to their work. It is evident from the breadth of sources cited that they were both persistent and thorough in this task. I also found their discussions of possible explanations for changing patterns of childlessness to be very good. PMID- 22091945 TI - Erratum. PMID- 22091942 TI - Changes in childlessness for all women in the United States: A reply to Spencer. AB - Abstract The analysis of changes in childlessness as opposed to structural correlates of childlessness is quite new. Our focus on indicators of such changes called for a macro-analytic framework which would permit the test of changing features of population characteristics and the relationship between structural changes in different population cohorts. An appropriate data set was one that would permit the analysis ofchanging levels ofchildlessness in age cohorts and the changes in population characteristics which would offer possible explanations for the changing childlessness pattern. PMID- 22091946 TI - Establishing a trait anxiety threshold that signals likelihood of anxiety disorders. AB - Evidence suggests that the state trait inventory for cognitive and somatic anxiety (STICSA) may be a more pure measure of anxiety than other commonly used scales. Further, the STICSA has excellent psychometric properties in both clinical and nonclinical samples. The present study aimed to extend the utility of the STICSA-Trait version by identifying a cut-off score that could differentiate a group of clinically diagnosed anxiety disorder patients (n=398) from a group of student controls (n=439). Two receiver operating characteristic curve analyses indicated cut-off scores of 43 (sensitivity=.73, specificity=.74, classification accuracy=.74) and 40 (sensitivity=.80, specificity=.67, classification accuracy=.73), respectively. In a large community sample (n =6685), a score of 43 identified 11.5% of individuals as probable cases of clinical anxiety, while a score of 40 identified 17.0% of individuals as probable cases of clinical anxiety. As a result of differences in sensitivity and specificity, the present findings suggest a cut-off score of 43 is optimal to identify probable cases of clinical anxiety, while a cut-off score of 40 is optimal to screen for the possible presence of anxiety disorders. PMID- 22091947 TI - In situ methane recovery and carbon dioxide sequestration in methane hydrates: a molecular dynamics simulation study. AB - One intriguing idea for the simultaneous recovery of energy and sequestration of global warming gas is proposed by the transformation of methane hydrates to carbon dioxide hydrates with the injection of liquid CO(2). Here we use molecular dynamics simulations to show that the replacement can take place without melting of the network of hydrogen-bonded water molecules. Depending on the distance to the interface between the liquid CO(2) and solid clathrate hydrate, we find that the replacement occurs either via direct swapping of methane and CO(2) or via a transient co-occupation of both methane and CO(2) in one cavity. Our results suggest that, with a careful design of the operation condition, it is possible to replace methane from methane hydrates with CO(2) in the solid phase without much change in the geological stability. PMID- 22091948 TI - Exploring the personality structure in the 11 languages of South Africa. AB - The present study, part of the development of the South African Personality Inventory (SAPI), explores the implicit personality structure in the 11 official language groups of South Africa by employing a mixed-method approach. In the first, qualitative part of the study, semistructured interviews were conducted with 1,216 participants from the 11 official language groups. The derived personality-descriptive terms were categorized and clustered based on their semantic relations in iterative steps involving group discussions and contacts with language and cultural experts. This analysis identified 37 subclusters, which could be merged in 9 broad clusters: Conscientiousness, Emotional Stability, Extraversion, Facilitating, Integrity, Intellect, Openness, Relationship Harmony, and Soft-Heartedness. In the second, quantitative part, the perceived relations between the 37 subclusters were rated by 204 students from different language groups in South Africa and 95 students in the Netherlands. The outcomes generally supported the adequacy of the conceptual model, although several clusters in the domain of relational and social functioning did not replicate in detail. The outcomes of these studies revealed a personality structure with a strong emphasis on social-relational aspects of personality. PMID- 22091949 TI - Alpha-adrenergic receptor gene polymorphisms and cardiovascular reactivity to stress in Black adolescents and young adults. AB - Cardiovascular reactivity to stress and alpha-adrenergic receptor (alpha-AR) function may contribute to the development of hypertension. As Black Americans have an increased risk of hypertension, we evaluated associations between alpha(1A) -AR (Arg492Cys), alpha(2A) -AR (-1291C/G), and alpha(2B) -AR (Ins/Del301-303) gene variants and cardiovascular reactivity in 500 normotensive Black youth. Heart rate, preejection period, total peripheral resistance, and blood pressure were measured during cold and psychological stress. The Arg492Cys polymorphism in the alpha(1A) -AR gene was associated with heart rate reactivity to stress, but the association depended on sex. The -1291C/G promoter polymorphism in the alpha(2A) -AR gene was associated with vascular reactivity to stress; vasoconstriction increased as a linear function of the number of copies of the variant G allele. Thus, specific associations emerged between genetic variations in alpha-Ars and cardiovascular reactivity in young Blacks. PMID- 22091950 TI - Does community-based health insurance protect household assets? Evidence from rural Africa. AB - OBJECTIVE: To evaluate whether community-based health insurance (CBHI) protects household assets in rural Burkina Faso, Africa. DATA SOURCES: Data were used from a household panel survey that collected primary data from randomly selected households, covering 41 villages and one town, during 2004-2007(n = 890). STUDY DESIGN: The study area was divided into 33 clusters and CBHI was randomly offered to these clusters during 2004-2006. We applied different strategies to control for selection bias-ordinary least squares with covariates, two-stage least squares with instrumental variable, and fixed-effects models. DATA COLLECTION: Household members were interviewed in their local language every year, and information was collected on demographic and socio-economic indicators including ownership of assets, and on self-reported morbidity. PRINCIPAL FINDINGS: Fixed effects and ordinary least squares models showed that CBHI protected household assets during 2004-2007. The two-stage least squares with instrumental variable model showed that CBHI increased household assets during 2004-2005. CONCLUSIONS: In this study, we found that CBHI has the potential to not only protect household assets but also increase household assets. However, similar studies from developing countries that evaluate the impact of health insurance on household economic indicators are needed to benchmark these results with other settings. PMID- 22091951 TI - Incidence of medial meniscal tears after arthroscopic assisted tibial plateau leveling osteotomy. AB - OBJECTIVE: To determine the incidence of medial meniscal tears in dogs with naturally occurring cranial cruciate ligament (CCL) disease treated with arthroscopy and tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Retrospective case series. SAMPLE POPULATION: Canine Stifles (n = 357) with naturally occurring CCL disease. METHODS: Medical records (November 2006-November 2009) were reviewed for all dogs with CCL disease treated with arthroscopic CCL debridement, meniscal probing, and TPLO. We investigated the significance of the preoperative variables; age, weight, tibial plateau angle (TPA), sex, and the preoperative condition of the CCL on the prevalence of concurrent meniscal tears (CMT) and incidence of late onset meniscal tears (LMT). RESULTS: Prevalence of CMT and incidence of LMT was 32.2% and 5.6%, respectively. A significant difference between age of dogs with and without CMT was identified. There was a significantly lower prevalence of CMT and incidence of LMT in dogs that had a partial CCL tear compared with those that had a complete CCL tear. All dogs with LMT treated by partial meniscectomy (PMM) returned to peak postoperative limb function after (PMM) based on client-assessed outcomes. CONCLUSIONS: This study demonstrates the importance of LMT as a complication, the importance of comprehensive meniscal assessment, and may add to the evidence against routinely performing meniscal release in TPLO. The preoperative condition of the CCL should be considered before operating on grossly normal menisci. PMID- 22091952 TI - Synthesis of rhodamines from fluoresceins using Pd-catalyzed C-N cross-coupling. AB - A unified, convenient, and efficient strategy for the preparation of rhodamines and N,N'-diacylated rhodamines has been developed. Fluorescein ditriflates were found to undergo palladium-catalyzed C-N cross-coupling with amines, amides, carbamates, and other nitrogen nucleophiles to provide direct access to known and novel rhodamine derivatives, including fluorescent dyes, quenchers, and latent fluorophores. PMID- 22091956 TI - Regional cerebral blood flow and glucose metabolism during propofol anaesthesia in healthy subjects studied with positron emission tomography. AB - BACKGROUND: General anaesthetics can alter the relationship between regional cerebral glucose metabolism rate (rGMR) and regional cerebral blood flow (rCBF). With the present study, we wanted to assess quantitatively the effects of propofol on rCBF and rGMR in the same healthy volunteers measured with positron emission tomography (PET). METHODS: (15)O-labelled water and (18)F fluorodeoxyglucose were used as PET tracers to determine rCBF and rGMR, respectively, in eight healthy volunteers during the waking state (baseline) and during propofol anaesthesia. Propofol was titrated to keep a constant hypnotic depth (Bispectral Indes 35-40) throughout the anaesthesia. Changes in rGMR and rCBF were quantified using region-of-interest and voxel-based analyses. RESULTS: The measured mean propofol concentration was 4.1 +/- 0.8 MUg/ml during anaesthesia. Compared with the conscious state, total CBF and GMR decreased during the anaesthetic state with 47% and 54%, respectively. In the white and grey matter, rCBF and rGMR were reduced by 37% and 49%, and by 45% and 57%, respectively. Propofol decreased rCBF in all brain structures by 46-55% (P <= 0.01) with highest significant decreases in the thalamus and parietal lobe. Regional GMR was reduced in all brain areas to 48-66% (P <= 0.01) with highest significant reductions in the occipital lobe, the lingual gyrus, parietal lobe, temporal lobe and thalamus. No increases in rCBF or rGMR happened anywhere. CONCLUSIONS: General anaesthesia with propofol is associated with a global metabolic and vascular depression in the human brain, with significant shifts in regional blood flow and metabolism indicating marked metabolic and vascular responsiveness in some cortical areas and thalamus. PMID- 22091957 TI - Mobilization of manufactured gas plant tar with alkaline flushing solutions. AB - This experimental study investigates the use of alkaline and alkaline-polymer solutions for the mobilization of former manufactured gas plant (FMGP) tars. Tar aqueous interfacial tensions (IFTs) and contact angles were measured, and column flushing experiments were conducted. NaOH solutions (0.01-1 wt.%) were found to significantly reduce tar-aqueous IFT. Contact angles indicated a shift to strongly water-wet, then to tar-wet conditions as NaOH concentration increased. Column experiments were conducted with flushing solutions containing 0.2, 0.35, and 0.5% NaOH, both with and without xanthan gum (XG). Between 10 and 44% of the residual tar was removed by solutions containing only NaOH, while solutions containing both NaOH and XG removed 81-93% of the tar with final tar saturations as low as 0.018. The mechanism responsible for the tar removal is likely a combination of reduced IFT, a favorable viscosity ratio, and tar bank formation. Such an approach may have practical applications and would be significantly less expensive than surfactant-based methods. PMID- 22091958 TI - Concomitant use of cholinesterase inhibitors and anticholinergics: prevalence and outcomes. AB - OBJECTIVES: To determine the extent of concomitant use of cholinesterase inhibitor (ChI) and anticholinergic (ACh) medications and the clinical consequences of dual use in a population-based setting. DESIGN: Retrospective cohort study. SETTING: Group Health Cooperative and Kaiser Permanente Colorado. PARTICIPANTS: Five thousand six hundred twenty-five adults aged 50 and older who began new use of a ChI between 2000 and 2007. MEASUREMENTS: Rates and characteristics of concomitant ChI and ACh use and the association between dual use and the outcomes of death and nursing home placement (claim from a nursing home with no prior claims used as a proxy). RESULTS: Thirty-seven percent of ChI users also received AChs. Eleven percent of ChI users were concomitantly using two or more moderate to potent AChs. Median duration of this concomitant use was approximately 4 months, but a substantial proportion (25%) continued to use both medication classes simultaneously for longer than 12 months. In 23% of ChI users, AChs were being used at the time ChI therapy was initiated. The majority of this ACh use (77%) was not stopped once ChIs were started. No association was observed between concomitant use and risk of death or nursing home placement. CONCLUSION: These results should raise awareness about the prevalence and potential inappropriateness of concomitant use of ChIs and AChs and promote evaluations of practices intended to improve care standards. PMID- 22091959 TI - Incompletely condensed fluoroalkyl silsesquioxanes and derivatives: precursors for low surface energy materials. AB - A novel synthetic method was developed for the controlled functionalization of fluorinated polyhedral oligomeric silsesquioxanes (F-POSS), which are useful as low surface energy materials for superhydrophobic and superoleophobic materials. Utilizing triflic acid, open-cage compounds were created and then reacted with a variety of dichlorosilanes to produce functional F-POSS structures possessing alkyl-, aryl-, and acrylate-based moieties. The crystal structure for an endo,endo-disilanol F-POSS compound was determined by single-crystal X-ray diffraction. The chemical structures were confirmed using multinuclear NMR spectroscopy ((1)H, (13)C, (19)F, and (29)Si), FT-IR, and combustion analysis. Dynamic contact angle measurements of these compounds were taken with water and hexadecane. These novel structures were found to possess excellent wetting resistant behavior, similar to that of the parent F-POSS compound. They are the first well-defined fluorinated nano-building blocks with a controlled level of reactive functionality for the development of new superhydrophobic and superoleophobic materials. PMID- 22091960 TI - Translation of evidence-based clinical standards into a new prehospital resuscitation policy in Los Angeles County. AB - OBJECTIVE: To translate a set of evidence-based clinical standards designed to allow paramedics to forego unnecessary and potentially harmful resuscitation attempts into a feasible new policy. DATA SOURCES/SETTING: Policy documents, meeting minutes, and personal communications between a large urban Emergency Medical Services (EMS) agency serving all of Los Angeles County (LAC) and a research group were reviewed over 12 months. STUDY DESIGN: LAC EMS and University of California, Los Angeles (UCLA) formed a partnership (the EMS-UCLA Collaborative) to develop and translate the standards into new EMS protocols. Clinical indicators considered appropriate and feasible by an expert panel were submitted to the agency for inclusion in the new policy. FINDINGS: The Collaborative submitted the results to the LAC EMS Commission and a physician advisory group for review. Of the 41 indicators approved by the expert panel, 22 would have resulted in changes to the current policy. All six involved asking family members about or honoring written and verbal Do Not Attempt Resuscitate requests, but only 4 of the 16 indicators based on clinical characteristics were included in the new policy. Ultimately, 10 of the 22 indicators that would have changed policy were approved and implemented. CONCLUSIONS: By collaboration, a large EMS agency and a research team were able to develop and implement a revised resuscitation policy within 1 year. PMID- 22091961 TI - Task confusion after switching revealed by reductions of error-related ERP components. AB - While response delays after task switching have been widely used as an index to investigate the limits of cognitive flexibility, little is known about their counterpart in error rates. It has been hypothesized that at least some postswitching errors are not caused by simple response errors but by task confusion, which refers to the establishment and execution of an incorrect task set. The aim of the current study is to provide evidence for this hypothesis. Using a multitrial paradigm, we firstly dissociated task confusion from simple cue encoding failure, and then measured the error-related negativity (ERN) and the following error positivity (Pe) as indices of the brain's error processing. We predicted that task confusion, if it exists, would cause ambiguity to the criteria of correct response, and therefore attenuate error processing. Results confirmed our prediction, suggesting that task confusion actually occurs after switching. PMID- 22091963 TI - Absence of influenza A(H1N1) during seasonal and pandemic seasons in a sentinel nursing home surveillance network in the Netherlands. AB - OBJECTIVES: To describe the epidemiological, virological, and institutional characteristics of influenza-like illness (ILI) in nursing homes (NHs). DESIGN: Continuous clinical surveillance of ILI and virological surveillance of ILI and other acute respiratory infections (ARIs) during four influenza seasons. SETTING: National sentinel NH surveillance network. PARTICIPANTS: National sentinel residents. MEASUREMENTS: Weekly registration of ILI cases (influenza seasons 2008/09-2009/10), influenza virus detection (influenza seasons 2006/07-2009/10), and collection of institutional characteristics of NHs at start of participation. RESULTS: During the 2008/09 influenza season, ILI incidence started to rise in Week 49 of 2008, peaked in Week 3 of 2009 (158 cases per 10,000 resident weeks), and flattened out by Week 16 of 2009 (mean ILI incidence during epidemic: 73 cases per 10,000 resident weeks). During the 2009/10 influenza pandemic, there was no epidemic peak. Influenza virus type and subtype varied throughout virological surveillance but was limited to influenza A(H3N2) and B viruses. Higher staff vaccination coverage (>15%) was associated with lower ILI-incidence in the 2008/09 influenza season in a univariate negative binomial regression analysis (incidence rate ratio = 0.3, 95% confidence interval = 0.1-0.8)). CONCLUSION: Neither seasonal nor pandemic influenza A(H1N1) viruses were detected in the network, despite widespread community transmission of seasonal and influenza A(H1N1) virus. ILI incidence trends corresponded to virological trends. Sentinel surveillance of ILI combining clinical and virological data in NHs increases understanding of transmission risks in this specific vulnerable population. PMID- 22091964 TI - Identification of genomic deletions spanning the PCDH19 gene in two unrelated girls with intellectual disability and seizures. AB - Recently, missense and truncating mutations in the gene PCDH19 have been reported to cause female-restricted epilepsy with mental retardation (EFMR). EFMR (MIM#300088) is an X-linked disorder characterized by early onset seizures and intellectual disability (ID). Interestingly, unlike typical X-linked mode of inheritance, the phenotype is restricted to females, and males are unaffected carriers. PCDH19 is highly expressed in brain, and the encoded protein belongs to the cadherin superfamily. Here we report two unrelated female patients with deletions spanning PCDH19 identified by copy number variation (CNV) analysis and validated by qPCR. In one, we have identified a 3 Mb interstitial deletion at Xq21.33-q22.1 which spans PCDH19, LOC442459 & TNMD. This patient had her first seizure at 8 months old, and also has ID and aggressive behavior. In another female patient we identified a de novo 603 kb heterozygous deletion in a female patient with fits (since 1 year of age), ID, hyperactivity and aggressive behavior. The deletion spans the entire PCDH19 gene (also TNMD, SRPX2, TSPAN6 and SYTL4). In conclusion, our results suggest that deletions at PCDH19 also cause EFMR. PMID- 22091965 TI - Streptomyces as symbionts: an emerging and widespread theme? AB - Streptomyces bacteria are ubiquitous in soil, conferring the characteristic earthy smell, and they have an important ecological role in the turnover of organic material. More recently, a new picture has begun to emerge in which streptomycetes are not in all cases simply free-living soil bacteria but have also evolved to live in symbiosis with plants, fungi and animals. Furthermore, much of the chemical diversity of secondary metabolites produced by Streptomyces species has most likely evolved as a direct result of their interactions with other organisms. Here we review what is currently known about the role of streptomycetes as symbionts with fungi, plants and animals. These interactions can be parasitic, as is the case for scab-causing streptomycetes, which infect plants, and the Streptomyces species Streptomyces somaliensis and Streptomyces sudanensis that infect humans. However, in most cases they are beneficial and growth promoting, as is the case with many insects, plants and marine animals that use streptomycete-produced antibiotics to protect themselves against infection. This is an exciting and newly emerging field of research that will become increasingly important as the search for new antibiotics switches to unusual and under-explored environments. PMID- 22091966 TI - Thoracic kyphosis associated with hemivertebra. AB - OBJECTIVE: To radiographically assess the influence of thoracic hemivertebra on kyphosis and neurologic status in 45 dogs. STUDY DESIGN: Case series. ANIMALS: French Bulldogs without neurologic signs (n = 41) and 4 dogs with compressive spinal cord disease associated with hemivertebra. METHODS: Thoracic spinal radiographs were divided into 3 groups: 1 = dogs with no hemivertebra, 2 = dogs with hemivertebra but no associated neurologic signs, and 3 = dogs with hemivertebra associated with clinical signs. Vertebral canal height, vertebral column angle, and the step between 2 adjacent vertebrae were measured in each group. RESULTS: Vertebral canal height was not significantly different in the 3 groups; however, mean vertebral column angle was significantly (P < .001) different between groups 1 (178 degrees ) and 2 (169 degrees ), and group 3 (133 degrees ). Median cranial step was significantly different between groups (P < .001): 0 mm (group 1), 0.3 mm (group 2), 3 mm (group 3). CONCLUSIONS: Vertebral canal height does not differ between normal dogs and dogs with thoracic hemivertebra. There is an important association between neurologic signs and kyphosis and subluxation. CLINICAL RELEVANCE: Vertebral realignment without vertebral canal opening could lead to spinal cord decompression in dogs affected by thoracic hemivertebra. PMID- 22091967 TI - Myosin regulatory light chain mutation found in hypertrophic cardiomyopathy patients increases isometric force production in transgenic mice. AB - FHC (familial hypertrophic cardiomyopathy) is a heritable form of cardiac hypertrophy caused by mutations in genes encoding sarcomeric proteins. The present study focuses on the A13T mutation in the human ventricular myosin RLC (regulatory light chain) that is associated with a rare FHC variant defined by mid-ventricular obstruction and septal hypertrophy. We generated heart-specific Tg (transgenic) mice with ~10% of human A13T-RLC mutant replacing the endogenous mouse cardiac RLC. Histopathological examinations of longitudinal heart sections from Tg-A13T mice showed enlarged interventricular septa and profound fibrotic lesions compared with Tg-WT (wild-type), expressing the human ventricular RLC, or non-Tg mice. Functional studies revealed an abnormal A13T mutation-induced increase in isometric force production, no change in the force-pCa relationship and a decreased Vmax of the acto-myosin ATPase. In addition, a fluorescence-based assay showed a 3-fold lower binding affinity of the recombinant A13T mutant for the RLC-depleted porcine myosin compared with WT-RLC. These results suggest that the A13T mutation triggers a hypertrophic response through changes in cardiac sarcomere organization and myosin cross-bridge function leading to abnormal remodelling of the heart. The significant functional changes observed, despite a low level of A13T mutant incorporation into myofilaments, suggest a 'poison peptide' mechanism of disease. PMID- 22091968 TI - Surface-modified solid lipid nanoparticulate formulation for ifosfamide: development and characterization. AB - AIMS: The present research focuses on the development of the surface modified solid lipid nanoparticulate (SLN) system for enhancing the stability and sustaining the release of a model hydrophilic drug ifosfamide. MATERIALS & METHODS: SLNs consisting of glyceryl monooleate (GMO) and chitosan were prepared by double emulsion technique, crosslinked with sodium tripolyphosphate, followed by lyophilization under two different vacuum conditions. The physicochemical characterization of SLNs included evaluation of surface morphology, particle size and surface charge, moisture content and physical state of the drug in the delivery system. The in vitro drug release and the stability were evaluated using high-performance liquid chromatography and liquid chromatography/mass spectrometry, respectively. Cellular permeability and subcellular localization studies were performed using Caco-2 cells. RESULTS: Different chamber pressures during lyophilization produced SLNs with different morphologies and moisture contents. SLNs demonstrated high encapsulation efficiency, sustained release, and enhanced stability of ifosfamide with a high cellular uptake and permeability for Caco-2 cells. CONCLUSION: GMO and chitosan SLNs could be successfully used for enhancing the stability, sustaining the release, enhancing the targeting and permeability characteristics of ifosfamide. PMID- 22091969 TI - Development of big five domains and facets in adulthood: mean-level age trends and broadly versus narrowly acting mechanisms. AB - Data from a cross-sectional sample (N = 601 men and women) and a longitudinal sample (N = 125 women) were used to test hypotheses about the development of Big Five domains and facets from early adulthood through middle age. Analyses of mean level age trends indicated that overall Agreeableness and Conscientiousness increased with age and that several facets showed distinctive trends that replicated across the samples. Cross-sectional analyses of trait intercorrelations and covariances indicated that interrelations between the Big Five domains, and between their more specific facets, were quite similar at older versus younger ages. Finally, longitudinal analyses of individual-level changes indicated that (a) different people's personalities changed in markedly different ways; (b) these changes were predominantly independent, rather than correlated, across Big Five domains; and (c) the pattern of change correlations between Big Five facets could be explained by the facets' interrelations at the first assessment time. Taken together, these results suggest that a complete understanding of personality development requires consideration of facet-level traits and that adult personality development is predominantly influenced by narrowly acting mechanisms that each affect a single Big Five domain, or a small cluster of related facets, rather than by broadly acting mechanisms that simultaneously affect previously independent traits. PMID- 22091970 TI - Application of a novel automatic disintegration apparatus for the development and evaluation of a direct compression rapidly disintegrating tablet. AB - An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab(r) concentration, DiPac(r)/Xylitab(r) ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability <10%) could be produced. The expansion coefficient (n) and the exponential rate constant (k) for disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab(r) and/or Xylitab(r), magnesium stearate, and Explotab(r) suggested that the amount of Explotab(r) was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel(r) and Explotab(r), which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone(r) XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol(r) showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena. PMID- 22091971 TI - Testosterone and sex hormone-binding globulin have significant association with metabolic syndrome in Taiwanese men. AB - OBJECTIVES: To investigate the relationship between sex hormones and metabolic syndrome (MS) in an Asian population. METHODS: A cross-sectional study was conducted in 237 men aged 20-88 years (mean age 52 years). Serum lipids, glucose, insulin, total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), and dehydroepiandosterone sulfate (DHEA-S) were measured along with body height, weight, waist circumference, and blood pressure. Free testosterone (FT) and bioavailable testosterone (BT) were calculated. Correlations were determined using univariate and multivariate regression analyses. RESULTS: Men with MS had lower levels of TT, BT, FT, SHBG and DHEA-S than men without MS. Multivariate analysis, after adjusting for age and smoking status, indicated that TT (OR: 0.909, 95% CI: 0.836-0.988, p = 0.003) and SHBG (OR: 0.948, 95% CI: 0.913-0.985, p = 0.006) were significantly associated with MS (R(2) = 0.314). TT was associated with waist circumference (p = 0.008) and abnormal triglycerides level (p = 0.006); SHBG was associated with blood pressure (p = 0.003), blood glucose (p = 0.043) and abnormal triglycerides (p = 0.048). A significant trend was observed between decreasing levels of TT, BT, FT, and SHBG and increasing numbers of MS components. CONCLUSION: Results show that serum testosterone and SHBG levels inversely correlate with MS in an Asian population applying the Asian MS definition. PMID- 22091972 TI - Comparison of computed tomography and myelography to a reference standard of computed tomographic myelography for evaluation of dogs with intervertebral disc disease. AB - OBJECTIVE: To compare the sensitivity of computed tomography (CT) and myelography to a reference standard of CT myelography for determining localization of Type I intervertebral disc extrusions in dogs. STUDY DESIGN: Prospective blinded comparative study. ANIMALS: Dogs with acute onset myelopathy because of suspected disc extrusions (n = 30). METHODS: Dogs had CT, myelography, and CT myelography to diagnose disc extrusions. Sensitivity of CT and myelography was compared to CT myelography for lateral, longitudinal, and combined localization. Confidence in the assessment of each imaging study was scored by 3 reviewers. RESULTS: Sensitivity of CT for lateral, longitudinal, and combined localization was 94%, 91%, and 81%, respectively, and was 64%, 74%, and 53%, respectively for myelography. Sensitivity of all 3 categories of localization was significantly different between modalities (P < .0001, P = .0031, P < .0001). Significant differences in the sensitivity of lateral and combined localization were found between confidence scores for myelography (P < .0001, P < .0001). Significant differences in the sensitivity of lateral, longitudinal, and combined localization were found between confidence scores for CT (P = .011, P = .013, P = .027). Poor sensitivity was obtained for both modalities except when imaging studies were assigned the highest confidence score. CONCLUSIONS: CT is a more sensitive imaging technique than myelography for localizing disc extrusions when compared to a reference standard of CT myelography. Both modalities yielded high sensitivity with the highest confidence score and poor sensitivity for all other confidence scores. PMID- 22091973 TI - Synthesis of azines in solid state: reactivity of solid hydrazine with aldehydes and ketones. AB - Highly conjugated azines were prepared by solid state grinding of solid hydrazine and carbonyl compounds such as aldehydes and ketones, using a mortar and a pestle. Complete conversion to the azine product is generally achieved at room temperature within 24 h, without using solvents or additives. The solid-state reactions afford azines as the sole products with greater than 97% yield, producing only water and carbon dioxide as waste. PMID- 22091974 TI - Reciprocal relationships between resource loss and psychological distress following exposure to political violence: an empirical investigation of COR theory's loss spirals. AB - We conducted a four-wave prospective study of Palestinian adults living in the West Bank, Gaza Strip, and East Jerusalem, interviewed between 2007 and 2009 at 6 month interval to explore transactional relationships between resource loss (i.e., intra and interpersonal resource loss) and psychological distress (i.e., posttraumatic stress disorder and depression symptoms). Initially, 1196 Palestinians completed the first wave interview and 752 of these participants completed all four interviews. A cross-lagged panel design was constructed to model the effects of trauma exposure on both resource loss and psychological distress and the subsequent reciprocal effects of resource loss and psychological distress across four time waves. Specifically, resource loss was modeled to predict distress, which in turn was expected to predict further resource loss. Structural equation modeling was used to test this design. We found that psychological distress significantly predicts resource loss across shorter, 6 month time waves, but that resource loss predicts distress across longer, 12 month intervals. These findings support the Conservation of Resources theory's corollary of loss spirals. PMID- 22091975 TI - Where did the ventricles go? PMID- 22091976 TI - Ethnic/race differences in the attrition of older American survey respondents: implications for health-related research. AB - OBJECTIVE: To compare models of attrition across race/ethnic groups of aging populations and discuss implications for health-related research. DATA SOURCES: The Health and Retirement Study (1992-2008). STUDY DESIGN: A competing risks model was estimated using a multinomial logit model when respondents faced competing types of risks, such as dying, being lost from the study, and nonresponse in some years for different groups of elderly. Key explanatory variables were foreign birth, health insurance, and health status. PRINCIPAL FINDINGS: Variables describing foreign birth, health insurance, and health status differed in their prediction of attrition across ethnic groups of aging populations. CONCLUSIONS: Differences in the predictors of attrition across ethnic groups of elderly could potentially lead to biased estimates in health related research using longitudinal data sources. PMID- 22091977 TI - Direct 1270 nm irradiation as an alternative to photosensitized generation of singlet oxygen to induce cell death. AB - This article is a highlight of the paper by Anquez et al. in this issue of Photochemistry and Photobiology and describes the potential benefits of direct excitation of molecular oxygen to produce singlet oxygen ((1)O(2)) rather than using a photosensitizer. Due to its simplicity, the direct excitation of molecular oxygen can potentially overcome problems associated with systemic administration of dyes, such as skin photosensitivity and the clearance of free sensitizer from the body. However, concerns associated with the technique include indiscriminate generation of extracellular and intracellular (1)O(2), the difficulty of controlling necrotic vs apoptotic cell death and the possible consequences of thermal effects. PMID- 22091978 TI - Different mental rotation strategies reflected in the rotation related negativity. AB - In a mental rotation task of objects, typically, reaction time (RT) increases and the rotation related negativity (RRN) increases in amplitude with increasing angles of rotation. However, in a mental rotation task of hands, different RT profiles can be observed for outward and inward rotated hands. In the present study, we examined the neurophysiological correlates of these asymmetries in the RT profiles. We used a mental rotation task with stimuli of left and right hands. In line with previous studies, the behavioral results showed a linear increase in RT for outward rotations, but not for inward rotations as a function of angular disparity. Importantly, the ERP results revealed an RRN for outward rotated stimuli, but not for inward rotated stimuli. This is the first study to show that the behaviorally observed differences in a mental rotation task of hands is also reflected at the neurophysiological level. PMID- 22091979 TI - Metabolic cost of daily activities and effect of mobility impairment in older adults. AB - OBJECTIVES: To compare metabolic equivalent (MET) values of common daily tasks in men and women aged 70 and older with normative criteria and to determine the effect of having mobility impairments. DESIGN: Cross-sectional observational study. SETTING: University-based research clinic. PARTICIPANTS: Forty-five participants aged 70 to 90 (mean 76.3 +/- 5.1) volunteered to complete 17 daily activities, each lasting 10 minutes. MEASUREMENTS: Oxygen consumption (VO(2) = mL/kg per minute) was measured through a mask using a portable gas analyzer, and MET values were calculated as measured VO(2) /3.5 mL/kg per minute. Values were compared with normative values and between participants with and without mobility impairments. RESULTS: Measured METs were different from the established normative criteria in 14 of 17 tasks performed. Normative values underestimated walking leisurely (0.87 +/- 0.12 METs) walking briskly (0.87 +/- 0.12 METs), and making beds (1.07 +/- 0.10 METs) but overestimated gardening (1.46 +/- 0.12 METs) and climbing stairs (0.73 +/- 0.18). Participants with impairments had significantly lower METs while gardening, vacuuming or sweeping, stair climbing, and walking briskly, although when METs were adjusted for performance speed, the metabolic costs were 16% to 27% higher for those with mobility impairments. CONCLUSION: Metabolic costs of daily activities are substantially different from normative values in older adults, and having mobility impairments increases this metabolic cost. These results may have implications for practitioners to appropriately prescribe daily physical activities for healthy and mobility-impaired older adults. PMID- 22091980 TI - How effective are short message service reminders at increasing clinic attendance? A meta-analysis and systematic review. AB - BACKGROUND AND OBJECTIVES: In the last few years there has been a steady uptake of mobile phone short message service (SMS) reminders to increase medical attendance rates. We undertook a review of studies that assessed the effectiveness of SMS reminders at increasing the uptake of appointments in health care settings. METHODS: We reviewed studies which involved a comparison of appointment attendance rates between patients who did and did not receive SMS reminders published prior to June 2010. We used meta-analysis methods to calculate the overall effect on attendance rates, stratified by study design and clinic type. RESULTS: The review criteria were met by 18 reports, made up of eight randomized controlled trials (RCTs) and 10 controlled observational studies. Across all studies, there was significant heterogeneity in the estimated effect measure of the relationship between use of SMS reminders and clinic attendance (I(2) = 90 percent; p < .01), so a summary effect estimate was not calculated. Stratification by study design showed that the heterogeneity was due to the observational studies. The summary effect from the RCTs was 1.48 (95% CI: 1.23-1.72) with no significant subgroup differences by clinic type (primary care clinics, hospital outpatient clinics), message timing (24, 48, and 72+ hours before the scheduled appointment), and target age group (pediatric, older). CONCLUSIONS: Short message service reminders in health care settings substantially increase the likelihood of attending clinic appointments. SMS reminders appear to be a simple and efficient option for health services to use to improve service delivery, as well as resulting in health benefits for the patients who receive the reminders. PMID- 22091984 TI - Electron-transfer studies with a new flavin adenine dinucleotide dependent glucose dehydrogenase and osmium polymers of different redox potentials. AB - A new extracellular flavin adenine dinucleotide (FAD)-dependent glucose dehydrogenase from Glomerella cingulata (GcGDH) was electrochemically studied as a recognition element in glucose biosensors. The redox enzyme was recombinantly produced in Pichia pastoris and homogeneously purified, and its glucose-oxidizing properties on spectrographic graphite electrodes were investigated. Six different Os polymers, the redox potentials of which ranged in a broad potential window between +15 and +489 mV versus the normal hydrogen electrode (NHE), were used to immobilize and "wire" GcGDH to the spectrographic graphite electrode's surface. The GcGDH/Os polymer modified electrodes were evaluated by chronoamperometry using flow injection analysis. The current response was investigated using a stepwisely increased applied potential. It was observed that the ratio of GcGDH/Os polymer and the overall loading of the enzyme electrode significantly affect the performance of the enzyme electrode for glucose oxidation. The best suited Os polymer [Os(4,4'-dimethyl-2,2'-bipyridine)(2)(PVI)Cl](+) had a potential of +309 mV versus NHE, and the optimum GcGDH/Os polymer ratio was 1:2 yielding a maximum current density of 493 MUA.cm(-2) at a 30 mM glucose concentration. PMID- 22091985 TI - Synthesis and characterization of (smif)2M(n) (n = 0, M = V, Cr, Mn, Fe, Co, Ni, Ru; n = +1, M = Cr, Mn, Co, Rh, Ir; smif =1,3-di-(2-pyridyl)-2-azaallyl). AB - A series of Werner complexes featuring the tridentate ligand smif, that is, 1,3 di-(2-pyridyl)-2-azaallyl, have been prepared. Syntheses of (smif)(2)M (1-M; M = Cr, Fe) were accomplished via treatment of M(NSiMe(3))(2)(THF)(n) (M = Cr, n = 2; Fe, n = 1) with 2 equiv of (smif)H (1,3-di-(2-pyridyl)-2-azapropene); ortho methylated ((o)Mesmif)(2)Fe (2-Fe) and ((o)Me(2)smif)(2)Fe (3-Fe) were similarly prepared. Metatheses of MX(2) variants with 2 equiv of Li(smif) or Na(smif) generated 1-M (M = Cr, Mn, Fe, Co, Ni, Zn, Ru). Metathesis of VCl(3)(THF)(3) with 2 Li(smif) with a reducing equiv of Na/Hg present afforded 1-V, while 2 Na(smif) and IrCl(3)(THF)(3) in the presence of NaBPh(4) gave [(smif)(2)Ir]BPh(4) (1(+) Ir). Electrochemical experiments led to the oxidation of 1-M (M = Cr, Mn, Co) by AgOTf to produce [(smif)(2)M]OTf (1(+)-M), and treatment of Rh(2)(O(2)CCF(3))(4) with 4 equiv Na(smif) and 2 AgOTf gave 1(+)-Rh. Characterizations by NMR, EPR, and UV-vis spectroscopies, SQUID magnetometry, X-ray crystallography, and DFT calculations are presented. Intraligand (IL) transitions derived from promotion of electrons from the unique CNC(nb) (nonbonding) orbitals of the smif backbone to ligand pi*-type orbitals are intense (epsilon ~ 10,000-60,000 M(-1)cm(-1)), dominate the UV-visible spectra, and give crystals a metallic-looking appearance. High energy K-edge spectroscopy was used to show that the smif in 1-Cr is redox noninnocent, and its electron configuration is best described as (smif(-))(smif(2 ))Cr(III); an unusual S = 1 EPR spectrum (X-band) was obtained for 1-Cr. PMID- 22091986 TI - Therapeutic hypothermia in adult cardiac arrest because of drowning. AB - BACKGROUND: Therapeutic hypothermia in adult victims who suffer cardiac arrest following drowning has been applied in only a small number of cases. In the last 4 years, we have employed therapeutic hypothermia to decrease hypoxia-induced brain injury in these patients. The purpose of the present study was to report the results of the treatment of these patients. METHODS: This study investigated the utilisation of therapeutic hypothermia on consecutive patients with cardiac arrest because of drowning between 2005 and 2008. The study was conducted retrospectively, collecting data by reviewing medical records. Hypothermia, with a target temperature of 32-34 degrees C, was induced for 24 h. Neurological outcomes were classified using the cerebral performance categories (CPCs). The primary outcome was neurological function at discharge. RESULTS: Twenty patients were treated with therapeutic hypothermia. Four patients (20%) exhibited a favourable neurological outcome (CPC 1-2). Two patients (10%) remained in a vegetative state at discharge (CPC 4), and 14 patients (70%) died (CPC 5). The most common complications during therapeutic hypothermia were pancreatitis and rhabdomyolysis. A longer duration of advanced cardiac life support (P = 0.035), an absence of motor response to pain after 3 days (P = 0.003), an abnormal brain imaging (P = 0.005) and a lack of cortical response to somatosensory evoked potential (P = 0.008) were related to an unfavourable outcome (CPC 3-5). CONCLUSION: The present study did not demonstrate an advantage of therapeutic hypothermia in adult cardiac arrest after drowning compared with previous studies treated with conventional therapy. Further prospective studies are needed to evaluate the effects of therapeutic hypothermia. PMID- 22091987 TI - The association between work stress and inflammatory biomarkers in Jordanian male workers. AB - The study aimed to establish the association of work stress, expressed as effort reward imbalance (ERI), and C-reactive protein (CRP) in 152 healthy Jordanian male employees. Self-report work stress, anthropometric data, and blood for CRP analysis were collected. A significant correlation between ERI and CRP (r = 0.29, p < .01), and between waist circumference with CRP (r = 0.44, p < .01) was found. Central obesity explained most of the variance in CRP after controlling for various covariates, and ERI was not a significant predictor of CRP (DeltaR2 = 0.02; beta = 0.15, p = .052). However, when only the centrally obese group was considered, ERI accounted for 5.0% of the variability in the CRP (beta = 0.24, p < .05). Results of this study confirm previous findings that obesity is significantly associated with CRP, and support the notion that higher ERI amongst obese workers is one small but significant predictor of increased levels of CRP. PMID- 22091988 TI - Enantiomeric interactions between liquid crystals and organized monolayers of tyrosine-containing dipeptides. AB - We have examined the orientational ordering of nematic liquid crystals (LCs) supported on organized monolayers of dipeptides with the goal of understanding how peptide-based interfaces encode intermolecular interactions that are amplified into supramolecular ordering. By characterizing the orientations of nematic LCs (4-cyano-4'-pentylbiphenyl and TL205 (a mixture of mesogens containing cyclohexane-fluorinated biphenyls and fluorinated terphenyls)) on monolayers of l-cysteine-l-tyrosine, l-cysteine-l-phenylalanine, or l-cysteine-l phosphotyrosine formed on crystallographically textured films of gold, we conclude that patterns of hydrogen bonds generated by the organized monolayers of dipeptides are transduced via macroscopic orientational ordering of the LCs. This conclusion is supported by the observation that the ordering exhibited by the achiral LCs is specific to the enantiomers used to form the dipeptide-based monolayers. The dominant role of the -OH group of tyrosine in dictating the patterns of hydrogen bonds that orient the LCs was also evidenced by the effects of phosphorylation of the tyrosine on the ordering of the LCs. Overall, these results reveal that crystallographic texturing of gold films can direct the formation of monolayers of dipeptides with long-range order, thus unmasking the influence of hydrogen bonding, chirality, and phosphorylation on the macroscopic orientational ordering of LCs supported on these surfaces. These results suggest new approaches based on supramolecular assembly for reporting the chemical functionality and stereochemistry of synthetic and biological peptide-based molecules displayed at surfaces. PMID- 22091989 TI - Binding of inositol stereoisomers to model amyloidogenic peptides. AB - The self-aggregation of proteins into amyloid fibrils is a pathological hallmark of numerous incurable diseases such as Alzheimer's disease. scyllo-Inositol is a stereochemistry-dependent in vitro inhibitor of amyloid formation. As the first step to elucidate its mechanism of action, we present molecular dynamics simulations of scyllo-inositol and its inactive stereoisomer, chiro-inositol, with simple peptide models, alanine dipeptide (ADP) and (Gly-Ala)(4). We characterize molecular interactions and compute equilibrium binding constants between inositol and ADP as well as, successively, monomers, amorphous aggregates, and fibril-like beta-sheet aggregates of (Gly-Ala)(4). Inositol interacts weakly with all peptide systems considered, with millimolar to molar affinities, and displaces the conformational equilibria of ADP but not of the (Gly-Ala)(4) systems. However, scyllo- and chiro-inositol adopt different binding modes on the surface of beta-sheet aggregates. These results suggest that inositol does not inhibit amyloid formation by breaking up preformed aggregates but rather by binding to the surface of prefibrillar aggregates. PMID- 22091990 TI - No role of homologous recombination in dealing with beta-lapachone cytotoxicity in yeast. AB - beta-Lapachone (beta-lap) is a promising antitumoral agent. DNA base oxidation and alkylation are among the expected damages by beta-lap. Herein, we have explored the role that the homologous recombination pathway (HR), a critical DNA repair process in Saccharomyces cerevisiae, has in the cytotoxic profile of beta lap. We have further compared beta-lap to the closely related compound menadione and the well-known alkylating agent methyl methanesulfonate (MMS). Surprisingly, we found that beta-lap does not trigger HR, as seen for (i) the mutant sensitivity profiles, (ii) concentration-dependent arrest profiles, (iii) absence of nuclear DNA repair factories, and (iv) frequency of recombination between direct repeats. PMID- 22091992 TI - Language concordance and patient-physician communication regarding mental health needs. AB - Language-related communication barriers between minority patients and their physicians may contribute to racial and ethnic disparities in mental health care. Accordingly, the current study sought to examine whether perceived mental health needs and discussion of these needs differed as a function of race or ethnicity and language concordance in older Latinos and Asian and Pacific Islanders (APIs). Using the 2007 California Health Interview Survey, the analytical sample included Latinos and APIs aged 55 and older (N = 2,960) who reported having seen a primary care provider within the past 2 years. Multivariable logistic regression was used to examine differences according to race or ethnicity and language concordance status (three groups: English-language concordant, other-language concordant, language discordant) in perceived mental health needs and discussion of those needs with a physician, adjusting for respondents' sociodemographic characteristics and mental health status. There were no significant differences in respondents' perceptions of their mental health needs across race or ethnicity or level of language concordance status (Ps > .41), although there were significant differences in whether respondents had discussed their mental health needs with their physicians according to participant race or ethnicity and language concordance status (adjusted odds ratio = 0.47, P = .04). Specifically, Spanish language-concordant Latinos were just as likely to discuss their mental health needs with their physicians as English language-concordant Latinos. In contrast, Asian language-concordant APIs were less likely to discuss their mental health needs with their physicians than English language-concordant APIs. There were no significant differences between language-discordant and English language concordant older adults in predicting discussion of mental health concerns. These findings underscore the importance of overcoming language-related and cultural barriers to improve patient-provider discussions of older adults' mental health needs. PMID- 22091993 TI - Comparison of transvaginal natural orifice transluminal endoscopic surgery (NOTES(r)) and laparoscopy for elective bilateral ovariectomy in standing mares. AB - OBJECTIVE: To compare surgical trauma, perioperative pain, surgical time, and complication rate in mares undergoing standing bilateral ovariectomy by natural orifice transluminal endoscopic surgery (NOTES) or laparoscopy. STUDY DESIGN: Experimental study. ANIMALS: Healthy mares (n = 12). METHODS: Ovariectomy was performed with a vessel-sealing device by transvaginal NOTES (n = 6) using a flexible endoscope and specialized instruments or by bilateral flank laparoscopy (n = 6). Preoperative and postoperative complete blood count (CBC), plasma fibrinogen concentration, serum amyloid A concentration, peritoneal nucleated cell count, and total protein concentration were compared using repeated measures ANOVA. Surgical times were compared using an unpaired t-test. Mares were monitored for 2 weeks postoperatively and necropsy was performed at 3 weeks (n = 6) or 3 months (n = 6) to assess short- and medium-term effects of each procedure. Complication rate, necropsy, and bacteriology findings were compared using a Fishers exact test. Significance was set at P < .05. RESULTS: All surgical procedures were performed successfully and all but one laparoscopy mare were bright, alert, and maintained a good appetite until euthanasia. Mean +/- SD surgical time was similar between groups (NOTES: 100 +/- 40 minutes; laparoscopy: 107 +/- 47 minutes). There were no significant temporal differences in vital parameters, CBC, plasma fibrinogen concentration, serum amyloid A concentration, peritoneal nucleated cell count, and total protein concentration between groups. CONCLUSIONS: Bilateral ovariectomy by transvaginal NOTES or laparoscopy resulted in minimal inflammation and surgical trauma. PMID- 22091994 TI - Seasonalizing mountain system recharge in semi-arid basins-climate change impacts. AB - Climate variability and change impact groundwater resources by altering recharge rates. In semi-arid Basin and Range systems, this impact is likely to be most pronounced in mountain system recharge (MSR), a process which constitutes a significant component of recharge in these basins. Despite its importance, the physical processes that control MSR have not been fully investigated because of limited observations and the complexity of recharge processes in mountainous catchments. As a result, empirical equations, that provide a basin-wide estimate of mean annual recharge using mean annual precipitation, are often used to estimate MSR. Here North American Regional Reanalysis data are used to develop seasonal recharge estimates using ratios of seasonal (winter vs. summer) precipitation to seasonal actual or potential evapotranspiration. These seasonal recharge estimates compared favorably to seasonal MSR estimates using the fraction of winter vs. summer recharge determined from isotopic data in the Upper San Pedro River Basin, Arizona. Development of hydrologically based seasonal ratios enhanced seasonal recharge predictions and notably allows evaluation of MSR response to changes in seasonal precipitation and temperature because of climate variability and change using Global Climate Model (GCM) climate projections. Results show that prospective variability in MSR depends on GCM precipitation predictions and on higher temperature. Lower seasonal MSR rates projected for 2050-2099 are associated with decreases in summer precipitation and increases in winter temperature. Uncertainty in seasonal MSR predictions arises from the potential evapotranspiration estimation method, the GCM downscaling technique and the exclusion of snowmelt processes. PMID- 22091995 TI - E-genetics: exploring the acceptability and feasibility of using technology in cancer genetics services. AB - The use of information and communication technologies (ICTs) in the delivery of cancer genetics services could improve equality of access in rural areas and help meet the increasing demand for specialist genetics services. An online patient survey and focus groups with patients and staff from the Cancer Genetics Service for Wales (CGSW) were used to explore the acceptability and feasibility of utilizing ICTs within genetics services, which we have termed e-genetics. A total of 225 patients completed the online survey. Many aspects of e-genetics proposed in the survey were highly acceptable to patients, including an electronic version of the family history questionnaire, an email facility for cancer genetic queries, and a computerized decision-aid. Participants in the focus groups emphasized the importance of patient choice when developing new models of service delivery. For example, the use of genetic counselling via telemedicine was not considered to be preferable to face-to-face clinic appointments but could benefit those unable to travel. This article highlights the fact that e-genetics initiatives may not be appropriate for all cancer genetics service users. However, user-friendly developments that can be easily implemented and attend to individual needs could improve efficiency and cost-effectiveness, whilst providing high-quality services to remote areas. PMID- 22091996 TI - To discover or to create: metaphors and the true self. AB - Three studies examined how endorsement of self-discovery and self-creation metaphors influences belief in the true self and its use as meaning source. It was hypothesized that discovery metaphors contribute to belief in the true self and bolster the relationship between true self-knowledge and meaning. Study 1 supported the hypothesis that discovery is positively associated with belief in the true self among a sample of college students (N = 311). Studies 2 and 3 extended the analysis by showing that the discovery metaphor also facilitates perceptions of meaning and the use of the true self specifically as a source of meaning in a second sample of college students (N = 75) as well as an adult sample of university employees (N = 173). Implications for understanding what enables the true self to infuse life with meaning, as well as an individual differences approach to metaphoric cognition, are discussed. PMID- 22091997 TI - Impact of phosphoproteomics on studies of bacterial physiology. AB - Protein phosphorylation on serine, threonine and tyrosine is recognized as a major tool of signal transduction in bacteria. However, progress in the field has been hampered by the lack of global and site-specific data on bacterial phosphoproteomes. Recent advances in mass spectrometry-based proteomics have encouraged bacteriologists to start using powerful gel-free approaches for global detection of phosphorylated proteins. These studies have generated large data sets of proteins phosphorylated on serine, threonine and tyrosine, with identified phosphorylation sites which represent an excellent starting point for in-depth physiological characterization of kinases and their substrates. The list of phosphorylated proteins inspired a number of physiological studies in which the identity of the phosphorylation site facilitated the elucidation of molecular mechanisms of signaling and regulation. Bacterial phosphoproteomics also provided interesting insights into the evolutionary aspects of protein phosphorylation. The field is rapidly embracing quantitative mass spectrometry strategies, comparing phosphoproteome dynamics in changing conditions and aiming to reconstruct the entire regulatory networks by linking kinases to their physiological substrates. PMID- 22091998 TI - Oxidation of Met1606 in von Willebrand factor is a risk factor for thrombotic and septic complications in chronic renal failure. AB - CKD (chronic kidney disease) is a life-threatening pathology, often requiring HD (haemodialysis) and characterized by high OS (oxidative stress), inflammation and perturbation of vascular endothelium. HD patients have increased levels of vWF (von Willebrand factor), a large protein (~240 kDa) released as UL-vWF (ultra large-vWF polymers, molecular mass ~20000-50000 kDa) from vascular endothelial cells and megakaryocytes, and responsible for the initiation of primary haemostasis. The pro-haemostatic potential of vWF increases with its length, which is proteolytically regulated by ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), a zinc-protease cleaving vWF at the single Tyr1605-Met1606 bond, and by LSPs (leucocyte serine proteases), released by activated PMNs (polymorphonuclear cells) during bacterial infections. Previous studies have shown that in vitro oxidation of Met1606 hinders vWF cleavage by ADAMTS-13, resulting in the accumulation of UL-vWF that are not only more pro-thrombotic than shorter vWF oligomers, but also more efficient in binding to bacterial adhesins during sepsis. Notably, HD patients have increased risk of developing dramatic cardiovascular and septic complications, whose underlying mechanisms are largely unknown. In the present study, we first purified vWF from HD patients and then chemically characterized its oxidative state. Interestingly, HD-vWF contains high carbonyl levels and increased proportion of UL-vWF polymers that are also more resistant to ADAMTS-13. Using TMS (targeted MS) techniques, we estimated that HD-vWF contains >10% of Met1606 in the sulfoxide form. We conclude that oxidation of Met1606, impairing ADAMTS-13 cleavage, results in the accumulation of UL-vWF polymers, which recruit and activate platelets more efficiently and bind more tightly to bacterial adhesins, thus contributing to the development of thrombotic and septic complications in CKD. PMID- 22091999 TI - Identification of two novel coccidian species shed by California sea lions (Zalophus californianus). AB - Routine fecal examination revealed novel coccidian oocysts in asymptomatic California sea lions (Zalophus californianus) in a rehabilitation facility. Coccidian oocysts were observed in fecal samples collected from 15 of 410 California sea lions admitted to The Marine Mammal Center between April 2007 and October 2009. Phylogenetic analysis using the full ITS-1 region, partial small subunit 18S rDNA sequence, and the Apicomplexa rpoB region identified 2 distinct sequence clades, referred to as Coccidia A and Coccidia B, and placed them in the Sarcocystidae, grouped with the tissue-cyst-forming coccidia. Both sequence clades resolved as individual taxa at ITS-1 and rpoB and were most closely related to Neospora caninum. Coccidia A was identified in 11 and Coccidia B in 4 of 12 sea lion oocyst samples successfully sequenced (3 of those sea lions were co-infected with both parasites). Shedding of Coccidia A oocysts was not associated with age class, sex, or stranding location, but yearlings represented the majority of shedders (8/15). This is the first study to use molecular phylogenetics to identify and describe coccidian parasites shed by a marine mammal. PMID- 22092000 TI - Enantioselective bromocyclization of olefins catalyzed by chiral phosphoric acid. AB - A chiral phosphoric acid catalyzed enantioselective bromocyclization of olefins is described. Various cis-, trans-, or trisubstituted gamma-hydroxy-alkenes and gamma-amino-alkenes can cyclize under the reaction conditions to give optically active 2-substituted tetrahydrofurans and tetrahydropyrroles in up to 91% ee. PMID- 22092002 TI - Insulin pump therapy for pregnancy: a primer. AB - Current knowledge and advances in insulin formulations, insulin pump technology, and blood glucose monitoring techniques have improved practitioners' ability to achieve diabetic people's blood glucose targets. Practitioners and pregnant women should bear in mind that important differences exist in glucose metabolism during pregnancy and require a different approach from non-pregnant people to avoid pregnant women's experience being adversely affected. Insulin pump therapy, if used skillfully by practitioners and their pregnant patients, can be especially beneficial for some diabetic women during their pregnancies. Women's healthcare practitioners should endeavor to be familiar with this therapy, even if they are not experts in its full complexity. PMID- 22092001 TI - Molecular heterogeneity in the choroid plexus epithelium: the 22-member gamma protocadherin family is differentially expressed, apically localized, and implicated in CSF regulation. AB - The choroid plexus (CP) epithelium develops from the ependyma that lines the ventricular system, and plays a critical role in the development and function of the brain. In addition to being the primary site of CSF production, the CP maintains the blood-CSF barrier via apical tight junctions between epithelial cells. Here we show that the 22-member gamma-protocadherin (gamma-Pcdh) family of cell adhesion molecules, which we have implicated previously in synaptogenesis and neuronal survival, is highly expressed by both CP epithelial and ependymal cells, in which gamma-Pcdh protein localization is, surprisingly, tightly restricted to the apical membrane. Multi-label immunostaining demonstrates that gamma-Pcdhs are excluded from tight junctions, basolateral adherens junctions, and apical cilia tufts. RT-PCR analysis indicates that, as a whole, the CP expresses most members of the Pcdh-gamma gene family. Immunostaining using novel monoclonal antibodies specific for single gamma-Pcdh proteins shows that individual epithelial cells differ in their apically localized gamma-Pcdh repertoire. Restricted mutation of the Pcdh-gamma locus in the choroid plexus and ependyma leads to significant reductions in ventricular volume, without obvious disruptions of epithelial apical-basal polarity. Together, these results suggest an unsuspected role for the gamma-Pcdhs in CSF production and demonstrate a surprising molecular heterogeneity in the CP epithelium. PMID- 22092003 TI - From goal motivation to goal progress: the mediating role of coping in the Self Concordance Model. AB - The present studies examined the mediating role of self-regulatory mechanisms in the relationship between goal motivation and goal progress in the Self Concordance Model. First, a systematic review, using meta-analytical path analysis, supported the mediating role of effort and action planning in the positive association between autonomous goal motivation and goal progress. Second, results from two additional empirical studies, using structural equation modeling, lent credence to the mediating role of coping in the relationship between goal motivation and goal progress of university students. Autonomous goal motivation was positively associated with task-oriented coping, which predicted greater goal progress during midterm exams (Study 1, N=702) and at the end of the semester in a different sample (Study 2, N=167). Controlled goal motivation was associated with greater disengagement-oriented coping (Study 1 and Study 2) and lesser use of task-oriented coping (Study 2), which reduced goal progress. These results held up after controlling for perceived stress (Study 2). Our findings highlight the importance of coping in the "inception-to-attainment" goal process because autonomous goal motivation indirectly rather than directly predicts goal progress of university students through their usage of task-oriented coping. PMID- 22092004 TI - Health care reform in the former Soviet Union: beyond the transition. AB - OBJECTIVE: To assess accessibility and affordability of health care in eight countries of the former Soviet Union. DATA SOURCES/STUDY SETTING: Primary data collection conducted in 2010 in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Moldova, Russia, and Ukraine. STUDY DESIGN: Cross-sectional household survey using multistage stratified random sampling. DATA COLLECTION/EXTRACTION METHODS: Data were collected using standardized questionnaires with subjects aged 18+ on demographic, socioeconomic, and health care access characteristics. Descriptive and multivariate regression analyses were used. PRINCIPAL FINDINGS: Almost half of respondents who had a health problem in the previous month which they viewed as needing care had not sought care. Respondents significantly less likely to seek care included those living in Armenia, Georgia, or Ukraine, in rural areas, aged 35-49, with a poor household economic situation, and high alcohol consumption. Cost was most often cited as the reason for not seeking health care. Most respondents who did obtain care made out-of-pocket payments, with median amounts varying from $13 in Belarus to $100 in Azerbaijan. CONCLUSIONS: Access to health care and within-country inequalities appear to have improved over the past decade. However, considerable problems remain, including out-of-pocket payments and unaffordability despite efforts to improve financial protection. PMID- 22092005 TI - Pharmacokinetic analysis and optimization of hydroxycamptothecin-loaded nanoparticles for liver targeting. AB - In this paper, a pharmacokinetic model to describe the tissue distribution process of nanoparticles was established. To test the possibility of the model, nanoparticles composed of poly(butylcyanoacrylate) and hydroxypropyl-beta cyclodextrins (HP-beta-CD) was prepared with a poorly soluble anticancer drug, hydroxycamptothecin (HCPT). Characteristics were determined including particle's size, morphology and in vitro release. The tissue distribution of nanoparticles was also studied. Further, mathematical equation was fitted to the curve of drug concentration-time in liver of hydroxycamptothecin-loaded nanoparticles and the pharmacokinetic parameters of liver were obtained. The effectiveness of hydroxycamptothecin-loaded nanoparticles for liver targeting was evaluated. The results showed that nanoparticles composed of poly(butylcyanoacrylate) and hydroxypropyl-beta-cyclodextrins (HP-beta-CD) exhibited enhanced liver targeting in rats after i.v. injection. More importantly, the pharmacokinetic parameters (transport constant from blood to target organ KT, drug release rate from nanoparticles Kr and drug elimination constant in target organ Ke) provided some quantitative measure of liver distribution and were useful guidelines for development of targeted drug delivery systems. PMID- 22092006 TI - The effects of marital status on episodic and semantic memory in healthy middle aged and old individuals. AB - The present study examined the influences of marital status on different episodic and semantic memory tasks. A total of 1882 adult men and women participated in a longitudinal project (Betula) on memory, health and aging. The participants were grouped into two age cohorts, 35-60 and 65-85, and studied over a period of 5 years. Episodic memory tasks concerned recognition and recall, whereas semantic memory tasks concerned knowledge and fluency. The results showed, after controlling for education, some diseases, chronological age and leisure activity as covariates, that there were significant differences between married and single individuals in episodic memory, but not in semantic memory. Married people showed significantly better memory performances than singles in both subsystems of episodic memory, that is, recall and recognition. Also, the rate of decline in episodic memory was significantly larger for singles and widowed than other groups over the 5-year time period in both age groups. The findings demonstrate that the positive relation found between marriage and health can be extended to the relation between marriage and cognitive performance. This effect might be explained by the role played by cognitive stimulation in memory and cognition. PMID- 22092007 TI - The consistency between treatments provided to nursing facility residents and orders on the physician orders for life-sustaining treatment form. AB - OBJECTIVES: To evaluate the consistency between treatments provided and Physician Orders for Life-Sustaining Treatment (POLST) orders. DESIGN: Retrospective chart abstraction. SETTING: Stratified, random sample of 90 nursing facilities in Oregon, Wisconsin, and West Virginia. PARTICIPANTS: Eight hundred seventy living and deceased nursing facility residents aged 65 and older with a minimum 60-day stay. MEASUREMENTS: Chart data about POLST form orders and related treatments over a 60-day period were abstracted. Decision rules were created to determine whether the rationale for each treatment was consistent with POLST orders. RESULTS: Most residents (85.2%) had the same POLST form in place during the review period. A majority of treatments provided to residents with orders for comfort measures only (74.3%) and limited antibiotics (83.3%) were consistent with POLST orders because they were primarily comfort focused rather than life prolonging, but antibiotics were provided to 32.1% of residents with orders for no antibiotics. Overall consistency rates between treatments and POLST orders were high for resuscitation (98%), medical interventions (91.1%), and antibiotics (92.9%) and modest for feeding tubes (63.6%). In all, POLST orders were consistent with treatments provided 94.0% of the time. CONCLUSION: With the exception of feeding tubes and antibiotic use in residents with orders for no antibiotics, the use of medical treatments was nearly always consistent with POLST orders to provide or withhold life-sustaining interventions. The POLST program is a useful tool for ensuring that the treatment preferences of nursing facility residents are honored. PMID- 22092008 TI - Designer drugs: a medicinal chemistry perspective. AB - There are numerous medicinal chemistry reports in the literature describing the pharmacological properties of thousands of narcotics, stimulants, hallucinogens, sedative-hypnotic drugs, cannabinoids, and other psychoactive substances as well as synthetic methods for their preparations. This information, while essential for the advancement of science, has been used by clandestine chemists to manufacture and market an endless variety of analogs of so-called designer drugs. In this review, we describe how clandestine chemists used the principles of medicinal chemistry to design molecules, referred to as designer drugs, that elicit the effects of opioids, amphetamine and analogs, cannabinoids, and phencyclidine analogs while circumventing the law. PMID- 22092009 TI - The productivity and cost-efficiency of models for involving nurse practitioners in primary care: a perspective from queueing analysis. AB - OBJECTIVE: To develop simple stylized models for evaluating the productivity and cost-efficiencies of different practice models to involve nurse practitioners (NPs) in primary care, and in particular to generate insights on what affects the performance of these models and how. DATA SOURCES AND STUDY DESIGN: The productivity of a practice model is defined as the maximum number of patients that can be accounted for by the model under a given timeliness-to-care requirement; cost-efficiency is measured by the corresponding annual cost per patient in that model. Appropriate queueing analysis is conducted to generate formulas and values for these two performance measures. Model parameters for the analysis are extracted from the previous literature and survey reports. Sensitivity analysis is conducted to investigate the model performance under different scenarios and to verify the robustness of findings. PRINCIPAL FINDINGS: Employing an NP, whose salary is usually lower than a primary care physician, may not be cost-efficient, in particular when the NP's capacity is underutilized. Besides provider service rates, workload allocation among providers is one of the most important determinants for the cost-efficiency of a practice model involving NPs. Capacity pooling among providers could be a helpful strategy to improve efficiency in care delivery. CONCLUSIONS: The productivity and cost-efficiency of a practice model depend heavily on how providers organize their work and a variety of other factors related to the practice environment. Queueing theory provides useful tools to take into account these factors in making strategic decisions on staffing and panel size selection for a practice model. PMID- 22092010 TI - Pyridazine based scorpionate ligand in a copper boratrane compound. AB - Reaction of potassium tris(mercapto-tert-butylpyridazinyl)borate K[Tn(tBu)] with copper(II) chloride in dichloromethane at room temperature led to the diamagnetic copper boratrane compound [Cu{B(Pn(tBu))(3)}Cl] (Pn = pyridazine-3-thionyl) (1) under activation of the B-H bond and formation of a Cu-B dative bond. In contrast to this, stirring of the same ligand with copper(I) chloride in tetrahydrofuran (THF) gave the dimeric compound [Cu{Tn(tBu)}](2) (2) where one copper atom is coordinated by two sulfur atoms and one hydrogen atom of one ligand and one sulfur of the other ligand. Hereby, no activation of the B-H bond occurred but a 3-center-2-electron B-H...Cu bond is formed. The reaction of copper(II) chloride with K[Tn(tBu)] in water gave the same product 2, but a formal reduction of the metal center from Cu(II) to Cu(I) occurred. When adding tricyclohexyl phosphine to the reaction mixture of K[Tn(R)] (R = tBu, Me) and copper(I) chloride in MeOH, the distorted tetrahedral Cu complexes [Cu{Tn(R)}(PCy(3))] (R = tBu 3, Me 4) were formed. Compound 4 is exhibiting an "inverted" kappa(3)-H,S,S, coordination mode. The copper boratrane 1 was further investigated by density functional theory (DFT) calculations for a better understanding of the M->B interaction involving the d(8) electron configuration of Cu. PMID- 22092011 TI - Exploring priorities for public health genomics. PMID- 22092012 TI - Transcranial Doppler microembolic signals and serum marker evidence of brain injury during transcatheter aortic valve implantation. AB - BACKGROUND: Recent studies have shown that transcatheter aortic valve implantation (TAVI) is associated with new foci of restricted diffusion on cerebral magnetic resonance imaging suggestive of cerebral microembolism. The aim of the present investigation was to quantify the cerebral embolic load and to evaluate during which phase of the TAVI procedure microembolism occurs. We also evaluated the association between the cerebral embolic load and post-procedural release of S100B, a serological marker of cerebral injury. METHODS: In 21 patients, we described the extent and intra-procedural distribution of microemboli during the TAVI procedure using the transcranial Doppler technique. S100B, a marker of astroglial injury, was measured for 24 h after the procedure, and the area under the curve (AUC(24h) ) relating S100B to time was calculated. RESULTS: During the TAVI procedure, a mean of 282 +/- 169 emboli was detected, 37% occurred during manipulation of the aortic arch/root/valve by guide wires and catheters, 22% occurred immediately after balloon dilatation of the native valve and 41% occurred during frame expansion of the valve prosthesis. S100B increased in all patients with a peak at 1 h after the procedure and returned to baseline after 4 h. There was a positive correlation between the total amount of cerebral microemboli and the AUC(24h) for S100B (r = 0.68, P < 0.001). None of the patients developed neurological impairment. CONCLUSION: TAVI is associated with a substantial amount of cerebral microemboli. The microembolic load correlates to the degree of post-procedural release of a marker of cerebral injury. PMID- 22092013 TI - Theoretical evaluation of structural models of the S2 state in the oxygen evolving complex of Photosystem II: protonation states and magnetic interactions. AB - Protonation states of water ligands and oxo bridges are intimately involved in tuning the electronic structures and oxidation potentials of the oxygen evolving complex (OEC) in Photosystem II, steering the mechanistic pathway, which involves at least five redox state intermediates S(n) (n = 0-4) resulting in the oxidation of water to molecular oxygen. Although protons are practically invisible in protein crystallography, their effects on the electronic structure and magnetic properties of metal active sites can be probed using spectroscopy. With the twin purpose of aiding the interpretation of the complex electron paramagnetic resonance (EPR) spectroscopic data of the OEC and of improving the view of the cluster at the atomic level, a complete set of protonation configurations for the S(2) state of the OEC were investigated, and their distinctive effects on magnetic properties of the cluster were evaluated. The most recent X-ray structure of Photosystem II at 1.9 A resolution was used and refined to obtain the optimum structure for the Mn(4)O(5)Ca core within the protein pocket. Employing this model, a set of 26 structures was constructed that tested various protonation scenarios of the water ligands and oxo bridges. Our results suggest that one of the two water molecules that are proposed to coordinate the outer Mn ion (Mn(A)) of the cluster is deprotonated in the S(2) state, as this leads to optimal experimental agreement, reproducing the correct ground state spin multiplicity (S = 1/2), spin expectation values, and EXAFS-derived metal-metal distances. Deprotonation of Ca(2+)-bound water molecules is strongly disfavored in the S(2) state, but dissociation of one of the two water ligands appears to be facile. The computed isotropic hyperfine couplings presented here allow distinctions between models to be made and call into question the assumption that the largest coupling is always attributable to Mn(III). The present results impose limits for the total charge and the proton configuration of the OEC in the S(2) state, with implications for the cascade of events in the Kok cycle and for the water splitting mechanism. PMID- 22092014 TI - Determinants of death in the hospital among older adults. AB - OBJECTIVES: To investigate patient-level determinants of in-hospital death, adjusting for patient and regional characteristics. DESIGN: Using multivariable regression, the relationship between in-hospital death and participants' social, functional, and health characteristics was investigated, controlling for regional Hospital Care Intensity Index (HCI) from the Dartmouth Atlas of Health Care. SETTING: The Health and Retirement Study, a longitudinal nationally representative cohort of older adults. PARTICIPANTS: People aged 67 and older who died between 2,000 and 2,006 (N = 3,539) were sampled. MEASUREMENTS: In-hospital death. RESULTS: Thirty-nine percent (n = 1,380) of participants died in the hospital (range 34% in Midwest to 45% in Northeast). Nursing home residence, functional dependence, and cancer or dementia diagnosis, among other characteristics, were associated with lower adjusted odds of in-hospital death. Being black or Hispanic, living alone, and having more medical comorbidities were associated with greater adjusted odds, as was higher HCI. Sex, education, net worth, and completion of an advance directive did not correlate with in-hospital death. CONCLUSION: Black race, Hispanic ethnicity, and other functional and social characteristics are correlates of in-hospital death, even after controlling for the role of HCI. Further work must be done to determine whether preferences, provider characteristics and practice patterns, or differential access to medical and community services drive this difference. PMID- 22092015 TI - Contrast of the biological activity of negatively and positively charged microwave synthesized CdSe/ZnS quantum dots. AB - Quantum dots (QDs) are semiconductor nanocrystals that have found use in bioimaging, cell tracking, and drug delivery. This article compares the cytotoxicity and cellular interactions of positively and negatively charged CdSe/CdS/ZnS QDs prepared by a microwave method using a murine alveolar macrophage-like cell culture model. Keeping the core semiconductor the same, QD charge was varied by altering the surface capping molecule; negatively charged QDs were formed with mercaptopropionic acid (MPA-QDs) and positively charged QDs with thiocholine (THIO-QDs). The size and charge of these two QDs were investigated in three types of media (RPMI, RPMI + FBS, and X-VIVO serum-free media) relevant for the biological studies. MPA-QDs were found to have negative zeta potential in RPMI, RPMI + FBS, and serum-free media and had sizes ranging from 8 to 54 nm. THIO-QDs suspended in RPMI alone were <62 nm in size, while large aggregates (greater than 1000 nm) formed when these QDs were suspended in RPMI + FBS and serum-free media. THIO-QDs retained positive zeta potential in RPMI and were found to have a negative zeta potential in RPMI + FBS and nearly neutral zeta potential in serum-free media. In a cell culture model, both MPA-QDs and THIO-QDs caused comparable levels of apoptosis and necrosis. Both QDs induced significant tumor necrosis factor-alpha (TNF-alpha) secretion only at high concentrations (>250 nM). Both types of QDs were internalized via clathrin dependent endocytosis. Using real-time, live cell imaging, we found that MPA-QDs interact with the cell surface within minutes and progress through the endocytic pathway to the lysosomes upon internalization. With the THIO-QDs, the internalization process was slower, but the pathways could not be mapped because of spectroscopic interference caused by QD aggregates. Finally, MPA-QDs were found to associate with cell surface scavenger receptors, while the THIO-QDs did not. This study indicates that the surface charge and aggregation characteristics of QDs change drastically in biological culture conditions and, in turn, influence nanoparticle and cellular interactions. PMID- 22092017 TI - The nursing hypothesis: an evolutionary account of emotional modulation of the postauricular reflex. AB - The postauricular reflex (PAR) is anomalous because it seems to be potentiated during positive emotions and inhibited during negative states, unlike eyeblink and other components of the startle reflex. Two evolutionary explanations based on simian facial emotion expressions were tested. Reflexes were elicited while 47 young adult volunteers made lip pursing or grimacing poses and viewed neutral, intimidating, or appetitive photos. The PAR was enhanced during appetitive slides, but only as subjects carried out the lip-pursing maneuver. These results support the nursing hypothesis, which assumes that infant mammals instinctively retract their pinnae while nursing in order to comfortably position the head. Appetitive emotions prime the ear-retraction musculature, even in higher primates whose postauricular muscles are vestigial. PMID- 22092018 TI - Merged- and separate-band behavior of the C?O stretching band in N,N dimethylformamide isotopic liquid mixtures: DMF/DMF-d1, DMF/DMF-d6, and DMF/DMF 13C?O. AB - A combined experimental and theoretical analysis is carried out on the polarized (isotropic and anisotropic) Raman spectra in the spectral region of the C?O stretching (amide I) band of three isotopic liquid mixtures of N,N dimethylformamide (normal/d(1), normal/d(6), and normal/(13)C?O). Two distinct types of spectral behavior are found for the isotropic Raman spectra: the separate-band behavior (for normal/(13)C?O), where two separate bands (one for each species) appear at all concentrations but with significant intensity bias, and the merged-band behavior (for normal/d(6)), where only one band appears at a frequency between those of the two species and with a band shape noticeably different from the simple overlap of their profiles. An intermediate case between these two limits is also found (for normal/d(1)). These main spectral features, as well as the noncoincidence effect (NCE) observed for all the mixtures and neat liquids, are well reproduced by the calculations, meaning that (1) the computational procedure (carried out in the time domain) incorporates all the important factors that determine the main spectral features, and (2) the band merger and the intensity bias are both controlled by the same type of term (resonant intermolecular vibrational coupling) of the vibrational Hamiltonian that gives rise to the NCE. Based on this result, the one- and two-dimensional infrared spectra of the normal/d(1) 1:1 mixture are calculated as theoretical predictions. For this purpose, an eigenstate-free method is developed to increase the efficiency of the time-domain spectral calculations and to do the calculations on a largest possible system. The calculated spectral features are compared with those of the polarized Raman spectra and discussed. PMID- 22092019 TI - Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle. AB - X-linked dilated cardiomyopathy is a pure cardiac dystrophinopathy phenotype mainly caused by DMD mutations that present a specific transcription effect in cardiac tissue. We report a 26-year-old male who presented with severe dilated cardiomyopathy and high creatine kinase. The patient did not complain of skeletal muscle weakness. A muscle biopsy showed mild dystrophic changes and a low proportion of dystrophin-negative fibres. A molecular study identified a nonsense DMD mutation (p.Arg2098X) in somatic mosaicism. The ratio of mutant versus normal allele in blood and skeletal muscle suggests selective pressure against mutant muscle cells, a process known as genetic normalization. We hypothesize that this process may have mitigated skeletal muscle symptoms in this patient. This is the second report of a DMD somatic mosaic with evidence of genetic normalization in muscle. Somatic DMD mutations should be considered in patients presenting with idiopathic dilated cardiomyopathy. PMID- 22092020 TI - Why physicians should like bundled payment. PMID- 22092021 TI - Examining multiple sources of differential item functioning on the Clinician & Group CAHPS(r) survey. AB - OBJECTIVE: To evaluate psychometric properties of a widely used patient experience survey. DATA SOURCES: English-language responses to the Clinician & Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS(r)) survey (n = 12,244) from a 2008 quality improvement initiative involving eight southern California medical groups. METHODS: We used an iterative hybrid ordinal logistic regression/item response theory differential item functioning (DIF) algorithm to identify items with DIF related to patient sociodemographic characteristics, duration of the physician-patient relationship, number of physician visits, and self-rated physical and mental health. We accounted for all sources of DIF and determined its cumulative impact. PRINCIPAL FINDINGS: The upper end of the CG-CAHPS(r) performance range is measured with low precision. With sensitive settings, some items were found to have DIF. However, overall DIF impact was negligible, as 0.14 percent of participants had salient DIF impact. Latinos who spoke predominantly English at home had the highest prevalence of salient DIF impact at 0.26 percent. CONCLUSIONS: The CG-CAHPS(r) functions similarly across commercially insured respondents from diverse backgrounds. Consequently, previously documented racial and ethnic group differences likely reflect true differences rather than measurement bias. The impact of low precision at the upper end of the scale should be clarified. PMID- 22092022 TI - Managed care and the diffusion of endoscopy in fee-for-service Medicare. AB - OBJECTIVE: To determine whether Medicare managed care penetration impacted the diffusion of endoscopy services (sigmoidoscopy, colonoscopy) among the fee-for service (FFS) Medicare population during 2001-2006. METHODS: We model utilization rates for colonoscopy or sigmoidoscopy as impacted by both market supply and demand factors. We use spatial regression to perform ecological analysis of county-area utilization rates over two time intervals (2001-2003, 2004-2006) following Medicare benefits expansion in 2001 to cover colonoscopy for persons of average risk. We examine each technology in separate cross-sectional regressions estimated over early and later periods to assess differential effects on diffusion over time. We discuss selection factors in managed care markets and how failure to control perfectly for market selection might impact our managed care spillover estimates. RESULTS: Areas with worse socioeconomic conditions have lower utilization rates, especially for colonoscopy. Holding constant statistically the socioeconomic factors, we find that managed care spillover effects onto FFS Medicare utilization rates are negative for colonoscopy and positive for sigmoidoscopy. The spatial lag estimates are conservative and interpreted as a lower bound on true effects. Our findings suggest that managed care presence fostered persistence of the older technology during a time when it was rapidly being replaced by the newer technology. PMID- 22092023 TI - The accuracy of present-on-admission reporting in administrative data. AB - OBJECTIVE: To test the accuracy of reporting present-on-admission (POA) and to assess whether POA reporting accuracy differs by hospital characteristics. DATA SOURCES: We performed an audit of POA reporting of secondary diagnoses in 1,059 medical records from 48 California hospitals. STUDY DESIGN: We used patient discharge data (PDD) to select records with secondary diagnoses that are powerful predictors of mortality and could potentially represent comorbidities or complications among patients who either had a primary procedure of a percutaneous transluminal coronary angioplasty or a primary diagnosis of acute myocardial infarction, community-acquired pneumonia, or congestive heart failure. We modeled the relationship between secondary diagnoses POA reporting accuracy (over reporting and under-reporting) and hospital characteristics. DATA COLLECTION: We created a gold standard from blind reabstraction of the medical records and compared the accuracy of the PDD against the gold standard. PRINCIPAL FINDINGS: The PDD and gold standard agreed on POA reporting in 74.3 percent of records, with 13.7 percent over-reporting and 11.9 percent under-reporting. For-profit hospitals tended to overcode secondary diagnoses as present on admission (odds ratios [OR] 1.96; 95 percent confidence interval [CI] 1.11, 3.44), whereas teaching hospitals tended to undercode secondary diagnoses as present on admission (OR 2.61; 95 percent CI 1.36, 5.03). CONCLUSIONS: POA reporting of secondary diagnoses is moderately accurate but varies by hospitals. Steps should be taken to improve POA reporting accuracy before using POA in hospital assessments tied to payments. PMID- 22092024 TI - Solid-state nuclear magnetic resonance studies delineate the role of the protein in activation of both aromatic rings of thiamin. AB - Knowledge of the state of ionization and tautomerization of heteroaromatic cofactors when enzyme-bound is essential for formulating a detailed stepwise mechanism via proton transfers, the most commonly observed contribution to enzyme catalysis. In the bifunctional coenzyme, thiamin diphosphate (ThDP), both aromatic rings participate in catalysis, the thiazolium ring as an electrophilic covalent catalyst and the 4'-aminopyrimidine as acid-base catalyst involving its 1',4'-iminopyrimidine tautomeric form. Two of four ionization and tautomeric states of ThDP are well characterized via circular dichroism spectral signatures on several ThDP superfamily members. Yet, the method is incapable of providing information about specific proton locations, which in principle may be accessible via NMR studies. To determine the precise ionization/tautomerization states of ThDP during various stages of the catalytic cycle, we report the first application of solid-state NMR spectroscopy to ThDP enzymes, whose large mass (160,000-250,000 Da) precludes solution NMR approaches. Three de novo synthesized analogues, [C2,C6'-(13)C(2)]ThDP, [C2-(13)C]ThDP, and [N4'-(15)N]ThDP used with three enzymes revealed that (a) binding to the enzymes activates both the 4' aminopyrimidine (via pK(a) elevation) and the thiazolium rings (pK(a) suppression); (b) detection of a pre-decarboxylation intermediate analogue using [C2,C6'-(13)C(2)]ThDP, enables both confirmation of covalent bond formation and response in 4'-aminopyrimidine ring's tautomeric state to intermediate formation, supporting the mechanism we postulate; and (c) the chemical shift of bound [N4' (15)N]ThDP provides plausible models for the participation of the 1',4' iminopyrimidine tautomer in the mechanism. Unprecedented detail is achieved about proton positions on this bifunctional coenzyme on large enzymes in their active states. PMID- 22092025 TI - Detection of articular pathology of the distal aspect of the third metacarpal bone in thoroughbred racehorses: comparison of radiography, computed tomography and magnetic resonance imaging. AB - OBJECTIVE: To compare digital radiography (DR), computed tomography (CT), and magnetic resonance imaging (MRI) for detection of pathology of the distal aspect of the third metacarpal bone (MC3) and to assess whether arthrography would improve detection of articular cartilage or subchondral bone cracking. STUDY DESIGN: Cross-sectional study. SAMPLE POPULATION: Limb specimens from 17 Thoroughbred horses after catastrophic injury and 4 age-matched control horses. METHODS: Standard DR, CT, and MRI images of the metacarpophalangeal joint were acquired before and after iohexol injection. Pathologic features detected with imaging and on visual inspection of cartilage and subchondral bone of the distal aspect of MC3 were graded. Imaging observations were compared with pathologic abnormalities. RESULTS: Inspection revealed obvious changes in the cartilage and subchondral bone surfaces in Thoroughbreds. Both CT and MRI were superior to DR for detection of subchondral bone pathology. Cracking of cartilage was not detected by any imaging modality. Signal changes associated with cartilage loss and development of repair tissue were evident on MRI in 9/19 cases. There was significant correlation (P < .05) between subchondral bone pathology detected on both CT and MRI, and cartilage pathology on gross examination. Contrast arthrography did not improve the detection of articular cartilage or subchondral plate cracking. CONCLUSION: Both CT and MRI are superior to DR for detection of subchondral bone pathology, but underestimate the extent of joint adaptation and pathologic damage. MRI was able to detect cartilage degeneration. PMID- 22092026 TI - The moderating role of self-monitoring on the interpersonal aspects of attitude ambivalence. AB - Extant research has found a relation between holding conflicting attitudes with a familiar person (interpersonal discrepancy) and subjective attitude ambivalence. In 2 studies, we investigated the role of interpersonal discrepancy in the experience of attitude ambivalence as a function of self-monitoring and level of liking of the other person. Building on balance theory, we proposed and found that high (vs. low) self-monitors feel most comfortable when they are in agreement with liked (vs. disliked) others. In Study 1, 80 university students revealed that when the significant other is a parent, high self-monitors feel more subjective ambivalence when there is more interpersonal discrepancy. In Study 2, 37 university students reported their feelings of subjective ambivalence when considering the interpersonal discrepancy between liked (vs. disliked) familiar people. Again, it was high self-monitors who were most susceptible to increased feelings of subjective ambivalence, particularly for discrepancies between their own attitude and the attitude of liked others. Taken together, our 2 studies broaden our understanding of the interpersonal foundations of subjective ambivalence by suggesting that they may depend on personality differences and the nature of the social relationship. PMID- 22092027 TI - Total synthesis of polygalolide A. AB - The total synthesis of polygalolide A was accomplished through intramolecular C glycosylation of glucal modified with siloxyfuran. The siloxyfuran group and siloxy substituent at the C-3 position played crucial roles in allowing direct access to the highly substituted oxabicyclo[3.2.1] core skeleton with correct quaternary stereogenic centers. PMID- 22092028 TI - Resilience is a good predictor of hopelessness even after accounting for stressful life events, mood and personality (NEO-PI-R). AB - A better understanding of the relation between protection and vulnerability may advance our understanding of mental health. Therefore the purpose of this study was to examine the incremental validity of the Resilience Scale for Adults (RSA) as a predictor for level of hopelessness. A healthy sample (N = 532) completed the Beck Hopelessness Scale, a list of Stressful Life Events (SLE), the Hopkins Symptom Checklist-25 (HSCL-25), NEO-PI-R (NEO Personality Inventory Revised) and the RSA. The relations between the variables were explored with correlations and multiple hierarchical regression analyses. The results indicated that the RSA measures important protective factors that significantly predict lower levels of hopelessness even when accounting for age, gender, SLE, HSCL-25 and NEO-PI-R. This study supports the notion that the protective resilience factors in the RSA have unique contributions over and above established constructs of stressful life events, depressive and anxiety symptoms and personality in predicting hopelessness, supporting the incremental validity of the RSA. PMID- 22092029 TI - Predicting road test performance in drivers with dementia. AB - OBJECTIVES: To develop a cognitive and functional screening battery for the on road performance of older drivers with dementia. DESIGN: Prospective observational study. SETTING: On-road driving evaluation clinic at an academic rehabilitation center. PARTICIPANTS: Ninety-nine older people with dementia (63% male, mean age 74.2 +/- 9), referred by community physicians to an occupational therapy driving clinic. MEASUREMENTS: The outcome variable was pass or fail on the modified Washington University Road Test. Predictor measures were tests of visual, motor, and cognitive functioning, selected for their empirical or conceptual relationship to the complex task of driving safely. RESULTS: Sixty five (65%) participants failed the on-road driving test. The best predictive model, with an overall accuracy of up to 85% when participants were blinded, included the Eight-item Informant Interview to Differentiate Aging and Dementia, Clock Drawing Test score, and time to complete the Snellgrove Maze Test or Trail Making Test Part A. Visual and motor functioning were not associated with road test failure. CONCLUSION: A screening battery that could be performed in less than 10 minutes predicted with good accuracy failure rate for the on-road driving test in this sample of older drivers with dementia. A probability of failure calculator is provided from a logistic regression model that may be useful for clinicians in their decision to refer impaired older adults for further testing. More studies are needed in larger community-based samples, along with discussions with patients, families, and clinicians, with regard to acceptable levels of test uncertainty. PMID- 22092031 TI - Loss of claudin-1 in lipopolysaccharide-treated periodontal epithelium. AB - BACKGROUND AND OBJECTIVE: The epithelial barrier is a critical component of innate immunity and provides protection against microbial invasion. Claudin-1, a tight junction protein, is known to contribute to the epithelial cell barrier. An experimentally induced rat periodontal disease model was used to study the effects of lipopolysaccharide (LPS) on the expression of tight junction associated molecule genes in the junctional epithelium. MATERIAL AND METHODS: LPS was applied for 8 wk in the gingival sulcus, and junctional epithelium was collected by laser-capture microdissection and subjected to microarray analysis. RESULTS: Microarray analysis identified that expression of the claudin-1 gene was decreased in the epithelium by chronic LPS challenge. Immunohistochemical analysis confirmed the expression of claudin-1 protein in junctional epithelium and that 8 wk of chronic LPS topical application significantly reduced claudin-1 expression. The effect of LPS on claudin-1 protein expression was validated using a porcine junctional epithelial cell culture Transwell model. The epithelial barrier, as measured using transmembrane resistance, was significantly reduced after 3 wk of LPS challenge and this was associated with a decreased level of expression of claudin-1 protein. CONCLUSION: These results confirm that the initiation of experimental periodontal disease is associated with reduction in the expression of claudin-1 gene and protein. This decreased level of a critical tight junction protein may result in the disruption of barrier function and may play an important role in the initiation of periodontal disease. PMID- 22092030 TI - Molecular mechanisms of compartmentalization and biomineralization in magnetotactic bacteria. AB - Magnetotactic bacteria (MB) are remarkable organisms with the ability to exploit the earth's magnetic field for navigational purposes. To do this, they build specialized compartments called magnetosomes that consist of a lipid membrane and a crystalline magnetic mineral. These organisms have the potential to serve as models for the study of compartmentalization as well as biomineralization in bacteria. Additionally, they offer the opportunity to design applications that take advantage of the particular properties of magnetosomes. In recent years, a sustained effort to identify the molecular basis of this process has resulted in a clearer understanding of the magnetosome formation and biomineralization. Here, I present an overview of MB and explore the possible molecular mechanisms of membrane remodeling, protein sorting, cytoskeletal organization, iron transport, and biomineralization that lead to the formation of a functional magnetosome organelle. PMID- 22092032 TI - Role of water contamination within the GC column of a GasBench II peripheral on the reproducibility of 18O/16O ratios in water samples. AB - The GasBench II peripheral along with MAT 253 combination provides a more sensitive platform for the determination of water isotope ratios. Here, we examined the role of adsorbed moisture within the gas chromatography (GC) column of the GasBench II on measurement uncertainties. The uncertainty in (18)O/(16)O ratio measurements is determined by several factors, including the presence of water in the GC. The contamination of GC with water originating from samples as water vapour over a longer timeframe is a critical factor in determining the reproducibility of (18)O/(16)O ratios in water samples. The shift in isotope ratios observed in the experiment under dry and wet conditions correlates strongly with the retention time of analyte CO(2), indicating the effect of accumulated moisture. Two possible methods to circumvent or minimise the effect of adsorbed water on isotope ratios are presented here. The proposed methodology includes either the regular baking of the GC column at a higher temperature (120 degrees C) after analysis of a batch of 32 sample entries or conducting the experiment at a low GC column temperature (22.5 degrees C). The effects of water contamination on long-term reproducibility of reference water, with and without baking protocol, have been described. PMID- 22092033 TI - A comparison of health care use for physician-referred and self-referred episodes of outpatient physical therapy. AB - OBJECTIVE: To compare patient profiles and health care use for physician-referred and self-referred episodes of outpatient physical therapy (PT). DATA SOURCE: Five years (2003-2007) of private health insurance claims data, from a Midwest insurer, on beneficiaries aged 18-64. STUDY DESIGN: Retrospective analyses of health care use of physician-referred (N = 45,210) and self-referred (N = 17,497) ambulatory PT episodes of care was conducted, adjusting for age, gender, diagnosis, case mix, and year. DATA COLLECTION/EXTRACTION: Physical therapy episodes began with the physical therapist initial evaluation and ended on the last date of service before 60 days of no further visits. Episodes were classified as physician-referred if the patient had a physician claim from a reasonable referral source in the 30 days before the start of PT. PRINCIPAL FINDINGS: The self-referred group was slightly younger, but the two groups were very similar in regard to diagnosis and case mix. Self-referred episodes had fewer PT visits (86 percent of physician-referred) and lower allowable amounts ($0.87 for every $1.00), after covariate adjustment, but did not differ in related health care utilization after PT. CONCLUSIONS: Health care use during PT episodes was lower for those who self-referred, after adjusting for key variables, but did not differ after the PT episode. PMID- 22092034 TI - Recurrence of empty follicle syndrome with stimulated IVF cycles. AB - AIM: To determine the incidence of recurrent empty follicle syndrome (EFS) and to analyse the factors associated with this phenomenon. METHODS: Retrospective analysis comparing all EFS cycles with cycles in which oocytes were retrieved in our in vitro fertilization (IVF) unit between 1998 and 2006. RESULTS: Of 8292 IVF cycles, 163 (2.0%) resulted in empty follicles. Risk factors for EFS included advanced age (37.7 +/- 6.0 years vs. 34.2 +/- 6.0 years, p < 0.001), longer infertility (8.8 +/- 10.6 years vs. 6.3 +/- 8.4 years, p < 0.05), higher baseline follicle-stimulating hormone levels (8.7 +/- 4.7 IU/L vs. 6.7 +/- 2.9 IU/L, p < 0.001) and lower E2 levels before the human chorionic gonadotropin injection (499.9 +/- 480.9 pg/mL vs. 1516.3 +/- 887.5 pg/mL, p < 0.001) compared with cases in which ova were retrieved. Among patients with EFS, recurrent EFSs occurred in 15.8% of subsequent cycles. CONCLUSION: The EFS is a sporadic event in the majority of patients. However, in about 16% of the patients, EFS may recur. These cases may be a variant form of poor response and patients with repetitive EFS syndrome should be counseled concerning their chances to conceive. PMID- 22092035 TI - Socioeconomic status and smoking: a review. AB - Smoking prevalence is higher among disadvantaged groups, and disadvantaged smokers may face higher exposure to tobacco's harms. Uptake may also be higher among those with low socioeconomic status (SES), and quit attempts are less likely to be successful. Studies have suggested that this may be the result of reduced social support for quitting, low motivation to quit, stronger addiction to tobacco, increased likelihood of not completing courses of pharmacotherapy or behavioral support sessions, psychological differences such as lack of self efficacy, and tobacco industry marketing. Evidence of interventions that work among lower socioeconomic groups is sparse. Raising the price of tobacco products appears to be the tobacco control intervention with the most potential to reduce health inequalities from tobacco. Targeted cessation programs and mass media interventions can also contribute to reducing inequalities. To tackle the high prevalence of smoking among disadvantaged groups, a combination of tobacco control measures is required, and these should be delivered in conjunction with wider attempts to address inequalities in health. PMID- 22092036 TI - Accuracy of various human NAT2 SNP genotyping panels to infer rapid, intermediate and slow acetylator phenotypes. AB - AIM: Humans exhibit genetic polymorphism in NAT2 resulting in rapid, intermediate and slow acetylator phenotypes. Over 65 NAT2 variants possessing one or more SNPs in the 870-bp NAT2 coding region have been reported. The seven most frequent SNPs are rs1801279 (191G>A), rs1041983 (282C>T), rs1801280 (341T>C), rs1799929 (481C>T), rs1799930 (590G>A), rs1208 (803A>G) and rs1799931 (857G>A). The majority of studies investigate the NAT2 genotype assay for three SNPs: 481C>T, 590G>A and 857G>A. A tag-SNP (rs1495741) recently identified in a genome-wide association study has also been proposed as a biomarker for the NAT2 phenotype. MATERIALS & METHODS: Sulfamethazine N-acetyltransferase catalytic activities were measured in cryopreserved human hepatocytes from a convenience sample of individuals in the USA with an ethnic frequency similar to the 2010 US population census. These activities were segregated by the tag-SNP rs1495741 and each of the seven SNPs described above. We assessed the accuracy of the tag-SNP and various two-, three-, four- and seven-SNP genotyping panels for their ability to accurately infer NAT2 phenotype. RESULTS: The accuracy of the various NAT2 SNP genotype panels to infer NAT2 phenotype were as follows: seven-SNP: 98.4%; tag SNP: 77.7%; two-SNP: 96.1%; three-SNP: 92.2%; and four-SNP: 98.4%. CONCLUSION: A NAT2 four-SNP genotype panel of rs1801279 (191G>A), rs1801280 (341T>C), rs1799930 (590G>A) and rs1799931 (857G>A) infers NAT2 acetylator phenotype with high accuracy, and is recommended over the tag-, two-, three- and (for economy of scale) the seven-SNP genotyping panels, particularly in populations of non European ancestry. PMID- 22092037 TI - A standardized protocol for the perioperative management of myasthenia gravis patients. Experience with 110 patients. AB - BACKGROUND: Video-assisted thoracoscopic extended thymectomy (VATET) is well established in the treatment of myasthenia gravis; however, patient selection remains controversial. Perioperative management protocol is lacking, and concerns regarding post-operative myasthenic crisis still remain. We performed a retrospective observational study evaluating the impact of the introduction of a protocol in the perioperative management of patients with myasthenia gravis who underwent VATET. METHODS: The perioperative management protocol was developed by a team of neurologists and anesthesiologists who reviewed the literature and their previous experience on myasthenia gravis patients. Respiratory, clinical, and neurological patient features were included in the protocol evaluation. A retrospective review of patients who underwent VATET before and after introduction to the protocol was finally performed. RESULTS: The medical records of 66 patients (pre-protocol group) and 44 patients (protocol group) were available for the study. In the pre-protocol group, 17 patients (26%) were admitted to intensive care unit (ICU) during the post-operative period, while three patients (6.8%) of the protocol group met the criteria for ICU post operative admission. This resulted in a reduction of 73.5% of patients admitted to ICU (P = 0.023) and in an 80% (P = 0.002) reduction of the use neuromuscular blocking agents. Two post-operative myasthenic crises preceded by bulbar symptoms (1.8%) were identified in the pre-protocol group patients. CONCLUSIONS: Although the application of our protocol results in a substantial reduction in the recovery of patients in the ICU and in hospital costs, there was no substantial difference in mortality and morbidity between patients admitted to the surgical ward or to ICU. PMID- 22092038 TI - Activator protein-1 (AP-1) signalling in human atherosclerosis: results of a systematic evaluation and intervention study. AB - Animal studies implicate the AP-1 (activator protein-1) pro-inflammatory pathway as a promising target in the treatment of atherosclerotic disease. It is, however, unclear whether these observations apply to human atherosclerosis. Therefore we evaluated the profile of AP-1 activation through histological analysis and tested the potential benefit of AP-1 inhibition in a clinical trial. AP-1 activation was quantified by phospho-c-Jun nuclear translocation (immunohistochemistry) on a biobank of aortic wall samples from organ donors. The effect of AP-1 inhibition on vascular parameters was tested through a double blind placebo-controlled cross-over study of 28 days doxycycline or placebo in patients with symptomatic peripheral artery disease. Vascular function was assessed by brachial dilation as well as by plasma samples analysed for hs-CRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6), IL-8, ICAM-1 (intercellular adhesion molecule-1), vWF (von Willebrand factor), MCP-1 (monocyte chemoattractant protein-1), PAI-1 (plasminogen activator inhibitor-1) and fibrinogen. Histological evaluation of human atherosclerosis showed minimal AP-1 activation in non-diseased arterial wall (i.e. vessel wall without any signs of atherosclerotic disease). A gradual increase of AP-1 activation was found in non progressive and progressive phases of atherosclerosis respectively (P<0.044). No significant difference was found between progressive and vulnerable lesions. The expression of phospho-c-Jun diminished as the lesion stabilized (P<0.016) and does not significantly differ from the normal aortic wall (P<0.33). Evaluation of the doxycycline intervention only revealed a borderline-significant reduction of circulating hs-CRP levels (-0.51 MUg/ml, P=0.05) and did not affect any of the other markers of systemic inflammation and vascular function. Our studies do not characterize AP-1 as a therapeutic target for progressive human atherosclerotic disease. PMID- 22092039 TI - Mn2+ complexes with 12-membered pyridine based macrocycles bearing carboxylate or phosphonate pendant arm: crystallographic, thermodynamic, kinetic, redox, and 1H/17O relaxation studies. AB - Mn(2+) complexes represent an alternative to Gd(3+) chelates which are widely used contrast agents in magnetic resonance imaging. In this perspective, we investigated the Mn(2+) complexes of two 12-membered, pyridine-containing macrocyclic ligands bearing one pendant arm with a carboxylic acid (HL(1), 6 carboxymethyl-3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene) or a phosphonic acid function (H(2)L(2), 6-dihydroxyphosphorylmethyl-3,6,9,15 tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene). Both ligands were synthesized using nosyl or tosyl amino-protecting groups (starting from diethylenetriamine or tosylaziridine). The X-ray crystal structures confirmed a coordination number of 6 for Mn(2+) in their complexes. In aqueous solution, these pentadentate ligands allow one free coordination site for a water molecule. Potentiometric titration data indicated a higher basicity for H(2)L(2) than that for HL(1), related to the electron-donating effect of the negatively charged phosphonate group. According to the protonation sequence determined by (1)H and (31)P pH-NMR titrations, the first two protons are attached to macrocyclic amino groups whereas the subsequent protonation steps occur on the pendant arm. Both ligands form thermodynamically stable complexes with Mn(2+), with full complexation at physiological pH and 1:1 metal to ligand ratio. The kinetic inertness was studied via reaction with excess of Zn(2+) under various pHs. The dissociation of MnL(2) is instantaneous (at pH 6). For MnL(1), the dissociation is very fast (k(obs) = 1-12 * 10(3) s(-1)), much faster than that for MnDOTA, MnNOTA, or the Mn(2+) complex of the 15-membered analogue. It proceeds exclusively via the dissociation of the monoprotonated complex, without any influence of Zn(2+). In aqueous solution, both complexes are air-sensitive leading to Mn(3+) species, as evidenced by UV-vis and (1)H NMRD measurements and X-ray crystallography. Cyclic voltammetry gave low oxidation peak potentials (E(ox) = 0.73 V for MnL(1) and E(ox) = 0.68 V for MnL(2)), in accordance with air oxidation. The parameters governing the relaxivity of the Mn(2+) complexes were determined from variable-temperature (17)O NMR and (1)H NMRD data. The water exchange is extremely fast, k(ex) = 3.03 and 1.77 * 10(9) s(-1) for MnL(1) and MnL(2), respectively. Variable-pressure (17)O NMR measurements have been performed to assess the water exchange mechanism on MnL(1) and MnL(2) as well as on other Mn(2+) complexes. The negative activation volumes for both MnL(1) and MnL(2) complexes confirmed an associative mechanism of the water exchange as expected for a hexacoordinated Mn(2+) ion. The hydration number of q = 1 was confirmed for both complexes by (17)O chemical shifts. A relaxometric titration with phosphate, carbonate or citrate excluded the replacement of the coordinated water molecule by these small endogenous anions. PMID- 22092040 TI - Methodological reporting in qualitative, quantitative, and mixed methods health services research articles. AB - OBJECTIVES: Methodologically sound mixed methods research can improve our understanding of health services by providing a more comprehensive picture of health services than either method can alone. This study describes the frequency of mixed methods in published health services research and compares the presence of methodological components indicative of rigorous approaches across mixed methods, qualitative, and quantitative articles. DATA SOURCES: All empirical articles (n = 1,651) published between 2003 and 2007 from four top-ranked health services journals. STUDY DESIGN: All mixed methods articles (n = 47) and random samples of qualitative and quantitative articles were evaluated to identify reporting of key components indicating rigor for each method, based on accepted standards for evaluating the quality of research reports (e.g., use of p-values in quantitative reports, description of context in qualitative reports, and integration in mixed method reports). We used chi-square tests to evaluate differences between article types for each component. PRINCIPAL FINDINGS: Mixed methods articles comprised 2.85 percent (n = 47) of empirical articles, quantitative articles 90.98 percent (n = 1,502), and qualitative articles 6.18 percent (n = 102). There was a statistically significant difference (chi(2) (1) = 12.20, p = .0005, Cramer's V = 0.09, odds ratio = 1.49 [95% confidence interval = 1,27, 1.74]) in the proportion of quantitative methodological components present in mixed methods compared to quantitative papers (21.94 versus 47.07 percent, respectively) but no statistically significant difference (chi(2) (1) = 0.02, p = .89, Cramer's V = 0.01) in the proportion of qualitative methodological components in mixed methods compared to qualitative papers (21.34 versus 25.47 percent, respectively). CONCLUSION: Few published health services research articles use mixed methods. The frequency of key methodological components is variable. Suggestions are provided to increase the transparency of mixed methods studies and the presence of key methodological components in published reports. PMID- 22092041 TI - Punishment has a lasting impact on error-related brain activity. AB - The current study examined whether punishment has direct and lasting effects on error-related brain activity, and whether this effect is larger with increasing trait anxiety. Participants were told that errors on a flanker task would be punished in some blocks but not others. Punishment was applied following 50% of errors in punished blocks during the first half of the experiment (i.e., acquisition), but never in the second half (i.e., extinction). The ERN was enhanced in the punished blocks in both experimental phases--this enhancement remained stable throughout the extinction phase. More anxious individuals were characterized by larger punishment-related modulations in the ERN. The study reveals evidence for lasting, punishment-based modulations of the ERN that increase with anxiety. These data suggest avenues for research to examine more specific learning-related mechanisms that link anxiety to overactive error monitoring. PMID- 22092042 TI - Preparation of azithromycin nanosuspensions by reactive precipitation method. AB - PURPOSE: The aim of this work was to prepare azithromycin (AZI) nanosuspensions to increase the solubility and dissolution rate. METHOD: AZI nanosuspensions were prepared by the combination of reactive precipitation and freeze-drying in presence of biocompatible stabilizer. Formulation and process variables affecting the characteristics of nanosuspensions were optimized. Various tests were carried out to study the physicochemical characteristics of AZI nanosuspensions. RESULTS: The nanosuspensions were parenterally acceptable and autoclavable, because soybean lecithin was the stabilizer of choice and no organic solvents were used during the preparation. The mean particle size and zeta potential of the AZI nanosuspensions were about 200 nm (+/-20 nm) and -36.7 mV (+/-7.6 mV), respectively. Solid nanoparticles were obtained by lyophilization of the nanosuspensions and nanosuspensions rapidly reconstituted when the nanoparticles were dispersed in water. X-ray diffraction and differential scanning calorimetry analysis showed that the crystal state of nanoparticles was amorphous. Solubility and in vitro release studies indicated that the saturated solubility and dissolution rate increased obviously in comparison of raw AZI. The nanoparticles were physically stable over a period of 5 months as demonstrated by unchanged crystallinity and stable particle size when stored at room temperature and protected from humidity. CONCLUSION: The results suggested that reactive precipitation is an effective way to prepare AZI nanosuspensions with increased solubility and dissolution rate. PMID- 22092043 TI - A structurally simple self-immolative reagent that provides three distinct, simultaneous responses per detection event. AB - A general design is presented for a stimulus-responsive small molecule that is capable of responding to a specific applied chemical or physical signal by releasing two different types of pendant small molecules and a colorimetric indicator simultaneously. A key aspect of this design is the ease with which these reagents are prepared: typically, only four synthetic steps are required. Moreover, the modular construction strategy provides access to stimuli-responsive reagents that are capable of (i) responding to a variety of applied signals and (ii) releasing a number of different small molecules that contain primary alcohols, secondary alcohols, or phenols. These stimuli-responsive reagents are stable under physiological conditions (neither hydrolysis nor thermal degradation of the reagent occurs in significant quantity), and when they are exposed to the appropriate applied signal, they release both pendant small molecules and the colorimetric indicator completely within hours. Finally, unlike other functional groups, such as carbonates, that are used to connect alcohol-bearing molecules to controlled-release reagents, the linkage described in this article increases in hydrolytic stability (rather than decreases) as the pK(a) of the pendant alcohol decreases. PMID- 22092044 TI - Associations between cytomegalovirus infection and functional impairment and frailty in the BELFRAIL Cohort. AB - OBJECTIVES: To investigate whether an observed association between cytomegalovirus (CMV) exposure and functional impairment and frailty in older adults is reproducible in a cohort of individuals aged 80 and older. DESIGN: The baseline results of the BELFRAIL study, a prospective observational cohort study, were analyzed. SETTING: Three well-circumscribed areas of Belgium. PARTICIPANTS: Five hundred sixty-seven persons aged 80 and older recruited by 29 general practitioners. MEASUREMENTS: Serum samples were assayed for levels of CMV immunoglobulin (Ig)G antibodies, interleukin (IL)-6, and C-reactive protein. Measures of functional impairment were the Physical Performance Battery, Activities of Daily Living, and the Mini-Mental State Examination. Frailty was assessed using the Fried criteria. RESULTS: Positive CMV serology was found in 74% of the population, 61% of whom had a high anti-CMV IgG titer (>250 IU/mL). CMV infection was not associated with functional or cognitive impairment. Positive CMV serology was negatively associated with prevalent frailty after adjusting for age, sex, level of education, comorbidity, smoking status, body mass index, and IL-6 level. High levels of anti-CMV IgG were associated with functional impairment. In the adjusted models, this relationship was no longer statistically significant. There was no association between prevalent frailty or cognitive impairment and high anti-CMV IgG titers. CONCLUSION: The findings of previous studies could not be confirmed. Moreover, positive CMV serology was found to be negatively associated with frailty. These apparently contradictory results may reflect a survival effect because the current study population was considerably older than the populations of older adults in previous studies. PMID- 22092045 TI - Narcissism in midlife: longitudinal changes in and correlates of women's narcissistic personality traits. AB - We examined changes in and correlates of 3 kinds of narcissism--hypersensitivity, willfulness, and autonomy--during middle adulthood. Few studies have examined narcissistic personality traits beyond young adulthood, and none has assessed longitudinal changes in narcissism during midlife. In a sample of 70 college educated women, we found that observer ratings of hypersensitive narcissism were associated with more negative outcomes at ages 43 and 53 (i.e., more depressive symptoms and physical health problems, lower life satisfaction and well-being). Ratings of willfulness and autonomy predicted more positive outcomes. All 3 kinds of narcissism showed considerable rank-order stability over 10 years, but there were also mean-level changes: Hypersensitivity and autonomy decreased, whereas willfulness increased. More positive outcomes were associated with decreases in hypersensitivity and increases in willfulness and autonomy. However, in multivariate analyses, autonomy did not show any significant associations with women's health and well-being outcomes, suggesting that it may have less predictive utility compared to hypersensitivity and willfulness. Our findings highlight developmental changes in and correlates of women's narcissistic personality traits and the importance of assessing different aspects of narcissism in midlife. PMID- 22092046 TI - Neuropsychological function and past exposure to metallic mercury in female dental workers. AB - The aim of this study was to see if dental personnel with previous exposure to metallic mercury have later developed disturbances in cognitive function. Ninety one female participants who had been selected from a previous health survey of dental personnel were investigated neuropsychologically within the following domains: motor function, short-term memory, working memory, executive function, mental flexibility, and visual and verbal long-term memory. The scores were mainly within normal ranges. Relationships between an exposure score, the duration of employment before 1990, and previously measured mercury in urine as independent variables and the neuropsychological findings as dependent variables, were analyzed by multiple linear regression controlling for age, general ability, length of education, alcohol consumption, and previous head injuries. The only relationship that was statistically significant in the hypothesized direction was between the previously measured urine mercury values and visual long-term memory, where the urine values explained 30% of the variability. As the study had a low statistical power and also some other methodological limitations, the results have to be interpreted with caution. Even so, we think it is right to conclude that neuropsychological findings indicative of subsequent cognitive injuries are difficult to find in groups of otherwise healthy dental personnel with previous occupational exposure to mercury. PMID- 22092047 TI - Does cognitive impairment affect rehabilitation outcome? AB - OBJECTIVES: To assess how cognitive impairment affects rehabilitation outcomes and to determine whether individual benefit regardless of cognition. DESIGN: Prospective open observational study. SETTING: Two rehabilitation wards admitting older adults after admissions with medical or surgical problems. PARTICIPANTS: Two hundred forty-one individuals admitted to two rehabilitation wards, 144 female, mean age 84.4 +/- 7.3 (range: 59-103). MEASUREMENTS: The Mini-Mental State Examination (MMSE) was administered, and participants were categorized into four groups: cognitively intact (MMSE score: 27-30), mildly impaired (MMSE score: 21-26), moderately impaired (MMSE score: 11-20), and severely impaired (MMSE score: 0-10). Barthel activity of daily living score was calculated on admission, at 2 and 6 weeks (if appropriate), and at discharge to assess level of independence and improvement or deterioration in function. Information relating to mortality, discharge destination, and length of stay was also collected. RESULTS: After adjusting for comorbidities and age, all four groups showed improvement in Barthel score from admission to discharge. This improvement was highly significant (P = .005) in participants with normal cognition and mild to moderate impairment. Severely impaired participants also made significant improvement (P = .01). Length of stay was significantly longer for participants with lower cognitive scores. Discharge of 50% of participants occurred by 26, 28, 38, and 47 days for Groups 1 to 4, respectively (P = .001). Higher rates of institutionalization and mortality (P = .02) were associated with lower MMSE score. CONCLUSION: All participants improved functionally regardless of cognition. Likelihood of institutionalization, mortality, length of stay, and adverse incidents was higher with lower MMSE scores. PMID- 22092048 TI - When 'UPS' fails to deliver: a novel gene associated with the ubiquitin proteasome system causes familial ALS. PMID- 22092050 TI - Identifying sources and processes controlling the sulphur cycle in the Canyon Creek watershed, Alberta, Canada. AB - Sources and processes affecting the sulphur cycle in the Canyon Creek watershed in Alberta (Canada) were investigated. The catchment is important for water supply and recreational activities and is also a source of oil and natural gas. Water was collected from 10 locations along an 8 km stretch of Canyon Creek including three so-called sulphur pools, followed by the chemical and isotopic analyses on water and its major dissolved species. The delta(2)H and delta(18)O values of the water plotted near the regional meteoric water line, indicating a meteoric origin of the water and no contribution from deeper formation waters. Calcium, magnesium and bicarbonate were the dominant ions in the upstream portion of the watershed, whereas sulphate was the dominant anion in the water from the three sulphur pools. The isotopic composition of sulphate (delta(34)S and delta(18)O) revealed three major sulphate sources with distinct isotopic compositions throughout the catchment: (1) a combination of sulphate from soils and sulphide oxidation in the bedrock in the upper reaches of Canyon Creek; (2) sulphide oxidation in pyrite-rich shales in the lower reaches of Canyon Creek and (3) dissolution of Devonian anhydrite constituting the major sulphate source for the three sulphur pools in the central portion of the watershed. The presence of H(2)S in the sulphur pools with delta(34)S values ~30 0/00 lower than those of sulphate further indicated the occurrence of bacterial (dissimilatory) sulphate reduction. This case study reveals that delta(34)S values of surface water systems can vary by more than 20 0/00 over short geographic distances and that isotope analyses are an effective tool to identify sources and processes that govern the sulphur cycle in watersheds. PMID- 22092051 TI - Chemical composition and antioxidant properties of gamma-irradiated Iranian Zataria multiflora extracts. AB - CONTEXT: Irradiation is the process of exposing food such as herbal plant to ionizing radiation to destroy microorganisms. Zataria multiflora Boiss (Lamiaceae), known as Avishan-e-Shirazi in Persian, is a thyme-like plant that grows naturally in central and southern parts of Iran and is used in traditional folk medicine. OBJECTIVE: In this study, the effects of gamma-radiation on chemical composition and antioxidant properties of Z. multiflora were investigated. MATERIALS AND METHODS: The plants were first irradiated with Co60 source (0, 10, and 25 kGy) and then subjected to Clevenger extraction to obtain essential oils. The composition of the oil was analyzed by a gas chromatography and compared with samples pretreated under different conditions. In parallel, the hydroalcoholic extract was prepared and used for measuring flavonoid content. Thereafter, the free-radical scavenging and antioxidant properties of essential oils and hydroalcoholic extract were examined. RESULTS: Despite the minor change in the individual oil constituents, the total percentage of the main components remained unaffected before and after irradiation (~95%). In addition, the total flavonoid content of hydroalcoholic extract was also unchanged due to irradiation (~32 mg QE/g extract). The high radical scavenging activity of the oil (~67%) and hydroalcoholic extract (~71%), in addition, the antioxidant properties of the oil (~91%) and hydroalcoholic extract (~95%), were unaffected after irradiation. DISCUSSION AND CONCLUSIONS: These findings may suggest the sustainability of Z. multiflora extract properties pretreated with gamma-radiation. With a view to its antioxidant applications, resistance of Z. multiflora and its properties against radiation effects are promising findings. PMID- 22092058 TI - Synthesis and structural characterization of 1,2,4-diazaphospholide complexes of titanium(IV) and titanium(III). AB - Two 1,2,4-diazaphospholide complexes of [Ti(eta(2)-3,5-Ph(2)dp)(4)] and paramagnetic [Ti(eta(2)-3,5-tBu(2)dp)(3)] were prepared by the reaction of tetrakis(dimethylamido)titanium(IV) with 3,5-diphenyl-1,2,4-diazaphophole, H[3,5 Ph(2)dp], or by the treatment of 3,5-tert-butyl-1,2,4-diazaphopholide potassium, K[3,5-tBu(2)dp], with titanium trichloride. Complexes can be viewed as the core of P(sigma(2)lambda(3))-functionalized metallodendrimers, in which the metal atoms are exclusively eta(2)(N,N) bonding to the 1,2,4-diazaphospholides while P atoms (sigma(2)lambda(3)) with electron lone pairs are located on the periphery of the molecules. PMID- 22092059 TI - Phosphonate monoesters as carboxylate-like linkers for metal organic frameworks. AB - Bidentate phosphonate monoesters are analogues of popular dicarboxylate linkers in MOFs, but with an alkoxy tether close to the coordinating site. Herein, we report 3-D MOF materials based upon phosphonate monoester linkers. Cu(1,4 benzenediphosphonate bis(monoalkyl ester), CuBDPR, with an ethyl tether is nonporous; however, the methyl tether generates an isomorphous framework that is porous and captures CO(2) with a high isosteric heat of adsorption of 45 kJ mol( 1). Computational modeling reveals that the CO(2) uptake is extremely sensitive both to the flexing of the structure and to the orientation of the alkyl tether. PMID- 22092060 TI - State-level variations in racial disparities in life expectancy. AB - OBJECTIVE: To explore state patterns in the racial life expectancy gap. DATA SOURCES: The 1997-2004 Multiple Cause of Death PUF, 2000 U.S. Census. STUDY DESIGN: We calculated life expectancy at birth for black and white men and women. DATA EXTRACTION METHODS: Data were obtained by the NCHS and U.S. Census Bureau. PRINCIPAL FINDINGS: States with small racial differences are due to higher-than expected life expectancy for blacks or lower-than-expected for whites. States with large disparity are explained by higher-than-average life expectancy among whites or lower-than-average life expectancy among blacks. CONCLUSIONS: Heterogeneous state patterns in racial disparity in life expectancy exist. Eliminating disparity in states with large black populations would make the greatest impact nationally. PMID- 22092061 TI - Dermal uptake study with 4,4'-diphenylmethane diisocyanate led to active sensitization. AB - BACKGROUND: To investigate the dermal uptake of 4,4'-diphenylmethane diisocyanate (4,4'-MDI), a study was performed in which 2 female volunteers were exposed to 10 and 25 mg, respectively, of 4,4'-MDI by applying 2.0% 4,4'-MDI in petrolatum over areas where the surface concentration corresponded to 800 ug/cm(2) . Ten days later, they developed eczematous dermatitis at the area of application. OBJECTIVES: To investigate whether the dermal application caused active sensitization to 4,4'-MDI. METHODS: Chemical analysis of the 4,4'-MDI preparation used in the application and the amount of 4,4'-MDI not absorbed by the skin was performed with liquid chromatography-mass spectrometry. The volunteers were tested with serial dilutions of 4,4'-MDI and the potentially cross-reacting substances 4,4'-diaminodiphenylmethane (4,4'-MDA), p-phenylenediamine (PPD), and dicyclohexylmethane-4,4'-diisocyanate (DMDI). RESULTS: Patch test results suggested that the volunteers were actively sensitized to 4,4'-MDI following the dermal uptake study, as they reacted positively to 4,4'-MDA, a marker for 4,4' MDI allergy. No positive reactions were seen to PPD or DMDI. Chemical investigation confirmed that the correct concentration had been used for the dermal uptake study, and showed that about 70% of the applied 4,4'-MDI was not absorbed. CONCLUSIONS: A dermal uptake study with 4,4'-MDI in 2.0% pet. with an occlusion time of 8 hr induced active sensitization to 4,4'-MDI and subsequently to 4,4'-MDA. PMID- 22092062 TI - Effect of cannabidiol on human gingival fibroblast extracellular matrix metabolism: MMP production and activity, and production of fibronectin and transforming growth factor beta. AB - BACKGROUND AND OBJECTIVE: Marijuana (Cannabis sativa) use may be associated with gingival enlargement, resembling that caused by phenytoin. Cannabidiol (CBD), a nonpsychotropic Cannabis derivative, is structurally similar to phenytoin. While there are many reports on effects of phenytoin on human gingival fibroblasts, there is no information on effects of Cannabis components on these cells. The objective of this study was to determine effects of CBD on human gingival fibroblast fibrogenic and matrix-degrading activities. MATERIAL AND METHODS: Fibroblasts were incubated with CBD in serum-free medium for 1-6 d. The effect of CBD on cell viability was determined by measuring activity of a mitochondrial enzyme. The fibrogenic molecule transforming growth factor beta and the extracellular matrix molecule fibronectin were measured by ELISA. Pro-MMP-1 and total MMP-2 were measured by ELISA. Activity of MMP-2 was determined via a colorimetric assay in which a detection enzyme is activated by active MMP-2. Data were analysed using ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: Cannabidiol had little or no significant effect on cell viability. Low CBD concentrations increased transforming growth factor beta production by as much as 40% (p < 0.001), while higher concentrations decreased it by as much as 40% (p < 0.0001). Cannabidiol increased fibronectin production by as much as approximately 100% (p < 0.001). Lower CBD concentrations increased MMP production, but the highest concentrations decreased production of both MMPs (p < 0.05) and decreased MMP-2 activity (p < 0.02). CONCLUSION: The data suggest that the CBD may promote fibrotic gingival enlargement by increasing gingival fibroblast production of transforming growth factor beta and fibronectin, while decreasing MMP production and activity. PMID- 22092063 TI - Preparation and characterization of magnetic alginate-chitosan hydrogel beads loaded matrine. AB - The aim of this study was to use alginate-chitosan (Alg-CS) hydrogel beads for developing an oral water-soluble drug delivery system, occupying pH-sensitive property and superparamagnetic. Matrine as a model drug was loaded in Alg-CS hydrogel beads to study the release character of the delivery system. The amount of matrine released from the beads was relatively low in pH 2.5 over 8 h (34.90%), but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 8 h. The results demonstrated that Alg-CS hydrogel beads possess unique pH-dependent swelling behaviors. In addition, the magnetic beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometry and vibrating-sample magnetometry. Magnetometer measurements data suggested that Alg-CS beads also had superparamagnetic property as well as fast magnetic response. It can be expected that the beads can deliver and release encapsulated anticancer agent at the tumor by the weak magnetic field, and hence could be potential candidates as an orally administered drug delivery system. PMID- 22092064 TI - Is the P3 amplitude reduction seen in externalizing psychopathology attributable to stimulus sequence effects? AB - P3 amplitude reduction (P3-AR) is associated with biological vulnerability to a spectrum of externalizing (EXT) disorders, such as conduct disorder, antisocial behavior, and substance use disorders. P3 amplitude, however, can be affected by the context within which it is measured, for example, by the position of the target in the sequence of stimuli during an oddball task. We hypothesized that EXT-related P3-AR may be due to attention or working memory deficits in EXT that would weaken these stimulus sequence effects. Using a community-based sample of adolescent males, we examined the relationship between P3 and EXT as a function of the number of standards preceding the target. Higher EXT was associated with significantly smaller P3 amplitude, regardless of the number of standards preceding the target. These results suggest that P3-AR in EXT does not vary as a function of stimulus sequence, further supporting P3-AR as an endophenotype for EXT disorders. PMID- 22092066 TI - The dynamic role of personality states in mediating the relationship between extraversion and positive affect. AB - One of the most noteworthy and robust findings in personality psychology is the relationship between extraversion and positive affect. Existing theories have debated the origins and nature of this relationship, offering both structural/fixed and environmental/dynamic explanations. We tested the novel and straightforward dynamic hypothesis that part of the reason trait extraversion predicts trait positive affect is through an increased propensity to enact extraverted states, which in turn leads to experiencing more positive affect states. We report 5 experience sampling studies (and a meta-analysis of primary studies) conducted in natural environments and laboratory settings in which undergraduate participants (N = 241) provided ratings of trait extraversion, trait positive affect, extraversion states, and positive affect states. Results of primary studies and the meta-analysis showed that relationships between trait extraversion and trait positive affect were partially mediated by aggregated extraversion states and aggregated positive affect states. The results supported our dynamic hypothesis and suggested that dynamic explanations of the relationship between trait extraversion and trait positive affect are compatible with structural explanations. An important implication of these findings is that individuals might be able to increase their happiness by self-regulating their extraverted states. PMID- 22092065 TI - A growing family: the expanding universe of the bacterial cytoskeleton. AB - Cytoskeletal proteins are important mediators of cellular organization in both eukaryotes and bacteria. In the past, cytoskeletal studies have largely focused on three major cytoskeletal families, namely the eukaryotic actin, tubulin, and intermediate filament (IF) proteins and their bacterial homologs MreB, FtsZ, and crescentin. However, mounting evidence suggests that these proteins represent only the tip of the iceberg, as the cellular cytoskeletal network is far more complex. In bacteria, each of MreB, FtsZ, and crescentin represents only one member of large families of diverse homologs. There are also newly identified bacterial cytoskeletal proteins with no eukaryotic homologs, such as WACA proteins and bactofilins. Furthermore, there are universally conserved proteins, such as the metabolic enzyme CtpS, that assemble into filamentous structures that can be repurposed for structural cytoskeletal functions. Recent studies have also identified an increasing number of eukaryotic cytoskeletal proteins that are unrelated to actin, tubulin, and IFs, such that expanding our understanding of cytoskeletal proteins is advancing the understanding of the cell biology of all organisms. Here, we summarize the recent explosion in the identification of new members of the bacterial cytoskeleton and describe a hypothesis for the evolution of the cytoskeleton from self-assembling enzymes. PMID- 22092067 TI - Comparison of the effects of two screw insertion patterns on bone fragment translocation in a 3.5 mm dynamic compression plate and a 3.5 mm limited-contact dynamic compression plate. AB - OBJECTIVE: To compare the effects of screw insertion pattern, plate type, application of bone reduction forceps, and additional load screw insertion in an 8-hole 3.5 mm dynamic compression plate (DCP) and limited-contact dynamic compression plate (LC-DCP) on bone fragment translocation (BFT) in a fracture gap model. STUDY DESIGN: In vitro mechanical study. METHODS: Two screw insertion patterns were tested in the DCP and newly redesigned LC-DCP using gap model synthetic bone constructs. In Pattern 1, screws were first inserted into the holes at each end of the plate, then screws were inserted into the holes adjacent to the fracture gap. In Pattern 2, screws were only inserted into the holes adjacent to the fracture gap. The effects of tight or loose bone forceps securing the plate, loosening a neutral screw in Pattern 1, and inserting up to 4 additional load screws with each pattern were tested. Changes in the fracture gap were measured after insertion of all neutral screws and after each load screw. RESULTS: Pattern 2 BFT was significantly greater than Pattern 1 BFT when bone forceps were loose with both plates (P < .001). In the DCP, the BFT was significantly increased by loosening the bone forceps with Pattern 2 (P < .001) and by loosening 1 neutral screw in Pattern 1 (P < .001). The BFT for each additional load screw inserted was significantly less than 1.0 mm. CONCLUSIONS: A tight neutral screw in the same bone fragment as the load screw or bone clamps that tightly secure the plate to the bone can limit BFT. PMID- 22092068 TI - Integrated model for providing tactical emergency medicine support (TEMS): analysis of 120 tactical situations. AB - BACKGROUND: Various models for organising tactical emergency medicine support (TEMS) in law enforcement operations exist. In Helsinki, TEMS is organised as an integral part of emergency medical service (EMS) and applied in hostage, siege, bomb threat and crowd control situations and in other tactical situations after police request. Our aim was to analyse TEMS operations, patient profile, and the level of on-site care provided. METHODS: We conducted a retrospective cohort study of TEMS operations in Helsinki from 2004 to 2009. Data were retrieved from EMS, hospital and dispatching centre files and from TEMS reports. RESULTS: One hundred twenty TEMS operations were analysed. Median time from dispatching to arrival on scene was 10 min [Interquartile Range (IQR) 7-14]. Median duration of operations was 41 min (IQR 19-63). Standby was the only activity in 72 operations, four patients were dead on arrival, 16 requests were called off en route and patient examination or care was needed in 28 operations. Twenty-eight patients (records retrieved) were alive on arrival and were classified as trauma (n = 12) or medical (n = 16). Of traumas, two sustained a gunshot wound, one sustained a penetrating abdominal wound, three sustained medium severity injuries and nine sustained minor injuries. There was neither on-scene nor in-hospital mortality among patients who were alive on arrival. The level of on-site care performed was basic life support in all cases. CONCLUSIONS: The results showed that TEMS integrated to daily EMS services including safe zone working only was a feasible, rapid and efficient way to provide medical support to law enforcement operations. PMID- 22092069 TI - Review of a Geriatric Health Literacy Workshop for Medical Students and Residents. AB - The "Geriatric Health Literacy Workshop for Medical Students and Residents" developed by Seema Limaye, MD, introduces medical students and residents to important concepts in communicating with older adults with low health literacy through a variety of teaching modalities. The workshop is available on the Portal of Geriatric Online Education (POGOe) and includes a didactic session, role playing exercises, and a critique of patient education handouts. A preworkshop health literacy module and postworkshop clinical observation sessions reinforce the workshop content. The activity is designed to take approximately 2.5 hours to administer to small groups of three to five learners and is also suitable for interdisciplinary teams of health professions trainees. This POGOe product review highlights important features of the workshop and suggests opportunities for improvement. PMID- 22092070 TI - Regional and temporal variability of the isotope composition (O, S) of atmospheric sulphate in the region of Freiberg, Germany, and consequences for dissolved sulphate in groundwater and river water. AB - The isotope composition of dissolved sulphate and strontium in atmospheric deposition, groundwater, mine water and river water in the region of Freiberg was investigated to better understand the fate of these components in the regional and global water cycle. Most of the isotope variations of dissolved sulphates in atmospheric deposition from three locations sampled bi- or tri-monthly can be explained by fractionation processes leading to lower [Formula: see text] (of about 2-30/00) and higher [Formula: see text] (of about 8-100/00) values in summer compared with the winter period. These samples showed a negative correlation between [Formula: see text] and [Formula: see text] values and a weak positive correlation between [Formula: see text] and [Formula: see text] values. They reflect the sulphate formed by aqueous oxidation from long-range transport in clouds. However, these isotope variations were superimposed by changes of the dominating atmospheric sulphate source. At two of the sampling points, large variations of mean annual [Formula: see text] values from atmospheric bulk deposition were recorded. From 2008 to 2009, the mean annual [Formula: see text] value increased by about 50/00; and decreased by about 40/00 from 2009 to 2010. A change in the dominating sulphate source or oxidation pathways of SO(2) in the atmosphere is proposed to cause these shifts. No changes were found in corresponding [Formula: see text] values. Groundwater, river water and some mine waters (where groundwater was the dominating sulphate source) also showed temporal shifts in their [Formula: see text] values corresponding to those of bulk atmospheric deposition, albeit to a lower degree. The mean transit time of atmospheric sulphur through the soil into the groundwater and river water was less than a year and therefore much shorter than previously suggested. Mining activities of about 800 years in the Freiberg region may have led to large subsurface areas with an enhanced groundwater flow along fractures and mined refilled ore lodes which may shorten transit times of sulphate from precipitation through groundwater into river water. PMID- 22092071 TI - Prospective validation of the modified mini nutritional assessment short-forms in the community, nursing home, and rehabilitation setting. AB - OBJECTIVES: To validate the modified Mini Nutritional Assessment (MNA) short forms (MNA-SFs) with respect to agreement with full MNA classification in the target populations of the MNA. DESIGN: Prospective analysis. SETTING: Community, nursing home, rehabilitation. PARTICIPANTS: Six hundred fifty-seven individuals aged 65 and older (75.3% female; mean age 82.3 +/- 7.4). MEASUREMENTS: Classification agreement between full MNA score and MNA-SF scores. RESULTS: Agreement between the full MNA and classification using the MNA-SFs was 84.6% when the MNA-SF using body mass index (BMI) was applied and 81.4% when the MNA-SF using calf circumference (CC) was applied. The highest agreement of classification was found in the community setting (90.8% and 90.4%, respectively) and the lowest in the rehabilitation setting (72.4% and 71.4%, respectively). Both MNA-SFs tended to underestimate nutritional status, but that was significant only for the MNA-SF with CC. CONCLUSION: The modified MNA-SFs represent a valuable tool for rapid and reliable nutritional screening. PMID- 22092072 TI - Fractionation of stigmasterol derivative and study of the effects of Celsia coromandelina aerial parts petroleum ether extract on appearance of puberty and ovarian steroidogenesis in immature mice. AB - CONTEXT: Celsia coromandelina Vahl (Scrophulariaceae) is a shrub found throughout Bangladesh and India, and it is distributed widely in the plains of West Bengal. It is used by the tribal people to treat diarrhea, dysentery, insomnia, skin eruption, fever, syphilis, helminthes infection, and to control fertility. OBJECTIVE: The objective of this study was to fractionate stigmasterol derivative and to investigate the effects of petroleum ether extract of C. coromandelina (PECC) aerial parts on the onset of reproductive maturity and the ovarian steroidogenesis in immature female mice. MATERIALS AND METHODS: PECC was prepared by hot extraction process and one compound was isolated by preparative TLC from it. PECC was completely freed from solvent and administered in immature female mice intraperitoneally once on every alternate day for nine doses. The sexual maturity was observed by means of vaginal opening, first estrus (days), rate of body growth, changes in weight of ovary, uterus and pituitary. The content of ascorbic acid, cholesterol, Delta5-3beta-hydroxy steroid dehydrogenase (Delta5 3beta-HSD) and glucose 6-phosphate dehydrogenase (G 6-PDH) activities in ovaries and carbonic anhydrase activity in uterus were measured by means of biochemical technique in control and treated mice. The activity of PECC was compared with standard marker compound ethinyl estradiol. RESULTS: The isolated compound was characterized as stigmasterol derivative. PECC treatment caused a remarkable delay (30.27 and 18.56%, respectively, by low dose) in sexual maturity compared to vehicle control as evidenced by the age of vaginal opening and appearance of first estrus (cornified smear). PECC treatment also caused a significant fall (58.6 and 50.0%, respectively, by low dose) in Delta5-3beta-HSD and G 6-PDH activities involved in ovarian steroidogenesis compared to vehicle control. Total cholesterol and ascorbic acid content in ovaries and carbonic anhydrase activity in uterus were increased significantly (low dose by 49.3, 424.6 and 82.4%, respectively) along with a reduction in the weight of ovary, uterus and pituitary in comparison to that of control. DISCUSSION AND CONCLUSION: Overall, these results demonstrate that PECC has a good antifertility effect and is responsible for the delayed development of sexual maturity, suppression of ovarian steroidogenesis and elevation of carbonic anhydrase activity in uterus of immature mice. This supports the claim by tribal people as a potential remedy for birth control. PMID- 22092073 TI - The pro-inflammatory effects of platelet contamination in plasma and mitigation strategies for avoidance. AB - BACKGROUND AND OBJECTIVES: Plasma and platelet concentrates are disproportionately implicated in transfusion-related acute lung injury (TRALI). Platelet-derived pro-inflammatory mediators, including soluble CD40 ligand (sCD40L), accumulate during storage. We hypothesized that platelet contamination induces sCD40L generation that causes neutrophil [polymorphonuclear leucocyte (PMN)] priming and PMN-mediated cytotoxicity. MATERIALS AND METHODS: Plasma was untreated, centrifuged (12,500 g) or separated from leucoreduced whole blood (WBLR) prior to freezing. Platelet counts and sCD40L concentrations were measured 1-5 days post-thaw. The plasma was assayed for PMN priming activity and was used in a two-event in vitro model of PMN-mediated human pulmonary microvascular endothelial cell (HMVEC) cytotoxicity. RESULTS: Untreated plasma contained 42+/ 4.2*10(3)/MUl platelets, which generated sCD40L accumulation (1.6-eight-fold vs. controls). Priming activity and HMVEC cytotoxicity were directly proportional to sCD40L concentration. WBLR and centrifugation reduced platelet and sCD40L contamination, abrogating the pro-inflammatory potential. CONCLUSION: Platelet contamination causes sCD40L accumulation in stored plasma that may contribute to TRALI. Platelet reduction is potentially the first TRALI mitigation effort in plasma manufacturing. PMID- 22092074 TI - Layered assemblies of a dialuminum-substituted silicotungstate trimer and the reversible interlayer cation-exchange properties. AB - Two polyoxometalate assemblies, TBA(9)[{gamma-H(2)SiW(10)O(36)Al(2)(MU-OH)(2)(MU OH)}(3)] (1; TBA = tetra-n-butylammonium) and TBA(6)Li(3)[{gamma H(2)SiW(10)O(36)Al(2)(MU-OH)(2)(MU-OH)}(3)].18H(2)O (2), were synthesized by trimerization of a dialuminum-substituted silicotungstate monomer. Both 1 and 2 possessed a layered structure composed of a basal sheet unit [TBA(3){gamma H(2)SiW(10)O(36)Al(2)(MU-OH)(2)(MU-OH)}(3)](6-) and interlayer cations. The interconversion between 1 and 2 reversibly took place through interlayer cation exchange. PMID- 22092075 TI - Identification of phosphoproteins in Arabidopsis thaliana leaves using polyethylene glycol fractionation, immobilized metal-ion affinity chromatography, two-dimensional gel electrophoresis and mass spectrometry. AB - Reversible protein phosphorylation is a key regulatory mechanism in cells. Identification and characterization of phosphoproteins requires specialized enrichment methods, due to the relatively low abundance of these proteins, and is further complicated in plants by the high abundance of Rubisco in green tissues. We present a novel method for plant phosphoproteome analysis that depletes Rubisco using polyethylene glycol fractionation and utilizes immobilized metal ion affinity chromatography to enrich phosphoproteins. Subsequent protein separation by one- and two-dimensional gel electrophoresis is further improved by extracting the PEG-fractionated protein samples with SDS/phenol and methanol/chloroform to remove interfering compounds. Using this approach, we identified 132 phosphorylated proteins in a partial Arabidopsis leaf extract. These proteins are involved in a range of biological processes, including CO(2) fixation, protein assembly and folding, stress response, redox regulation, and cellular metabolism. Both large and small subunits of Rubisco were phosphorylated at multiple sites, and depletion of Rubisco enhanced detection of less abundant phosphoproteins, including those associated with state transitions between photosystems I and II. The discovery of a phosphorylated form of AtGRP7, a self regulating RNA-binding protein that affects floral transition, as well as several previously uncharacterized ribosomal proteins confirm the utility of this approach for phosphoproteome analysis and its potential to increase our understanding of growth and development in plants. PMID- 22092076 TI - A regional meeting continues to grow: the 2nd annual Michigan alliance for Reproductive Technologies and Science Conference. PMID- 22092077 TI - Interchromosomal effect analyses by sperm FISH: incidence and distribution among reorganization carriers. AB - Structural reorganization carriers usually present compromised fertility accompanied by an increased risk of producing gametes with chromosomal abnormalities that can be transmitted to the offspring. In part these imbalances are ascribed to result from the occurrence of meiotic disturbances produced by the rearrangements in the proper segregation of other chromosome pairs. This phenomenon of interference has been called interchromosomal effect (ICE). Several studies have been performed to assess the occurrence of ICE in structural reorganization carriers by analyzing the frequencies of numerical abnormalities in the gametes. Nevertheless, the occurrence and distribution of these disturbing events still is a controversial issue. In this work we present compiled data from 130 sperm fluorescent in situ hybridization (FISH) studies performed in carriers of the most frequent structural rearrangements in humans: 44 Robertsonian translocations, 66 reciprocal translocations and 13 inversions. Data from 7 complex/multiple rearrangements will be considered in a separate group. Significant increases of gametes with numerical abnormalities have been detected in all types of reorganization carriers. Among the groups of non-complex/multiple rearrangements, Robertsonian translocations appear to be the most prone to produce such interference (54.5%) closely followed by reciprocal translocations (43.9%). In contrast, ICE's were only detected in 7.7% of the inversion carriers analyzed. The presence of complex/multiple rearrangements seems to be an important factor for promoting ICE, as 71.4% of these carriers presented increased rates of gametes with numerical abnormalities. Altogether, almost half of the structural reorganization carriers (45.4%) present a higher reproductive risk of producing aneuploid/diploid spermatozoa compared to the general population. This high incidence has been obtained by analyzing a small set of chromosomes, suggesting that underlying meiotic disorders could be present in these individuals. Further ICE studies in structural reorganization carriers will help to clarify the still unknown predisposing cytogenetic features that promote this phenomenon. PMID- 22092078 TI - The cerebellum, cognition, and behaviour. PMID- 22092079 TI - Verification of the Robin and Graham classification system of hip disease in cerebral palsy using three-dimensional computed tomography. AB - AIM: We evaluated the validity of the Robin and Graham classification system of hip disease in cerebral palsy (CP) using three-dimensional computed tomography in young people with CP. METHOD: A total of 91 hips in 91 consecutive children with bilateral spastic CP (57 males, 34 females; nine classified at Gross Motor Function Classification System level II, 42 at level III, 32 at level IV, and eight at level V; mean age 5 y 2 mo, SD 11 mo; range 2-6 y) were investigated retrospectively using anteroposterior plain radiographs and three-dimensional computed tomography (3D-CT) of the hip. The migration percentage was calculated on plain radiographs and all participants were classified into four groups according to migration percentage: grade II, migration percentage >= 10% but <= 15%, (four hips), grade III, migration percentage >15% but <= 30%, (20 hips); grade IV, migration percentage >30% but <100%, (63 hips); and grade V, migration percentage >= 100%, (four hips). The lateral opening angle and the sagittal inclination angle of the acetabulum, the neck-shaft angle, and the femoral anteversion of the femur were measured on 3D-CT. RESULTS: The three-dimensional quantitative evaluation indicated that there were significant differences in the lateral opening angle and the neck-shaft angle between the four groups (Kruskal Wallis test, p <= 0.001). INTERPRETATION: This three-dimensional evaluation supports the validation of the Robin and Graham classification system for hip disease in 2- to 7-year-olds with CP. PMID- 22092081 TI - Development of a standardized low-dose double-blind placebo-controlled challenge vehicle for the EuroPrevall project. AB - BACKGROUND: Double-blind placebo-controlled food challenge (DBPCFC) is the gold standard for diagnosing food allergy. Standardized materials and protocols are essential for comparing DBPCFC results for multicentre studies such as EuroPrevall. This required the development and piloting of a standardized vehicle and low-dose protocol for confirming food allergy and determination of minimum eliciting doses (MEDs). METHODS: A low-dose DBPCFC protocol was developed, with eight titrated protein doses from 3 MUg to 1 g. This was delivered using a simple, microbiologically stable food base incorporating allergenic food ingredients manufactured at three sites and centrally distributed to clinical centres. Allergen blinding was assessed by a professional sensory testing panel using a triangle test. Homogeneity and allergen content were confirmed by ELISA and clinical efficacy was assessed in a pilot study, using celeriac and hazelnut as exemplars. RESULTS: Celeriac and hazelnut ingredients were sufficiently blinded in the dessert. The dessert meals were successfully piloted with hazelnut in allergy clinics in Spain, the Netherlands and Italy and with celeriac and hazelnut in Zurich. The challenges elicited a range of subjective and objective reactions ranging in severity from mild itching of the oral mucosa to bronchospasm. CONCLUSIONS: A standardized challenge vehicle proven to sufficiently blind processed, powdered hazelnut and celeriac ingredients and that can be reproducibly manufactured has been developed. This pilot study shows that the vehicle is promising for the confirmation of food allergy and determination of MEDs in adults and children with body weight >28.8 kg (approximately 7-11 years old). PMID- 22092080 TI - Behavioural comorbidity in Tanzanian children with epilepsy: a community-based case-control study. AB - AIM: The aim of this study was to define the prevalence of and risk factors for behavioural disorders in children with epilepsy from a rural district of Tanzania by conducting a community-based case-control study. METHOD: One hundred and twelve children aged 6 to 14 years (55 males, 57 females; median age 12 y) with active epilepsy (at least two unprovoked seizures in the last 5 y) were identified in a cross-sectional survey and included in this study. Children who were younger than 6 years were excluded in order to eliminate febrile seizures. Behaviour was assessed using the Rutter scale; children who scored 13 or more were considered to have disordered behaviour. A comparison group was made up of age- and sex-matched children without epilepsy (n = 113; 57 males, 56 females; median age 12 y). RESULTS: Behavioural disorders were diagnosed in 68 of 103 (66%) children with epilepsy and in 19 of 99 (19%) controls. Disordered behaviour was significantly more common in children with epilepsy than in the comparison group (univariate odds ratio 8.2; 95% confidence interval [CI] 4.3-15.6; p < 0.001) and frequent seizures and poor scholastic attainment were associated in children with epilepsy. Behavioural disorders were not associated with antiepileptic drug usage. Attention problems were present in 48 of 91 (53%) children with epilepsy and 16 of 97 (17%) controls (univariate odds ratio 5.7; 95% CI 2.9-11.1; p < 0.001). In children with epilepsy, attention problems were significantly more common in males and were associated with frequent seizures. INTERPRETATION: Children with epilepsy in a rural area of sub-Saharan Africa have a high prevalence of behavioural disorders and attention problems, both of which are associated with frequent seizures. Providing behaviour assessment and appropriate intervention programmes for children with epilepsy may reduce the burden of behaviour disorders in this setting. PMID- 22092083 TI - Powder X-ray diffraction method for the quantification of cocrystals in the crystallization mixture. AB - CONTEXT: The solid state purity of cocrystals critically affects their performance. Thus, it is important to accurately quantify the purity of cocrystals in the final crystallization product. OBJECTIVE: The aim of this study was to develop a powder X-ray diffraction (PXRD) quantification method for investigating the purity of cocrystals. The method developed was employed to study the formation of indomethacin-saccharin (IND-SAC) cocrystals by mechanochemical methods. MATERIALS AND METHODS: Pure IND-SAC cocrystals were geometrically mixed with 1:1 w/w mixture of indomethacin/saccharin in various proportions. An accurately measured amount (550 mg) of the mixture was used for the PXRD measurements. The most intense, non-overlapping, characteristic diffraction peak of IND-SAC was used to construct the calibration curve in the range 0-100% (w/w). This calibration model was validated and used to monitor the formation of IND-SAC cocrystals by liquid-assisted grinding (LAG). RESULTS: The IND-SAC cocrystal calibration curve showed excellent linearity (R(2) = 0.9996) over the entire concentration range, displaying limit of detection (LOD) and limit of quantification (LOQ) values of 1.23% (w/w) and 3.74% (w/w), respectively. Validation results showed excellent correlations between actual and predicted concentrations of IND-SAC cocrystals (R(2) = 0.9981). DISCUSSION: The accuracy and reliability of the PXRD quantification method depend on the methods of sample preparation and handling. The crystallinity of the IND-SAC cocrystals was higher when larger amounts of methanol were used in the LAG method. CONCLUSION: The PXRD quantification method is suitable and reliable for verifying the purity of cocrystals in the final crystallization product. PMID- 22092082 TI - The health care cost implications of overweight and obesity during childhood. AB - OBJECTIVE: To investigate whether childhood overweight at age 4-5 increases publicly funded health care costs during childhood, and to explore the role of timing and duration of overweight on health costs. DATA SOURCES: The Longitudinal Study of Australian Children (2004-2008) and linked records from Medicare, Australia's public health insurance provider (2004-2009). STUDY DESIGN: The influence of overweight status on non-hospital Medicare costs incurred by children over a 5-year period was estimated using two-part models and one-part generalized linear models (GLM). All models controlled for demographic, socioeconomic, and parental characteristics. PRINCIPAL FINDINGS: Being overweight at age 4-5 is associated with significantly higher pharmaceutical and medical care costs. The results imply that for all children aged 4 and 5 in 2004-2005, those who were overweight had a combined 5-year Medicare bill that was AUD$9.8 million higher than that of normal weight children. Results from dynamic analyses show that costs of childhood overweight occur contemporaneously, and the duration of overweight is positively associated with medical costs for children who became overweight after age 5. CONCLUSIONS: This study reveals that the financial burden to the public health system of childhood overweight and obesity occurs even during the first 5 years of primary school. PMID- 22092084 TI - Oral malodorous compound causes caspase-8 and -9 mediated programmed cell death in osteoblasts. AB - BACKGROUND AND OBJECTIVE: Hydrogen sulfide (H(2) S) is one of two volatile sulfur compounds that are known to be the main cause of oral malodor; the other is methyl mercaptan. Other known volatiles existing in mouth air do not contribute significantly to oral malodor originating in the oral cavity. Hydrogen sulfide is also known to be an etiological factor in periodontal disease. However, the effects of H(2) S on alveolar bone remain unclear. The objectives of this study were to determine the apoptotic effects of H(2) S on osteoblasts and to verify the apoptotic molecular pathways. MATERIAL AND METHODS: A clonal murine calvaria cell line was incubated with 50 ng/mL of H(2) S. To detect apoptosis, the cells were analysed by flow cytometry and ELISA. Mitochondrial membrane depolarization was assessed using flow cytometry as well. ELISA was used to evaluate the release of cytochrome c into the cytosol and to assess Fas ligand, p53, tumor necrosis factor alpha, interleukin IL1-alpha IL-beta, IL-2, IL-4, IL-10, interferon-gamma, granulocyte-colony stimulating factor and granulocyte-macrophage colony stimulating factor. Caspase-3, -8 and -9 activities were estimated. Expression of BAX and Bcl-2 was assessed by real-time quantitative RT-PCR. DNA fragmentation was detected by single-cell gel electrophoresis. Fas receptors were evaluated by western blotting. RESULTS: After H(2) S incubation, apoptotic levels increased significantly in a time-dependent manner. Mitochondrial membrane depolarization, the release of cytochrome c, p53 and caspase-3, -8 and -9 and DNA fragmentation were all significantly greater. BAX gene activity was upregulated, whereas Bcl-2 remained low. Fas ligand/Fas receptor, tumor necrosis factor alpha and other cytokines were not increased to a significant degree. CONCLUSION: At less-than pathological concentrations in gingival crevicular fluid, H(2) S induces apoptosis in osteoblasts. The molecular mechanisms underlying the apoptotic process include p53, a mitochondrial pathway and caspase-8 activation. PMID- 22092085 TI - Characterization of four new HLA alleles: HLA-B*15:01:18, HLA-B*44:110, HLA C*04:01:22 and HLA-DQB 1*05:14. AB - We describe four novel HLA alleles, HLA-B*15:01:18, HLA-B*44:110, HLA-C*04:01:22 and HLA-DQB1*05:14. PMID- 22092086 TI - Stereoselective total synthesis of (+/-)-peribysin E. AB - Radical cyclization of iodoketone 3 afforded cis-hydrindanone 8. Compound 8 was converted into key intermediate 5 via conventional transformations. Annulation of a spiro-lactal unit to 5 was pursued with three different approaches. In the first approach, radical cyclization of propargyl ester 17 provided spiro-lactone 18 with an undesired stereochemistry. Attempts to invert the stereochemistry at the spiro-center via retro-aldol and aldol condensation of compound 20 failed. In the second approach, key intermediate 5 was transformed into 23. Acylation of compound 23 gave 24 as a single diastereomer with the desired stereochemistry but in low yield. NBS bromination of 24 followed by lactone formation gave 26 in low yield. Alternatively, allylic oxidation of 24 with SeO(2) followed by lactonization gave 26 also in low yield. Finally, a third approach employing a semipinacol-type rearrangement of epoxy-alcohol 33 gave aldehyde 34 with the desired stereochemistry. Treatment of compound 34 with HCl in MeOH effected spiro lactal formation and provided (+/-)-peribysin E. The overall yield of our synthesis is 3.2% from 2-methylcyclohenen-1-one. PMID- 22092087 TI - Toward a tripartite model of intrinsic motivation. AB - Intrinsic motivation (IM) refers to engaging in an activity for the pleasure inherent in the activity. The present article presents a tripartite model of IM consisting of IM to know (i.e., engaging in an activity to experience pleasure while learning and trying to understand something new), IM toward accomplishment (i.e., engaging in an activity for the pleasure experienced when attempting task mastery), and IM to experience stimulation (i.e., engaging in an activity for feelings of sensory pleasure). The tripartite model of IM posits that each type of IM can result from task, situational, and personality determinants and can lead to specific types of cognitive, affective, and behavioral outcomes. The purpose of this research was to test some predictions derived from this model. Across 4 studies (Study 1: N = 331; Study 2: N = 113; Study 3: N = 58; Study 4: N = 135), the 3 types of IM as well as potential determinants and consequences were assessed. Results revealed that experiencing one type of IM over the others depends in part on people's personality styles. Also, each type of IM was found to predict specific outcomes (i.e., affective states and behavioral choices). The implications of the tripartite model of IM for motivation research are discussed. PMID- 22092094 TI - Nanoporous carbohydrate metal-organic frameworks. AB - The binding of alkali and alkaline earth metal cations by macrocyclic and diazamacrobicyclic polyethers, composed of ordered arrays of hard oxygen (and nitrogen) donor atoms, underpinned the development of host-guest supramolecular chemistry in the 1970s and 1980s. The arrangement of -OCCO- and -OCCN- chelating units in these preorganized receptors, including, but not limited to, crown ethers and cryptands, is responsible for the very high binding constants observed for their complexes with Group IA and IIA cations. The cyclodextrins (CDs), cyclic oligosaccharides derived microbiologically from starch, also display this OCCO- bidentate motif on both their primary and secondary faces. The self assembly, in aqueous alcohol, of infinite networks of extended structures, which have been termed CD-MOFs, wherein gamma-cyclodextrin (gamma-CD) is linked by coordination to Group IA and IIA metal cations to form metal-organic frameworks (MOFs), is reported. CD-MOF-1 and CD-MOF-2, prepared on the gram-scale from KOH and RbOH, respectively, form body-centered cubic arrangements of (gamma-CD)(6) cubes linked by eight-coordinate alkali metal cations. These cubic CD-MOFs are (i) stable to the removal of solvents, (ii) permanently porous, with surface areas of ~1200 m(2) g(-1), and (iii) capable of storing gases and small molecules within their pores. The fact that the -OCCO- moieties of gamma-CD are not prearranged in a manner conducive to encapsulating single metal cations has led to our isolating other infinite frameworks, with different topologies, from salts of Na(+), Cs(+), and Sr(2+). This lack of preorganization is expressed emphatically in the case of Cs(+), where two polymorphs assemble under identical conditions. CD-MOF-3 has the cubic topology observed for CD-MOFs 1 and 2, while CD-MOF-4 displays a channel structure wherein gamma-CD tori are perfectly stacked in one dimension in a manner reminiscent of the structures of some gamma-CD solvates, but with added crystal stability imparted by metal-ion coordination. These new MOFs demonstrate that the CDs can indeed function as ligands for alkali and alkaline earth metal cations in a manner similar to that found with crown ethers. These inexpensive, green, nanoporous materials exhibit absorption properties which make them realistic candidates for commercial development, not least of all because edible derivatives, fit for human consumption, can be prepared entirely from food-grade ingredients. PMID- 22092095 TI - Physical exercise performed before bedtime improves the sleep pattern of healthy young good sleepers. AB - To investigate the influence of different intensities and durations of exercise before bedtime on the sleep pattern and core body temperature of individuals considered good sleepers, we selected 17 healthy males and all underwent 5 nonconsecutive days of study. Measurements of polysomnographic parameters and core body temperature were taken at baseline and after each experimental protocol, performed at night. We found increased sleep efficiency (p = .016) among all protocols compared with baseline data and increase in REM sleep latency (p = .047) between two experiments; there was decrease in the percentage of stage 1 sleep (p = .046) and wake after sleep onset (p = .003). Core body temperature did not change significantly during the nights following exercise. Exercise performed before sleep does not impair sleep quality; rather, its practice improves sleep in good sleepers who are nonathletes, and may be considered to improve sleep pattern. PMID- 22092096 TI - Intraoperative contamination of the suction tip in clean orthopedic surgeries in dogs and cats. AB - OBJECTIVE: To (1) determine suction tip (intermittent and continuous mode) contamination rate in orthopedic surgery in dogs and cats; (2) examine the effect of surgical time on contamination; and (3) report bacteria isolated. STUDY DESIGN: Clinical study. SAMPLE POPULATION: Clean orthopedic surgeries (n = 50). METHODS: Surgical procedures were assigned to 1 of 2 groups: (1) continuous (n = 25) or (2) intermittent suction (n = 25). A control suction was operated in each surgery. Samples for aerobic and anaerobic bacteriologic examination were collected from the surgical suction at 0, 20, 60 minutes, and at the end of surgery, and from the control suction at the end of the surgery only. Comparison of continuous and intermittent suction data, and the effect of surgical time on contamination rate were analyzed using a Kaplan-Meier survival analysis followed by a Cox proportional hazards model. P < .05 was considered significant. RESULTS: Aerobic contamination occurred in 22 of 50 surgical procedures and there was no anaerobic growth. There was no significant difference between continuous and intermittent suction mode groups (P = .40). Surgical time did not influence the contamination rate (P = .79). Bacterial cultures mainly revealed coagulase negative Staphylococci, however multiresistant bacteria were isolated. CONCLUSIONS: We failed to find superiority of the intermittent operation mode of the suction tip over the continuous mode. A safe time frame before contamination of the suction tip occurs that could not be defined. PMID- 22092097 TI - A randomized trial on elderly laypersons' CPR performance in a realistic cardiac arrest simulation. AB - BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is important for survival after cardiac arrest. We hypothesized that elderly laypersons would perform CPR poorer in a realistic cardiac arrest simulation, compared to a traditional test. METHODS: Sixty-four lay rescuers aged 50-75 were randomized to realistic or traditional test, both with ten minutes of telephone assisted CPR. Realistic simulation started suddenly without warning, leaving the test subject alone in a confined and noisy apartment. Traditional test was conducted in a spacious and calm classroom with a researcher present. CPR performance was recorded with a manikin with human like chest properties. Heart rate and self reported exhaustion were registered. RESULTS: CPR quality was not different in the two groups: compression depth, 43 mm +/- 7 versus 43 +/- 4, P = 0.72; compressions rate, 97 min(-1) +/- 11 versus 93 +/- 15, P = 0.26; ventilation rate, 2.4 min(-1) +/- 1.7 versus 2.8 +/- 1.1, P = 0.35; and hands-off time 273 s +/- 50 versus 270 +/- 66, P = 0.82; in realistic (n = 31) and traditional (n = 33) groups, respectively. No fatigue was evident in the repeated measures analysis of variance. Work load was not different between the groups; attained percentage of age predicted maximum heart rate, 73% +/- 9 and 76 +/- 11, P = 0.37, reported exhaustion 43 +/- 21 (scale: 0 to 100) and 37 +/- 19, P = 0.24. CONCLUSIONS: Elderly lay people are capable of performing chest compressions with acceptable quality for ten minutes in a realistic cardiac arrest simulation. Ventilation quality and hands-off time were not adequate in either group. PMID- 22092088 TI - Signals and regulators that govern Streptomyces development. AB - Streptomyces coelicolor is the genetically best characterized species of a populous genus belonging to the gram-positive Actinobacteria. Streptomycetes are filamentous soil organisms, well known for the production of a plethora of biologically active secondary metabolic compounds. The Streptomyces developmental life cycle is uniquely complex and involves coordinated multicellular development with both physiological and morphological differentiation of several cell types, culminating in the production of secondary metabolites and dispersal of mature spores. This review presents a current appreciation of the signaling mechanisms used to orchestrate the decision to undergo morphological differentiation, and the regulators and regulatory networks that direct the intriguing development of multigenomic hyphae first to form specialized aerial hyphae and then to convert them into chains of dormant spores. This current view of S. coelicolor development is destined for rapid evolution as data from '-omics' studies shed light on gene regulatory networks, new genetic screens identify hitherto unknown players, and the resolution of our insights into the underlying cell biological processes steadily improve. PMID- 22092098 TI - Formation of ripples in graphene as a result of interfacial instabilities. AB - Formation of ripples on a supported graphene sheet involves interfacial interaction with the substrate. In this work, graphene was grown on a copper foil by chemical vapor deposition from methane. On thermal quenching from elevated temperatures, we observed the formation of ripples in grown graphene, developing a peculiar topographic pattern in the form of wavy grooves and single/double rolls, roughly honeycomb cells, or their combinations. Studies on pure copper foil under corresponding conditions but without the presence of hydrocarbon revealed the appearance of peculiar patterns on the foil surface, such as dendritic structures that are distinctive not of equilibrium solidified phases but arise from planar and/or convective instabilities driven by solutal and thermal capillary forces. We propose a new origin for the formation of ripples in the course of graphene growth at elevated temperatures, where the topographic pattern formation is governed by dynamic instabilities on the interface of a carbon-catalyst binary system. These non-equilibrium processes can be described based on Mullins-Sekerka and Benard-Marangoni instabilities in diluted binary alloys, which offer control over the ripple texturing through synthesis parameters such as temperature, imposed temperature gradient, quenching rate, diffusion coefficients of carbon in the metal catalyst, and the miscibility gap of the metal catalyst-carbon system. PMID- 22092100 TI - First magnetostructural study on a heterodinuclear 2,2'-bipyrimidine-bridged complex. AB - The use of the [ReCl(4)(bpym)] precursor as a ligand toward the fully solvated nickel(II) metal ion affords the first example of a 2,2'-bipyrimidine-bridged Re(IV)-Ni(II) complex, [ReCl(4)(MU-bpym)NiBr(2)(H(2)O)(2)] (1), whose intramolecular ferromagnetic coupling has been substantiated from both experimental and theoretical studies. PMID- 22092099 TI - Psychotropic medication burden and factors associated with antipsychotic use: an analysis of a population-based sample of community-dwelling older persons with dementia. AB - OBJECTIVES: To estimate the proportion of community-dwelling older adults with dementia being prescribed a psychotropic and to identify patient and caregiver factors associated with antipsychotic use. METHODS: Retrospective cohort study of the Aging, Demographics, and Memory Study (ADAMS) from 2002 to 2004 designed to assess dementia severity and service use of community-dwelling older adults. The frequency of psychotropic medication (antipsychotics, antidepressants, anticonvulsants, and benzodiazepines) use was tabulated and weighted to the U.S. population according to dementia diagnosis. Logistic regression analysis identified factors associated with antipsychotic use. RESULTS: The 307 ADAMS participants had the following dementia diagnoses: Alzheimer's disease (69.3%), vascular dementia (17.7%), and other dementia (12.4%). The proportion of participants prescribed a psychotropic medication broken down according to therapeutic class was 19.1% antipsychotics, 29.1% antidepressants, 9.8% benzodiazepines, and 8.8% anticonvulsants. Older adults with dementia were significantly more likely to receive an antipsychotic if they had moderate (odds ratio (OR) = 7.4, P = .002) or severe (OR = 5.80, P = .002) dementia than if they had mild dementia or were diagnosed with Alzheimer's disease (OR = 6.7, P = .04) compared to vascular dementia. Older adults with dementia who lived with a caregiver were significantly less likely to taking an antipsychotic (OR = 0.19, P = .001) than those who lived alone. Also, persons with dementia were significantly less likely to be prescribed an antipsychotic if their caregiver was clinically depressed (OR = 0.03, P = .005) than if their caregiver was not depressed. CONCLUSION: Psychotropic medication use is common in community dwelling older adults with dementia. Caregivers appear to have a substantial effect on whether an antipsychotic is prescribed, which adds additional complexity to conversations discussing the risk:benefit ratio of this medication class. PMID- 22092101 TI - Radioactivity of sand, groundwater and wild plants in northeast Sinai, Egypt. AB - The radioactivity levels are poorly studied in non-coastal arid regions. For this reason, 38 locations covering an area of about 350 km(2) in northeast Sinai, Egypt, were investigated by gamma-ray spectroscopy. Moderately significant correlations among (238)U, (234)Th, and (226)Ra isotopes and low significant correlations between the concentrations of (238)U-series and (232)Th in sand were obtained. No evidence of correlation was found between the concentrations of radioisotopes and pH, grain size, total organic matter content, bicarbonate or calcium carbonate concentrations of the sand samples. The mean values of soil-to plant transfer factor were 0.15, 0.18, 1.52 and 0.74 for (226)Ra, (232)Th, (40)K, and (137)Cs, respectively. The range of concentrations of (226)Ra,( 232)Th, and (40)K in water samples collected from five wells were<0.4-0.16,<0.4-0.13, and<0.15-1.62 Bq l(-1), respectively. The mean absorbed dose rate in outdoor air at a height of 1 m above the ground surface for the sand samples was 19.4 nGy h( 1). The Ra(eq) activities of the sands are lower than the recommended maximum value of 370 Bq kg(-1) criterion limit for building materials. PMID- 22092103 TI - Self-generated retrievals while multitasking improve memory for names. AB - We used a translational research paradigm to investigate whether distributed retrievals could benefit name learning in social situations. Undergraduates (N=64) were trained to generate distributed retrievals while they were multitasking. Students learned to generate distributed retrievals according to either an expanding or a uniform schedule. Their self-generated distributed retrievals while they were multitasking were effective in improving name recall for both retrieval schedules. The increase with self-generated retrievals while multitasking was greater (eta2 =.76) than the increase that Helder and Shaughnessy ( 2008 ) found with experimenter-controlled retrievals while multitasking (eta2 =.42). These findings provide evidence that the beneficial effect of distributed retrievals can extend to learning names in a social situation. PMID- 22092102 TI - Angiotensin-converting enzyme inhibitor and statin use and incident mobility limitation in community-dwelling older adults: the Health, Aging and Body Composition study. AB - OBJECTIVES: To evaluate whether the use of angiotensin-converting enzyme (ACE) inhibitors and statins is associated with a lower risk of incident mobility limitation in older community dwelling adults. DESIGN: Longitudinal cohort study. SETTING: Health, Aging and Body Composition (Health ABC) study. PARTICIPANTS: Three thousand fifty-five participants who were well functioning at baseline (no mobility limitations). MEASUREMENTS: Summated standardized daily doses (low, medium, high) and duration of ACE inhibitor and statin use were computed. Mobility limitation (two consecutive self-reports of having any difficulty walking one-quarter of a mile or climbing 10 steps without resting) was assessed every 6 months after baseline. Multivariable Cox proportional hazards analyses were conducted, adjusting for demographics, health status, and health behaviors. RESULTS: At baseline, 15.2% used ACE inhibitors and 12.9% used statins; use of both was greater than 25% by Year 6. Over 6.5 years of follow-up, 49.8% had developed mobility limitation. In separate multivariable models, neither ACE inhibitor (multivariate hazard ratio (HR) = 0.95, 95% confidence interval (CI) = 0.82-1.09) nor statin use (multivariate HR = 1.02, 95% CI = 0.87-1.17) was associated with lower risk of mobility limitation. Similar findings were seen in analyses examining dose-response and duration-response relationships and a sensitivity analysis restricted to those with hypertension. CONCLUSION: ACE inhibitors and statins widely prescribed to treat hypertension and hypercholesterolemia, respectively, do not lower risk of mobility limitation, an important indicator of quality of life. PMID- 22092104 TI - The relation of the conceptual self to recent and distant autobiographical memories. AB - Based on the self-memory system model (SMS; Conway, Singer, & Tagini, 2004) of autobiographical memory, this study uses a large sample of young and middle-aged adults to investigate the relation between individuals' current self characteristics and the content of both their earliest childhood memory and a recent memory. In the first session, participants' current self-characteristics were assessed. In the second session, individuals provided a written narrative of their earliest childhood memory and a more recent memory (within-participants design) and rated the self themes present in each memory. In keeping with the SMS model, findings show that current self-characteristics were reflected in individuals' memories. As predicted, however, recent memories were more frequently linked to current self-characteristics than were earliest memories. All six current self-characteristics predicted the inclusion of these themes in recent memories, but only four self-characteristics were associated with memory themes in earliest memories. The relation between current self-characteristics and memory themes did not differ across young and middle-aged adults, suggesting developmental stability in these relations. Findings provide general support for the SMS model but also suggest possibilities for its extension and refinement. PMID- 22092105 TI - Directed forgetting of autobiographical memory in mild Alzheimer's disease. AB - Using the autobiographical directed forgetting method (Barnier et al., 2007), the present paper addressed the intentional inhibitory processes of episodic and semantic autobiographical memory in Alzheimer's disease (AD). Mild AD patients and healthy elderly people were instructed to either forget or to continue remembering previously generated autobiographical events. In a later recall test they were asked to reconstruct the early-generated memories regardless of the forget/remember instruction. Autobiographical reconstruction was further distributed into episodic and semantic memories. Results showed no forget instruction effect on episodic or semantic autobiographical recall with AD patients, whereas healthy elderly people were able to inhibit only episodic autobiographical memories. The findings suggest an impairment of the intentional inhibitory processes in autobiographical memory with AD and a relative preservation of these mechanisms with normal ageing. They also demonstrate an earlier decline in the intentional inhibitory processes compared to the autobiographical deterioration in AD. PMID- 22092106 TI - Memory for details with self-referencing. AB - Self-referencing benefits item memory, but little is known about the ways in which referencing the self affects memory for details. Experiment 1 assessed whether the effects of self-referencing operate only at the item, or general, level or whether they also enhance memory for specific visual details of objects. Participants incidentally encoded objects by making judgements in reference to the self, a close other (one's mother), or a familiar other (Bill Clinton). Results indicate that referencing the self or a close other enhances both specific and general memory. Experiments 2 and 3 assessed verbal memory for source in a task that relied on distinguishing between different mental operations (internal sources). The results indicate that self-referencing disproportionately enhances source memory, relative to conditions referencing other people, semantic, or perceptual information. We conclude that self referencing not only enhances specific memory for both visual and verbal information, but can also disproportionately improve memory for specific internal source details. PMID- 22092109 TI - Impact of solvent/detergent treatment of plasma on transfusion-relevant bacteria. AB - BACKGROUND: A solvent/detergent (S/D) treatment in a medical device has been developed for pathogen reduction of plasma for transfusion. Impact of S/D on bacterial growth and on the capacity of complement to kill bacteria has been investigated in this study. STUDY DESIGN AND METHODS: A pool of apheresis plasma from four donors was spiked with eight transfusion-relevant bacteria. Plasma was treated with 1% tri(n-butyl) phosphate and 1% Triton X-45 at 31 degrees C for 90 min and then extracted by oil at 31 degrees C for 70 min. Decomplemented plasma and Phosphate Buffer Saline were used as controls. Bacterial count was determined in samples taken immediately after spiking, or after S/D and oil treatment. Similar experiments were conducted using three individual recovered plasma donations. Bacteria growth inhibition tests were performed using discs soaked with plasma samples whether containing the S/D agents or not. RESULTS: The mean reduction factors of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae due to complement during S/D treatment were >8.75, 4.71, and 4.18 log in pooled plasma and >7.42, 2.24 and >6.08 log in individual plasmas, respectively. Bacillus cereus and Bacillus subtilis were inactivated by S/D (>7.04 and 1.60 log in pooled, and >6.06 and 2.39 in individual plasmas, respectively). Staphylococcus aureus, Staphylococcus epidermidis and Enterobacter cloacae did not multiply during S/D treatment of plasma. Growth inhibition tests revealed an inhibition of three gram-negative bacteria by complement and all gram positive by S/D. CONCLUSION: The S/D treatment of plasma does not alter the bactericidal activity of complement, and inactivates some gram-positive bacteria. PMID- 22092110 TI - Predictors of postpartum weight change among overweight and obese women: results from the Active Mothers Postpartum study. AB - BACKGROUND: The postpartum period may be critical for the development of midlife obesity. Identifying factors associated with postpartum weight change could aid in targeting women for healthy lifestyle interventions. METHODS: Data from Active Mothers Postpartum (AMP), a study of overweight and obese postpartum women (n=450), were analyzed to determine the effect of baseline characteristics, breastfeeding, diet, physical activity, and contraception on weight change from 6 weeks to 12, 18, and 24 months postpartum. The repeated measures mixed model was used to test the association of these effects with weight change. RESULTS: Although mean weight loss was modest (0.49 kg by 24 months), the range of weight change was striking (+21.5 kg to -24.5 kg, standard deviation [SD] 7.4). Controlling only for baseline weight, weight loss was associated with breastfeeding, hormonal contraception, lower junk food and greater healthy food intake, and greater physical activity. Only junk food intake and physical activity were significant after controlling for all other predictors. CONCLUSIONS: Eating less healthy foods and being less physically active put overweight and obese women at risk of gaining more weight after a pregnancy. PMID- 22092111 TI - Overexpression of ADK in human astrocytic tumors and peritumoral tissue is related to tumor-associated epilepsy. AB - PURPOSE: Adenosine kinase (ADK), a largely astrocyte-based metabolic enzyme, regulates adenosine homeostasis in the brain. Overexpression of ADK decreases extracellular adenosine and consequently leads to seizures. We hypothesized that dysfunction in the metabolism of tumor astrocytes is related to changes in ADK expression and that those changes might be associated with the development of epilepsy in patients with tumors. METHODS: We compared ADK expression and cellular distribution in surgically removed tumor tissue (n = 45) and peritumoral cortex (n = 20) of patients with glial and glioneuronal tumors to normal control tissue obtained at autopsy (n = 11). In addition, we compared ADK expression in tumor patients with and without epilepsy. To investigate ADK expression, we used immunohistochemistry and Western blot analysis. ADK activity measurement was performed in surgical specimens of astrocytomas World Health Organization (WHO) grade III (n = 3), peritumoral cortex (n = 3), and nonepileptic cortex (n = 3). KEY FINDINGS: Immunohistochemistry predominantly showed cytoplasmic labeling in tumors and peritumoral tissue containing infiltrating tumor cells. ADK immunoreactivity was significantly stronger in tumor and peritumoral tissue compared to normal white matter and normal cortex, especially in astrocytoma WHO grade III, as confirmed by Western blot analysis and ADK activity measurements. Importantly, we found a significantly higher expression of ADK in the peritumoral infiltrated tissue of patients with epilepsy than in patients without epilepsy. SIGNIFICANCE: These results suggest a dysregulation of ADK in astrocytic brain tumors. Moreover, the upregulation of ADK observed in peritumoral infiltrated tissue of glioma patients with epilepsy supports the role of this enzyme in tumor associated epilepsy. PMID- 22092113 TI - Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan. AB - CONTEXT: Alternative strategies are being employed to develop liquid oral sustained release formulation. These included ion exchange resin, sustained release suspensions and in situ gelling systems. The later mainly utilizes alginate solutions that form gels upon contact with calcium which may be administered separately or included in the alginate solution as citrate complex. This complex liberates calcium in the stomach with subsequent gellation. The formed gel can break after gastric emptying leading to dose dumping. OBJECTIVE: Development of modified in situ gelling system which sustain dextromethorphan release in the stomach and intestine. METHODS: Solutions containing alginate with calcium chloride and sodium citrate were initially prepared to select the formulation sustaining the release in the stomach. The best formulation was combined with chitosan. All formulations were characterized with respect to flow, gelling capacity, gelling strength and drug release. RESULTS: Increasing the concentration of alginate increased the gelling capacity and strength and reduced the rate of drug release in gastric conditions with 2% w/v alginate being the best formulation. However, these formulations failed to sustain the release in the intestinal conditions. Incorporation of chitosan with alginate increased the gelling capacity and strength and reduced the rate of drug release compared to alginate only system. The effect was optimum in formulation containing 1.5% w/v chitosan. The sustained release pattern was maintained both in the gastric and intestinal conditions and was comparable to that obtained from the marketed product. CONCLUSION: Alginate-chitosan based in situ gelling system is promising for developing liquid oral sustained release. PMID- 22092112 TI - Growth velocity during infancy and onset of asthma in school-aged children. AB - BACKGROUND: Growth velocities during infancy might affect the risk of asthma in childhood. This study examines the association between peak height and weight velocities during the first 2 years of life and onset of asthma and wheeze up to 10 years of age. METHODS: Data from 9086 children who participated in the GINIplus and LISAplus birth cohorts were analyzed. Information on asthma was requested annually from 1 to 10 years and information on wheeze at 1, 2, 4, 6, and 10 years. Peak height and weight velocities were calculated using height and weight measurements obtained between birth and 2 years of age. Cox proportional hazards models and generalized linear mixed models were calculated after adjustment for potential confounding factors including birth weight and body mass index at 10 years of age. RESULTS: Per interquartile range increase in peak weight velocity (PWV), the risk of asthma increased significantly (adjHR: 1.22; CI: 1.02-1.47). The relationship between peak height velocity (PHV) and onset of asthma was nonsignificant (adjHR: 1.08; CI: 0.88-1.31). Wheeze was not significantly associated with PHV or with PWV (adjOR: 1.07; CI: 0.64-1.77 and adjOR: 1.11; CI: 0.68-1.79, respectively). CONCLUSIONS: Weight gain during infancy is positively associated with physician-diagnosed asthma in school-aged children. PMID- 22092114 TI - Growth references for Brazilian children and adolescents: healthy growth in Cariri study. AB - AIM: To construct reference values for height, body mass and BMI of children and adolescents from the Cariri region, Brazil; to compare the growth of Cariri children with those from CDC (Centers for Disease Control and Prevention) and with references from other Brazilian regions; to verify the associations between socioeconomic status and height, body mass and BMI in children and youth from both sexes. SUBJECTS AND METHODS: The sample comprised 3311 girls and 3280 boys aged 7-17 years, participating in the study 'Healthy Growth in Cariri'. Socioeconomic status was defined according to school attendance: private and public. Centile curves for height, body mass and BMI were constructed using the LMS method. RESULTS: Significant differences between children and adolescents from Cariri and those from other Brazilian regions and the CDC references were found for height and body mass. In girls from private schools, average differences in height compared to the CDC references ranged from 0.79-5.9 cm and in boys from 2.9-8.6 cm. CONCLUSION: Children from Cariri show a growth pattern in height, body mass and BMI that closely resembles the patterns observed in developed countries, but the absolute values in height and body mass are markedly lower than CDC references and growth references for other regions in Brazil. PMID- 22092115 TI - Location of cancer surgery for older veterans with cancer. AB - OBJECTIVE: Many veterans undergo cancer surgery outside of the Veterans Health Administration (VHA). We assessed to what extent these patients obtained care in the VHA before surgery. DATA SOURCES: VHA-Medicare data, VHA administrative data, and Veterans Affairs Central Cancer Registry data. STUDY DESIGN: We identified patients aged >=65 years in the VHA-Medicare cohort who underwent lung or colon cancer resection outside the VHA and assessed VHA visits in the year before surgery. PRINCIPAL FINDINGS: Over 60% of patients in the VHA-Medicare cohort who received lung or colon cancer surgeries outside the VHA did not receive any care in VHA before surgery. CONCLUSIONS: Veterans' receipt of major cancer surgery outside the VHA probably reflects usual private sector care among veterans who are infrequent VHA users. PMID- 22092116 TI - Genetic and environmental influences on personality profile stability: unraveling the normativeness problem. AB - The present study is the first to disentangle the genetic and environmental influences on personality profile stability. Spanning a period of 10 years, we analyzed the etiology of 3 aspects of profile stability (overall profile stability, distinctive profile stability, and profile normativeness) using self- and peer reports from 539 identical and 280 fraternal twins reared together. This 3-wave multirater twin design allowed us to estimate the genetic and environmental effects on latent true scores of the 3 aspects of profile stability while controlling for method effects and random error. Consistent biometric results were only found for profile normativeness, whereas overall and distinctive profile stability scores turned out to be biased. Over time, we found personality profile normativeness to be relatively stable. This stability was due to both stable genetic and nonshared environmental effects, whereas innovative variance was completely explained by nonshared environmental effects. Our findings emphasize the importance of distinguishing between the different aspects of profile stability, since overall and distinctive stability scores are likely biased due to the normativeness problem. Yet indicating a person's similarity to the average person, the normativeness of a personality profile itself has a psychological meaning beyond socially desirable responding. PMID- 22092121 TI - Ultrasonography in the management of the airway. AB - In this study, it is described how to use ultrasonography (US) for real-time imaging of the airway from the mouth, over pharynx, larynx, and trachea to the peripheral alveoli, and how to use this in airway management. US has several advantages for imaging of the airway - it is safe, quick, repeatable, portable, widely available, and it must be used dynamically for maximum benefit in airway management, in direct conjunction with the airway management, i.e. immediately before, during, and after airway interventions. US can be used for direct observation of whether the tube enters the trachea or the esophagus by placing the ultrasound probe transversely on the neck at the level of the suprasternal notch during intubation, thus confirming intubation without the need for ventilation or circulation. US can be applied before anesthesia induction and diagnose several conditions that affect airway management, but it remains to be determined in which kind of patients the predictive value of such an examination is high enough to recommend this as a routine approach to airway management planning. US can identify the croicothyroid membrane prior to management of a difficult airway, can confirm ventilation by observing lung sliding bilaterally and should be the first diagnostic approach when a pneumothorax is suspected intraoperatively or during initial trauma-evaluation. US can improve percutaneous dilatational tracheostomy by identifying the correct tracheal-ring interspace, avoiding blood vessels and determining the depth from the skin to the tracheal wall. PMID- 22092122 TI - Monitoring patients at risk of massive transfusion with Thrombelastography or Thromboelastometry: a systematic review. AB - BACKGROUND: Thrombelastography (TEG) and Thrombelastometry (ROTEM) are viscoelastic whole-blood assays evaluating the haemostatic capacity of blood. These devices are used in algorithms to guide transfusion of haemostatic blood components. METHODS: The methods used for this study were systematic reviews with meta-analyses and trial sequential analyses of randomised clinical trials (RCTs) of TEG/ROTEM-based algorithm compared with standard treatment in patients with bleeding. Primary outcome was all-cause mortality. We searched the literature in seven databases (up to 31 October 2010), reference lists, registers of ongoing trials, and contacted authors and experts. We extracted data from included studies related to study methods, interventions, outcomes, bias risk and adverse events using Cochrane methodology. All trials irrespective of blinding or language status were included. RESULTS: Nine trials involving 776 participants were included. Eight trials involved cardiac surgery with an average blood loss of 390-960 ml, and one trial investigated liver transplantations. One trial was classified as low-risk-of-bias trial. We found two ongoing trials. No impact was identified on mortality, amount of blood transfused, incidence of surgical reinterventions, time to extubation, or length of stay in hospital and intensive care unit. We identified a significant reduction in blood loss favouring the use of TEG/ROTEM {85 ml [95% confidence interval (CI) 29.4-140.7]} and in the proportion of patients receiving freshly frozen plasma and platelets [relative risk 0.39 (95%CI 0.27-0.57)]. CONCLUSION: There is currently weak evidence to support the use of TEG/ROTEM as a tool to guide transfusion in patients with severe bleeding. Further studies need to address other clinical settings and with larger blood losses. PMID- 22092123 TI - Temporal comparison of ultrasound vs. auscultation and capnography in verification of endotracheal tube placement. AB - BACKGROUND: This study compared the time consumption of bilateral lung ultrasound with auscultation and capnography for verifying endotracheal intubation. METHODS: A prospective, paired, and investigator-blinded study carried out in the operating theatre. Twenty-five adult patients requiring endotracheal intubation were included. During intubation, transtracheal ultrasound was performed to visualize passage of the endotracheal tube. During bag ventilation, bilateral lung ultrasound was performed for the detection of lung sliding as a sign of ventilation simultaneous with capnography and auscultation of the epigastrium and chest. Primary outcome measure was time difference to confirmed endotracheal intubation between ultrasound and auscultation alone. Secondary outcome measure was time difference between ultrasound and auscultation combined with capnography. RESULTS: Both methods verified endotracheal tube placement in all patients. In 68% of patients, endotracheal tube placement was visualized by real time transtracheal ultrasound. Comparing ultrasound with the combination of auscultation and capnography, there was a significant difference between the two methods. Median time for ultrasound was 40 s [interquartile range (IQR) 35-48 s] vs. 48 s (IQR 45-53 s), P < 0.0001. Mean difference was -7.1 s in favour of ultrasound [95% confidence interval (CI) -9.4--4.8 s]. No significant difference was found between ultrasound compared with auscultation alone. Median time for auscultation alone was 42 s (IQR 37-47 s), P = 0.6, with a mean difference of 0.88 s in favour of ultrasound (95% CI -4.2-2.5 s). CONCLUSIONS: Verification of endotracheal tube placement with ultrasound is as fast as auscultation alone and faster than the standard method of auscultation and capnography. PMID- 22092124 TI - Dexamethasone has additive effect when combined with ondansetron and droperidol for treatment of established PONV. AB - BACKGROUND: Prophylactic dexamethasone, ondansetron and droperidol have a documented effect on post-operative nausea and vomiting (PONV). Still, there is a lack of studies investigating the effect of adding dexamethasone to ondansetron and droperidol in order to treat established PONV. METHODS: In this double-blind randomised, controlled trial, we compared triple prophylaxis for PONV consisting of dexamethasone 8 mg intravenous (IV), ondansetron 4 mg IV and droperidol 0.625 mg IV (n = 157) with placebo (n = 156) given before gynaecological day-case surgery. Subsequently, in those having PONV despite triple prophylaxis or placebo, a dose of ondansetron and droperidol plus dexamethasone was compared with the combination of ondansetron and droperidol. RESULTS: Triple prophylaxis reduced acute PONV (0-6 h) (P = 0.0003) and post-discharge PONV (6-24 h) (P = 0.001) when compared with placebo. Among those suffering from PONV despite placebo or active prophylaxis (n = 80), adding dexamethasone to ondansetron and droperidol reduced acute PONV (0-6 h) (P = 0.025) as well as post-discharge nausea (6-24 h) (P = 0.04) compared with duo treatment comprising ondansetron and droperidol. In those reporting PONV despite prophylaxis (n = 12), the treatment comprising ondansetron and droperidol, with or without dexamethasone, gave a 91.7% reduction in acute PONV and an 83.6% reduction in post-discharge PONV. CONCLUSION: Treatment of established PONV comprising ondansetron and droperidol, with or without dexamethasone, reduced PONV in both treatment groups. In those reporting PONV without active prophylaxis, the addition of dexamethasone resulted in a significant amplification of the PONV-reducing [corrected] effects of ondansetron and droperidol. PMID- 22092125 TI - A pilot study of the implementation of WHO surgical checklist in Finland: improvements in activities and communication. AB - BACKGROUND: World Health Organisation (WHO) has introduced a surgical safety checklist that has reduced post-operative morbidity and mortality. Prior to national checklist implementation, we assessed its possible impact on the operating room (OR) process, safety-related issues and communication among surgical staff in a high-income country. METHODS: In four university and teaching hospitals, a structured questionnaire was delivered to OR personnel involved in consecutive operations over 4-6 weeks before and after the checklist implementation. The questionnaire resembled the WHO checklist and comprised multiple-choice questions relating to performance of safety checks and communication. Anaesthesiologists (A), surgeons (S) and circulating nurses (CN) answered the questions independently. The WHO checklist was modified for national needs. RESULTS: Questionnaires were returned from 1748 operations, 901 before and 847 after the checklist. Patient's identity was more often confirmed (A: 62.7% vs. 84.0%, S: 71.6% vs. 85.5%, CN: 81.6% vs. 94.2%, P < 0.001) and knowledge of names and roles among team members (A: 65.7% vs. 81.8%, S: 71.1% vs. 83.6%, CN: 87.7% vs. 93.2%, P < 0.01) improved with the checklist. Anaesthesiologists and surgeons discussed critical events pre-operatively (A: 22.0% vs. 42.6%, S: 34.7% vs. 46.2%, P < 0.001) more frequently after the checklist. In addition, fewer communication failures (43 vs. 17, P < 0.05) were reported with checklist. CONCLUSIONS: The checklist increased OR teams' awareness of patient-related issues, the procedure and expected risks. It also enhanced team communication and prevented communication failures. Our findings support use of the WHO checklist in various surgical fields. PMID- 22092126 TI - Dose-dependent attenuation by fentanyl on cough during emergence from general anesthesia. AB - BACKGROUND: Although fentanyl suppresses tracheal tube-induced cough during anesthetic recovery, it has not been proven if its antitussive effect is dose dependent and complication free. The purpose of this study is to evaluate the relationship between fentanyl doses and cough suppression during emergence from sevoflurane anesthesia. METHODS: Sixty patients undergoing thyroidectomy were randomly allocated to one of four groups (F0, F1, F1.5, and F2) according to the fentanyl dose (0 mcg/kg, 1 mcg/kg, 1.5 mcg/kg, or 2 mcg/kg). Fentanyl was administered immediately after sevoflurane discontinuation. Coughing was assessed throughout the periextubation period. The relationship between fentanyl dose and incidence of cough was analyzed using Cochran-Armitage trend test. Incidence of more than 30% elevation of mean arterial pressure (MAP) and heart rate (HR), awakening time, extubation time, and respiratory rate after extubation were recorded and compared using Mantel-Haenszel chi-square test and one-way analysis of variance. RESULTS: Fentanyl suppressed emergence cough in a dose-related manner (P = 0.002), and the ED(50) and ED(90) were 1.1 mcg/kg and 2.1 mcg/kg, respectively. The higher dose of fentanyl further reduced the number of patient with MAP and HR elevation (P = 0.003 and 0.005, respectively). Awakening time (8.4 +/- 1.9 min) in F2 was comparable with that in F1 and F1.5. Respiratory rate (9 +/- 2 bpm) and extubation time (11.9 +/- 1.8 min) in F2 were only different from those in F0 (13 +/- 3 bpm and 10.4 +/- 1.1 min, respectively). CONCLUSIONS: Fentanyl suppressed cough in a dose-related manner during recovery from general sevoflurane anesthesia, and 2 mcg/kg may be considered as a proper dose. PMID- 22092127 TI - Photoplethysmographic and pulse pressure variations during abdominal surgery. AB - BACKGROUND: Respiratory variations in pulse pressure (DeltaPP) predict fluid responsiveness during mechanical ventilation. Variations in pulse oximetry plethysmography amplitude (DeltaPOP) are proposed as a non-invasive alternative. Large variations in DeltaPOP and poor agreement between DeltaPP and DeltaPOP are found in intensive care unit patients. General anaesthesia is suggested to reduce variability of DeltaPOP and improve agreement between the variables. We evaluated the variability of the agreement between and the diagnostic values of DeltaPP and DeltaPOP during ongoing open abdominal surgery. The variability of diagnostic methods in specific clinical conditions is important, as this reflects the stability over time during which clinical decisions are made. METHODS: Observational study during open abdominal surgery in general anaesthesia. DeltaPP and DeltaPOP were calculated semi-automatically from recording periods of approximately 5 min both before and after fluid challenges. Fluid responsiveness was evaluated by changes in stroke volume (oesophageal Doppler) after 250 ml colloid. RESULTS: Thirty-four fluid challenges were performed in 25 patients. Variance both within registration periods and between patients were significantly larger for DeltaPOP than for DeltaPP (54.1% vs. 22.1% and 69.6% vs. 22.6%, respectively, both P < 0.001). Limits of agreement with a regression-based correction were +/- 13.9%. Areas under receiver operating characteristics curves for fluid responsiveness were 0.67 for DeltaPP and 0.72 for DeltaPOP. CONCLUSIONS: Analysis of raw signals during open abdominal surgery documents that the variance of DeltaPOP is larger than of DeltaPP, with wide limits of agreement between DeltaPP and DeltaPOP. The diagnostic values of DeltaPP and DeltaPOP are relatively poor. PMID- 22092128 TI - Validation and usefulness of the Danish version of the Pain Medication Questionnaire in opioid-treated chronic pain patients. AB - BACKGROUND: Addiction is a feared complication of long-term opioid therapy for chronic pain patients. A screening tool to assess the potential risk of addiction may be helpful. METHODS: The Pain Medication Questionnaire (PMQ) was translated into Danish by a 'forward' and 'backward' translation procedure. Patients with chronic non-cancer pain and cancer pain treated at a tertiary pain center were screened for addiction using Portenoy's criteria and invited to answer the Danish version of the PMQ. RESULTS: Two hundred nine patients participated in the study. PMQ was able to discriminate between addicted and non-addicted patients. Patients with high PMQ scores indicating a risk of addiction drank more alcohol, smoked more tobacco, used higher doses of morphine, had a higher anxiety and depression score, and had poorer mental health. Using a cut-off score of 22, the PMQ had a sensitivity of 82%, but the specificity at this cut-point was 56%, indicating a risk of false positive cases. Convergent and discriminant validity were confirmed by correlation with opioid doses, alcohol and tobacco use, anxiety and depression scores, and inverse correlation with mental health and social role. Test-retest showed a very strong correlation. Cronbach's alpha for internal consistency was 0.61. Ten components were found to have eigenvalues above 1.0, confirming the multidimensional structure of the questionnaire. CONCLUSIONS: The PMQ may assist physicians in addiction risk assessment and stratification when treating chronic pain patients with opioids. PMQ is not a diagnostic tool and should only be used as an indicator for possible addiction problems. PMID- 22092129 TI - Noninvasive tissue oxygen saturation determined by near-infrared spectroscopy following peripheral nerve block. AB - BACKGROUND: Noninvasive physiologic measurement of cutaneous tissue oxygenation using near-infrared spectroscopy (NIRS) has become increasingly common in cardiovascular and plastic surgery. The aim of this study was to determine whether clinically available NIRS-based monitors could detect changes in tissue oxygen saturation (rSO(2)) following a variety of peripheral nerve blocks. We hypothesize that peripheral nerve blocks will produce detectable changes in cutaneous tissue oxygenation levels that can be measured by noninvasive NIRS based oximetry. METHODS: Forty adult patients scheduled for pre-operative peripheral nerve block placement were enrolled. Prior to block placement, NIRS sensors were placed on the operative and nonoperative (control) limb. Baseline tissue oxygen saturation values were obtained prior to dosing of the nerve block, and measurements were recorded every 5 min thereafter. RESULTS: Initial rSO(2) values were higher in the operative vs. control limbs prior to nerve block placement. Tissue oxygen saturation increased in the blocked, but not control, limbs with time. Subgroup analysis suggested statistically significant differences in rSO(2) values in blocked vs. control limbs for cervical paravertebral, infraclavicular, and femoral nerve blocks. CONCLUSIONS: Our results demonstrated sustained increases in tissue rSO(2) values following peripheral nerve block placement, in addition to higher initial rSO(2) values in operative limbs prior to block placement. Further investigations are necessary to define the expected baseline rSO(2) values in operative and control limbs. Future efforts utilizing NIRS-based detection of tissue ischemia should consider the small but significant changes in rSO(2) resulting from a successful nerve block. PMID- 22092130 TI - Sonoanatomy of the vasculature at the supraclavicular and interscalene regions relevant for brachial plexus block. AB - BACKGROUND: Our aim in this observational study was to utilize ultrasound, as well as anatomic dissection, to document the frequency with which branches of the subclavian vessels are found in close association with the brachial plexus at the locations of supraclavicular and interscalene brachial plexus block. METHODS: Ultrasound was utilized to document the presence of branches of the subclavian vein and artery, adjacent to the brachial plexus in the supraclavicular and in the interscalene region in 50 patients undergoing shoulder surgery. The position, depth, and dimensions of the vessels were described, and the origin determined when possible. In addition, the posterior triangle of the neck on both sides of three non-preserved cadavers was dissected to evaluate the vascular anatomy and correlate the ultrasound findings. RESULTS: Ultrasound scanning revealed an arterial branch adjacent to, or passing directly through, the brachial plexus in the supraclavicular region in 43/50 (86%) patients. Within the interscalene region, an artery was identified coursing in a lateral direction in 45/50 (90%) of cases, while a corresponding small vein, coursing medial to lateral in this area, was noted in 23/50 (46%) of cases. CONCLUSIONS: Small branch vessels from the subclavian artery and vein were frequently evident, on ultrasound imaging, in close association with the nerve elements of the brachial plexus in the supraclavicular and interscalene regions. Appreciation of the presence of these vessels and their likely origin and course will aid the anesthesiologist in planning a safe nerve block. PMID- 22092131 TI - Hospital and long-term outcomes of ICU-treated severe community- and hospital acquired, and ventilator-associated pneumonia patients. AB - BACKGROUND: Our purpose was to analyse the association of pneumonia types with hospital and long-term outcomes of intensive care unit (ICU)-treated pneumonia patients. METHODS: The occurrence of pneumonia was retrospectively evaluated among prospectively registered patients admitted into a mixed university-level ICU during a 14-month period. Their age, severity of underlying disease, malignancy, immunosuppressive therapy and organ dysfunctions were recorded, as well as the length of hospital stay and short- and long-term mortalities. RESULTS: There were 117 severe community-acquired pneumonia (SCAP), 66 hospital acquired pneumonia (HAP) and 25 ventilator-associated pneumonia (VAP) cases among the 817 patients admitted. ICU and hospital mortality did not differ between pneumonia groups. VAP and HAP patients had more malignant underlying diseases than SCAP patients (P < 0.001). HAP patients were older than SCAP and VAP patients (P = 0.023). The admission Acute Physiology and Chronic Health Evaluation II scores did not differ between the groups (P > 0.90). The patients with VAP had higher Sequential Organ Failure Assessment maximum scores compared with patients with SCAP and HAP (P < 0.001). In an adjusted multivariate logistic regression model, there were no significant differences in odds ratios for hospital mortality between the three pneumonia types. Mortality among the hospital survivors during the 12-month follow-up period was 18% (16/89) in the SCAP group, 35% (18/51) in the HAP group and 41% (7/17) in the VAP group (P = 0.023). CONCLUSION: The type of pneumonia (i.e. SCAP, HAP or VAP) had no significant association with hospital mortality, whereas the SCAP patients had the lowest 1-year mortality. PMID- 22092132 TI - Neurally adjusted ventilatory assist vs. pressure support ventilation in critically ill patients: an observational study. AB - BACKGROUND: During neurally adjusted ventilatory assist (NAVA), the inspiratory support is controlled by the patients' respiratory drive influenced by an operator-controlled gain factor (NAVA level). The purpose of our observational study was to transfer patients from conventional pressure support ventilation (PSV) to NAVA safely. We compared two approaches to set the NAVA level and evaluated the effect of NAVA. METHODS: We studied mechanically ventilated patients capable of spontaneous breathing. For the change of the ventilator mode, we used a NAVA level calculated to generate a peak inspiratory pressure equal to PSV. We compared this NAVA level with a NAVA level determined by a NAVA level titration. Ventilatory and haemodynamic data were recorded during an observational period of 6 h. RESULTS: All 20 patients included in the study could be transferred from PSV to NAVA and completed the observation interval. Setting the NAVA level according to prior PSV settings proved to be a feasible approach, but in 75% of our patients, we modified the NAVA level according to the titration results. Gas exchange and ventilatory mechanics during the observation interval remained stable. CONCLUSIONS: The ventilator mode NAVA seems to be well tolerated in a heterogeneous group of critically ill patients. Pre-setting of the NAVA level during PSV can result in an overestimation of the required ventilator support. An additional titration of the NAVA level ads valuable information although difficult to interpret in some cases. PMID- 22092133 TI - Dexmedetomidine attenuates remote lung injury induced by renal ischemia reperfusion in mice. AB - BACKGROUND: Renal ischemia-reperfusion (I/R) may cause acute lung injury (ALI). The mortality of combined acute kidney injury and ALI is extremely high. Dexmedetomidine, an alpha(2) adrenergic agonist, exerts potent anti-inflammatory and organoprotective effects in addition to its sedative and analgesic properties. We sought to elucidate whether dexmedetomidine can attenuate lung injury following renal I/R in a murine model of renal I/R. METHODS: Adult C57BL/6J male mice were randomized to five groups: sham-operated control (Sham); renal I/R (I/R); intraperitoneal injection of dexmedetomidine 25 MUg/kg before ischemia (pre-dex) and after perfusion (post-dex); combination of alpha(2) adrenergic antagonist atipamezole 250 MUg/kg prior to dexmedetomidine pre treatment (atip-dex). Kidney I/R was induced by bilateral renal pedicle clamping for 45 min and followed by 6 h reperfusion. The pulmonary tissues were harvested for histopathological evaluation, wet/dry ratio measurement, biochemical analysis of myeloperoxidase (MPO), Polymerase chain reaction (PCR) determination of Inter cellular adhesion molecule (ICAM-1) and Tumor necrosis factor - alpha (TNF-alpha) mRNA. RESULTS: Renal IR induced significant pulmonary injuries, increased wet/dry ratio together with the enhanced of MPO activities and increased ICAM-1 and TNF alpha mRNA level. Both pre- and post-treatment with dexmedetomidine markedly reduced lung edema and inflammatory response and lowered MPO activity and ICAM-1 and TNF-alpha mRNA expression. The protective effects of dexmedetomidine in the lung were partially reversed by atipamezole, but there were no effect on ICAM-1 and TNF-alpha mRNA expression level. CONCLUSIONS: Dexmedetomidine is capable of attenuating remote lung injury induced by renal IR via both alpha(2) adrenoceptors dependent and independent mechanisms. PMID- 22092134 TI - Anaphylaxis to ethylene oxide - a rare and overlooked phenomenon? AB - Spina bifida patients have been reported to be at increased risk of anaphylactic reactions during general anaesthesia. Following a reaction, latex is often incriminated as spina bifida patients are known to have an increased incidence of latex allergy. Ethylene oxide (EO) has recently been suggested to be an alternative cause, but in many cases reported in the literature, it seems that EO has not been considered as a cause. EO is a highly reactive gas widely used to sterilise heat-sensitive medical devices, and traces of EO can be found in many of the same products as latex. We present the case of a spina bifida patient with a known latex allergy, where EO was found to be the cause of an anaphylactic reaction during general anaesthesia. In addition, we describe measures taken during preparation of a subsequent general anaesthesia to minimise exposure to EO. Spina bifida patients seem to be at increased risk of sensitisation against EO due to repeated exposure, but only limited literature is available. To ensure that EO is considered as a cause in these cases, we recommend that testing for latex and EO go hand in hand following an anaphylactic reaction in this high-risk population. PMID- 22092136 TI - A new and simple method for the correct localization of the intra-aortic balloon: the celiac artery Doppler ultrasound. PMID- 22092135 TI - Comparing axillary with infraclavicular perineural catheters for post-operative analgesia. PMID- 22092137 TI - Design and use of nerve stimulator needle-a novel technique. PMID- 22092139 TI - Ecology and metagenomics of soil microorganisms. PMID- 22092140 TI - Synthesis and characterization of a metal-to-polyoxometalate charge transfer molecular chromophore. AB - [P(4)W(35)O(124){Re(CO)(3)}(2)](16-) (1), a Wells-Dawson [alpha(2) P(2)W(17)O(61)](10-) polyoxometalate (POM)-supported [Re(CO)(3)](+) complex containing covalent W(VI)-O-Re(I) bonds has been synthesized and characterized by several methods, including X-ray crystallography. This complex shows a high visible absorptivity (epsilon(470 nm) = 4000 M(-1) cm(-1) in water) due to the formation of a Re(I)-to-POM charge transfer (MPCT) band. The complex was investigated by computational modeling and transient absorption measurements in the visible and mid-IR regions. Optical excitation of the MPCT transition results in instantaneous (<50 fs) electron transfer from the Re(I) center to the POM ligand. PMID- 22092141 TI - Synthesis of branched dithiotrisaccharides via ring-opening reaction of sugar thiiranes. AB - Satisfactory procedures are described for the synthesis of 5,6- and 3,4-thiirane derivatives from the respective hexofuranose or hexopyranose epoxide precursors. The controlled ring-opening reaction of thiiranes by 1-thioaldoses was successfully accomplished to afford, regio- and stereoselectively, beta-S-(1->4) 3,4-dithiodisaccharides. For instance, the regioselective attack of per-O-acetyl 1-thioglucose (16) to C-4 of 2-propyl 2,6-di-O-acetyl-3,4-epithio-alpha-D galactopyranoside (14) gave the derivative of Glcp-beta-S-(1->4)-3,4-dithioGlcp-O iPr (17). This thiodisaccharide was accompanied by the (1->3)-disulfide 18, formed between 16 and 17, and the symmetric (3->3)-disulfide 19, which resulted from the oxidative dimerization of 17. However, the S-acetyl derivative of 17 could be obtained in good yield (62%) by LiAlH(4) reduction of the crude mixture 17-19, followed by acetylation. The same sequence of reactions starting from 14 and the 1-thiolate of Galp afforded the per-O,S-acetyl derivative of Galp-beta-S (1->4)-3,4-dithio-alpha-D-Glcp-O-iPr (23), which was selectively S-deacetylated to give 25. The dithiosaccharides 17 and 25 are 3,4-di-S-analogues of derivatives of the natural disaccharides cellobiose and lactose, respectively. The ring opening reaction of 5,6-epithiohexofuranoses of D-galacto (8) or L-altro (11) configuration with 1-thioaldoses was also regio- and stereoselective to give the respective beta-S-(1->6)-linked 5,6-dithiodisaccharides 26 or 29 in excellent yields. Glycosylation of the free thiol group of 17, 25, or 26, using trichloroacetimidates as glycosyl donors, led to the corresponding branched dithiotrisaccharides. Some of them are sulfur analogues of derivatives of branched trisaccharides found in natural polysaccharides. PMID- 22092142 TI - Belongingness as a core personality trait: how social exclusion influences social functioning and personality expression. AB - People have a fundamental need for positive and lasting relationships. This need to belong is rooted in evolutionary history and gave rise to the development of traits that enable individuals to gain acceptance and to avoid rejection. Because belongingness is a core component of human functioning, social exclusion should influence many cognitive, emotional, and behavioral outcomes and personality expression. This article summarizes recent evidence that social exclusion causes an assortment of outcomes, many of which depend on whether the excluded can gain acceptance or forestall possible distress. It highlights common overlap in physical and social pain systems and how a physical painkiller can reduce the pain of social exclusion. Finally, it shows how social exclusion moderates the effects of traits on cognition, emotion, and behavior. To appreciate personality processes in social contexts, scientists should consider how people respond to social exclusion and how the need to belong influences personality expression. PMID- 22092144 TI - How does temporal preparation speed up response implementation in choice tasks? Evidence for an early cortical activation. AB - We investigated the influence of temporal preparation on information processing. Single-pulse transcranial magnetic stimulation (TMS) of the primary motor cortex was delivered during a between-hand choice task. The time interval between the warning and the imperative stimulus varied across blocks of trials was either optimal (500 ms) or nonoptimal (2500 ms) for participants' performance. Silent period duration was shorter prior to the first evidence of response selection for the optimal condition. Amplitude of the motor evoked potential specific to the responding hand increased earlier for the optimal condition. These results revealed an early release of cortical inhibition and a faster integration of the response selection-related inputs to the corticospinal pathway when temporal preparation is better. Temporal preparation may induce cortical activation prior to response selection that speeds up the implementation of the selected response. PMID- 22092143 TI - When curiosity breeds intimacy: taking advantage of intimacy opportunities and transforming boring conversations. AB - Curious people seek knowledge and new experiences. In 3 studies, we examined whether, when, and how curiosity contributes to positive social outcomes between unacquainted strangers. Study 1 (98 college students) showed that curious people expect to generate closeness during intimate conversations but not during small talk; less curious people anticipated poor outcomes in both situations. We hypothesized that curious people underestimate their ability to bond with unacquainted strangers during mundane conversations. Studies 2 (90 college students) and 3 (106 college students) showed that curious people felt close to partners during intimate and small-talk conversations; less curious people only felt close when the situation offered relationship-building exercises. Surprise at the pleasure felt during this novel, uncertain situation partially mediated the benefits linked to curiosity. We found evidence of slight asymmetry between self and partner reactions. Results could not be attributed to physical attraction or positive affect. Collectively, results suggest that positive social interactions benefit from an open and curious mind-set. PMID- 22092145 TI - Long-term outcome after acute renal replacement therapy: a narrative review. AB - BACKGROUND: Acute kidney injury (AKI) necessitating renal replacement therapy (RRT) is associated with high short-term mortality, relatively little however is known of the long-term outcome in these patients. This narrative review describes renal recovery, long-term mortality, and quality of life in RRT patients with acute kidney injury. METHODS: A literature search using the PubMed search engine from the year 2000 to present with the MeSH terms 1) acute kidney injury, renal replacement therapy, prognosis, and 2) acute kidney injury, quality of life, prognosis, was performed, including studies addressing long-term outcome (over 60 days) in adults with AKI on RRT. RESULTS: According to inclusion criteria, twenty two studies were eligible. Outcome varied depending on AKI aetiology, setting, co morbidity and pre-morbid renal function. Five-year-survival was between 15% and 35%, with dialysis dependence in less than 10% of survivors. Renal recovery, even if incomplete occurred during the first year. Quality of life assessment amongst survivors indicated moderate physical impairment and reduced mental health scores. A majority of patients returned to employment and self-sustainability and reported acceptable to good quality of life. Over 90% of patients indicated that they would undergo the same treatment again. DISCUSSION AND CONCLUSIONS: Early initiation of treatment and fine-tuning of the RRT technique may improve outcome. Consensus regarding AKI definitions, renal function measurement and standardised follow-up regimens are required. Further long-term studies are needed. PMID- 22092146 TI - Group 15 pnictenium cations supported by a conjugated bithiophene backbone. AB - Thiophene based polymers and oligomers have attracted considerable attention because they can be functionalized to alter the gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), which enables the design of tunable light emitting materials. One area, which has been less explored, is the incorporation of low coordinate, low oxidation state main group elements into these systems. We have currently developed a novel pi conjugated ligand containing two contiguous thiophene rings in which we have demonstrated its ability to support both pnictogen cations and their metal complexes. PMID- 22092147 TI - Unilateral and bilateral laparoscopic ovariectomy in 157 mares: a retrospective multicenter study. AB - OBJECTIVE: To evaluate surgical techniques, perioperative complications and outcome of laparoscopic surgery for unilateral and bilateral ovariectomy in mares. STUDY DESIGN: Retrospective multicenter case series. ANIMALS: Mares (n = 157). METHODS: Indications for surgery were neutering, fertility problems, elimination of hormone-related abnormal behavior, ovarian tumors as well as nonregressive ovarian hematomas or cysts. Ovariectomy (n = 206) were performed by a standard laparoscopic procedure in 157 standing sedated mares. Dissection and hemostasis were achieved by using either (1) a linear stapling device, (2) bipolar electrosurgical instruments, with or without a modified Roeder knot, (3) a vessel-sealing system, or (4) a diode-laser with ligation. For some larger ovarian masses (>20 cm diameter), a 2-step surgical procedure was used with standing flank laparoscopic ovariectomy followed by ovarian retrieval through a median celiotomy. Surgical techniques, outcome, and perioperative complications of each method were recorded and analyzed. RESULTS: Laparoscopic dissection of the ovary was accomplished in all mares. Because of the size of the ovarian tumor (n = 7) or in 1 mare with behavioral problems (n = 1), the dissected ovary was removed through a median celiotomy under general anesthesia. Seventeen mares (10.8%) developed postoperative complications (eg, incisional drainage, incisional infection, seroma formation, dehiscence, transient fever and mild abdominal discomfort). All mares with flank incisional problems had ovarian size >12 cm and in 15 (88%) of these mares electrosurgical instruments were used for mesovarial dissection. CONCLUSIONS: Laparoscopic ovariectomy in standing sedated mares provides good surgical access and is associated with low morbidity. PMID- 22092148 TI - Application of sulphur isotopes for stratigraphic correlation. AB - The sulphur isotopic composition of dissolved sulphate in seawater has varied considerably through time. Certain time intervals are characterised by distinct variations and a relatively high rate of change. These relatively rapid fluctuations allow for correlation of sediment sections using sulphur isotopes. Sulphur isotope reconstructions based on the analysis of carbonate associated sulphate or marine barite result in sulphur isotope records with an age resolution of 1-5 million years (Ma), and for some age intervals the resolution is<0.25 Ma. At these specific time intervals, where higher resolution records exist and excursions in the record are identified, the trends could be used for stratigraphic correlations. Such records are particularly useful in sections from deep marine sites that lack biostratigraphic controls or where biozones do not provide sufficient resolution. PMID- 22092149 TI - Electrochemistry at nanoscale electrodes: individual single-walled carbon nanotubes (SWNTs) and SWNT-templated metal nanowires. AB - Individual nanowires (NWs) and native single-walled carbon nanotubes (SWNTs) can be readily used as well-defined nanoscale electrodes (NSEs) for voltammetric analysis. Here, the simple photolithography-free fabrication of submillimeter long Au, Pt, and Pd NWs, with sub-100 nm heights, by templated electrodeposition onto ultralong flow-aligned SWNTs is demonstrated. Both individual Au NWs and SWNTs are employed as NSEs for electron-transfer (ET) kinetic quantification, using cyclic voltammetry (CV), in conjunction with a microcapillary-based electrochemical method. A small capillary with internal diameter in the range 30 70 MUm, filled with solution containing a redox-active mediator (FcTMA(+) ((trimethylammonium)methylferrocene), Fe(CN)(6)(4-), or hydrazine) is positioned above the NSE, so that the solution meniscus completes an electrochemical cell. A 3D finite-element model, faithfully reproducing the experimental geometry, is used to both analyze the experimental CVs and derive the rate of heterogeneous ET, using Butler-Volmer kinetics. For a 70 nm height Au NW, intrinsic rate constants, k(0), up to ca. 1 cm s(-1) can be resolved. Using the same experimental configuration the electrochemistry of individual SWNTs can also be accessed. For FcTMA(+/2+) electrolysis the simulated ET kinetic parameters yield very fast ET kinetics (k(0) > 2 +/- 1 cm s(-1)). Some deviation between the experimental voltammetry and the idealized model is noted, suggesting that double layer effects may influence ET at the nanoscale. PMID- 22092150 TI - Patient participation in medical and social decisions in Alzheimer's disease. AB - OBJECTIVES: To analyze the preferences of people with amnestic mild cognitive impairment (aMCI) and mild dementia in Alzheimer's disease (AD) regarding different aspects of healthcare-related decisions, to correlate these findings with different measures of decision-making capacity, and to explore the views of relatives and referring physicians. DESIGN: Cross-sectional survey. SETTING: University-based memory clinic in Munich, Germany. PARTICIPANTS: One hundred people with aMCI or mild AD, their relatives (N = 99), and their referring physicians (N = 93). MEASUREMENTS: Participation preferences and decisional capacity and assessment of these measures according to relatives and physicians. RESULTS: Patients had a preference for participation in healthcare-related decisions, especially in social ones. Overall, individuals wanted their relatives to play a secondary role in decision-making. Relatives and referring physicians performed poorly in predicting the individuals' participation preferences, and relatives wanted to attribute less decision-making power to patients than the patients did themselves. Patients refrained from participation if they had lower Mini-Mental State Examination scores or were unsure about their decisional capacity. There were deficits in decision-making capacity, which mostly related to understanding of the information presented. There was only weak correlation between the different measures (patient's, relative's, and physician's estimate, MacArthur Competence Assessment Tool for Treatment) of the patients' decisional capacity. CONCLUSION: The combination of marked participation preferences and impairments in the decisional capacity of individuals with aMCI and early AD constitute an ethical and practical challenge. A thorough implementation of structured probes of the patients' decisional capacity combined with interventions that aid patients in their decision-making capability might help to overcome some of these challenges. PMID- 22092151 TI - The effect of testosterone supplementation on depression symptoms in hypogonadal men from the Testim Registry in the US (TRiUS). AB - OBJECTIVE: To determine the effect of long-term testosterone replacement therapy (TRT) on depression symptoms in hypogonadal men. METHODS: Data were from TRiUS, a multicenter, 12-month observational registry (N = 849) of hypogonadal men prescribed 1% testosterone gel. Measures including total testosterone (TT) were assessed at baseline and months 3, 6, and 12. Depression symptoms were measured with Patient Health Questionnaire-9 (PHQ-9), a validated self-report questionnaire. A PHQ-9 score decrease of >=5 represents clinical improvement. RESULTS: PHQ-9 scores were available for 762/849 TRiUS participants at baseline. Overall, 92.4% (704/762) demonstrated some level of depressive symptoms, with 17.3% (132/762) having moderately severe (score 15-19) to severe (score 20-27) symptoms. Subcohorts with significantly (p <= 0.03) more moderately severe to severe symptoms were: <60 years old, TT levels <250 ng/dl (<8.68 nmol/l), HIV/AIDS-positive, or used antidepressants or opioids. TT levels and PHQ-9 scores improved significantly (p < 0.01) by 3 months of TRT. At 12 months PHQ-9 scores showed a clinically meaningful mean improvement of 5.62 points, patients with moderately severe to severe symptoms decreased from 17.3% to 2.1% (5/233), and subcohorts, including those defined by age (<60 years) and antidepressant use, had improved PHQ-9 scores >=5. CONCLUSION: TRT may reduce depression symptoms in hypogonadal men, including middle-aged men and those using antidepressants. PMID- 22092153 TI - The impact of 90-day prescriptions on adherence at workplace pharmacies compared to traditional mail order. AB - This study evaluated adherence to medications used to treat chronic conditions for patients with 90-day prescriptions, comparing patients with access to workplace pharmacy services versus patients using mail order services. De identified pharmacy claims data were used to compute medication possession ratio and gaps in therapy. Results were compared for patients who filled 90-day prescriptions at workplace pharmacies versus patients who filled 90-day prescriptions using mail order pharmacy services in a 1-year period. Statistical tests to assess between group differences were performed controlling for differences because of age, sex, number of select chronic conditions, number of unique medication therapeutic classes, and patient out-of-pocket cost per therapy day. Statistically significant differences were found between patients who filled their maintenance medications at the worksite compared to those who used mail order pharmacy services. Patients filling prescriptions at a workplace pharmacy were 22% less likely to have a gap in therapy of over 30 days compared to similar patients using mail order services. Workplace pharmacy utilizers also had overall adherence rates 3.68% higher than patients who utilized mail order pharmacy services. Our analysis suggests that it may not be just the quantity of medication dispensed that impacts patients' adherence to their prescription medication, but a variety of other factors including pharmacist-patient interaction. Having a pharmacist on-site and available to patients with chronic considerations could provide added value. These results can aid employers and other stakeholders to decide which prescription benefits to offer their employees and members. PMID- 22092152 TI - Behavioral versus drug treatment for overactive bladder in men: the Male Overactive Bladder Treatment in Veterans (MOTIVE) Trial. AB - OBJECTIVES: To compare the effectiveness of behavioral treatment with that of antimuscarinic therapy in men without bladder outlet obstruction who continue to have overactive bladder (OAB) symptoms with alpha-blocker therapy. DESIGN: The Male Overactive Bladder Treatment in Veterans (MOTIVE) Trial was a two-site randomized, controlled, equivalence trial with 4-week alpha-blocker run-in. SETTING: Veterans Affairs Medical Center outpatient clinics. PARTICIPANTS: Volunteer sample of 143 men aged 42 to 88 who continued to have urgency and more than eight voids per day, with or without incontinence, after run-in. INTERVENTIONS: Participants were randomized to 8 weeks of behavioral treatment (pelvic floor muscle exercises, urge suppression techniques, delayed voiding) or drug therapy (individually titrated, extended-release oxybutynin, 5-30 mg/d). MEASUREMENTS: Seven-day bladder diaries and a validated urgency scale were used to calculate changes in 24-hour voiding frequency, nocturia, urgency, and incontinence. Secondary outcomes were global patient ratings and American Urological Association Symptom Index. RESULTS: Mean voids per day decreased from 11.3 to 9.1 (-18.8%) with behavioral treatment and 11.5 to 9.5 (-16.9%) with drug therapy. Equivalence analysis indicated that posttreatment means were equivalent (P < .01). After treatment, 85% of participants rated themselves as much better or better; more than 90% were completely or somewhat satisfied, with no between group differences. The behavioral group showed greater reductions in nocturia (mean = -0.70 vs -0.32 episodes/night; P = .05). The drug group showed greater reductions in maximum urgency scores (mean = -0.44 vs -0.12; P = .02). Other between-group differences were nonsignificant. CONCLUSION: Behavioral and antimuscarinic therapy are effective when added to alpha-blocker therapy for OAB in men without outlet obstruction. Behavioral treatment is at least as effective as antimuscarinic therapy. PMID- 22092154 TI - Acute encephalopathy in children with Dravet syndrome. AB - PURPOSE: The occurrence of acute encephalopathy in children with Dravet syndrome has been reported sporadically. This study clarified the features of acute encephalopathy in children with Dravet syndrome. METHODS: Through the mailing list of the Annual Zao Conference on Pediatric Neurology, we collected 15 patients with clinically diagnosed Dravet syndrome, who had acute encephalopathy, defined as a condition with decreased consciousness with or without other neurologic symptoms, such as seizures, lasting for >24 h in association with infectious symptoms. KEY FINDINGS: There were seven boys and eight girls. A mutation of the SCN1A gene was present in nine (truncation in six and missense in three). The frequency of seizures during the 3 months before the onset of acute encephalopathy was monthly in seven children and none in three. The median age at the onset of acute encephalopathy was 44 months (range 8-184 months). All children had status epilepticus followed by coma as the initial manifestation. Two different distributions of brain lesions were observed on diffusion-weighted images during the acute phase: cerebral cortex-dominant lesions with or without deep gray matter involvement and subcortical-dominant lesions. Four children died; nine survived with severe sequelae, and two had moderate sequelae. SIGNIFICANCE: We must be aware that acute encephalopathy is an important complication in children with Dravet syndrome, and associated with fulminant clinical manifestations and a poor outcome. PMID- 22092155 TI - Surgery wait times and specialty services for insured and uninsured breast cancer patients: does hospital safety net status matter? AB - OBJECTIVE: To determine whether safety net and non-safety net hospitals influence inpatient breast cancer care in insured and uninsured women and in white and African American women. DATA SOURCES: Six years of Virginia Cancer Registry and Virginia Health Information discharge data were linked and supplemented with American Hospital Association data. STUDY DESIGN: Hierarchical generalized linear models and linear probability regression models were used to estimate the relationship between hospital safety net status, the explanatory variables, and the days from diagnosis to mastectomy and the likelihood of breast reconstruction. PRINCIPAL FINDINGS: The time between diagnosis and surgery was longer in safety net hospitals for all patients, regardless of insurance source. Medicaid insured and uninsured women were approximately 20 percent less likely to receive reconstruction than privately insured women. African American women were less likely to receive reconstruction than white women. CONCLUSIONS: Following the implementation of health reform, disparities may potentially worsen if safety net hospitals' burden of care increases without commensurate increases in reimbursement and staffing levels. This study also suggests that Medicaid expansions may not improve outcomes in inpatient breast cancer care within the safety net system. PMID- 22092156 TI - Influence of partial lateral corpectomy with and without hemilaminectomy on canine thoracolumbar stability: a biomechanical study. AB - OBJECTIVE: To analyze the biomechanical changes induced by partial lateral corpectomy (PLC) and a combination of PLC and hemilaminectomy in a T13-L3 spinal segment in nonchondrodystrophic dogs. STUDY DESIGN: In vitro biomechanical cadaveric study. SAMPLE POPULATION: T13-L3 spinal segments (n = 10) of nonchondrodystrophic dogs (weighing, 25-38 kg). METHODS: A computed tomography (CT) scan of each T13-L3 spinal segment was performed. A loading simulator for flexibility analysis was used to determine the range of motion (ROM) and neutral zone (NZ) during flexion/extension, lateral bending, and axial rotation. A servohydraulic testing machine was used to determine the changes in stiffness during compression, dorsoventral, and lateral shear. All spines were tested intact, after PLC in the left intervertebral space of L1-L2, and after a combination of PLC and hemilaminectomy. RESULTS: Statistically significant increases in ROM and NZ (P < .05) were detected during flexion/extension and lateral bending when PLC was performed. A significant increase in ROM (P < .001) was noted during axial rotation and flexion after PLC and hemilaminectomy. Stiffness decreased significantly during compression and dorsoventral shear after each procedure. Decreased stiffness during lateral shear was only significant after a combination of both procedures. CONCLUSION: PLC might lead to some spinal instability; these changes are enhanced when a hemilaminectomy is added. PMID- 22092157 TI - The electrocoagulation/advanced oxidation treatment of the groundwater used for human consumption. AB - The purpose of this work was development and application of the purification system suitable for the treatment of groundwater used for human consumption, satisfying following criteria: (a) no need for external addition of the chemicals; (b) simultaneous removal of wide range of contaminants present in the treated water; (c) low sensitivity to the changes in the composition of the treated water; (d) high quality of treated water with regards to all measured parameters. Therefore the well water from the 60 m deep water layer situated near the city of Osijek (Eastern Croatia) with elevated values of heavy metals, color, turbidity, suspended solids, ammonia and organic contaminants was processed. Due to the complex composition of the treated water, the purification system required the combination of electroreduction/electrocoagulation, using iron and aluminum electrode plates followed by the simultaneous ozonation/UV treatment. The electroreduction/electrocoagulation approach was used for the removal of heavy metals, suspended solids, color and turbidity, while the organic contaminants and ammonia were removed by the ozonation/UV treatment. All measured parameters in the purified water were significantly lower compared to the regulated values. Under the optimum treatment conditions, the removal efficiencies for color, turbidity, nickel and arsenic were 100%. The removal efficiencies of V, Cr, Mn, Fe, Cu, Zn, Pb, ammonia, fluorides, sulfates and COD were 94.5%, 96.0%, 98.3%, 99.6%, 99.7%, 97.8%, 96.7%, 96,7%, 93.4%, 51.4%, 72.2% and 93.8%, respectively, increasing with the increased initial concentrations. PMID- 22092158 TI - Demographic differences in self-report pubertal status among rural adolescents in the US. AB - BACKGROUND: While sex and racial/ethnic differences in pubertal development have been noted, most of this research has been in urban areas. AIM: The purpose of this study is to examine demographic differences in pubertal status among a school-based sample of US rural adolescents aged 11-17 (n = 6425). METHODS: Pubertal status was measured using the Pubertal Development Scale (PDS), a self report scale of secondary sexual characteristics. This study compared pubertal status means by age, sex and race/ethnicity. RESULTS: At all ages, females had a higher mean pubertal status than males. Most racial/ethnic differences were between White and Black youth. Between the ages of 11 and 13, Black youth reported more advanced development than White youth. However, contrary to research with urban samples, this pattern of development reversed in later adolescence and the reversal was more prominent among males than females. Although there were no differences in pubertal status between White and Latino males, White females had higher mean levels of development than Latino females. CONCLUSION: Demographic patterns were both consistent with and different from previous research with urban adolescents, suggesting the need for comparison of demographic patterns of pubertal development in samples that include youth from urban and rural areas. PMID- 22092160 TI - Evaluation of the hemostatic potential including thrombin generation of three different therapeutic pathogen-reduced plasmas. AB - BACKGROUND AND OBJECTIVES: Several pathogen inactivation methods currently applied to therapeutic plasma may result in products with different hemostatic properties. This study aims at evaluating and comparing the hemostatic potential of different therapeutic plasma preparations currently available in France. MATERIALS AND METHODS: We studied three types of pathogen-reduced plasma for transfusion (MB/light, Amotosalen/UVA, industrial S/D plasma). Quarantine, non pathogen-reduced plasma, was used as a control. This study compared more specifically the content in FVIII, fibrinogen (clottable and antigen assays) and ADAMTS-13 and evaluated the intrinsic hemostatic properties using a thrombin generation test [Calibrated Automated Thrombogram (CAT)] at high and low concentrations of tissue factor to assess the maximum quantity of thrombin generated or the contribution of FVIII and FIX in the amplification phase of thrombin generation, respectively. RESULTS: The median FVIII concentration was >70 IU/dl for each preparation. Endogenous thrombin potential values were significantly different among the methods of plasma preparation (P<0.001) but were all in the range of the values measured in donors' plasma. Control by the thrombomodulin-activated protein C system was preserved in all preparations (>50% inhibition of endogenous thrombin potential). Fibrinogen concentrations were all within normal range but fibrinogen levels were lower in the plasmas treated with photochemical methods. ADAMTS-13 levels were preserved. CONCLUSION: The hemostatic potential appears well preserved in all therapeutic plasmas tested but there are some differences between preparations, the clinical relevance of which remains to be elucidated. PMID- 22092159 TI - A multi-allergen standard for the calibration of immunoassays: CREATE principles applied to eight purified allergens. AB - BACKGROUND: Allergen measurements are widely used for environmental exposure assessments and for determining the potency of allergen vaccines, yet few purified allergen standards have been developed. The aim of the study was to develop a single standard containing multiple purified allergens that could be used in enzyme immunoassays and in multiplex arrays for the standardization of allergen measurements. METHODS: Eight purified allergens were formulated into a single multi-allergen, or 'universal', standard based on amino acid analysis. Dose-response curves were compared with previous individual ELISA standards and allergen measurements of house dust extracts to obtain correction factors. Measured allergen concentrations were also modeled using linear regression, and the predictive accuracy was determined. RESULTS: Parallel dose-response curves were obtained between the universal allergen standard and the individual ELISA standards, with close agreement between curves for 5/8 allergens. Quantitative differences of greater than twofold were observed for Fel d 1, Can f 1, and Der f 1, which were confirmed by the analysis of house dust extracts. Correction factors were developed that allowed ELISA data to be expressed in terms of the universal standard. Linear regression data confirmed the predictive accuracy of the universal standard. CONCLUSION: This study shows that a single standard of eight purified allergens can be used to compare allergen measurements by immunoassay. This approach will improve the continuity of environmental exposure assessments and provide improved standardization of allergy diagnostics and vaccines used for immunotherapy. PMID- 22092161 TI - The big chill: interpersonal coldness and emotion-labeling skills. AB - Interpersonally cold (relative to warm) individuals may be less skilled in inferring the emotional states of others, a factor that should contribute to their poorer social relationships. Systematic support for this hypothesis was obtained in 4 studies (total N = 434 undergraduates) involving diverse emotion- and affect-decoding tasks. Specifically, relatively cold individuals exhibited lower accuracy in decoding emotional facial expressions (Study 1), in labeling the emotions of others from audio and video clips (Study 2), in predicting the emotions of others from social scenario descriptions (Study 3), and in the normative accuracy of their word evaluations (Study 4). Altogether, the results demonstrate that cold individuals appear broadly deficient in linking emotion and affect to relevant environmental stimuli. Implications of the findings for understanding the nature and correlates of interpersonal coldness are discussed. PMID- 22092162 TI - The hubris hypothesis: you can self-enhance, but you'd better not show it. AB - We tested whether and why observers dislike individuals who convey self superiority through blatant social comparison (the hubris hypothesis). Participants read self-superiority claims ("I am better than others"; Experiments 1-7), noncomparative positive claims ("I am good"; Experiments 1-2, 4), self equality claims ("I am as good as others"; Experiments 3-4, 6), temporally comparative self-superiority claims ("I am better than I used to be"; Experiment 5), other-superiority claims ("S/he is better than others"; Experiment 6), and self-superiority claims accompanied by persistent disclaimers (Experiment 7). They judged the claim and the claimant (Experiments 1-7) and made inferences about the claimant's self-view and view of others (Experiments 4-7) as well as the claimant's probable view of them (Experiment 7). Self-superiority claims elicited unfavorable evaluations relative to all other claims. Evaluation unfavorability was accounted for by the perception that the claimant implied a negative view of others (Experiments 4-6) and particularly of the observer (Experiment 7). Supporting the hubris hypothesis, participants disliked individuals who communicated self-superiority beliefs in an explicitly comparative manner. Self-superiority beliefs may provoke undesirable interpersonal consequences when they are explicitly communicated to others but not when they are disguised as noncomparative positive self-claims or self improvement claims. PMID- 22092163 TI - Good results from advanced trauma care in rural areas. PMID- 22092164 TI - Transfusion: is merely not bad good enough? PMID- 22092165 TI - Corticosteroid therapy in intensive care unit patients with PCR-confirmed influenza A(H1N1) infection in Finland. AB - OBJECTIVE: To evaluate the incidence, treatment, and outcome of influenza A(H1N1) in Finnish intensive care units (ICUs) with special reference to corticosteroid treatment. METHODS: During the H1N1 outbreak in Finland between 11 October and 31 December 2009, we prospectively evaluated all consecutive ICU patients with high suspicion of or confirmed pandemic influenza A(H1N1) infection. We assessed severity of acute disease and daily organ dysfunction. Ventilatory support and other concomitant treatments were evaluated and recorded daily throughout the ICU stay. The primary outcome was hospital mortality. RESULTS: During the 3-month period altogether 132 ICU patients were tested polymerase chain reaction-positive for influenza A(H1N1). Of these patients, 78% needed non-invasive or invasive ventilatory support. The median (interquartile) length of ICU stay was 4 [2-12] days. Hospital mortality was 10 of 132 [8%, 95% confidence interval (CI) 3-12%]. Corticosteroids were administered to 72 (55%) patients, but rescue therapies except prone positioning were infrequently used. Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores in patients with and without corticosteroid treatment were 31 [24-36] and 6 [2-8] vs. 22 [5-30] and 3 [2-6], respectively. The crude hospital mortality was not different in patients with corticosteroid treatment compared to those without: 8 of 72 (11%, 95% CI 4 19%) vs. 2 of 60 (3%, 95% CI 0-8%) (P = 0.11). CONCLUSIONS: The majority of H1N1 patients in ICUs received ventilatory support. Corticosteroids were administered to more than half of the patients. Despite being more severely ill, patients given corticosteroids had comparable hospital outcome with patients not given corticosteroids. PMID- 22092166 TI - Volume kinetics of acetated Ringer's solution during experimental spinal anaesthesia. AB - BACKGROUND: General anaesthesia lowers the clearance of crystalloid fluid, but the volume kinetics of such fluid throughout the duration of spinal anaesthesia has not been studied. METHODS: Ten female volunteers (mean age 29 years) received an intravenous infusion of 25 ml/kg of acetated Ringer's solution with and without spinal anaesthesia. A volume kinetic model was fitted to serial measurements of the haemoglobin concentration over 240 min based on arterial, cubital vein, and femoral vein blood. The measured urine flow was compared to the model-predicted elimination. RESULTS: The arterial pressure remained stable, although the block reached to Th3-Th5 in half of the volunteers. There were no differences in fluid kinetics between the spinal anaesthesia and the control experiments. The administered volume was well confined to the kinetic system, which consisted of two communicating fluid spaces that were 2.8 l and approximately 7 l in size at baseline. The arteriovenous difference in plasma dilution remained positive for 30 min post-infusion in those having analgesia reaching to Th3-Th5, which differed significantly from low-level analgesia (Th12 L2, P < 0.03) when venous plasma was sampled from the leg. The urinary excretion averaged 1.13 l and 1.01 l for the spinal and control experiments, respectively. Volume kinetics predicted the urinary excretion at 5- to 10-min intervals with an overall bias of 52 ml. CONCLUSION: Acetated Ringer's solution showed the same kinetics during experimental spinal anaesthesia as when the fluid was infused alone. Hence, spinal anaesthesia is not associated with the reduced fluid clearance reported for general anaesthesia. PMID- 22092167 TI - Haemostatic effect of aprotinin during craniosynostotic surgery in children. AB - BACKGROUND: Aprotinin has been used in our hospital since the year 2003 to reduce bleeding during craniosynostotic surgery in children. The aim of this retrospective study was to investigate its effect, primarily on bleeding and secondarily on the need for transfusion. METHODS: Thirteen children were treated with aprotinin from 2003 to 2008, while 39 were not treated in the period 1993 2002. Information on blood loss and need for transfusion during the operations in all 52 children was collected from their medical records. RESULTS: There was a significant difference in both blood loss and need for transfusion. Estimated blood volume was used to correct for difference in the children's age and size. In the aprotinin group, blood loss was 3.9% of circulating blood volume vs. 22.0%, and the need for transfusion was 0.0% vs. 21.1%. CONCLUSION: Blood loss and need for blood transfusion were significantly reduced in the aprotinin group. No allergic or other possible aprotinin-specific complications were registered in the aprotinin group. PMID- 22092168 TI - Effect of N-acetylcysteine on cardiac injury and oxidative stress after abdominal aortic aneurysm repair: a randomized controlled trial. AB - BACKGROUND: Several studies have reported that the antioxidant properties of N acetylcysteine (NAC) can provide cardiac protection through scavenging of free radicals. The present study was aimed to assess the efficacy of NAC for cardiac protection in patients undergoing elective abdominal aortic aneurysm (AAA) repair. METHODS: Fifty adult patients undergoing (AAA) repair were randomly allocated to receive NAC infusion (n = 25) or placebo infusion (n = 25). NAC infusion in group I (NAC group) was started at a rate of 0.3 mg/kg/min intravenously during surgery then decreased to a rate of 0.2 mg/kg/min for 24 h post-operatively. Group II (placebo group) received an equivalent rate of placebo infusion. The following parameters: myocardial-specific protein troponin-I, creatine phosphokinase-MB (CPK-MB), plasma pro-inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta], were assessed at the following time points: preoperatively and at 1 h, 12 h, 24 h, 48 h, and 96 h after surgery. Furthermore, serum malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured preoperatively as a baseline, during aortic clamping, 30 min after declamping, at the end of surgery, 2 h after surgery, 12 h after surgery, and 24 h after surgery. RESULTS: NAC infusion patients had significantly lower post-operative concentrations of myocardial-specific protein [cTnI, CPK-MB] and pro-inflammatory cytokines [TNF-alpha, IL-1beta]. In addition, MDA level was less and TAC was higher in patients who received NAC infusion. CONCLUSION: NAC infusion provided cardiac protection through scavenging of oxygen free radicals. PMID- 22092170 TI - P-type nitrogen-doped ZnO nanoparticles stable under ambient conditions. AB - Zinc oxide is considered as a very promising material for optoelectronics. However, to date, the difficulty in producing stable p-type ZnO is a bottleneck, which hinders the advent of ZnO-based devices. In that context, nitrogen-doped zinc oxide receives much attention. However, numerous reviews report the controversial character of p-type conductivity in N-doped ZnO, and recent theoretical contributions explain that N-doping alone cannot lead to p-typeness in Zn-rich ZnO. We report here that the ammonolysis at low temperature of ZnO(2) yields pure wurtzite-type N-doped ZnO nanoparticles with an extraordinarily large amount of Zn vacancies (up to 20%). Electrochemical and transient spectroscopy studies demonstrate that these Zn-poor nanoparticles exhibit a p-type conductivity that is stable over more than 2 years under ambient conditions. PMID- 22092171 TI - BF3.OEt2-promoted diastereoselective diacetoxylation of alkenes by PhI(OAc)2. AB - Selective syn and anti diacetoxylations of alkenes have been achieved using a PhI(OAc)(2)/BF(3).OEt(2) system in the presence and absence of water, respectively. A broad range of substrates including electron-deficient alkenes (such as alpha,beta-unsaturated esters) could be elaborated efficiently at room temperature with this methodology, furnishing the desired products in good to excellent yields and diastereoselectivity. In particular, a multigram-scale diastereoselective diacetoxylation of methyl cinnamate (5.00 g) was also accomplished in a few hours, maintaining the same efficiency as small-scale reaction. This novel methodology provides an alternative approach for the preparation of various 1,2-diols. PMID- 22092172 TI - Stable isotope and hydrogeochemical studies of Beaver Lake and Radok Lake, MacRobertson Land, East Antarctica. AB - Beaver Lake and Radok Lake, the largest known epishelf lake and the deepest freshwater lake on the Antarctic continent, respectively, were isotopically (delta(2)H, delta(18)O) and hydrogeochemically studied. Radok Lake is an isothermal and non-stratified, i.e. homogeneous water body, while Beaver Lake is stratified with respect to temperature, salinity, and isotopic composition. The results for the latter attest to freshwater (derived from snow and glacier melt) overlying seawater. PMID- 22092173 TI - Analysis of a genome-wide association study-linked locus (CCR6) in Asian rheumatoid arthritis. AB - A genome-wide association study in Japan identified the C-C chemokine receptor type 6 gene (CCR6) as associated with rheumatoid arthritis (RA). This finding has not been validated in other Asian populations. A case-control study involving 996 subjects, comprising 440 controls and 556 RA patients, was done to determine their anticyclic citrullinated peptide (anti-CCP) antibody status and CCR6 polymorphism (rs3093024) genotype. Three hundred eighty-seven patients were anti CCP positive and 153 anti-CCP negative. Logistic regression showed that allele A was likely to increase the risk of developing RA among females via a recessive model (odds ratio [OR]=1.55, 95% confidence interval [CI]=1.01, 2.39), whereas the risk effect appeared to be reduced among males via an additive model (OR=0.60, 95% CI=0.42, 0.85). Considering only subjects who are anti-CCP positive, allele A increased RA risk among females via a recessive model (OR=1.68, 95% CI=1.07, 2.64) but decreased the risk among males via an additive model (OR=0.59, 95% CI=0.39, 0.89). We showed that CCR6 polymorphism was a risk factor among females but a protective factor among males. Functional studies are warranted to unravel the pathophysiological relevance of the gene variant and other linked variants with RA. PMID- 22092174 TI - Neural response to the second stimulus associated with poor speed discrimination performance in schizophrenia. AB - Visual motion processing is compromised in schizophrenia (SZ), but it is uncertain what neural deviations account for their motion analysis abnormalities. Neural activations were measured with dense-array electroencephalography while 14 medicated SZ and 14 healthy persons performed a paired-stimuli forced choice speed discrimination task. SZ had (a) worse-at-speed discrimination, replicating previous findings, (b) normal early extrastriate neural activity (N1) to both motion stimuli, (c) reduced later extrastriate activity (P2) specifically to the second stimulus, and (d) following P2, an enhanced later N2 over parietal cortex. Stronger P2 and N2 responses were associated with better speed discrimination performance across groups. These findings indicate that the neural correlates of poor motion analysis in SZ may not be an early visual analysis abnormality but a problem with efficient use of speed information later in cognitive processing. PMID- 22092175 TI - Antagonistic interaction networks among bacteria from a cold soil environment. AB - Microbial antagonism in an Arctic soil habitat was demonstrated by assessing the inhibitory interactions between bacterial isolates from the same location. Of 139 isolates obtained from five soil samples, 20 antagonists belonging to the genera, Arthrobacter, Pseudomonas and Flavobacterium were identified. Inter-genus, inter species and inter-strain antagonism was observed between the interacting members. The extent of antagonism was temperature dependent. In some cases, antagonism was enhanced at 4 degrees C but suppressed at 18 degrees C while in some the reverse phenomenon was observed. To interpret antagonism from an ecological perspective, the interacting members were delineated according to their positional roles in a theoretical antagonistic network. When only one antimicrobial producer (P) was present, all the other members permitted grouping into either sensitive (S) or resistant (R). Composite interactive types such as PSR, PS, PR or SR could be designated only when at least two producers were present. Mapping of all possible antagonistic interaction networks based on the individual positional roles of the interactive types illustrates the existence of complex and interconnected networks among microbial communities. PMID- 22092176 TI - Actinobacterial community dominated by a distinct clade in acidic soil of a waterlogged deciduous forest. AB - Members of the Actinobacteria are among the most important litter decomposers in soil. The site of a waterlogged deciduous forest with acidic soil was explored for actinobacteria because seasonality of litter inputs, temperature, and precipitation provided contrasting environmental conditions, particularly variation of organic matter quantity and quality. We hypothesized that these factors, which are known to influence decomposition, were also likely to affect actinobacterial community composition. The relationship between the actinobacterial community, soil moisture and organic matter content was assessed in two soil horizons in the summer and winter seasons using a 16S rRNA taxonomic microarray and cloning-sequencing of 16S rRNA genes. Both approaches showed that the community differed significantly between horizons and seasons, paralleling the changes in soil moisture and organic matter content. The microarray analysis further indicated that the actinobacterial community of the upper horizon was characterized by high incidence of the genus Mycobacterium. In both horizons and seasons, the actinobacterial clone libraries were dominated (by 80%) by sequences of a separate clade sharing an ancestral node with Streptosporangineae. This relatedness is supported also by some common adaptations, for example, to soil acidity and periodic oxygen deprivation or dryness. PMID- 22092177 TI - Investigation of the faecal microbiota of kittens: monitoring bacterial succession and effect of diet. AB - Weaning is a stressful process for kittens and is often associated with diarrhoea and the onset of infectious diseases. The gastrointestinal (GI) microbiota plays an essential role in host well-being, including improving homoeostasis. Composition of the GI microbiota of young cats is poorly understood and the impact of diet on the kitten microbiota unknown. The aims of this study were to monitor the faecal microbiota of kittens and determine the effect(s) of diet on its composition. Bacterial succession was monitored in two groups of kittens (at 4 and 6 weeks, and 4 and 9 months of age) fed different foods. Age-related microbial changes revealed significantly different counts of total bacteria, lactic acid bacteria, Desulfovibrionales, Clostridium cluster IX and Bacteroidetes between 4-week- and 9-month-old kittens. Diet-associated differences in the faecal microbiota of the two feeding groups were evident. In general, fluorescence in situ hybridization analysis demonstrated bifidobacteria, Atopobium group, Clostridium cluster XIV and lactic acid bacteria were dominant in kittens. Denaturing gradient gel electrophoresis profiling showed highly complex and diverse faecal microbiotas for kittens, with age- and/or food-related changes seen in relation to species richness and similarity indices. Four-week old kittens harboured more diverse and variable profiles than those of weaned kittens. PMID- 22092178 TI - Characterization and distribution of the gene cluster encoding RumC, an anti Clostridium perfringens bacteriocin produced in the gut. AB - Ruminococcin C (RumC) is a trypsin-dependent bacteriocin produced by Ruminococcus gnavus E1, a gram-positive strict anaerobic strain isolated from human feces. It consists of at least three similar peptides active against Clostridium perfringens. In this article, a 15-kb region from R. gnavus E1 chromosome, containing the biosynthetic gene cluster of RumC was characterized. It harbored 17 open reading frames (called rum(c) genes) with predicted functions in bacteriocin biosynthesis and post-translational modification, signal transduction regulation, and immunity. An unusual feature of the locus is the presence of five genes encoding highly homologous, but nonidentical RumC precursors. The transcription levels of the rum(c) genes were quantified. The rumC genes were found to be highly expressed in vivo, when R. gnavus E1 colonized the digestive tract of mono-contaminated rats, whereas the amount of corresponding transcripts was below detection level when it grew in liquid culture medium. Moreover, the rumC-like genes were disseminated among 10 strains (R. gnavus or related species) previously isolated from human fecal samples and selected for their capability to produce a trypsin-dependant anti-C. perfringens compound. All harbored at least a rumC1-like copy, four exhibited rumC1-5 genes identical to those of strain E1. PMID- 22092179 TI - Optical response of a cyclometalated iridium(III) hydrazino complex to carbon dioxide: generation of a strongly luminescent iridium(III) carbazate. AB - A system pairing the luminescent core of [Ir(ppy)(2)L(2)](+) (ppy = 2 phenylpyridine) with simple hydrazino ancillary ligands (L = N(2)H(4)) has been prepared for the direct optical detection of carbon dioxide (CO(2)). Silver assisted and silver-free techniques were used for the successful introduction of N(2)H(4) into the [Ir(ppy)(2)Cl](2) coordination sphere at room temperature to give the corresponding biscyclometalated iridium(III) hydrazino species as either a CF(3)SO(3)(-) (OTf(-), 2a) or Cl(-) (2b) salt. The silver-free route was accomplished by the direct replacement of the ligated Cl(-) using a slight excess of hydrazine. The luminescence profile of the cationic iridium(III) hydrazino complex 2a (lambda(max) = 501 nm) undergoes a red shift (lambda(max) = 524 nm), accompanied by a change in the peak shape during exposure to CO(2) in solution. The spectral changes observed are attributed to the formation of the corresponding neutral carbazate species Ir(ppy)(2)(H(2)NNHCOO) (3) and are not consistent with protonation of the ligated hydrazine. Conversion of the hydrazino species to the carbazate species is solvent-dependent and irreversible. The hydrazino and carbazate species have been structurally characterized by single crystal X-ray diffraction; both compounds exhibit long-lived and intense room temperature luminescence in solution with tau = 1.56 and 1.80 MUs and phi(em) = 0.42 and 0.45, respectively. PMID- 22092180 TI - Liquid chromatography-coupled tandem mass spectrometry based assay to evaluate inosine-5'-monophosphate dehydrogenase activity in peripheral blood mononuclear cells from stem cell transplant recipients. AB - Combinations of immunosuppressive drugs are routinely used post-transplantation to prevent rejection and/or other complications and optimize outcomes. The prodrug ester mycophenolate mofetil (MMF) is frequently used in solid-organ and stem cell transplantation settings. A growing body of evidence supports therapeutic monitoring of this immunosuppressant to optimize its efficacy and reduce toxicity. Thus, pharmacodynamic monitoring of MMF is a strategy that could potentially improve patient outcomes. Pharmacodynamic measurements require evaluation of inosine-5'-monophosphate dehydrogenase (IMPDH) activity, the target enzyme of the active moiety mycophenolic acid. Various nonradioactive methods using chromatographic separations have been used to quantify xanthosine monophosphate, the catalytic product of the enzyme, to indirectly evaluate IMPDH activity. However, no methods have used mass spectrometry based detection, which provides more specificity and sensitivity. Here, we describe a liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) method for the quantification of xanthosine monophosphate and adenosine monophosphate (for normalization) in lysates of peripheral blood mononuclear cells (PBMCs) from hematopoietic stem cell transplant (HSCT) recipients. Linearity, precision, and accuracy were validated over a large range of concentrations for each compound. The method could measure analytes with high sensitivity, accuracy (93-116%), and reproducibility (CV < 7.5%). Its clinical application was validated in PBMC lysates obtained from healthy individuals (n = 43) and HSCT recipients (n = 19). This reliable and validated LC-MS/MS method could be a useful tool for pharmacodynamic monitoring of patients treated with MMF. PMID- 22092181 TI - Recovery of T1 response following rocuronium induced neuromuscular block reversed by sugammadex. PMID- 22092182 TI - Combined intramedullary and external skeletal fixation of metatarsal and metacarpal fractures in 12 dogs and 19 cats. AB - OBJECTIVE: To report surgical technique, clinical experiences, and long-term outcomes of combined intramedullary/external skeletal fixation of metatarsal (MT) and metacarpal (MC) fractures in dogs and cats. STUDY DESIGN: Case series. ANIMALS: Dogs (n = 12); 19 cats. METHODS: Clinical and radiographic records of animals managed by combined intramedullary/external fixation of MT/MC fractures were reviewed. Signalment, fracture configuration, complications, and subjective clinical findings were recorded. Surgical technique involved retrograde intramedullary pin placement into fractured MT/MC bones, and transverse pin placement in the base of the MT/MCs or tarsal/carpal bones. Contoured pin ends were enshrouded dorsally in epoxy resin and implants maintained until fracture union. Postoperative clinical and radiographic reassessment was performed where possible. RESULTS: Small breed dogs (n = 12) and 19 cats were operated. Fixator removal occurred in < 10 weeks in all cases. Complications included synostosis (n = 2), pin tract discharge (7), excessive postoperative swelling (8), skin abrasions from the frame (2), and paw distortion associated with frame impingement (2). Long-term radiography documented degenerative changes associated with MT-phalangeal or MC-phalangeal joints in 2 dogs; 7 cats, but changes were typically graded mild or moderate and affected only 1 or 2 joints. CONCLUSIONS: Combined intramedullary/external fixation of MT/MC fractures is viable, particularly juxta-articular fractures. Pin penetration of MT-phalangeal or MC phalangeal joints may cause morbidity and requires further study. PMID- 22092186 TI - Cellular immunostimulation by CpG-sequence-coated DNA origami structures. AB - To investigate the potential of DNA origami constructs as programmable and noncytotoxic immunostimulants, we tested the immune responses induced by hollow 30-helix DNA origami tubes covered with up to 62 cytosine-phosphate-guanine (CpG) sequences in freshly isolated spleen cells. Unmethylated CpG sequences that are highly specific for bacterial DNA are recognized by a specialized receptor of the innate immune system localized in the endosome, the Toll-like receptor 9 (TLR9). When incubated with oligonucleotides containing CpGs, immune cells are stimulated through TLR9 to produce and secrete cytokine mediators such as interleukin-6 (IL 6) and interleukin-12p70 (IL-12p70), a process associated with the initiation of an immune response. In our studies, the DNA origami tube built from an 8634 nt long variant of the commonly used single-stranded DNA origami scaffold M13mp18 and 227 staple oligonucleotides decorated with 62 CpG-containing oligonucleotides triggered a strong immune response, characterized by cytokine production and immune cell activation, which was entirely dependent on TLR9 stimulation. Such decorated origami tubes also triggered higher immunostimulation than equal amounts of CpG oligonucleotides associated with a standard carrier system such as Lipofectamine. In the absence of CpG oligonucleotides, cytokine production induced by the origami tubes was low and was not related to TLR9 recognition. Fluorescent microscopy revealed localization of CpG-containing DNA origami structures in the endosome. The DNA constructs showed in contrast to Lipofectamine no detectable toxicity and did not affect the viability of splenocytes. We thus demonstrate that DNA origami constructs represent a delivery system for CpG oligonucleotides that is both efficient and nontoxic. PMID- 22092187 TI - Disease management and medication compliance. AB - Lack of medication compliance is harmful to health care systems from both a clinical and economic perspective. This study examines the methods that disease management organizations employ to identify nonadherent patients and to measure effectiveness of compliance programs for patients with diabetes, hyperlipidemia, and cystic fibrosis. In addition, this study investigates the degree to which disease managers assume risk in their contracts, and whether compliance strategies are being coordinated with payers' use of value-based insurance design, in which patient cost sharing is a function of the relative value of pharmaceuticals. This study's findings suggest that disease management may be falling short in terms of: (a) comprehensive commitment to expert-recommended at home devices used to self-diagnose and measure health indicators; (b) early adoption of expert-recommended new technologies to measure and improve compliance; (c) intensity of use of standard tests in outpatient clinics; (d) coordination of compliance strategies with payers' use of value-based insurance design; and (e) the proportion of risk assumed in disease management contracts. PMID- 22092188 TI - Adherence to preventive recommendations: experience of a cohort presenting for executive health care. AB - Adherence to recommended preventive services and immunizations in adults is suboptimal and often associated with socioeconomic status, race, and access to care. The aim of this study is to evaluate adherence in a cohort without these barriers to ascertain realistically optimal adherence rates and to examine remaining barriers among relatively advantaged individuals. Specifically, it employed a sample of 6889 patients presenting for executive health care from 2005 to 2009. Adherence varied across colorectal cancer screening (79%), mammography (89%), cervical cancer screening (91%), tetanus immunization (82%), and pneumococcal vaccination (62%). Multivariate logistic regressions revealed that age, education, alcohol use concerns, and being married were positively associated with adherence to certain services. Individuals without the usual barriers to care have variable, less-than-ideal rates of adherence to preventive services, which correlate with some health behaviors and demographics. Understanding the predictors of adherence may inform quality improvement processes aimed at optimizing disease prevention. PMID- 22092189 TI - Belt restraint reduction in nursing homes: effects of a multicomponent intervention program. AB - OBJECTIVES: To test the effects of a multicomponent intervention program to reduce the use of belt restraints in psychogeriatric nursing homes. DESIGN: A quasi-experimental longitudinal design. Study duration was 8 months. SETTING: Twenty-six psychogeriatric nursing home wards in 13 Dutch nursing homes were assigned to intervention or control groups. PARTICIPANTS: Seven hundred fourteen residents were selected for participation. Legal representatives of 520 residents agreed on participation; complete data are available for 405 residents. INTERVENTION: The intervention program included four major components: promotion of institutional policy change that discourages use of belt restraint, nursing home staff education, consultation by a nurse specialist aimed at nursing home staff, and availability of alternative interventions. MEASUREMENTS: The primary outcome measure was the frequency of belt restraint use. Secondary outcomes included other types of physical restraints, psychoactive drug use, falls, and fall-related injuries. These data were collected at baseline and after 4 and 8 months. A trained, blinded observer measured the use of belts and other physical restraints types four times during a 24-hour period. RESULTS: The intervention resulted in a 50% decrease in belt use (odds ratio = 0.48, 95% confidence interval = 0.28-0.81; P = .005). No increase occurred in the use of other types of restraints. No marked differences between the groups were found regarding psychoactive drugs, falls, and fall-related injuries. CONCLUSION: A multicomponent intervention program led to a substantial reduction in use of belts, full-enclosure bedrails, and sleep suits without increasing the use of other physical restraints, psychoactive drugs, or falls and fall-related injuries. PMID- 22092190 TI - The compassion of concealment: silence between older caregivers and dying patients in the AIDS era, northwest Tanzania. AB - In northwest Tanzania, where AIDS has been present for 25 years, AIDS-related illness is a trigger through which community members discuss personal experiences of loss and assess social relationships. The terminal phase of AIDS demands intimate social relations between patients and caretakers. In this final phase of illness, caretakers are scrutinised for their behaviour towards the patient. In the moral world in which caregiving takes place, the act of concealing is considered an intrinsic part of proper care. Current debates on morality, stigma and secrecy inform my argument that acts of concealment around dying are not so much related to the exclusion and ostracism of patients but to inclusion and compassionate care. PMID- 22092191 TI - Why humans do not make good vampires. Testing the ability of humans to detect true blood. AB - BACKGROUND: Research indicating the effects of real blood or of its iconic representation on human behaviour has thus far concentrated on phobia and aggressiveness. Little is known about other responses or, more fundamentally, about the biological basis of all such responses. AIM: In this study it is examined whether or not humans are able to detect real blood. METHODS: Human subjects (n = 89) were asked to distinguish different kinds of blood from red control fluids under varying visual and choice conditions. Relevant differences between subjects were tested for through written questionnaires, including standardized scales for disgust sensitivity (DS-R) and blood phobia (MBPI) and performance on two clinical olfactory tests. RESULTS: Analysis of variance shows that humans are excellent detectors of animal blood (in casu pig blood), whereas the ability of detecting human blood is much less developed. Surprisingly, differences in olfactory capacities and personal experience with blood have no effect on blood detection, while blood fear lowers and disgust sensitivity ameliorates this performance. CONCLUSION: This study allows further mapping of the exact role of disgust sensitivity in human behaviour, as well as a deliberate choice of materials in blood-related experiments. It is imperative for further research on the behavioural and psychological impact 'blood' resorts on humans. PMID- 22092192 TI - Resident physician interactions with surrogate decision-makers: the resident experience. AB - This study explored interactions between medical residents and patient surrogates in order to clarify resident understanding of roles and relationships, resident emotional experience, and resident learning processes. Qualitative analysis of in depth interviews were used involving three family medicine residency programs serving culturally diverse, urban, underserved patient populations. Eighteen second- and third-year trainees described a memorable interaction with a surrogate and then were prompted to discuss their learning experience and their role in the interaction. Interviews were transcribed verbatim and analyzed through an iterative process. Residents experienced significant emotional burden during interactions yet continued to value their relationships with surrogates. Despite their reservations about giving recommendations, residents adopted a variety of roles with surrogates as they gave support, information, and advice. Although residents reported little formal education about surrogate decision making, they relied on passive role modeling and their own previous experiences to help surrogates make decisions. Residents have complex and emotionally significant interactions with surrogates despite minimal formal education about surrogate decision-making. Educational efforts should seek to help residents understand their own emotions and the ethical beliefs that underlie the roles they adopt with surrogates. This will help residents to facilitate value-based conversations with surrogates and better support surrogates in the decision making process. PMID- 22092193 TI - Factors influencing the behavior of land applied biosolids. AB - Using biosolids from the Hampton Roads Sanitation District (HRSD), laboratory studies were conducted to provide an insight into the behavior of this material when it is applied on land. The interaction and affinity of the biosolids for heavy metals was determined by packing reactor columns with known amounts of the biosolids and passing through the packed columns aliquots of several heavy metal solutions including, cobalt, copper, lead, iron, manganese, and zinc. The process was repeated until the retention capacity of the columns was reached. Solution parameters were varied to allow investigations of the influence of pH, ionic strength, and inter-elemental effects. The affinity of the biosolids for each metal was determined by calculating the mass of the metal that was adsorbed on the biosolids (removed from the solution) per gram of the biosolids. Using batch and reactor column procedures, samples of the biosolids were fractionated to determine water soluble, exchangeable, adsorbed, organically bound, carbonate, and sulfide fractions and to determine the lability, mobility, and availability of the heavy metal and other contaminants in those fractions. A fractional distribution extraction protocol was specifically conducted for the lead biosolids complex to provide an insight into the lability and bioavailability of the biosolids-bound lead. The affinity of metal ions for the biosolids was found to increase in the order Pb>Fe>Cu>Zn>Ni>Mn>Co. Correspondingly, synergistic effects of the different metals led to characteristic decreases in the respective binding capacities. A decrease in system pH led to a decrease in the binding capacity, a trend that was also observed when the ionic strength increased. Using lead as a model, fractionation studies revealed that adsorption of lead by biosolids is mainly associated with the carbonate fraction. PMID- 22092194 TI - Does a video-interpreting network improve delivery of care in the emergency department? AB - OBJECTIVE: To measure the impact of a policy change from use of telephonic and face-to-face interpreting to use of a video-interpreting network on Emergency Department (ED) care. DATA SOURCES/STUDY SETTING: Observational study of ED care at two California hospitals. STUDY DESIGN: We compared tests ordered, time in the ED, and admission rates for English- and Spanish-speaking patients presenting with chest pain and abdominal pain before and after the policy change. DATA COLLECTION/EXTRACTION METHODS: Data were extracted from electronic medical and billing records. PRINCIPAL FINDINGS: Mean time in the ED, mean number of laboratory tests, radiology services, electrocardiograms, and echocardiograms, and rates of hospital admission for both language groups at both hospitals went down in the post-video-interpreting network period compared with the pre-video interpreting network period. The percentage of patients leaving the ED against medical advice (AMA) increased in one hospital for both language groups; this increase was statistically significantly smaller in the Spanish-language group compared with the English group (p = .04). CONCLUSIONS: The studied video interpreting network had minimal impact on health care outcomes in the ED. PMID- 22092195 TI - Modeling general and specific variance in multifaceted constructs: a comparison of the bifactor model to other approaches. AB - This article recommends an alternative method for testing multifaceted constructs. Researchers often have to choose between two problematic approaches for analyzing multifaceted constructs: the total score approach and the individual score approach. Both approaches can result in conceptual ambiguity. The proposed bifactor model assesses simultaneously the general construct shared by the facets and the specific facets, over and above the general construct. We illustrate the bifactor model by examining the construct of Extraversion as measured by the Revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae, 1992), with two college samples (N = 383 and 378). The analysis reveals that the facets of the NEO-PI-R Extraversion correlate with criteria in opposite directions after partialling out the general construct. The direction of gender differences also varies by facets. Bifactor models combine the advantages but avoid the drawbacks of the 2 existing methods and can lead to greater conceptual clarity. PMID- 22092196 TI - Spatiotemporal organization and thalamic modulation of seizures in the mouse medial thalamic-anterior cingulate slice. AB - PURPOSE: Seizure-like activities generated in anterior cingulate cortex (ACC) are usually classified as simple partial and are associated with changes in autonomic function, motivation, and thought. Previous studies have shown that thalamic inputs can modulate ACC seizure, but the exact mechanisms have not been studied thoroughly. Therefore, we investigated the role of thalamic inputs in modulating ACC seizure-like activities. In addition, seizure onset and propagation are difficult to determine in vivo in ACC. We studied the spatiotemporal changes in epileptiform activity in this cortex in a thalamic-ACC slice to clearly determine seizure onset. METHODS: We used multielectrode array (MEA) recording and calcium imaging to investigate the modulatory effect of thalamic inputs in a thalamic-ACC slice preparation. KEY FINDINGS: Seizure-like activities induced with 4 aminopyridine (4-AP; 250 MUm) and bicuculline (5-50 MUm) in ACC were attenuated by glutamate receptor antagonists, and the degree of disinhibition varied with the dose of bicuculline. Seizure-like activities were decreased with 1 Hz thalamic stimulation, whereas corpus callosum stimulation could increase ictal discharges. Amplitude and duration of cingulate seizure-like activities were augmented after removing thalamic inputs, and this effect was not observed with those induced with elevated bicuculline (50 MUm). Seizure-like activities were initiated in layers II/III and, after thalamic lesions, they occurred mainly in layers V/VI. Two-dimensional current-source density analyses revealed sink signals more frequently in layers V/VI after thalamic lesions, indicating that these layers produce larger excitatory synchronization. Calcium transients were synchronized after thalamic lesions suggesting that ACC seizure-like activities are subjected to desynchronizing modulation by thalamic inputs. Therefore, ACC seizure-like activities are subject to desynchronizing modulation from medial thalamic inputs to deep layer pyramidal neurons. SIGNIFICANCE: Cingulate seizure like activities were modulated significantly by thalamic inputs. Repeated stimulation of the thalamus efficiently inhibited epileptiform activity, demonstrating that the desynchronization was pathway-specific. The clinical implications of deep thalamic stimulation in the modulation of cingulate epileptic activity require further investigation. PMID- 22092197 TI - Investigating the mechanism of substrate uptake and release in the glutamate transporter homologue Glt(Ph) through metadynamics simulations. AB - A homeostatic concentration of glutamate in the synaptic cleft ensures a correct signal transduction along the neuronal network. An unbalance in this concentration can lead to neuronal death and to severe neurodegenerative diseases such as Alzheimer's or Parkinson's. Glutamate transporters play a crucial role in this respect because they are responsible for the reuptake of the neurotransmitter from the synaptic cleft, thus controlling the glutamate concentration. Understanding the molecular mechanism of this transporter can provide the possibility of an exogenous control. Structural studies have shown that this transporter can assume at least three conformations, thus suggesting a pronounced dynamical behavior. However, some intermediate states that lead to the substrate internalization have not been characterized and many aspects of the transporter mechanism still remain unclear. Here, using metadynamics simulations, we investigate the substrate uptake from the synaptic cleft and its release in the intracellular medium. In addition, we focus on the role of ions and substrate during these processes and on the stability of the different conformations assumed by the transporter. The present dynamical results can complement available X-ray data and provide a thorough description of the entire process of substrate uptake, internalization, and release. PMID- 22092198 TI - Comparison of the mechanical behaviors of locked and nonlocked plate/screw fixation applied to experimentally induced rotational osteotomies in canine ilia. AB - OBJECTIVE: To compare the mechanical behaviors of 2 locked (parallel and diverging screws) and 1 nonlocked (NL) version of triple pelvic osteotomy (TPO) plate/screw fixation. STUDY DESIGN: In vitro biomechanical evaluation. ANIMALS: Cadaveric canine hemipelves. METHODS: Comparison 1-NL screws 20 degrees TPO (NL 20) construct versus locked parallel (LP) screws 20 degrees TPO (LP-20) construct (n = 7). Comparison 2-LP-20 construct versus locked diverging (LD) screws 20 degrees TPO (LD-20) construct (n = 6). Condition 1-Nondestructive loading to determine stiffness. Condition 2-Cyclic loading to determine stiffness, screw loosening, and osteotomy gap displacement. Condition 3-Load to failure (yield load, yield displacement, maximum load, load to failure, failure mode). RESULTS: Stiffness was not significantly different for NL-20 versus LP-20 constructs (P = .48) or for LP-20 versus LD-20 constructs (P = .83). Screw loosening was significantly more frequent for NL-20 versus LP-20 (P = .01) and for LD-20 versus LP-20 constructs (P = .02). The relative risk for screw loosening with NL-20 constructs versus LP-20 constructs was 1.4 (95% CI: 1.1 1.8). The relative risk for screw loosening with LD-20 versus LP-20 was 1.6 (95% CI: 1.1-2.2). Yield load was significantly greater for LP-20 versus NL-20 and LD 20 constructs (P = .04, P = .03), respectively. CONCLUSIONS: No TPO constructs tested maintained complete integrity after cyclic loading; however, screw loosening was significantly reduced and yield loads were significantly larger for LP-20 plate/screw constructs. PMID- 22092200 TI - Cognitive impairments after critical illness. AB - BACKGROUND: Cognitive impairments are common after critical illness. Aetiology and effects of cognitive impairments in this setting are not fully revealed. The aim of this study was to investigate the effect of critical illness and intensive care unit (ICU) treatment on cerebral function. METHODS: Adult ICU patients with no previous history of cerebral disorders were included. Non-delirious patients scoring >= 24 on mini-mental state examination on ICU discharge were explored neuropsychologically using the Cambridge Neuropsychological Test Automated Battery (CANTAB) to classify cognitive impairments. Tests were repeated at 3 and 12 months. Results were compared with a normal reference population and a surgical comparison group. RESULTS: We included 55 patients. Eighteen of 28 patients were cognitively impaired, and it was not possible to classify 27 patients. The ICU survivors tested with CANTAB scored significantly lower than the reference population. They also scored worse than a surgical comparison group but significantly on only one of 10 measures. At 3 months follow-up, included patients scored significantly worse on one of 10 reported CANTAB measures. There were no differences at 12 months. We found no associations between age, co morbidity, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment score, presence of cardiovascular disease, duration of ventilatory support and length of ICU stay, and cognitive impairments. Having a cognitive impairment did not affect other outcome measures such as mortality, health related quality of life, and institutionalization. CONCLUSIONS: Cognitive impairments are common after critical illness and may be caused by the critical illness in itself. Incidences are high after ICU discharge (64%) but drops rapidly during the first 3 months after discharge. PMID- 22092201 TI - Risk factors for 1-year mortality in patients with nontraumatic intracranial hemorrhage requiring intensive care. AB - BACKGROUND: Mortality in patients with intracranial hemorrhage remains high. The aim of this study was to determine the 1-year survival and potential risk factors for 1-year mortality in patients with nontraumatic intracranial hemorrhage requiring intensive care. METHODS: This was a 3-year (2005-2007) retrospective study in a university-level intensive care unit (ICU). Patient characteristics, level of consciousness, and radiological findings of the primary head computed tomography were recorded on admission. Sequential Organ Failure Assessment scores were recorded during the ICU stay. Patients were divided into two groups: subarachnoid hemorrhage (SAH) group and intracerebral hemorrhage (ICH) group. Kaplan-Meier survival curves were constructed, and independent risk factors were determined using Cox proportional hazards regression analyses. RESULTS: Two hundred twenty-nine patients were analyzed. The 1-year mortality rate was 32% in patients with SAH and 44% in patients with ICH. The risk factors for 1-year mortality in both groups were unconsciousness on admission [SAH: hazard ratio (HR) 6.2, P = 0.017 and ICH: HR 3.0, P = 0.004] and renal failure during the ICU stay (SAH: HR 2.5, P = 0.021 and ICH: HR 3.6, P = 0.021). Risk factors specific to the type of hemorrhage were the presence of ICH (HR 2.0, P = 0.033) and diffuse cerebral edema (HR 2.3, P = 0.017) in the SAH group and a prior use of warfarin (HR 5.1, P = 0.016) in the ICH group. CONCLUSIONS: In addition to decreased level of consciousness on admission, renal failure during the ICU stay is an independent risk factor for 1-year mortality in nontraumatic SAH as well as ICH. PMID- 22092202 TI - Influence of prone positioning on the measurement of transpulmonary thermodilution-derived variables in critically ill patients. AB - BACKGROUND: Patients with respiratory failure undergoing prone positioning (PP) are often monitored by the transpulmonary thermodilution (TPTD) technique. However, it remains unclear whether the measurement of TPTD-derived variables is influenced by PP. We investigated the effects of 135 degrees PP on the accuracy of TPTD-derived variables and their changes over an 8-10 h period of time. METHODS: We studied 16 mechanically ventilated patients who underwent PP for acute respiratory distress syndrome or acute lung injury and received hemodynamic monitoring by the TPTD technique. Measurements of extravascular lung water index (EVLWI), global end-diastolic volume index (GEDVI), ejection fraction corrected GEDVI (cGEDVI), pulmonary vascular permeability index (PVPI) and hemodynamic variables were obtained 10 min before and after positioning and repositioning. One-way analysis of variance and Friedman's test with Student-Newman-Keuls method for all pairwise multiple comparisons were used for statistical analysis. RESULTS: EVLWI increased after proning (12.7 +/- 4.7 vs. 14.8 +/- 7.8 ml/kg) and remained elevated until end of prone positioning (15.1 +/- 7.2 vs. 12.8 +/- 4.9 ml/kg) with P < 0.05 for difference between respective time points. After proning, GEDVI remained unchanged (571 +/- 153 vs. 593 +/- 152 ml/m2). At the end of prone positioning GEDVI was 610 +/- 55 ml/m2 and decreased after returning to supine to 553 +/- 14 ml/m2. Proning increased cGEDVI from 525 +/- 136 to 570 +/- 11 ml/m2 and repositioning decreased cGEDVI from 558 +/- 116 to 496 +/- 121 ml/m2. No significant changes in PVPI were observed during the study period. CONCLUSIONS: EVLWI and GEDVI measurements are possibly influenced by prone positioning. In spite of statistical significance, the differences in EVLWI and GEDVI are low and presumably of no clinical relevance. PMID- 22092203 TI - Positive end-expiratory pressure-induced changes in end-expiratory lung volume measured by spirometry and electric impedance tomography. AB - BACKGROUND: A bedside tool for monitoring changes in end-expiratory lung volume (DeltaEELV) would be helpful to set optimal positive end-expiratory pressure (PEEP) in acute lung injury/acute respiratory distress syndrome patients. The hypothesis of this study was that the cumulative difference of the inspiratory and expiratory tidal volumes of the first 10 breaths after a PEEP change accurately reflects the change in lung volume following a PEEP alteration. METHODS: Changing PEEP induces lung volume changes, which are reflected in differences between inspiratory and expiratory tidal volumes measured by spirometry. By adding these differences with correction for offset, for the first 10 breaths after PEEP change, cumulative tidal volume difference was calculated to estimate DeltaEELV(VT) ((i-e)) . This method was evaluated in a lung model and in patients with acute respiratory failure during a PEEP trial. In patients, DeltaEELV(VT) ((i-e)) were compared with simultaneously measured changes in lung impedance, by electric impedance tomography (EIT), using calibration vs. tidal volume to estimate changes in DeltaEELV(EIT) . RESULTS: In the lung model, there was close correlation (R(2) = 0.99) between DeltaEELV(VT) ((i-e)) and known lung model volume difference, with a bias of -4 ml and limits of agreement of 42 and -50 ml. In 12 patients, DeltaEELV(EIT) was closely correlated to DeltaEELV(VT) ((i-e)) (R(2) = 0.92), with mean bias of 50 ml and limits of agreement of 131 and -31 ml. Changes in EELV estimated by EIT (DeltaEELV(EIT) ) exceeded measurements by spirometry (DeltaEELV(VT) ((i-e)) ), with 15 (+/-15)%. CONCLUSIONS: We conclude that spirometric measurements of inspiratory-expiratory tidal volumes agree well with impedance changes monitored by EIT and can be used bedside to estimate PEEP-induced changes in EELV. PMID- 22092204 TI - Non-toxic alveolar oxygen concentration without hypoxemia during apnoeic oxygenation: an experimental study. AB - BACKGROUND: Oxygenation without tidal breathing, i.e. apnoeic oxygenation in combination with extracorporeal carbon dioxide removal, might be an option in the treatment of acute respiratory failure. However, ventilation with 100% O2, which is potentially toxic, is considered a prerequisite to ensure acceptable oxygenation. We hypothesized that trapping nitrogen (N2) in the lungs before the start of apnoeic oxygenation would keep the alveolar O2 at a non-toxic level and still maintain normoxaemia. The aim was to test whether a predicted N2 concentration would agree with a measured concentration at the end of an apnoeic period. METHODS: Seven anaesthetized, muscle relaxed, endotracheally intubated pigs (22-27 kg) were ventilated in a randomized order with an inspired fraction of O2 0.6 and 0.8 at two positive end-expiratory pressure levels (5 cm and 10 cm H2O) before being connected to continuous positive airway pressure using 100% O2 for apnoeic oxygenation. N2 was measured before the start of and at the end of the 10-min apnoeic period. The predicted N2 concentration was calculated from the initial N2 concentration, the end-expiratory lung volume, and the anatomical dead space. RESULTS: The mean difference and standard deviation between measured and predicted N2 concentration was -0.5 +/- 2%, P = 0.587. No significant difference in the agreement between measured and predicted N2 concentrations was seen in the four settings. CONCLUSIONS: This study indicates that it is possible to predict and keep alveolar N2 concentration at a desired level and, thus, alveolar O2 concentration at a non-toxic level during apnoeic oxygenation. PMID- 22092205 TI - H-index is a sensitive indicator of academic activity in highly productive anaesthesiologists: results of a bibliometric analysis. AB - BACKGROUND: H-index distinguishes differences in scholarly output across faculty ranks in anaesthesiologists, but whether h-index also identifies differences in other aspects of productivity is unknown. We tested the hypothesis that h-index is an indicator of not only publication record, but also grant funding and mentoring in highly productive US academic anaesthesiologists. METHODS: We conducted an internet analysis of the Foundation for Anesthesia Education and Research Academy of Research Mentors in Anesthesiology (n = 43). Publications, citations, citations per publication, and h-index for each investigator were obtained using the Scopus((r)) . Total grants, active grants, years of funding, and duration of longest funded grant were recorded using the US National Institutes of Health Research Portfolio Online Reporting Tools((r)) . Members were surveyed to identify the number of their career trainees and those who obtained independent funding. RESULTS: The median [IRQ (Interquartile range)] h index of members was 23 [17-32 (8-50)]. Members published 136 [100-225 (39-461)] papers with 3573 [1832-5090 (150-11,601)] citations and 21 [15-32 (4-59)] citations per publication. Members received four [3-7 (0-10)] grants and were funded for 29 [17-45 (0-115)] grant-years. Survey respondents (79%) mentored 40 [26-69 (15-191)] trainees, three [2-6 (0-20)] of which subsequently received funding. Members with h-indices greater than the median had more publications, citations, citations per publication, grants, and years of funding compared with their counterparts. H-index was associated with total citations, active grants, and the number of trainees. CONCLUSIONS: In addition to publication record, h index sensitively indicates grant funding and mentoring in highly productive US academic anaesthesiologists. PMID- 22092206 TI - GlideScope videolaryngoscope vs. Macintosh direct laryngoscope for intubation of morbidly obese patients: a randomized trial. AB - BACKGROUND: Morbidly obese patients are at increased risk of hypoxemia during tracheal intubation because of increased frequency of difficult and impossible intubation and a decreased apnea tolerance. In this study, intubation with the GlideScope videolaryngoscope (GS) was compared with the Macintosh direct laryngoscope (DL) in a group of morbidly obese patients. METHODS: One hundred consecutive patients (body mass index >= 35 kg/m(2) ) scheduled for bariatric surgery were randomized 1 : 1 to intubation with GS (group GS) or DL (group DL). The primary outcome was intubation time. Secondary outcomes were number of attempts, Cormack-Lehane grade, intubation difficulty scale score (IDS), subjective difficulty of intubation, desaturation, airway bleeding, postoperative sore throat, and hoarseness. Group assignment was not blinded. RESULTS: Intubation in group GS and group DL lasted 48 (22-148) and 32 s (17-209), respectively (median (range); P = 0.0001); median difference 11 s (95% confidence interval 6-17). Laryngoscopic views were better in group GS with Cormack-Lehane grades 1/2/3/4 distributed as 35/13/2/0 vs. 23/13/10/4 in group DL (P = 0.003). IDS scores were significantly lower with GS than with DL. No other statistically significant differences were found. Two cases of failed intubation occurred in group DL vs. none in group GS (non-significant). Both patients were intubated with the GlideScope without problems. CONCLUSION: Intubation of morbidly obese patients with GS was slightly slower than with DL. The increased intubation time was of no clinical consequence as no patients became hypoxemic. Both devices generally performed well in the studied population, but the GS provided better laryngoscopic views and decreased IDS scores. PMID- 22092207 TI - High-resolution solid-state manometry of the effect of rocuronium on barrierpressure. AB - BACKGROUND: The pressure in the lower esophageal sphincter (LES) is partly dependent on striated muscles derived from the crural portion of the diaphragm. The effect of neuromuscular blockade on the integrity of the esophagogastric junction is not well studied. We conducted a prospective interventional study to determine the effect of rocuronium on the barrier pressure (LES pressure - intragastric pressure) of the esophagogastric junction. We also studied the effect of positive pressure ventilation on the barrier pressure after neuromuscular blockade with rocuronium. METHODS: Fourteen patients classified as American Society of Anesthesiologists classification system (ASA) I or II (aged 18-75 years) who presented for elective surgery (11 cholecystectomy, 3 inguinal hernia) participated in the study. Esophageal manometry was performed during anesthetization with propofol, fentanyl, and sevoflurane. The LES pressure was studied prior to anesthesia, after anesthesia induction during spontaneous breathing with laryngeal mask airway, after administration of rocuronium (0.6 mg/kg), and during positive pressure ventilation. RESULTS: Muscle relaxation with rocuronium showed no significant changes in barrier pressure when comparing the pressure immediately before rocuronium administration with the pressure obtained after rocuronium administration at the time point of 0% train-of-four (TOF). Conversion to positive pressure ventilation did not change the barrier pressure with inspiration or expiration. The greatest decrease in barrier pressure was measured after inducing anesthesia when comparing pressures during inspiration (P < 0.01). CONCLUSIONS: Neuromuscular blockade with rocuronium and conversion from spontaneous breathing to positive pressure ventilation does not decrease the barrier pressure during anesthesia induction. PMID- 22092208 TI - Effect of patient position and PEEP on hepatic, portal and central venous pressures during liver resection. AB - BACKGROUND: It has been suggested that blood loss during liver resection may be reduced if central venous pressure (CVP) is kept at a low level. This can be achieved by changing patient position but it is not known how position changes affect portal (PVP) and hepatic (HVP) venous pressures. The aim of the study was to assess if changes in body position result in clinically significant changes in these pressures. METHODS: We studied 10 patients undergoing liver resection. Mean arterial pressure (MAP) and CVP were measured using fluid-filled catheters, PVP and HVP with tip manometers. Measurements were performed in the horizontal, head up and head down tilt position with two positive end expiratory pressure (PEEP) levels. RESULTS: A 10 degrees head down tilt at PEEP 5 cm H(2) O significantly increased CVP (11 +/- 3 to 15 +/- 3 mmHg) and MAP (72 +/- 8 to 76 +/- 8 mmHg) while head up tilt at PEEP 5 cm H(2) O decreased CVP (11 +/- 3 to 6 +/- 4 mmHg) and MAP (72 +/- 8 to 63 +/- 7 mmHg) with minimal changes in transhepatic venous pressures. Increasing PEEP from 5 to 10 resulted in small increases, around 1 mmHg in CVP, PVP and HVP. There was no significant correlation between changes in CVP vs. PVP and HVP during head up tilt and only a weak correlation between CVP and HVP by head down tilt. CONCLUSIONS: Changes of body position resulted in marked changes in CVP but not in HVPs. Head down or head up tilt to reduce venous pressures in the liver may therefore not be effective measures to reduce blood loss during liver surgery. PMID- 22092209 TI - Chronic alcoholism increases the induction dose of propofol. AB - BACKGROUND: The present study was designed to investigate the possible effect of chronic alcohol intake on propofol and remifentanil requirements, which was determined by quantifying the 50% (EC(50) ) and 95% (EC(95) ) effective effect site concentrations for propofol and remifentanil at loss of consciousness (LOC) and after a painful stimulus. METHODS: Thirty male patients (alcoholic group; n = 30) with chronic alcoholism and 30 patients (control group; n = 30) with a history of small alcohol intake were anaesthetized with propofol and remifentanil by target-controlled infusion. The predicted drug concentrations and Bispectral Index (BIS) values were recorded at LOC and after no response to painful stimuli. RESULTS: The EC(50) and EC(95) of propofol at LOC in alcoholic group were 3.15 [95% confidence interval (CI), 2.77-3.37] and 4.05 (95% CI, 3.18-5.26) MUg/ml, respectively, and those of the control group were 2.21 (95% CI, 1.92-2.86) and 3.04 (95% CI, 2.45-4.64) MUg/ml, respectively. The EC(50) and EC(95) of remifentanil measured after no response to painful stimuli in the alcoholic group were 3.02 (95% CI, 2.70-3.38) and 4.98 (95% CI, 4.56-5.89) ng/ml, respectively, and those of the control group were 2.95 (95% CI, 2.68-3.33) and 4.86 (95% CI, 4.55-5.92) ng/ml, respectively. The EC(50) and EC(95) values of propofol at LOC in the control group were significantly lower than that of the alcoholic group. CONCLUSIONS: These findings suggest that the induction dose requirements of propofol are increased in alcoholic patients anaesthetized with propofol and remifentanil administered by target controlled infusion. PMID- 22092210 TI - Washout of sevoflurane from the GE Avance and Amingo Carestation anesthetic machines. AB - BACKGROUND: Inhalational anesthetics must be removed from anesthetic machines to prevent malignant hyperthermia (MH) in susceptible patients or to treat MH occurring during inhalational general anesthesia. This study examines the sevoflurane washout from the GE Avance and Amingo CarestationsTM. METHODS: The care stations were contaminated with sevoflurane during general anesthesia. Then, the vaporizer was removed, the CO2 absorber was exchanged against an empty one and the breathing tubes were substituted by clean ones. In the first part, the fresh gas flow was 10 l/min. In the second part, the Advanced Breathing SystemTM (ABSTM), the internal breathing circuit, was replaced by a laundered component. The fresh gas flow was set to 10 l/min for 10 min and to 5 l/min for the following 20 min. RESULTS: In the 25 measurements of the first part, the sevoflurane concentration decreased from a median of 31.60 ppm [interquartile range (IQR) 130.12 ppm] within 22 min in every case to values below 5 ppm and stayed there for the last 8 min of the measuring (P < 0.0001). In the 15 measurements of the second part, the sevoflurane concentration fell from the median of 8.56 ppm (IQR 8.99 ppm) within 5 min to values being significantly below 5 ppm and stayed there for the following 25 min (P < 0.0001). CONCLUSIONS: In case of sudden onset of MH, the Avance or Amingo CarestationTM can stay in place, if the fresh gas flow is increased to 10 l/min or more. To prepare these machines for MH-susceptible patients, the ABSTM should be substituted by a laundered component. PMID- 22092211 TI - Isoflurane decreases death of human embryonic stem cell-derived, transcriptional marker Nkx2.5(+) cardiac progenitor cells. AB - BACKGROUND: Cardiac progenitor cells (CPCs) derived from human embryonic stem cells (hESCs) can multiply and generate cardiomyocytes, offering their tremendous potential for cardiac regenerative therapy. However, poor survival under stressful conditions is a major hurdle in the regeneration. We investigated whether isoflurane-induced preconditioning can increase hESC-derived CPC survival under oxidative stress. METHODS: Undifferentiated hESCs were cultured in suspension with 20% FBS (fetal bovine serum) and 20 ng/ml of BMP-4 (bone morphogenetic protein-4) to form embryoid bodies and grown onto Matrigel-coated plates for 2-3 weeks. To characterise the differentiated CPCs, immunostaining for Nkx2.5 (nonspecific transcriptional marker) and Isl-1 was performed. hESC-derived CPCs were exposed to oxidative stress induced by H(2) O(2) and FeSO(4) . For anaesthetic preconditioning, CPCs were exposed to isoflurane (0.25, 0.5, 1.0 mM). CPC survival was determined by trypan blue exclusion. A mitoK(ATP) channels inhibitor, 5-hydroxydecanoic acid (200 MUM) and an opener, diazoxide (100 MUM), were used to investigate the involvement of mitoK(ATP) channels. RESULTS: hESC derived CPCs stained with Nkx2.5 were 95 +/- 3% of total cell number. Isoflurane (0.5 and 1.0 mM)-preconditioned CPCs showed a significantly lower death rate compared with control (0.5 mM: 30.6 +/- 10.7% and 1.0 mM: 28.5 +/- 6.2% vs. control: 43.2 +/- 9.9%). Inhibition of mitoK(ATP) channels with 5-HD completely abolished the protective effects of isoflurane. Diazoxide significantly decreased CPC death (29.5 +/- 12.4%). However, when diazoxide was applied to CPC preconditioned with isoflurane, CPC death did not decrease further (28.7 +/- 10.9%). CONCLUSION: Isoflurane increased hESC-derived Nkx2.5(+) CPC survival under oxidative stress, and mitoK(ATP) channels may be involved in the protective effect. PMID- 22092212 TI - Plasma tau protein in comatose patients after cardiac arrest treated with therapeutic hypothermia. AB - BACKGROUND: Neurological outcome after cardiac arrest (CA) is difficult to predict in the acute phase. In this pilot study, we assessed blood levels of tau protein as a prognostic marker for the neurological outcome after 6 months in patients treated with hypothermia after resuscitation from CA. METHODS: 22 unconscious patients resuscitated after CA were treated with mild hypothermia (32 34 degrees C) for 26 h. Blood samples were collected at 2, 6, 12, 24, 48, and 96 h after CA, and the concentration of tau protein was analyzed. Neurological outcome was assessed with the Glasgow-Pittsburgh cerebral performance category (CPC) scale at intensive care unit (ICU) discharge and after 6 months. The higher of the two CPC scores was used. RESULTS: At ICU discharge, 21/22 patients were alive, of whom 10 had a good (CPC 1-2) outcome. After 6 months, 15/22 patients were alive, of whom 14 had a good outcome. Tau protein levels were higher among those with a poor outcome at 48 h and 96 h. At 96 h sampling, tau concentration predicted a poor outcome (CPC 3-5) with a sensitivity of 71% and a specificity of 93%. CONCLUSIONS: Although in a pilot study, a late increase in plasma tau protein seems to be associated with a worse outcome after hypothermia treatment after CA, although more studies are needed. PMID- 22092213 TI - Movement-evoked breakthrough cancer pain despite intrathecal analgesia: a prospective series. AB - BACKGROUND: Intrathecal analgesia (ITA) is a valuable treatment option for intractable cancer-related pain. However, the issue of movement-evoked breakthrough pain (BTP) has not been specifically investigated in the ITA setting. The aim of the study was to evaluate the effect of ITA on spontaneous resting pain intensity (SRPI), doses of non-ITA opioids, and specifically on movement-evoked pain intensity (MEPI). METHODS: We prospectively studied 28 consecutive patients who graded SRPI and MEPI on a 0-10 numerical rating scale (NRS) at the time of ITA procedure, after 1 week, and after 1 month. Mild pain was defined as NRS <= 3 and severe pain as NRS >= 7. Concomitant doses of opioids were registered. RESULTS: After 1 week, no patient had severe SRPI compared with 31% before ITA, and the proportion of patients with mild SRPI had increased from 27% to 76%. Meanwhile, the median daily dose of non-ITA opioids decreased from 575 to 120 mg of oral morphine equivalents. The effect on SRPI and on doses of non-ITA opioids remained essentially unchanged during the study month, but the proportion of patients having severe MEPI did not change significantly: 44% still had severe MEPI after 1 week and 40% after 1 month. CONCLUSION: Movement-evoked BTP was a major clinical problem throughout the study month despite otherwise successful ITA. Improving the quality of life of patients with intractable cancer related pain should include developing strategies to better deal with movement evoked BTP. PMID- 22092214 TI - Levosimendan for treatment of septic shock: homeotherapy or inadequate therapy? PMID- 22092217 TI - Gamma oscillation: is there a place in post-operative cognitive dysfunction? PMID- 22092220 TI - Predicting massive blood transfusion using clinical scores post-trauma. AB - BACKGROUND AND OBJECTIVES: Early prediction of massive transfusion (MT) post trauma may reduce mortality by earlier delivery of blood products. A clinical prediction tool (PWH score) for this purpose was developed at the Prince of Wales Hospital, Hong Kong. The aims of this study were to apply this tool to major trauma patients in Victoria, Australia and compare the score to the Assessment of Blood Consumption (ABC) score and the Trauma-Associated Severe Haemorrhage (TASH) score. METHODS: A retrospective review of patients entered into the The Alfred Trauma Registry between January 2006 and December 2009 was conducted. The performance of the PWH score to predict MT defined by 5 units of packed red blood cells in 4 h was compared with the ABC and TASH scores. Included patients presented to the Emergency & Trauma Centre from the scene and had had complete datasets with respect to the components of the three scores. RESULTS: There were 1234 patients included in the study with 195 (15.8%) receiving a MT and an overall mortality of 14.0%. The PWH score had an area under the receiver operating characteristics (ROC) curve of 0.842 (95% CI: 0.820-0.862). The area under the ROC curve of the PWH score was significantly less than that of the TASH score (chi(2)=19.8, P<0.001) and significantly greater than that of the ABC score (chi(2)=9.3, P=0.002). CONCLUSIONS: The PWH score performs with similar accuracy when applied to an Australian population as in its derivation population. The relative simplicity of the PWH score makes it a viable tool for clinical use, although utility of such tools may be more suited for research in determining inclusion or exclusion criteria for comparative outcome studies. PMID- 22092221 TI - Evaluation of sublingual microcirculatory blood flow in the critically ill. AB - BACKGROUND: The microcirculation regulates the supply of oxygen and nutrients to tissues. The sublingual region is frequently used as a window to microcirculation in critically ill patients. Numerous studies have reported impaired sublingual microcirculatory flow. We hypothesized that the quality of sidestream dark field imaging (SDF) recordings could be systematically analyzed to justify the monitoring of sublingual microcirculation in interventional studies or in clinical practice. METHODS: The sublingual microcirculation in critically ill patients with septic shock, open heart surgery, or alcoholic pancreatitis, and healthy subjects was recorded with a hand held SDF device by one trained investigator in observational setting. A total of 82 video recording sessions were performed and 240 video clips eligible for quality assessment were identified. Quality assessment was performed offline by two investigators independently and blinded for the origin of the video file. RESULTS: Of the 240 clips, pressure artifact was detected in 86 (36%), major blood in 5 (2.1%), major saliva in 21 (8.8%) and extreme brightness causing loss of visible capillaries in 16 (6.7%) clips. The dominating vessel architecture was multiple size vessels in 228 (95%) and repeating capillary loop motif in 12 (5.0%). The mean (+/- SD) relative size reduction during stabilization was -6.9% (+/- 4.7%). Excellent technical quality was detected in 74 of 240 (30.8%) recordings. CONCLUSIONS: Our findings highlight the need of a comprehensive training period and reporting of data quality before findings with SDF imaging can be accepted as surrogate end points in interventional studies or as guidance in clinical practice. PMID- 22092222 TI - Composite QDs@MIP nanospheres for specific recognition and direct fluorescent quantification of pesticides in aqueous media. AB - Quantum dots (QDs)-based molecularly imprinted polymer (MIP) composite nanospheres were successfully prepared via a facile and versatile ultrasonication assisted encapsulation method. Unlike the hydrogen-bond-based MIPs, these so prepared QDs-MIP composite nanospheres, relying on the interaction including van der Waals forces and hydrophobic forces, demonstrated excellent selectivity in aqueous media. Their small particle sizes and carboxyl-enriched polymer matrixes give rise to their good dispersibility and stability in aqueous solution, and faster adsorption and desorption kinetics, which further make them extensively applicable for chemical/biological sensors in aqueous media. Based on the fluorescence quenching via template analytes (diazinon) rebinding into the recognition cavities in the polymer matrixes, the QDs-MIP nanospheres were successfully applied to the direct fluorescence quantification of diazinon, independent of extracting templates from the MIP nanospheres, as well as further complicated and time-consuming assays. This novel method can selectively and sensitively detect down to 50 ng/mL of diazinon in water, and a linear relationship has been obtained covering the concentration range of 50-600 ng/mL. The present studies provide a new and general strategy to fabricate other multifunctional (luminescent and magnetic) inorganic-organic MIP nanocomposites with highly selective recognition ability in aqueous media and are pretty desirable for biomedical/chemical sensing applications. PMID- 22092223 TI - Isotope fractionation in aqua-gas systems: Cl(2)-HCl-Cl(-), Br(2)-HBr-Br(-) and H(2)S-S(2-). AB - We report calculated values of isotope fractionation factors between chlorine, bromine and sulphide hydrated anions and respective gaseous compounds: hydrogen chloride, hydrogen bromide, molecular chlorine and bromine and hydrogen sulphide. For the calculation of the reduced partition function ratios (beta-factors) of hydrated Cl(-), Br(-) and S(2-) anions, we used a model of a cluster composed of the considered ion surrounded by two shells of H(2)O molecules. Only the electrostatic interaction between ion and water molecules treated as electric dipoles was taken into account. The beta-factors for the gaseous compounds (HCl, Cl(2), HBr, Br(2) and H(2)S) were calculated from vibrational frequencies reported by Urey and Greiff [Isotopic Exchange Equilibria, J. Am. Chem. Soc. 57, 321 (1935)] and Schauble et al. [Theoretical Estimates Equilibrium Chlorine Isotope Fractionation, Geochim. Cosmochim. Acta 67, 3267 (2003)]. Low-temperature isotope fractionation between chlorine-hydrated anion and hydrogen chloride attains 1.55-1.680/00 (this work), which is in good agreement with experimental data (1.4-1.80/00) [Z.D. Sharp, J.D. Barnes, T.P. Fischer and M. Halick, An Experimental Determination of Chlorine Isotope Fractionation in Acid Systems and Applications to Volcanic Fumaroles, Geochim. Cosmochim. Acta 74, 264 (2010)]. The predicted isotope fractionations for hydrated bromine and HBr, Br(2) gases are very small, 1000 ln alpha, do not exceed 0.80/00; thus, the expected variations of bromine isotope composition in aqua-gas systems will require enhanced precision for their detection. In contrast, the sulphur isotope fractionation between H(2)S( gas ) and S(2-) attains 6.00/00 at room temperature and drops nearly linearly to 3.10/00 at 350 degrees C. PMID- 22092224 TI - Magnetic resonance volumetry and spectroscopy of hippocampus and insula in relation to severe exposure of traumatic stress. AB - Severe and chronic stress affects the hippocampus, especially during development. However, studies concerning structural alterations of the hippocampus yielded a rather inconsistent picture. Moreover, further anxiety-relevant brain regions, such as the insula, might be implicated in the pathophysiology of posttraumatic stress disorder (PTSD). We combined magnetic resonance (MR) volumetric and spectroscopic analyses of hippocampus and insula in highly traumatized refugees without a history of alcohol/substance abuse or other comorbid diseases. No PTSD related difference was apparent in the volumes or neurometabolite levels of bilateral hippocampus or insula. However, an association between left hippocampal N-acetyl-aspartate (NAA) and adverse childhood experiences indicated a potential detrimental effect of the early environment on hippocampal integrity. Our results add to increasing evidence that PTSD-related, morphological alterations in the hippocampus are a consequence of early adversity or may result from other factors, such as extensive use of alcohol. PMID- 22092225 TI - Health services research and global health. PMID- 22092226 TI - Does HIV services decentralization protect against the risk of catastrophic health expenditures?: some lessons from Cameroon. AB - OBJECTIVE: Scaling up antiretroviral treatment (ART) through decentralization of HIV care is increasingly recommended as a strategy toward ensuring equitable access to treatment. However, there have been hitherto few attempts to empirically examine the performance of this policy, and particularly its role in protecting against the risk of catastrophic health expenditures (CHE). This article therefore seeks to assess whether HIV care decentralization has a protective effect against the risk of CHE associated with HIV infection. DATA SOURCE AND STUDY DESIGN: We use primary data from the cross-sectional EVAL-ANRS 12-116 survey, conducted in 2006-2007 among a random sample of 3,151 HIV-infected outpatients followed up in 27 hospitals in Cameroon. DATA COLLECTION AND METHODS: Data collected contain sociodemographic, economic, and clinical information on patients as well as health care supply-related characteristics. We assess the determinants of CHE among the ART-treated patients using a hierarchical logistic model (n = 2,412), designed to adequately investigate the separate effects of patients and supply-related characteristics. PRINCIPAL FINDINGS: Expenditures for HIV care exceed 17 percent of household income for 50 percent of the study population. After adjusting for individual characteristics and technological level, decentralization of HIV services emerges as the main health system factor explaining interclass variance, with a protective effect on the risk of CHE. CONCLUSION: The findings suggest that HIV care decentralization is likely to enhance equity in access to ART. Decentralization appears, however, to be a necessary but insufficient condition to fully remove the risk of CHE, unless other innovative reforms in health financing are introduced. PMID- 22092227 TI - A proposed framework for understanding the forces behind legislation of universal health insurance: lessons from ten countries. AB - OBJECTIVE: To understand the forces propelling countries to legislate universal health insurance. DATA SOURCE/STUDY DESIGN: Descriptive review and exploratory synthesis of historic data on economic, geographic, socio-demographic, and political factors. DATA EXTRACTION METHODS: We searched under "insurance, health" on MEDLINE and Google Scholar, and we reviewed relevant books and articles via a snowball approach. PRINCIPAL FINDINGS: Ten countries with universal health insurance were studied. For the five countries that passed final universal insurance laws prior to 1958, we found that two forces of "historical context" (i.e., social solidarity and historic patterns), one "ongoing dynamic force" (political pressures), and "one uniqueness of the moment" force (legislative permissiveness) played a major role. For the five countries that passed final legislation between 1967 and 2010, the predominant factors were two "ongoing dynamic forces" (economic pressures and political pressures) and one "uniqueness of the moment" force (leadership). In general, countries in the former group made steady progress, whereas those in the latter group progressed in abrupt leaps. CONCLUSIONS: The lessons of more recent successes-almost all of which were achieved via abrupt leaps-strongly indicate the importance of leadership in taking advantage of generalized economic and political pressures to achieve universal health insurance. PMID- 22092228 TI - Organizational culture and its relationship with hospital performance in public hospitals in China. AB - OBJECTIVE: To measure perceptions of organizational culture among employees of public hospitals in China and to determine whether perceptions are associated with hospital performance. DATA SOURCES: Hospital, employee, and patient surveys from 87 Chinese public hospitals conducted during 2009. STUDY DESIGN: Developed and administered a tool to assess organizational culture in Chinese public hospitals. Used factor analysis to create measures of organizational culture. Analyzed the relationships between employee type and perceptions of culture and between perceptions of culture and hospital performance using multivariate models. PRINCIPAL FINDINGS: Employees perceived the culture of Chinese public hospitals as stronger in internal rules and regulations, and weaker in empowerment. Hospitals in which employees perceived that the culture emphasized cost control were more profitable and had higher rates of outpatient visits and bed days per physician per day but also had lower levels of patient satisfaction. Hospitals with cultures perceived as customer-focused had longer length of stay but lower patient satisfaction. CONCLUSIONS: Managers in Chinese public hospitals should consider whether the culture of their organization will enable them to respond effectively to their changing environment. PMID- 22092229 TI - Functional torque ratios and torque curve analysis of shoulder rotations in overhead athletes with and without impingement symptoms. AB - In this study, we evaluated the peak torque, functional torque ratios, and torque curve profile of the shoulder rotators in overhead athletes with impingement symptoms so as to examine possible alterations in response to sports training and shoulder pain. Twenty-one overhead athletes with impingement symptoms were compared with 25 overhead athletes and 21 non-athletes, none of whom were symptomatic for impingement. The participants performed five maximal isokinetic concentric and eccentric contractions of medial and lateral shoulder rotations at 1.57 rad . s(-1) and 3.14 rad . s(-1). Isokinetic peak torque was used to calculate the eccentric lateral rotation-to-concentric medial rotation and the eccentric medial rotation-to-concentric lateral rotation ratios. An analysis of the torque curve profiles was also carried out. The eccentric lateral rotation-to concentric medial rotation torque ratio of asymptomatic athletes was lower than that of non-athletes at both test velocities. The concentric medial rotation isokinetic peak torque of the asymptomatic athletes, at 3.14 rad . s(-1), was greater than that of the non-athletes, and the peak appeared to occur earlier in the movement for athletes than non-athletes. These findings suggest that there may be adaptations to shoulder function in response to throwing practice. The eccentric medial rotation-to-concentric lateral rotation torque ratio was altered neither by the practice of university-level overhead sports nor impingement symptoms. PMID- 22092230 TI - Identification of heptapeptides interacting with IFN-alpha-sensitive CML cells. AB - BACKGROUND: Interferon-alpha (IFN-alpha) is the traditional therapeutic agent for chronic myeloid leukemia (CML). The molecular mechanism of IFN-alpha efficacy in the treatment of CML is not fully clear. OBJECTIVES: To identify the peptides and/or proteins that bind to the proteins specifically expressed on the surface of IFN-alpha-sensitive CML cells by using a phage display library. DESIGN/METHODS: IFN-alpha-sensitive KT-1/A3 cells were used as the target, and IFN-alpha-resistant subline KT-1/A3R was used as absorber for phage display biopanning. The positive phage clones were identified by enzyme-linked immunosorbent assay and flow cytometry. The peptides were deduced from their DNA sequences. RESULTS: Multiple clones showed high binding efficiency to KT-1/A3 cells compared with that of the other leukemia cells. One of the peptides, KLWVIPQ, has a partial amino acid sequence homology with the C-terminal domain of E3 ubiquitin-protein ligase. CONCLUSIONS: This study presents the identification of specific heptapeptides that bind to IFN-alpha-sensitive KT-1/A3 cells. The cancer-selective ligands provide novel strategies for early and differential diagnoses, as well as potential targeted drug delivery. PMID- 22092231 TI - A prospective cohort study of geriatric syndromes among older medical patients admitted to acute care hospitals. AB - OBJECTIVES: To identify the prevalence of geriatric syndromes in the premorbid for all syndromes except falls (preadmission), admission, and discharge assessment periods and the incidence of new and significant worsening of existing syndromes at admission and discharge. DESIGN: Prospective cohort study. SETTING: Three acute care hospitals in Brisbane, Australia. PARTICIPANTS: Five hundred seventy-seven general medical patients aged 70 and older admitted to the hospital. MEASUREMENTS: Prevalence of syndromes in the premorbid (or preadmission for falls), admission, and discharge periods; incidence of new syndromes at admission and discharge; and significant worsening of existing syndromes at admission and discharge. RESULTS: The most frequently reported premorbid syndromes were bladder incontinence (44%), impairment in any activity of daily living (ADL) (42%). A high proportion (42%) experienced at least one fall in the 90 days before admission. Two-thirds of the participants experienced between one and five syndromes (cognitive impairment, dependence in any ADL item, bladder and bowel incontinence, pressure ulcer) before, at admission, and at discharge. A majority experienced one or two syndromes during the premorbid (49.4%), admission (57.0%), or discharge (49.0%) assessment period. The syndromes with a higher incidence of significant worsening at discharge (out of the proportion with the syndrome present premorbidly) were ADL limitation (33%), cognitive impairment (9%), and bladder incontinence (8%). Of the syndromes examined at discharge, a higher proportion of patients experienced the following new syndromes at discharge (absent premorbidly): ADL limitation (22%); and bladder incontinence (13%). CONCLUSION: Geriatric syndromes were highly prevalent. Many patients did not return to their premorbid function and acquired new syndromes. PMID- 22092232 TI - Postoperative opioid consumption and its relationship to cognitive function in older adults with hip fracture. AB - OBJECTIVES: To determine the relationship between opioid consumption and cognitive impairment after hip fracture repair. DESIGN: Prospective study of consecutive patients. SETTING: Johns Hopkins Bayview Medical Center, Baltimore, Maryland. PARTICIPANTS: Two hundred thirty-six participants aged 65 and older undergoing hip fracture repair. MEASUREMENTS: Older adults without preoperative delirium who underwent hip fracture repair between April 2005 and July 2009 were followed for pain, opioid consumption, and postoperative delirium. Participants were tested for delirium using the Confusion Assessment Method preoperatively and midmorning on Postoperative Day 2. The nursing staff assessed pain on a numeric oral scale (range 0-10). Opioid analgesia was provided in response to pain at rest to achieve scores of 3 or less. Opioid consumption was analyzed with respect to the occurrence of incident postoperative delirium, presence of dementia, and other demographic variables. RESULTS: Of the 236 participants, 66 (28%) had dementia, and 213 (90%) received opioids postoperatively, including 55 (83%) with dementia and 158 (93%) without. There was no association between the use of any postoperative opioid and incident delirium (P = .61) in participants with (P = .33) and without (P = .40) dementia. Dementia, but not postoperative delirium, was associated with less opioid use (P < .001 for dementia; P = .12 for delirium; P = .04, for their interaction; Wald chi-square = 142.8, df = 7). Opioid dose (P >= .59) on Postoperative Days 1 and 2 was not predictive of incident delirium. Dementia (P < .001) and intensive care unit admission (P = .006), not opioid consumption, were the most important predictors of incident postoperative delirium. CONCLUSION: Concern for postoperative delirium should not prevent the use of opioid analgesic therapy sufficient to achieve a generally accepted level of comfort in individuals with or without preexisting cognitive impairment. PMID- 22092233 TI - Mechanical testing of orthopedic suture material used for extra-articular stabilization of canine cruciate ligament-deficient stifles. AB - OBJECTIVE: To determine (1) if braided, polyblend orthopedic suture materials are mechanically superior to monofilament nylon leader and (2) have mechanical properties similar to biomechanical properties of the canine cruciate ligament. SAMPLE POPULATION: Different suture material types. METHODS: Mechanical testing was performed on 5 different orthopedic suture materials: 80# test Mason monofilament nylon leader (MNL), FiberTape (FT), FiberWire (FW), Xgen OrthoFiber (XOF), and LigaFiba (LF) using a servohydraulic materials-testing machine. Materials were loaded to failure while collecting data for tensile strength, load at 3 mm and 5 mm of elongation and stiffness. Cyclic elongation of each suture material was tested under physiologic loading between 70 and 150 N for 1000 cycles using 3 mm of elongation to describe excessive elongation. Load at 3 mm of elongation and performance during cyclic testing were compared to previously published physiologic loads in the dog stifle. RESULTS: Ultimate tensile strength was greatest with LF, followed by XOF that was stronger than FT and FW, and the weakest was MNL. LF was the stiffest of all tested materials at 3 mm of elongation. Cyclic elongation was greatest for the MNL elongating 3.75 mm after 1000 cycles. All polyblend braided materials continued to elongate throughout the 1000 cycles under physiologic loads. CONCLUSIONS: Polyblend suture materials are stronger and elongate less than MNL in pure tension. The mechanical performance of all sutures tested is questionable when compared with the mechanical demands of the normal stifle in a mid-sized dog. PMID- 22092234 TI - Not at all so hard-to-reach: same-sex attracted men in Dar es Salaam. AB - Based on research in Tanzania, this paper critically examines the widely circulating notion that African same-sex attracted men are hard-to-reach individuals and populations. Despite expectations to the contrary, it was neither time consuming nor difficult to identify and get to know same-sex attracted men in Dar es Salaam. On the contrary, a large and diverse group of such men could readily be encountered, befriended and involved in HIV-related research. The fieldwork was characterised by communicative openness and the researcher was treated with immense kindliness, hospitality and inclusivity. While we may not be in a position to say that the situation is identical everywhere else, we find reason to caution against accepting and propagating unexplained, unexamined and unverified claims to the effect that same-sex attracted men in Africa cannot be reached. We argue that such claims contribute to stigmatise same-sex attracted men and to hinder much-needed HIV-related research and programming. PMID- 22092235 TI - Electrically bistable properties of layer-by-layer assembled multilayers based on protein nanoparticles. AB - Electrochemical properties of redox proteins, which can cause the reversible changes in the resistance according to their redox reactions in solution, are of the fundamental and practical importance in bioelectrochemical applications. These redox properties often depend on the chemical activity of transition metal ions as cofactors within the active sites of proteins. Here, we demonstrate for the first time that the reversible resistance changes in dried protein films based on ferritin nanoparticles can be caused by the externally applied voltage as a result of charge trap/release of Fe(III)/Fe(II) redox couples. We also show that one ferritin nanoparticle of about 12 nm size can be operated as a nanoscale memory device, and furthermore the layer-by-layer assembled protein multilayer devices can be extended to bioinspired electronics with adjustable memory performance via molecular level manipulation. PMID- 22092237 TI - Metal-mediated affinity and orientation specificity in a computationally designed protein homodimer. AB - Computationally designing protein-protein interactions with high affinity and desired orientation is a challenging task. Incorporating metal-binding sites at the target interface may be one approach for increasing affinity and specifying the binding mode, thereby improving robustness of designed interactions for use as tools in basic research as well as in applications from biotechnology to medicine. Here we describe a Rosetta-based approach for the rational design of a protein monomer to form a zinc-mediated, symmetric homodimer. Our metal interface design, named MID1 (NESG target ID OR37), forms a tight dimer in the presence of zinc (MID1-zinc) with a dissociation constant <30 nM. Without zinc the dissociation constant is 4 MUM. The crystal structure of MID1-zinc shows good overall agreement with the computational model, but only three out of four designed histidines coordinate zinc. However, a histidine-to-glutamate point mutation resulted in four-coordination of zinc, and the resulting metal binding site and dimer orientation closely matches the computational model (Calpha rmsd = 1.4 A). PMID- 22092238 TI - Distinct white matter abnormalities in different idiopathic generalized epilepsy syndromes. AB - PURPOSE: By definition idiopathic generalized epilepsy (IGE) is not associated with structural abnormalities on conventional magnetic resonance imaging (MRI). However, recent quantitative studies suggest white and gray matter alterations in IGE. The purpose of this study was to investigate whether there are white and/or gray matter structural differences between controls and two subsets of IGE, namely juvenile myoclonic epilepsy (JME) and IGE with generalized tonic-clonic seizures only (IGE-GTC). METHODS: We assessed white matter integrity and gray matter volume using diffusion tensor tractography-based analysis of fractional anisotropy and voxel-based morphometry, respectively, in 25 patients with IGE, all of whom had experienced generalized tonic-clonic convulsions. Specifically, 15 patients with JME and 10 patients with IGE-GTC were compared to two groups of similarly matched controls separately. Correlations between total lifetime generalized tonic-clonic seizures and fractional anisotropy were investigated for both groups. KEY FINDINGS: Tractography revealed lower fractional anisotropy in specific tracts including the crus of the fornix, body of corpus callosum, uncinate fasciculi, superior longitudinal fasciculi, anterior limb of internal capsule, and corticospinal tracts in JME with respect to controls, whereas there were no fractional anisotropy differences in IGE-GTC. No correlation was found between fractional anisotropy and total lifetime generalized tonic-clonic seizures for either JME or IGE-GTC. Although false discovery rate-corrected voxel based morphometry (VBM) showed no gray matter volume differences between patient and control groups, spatial extent cluster-corrected VBM analysis suggested a trend of gray matter volume reduction in frontal and central regions in both patient groups, more lateral in JME and more medial in IGE-GTC. SIGNIFICANCE: The findings support the idea that the clinical syndromes of JME and IGE-GTC have unique anatomic substrates. The fact that the primary clinical difference between JME and IGE-GTC is the occurrence of myoclonus in the former raises the possibility that disruption of white matter integrity may be the underlying mechanism responsible for myoclonus in JME. The cross-sectional study design and relatively small number of subjects limits the conclusions that can be drawn here; however, the absence of a correlation between fractional anisotropy and lifetime seizures is suggestive that the white matter abnormalities observed in JME may not be secondary to seizures. PMID- 22092239 TI - Expanding the safety net of specialty care for the uninsured: a case study. AB - OBJECTIVE: To describe core principles and processes in the implementation of a navigated care program to improve specialty care access for the uninsured. STUDY SETTING: Academic researchers, safety-net providers, and specialty physicians, partnered with hospitals and advocates for the underserved to establish Project Access-New Haven (PA-NH). PA-NH expands access to specialty care for the uninsured and coordinates care through patient navigation. STUDY DESIGN: Case study to describe elements of implementation that may be relevant for other communities seeking to improve access for vulnerable populations. PRINCIPAL FINDINGS: Implementation relied on the application of core principles from community-based participatory research (CBPR). Effective partnerships were achieved by involving all stakeholders and by addressing barriers in each phase of development, including (1) assessment of the problem; (2) development of goals; (3) engagement of key stakeholders; (4) establishment of the research agenda; and (5) dissemination of research findings. CONCLUSIONS: Including safety net providers, specialty physicians, hospitals, and community stakeholders in all steps of development allowed us to respond to potential barriers and implement a navigated care model for the uninsured. This process, whereby we integrated principles from CBPR, may be relevant for future capacity-building efforts to accommodate the specialty care needs of other vulnerable populations. PMID- 22092240 TI - Potential ecological risks of thermal-treated waste recombination DNA discharged into an aquatic environment. AB - It has been shown that thermal-treatment at 100 degrees C can denature deoxyribonucleic acid (DNA), yet this does not cause it to break down completely. To clarify the risk of gene pollution from thermal-treated recombinant DNA, the renaturation characteristics of thermal-denatured plasmid pET-28b and its persistence in aquatic environments were investigated. The results revealed that the double-stranded structure and transforming activity of the thermal-treated plasmid DNA could be recovered even if the thermal-treatment was conducted at 120 degrees C. The presence of sodium chloride (NaCl) and ethylenediamine tetraacetic acid (EDTA) led to the increase of renaturation efficiency of the denatured DNA. When thermal-treated plasmid DNA was discharged into simulated aquatic environments with pH values from 5 to 9, it showed a longer persistence at pH 7 and 8 than that at 5, 6 and 9; however, the denatured plasmid DNA could persist for more than 33 min at any pH. Moreover, a higher ionic strength further protected the thermal-denatured plasmids from degradation in the simulated aquatic environment. These results indicated that when the thermal-treated DNA was discharged into an aquatic environment, it might not break down completely in a short period. Therefore, there is the potential for the discarded DNA to renature and transform, which might result in gene pollution. PMID- 22092241 TI - Allergic reaction after dextran. PMID- 22092242 TI - The transcriptome of the arbuscular mycorrhizal fungus Glomus intraradices (DAOM 197198) reveals functional tradeoffs in an obligate symbiont. AB - * The arbuscular mycorrhizal symbiosis is arguably the most ecologically important eukaryotic symbiosis, yet it is poorly understood at the molecular level. To provide novel insights into the molecular basis of symbiosis-associated traits, we report the first genome-wide analysis of the transcriptome from Glomus intraradices DAOM 197198. * We generated a set of 25,906 nonredundant virtual transcripts (NRVTs) transcribed in germinated spores, extraradical mycelium and symbiotic roots using Sanger and 454 sequencing. NRVTs were used to construct an oligoarray for investigating gene expression. * We identified transcripts coding for the meiotic recombination machinery, as well as meiosis-specific proteins, suggesting that the lack of a known sexual cycle in G. intraradices is not a result of major deletions of genes essential for sexual reproduction and meiosis. Induced expression of genes encoding membrane transporters and small secreted proteins in intraradical mycelium, together with the lack of expression of hydrolytic enzymes acting on plant cell wall polysaccharides, are all features of G. intraradices that are shared with ectomycorrhizal symbionts and obligate biotrophic pathogens. * Our results illuminate the genetic basis of symbiosis related traits of the most ancient lineage of plant biotrophs, advancing future research on these agriculturally and ecologically important symbionts. PMID- 22092243 TI - Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris. AB - BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). OBJECTIVES: To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. METHODS: We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. RESULTS: Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. CONCLUSIONS: The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus. PMID- 22092244 TI - Chronicle of a death foretold: Plasmodium liver stage parasites decide on the fate of the host cell. AB - Protozoan parasites of the genus Plasmodium are the causative agents of malaria. Despite more than 100 years of research, the complex life cycle of the parasite still bears many surprises and it is safe to say that understanding the biology of the pathogen will keep scientists busy for many years to come. Malaria research has mainly concentrated on the pathological blood stage of Plasmodium parasites, leaving us with many questions concerning parasite development within the mosquito and during the exo-erythrocytic stage in the vertebrate host. After the discovery of the Plasmodium liver stage in the middle of the last century, it remained understudied for many years but the realization that it represents a promising target for vaccination approaches has brought it back into focus. The last decade saw many new and exciting discoveries concerning the exo-erythrocytic stage and in this review we will discuss the highlights of the latest developments in the field. PMID- 22092245 TI - An assessment of patient-based and practice infrastructure-based measures of the patient-centered medical home: do we need to ask the patient? AB - OBJECTIVE: To examine the importance of patient-based measures and practice infrastructure measures of the patient-centered medical home (PCMH). DATA SOURCES: A total of 3,671 patient surveys of 202 physicians completing the American Board of Internal Medicine (ABIM) 2006 Comprehensive Care Practice Improvement Module and 14,457 patient chart reviews from 592 physicians completing ABIM's 2007 Diabetes and Hypertension Practice Improvement Module. METHODOLOGY: We estimated the association of patient-centered care and practice infrastructure measures with patient rating of physician quality. We then estimated the association of practice infrastructure and patient rating of care quality with blood pressure (BP) control. RESULTS: Patient-centered care measures dominated practice infrastructure as predictors of patient rating of physician quality. Having all patient-centered care measures in place versus none was associated with an absolute 75.2 percent increase in the likelihood of receiving a top rating. Both patient rating of care quality and practice infrastructure predicted BP control. Receiving a rating of excellent on care quality from all patients was associated with an absolute 4.2 percent improvement in BP control. For reaching the maximum practice-infrastructure score, this figure was 4.5 percent. CONCLUSION: Assessment of physician practices for PCMH qualification should consider both patient based patient-centered care measures and practice infrastructure measures. PMID- 22092247 TI - Re: Preoperative stenting decreases operative time and reoperative rates of ureteroscopy (from: Chu L, Sternberg KM, Averch TD. Preoperative stenting decreases operative time and reoperative rates of ureteroscopy. J Endourol 2011;25:751-754). PMID- 22092248 TI - The acute effects of intranasal oxytocin on automatic and effortful attentional shifting to emotional faces. AB - Oxytocin is known to promote social affiliation. The mechanism by which this occurs is unknown, but it may involve changes in social information processing. In a placebo-controlled study, we examined the influence of intranasal oxytocin on effortful and automatic attentional shifting in 57 participants using a spatial cueing task with emotional and neutral faces. For effortful processing, oxytocin decreased the speed of shifting attention to sad faces presented for 750 ms and facilitated disengagement from right hemifield sad and angry faces presented for 200 ms. For automatic processing, symptoms of depression moderated the relationship between drug and disengagement. Oxytocin attenuated an attentional bias to masked angry faces on disengagement trials in persons with high depression scores. Oxytocin's influence on social behavior may occur, in part, by eliciting flexible attentional shifting in the early stages of information processing. PMID- 22092249 TI - Stable isotope fractionation related to technically enhanced bacterial sulphate degradation in lignite mining sediments. AB - A mine dump aquifer in the Lusatian lignite mining district, Germany, is contaminated with acid mine drainage (AMD). The only natural process that can counteract the effects of the contamination is bacterial sulphate reduction. The technical measures chosen to handle the contamination include the injection of glycerol into the aquifer to supply electron donors and to accelerate the growth and activity of sulphate-reducing bacteria. An initial assessment of the hydrochemical conditions in the aquifer showed that sulphate concentrations are subject to alteration due to flow-related processes. Consequently, the decision whether sulphate reduction is occurring in the investigated aquifer section was based on the stable isotopic composition of dissolved sulphate and sulphide, which were used in combination with sulphate concentrations. The significant enrichment of both heavy sulphur and heavy oxygen in the remaining sulphate pool and a characteristic isotope fractionation pattern are a clear evidence for the activity of sulphate-reducing bacteria utilising the injected glycerol as an electron donor. This activity seemed to intensify over the observation period. The spatial distribution of sulphate reduction activity, however, appeared to be highly inhomogeneous. Rather than occurring ubiquitously, sulphate reduction activity seemed to concentrate in a defined reaction zone. Regardless of the inhomogeneous distribution, the overall turnover of sulphate during the period of investigation proves the applicability of this enhanced natural attenuation method to handle the restoration of aquifers contaminated with AMD. PMID- 22092250 TI - Trait means and desirabilities as artifactual and real sources of differential stability of personality traits. AB - Using data from 3 personality trait inventories and 7 samples, we show that trait items that have means near the scale midpoint and that vary more in their perceived desirability (e.g., items related to dominance, creativity, traditionalism, and organization) tend to be more stable over time, whereas items with means near the scale maximum or minimum and that vary less in their perceived desirability (e.g., items related to agreeableness, intellect, and reliability) tend to be less stable. Our findings indicate that items with means near the scale maximum or minimum have lower stabilities primarily due to having lower measurement dependability (i.e., short-term stabilities unlikely to reflect true change). However, items varying more in their desirability are more stable even after accounting for measurement dependability, consistent with the view that trait stability is facilitated in part by individuals actively working to develop in the direction they find desirable. PMID- 22092251 TI - Differences in clinical features and in-hospital outcomes of older adults with tako-tsubo cardiomyopathy. AB - OBJECTIVES: To describe the clinical characteristics and in-hospital outcomes of older adults with tako-tsubo cardiomyopathy (TTC). DESIGN: Partially retrospective, partially prospective observational study. SETTING: Eleven Italian referral cardiac centers included in the Tako-tsubo Italian Network. PARTICIPANTS: One hundred ninety consecutive individuals with TTC (92.1% female, mean age 66) were divided into three groups according to age (<65, n = 78; 65-74, n = 61; >=75, n = 51). MEASUREMENTS: Clinical findings and in-hospital outcomes were evaluated in each group. RESULTS: Participants aged 65 and older had a greater prevalence of hypertension (P = .001) and a lower glomerular filtration rate (P < .001), and those aged 65 to 74 had a greater prevalence of psychiatric disorders (P = .01), ST-segment elevation on admission (P = .01) and a cerebrovascular disease (P = .003) than those younger than 65. Despite similar left ventricular ejection fraction (LVEF) on admission (P = .26), the oldest group had a lower LVEF at discharge (P = .03). Inotropic agents were used more frequently in older adults (P = .03). In-hospital composite adverse events (all cause death, acute heart failure, life-threatening arrhythmias, stroke, and cardiogenic shock; P = .03) and overall complications (P = .004) were more common in participants aged 75 and older. Overall in-hospital mortality was low (2.8%) but was more prevalent in participants aged 75 and older (6.3%). On multivariate analysis, age of 75 and older (hazard ratio (HR) = 2.45, 95% confidence interval (CI) = 1.28-5.82, P = .04) and LVEF on admission (HR = 0.874, 95% CI = 0.81-0.95, P < .001) were the only independent predictors of in-hospital adverse events. CONCLUSION: The clinical profile of participants aged 75 and older with TTC was different from that of those younger than 75 with TTC, and they had a higher in hospital complication rate. PMID- 22092252 TI - Selective removal of undifferentiated human embryonic stem cells using magnetic activated cell sorting followed by a cytotoxic antibody. AB - One of the most pertinent concerns of using differentiated cells derived from human embryonic stem cells (hESC) is the presence of residual undifferentiated hESC, because they carry a risk of teratoma formation. A new cell-cell separation approach that eliminates teratoma-forming hESC in order to ensure safer cell therapy was developed. By combining antibodies (IgMs or IgGs) for the selective removal of undifferentiated hESC using magnetic activated cell sorting (MACS) followed by selective killing of residual hESC with the unique cytotoxic antibody mAb 84, the required purity of differentiated hESC can be achieved. The applicability and robustness of this separation strategy is shown here in a case study using pools of undifferentiated hESC and human fibroblast cells at different ratios (5%-50% hESC) to reflect the different scenario of contaminating hESC in a differentiated cell population. Notably, 97.2%-99.7% of the hESC were removed after the MACS step and 99.1%-100%, after the mAb 84 treatment step, which was confirmed by double-staining flow cytometry and RT-qPCR analysis. These in vitro findings were further validated in an in vivo severe combined immunodeficiency (SCID) mouse model. Importantly, we observed the absence of teratoma formation in eight out of nine SCID mice 28 weeks postinjection of cells after the MACS step, whereas teratomas were observed in all of the controls. Thus, the combination of MACS with the unique cytotoxic antibody mAb 84 constitutes an indispensible tool for successful and safe cell therapy. PMID- 22092253 TI - Foot strike patterns of recreational and sub-elite runners in a long-distance road race. AB - Although the biomechanical properties of the various types of running foot strike (rearfoot, midfoot, and forefoot) have been studied extensively in the laboratory, only a few studies have attempted to quantify the frequency of running foot strike variants among runners in competitive road races. We classified the left and right foot strike patterns of 936 distance runners, most of whom would be considered of recreational or sub-elite ability, at the 10 km point of a half-marathon/marathon road race. We classified 88.9% of runners at the 10 km point as rearfoot strikers, 3.4% as midfoot strikers, 1.8% as forefoot strikers, and 5.9% of runners exhibited discrete foot strike asymmetry. Rearfoot striking was more common among our sample of mostly recreational distance runners than has been previously reported for samples of faster runners. We also compared foot strike patterns of 286 individual marathon runners between the 10 km and 32 km race locations and observed increased frequency of rearfoot striking at 32 km. A large percentage of runners switched from midfoot and forefoot foot strikes at 10 km to rearfoot strikes at 32 km. The frequency of discrete foot strike asymmetry declined from the 10 km to the 32 km location. Among marathon runners, we found no significant relationship between foot strike patterns and race times. PMID- 22092254 TI - Quality of pharmacokinetic studies in critically ill patients receiving continuous renal replacement therapy. AB - Continuous renal replacement therapy (CRRT) is the preferred renal replacement therapy modality in the critically ill. We aimed to reveal the literature on the pharmacokinetic studies in critically ill patients receiving CRRT with special reference to quality assessment of these studies and the CRRT dose. We conducted a systematic review by searching the MEDLINE, EMBASE, and the Cochrane databases to December 2009 and bibliographies of relevant review articles. We included original studies reporting from critically ill adult subjects receiving CRRT because of acute kidney injury with a special emphasis on drug pharmacokinetics. We used the minimum reporting criteria for CRRT studies by Acute Dialysis Quality Initiative (ADQI) and, second, the Downs and Black checklist to assess the quality of the studies. We calculated the CRRT dose per study. We included pharmacokinetic parameters, residual renal function, and recommendations on drug dosing. Of 182 publications, 95 were considered relevant and 49 met the inclusion criteria. The median [interquartile range (IQR)] number of reported criteria by ADQI was 7.0 (5.0-8.0) of 12. The median (IQR) Downs and Black quality score was 15 (14-16) of 32. None of the publications reported CRRT dose directly. The median (IQR) weighted CRRT dose was 23.7 (18.8-27.9) ml/kg/h. More attention should be paid both to standardizing the CRRT dose and reporting of the CRRT parameters in pharmacokinetic studies. The general quality of the studies during CRRT in the critically ill was only moderate and would be greatly improved by reports in concordant with the ADQI recommendations. PMID- 22092255 TI - Raman doping profiles of polyelectrolyte SWNTs in solution. AB - We present a resonance Raman study of electrochemical charge transfer doping on polyelectrolyte single-walled carbon nanotubes (SWNTs) in solution. Changes in the intensity of the radial breathing modes of well-identified SWNTs are measured as a function of the electrochemical potential. The intensity is maximum when the nanotubes are neutral. Unexpectedly, the Raman signal decreases as soon as charges are transferred to the nanotubes, leading to intensity profiles that are triangular for metallic and trapezoidal for semiconducting nanotubes. A key result is that the width in energy of the plateaus for the semiconducting nanotubes is roughly equal to the optical gap (rather than the free carrier gap). While these experiments can be used to estimate the energy levels of individual nanotubes, strong dynamical screening appears to dominate in individual SWNT polyelectrolytes so that only screened energy levels are being probed. PMID- 22092256 TI - Biomechanical evaluation of screw-in femoral implant in cementless total hip system. AB - OBJECTIVE: To compare (1) proximal femoral axial strains, (2) femoral head deflection, and (3) failure mechanical properties, between Helica head and neck prosthesis implanted femora and normal femora. STUDY DESIGN: In vitro study. SAMPLE POPULATION: Cadaveric canine femora (n = 5 pair). METHODS: Femoral bone strains and head displacement during in vitro simulation of midstance of the gallop were evaluated using cadaveric femurs cyclically loaded in vitro. Strains and displacements were compared within femurs, before and after, prosthesis implantation; and throughout cycling to seek evidence of movement with cyclic loading. Subsequently, implanted femurs and contralateral, intact femurs were loaded to failure to compare failure mechanical properties and modes of failure. RESULTS: Proximal femoral axial strains were significantly different between intact and implanted femora on all 4 cortical surfaces (P < .05). Compressive strains were lower in the implanted femur on all cortical surfaces, except on the caudal surface which was higher. No difference was noted for femoral head angle under an axial load corresponding to gallop (P > .05). Vertical head displacement was ~0.1 mm greater for implanted femora than intact femora (P < .05). Yield and failure loads and yield energy of implanted femora were 39-54% lower than those for intact femora (P < .05). Mode of failure for both the intact and implanted femora did not appear to be different. CONCLUSION: Helica femoral prosthesis alters strain distribution in the proximal aspect of the femur and exhibits initial micromotion. Failure load in axial compression of the Helica-implanted femur is less than that of the normal femur, but greater than that expected in vivo. PMID- 22092257 TI - A once-per-day, drug-in-food protocol for prolonged administration of antiepileptic drugs in animal models. AB - PURPOSE: Convenient and effective methods for administering potential antiepileptic drugs (AEDs) chronically should facilitate many experiments in animal models of chronic epilepsy with spontaneous recurrent seizures. This proof of-principle study aimed to optimize a once-per-day, drug-in-food protocol by testing the effect of carbamazepine (CBZ) on the frequency of convulsive seizures in rats with kainate-induced epilepsy. METHODS: Adult male rats were given repeated low-dose kainate injections until convulsive status epilepticus persisted for >3 h. After the rats developed spontaneous recurrent seizures, food pellets with CBZ (30, 100, or 300 mg/kg/day) were provided once per day in three 2-week trials (n = 7-9 rats) involving 5 days of CBZ or control treatment, separated by two recovery days within a trial. The total amount of food provided and consumed per day corresponded to a normal caloric diet (60 g/kg/day). KEY FINDINGS: When provided once per day, all animals ate the CBZ-containing food irregularly but continuously throughout the 24-h day. With this daily feeding protocol, CBZ significantly reduced the frequency of spontaneous convulsive seizures in a dose-dependent manner. It is important to note that the effect of CBZ was consistent across the 5 days and throughout each day of the trials. With food administered at 9:00 a.m., and blood assayed at 5:00 p.m., higher food levels of CBZ resulted in higher plasma concentrations of CBZ. SIGNIFICANCE: This AED-in-food protocol is simple, efficient, inexpensive, reliable, and noninvasive; it allows easier long-term drug administration and is less stressful and more humane than other methods of AED administration. PMID- 22092258 TI - Depression is associated with sarcopenia, not central obesity, in elderly korean men. AB - OBJECTIVES: To examine the relationship between depression and various components of body composition, including fat and muscle, in elderly Koreans. DESIGN: A cross-sectional sample of a longitudinal cohort from the Ansan Geriatric (AGE) Study. SETTING: Elderly people living in urban area (Ansan City, South Korea). PARTICIPANTS: Eight hundred thirty-six participants (378 male, 458 female) aged 60 and older were recruited from April 2006 to January 2008. MEASUREMENTS: Depressive symptoms were examined using the Korean version of the 30-item Geriatric Depression Scale (KGDS). Participants taking antidepressant medications or with a KGDS score of 14 or greater were classified as having depression. Abdominal visceral fat area (VFA) and subcutaneous fat area were assessed using single-slice computed tomography, and appendicular skeletal muscle mass (ASM) and percentage body fat (%BF) were determined using whole-body dual-energy X-ray absorptiometry. RESULTS: Elderly men with depression had a lower ASM than those without depression (P = .01) after adjusting for age, body weight, and height. In men, the risk of depression was lower with higher body mass index (BMI) (odds ratio (OR) per 1-standard deviation (SD) increase = 0.70, 95% confidence interval (CI) = 0.51-0.96) after adjusting for all confounding variables and higher ASM (OR per 1-SD increase = 0.49; 95% CI = 0.29-0.85) after controlling for age, height, and weight. Similarly, depression was negatively associated with BMI in women (OR per 1-SD increase = 0.73; 95% CI = 0.56-0.95). Waist circumference, %BF, and VFA were not consistently associated with depression in men or women. CONCLUSION: Depression in elderly Koreans is associated with low body mass and sarcopenia, especially in men. PMID- 22092259 TI - Physician social networks and variation in prostate cancer treatment in three cities. AB - OBJECTIVE: To examine whether physician social networks are associated with variation in treatment for men with localized prostate cancer. DATA SOURCE: 2004 2005 Surveillance, Epidemiology and End Results-Medicare data from three cities. STUDY DESIGN: We identified the physicians who care for patients with prostate cancer and created physician networks for each city based on shared patients. Subgroups of urologists were defined as physicians with dense connections with one another via shared patients. PRINCIPAL FINDINGS: Subgroups varied widely in their unadjusted rates of prostatectomy and the racial/ethnic and socioeconomic composition of their patients. There was an association between urologist subgroup and receipt of prostatectomy. In city A, four subgroups had significantly lower odds of prostatectomy compared with the subgroup with the highest rates of prostatectomy after adjusting for patient clinical and sociodemographic characteristics. Similarly, in cities B and C, subgroups had significantly lower odds of prostatectomy compared with the baseline. CONCLUSIONS: Using claims data to identify physician networks may provide an insight into the observed variation in treatment patterns for men with prostate cancer. PMID- 22092260 TI - Characteristics and kinetics of phosphate adsorption on dewatered ferric-alum residuals. AB - The characteristics and kinetics of phosphate (P) adsorption on dewatered ferric alum water treatment residuals (Fe-Al-WTRs) have been investigated. The existence of both aluminum (Al) and iron (Fe) in the residuals can result in significantly high P adsorption capacities. The P adsorption kinetics of Fe-Al-WTRs exhibited an initial rapid phase, followed by a slower phase. This could be described by three models, including a pseudo-first-order equation, a pseudo-second-order equation, and a double-constant rate equation. The latter was especially good for those runs with initial P concentrations of 500 and 1000 mg L(-1). Both the Langmuir and Freundlich isotherms fit the experimental data well, particularly the Freundlich isotherm, which had a correlation coefficient of 0.9930. The maximum measured P adsorption capacity of Fe-Al-WTRs was 45.42 mg g(-1), which is high when compared to those of most WTRs, as well as other reported adsorbents. The results also show that the P adsorption is a spontaneous endothermic process. Highest P adsorption capacities of Fe-Al-WTRs were measured at low pHs and a particle size range of 0.6 to 0.9 mm. PMID- 22092261 TI - Robust identification of binding hot spots using continuum electrostatics: application to hen egg-white lysozyme. AB - Binding hot spots, protein regions with high binding affinity, can be identified by using X-ray crystallography or NMR spectroscopy to screen libraries of small organic molecules that tend to cluster at such hot spots. FTMap, a direct computational analogue of the experimental screening approaches, uses 16 different probe molecules for global sampling of the surface of a target protein on a dense grid and evaluates the energy of interaction using an empirical energy function that includes a continuum electrostatic term. Energy evaluation is based on the fast Fourier transform correlation approach, which allows for the sampling of billions of probe positions. The grid sampling is followed by off-grid minimization that uses a more detailed energy expression with a continuum electrostatics term. FTMap identifies the hot spots as consensus clusters formed by overlapping clusters of several probes. The hot spots are ranked on the basis of the number of probe clusters, which predicts their binding propensity. We applied FTMap to nine structures of hen egg-white lysozyme (HEWL), whose hot spots have been extensively studied by both experimental and computational methods. FTMap found the primary hot spot in site C of all nine structures, in spite of conformational differences. In addition, secondary hot spots in sites B and D that are known to be important for the binding of polysaccharide substrates were found. The predicted probe-protein interactions agree well with those seen in the complexes of HEWL with various ligands and also agree with an NMR-based study of HEWL in aqueous solutions of eight organic solvents. We argue that FTMap provides more complete information on the HEWL binding site than previous computational methods and yields fewer false-positive binding locations than the X-ray structures of HEWL from crystals soaked in organic solvents. PMID- 22092262 TI - Studies on the inactivation of selected viral and bacterial fish pathogens at high pH for waste disposal purposes. AB - This study investigated the use of alkaline hydrolysis at ambient temperature for inactivation of selected fish pathogens in fish tissues under conditions approximating those that are likely to be found in the aquaculture industry. Infectious salmon anaemia virus (ISAV) and Lactococcus garvieae have been determined in a previous study to be the most resistant virus and bacteria to pH 12 from a wide range of viruses and bacteria tested. They were spiked at high titres into fish extracts that were then treated with 1 m sodium hydroxide (NaOH). Viable L. garvieae was not detected in the treated fish extract after 1 h, and ISAV was not detected after 24-h exposure. Field mortalities of Atlantic salmon, Salmo salar L., caused by infectious pancreatic necrosis virus were treated by alkaline hydrolysis at ambient temperature. The macerated fish mortalities contained a high titre of virus (3.38 * 108 TCID50 g-1) that was reduced to approximately 2.2 * 103 TCID50 g-1 after 24-h exposure to NaOH, and virus was not detected after exposure for 48 h. The results suggest that alkaline hydrolysis at ambient temperature has potential as a biosecure treatment method for fish by-products containing fish pathogens. PMID- 22092263 TI - Functional connectivity and infant spatial working memory: a frequency band analysis. AB - The limited research on the functional meaning of infant EEG frequency bands has used measures of EEG power. The purpose of this study was to examine task-related changes in frontal EEG coherence measures for three infant EEG frequency bands (2 5 Hz, 6-9 Hz, 10-13 Hz) during a spatial working memory task. Eight-month-olds exhibited baseline-to-task changes in frontal EEG coherence for all infant frequency bands. Both the 2-5 Hz and the 10-13 Hz bands differentiated frontal functional connectivity during the distinct processing stages, but each band provided unique information. The 10-13 Hz band, however, was the only frequency band to distinguish frontal EEG coherence values during correct and incorrect responses. These data reveal valuable information concerning frontal functional connectivity and the functional meaning of three different infant EEG frequency bands during working memory processing. PMID- 22092265 TI - Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. AB - Until recently, microbial identification in clinical diagnostic laboratories has mainly relied on conventional phenotypic and gene sequencing identification techniques. The development of matrix-assisted laser desorption ionization time of-flight mass spectrometry (MALDI-TOF MS) devices has revolutionized the routine identification of microorganisms in clinical microbiology laboratories by introducing an easy, rapid, high throughput, low-cost, and efficient identification technique. This technology has been adapted to the constraint of clinical diagnostic laboratories and has the potential to replace and/or complement conventional identification techniques for both bacterial and fungal strains. Using standardized procedures, the resolution of MALDI-TOF MS allows accurate identification at the species level of most Gram-positive and Gram negative bacterial strains with the exception of a few difficult strains that require more attention and further development of the method. Similarly, the routine identification by MALDI-TOF MS of yeast isolates is reliable and much quicker than conventional techniques. Recent studies have shown that MALDI-TOF MS has also the potential to accurately identify filamentous fungi and dermatophytes, providing that specific standardized procedures are established for these microorganisms. Moreover, MALDI-TOF MS has been used successfully for microbial typing and identification at the subspecies level, demonstrating that this technology is a potential efficient tool for epidemiological studies and for taxonomical classification. PMID- 22092264 TI - Delay in seeing a doctor due to cost: disparity between older adults with and without disabilities in the United States. AB - OBJECTIVE: To examine the disparity in delaying seeing a doctor due to cost between older adults with and without disabilities, and whether the disparity could be explained by health and financial variables. DATA SOURCES: Nationally representative sample of community-dwelling adults aged >=65 who have health insurance and a usual source of care from the 2006 Behavioral Risk Factor Surveillance System (n = 85,015). STUDY DESIGN: This cross-sectional study used sequential logistic regression models to examine the associations of delaying seeing a doctor due to cost with disability status, including demographic, health, and financial variables. PRINCIPAL FINDINGS: Older adults with disabilities had significantly higher odds of delaying seeing a doctor due to cost compared to older adults without disabilities after controlling for demographic, health, and financial factors. Although health and financial variables collectively attenuated the disparity, they did not fully explain the disparity. CONCLUSIONS: Despite having health insurance and a usual source of care, older adults with disabilities encountered greater economic difficulties in seeing a doctor than their counterparts without disabilities. Policy makers should continue addressing the economic burden to improve timely visits to health care providers. PMID- 22092266 TI - Multiple markers pyrosequencing reveals highly diverse and host-specific fungal communities on the mangrove trees Avicennia marina and Rhizophora stylosa. AB - Fungi are important actors in ecological processes and trophic webs in mangroves. Although saprophytic fungi occurring in the intertidal part of mangrove have been well studied, little is known about the diversity and structure of the fungal communities in this ecosystem or about the importance of functional groups like pathogens and mutualists. Using tag-encoded 454 pyrosequencing of the ITS1, ITS2, nu-ssu-V5 and nu-ssu-V7 regions, we studied and compared the fungal communities found on the marine and aerial parts of Avicennia marina and Rhizophora stylosa trees in a mangrove in New Caledonia. A total of 209,544 reads were analysed, corresponding to several thousand molecular operational taxonomic units (OTU). There is a marked zonation in the species distribution, with most of the OTU being found specifically in one of the microhabitat studied. Ascomycetes are the dominant phylum (82%), Basidiomycetes are very rare (3%), and 15% of the sequences correspond to unknown taxa. Our results indicate that host specificity is a key factor in the distribution of the highly diverse fungal communities, in both the aerial and intertidal parts of the trees. This study also validates the usefulness of multiple markers in tag-encoded pyrosequencing to consolidate and refine the assessment of the taxonomic diversity. PMID- 22092267 TI - Neuromuscular blocking agents for electroconvulsive therapy: a systematic review. AB - Electroconvulsive therapy (ECT) is the transcutaneous application of small electrical stimuli to the brain to induce generalised seizures for the treatment of selected psychiatric disorders. The clinical indications for ECT as an effective therapeutic modality have been considerably expanded since its introduction. Anaesthesia and neuromuscular blocking agents (NMBAs) are required to ensure patients' safety during ECT. The optimal dose of muscle relaxant for ECT reduces muscle contractions without inducing complete paralysis. Slight residual motor convulsive activity is helpful in ascertaining that a seizure has occurred, while total paralysis prolongs the procedure unnecessarily. Suxamethonium is commonly used, but nondepolarising NMBAs are indicated in patients with certain comorbidities. In this review, we summarise current concepts of NMBA management for ECT. PMID- 22092268 TI - Hybrid field-assisted solid-liquid-solid dispersive extraction for the determination of organochlorine pesticides in tobacco with gas chromatography. AB - A novel one-step sample preparation technique termed hybrid field-assisted solid liquid-solid dispersive extraction (HF-SLSDE) was developed in this study. A simple glass system equipped with a condenser was designed as an extraction vessel. The HF-SLSDE technique was a three-phase dispersive extraction approach. Target analytes were extracted from the sample into the extraction solvent enhanced by the hybrid field. Meanwhile, the interfering components were adsorbed by dispersing sorbent. No cleanup step preceded chromatographic analysis. The efficiency of the HF-SLSDE approach was demonstrated in the determination of organochlorine pesticide (OCP) residues in tobacco with a gas chromatography electron capture detector (GC-ECD). Various operation conditions were studied systematically. Low detection limits (0.3-1.6 MUg/kg) and low quantification limits (1.0-4.5 MUg/kg) were achieved under the optimized conditions. The recoveries of OCPs ranged from 70.2% to 118.2%, with relative standard deviations of <9.6%, except for the lowest fortification level. Because of the effect of the hybrid field, HF-SLSDE showed significant predominance compared with other extraction techniques. The dispersing sorbent with good cleanup ability used in this study was also found to be a microwave absorption medium, which could heat the nonpolar extraction solvent under microwave irradiation. Different microstructures of tobacco samples before and after extractions demonstrated the mechanism of HF-SLSDE was based on an explosion at the cell level. According to the results, HF-SLSDE was proved to be a simple and effective sample preparation method for the analysis of pesticide residues in solid samples and could potentially be extended to other nonpolar target analytes in a complex matrix. PMID- 22092270 TI - Acceptability of the H1N1 vaccine among older adults: the interplay of message framing and perceived vaccine safety and efficacy. AB - This study examines the relative effectiveness of using gain- versus loss-framed messages to promote H1N1 vaccination among older adults, focusing on the moderating roles of perceived vaccine safety and efficacy. An experiment was conducted with older adults recruited from senior centers in the state of Maryland. Results show that older adults who perceived low vaccine efficacy developed greater intentions to receive the vaccine when presented with a loss framed message (versus a gain-framed message). For those who perceived high vaccine efficacy, message framing did not make a difference in postexposure intentions. Evidence regarding the interaction between message framing and perceived vaccine safety is limited. Theoretical and practical implications of the findings are discussed. PMID- 22092269 TI - Using fuzzy set qualitative comparative analysis (fs/QCA) to explore the relationship between medical "homeness" and quality. AB - OBJECTIVE: Determine, using fuzzy set qualitative comparative analysis (fs/QCA), the relationship between patient-centered medical home (PCMH) systems and quality in 21 NCQA recognized medical homes. DATA SOURCES/STUDY SETTING: Primary data collected in 2009, including measures of optimal diabetes care (ODC), preventive services up-to-date (PSUTD), patient experience (PEX), survey data assessing PCMH capabilities (PPC-RS), and other clinic characteristics. STUDY DESIGN: Cross sectional study identifying associations between PPC-RS domains, demographic, socioeconomic, and co-morbidity measures, and quality outcomes. DATA COLLECTION/EXTRACTION METHODS: PPC-RS scores were obtained by surveying clinic leaders. PSUTD and ODC scores were obtained from provider performance data. PEX data were obtained from patient surveys. Demographic, socioeconomic, and co morbidity data were obtained from EMR and census data. PRINCIPAL FINDINGS: fs/QCA identified associations between all three outcomes and PCMH capabilities: ODC and team-based care; PSUTD and preventive services systems; and all three outcomes and provider performance reporting systems. Previous statistical analysis of this data had failed to identify these relationships. CONCLUSIONS: fs/QCA identified important associations that were overlooked using conventional statistics in a small-N health services data set. PCMH capabilities are associated with quality outcomes. PMID- 22092271 TI - The moderating effect of physical activity on cardiovascular reactivity following single fat feedings. AB - This experiment examined the effects of consuming a high-fat meal on cardiovascular reactivity and the ability of exercise to act as a moderator between dietary fat consumption and cardiovascular reactivity. Forty healthy, college-age students were randomly assigned to one of four experimental groups: (1) low-fat meal, no exercise; (2) low-fat meal, postprandial exercise; (3) high fat meal, no exercise; and (4) high-fat meal, postprandial exercise. To induce stress, all participants performed a public speaking task, while heart rate and blood pressure reactivity were measured. Multilevel analyses revealed that consuming a high-fat meal led to heightened mean arterial pressure reactivity. Acute high-intensity exercise resulted in attenuated heart rate and mean arterial pressure reactivity. The results of this study offer insight into how diet and exercise may influence cardiovascular reactivity, which is a key determinant of cardiovascular disease. PMID- 22092272 TI - Protective effect of Rubia cordifolia on reserpine-induced orofacial dyskinesia. AB - In this study, the neuroprotective potential and in vivo antioxidant status of extract of roots and rhizomes of Rubia cordifolia L (MERC) in reserpine-induced orofacial dyskinesia was studied. Reserpine (1 mg/kg, s.c.) on day 1, 3 and 5 was used to induce orofacial dyskinesia. At the end of treatment schedule, MERC significantly inhibited reserpine-induced vacuous chewing movements, tongue protrusions, orofacial bursts, catalepsy. MERC significantly increased locomotion and rearing in open field test. MERC exhibited significant elevation in the levels of superoxide dismutase, catalase, glutathione reductase and inhibition of lipid peroxidation in forebrain region, compared with the reserpine treated group. It significantly elevated dopamine levels in the forebrain region. GCMS revealed the presence of anthraquinones, having strong antioxidant activity. It is concluded that oxidative stress might play an important role in reserpine induced abnormal oral movements and MERC significantly protected animals against reserpine-induced orofacial dyskinesia and has great potential in treatment of neuroleptic induced orofacial dyskinesia. PMID- 22092273 TI - T-RFLP analysis of bacterial communities in the midguts of Apis mellifera and Apis cerana honey bees in Thailand. AB - This study investigated bacterial community structures in the midguts of Apis mellifera and Apis cerana in Thailand to understand how bacterial communities develop in Apis species. The bacterial species present in replicate colonies from different locations and life stages were analysed. PCR amplification of bacterial 16S rRNA gene fragments and terminal restriction fragment length polymorphism analyses revealed a total of 16 distinct terminal restriction fragments (T-RFs), 12 of which were shared between A. mellifera and A. cerana populations. The T-RFs were affiliated to Beta- and Gammaproteobacteria, Firmicutes and Actinomycetes. The Gammaproteobacteria were found to be common in all stages of honey bee, but in addition, the Firmicutes group was found to be present in the worker bees. Bacterial community structure showed no difference amongst the replicate colonies, but was affected to some degree by geographical location, life stage and species of honey bees. PMID- 22092274 TI - The role of perfectionism in daily self-esteem, attachment, and negative affect. AB - This study of university students (64 men, 99 women) examined the role of self critical (SC) and personal standards (PS) higher order dimensions of perfectionism in daily self-esteem, attachment, and negative affect. Participants completed questionnaires at the end of the day for 7 consecutive days. Trait and situational influences were found in the daily reports of self-esteem, attachment, and affect. In contrast to PS perfectionism, SC perfectionism was strongly related to aggregated daily reports of low self-esteem, attachment fears (fear of closeness, fear of dependency, fear of loss), and negative affect as well as instability indexes of daily self-esteem, attachment, and negative affect. Multilevel modeling indicated that both SC and PS perfectionists were emotionally reactive to decreases in self-esteem, whereas only SC perfectionists were emotionally reactive to increases in fear of closeness with others. These results demonstrate the dispositional and moderating influences of perfectionism dimensions on daily self-esteem, attachment, and negative affect. PMID- 22092275 TI - Processing of equine bone marrow using the automated MarrowXpress System: RBC depletion, volume reduction, and mononuclear cell recovery. AB - BACKGROUND: The therapeutic use of bone marrow-derived mononuclear cells (MNCs) and mesenchymal stem cells for the treatment of soft tissue and orthopedic injuries in equine patients is expanding. After collection, bone marrow must be reduced in volume and depleted of RBCs for immediate therapeutic use or to prepare cells for culture or cryopreservation and storage. The MarrowXpress (MXP) System is an automated, closed, sterile system designed to process human bone marrow samples. OBJECTIVES: The purpose of this study was to evaluate the capacity of the MXP System to process equine bone marrow to reduce volume, deplete RBCs, and enhance recovery of MNCs. METHODS: Bone marrow was collected from 47 horses into 2 60-mL syringes containing heparin and processed using the MXP System. HCT, total nucleated cell (TNC) count, and MNC count were obtained for each sample before and after processing using an Advia 120 hematology analyzer. Volume reduction, RBC depletion, and recovery of TNCs and MNCs were calculated. RESULTS: For equine bone marrow samples, mean values were 73.2% for RBC depletion and 78.0% for volume reduction. TNC count before processing was 2.5 +/- 1.2 * 10(7) and after processing was significantly higher at 7.8 +/- 3.3 * 10(7) (P < .0001), with a recovery of 68.5 +/- 24.5% (mean +/- SD). MNC count before processing was 1.1 +/- 0.9 * 10(7) and after processing was significantly higher at 3.8 +/- 1.9 * 10(7) (P < .0001), with a recovery 73.0 +/- 31.5%. CONCLUSIONS: The MXP System can reliably reduce volume and deplete RBCs from aspirates of equine bone marrow aspirates. MNCs can be recovered in a reproducible and sterile manner. Further studies evaluating the effects of the MXP System on cell viability, identification of mesenchymal stem cells (MSCs), and the efficacy of MSC expansion are warranted. PMID- 22092276 TI - Relationships between physiological, anthropometric, and skill qualities and playing performance in professional rugby league players. AB - In this study, we investigated the relationship between physiological, anthropometric, and skill qualities and playing performance in professional rugby league players. Fifty-eight high-performance rugby league players underwent measurements for anthropometry (height, body mass, sum of seven skinfolds), physiological (speed, change of direction speed, lower body muscular power, repeated-sprint ability, prolonged high-intensity intermittent running ability, and estimated maximal aerobic power), technical skill (tackling proficiency, draw and pass proficiency), and perceptual skill (reactive agility, pattern recall, pattern prediction) qualities. National Rugby League matches were coded for attacking (e.g. line breaks, try assists, etc.) and defensive (e.g. missed tackles, tackling efficiency, etc.) statistics commonly used to assess rugby league playing performance. The number of line break assists was significantly associated (P < 0.05) with greater playing experience (r = 0.36), dual-task draw and pass proficiency (r = 0.54), reactive agility (r = 0.29), and pattern recall (r = 0.32) and prediction (r = 0.28) ability, while faster speed over 40 m (r = 0.42) was associated (P < 0.05) with a higher number of tries scored. Greater age and playing experience, better lower body muscular power, and faster 10 m and 40 m speed were significantly associated (P < 0.05) with the number of tackle attempts (positive), tackles completed (positive), and proportion of missed tackles (negative). These findings demonstrate that well-developed physical and skill qualities are associated with effective playing performance in National Rugby League players. PMID- 22092277 TI - Scutellarin inhibits translocation of protein kinase C in diabetic thoracic aorta of the rat. AB - The aims of the present study were to explore the effects of: (i) scutellarin (Scu) on protein kinase C (PKC) translocation caused by diabetic conditions in diabetic rat thoracic aorta; and (ii) phorbol-12-myristate-13-acetate (PMA) treatment of cultured thoracic aortic smooth muscle cells. Diabetes was induced in rats by streptozotocin and diabetic rats were divided into two groups: (i) an Scu-treated group, administered 0.1 g/kg Scu by gavage; and (ii) an aminoquanidine (AG)-treated group, which received dietary supplementation of 0.1% AG from Week 1 of diabetes induction. After 10 weeks, rats were killed and thoracic aortic smooth muscle cells were isolated and cultured. Cell fractions were obtained by ultracentrifugation and PKC activity was assayed by ELISA, whereas the distribution of PKC was verified by western immunoblotting. The PKC activity in the membrane fraction of thoracic aortic smooth muscle cells was significantly increased in diabetic compared with control rats, whereas the administration of Scu significantly inhibited this increase. Phorbol myristate acetate (100 nmol/L, 10 min) induced the translocation of the PKCalpha, betaI, betaII, delta and epsilon isoforms, whereas 48 h pretreatment of cells with 1 MUmol/L Scu significantly inhibited PMA-induced PKCbetaI, betaII and delta translocation. The results of the present study suggest that Scu inhibits the translocation of PKC in vivo and in vitro and may have value as a drug in the treatment of diabetic complications via its inhibition of PKC betaI, betaII and delta translocation. PMID- 22092278 TI - The severity of sevoflurane-induced malignant hyperthermia. AB - BACKGROUND: Malignant hyperthermia (MH) is a potentially fatal complication of general anesthesia triggered by volatile anesthetics. In animal studies, sevoflurane has been reported to be a weak triggering agent. The aim of this study was to evaluate the clinical severity of sevoflurane-induced MH compared to isoflurane. METHODS: From the Japanese MH database containing information for 520 MH cases since 1961, we analyzed 147 cases classified by the MH Clinical Grading Scale (CGS) as 'very likely' or 'almost certain', accumulated from 1990 to 2009. Sevoflurane without succinylcholine (S-SCh (-) group) was given to 48 cases, and isoflurane without succinylcholine (I-SCh (-) group) was given to 30. Variables studied were outcome, CGS score, CGS rank, the first MH sign, and time from induction to onset of MH (occurrence time). Clinical signs and maximum laboratory data from six processes of the CGS were also analyzed. Each of the Mann-Whitney U test or the unpaired t-test was used for group comparisons. RESULTS: Mortality was 8.3% in the S-SCh (-) group and 10.0% in the I-SCh (-) group (P = 0.803). The CGS scores were 53.4 (SD, 12.2) and 52.3 (11.7) (P = 0.691), respectively. The five processes of the CGS did not differ between groups. Median occurrence times were 72.5 minutes (range, 36.3-127.5) and 65.0 minutes (30.0-131.3), respectively (P = 0.890). CONCLUSION: There were no clinically apparent differences between MH triggered by sevoflurane and isoflurane, and thus no evidence to support the postulate that sevoflurane is a weak or weaker MH triggering agent. PMID- 22092279 TI - A microfabricated platform to measure and manipulate the mechanics of engineered cardiac microtissues. AB - Engineered myocardial tissues can be used to elucidate fundamental features of myocardial biology, develop organotypic in vitro model systems, and as engineered tissue constructs for replacing damaged heart tissue in vivo. However, a key limitation is an inability to test the wide range of parameters (cell source, mechanical, soluble and electrical stimuli) that might impact the engineered tissue in a high-throughput manner and in an environment that mimics native heart tissue. Here we used microelectromechanical systems technology to generate arrays of cardiac microtissues (CMTs) embedded within three-dimensional micropatterned matrices. Microcantilevers simultaneously constrain CMT contraction and report forces generated by the CMTs in real time. We demonstrate the ability to routinely produce ~200 CMTs per million cardiac cells (<1 neonatal rat heart) whose spontaneous contraction frequency, duration, and forces can be tracked. Independently varying the mechanical stiffness of the cantilevers and collagen matrix revealed that both the dynamic force of cardiac contraction as well as the basal static tension within the CMT increased with boundary or matrix rigidity. Cell alignment is, however, reduced within a stiff collagen matrix; therefore, despite producing higher force, CMTs constructed from higher density collagen have a lower cross-sectional stress than those constructed from lower density collagen. We also study the effect of electrical stimulation on cell alignment and force generation within CMTs and we show that the combination of electrical stimulation and auxotonic load strongly improves both the structure and the function of the CMTs. Finally, we demonstrate the suitability of our technique for high-throughput monitoring of drug-induced changes in spontaneous frequency or contractility in CMTs as well as high-speed imaging of calcium dynamics using fluorescent dyes. Together, these results highlight the potential for this approach to quantitatively demonstrate the impact of physical parameters on the maturation, structure, and function of cardiac tissue and open the possibility to use high-throughput, low volume screening for studies on engineered myocardium. PMID- 22092280 TI - Prevalence of food avoidance and food allergy in Chinese patients with chronic urticaria. AB - BACKGROUND: Food avoidance is common among Chinese patients with chronic urticaria because food allergy is considered to be the cause of disease. The benefit of food avoidance and its relationship with food allergy is unknown. OBJECTIVES: The aims of this study were to examine the prevalence and effect of food avoidance and food allergy in patients with chronic urticaria. METHODS: Four hundred and ninety-four patients with chronic urticaria, who attended Peking University Third Hospital from January 2009 to December 2010, were studied. Food avoidance and its effect were investigated with a detailed questionnaire. Food allergy was diagnosed by serum food-specific immunoglobulin E (IgE), elimination diet based on food-specific IgE, and open food challenge. RESULTS: One hundred and fifty-eight patients (32%) avoided fish, shrimp, crab, lamb or beef prior to evaluation and 82.9% of them reported food avoidance ineffective. Out of 341 patients tested for serum food-specific IgE, 75 (22%) were positive, with soy, peanut, beef, lamb, chicken, crab and shrimp as the leading allergens. Chronic urticaria induced by food allergy was found in only 2.8% of patients. CONCLUSIONS: The prevalence of food avoidance is high and mostly ineffective in Chinese patients with chronic urticaria. Foods avoided do not correspond to serum food-specific IgE. The incidence of IgE-mediated urticaria, as demonstrated by open food challenge, is low. Physicians and patients should be aware of unnecessary dietary avoidance while seeking treatment of chronic urticaria. PMID- 22092281 TI - Characterization of the tandem-arrayed hiC6 genes in Antarctic and temperate strains of Chlorella vulgaris. AB - HIC6 is a group-3 late embryogenesis abundant protein found in Chlorella vulgaris. In the Antarctic strain NJ-7 of this unicellular green alga, it is encoded by a tandem array of five hiC6 genes (designated as NJ7hiC6-1, -2, -3, -4 and -5); in the temperate strain UTEX259, it is encoded by four hiC6 genes in tandem (designated as 259hiC6-1, -2, -3 and -4). Except for NJ7hiC6-3 and -4, the encoding regions of all other hiC6 genes differ from each other by 2-19 bp in each strain. Based on RT-PCR and sequencing of total hiC6 cDNA clones, the relative transcript abundance of each hiC6 gene was evaluated. NJ7hiC6-2 and 259hiC6-2 were not expressed or expressed at low levels, whereas 259hiC6-1 and NJ7hiC6-3/4 exhibited the highest hiC6 transcript levels in the respective strains. In vitro assays showed that different isoforms of HIC6 provided almost identical cryoprotection of lactate dehydrogenase. Our studies suggest that the formation of the tandem arrays of hiC6 in Chlorella is a process of gene duplications accompanied by gene expression divergence. PMID- 22092283 TI - Analysis of microRNA-size, small RNAs in Streptococcus mutans by deep sequencing. AB - MicroRNAs (miRNAs) are important modulators of gene expression in eukaryotic cells. However RNAs of the same size in bacteria have not been specifically discussed previously. Here, we provide a library of miRNA-size RNAs (msRNAs), which were registered by deep sequencing in Streptococcus mutans. Bioinformatic analysis of the whole set revealed more than 900 individual msRNA species. The cellular content of selected msRNAs was verified by quantitative RT-PCR and Northern blotting. The high abundance and discrete size of the subset of registered msRNAs suggest their functional significance, although the precise biological role of the RNA species revealed in S. mutans, which is one of the principle causative agents of dental caries, has to be elucidated. PMID- 22092282 TI - Is there a critical period for mossy fiber sprouting in a mouse model of temporal lobe epilepsy? AB - PURPOSE: Dentate granule cell axon (mossy fiber) sprouting creates an aberrant positive-feedback circuit that might be epileptogenic. Presumably, mossy fiber sprouting is initiated by molecular signals, but it is unclear whether they are expressed transiently or persistently. If transient, there might be a critical period when short preventative treatments could permanently block mossy fiber sprouting. Alternatively, if signals persist, continuous treatment would be necessary. The present study tested whether temporary treatment with rapamycin has long-term effects on mossy fiber sprouting. METHODS: Mice were treated daily with 1.5 mg/kg rapamycin or vehicle (i.p.) beginning 24 h after pilocarpine induced status epilepticus. Mice were perfused for anatomic evaluation immediately after 2 months of treatment ("0 delay") or after an additional 6 months without treatment ("6-month delay"). One series of sections was Timm stained, and an adjacent series was Nissl-stained. Stereologic methods were used to measure the volume of the granule cell layer plus molecular layer and the Timm positive fraction. Numbers of Nissl-stained hilar neurons were estimated using the optical fractionator method. KEY FINDINGS: At 0 delay, rapamycin-treated mice had significantly less black Timm staining in the granule cell layer plus molecular layer than vehicle-treated animals. However, by 6-month delay, Timm staining had increased significantly in mice that had been treated with rapamycin. Percentages of the granule cell layer plus molecular layer that were Timm-positive were high and similar in 0 delay vehicle-treated, 6-month delay vehicle-treated, and 6-month delay rapamycin-treated mice. Extent of hilar neuron loss was similar among all groups that experienced status epilepticus and, therefore, was not a confounding factor. Compared to naive controls, average volume of the granule cell layer plus molecular layer was larger in 0 delay vehicle-treated mice. The hypertrophy was partially suppressed in 0 delay rapamycin-treated mice. However, 6-month delay vehicle- and 6-month delay rapamycin-treated animals had similar average volumes of the granule cell layer plus molecular layer that were significantly larger than those of all other groups. SIGNIFICANCE: Status epilepticus-induced mossy fiber sprouting and dentate gyrus hypertrophy were suppressed by systemic treatment with rapamycin but resumed after treatment ceased. These findings suggest that molecular signals that drive mossy fiber sprouting and dentate gyrus hypertrophy might persist for >2 months after status epilepticus in mice. Therefore, prolonged or continuous treatment might be required to permanently suppress mossy fiber sprouting. PMID- 22092285 TI - Neglect - a consequence of austerity? PMID- 22092284 TI - Postpartum obsessive-compulsive disorder. AB - OBJECTIVE: To synthesize the extant literature on the prevalence, phenomenology, etiology and treatment of postpartum obsessive-compulsive disorder (OCD). A discussion of differential diagnosis between postpartum OCD and other postpartum psychiatric conditions (e.g., depression, psychosis) and nonpostpartum-onset OCD is provided. DATA SOURCES, STUDY SELECTION AND DATA EXTRACTION: All studies addressing postpartum OCD between the years 1950 and 2011 were reviewed. Data from all pertinent studies was explored as it related to postpartum OCD. DATA SYNTHESIS: Studies were organized based on their empirical technique (e.g., retrospective, prospective), population studied (e.g., clinical OCD, nonclinical populations, males), and etiological or treatment theory (e.g., cognitive behavioral). CONCLUSION: The prevalence, phenomenology, etiology, and treatment of postpartum OCD are reviewed. The limited data on treatment approaches and outcomes for postpartum OCD are highlighted with a discussion of the role of nurses in the prevention and identification of postpartum OCD. PMID- 22092286 TI - An oral health care guideline for institutionalised older people. AB - Institutionalized older people are prone to oral health problems and their negative impact due to frailty, disabilities, multi-morbidity, and multiple medication use. Until recently, no evidence-based oral health care guideline for institutionalized older people has been available. For that reason, the Dutch Association of Nursing Home Physicians developed the Oral health care Guideline for Older people in Long-term care Institutions (OGOLI), meeting the requirements of the AGREE instrument for assessing a guideline's quality. This short report presents the keynotes and the content of the Oral health care Guideline. Most recommendations are based on expert opinions. Only 4 recommendations (education, pneumonia, use of an electric toothbrush, and fluoride rinsing in case of a sudden increase of oral plaque amount) are based on evidence level A2 conclusions. This emphasizes the need for further research on oral health of institutionalized older people. PMID- 22092289 TI - Sergei Winogradsky: a founder of modern microbiology and the first microbial ecologist. AB - Sergei Winogradsky, was born in Russia in 1856 and was to become a founder of modern microbiology. After his Master's degree work on the nutrition and growth physiology of the yeast Mycoderma vini at the University of St. Petersburg, he joined the laboratory of Anton DeBary in Strassburg. There he carried out his studies on the sulfur-oxidizing bacterium Beggiatoa which resulted in his formulation of the theory of chemolithotrophy. He then joined the Swiss Polytechnic Institute in Zurich where he did his monumental work on bacterial nitrification. He isolated the first pure cultures of the nitrifying bacteria and confirmed that they carried out the separate steps of the conversion of ammonia to nitrite and of nitrite to nitrate. This led directly to the concept of the cycles of sulfur and nitrogen in Nature. He returned to Russia and there was the first to isolate a free-living dinitrogen-fixing bacterium. In the flush of success, he retired from science and spent 15 years on his familial estate in the Ukraine. The Russian revolution forced him to flee Russia. He joined the Pasteur Institute in Paris where he spent his remaining 24 years initiating and developing the field of microbial ecology. He died in 1953. PMID- 22092290 TI - Measurement of vascular tone and stroke volume baroreflex gain. AB - The arterial baroreflex system (BRS) consists of at least three closed-loop control systems: the heart rate (HR), vascular tone (VT), and stroke volume (SV) BRSs. Whereas HR-BRS gain is well studied, VT-BRS and SV-BRS gain are not. This study aimed to develop a method for quantifying VT-BRS and SV-BRS gain using an established HR-BRS gain measurement approach. ECG and beat-to-beat blood pressure (BP) were recorded in 31 young healthy participants during three tasks. Sequences of R-to-R wave intervals (RRI) of the ECG, pulse transit time (PTT), and SV were measured to assess HR-, VT-, and SV-BRS gain using the cross-spectral technique of computing the BP-RRI, BP-PTT, and BP-SV transfer functions. Gain in each BRS arch was measured in individuals with intact BRS functioning. Functional overlap and independence was noted in the BRS arches. The implications of the proposed method are discussed. PMID- 22092292 TI - Applying the PRECIS criteria to describe three effectiveness trials of weight loss in obese patients with comorbid conditions. AB - OBJECTIVES: To characterize Practice-Based Opportunities for Weight Reduction (POWER) trials along the pragmatic-explanatory continuum. SETTINGS: The POWER trials consist of three individual studies that target obesity treatment in primary care settings. DESIGN: Using the PRagmatic Explanatory Continuum Indicator Summary (PRECIS) criteria, nine reviewers independently scored each trial. METHODS: Average and median ratings, inter-rater reliability, and relationships to additional ratings of the extent to which study designs were explanatory (i.e., efficacy) versus pragmatic (i.e., practical) and related to external validity were determined. PRINCIPAL FINDINGS: One trial was consistently rated as being significantly more pragmatic than the others (R(2) =0.43, p< .001), although all three were in the moderate range on the PRECIS scales. Ratings varied across PRECIS dimensions, being most pragmatic on comparison condition and primary outcome. Raters, although undergoing training and using identical definitions, scored their own study as more pragmatic than the other studies/interventions. CONCLUSIONS: These results highlight the need for more comprehensive reporting on PRECIS and related criteria for research translation. The PRECIS criteria provide a richer understanding of the POWER studies. It is not clear whether the original criteria are sufficient to provide a comprehensive profile. PMID- 22092293 TI - Genetic characterization of denitrifier communities with contrasting intrinsic functional traits. AB - Microorganisms capable of denitrification are polyphyletic and exhibit distinct denitrification regulatory phenotypes (DRP), and thus, denitrification in soils could be controlled by community composition. In a companion study (Dorsch et al., 2012) and preceding work, ex situ denitrification assays of three organic soils demonstrated profoundly different functional traits including N(2) O/N(2) ratios. Here, we explored the composition of the underlying denitrifier communities by analyzing the abundance and structure of denitrification genes (nirK, nirS, and nosZ). The relative abundance of nosZ (vs. nirK + nirS) was similar for all communities, and hence, the low N(2) O reductase activity in one of the soils was not because of the lack of organisms with this gene. Similarity in community composition between the soils was generally low for nirK and nirS, but not for nosZ. The community with the most robust denitrification (consistently low N(2) O/N(2) ) had the highest diversity/richness of nosZ and nirK, but not of nirS. Contrary results found for a second soil agreed with impaired denitrification (low overall denitrification activity, high N(2) O/N(2) ). In conclusion, differences in community composition and in the absolute abundance of denitrification genes clearly reflected the functional differences observed in laboratory studies and may shed light on differences in in situ N(2) O emission of the soils. PMID- 22092294 TI - Analgesia and sedation of mechanically ventilated patients - a national survey of clinical practice. AB - BACKGROUND: The importance of balanced sedation and pain treatment in intensive care units (ICUs) is evident, but regimes and use of medication differ widely. Previous surveys have focused on the use of various medications and regimes. What has not been explored is the process by which nurses and physicians assess patients' needs and work together toward a defined level of sedation and pain for the ICU patient. The purpose of the study was to determine the use of protocols and medications for sedation and analgesia in Norwegian ICUs and the degree of cooperation between nurses and physicians in using them. METHODS: A national survey was conducted in autumn 2007, using postal self-administered questionnaires. RESULTS: Written pain treatment and sedation protocols were not routinely used in Norwegian ICUs; however, half of the departments titrated sedation according to a scoring system, most commonly the Motor Activity Assessment Score. The most commonly used sedatives were propofol and midazolam, while fentanyl and morphine were the most used analgesics. The majority of respondents were concerned about the side effects of sedation and analgesics, leading to circulatory instability and delayed awakening. Nurses and physicians agreed upon the main indications for sedation: patient tolerance for ventilation, tolerance for medical and nursing interventions, and patient symptoms. CONCLUSIONS: Potential factors which may improve sedation and pain management of mechanically ventilated patients in Norwegian ICUs are more systematic assessments of pain and sedation, and the use of written protocols. Strategies which reduce side effects should be addressed. PMID- 22092296 TI - The effect of clockwise and counterclockwise twisting moments on abutment screw loosening. AB - OBJECTIVES: Abutment screw loosening is one of the most common complications of dental implants. When occlusal loading is applied, bending and twisting moments are counteracted by the implant-abutment connection held with the abutment screw. Restorations in different quarters of the oral cavity might bear clockwise or counterclockwise twisting moments that result from a regular chewing pattern. The aim of this study was to investigate the effect of different directional twisting moments on abutment screws. METHODS: Twenty 3i implants were divided into four groups of C, R, L, and O. Each assembly consisted of an implant, abutment, and superstructure. For group C, a cyclic load of 10-100 N for 10(6) cycles was applied centrally and perpendicular to the long axis of the implant, whereas for groups R and L, the same load conditions were applied eccentrically in clockwise and counterclockwise directions, respectively. Group O was left unloaded. The difference between the initial torque and post-load reverse torque was defined as the total torque loss. The data were analyzed by Kruskal-Wallis test. The surface of the abutment hexagon corners were examined with SEM after loading. RESULTS: No abutment screw loosening was found after loading. Total torque loss of groups C, R, L, and O were 10.50 +/- 0.58, 9.56 +/- 1.01, 9.98 +/- 1.81, and 9.58 +/- 0.94 Ncm, respectively. There were no statistical differences among the four groups. SEM observations showed marked burnishing at the hexagonal corners on the compression sides of the R and L groups. CONCLUSIONS: Within the limitations of this study, there was little effect of twisting moment direction on the total torque loss of an internal hexagon connection implant system. This could be attributed to the anti-twisting mechanism of the internal hexagon connection. PMID- 22092295 TI - Personal use of complementary and alternative medicine (CAM) by U.S. health care workers. AB - OBJECTIVE: To examine personal use of complementary and alternative medicine (CAM) among U.S. health care workers. DATA: Data are from the 2007 Alternative Health Supplement of the National Health Interview Survey. We examined a nationally representative sample of employed adults (n = 14,329), including a subsample employed in hospitals or ambulatory care settings (n = 1,280). STUDY DESIGN: We used multivariate logistic regression to estimate the odds of past year CAM use. PRINCIPAL FINDINGS: Health care workers are more likely than the general population to use CAM. Among health care workers, health care providers are more likely to use CAM than other occupations. CONCLUSIONS: Personal CAM use by health care workers may influence the integration of CAM with conventional health care delivery. Future research on the effects of personal CAM use by health care workers is therefore warranted. PMID- 22092297 TI - Increased risk for post-operative corneal injuries in patients who undergo laparoscopic gynecologic surgery. AB - BACKGROUND: The objective of this study was to verify whether or not the incidence of post-operative corneal injuries (PCIs) in patients who undergo laparoscopic gynecologic surgery is higher than patients who undergo non laparoscopic gynecologic surgery. METHODS: The peri-operative variables were extracted from the medical records of patients who underwent gynecologic surgery under general anesthesia at our institute between January 2004 and June 2010. The extracted variables were age, day of week of surgery, type of surgery (laparoscopy vs. non-laparoscopy), surgical scheduling (elective vs. emergent), pre-operative hemoglobin, surgery time, peri-operative transfusions, and PCIs. The association of peri-operative variables with PCIs was examined using univariate and multivariate analyses. RESULTS: A total of 6992 consecutive patients were included in this study. PCIs occurred in 23 patients (0.3%). Based on univariate analysis, the type of surgery and surgery times were associated with PCIs. Based on multivariate analysis, laparoscopy and lengthy surgery times significantly increased the risk for PCIs. The median duration of PCI symptoms was 3 days (range, 1-11 days); no patient had long-term sequalae. CONCLUSION: Laparoscopic gynecologic surgery increases the incidence of PCI compared with non laparoscopic gynecologic surgery. PMID- 22092298 TI - Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects. AB - AIMS: To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4 mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. METHODS: Ten methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6 glucuronides and codeine-6-glucuronide. RESULTS: The urinary metabolic ratio for O-demethylation was significantly higher (P= 0.0044) in the subjects taking methadone (mean +/- SD, 2.8 +/- 3.1) compared with those taking buprenorphine (0.60 +/- 0.43), likewise for 6-glucuronide formation (0.31 +/- 0.24 vs. 0.053 +/ 0.027; P < 0.0002), but there was no significant difference (P= 0.36) in N demethylation. Similar changes in plasma metabolic ratios were also found. In plasma, compared with those maintained on buprenorphine, the methadone-maintained subjects had increased codeine and norcodeine concentrations (P < 0.004), similar morphine (P= 0.72) and lower morphine-3- and -6- and codeine-6-glucuronide concentrations (P < 0.008). CONCLUSION: Methadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6. PMID- 22092299 TI - Thiamine plays a critical role in the acid tolerance of Listeria monocytogenes. AB - Understanding the molecular basis of acid tolerance in the food-borne pathogen Listeria monocytogenes is important as this property contributes to survival in the food-chain and enhances survival within infected hosts. The aim of this study was to identify genes contributing to acid tolerance in L. monocytogenes using transposon mutagenesis and subsequently to elucidate the physiological role of these genes in acid tolerance. One mutant harboring a Tn917 insertion in the thiT gene (formerly lmo1429), which encodes a thiamine (vitamin B1) uptake system, was found to be highly sensitive to acid. The acid-sensitive phenotype associated with loss of this gene was confirmed with an independently isolated mutant, from which the thiT gene was deleted (?thiT). Cells of both wild-type and ?thiT mutant that were thiamine depleted were found to be significantly more acid sensitive than control cultures. Thiamine-depleted cultures failed to produce significant concentrations of acetoin, consistent with the known thiamine dependence of acetolactate synthase, an enzyme required for acetoin synthesis from pyruvate. As acetoin synthesis is a proton-consuming process, we suggest that the acid sensitivity observed in thiamine-depleted cultures may be owing to an inability to produce acetoin. PMID- 22092300 TI - Effect of implant-abutment connection design on reliability of crowns: regular vs. horizontal mismatched platform. AB - OBJECTIVES: To evaluate the reliability and failure modes of regular and horizontal mismatched platforms for implant-abutment connection varying the implant diameter. MATERIAL AND METHODS: Regular (REG, n = 21, 4.0-mm-diameter implant) and horizontal mismatched (HM, n = 21, 4.6-mm-diameter implant) platform Ti-6Al-4V implants were restored with proprietary identical Ti-6Al-4V abutments and metal crowns (cobalt-chrome, Wirobond 280, BEGO, Bremen, Germany) cemented. Mechanical testing comprised step-stress accelerated-life testing, where crowns were distributed in three loading profiles for fatigue in water, producing timely and clinically relevant fractures. The probability of failure vs. cycles (95% two sided confidence intervals) was calculated and plotted using a powerlaw relationship for damage accumulation, Weibull modulus (95% two-sided confidence intervals) and then the reliability for a mission of 50,000 cycles at 125 N load (95% two-sided confidence interval) were calculated. Fractography was performed in the scanning electron microscope. RESULTS: The beta-value for group REG (beta = 1.37) indicated that fatigue was a factor accelerating the failure, whereas load alone dictated the failure for group HM (beta = 0.71). The Weibull parameter contour plot showed no significantly different Weibull modulus for REG (10.24) compared to HM (10.20) and characteristic strength of 162.6 and 166.8 N, respectively (P > 0.91). The calculated reliability for a mission of 50,000 cycles at 125 N load was not significantly different (0.71 for REG and 0.73 for HM). Abutment screw failure was the chief failure mode. CONCLUSIONS: Reliability was not significantly different between groups and failure modes were similar. PMID- 22092301 TI - The influence of color on emotional perception of natural scenes. AB - Is color a critical factor when processing the emotional content of natural scenes? Under challenging perceptual conditions, such as when pictures are briefly presented, color might facilitate scene segmentation and/or function as a semantic cue via association with scene-relevant concepts (e.g., red and blood/injury). To clarify the influence of color on affective picture perception, we compared the late positive potentials (LPP) to color versus grayscale pictures, presented for very brief (24 ms) and longer (6 s) exposure durations. Results indicated that removing color information had no effect on the affective modulation of the LPP, regardless of exposure duration. These findings imply that the recognition of the emotional content of scenes, even when presented very briefly, does not critically rely on color information. PMID- 22092302 TI - Healing outcomes at implants installed in grafted sites: an experimental study in dogs. AB - AIM: To evaluate the integration of implants installed using a surgical guide in augmented sites with autologous bone or deproteinized bovine bone mineral (DBBM) blocks, concomitantly with a collagen membrane. MATERIAL AND METHODS: Mandibular molars were extracted bilaterally in six Labrador dogs, the buccal bony wall was removed, and a box-shaped defect was created. After 3 months, flaps were elevated, a bony graft was harvested from the ascending ramus, and secured to the lateral wall of the defect by means of screws. In the left mandibular side, a DBBM block was fixed into the defect. A resorbable membrane was applied at both sides, and the flaps were sutured. After 3 months, flaps were elevated, and a customized device was used as surgical guide to prepare the recipient sites in the interface between grafts and parent bone. One implant was installed in each side of the mandible. After 3 months, biopsies were harvested, and ground sections were prepared for histologic evaluation. RESULTS: One autologous bone block graft was lost before implant installation. The width of the alveolar crest at the test sites (DBBM) was 5.4 +/- 1.2 mm before, 9.4 +/- 1.2 mm immediately after grafting, and 9.3 +/- 1 mm at implant installation. At the control sites (autologous bone), the corresponding values were: 5.2 +/- 1, 9 +/- 1.2, and 8.7 +/- 0.9 mm, respectively. All implants installed were available for histologic evaluation (n = 5). The autologous bone grafts, rich in vessels and cells, were integrated in the parent bone, and only little non-vital bone was found. The BIC% was 56.7 +/- 15.6% and 54.2 +/- 13.2% at the buccal and lingual aspects, respectively. At the test sites, the DBBM appeared to be embedded into connective tissue, and very little newly formed bone was encountered within the grafts. The BIC% was 5.8 +/- 12.3% and 51.3 +/- 14.2% at the buccal and lingual aspects, respectively. CONCLUSIONS: Autologous bone blocks used to augment the alveolar bony crest horizontally allowed the complete osseointegration of implants installed after 3 months of healing. However, similar blocks of DBBM did not promote osseointegration, although the installed implants were stable owing to the osseointegration in the sites of the parent bone. PMID- 22092303 TI - Retention of implant-supported zirconium oxide ceramic restorations using different luting agents. AB - OBJECTIVE: The aim of this study was to evaluate the retention value of implant supported zirconium oxide ceramic copings using different luting agents. METHOD AND MATERIALS: Twenty ITI solid abutments of 5.5 mm height and ITI implant analogs were mounted vertically into autopolymerizing acrylic resin blocks. Ninety zirconium oxide copings (Cercon, Degudent) with a loop on the occlusal portion were made. All samples were airborne particle abraded with 110 MUm Al2O3 and luted using different types of luting agents: resin cements (Clearfil SA, Panavia F2.0, Fuji Plus), conventional cements (Fleck's, Poly F, Fuji I), and temporary cements (Temp Bond, GC free eugenol, TempSpan) with a load of 5 Kg. (N = 10) All copings were incubated at 37 degrees C for 24 h and conditioned in artificial saliva for 1 week, and thermal cycled for 5000 cycles 5-55 degrees C with a 30-s dwell time. The dislodging force of the copings along the long axis of the implant-abutment complex was recorded using universal testing machine with 5 mm/min crosshead speed. Data were subjected to Kruskal-Wallis (alpha = 0.05) and Mann-Whitney tests with Bonferroni step down correction (alpha = 0.001). RESULTS: There was significant difference between the mean rank retention values of different luting agents (P < 0.001). The resin cements showed the highest retention (Clearfil SA, 203.49 +/- 52.86; Fuji Plus, 190.61 +/- 48.00; Panavia F 2.0, 172.16 +/- 70.76 N). The conventional cements had more retention than the temporary cements and glass ionomer cement (P < 0.001). CONCLUSION: The retention of zircona ceramic restorations, over ITI solid abutments may be influenced by the type of cement. The application of an MDP-containing resin and resin-modified glass ionomer luting agents increase the retentive value of implant-supported zirconium oxide restorations. PMID- 22092304 TI - Species composition and cyanotoxin production in periphyton mats from three lakes of varying trophic status. AB - In lakes, benthic micro-algae and cyanobacteria (periphyton) can contribute significantly to total primary productivity and provide important food sources for benthic invertebrates. Despite recognition of their importance, few studies have explored the diversity of the algal and cyanobacterial composition of periphyton mats in temperate lakes. In this study, we sampled periphyton from three New Zealand lakes: Tikitapu (oligotrophic), Okareka (mesotrophic) and Rotoiti (eutrophic). Statistical analysis of morphological data showed a clear delineation in community structure among lakes and highlighted the importance of cyanobacteria. Automated rRNA intergenic spacer analysis (ARISA) and 16S rRNA gene clone libraries were used to investigate cyanobacterial diversity. Despite the close geographic proximity of the lakes, cyanobacterial species differed markedly. The 16S rRNA gene sequence analysis identified eight cyanobacterial OTUs. A comparison with other known cyanobacterial sequences in GenBank showed relatively low similarities (91-97%). Cyanotoxin analysis identified nodularin in all mats from Lake Tikitapu. ndaF gene sequences from these samples had very low (<= 89%) homology to sequences in other known nodularin producers. To our knowledge, this is the first detection of nodularin in a freshwater environment in the absence of Nodularia. Six cyanobacteria species were isolated from Lake Tikitapu mats. None were found to produce nodularin. Five of the species shared low (< 97%) 16S rRNA gene sequence similarities with other cultured cyanobacteria. PMID- 22092306 TI - Intravenous injection of autologous amniotic fluid induces transient thrombocytopenia in a gravid rabbit model of amniotic fluid embolism. AB - BACKGROUND: Amniotic fluid embolism (AFE) is a rare but catastrophic complication of pregnancy characterized by severe hypotension, cardiovascular collapse, and massive consumptive coagulopathy. Several animal models of this syndrome have been proposed, but most have yielded inconclusive results. OBJECTIVES: The objective of this study was to develop a suitable animal model of AFE. METHODS: Twelve rabbits in late gestation (25 days) were used. Amniotic fluid was collected from the fetal amniotic sacs after laparotomy, and autologous fluid was injected into 6 rabbits via the left auricular vein. Six other rabbits received saline (control group). Blood pressure, platelet counts, and coagulation variables were measured at baseline and at various intervals for 60 minutes after injection. The in vitro effect of amniotic fluid on coagulation was assessed by thrombelastographic (TEG) analysis. RESULTS: Injection of amniotic fluid did not reproduce clinical signs of AFE and had no effect on activated partial thromboplastin time (aPTT), prothrombin time (PT), or Factor VIII activity. However, significant thrombocytopenia was observed 5 minutes after administration of amniotic fluid and resolved by 60 minutes. In vitro addition of amniotic fluid to blood resulted in accelerated clotting on TEG tracings. CONCLUSIONS: The syndrome of AFE was not reproduced in this rabbit model. However, injection of autologous amniotic fluid induced a transient and severe thrombocytopenia. Moreover, TEG analysis indicated that amniotic fluid could initiate the coagulation cascade. Other factors such as the presence of meconium in amniotic fluid may be needed to provoke more severe clinical signs. PMID- 22092307 TI - Evidence to inform policy, practice and education for unintended pregnancy prevention and management. PMID- 22092308 TI - Hip strength assessment using handheld dynamometry is subject to intertester bias when testers are of different sex and strength. AB - Handheld dynamometry (HHD) is a promising tool for obtaining reliable hip strength measurements in the clinical setting, but intertester reliability has been questioned, especially in situations where testers exhibit differences in upper-extremity muscle strength (male vs female). The purpose of this study was to examine the intertester reliability concerning strength assessments of hip abduction, adduction, external and internal rotation, flexion and extension using HHD, and to test whether systematic differences in test values exist between testers of different upper-extremity strength. Fifty healthy individuals (29 women), aged 25 +/- 5 years were included. Two physiotherapist students (one female, one male) of different upper-extremity strength performed the measurements. The tester order and strength test order were randomized. Intraclass correlation coefficients were used to quantify reliability, and ranged from 0.82 to 0.91 for the six strength test. The female tester systematically measured lower strength values for all isometric strength tests (P < 0.05). In hip strength assessments using HHD, systematic bias exists between testers of different sex, which is likely explained by differences in upper-extremity strength. Hence, to improve intertester reliability, the dynamometer likely needs external fixation, as this will eliminate the influence of differences in upper extremity strength between testers. PMID- 22092309 TI - Relationship between magnitude of immediate loading and peri-implant osteogenesis in dogs. AB - OBJECTIVES: The purpose of this study was to investigate the influence of the magnitude of immediate loading on peri-implant bone in an animal model of dental implantation. MATERIAL AND METHODS: Eight weeks after the extraction of maxillary and mandibular premolars, three implants were inserted bilaterally in the mandibles of six Beagle dogs. One implant was unloaded (UL) as a control, and two implants were loaded immediately with 10 N (mild loading: ML) or 50 N (excessive loading: EL) laterally using a cyclic loading device twice a week for 3 weeks. Fluorescent bone markers were injected to examine bone formation around the implants. The animals were sacrificed 3 weeks after implantation. Peri-implant osteogenesis was assessed by histomorphometric procedures, i.e., measuring bone implant contact (BIC) and bone density (BD). RESULTS: The UL and ML groups had no peri-implant infection, and newly formed bone was observed over a wide area from the implant neck toward the tip, and in direct contact with the implant surface. In contrast, in the EL group, newly formed bone was rarely observed around the implant neck and there were signs of infection. Both BIC and BD in the ML group were significantly greater than those in the other groups. BIC and BD in the EL group were significantly lower than those in the other groups. CONCLUSION: A suitable magnitude of load applied immediately after dental implantation promotes peri-implant osteogenesis. PMID- 22092310 TI - AT-rich region and repeated sequences - the essential elements of replication origins of bacterial replicons. AB - Repeated sequences are commonly present in the sites for DNA replication initiation in bacterial, archaeal, and eukaryotic replicons. Those motifs are usually the binding places for replication initiation proteins or replication regulatory factors. In prokaryotic replication origins, the most abundant repeated sequences are DnaA boxes which are the binding sites for chromosomal replication initiation protein DnaA, iterons which bind plasmid or phage DNA replication initiators, defined motifs for site-specific DNA methylation, and 13 nucleotide-long motifs of a not too well-characterized function, which are present within a specific region of replication origin containing higher than average content of adenine and thymine residues. In this review, we specify methods allowing identification of a replication origin, basing on the localization of an AT-rich region and the arrangement of the origin's structural elements. We describe the regularity of the position and structure of the AT-rich regions in bacterial chromosomes and plasmids. The importance of 13-nucleotide long repeats present at the AT-rich region, as well as other motifs overlapping them, was pointed out to be essential for DNA replication initiation including origin opening, helicase loading and replication complex assembly. We also summarize the role of AT-rich region repeated sequences for DNA replication regulation. PMID- 22092311 TI - Caring for smiles--a new educational resource for oral health training in care homes. PMID- 22092312 TI - Delivering and securing health care in challenging times. PMID- 22092313 TI - Plagiarism or differing ways of representing knowledge? PMID- 22092314 TI - Promoting access to health care: a nursing role and responsibility. PMID- 22092318 TI - Many paths lead to nursing: factors influencing students' perceptions of nursing. AB - BACKGROUND: A diverse group of students is being recruited to nursing programmes worldwide, although little research has identified the effect of this diversity. Contemporary knowledge of the qualities of nurses and how they vary with demographic and other factors may assist in the retention of nursing students. AIM: The aim of this study is to explore student nurses' perceptions of the qualities of nurses and how these differ with age, country of birth, gender, healthcare experience and mode of entry to the nursing programme. METHODS: Using a descriptive comparative design, 676 nursing students in their first week of a Bachelor of Nursing programme participated (77% response). Participants completed a survey noting demographic data such as age, gender, healthcare experience, country of birth, nursing programme entry method and attributes of nurses from the valid and reliable Qualities of Nursing Scale (QoN). RESULTS: Overall, the students confirmed their agreement with the 12 items of the QoN and rated good listening skills as the most important quality for a nurse rather than Caring or Helping. Male participants and participants born overseas demonstrated the lowest mean scores on most qualities, suggesting less agreement with the qualities. DISCUSSION: The recruitment of students to university needs to continue to support disparate entry pathways. Students with more life experience (older students) or health experience may be more likely to complete nursing courses and to be retained within health services. Qualities of nurses may be changing to reflect modern perceptions of nurses with a shift away from the focus on caring. PMID- 22092319 TI - Nursing students' perceptions of nursing: a descriptive study of four cohorts. AB - AIMS: The study aims to describe nursing students' changing perception of nursing over 4 years of the nursing programme and examine whether perception differed by gender, previous study or choice of nursing education. METHODS: A descriptive cross-sectional design was used, with a probability sample of 606 students. Respondents were a random sample of 50% of each of the four educational cohorts studying within the academic year 2008-2009 in one baccalaureate nursing programme at a Jordanian public university. A specifically designed tool of statements of nursing definitions based on nursing theories, the nursing literature and sociocultural beliefs was used to identify student nurses' perception of nursing. FINDINGS: Student perceptions changed from lay altruistic beliefs of nursing to theoretical medical technological views of the profession denoting a theory-practice gap. Perceptions also differed by gender, having a previous associate degree in nursing and a priority choice to study nursing. CONCLUSION: Such results delineated the importance of revising nursing schools' curricula and the universities' admission policies into the nursing profession. PMID- 22092320 TI - Exchange students crossing language boundaries in clinical nursing practice. AB - AIM: This article examines challenges and learning outcomes for nursing students from a Central European university of applied sciences who completed 3 months of clinical practice in Norway. The clinical practice was supervised in English by Norwegian nurses and nursing teachers. English is not the primary language in any of the countries. BACKGROUND: Increases in global migration have contributed to the need for an international dimension in nursing education. Personal mobility is a crucial part of the European Union's goal of becoming a knowledge society. Clinically based experiences pose challenges that are additional to and often more complex than traditional course-based experiences. Students who come from a non-English-speaking country for clinical practice in Norway face challenges regarding language. Accepting incoming students is a way of achieving higher quality and more relevant education in nursing. FINDINGS: The study shows that clinical practice in a foreign country gives added value compared with clinical practice at home. Greater self-confidence and understanding of core concepts in nursing is described by the participants. Language differences are not regarded as a problem but as a way of developing personal and professional competence. The ability to compare healthcare systems in the two counties is important in developing competencies in nursing. PMID- 22092321 TI - Patient safety: nursing students' perspectives and the role of nursing education to provide safe care. AB - BACKGROUND AND AIM: Nurses as the largest group of healthcare providers are in the best position to improve patient safety. In preparing future nurses, nurse educators have an important role in developing the knowledge, skills and attitudes among nursing students related to patient safety. The aim of this study was to explore Iranian nursing students' perspectives regarding patient safety and the role of nursing education in developing their capabilities to provide safe care. METHODS: A purposeful sampling strategy was used to recruit 17 junior and senior nursing students for qualitative, semi-structured interviews. Content analysis of the interview transcripts was conducted to identify several relevant themes. FINDINGS: Three main themes emerged from the data analysis: 'safety as patient comfort', 'not being knowledgeable or experienced enough' and 'being helped to internalise the principles and values of patient safety'. The third theme consisted of two categories: 'adopting a humanistic approach towards patients' and 'practising conscientiously in the workplace'. CONCLUSION: The present study adds insights on how nursing students understand and may be helped to internalise concepts of patient safety within their practice. Nursing education curriculum designers need to go beyond theoretical concepts of patient safety education and devise strategies to increase the application of safety knowledge and competencies in nursing practice. PMID- 22092322 TI - Children's knowledge of cancer diagnosis and treatment: Jordanian mothers' perceptions and satisfaction with the process. AB - BACKGROUND: The amount of information shared with children regarding their illness, as well as what knowledge children are entitled to know, varies widely among cultures. AIMS: This study aims to examine mothers' accounts of communication about cancer diagnosis to their children, how much children knew about their illnesses and how satisfied the mothers were with the method they used in communicating the diagnosis. METHODS: Using semi-structured interviews and open-ended questions, 51 mothers attending paediatric oncology clinics in Jordan were interviewed. Content analysis was used to analyse the data. FINDINGS: Mothers expressed a range of views about the forms of disclosure, including being clear about the diagnosis and its treatment and being secretive yet misconceptualizing the accounts of the illness. The median age for the children diagnosed with cancer was 11 years (interquartile range 7-16 years). Most of the mothers were offered no help with talking to their children about cancer diagnosis. Mothers who found it difficult to tell the news of the diagnosis to their children finally withheld the diagnoses from them. Those same mothers were unhappy and uncomfortable with the communication method they had used with children. CONCLUSION: This study emphasized the role of nurses' interaction with their child patients diagnosed with cancer. Nurses should not have an opinion about how and what children need to know about their illness, and preferably should take an active role in the process of communication between mothers and their children. Further work and research are needed in this field. PMID- 22092323 TI - The breast care nurse: the care specialist in breast centres. AB - BACKGROUND: In Europe, breast cancer is the most common form of cancer in women; 26.5 per cent of all new malignant diseases and 17.5 per cent of all cancer deaths are due to this type of cancer. In Germany, approximately every tenth woman is diagnosed with breast cancer during her lifetime. OBJECTIVE: In order to increase the quality of life of breast cancer patients, the European Society of Mastology (EUSOMA) requires the availability of, and an integration of qualified and specialized care into the interdisciplinary team. Thus, in Germany, a new type of job profile for 'breast nurse' as a qualified care specialist has to be established and has to be oriented towards the international standards of a breast care nurse (BCN). METHODS: The Charite's Academy of Health--in cooperation with the Interdisciplinary Breast Centre of the Charite--has offered a career advisory service curriculum for the BCN since 2006 in accordance with the EUSOMA guidelines. RESULTS: In three courses, 45 BCNs have been trained. In the first refresher seminar in May 2009, the BCNs were given an opportunity to exchange with fellow BCNs their experiences. CONCLUSION: We were able to set up a new curriculum to train nurses as BCNs as to improve the quality of care for breast cancer patients and to orientate the training towards the international standards of a BCN qualification. PMID- 22092324 TI - Occupational exposure to HIV: a conflict situation for health workers. AB - AIM: To determine the frequency of occupational exposure to human immunodeficiency virus (HIV), the circumstances and predisposing factors, the high-risk groups, the extent to which exposures are reported and the post exposure prophylaxis (PEP) utilized by health-care workers (HCWs) and students in a Ugandan hospital. BACKGROUND: Occupational exposure to HIV is a low but potential risk of HIV infection to health workers. METHOD: Self-administered questionnaire was given to 224 participants (including 98 HCWs and 126 students) in Mbarara Hospital, Uganda. Data were analysed with descriptive statistics using the Statistical Package for the Social Sciences version 15.0 (SPSS Inc, Chicago, IL, USA). FINDINGS: Of the 224 participants surveyed, 19.2% reported having sustained injection needle stick injuries in the previous year, of which 4.46% occurred with HIV-infected blood. Other reported injuries were cannula needle stick injury (0.89%), suture needle stick injuries (3.13%), scalpel cut injuries (0.45%) and muco-cutaneous contamination (10.27%). The most affected groups were nurses-midwives for scalpel injuries and students for stick injuries. The predisposing factors reported included lack of protective devices and recapping of needles. Exposures were under-reported. Uptake of PEP was also low. CONCLUSION: Occupational exposure to HIV presents a conflict situation for HCWs. It remains a frequent occurrence particularly among student nurses-midwives, despite being avoidable. Its prophylactic treatment is hampered by poor reporting and investigation of exposures, and poor access to PEP. Strict adherence to universal precaution and proper handling of occupational exposure to HIV should be encouraged. PMID- 22092325 TI - Factors affecting peritoneal dialysis selection in Taiwanese patients with chronic kidney disease. AB - BACKGROUND: Taiwan has the highest incidence and prevalence of end-stage renal disease (ESRD) in the world with 55,499 ESRD patients on long-term dialysis. Nevertheless, 90.96% of these patients are managed on maintenance haemodialysis (HD), with only 9.03% enrolled in a peritoneal dialysis (PD) programme. AIM: The study aim was to identify the factors affecting Taiwanese patient's selection of PD in preference to HD for chronic kidney disease. METHODS: A cross-sectional research design was utilized with 130 chronic renal failure (CRF) patients purposively selected from outpatient nephrology clinics at four separate Taiwan hospitals. Logistic regression was used to identify the main factors affecting the patient's choice of dialysis type. RESULTS: Single-factor logistic regression found significant differences in opinion related to age, education level, occupation type, disease characteristics, lifestyle modifications, self-care ability, know-how of dialysis modality, security considerations and findings related to the decisions made by medical personnel (P < 0.05). Moreover, multinomial logistic regression after adjustment for interfering variables found that self-care ability and dialysis modality know-how were the two main factors affecting the person's selection of dialysis type. CONCLUSIONS: Self-care ability and the person's knowledge of the different types of dialysis modality and how they function were the major determinants for selection of dialysis type in Taiwan based on the results from this study. The results indicate that the education of CRF patients about the types of dialysis available is essential to enable them to understand the benefits or limitations of both types of dialysis. PMID- 22092326 TI - Factors associated with delayed hospital arrival among patients with acute myocardial infarction: a cross-sectional study in Greece. AB - BACKGROUND: It is proven that early admission to hospital contributes significantly to the successful management of acute myocardial infarction (AMI). AIM: This study aimed to examine the factors associated with delayed hospital arrival among patients with AMI. METHODS: A cross-sectional study among 477 AMI patients was conducted during a 2-year period in two large tertiary hospitals in Greece. Structured face-to-face interviews were conducted and information regarding their socio-demographic characteristics, medical history and factors that might be correlated with delayed hospital arrival were collected. RESULTS: The main factors that were found to be correlated with delayed hospital arrival among AMI patients were the absence of companion/attendant/escort present during the AMI [odds ratio (OR) 2.1, 95% confidence interval (CI) 0.98-4.4, P = 0.049], previous medical history of diabetes mellitus (OR 3.4, CI 1.6-7.2, P = 0.002), absence of dyspepsia (OR 9.2, CI 3.6-23.3, P < 0.001) and nausea/vomiting symptoms (OR 16.9, CI 4.1-69.1, P < 0.001), and also being at a distance of more than 10 km from the hospital (OR 19.6, CI 5.4-70.6, P < 0.001). CONCLUSION: A number of factors that might delay hospital arrival among patients with AMI should be taken into account in healthcare service planning. Health policy actions that will improve the accessibility to healthcare services, the restructuring of the Greek primary healthcare system and the provision of effective patient education by nurses could reduce the pre-hospital delay. LIMITATIONS: The study was conducted in two hospitals which limits the generalization of the findings. Also, the onset of AMI symptoms relied on self report by the patients. PMID- 22092327 TI - Condom promotion in Belize: self-efficacy of Belizean nurses. AB - BACKGROUND: Outside of abstinence, correct and consistent condom use is the single most effective tool to prevent the transmission human immunodeficiency virus (HIV). This is particularly true in countries such as Belize where incidence rates remain high. Women are physiologically at higher risk for HIV, and many feel powerless to insist on condom use. Although nurses are in a position to promote condom use, variables that influence this decision are not clearly understood. In this study, we examined variables that influence a nurses' self-efficacy to promote and teach condom use to women specifically to reduce their HIV risk. METHODS: Data related to self-efficacy, vicarious experience related to condom use promotion and a nurse's sexual relationship power were collected from nurses practising in Belize (n = 60). These data were cross sectional and collected at the annual nurses' conference. RESULTS: Both years of nursing education and positive vicarious experience promoting and teaching condom use to women were positively correlated to their self-efficacy to do so. Vicarious experience was significantly correlated to self-efficacy in a subgroup of nurses with lower sexual relationship power but not in those with higher sexual relationship power. CONCLUSIONS: When designing HIV continuing education programmes for nurses in Belize, it is important to consider level of nursing education and access to vicarious experience such as mentoring and role modelling. An additional factor to consider is the influence that a nurse's power in her own primary sexual relationship may play in the formation of her self efficacy. PMID- 22092328 TI - Religion, culture and male involvement in the use of the Standard Days Method: evidence from Enugu and Katsina states of Nigeria. AB - AIM: This paper presents findings from an exploratory study on the use of the Standard Days Method(r) (SDM) of family planning (FP) in Katsina and Enugu states of Nigeria. BACKGROUND: Potential users of FP often do not use modern methods if its practice is in dissonance with cultural and religious values. Increasing FP options through the introduction of effective natural methods is important, as it will ensure that FP providers, particularly nurses, can provide appropriate non hormonal methods to women who are interested in their use. This will bring about an increased contraceptive prevalence in countries with strong religious barriers to modern FP methods. METHODS: A qualitative study using focus group discussions and in-depth interviews was conducted with nurses, community FP providers and users of the SDM following the introduction of the method in two Nigerian states. DISCUSSION: Both users and providers perceive the SDM to be religiously and culturally acceptable. They found it useful particularly among women who could not use hormonal methods for medical reasons. CONCLUSION: There was no religious/cultural opposition to the use of SDM. Spousal involvement in use within localities where hormonal methods are not accepted was perceived as an important factor in making the method acceptable. It is imperative to scale up the intervention to other areas both in Nigeria and in other countries that have similar religious and cultural resistance to modern FP methods. PMID- 22092329 TI - Help-seeking behaviours in childbearing women in Ghana, West Africa. AB - AIM: The purpose of this ethnographic study was to examine the health-seeking behaviours of Ghanaian childbearing women. BACKGROUND: The Ashanti consider pregnancy to be a vulnerable time when risk increases that women may be affected by witchcraft and develop sunsumyare. Preparation for positive birth outcomes include biomedical, ethnomedical and faith-based interventions. DESIGN: A sample of 42 childbearing Ghanaian women participated in audiotaped interviews. Transcribed interviews were coded and categorized into themes. FINDINGS AND DISCUSSION: The overriding theme was health seeking to ensure positive pregnancy outcomes. Subthemes included accessing multiple sources of care simultaneously, feeling vulnerable to spiritual illness, seeking spiritual protection and disclosing multiple sources of care. CONCLUSION: Childbearing is an essential part of the gender identity of Ashanti women. Witchcraft mentality provides a way for a woman to manage her life challenges. IMPLICATIONS FOR PRACTICE: Cultural beliefs and practices have profound effects on health-seeking behaviours. It is becoming increasingly important that healthcare providers perform cultural and spiritual assessments and inquire about complementary sources of health care. PMID- 22092330 TI - Factors influencing midwifery migration from the United Kingdom to Australia. AB - BACKGROUND: Within the current literature on the globalization of the healthcare workforce, it is difficult to separate the migration experience of nurses from that of midwives. As more countries are moving to offer direct entry educational programmes and provide separate registration for midwives, information specific to that professional group will be required to guide workforce planners and inform employment practice. This qualitative study tracks the migration experience of midwives moving between the UK and Australia. METHODS: A purposeful sample of 18 midwives who had migrated from the UK to one state in Australia was interviewed within a descriptive phenomenological framework. Data were analysed using thematic coding within Nvivo (QSR International, Melbourne, Australia). RESULTS: The strongest motivator for migration was to improve the family's lifestyle. Push factors included disillusionment with working conditions, standard of living in the UK and national politics. The majority of midwives had organized their own entry visa and employment. Most midwives had occupied senior positions in the UK but accepted employment initially within entry-level positions in Australia. DISCUSSION: Despite both countries offering similar standards of living, the majority of midwives expected to achieve an improvement in family lifestyle in Australia. Midwives indicated they were prepared to lose professional status and seniority of position to gain a better overall lifestyle for their family. To examine the long-term sustainability of international recruitment processes, further research is indicated to examine the ongoing experience and integration of migrant midwives into the workforce in Australia. PMID- 22092331 TI - Nurse teachers' working lives: a questionnaire survey of nursing schools in Mainland China. AB - AIM: The study aimed to explore Chinese nurse teachers' views and experience regarding different components of their working lives. METHODS: A cross-sectional survey of 18 schools of nursing offering nationally accredited baccalaureate nursing programmes across Mainland China was conducted. A total of 227 nurse teachers completed questionnaires yielding a response rate of 72%. FINDINGS: The sample comprised mainly female, married lecturers younger than 44 years with an average teaching experience of about 10 years. The respondents were satisfied with their overall job, work, supervision and co-workers, but dissatisfied with their pay and promotion opportunities. There were statistically significant differences in several facets of job satisfaction across the respondents of different age groups, education levels, job titles and those working in the schools of different sizes. The respondents perceived their work environment to be only somewhat empowering. Their average level of professional identification was relatively high, but their overall role conflict, role ambiguity and sense of coherence were relatively low. CONCLUSION: Chinese nurse teachers had a positive feeling towards their working lives, but strategies should be developed to enhance their sense of coherence and professional commitment. It is worth noting that there is still much adjustment to be made towards the new higher education roles, but the findings may only be generalizable to similar settings. PMID- 22092334 TI - Physical activity is inversely associated with high blood pressure independently of overweight in Brazilian adolescents. AB - The purpose of this study was to assess the relationship between blood pressure (BP) levels and physical activity (PA) domains accounting for overweight/obesity. Adolescents aged 10 to 17 years old were recruited (n = 1021). International Obesity Task Force (IOTF) criteria were used to define overweight and obesity. High BP was defined using the Center of Disease Control and Prevention criteria. Different domains of PA (school activities, sport out of school, and leisure time PA) were assessed using a validated questionnaire. The prevalence of overweight/obesity was 21.9% for boys and 14.8% for girls. Some 13.4% of boys and 10.2% of girls, respectively, had high blood pressure (HBP). A strong and positive association was found between overweight and HBP. After adjustment for body mass index (BMI), total PA was inversely associated with BP. When all PA domains were entered simultaneously in a regression model, and after adjustment for BMI, only sport out of school was significantly and inversely associated with systolic BP [beta: -0.82 (-1.50; -0.13)]. These findings open avenue for the early prevention of HBP by the prevention of obesity and promotion of PA. PMID- 22092333 TI - Hybrid carbon-based scaffolds for applications in soft tissue reconstruction. AB - Current biomedical scaffolds utilized in surgery to repair soft tissues commonly fail to meet the optimal combination of biomechanical and tissue regenerative properties. Carbon is a scaffold alternative that potentially optimizes the balance between mechanical strength, durability, and function as a cell and biologics delivery vehicle that is necessary to restore tissue function while promoting tissue repair. The goals of this study were to investigate the feasibility of fabricating hybrid fibrous carbon scaffolds modified with biopolymer, polycaprolactone and to analyze their mechanical properties and ability to support cell growth and proliferation. Environmental scanning electron microscopy, micro-computed tomography, and cell adhesion and cell proliferation studies were utilized to test scaffold suitability as a cell delivery vehicle. Mechanical properties were tested to examine load failure and elastic modulus. Results were compared to an acellular dermal matrix scaffold control (GraftJacket((r)) [GJ] Matrix), selected for its common use in surgery for the repair of soft tissues. Results indicated that carbon scaffolds exhibited similar mechanical maximums and capacity to support fibroblast adhesion and proliferation in comparison with GJ. Fibroblast adhesion and proliferation was collinear with carbon fiber orientation in regions of sparsely distributed fibers and occurred in clusters in regions of higher fiber density and low porosity. Overall, fibroblast adhesion and proliferation was greatest in lower porosity carbon scaffolds with highly aligned fibers. Stepwise multivariate regression showed that the variability in maximum load of carbon scaffolds and controls were dependent on unique and separate sets of parameters. These finding suggested that there were significant differences in the functional implications of scaffold design and material properties between carbon and dermis derived scaffolds that affect scaffold utility as a tissue replacement construct. PMID- 22092335 TI - Interannual dynamics of viriobenthos abundance and morphological diversity in Chesapeake Bay sediments. AB - Despite significant implications of viral activity in sediment ecosystems, there are limited data describing how sediment viral assemblages respond to broader ecosystem changes. To document this, the spatial and temporal dynamics of viral and bacterial abundance (BA) and changes in the morphological distribution of viruses were examined within three salinity regions over 2 years. Viral abundances (VA) ranged from 0.2 to 17 * 10(10) viruses mL(-1) sediment while direct bacterial counts ranged from 3.8 to 37 * 10(8) cells mL(-1) sediment. Peaks and valleys in the abundance of extracted viruses and bacteria from surface sediments occurred simultaneously, with lows in February 2004 and highs in April 2003. Across all samples, viral and BA were positively correlated (P < 0.001). Vertical profiles showed a decrease in viral and BA with depth in sediments. Based on transmission electron microscopy results, viruses with diminutive capsids (20-50 nm) and from the Myoviridae and Podoviridae viral family types were dominant within surface sediments. The most morphologically diverse viral assemblages occurred in autumn samples from the sandy, polyhaline station and spring samples from the mesohaline station. Seasonal changes showed an average 72% decrease in VA from spring to winter. These observations support the view that viriobenthos assemblages are responsive to seasonal environmental changes and that viral processes have significant implications for the biogeochemical processes mediated by bacterial communities within Bay sediments. PMID- 22092336 TI - Fluorescence imaging with multifunctional polyglycerol sulfates: novel polymeric near-IR probes targeting inflammation. AB - We present a highly selective approach for the targeting of inflammation with a multivalent polymeric probe. Dendritic polyglycerol was employed to synthesize a polyanionic macromolecular conjugate with a near-infrared fluorescent dye related to Indocyanine Green (ICG). On the basis of the dense assembly of sulfate groups which were generated from the polyol core, the resulting polyglycerol sulfate (molecular weight 12 kD with ~70 sulfate groups) targets factors of inflammation (IC(50) of 3-6 nM for inhibition of L-selectin binding) and is specifically transported into inflammatory cells. The in vivo accumulation studied by near-IR fluorescence imaging in an animal model of rheumatoid arthritis demonstrated fast and selective uptake which enabled the differentiation of diseased joints (score 1-3) with a 3.5-fold higher fluorescence level and a signal maximum at 60 min post injection. Localization in tissues using fluorescence histology showed that the conjugates are deposited in the inflammatory infiltrate in the synovial membrane, whereas nonsulfated control was not detected in association with disease. Hence, this type of polymeric imaging probe is an alternative to current bioconjugates and provides future options for targeted imaging and drug delivery. PMID- 22092338 TI - Cutaneous myxoid solitary fibrous tumour. PMID- 22092337 TI - Mechanosensation and maximum bite force in edentulous patients rehabilitated with bimaxillary implant-supported fixed dental prostheses. AB - OBJECTIVE: The aim of this study was to compare tactile sensitivity and maximum voluntary bite force (MBF) of edentulous patients with implant-supported fixed dental prostheses (IFDP/IFDPs) to those wearing complete dentures (CG-CC) and fully dentate subjects (CG-DD). METHODS: Seven edentulous subjects with IFDP/IFDPs, seven with CG-CC and seven CG-DD, matched for age and gender, participated in the pilot experiments. Three active tactile thresholds (absolute, 50% and 100%) were evaluated by means of copper foils of decreasing thickness (12 foils: 700-5 MUm). The passive thresholds were measured in six different sites per quadrant using a custom-made computer-supported strain gauge. MBF was evaluated electronically using the central-bearing point method. RESULTS: Active tactile thresholds were different between all three groups of dental state (Kruskal-Wallis: absolute P = 0.0156; 50% P = 0.0019; 100% P = 0.0059). The active tactile sensitivity with IFDP/IFDPs was between those of the two other groups, except for the 100% threshold. The median passive tactile threshold was higher in patients with IFDP/IFDPs (5.7 N) than in CG-CC (1.7 N) and CG-DD (0.5 N) (Kruskal-Wallis P < 0.0005). MBF did not differ significantly between the dental states (ns). CONCLUSION: IFDP/IFDPs are a valuable treatment option for restoring edentulous patients. Limitations concerning their physiological integration into the orofacial system are mainly related to a poor passive rather than active tactile sensitivity or maximum bite force. PMID- 22092339 TI - Clinical and microbiological characteristics of peri-implantitis cases: a retrospective multicentre study. AB - OBJECTIVES: The aim of this study was to follow patient cases retrospectively in a longitudinal manner from the time of implant placement to the time they were diagnosed with peri-implant disease, and to identify associated clinical and microbiological features of peri-implant disease. MATERIAL AND METHODS: A total of 281 patient cases were chosen from the archives of the Oral Microbiological Diagnostic Laboratory, Gothenburg, Sweden, based on bacterial samples taken from diseased implants. A form was designed and filled in separately for each case including data on patient, implant and disease profile. RESULTS: Most cases were severe peri-implantitis cases (91.4%). In 41.3% of the patients, peri-implantitis was developed early, already after having implants in function less than 4 years. The type of implant surface was significantly associated with the time in years implants were in function, before disease was developed (P < 0.05). The microbiological results by both culture and checkerboard analysis, although failed to fully correspond to the severity of the disease in terms of magnitude, proved to show that peri-implantitis is a polymicrobial anaerobic infection with increased number of AGNB (aerobic Gram-negative bacilli) in 18.6% of the patients. CONCLUSIONS: Peri-implantitis is a biological complication of implants in function that poses a threat to their long-term survival. It may develop earlier around implants with rough surfaces and it may represent a true infection. Microbiological sampling methods should be improved and uniformed so as to fully unveil the microbiological profile of the disease. PMID- 22092340 TI - Roles of siderophore in manganese-oxide reduction by Shewanella oneidensis MR-1. AB - Dissimilatory metal-reducing bacteria (DMRB), such as Shewanella oneidensis MR-1, are of great interest for their importance in the biogeochemical cycling of metals and utility in biotechnological processes, such as bioremediation and microbial fuel cells. To identify genes necessary for metal reduction, this study constructed a random transposon-insertion mutant library of MR-1 and screened it for isolating mutants that were deficient in metal reduction. Examination of approximately 5000 mutants on lactate minimal-medium plates containing MnO(2) resulted in the isolation of one mutant, strain N22-7, that showed a decreased MnO(2)-reduction activity. Determination of a transposon-insertion site in N22-7 followed by deletion and complementation experiments revealed that the disruption of SO3030, a siderophore biosynthesis gene, was responsible for the decreased MnO(2)-reduction activity. In DeltaSO3030 cells, iron and cytochrome contents were decreased to approximately 50% of those in the wild-type cells, when they were incubated under MnO(2)-reduction conditions. In addition, the transcription of genes encoding outer-membrane cytochromes necessary for metal reduction was repressed in DeltaSO3030 under MnO(2)-reduction conditions, while their transcription was upregulated after supplementation of culture media with ferrous iron. These results suggest that siderophore is important for S. oneidensis MR-1 to respire MnO(2), because iron availability influences the expression of cytochromes necessary for metal reduction. PMID- 22092341 TI - Osseointegration of dental implants installed without mechanical engagement: a histometric analysis in dogs. AB - OBJECTIVES: The purpose of this study was to elucidate the healing pattern of sand-blasted, large grid, acid-etched (SLA)-surfaced implants at two healing periods in a model that represents loosened implants (LIs) installed without mechanical engagement. MATERIAL AND METHODS: Five mongrel dogs were used, in which 20 dental implants were prepared. The implants were divided into two groups according to the absence or presence of initial mechanical engagement: LIs) and control, respectively. An oversized drill was used to prepare the implant area for the LI group. The implants were allowed to heal for 4 or 8 weeks. After the healing period, the experimental animals were sacrificed and block sections were obtained for histological analysis and histometric measurements. RESULTS: All implants were in intimate contact with the host bone and were without any inflammation after both 4 and 8 weeks of healing. While the mean amount of bone to-implant contact (BIC) was constant in the control group, it tended to increase in the LI group with increasing healing period. However, neither BIC nor bone density differed significantly between the groups or with the healing period. CONCLUSION: From the results of the study, it can be conjectured that the submerged and unloaded SLA-surfaced implants could result in successful osseointegration, even if the mechanical engagement was not obtained at placement of the implants. PMID- 22092342 TI - Accuracy of data entry of patient race/ethnicity/ancestry and preferred spoken language in an ambulatory care setting. AB - OBJECTIVE: To describe data collection methods and to audit staff data entry of patient self-reported race/ethnicity/ancestry and preferred spoken language (R/E/A/L) information. DATA SOURCE/STUDY SETTING: Large mixed payer outpatient health care organization in Northern California, June 2009. STUDY DESIGN: Secondary analysis of an audit planned and executed by the Department of Clinical Services. DATA COLLECTION/EXTRACTION METHODS: We analyzed concordance between patient written responses and staff data entry. PRINCIPAL FINDINGS: The data entry accuracy rate across questions was high, ranging from 92 to 97 percent. Inaccuracies were due to human error (62 percent), flaws in system design (2 percent), or some combination of both (35 percent). CONCLUSIONS: This study highlights the high accuracy of patient self-reported R/E/A/L data entry and identifies some areas for improvement in staff training and technical system design to facilitate further progress. PMID- 22092343 TI - Noninvasive biosensor for cathepsin L in the stratum corneum. AB - PURPOSE: The objective is to propose an on-site testing biosensor of cathepsin L (CatL) activity in the stratum corneum, which can be used for the evaluation of skin conditions noninvasively and easily. METHODS: The biosensor comprises of a disposable test strip and a desktop-sized reader (260 * 150 * 290 mm(3), 1.9 kg), incorporating a charge-coupled device image sensor (CCD) unit to measure the reflectance of the test strip. A novel immuno-chromatographic test strip was proposed for CatL analysis in the stratum corneum. In order to realize the test strip, a colloidal gold technique was selected as the molecular recognition method for the CatL. A human skin sample was collected noninvasively by adhesive tape stripping. RESULTS: Based on optimal assay conditions, the sensitivity of the biosensor was evaluated. It required 10 min from a sample dropping to appear the test line on the test strip. The optical density was proportion to the CatL. Bioanalytical validation indicated that, within the biosensor's detection limit (172.2 MUU/mL), its accuracy (R(2) = 0.94), and precision (CV = 15%) approach more elaborate laboratory-based analyzers. In addition, the truncated sampling reporting cycle (<15 min) allows speedy reporting of CatL levels. CONCLUSION: It was indicated that this noninvasive and easy-to use biosensor might be a novel tool for the semi-quantitative analysis of CatL in the stratum corneum. PMID- 22092344 TI - Teratoma composed of struma and seminoma arising from an undescended testis. PMID- 22092345 TI - Osseointegration--communication of cells. AB - BACKGROUND: The article provides the scientific documentation for the 3D animated film - "Osseointegration - Communication of cells". AIM: The aim of this article and of the film is to visualise the molecular and cellular events during the healing of an osseous wound after installation of a dental implant with special emphasis on the process of osseointegration. MATERIAL AND RESULTS: In this review article for didactic reasons the concept of the four phases of a healing soft tissue wound was transferred to a bone wound after insertion of a dental implant: haemostasis, inflammatory phase, proliferative phase and remodelling phase. Wound healing throughout these phases is the result of a coordinated action of different cell types which communicate with each other by their interaction using signalling molecules like cytokines, extracellular matrix proteins and small molecules. A regular sequence of cell types controlled by adequate concentrations of signalling molecules results in undisturbed healing. Disturbed healing is associated with a continuation of the early inflammatory phase and the development of a toxic wound environment. The latter is characterized by high counts of polymorphnuclear cells, high concentrations of toxic radicals and proteolytic enzymes and low concentrations of growth factors and extracellular matrix molecules. Clinically the development of a toxic wound environment should be avoided, e.g. by antibacterial measures. DISCUSSION AND CONCLUSION: Experiencing implant osseointegration as a biological process may provide the clinician new targets to improve the therapy with dental implants. PMID- 22092346 TI - Frequencies of blood types A, B, and AB in non-pedigree domestic cats in Beijing. AB - BACKGROUND: Frequencies of blood types A, B, and AB in domestic cats vary geographically and among breeds and have not been reported in China. OBJECTIVE: The purpose of this study was to survey the frequency of blood types in domestic cats in the Beijing area. METHODS: A total of 262 cats from the city of Beijing were blood-typed using a standard tube agglutination assay. All cats were nonpedigree domestic shorthaired and longhaired cats; purebred cats were excluded. Serum obtained from type-B cats and a lectin (Triticum vulgaris) solution served as anti-A and anti-B reagents, respectively. The presence of alloantibodies was also determined in some cats. RESULTS: The frequency of blood types was 88.2% type A, 11.4% type B, and 0.4% type AB. The tube assay resulted in 3+ to 4+ agglutination reactions with either the anti-A or anti-B reagents. The 1 type AB sample showed 3+ agglutination with both anti-A and anti-B reagents; the plasma of that sample did not react with either type-A or type-B RBCs. Tested type-B cats had strong anti-A antibodies. CONCLUSIONS: The frequency of blood type B in the Beijing area was relatively high and similar to that reported for other Asian countries and Australia. Blood-typing is recommended to match donors and recipients before transfusion therapy and planned matings to avoid hemolytic transfusion and neonatal isoerythrolysis reactions, respectively, due to blood-type incompatibility. PMID- 22092347 TI - Segmental Becker's nevi with mucosal involvement. AB - Becker's nevus otherwise known as Becker's pigmented hairy nevus, is a common melanotic epidermal hypermelanosis. It usually presents as a large unilateral patch of hyperpigmentation and hypertrichosis on the shoulder, chest, or back of an adult man. It can be bilateral or multiple and affect areas other than the usual sites. We report a 16-year-old boy with two Becker's nevi on the left side of the face in a segmental distribution with extension onto the oral mucosa. This case is being reported for its rare presentation. PMID- 22092348 TI - Evidence for a curvilinear relationship between sympathetic nervous system activation and women's physiological sexual arousal. AB - There is increasing evidence that women's physiological sexual arousal is facilitated by moderate sympathetic nervous system (SNS) activation. Literature also suggests that the level of SNS activation may play a role in the degree to which SNS activity affects sexual arousal. We provide the first empirical examination of a possible curvilinear relationship between SNS activity and women's genital arousal using a direct measure of SNS activation in 52 sexually functional women. The relationship between heart rate variability (HRV), a specific and sensitive marker of SNS activation, and vaginal pulse amplitude (VPA), a measure of genital arousal, was analyzed. Moderate increases in SNS activity were associated with higher genital arousal, while very low or very high SNS activation was associated with lower genital arousal. These findings imply that there is an optimal level of SNS activation for women's physiological sexual arousal. PMID- 22092349 TI - An evidence-based guideline for unintended pregnancy prevention. AB - Despite the frequency of and significant costs related to unintended pregnancy, it has received less attention in research and prevention guidelines development than other important health threats. This lack of attention has resulted in a system-wide failure to provide care to reproductive aged women who are at risk of unintended pregnancy. An evidence-based blueprint for a coordinated system of primary, secondary, and tertiary prevention is proposed for health professionals who provide care for patients at risk for unintended pregnancy. PMID- 22092350 TI - Metabolic adaptation of human pathogenic and related nonpathogenic bacteria to extra- and intracellular habitats. AB - Most bacteria pathogenic for humans have closely related nonpathogenic counterparts that live as saprophytes, commensals or even symbionts (mutualists) in similar or different habitats. The knowledge of how these bacteria adapt their metabolism to the preferred habitats is critical for our understanding of pathogenesis, commensalism and symbiosis, and - in the case of bacterial pathogens - could help to identify targets for new antimicrobial agents. The focus of this review is on the metabolic potentials and adaptations of three different groups of human extra- and intracellular bacterial pathogens and their nonpathogenic relatives. All bacteria selected have the potential to reach the interior of mammalian host cells. However, their ability to replicate intracellularly differs significantly. The question therefore arises whether there are specific metabolic requirements that support stable intracellular replication. Furthermore, we discuss - whenever relevant data for the pathogenic representatives are available - the possible effect of the metabolism on the expression of virulence genes. PMID- 22092351 TI - Is PPARalpha intron 7 G/C polymorphism associated with muscle strength characteristics in nonathletic young men? AB - Peroxisome proliferator-activated receptor alpha (PPARalpha), a ligand-dependent transcription factor, regulates fatty acid metabolism in heart and skeletal muscle. The intron 7 G/C polymorphism (rs4253778) has been associated with athletic performance. The rare C-allele was predominant in power athletes, whereas the G-allele was more frequent in endurance athletes. In the present study, we investigated the association between this polymorphism and strength characteristics in nonathletic, healthy young adults (n = 500; age 24.2 +/- 4.4 years). Knee torque was measured during concentric knee flexion and extension movements at 60 degrees /s, 120 degrees /s, and 240 degrees /s during 3, 25, and 5 repetitions, respectively. Also, resistance to muscle fatigue (i.e. work last 20% repetitions/work first 20% repetitions *100) was calculated. Differences in knee strength phenotypes between GG homozygous individuals and C-allele carriers were analyzed. The polymorphism did not influence the ability to produce isometric or dynamic knee flexor or extensor peak torque during static or dynamic conditions in this population (0.23 < P < 0.95). Similar results were found for the endurance ratio, a measure for resistance to muscle fatigue. In conclusion, the PPARalpha intron 7 G/C polymorphism does not seem to influence strength characteristics in a nonathletic population. PMID- 22092352 TI - The importance of bicarbonate and nonbicarbonate buffer systems in batch and continuous flow bioreactors for articular cartilage tissue engineering. AB - In cartilage tissue engineering an optimized culture system, maintaining an appropriate extracellular environment (e.g., pH of media), can increase cell proliferation and extracellular matrix (ECM) accumulation. We have previously reported on a continuous-flow bioreactor that improves tissue growth by supplying the cells with a near infinite supply of medium. Previous studies have observed that acidic environments reduce ECM synthesis and chondrocyte proliferation. Hence, in this study we investigated the combined effects of a continuous culture system (bioreactor) together with additional buffering agents (e.g., sodium bicarbonate [NaHCO3]) on cartilaginous tissue growth in vitro. Isolated bovine chondrocytes were grown in three-dimensional cultures, either in static conditions or in a continuous-flow bioreactor, in media with or without NaHCO3. Tissue constructs cultivated in the bioreactor with NaHCO3-supplemented media were characterized with significantly increased (p<0.05) ECM accumulation (glycosaminoglycans a 98-fold increase; collagen a 25-fold increase) and a 13 fold increase in cell proliferation, in comparison with static cultures. Additionally, constructs grown in the bioreactor with NaHCO3-supplemented media were significantly thicker than all other constructs (p<0.05). Further, the chondrocytes from the primary construct expanded and synthesized ECM, forming a secondary construct without a separate expansion phase, with a diameter and thickness of 4 mm and 0.72 mm respectively. Tissue outgrowth was negligible in all other culturing conditions. Thus this study demonstrates the advantage of employing a continuous flow bioreactor coupled with NaHCO3 supplemented media for articular cartilage tissue engineering. PMID- 22092353 TI - Structural and functional changes in the alveolar bone osteoclasts of estrogen treated rats. AB - This study investigated structural and functional features of apoptotic alveolar bone osteoclasts in estrogen-treated rats. For this purpose, 15 female rats 22 days old were divided into three groups: Estrogen (EG), Sham (SG) and Control (CG). The rats of EG received daily intramuscular injection of estrogen for 7 days. The SG received only the oil vehicle. Maxillary fragments containing alveolar bone were removed and processed for light and transmission electron microscopy. Area (OcA) and number of nuclei (OcN) and bone resorption surface per TRAP-positive osteoclasts (BS/OC) were obtained. Vimentin, caspase-3 and MMP-9 immunoreactions, TUNEL/TRAP and MMP-9/TUNEL combined reactions were performed. In EG, the OcA, OcN and BS/Oc were reduced. Moreover, osteoclasts showed cytoplasm immunolabelled by caspase-3 and a different pattern of vimentin expression in comparison with CG and SG. MMP-9 expression was not affected by estrogen and the TUNEL-positive osteoclasts were MMP-9-immunolabelled. In EG, ultrastructural images showed that apoptotic osteoclasts did not exhibit ruffled borders or clear zones and were shedding mononucleated portions. TRAP-positive structures containing irregular and dense chromatin were partially surrounded by fibroblast like cells. In conclusion, the reduction in the BS/Oc may be due to reduction in OcA and OcN; these effects seem to be related to vimentin disarrangement rather than to an interference of estrogen with osteoclast MMP-9 expression. Osteoclast apoptosis involves caspase-3 activity and vimentin degradation; these cells release portions containing one apoptotic nucleus and, subsequently, undergo fragmentation, giving rise to apoptotic bodies. PMID- 22092354 TI - Designing a novel dental root analogue implant using cone beam computed tomography and CAD/CAM technology. AB - OBJECTIVES: The study aim is to introduce a novel preemptively constructed dental root analogue implant (RAI) based on three-dimensional (3D) root surface models obtained from a cone beam computed tomography (CBCT) scan, computer aided designing and computer aided manufacturing technology. MATERIALS & METHODS: One partially edentulous mandibular human cadaver was scanned with the Accuitomo 170 CBCT system. The scan volumes and datasets were used to create 3D surface models of the tooth. A 3D surface mesh of the tooth was stored as a standard triangulation language (STL) file. A high-end selective laser melting technology was used to fabricate the RAI from the STL file. The RAI was produced in a biocompatible titanium alloy (Ti6Al4V). Optical scanning technology was used to measure the RAI, as well as the natural tooth that was extracted. To validate the accuracy of the CBCT 3D root surface and the manufactured Titanium RAI, both surfaces were superimposed on the optical scan of the tooth, which served as the gold "reference" standard. RESULTS: The differences between the RAI and the optical scan of the original tooth are most noticeable at the level of the apex and the cementenamel junction areas on the buccal and lingual side (divergence of more than 0.15 mm). Surface area measurements show an overall decrease in surface area of 6.33% for the RAI in comparison with the original tooth and an increase of 0.27% when comparing the 3D surface model with optical scan of the original tooth. CONCLUSION: With the use of currently available technology it is very well feasible to preemptively create a custom RAI in titanium. However, clinical evidence evaluating the success of this novel dental implant approach is needed. PMID- 22092356 TI - An investigation of the practice activities and coaching behaviors of professional top-level youth soccer coaches. AB - The aim of this study was to investigate the coaching behaviors of elite English youth soccer coaches in different practice settings and gain insight into the coaches' cognitive processes underpinning these behaviors. The practice setting was split into two types of activities, "training form" and "playing form," and behavioral data were collected using a modified version of the Coach Analysis and Intervention System. Interpretive interview data were triangulated with the behavioral data to ensure that both the "what" and the "why" of the coaches' behavior and practice were considered. The results showed the coaches using more "training form" activities than "playing form," and using high levels of prescriptive instruction, regardless of practice type, in contrast to a stated desire to "developing the whole player," creating "decision makers," and being a "facilitator of knowledge creation." The interviews revealed that the coaches had a low self-awareness about their behavior, with an epistemological gap identified between understanding and practice, with statements of intent not being matched by knowledge and action. PMID- 22092355 TI - Assessing factors underlying variation of CO2 emissions in boreal lakes vs. reservoirs. AB - Reservoirs and lakes were compared to test the hypothesis that they are similar with respect to factors driving the variation in CO(2) emissions to the atmosphere. Understanding this variation is necessary for the assessment of the contribution of these freshwater ecosystems to the global carbon cycle. This study, in contrast to previous ones, included analyses of the relationships between CO(2) emissions and microbial communities. Pooled data (lakes and reservoirs) showed that variations in CO(2) emissions were strongly related to variations in temperature, dissolved organic matter (DOM) quality, and bacterial production (BP). Results also showed that lakes were characterized by higher water temperature, lower DOM quality, larger size of Daphnia, and enriched delta(13) C zooplankton compared to reservoirs. Moreover, interactions within plankton communities and relationships between CO(2) emissions and zooplankton delta(13) C signatures differed in lakes vs. reservoirs, indicating among-system type differences in food web structure and carbon cycling. As a result of these ecosystem-type characteristics, CO(2) emission variation was mainly explained by temperature and BP in lakes, and by DOM quality and the ratio of phytoplankton biomass to microheterotroph biomass in reservoirs. These results showed that differences in temperature and DOM quality between lakes and reservoirs translate into differences in microbial interactions and ultimately in the importance of factors driving CO(2) emissions to the atmosphere. They indicated that considering microbial communities and environmental variables such as temperature and DOM quality can help improve our understanding of the variation in CO(2) emissions from freshwater ecosystems. PMID- 22092357 TI - Low-dose transdermal buprenorphine - long-term use and co-medication with other potentially addictive drugs. AB - INTRODUCTION: Recently, low-dose transdermal buprenorphine (LD-TD-BUP) was introduced for treatment of patients with chronic non-malignant pain. The primary aim of this study was to determine the proportion of patients who were prescribed LD-TD-BUP for non-malignant pain who became long-term users. The secondary aim was to determine the proportion of patients who co-medicated with other opioids or benzodiazepines during treatment with LD-TD-BUP. METHODS: Data were drawn from the Norwegian Prescription Database that covers all prescriptions dispensed at pharmacies to the entire Norwegian population (4.7 million inhabitants). The study population consisted of all patients who were dispensed at least one prescription of LD-TD-BUP from its introduction in November 2005 to 31 December 2008. Patients who were dispensed more than 24 patches (>= 6 months) were defined as long-term users. Reimbursement codes were used to stratify patients as having cancer pain or non-malignant pain. RESULTS: Among new users of LD-TD-BUP for non malignant pain (n = 13,451), only 22% became long-term users, while 44% were only dispensed one prescription. Among long-term users who were opioid naive when LD TD-BUP was initiated, 43% co-medicated with other opioids or benzodiazepines, compared with 82% of those who previously had used opioids. CONCLUSION: Three years after introduction, 0.4% of the Norwegian population had been dispensed LD TD-BUP. Only one-fifth had become long-term users. Those who used opioids before the first dispension of LD-TD-BUP co-medicated with other potentially addictive drugs to a much higher degree compared with those who were opioid naive. PMID- 22092358 TI - Comparison of Bacteria and Archaea communities in municipal solid waste, individual refuse components, and leachate. AB - Refuse decomposition in landfills is a microbially mediated process that occurs primarily under anaerobic conditions. Because of limited moisture conditions, hydraulic transport as a means of cellular translocation within the landfill appears limited, especially during the initial stages of decomposition. Thus, microbial communities within the incoming refuse serve as a primary source of facultative and obligate anaerobic microorganisms that initiate refuse decomposition. Fresh residential refuse was collected five times over 26 months, and microbial communities in these samples were compared with those in individual refuse components and decomposed refuse. Bacterial and archaeal community structures were determined using T-RFLP. The Bacterial microbial community richness was correlated (r(2) = 0.91) with seasonal differences in ambient air temperature. Analysis of the results shows that fresh refuse is most likely not the source of methanogens in landfills. Microbial communities in the solid and leachate phases were different, indicating that both matrices must be considered when characterizing microbial diversity within a landfill. PMID- 22092359 TI - The influence of perforating the autogenous block bone and the recipient bed in dogs. Part II: histologic analysis. AB - OBJECTIVES: This study histologically evaluated the influence of cortical perforation of grafted autogenous block bone (ABB) and/or the recipient bed at different healing periods in dogs. MATERIAL AND METHODS: Four ABBs harvested from the posterior mandible were bilaterally fixed onto the maxillary premolar region in five mongrel dogs. The experiments involved four groups according to the perforation site: the ABB and/or the recipient bed. The animals were killed at 1, 4, and 10 days (early healing periods) and 4 and 8 weeks (late healing periods) postoperatively. Specimens were prepared for histological evaluation. RESULTS: In the perforated ABB groups, blood clots had reached the inner surface of the ABB through a surgically prepared pathway, indicating that revascularization had taken place earlier than in the solid ABB groups. Finger-like bony projections into the graft were observed at the interfaces between the ABB and the recipient bed at the fourth week in all four groups. The remodeling process was observed over the entire ABB in the perforated ABB groups, whereas in the solid ABB groups it occurred only at the interface, and the ABB maintained its original lamella structure with more osteoclastic activity. Interestingly, in the perforated ABB groups, additional new bone with a smooth margin was formed above the block bone's original border. CONCLUSION: It was conjectured that intentional cortical perforation of the recipient bed and the ABB might enhance the initial angiogenesis and the integration of the graft. PMID- 22092360 TI - The potential effects of cholecalciferol on bone regeneration in dogs. AB - OBJECTIVES: The aim of this investigation was to evaluate the potential effects of the systemically delivered combination of calcium supplementation and cholecalciferol and of the locally applied biphasic calcium alloplast on the surgically produced alveolar sockets at the early healing stage in a dog model. MATERIALS AND METHODS: The mandibular pre-molars of nine Beagle dogs were extracted first. Three months later, four standardized sockets with a 4 mm in diameter and 6 mm deep cylinder were created bilaterally at healed extraction sites. The sockets on one side were grafted with biphasic calcium phosphate alloplast, whereas the defects on the other side were left un-grafted. The dogs were then randomly divided into two groups; five dogs received oral calcium and cholecalciferol combination (Vit.D/Ca) and were assigned to the test group (Vit.D/Ca Group). The other four dogs without Vit.D/Ca supplement were distributed to the control group (Non-Vit.D/Ca Group). The bone density (Density) and the implant stability quotient (ISQ) at prepared sites were measured 4 weeks later. The drawn bone cores were examined by a histomorphometric analysis for measurement of new bone formation (NBF). The amount of vertical ridge resorption (VRR) was evaluated. RESULTS: The Vit.D/Ca-treated subjects revealed significantly more NBF (P < 0.05), higher bone density (P < 0.05) and significantly less vertical ridge reduction (P < 0.05) in the healing sockets than those without Vit.D/Ca treatment. The non-grafted sockets demonstrated significantly more NBF (P < 0.05), higher bone density (P < 0.05), better ISQ value (P < 0.05) and more vertical ridge reduction (P < 0.05) than those in the grafted sockets. There was no significant difference between the serum data determined before and 4 weeks after experiment in Vit.D/Ca Group or Non-Vit.D/Ca Group. However, the changed value (post-op vs. pre-op) between the two groups was significant in the serum level of phosphate and parathyroid hormone (P = 0.05). CONCLUSION: The results of the present study indicated that the examined calcium phosphate alloplast may perform a function in alveolar ridge preservation while reducing the potential of NBF potential in the healing extraction socket. Also, the combination of calcium supplementation and cholecalciferol may have systemic effects on accelerating bone regeneration. PMID- 22092361 TI - Pseudoepitheliomatous keratotic and micaceous balanitis: comment. PMID- 22092362 TI - A new DNA extraction method by controlled alkaline treatments from consolidated subsurface sediments. AB - Microbial communities that thrive in subterranean consolidated sediments are largely unknown owing to the difficulty of extracting DNA. As this difficulty is often attributed to DNA binding onto the silica-bearing sediment matrix, we developed a DNA extraction method for consolidated sediment from the deep subsurface in which silica minerals were dissolved by being heated under alkaline conditions. NaOH concentrations (0.07 and 0.33 N), incubation temperatures (65 and 94 degrees C) and incubation times (30-90 min) before neutralization were evaluated based on the copy number of extracted prokaryotic DNA. Prokaryotic DNA was detected by quantitative PCR analysis after heating the sediment sample at 94 degrees C in 0.33 N NaOH solution for 50-80 min. Results of 16S rRNA gene sequence analysis of the extracted DNA were all consistent with regard to the dominant occurrence of the metallophilic bacterium, Cupriavidus metallidurans, and Pseudomonas spp. Mineralogical analysis revealed that the dissolution of a silica mineral (opal-CT) during alkaline treatment was maximized at 94 degrees C in 0.33 N NaOH solution for 50 min, which may have resulted in the release of DNA into solution. Because the optimized protocol for DNA extraction is applicable to subterranean consolidated sediments from a different locality, the method developed here has the potential to expand our understanding of the microbial community structure of the deep biosphere. PMID- 22092363 TI - Single-tooth Morse taper connection implants placed in fresh extraction sockets of the anterior maxilla: an aesthetic evaluation. AB - OBJECTIVE: The aim of this retrospective study was to evaluate the aesthetic outcome of single-tooth Morse taper connection implants placed in fresh extraction sockets of the anterior maxilla, by means of the pink aesthetic/white aesthetic score (PES/WES) index. MATERIALS AND METHODS: Twenty-six adult patients (18 men, 8 women, aged between 20 and 62 years; average: 48.7 years) who were treated with an immediate, single-tooth Morse taper connection implant (Leone Implant System(R) , Florence, Italy) in the aesthetic area of the anterior maxilla, were enrolled in this retrospective study. An independent calibrated examiner applied the PES/WES index to 26 single-tooth implant-supported restorations, respectively, 3 months and 2 years after implant placement. RESULTS: No implants were lost. All 26 anterior maxillary single-tooth implants fulfilled the established success criteria for dental implants with regard to osseointegration, including the absence of pain, suppuration, clinically detectable implant mobility, peri-implant radiolucency and prosthetic complications at the implant-abutment interface, with an overall implant-crown success of 100.0%. At the 2-year examination, the mean DIB was 0.44 +/- 0.14 mm (95% CI: 0.41-0.47); the mean total PES/WES was 14.30 +/- 2.78 (range 8-19); the mean PES was 7.30 +/- 1.78 (range 4-10) and the mean WES was 7.00 +/- 1.35 (range 4-10). CONCLUSIONS: The immediate placement of single-tooth Morse taper connection implants in the anterior maxilla seems to represent a successful procedure, from an aesthetic point of view. Further studies are needed to evaluate the aesthetic outcome of single-tooth Morse taper connection implants placed in fresh extraction sockets of the anterior maxilla. PMID- 22092364 TI - Two-dimensional dielectric imaging for dermatologic screening: a feasibility study. AB - BACKGROUND/PURPOSE: The diagnosis of skin neoplasia can be very challenging, given the low sensitivity and specificity of traditional methods of diagnosis which are based on visual appearance. Techniques which are based on the dielectric properties of cells can improve the diagnostic accuracy of screening techniques; as an example, point-contact coaxial probes for dielectric measurement can improve diagnostic accuracy. Unfortunately, these probes are not well suited for two-dimensional spatial imaging of the skin surface, given that they must be manually scanned over the skin surface. METHODS/RESULTS: An electronic scanning probe was developed and fabricated to simulate an open-ended coaxial probe suitable for two-dimensional dielectric imaging of human skin in real time. A clinical study was undertaken to demonstrate proof-of-concept for the instrumentation. A select group of normal healthy subjects as well as a subject with diagnosed squamous cell carcinoma participated in this study. The electronic scanning probe was found to be a potentially useful tool for providing two-dimensional images from diseased skin. CONCLUSION: The electronic scanning probe used for the present study addresses existing limitations with current coaxial probes. Measurements of healthy and diseased areas of skin are provided to illustrate the feasibility of the approach. PMID- 22092365 TI - Lymphopenia in patients with chronic idiopathic neutropenia is associated with decreased number of T-lymphocytes containing T-cell receptor excision circles. AB - OBJECTIVES: Chronic idiopathic neutropenia (CIN) is a disorder of granulopoiesis characterized by the presence of activated T-lymphocytes that induce/sustain apoptosis of bone marrow (BM) granulocytic progenitors. T-cell lymphopenia is commonly found in CIN. The aim of the study is to probe the mechanisms underlying T-cell lymphopenia in CIN. METHODS: We investigated parameters of T-cell homeostasis namely the proliferation/apoptotic rate of naive and memory T cells, the T-cell senescence by telomere measurement, the recent thymic T-cell production through quantification of T-cell receptor rearrangement excision circles (TRECs), and the production of interleukin (IL)-7. RESULTS: Patients with CIN (n = 44) displayed lower proportion of naive CD45RA(+) cells within the CD4(+) and CD8(+) cells compared with controls (n = 15). The proportion of apoptotic cells within the CD8(+) fraction was higher in patients compared with controls and was correlated with the percentage of Ki-67(+) cells, indicating an activation-induced accelerated CD8(+) cell death. The TREC content of CD4(+) and CD8(+) cells was lower in patients compared with controls and was correlated with the proportion of CD45RA(+) CD4(+) and CD8(+) cells and with the levels of serum and BM IL-7, which were significantly decreased in the patients. The mean relative telomere length of CD4(+) and CD8(+) cells was significantly lower in patients with CIN compared with age-matched controls. CONCLUSIONS: The aberrant T cell expansions associated with the pathogenesis of CIN result in increased proliferation/apoptosis and possibly exhaustion of peripheral blood T cells which, in association with the inadequate compensatory thymic export of new TREC expressing T cells partially because of IL-7 deficiency, may contribute to lymphopenia in CIN. PMID- 22092367 TI - Accuracy of professional sports drafts in predicting career potential. AB - The forecasting of talented players is a crucial aspect of building a successful sports franchise and professional sports invest significant resources in making player choices in sport drafts. The current study examined the relationship between career performance (i.e. games played) and draft round for the National Football League, National Hockey League, National Basketball League, and Major League Baseball for players drafted from 1980 to 1989 (n = 4874) against the assumption of a linear relationship between performance and draft round (i.e. that players with the most potential will be selected before players of lower potential). A two-step analysis revealed significant differences in games played across draft rounds (step 1) and a significant negative relationship between draft round and games played (step 2); however, the amount of variance accounted for was relatively low (less than 17%). Results highlight the challenges of accurately evaluating amateur talent. PMID- 22092366 TI - Nursing home price and quality responses to publicly reported quality information. AB - OBJECTIVE: To assess whether the release of Nursing Home Compare (NHC) data affected self-pay per diem prices and quality of care. DATA SOURCES: Primary data sources are the Annual Survey of Wisconsin Nursing Homes for 2001-2003, Online Survey and Certification Reporting System, NHC, and Area Resource File. STUDY DESIGN: We estimated fixed effects models with robust standard errors of per diem self-pay charge and quality before and after NHC. PRINCIPAL FINDINGS: After NHC, low-quality nursing homes raised their prices by a small but significant amount and decreased their use of restraints but did not reduce pressure sores. Mid level and high-quality nursing homes did not significantly increase self-pay prices after NHC nor consistently change quality. CONCLUSIONS: Our findings suggest that the release of quality information affected nursing home behavior, especially pricing and quality decisions among low-quality facilities. Policy makers should continue to monitor quality and prices for self-pay residents and scrutinize low-quality homes over time to see whether they are on a pathway to improve quality. In addition, policy makers should not expect public reporting to result in quick fixes to nursing home quality problems. PMID- 22092368 TI - Response of human bone marrow stromal cells, MG-63, and SaOS-2 to titanium-based dental implant surfaces with different topography and surface energy. AB - OBJECTIVES: Osseointegration is dependent on different parameters of the implant surface like surface roughness and physicochemical properties. In vitro studies using a wide variety of surface parameters and cell lines make it difficult to address the influence of a single parameter. With this study the influence of surface topography and energy on different osteoblast derived cell lines, namely MG-63 and SaOS-2 and of human mesenchymal stromal cells (hMSC) were investigated. MATERIAL AND METHODS: Cells were cultured on polished (POL) and sandblasted/hot acid etched (SBA) titanium surfaces which were partly alkaline treated (SBA NaOH). Cell morphology, metabolic activity, tissue non-specific alkaline phosphatase (TNAP) activity and prostaglandin E(2) (PGE(2) ) formation were determined. RESULTS: Impaired spreading was found on both SBA surfaces. Proliferation after 4 and 7 days increased on POL compared to both SBA surfaces. TNAP activity of hMSC and MG-63 was increased on POL compared to both SBA surfaces whereas SaOS-2 did not discriminate between the three surfaces. PGE(2) formation of hMSC and MG-63 was on both SBA surfaces after 2 days significantly higher than on POL. CONCLUSIONS: The results of this study show that surface roughness has a distinct influence on proliferation and differentiation of osteoblasts. However, variations in physicochemical properties seem to have little influence under the used experimental conditions. It is suggested that more sever and long-lasting modifications of surface chemistry would have an influence on osteoblastic cells. PMID- 22092369 TI - Performance evaluation of the Sysmex pocH-100iV Diff hematology analyzer for analysis of canine, feline, equine, and bovine blood. AB - BACKGROUND: The Sysmex pocH-100iV Diff is an impedance hematology analyzer recently introduced for point-of-care use in veterinary practices in Europe. OBJECTIVE: The purpose of this study was to validate the pocH-100iV Diff for analysis of blood samples from dogs, cats, horses, and cattle. METHODS: Fresh EDTA-blood samples from healthy and ill dogs (115), cats (94), horses (91), and cattle (78) were analyzed on the pocH-100iV Diff and the Cell-Dyn 3500. Results of the automated WBC differential counts were compared with the manual differential counts for 77 dogs, 65 cats, 40 horses, and 46 cattle. HCT were compared with PCVs obtained by microhematocrit centrifugation. Furthermore, precision, linearity, carry-over, cell aging, and clinical relevance of the pocH 100iV Diff results were assessed. RESULTS: Most of the CBC results obtained by the pocH-100iV Diff correlated well with those of the Cell-Dyn 3500. Slightly low correlation was observed for canine MCV and hemoglobin concentration. Lymphocytes correlated well in horses and cattle, but less well in cats and dogs. The mixed cell population termed "OTHRS" (all granulocytes and monocytes for horses and cattle; neutrophils, monocytes, and basophils for cats and dogs) correlated well in all tested species. The instrument overestimated feline and canine eosinophils. In cats, platelet counts showed a strong negative bias. CONCLUSIONS: The overall performance of the pocH-100iV Diff was excellent with the noted limitations. The automated differential count can be used as screening tool in conjunction with evaluation of a blood smear. PMID- 22092370 TI - Melanotic neuroectodermal tumor of infancy. AB - Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon lesion with remarkably consistent histopathologic features that arises primarily in the pediatric population. We describe a MNTI arising in the anterior maxilla of a 6 month-old boy. PMID- 22092371 TI - Editorial Comment to Active surveillance criteria for prostate cancer: can they be applied to Japanese patients? PMID- 22092372 TI - Pathogenesis in tuberculosis: transcriptomic approaches to unraveling virulence mechanisms and finding new drug targets. AB - Tuberculosis (TB) remains a major health problem worldwide. Attempts to control this disease have proved difficult owing to our poor understanding of the pathobiology of Mycobacterium tuberculosis and the emergence of strains that are resistant to multiple drugs currently available for treatment. Genome-wide expression profiling has provided new insight into the transcriptome signatures of the bacterium during infection, notably of macrophages and dendritic cells. These data indicate that M. tuberculosis expresses numerous genes to evade the host immune responses, to suit its intracellular life style, and to respond to various antibiotic drugs. Among the intracellularly induced genes, several have functions in lipid metabolism, cell wall synthesis, iron uptake, oxidative stress resistance, protein secretion, or inhibition of apoptosis. Herein we review these findings and discuss possible ways to exploit the data to understand the complex etiology of TB and to find new effective drug targets. PMID- 22092373 TI - Social cognitive and clinical factors associated with HPV vaccine initiation among urban, economically disadvantaged women. AB - OBJECTIVE: To learn more about human papilloma virus (HPV) knowledge and vaccination among teens and young women age 13 to 26 years from an economically disadvantaged, urban community. Our aim was to identify common beliefs about HPV vaccine initiation and describe the relationship between attitudes, norms, perceived control, and intention to receive HPV vaccine, drawing from the theory of planned behavior (TPB). DESIGN: Mixed method, descriptive design. Guided by the TPB, HPV vaccine beliefs were assessed through focus groups. Intention to receive the vaccine, demographic and clinical factors, and theoretical predictor variables (attitudes, norms, and control) were assessed through questionnaires. SETTING: After recruitment, focus groups were held at a convenient date and time for our participants in a small university conference room. PARTICIPANTS: Participants were economically disadvantaged young women, age 13 to 26 (N = 34). METHODS: Specific behavioral, normative, and control beliefs were elicited in focus groups and analyzed using content analysis. Simple and multivariate general linear modeling with adjustment for prognostic demographic and clinical factors was completed to assess the influence of the theoretical predictor variables on the outcome of HPV vaccine initiation. RESULTS: Influential beliefs toward vaccination were identified. Analysis indicated attitudes, norms, and perceived control toward HPV vaccine initiation were highly significant predictors of intent, as was tobacco use; all p's < .001. CONCLUSION: Barriers to HPV vaccine initiation were identified, and strong preliminary evidence supports use of the TPB to guide programs to promote urban, economically disadvantaged young women's intent to begin the HPV vaccine. PMID- 22092374 TI - Defined electrical stimulation emphasizing excitability for the development and testing of engineered skeletal muscle. AB - Electrical stimulation is required for the maturation of skeletal muscle and as a way to nondestructively monitor muscle development. However, the wrong stimulation parameters can result in electrochemical damage that impairs muscle development/regeneration. The goal of the current study was to determine what aspect of an electrical impulse, specifically the pulse amplitude or pulse width, was detrimental to engineered muscle function and subsequently how engineered muscle responded to continuous electrical stimulation for 24 h. Acute stimulation at a pulse amplitude greater than six-times rheobase resulted in a 2.4-fold increase in the half-relaxation time (32.3+/-0.49 ms vs. 77.4+/-4.35 ms; p<0.05) and a 1.59-fold increase in fatigability (38.2%+/-3.61% vs. 60.6%+/-4.52%; p<0.05). No negative effects were observed when the pulse energy was increased by lengthening the pulse width, indicating electrochemical damage was due to electric fields at or above six-times rheobase. Continuous stimulation for 24 h at electric fields greater than 0.5 V/mm consistently resulted in ~2.5-fold increase in force (0.30+/-0.04 kN/m2 vs. 0.67+/-0.06 kN/m2; p<0.05). Forty per cent of this increase in force was dependent on the mammalian target of rapamycin (RAP) complex 1 (mTORC1), as RAP prevented this portion of the increase in force (CON=0.30+/-0.04 kN/m2 to 0.67+/-0.06 kN/m2 compared with RAP=0.21+/-0.01 kN/m2 to 0.37+/-0.04 kN/m2; p<0.05). Since there was no increase in myosin heavy chain, the remaining increase in force over the 24 h of stimulation is likely due to cytoskeletal rearrangement. These data indicate that electrochemical damage occurs in muscle at a voltage field greater than six-times rheobase and therefore optimal muscle stimulation should be performed using lower electric fields (two- to four-times rheobase). PMID- 22092375 TI - The effect of surrounding conditions on pixel value of cone beam computed tomography. AB - OBJECTIVE: The purpose of this study was to evaluate the reliability of pixel value in CBCT, especially with regard to the effect of surrounding objects that are presented outside the field of view (FOV). MATERIALS AND METHODS: This experiment used the GE Hi-Speed QXi, a multidetector helical computed tomography (MDCT) scanner, and the 3D Accuitomo FPD 8, a cone beam computed tomography (CBCT) scanner. Two types of phantoms were used, both of which contained Lipiodol Ultra Fluid (Lipiodol UF). The type A phantom was a target phantom for pixel value measurement while type B was used for the surrounding environment. For CBCT, the type A phantom was placed in a water bath, and 4 types of surrounding environmental conditions were created: (1) no other phantom present, (2) phantom type B also within the FOV, (3) half of phantom type B within the FOV, (4) phantom type B entirely outside the FOV but within the path of x-rays aimed at phantom A. RESULTS: In MDCT, pixel value (CT number) showed an almost linear correlation with the concentration of Lipiodol UF. In CBCT, on the other hand, pixel value was not linearly correlated with Lipiodol UF concentration. The position of the type B phantom affected pixel values in images of the type A phantom. CONCLUSIONS: Pixel value in CBCT may be affected by various conditions such as beam hardening and surrounding materials, and is therefore not reliable. Caution is essential when pixel values in CBCT are used to estimate bone density at potential implant sites. PMID- 22092376 TI - Selective down-regulation of Th2 cell-mediated airway inflammation in mice by pharmacological intervention of CCR4. AB - BACKGROUND: The chemokine receptor CCR4 has been implicated in Th2 cell-mediated immune responses. However, other T cell subsets are also known to participate in allergic inflammation. OBJECTIVE: The role of CCR4 in Th1, Th2, and Th17 cell mediated allergic airway inflammation was investigated. METHOD: We generated an allergic airway inflammation model by adoptive transfer of in vitro-polarized ovalbumin (OVA)-specific Th1, Th2, and Th17 cells. The effect of a low-molecular weight CCR4 antagonist, Compound 22, on this model was examined. RESULTS: Upon in vitro polarization of DO11.10 naive T cells, Th1- and Th2-polarized cells dominantly expressed CXCR3 and CCR4, respectively, while Th17-polarized cells expressed CCR6 and CCR4. Intranasal OVA-challenge of mice transferred with each T cell subset induced accumulation of T cells in the lungs. Eosinophils were also massively accumulated in Th2-transferred mice, whereas neutrophils were preferentially recruited in Th1- and Th17-transferred mice. Compound 22, as well as anti-CCL17 or anti-CCL22 antibody selectively suppressed accumulation of Th2 cells and eosinophils in the lungs of Th2-transferred and OVA-challenged mice. Compound 22 also inhibited bronchial hyperresponsiveness but had little effect on goblet cell hyperplasia in Th2-transferred and OVA-challenged mice. CONCLUSIONS AND CLINICAL RELEVANCE: There were notable differences in allergic lung inflammation mediated by different T cell subsets. CCR4 blockage was selectively effective for suppression of Th2-mediated allergic inflammation by blocking infiltration of Th2 cells. PMID- 22092378 TI - The effect of ageing and fitness on thermoregulatory response to high-intensity exercise. AB - There are conflicting reports as to whether ageing causes a decreased thermoregulatory response, or if observed differences in previous studies are related to maximal aerobic capacity or training status. This study hypothesized that thermoregulatory response to severe exercise-heat stress is maintained with ageing when both young and older subjects are well trained. Seven older highly trained (OHT = 51-63 years) cyclists were matched with two groups of young cyclists (19-35 years); one group matched for training status [young highly trained (YHT) participants, n = 7] and another for V O 2 max [young moderately trained (YMT), n = 7]. Each participant exercised at 70% V O 2 max in hot (35 degrees C, 40% relative humidity) and thermoneutral (20 degrees C, 40% relative humidity) conditions for 60 min. Final rectal temperature in the thermoneutral and heat (YHT = 39.13 +/- 0.33 degrees C, YMT = 39.11 +/- 0.38 degrees C, OHT = 39.11 +/- 0.51 degrees C) tests were similar between all three groups. %HR(max) (heat test: YHT = 92.5 +/- 6.0%, YMT = 91.6 +/- 4.4%, OHT = 88.6 +/- 5.1%), skin temperature, and cutaneous vascular conductance during cycling in both environments were similar between groups. Lower sweat loss and evaporative heat loss in the heat test in the OHT and YMT groups when compared with the YHT group reflected lower metabolic heat production. The findings of the present study suggest that thermoregulatory response is maintained with age among highly trained subjects. PMID- 22092377 TI - Comparative histological results of different biomaterials used in sinus augmentation procedures: a human study at 6 months. AB - OBJECTIVES: Various grafts or combination of graft materials have been used in sinus floor augmentations, and human histological reports on their performance are available, although limited in number. Histological analysis of the regenerated tissues will provide useful information regarding the nature and amount of newly formed bone. Aim of the present study was a histological and histomorphometric evaluation, in humans, of specimens retrieved from sinuses augmented with phycogene hydroxyapatite, biphasic calcium phosphate ceramics, calcium carbonate, porcine bone and anorganic bovine bone, after a healing period of 6 months. MATERIALS AND METHODS: A total of 15 patients, undergoing 30 sinus augmentation procedures with five different biomaterials, participated in this study. A total of 82 titanium dental implants were inserted in the augmented sinuses after a healing period of 6 months. A total of 60 bone cores, 2 for each augmented sinus, 12 for every biomaterial, were retrieved and all were stored immediately in 10% buffered formalin and processed to obtain thin ground sections. RESULTS: In all biomaterials, many grafted particles were lined and, sometimes, bridged by newly formed bone. Some biomaterials particles appeared to be partially resorbed and substituted by newly formed bone. Histomorphometry showed that, in all biomaterials, newly formed bone and residual grafted material particles represented about 30%. CONCLUSIONS: Longer term histological and histomorphometric studies will be necessary to understand better the resorption times of all these biomaterials. The high interconnecting microporosity allowed, in all the present biomaterials, the ingrowth of newly formed bone and vessels in the pores of the partially resorbed particles. In conclusion, within the limitations of the present study, the data provided support the fact that all these biomaterials can be used, successfully, in sinus augmentation procedures. PMID- 22092379 TI - Similarity and difference among rainforest fruit-feeding butterfly communities in Central and South America. AB - 1. Documenting species abundance distributions in natural environments is critical to ecology and conservation biology. Tropical forest insect faunas vary in space and time, and these partitions can differ in their contribution to overall species diversity. 2. In the Neotropics, the Central American butterfly fauna is best known in terms of general natural history, but butterfly community diversity is best documented by studies on South American fruit-feeding butterflies. Here, we present the first long-term study of fruit-feeding nymphalid species diversity from Central America and provide a unique comparison between Central and South American butterfly communities. 3. This study used 60 months of sampling among multiple spatial and temporal partitions to assess species diversity in a Costa Rican rainforest butterfly community. Abundance distributions varied significantly at the species and higher taxonomic group levels, and canopy and understorey samples were found to be composed of distinct species assemblages. 4. Strong similarities in patterns of species diversity were found between this study and one from Ecuador; yet, there was an important difference in how species richness was distributed in vertical space. In contrast to the Ecuadorian site, Costa Rica had significantly higher canopy richness and lower understorey richness. 5. This study affirms that long-term sampling is vital to understanding tropical insect species abundance distributions and points to potential differences in vertical structure among Central and South American forest insect communities that need to be explored. PMID- 22092380 TI - Clinical efficacy of a xenogeneic collagen matrix in augmenting keratinized mucosa around implants: a randomized controlled prospective clinical trial. AB - AIM: The aim of this controlled randomized clinical trial was to evaluate the efficacy of a xenogeneic collagen matrix (CM) to augment the keratinized tissue around implants supporting prosthetic restorations at 6 months when compared with the standard treatment, the connective tissue autograft, CTG). MATERIALS AND METHODS: This randomized longitudinal parallel controlled clinical trial studied 24 patients with at least one location with minimal keratinized tissue (<=1 mm). MAIN OUTCOME MEASURE: The 6-month width of keratinized tissue. As secondary outcomes the esthetic outlook, the maintenance of peri-implant mucosal health and the patient morbidity were assessed pre-operatively and 1, 3, and 6 months post operatively. RESULTS: At 6 months, Group CTG attained a mean width of keratinized tissue of 2.75 (1.5) mm, while the corresponding figure in Group CM was 2.8 (0.4) mm, the inter-group differences not being statistically significant. The surgical procedure in both groups did not alter significantly the mucosal health in the affected abutments. There was a similar esthetic result and significant increase in the vestibular depth in both groups as a result of the surgery. In the CM group it changed from 2.2 (3.3) to 5.1 (2.5) mm at 6 months. The patients treated with the CM referred less pain, needed less pain medication, and the surgical time was shorter, although these differences were not statistically significant when compared with the CTG group. CONCLUSIONS: These results prove that this new CM was as effective and predictable as the CTG for attaining a band of keratinized tissue. PMID- 22092382 TI - A novel multiplex PCR/RFLP assay for the identification of Streptococcus bovis/Streptococcus equinus complex members from dairy microbial communities based on the 16S rRNA gene. AB - The Streptococcus bovis/Streptococcus equinus complex (SBSEC) comprises pathogenic species associated with different degrees with human infections but also spontaneously fermented dairy products. We aimed therefore at developing a specific identification assay for the SBSEC targeting the 16S rRNA gene comprising a multiplex PCR followed by a differentiating restriction fragment length polymorphisms (RFLP). The multiplex PCR assay was positively applied on 200 SBSEC isolates including reference strains. The assay did not yield false positive amplifications with strains of closely related bacteria and isolates of non-SBSEC streptococci, lactococci, enterococci, and other genera of dairy origin. The downstream RFLP using MseI and XbaI enabled further discrimination of Streptococcus infantarius/S. bovis (biotype II.1) from Streptococcus gallolyticus (biotype I and II.2)/Streptococcus alactolyticus and S. equinus. Furthermore, the newly developed primers can be used directly for Sanger sequencing. Conclusively, this novel PCR/RFLP assay is applicable in the complex dairy microbial communities and provides an important tool to assess the prevalence of members of the SBSEC in dairy products. PMID- 22092381 TI - Bacterial diversity in three distinct sub-habitats within the pitchers of the northern pitcher plant, Sarracenia purpurea. AB - Pitcher plants have been widely used in ecological studies of food webs; however, their bacterial communities are poorly characterized. Pitchers of Sarracenia purpurea contain several distinct sub-habitats, namely the bottom sediment, the liquid, and the internal pitcher wall. We hypothesized that those three sub habitats within pitcher plants are inhabited by distinct bacterial populations. We used denaturing gradient gel electrophoresis and 16S rRNA gene sequencing to characterize bacterial populations in pitchers from three bogs. DGGE and sequencing revealed that in any given pitcher, the three sub-habitats contain significantly different bacterial populations. However, there was significant variability between bacterial populations inhabiting the same type of habitat in different pitchers, even at the same site. Therefore, no consistent set of bacterial populations was enriched in any of the three sub-habitats. All sub habitats appeared to be dominated by alpha- and betaproteobacteria in differing proportions. In addition, sequences from the Bacteroidetes and Firmicutes were obtained from all three sub-habitats. We conclude that container aquatic habitats such as the pitchers of S. purpurea possess a very high bacterial diversity, with many unique bacterial populations enriched in individual pitchers. Within an individual pitcher, populations of certain bacterial families may be enriched in one of the three studied sub-habitats. PMID- 22092386 TI - Probing fibril dissolution of the repeat domain of a functional amyloid, Pmel17, on the microscopic and residue level. AB - Pmel17 is a human amyloid involved in melanin synthesis. A fragment of Pmel17, the repeat domain (RPT) rich in glutamic acids, forms amyloid only at mildly acidic pH. Unlike pathological amyloids, these fibrils dissolve at neutral pH, supporting a reversible aggregation-disaggregation process. Here, we study RPT dissolution using atomic force microscopy and solution-state nuclear magnetic resonance spectroscopy. Our results reveal asymmetric fibril disassembly proceeding in the absence of intermediates. We suggest that fibril unfolding involves multiple deprotonation events resulting in electrostatic charge repulsion and filament dissolution. PMID- 22092387 TI - Quantitative biomechanical analysis of the influence of the cortical bone and implant length on primary stability. AB - AIM: The aim of the study was to investigate the influence of cortical bone and increasing implant fixture length on primary stability. Further investigation considered the correlation between the presence of cortical bone at the marginal bone and implant stability measured by insertion torque (IT) and resonance frequency analysis (RFA), as well as implant length, were determined. MATERIALS AND METHODS: Two different types of polyurethane bone models were compared. (Group 1: with cortical and cancellous bone; Group 2: with cancellous bone only). A total of 60 external type implants (? 4.1, OSSTEM((r)), US II((r))) with different lengths (7, 10, and 13 mm) were used. IT was recorded automatically by a computer which was connected to the Implant fixture installation device during the placement. RFA was conducted to quantify the primary implant stability quotient (ISQ). All two measurements were repeated 10 times for each group. RESULTS: All these differences were statistically significant between the two groups (P < 0.001) and intragroups (P < 0.001). Upon comparing the IT, cortical bone appears to have a greater influence on implant stability than implant lengths, whereas the RFA value strongly affects implant length rather than the presence of the crestal cortical bone. CONCLUSIONS: The quantitative biomechanical evaluations clearly demonstrated that primary implant stability seems to be influenced by the presence of a cortical plate and total surface area of the implant fixture appears to be the decisive determinant for ISQ value. PMID- 22092388 TI - Application of high-throughput sequencing to measure the performance of commonly used selective cultivation methods for the foodborne pathogen Campylobacter. AB - Campylobacter is an important foodborne human pathogen, which has traditionally been studied using a variety of selective cultivation methods. Here we use next generation sequencing to ask the following: (i) how selective are commonly used Campylobacter cultivation methods relative to the initial sample and (ii) how do the specificity and sensitivity of these methods compare with one another? To answer these questions, we used 16S rRNA tagged-pyrosequencing to sequence directly from a pooled fecal sample representing a c. 16,000 bird poultry flock and compared these data to exhaustive sequencing of colonies formed after plating. We compared five commonly used media [Cefex, Cape Town, modified cefoperazone charcoal deoxycholate agar (mCCDA), Campy-Line agar (CLA), and Campy CVA agar (CVA)], two incubation atmospheres (10% CO(2), 5% O(2), 85% N(2) and 10% CO(2), 10% H(2), 80% N(2)), and two incubation temperatures (37 and 42 degrees C). Analysis of 404,104 total sequence reads, including 19 472 total fecal reads, revealed Campylobacter represented only a small proportion (< 0.04%) of sequences present in the feces, but 88-97% of sequences from each media type. Incubation atmosphere had little effect on recovery, but a significant difference in media specificity (more non-Campylobacter OTUs; P = 0.028) was found at 42 vs. 37 degrees C. The most common non-Campylobacter sequence type was Proteus, which ranged from 0.04% of sequences (mCCDA) to 10.8% (Cape Town). High-throughput sequencing provides a novel and powerful approach to measure the performance of selective media, which remain widely used for research and regulatory purposes. PMID- 22092389 TI - The impact of local anesthetic volume and concentration on pain during prostate biopsy: a prospective randomized trial. AB - PURPOSE: To evaluate the effect of equivalent doses of local anesthetic administered at different concentrations and volumes on pain scores in patients undergoing prostate biopsy. PATIENTS AND METHODS: This study was a single-center, randomized trial. A total of 120 patients were randomized into two groups with 60 patients in each group. In group 1, 2.5 mL of 2% lidocaine (low volume-high concentration) and in group 2, 5 mL of 1% lidocaine (high volume-low concentration) was injected just lateral to the junction between the prostate base and seminal vesicle on each side under ultrasonographic guidance. Patients were given an 11 point visual analog scale (VAS) to evaluate the level of pain encountered during transrectal ultrasonographic (TRUS) probe insertion, injection of the local anesthetic, and the biopsy procedure. RESULTS: In both groups, TRUS probe insertion was the most painful stage of the procedure. With regard to local anesthetic injection, the VAS pain score was significantly lower in group 1 (1.56 vs. 2.41, P=0.001). Concerning sampling of the prostate, group 1 had a significantly lower VAS pain score compared with group 2 (1.71 vs. 2.48, P=0.008). Neither major complications nor side effects related to local anesthetic absorption occurred in both groups. CONCLUSION: Low volume-high concentration lidocaine administration provides superior analgesia compared with high volume-low concentration lidocaine during transrectal biopsy of the prostate. PMID- 22092390 TI - Multiple myeloma vs. breast cancer patients with bisphosphonates-related osteonecrosis of the jaws: a comparative analysis of response to treatment and predictors of outcome. AB - BACKGROUND: Multiple myeloma (MM) and breast cancer (BC) are the two most common diseases associated with bisphosphonates-related osteonecrosis of the jaws (BRONJ), for which different therapeutical approaches have been proposed. The aim of this study was to compare the clinical behaviour of BRONJ in patients with MM vs. BC and the time of healing in terms of clinical and symptomatological remission, following a standardized therapeutic protocol. METHODS: Twenty-six BRONJ patients (13 men with MM and 13 women with BC) were prospectively enroled and treated with a specific systemic and topical antibiotic therapy. Several predictors of outcome were also evaluated. RESULTS: Nine patients (69.2%) with BC and 10 patients (76.9%) with MM progressed towards a complete clinical remission (CR) in a mean healing time of 183.3 days [SD: 113.7; 95% confidence interval (CI): 95.95-207.7] and 372.0 days (SD: 308.0; 95% CI: 151.7-592.3) (P = 0.776), respectively. The clinical improvement was statistically significant (P = 0.0013 and P = 0.0014), as well as the assessment of pain (P = 0.0015 and P = 0.0015), in MM and BC group, respectively. Cox regression analysis revealed that just triggering events (P = 0.036) were found to be significant predictors of outcome of BRONJ healing. CONCLUSIONS: Both groups of cancer patients experienced clinical and symptomatological remission regardless their malignancy, but BC patients earlier than MM patients. PMID- 22092391 TI - Intraosseous transcutaneous amputation prosthesis (ITAP) for limb salvage in 4 dogs. AB - OBJECTIVE: To report clinical application of intraosseous transcutaneous amputation prosthesis (ITAP) for limb salvage. STUDY DESIGN: Retrospective case series. SAMPLE POPULATION: Client owned dogs with malignant neoplasia of the distal aspect of the limb. METHOD: Distal limb amputation allowed press-fit insertion of the ITAP into the radius (n = 3) or tibia (1). Remaining soft tissues including skin were attached directly to the ITAP. Limb stump and ITAP were protected by bandaging (1) or external skeletal fixation (3) for 5-6 weeks before exoprosthesis attachment. Measures of outcome included subjective assessments of limb function by owners and veterinarians, radiographic (4) and histologic (1) examination. RESULTS: Dermal integration with the ITAP was achieved by 3 weeks and dogs were walking in a pain-free manner by 8 weeks. One dog was administered adjunctive carboplatin chemotherapy. No evidence of local tumor recurrence occurred. In 1 dog, ITAP fracture occurred at 10 weeks and was successfully managed by ITAP replacement. Three dogs were euthanatized because of confirmed or assumed metastatic disease at 8, 12, and 17 months. Histologic examination of the ITAP-limb interface at 1 year documented osseous and dermal integration. CONCLUSION: Implantation of ITAP to the distal limb of dogs is feasible and can result in favorable functional outcomes. Biological integration of osseous and dermal tissues with ITAP is reliable and robust. PMID- 22092392 TI - Primary care and health outcomes among older patients with diabetes. AB - OBJECTIVE: The aim of this study was to measure the relationship between days spent waiting for primary care and health outcomes among patients diagnosed with diabetes, especially among the elderly population. DATA SOURCE: Secondary data from VA administrative databases and Medicare claims. STUDY DESIGN: This is a retrospective observational study. Outcome variables include primary care utilization, mortality, heart attack, stroke, and ambulatory-care sensitive condition (ACSC) hospitalization. The main explanatory variable of interest is VA primary care wait time. Negative binomial models predict utilization and stacked logistic regression models predict the probability of experiencing each health outcome. Models are stratified by the presence of a selected health condition and age. PRINCIPAL FINDINGS: Longer wait times were predicted to decrease utilization between 2 and 4 percent. There was no significant relationship between wait times and health outcomes for the overall sample. In stratified analyses, longer waits were associated with undesirable outcomes for those over age 70 with one of the selected health conditions or in certain narrower 5-year age groups, but the overall pattern of results does not indicate a systematic and significant effect. CONCLUSIONS: There was a modest effect of long wait times on primary care utilization but no robust effect of longer wait times on health outcomes. Waiting for care did not significantly compromise long-term health outcomes for veterans with diabetes. PMID- 22092393 TI - Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinoma. AB - AIMS: To determine the extent of HER2 homogeneity/heterogeneity in primary versus metastatic gastric carcinoma (GC). MATERIALS AND RESULTS: The human epidermal growth factor receptor 2 (HER2) status in primary and metastatic lesions was evaluated by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH). Four separate cohorts consisting of primary GC alone or primary GC paired with metastatic lesions were examined. In the FISH analysis of 325 primary GCs, eight cases (2.5%) showed amplification with a heterogeneous pattern, whereas 27 cases (8.3%) showed amplification with a homogeneous pattern, and in this cohort the discordant:concordant FISH ratio based on examination of three different areas in each primary lesion was 0.30:1. FISH testing using 250 paired primary and metastatic lesions revealed seven cases (2.8%) with discordant amplification. In metastatic disease positive conversion occurred in six cases (2.4%), whereas negative conversion happened in one case (0.4%). The discordant:concordant ratio of primary versus secondary lesions was 0.23:1. When the seven discordant cases were re-evaluated using whole sections of primary GCs, six showed a heterogeneous pattern of amplification. CONCLUSIONS: These findings suggest that the discordant HER2 amplification observed in metastatic lesions is explained substantially by heterogeneity within primary tumours. PMID- 22092394 TI - Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections. AB - AIMS: To assess human epidermal growth factor receptor 2 (HER2) status and heterogeneity using immunohistochemistry (IHC) and silver in-situ hybridization (SISH) in gastric carcinoma and dysplasia, and to correlate HER2 status between biopsy and resection specimens of gastric carcinoma. METHODS AND RESULTS: Immunohistochemistry for HER2 was performed in 178 cases of gastric carcinoma, and SISH in cases showing at least 1+ reaction. HER2 positivity [European Medicines Agency (EMA) guidelines] was identified in 20.2% of carcinomas and 12.9% of high-grade dysplasia, and HER2 heterogeneity noted in 50% and 33% of these cases, respectively. IHC negative/positive reactivity and SISH results were concordant in 96.2%. SISH amplification was seen in 35.3% of IHC 2+ and in a case with previously unrecognized staining pattern. Concordance of IHC HER2 status on biopsies and gastrectomies was seen in 74.1%. False negative IHC results on either the biopsy or gastrectomy were seen in 19.4% of HER2 amplified cases. CONCLUSIONS: Human epidermal growth factor receptor 2 status in gastric carcinoma is comparable to previous studies with good concordance between IHC and SISH; all IHC 2+ and unusual patterns should be assessed with ISH studies; heterogeneity of tumour HER2 overexpression/amplification is common with possible implications for HER2 testing; and HER2 overexpression appears sufficiently specific to be considered a potential diagnostic biomarker of dysplasia. PMID- 22092395 TI - Nuclear atypia grading score is a useful prognostic factor in papillary gastric adenocarcinoma. AB - AIMS: To investigate nuclear atypical in papillary gastric adenocarcinoma (PGA). METHOD AND RESULTS: Hundred cases of PGA were classified into two groups according to nuclear pleomorphism and nuclear polarity; these groups were designated as high nuclear grade and low nuclear grade. Correlations between nuclear grade and clinicopathological features were evaluated for prognostic value. In order to evaluate which types of biological factors influence nuclear atypia, the expression of gastric-type mucin phenotype, p53, HER2 and Ki-67 detected by immunohistochemistry and DNA ploidy detected by laser scanning cytometry. The high nuclear grade group correlated with deeper wall invasion, the presence of lymphatic and venous invasion and the positivity of lymph node metastasis. High nuclear grade was an independent prognostic factor for disease free survival. Moreover, significant correlations were observed between high nuclear grade and positivity of gastric-type mucin phenotype, p53 and HER2 and DNA aneuploidy. CONCLUSION: Nuclear grade could be a new and useful morphological predictor for high malignant potential in PGA. PMID- 22092396 TI - Focal active colitis: a prospective study of clinicopathological correlations in 90 patients. AB - AIMS: Considerable controversy exists about the clinical implication of a diagnosis of focal active colitis (FAC). The aim of this study was to assess clinicopathological correlations of FAC in 90 adults, representing the largest and only prospective series of FAC. METHODS AND RESULTS: Patients were assessed by comprehensive clinical follow-up and questionnaires. Fifteen histopathological features were scored and correlated with clinical outcome. In 24% of patients drugs, especially NSAIDs, were implicated. Infection was a probable cause in 19%. In 14 patients (15.6%), predominantly women, a diagnosis of chronic inflammatory bowel disease was ultimately made. Most were Crohn's disease, but this is the first study in which FAC has presaged an ultimate diagnosis of ulcerative colitis in adults (in two patients). A specific subtype of FAC, termed basal FAC, was significantly associated with drugs. These excepted, this study has found no histopathological parameters of FAC, such as amount, location and/or distribution, to correlate with clinical outcome or allowed selection of those patients more likely to show subsequent evidence of chronic inflammatory bowel disease. CONCLUSION: This study has provided powerful information on the implication of a diagnosis of FAC. In a small but not inconsiderable case number, the ultimate diagnosis will be chronic inflammatory bowel disease. PMID- 22092397 TI - Aggressive colorectal carcinoma phenotypes of invasion can be assessed reproducibly and effectively predict poor survival: interobserver study and multivariate survival analysis of a prospectively collected series of 299 patients after potentially curative resections with long-term follow-up. AB - AIMS: To test whether assessment of colorectal carcinoma phenotypes of invasion can be taught successfully to pathologists not familiar with these features and to confirm their prognostic impact. METHODS AND RESULTS: A junior member of staff was supplied with written information and a generous set of images on how to type the invasive margin of colorectal carcinomas (expansive versus infiltrative) and how to assess tumour budding (counting on pan-cytokeratin immunostains; cut-off at the 66th percentile). An interobserver study yielded kappa values of 0.578 and 0.438 for typing the invasive margin and assessment of tumour budding, respectively. Margin typing improved significantly to kappa=0.939 after a training session. However, using a cut-off, assessment of tumour budding improved only moderately to kappa=0.629 although, numerically, divergences were within +/ 10%. On univariate analysis, a high-degree of tumour budding and the infiltrative type of invasive margin were strong negative prognostic factors. The Cox model included nodal status, tumour budding, serosal penetration and venous angioinvasion. Importantly, using the tumour budding counts as a numerical variable for the Cox model also yielded significant odds, allowing the constraints of a cut-off to be relinquished. CONCLUSIONS: Assessment of colorectal carcinoma phenotypes of invasion can be learnt and performed with confidence, and their prognostic impact is confirmed in this independent series. PMID- 22092398 TI - Histological and immunohistological findings in biliary intraepithelial neoplasia arising from a background of chronic biliary disease compared with liver cirrhosis of non-biliary aetiology. AB - AIMS: Hitherto, biliary intraepithelial neoplasia (BilIN) has been described in chronic biliary disease but rarely in non-biliary liver cirrhosis (LC). Intraepithelial neoplasia of the pancreas shows alterations in the expression of cell cycle and mucin core proteins. The aim of this study was to evaluate BilIN and reactive biliary lesions in biliary disease and non-biliary LC. METHODS AND RESULTS: BilIN was found in 51% (33 of 65) of liver tissue cases of biliary disease, and in 11% (34 of 310) of the LC group. Immunohistologically, MUC5AC, an 'early phase' protein, and Ki67, reflecting 'late phase' expression, were identified with increasing degrees of dysplasia in both groups, but that expression was significantly higher in the biliary disease group. 'Early phase' cell cycle proteins, p16 (decrease) and p21 (increase) altered in both biliary and LC groups with increasing degrees of dysplasia. CONCLUSIONS: We found BilIN in the large bile ducts of hepatitis B virus- and hepatitis C virus-related LC as well as in cases related to a biliary aetiology. The LC group was significantly less likely to show changes in the expression of MUC5AC and proliferative activity than the biliary group. Alterations in p16 and p21 reflected increasing degrees of dysplasia in both groups. PMID- 22092399 TI - Pulmonary capillary haemangiomatosis-like lesions in severely congested lungs. AB - AIMS: To elucidate the nature of capillary alterations in the severe form of pulmonary venous congestion (SPVC). METHODS AND RESULTS: Post-mortem lungs from 52 patients with left-sided cardiac failure were examined, including 31 cases of valvular heart disease and 21 cases of cardiomyopathy. Six post-mortem lungs (six of 52, 11.5%) had patchy lesions composed of markedly widened alveolar walls containing numerous dilated capillaries. These features strikingly mimicked pulmonary capillary haemangiomatosis (PCH). Moreover, one (one of 52, 1.9%) lung showed numerous fibrous micronodules containing capillaries with or without ossification, associated with prominent capillary sprouts, suggesting capillary varicose changes. No pathological features suggesting plexiform angiopathy or veno-occlusive disease were found. Ultrastructural examination revealed occasional interposition of swollen endothelial cells in the thickened basement membranes of the pulmonary capillaries. CONCLUSION: PCH-like lesions can occur infrequently as an incidental finding in SPVC, rarely accompanying ossifying fibrocapillary micronodules. These lesions are considered to be a secondary form of PCH, representing severely tortuous and proliferative capillary changes rather than neoplasia. PMID- 22092400 TI - An immunohistochemical analysis-based decision tree model for estimating the risk of lymphatic metastasis in pN0 squamous cell carcinomas of the lung. AB - AIMS: Lung cancer patients within the pN0 category have a significantly different outcome. The aim of this study was to develop a mathematical model to assist in predicting the prognosis of pN0 lung squamous cell carcinoma (SCC). METHODS AND RESULTS: Twenty-three proteins were examined by immunohistochemical (IHC) analysis on primary tumour tissues from 319 lung SCC patients. In a training group, using IHC data, a recursive partitioning decision tree (RP-DT) was used to build a model for estimating the risk for lymphatic metastasis. This model was then validated in a test cohort. Of 23 proteins, 8 (matrix metallopeptidase 1, metalloproteinase inhibitor 1, Ras GTPase-activating-like protein IQGAP1, targeting protein for Xklp2, urokinase-type plasminogen activator, cathepsin D, fascin, polymeric immunoglobulin receptor/secretory component) were selected, and generated a tree model in a training group of 255 patients to classify them as at high or low risk of lymphatic invasion, with accuracy of 78.0% (compared to histopathological diagnosis), sensitivity of 83.0% and specificity of 70.3%. When the tree model was applied to the test group, the accuracy, sensitivity and specificity were 76.6%, 76.0% and 76.9%, respectively. The performance of this mathematical model was substantiated further in 34 'problematic' stage I/pN0 patients by survival analysis. CONCLUSIONS: The RP-DT model, constructed with eight protein markers for estimating lymphatic metastasis risk in pN0 lung SCC, is clinically feasible and practical, using IHC data from the primary tumour. PMID- 22092401 TI - Large needle aspiration biopsy histology for preoperative selection of Hurthle cell thyroid nodules. AB - AIMS: To assess whether the large needle aspiration biopsy (LNAB) histological distinction between pure microfollicular nodules and mixed micro-macrofollicular nodules can assist preoperative selection of a Hurthle cell nodule (HCN) discovered by fine needle aspiration cytology (FNAC). METHODS AND RESULTS: In 24 HCN identified by preoperative FNAC, preoperative LNAB histology was compared with postoperative pathology. FNAC demonstrated seven benign HCN (negative), eight HCN with atypia (positive); seven suspected cancers with HC (positive); and two cancers with Hurthle cells (positive). LNAB showed mixed micro macrofollicular hyperplastic features in 12 nodules (negative) and a microfollicular structure in 12 nodules (positive), two of which included findings of papillary cancer. Postoperative findings were benign (negative) in 16 patients and malignant (positive) in eight patients. The sensitivity and specificity for FNAC were 87.5% [seven of eight, 95% confidence interval (CI): 47.3-99.7%) and 37.5% (six of 16, 95% CI: 15.2-64.6%], respectively, and for LNAB were 87.5% (seven of eight, 95% CI: 47.3-99.7%) and 68.8% (11 of 16, 95% CI: 41.3 89.0%), respectively. FNAC results were significantly different from postoperative results (McNemar's test, exact two-sided P=0.012), while LNAB results were not (McNemar's test, exact two-sided P=0.219). CONCLUSIONS: These data suggest that LNAB histology is more accurate than FNAC cytology for the preoperative selection of HCN. PMID- 22092402 TI - Cytoplasmic expression of oestrogen receptor beta (ERbeta) as a prognostic factor in vulvar squamous cell carcinoma in elderly women. AB - AIMS: To investigate the prognostic value of cytoplasmic oestrogen receptor beta (ERbeta) expression in a series of untreated patients with non-human papillomavirus (HPV)-related vulvar cancer. METHODS AND RESULTS: Immunohistochemistry was carried out using a polyclonal rabbit anti-human ERbeta antibody. The nuclear and cytoplasmic expression of ERbeta was evaluated in 33 patients. Cytoplasmic immunoreactivity was correlated with histopathological and molecular parameters (Ki67, p21), disease-free survival (DFS) and overall survival (OS). The expression of cytoplasmic ERbeta was found to be associated with grade (P=0.006), while no association was found with any of the remaining variables examined. Cases with high cytoplasmic ERbeta expression showed lower DFS and OS compared to cases with low cytoplasmic ERbeta (P=0.007, P=0.01, respectively). There was also a progressive decline in both the DFS and OS with increasing tumour size (P=0.05, P=0.07, respectively) and with increasing depth of infiltration (P=0.14, P=0.07, respectively). On multivariate analysis, only tumour size and cytoplasmic ERbeta staining retained an independent negative prognostic role for DFS and OS. CONCLUSIONS: The assessment of cytoplasmic ERbeta expression could be helpful to identify poor prognosis in elderly patients with non-HPV-related vulvar squamous cell carcinoma (SCC). PMID- 22092403 TI - Evaluation of a hormone receptor-positive ovarian carcinoma subtype with a favourable prognosis by determination of progesterone receptor and oestrogen receptor 1 mRNA expression in formalin-fixed paraffin-embedded tissue. AB - AIMS: In vitro and epidemiological studies indicate an essential role for progesterone in the aetiology and progression of ovarian carcinoma. The aim of this study was to examine the prognostic role of progesterone receptor (PR) protein and mRNA expression. METHODS AND RESULTS: PR expression was examined by immunohistochemistry (n=143) and kinetic reverse transcription-polymerase chain reaction (RT-PCR) from formalin-fixed and paraffin-embedded tissue (n=55). PR mRNA and protein expression correlated (P<0.0001). PR mRNA was a positive predictor for overall and progression-free survival (P=0.0005 and P<0.0001, respectively). Protein expression was also prognostic (P=0.015 and P=0.0011, respectively), whereas only PR mRNA retained its prognostic value on multivariate analysis (P=0.04). PR mRNA was still a positive prognostic marker among oestrogen receptor 1 (ESR1) mRNA-positive tumours (P=0.0007) and survival was best in patients with PR- and ESR1-positive phenotypes (P=0.0155 and P=0.0016, respectively). CONCLUSION: Expression of PR and ESR1 defines a subgroup of ovarian carcinomas with a favourable prognosis. PR and ESR1 mRNA expression analysis is a sensitive, quantitative and easy-to-perform high-throughput analytical tool for the identification of this subgroup and could be predictive in clinical trials focused on patients with potential benefit from hormonal treatment. PMID- 22092405 TI - Factors influencing the agreement on histopathological assessments of breast biopsies among pathologists. AB - AIMS: It has been recommended that the histopathology results of core biopsies of the breast are categorized according to the B-categorization scheme. We measured the interobserver variability of the B-categorization of core biopsies of the breast. METHODS AND RESULTS: Core biopsies were taken among 765 women at the University of Halle between 2006 and 2008. All histological slides were reviewed in a blinded fashion by two experienced breast pathologists. We calculated observed and chance-corrected agreements (kappa) and 95% confidence intervals (CI). The prevalence of B3-B5 biopsies was 41.6%. The observed and weighted kappa agreement of the five-level B-categorization scheme was 0.87 (95% CI: 0.84 -0.89) and 0.89 (95% CI: 0.89-0.91), respectively. The most frequent disagreement was between B2 and B3 (47 of 103 disagreements, 45.6%). Overall, 49.5% of all disagreements were clinically relevant disagreements that would imply different therapeutic strategies. Agreement was modified by referral group, Breast Imaging Reporting and Data System (BIRADS) level, radiological breast density, imaging guidance and application of immunohistological staining. CONCLUSIONS: Interobserver agreement of the B-categorization scheme was high and was modified by referral status, level of radiological suspicion of breast cancer, breast density, imaging guidance of core biopsies and requirement of additional immunohistological staining. PMID- 22092404 TI - Unexplained fetal death has a biological signature of maternal anti-fetal rejection: chronic chorioamnionitis and alloimmune anti-human leucocyte antigen antibodies. AB - AIMS: Chronic chorioamnionitis is a histological manifestation of maternal anti fetal cellular rejection. As failure of graft survival is the most catastrophic event in organ transplantation, we hypothesized that fetal death could be a consequence of maternal rejection. The aim of this study was to assess whether there is evidence of cellular and antibody-mediated rejection in fetal death. METHODS AND RESULTS: Placental histology was reviewed for the presence of chronic chorioamnionitis in unexplained preterm fetal death (n=30) and preterm live birth (n=103). Amniotic fluid CXCL10 concentrations were measured with a specific immunoassay. Chronic chorioamnionitis was more frequent in fetal death than in live birth (60.0% versus 37.9%; P<0.05) and fetal death had a higher median amniotic fluid CXCL10 concentration than live birth (2.0 versus 1.8 ng/ml, P<0.05), after adjusting for gestational age at amniocentesis. Maternal anti human leucocyte antigen class II panel-reactive seropositivity determined by flow cytometry was higher in fetal death compared to live birth (35.7% versus 10.9%; P<0.05). CONCLUSIONS: Chronic chorioamnionitis is a common pathologic feature in unexplained preterm fetal death. This novel finding suggests that cellular and antibody-mediated anti-fetal rejection of the mother is associated with fetal death (graft failure) in human pregnancy. PMID- 22092406 TI - Expression of calretinin by breast carcinoma and the potential for misdiagnosis of mesothelioma. AB - AIMS: Calretinin and cytokeratin (CK)5/6 are frequently used to differentiate between metastatic breast cancer and primary malignant mesothelioma in pleural biopsies, but both tumours may express these markers. This study was aimed at evaluating the frequency of calretinin expression in primary breast carcinomas, and assessing the characteristics of the calretinin-positive tumours. METHODS AND RESULTS: Fifty-three primary breast adenocarcinomas were analysed for immunohistochemical expression of calretinin. CK5/6 and epidermal growth factor receptor (EGFR) immunostaining were performed on the calretinin-positive subset. Tumours were classified as basal-like if they met standard morphological and immunohistochemical criteria. Fifteen per cent (8/53) of the breast tumours were positive for calretinin. Eighty-eight per cent (7/8) of the calretinin-positive tumours were grade 3, as compared with 20% (9/45) of the calretinin-negative tumours (P<0.001). Only 13% (1/8) of the calretinin-positive tumours were also oestrogen receptor (ER)-positive, as compared with 87% (39/45) of the calretinin negative tumours (P<0.001). Eleven per cent (6/53) of the tumours were classified as basal-like. Of these, four were positive for calretinin and two were negative (P=0.003). CONCLUSIONS: Fifteen per cent of breast carcinomas stain with calretinin. These tumours are more likely to be high-grade, ER-negative, and display a basal-like phenotype. These tumours may be misdiagnosed as malignant mesothelioma when they metastasize to the pleura. PMID- 22092407 TI - Mesothelial markers in high-grade breast carcinoma. AB - AIMS: Advances in molecular profiling have subdivided breast carcinomas into distinct subtypes. Basal carcinomas are generally oestrogen receptor (ER) progesterone receptor (PR)-/human epidermal growth factor receptor 2 (HER2)-, and cytokeratin (CK)5/6+. This profile overlaps with that of mesothelial cells. This study of high-grade breast carcinomas was undertaken to determine the expression of mesothelial markers. METHODS AND RESULTS: Immunohistochemistry was performed on 23 basal-like breast carcinomas and 30 high-grade breast carcinomas with variable ER, PR and HER2 expression. The incidence of staining of CK5/6, CK14, calretinin, Wilms' tumour 1 (WT1), thrombomodulin and epithelial membrane antigen was assessed statistically. CK14 staining was more specifically associated with triple-negative tumours than CK5/6. Calretinin positivity was statistically associated with basal-like carcinomas. WT1 and thrombomodulin expression was infrequent and limited to a small number of non-basal carcinomas. CONCLUSIONS: There is an overlap between the immunophenotype of mesothelial cells and that of basal-like carcinomas of breast. Positive calretinin and CK5/6 are not specific, and may be seen in both mesothelial cells and basal-like breast carcinomas. Negative ER and PR of basal carcinomas may also bias the observer against a breast origin. However, other negative mesothelial markers, such as WT1 and thrombomodulin, may help point to the correct diagnosis. PMID- 22092408 TI - In breast cancer, a high ratio of tumour-infiltrating intraepithelial CD8+ to FoxP3+ cells is characteristic for the medullary subtype. AB - AIMS: Medullary breast cancer (MBC) is a biologically distinct subtype of breast cancer characterized by prominent lymphocytic infiltrates and a favourable clinical outcome. Tumour-infiltrating CD8+ effector T cells may contribute to the good prognosis of this type of cancer; however, certain subtypes of lymphocyte, such as FoxP3+ regulatory T cells (Tregs), can also suppress antitumour immunity. METHODS AND RESULTS: We determined tumour infiltration by FoxP3+, CCL22+ and CD8+ cells in paraffin-embedded sections of MBC, and, as a reference, in samples of grade 3 ductal, lobular and mucinous breast cancer. All analysed MBCs were strongly infiltrated by FoxP3+ cells, whereas only weak infiltrates were detected in ductal or lobular breast cancer. This finding was unexpected, given the good prognosis of MBC. Strikingly, the number of CD8+ T cells exceeded the number of FoxP3+ cells in MBC (ratio of CD8+ to FoxP3+ cells of 2.6), whereas equal amounts of both cell types were found in ductal breast cancer (ratio of CD8+ to FoxP3+ cells of 1.1). In both types of breast cancer, we also detected cells expressing the Treg-attracting chemokine CCL22. CONCLUSIONS: In breast cancer, a predominance of tumour-infiltrating CD8+ over FoxP3+ cells was observed in MBC. Thus, the ratio of CD8+ to FoxP3+ cells rather than the absolute number of intratumoral FoxP3+ cells may be predictive for the clinical outcome of cancer. PMID- 22092409 TI - Human epidermal growth factor receptor 2 (HER2) immunoreactivity: specificity of three pharmacodiagnostic antibodies. AB - AIMS: The availability of specific antibody-based test systems is essential to testing of HER2 protein expression. Here, we mapped epitopes recognized by three pharmacodiagnostic HER2 antibodies and investigated their specificity towards peptides and fusion proteins homologous to the intracellular domains of HER1, HER2, HER3 and HER4. The investigated antibodies were PATHWAY((r)) HER2 (clone 4B5; Ventana Medical Systems Inc., Tucson, AZ, USA), HercepTestTM (Dako Denmark A/S, Glostrup, Denmark), and Oracle((r)) HER2 (clone CB11; Leica Microsystems GmbH, Wetzlar, Germany). METHODS AND RESULTS: Epitopes were mapped using the alanine scanning method. Specificity was investigated in immunohistochemical stainings, competitive enzyme-linked immunosorbent assay (ELISA) and immunoblotting. All three antibodies reacted with HER2 proteins and peptides in immunohistochemical stainings, ELISA and immunoblotting. PATHWAY((r)) HER2 also stained HER4-expressing cells, reacted with HER4 peptide in ELISA and detected HER4 fusion protein in an immunoblot. Oracle((r)) HER2 weakly detected HER4 in immunohistochemical stainings, whereas the HercepTestTM antibody showed no cross reactivity with other HER proteins. CONCLUSION: Our study shows that the PATHWAY((r)) HER2 antibody can bind HER4 peptides and fusion proteins in three different experimental settings. This should be investigated further to determine whether binding of HER4 also occurs in tissue samples and if such binding would have implications for therapy decisions for breast cancer patients. PMID- 22092410 TI - Dual-colour chromogenic in-situ hybridization is a potential alternative to fluorescence in-situ hybridization in HER2 testing. AB - AIM: Dual-colour chromogenic in-situ hybridization (dc-CISH) is an emerging methodology for characterizing genomic alterations. This study was aimed at evaluating the performance of a dc-CISH kit (ZytoVision) in determining human epidermal growth factor receptor 2 (HER2) status in breast cancer. METHODS AND RESULTS: Two hundred and twenty-eight invasive breast carcinomas arranged in tissue microarrays were analysed in parallel with dc-CISH, fluorescence in-situ hybridization (FISH), and immunohistochemistry. Of 227 tumours with available FISH and dc-CISH results, HER2 amplification and non-amplification were detected in 49 (21.6%) and 178 (78.4%) tumours, respectively, by both assays. The concordance between dc-CISH and FISH results showed 100% agreement (kappa coefficient=1.00). Immunohistochemically, 162 (71%), 25 (11.0%) and 41 (18%) tumours were scored 0/1+, 2+, and 3+, respectively. The corresponding results with both FISH and dc-CISH demonstrated HER2 amplification in two (3.2%), nine (36%) and 38 (93%) tumours, respectively. Complete consensus among these three methods was observed in 197 cases, representing 98% of all 3+ and 0/1+ tumours (kappa-coefficient=0.92). Confirmatory testing of 25 2+ tumours showed complete consensus between FISH and dc-CISH. CONCLUSIONS: dc-CISH is a promising alternative to FISH in HER2 testing, and the single-institute incidence of HER2 amplification in breast cancer in Taiwan is 21.2%. PMID- 22092411 TI - Improved detection of mycobacteria species in formalin-fixed tissue sections. AB - AIMS: To develop an antibody broadly reactive against mycobacterial species, which will improve detection of mycobacteria in tissue sections by immunohistochemistry (IHC). METHODS: A sheep antisera was developed by immunization with multiple mycobacteria, and was tested by IHC against a range of mycobacteria in tissues from many species, as well as negative tissue controls and other bacteria. RESULTS: The sheep antiserum, MAS-01, reacted with all 18 mycobacterial species tested, but did not react with uninfected inflammatory tissues. Although MAS-01 cross-reacted with two microbial genera which are related to mycobacteria (Corynebacteria and Proprionibacteria), it did not with Nocardia or Actinomyces. The antibody was more sensitive than the Ziehl-Neelsen stain for detection of tissue mycobacteria, and shortened the time required to identify these infections. CONCLUSION: The MAS-01 antiserum will facilitate rapid identification of tissue mycobacterial infection by histopathologists. PMID- 22092414 TI - Histopathology sampling of radical prostatectomy specimens: representative or entire submission? PMID- 22092416 TI - Regional differences in injury incidence in European professional football. AB - The objective of this study was to investigate regional differences in injury incidence in men's professional football in Europe. A nine-season prospective cohort study was carried out between 2001-2002 and 2009-2010 involving 1357 players in 25 teams from nine countries. Teams were categorized into different regions according to the Koppen-Geiger climate classification system. Teams from the northern parts of Europe (n = 20) had higher incidences of injury overall [rate ratio 1.12, 95% confidence interval (CI) 1.06 to 1.20], training injury (rate ratio 1.16, 95% CI 1.05 to 1.27), and severe injury (rate ratio 1.29, 95% CI 1.10 to 1.52), all statistically significant, compared to teams from more southern parts (n = 5). In contrast, the anterior cruciate ligament injury incidence was lower in the northern European teams with a statistically significant difference (rate ratio 0.43, 95% CI 0.25 to 0.77), especially for noncontact anterior cruciate ligament injury (rate ratio 0.19, 95% CI 0.09 to 0.39). In conclusion, this study suggests that there are regional differences in injury incidence of European professional football. However, further studies are needed to identify the underlying causes. PMID- 22092417 TI - Involvement of upper cheek sagging in nasolabial fold formation. AB - BACKGROUND: Nasolabial folds are a well-known feature of aging, but the mechanism of their formation remains unclear. OBJECTIVES: To clarify the mechanism of nasolabial fold formation, we established grading criteria for severity and explored the influence of dermal elasticity and subcutaneous adipose mass. We also investigated the involvement of facial morphological changes, such as wrinkling and sagging. METHODS: Faces of 108 healthy Japanese female volunteers (age range: 20-60) were photographed at the angle of 45 degrees , and a six-grade photograph-based grading scheme for nasolabial fold severity was established and evaluated. In 70 Japanese female volunteers (middle-aged: 30-50), dermal elasticity was measured with a Cutometer MPA 580(r) and subcutaneous adipose layer thickness was measured by ultrasound using a Prosound alpha 5(r). RESULTS: Nasolabial fold severity was significantly and positively correlated with age in subjects in their twenties to sixties (R = 0.777, P < 0.001). Nasolabial folds were drastically reduced, or disappeared, when the facial position was changed (subjects lay down instead of sitting) to reduce sagging; only 13.8% of subjects showed fixed wrinkles at the positions of the nasolabial folds after the facial position change. Nasolabial fold severity in middle-aged volunteers was significantly and negatively correlated with dermal elasticity parameters, i.e., net elasticity excluding viscoelastic creep (Ur/Ue), overall elasticity including creep and creep recovery (Ua/Uf), ratio of elastic recovery to total deformation (Ur/Uf), and the negative value of the amount of deformation that did not recover to the original state [-Uf-Ua)], all of which were significantly and negatively correlated with age. Subcutaneous adipose layer thickness was significantly and negatively correlated with dermal elasticity parameter Ua/Uf, and also significantly and positively related to nasolabial fold severity (R = 0.285, P < 0.017). CONCLUSIONS: Nasolabial fold severity increases with decreasing dermal elasticity and with increment of the subcutaneous adipose layer. These changes might induce sagging formation in the upper cheek area, promoting fold formation at the border between the inner and outer nasolabial areas. PMID- 22092418 TI - Non-surgical periodontal therapy improves oral health-related quality of life. AB - AIM: The influence of non-surgical periodontal therapy on oral health-related quality of life (OHQoL) was investigated. MATERIALS AND METHODS: Sixty-five Chinese adults (25 men, mean 47.4 years) with moderate-to-advanced chronic periodontitis were recruited. All received oral hygiene instructions (OHI) and non-surgical periodontal treatment in a quadrant-wise approach, followed by recalls at 1, 3, 6, 9 and 12 months post treatment, when OHI and prophylaxis were repeated. Clinical parameters were recorded, and oral health impact profile short form (OHIP-14S) was administered at all time points. RESULTS: Moderate-to-deep sites (>=4 mm) decreased from 31.0% to 3.0% at 12 months post treatment (p < 0.005) which corresponded well with reductions in plaque, 72.8% to 25.4% (p < 0.005) and bleeding on probing, 86.3% to 32.0% (p < 0.005). Median OHIP-14S scores gradually reduced from 17 at baseline to 14 over the first 6 months and remained plateaued at 12-month post treatment (p < 0.005). Improvements in subdomains of physical pain, psychological discomfort and psychological disability accounted for the changes. CONCLUSION: This study demonstrates that OHQoL, in particular, pain and psychological subdomains, improvement was associated with non-surgical periodontal therapy responses. Clinicians could capitalize upon the positive psychological OHQoL impacts of mechanical periodontal treatment for subsequent patient-centred motivation during maintenance therapy. PMID- 22092419 TI - Does three-dimensional imaging offer a financial benefit for treating maxillary molars with furcation involvement? A pilot clinical case series. AB - AIM: To assess the financial benefit of cone beam computed tomography (CBCT) for the treatment options of maxillary molars including periodontal surgery and extraction followed by implant placement. MATERIAL AND METHODS: Twelve patients with generalized chronic periodontitis were recruited, and CBCT was performed in maxillary molars (n = 22) with clinical furcation involvement and increased probing pocket depths. Treatment recommendations were either based on conventional periodontal diagnostics (clinical examinations and periapical radiographs), or based on the additional CBCT data. Clinical recommendations comprised a minimal (e.g. supportive periodontal treatment) and a maximal invasive therapy (e.g. extraction and implant placement), and these were compared with CBCT-based recommendations. According to the Swiss dental tariff structure, the probabilities of saving costs or time, and the numbers needed to treat were analysed with an empirical cumulative distribution function. RESULTS: Average cost reduction from CBCT amounted to CHF 915 +/- 1470 and saved 136 +/- 217 min. Greatest reductions were found with maximal invasive clinically based treatment decisions (CHF 1566 +/- 1840), particularly for second molars (CHF 2485 +/- 2226). To compensate CBCT costs, 1.7 subjects were needed to treat to at least break even. CONCLUSIONS: Data from CBCT facilitated a reduction in treatment costs and time for periodontally involved maxillary molars in Switzerland. Based on these cost analyses, however, CBCT as additional diagnostic measure is justified only when more invasive therapies are planned. PMID- 22092420 TI - Kruger strict morphology and post-thaw progressive motility in cryopreserved human spermatozoa. AB - The purpose of this prospective study was to evaluate Kruger strict morphology and conventional semen analysis in predicting cryosurvival and the progressive motility recovery rate of frozen spermatozoa. Our study included 56 semen samples with >10 million spermatozoa per ejaculate. The main outcome measures were conventional semen analysis, strict morphology analysis by the Kruger method, cryosurvival rate and post-thaw sperm motility. A significant reduction in sperm motility after cryopreservation was demonstrated. The freeze-thawing process caused a 66% reduction in rapid progressive motile spermatozoa, a 45% reduction in slow progressive motile spermatozoa and a 2% reduction in nonprogressive motile spermatozoa. The cryosurvival and progressive motility recovery rates were not correlated with parameters of conventional semen analysis, such as sperm concentration, motility, WHO morphology and total motile count, but the progressive motility recovery rate was significantly correlated with the percentage of spermatozoa exhibiting Kruger normal morphology (P = 0.028). The recovery rate of rapidly progressive motility was profoundly decreased compared with slow progressive motility following the frozen-thaw procedure of semen. Kruger strict morphology assessment was a better predictor of the progressive motility recovery rate following the freezing-thaw procedure than parameters of conventional semen analysis. PMID- 22092421 TI - The ethics of international studies. PMID- 22092422 TI - Physical activity among South Asian Indian immigrants: an integrative review. AB - OBJECTIVE(S): The aim of this research review was to portray the correlates of lifestyle physical activity (PA) behavior of healthy South Asian Indian (SAI) immigrants comprehensively by identifying, synthesizing, and critically analyzing the existing research literature. DESIGN AND SAMPLE: An integrative review methodology was used. The sample included 11 cross-sectional and 4 qualitative studies. MEASURES: The physical activity framework for SAI immigrants guided the development of data collection tools that included study measures of PA and background (current health, acculturation, discrimination, social support, environmental) and intrapersonal (motivation) correlates of PA. RESULTS: Regardless of the PA measure used, all studies reported low PA levels in at least 40% of the participants. The correlates of PA most often studied were sociodemographic variables, current health, and acculturation; female sex; poorer health; and less time since immigration. Few studies focused on social support, environmental factors, or included dynamic motivational factors. CONCLUSIONS: Increased knowledge of the factors that impact lifestyle PA is needed so that public health nurses can develop targeted interventions to increase the lifestyle PA of SAI immigrants at risk for cardiovascular disease, diabetes, and central obesity. PMID- 22092423 TI - Undermining of nutrition and exercise decisions: experiencing negative social influence. AB - OBJECTIVE: The objective of this research was to assess social undermining (negative interpersonal influence) on health behaviors in a large sample of Internet users. DESIGN AND SAMPLE: This study used a cross-sectional descriptive design with an online survey that yielded quantitative and qualitative data. A total of 6,923 individuals received invitations and 1,270 participants completed the survey (18.3% response rate). Respondents completing at least 1 qualitative question were retained for analysis (n=1,158). The sample had more females (75.9%) than males (24.1%) and an average age of 42.9 years (SD+/-12.4). MEASURES: Participants described experiences and perceptions of undermining. Content analysis was used to identify themes, and responses were coded after establishing intercoder reliability (kappa=.92). Coded responses were correlated with gender, body mass index, and satisfaction with weight. RESULTS: Many respondents reported that they were affected by undermining. The most common sources of undermining were family and significant others. Individuals satisfied with their current weight were more likely to resist undermining. Many suggested undermining might result from jealousy or others' guilt over their own decisions. CONCLUSIONS: Undermining of healthy behaviors is an important issue for public health researchers and practitioners as it pertains to patient counseling and the development of strategies for resisting undermining. PMID- 22092424 TI - Do infertile women and government staff differ in the evaluation of infertility related Web sites? AB - OBJECTIVE: To investigate the evaluation of local government Web sites carrying information on infertility by infertile women and by government staff. In particular, the study investigated whether the women and staff differed with respect to the information they rate as important and their self-reported satisfaction with the Web sites. DESIGN AND SAMPLE: Cross-sectional descriptive study. Sixty-two local government staff members, of whom 46 were public health nurses managing subsidy programs for infertility treatment in the Hokuriku region of Japan, and 84 infertile women attending local clinics. MEASURES: We measured the level of satisfaction with the local government Web sites and perceptions about the importance of each type of content. Data were descriptively analyzed, as well as by factor analysis and multiple regression analysis. RESULTS: Local government Web sites were analyzed with respect to information about the treatment, details of the subsidy program, psychological support, and procedures for making a subsidy application. CONCLUSIONS: The women rated information on the treatment and details of the subsidy programs as important. There was no difference of satisfaction with the Web sites between the infertile women and the staff. Local government staff need to provide reliable data for women who are seeking information on infertility treatment. PMID- 22092425 TI - Feasibility of using the Omaha System to represent public health nurse manager interventions. AB - OBJECTIVE: To test the feasibility of representing public health nurse (PHN) manager interventions using a recognized standardized nursing terminology. DESIGN AND SAMPLE: A nurse manager in a Midwest local public health agency documented nurse manager interventions using the Omaha System for 5 months. ANALYTIC STRATEGY: The data were analyzed and the results were compared with the results from a parallel analysis of existing PHN intervention data. RESULTS: Interventions for 79 "clients" (projects, teams, or individuals) captured 76% of recorded work hours, and addressed 43% of Omaha System problems. Most problems were addressed at the "community" level (87.1%) versus the "individual" level (12.9%). CONCLUSIONS: Nursing practice differed between the 2 knowledge domains of public health family home visiting nursing and public health nursing management. Standardized nursing terminologies have the potential to represent, describe, and quantify nurse manager interventions for future evaluation and research. PMID- 22092426 TI - Effects of visiting nurses' individually tailored education for low-income adult diabetic patients in Korea. AB - OBJECTIVE: To describe the effects of individually tailored education by visiting nurses for low-income adult diabetic patients. DESIGN AND SAMPLE: This one-group pretest-posttest study included 96 newly registered low-income adult diabetic patients in a public health center in DJ-gu (similar to a county in the United States) in 2006; the patients met the selection criteria. MEASURES: Diabetes knowledge, self-management, and blood glucose levels were compared before and after education. INTERVENTION: 15 visiting nurses delivered individually tailored education for 60-90 min/month for 7 months. RESULTS: After education, diabetes knowledge (p<.001) and self-management in all categories of lifestyle (p<.001), diet (p<.001), exercise (p<.001), foot care (p<.001), medication (p=.004), and insulin therapy (p=.022) significantly improved. The mean fasting blood glucose (FBG) level decreased by 14.53 mg/dl; this decrease was insignificant (p=.117). However, the relationship between education and FBG levels was significant (chi(2)=40.11, p=.005). CONCLUSIONS: Tailored education effectively improved the patients' knowledge of diabetes and self-management. Therefore, regular, individually tailored education on a long-term basis by visiting nurses can provide essential education to low-income adult diabetic patients for maintaining self-management. PMID- 22092427 TI - Motorcycle rider training for the prevention of road traffic crashes: a review synopsis. PMID- 22092428 TI - Stage-based interventions for smoking cessation: a review synopsis. PMID- 22092429 TI - Cognitive interviews to test and refine questionnaires. AB - Survey data are compromised when respondents do not interpret questions in the way researchers expect. Cognitive interviews are used to detect problems respondents have in understanding survey instructions and items, and in formulating answers. This paper describes methods for conducting cognitive interviews and describes the processes and lessons learned with an illustrative case study. The case study used cognitive interviews to elicit respondents' understanding and perceptions of the format, instructions, items, and responses that make up the Diabetes Symptom Self-Care Inventory (DSSCI), a questionnaire designed to measure Mexican Americans' symptoms of type 2 diabetes and their symptom management strategies. Responses to cognitive interviews formed the basis for revisions in the format, instructions, items, and translation of the DSSCI. All those who develop and revise surveys are urged to incorporate cognitive interviews into their instrumentation methods so that they may produce more reliable and valid measurements. PMID- 22092430 TI - Cluster analysis identifies subpopulations for health promotion campaign design. AB - While health communication campaigns have been effective in addressing a variety of health concerns, even broadly successful campaigns can miss particular subpopulations. The statistical technique of cluster analysis, which makes it possible to group individuals based on sets of identifying variables, is a statistical method that could prove useful in the design of more effective communication campaigns. This paper illustrates the use of cluster analysis to group women based on their (1) prepregnancy weight, (2) weight gain during pregnancy, and (3) weight retention after giving birth as it relates to the process of targeting subpopulations and developing more effective health communication campaigns and interventions. The implications of cluster analysis, from guiding additional formative research to development of health communication strategies, are discussed. PMID- 22092431 TI - A concept analysis of suicidal behavior. AB - OBJECTIVE: Suicidal behavior is a significant global public health problem. Despite this, many health care professionals remain unaware of the distinction among suicidal behavior, self-mutilation, and deliberate self-harm. The aim of this study was to conduct a concept analysis of suicidal behavior. METHOD: Walker and Avant's 8-step method of concept analysis was used to examine the concept of suicidal behavior. Sources for analysis were identified using a systematic search of Medline, CINAHL, ProQuest Nursing & Allied Health Source, and the reference lists of related journal articles. RESULTS: Suicidal behavior was found to be associated with a constellation of external hazards and internal crises, lack of coping mechanisms and social support structures, and degree of suicidal intent, which, in the worst-case scenario, results in successful suicide. The antecedents of suicidal behavior are vulnerability characteristics that make painful events seem unbearable, and the consequences are death or failed suicide. In cases of failure, the medical consequences may be serious and long lasting. CONCLUSIONS: Defining the concept of suicidal behavior provides a basis for public health nurses to better understand suicidal behavior, thus improving their ability to care for suicidal patients during home visits. PMID- 22092432 TI - Four responsibilities of the tuberculosis nurse, circa 1919. AB - Specialization in public health nursing practice was beginning to occur early in the 20th century. In a 1919 paper published in The Public Health Nurse, Mary Van Zile argued that there were four essential functions of the tuberculosis nurse. Later that year, Janet Scott reported on the results of a partnership between the tuberculosis dispensary, the Lions Club, and other Oklahoma City community organizations, which illustrated the application of Van Zile's principles, and the expanding scope of public health nursing practice. PMID- 22092433 TI - Detecting metabolic activities in single cells, with emphasis on nanoSIMS. AB - Investigating the contribution of microbial populations to biochemical processes of global significance is challenging as there are few approaches that can detect microbial metabolic activities on single-cell level. Given the widespread distribution and importance of microorganisms in elemental transformations, improved methods for measuring microbial activities in naturally occurring microbial communities is essential. In this article, microautoradiography (MAR), Raman microspectroscopy, and Secondary Ion Mass Spectrometry (SIMS) and their combination with isotope labeling and molecular genetic methods for cell identification (i.e. FISH and related methods) are reviewed. We focus our review on the application of MAR-FISH, Raman-FISH, and FISH-SIMS to environmental samples, with a more detailed description of the use of nanoSIMS-based methodologies to identify, quantify, and visualize the incorporation of labeled substrates of single microorganisms in complex microbial communities. We highlight examples from the marine habitat. In addition, relevant technical aspects as well as important considerations concerning sample preparation and handling are presented. We conclude with a perspective on the usefulness of such tools to study the role of microorganisms in biogeochemical cycling from micron to global scales. PMID- 22092434 TI - Expression of apoptosis regulatory proteins p53, bcl-2 and bax in recurrent aphthous ulceration. AB - BACKGROUND: Recurrent aphthous ulceration (RAU) is considered to be an acute inflammatory disease of unknown pathogenesis. Apoptosis may represent an important event in the control of inflammation. OBJECTIVES: The aim of this study was to investigate apoptosis process in RAU using immunohistochemistry. METHODS: We studied the expression and location of p53, bcl-2 and bax in ulcerated lesions clinically diagnosed as RAU (n = 12) and compared it with that of oral clinically normal mucosa (n = 6) and of other inflammatory chronic disease such as oral fibrous inflammatory hyperplasia (FIH; n = 18). RESULTS: Significant statistically differences (n < 0.05) in p53 expression were noticed in RAU when compared with normal mucosa. No significant statistically differences (P > 0.05) were noticed between FIH and RAU. Bcl-2 and bax did not show remarkable differences between groups. CONCLUSIONS: Taken together, the data suggest that RAU induces p53 immunoexpression. Therefore, the protein might be related to the aetiopathogenesis of the ulcerated oral lesions. PMID- 22092435 TI - Effects of adult inpatient group psychotherapy on attachment characteristics: an observational study comparing routine care to an untreated comparison group. AB - This study investigated the changes in attachment characteristics of patients undergoing inpatient group psychotherapy in routine care. We collected data from 265 consecutively recruited patients and 260 non-clinical control persons using self-report measures of attachment, depression, and socio-demographic characteristics. The effects of treatment on patients were analyzed using propensity score techniques (propensity strata and logit-transformed propensity scores) in combination with a generalized analysis of covariance. A moderate increase of attachment security was found which could be attributed to a decrease both in attachment anxiety and avoidance. Pre-post improvements in attachment with regard to romantic partnerships were stable after a 1-year follow-up. Furthermore, we found significant treatment-covariate interactions indicating that subjects with particularly high treatment propensities (propensities were highly correlated with depression and attachment anxiety) improved the most in terms of attachment security. Our results are encouraging for psychotherapeutic practice in that they provide evidence that long-term attachment improvements can be reached via psychotherapy. Our results will also provide a sound basis for future studies in the field of clinical attachment research, e.g., studies examining whether improved attachment security is correlated to symptom improvements in different psychological disorders. PMID- 22092436 TI - Histomorphometric analysis of sinus augmentation using bovine bone mineral with two different resorbable membranes. AB - OBJECTIVE: The purpose of this study was to compare the effects of two different resorbable collagen membranes on new bone formation after sinus grafts with anorganic bovine bone mineral (BBM). MATERIALS AND METHODS: For 64 patients presenting with an initial residual bone height <=4 mm at the posterior maxilla, the sinus floors were grafted with BBM (Bio-Oss). The lateral windows were covered by one of the two bio-resorbable membranes, Bio-Arm or Bio-Gide. The histomorphometric data were obtained 7-15 months after sinus augmentation at the time of the implant installation. RESULTS: The core biopsy specimens of Bio-Arm (n = 37 sites) and Bio-Gide group (n = 22 sites) were compared. The results showed that the BBM particles were in direct contact with the newly formed bone in all cases. In histomorphometric analysis, the Bio-Gide group showed significantly higher new bone formation (33.3 +/- 12%) compared with the Bio-Arm group (26.3 +/- 8.1%) (P < 0.05). All the implants survived successfully after a mean follow-up of 35.3 months (range 22-63 months) in the Bio-Arm group and 55.5 months (range 35-66 months) in the Bio-Gide group. The amount of new bone in the specimens did not significantly correlate with the residual bone height at the time of surgery or the length of the healing period. CONCLUSIONS: The type of resorbable membrane did not readily affect the long-term survival of the implants at the grafted sinus. On the other hand, Bio-Gide group showed more new bone formation than the Bio-Arm group, which implied that the function of the membrane can influence the remodeling of the grafted sinus. As the amount of residual bone substitute particle had not decreased significantly over time, the results suggest that the BBM was rarely resorbable for at least 15 months after the surgery. PMID- 22092437 TI - An increase in serum tryptase even below 11.4 ng/mL may indicate a mast cell mediated hypersensitivity reaction: a prospective study in Hymenoptera venom allergic patients. AB - BACKGROUND: During a systemic hypersensitivity reaction (SR), an increase in serum tryptase compared to the baseline value is an indicator of mast cell activation, most often due to an IgE-mediated mechanism. OBJECTIVE: To study the relevance of an increase in serum tryptase below the upper normal value of 11.4 ng/mL. METHODS: Serum tryptase levels were measured in 35 patients with Hymenoptera venom hypersensitivity before and during venom exposure. Of these, 20 developed SR to stings or following venom injections during immunotherapy (reactors), while 15 tolerated reexposure to stings or venom injections during immunotherapy without SR (non-reactors). Serum tryptase was estimated at 2, 5 and 24 h after exposure and was compared to a baseline value obtained before or at least 72 h after exposure. RESULTS: Considering circadian variation of serum tryptase, a relative increase to >=135% of the baseline value (relative delta bound) was defined to indicate mast cell activation. Such an increase was observed in 17 of 20 reactors (85%), but none of 15 non-reactors. A serum tryptase of >=11.4 ng/mL following venom exposure was observed in eight of the 20 reactors (40%) and 2 (13.3%) of the 15 non-reactors. Both these non-reactors also had an elevated baseline serum tryptase. CONCLUSIONS AND CLINICAL RELEVANCE: Serum tryptase values obtained during a suspected hypersensitivity reaction must always be compared to a baseline value. A relative tryptase increase to >=135% of the baseline value during a suspected hypersensitivity reaction indicates mast cell activation even below 11.4 ng/mL. PMID- 22092438 TI - Genetic difference but functional similarity among fish gut bacterial communities through molecular and biochemical fingerprints. AB - Considering the major involvement of gut microflora in the digestive function of various macro-organisms, bacterial communities inhabiting fish guts may be the main actors of organic matter degradation by fish. Nevertheless, the extent and the sources of variability in the degradation potential of gut bacterial communities are largely overlooked. Using Biolog EcoplateTM and denaturing gradient gel electrophoresis (DGGE), we explored functional (i.e. the ability to degrade organic matter) and genetic (i.e. identification of DGGE banding patterns) diversity of fish gut bacterial communities, respectively. Gut bacterial communities were extracted from fish species characterized by different diets sampled along a salinity gradient in the Patos-Mirim lagoons complex (Brazil). We found that functional diversity was surprisingly unrelated to genetic diversity of gut bacterial communities. Functional diversity was not affected by the sampling site but by fish species and diet, whereas genetic diversity was significantly influenced by all three factors. Overall, the functional diversity was consistently high across fish individuals and species, suggesting a wide functional niche breadth and a high potential of organic matter degradation. We conclude that fish gut bacterial communities may strongly contribute to nutrient cycling regardless of their genetic diversity and environment. PMID- 22092439 TI - Listeria monocytogenes tyrosine phosphatases affect wall teichoic acid composition and phage resistance. AB - Tyrosine phosphatase (PTP)-like proteins exist in many bacteria and are segregated into two major groups: low molecular weight and conventional. The latter group also has activity as phosphoinositide phosphatases. These two kinds of PTP are suggested to be involved in many aspects of bacterial physiology including stress response, DNA binding proteins, virulence, and capsule/cell wall production. By annotation, Listeria monocytogenes possesses two potential low molecular weight and two conventional PTPs. Using L. monocytogenes wild-type (WT) strain 10403S, we have created an in-frame deletion mutant lacking all four PTPs, as well as four additional complemented strains harboring each of the PTPs. No major physiological differences were observed between the WT and the mutant lacking all four PTPs. However, the deletion mutant strain was resistant to Listeria phages A511 and P35 and sensitive to other Listeria phages. This was attributed to reduced attachment to the cell wall. The mutant lacking all PTPs was found to lack N-acetylglucosamine in its wall teichoic acid. Phage sensitivity and attachment was rescued in a complemented strain harboring a low molecular weight PTP (LMRG1707). PMID- 22092440 TI - The anterior loop of the inferior alveolar nerve: prevalence, measurement of its length and a recommendation for interforaminal implant installation based on cone beam CT imaging. AB - OBJECTIVES: Interforaminal implant surgery requires anatomical knowledge of the area and adequate information on the location of the various landmarks of significance such as the mental foramen, the anterior loop of the inferior alveolar nerve and the mandibular incisive canal. Cone beam computed tomography (CBCT) is a relatively new imaging modality that provides a multi-dimensional view of the facial skeleton with, in most instances, lower radiation dose to the patient compared to medical CT. The present study aims to use CBCT to identify and measure variation in the presence and extent of the anterior loop of the inferior alveolar nerve. This information may be used to provide recommendations to the surgeon without access to a 3D scan of the dento-alveolar region. MATERIAL AND METHODS: Ninety-three patients scanned with a Newtom VG device for a variety of clinical indications were included in this retrospective study. Using the multiplanar capabilities of the device's software the prevalence and length of the anterior loop was assessed. RESULTS: The results show that an anterior loop could be identified in 48% of the cases with a mean length (range) of 0.89 mm (0 5.7). CONCLUSIONS: In almost half of the surveyed cases an anterior loop was present. Even though in 95% of the study cases the loop was <3 mm, a 100% safety margin in the placement of anterior mandibular implants, in the absence of a CBCT scan, would only be achieved with a distance of 6 mm between the anterior border of the mental foramen and the most distal interforaminal implant fixture. PMID- 22092441 TI - Feeding frequency and survival of Anopheles gambiae in a rice-growing area in Ghana. AB - Mortality rates, determined by dissection, of predominantly M form female Anopheles gambiae (Diptera: Culicidae) were estimated. Mosquitoes were collected in tent traps and light traps in an irrigation project village in Ghana in June and July 2010, when much of the area was flooded. Both M and S form larvae were collected from rice fields (74 of 80 specimens were M form). Adults were collected in equal proportions from the two traps (90 of 107 specimens from the light trap and 106 of 116 specimens from the tent trap were M form). During the study, collection numbers rose from 105 to 972 per night. A total of 1787 of the 15 431 An. gambiae collected were dissected. Of these, 953 (53%) were found to have taken their first bloodmeal, either as virgins or following mating. The age profiles of mosquitoes collected alive and dead, respectively, were similar. Eighteen of 2933 (0.61 +/- 0.49%) specimens were found to be positive for sporozoites in an enzyme-linked immunosorbent assay (ELISA). Lagged cross correlations among the different age groups implied that the mosquitoes fed on days 2 and 4 following emergence prior to oviposition and every 2.65 +/- 0.17 days thereafter. The best model to describe the observed population patterns implied a daily mortality of 84%. The results are discussed in relation to possible mosquito control measures for the village. PMID- 22092442 TI - Piezoelectric vs. conventional implant site preparation: ex vivo implant primary stability. AB - OBJECTIVES: This study aims to determine differences in primary stability between implants placed in cortical bone following Piezoelectric or conventional site preparation, as assessed by resonance frequency analysis (RFA) and reverse torque testing (RTT). MATERIAL AND METHODS: Four fresh bovine ribs were acquired and surgical guides fabricated with five sites per rib (n = 20), for proper site preparation. Implant sites were prepared via conventional drilling technique as per manufacturer's instruction (Implantium) or via Piezoelectric (Mectron) implant site preparation using the Implant Prep kit. Twenty 10 mm long, 3.6 mm diameter Implantium implants were placed with 35 Ncm torque; 10 implants per preparation method. RFA was assessed via the Osstell Mentor. Five values were taken per implant. All implants where subjected to a reverse torque in increasing increments of 5 until 50 Ncm force was reached. RESULTS: The five RFA values per site were averaged and plotted by placement technique. A paired t-test statistical analysis was run. The average RFA values showed no statistical significance between the 10 test (RFA = 69.04 +/- 5.11) and 10 control (RFA = 70.94 +/- 6.41) sites (P > 0.05). All implants in both groups withstood RTT up to 50 Ncm force without movement and thus showed no statistical differences. CONCLUSION: Results of this ex vivo study imply that the Piezoelectric implant site preparation affords similar primary implant stability in comparison to conventional rotary instrumentation in cortical bone. PMID- 22092443 TI - Digital correction of motion artefacts in microscopy image sequences collected from living animals using rigid and nonrigid registration. AB - Digital image analysis is a fundamental component of quantitative microscopy. However, intravital microscopy presents many challenges for digital image analysis. In general, microscopy volumes are inherently anisotropic, suffer from decreasing contrast with tissue depth, lack object edge detail and characteristically have low signal levels. Intravital microscopy introduces the additional problem of motion artefacts, resulting from respiratory motion and heartbeat from specimens imaged in vivo. This paper describes an image registration technique for use with sequences of intravital microscopy images collected in time-series or in 3D volumes. Our registration method involves both rigid and nonrigid components. The rigid registration component corrects global image translations, whereas the nonrigid component manipulates a uniform grid of control points defined by B-splines. Each control point is optimized by minimizing a cost function consisting of two parts: a term to define image similarity, and a term to ensure deformation grid smoothness. Experimental results indicate that this approach is promising based on the analysis of several image volumes collected from the kidney, lung and salivary gland of living rodents. PMID- 22092444 TI - Reflections on a sticky situation: how surface contact pulls the trigger for bacterial adhesion. AB - Adhesion of bacterial cells to surfaces can be mediated by a wide variety of extracellular structures, which can either recognize specific molecular motifs or adhere in non-specific ways to multiple types of surfaces. The attachment is thought to be highly regulated, but the underlying sensory mechanism(s) are poorly understood. In the alpha-proteobacterium Caulobacter crescentus, the formation of adhesive organelles is 'hardwired' into the cell cycle regulatory circuitry. In this issue of Molecular Microbiology, Li et al. (2011) employed this model organism to examine the adhesion process and the transition from temporary to permanent attachment using total internal reflection fluorescence (TIRF) microscopy. Surprisingly, they observed that adhesin production was not only under developmental control, but was also stimulated by surface contact. Initial reversible contact of the pili with the surface was followed by flagellum rotation arrest and subsequent induction of the holdfast to allow irreversible surface adhesion. These findings demonstrate that Caulobacter produces its holdfast only at the appropriate time for surface attachment, preventing premature export of the adhesin, which could then be inactivated by 'curing' or be masked by occluding particles. Importantly, their results support the notion that the flagellum serves as a mechanosensor for adhesion. PMID- 22092445 TI - Ten-year results of a three arms prospective cohort study on implants in periodontally compromised patients. Part 2: clinical results. AB - OBJECTIVES: The aim of this study was to compare long-term outcomes of implants placed both in patients treated for periodontitis and in periodontally healthy patients (PHP). MATERIAL AND METHODS: One hundred and twelve partially edentulous patients were consecutively enrolled in private specialist practice and divided into three groups according to their initial periodontal condition: PHP, moderately periodontally compromised patients (PCP) and severely PCP. Implants were placed to support fixed prostheses, after successful completion of initial periodontal therapy [full-mouth plaque score (FMPS) <25%, full-mouth bleeding score (FMBS) <25%]. At the end of active periodontal treatment (APT), patients were asked to follow an individualized supportive periodontal therapy (SPT) program. Diagnosis and treatment of peri-implant biological complications was performed according to cumulative interceptive supportive therapy. At 10 years, clinical measures were recorded by two calibrated operators, blinded to the initial patient classification, on 101 patients, as 11 were lost to follow-up. The number of sites treated according to therapy modalities C and D (antibiotics and/or surgery) during the 10 years was registered. RESULTS: Eighteen implants were removed for biological complications. Antibiotic and/or surgical therapy was performed in 10.7% of cases in PHP, in 27% of cases in moderate PCP and in 47.2% cases in severe PCP, with a statistically significant differences between PHP and severe PCP (P = 0.002). At the final examination, the percentage of implants, with at least one site which presented a PD >=6 mm, was respectively 1.7% for PHP, 15.9% for moderate PCP and 27.2% for severe PCP, with a statistically significant difference between PHP and moderate PCP (P = 0.005) and PHP and severe PCP (P = 0.0001). CONCLUSION: Patients with a history of periodontitis presented a statistically significant higher number of sites which required additional treatment. Therefore, patients with a history of periodontitis should be informed that they are more at risk for peri-implant disease. This underlines the value of the SPT in enhancing long-term outcomes of implant therapy, particularly in subjects affected by periodontitis. Therefore, the approach for multiple preventive dental extractions and implant placement, based on the assumption the implants perform better than teeth, should be followed with extreme caution. PMID- 22092446 TI - The validity of the diagnostic criteria used in chronic exertional compartment syndrome: a systematic review. AB - Chronic exertional compartment syndrome (CECS) of the lower limb is part of a group of overuse lower limb injuries with common presenting features. It is commonly diagnosed by the measurement of raised intramuscular pressures in the lower limb. The pathophysiology of the condition is poorly understood, and the criteria used to make the diagnosis are based on small sample sizes of symptomatic patients. We carried out a systematic review to compare intramuscular pressures in the anterior compartment of healthy subjects with commonly used criteria for CECS. Thirty-eight studies were included. With the exception of relaxation pressure, the current criteria for diagnosing CECS, considered to be the gold standard, overlap the range found in normal healthy subjects. Several studies reported mean pressures that would prompt a positive diagnosis for CECS, despite none of the subjects reporting any symptoms. The intramuscular pressure at all time points has also shown to vary in relation to a number of other factors other than the presence of CECS. Taken together, these data have major implications on the ability to use these published criteria for diagnosis and question the underlying pathophysiology. Clinicians are recommended to use protocol-specific upper confidence limits to guide the diagnosis following a failed conservative management. PMID- 22092447 TI - Beliefs associated with Mexican immigrant families' practice of la cuarentena during postpartum recovery. AB - OBJECTIVE: To examine underlying beliefs that motivate the observed behaviors of la cuarentena, which refers to the 40 days (6 weeks) of postpartum recovery observed by Mexican immigrant women in the United States. DESIGN: Qualitative/descriptive. PARTICIPANTS/SETTING: Forty Spanish speaking individuals from 19 different Mexican immigrant families in Colorado were visited in their homes during pregnancy and the postpartum period. METHODS: Ethnographic methods for this study focused on participant observation and interviews during traditional observance of la cuarentena. Mothers, their partners, and caregivers were interviewed in their homes in a series of four visits. RESULTS: Families described perceptions of the body as "open" and vulnerable to drafts or aire. Women reported that the cultural traditions of la cuarentena will "close" the body, and this was seen as the central purpose of postpartum recovery. Immigrant women reported that they hide their traditions in health care settings, recognizing that many providers don't understand or trivialize their beliefs and customs. A lack of awareness of la cuarentena among health care providers is a barrier to many women seeking professional care. CONCLUSIONS: Understanding the underlying fears associated with la cuarentena will assist nurses and clinicians in supporting immigrant families during postpartum recovery. Support from health care providers is particularly important given the occasional lack of family social support for immigrant women after they give birth. PMID- 22092448 TI - NTrap in prevention of stone migration during ureteroscopic lithotripsy for proximal ureteral stones: a meta-analysis. AB - PURPOSE: To evaluate the effectiveness of NTrap in the prevention of stone migration during ureteroscopic lithotripsy for proximal ureteral stones. METHODS: Eligible studies were identified from electronic databases (PubMed, Embase, the Cochrane Library, ISI - Science Citation Index, and Chinese biomedicine literature database). The database search, quality assessment, and data extraction were independently performed by two reviewers. Our primary outcomes were the stone-free (SF) and incidence of stone migration. Secondary outcomes were operative time and the rate of auxiliary procedures. The outcomes were explored by using Review Manager 5.0. Sensitivity analysis was performed to explore the influence of low-quality studies. RESULTS: Two randomized controlled trials and one case-control study including 456 patients met the inclusion criteria. Meta-analysis of extractable data showed that patients who underwent ureteroscopic lithotripsy with the use of the NTrap demonstrated a significant advantage over without the use of the NTrap in terms of the stone-free rate (odds ratio [OR]=3.08, 95% confidence interval [CI] [1.45-6.53], P=0.003); the incidence of stone migration was significantly lower in NTrap treatment than without NTrap (OR=0.23, 95% CI: 0.10-0.53, P=0.0006, while there was no significant difference in operative time between NTrap and control (mean difference=-3.25, 95% CI: -16.11-9.62, P=0.62). Our pooled meta-analysis showed that the incidence of auxiliary shockwave lithotripsy was significantly lower in NTrap treatment than control (OR=0.29, 95% CI: 0.12-0.70, P=0.006). CONCLUSION: The results of this meta-analysis suggested that the NTrap stone occlusion device is efficient at preventing stone retropulsion during ureteroscopic lithotripsy of proximal ureteral calculi. The findings of this review highlight the need for more efficient performance of higher quality, more rigorous, large sample, long term randomized controlled trials where outcomes are detailed in description. PMID- 22092449 TI - Nonfinancial barriers and access to care for U.S. adults. AB - OBJECTIVE: To identify prevalences and predictors of nonfinancial barriers that lead to unmet need or delayed care among U.S. adults. DATA SOURCE: 2007 Health Tracking Household Survey. STUDY DESIGN: Reasons for unmet need or delayed care in the previous 12 months were assigned to one of five dimensions in the Penchansky and Thomas model of access to care. Prevalences of barriers in each nonfinancial dimension were estimated for all adults and for adults with affordability barriers. Multivariable logistic regression models were used to estimate associations between individual, household, and insurance characteristics and barriers in each access dimension. PRINCIPAL FINDINGS: Eighteen percent of U.S. adults experienced affordability barriers and 21 percent experienced nonfinancial barriers that led to unmet need or delayed care. Two thirds of adults with affordability barriers also reported nonfinancial barriers. Young adults, women, individuals with lower incomes, parents, and persons with at least one chronic illness had higher adjusted prevalences of nonfinancial barriers. CONCLUSIONS: Nonfinancial barriers are common reasons for unmet need or delayed care among U.S. adults and frequently coincide with affordability barriers. Failure to address nonfinancial barriers may limit the impact of policies that seek to expand access by improving the affordability of health care. PMID- 22092451 TI - A new method for evaluating postacne scarring. PMID- 22092452 TI - Predictors of actual turnover in a national sample of newly licensed registered nurses employed in hospitals. AB - AIM: This paper is a report of a study of factors that affect turnover of newly licensed registered nurses in United States hospitals. BACKGROUND: There is a large body of research related to nursing retention; however, there is little information specific to newly licensed registered nurse turnover. Incidence rates of turnover among new nurses are unknown because most turnover data are not from nationally representative samples of nurses. METHOD: This study used a longitudinal panel design to obtain data from 1653 registered nurses who were recently licensed by examination for the first time. We mailed surveys to a nationally representative sample of hospital registered nurses 1 year apart. The analytic sample consisted of 1653 nurses who responded to both survey mailings in January of 2006 and 2007. RESULTS: Full-time employment and more sprains and strains (including back injuries) result in more turnover. Higher intent to stay and hours of voluntary overtime and more than one job for pay reduces turnover. When we omitted intent to stay from the probit model, less job satisfaction and organizational commitment led to more turnover, confirming their importance to turnover. Magnet Recognition Award((r)) hospitals and several other work attributes had no effect on turnover. CONCLUSION: Turnover problems are complex, which means that there is no one solution to decreasing turnover. Multiple points of intervention exist. One specific approach that may improve turnover rates is hospital policies that reduce strains and sprains. PMID- 22092453 TI - Stabilization of juxta-physeal distal tibial and fibular fractures in a juvenile tiger using a hybrid circular-linear external fixator. AB - OBJECTIVE: To report stabilization of closed, comminuted distal metaphyseal transverse fractures of the left tibia and fibula in a tiger using a hybrid circular-linear external skeletal fixator. STUDY DESIGN: Clinical report. ANIMAL: Juvenile tiger (15 months, 90 kg). METHODS: From imaging studies, the tiger had comminuted distal metaphyseal transverse fractures of the left tibia and fibula, with mild caudolateral displacement and moderate compression. Multiple fissures extended from the fractures through the distal metaphyses, extending toward, but not involving the distal tibial and fibular physes. A hybrid circular-linear external skeletal fixator was applied by closed reduction, to stabilize the fractures. RESULTS: The fractures healed and the fixator was removed 5 weeks after stabilization. Limb length and alignment were similar to the normal contralateral limb at hospital discharge, 8 weeks after surgery. Two weeks later, the tiger had fractures of the right tibia and fibula and was euthanatized. Necropsy confirmed pathologic fractures ascribed to copper deficiency. CONCLUSION: Closed application of the hybrid construct provided sufficient stability to allow this 90 kg tiger's juxta-articular fractures to heal with minimal complications and without disrupting growth from the adjacent physes. PMID- 22092450 TI - Distinct commensal bacteria associated with ingesta and mucosal epithelium in the gastrointestinal tracts of calves and chickens. AB - The primary aim of this study was to determine whether distinct gastrointestinal tract (GIT) microbial communities are established within ingesta and on mucosal surfaces of dairy calves and chickens to evaluate whether the principle of microbial segregation is of broad biological significance. Multivariate analysis of the predominant bacterial PCR-denaturing gradient gel electrophoresis profiles and estimated bacterial populations were compared in rumen, jejunum, ileum, cecum, and colon ingesta and matching mucosal tissues. Samples collected from 3 week old (n = 8) and 6-month old (n = 8) calves revealed that the predominant mucosa-associated bacteria were distinct from those inhabiting ingesta, and bacterial diversity varied significantly among the GIT regions. The estimated bacterial populations displayed significant regional differences for bovine mucosal (P = 0.05) and for ingesta (P = 0.03) only at 6 months of age. This indicates an established segregation of the enteric bacterial population throughout the GIT in weaned calves. Analysis of ileal and cecal bacterial profiles in chickens confirmed that the segregation of commensal bacteria between ingesta and the mucosal tissue was a common biological phenomenon. Our study provides some fundamental understanding of the impact of sample type (mucosa vs. ingesta), region, and host age on commensal bacterial establishment and segregation throughout the GIT. PMID- 22092454 TI - Poor relevance of a lymphocyte proliferation assay in lamotrigine-induced Stevens Johnson syndrome or toxic epidermal necrolysis. AB - BACKGROUND: Prior use of 'lymphocyte transformation test' (LTT) in Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) provided conflicting results, possibly dependent on sampling dates (acute vs. late). OBJECTIVE: Evaluation of LTT in patients with SJS or TEN who reacted to lamotrigine (LTG). In a small subgroup we explored the possible role of regulatory T cells (T-reg). METHODS: Acute phase samples (9) and post-recovery samples (14) from cases of SJS or TEN to LTG were provided by the RegiSCAR-study group. Controls were persons never exposed to LTG (12), patients exposed without reaction (6), and patients who developed a mild eruption to LTG (6). LTT was performed by measuring (3) H thymidine incorporation after 3 days of incubation with phytohemmaglutinin, LTG (10 MUg/mL) or medium. Stimulation index >= 2 was considered positive. In 16 cases LTT was redone after depletion of T-reg by fluorescence activated cell sorting. RESULTS: Positive LTT was observed in 3/6 cases of mild eruptions, 1/9 SJS/TEN-cases tested during the acute phase and 3/14 SJS/TEN-cases tested after recovery. We noted a very mild and nonsignificant trend for an increased response after depletion of T-reg in late samples from SJS or TEN patients. CONCLUSIONS AND CLINICAL RELEVANCE: With the largest number of LTT performed in patients with SJS or TEN to a single drug, we confirmed that reactive cells are rarely detected in these reactions. Poor reactivity did not seem related to T-reg. Other in vitro assays than those testing proliferation should be evaluated, before raising the hypothesis that specific cells disappeared by undergoing apoptosis during the reaction. PMID- 22092455 TI - MMP-8 -799 C>T genetic polymorphism is associated with the susceptibility to chronic and aggressive periodontitis in Taiwanese. AB - AIM: Matrix metalloproteinase (MMP)-8 is a protease that degrades numerous extracellular molecules and has been implicated in the pathogenesis of periodontitis. Polymorphism in the MMP-8 could affect the susceptibility to disease. Our aim was to evaluate the association between periodontitis and MMP-8 799 C>T polymorphism. MATERIAL AND METHODS: Genomic DNA was obtained from 361 chronic periodontitis patients (CP), 96 aggressive periodontitis patients (AgP), and 106 periodontally healthy controls (HC). MMP-8 -799 C>T polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of genotypes in diseased groups were similar but were significantly different from those in the HC. Multivariate logistic regression analysis with adjustment for age, gender and smoking indicated that increased risks of AgP and CP were associated with the -799 T allele (in AgP, adjusted OR = 1.99, p = 0.04; in CP, adjusted OR = 1.87, p = 0.007). To avoid the confounded effect of smoking on MMP-8 polymorphism to periodontitis, the analysis was conducted on non-smokers and the associations were significant. CONCLUSIONS: These results suggested that non-smoking Taiwanese with the MMP-8 -799 T allele were associated with the risks of both CP and AgP. Further studies in other ethnic populations are necessary. PMID- 22092456 TI - [Past, present, future in public health nursing]. PMID- 22092457 TI - Smoking cessation counseling for parents during child hospitalization: a national survey of pediatric nurses. AB - OBJECTIVE: Given the central role played by pediatric nurses in intake assessment, discharge planning, and education for families of hospitalized pediatric patients, a child's hospitalization may provide a unique opportunity for counseling parents about smoking. We sought to determine if hospital policies can support nurses in effectively counseling parents about smoking. DESIGN AND SAMPLE: We conducted a national survey of pediatric staff nurses and administrators/educators who were members of the Society of Pediatric Nurses in 2008 (n=888) to explore counseling practices for tobacco control. MEASURES: Questionnaires included data on demographics, personal and work environment characteristics, hospital policy characteristics, work attitudes and barriers and the main outcome--5As for smoking cessation counseling--Ask, Advise, Assess, Assist, and Arrange. RESULTS: Overall, routine screening for household smokers was most common (43%), followed by advice to quit (25%), assessing willingness to quit (19%), assisting with a quit plan (6%), and arranging follow-up contact (3%). Nurses working in hospitals with admission assessments specifically asking about household members who smoke were 7 times more likely than those without such assessments to routinely ask about smoking (OR: 7.2, 95% CI: 4.9-10.5). CONCLUSION: Future research should test the efficacy of developing comprehensive hospital-wide policies to deliver smoking cessation for parents during a child's hospitalization. PMID- 22092458 TI - Racial and ethnic disparities in human papillomavirus awareness and vaccination among young adult women. AB - OBJECTIVE: To examine racial and ethnic disparities in human papillomavirus (HPV) awareness and vaccination among young adult females aged 18-24 years. DESIGN AND SAMPLE: Descriptive correlational study. One thousand nineteen women aged 18-24 years who self-identified as Hispanic, non-Hispanic Black, or non-Hispanic White. MEASURES: Descriptive and multivariate logistic regression analyses using data from the 2007-2008 National Survey of Family Growth. RESULTS: Approximately 90% of non-Hispanic White women, 80% of non-Hispanic Black women, and 56-60% of Hispanic women reported an awareness of HPV infection and vaccination, and yet, vaccine receipt across racial and ethnic groups was 23%, 8%, and 6%, respectively. In multivariate analyses, Hispanic and non-Hispanic Black women were less aware than non-Hispanic White women of HPV infection (OR=0.10, 95% CI=0.05, 0.19; OR=0.23, 95% CI=0.13, 0.40) and vaccination (OR=0.13, 95% CI=0.07, 0.27; OR=0.27, 95% CI=0.14, 0.52) and also less likely to report vaccine receipt (OR=0.44, 95% CI=0.21, 0.90; OR=0.16, 95% CI=0.07, 0.35). CONCLUSIONS: Despite moderate to high levels of awareness, HPV vaccination rates were low among this national population of young adult women. Continued surveillance is imperative to monitor vaccine uptake, including racial and ethnic disparities. Further research exploring HPV knowledge and vaccination barriers across diverse cultural groups is needed to inform the development of more effective public health interventions. PMID- 22092459 TI - Intention to smoke tobacco using a waterpipe among students in a southeastern U.S. College. AB - OBJECTIVE: Guided by the Theory of Reasoned Action, this study examined the association of behavioral beliefs, attitudes, normative beliefs, and subjective norms with waterpipe tobacco smoking intention in college students. DESIGN AND SAMPLE: A cross-sectional design was used. A Web-based survey was sent to a random sample of 1,000 undergraduate students from a public institution in the southeast to recruit participants. MEASURES: The Theory of Reasoned Action Waterpipe Questionnaire, a modified version of the Fishbein-Ajzen-Hanson Questionnaire, was used to capture modal constructs of the Theory of Reasoned Action related to waterpipe use. Cronbach's alpha coefficients for the scales of the Theory of Reasoned Action Waterpipe Questionnaire ranged from .76 to .95. RESULTS: Of the sample (n=223), 13.5% currently smoked a waterpipe and 61% had ever done so. Using multiple regression, attitudes, behavioral beliefs, and subjective norms were associated with intention to smoke a waterpipe in the next 3 months and collectively explained 35% of the variance in intention. The full model, which included all the constructs of the Theory of Reasoned Action, demographic variables, and tobacco use variables, explained 83% of the variance in intention to smoke a waterpipe in the next 3 months. CONCLUSIONS: This study provides valuable information that may be used to target students at risk for waterpipe smoking and serves as a starting point in developing theoretically driven interventions to prevent waterpipe smoking. PMID- 22092460 TI - Lifestyle physical activity behavior of Korean American dry cleaner couples. AB - OBJECTIVE: The purposes of this study were to: (1) describe and compare lifestyle physical activity (leisure-time physical activity [LTPA], household physical activity [HPA], and occupational physical activity [OPA]), using both self-report and an objective measure of step counts, in self-employed Korean American married couples working together at dry cleaners, and (2) examine the relationship between self-report and objective measures of physical activity. DESIGN AND SAMPLE: 70 couples participated in this cross-sectional, descriptive, face-to face interview survey. MEASURES: 2 self-reports (28-item Community Healthy Activities Model Program for Seniors Physical Activity Questionnaire and Tecumseh Occupational Physical Activity Questionnaire) and 1 objective measure (New Lifestyles-800 pedometer) were used. RESULTS: The husbands spent significantly more time than their wives in moderate- to vigorous-intensity LTPA (207 vs. 122 min/week) and OPA (2,585 vs. 1,065 min/week). Most couples (91%) met recommended levels of physical activity based on their OPA. Pedometer steps correlated significantly only with LTPA. CONCLUSIONS: Study findings suggest that to increase physical activity in Korean American couples who work in a small business, moderate-intensity lifestyle physical activity interventions across LTPA, HPA, and OPA will be more successful than traditional leisure-time interventions. In addition, results suggest that there is a need for interventions that target both members of the married couple. PMID- 22092461 TI - Benefits, barriers, sources of influence, and prostate cancer screening among rural men. AB - OBJECTIVE: The objective of this study was to explore 3 research questions: (1) What are the perceived benefits of screening for prostate cancer (PC)? (2) What are the perceived barriers to screening for PC? and (3) Is there an association with perceived benefits or perceived barriers and participants' reported source of influence related to prostate cancer screening (PCS) decisions? DESIGN AND SAMPLE: A nonexperimental exploratory design was used for the study. Sample included 94 rural-dwelling male participants aged 40 and older. MEASURES: The instruments used included an adapted version of Champion's (1999) revised Health Belief Model scale and a researcher-developed demographic and PCS patterns form. RESULTS: Both benefits and barriers were significantly associated with PCS and sources of influence. Health care providers and family were highly reported, at 81.8% and 59.5%, respectively, as sources of influence regarding PCS decisions. CONCLUSIONS: In this primarily African American sample, significant barriers to PCS among rural men were indentifed. PC health education may need to include family, whom study participants highly reported as a source of influence regarding their PCS decisions. PMID- 22092462 TI - Empowerment and commitment perceptions of community/public health nurses and their tenure intention. AB - OBJECTIVE: A descriptive, nonexperimental study of community/public health nurses' (C/PHN) perceptions of their work and their workplace was conducted for the purpose of identifying factors that may affect tenure intention and, by extension, health care delivery, at a time when nursing workforce capacity is in crisis, a subject not studied well among the C/PHN workforce. It was thought that findings would potentially contribute to decisions about curriculum development, hiring practices, and work design by nurse educators, leaders, and administrators. Spreitzer's Theory of Structural and Psychological Empowerment and Meyer and Allen's Commitment theory were utilized together as a framework. DESIGN AND SAMPLE: A paper-pen survey was mailed to 688 C/PHNs in 10 states seeking national accreditation serving in community-oriented and population focused roles and selected randomly in local health departments with a census of 10 or more eligible nurses. The return of 478 completed surveys yielded a response rate of 76%. MEASURES: Data were examined with descriptive statistics, correlation, and multiple logistic regression methods. RESULTS: Results revealed 1/3 of C/PHNs were in some way considering leaving the job in spite of significant relationships among empowerment factors and between empowerment and commitment factors. CONCLUSIONS: These data beg for a clearer understanding of C/PHNs' perceptions of empowerment and the reasons for intent to leave. PMID- 22092463 TI - Vaccination competence of public health nurses. AB - OBJECTIVE: The purpose of this study was to assess the vaccination competence of Finnish public health nurses. DESIGN AND SAMPLE: A survey design was used. Participants (n=405) were public health nurses working in health centers in Finland. MEASURES: The data were collected using a structured instrument and were analyzed by SAS. RESULTS: The mean of self-assessment was 8.3 and the proportion percentage of correct answers in the knowledge test was 83 %. According to the self-assessment, public health nurses felt they were most competent in achieving the desired outcomes of vaccination implementation and poorest in their qualities as vaccinators. In the knowledge test, the public health nurses were familiar with vaccination recommendations and common contraindications, but showed room for improvement in managing an anaphylactic reaction, aseptic practices, and knowing the names of vaccines. There was a statistically significant link between the results on the self-assessment and the knowledge test. CONCLUSIONS: Further training should be organized in the areas where knowledge was lacking. It would be useful to further investigate differences in competence between public health nurses working different sectors. These results could be utilized in education, clinical nursing practice, administration and research. This study demonstrated that vaccination competence can be measured by means of the structured instrument. PMID- 22092464 TI - A win-win partnership between academia and public health practice. AB - Partnerships are fundamental to successful public health practice, and collaborations between academia and public health practice, as recommended by the Institute of Medicine and the Council on Linkages between academia and public health practice, are vital to ensuring a competent public health workforce. During times of economic crisis, graduate public health nursing students with clinical expertise, people and communication skills, and critical thinking capabilities are uniquely positioned to bridge the gap between academia and public health practice. In 2009, 5 registered nurses enrolled in a master of science in nursing program with a focus on public health partnered with public health professionals from the state Department of Public Health to conduct an active surveillance study to understand the increase in vancomycin-resistant enterococci incidences that occurred since 2005. The purpose of this paper is to describe the successes and challenges of the collaboration to provide an insight for those who wish to build similar collaborations. Even in light of the challenges that occurred during this collaboration, faculty should strongly consider developing partnerships with public health practice in order to contribute to important public health surveillance and other functions, and to provide relevant experiences for students. PMID- 22092465 TI - Designing a health behavior change program for dissemination to underserved pregnant women. AB - OBJECTIVES: The paper describes the formative research conducted toward developing a health behavior change program for underserved pregnant women. It is provided as an example to guide researchers, academics, and practitioners on how to incorporate dissemination in all aspects of project planning and implementation. DESIGN AND SAMPLE: A series of formative research was conducted, including an advisory council, expert interviews, 6 focus groups and 5 usability interviews with the target population (n=53), key informant interviews, expert reviews of the pilot program, and a pilot test (n=87). A total of 140 underserved pregnant women were recruited from Community Health Center Inc. in Connecticut. RESULTS: The extensive formative research served to lay the foundation for the development of a healthy pregnancy behavior change program. The pilot test exemplified the feasibility and acceptability of the program. CONCLUSION: Successful adoption of interventions depends upon strong formative research, participatory research methods, interdisciplinary collaboration, and a commitment to dissemination from project inception. The development of the intervention discussed serves as a useful and practical example for others working in health care and behavioral medicine to improve the overall health and well-being of the underserved. PMID- 22092467 TI - Public health nursing-indispensible and economical for everyone if organized. AB - In August 1930, the editors of the original Public Health Nursing published an article derived from a speech made by Dr. Haven Emerson, then professor of public health administration at Columbia University, on the topic of the distribution and use of public health nurses. The speech was made before an audience of lay board members from hospitals and public health nursing organizations in Chicago, February 17, 1930. Emerson reported the results of a data analysis in which the numbers and credentials of public health nurses in 24 cities across the United States were reported. Excerpts from this report and Dr. Emerson's conclusions are powerful reminders that while there were issues of labor supply and distribution, the power of nurses to effect social transformation was central to the role as conceived by those administering public health services. PMID- 22092466 TI - Childhood bullying: a review of constructs, concepts, and nursing implications. AB - Bullying among children as a pervasive problem has been increasingly recognized as an important public health issue. However, while much attention has been given to understanding the impact of bullying on victims, it is equally important to examine predictors of bullying and potential outcomes for bullies themselves. The current literature on bullying lacks consensus on a utilizable definition of bullying in research, which can vary by theoretical framework. In an attempt to bridge the gaps in the literature, this article will provide a review of the state of the science on bullying among children, including the major theoretical constructs of bullying and their respective viewpoints on predictors and correlates of bullying. A secondary aim of this article is to summarize empirical evidence for predictors of bullying and victimization, which can provide strategies for intervention and prevention by public health nursing professionals. By calling attention to the variability in the bullying literature and the limitations of current evidence available, researchers can better address methodological gaps and effectively move toward developing studies to inform nursing treatment programs and enhance public health initiatives that reduce violence in school settings. PMID- 22092469 TI - Cancer stem-like cells in adenoid cystic carcinoma of salivary glands: relationship with morphogenesis of histological variants. AB - BACKGROUND: Adenoid cystic carcinoma (AdCC) is a common malignant salivary gland tumor. AdCC is histologically characterized as having cribriform, tubular and solid patterns, and production of excess extracellular matrix (ECM). Cancer stem cells (CSCs) are defined cells within a tumor that possess the capacity to self renew and to induce the heterogeneous lineages of cancer cells that comprise the tumor. METHODS: To examine the morphogenetic relationship between CSCs and the growth patterns in AdCC, we employed formalin-fixed and paraffin-embedded 26 cases of AdCC and immunohistochemically clarified the distribution of CSCs using CD133 and CD44 antibodies. RESULTS: CD133- or CD44-positive cancer stem (CS)-like cells were scattered in the pseudocyst-lining area of cribriform patterns having a Swiss cheese-like appearance. However, based on the further overproduction of ECM, CS-like cells accumulate in thin epithelial cords or trabecular arrangements. These CS-like cell aggregations are considered to form two cell layered tubular patterns. Moreover, proliferation of outer cells in tubular patterns leads to cribriform patterns or solid patterns in the presence of excess ECM production or a lack of ECM overproduction, respectively. CS-like cells in AdCC were frequently located at the border areas adjacent to ECM, with exception of some cribriform and solid variants. CONCLUSION: It is suggested that CSCs included in CD133- or CD44-positive cells play an important role in morphogenesis of salivary AdCC, especially in transition among the histological growth patterns. ECM is well known as a component of the CSC microenvironment, and ECM may regulate morphogenesis of AdCC through the stimulation of CSCs. PMID- 22092470 TI - Alveolar process preservation at implants installed immediately into extraction sockets using deproteinized bovine bone mineral - an experimental study in dogs. AB - AIM: To evaluate the soft tissue and the dimensional changes of the alveolar bony crest at sites where deproteinized bovine bone mineral (DBBM) particles, concomitantly with the placement of a collagen membrane, were used at implants installed into sockets immediately after tooth extraction. MATERIAL AND METHODS: The pulp tissue of the mesial roots of (3) P(3) was removed in six Labrador dogs, and the root canals were filled. Flaps were elevated bilaterally, the premolars hemi-sectioned, and the distal roots removed. Recipient sites were prepared in the distal alveolus, and implants were placed. At the test sites, DBBM particles were placed in the residual marginal defects concomitantly with the placement of a collagen membrane. No treatment augmentation was performed at the control sites. A non-submerged healing was allowed. Impressions were obtained at baseline and at the time of sacrifice performed 4 months after surgery. The cast models obtained were analyzed using an optical system to evaluate dimensional variations. Block sections of the implant sites were obtained for histological processing and soft tissue assessments. RESULTS: After 4 months of healing, no differences in soft tissue dimensions were found between the test and control sites based on the histological assessments. The location of the soft tissue at the buccal aspect was, however, more coronal at the test compared with the control sites (1.8 +/- 0.8 and 0.9 +/- 0.8 mm, respectively). At the three dimensional evaluation, the margin of the soft tissues at the buccal aspect appeared to be located more apically and lingually. The vertical dislocation was 1 +/- 0.6 and 2.7 +/- 0.5 mm at the test and control sites, respectively. The area of the buccal shrinkage of the alveolar crest was significantly smaller at the test sites (5.9 +/- 2.4 mm(2) ) compared with the control sites (11.5 +/- 1.7 mm(2) ). CONCLUSION: The use of DBBM particles concomitantly with the application of a collagen membrane used at implants placed into sockets immediately after tooth extraction contributed to the preservation of the alveolar process. PMID- 22092471 TI - Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. AB - AIMS: Infection may be a rheumatoid arthritis (RA) risk factor. We examined whether signs of periodontal infection were associated with RA development in the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. MATERIAL AND METHODS: In 1971-1974, 9702 men and women aged 25 74 were enrolled and surveyed longitudinally (1982, 1986, 1987, 1992). Periodontal infection was defined by baseline tooth loss or clinical evidence of periodontal disease. Baseline (n = 138) and incident (n = 433) RA cases were defined via self-report physician diagnosis, joint pain/swelling, ICD-9 codes (714.0-714.9), death certificates and/or RA hospitalization. RESULTS: Adjusted odds ratios (ORs) (95% CI) for prevalent RA in gingivitis and periodontitis (versus healthy) were 1.09 (0.57, 2.10) and 1.85 (0.95, 3.63); incident RA ORs were 1.32 (0.85, 2.06) and 1.00 (0.68, 1.48). The ORs for prevalent RA among participants missing 5-8, 9-14, 15-31 or 32 teeth (versus 0-4 teeth) were 1.74 (1.03, 2.95), 1.82 (0.81, 4.10), 1.45 (0.62, 3.41) and 1.30 (0.48, 3.53); ORs for incident RA were 1.12 (0.77, 1.64), 1.67 (1.12, 2.48), 1.40 (0.85, 2.33) and 1.22 (0.75, 2.00). Dose-responsiveness was enhanced among never smokers. The rate of death or loss-to-follow-up after 1982 was two- to fourfold higher among participants with periodontitis or missing >=9 teeth (versus healthy participants). CONCLUSIONS: Although participants with periodontal disease or >=5 missing teeth experienced higher odds of prevalent/incident RA, most ORs were non statistically significant and lacked dose-responsiveness. Differential RA ascertainment bias complicated the interpretation of these data. PMID- 22092472 TI - Periodontitis is associated with angiographically verified coronary artery disease. AB - INTRODUCTION: We investigated the association of periodontitis and severity of coronary artery disease (CAD) as verified using coronary angiography. MATERIAL AND METHODS: Participants were recruited among those attending coronary angiography at Helsinki University Central Hospital, Finland, in 2007 and 2008. Detailed clinical periodontal examination [number of teeth, bleeding on probing, periodontal probing depth (PPD)] and oral panoramic radiographs [alveolar bone loss (ABL), angular bone defects] were performed. RESULTS: Of 506 patients, 123 (24.3%) had no significant CAD, whereas 184 (36.4%) had stable CAD and 169 (33.4%) acute coronary syndrome (ACS). Both stable CAD and ACS were associated with 8-17 missing teeth with ORs 4.33 (1.61-11.7, p = 0.020) and 5.24 (1.90-14.5, p = 0.014), and more than seven teeth with PPD >=6 mm with ORs 2.44 (1.01-6.07, p = 0.049) and 2.75 (1.16-6.53, p = 0.022) respectively. Severe ABL was associated with ACS with an OR 5.39 (1.23-23.6, p = 0.025). Number of stenosed arteries was linearly associated with ABL (p for trend <0.001), number of missing teeth (p < 0.001), and pockets with probing depth >=6 mm (p = 0.033). CONCLUSIONS: Compared with patients with no significant stenosis, poor periodontal health including missing teeth, periodontal inflammation, and bone loss is associated with angiographically verified coronary artery narrowing in patients with stable CAD or ACS. PMID- 22092473 TI - Stage of hepatocellular carcinoma is associated with periodontitis. AB - AIM: Periodontitis induces overproduction of reactive oxygen species (ROS). This state increases circulating ROS levels and may affect hepatocellular carcinoma (HCC). The Japan Integrated Stage (JIS) score is a novel staging system for HCC. The objective of the present study was to compare JIS scores in HCC patients with and without periodontitis. MATERIAL AND METHODS: We recruited 64 HCC patients comprising 31 chronic periodontitis subjects (HCC + P) and 33 periodontally healthy controls (HCC + H). Their JIS scores were recorded. Serum levels of reactive oxygen metabolites (ROM) from HCC + P, HCC + H and healthy age- and gender-matched subjects with healthy gingiva (control, n = 15) were also assessed for circulating ROS levels. RESULTS: The HCC + P and HCC + H groups had similar body mass index, habitual drinking and tobacco exposure data. The HCC + P group showed higher JIS scores than the HCC + H group (p = 0.027). Both the HCC + P and HCC + H groups had higher serum levels of ROM than controls (p < 0.001), while serum levels of ROM in the HCC + P group were a further 25.8% higher than those in the HCC + H group (p < 0.001). CONCLUSION: HCC patients with periodontitis had higher JIS score and circulating ROS level than HCC patients without periodontitis. PMID- 22092474 TI - Receptor activator of nuclear factor kappa B ligand antagonists inhibit tissue inflammation and bone loss in experimental periodontitis. AB - AIM: The purpose of this study was to assess the role of anti-bone resorptive agents and an anti-inflammatory compound in murine Porphyromonas gingivalis (P. gingivalis)-induced periodontitis. MATERIAL AND METHODS: Six randomly assigned groups were administered vehicle (saline, control) (n = 6), P. gingivalis infection only (untreated) (n = 6), human-Fc (n = 4), Kavain (n = 6), OPG-Fc (n = 6) and Receptor activator of nuclear factor-kappa B (RANK)-Fc (n = 6) intraperitoneally at day 0, 3 and 7. Animals were euthanized on day 10 and subjected to comprehensive histomorphometric analysis. To capture the progress of inflammation, serum samples were collected at days 0, 3, 7 and 10 for levels of pro-inflammatory cytokines. RESULTS: Compared with control group, OPG-Fc, RANK-Fc and Kavain treatment showed significant bone loss reduction with OPG-Fc performing better than RANK-Fc or Kavain. Epithelial down-growth showed significant reduction in treatment groups with OPG-Fc performing better than RANK Fc or Kavain. Finally, Kavain, OPG-Fc and RANK-Fc-treated mice displayed reduced inflammatory cell counts and cytokine expression particularly at day 7 postinfection. CONCLUSIONS: RANKL antagonists and Kavain effectively reduced alveolar bone loss in P. gingivalis-induced periodontitis in our mice model. Compared with RANK-Fc, Kavain-treated animals showed milder improvement of bone and connective tissue inflammation. Therapeutic implications in the prevention of periodontal bone loss are discussed. PMID- 22092475 TI - Multiple applications of flurbiprofen and chlorhexidine chips in patients with chronic periodontitis: a randomized, double blind, parallel, 2-arms clinical trial. AB - AIM: The aim of the present randomized, double blind, parallel, 2-arm clinical study was to examine the safety and efficacy of frequent applications of chlorhexidine chip (CHX) and flurbiprofen chip (FBP) in patients with chronic periodontitis. METHODS: Sixty patients were randomized into CHX and FBP groups. Following OHI and scaling and root planing (SRP), baseline pocket depth (PD) measurements, gingival recession and bleeding on probing (BOP) were performed and repeated at week 4 and 8. The assigned chip was placed at weeks 0, 1, 2, 3, 5, 7. RESULTS: Mean PD reduction in the CHX group was 2.08 mm (7.17 to 5.09, p < 0.0001). Mean PD reduction in the FBP group was 2.27 mm (6.72 to 4.45, p < 0.0001). Ninety-seven percentage and 95% of these sites exhibited PD reduction >=1 mm, while 38% and 34% of the sites exhibited PD >=3 mm (FBP and CHX, respectively). Clinical attachment level gain (1.66 and 1.95 mm, respectively) was statistically significant (p < 0.0001). Baseline BOP dropped from 98% and 100% to 24% and 30% for the CHX and FBP groups, respectively (p < 0.0001). CONCLUSION: Frequent applications of CHX and FBP chips resulted in a significant improvement in the periodontal condition in these sites. Furthermore studies will be required to compare this new treatment regimen to SRP or SRP with single chip application. PMID- 22092476 TI - A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/beta-TCP for periodontal regeneration. AB - AIM: The primary objective of this study was to clinically and histologically evaluate periodontal wound healing/regeneration following surgical implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a particulate beta-tricalcium phosphate (beta-TCP) carrier rhGDF-5/beta-TCP into periodontal defects in man. MATERIAL & METHODS: Twenty chronic periodontitis patients, each with at least one tooth scheduled for extraction exhibiting a probing depth >=6 mm and an associated intra-bony defect >=4 mm participated in the study upon written informed consent. Subjects (one defect/patient) were randomized to receive open flap debridement (OFD) + rhGDF-5/beta-TCP (n = 10) or OFD alone (control; n = 10). Block biopsies of the defect sites were collected at 6 months post-surgery and prepared for the histological evaluation. Two masked examiners evaluated the deepest aspect of each defect site relative to bone (height/area), periodontal ligament (PDL) and cementum regeneration, and residual beta-TCP. RESULTS: Sites receiving rhGDF-5/beta-TCP showed numerically greater PD reduction (3.7 +/- 1.2 versus 3.1 +/- 1.8 mm; p = 0.26), less gingival recession (0.5 +/- 0.8 versus 1.4 +/- 1.0 mm; p < 0.05) and greater clinical attachment level (CAL) gain (3.2 +/- 1.7 versus 1.7 +/- 2.2 mm; p = 0.14) at the deepest aspect of the defect compared with OFD alone. One biopsy in the rhGDF-5/beta-TCP and four biopsies in the OFD group were deemed as not evaluable. Histologically, bone regeneration height was almost threefold greater for the rhGDF-5/beta-TCP treatment compared with OFD alone (2.19 +/- 1.59 versus 0.81 +/- 1.02 mm; p = 0.08). Similarly an almost twofold increase was observed for PDL (2.16 +/- 1.43 versus 1.23 +/- 1.07 mm; p = 0.26), cementum (2.16 +/- 1.43 versus 1.23 +/- 1.07 mm; p = 0.26) and bone regeneration area (0.74 +/- 0.69 versus 0.32 +/- 0.47 mm(2) ; p = 0.14). Root resorption/ankylosis was not observed. Residual beta-TCP occupied 8.4 +/- 11.5% of the area of interest in biopsies of patients receiving rhGDF-5/beta-TCP. Five biopsies (one rhGDF-5/beta-TCP, four OFD) were deemed unsuitable to allow a meaningful histological or histometrical evaluation. CONCLUSIONS: Descriptive statistics showed greater PD reduction and CAL gain, and greater alveolar bone regeneration and periodontal regeneration at sites that received rhGDF-5/beta-TCP compared to control. However, these differences were not statistically significant. Future studies with larger sample sizes will have to be conducted to verify these findings. PMID- 22092477 TI - Coronally advanced flap adjunct with low intensity laser therapy: a randomized controlled clinical pilot study. AB - AIM: Coronally advanced flap (CAF) technique and its modifications have been proposed in the literature. Low intensity laser therapy (LILT) is shown to increase wound healing. The aim of this split-mouth randomized controlled pilot study was to assess the effects of LILT with respect to root coverage after CAF procedure for the treatment of multiple-recession type defects (MRTD). MATERIAL AND METHODS: Ten patients with symmetrical 74 Miller I and II gingival recessions were included in this study (37 in test, 37 in control group). A diode laser (588 nm) was applied to test sites before and immediately after surgery, and for 5 min. daily 7 days post-operatively. Comparisons of the surgical sites were made with clinical measurements. RESULTS: Statistically significant differences were observed between test and control sites in the gingival recession depth (GRD), gingival recession width (GRW) and width of the keratinized tissue (WKT) and clinical attachment level (CAL) measurements after 1 year (p = 0.014, p = 0.015, p = 0.009 and p = 0.018 respectively). The test group presented greater complete root coverage (n = 7, 70%) compared with the control group (n = 3, 30%) after treatment. CONCLUSION: Within the limitations of this study, the results indicated that LILT may improve the predictability of CAF in multiple recessions. PMID- 22092478 TI - Soft tissue volume augmentation by the use of collagen-based matrices in the dog mandible -- a histological analysis. AB - OBJECTIVES: The aim was to test, whether or not soft tissue volume augmentation with a specifically designed collagen matrix (CM), leads to ridge width gain in chronic ridge defects similar to those obtained by an autogenous subepithelial connective tissue graft (SCTG). MATERIAL AND METHODS: In six dogs, soft tissue volume augmentation was performed by randomly allocating three treatment modalities to chronic ridge defects [CM, SCTG and sham-operated control (Control)]. Dogs were sacrificed at 28 (n = 3) and 84 days (n = 3). Descriptive histology and histomorphometric measurements were performed on non-decalcified sections. RESULTS: SCTG and CM demonstrated favourable tissue integration, and subsequent re-modelling over 84 days. The overall mean amount of newly formed soft tissue (NMT) plus bone (NB) amounted to 3.8 +/- 1.2 mm (Control), 6.4 +/- 0.9 mm (CM) and 7.2 +/- 1.2 mm (SCTG) at 28 days. At 84 days, the mean NMT plus NB reached 2.4 +/- 0.9 mm (Control), 5.6 +/- 1.5 mm (CM) and 6.0 +/- 2.1 mm (SCTG). Statistically significant differences were observed between CM/SCTG and Control at both time-points (p < 0.05). CONCLUSION: Within the limits of this animal model, the CM performed similar to the SCTG, based on histomorphometric outcomes combining NB and NMT. PMID- 22092479 TI - Cyclic loading of tendon fascicles using a novel fatigue loading system increases interleukin-6 expression by tenocytes. AB - Repetitive strain or 'overuse' is thought to be a major factor contributing to the development of tendinopathy. The aims of our study were to develop a novel cyclic loading system, and use it to investigate the effect of defined loading conditions on the mechanical properties and gene expression of isolated tendon fascicles. Tendon fascicles were dissected from bovine-foot extensors and subjected to cyclic tensile strain (1 Hz) at 30% or 60% of the strain at failure, for 0 h (control), 15 min, 30 min, 1 h, or 5 h. Post loading, a quasi-static test to failure assessed damage. Gene expression at a selected loading regime (1 h at 30% failure strain) was analyzed 6 h post loading by quantitative real-time polymerase chain reaction. Compared with unloaded controls, loading at 30% failure strain took 5 h to lead to a significant decrease in failure stress, whereas loading to 60% led to a significant reduction after 15 min. Loading for 1 h at 30% failure strain did not create significant structural damage, but increased Collagen-1-alpha-chain-1 and interleukin-6 (IL6) expression, suggesting a role of IL6 in tendon adaptation to exercise. Correlating failure properties with fatigue damage provides a method by which changes in gene expression can be associated with different degrees of fatigue damage. PMID- 22092480 TI - Evaluation of peri-implant bone resorption around Straumann Bone Level implants placed in areas reconstructed with autogenous vertical onlay bone grafts. AB - AIM OF THE STUDY: To evaluate the survival and success rate of Straumann Bone Level implants placed in vertically atrophied edentulous jaws previously reconstructed with autogenous onlay bone grafts taken from the calvarium or the mandibular ramus. MATERIALS AND METHODS: From 2007 to 2009, 18 patients presenting with vertical deficits of the edentulous ridges were treated with autogenous cortical bone grafts harvested from the mandibular ramus or the calvarium. Four to seven months afterward, 60 Straumann Bone Level implants were placed in the reconstructed areas. After a further waiting period of 2-3 months, patients were rehabilitated with implant-supported fixed prostheses. Follow-up ranged from 12 to 36 months (mean: 19 months) after the start of prosthetic loading. Graft resorption before implant placement, as well as survival and success rates of implants, were recorded. RESULTS: The mean bone resorption prior to implant placement was 0.18 mm for calvarial grafts and 0.42 mm for ramus grafts. Survival rate was 100% either for implants placed in calvarial grafts or implants placed in ramus grafts, while success rate was 90.3% for implants placed in calvarial grafts, and 93.1% for implants placed in ramus grafts. CONCLUSION: Results from this study seem to demonstrate that implants with a platform switching design may predictably integrate in edentulous areas reconstructed with autogenous bone grafts, with survival rates consistent with those reported in recent literature reviews on the same topic, and also with implants placed in native bone. Conversely, this study was not able to demonstrate that implants with platform-switching design may reduce bone resorption around implants placed in reconstructed areas. PMID- 22092481 TI - Effects of bait age, larval chemical cues and nutrient depletion on colonization by forensically important Calliphorid and Sarcophagid flies. AB - Species colonization patterns on corpses and the frequency of carrion fly oviposition and larviposition are affected by decomposition stage and previous maggot colonization. This study investigated these effects on meat bait colonization by Victorian Diptera of forensic importance. Bait treatments were: 'aged' (aged for 4 days at 22 degrees C, allowing some decomposition); 'nutrient depleted' [aged for 4 days at 22 degrees C with feeding Calliphora vicina (Robineau-Desvoidy) (Diptera: Calliphoridae) larvae]; 'extract' (fresh bait mixed with liquid formed by feeding C. vicina larvae), and 'fresh' (untreated control bait). Statistical analysis (alpha = 0.05) revealed that colonization frequency differed significantly among treatments (Welch's F(3,18.83) = 4.66, P < 0.05). Post hoc tests showed that fresh and extract baits were colonized extensively throughout the experiment with no significant difference, whereas the colonization of nutrient-depleted baits was significantly lower. This suggests that larval digestive enzymes, larval excreta and cuticular hydrocarbons have less effect on colonizing Diptera than the nutritional content of meat. The colonization of aged baits did not differ significantly from that of fresh, extract or nutrient-depleted baits. A further experiment testing 'very aged' (aged for 8 days at 28 degrees C), 'larvae-added' (fresh bait with C. vicina larvae added before placement) and 'fresh' (untreated control) baits revealed that very aged baits were colonized significantly less frequently than either fresh or larvae-added baits (Welch's F(2, 6.17) = 17.40, P < 0.05). PMID- 22092482 TI - Public awareness and attitudes towards cutaneous leishmaniasis in an endemic region in Saudi Arabia. AB - BACKGROUND AND AIMS: One of the priorities in public health policy for the control of Cutaneous Leishmaniasis (CL) is to investigate associations between disease distribution, socio-demographical and environmental risk factors, so that rational prevention and control strategies can be developed. Assessment of baseline awareness of the disease amongst the endemic population would be one of the first steps in this direction. This study aims to provide qualitative information on lay perceptions of CL in an endemic area in Saudi Arabia. We also attempted to correlate these perceptions with associated socio-demographical backgrounds. METHODS: This was a cross-sectional descriptive survey carried out in Al-Hassa, located in the Eastern Province of Saudi Arabia. The study included 1824 participants, age ranging from 15 to 63 years (mean 35.86+/-9.54 years). RESULTS: Over 76% of the studied population recognized the infectious nature of CL. There was also good awareness regarding the clinical features of CL, but the awareness regarding the vector, transmission, risk factors and preventive methods were very poor. Our study demonstrated a significantly higher knowledge score correlated with regard to male gender, higher family income, age and a previous history of CL. CONCLUSION: In our study we found low awareness for important epidemiological aspects like transmission of the disease, risk factors and prevention. Our study provides a baseline to understand and correct deficits in the perceptions and knowledge regarding CL in Saudi Arabia and would provide a template to design interventions. PMID- 22092483 TI - Antibiotics and asthma medication in a large register-based cohort study - confounding, cause and effect. AB - BACKGROUND: An association between asthma and antibiotic usage has been demonstrated, and the issue of reverse causation and confounding by indication is much debated. OBJECTIVE: Our aim was to study the association between different classes of antibiotics and prescription of asthma medication in a register-based cohort of all Swedish children, born between July 2005 and June 2009, ever treated with antibiotics. METHODS: Data on dispensed prescriptions of antibiotics (ATC-codes J01) and asthma medication (ATC-codes R03A-D) were requested from the Prescribed Drug Register. The association between dispensed prescriptions of different classes of antibiotics and asthma medication was analysed with Cox regression and a descriptive sequence symmetry analysis. RESULTS: In total, 211 192 children had received prescriptions of antibiotics. There was a strong association between prescription of antibiotics and prescription of asthma medication. The hazard ratios (HRs) for asthma medication associated with prescription of amoxicillin, penicillin, cephalosporin and macrolides (Gram positive infections) were stronger than HRs associated with prescription of sulphonamides, trimethoprim and quinolones (urinary tract infections) and flucloxacillin (skin and soft tissue infections), e.g. first year HR = 2.27 (95% confidence intervals 2.17-2.37) as compared with HR = 1.04 (0.78-1.40). The HR associated with broad spectrum antibiotics was significantly higher than the narrow spectrum. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that the association between antibiotics and asthma is subject to either reverse causation or confounding by indication due to respiratory tract infections. This implies that careful consideration is required as to whether or not symptoms from the respiratory tract in early childhood should be treated with antibiotics or asthma medication. PMID- 22092484 TI - Effect of vitamin supplementation on lung injury and running performance in a hot, humid, and ozone-polluted environment. AB - In this study, the effect of vitamin C and E supplementation on lung injury and performance of runners were analyzed. Using a randomized, double-blinded, crossover design, nine runners participated in two experimental trials: a 2-week Vitamin trial (vitamin C = 500 mg/day + vitamin E = 100 IU/day) and a 2-week Placebo trial. At the end of each supplementation period the runners performed an 8-km time-trial run in a hot (31 degrees C), humid (70% rh), and ozone-polluted (0.10 ppm O(3)) environmental chamber. Nasal lavage and blood samples were collected pre-, post-, and 6-h post-exercise to assess antioxidant status and CC16 as lung injury marker. Higher plasma (pre- and post-exercise) and nasal lavage (post-exercise) antioxidant concentration were found for the Vitamin trial. Nevertheless, this did not result in performance differences (Vitamin trial: 31:05 min; Placebo trial: 31:54 min; P = 0.075) even though significant positive correlations were found between antioxidant concentration and improvement in time to complete the run. CC16 was higher post-exercise in the Placebo trial (P < 0.01) in both plasma and nasal lavage. These findings suggest that antioxidant supplementation might help to decrease the lung injury response of runners when exercising in adverse conditions, but has little effect on performance. PMID- 22092485 TI - Clinical, histologic and histomorphometric evaluation of socket preservation using a synthetic nanocrystalline hydroxyapatite in comparison with a bovine xenograft: a randomized clinical trial. AB - OBJECTIVES: The aim of this study was to compare a nanocrystalline hydroxyapatite (NCHA), NanoBone((r)) and a deproteinized bovine bone mineral (DBBM), Bio Oss((r)) with a collagen membrane on the horizontal ridge width alterations following tooth extraction, in addition to histologic aspects of the grafted extraction sockets. MATERIAL AND METHODS: In this randomized clinical trial, 28 symmetrical, non-molar, extraction sockets using a split-mouth design in 12 patients (eight women and four men; aged 21-60; mean 44.6 +/- 11.4 years), were randomly selected in the first group to be grafted with DBBM granules covered with a collagen membrane and in the other group grafted with NCHA covered with a collagen membrane. Following extraction horizontal ridge width was measured using caliper and was blindly compared to the dimensions measured prior to implant placement, at the 6- to 8-month follow-up. Subsequently, a 2 * 6 mm trephine core was obtained with aid of acrylic stent and routine histologic preparation was performed on the specimens. RESULTS: The width of the DBBM group decreased from 7.75 +/- 1.55 to 6.68 +/- 1.85 mm (P < 0.05), whereas the width of the NCHA group decreased from 7.36 +/- 1.94 to 6.43 +/- 2.08 mm (P < 0.05). The mean between group difference did not reach statistical significance (P = 0.62). Furthermore, histologic and histomorphometric analyses revealed 28.63 +/- 12.53% vital bone in NCHA group vs. 27.35 +/- 12.39% in DBBM group, and no statistically significant difference between the groups (P = 0.68). CONCLUSION: Socket preservation using either NCHA or DBBM in combination with collagen membrane, results in similar, limited horizontal ridge width alterations following tooth extraction. PMID- 22092486 TI - A 2D MEMS mirror with sidewall electrodes applied for confocal MACROscope imaging. AB - This paper presents microelectromechanical system micromirrors with sidewall electrodes applied for use as a Confocal MACROscope for biomedical imaging. The MACROscope is a fluorescence and brightfield confocal laser scanning microscope with a very large field of view. In this paper, a microelectromechanical system mirror with sidewall electrodes replaces the galvo-scanner and XYZ-stage to improve the confocal MACROscope design and obtain an image. Two micromirror-based optical configurations are developed and tested to optimize the optical design through scanning angle, field of view and numerical aperture improvement. Meanwhile, the scanning frequency and control waveform of the micromirror are tested. Analysing the scan frequency and waveform becomes a key factor to optimize the micromirror-based confocal MACROscope. When the micromirror is integrated into the MACROscope and works at 40 Hz, the micromirror with open-loop control possesses good repeatability, so that the synchronization among the scanner, XYZ-stage and image acquisition can be realized. A laser scanning microscope system based on the micromirror with 2 MUm width torsion bars was built and a 2D image was obtained as well. This work forms the experimental basis for building a practical confocal MACROscope. PMID- 22092487 TI - A genetic discontinuity in root-nodulating bacteria of cultivated pea in the Indian trans-Himalayas. AB - Evolutionary relationships of 120 root-nodulating bacteria isolated from the nodules of Pisum sativum cultivated at 22 different locations of the trans Himalayan valleys of Lahaul and Spiti in the state of Himachal Pradesh of India were studied using 16S rRNA gene PCR-RFLP, ERIC-PCR, sequencing of 16S rRNA, atpD, recA, nodC and nifH genes, carbon-source utilization pattern (BIOLOGTM), and whole-cell fatty acid profiling. The results demonstrated that all isolates belonged to Rhizobium leguminosarum symbiovar viciae (Rlv). Isolates from the two valleys were clearly separated on the basis of ERIC fingerprints, carbon-source utilization pattern, and whole-cell fatty acid methyl esters. Phylogenetic analysis of atpD, recA, nodC and nifH genes revealed a common Rlv sublineage in Spiti valley. Lahaul valley isolates were represented by three sequence types of atpD and recA genes, and four sequence types of nodC and nifH genes. Genotypes from the two valleys were completely distinct, except for two Lahaul isolates that shared nodC and nifH sequences with Spiti isolates but were otherwise more similar to other Lahaul isolates. Isolates from the two highest Spiti valley sites (above 4000 m) had a distinctive whole-cell fatty acid profile. Spiti valley isolates are closely related to Rlv sublineages from Xinjiang and Shanxi provinces in China, while Lahaul valley isolates resemble cosmopolitan strains of the western world. The high mountain pass between these valleys represents a boundary between two distinct microbial populations. PMID- 22092488 TI - Young women's experiences living with polycystic ovary syndrome. AB - OBJECTIVE: To explore the psychosocial effects of living with polycystic ovary syndrome (PCOS) through the experiences of young women diagnosed with this endocrine disorder. DESIGN: A qualitative, phenomenological methodology was used. Data were obtained through personal, semistructured interviews. SETTING: College campuses in New England. PARTICIPANTS: A purposive sample of 12 young women with PCOS age 18 to 23 years. RESULTS: The following themes emerged from analysis of participants' responses: concerns for older self, feeling physically inferior, coping with symptoms, patient-provider relationship, seeking useable information and support, and coming to terms with a chronic condition. CONCLUSIONS: Participants in this study faced numerous physical, social, and emotional challenges on a daily basis. As these young women gathered information relevant to their needs, sought and received social support, and maintained their daily routines to improve their health and appearance, they came to terms with this chronic condition. Based on participants' relayed experiences, it became evident that a need exists for health care practitioners to include psychosocial support in a comprehensive holistic plan for the treatment of PCOS in adolescents and young women in their early twenties. PMID- 22092489 TI - What drives the distribution of the bloom-forming cyanobacteria Planktothrix agardhii and Cylindrospermopsis raciborskii? AB - The cyanobacteria Planktothrix agardhii and Cylindrospermopsis raciborskii are bloom-forming species common in eutrophic freshwaters. These filamentous species share certain physiological traits which imply that they might flourish under similar environmental conditions. We compared the distribution of the two species in a large database (940 samples) covering different climatic regions and the Northern and Southern hemispheres, and carried out laboratory experiments to compare their morphological and physiological responses. The environmental ranges of the two species overlapped with respect to temperature, light and total phosphorus (TP); however, they responded differently to environmental gradients; C. raciborskii biovolume changed gradually while P. agardhii shifted sharply from being highly dominated to a rare component of the phytoplankton. As expected, P. agardhii dominates the phytoplankton with high TP and low light availability conditions. Contrary to predictions, C. raciborskii succeeded in all climates and at temperatures as low as 11 degrees C. Cylindrospermopsis raciborskii had higher phenotypic plasticity than P. agardhii in terms of pigments, individual size and growth rates. We conclude that the phenotypic plasticity of C. raciborskii could explain its ongoing expansion to temperate latitudes and suggest its future predominance under predicted climate-change scenarios. PMID- 22092490 TI - An assay for exogenous sources of purified MurG, enabled by the complementation of Escherichia coli murG(Ts) by the Mycobacterium tuberculosis homologue. AB - The Mycobacterium tuberculosis murG gene, Rv2153, was expressed in Escherichia coli murG(Ts) strain OV58 on a plasmid under the control of the arabinose inducible araBAD promoter. Mycobacterium tuberculosis murG rescued the growth of E. coli murG(Ts) at the nonpermissive temperature: transformants were only obtained in the presence of 0.2% arabinose at 42 degrees C, and their growth rate was dependent on arabinose concentrations. However, no MurG activity was detected in membranes from the transformant grown in arabinose at 42 degrees C, while MraY activity was normal. This observation led to the development of a membrane-based scintillation proximity assay for exogenous sources of MurG. Addition of purified E. coli MurG resulted in the reconstitution of MurG and peptidoglycan synthesis in these membranes. MurG is an attractive target for drug discovery, but assays to measure the activity of purified MurG are challenging. This presents an easy method to measure the activity of exogenous sources of MurG for structure-activity studies of mutant MurG proteins. It can also be used to compare the activity of, or effect of inhibitors on, MurG from other bacterial species. PMID- 22092491 TI - Influence of implants with different sizes and configurations installed immediately into extraction sockets on peri-implant hard and soft tissues: an experimental study in dogs. AB - AIM: To study the influence on the healing of soft and hard peri-implant tissues when implants of different sizes and configurations were installed into sockets immediately after tooth extraction. MATERIAL AND METHODS: Transmucosal cylindrical implants, 3.3 mm in diameter in the control sites, and conical 5 mm in diameter in the test sites, were installed into the distal socket of the fourth mandibular premolars in dogs immediately after tooth extraction. After 4 months, the hard and soft tissue healing was evaluated histologically. RESULTS: All implants were integrated in mineralized mature bone. Both at the test and control sites, the alveolar crest underwent resorption. The buccal bony surface at the implant test sites (conical; 3.8 mm) was more resorbed compared with the control sites (cylindrical; 1.6 mm). The soft tissue dimensions were similar in both groups. However, in relation to the implant shoulder, the peri-implant mucosa was located more apically at the test compared with the control sites. CONCLUSION: The present study confirmed that the distance between the implant surface and the outer contour of the buccal alveolar bony crest influenced the degree of resorption of the buccal bone plate. Consequently, in relation to the implant shoulder, the peri-implant mucosa will be established at a more apical level, if the distance between the implant surface and the outer contour of the alveolar crest is small. PMID- 22092492 TI - Effects of a physical education program on physical activity, fitness, and health in children: the JuvenTUM project. AB - The purpose of the study was to investigate the effects of a school-based prevention program on physical activity, fitness, and obesity. We performed a prospective study in eight Bavarian primary schools (n = 724 children, 8.4 +/- 0.7 years) randomized one to one to either an intervention school (IS, n = 427) or a control school (CS, n = 297). Children in IS attended 10 health-related lessons at school over a period of 1 year. Parents and teachers attended two and three educational health-related lessons, respectively, and also received 10 newsletters on health issues. Daily physical activity (>= 60 min/day), physical fitness (six-item test battery), and anthropometric data were obtained at baseline and after 1 year. Physical activity and physical fitness increased in IS, but it failed to reach significant intervention effects. Nevertheless, a reduction in waist circumference was observed for all children [mean change 1.7 cm; 95% confidence interval (CI) 1.2-2.3; P < 0.001). This effect was more pronounced in overweight children (> 90th percentile, n = 99, mean change 3.2 cm; 95% CI 1.5-4.8; P < 0.001). This easily administered preventative program involving children, parents, and teachers revealed that a generalized approach increasing physical activity will even be favorable in a subgroup of obese children. PMID- 22092494 TI - Prevalence of clinical and subclinical middle ear disease in cats undergoing computed tomographic scans of the head. AB - Three hundred and ten cats that had CT imaging of the head between January 2000 and December 2007 were evaluated retrospectively. Data that were recorded included signalment, presenting complaint, clinical signs, presence of upper respiratory tract disease, and CT findings. One hundred and one cats had evidence of middle ear disease on CT. Thirty-four of the 101 cats (34%) did not have a primary complaint of ear-related disease, clinical signs or physical findings consistent with ear disease, suggesting that the middle ear disease was subclinical. Twenty-seven of the 34 cats (79%) had concurrent nasal disease. Middle ear lesions were chronic in appearance. With the exception of tympanic bulla lysis, CT findings were similar in cats presenting with primary aural disease versus cats with presumptive subclinical middle ear disease. The majority of the cats did not return for treatment of the identified middle ear abnormalities. Subclinical middle ear disease is relatively frequent in cats undergoing CT imaging of the head. Few cats required subsequent treatment for ear disease although follow up was limited. Identification of subclinical middle ear abnormalities on CT should prompt acquisition of a detailed patient history and bilateral otoscopic examination. PMID- 22092493 TI - Swarming motility and the control of master regulators of flagellar biosynthesis. AB - Swarming motility is the movement of bacteria over a solid surface powered by rotating flagella. The expression of flagellar biosynthesis genes is governed by species-specific master regulator transcription factors. Mutations that reduce or enhance master regulator activity have a commensurate effect on swarming motility. Here we review what is known about the proteins that modulate swarming motility and appear to act upstream of the master flagellar regulators in diverse swarming bacteria. We hypothesize that environmental control of the master regulators is important to the swarming phenotype perhaps at the level of controlling flagellar number. PMID- 22092495 TI - Microbial community structure in methane hydrate-bearing sediments of freshwater Lake Baikal. AB - Gas hydrates in marine sediments have been known for many years but recently hydrates were found in the sediments of Lake Baikal, the largest freshwater basin in the world. Marine gas hydrates are associated with complex microbial communities involved in methanogenesis, methane oxidation, sulfate reduction and other biotransformations. However, the contribution of microorganisms to the formation of gas hydrates remains poorly understood. We examined the microbial communities in the hydrate-bearing sediments and water column of Lake Baikal using pyrosequencing of 16S rRNA genes. Aerobic methanotrophic bacteria dominated the water sample collected at the lake floor in the hydrate-bearing site. The shallow sediments were dominated by Archaea. Methanogens of the orders Methanomicrobiales and Methanosarcinales were abundant, whereas representatives of archaeal lineages known to perform anaerobic oxidation of methane, as well as sulfate-reducing bacteria, were not found. Affiliation of archaea to methanogenic rather than methane-oxidizing lineages was supported by analysis of the sequences of the methyl coenzyme M reductase gene. The deeper sediments located at 85-90 cm depth close to the hydrate were dominated by Bacteria, mostly assigned to Chloroflexi, candidate division JS1 and Caldiserica. Overall, our results are consistent with the biological origin of methane hydrates in Lake Baikal. PMID- 22092496 TI - Immunoglobulin E-binding autoantigens: biochemical characterization and clinical relevance. AB - Although immediate-Type I skin reactions to human dander have been described six decades ago, only the recent application of molecular biology to allergology research allowed fast and detailed characterization of IgE-binding autoantigens. These can be functionally subdivided into three classes: (1) self-antigens with sequence homology to environmental allergens belonging to the class of phylogenetically conserved proteins, (2) self-antigens without sequence homology to known environmental allergens, and (3) chemically modified self-antigens deriving from workplace exposure. As environmental allergens, also IgE-binding autoantigens belong to different protein families without common structural features that would explain their IgE-binding capability. Many of the self antigens showing sequence homology to environmental allergens, are phylogenetically conserved proteins like manganese dependent superoxide dismutase, thioredoxin or cyclopilin. Their IgE-binding capability can be explained by molecular mimicry resulting from shared B-cell epitopes. A common factor of IgE-binding self-antigens without sequence homology to known environmental allergens is that they elicit IgE responses only in individuals suffering from long-lasting atopic diseases. In contrast, IgE-mediated reactions to modified self-antigens might be explained with the generation of novel B-cell epitopes. Chemically modified self-antigens are likely to be recognized as non self by the immune system. The clinical relevance of IgE responses to self antigens remains largely unclear. Well documented is their ability to induce immediate Type I skin reactions in vivo, and to induce mediator release from effector cells of sensitized individuals in vitro. Based on these observations it is reasonable to assume that IgE-mediated cross-linking of FcRIepsilon receptors on effector cells can elicit the same symptoms as those induced by environmental allergens, and this could explain exacerbations of chronic allergic diseases in the absence of external exposure. However, because most of the described IgE binding self-antigens are intracellular proteins normally not accessible for antigen-antibody interactions, local release of the antigens is required to explain the induction of symptoms. PMID- 22092497 TI - An integrated methodology for process improvement and delivery system visualization at a multidisciplinary cancer center. AB - Multidisciplinary cancer centers require an integrated, collaborative, and stream lined workflow in order to provide high quality of patient care. Due to the complex nature of cancer care and continuing changes to treatment techniques and technologies, it is a constant struggle for centers to obtain a systemic and holistic view of treatment workflow for improving the delivery systems. Project management techniques, Responsibility matrix and a swim-lane activity diagram representing sequence of activities can be combined for data collection, presentation, and evaluation of the patient care. This paper presents this integrated methodology using multidisciplinary meetings and walking the route approach for data collection, integrated responsibility matrix and swim-lane activity diagram with activity time for data representation and 5-why and gap analysis approach for data analysis. This enables collection of right detail of information in a shorter time frame by identifying process flaws and deficiencies while being independent of the nature of the patient's disease or treatment techniques. A case study of a multidisciplinary regional cancer centre is used to illustrate effectiveness of the proposed methodology and demonstrates that the methodology is simple to understand, allowing for minimal training of staff and rapid implementation. PMID- 22092498 TI - The ureteroscope as a safety wire for ureteronephroscopy. AB - BACKGROUND AND PURPOSE: The recent technologic advances in the newer generation of flexible ureteroscopes have significantly enhanced the therapeutic and diagnostic efficacy of ureteroscopy. The purpose of our study was to assess ureteroscopy and lithotripsy of renal calculi without a safety wire, using the ureteroscope as the safety device. PATIENTS AND METHODS: Medical records for patients undergoing ureteroscopy by a single surgeon were retrospectively reviewed from December 2006 to December 2009. Inclusion criteria for our study included all adult patients who underwent wireless flexible ureteroscopy for the management of renal calculi and had 1 month follow-up data. RESULTS: Of the 568 patients who underwent ureteroscopy during this period, 268 patients met our study inclusion criteria. The mean age of the patients undergoing wireless ureteroscopy was 33 years, and the mean body mass index was 33.1 kg/m(2). Mean stone diameter of the renal calculi treated was 12.0+/-5.9 mm. Fifteen percent of the patients had a ureteral stent in place before the procedure, and 84% of the patients had a stent placed after ureteroscopy. Twenty percent of the patients needed ureteral dilation, and 15% of the patients had a ureteral access sheath placed intraoperatively. The overall complication rate was 2.6% (major=0.7%, minor=1.9%). Complications included: Four urinary tract infections, two patients with urosepsis, and one patient with urinary retention. No patients had ureteral perforation or ureteral avulsion. CONCLUSIONS: Using the ureteroscope as the safety mechanism, ureteroscopy is safe with regard to maintaining renal access and control. Routine safety wires during ureteronephroscopy are not necessary assuring the ureteroscope is in the kidney. PMID- 22092499 TI - Stress resiliency, psychological empowerment and conflict management styles among baccalaureate nursing students. AB - AIMS: This article is a report of a Neuman Systems Model-guided correlational study of the relations of stress resiliency, psychological empowerment, selected demographic characteristics (age, ethnicity, semester in school) and conflict management styles. BACKGROUND: Emerging evidence suggests that stress resiliency and psychological empowerment can strengthen student nurses in academic achievement and coping with stress. Little is known about conflict management styles of students and the relationship to empowerment, resiliency and the implications for managing workplace conflict. METHODS: A correlational study was conducted in Spring 2010 with 166 baccalaureate students. Most participants were female, single, Hispanic and 25 years old. The data collection instruments included the Stress Resiliency Profile, the Psychological Empowerment Instrument, the Conflict Mode Instrument and a demographic inventory. Descriptive and inferential correlational statistics were used to analyse the data. RESULTS: Students scored in the high range for focusing on their deficiencies in conflict situations; they scored above the 60th percentile for avoiding and accommodating behaviours and were less likely to use competing or collaborating strategies to manage conflict. Empowerment scores were significantly correlated with stress resiliency scores. Students with high scores on empowerment had high scores on the skill recognition subscale of the Stress Resiliency Profile suggesting more resilience; high scores on empowerment were related to high necessitating subscale scores of the Stress Resiliency Profile suggesting a predisposition to stress. CONCLUSIONS: Neuman Systems Model may provide guidance for educators to strengthen student nurses' management of stressors in the workplace. PMID- 22092500 TI - Three-phase general border detection method for dermoscopy images using non uniform illumination correction. AB - BACKGROUND: Computer-aided diagnosis of dermoscopy images has shown great promise in developing a quantitative, objective way of classifying skin lesions. An important step in the classification process is lesion segmentation. Many studies have been successful in segmenting melanocytic skin lesions (MSLs), but few have focused on non-melanocytic skin lesions (NoMSLs), as the wide variety of lesions makes accurate segmentation difficult. METHODS: We developed an automatic segmentation program for detecting borders of skin lesions in dermoscopy images. The method consists of a pre-processing phase, general lesion segmentation phase, including illumination correction, and bright region segmentation phase. RESULTS: We tested our method on a set of 107 NoMSLs and a set of 319 MSLs. Our method achieved precision/recall scores of 84.5% and 88.5% for NoMSLs, and 93.9% and 93.8% for MSLs, in comparison with manual extractions from four or five dermatologists. CONCLUSION: The accuracy of our method was competitive or better than five recently published methods. Our new method is the first method for detecting borders of both non-melanocytic and melanocytic skin lesions. PMID- 22092501 TI - Association of XRCC1, XRCC3, and NAT2 polymorphisms with the risk of oral submucous fibrosis among eastern Indian population. AB - BACKGROUND: Arecanut and smokeless tobacco usage is a major cause for oral submucous fibrosis (OSF) and its subsequent development to oral squamous cell carcinoma in South-east Asian population. Polymorphisms at N-acetyltransferase 2 locus, coding for an enzyme catalyzing acetylation of aromatic amines, might cause DNA adduct formation because of improper acetylation of these polyaromatic hydrocarbons. DNA repair enzymes remove these adduct to prevent malignancy. METHODS: In this hospital-based study, 100 controls and 88 OSF patients were genotyped at four polymorphic sites on NAT2 481 (C > T; silent), 590 (G > A; Arg197 > Gln), 803 (A > G; Lys268 > Arg), 857 (G > A; Gly286 > Glu) and two on XRCC1 18067 (C > T Arg 194 > Trp), 28152 (G > A Arg 399 > Gln), and one of XRCC3 26304 (C > T Thr 241 > Met) loci by PCR-RFLP to determine the risk of the disease. RESULTS: Heterozygous XRCC3 codon 241 [OR 2.07 (1.05-4.06)], homozygous variant of NAT C481T [OR 2.81 (1.09-7.21)], and both heterozygous and homozygous variants of NAT codon 268 and 286 [OR 2.31 (1.20-4.45) and 4.98 (1.87-13.14), and 6.12 (2.75-13.62) and 2.65 (1.04-6.72)] individually influenced susceptibility to OSF in the population. CONCLUSION: Gene-gene interaction analysis by multifactor dimensionality reduction (MDR) revealed that XRCC3 Thr 241 Met had the largest univariate effect followed by XRCC3 Thr 241 Met - NAT2 A857G in men that presents a highly synergistic interaction as one of the potential combinations of single nucleotide polymorphisms (SNPs) to increase the risk of OSF in men if exposed to arecanut or smokeless tobacco usage. These observations can speculate the impact of the studied SNPs on the etiology of OSF. PMID- 22092502 TI - Ten-year longitudinal study of gingival recession in dentists. AB - AIM: To assess the prevalence and progression/regression of gingival recession in a population sample with a high standard of oral hygiene and broad knowledge of the role of traumatic tooth brushing in the aetiology of gingival recession. MATERIAL & METHODS: Forty dental students in their final year at Dental School were examined for gingival recession in 1994 and 10 years later by the same examiner. Tooth brushing habits were ascertained in a questionnaire. Clinical parameters recorded for each recession were: recession height, probing depth, width of keratinized gingiva and bleeding on probing. Full-mouth plaque index was recorded using the modified Quigley & Hein index. RESULTS: The prevalence of gingival recession was 85% and did not change after 10 years. A total of 210 recessions found at the initial examination and 299 at the second were valid for longitudinal evaluation. Statistical differences between recessions at both examinations were found in several clinical parameters. Subjects had a significant increase in the plaque index at the second examination despite very few changes in their oral hygiene habits (p < 0.0001). CONCLUSIONS: In dentists, after 10 years, mean number of gingival recession per person and mean recession height increased while plaque control decreased. PMID- 22092503 TI - Moral enhancement via direct emotion modulation: a reply to John Harris. AB - Some argue that humans should enhance their moral capacities by adopting institutions that facilitate morally good motives and behaviour. I have defended a parallel claim: that we could permissibly use biomedical technologies to enhance our moral capacities, for example by attenuating certain counter-moral emotions. John Harris has recently responded to my argument by raising three concerns about the direct modulation of emotions as a means to moral enhancement. He argues (1) that such means will be relatively ineffective in bringing about moral improvements, (2) that direct modulation of emotions would invariably come at an unacceptable cost to our freedom, and (3) that we might end up modulating emotions in ways that actually lead to moral decline. In this article I outline some counter-intuitive potential implications of Harris' claims. I then respond individually to his three concerns, arguing that they license only the very weak conclusion that moral enhancement via direct emotion modulation is sometimes impermissible. However I acknowledge that his third concern might, with further argument, be developed into a more troubling objection to such enhancements. PMID- 22092505 TI - Diabetes mellitus: its differentiation into insulin-sensitive and insulin insensitive types. PMID- 22092504 TI - IL-13-induced MUC5AC production and goblet cell differentiation is steroid resistant in human airway cells. AB - BACKGROUND: Glucocorticosteroids (GCS) are used to treat bronchial asthma, but are not uniformly effective, especially in severe asthma. IL-13 is a T helper type 2 cytokine implicated in the pathogenesis of asthma, and IL-13 induces mucus production and goblet cell hyperplasia in airway epithelial cells. The effect of GCS on IL-13-induced mucin production is not well characterized. OBJECTIVE: The aim of this study was to evaluate the effect of dexamethasone (Dex), a potent synthetic GCS, on IL-13-induced MUC5AC mucin expression and goblet cell proliferation in differentiated normal human bronchial epithelial cells (NHBECs). METHODS: NHBECs were cultured for 14 days at an air-liquid interface with IL-13, with or without Dex. MUC5AC protein secretion and mRNA expression was determined using ELISA and quantitative real-time PCR. IL-8 production was assayed using ELISA. Histochemical analysis was performed using H&E and periodic acid-Schiff stain, and MUC5AC immunostaining. RESULTS: Although Dex dose dependently inhibited IL-8 release induced by 5 ng/mL IL-13, Dex 0.001-1 MUg/mL had no effect on IL-13 induced MUC5AC protein secretion or mRNA expression. Dex paradoxically increased MUC5AC induced by IL-13 at 0.5 and 1 ng/mL, but had no effect alone or with IL-13 at 0.1 ng/mL. Dex 0.001-1 MUg/mL did not inhibit the differentiation of cells into goblet cells and MUC5AC-positive cells induced by IL-13. CONCLUSION AND CLINICAL RELEVANCE: Dex at therapeutic concentrations did not inhibit the effects of IL-13 on goblet cell differentiation, characteristic of severe asthma. Paradoxically, MUC5AC production was increased with lower dose IL-13 exposure. This may lead to airway mucus obstruction commonly seen in life-threatening asthma. PMID- 22092507 TI - Evidence for the possible involvement of Selenomonas ruminantium in rumen fiber digestion. AB - Selenomonas ruminantium strains were isolated from sheep rumen, and their significance for fiber digestion was evaluated. Based on the phylogenetic classification, two clades of S. ruminantium (clades I and II) were proposed. Clade II is newly found, as it comprised only new isolates that were phylogenetically distant from the type strain, while all of the known isolates were grouped in the major clade I. More than half of clade I isolates displayed CMCase activity with no relation to the degree of bacterial adherence to fibers. Although none of the isolates digested fiber in monoculture, they stimulated fiber digestion when co-cultured with Fibrobacter succinogenes, and there was an enhancement of propionate production. The extent of such synergy depended on the clade, with higher digestion observed by co-culture of clade I isolates with F. succinogenes than by co-culture with clade II isolates. Quantitative PCR analysis showed that bacterial abundance in the rumen was higher for clade I than for clade II. These results suggest that S. ruminantium, in particular the major clade I, is involved in rumen fiber digestion by cooperating with F. succinogenes. PMID- 22092508 TI - Residual periodontal pockets are a risk indicator for peri-implantitis in patients treated for periodontitis. AB - OBJECTIVES: The aim of this retrospective study was to compare the clinical outcomes of implant treatment in periodontally compromised and periodontally healthy patients (PHP), with a minimum follow-up period of 5 years. METHODS: Thirty treated periodontally compromised patients (PCP) and 30 PHP, with a total of 117 Straumann implants (PCP = 56, PHP = 61) were matched for age, gender, smoking and implant characteristics. The PCP group was further stratified with patients having at least one periodontal pocket >=6 mm at follow-up examination allocated to a "residual periodontitis" (RP) group, while the remaining patients were assigned to a "no residual periodontitis" (NRP) group. These groups were compared with respect to probing pocket depth (PPD), bleeding on probing (BOP) and marginal bone loss. RESULTS: The mean follow-up period in the PCP and PHP groups was 7.99 years (range 5.04-14.40) and 8.20 years (range 5.00-13.46) respectively. There was no difference in mean PPD between the PCP and PHP groups, but the prevalence of implants with PPD >=5 mm + BOP was greater in the PCP group than in the PHP group, at both implant- (27% vs. 13%) and patient- (37% vs. 17%) level analyses. Mean implant PPD was significantly greater in the RP group (3.18 mm) than in both the NRP (2.67 mm) and PHP (2.81 mm) groups. Mean bone loss was also significantly greater in the RP group (0.68 mm) than in the NRP (0.23 mm) and PHP groups (0.26 mm). The prevalence of bone loss and PPD >=5 mm + BOP at the implant level was significantly greater for the RP group compared with both the NRP and PHP groups. CONCLUSIONS: Implants in PCP with residual pocketing at follow-up had increased PPD and bone loss compared with implants placed in PHP and PCP without residual pocketing. Hence, it is the maintenance of periodontal health rather than a previous history of periodontitis that is the critical determinant of increased risk of peri-implantitis, highlighting the importance of effective periodontal therapy and maintenance in patients with a history of periodontitis. PMID- 22092509 TI - Impaired force control during food holding and biting in subjects with tooth- or implant-supported fixed prostheses. AB - AIM: Our goal here was to assess the ability of subjects with their natural teeth (natural), bimaxillary tooth-supported bridges (bridge) and bimaxillary implant supported bridges (implant) to control the low contact and high biting forces associated with holding and splitting food between the teeth. MATERIALS AND METHODS: Ten subjects in each of these groups performed a task involving holding and splitting morsels of food with different degrees of hardness (biscuits and peanuts) between a pair of opposing central incisors. RESULTS: The hold force employed by the implant group was significantly higher and more variable than the corresponding force exerted by the bridge group, whereas the natural group used lowest and least variable force. For all three groups, the split force was higher and the split phase duration longer with peanuts than for biscuits. In the case of the natural group, a significantly higher rate of force increase (peak force rate) was observed when splitting peanuts when compared with biscuits, whereas no such difference could be seen for the other two groups. CONCLUSION: These findings demonstrate that individuals with bimaxillary tooth- or implant supported bridges (in whom sensory information provided by the periodontal mechanoreceptors is impaired or missing) are unable to apply low-hold forces at the levels of individuals with natural teeth or to adapt the rate of the split force to the hardness of the food. We thus conclude that adequate sensory information from periodontal mechanoreceptors is essential for normal control of both low contact and high biting forces. PMID- 22092510 TI - Foot pressure and center of pressure in athletes with ankle instability during lateral shuffling and running gait. AB - This study evaluates foot pressure and center of pressure (COP) patterns in individuals with ankle instability during running and lateral shuffling. Eleven participants with ankle instability (AI) and 11 normal subjects (Normal) performed running and lateral shuffling tasks. The outcome measures were foot progression angle, peak pressure, and displacement of COP during stance phase. During running, the foot progression angle, that is, the angle of foot abduction, was lower in the AI group (Normal: 13.46 degrees +/- 4.45 degrees ; AI: 8.78 degrees +/- 3.91 degrees ), and the 1st metatarsal contact pressure (Normal: 0.76 +/- 0.47 N/cm(2).kg; AI: 1.05 +/- 0.70 N/cm(2).kg) and the 3rd metatarsal peak pressure were higher in the AI (Normal: 0.96 +/- 0.60 N/cm(2).kg; AI: 1.54 +/- 0.68 N/cm(2).kg). The medial-lateral (M-L) COP in the late-stance phase of running for the AI group transferred faster from lateral to medial foot than the Normal group. For lateral shuffling, the AI group had greater peak pressure at the 1st (Normal: 0.76 +/- 0.67 N/cm(2).kg; AI: 1.49 +/- 1.04 N/cm(2).kg), 2nd (Normal: 0.57 +/- 0.39 N/cm(2).kg; AI: 0.87 +/- 0.68 N/cm(2).kg), 3rd (Normal: 0.70 +/- 0.54 N/cm(2).kg; AI: 1.42 +/- 0.87 N/cm(2).kg), and 4th (Normal: 0.52 +/ 0.38 N/cm(2).kg; AI: 1.12 +/- 0.78 N/cm(2).kg) metatarsal areas than the Normal group. The M-L COP located more laterally from the early to mid-stance phase in the AI compared with the Normal group. The findings suggest that COP displacement during lateral shuffle may be a factor in ankle instability while the foot progression angle during running may be a compensatory strategy. PMID- 22092511 TI - Diffuse cutaneous mastocytosis: analysis of 10 cases and a brief review of the literature. AB - BACKGROUND: Diffuse cutaneous mastocytosis (DCM) is an extremely rare disease characterized by mast cell (MCs) infiltration of the entire skin. Little is known about the natural course of DCM. OBJECTIVES: We decided to characterize clinical manifestations, the frequency of MCs mediator-related symptoms and anaphylaxis, risk of systemic mastocytosis (SM) and prognosis, based on 10 cases of DCM, the largest series published to date. METHODS: Diffuse cutaneous mastocytosis, DCM was confirmed by histopathological examination of skin samples in all cases. SCORing Mastocytosis (SCORMA) Index was used to assess the intensity of DCM. The analysis of clinical symptoms and laboratory tests, including serum tryptase levels was performed. Bone marrow biopsy was done only in selected cases. RESULTS: Large haemorrhagic bullous variant of DCM (five cases) and infiltrative small vesicular variant (five cases) were identified. The skin symptoms appeared in age-dependent manner; blistering predominated in infancy, whereas grain leather appearance of the skin and pseudoxanthomatous presentation developed with time. SM was not recognized in any of the patients. Mast cell mediator-related symptoms were present in all cases. Anaphylactic shock occurred in three patients. Follow-up performed in seven cases revealed slight improvement of skin symptoms, reflected by decrease of SCORMA Index in all of them. Serum tryptase levels declined with time in six cases. CONCLUSIONS: Diffuse cutaneous mastocytosis, DCM is a heterogeneous, severe, cutaneous disease, associated with mediator-related symptoms and risk of anaphylactic shock. Although our results suggest generally favourable prognosis, the review of the literature indicate that SM may occur. Therefore, more guarded prognosis should be given in DCM patients. PMID- 22092512 TI - Is oral health-related quality of life stable following rehabilitation with mandibular two-implant overdentures? AB - OBJECTIVES: The superiority of mandibular two-implant overdentures (IODs) over conventional complete dentures (CDs) in terms of quality of life is still questioned. Furthermore, the stability and magnitude of the treatment effect over time remain uncertain. This follow-up study aimed to determine the stability and magnitude of the effect of IODs on oral health-related quality of life (OHRQoL). MATERIAL AND METHODS: 172 participants (mean age 71 +/- 4.5 years) randomly received CDs or IODs, both opposed by conventional maxillary dentures. OHRQoL was measured using the Oral Health Impact Profile (OHIP-20) at baseline, 1 and 2 years post-treatment. Repeated measures ANOVAs were conducted to assess the effects of time and treatment on the total OHIP and its individual domain scores. RESULTS: A statistically significant improvement in OHRQoL was seen for both treatment groups (P < 0.001). This improvement was maintained over the 2 year assessment. At both follow-ups, participants wearing IODs reported significantly better total OHIP scores than those wearing CDs (P < 0.001), with a 1.5 times larger magnitude of effect. In the CD group, baseline OHIP scores influenced the post-treatment scores (P < 0.001). This effect was not found in the IOD group. CONCLUSIONS: The effect of mandibular two-IODs on OHRQoL is stable over a 2-year period. The large magnitude of effect of this treatment supports its clinical significance. PMID- 22092513 TI - Is vibration exercise a useful addition to a weight management program? AB - Vibration exercise (VbX) has received a lot of attention as an exercise modality, which evokes muscular work and elevates metabolic rate that could be a potential method for weight reduction. Popular press has purported that VbX is quick and convenient, and 10 min of VbX is equivalent to 1 h of traditional exercise, where it has been marketed as the new weight-loss and body toning workout. However, research studies have shown that muscle activation occurs but the energy demand in response to VbX is quite low, where exhaustive VbX reported a metabolic demand of 23 mL/kg/min compared with 44 mL/kg/min from an exhaustive cycle test. Different vibration frequencies with varying amplitudes and loads have been tested, but only small increases in metabolic rate have been reported. Based on these findings, it has been indirectly calculated that a VbX session of 26 Hz for three continuous minutes would only incur a loss of ~ 10.7 g fat/h. Following a 24-week program of VbX, no observed differences were found in body composition, and following 12 months of VbX, the time to reach peak V O2 was significantly higher in conventional exercise compared with VbX. However, one study has reported that percentage body fat decreased by 3.2% after 8 months after VbX in comparison with resistance and control groups that performed no aerobic conditioning. The evidence to date suggests that VbX can increase whole and local oxygen uptake; however, with additional load, high vibration frequency, and/or amplitude, it cannot match the demands of conventional aerobic exercise. Therefore, caution is required when VbX programs are solely used for the purpose of reducing body fat without considering dietary and aerobic conditioning guidelines. PMID- 22092514 TI - Comparison of platelet rich fibrin and collagen as osteoblast-seeded scaffolds for bone tissue engineering applications. AB - OBJECTIVES: The loss of jaw bone caused by different kinds of pathologies leads to dysfunction and reduced quality of life in affected patients. Thus, the pivotal goal in bone tissue engineering is to reconstruct these defects. The essential precondition for new tissue generation is an extracellular matrix which acts as a scaffold so that cells can migrate, differentiate, and proliferate. Fibrin, a biopolymer responsible for blood clot formation, has been shown to be suitable for tissue engineering applications. The aim of the present study is a comparison of platelet rich fibrin (PRF) with the commonly used collagen membrane BioGide((r)) as a scaffold for human osteoblast cell seeding for bone tissue engineering. MATERIAL AND METHODS: Human osteoblasts were cultured with eluates from PRF (n = 7) and BioGide((r)) (n = 8) membranes incubated in serum-free cell culture medium. Vitality of these cells was assessed by fluorescein diacetate and propidium iodide staining, biocompatibility with the lactate dehydrogenase test and proliferation levels with the MTT ([3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium-bromide]), and BrdU (5-bromo-2-deoxyuridine) tests. In addition, human osteoblasts were seeded on both membrane systems and cell growth was compared by the water soluble tetrazolium (WST-1) (4-[3-(4-iodophenyl)-2-(4 nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) test and scanning electron microscopy (SEM). Osteoblastic differentiation was assessed by alkaline phosphatase activity measured by ELISA in the supernatant of osteoblasts cultivated on PRF membranes (n = 10), PRF clots (n = 10), and BioGide((r)) membranes (n = 10). RESULTS: Lactate dehydrogenase test values were higher for PRF compared to BioGide((r)) . The BrdU test showed superior cell growth after cultivation in eluate from PRF than in eluate from BioGide((r)) . The WST-1 assay demonstrated superior cell proliferation on PRF than on BioGide((r)) . SEM revealed osteoblast colonization of both membranes. Cultivation of osteoblasts on PRF membranes and PRF clots showed significantly higher alkaline phosphatase activity than on BioGide((r)) membranes. CONCLUSION: Metabolic activity and proliferation of human osteoblast cells in vitro were supported to a significant higher extent by eluates from PRF membranes. Both membranes are suitable as scaffolds for cultivation of human osteoblast cells in vitro; proliferation was significant higher on PRF membranes and on PRF clot than on BioGide((r)) membranes. PMID- 22092515 TI - Automated 15-minute cytokeratin 7 immunostaining protocol for extramammary Paget's disease in Mohs micrographic surgery. PMID- 22092517 TI - High diversity in populations of the introduced plant pathogen, Cryphonectria parasitica, due to encounters between genetically divergent genotypes. AB - The ascomycete fungus Cryphonectria parasitica is an aggressive introduced pathogen of sweet chestnut (Castanea sativa Mill.). It has spread throughout the chestnut-growing areas of Europe, with higher diversity in the regions close to its first introduction and lower diversity in its expanding ranges in Europe. To reconstruct the invasion events that could explain the high diversity of C. parasitica in Croatia and Slovenia, 180 samples were genotyped using 11 sequence characterized amplified region markers. Eight of 11 loci were found to be polymorphic, and a total of 66 different haplotypes were identified. Bayesian clustering indicated the existence of two clusters, which suggests two separate introductions of C. parasitica in these regions. The first cluster is dominant in western parts of Croatia and Slovenia and the second in eastern and northern regions. The data analysis indicates that northern Italy was the first source of infection, with the subsequent introduction from south-eastern Europe, which contributed significantly to the diversity of the C. parasitica populations tested. Most haplotypes were probably derived through sexual recombination between a few divergent haplotypes, which suggests that multiple introductions and sexual reproduction are important for the formation of genetically diverse C. parasitica populations. PMID- 22092516 TI - A specific mix of generalists: bacterial symbionts in Mediterranean Ircinia spp. AB - Microbial symbionts form abundant and diverse components of marine sponge holobionts, yet the ecological and evolutionary factors that dictate their community structure are unresolved. Here, we characterized the bacterial symbiont communities of three sympatric host species in the genus Ircinia from the NW Mediterranean Sea, using electron microscopy and replicated 16S rRNA gene sequence clone libraries. All Ircinia host species harbored abundant and phylogenetically diverse symbiont consortia, comprised primarily of sequences related to other sponge-derived microorganisms. Community-level analyses of bacterial symbionts revealed host species-specific genetic differentiation and structuring of Ircinia-associated microbiota. Phylogenetic analyses of host sponges showed a close evolutionary relationship between Ircinia fasciculata and Ircinia variabilis, the two host species exhibiting more similar symbiont communities. In addition, several bacterial operational taxonomic units were shared between I. variabilis and Ircinia oros, the two host species inhabiting semi-sciophilous communities in more cryptic benthic habitats, and absent in I. fasciculata, which occurs in exposed, high-irradiance habitats. The generalist nature of individual symbionts and host-specific structure of entire communities suggest that: (1) a 'specific mix of generalists' framework applies to bacterial symbionts in Ircinia hosts and (2) factors specific to each host species contribute to the distinct symbiont mix observed in Ircinia hosts. PMID- 22092518 TI - Damping behavior of implant-supported restorations. AB - OBJECTIVES: The aim of the present study was to assess the shock absorbing capacity of implant-supported restorations (CAD/CAM composite resin or zirconia abutment with composite resin or porcelain crown/onlay) and a simulated natural tooth complex using the Periometer((r)) . MATERIAL AND METHODS: One hundred and twenty Morse taper implants (Titamax CM 11 mm) were mounted on bone-simulating acrylic resin base and restored with CAD/CAM zirconia (60) and metal composite resin Paradigm MZ100 (60) abutments. Using CEREC3, standardized onlays (60) and crowns (60) were designed and milled in ceramic (Paradigm C) or composite resin (Paradigm MZ100) to simulate a maxillary premolar. All restorations were luted with a preheated light curing composite resin (Filtek Z100). Fifteen extracted human upper premolars were mounted with a simulated PDL and used as control group. The Periometer((r)) , a new handheld percussion probe that measures the energy loss coefficient (LC) for both natural teeth and implant-supported structures, was positioned perpendicularly to the buccal surface of each restoration. Three measurements of the LC were collected for each specimen. The effect of each variable (abutment material, restoration material, and restoration design) on the LC was explored using multiple regression analysis. RESULTS: Differences in LC between the abutment material (zirconia/Paradigm MZ100), the restoration material (Paradigm C/Paradigm MZ100) and the restoration design (onlay/crown) were recorded. The average LC of zirconia and metal composite resin abutments ranged from 0.040 to 0.053 and 0.059 to 0.068, respectively. Zirconia abutments restored with composite resin restorations (LC 0.051-0.053) had the closest LC value when compared with teeth with simulated PDL (0.049). CONCLUSION: Composite resin onlays/crowns bonded to zirconia implant abutments presented similar dynamic response to load (damping behavior) when compared to teeth with a simulated PDL. PMID- 22092520 TI - Current literature. PMID- 22092519 TI - Low-carbohydrate diets for weight loss: the pros and cons. PMID- 22092521 TI - Plastinated heart slices aid echocardiographic interpretation in the dog. AB - Our aim was to compare plastinated sections of the canine heart with corresponding two-dimensional (2D) echocardiographic images. Thirteen dog hearts were fixed by dilation and then processed by the S10 silicon plastination method (Biodur). Two dogs without evidence of cardiac disease were imaged using 2D echocardiography so as to obtain a complete series of the standard right and left parasternal images, which were compared with corresponding plastinated slices obtained by knife sectioning of the hearts. The plastinated slices revealed the internal anatomy of the heart with great detail and were particularly useful to display the spatial relationship between complex anatomic structures. The plastinated slices corresponded accurately with the echocardiographic images. Because of the dilation of the right heart during the fixation process, it was not possible to obtain plastinated specimens in ventricular systole. This paper may be a reference atlas for assisting 2D echocardiography interpretation. PMID- 22092522 TI - Application of phylogenetic microarrays to interrogation of human microbiota. AB - Human-associated microbiota is recognized to play vital roles in maintaining host health, and it is implicated in many disease states. While the initial surge in the profiling of these microbial communities was achieved with Sanger and next generation sequencing, many oligonucleotide microarrays have also been developed recently for this purpose. Containing probes complementary to small ribosomal subunit RNA gene sequences of community members, such phylogenetic arrays provide direct quantitative comparisons of microbiota composition among samples and between sample groups. Some of the developed microarrays including PhyloChip, Microbiota Array, and HITChip can simultaneously measure the presence and abundance of hundreds and thousands of phylotypes in a single sample. This review describes the currently available phylogenetic microarrays that can be used to analyze human microbiota, delineates the approaches for the optimization of microarray use, and provides examples of recent findings based on microarray interrogation of human-associated microbial communities. PMID- 22092524 TI - Hypersensitivity reaction to chromated glycerin. PMID- 22092523 TI - Shackling incarcerated pregnant women. PMID- 22092525 TI - Effects of the Bam earthquake on employment: a shift-share analysis. AB - Disasters have potential short-term and long-term impacts on employment and employment structures in affected regions. While measuring the full economic impact of a disaster requires sophisticated econometrics and mathematical simulations, conventional regional economic models such as shift-share analysis can be used to assess some of these effects. This paper applies shift-share analysis to understand potential long-term impacts of disasters on employment using the December 2003 Bam earthquake as a case study. The results provide further evidence that disasters could have significant long-term effects on the employment structure of affected regions. PMID- 22092526 TI - Gingival changes during pregnancy: III. Impact of clinical, microbiological, immunological and socio-demographic factors on gingival inflammation. AB - AIMS: To identify predictor variables involved in exacerbated gingival inflammation associated with pregnancy. MATERIAL AND METHODS: In this cohort study, 48 pregnant and 28 non-pregnant women without periodontitis were included. The pregnant women were evaluated in the first, second and third trimester and at 3 months postpartum, whilst the non-pregnant women were evaluated twice, with a 6 month interval. At each visit, clinical [plaque index (PlI) and gingival index (GI)], hormonal (salivary progesterone and estradiol), immunological [gingival crevicular fluid interleukin-1beta, interleukin-6, tumour necrosis factor-alpha (TNF-alpha) and prostaglandin-E(2) ] and microbiological (periodontal pathogens culture) evaluations were performed. Statistical analysis was undertaken using exhaustive chi-square automatic interaction detection (exhaustive CHAID) to analyse the predictive value of the independent outcomes to develop pregnancy GI. RESULTS: PlI was the strongest predictor implicated in the GI throughout pregnancy and after delivery. During the second and third trimesters the presence of Porphyromonas gingivalis significantly contributed to the worsening of gingival inflammation. When compared with the non-pregnant group, significant differences were found in TNF-alpha amounts and concentrations and in the third trimester site-specific GI. CONCLUSIONS: Bacterial challenge to the gingival tissues, both quantitatively (PlI) and qualitatively (harbouring P. gingivalis) appears to affect the level of gingival inflammation observed during pregnancy. PMID- 22092527 TI - Survey of the efficacy of a short fragment of the rbcL gene as a supplemental DNA barcode for diatoms. AB - DNA barcoding is a tool that uses a short, standard segment of DNA to identify organisms. In diatoms, a consensus on an appropriate DNA barcode has not been reached, but several markers show promise. These include the 5.8S gene plus a fragment of the internal transcribed spacer 2 (ITS-2) of nuclear-encoded ribosomal RNA, a 420-bp segment of the 18S rRNA gene, and a 748-bp fragment at the 3'-end of the ribulose bisophosphate carboxylase large subunit (rbcL) gene. Here, we tested a 540-bp fragment 417-bp downstream of the start codon of the rbcL gene for its efficacy in distinguishing diatom species in a wide range of taxa. Overall, 381 sequences representing 66 genera and 245 species from the classes Mediophyceae and Bacillariophyceae were examined. Intra/interspecific thresholds were set at p = 0.01 differences per site (diff./site) for Mediophyceae and p = 0.02 diff./site for Bacillariophyceae and correctly segregated 96% and 93% of morphological congeners, respectively. When testing reproductively isolated or biological species, which are only available from Bacillariophyceae, 80% of species were discriminated. Therefore, we concluded that, alone, the rbcL region tested herein as potential a DNA barcode was not a sufficient discriminator of all diatoms. We suggest that this fragment could be used in a dual-locus barcode with the more variable 5.8S+ITS-2 to discriminate species without sufficient interspecific divergences in the tested rbcL region and to provide insight into species identity from a separately evolved genome. PMID- 22092528 TI - Acanthamoeba belonging to T3, T4, and T11: genotypes isolated from air conditioning units in Santiago, Chile. AB - Free-living amoebae (FLA) of the genus Acanthamoeba are widely distributed in the environment, in the air, soil, and water, and have also been isolated from air conditioning units. The objective of this work was to investigate the presence of this genus of FLA in the air-conditioning equipment at the Institute of Public Health of Chile in Santiago, Chile. Water and air samples were collected from air conditioning systems and were checked for the presence of Acanthamoeba spp. Positive samples were further classified at the genotype level after sequencing the highly variable diagnostic fragment 3 (DF3) region of the 18S rRNA gene. This is the first report of the T3, T4, and T11 genotypes of Acanthamoeba in air conditioning units from Chile. Overall, the widespread distribution of potentially pathogenic Acanthamoeba strains in the studied source demands more awareness within the public and health professionals in Chile as this pathogen is emerging as a risk for human health worldwide. PMID- 22092530 TI - Association of vitamin D and antimicrobial peptide production during late-phase allergic responses in the lung. AB - BACKGROUND: Vitamin D may play important roles in regulating immune responses and in defence against infectious diseases by effects on both innate and adaptive immune responses. Little is known regarding activation of vitamin D within airway tissues and its relationship to inflammation and antimicrobial responses. OBJECTIVE: The objective of this study was to investigate the activation of vitamin D within the airways and to define relationships between vitamin D metabolites and measures of inflammatory and antimicrobial responses assessed by bronchoalveolar lavage (BAL) during late-phase responses following allergen challenge of allergic subjects. METHODS: Segmental allergen challenge was performed with saline and allergen in 16 adult allergic subjects. BAL was performed in both saline and allergen-challenged sites 20-24 h. after challenge. Following extraction from BAL fluids, levels of 25-hydroxy-vitamin D (25(OH)D) and 1,25-dihydroxy-vitamin D (1,25(OH)(2)D) were assayed by specific radioimmunoassays. The cleavage product of cathelicidin, LL-37, was assayed by ELISA. Cellular constituents and albumin were measured. RESULTS: Levels of vitamin D metabolites were increased in concentrated BAL fluids after allergen compared to saline challenge. Levels of 1,25(OH)(2)D increased from largely undetectable to 2.5 pm (median; range: 1-29.5; P = 0.005) while 25(OH)D increased from 3.2 (0.8-6.2) to 6.2 (1.5-184.9) nm (P = 0.0006). Levels of LL-37 increased from 2.1 (1.4-4.1) to 14.5 (2.2-106.7) ng/mL BAL (P = 0.0005). Levels of LL-37, 1,25(OH)(2)D, and 25(OH)D following allergen challenge were correlated with each other (P < 0.0001), cellular changes, and levels of albumin (P < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Levels of vitamin D metabolites, particularly 1,25(OH)(2)D, were low within the airways and increased after allergen challenge. The increases correlated with the magnitude of inflammation and increases in cathelicidin. Normalization to albumin suggested plasma exudation as a mechanism for the increases. The findings support a role for vitamin D in allergic and innate immune responses in the lung. PMID- 22092532 TI - Analysis of human perception of facial skin radiance by means of image histogram parameters of surface and subsurface reflections from the skin. AB - BACKGROUND: The appearance of the skin is the result of complicated light-skin interactions involving surface and subsurface reflections. Radiant skin is a complicated attribute but is important for skin beauty. The aim of the present study was to achieve an understanding of the association between human perceptions of skin radiance and image histogram parameters from technically recorded images of surface and subsurface reflections. METHODS: Facial images of 45 subjects were evaluated visually by 30 respondents and were also computer analyzed in terms of their image histogram parameters. A partial least squares regression model was created to explain visual perceptions in terms of the image histogram parameters. RESULTS: Visual perceptions of subsurface reflections can be explained in terms of the mean from the subsurface reflection image histogram, and visual perceptions of surface reflections can be explained in terms of the standard deviation (SD) and skewness from the surface reflection image histogram. Skin radiance can be explained in terms of the mean from the subsurface reflection and the SD from the surface reflection. CONCLUSION: To acquire skin radiance, a surface reflection component that makes the skin look shiny and a subsurface reflection component that is in line with skin fairness are both needed. A balance of these features provides the origin of skin radiance. PMID- 22092531 TI - CDKB2 is involved in mitosis and DNA damage response in rice. AB - DNA damage checkpoints delay mitotic cell-cycle progression in response to DNA stress, stalling the cell cycle to allow time for repair. CDKB is a plant specific cyclin-dependent kinase (CDK) that is required for the G2/M transition of the cell cycle. In Arabidopsis, DNA damage leads the degradation of CDKB2, and the subsequent G2 arrest gives cells time to repair damaged DNA. G2 arrest also triggers transition from the mitotic cycle to endoreduplication, leading to the presence of polyploid cells in many tissues. In contrast, in rice (Oryza sativa), polyploid cells are found only in the endosperm. It was unclear whether endoreduplication contributes to alleviating DNA damage in rice (Oryza sativa). Here, we show that DNA damage neither down-regulates Orysa;CDKB2;1 nor induces endoreduplication in rice. Furthermore, we found increased levels of Orysa;CDKB2;1 protein upon DNA damage. These results suggest that CDKB2 functions differently in Arabidopsis and rice in response to DNA damage. Arabidopsis may adopt endoreduplication as a survival strategy under genotoxic stress conditions, but rice may enhance DNA repair capacity upon genotoxic stress. In addition, polyploid cells due to endomitosis were present in CDKB2;1 knockdown rice, suggesting an important role for Orysa;CDKB2;1 during mitosis. PMID- 22092533 TI - Salt induces biosynthesis of hemolytically active compounds in the xerotolerant food-borne fungus Wallemia sebi. AB - Wallemia sebi is a xerotolerant, ubiquitous, food-borne, mycotoxigenic fungus. An ethanol extract of its mycelium demonstrated a strong hemolytic activity, which was further enhanced at high salt concentrations in the growth medium. Characterization of the extract using gas chromatography-mass spectrometry revealed a mixture of sterols and unsaturated fatty acids, indicating the latter as responsible for the hemolytic activity. The lytic activity of the extract is here studied using red blood cells and artificial small lipid vesicles with various lipid compositions. This shows concentration-dependent hemolysis and preferential activity toward lipid membranes with greater fluidity. The W. sebi lytic activity on mammalian erythrocytes shows its potential involvement in the formation of lesions in subcutaneous infections, in farmer's lung disease, and in consumption of food and feed that are contaminated with food-borne W. sebi. PMID- 22092534 TI - Reducing errors benefits the field-based learning of a fundamental movement skill in children. AB - Proficient fundamental movement skills (FMS) are believed to form the basis of more complex movement patterns in sports. This study examined the development of the FMS of overhand throwing in children through either an error-reduced (ER) or error-strewn (ES) training program. Students (n = 216), aged 8-12 years (M = 9.16, SD = 0.96), practiced overhand throwing in either a program that reduced errors during practice (ER) or one that was ES. ER program reduced errors by incrementally raising the task difficulty, while the ES program had an incremental lowering of task difficulty. Process-oriented assessment of throwing movement form (Test of Gross Motor Development-2) and product-oriented assessment of throwing accuracy (absolute error) were performed. Changes in performance were examined among children in the upper and lower quartiles of the pretest throwing accuracy scores. ER training participants showed greater gains in movement form and accuracy, and performed throwing more effectively with a concurrent secondary cognitive task. Movement form improved among girls, while throwing accuracy improved among children with low ability. Reduced performance errors in FMS training resulted in greater learning than a program that did not restrict errors. Reduced cognitive processing costs (effective dual-task performance) associated with such approach suggest its potential benefits for children with developmental conditions. PMID- 22092535 TI - Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. AB - Interleukin-5 is a Th2 homodimeric cytokine involved in the differentiation, maturation, migration, development, survival, trafficking and effector function of blood and local tissue eosinophils, in addition to basophils and mast cells. The IL-5 receptor (IL-5R) consists of an IL-5-specific alpha subunit that interacts in conformationally dynamic ways with the receptor's betac subunit, an aggregate of domains it shares with binding sites of IL-3 and granulocyte macrophage colony-stimulating factor. IL-5 and IL-5R drive allergic and inflammatory immune responses characterizing numerous diseases, such as asthma, atopic dermatitis, chronic obstructive pulmonary disease, eosinophilic gastrointestinal diseases, hyper-eosinophilic syndrome, Churg-Strauss syndrome and eosinophilic nasal polyposis. Although corticosteroid therapy is the primary treatment for these diseases, a substantial number of patients exhibit incomplete responses and suffer side-effects. Two monoclonal antibodies have been designed to neutralize IL-5 (mepolizumab and reslizumab). Both antibodies have demonstrated the ability to reduce blood and tissue eosinophil counts. One additional monoclonal antibody, benralizumab (MEDI-563), has been developed to target IL-5R and attenuate eosinophilia through antibody-dependent cellular cytotoxicity. All three monoclonal antibodies are being clinically evaluated. Antisense oligonucleotide technology targeting the common betac IL-5R subunit is also being used therapeutically to inhibit IL-5-mediated effects (TPI ASM8). Small interfering RNA technology has also been used therapeutically to inhibit the expression of IL-5 in animal models. This review summarizes the structural interactions between IL-5 and IL-5R and the functional consequences of such interactions, and describes the pre-clinical and clinical evidence supporting IL 5R as a therapeutic target. PMID- 22092536 TI - Paracetamol and opioid pathways: a pilot randomized clinical trial. AB - Previous studies suggest that the antinociceptive action of paracetamol (acetaminophen, APAP) might involve descending inhibitory pain pathways and the opioidergic system: this study explores this issue in humans with naloxone, the opioid antagonist. After ethical approval, 12 healthy male volunteers were included in this randomized, controlled, double-blind, crossover, four-arm study. They were administered intravenous paracetamol (APAP 1 g) or saline (placebo, pl) followed at 100 min with IV naloxone (Nal 8 mg) or saline, every week for 4 weeks. The amplitude of cerebral potentials evoked by thermal/painful stimuli applied on the arm was recorded nine times over 150 min, witnessing of pain integration at central level. Amplitude changes as well as areas under the curve (AUCs) over 150 min were compared for the four treatments by repeated measures ANOVA (significance 0.05). Amplitude changes were significant for APAP/pl vs. pl/pl at t150: -44% (95%CI -58 to -30) vs. -27% (95%CI -37 to -17; P < 0.05) but not vs. APAP/Nal. AUC (0-150) of APAP/pl is significantly different from pl/pl ( 3452%.min (95%CI -4705 to -2199) vs. -933% min (95%CI -2273 to 407; P = 0.015) but not from APAP/Nal (-1731% min (95%CI -3676 to 214; P = 0.08) and other treatments. AUC (90-150) is not significantly different. This pilot study shows for the first time in human volunteers that naloxone does not inhibit paracetamol antinociception, suggesting no significant implication of the opioid system in paracetamol mechanism of action: this needs be confirmed on a larger number of subjects. PMID- 22092537 TI - Neurolytic effects of ampicillin on the rat infraorbital nerve. AB - PURPOSE: The aim of this study was to investigate the histomorphological changes of the infraorbital nerve of rats treated with ampicillin. MATERIALS AND METHODS: The infraorbital nerve was approached through the infraorbital foramen, and 0.01 ml of ampicillin dissolved in distilled water was injected taking care not to damage the nerve. Saline solution was used in control animals. Nerves were dissected and after routine histology processing analysed by light microscopy. RESULTS: Cross-section of the nerve treated with ampicillin showed damaged axons with disintegration of heavily myelinated fibres, while thinly myelinated fibres remain unaffected. In the saline group, no damage was observed. The signs of regeneration of the damaged infraorbital nerves were detected on the fourth post operative week. CONCLUSION: Ampicillin can cause peripheral nerve damage when injected perineurally. PMID- 22092538 TI - Penicillin-resistant Streptococcus pyogenes? PMID- 22092539 TI - Stem cell treatments in China: rethinking the patient role in the global bio economy. AB - The paper looks in detail at patients that were treated at one of the most discussed companies operating in the field of untried stem cell treatments, Beike Biotech of Shenzhen, China. Our data show that patients who had been treated at Beike Biotech view themselves as proactively pursuing treatment choices that are not available in their home countries. These patients typically come from a broad variety of countries: China, the United Kingdom, the United States, South Africa and Australia. Among the patients we interviewed there seemed to be both an awareness of the general risks involved in such experimental treatments and a readiness to accept those risks weighed against the possible benefits. We interpret this evidence as possibly reflecting the emergence of risk-taking patients as 'consumers' of medical options as well as the drive of patients to seek treatment options in the global arena, rather than being hindered by the ethical and regulatory constraints of their home countries. Further, we found that these patients tend to operate in more or less stable networks and groups in which they interact and cooperate closely and develop opinions and assessments of available treatment options for their ailments. These patients also perform a multiple role as patients, research subjects, and research funders because they are required to pay their way into treatment and research activities. This new social dynamics of patienthood has important implications for the ethical governance of stem cell treatments. PMID- 22092540 TI - Stability of cp-Ti and Ti-6Al-4V alloy for dental implants as a function of saliva pH - an electrochemical study. AB - OBJECTIVES: To investigate the role of different levels of pH of artificial saliva under simulated oral environment on the corrosion behavior of commercially pure titanium (cp-Ti) and Ti-6Al-4V alloy. Special attention is given to understand the changes in corrosion kinetics and surface characterization of Ti by using electrochemical impedance spectroscopy (EIS). MATERIALS AND METHODS: Fifty-four Ti disks (15-mm diameter, 2-mm thickness) were divided into six groups (n = 9) as a function of saliva pH (3, 6.5, and 9) and Ti type. Samples were mechanically polished using standard metallographic procedures. Standard electrochemical tests, such as open circuit potential, EIS, and potentiodynamic tests were conducted in a controlled environment. Data were evaluated by two-way ANOVA, Tukey multiple comparison test, and independent t-test (alpha = 0.05). Ti surfaces were examined using white-light-interferometry microscopy and scanning electron microscopy (SEM). RESULTS: Saliva pH level significantly affected the corrosion behavior of both Ti types. At low pH, acceleration of ions exchange between Ti and saliva, and reduction of resistance of Ti surface against corrosion were observed (P < 0.05). Corrosion rate was also significantly increased in acidic medium (P < 0.05). Similar corrosion behavior was observed for both Ti types. The white-light-interferometry images of Ti surfaces show higher surface changes at low pH level. SEM images do not show detectable changes. No pitting corrosion was observed for any group. CONCLUSIONS: The pH level of artificial saliva influences the corrosion behavior of cp-Ti and Ti-6Al 4V alloy in that lower pH accelerates the corrosion rate and kinetics. The corrosion products may mitigate the survival rate of dental implants. PMID- 22092541 TI - Comparison of strength development with resistance training and combined exercise training in type 2 diabetes. AB - Resistance training has been shown to increase strength in type 2 diabetes; however, it is unclear if combining resistance and aerobic training (A + R) impedes strength development compared with resistance training only (R). The purpose of this study was to compare changes in strength with A + R vs R in individuals with type 2 diabetes. We evaluated monthly workload increments in participants from the Diabetes Aerobic and Resistance Exercise clinical trial. Muscular strength was assessed through training volumes and as the eight repetition maximum (8-RM) at 0, 3, and 6 months. Both groups increased their upper and lower body volumes monthly for 6 months. The relative increase in upper body workload in R was significantly greater than A + R at 4 months (161 +/- 11% vs 127 +/- 11%, P = 0.009) and at 6 months of training (177 +/- 11% vs 132 +/- 11%, P = 0.008). Both groups had improvements in 8-RM workloads at 3 and 6 months. The resistance training group had a significantly greater improvement in 8-RM on the leg press at 6 months compared with A + R (80 +/- 11% vs 58 +/- 8%, P = 0.045). Both R and A + R improved strength with a 6-month training program; however, increases in strength may be greater with resistance training alone compared with performing both aerobic and resistance training. PMID- 22092542 TI - Application of self-regulation theory and motivational interview for improving oral hygiene: a randomized controlled trial. AB - AIM: Because patient adherence to oral hygiene is essential for periodontal treatment success, the aim of the study was to assess whether a motivational interview addressing the five dimensions of Leventhal's theory performed better than conventional basic instruction on improving compliance with plaque control among patients with periodontitis. MATERIALS AND METHODS: A randomized controlled clinical trial design was used in which a group of patients underwent a motivational interview in addition to classical consultation. A control group received only the standard consultation. The O'Leary Plaque Index was used to judge the oral hygiene at baseline and at 1 month follow-up. Patient satisfaction with the dental visit was scored using a specific questionnaire. RESULTS: At baseline, the mean full mouth plaque score varied between 55% (experimental group) and 58% (control group). Patients in the experimental group had a higher oral hygiene improvement (21 +/- 20% versus 4 +/- 5%, p < 0.001) 1 month post treatment. The motivational interview resulted in greater satisfaction scores compared with those of patients in the control group: 10.55 +/- 1.53 versus 8.82 +/- 2.40, p = 0.014. CONCLUSIONS: This new concept of motivational interview is a promising approach and can be useful for counselling-related periodontal disorders. PMID- 22092543 TI - Greater prevalence of proposed DSM-5 nicotine use disorder compared to DSM-IV nicotine dependence in treated adolescents and young adults. AB - AIMS: Compared to DSM-IV nicotine dependence, proposed DSM-5 nicotine use disorder (NUD) would lower the threshold from three to two symptoms, and increase the number of criteria used for diagnosis from seven to 11. The impact of the proposed changes on nicotine disorder prevalence and the concurrent validity of diagnostic criteria were examined. DESIGN: Cross-sectional survey to compare DSM IV and proposed DSM-5 algorithms. SETTING AND PARTICIPANTS: Adolescent (n = 179) and young adult (n = 292) past-year cigarette users recruited from addictions treatment. MEASUREMENTS: Semi-structured clinical interview to evaluate DSM-IV nicotine dependence, and 10 of the 11 proposed DSM-5 NUD criteria; 30-day time line follow-back; and the Fagerstrom Test for Nicotine Dependence (FTND). FINDINGS: Prevalence of proposed DSM-5 NUD (two-symptom threshold) was much higher (adolescents: 68.7%, young adults: 86.0%) than DSM-IV nicotine dependence (33.0% and 59.6%, respectively), although prevalence of DSM-5 severe NUD (four symptom threshold) was similar to DSM-IV nicotine dependence. Concurrent validity analyses in both samples indicated consistent support for DSM-5 severe NUD diagnosis (four symptoms) but not for the moderate NUD (two symptoms) diagnosis, which had modest relations with only FTND score. IRT analyses indicated strong support for the new craving item, but not for the proposed interpersonal problems and hazardous use items. CONCLUSIONS: The proposed DSM-5 nicotine use disorder criteria have substantial limitations when applied to adolescents and young adults, and appear to have low concurrent validity. PMID- 22092544 TI - Peri-implant bone reactions to immediate implants placed at different levels in relation to crestal bone. Part II: a pilot study in dogs. AB - PURPOSE: The aim of the present study was to evaluate bone-to-implant contact (BIC) and bone remodeling dynamics after immediate implant placement at different levels in relation to the crestal bone with two different implant designs in beagle dogs. MATERIALS AND METHODS: The mandibular second, third and fourth premolars of six beagle dogs were extracted bilaterally and three implants were immediately placed in the hemi-arches of each dog. Randomly, three cylindrical and three tapered implants were inserted crestally (control group) or 2 mm subcrestally (test group). Both groups were treated with a minimal mucoperiosteal flap elevation approach. A gap from the buccal cortical wall to the implant was always left. Three dogs were allowed a 4-week submerged healing period and the other three an 8-week submerged healing period. The animals were sacrificed and samples were obtained. Biopsies were processed for ground sectioning. Histomorphometric analysis was carried out in order to compare BIC, de novo bone formation and bone remodeling. RESULTS: All implants osseointegrated clinically and histologically. Healing patterns examined microscopically at 4 and 8 weeks for both groups (crestal and subcrestal) yielded similar qualitative bone findings. The total BIC mean value for the crestal group was 36.48 +/- 3.4% and for the subcrestal group was 41.46 +/- 4.2%. The mean percentage of newly formed BIC was greater with the cylindrical implant design (46.06 +/- 1.09%) than with the tapered design (33.89 +/- 1.72%). There was less bone resorption in the subcrestal group (test) than crestal group (control). CONCLUSION: These findings suggest that apical positioning of the top of the implant does not jeopardize bone crest and peri-implant tissue remodeling. However, less resorption of the lingual crest may be expected when implants are placed 2 mm subcrestally. Moreover, higher BIC values were found in cylindrical implants placed subcrestally. PMID- 22092545 TI - Rejuvenation of periorbital area: treatment with an injectable nonanimal non crosslinked glycerol added hyaluronic acid preparation. AB - BACKGROUND: Therapeutic approaches to aging of the periorbital region are unique because of the delicacy of the anatomical structures and the possibility of adverse events. The synthesis of hyaluronic acid (HA) and other components responsible for skin hydration and elasticity diminish with age. OBJECTIVE: To evaluate the efficacy and safety of an injectable product containing non crosslinked HA of nonanimal origin in association with glycerol to treat aging of the periorbital region. MATERIALS AND METHODS: A pilot study in which 20 women were administered three monthly superficial intradermal injections of non crosslinked HA of nonanimal origin containing glycerol in the periorbital area. The clinical results consisted of the evaluation of three researchers and an independent evaluator and the degree of posttreatment patient satisfaction. RESULTS: An improvement of between 25% and 50% in skin brightness, texture, and turgor was observed in the periorbital area. Papules were present after each application, and hematoma was the longest lasting effect. All adverse events were reversible and well tolerated. CONCLUSION: Injections of HA of nonanimal origin, in association with glycerol, using a micropuncture technique are well tolerated and can improve skin brightness and turgor and reduce roughness in the periorbital region. PMID- 22092546 TI - In vitro study of the biological interface of Bio-Oss: implications of the experimental setup. AB - OBJECTIVES: To systematically investigate the biological interface of Bio-Oss by analysing dissolution-precipitation behaviour and osteogenic responses using in vitro experimental systems. MATERIAL AND METHODS: Different concentrations (1-100 mg/ml) of Bio-Oss were incubated in cell culture medium for 24 h before elemental concentrations for calcium, phosphorus and silicon in the medium were analysed with inductive coupled plasma-optical emission spectroscopy. Radioactive calcium 45 isotope labelling technique was used to study possible precipitation of calcium on the Bio-Oss particle. Biological interface of Bio-Oss was studied in osteogenic experiments using mineralization medium and three different sources of cells (primary mouse bone marrow stromal cells, primary rat calvarial cells and MC3T3-E1 mouse pre-osteoblast cell line). Cells were fixed and stained with Toulidine blue, von Kossa or Alizarin Red staining for confirmation of extracellular matrix mineralization. RESULTS: Elemental analysis of the cell culture medium demonstrated a significant decrease of calcium and phosphorus and a dose-dependent release of silicon to the medium after incubation with Bio-Oss. A significant decrease of calcium and phosphorus in the medium occurred even at low concentrations of Bio-Oss. Uptake of calcium on the Bio-Oss particle was confirmed with radioactive calcium-45 isotope labelling technique. In osteogenic experiments with Bio-Oss (<1 mg/ml), matrix mineralization around the Bio-Oss particles were demonstrated in all three cell types with von Kossa and Alizarin Red staining. CONCLUSION: Dissolution-precipitation reactions occur at the surface of Bio-Oss, and osteogenic responses are seen at the biological interface. The concentration of Bio-Oss is a key factor for the experimental in vitro results, and may also have implications for the clinic. PMID- 22092547 TI - Retention force of plastic clips on implant bars: a randomized controlled trial. AB - OBJECTIVES: Retention of overdentures is important for patients' satisfaction. The study tested whether the clinical performance of retentive clips made of poly ether-ether-ketone (PEEK) is superior to those made of poly-oxy-methylene (POM). METHODS: A total of 30 patients received complete dentures with round bars (SFI Bar) on two implants in a chairside technique. Two types of clip matrices (PEEK/POM) were used in a split-mouth technique. Retention forces were measured separately for both materials at baseline when the dentures were inserted and after 1, 3 and 6 months. The measurement was performed extraorally and intraorally by using a measuring stylus equipped, respectively, with an opposing matrix or bar part. Simultaneously, at each point in time the patient and the dentist judged the retention either to be good, or to be too high or too low. Statistical analysis involved performance of global non-parametric testing of dependence of retention force on time and material was performed with Brunner Langer model; non-parametric 95% confidence intervals (CIs) were calculated. RESULTS: At baseline the median force for POM matrices was 6.89N (95% CI: 6.50 8.21) and for PEEK matrices 7.17N (95% CI: 6.97-7.93). After 6 months, the retention of POM decreased to 5.53N (95% CI: 4.81-7.00) and of PEEK to 6.42N (95% CI: 5.15-7.51). The retention force changed significantly over time (P = 0.004) without differences between POM and PEEK (P = 0.135). No significant alteration of the retention force over time was measured at the bar (P = 0.289). Retention was estimated to be good with 90% at baseline and with 80% after 6 months, equally by patients and dentist. CONCLUSIONS: POM as well as PEEK material fulfills the requirements of retentive clips on round bars. PMID- 22092548 TI - Use of a special knife and blade for Mohs layers when tumor extends to the perichondrium of the ear. PMID- 22092549 TI - Excitatory amino acid transporter 2 and excitatory amino acid transporter 1 negatively regulate calcium-dependent proliferation of hippocampal neural progenitor cells and are persistently upregulated after injury. AB - Using a transgenic mouse (Mus musculus) in which nestin-expressing progenitors are labeled with enhanced green fluorescent protein, we previously characterized the expression of excitatory amino acid transporter 2 (GltI) and excitatory amino acid transporter 1 (Glast) on early neural progenitors in vivo. To address their functional role in this cell population, we manipulated their expression in P7 neurospheres isolated from the dentate gyrus. We observed that knockdown of GltI or Glast was associated with decreased bromodeoxyuridine incorporation and neurosphere formation. Moreover, we determined that both glutamate transporters regulated progenitor proliferation in a calcium-dependent and metabotropic glutamate receptor-dependent manner. To address the relevance of this in vivo, we utilized models of acquired brain injury, which are known to induce hippocampal neurogenesis. We observed that GltI and Glast were specifically upregulated in progenitors following brain injury, and that this increased expression was maintained for many weeks. Additionally, we found that recurrently injured animals with increased expression of glutamate transporters within the progenitor population were resistant to subsequent injury-induced proliferation. These findings demonstrate that GltI and Glast negatively regulate calcium-dependent proliferation in vitro and that their upregulation after injury is associated with decreased proliferation after brain trauma. PMID- 22092550 TI - Relationships among subgross anatomy, computed tomography, and histologic findings in dogs with disease localized to the pulmonary acini. AB - During computed tomography (CT), the appearance of disease involving the pulmonary acinus may be described using terms such as atelectasis, ground-glass opacity, or consolidation. These CT signs, however, have not been correlated with histologic findings in canine pulmonary disease. To facilitate interpretation of lung diseases by CT signs, our goals were to review the morphologic organization of the lung and evaluate the medical records of four dogs with different types of pulmonary acinar disease. Anatomic review focused on understanding the pulmonary acinus and the secondary pulmonary lobule; the secondary pulmonary lobule is a fundamental unit for interpretation in people. All dogs had similar CT findings of fully expanded lungs with increased attenuation and partial-to-complete obscuring of the pulmonary blood vessels. Histologic findings varied between dogs and included partial-to-complete filling of airspaces with cells or fluid, interstitial thickening, increased capillary blood volume, or a combination of these findings. Final diagnoses were hemorrhagic pneumonia, bronchiolar carcinoma, metastatic mammary adenocarcinoma, and pulmonary edema. In summary, the morphologic organization of the lungs is complex and has implications for diagnostic interpretation needing further evaluation in dogs. In this study, increased lung attenuation during CT due to disease localized to the pulmonary acini was due to the displacement of air from the lungs and not to the microscopic distribution of lesions within the pulmonary acinus. Imaging descriptors that classify diseases according to structures larger than the pulmonary acini, for example, regions of the secondary pulmonary lobule or larger, may be appropriate for dogs. PMID- 22092551 TI - Persistence of Escherichia coli in freshwater periphyton: biofilm-forming capacity as a selective advantage. AB - Recent research has shown that Escherichia coli can persist in aquatic environments, although the characteristics that contribute to their survival remain poorly understood. This study examines periphytic E. coli populations that were continuously present in three temperate freshwater lakes from June to October 2008 in numbers ranging from 2 to 2 * 10(2) CFU 100 cm(-2) . A crystal violet assay revealed that all tested periphytic E. coli isolates were superior biofilm formers and they formed, on average, 2.5 times as much biofilm as E. coli isolated from humans, 4.5 times as much biofilm as shiga-like toxin-producing E. coli, and 7.5 times as much biofilm as bovine E. coli isolates. Repetitive extragenic palindromic polymerase chain reaction (REP-PCR) DNA fingerprinting analysis demonstrated the genetically diverse nature of the periphytic isolates, with genetic similarity between strains ranging from 40% to 86%. Additionally, the role of curli fibers in biofilm formation was investigated by comparing biofilm formation with curli expression under optimal conditions, although little correlation (R(2) = 0.095, P = 0.005) was found. The high mean biofilm-forming capacity observed in E. coli isolated from the periphyton suggests that selective pressures may favor E. coli capable of forming biofilms in freshwater environments. PMID- 22092552 TI - Obesity and aspirin intolerance are risk factors for difficult-to-treat asthma in Japanese non-atopic women. AB - BACKGROUND: Asthma is a clinical syndrome characterized by variabilities in disease expression and severity. The pathophysiological mechanism underlying anti asthma treatment resistance is also assumed to be different between disease phenotypes. OBJECTIVE: To elucidate the effect of gender and atopic phenotype on the relationship between clinical factors and the risk of treatment resistance. METHODS: We compared outpatients with difficult-to-treat asthma (DTA; n = 486) in a tertiary hospital for allergic diseases in central Japan with those with controlled severe asthma (n = 621) with respect to clinical factors including body mass index (BMI) and aspirin intolerance using multivariate logistic regression analysis stratified by gender and atopic phenotype. RESULTS: When analysis was performed on the entire study populations, obesity (BMI >= 30 kg/m(2); adjusted odds ratio (OR) 1.92; 95% confidence interval (95% CI: 1.07 3.43) and aspirin intolerance (OR: 2.56, 95% CI: 1.44-4.57) were found to be the significant risk factors for DTA. However, after the stratification by gender and atopic phenotype, the association between obesity and DTA was significant only in women (OR: 2.76, 95% CI: 1.31-5.78), but not in men (OR: 1.03, 95% CI: 0.38 2.81), and only in non-atopics (OR: 4.03, 95% CI: 1.15-14.08), but not in atopics (OR: 1.54, 95% CI: 0.79-3.02). The similar gender and phenotypic differences were also observed in the association between aspirin intolerance and DTA: namely, the association was significant only in women (OR: 3.96, 95% CI: 1.84-8.50), but not in men (OR: 1.19, 95% CI: 0.46-3.05); and only in non-atopics (OR: 5.49, 95% CI: 1.98-15.19), but not in atopics (OR: 1.39, 95% CI: 0.65-2.98). CONCLUSIONS AND CLINICAL RELEVANCE: Significant associations of obesity and aspirin intolerance with DTA were observed only in women and in non-atopics. These findings suggest that a phenotype-specific approach is needed to treat patients with DTA. PMID- 22092553 TI - Influence of ultrasound or halogen light on microleakage and hardness of enamel adjacent to glass ionomer cement. AB - BACKGROUND: The use of external sources of energy may accelerate the setting rate of glass ionomer cements (GICs) allowing better initial mechanical properties. AIM: To investigate the influence of ultrasound and halogen light on the microleakage and hardness of enamel adjacent to GIC restorations, after artificial caries challenge. DESIGN: Cavities were prepared in 60 primary canines, restored with GIC, and randomly distributed into three groups: control group (CG), light group (LG) - irradiation with a halogen light-curing unit for 60s, and ultrasonic group (UG) - application of ultrasonic scaler device for 15s. All specimens were then submitted to a cariogenic challenge in a pH cycling model. Half of sample in each group were immersed in methylene blue for 4h and sectioned for dye penetration analysis. The remaining specimens were submitted to Knoop cross-sectional microhardness assessments, and mineral changes were calculated for adjacent enamel. RESULTS: Data were compared using Kruskal-Wallis test and two-way ANOVA with 5% significance. Higher dye penetration was observed for the UG (P<0.01). No significant mineral changes were observed between groups (P=0.844). CONCLUSION: The use of halogen light-curing unit does not seem to interfere with the properties of GICs, whereas the use of ultrasound can affect its marginal sealing. PMID- 22092554 TI - Satellite cell count, VO(2max) , and p38 MAPK in inactive to moderately active young men. AB - Satellite cells (SCs) are responsible for muscle repair following strenuous exercise or injury. SC responses to intervention have been studied, but most studies do not discuss or take into account the substantial variability in SC number among young individuals. We hypothesized that an active lifestyle reflected in higher VO(2max) may be associated with greater SC number. As training alters basal p38-mitogen-activated protein kinase (MAPK) activity, which is associated with SC proliferation, SC count may also correlate with this stress signaling kinase. Muscle biopsies from vastus lateralis of eight male participants were analyzed for fiber type, myogenin, and p38/phospho-p38 MAPK using SDS-PAGE and Western blotting. Immunofluorescence was used to detect Pax7(+) SCs. Two weeks following the biopsy, subjects underwent an incremental treadmill test to determine VO(2max) . A strong positive correlation (P = 0.0087) was found between the number of Pax7(+) nuclei and VO(2max) . Pax7(+) cell number correlated negatively with phospho-p38/p38 MAPK (P = 0.0006), but had no correlation with fiber type or myogenin. SC number is proportional to VO(2max) , and hence it can be postulated that higher levels of physical activity activate SC proliferation but not fusion, underlining the relevance of exercise in stimulating SC pool size even without injury. PMID- 22092555 TI - Annexin-1-deficient mice exhibit spontaneous airway hyperresponsiveness and exacerbated allergen-specific antibody responses in a mouse model of asthma. AB - BACKGROUND: Glucocorticoids are the mainstream drugs used in the treatment and control of inflammatory diseases such as asthma. Annexin-1 (ANXA1) is an anti inflammatory protein which has been described as an endogenous protein responsible for some anti-inflammatory glucocorticoid effects. Previous studies have identified its importance in other immune diseases such as rheumatoid arthritis and cystic fibrosis. ANXA1-deficient ((-/-)) mice are Th2 biased, and ANXA1 N-terminus peptide exhibits anti-inflammatory activity in a rat model of pulmonary inflammation. OBJECTIVE: ANXA1 protein is found in bronchoalveolar lavage fluid from asthmatics. However, the function of ANXA1 in the pathological development of allergy or asthma is unclear. Thus, in this study we intended to examine the effect of ANXA1 deficiency on allergen-specific antibody responses and airway responses to methacholine (Mch). METHODS: ANXA1(-/-) mice were sensitized with ovalbumin (OVA) and challenged with aerosolized OVA. Airway resistance, lung compliance and enhanced pause (PenH) were measured in naive, sensitized and saline or allergen-challenged wild-type (WT) and ANXA1(-/-) mice. Total and allergen-specific antibodies were measured in the serum. RESULTS: We show that allergen-specific and total IgE, IgG2a and IgG2b levels were significantly higher in ANXA1(-/-) mice. Furthermore, naive ANXA1(-/-) mice displayed higher airway hypersensitivity to inhaled Mch, and significant differences were also observed in allergen-sensitized and allergen-challenged ANXA1(-/-) mice compared with WT mice. CONCLUSIONS: In conclusion, ANXA1(-/-) mice possess multiple features characteristic to allergic asthma, such as airway hyperresponsiveness and enhanced antibody responses, suggesting that ANXA1 plays a critical regulatory role in the development of asthma. CLINICAL RELEVANCE: We postulate that ANXA1 is an important regulatory factor in the development of allergic disease and dysregulation of its expression can lead to pathological changes which may affect disease progression. PMID- 22092556 TI - Distribution of the entodiniomorphid ciliate Troglocorys cava Tokiwa, Modry, Ito, Pomajbikova, Petrzelkova, & Imai, , (Entodiniomorphida: Blepharocorythidae) in wild and captive chimpanzees. AB - Trophozoites of Troglocorys cava were detected in all but one of the wild chimpanzee populations from Rubondo Island (Tanzania), with a prevalence ranging between 20% and 78%. However, the ciliate was absent in all captive groups. Prevalence appeared to increase with the number of sequential samples taken from a particular individual and reached 95.5% in wild individuals sampled at least 4 times. PMID- 22092557 TI - An insight into the ligand-receptor interactions involved in the translocation of pathogens across blood-brain barrier. AB - Traversal of pathogen across the blood-brain barrier (BBB) is an essential step for central nervous system (CNS) invasion. Pathogen traversal can occur paracellularly, transcellularly, and/or in infected phagocytes (Trojan horse mechanism). To trigger the translocation processes, mainly through paracellular and transcellular ways, interactions between protein molecules of pathogen and BBB are inevitable. Simply, it takes two to tango: both host receptors and pathogen ligands. Underlying molecular basis of BBB translocation of various pathogens has been revealed in the last decade, and a plethora of experimental data on protein-protein interactions has been created. This review compiles these data and should give insights into the ligand-receptor interactions that occur during BBB translocation. Further, it sheds light on cell signaling events triggered in response to ligand-receptor interaction. Understanding of the molecular principles of pathogen-host interactions that are involved in traversal of the BBB should contribute to develop new vaccine and drug strategies to prevent CNS infections. PMID- 22092558 TI - The human macrophage sodium channel NaV1.5 regulates mycobacteria processing through organelle polarization and localized calcium oscillations. AB - Phagocytosis and intracellular processing of mycobacteria by macrophages are complex cellular processes that require spatial and temporal coordination of particle uptake, organelle movement, activation of signaling pathways, and channel-mediated ionic flux. Recent work demonstrated that human macrophage NaV1.5, an intracellular voltage-gated sodium channel expressed on late endosomes, enhances endosomal acidification and phagocytosis. Here, using bacillus Camille-Guerin (BCG) as a model of mycobacterial infection, we examined how this channel regulates phagocytosis and phagosome maturation in human macrophages. Knockdown of NaV1.5 reduced high capacity uptake of labeled BCG. BCG containing, NaV1.5-expressing cells demonstrated localization of NaV1.5 and Rab-7 positive endosomes and mitochondria to periphagosome regions that was not observed in NaV1.5-deficient cells. Knockdown of the channel reduced the initial calcium response following bacterial challenge and prevented the generation of prolonged and localized calcium oscillations during phagosome maturation. Inhibition of the mitochondrial Na(+) /Ca(2+) exchanger also prevented prolonged calcium oscillations during phagosome maturation. These results suggest that NaV1.5 and mitochondrial-dependent calcium signaling regulate mycobacteria phagocytosis and phagosome maturation in human macrophages through spatial temporal coordination of calcium signaling within a unique subcellular region. PMID- 22092559 TI - Novel roles for autotransporter adhesin AatA of avian pathogenic Escherichia coli: colonization during infection and cell aggregation. AB - Systemic infections in avian species caused by avian pathogenic Escherichia coli (APEC) are economically devastating to poultry industries worldwide. To unravel factors possibly involved in APEC pathogenicity, suppression subtractive hybridization was applied, leading to the identification of a putative APEC autotransporter adhesin gene aatA in our previous study. In this study, pathogenic mechanism of AatA was further determined. A deletion mutant of aatA was constructed in the APEC DE205B, which results in the reduced capacity to adhere to DF-1 cells, defective virulence in vivo, and decreased colonization capacity in lung during the systemic infection compared with the wild-type strain. Furthermore, these capacities were restored in the complementation strains. These results indicated that AatA makes a significant contribution to APEC virulence through bacterial adherence to host tissues in vivo and in vitro. In addition, aggregation assays for strain AAEC189 expressing aatA indicated that AatA mediates cell aggregation and settling of cells. However, this cell aggregation is blocked by Type I fimbriae. This study illustrates the first examination of the role of AatA in aggregation and systemic infection. PMID- 22092560 TI - Permissivity of fish cell lines to three Chlamydia-related bacteria: Waddlia chondrophila, Estrella lausannensis and Parachlamydia acanthamoebae. AB - Epitheliocystis is an infectious disease affecting gills and skin of various freshwater and marine fishes, associated with high mortality and reduced growth of survivors. Candidatus Piscichlamydia salmonis and Clavochlamydia salmonicola have recently been identified as aetiological agents of epitheliocystis in Atlantic Salmon. In addition, several other members of the Chlamydiales order have been identified in other fish species. To clarify the pathogenicity of Chlamydia-like organisms towards fishes, we investigated the permissivity of two fish cell lines, EPC-175 (Fathead Minnow) and RTG-2 (rainbow trout) to three Chlamydia-related bacteria: Waddlia chondrophila, Parachlamydia acanthamoebae and Estrella lausannensis. Quantitative PCR and immunofluorescence demonstrated that W. chondrophila and, to a lesser extent, E. lausannensis were able to replicate in the two cell lines tested. Waddlia chondrophila multiplied rapidly in its host cell and a strong cytopathic effect was observed. During E. lausannensis infection, we observed a limited replication of the bacteria not followed by host cell lysis. Very limited replication of P. acanthamoebae was observed in both cell lines tested. Given its high infectivity and cytopathic effect towards fish cell lines, W. chondrophila represents the most interesting Chlamydia-related bacteria to be used to develop an in vivo model of epitheliocystis disease in fishes. PMID- 22092561 TI - Bacterial translocation in cirrhosis is not caused by an abnormal small bowel gut microbiota. AB - Sepsis is common in liver cirrhosis, and animal studies have shown the gut to be the principal source of infection, through bacterial overgrowth and translocation in the small bowel. A total of 33 patients were recruited into this study, 10 without cirrhosis and 23 with cirrhotic liver disease. Six distal duodenal biopsies were obtained and snap frozen for RNA and DNA extraction, or frozen for FISH. Peripheral venous bloods were obtained from 30 patients, including 17 chronic liver disease patients. Samples were analysed by real-time PCR, to assess total bacteria, bifidobacteria, bacteroides, enterobacteria, staphylococci, streptococci, lactobacilli, enterococci, Helicobacter pylori and moraxella, as well as TNF-alpha, IL-8 and IL-18. There was no evidence of bacterial overgrowth with respect to any of the individual bacterial groups, with the exception of enterococci, which were present in higher numbers in cirrhotic patients (P = 0.04). There were no significant differences in any of the cytokines compared to the controls. The small intestinal mucosal microbiota in cirrhotic patients was qualitatively and quantitatively normal, and this shifts the focus of disease aetiology to factors that reduce gut integrity, failure of mechanisms to remove translocating bacteria, or the large bowel as the source of sepsis. PMID- 22092562 TI - Protective mechanism of curcumin against Vibrio vulnificus infection. AB - Curcumin, a natural polyphenolic flavonoid extracted from the rhizome of Curcuma longa L., has many beneficial biological activities. However, there are relatively few reports of the effects of curcumin on pathogen infections. This study examined the effect of curcumin on a Vibrio vulnificus infection. The cytotoxicity of V. vulnificus to HeLa cells was significantly inhibited by curcumin (at 10 or 30 MUM). To further examine the inhibitory mechanism of curcumin against V. vulnificus-mediated cytotoxicity, the level of bacterial growth, bacterial motility, cell adhesion, RTX toxin expression and host cell reactions were evaluated. Curcumin inhibited V. vulnificus growth in HI broth. Curcumin inhibited both bacterial adhesion and RTX toxin binding to the host cells, which can be considered the major protective mechanisms for the decrease in V. vulnificus cytotoxicity. Curcumin also inhibited host cell rounding and actin aggregation, which are the early features of cell death caused by V. vulnificus. In addition, curcumin decreased the V. vulnificus-induced NF-kappaB translocation in HeLa cells. Finally, curcumin protected mice from V. vulnificus induced septicemia. In conclusion, curcumin may be an alternative antimicrobial agent against fatal bacterial infections. PMID- 22092563 TI - Cryptococcus neoformans suppresses the activation of bone marrow-derived dendritic cells stimulated with its own DNA, but not with DNA from other fungi. AB - DNA from Cryptococcus neoformans activates bone marrow-derived dendritic cells (BM-DCs) in a TLR9-dependent manner. In this study, we examined the effect of the culture supernatants of C. neoformans on the activation of BM-DCs caused by its own DNA. C. neoformans supernatants suppressed IL-12p40, IL-6 production and CD40 expression by BM-DCs stimulated with its own DNA, but not with CpG-ODN and DNA from Candida albicans, Saccharomyces cerevisiae or Escherichia coli. In a confocal microscopic analysis, C. neoformans DNA was colocalized with LAMP-1, a late endosomal marker, and TLR9. The culture supernatants did not show any apparent suppression of these responses. In a luciferase reporter assay, C. neoformans supernatants inhibited NFkappaB activation caused by its own DNA. These inhibitory activities were attenuated by treatment with heat or trypsin. These results indicate that C. neoformans secrete certain proteinous molecules that suppress the activation of BM-DCs caused by its own DNA. PMID- 22092564 TI - Molecular typing of Bordetella parapertussis isolates circulating in Pakistan. AB - Although a whole-cell pertussis vaccine was introduced in Pakistan in 1980, little is known about the pertussis prevalence and circulating strains in Pakistan. The aim of this study was to analyze Bordetella parapertussis isolates circulating between 2005 and 2009 in Pakistan and to compare them with those found in other countries during different periods. A total of 59 (7.35%) B. parapertussis isolates from 802 subjects (median age, 3 years) from Pakistan, with pertussis-like symptoms were investigated. We carried out genotyping and DNA microarray analyses on these isolates and compared them with some international isolates of B. parapertussis. We found that the allele for pertactin (prn) found in strains studied from Pakistan was identical to the predominant type found in Europe. We showed that B. parapertussis isolates circulating in Pakistan are part of the same pulsed-field gel electrophoresis group to those circulating in Finland during the period of 1982-2007. Finally, microarray analysis confirmed that the isolates collected in Pakistan, were quite similar to international strains. Overall, these results confirm that B. parapertussis is extremely monomorphic. The high isolation rate of B. parapertussis (7.35%) compared to Bordetella pertussis (0.5%) may suggest that the whole-cell vaccine used in Pakistan is effective against B. pertussis (0.5% infections detected), but much less so against B. parapertussis. PMID- 22092565 TI - Induction of prostaglandin E(2) and interleukin-6 in gingival fibroblasts by oral biofilms. AB - Polymicrobial oral biofilms attaching on tooth surfaces can trigger inflammatory responses by the neighbouring tooth-supporting periodontal tissues. An excessive inflammatory response can cause destruction of the periodontal tissues, including the alveolar bone, thus resulting in periodontitis. Mediators of inflammation, such as prostaglandin E(2) (PGE(2) ) and interleukin-6, are primary regulators of alveolar bone destruction in periodontitis. The present study aimed to comparatively investigate the effects of in vitro supragingival and subgingival biofilms, on the regulation of PGE(2) and interleukin-6 in human gingival fibroblasts. The cells were challenged with culture supernatants of the two biofilms for 6 h. Cyclo-oxygenase (COX)-2, an enzyme responsible for the conversion of PGE(2) , and interleukin-6 gene expression were analysed by quantitative real-time PCR. The production of PGE(2) and interleukin-6 by the cells was analysed by ELISA. While the supragingival biofilm did not induce significant changes, the subgingival biofilm caused an 8.6- and 2.9-fold enhancement of COX-2 and interleukin-6 gene expression, respectively, and a 72.5- and 1.5-fold enhancement of PGE(2) and interleukin-6 production, respectively. In conclusion, subgingival biofilms are potent inducers of PGE(2) in gingival fibroblasts, providing further mechanistic insights into the association of subgingival biofilms with bone resorption periodontitis. PMID- 22092566 TI - Immunoreactive proteins of Campylobacter concisus, an emergent intestinal pathogen. AB - Campylobacter concisus is an emerging pathogen of the human gastrointestinal tract. Recently, a significantly higher prevalence of C. concisus DNA and higher levels of antibodies specific to C. concisus was detected in children with Crohn's disease when compared with controls. The aim of this study was to identify C. concisus immunoreactive antigens. Proteins from C. concisus were separated using two-dimensional gel electrophoresis, and sera from 10 C. concisus positive children with Crohn's disease were employed for immunoprobing. The patients' sera reacted with 69 spots, which corresponded to 31 proteins identified by mass spectrometry. The proteins were functionally classified as involved in chemotaxis, signal transduction, flagellar motility, surface binding and membrane protein assembly. Although the individual patients' sera reacted to different sets of proteins, common antigens that were recognized by all patients were flagellin B, ATP synthase F1 alpha subunit, and outer membrane protein 18. Cross-reactivity between proteins of the Campylobacter genus was tested using patients' sera absorbed with Campylobacter showae, Campylobacter jejuni and Campylobacter ureolyticus. Most of the C. concisus immunoreactive proteins identified in this study showed cross-reactivity with other species except for three antigens. In conclusion, this study has identified C. concisus proteins that are immunoreactive within patients with Crohn's disease. PMID- 22092567 TI - Monophosphoryl lipid A induced innate immune responses via TLR4 to enhance clearance of nontypeable Haemophilus influenzae and Moraxella catarrhalis from the nasopharynx in mice. AB - Acute otitis media (AOM) is one of the most common infectious diseases in children. Nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, Gram-negative bacteria, are considered major pathogens of AOM and respiratory tract infections. In this study, we used monophosphoryl lipid A (MPL) as a Toll like receptor (TLR4) agonist to induce innate immune responses before challenge with NTHi and M. catarrhalis to enhance bacterial clearance from the nasopharynx. Mice were intranasally administered 40, 10, or 1 MUg of MPL and challenged with NTHi and M. catarrhalis 12 and 24 h later. At 6 and 12 h after the bacterial challenge, the mice were killed and nasal washes were collected. The numbers of NTHi, M. catarrhalis, and inflammatory cells were quantitated. Inoculation of MPL produced a significant reduction in the number of bacteria recovered from the nasopharynx at 6 and/or 12 h after the bacterial challenge, when compared with control mice. The effect was dose dependent. MPL inoculation also induced the early accumulation of neutrophils in the nasopharynx after exposure to bacteria. MPL is effective for eliciting clearance of both NTHi and M. catarrhalis from the nasopharynx. These results indicate the possibility of a new strategy against Gram-negative bacterial infection that involves the stimulation of the innate immune system by TLR4 agonists such as MPL. PMID- 22092568 TI - Up-regulation of human bradykinin B1 receptor by secreted components of Pseudomonas aeruginosa via a NF-kappaB pathway in epithelial cells. AB - Pulmonary epithelial cells produce neutrophil chemotactic activity in response to pathogenic bacterial infections, resulting in neutrophil migration to infection sites. Elicited neutrophils in the inflamed tissues were found to be dependent on bradykinin B1 receptor (B1R), which shows high affinity for the active metabolites derived from bradykinin. Thus, the up-regulation of bradykinin and B1R expression represents an important host defense response against invading microbes such as Pseudomonas aeruginosa. However, the effect of P. aeruginosa on the expression of B1R remains unclear, while P. aeruginosa infection is known to stimulate the production of bradykinin. Here, we report that human B1R (hB1R) transcription is up-regulated in host cells co-cultured with P. aeruginosa. Components secreted from P. aeruginosa play a major role in the up-regulation, and the secretion of the components is not controlled by either type III secretion system or quorum sensing. Moreover, the B1R induction is mediated by a NF-kappaB signaling pathway in human lung epithelial cells. Taken together, this study demonstrates that P. aeruginosa is capable of up-regulating hB1R expression via the NF-kappaB signaling pathway. PMID- 22092569 TI - Viral and bacterial abundance and production in the Western Pacific Ocean and the relation to other oceanic realms. AB - We completed a transect through the Western Pacific Warm Pool to examine how environmental variables may influence viral and bacterial abundance and production rates in this globally important oceanic region. Of the variables analyzed, viral abundance and production had the most significant relationship to bacterial cell abundance: viral parameters were not significantly correlated to the measured environmental variables, including temperature. Bacterial production rates were significantly correlated to temperature in open ocean waters, but not in waters close to land masses. Analyses of 16S rRNA gene by pyrosequencing indicated only minor changes in eubacterial community structure across the transect, with alpha-proteobacteria dominating all sampled populations. Diversity within the prokaryotic community did not correlate directly with viral abundance or activity. Comparisons to two other ocean-scale transects (> 8000 km of open ocean in total) in the Atlantic Ocean indicated that correlations between viral and bacterial abundance and production relative to environmental variables are regime dependent. In particular, correlations to temperature showed remarkable differences across the three transects. Collectively, our observations suggest that seemingly similar oceanic regions may have very different microbial community responses to environmental variables. Our observations and analyses demonstrate that ocean-scale generalizations may not apply in the case of viral ecology. PMID- 22092570 TI - A possible melanoma discrimination index based on hyperspectral data: a pilot study. AB - BACKGROUND: Early detection and proper excision of the primary lesions of malignant melanoma (MM) are crucial for reducing melanoma-related deaths. To support the early detection of melanoma, automated melanoma screening systems have been extensively studied and developed. In this article, we present a hyperspectral melanoma screening system and propose a possible melanoma discrimination index derived from the characteristics of the pigment molecules in the skin, both of which have been derived from hyperspectral data (HSD). METHODS: The index expresses the disordered nature of each lesion including variegation in color based on variation in spectral information obtained from each lesion. Performance of the index in discriminating melanomas from other pigmented skin lesions has been studied in five cases of melanoma (41 HSD sets), one case of Spitz nevus (13 HSD sets), 10 cases of seborrheic keratosis (78 HSD sets), three cases of basal cell carcinoma (16 HSD sets), and nine cases of melanocytic nevus (21 HSD sets), obtained from patients and volunteers, all of whom were Japanese. RESULTS: Performance of the index, which reflects the disordered nature of a lesion, discriminates melanomas with a sensitivity of 90%, a specificity of 84%, and an area under the receiver operating characteristic curve of 0.93, on resubstitution. CONCLUSION: An objective melanoma discrimination index at a molecular pigmentary level, derived from HSD, has been proposed, and its performance evaluated. This index was highly successful in discriminating MM from non-melanoma, although the statistical population was small. PMID- 22092571 TI - Hydrogen-rich water attenuates experimental periodontitis in a rat model. AB - AIM: Reactive oxygen species (ROS) contribute to the development of periodontitis. As molecular hydrogen can act as a scavenger of ROS, we examined the effects of treatment with hydrogen-rich water on a rat model of periodontitis. MATERIAL & METHODS: A ligature was placed around the maxillary molars for 4 weeks to induce periodontitis, and the animals were given drinking water with or without hydrogen-rich water. RESULTS: The rats with periodontitis which were treated with pure water showed a time-dependent increase in serum ROS level. Compared with the rats without periodontitis, the periodontitis-induced rats which were given pure water also showed polymorphonuclear leucocyte infiltration and alveolar bone loss at 4 weeks. Hydrogen-rich water intake inhibited an increase in serum ROS level and lowered expression of 8 hydroxydeoxyguanosine and nitrotyrosine in the periodontal tissue at 4 weeks. Such conditions prevented polymorphonuclear leucocyte infiltration and osteoclast differentiation following periodontitis progression. Furthermore, inflammatory signalling pathways, such as mitogen-activated protein kinases, were less activated in periodontal lesions from hydrogen-rich water-treated rats as compared with pure water-treated rats. CONCLUSION: Consuming hydrogen-rich water might be beneficial in suppressing periodontitis progression by decreasing gingival oxidative stress. PMID- 22092572 TI - Enhancing disaster management by mapping disaster proneness and preparedness. AB - The focus of most disaster management programmes is to deploy resources-physical and human-from outside the disaster zone. This activity can produce a delay in disaster mitigation and recovery efforts, and a consequent loss of human lives and economic resources. It may be possible to expedite recovery and prevent loss of life by mapping out disaster proneness and the availability of resources in advance. This study proposes the development of two indices to do so. The Indian census data of 2001 is used to develop a methodology for creating one index on disaster proneness and one on resourcefulness for administrative units (tehsils). Findings reveal that tehsil residents face an elevated risk of disaster and that they are also grossly under-prepared for such events. The proposed indices can be used to map regional service provision facilities and to assist authorities in evaluating immediate, intermediate, and long-term disaster recovery needs and resource requirements. PMID- 22092573 TI - Differential gene expression in planktonic and biofilm cells of multiple antibiotic-resistant Salmonella Typhimurium and Staphylococcus aureus. AB - This study was designed to evaluate gene expression patterns of the planktonic and biofilm cells of Staphylococcus aureus and Salmonella Typhimurium in trypticase soy broth adjusted to pH 5.5 and pH 7.3. The planktonic and biofilm cells of multiple antibiotic-resistant S. aureus (S. aureus(R) ) and S. Typhimurium (S. Typhimurium(R) ) were more resistant to beta-lactams than those of antibiotic-susceptible S. aureus (S. aureus(S) ) and S. Typhimurium (S. Typhimurium(S) ) at pH 5.5 and pH 7.3. The relative gene expression levels of norB, norC, and mdeA genes were increased by 7.0-, 4.7-, and 4.6-fold, respectively, in the biofilm cells of S. aureus(S) grown at pH 7.3, while norB, norC, mdeA, sec, seg, sei, sel, sem, sen, and seo genes were stable in the biofilm cells of S. aureus(R) . This study provides useful information for understanding gene expression patterns in the planktonic and biofilm cells of antibiotic-resistance pathogens exposed to acidic stress. PMID- 22092574 TI - Retrospective analysis of survival rates and marginal bone loss on short implants in the mandible. AB - OBJECTIVES: Short implants have become an interesting alternative to bone augmentation in dental implantology. Design of shorter implants and longer surveillance times are a current research issue. The goal of this study was to show the survival rates of short implants below 9 mm in the partly edentulous mandibular premolar and molar regions with fixed prosthetics. Marginal vertical and 2D bone loss was evaluated additionally. Different implant designs are orientationally evaluated. MATERIAL AND METHODS: A total of 247 dental implants with fixed prosthetics (crowns and bridges) in the premolar and molar region of the mandible were evaluated; 47 implants were 9 mm or shorter. Patient data were evaluated to acquire implant survival rates, implant diameter, gender and age. Panoramic X-rays were analysed for marginal bone loss. RESULTS: Average surveillance time was 1327 days. Cumulative survival rate (CSR) of short implants was 98% (1 implants lost) compared to 94% in the longer implants group without significance. Thirty-five of the short implants were Astratech (0 losses) and 12 were Camlog Screw Line Promote Plus (1 loss). Early vertical and two-dimensional marginal bone loss was not significantly different in short and regular length implant group with an average of 0.6 mm and 0.7 mm(2) in short implants over the observation period. CONCLUSIONS: Within the limitations of this study, we conclude that short implants with a length of 9 mm or less have equal survival rates compared with longer implants over the observation period of 1-3 years. PMID- 22092576 TI - Centella asiatica extracts modulate hydrogen peroxide-induced senescence in human dermal fibroblasts. AB - Centella asiatica (C. asiatica) is a pharmacological plant in South Asia. It has been demonstrated that C. asiatica extracts containing various pentacyclic triterpenes exert healing effects, especially wound healing and collagen synthesis in skin. However, there are few studies on the effect of C. asiatica extracts on stress-induced premature senescence (SIPS). To determine whether H(2) O(2) -induced senescence is affected by C. asiatica extracts, we performed senescence analysis on cultured human dermal fibroblasts (HDFs). We also analysed whole gene expression level using microarrays and showed that 39 mRNAs are differentially expressed in H(2) O(2) -induced HDFs with and without treatment with C. asiatica extracts. These genes regulate apoptosis, gene silencing, cell growth, transcription, senescence, DNA replication and the spindle checkpoint. Differential expression of FOXM1, E2F2, MCM2, GDF15 and BHLHB2 was confirmed using semi-quantitative PCR. In addition, C. asiatica extracts rescued the H(2) O(2) -induced repression of replication in HDFs. Therefore, the findings presented here suggest that C. asiatica extracts might regulate SIPS by preventing repression of DNA replication and mitosis-related gene expression. PMID- 22092577 TI - Thymic stromal lymphopoietin exerts antimicrobial activities. AB - Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine expressed by epithelial cells and reported to be involved in allergic diseases and atopic eczema. The presence of several predicted alpha-helical regions in TSPL, a structure characterizing many classical antimicrobial peptides (AMPs), prompted us to investigate whether TSLP exerts antimicrobial activities. Recombinant human TSLP exerted antimicrobial activity, particularly against Gram-negative bacteria. Using synthetic overlapping peptide 20-mers of TSLP, it was demonstrated that the antimicrobial effect is primarily mediated by the C-terminal region of the protein. MKK34 (MKKRRKRKVTTNKCLEQVSQLQGLWRRFNRPLLK), a peptide spanning a C terminal alpha-helical region in TSLP, showed potent antimicrobial activities, in physiological salt conditions and in the presence of human plasma. Fluorescent studies of peptide-treated bacteria, electron microscopy and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of the classical AMP LL-37. Moreover, TSLP was degraded into multiple fragments by staphylococcal V8 proteinase. One major antimicrobial degradation fragment was found to encompass the C-terminal antimicrobial region defined by the MKK34 peptide. We here describe a novel antimicrobial role for TSLP. The antimicrobial activity is primarily mediated by the C-terminal part of the protein. In combination with the previously known cytokine function of TSLP, our result indicates dual functions of the molecule and a previously unknown role in host defense. PMID- 22092578 TI - Human keratinocytes express AIM2 and respond to dsDNA with IL-1beta secretion. AB - Keratinocytes have been recognized to actively participate in the skin immune response. It has been shown that keratinocytes express all components that are necessary to form the NLRP3 inflammasome complex including the adapter protein ASC and caspase-1. In this study, we investigated the presence and activity of the recently identified absent in melanoma 2 (AIM2) inflammasome in human keratinocytes. We were able to show that an AIM2 inflammasome is active in human keratinocytes. IL-1 production by keratinocytes plays a pivotal role in inflammatory processes in the skin. Activation of the AIM2 inflammasome in keratinocytes represents another potential trigger factor for the development and maintenance of inflammatory skin diseases. PMID- 22092575 TI - The itchy scalp--scratching for an explanation. AB - Scalp pruritus is a common complaint that is considered a diagnostically and therapeutically challenging situation. Scalp skin has a unique neural structure that contains densely innervated hair follicles and dermal vasculature. In spite of the recent advances in our understanding of itch pathophysiology, scalp itching has not been studied as yet. In this review, we summarize the current knowledge on the neurobiology of scalp and hair follicles as well as itch mediators and provide a putative mechanism for scalp itch with special emphasis on neuroanatomy and pathophysiology. PMID- 22092579 TI - Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy? AB - Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma. PMID- 22092580 TI - A novel mutation of the glomulin gene in an Italian family with autosomal dominant cutaneous glomuvenous malformations. AB - Glomuvenous malformations (GVM) are hamartomas characterized histologically by glomus cells, which should be distinguished from glomus tumors. Familial GVM are rare, often present as multiple lesions, and exhibit familial aggregation, with autosomal dominant transmission. GVM are caused by mutations of the glomulin (GLMN) gene on chromosome 1p21-p22. Their development is thought to follow the 'two-hit' hypothesis, with a somatic mutation required in addition to the inherited germline mutation. We describe a novel GLMN mutation in an Italian family with GVM in which some members present with the less commonly observed phenotype of solitary lesions. A second somatic 'hit' mutation in GLMN was not discovered in our family. We further provide histological, immunohistochemical and electron microscopic data exhibiting the classic features of GVM. The diagnosis of GVM is critical because of distinction from venous malformations and blue rubber bleb nevus syndrome, which may demonstrate clinical similarities but require different treatment. PMID- 22092581 TI - Fitness consequences of social network position in a wild population of forked fungus beetles (Bolitotherus cornutus). AB - Social networks describe the pattern of intraspecific interactions within a population. An individual's position in a social network often is expected to influence its fitness, but only a few studies have examined this relationship in natural populations. We investigated the fitness consequences of network position in a wild beetle population. Copulation success of male beetles positively covaried with strength (a measure of network centrality) and negatively covaried with clustering coefficient (CC) (a measure of cliquishness). Further analysis using mediation path models suggested that the activity level of individuals drove the relationships between strength and fitness almost entirely. In contrast, selection on CC was not explained by individual behaviours. Although our data suggest that social network position can experience strong sexual selection, it is also clear that the relationships between fitness and some network metrics merely reflect variation in individual-level behaviours. PMID- 22092582 TI - Errors in basophil enumeration with 3 veterinary hematology systems and observations on occurrence of basophils in dogs. AB - BACKGROUND: Most automated hematology analyzers cannot detect canine or feline basophils. However, many veterinary laboratories continue to report basophils as part of the automated 5-part differential leukocyte count for dogs and cats. OBJECTIVES: The study objectives were to evaluate the performance of the Sysmex XT-2000iV, Advia 2120, and CELL-DYN 3500 hematology analyzers in detecting basophils using blood from dogs, cats, and rabbits with basophilia and to investigate the concurrence of basophilia and other hematologic changes, sex, and breed in dogs. METHODS: One or more of the 3 hematology analyzers was used to analyze 11 canine blood samples with prominent basophilia (>= 5%) based on a manual differential count. In addition, samples from 2 cats and 4 rabbits with basophilia were analyzed with the Advia 2120. Leukocyte cytograms were inspected for the likely location of basophil cell clusters. In a retrospective study of canine patients, reports of hematologic results that included a manual leukocyte differential count were identified using the laboratory information system and examined for the occurrence of basophilia and other hematologic changes, sex, and breed of the dogs. RESULTS: Canine basophils were not detected by the Sysmex XT 2000iV or CELL-DYN 3500 analyzers, and neither canine nor feline basophils were detected by the Advia 2120. The Advia was able to detect basophils in rabbits. On the Sysmex cytogram canine basophils were found slightly above or together with neutrophils. On the Advia Perox cytogram canine basophils were located in upper part of the lymphocyte box and in the area of large unstained cells (LUC). Dogs with marked basophilia often had concurrent eosinophilia, and basophilia may be found more frequently in Rottweiler dogs than in other breeds. In 5 dogs with marked basophilia and without eosinophilia, marked thrombocytosis and anemia were noted. CONCLUSIONS: Canine basophils were not detected by these automated hematology analyzers, and careful analysis of instrument graphical displays or increased LUC (Advia) may guide the need to examine a blood smear for basophils. PMID- 22092583 TI - Surgical-site infections and routes of bacterial transfer: which ones are most plausible? AB - BACKGROUND: Surgical-site infections (SSIs) are an unfortunate consequence of cutaneous surgery. Their incidence can be a significant problem for patients and surgeons. Most SSIs are presumed to originate from the patient and operating room staff. OBJECTIVES: To review the potential routes of iatrogenic bacterial transfer during cutaneous surgery. METHODS: A review of the medical literature. CONCLUSIONS: Potential routes of bacterial transfer during surgery include respiratory droplets and nuclei, skin scales carried on air currents, direct contact with the surgical team's skin, and contaminated fomites. The route with the most significant potential for iatrogenic bacterial transfer is direct physical contact. Strategies that minimize contact with infected fomites and with the surgical team would probably have the best chances of reducing the incidence of SSIs. PMID- 22092584 TI - Risk of bias of animal studies on regenerative procedures for periodontal and peri-implant bone defects - a systematic review. AB - OBJECTIVES: (1) To assess the risk of bias of studies in which animal models were used for investigating regenerative therapies for periodontal and peri-implant defects. (2) To investigate changes in risk of bias by comparing samples drawn from two different publication periods. MATERIAL & METHODS: We searched the PubMed and LILACS electronic databases, independently and in duplicate, for randomized and controlled trials published from 1998 to 2000 and from 2008 to 2010. Hand searching included search of 10 dental journals, in the issues published between August 2008 and August 2010. Studies on non-human primates and canines were included. We assessed independently and in triplicate the risk of bias with reference to a six-item checklist based on the Cochrane Collaboration's tool for assessing the risk of bias and information about formal sample size calculation. RESULTS: One hundred and seven studies were included in the review. Checklist items were poorly reported in the studies selected, and therefore for most of the studies, the risk of bias was unclear. CONCLUSION: As a result of the unclear risk of bias of animal studies in periodontal and peri-implant treatments, it is difficult to determine the accuracy of treatment effect estimates. There is a need for standardization of reporting procedures on animal experiments. PMID- 22092585 TI - Randomized trials for the treatment of burning mouth syndrome: an evidence-based review of the literature. AB - Burning mouth syndrome (BMS) is defined as a chronic pain condition, characterized symptomatically by a generalized or localized burning sensation in the oral cavity. Various drugs have been used in attempting to treat BMS, but there is insufficient evidence to show the effect of any effective treatment. The aim of this review was to assess the effectiveness of therapies for BMS. Randomized controlled trials (RCTs) enrolling patients with a diagnosis of BMS were identified by searching Pubmed and Scoppus databases. The methodological quality of included studies was assessed on the basis of the method of allocation concealment, blindness of the study, loss of participants, size sample, and outcome concealment. A total of 12 relevant articles were analyzed. Therapies that used capsaicin, alpha-lipoic acid (ALA), and clonazepam were those that showed more reduction in symptoms of BMS. However, many studies of therapeutic interventions in BMS lack consistency in their results, because they use in their methodology, sample and a relatively short time of therapy and often do not provide a follow-up of patients treated. Thus, future studies are required to establish the treatment for patients suffering from this chronic and painful syndrome. PMID- 22092586 TI - Factors influencing transfer accuracy of cone beam CT-derived template-based implant placement. AB - OBJECTIVES: The aim of the present investigation was the analysis of the factors presumptively affecting the accuracy outcome of cone-beam computed tomography (CBCT)-derived laboratory-based surgical guides for implant placement in partially edentulous patients. MATERIALS AND METHODS: In 52 partially edentulous patients a total of 132 implants were placed following CBCT diagnostics with the aid of laboratory-fabricated, tooth-borne templates. Based on the image fusion technique measurements were done to calculate linear and angular deviations between virtually planned and placed implants. The implant sites were stratified according to four factors that presumably may influence the transfer accuracy: (i) type of arch (maxilla/mandible), (ii) kind of template (single-tooth gap/interrupted dental arch/shortened dental arch/reduced residual dentition), (iii) surgical technique (flapless/open flap), (iv) number of sleeve-guided site preparation steps (fully guided placement/freehand placement/freehand final drilling). The data were analyzed using analysis of variance and the Bonferroni test. RESULTS: The transfer accuracy of shoulder level, apex level, and angulation was similar for maxilla and mandible as well as for flapless and open flap approach. The differences were small in magnitude and reached no or only a borderline statistical significance. At implant sites in the reduced residual dentition group, the discrepancies were more pronounced than in the single-tooth gap group, whereas no significant differences could be determined between free ending templates in the shortened dental arch and bilateral anchored templates in the interrupted dental arch. Implant placement through the guide allowed a more accurate implementation of the virtual plan to the surgical site than freehand insertion or freehand final drilling. CONCLUSION: CBCT-derived laboratory-based surgical templates enabled an implant placement in the cancellous maxilla as well as flapless procedures without compromising the transfer accuracy. The number and distribution of the remaining teeth as well as the number of sleeve-guided implant site preparation steps influenced the extent of deviation that can be achieved in partial edentulism. PMID- 22092587 TI - Biomechanical evaluation of a microstructured zirconia implant by a removal torque comparison with a standard Ti-SLA implant. AB - OBJECTIVES: The purpose of this study was to evaluate the biomechanical bone tissue response to novel microstructured zirconia implants in comparison to sandblasted and acid-etched (SLA) titanium implants through the analysis of removal torque (RTQ) measurements. MATERIALS AND METHODS: Ti-SLA implants with a sandblasted, large-grit and acid-etched surface were compared with zirconia implants with an acid-etched surface. All implants had the same shape, a diameter of 4.1 mm and a length of 10 mm. A total of 136 implants were placed in the maxillae of 17 miniature pigs. Six animals were sacrificed after both 4 and 8 weeks and five animals were sacrificed after 12 weeks, thus providing a total of 102 implants for RTQ testing (34 implants were reserved for future histological analysis). The RTQ analysis was successfully performed, using a mixed model regression with P-values calculated using the nonparametric Brunner-Langer method, on 100 of the 102 implants, two were excluded from the analysis. RESULTS: The adjusted mean RTQ values for Ti-SLA implants were 131 Ncm (95% CI: 107-155) at 4 weeks, 128 Ncm (108-148) Ncm at 8 weeks, and 180 Ncm (153-207 Ncm) at 12 weeks of healing, whereas RTQ values for the zirconia implants were 110 Ncm (86 134), 97 Ncm (76-118) and 147 Ncm (121-174) at the corresponding time intervals. A comparison of the implant materials resulted in P-values of P = 0.114 at 4 weeks, P = 0.034 at 8 weeks and P = 0.105 at 12 weeks (significance set at P < 0.05). CONCLUSIONS: Within the limits of the present study, it could be confirmed that the biomechanical bone-tissue response of the investigated zirconia implants is non-inferior to that of the well-documented, roughened titanium surface, at each time point, within the set tolerance. There were no statistically significant differences between the two materials after a healing period of 4 and 12 weeks. The RTQ values of both implant types increased significantly from the 8 week to the 12-week time point. PMID- 22092588 TI - Characterization of an UV- and VIS-absorbing, purpurogallin-derived secondary pigment new to algae and highly abundant in Mesotaenium berggrenii (Zygnematophyceae, Chlorophyta), an extremophyte living on glaciers. AB - Mesotaenium berggrenii is one of few autotrophs that thrive on bare glacier surfaces in alpine and polar regions. This extremophilic alga produces high amounts of a brownish vacuolar pigment, whose chemical constitution and ecological function is largely unknown until now. Field material was harvested to isolate and characterize this pigment. Its tannin nature was determined by photometric methods, and the structure determination was carried out by means of HPLC-MS and 1D- and 2D-NMR spectroscopy. The main constituent turned out to be purpurogallin carboxylic acid-6-O-beta-d-glucopyranoside. This is the first report of such a phenolic compound in this group of algae. Because of its broad absorption capacities of harmful UV and excessive VIS radiation, this secondary metabolite seems to play an important role for the survival of this alga at exposed sites. Attributes and abundances of the purpurogallins found in M. berggrenii strongly suggest that they are of principal ecophysiological relevance like analogous protective pigments of other extremophilic microorganisms. To prove that M. berggrenii is a true psychrophile, photosynthesis measurements at ambient conditions were carried out. Sequencing of the 18S rRNA gene of this alpine species and of its arctic relative, the filamentous Ancylonema nordenskioldii, underlined their distinct taxonomic position within the Zygnematophyceae. PMID- 22092590 TI - Age-related changes in the guinea pig auditory cortex: relationship with brainstem changes and comparison with tone-induced hearing loss. AB - Elderly people often show degraded hearing performance and have difficulties in understanding speech, particularly in noisy environments. Although loss in peripheral hearing sensitivity is an important factor in explaining these low performances, central alterations also have an impact but their exact contributions remained unclear. In this study, we focus on the functional effects of aging on auditory cortex responses. Neuronal discharges and local field potentials were recorded in the auditory cortex of aged guinea pigs (> 3 years), and several parameters characterizing the processing of auditory information were quantified: the acoustic thresholds, response strength, latency and duration of the response, and breadth of tuning. Several of these parameters were also quantified from auditory brainstem responses collected from the same animals, and recordings obtained from a population of animals with trauma-induced hearing loss were also included in this study. The results showed that aging and acoustic trauma reduced the response strength at both brainstem and cortical levels, and increased the response latencies more at the cortical level than at the brainstem level. In addition to the brainstem hearing loss, aging induced a 'cortical hearing loss' as judged by additive changes in the threshold and frequency response seen in the cortex. It also increased the duration of neural responses and reduced the receptive field bandwidth, effects that were not found in traumatized animals. These effects substantiate the notion that presbycusis involves both peripheral hearing loss and biological aging in the central auditory system. PMID- 22092589 TI - Clinical and radiographic evaluation of NobelActive(TM) dental implants. AB - OBJECTIVES: To conduct a randomised controlled trial to evaluate the short-term clinical and radiographic efficacy of the NobelActiveTM system and to evaluate the relative importance of achieving primary stability at placement. MATERIALS AND METHODS: A total of 32 subjects were recruited and, using a split-mouth design, the NobelActive(TM) implant was compared with a contralaterally matched Branemark implant. Both implants were placed in a single surgical procedure into healed sites using a one-stage protocol and reviewed at monthly intervals. NobelActive(TM) implants were functionally loaded with provisional restorations at 1 month and all implants were restored with final crowns 3 months post-implant placement. The implant was assessed using peak insertion torque values, resonance frequency analysis (RFA), clinical parameters, digital subtraction radiography, and cone beam computed tomography. RESULTS: The insertion torque was significantly greater for the NobelActive(TM) implant group (P = 0.02), although no observable difference in RFA values were found. Preliminary results of 6 months follow-up suggest comparable clinical and radiographic healing responses between the test and control implants. Within the limits of the sample population, the survival rates were lower with the test implants, although this difference was not statistically significant. CONCLUSIONS: The NobelActive(TM) implant system requires higher insertion torques and can also achieve greater primary stability compared with a control implant system. Short-term survival and marginal bone levels of NobelActive(TM) and control implants are comparable, although the NobelActive(TM) implant system appeared to be more technique sensitive. PMID- 22092591 TI - Mutational analysis of YgfZ, a folate-dependent protein implicated in iron/sulphur cluster metabolism. AB - Proteins of the YgfZ family occur in all domains of life and are characterized by the conserved dodecapeptide motif KGC[Y/F]-x-GQE-x(3) -[R/K]. YgfZ proteins are known to participate in assembly or repair of iron/sulphur clusters, and to require folate for biological activity, but their mechanism of action is unknown. To assess the importance of individual residues in the conserved motif, Escherichia coli Ygf Z was expressed from a plasmid in a DeltaygfZ strain and subjected to alanine-scanning mutagenesis. The impacts on YgfZ functionality were evaluated by assays of growth and of the in vivo activity of the iron/sulphur enzyme MiaB, which modifies tRNA. By these criteria, the motif's tyrosine residue (Y229) had a detectable influence but only the cysteine residue (C228) was critical, for only the C228A mutant failed to complement the growth and MiaB activity phenotypes of the DeltaygfZ strain. Immunoblots confirmed that the latter result was not simply because of a low level of the C228A mutant protein. Collectively, these data demonstrate a pivotal role for the Ygf Z motif's cysteine residue and a subsidiary one for the adjacent tyrosine, and help formulate a hypothesis about the folate requirement of Ygf Z proteins. PMID- 22092592 TI - Completeness of reporting of radiation therapy planning, dose, and delivery in veterinary radiation oncology manuscripts from 2005 to 2010. AB - Surrounding a shift toward evidence-based medicine and widespread adoption of reporting guidelines such as the Consolidated Standards of Reporting Trials (CONSORT) statement, there has been a growing body of literature evaluating the quality of reporting in human and veterinary medicine. These reviews have consistently demonstrated the presence of substantive deficiencies in completeness of reporting. The purpose of this study was to assess the current status of reporting in veterinary radiation oncology manuscripts in regards to treatment planning methods, dose, and delivery and to introduce a set of reporting guidelines to serve as a standard for future reporting. Forty-six veterinary radiation oncology manuscripts published between 2005 and 2010 were evaluated for reporting of 50 items pertaining to patient data, treatment planning, radiation dose, delivery of therapy, quality assurance, and adjunctive therapy. A mean of 40% of checklist items were reported in a given manuscript (range = 8-75%). Only 9/50 (18%) checklist items were reported in > or = 80% manuscripts. The completeness of reporting was best in regards to a statement of prescription radiation protocol (91-98% reported) and worst in regards to specification of absorbed dose within target volumes and surrounding normal tissues (0-6% reported). No manuscripts met the current International Commission of Radiation Units and Measurements (ICRU) dose specification recommendations. Incomplete reporting may stem from the predominance of retrospective manuscripts and the variability of protocols and equipment in veterinary radiation oncology. Adoption of reporting guidelines as outlined in this study is recommended to improve the quality of reporting in veterinary radiation oncology. PMID- 22092593 TI - Effect of intense pulsed light on rat skin. AB - BACKGROUND: Intense pulsed light (IPL) is widely used in treating skin conditions and has been reported to increase collagen and elastic fibers without damaging the epidermis. OBJECTIVE: To evaluate the effect of variation in the number of passes and intervals of IPL treatments on photorejuvenation in rats. MATERIALS AND METHODS: Groups of two rats each were exposed to two or four passes of an IPL source using a fluence of 30 J/cm(2) and a cut-off filter of 560 nm at 1- or 3 week intervals. The collagen and elastic fiber content in stained tissue biopsies and the thickness of the collagen fibers of IPL-irradiated and unexposed skin regions were compared. RESULTS: Collagen distribution and collagen fiber diameter was in IPL-irradiated than in control regions. The number of passes did not significantly affect the collagen fiber thickness, but the collagen fibers from the 3-week-interval groups were thicker than those of the 1-week-interval groups (p < .001). CONCLUSION: IPL increased dermal collagen fibers and collagen fiber diameter, suggesting efficacy in photorejuvenation and wrinkle reduction. PMID- 22092594 TI - Low neonatal Toll-like receptor 4-mediated interleukin-10 production is associated with subsequent atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) and respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are common diseases during early life. Impaired Th1-cell polarizing Toll-like receptor (TLR) responses play an important role in the pathogenesis of both diseases. Neonatal TLR-mediated production of Th1-type cytokines is decreased at birth, but rapidly increases during the first month of life. OBJECTIVE: To determine whether decreased TLR-mediated production of Th1-polarizing cytokines, at the age of 1 month is associated with subsequent AD or RSV LRTI. METHODS: A prospective healthy birth cohort study was performed. Whole blood concentrations of innate immune cells and TLR-mediated cytokine responses were measured at the age of 1 month in 291 neonates. AD was determined by a physician questionnaire at the age of 1 year and RSV LRTI was defined as parent-reported respiratory symptoms and presence of RSV RNA in a nose-throat specimen. RESULTS: Of participating neonates, 45 (15%) developed AD and 41 (14%) developed RSV LRTI. Risks of AD and RSV LRTI were not associated (chi(2) , P = 1.00). AD was associated with decreased concentrations of basophils (7.6 vs. 14.0 * 10(6) /mL, P = 0.002) and plasmacytoid dendritic cells (17.0 vs. 20.5 * 10(6) /mL, P = 0.04), increased concentrations of NK-cells (79.7 vs. 45.1 * 10(6) /mL, P = 0.03), and twofold lower TLR4-mediated IL-10 production (P = 0.001). In contrast, RSV LRTI was associated neither with neonatal concentrations of innate immune cells, nor with TLR-mediated TNF-alpha, IL-12p70, IL-10 or IFN-alpha production. CONCLUSIONS AND CLINICAL RELEVANCE: Atopic dermatitis, but not RSV LRTI, is associated with distinct pre-symptomatic differences in the innate immune system. We hypothesize that decreased neonatal IL-10-mediated immune regulation during early life might play a causal role in the initiation of AD. PMID- 22092595 TI - Human leucocyte antigen-G: expression and function in airway allergic disease. AB - Human leucocyte antigen-G (HLA-G) is a non-classical HLA class I molecule demonstrated originally in placental trophoblast cells. Recognition of the importance of HLA-G to the maternal immune accommodation of the semi-allogeneic fetus has led to investigations of its role in the suppression of immune responses and induction of tolerance. More recently, HLA-G has been shown to have increased expression in several immunological diseases including asthma and allergic rhinitis. The focus of this review is the potential role of HLA-G in immunological airway diseases. PMID- 22092597 TI - Effects of Coxiella burnetii on MAPKinases phosphorylation. AB - Q fever is a disease caused by Coxiella burnetii, an obligate intracellular bacterium. Acute Q fever is characterized by efficient immune response, whereas chronic Q fever is characterized by dysregulated immune response as demonstrated by the lack of granulomas, the failure of C. burnetii to induce lymphoproliferation, and interferon-gamma production. The mitogen-activated protein kinase (MAPK) signaling pathway plays crucial roles in innate immune responses and control of bacterial infections. However, its role in Q fever has not been addressed. First, we investigated the activation of MAPKs p38, c-jun N terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) 1/2 in murine macrophages stimulated with C. burnetii. Coxiella burnetii NM phase I (virulent) and NM phase II (avirulent) induced the activation of JNK and ERK1/2. Avirulent C. burnetii activate p38, whereas C. burnetii did not induce the phosphorylation of p38. Second, the level of p38 activation was studied in Q fever patients. We found that p38 was activated in monocyte-derived macrophages from healthy donors and patients with acute Q fever in response to a potent agonist such as lipopolysaccharide. Interestingly, p38 was not activated in patients with active chronic Q fever and was activated in patients with cured chronic Q fever. These results suggest that the determination of p38 activation may serve as a tool for measuring Q fever activity. PMID- 22092596 TI - Knowledge of paediatricians regarding child oral health. AB - BACKGROUND: In dentistry, clinical practice is directed towards attitudes that promote oral health and the paediatricians occupy a privileged position in this process. AIM: To assess the knowledge and attitudes of paediatricians in relation to the oral health of their patients. DESIGN: A cross-sectional study was carried out at the Institute of Integrative Medicine Professor Fernando Figueira, Recife, Brazil. A total of 182 paediatricians participated by filling out a questionnaire. RESULTS: A total of 63.9% believed the first visit to the dentist should occur before the child completes 1 year of life. Moreover, 67.8% considered their knowledge on oral health to be insufficient. Approximately 78% of the paediatricians diagnosed caries through an analysis of cavities. Only 29.9% always recommended fluoride dentifrice. The term 'fluorosis' was unknown by 48.3% of the respondents. Concerning pacifiers, 32.6% did not allow it and 66.9% did not either recommend it or restrict it. A total of 83.4% classified the oral health content in their medical education as either nonexistent or deficient; this figure remained high (72.4%) in relation to residency. CONCLUSIONS: It is important to develop oral health information programmes to paediatricians. Information on oral health should be included in medical curricula and residency. PMID- 22092598 TI - Ciliate ingestion and digestion: flow cytometric measurements and regrowth of a digestion-resistant Campylobacter jejuni. AB - We measured ingestion and digestion rates of the pathogenic bacterium Campylobacter jejuni by a freshwater ciliate Colpoda sp. to determine whether Campylobacter is able to resist protist digestion. Campylobacter and the nonpathogenic bacterium Pseudomonas putida LH1 were labeled with a 5 chloromethylfluorescein diacetate, which fluoresces in intact and active cells but fades when exposed to low pH environments, such as protistan food vacuoles. Ingestion and digestion rates were measured via flow cytometry as the change in ciliate fluorescence over time, which corresponded to the quantity of intracellular bacteria. The rate of Campylobacter ingestion exceeded the digestion rate. Ciliates retained labeled Campylobacter 5 h after ingestion was stopped. In contrast, ciliates grazing upon P. putida returned to baseline fluorescence within 5 h, indicating that P. putida were completely digested. The ability of intracellular Campylobacter to remain viable after ingestion was tested by sorting individual ciliates and bacterial cells into Campylobacter selective media. Campylobacter growth occurred in 15% (+/- 5 SE) of wells seeded with highly fluorescent ciliates, whereas only 4% (+/- 1) of wells seeded with free-living Campylobacter exhibited growth. A key advantage of this approach is that it is rapid and should be applicable to other phagocytotis studies. PMID- 22092599 TI - Incorporation of plant residue-derived carbon into the microeukaryotic community in a rice field soil revealed by DNA stable-isotope probing. AB - The microbial decomposition of plant residue is a central part of the carbon cycle in soil ecosystems. Here, we explored the microeukaryotic community responsible for the uptake of plant residue carbon in a rice field soil through DNA-based stable-isotope probing (SIP) using dried rice callus labelled with (13) C as a model substrate. Molecular fingerprinting with PCR-DGGE showed that the total eukaryotic community in soil under drained (upland) conditions distinctly changed within 3 days after the callus was applied and stable thereafter. The predominant group of eukaryotes that incorporated callus carbon were fungi affiliated with the Mucoromycotina (Mortierella), Ascomycota (Galactomyces, Eleutherascus, Gibberella and Fusarium) and Zoopagomycotina (Syncephalis). 'Fungus-like' protists such as Pythium (stramenopiles) and Polymyxa (Cercozoa) were also involved in carbon flow from the callus. Some of these fungi and 'fungus-like' protists took up soil organic matter with time, which suggested a priming effect of the callus on the eukaryotic community. Our results demonstrated the usefulness of SIP not only to trace the carbon flow from fresh organic matter but also to study the effect of fresh organic matter on the utilization of soil organic matter by the microbial community. PMID- 22092600 TI - Where's the naevus? Inter-operator variability in the localization of melanocytic lesion border. AB - BACKGROUND: The first step in the analysis of a dermatoscopically imaged melanocytic lesion is segmentation--informally, isolating those points in the image belonging to the lesion from those belonging to the surrounding non lesional skin. Although typically studied in the context of automated analysis, segmentation is a necessary step even for human operators who plan to evaluate quantitative features of a lesion (such as diameter or asymmetry). METHODS: In a double blind evaluation of the segmentation of 77 digital dermatoscopic images, we observed a significant inter-operator variability. RESULTS: The area of the disagreement region was on average 15.28% of the area of the lesion itself, and in 10% of the cases it was more than 28%. More experienced dermatologists showed greater agreement among themselves than with less experienced dermatologists, and a slight tendency toward 'tighter' segmentations. CONCLUSION: The evaluation methodology addresses a number of crucial difficulties encountered in previous studies and may be of independent interest. Our results underscore the necessity of taking into account inter-operator variability in large epidemiological studies, in particular those involving less experienced dermatologists, and of striving toward techniques allowing greater standardization and replicability in the evaluation of the fundamental visual parameters of lesions. PMID- 22092601 TI - The development of doping use in high-level cycling: from team-organized doping to advances in the fight against doping. AB - In 1998, the Festina scandal at the Tour de France provided the first proof of widespread doping in professional cycling. This doping scandal marked the end of team-organized doping in professional cycling and ushered in a new period marked by the increasing implementation of anti-doping measures. This article evaluates the impact of the anti-doping rules and tests instituted since the Festina scandal. We adopt a psychosocial approach to analyze the organization of doping and the development of doping attitudes and practices in high-level cycling. Sixteen cyclists were interviewed, of which eight were young, current cyclists and eight were former cyclists who became professionals before the Festina scandal. Our results show that although the fight against doping in the last decade has reduced doping use in high-level cycling, anti-doping measures have also had unexpected effects. The fight against doping in cycling is not over. PMID- 22092602 TI - Direct visualization of the interaction between pilin and exopolysaccharides of Myxococcus xanthus with eGFP-fused PilA protein. AB - Type IV pili (TFP) and exopolysaccharides (EPS) are important components for social behaviors in Myxococcus xanthus, including gliding motility and fruiting body formation. Although specific interactions between TFP and EPS have been proposed, there have as yet been no direct observations of these interactions under native conditions. In this study, we found that a truncated PilA protein (PilACt) containing only the C-terminal domain (amino acids 32-208) is sufficient for EPS binding in vitro. Furthermore, an enhanced green fluorescent protein (eGFP) and PilACt fusion protein were constructed and used to label the native EPS in M. xanthus. Under confocal laser scanning microscope, the eGFP-PilACt bound fruiting bodies, trail structures and biofilms exhibited similar patterns as the wheat germ agglutinin lectin-labeled EPS structures. This study showed that eGFP-PilACt fusion protein was able efficiently to label the EPS of M. xanthus, providing evidence for the first time of the direct interaction between the PilA protein and EPS under native conditions. PMID- 22092603 TI - Inequalities in exposure and awareness of flood risk in England and Wales. AB - This paper explores the environmental inequalities of living in the floodplains of England and Wales and the differences in flood awareness of those 'at risk'. An area comparison is made between an etic, objective flood risk exposure, and an emic, subjective perception of that risk by social class. In all areas except the Midlands, the working classes were more likely to reside in the floodplains; the greatest exposure inequality is seen in the North East and Anglian regions. Flood awareness in the Anglian regions was much lower than average, but there were no significant class differences. In the Thames region, despite equal flood risk exposure between classes, the most deprived displayed the least awareness of flood risk. In the North East, inequalities in the distribution of flood risk exposure accompanied inequalities in perception, resulting in the least aware and most deprived experiencing the greatest flood risk. PMID- 22092604 TI - Periodontal disease: a new factor associated with the presence of multiple complex coronary lesions. AB - BACKGROUND AND AIM: Periodontal disease, including bone loss, is thought to be involved in coronary artery disease. Multiple complex coronary lesions relate to multifocal destabilization of coronary plaques. We investigated whether bone loss could be associated with the presence of multiple complex coronary lesions. METHODS: This cross-sectional study included 150 patients with recent myocardial infarction (<1 month). Multiple complex coronary lesions were determined at coronary angiography. A panoramic dental X-ray including bone loss >50% was performed. Patients with no or simple complex lesions were compared to patients with multiple complex lesions. RESULTS: Over 20% of patients had multiple complex coronary lesions. Patients with multiple complex lesion were less likely to be women and more likely to have multivessel disease or elevated C-reactive protein (CRP) than patients with no or single complex lesion. Bone loss >50% tended to be more frequent in patients with multiple complex lesions (p = 0.063). In multivariate analysis, multivessel disease, gender and CRP were associated with multiple complex lesion. Bone loss >50% increased the risk of multiple complex lesion. CONCLUSION: Bone loss was associated with complex multiple coronary lesions, beyond systemic inflammation. These findings may bear important clinical implications for the prevention and treatment of coronary artery disease. PMID- 22092605 TI - A comparison between laser-doppler imaging and colorimetry in the assessment of scarring: "a pilot study". AB - BACKGROUND: This cross-sectional pilot-study investigated the reproducibility of the LDI (Moor-LDI-B2; Moor Instruments) and the chromameter (Minolta chromameter CR-300) when used in scar assessment. METHODS: Twenty-seven scars in 14 subjects were included between January and June 2003. One observer performed two times both measurements with 10 min apart. The intra-observer agreement is quantified by means of the intra-class correlations (ICC) and the standard errors of measurement (SEM) for both the LDI and the chromameter. RESULTS: Ignoring one outlier, the ICC of the LDI = 0.856 and the SEM = 34.56. The chromameter shows a better reproducibility with an ICC of 0.93 and a SEM of 0.79. CONCLUSION: This pilot-study with a limited number of measurements shows a moderate reproducibility of the LDI compared to the chromameter measurements, in the assessment of respectively flux and redness in scars. PMID- 22092606 TI - Periodontal health status and bacteraemia from daily oral activities: systematic review/meta-analysis. AB - AIM: The aim of this study was to investigate the robustness of the observations on the influence of oral hygiene, gingival and periodontal status on the development of bacteraemia from everyday oral activities (B-EOA), analysing its prevalence, duration, magnitude and bacterial diversity. MATERIAL AND METHODS: This systematic review/meta-analysis complies with PRISMA reporting guidelines. MEDLINE-PubMed, the Cochrane Library and Embase were explored for detecting studies on B-EOA. RESULTS: There were 290 potentially eligible articles, of which 12 article on B-EOA fulfilled the inclusion criteria and were processed for data extraction (seven on toothbrushing, one on dental flossing and four on chewing). Evaluating the influence of plaque and gingival indices on the prevalence of bacteraemia following toothbrushing, the pooled odds ratios were 2.61 [95% confidence interval (CI) = 1.45-4.69] and 2.77 (95% CI = 1.50-5.11), respectively. None of five studies on bacteraemia following dental flossing and chewing revealed a statistically significant association between oral hygiene, gingival or periodontal status and the development of bacteraemia. CONCLUSIONS: Meta-analysis showed that plaque accumulation and gingival inflammation scores significantly increased the prevalence of bacteraemia following toothbrushing. However, systematic review showed no relationship between oral hygiene, gingival and periodontal status and the development of B-chewing, and there is no evidence that gingival and periodontal health status affects B-flossing. PMID- 22092607 TI - Enteropathogenic bacteria in dogs and cats: diagnosis, epidemiology, treatment, and control. AB - This report offers a consensus opinion on the diagnosis, epidemiology, treatment, and control of the primary enteropathogenic bacteria in dogs and cats, with an emphasis on Clostridium difficile, Clostridium perfringens, Campylobacter spp., Salmonella spp., and Escherichia coli associated with granulomatous colitis in Boxers. Veterinarians are challenged when attempting to diagnose animals with suspected bacterial-associated diarrhea because well-scrutinized practice guidelines that provide objective recommendations for implementing fecal testing are lacking. This problem is compounded by similar isolation rates for putative bacterial enteropathogens in animals with and without diarrhea, and by the lack of consensus among veterinary diagnostic laboratories as to which diagnostic assays should be utilized. Most bacterial enteropathogens are associated with self-limiting diarrhea, and injudicious administration of antimicrobials could be more harmful than beneficial. Salmonella and Campylobacter are well-documented zoonoses, but antimicrobial administration is not routinely advocated in uncomplicated cases and supportive therapy is recommended. Basic practices of isolation, use of appropriate protective equipment, and proper cleaning and disinfection are the mainstays of control. Handwashing with soap and water is preferred over use of alcohol-based hand sanitizers because spores of C. difficile and C. perfringens are alcohol-resistant, but susceptible to bleach (1:10 to 1:20 dilution of regular household bleach) and accelerated hydrogen peroxide. The implementation of practice guidelines in combination with the integration of validated molecular-based testing and conventional testing is pivotal if we are to optimize the identification and management of enteropathogenic bacteria in dogs and cats. PMID- 22092608 TI - Diagnosis, treatment, control, and prevention of infections caused by Rhodococcus equi in foals. AB - Rhodococcus equi, a gram-positive facultative intracellular pathogen, is one of the most common causes of pneumonia in foals. Although R. equi can be cultured from the environment of virtually all horse farms, the clinical disease in foals is endemic at some farms, sporadic at others, and unrecognized at many. On farms where the disease is endemic, costs associated with morbidity and mortality attributable to R. equi may be very high. The purpose of this consensus statement is to provide recommendations regarding the diagnosis, treatment, control, and prevention of infections caused by R. equi in foals. PMID- 22092609 TI - Rhodococcus equi: clinical manifestations, virulence, and immunity. AB - Pneumonia is a major cause of disease and death in foals. Rhodococcus equi, a gram-positive facultative intracellular pathogen, is a common cause of pneumonia in foals. This article reviews the clinical manifestations of infection caused by R. equi in foals and summarizes current knowledge regarding mechanisms of virulence of, and immunity to, R. equi. A complementary consensus statement providing recommendations for the diagnosis, treatment, control, and prevention of infections caused by R. equi in foals can be found in the same issue of the Journal. PMID- 22092610 TI - Hypoxic ischemic encephalopathy--what can we learn from humans? AB - Hypoxic ischemic encephalopathy (HIE) is a condition that occurs in both human newborns and foals. The condition is the subject of extensive current research in human infants, but there have been no direct studies of HIE in foals, and hence, knowledge of the condition has been extrapolated from studies in humans and other animal models. The purpose of this review article is to highlight the most up-to date and relevant research in the human field, and discuss how this potentially might have an impact in the management of foals with HIE. PMID- 22092611 TI - Sensitivity and specificity of canine pancreas-specific lipase (cPL) and other markers for pancreatitis in 70 dogs with and without histopathologic evidence of pancreatitis. AB - BACKGROUND: Pancreatitis is a common disorder in dogs for which the antemortem diagnosis remains challenging. OBJECTIVES: To compare the sensitivity and specificity of serum markers for pancreatitis in dogs with histopathologic evidence of pancreatitis or lack thereof. ANIMALS: Seventy dogs necropsied for a variety of reasons in which the pancreas was removed within 4 hours of euthanasia and serological markers were evaluated within 24 hours of death. METHODS: Prospective study: Serum was analyzed for amylase and lipase activities, and concentrations of canine trypsin-like immunoreactivity (cTLI) and canine pancreas specific lipase (cPL). Serial transverse sections of the pancreas were made every 2 cm throughout the entire pancreas and reviewed using a semiquantitative histopathologic grading scheme. RESULTS: The sensitivity for the Spec cPL (cutoff value 400 MUg/L) was 21 and 71% in dogs with mild (n = 56) or moderate-severe pancreatitis (n = 7), and 43 and 71% (cutoff value 200 MUg/L), respectively. The sensitivity for the cTLI, serum amylase, and lipase in dogs with mild or moderate severe pancreatitis was 30 and 29%; 7 and 14%; and 54 and 71%, respectively. The specificity for the Spec cPL based on 7 normal pancreata was 100 and 86% (cutoff value 400 and 200 MUg/L, respectively), whereas the specificity for the cTLI, serum amylase, and lipase activity was 100, 100, and 43%, respectively. CONCLUSION AND CLINICAL IMPORTANCE: The Spec cPL demonstrated the best overall performance characteristics (sensitivity and specificity) compared to other serum markers for diagnosing histopathologic lesions of pancreatitis in dogs. PMID- 22092612 TI - Normal dogs treated with famotidine for 14 days have only transient increases in serum gastrin concentrations. AB - BACKGROUND: In people, serum gastrin concentrations increase in response to administration of H(2) receptor antagonists, but the effect of famotidine administration on serum gastrin concentrations has not been evaluated in dogs. OBJECTIVES: To determine if serum gastrin concentrations increase in response to 14 days of famotidine treatment and the time needed to return to baseline after discontinuation of famotidine; define stability of gastrin in samples held at room temperature. ANIMALS: Eleven healthy dogs were included in part A (famotidine treatment) and 7 healthy dogs in Part B (serum gastrin stability). In part A, famotidine (0.5 mg/kg p.o. q12h) was administered for 14 days. Fasting blood samples were collected on days 0, 3, 7, 11, 14, 16, 18, 20, and 22. In part B, blood was collected after a 12-hour fast. Gastrin concentrations in serum samples held at room temperature for <=30 minutes after sampling were compared to concentrations in samples held at room temperature for 150 minutes after sampling. RESULTS: Serum gastrin concentrations increased by day 3 of famotidine administration and returned to baseline concentrations in all dogs by day 14 despite continued famotidine administration. Serum gastrin concentrations were lower (20% mean decrease; P = .0005) in samples held at room temperature for 150 minutes. CONCLUSIONS AND CLINICAL IMPORTANCE: After 14 days of famotidine administration, clinically healthy dogs have normal serum gastrin concentrations. In a dog with clinical features consistent with gastrinoma, chronic famotidine administration is unlikely to contribute to increases in serum gastrin concentrations. PMID- 22092613 TI - Utility of endoscopic biopsies of the duodenum and ileum for diagnosis of inflammatory bowel disease and small cell lymphoma in cats. AB - BACKGROUND: Endoscopic duodenal biopsies are relatively convenient, minimally invasive tests for infiltrative intestinal disorders of cats. Ileal endoscopic biopsies might not be performed because of technical difficulty and effort required to prepare the colon. It is not known whether or not histopathology of feline duodenal and ileal biopsies for detection of inflammatory bowel disease (IBD) and small cell lymphoma (SC-LSA) provides comparable results. OBJECTIVES: To evaluate the agreement between endoscopic biopsies of duodenum and ileum in cats with IBD and SC-LSA. ANIMALS: Seventy client-owned cats with gastrointestinal disease and adequate duodenal and ileal tissue biopsies obtained endoscopically. METHODS: Retrospective study: Search of medical records of cats with enteropathy and endoscopy. Samples were blinded and re-evaluated by single pathologist (JM) for quality, number of biopsies, and diagnosis according to WSAVA standards. Agreement of IBD and SC-LSA diagnoses among biopsy sites assessed using Cohen's Kappa. RESULTS: Eighteen of 70 cats (26%) were diagnosed with SC-LSA in duodenum, ileum, or both. Of these 18 cats, 7 (39%) were diagnosed with only duodenal SC-LSA, 8 (44%) were diagnosed with only ileal SC-LSA, and 3 (17%) had SC-LSA in both duodenum and ileum. There was poor agreement on diagnosis between duodenal and ileal biopsies (kappa = 0.23). CONCLUSIONS AND CLINICAL IMPORTANCE: Although review by a single pathologist remains a limitation of this study, results suggest that there is a population of cats in which diagnosis of SC-LSA can be found only by evaluation of ileal biopsies. Clinicians should consider performing both upper and lower GI endoscopic biopsies in cats with infiltrative small bowel disease. PMID- 22092614 TI - The presence of antiphospholipid antibodies in healthy Bernese Mountain Dogs. AB - BACKGROUND: The role of antiphospholipid antibodies in the prolonged activated partial thromboplastin time (aPTT) previously identified in healthy Bernese Mountain Dogs remains unknown. In people, an isolated prolonged aPTT without evidence of bleeding might be because of a thrombophilic condition caused by antiphospholipid antibodies. OBJECTIVE: To examine if prolonged aPTT in healthy Bernese Mountain Dogs is because of antiphospholipid antibodies. ANIMALS: Twenty two healthy Bernese Mountain Dogs and 10 healthy adult dogs of various breeds. METHODS: Prospective case control study. Healthy Bernese Moutain Dogs were examined twice over 6 months. Dogs were investigated for the presence of lupus anticoagulants and anticardiolipin (aCL) antibodies by the use of multiple aPTT tests with low and high lupus anticoagulant sensitivities, a mixing study, and an ELISA test for aCL antibody optical density to detect solid phase antiphospholipid antibodies. RESULTS: In all, 15 of 22 healthy Bernese Mountain Dogs were positive for lupus anticoagulants. The Bernese Mountain Dogs had markedly higher levels of aCL antibodies compared with the control dogs (P = .006). In all, 7 of 21 of the Bernese Mountain Dogs were positive for both lupus anticoagulants and aCL antibodies, whereas 4 of 21 Bernese Mountain Dogs were negative for both. CONCLUSIONS AND CLINICAL IMPORTANCE: Lupus anticoagulants and aCL antibodies could be the cause of prolonged aPTT in healthy Bernese Mountain Dogs. The importance of the antiphospholipid antibodies in the dogs remains unknown. PMID- 22092615 TI - Detection of Bartonella henselae IgM in serum of experimentally infected and naturally exposed cats. AB - BACKGROUND: Results of Bartonella henselae blood culture, polymerase chain reaction (PCR) assay on blood, or IgG antibody assays do not always correlate with the presence or absence of clinical disease in cats, and B. henselae IgG antibodies in serum do not always correlate with bacteremia. However, little is known concerning Bartonella spp. IgM antibodies in naturally exposed cats. HYPOTHESIS: Bartonella spp. IgM antibodies in serum are associated with fever, stomatitis, and bacteremia based on PCR assay results in experimentally infected or client-owned cats. ANIMALS: Stored sera from cats experimentally infected with B. henselae by exposure to Ctenocephalides felis, client-owned cats with and without fever, and client-owned cats with and without stomatitis were studied. METHODS: A Bartonella spp. IgM ELISA was titrated with samples from experimentally infected cats and then test sera from client-owned cats were assayed. Associations among IgM ELISA results, clinical findings, and bacteremia as defined by Bartonella spp. PCR assay were assessed. RESULTS: All experimentally infected cats developed Bartonella spp. IgM antibodies. Bartonella spp. IgM antibody assay results were not always in agreement with PCR assay results in client-owned cats (60%). Bartonella spp. DNA in blood, IgM antibodies, and IgG antibodies were not associated with the presence of fever or stomatitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Because Bartonella spp. IgM antibodies as measured by this assay were not associated with fever or stomatitis and were not always in agreement with PCR assay results, there appears to be little need for assessing individual client-owned cats for this antibody class alone. PMID- 22092616 TI - Randomized, placebo controlled study of the effect of propentofylline on survival time and quality of life of cats with feline infectious peritonitis. AB - BACKGROUND: Currently there is no drug proven to effectively treat cats with feline infectious peritonitis (FIP). HYPOTHESIS: Propentofylline (PPF) can decrease vasculitis, and therefore prolong survival time in cats with FIP, and increase their quality of life. ANIMALS: Twenty-three privately owned cats with FIP. METHODS: Placebo-controlled double-blind trial. FIP was confirmed by histology or immunostaining of feline coronavirus (FCoV) antigen in effusion or tissue macrophages or both. The cats were randomly selected for treatment with either PPF or placebo. All cats received additional treatment with glucocorticoids, antibiotics, and low molecular weight heparin according to methods. RESULTS: There was no statistically significant difference in the survival time of cats treated with PPF (8 days, 95% CI 5.4-10.6) versus placebo (7.5 days, 95% CI 4.4-9.6). The median survival time of all cats was 8 days (4-36 days). There was neither a difference in quality of life (day 7, P = .892), in the amount of effusion (day 7, P = .710), the tumor necrosis factor-alpha (TNF alpha) concentration (day 7, P = .355), nor in any other variable investigated in this study, including a complete blood count, and a small animal biochemistry profile. CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not detect an effect of PPF on the survival time, the quality of life, or any clinical or laboratory parameter in cats with FIP. Therefore, PPF does not appear to be an effective treatment option in cats with a late stage of the disease FIP. PMID- 22092617 TI - Severe myositis associated with Sarcocystis spp. infection in 2 dogs. AB - BACKGROUND: Dogs are definitive hosts for numerous species of the intracellular protozoan parasite Sarcocystis. Reports of sarcocysts in muscles of dogs most often represent incidental findings. HYPOTHESIS/OBJECTIVES: To report the clinicopathologic, ultrastructural, and molecular findings in 2 dogs with myositis associated with Sarcocystis spp. infection, as well as the response to treatment with antiprotozoal drugs. ANIMALS: Two dogs with severe myositis in association with massive sarcocystosis. METHODS: Retrospective case review. Affected dogs were identified by a diagnostic laboratory. Attending clinicians were contacted, and the medical records reviewed. Immunostaining and electron microscopy were performed on muscle biopsies. Biopsies also were subjected to 18S rRNA gene PCR. RESULTS: Both dogs had fever, lymphopenia, thrombocytopenia, and increased serum alanine aminotransferase (ALT) activity when first evaluated. One dog developed hyperbilirubinemia. Subsequently, both dogs had increased serum creatine kinase activity and clinical signs of myositis, with reluctance to move, generalized pain, and muscle wasting. Histopathology of muscle biopsies showed severe inflammatory and necrotizing myopathy with numerous sarcocysts. Ultrastructural studies and 18S rRNA gene sequence results were consistent with infection with a Sarcocystis spp. other than Sarcocystis neurona. Both dogs initially were treated unsuccessfully with clindamycin and anti-inflammatory drugs. One dog died. The other dog subsequently responded to treatment with decoquinate. CONCLUSIONS AND CLINICAL IMPORTANCE: Sarcocystis spp. infection should be included in the differential diagnosis for dogs that develop fever, thrombocytopenia, increased liver enzyme activities, and clinical and biochemical evidence of myositis. Although additional studies are required, decoquinate holds promise as an effective treatment for the disease. PMID- 22092618 TI - Molecular prevalence of Bartonella, Babesia, and hemotropic Mycoplasma sp. in dogs with splenic disease. AB - BACKGROUND: Among diseases that cause splenomegaly in dogs, lymphoid nodular hyperplasia (LNH), splenic hemangiosarcoma (HSA), and fibrohistiocytic nodules (FHN) are common diagnoses. The spleen plays an important role in the immunologic control or elimination of vector-transmitted, blood-borne pathogens, including Bartonella sp., Babesia sp., and hemotropic Mycoplasma sp. OBJECTIVE: To compare the prevalence of Bartonella sp., Babesia sp., and hemotropic Mycoplasma sp. DNA in spleens from dogs with LNH, HSA, and FHN. MATERIALS AND METHODS: Paraffin embedded, surgically obtained biopsy tissues from LNH (N = 50), HSA (N = 50), and FHN (N = 37) were collected from the anatomic pathology archives. Spleens from specific pathogen-free (SPF) dogs (N = 8) were used as controls. Bartonella sp., Babesia sp., and Mycoplasma sp. DNA was amplified by PCR, followed by DNA sequencing. RESULTS: Bartonella sp. DNA was more prevalent in FHN (29.7%) and HSA (26%) as compared to LNH (10%) (P = .019, .0373, respectively) or control spleens (0.0%). The prevalence of Babesia sp. and hemotropic Mycoplasma sp. DNA was significantly lower than Bartonella sp. DNA in HSA (P = .0005, .006, respectively) and FHN (P = .003, .0004, respectively). There was no statistically significant difference in DNA prevalence among the 3 genera in the LNH group. CONCLUSIONS: The higher prevalence of Bartonella sp. in FHN and HSA warrants future investigations to determine if this bacterium plays a role in the development of these splenic diseases. PMID- 22092619 TI - Quantitative and qualitative urine protein excretion in dogs with severe inflammatory response syndrome. AB - BACKGROUND: Proteinuria is an established characteristic of renal disease in dogs, providing diagnostic and prognostic information. Little is known about the occurrence and severity of proteinuria in dogs with severe inflammatory response syndrome (SIRS). HYPOTHESIS: The quantitative and qualitative urinary protein (UP) excretion is altered in dogs with SIRS. ANIMALS: Thirty-nine dogs with SIRS and 15 healthy control dogs at admission. METHODS: A case control study was performed. Diagnosis of SIRS was based on clinical and clinicopathological findings. Urinary protein (UP) was measured by a colorimetric assay. Urinary albumin (UAlb) and urinary retinol-binding protein (URBP) were measured by ELISA and quantified in relation to urinary creatinine (UC). Sodium dodecyl sulfate polyacrylamid-gel electrophoresis was conducted to identify the qualitative pattern of proteinuria. Mann-Whitney U-test was used to assess differences in UP/UC, UAlb/UC and URBP/UC between the groups. P-values < .05 were considered significant. RESULTS: Dogs with SIRS had higher ratios of UP/UC, UAlb/UC and URBP/UC (all P < .001) in comparison to healthy control dogs. Dogs with SIRS had a total of 11 protein bands compared to 3 bands in healthy controls. In dogs with SIRS, 58% of the total counted bands were in the low molecular weight range (<60 kDa) whereas 42% were in the middle (60-80 kDa)/high molecular weight range (>80 kDa). CONCLUSIONS AND CLINICAL IMPORTANCE: SIRS alters UP excretion in dogs. Further studies should evaluate whether or not the magnitude of proteinuria is predictive of the severity and outcome of dogs with SIRS. PMID- 22092620 TI - Dose reduction of meloxicam in dogs with osteoarthritis-associated pain and impaired mobility. AB - BACKGROUND: Progressive nonsteroidal anti-inflammatory drug (NSAID) dose reduction appears logical; however, there is no evidence-based medicine indicating that efficacy is maintained as dose is reduced. OBJECTIVE: To determine if NSAID dose can be reduced and pain relief and mobility can be maintained in dogs with osteoarthritis (OA). ANIMALS: Client-owned dogs (n = 59) with OA-associated impaired mobility and pain. METHODS: Prospective, randomized, blinded study. After 14 days wash-out, dogs were randomized to reducing dose (RDG) (n = 30) or maintenance dose (MDG) (n = 29). MDG received standard dose meloxicam. RDG received a reducing dose from D28 onward, reducing to 0% of maintenance for the final 2 weeks. Assessments were at D14, 28, 42, 56, 70, 84, 98 and 112 using subjective owner assessments, accelerometry (AM), and standing percent body weight distribution (%BW). A Kaplan-Meier survival curve described how dogs dropped out because of insufficient pain control. A Log-rank test compared the groups. RESULTS: More dogs in RDG (13) dropped out because of owner evaluated insufficient pain control compared with MDG (5) (P = .029; odds ratio: 3.67; median dropout time: 84 days in each group). For the dogs that did not drop out (n = 41), there were no significant differences between groups in owner assessments (P > .2 for each), %BW placed on the index limb (P = .750), or accelerometer-measured activity (P = .14). CONCLUSION AND CLINICAL RELEVANCE: Dose reduction is a less effective means of pain control compared with maintained dosing. However, NSAID dose reduction with maintained efficacy is possible, but success appears to be individual dog dependent. PMID- 22092621 TI - Association between body condition and survival in dogs with acquired chronic kidney disease. AB - BACKGROUND: Obesity in people with chronic kidney disease (CKD) is associated with longer survival. The purpose of this study was to determine if a relationship exists between body condition score (BCS) and survival in dogs with CKD. HYPOTHESIS/OBJECTIVES: Higher BCS is a predictor of prolonged survival in dogs with CKD. ANIMALS: One hundred dogs were diagnosed with CKD (International Renal Interest Society stages II, III or IV) between 2008 and 2009. METHODS: Retrospective case review. Data regarding initial body weight and BCS, clinicopathologic values and treatments were collected from medical records and compared with survival times. RESULTS: For dogs with BCS recorded (n = 72), 13 were underweight (BCS = 1-3; 18%), 49 were moderate (BCS = 4-6; 68%), and 10 were overweight (BCS = 7-9; 14%). For dogs with at least 2 body weights recorded (n = 77), 21 gained weight, 47 lost weight, and 9 had no change in weight. Dogs classified as underweight at the time of diagnosis (median survival = 25 days) had a significantly shorter survival time compared to that in both moderate (median survival = 190 days; P < .001) and overweight dogs (median survival = 365 days; P < .001). There was no significant difference in survival between moderate and overweight dogs (P = .95). CONCLUSIONS AND CLINICAL IMPORTANCE: Higher BCS at the time of diagnosis was significantly associated with improved survival. Further research on the effects of body composition could enhance the management of dogs with CKD. PMID- 22092622 TI - Radiographic heart size and its rate of increase as tests for onset of congestive heart failure in Cavalier King Charles Spaniels with mitral valve regurgitation. AB - BACKGROUND: In canine mitral regurgitation (MR) the rate of heart enlargement increases in the last year before congestive heart failure (CHF). Measurement of heart size and its rate of increase may be useful tests for CHF in MR. OBJECTIVES: To determine the value of vertebral heart scale (VHS) and its rate of increase (?VHS units/month) for diagnosing the presence and predicting the onset of CHF. ANIMALS: Longitudinal study of 94 Cavalier King Charles Spaniels (CKCS). METHODS: VHS was measured at intervals before CHF. ?VHS/month was calculated from sequential pairs of VHS measurements and the interval between them. Diagnostic accuracy and utility were determined by the areas under receiver operating characteristic plots (AUROC), and likelihood ratios (LR). RESULTS: AUROC for VHS at the onset of CHF was 0.93 (95% CI, 0.96-0.90), to predict CHF 1-12 months before CHF was 0.74 (95% CI, 0.81-0.66), and for ?VHS/month at CHF was 0.98 (95% CI, 0.99-0.96). Interval LRs and their cutoff values for CHF were for VHS: 13 (95% CI, 20-7.3) at >=12.7; 1.2 (95% CI, 2.0-0.68) between 12.7 and 12.0; 0.04 (95% CI, 0.18-0.01) at <=12.0, and for ?VHS/month: 15 (95% CI, 30-7.7) at >=0.08; 0.72 (95% CI, 2.0-0.25) between 0.08 and 0.06; and 0.05 (95% CI, 0.13-0.02) at <=0.06. CONCLUSIONS AND CLINICAL IMPORTANCE: Under the conditions of this study, VHS and particularly ?VHS/month are useful measurements for detecting onset of CHF in CKCS with MR. PMID- 22092623 TI - Comparisons of 2- and 3-dimensional echocardiographic methods for estimation of left atrial size in dogs with and without myxomatous mitral valve disease. AB - BACKGROUND: Two-dimensional (2D) and real-time three-dimensional (RT3D) echocardiography can be used to assess left atrial (LA) size, but their correlation in dogs remains unknown. HYPOTHESIS: Estimations of LA size differ depending on the echocardiographic technique. ANIMALS: Privately owned dogs; 70 with myxomatous mitral valve disease and 32 healthy control dogs. METHODS: Prospective observational study comparing RT3D volume at atrial end-diastole (RT3DLAd) with 4 different 2D methods of estimating LA size: LA diameter and area in short-axis (LA(sax) and LA(area)) and LA diameter in long-axis (LA(lax)), both as indexed variables and as predictors of LA volume indexed to body weight (BW) using allometric scaling and geometric assumption of sphericity. Furthermore, agreement between indexed 2D based methods was studied using concordance correlation coefficient (rho(c)) and Bland-Altman plots. RESULTS: None of the indexed 2D methods of estimating LA size showed good correlation with BW-indexed RT3DLAd volumes. Estimates of LA volumes from 2D measurements using allometric scaling showed better correlation with RT3D volumes than corresponding calculated volume approximations. The best correlation was found between RT3DLAd and estimated LA volumes based on allometric scaling of LA(lax) (rho(c) = 0.89) followed by LA(area) (rho(c) = 0.86) measurements. Comparing indexed 2D-based measurements of LA size, best agreement was found between LA(sax) to aortic diameter and LA(sax) to expected LA diameter, based on allometric scaling. CONCLUSIONS AND CLINICAL IMPORTANCE: Allometric scaling of 2D-based measurements of LA showed good correlation with RT3DLAd, whereas corresponding indexed measurements or calculated volume approximations did not. PMID- 22092624 TI - The effect of pimobendan on left atrial pressure in dogs with mitral valve regurgitation. AB - BACKGROUND: The effects of pimobendan on left atrial pressure (LAP) in dogs with mitral valve disease (MR) have not been documented in a quantitative manner. OBJECTIVE: The objective was to document and study the short-term effects of pimobendan on LAP and echocardiographic parameters in MR dogs. ANIMALS: Eight healthy Beagle dogs weighing 10.0-14.7 kg (3 males and 5 females; aged 2 years) were used. METHODS: Experimental, cross-over, and interventional study. Dogs with surgically induced MR received pimobendan at either 0.25 mg/kg or 0.50 mg/kg p.o. q12h for 7 days and then, after a 7-day wash-out period, the other dosage. LAP was measured for 30 minutes at baseline and again on days 1, 2, 4, and 7 of pimobendan administration. RESULTS: Mean LAP was significantly decreased after the administration of 0.25 mg/kg (15.81 +/- 5.44 mmHg to 12.67 +/- 5.71 mmHg, P < .001) and 0.50 mg/kg (15.76 +/- 5.45 mmHg to 10.77 +/- 5.23 mmHg, P < .001). Also, the 0.50 mg/kg group led to a significantly lower LAP (P < .01) compared with the 0.25 mg/kg group. Significant reduction was seen for the first time 4 days after the administration of 0.25 mg/kg and a day after the administration of 0.50 mg/kg. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan decreased LAP in a dose-dependent manner in dogs with acute MR caused by experimental chordal rupture. This study did not evaluate adverse effects of high-dose pimobendan, and additional studies in clinical patients are warranted. PMID- 22092625 TI - Randomized, blinded comparison of epinephrine and vasopressin for treatment of naturally occurring cardiopulmonary arrest in dogs. AB - BACKGROUND: Administration of epinephrine during CPR is recommended for treatment of cardiopulmonary arrest (CPA) in dogs. Administration of epinephrine during CPR might be associated with deleterious adverse effects. Vasopressin has been studied for use in CPR as an alternative. HYPOTHESIS: That administration of vasopressin instead of epinephrine with standard CPR techniques will result in improved outcome. ANIMALS: Seventy-seven client-owned dogs identified in the ER/ICU with CPA were eligible for inclusion. METHODS: Randomized, prospective clinical study. Dogs were randomized to receive epinephrine (0.01-0.02 mg/kg) or vasopressin (0.5-1 U/kg) in a blinded fashion. Attending veterinarians were asked to adhere to standardized CPR protocol for the 1st 6 minutes of CPR, during which time doses of the study drug were administered at 3-minute intervals. RESULTS: A total of 60 dogs completed this study with 31 receiving epinephrine and 29 receiving vasopressin. Overall rate of return of spontaneous circulation (ROSC) was 60% (36/60), 32% (19/60) of dogs survived to 20 minutes, 18% (11/60) survived to 1 hour. No difference was seen in rates of ROSC between the 2 groups (P = .20). Dogs receiving epinephrine were more likely to survive to 1 hour (odds ratio 5.86; 95% CI: 1.19-28.95) than those receiving vasopressin (P = .027). CONCLUSIONS AND CLINICAL IMPORTANCE: ROSC was similar in dogs receiving epinephrine or vasopressin. In this study, a survival advantage at 1 hour was seen in those animals receiving epinephrine. No advantage of routine use of vasopressin over epinephrine was detected. Further studies are required to examine subgroups of dogs that might benefit from specific interventions. PMID- 22092626 TI - Resting energy expenditure per lean body mass determined by indirect calorimetry and bioelectrical impedance analysis in cats. AB - BACKGROUND: Resting energy expenditure (REE) approximates >=60% of daily energy expenditure (DEE). Accurate REE determination could facilitate sequential comparisons among patients and diseases if normalized against lean body mass (LBM). OBJECTIVE: (1) Validate open-flow indirect calorimetry (IC) system and multifrequency bioelectrical impedance analysis (MF-BIA) to determine REE and LBM, respectively, in healthy nonsedated cats of varied body conditions; (2) normalize REE against LBM. ANIMALS: Fifty-seven adult neutered domestic short haired cats with stable BW. METHODS: Continuous (45-min) IC-measurements determined least observed metabolism REE. Cage gas flow regulated with mass flow controllers was verified using nitrogen dilution; span gases calibrated gas measurements. Respiratory quotient accuracy was verified using alcohol combustion. IC-REE was compared to DEE, determined using doubly labeled water. MF BIA LBM was validated against criterion references (deuterium, sodium bromide). Intra- and interassay variation was determined for IC and MF-BIA. RESULTS: Mean IC-REE (175 +/- 38.7 kcal; 1.5-14% intra- and interassay CV%) represented 61 +/- 14.3% of DEE. Best MF-BIA measurements were collected in sternal recumbency and with electrodes in neck-tail configuration. MF-BIA LBM was not significantly different from criterion references and generated LBM interassay CV% of 6.6 10.1%. Over- and underconditioned cats had significantly (P <= .05) lower and higher IC-REE (kcal/kg) respectively, compared with normal-conditioned cats. However, differences resolved with REE/LBM (approximating 53 +/- 10.3 kcal/LBM [kg]). CONCLUSIONS AND CLINICAL IMPORTANCE: IC and MF-BIA validated herein reasonably estimate REE and LBM in cats. REE/LBM(kg) may permit comparison of energy utilization in sequential studies or among different cats. PMID- 22092627 TI - White blood cell count and the sodium to potassium ratio to screen for hypoadrenocorticism in dogs. AB - BACKGROUND: Abnormal sodium to potassium (Na:K) ratios can raise suspicion for hypoadrenocorticism (HA). Although dogs with HA usually have normal leukograms, their white blood cell counts may be useful in screening for HA. OBJECTIVES: To examine the utility of combining the Na:K ratio with white blood cell counts to screen for HA in hospitalized dogs requiring fluid treatment administered i.v.. ANIMALS: Fifty-three dogs with confirmed HA and 110 sick dogs confirmed not to have HA. METHODS: Retrospective, case-control study. Dogs were included if they were hospitalized and administered fluids i.v., had a complete blood count and measurement of serum Na and K concentrations. HA was diagnosed using an ACTH stimulation test, or ruled out by measurement of basal serum cortisol concentration. RESULTS: The receiver operating characteristic (ROC) curve for the lymphocyte count was not significantly different from the ROC curve of the Na:K ratio (P = .55). The ROC curve for the model combining the Na:K ratio and lymphocyte count was superior for identifying dogs with HA compared to the Na:K ratio (P = .02) or lymphocyte count (P = .005) alone. At the 100% sensitivity cutoff, lymphocyte count was more specific for detection of HA than Na:K (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of the Na:K ratio and lymphocyte count provides a better screening test for HA compared to the Na:K ratio or lymphocyte count alone. At 100% sensitivity, the lymphocyte count is a more specific test for HA than the Na:K. PMID- 22092628 TI - The efficacy and safety of a novel lipophilic formulation of methimazole for the once daily transdermal treatment of cats with hyperthyroidism. AB - BACKGROUND: Previous studies on transdermal methimazole have used pluronic lecithin organogel as the vehicle. This might not be the most suitable vehicle for a lipophilic drug, such as methimazole. HYPOTHESIS/OBJECTIVES: Once daily transdermal administration of a novel lipophilic formulation of methimazole is as safe and effective as oral carbimazole in treating hyperthyroidism in cats. ANIMALS: Forty-five client-owned cats diagnosed with hyperthyroidism. METHODS: Prospective study. Cats with newly diagnosed, untreated hyperthyroidism were treated with carbimazole (5 mg p.o., q12h) or methimazole (10 mg) applied to the inner pinnae q24h. Cats were examined after 0, 1, 4, 8, and 12 weeks of treatment. Clinical signs, body weight, systolic blood pressure, hematologic, serum biochemical and urine parameters, total serum thyroxine concentrations (TT4), and serum methimazole concentrations were recorded. RESULTS: No significant differences between groups were detected at day 0. Both formulations were effective in treating hyperthyroidism. No significant differences were detected in thyroxine concentrations, body weight, blood pressure, heart rate, alkaline phosphatase, alanine aminotransferase, creatinine, urea, and urine specific gravity (USG) between groups. The serum methimazole concentrations correlated poorly with TT4-concentrations in both groups. CONCLUSIONS AND CLINICAL IMPORTANCE: In this 12-week trial, once daily application of a novel formulation of transdermal methimazole applied to the pinnae was as effective and safe as twice daily oral carbimazole in the treatment of cats with hyperthyroidism. This novel formulation and transdermal application could have practical advantages to some pet owners. PMID- 22092629 TI - Transient evoked otoacoustic emissions testing for screening of sensorineural deafness in puppies. AB - BACKGROUND: Transient evoked otoacoustic emissions (TEOAE) are widely used for human neonatal deafness screening, but have not been reported for clinical use in dogs. HYPOTHESIS/OBJECTIVES: To investigate the feasibility of TEOAE testing in conscious puppies and the ability of TEOAE testing to correctly identify deaf and hearing ears, as defined by brainstem auditory evoked response (BAER). ANIMALS: Forty puppies from 10 litters. METHODS: Prospective study on puppies presented for hearing assessment as part of a congenital deafness BAER screening program. Hearing status was determined using BAER. TEOAE testing was performed after the BAER assessment and the results of the TEOAE testing were compared with the hearing status for each ear. Parameters were tested for normality using the D'Agostino Pearson test and comparisons between the deaf and hearing ears were made using Mann-Whitney tests. RESULTS: TEOAE testing was readily performed in puppies presented for congenital deafness screening. Using analysis parameters based on those used in human neonatal hearing screening, TEOAE testing correctly identified all deaf ears, as defined by BAER testing, with a sensitivity of 100% (95% CI: 56-100%) for diagnosing deafness and specificity of 78% (95% CI: 66 87%). CONCLUSIONS AND CLINICAL IMPORTANCE: TEOAE testing is an effective screening modality for identifying congenital sensorineural deafness in dogs. In light of the simpler and less expensive equipment, TEOAE testing has the potential to improve access to hearing screening and through this reduce the prevalence of congenital deafness in the dog. PMID- 22092630 TI - Epilepsy in the Petit Basset Griffon Vendeen: prevalence, semiology, and clinical phenotype. AB - BACKGROUND: Epilepsy with a genetic background is increasingly being identified. In certain dog breeds, epilepsy occurs with a higher prevalence than the estimate of 1-2% reported in the general dog population. HYPOTHESIS: The Petit Basset Griffon Vendeen (PBGV) experiences an increased occurrence of epilepsy compared to the general dog population. ANIMALS: The target population consisted of all 876 PBGV dogs registered in the Danish Kennel Club from January 1, 1999 to December 31, 2008. The study population included 820 dogs that met the inclusion criteria. METHODS: A population study was conducted to estimate the prevalence of epilepsy in the Danish PBGV population. A mailed questionnaire was used to detect possible signs of epilepsy. The information was subsequently validated by telephone interviews of positive and possible positive responders and a negative responder control group, using an extensive questionnaire developed to detect epilepsy. Dogs evaluated as epilepsy positive after the telephone interview were offered a clinical investigation. RESULTS: The prevalence of epilepsy was estimated to be 8.9% (42/471) in the PBGV population. Average age of onset was 26.3 months. Sex and mode of response did not affect the prevalence, but a strong litter effect was seen. Among euthanized dogs, epilepsy was the predominant cause (6/45 = 13.3%). CONCLUSION AND CLINICAL IMPORTANCE: Petit Basset Griffon Vendeen dogs experience an increased risk of epilepsy characterized by a relatively early onset and dominated by focal seizures with and without secondary generalization. With an estimated prevalence of 8.9% and substantial clustering within litters, a genetic factor associated with epilepsy is suspected. PMID- 22092631 TI - Incidence of postoperative seizures with and without levetiracetam pretreatment in dogs undergoing portosystemic shunt attenuation. AB - BACKGROUND: In dogs with congenital portosystemic shunts (CPS), postligation seizures can be challenging to treat and often result in mortality. Levetiracetam (LEV) is a novel anticonvulsive drug that is commonly used in humans with seizure disorders who have hepatic comorbidity. OBJECTIVES: To compare the incidence of postoperative seizures in dogs that underwent surgical attenuation of an extrahepatic CPS and preoperatively received either LEV or no anticonvulsant medication. ANIMALS: A total of 126 dogs undergoing attenuation of an extrahepatic CPS that preoperatively received either LEV or no anticonvulsant medication. METHODS: Retrospective case review. Information obtained included signalment, duration of clinical signs, presence of neurologic abnormalities before surgery, preoperative bile acid and ammonia concentrations, diagnostic imaging modality, duration of hospitalization, postoperative complications including seizures, and discharge status. Bayesian Poisson regression was used to estimate the risk of seizures in LEV-treated dogs when compared with untreated dogs. RESULTS: Levetiracetam was administered to 33% (42/126) of dogs. No dog treated with LEV experienced postoperative seizures, whereas 5% (4/84) of dogs not treated with LEV experienced postoperative seizures. The relative risk of seizures was significantly (P < .0002) < 1 for the LEV-treated dogs, indicating LEV protection against development of postoperative seizures. No dog that experienced postoperative seizures survived to discharge from the hospital. CONCLUSIONS AND CLINICAL IMPORTANCE: Levetiracetam administered at 20 mg/kg p.o. q8h for a minimum of 24 hours before surgery significantly decreased the risk of postoperative seizures and death in dogs undergoing surgical attenuation of extrahepatic CPS with ameroid ring constrictors. PMID- 22092632 TI - Clinical trial of vinblastine in dogs with transitional cell carcinoma of the urinary bladder. AB - BACKGROUND: Transitional cell carcinoma (TCC) of the urinary bladder of dogs can be a difficult cancer to treat, and effective therapies are limited. Vinblastine has been used in humans with TCC and has potent anti-proliferative effects against canine TCC cells in vitro. OBJECTIVES: To determine the antitumor activity and toxicoses of vinblastine in dogs with urinary bladder TCC. ANIMALS: Animals selected were 28 privately owned dogs that presented to the Purdue University Veterinary Teaching Hospital (PUVTH) with measurable, histologically confirmed TCC. METHODS: Prospective clinical trial: The starting vinblastine dosage was 3.0 mg/m(2) i.v. every 2 weeks. Treatment continued until cancer progression or unacceptable toxicoses occurred. Complete evaluations (physical exam, complete blood count [CBC], serum biochemical profile, urinalysis, thoracic radiography, abdominal ultrasound [US]) were performed at 8-week intervals. Urinary tract US with bladder tumor mapping was performed monthly. Toxicoses were graded according to Veterinary Co-Operative Oncology Group (VCOG) criteria. RESULTS: Tumor responses included 10 (36%) partial remission, 14 (50%) stable disease, and 4 (14%) progressive disease. The median progression free interval was 122 days (range, 28-399 days). The median survival time was 147 days (range, 28-476 days) from 1st vinblastine treatment to death and 299 days (range, 43-921 days) from diagnosis to death. The majority of dogs (27 of 28) did not have clinically relevant adverse effects. Seventeen of 28 (61%) dogs required dosage reductions because of neutropenia. CONCLUSION AND CLINICAL IMPORTANCE: Vinblastine has antitumor activity against TCC in dogs and can be considered another treatment option for this cancer. PMID- 22092633 TI - Pharmacodynamic monitoring of canine T-cell cytokine responses to oral cyclosporine. AB - BACKGROUND: Pharmacodynamic assays measure the immunosuppressive effects of cyclosporine on T-cells and offer an alternative assessment of efficacy in individual patients. OBJECTIVE: To assess the immunosuppressive effects of high and low dosage cyclosporine on canine T-cells and to develop a novel testing system for individualized dose adjustment. ANIMALS: Seven healthy female Walker hounds. METHODS: Experimental study using a paired comparison design. Flow cytometry was used to measure T-cell expression of IL-2, IL-4, and IFN-gamma. Cytokine expression 8 days after oral administration of high and low dosages of cyclosporine was compared to baseline and washout values, respectively. The high dosage was initially 10 mg/kg q12h and was then adjusted to attain established immunosuppressive trough blood drug concentrations (>600 ng/mL). The low dosage was 5 mg/kg q24h. RESULTS: High dosage cyclosporine resulted in significant decreases in IL-2 and IFN-gamma expression (P = .0156, P = .0156), but not IL-4 expression (P = .2188). Low dosage cyclosporine was associated with a significant decrease in IFN-gamma expression (P = .0156), while IL-2 expression was not affected (P = .1094). CONCLUSIONS AND CLINICAL IMPORTANCE: T-cell function is suppressed at trough blood drug concentrations exceeding 600 ng/mL, and is at least partially suppressed in some dogs at low dosages. Direct evaluation of T cell function could be an effective, more sensitive alternative to measuring blood drug concentrations for monitoring immunosuppressive therapy. PMID- 22092634 TI - Canine cutaneous perivascular wall tumors at first presentation: clinical behavior and prognostic factors in 55 cases. AB - BACKGROUND: Canine cutaneous perivascular wall tumors (c-PWT) are soft tissue sarcomas recently identified when hemangiopericytomas were reclassified. No previous clinical data are available for c-PWT. HYPOTHESIS/OBJECTIVES: To define the clinical behavior and prognostic role of clinical and pathological variables in a homogeneous population of c-PWT. ANIMALS: Fifty-five c-PWT in 53 client owned dogs at first presentation undergoing surgery. METHODS: Retrospective case series. The endpoint was the relapse of tumor (local and/or distant). The prognostic values of clinical (age, sex, weight, site and tumor size, adjuvant therapy) and pathological (status of surgical margins, histological grade, mitosis, percentage of tumor necrosis) variables were investigated by univariate and bivariate analyses (P < .05). The pattern of associations between variables was explored by multivariate correspondence analysis (MCA). RESULTS: Twelve dogs had a relapse. Ten dogs had local recurrence, 1 had metastatic disease, and 1 had both. The estimated probability of local recurrence was 0.02, 0.08, 0.20, and 0.24 at 6 months, 1, 2, and 3 years, respectively. Size of the tumor was a significant prognostic factor while status of margins had only a clinically relevant hazard ratio. In MCA evaluation, young age, tumor size (< 5 cm), grade I, and location in the extremities were associated. Association was also observed for older age, tumor size (> 5 cm), grade II, and other location. CONCLUSION AND CLINICAL IMPORTANCE: C-PWT tend to locally recur a long time after surgery. An early diagnosis of c-PWT associated with small tumor size (< 5 cm) and clean surgical margins ensures a good prognosis independently of histological grade. PMID- 22092635 TI - Collection of peripheral blood CD34+ progenitor cells from healthy dogs and dogs diagnosed with lymphoproliferative diseases using a Baxter-Fenwal CS-3000 Plus blood cell separator. AB - BACKGROUND: Canine peripheral blood mononuclear cell (PBMC) apheresis using a Baxter-Fenwal CS-3000 Plus automated blood cell separator has not been reported. OBJECTIVE: To determine the feasibility and safety of using a CS-3000 Plus blood cell separator with a small volume separation container holder (SVSCH) and small volume collection chamber (SVCC) to harvest canine PBMCs from dogs weighing <50 kg. ANIMALS: Eight healthy mongrel dogs and 11 client-owned dogs in clinical remission for lymphoproliferative diseases (LPD). METHODS: In this prospective study, aphereses were performed using a Baxter-Fenwal CS-3000 Plus blood cell separator, with or without recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment. RESULTS: Aphereses from 6 healthy dogs given rhG-CSF yielded an average of 1.1 * 10(7) +/- 8.2 * 10(6) CD34+ cells/kg. Aphereses from LPD dogs given rhG-CSF yielded an average of 5.4 * 10(6) +/- 3.25 * 10(6) CD34+ cells/kg (P = .17). Higher hematocrit in both groups of dogs receiving rhG-CSF correlated with an increased number of CD34+ cells/kg harvested (healthy, P = .04; LPD, P = .05). Apheresis was well tolerated by all dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine PBMC apheresis using the Baxter-Fenwal CS-3000 Plus cell separator with an SVSCH and SVCC is a feasible and safe option for harvesting an adequate number of CD34+ peripheral blood progenitor cells from dogs weighing >=17 kg for hematopoietic cell transplantation. PMID- 22092636 TI - Serial measurement of lactate concentration in horses with acute colitis. AB - BACKGROUND: Serial measurement of lactate concentration is utilized for therapeutic and prognostic purposes in human critical care. The prognostic value of serial lactate measurement in equine acute colitis warrants investigation. HYPOTHESIS: Serial lactate concentrations are predictive of outcome in horses with colitis. ANIMALS: A total of 101 horses with colitis. METHODS: Retrospective study. Plasma L-lactate concentrations were measured at admission and at 4-8 and 24 hours after admission. Associations between admission, early (4-8 hours) and late (24 hours) lactate concentrations, and survival status were determined. The percent reduction in lactate concentration between admission and the early time point, and between admission and the late time point, was calculated. Using a cutoff value, associations between percent reduction in lactate and survival status and associations between percent reduction in lactate and clinical and clinicopathologic data were determined. RESULTS: There was no association between admission plasma lactate concentration and survival status (P = .26). The 4-8 and 24 hour after admission lactate concentrations were associated with survival status (P = .023, .013, respectively). Lactate cutoffs of <=2.3 and <=1.5 mmol/L had the maximum sensitivity and specificity for predicting survival at the 4-8 and 24 hour time points, respectively. When lactate reduction >=30% at 4-8 hours and >=50% at 24 hours after admission were used as the cutoffs, the percent reduction of lactate concentration was significantly associated with survival (P = .012 and .019, respectively). CONCLUSION AND CLINICAL IMPORTANCE: The prognostic ability of serial measurement of blood lactate concentration warrants prospective study as a measure of therapeutic response in horses with colitis. PMID- 22092637 TI - Hyperlipemia in a population of aged donkeys: description, prevalence, and potential risk factors. AB - BACKGROUND: Hyperlipemia is a common disorder of the donkey, with mortality rates of up to 80% reported. Such a poor prognosis makes prevention of this disorder or amelioration in the early stages crucial. OBJECTIVES: The objective of this study was to describe and determine the prevalence of hyperlipemia in a population of donkeys and to determine risk factors for development of the disease. ANIMALS: A total of 449 cases were investigated from a population of 3829 donkeys; donkeys were resident at The Donkey Sanctuary, a charity providing refuge for unwanted donkeys in the UK. Animals were selected on the basis of presence of clinical disease. METHODS: A retrospective case-control study design was used, and all donkeys presenting with hyperlipemia over a 4-year period were included. Each case was matched with 2 controls that had not suffered from hyperlipemia in the previous month. Multivariable analysis was carried out to determine risk factors. RESULTS: A total of 449 clinical cases of hyperlipemia were reported with an associated mortality rate of 48.5%. Concurrent disease was present in 72% of donkeys and was the greatest risk factor (OR = 76.98); others included cardboard bedding (OR = 3.86), movement (OR = 3.94), weight loss (OR = 6.4), dental disease (OR = 1.73), and concentrate feeding (OR = 1.87). CONCLUSIONS: This study shows that this population of donkeys in the UK often develops hyperlipemia, particularly in response to stress or primary illness, and provides useful insights in to health and management risk factors that may be addressed to decrease the risk of hyperlipemia both in the study population and in other similar donkey populations. PMID- 22092638 TI - The relationship between serum calcium concentration and outcome in horses with renal failure presented to referral hospitals. AB - BACKGROUND: Hypercalcemia is common in horses with renal failure, but it is not known whether it impacts prognosis. HYPOTHESIS/OBJECTIVES: The primary objective of this study was to determine whether hypercalcemia was associated with decreased likelihood of survival to discharge in horses with renal failure. Secondary objectives were to determine whether hypercalcemia was more common in acute (ARF) or chronic renal failure (CRF), whether feeding alfalfa was associated with hypercalcemia, and whether serum creatinine concentration was associated with survival. ANIMALS: Medical records of 63 horses presented to referral hospitals for renal failure were evaluated. Cases were classified as ARF or CRF based on historical and clinical findings. METHODS: The distribution of hypocalcemic, normocalcemic, and hypercalcemic cases in the ARF and CRF groups was determined. Mean serum calcium and creatinine concentrations for survivors and nonsurvivors, and for ARF and CRF cases, were compared. Mean serum calcium concentrations for cases fed alfalfa or not fed alfalfa were compared. RESULTS: Hypercalcemia was significantly more common in CRF than ARF cases. CRF cases fed alfalfa were significantly more likely to be hypercalcemic. There was no significant difference in serum calcium concentration between survivors and nonsurvivors. Serum creatinine concentration was significantly higher in nonsurvivors and in ARF cases. CONCLUSIONS AND CLINICAL IMPORTANCE: Horses with CRF are more likely to be hypercalcemic than horses with ARF. Hypercalcemia was not associated with outcome in renal failure cases in this study. Additional research on the impact of dietary calcium on long-term well-being in horses with CRF is warranted. PMID- 22092639 TI - Comparison of cortisol and ACTH responses after administration of thyrotropin releasing hormone in normal horses and those with pituitary pars intermedia dysfunction. AB - BACKGROUND: Changes in both adrenocorticotropin (ACTH) and cortisol concentration in response to thyrotropin releasing hormone (TRH) administration have been used to diagnose equine pituitary pars intermedia dysfunction (PPID), but the use of the 2 hormones has not been compared. HYPOTHESES: Measuring ACTH concentration is superior to measuring cortisol concentration after TRH administration in differentiating between normal horses and those with PPID, and the 2 hormone concentrations are disassociated in PPID horses. ANIMALS: Eleven horses and 2 ponies with PPID and 19 normal horses. METHODS: A study evaluating cortisol and ACTH concentrations before and at 14, 30, and 60 minutes after TRH administration. RESULTS: At 14 and 30 minutes after TRH administration, cortisol concentration increased in PPID horses, and ACTH increased in all groups; ACTH, but not cortisol concentration, was significantly higher in PPID horses compared with normal horses. A relationship between cortisol concentration and ACTH concentration was seen in normal horses, but not in horses with PPID. Compared with normal castrated males, normal female horses had a greater change in cortisol concentration per unit change of ACTH concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: ACTH and cortisol concentrations are disassociated in horses with PPID. Measuring ACTH concentration after TRH administration appears superior to measuring cortisol concentration as a diagnostic test for PPID. PMID- 22092640 TI - Equine degenerative myeloencephalopathy in Lusitano horses. AB - BACKGROUND: Equine degenerative myeloencephalopathy (EDM) is a neurodegenerative disorder that has been previously associated with low vitamin E concentrations. OBJECTIVE: To describe the clinical, electrophysiologic, and pathologic features of EDM in a group of related Lusitano horses. ANIMALS: Fifteen Lusitano horses. PROCEDURES: Neurologic examinations were conducted, and serum vitamin E concentrations were measured. Three neurologically abnormal horses were further evaluated by ophthalmologic examination, electroretinography, electroencephalography, muscle and nerve biopsies, and post-mortem examination. RESULTS: Six horses appeared neurologically normal, 6 were neurologically abnormal, and 3 had equivocal gait abnormalities. Abnormal horses demonstrated ataxia and paresis. An inconsistent menace response was noted in 4 neurologically abnormal horses and in 1 horse with equivocal findings. All horses had low serum vitamin E concentrations (<1.5 ppm). Ophthalmologic examinations, electroretinograms, electroencephalograms, and muscle and peripheral nerve biopsies were unremarkable in 3 neurologically abnormal horses. At necropsy, major neuropathological findings in these horses were bilaterally symmetric, severe, neuro axonal degeneration in the gracilis, cuneatus medialis, cuneatus lateralis, and thoracicus nuclei and bilaterally symmetric axonal loss and demyelination mainly in the dorsolateral and ventromedial tracts of the spinal cord. A diagnosis of EDM was made based on these findings. Pedigree analysis identified 2 sires among the affected horses. CONCLUSIONS AND CLINICAL RELEVANCE: Equine degenerative myeloencephalopathy is a neurodegenerative disorder that causes ataxia and, in severe cases, paresis, in young Lusitano horses. The disease appears to have a genetic basis, and although vitamin E deficiency is a common finding, low serum vitamin E concentrations also may occur in apparently unaffected related individuals. PMID- 22092641 TI - A randomized clinical trial evaluating a farm-of-origin autogenous Moraxella bovis vaccine to control infectious bovine keratoconjunctivis (pinkeye) in beef cattle. AB - BACKGROUND: A randomized, masked, 2-arm parallel trial was conducted to assess the efficacy of a Moraxella bovis (M. bovis) autogenous vaccine to prevent naturally occurring infectious bovine keratoconjunctivis (IBK) in beef calves. HYPOTHESIS: The null hypothesis was that treatment group was not associated with either risk of IBK or last observed weight. ANIMALS: The trial was conducted between May and November 2009 and 2010 on a university-owned farm in Iowa. The vaccine contained 2 randomly selected M. bovis from IBK cases that occurred at the farm in 2008. Calves born between January and May 2009 and 2010 without visible corneal lesions were randomly allocated to receive vaccine (n = 191) or placebo (n = 178). METHODS: Two s.c. doses were administered 21-28 days apart. Allocation to treatment was concealed using bottles marked A or B. Staff observing the animals for IBK could not determine the treatment grouping. The herd met the "at-risk" criteria (ie, >15% IBK in unvaccinated calves and M. bovis detection in IBK cases). Analysis was "per-protocol". RESULTS: The risk of IBK was 58/185 (31%) in vaccinated calves and 66/173 (38%) in unvaccinated calves (adjusted risk ratio = 0.78; 95% CI, 0.49-1.24). Average weight before sale did not differ between the vaccinated calves (196.6 kg, SD +/- 39.9) and unvaccinated calves (198.1 kg, SD +/- 42.7) (P value = .19). No adverse effects were noted. CONCLUSION AND CLINICAL IMPORTANCE: Combination of the study results with previous studies suggests that autogenous M. bovis vaccines often are ineffective in controlling naturally occurring IBK. PMID- 22092642 TI - Renal tubular acidosis associated with zonisamide therapy in a dog. PMID- 22092643 TI - Dynamic collapse of the common pharynx in a cat. PMID- 22092644 TI - Ultrasonographic evaluation of vincristine-induced gastric hypomotility and the prokinetic effect of mosapride in dogs. AB - BACKGROUND: Vincristine induces gastrointestinal motility disorders in humans. Adverse gastrointestinal events are commonly observed in dogs receiving vincristine. OBJECTIVES: To evaluate gastric motility after vincristine administration in dogs and the prophylactic effect of a prokinetic agent, mosapride. ANIMALS: Five healthy Beagle dogs. METHODS: Five dogs received vincristine i.v. at a dosage of 0.75 mg/m(2). The motility index (MI) of the antral contraction was ultrasonographically evaluated 30 minutes postfeeding before administration of vincristine and for 6 days after vincristine treatment. After a 6-week washout period, the dogs received vincristine with mosapride (2 mg/kg p.o., q24h for 6 days), and the MI was re-evaluated. Adverse gastrointestinal events were evaluated according to the Veterinary Co-operative Group Common Terminology Criteria for Adverse Events (VCOG-CTCAE). RESULTS: After vincristine administration, a significant decrease (P < .05) in MI was observed on days 3 (6.64 +/- 0.30) and 4 (8.02 +/- 0.94), compared with pretreatment levels (10.00 +/- 0.62). Gastrointestinal adverse events were observed in 4 dogs (grade 2 decreased appetite: 3 dogs; grade 1 vomiting: 2 dogs; and grade 1 diarrhea and grade 2 hematochezia: 1 dog). When mosapride citrate was administered with vincristine and for the next 5 days, no decrease in MI was observed. Furthermore, adverse gastrointestinal events occurred less frequently (grade 1 vomiting and grade 2 hematochezia in 1 dog each). CONCLUSIONS AND CLINICAL IMPORTANCE: Vincristine (0.75 mg/m(2)) induces gastric hypomotility in dogs. Preventive administration of mosapride citrate (2.0 mg/kg p.o., q24h) improves hypomotility and may decrease the adverse gastrointestinal effects of vincristine. PMID- 22092645 TI - Comparison of four refractometers for the investigation of the passive transfer in beef calves. AB - BACKGROUND: Failure of passive transfer (FPT) in beef calves can be detected by refractometry. Nevertheless, different models of refractometers are available, and few studies compare them for the detection of FPT. OBJECTIVES: To compare the accuracy of 4 different refractometers for measuring serum total protein concentrations in comparison with results obtained by the biuret method and, based on the serum IgG threshold of 1,600 mg/mL, to determine, for each refractometer, the optimal serum protein concentration's lowest threshold for successful passive transfer. ANIMALS: One hundred and eight healthy beef calves, 3-8 days of age. METHODS: Observational study. The concentrations of serum total proteins were determined with 4 different models of refractometers and compared with the biuret method by a Bland-Altman statistical method. The optimal serum protein concentration's lowest threshold for successful passive transfer was determined for each refractometer by receiver operating characteristic (ROC) analysis. In addition, the serum immunoglobulin G (IgG) concentration was compared with the serum gamma-glutamyl transferase (gamma-GT) activity and with the total immunoglobulin concentration. RESULTS: The refractometric measurements were highly correlated with those obtained by the biuret method. Serum total protein concentration threshold values of 56, 58, 54, and 56 g/L were found respectively for the Atago, Atago ATC, Wolf ATC, and digital ATC refractometers. Immunoglobulins were highly correlated with IgG, whereas gamma-GT only reflected colostrum uptake by the calf. CONCLUSIONS AND CLINICAL IMPORTANCE: All refractometers could be used for the assessment of passive transfer using their individual serum protein concentration threshold. PMID- 22092647 TI - Pre-operative measurement of the volume of bone graft in sinus lifts using CompuDent. AB - OBJECTIVE: The aim of this study was to calculate the volume of graft necessary for rehabilitation using varying lengths of implants, and to evaluate the usefulness of the planning dental software in determining the pre-operative volume of bone graft in maxillary sinus floor lifts. MATERIAL AND METHODS: Using the CompuDent program, we calculated the volume of graft necessary for 62 sinus lifts. This volume was measured to raise the floor of each sinus to 13.4 and 15 mm in height. RESULTS: The average volume of graft to achieve a lift of 13.4 mm was 2.61 +/- 0.69 cm3 for the right maxillary sinus, with the range of 1.38-4.1 cm3, and 2.68 +/- 0.81 cm3 for the left maxillary sinus, with the range of 1.1 4.25 cm3. The average volume of graft to achieve a lift of 15 mm was 3.13 +/- 0.75 cm3 for the right maxillary sinus, with the range of 1.59-4.81 cm3, and 3.29 +/- 1.02 cm3 for the left maxillary sinus, with the range of 1.48-5.11 cm3. The statistical results showed a significant inversely proportional correlation between the average of the heights and the volume of graft in the right sinus. CONCLUSIONS: The planning dental software is an effective tool in determining the volume of bone graft given the tool's simplicity, rapidness and possibility of standardization in all pre-surgical procedures. PMID- 22092648 TI - Strength, diversity and plasticity of postmating reproductive barriers between two hybridizing oak species (Quercus robur L. and Quercus petraea (Matt) Liebl.). AB - Very little is known about the nature and strength of reproductive isolation (RI) in Quercus species, despite extensive research on the estimation and evolutionary significance of hybridization rates. We characterized postmating pre- and postzygotic RI between two hybridizing oak species, Quercus robur and Quercus petraea, using a large set of controlled crosses between different genotypes. Various traits potentially associated with reproductive barriers were quantified at several life history stages, from pollen-pistil interactions to seed set and progeny fitness-related traits. Results indicate strong intrinsic postmating prezygotic barriers, with significant barriers also at the postzygotic level, but relatively weaker extrinsic barriers on early hybrid fitness measures assessed in controlled conditions. Using general linear modelling of common garden data with clonal replicates, we showed that most traits exhibited important genotypic differences, as well as different levels of sensitivity to micro-environmental heterogeneity. These new findings suggest a large potential genetic diversity and plasticity of reproductive barriers and are confronted with hybridization evidence in these oak species. PMID- 22092649 TI - Bovine immune-mediated hemolytic anemia: 13 cases (November 2008-August 2009). AB - BACKGROUND: Immune-mediated hemolytic anemia (IMHA) occurs in cattle; however, there are few reported cases. OBJECTIVE: The aim of this study was to investigate the prevalence of IMHA in cattle with anemia, describe the associated clinical and laboratory findings, including osmotic fragility, and identify potential causative infectious agents or drugs. METHODS: This study included 42 anemic cattle (HCT < 27.5%) comprising 31 females and 11 bulls with a mean age of 3.5 years referred to the University of Tehran Veterinary Teaching Hospital during a 10-month period. CBCs, saline osmotic fragility tests, direct Coombs' tests, and biochemical profiles were performed, and blood smears were evaluated for spherocytosis, parasites, and microscopic agglutination. Five clinically healthy cattle were used as controls for testing osmotic fragility of RBCs. RESULTS: The Coombs' test was positive in 13/42 (30%) cattle; 5 had no evidence of concurrent disease or history of drug administration, and 8 had underlying or concurrent diseases, positivity for BLV, or exposure to drugs. The HCT (mean +/- SE) of Coombs'-positive cattle (16 +/- 1.7%) was significantly lower than that of Coombs'-negative animals (21 +/- 0.8%). Hematologic and biochemical findings in cattle with IMHA included anisocytosis (2), polychromasia (2), basophilic stippling (2), spherocytosis (2), hyperfibrinogenemia (5), left-shifted neutrophilia (3), and hyperbilirubinemia (8). RBCs from Coombs'-positive anemic cattle were more fragile than those from Coombs'-negative anemic cattle. Four osmotically different populations of RBCs were detected in cattle with IMHA, whereas RBC populations were homogeneous in the Coombs'-negative anemic cattle and in normal cattle. CONCLUSION: IMHA was identified in a significant proportion of anemic cattle. Idiopathic IMHA and IMHA secondary to infectious diseases and administration of certain drugs occur in cattle. PMID- 22092650 TI - An investigation of coagulation cascade activation and induction of fibrinolysis using foam sclerotherapy of reticular veins. AB - BACKGROUND: Coagulation parameters have not been investigated when foam sclerotherapy is used to treat reticular leg veins. OBJECTIVE: To evaluate the effect of foam bubbles on coagulation and fibrinolysis by measuring platelet count and concentrations of clotting factors and fibrinogen after foam sclerotherapy with sodium tetradecyl sulfate (STS) mixed with room air. MATERIALS AND METHODS: Patients with reticular veins received treatment with up to 30 mL of foam sclerotherapy prepared with STS and room air in a 1:4 ratio (1 mL STS, 4 mL room air) using the double-syringe technique. Venous blood was drawn immediately beforesclerotherapy and 15 minutes after the procedure. Pre- and post-treatment laboratory values were compared. RESULTS: Subjects treated with up to 30 mL of foam (30 mL foam = 6 mL sclerosing solution and 24 mL air) showed no statistically significant difference in coagulation or fibrinolysis, as measured according to platelet count and concentrations of clotting factors and fibrinogen, after foam sclerotherapy with STS mixed with room air. CONCLUSION: STS foam made with room air, up to 30 mL, when injected into reticular veins does not affect coagulation parameters. PMID- 22092651 TI - Semaphorin 3C is not required for the establishment and target specificity of the GABAergic septohippocampal pathway in vitro. AB - The septohippocampal (SH) pathway comprises cholinergic and GABAergic fibers. Whereas the former establish synaptic contacts with all types of hippocampal neurons, the latter form complex baskets specifically on interneurons. The GABAergic SH function is associated with the control of hippocampal synchronous networks. Little is known about the mechanisms involved in the formation of the GABAergic SH pathway. Semaphorin (Sema) 3C is expressed in most hippocampal interneurons targeted by these axons. To ascertain whether Sema 3C influences the formation of the SH pathway, we analyzed the development of this connection in Sema 3C-deficient mice. As these animals die at birth, we developed an in vitro organotypic co-culture model reproducing the postnatal development of the SH pathway. In these SH co-cultures, the GABAergic SH pathway developed with target specificity similar to that present in vivo. SH axons formed incipient baskets on several types of hippocampal interneurons at 7 days in vitro, which increased their complexity by 18-25 days in vitro. These SH fibers formed symmetric synaptic contacts on GABAergic interneurons. This synaptic specificity was not influenced by the absence of entorhinal afferents. Finally, the absence of Sema 3C in target neurons or its blockage by neuropilin-1 and -2 ectodomains in slice co-cultures did not lead to major changes in either the target specificity of the GABAergic SH pathway or its density of innervation. We conclude that the formation and synaptic specificity of the GABAergic SH pathway relies on robust molecular mechanisms, independent of Sema 3C, that are retained in our in vitro co-culture model. PMID- 22092652 TI - Conjunctival provocation with airborne allergen in patients with atopic keratoconjunctivitis. AB - BACKGROUND: Atopic keratoconjunctivitis (AKC) is a chronic eye disease with periods of exacerbations. Many patients experience no obvious seasonal variation, although a majority of patients are allergic to common airborne allergens. OBJECTIVE: To investigate the allergic reaction, to conjunctival provocation with airborne allergens, in patients with AKC. METHODS: Eleven patients with AKC and birch and/or grass pollen allergy participated in the study, which was performed outside the pollen season. Five patients with seasonal allergic conjunctivitis (SAC) and five healthy subjects were included for validation purposes. The challenge was performed in one eye with the allergen, to which the patient was reactive, and with dilution buffer in the other eye. Signs and symptoms from both eyes were graded at baseline and at 10 min, 8 and 48 h after provocation. Tear fluid was collected from both eyes for cytokine analyses at baseline and at 8 and 48 h. RESULTS: A significant change in clinical symptoms and signs, (redness and chemosis) was evident 10 min after provocation compared with baseline (P = 0.005) and compared with the unprovoked eye (P = 0.005) in AKC subjects. These parameters were normalized after 8 and 48 h. A significant increase for IFN-gamma (P = 0.021) and IL-6 (P = 0.015), and a near significant increase for IL-10 (P = 0.066) were seen in the tear fluid of the challenged eye at 48 h after provocation vs. baseline and vs. the control eye for IFN-gamma (P = 0.005), IL-6 (P = 0.028) and IL-10 (P = 0.008) in AKC subjects. CONCLUSION AND CLINICAL RELEVANCE: In this single dose allergen provocation study, AKC patients responded with a typical IgE-mediated allergic reaction. An increase in cytokines at 48 h after the challenge was demonstrated and might, with further studies, give us a better understanding of the nature of inflammation in AKC. PMID- 22092653 TI - Histomorphometrical and molecular evaluation of endosseous dental implants sites in humans: correlation with clinical and radiographic aspects. AB - OBJECTIVE: To evaluate the correlations between clinical-radiographical aspects and histomorphometric-molecular parameters of endosseous dental implant sites in humans. MATERIAL AND METHODS: The study sample consisted of bone implant sites from the jawbones of 32 volunteers, which were classified according to two different systems: (1) based only on periapical and panoramic images (PP); (2) as proposed by Lekholm & Zarb (L&Z). Bone biopsies were removed using trephine during the first drilling for implant placement. Samples were stained with haematoxylin-eosin (HE), and histomorphometric analysis was performed to obtain the following parameters: trabecular thickness (Tb.Th), trabecular number, bone volume density (BV/TV), bone specific surface (BS/BV), bone surface density and trabecular separation (Tb.Sp). In addition, immunohistochemistry analysis was performed on bone tissue samples for the proteins, Receptor activator of nuclear factor kappa-B (RANK), RANK ligand (RANKL), osteoprotegerin (OPG) and Osteocalcin (OC). Also, the determination of the relative levels of gene expression was performed using Reverse transcription-real-time Polymerase Chain Reaction (RT PCR). RESULTS: PP and L&Z classification systems revealed a moderate correlation with BV/TV, BS/BV, Tb.Th and Tb.Sp. L&Z's system identified differences among bone types when BV/TV, BS/BV, Tb.Th and Tb.Sp were compared. A weak correlation between PP/L&Z classifications and the expression of bone metabolism regulators (RANK, RANKL, OPG e OC) was found. The analysis of mRNA expression showed no difference between the bone types evaluated. CONCLUSIONS: Our results suggest that PP and L&Z subjective bone-type classification systems are related to histomorphometric aspects. These data may contribute to the validation of these classifications. Bone remodelling regulatory molecules do not seem to influence morphological aspects of the jawbone . PMID- 22092654 TI - Immunohistochemical expression of Rho GTPases in ameloblastomas. AB - Rho GTPases are proteins that regulate cell cycle, shape, polarization, invasion, migration, and apoptosis, which are important characteristics of normal and neoplastic cells. Rho GTPases expression has been reported in normal tooth germ and several pathologies; however, it has not been evaluated in ameloblastomas. The aim of this study was to analyze the expression and distribution of RhoA, RhoB, Rac1, and Cdc42 Rho GTPases in solid and unicystic ameloblastomas. Three micrometer sections from paraffin-embedded specimens were evaluated by using an avidin-biotin immunohistochemical method with antibodies against the proteins mentioned above. RhoA and RhoB staining was observed in a high number of cells (P < 0.05) and greater intensity in non-polarized ones. Rac1 was not observed, and Cdc42 did not show any statistical differences between the number of non polarized and basal positive cells (P > 0.05). Upon comparing the studied ameloblastomas, a higher number of positive cells in the unicystic variant was observed than that in the solid one (P < 0,05). The results obtained suggest that these GTPases could play a role in the ameloblastoma neoplastic epithelial cell phenotype determination (polarized or non-polarized), as well as in variant (solid or unicystic) and subtype (follicular or plexiform) determination. Furthermore, they could participate in solid ameloblastoma invasion mechanisms. PMID- 22092656 TI - CT features of pleural masses and nodules. AB - Pleural space masses and nodules are rarely described on computed tomography (CT) in veterinary medicine and have only been described in patients with neoplasia. Our purpose was to describe the CT findings and diagnoses in seven patients with pleural masses and nodules. Two patients had broad-based, plaque-like pleural masses, both of which were due to neoplasia (primary pleural carcinoma, metastatic thymoma). Two patients had well-defined pleural nodules and nodular pleural thickening, one of which had mesothelial hypertrophy, and another of which had metastatic hemangiosarcoma. Three patients had ill-defined pleural nodules to nodular pleural thickening, one of which had metastatic pulmonary carcinoma, while the other two had bacterial infection with mesothelial proliferation (n = 2), fibrinous pleuritis (n = 1), and severe mediastinal pleuritis/mediastinitis (n = 2). Five of the seven patients had focal, multifocal or diffuse smooth, and/or irregular pleural thickening. Five of seven patients had pleural effusion, and postcontrast CT was useful in several patients for delineating the pleural lesions from the effusion. All patients except one had additional lesions identified on CT besides those in the pleural space. CT is useful in identifying and characterizing pleural space lesions and could be used to guide further diagnostic procedures such as thoracoscopy or exploratory thoracotomy. Both neoplastic and nonneoplastic diseases should be considered in the differential diagnoses for pleural space masses and nodules found on CT. PMID- 22092655 TI - Longitudinal relationship of early life immunomodulatory T cell phenotype and function to development of allergic sensitization in an urban cohort. AB - BACKGROUND: Immunomodulatory T cells are thought to influence development of allergy and asthma, but early life longitudinal data on their phenotype and function are lacking. OBJECTIVES: As part of the Urban Environment and Childhood Asthma (URECA) study, we investigated the development of immunomodulatory T cell phenotype and function, and characterized their relation to allergic disease progression from birth through to 2 years of age. METHODS: Immunomodulatory T cell phenotype and function in cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) at 1 and 2 years of age were characterized by analysing CD25(bright) and FoxP3(+) expression, proliferative responses and cytokine production. The relation of immunomodulatory T cell characteristics to allergic sensitization and disease at 1- and 2-years of age was investigated. RESULTS: The proportion of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+)T cells (n = 114, 83, 82 at birth, 1- and 2-years respectively) increased significantly, whereas there were no significant changes in the suppressive function of CD25(+)T cells (n = 78, 71, 81 at birth, 1- and 2-years respectively). Birth immunomodulatory T cell characteristics were not related to subsequent allergic sensitization or disease. However, increases in the numbers of CD4(+)CD25(bright) cells and their ability to suppress lymphoproliferative responses at 1 year of age were associated with reduced allergic sensitization at 1 (P = 0.03) and 2 (P = 0.02) years of age. Production of the anti-inflammatory cytokine IL-10 by CD25(+)T cells appeared to mediate this protective suppressive function. In contrast, by 2 years of age, we observed the emergence of a positive association of CD4(+)CD25(+) FoxP3(+) T cell numbers with allergic sensitization (P = 0.05) and eczema (P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest that the relationship between immunomodulatory T cell subsets, allergic sensitization and eczema is developmentally regulated. In the first year of life, CD4(+)CD25(+) IL-10 producing T cells are associated with a reduced incidence of allergic sensitization. Once allergic sensitization or eczema is established, CD4(+)CD25(+)FoxP3(+)T-reg cells expand to potentially counteract the allergic inflammatory response. Understanding the relationship between development of immunoregulatory T cells and early onset atopy could lead to new preventive strategies for allergic diseases. PMID- 22092657 TI - Development, ultrastructural pathology, and taxonomic revision of the Microsporidial genus, Pseudoloma and its type species Pseudoloma neurophilia, in skeletal muscle and nervous tissue of experimentally infected zebrafish Danio rerio. AB - The microsporidium Pseudoloma neurophilia was initially reported to infect the central nervous system of zebrafish causing lordosis and eventually death. Subsequently, muscle tissue infections were also identified. To understand the infection process, development, and ultrastructural pathology of this microsporidium, larval and adult zebrafish were fed P. neurophilia spores. Spores were detected in the larval fish digestive tract 3-h postexposure (PE). By 4.5-d PE, developing parasite stages were identified in muscle tissue. Wet preparations of larvae collected at 8-d PE showed aggregates of spores in the spinal cord adjacent to the notochord. All parasite stages, including spores, were present in the musculature of larval fish 8-d PE. Adult zebrafish sacrificed 45-d PE had fully developed infections in nerves. Ultrastructural study of the developmental cycle of P. neurophilia revealed that proliferative stages undergo karyokinesis, producing tetranucleate stages that then divide into uninucleate cells. The plasmalemma of proliferative cells has a previously unreported glycocalyx-like coat that interfaces with the host cell cytoplasm. Sporogonic stages form sporophorous vacuoles (SPOV) derived from the plasmalemmal dense surface coat, which "blisters" off sporonts. Uninucleate sporoblasts and spores develop in the SPOV. The developmental cycle is identical in both nerve and muscle. The SPOV surface is relatively thick and is the outermost parasite surface entity; thus, xenomas are not formed. Based on the new information provided by this study, the taxonomic description of the genus Pseudoloma and its type species, P. neurophilia, is modified and its life cycle described. PMID- 22092658 TI - Immediate rehabilitation of the edentulous mandible with screw type implants: results after up to 10 years of clinical function. AB - OBJECTIVES: The aim of this prospective case series was to evaluate the results of an immediate loading concept using four Xi VE S plus implants in the edentulous mandible, after a period of up to 10 years of clinical function. MATERIAL AND METHODS: Thirty patients were treated with four implants each placed interforaminally and provisionally restored within 1 week. Radiographic bone levels, condition of the peri-implant mucosa, implant survival and success were recorded annually from implant insertion (baseline) up to 10 years after final restoration. RESULTS: A total of 120 Xi VE S plus implants were placed in the interforaminal region. A significant coronal bone loss of 1.80 mm (SD +/- 0.65) was recorded within the first 8 years of function (P < 0.001). Within the next years no further significant increase of bone resorption was observed. The mean values of the plaque, calculus, bleeding and mucosal indices and probing depth remained low throughout this period. All implants were inserted with an insertion torque of more than 32 N cm. Two losses (1.7%) occurred prior to permanent restoration (1 and 3 months post-insertion), resulting in a survival rate of 98.3% over the entire observation period. Four implants were recorded as failures due to excessive bone resorption, resulting in an overall success rate of 95%. CONCLUSIONS: The results of this study indicate that in selected patients immediate restoration of dental implants in the edentulous mandible will achieve a clinically predictable outcome. PMID- 22092659 TI - Diversity and expression of different forms of RubisCO genes in polluted groundwater under different redox conditions. AB - Groundwater polluted with methyl-tert-butyl ether (MTBE) and ammonium was investigated for chemolithoautotrophic CO(2) fixation capabilities based on detailed analyses of ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) large subunit genes. Samples retrieved from a groundwater conditioning unit, characterized by different redox conditions, were examined for the presence of form IA, form IC (cbbL) and form II (cbbM) RubisCO genes and transcripts obtained from DNA- and RNA-extracts. Form IA RubisCO sequences, which revealed a complex and distinct variety in different sampling stations, were expressed in the original groundwater and in samples amended with oxygen, but not in the aquifer groundwater enriched with nitrate. Form IC RubisCO genes were exclusively detected in groundwater supplied with oxygen and sequences were affiliated with cbbL genes in nitrifying bacteria. cbbM genes were not expressed in the oxygen amended groundwater, probably due to the low CO(2) /O(2) substrate specificity of this enzyme. Most form II RubisCO transcripts were affiliated with RubisCO genes of denitrifiers, which are important residents in the groundwater supplied with nitrate. The distinct distribution pattern and diversity of RubisCO genes and transcripts obtained in this study suggest that the induction of different RubisCO enzymes is highly regulated and closely linked to the actual environmental conditions. PMID- 22092660 TI - The magnitude of intramuscular deoxygenation during exercise is an unreliable measure to diagnose the cause of leg pain. AB - We measured intramuscular oxygenation in the anterior tibial muscle of 176 patients with exercise-induced leg pain by noninvasive near-infrared spectroscopy before, during, and after an exercise test that elicited the symptoms. Clinical investigation was performed after each test. Intramuscular pressure was measured in patients with nonconclusive findings. Chronic anterior compartment syndrome (CACS) was diagnosed in 47 patients, and other causes for the leg pain were diagnosed in 129 patients by clinical means. The mean level of oxygenation decreased to 33 +/- 19% in patients with CACS and to 34 +/- 19% in patients without CACS compared with baseline level (100%) at rest before exercise. The level of oxygenation was below 20% during the exercise test in 12 of 47 (26%) patients with CACS and in 30 of 129 (23%) patients without CACS. The time required for reoxygenation after the cessation of exercise was 61 +/- 34 s in patients with CACS and 46 +/- 20 s in patients without CACS (P < 0.05). We conclude that the magnitude of intramuscular deoxygenation during exercise is an unreliable measure to diagnose CACS. However, the time for reoxygenation returning to baseline level following an exercise test is a valuable adjunct in diagnosing CACS. PMID- 22092661 TI - Granulomatous reaction to hyaluronic acid: a case series and review of the literature. PMID- 22092662 TI - Inferior alveolar nerve injury associated with implant surgery. AB - OBJECTIVES: Inferior alveolar nerve (IAN) is the most commonly injured nerve (64.4%) during implant treatment. At present, no standardized protocol exists for clinicians to manage IAN injury related with implant surgery. Therefore, the purposes of the present article were to analyze the reasons for nerve injury and to propose guidelines in managing IAN injury. MATERIAL AND METHODS: Patients with IAN sensory disturbances after implant treatment were recruited for the study. Sixteen patients, eight men and eight women, with a mean age of 52.2 +/- 8.1 years participated in this study. Patient examination, treatment, and IAN sensory function recovery monitoring were performed following six-step IAN injury during dental implant surgery (IANIDIS) protocol. The control group was composed of 25 healthy volunteers who never had IAN sensory disturbances or any trauma in the maxillofacial region. RESULTS: The IAN sensory disturbances were scored as following: 5 (31.25%) had hyperalgesia and 11 (68.75%) expressed hypoalgesia. The mean asymmetry index (AI) was calculated for each patient and varied from 0.6 to 3.2. Overall, 31.3% of nerve injury patients were classified as mild, 31.3% as moderate, and remaining 37.5% as severe injury. All patients were successfully treated with proposed IANIDIS protocol. CONCLUSION: The most frequent (50%) risk factor for IAN injury was intraoperative bleeding during bone preparation. The most common (56.3%) etiological risk factor of nerve injury was dental implant. A six-step protocol aimed at managing patients with IAN injury, during dental implant surgery, was a useful tool that could provide successful treatment outcome. PMID- 22092663 TI - Immunochemical studies of Salmonella Dakar and Salmonella Telaviv O-antigens (serogroup O:28). AB - Salmonella Dakar and Salmonella Telaviv bacteria belong to serogroup O:28, which represents 107 serovars and possesses only the epitope O28. Salmonella Telaviv has the subfactors O28(1) and O28(2) , whereas S. Dakar has O28(1) and O28(3) . So far, only limited serological and immunological information for this serogroup is available in the literature. Knowledge of the structures of their O polysaccharides and the immunochemical investigations performed in this work allowed to reveal the nature of subfactor O28(1) as attributed to the presence of 3-linked (or 3,4-disubstituted) alpha-d-GalpNAc in the main chains of S. Dakar and S. Telaviv O-polysaccharides. An explanation for the cross-reactions between Salmonella enterica O28 O-antigens and other Salmonella O-polysaccharides and their structural similarity to Escherichia coli O-serogroups is also given. PMID- 22092664 TI - Hydration measurements of the stratum corneum: comparison between the capacitance method (digital version of the Corneometer CM 825(r)) and the impedance method (Skicon-200EX(r)). AB - BACKGROUND: Measurement of stratum corneum (SC) hydration often involves the use of commercial instruments. The aim of this study was to compare and validate two recent instruments: the Corneometer 825(r) (digital probe) and the Skicon-200 EX(r). METHODS: In vitro calibration was carried out on filter pads using different solvents, measurements over different layers of plastic foils, and evaluation of desorption kinetics. In vivo measurements were carried out on skin sites covering a range of very dry to well-hydrated skin areas. RESULTS: Conductance measurements are influenced by electrolytes while capacitance measurements are not. Dielectric constant of the solvents influences the values of both instruments (r respectively 0.92 and 0.99). The capacitance method carries information from deeper layers (up to 45 MUm) compared with the conductance instrument (up to 15 MUm). Desorption experiments show a strong relation between the amount of water and respectively the capacitance and the conductance values. The in vivo experiments revealed a strong relation between the two methods (r = 0.97). Sensitivity of the capacitance method is limited for the highest hydration values. CONCLUSIONS: Both instruments allow a certain calibration and both give good estimates of the SC hydration. PMID- 22092665 TI - Validation of a Korean version of the Child Oral Health Impact Profile (COHIP) among 8- to 15-year-old school children. AB - OBJECTIVES: The purpose of this study was to assess reliability, discriminant validity, and convergent validity of the Oral Health Impact Profile (COHIP) Korean version in a representative community sample of 8- to 15-year-old Korean children. METHODS: A Korean version of COHIP was developed according to the standard procedure of cross-cultural adaptation of self-reported instruments. A representative community sample of 2236 schoolchildren was selected by cluster sampling method. RESULTS: Mean age of the participants was 11.8 years. Mean and median of the overall COHIP score were 103.3 (SD 13.3) and 106, respectively. Internal reliability and retest reliability were excellent with Chronbach's alpha 0.88 and intraclass correlation coefficient 0.88. Face validity was confirmed with 98% of participants reporting the COHIP questionnaire was easy to answer. Nonclinical factors such as self-rated oral health or satisfaction with oral health were significantly related with overall COHIP score and five subscale scores (P < 0.001) in a consistent manner. Children with carious permanent teeth and with orthodontic treatment need had highly significantly lower overall COHIP score (P < 0.01). CONCLUSION: The Korean version of the COHIP was successfully developed. The internal reliability, retest reliability, face validity, discriminant validity, and convergent validity of the COHIP Korean version were confirmed. PMID- 22092666 TI - Treatment of experimental periodontal disease with antimicrobial photodynamic therapy in nicotine-modified rats. AB - BACKGROUND: The aim of this study was to compare antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to scaling and root planing (SRP) for induced periodontitis in nicotine-modified rats. MATERIAL & METHODS: A total of 240 rats were evenly divided into two groups: C - saline solution treatment; N - nicotine treatment. Periodontal disease was induced in both groups at the first mandibular molar. After 7 days, the ligature was removed. All animals were submitted to SRP and were divided according to the following treatments: SRP - irrigation with saline solution; Toluidine Blue-O (TBO) - irrigation with phenothiazinium dye (100 MUg/ml); LLLT - laser irradiation (660 nm; 0.03 W; 4 J); and aPDT - TBO and laser irradiation. Ten animals in each group/treatment were euthanized at 7, 15 and 30 days. The histometric and immunohistochemical values were statistically analysed. RESULTS: Intragroup analysis demonstrated that in both groups the aPDT treatment resulted in lower bone loss (BL) when compared to SRP in all experimental periods. Intergroup analysis demonstrated that aPDT treatment resulted in lower BL in Group N than in Group C treated with SRP in all experimental periods. CONCLUSION: Antimicrobial photodynamic therapy was an effective adjunctive treatment to SRP for induced periodontitis in nicotine modified rats. PMID- 22092667 TI - Reactive oxygen and oxidative stress tolerance in plant pathogenic Pseudomonas. AB - Reactive oxygen species (ROS) are a key feature of plant (and animal) defences against invading pathogens. As a result, plant pathogens must be able to either prevent their production or tolerate high concentrations of these highly reactive chemicals. In this review, we focus on plant pathogenic bacteria of the genus Pseudomonas and the ways in which they overcome the challenges posed by ROS. We also explore the ways in which pseudomonads may exploit plant ROS generation for their own purposes and even produce ROS directly as part of their infection mechanisms. PMID- 22092668 TI - Haptoglobin and fibrinogen concentrations and leukocyte counts in the clinical investigation of caseous lymphadenitis in sheep. AB - BACKGROUND: Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis (CLA), a disease that affects small ruminants and is responsible for economic losses, including condemnation of carcasses and damaged hides. OBJECTIVE: The goal of this study was to determine if serum haptoglobin and plasma fibrinogen concentrations and peripheral blood leukocyte counts are biologic markers of CLA in sheep. METHODS: Blood from 38 clinically healthy Santa Ines ewes selected and segregated from a commercial flock of 2500 sheep in an area endemic for C. pseudotuberculosis was collected every 30 days for 6 months. An indirect ELISA was used to detect IgM and IgG antibodies against C. pseudotuberculosis. Serum haptoglobin concentration was measured using a hemoglobin-binding assay and plasma fibrinogen concentration by refractometry following heat precipitation. Total leukocyte counts were determined using a hemocytometer, and differential leukocyte counts were performed on smears of peripheral blood. RESULTS: Twenty-one sheep were seropositive at the start of the study; 15 became seropositive during the study. Only 2 sheep were seronegative at the conclusion of the study. Haptoglobin and fibrinogen concentrations and WBC counts were not significantly different for seropositive and seronegative animals. Nine sheep, 5 that were seropositive positive at the start and 4 that became seropositive during the study period, developed abscesses in peripheral lymph nodes. There were 15 animals that became seropositive during the study, and their values did not differ significantly among the 3 phases--seronegative, acute (IgM+/IgG+/-), and chronic (IgM-/IgG+)--of infection. However, 11 of these sheep did not develop peripheral abscesses and had significantly higher haptoglobin concentrations and lower monocyte counts during the acute phase of the disease than did the 4 sheep that later developed abscesses. CONCLUSION: Serum haptoglobin concentration and monocyte counts may be potential markers for progression of CLA in sheep. PMID- 22092669 TI - Skin hydration and cooling effect produced by the Voltaren(r) vehicle gel. AB - BACKGROUND: Voltaren vehicle gel is the carrier substance of the topical Voltaren products. This vehicle gel is especially formulated to be easily applied on the skin, while providing some sensory benefits. The present study aims to substantiate the widely perceived hydrating and cooling effect of Voltaren vehicle gel. METHODS: Volar forearm skin hydration and transepidermal water loss (TEWL) were measured and user satisfaction was evaluated by questionnaires, after application in 31 healthy, female volunteers. The cooling effect was investigated for 40 min with thermal imaging on 12 forearm sites of six healthy subjects. RESULTS: Voltaren vehicle gel application increased skin hydration by 13.1% (P = 0.0002) when compared with the untreated site, 8 h after the final treatment after 2 weeks. TEWL decreased on both treated (0.37 g/m(2) /h) and untreated (0.74 g/m(2) /h) forearm sites after 2 weeks (8 h after last treatment), demonstrating a relative increase of 6.5% in water loss. Voltaren vehicle gel application resulted in a rapid reduction of skin surface temperature by 5.1 degrees C after only 3 min with an average maximum reduction of 5.8 degrees C after 10 min. The cooling effect was experienced by 94% subjects, while 74% felt that their skin became softer. No adverse events, including skin irritation, were reported during the study and by the 37 participants. CONCLUSION: This study showed a statistically significant increase in skin hydration as well as a rapid cooling effect lasting approximately 30 min, after application of Voltaren vehicle gel. The small relative increase in water loss may be attributed to an additional skin surface water loss secondary to the increased water content brought into the skin by the Voltaren vehicle gel. The use did not induce any skin irritation and was found acceptable to use by the majority of participants. PMID- 22092670 TI - Bone modelling at fresh extraction sockets: immediate implant placement versus spontaneous healing: an experimental study in the beagle dog. AB - OBJECTIVES: The purpose of this investigation is to describe histologically the undisturbed healing of fresh extraction sockets when compared to immediate implant placement. METHODS: In eight beagle dogs, after extraction of the 3P3 and 4P4, implants were inserted into the distal sockets of the premolars, while the mesial sockets were left to heal spontaneously. Each animal provided four socket sites (control) and four implant sites (test). After 6 weeks, animals were sacrificed and tissue blocks were dissected, prepared for ground sectioning. RESULTS: The relative vertical buccal bone resorption in relation to the lingual bone was similar in both test and control groups. At immediate implant sites, however, the absolute buccal bone loss observed was 2.32 (SD 0.36) mm, what may indicate that while an apical shift of both the buccal and lingual bone crest occurred at the implant sites, this may not happen in naturally healing sockets. CONCLUSIONS: The results from this investigation showed that after tooth extraction the buccal socket wall underwent bone resorption at both test and control sites. This resorption appeared to be more pronounced at the implant sites, although the limitations of the histological evaluation method utilized preclude a definite conclusion. PMID- 22092671 TI - Sex difference in fluid balance responses during prolonged exercise. AB - Maintaining a proper fluid balance is important during exercise as athletes are prone to develop dehydration during exercise. Although several factors may regulate the fluid balance, little is known about the role of sex during prolonged moderate-intensity exercise. Therefore, we compared body mass changes and fluid balance parameters in men vs women in a large heterogeneous group of participants during prolonged exercise. Ninety-eight volunteers walked 30-50 km at a self-selected pace. Exercise duration (8 h, 32 min) and intensity (69% HRmax) were comparable between groups. Men demonstrated a significantly larger change in body mass than women (-1.6% vs -0.9%, respectively, P < 0.001) and a higher incidence of dehydration (defined as >= 2% body mass loss) compared with women (34% vs 12%, respectively, odds ratio = 4.2, 95% CI = 1.1-16.7). Changes in blood sodium levels were significantly different between men (+1.5 mmol/L) and women (-0.4 mmol/L), while 27% of the men vs 0% of the women showed postexercise hypernatremia (sodium levels >= 145 mmol/L). Moreover, men demonstrated a significantly lower fluid intake (2.9 mL/kg/h) and higher fluid loss (5.0 mL/kg/h) compared with women (3.7 and 4.8 mL/kg/h, respectively). Taken together, our data suggest that men and women demonstrate different changes in fluid balance in response to a similar bout of exercise. PMID- 22092672 TI - The aberdeen knot: a sliding knot for dermatology. PMID- 22092673 TI - HIV-1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy. AB - Matrix metalloproteinases (MMPs) are implicated in diverse processes, such as neuroinflammation, leakiness of the blood-brain barrier (BBB) and direct cellular damage in neurodegenerative and other CNS diseases. Tissue destruction by MMPs is regulated by their endogenous tissue inhibitors (TIMPs). TIMPs prevent excessive MMP-related degradation of extracellular matrix components. In a rat model of human immunodeficiency virus (HIV)-related encephalopathy, we described MMP-2 and MMP-9 upregulation by HIV-1 envelope gp120, probably via gp120-induced reactive oxygen species. Antioxidant gene delivery blunted gp120-induced MMP production. We also studied the effect of gp120 on TIMP-1 and TIMP-2 production. TIMP-1 and TIMP-2 levels increased 6 h after gp120 injection into rat caudate-putamen (CP). TIMP-1 and TIMP-2 colocalized mainly with neurons (92 and 95%, respectively). By 24 h, expression of these protease inhibitors diverged, as TIMP-1 levels remained high but TIMP-2 subsided. Gene delivery of the antioxidant enzymes Cu/Zn superoxide dismutase or glutathione peroxidase into the CP before injecting gp120 there reduced levels of gp120-induced TIMP-1 and TIMP-2, recapitulating the effect of antioxidant enzymes on gp120-induced MMP-2 and MMP-9. A significant correlation was observed between MMP/TIMP upregulation and BBB leakiness. Thus, HIV-1 gp120 upregulated TIMP-1 and TIMP-2 in the CP. Prior antioxidant enzyme treatment mitigated production of these TIMPs, probably by reducing MMP expression. PMID- 22092674 TI - Use of fraction flow reserve to predict changes over time in management of superficial femoral artery. AB - BACKGROUND: Peripheral arterial disease is a condition characterized by progressive arterial narrowing, which affects patients' quality of life. The purposes of this study were to (1) establish the feasibility of obtaining peripheral fractional flow reserve (pFFR) in the peripheral vascular circulation, (2) demonstrate an association between baseline pFFR and peak systolic velocity (PSV) measured by duplex ultrasound, and (3) correlate postintervention pFFR with future restenosis using the change in PSV over time as a surrogate. METHODS: Twenty patients underwent baseline ankle brachial index (ABI) and PSV testing. Pre- and postintervention pFFR was performed. Patients were followed with three ABI and PSV recordings during the 1 year follow-up period. The association between baseline PSV, ABI, and pFFR with changes in PSV over time were explored. Predictors of postprocedural PSV over time were determined. RESULTS: The baseline translesional-resting ratio was significantly different from the pFFR using adenosine (0.79 +/- 0.08 vs. 0.71 +/- 0.09, P = 0.01). Baseline PSV was significantly associated with preintervention pFFR (-0.77, P < 0.001). Compared to patients with a postprocedure pFFR > 0.95, patients with a postprocedure pFFR < 0.95 had a significantly more rapid rise in PSV over time (P = 0.009). CONCLUSION: This is the first study to demonstrate that the peripheral vascular bed does respond to vasodilatation thereby supporting the use of pFFR for this procedure. In our study, postintervention pFFR < 0.95 predicted a more rapid increase in PSV over time, which is a reasonably accepted surrogate for restenosis. PMID- 22092676 TI - Reliability and failure modes of anterior single-unit implant-supported restorations. AB - PURPOSE: Failures of implant-abutment connections have been observed clinically, especially in single-tooth replacements. This study sought to evaluate the reliability and failure modes of implant-supported anterior crowns restored with different implant systems. MATERIALS AND METHODS: Forty-two Ti-6Al-4V dental implants (~4 mm diameter) were used for single anterior crown replacement and divided into two groups according to tested system: (NB) Replace Select system, Nobel Biocare (n = 21); and (IL) Internal connection system, Intra-Lock International (n = 21). Proprietary abutments were screwed to the implants and anatomically correct maxillary central incisor metal crowns were cemented and subjected to step-stress-accelerated life testing in water. Use-level probability Weibull curves and reliability for a mission of 50,000 cycles at 200 N (95% 2 sided confidence intervals) were calculated. Polarized-light and scanning electron microscopes were used for failure analyses. RESULTS: The Beta values for NB and IL (2.09 and 2.05, respectively) indicated that fatigue accelerated the failure of both groups. The calculated reliability for the NB system (0.81) was lower than for the IL system (0.96), but no significant difference was observed between groups. Screw and abutment fracture was the chief failure mode in group NB, while screw fracture was most representative in specimens of group IL. CONCLUSIONS: Reliability of implant-supported maxillary central incisor crowns was not significantly different between NB and IL abutments. Failure modes differed between implant systems. PMID- 22092675 TI - Anaphylaxis in Turkish children: a multi-centre, retrospective, case study. AB - BACKGROUND: Anaphylaxis is a serious and potentially lethal systemic reaction affecting more than one organ or system. OBJECTIVE: We aimed to describe the demographic characteristics, clinical features, causes, settings, and administered therapy in Turkish children. METHODS: This retrospective, case note study included all children referred to the outpatient clinics of the Pediatric Allergy Departments of the participating study centres from 1 July 1999 to 30 June 2009 for investigation of anaphylaxis or who were seen by us at the moment of the reaction during the same period and who met the clinical criteria of anaphylaxis. RESULTS: Two hundred and twenty-four cases of anaphylaxis were reported in 137 children (88 boys, P = 0.0001). The mean +/- SD age at the referral was 7.7 +/- 4.2 years (range: 4 months-17 years). Ninety-eight episodes (43.8%) occurred at home. The symptoms were cutaneous in 222 (99.1%) episodes, respiratory in 217 (96.9%), neuro-psychiatric in 118 (52.7%), cardiovascular in 92 (41.1%), and gastrointestinal in 88 (39.3%). Biphasic reaction was reported in seven episodes (3.1%, 95% CI: 1.5-6.3). Death occurred in one case (0.4%, 95% CI: 0.08-2.4). Treatment was available in 158 episodes (70.5%). Of them, 148 (93.7%) received antihistamines, 132 (83.5%) corticosteroids, 51 (32.3%) epinephrine, and 17 (10.8%) beta-2-mimetics. The causative agents were foods in 86 (38.4%) episodes, hymenoptera venom in 84 (37.5%), drugs and medications in 47 (21.0%), and latex in 5 (2.2%). In two episodes (0.9%), the causative agent was unidentified. Allergy to the trigger was known prior to anaphylaxis in 116 (51.8%) episodes. An epinephrine auto-injector had been prescribed for 70 children (51.1%). CONCLUSIONS AND CLINICAL RELEVANCE: Anaphylaxis was seen significantly more in boys. Most of the reactions occurred at home. Foods were the most frequent cause. Epinephrine, the first-line treatment of anaphylaxis, was administered in only a third of the children. PMID- 22092677 TI - Complete mitochondrial genome sequence of the phytopathogenic fungus Penicillium digitatum and comparative analysis of closely related species. AB - The complete mitochondrial genome of Penicillium digitatum (Pers.:Fr) Sacc is reported, the first time in a phytopathogenic Penicillium species. Comparative analysis revealed its close relationship to mitochondrial genomes of other Penicillium and Aspergillus species, both in gene content and in arrangement. The intron content of protein coding genes revealed several differences. The different exon-intron organization of Cytochrome Oxidase Subunit 1 genes indicated their common origin before the divergence of Penicillium and Aspergillus, and that, largely, their introns were transmitted vertically. PMID- 22092678 TI - Pseudomonas syringae pv. phaseolicola effector HopF1 inhibits pathogen-associated molecular pattern-triggered immunity in a RIN4-independent manner in common bean (Phaseolus vulgaris). AB - Plant pathogens usually promote pathogenesis by secreting effector proteins into host plant cells. One of the secreted effectors of Pseudomonas syringae pv. phaseolicola, the causative agent of halo-blight disease in common bean (Phaseolus vulgaris), HopF1, activates effector-triggered immunity (ETI) in a bean cultivar containing R1 resistance gene, but displays virulence function in a bean cultivar without the R1 gene. The virulence mechanism of the effector remained unknown, although it was identified more than a decade ago. Here we demonstrated that HopF1 can inhibit pathogen-associated molecular pattern triggered immunity (PTI) in a susceptible bean cultivar Tendergreen. HopF1 directly interacted with two RPM1-interacting protein 4 (RIN4) orthologs of bean, PvRIN4a and PvRIN4b. Like RIN4 in Arabidopsis, both PvRIN4 orthologs negatively regulated the PTI responses in bean. However, the virulence function of HopF1 was enhanced in Tendergreen silencing PvRIN4. Furthermore, silencing PvRIN4a compromised the avrbeta1-induced hypersensitive response (HR), which previously was reported to be suppressed by HopF1. Together, these results demonstrated that PvRIN4 orthologs were not the virulence target of HopF1 for inhibiting PTI, but probably for interfering with ETI. PMID- 22092679 TI - Adherence and motility characteristics of clinical Acinetobacter baumannii isolates. AB - Acinetobacter baumannii continues to be a major health problem especially in hospital settings. Herein, features that may play a role in persistence and disease potential were investigated in a collection of clinical A. baumannii strains from Australia. Twitching motility was found to be a common trait in A. baumannii international clone I strains and in abundant biofilm formers, whereas swarming motility was only observed in isolates not classified within the international clone lineages. Bioinformatic analysis of the type IV fimbriae revealed a correlation between PilA sequence homology and motility. A high level of variability in adherence to both abiotic surfaces and epithelial cells was found. We report for the first time the motility characteristics of a large number of A. baumannii isolates and present a direct comparison of A. baumannii binding to nasopharyngeal and lung epithelial cells. PMID- 22092680 TI - In vitro activity of deferoxamine against Porphyromonas gingivalis. AB - Deferoxamine (DFO), an FDA-approved iron chelator used for treatment of iron poisoning, affects bacteria as iron availability is intimately connected with growth and several virulence determinants. However, little is known about the effect on oral pathogens. In this study, the effect of DFO on Porphyromonas gingivalis, a major periodontopathogen which has an essential growth requirement for hemin (Fe(3+)-protoporphyrin IX), was evaluated. The viability of P. gingivalis W83 was not affected by 0.06-0.24 mM DFO, whereas the doubling time of the bacterium was considerably prolonged by DFO. The inhibitory effect was evident at earlier stages of growth and reduced by supplemental iron. UV-visible spectra using the pigments from P. gingivalis cells grown on blood agar showed that DFO inhibited MU-oxo bisheme formation by the bacterium. DFO decreased accumulation and energy-driven uptake of hemin by P. gingivalis. Antibacterial effect of H(2)O(2) and metronidazole against P. gingivalis increased in the presence of DFO. Collectively, DFO is effective for hemin deprivation in P. gingivalis suppressing the growth and increasing the susceptibility of the bacterium to other antimicrobial agents such as H(2)O(2) and metronidazole. Further experiments are necessary to show that DFO may be used as a therapeutic agent for periodontal disease. PMID- 22092681 TI - Cloning and expression of serum opacity factor in fish pathogenic Streptococcus dysgalactiae and its application to discriminate between fish and mammalian isolates. AB - Lancefield group C Streptococcus dysgalactiae (GCSD) is known as a causative agent of bovine mastitis and cardiopulmonary diseases in humans. Recently, GCSD has been isolated from diseased fish in Japan. Almost all culture supernatants and sodium dodecyl sulfate extracts obtained from GCSD isolated from farmed fish possessed serum opacity activity. Serum opacity factor (SOF) is a bifunctional cell-associated protein that causes serum opacification. In this study, a gene coding SOF, which was named sof-FD, was identified from GCSD isolated from fish. The amino acid sequence of sof-FD showed 40.1-46.5% identity to those of other SOFs from mammalian strains of S. dysgalactiae and Streptococcus pyogenes. Repetitive fibronectin binding domains were also observed in sof-FD, the structures of which were similar to those of other SOFs, as previously reported. The amino acid sequence of SOF was identical among fish isolates. A primer set targeting the sof-FD gene was designed and applied to a PCR assay for discriminating fish isolates from mammalian isolates. PMID- 22092682 TI - BopC is a type III secreted effector protein of Burkholderia pseudomallei. AB - Burkholderia pseudomallei, the causative agent of melioidosis, exploits the Bsa type III secretion system (T3SS) to deliver effector proteins into host cells. These effectors manipulate host cell functions; thus, contributing to the ability of the bacteria to evade the immune response and cause disease. Only two Bsa secreted effectors have been conclusively identified to date. Here, we report the identification of the third B. pseudomallei type III secreted effector protein, designated BopC. BopC is encoded by the bpss1516 gene abutting bpss1517, which encodes its putative chaperone. The genes are located in the close proximity to the bsa T3SS gene cluster of B. pseudomallei K96243 (Fig. 1). BopC was secreted into culture supernatant by the wild-type B. pseudomallei strain, but its secretion was abolished in the bsaZ T3SS mutant. Using pull down and co purification assays, we confirmed that BopC interacts with its putative chaperone, BPSS1517, in vitro. Furthermore, the first 20 N-terminal amino acids of BopC were found to be sufficient to mediate the T3SS-dependent translocation of a reporter protein from a heterologous enteropathogenic Escherichia coli host into mammalian cells. Finally, bopC mutant was found to be less invasive than the wild-type strain in the epithelial cells. PMID- 22092683 TI - Lactobacillus alvi sp. nov., isolated from the intestinal tract of chicken. AB - Strain R54(T) was isolated from the gizzard of hens. The isolate was Gram positive, facultative anaerobic, gas-forming, catalase-negative, nonmotile, nonspore-forming and short-rod-shaped. The optimal temperature for growth was 40 degrees C and the DNA G+C content was 42.7 mol%. The 16S rRNA gene sequences similarity showed that strain R54(T) was most closely related to Lactobacillus ingluviei LMG 20380(T) (97.5%), followed by Lactobacillus coleohominis CIP 106820(T) (96.1%), Lactobacillus secaliphilus DSM 17896(T) (95.6%) and Lactobacillus gastricus LMG 22113(T) (95.4%). The DNA-DNA relatedness between strain R54(T) and L. ingluviei LMG 20380(T) , was 43.3%. The predominant cellular fatty acids of strain R54(T) were C(18:1 omega9c) (64.9%) and C(16:0) (20.0%), and the major polar lipid group was phospholipids. On the basis of polyphasic taxonomy approach, strain R54(T) represents a novel species of the genus Lactobacillus, for which the name Lactobacillus alvi sp. nov. is proposed (type strain R54(T) = KCCM 90099(T) = JCM 17644(T)). PMID- 22092684 TI - Induction of the Escherichia coli cysK gene by genetic and environmental factors. AB - Cysteine synthase A encoded by cysK catalyzes the synthesis of cysteine from O acetylserine. Expression of cysK in Escherichia coli is under the control of CysB, a LysR family transcription factor. Herein we showed that the expression of cysK is regulated by several genetic and environmental factors in addition to CysB: two genetic factors, OmpR and CysE, and lithium. Based on the findings, we constructed the high-level expression system of cysK. PMID- 22092685 TI - Effect of glucocorticoid administration on adrenal gland size and sonographic appearance in beagle dogs. AB - Our aim was to evaluate the influence of glucocorticoids on the adrenal gland using ultrasonography. Eleven healthy beagles were used in a prospective placebo controlled study. All dogs received hydrocortisone at 10 mg/kg twice a day per os for 4 months or a gelatin capsule twice a day per os as a placebo. Clinical and endocrinologic examination of the dogs and ultrasonographic evaluation of adrenal echogenicity, shape, and measurement of the length and height of the cranial and caudal pole were performed at baseline (TO), at 1 (T1) and 4 months (T4) after the beginning of treatment, and 2 months after the end of the treatment including 1 month of tapering and 1 month without treatment (T6). The dogs were assigned randomly to the glucocorticoid (n = 6) and placebo groups (n = 5). At T1, the difference between the two groups for the height of the cranial and caudal pole was not ultrasonographically remarkable despite a statistically significant difference (P = 0.0165 and P = 0.0206). Decreased height and length of entire gland were observed at T4 (P < 0.0001, P = 0.0015, and P = 0.0035, respectively). Percentages of atrophy were variable between dogs. Both adrenal glands regained normal size and shape 1 month after cessation of glucocorticoid administration. As not all dogs developed marked adrenal gland atrophy and the degree of atrophy varied widely between individuals, ultrasonography cannot be the technique of choice to detect iatrogenic hypercortisolism. Ultrasonographic changes are reversible within 1 month after the end of glucocorticoid administration. PMID- 22092686 TI - Serum bone formation marker correlation with improved osseointegration in osteoporotic rats treated with simvastatin. AB - OBJECTIVE: Simvastatin has been shown to enhance osseointegration of pure titanium implants in osteoporotic rats. This study aimed to evaluate the relationship between the serum level of bone formation markers and the osseointegration of pure titanium implants in osteoporotic rats treated with simvastatin. MATERIALS AND METHODS: Fifty-four female Sprague-Dawley rats, aged 3 months, were randomly divided into three groups: Sham-operated group (SHAM; n = 18), ovariectomized group (OVX; n = 18), and ovariectomized with simvastatin treatment group (OVX + SIM; n = 18). Fifty-six days after ovariectomy, screw shaped titanium implants were inserted into the tibiae. Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX + SIM group. The animals were killed at either 28 or 84 days after implantation and the undecalcified tissue sections were processed for histological analysis. Total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP) and bone Gla protein (BGP) were measured in all animal sera collected at the time of euthanasia and correlated with the histological assessment of osseointegration. RESULTS: The level of ALP in the OVX group was higher than the SHAM group at day 28, with no differences between the three groups at day 84. The level of BALP in the OVX + SIM group was significantly higher than both OVX and SHAM groups at days 28. Compared with day 28, the BALP level of all three groups showed a significant decrease at day 84. There were no significant differences in BGP levels between the three groups at day 28, but at day 84, the OVX + SIM group showed significantly higher levels than both the OVX and SHAM groups. There was a significant increase in BGP levels between days 28 and 84 in the OVX + SIM group. The serum bone marker levels correlated with the histological assessment showing reduced osseointegration in the OVX compared to the SHAM group which is subsequently reversed in the OVX + SIM group. CONCLUSION: The results from this study indicate that the serum level of bone formation markers, especially BALP and BGP, could be correlated with the degree of osseointegration around titanium implants in osteoporotic rats treated with simvastatin. PMID- 22092687 TI - Post-mating prezygotic barriers to gene exchange between hybridizing field crickets. AB - Studies of sexual selection in speciation have traditionally focused on mate preference, with less attention given to traits that act between copulation and fertilization. However, recent work suggests that post-mating prezygotic barriers may play an important role in speciation. Here, we evaluate the role of such barriers in the field crickets, Gryllus firmus and Gryllus pennsylvanicus. Gryllus pennsylvanicus females mated with G. firmus males produce viable, fertile offspring, but when housed with both species produce offspring sired primarily by conspecifics. We evaluate patterns of sperm utilization in doubly mated G. pennsylvanicus females and find no evidence for conspecific sperm precedence. The reciprocal cross (G. firmus female * G. pennsylvanicus male) produces no progeny. Absence of progeny reflects a barrier to fertilization rather than reduced sperm transfer, storage or motility. We propose a classification scheme for mechanisms underlying post-mating prezygotic barriers similar to that used for premating barriers. PMID- 22092688 TI - Efficacy of pulsed electromagnetic energy in postoperative recovery from blepharoplasty. AB - BACKGROUND: A novel medical device that has been approved by the Food and Drug Administration is available for treatment of postsurgical edema. The device emits a low-level, pulsed electromagnetic energy field, which modulates resting cell membrane potential, allowing a return to physiologic resting membrane potential. OBJECTIVE: To investigate the benefits of electromagnetic energy in eyelid wound healing. METHODS: Fifty-seven individuals participated in this randomized, double blinded study. All patients underwent upper blepharoplasty. At the postoperative visit, patients rated pain, edema, and ecchymosis, and the physician rated edema, ecchymosis, and erythema. RESULTS: There was no difference (p = .76) in patient pain rating when comparing placebo (1.6) with the patch (1.3). Patients reported 6% less edema (p = .11) and 10% less ecchymosis (p = .17) with the active patch eye than in control eye. The physician-graded edema, ecchymosis, and erythema had a mean Likert-type scale difference between placebo and active eyes of -0.3 (p = .12), -0.3 (p = .17), and -0.2 (p = .004) respectively. CONCLUSION: The use of pulsed electromagnetic energy did not have an effect on postoperative pain, edema, or ecchymosis as rated by patients and physicians. There was a statistically significant reduction in physician-graded erythema for active patch eyes versus placebo. PMID- 22092689 TI - Osseointegration in periodontitis susceptible individuals. AB - OBJECTIVES: The aim of the present study was to examine tissue integration of implants placed (i) in subjects who had lost teeth because of advanced periodontal disease or for other reasons, (ii) in the posterior maxilla exhibiting varying amounts of mineralized bone. MATERIAL AND METHODS: Thirty-six subjects were enrolled; 19 had lost teeth because of advanced periodontitis (group P) while the remaining 17 subjects had suffered tooth loss from other reasons (group NP). As part of site preparation for implant placement, a 3 mm trephine drill was used to remove one or more 2 mm wide and 5-6 mm long block of hard tissue [biopsy site; Lindhe et al. (2011). Clinical of Oral Implants Research, DOI: 10.1111/j.1600-0501.2011.02205.x]. Lateral to the biopsy site a twist drill (diameter 2 mm) was used to prepare the hard tissue in the posterior maxilla for the placement of a screw-shaped, self-tapping micro-implant (implant site). The implants used were 5 mm long, had a diameter of 2.2 mm. After 3 months of healing, the micro-implants with surrounding hard tissue cores were retrieved using a trephine drill. The tissue was processed for ground sectioning. The blocks were cut parallel to the long axis of the implant and reduced to a thickness of about 20 MUm and stained in toluidine blue. The percentage of (i) implant surface that was in contact with mineralized bone as well as (ii) the amount of bone present within the threads of the micro-implants (percentage bone area) was determined. RESULTS: Healing including hard tissue formation around implants placed in the posterior maxilla was similar in periodontitis susceptible and non-susceptible subjects. Thus, the degree of bone-to-implant contact (about 59%) as well as the amount of mineralized bone within threads of the micro implant (about 45-50%) was similar in the two groups of subjects. Pearson's coefficient disclosed that there was a weak negative correlation (-0.49; P < 0.05) between volume of fibrous tissue (biopsy sites) and the length of bone to implant contact (BIC) while there was a weak positive correlation (0.51; P < 0.05) between the volume of bone marrow and BIC. PMID- 22092690 TI - Recruitment order of the abdominal muscles varies with postural task. AB - Abdominal muscle recruitment strategies in response to a postural perturbation contradict the theory that the deeper abdominal muscles are always recruited in advance of the more superficial muscles. The purpose of this study was to determine whether such contrasting muscle recruitment patterns are due to the postural task or the predictability of a postural task. Participants performed an arm raise task as well as an unpredictable and a predictable balance perturbation task (i.e. support-surface translation) while intramuscular electromyographic (EMG) recordings were obtained from the deep [transversus abdominis (TrA)] and superficial [obliquus externus (OE)] abdominal muscles. The abdominal muscle recruitment order was dependent on the postural task but not on the predictability of a postural perturbation. Whereas arm raises elicited similar EMG onset latencies in TrA and OE, the OE onset latency was 48 ms earlier than the TrA following an unpredictable translation (P = 0.003). The early OE activation persisted when the translation was made predictable to the participant (P = 0.024). These results provide evidence that the abdominal muscle recruitment order varies with the trunk stability requirements specific to each task. Rehabilitation strategies focusing on an early TrA activation to improve postural stability may not be appropriate for all everyday tasks. PMID- 22092691 TI - Evaluation of moldable, in situ hardening calcium phosphate bone graft substitutes. AB - OBJECTIVE: Moldable in situ self-stabilizing and hardening bone graft materials facilitate handling and may be suitable for membrane-free bone regeneration methods. This study aimed to compare two moldable synthetic calcium phosphate materials in a rabbit calvarial defect model. METHOD: In 12 New Zealand white rabbits, four evenly distributed 6 mm diameter defects were drilled in the calvarial bone. Three filler materials were randomly applied to 48 defects: an in situ hardening polylactide-coated beta-tricalcium phosphate (TCP), an in situ hardening polylactide-coated biphasic calcium phosphate (BCP), and a granular deproteinized bovine bone matrix (DBBM, positive control). One defect remained untreated and served as a negative control. Six animals were sacrificed after 4 weeks, and the remaining animals were sacrificed after 16 weeks. Biocompatibility, bone graft substitute integration and resorption, bone formation, defect bridging, and height of reconstructed hard tissue were assessed histologically and histomorphometrically. RESULTS: All tested materials showed good biocompatibility. Semi-quantitative analysis and pair-wise comparison suggested that BCP was more efficient in centripetal bone formation when compared with TCP. After 4 weeks, significantly more bone had formed in the defects treated with either TCP or BCP materials compared with the untreated sites. BCP and DBBM did not show macroscopic signs of degradation, whereas the TCP material was partially resorbed after 16 weeks. Otherwise, no major differences were detected between the three materials. CONCLUSION: The moldable, synthetic calcium phosphates are safe and suitable bone graft substitutes with outcomes that are comparable to the control material. PMID- 22092692 TI - Treatment and secondary prevention effects of the probiotics Lactobacillus paracasei or Bifidobacterium lactis on early infant eczema: randomized controlled trial with follow-up until age 3 years. AB - BACKGROUND: Allergic disease has been associated with altered intestinal microbiota. Therefore, probiotics have been suggested as a potential treatment for eczema. OBJECTIVE: We investigated whether dietary supplementation of infants with eczema at age 3-6 months with Lactobacillus paracasei CNCM I-2116 or Bifidobacterium lactis CNCM I-3446 had a treatment effect or altered allergic disease progression. METHODS: Primary outcome included eczema severity (SCORing Atopic Dermatitis, SCORAD) 3 months post-randomization. Secondary: SCORAD (other visits); infant dermatitis quality of life (IDQoL); gastrointestinal permeability; urinary eosinophilic protein X; allergen-sensitization; allergic symptoms (age 12, 18, 36 months). A total of 208 infants aged 3-6 months with physician-diagnosed eczema were recruited; 137/208 (SCORAD >= 10, consuming >= 200 mL standard formula/day) were randomized to daily supplements containing L. paracasei or B. lactis or placebo for a 3-month period, while receiving extensively hydrolysed whey-formula (dairy-free diet). There were two open observational groups, one group exclusively breastfed (n = 22) and the other, standard formula-fed (n = 49). TRIAL NUMBER: ISRCTN41490500. RESULTS: Eczema severity decreased significantly over time in all groups. No significant difference was observed between randomized groups after 12-week treatment-period (SCORAD-score pre-/post-intervention: B. lactis 25.9 [95% CI: 22.8-29.2] to 12.8 [9.4-16.6]; L. paracasei 25.4 [22.1-29] to 12.5 [9.2-16.4]; placebo 26.9 [23.4 30.6] to 11.8 [9.6-14.3]; P = 0.7). Results were similar when analysis was controlled for allergen-sensitization, or when only sensitized infants were analysed. No differences were found for secondary outcomes. No difference was observed in SCORAD-score between randomized and observational groups. CONCLUSION AND CLINICAL RELEVANCE: We found no benefit from supplementation with B. lactis or L. paracasei in the treatment of eczema, when given as an adjunct to basic topical treatment, and no effect on the progression of allergic disease from age 1 to 3 years. PMID- 22092693 TI - Non-syndromic multiple supernumerary teeth: meta-analysis. AB - BACKGROUND: Non-syndromic multiple supernumerary teeth (NSMST) is a condition with a very low prevalence and which is opportunely described in the literature by case reports or group of cases. This represents a problem when it comes to describing and discussing the characteristics of this disorder. MATERIALS AND METHODS: A search was conducted in PubMed, Web of Knowledge, Science Direct, and Scopus databases to locate and identify cases and series of cases about articles on multiple supernumerary teeth not associated with syndromes that have been reported so far. The following data were recorded: age, gender, total number of supernumerary teeth, number of teeth in both the maxilla and mandible, respectively, and number of teeth in each dental series (incisor, canine premolar, and molar). Bilaterality in dental series and its localization in either maxilla or mandible were also determined. RESULTS: A total of 46 cases including patients of both genders with a mean age of 19 years (SD = 6.826) and a ratio of 2.14:1 were identified. A total of 393 supernumeraries were reported; 43.26% (n = 170) were located in the maxilla and 56.74% (n = 223) in the mandible. No significant differences were found between genders with respect to the total number, involvement of the dental series, or distribution of supernumerary teeth in each of the arches. CONCLUSION: Although NSMST is a condition that has a higher incidence in the male gender, no differences have been found as to their number and localization in both genders. Bilaterality seems to be a common characteristic of this disorder. PMID- 22092694 TI - Micro-marsupialization as an alternative treatment for mucocele in pediatric dentistry. AB - BACKGROUND: Mucocele is a common oral lesion in children and adolescents. Different techniques have been described for the treatment; however, all of them are invasive. AIM: This work studied the efficacy of micro-marsupialization for the treatment for mucoceles in paediatric patients. DESIGN: A retrospective review was performed using the clinical records of patients aged between 0 and 18 years with a clinical diagnosis of mucocele. The following data were obtained: age, gender, location and size of the lesion, duration of mucocele development, and type of treatment and its results. RESULTS: The mean age of the patients was 11.1 +/- 3.95 years. Mucoceles were found in the lower lip (83.7%), buccal mucosa (11.6%), and tongue (4.7%). From the overall cohort of 86 cases, 33 were treated by micro-marsupialization, of which five developed a recurrence that required surgical excision. The other 53 cases were treated by surgical excision, and three of these had recurrent disease. No statistically significant difference was found between the treatment methods. CONCLUSIONS: Micro-marsupialization can be used to treat mucoceles in paediatric dentistry. It is simpler to perform, minimally invasive, requires no local infiltration of anaesthesia, has a lower postoperative complications rate, and is well-tolerated by patients. PMID- 22092695 TI - Vertical bone augmentation with 3D-synthetic monetite blocks in the rabbit calvaria. AB - INTRODUCTION: Long-term success of osteointegrated dental implants requires sufficient volume of healthy bone at the recipient sites. However, this is frequently lacking as a result of trauma, tooth loss, or infection. Onlay autografting is amongst the most predictable techniques for craniofacial vertical bone augmentation, however, complications related to donor site morbidity are common and alternatives to onlay autografts are desirable. AIM: To develop and evaluate a new synthetic onlay block for vertical bone augmentation. MATERIAL AND METHODS: Sixteen synthetic monetite monolithic discs-shaped blocks were prepared using a 3D-printing technique. The blocks were computer-designed, and had a diameter of 9.0 mm, a thickness of either 4.0 mm (n = 8) or 3.0 mm (n = 8) and one 0.5-mm wide central hole that enabled their surgical fixation with osteosynthesis screws. The blocks were randomly allocated to each side of the calvaria (right or left) of eight New Zealand rabbits and fixed with screws to achieve vertical bone augmentation. Eight weeks after the surgical intervention, the animals were sacrificed and the calvaria were retrieved for histological analysis. The following parameters were analysed: the interaction between the graft and the original bone surface, the amount of bone ingrowth within the graft and the gain in bone height achieved by the procedure. Wilcoxon t-test was used to evaluate significant differences between the two types of monetite bone block grafts. RESULTS: The blocks were easy to handle and no damage or fracture was registered while being screw-fixated to the calvarial bone. As a result, the surgical procedure was easy and quick. After a healing of 8 weeks, the synthetic blocks were strongly fused to the calvarial bone surface. Upon histological observation, the monetite blocks appeared to be infiltrated by newly formed bone, without histological signs of necrosis, osteolysis or foreign body reaction. Histomorphometry revealed that bone augmentation occurred within and over the monetite block. The 4.0- and 3.0-mm high blocks were filled with newly formed bone with 35% and 41% of their respective volumes. These observations indicated that craniofacial bone augmentations of at least 4 mm could be achieved with synthetic monetite blocks. CONCLUSION: Within the limits of our study, this novel material may be able to eliminate the need for autologous bone transplantation for the augmentation of large vertical bone defects. PMID- 22092696 TI - Morphological and molecular characterization of Hematodinium perezi (Dinophyceae: Syndiniales), a dinoflagellate parasite of the harbour crab, Liocarcinus depurator. AB - Hematodinium perezi Chatton and Poisson 1931 (Dinophyceae: Syndiniales) is reported from one of its type hosts, Liocarcinus depurator, from Rye Bay in the English Channel, a site in a similar geographical location to that of the type description. The histology and ultrastructure of vegetative trophont stages, and rDNA sequences of the parasite infecting this host are reported for the first time. Ultrastructurally, H. perezi was confirmed by the presence of condensed chromatin profiles, trichocysts, an alveolar membrane, and micropores. The pathology of H. perezi was similar to other Hematodinium descriptions with large numbers of parasites present within the haemolymph and host tissues. No host responses against the parasite were observed. Molecular analysis of the ITS rRNA regions from H. perezi infecting L. depurator suggests that Callinectes sapidus from the United States, and Portunus trituberculatus and Scylla serrata from China are infected with different genotypes of H. perezi. The morphological and molecular characterization of H. perezi in one of the type hosts from Europe will allow for a better understanding of the phylogeny of these pathogens of commercially important Crustacea. PMID- 22092697 TI - Criteria for diagnosing pemphigus vulgaris and pemphigus foliaceus by reflectance confocal microscopy. AB - BACKGROUND: Pemphigus is an autoimmune, bullous disease affecting the skin and mucous membranes. The aim of the study was to evaluate whether pemphigus vulgaris (PV) and pemphigus foliaceus (PF), may be diagnosed using reflectance confocal microscopy (RCM). METHODS: Thirty patients (18 with PV and 12 with PF) were included into the study. In total, 36 PV lesions and 29 PF lesions were examined. Healthy-appearing skin adjacent to skin lesions and not adjacent to skin lesions was also investigated. RESULTS: Intraepidermal clefts (bullae) with acantholytic cells were observed in 47% of PV lesions and 59% of PF lesions. Multiple dilated blood vessels in the upper dermis were observed using RCM in 61% of PV lesions and in 86% of PF lesions. RCM features of pemphigus also included presence of inflammatory infiltrates, loss of typical honeycomb pattern of the epidermis, and detachment of the outer root sheath in hair follicles. In 20-64% of cases, RCM features, which are characteristic for PV and PF lesions were also observed in the proximity of these lesions within the healthy-appearing skin. Following criteria for RCM diagnosis of pemphigus were developed: (i) acantholytic clefts in RCM of a lesion, (ii) acantholytic clefts in RCM of healthy-appearing skin adjacent to a lesion, (iii) multiple-dilated blood vessels in RCM of a lesion. Fulfillment of two of these three criteria is sufficient to establish a RCM diagnosis of pemphigus. These criteria do not differentiate between PV and PF. CONCLUSIONS: RCM is useful for rapid, non-invasive, in-office differential diagnosis of pemphigus. RCM does not replace immunologic and histopathologic examinations, which remain the gold standard for establishing the final diagnosis of PV and PF. PMID- 22092698 TI - Hidradenitis suppurativa: surgical and other management techniques. AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, painful, debilitating, and emotionally distressing disease. OBJECTIVE: This article aims to provide a comprehensive review of HS, with a focus on surgical and procedural therapies for this devastating disease. MATERIALS AND METHODS: By searching PubMed using the keyword "hidradenitis suppurativa," this author identified 718 articles on this disease, among which surgical and other procedural treatments for HS represent the most common topic. This literature was reviewed. RESULTS: Management of this devastating disease comprises medical, surgical, and other procedural therapies. Medical management can be successful in controlling mild diseases, but recurrences are frequent. Surgery is considered the only curative therapy for HS. CONCLUSION: More randomized controlled trials are needed to clarify the relative efficacy of various treatment modalities; however, surgical and procedural treatments can be more successful than medical treatments, especially for patients with severe diseases. PMID- 22092699 TI - Effects of skin pressure from compression legwear on resting salivary cortisol and urinary catecholamines excretion in women. AB - BACKGROUND: The benefits of compression legwear (CL) have been demonstrated in the improvement of vascular function and venous return of the lower extremities, but their effect on autonomic nervous system (ANS) activities and human stress response remain controversial. OBJECTIVE: To investigate the possible effects of CLs on ANS activities and in inducing stress on the human body. MATERIALS AND METHODS: Resting salivary cortisol and urinary catecholamine (adrenaline and noradrenaline) excretions were examined in 12 healthy women. The effects of different skin pressure levels exerted by CL were studied by conducting a 4-hour prolonged standing and sitting wear trial with intermittent sampling of the aforementioned biochemical parameters. RESULTS: No statistically significant differences in resting salivary cortisol and urinary catecholamines were found between control and different clothing pressure conditions (light, mild, moderate, and strong), although the secretion of salivary cortisol (SSC) showed a significant decrease during the 180 minutes of the testing period that was maintained up to 10 minutes after the CL was removed for the studied pressure conditions. Urinary excretion of adrenaline and noradrenaline decreased with increasing pressure levels and was lower in response to higher clothing pressure when tested in the afternoon. CONCLUSION: Constant pressure exerted by CL did not cause any stimulation of the sympathetic nervous system. The prolonged wearing of CL while standing or sitting did not induce any stress on the human body, suggesting that CL can be safely used in the treatment of patients with venous disorders of the lower extremities. PMID- 22092700 TI - Mobilizable narrow host range plasmids as natural suicide vectors enabling horizontal gene transfer among distantly related bacterial species. AB - Klebsiella pneumoniae 287-w carries three small narrow host range (NHR) plasmids (pIGMS31, pIGMS32, and pIGRK), which could be maintained in several closely related species of Gammaproteobacteria, but not in Alphaproteobacteria. The plasmids contain different mobilization systems (MOB), whose activity in Escherichia coli was demonstrated in the presence of the helper transfer system originating from plasmid RK2. The MOBs of pIGMS31 and pIGMS32 are highly conserved in many bacterial plasmids (members of the MOB family), while the predicted MOB of pIGRK has a unique structure, encoding a protein similar to phage-related integrases. The MOBs of pIGMS31 and pIGMS32 enabled the transfer of heterologous replicons from E. coli into both gammaproteobacterial and alphaproteobacterial hosts, which suggests that these NHR plasmids contain broad host range MOB systems. Such plasmids therefore represent efficient carrier molecules, which may act as natural suicide vectors promoting the spread of diverse genetic information (including other types of mobile elements, e.g. resistance transposons) among evolutionarily distinct bacterial species. Thus, mobilizable NHR plasmids may play a much more important role in horizontal gene transfer than previously thought. PMID- 22092701 TI - Assimilatory nitrate utilization by bacteria on the West Florida Shelf as determined by stable isotope probing and functional microarray analysis. AB - Dissolved inorganic nitrogen (DIN) uptake by marine heterotrophic bacteria has important implications for the global nitrogen (N) and carbon (C) cycles. Bacterial nitrate utilization is more prevalent in the marine environment than traditionally thought, but the taxonomic identity of bacteria that utilize nitrate is difficult to determine using traditional methodologies. (15) N-based DNA stable isotope probing was applied to document direct use of nitrate by heterotrophic bacteria on the West Florida Shelf. Seawater was incubated in the presence of 2 MUM (15) N ammonium or (15) N nitrate. DNA was extracted, fractionated via CsCl ultracentrifugation, and each fraction was analyzed by terminal restriction fragment length polymorphism (TRFLP) analysis. TRFs that exhibited density shifts when compared to controls that had not received (15) N amendments were identified by comparison with 16S rRNA gene sequence libraries. Relevant marine proteobacterial lineages, notably Thalassobacter and Alteromonadales, displayed evidence of (15) N incorporation. RT-PCR and functional gene microarray analysis could not demonstrate the expression of the assimilatory nitrate reductase gene, nasA, but mRNA for dissimilatory pathways, i.e. nirS, nirK, narG, nosZ, napA, and nrfA was detected. These data directly implicate several bacterial populations in nitrate uptake, but suggest a more complex pattern for N flow than traditionally implied. PMID- 22092702 TI - High frequency of glucose-utilizing mutants in Shewanella oneidensis MR-1. AB - Shewanella oneidensis MR-1 has conventionally been considered unable to use glucose as a carbon substrate for growth. The genome sequence of S. oneidensis MR 1 however suggests the ability to use glucose. Here, we demonstrate that during initial glucose exposure, S. oneidensis MR-1 quickly and frequently gains the ability to utilize glucose as a sole carbon source, in contrast to wild-type S. oneidensis, which cannot immediately use glucose as a sole carbon substrate. High performance liquid chromatography and (14)C glucose tracer studies confirm the disappearance in cultures and assimilation and respiration, respectively, of glucose. The relatively short time frame with which S. oneidensis MR-1 gained the ability to use glucose raises interesting ecological implications. PMID- 22092703 TI - Evidence for an exercise induced increase of TNF-alpha and IL-6 in marathon runners. AB - Regular physical activity of moderate intensity improves cardiovascular risk factors including low-grade inflammation. However, acute vigorous exercise such as marathon running results in marked increases of circulating pro-inflammatory markers. Up to now, the origin of this pro-inflammatory boost is still debated equivocally. We analyzed the change of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and leptin from pre- to immediately post-race in 15 male runners (age 43 +/- 10.9 years and body mass index 24.5 +/- 2.7 kg/m(2) ) both on the protein level in the plasma and on the messenger ribonucleic acid (mRNA) level in blood mononuclear cells (BMNC). We observed a significant increase of IL-6 (prerace 2.08 +/- 0.10 ng/L and postrace 40.14 +/- 24.85 ng/L, P < 0.001) and TNF-alpha (prerace 8.14 +/- 1.38 ng/L and postrace 12.40 +/- 3.15 ng/L, P < 0.001) and a decrease of leptin (prerace 1.64 +/- 2.64 MUg/L and postrace 0.80 +/- 1.70 MUg/L, P = 0.04) serum levels after the marathon race. Furthermore, TNF-alpha, IL-6, and leptin were expressed (mRNA level) in BMNC. However no significant differences in mRNA levels were seen before and after the run in these cells. We found an up-regulation of TNF-alpha and IL-6 in the plasma during vigorous exercise. This increase is not attributable to BMNC. We assume a local production in, or release from, exercised tissues. PMID- 22092704 TI - Reference intervals for Greyhounds and Lurchers using the Sysmex XT-2000iV hematology analyzer. AB - BACKGROUND: The need for breed-specific reference intervals (RIs) for Greyhounds has been identified. As Lurchers are a sighthound cross-breed, specific RIs may also be needed for these dogs. Hematologic RIs for Greyhounds and Lurchers using the Sysmex XT-2000iV hematology analyzer have not been established. OBJECTIVES: The aims of this study were to establish RIs for Greyhounds using the Sysmex XT 2000iV, to investigate whether RIs for Greyhound and nonsighthound dogs could be transferred to Lurchers, and to establish new RIs for Lurchers if transference was not possible. METHODS: Data were retrieved retrospectively from a database of blood donor dogs. Greyhound RIs were established using nonparametric methods based on a reference population of 179 dogs. For the RI transference study, 38 Lurchers were selected, following guidelines proposed by the Clinical and Laboratory Standards Institute. When transference was not appropriate, new RIs were generated using the robust method. RESULTS: Greyhound RIs for the Sysmex hematology analyzer reflected known differences in this breed with a tendency toward higher RBC mass and lower WBC and platelet counts. RIs for hemoglobin concentration, HCT, MCV, MCH, MCHC, and WBC, neutrophil, lymphocyte, monocyte, and platelet counts for Greyhounds were suitable for transference to Lurchers. For RBC and eosinophil counts, new RIs were established. CONCLUSION: Our study suggests that Lurchers share many hematologic characteristics with Greyhounds, but had higher reference limits for RBC and eosinophil counts. PMID- 22092705 TI - Analysis of the influence of residual alveolar bone height on sinus augmentation outcomes. AB - INTRODUCTION: Maxillary sinus augmentation is a predictable implant site development technique for posterior atrophic maxillary ridges. However, graft consolidation requires adequate angiogenesis and migration of osteogenic cells from native bone. Therefore, the amount of residual bone height (RBH) may play a role in the rate of graft maturation. The purpose of this study was to analyze the influence of RBH in the histomorphometric outcomes of maxillary sinus augmentation procedures. MATERIAL AND METHODS: Patients in need of sinus augmentation were recruited for the study. Customized radiographic guides were fabricated and a cone-beam computerized tomography scan was obtained at baseline. Two examiners measured RBH on the scans at the locations marked by the radiographic guide. Sinus grafting was performed by a lateral window approach using a particulated mineralized allograft. Patients were followed up for 6 months. At the time of implant placement, bone core biopsies were harvested using the radiographic guide, which was converted into a surgical guide. Samples were histomorphometrically analyzed. Proportion of vital bone (%VB), remaining allograft particles (%RA), and non-mineralized tissue (%NMT) were quantified. Categorical analysis of correlation of RBH (<4 or >=4 mm) with%VB and%RA was performed using a statistical model. RESULTS: Twenty-one patients underwent sinus augmentation for a total of 21 sinuses. One patient developed an infection after grafting and was excluded. Histomorphometric analysis revealed that mean%VB was 20.47 +/- 18.25, mean %RA was 29.04 +/- 24.94, and average %NMT was 50.47 +/- 12.76. No significant correlation between RBH and %VB (r = 0.016; P = 0.951), and RBH and % (r = 0.009; P = 0.971) was found. Similarly, categorical analysis of correlation showed no statistical significance. CONCLUSION: These findings suggest that the remaining alveolar bone height does not appear to influence the maturation and consolidation of an allograft in the maxillary sinus. PMID- 22092706 TI - Abiotic heterogeneity drives parasite local adaptation in coevolving bacteria and phages. AB - Spatial abiotic heterogeneity can result in divergent selection, hence might increase the magnitude of host-parasite local adaptation (the mean difference in fitness of sympatric vs. allopatric host-parasite combinations). We explicitly tested this hypothesis by measuring local adaptation in experimentally coevolved populations of bacteria and viruses evolved in the same or different nutrient media. Consistent with previous work, we found that mean levels of evolved phage infectivity and bacteria resistance varied with nutrient concentration, with maximal levels at nutrient concentrations that supported the greatest densities of bacteria. Despite this variation in evolved mean infectivity and resistance between treatments, we found that parasite local adaptation was greatly increased when measured between populations evolved in different, compared with the same, media. This pattern is likely to have resulted from different media imposing divergent selection on bacterial hosts, and phages in turn adapting to their local hosts. These results demonstrate that the abiotic environment can play a strong and predictable role in driving patterns of local adaptation. PMID- 22092707 TI - Seasonal patterns in the sunlight sensitivity of bacterioplankton from Mediterranean surface coastal waters. AB - The sensitivity of coastal marine bacterioplankton to natural photosynthetically active radiation (PAR, 400-700 nm) and ultraviolet radiation (UVR, 280-400 nm) was evaluated in five experiments over a seasonal cycle in the Blanes Bay, NW Mediterranean Sea. Exposure to natural solar radiation generally inhibited bulk bacterial activities or damaged membrane integrity when irradiances were high (i.e. spring and summer experiments) and, in general, UVB (280-320 nm) accounted for most of the inhibition. When assessing activity ((3) H-leucine uptake) at the single-cell level by microautoradiography and rRNA gene probing, seasonally varying responses and sensitivities were found among bacterial groups. While autumn and winter irradiances seemed too low to cause changes in activity, variable effects were found in spring and summer. SAR11 was consistently inhibited by UVR and PAR exposure, whereas Gammaproteobacteria and Bacteroidetes showed higher resistance. Roseobacter, Synechococcus and the NOR5 clade were occasionally photostimulated in their activity, mainly because of PAR. Our results indicate that a component of seasonality exists in the bacterial responses to solar radiation, which vary not only depending on the irradiance and the spectral characteristics, but also on the previous light history and the taxonomic composition of the community. PMID- 22092708 TI - The copper responding surfaceome of Methylococccus capsulatus Bath. AB - Proteins on the cellular surface of a bacterium, its surfaceome, are part of the interface between the bacterium and its environment, and are essential for the cells response to its habitat. Methylococcus capsulatus Bath is one of the most extensively studied methane-oxidizers and is considered as a model-methanotroph. The composition of proteins of the surfaceome of M. capsulatus Bath varies with the availability of copper and changes significantly upon only minor changes of copper concentration in the sub-MUM concentration range. Proteins that respond to the changes in copper availability include the assumed copper acquisition protein MopE, c-type heme proteins (SACCP, cytochrome c(553o) proteins) and several proteins of unknown function. The most intriguing observation is that multi-heme c-type cytochromes are major constituents of the M. capsulatus Bath surfaceome. This is not commonly observed in bacteria, but is a feature shared with the dissimilatory metal-reducing bacteria. Their presence on the M. capsulatus Bath cellular surface may be linked to the cells ability to efficiently adapt to changing growth conditions and environmental challenges. However, their possible role(s) in methane oxidation, nitrogen metabolism, copper acquisition, redox reactions and/or electron transport remain(s) at present an open question. This review will discuss the possible significance of these findings. PMID- 22092709 TI - The chemotaxis-like Che1 pathway has an indirect role in adhesive cell properties of Azospirillum brasilense. AB - The Azospirillum brasilense chemotaxis-like Che1 signal transduction pathway was recently shown to modulate changes in adhesive cell surface properties that, in turn, affect cell-to-cell aggregation and flocculation behaviors rather than flagellar-mediated chemotaxis. Attachment to surfaces and root colonization may be functions related to flocculation. Here, the conditions under which A. brasilense wild-type Sp7 and che1 mutant strains attach to abiotic and biotic surfaces were examined using in vitro attachment and biofilm assays combined with atomic force microscopy and confocal microscopy. The nitrogen source available for growth is found to be a major modulator of surface attachment by A. brasilense and could be promoted in vitro by lectins, suggesting that it depends on interaction with surface-exposed residues within the extracellular matrix of cells. However, Che1-dependent signaling is shown to contribute indirectly to surface attachment, indicating that distinct mechanisms are likely underlying flocculation and attachment to surfaces in A. brasilense. PMID- 22092710 TI - The rhamnolipid stress response of Bacillus subtilis. AB - Rhamnolipids are biosurfactants produced by the soil bacterium P seudomonas aeruginosa. In addition to their high industrial potential as surface-active molecules, rhamnolipids also have antimicrobial properties. In densely populated habitats, such as the soil, production of antimicrobial compounds is important to inhibit growth of competitors. For the latter, it is crucial for survival to sense and respond to the presence of those antibiotics. To gain a first insight into the biological competition involving biosurfactants, we investigated the cellular response of the model organism B acillus subtilis upon exposure to rhamnolipids by genome-wide transcriptional profiling. Most of the differentially expressed genes can be assigned to two different regulatory networks: the cell envelope stress response mediated by the two-component system LiaRS and the extracytoplasmic function sigma factor sigma(M) and the CssRS-dependent secretion stress response. Subsequent phenotypic analysis demonstrated a protective function of LiaRS and sigma(M) against cell lysis caused by rhamnolipids. Taken together, we present the first evidence that a single antimicrobial compound can simultaneously induce genes from two independent stress stimulons. PMID- 22092711 TI - Ploidy in cyanobacteria. AB - A recently developed real-time PCR method for the determination of genome copy numbers was optimized for the application to cyanobacteria. Three species were chosen to represent a fresh water species, a salt water species, and two strains of a widely used laboratory species. Synechococcus PCC 7942 and Synechococcus WH7803 were found to contain 3-4 genome copies per cell and are thus oligoploid, confirming earlier publications. In contrast, Synechocystis PCC 6803 is highly polyploid. The motile wild-type strain contains 218 genome copies in exponential phase and 58 genome copies in linear and in stationary growth phase. The GT wild type strain contains 142 genome copies in exponential phase and 42 genome copies in linear and stationary growth phase. These are the highest numbers found for any cyanobacterial species. Notably these values are much higher than the value of 12 genome copies published for the 'Kazusa' strain more than 20 years ago. The results reveal that for Synechocystis PCC 6803 strain differences exist and that the ploidy level is highly growth phase-regulated. A compilation of the ploidy levels of all investigated cyanobacterial species gives an overview of the genome copy number distribution and shows that monoploid, oligoploid, and polyploid cyanobacteria exist. PMID- 22092712 TI - Subcellular localization of N-deoxyribosyltransferase in Lactobacillus fermentum: cell surface association of an intracellular nucleotide metabolic enzyme. AB - N-deoxyribosyltransferases are essential enzymes in the nucleotide salvage pathway of lactobacilli. They catalyze the exchange between the purine or pyrimidine bases of 2'-deoxyribonucleosides and free pyrimidine or purine bases. In general, N-deoxyribosyltransferases are referred to as cytoplasmic enzymes, although there is no experimental evidence for this subcellular localization. In this work, the subcellular localization of N-deoxyribosyltransferase II (NTD) from Lactobacillus fermentum was examined by subcellular fractionation, transmission electron microscopy, and fluorescence microscopy. Our results indicate that L. fermentum NTD are distributed not only in the cytoplasm but also on the cell wall surface, and further studies showed that surface-attached NTD can be released into the culture broth and conventional buffers. PMID- 22092713 TI - Quantitative proteomics of Chlorobaculum tepidum: insights into the sulfur metabolism of a phototrophic green sulfur bacterium. AB - Chlorobaculum (Cba.) tepidum is a green sulfur bacterium that oxidizes sulfide, elemental sulfur, and thiosulfate for photosynthetic growth. To gain insight into the sulfur metabolism, the proteome of Cba. tepidum cells sampled under different growth conditions has been quantified using a rapid gel-free, filter-aided sample preparation (FASP) protocol with an in-solution isotopic labeling strategy. Among the 2245 proteins predicted from the Cba. tepidum genome, approximately 970 proteins were detected in unlabeled samples, whereas approximately 630-640 proteins were detected in labeled samples comparing two different growth conditions. Wild-type cells growing on thiosulfate had an increased abundance of periplasmic cytochrome c-555 and proteins of the periplasmic thiosulfate oxidizing SOX enzyme system when compared with cells growing on sulfide. A dsrM mutant of Cba. tepidum, which lacks the dissimilatory sulfite reductase DsrM protein and therefore is unable to oxidize sulfur globules to sulfite, was also investigated. When compared with wild type, the dsrM cells exhibited an increased abundance of DSR enzymes involved in the initial steps of sulfur globule oxidation (DsrABCL) and a decreased abundance of enzymes putatively involved in sulfite oxidation (Sat-AprAB-QmoABC). The results show that Cba. tepidum regulates the cellular levels of enzymes involved in sulfur metabolism and other electron-transferring processes in response to the availability of reduced sulfur compounds. PMID- 22092714 TI - High-resolution melting for analysis of short sequence repeats in Mycobacterium avium subsp. paratuberculosis. AB - Analysis of micro- and minisatellite loci is widely used in sub-typing of Mycobacterium avium subsp. paratuberculosis. Microsatellite (short sequence repeat, SSR) loci have shown highest discriminatory power, but direct sequencing of amplicons is required for correct assignment of the repeat number. We developed an alternative method to sequencing, focusing on the SSR8 locus (constituted by GGT triplets from three to six repeats). The approach is based on asymmetric quantitative PCR, followed by high-resolution melting analysis with unlabelled probes (UP-HRM). Data showed perfect concordance between direct sequencing and UP-HRM, which is faster, simpler and more cost effective. PMID- 22092715 TI - Helicobacter pylori CagA-mediated IL-8 induction in gastric epithelial cells is cholesterol-dependent and requires the C-terminal tyrosine phosphorylation containing domain. AB - Upon infection of the gastric epithelial cells, the Helicobacter pylori cytotoxin associated gene A (CagA) virulence protein is injected into the epithelial cells via the type IV secretion system (TFSS), which is dependent on cholesterol. Translocated CagA is targeted by the membrane-recruited c-Src family kinases in which a tyrosine residue in the Glu-Pro-Ile-Tyr-Ala (EPIYA)-repeat region, which can be phosphorylated, induces cellular responses, including interleukin-8 (IL-8) secretion and hummingbird phenotype formation. In this study, we explored the role of EPIYA-containing C-terminal domain (CTD) in CagA tethering to the membrane lipid rafts and in IL-8 activity. We found that disruption of the lipid rafts reduced the level of CagA translocation/phosphorylation as well as CagA mediated IL-8 secretion. By CagA truncated mutagenesis, we identified that the CTD, rather than the N-terminal domain, was responsible for CagA tethering to the plasma membrane and association with detergent-resistant membranes, leading to CagA-induced IL-8 promoter activity. Our results suggest that CagA CTD-containing EPIYAs directly interact with cholesterol-rich microdomains that induce efficient IL-8 secretion in the epithelial cells. PMID- 22092716 TI - Streptococcus sanguinis induces foam cell formation and cell death of macrophages in association with production of reactive oxygen species. AB - Streptococcus sanguinis, a normal inhabitant of the human oral cavity, is a common streptococcal species implicated in infective endocarditis. Herein, we investigated the effects of infection with S. sanguinis on foam cell formation and cell death of macrophages. Infection with S. sanguinis stimulated foam cell formation of THP-1, a human macrophage cell line. At a multiplicity of infection >100, S. sanguinis-induced cell death of the macrophages. Viable bacterial infection was required to trigger cell death because heat-inactivated S. sanguinis did not induce cell death. The production of cytokines interleukin 1beta and tumor necrosis factor-alpha from macrophages was also stimulated during bacterial infection. Inhibition of the production of reactive oxygen species (ROS) resulted in reduced cell death, suggesting an association of ROS with cell death. Furthermore, S. sanguinis-induced cell death appeared to be independent of activation of inflammasomes, because cleavage of procaspase-1 was not evident in infected macrophages. PMID- 22092717 TI - Listeria monocytogenes adapts to long-term stationary phase survival without compromising bacterial virulence. AB - Bacteria withstand starvation during long-term stationary phase through the acquisition of mutations that increase bacterial fitness. The evolution of the growth advantage in stationary phase (GASP) phenotype results in the ability of bacteria from an aged culture to outcompete bacteria from a younger culture when the two are mixed together. The GASP phenotype was first described for Escherichia coli, but has not been examined for an environmental bacterial pathogen, which must balance long-term survival strategies that promote fitness in the outside environment with those that promote fitness within the host. Listeria monocytogenes is an environmental bacterium that lives as a saprophyte in soil, but is capable of replicating within the cytosol of mammalian cells. Herein, we demonstrate the ability of L. monocytogenes to express GASP via the acquisition of mutations during long-term stationary growth. Listeria monocytogenes GASP occurred through mechanisms that were both dependent and independent of the stress-responsive alternative sigma factor SigB. Constitutive activation of the central virulence transcriptional regulator PrfA interfered with the development of GASP; however, L. monocytogenes GASP cultures retained full virulence in mice. These results indicate that L. monocytogenes can accrue mutations that optimize fitness during long-term stationary growth without negatively impacting virulence. PMID- 22092718 TI - Effect of interactions between Mip and PrtA on the full extracellular protease activity of Xanthomonas campestris pathovar campestris. AB - Mip (macrophage infectivity potentiator) and Mip-like proteins have been demonstrated to be involved in virulence of several animal pathogens, but as yet none of their native bacterial targets has been identified. Our previous work demonstrated that the Mip-like protein found in the plant pathogen Xanthomonas campestris pv. campestris (Xcc) (hereafter called Mip(Xcc)) is also involved in virulence. Inactivation of the mip(Xcc) gene leads to a significant reduction in exopolysaccharide production and extracellular protease activity via an unknown mechanism. The Xcc genome encodes six extracellular proteases, all of which are secreted via the type II secretion system. The serine protease PrtA makes the largest contribution to Xcc's total extracellular proteolytic activity. In this study, Western blotting analysis demonstrated that Mip(Xcc) was located in the periplasm. Bacterial two-hybrid and far-Western analysis indicated that Mip(Xcc) interacted with PrtA directly. Purified Mip(Xcc) was found to be able to rescue the protease activity of periplasmic proteins extracted from the mip(Xcc) mutant. These findings show that Mip(Xcc) plays a role in the maturation of PrtA, which is the novel native target for at least one Mip or Mip-like protein. PMID- 22092719 TI - Effect of substrate type on bacterial community composition in biofilms from the Great Barrier Reef. AB - Natural and anthropogenic impacts such as terrestrial runoff, influence the water quality along the coast of the Great Barrier Reef (GBR) and may in turn affect coral reef communities. Associated bacterial biofilms respond rapidly to environmental conditions and are potential bioindicators for changes in water quality. As a prerequisite to study the effects of water quality on biofilm communities, appropriate biofilm substrates for deployment in the field must be developed and evaluated. This study investigates the effect of different settlement substrates (i.e. glass slides, ceramic tiles, coral skeletons and reef sediments) on bacterial biofilm communities grown in situ for 48 days at two locations in the Whitsunday Island Group (Central GBR) during two sampling times. Bacterial communities associated with the biofilms were analysed using terminal restriction fragment length polymorphism (T-RFLP) and clone library analyses of 16S rRNA genes. Findings revealed that substrate type had little influence on bacterial community composition. Of particular relevance, glass slides and coral skeletons exhibited very similar communities during both sampling times, suggesting the suitability of standardized glass slides for long-term biofilm indicator studies in tropical coral reef ecosystems. PMID- 22092720 TI - Isolation of the fenoxaprop-ethyl (FE)-degrading bacterium Rhodococcus sp. T1, and cloning of FE hydrolase gene feh. AB - An enrichment culture which completely degraded fenoxaprop-ethyl (FE) was acquired by using FE as sole carbon source. An efficient FE-degrading strain T1 was isolated from the enrichment culture and identified as Rhodococcus sp. Strain T1 could degrade 94% of 100 mg L(-1) FE within 24 h and the metabolite fenoxaprop acid (FA) was identified by HPLC/MS analysis. This strain converted FE by cleavage of the ester bond, but could not further degrade FA. Strain T1 could also efficiently degrade haloxyfop-R-methyl, quizalofop-p-ethyl, cyhalofop-butyl and clodinafop-propargyl. FE hydrolase capable of hydrolysing FE to FA was found in the cell-free extract of strain T1 by zymogram analysis. A novel gene feh encoding FE hydrolase was cloned by shotgun library construction and successfully expressed in Escherichia coli. PMID- 22092721 TI - A neuro-endocrine-immune symphony. AB - The inflammatory response provides a powerful means for the body to fight an infection. The neuroendocrine system plays an important role in controlling the magnitude and duration of this response and maintaining homeostasis in the inflamed state. Glucocorticoids released following activation of the hypothalamic pituitary-adrenal axis limit the synthesis of pro-inflammatory molecules, whereas the neurohypophysial hormones vasopressin and oxytocin act both within the brain and in the periphery to maintain cardiovascular and metabolic homeostasis and to limit the rise in body temperature. PMID- 22092722 TI - Assessment of melanocytic skin lesions with a high-definition laser Doppler imaging system. AB - BACKGROUND: Early detection is a major goal in the management of malignant melanoma. Besides clinical assessment many noninvasive technologies such as dermoscopy, digital dermoscopy and in vivo laser scanner microscopy are used as additional methods. Herein we tested a system to assess lesional perfusion as a tool for early melanoma detection. METHODS: Laser Doppler flow (FluxExplorer) and mole analyser (MA) score (FotoFinder) were applied to histologically verified melanocytic nevi (33) and malignant melanomas (12). RESULTS: Mean perfusion and MA scores were significantly increased in melanoma compared to nevi. However, applying an empirically determined threshold of 16% perfusion increase only 42% of the melanomas fulfilled the criterion of malignancy, whereas with the mole analyzer score 82% of the melanomas fulfilled the criterion of malignancy. CONCLUSION: Laser Doppler imaging is a highly sensitive technology to assess skin and skin tumor perfusion in vivo. Although mean perfusion is higher in melanomas compared to nevi the high numbers of false negative results hamper the use of this technology for early melanoma detection. PMID- 22092723 TI - An analysis of the decision-making process for single implant treatment in general practice. AB - PURPOSE: To study the frequency of and factors associated with the decision to perform single implant treatment after tooth extraction by general practitioners in a private, fee-for-service setting. MATERIAL AND METHODS: One hundred practitioners with a general dental practice in Ghent were randomly selected. Clinicians were asked to fill in a study form for every single extraction they performed during an 8-week period. The form related to the treatment decision and a number of patient- and clinician-related factors. RESULTS: Ninety-four general dentists (52 men, 42 women; mean age 49; range 24-68) agreed to participate and extracted 1180 single teeth. After exclusion of third molars and cases where the reason for tooth loss would generally prohibit replacement, 900 cases were identified. In 24% of these patients, there was no treatment decision and in 18% replacement was deemed unnecessary. When replacement was necessary (n = 526), removable partial denture (RPD), fixed partial denture (FPD), single implant treatment and resin-bonded bridge were chosen in 54%, 24%, 21% and 1% of the patients, respectively. Multinomial logistic regression was used to evaluate the decision-making process for single implant treatment against RPD and FPD. In relation to RPD, single implant treatment was more likely in highly educated patients with few missing teeth and no bone loss at adjacent teeth. In relation to FPD, single implant treatment was more likely in patients with intact adjacent teeth and when the tooth was extracted by a female dentist. Experience in implant prosthetics was positively associated with single implant treatment in all analyses. CONCLUSIONS: Single implant treatment is not the most common procedure in daily practice to restore a single tooth gap. Patient's education, oral factors and clinician-related factors may affect the decision-making process, whereas medical factors may not. PMID- 22092724 TI - Predictive value of ridge dimensions on autologous bone graft resorption in staged maxillary sinus augmentation surgery using Cone-Beam CT. AB - INTRODUCTION: No studies are available that provide predictive parameters regarding the expected amount of resorption after maxillary sinus augmentation surgery using autologous bone grafts. Therefore, the aim of this study was to determine parameters influencing the outcome of the bone graft resorption process. MATERIAL AND METHODS: In 20 patients, three-dimensional analysis of alveolar ridge dimensions and bone graft volume change in the atrophic posterior maxilla was performed by Cone-Beam Computerized Tomography imaging. Ridge dimensions were assessed before maxillary sinus augmentation surgery. Bone graft volumes were compared after maxillary sinus floor augmentation surgery and a graft healing interval of several months. To analyze the relation between bone volume changes with the independent variables, patients' gender, age, alveolar crest height and width, and graft healing time interval, a multi-level extension of linear regression was applied. RESULTS: A residual bone height of 6.0 mm (SD = 3.6 mm) and 6.2 mm (SD = 3.6 mm) was found at the left and right sides, respectively. Moreover, alveolar bone widths of 6.5 mm (SD = 2.2 mm) and 7.0 mm (SD = 2.3 mm) at the premolars, and 8.8 mm (SD = 2.2 mm) and 8.9 mm (SD = 2.5 mm) at the molars regions were found at the left and right site, respectively. Bone graft volume decreased by 25.0% (SD = 21.0%) after 4.7 months (SD = 2.7, median = 4.0 months) of healing time. The variables "age" (P = 0.009) and mean alveolar crest "bone height" (P = 0.043), showed a significant influence on bone graft resorption. A decrease of 1.0% (SE = 0.3%) of bone graft resorption was found for each year the patient grew older, and an increase in bone graft resorption of 1.8% (SE = 0.8%) was found for each mm of original bone height before sinus floor augmentation. CONCLUSIONS: Graft resorption occurs when using autologous bone grafts for maxillary sinus augmentation. Alveolar crest bone height and patient age have a significant effect on graft resorption, with increased resorption for higher alveolar crest bone height and decreased resorption for older patients. Consequently, patient characteristics that affect the process of bone graft resorption should be given full consideration, when performing sinus augmentation surgery. PMID- 22092725 TI - Quality of care for cardiovascular disease and diabetes amongst individuals with serious mental illness and those using antipsychotic medications. AB - Individuals living with serious mental illness (SMI) experience excess mortality due to natural causes. Cardiovascular disease (CVD) and diabetes are twice as prevalent in SMI populations as in the general population, and this may be partly related to unhealthy lifestyle behaviors and the use of antipsychotic medications. This review examined comparative studies of quality of care in SMI and non-SMI populations, and studies investigating cardio-metabolic screening in patients prescribed antipsychotics. We identified that individuals with SMI are around 30% less likely than those without SMI to receive hospital care for CVD and diabetes complications, to receive blood glucose, lipid, and other diabetes tests, to undergo invasive procedures, and to be prescribed medications known to be effective in the treatment of CVD and diabetes. In addition, less than 30% of individuals with SMI may receive examinations for weight, blood glucose, and lipids, before or during treatment with antipsychotics. Evidence from studies within the U.S.' Veteran Affairs health care system indicates that the integration of physical and mental health services may be beneficial in reducing disparities in health care for individuals with SMI. Clear policies, which identify practitioner responsibilities for cardio-metabolic screening in patients receiving antipsychotic therapy must be disseminated. PMID- 22092726 TI - Biological complications and peri-implant clinical and radiographic changes at immediately placed dental implants. A prospective 5-year cohort study. AB - OBJECTIVES: To evaluate clinically and radiographically immediate implants 5 years after insertion and to compare them with delayed-placed implants in the same subjects. MATERIAL AND METHODS: Twenty-two consecutive patients that needed at least two implants for replacing hopeless teeth, one immediately upon extraction and the other in a delayed fashion (at least 4 months post-extraction) were selected in this prospective cohort study. Post-extraction immediate implants (II) and delayed implants (DI) groups were defined. One and 5 years after implant loading, clinical and radiographical outcome variables were recorded and analysed both at site and at implant level. Intra-group and inter group comparisons were performed. RESULTS: The intergroup comparison did not show significant differences for plaque index, bleeding on probing and suppuration. These parameters worsen in both groups along the study. This trend was stronger for the plaque index in the group II, which increased from 15.6% at 1 year to 25.9% at 5 years (P < 0.04). One year after loading, the sites with probing depth >=5 mm were higher for the group II compared to DI (2.5% vs. 0%; P = 0.049). At the end of the study, no significant statistical differences were found. Radiographically, bone crestal changes did not yield significant differences. During the follow-up period, 25% of the implants (26.4% in group II and 23.5% in DI) showed biological complications: mucositis (20%) and/or periimplantitis (5.8%). No differences between groups were found. CONCLUSIONS: Within the same patients, the implants placed with the immediate protocol demonstrated a higher tendency to crestal bone loss and to peri-implantitis, although these differences were not statistically significant. PMID- 22092727 TI - Fractionated 1550-nm erbium-doped fiber laser for the treatment of periorbital hyperpigmentation. PMID- 22092730 TI - Continuous ultra-low-intensity artificial daylight is not as effective as red LED light in photodynamic therapy of multiple actinic keratoses. AB - BACKGROUND/PURPOSE: Daylight-mediated photodynamic therapy (PDT) is a simple and tolerable treatment of nonmelanoma skin cancer. It is of interest which light intensity is sufficient to prevent accumulation of protoporphyrin IX (PpIX) and effectively treat actinic keratoses (AKs). We compared the efficacy of PDT with light-emitting diode (LED) to daylight-mediated PDT with very low-intensity artificial daylight ('daylight') in the treatment of multiple AKs in the face or scalp. METHODS: Twenty patients were treated with conventional methyl aminolevulinate (MAL) PDT in one area. Another area was, after half an hour of occlusive treatment with MAL, illuminated for 2.5 h with low-intensity 'daylight' (0.5 mW/cm(2) -3.7 mW/cm(2)) that corresponds to midday outdoor intensity in the Scandinavian winter. RESULTS: After 3 months, with a response rate of 52%, low dose artificial daylight was less effective than conventional LED-PDT (63%) (P = 0.0017). The mean PpIX light dose during 'daylight' exposure was 2.23 J/cm(2) and the lower the PpIX light intensity, the higher the accumulation of PpIX (P = 0.003). CONCLUSIONS: Even very low-intensity/dose artificial daylight-mediated PDT of multiple AKs resulted in a response rate of more than 50%. However, to ensure efficacies equivalent to conventional LED-PDT, the treatment should not be conducted on very overcast days. PMID- 22092728 TI - Nitric oxide and related enzymes in asthma: relation to severity, enzyme function and inflammation. AB - BACKGROUND: Exhaled nitric oxide (FeNO) associates with asthma and eosinophilic inflammation. However, relationships between nitric oxide synthases, arginase, FeNO, asthma severity and inflammation remain poorly understood. OBJECTIVES: To determine the relationships of iNOS expression/activation and arginase 2 expression with asthma severity, FeNO, nitrotyrosine (NT) and eosinophilic inflammation. METHODS: Bronchial brushings and sputum were obtained from 25 normal controls, eight mild/no inhaled corticosteroids (ICS), 16 mild moderate/with ICS and 35 severe asthmatics. The FeNO was measured the same day by ATS/ERS standards. The iNOS, arginase2 mRNA/protein and NT protein were measured in lysates from bronchial brushings by quantitative real-time PCR and Western blot. Induced sputum differentials were obtained. RESULTS: Severe asthma was associated with the highest levels of iNOS protein and mRNA, although the index of iNOS mRNA to arginase2 mRNA most strongly differentiated severe from milder asthma. When evaluating NO-related enzyme functionality, iNOS mRNA/protein expression both strongly predicted FeNO (r = 0.61, P < 0.0001 for both). Only iNOS protein predicted NT levels (r = 0.48, P = 0.003) with the strongest relationship in severe asthma (r = 0.61, P = 0.009). The iNOS protein, FeNO and NT, all correlated with sputum eosinophils, but the relationships were again strongest in severe asthma. Controlling for arginase 2 mRNA/protein did not impact any functional outcome. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that while iNOS expression from epithelial brushings is highest in severe asthma, factors controlling arginase2 mRNA expression significantly improve differentiation of severity. In contrast, functionality of the NO pathway as measured by FeNO, NT and eosinophilic inflammation, is strongly associated with iNOS expression alone, particularly in severe asthma. PMID- 22092731 TI - Compliance with age and skin type restrictions following the introduction of indoor tanning legislation in Melbourne, Australia. AB - BACKGROUND/PURPOSE: The study aimed to establish compliance of indoor tanning businesses with 2009 legislation, particularly with requirements to provide information on skin cancer and exclude people under 18 or with fair skin. METHODS: Compliance was tested through surveys and in-person visits to 30 businesses in Melbourne, Australia. Research assistants presented as potential customers with different profiles: young adults eligible to use a sunbed, young adults with fair skin, under age customers who prompted with their age and under age customers who concealed their age and claimed to be 18 if asked. RESULTS: Communicating the risks of skin cancer during the visit improved from 70% in 2003, prior to the introduction of legislation, to 97% in 2009. While there were improvements in restricting access to sunbeds among high-risk groups, compliance of indoor tanning businesses with age and skin type restrictions remained less than optimal. Almost half (47%) allowed access to fair-skinned research assistants, compared with 90% in 2003. Only one of the 30 operators allowed access to a teenager who prompted with her age; in 2003, 52% of under age teenagers were granted access without parental consent. However, when teenagers concealed their age or claimed to be 18, 80% of operators granted them access. CONCLUSIONS: The findings suggest that regulation of the indoor tanning industry is a better approach to this health issue than voluntary standards and/or education. Nonetheless, inadequate compliance with requirements to exclude high risk groups lends weight to calls for stricter monitoring and enforcement, or an absolute ban. PMID- 22092732 TI - Comparison of topical 8-methoxypsoralen and narrowband ultraviolet B with narrowband ultraviolet B alone in treatment-resistant sites in plaque-type psoriasis: a placebo-controlled study. AB - BACKGROUND: Combination of topical methoxsalen and narrowband ultraviolet B (NBUVB) was shown to be more effective than NBUVB alone in treating plaque-type psoriasis. OBJECTIVE: To find out whether topical methoxsalen and NBUVB had any benefit in induction of remission on treatment-resistant plaques of psoriasis on the legs in comparison with NBUVB alone. METHODS: Ten patients were included. Two symmetric lesions with similar Psoriasis Severity Index score on the lower legs were randomly assigned to be treated with cold cream as placebo or 0.1% 8 methoxypsoralen (8MOP) cream 15 min before phototherapy with NBUVB. Phototherapy was given three times per week for up to three months. Severity scores were recorded each week and side effects were observed before each session. RESULTS: Significant decrease in the severity score was observed in both groups (P-value < 0.001), but none of the lesions cleared completely at the end of the study. The decrease of the score in the 8MOP arm was greater than the control arm; however, the difference was not significant. The only side effect was pigmentation that occurred in all of the 8MOP-treated patients after 2 weeks. CONCLUSION: We could not confirm any significant benefit of topical methoxsalen and NBUVB in comparison to NBUVB alone in treating resistant plaques of psoriasis on the legs. PMID- 22092733 TI - Effects of ultraviolet radiation exposure on FOXP3+ infiltration in cutaneous squamous cell carcinoma and basal cell carcinoma. AB - PURPOSE: To analyze the prevalence and significance of FOXP3+ infiltration into (pre)malignant skin carcinomas following ultraviolet radiation (UVR) exposure. The possible pathways that UVR impacts on FOXP3 are to be discussed. BACKGROUND: FOXP3+ regulatory T cells (FOXP3+ Tregs) are correlated to cutaneous squamous tumor progression. However, there is no information describing the prevalence of FOXP3+ infiltration in cutaneous premalignant and malignant squamous carcinomas with UVR exposure. METHODS: We investigated the prevalence of FOXP3+ infiltration in 14 patients with Bowen's disease, 40 squamous cell carcinoma SCC patients and 21 patients with basal cell carcinoma (BCC) by immunohistochemistry. RESULTS: The percentages of FOXP3+ vs. total peri-neoplasm infiltration cells (FOXP3+ PCT) were significantly higher in Bowen's disease and well-differentiated SCC that were exposed to UVR than these diseases not exposed to UVR (t = 3.5776, P = 0.0038; t' = 5.9214, P < 0.01, respectively). FOXP3+ PCT was also higher in less pigmented than pigmented sites in BCC (t = 3.369, P = 0.0032). CONCLUSIONS: This study shed some light on the effect of UVR on FOXP3+ infiltration in skin (pre)malignant carcinomas. Our data suggested that FOXP3+ infiltration was positively related to UVR exposure. The mechanisms merit further investigation. PMID- 22092734 TI - Vitamin D serum level changes in psoriatic patients treated with narrowband ultraviolet B phototherapy are related to the season of the irradiation. AB - BACKGROUND: Vitamin D is produced in the human skin by short wavelength (290-315 nm) ultraviolet (UV) radiation. PURPOSE: The aim of the study was to investigate how outdoor conditions may influence the serum levels of 25(OH) vitamin D in psoriasis patients under narrowband ultraviolet B (UVB) phototherapy. METHODS: The winter and summer groups of patients received almost the same narrowband UV (nUVB) doses during whole-body phototherapy. The 25(OH)D serum concentration was measured before and after two series of 10 exposures. The cabinet doses were compared with potentially available cumulative solar doses. The solar doses (unweighted UVB and vitamin D effective dose) and duration of solar intensity sufficient to produce vitamin D were calculated using a model based on local atmospheric data. RESULTS: After an initial 10 nUVB treatments, 25(OH)D serum concentration increased by 68% for winter patients in relation to the level before therapy, whereas a 20% increase was found for the summer patients. The next 10 treatments caused a much lower increase in 25(OH)D concentration: 5% and 3.5% for the winter and summer patients, respectively. No statistically significant relationship was observed between post-therapy 25(OH)D serum concentration and solar radiation variability. CONCLUSIONS: The different baseline values of 25(OH)D serum levels in winter and summer patients result from seasonal variability in solar irradiance. Thus, outdoor solar radiation affects the patients over a much longer period, and artificial UV light is the main factor responsible for increase in 25(OH)D serum level over a 30-day period of cabinet therapy. PMID- 22092735 TI - Ultraviolet exposure for different outdoor sports in Valencia, Spain. AB - BACKGROUND: The purpose of this study is to quantify ultraviolet (UV) exposure of several groups of amateur athletes in their training or recreational schedules. METHODS: The athletes were monitored using dosimeters (VioSpor).The study took place in Valencia, Spain, from May to July 2010, and involved a group of 10 mountaineers, four tennis players and five runners. RESULTS: The mean daily personal UV exposure for mountaineers was 9.48 +/- 3.23 standard erythema dose (SED). The tennis players received a mean of 10.65 +/- 1.57 SED for every 2 days of training, and the runners received a mean of 7.62 +/- 4.28 SED for every 5 days of training. CONCLUSION: Mountaineers received a higher dose of UV exposure and have a higher exposure ratio than the tennis players, probably because they spent more time outdoors. However, the runners received a low dose of UV exposure, perhaps because their training takes place in the evening. Mean daily UV exposure of the mountaineers and tennis players exceeded 5 SED, which means that, in the case of non-sun-adapted skin type III and the non-use of sun protection, erythema may be induced in these subjects. Accordingly, it is necessary to encourage the use of high protection sunscreens and protective clothing, and to avoid UV exposure in the hottest part of the day. PMID- 22092736 TI - UVA-activated synthesis of metalloproteinases 1, 3 and 9 is prevented by a broad spectrum sunscreen. AB - BACKGROUND: Specific sunscreens against ultraviolet (UV) A and B radiations are essential to prevent matrix degradation and the activation of intracellular signaling pathways involved in photoaging and photocarcinogenesis. Matrix degradation results from UVA-induced production of matrix metalloproteinases (MMP) and activation of intracellular pathways in fibroblasts and keratinocytes. In particular, in keratinocytes, UVA radiation induces beta-catenin nuclear translocation and stimulates MMP gene transcription. Our study was aimed at assessing the efficacy of a specific broad-spectrum sunscreen in preventing beta catenin translocation and MMPs enhanced expression in cultured keratinocytes after UVA irradiation. METHODS: Sunscreen or the vehicle was spread on quartz sheet. Irradiation of HaCaT cells with 6 J/cm(2) UVA was performed through the sheet, and cells were collected for beta-catenin immunostaining then visualization by confocal microscopy, and quantitative real-time polymerase chain reaction analysis of MMP-1, -3 and -9 gene expression. RESULTS: As shown by immunostaining and confocal microscopy, the sunscreen abrogated UVA-induced beta catenin translocation to the nucleus, in comparison with control groups. MMP-1, 3 and -9 mRNA expression was enhanced by 7, 7 and 4 folds (P < 0.0001, P < 0.001 and P < 0.01, respectively) in unprotected UVA-irradiated cells compared to the non-irradiated control. Sunscreen protection of the cells significantly reduced UVA-induced expression of MMP-1, -3 and -9 by 83% (P < 0.01), 80% (P < 0.01) and 65% (P < 0.05), respectively. CONCLUSION: This study demonstrated the efficacy of this broad-spectrum sunscreen in preventing UVA-induced effects on the markers of photoaging and photocarcinogenesis in vitro. It was able to protect HaCaT keratinocytes from UVA-induced beta-catenin translocation to the nucleus and MMPs expression. PMID- 22092737 TI - Narrowband ultraviolet B phototherapy for alopecia areata. AB - Although narrowband ultraviolet B (NB UVB) phototherapy is a well-established treatment in many dermatosis, there is little evidence of efficacy of this method for alopecia areata (AA) treatment in the literature. We undertook a retrospective review of the 25 AA patients treated with NB UVB. Intramuscular triamcinolone acetonide injections per month were used as concomitant treatment in some patients who did not have any contraindication. Eight patients (32%) received monthly intramuscular corticosteroid injections. Four (22.2%) and two (20%) patients achieved excellent response in extensive patchy hair loss patients and entire scalp hair loss patients, respectively. Four of six patients who achieved excellent response also received monthly intramuscular corticosteroid injections. When patients receiving systemic corticosteroid injections were compared with patients given only NB UVB with respect to the treatment responses, a statistically significant difference was seen in patients who achieved excellent response. NB UVB is not an effective treatment with only 20% excellent treatment responses in patients with severe AA, most of whom were also treated with systemic corticosteroids. PMID- 22092738 TI - Dysfunction of melanocytes in photoleukomelanoderma following photosensitivity caused by hydrochlorothiazide. AB - We report a 68-year-old Japanese man who developed photoleukomelanoderma following prolonged photosensitivity caused by hydrochlorothiazide. He showed complete recovery from the leukomelanoderma with the discontinuation of the responsive drug and with topical application of tacrolimus hydrate and corticosteroid. Histological and immunohistochemical examination revealed that there were no melanin-positive cells in the hypopigmented area, despite the presence of melanocytes. These results and the clinical course indicate that leukomelanoderma is postulated temporary dysfunction of melanocytes. We also conducted a review of previous case reports regarding drug-induced photoleukomelanoderma. PMID- 22092739 TI - The impact of ultraviolet therapy on stratum corneum ceramides and barrier function. AB - The ceramide profile as well as the barrier function is known to be deteriorated in atopic eczema and psoriasis, and ultraviolet (UV) light is known to improve the barrier function. The impact of UV light on ceramides, however, is not clarified. The aim of this study was to examine the effect of UV therapy in dermatological patients on ceramides and skin barrier function. We found that UV light treatment does not change the ratio of important stratum corneum lipids, but we confirm earlier findings of decreased susceptibility to irritants after UV therapy. PMID- 22092740 TI - Photodynamic therapy for a hypertrophic scarring: a promising choice. AB - The case we report is about a female patient, 69 years old, who had a hypertrophic scarring on the right cheek because of a bite by her dog. She had attempted many types of topical and intralesional treatments but without success. The patient underwent photodynamic therapy (PDT), employing a methyl ester of 5 aminolevulinic acid (MAL) as topical photosensitizer and a non-coherent red light at a wavelength of 632 nm. This session was then repeated three more times at 2 week intervals. A month after the last session, the scarred area significantly softened, becoming more flexible, less erythematous, smoother and reduced in volume. The patient was greatly satisfied with the clinical and cosmetic result, she had no more than rough scarring on the cheek, and her skin in the area around the lesion was very smooth, wrinkle-free. She did not show any recurrence of her hypertrophic scarring after 1 year of follow-up. PDT revealed to be the most effective approach if compared with previous therapeutic options received by the patient, but further studies are necessary to evaluate protocols to be used for the best results in this kind of application. PMID- 22092741 TI - Failure of omalizumab (Xolair(r)) in the treatment of a case of solar urticaria caused by ultraviolet A and visible light. AB - Solar urticaria is a rare photodermatosis probably caused by a chromophore, that if activated by light of a specific spectrum - binds to mast cell-bound IgE and elicits degranulation. In our patient an action spectrum in ultraviolet A and visible light range was found, in the autologous serum test the presence of a serum chromophore for the same action spectra could be demonstrated, which may underline this pathogenetic hypothesis. Symptoms did not improve using antihistamines and sun protection. Photo hardening was denied from the patient, immunosuppression and plasmapheresis were discussed but not considered. So a treatment with Omalizumab was started that recently was successfully used in 4 case reports. After 3 doses of Xolair(r) there was no changing in the phototesting results and after 4 doses no subjective improvement. PMID- 22092742 TI - Photosensitivity induced by naproxen. AB - We present two cases of systemic photosensitivity due to naproxen that presented as photodistributed erythema multiforme (EM) and lichenoid photodermatitis (LP). Although naproxen is a commonly used nonsteroidal antinflammatory drug and has the capacity of causing systemic photosensitivity, there are very few reports about it in the literature. The diagnosis was suspected by the recent ingestion of the drug and the photodistribution of the lesions. A positive photopatch test in the first patient and the normalization of the MED-UVB after discontinuing naproxen in the second patient supported the diagnosis. PMID- 22092743 TI - Quantitative method for measuring therapeutic efficacy of the 308 nm excimer laser for vitiligo. AB - BACKGROUND: There are several available treatments for vitiligo, but measurement of their therapeutic efficacy is not standardized and is somewhat arbitrary based largely on the global impression of the overall response. The purpose of this study was to develop a quantitative method for evaluating the treatment response of vitiligo measuring changes in area using digital image analysis. We applied this parametric model to the evaluation of efficacy of the 308 nm excimer laser. METHODS: This study was a retrospective study, designed as a before and after trial with a single arm. A total of 18 patients were enrolled who had been treated with a 308 nm excimer laser as monotherapy twice a week for 20 sessions. The repigmentation percentage was calculated by measuring changes in area before and after treatment using digital image analysis and graded on a five-point ordinal scale [global assessment scale (GAS)]. GAS was also measured by physician and patient for comparison with our estimates. Additional GASs were also measured by four different evaluators for inter-rater variability. RESULTS: The mean repigmentation percentage after treatment was 45.3% (range, 0.7-100%). The changes in area after treatment were statistically significant (P < 0.05). A substantial agreement of outcomes was observed between physicians and digital image analysis (kappa(w) = 0.78), but lower agreement was observed between patients and digital image analysis (kappa(w) = 0.49). The inter-rater variability for GAS was substantially low (Krippendorff's alpha = 79.3%). CONCLUSION: Measurement of changes in area using digital image analysis could be used as a quantitative method in evaluating efficacy of treatment for vitiligo. Because vitiligo lesions can occur in any location with various shapes and sizes, digital image analysis would be a more objective method for measuring treatment response than a GAS. PMID- 22092744 TI - Matrix metalloproteinase-8 expression in periodontal tissues surgically removed from diabetic and non-diabetic patients with periodontal disease. AB - BACKGROUND: Although it is known that periodontal matrix metalloproteinase-8 (MMP 8) expression is associated with periodontal disease, the information concerning the periodontal MMP-8 expression in diabetic patients with periodontal disease is insufficient. MATERIALS AND METHODS: Periodontal tissue specimens were collected from seven patients without periodontal disease and diabetes (Group 1), 15 patients with periodontal disease alone (Group 2) and 10 patients with both periodontal disease and diabetes (Group 3). The frozen sections were prepared and MMP-8 protein expression was detected using immunohistochemistry and quantified. For in vitro study, human U937 mononuclear cells were pre-exposed to normal or high glucose and then treated with lipopolysaccharide (LPS). RESULTS: The nonparametric Kruskal-Wallis test showed that the difference in MMP-8 protein levels among the three groups were statistically significant (p = 0.003). Nonparametric analysis using Jonckheere-Terpstra test showed a tendency of increase in periodontal MMP-8 levels across Group 1 to Group 2 to Group 3 (p = 0.0002). In vitro studies showed that high glucose and LPS had a synergistic effect on MMP-8 expression. CONCLUSION: Our current study showed an increasing trend in MMP-8 protein expression levels across patients without both periodontal disease and diabetes, patients with periodontal disease alone and patients with both diseases. PMID- 22092745 TI - Supportive periodontal therapy and dental implants: an analysis of patients' compliance. AB - OBJECTIVES: The purpose of this retrospective study was to evaluate the compliance to supportive periodontal therapy (SPT) in a population of adult periodontal patients, and to determine the impact of clinical procedures performed such as the type of active periodontal therapy and the insertion of dental implants. MATERIAL AND METHODS: Ninety-six patients were evaluated. The subjects were divided into two groups, according to the active periodontal procedure (surgical/non-surgical), and were also classified as having or not having osseointegrated implants. The number of visits for SPT after the end of active therapy was evaluated, and subjects were classified as compliant or non compliant. RESULTS: At the end of a 5-year evaluation, 77.1% of patients completely complied with SPT while 22.9% of patients had insufficient compliance degree. No significant difference was found in compliance between subjects that had surgical or non-surgical periodontal treatment. However, patients that had the insertion of one or more dental implant registered a significant higher degree of compliance than patients that had no fixtures insertion. CONCLUSION: The results suggest that it is possible to have excellent degree of patients' compliance for SPT. The performance of periodontal surgical therapy itself is not a reason able to motivate the patients to maintenance care, while the insertion of osseointegrated implants seems to be a reliable reason to positively affect the compliance with SPT. PMID- 22092746 TI - Serum resistance in Haemophilus parasuis SC096 strain requires outer membrane protein P2 expression. AB - Haemophilus parasuis outer membrane protein P2 (OmpP2), the most abundant protein in the outer membrane, has been identified as an antigenic protein and a potential virulence factor. To study the precise function of OmpP2, an ompP2 deficient mutant (DeltaompP2) of a H. parasuis serovar 4 clinical strain SC096 was constructed by a modified natural transformation system. Compared with the wild-type SC096 strain, the DeltaompP2 mutant showed a pronounced growth defect and exhibited significantly greater sensitivity to the bactericidal action of porcine and rabbit sera, whereas the complemented strain could restore the growth and serum resistance phenotypes. The results indicated that H. parasuis OmpP2 from SC096 strain is an important surface protein involved in serum resistance. PMID- 22092747 TI - Inflammation and oxidative stress are lower in physically fit and active adults. AB - The objective of this study was to determine if the inverse relationship between perceived physical fitness (pFIT) and exercise frequency (ExFreq) levels and chronic inflammation and oxidative stress exists after making statistical adjustments for confounders including body mass index (BMI), age, gender, and cigarette smoking. Study participants (60% female and 40% male; n = 998) varied widely in age (18-85 years) and BMI (16.7-52.7 kg/m(2)) completed an extensive medical/health and lifestyle questionnaire, and data were used to establish pFIT and ExFreq tertiles. Biomarkers included serum C-reactive protein (CRP), total blood leukocytes, five plasma cytokines [interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP1), and granulocyte colony-stimulating factor (GCSF)], F2 -isoprostanes, ferric reducing ability of plasma (FRAP), and oxygen radical absorbance capacity (ORAC). A general linear model was used to examine relationships between pFIT and ExFreq with inflammation and oxidative stress while controlling for age, gender, BMI, and smoking. Benjamini-Hochberg method for false discovery rate correction was used for multiple testing corrections. Significant tests (P < 0.05) for trend were found for the effect of pFIT and ExFreq on CRP, white blood cell, IL-6, TNF alpha, GCSF, and F2 -isoprostanes, but not MCP1, IL-10, FRAP, and ORAC, after adjustment for confounders. These data indicate that an inverse relationship exists among chronic inflammation, oxidative stress, and pFIT and ExFreq at the community level even after adjustment for important confounders. PMID- 22092748 TI - Microdontia and hypodontia of premolars and permanent molars in childhood cancer survivors after chemotherapy. AB - BACKGROUND: Adverse long-term general and dental health effects of cancer and cancer therapy during childhood have been reported. AIM: To examine the association between chemotherapy before the age of 8 years and (1): microdontia; (2): hypodontia of premolars and permanent molars. MATERIAL AND METHODS: In The Danish Registry of Childhood Cancer (DBCR), we identified 203 children who met the following inclusion criteria: (1) age below 8 years at the start of treatment; (2) age between 12 to 18 years upon dental examination; (3) had received chemotherapy The exclusion criterion was radiotherapy to the head and neck. A total of 150 children fulfilled the inclusion criteria. As controls, a random sample of 193 age-matched unexposed children was included. RESULTS: Microdontia was found in a total of 88 teeth in 29 (19.3%) of the 150 children who had been exposed to chemotherapy, while none of the controls had microdontia of premolars or permanent molars (difference: 19.3%; 95% CL: 13.5%; 26.4%). The earlier the exposure, the more frequent was microdontia. We found a total of 27 missing premolars and permanent molars in 14 (9.3%) of the exposed children and a total of 18 missing premolars and permanent molars in 8 (4.1%) of the controls (difference: 5.2%; 95% CL: -0.1%; 11.3%). CONCLUSION: The present study confirms findings from previous studies that chemotherapy, especially in very young children, causes microdontia and hypodontia of premolars and permanent molars. PMID- 22092749 TI - Increased chitinase expression and fungal-specific antibodies in the bronchoalveolar lavage fluid of asthmatic children. AB - BACKGROUND: Increasing evidence highlights the contribution of chitinases and fungal infection to the development of asthma. OBJECTIVE: The purpose of this study was to characterize chitinase expression and serological markers of fungal infection in children with severe asthma. METHODS: Bronchoalveolar lavage fluid (BALF) was collected from children undergoing clinically indicated flexible bronchoscopy. A diagnosis of asthma was confirmed by pulmonary function testing. BALF was tested for chitinase activity and YKL-40 (an enzymatically inactive chitinase) concentrations. Specimens were cultured for fungal organisms and tested for cryptococcal antigen by ELISA. IgG and IgA reactivity to whole extract fungal (Aspergillus fumigatus, Alternaria alternata, Cryptococcus neoformans and Candida albicans) proteins were determined by immunoblot assay. RESULTS: Among the 37 patients studied, 30 were asthmatic and 7 were non-asthmatic. Asthmatics exhibited elevated serum IgE levels (median: 748 IU/mL, IQR: 219-1765 IU/mL). Chitinase activity was greater in the BALF of asthmatics (mean, 0.85 +/- 1.2 U/mL) compared with non-asthmatics (mean: 0.23 +/- 0.21 U/mL, P = 0.012). Likewise YKL-40 concentrations were higher in the BALF of asthmatics and correlated with chitinase activity. There was a trend towards increased fungal specific IgG in the BALF of asthmatics compared with non-asthmatics and for C. albicans this difference reached statistical significance. IgA reactivity to C. neoformans and A. fumigatus was greater in the BALF of asthmatics compared with non-asthmatics. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with non-asthmatics, asthmatic children exhibited increased chitinase activity and increased YKL-40 levels in BALF. Increased IgG and IgA reactivity to fungal proteins in the BALF of asthmatics may reflect a local response to fungal infection. Our findings are consistent with and suggest a role for chitinases in asthma pathogenesis among Bronx children and provide serological evidence of an association between fungal infection and severe asthma. PMID- 22092750 TI - Estimation of effective concentrations of ATP-regenerating enzymes in cilia of Paramecium caudatum. AB - The phosphoarginine shuttle system effectively regenerates ATP in the cilia of Paramecium caudatum. To estimate the effective concentration of ATP-regenerating enzymes, we attempted to reconstitute certain ATP-regenerating systems within the cilia of intact cortical sheets using exogenous enzymes and high-energy substances. The addition of phosphoenolpyruvate, which is one of the substrates in glycolysis, did not increase the ciliary beat frequency, whereas phosphocreatine together with exogenous creatine kinase, effectively increased the ciliary beat frequency. In the presence of 0.6 mg/ml creatine kinase and 0.4 mM phosphocreatine, the ciliary beat frequency was comparable to that produced by the addition of phosphoarginine. This result indicates that the reconstituted phosphocreatine shuttle system can work as an artificial ATP-regenerating system for ciliary movements. The effective concentration of creatine kinase in the reconstituted phosphocreatine shuttle system was estimated to be about 7.4 MUM based on the molecular mass of creatine kinase (MW 81,000). Therefore, the effective concentration of arginine kinase in the cilia of live Paramecium is approximately 10 MUM. This estimated concentration of intraciliary arginine kinase is sufficient to maintain a high ATP concentration throughout the cilia of P. caudatum. PMID- 22092751 TI - Duplication of the great saphenous vein: a definition problem and implications for therapy. AB - BACKGROUND: In the literature there is a range from 1% to 20 % of duplication (up to 20%) of the great saphenous vein (GSV) reported, because there is a lack of an accurate definition of the GSV and objective parameters for an anatomical identification. OBJECTIVE: To investigate the frequency of true duplications of the GSV. MATERIALS AND METHODS: A systematic review of the literature, a retrospective analysis of duplex examinations, and a prospective study of duplex examinations to investigate the frequency of true duplications of the GSV. RESULTS: In the literature review, a great variety of definitions is used for duplication of the GSV. Before the consensus of the Union International de Phlebologie (UIP) in 2006, Only in a small number of studies, the definition of the GSV in the saphenous compartment between the fascial blades is mentioned. CONCLUSION: Phlebographic studies have been the criterion standard for the identification of venous anatomy. Now, duplex is regarded as the criterion standard for accurate detection of the veins. True duplication of the GSV is less common than the previous literature has suggested, namely 1.6% to 2%. It is recommended that the duplicated GSV should be treated to avoid an important risk of recurrence of venous insufficiency. PMID- 22092752 TI - Laser tattoo removal: a review. AB - BACKGROUND: Tattoos have played an important role in human culture for thousands of years, and they remain popular today. The development of quality-switched (QS) lasers has revolutionized the removal of unwanted tattoos. OBJECTIVES: To thoroughly review the literature on laser tattoo removal pertaining to its history, its theoretical basis, the various devices used, potential adverse effects, and future developments. MATERIAL AND METHODS: An extensive literature review of publications related to tattoo removal was conducted. RESULTS: Reports exist demonstrating the efficacy of laser removal of different tattoo types, including professional, amateur, traumatic, cosmetic, and medical. The literature supports the use of different QS lasers for removal of tattoos. Some colors have a more-complete response using particular wavelengths. CONCLUSION: QS lasers can effectively and safely remove different types of unwanted tattoos. PMID- 22092753 TI - Preliminary molecular identification of cylindrospermopsin-producing Cyanobacteria in two Polish lakes (Central Europe). AB - The presence of toxigenic cyanobacteria capable of biosynthesis of cylindrospermopsin (CYN) was measured in 24 water samples collected from the lakes Bytynskie (BY) and Bninskie (BN) in the Western Poland. The study also covered analysis of toxigenicity and production of CYN by the culture of Cylindrospermopsis raciborskii isolated from BY. The cyrJ gene associated with CYN production was identified in 22 water samples collected in the summer seasons of 2006 and 2007. The presence of CYN was confirmed in 16 samples. The homology searches revealed that amplified sequences of four water samples, which were selected from among all the samples, displayed a strong 99% homology to cyrJ gene of Aphanizomenon sp. 10E6. The culture of C. raciborskii did not contain the cyrJ gene nor the CYN. The specificity of C. raciborskii was confirmed by application of a fragment of the rpoC1. These first genetic analyses have shown that Aphanizomenon seems to be the main cyanobacterial genus responsible for the production of CYN in the Polish lakes. The lack of toxigenicity of the isolated C. raciborskii suggests that it is possible that this invasive species does not demonstrate toxigenic activity in Polish water bodies. PMID- 22092754 TI - Expanding the mycobacterial diversity of metalworking fluids (MWFs): evidence showing MWF colonization by Mycobacterium abscessus. AB - Nontuberculous mycobacteria (NTM) have been associated with hypersensitivity pneumonitis in machinists. Only two species of NTM, namely Mycobacterium immunogenum and Mycobacterium chelonae, have been reported thus far to have the ability to colonize contaminated metalworking fluids (MWFs). Here, we report, for the first time, the presence and characterization (phenotypic and genotypic) of a third species, Mycobacterium abscessus, colonizing these harsh alkaline machining fluids. Two Mycobacterium morphotypes, smooth (S) and rough (R), were isolated (two isolates each) from an in-use industrial MWFs. Biocide susceptibility analysis using triclosan as a model yielded the same minimal inhibitory concentration for the two morphotypes. PCR-restriction analysis-based speciation of the morphotypes confirmed their identity as M. abscessus. Genotyping based on partial DNA sequences corresponding to the variable regions of the hsp65 gene and 16S-23S rRNA operon internal transcribed spacer region and randomly amplified polymorphic DNA-PCR analysis showed that both morphotypes belong to a single genotype. In addition, we isolated and confirmed two novel mycobacterial genotypes, one each of M. immunogenum and M. chelonae from additional in-use MWF screening. Taken together, this study expands the known mycobacterial species- and strain-diversity colonizing MWF. Furthermore, the study emphasizes the need for including M. abscessus species in the existing mycobacterial screening of contaminated MWF. PMID- 22092755 TI - Phylogenetic characterization of bacteria in the gut of house flies (Musca domestica L.). AB - House flies (Musca domestica L.) are cosmopolitan, ubiquitous, synanthropic insects that serve as mechanical or biological vectors for various microorganisms. To fully assess the role of house flies in the epidemiology of human diseases, it is essential to understand the diversity of microbiota harbored by natural fly populations. This study aimed to identify the diversity of house fly gut bacteria by both culture-dependent and culture-independent approaches. A total of 102 bacterial strains were isolated from the gut of 65 house flies collected from various public places including a garden, public park, garbage/dump area, public toilet, hospital, restaurant/canteen, mutton shop/market, and house/human habitation. Molecular phylogenetic analyses placed these isolates into 22 different genera. The majority of bacteria identified were known potential pathogens of the genera Klebsiella, Aeromonas, Shigella, Morganella, Providencia, and Staphylococcus. Culture-independent methods involved the construction of a 16S rRNA gene clone library, and sequence analyses supported culture recovery results. However, additional bacterial taxa not determined via culture recovery were revealed using this methodology and included members of the classes Alphaproteobacteria, Deltaproteobacteria, and the phylum Bacteroidetes. Here, we show that the house fly gut is an environmental reservoir for a vast number of bacterial species, which may have impacts on vector potential and pathogen transmission. PMID- 22092756 TI - Three-dimensional bone structure and bone mineral density evaluations of autogenous bone graft after sinus augmentation: a microcomputed tomography analysis. AB - OBJECTIVE: The purpose of this study was to determine the relationships and differences in three-dimensional (3D) bone mineral density (BMD) and microtrabecular structures between autogenous bone grafts and their adjacent native bone after a healing period following maxillary sinus augmentation. MATERIALS AND METHODS: Nine rod-shaped human bone biopsy samples were taken from patients receiving two-stage sinus augmentation therapy in implantation areas and analyzed using microcomputed tomography (micro-CT). Before micro-CT scanning, two BMD phantoms were placed near to the bone biopsy samples for executing BMD calculations of the grafted and native bone samples. In addition, 3D structural parameters of the trabeculae were analyzed for both the grafted and native bone, including percentage of bone volume [bone volume (BV)/tissue volume (TV)], bone specific surface [bone surface (BS)/BV], trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular pattern factor (Tb.Pf), and structure model index (SMI). RESULTS: No significant correlations with regard to BMD and trabecular-structure parameters were found between native bone and grafted bone; however, BS/BV and Tb.Pf were higher and Tb.Th and Tb.Sp were 37.35% and 12.74% lower in grafted bone than in native bone. For grafted bone, there were significant correlations (P < 0.05) between BMD and BV/TV, and Tb.N. CONCLUSIONS: When using autogenous bone as a graft material, BMD and micromorphological conditions of grafted bone were not influenced by the condition of the native bone in the maxilla. Differences were found in surface complexity, trabecular thickness, trabecular separation, and the connectivity of trabeculae between grafted and native bone. The BMD in grafted bone was affected by the quantity of the trabeculae. PMID- 22092757 TI - Histoplasma mechanisms of pathogenesis--one portfolio doesn't fit all. AB - Histoplasma capsulatum is the leading cause of endemic mycosis in the world. Analyses of clinical isolates from different endemic regions show important diversity within the species. Recent molecular studies of two isolates, the Chemotype I NAm2 strain G217B and the Chemotype II Panamanian strain G186A, reveal significant genetic, structural, and molecular differences between these representative Histoplasma strains. Some of these variations have functional consequences, representing distinct molecular mechanisms that facilitate Histoplasma pathogenesis. The realization of Histoplasma strain diversity highlights the importance of characterizing Histoplasma virulence factors in the context of specific clinical strain isolates. PMID- 22092759 TI - Saliva promotes survival and even proliferation of Candida species in tap water. AB - Candida yeasts colonize the human oral cavity as commensals or opportunistic pathogens. They may be isolated from water circulating in dental unit waterlines mixed with traces of saliva mainly because of the dysfunction of antiretraction valves. This study deals with the growth ability of Candida albicans, Candida glabrata and Candida parapsilosis in tap water with saliva (0-20% v/v). Results show that C. glabrata is the most susceptible species in tap water. Furthermore, saliva promotes both survival and proliferation of the three studied Candida species in tap water. PMID- 22092758 TI - NADPH-dependent pgi-gene knockout Escherichia coli metabolism producing shikimate on different carbon sources. AB - We explored the physiological and metabolic effects of different carbon sources (glucose, fructose, and glucose/fructose mixture) in phosphoglucose isomerase (pgi) knockout Escherichia coli mutant producing shikimic acid (SA). It was observed that the pgi(-) mutant grown on glucose exhibited significantly lower cell growth compared with the pgi(+) strain and its mixed glucose/fructose fermentation grew well. Interestingly, when fructose was used as a carbon source, the pgi(-) mutant showed the enhanced SA production compared with the pgi(+) strain. In silico analysis of a genome-scale E. coli model was then conducted to characterize the cellular metabolism and quantify NAPDH regeneration, which allowed us to understand such experimentally observed attenuated cell growth and enhanced SA production in glucose- and fructose-consuming pgi(-) mutant, respectively with respect to cofactor regeneration. PMID- 22092760 TI - Variation and predicted structure of the flagellin gene in Actinoplanes species. AB - Members of the genus Actinoplanes are considered to be representative of motile actinomycetes. To infer the flagellar diversity of Actinoplanes species, novel degenerate primers were designed for the flagellin (fliC) gene. The fliC gene of 21 Actinoplanes strains was successfully amplified and classified into two groups based on whether they were large (type I) or small (type II). Comparison of the translated amino acid sequences revealed that this size difference could be attributed to large number of gaps located in the central variable region. However, the C- and N- terminal regions were conserved. Except for a region on the flagellum surface, structural predictions of type I and II flagellins revealed that the two flagellin types were strongly correlated with each other. Phylogenetic analysis of the 115-amino acid N-terminal sequences revealed that the Actinoplanes species formed three clusters, and type II flagellin gene containing three type strains were phylogenetically closely related each other. PMID- 22092761 TI - Development of antibiotic resistance and up-regulation of the antimutator gene pfpI in mutator Pseudomonas aeruginosa due to inactivation of two DNA oxidative repair genes (mutY, mutM). AB - Prevention and correction of oxidative DNA lesions in Pseudomonas aeruginosa is ensured by the DNA oxidative repair system (GO). Single inactivation of mutT, mutY and mutM involved in GO led to elevated mutation rates (MRs) that correlated to increased development of resistance to antibiotics. In this study, we constructed a double mutant in mutY and mutM (PAOMY-Mgm) and characterized the phenotype and the gene expression profile using microarray and RT-PCR. PAOMY-Mgm presented 28-fold increases in MR compared with wild-type reference strain PAO1. In comparison, the PAOMYgm (mutY) single mutant showed only a fivefold increase, whereas the single mutant PAOMMgm (mutM) showed a nonsignificant increase in MR compared with PAO1 and the single mutants. Mutations in the regulator nfxB leading to hyperexpression of MexCD-OprJ efflux pump were found as the mechanism of resistance to ciprofloxacin in the double mutant. A better fitness of the mutator compared with PAO1 was found in growth competition experiments in the presence of ciprofloxacin at concentrations just below minimal inhibitory concentration. Up-regulation of the antimutator gene pfpI, that has been shown to provide protection to oxidative stress, was found in PAOMY-Mgm compared with PAO1. In conclusion, we showed that MutY and MutM are cooperating in the GO of P. aeruginosa, and that oxidative DNA lesions might represent an oxidative stress for the bacteria. PMID- 22092762 TI - Cloning, expression analysis, and sequence diversity of genes encoding two different immunodominant membrane proteins in poinsettia branch-inducing phytoplasma (PoiBI). AB - Poinsettia branch-inducing phytoplasma (PoiBI) is a phytopathogenic bacterium that infects poinsettia, and is associated with the free-branching morphotype (characterized by many axillary shoots and flowers) of many commercially grown poinsettias. The major membrane proteins of phytoplasmas are classified into three general types, that is, immunodominant membrane protein (Imp), immunodominant membrane protein A (IdpA), and antigenic membrane protein (Amp). These membrane proteins are often used as targets for the production of antibodies used in phytoplasma detection. Herein, we cloned and sequenced the imp and idpA genes of PoiBI strains from 26 commercial poinsettia cultivars. Although the amino acid sequences of the encoded IdpA proteins were invariant, those of the encoded Imp varied among the PoiBI isolates, with no synonymous nucleotide substitution. Western blotting and immunohistochemical analyses revealed that the amount of Imp expressed exceeded that of IdpA, in contrast to the case of a related phytoplasma-disease, western X-disease, for which the major membrane protein appears to be IdpA, not Imp. These results suggest that even phylogenetically close phytoplasmas express different types of major membrane proteins. PMID- 22092763 TI - Fbl is not involved in the invasion of eukaryotic epithelial and endothelial cells by Staphylococcus lugdunensis. AB - For several Staphylococci, such as Staphylococcus aureus, Staphylococcus saprophyticus, and Staphylococcus epidermidis, invasion of eukaryotic cells has been described and this mechanism has been considered an important part of the infection process. The fibrinogen-binding protein (Fbl) of Staphylococcus lugdunensis, a homolog of the clumping factor A of S. aureus, has been described as fibrinogen-binding adhesin and might promote invasion of cells. We therefore characterized several clinical strains of S. lugdunensis in terms of whole cell fibrinogen and fibronectin binding and correlated these results with the invasion of epithelial and endothelial cells by S. lugdunensis. We described for the first time invasion of cells by S. lugdunensis. As invasion of cells by S. lugdunensis was only partly inhibited by cytochalasin D in contrast to a complete inhibition of invasion of cells by S. aureus, further invasion mechanisms are likely to be present in S. lugdunensis. In addition, the Fbl of S. lugdunensis is not involved in the invasion of cells as ruled out by an isogenic fbl mutant. PMID- 22092764 TI - Functional characterization of the type II PamI restriction-modification system derived from plasmid pAMI7 of Paracoccus aminophilus JCM 7686. AB - Plasmid pAMI7 of the methylotrophic bacterium Paracoccus aminophilus JCM 7686 (Alphaproteobacteria) encodes a functional type II restriction-modification (R-M) system designated PamI. Homologous systems were identified in the genomes of distinct taxonomic groups of Bacteria and Archaea, which provides evidence that horizontal gene transfer has contributed to the wide dissemination of R-M modules - even between domains. Analysis of the cleavage specificity of the R.PamI endonuclease revealed that this protein is an isoschizomer of restriction enzyme NcoI. Interestingly, bioinformatic analyses suggest that R.PamI and NcoI are accompanied by methyltransferases of different methylation specificities (C5 methylcytosine and N4-methylcytosine methyltransferases, respectively), which possibly exemplifies recombinational shuffling of genes coding for individual components of R-M systems. The PamI system can stabilize plasmid pAMI7 in a bacterial population, most probably at the postsegregational level. Therefore, it functions in an analogous manner to plasmid-encoded toxin-antitoxin (TA) systems. Since the TA system of pAMI7 is nonfunctional, it is highly probable that this lack is compensated by the stabilizing activity of PamI. This indicates the crucial role of the analyzed R-M system in the stable maintenance of pAMI7, which is, to our knowledge, the first report of 'symbiosis' between a R-M system and a plasmid in the Alphaproteobacteria. PMID- 22092765 TI - Effects of microplusin, a copper-chelating antimicrobial peptide, against Cryptococcus neoformans. AB - Microplusin is an antimicrobial peptide isolated from the cattle tick Rhipicephalus (Boophilus) microplus. Its copper-chelating ability is putatively responsible for its bacteriostatic activity against Micrococcus luteus as microplusin inhibits respiration in this species, which is a copper-dependent process. Microplusin is also active against Cryptococcus neoformans (MIC(50) = 0.09 MUM), the etiologic agent of cryptococcosis. Here, we show that microplusin is fungistatic to C. neoformans and this inhibitory effect is abrogated by copper supplementation. Notably, microplusin drastically altered the respiratory profile of C. neoformans. In addition, microplusin affects important virulence factors of this fungus. We observed that microplusin completely inhibited fungal melanization, and this effect correlates with the inhibition of the related enzyme laccase. Also, microplusin significantly inhibited the capsule size of C. neoformans. Our studies reveal, for the first time, a copper-chelating antimicrobial peptide that inhibits respiration and growth of C. neoformans and modifies two major virulence factors: melanization and formation of a polysaccharide capsule. These features suggest that microplusin, or other copper chelation approaches, may be a promising therapeutic for cryptococcosis. PMID- 22092766 TI - The Vibrio parahaemolyticus pvuA1 gene (formerly termed psuA) encodes a second ferric vibrioferrin receptor that requires tonB2. AB - We previously reported that the Vibrio parahaemolyticus pvsABCDE and psuA pvuABCDE operons are involved in the biosynthesis and transport of its own siderophore, vibrioferrin (VF). Of these, psuA and pvuA encode TonB-dependent outer-membrane proteins (OMPs). Although pvuA was characterized as the ferric vibrioferrin receptor gene, the role of the psuA product remains unknown. In this study, a growth assay of isogenic psuA, pvuA, and psuA-pvuA double-deletion mutants followed by complementation of the double-deletion mutant with psuA or pvuA was used to identify psuA as a gene encoding an OMP involved in the uptake of ferric VF. Thus, psuA and pvuA were renamed pvuA1 and pvuA2, respectively. Moreover, we clarified the TonB specificities of PvuA1 and PvuA2, because V. parahaemolyticus has three sets of the TonB systems. The triple deletion of pvuA1, tonB1, and tonB2, and the double deletion of pvuA2 and tonB2 resulted in the complete loss of growth promotion by VF. This finding indicates that the energy required for PvuA1 and PvuA2 to transport ferric VF across the outer membrane is provided by the TonB2 system and by both the TonB1 and TonB2 systems, respectively. PMID- 22092767 TI - Proteomics and multilocus sequence analysis confirm intraspecific variability of Vibrio tapetis. AB - Vibrio tapetis is the etiological agent of brown ring disease (BRD) in clams. Phenotypic, antigenic and genetic variability have been demonstrated, with three groups being established associated with host origin. In this work we analyze the variability of representative strains of these three groups, CECT 4600(T) and GR0202RD, isolated from Manila clam and carpet-shell clam, respectively, and HH6087, isolated from halibut, on the basis of the whole proteome analysis by 2D PAGE and multilocus sequence analysis (MLSA). A quantitative analysis of the proteome match coefficient showed a similarity of 79% between the clam isolates, whereas fish isolate showed similarities lower than 70%. A preliminary mass spectrometry (MS) assay allowed the identification of 27 proteins including 50S ribosomal protein L9, riboflavin synthase beta subunit, ribose-phosphate pyrophosphokinase and succinyl-CoA synthase alpha subunit. The MLSA approach gave similar results, showing a 99.4% similarity of the clam isolates, which was higher than that observed between the fish isolate and either clam strain (98.2%). The topology of the maximum parsimony tree, obtained from 2D-PAGE analysis, and the phylogenetic tree, constructed with the maximum likelihood algorithm from concatenated sequences of 16S rRNA gene and five housekeeping genes (atpA, pyrH, recA, rpoA and rpoD), was very similar, confirming the closer relationship between the two clam isolates. PMID- 22092768 TI - Influence of bone augmentation procedures on the short-term prognosis of simultaneously placed implants. AB - OBJECTIVES: The purpose of this study was to investigate the effect of simultaneous bone-augmentation procedures, and their combination, on the survival of dental implants and on the incidence of complications. MATERIAL AND METHODS: Within a retrospective analysis, 958 implants placed in 404 patients (mean age 58.18) were selected from a prospective clinical study. In 304 cases of reduced bone width, bone spreading (n = 217) with hand osteotomes, or bone splitting (n = 15), or guided bone regeneration (n = 72) combined with autogenous bone grafts were also performed. Eighty-eight implants were placed in combination with simultaneous internal sinus floor elevation without using graft material. For 194 additional implants, several augmentation procedures were combined because of extensive bone deficits. Three-hundred and seventy-two conventionally placed implants served as controls. Implant failures and complications were recorded after a mean observation period of 2.1 years (maximum 6.9 years). RESULTS: Seventeen failures and nine additional implant-related complications were observed. After 4 years, Kaplan-Meier curves revealed a probability of survival without complication of 97.5% for conventionally placed implants, and 95.8% for implants placed in combination with a single augmentation technique. If several augmentation techniques were combined, success decreased to 94.1%. Complication free survival differences between combined augmentation techniques and conventionally placed implants were significant (P = 0.004). Age, gender, and location showed no effect on implant survival. CONCLUSIONS: It can be concluded that simultaneous bone-augmentation techniques slightly reduce short-term prognosis for dental implants. This effect was more pronounced when advanced defects required the combination of several augmentation procedures. PMID- 22092769 TI - Role of teeth adjacent to implants installed immediately into extraction sockets: an experimental study in the dog. AB - AIM: To evaluate the influence of the presence of both adjacent teeth on the level of alveolar bony crest at sites where implants were installed into the socket immediately after tooth extraction. MATERIAL AND METHODS: Six Labrador dogs were used. Extractions of all teeth from the second premolar to the first molar were performed in the right side of the mandible, after full-thickness flap elevation. In the left side of the mandible, an endodontic treatment of the mesial root of the third and fourth premolars was performed. Full-thickness flaps were elevated, the teeth hemi-sected, and the distal roots removed. Immediately after, implants were bilaterally installed with the margin flush to the buccal bony crest. The implants were placed in the center of the alveolus at the third premolars and toward the lingual bony plate of the alveolus at the fourth premolars. After 3 months of healing, the animals were euthanized. RESULTS: All implants were integrated in mature bone. More bone resorption was observed at the test compared to the control sites. At the buccal aspect, a resorption of 2.8 +/- 0.5 and 1.6 +/- 0.4 mm at the third premolars and of 2.4 +/- 0.6 and 0.8 +/- 0.7 mm at the fourth premolars were found, at the test and control sites, respectively. At the lingual aspect, the bony crest was apically located in relation to the implant shoulder 1.5 +/- 0.3 and 0.5 +/- 0.5 mm at the third premolars and 1.6 +/- 0.6 and 0.3 +/- 1.1 mm at the fourth premolars, at the test and control sites, respectively. A lower buccal bone resorption was found at the control implants placed lingually. CONCLUSION: Multiple extractions of teeth adjacent to a socket into which implants were installed immediately after, tooth extraction induced more alveolar bone recession compared to sites where the adjacent teeth were preserved. Moreover, an implant placed more lingually yielded less recession of the buccal aspect of the implant. PMID- 22092770 TI - Novel protein identification methods for biomarker discovery via a proteomic analysis of periodontally healthy and diseased gingival crevicular fluid samples. AB - AIM: To identify possible novel biomarkers in gingival crevicular fluid (GCF) samples from chronic periodontitis (CP) and periodontally healthy individuals using high-throughput proteomic analysis. MATERIALS AND METHODS: Gingival crevicular fluid samples were collected from 12 CP and 12 periodontally healthy subjects. Samples were trypically digested with trypsin, eluted using high performance liquid chromatography, and fragmented using tandem mass spectrometry (MS/MS). MS/MS spectra were analysed using PILOT_PROTEIN to identify all unmodified proteins within the samples. RESULTS: Using the database derived from Homo sapiens taxonomy and all bacterial taxonomies, 432 human (120 new) and 30 bacterial proteins were identified. The human proteins, angiotensinogen, clusterin and thymidine phosphorylase were identified as biomarker candidates based on their high-scoring only in samples from periodontal health. Similarly, neutrophil defensin-1, carbonic anhydrase-1 and elongation factor-1 gamma were associated with CP. Candidate bacterial biomarkers include 33 kDa chaperonin, iron uptake protein A2 and phosphoenolpyruvate carboxylase (health-associated) and ribulose biphosphate carboxylase, a probable succinyl-CoA:3-ketoacid-coenzyme A transferase, or DNA-directed RNA polymerase subunit beta (CP-associated). Most of these human and bacterial proteins have not been previously evaluated as biomarkers of periodontal conditions and require further investigation. CONCLUSIONS: The proposed methods for large-scale comprehensive proteomic analysis may lead to the identification of novel biomarkers of periodontal health or disease. PMID- 22092771 TI - Surgical treatment of nail apparatus melanoma in situ: the use of artificial dermis in reconstruction. PMID- 22092772 TI - Targeted 307 nm UVB-phototherapy in psoriasis. A pilot study comparing a 307 nm excimer light with topical dithranol. AB - BACKGROUND: Phototherapy is a cornerstone in treatment of moderate-to-severe psoriasis. Narrow-band UVB has been shown to be a potent therapeutic tool. To reduce the potential carcinogenic risk, targeted phototherapy has been developed using excimer lasers or excimer light devices (ELD). OBJECTIVE: The role of excimer light therapy in practice and modes of action are not completely understood. We wanted to investigate a 307 nm ELD for plaque psoriasis in comparison with topical dithranol therapy twice daily. METHODS: We conducted a pilot trial in 21 adult patients with moderate plaque-type psoriasis. Two target lesions of comparable size and plaque-modified Psoriasis Activity and Severity Index (PSI) scores were selected. Lesion A was treated three times using a newly developed 307 nm ELD. Lesion B was treated twice daily with dithranol ointment. The mean period of treatment was 9 days. Clinical evaluation included PSI scores, safety, time needed to treat, and patient's satisfaction. In addition, fluorescence-remission imaging technique was used for objective evaluation. RESULTS: Both treatments improved the PSI score (mean 3.0 points). The treatments were safe but ELD was more convenient for patients. The time needed to treat the target lesion was significantly shorter with ELD. Targeted UVB therapy normalized NADH fluorescence in lesional skin. CONCLUSIONS: The 307 nm excimer light therapy for plaque type psoriasis was equipotent to twice daily topical dithranol. Efficacy, safety, and convenience suggest that targeted UVB therapy with quasi monochromatic light is a new useful treatment option for patients with limited psoriatic plaques. PMID- 22092773 TI - The effect of abutment dis/reconnections on peri-implant bone resorption: a radiologic study of platform-switched and non-platform-switched implants placed in animals. AB - OBJECTIVES: The purpose of this animal study was to radiologically measure the influence of abutment disconnection on bone resorption and to compare this influence on platform-switched vs. non-platform-switched implants. METHODS: The study design included extraction of all mandibular premolars in five canines . After 2 months, six implants were placed in each dog. Four of them were platform switched (PS) implants and two were non-platform-switched (NPS) implants. Some or all of the abutments connected to the implants were disconnected at pre-ordained post-surgical intervals. Radiographs were taken at the time of implant placement and at every handling. The values for mesial (horizontal and vertical) and distal (horizontal and vertical) bone resorption were taken and compared for each implant at every abutment dis/reconnection. RESULTS: The average vertical bone resorption around NPS implants after four dis/reconnections was 1.09 mm (SD 0.25 mm), and the average horizontal bone resorption was 0.98 mm (SD 0.27 mm). The average vertical bone resorption around PS implants after four dis/reconnections was 0.24 mm, (SD 0.08 mm) and the average horizontal bone resorption was 0.24 mm (SD 0.13 mm). The difference of the average horizontal and vertical bone resorption around NPS (site D) and PS (site A) implants was statically significant (P < 0.05). The average mesial and distal bone resorption values around PS (site A) implant adjacent to a tooth were compared, and statically significant differences were found (P < 0.05). CONCLUSIONS: Implants with a PS design show less peri-implant bone resorption during the healing process and as their abutments are disconnected, than do comparably dis/reconnected NPS implants. The location of the PS implant next to a tooth may decrease radiographically visible peri-implant bone resorption significantly. PMID- 22092774 TI - Are reptile and amphibian species younger in the Northern Hemisphere than in the Southern Hemisphere? AB - A previous analysis of molecular phylogenies suggested that intraspecific diversification had occurred more recently in temperate-zone Northern Hemisphere reptiles and amphibians than in Southern Hemisphere taxa. Here, we test potential explanations for this pattern. We examined published phylogenetic analyses, derived from genetic sequence data, to generate two estimates of the age of species: (i) the oldest intraspecific diversification event within each taxon and (ii) the inferred timing of the split between two sister species. The timing of splits between species shows the same pattern as splits within species, and thus may be due to climatically driven cladogenic and extinction events or may be an artefact of differing levels of taxonomic knowledge about the fauna. Current rates of species descriptions suggest that many more taxa remain to be described in the Southern Hemisphere than the Northern Hemisphere; for that bias to fully explain our results on species age differences, the proportion of undescribed Southern taxa would need to be >= 12% in reptiles and >= 51% in anurans. For reptiles, taxonomic ignorance plausibly explains the apparent difference in mean age of species between the Southern and Northern Hemispheres; but this explanation can apply to amphibians only if a vast number of Southern taxa remain to be described. PMID- 22092775 TI - Grey eosinophils in sighthounds: frequency in 3 breeds and comparison of eosinophil counts determined manually and with 2 hematology analyzers. AB - BACKGROUND: Grey eosinophils (GE) reported to occur in Greyhounds, and occasionally in other breeds, have clear granules, probably due to abnormal staining properties. OBJECTIVES: The aims of this study were to investigate the frequency of GE in Greyhounds and 2 other sighthound breeds, and to assess the capacity of the ADVIA 120 and Sysmex XT-2000iV hematology analyzers to correctly identify GE. METHODS: Blood samples from 20 Greyhounds, 29 Italian Greyhounds, and 24 Whippets were analyzed using the ADVIA and Sysmex hematology analyzers, and blood smears stained with May-Grunwald Giemsa were evaluated microscopically. The frequency of samples with GE detected on smears was recorded for each breed. Manual and automated eosinophil counts were compared using a Wilcoxon signed-rank test. Agreement between methods was assessed using Passing-Bablok and Bland Altman plots. RESULTS: GE were detected in all 3 breeds: 9/20 Greyhounds (45.0%), 10/29 Italian Greyhounds (34.5%), and 5/24 Whippets (62.5%) with no significant differences in the frequency of GE among the breeds. In samples containing GE, both analyzers underestimated the percentage of eosinophils and occasionally eosinophils were not detected at all. When a novel "GE gate" was used, the percentage of eosinophils reported by the Sysmex was similar to that obtained by manual counting. CONCLUSIONS: GE are found in the blood of sighthounds other than Greyhounds. Hematology analyzers may underestimate the percentage of GE, probably due to their abnormal physical or chemical features. Underestimation is slight and usually clinically insignificant, but occasionally eosinophils are completely misclassified. Using the Sysmex analyzer, a GE gate can be designed to normalize the eosinophil count. PMID- 22092776 TI - Characterization of the fecal bacteria communities of forage-fed horses by pyrosequencing of 16S rRNA V4 gene amplicons. AB - The diversity of the equine fecal bacterial community was evaluated using pyrosequencing of 16S rRNA gene amplicons. Fecal samples were obtained from horses fed cool-season grass hay. Fecal bacteria were characterized by amplifying the V4 region of bacterial 16S rRNA gene. Of 5898 mean unique sequences, a mean of 1510 operational taxonomic units were identified in the four fecal samples. Equine fecal bacterial richness was higher than that reported in humans, but lower than that reported in either cattle feces or soil. Bacterial classified sequences were assigned to 16 phyla, of which 10 were present in all samples. The largest number of reads belonged to Firmicutes (43.7% of total bacterial sequences), Verrucomicrobia (4.1%), Proteobacteria (3.8%), and Bacteroidetes (3.7%). The less abundant Actinobacteria, Cyanobacteria, and TM7 phyla presented here have not been previously described in the gut contents or feces of horses. Unclassified sequences represented 38.1% of total bacterial sequences; therefore, the equine fecal microbiome diversity is likely greater than that described. This is the first study to characterize the fecal bacterial community in horses by the use of 16S rRNA gene amplicon pyrosequencing, expanding our knowledge of the fecal microbiota of forage-fed horses. PMID- 22092777 TI - Impact of fatigue on performance in registered nurses: data mining and implications for practice. AB - Performance of nurses has a direct effect on the quality and safety of care that is delivered. Fatigue has been identified as a factor that leads to performance decrements in healthcare workers, especially nurses. Determining associations between dimensions of fatigue and performance is imperative to better understanding fatigue in nurses and the potential implications for both patient and provider safety. This article identifies associations between ranges of fatigue levels and significant differences in perceived performance, and analyzes interactions between fatigue dimensions in relation to perceived performance scores. Overall, mental fatigue tended to have higher perceived performance decrements than physical and total fatigue in the highest fatigue ranges. As physical fatigue begins to develop in nurses, physical exertion rather than discomfort is more critical to perceived performance. As acute fatigue levels increase, perceived performance levels continue to decrease, whereas the role of chronic fatigue is relatively constant. Minimizing the development of acute fatigue may help in maintaining higher performance levels. The findings from this study provide valuable information in quantifying the changes in perceived performance with regard to specific fatigue levels, as well as an initial understanding of how the individual dimensions and states of fatigue vary in their association with perceived performance decrements. PMID- 22092778 TI - Gateway to doping? Supplement use in the context of preferred competitive situations, doping attitude, beliefs, and norms. AB - Nutritional supplement (NS) use is widespread in sport. This study applied an integrated social cognitive approach to examine doping attitudes, beliefs, and self-reported doping use behavior across NS users (n = 96) and nonusers (n = 116). Following ethical approval, 212 competitive athletes (age mean = 21.4, s = 4.5; 137 males) completed self-reported measures of doping-related social cognitions and behaviors, presented in an online format where completion implied consent. Significantly more NS users (22.9%) reported doping compared with nonusers (6.0%; U = 4628.0, P < 0.05). NS users presented significantly more positive attitudes toward doping (U = 3152.0, P < 0.05) and expressed a significantly greater belief that doping is effective (U = 3152.0, P < 0.05). When presented with the scenario that performance-enhancing substances are effective and increase the possibility of winning, NS users were significantly more in favor of competing in situations that allow doping (U = 3504.5, P < 0.05). In sum, doping use is three-and-a-half times more prevalent in NS users compared with nonusers. This finding is accompanied by significant differences in doping attitudes, norms, and beliefs. Thus, this article offers support for the gateway hypothesis; athletes who engage in legal performance enhancement practices appear to embody an "at-risk" group for transition toward doping. Education should be appropriately targeted. PMID- 22092779 TI - Results of drug hypersensitivity evaluations in a large group of children and adults. AB - BACKGROUND: Proven IgE or T-cell mediated drug hypersensitivity reactions (DHRs) seem less common in children compared with adults. However, this has never been proved by data. OBJECTIVE: To determine and compare proven DHR prevalence in children and adults. METHODS: Using the DAHD (Drug Allergy and Hypersensitivity Database) cohort, children with proven DHRs were compared with adults. The international EAACI-ENDA recommendations were followed. Patients were divided into four groups: index reaction and test during childhood (C/C), index reaction at childhood and test at adulthood (C/A), index reactions at childhood and adulthood and test at adulthood (CA/A), index reaction and test at adulthood (A/A). RESULTS: A total of 3275 patients (67.9% female), comprising a total of 4370 patient-episodes, were evaluated (74.5% belonged to the A/A group). Prevalence of positive tests was 15.2% (95%CI, 14.1-16.2) for all tested classes, 10.6% (8.3-13.0) for C/C, 10.6% (7.5-13.6) for C/A, 22.1% (12.8-31.3) for CA/A and 16.5% (15.2-17.8) for A/A. The prevalence was lower in group C/C compared with groups A/A (P < 0.0001) and CA/A (P = 0.003). It was also lower in group C/A compared with the two latter groups (respectively P = 0.003 and P = 0.005). Significant differences were found for maculopapular exanthemas only, and not for urticaria/angioedema and anaphylaxis. The difference was mainly observed with beta-lactams and not for NSAIDs. CONCLUSION AND CLINICAL RELEVANCE: Suspicions of DHRs are less likely to be confirmed in children. PMID- 22092780 TI - Tensegrity and plasma for skin regeneration. AB - BACKGROUND: Mechanical stresses induce variations in tissue tensegrity leading to cell proliferation and differentiation thus contributing to tissue remodelling. Besides mechanical forces, skin remodelling may be induced by the application of plasma, a new type of energy delivery resulting in controlled heat damage. Here we demonstrate that mechanical stress induced by the application of vacuum increases the efficacy of plasma in skin regeneration treatment. METHODS: Vacuum alone and vacuum plus plasma at different energies were applied to rat skin and biopsies collected at different time intervals after treatments. Skin integrity, collagen arrangement, inflammation and myofibroblast differentiation were assessed by Masson's trichrome staining. Procollagen synthesis was evaluated by immunohistochemistry. RESULTS: Vacuum alone induced significant and temporary alterations in the distribution of collagen bundles, with concomitant procollagen synthesis in the dermis; no myofibroblasts and no signs of inflammation were observed. Vacuum plus plasma determined an important spatial modification of collagen bundles, more intense than vacuum or plasma alone. Significant increase of procollagen synthesis, numerous myofibroblasts but slight sign of inflammation appeared after the treatment. CONCLUSION: Vacuum mechanically stimulated fibroblasts, producing changes in collagen arrangement and procollagen synthesis. Plasma led to the same effects through thermal damage. Application of a combined treatment consisting in vacuum plus plasma induced more remarkable effects on skin regeneration with relatively low plasma energies and no relevant side effects. PMID- 22092781 TI - Management of severe anogenital acne inversa (hidradenitis suppurativa). AB - BACKGROUND: Severe anogenital acne inversa (AI) is a debilitating chronic inflammatory disease with a major negative effect on quality of life. OBJECTIVES: To evaluate the role of surgery in the treatment of severe anogenital AI. METHODS: We analyzed the records of patients with anogenital AI from 2000 to 2010. Assessment was done using the Hidradenitis Suppurativa Lesion, Area, and Severity Index (HS-LASI), pain visual analogue scale, physician global assessment (PhGA), and patient global assessment (PaGA). Comorbidities and adverse events were analyzed. RESULTS: Sixty-seven patients with a Hurley score of 3 were identified. Mean follow-up was 56.9 +/- 41.3 months. A number of comorbidities were observed. After surgery, mean pain scores decreased from 6.3 +/- 1.5 to 0.8 +/- 0.7, PhGA improved from 6.8 +/- 1.2 to 0.9 +/- 0.6, PaGA improved from 7.3 +/ 1.2 to 1.1 +/- 0.5, and HS-LASI decreased from 41.8 +/- 21.3 to 2.4 +/- 2.8. Adverse reactions were seen in 10.4%. The total relapse rate was 6% (5 patients) with only one case with healing by secondary intention (2% of 49 patients). CONCLUSIONS: Surgery is the cornerstone of treatment for advanced AI. Healing by secondary intention results in significant reduction of complaints and achieves satisfying body contouring. PMID- 22092782 TI - Influence of aerobic cycle exercise training on patellar tendon cross-sectional area in older women. AB - Nine to 12 weeks of resistance exercise training in young individuals induces quadriceps muscle (~6%) and region-specific patellar tendon (4-6%) hypertrophy. However, 12 weeks of resistance exercise training (~1 h total exercise time) in older individuals (60-78 years) induces quadriceps muscle hypertrophy (9%) without impacting patellar tendon size. The current study examined if a different loading paradigm using cycle exercise would promote patellar tendon hypertrophy or alter the internal tendon properties, measured with magnetic resonance imaging signal intensity, in older individuals. Nine women (70 +/- 2 years) completed 12 weeks of aerobic upright cycle exercise training (~28 h total exercise time). Aerobic exercise training increased (P < 0.05) quadriceps muscle size (11 +/- 2%) and VO2max (30 +/- 9%). Mean patellar tendon cross-sectional area (CSA) (2 +/- 1%) and signal intensity (-1 +/- 2%) were unchanged (P > 0.05) over the 12 weeks of training. Region-specific CSA was unchanged (P > 0.05) at the proximal (-1 +/- 3%) and mid regions (2 +/- 2%) of the tendon but tended (P = 0.069) to increase at the distal region (5 +/- 3%). Region-specific signal intensity differed along the tendon but was unchanged (P > 0.05) with training. Although more studies are needed, exercise-induced patellar tendon hypertrophy, compared with skeletal muscle, appears to be attenuated in older individuals, while the loading pattern associated with aerobic exercise seems to have more impact than resistance exercise in promoting patellar tendon hypertrophy. PMID- 22092783 TI - Upper cutaneous lip reconstruction after tumor excision. PMID- 22092784 TI - Acellular dermal matrix allograft versus subepithelial connective tissue graft in treatment of gingival recessions: a 5-year randomized clinical study. AB - AIM: The present randomized clinical trial compared the long-term results of subepithelial connective tissue graft (SCTG) versus acellular dermal matrix allograft (ADMA) in treatment of gingival recessions. MATERIALS AND METHODS: In 16 patients with bilateral Miller Class I/II gingival recessions, one side was treated with SCTG and the other side with ADMA. Clinical parameters were measured at baseline, 6 months, and at 5 years post-surgery. RESULTS: Fifteen patients completed the study. At 6 months, all parameters showed significant improvement in ADMA and SCTG groups [complete root coverage (CRC): 73.3% versus 26.7%, p = 0.027; reduction of recession depth (RD): 2.6 +/- 1.1 mm versus 2.2 +/- 1.1 mm, p = 0.376; reduction of recession width (RW): 3.0 +/- 1.4 mm versus 2.4 +/- 1.4 mm, p = 0.207 respectively]. At 5 years, significant relapses were detected in CRC and reduction of RD and RW in both groups with no statistically significant difference (CRC: 20.0% versus 13.3%, p = 1.00; RD: 1.6 +/- 1.2 mm versus 1.5 +/- 1.4mm, p = 0.838; RW: 1.8 +/- 1.4 mm versus 1.3 +/- 1.5mm, p = 0.367). Patients practicing horizontal toothbrushing habit showed more relapse (OR = 11.2; p = 0.01). Compared with baseline, the gingival width (GW) did not increase in ADMA treated sites (p = 0.903). CONCLUSION: Five-year results of SCTG and ADMA were similar in terms of CRC and reduction of RD and RW. Both techniques showed a significant relapse associated with returning to horizontal toothbrushing habit. Increase of GW was stable in SCTG-treated sites, but reached to pre-surgical values in ADMA-treated cases. PMID- 22092785 TI - Emotional contagion of dental fear to children: the fathers' mediating role in parental transfer of fear. AB - BACKGROUND: Dental fear is considered to be one of the most frequent problems in paediatric dentistry. According to literature, parents' levels of dental fear play a key role in the development of child's dental anxiety. HYPOTHESIS OR AIM: We have tried to identify the presence of emotional transmission of dental fear among family members and to analyse the different roles that mothers and fathers might play concerning the contagion of dental fear to children. We have hypothesized a key role of the father in the transfer of dental fear from mother to child. DESIGN: A questionnaire-based survey (Children's Fear Survey Schedule Dental Subscale) has been distributed among 183 schoolchildren and their parents in Madrid (Spain). Inferential statistical analyses, i.e. correlation and hierarchical multiple regression, were carried out and possible mediating effects between variables have been tested. RESULTS: Our results support the hypothesis that family members' levels of dental fear are significantly correlated, and they also allow us to affirm that fathers' dental fear is a mediating variable in the relationship between mothers and children's fear scores. CONCLUSIONS: Together with the presence of emotional transmission of dental fear among family members, we identified the relevant role that fathers play as regards the transfer of dental fear from parents to children. PMID- 22092786 TI - Staphylococcal-derived superantigen enhances peanut induced Th2 responses in the skin. AB - BACKGROUND: The allergen-induced activation and expansion of IL-4 producing T helper type 2 (Th2) cells is a key event in the initiation and progression of allergic disease. Intriguingly, concomitant early childhood staphylococcal skin infections are being increasingly implicated in the allergen-induced switch of primary T cell responses towards the Th2 phenotype. OBJECTIVE: We sought to identify whether or not staphylococcal-derived superantigen can influence the primary T cell response in the skin to food allergens with a view to determining whether such exposures create the immune pathology that predisposes to the development of food allergy. METHODS: Using a novel Th2 reporter model, we determined the ability of the staphylococcal superantigen (SEB) to influence priming in the skin of IL-4 expressing Th2 cells by peanut extract (PE). Factors including the effect of SEB on the magnitude of the Th2 response in the skin draining lymph nodes, T cell receptor V region usage and the influence of endotoxin were evaluated. RESULTS: Primary exposure to PE and SEB lead to significantly enhanced PE specific Th2 responses when the mice were subsequently exposed to PE alone. The enhancement of the Th2 response was dependent on the Vbeta-binding properties of the SEB, but was not affected by endotoxin-mediated TLR-4 effects or strain differences in the mice. CONCLUSIONS AND CLINICAL RELEVANCE: These results identify that in the skin environment, the presence of SEB can significantly increase the numbers of allergen-induced Th2 cells which develop in response to subsequent allergen exposure. These data highlight the process by which individuals may become pathologically sensitized to food allergens in early life. PMID- 22092787 TI - Sulfidogenesis in hypersaline chloride-sulfate lakes of Kulunda Steppe (Altai, Russia). AB - The activity and culturable diversity of sulfidogens were investigated in anoxic sediments of four hypersaline lakes with pH 7.6-8.2 in the Kulunda Steppe (Altai, Russia). Sulfate reduction rates were low, varying from 0.1 to 6.0 nmol HS(-) /(cm(3) h) with a maximum in the top 10 cm layer. Potential sulfidogenic rates with thiosulfate and sulfur as the e-acceptors were higher than with sulfate and were stimulated by formate, lactate, and acetate. Sulfidogenesis was optimal at salt concentrations below 2 M NaCl. Cultivation at 2 M NaCl resulted in the isolation of several strains of moderately halophilic SRB, but no growth of SRB was observed at 4 M NaCl. At lithotrophic conditions (i.e., with formate or H(2) as e-donors), several closely related alkalitolerant strains belonging to the genus Desulfonatronovibrio were isolated. Enrichments at heterotrophic conditions with lactate, propionate, acetate, or butyrate using sulfate or thiosulfate as e acceptors yielded isolates related to Desulfosalsimonas propionicica, Desulfohalobium utahense, and Desulfocella halophila. Sulfur-reducing enrichments at 2 M NaCl with ethanol produced a member of the genus Halanaerobium, while enrichments at 4 M NaCl with acetate were dominated by archaea, demonstrating for the first time such type of catabolism in haloarchaea. PMID- 22092788 TI - Effects of platelet-rich and -poor plasma on the reparative response of gingival fibroblasts. AB - OBJECTIVES: Although platelet-rich plasma (PRP) has been proposed as a therapeutic tool to enhance wound repair, the cellular and molecular mechanisms stimulated by this agent are still not completely understood. The present study was designed to characterize the effects of PRP and platelet-poor plasma (PPP) supernatants on cell responses involved in gingival tissue repair. METHODS: We studied the response of human gingival fibroblasts (HGF) to PRP and PPP fractions on: matrix contraction, cell migration, myofibroblastic differentiation, production of matrix components and proteolytic enzymes. PRP and PPP were obtained from donors using a commercial kit. Matrix contraction was evaluated by means of collagen lattices in the presence of matrix metalloproteinase (MMP) and actin polymerization inhibitors. The production of matrix molecules and proteinases was assessed through Western-blot. RhoA activity was evaluated through a pull-down assay. Actin distribution and focal adhesions were assessed through immunofluorescence. Transforming growth factor-beta (TGF-beta) was quantified through ELISA. RESULTS: Both PRP and PPP stimulated human gingival fibroblasts-populated collagen gel contraction and Ilomastat and cytochalasin D inhibited this response. PRP and PPP also stimulated MT1-MMP and TIMP-2 production, RhoA activation and actin cytoskeleton remodeling, cell migration/invasion and myofibroblastic differentiation. TGF-beta1 was found at significantly higher concentrations in PRP than in PPP. CONCLUSIONS: Both PRP and PPP promote wound tissue remodeling and contraction through the stimulation of actin remodeling, the activity of MMPs, promotion of cell migration, and myofibroblastic differentiation. The similar biological responses induced by PRP and PPP suggest that both platelet-derived fractions may exert a positive effect on gingival repair. PMID- 22092789 TI - Stenotrophomonas interspecies differentiation and identification by gyrB sequence analysis. AB - Stenotrophomonas species are found commonly in environmental and clinical samples; Stenotrophomonas maltophilia is an important opportunistic pathogen of humans. Traditional phenotyping protocols, as well as genotyping by 16S rRNA gene sequence analysis, do not reliably distinguish the species of Stenotrophomonas. Sequence analyses of two targeted PCR-amplified regions of the gyrB gene, which encodes the beta-subunit of DNA gyrase, enabled resolution and identification of these species. Most type strains of the different species of Stenotrophomonas exhibited more than 7% dissimilarity in the gyrB gene sequences. Among these, strains identified as the same species exhibited sequence dissimilarities up to 4.6% and 5.9% for the two regions, respectively. Strains identified as S. maltophilia, with 16S rRNA gene sequence similarities > 99.0%, were grouped within a 'S. maltophilia complex'; these organisms exhibited gyrB similarities as low as 93%. Many of these strains possessed genomic DNA similarities with the type strain of S. maltophilia CCUG 5866(T) below 70%. These data, including gyrB sequence comparisons, indicate that strains identified as S. maltophilia may comprise distinct, new species. PMID- 22092790 TI - Wound microbiology: tabula rosa, a blank slate. PMID- 22092791 TI - The importance of a multifaceted approach to characterizing the microbial flora of chronic wounds. AB - Chronic wounds contain complex polymicrobial communities of sessile organisms that have been underappreciated because of limitations of standard culture techniques. The aim of this work was to combine recently developed next generation investigative techniques to comprehensively describe the microbial characteristics of chronic wounds. Tissue samples were obtained from 15 patients with chronic wounds presenting to the Johns Hopkins Wound Center. Standard bacteriological cultures demonstrated an average of three common bacterial species in wound samples. By contrast, high-throughput pyrosequencing revealed increased bacterial diversity with an average of 17 genera in each wound. Data from microbial community profiling of chronic wounds were compared with published sequenced analyses of bacteria from normal skin. Increased proportions of anaerobes, Gram-negative rods and Gram-positive cocci were found in chronic wounds. In addition, chronic wounds had significantly lower populations of Propionibacterium compared with normal skin. Using epifluorescence microscopy, wound bacteria were visualized in highly organized thick confluent biofilms or as scattered individual bacterial cells. Fluorescent in situ hybridization allowed for the visualization of Staphylococcus aureus cells in a wound sample. Quorum sensing molecules were measured by bioassay to evaluate signaling patterns among bacteria in the wounds. A range of autoinducer-2 activities was detected in the wound samples. Collectively, these data provide new insights into the identity, organization, and behavior of bacteria in chronic wounds. Such information may provide important clues to effective future strategies in wound healing. PMID- 22092792 TI - Clinical efficacy of basic fibroblast growth factor on pressure ulcers: case control pairing study using a new evaluation method. AB - A basic fibroblast growth factor (bFGF) case and a control case whose total scores of Pressure Ulcer Healing Process-Ohura (PUHP-Ohura) and risk factors for pressure ulcers, and level of care for pressure ulcers were equivalent were paired. Twenty-three such eligible pairs were enrolled in this study. Both cases in each pair were treated under conditions in which extrinsic factors such as the use of a pressure-relief mattress and the frequency of postural change were equivalent. The efficacy of bFGF was assessed by analyzing the data obtained over time as the scores of PUHP-Ohura for nine observation items using the SAS MIXED procedure. Treatment of pressure ulcers with bFGF accelerated wound healing over time more significantly than the control in six observation items (exudate volume, ulcer depth, granulation formation, wound edge, epithelialization, total score of the PUHP-Ohura). These data suggest that it may be possible to evaluate drugs for the treatment of pressure ulcers using the PUHP-Ohura wound-assessment tool. PMID- 22092793 TI - Prevalence rate for inherited thrombophilia in patients with chronic and recurrent venous leg ulceration. AB - The aim of the study was to determine the prevalence rate for inherited thrombophilia (IT) in patients with chronic (CVU) and recurrent venous leg ulceration. We also investigated and evaluated the severity of the clinical pattern of CVU in patients with and without IT. We examined 110 patients with CVU (the study group) and 110 healthy subjects (the control group). We prepared a questionnaire to be completed by each study participant. Ultrasound Doppler color imaging or/and duplex ultrasonography was performed to evaluate the efficiency of the venous system. The ankle-brachial index was calculated to determine the efficiency of the arterial system. We examined both groups for the presence of IT. IT was diagnosed in 30% of study group and in 1.8% of control group. Our diagnoses of deep vein thrombosis (DVT) were based on medical interviews, physical examinations, and an ultrasonography of the venous system and concerned 64 study group patients (58.2%), 35 of whom (31.8%) experienced recurrent DVT. Proximal and/or distal DVT was determined in an interview and/or by an ultrasonography performed for all patients with CVU and IT. In 94% of these patients, DVT was recurrent, and in 88% of patients with CVU and IT, we observed recurrent DVT and CVU. It recurred more often and persisted longer when compared to patients with CVU and no IT, despite similar management. No differences were observed in ulcer size, localization, or pain level related to ulceration between patients with CVU and IT and those with CVU and no IT. PMID- 22092794 TI - Clinical wound assessment using DESIGN-R total score can predict pressure ulcer healing: pooled analysis from two multicenter cohort studies. AB - There are few clinical tools with both predictive validity for pressure ulcer healing and availability in broad populations. We evaluated whether the total scores from DESIGN-R tool could predict pressure ulcer healing. We followed 3,196 patients with pressure ulcers from two multicenter cohort studies until wound healing, patient death, or discharge. Wound severity was evaluated by DESIGN-R tool from 0 (healed) to 66 (greatest severity). In the multivariate Cox proportional hazard model, higher DESIGN-R total scores at baseline were associated with lower healing rates (hazard ratio 0.90, 95% confidence interval 0.89-0.92), independent of the patient's characteristics, setting types, and wound depth or location. DESIGN-R had discriminative value for wound healing up to 90 days; the area under the receiver-operating characteristics curve from univariate analysis was 0.81 for healing within 30 days and 0.74 for healing within 30-90 days. The cutoff points were 9 for healing within 30 days and 18 within 30-90 days (positive and negative predictive value 78.8 and 74.1%; 63.9 and 81.1%, respectively). These points were validated for both superficial and deep ulcers. DESIGN-R can be a useful tool to predict pressure ulcer healing for a wide range of patient populations, settings, and wound locations. PMID- 22092795 TI - Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 in the formation of postburn hypertrophic scar (HTS). AB - Recent data support the involvement of stromal cell-derived factor 1 (SDF-1) in the homing of bone marrow-derived stem cells to wound sites during skeletal, myocardial, vascular, lung, and skin wound repair as well as some fibrotic disorders via its receptor CXCR4. In this study, the role of SDF-1/CXCR4 signaling in the formation of hypertrophic scar (HTS) following burn injury and after treatment with systemic interferon alpha2b (IFNalpha2b) is investigated. Studies show SDF-1/CXCR4 signaling was up-regulated in burn patients, including SDF-1 level in HTS tissue and serum as well as CD14+ CXCR4+ cells in the peripheral blood mononuclear cells. In vitro, dermal fibroblasts constitutively expressed SDF-1 and deep dermal fibroblasts expressed more SDF-1 than superficial fibroblasts. Lipopolysaccharide increased SDF-1 gene expression in fibroblasts. Also, recombinant SDF-1 and lipopolysaccharide stimulated fibroblast-conditioned medium up-regulated peripheral blood mononuclear cell mobility. In the burn patients with HTS who received subcutaneous IFNalpha2b treatment, increased SDF 1/CXCR4 signaling was found prior to treatment which was down-regulated after IFNalpha2b administration, coincident with enhanced remodeling of their HTS. Our results suggest that SDF-1/CXCR4 signaling is involved in the development of HTS by promoting migration of activated CD14+ CXCR4+ cells from the bloodstream to wound sites, where they may differentiate into fibrocyte and myofibroblasts and contribute to the development of HTS. PMID- 22092796 TI - Aminated beta-1,3-D-glucan has a dose-dependent effect on wound healing in diabetic db/db mice. AB - Inflammatory responses are common in diabetes and are operative in angiopathy, neuropathy, and wound healing. There are indications of incomplete macrophage activation in diabetes and reduced expression of growth factors. We have previously found that up to 15 topical applications of the macrophage-stimulant, aminated beta-1,3-D-glucan (AG), improved wound healing in db/db mice. The present open-label study was undertaken to examine dose-dependent effects of AG over 40 days in db/db mice. AG was given as a single dose (group 1), one dose every 10th day (group 2), five initial doses on consecutive days (group 3), and >=15 doses (group 4). Controls were db/db mice receiving platelet-derived growth factor + insulin-like growth factor-1 (group 5), topical placebo (NaCl 9 mg/mL) and insulin (group 6), placebo (group 7), and a nondiabetic group receiving placebo (group 8). Seven to 14 animals were allocated to each group. Percentage wound closure 17 days after surgery in groups 1 and 2 were (mean +/- standard error of the mean) 25.5 +/- 5.3 and 32.2 +/- 6.3, respectively. Corresponding closure in groups 3, 4, and 5 was 55.7 +/- 5.0, 57.3 +/- 5.0, and 55.6 +/- 4.8, respectively (p < 0.05 vs. groups 1 and 2). Groups 6, 7, and 8 closed 32.0 +/- 4.5, 38.2 +/- 5.3, and 98.5 +/- 0.4%, respectively. Significant association between the number of AG-dosages and wound closure indicates dose-related effects in db/db mice. PMID- 22092797 TI - Evaluation of closed incision management with negative pressure wound therapy (CIM): hematoma/seroma and involvement of the lymphatic system. AB - The objective of this porcine study was to evaluate the effect of closed incision management with negative pressure wound therapy (CIM) on hematoma/seroma formation, fluid removal into the CIM canister, and involvement of the lymphatic system. In each swine (n = 8), two sets of ventral contralateral subcutaneous dead spaces with overlying sutured incisions were created. Stable isotope-labeled nanospheres were introduced into each subcutaneous dead space. Each contralateral incision was assigned to CIM (continuous -125 mmHg negative pressure) and control (semipermeable film dressing), respectively. Following 4 days of therapy, hematoma/seroma was weighed, total fluid volume in canisters was measured, five pre-identified lymph nodes were harvested, and five key organs were biopsied. There was 25 +/- 8 g (standard error [SE]) (63%) less hematoma/seroma in CIM sites compared to control sites (p = 0.002), without any fluid collection in the CIM canister. In lymph nodes, there were ~60 MUg (~50%) more 30- and 50-nm nanospheres from CIM sites than from control sites (p = 0.04 and 0.05, respectively). There was significantly greater nanosphere incidence from CIM sites than from control sites in lungs, liver, and spleen (p < 0.05); no nanospheres were detected in kidney biopsies. Thus, in this porcine model, application of CIM significantly decreased hematoma/seroma levels without fluid collection in the canister, which may be explained by increased lymph clearance. PMID- 22092798 TI - Selection of proangiogenic ascorbate derivatives and their exploitation in a novel drug-releasing system for wound healing. AB - The pathophysiology leading to delayed wound healing is complex and efficient therapeutic approaches for accelerated wound healing currently do not exist. We developed a novel drug-eluting platform for the potential use in wound dressings. Here, we report on the potential of eluting ascorbic acid-2-phosphate (ASC-2P), a highly stable variant of ascorbic acid, to induce angiogenesis and to promote collagen synthesis by fibroblasts. The drug-eluting platform device (DEPD) consists of biocompatible polymeric layers comprising polyethylene terephtalate, polyvinyl alcohol (PVA), and polyurethane with PVA as the solvent for ASC-2P. The angiogenic potential of ASC-2P was evaluated in the endothelial cell tube formation assay (TFA) and in the chorion allantoic membrane (CAM) model. Collagen synthesis by ASC-2P-stimulated fibroblasts was determined by Sirius Red staining. ASC-2P significantly induced angiogenesis in five independent TFA and CAM assays and induced collagen synthesis in two different fibroblast cell lines. The eluting kinetics of ASC-2P was determined by the ultraviolet NanoDrop method and the functional 2,2'-Azinobis-(3-ethylbenzthiazolin-6-sulfonic acid) method. Eluting profiles showed a continuous release in the range of biologically effective concentrations >10 days. This is the first report showing the proangiogenic- and collagen-promoting features of ASC-2P. DEPD loaded with ASC-2P ought to be further evaluated as wound dressings or as supplementary pads for topical treatment of delayed wound healing in preclinical studies. PMID- 22092799 TI - Wound healing in skin promoted by inoculation with Pseudomonas aeruginosa PAO1: The critical role of tumor necrosis factor-alpha secreted from infiltrating neutrophils. AB - Wound healing is promoted by the presence of replicating microorganisms adhering to the wounded tissue, but the precise mechanism is not fully understood. In the present study, using a rat model with full-thickness dermal wounds, we examined the effect of Pseudomonas aeruginosa inoculation on wound healing and the role of neutrophils infiltrating the wound site. Within 3 days, inoculation with this bacterium had accelerated re-epithelialization, epidermal cell proliferation, and neo-vascularization, as well as the local infiltration of neutrophils, which reached a peak at 24 hours. Tumor necrosis factor (TNF)-alpha was detected in the wound tissues on the mRNA and protein levels within 24 hours. Flow cytometry and immunohistochemical analyses detected higher levels of TNF-alpha in the infiltrating neutrophils in rats inoculated with P. aeruginosa than in uninoculated rats. Neutropenic rats treated with anti-neutrophil mAb or cyclophosphamide exhibited significant attenuation in re-epithelialization, epidermal cell proliferation, neo-vascularization, and TNF-alpha synthesis compared with control; administration of TNF-alpha reversed these attenuations. These wound-healing responses were decelerated in rats treated with anti-TNF alpha mAb, as was the infiltration of neutrophils. These results indicate that inoculation with P. aeruginosa promotes wound healing by inducing the infiltration of neutrophils, which play a critical role as a major source of TNF alpha. PMID- 22092800 TI - Spatiotemporal progression of cell death in the zone of ischemia surrounding burns. AB - Burns are dynamic injuries, characterized by progressive death of surrounding tissue over time. Although central to an understanding of burn injury progression, the spatiotemporal degrees and rates of cellular necrosis and apoptosis in the zone of ischemia surrounding burns are not well characterized. Using a validated porcine hot comb model, we probed periburn tissue at 1, 4, and 24 hours after injury for high-mobility group box 1 as a marker of necrosis and activated cleaved caspase-3 as a marker of apoptosis, followed by spatiotemporal morphometric analysis. We found that necrosis was the most prominent mechanism of cell death in burn injury progression, with significant progression between 1 and 4 hours postburn. Apoptosis appeared not to play a role in early burn injury progression but was observed in cells at the interface of necrotic and viable tissue at 24 hours postburn. Our findings imply that intervention within the first 4 hours following injury is likely necessary to limit burn injury progression. Additionally, based on high-mobility group box 1 staining patterns, we define distinct early, intermediate, and late pathological signs of cell necrosis that may facilitate delineation of causal mechanistic relationships of burn injury progression in vivo. PMID- 22092801 TI - Acceleration of diabetic-wound healing with PEGylated rhaFGF in healing-impaired streptozocin diabetic rats. AB - Molecular modification with polyethylene glycol (PEGylation) is an effective approach to improve protein biostability, in vivo lifetime and therapeutic potency. In the present study, the recombinant human acid fibroblast growth factor (rhaFGF) was site-selectively PEGylated with 20 kDa mPEG-butyraldehyde. Mono-PEGylated rhaFGF was purified to near homogeneity by Sephadex G 25-gel filtration followed by a Heparin Sepharose TM CL-6B affinity chromatography. PEGylated rhaFGF has less effect than the native rhaFGF on the stimulation of 3T3 cell proliferation in vitro; however, its relative thermal stability at normal physiological temperature and structural stability were significantly enhanced, and its half-life time in vivo was significantly extended. Then, the physiological function of PEGylated rhaFGF on diabetic-wound healing was evaluated in type 1 diabetic Sprague Dawley rats. The results showed that, compared with the group of animal treated with native rhaFGF, the group treated with PEGylated rhaFGF exhibited better therapeutic efficacy with shorter healing time, quicker tissue collagen generation, earlier and higher transforming growth factor (TGF)-beta expression, and dermal cell proliferation. In addition, in vivo analysis showed that both native and PEGylated rhaFGF were more effective in the wound healing in the diabetic group compared with the nondiabetic one. Taken together, these results suggest that PEGylation of rhaFGF could be a more effective approach to the pharmacological and therapeutic application of native rhaFGF. PMID- 22092802 TI - The electric field near human skin wounds declines with age and provides a noninvasive indicator of wound healing. AB - Due to the transepidermal potential of 15-50 mV, inside positive, an injury current is driven out of all human skin wounds. The flow of this current generates a lateral electric field within the epidermis that is more negative at the wound edge than at regions more lateral from the wound edge. Electric fields in this region could be as large as 40 mV/mm, and electric fields of this magnitude have been shown to stimulate human keratinocyte migration toward the wounded region. After flowing out of the wound, the current returns through the space between the epidermis and stratum corneum, generating a lateral field above the epidermis in the opposite direction. Here, we report the results from the first clinical trial designed to measure this lateral electric field adjacent to human skin wounds noninvasively. Using a new instrument, the Dermacorder(r), we found that the mean lateral electric field in the space between the epidermis and stratum corneum adjacent to a lancet wound in 18-25-year-olds is 107-148 mV/mm, 48% larger on average than that in 65-80-year-olds. We also conducted extensive measurements of the lateral electric field adjacent to mouse wounds as they healed and compared this field with histological sections through the wound to determine the correlation between the electric field and the rate of epithelial wound closure. Immediately after wounding, the average lateral electric field was 122 +/- 9 mV/mm. When the wound is filled in with a thick, disorganized epidermal layer, the mean field falls to 79 +/- 4 mV/mm. Once this epidermis forms a compact structure with only three cell layers, the mean field is 59 +/- 5 mV/mm. Thus, the peak-to-peak spatial variation in surface potential is largest in fresh wounds and slowly declines as the wound closes. The rate of wound healing is slightly greater when wounds are kept moist as expected, but we could find no correlation between the amplitude of the electric field and the rate of wound healing. PMID- 22092804 TI - Minimally invasive transcrestal sinus floor elevation with graft biomaterials. A randomized clinical trial. AB - OBJECTIVES: The present study was performed to comparatively evaluate the effectiveness and post-operative morbidity of transcrestal sinus floor elevation (tSFE) performed with a minimally invasive procedure (Smart Lift technique) combined with the additional use of two graft biomaterials. METHODS: Thirty sites in 30 patients were randomly assigned to tSFE in association with either deproteinized bovine bone mineral (DBBM) (n = 15) or synthetic hydroxyapatite in a collagen matrix (S-HA) (n = 15). In both groups, the extent of the sinus lift (SL) and the height of the graft apical to the implant apex (aGH) were assessed on periapical radiographs taken immediately after surgery and at 6 months following surgery. Surgical and post-surgical complications as well post-surgical pain and discomfort were also assessed. RESULTS: The results of the study indicated that (i) immediately post-surgery, both DBBM and S-HA resulted in substantial SL and aGH, which were maintained at 6 months, (ii) greater aGH and SL were observed in S-HA group compared with DBBM group at 6 months post-surgery and (iii) limited surgical complications and post-operative pain/discomfort were associated with the use of both graft biomaterials. CONCLUSIONS: The Smart Lift technique in conjunction with the additional use of either S-HA or DBBM may provide a predictable elevation of the maxillary sinus floor along with limited post-surgical complications and post-operative pain/discomfort. SL and aGH were significantly greater at 6 months for S-HA than DBBM. PMID- 22092805 TI - Pasteuria endospores from Heterodera cajani (Nematoda: Heteroderidae) exhibit inverted attachment and altered germination in cross-infection studies with Globodera pallida (Nematoda: Heteroderidae). AB - The Pasteuria group of Gram-positive, endospore-forming bacteria are parasites of invertebrates and exhibit differences in host specificity. We describe a cross infection study between an isolate of Pasteuria from pigeon pea cyst nematode, Heterodera cajani, which also infects the potato cyst nematode, Globodera pallida, from the United Kingdom. A proportion of the attached endospores, 13% on H. cajani and 22% on G. pallida adhere to the cuticle in an inverted orientation. Inverted and conventionally attached endospores germinated and produced bacillus like rods that completed their life cycle in < 15 weeks within females of G. pallida. This is the first example in which the life cycle of a Pasteuria population was systematically followed in two different nematode genera. A 1430 base pair fragment of the 16S rRNA gene sequence of the Pasteuria isolate from H. cajani revealed 98.6% similarity to the orthologous gene in Pasteuria nishizawae. Additionally, their respective endospore sizes were not significantly different, in contrast their host ranges are. Potential reasons for this remain unclear and are discussed. PMID- 22092806 TI - Titanium-zirconium alloy narrow-diameter implants (Straumann Roxolid((r))) for the rehabilitation of horizontally deficient edentulous ridges: prospective study on 18 consecutive patients. AB - AIM OF THE STUDY: (i) To evaluate the survival and success rates of the new Roxolid narrow diameter implant placed in horizontally deficient ridges; and (ii) to evaluate the incidence of prosthetic complications. MATERIALS AND METHODS: In a 24-month period (2009-2010) 18 partially or totally edentulous patients received 51 Straumann Roxolid (13 tissue level, 38 bone level) implants. Prosthetic loading of implants was either immediate (four implants; one patient) or delayed (2-12 months after placement; 47 implants; 17 patients). The patients were rehabilitated with either fixed (16 patients; 45 implants) or removable (two patients; six implants) prostheses. RESULTS: All implants successfully achieved osseointegration and all patients completed the planned prosthetic rehabilitation. Peri-implant bone resorption values ranged from 0 to 1 mm at the end of the observation period (range: 3-19 months). Implant survival and success rates were therefore 100%. No prosthetic complications occurred and all implants are still in function; therefore the prosthesis success rate was 100%. CONCLUSION: Narrow diameter implants fabricated with the new titanium-zirconium alloy were demonstrated to be reliable in supporting both fixed and removable prosthetic rehabilitations in horizontally deficient ridges. Implant survival, peri-implant bone resorption, and prosthetic complication rates were consistent with those reported in the literature for standard diameter implants placed in non-deficient edentulous ridges. PMID- 22092807 TI - The preliminary study of the relationship between facial movements and wrinkle formation. AB - BACKGROUND: As facial wrinkles develop particularly in areas of the skin that are subject to repeated facial movements, the degree of facial movements may be related to the degree of facial wrinkles, although no data have been reported. METHODS: Wrinkles were graded on the faces of Japanese female subjects when they made strong voluntary facial movements (eyes closed tightly, raised eyebrows, and frowns) and also when they were at rest using a set of photos (a photo scale) obtained from subjects with different degrees of wrinkles in the static and dynamic states. Scores obtained were compared between the dynamic and static states, and were analyzed in relation to age and to facial region. RESULTS: We found that the levels of wrinkles in both states showed a significant positive correlation with age. Further, the distribution of wrinkles in the dynamic state was found to be similar to those in the static states. Finally, the correlations between static and dynamic wrinkles in the same facial sites were higher than those in different facial sites. CONCLUSION: Facial movements cause wrinkling in both the dynamic and the static states and also that static wrinkles may work at the kinetic origins of dynamic wrinkles. PMID- 22092808 TI - Aspergillus biofilms: clinical and industrial significance. AB - The biofilm phenotype is an increasingly important concept in mycological research. Recently, there has been a developing interest in whether Aspergillus species are truly able to form biofilms or not. Industrial mycologists have long been aware of biofilms and their benefit in fermentation processes, whereas clinically their role is uncertain. This review provides an update on the impact that Aspergillus biofilms have medically and industrially, and will discuss biofilm development, and our current understanding of its molecular basis. The role of exopolymeric substance and how this substance relates to antimicrobial recalcitrance will also be discussed. PMID- 22092809 TI - The pro-region of Streptomyces hygroscopicus transglutaminase affects its secretion by Escherichia coli. AB - Streptomyces transglutaminase (TGase) is secreted as a zymogen (pro-TGase) in liquid cultures and is then processed by the removal of its N-terminal region, resulting in active TGase. To date, there is no report describing TGase (or pro TGase) secretion in Escherichia coli. In this study, the pro-TGase from Streptomyces hygroscopicus was efficiently secreted by E. coli BL21(DE3) using the TGase signal peptide or the pelB signal peptide. The secreted pro-TGase was efficiently transformed into active TGase by adding dispase to the culture supernatant of the recombinant strains. Mutational analysis showed that deletion of the first six amino acids of the N-terminal of the pro-region reduced the secretion of pro-TGase, and removal of the next 10 amino acids resulted in the formation of insoluble pro-TGase. These results suggest that the pro-region of TGase is essential for its efficient secretion and solubility in E. coli. PMID- 22092810 TI - Response to mercury (II) ions in Methylococcus capsulatus (Bath). AB - The mercury (II) ion is toxic and is usually detoxified in Bacteria by reduction to elemental mercury, which is less toxic. This is catalysed by an NAD(P)H dependent mercuric reductase (EC 1.16.1.1). Here, we present strong evidence that Methylococcus capsulatus (Bath) - a methanotrophic member of the Gammaproteobacteria - uses this enzyme to detoxify mercury. In radiorespirometry studies, it was found that cells exposed to mercury dissimilated 100% of [(14) C] methane provided to generate reducing equivalents to fuel mercury (II) reduction, rather than the mix of assimilation and dissimilation found in control incubations. The detoxification system is constitutively expressed with a specific activity of 352 (+/-18) nmol NADH oxidized min(-1) (mg protein)(-1) . Putative mercuric reductase genes were predicted in the M. capsulatus (Bath) genome and found in mRNA microarray studies. The MerA-derived polypeptide showed high identity (> 80%) with MerA sequences from the Betaproteobacteria. PMID- 22092811 TI - Plasmid-mediated transfer of the bla(NDM-1) gene in Gram-negative rods. AB - The latest threat of multidrug-resistant Gram-negative bacteria corresponds to the emergence of carbapenemase NDM-1 (New Delhi metallo-beta-lactamase) producers, mostly in Enterobacteriacae. Five bla(NDM) (-1) -positive plasmids of different incompatibility groups (IncL/M, FII, A/C and two untypeable plasmids) from clinical Enterobacteriaceae were evaluated for conjugation properties and host specificity. Successful conjugative transfers were obtained using all tested enterobacterial species as recipients (Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium and Proteus mirabilis) and all plasmid types. Conjugation frequencies varied from 1 * 10(-4) to 6 * 10(-8) transconjugants per donor. Higher conjugation rates were obtained for two plasmids at 30 degrees C compared with that observed at 25 and 37 degrees C. Carbapenems used as selector did not lead to higher conjugation frequencies. None of the five plasmids was transferable to Acinetobacter baumannii or Pseudomonas aeruginosa by conjugation. This work underlines how efficient the spread of the carbapenemase bla(NDM) (-1) gene could be among Enterobacteriaceae. PMID- 22092812 TI - Genetic analysis of the capsular polysaccharide synthesis locus in 15 Streptococcus suis serotypes. AB - The capsular polysaccharide (CPS) synthesis locus of 13 Streptococcus suis serotypes (serotype 1, 3, 4, 5, 7, 8, 9, 10, 14, 19, 23, 25 and 1/2) was sequenced and compared with that of serotype 2 and 16. The CPS synthesis locus of these 15 serotypes falls into two genetic groups. The locus is located on the chromosome between orfZ and aroA. All the translated proteins in the CPS synthesis locus were clustered into 127 homology groups using the tribemcl algorithm. The general organization of the locus suggested that the CPS of S. suis could be synthesized by the Wzy-dependent pathway. The capsule of serotypes 3, 4, 5, 7, 9, 10, 19 and 23 was predicted to be amino-polysaccharide. Sialic acid was predicted to be present in the capsule of serotypes 1, 2, 14, 16 and 1/2. The characteristics of the CPS synthesis locus suggest that some genes may have been imported into S. suis (or their ancestors) on multiple occasions from different and unknown sources. PMID- 22092813 TI - Multilocus sequence typing (MLST) for the infra-generic taxonomic classification of entomopathogenic Rickettsiella bacteria. AB - The genus Rickettsiella comprises intracellular bacterial pathogens of a wide range of arthropods that are currently classified in four recognized species and numerous further pathotypes. However, both the delineation of and the synonymization of pathotypes with species are highly problematic. In the sequel of a previous phylogenomic study at the supra-generic level, nine selected genes the 16S and 23S rRNA genes and the protein-encoding genes dnaG, ftsY, gidA, ksgA, rpoB, rpsA, and sucB - were evaluated for their potential as markers for the generic and infra-generic taxonomic classification of Rickettsiella-like bacteria. A methodological approach combining phylogenetic reconstruction with likelihood-based significance testing was employed on the basis of sequence data from the species Rickettsiella grylli and Rickettsiella popilliae, pathotypes 'Rickettsiella melolonthae' and 'Rickettsiella tipulae'. This study provides the first multilocus sequence typing (MLST) data for the genus Rickettsiella and identifies two new genetic markers, gidA and sucB, for the infra-generic classification within this taxon. In particular, aforesaid genes were found more reliable and informative markers than the corresponding 16S rRNA-encoding sequences that failed to produce strictly significant infra-generic taxonomic assignments. However, gidA- and sucB-based phylogenies were consistent with the currently accepted view of species delineation and species-pathotype synonymization within the genus Rickettsiella. PMID- 22092814 TI - Characterization of the Streptococcus suis XerS recombinase and its unconventional cleavage of the difSL site. AB - XerC and XerD are members of the tyrosine recombinase family and mediate site specific recombination that contributes to the stability of circular chromosomes in bacteria by resolving plasmid multimers and chromosome dimers to monomers prior to cell division. Homologues of xerC/xerD genes have been found in many bacteria, and in the lactococci and streptococci, a single recombinase called XerS can perform the functions of XerC and XerD. The xerS gene of Streptococcus suis was cloned, overexpressed and purified as a maltose-binding protein (MBP) fusion. The purified MBP-XerS fusion showed specific DNA-binding activity to both halves of the dif site of S. suis, and covalent protein-DNA complexes were also detected with dif site suicide substrates. These substrates were also cleaved in a specific fashion by MBP-XerS, generating cleavage products separated by an 11 bp spacer region, unlike the traditional 6-8-bp spacer observed in most tyrosine recombinases. Furthermore, xerS mutants of S. suis showed significant growth and morphological changes. PMID- 22092815 TI - SlyA regulator is involved in bile salts stress response of Enterococcus faecalis. AB - SlyA is a newly transcriptional regulator identified in Enterococcus faecalis that is involved in the virulence, persistence in mouse kidneys and liver, and survival inside peritoneal macrophages. In this study we searched for environmental conditions that affect expression of the corresponding gene. Of the several stress conditions tested, only bile salts (0.08%) significantly induced transcription of slyA. In addition, the growth of DeltaslyA mutant strain was significantly impaired in the presence of bile salts. To increase knowledge of SlyA regulon, real-time quantitative PCR was performed and revealed that expression of EF_3005, which encodes a choloylglycine hydrolase, is negatively regulated by SlyA. PMID- 22092816 TI - Isoalantolactone protects against Staphylococcus aureus pneumonia. AB - Staphylococcus aureus is a versatile pathogen that can cause life-threatening infections. The growing emergence of methicillin-resistant S. aureus strains and a decrease in the discovery of new antibiotics warrant the search for new therapeutic targets to combat infections. Staphylococcus aureus produces many extracellular virulence factors that contribute to its pathogenicity. Therefore, targeting bacterial virulence as an alternative strategy to the development of new antimicrobials has gained great interest. alpha-Toxin is a 33.2-kDa, water soluble, pore-forming toxin that is secreted by most S. aureus strains. alpha Toxin is essential for the pathogenesis of pneumonia, as strains lacking alpha toxin display a profound defect in virulence. In this report, we demonstrate that isoalantolactone (IAL), a naturally occurring compound found in Inula helenium (Compositae), has no anti-S. aureus activity as per MIC evaluation in vitro. However, IAL can markedly inhibit the expression of alpha-toxin in S. aureus at very low concentrations. Furthermore, the in vivo data indicate that treatment with IAL protects mice from S. aureus pneumonia. PMID- 22092817 TI - Identification of the Vibrio parahaemolyticus type III secretion system 2 associated chaperone VocC for the T3SS2-specific effector VopC. AB - The enteropathogen Vibrio parahaemolyticus possesses two sets of type III secretion systems, T3SS1 and T3SS2. Effector proteins secreted by these T3SSs are delivered into host cells, leading to cell death or diarrhea. However, it is not known how specific effectors are secreted through a specific T3SS when both T3SSs are expressed within bacteria. One molecule thought to determine secretion specificity is a T3SS-associated chaperone; however, no T3SS2-specific chaperone has been identified. Therefore, we screened T3SS2 chaperone candidates by a pull down assay using T3SS2 effectors fused with glutathione-S-transferase. A secretion assay revealed that the newly identified cognate chaperone VocC for the T3SS2-specific effector VopC was required for the efficient secretion of the substrate through T3SS2. Further experiments determined the chaperone-binding domain and the amino-terminal secretion signal of the cognate effector. These findings, in addition to the previously identified T3SS1-specific chaperone, VecA, provide a strategy to clarify the specificity of effector secretion through T3SSs of V. parahaemolyticus. PMID- 22092818 TI - Generating thermotolerant colonies by pairing Beauveria bassiana isolates. AB - Low thermotolerance in entomopathogenic fungi is the main impediment to their industrialization. This research, for the first time, describes the generation of a thermotolerant colony by pairing and subculturing (cycling) two Beauveria bassiana isolates without sexual reproduction. A mixture of B. bassiana ERL1578 and ERL1576 was inoculated on quarter-strength Sabouraud dextrose agar with yeast extract (1/4SDAY). The paired culture (ERL1578 + 1576) was cycled three times to increase the frequency of possible hyphal fusion at the first cycle (c. 5/5 * 10(5) conidia), followed by a heat treatment as a selection pressure. Two non paired isolates served as controls. Two morphologically different colonies (BbHet1 and BbHet2) were isolated from the pairing. BbHet1 colony had the highest conidial yield. BbHet2 had the most rapid mycelial growth and produced sponge like mycelial masses (the others were flat), and its conidia were darker than the non-paired colonies under a microscope (400*). BbHet2 conidia had 60.7% germination after exposure to 45 degrees C for 60 min (the others had < 15%) without significant loss of virulence against Western flower thrips, Frankliniella occidentalis; however, there was a slight decrease in conidial yield. The new phenotypes formed suggested that a genetic variation happened as a result of heterokaryosis and/or recombination, more than environmental adaptation, when mixing different conidia. This methodology seems to be very useful for enhancing thermotolerance in fungi. PMID- 22092819 TI - Mutation of pfm affects the adherence of Pseudomonas aeruginosa to host cells and the quorum sensing system. AB - The Pseudomonas aeruginosa quorum sensing (QS) system is controlled by the signal molecules acyl homoserine lactones (AHLs) that are synthesized from acyl enoyl acyl carrier proteins (acyl-ACPs) provided by the fatty acid biosynthesis cycle. Pfm (PA2950), an enoyl-CoA reductase, has previously been shown to affect swimming mobility and fatty acid biosynthesis. In this report, we further show that pfm influences bacterial adherence to human cells. Microarray assay results suggest that pfm affects bacterial adherence through its influence on the QS system. Further experiments confirmed that the pfm mutant strain produces significantly less QS signal molecules than the corresponding wild-type strain. Using strains Escherichia coli DH5alpha(pECP64, lasB'-lacZ) and E. coli DH5alpha(pECP61.5, rhlA'-lacZ), biosensors for N-(3-oxododecanoyl) homoserine lactone (3O-C(12) -HSL) and N-butyryl homoserine lactone (C(4) -HSL), respectively, we found that pfm mutant strain produces decreased amounts of both signal molecules. Elastase activity and pyocyanin measurements further confirmed the reduced levels of 3O-C(12) -HSL and C(4) -HSL in the pfm mutant. Finally, bacterial virulence, as assessed by the Caenorhabditis elegans worm killing assay, is decreased in the pfm mutant. Taken together, these data indicate that pfm can be an important target for the control of P. aeruginosa infectivity. PMID- 22092820 TI - Characterization of ISR region and development of a PCR assay for rapid detection of the fish pathogen Tenacibaculum soleae. AB - The aims of this work were to characterize the 16S-23S internal spacer region of the fish pathogen Tenacibaculum soleae and to develop a PCR assay for its identification and detection. All T. soleae strains tested displayed a single internal spacer region class, containing tRNA(I) (le) and tRNA(A) (la) genes; nevertheless, a considerable intraspecific heterogeneity was observed. However, this region proved to be useful for differentiation of T. soleae from related and non-related species. Species-specific primers were designed targeting the 16S rRNA gene and the internal spacer region region, yielding a 1555-bp fragment. Detection limit was of 1 pg DNA per reaction (< 30 bacterial cells) when using pure cultures. The detection level in the presence of DNA from fish or other bacteria was lower; however, 10 pg were detected at a target/background ratio of 1 : 10(5) . The PCR assay proved to be more sensitive than agar cultivation for the detection of T. soleae from naturally diseased fish, offering a useful tool for diagnosis and for understanding the epidemiology of this pathogen. PMID- 22092821 TI - Human cecum content modulates production of extracellular proteins by food and probiotic bacteria. AB - Lactic acid bacteria (LAB) are responsible for different types of food fermentations that provide humans with many different classes of fermented products. During the 20th century, some LAB strains as well as several members of the genus Bifidobacterium started to be extensively used in human nutrition as probiotics because of their health-promoting effects. Nowadays, the subset of extracellular proteins is being investigated as potential mediators of the process known as bacteria-host molecular crosstalk. Inclusion of human cecum extracts in laboratory culture medium modified the production of extracellular proteins by food and probiotic microorganisms. By proteomic and genetic means, the specific overproduction of two proteins was revealed to occur at transcriptional level. This work sheds light on the potential molecular effectors that food bacteria could use for interacting with the human gut and revealed that they may be produced under very specific environmental conditions. PMID- 22092822 TI - Periodontitis could be related factors on metabolic syndrome among Koreans: a case-control study. AB - AIM: Several studies have suggested that metabolic disorders are related to periodontitis. The objective of this study is to assess whether periodontitis is associated with the metabolic syndrome (MetS) among Koreans. MATERIAL AND METHODS: This case-control study was performed among 167 cases with MetS and 166 healthy controls from Shiwha-Banwol Environmental Health Cohort (N = 1853). The community periodontal index (CPI) was used to assess periodontitis (CPI 3-4). MetS was an outcome variable and periodontitis was a main explanatory variable. Age-gender-matched conditional logistic regression models were applied. Monthly household income, smoking, drinking, physical activity and diabetes mellitus were factored as confounders. We also performed stratified analyses according to confounders. RESULTS: Those with periodontitis are more likely to be patients with MetS than those without periodontitis. The adjusted odds ratio of periodontitis for MetS was 1.76. There was no significant dose-effect response on the relationship between the number of sextants with periodontitis and MetS. Links became higher in adults aged 45-60 years and adults without diabetes mellitus. CONCLUSIONS: These results suggest that periodontitis could be an independently related factor on MetS. Hence, dentists and physicians should be aware of the importance of periodontitis as a potential source of inflammatory burden. PMID- 22092824 TI - Gram-positive bacteria on grass pollen exhibit adjuvant activity inducing inflammatory T cell responses. AB - BACKGROUND: Recently, it has been established that pollen grains contain Th2 enhancing activities besides allergens. OBJECTIVE: The aim of this study was to analyse whether pollen carry additional adjuvant factors like microbes and what immunological effects they may exert. METHODS: Timothy pollen grains were collected and disseminated on agar plates, and the growing microorganisms were cultivated and defined. Furthermore, the immunologic effects of microbial products on DC and T cell responses were analysed. RESULTS: A complex mixture of bacteria and moulds was detected on grass pollen. Besides Gram-negative bacteria that are known to favour Th1-directed immune responses, moulds were identified as being sources of allergens themselves. Herein, we focused on Gram-positive bacteria that were found in high numbers, e.g. Bacillus cereus and Bacillus subtilis. Contact of immature dendritic cells (DC) from grass pollen allergic donors with supernatants of homogenized Gram-positive bacteria induced maturation of DC as measured by up-regulation of CD80, CD83 and CD86 and by enhanced production of IL-6, IL-12p40 and TNF-alpha, which was less pronounced compared with effects induced by lipopolysaccharide (LPS). Consequently, stimulation of autologous CD4(+) T cells with supernatants of homogenized Gram-positive bacteria plus grass pollen allergen-pulsed DC led to an enhanced proliferation and production of IL-4, IL-13, IL-10, IL-17, IL-22 and IFN-gamma production compared with T cells that were stimulated with allergen-pulsed immature DC alone, whereas production of the transcription factor for regulatory T cells FoxP3 was not significantly affected. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate that grass pollen is colonized by several microorganisms that influence the immune response differently. Similar to LPS, supernatants of homogenized Gram-positive bacteria may serve as adjuvants by augmenting DC maturation and inflammatory Th1, Th2 and Th17 responses helping to initiate allergic immune responses. PMID- 22092825 TI - A prospective study on implants installed with flapless-guided surgery using the all-on-four concept in the mandible. AB - AIM: Clinical data are scarce on flapless-guided surgery in the mandible using the all-on-four concept. In addition, limited documentation exists on the latter under immediate loading conditions with a pre-fabricated implant bridge. The aim was to provide detailed documentation focusing on clinical and radiographic outcome and complications. MATERIAL AND METHODS: Sixteen systemically healthy non smoking patients (10 women, 6 men, average age 59 years) with sufficient bone volume in the mandible were operated via flapless-guided surgery using the all-on four concept. Clinical and radiographic data and complications were registered at 3, 6 and 12 months. RESULTS: The overall implant survival rate was 90% with a trend for higher failure of short implants (P = 0.098). The mean bone level after 12 months of function was 0.83 mm with a maximum of 1.07 mm. Technical complications were common (15/16 patients). These mainly related to a misfit between the pre-fabricated prosthesis and abutment(s) (13/16 patients). CONCLUSION: If immediate loading of implants is pursued fabrication of the implant bridge should be based on actual impression of the implants at the time of surgery and not on their virtual position. PMID- 22092826 TI - Toivo Suutarinen--father of Finnish pediatric anesthesia. PMID- 22092827 TI - Methicillin-resistant Staphylococcus aureus from Northwest marine and freshwater recreational beaches. AB - The aim of the study was to determine the spatial distribution of methicillin resistant Staphylococcus aureus (MRSA) at two marine and one freshwater recreational beaches in the Seattle area. Fifty-six marine water, 144 freshwater, and 96 sand samples were collected from June through August 2010. Isolates were biochemically verified as MRSA. Staphylococcal cassette chromosome mec (SCCmec) typing, multilocus sequence typing (MLST), pulse field gel electrophoresis and the presence of other antibiotic resistance genes were determined. Twenty-two freshwater (15.3%; n = 144), one dry sand (1.9%; n = 53), six wet sand (14%; n = 43), and two marine water samples (3.6%; n = 56) were MRSA positive. Of the 27 freshwater stream sites sampled multiple times, 37% of the sites were positive for MRSA and/or S. aureus >= 2 times. Twenty-one (67.7%) of 31 MRSA were SCCmec type IV, 15 (48.4%) of the isolates had MLST types not previously associated with humans, and 29 (93.5%) of the isolates carried other antibiotic resistance genes. This study is the first to report and characterize repeated MRSA-positive samples from freshwater drainages and creeks surrounding popular recreational beaches. PMID- 22092828 TI - Patient satisfaction among Spanish-speaking patients in a public health setting. AB - Despite the growing literature on health care quality, few patient satisfaction studies have focused upon the public health setting; where many Hispanic patients receive care. The purpose of this study was to examine the differences in satisfaction between English and Spanish-speaking patients in a local health department clinical setting. We conducted a paper-based satisfaction survey of patients that visited any of the seven Jefferson County Department of Health primary care centers from March 19 to April 19, 2008. Using Chi-squared analyses we found 25% of the Spanish-speaking patients reported regularly having problems getting an appointment compared to 16.8% among English-speakers (p < .001). Results of logistic regression analyses indicated that, despite the availability of interpreters at all JCDH primary care centers, differences in satisfaction existed between Spanish and English speaking patients controlling for center location, purpose of visit, and time spent waiting. Specifically, Spanish speaking patients were more likely to report problems getting an appointment and less likely to report having their medical problems resolved when leaving their visit as compared to those who spoke English. Findings presented herein may provide insight regarding the quality of care received, specifically regarding patient satisfaction in the public health setting. PMID- 22092829 TI - In vivo investigations on the penetration of various oils and their influence on the skin barrier. AB - BACKGROUND: The skin represents a potent barrier to the environment, which can be enhanced by the topical application of skin care products, such as oil and oil based formulations by moisturizing the skin. METHODS: The aim of this study was the investigation of the penetration behaviour of four vegetable oils and of paraffin oil into the stratum corneum by laser scanning microscopy. In addition, the occlusion capacity of these substances was assessed by transepidermal water loss (TEWL) measurements. Petrolatum served as a positive control for skin occlusion. The study was conducted in vivo and included six healthy volunteers. RESULTS: Paraffin oil, as well as the vegetable oils, penetrated only into the first upper layers of the stratum corneum. TEWL measurements indicated that the application of the vegetable oils (except jojoba oil) as well as paraffin oil, led to a similar occlusion of the skin surface. The most effective occlusion was found for petrolatum. CONCLUSION: For the investigated oils, a deeper penetration than into the first upper layers of the stratum corneum could be excluded. The decreased TEWL values indicate that the application of the oils leads to a semi occlusion of the skin surface as it is intended by the use of oils to retain moisture in skin. PMID- 22092830 TI - Inferiorly based crescentic "sliding" cheek flaps for the reconstruction of paranasal surgical defects. PMID- 22092831 TI - Anti-infective surgical therapy of peri-implantitis. A 12-month prospective clinical study. AB - AIM: The aim of this prospective cohort study was to evaluate an anti-infective surgical protocol for the treatment of peri-implantitis. MATERIALS AND METHODS: Thirty-six implants in 24 partially dentate patients with moderate to advanced peri-implantitis were treated using an anti-infective surgical protocol incorporating open flap debridement and implant surface decontamination, with adjunctive systemic amoxicillin and metronidazole. Treatment outcomes were assessed at 3, 6 and 12 months. Patient-based statistical analyses using multiple regression analyses were performed. RESULTS: There was 100% survival of treated implants at 12 months. At 3 months, there were statistically significant (P < 0.01) reductions in mean probing depths (PD), Bleeding on Probing (BoP) and suppuration. The greater the mean PD at baseline, the greater the PD reduction at 3 months. At 3 months, there was also a significant mean facial mucosal recession of 1 mm (P < 0.001). All these changes were maintained at 6 and 12 months. At 12 months, all treated implants had a mean PD < 5 mm, while 47% of the implants had complete resolution of inflammation (BoP negative). At 12 months, 92% of implants had stable crestal bone levels or bone gain. There were no significant effects of smoking on any of the treatment outcomes. CONCLUSIONS: For the treatment of peri implantitis, an anti-infective protocol incorporating surgical access, implant surface decontamination and systemic antimicrobials followed by a strict postoperative protocol was effective at 3 months with the results maintained for up to 12 months after treatment. PMID- 22092832 TI - Do patients with chronic patellar tendinopathy have an altered somatosensory profile? A Quantitative Sensory Testing (QST) study. AB - The prevalence of tendinopathies in sports is high. The etiology and pain mechanisms of tendinopathies are not completely understood. Currently, little is known whether, or to which degree, somatosensory changes within the nervous system may contribute to the pain in tendinopathies. We conducted a patient controlled study in which we used the standardized QST protocol developed by the German Research Network on Neuropathic Pain. This protocol consists of seven different tests that measures 13 somatosensory parameters and can be seen as the gold standard to measure somatosensory function. Twelve athletes with clinically diagnosed chronic patellar tendinopathy (PT) mean duration 30 months (range 6 120) and 20 controls were included in the study. In two of the 13 QST parameters namely Mechanical Pain Threshold (P < 0.05) and Vibration Disappearance Threshold (P < 0.5) injured athletes were significantly more sensitive for the applied stimuli. None of the athletes had signs of Dynamic Mechanical Allodynia. Reduced mechanical pain thresholds or pinprick allodynia reflects the involvement of central sensitization upon the myelinated (Adelta-fibre) nociceptive input. From this explorative study, we conclude that sensitization may play a prominent role in the pain during and after sports activity in patella tendinopathy patients. PMID- 22092833 TI - Fatigue in female breast cancer patients: might its origins be more generic than we think? PMID- 22092834 TI - Interactions of bacteria with different mechanisms for chitin degradation result in the formation of a mixed-species biofilm. AB - In this study, interactions between bacteria possessing either released or cell associated enzymes for polymer degradation were investigated. For this, a co culture of Aeromonas hydrophila strain AH-1N as an enzyme-releasing bacterium and of Flavobacterium sp. strain 4D9 as a bacterium with cell-associated enzymes was set up with chitin embedded into agarose beads to account for natural conditions, under which polymers are usually embedded in organic aggregates. In single cultures, strain AH-1N grew with embedded chitin, while strain 4D9 did not. In co cultures, strain 4D9 grew and outcompeted strain AH-1N in the biofilm fraction. Experiments with cell-free culture supernatants containing the chitinolytic enzymes of strain AH-1N revealed that growth of strain 4D9 in the co-culture was based on intercepting N-acetylglucosamine from chitin degradation. For this, strain 4D9 had to actively integrate into the biofilm of strain AH-1N. This study shows that bacteria using different chitin degradation mechanisms can coexist by formation of a mixed-species biofilm. PMID- 22092835 TI - The use of transcutaneous oximetry to predict complications of chronic wound healing: a systematic review and meta-analysis. AB - Transcutaneous oximetry (P(tc) O(2) ) has been proposed as a method to predict nonhealing of chronic wounds and the occurrence of healing complications. However, the validity of this method as an independent predictor and an optimal threshold value for this tool are poorly defined. We undertook a systematic review and meta-analysis to address these questions, searching five major medical databases, relevant review articles, and reference lists. We included all studies that used multivariable analysis to evaluate P(tc) O(2) for its ability to predict chronic wound healing complications. Article selection and data abstraction were conducted independently and in duplicate. Four studies, enrolling 901 patients with 910 lower extremity chronic wounds, met our inclusion criteria. These studies showed that a peri-wound P(tc) O(2) level below a cutoff of 20 mmHg or 30 mmHg was an independent predictor of chronic wound healing complications (odds ratio 3.21, 95% confidence interval 1.07-9.69, I(2) = 77%). A threshold value of 20 mmHg was used most frequently in the included studies and showed the strongest association. This review was limited by the small number of studies, a possible reporting bias, and heterogeneity. These results suggest that P(tc) O(2) measurements have independent prognostic value in the assessment of chronic wounds, but further research is required to confirm these findings and define an optimal threshold value. PMID- 22092836 TI - The effect of honey-coated bandages compared with silver-coated bandages on treatment of malignant wounds-a randomized study. AB - Malignant wounds (MWs) occur in 5-10% of all cancer patients. Malodor and exudation are the most common side effects. The aim was to determine the influence of honey-coated compared with silver-coated bandages on treatment of MWs. Patients were randomly selected to enter either group A (honey-coated bandages) or group B (silver-coated bandages). Parameters were the following: wound size, cleanliness, malodor, exudation, and wound pain. Digital photographs, visual analog scales (VAS), and wound morphology registration were used for measurement at baseline and following the 4-week intervention. Sixty-nine patients with MWs and advanced cancer, aged 47-90 (median 65.6), were included. No statistically significant difference was noted between the groups with respect to wound size, degree of cleanliness, exudation, malodor, and wound pain. There was a median decrease in wound size of 15 cm2 and 8 cm2 in group A and B, respectively (p = 0.63). Based on post-intervention pooled data from the groups, improvement was seen in 62% of the participants with respect to wound size and in 58% (n = 69) with respect to cleanliness. The VAS score for malodor (p = 0.007) and exudation (p < 0.0001) improved significantly post-intervention. Patients with reduced wound size had a median survival time of 387 days compared with 134 days in patients with no wound reduction (p = 0.003). The use of honey-coated and silver-coated bandages improved the outcome of MWs. No differences were found between the two regimens. Both types of bandages are recommended for use by patients with MWs containing tumor debris and necrosis. PMID- 22092837 TI - Reflectance confocal microscopy for the evaluation of acute epidermal wound healing. AB - The dynamic process of wound healing is routinely evaluated by clinical or histological evaluation. Recently, a number of non-invasive imaging techniques have been evaluated for their clinical applicability in dermatology. Among them, reflectance confocal microscopy (RCM) represents a non-invasive imaging technique that allows the in vivo characterization of the skin at near-histological resolution. The aim of this study was to monitor epidermal wound repair using RCM in a model of tissue damage induced by cryosurgery. For this purpose, contact cryosurgery was performed at -32 degrees C for 10 seconds on the volar forearm of five healthy volunteers. Clinical and RCM evaluations were performed at nine consecutive time points. RCM allowed the visualization of edema formation and blood vessel dilatation immediately after cryosurgery, as well as morphologic features of wound repair, including the formation of finger-like protusions of keratinocytes into the wound bed, the appearance of hairpin-like vessels, and inflammatory cells. This pilot study illustrates that RCM represents a promising technique for quasi-real-time monitoring the kinetics of wound repair non invasively and over time, thus offering new insights into in vivo processes of cutaneous wound repair and angiogenesis, as well as potential effects of topically applied drugs on the process of tissue repair. PMID- 22092838 TI - Everolimus-induced loss of wound strength can be prevented by a short postoperative delay in its administration. AB - The use of mammalian target of rapamycin inhibitors coincides with an increased incidence of surgical complications. In previous experiments, serious negative effects of postoperative everolimus on anastomotic strength were found. This study aims to investigate if delayed drug administration can prevent loss of wound strength. Ten groups of Wistar rats each received daily oral doses of 1.0 or 2.0 mg/kg everolimus, starting the day of anastomotic construction in both ileum and colon, or 1, 2, 3, or 4 days later. The 11th group received saline. Seven days later, wound strength in anastomoses and in the abdominal wall and wound hydroxyproline levels were measured. Mean wound strength was significantly and dose-dependently reduced if everolimus was started on the day of operation. In ileum and colon, strength was not affected if drug administration was delayed until the third or second day, respectively. In abdominal fascia, this was the case only if everolimus was withheld until day 4. In general, changes in wound hydroxyproline content showed similarities to changes in wound strength. Thus, delaying administration of everolimus for 2-4 days after operation can prevent a serious loss of wound strength, both in the intestine and in the abdominal fascia. PMID- 22092839 TI - Collagen matrix-bound clotting factors (CMBCF) promote healing-associated events independent of factor XIII in an in vitro model. AB - We have previously explored in vitro as well as in vivo models of the biological effects of liquid fibrin glue (FG) containing factor XIII. The fixed combination of a collagen matrix and coagulation factors I and IIa (TachoSil((r)) , Nycomed, Linz, Austria) is void of factor XIII. We aimed to determine whether (1) this preparation exerts similar effects to liquid FG on cells in an in vitro system, or (2) this effect is modulated by factor XIII. In an in vitro model, the effect of the fixed combination of collagen matrix and coagulation factors I and IIa (collagen matrix-bound clotting factor [CMBCF]) on the expression and secretion of growth factors (vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor-2) by gastric epithelial (AGS) and mesenchymal cells (fibroblasts), as well as their proliferative response (WST-test), was compared in the presence and absence of factor XIII. The use of CMBCF compared with collagen type I matrix resulted in an increased proliferation rate of fibroblasts; there was an increased secretion of fibroblast growth factor-2. Gastric epithelial cells secreted more vascular endothelial growth factor and platelet-derived growth factor into the culture supernatant in the presence of CMBCF. All responses remained unaltered by the addition of factor XIII in different concentrations. In conclusion, CMBCF exerted effects similar to liquid FG in an in vitro model of healing. The addition of factor XIII did not alter the response of mesenchymal or epithelial cells, with respect to proliferation and growth factor secretion. PMID- 22092840 TI - Acceleration of cutaneous healing by electrical stimulation: degenerate electrical waveform down-regulates inflammation, up-regulates angiogenesis and advances remodeling in temporal punch biopsies in a human volunteer study. AB - We previously demonstrated the beneficial effect of a novel electrical stimulation (ES) waveform, degenerate wave (DW) on skin fibroblasts, and now hypothesize that DW can enhance cutaneous wound healing in vivo. Therefore, a punch biopsy was taken from the upper arm of 20 volunteers on day 0 and repeated on day 14 (NSD14). A contralateral upper arm biopsy was taken on day 0 and treated with DW for 14 days prior to a repeat biopsy on day 14 (ESD14). A near completed inflammatory stage of wound healing in ESD14, compared to NSD14 was demonstrated by up-regulation of interleukin-10 and vasoactive intestinal peptide using quantitative real time polymerase chain reaction and down-regulation of CD3 by immunohistochemistry (IHC) (p < 0.05). In addition to up-regulation (p < 0.05) of mRNA transcripts for re-epithelialization and angiogenesis, IHC showed significant overexpression (p < 0.05) of CD31 (15.5%), vascular endothelial growth factor (66%), and Melan A (8.6 cells/0.95 mm2) in ESD14 compared to NSD14 (9.5%, 38% and 4.3 cells/0.95 mm2, respectively). Furthermore, granulation tissue formation (by hematoxylin and eosin staining), and myofibroblastic proliferation demonstrated by alpha-smooth muscle actin (62.7%) plus CD3+ T lymphocytes (8.1%) showed significant up-regulation (p < 0.05) in NSD14. In the remodeling stage, mRNA transcripts for fibronectin, collagen IV (by IHC, 14.1%) and mature collagen synthesis (by Herovici staining, 71.44%) were significantly up-regulated (p < 0.05) in ESD14. Apoptotic (TUNEL assay) and proliferative cells (Ki67) were significantly up-regulated (p < 0.05) in NSD14 (5.34 and 11.9 cells/0.95 mm2) while the proliferation index of ESD14 was similar to normal skin. In summary, cutaneous wounds receiving DW electrical stimulation display accelerated healing seen by reduced inflammation, enhanced angiogenesis and advanced remodeling phase. PMID- 22092841 TI - Augmentation of rat skin flap viability by relaxin-expressing adenovirus. AB - Relaxin (RLX) has multiple vascular actions, including vasodilation and angiogenesis, which occur via induction of vascular endothelial growth factor (VEGF) expression. We generated a RLX-expressing (dE1-RGD/lacZ/RLX) adenovirus and investigated whether it enhances skin flap survival. Thirty Sprague-Dawley rats were divided into three groups: RLX-expressing adenovirus group, control virus group, and phosphate-buffered saline (PBS) group. Two days before surgery and immediately after flap elevation, the caudally based flap that was 3 * 9 cm in size was subdermally injected with the dE1-RGD/lacZ/RLX virus (107 PFU), dE1 RGD/lacZ virus (107 PFU), or PBS. The surviving area of the flap and the amount of blood flow were measured. On postoperative day 10, CD31-positive vessels and VEGF protein expression were examined. We observed a significant increase in the survival area of the flap in the RLX group. Doppler measurement also showed significantly increased blood flow immediately after the operation and on postoperative days 7 and 10. CD31-positive vessels and VEGF protein expression were significantly greater in the RLX group. Thus, administration of RLX expressing adenovirus into elevated skin flaps increased VEGF expression, the number of capillaries, and blood flow to the flap, thereby improving skin flap survival. PMID- 22092842 TI - Extracellular matrix-derived tripeptide proline-glycine-proline inhibits keratinocyte proliferation and migration. AB - Keratinocytes are the predominant cell type in epidermis, and are primarily responsible for the epithelialization phase of wound healing. Previous studies by our group showed a positive correlation between IL-8 concentration and delayed healing of porcine cutaneous partial-thickness wounds. Interleukin-8 and collagen breakdown product N-acetyl-Pro-Gly-Pro (PGP) are known as chemoattractant molecules for neutrophils during inflammation. The activity of both molecules is dependent on chemokine receptors CXCR1 and CXCR2. In addition to neutrophils, keratinocytes also express CXCR1 and CXCR2. Here we investigated the effects of IL-8 and PGP on keratinocyte proliferation and migration. Our results showed that IL-8 up to 100 ng/mL does not have any significant impact on keratinocyte proliferation or migration. ECM-derived tripeptide PGP chemotactically attracts neutrophils but not keratinocytes. PGP strongly inhibits keratinocyte proliferation and migration in a cell-type specific manner. Thus, collagen breakdown product PGP plays a key role in modulating both the inflammatory and epithelialization phases of wound healing. PMID- 22092843 TI - Measurements of wound edge microvascular blood flow during negative pressure wound therapy using thermodiffusion and transcutaneous and invasive laser Doppler velocimetry. AB - The effects of negative pressure wound therapy (NPWT) on wound edge microvascular blood flow are not clear. The aim of the present study was therefore to further elucidate the effects of NPWT on periwound blood flow in a porcine peripheral wound model using different blood flow measurement techniques. NPWT at -20, -40, 80, and -125 mmHg was applied to a peripheral porcine wound (n = 8). Thermodiffusion, transcutaneous, and invasive laser Doppler velocimetry were used to measure the blood perfusion 0.5, 1.0, and 2.5 cm from the wound edge. Thermodiffusion (an invasive measurement technique) generally showed a decrease in perfusion close to the wound edge (0.5 cm), and an increase further from the edge (2.5 cm). Invasive laser Doppler velocimetry showed a similar response pattern, with a decrease in blood flow 0.5 cm from the wound edge and an increase further away. However, 1.0 cm from the wound edge blood flow decreased with high pressure levels and increased with low pressure levels. A different response pattern was seen with transcutaneous laser Doppler velocimetry, showing an increase in blood flow regardless of the distance from the wound edge (0.5, 1.0, and 2.5 cm). During NPWT, both increases and decreases in blood flow can be seen in the periwound tissue depending on the distance from the wound edge and the pressure level. The pattern of response depends partly on the measurement technique used. The combination of hypoperfusion and hyperperfusion caused by NPWT may accelerate wound healing. PMID- 22092844 TI - Multiplexed molecular descriptors of pressure ulcers defined by imaging mass spectrometry. AB - The pathogenesis of impaired healing within pressure ulcers remains poorly characterized and rarely examined. We describe the results of a pilot study that applies matrix-assisted laser desorption/ionization imaging mass spectrometry technology for direct tissue analysis to evaluate proteomic signatures ranging from 2 to 20 kDa and phospholipids from 300-1,200 Da in focal regions within the wound microenvironment. Distinguishing molecular differences were apparent between upper vs. lower regions of ulcers and further contrasted against adjacent dermis and epidermal margins using protein profiles, ion density maps, principal component analysis and significant analysis of microarrays. Several proteins previously uncharacterized in pressure ulcers, the alpha-defensins (human neutrophil peptide [HNP]-1, -2, -3), are potential markers indicating whether the wound status is improving or being prolonged in a deleterious, chronic state. Thymosin beta4 appears to be a favorable protein marker showing higher relative levels in adjacent dermis and maturing areas of the wound bed. Lipidomic examination revealed the presence of major lipid classes: glycerophosphocholines, glycerophosphoglycerols, glycerophosphoinositols, and triacylglycerols. Our pilot data examined from either a global perspective using proteomic or lipidomic signatures or as individual distributions reveal that imaging mass spectrometry technology can be effectively used for discovery and spatial mapping of molecular disturbances within the microenvironment of chronic wounds. PMID- 22092845 TI - CEACAM1 deficiency delays important wound healing processes. AB - Cutaneous wound healing is a complex process that requires the coordination of many cell types to achieve proper tissue repair. Four major overlapping processes have been identified in wound healing: hemostasis, inflammation, reepithelialization and granulation tissue formation, and tissue remodeling. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a glycoprotein expressed in epithelial, endothelial, lymphoid, and myeloid cells. Given its known roles in angiogenesis, cell migration, and immune functions, we hypothesized that CEACAM1 might also be involved in cutaneous wound healing and that a number of relevant CEACAM1-positive cell types might contribute to wound healing. To evaluate the role of CEACAM1 in these processes, 6-mm-diameter skin wounds were inflicted on Ceacam1(-/-) and wild-type mice. Herein, we demonstrate that CEACAM1 deletion indeed affects wound healing in three key ways. Infiltration of F4/80(+) macrophages was decreased in Ceacam1(-/-) wounds, altering inflammatory processes. Reepithelialization in Ceacam1(-/-) wounds was delayed. Furthermore, the vascular density of the granulation tissue in Ceacam1( /-) wounds was significantly diminished. These results confirm CEACAM1's role as an important regulator of key processes in cutaneous wound healing, although whether this works via a specific cell type or alterations in the functioning of multiple processes remains to be determined. PMID- 22092846 TI - Platelet-rich fibrin matrix improves wound angiogenesis via inducing endothelial cell proliferation. AB - The economic, social, and public health burden of chronic ulcers and other compromised wounds is enormous and rapidly increasing with the aging population. The growth factors derived from platelets play an important role in tissue remodeling including neovascularization. Platelet-rich plasma (PRP) has been utilized and studied for the last four decades. Platelet gel and fibrin sealant, derived from PRP mixed with thrombin and calcium chloride, have been exogenously applied to tissues to promote wound healing, bone growth, hemostasis, and tissue sealing. In this study, we first characterized recovery and viability of as well as growth factor release from platelets in a novel preparation of platelet gel and fibrin matrix, namely platelet-rich fibrin matrix (PRFM). Next, the effect of PRFM application in a delayed model of ischemic wound angiogenesis was investigated. The study, for the first time, shows the kinetics of the viability of platelet-embedded fibrin matrix. A slow and steady release of growth factors from PRFM was observed. The vascular endothelial growth factor released from PRFM was primarily responsible for endothelial mitogenic response via extracellular signal-regulated protein kinase activation pathway. Finally, this preparation of PRFM effectively induced endothelial cell proliferation and improved wound angiogenesis in chronic wounds, providing evidence of probable mechanisms of action of PRFM in healing of chronic ulcers. PMID- 22092847 TI - The efficacy of silver dressings and antibiotics on MRSA and MSSA isolated from burn patients. AB - In this study our objectives were (1) to investigate whether meticillin-resistant Staphylococcus aureus (MRSA) showed an increased tolerance to silver wound dressings compared with meticillin-sensitive S. aureus (MSSA); and (2) to evaluate the effects of bacterial phenotypic states of MRSA and MSSA, and pH, on the activity of silver wound dressings and two antibiotics, ampicillin and clindamycin. Twenty MRSA strains and 10 MSSA strains isolated from burns patients in South Africa were evaluated for their susceptibility to a silver alginate and a silver carboxymethyl cellulose wound dressing, employing a corrected zone of inhibition assay, conducted on Mueller Hinton agar and a poloxamer-based biofilm model. When exposed to the two silver dressings, all 30 S. aureus strains showed susceptibility. Possible enhanced antimicrobial efficacy of the silver dressings occurred when pH was lowered to 5.5, compared with a pH of 7.0. When all S. aureus were grown in the biofilm phenotypic state and exposed to both silver dressings and antibiotics, enhanced tolerance was noted. Susceptibility to silver was overall higher for MRSA when compared with MSSA. This study showed that the effect of pH and bacterial phenotypic state must be considered when the antimicrobial activity of silver wound dressings is being investigated. It is evident from the data generated that both pH and the bacterial phenotypic state are factors that induce changes that affect both antimicrobial performance and bacterial susceptibility. PMID- 22092848 TI - Multiple pass ultrasound tightening of skin laxity of the lower face and neck. AB - BACKGROUND: Skin laxity is a common complaint of patients who request skin rejuvenation. Radiofrequency and infrared light are widely used for nonablative treatment of skin laxity. Intense focused ultrasound (IFUS) has been investigated as a tool for the treatment of solid benign and malignant tumors for many decades but is only now beginning to emerge as a potential noninvasive alternative to conventional nonablative therapy. OBJECTIVES: To evaluate the efficacy of IFUS for the treatment of face and neck laxity. METHODS: Twelve female volunteers were enrolled in the study, and 10 were ultimately evaluated. The device under investigation was an IFUS. Areas treated included the face and neck. For treatment, the 4-MHz, 4.5-mm probe was used first, followed by the 7-MHz, 3.0-mm probe. Two blinded, experienced clinicians evaluated paired pretreatment and post treatment (day 90) photographs. Patient self-assessments were also obtained. RESULTS: On the first primary outcome measure, two blinded clinicians felt that 8 of 10 subjects (80%) showed clinical improvement 90 days after treatment. Nine of 10 subjects (90%) reported subjective improvement. CONCLUSIONS: IFUS has many advantages for skin tightening. PMID- 22092849 TI - Knee injuries related to sports in young adult males during military service - incidence and risk factors. AB - The population-based incidence and risk factors for knee injuries in young adults were assessed in Finnish male conscripts performing their compulsory military service (n = 128,584). The main outcome variables were (1) hospitalization due to knee injuries overall and (2) hospitalization due to knee disorders as categorized into specific International Classification of Diseases, tenth revision diagnoses (cruciate and collateral ligament tears, meniscal tears, traumatic chondral lesions, and patellar dislocations). Person-time injury incidence rates were calculated by dividing the number of persons with a diagnosed knee injury by the total exposure time of 97,503 person-years. The number of subjects with surgical operations and military service class changes indicative of longer term notable disability are also reported. Risk factor analyses were performed by logistic regression. The person-based incidence of hospitalizations for knee injury was 11 cases per 1000 person-years [95% confidence interval (CI): 10.4-11.7]. The most important risk factors were higher age (odds ratio 1.7; 95% CI: 1.3-2.2) and obesity (odds ratio 1.6; 95% CI: 1.03 2.5). Two thirds of all subjects hospitalized for knee injuries had surgery, and one third had longer term notable disability. These findings indicate that knee injuries cause a significant burden of hospitalizations, often leading to surgery and longer term disability. PMID- 22092850 TI - Patch testing: what allergists should know. AB - Patch testing is a standardized, in vivo diagnostic test for type IV hypersensitivity reactions, resulting in allergic contact dermatitis, which clinically resembles eczema. Common allergens include fragrance chemicals, hair dyes, metals, rubber accelerators and preservatives. Known allergens at particular concentrations in optimal vehicles are tested on the upper back under occlusion for 2 days. Readings according to international criteria are usually performed on days 2 and 4. Irritant reactions can closely resemble allergic ones, and further tests may be necessary to discriminate. Interpretation of the relevance of the reactions can also be difficult, perhaps requiring repeated open application testing, work-site visits etc. Monitoring of trends in patch test positivity can be effective in primary prevention of type IV allergy. PMID- 22092851 TI - Effect of mismatching abutments on implants with wider platforms--an experimental study in dogs. AB - AIM: To evaluate the effect of mismatching abutments on implants with a wider platform on the peri-implant hard tissue remodeling and the soft tissue dimensions. MATERIAL AND METHODS: Mandibular premolars and first molars of six Labrador dogs were extracted bilaterally. After 3 months of healing, one tapered implant was installed on each side of the mandibular molar region with the implant shoulder placed at the level of the buccal alveolar bony crest. On the right side of the mandible, an abutment of reduced diameter in relation to the platform of the implant was used, creating a mismatch of 0.85 mm (test), whereas an abutment of the same diameter of the implant platform was affixed in the left side of the mandible (control). The flaps were sutured to allow a non-submerged healing. After 4 months, the animals were sacrificed and ground sections were obtained for histometric assessment. RESULTS: All implants were completely osseo integrated. Bone levels were superior at the test than at the control sites. However, statistically significant differences were found only at the buccal and proximal aspects. The soft tissue vertical dimension was higher at the control compared with the test sites. However, statistically significant differences were demonstrated only at the buccal aspects. CONCLUSIONS: A mismatch of 0.85 mm between the implant and the abutment yielded more coronal levels of bone-to implant contact and a reduced height of the peri-implant soft tissue (biologic width), especially at the buccal aspect, if the implant shoulder was placed flush with the level of the buccal alveolar bony crest. PMID- 22092852 TI - Sublethal ciprofloxacin treatment leads to resistance via antioxidant systems in Proteus mirabilis. AB - This study investigates new aspects of the possible role of antioxidant defenses in the mechanisms of resistance to ciprofloxacin in Proteus mirabilis. Four ciprofloxacin-resistant variants (CRVs), selected in vitro by repeated cultures in a sub-minimum inhibitory concentration (MIC) concentration of ciprofloxacin, attained different levels of antibiotic resistance and high Ferric reducing antioxidant power, with 10(-6) frequencies. However, no mutations occurred in positions 83 or 87 of gyrA, 464 or 466 of gyrB, or 78, 80 or 84 of parC, suggesting that resistance took place without these typical mutations in DNA gyrase or topoisomerase IV. Assays with ciprofloxacin and the pump inhibitor carbonyl cyanide m-chlorophenylhydrazone showed that in addition to the antioxidant mechanisms, the influx/efflux mechanism also contributed to the increase in the resistance to ciprofloxacin in one CRV. Moreover, lipid oxidation to malondialdehyde and protein oxidation to carbonyls and advanced oxidation protein products were higher in sensitive than in the resistant strains, as a new factor involved in the mechanisms of resistance in P. mirabilis. The oxidative stress cross-resistance to telluride in CRVs enhanced the role of the antioxidants in the ciprofloxacin resistance of P. mirabilis, which was reinforced during the assays of reduction of susceptibility to ciprofloxacin by glutathione and ascorbic acid. PMID- 22092853 TI - ICD arrhythmia detection and discrimination algorithms: whose is best? PMID- 22092854 TI - Using optical coherence tomography for the longitudinal non-invasive evaluation of epidermal thickness in a murine model of chronic skin inflammation. AB - BACKGROUND: Non-invasive methods are desirable for longitudinal studies examining drug efficacy and disease resolution defined as decreases in epidermal thickness in mouse models of psoriasiform skin disease. This would eliminate the need for either sacrificing animals or collecting serial skin biopsies to evaluate changes in disease progression during an individual study. The quantitation of epidermal thickness using optical coherence tomography (OCT) provides an alternative to traditional histology techniques. METHODS: Using the KC-Tie2 doxycycline repressible psoriasiform skin disease mouse model, OCT imaging was completed on diseased back skin of adult KC-Tie2 (n = 3-4) and control (n = 3-4) mice, followed immediately by the surgical excision of the same region for histologic analyses. Animals were then treated with doxycycline to suppress transgene expression and to reverse the skin disease and additional OCT images and tissues were collected 2 and 4 weeks following. Epidermal thickness was measured using OCT and histology. RESULTS: Optical coherence tomography and histology both demonstrated that KC-Tie2 mice had significantly thicker epidermis (~4-fold; P < 0.0001) than control animals. By 2 weeks following gene repression, decreases in epidermal thickness were observed using both OCT and histology, and were sustained through 4 weeks. Correlation analyses between histology and OCT values at all time points and in all animals revealed high significance (R(2) = 0.78); with correlation being highest in KC-Tie2 mice (R(2) = 0.92) compared to control animals (R(2) = 0.16). CONCLUSION: Non-invasive OCT imaging provided similar values as those collected using standard histologic measures in thick skin of KC Tie2 mice but became less reliable in thinner control mouse skin, possibly reflecting limitations in resolution of OCT. Future advances in resolution of OCT may improve and allow greater accuracy of epidermal thickness measurements. PMID- 22092855 TI - The Tat protein export pathway and its role in cyanobacterial metalloprotein biosynthesis. AB - The Tat pathway is a common protein translocation system that is found in the bacterial cytoplasmic membrane, as well as in the cyanobacterial and plant thylakoid membranes. It is unusual in that the Tat pathway transports fully folded, often metal cofactor-containing proteins across these membranes. In bacteria, the Tat pathway plays an important role in the biosynthesis of noncytoplasmic metalloproteins. By compartmentalizing protein folding to the cytoplasm, the potentially aberrant binding of non-native metal ions to periplasmic proteins is avoided. To date, most of our understanding of Tat function has been obtained from studies using Escherichia coli as a model organism but cyanobacteria have an extra layer of complexity with proteins targeted to both the cytoplasmic and thylakoid membranes. We examine our current understanding of the Tat pathway in cyanobacteria and its role in metalloprotein biosynthesis. PMID- 22092856 TI - Passage through Tetrahymena tropicalis enhances the resistance to stress and the infectivity of Legionella pneumophila. AB - Legionella pneumophila is a gram-negative bacterium prevalent in fresh water which accidentally infects humans and is responsible for the disease called legionellosis. Intracellular growth of L. pneumophila in Tetrahymena is inconsistent; in the species Tetrahymena tropicalis stationary-phase forms (SPFs) of L. pneumophila differentiate into mature intracellular forms (MIFs) without apparent bacterial replication and are expelled from the ciliate as pellets containing numerous MIFS. In the present work, we tested the impact of L. pneumophila passage through T. tropicalis. We observed that MIFs released from T. tropicalis are more resistant to various stresses than SPFs. Under our conditions, MIFs harboured a higher gentamicin resistance, maintained even after 3 months as pellets. Long-term survival essays revealed that MIFs survived better in a nutrient-poor environment than SFPs, as a reduction of only about 3 logs was observed after 4 months in the MIF population, whereas no cultivable SPFs were detected after 3 months in the same medium, corresponding to a loss of about 7 logs. We have also observed that MIFs are significantly more infectious in human pneumocyte cells compared with SPFs. These results strongly suggest a potential role of ciliates in increasing the risk of legionellosis. PMID- 22092857 TI - Bacillus thuringiensis Cry2Ab is active on Anopheles mosquitoes: single D block exchanges reveal critical residues involved in activity. AB - Cry2Aa exhibits dual activity to Lepidoptera and Diptera. Cry2Ab differs in amino acid sequence from Cry2Aa by 13% and has shown significant lepidopteran activity, but no mosquitocidal activity. Previous studies implicate 23 Cry2Aa specificity conferring residues of domain II, which differ in Cry2Ab. Nine residues are putatively involved in conferring Cry2Aa dipteran specificity. To explore Cry2Ab dipteran toxicity, site-directed mutagenesis was employed to exchange Cry2Ab residues with Cry2Aa D (dipteran) block residues. Cry2Ab wild type demonstrated high toxicity (LC(50) of 540 ng mL(-1)) to Anopheles gambiae, but not to Aedes or Culex, within a 24-h time period. Cry2Ab should be reclassified as a dual active Cry toxin. Cry2Ab mutagenesis revealed critical residues for Cry2Ab protein function, as well as enhanced activity against the malarial mosquito, An. gambiae. PMID- 22092858 TI - Duplication of partial spinosyn biosynthetic gene cluster in Saccharopolyspora spinosa enhances spinosyn production. AB - Spinosyns, the secondary metabolites produced by Saccharopolyspora spinosa, are the active ingredients in a family of insect control agents. Most of the S. spinosa genes involved in spinosyn biosynthesis are found in a contiguous c. 74 kb cluster. To increase the spinosyn production through overexpression of their biosynthetic genes, part of its gene cluster (c. 18 kb) participating in the conversion of the cyclized polyketide to spinosyn was obtained by direct cloning via Red/ET recombination rather than by constructing and screening the genomic library. The resultant plasmid pUCAmT-spn was introduced into S. spinosa CCTCC M206084 from Escherichia coli S17-1 by conjugal transfer. The subsequent single crossover homologous recombination caused a duplication of the partial gene cluster. Integration of this plasmid enhanced production of spinosyns with a total of 388 (+/- 25.0) mg L(-1) for spinosyns A and D in the exconjugant S. spinosa trans1 compared with 100 (+/- 7.7) mg L(-1) in the parental strain. Quantitative real time polymerase chain reaction analysis of three selected genes (spnH, spnI, and spnK) confirmed the positive effect of the overexpression of these genes on the spinosyn production. This study provides a simple avenue for enhancing spinosyn production. The strategies could also be used to improve the yield of other secondary metabolites. PMID- 22092859 TI - Rapid detection of vip1-type genes from Bacillus cereus and characterization of a novel vip binary toxin gene. AB - A PCR-restriction fragment length polymorphism (PCR-RFLP) method for identifying vegetative insecticidal protein (vip) 1-type genes from Bacillus cereus was developed by designing specific primers based on the conserved regions of the genes to amplify vip1-type gene fragments. PCR products were digested with endonuclease AciI, and four known vip1-type genes were identified. Vip1Ac and vip1Aa-type genes appeared in 17 of 26 B. cereus strains. A novel vip1-type gene, vip1Ac1, was identified from B. cereus strain HL12. The vip1Ac1 and vip2Ae3 genes were co-expressed in Escherichia coli strain BL21 by vector pCOLADuet-1. The binary toxin showed activity only against Aphis gossypii (Homoptera), but not for Coleptera (Tenebrio molitor, Holotrichia oblita), Lepidoptera (Spodoptera exigua, Helicoverpa armigera, and Chilo suppressalis), Diptera (Culex quinquefasciatus). The LC(50) of this binary toxin for A. gossypii is 87.5 (34.2-145.3) ng mL(-1) . This is probably only the second report that Vip1 and Vip2 binary toxin shows toxicity against homopteran pests. The PCR-RFLP method developed could be very useful for identifying novel Vip1-Vip2-type binary toxins, and the novel binary toxins, Vip1Ac1 and Vip2Ae3, identified in this study may have applications in biological control of insects, thus avoiding potential problems of resistance. PMID- 22092860 TI - Phylogeographic relationships in the polypore fungus Pycnoporus inferred from molecular data. AB - The genus Pycnoporus forms a group of four species known especially for producing high redox potential laccases suitable for white biotechnology. A sample of 36 Pycnoporus strains originating from different geographical areas was studied to seek informative molecular markers for the typing of new strains in laboratory culture conditions and to analyse the phylogeographic relationships in this cosmopolitan group. ITS1-5.8S-ITS2 ribosomal DNA and partial regions of beta tubulin and laccase lac3-1 gene were sequenced. Phylogenetic trees inferred from these sequences clearly differentiated the group of Pycnoporus cinnabarinus strains from the group of Pycnoporus puniceus strains into strongly supported clades (100% bootstrap value). Molecular clustering based on lac 3-1 sequences enabled the distribution of Pycnoporus sanguineus and Pycnoporus coccineus through four distinct, well supported clades and sub-clades. A neotropical sub clade, grouping the P. sanguineus strains from French Guiana and Venezuela, corresponded to P. sanguineus sensu stricto. A paleotropical sub-clade, clustering the strains from Madagascar, Vietnam and New Caledonia, was defined as Pycnoporus cf. sanguineus. The Australian clade corresponded to P. coccineus sensu stricto. The Eastern Asian region clade, clustering the strains from China and Japan, formed a P. coccineus-like group. Laccase gene (lac 3-1) analysis within the Pycnoporus species can highlight enzyme functional diversity associated with biogeographical origin. PMID- 22092861 TI - Effect of Bacillus subtilis BsuM restriction-modification on plasmid transfer by polyethylene glycol-induced protoplast fusion. AB - Polyethylene glycol (PEG)-induced cell fusion is a promising method to transfer larger DNA from one cell to another than conventional genetic DNA transfer systems. The laboratory strain Bacillus subtilis 168 contains a restriction (R) and modification (M) system, BsuM, which recognizes the sequence 5'-CTCGAG-3'. To study whether the BsuM system affects DNA transfer by the PEG-induced cell fusion between R(+)M(+) and R(-)M(-) strains, we examined transfer of plasmids pHV33 and pLS32neo carrying no and eight BsuM sites, respectively. It was shown that although the transfer of pLS32neo but not pHV33 from the R(-)M(-) to R(+)M(+) cells was severely restricted, significant levels of transfer of both plasmids from the R(+)M(+) to R(-)M(-) cells were observed. The latter result shows that the chromosomal DNA in the R(-)M(-) cell used as the recipient partially survived restriction from the donor R(+)M(+) cell, indicating that the BsuM R(-)M(-) strain is useful as a host for accepting DNA from cells carrying a restriction system(s). Two such examples were manifested for plasmid transfer from Bacillus circulans and Bacillus stearothermophilus strains to a BsuM-deficient mutant, B. subtilis RM125. PMID- 22092862 TI - Genetic analysis of the pnp-deaD genetic region reveals membrane lipoprotein NlpI as an independent participant in cold acclimatization of Salmonella enterica serovar Typhimurium. AB - The cold acclimatization response in many bacterial species is a tightly regulated process, which ensures the correct folding of macromolecules. In enterobacteria, this response is in part dependent on polynucleotide phosphorylase, which is encoded by the gene pnp. Based on transcriptional analysis of the pnp locus of Salmonella enterica serovar Typhimurium, we show that pnp and the adjacent membrane lipoprotein nlpI gene form an operon with both genes contributing independently to the cold acclimatization response at 15 degrees C. Our findings thereby define a new role for NlpI in bacterial cold acclimatization. PMID- 22092863 TI - Direct and indirect control of Lrp on LEE pathogenicity genes of Citrobacter rodentium. AB - Citrobacter rodentium is a mouse pathogen that, because of its similarities with human enteropathogenic (EPEC) and enterohemorrhagic (EHEC) strains of Escherichia coli is widely used as a model system for in vivo and in vitro studies. Similarly to EPEC and EHEC, C. rodentium carries the LEE (locus of enterocyte effacement) pathogenicity island, encoding virulence factors essential for causing transmissible colonic hyperplasia in mice by attaching and effacing (A/E) lesions. Expression of the genes carried by the LEE pathogenicity island is controlled by complex networks of transcriptional factors, including the global regulators H-NS, IHF, and Fis. In this study, we analyzed the role of Lrp, another global regulator of gene expression in enteric bacteria, on the expression of LEE genes of C. rodentium. To this aim, a real-time PCR approach was used and revealed a negative role of Lrp on the expression of all analyzed LEE genes. Mobility-shift experiments indicated that Lrp action is direct on LEE1 and indirect on all other analyzed LEE genes. PMID- 22092864 TI - Cloning and characterization of a novel cold-active endoglucanase establishing a new subfamily of glycosyl hydrolase family 5 from a psychrophilic deep-sea bacterium. AB - The gene of a novel endo-beta-1,4-glucanase (named Cel5M) was isolated from the psychrophilic deep-sea bacteria Pseudomonas sp. MM15. The deduced protein sequence lacked the typical cellulase domain structures of the carbohydrate binding module and the linker region. Cel5M showed relatively higher activity toward carboxymethyl cellulose, but much lower activity toward p-nitrophenyl-beta D-galactopyranoside and no activity toward avicel. Cel5M was identified as a cold active cellulase with an optimal temperature of 30 degrees C and it was active within a narrow pH range with an optimum at pH 4.5. Phylogenetic analysis showed that Cel5M represented a new subfamily of the glycosyl hydrolase family 5, representing an opportunity for research into and applications of novel cold active cellulases. PMID- 22092865 TI - Comparative genome analysis of Lactococcus garvieae using a suppression subtractive hybridization library: discovery of novel DNA signatures. AB - Lactococcus garvieae, the pathogenic species in the genus Lactococcus, is recognized as an emerging pathogen in fish, animals, and humans. Despite the widespread distribution and emerging clinical significance of L. garvieae, little is known about the genomic content of this microorganism. Suppression subtractive hybridization was performed to identify the genomic differences between L. garvieae and Lactococcus lactis ssp. lactis, its closest phylogenetic neighbor, and the type species of the genus Lactococcus. Twenty-seven clones were specific to L. garvieae and were highly different from Lactococcus lactis in their nucleotide and protein sequences. Lactococcus garvieae primer sets were subsequently designed for two of these clones corresponding to a pyrH gene and a novel DNA signature for application in the specific detection of L. garvieae. The primer specificities were evaluated relative to three previously described 16S rRNA gene-targeted methods using 32 Lactococcus and closely related strains. Both newly designed primer sets were highly specific to L. garvieae and performed better than did the existing primers. Our findings may be useful for developing more stable and accurate tools for the discrimination of L. garvieae from other closely related species. PMID- 22092866 TI - Characterization of four lytic transducing bacteriophages of luminescent Vibrio harveyi isolated from shrimp (Penaeus monodon) hatcheries. AB - Four lytic bacteriophages designated as phiVh1, phiVh2, phiVh3, and phiVh4 were isolated from commercial shrimp hatcheries, possessing broad spectrum of infectivity against luminescent Vibrio harveyi isolates, considering their potential as biocontrol agent of luminescent bacterial disease in shrimp hatcheries, and were characterized by electron microscopy, genomic analysis, restriction enzyme analysis (REA), and pulsed-field gel electrophoresis (PFGE). Three phages phiVh1, phiVh2, and phiVh4 had an icosahedral head of 60-115 nm size with a long, noncontractile tail of 130-329 * 1-17 nm, belonged to the family Siphoviridae. phiVh3 had an icosahedral head (72 +/- 5 nm) with a short tail (27 * 12 nm) and belonged to Podoviridae. REA with DraI and PFGE of genomic DNA digested with ScaI and XbaI and cluster analysis of their banding patterns indicated that phiVh3 was distinct from the other three siphophages. PFGE-based genome mean size of the four bacteriophages phiVh1, phiVh2, phiVh3, and phiVh4 was estimated to be about 85, 58, 64, and 107 kb, respectively. These phages had the property of generalized transduction as demonstrated by transduction with plasmid pHSG 396 with frequencies ranging from 4.1 * 10(-7) to 2 * 10(-9) per plaque-forming unit, suggesting a potential ecological role in gene transfer among aquatic vibrios. PMID- 22092867 TI - Changes of lipid domains in Bacillus subtilis cells with disrupted cell wall peptidoglycan. AB - The cell wall is responsible for cell integrity and the maintenance of cell shape in bacteria. The Gram-positive bacterial cell wall consists of a thick peptidoglycan layer located on the outside of the cytoplasmic membrane. Bacterial cell membranes, like eukaryotic cell membranes, are known to contain domains of specific lipid and protein composition. Recently, using the membrane-binding fluorescent dye FM4-64, helix-like lipid structures extending along the long axis of the cell and consisting of negatively charged phospholipids were detected in the rod-shaped bacterium Bacillus subtilis. It was also shown that the cardiolipin-specific dye, nonyl acridine orange (NAO), is preferentially distributed at the cell poles and in the septal regions in both Escherichia coli and B. subtilis. These results suggest that phosphatidylglycerol is the principal component of the observed spiral domains in B. subtilis. Here, using the fluorescent dyes FM4-64 and NAO, we examined whether these lipid domains are linked to the presence of cell wall peptidoglycan. We show that in protoplasted cells, devoid of the peptidoglycan layer, helix-like lipid structures are not preserved. Specific lipid domains are also missing in cells depleted of MurG, an enzyme involved in peptidoglycan synthesis, indicating a link between lipid domain formation and peptidoglycan synthesis. PMID- 22092868 TI - Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro CT evaluation. AB - OBJECTIVES: To delineate the dynamic micro-architectures of bone induced by low dose bone morphogenetic protein (BMP)-2/7 heterodimer in peri-implant bone defects compared to BMP2 and BMP7 homodimer. MATERIAL AND METHODS: Peri-implant bone defects (8 mm in diameter, 4 mm in depth) were created surrounding SLA treated titanium implants (3.1 mm in diameter, 10 mm in length) in minipig's calvaria. We administrated collagen sponges with adsorbed low-dose (30 ng/mm(3) ) BMP2/7 to treat the defects using BMP2, BMP7 or no BMP as controls.2, 3 and 6 weeks after implantation, we adopted micro-computer tomography to evaluate the micro-architectures of new bone using the following parameters: relative bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), connectivity density, and structure mode index (SMI). Bone implant contact (BIC) was also revealed histologically. RESULTS: Consistent with 2 and 3 weeks, after 6 weeks post-operation, BMP2/7 resulted in significantly higher BV/TV (63.033 +/- 2.055%) and significantly lower SMI ( 4.405 +/- 0.500) than BMP2 (BV/TV: 43.133 +/- 2.001%; SMI: -0.086 +/- 0.041) and BMP7 (BV/TV: 41.467 +/- 1.850%; SMI: -0.044 +/- 0.016) respectively. Significant differences were also found in Tb.N, Tb.Th and Tb.Sp at all time points. At 2 weeks, BMP2/7 resulted in significantly higher BIC than the controls. CONCLUSIONS: Low-dose BMP2/7 heterodimer facilitated more rapid bone regeneration in better quality in peri-implant bone defects than BMP2 and BMP7 homodimers. PMID- 22092869 TI - Reference intervals for hematologic and coagulation tests in adult alpacas (Vicugna pacos). AB - BACKGROUND: Species-specific reference intervals are needed for interpretation of laboratory tests. Reference interval studies of alpacas have been limited by low numbers and use of outdated methods. OBJECTIVES: The aims of this study were to establish reference intervals for hematologic and coagulation tests in alpacas using a laser-based hematology analyzer and a mechanical clot detection coagulation analyzer, respectively; to compare results for automated and manual differential WBC and platelet counts and fibrinogen concentrations; and to examine the effect of herd and sex on hematologic tests in a population of alpacas. METHODS: Blood collected from clinically healthy female and male adult alpacas (Vicugna pacos) from 5 herds underwent full CBC analysis using an ADVIA 2120 (n = 65). Blood smears were examined for manual differential WBC counts, platelet estimates, and morphologic examination of blood cells. PCV and plasma protein and heat-precipitable fibrinogen concentration measured by refractometry were also determined. Partial thromboplastin time, prothrombin time, and clottable fibrinogen concentration were measured using a STA Compact analyzer (n = 13). Reference intervals were established using 2.5th and 97.5th percentiles for hematologic analytes and minimum and maximum values for coagulation tests. Automated and manual differential WBC counts, platelet counts, and fibrinogen concentrations were compared. Results were also evaluated for herd- and sex associated effects. RESULTS: Hematologic reference intervals for alpacas were similar to those reported previously, except for lower RBC-related results, which showed a herd bias. Correlations between automated and manual neutrophil, lymphocyte, eosinophil, and platelet counts were moderate to good, with weak to poor correlations for monocyte and basophil counts and fibrinogen concentrations. Owing to the low number of samples analyzed, reference intervals for coagulation tests should be considered estimated intervals. CONCLUSIONS: Reference intervals will be useful guides for interpreting hematologic and coagulation results in alpacas, particularly when using the same instrumentation and reagents. PMID- 22092870 TI - Assessment of human exposure to indoor organic contaminants via dust ingestion in Pakistan. AB - Ingestion of indoor dust has been acknowledged as an important route of exposure to organic contaminants (OCs). We investigated the presence of polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), organophosphate flame retardants (OPFRs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) in indoor floor dust from rural homes (N=31) and mosques (N=12) in Gujrat, Pakistan. Low concentrations were observed for most contaminants. OPFRs were the principle contaminants, with tri (2-butoxyethyl)-phosphate (TBEP) and tri-phenyl-phosphate (TPP) having medians of 66 and 109 ng/g, respectively. PBDEs were only minor constituents in the investigated samples, with BDE 209 (median 40 ng/g) being the most important congener. Levels and profile of ?PBDEs, ?NBFRs, ?HCHs, ?DDTs, and ?PCBs revealed no difference (P<0.05) between samples of dust from homes and mosques, indicating similar emission sources. Exposure scenarios using 5th percentile, median, mean, and 95th percentile levels were estimated for both adult and toddlers. Typical high-end, using median levels and high dust ingestion, exposure for adults were 0.02, 0.02, 0.03, <0.01, and 0.65 ng/kg bw/day and for toddlers 0.39, 0.45, 0.69, 0.01, and 15.2 ng/kg bw/day for ?PBDEs, ?NBFRs, ?OCPs, ?PCBs, and ?OPFRs, respectively. To the authors' knowledge, this is the first study to document the presence of indoor OCs in Pakistani dust. PRACTICAL IMPLICATIONS: This is the first report on the analysis of various contaminants in indoor dust from Pakistan. Some of these chemicals are currently being used in different consumer products. The study will help to further an understanding of the levels of different organic contaminants (OCs) in Pakistani indoor environments and will enlighten the generally ignored area of environmental pollution in Pakistan. Furthermore, studies based on animal models have shown that some of the analyzed chemicals can cause different types of chronic toxicities. However, our results showed that the levels of estimated exposure via dust ingestion for all chemicals were several orders of magnitude lower than their reference dose (RfD) values or than those reported in studies from Belgium, China, Singapore, and the UK (Ali et al., 2011a; Harrad et al., 2008; Tan et al., 2007a,b; Van den Eede et al., 2011a; Wang et al., 2010). PMID- 22092871 TI - Production of viruses during a spring phytoplankton bloom in the South Pacific Ocean near of New Zealand. AB - Lagrangian studies of virus activity in pelagic environments over extended temporal scales are rare. To address this, viruses and bacteria were examined during the course of a natural phytoplankton bloom in the pelagic South Pacific Ocean east of New Zealand. Daily samples were collected in a mesoscale eddy from year days 263-278 (September 19th-October 4th, 2008). The productive bloom transitioned from a diatom to a pico- and nanoplankton-dominated system, resulting in chlorophyll a concentrations up to 2.43 MUg L(-1) . Virus abundances fluctuated c. 10-fold (1.8 * 10(10) -1.3 * 10(11) L(-1) ) over 16 days. The production rates of virus particles were high compared with those reported in other marine systems, ranging from 1.4 * 10(10) to 2.1 * 10(11) L(-1) day(-1) . Our observations suggest viruses contributed significantly to the mortality of bacteria throughout the bloom, with 19-216% of the bacterial standing stock being lysed daily. This mortality released nutrient elements (N, Fe) that likely helped sustain the bloom through the sampling period. Parametric analyses found significant correlations with both biotic (e.g. potential host abundances) and abiotic parameters (e.g. nutrient concentrations, temperature). These observations demonstrate that viruses may be critical in the extended maintenance of regeneration-driven biological production. PMID- 22092872 TI - Interleukin-4 and interleukin-13 prime migrational responses of haemopoietic progenitor cells to stromal cell-derived factor-1alpha. AB - BACKGROUND: Lung-homing of progenitor cells is associated with inflammatory and remodelling changes in asthma. Factors that modulate the increased traffic of progenitor cells to the site of inflammation in asthma remain to be defined. Interleukin (IL)-4 and IL-13 are Th2 cytokines that are key regulators of asthma pathology. OBJECTIVE: We investigated the role of IL-4 and IL-13 in modulating the trans-migrational responses of haemopoietic progenitor cells (HPC). METHODS: HPC were enriched from cord blood (CB) and peripheral blood (PB) samples. Migration of HPC was assessed using transwell migration assays, and responding cells were enumerated by flow cytometry. RESULTS: IL-4 and IL-13 primed migration of CB- and PB-derived HPC (CD34(+) 45(+) cells) to stromal cell-derived factor 1alpha (SDF-1alpha), in vitro. However, these cytokines had no effect on migrational responses of eosinophil-lineage committed progenitors (CD34(+) 45(+) IL-5Ralpha(+) cells) or mature eosinophils to SDF-1alpha. For HPC, priming effects of IL-4 (0.1 ng/mL) and IL-13 (0.1 ng/mL) were detectable within 1 h and optimal at 18-h post-incubation, and IL-4 was the more effective priming agent. Pre-incubation with IL-4 or IL-13 had no effect on the intensity of cell surface expression of SDF-1alpha receptor, CXCR4. Disruption of cell membrane cholesterol content by pre-incubation with polyene antibiotics inhibited IL-4 priming of SDF 1alpha stimulated migration of HPC indicating that increased incorporation of CXCR4 into membrane lipid rafts mediated the cytokine primed migrational response of HPC. This was confirmed by confocal fluorescent microscopy. CONCLUSIONS AND CLINICAL RELEVANCE: IL-4 and IL-13 prime the migrational response of HPC to SDF 1alpha by enhancing the incorporation of CXCR4 into lipid rafts. The priming effect of these cytokines is specific to primitive HPC. These data suggest that increased local production of IL-4 and IL-13 within the lungs may promote increased SDF-1alpha mediated homing of HPC to the airways in asthma. PMID- 22092873 TI - Variation in arterial supply to the floor of the mouth and assessment of relative hemorrhage risk in implant surgery. AB - OBJECTIVES: Bleeding in the floor of the mouth during implant surgery is attributed to arterial injuries in the sublingual space: clinicians may injure the submental and sublingual arteries, which originate from the facial and lingual arteries, respectively. This study aimed to clarify the three-dimensional courses of submental and sublingual arteries and their topographic relation to the mandible. MATERIALS AND METHODS: During the gross anatomy course at the Faculty of Dentistry and Graduate School, Niigata University (2009-2011), we investigated the relationship between the courses of submental and sublingual arteries and their dividing patterns of the mylohyoid muscle, sublingual gland, and mandible using 27 human cadavers. RESULTS: The courses of submental and sublingual arteries were divided into four patterns: (1) the sublingual space was supplied by the sublingual artery (type I: 63%), (2) it was supplied by both the sublingual and submental arteries (type II: 5.6%), (3) it was supplied by the submental artery without the sublingual artery (type III: 29.6%), and (4) type III without the deep lingual artery originated from the lingual artery (type IV: 1.8%). In type II, III, and IV, the submental artery perforates the mylohyoid muscle or takes a roundabout route to travel near the surface of the mandible. The percentage occurrence of arteries traveling between the sublingual gland and mandible in type II, III, and IV (55%) is higher than that in type I (8.8%). CONCLUSION: Susceptibility of the submental artery in type II, III, and IV to injury during implant surgery is suggested. PMID- 22092874 TI - Octreotide as therapeutic option for congenital idiopathic chylothorax: a case series. AB - BACKGROUND: Octreotide, a somatostatin analogue, is used for the management of patients with refractory chylothorax although its safety and efficacy in neonates have not been evaluated in controlled clinical trials. We present one of the largest case series about the use of octreotide in congenital idiopathic chylothorax. METHODS: Six cases of congenital chylothorax (CC) were prospectively collected, who were managed with same unit protocol for octreotide. Mean (SD) gestation was 34.5 (+/-2.2) weeks, and birthweight was 3410 (+/-840.4) g. All infants required chest drains from day 1 of life, and the mean (SD) duration of insertion was 36.1 (+/-8.5) days. Octreotide was commenced at a median age of 13.5 days (range 8-22), given for a median duration of 20 days (range 12-27). The starting dose was 0.5-1 MUg/kg/h with an increment of 1-2 MUg/kg/day to a maximum of 10 MUg/kg/day. Resolution of chylothorax was achieved in five patients, being resistant to treatment in the sixth patient. None had adverse effects from octreotide. Full enteral feeds were reached at a mean age of 44 days. CONCLUSION: Early commencement of octreotide is recommended although further reports to evaluate the safety and efficacy would add to the profile of this medication in the treatment of CC. PMID- 22092875 TI - Effect of thread size on the implant neck area: preliminary results at 1 year of function. AB - OBJECTIVES: To evaluate and compare the effect of the coronal thread size on the marginal bone loss around the fixtures, when both implants were provided with threads to the top of fixture. MATERIALS AND METHODS: Two groups of implants, one with a macro-thread to the top of the fixture (A) and the other with a micro thread to the top of the fixture (B), were placed adjacent to each other in the partially edentulous areas of 20 patients. Bone loss around each implant was analyzed after 1 year of functional loading. The bone losses after loading were compared using Wilcoxon's signed-rank test. RESULTS: The mean marginal bone losses (A, 0.154 +/- 0.144 mm; B, 0.125 +/- 0.136 mm) were not statistically significant between the two groups (P = 0.669). CONCLUSIONS: There was no significant difference between implant with macro- and micro-neck thread in terms of marginal bone loss after 1 year of loading. PMID- 22092876 TI - Engineering of a periodontal ligament construct: cell and fibre alignment induced by shear stress. AB - AIM: We report an in vitro technique to establish alignment of collagen fibres and cells within a three-dimensional tissue equivalent that mimics the natural periodontal ligament (PDL) using a novel custom-designed bioreactor. MATERIAL AND METHODS: Shear stress was applied to the tissue equivalent prepared with collagen solution and seeded with human PDL cells. Stress-strain dynamics and the alignment of collagen fibres and PDL cells in tissue equivalents were analysed. RESULTS: Shear stress aligned collagen fibres and PDL cells in a direction parallel to the principle strain vector. PDL cells and Collagen fibres aligned in strained tissue equivalents with higher uniformity than in unstrained tissue equivalents. CONCLUSIONS: The cell and fibre alignment of the engineered PDL was precisely guided by mechanical shear stress along the direction of principal strain vector using a custom-designed bioreactor, suggesting that the enhanced functional property of engineered PDL constructs could be achieved with this technique. PMID- 22092877 TI - My eyes, your eyes--the relationship between CMS five-star rating of nursing homes and family rating of experience of care in Maryland. AB - In 2008, the Centers for Medicaid and Medicare Services (CMS) launched the Five Star Quality Rating System to help consumers compare nursing homes. The quality rating system consists of three domains: nursing home inspection results, staffing, and quality measures (QMs) and an overall rating calculated from the three domains. The Five-Star System has both advocates and detractors. One source of criticism about the rating system is its lack of input from consumer surveys. Although different dimensions of quality have been recognized as important by the experts and studied in the literature, how these dimensions are linked with each other is largely unknown. This article describes an analysis of the relationship between overall experience of care ratings from a family survey and ratings obtained on the CMS Five-Star Quality Rating for Maryland nursing homes. The results indicated a strong positive correlation between family experience of care score and two five-star domains, namely health inspections and nurse staffing, and no relationship with the quality domain. The lack of relationship between the quality domain and the family score may be due to inadequate risk adjustment or that each rating system measures different aspects of quality. PMID- 22092878 TI - Autologous fibroblast culture in the repair of aging skin. AB - BACKGROUND: Human cell cultures are being developed to replace various body tissues. OBJECTIVE: To assess the safety and efficacy of dermal regeneration with the injection of young autologous fibroblasts obtained from culture containing serum from patients themselves. MATERIALS AND METHODS: Dermal tissue from the groin of five patients was cultivated in M199 medium supplemented with 10% human serum. Four population doublings were obtained. The fibroblasts were injected intradermally into forehead wrinkles and periorbital and paranasal areas. RESULT: At the fourth population doubling, a mean of 3.85 * 10(6) cells/mL was obtained; viability was 98%. Sixty days after completing treatment, with four injections given at 15-day intervals, periorbital tonicity had improved significantly, although the quantity of fibroblasts used resulted in little improvement to surface lines and no improvement at all in deeper wrinkles. After 6 months, no further changes were found beyond the initial results obtained. CONCLUSION: Injection of skin fibroblasts cultivated in medium supplemented with human serum is a viable technique and provokes no side effects. Four injections given at 15 day intervals containing a total of 6.4 * 10(6) fibroblasts/mL resulted in significant improvement in periorbital skin flaccidity. Further studies should be conducted with larger sample sizes. PMID- 22092880 TI - Cancer survivors' experiences of discharge from hospital follow-up. AB - Discharge from hospital follow-up is a key time point in the cancer journey. With recommendations for earlier discharge of cancer survivors, attention to the discharge process is likely to become increasingly important. This study explored cancer survivors' experiences of discharge from hospital follow-up. Survivors of breast, colorectal and prostate cancer (n= 1275), 5-16 years post diagnosis were approached to take part in a questionnaire survey. The questionnaire included questions about discharge status, provision of time/information prior to discharge, feelings at discharge and satisfaction with how discharge was managed. Completed questionnaires were returned by 659 survivors (51.7%). Approximately one-third of respondents were not discharged from follow-up 5-16 years post diagnosis. Of those discharged, a substantial minority reported insufficient time (27.9%), information (24.5-45.0%) or adverse emotions (30.9%) at the time of discharge. However, 90.6% of respondents reported satisfaction with how discharge from hospital follow-up was managed. Despite high levels of satisfaction, discharge of cancer survivors from hospital follow-up could be improved with the provision of additional time, information and support. Better structuring of the final hospital appointment or a review appointment in primary care at this time could help to ensure that discharge from hospital follow-up is managed optimally for cancer survivors. PMID- 22092879 TI - Phylogenetic relationship of Lotus uliginosus symbionts with bradyrhizobia nodulating genistoid legumes. AB - Lotus species are legumes with potential for pastures in soils with low-fertility and environmental constraints. The aim of this work was to characterize bacteria that establish efficient nitrogen-fixing symbiosis with the forage species Lotus uliginosus. A total of 39 isolates were obtained from nodules of L. uliginosus naturally growing in two different locations of Portugal. Molecular identification of the isolates plus the commercial inoculant strain NZP2039 was performed by REP-PCR, 16S rRNA RFLP, and 16S rRNA, glnII and recA sequence analyses. Limited genetic diversity was found among the L. uliginosus symbionts, which showed a close phylogenetic relationship with the species Bradyrhizobium japonicum. The symbiotic nifH, nodA and nodC gene sequences were closely related with the corresponding genes of various Bradyrhizobium strains isolated from Lupinus and other genistoid legumes and therefore were phylogenetically separated from other Lotus spp. rhizobia. The L. uliginosus bradyrhizobia were able to nodulate and fix nitrogen in association with L. uliginosus, could nodulate Lotus corniculatus with generally poor nitrogen-fixing efficiency, formed nonfixing nodules in Lotus tenuis and Lupinus luteus roots and were unable to nodulate Glycine soja or Glycine max. Thus, L. uliginosus rhizobia seem closely related to B. japonicum biovar genistearum strains. PMID- 22092881 TI - Dynamic analysis for mental sweating of a group of eccrine sweat glands on a human fingertip by optical coherence tomography. AB - BACKGROUND: An important function of skin physiology is mental sweating, where sweating is accelerated via the sympathetic nerve by mental or physical stress externally applied to a volunteer. AIM: Activity of the sympathetic nerve (ASN) is evaluated by quantitative measurement of mental sweating. MATERIAL AND METHODS: Optical coherence tomography (OCT) is highly potential for in vivo observation of human sweating dynamics which affects ASN. We demonstrate dynamic OCT analysis of mental sweating of a group of eccrine sweat glands. The sweating dynamics is tracked simultaneously for 19 sweat glands by time-sequential piled up en-face OCT images with the frame spacing of 3.3 s. The en-face OCT images of the spiral lumen of the eccrine sweat gland are constructed by data acquisition of the 128 B-mode OCT images. RESULTS: It is thus found that the response to mental stress is different for each sweat gland even though the sweat glands are adjacent to each other. Such strong non-uniformity is observed in mental sweating where the amount of excess sweat is different for each sweat gland although the sweat glands are adjacent to each other. DISCUSSION: The non-uniformity should be necessary to adjust as precisely the total amount of excess sweat as possible through the sympathetic nerve in response to strength of the stress. PMID- 22092882 TI - Cardiac electromechanical delay is increased during recovery from 40 km cycling but is not mediated by exercise intensity. AB - Cardiac electrical-mechanical delay (cEMD), left ventricular (LV) function, and cardiac troponin I (cTnI) were assessed after 40 km cycle time trials completed at high (HIGH) and moderate (MOD) intensities in 12 cyclists. Echocardiograms and blood samples were collected before, 10, and 60 min after cycling. cEMD as assessed by time from QRS onset to peak systolic (S') tissue velocity was lengthened after both bouts of cycling but was not mediated by cycling intensity (HIGH: 174 +/- 52 vs 198 +/- 26 ms; MOD: 151 +/- 40 vs 178 +/- 52 ms, P < 0.05). Global LV systolic function was unaltered by exercise. cEMD from QRS to peak early (E') diastolic tissue velocity was also increased post-exercise (HIGH: 524 +/- 95 vs 664 +/- 68 ms; MOD: 495 +/- 62 vs 604 +/- 91 ms, P < 0.05). Indices of LV diastolic function was reduced after cycling but were not mediated by exercise intensity. cTnI was elevated in two participants after HIGH trial (0.06 ug/L; 0.04 ug/L) and one participant after MOD trial (0.02 ug/L). While cEMD is lengthened and LV diastolic function was reduced post-cycling, altering time trial intensity had little impact upon cEMD, LV function, and cTnI release. PMID- 22092883 TI - Obesity is associated with increased asthma severity and exacerbations, and increased serum immunoglobulin E in inner-city adults. AB - BACKGROUND: Obesity is associated with increased asthma and atopy. OBJECTIVE: To determine whether or not obesity in inner-city adults is associated with increased asthma prevalence, severity and exacerbations and IgE responses. METHODS: This retrospective study involved 246 adults with asthma and other atopic disorders who were seen at an asthma clinic in New York City between 1997 and 2010. Height, weight, asthma diagnosis and symptoms, peak flow (PF), spirometry, serum IgE levels and white blood cell differentials were recorded. RESULTS: Asthmatic patients had higher body mass index than non-asthmatics (median, interquartile range: 30.5, 10.2 vs. 27.8, 8.8; Mann-Whitney U-test, P = 0.0006). Class I and II/III obesity were associated with increased asthma (I: OR: 2.35, 95% CI: 1.04-5.34, P = 0.04; II/III: OR: 3.25, 95% CI: 1.36-7.74, P = 0.008). Class I and II/III obesity were associated with worsened asthma severity (ordinal logistic regression; I: OR: 4.23, 95% CI: 1.61-11.06, P = 0.003; II/III: OR: 2.76, 95% CI: 1.08-7.09, P = 0.03). Class II/III obesity was associated with increased asthma exacerbations requiring oral corticosteroids (repeated measures logistic regression, OR: 1.13, 95% CI: 1.03-1.25; P = 0.01) and increased requirement of inhaled corticosteroid for long-term asthma management (OR: 1.45, 95% CI: 1.29-1.62; P < 0.0001). In asthmatics, class II/III obesity was associated with decreased PF (general linear model, least squares mean +/- SEM: 333.8 +/- 37.4 vs. 396.2 +/- 32.1 L/min; P = 0.007), forced expiratory volume in 1 s (75.2 +/- 4.6 vs. 88.4 +/- 5.6%; P = 0.03) and forced vital capacity (83.2 +/ 4.7 vs. 109.2 +/- 6.0%; P = 0.0002) and increased serum IgE (480.2 +/- 88.3 vs. 269.0 +/- 66.6 IU/mL; P = 0.04) and neutrophils (66.6 +/- 3.7 vs. 60.1 +/- 3.8%; P = 0.02). Class I obesity was also associated with increased serum IgE (458.7 +/ 68.9, P = 0.03). CONCLUSION AND CLINICAL RELEVANCE: Obesity in inner-city adults may be both a risk and exacerbating factor for atopic asthma. PMID- 22092884 TI - The trigeminocardiac reflex and dermatologic surgery. PMID- 22092885 TI - Atlas-based versus individual-based fiber tracking of the corpus callosum in patients with multiple sclerosis: reliability and clinical correlations. AB - BACKGROUND AND PURPOSE: In multiple sclerosis (MS), the presence of lesions and normal-appearing white matter damage may affect the reliability of diffusion tensor (DT) magnetic resonance imaging (MRI)-based tractography. We compared the performance of an individual-based method for corpus callosum (CC) fiber tracking in MS with those of two atlas-based methods. METHODS: Brain DT MRI scans were acquired from 35 patients with MS and 18 age-matched healthy volunteers (HV). DT derived metrics from the CC-the mean diffusivity (MD) and fractional anisotropy (FA)-were calculated using an individual-based and two atlas-based methods with different types of subject registration (linear and nonlinear) to a CC atlas. Customized termination criteria were applied to stop the tracking algorithm when using the individual-based method. RESULTS: All the methods were able to distinguish between MS patients and HV. Using the individual-based method, stronger relationships were found between CC DT-derived metrics and the subjects' clinical condition. CONCLUSION: CC DT tractography using an individual-based method is more sensitive than the atlas-based ones to tract-specific alterations related to MS disability. An atlas-based method with nonlinear registration can be a valid alternative when an automated postprocessing is warranted, such as in the case of high volumes of data. PMID- 22092886 TI - High prevalence of shoulder pain among elite Norwegian female handball players. AB - Clinical experience indicates that a substantial number of handball players may suffer from shoulder pain, but they continue to play despite having shoulder pain problems. The aim of this study was to evaluate the prevalence and consequences of shoulder pain problems among Norwegian female elite handball players. In the preseason of the 2007-2008 season, 179 players from all 12 teams of the Norwegian elite league went through the following tests: internal and external shoulder range of motion, apprehension, relocation test, and shooting velocity. All players completed the Fahlstrom questionnaire and, for players with current pain, the Western Ontario shoulder instability index questionnaire. Sixty-five (36%) players reported shoulder pain on the test day, and 40 (22%) players reported previous shoulder pain. Two thirds of the players with pain reported a gradual onset. For players with current or previous pain, 22 (36%) and 14 (36%) had missed match play, and 43 (68%) and 28 (76%) reported changing their training habits. A positive apprehension and relocation test was found among 51 (29%) of the players. In conclusion, a high proportion of female elite handball players experience shoulder pain and problems and have an unstable shoulder. PMID- 22092887 TI - Are marginal bone levels and implant stability/mobility affected by single-stage platform switched dental implants? A comparative clinical study. AB - OBJECTIVES: The aim of this study was to evaluate short-term bone level and stability/mobility measurement alterations at platform switched (PS) and standard platform (SP) implants placed in mandibular premolar/molar regions using a single stage protocol. MATERIALS AND METHODS: Sixteen PS and 16 SP implants restorated with fixed prosthesis were included. Standard implant dimensions were used for both implant systems. After 3 months of osseointegration, implants were connected to abutments and final restorations were performed. Marginal bone loss was measured by standardized periapical radiographs. Implant stability/mobility was determined by resonance frequency analysis (RFA) and mobility measuring (MM) device values. Peri-implant parameters were evaluated with clinical periodontal indices and all parameters were assessed at baseline, 1, 3, and 6 months after the surgery. RESULTS: After 6 months, all implants showed uneventful healing. Radiographic evaluation showed a mean bone loss of 0.72 mm for PS and 0.56 mm for SP implants, and there were no significant differences between implant types. At 6 months, mean implant stability quotient (ISQ) values were 73.38 and 77 for PS and SP implants, respectively. Mean MM values were -4.75 for PS and -6.38 for SP implants. Mean MM values were lower for SP implants compared to PS implants at all time points. No significant differences were detected between implant types according to clinical peri-implant parameters. CONCLUSIONS: The micro-gap at crestal level which immediately exposed to the oral cavity in non-submerged two part implants seems to have adverse influence on the marginal bone level. PMID- 22092888 TI - Signal integration by the Cpx-envelope stress system. AB - The Cpx-envelope stress system coordinates the expression and assembly of surface structures important for the virulence of Gram-negative pathogenic bacteria. It is comprised of the membrane-anchored sensor kinase CpxA, the cytosolic response regulator CpxR and the accessory protein CpxP. Characteristic of the group of two component systems, the Cpx system responds to a broad range of stimuli including pH, salt, metals, lipids and misfolded proteins that cause perturbation in the envelope. Moreover, the Cpx system has been linked to inter-kingdom signalling and bacterial cell death. However, although signal specificity has been assumed, for most signals the mechanism of signal integration is not understood. Recent structural and functional studies provide the first insights into how CpxP inhibits CpxA and serves as sensor for misfolded pilus subunits, pH and salt. Here, we summarize and reflect on the current knowledge on signal integration by the Cpx-envelope stress system. PMID- 22092889 TI - Anatomic variations and lesions of the maxillary sinus detected in cone beam computed tomography for dental implants. AB - OBJECTIVE: To evaluate the presence of anatomic variations and lesions of the maxillary sinus in cone beam computed tomography (CBCT) of the maxilla required for dental implant planning. MATERIAL AND METHODS: This transversal prevalence study evaluated a sample of 500 consecutive CBCT exams. The inclusion criteria were CBCT exams of the maxilla required for dental implant planning. The CBCT exams were independently evaluated by two oral and maxillofacial radiologists who assessed the presence of anatomic variations and lesions of the maxillary sinus. As most of the CBCT exams did not allow the evaluation of the area close to the maxillary sinus roof, anatomic variations that take place at this site were not assessed. RESULTS: The anatomic variations detected were pneumatization (83.2%), antral septa (44.4%), hypoplasia (4.8%), and exostosis (2.6%). The identified lesions were mucosal thickening (<=3 mm in 54.8% and >3 mm in 62.6%), polypoid lesions (21.4%), discontinuity of the sinus floor (17.4%), air-fluid level (4.4%), bone thickening of the maxillary sinus wall (3.8%), antroliths (3.2%), discontinuity of the sinus lateral wall (2.6%), sinus opacification (1.8%), and foreign body (1.6%). CONCLUSION: Anatomic variations and lesions of the maxillary sinus were common findings in CBCT exams of the maxilla required for dental implant planning. As some of these conditions can modify dental implant planning and must require specialized treatment, its recognition is noteworthy in dental practice, and especially in implantology. The amount and significance of the anatomic variations and lesions detected in this study reinforces the importance of computed tomography in preoperative dental implant planning. PMID- 22092890 TI - Evaluation of the catalase promoter for expressing the alkaline xylanase gene (alx) in Aspergillus niger. AB - Aspergillus niger represents a promising host for the expression of recombinant proteins, but only a few expression systems are available for this organism. In this study, the inducible catalase promoter (PcatR) from A. niger was characterized. For this, constructs were developed and checked for the expression of the alkaline xylanase gene transcriptionally fused under the cat R promoter. Two versions of the catalase (catR) promoter sequence from A. niger (P(cat300,) P(cat924)) were isolated and tested for their ability to drive expression of the alkaline xylanase (alx) gene. P(cat924) showed better efficiency (more than 10 fold increase in AlX activity compared to P(cat300)) under the optimized culture conditions. Induction of the catR promoter with 0.20% H(2)O(2) and 1.5% CaCO(3) in the culture medium, further increased expression of AlX 2.61- and 2.20-fold, respectively, clarifying its inducible nature. Specific induction or repression of the catR promoter provides the possibility for utilization of this promoter in heterologous protein production. PMID- 22092891 TI - Do we need to reconsider the desirable blood level of vitamin B12? PMID- 22092892 TI - The low rate of bacterial meningitis in children, ages 6 to 18 months, with simple febrile seizures. AB - OBJECTIVES: This evidence-based review examines the risk of bacterial meningitis as diagnosed by lumbar puncture (LP) in children presenting to the emergency department (ED) with a simple febrile seizure. The study population consists of fully immunized children between ages 6 and 18 months of age with an unremarkable history and normal physical examination. METHODS: MEDLINE, EMBASE, and Cochrane Library databases were searched for studies that enrolled children who presented with simple febrile seizure to the ED and had LP performed to rule out meningitis. The primary outcome measure was the risk of bacterial meningitis based on findings of the LP. The secondary outcome was the rate of cerebrospinal fluid (CSF) pleocytosis in children who were pretreated with antibiotics. RESULTS: Two studies enrolling a total of 150 children met the inclusion and exclusion criteria. The overall rate of meningitis was 0% (95% confidence interval [CI] = 0.0% to 3.0%). The rate of CSF pleocytosis in children who were pretreated with antibiotics was 2.5% (95% CI = 0.0% to 14.0%). CONCLUSIONS: The sample size of the studies included in this review is too small to draw any definitive conclusion. However, their findings suggest that that the risk of bacterial meningitis in children presenting with simple febrile seizure is very low. PMID- 22092893 TI - Validation and refinement of the difficult intravenous access score: a clinical prediction rule for identifying children with difficult intravenous access. AB - OBJECTIVES: The difficult intravenous access (DIVA) score, a proportionally weighted four-variable (vein palpability, vein visibility, patient age, and history of prematurity) clinical rule, has been developed to predict failure of intravenous (IV) placement in children. This study sought to externally validate and refine the DIVA score. METHODS: Patients undergoing peripheral IV placement by pediatric emergency department (ED) nurses were enrolled. The outcome of interest was defined as failure of cannulation on first attempt. Proposed refinement predictor variables include history of newborn intensive care unit (NICU) stay, operator experience characteristics (years since graduation, years of pediatric nursing experience, and IVs started per month), and skin shade. Adjusted multivariate models were constructed using logistic regression. Receiver operating characteristic (ROC) curves were constructed and areas under the curve (AUC) calculated for each model. RESULTS: A total of 366 subjects were enrolled (mean age = 5.4 years, SD +/- 5.6 years) and of them, 118 (32.2%) subjects failed the first IV attempt. The original four-variable model tested in this data set resulted in an AUC of 0.72 (95% confidence interval [CI] = 0.67 to 0.78). Patients with a DIVA score of 4 or greater had more than 50% likelihood of failed first IV attempt. A three-variable rule (vein palpability, vein visibility, and patient age) was evaluated and found to possess similar discriminating ability (AUC = 0.72, 95% CI = 0.67 to 0.78). CONCLUSIONS: This study validated the previously derived four-variable DIVA score. A simpler three-variable rule was as predictive of failed IV placement on first attempt as the four-variable rule. Validation in nonpediatric EDs is needed to thoroughly evaluate generalizability. PMID- 22092894 TI - L-carnitine increases survival in a murine model of severe verapamil toxicity. AB - OBJECTIVES: L-carnitine is an essential compound involved in cellular energy production through free fatty acid metabolism. It has been theorized that severe verapamil toxicity "shifts" heart energy production away from free fatty acids and toward other sources, contributing to profound cardiogenic shock. The primary study objective was to determine whether intravenous (IV) L-carnitine affects survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic parameters. The authors hypothesized that IV L-carnitine would increase both survival and hemodynamic parameters in severe verapamil toxicity. METHODS: This was a controlled, blinded animal investigation. Sixteen male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate. Verapamil toxicity was achieved by a constant infusion of 5 mg/kg/hr. After 5 minutes a bolus of 50 mg/kg of either L-carnitine or normal saline was given. The experiment concluded when either 10% of baseline MAP was achieved or 150 minutes had elapsed. The data were analyzed using Kaplan Meier analysis, log rank test, and analysis of variance. RESULTS: The median survival for the animals in the L-carnitine group was 140.75 minutes (interquartile range [IQR] = 98.6 to 150 minutes), and for those in the normal saline group it was 49.19 minutes (IQR = 39.02 to 70.97 minutes; p = 0.0001). At 15 minutes the MAP was 20.45 mm Hg greater in the animals in the L-carnitine group than in the animals in the normal saline group (95% confidence interval [CI] = 0.25 to 40.65; p = 0.047). CONCLUSIONS: When compared with saline, IV L carnitine increases survival and MAP in a murine model of severe verapamil toxicity. PMID- 22092895 TI - Levamisole exposure and hematologic indices in cocaine users. AB - OBJECTIVES: Levamisole is an antihelminthic agent found in nearly 70% of seized U.S. cocaine. Sporadic case literature describes a life-threatening agranulocytosis associated with levamisole exposure secondary to cocaine use. The authors compared the distribution of hematologic indices in a population of cocaine users with and without a confirmed exposure to levamisole. METHODS: The records of all patients in the Lifespan hospital system who underwent comprehensive toxicologic testing between September 2009 and December 2009 (n = 799) were reviewed. Of these, 95 patients were eligible for inclusion (cocaine positive with a simultaneous complete blood count). Patients were grouped into levamisole-positive (n = 47) and -negative (n = 48) groups. The primary outcome measures were total white blood cell count (WBC), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC); secondary outcome measures included percent neutrophils, lymphocytes, eosinophils, monocytes, and basophils, as well as identified co-ingestants. RESULTS: Both groups had a similar makeup of age, sex, and race. The total WBC count, ANC, and ALC were not significantly different between the two groups. There was no significant difference in relative proportion of neutrophils, eosinophils, basophils, or monocytes between the groups. There was one neutropenic patient in the levamisole-positive group, while three patients were neutropenic in the negative group. Additionally, a literature review of case reports describing levamisole-induced agranulocytosis (n = 33) was conducted. In 52% of these cases, patients presented with an oropharyngeal chief complaint; in an additional 27%, patients presented with soft tissue infections or purpura. CONCLUSIONS: The overall incidence of neutropenia was 4.2% in all cocaine users and 2.1% in the levamisole-positive group. A striking number of the reported patients with levamisole-associated neutropenia have presented to care with oropharyngeal complaints, vasculitis, or fever. A clinical algorithm for identifying levamisole toxicity in the emergency department setting is provided. Further research is necessary to determine the circumstances required for levamisole-associated neutropenia. PMID- 22092896 TI - Short, subjective measures of numeracy and general health literacy in an adult emergency department. AB - OBJECTIVES: The objective was to evaluate the reliability and validity of brief subjective measures of numeracy and general health literacy in the adult emergency department (ED) setting. METHODS: A convenience sample of adult ED patients completed subjective measures of general health literacy (Short Literacy Survey [SLS]) and numeracy (Subjective Numeracy Scale [SNS]). These patients also completed two objective tests of literacy (the Short Test of Functional Health Literacy in Adults [S-TOFHLA] and the Rapid Estimate of Adult Literacy in Medicine [REALM]) and an objective test of numeracy (Wide Range Achievement Test 4 [WRAT4]). Internal reliability of the subjective measures was assessed using Cronbach's alpha. Construct validity of the subjective measures was assessed by correlating them against the S-TOFHLA, REALM, and WRAT4, using Spearman's rank correlation coefficients, receiver operating characteristics (ROC) curves, and hierarchical, multiple linear regression with adjustment for patient age, sex, race, and education. RESULTS: The median age of the 207 patients surveyed was 46 years (interquartile range [IQR] = 32 to 59 years); 27% were African American. Sixty-one percent of patients reported that their highest level of education was high school or below. As measured by the S-TOFHLA and REALM, most patients had adequate literacy levels (89% and 80%, respectively), while 44% of patients had below average numeracy skills on the WRAT4. The median SLS score was 14 (IQR = 12 to 15) on a scale of 3 to 15; the median SNS score was 36 (IQR = 30 to 42) on a scale of 6 to 48. The SLS and SNS had good internal reliability, with Cronbach's alphas of 0.74 and 0.82, respectively. The SLS Spearman's rank order correlation coefficient was 0.33 (95% confidence interval [CI] = 0.20 to 0.45) for the S TOFHLA, with a standardized beta coefficient of 0.36 (p < 0.05) after adjustment for patient demographics. The SLS correlation coefficient was 0.26 (95% CI = 0.13 to 0.38) for the REALM, with a standardized beta coefficient of 0.38 (p < 0.05) after adjustment for patient demographics. The area under the ROC curve (AUC) for the SLS was 0.74 (95% CI = 0.68 to 0.80) when compared to the S-TOFHLA and 0.72 (95% CI = 0.65 to 0.78) when compared to the REALM. The SNS predicted numeracy well, with a correlation coefficient of 0.57 (95% CI = 0.47 to 0.65) for the WRAT4, a standardized beta coefficient of 0.30 (p < 0.05) after adjustment for patient demographics, and an AUC of 0.77 (95% CI = 0.70 to 0.82). CONCLUSIONS: The SNS and SLS are reliable, valid tests that can be used to rapidly estimate general health literacy and numeracy skill levels in adult ED patients. Continuing work is needed to establish their ability to predict clinical outcomes. PMID- 22092897 TI - Emergency severity index triage system correlation with emergency department evaluation and management billing codes and total professional charges. AB - OBJECTIVES: All services provided by physicians to patients during an emergency department (ED) visit, including procedures and "cognitive work," are described by common procedural terminology (CPT) codes that are translated by coders into total professional (physician) charges for the visit. These charges do not include the technical (facility) charges. The objectives of this study were to characterize associations between Emergency Severity Index (ESI) acuity level, ED Evaluation and Management (E&M) billing codes 99281-99285 and 99291, and total ED provider charges (sum of total procedure and E&M professional charges). Secondary objectives were to identify factors that might affect these associations and to evaluate the performance of ESI and identified variables to predict E&M code and average total professional charges. METHODS: The authors reviewed 276,824 patient records for calendar year 2007, of which 193,952 adult ED visits from three different ED types (community, university-based academic, and non-university based academic) met inclusion criteria. Correlations between 1) ESI level and E&M billing code per visit by institution and 2) ESI and total professional charges were analyzed using Spearman rank correlation. Linear regression analysis was performed to identify variables that significantly affected these correlations. RESULTS: ESI level and E&M codes were moderately correlated (Spearman r = 0.51). ESI levels corresponded proportionately to higher E&M codes. ESI 1, 2, and 3 most frequently corresponded with E&M level 5 (50, 62, and 45%, respectively), and ESI 4 and 5 most frequently corresponded with E&M level 3 (56 and 67%, respectively). Only age by decade significantly affected the association between ESI level and E&M billing code. The mean total professional charge for all patient encounters was $421 (SD +/- $204) with increasing mean charges per patient by increasing ESI acuity. Race and E&M code significantly affected the relationship between ESI level and total ED professional charges per patient (adjusted r(2) = 0.66). CONCLUSIONS: A moderate, nonlinear correlation exists between ESI acuity levels and ED E&M billing codes. Increasing age affects this correlation. Race and E&M code affect the correlation between ESI level and total professional charges. As such, basic triage data can be used to estimate E&M code and total professional charges. Future studies are needed to validate these findings across other institutional settings. PMID- 22092898 TI - Comparison of experimental chest compression data to a theoretical model for the mechanics of constant peak displacement cardiopulmonary resuscitation. AB - OBJECTIVES: The objective was to validate an existing theoretical model for the mechanics of constant peak displacement cardiopulmonary resuscitation (CPR) using experimental data taken using various back support surfaces at different chest compression (CC) rates. METHODS: A CPR simulator was used to perform constant peak displacement CC on a weighted full-body CPR training manikin supported on surfaces of varying stiffness at different CC rates. The net sternum-to-spine displacement, combined chest and mattress displacement, and axial reaction force were measured during each test. The experimental results were compared to theoretical predictions from the constant peak displacement CPR model. RESULTS: The theoretical model predictions matched the experimental data to within a mean difference of 11.7% at a CC rate of 42 compressions per minute (cpm), 10.0% at a CC rate of 60 cpm, and 10.1% at a CC rate of 96 cpm, for a target maximum sternal displacement of 5.0 cm. The model predictions also show that when the back support stiffness is less than 250 N/cm, the benefit of using a backboard is greater than for stiffer support surfaces. CONCLUSIONS: Good quantitative agreement between the experimental data and the theoretical model suggests that the constant peak displacement CPR model provides reasonable prediction of CC mechanics during CPR over a wide range of CC rates. Conflicts in the literature are also explained by showing that backboards can significantly enhance CPR CC performance when the back support stiffness is less than 250 N/cm, while for surfaces with higher stiffness, the benefit of using a backboard is reduced. PMID- 22092899 TI - The association between emergency medical services field performance assessed by high-fidelity simulation and the cognitive knowledge of practicing paramedics. AB - OBJECTIVES: The objective of this study was to assess the association between the performance of practicing paramedics on a validated cognitive exam and their field performance, assessed on a simulated emergency medical services (EMS) response. METHODS: This was an observational study of paramedics from a single tiered, urban, advanced life support EMS agency. A high-fidelity simulated response to a medical emergency on environmentally realistic sound stages, and the cognitive portion of the national paramedic certification exam, were each assessed as pass or fail. Participants were randomly assigned to one of six simulations designed by the agency's educational staff, medical director, and representatives from the National Registry of EMTs to be equivalently difficult. Simulations were pilot tested to assess content and face validity. Each participant was classified as failing a simulation scenario if his or her score was one standard deviation (SD) below the population mean. RESULTS: There were 107 paramedics who participated in the study. Participants reported a median of 7.7 years of service (interquartile range [IQR] = 4.1 to 12.8 years). Simulation scores were normally distributed. Ninety-two (86.0%) participants received a passing score for the simulation and 77 (72.0%) passed the cognitive exam. There were 70 (65.4%) individuals who passed both the simulation and the cognitive exam, eight (7.5%) who failed both the simulation and the cognitive exam, 22 (20.6%) who passed the simulation but failed the cognitive exam, and seven (6.5%) who failed the simulation but passed the cognitive exam. There was a significant association between passing the cognitive exam and passing the simulation (chi square p-value = 0.02). CONCLUSIONS: This study simultaneously assessed cognitive knowledge and simulated field performance. Utilization of these measurement techniques allowed for the assessment and comparison of field performance and cognitive knowledge. Results demonstrated an association between a practicing paramedic's performance on a cognitive examination and field performance, assessed by a simulated EMS response. PMID- 22092900 TI - The Millennial Generation and "the lecture". AB - This lecture can be viewed in its entirety online by visiting http://vimeo.com/24148123. PMID- 22092901 TI - Society for Academic Emergency Medicine position statement on teacher-learner relationships. PMID- 22092902 TI - Emergency care and the affordable care act: how can we learn from the past to predict the future? PMID- 22092903 TI - PeRLs: changing the way we view lectures. PMID- 22092904 TI - Consensus conference follow-up: inter-rater reliability assessment of the Best Evidence in Emergency Medicine (BEEM) rater scale, a medical literature rating tool for emergency physicians. AB - BACKGROUND: Studies published in general and specialty medical journals have the potential to improve emergency medicine (EM) practice, but there can be delayed awareness of this evidence because emergency physicians (EPs) are unlikely to read most of these journals. Also, not all published studies are intended for or ready for clinical practice application. The authors developed "Best Evidence in Emergency Medicine" (BEEM) to ameliorate these problems by searching for, identifying, appraising, and translating potentially practice-changing studies for EPs. An initial step in the BEEM process is the BEEM rater scale, a novel tool for EPs to collectively evaluate the relative clinical relevance of EM related studies found in more than 120 journals. The BEEM rater process was designed to serve as a clinical relevance filter to identify those studies with the greatest potential to affect EM practice. Therefore, only those studies identified by BEEM raters as having the highest clinical relevance are selected for the subsequent critical appraisal process and, if found methodologically sound, are promoted as the best evidence in EM. OBJECTIVES: The primary objective was to measure inter-rater reliability (IRR) of the BEEM rater scale. Secondary objectives were to determine the minimum number of EP raters needed for the BEEM rater scale to achieve acceptable reliability and to compare performance of the scale against a previously published evidence rating system, the McMaster Online Rating of Evidence (MORE), in an EP population. METHODS: The authors electronically distributed the title, conclusion, and a PubMed link for 23 recently published studies related to EM to a volunteer group of 134 EPs. The volunteers answered two demographic questions and rated the articles using one of two randomly assigned seven-point Likert scales, the BEEM rater scale (n = 68) or the MORE scale (n = 66), over two separate administrations. The IRR of each scale was measured using generalizability theory. RESULTS: The IRR of the BEEM rater scale ranged between 0.90 (95% confidence interval [CI] = 0.86 to 0.93) to 0.92 (95% CI = 0.89 to 0.94) across administrations. Decision studies showed a minimum of 12 raters is required for acceptable reliability of the BEEM rater scale. The IRR of the MORE scale was 0.82 to 0.84. CONCLUSIONS: The BEEM rater scale is a highly reliable, single-question tool for a small number of EPs to collectively rate the relative clinical relevance within the specialty of EM of recently published studies from a variety of medical journals. It compares favorably with the MORE system because it achieves a high IRR despite simply requiring raters to read each article's title and conclusion. PMID- 22092905 TI - Ethics seminar: the hospice patient in the ED: an ethical approach to understanding barriers and improving care. AB - Emergency physicians (EPs) are asked to evaluate and treat a growing population of hospice patients who present to the emergency department (ED) for a number of important reasons. Hospice patients pose unique ethical challenges, and "best practices" for these patients can differ from the life-preserving interventions of usual ED care. Having a solid understanding of professional responsibilities and ethical principles is useful for guiding EP management of these patients. In end-of-life care, EPs need to recognize that there are barriers and complexities to the best management of hospice patients, but they need to commit to strategies that optimize their care. This article describes the case of a hospice patient who presented with sepsis and end-stage cancer to the ED. Patient, system, and physician factors made management decisions in the ED difficult. The goal in the ED should be to determine the best way to address terminally ill patient needs while respecting wishes to limit interventions that will only increase suffering near the end of life. PMID- 22092906 TI - Association of direct helicopter versus ground transport and in-hospital mortality in trauma patients: a propensity score analysis. AB - OBJECTIVES: Helicopter emergency medical services (HEMS) transport of trauma patients has been used for decades. Its use, however, is still a subject of debate, including issues such as high costs, increasing numbers of crashes, and conflicting results regarding effectiveness in reducing mortality. The aim of this study was to examine whether mode of transport (HEMS vs. ground EMS) is independently associated with mortality among trauma patients transported directly from the scene of injury to definitive care. METHODS: All trauma patients transported directly to a Level I or Level II trauma center by either air or ground EMS over a 4-year period were selected from the Oklahoma State Trauma Registry. Multivariable logistic regression was used to develop propensity scores based on variables measured at the scene of injury. The propensity scores represented the predicted probabilities of a patient being transported by HEMS given a specific set of characteristics and were used as a composite confounding variable in subsequent models of the association of mortality and mode of transport. Along with the propensity scores, Injury Severity Scores (ISS), initial Revised Trauma Score (RTS), and distance from the trauma center were included in a Cox proportional hazards model of the association of mode of transport and 24-hour and 2-week mortality. RESULTS: Overall, the hazard ratio (HR) for 2-week mortality in patients transported by HEMS was 33% lower (HR = 0.67, 95% confidence interval [CI] = 0.54 to 0.84) than in patients transported by ground EMS from the scene of injury, after adjustment for the propensity score and other covariates. In subanalyses, the apparent association of a reduction in the hazard of early mortality among patients transported by HEMS was most evident for patients with an RTS based on injury scene vital signs of 3 to 7 (HR = 0.61, 95% CI = 0.46 to 0.82). The point estimate of the HR was similar (HR = 0.65 95% CI = 0.34 to 1.2) in the 75% of cases who had normal vital signs at the scene of injury, although it was no longer statistically significant because crude mortality was very low (1.7%) in this group. Among those with a RTS of 3 or less at the scene, crude mortality was 58%, and mode of transport was not associated with mortality (HR = 1.02, 95% CI = 0.68 to 1.6). CONCLUSIONS: Helicopter EMS transport was associated with a decreased hazard of mortality among certain patients transported from the scene of injury directly to definitive care. Refinements in scene triage and transport guidelines are needed to more effectively select patients that may benefit from HEMS transport from those unlikely to benefit. PMID- 22092907 TI - Commentary: the good, the bad, and the ugly of social media. PMID- 22092908 TI - A case of a young girl with fever and seizure. PMID- 22092910 TI - Assessment of Streptococcus pneumoniae pilus islet-1 prevalence in carried and transmitted isolates from mother-infant pairs on the Thailand-Burma border. AB - Streptococcus pneumoniae pilus islet-1 (PI-1)-encoded pilus enhances in vitro adhesion to the respiratory epithelium and may contribute to pneumococcal nasopharyngeal colonization and transmission. The pilus subunits are regarded as potential protein vaccine candidates. In this study, we sought to determine PI-1 prevalence in carried pneumococcal isolates and explore its relationship with transmissibility or carriage duration. We studied 896 pneumococcal isolates collected during a longitudinal carriage study that included monthly nasopharyngeal swabbing of 234 infants and their mothers between the ages of 1 and 24 months. These were cultured according to the WHO pneumococcal carriage detection protocol. PI-1 PCR and genotyping by multilocus sequence typing were performed on isolates chosen according to specific carriage and transmission definitions. Overall, 35.2% of the isolates were PI-1-positive, but PI-1 presence was restricted to ten of the 34 serotypes studied and was most frequently associated with serotypes 19F and 23F; 47.5% of transmitted and 43.3% of non transmitted isolates were PI-1-positive (OR 1.2; 95% CI 0.8-1.7; p 0.4). The duration of first-ever infant pneumococcal carriage was significantly longer with PI-1-positive organisms, but this difference was not significant at the individual serotype level. In conclusion, PI-1 is commonly found in pneumococcal carriage isolates, but does not appear to be associated with pneumococcal transmissibility or carriage duration. PMID- 22092909 TI - Clinical pathology of Greyhounds and other sighthounds. AB - Owing to the development of Greyhounds as racing sighthounds, these dogs have acquired unique physiologic adaptations that distinguish them from other breeds. Reference intervals for many analytes in retired racing Greyhounds (RRGs) differ from those of other breeds; most of the hematologic differences have also been described in other sighthounds. In this review, we provide a survey of the literature on clinical pathology of Greyhounds and other sighthounds and results of laboratory testing, including analysis of CBCs, biochemical profiles, coagulation tests, and blood gases, in RRGs at The Ohio State University. Major clinicopathologic differences in this breed include higher RBC mass, creatinine concentration, glomerular filtration rate, activities of hepatic enzymes, and concentration of cardiac troponin, as well as lower WBC, neutrophil, and platelet counts, thromboelastographic values, and concentrations of serum haptoglobin, total globulins, and T4. PMID- 22092911 TI - Comparative evaluation of different calcium phosphate-based bone graft granules - an in vitro study with osteoblast-like cells. AB - OBJECTIVE: Granule-shaped calcium phosphate-based bone graft materials are often required for bone regeneration especially in implant dentistry. Two newly developed bone graft materials are Ceracell((r)) , an open-celled highly porous bioceramic from beta-tricalcium phosphate (beta-TCP) under addition of bioglass and Osseolive((r)) , an open porous glass ceramic with the general formula Ca2 KNa(PO4 )2 . The goal of this study was to characterize different modifications of the two bone graft materials in vitro in comparison to already established ceramic bone grafts Cerasorb M((r)) , NanoBone((r)) and BONIT Matrix((r)) . MATERIALS AND METHODS: Adhesion and proliferation of SaOS-2 osteoblast-like cells were evaluated quantitatively by determining DNA content and lactate dehydrogenase (LDH) activity and qualitatively by scanning electron microscopy (SEM). In addition, MTT cell-vitality staining was applied to confirm the attachment of viable cells to the different materials. Osteogenic differentiation was evaluated by measurement of alkaline phosphatase (ALP) activity as well as gene expression analysis of osteogenic markers using reverse transcriptase PCR. RESULTS: DNA content and LDH activity revealed good cell attachment and proliferation for Ceracell and Cerasorb M. When pre-incubated with cell-culture medium, also Osseolive showed good cell attachment and proliferation. Attachment and proliferation of osteoblast-like cells on NanoBone and BONIT Matrix was very low, even after pre-incubation with cell-culture medium. Specific ALP activity on Ceracell((r)) , Osseolive ((r)) and Cerasorb M((r)) increased with time and expression of bone-related genes ALP, osteonectin, osteopontin and bone sialoprotein II was demonstrated. CONCLUSIONS: Ceracell as well as Osseolive granules support proliferation and osteogenic differentiation in vitro and may be promising candidates for in vivo applications. PMID- 22092912 TI - NsrR-dependent method for detecting nitric oxide accumulation in the Escherichia coli cytoplasm and enzymes involved in NO production. AB - A beta-galactosidase assay for detecting the accumulation of NO in the Escherichia coli cytoplasm has been developed based on the sensitive response of the transcription repressor, NsrR, to NO. The hcp promoter is repressed by NsrR in the absence of nitric oxide, but repression is relieved when NO accumulates in the cytoplasm. Most, but not all, of this NO is formed by the interaction of the membrane-associated nitrate reductase, NarG, with nitrite. External NO at physiologically relevant concentrations does not equilibrate across the E. coli membrane with NsrR in the cytoplasm. The periplasmic nitrite reductase, NrfAB, is not required to prevent equilibration of NO across the membrane. External NO supplied at the highest concentration reported to occur in vivo does not damage FNR sufficiently to affect transcription from the hcp or hmp promoters or from a synthetic promoter. We suggest that the capacity of E. coli to reduce NO is sufficient to prevent its accumulation from external sources in the cytoplasm. PMID- 22092913 TI - Oral hygiene, periodontal health and chronic obstructive pulmonary disease exacerbations. AB - AIM: To assess the associations of oral hygiene and periodontal health with chronic obstructive pulmonary disease (COPD) exacerbations. MATERIAL AND METHODS: In total, 392 COPD patients were divided into frequent and infrequent exacerbation (>=2 times and <2 times in last 12 months) groups. Their lung function and periodontal status were examined. Information on oral hygiene behaviours was obtained by interview. RESULTS: In the univariate analysis, fewer remaining teeth, high plaque index (PLI) scores, low tooth brushing times, and low regular supra-gingival scaling were significantly associated with COPD exacerbations (all p-values <0.05). After adjustment for age, gender, body mass index, COPD severity and dyspnoea severity, the associations with fewer remaining teeth (p = 0.02), high PLI scores (p = 0.02) and low tooth brushing times (p = 0.008) remained statistically significant. When stratified by smoking, fewer remaining teeth (OR = 2.05, 95% CI: 1.04-4.02) and low tooth brushing times (OR = 4.90, 95% CI: 1.26-19.1) among past smokers and high PLI scores (OR = 3.43, 95% CI: 1.19-9.94) among never smokers were significantly associated with COPD exacerbations. CONCLUSIONS: Fewer remaining teeth, high PLI scores, and low tooth brushing times are significant correlates of COPD exacerbations, indicating that improving periodontal health and oral hygiene may be a potentially preventive strategy against COPD exacerbations. PMID- 22092914 TI - Emotional responses of mothers of late-preterm and term infants. AB - OBJECTIVE: To compare the emotional responses of mothers of late-preterm infants (34 0/7 to 36 6/7 weeks gestation) with those of mothers of full-term infants. DESIGN: A mixed method comparative study. SETTING: A southeastern tertiary academic medical center postpartum unit. PARTICIPANTS: Sixty mothers: 29 mothers of late-preterm infants and 31 mothers of full-term infants. METHODS: Measures of maternal emotional distress (four standardized measures of anxiety, postpartum depression, posttraumatic stress symptoms, and worry about infant health) and open-ended semistructured maternal interviews were conducted in the hospital following birth and by phone at one month postpartum. RESULTS: Mothers of late preterm infants experienced significantly greater emotional distress immediately following delivery, and their distress levels continued to be higher at one month postpartum on each of the standardized measures. Mothers of late-preterm infants also discussed the altered trajectories in their birth and postpartum experiences and feeling unprepared for these unexpected events as a source of ongoing emotional distress. CONCLUSION: Mothers of late-preterm infants have greater emotional distress than mothers of term infants for at least one month after delivery. Our findings suggest that it may not be a single event that leads to different distress levels in mothers of late-preterm and full-term infants but rather the interaction of multiple alterations in the labor and delivery process and the poorer-than-expected infant health outcomes. In the future, researchers need to examine how and when mothers' emotional responses change over time and how their responses relate to parenting and infant health and development. PMID- 22092915 TI - No detectable beneficial systemic immunomodulatory effects of a specific synbiotic mixture in infants with atopic dermatitis. AB - BACKGROUND: In a murine model of allergic inflammation, Bifidobacterium breve M 16V has been shown to reduce IL-4 and IgE by inducing IL-10 and IFN-gamma. However, it remains unknown whether this strain has the same effect in humans with allergic disease. OBJECTIVE: To determine the effects of Bifidobacterium breve M-16V combined with a prebiotic oligosaccharide mixture (synbiotic) on atopic markers, ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs) and circulating regulatory T cell percentage in infants with atopic dermatitis. METHODS: In a double-blind, placebo-controlled multi-centre trial, 90 infants with atopic dermatitis, age <7 months, were randomized to receive an infant formula with Bifidobacterium breve M-16V and a mixture of short chain galactooligosaccharides and long chain fructooligosaccharides (Immunofortis((r)) ), or the same formula without synbiotics during 12 weeks. At week 0 and 12, plasma levels of IL-5, IgG1, IgG4, CTACK and TARC, ex vivo cytokine responses by PBMCs and percentage of regulatory T cells, were determined. RESULTS: There were no significant differences between the synbiotic and the placebo group in IL-5, IgG1, IgG4, CTACK and TARC levels and ex vivo cytokine production by anti CD3/anti-CD28-stimulated PBMCs. With allergen-specific stimuli, we found a decreased IL-12p40/70 and IL-12p70 production in response to egg allergen (P = 0.04 and P = 0.01, respectively) and decreased IL-12p70 production in response to peanut allergen (P = 0.003) in the synbiotic compared with the placebo group. Circulating regulatory T cell percentage did not significantly differ between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: This synbiotic mixture has no detectable effect on plasma levels of the analysed atopic disease markers, ex vivo cytokine production and circulating regulatory T cell percentage in infants with atopic dermatitis, besides down-regulation of IL-12 production in egg- and peanut-stimulated PBMCs. These results do not support the use of this synbiotic in clinical practice. PMID- 22092916 TI - Labial bone assessment surrounding dental implant using cone-beam computed tomography: an in vitro study. AB - OBJECTIVE: Stable esthetic restoration is required for anterior dental implants, assessed over a long-term follow-up. Cross-sectional images obtained using cone beam computed tomography (CBCT) allow visualization of the bucco-lingual bone surrounding dental implants; however, the thin labial bone surrounding anterior dental implants is unclear. So, the minimum labial bone thickness surrounding dental implants detected using CBCT images was estimated in the present in vitro study. MATERIALS AND METHODS: One dry mandible with five aluminum steps and a titanium rod for simulation of the thin labial bone and dental implant were used. CBCT was performed three times using three exposure volumes, and voxel values of each aluminum step were plotted. Then, the maximum voxel value in each aluminum step as a percentage of that of the 1-mm-thick aluminum step was calculated. RESULTS: The rates for the 0.6-mm-thick aluminum step with a 51- and 102-mm diameter exposure volume were approximately 50% or greater. CONCLUSIONS: When labial bone surrounding the dental implant was approximately 0.6 mm or greater, it was suggested that it might be visually detectable using CBCT images with a 51 and 102-mm-diameter exposure volume. PMID- 22092917 TI - Decreased colonization of fecal Clostridium coccoides/Eubacterium rectale species from ulcerative colitis patients in an in vitro dynamic gut model with mucin environment. AB - The mucus layer in the colon, acting as a barrier to prevent invasion of pathogens, is thinner and discontinuous in patients with ulcerative colitis (UC). A recent developed in vitro dynamic gut model, the M-SHIME, was used to compare long-term colonization of the mucin layer by the microbiota from six healthy volunteers (HV) and six UC patients and thus distinguish the mucin adhered from the luminal microbiota. Although under the same nutritional conditions, short chain fatty acid production by the luminal communities from UC patients showed a tendency toward a lower butyrate production. A more in-depth community analysis of those microbial groups known to produce butyrate revealed that the diversity of the Clostridium coccoides/Eubacterium rectale and Clostridium leptum group, and counts of Faecalibacterium prausnitzii were lower in the luminal fractions of the UC samples. Counts of Roseburia spp. were lower in the mucosal fractions of the UC samples. qPCR analysis for butyryl-CoA:acetate CoA transferase, responsible for butyrate production, displayed a lower abundance in both the luminal and mucosal fractions of the UC samples. The M-SHIME model revealed depletion in butyrate producing microbial communities not restricted to the luminal but also in the mucosal samples from UC patients compared to HV. PMID- 22092918 TI - Cutaneous resonance running time is decreased in psoriatic lesions. AB - BACKGROUND/AIMS: Psoriasis is characterized by lower stratum corneum (SC) hydration and dermal inflammation. Both SC hydration and cutaneous inflammation influence cutaneous resonance running time (CRRT). However, the characteristics of CRRT in psoriatic lesions are largely unknown. In the present study, we assessed whether changes in CRRT occur in psoriatic lesions in Chinese. METHODS: A Reviscometer RVM600 and Corneometer CM 825 were used to measure CRRTs and SC hydration, respectively, in psoriatic lesions (psoriasis vulgaris) on the extensor of forearm in 111 subjects (58 men, 53 women), aged 23-80 years (50.42 +/- 1.23 years). The contralateral uninvolved sites served as control. RESULTS: In comparison with contralateral uninvolved sites, CRRTs in psoriatic lesions were reduced significantly in all directions. There was neither gender nor age difference in the extent of reduction in CRRTs. However, the reduction of CRRTs varied with measurement directions. Positive correlations of SC hydration with CRRTs were found at some directions in uninvolved and involved sites in young men whereas CRRTs in psoriatic lesions were not correlated with SC hydration in either aged or young women. Moreover, CRRT at 0-6 o'clock direction was positively correlated with SC hydration in involved sites of aged men. CONCLUSION: Cutaneous resonance running times are decreased in psoriatic lesions. Reduction of CRRTs varies with measurement directions, but not gender or age. Measurement of CRRTs could be another valuable approach to assess the severity of psoriasis and the efficacy of its treatment. PMID- 22092919 TI - Interview with a quality leader: Carol Wagner on Washington State Hospital Association (WSHA) and their statewide improvement. Interview by Susan V. White. AB - Carol Wagner, RN, MBA is the Vice President for Patient Safety at the Washington State Hospital Association (WSHA). She is recognized nationally as an innovative patient safety leader. She led the development of WSHA's Patient Safety Program and Rural Healthcare Quality Network. Under Carol's leadership, the WSHA received the 2010 John Eisenberg Patient Safety and Quality Award for national innovation given by The Joint Commission and the National Quality Forum. The association also received the 2011 Dick Davidson Award for Allied Association Leadership. These national awards are two of the highest honors an organization can receive for patient safety and quality. Through close working relationships with national and state regulatory bodies and professional organizations, Carol designs programs to improve quality and safety in every hospital in Washington State. Under Carol's leadership, all hospitals in Washington participated in the Institute for Healthcare Improvement's (IHI) 5 Million Lives Campaign. The effort led to implementation of the largest number of rapid response teams in a geographic area. Carol also created the first statewide learning collaborative to reduce hospital-acquired infections. Carol is a registered nurse with an MBA focusing on finance and operations. She worked clinically in a variety of settings, provided leadership as a nursing administrator, and transitioned to lead hospital strategic planning, budgeting, and cost accounting. She studied management and system change at The Wharton School at the University of Pennsylvania. Her quality training was with Dr. W. Edwards Deming and at Intermountain Health Care with Dr. Brent James. Her experience includes work in for-profit and not-for-profit environments and supporting community, tertiary, and academic medical centers. This includes Huntington Hospital in Pasadena, California and a national for-profit hospital system with more than 100 hospitals. PMID- 22092921 TI - Fractional thermoablation using an erbium-doped yttrium aluminum garnet fractionated laser for the treatment of pulsed dye laser-resistant port wine stain birthmarks. PMID- 22092920 TI - Drivers of epsilonproteobacterial community composition in sulfidic caves and springs. AB - Epsilonproteobacteria are widely distributed in marine, freshwater, and terrestrial environments, although most well-studied groups are from hydrothermal vents and the human intestinal tract. The environmental variables that control epsilonproteobacterial communities in sulfidic terrestrial environments, however, are poorly understood. Here, the environmental variables that influence epsilonproteobacterial community composition in geographically separated sulfidic caves and springs were determined by coarse and fine-scale approaches: denaturing gradient gel electrophoresis profiling of 23S rRNA PCR amplicons and clone library sequencing of the 16S-ITS-23S rRNA operon. Sequences retrieved from this study were not closely related to cultured representatives, indicating that existing culture collections do not adequately capture the diversity of terrestrial Epsilonproteobacteria. Comparisons of 16S-ITS-23S rRNA operon sequences from four sites revealed that some distant communities (> 8000 km) share closely related populations of Epsilonproteobacteria, while other sites have nearly clonal and phylogenetically distinct populations. Statistical evaluations of sequence data reveal that multiple environmental variables (e.g. temperature, pH, salinity, dissolved oxygen, and bicarbonate concentrations) influence Epsilonproteobacteria community composition. Locations with clonal populations tended to be from higher temperatures and intermediate dissolved oxygen concentrations. rRNA operon sequences outside of the 16S rRNA gene may be critical to recognizing environmental drivers of epsilonproteobacterial community composition. PMID- 22092922 TI - Effect of acquisition time and chemical fat suppression on meningeal enhancement on MR imaging in dogs. AB - Our purpose was to characterize meningeal gadolinium enhancement on magnetic resonance (MR) imaging in dogs with inflammatory and neoplastic diseases, and to assess interobserver variability and the impact of delayed acquisition and chemical fat saturation on its conspicuity. Transverse T1-weighted FLAIR images were acquired prior to, and immediately following gadolinium injection (T0), and at 5 (T5) and 15-20 min delay (TD), with and without fat suppression, in 155 consecutive dogs imaged for suspected brain disease. The agreement on meningeal enhancement was globally substantial (kappa = 0.61) and the likelihood of obtaining a definite diagnosis was significantly increased with the use of fat suppression (P < or = 0.004). Meningeal enhancement was judged definitively present by consensus in 46 of 155 (30%) dogs. Of these, meningeal enhancement was characterized qualitatively and quantitatively in 30 dogs with a clinical diagnosis (18 inflammatory, 11 neoplastic, 1 infarct), and image sequences were compared. Meningeal enhancement was more often diffuse and leptomeningeal in animals with inflammation versus neoplasia (50% vs. 42%, and 69% vs. 48%, respectively), but significant associations were not found. Meningeal thickness and contrast ratio were higher with neoplasia (P < or = 0.02), but results did not vary significantly between series for either group. Yet, images with fat suppression were most useful 50% of the time for definite diagnosis and/or characterization of meningeal enhancement. While delayed image acquisition following gadolinium injection does not improve characterization of meningeal enhancement in dogs, fat suppression is beneficial qualitatively. PMID- 22092923 TI - Complications associated with implant migration into the maxillary sinus cavity. AB - BACKGROUND: Migration of dental implants into the maxillary sinus is an uncommon, but increasingly reported complication. Implant migration may result from initial lack of primary stability, intrasinusal and nasal pressure changes, autoimmune reaction to the implant or incorrect distribution of occlusal forces. This retrospective study aims at analyzing the factors that may influence implant migration into the maxillary sinus cavity. MATERIAL AND METHODS: Fourteen patients presenting a total 15 implants that migrated into the maxillary sinus were recruited. Diagnosis of this complication was based on imaging techniques, such as cone beam computerized tomography scan and panoramic radiography. Clinical data were recorded in all cases and processed for statistical analysis. RESULTS: ABH was below 6 mm in the majority of cases. However, almost 50% of the patients did not receive any site preparation treatment prior to implant insertion. Five patients (33.3%) were treated by osteotome techniques, but only one of them had bone grafting. Therefore, 73.3% of sites did not receive any biomaterial to increase available bone height. The most common complication associated factors found on this study were related to implant design (cylindrical), implant dimension (diameter), implant restoration/rehabilitation method (partial removable denture), site-specific anatomy (initial residual bone height between 5 and 6.9 mm), demographics (age), and biomaterials. CONCLUSION: Patient selection and proper treatment planning, as well as the application of the appropriate sinus augmentation technique, are critical aspects that should be controlled to minimize the risk of implant migration into the maxillary sinus cavity. PMID- 22092924 TI - Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging. AB - The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging. Structural changes include an increase in the collagen concentration, a change in the elastic fiber system, and an increase in fat infiltration of skeletal muscle. Biochemical changes include a decreased turnover of collagen with potential accumulation of enzymatically mediated collagen cross-links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some of the changes in skeletal muscle ECM with aging may be preventable with resistance or weight training, but it is clear that more human studies are needed on the topic. PMID- 22092925 TI - IL1 gene polymorphisms and unsuccessful dental implants. AB - OBJECTIVES: This study aimed to analyse the association between polymorphisms in the IL1 gene cluster and failure of dental implants in a Portuguese population. MATERIAL AND METHODS: A total of 155 Caucasian Portuguese subjects were divided into two groups: 100 with successful dental implants and 55 with unsuccessful dental implants. DNA was obtained through an oral mucosa scraping. PCR was used to identify the polymorphisms: single nucleotide changes in positions -889 of IL1A gene and +3953 of IL1B gene. RESULTS: The prevalence of the polymorphisms 889IL1A gene and +3953IL1B gene, determined by the positive result of TGP (Genetic Test for Periodontitis; CGC, Genetics, Portugal), in the studied population rehabilitated with dental implants was of 33.50%. Allele 1 of the IL1B gene was the most prevalent (62.20%), followed by allele 1 of the IL1A gene (54.80%) and the least frequent was allele 2 of IL1B gene (37.40%). Success of dental implants was mainly associated with a negative TGP result, whereas no success was found to be related to a positive result. There were no statistically significant differences between the alleles 1 and 2 of the genes IL1A and IL1B and the tobacco and alcohol consumption for the success or no success of the dental implants. CONCLUSIONS: The alleles 1 and 2 of IL1A gene and the alleles 1 and 2 of IL1B gene were statistically associated with the success or no success of the dental implants. Tobacco habit and alcohol consumption showed no statistically significant association with success or no success of the dental implants. PMID- 22092927 TI - Hoping for the best, preparing for the worst: the lived experiences of women undergoing ovarian cancer surgery. AB - In this study, the lived experiences of women undergoing ovarian cancer surgery were explored, aiming to provide a patient perspective on being newly diagnosed and starting treatment for ovarian cancer. The study period ran from the first visit in the outpatient clinic, till 8 weeks later, when the women had either begun chemotherapy or completed their recovery. Ten women participated in two qualitative research interviews each, before and after surgery. By applying a phenomenological-hermeneutic text interpretation methodology, the findings were systematically identified, put into meaning-structures, interpreted and discussed. This process constituted the theme: 'Hoping for the best, preparing for the worst'. Final diagnostics and treatment start were extensive life events, where life itself was threatened, although hope and will were present. The women intuitively prepared themselves for the diagnosis and treatment. However, the ability to prepare was influenced by personal lifestyle, social conditions, coping strategies, and experiences of hope. The ability to prepare could be strengthened by providing adjusted information, psychosocial support and physical optimisation during the perioperative period. By offering targeted family counselling and taking good care of the women's general health and well-being, hope could be sustained and early cancer rehabilitation initiated. PMID- 22092926 TI - Basic pharmacology of topical imiquimod, 5-fluorouracil, and diclofenac for the dermatologic surgeon. AB - BACKGROUND: Ultraviolet radiation (UVR) contributes to the vast majority of nonmelanoma skin cancer (NMSC). As the incidence of NMSC continues to rise, topical therapies will be used with increasing frequency. Topical therapies may benefit high-risk surgical candidates as an alternative treatment modality and may improve overall cosmesis. The most commonly employed topical therapies are imiquimod, 5-fluorouracil (5-FU), and diclofenac. OBJECTIVE: To review the detailed mechanism of action and side-effect profiles of each topical therapy used to treat NMSC and to explore newly discovered actions. Uncommon adverse events are also presented. MATERIALS AND METHODS: An extensive literature search was performed to describe the pharmacologic actions of imiquimod, 5-FU, and diclofenac. CONCLUSION: A keen understanding of the pharmacologic concepts of these topical therapies may aid the dermatologic surgeon in making sound choices before, during, and after surgery. PMID- 22092928 TI - Work-relief ratios and imbalances of load application in sport climbing: another link to overuse-induced injuries? AB - An imbalanced load application of the upper extremity may contribute to overuse induced injuries of the fingers. Thus, the present study evaluated load application symmetry between the right and the left hand and its work-relief ratios (WRR) depending on climbing ability and pre-exhaustion level. Twenty-eight sport climbers (age: 29 +/- 8 years; body mass index: 22 +/- 2 kg/m(2); years of climbing: 10 +/- 6; climbing level: 6+ UIAA to 9 UIAA) were assigned to a group of recreational (<=8-UIAA, n = 14) or a group of ambitious (>=8 UIAA, n = 14) climbers. Blood lactate and perceived exertion level were recorded at the end of the climbing attempt. Load application and WRR were derived from video analysis separately for the left and the right hand. Differences in load-application time between the left (47 +/- 4%) and the right (53 +/- 4%) hand (P < 0.001) were observed. Irrespective of side differences, the overall WRR was 5:1. Increasing climbing level leads to a more symmetric load application (r = -0.42, P < 0.03). Differences of lactate concentration and exertion level were found between the pre- and the non-pre-exhausted group. Depending on climbing ability and exhaustion level, load application for the dominant hand (right) prevails. Further longitudinal studies should focus on imbalanced load application and overuse-induced climbing injuries. PMID- 22092929 TI - Incidental findings from cone beam computed tomography of the maxillofacial region: a descriptive retrospective study. AB - OBJECTIVE: To evaluate the type and prevalence of incidental findings from cone beam computed tomography (CBCT) of the maxillofacial region. Findings are divided into those that require (i) intervention/referral, (ii) monitoring, and (iii) no further evaluation. METHODS: Three hundred consecutive CBCT scans conducted in the University of North Carolina School of Dentistry Oral and Maxillofacial Radiology Clinic from January 1 to August 31, 2008 were retrospectively reviewed. Findings were categorized into airway, soft tissue calcifications, bone, temporomandibular joint (TMJ), endodontic, dental developmental, and pathological findings. RESULTS: A total of 272 scans revealed 881 incidental findings (3.2 findings/scan). The most prevalent was airway findings (35%) followed by soft tissue calcifications (20%), bone (17.5%), TMJ (15.4%), endodontic (11.3%), dental developmental (0.7%), and pathological (0.1%). 16.1% required intervention/referral, 15.6% required monitoring, and the remainder (68.3%) required neither. CONCLUSION: This study underscores the need to thoroughly examine all CBCT volumes for clinically significant findings within and beyond the region of interest. PMID- 22092930 TI - Reference intervals for biochemical analytes in serum and heparinized plasma and serum protein fractions in adult alpacas (Vicugna pacos). AB - BACKGROUND: Species-specific reference intervals for laboratory tests are required for diagnosis and management of disease. Few reports of reference intervals for biochemical analytes and protein fractions are available for alpacas. OBJECTIVES: The aims of this study were to establish reference intervals for biochemical analytes measured in both serum and plasma and in serum protein fractions, and to determine the influence of herd and sex on test results in a population of alpacas. METHODS: Blood was collected from 74 healthy male and female adult alpacas (Vicugna pacos) from 5 herds into tubes with no anticoagulant or with sodium heparin and analyzed within 4 hours. Biochemical analytes and ionized calcium were measured using a Hitachi P modular automated chemistry analyzer and an ABL-800 Flex blood-gas analyzer, respectively, and protein fractions were measured by agarose gel electrophoresis of serum. Nonparametric statistical methods were used to determine reference intervals, results obtained from serum and plasma were compared, and effects of herd and sex were examined. RESULTS: Serum and plasma samples from 71 and 74 alpacas, respectively, were used to establish reference intervals for serum and plasma biochemical analytes. Intervals were similar, although clinically relevant differences between creatine kinase activity and phosphate concentration were found in individual animals. Serum proteins from 60 alpacas were analyzed by electrophoresis. There were significant herd- and sex-associated differences in some biochemical analytes and protein fractions; however, most had minimal impact on reference interval determination, with the exception of herd-associated effects on concentrations of urea nitrogen, ionized calcium, and bile acids and transferrin saturation. CONCLUSIONS: Serum and plasma reference intervals are interchangeable; however, consistency of sample type is imperative when performing serial testing. Use of laboratory- and instrument-specific reference intervals is optimal; however, intervals reported here may be used as a guide for interpreting laboratory results from alpacas, especially when test methods are the same. PMID- 22092931 TI - Periodontitis in non-smoking type 1 diabetic adults: a cross-sectional study. AB - AIM: To compare levels of periodontitis in non-smoking type 1 diabetic patients and controls. MATERIAL AND METHODS: Type 1 diabetic patients, aged 20-55 years, were recruited from outpatient clinics at five hospitals in Glasgow, UK. Control subjects were recruited from physiotherapy clinics, using the buddy system and through an advertisement in a free newspaper. The primary outcome was severe periodontitis defined by clinical attachment level >=6 mm on >=1 tooth. RESULTS: There were 34 well controlled patients (HbA1c <= 7.5%), 169 poorly controlled patients and 112 non-diabetic subjects. Prevalence of severe periodontitis was higher in all type 1 diabetic patients [24.1% (95% CI: 18.4-30.6%)] and poorly controlled patients [27.2% (20.7-34.6%)] than in controls [20.5% (13.5-29.2%)]. The fully adjusted odds ratios (ORs) in never smokers comparing the whole diabetic group, and the poorly controlled group, with the control group were 1.35 [0.66-2.8] (p = 0.41) and 1.58 [0.75-3.33] (p = 0.23), respectively. Mean clinical attachment level was higher in all type 1 diabetic and poorly controlled patients than in controls (both p < 0.001). CONCLUSIONS: These results indicate worse periodontal health in type 1 diabetic patients than in control subjects. TRIAL REGISTRATION: This study was registered with the UKCRN, ID: 9314 and Scottish Diabetes Research Network registration number: 128. PMID- 22092932 TI - Cytological evaluation of the effect of azoxystrobin and alternative oxidase inhibitors in Botrytis cinerea. AB - Azoxystrobin (AZ), a strobilurin-derived fungicide, is known to inhibit mitochondrial respiration in fungi by blocking the electron transport chain in the inner mitochondrial membrane. Germination was strongly inhibited when Botrytis cinerea spore suspension was treated with AZ and the alternative oxidase (AOX) inhibitors, salicylhydroxamic acid (SHAM) and n-propyl gallate. However, chemical death indicators trypan blue and propidium iodide showed that those spores were still alive. When the spore suspension in the AZ and SHAM solution was replaced with distilled water, the germination rate almost recovered, at least during the first 2 days of incubation with AZ and SHAM solution. No morphological alteration was detected in the cells treated with AZ and SHAM, especially in mitochondria, using transmission electron microscopy. Therefore, simultaneous application of AZ and AOX inhibitors has a fungistatic, rather than a fungicidal, action. PMID- 22092933 TI - The relation between coronary artery calcification in asymptomatic subjects and both traditional risk factors and living in the city centre: a DanRisk substudy. AB - OBJECTIVE: To evaluate the association between the risk factor for living in the city centre as a surrogate for air pollution and the presence of coronary artery calcification (CAC) in a population of asymptomatic Danish subjects. DESIGN AND SUBJECTS: A random sample of 1825 men and women of either 50 or 60 years of age were invited to take part in a screening project designed to assess risk factors for cardiovascular disease (CVD). Noncontrast cardiac computed tomography was performed on all subjects, and their Agatston scores were calculated to evaluate the presence of subclinical coronary atherosclerosis. The relationship between CAC and several demographic and clinical parameters was evaluated using multivariate logistic regression. RESULTS: A total of 1225 individuals participated in the study, of whom 250 (20%) were living in the centres of major Danish cities. Gender and age showed the greatest association with the presence of CAC: the odds ratio (OR) for men compared with women was 3.2 [95% confidence interval (CI) 2.5-4.2; P < 0.0001], and the OR for subjects aged 60 versus those aged 50 years was 2.2 (95% CI 1.7-2.8; P < 0.0001). Other variables independently associated with the presence of CAC were diabetes and smoking with ORs of 2.0 (95% CI 1.1-3.5; P = 0.03) and 1.9 (95% CI 1.4-2.5, P < 0.0001), respectively. The adjusted OR for subjects living in city centres compared to those living outside was 1.8 (95% CI 1.3-2.4; P = 0.0003). CONCLUSION: Both conventional risk factors for CVD and living in a city centre are independently associated with the presence of CAC in asymptomatic middle-aged subjects. PMID- 22092934 TI - In vivo reflectance confocal microscopy for varicella prompt diagnosis and treatment in a severely immunosuppressed patient. PMID- 22092936 TI - Alkaline Fe(III) reduction by a novel alkali-tolerant Serratia sp. isolated from surface sediments close to Sellafield nuclear facility, UK. AB - Extensive denitrification resulted in a dramatic increase in pH (from 6.8 to 9.5) in nitrate-impacted, acetate-amended sediment microcosms containing sediment representative of the Sellafield nuclear facility, UK. Denitrification was followed by Fe(III) reduction, indicating the presence of alkali-tolerant, metal reducing bacteria. A close relative (99% 16S rRNA gene sequence homology) to Serratia liquefaciens dominated progressive enrichment cultures containing Fe(III)-citrate as the sole electron acceptor at pH 9 and was isolated aerobically using solid media. The optimum growth conditions for this facultatively anaerobic Serratia species were investigated, and it was capable of metabolizing a wide range of electron acceptors including oxygen, nitrate, FeGel, Fe-NTA and Fe-citrate and electron donors including acetate, lactate, formate, ethanol, glucose, glycerol and yeast extract at an optimum pH of c. 6.5 at 20 degrees C. The alkali tolerance of this strain extends the pH range of highly adaptable Fe(III)-reducing Serratia species from mildly acidic pH values associated with acid mine drainage conditions to alkali conditions representative of subsurface sediments stimulated for extensive denitrification and metal reduction. PMID- 22092935 TI - Presence of functional, autoreactive human milk-specific IgE in infants with cow's milk allergy. AB - BACKGROUND: Occasionally, exclusively breastfed infants with cow's milk allergy (CMA) remain symptomatic despite strict maternal milk avoidance. OBJECTIVE: To determine whether or not persistence of symptoms could be due to sensitization against endogenous human milk proteins with a high degree of similarity to bovine allergens. METHODS: Ten peptides representing known bovine milk IgE-binding epitopes [alpha-lactalbumin (ALA), beta- and kappa-casein] and the corresponding, highly homologous human milk peptides were labelled with sera from 15 breastfed infants with CMA, aged 3 weeks to 12 months, and peptide (epitope)-specific IgE antibodies were assessed. Nine of the 15 breastfed infants became asymptomatic during strict maternal avoidance of milk and other major food allergens; six infants remained symptomatic until weaned. Ten older children, aged 5-15 years, with CMA were also assessed. The functional capacity of specific IgE antibodies was assessed by measuring beta-hexosaminidase release from rat basophilic leukaemia cells passively sensitized and stimulated with human and bovine ALA. RESULTS: A minimum of one human milk peptide was recognized by IgE antibodies from 9 of 15 (60%) milk-allergic infants, and the majority of older children with CMA. Genuine sensitization to human milk peptides in the absence of IgE to bovine milk was occasionally seen. There was a trend towards specific IgE being detected to more human milk peptides in those infants who did not respond to the maternal milk elimination diet than in those who did (P = 0.099). Functional IgE antibody to human ALA was only detected in infants not responding to the maternal diet. CONCLUSIONS AND CLINICAL RELEVANCE: Endogenous human milk epitopes are recognized by specific IgE from the majority of infants and children with CMA. Such autoreactive, human milk-specific IgE antibodies appear to have functional properties in vitro. Their role in provoking allergic symptoms in infants exclusively breastfed by mothers strictly avoiding dietary milk remains unclear. PMID- 22092937 TI - Bio-Oss(r) blocks combined with BMP-2 and VEGF for the regeneration of bony defects and vertical augmentation. AB - OBJECTIVES: The aim of this study was to evaluate the bone formation rate and osseointegration of Bio-Oss((r)) blocks combined with rhBMP-2 and rhVEGF in bony defects and after vertical augmentation. MATERIAL AND METHODS: Bio-Oss((r)) blocks plus rhBMP-2 (BMP), Bio-Oss((r)) blocks plus rhVEGF (VEGF), or Bio Oss((r)) blocks plus rhBMP-2 and rhVEGF (BMPVEGF) were inserted in "critical size defects" (CSD) in the calvariae of adult pigs. Control defects were filled with collagen carrier (Lyostypt((r)) ) plus growth factors and untreated Bio-Oss((r)) blocks (CO). In a second group, Bio-Oss((r)) blocks plus growth factors and untreated Bio-Oss((r)) blocks were used for vertical augmentation of the calvariae. In the first group, the investigation time was 30 days, in the second group it was 30 and 60 days. The bone samples were investigated histomorphometrically, and the newly formed bone (BV/TV) was judged by microradiographic investigation. RESULTS: In the CSD model, the newly formed bone in the region of interest was not significantly different within the groups. In the second setting, the inserted bone blocks exhibited sufficient volume stability with increasing bone formation up to 9.33% +/- 3.92% for BMP, 10.42% +/ 1.81% for BMP/VEGF, 11.01% +/- 4.78% for VEGF, and 10.02% +/- 5.43% for the control group after 60 days. CONCLUSION: In the chosen setting and time frame, de novo bone formation did not increase with the additional use of growth factors. PMID- 22092938 TI - On electronic fetal heart rate monitoring. PMID- 22092939 TI - Relation between bone quality values from ultrasound transmission velocity and implant stability parameters--an ex vivo study. AB - AIM: The objective of this study was to determine the relationship between bone qualities measured by ultrasound transmission velocity (UTV) and primary implant stability parameters measured by radiofrequency analysis (RFA) and push-out test (POT) in an ex-vivo model. MATERIALS AND METHODS: Three blocks of fresh porcine bone samples were obtained from different anatomic regions, correlating to cortical, mixed and cancellous bone. Mechanical bone qualities of these samples were measured using UTV (expressed in m/s) prior to implantation. Three similar implants (4.1 * 11 mm, AstraTech OS) were inserted into each of the procured bone blocks. The evaluation of implant-bone interface stability was evaluated by RFA expressed as implant stability quotient (ISQ), and POT measured in Newton (N). RESULTS: For cortical, mixed and cancellous bone samples UTV values showed a mean of 2049.33, 1728.67 and 1427.67 m/s, respectively. For the implants inserted into cortical, mixed and cancellous bone samples the mean RFA (ISQ) values were 94.33, 81.33 and 63.11, whereas the POT values were >2000, 680 and 290 N, respectively. There was a strong correlation between UTV values and implant stability parameters that was shown descriptively by scatter box plots. CONCLUSION: The bone quality measurements obtained by UTV values significantly correlated to primary implant stability values measured by RFA and push-out test. Moreover, UTV was able to significantly differentiate between the different bone types. This suggested that UTV may be considered as a reasonable instrument to measure bone quality preoperatively and would help clinicians predict primary implant stability before implant insertion. PMID- 22092940 TI - Risk variables in the association between frequency of alcohol consumption and periodontitis. AB - OBJECTIVE: Investigate the association between the frequency of alcohol consumption and periodontitis. Moreover, evaluate the influence of biological, behavioural, and social risk variables in this association. METHODS: Sample was comprised by 542 subjects of both genders, 35-55 years of age, who underwent a complete periodontal examination, and was divided into four groups according to the frequency of alcohol use, based on alcohol use disorders identification test (AUDIT) and Cut-down, Annoyed, Guilty, Eye-opener (CAGE) instruments: (1) no or occasional alcohol use (NA), (2) moderate alcohol use (MA), (3) intense alcohol use (IA) and (4) alcohol dependence (DA). Associations between the occurrence of periodontitis and potential risk variables were analysed by univariate and multivariate logistic regression stratified by smoking status when appropriate. RESULTS: The prevalence of periodontitis in NA, MA, IA and DA groups were 17.2%, 24.0%, 29.6% and 53%, respectively. Alcohol odds ratio (OR) estimates significantly increased with an increase in consumption frequency (DA>IA>MA>NA) and were approximately two times higher in smokers (OR = 3.43 to 7.91) compared to non-smokers (OR = 1.22 to 3.02). CONCLUSION: Occurrence of periodontitis among alcohol users were high and the frequency of alcohol consumption increased the odds of periodontitis incrementally mainly in smokers. PMID- 22092941 TI - Maintaining tissue orientation during mohs micrographic surgery: scalpel versus marker. AB - BACKGROUND: Critical to the accuracy of Mohs surgery is the ability to maintain proper orientation of excised tissue with respect to the surrounding skin. Several techniques have been described for maintaining this orientation, although no prior investigations directly compare these techniques. OBJECTIVE: To compare the incidence of tissue orientation loss resulting from inability to identify skin score marks with that occurring from failure to identify marks made using a gentian violet marker during Mohs micrographic surgery (MMS). We also sought to determine the incidence of scars resulting from skin scoring. MATERIALS AND METHODS: Patients undergoing MMS were prospectively randomized to have their tissue margins oriented using light scoring using a scalpel versus marking them using a gentian violet marker. Incidence of scoring scars and tissue orientation loss were the primary outcome measures. RESULTS: Data were analyzed for 101 tumors. There were no instances of tissue orientation loss in the scalpel or marker arms, nor were there any visible score mark scars at follow-up. CONCLUSION: Incidence of excessive scars resulting from lightly scored tissue or loss of tissue orientation caused by lost gentian violet markings appears to be low. Both methods worked well within the confines of this study. PMID- 22092942 TI - Commentary on treatment of acne scars in Asian Patients using a 2,790-nm fractional yttrium scandium gallium garnet laser. PMID- 22092943 TI - Giant schwannoma of the little finger. PMID- 22092944 TI - Letter: "mushroom-cloud sign" of melanoma. PMID- 22092945 TI - Letter: successful treatment of multiple miliary osteomas of the face using an erbium-doped yttrium aluminum garnet laser. PMID- 22092946 TI - Letter: treatment of ingrown toenail with a novel instrument. PMID- 22092947 TI - Prevalence and diversity of allergic rhinitis in regions of the world beyond Europe and North America. AB - BACKGROUND: There is comparatively little information in the public domain on the diversity in prevalence and triggers/factors associated with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western-Europe and North America. OBJECTIVE: To review the prevalence and the sensitizing agents/triggers and factors associated with AR/C in several countries in Africa, the Asia-Pacific region, Australia, Eastern Europe, Latin America, Middle East and Turkey. METHODS: Articles published in English in peer-reviewed journals were assessed and selected for further review, following an extensive literature search using the Medline database. RESULTS: This review demonstrated that prevalence of AR and AR/C in these regions has predominantly been investigated in children; with studies indicating wide inter- and intra-regional variations ranging from 2.9% AR and 3.8% AR/C in 10-18-years-old children from one region in Turkey to 54.1% AR and 39.2% AR/C in 13-14-years-old children in one region in Nigeria. Moreover, the prevalence of AR and AR/C has increased markedly over the last decade particularly in some of the more affluent African countries, China Taiwan and several Middle East countries, likely as a consequence of improved living standards leading to increased exposure to multiple traditional and non traditional sensitizing agents and risk factors similar to those noted in western Europe and North America. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that the greater diversity in prevalence of AR or AR/C in populations in these regions is in contrast to the lower diversity of AR or AR/C in the 'western populations (USA and Europe), which tend to be more uniform. This review provides a comprehensive database of the important allergens and triggers which are likely to influence the prevalence of allergic rhinitis in these diverse regions, where the prevalence of allergic rhinitis is increasing and its adverse impact on the quality of life of affected individuals is increasingly recognised. PMID- 22092948 TI - Just scratching the surface: an expanding view of the Cpx envelope stress response. AB - To detect and effectively respond to damage to the cell envelope, Gram-negative bacteria possess multiple envelope stress responses. Among these, the CpxAR two component system has been shown to sense the presence of misfolded periplasmic proteins and increase the production of envelope-localized protein folding and degrading factors in response. However, recent studies have revealed that additional parameters, such as adhesion and central metabolism, can also be sensed by the Cpx signalling system. The discovery that the Cpx regulon contains dozens to hundreds of genes indicates that the cellular functions of the Cpx response are also likely much broader than previously realized. These newly recognized functions include other aspects of envelope maintenance, communication with other regulatory pathways, and pathogenesis. A new model is emerging in which the Cpx response integrates diverse signals and promotes cell survival by protecting the envelope in multiple ways. PMID- 22092949 TI - Twelve-month fall outcomes among delirium subtypes. AB - PURPOSE: The purpose of this study was to examine falls as an outcome measure at 12 months for two-group comparison (delirium cases and noncases) and five-group comparison (noncases, hypoactive, hyperactive, mixed delirium cases, and subsyndromal delirium cases). DESIGN: Three hundred and twenty patients enrolled in the Delirium in Rural Long-Term Care Facilities Study, which examined subjects for delirium during a 28-day surveillance period, were followed longitudinally for fall events for 12 months. Fall events were recorded and data analyzed using date of "first fall" as the referent for statistical analysis. METHODS: Fall reports were completed for all subjects for 12 months following delirium surveillance. Fall records were reviewed and the number of days until the first fall event was calculated. Data were censored for deaths that occurred during the 12-month period. FINDINGS: Five group analysis of variance (noncases, hyperactive delirium, hypoactive delirium, mixed delirium, and subsyndromal delirium) showed significant differences in Functional Independence Measure scores (p = .001) and number of medications (p = .001). The percentage of patients who fell was higher in all delirium subtypes than in noncases at 12 months and was statistically significant for subsyndromal subjects. Two patients, one each from the subsyndromal and mixed delirium subtypes, died from injuries sustained during falls. CONCLUSIONS: Delirium appears to increase the risk for falls. CLINICAL RELEVANCE: Increased surveillance and fall prevention strategies are needed for patients who experience transient cognitive changes such as delirium and subsyndromal delirium, even after delirium resolution. PMID- 22092950 TI - Skin surface hydration decreases rapidly during long distance flights. AB - INTRODUCTION: Dehydration of the stratum corneum leads to sensations and symptoms of 'dry skin' such as skin tightness and itchiness. As these complaints are frequently experienced by airline travellers, the aim of this study was to investigate the changes in skin surface hydration during long distance flights. METHODS: The study was performed on four healthy Caucasian, and on four Japanese women aged 29-39 years, travelling on long distance flights. They had stopped using skin care products at least 12 h before, and did not apply them during the flights. The air temperature and relative humidity inside the cabin, as well as skin capacitance of the face and forearm of participants, were registered at several time points before and during the flights. RESULTS: Relative humidity of the aircraft cabin dropped to levels below 10% within 2 h after take-off and stayed at this value throughout the flight. Skin capacitance decreased rapidly on both the face and forearms with most pronounced changes on the cheeks where it decreased by up to 37%. CONCLUSION: Our results demonstrate that during long distance flights, the aircraft cabin environment leads to a rapid decrease in stratum corneum hydration, an alteration, which probably accounts for the discomfort experienced by long distance aircraft travellers. PMID- 22092952 TI - Midface rejuvenation: an innovative technique to restore cheek volume. PMID- 22092951 TI - Microbial community analysis in the termite gut and fungus comb of Odontotermes formosanus: the implication of Bacillus as mutualists. AB - The microbial communities harbored in the gut and fungus comb of the fungus growing termite Odontotermes formosanus were analyzed by both culture-dependent and culture-independent methods to better understand the community structure of their microflora. The microorganisms detected by denaturing gradient gel electrophoresis (DGGE), clonal selection, and culture-dependent methods were hypothesized to contribute to cellulose-hemicellulose hydrolysis, gut fermentation, nutrient production, the breakdown of the fungus comb and the initiation of the growth of the symbiotic fungus Termitomyces. The predominant bacterial cultivars isolated by the cultural approach belonged to the genus Bacillus (Phylum Firmicutes). Apart from their function in lignocellulosic degradation, the Bacillus isolates suppressed the growth of the microfungus Trichoderma harzianum (genus Hypocrea), which grew voraciously on the fungus comb in the absence of termites but grew in harmony with the symbiotic fungus Termitomyces. The in vitro studies suggested that the Bacillus sp. may function as mutualists in the termite-gut-fungus-comb microbial ecosystem. PMID- 22092953 TI - Imaging diagnosis--Ventriculo-peritoneal shunt associated infection in a dog. AB - Ventriculo-peritoneal shunting is a surgical treatment for hydrocephalus. Complications of this procedure are not well described in dogs. The most common complication in humans is infection, which can be fatal if not diagnosed and treated quickly. We describe the magnetic resonance (MR) imaging characteristics of a shunt-associated cerebral infection in a dog. The MR features of the infection included hyperintensity of the lining of the ventricular system visible on a T2-weighted FLAIR sequence and marked linear contrast enhancement of the ependymal layer on T1-weighted sequences, similar to that described in people. PMID- 22092954 TI - Bacterivory by phototrophic picoplankton and nanoplankton in Arctic waters. AB - Mixotrophy, the combination of phototrophy and heterotrophy within the same individual, is widespread in oceanic systems. Yet, neither the presence nor ecological impact of mixotrophs has been identified in an Arctic marine environment. We quantified nano- and picoplankton during early autumn in the Beaufort Sea and Canada Basin and determined relative rates of bacterivory by heterotrophs and mixotrophs. Results confirmed previous reports of low microbial biomass for Arctic communities in autumn. The impact of bacterivory was relatively low, ranging from 0.6 * 10(3) to 42.8 * 10(3) bacteria mL(-1) day(-1) , but it was often dominated by pico- or nanomixotrophs. From 1% to 7% of the photosynthetic picoeukaryotes were bacterivorous, while mixotrophic nanoplankton abundance comprised 1-22% of the heterotrophic and 2-32% of the phototrophic nanoplankton abundance, respectively. The estimated daily grazing impact was usually < 5% of the bacterial standing stock, but impacts as high as 25% occurred. Analysis of denaturing gradient gel electrophoresis (DGGE) band patterns indicated that communities from different depths at the same site were appreciably different and that there was a shift in community diversity at the midpoint of the cruise. Sequence information from DGGE bands reflected microbes related to those from other Arctic studies, particularly from the Beaufort Sea. PMID- 22092955 TI - The effect of using a relaxation tape on pulse, respiration, blood pressure and anxiety levels of surgical patients. AB - AIM: This study aims to investigate the effect of a relaxation tape on levels of anxiety in surgical patients. BACKGROUND: Surgery is a stressful event for patients. Because of uncertainty regarding surgery and anaesthesia, patients often experience heightened anxiety and fear. DESIGN: A one-group pretest-post test quasi-experimental design. METHODS: Samples were taken from surgical patients in a medical centre in northern Taiwan. The patients were given relaxation tapes the day before their scheduled surgery. Tests were conducted before and after patients listened to the tapes. STAI and respiration, pulse and blood pressure were used to collect data measurements on the anxiety level of these patients. RESULTS: The average age of 80 patients was 43.14 (SD 17.27) years. After the patients listened to the relaxation tape, their respiration rate dropped from 18.4 (SD 6.9) -17.8 (SD 7.4), pulse rate dropped from 81.9 (SD 33.5) - (SD 33.7), systolic blood pressure decreased from 125.4 (SD 16) mmHg - 121.5 (SD 13.4) mmHg and STAI score dropped from 50.9 (SD 11.1) - 41.1 (SD 9.8). They all showed a significant level of difference (p < 0.05). A one-time listen to the tape during the entire hospital stay was the experience of the majority (66.3%) and indicated that the STAI score can be further reduced by increasing the number of tape listening sessions (F = 14.1, p < 0.001). CONCLUSION: The results show that a relaxation tape can significantly reduce the level of anxiety and vital signs related to anxiety in surgical patients. Relevance to clinical practice. The results of this study can provide an empirical basis for nursing treatments. We recommend that relaxation tapes be included in standard of care to alleviate anxiety in surgical patients. PMID- 22092956 TI - Bacterial communities associated with a mineral weathering profile at a sulphidic mine tailings dump in arid Western Australia. AB - We investigated bacterial community assemblages and functions down a hill slope contaminated by tailings from a volcanogenic massive sulphide mine in arid Western Australia. Weathering of waste rock, high in S and Fe, had resulted in a varying elemental dispersal down a face of the tailings hill. Bacterial community assemblage, characterised by PCR-DGGE fingerprinting, was significantly associated with electrical conductivity (E.C.) (rho = 0.664; P < 0.01). Analysis of mobile salts showed that E.C. values were driven by ionic S, Zn, Cl and Al. The bacterial community assemblage was directly characterised across an E.C. gradient using an oligonucleotide microarray (PhyloChip). The dominant taxa at the site were Proteobacteria, Actinobacteria and Firmicutes; however, 37 phyla were detected. The most responsive taxa to variation in E.C. was Acidobacteria (negative correlation). Patterns of heterotrophic processes (BioLog analysis) were also best explained by variation in E.C. (rho = 0.53; P < 0.01), showing a link between primary mineral weathering by lithotrophic bacteria and abiotic processes, and secondary biogeochemical processes by heterotrophic taxa. These data significantly broaden our knowledge of the bacteria present in metallomorphic ecosystems, establish that mobile phase elements are key drivers of community structure, and that primary biogeochemical cycling is directly influencing other geochemical interactions in the samples. PMID- 22092957 TI - The effect of loading in regenerated bone in dehiscence defects following a combined approach of bone grafting and GBR. AB - OBJECTIVES: To evaluate by histology the effect of loading on the regenerated bone at dehiscence type defects around implants when treated with a combined approach of bone grafting and guided bone regeneration (GBR). MATERIALS AND METHODS: In twelve Gottingen mini-pigs, the lower premolars and first molars were extracted and the alveolar process was reduced in width. After 3 months, two Straumann SLActive (Straumann AG, Basel, Switzerland) implants were placed in each hemi-mandible. Twelve implants were placed into the reduced alveolar ridge (group P) with no further defect or treatment on the site, while on 36 implants, buccal dehiscence defects were created and treated as follows: Group T1: synthetic bone substitute (Straumann Bone Ceramic, SBC, Straumann AG). Group T2: SBC with a polyethylene glycol membrane (Straumann MembraGel, Straumann AG); Group N: the dehiscence remained untreated. Three months following implantation, long, custom-made, healing abutments were placed in one hemi-mandible only to ensure functional loading. After 2 months, histological analysis was performed. RESULTS: A trend for lower residual defect height and higher bone-to-implant contact was observed in the loaded sites compared with non-loaded sites in groups P, T1 and N. In group T2, the opposite effect was observed. In terms of bone formation, sites treated with SBC grafting and GBR (group T2) exhibited the largest surface area of regenerated bone followed by T1 and N. Significant resorption of the graft particles was noted in group T2 and the graft surface area occupied by SBC was significantly higher in group T1 compared with group T2 (P < 0.05). CONCLUSIONS: Loading may have a positive effect on bone-to-implant contact in implants inserted in pristine bone or inserted in dehiscence sites and treated by grafting/no grafting. PMID- 22092958 TI - Comparative investigation of the effects of different materials used with a titanium barrier on new bone formation. AB - OBJECTIVES: In this study, we aimed to study the effects on new bone formation of autogenous blood, deproteinized bovine bone graft (DBBG), and biphasic calcium phosphate (BCP) bioceramic graft materials placed under titanium barriers. MATERIAL AND METHODS: Twenty-four adult male New Zealand white rabbits were used in this study. Two titanium barriers were fixed on each rabbit's calvarium. The study included four groups, one of which was a control group. The experiment groups, autogenous blood, DBBG (Bio-Oss((r)) ; Geistlich Biomaterials, Wolhusen, Switzerland) and BCP (4Bone(TM) ; Biomatlante, Vigneux de Bretagne, France) were placed under titanium barriers; in the control group, no materials were used. Half of the animals were sacrificed after 1 month, and the rest were sacrificed after 3 months. After this, micro-computerized tomography images were taken, and a histomorphometric evaluation was carried out. RESULTS: The amounts of new bone formation were found to be higher at the third month than at the first month. The differences between the groups were examined with both a micro-computerized tomography and histomorphometric analysis, and no statistical significance was noted in the first month. In contrast, the increase in the amount of new bone formation at the third month was found to be statistically significant only between the DBBG and control groups (P < 0.05). CONCLUSION: Autogenous blood with titanium barriers in guided bone regeneration seems to be as successful as DBBG and BCP bioceramic graft material. PMID- 22092959 TI - Detecting and measuring small numbers of viable Coxiella burnetii. AB - Coxiella burnetii is an acidophilic, intracellular bacterium that causes the human disease Q fever. In some studies, it is important to distinguish between viable and nonviable C. burnetii. We compared four methods for detecting and measuring viable C. burnetii in biological samples as follows: growth in two different cell culture lines, infection of severe combined immunodeficient (SCID) mice (leading to death) and infection of SCID mice with detection of C. burnetii in their spleen (after euthanasia at day 50 postinfection). Two isolates of C. burnetii were used ('Henzerling' and 'Arandale'). Our in-house qPCR assay for C. burnetii DNA was used as a control. SCID mouse inoculation was more sensitive than cell culture. The assay that detected C. burnetii in SCID mouse spleens was slightly more sensitive than SCID mice deaths alone. Approximately one viable C. burnetii cell could be detected by this method, making it suitable for determining the viability of C. burnetii in a sample. PMID- 22092960 TI - Physiological and performance adaptations to an in-season soccer camp in the heat: associations with heart rate and heart rate variability. AB - The aim of the present study was to examine the associations between adaptive responses to an in-season soccer training camp in the heat and changes in submaximal exercising heart rate (HRex, 5-min run at 9 km/h), postexercise HR recovery (HRR) and HR variability (HRV). Fifteen well-trained but non-heat acclimatized male adult players performed a training week in Qatar (34.6 +/- 1.9 degrees C wet bulb globe temperature). HRex, HRR, HRV (i.e. the standard deviation of instantaneous beat-to-beat R-R interval variability measured from Poincare plots SD1, a vagal-related index), creatine kinase (CK) activity, plasma volume (PV) changes, and post-5-min run rate of perceived exertion (RPE) were collected at six occasions in temperate environmental conditions (22 degrees C). Players also performed the yo-yo intermittent recovery test level 1 (Yo-Yo IR1) in the same environmental conditions (22 degrees C), both at the beginning and at the end of the training week. Throughout the intervention, HRex and HRV showed decreasing (P < 0.001) and increasing (P < 0.001) trends, respectively, while HRR remained unaffected (P = 0.84). Changes in HRex [-0.52, 90% confidence limits ( 0.64; -0.38), P < 0.001] and SD1 [0.35 (0.19; 0.49), P < 0.001] were correlated with those in PV. There was no change in RPE (P = 0.92), while CK varied according to training contents (P < 0.001), without association with HR-derived measures. Yo-Yo IR1 performance increased by 7 +/- 9% (P = 0.009), which was correlated with changes in HRex [-0.64 (-0.84; -0.28), P = 0.01]. In conclusion, we found that an in-season soccer training camp in the heat can significantly improve PV and soccer-specific physical performance; both of which are associated with changes in HRex during a 5-min submaximal run. PMID- 22092961 TI - Immunohistochemical analysis of matrix metalloproteinase-9, vascular endothelial growth factor, bone sialoprotein and i-nitric oxide synthase in calvaria vs. iliac crest bone grafts. AB - OBJECTIVES: The aim of this study was to investigate, in parallel to clinical and histological modifications, the expression of specific proteins involved in different extraoral autologous bone grafts integration in humans. MATERIAL AND METHODS: Patients needing oral rehabilitation of posterior maxilla, with inadequate bone volume for implant placement, received bone grafts from calvaria (Group 1) and iliac crest (Group 2), respectively. From five patients from each group, with a total of 10 subjects, bone biopsy specimens were collected at two different experimental time points: at bone blocks withdrawal for grafting (T0), from donor sites, and after 4 months, from reconstructed sites. Samples were processed for light microscope and immunohistochemical analyses to evaluate MMP9, VEGF, BSP, iNOS expression. RESULTS: Morphological analysis of T0 calvaria evidenced areas of extracellular matrix, uniformly stained and organized in concentric mineralized lamellae edging few vascular canals, while T0 iliac crest showed greater cellularity compared to calvaria, with rare mineralized areas, surrounding wide bone marrow lacunae. In T1, Group 1 samples showed large areas of extracellular matrix, uniformly stained, at the same time as Group 2 samples disclosed few areas of mineralized tissue. Although no significant differences were found in proteins expression among calvaria and iliac crest T0 samples, MMP9, VEGF and BSP expression at T1 were discovered higher in Group 1 samples than in Group 2 ones, while iNOS expression increased in Group 2 samples compared to the others. In any group, molecules expression increased passing from T0 to T1. CONCLUSION: These findings suggested that, even though clinically both extraoral sources of autologous bone could be considered suitable for grafting in case of large oral rehabilitation, some differences might be detected microscopically and biologically. Calvaria bone graft seemed to enhance not only the quantity of bone tissue at the defect site, but also its quality, better than iliac crest bone do. Then, while both grafts appeared to promote a suitable neoangiogenesis, as showed by morphological analysis and by MMP9 and VEGF expression, in terms of new bone formation and lack of occurrence of inflammatory events, calvaria could be considered a more suitable donor site for bone grafts. PMID- 22092962 TI - Double-blind, randomized, controlled clinical trial to compare safety and efficacy of a metallic cannula with that of a standard needle for soft tissue augmentation of the nasolabial folds. AB - BACKGROUND: Injection-related side effects and complications are likely to occur during or after filler injections; they are mainly caused by the injection technique. OBJECTIVE: To assess safety and efficacy of a metallic cannula to inject hyaluronic acid (HA) filler in the nasolabial folds and to compare the safety of this cannula with that of a standard needle. METHODS: This was a prospective, randomized, phase II, double-blinded study that included 25 participants with Grade 2 to 3 for bilateral nasolabial folds according to the Modified Fitzpatrick Wrinkle Scale (MFWS). The side of the injection was randomized (cannula or needle), and 0.5 mL of HA was injected into each nasolabial fold. RESULTS: At day 3, mean MFWS score fell from 2.40 +/- 0.40 to 1.46 +/- 0.52 (p < .001) on the cannula-injected side and from 2.40 +/- 0.40 to 1.48 +/- 0.60 (p < .001) on the regular needle-injected side. Participants reported fewer side effects on the side injected with the new tool on the day of the injections: pain (p = .03), edema (p < .001), redness (p = .01) and hematoma (p < .001) than on the needle side. CONCLUSION: The new cannula is a safe and useful tool to inject HA fillers in the nasolabial folds, producing less pain, edema, hematoma, and redness than regular needles. PMID- 22092963 TI - Asymptomatic Achilles, patellar, and quadriceps tendinopathy: a longitudinal clinical and ultrasonographic study in elite fencers. AB - Lower limb tendon changes detected at imaging are common among asymptomatic athletes. We aimed to prospectively assess the clinical status, tendon structure, and vascularity of lower limb tendons of elite fencers, and predict the risk of developing symptoms over time. Clinical examination, changes at ultrasonography (US), and Power Doppler (PD) flow of both the Achilles, patellar, and quadriceps tendon were assessed in 37 elite fencers in January 2007 and 3 years after. Two hundred and twenty-two tendons were examined. At the last appointment, patellar tendons diagnosed as abnormal at baseline were more likely to develop symptoms than those normal at baseline (P < 0.05, Fisher's exact test), while US and PD abnormalities on Achilles and quadriceps tendons were no predictive for development of symptoms over years. A very low percentage of tendons diagnosed as normal at baseline (1.45%) showed US abnormalities at 3-year follow-up. In asymptomatic elite fencers, structural changes are relatively common at US and PD assessment of Achilles, quadriceps, and patellar tendons. It seems unlikely that additional PD investigations provide further information or change prognosis in patients with US diagnosis of tendinopathy. PMID- 22092964 TI - Evaluation of Staphylococcus aureus virulence factors using a silkworm model. AB - Previous studies have indicated that the silkworm model is useful for identifying virulence genes of Staphylococcus aureus, a human pathogenic bacterium. Here we examined the scope of S. aureus virulence factors that can be evaluated using the silkworm model. Gene-disrupted mutants of the agr locus, arlS gene and saeS gene, which regulate the expression of cell surface adhesins and hemolysins, exhibited attenuated virulence in silkworms. Mutants of the hla gene encoding alpha hemolysin, the hlb gene encoding beta-hemolysin, and the psmalpha and psmbeta operons encoding cytolysins, however, showed virulence in silkworms indistinguishable from that of the parent strain. Thus, these S. aureus cytolysins are not required for virulence in silkworms. In contrast, the gene disrupted mutants of clfB, fnbB and sdrC, which encode cell-wall-anchored proteins, attenuated S. aureus virulence in silkworms. In addition, the mutant of the srtA gene encoding sortase A, which anchors cell-wall proteins, showed attenuated virulence in silkworms. These findings suggest that the silkworm model can be used to evaluate S. aureus cell-wall proteins and regulatory proteins as virulence factors. PMID- 22092965 TI - What is your diagnosis? Serum biochemical data from Sprague-Dawley rats in a toxicology study. PMID- 22092966 TI - Effect of dust storm events on daily emergency admissions for respiratory diseases. AB - BACKGROUND AND OBJECTIVE: The harmful effect of dust storm on lung health is controversial. This study aimed to assess any associations between dust storms and emergency hospital admissions due to respiratory disease in Hong Kong. METHODS: Data on daily emergency admissions for respiratory diseases to major hospitals in Hong Kong, and indices of air pollutants and meteorological variables from January 1998 to December 2002 were obtained from several government departments. We identified five dust storm days during the study period. Independent t-tests were used to compare the mean daily number of admissions on dust storm and non-dust storm days. Case-crossover analysis using the Poisson regression was used to examine the effects of PM(10) to emergency hospital admissions due to respiratory diseases. RESULTS: Significant increases in emergency hospital admission due to COPD were found 2 days after dust storm episode. The relative risk of PM(10) for lag 2 days was 1.05 (95% CI: 1.01-1.09) per 10 ug/m(3) . CONCLUSIONS: Dust storms have an adverse effect on emergency hospital admission for COPD in Hong Kong. This also suggests the adverse effect of coarse particles on lung health. PMID- 22092967 TI - Evaluation of therapeutic sublingual vaccines in a murine model of chronic house dust mite allergic airway inflammation. AB - BACKGROUND: Second generation therapeutic vaccines based upon recombinant allergens or natural extracts, potentially formulated in vector systems or adjuvants, are being developed. To this aim, preclinical studies in relevant animal models are needed to select proper allergens, formulations and administration schemes. OBJECTIVE: To develop a chronic house dust mite (HDM) allergy model to evaluate sublingual therapeutic vaccine candidates. METHODS: The BABL/c mice that were used were sensitized with Dermatophagoides pteronyssinus (Dpte) and Dermatophagoides farinae (Dfar) mite extracts by intraperitoneal injections followed by aerosol exposures. Animals subsequently underwent sublingual immunotherapy (SLIT) with either Dpte, Dfar or Dpte/Dfar extracts, twice a week for 8 weeks. SLIT efficacy was assessed by whole body plethysmography, lung histology and broncho-alveolar lavages cell counts. Specific T cell and antibody responses to major and minor HDM allergens were monitored in tissues and serum/saliva, respectively. RESULTS: Mice sensitized to Dpte and Dfar allergens exhibited strong airway hyperresponsiveness (AHR) and lung inflammatory infiltrates including eosinophils. Sensitized animals mounted Th2-biased cellular and humoral responses specific for group 1 and 2 major allergens, as well as group 5, 7 and 10 minor allergens. This phenotype was sustained for at least 2 months, allowing the evaluation of immunotherapeutic protocols with HDM extracts-based vaccines. In this model, SLIT decreased AHR and Th2 responses and induced HDM-specific IgAs in saliva. The Dpte/Dfar mix proved the most efficacious when compared to Dpte or Dfar extracts alone. CONCLUSIONS AND CLINICAL RELEVANCE: The efficacy of a sublingual vaccine based on a Dpte/Dfar allergen extract mix was demonstrated in a well standardized murine model of chronic allergic airway inflammation based on clinically relevant mite allergens. The latter will be used as a benchmark for evaluation of future vaccines, including recombinant allergens. This HDM allergic airway inflammation animal model is a useful tool to design and select candidate vaccines to be tested in humans. PMID- 22092968 TI - Serum high-density lipoprotein cholesterol level associated with the extent of periodontal inflammation in type 1 diabetic subjects. AB - AIM: High-density lipoprotein (HDL) cholesterol is known for its anti inflammatory and antioxidant activities in protection against cardiovascular diseases. We investigated whether a protective association also exists between serum HDL and periodontal inflammation in type 1 diabetic subjects (T1DM). METHODS: Plaque and periodontal inflammation (bleeding and PD >= 4 mm) were examined in 80 subjects with T1DM. The serum levels of glycosylated haemoglobin (HbA1c, %) and HDL (mmol/l) were determined. Adjusted associations between inflammation and serum HDL were analysed using linear regression analysis. To study the linearity of the association, the subjects were categorized into HDL tertiles (I-III). RESULTS: A statistically significant negative association was observed between serum HDL level and the extent of bleeding and PD >= 4 mm. Subjects in HDL tertiles II and III (high HDL) presented significantly fewer inflamed sites when compared with the subjects in tertile I (low HDL), whereas no significant difference in the number of inflamed sites was observed between tertiles II and III. CONCLUSIONS: Based on the finding of a negative association between serum HDL and periodontal inflammation, HDL may be considered a marker of susceptibility to periodontal inflammation. A longitudinal study is needed to verify possible causal relationship between serum HDL and inflammation. PMID- 22092969 TI - Changes of oxygen content in facial skin before and after cigarette smoking. AB - BACKGROUND/PURPOSE: Cigarette smoking not only causes systemic health problems, but may also be an underlying cause of premature skin aging. Cigarette smokers frequently have morphological changes in facial skin that may be attributed to reduced oxygen in this region. The purpose of this study was to measure the oxygen content in facial skin before and after smoking. METHODS: Twenty-five volunteers participated in this study. Changes in oxygen content of the facial skin were measured before and after 30 min of cigarette smoking. Skin temperature and oxygen content were evaluated in the periorbital and periolar regions. RESULTS: There was a significant increase in temperature after smoking. The oxy hemoglobin and partial pressure of oxygen decreased in both the periocular and perioral areas after smoking. There were no changes in deoxy hemoglobin and partial pressure of carbon dioxide at these areas. CONCLUSION: Significant changes were seen in temperature and oxygen content after only 30 min of smoking. The results from this study suggest that alterations in the skin temperature and oxygen content in facial skin after smoking may be an underlying cause of premature skin aging. PMID- 22092970 TI - Expression and regulation of CCL15 by human airway smooth muscle cells. AB - BACKGROUND: Structural cells are an important reservoir of chemokines that coordinate the influx of various immune cells to the lungs of asthmatics. Airway smooth muscle cells (ASMC) are an important source of these chemokines. CCL15 is a recently described chemo-attractant for neutrophils, eosinophils, monocytes and lymphocytes. OBJECTIVE: To determine the production and the regulation of CCL15 by ASMC and to investigate its production in asthmatic airways. METHODS: Human ASMC were obtained from main bronchial airway segments of patients with mild, moderate and severe asthma. To induce chemokine production, cells were incubated with IL-4, IL-13, TNF-alpha or IFN-gamma in presence or absence of dexamethasone, mithramycin A (SP-1 inhibitor) or the IKK-2 inhibitor, AS602868. CCL15 mRNA expression was evaluated by real-time PCR. Immunoreactive CCL15 was detected by immuno-fluorescence and CCL15 protein concentration in the supernatant was measured using ELISA. RESULTS: CCL15 is constitutively expressed in human ASMC and is strongly up-regulated by TNF-alpha. This up-regulation is inhibited by dexamethasone, mithramycin A and AS602868. TNF-alpha-induced CCL15 levels can be synergistically enhanced by the presence of IFN-gamma, at both the transcriptional and translation level. This synergism is NF-kappaB-dependent. Asthmatic biopsies demonstrated higher expression of CCL15 compared with non asthmatic controls. CONCLUSION AND CLINICAL RELEVANCE: Our results show that ASMC are a potent source of CCL15 in the airways and may directly participate in the recruitment of inflammatory cells to asthmatic airways. Targeting the production of CCL15 by ASMC might reduce the inflammatory response within the airways of asthmatic patients. PMID- 22092971 TI - Carbon source control of the phosphorylation state of the Bacillus subtilis carbon-flux regulator Crh in vivo. AB - Bacillus subtilis possesses carbon-flux regulating histidine protein (Crh), a paralog of the histidine protein (HPr) of the phosphotransferase system (PTS). Like HPr, Crh becomes (de)phosphorylated in vitro at residue Ser46 by the metabolite-controlled HPr kinase/phosphorylase HPrK/P. Depending on its phosphorylation state, Crh exerts regulatory functions in connection with carbohydrate metabolism. So far, knowledge on phosphorylation of Crh in vivo has been limited and derived from indirect evidence. Here, we studied the dynamics of Crh phosphorylation directly by non-denaturing gel electrophoresis followed by Western analysis. The results confirm that HPrK/P is the single kinase catalyzing phosphorylation of Crh in vivo. Accordingly, phosphorylation of Crh is triggered by the carbon source as observed previously for HPr, but with some differences. Phosphorylation of both proteins occurred during exponential growth and disappeared upon exhaustion of the carbon source. During exponential growth, ~80% of the Crh molecules were phosphorylated when cells utilized a preferred carbon source. The reverse distribution, i.e. around 20% of Crh molecules phosphorylated, was obtained upon utilization of less favorable substrates. This clear-cut classification of the substrates into two groups has not previously been observed for HPr(Ser)~P formation. The likely reason for this difference is the additional PTS-dependent phosphorylation of HPr at His15, which limits accumulation of HPr(Ser)~P. PMID- 22092972 TI - Evaluation of cortical bone thickness and root proximity at maxillary interradicular sites for mini-implant placement. AB - OBJECTIVES: The purpose of this study was to evaluate the interradicular cortical bone thickness, alveolar process width and root proximity for planning mini implant placement in the maxillary alveolar process. MATERIAL AND METHODS: Eighty maxillae (right and left sides) of 40 Japanese adult skulls were examined. The samples were imaged and measured using a micro-CT system. Buccal and palatal interradicular cortical bone thickness, alveolar process width, and root proximity were measured in six interradicular sites from distal of central incisor to mesial of second molar. Buccal and palatal interradicular cortical bone thickness and alveolar process width were measured at 10 different vertical levels. Root proximity was measured at four different vertical levels. RESULTS: Buccal and palatal interradicular cortical bone thickness and alveolar process width tended to increase from crest to base of alveolar process. The buccal interradicular cortical bone thickness between canine and first premolar or between first premolar and second premolar was the greatest, and between central incisor and lateral incisor was the least. The palatal interradicular cortical bone was significantly thicker than the buccal. The root proximity between second premolar and first molar or first premolar and second premolar was the widest and between central incisor and lateral incisor it was the narrowest. CONCLUSIONS: The findings of this study suggest that recommendations when low dose 3D multislice CT or low dose cone beam imaging is not available, the results of this research may be useful in providing indicators for selecting the design of the placement site. PMID- 22092973 TI - Reimplantation of cultivated human bone cells from the posterior maxilla for sinus floor augmentation. Histological results from a randomized controlled clinical trial. AB - OBJECTIVES: The aim of the present randomized clinical study was to evaluate histologically whether the addition of cultivated, autogenous bone cells to a composite graft of deproteinized bovine bone mineral (DBBM) and autogenous bone (AB) for sinus floor augmentation (SFA) enhance bone formation compared with what achieved after SFA with DBBM + AB alone. MATERIAL AND METHODS: Twenty patients with remaining posterior maxillary alveolar crest height of less than 3 mm received SFA after randomization either with an DBBM and AB composite in a 1 : 1 ratio or with DBBM + AB supplemented with autogenous bone cells, which were cultivated from a bone biopsy harvested earlier from the tuberosity area. Four months after SFA, two cylindrical biopsies were taken from the augmented sinuses concomitantly with the implant site preparation by means of a trephine bur. An additional biopsy was taken from the tuberosity area. Bone density at the augmented sinus and the tuberosity area and the height of augmentation were estimated on non-decalcified histological sections prepared from the biopsies. A relative bone density index (RBD) was also calculated by dividing bone density at the augmented sinus with bone density at the tuberosity area. RESULTS: All patients but one could receive two implants after SFA; in one patient, only one implant could be placed. All implants were osseointegrated and could be loaded. Median bone density in the sinus was 30% and 25% in the cell seeded and no-cells added DBBM + AB groups, respectively. Bone augmentation height averaged 6.0 and 5.4 mm and RBD averaged 0.48 and 0.73 in the cell seeded and no-cells added DBBM + AB groups, respectively. None of the differences between groups was statistically significant. CONCLUSIONS: Cultivated autogenous bone cell seeded to a DBBM + AB composite did not significantly improve bone formation (density and height) after SFA, compared with what was achieved with DBBM + AB alone. Both approaches resulted into enough bone to support implant placement and osseointegration. PMID- 22092974 TI - Five years of experience using a dermal substitute: indications, histologic studies, and first results using a new single-layer tool. AB - BACKGROUND: Dermal substitutes have been used in Europe since 1996 as a mean of reconstructing the dermal layer. OBJECTIVES: To introduce the dermal substitute as a dual-stage reconstructing procedure using the dual-layer version and as a single-stage procedure, combining the single layer with a skin graft to achieve immediate closure. Our further objective was to evaluate the persistence of a commercial dermal substitute in the host's dermal layer using serial histologic studies. MATERIALS AND METHODS: The dermal substitute used was a membrane made using a porous coprecipitate of type I bovine collagen and glycosaminoglycan organized in a three-dimensional structure that allows the host's cell to migrate into it. It is available in a double-layer structure, covered by a silicone sheet, and in a single-layer structure without silicon. RESULTS AND CONCLUSION: We describe the dermal substitute indications in dermatologic surgery and our first results with the single layer as a single-stage procedure with an 80% to 100% take rate. Our histological studies of both products show their perfect integration and the persistence of the peculiar three-dimensional structure (neodermis) 5 years from implantation of the dual-layer dermal substitute. PMID- 22092975 TI - Synergistic use of local flaps for total lower lip reconstruction. PMID- 22092976 TI - Tie-over dressing with criss-cross lacing pattern. PMID- 22092977 TI - Postradiation chronic scalp ulcer: a challenge for wound healing experts. PMID- 22092978 TI - Pitfalls of using dermatoscopy in defining surgical margins of basal cell carcinoma. PMID- 22092979 TI - Recurrence after epidermal grafting in segmental vitiligo. PMID- 22092980 TI - Keratoacanthoma, trauma, and cryotherapy. PMID- 22092981 TI - Radix nasi transposition flap for medial canthus and nasal sidewall defects. PMID- 22092982 TI - The electron beam attenuating properties of SuperFlab, Play-Doh, and wet gauze, compared to plastic water. AB - Bolus material is used commonly with electron treatments. The purpose of this study was to compare the electron beam attenuating properties of SuperFlab, Play Doh, and wet gauze to that of plastic water, and evaluate their characteristics as bolus materials for electron beam therapy. Electron beams of 5, 6, 7, 8, 10, and 12 MeV were used. Dose reduction from a range of bolus thicknesses from 2 mm to a thickness well beyond the thickness required to reach peak ioization was measured for each of the bolus materials to establish independent isodose curves. Measurements performed at the known water Dmax for all bolus materials indicated similar results for SuperFlab and plastic water with less than 3% difference for most energies. Play-Doh resulted in more attenuation or less dose buildup compared with plastic water, especially at lower energies. The difference was as high as 24.7% for the beam energy of 5 MeV for Play-Doh. Evaluation of the dose build up curves for all materials indicated the peak dose build up for wet gauze and Play-Doh occurred at lesser thicknesses compared to plastic water and SuperFlab, particularly at lower energies. If Play-Doh and wet gauze are to be used for electron bolus materials, dose build up curves should be established for the machine being used and the appropriate thickness of bolus material be chosen based on those curves. PMID- 22092983 TI - Key physiological properties contributing to rhizosphere adaptation and plant growth promotion abilities of Azospirillum brasilense. AB - Azospirillum brasilense is a plant growth promoting rhizobacterium (PGPR) that is being increasingly used in agriculture in a commercial scale. Recent research has elucidated key properties of A. brasilense that contribute to its ability to adapt to the rhizosphere habitat and to promote plant growth. They include synthesis of the auxin indole-3-acetic acid, nitric oxide, carotenoids, and a range of cell surface components as well as the ability to undergo phenotypic variation. Storage and utilization of polybetahydroxyalkanoate polymers are important for the shelf life of the bacteria in production of inoculants, products containing bacterial cells in a suitable carrier for agricultural use. Azospirillum brasilense is able to fix nitrogen, but despite some controversy, as judging from most systems evaluated so far, contribution of fixed nitrogen by this bacterium does not seem to play a major role in plant growth promotion. In this review, we focus on recent advances in the understanding of physiological properties of A. brasilense that are important for rhizosphere performance and successful interactions with plant roots. PMID- 22092984 TI - Meeting the national health goal to reduce unintended pregnancy. AB - In spite of advances in health care, the rate of unintended pregnancy has not diminished. Healthy People 2020 and the Affordable Care Act of 2010 have promoted prevention as the most effective means of ensuring the health of the citizens of the United States. This shift in the national approach to the promotion of prevention holds the potential to appropriately address pregnancy planning from a comprehensive public health framework. PMID- 22092985 TI - Effects of frequency on gross efficiency and performance in roller ski skating. AB - The purpose of the present study was to examine the effect of frequency on efficiency and performance during G3 roller ski skating. Eight well-trained male cross-country skiers performed three submaximal 5-min speeds (10, 13, and 16 km/h) and a time-to-exhaustion (TTE) performance (at 20 km/h) using the G3 skating technique using freely chosen, high, and low frequency at all four speeds. All tests were done using roller skis on a large treadmill at 5% incline. Gross efficiency (GE) was calculated as power divided by metabolic rate. Power was calculated as the sum of power against frictional forces and power against gravity. Metabolic rate was calculated from oxygen consumption and blood lactate concentration. Freely chosen frequency increased from 60 to 70 strokes/min as speed increased from 10 to 20 km/h. GE increased with power. At high power (20 km/h performance test), both efficiency and performance were significantly reduced by high frequency. In regard to choice of frequency during G3 roller ski skating, cross-country skiers seems to be self-optimized both in relation to energy saving (efficiency) and performance (TTE). PMID- 22092986 TI - Composition dynamics of epilithic intertidal bacterial communities exposed to high copper levels. AB - Copper has a dual role for organisms, both as micronutrient and toxic element. Copper mining activities have an enormous ecological impact because of the extraction process and the consequent release of copper-containing waste materials to the environment. In northern Chile, mainly in the Chanaral coastal area, this phenomenon is clearly evident. The released waste material has caused a strong modification of the area, and copper enrichment of beaches and rocky shores has provoked a decrease in the richness and diversity of many species of macroorganisms. However, the effects that copper enrichment has on microbial (e.g. bacterial epilithic) communities associated with the rocky shore environment are poorly understood. Using a culture-independent molecular approach, field sampling and laboratory microcosm experiments, we determined the effects of copper enrichment on bacterial communities inhabiting the rocky shore environment. Field samples showed a strong effect of copper on the structure of the natural bacterial epilithic communities, and microcosm experiments demonstrated rapid changes in bacterial community when copper is added, and reversibility of this effect within 48 h after copper is removed. PMID- 22092987 TI - Complementary therapies in rehabilitation: nurses' narratives. Part 1. AB - AIMS AND OBJECTIVES: To document the narratives of nursing staff in a Thai rehabilitation centre where complementary therapies are used and to discuss perceived progress of these complementary therapies on stroke patients. Specific complementary therapies used at this rehabilitation centre include Thai massage and herbal therapies. BACKGROUND: In Thailand, there is cultural acknowledgement of a range of traditional therapies (including complementary therapies) widely used in Thai health care. For example, meditation enjoys wide acceptance in Thai culture and attracts strong participation from visitors to Thai Buddhist centres because of growing interest in developing a personal health regime for future preventative health problems. DESIGN: Qualitative study using narrative inquiry and discourse analysis framed by poststructural theory. METHOD: Six nursing staff and six stroke patients were interviewed about their involvement in complementary therapy practice and treatments and their experiences of these therapies in rehabilitation. This paper reports the six nurses' narratives of their involvement with patients and complementary therapies. RESULTS: The overall findings revealed two strong themes: nurses' professional landscape and changes in stroke patients' embodiment. These two themes were interwoven in a main discourse of nurses attending to and enabling holistic care. CONCLUSION: The contexts of temporality, spatiality and other people influencing the progress of patients' recovery are significant in this study. In particular, the findings illustrate the importance of the nurses' discourse in preparing stroke patients for a state of readiness to heal. RELEVANCE TO CLINICAL PRACTICE: The nurses' role becomes much more significant in health care as demonstrated through these stories. Their part in establishing a holistic approach through motivating, advising, educating, calming and imparting a sense of family enables a strong connection with mind, body and spirit potentiating recovery for stroke patients. PMID- 22092988 TI - Changes in patient flow among five hospitals participating in a learning collaborative. AB - This was an evaluation of the efforts of five hospitals that participated in a collaborative aimed at improving patient flow and reducing emergency department (ED) crowding. Interviews with hospital implementation team members were conducted at two separate times, and multivariate linear regression models and bivariate logistic models were constructed to assess changes in ED length of stay (LOS) and left without being seen (LWBS). By the end of the collaborative, four of the five hospitals had at least one fully implemented improvement strategy. Those hospitals experienced modest improvements in patient flow: a hospital that implemented front-end improvements and devoted additional resources to fast track had a 51-min reduction in ED LOS, another that implemented only front-end improvements had a 9-min reduction in LOS, a third hospital that improved communication between the ED and inpatient units to facilitate admissions decreased LWBS from 0.6% to 0.4%, and a fourth hospital reduced LOS by 59 min for mid-acuity patients by establishing a new care process for them. Results suggest that relatively small changes may lead to improvements in measures of patient flow that are modest, at best. PMID- 22092989 TI - Myeloperoxidase-positive acute megakaryoblastic leukemia in a dog. AB - A 16-month-old female spayed Labrador Retriever was referred to the University of Edinburgh for exercise intolerance, inappetence, and severe anemia. A CBC showed severe nonregenerative anemia and moderate numbers of atypical cells with morphologic features most consistent with megakaryoblastic origin. Similar cells were identified in a bone marrow aspirate and accounted for 23% of all nucleated cells. Atypical promegakaryocytes and megakaryocytes were also noted. Myelodysplastic syndrome affecting the megakaryocytic lineage was suspected. Cytologic examination of a fine-needle aspirate of the spleen revealed rare megakaryoblasts similar to those in blood and bone marrow. At necropsy, the bone marrow consisted of atypical megakaryoblasts and megakaryocytes that were also infiltrating spleen, liver, lymph nodes, renal perihilar tissue, and visceral adipose tissue, consistent with acute megakaryoblastic leukemia. Immunohistochemical analysis of splenic sections confirmed megakaryoblastic origin (immunoreactive for CD61 and von Willebrand factor). Some leukemic cells were also immunoreactive for myeloperoxidase (MPO). This aberrant immunophenotype suggested both megakaryocytic and granulocytic/monocytic differentiation of the leukemic cells. To our knowledge, this is the first report of MPO-positive acute megakaryoblastic leukemia in a dog. PMID- 22092990 TI - Bacterial leakage along the implant-abutment interface: culture and DNA Checkerboard hybridization analyses. AB - OBJECTIVE: Bacterial species have been found harboring the internal surface of dental implants as consequence of their failed connections. The aim of the present study was to compare the detection frequency of bacterial leakage from human saliva through the implant-abutment interface, under non-loading conditions, using either DNA Checkerboard or culture method. MATERIALS AND METHODS: Thirty dental implants with hexagonal platforms were connected to pre machined abutments according to the manufacturers' specifications. The assemblies were individually incubated in human saliva under anaerobic conditions for 7 days at 37 degrees C. Afterward, contents from the inner parts of the implants were collected and evaluated with either DNA Checkerboard (s = 15) or culture (n = 15). Subsequently, identification and quantitation of bacterial species from saliva and implants were carried out for the group evaluated with the DNA Checkerboard method. RESULTS: Both DNA Checkerboard and culture showed positive signals of bacterial leakage in 6 of the 15 evaluated samples. Capnocytophaga gingivalis and Streptococcus mutans were the most frequently detected species harboring the internal surface of the implants followed by Veillonella parvula. CONCLUSION: Occurrence of bacterial leakage along the implant-abutment interface is comparably detected with both DNA Checkerboard hybridization and conventional culture methods. PMID- 22092991 TI - Soft tissue surrounding switched platform implants: an immunohistochemical evaluation. AB - OBJECTIVES: This clinical and immunohistochemical study was designed to characterize the cellular and molecular patterns for bone loss of soft tissues surrounding implants restored with different implant platform configurations. MATERIAL AND METHODS: A total of 32 implants were restored using abutments with the following mismatches: 0 mm (control group), 0.25 mm (test group(1)), 0.5 mm (test group(2)) and 0.85 mm (test group(3)). Four years after, loading all sites were clinically healthy, and soft tissue samples were harvested and processed for immunohistochemical analysis. Amounts of lymphocytes T (LyT) -B (LyB), IL-17 and RANKL were assessed. RESULTS: No significant difference was found between groups (P > 0.05) in terms of infiltrated T and B cell counts, IL-17 and RANKL expressions. When pooled data were analysed, lymphocytes T counts and IL-17 were higher than lymphocytes B counts and RANKL. LyT and LyB counts were highly negatively correlated (Pearson's r > 0.7) and IL-17 was correlated (Pearson's r > 0.4, <0.7) to LyT and LyB. CONCLUSIONS: After prolonged exposure of abutments in the oral cavity, the configuration of the implant abutment interface does not seem to affect the inflammatory cellular and molecular pattern responsible for bone loss. PMID- 22092992 TI - Fitness testing as a discriminative tool for the diagnosis and monitoring of fibromyalgia. AB - We aimed to determine the ability of a set of physical fitness tests to discriminate between presence/absence of fibromyalgia (FM) and moderate/severe FM. The sample comprised 94 female FM patients (52 +/- 8 years) and 66 healthy women (54 +/- 6 years). We assessed physical fitness by means of the 30-s chair stand, handgrip strength, chair sit and reach, back scratch, blind flamingo, 8 feet up and go, and 6-min walking tests. Patients were classified as having moderate FM if the score in the Fibromyalgia Impact Questionnaire (FIQ) was <70 and as having severe FM if the FIQ was >=70. FM patients and patients with severe FM performed worse in most of the fitness tests studied (P < 0.001). Except the back scratch test, all the tests were able to discriminate between presence and absence of FM [area under the curve (AUC) = 0.66 to 0.92; P <= 0.001], and four tests also discriminated FM severity (AUC = 0.62 to 0.66; P <= 0.05). The 30-s chair stand test showed the highest ability to discriminate FM presence and severity (AUC = 0.92, P < 0.001; and AUC = 0.66, P = 0.008, respectively), being the corresponding discriminating cutoffs 9 and 6 repetitions, respectively. Physical fitness in general, and particularly the 30-s chair stand test, is able to discriminate between women with FM from those without FM, as well as between those with moderate FM from their peers with severe FM. PMID- 22092993 TI - Effects of adhesive dressings on stratum corneum conductance. AB - BACKGROUND: Stratum corneum is a fundamental layer of epidermis. It acts as a barrier, with antimicrobial features, regulating skin permeability and integrity as well. Adhesive dressings and their removal could alter this layer, affecting cutaneous water balance and lipid composition of stratum corneum. These changes could be monitored by measurement of cutaneous hydration. METHODS: Ninety-two patients affected by wounds dressed with adhesive tapes or plasters have been studied. Measurement of skin conductance under tape/plaster and in the surrounding healthy skin, immediately after removal of dressing has been performed. Dressing age, wound localization, and characteristics were also considered. RESULTS: Adhesive dressings alter significantly stratum corneum conductance. Although healthy skin hydration has significant variations throughout the body, cutaneous conductance under adhesive dressing in different areas displays no significative changes. Moreover, the increase in hydration due to adhesive tapes/plasters showed no association with wound dehiscence. DISCUSSION: Adhesive dressings cause a significative increase in stratum corneum conductance, acting as a barrier to apocrine secretions. Although different hydration levels have been observed in healthy skin throughout the body, no difference exists under adhesive dressing among different regions, suggesting no contraindications in their employment throughout the body. CONCLUSION: Increase in cutaneous hydration showed no correlations with wound dehiscence, thus confirming safety and practicality of these dressings. PMID- 22092994 TI - The RANKL-OPG system in clinical periodontology. AB - BACKGROUND AND OBJECTIVES: The receptor activator of NF-kappaB ligand osteoprotegerin (RANKL-OPG) bi-molecular system is the "bottle-neck" regulator of osteoclastogenesis and bone resorption, both in physiological and pathological conditions. This review aims to elaborate the current knowledge on RANKL and OPG in periodontal disease, and to evaluate their diagnostic and prognostic potential as biomarkers of the disease. MATERIALS AND METHODS: To pursue this aim, electronic and manual searches were performed for identifying clinical and in vivo studies on RANKL and OPG in gingival tissue, gingival crevicular fluid, saliva and blood. Smoking and diabetes mellitus were also considered for their potential effects. RESULTS: Papers fulfilling the inclusion criteria demonstrate that RANKL is up-regulated, whereas OPG is down-regulated in periodontitis, compared to periodontal health, resulting in an increased RANKL/OPG ratio. This ratio is further up-regulated in smokers and diabetics, and is not affected by conventional periodontal treatment. CONCLUSIONS: The increased RANKL/OPG ratio may serve as a biomarker that denotes the occurrence of periodontitis, but may not necessarily predict on-going disease activity. Its steadily elevated levels post treatment may indicate that the molecular mechanisms of bone resorption are still active, holding an imminent risk for relapse of the disease. Additional adjunct treatment modalities that would "switch-off" the RANKL/OPG ratio may therefore be required. PMID- 22092995 TI - Orally administered heat-killed Lactobacillus gasseri TMC0356 can upregulate cell-mediated immunity in senescence-accelerated mice. AB - The present study was conducted to test the ability of probiotic lactobacilli to alter age-related immunosenescence in host animals. Senescence-accelerated mouse prone 1 mice were orally fed heat-killed Lactobacillus gasseri TMC0356 (TMC0356) for 4 and 8 weeks at dosages of 10 mg day(-1) after a 16-week period of prefeeding with a standard diet. After 4 and 8 weeks of TMC0356 intervention, splenic activation of natural killer (NK) cells and mRNA expression of cytokines and other immune molecules in the lungs were analysed. After 4 and 8 weeks, splenic NK cell activities were significantly higher in the TMC0356-fed mice compared with control mice (P < 0.05). After 4 weeks, mRNA expression of interleukin-2 and interferon-(alpha and beta) receptor 1 in lung cells isolated from the TMC0356-fed mice also increased significantly compared with that in lung cells from the control mice (P < 0.05). These results suggest that lactobacilli, especially certain selected strains, might enhance cell-mediated immunity in host animals and thereby alter age-related immunosenescence. PMID- 22092996 TI - Bet v 1-like pollen allergens of multiple Fagales species can sensitize atopic individuals. AB - BACKGROUND: In the temperate climate zone of the Northern hemisphere, Fagales pollen allergy represents the main cause of winter/spring pollinosis. Among Fagales trees, pollen allergies are strongly associated within the Betulaceae and the Fagaceae families. It is widely accepted that Fagales pollen allergies are initiated by sensitization against Bet v 1, the birch pollen major allergen, although evidence is accumulating that the allergenic activity of some Bet v 1 like molecules has been underestimated. OBJECTIVE: To investigate the allergenic potential of the clinically most important Fagales pollen allergens from birch, alder, hazel, hornbeam, hop-hornbeam, oak, beech and chestnut. METHODS: To obtain the full spectrum of allergens, the three previously unavailable members of the Bet v 1-family, hop-hornbeam Ost c 1, chestnut Cas s 1 and beech Fag s 1, were identified in the respective pollen extracts, cloned and produced as recombinant proteins in E. coli. Together with recombinant Bet v 1, Aln g 1, Car b 1, Cor a 1 and Que a 1, the molecules were characterized physicochemically, mediator release assays were performed and IgE cross-reactivity was evaluated by ELISA and Immuno Solid-phase Allergen Chip (ISAC) IgE inhibition assays. RESULTS: All allergens showed the typical Bet v 1-like secondary structure elements, and they were all able to bind serum IgE from Fagales allergic donors. Strong IgE binding was observed for Betuloideae and Coryloideae allergens, however, cross-reactivity between the two subfamilies was limited as explored by inhibition experiments. In contrast, IgE binding to members of the Fagaceae could be strongly inhibited by serum pre-incubation with allergens of the Betuloideae subfamily. CONCLUSIONS AND CLINICAL RELEVANCE: The data suggest that Bet v 1-like allergens of the Betuloideae and Coryloideae subfamily might have the potential to induce IgE antibodies with different specificities, while allergic reactions towards Fagaceae allergens are the result of IgE cross-reactivity. PMID- 22092997 TI - An explorative study of non-invasive ultra-weak photon emission and the anti oxidative influence of oral zinc sulphate in light-sensitive patients with erythropoietic protoporphyria. AB - BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare, inherited disorder of haem biosynthesis owing to deficient ferrochelatase (FECH) and accumulation of protoporphyrin IX (PPIX). This results in acute cutaneous photosensitivity upon light exposure with production of reactive oxygen species (ROS) and ultra-weak photon emission (UPE) as a by-product. We investigated if UPE evaluated the light sensitivity in EPP patients and influence of zinc treatment. METHODS: Fourteen EPP patients took zinc sulphate (3 * 200 mg/day) during spring and summer. Using a photomultiplier (PM), UPE was measured from the buttock skin and dorsal hand before and after solar-simulated light (SUN) exposure. Blood samples were analysed routinely for plasma zinc, iron, ferritin, transferrin, haemoglobin, erythrocyte PPIX and Zn-PPIX. RESULTS: UPE in EPP patients resembled that seen in healthy individuals. Without treatment, a seasonal decrease was seen from spring to summer in four control patients. However, oral zinc treatment reduced ROS formation significantly regardless of SUN exposure. After SUN exposure, the initial burst was correlated to plasma iron and erythrocyte PPIX. During treatment, an inverse correlation was found between plasma zinc concentration and the initial burst. CONCLUSION: Measurements of UPE can be used for monitoring UVA induced oxidative processes in vivo in the skin of EPP patients. PMID- 22092998 TI - An investigation of nursing students' experiences in an Iranian psychiatric unit. AB - This qualitative study aimed to investigate and explain clinical experiences of nursing students in a psychiatric unit in an Iranian hospital. The researcher performed a Heideggerian hermeneutic phenomenological study by conducting in depth interviews of 13 participants. An analysis based on Diekelmann's method helped to interpret the data and uncover common themes. The following four correlated themes were obtained: anxiety, maturation, dissatisfaction and enthusiasm. These results present distinctive insights on contextualizing, developing and implementing clinical education in Iran, especially in psychiatric units. The exploration and description of students' experiences will help nurse educators to plan the clinical learning opportunities such that they are less stressful, thus ensuring that nursing students are equipped to act as therapeutic professionals. PMID- 22092999 TI - Widespread use of real-time PCR for rickettsial diagnosis. AB - We report 2 years of experience with rickettsial molecular diagnosis using real time PCR at the French National Reference Center. All Rickettsia genomes available were compared to discover specific sequences to design new sets of primers and probes. The specificity was verified in silico and against a panel of 30 rickettsial species. Sensitivity was determined using 10-fold serial dilutions. Finally, primers and probes that were both specific and sensitive were routinely used for the diagnosis of rickettsial infections from clinical specimens. We retained sets of primers and probes to detect spotted fever group Rickettsia, typhus group Rickettsia,Rickettsia conorii,Rickettsia slovaca,Rickettsia africae and Rickettsia australis; 643 clinical samples were screened for the presence of Rickettsia DNA. Overall, 45 positive samples were detected, including 15 Rickettsia africae, nine R. conorii, five Rickettsia sibirica mongolitimonae, four R. slovaca, two R. australis, four Rickettsia massiliae, one Rickettsia honei, one Rickettsia typhi and eight Rickettsia sp. Positive samples were detected mainly from cutaneous biopsies and swabs (31/45). Widespread use of real-time PCR is inexpensive and reduces delay in the diagnosis of rickettsial infections. These real-time PCR assays could be implemented easily in laboratories that have molecular facilities and may be added to existing molecular tools as a point-of-care strategy. PMID- 22093000 TI - Community-specific pH response of denitrification: experiments with cells extracted from organic soils. AB - Denitrifying prokaryotes are phylogenetically and functionally diverse. Little is known about the relationship between soil denitrifier community composition and functional traits. We extracted bacterial cells from three cultivated peat soils with contrasting native pH by density gradient centrifugation and investigated their kinetics of oxygen depletion and NO2 -, NO, N(2) O and N(2) accumulation during initially hypoxic batch incubations (0.5-1 MUM O(2)) in minimal medium buffered at either pH 5.4 or 7.1 (2 mM glutamate, 2 mM NO3 -). The three communities differed strikingly in NO2 - accumulation and transient N(2) O accumulation at the two pH levels, whereas NO peak concentrations (24-53 nM) were similar across all communities and pH treatments. The results confirm that the communities represent different denitrification regulatory phenotypes, as indicated by previous denitrification bioassays with nonbuffered slurries of the same three soils. The composition of the extracted cells resembled that of the parent soils (PCR-TRFLP analyses of 16S rRNA genes, nirK, nirS and nosZ), which were found to differ profoundly in their genetic composition (Braker et al., ). Together, this suggests that direct pH response of denitrification depends on denitrifier community composition, with implications for the propensity of soils to emit N(2) O to the atmosphere. PMID- 22093001 TI - Fate of autologous and fresh-frozen allogeneic block bone grafts used for ridge augmentation. A CBCT-based analysis. AB - OBJECTIVES: To evaluate dimensional changes in autologous (AT) and fresh-frozen allogeneic (AL) block bone grafts 6 months after alveolar ridge augmentation. MATERIAL AND METHODS: Twenty-six partially or totally edentulous patients treated either with fresh-frozen AL bone or AT bone onlay block grafts prior to implant placement (13 patients in each group), were included in this analysis. Patients received CBCT (i-CAT Classic) examinations prior to surgery and 14 days and 6 months after grafting. Differences in alveolar ridge area among the various observation times were evaluated by planimetric measurements on two-dimensional CBCT images of the grafted regions. Nineteen grafted blocks from each group were evaluated. RESULTS: Significant increase in alveolar ridge dimensions, allowing implant placement, was obtained with both types of grafts 6 months after grafting; no significant differences in alveolar ridge area were observed between the groups at the various observation times. However, graft resorption in the AL group was significantly larger compared to that in the AT group at 6 months. CONCLUSIONS: Larger bone graft resorption was seen in patients treated with fresh frozen AL bone than in those treated with AT bone 6 months following alveolar ridge augmentation. PMID- 22093002 TI - White globules in melanocytic neoplasms: in vivo and ex vivo characteristics. PMID- 22093003 TI - Inflammation and remodelling patterns in early stage chronic rhinosinusitis. AB - BACKGROUND: A distinct set of inflammatory and remodelling factors have been found elevated in chronic rhinosinusitis. OBJECTIVE: The investigation of their expression in early stage disease may reveal early events in this common disease. METHODS: Sinonasal mucosal samples from nine patients with early stage CRSsNP were taken from the inferior and middle turbinates, the uncinate process, maxillary sinus, anterior ethmoid, bulla ethmoidalis and the posterior ethmoid and measured for TGF-beta 1 and it's receptors, MPO protein as well as pro inflammatory cytokines (TNF-alpha and IL-1beta) and the Th1 cell signature (IFN gamma and T-bet). As outcome parameter for TGF-beta signalling collagen deposition was analysed. Inferior turbinates from patients undergoing (rhino-) septoplasty were collected as controls. RESULTS: TGF-beta 1 protein concentrations were significantly increased in the maxillary sinuses (P = 0.006), the uncinate process (P = 0.01), the anterior ethmoid including the bulla ethmoidalis (P = 0.005) and the posterior ethmoid (P = 0.037) when compared to the inferior and middle turbinates. Collagen deposition was significantly increased in the maxillary sinus when compared to the inferior turbinates (P = 0.008). In contrast, mRNA for TGF-beta receptors, Th1 related markers (IFN-gamma and T-bet), pro-inflammatory cytokines (IL-1 beta and TNF-alpha), and MPO protein as neutrophil marker were expressed at all locations but showed no significant differences between the various locations. TGF-beta 1 mRNA expression in inferior turbinates of CRSsNP was significantly higher when compared to inferior turbinates of controls (P = 0.017). The pro-inflammatory cytokines and Th1 related cytokines did not show an upregulation in inferior turbinates of CRSsNP when compared to controls. CONCLUSIONS: In early stage chronic sinus disease, TGF beta protein is expressed in significantly higher concentrations within the paranasal sinuses when compared to turbinates, whereas pro-inflammatory, neutrophilic and Th1 markers did not show any difference. These findings suggest that TGF-beta plays a central role in the initiation of CRSsNP, and represents a major target for further research and future intervention. PMID- 22093004 TI - Differential photoinhibition of bacterial and archaeal ammonia oxidation. AB - Inhibition by light potentially influences the distribution of ammonia oxidizers in aquatic environments and is one explanation for nitrite maxima near the base of the euphotic zone of oceanic waters. Previous studies of photoinhibition have been restricted to bacterial ammonia oxidizers, rather than archaeal ammonia oxidizers, which dominate in marine environments. To compare the photoinhibition of bacterial and archaeal ammonia oxidizers, specific growth rates of two ammonia oxidizing archaea (Nitrosopumilus maritimus and Nitrosotalea devanaterra) and bacteria (Nitrosomonas europaea and Nitrosospira multiformis) were determined at different light intensities under continuous illumination and light/dark cycles. All strains were inhibited by continuous illumination at the highest intensity (500 MUE m(-2) s(-1)). At lower light intensities, archaeal growth was much more photosensitive than bacterial growth, with greater inhibition at 60 MUE m(-2) s( 1) than at 15 MUE m(-2) s(-1), where bacteria were unaffected. Archaeal ammonia oxidizers were also more sensitive to cycles of 8-h light/16-h darkness at two light intensities (60 and 15 MUE m(-2) s(-1)) and, unlike bacterial strains, showed no evidence of recovery during dark phases. The findings provide evidence for niche differentiation in aquatic environments and reduce support for photoinhibition as an explanation of nitrite maxima in the ocean. PMID- 22093005 TI - Adjunctive daily supplementation with encapsulated fruit, vegetable and berry juice powder concentrates and clinical periodontal outcomes: a double-blind RCT. AB - AIM: A double-blind randomized controlled trial to determine whether dietary supplementation with fruit/vegetable/berry juice powder concentrates, simultaneously with non-surgical periodontal therapy, improved 2-month treatment outcomes. METHODS: Volunteers with chronic periodontitis were randomly assigned to one of three groups: fruit/vegetable (FV), fruit/vegetable/berry (FVB) or placebo. Supplements were taken daily during non-surgical debridement and maintenance and outcomes assessed at 2, 5 and 8 months after completion. Primary outcomes were mean probing pocket depth (PPD), clinical attachment gain, % sites bleeding on probing (% BOP) at 2 months. Adherence and plasma beta-carotene were determined. RESULTS: Sixty-one nutritionally replete (by serum biochemistry) volunteers enrolled and 60 (n = 20 per arm) completed the 2-month review. Clinical outcomes improved in all groups at 2 months, with additional improvement in PPD versus placebo for FV (p < 0.03). Gingival crevicular fluid volumes diminished more in supplement groups than placebo (FVB; p < 0.05) at 2 months, but not at later times. The % BOP (5 months) and cumulative plaque scores (8 months) were lowered more in the FV group (p < 0.05). CONCLUSIONS: Adjunctive juice powder concentrates appear to improve initial pocket depth reductions in nutritionally replete patients, where plasma micronutrient bioavailability is attainable. Definitive multicentre studies in untreated and treated patients are required to ascertain the clinical significance of such changes. PMID- 22093006 TI - Baby oil therapy for uremic pruritus in haemodialysis patients. AB - AIMS: The purpose of this study was to investigate the effectiveness of chilled/un-chilled baby oil therapy for treating uremic pruritus in haemodialysis patients. BACKGROUND: Uremic pruritus affects 50-90% of haemodialysis patients, which makes it one of the most common medical problems in this population. Pruritus can cause skin infection, desquamation, pathological skin change, sleep disorder, anxiety, depression and social dysfunction. DESIGN: A prospective, pretest-post-test quasi-experimental design was used. METHODS: Haemodialysis patients with uremic pruritus were recruited and randomly assigned to one of three groups: experimental group 1 (chilled baby oil treatment; n = 30), experimental group 2 (un-chilled baby oil treatment; n = 31) and a control group (routine care only; n = 32). Participants in experimental group 1 and experimental group 2 were treated with chilled and un-chilled baby oil, respectively, for 15 minutes at least once daily for three weeks. The control group received no intervention other than standard care. Data collection included demographic data and itch severity. Medical records were also reviewed. RESULTS: The baseline characteristics of subjects in this study were as follows: 59% were male, mean age was 61.88 (SD 12.7) years, mean duration of haemodialysis was 5.31 years, mean duration of uremic pruritus was 40.58 (SD 37.8) months and mean intensity of uremic pruritus was mild. The anti-pruritic effects were significantly larger in subjects treated with either chilled or un-chilled baby oil than in those who received routine care. Anti-pruritic effects did not significantly differ between experimental group 1 and experimental group 2. CONCLUSIONS: The study confirmed that, for relieving pruritus in haemodialysis patients, either chilled or un-chilled baby oil is as effective as moisturising lotions and cooling soothing agents. RELEVANCE TO CLINICAL PRACTICE: Applying baby oil is a simple, safe, inexpensive and easily administered treatment for itchy skin in haemodialysis patients. By preventing or reducing uremic pruritus, baby oil treatment may also improve quality of life in this patient group. PMID- 22093008 TI - The clinical evaluation of penicillin allergy: what is necessary, sufficient and safe given the materials currently available? PMID- 22093009 TI - Unravelling gene-by-environment effects in asthma and allergy: the glutathione pathway as an early success story. PMID- 22093010 TI - A statement on cefazolin immediate hypersensitivity: data from a large database, and focus on the cross-reactivities. AB - BACKGROUND: More perioperative cefazolin use has resulted in an increased risk of cefazolin-associated reactions. OBJECTIVE: The aim of this article is to study immediate reactions to cefazolin and attempt to determine possible allergic cross reactivity with other beta-lactams using data from the Drug Allergy and Hypersensitivity Database (DAHD). METHODS: All 25 cefazolin-associated reactions in the DAHD were reviewed. The cases identified were then investigated according to the European Network for Drug Allergy (ENDA) recommendations by skin testing and challenges. RESULTS: A total of 10 individuals with proven IgE-mediated cefazolin hypersensitivity were identified between January 1999 and July 2009. All the index reactions were compatible with an acute IgE-mediated process, six with anaphylaxis, two with systemic allergic reactions without hypotension, and two with urticaria/angioedema. Cefazolin skin tests were positive in seven individuals and cefazolin challenges were positive in three more individuals. In the eight cefazolin allergic patients who had challenges with other beta-lactams, there was no positive reaction noted. CONCLUSION AND CLINICAL RELEVANCE: In this cohort of patients with IgE-mediated reactions to cefazolin, a majority tolerated amoxicillin and several patients tolerated other cephalosporins. This implies that the R1 side-chain may play an essential role in IgE-mediated reactions to cefazolin. No clear rule to predict cross-reactivity with other beta-lactams could be determined. More research on IgE-mediated hypersensitivity to cefazolin and other cephalosporins is needed. PMID- 22093011 TI - Effective treatment of experimental ragweed-induced asthma with STAT-6-IP, a topically delivered cell-penetrating peptide. AB - BACKGROUND: Treatment of allergic airways disease including asthma remains primarily local immunosuppression with topical corticosteroid and symptomatic management with antihistamines and anti-leucotrienes. We have developed a novel topical therapy designed to specifically inhibit the events associated with Th2 cell activation. OBJECTIVE: We assessed the efficacy of our cell-penetrating STAT 6 inhibitory peptide (STAT-6-IP), a novel treatment for allergic airways disease, in a model of chronic ragweed-induced asthma. METHODS: Six- to eight-week-old mice were sensitized over 5 weeks with intranasal (IN) exposures to whole ragweed allergen without adjuvant. Mice were then IN challenged with Amba 1 with and without treatment IN with STAT-6-IP and allergic responses assessed. Two weeks later, some animals were rechallenged with Amba 1 with or without STAT-6-IP. RESULTS: Animals exposed to IN ragweed developed significant airway hyperresponsiveness and airways inflammation upon challenge. Cell cultures showed increases in Th2 cytokines IL-4 and IL-13. Topical STAT-6-IP treatment reduced production of Th2 cytokines, demonstrated increased expression of IL-10 and reduced frequency of cultured IL-4 positive CD4+ T cells derived from treated mice, suggesting that STAT-6-IP treatment may be immunomodulatory. Airway responsiveness to methacholine challenge in the treatment group was similarly reduced to that of the non-allergic PBS-exposed animals. Importantly, STAT-6-IP treated mice remained hyporesponsive following second ragweed challenge 2 weeks after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that topical application of the STAT-6-IP is sufficient to inhibit allergic airways responses in animals chronically sensitized and challenged with ragweed. Data show that a single topical treatment course is sufficient to block signs of allergic responses to ragweed in the airways for at least 2 weeks. STAT-6-IP is a novel potential treatment for chronic allergic asthma. PMID- 22093013 TI - Dimensions of buccal bone and mucosa at immediately placed implants after 7 years: a clinical and cone beam computed tomography study. AB - OBJECTIVE: The objective of this study was to evaluate the dimensions of buccal bone and soft tissue at immediately placed implants over a 7-year period. MATERIAL AND METHODS: Twenty-four patients, that participated in a clinical prospective study and received implants immediately placed into extraction socket, were enrolled for this study. Residual bone defects were grafted with xenogenic bone substitute and covered by means of collagen membrane. Baseline examination included measurements of full-mouth plaque and bleeding scores, width of keratinized mucosa, and dimensions of residual bone defects at the buccal aspect. Seven years after implant placement, full-mouth plaque score, full-mouth bleeding score, width of keratinized mucosa, and probing pocket depth were assessed and cone beam computed tomography images acquired. Dimensions of buccal bone and soft tissue were evaluated on the cross-sectional cone beam computed tomography reconstructions. Differences between two time-points were tested using the two-sided t-test. Correlation analysis was used to investigate the influence of baseline bone defect dimensions on the bone dimensions measured at the 7-year follow-up. RESULTS AND CONCLUSIONS: Fourteen patients attended the follow-up examination. In five implants almost no buccal bone was detected, whereas in the remaining nine implants the buccal bone was found covering the rough implant surface. No correlation was found between initial bone defects and bone dimensions at the follow-up examination. The sites without radiographically detectable buccal bone at the 7-year control presented with 1 mm more apical mucosal level in comparison to implants with intact buccal bone. PMID- 22093014 TI - Experimental evidence for interfacial biochemical bonding in osseointegrated titanium implants. AB - OBJECTIVES: (i) To identify and quantify an interfacial biochemical bond and the bonding strength of osseointegrated implants with bioactive titanium oxide chemistry, ATiO(x)B (A, metal cations; TiO(x) , titanium oxides/hydroxides; B, non-metal anions) and (ii) to provide quantitative evidence for the biochemical bond theory of osseointegration proposed by Sul et al. for description and explanation of why and how the implants with ATiO(x) B surface oxide chemistry may exhibit a significantly stronger bone response, in spite of the fact that the roughness values approached zero, or were equivalent to or significantly lower than those of the control implants. MATERIALS AND METHODS: We applied a newly developed biochemical bond measurement (BBM) method to model implant surfaces that were "perfectly" smooth nanotopography near-zero roughness as the constant parameter, and used the bioactive surface chemistry of titanium oxide, ATiOx B chemistry as a variable parameter in rabbit tibiae for 10 weeks. In this manner, we determined an interfacial biochemical bond and quantified its bonding strength. RESULTS: The increase in biochemical bond strengths of the test implant relative to the control implant was determined to be 0.018 (+/-0.008) MPa (0.031 vs 0.021 MPa, n = 10) for tensile strength and 8.9 (+/-6.1) Ncm (33.0 vs 24.1 Ncm, n = 10) for removal torque. Tensile and removal torque show strong correlation in the Pearson test (r = 0.901, P <= 0.001). In addition, histomorphometric measurements including bone-to-metal-contact (BMC, P = 0.007), bone area and newly formed bone showed significant increases in the mean values for ATiO(x) B chemistry (P = 0.007, n = 10). Biochemical bond theory states that the surface oxide chemistry, ATiO(x) B must have more electrical and chemical molecular polarity that fractionally charges the surfaces denoted as delta(+) and delta(-) and leads to electrostatic and electrodynamic interactions with the bone healing cascade, eventually leading to the formation of biochemical bonding at the bone/implant interface. CONCLUSIONS: The present study has provided quantitative evidence for biochemical bond theory of osseointegration of implants with bioactive surface oxide chemistry, ATiO(x) B. The theory of biochemical bonds may provide a scientific rationale pertinent to recent emerging trends and technologies for surface chemistry modifications of implants. PMID- 22093015 TI - Caring for women with unintended pregnancies. AB - Unintended pregnancy is a common reproductive health event. Professional responsibilities for nurses providing care to women with unintended pregnancies include appropriate assessment, options counseling, provision of or referral for desired services, care coordination, and prevention efforts aimed at decreasing future unintended pregnancies. Nurses' awareness of available services and their involvement in referring or providing services is an essential component to reproductive health care. PMID- 22093016 TI - Can we define a tolerable level of risk in food allergy? Report from a EuroPrevall/UK Food Standards Agency workshop. AB - BACKGROUND: There is an emerging consensus that, as with other risks in society, zero risk for food-allergic people is not a realistic or attainable option. Food allergy challenge data and new risk assessment methods offer the opportunity to develop quantitative limits for unintended allergenic ingredients which can be used in risk-based approaches. However, a prerequisite to their application is defining a tolerable level of risk. This requires a value judgement and is ultimately a 'societal' decision that has to involve all relevant stakeholders. OBJECTIVE: The aim of the workshop was to bring together key representatives from the stakeholders (regulators, food industry, clinical researchers and patients), and for the first time ever discuss the definition of a tolerable level of risk with regard to allergic reactions to food. RESULTS: The discussions revealed a consensus that zero risk was not a realistic option and that it is essential to address the current lack of agreed action levels for cross-contamination with allergens if food allergen management practice is to be improved. The discussions also indicated that it was difficult to define and quantify a tolerable level of risk, although both the clinical and the industry groups tried to do so. A consensus emerged that doing nothing was not a viable option, and there was a strong desire to take action to improve the current situation. CONCLUSIONS AND CLINICAL RELEVANCE: Two concrete actions were suggested: (1) Action levels should be derived from the data currently available. Different scenarios should be examined and further developed in an iterative process. On the basis of this work, a tolerable level of risk should be proposed. (2) 'One-dose' clinical trial with a low challenge dose should be performed in multiple centres to provide additional information about the general applicability of dose-distribution models and help validate the threshold levels derived. PMID- 22093017 TI - The use of delayed gadolinium enhanced magnetic resonance imaging of cartilage and T2 mapping to evaluate articular cartilage in the normal canine elbow. AB - Commonly used diagnostic tools used to evaluate articular cartilage lack the sensitivity, specificity, and objectivity to measure early changes associated with osteoarthritis. Two techniques using magnetic resonance (MR) imaging have been developed to detect the biology of articular cartilage are delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) and T2 mapping. Both techniques have been validated and are used to study the degenerative and adaptive nature of articular cartilage in people. The use of these techniques as a diagnostic tool in dogs has not been well described. We evaluated articular cartilage in the region of the medial coronoid process (MCP) of six healthy dogs free of detectable orthopedic disease using both MR imaging techniques. Histology and proteoglycan (PG) content of the MCP were used to confirm normal articular cartilage. All dogs had ground reaction forces consistent with normal function. Mean dGEMRIC index (T1 value) was 400 +/- 47 ms and mean T2 value was 56 +/- 8 ms. Intra- and interobserver variability was low. dGEMRIC and T2 values for normal cartilage in the elbow of the dog can be generated reproducibly using 3T MR imaging. Using these techniques as objective outcome measures for clinical studies in dogs with OA conditions should help delineate the efficacy of some disease interventions. PMID- 22093018 TI - A longitudinal investigation of sports-related risk factors for disordered eating in aesthetic sports. AB - Previous studies have indicated a higher risk of disordered eating in certain types of elite sports such as aesthetic sports (e.g., rhythmical gymnastics, figure skating). But even though some studies on risk factors for disordered eating in sports exist, most research on this topic is based on cross-sectional data with limitations on causal inferences. We examined sports-related risk factors for disordered eating in a 1-year longitudinal study with two assessment points. The participants were 65 adolescent athletes from aesthetic sports (mean age 14.0 +/-.2.2 years) who completed measures of disordered eating, social pressure from the sports environment, sports-related body dissatisfaction, desire to be leaner to improve sports performance, and emotional distress resulting from missed exercise sessions. All variables were relatively stable in the mean. Individual changes in the desire to be leaner to improve sports performance were associated with individual changes in disordered eating. Furthermore, a cross lagged partial correlation analysis showed that the desire to be leaner to improve sports performance was predictive of disordered eating and not vice versa. The results of our study indicate that athletes are more at risk for disordered eating if they believe it is possible to enhance their sports performance through weight regulation. PMID- 22093019 TI - Reliability and fatigue failure modes of implant-supported aluminum-oxide fixed dental prostheses. AB - OBJECTIVES: To investigate failure modes and reliability of implant-supported aluminum-oxide three-unit fixed dental prostheses (FDPs) using two different veneering porcelains. MATERIAL AND METHODS: Thirty-six aluminum-oxide FDP frameworks were computer-aided designed and computer-aided manufactured and either hand-veneered(n = 18) or over-pressed(n = 18). All FDPs were adhesively luted to custom-made zirconium-oxide-abutments attached to dental implant fixtures (regular platform 4 * 13 mm). Specimens were stored in water before mechanical testing. A step-stress accelerated life test (SSALT) with three load/cycles varying profiles was developed based on initial single-load-to failure testing. Failure was defined by veneer chipping or chipping in combination with framework fracture. SSALT was performed on each FDP inclined 30 degrees with respect to the applied load direction. For all specimens, failure modes were analyzed using polarized reflected light microscopy and scanning electron microscopy. Reliability was computed using Weibull analysis software (Reliasoft). RESULTS: The dominant failure mode for the over-pressed FDPs was buccal chipping of the porcelain in the loading area of the pontic, while hand veneered specimens failed mainly by combined failure modes in the veneering porcelain, framework, and abutments. Chipping of the porcelain occurred earlier in the over-pressed specimens (350 N/85 k, load/cycles) than in the hand-veneered ones (600 N/110 k) (profile I). Given a mission at 300 N load and 100 or 200 k cycles, the computed Weibull reliability (two-sided at 90% confidence bounds) was 0.99(1/0.98) and 0.99(1/0.98) for hand-veneered FDPs and 0.45(0.76/0.10) and 0.05(0.63/0) for over-pressed FDPs, respectively. CONCLUSIONS: In the range of average clinical loads (300-700 N), hand-veneered aluminum-oxide FDPs showed significantly less failure by chipping of the veneer than the over-pressed. Hand veneered FDPs under fatigue loading failed at loads >=600 N. PMID- 22093020 TI - Computer-aided pattern classification system for dermoscopy images. AB - BACKGROUND: Computer-aided pattern classification of melanoma and other pigmented skin lesions is one of the most important tasks for clinical diagnosis. To differentiate between benign and malignant lesions, the extraction of color, architectural order, symmetry of pattern and homogeneity (CASH) is a challenging task. METHODS: In this article, a novel pattern classification system (PCS) based on the clinical CASH rule is presented to classify among six classes of patterns. The PCS system consists of the following five steps: transformation to the CIE L*a*b* color space, pre-processing to enhance the tumor region and removal of hairs, tumor-area segmentation, color and texture feature extraction, and finally, classification based on a multiclass support vector machine. RESULTS: The PCS system is tested on a total of 180 dermoscopic images. To test the performance of the PCS diagnostic classifier, the area under the receiver operating characteristics curve (AUC) is utilized. The proposed classifier achieved a sensitivity of 91.64%, specificity of 94.14%, and AUC of 0.948. CONCLUSION: The experimental results demonstrate that the proposed pattern classifier is highly accurate and classify between benign and malignant lesions into some extend. The PCS method is fully automatic and can accurately detect different patterns from dermoscopy images using color and texture properties. Additional pattern features can be included to investigate the impact of pattern classification based on the CASH rule. PMID- 22093021 TI - Large-scale improvement initiatives in healthcare: a scan of the literature. AB - CONTEXT: The goal of this article is to provide a succinct scan of the literature as it relates to the current thinking and practice in large-scale improvement initiatives in healthcare. METHOD: We employed a scan of the literature using a modified Delphi technique. A standard review form was used. The scan was limited to large-scale spread efforts in hospitals and healthcare systems. Each of the main factors that emerged during the scan was linked to secondary factors and organized using a driver diagram. FINDINGS: Four primary drivers (factors) emerged during our scan that inform large-scale change initiatives in healthcare: Planning and Infrastructure; Individual, Group, Organizational, and System Factors; The Process of Change; and Performance Measures and Evaluation. CONCLUSION: Our scan identified a tremendous amount of work being done around the world to improve healthcare. In general, our findings suggest these initiatives tend to be fragmented from an implementation standpoint. We identified primary and secondary drivers (factors) that can be used by those responsible for implementing large-scale improvement initiatives both at a strategy level and in their daily work. These drivers could serve as a "checklist" of ideas to consider in different testing and implementation situations. PMID- 22093022 TI - Tooth loss in periodontally treated patients: a long-term study of periodontal disease and root caries. AB - AIM: To study periodontal conditions, root caries, number of lost teeth and causes for tooth loss during 11-14 years after active periodontal treatment. MATERIAL AND METHODS: Sixty-four patients participated in the follow-up study. Reasons for tooth loss were identified through previous case books, radiographs and clinical photos. To identify factors contributing to tooth loss, a logistic multilevel regression analysis was used. RESULTS: The number of lost teeth was 211. The main reason was periodontal disease (n = 153). Due to root caries and endodontic complications, 28 and 17 teeth, respectively, were lost. Thirteen teeth were lost for other reasons. The number of teeth (p = 0.05) and prevalence of probing pocket depths, 4-6 mm (p = 0.01) at baseline, smoking (p = 0.01) and the number of visits at dental hygienists (p = 0.03) during maintenance, significantly contributed to explain the variation in tooth loss. CONCLUSION: Previously treated patients at a specialist clinic for periodontology continued to lose teeth in spite of maintenance treatments at general practitioners and dental hygienists. The main reason for tooth loss was periodontal disease. Tooth loss was significantly more prevalent among smokers than non-smokers. Tooth related risk factors were smoking, low numbers of teeth and prevalence of periodontal pockets, 4-6 mm. PMID- 22093023 TI - Sample pooling obscures diversity patterns in intertidal ciliate community composition and structure. AB - The aim of this study was to assess the effect of sample pooling on the portrayal of ciliate community structure and composition in intertidal sediment samples. Molecular ciliate community profiles were obtained from nine biological replicates distributed in three discrete sampling plots and from samples that were pooled prior to RNA extraction using terminal restriction fragment polymorphism (T-RFLP) analyses of SSU rRNA. Comparing the individual replicates of one sampling plot with each other, we found a differential variability among the individual biological replicates. T-RFLP profiles of pooled samples displayed a significantly different community composition compared with the cumulative individual biological replicate samples. We conclude that sample pooling obscures diversity patterns in ciliate and possibly also other microbial eukaryote studies. However, differences between pooled samples and replicates were less pronounced when community structure was analyzed. We found that the most abundant T-RFLP peaks were generally shared between biological replicates and pooled samples. Assuming that the most abundant taxa in an ecosystem under study are also the ones driving ecosystem processes, sample pooling may still be effective for the analyses of ecological key players. PMID- 22093024 TI - Basal cell carcinoma, syringocystadenoma papilliferum, trichilemmoma, and sebaceoma arising within a nevus sebaceus associated with pigmented nevi. PMID- 22093025 TI - Mechanical stability of the femoral fixation for single- and double-bundle ACL reconstruction in an in vitro experimental model. AB - Anterior cruciate ligament ACL reconstruction using the double-bundle (DB) technique is gaining popularity. A possible weak link in the DB technique could be that two tendon grafts of smaller diameters are used. The purpose of this study was to test different femoral fixation methods and graft diameters representing single-bundle (SB) and DB ACL reconstructions and compare their biomechanical properties. We hypothesized that SB 6-mm graft constructs had inferior biomechanical properties than SB 9-mm grafts or DB 2 * 6-mm grafts. Furthermore, we hypothesized that interference (IF) screw fixation would demonstrate less elongation and a higher stiffness than Endobutton (Smith & Nephew(r), Inc., Andover, Massachusetts, USA) fixation (EBF). We performed an in vitro study using porcine knees and extensor tendons. The mechanical test consisted of a cyclic test followed by a load-to-failure test. We found that 6-mm graft constructs had an ultimate failure load that was up to 40% less than both the 9-mm and 2 * 6-mm graft constructs, despite the fixation method (P-values >= 0.004). Comparing fixation methods, EBF was superior to IF concerning maximum load to failure (P < 0.001); IF resulted in a higher stiffness of the femur/graft complex than the EBF (P < 0.001) but no significant difference in elongation between fixation methods. Since the two graft strands are subjected to different loads in different knee flexion angles, the reduced strength of the individual graft strands in DB ACL reconstruction could be a concern. PMID- 22093026 TI - A single-center study of hematopoietic stem cell transplantation for primary immune deficiencies (PIDD). AB - PIDD are rare inherited disorders that can result in life-threatening infections. Allogeneic HSCT is the only cure for many primary immune deficiencies; however, the specific diseases and optimal type(s) of transplants are not clear. This study compares transplant outcomes in a large cohort with a relatively uniform pre- and post-transplant management strategies. We conducted a retrospective analysis of 39 pediatric patients who underwent HSCT for SCID (n = 25) or other immune deficiencies (n = 14) from 1986 to 2010. A structured case report form was used to collect clinical information. The outcomes of survival, immune reconstitution, engraftment, incidence of GvHD and IVIG dependency were tabulated. Overall survival rates were 88% for SCID and 86% for other primary immune deficiencies, which are high compared to other historical series. No single variable was associated with mortality. Immunoglobulin dependence occurred only in patients who had X-linked SCID and a parental donor haploidentical transplant. Because of improved supportive care and use of alternative donors and conditioning regimens, HSCT has become an acceptable option for an increasing number of PIDD subtypes not previously transplanted with high frequency. This study encourages greater use of transplantation. PMID- 22093027 TI - A novel fingerprint method to assess the diversity of methanogens in microbial systems. AB - Understanding the ecology of methanogens in natural and engineered environments is a prerequisite to predicting or managing methane emissions. In this study, a novel high-throughput fingerprint method was developed for determining methanogen diversity and relative abundance within environmental samples. The method described here, designated amplicon length heterogeneity PCR of the mcrA gene (LH mcrA), is based on the natural length variation in the mcrA gene. The mcrA gene encodes the alpha-subunit of the methyl-coenzyme M reductase, which is involved in the terminal step of methane production by methanogens. The methanogenic communities from stored swine and dairy manures were distinct from each other. To validate the method, methanogenic communities in a plug flow-type bioreactor (PFBR) treating swine manure were characterized using LH-mcrA method and correlated to mcrA gene clone libraries. The diversity and relative abundance of the methanogenic groups were assessed. Methanobrevibacter, Methanosarcinaceae, Methanoculleus, Methanogenium, Methanocorpusculum and one unidentified group were assigned to particular LH-mcrA amplicons. Particular phylotypes related to Methanoculleus were predominant in the last compartment of the PFBR where the bulk of methane was produced. LH-mcrA method was found to be a reliable, fast and cost-effective alternative for diversity assessment of methanogenic communities in microbial systems. PMID- 22093028 TI - Effect of prednisone administration on coagulation variables in healthy Beagle dogs. AB - BACKGROUND: Long-term corticosteroid therapy has been associated with increased risk of thrombotic disease in dogs. OBJECTIVE: The purpose of this prospective study was to use thrombelastography (TEG) and thrombin generation (TG) to detect development of a hypercoagulable state in healthy Beagle dogs receiving oral prednisone. We hypothesized that administration of corticosteroids would result in a hypercoagulable profile on TEG tracings and an increase in TG. METHODS: Six healthy adult Beagles from the University of Montreal's research colony were used to conduct a prospective longitudinal study in which all dogs received 1 mg/kg of prednisone orally once daily for 2 weeks, followed by a 6-week washout period, and then 4 mg/kg of prednisone orally once daily for 2 weeks. TEG tracings on citrated whole blood and TG measurements on frozen-thawed platelet-poor plasma were obtained before prednisone administration (baseline), at the end of the washout period, and at the end of both corticosteroid trials. RESULTS: Significant differences compared with baseline values were obtained for K, alpha, and MA, with tracings compatible with a hypercoagulable profile following both corticosteroid trials. There was a significant increase in endogenous thrombin potential only after low-dose (1 mg/kg) prednisone. CONCLUSION: Administration of prednisone to healthy Beagles resulted in hypercoagulability as indicated by TEG tracings, whereas the effect on TG was more variable. Further studies are needed to determine the underlying mechanisms of hypercoagulability and its clinical impact. PMID- 22093029 TI - The effect of hydrophilic titanium surface modification on macrophage inflammatory cytokine gene expression. AB - OBJECTIVES: Chemical modification of microrough titanium dental implants to produce a hydrophilic surface with increased wettability and improved surface energy has been demonstrated clinically to achieve superior bone wound healing and osseointegration compared to that achieved with a microrough titanium surface alone. As the recruitment of the necessary osseoinductive precursors involved in bone wound healing and osseointegration to the wound site is facilitated by the action of cytokines, this study sought to determine the in vitro effect of hydrophilic surface modification on the expression of pro-inflammatory cytokines from adherent macrophages. MATERIAL AND METHODS: The surface topography and composition of the titanium surfaces was characterized by scanning electron microscopy and X-ray photoelectron spectroscopy. Macrophage attachment and proliferation was assessed using an MTT assay. The expression of 84 pro inflammatory cytokines and chemokines by adherent RAW 264.7 cells, a murine leukaemic monocyte cell line, was assessed by PCR array after 24 h culture on either smooth polished, sand-blasted acid-etched (SLA) or hydrophilic-modified SLA (SLActive) titanium surfaces. RESULTS: Following 24 h culture on titanium, surface microroughness activated pro-inflammatory cytokine gene transcription in RAW 264.7 cells. Although there was no significant difference in the degree of cellular attachment or proliferation of RAW 264.7 cells to the different titanium surfaces, by 24 h the hydrophilic surface elicited a gene expression profile with significant down-regulation of the key pro-inflammatory cytokines Tnfalpha, IL 1alpha, IL-1beta and the chemokine Ccl-2. CONCLUSIONS: Down-regulation of the expression of pro-inflammatory cytokine genes may thus modulate the inflammatory response and may facilitate the enhanced bone wound healing and osseointegration observed clinically using implants with a microrough hydrophilic surface. PMID- 22093030 TI - Earlobe keloids: classification according to gross morphology determines proper surgical approach. AB - BACKGROUND: A previous study described the outcomes of a treatment protocol using a prospective design and identified three clinical risk factors for recurrent keloids. OBJECTIVE: To introduce a novel classification of earlobe keloids through a retrospective study and describe the appropriate surgical methods according to this new classification. METHODS: One thousand twenty-seven earlobe keloids were treated at Kangbuk Samsung Hospital from March 2001 to February 2011. All cases were studied retrospectively and classified. RESULTS: The earlobe keloids were classified into five groups. The frequency of earlobe keloids in descending order were a sessile type, single nodular pattern; pedunculated type; sessile type, multinodular pattern; buried type; and mixed type. Different surgical methods were used based on the Chang-Park classification according to gross morphology, including core extirpation using a penetrating technique, standard keloidectomy, radical keloidectomy, keloidectomy with core extirpation, and a combination of these. All cases were closed primarily without skin grafting or sacrifice of the surrounding tissue. CONCLUSIONS: This novel classification for earlobe keloids can lead to a better understanding of the different types of earlobe keloids and inform decisions regarding surgical methods. PMID- 22093031 TI - Virus-triggered autophagy in viral hepatitis - possible novel strategies for drug development. AB - Autophagy is a very tightly regulated process that is important in many cellular processes including development, differentiation, survival and homoeostasis. The importance of this process has already been proven in numerous common diseases such as cancer and neurodegenerative disorders. Emerging data indicate that autophagy plays an important role in some liver diseases including liver injury induced by ischaemia reperfusion and alpha-1 antitrypsin Z allele-dependent liver disease. Autophagy may also occur in viral infection, and it may play a crucial role in antimicrobial host defence against pathogens, while supporting cellular homoeostasis processes. Here, the latest findings on the role of autophagy in viral hepatitis B and C infection, which are both serious health threats, will be reviewed. PMID- 22093032 TI - Chronic hepatitis C infection blocks the ability of dendritic cells to secrete IFN-alpha and stimulate T-cell proliferation. AB - Dendritic cells (DCs) are likely to play a key role in the compromised T-cell function associated with hepatitis C Virus (HCV) infection. However, studies of DC function in HCV-infected patients to date have yielded conflicting findings possibly because of patient and virus heterogeneity. Here, we report the characterization of monocyte-derived DCs obtained from a homogenous cohort of women who were infected with HCV genotype 1b following exposure to contaminated anti-D immunoglobulin from a single donor source. Patients included in the study had not received anti-viral therapy and all had mild liver disease. We show that phenotypically normal monocyte-derived dendritic cells (MDDCs) (CD11c(+) HLA(-) DR(+) CD1a(+) CD14(lo) ) can be obtained from these patients. These cells respond to both Poly(I:C) and LPS, by up-regulating expression of CD86. They secrete high levels of IL-8 and CCL5 in response to LPS, an indication that the MyD88 dependent and MyD88-independent signalling pathways downstream of TLR4 ligation are functioning normally. However, these cells are poor stimulators of T-cell proliferation in allogeneic mixed lymphocyte reactions. Furthermore, patient MDDCs fail to secrete IFN-alpha in response to poly(I:C) or IFN-beta stimulation. Altered DC function may contribute to impaired cellular immune responses and chronicity of disease following HCV infection in this cohort. An effective therapeutic vaccine for chronic HCV infection will most likely need to target DCs to elicit an appropriate cellular response; therefore, it is important to resolve how the DCs of different patient cohorts respond to stimulation via TLRs. PMID- 22093033 TI - Hepatitis C virus and the immunological response to hepatitis B virus vaccine in dialysis patients: meta-analysis of clinical studies. AB - It is well known that the seroconversion rate of patients following hepatitis B virus (HBV) vaccination is lower in uraemic than healthy subjects. A variety of inherited or acquired factors have been implicated in this diminished response, and the high prevalence of hepatitis C virus (HCV) infection among patients on maintenance dialysis has been suggested to play a role. However, the impact of HCV on the immune response to HB vaccine in patients receiving long-term dialysis is not entirely understood. Here, we evaluate the influence of HCV infection on the immunological response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies.We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titres at completion of HBV vaccine schedule among HCV-positive versus HCV-negative patients on chronic dialysis. We identified eight studies involving 520 unique patients on long-term dialysis. Aggregation of study results did not show a significant decrease in response rates among HCV-infected versus noninfected patients [pooled odds ratio = 0.621 (95% CI, 0.285; 1.353)]. The P-value was 0.007 for our test of study heterogeneity. Stratified analysis in various subgroups of interest did not meaningfully change our results. Our meta-analysis showed no association between immunological response to hepatitis B vaccine and HCV infection in individuals on long-term dialysis. These results support the use of recombinant vaccine against hepatitis B in patients on regular dialysis with HCV infection. PMID- 22093034 TI - Clinical features and risk factors of creatine kinase elevations and myopathy associated with telbivudine. AB - With the extensive use of telbivudine, more and more studies reported its association with creatine kinase (CK) elevations and myopathy. However, clinical features of these adverse effects were poorly understood. The aim of the present study was to investigate the clinical features and risk factors of CK elevations and myopathy associated with telbivudine. The serum CK levels of 200 patients who were treated with telbivudine for chronic hepatitis B (CHB) between January 2007 and July 2010 were monitored and analysed along with clinical manifestations. The 3-year cumulative incidence of CK elevations and myopathy was 84.3% and 5%, respectively. CK elevations occurred more frequently in men than in women, and patients aged <=45 years and with negative HBeAg had higher incidence of CK elevations. There was no difference in CK elevations among patients with different HBV DNA levels. Male, younger age and HBeAg negativity were independent predictors of CK elevations by multivariate Cox regression analysis. There was no association between the occurrence of myopathy and variables including age, sex, HBeAg and HBV DNA. No risk factors of myopathy were identified. CK elevations usually occurred 21 months after starting treatment, and most patients resolved spontaneously without interruption of telbivudine therapy except three patients who had to switch to other agents. In conclusion, CK elevations are common adverse reactions associated with telbivudine therapy, while myopathy is rare. Male, younger age and HBeAg negativity might be risk factors of CK elevations. PMID- 22093035 TI - Effect of dietary citric acid on the performance and mineral metabolism of broiler. AB - The objective of this study was to investigate the effect of dietary citric acid (CA) on the performance and mineral metabolism of broiler chicks. A total of 1720 Ross PM3 broiler chicks (days old) were randomly assigned to four groups (430 in each) and reared for a period of 35 days. The diets of groups 1, 2, 3 and 4 were supplemented with 0%, 0.25%, 0.75% or 1.25% CA by weight respectively. Feed and faeces samples were collected weekly and analysed for acid insoluble ash, calcium (Ca), phosphorus (P) and magnesium (Mg). The pH was measured in feed and faeces. At the age of 28 days, 10 birds from each group were slaughtered; tibiae were collected from each bird for the determination of bone mineral density, total ash, Ca, P, Mg and bone-breaking strength, and blood was collected for the measurement of osteocalcin, serum CrossLaps((r)), Ca, P, Mg and 1,25(OH)(2)Vit-D in serum. After finishing the trial on day 37, all chicks were slaughtered by using the approved procedure. Birds that were fed CA diets were heavier (average body weights of 2030, 2079 and 2086 g in the 0.25%, 0.75% and 1.25% CA groups, respectively, relative to the control birds (1986 g). Feed conversion efficiency (weight gain in g per kg of feed intake) was also higher in birds of the CA-fed groups (582, 595 and 587 g/kg feed intake for 0.25%, 0.75% and 1.25% CA respectively), relative to the control birds (565 g/kg feed intake). The digestibility of Ca, P and Mg increased in the CA-fed groups, especially for the diets supplemented with 0.25% and 0.75% CA. Support for finding was also indicated in the results of the analysis of the tibia. At slaughter, the birds had higher carcass weights and higher graded carcasses in the groups that were fed the CA diets. The estimated profit margin was highest for birds fed the diet containing 0.25% CA. Birds of the 0.75% CA group were found to have the second highest estimated profit margin. Addition of CA up to a level of 1.25% of the diet increased performance, feed conversion efficiency, carcass weight and carcass quality, but only in numerical terms. The addition of CA up to 0.75% significantly increased the digestibility of macro minerals, bone ash content, bone mineral density and bone strength of the broiler chicks. It may, therefore, be concluded that the addition of 0.75% CA in a standard diet is suitable for growth, carcass traits, macromineral digestibility and bone mineral density of broiler chicks. PMID- 22093036 TI - Successful treatment of cosmetic mucosal tattoos via Q-switched laser. AB - BACKGROUND: Tattoo removal using Q-switched lasers is well established in the medical literature, but it is not clear how tattoos on mucosal membranes should be treated because of their infrequent presentation. OBJECTIVE: To report successful cosmetic tattoo removal using Q-switched laser irradiation on the oral mucosal surface. MATERIALS AND METHODS: Three men with cosmetic tattoos on the orolabial mucosa of the lower lip sought permanent removal. Each patient received treatments using a Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser to the desired endpoint. RESULTS: Treatment of the affected area with the Nd:YAG laser resulted in clearing of the pigment without scarring. CONCLUSION: Q switched laser treatment is a safe and very effective means of removing cosmetic mucosal tattoos on the inner lip and should be considered the criterion standard treatment option. PMID- 22093038 TI - Development of new strains and related SCAR markers for an edible mushroom, Hypsizygus marmoreus. AB - New fast-growing and less bitter varieties of Hypsizygus marmoreus were developed by crossing monokaryotic mycelia from a commercial strain (Hm1-1) and a wild strain (Hm3-10). Six of the better tasting new strains with a shorter cultivation period were selected from 400 crosses in a large-scale cultivation experiment. We attempted to develop sequence characterized amplified region (SCAR) markers to identify the new strain from other commercial strains. For the SCAR markers, we conducted molecular genetic analysis on a wild strain and the eight most cultivated H. marmoreus strains collected from various areas in East Asia by randomly amplified polymorphic DNA. Ten unique DNA bands for a commercial Hm1-1 strain and the Hm3-10 strain were extracted and their sequences were determined. Primer sets were designed based on the determined sequences. PCR reactions with the primer sets revealed that four primer sets successfully discriminated the new strains from other commercial strains and are thus suitable for commercial purposes. PMID- 22093037 TI - Microbial diversity in bovine papillomatous digital dermatitis in Holstein dairy cows from upstate New York. AB - Papillomatous digital dermatitis (PDD) is one of the most prevalent diseases of cattle, adversely affecting the dairy industry by its negative effect on milk production and reproductive performance. Our objective was to use culture independent methods to determine the microbial diversity in different strata of PDD lesions of three Holstein dairy cows, analyzing whether major differences exist compared to foot skin of three non-infected cows. Both group-specific 16S rRNA gene PCR-denaturing gradient gel electrophoresis and clone library sequencing of broad-range 16S rRNA gene showed differences between the microbial composition of healthy dairy cows and the different strata of the lesion. The predominant bacterial community in the lesion, regardless of the stratum, consisted of 166 specific phylotypes belonging to seven bacterial phyla. Spirochetes (particularly, treponemes) was the most prominent group detected in PDD deep biopsies and was only found in samples from the lesion. Additionally, one phylotype phylogenetically affiliated with uncultured Euryarchaeota was detected in two strata of the lesion. Sequences from healthy foot skin samples revealed 86 specific phylotypes that were affiliated with Firmicutes and Proteobacteria. Our study corroborates the theory that treponemes are involved in PDD disease etiology and suggests, for the first time, the presence of archaeal members in this particular bovine infection. PMID- 22093039 TI - Evaluation of the safety and efficiency of novel metallic ultrasonic scaler tip on titanium surfaces. AB - AIM: To evaluate the safety and efficiency of novel ultrasonic scaler tips, conventional stainless-steel tips, and plastic tips on titanium surfaces. MATERIAL AND METHODS: Mechanical instrumentation was carried out using conventional ultrasonic scalers (EMS, Nyon, Switzerland) with novel metallic implant tip (BS), a plastic-headed tip (ES), a plastic tip (PS) and a conventional stainless-steel tip (CS) on 10 polished commercially pure titanium disks (Grade II) per group. Arithmetic mean roughness (R(a) ) and maximum height roughness (R(y) ) of titanium samples were measured and dissipated power of the scaler tip in the tip-surface junction was estimated to investigate the scaling efficiency. The instrumented surface morphology of samples was viewed with a scanning electron microscope (SEM) and surface profile of the each sample was investigated using contact mode with a commercial atomic force microscope (AFM). RESULTS: There were no significant differences in surface roughness (R(a) and R(y) ) among BS, ES, and PS group. However, CS group showed significant higher surface roughness (R(a) and R(y) ). The efficiency of CS tip is twice as much higher than that of BS tip, the efficiency of BS tip is 20 times higher than that of PS tip, and the efficiency of BS tip is 90 times higher than that of ES tip. CONCLUSION: Novel metallic copper alloy ultrasonic scaler tips may minimally influence the titanium surface, similar to plastic tip. Therefore, they can be a suitable instrument for implant maintenance therapy. PMID- 22093040 TI - Methods for evaluation of cosmetic antioxidant capacity. AB - The skin as the largest part of human body is one of the main targets for ultraviolet radiation, environmental pollution, toxic chemicals and some metal ions, which share responsibility for the formation of free radicals. The resulting free radicals, both oxygen and nitrogen species are one of the main causes of aging due to impaired regulation of cell respiratory metabolism involving incomplete oxygen reduction in mitochondria and production a superoxide anion, hydroxyl radicals et al. In modern cosmetology to minimize the adverse effects of free radicals, antioxidants, which inhibit free radical reactions, mainly autoxidation processes are used. Currently, not only many cosmetic products containing antioxidants are available, but a large diversity of methods for determination of cosmetics antioxidant activity is also accessible. These methods can be divided into three main groups: in vitro, in vivo, and ex vivo as reported herein. Due to lack of standardization and validation it is necessary to use a variety of methods as well as conditions for those purposes, which are presented to the context. PMID- 22093041 TI - Evaluation of the child with atopic dermatitis. AB - Atopic dermatis (AD) is a very common inflammatory skin disease in childhood. Various doctors such as paediatricians, general practitioners, allergologists and dermatologists are regularly consulted by these children and their parents, but there is no clear consensus on the diagnostic work-up that should be performed when evaluating a child with eczema. A careful history, clinical examination and adequate documentation of disease severity are essential in all children with eczema, irrespective of their disease severity. AD is a clinical diagnosis; diagnostic criteria, such as the UK diagnostic criteria, can be helpful for an accurate definition of the disease. A careful history, including alarm symptoms, respiratory symptoms and the impact of the disease on psychosocial functioning is important. Clinical scoring lists such as SCORAD and EASI are well validated for clinical studies; they are, however, not very suitable tools in clinical practice. More simple scoring systems, such as Three Item Severity Score (TIS) and Investigator Global Assessment (IGA), are more easy to use for clinical record keeping in daily practice. Allergen testing in children with AD without a history of acute non-eczematous reactions after allergen exposure is not necessary. In very young children with eczema, not yet exposed to foods, routine allergen testing is not necessary. If in individual cases, the decision is made to perform allergen tests, oral challenges should performed to confirm the diagnoses of food allergy. PMID- 22093042 TI - The proteome and gene expression profile of cementoblastic cells treated by bone morphogenetic protein-7 in vitro. AB - AIM: Regenerative periodontal therapy is often unpredictable and limited. Cementum regeneration is necessary for the proper repair of a periodontal ligament. The precise mechanism how bone morphogenetic protein-7 (BMP7) induces differentiation and mineralization of cementoblasts remains undetermined. The purpose of this study was to evaluate the effect of BMP7 on early proteome and gene expression profile of cementoblastic OCCM.30 cells in vitro. MATERIALS AND METHODS: Immortalized murine cementoblasts (OCCM.30) were exposed to BMP7 and evaluated for: (1) proliferation; (2) mineralization; (3) early proteome profile using liquid chromatography-mass spectrometry (LC-MS); and (4) gene expression by quantitative RT-PCR. RESULTS: Bone morphogenetic protein-7 increased the cell proliferation at 24 h and 48 h, while higher doses suppressed the cell proliferation at 48 h. BMP7 induced the mineralization of cementoblasts following 8 days of therapy. Using LC-MS we identified 1117 proteins from the cell lysate. Many belonged to extracellular matrix formation such as PCPE1, collagens, annexins and integrin receptors. RT-PCR analyses revealed a BMP7 dose-dependent upregulation of BMP1, TGFbeta1, osterix, osteoprotegerin, procollagen I and II, PCPE1, and noggin, while BMP6 and chordin expression were decreased. The high BMP7 dose down regulated most of the genes 24 h following therapy. CONCLUSION: Bone morphogenetic protein-7 promotes differentiation and mineralization of cementoblasts via inducing PCPE1 and BMP1 responsible for processing of type I collagen. PMID- 22093043 TI - Use of the Internet as a source of health information amongst participants of antenatal classes. AB - AIM: To describe the pattern of use of the Internet as a source of health information by participants of antenatal classes. Background. There is a lack of information about the frequency of Internet use amongst expectant mothers and fathers who attend antenatal classes. DESIGN: A cross-sectional descriptive study. METHODS: Women (n = 114) and men (n = 21) were recruited. Data were collected anonymously using a self-administered questionnaire, containing questions about Internet use, the frequency of that use, sources of information about pregnancy, preference over other non-Internet sources, positive and negative feelings generated due to the use of the Internet and willingness to receive instructions on Internet use. RESULTS: The average age of participants was 31.4 (SD 6.1) and their stage of pregnancy ranged from 24-38 weeks. 83.5% were expecting their first child. 93.5% reported that they used the Internet on a regular basis and no significant difference was found between men and women. Amongst Internet users, 97.7% sought, at some point, information on pregnancy on the Internet and 26.9% had done so in the last 24 hours. The Internet was the most popular source of information on pregnancy topics (18.5% of women and 25.8% of men used it as their primary source of information) after a physician. Commercial websites were more frequently used by people looking for information on pregnancy than sites maintained by not-for-profit organisations or professional unions. CONCLUSIONS: The Internet is widely used as a source of information amongst participants of antenatal classes, both male and female. Approximately 95% have used it at some point to find information during pregnancy, but the majority (approximately 90%) had no knowledge of websites run by not-for-profit organisations and preferred commercial websites. Relevance to clinical practice. Instead of disregarding the use of the Internet as a source of information during pregnancy, midwives should keep up to date and give their patients links to high-quality sites. PMID- 22093044 TI - Rhinitis symptoms caused by grass pollen are associated with elevated basophile allergen sensitivity and a larger grass-specific immunoglobulin E fraction. AB - BACKGROUND: The mechanisms responsible for the difference between clinically irrelevant IgE-sensitization and allergic rhinitis are not fully understood. OBJECTIVE: We evaluated the humoral and cellular mechanisms that may be associated with the presence of allergic rhinitis symptoms. METHODS: We selected 26 subjects with positive grass pollen skin tests and IgE antibodies to Timothy (g6) and the major grass allergens rPhl p 1, 5b. Fourteen of those patients reported a history of allergic rhinitis. During winter, we performed a grass pollen CD63 basophile activation test using four log allergen concentrations, followed by a grass nasal provocation test (NPT). We obtained symptom scores in the subsequent pollination season. RESULTS: We showed that subjects with a positive NPT have significantly higher CD63 basophile grass pollen responsiveness than NPT-negative subjects, preferably at submaximal allergen concentrations, which represent cellular sensitivity. Moreover, basophile sensitivity positively correlated with the size of the grass-specific IgE fraction in relation to total IgE, and it was highly predictive of allergic rhinitis symptoms in the following pollination season. CONCLUSION AND CLINICAL RELEVANCE: Allergic rhinitis symptoms are significantly associated with allergen-specific basophile sensitivity. In vitro evaluation of basophile sensitivity should prove useful for distinguishing clinical phenotype of allergic sensitization. PMID- 22093045 TI - Staphylococcal enterotoxin B compromises the immune tolerant status in the airway mucosa. AB - BACKGROUND: The breakdown of immune tolerance plays a critical role in allergic disorders; the mechanism of breaching immune tolerance remains largely unknown. OBJECTIVE: The present study aimed to investigate the role of Staphylococcal enterotoxin B (SEB) in the interference of the immune tolerance in the nasal mucosa. METHODS: The immune tolerant components, tolerogenic dendritic cells (TolDC) and regulatory T cells (Treg), were assessed in the surgically removed nasal mucosa from patients with allergic rhinitis (AR) or non-AR chronic rhinitis. The contents of SEB and integrin alphavbeta6 (avb6) in the nasal epithelium were assessed using enzyme-linked immunoassay. The ability of avb6 on TolDC induction and the effect of SEB on suppression of avb6 in nasal epithelial cells were observed in cell culture. RESULTS: Compared with that in the non-AR nasal mucosa, the frequencies of TolDCs/Tregs were lower, the contents of SEB were higher and the contents of avb6 were lower in the AR nasal mucosa. Avb6 had the ability to induce the development of TolDCs in vitro; the latter had the ability to induce Treg development. The expression of avb6 was detected in nasal epithelial cells in culture that could be suppressed by SEB. CONCLUSIONS AND CLINICAL RELEVANCE: The components of immune tolerance machinery, TolDCs and Tregs were suppressed in the AR nasal mucosa. The increases in SEB and decreases in avb6 in nasal epithelium are associated with the compromises of immune tolerance in the nasal mucosa. SEB has the ability to suppress the expression of avb6 in nasal epithelial cells. PMID- 22093046 TI - Yellow fever vaccination in organ transplanted patients: is it safe? A multicenter study. AB - BACKGROUND: Yellow fever (YF) may be very serious, with mortality reaching 50%. Live attenuated virus YF vaccine (YFV) is effective, but may present, although rare, life-threatening side effects and is contraindicated in immunocompromised patients. However, some transplant patients may inadvertently receive the vaccine. METHODS: A questionnaire was sent to all associated doctors to the Brazilian Organ Transplantation Association through its website, calling for reports of organ transplanted patients who have been vaccinated against YF. RESULTS: Twelve doctors reported 19 cases. None had important side effects. Only one had slight reaction at the site of YFV injection. Eleven patients were male. Organs received were 14 kidneys, 3 hearts, and 2 livers. Twelve patients received organs from deceased donors. Mean age at YFV was 45.6 +/- 13.6 years old (range 11-69); creatinine: 1.46 +/- 0.62 mg/dL (range 0.8-3.4); post-transplant time: 65 +/- 83.9 months (range 3-340); and time from YFV at the time of survey: 45 +/- 51 months (range 3-241). Immunosuppression varied widely with different drug combinations: azathioprine (7 patients), cyclosporine (8), deflazacort (1), mycophenolate (10), prednisone (11), sirolimus (3), and tacrolimus (4). CONCLUSIONS: YFV showed no important side effects in this cohort of solid organ transplanted patients. However, owing to the small number of studied patients, it is not possible to extend these findings to the rest of the transplanted population, assuring safety. Therefore, these data are not strong enough to safely recommend YFV in organ transplanted recipients, as severe, even life threatening side effects may occur. PMID- 22093047 TI - Clinical and radiographic evaluation of early loaded narrow diameter implants - 1 year follow-up. AB - OBJECTIVE: To evaluate the clinical performance of Astra Tech OsseoSpeed TX 3.0S implants using one-stage surgical procedure and early loading in the anterior region. MATERIAL AND METHODS: This is a prospective, single arm, multi-centre study. Patients missing teeth at positions 12, 22 and 32-42 were eligible to enter the study. The implants (OsseoSpeed TX 3.0S) used in the study were of 3 mm diameter and of different lengths. One-stage surgery was performed, and healing abutments were used during the 6-10 weeks healing period. Clinical and radiographic examinations were assessed at implant installation, loading and at the 6- and 12-month follow-up visits. RESULTS: Ninety-seven implants were placed in 69 patients at six different study centres in Denmark, Germany, Italy, Spain, Sweden and the United Kingdom. The survival rate was 95.9%. No implants have been lost after loading (100% survival rate after loading). Mean marginal bone loss 1 year after installation was 0.065 mm (SD = 1.018). The frequency of bone loss >= 1 mm was 6.6% and 51.3% of the implants demonstrated no bone loss or even bone gain from the surgical visit to the first year follow-up visit. Mean probing pocket depth and gingival zenith score were stable from crown placement to the 6- and 1-year follow-up visits. CONCLUSION: Treatment with OsseoSpeed TX 3.0S implants is a safe and predictable option in the anterior region where physical space is limited. Minimal marginal bone loss was observed during the first year follow-up. PMID- 22093048 TI - Determination of the protection efficacy and homogeneity of the distribution of sunscreens applied onto skin pre-treated with cosmetic products. AB - BACKGROUND: The efficacy of sunscreens depends decisively on the homogeneity of its distribution on the skin surface, which is sensitively reflected by two spectroscopic data - the factor of inhomogeneity and the sum transmission - measured after tape stripping. The aim of this study was to investigate the influence of a skin pre-treatment with body lotion on the layout of the formulations. METHODS: Six healthy volunteers were pre-treated using the body lotion, Nivea Body (Beiersdorf AG, Hamburg, Germany). The sunscreen was an oil/water (o/w) emulsion, Roc SPF 8 (RoC SA, Paris, France). The tape stripped tesa films were measured with a modified UV/VIS spectrometer Lambda 5 (PerkinElmer, Frankfurt/Main, Germany), the data of which were used to calculate both measurands. RESULTS: The obtained results made clear that the original spectroscopic data must be corrected taking into account the changed amounts of horny layer particles removed with the individual tape strips after pre treatment. As a consequence of the correction, the factors of inhomogeneity as well as the sum transmissions confirm a more homogeneous distribution of the applied sunscreen. CONCLUSION: The findings confirm that the applied method is well suited to obtain information on the distribution of topically applied substances, and furthermore that the influence of the pre-treatment of the skin with the body lotion enhances the homogeneity of distribution and thus the sunscreen efficacy. PMID- 22093049 TI - Timing of rectosigmoid resection for diverticular disease: the patient's view. AB - AIM: The study aimed to determine the patient's view on the timing of elective resection for sigmoid diverticulitis. METHOD: A questionnaire was answered by 162 (69%) of 236 consecutive patients who had a resection of the rectosigmoid for diverticulitis from July 2002 to August 2005. Patients (n=45) having resection at or after the first inflammatory attack were excluded, leaving 117 eligible for analysis. Questions asked included those concerning symptoms before surgery, improvement of symptoms after surgery and the timing of surgery. RESULTS: Patient assessment of symptoms after surgery was as follows: no improvement (2%; n=2), some improvement (10%; n=12), marked improvement (34%; n=39) and complete resolution (54%; n=63). Forty-five (38%) patients would have preferred an earlier operation. Preference for earlier surgery related to the number of previous inflammatory attacks was expressed as follows: 13 (34%) of 38 patients after two inflammatory attacks, 5 (18%) of 28 patients after three, seven (37%) of 19 patients after four, four (44%) of nine patients after five, and 16 (70%) of 23 patients after six or more inflammatory attacks would have preferred earlier surgery. Statistically significant factors influencing this potential choice were number of episodes of pain (P=0.006, OR=1.23, 95% CI: 1.060-1.430) and number of attacks of inflammation (P=0.048, OR=1.27, 95% CI: 1.002-1.598). CONCLUSION: Surgery for recurrent diverticulitis resulted in a marked improvement or complete relief of symptoms in 88% of patients. A large proportion of patients with recurrent episodes of sigmoid diverticulitis would have preferred earlier resection. PMID- 22093050 TI - Continuity of care between family practice physicians and hospitalist services. AB - PURPOSE: Hospitalist services are increasing in popularity and fewer primary care providers (PCPs) are caring for patients while hospitalized. Due to concerns with discontinuity of care, this study evaluated communication and medication discrepancies on admission and discharge between PCPs without admitting privileges and hospitalist physicians. METHODS: This retrospective analysis evaluated patients from a PCP office admitted to hospitalist services from January 2009 through July 2009. Patient charts were evaluated for PCP, age, gender, insurance, modes and timeliness of PCP notification, medications on admission and discharge, and medication discrepancies. RESULTS: A total of 120 charts were evaluated. Physicians were contacted by receipt of admission summaries for 93% of patients and by phone for 5.8% of patients. Twenty-one percent of admission summaries were received by the PCP after the patient was discharged from the hospital and 7% of discharge summaries were received after the first hospital follow-up with the PCP. Medication errors occurred frequently and the rate increased in patients at least 65 years old, if they had Medicare, Medicaid, or were without insurance coverage. CONCLUSION: Better communication and documentation of medication regimens are needed to improve continuity of care of patients between outpatient and inpatient settings and avoid potentially harmful medication errors. PMID- 22093051 TI - Tissue integration of collagen-based matrices: an experimental study in mice. AB - OBJECTIVES: To test whether or not tissue integration, biodegradation, and new blood vessel formation in two collagen-based matrices depend on the level of chemical cross-linking. MATERIAL AND METHODS: Two collagen matrices with high (CM1) and low (CM2) levels of chemical cross-linking were randomly implanted in two pouches in 14 athymic nude mice. Three and 6 weeks later, the animals were euthanized. Histologic and histomorphometric measurements were performed on paraffin-embedded sections. RESULTS: Both collagen matrices integrated well into the surrounding soft tissues. The level of cross-linking and duration of implantation had an effect on the formation of new blood vessels. More blood vessels (n = in absolute numbers) were found in outer compartments compared to the central compartments of the matrices, reaching 5.6 (CM2) vs. 4.3 (CM1) at 3 weeks, and 5.3 (CM2) vs. 7.3 (CM1) at 6 weeks. Similarly, connective tissue formation increased for both matrices between 3 and 6 weeks, whereas the amount of remaining collagen network gradually decreased over time being more pronounced for CM1 (-50%) compared to CM2 (-15%). CONCLUSIONS: The degree of cross-linking was negatively correlated for all outcome measures resulting in improved tissue integration, superior matrix stability and enhanced angiogenic patterns for the less cross-linked collagen matrix (CM2) in this experimental study in mice. PMID- 22093052 TI - Defining a periodontitis case: analysis of a never-treated adult population. AB - AIM: The purpose of the present study was to assess the extent to which the three periodontitis case definition systems proposed by van der Velden, Tonetti & Claffey and Page & Eke identify the same cases in a population of never-treated adults with limited tradition for oral hygiene procedures. MATERIAL AND METHODS: Based on data on clinical attachment level (CAL), probing pocket depth (PD) and bleeding on probing (BOP) of four sites in all teeth present among 1,130 adult Kenyans we classified the population according to the three case definition systems, and according to the occurrence of the concomitant presence of CAL and BOP at the site level. RESULTS: The case definitions by Tonetti & Claffey and by Page & Eke yielded similar results, which were also quite similar to the results of simply identifying a case of periodontitis as a person having at least one site showing both CAL >= 4 mm and BOP. CONCLUSIONS: The results indicate that it should be feasible for the periodontal community to reach an agreement over the distinction between a case and a non-case. The classification system proposed by van der Velden is better suited for providing clinicians with a clear image of the case. PMID- 22093053 TI - Topical timolol for a refractory wound. PMID- 22093054 TI - Combined treatment with a nonablative infrared device and hyaluronic acid filler does not have enhanced efficacy in treating nasolabial fold wrinkles. AB - BACKGROUND: Although hyaluronic acid (HA) fillers are extensively used for the correction of facial wrinkles and folds, there is a limit to patient satisfaction, especially in patients with severe wrinkles. OBJECTIVE: To evaluate the potential for synergistic effects with combined treatment using a nonablative infrared (IR) device and HA filler in the treatment of nasolabial fold (NLF) wrinkles. MATERIALS AND METHODS: This was a split-face randomized study in which 12 Korean patients were treated with HA filler on both NLFs and with a nonablative IR device on the experimental side of the face. Clinical evaluations from subjects and investigators and photographs were obtained at baseline, just before and after the procedures, and 1 and 2 months after completion of the procedures. RESULTS: There were no significant differences between wrinkle severity and global aesthetic scores for HA gel implantation alone and HA gel with nonablative IR device treatment at any point. CONCLUSION: Combining the use of a nonablative IR device with HA filler does not appear to be superior to HA filler alone in the treatment of moderate to severe NLF wrinkles. PMID- 22093055 TI - Female soccer knee injury: observed knowledge gaps in injury prevention among players/parents/coaches and current evidence (the KNOW study). AB - This study sought to determine if knowledge regarding the risk for knee injuries and the potential for their prevention is being translated to female adolescent soccer players (13-18 years), their parents, and coaches. Eligible participants in the 2007 indoor soccer season were surveyed to determine their knowledge of the risk for and the potential to prevent knee injuries, and their knowledge of effective prevention strategies, if they felt that injury prevention was possible. Team selection was stratified to be representative of both competitive and recreational level play and age group distributions within the selected soccer association. Of the study subjects, 773/1396 (55.4%) responded to the survey: 408 (53%) players, 292 (38%) parents, and 73 (9%) coaches. Most respondents (538 [71%]) were aware of the risk for knee injury. Coaches and parents were more likely than players to view knee injuries as preventable; however, appropriate prevention strategies were often not identified. Four hundred eighty-four (63.8%) respondents reported that they had never received information on knee injuries. Substantial knowledge gaps regarding knee injury prevention and effective preventative strategies were identified. Given the predominance of knee injuries in female adolescent soccer players, there is an urgent need for knowledge translation of prevention strategies to decrease both incidence and long-term consequences of knee injuries. PMID- 22093056 TI - Development and assessment of the constipation-related disability scale. AB - BACKGROUND: Chronic constipation is associated with impaired quality of life and physical discomfort. Although inability to engage in day-to-day activities has been significantly associated with psychological distress, limited research has examined this relationship in constipated samples. AIM: To develop and validate the Constipation-Related Disability Scale (CRDS), which assesses the extent of disability caused by constipation. METHODS: A total of 240 constipated participants and 103 healthy controls completed the CRDS. Reliability was measured with Cronbach's coefficient alpha and test-retest reliability was assessed with intraclass correlation coefficients. Convergent, divergent and predictive validity were assessed. RESULTS: Component and factor analyses were used to derive two factors: Work/Leisure Activities and Activities of Daily Living, as well as a total CRDS score. Good reliability was found, with alphas >= 0.87 and intraclass correlation coefficients >= 0.85. All scales were negatively correlated with the physical health subscales of the SF-36 (P < 0.001) and were not significantly correlated with the Epworth Sleepiness Scale and Social Desirability Scale, providing support for convergent and divergent validity, respectively. Evidence of predictive validity was supported by associations between the total CRDS with number of physician visits per year (P < 0.01), missed work in the last year (odds ratio [OR = 1.11, 95% confidence interval [CI] = 1.06-1.19, P < 0.001) and ER visits in the last year (OR = 1.08, 95% CI = 1.00 1.16, P < 0.05). CONCLUSIONS: The Constipation-Related Disability Scale is the first instrument that assesses the impact of constipation on daily activities. There is evidence of strong reliability and validity of the instrument. PMID- 22093057 TI - A randomized, double-blind, placebo-controlled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale. AB - Study Type - Therapy (RCT). Level of Evidence 1b. What's known on the subject? and What does the study add? Testosterone deficiency syndrome can be treated with testosterone replacement in the form of injectable, transdermal, buccal and oral preparations. Long-acting i.m. testosterone undecanoate 1000 mg, which is given at 10-14 week intervals, has been shown to be adequate for sustaining normal testosterone levels in hypogonadal men. This study confirms that long-acting i.m. testosterone undecanoate is effective in improving the health-related quality of life in men with testosterone deficiency syndrome as assessed by the improvement in the Aging Male Symptoms scale. Testosterone treatment can be indicated in men who have poor health-related quality of life resulting from testosterone deficiency syndrome. OBJECTIVE: * To evaluate the effect of i.m. injection of testosterone undecanoate 1000 mg over 12 months on the Aging Male Symptom (AMS) scale scores in men with testosterone deficiency syndrome (TDS). PATIENTS AND METHODS: * A total of 120 men >40 years old with TDS (total testosterone < 12 nmol/L and total AMS scores >= 27) were randomized into i.m. injection of either placebo or testosterone undecanoate 1000 mg. * In all, 56 and 58 participants from the active treatment and placebo groups, respectively completed the study. * An i.m. injection of either placebo or testosterone undecanoate 1000 mg was given at weeks 0, 6, 18, 30 and 48. * Self-administered AMS questionnaires were completed at weeks 0, week 18 and week 48. RESULTS: * Improvement in the total AMS score was significantly greater in the treatment group than in the placebo group (F: 4.576, P= 0.017) over the 48-week period. * The mean (sd) total AMS score was 38.46 (11.85) at baseline and 33.59 (1.69) at 48 weeks for the placebo group, and 41.73 (12.73) at baseline and 32.61 (9.67) at 48 weeks for the treatment group. * The mean change in the total AMS score was -12.6% in the placebo group and -21.9% in the treatment group. * The mean psychological and somatovegetative domain scores decreased significantly more in the treatment group than in the placebo group (-2.8 vs -1.2, P= 0.03; and -3.2 vs -1.8, P= 0.016). * The difference in change between the randomized groups for the sexual domain scores followed the same trend, though the difference was not significant. CONCLUSION: * Long-acting testosterone is effective in improving health-related quality of life as assessed by the AMS scale in men with TDS. PMID- 22093058 TI - Acclimatization improves submaximal exercise economy at 5533 m. AB - We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty-two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6-7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (W(max)) decreased from mean +/- SD 356 +/- 73 watts at 490 m to 191 +/- 49 watts and 193 +/- 45 watts at 5533 m, days 6-7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max ) were 50.7 +/- 9.5, 26.3 +/- 5.6, 24.7 +/- 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6-7 (5533 m), VO(2) at 75% W(max) (152 +/- 37 watts) was 1.75 +/- 0.45 L/min, oxygen saturation 68 +/- 8%. On day 11 (5533 m), at the same submaximal work rate, VO(2) was lower (1.61 +/- 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 +/- 7%, P < 0.0004) but ratios of VO(2) to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5-6 but perceived less effort (visual analog scale 50 +/- 15 vs 57 +/- 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions. PMID- 22093059 TI - Decreased gallbladder emptying in dogs with biliary sludge or gallbladder mucocele. AB - Biliary sludge in dogs is dismissed commonly as an incidental finding. On the other hand, gallbladder mucocele is reported increasingly in dogs and can lead to biliary obstruction or gallbladder rupture. Cholestasis is suspected to play a role in development of sludge and mucoceles, though there are no data in dogs to support this. We investigated gallbladder emptying, a key factor in biliary flow, in dogs with mobile sludge, immobile sludge, or gallbladder mucocele and in healthy controls. Gallbladder ejection fraction estimated by ultrasonography was used as the index of gallbladder emptying. The ejection fraction at 60 min after eating was significantly decreased in all three abnormal groups. Moreover, all dogs with sludge or a mucocele had gallbladder distension. These changes were the greatest in the mucocele group. Thus, biliary stasis occurs not only in dogs with gallbladder mucocele but also in dogs with biliary sludge. Cholestasis may play a role in the pathogenesis or progression of these diseases in dogs. PMID- 22093060 TI - Genetic diversity of Mimosa pudica rhizobial symbionts in soils of French Guiana: investigating the origin and diversity of Burkholderia phymatum and other beta rhizobia. AB - The genetic diversity of 221 Mimosa pudica bacterial symbionts trapped from eight soils from diverse environments in French Guiana was assessed by 16S rRNA PCR RFLP, REP-PCR fingerprints, as well as by phylogenies of their 16S rRNA and recA housekeeping genes, and by their nifH, nodA and nodC symbiotic genes. Interestingly, we found a large diversity of beta-rhizobia, with Burkholderia phymatum and Burkholderia tuberum being the most frequent and diverse symbiotic species. Other species were also found, such as Burkholderia mimosarum, an unnamed Burkholderia species and, for the first time in South America, Cupriavidus taiwanensis. The sampling site had a strong influence on the diversity of the symbionts sampled, and the specific distributions of symbiotic populations between the soils were related to soil composition in some cases. Some alpha-rhizobial strains taxonomically close to Rhizobium endophyticum were also trapped in one soil, and these carried two copies of the nodA gene, a feature not previously reported. Phylogenies of nodA, nodC and nifH genes showed a monophyly of symbiotic genes for beta-rhizobia isolated from Mimosa spp., indicative of a long history of interaction between beta-rhizobia and Mimosa species. Based on their symbiotic gene phylogenies and legume hosts, B. tuberum was shown to contain two large biovars: one specific to the mimosoid genus Mimosa and one to South African papilionoid legumes. PMID- 22093061 TI - Acute humoral rejection in pediatric renal transplant recipients receiving steroid minimization immunosuppression. AB - SM protocols have increasingly gained acceptance owing to their favorable side effect profile with comparable cellular rejection rates. After encountering SM patients with AHR, we performed a case-control study to identify predictors associated with AHR in this cohort. Patients with (n = 4) and without (n = 19) biopsy proven AHR on a SM regimen were compared using the Student's t-tests. The median age at transplant was 13.8 yr. Compared to controls, the AHR cohort was older (15.9 vs. 12.1 yr, p = 0.01). Children with AHR had a lower mean tacrolimus trough level and were more likely to have a sub-therapeutic trough at six months (3.5 vs. 5.5 ng/mL, p = 0.05); mean MMF doses were lower at all times points except three months in the AHR group (not statistically significant). This occurred in spite of higher MPA trough levels at all study points in the AHR group (significant at 3 [p = 0.019] and 6 [p = 0.03] months). Children receiving a SM regimen have a lower safety net and may benefit from more intensive monitoring of tacrolimus exposure. MMF dose modifications based on MPA trough determinations should be resisted in the setting of SM. PMID- 22093062 TI - The benefits and risks of stem cell technology. AB - The potential impact of stem cell technology on medical and dental practice is vast. Stem cell research will not only provide the foundation for future therapies, but also reveal unique insights into basic disease mechanisms. Therefore, an understanding of stem cell technology will be necessary for clinicians in the future. Herein, we give a basic overview of stem cell biology and therapeutics for the practicing clinician. PMID- 22093063 TI - Chromatophoroma in a crevice kelpfish (Gibbonsia montereyensis). AB - A captive adult crevice kelpfish, Gibbonsia montereyensis, developed a cutaneous mass, approximately 9 * 7 mm on the right side of the head in an area of nonscaled skin. Following surgical debulking, examination of both impression smears and histologic sections of the tumor revealed a predominant population of round to spindloid to polygonal cells with a moderate amount of lightly basophilic cytoplasm. The cytoplasm was filled with round, variably-sized reddish brown granules that often obscured the nucleus. Nuclei were round to ovoid with coarsely granular chromatin. There was minimal anisocytosis and anisokaryosis. The cytoplasmic granules in histologic sections were weakly positive by the Fontana-Masson method, and staining was eliminated with melanin bleach. Immunohistochemical staining was strongly positive with a murine monoclonal antibody for melan A. As the specificity of melan A for melanophores is not clearly defined in nonmammalian species, the tumor was examined by transmission electron microscopy. Melanophores were not detected. Instead, neoplastic cells were filled with numerous intracytoplasmic organelles with triple-limiting membranes composed of concentric lamellae; these structures were most compatible with pterinosomes, which are the pigment-containing organelles of cells called xanthophores and erythrophores. As both of these organelles are ultrastructurally indistinguishable and as kelpfish skin is known to contain both xanthophores and erythrophores, a diagnosis of a mixed pigment cell tumor or chromatophoroma was made. As the tumor was grossly reddish-brown, the possibility of a neoplastic population of only erythrophores could not be excluded. Pigment cell tumors, arising from cells of the embryonic neural crest, are common in reptiles and bony fish. PMID- 22093064 TI - Development of a novel set of Gateway-compatible vectors for live imaging in insect cells. AB - Insect genomics is a growing area of research. To exploit fully the genomic data that are being generated, high-throughput systems for the functional characterization of insect proteins and their interactomes are required. In this work, a Gateway-compatible vector set for expression of fluorescent fusion proteins in insect cells was developed. The vector set was designed to express a protein of interest fused to any of four different fluorescent proteins [green fluorescent protein (GFP), cyan fluorescent protein (CFP), yellow fluorescent protein (YFP) and mCherry] by either the C-terminal or the N-terminal ends. Additionally, a collection of organelle-specific fluorescent markers was assembled for colocalization with fluorescent recombinant proteins of interest. Moreover, the vector set was proven to be suitable for simultaneously detecting up to three proteins by multiple labelling. The use of the vector set was exemplified by defining the subcellular distribution of Mal de Rio Cuarto virus (MRCV) outer coat protein P10 and by analysing the in vivo self-interaction of the MRCV viroplasm matrix protein P9-1 in Forster resonance energy transfer (FRET) experiments. In conclusion, we have developed a valuable tool for high throughput studies of protein subcellular localization that will aid in the elucidation of the function of newly described insect and virus proteins. PMID- 22093065 TI - Identification of RCN1 and RSA3 as ethanol-tolerant genes in Saccharomyces cerevisiae using a high copy barcoded library. AB - Saccharomyces cerevisiae (S. cerevisiae) encounters a multitude of stresses during industrial processes such as wine fermentation including ethanol toxicity. High levels of ethanol reduce the viability of yeast and may prevent completion of fermentation. The identification of ethanol-tolerant genes is important for creating stress-resistant industrial yeast, and S. cerevisiae genomic resources have been utilized for this purpose. We have employed a molecular barcoded yeast open reading frame (MoBY-ORF) high copy plasmid library to identify ethanol tolerant genes in both the S. cerevisiae S288C laboratory and M2 wine strains. We find that increased dosage of either RCN1 or RSA3 improves tolerance of S288C and M2 to toxic levels of ethanol. RCN1 is a regulator of calcineurin, whereas RSA3 has a role in ribosome maturation. Additional fitness advantages conferred upon overproduction of RCN1 and RSA3 include increased resistance to cell wall degradation, heat, osmotic and oxidative stress. We find that the M2 wine yeast strain is generally more tolerant of stress than S288C with the exception of translation inhibition, which affects M2 growth more severely than S288C. We conclude that regulation of ribosome biogenesis and ultimately translation is a critical factor for S. cerevisiae survival during industrial-related environmental stress. PMID- 22093066 TI - Identification of a Dau c PRPlike protein (Dau c 1.03) as a new allergenic isoform in carrots (cultivar Rodelika). AB - BACKGROUND: Up to 25% of food allergic subjects in central Europe suffer from carrot allergy. Until now, two isoforms of the major carrot (Daucus carota) allergen Dau c 1 have been described: Dau c 1.01, comprising five variants (Dau c 1.0101-Dau c 1.0105) and Dau c 1.02. OBJECTIVE: To investigate potential allergenic properties of a Dau c PRPlike protein, a novel isoform of the PR-10 protein family in carrot. METHODS: Dau c PRPlike cDNA from carrot roots (cv Rodelika) was cloned after RT-PCR and 5'RACE. Dau c PRPlike protein was expressed in E. coli, purified under native conditions by Ni-NTA chromatography and analysed by CD spectroscopy. Immuno-reactivity of the rDau c PRPlike protein was compared with rDau c 1.0104 and rDau c 1.0201 in terms of IgE binding (immunoblotting, ImmunoCAP), IgE cross-reactivity (ELISA inhibition) and in vitro mediator release with sera from carrot allergic patients. mRNA expression of Dau c PRPlike protein in wild-type and transgenic carrot roots was analysed by qRT PCR. RESULTS: The Dau c PRPlike protein was identified as a new allergenic isoform, Dau c 1.03, in carrot roots. 68% of carrot allergic patients were sensitized to rDau c 1.03. The IgE-reactivity of rDau c 1.03 strongly correlated with reactivity to rDau c 1.0104, but not to rDau c 1.0201. The extent of IgE cross-reactivity and allergenic potency of Dau c 1 isoforms varied between the individual sera tested. Dau c 1.03 mRNA transcripts were up-regulated in Dau c 1.01 and Dau c 1.02 gene-silenced carrot roots. CONCLUSION AND CLINICAL RELEVANCE: Dau c 1 isoforms display distinct IgE epitope heterogeneity. Dau c 1.03 appears to contribute to the allergenicity of carrots and the manifestation of carrot allergy. The epitope diversity of different Dau c 1 isoforms should be considered for component-resolved diagnosis and gene silencing of carrot allergens. PMID- 22093067 TI - Reactions of non-immunologic contact urticaria on scalp, face, and back. AB - BACKGROUND: This study compared the reactivity of scalp, face, and back to nonimmunologic contact urticants (NICU) to ascertain relative responsiveness. METHODS: Model urticants, benzoic acid (BA) and hexyl nicotinate (HN) with 3 concentrations of each were applied to marked skin of 10 bald males during 6 weeks. One urticant was applied to one side of nasolabial fold, back, and scalp and the other applied to the contralateral side. Reactivity was assessed by visual scores (VS) and biophysical instruments. Subjects ranked skin sensation with a 10-point visual analogue scale. RESULTS: With 0.25% HN application, upper back VS significantly (p<0.05) exceeded scalp and back VS also showed significantly (p<0.05) stronger reaction than face at 60 min post-application; however, at 2.5% BA site, VS of face exhibited significantly (p<0.05) higher than back at 15 min post-application but with 0.625% BA site, VS of back was significantly (p<0.05) higher than face. The a* value was significantly (p<0.05) higher on back than scalp with 0.625% BA treatment. CONCLUSION: Thus symptoms and measurements vary among sites. Differences may be related to solubility related percutaneous penetration. We encourage investigation into this relatively neglected but clinically important arena, to help explain difference in consumer/patient acceptance of topical formulations. PMID- 22093069 TI - An endo-beta-N-acetylglucosaminidase from Enterococcus faecalis V583 responsible for the hydrolysis of high-mannose and hybrid-type N-linked glycans. AB - It has been demonstrated previously that Enterococcus faecalis produces secreted endoglycosidases that enable the bacteria to remove N-linked glycans from glycoproteins. One enzyme potentially responsible for this activity is EF0114, comprising a typical GH18 endoglycosidase domain and a GH20 domain. We have analyzed the other candidate, EF2863, and show that this predicted single domain GH18 protein is an endo-beta-N-acetylglucosaminidase. EF2863 hydrolyzes the glycosidic bond between two N-acetylglucosamines (GlcNAc) in N-linked glycans of the high-mannose and hybrid type, releasing the glycan and leaving one GlcNAc attached to the protein. The activity of EF2863 is similar to that of the well known deglycosylating enzyme EndoH from Streptomyces plicatus. According to the CAZy nomenclature, the enzyme is designated EfEndo18A. PMID- 22093070 TI - Feed consumption, diet digestibility and mineral utilization in captive blackbuck (Antelope cervicapra) fed different levels of concentrates. AB - A feeding trial was conducted to know the level of concentrates in the diet of Antelope cervicapra at which diet digestibility and mineral utilization were optimum. Fifteen blackbucks (25-33 kg BW) were distributed into three groups of five each. Fresh oat (Avena sativa) and berseem (Trifolium alexandrinum) fodders were offered ad libitum to all the animals. In addition, animals in groups II and III received concentrate mixture at the rate of 0.5 and 1% of BW, whereas animals in group I received no concentrates. As the level of concentrates increased, consumption of fodder decreased resulting in decreased consumption of neutral detergent fibre (NDFom), acid detergent fibre (ADFom), hemicellulose and cellulose. However, overall total dry matter (DM) and organic matter (OM) intake was not significantly different between the groups. Digestibility of DM, OM and gross energy (GE) increased while that of NDFom and ADFom decreased with increased level of concentrates in the diet. Intake of P, Zn, Cu and Mn increased with increased level of concentrate supplementation; however, consumption of Ca and Fe followed the reverse trend. Absorption of P and Zn increased with increased level of concentrate supplementation. Serum concentration of Zn increased when concentrate was supplemented at the rate of 0.5% BW beyond which there was no further improvement. Increasing the level of concentrates in the diet was resulted in increased serum glucose and cholesterol levels. Forage-only diet was inadequate in supply of energy, P and zinc. Supplementation of concentrates at the rate of 0.5% BW was able to meet the requirement of these nutrients. Supplementation at the rate of 1% BW supplied energy and P in excess of requirement. It was concluded that the feeding of concentrates to the captive blackbuck fed forage-based diets should be restricted to 0.5% of BW. PMID- 22093071 TI - Acute effects of fractional laser on photo-aged skin. AB - BACKGROUND: Nonablative fractional photothermolysis (FP) laser treatment has shown clinical efficacy on photo-aged skin. Few studies have examined the molecular responses to FP. OBJECTIVE: To characterize the dynamic alterations involved in dermal matrix remodeling after FP laser treatment. METHODS: A single multipass FP treatment was performed. Baseline, day 1, and day 7 biopsies were obtained. Biopsies were sectioned and stained for histology and immunofluorescence confocal microscopic. Heat shock protein-70 (HSP-70) and matrix metalloproteinase-1 (MMP-1) expression and extracellular matrix (ECM) autofluorescence were examined. Quantitative real-time polymerase chain reaction (qRT-PCR) experiments were performed probing for collagen 1A1 (COL1A1) and COL3A1. RESULTS: All three patients were Caucasian women aged 49, 62, and 64 with Fitzpatrick skin types II, III, and IV. Transient neutrophilic infiltration found on day 1. Protein expression of HSP-70 and MMP-1 were up-regulated on day 1, reverting to baseline by day 7. ECM autofluorescence decreased from baseline to day 7. qRT-PCR showed a minor decrease in COL1A1 and COL3A1 messenger RNA 1 day after treatment. Variable results between patients receiving equal treatment were evident. PMID- 22093072 TI - The cytocompatibility and osseointegration of the Ti implants with XPEED(r) surfaces. AB - OBJECTIVES: This study evaluated cytocompatibility and osseointegration of the titanium (Ti) implants with resorbable blast media (RBM) surfaces produced by grit-blasting or XPEED((r)) surfaces by coating of the nanostructured calcium. MATERIAL AND METHODS: Ti implants with XPEED((r)) surfaces were hydrothermally prepared from Ti implants with RBM surfaces in a solution containing alkaline calcium. The surface characteristics were evaluated by using a scanning electron microscope (SEM) and surface roughness measuring system. Apatite formation was measured with SEM after immersion in modified-simulated body fluid and the amount of calcium released was measured by inductively coupled plasma optical emission. The cell proliferation was investigated by MTT assay and the cell attachment was evaluated by SEM in MC3T3-E1 pre-osteoblast cells. Thirty implants with RBM surfaces and 30 implants with XPEED((r)) surfaces were placed in the proximal tibiae and in the femoral condyles of 10 New Zealand White rabbits. The osseointegration was evaluated by a removal torque test in the proximal tibiae and by histomorphometric analysis in the femoral condyles 4 weeks after implantation. RESULTS: The Ti implants with XPEED((r)) surfaces showed a similar surface morphology and surface roughness to those of the Ti implants with RBM surfaces. The amount of calcium ions released from the surface of the Ti implants with XPEED((r)) surfaces was much more than the Ti implants with RBM surfaces (P < 0.05). The cell proliferation and cell attachment of the Ti implants showed a similar pattern to those of the Ti implants with RBM surfaces (P > 0.1). Apatite deposition significantly increased in all surfaces of the Ti implants with XPEED((r)) surfaces. The removable torque value (P = 0.038) and percentage of bone-to-implant contact (BIC%) (P = 0.03) was enhanced in the Ti implants with XPEED((r)) surfaces. CONCLUSION: The Ti implants with XPEED((r)) surfaces significantly enhanced apatite formation, removal torque value, and the BIC%. The Ti implants with XPEED((r)) surfaces may induce strong bone integration by improving osseointegration of grit-blasted Ti implants in areas of poor quality bone. PMID- 22093073 TI - Potential impact of surgical periodontal therapy on oral health-related quality of life in patients with periodontitis: a pilot study. AB - AIM: To gain insight into the impact of periodontal surgery on oral health related quality of life (QoL) of patients with periodontitis. MATERIAL AND METHODS: Study participants were recruited from moderate to severe periodontitis patients. After initial periodontal therapy, participants received periodontal surgery. Oral Health-related Quality of Life Model for Dental Hygiene (OHRQL) was used to assess participant's QoL at each time point of periodontal evaluation (baseline, at least 3 weeks after initial therapy and 3-4 months after surgery). RESULTS: A total of 21 patients completed OHRQL assessment after surgery. Compared with baseline, a progressive improvement in periodontal parameters was observed during the periodontal therapy. The total mean OHRQL score at baseline (25.5 +/- 11.4) was significantly reduced (improved) after initial therapy and after surgery (16.7 +/- 9.5 and 15.0 +/- 9.7, respectively; p < 0.01). However, no significant difference was found between the OHRQL score after initial therapy and that after surgery. CONCLUSIONS: No significant differences in patients' oral health-related QoL were observed between post-initial therapy and post-surgery intervals, although a tendency of surgery to determine an improvement in QoL was observed when compared with post-initial treatment. PMID- 22093074 TI - Urinary concentrations of 15-epimer of lipoxin A(4) are lower in patients with aspirin-intolerant compared with aspirin-tolerant asthma. AB - BACKGROUND: Although an abnormality in arachidonic acid metabolism may be responsible for aspirin-intolerant asthma (AIA), there is little knowledge about the concentrations of urinary lipoxin A(4) (LXA(4)) and the 15-epimer of LXA(4) (15-epi-LXA(4)) in relation to asthma severity in AIA subjects. OBJECTIVE: The purpose of this study is to estimate urinary LXA(4) and the 15-epimer concentrations to investigate lipoxins in AIA. METHODS: In this study, we examined AIA, aspirin-tolerant asthma (ATA) and healthy control groups. The AIA and ATA groups were subdivided into the severe asthma and non-severe asthma subgroups. Urinary LXA(4), 15-epi-LXA(4) and leukotriene E(4) (LTE(4) ) were quantified using enzyme immunoassay after separating these compounds using high performance liquid chromatography. RESULTS: The urinary LXA(4) concentration was significantly lower than the 15-epi-LXA(4) concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15-epi-LXA(4) (P < 0.01) and higher urinary LTE(4) concentrations (P < 0.05) than the ATA group. Comparison of 15-epi-LXA(4) concentrations between the severe asthmatic and non severe asthmatic subjects in the AIA and ATA groups revealed that the decreased 15-epi-LXA(4) concentration may be related to aspirin intolerance, but not asthma severity. Receiver operator characteristic curves demonstrated that the concentration ratio of LTE(4) to 15-epi-LXA(4) was superior to 15-epi-LXA(4) concentration and LTE(4) concentration as a predictive factor for aspirin intolerance. CONCLUSIONS AND CLINICAL RELEVANCE: We have demonstrated for the first time that urinary 15-epi-LXA(4) concentration is significantly higher than LXA(4) concentration in both the AIA and ATA groups. 15-Epi-LXA(4) concentration was significantly lower in the AIA group with an increased urinary LTE(4) concentration than in the ATA group. An imbalance between proinflammatory cysteinyl-leukotrienes and anti-inflammatory 15-epi-LXA(4) may be involved in AIA pathogenesis. PMID- 22093075 TI - Clinical impact of the use of 16S rRNA sequencing method for the identification of "difficult-to-identify" bacteria in immunocompromised hosts. AB - Molecular method of 16S rRNA sequencing is reported to be helpful in the accurate identification of organisms with ambiguous phenotypic profiles. We analyzed the use of 16S rRNA sequencing method to identify clinically significant, "difficult to-identify" bacteria recovered from clinical specimens, and evaluated its role in patient management and consequent clinical outcome. Among the 172 "difficult to-identify" bacteria recovered over a 4-year period, 140 were gram-positive cocci or gram-negative bacilli; identification by 16S rRNA did not play a role in the management of patients infected with these bacteria. From 32 patients, 33 "difficult-to-identify" gram-positive bacilli were identified; the organisms were mycobacteria, Nocardia, Tsukamurella, Rhodococcus, and Gordonia. In 24 patients for whom clinical data were available, results from the 16S rRNA sequencing method led to treatment change in 14 immunocompromised patients (including 7 hematopoietic stem cell recipients and 1 liver transplant recipient). Therapy was modified in 9 patients, initiated in 3 patients, and discontinued in 2 patients. Most patients' therapy was switched to oral antibiotics with discontinuation of intravascular catheters, facilitating early hospital discharge. All 14 patients were alive 30 days after infection onset. The present study demonstrates the clinical application of 16S rRNA sequencing method to identify "difficult-to identify" mycobacteria and other gram-positive bacilli in clinical specimens, particularly in immunocompromised hosts. PMID- 22093076 TI - RCT comparing minimally with moderately rough implants. Part 2: microbial observations. AB - BACKGROUND: Most current implants have a moderately rough surface (compared with older minimally rough "turned" implants) to facilitate osseointegration. This randomized controlled trial (RCT), with split-mouth design, examined whether this increased surface roughness influenced the initial subgingival plaque formation. MATERIAL AND METHODS: Ten fully edentulous and eight partially edentulous patients, all with a history of severe periodontitis, received 4-6 implants (mandible or maxilla). Per jaw, both minimally (turned) and moderately rough (TiUnite) implants (MKIII; Nobel Biocare) were alternated. Also, the healing and final abutments had similar surface characteristics. Subgingival biofilm formation was followed up for 1 year, and samples were analyzed by culture technique, qPCR and checkerboard RESULTS: Over the entire period, no statistically significant differences could be detected in subgingival microbiota between the minimally and moderately rough surfaces. In partially edentulous patients, the biofilm matured to a higher concentration of pathogens when compared with fully edentulous patients. The subgingival implant composition and concentration in partially edentulous patients were comparable to the subgingival microbiota along teeth. CONCLUSION: The roughness of the more modern implants did not influence the biofilm formation during the first year of implant loading. PMID- 22093077 TI - African ancestry, early life exposures, and respiratory morbidity in early childhood. AB - BACKGROUND: Racial disparities persist in early childhood wheezing and cannot be completely explained by known risk factors. OBJECTIVE: To evaluate the associations of genetic ancestry and self-identified race with early childhood recurrent wheezing, accounting for socio-economic status (SES) and early life exposures. METHODS: We studied 1034 children in an urban, multi-racial, prospective birth cohort. Multivariate logistic regression was used to evaluate the association of genetic ancestry as opposed to self-identified race with recurrent wheezing (>3 episodes). Sequential models accounted for demographic, socio-economic factors and early life risk factors. Genetic ancestry, estimated using 150 ancestry informative markers, was expressed in deciles. RESULTS: Approximately 6.1% of subjects (mean age 3.1 years) experienced recurrent wheezing. After accounting for SES and demographic factors, African ancestry (OR: 1.16, 95% CI: 1.02-1.31) was significantly associated with recurrent wheezing. By self-reported race, hispanic subjects had a borderline decrease in risk of wheeze compared with African Americans (OR: 0.44, 95% CI: 0.19-1.00), whereas white subjects (OR: 0.46, 95% CI: 0.14-1.57) did not have. After further adjustment for known confounders and early life exposures, both African (OR: 1.19, 95% CI: 1.05 1.34) and European ancestry (OR: 0.84, 95% CI: 0.74-0.94) retained a significant association with recurrent wheezing, as compared with self-identified race (OR(whites) : 0.31, 95% CI: 0.09-1.14; OR(hispanic) : 0.47, 95% CI: 0.20-1.08). There were no significant interactions between ancestry and early life factors on recurrent wheezing. CONCLUSIONS AND CLINICAL RELEVANCE: In contrast to self identified race, African ancestry remained a significant, independent predictor of early childhood wheezing after accounting for early life and other known risk factors associated with lung function changes and asthma. Genetic ancestry may be a powerful way to evaluate wheezing disparities and a proxy for differentially distributed genetic and early life risk factors associated with childhood recurrent wheezing. PMID- 22093078 TI - Early peri-implant endosseous healing of two implant surfaces placed in surgically created circumferential defects. A histomorphometric and fluorescence study in dogs. AB - OBJECTIVE: Several implant surfaces are being developed, some in the nanoscale level. In this study, two different surfaces had their early healing properties compared in context of circumferential defects of various widths. MATERIAL AND METHODS: Six dogs had the mandibular premolars extracted. After 8 weeks, four implants were placed equicrestally in each side. One acted as control, while the others were inserted into sites with circumferential defects of 1.0, 1.5 and 2.0 mm wide and 5 mm deep. A nano-modified surface was used on one side and a micro rough on the other. Bone markers were administered on the third day after implant placement and then after 1, 2, 4 weeks to investigate the bone formation dynamic through fluorescence analysis. Ground sections were prepared from 8-week healing biopsies and histomorphometry was performed. RESULTS: The fluorescence evaluation of the early healing showed numerically better results for the nano-modified group; however this trend was not followed by the histomorphometric evaluation. A non-significant numerical superiority of the micro-rough group was observed in terms of vertical bone apposition, defect bone fill, bone-to-implant contact and bone density. In the intra-group analysis, the wider defects showed the worse results while the control sites showed the best results for the different parameters, but without statistical relevance. CONCLUSION: Both surfaces may lead to complete fill of circumferential defects, but the gap width has to be considered as a challenge. The nano-scale modification was beneficial in the early stages of bone healing, but the micro-rough surface showed numerical better outcomes at the 8-week final period. PMID- 22093079 TI - Evolutionary origin of the Rhodobacter sphaeroides specialized RpoN sigma factors. AB - Gene duplication and horizontal gene transfer (HGT) are two events that enable the generation of new genes. Rhodobacter sphaeroides (WS8 and 2.4.1 strains) has four copies of the rpoN gene that are not functionally interchangeable. Until now, this is the only example of specialization of this sigma factor. In this work, we aimed to determine whether the multiple copies of this gene originated from HGT or through gene duplication. Our results suggest a multiplication origin of the different rpoN copies that occurred after the Rhodobacter clade separated. Functional tests indicate that the specialization of the rpoN genes is not restricted to R. sphaeroides. We propose that the rpoN copy involved in nitrogen fixation is the ancestral gene and that the other rpoN genes have acquired new specificities. PMID- 22093080 TI - The impact of dietary induced hyperparathyroidism on healthy and diseased periodontia: an experimental study in rats. AB - BACKGROUND AND OBJECTIVE: Nutrition may be a potential modifying factor in periodontal conditions. The present study investigated this phenomenon for dietary induced hyperparathyroidism (dHPT) by revealing the histopathological and histomorphometrical profiles of healthy and diseased periodontia in dHPT. METHODS: Dietary induced hyperparathyroidism was induced in 12 rats by dietary calcium/phosphorous imbalance and 12 rats were fed standard diet (SD). Periodontitis was induced on the right mandibular molar teeth (mmt) of these rats by injecting an endotoxin + saline solution whereas injecting pure saline to the left mmt. Thus, four study groups were created: dHPT + saline (group 1), dHPT + endotoxin (group 2), SD + endotoxin (group 3) and SD + saline (group 4). Histological sections were obtained from the second mmt and examined using light microscope. RESULTS: Group 1 demonstrated inflammatory and degenerative alterations in periodontium without pocket formation. Periodontitis was evident in groups 2 and 3. Group 2 revealed the highest amounts of gingival inflammatory cell and vessel counts (group 2 > group 3 > group 1 > group 4), attachment and bone losses (group 2 > group 3 > groups 1 > group 4) and osteoclast count (group 2 > group 3 > group 1 > group 4) (p < 0.05). CONCLUSION: These results propose that dHPT may impair the health status of periodontium and may worsen the pathobiology of periodontal diseases. PMID- 22093081 TI - The role of massage in scar management: a literature review. AB - BACKGROUND: Many surgeons recommend postoperative scar massage to improve aesthetic outcome, although scar massage regimens vary greatly. OBJECTIVE: To review the regimens and efficacy of scar massage. METHODS: PubMed was searched using the following key words: "massage" in combination with "scar," or "linear," "hypertrophic," "keloid," "diasta*," "atrophic." Information on study type, scar type, number of patients, scar location, time to onset of massage therapy, treatment protocol, treatment duration, outcomes measured, and response to treatment was tabulated. RESULTS: Ten publications including 144 patients who received scar massage were examined in this review. Time to treatment onset ranged from after suture removal to longer than 2 years. Treatment protocols ranged from 10 minutes twice daily to 30 minutes twice weekly. Treatment duration varied from one treatment to 6 months. Overall, 65 patients (45.7%) experienced clinical improvement based on Patient Observer Scar Assessment Scale score, Vancouver Scar Scale score, range of motion, pruritus, pain, mood, depression, or anxiety. Of 30 surgical scars treated with massage, 27 (90%) had improved appearance or Patient Observer Scar Assessment Scale score. CONCLUSIONS: The evidence for the use of scar massage is weak, regimens used are varied, and outcomes measured are neither standardized nor reliably objective, although its efficacy appears to be greater in postsurgical scars than traumatic or postburn scars. Although scar massage is anecdotally effective, there is scarce scientific data in the literature to support it. PMID- 22093082 TI - Adherence to the European Society of Cardiology (ESC) guidelines for chronic heart failure--a national survey of the cardiologists in Pakistan. AB - BACKGROUND: The aims of this study were to evaluate the awareness of and attitudes towards the 2005 European Society of Cardiology (ESC) guidelines for Heart Failure (HF) of the cardiologists in Pakistan and assess barriers to adherence to guidelines. METHODS: A cross-sectional survey was conducted in person from March to July 2009 to all cardiologists practicing in 4 major cities in Pakistan (Karachi, Lahore, Quetta and Peshawar). A validated, semi-structured questionnaire assessing ESC 2005 Guidelines for HF was used to obtain information from cardiologists. It included questions about awareness and relevance of HF guidelines (See Additional File 1). Respondents' management choices were compared with those of an expert panel based on the guidelines for three fictitious patient cases. Cardiologists were also asked about major barriers to adherence to guidelines. RESULTS: A total of 372 cardiologists were approached; 305 consented to participate (overall response rate, 82.0%). The survey showed a very high awareness of CHF guidelines; 97.4% aware of any guideline. About 13.8% considered ESC guidelines as relevant or very relevant for guiding treatment decisions while 92.8% chose AHA guidelines in relevance. 87.2% of respondents perceived that they adhered to the HF guidelines. For the patient cases, the proportions of respondents who made recommendations that completely matched those of the guidelines were 7% (Scenario 1), 0% (Scenario 2) and 20% (Scenario 3). Respondents considered patient compliance (59%) and cost/health economics (50%) as major barriers to guideline implementation. CONCLUSION: We found important self reported departures from recommended HF management guidelines among cardiologists of Pakistan. PMID- 22093083 TI - Towards continuous improvement of endoscopy standards: validation of a colonoscopy assessment form. AB - AIM: The assessment of procedural colonoscopy skills is important and topical. The aim of this study was to develop and validate a competency-based colonoscopy assessment form that would be easy to use, suitable for the assessment of junior and senior endoscopists and potentially a useful instrument to detect differences in performance standards following different training interventions. METHOD: A standardized assessment form was developed incorporating a checklist with dichotomous yes/no responses and a global assessment section incorporating several different elements. This form was used prospectively to evaluate colonoscopy cases during the period of the study in several university teaching hospitals. Results were analysed using ANOVA with Bonferroni corrections for post hoc analysis. RESULTS: Eighty-one procedures were assessed, performed by eight consultant and 19 trainee endoscopists. There were no serious errors. When divided into three groups based on previous experience (novice, intermediate and expert) the assessment form demonstrated statistically significant differences between all three groups (P<0.05). When separate elements were taken into account, the global assessment section was a better discriminator of skill level than the checklist. CONCLUSION: This form is a valid, easy-to-use assessment method. We intend to use it to assess the value of simulator training in trainee endoscopists. It also has the potential to be a useful training tool when feedback is given to the trainee. PMID- 22093084 TI - Infant mortality in South Africa--distribution, associations and policy implications, 2007: an ecological spatial analysis. AB - BACKGROUND: Many sub-Saharan countries are confronted with persistently high levels of infant mortality because of the impact of a range of biological and social determinants. In particular, infant mortality has increased in sub-Saharan Africa in recent decades due to the HIV/AIDS epidemic. The geographic distribution of health problems and their relationship to potential risk factors can be invaluable for cost effective intervention planning. The objective of this paper is to determine and map the spatial nature of infant mortality in South Africa at a sub district level in order to inform policy intervention. In particular, the paper identifies and maps high risk clusters of infant mortality, as well as examines the impact of a range of determinants on infant mortality. A Bayesian approach is used to quantify the spatial risk of infant mortality, as well as significant associations (given spatial correlation between neighbouring areas) between infant mortality and a range of determinants. The most attributable determinants in each sub-district are calculated based on a combination of prevalence and model risk factor coefficient estimates. This integrated small area approach can be adapted and applied in other high burden settings to assist intervention planning and targeting. RESULTS: Infant mortality remains high in South Africa with seemingly little reduction since previous estimates in the early 2000's. Results showed marked geographical differences in infant mortality risk between provinces as well as within provinces as well as significantly higher risk in specific sub-districts and provinces. A number of determinants were found to have a significant adverse influence on infant mortality at the sub-district level. Following multivariable adjustment increasing maternal mortality, antenatal HIV prevalence, previous sibling mortality and male infant gender remained significantly associated with increased infant mortality risk. Of these antenatal HIV sero-prevalence, previous sibling mortality and maternal mortality were found to be the most attributable respectively. CONCLUSIONS: This study demonstrates the usefulness of advanced spatial analysis to both quantify excess infant mortality risk at the lowest administrative unit, as well as the use of Bayesian modelling to quantify determinant significance given spatial correlation. The "novel" integration of determinant prevalence at the sub-district and coefficient estimates to estimate attributable fractions further elucidates the "high impact" factors in particular areas and has considerable potential to be applied in other locations. The usefulness of the paper, therefore, not only suggests where to intervene geographically, but also what specific interventions policy makers should prioritize in order to reduce the infant mortality burden in specific administration areas. PMID- 22093085 TI - The effect of ergometer design on rowing stroke mechanics. AB - The effect of rowing ergometer design upon power delivery and coordination patterns of the rowing stroke was analyzed for 14 elite rowers. Rowers were tested in three ergometer conditions: the fixed stretcher Concept2c ergometer, the Concept2c ergometer mounted on sliding rails, and the sliding stretcher RowPerfect ergometer. Ergometers were instrumented to measure the external force generated at the handle and the foot stretcher and a nine-segment inverse dynamics model used to calculate joint and overall power delivery. Peak power generation and absorption at the knee joint was significantly greater, and total power delivered to the ergometer delayed on the fixed stretcher ergometer when compared to the sliding stretcher ergometers. No differences were found in the mechanical energy delivered to the handle of the three ergometers; however, greater joint mechanical energy production of the lower limb reduced mechanical efficiency when rowing the Concept2c fixed ergometer. The fixed foot stretcher on the Concept2c fixed ergometer acts to increase the inertial forces that the rower must overcome at the catch, increasing the moment and power output at the knee, and affecting the coordination pattern during the recovery phase. PMID- 22093086 TI - Cutaneous ureterostomy using the transverse mesocolon. AB - Cutaneous ureterostomy cannot be carried out by the retroperitoneal method in cases showing an insufficient length of the available ureter. We therefore proposed and carried out cutaneous ureterostomy transperitoneally on a ureter of minimum length using the transverse mesocolon. The right and left ureters are drawn from the retroperitoneum into the peritoneal cavity in the renal hilus area. The right ureter is then led from the root of the transverse mesocolon to the area attached to the transverse colon under the subserous part of the transverse mesocolon, and penetrates the gastrocolic ligament. The left ureter is led to the area attached to the transverse mesocolon under the subserous part of the transverse mesocolon, and penetrates the transverse mesocolon, bursa omentalis and gastrocolic ligament. Next, both the right and left ureters are drawn up to the abdominal wall and a ureterstoma is constructed. The transverse mesocolon can be used as supporting tissue for the ureter. Furthermore, this also ensures blood flow in the ureter. PMID- 22093088 TI - Mammalian lipocalin allergens--insights into their enigmatic allergenicity. AB - Most of the important mammal-derived respiratory allergens, as well as a milk allergen and a few insect allergens, belong to the lipocalin protein family. As mammalian lipocalin allergens are found in dander, saliva and urine, they disperse effectively and are widely present in the indoor environments. Initially, lipocalins were characterized as transport proteins for small, principally hydrophobic molecules, but now they are known to be involved in many other biological functions. Although the amino acid identity between lipocalins is generally at the level of 20-30%, it can be considerably higher. Lipocalin allergens do not exhibit any known physicochemical, functional or structural property that would account for their allergenicity, that is, the capacity to induce T-helper type 2 immunity against them. A distinctive feature of mammalian lipocalin allergens is their poor capacity to stimulate the cellular arm of the human or murine immune system. Nevertheless, they induce IgE production in a large proportion of atopic individuals exposed to the allergen source. The poor capacity of mammalian lipocalin allergens to stimulate the cellular immune system does not appear to result from the function of regulatory T cells. Instead, the T cell epitopes of mammalian lipocalin allergens are few and those examined have proved to be suboptimal. Moreover, the frequency of mammalian lipocalin allergen specific CD4(+) T cells is very low in the peripheral blood. Importantly, recent research suggests that the lipocalin allergen-specific T cell repertoires differ considerably between allergic and healthy subjects. These observations are compatible with our hypothesis that the way CD4(+) T-helper cells recognize the epitopes of mammalian lipocalin allergens may be implicated in their allergenicity. Indeed, as several lipocalins exhibit homologies of 40-60% over species, mammalian lipocalin allergens may be immunologically at the borderline of self and non-self, which would not allow a strong anti-allergenic immune response against them. PMID- 22093087 TI - Evolutionary and functional analyses of cytochrome P4501A promoter polymorphisms in natural populations. AB - The functional importance of variable, transcriptional regulatory sequences within and among natural populations is largely unexplored. We analysed the cytochrome P4501A (CYP1A) promoter in three populations of the minnow, Fundulus heteroclitus, because two SNPs in the promoter and first intron of CYP1A are under selection in populations adapted to pollutants. To define the importance of these SNPs, 1630 bp of the CYP1A promoter and first intron and exon were sequenced in eight individuals from three populations: a population from a polluted environment resistant to some aromatic pollutants and two flanking reference populations. CYP1A is induced by many aromatic pollutants, but in populations adapted to pollutants, CYP1A has been shown to be refractory to induction. We were interested in understanding whether variation in the CYP1A promoter explains mechanism(s) of adaptation to these aromatic pollutants. The CYP1A promoter was extremely variable (an average of 9.3% of the promoter nucleotides varied among all populations) and exhibited no fixed differences between populations. As CYP1A is poorly inducible in adapted fish, we hypothesized that CYP1A promoter regions might vary functionally between populations. Unexpectedly, in vitro analysis showed significantly greater transcription from CYP1A promoters found in the population from the polluted environment relative to promoters found in both reference populations. Thus, despite extensive variation among populations and lack of fixed differences between populations, individuals from a polluted environment have significantly enhanced promoter activity. These data demonstrate that intraspecific variation, which provides the raw material for natural selection to act on, can occur while maintaining promoter function. PMID- 22093089 TI - Analysis of rotavirus antigenemia in hematopoietic stem cell transplant recipients. AB - Systemic rotavirus infection, such as rotavirus antigenemia, has been found in immunocompetent rotavirus gastroenteritis patients. However, the pathogenesis of rotavirus infection in immunocompromised transplant recipients remains unclear. Enzyme-linked immunosorbent assay was used to measure rotavirus antigen levels in serially collected serum samples obtained from 62 pediatric patients receiving allogeneic hematopoietic stem cell transplants (HSCT). Rotavirus antigen was detected in 43 (6.8%) of 633 serum samples (8 of 62 patients). The duration of rotavirus antigenemia ranged between 1 and 10 weeks, and diarrhea was concurrent with rotavirus antigenemia in Cases 3, 6, 7, and 8. The level of viral antigen in the transplant recipients (0.19 +/- 0.20) was significantly lower than that observed in serum samples collected from immunocompetent patients on either day 1 (0.49 +/- 0.18, P = 0.0011) or day 3 (0.63 +/- 0.09, P = 0.0005). A patient who received a graft from a human leukocyte antigen (HLA)-mismatched donor was at significant risk for rotavirus antigenemia (P = 0.024; odds ratio = 9.44) in comparison to patients who received grafts from HLA-matched donors. Although the duration of antigenemia was clearly longer in HSCT patients than in immunocompetent rotavirus gastroenteritis patients, the levels of viral antigen were not as high. Therefore, mismatched HLA may be a risk factor for rotavirus antigenemia after HSCT. PMID- 22093091 TI - Transperineal prostate biopsy detects significant cancer in patients with elevated prostate-specific antigen (PSA) levels and previous negative transrectal biopsies. AB - Several authors have previously reported that transrectal prostate biopsy has a false-negative rate of 20-30%, and that a number of prostate cancers missed on transrectal biopsy can be detected by transperineal biopsy. It has also been shown that most of these tumours are located anteriorly in the prostate gland. The present study showed a high rate of prostate cancer in patients with previous negative transrectal biopsies but elevated PSA levels, and that the cancers were located anteriorly in the prostate gland. Also, most of these cancers were clinically significant in patients that underwent RP, i.e. a high proportion of cancers were high-grade/high-stage tumours. We also showed that the transperineal biopsy technique can be applied successfully to patients with a closed anal orifice after previous surgery for rectal cancer. Transperineal biopsy can be done safely without routine antibiotic prophylaxis. OBJECTIVE: To investigate the outcomes of transperineal prostate biopsies in patients with elevated prostate specific antigen (PSA) levels and negative transrectal biopsies. The aim of this retrospective study was to evaluate the diagnostic yield of the transperineal biopsy approach in these patients, and to evaluate the pathology findings in subsequent radical prostatectomy (RP) specimens in patients undergoing RP. PATIENTS AND METHODS: In all, 69 consecutive patients with previous negative transrectal biopsies but elevated PSA levels investigated at urological units in Norway who had been referred to The Norwegian Radium Hospital were included. The patients had undergone a mean (median; range) of 2.42 (2; 0-7) transrectal biopsies. The mean (range) age was 63.1 (42-78) years. The median (range) PSA level was 12 (4.3-229) ng/mL. The patients were examined with transperineal biopsy of the prostate between July 2007 and February 2009. The results of the transperineal biopsies were reviewed for Gleason biopsy score, and these were compared with the histopathology results of the RP specimens, i.e. final Gleason scores. Pathological stage of the prostate specimens and tumour volume were also reviewed. RESULTS: Prostate cancer was found in the biopsies of 38 of 69 patients (55%). In all, 20 of 38 patients had a Gleason score estimated at >=3 + 4 = 7. In all, 26 patients underwent RP. The surgical specimens revealed pathological stage pT2c in 65%, pT3a in 27% and pT3b in 8% of the cases. In all, 23 of the 26 RP specimens showed a final Gleason score of >=7. The vast majority of cancers detected were situated in the anterior/ventral portion of the prostate. CONCLUSIONS: Transperineal biopsy of the prostate in patients with an elevated PSA level after negative transrectal prostate biopsies appears to be a feasible and important option for further investigation to detect prostate cancer. The present study shows that the transperineal biopsy allows good access of the anterior/ventral part of the prostate. Histopathology reports on the RP specimens obtained from the patients that underwent RP revealed significant cancer. PMID- 22093090 TI - Fractalkine/CX3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death. AB - BACKGROUND: Fractalkine/CX3CL1 and its cognate receptor CX3CR1 are abundantly expressed in the CNS. Fractalkine is an unusual C-X3-C motif chemokine that is important in neuron-microglial communication, a co-receptor for HIV infection, and can be neuroprotective. To assess the effects of fractalkine on opiate-HIV interactive neurotoxicity, wild-type murine striatal neurons were co-cultured with mixed glia from the striata of wild-type or Cx3cr1 knockout mice +/- HIV-1 Tat and/or morphine. Time-lapse digital images were continuously recorded at 20 min intervals for up to 72 h using computer-aided microscopy to track the same cells repeatedly. RESULTS: Co-exposure to Tat and morphine caused synergistic increases in neuron death, dendritic pruning, and microglial motility as previously reported. Exogenous fractalkine prevented synergistic Tat and morphine induced dendritic losses and neuron death even though the inflammatory mediator TNF-alpha remained significantly elevated. Antibody blockade of CX3CR1 mimicked the toxic effects of morphine plus Tat, but did not add to their toxicity; while fractalkine failed to protect wild-type neurons co-cultured with Cx3cr1-/--null glia against morphine and Tat toxicity. Exogenous fractalkine also normalized microglial motility, which is elevated by Tat and morphine co-exposure, presumably limiting microglial surveillance that may lead to toxic effects on neurons. Fractalkine immunofluorescence was expressed in neurons and to a lesser extent by other cell types, whereas CX3CR1 immunoreactivity or GFP fluorescence in cells cultured from the striatum of Cx3cr1-/- (Cx3cr1GFP/GFP) mice were associated with microglia. Immunoblotting shows that fractalkine levels were unchanged following Tat and/or morphine exposure and there was no increase in released fractalkine as determined by ELISA. By contrast, CX3CR1 protein levels were markedly downregulated. CONCLUSIONS: The results suggest that deficits in fractalkine-CX3CR1 signaling contribute to the synergistic neurotoxic effects of opioids and Tat. Importantly, exogenous fractalkine can selectively protect neurons from the injurious effects of chronic opioid-HIV-1 Tat co-exposure, and this suggests a potential therapeutic course for neuroAIDS. Although the cellular mechanisms underlying neuroprotection are not certain, findings that exogenous fractalkine reduces microglial motility and fails to protect neurons co-cultured with Cx3cr1-/- mixed glia suggest that fractalkine may act by interfering with toxic microglial-neuron interactions. PMID- 22093092 TI - T-lymphocyte homeostasis and function in infant baboons: implications for transplantation. AB - Laboratory mice are born lymphopenic and demonstrate lymphopenia-induced proliferation that generates memory T cells, yet they are prone to immunologic tolerance. Here we tested whether these fundamental immunologic observations apply to higher animals by studying the immune system of infant baboons. Using flow cytometry of the peripheral blood cells, it was found that baboons are born relatively lymphopenic and subsequently expand their initially naive T cell pool with increasing numbers of memory T cells. After transplantation of an artery patch allograft or xenograft, non-immunosuppressed recipients readily mounted an immune response against donor-type antigens, as evidenced by mixed lymphocyte reaction. Immunosuppression with anti-thymocyte globulin (ATG), anti-CD154 mAb, and mycophenolate mofetil prevented T cell-mediated rejection. After lymphocyte depletion with ATG, homeostatic T cell proliferation was observed. In conclusion, the baboon proved a suitable model to investigate the infant immune system. In this study, neonatal lymphopenia and expansion of the memory T cell population were observed but, unlike mice, there were no indications that infant baboons are prone to T cell tolerance. The expansion of memory T cells during the neonatal period or after induction therapy may actually form an obstacle to tapering immunosuppressive therapy, or ultimately achieving immunologic tolerance. PMID- 22093093 TI - Development and characterization of a human dermal equivalent with physiological mechanical properties. AB - BACKGROUND/AIMS: Different models of reconstructed skin are available, either to provide skin wound healing when this process is deficient, or to be used as an in vitro model. Nevertheless, few studies have focused on the mechanical properties of skin equivalent. Indeed, human skin is naturally under tension. Taking into account these features, the purpose of this work was to obtain a cellularized dermal equivalent (CDE), composed of collagen and dermal fibroblasts. METHODS: To counteract the natural retraction of CDE and to maintain it under tension, different biomaterials were tested. Selection criteria were biocompatibility, bioadhesion properties, ability to induce differentiation of fibroblasts into myofibroblasts and mechanical characterization, considering that of skin in vivo. These assays led to the selection of honeycomb of polyester. CDE constructed on this biomaterial was further characterized mechanically using tensile tests. RESULTS: The results showed that mechanical features of the obtained dermal equivalent, including myofibroblasts, were similar to skin in vivo. CONCLUSION: The original model of dermal equivalent presented herein may be a useful tool for clinical use and as an in vitro model for toxicological/pharmacological research. PMID- 22093094 TI - Computed tomography myelographic findings in dogs with cervical spondylomyelopathy. AB - Computed tomography (CT) myelography is used occasionally in the diagnosis of cervical spondylomyelopathy, but the type of lesion found in large- versus giant breed dogs using this modality has not been characterized. Our purpose was to report the frequency of compressive lesions in large- and giant-breed dogs with cervical spondylomyelopathy and imaged using CT myelography. Fifty-eight dogs were retrospectively studied, 23 large-breed and 35 giant-breed dogs. Multiple sites of compression were found in 12 large-breed dogs (52.2%) compared to 30 (85.8%) giant-breed dogs. The main site of compression was at C5-6 and C6-7 in both large-breed (91.3%) and giant-breed (72.4%) dogs. The main cause and direction of compression was disc-associated and ventral in 19 (82.6%) of the large-breed dogs while osseous changes were the primary cause of compression in 27 (77.2%) of the giant-breed dogs, with most compressions being lateral (51.4%), followed by dorsolateral (14.2%). Osseous compression was observed at C7-T1 in eight giant-breed dogs (22.8%), and at T1-T2 or T2 only in five dogs (14.3%). Four of 23 large-breed dogs (17.4%), and seven (20%) of 35 giant-breed dogs had spinal cord atrophy. Therefore, giant-breed dogs often have multiple compressions, usually caused by osseous changes causing lateralized compressions. In large-breed dogs most compressions are disc-associated and located ventrally. Considering the number of giant-breed dogs with compressions at C7-T1, T1-2, and T2, it is important to include the cranial thoracic region when imaging dogs suspected of having cervical spondylomyelopathy. PMID- 22093095 TI - Effect of GDF-5 and BMP-2 on the expression of tendo/ligamentogenesis-related markers in human PDL-derived cells. AB - OBJECTIVES: The effect of growth differentiation factor 5 and bone morphogenetic protein 2 on human periodontal ligament-derived cells was investigated with special reference to tendo/ligamentogenesis-related markers. MATERIALS AND METHODS: Effects of each factor were analyzed by quantitative PCR for scleraxis and tenomodulin and by western blotting for scleraxis. After exposure to those factors, STRO-1-positive and STRO-1-negative fractions of human periodontal ligament tissues were isolated with an immunomagnetic cell sorting system, and the expression of scleraxis in each fraction was analyzed by western blotting. Non-separated crude cells were used as a control. RESULTS: Growth differentiation factor 5 and bone morphogenetic protein 2 did not increase alkaline phosphatase activity in crude periodontal ligament-derived cells. Growth differentiation factor 5, but not bone morphogenetic protein 2, increased the expression of scleraxis in crude, STRO-1-positive and STRO-1-negative periodontal ligament derived cells. The expression of scleraxis in STRO-1-positive periodontal ligament-derived cells was significantly less compared to that in crude P2 and STRO-1-negative periodontal ligament-derived cells. CONCLUSION: Growth differentiation factor 5 induced the expression of scleraxis and may enhance tendo/ligamentogenesis in human periodontal ligament-derived cells. The expression of scleraxis was higher in STRO-1-negative fraction, suggesting more differentiated state of the cells. PMID- 22093096 TI - Comparison of the efficacy of intralesional triamcinolone acetonide and 5 fluorouracil tattooing for the treatment of keloids. AB - BACKGROUND: Hypertrophic scars and keloids may complicate wound healing secondary to trauma or surgery. A variety of treatment regimens have been used for treatment of keloids. OBJECTIVE: To compare 5-fluorouracil (5-FU) tattooing and intralesional steroid for treatment of keloids. METHODS: In this 44-week, double blind, clinical trial, 40 patients were randomized into two study groups. Patients in group 1 were given intralesional triamcinolone acetonide (TAC), and patients in group 2 were treated with 5-FU tattooing; both groups received treatment every 4 weeks for 12 weeks. Lesions were assessed for erythema, pruritus, height, surface, and induration at baseline (initiation of treatment) and at weeks 4, 8, 12, 20, 28, 36, and 44. All patients had complete blood count, liver function tests, and renal function tests before treatment and at week 20. RESULTS: All the patients completed the study. At the 44-week follow-up visits, both groups showed improvement in all parameters, but improvement was more significant in the 5-FU group (p < .05). No side effect was detected in either of the groups. CONCLUSION: 5-FU tattooing was more effective than intralesional TAC for the treatment of keloids. PMID- 22093097 TI - Notch1 promotes glioma cell migration and invasion by stimulating beta-catenin and NF-kappaB signaling via AKT activation. AB - The Notch signaling pathway has been implicated in both developmental processes and tumorigenesis. Aberrant Notch signaling has been repeatedly demonstrated to facilitate the proliferation and survival of glioma cells by regulating downstream effectors or other signaling pathways. In glioblastoma multiforme specimens from 59 patients, Notch1 was highly expressed in tumor tissues compared with normal brain tissues, and this expression was correlated with elevated AKT phosphorylation and Snail expression. Increased nuclear localization of beta catenin and p50 as well as enhanced IKKalpha/AKT interaction were also observed in glioma tissues. In U87MG cells, the activation of Notch1 by DLL4 stimulation or by the overexpression of Notch intracellular domain (NICD) resulted in AKT activation and thereby promoted beta-catenin activity and NF-kappaB signaling. Inhibition of EGFR partially blocked the beta-catenin and NF-kappaB signaling stimulated by Notch1 activation. Furthermore, NICD overexpression in U87MG cells led to the upregulated expression of several metastasis-associated molecules, which could be abrogated by the knockdown of either beta-catenin or p50. In U87MG and U251 cells, DLL4-induced cellular migration and invasion could be inhibited by either beta-catenin or a p50 inhibitor. Collectively, these results indicate that Notch activation could stimulate beta-catenin and NF-kappaB signaling through AKT activation in glioma cells. Thus, Notch activation-stimulated beta catenin and NF-kappaB signaling synergistically promote the migratory and invasive properties of glioma cells. PMID- 22093098 TI - What is your diagnosis? Lingual mass in a dog. PMID- 22093099 TI - Current methods employed in the prevention and minimization of surgical scars. AB - BACKGROUND: Postsurgical scars are of significant concern to patients and surgeons. Many studies have focused on different treatment options for established surgical scars. The prevention and minimization of such aberrant healing responses is more likely to yield better outcomes and require less time and expense. OBJECTIVE AND METHOD: A review of the literature on various forms of prophylactic treatments intended to prevent or minimize the development of prominent postsurgical scars was performed using the Pubmed database over a period from 1987 to 2010. Search terms included "scar prevention," "scar minimization," "post-surgical scar management," and "surgical scars." RESULTS: Various over-the-counter topical products commonly used by patients have failed to demonstrate any significant benefits in improving final scar outcomes. Numerous interventions performed around the time of surgery, including botulinum toxin, lasers, and intradermal injectable products, have shown effectiveness in minimizing eventual scar appearance. CONCLUSIONS: Patient education on proper wound care is a simple method of improving the cosmetic appearance of surgical scars. At the other end of the spectrum, our knowledge of the complex mechanisms of wound healing has allowed for the development of new, effective treatment modalities, including lasers, botulinum toxin, cytokines, and stem cells. PMID- 22093100 TI - Cryptococcus neoformans Ca(2+) homeostasis requires a chloride channel/antiporter Clc1 in JEC21, but not in H99. AB - CLC-type chloride/proton antiporters are required for copper/iron homeostasis in fungi. A relationship between CLCs and Ca(2+) homeostasis has not been found before. Here we demonstrate the requirement of the antiporter CLC1 for Ca(2+) homeostasis/signaling in Cryptococcus neoformans. The deletion of CLC1 in JEC21 resulted in a mutant hypersensitive to cyclosporine A, an inhibitor of calcineurin. Intracellular Ca(2+) deficiency in the mutant Tx1 was confirmed with Fluo-3 staining epi-fluorescence microscopy. Tx1 failed to grow at elevated temperature and in SDS and displayed defects in cell wall integrity and cell separation. This defective phenotype is because of Ca(2+) deficiency that was restorable by exogenous Ca(2+) . In contrast, H99 CLC1 was dispensable for Ca(2+) homeostasis and had no comparable defective consequences if deleted, suggesting divergent roles of CLCs in Ca(2+) homeostasis. Distinct Ca(2+) homeostasis mechanisms may contribute the virulence difference between the two strains. This work reveals a novel action of CLC antiporters in fungi and may provide information as to the evolution of pathogenicity among cryptococcal strains. PMID- 22093102 TI - Desktop microsimulation: a tool to improve efficiency in the medical office practice. AB - Because the economic crisis in the United States continues to have an impact on healthcare organizations, industry leaders must optimize their decision making. Discrete-event computer simulation is a quality tool with a demonstrated track record of improving the precision of analysis for process redesign. However, the use of simulation to consolidate practices and design efficiencies into an unfinished medical office building was a unique task. A discrete-event computer simulation package was used to model the operations and forecast future results for four orthopedic surgery practices. The scenarios were created to allow an evaluation of the impact of process change on the output variables of exam room utilization, patient queue size, and staff utilization. The model helped with decisions regarding space allocation and efficient exam room use by demonstrating the impact of process changes in patient queues at check-in/out, x-ray, and cast room locations when compared to the status quo model. The analysis impacted decisions on facility layout, patient flow, and staff functions in this newly consolidated practice. Simulation was found to be a useful tool for process redesign and decision making even prior to building occupancy. PMID- 22093101 TI - A protective role for periostin and TGF-beta in IgE-mediated allergy and airway hyperresponsiveness. AB - BACKGROUND: The pathophysiology of asthma involves allergic inflammation and remodelling in the airway and airway hyperresponsiveness (AHR) to cholinergic stimuli, but many details of the specific underlying cellular and molecular mechanisms remain unknown. Periostin is a matricellular protein with roles in tissue repair following injury in both the skin and heart. It has recently been shown to be up-regulated in the airway epithelium of asthmatics and to increase active TGF-beta. Though one might expect periostin to play a deleterious role in asthma pathogenesis, to date its biological role in the airway is unknown. OBJECTIVE: To determine the effect of periostin deficiency on airway responses to inhaled allergen. METHODS: In vivo measures of airway responsiveness, inflammation, and remodelling were made in periostin deficient mice and wild-type controls following repeated intranasal challenge with Aspergillus fumigatus antigen. In vitro studies of the effects of epithelial cell-derived periostin on murine T cells were also performed. RESULTS: Surprisingly, compared with wild type controls, periostin deficient mice developed increased AHR and serum IgE levels following allergen challenge without differences in two outcomes of airway remodelling (mucus metaplasia and peribronchial fibrosis). These changes were associated with decreased expression of TGF-beta1 and Foxp3 in the lungs of periostin deficient mice. Airway epithelial cell-derived periostin-induced conversion of CD4(+) CD25(-) cells into CD25(+) , Foxp3(+) T cells in vitro in a TGF-beta dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE: Allergen-induced increases in serum IgE and bronchial hyperresponsiveness are exaggerated in periostin deficient mice challenged with inhaled aeroallergen. The mechanism of periostin's effect as a brake on allergen-induced responses may involve augmentation of TGF-beta-induced T regulatory cell differentiation. PMID- 22093103 TI - Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in solid organ transplantation. AB - Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is spreading globally and represents a challenge in infection control and treatment. Solid organ transplant (SOT) recipients are especially at risk for infection by multidrug-resistant bacteria, and little is known about infection with KPC producing organisms in this setting. The aim of this study was to describe the clinical and microbiologic aspects of KPC-producing K. pneumoniae infections in SOT recipients. A KPC-2-producing K. pneumoniae outbreak was identified in a public teaching tertiary care hospital in Sao Paulo, Brazil, in June 2009. During the outbreak, cases of KPC-2-producing K. pneumoniae infection in SOT recipients occurred between July 2009 and February 2010; these cases were retrospectively reviewed. Overall, 12 episodes of infection with KPC-producing K. pneumoniae occurred in 2 heart, 4 liver, and 6 kidney transplant recipients with incidence rates of 16.7%, 12.9%, and 26.3% in heart, liver, and kidney transplantation, respectively. Infection occurred at a median time of 20 days after transplantation. Primary infection sites were as follows: 4 urinary tract infections, 4 bloodstream infections, 2 pneumonias, and 2 surgical site infections. All patients except one had received antibiotics in the last 30 days, mostly piperacillin-tazobactam or glycopeptides. All strains exhibited susceptibility to amikacin and gentamicin. Patients were treated with tigecycline plus polymyxin B (3 cases), polymyxin B plus carbapenem (3 cases), polymyxin B alone (3 cases), or tigecycline plus imipenem (1 case). In 2 cases, patients received only carbapenem, and death occurred before the final culture result. The overall 30-day mortality rate was 42%. In this series of KPC-producing K. pneumoniae infection in SOT recipients, the infection occurrence was high during an institutional outbreak and was potentially life threatening. PMID- 22093104 TI - Pattern and rate of progression of periodontal attachment loss in an urban population of South Brazil: a 5-years population-based prospective study. AB - AIM: The aim of this 5-years longitudinal study was to investigate the pattern and rate of periodontal attachment loss (PAL) progression in an urban population in South Brazil. METHODS: In 2001, a multistage probability sampling strategy was used to derive a representative sample of 1,465 dentate individuals from Porto Alegre, Brazil. Five years later, 697 dentate individuals (294M/403F, mean age: 37.9 +/- 13.3) were available for follow-up. PAL was assessed by calibrated examiners using a full-mouth protocol. Estimates of proximal PAL progression and standard errors (SE) are reported. RESULTS: Fifty-six per cent (SE: 1.9) and 36% (SE: 1.8) of subjects showed PAL progression >=3 mm affecting >=2 and >=4 teeth respectively. PAL progression >=3 mm was mostly localized affecting 3.8 (SE: 0.2) teeth and 5.7 (SE: 0.3) sites. Annual PAL progression was, on average, 0.3 mm (SE: 0.01). Significant differences in PAL progression were observed according to age, gender, race and socioeconomic status. PAL progression increased with age reaching the highest progression rate in the 40-49 years cohort, and then decreased in older age groups. PAL progression was consistently higher among males and non-Whites than females and whites. CONCLUSION: A large proportion of this urban Brazilian sample was affected by PAL progression underscoring the need for health promotion initiatives aiming at preventing progression of destructive periodontal disease. PMID- 22093105 TI - Rising concern over cosmetic tattoos. AB - BACKGROUND: A rise in popularity of cosmetic tattoos has led to an increase in adverse reactions. Due to more pressing concerns, the Food and Drug Administration (FDA) has not traditionally enforced its authority over tattoo inks. OBJECTIVE: To raise awareness of the dangers of cosmetic tattoos. MATERIALS AND METHODS: We reviewed FDA policies regarding tattoo ink, different ink components, adverse reactions, and various treatment options for cosmetic tattoo removal. RESULTS AND CONCLUSION: An increase in consumer complaints has prompted FDA investigation into tattoo inks and their safety. It is important that further complications be reported to the FDA to promote regulation of cosmetic tattoo inks. PMID- 22093106 TI - Use of a gentamicin-impregnated collagen sheet (Collatamp((r)) ) following implantation of a sacral nerve stimulator for faecal incontinence. AB - AIM: Gentamicin-impregnated collagen (Collatamp((r)) ) is well described for the prevention of infection in surgery. This technical note describes its intraoperative use as a prophylactic measure to prevent infection following implantation of a sacral nerve stimulator for faecal incontinence. METHOD: Following implantation of the Interstim II Neurostimulator (Medtronic Neuromodulation, 710 Medtronic Parkway, Minneapolis, USA) in a subcutaneous pocket overlying the gluteal muscle, a single sheet of 10cm * 10cm gentamicin impregnated collagen is placed within the wound covering the implant. The subcutaneous tissue and skin are then closed in separate layers. RESULTS: To date eight patients [median age 46.5 (30-59) years] have received prophylactic cover with gentamicin-impregnated collagen following permanent sacral nerve stimulator implantation. At a median interval of 89.5 (51-128) days, none of these patients developed a wound infection at the site of the neurostimulator implant. CONCLUSION: Gentamicin-impregnated collagen (Collatamp((r)) ) used in the implantation of a sacral nerve stimulator may be a useful addition to the technique. PMID- 22093107 TI - Dopamine D3 receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression. AB - Dysfunction of dopamine D3 receptors, particularly in the mesocorticolimbic system, has been linked to the pathogenesis of major depression. Preclinical data show enhanced D3 receptor binding in the striatum upon antidepressant medication and electroconvulsive therapy (ECT). Thus, the potential impact of dopamine D3 receptor gene (DRD3) variation on ECT outcome in treatment-resistant major depression was evaluated by applying a combined molecular and imaging genetic approach. Altogether, 10 representative variants covering 95.4% of DRD3 gene variation were investigated for association with response to ECT in a sample of 104 (71 female, 33 male) Caucasian patients with pharmacorefractory major depression. Additionally, ventral striatum responsiveness to happy faces was assessed in two independent samples of depressed patients (total N=54) by means of functional magnetic resonance imaging at 3 T. Significant association of DRD3 rs3732790, rs3773679 and rs9817063 variants with response (uncorrected p=0.02 0.03) and remission (uncorrected p=0.01) after ECT was discerned. Logistic regression analyses revealed association of rs3732790 (uncorrected p=0.009; corrected p=0.045) and rs3773679 (uncorrected p=0.009; corrected p=0.045) with remission when applying a recessive model of inheritance. The rs3732790T allele conferring a more favourable treatment response was furthermore found to be associated with stronger striatal responsiveness to happy facial expressions (sample 1: cluster-corrected p=0.002; sample 2: p=0.023). In summary, the present study suggests some impact of DRD3 gene variation on ECT response, potentially mediated by alteration of striatal engagement during the processing of emotionally rewarding stimuli. PMID- 22093108 TI - Unilateral positive biopsies in low risk prostate cancer patients diagnosed with extended transrectal ultrasound-guided biopsy schemes do not predict unilateral prostate cancer at radical prostatectomy. AB - Focal therapy is an emergent therapeutic option for prostate cancer. Focal therapy includes a variety of therapeutic approaches ranging from lesion treatment to sub-total gland treatment. In this context, an accurate selection of patients having unilateral prostate cancer is closely related to the success of these strategies, especially when a hemi-ablative approach is considered. As prostate cancer is often multifocal, the critical issue is whether it is possible to preoperatively predict a clinically significant unifocal and/or unilateral lesion with sufficient accuracy to recommend focal or hemi-ablative therapy, relying on clinical characteristics and pathological data derived from the biopsy. Our study clearly demonstrates that the prediction of unilateral prostate cancer is not accurate, based on preoperative variables (predictive accuracy 52.3%). Our study is the first study based on an extended biopsy template. Even in patients diagnosed with extended biopsy, the accuracy of the available predictors is far from the ideal prediction. To date, there is no way of correctly identifying patients who will harbour unilateral prostate cancer based on routinely available variables. OBJECTIVE: o establish the predictors of unilateral prostate cancer in a population of patients with low risk prostate cancer, diagnosed with extended biopsy and submitted to radical prostatectomy, potentially candidates for focal therapy. PATIENTS AND METHODS: The study included 321 consecutive patients with low risk (clinical stage T1, Gleason score 3 + 3 or less, prostate-specific antigen [PSA] < 10 ng/mL) unilateral prostate cancer diagnosed after extended biopsy who were subsequently treated with radical prostatectomy between 2002 and 2009 at a single institution. We evaluated the rate of unilateral prostate cancers at final pathology following radical prostatectomy, defined as pT2a or pT2b stage. Univariable and multivariable logistic regression analyses were used to identify predictors of unilateral prostate cancers. Predictive accuracy was assessed with estimates of the area under the receiver operating characteristic curve, which were subjected to 200 bootstraps to reduce overfit bias. RESULTS: At final pathology only 29.3% patients harboured unilateral prostate cancer. No significant differences in terms of age, preoperative PSA, prostate volume and percentage of positive cores were recorded between patients with unilateral prostate cancer and patients with more advanced stage (all P >= 0.07). Patients harbouring unilateral prostate cancer had a smaller number of positive biopsy cores (2.8 vs 3.2, P = 0.056) compared with patients with stage pT2c or higher at final pathology. Patients with unilateral prostate cancer had a higher rate of Gleason sum 6 compared with patients with more advanced pathological stage (pT2c or higher: 85.1% vs 65.6%; P = 0.002). On multivariable analyses, only the percentage of positive cores (odds ratio 0.57; P = 0.047) was an independent predictor of unilateral prostate cancer at radical prostatectomy, after controlling for age, PSA at diagnosis and prostate volume (all P >= 0.3). The newly developed model for identifying the presence of unilateral prostate cancer failed to achieve accurate prediction (area under the curve 52.3%). When only patients with a single positive core were considered, no differences in PSA and prostate volume were detected (all P >= 0.5) and a similar rate of unilateral prostate cancer was demonstrated (33.3% vs 28.4%; P = 0.5). CONCLUSIONS: In patients with unilateral low risk prostate cancer at biopsy, only one-third showed unilateral prostate cancer at radical prostatectomy. The number of cores and the number of positive cores represented independent predictors of unilateral prostate cancer. However, the accuracy of the multivariable model in predicting unilateral prostate cancer is low (52.3%), thus making prediction of unilateral prostate cancer extremely inaccurate. These results need to be taken into account in those cases where focal therapy is considered as a treatment of prostate cancer. PMID- 22093109 TI - Intestinal defensin secretion in infancy is associated with the emergence of sensitization and atopic dermatitis. AB - BACKGROUND: Intestinal flora and innate immunity, and their interactions impact adaptive immunity. OBJECTIVE: To study the association of fecal defensin levels in infancy with synbiotic treatment and with the emergence of atopy. METHODS: The randomly selected group of 102 infants belonged to a randomized, double-blind placebo-controlled trial where 1223 infants in high risk for allergy received, from birth to 6 months, a mixture of synbiotics, or placebo. Clinical trials registration number for the clinical trial is NCT00298337. In the subgroup, 45 received active treatment and 56 received placebo treatment. Follow-up for the emergence of sensitization and allergic diseases lasted 5 years. At the age of 3 (n = 96) and 6 (n = 87) months, we measured fecal levels of human neutrophil peptide (HNP) 1-3 and of beta-defensin 2 (HBD2) using enzyme linked immunosorbent assays and concentrations of lactic acid bacteria on MRS agar. We used multifactorial regression in data analysis. RESULTS: Fecal levels of HNP1-3 and HBD2 decreased from the age of 3-6 months (P < 0.0001). HBD2 levels decreased less in the synbiotics group compared with placebo (P < 0.02). High fecal HBD2 levels at 6 months were associated with an increased risk for sensitization by the age of 5 years (OR 2.5, 95% confidence interval 1.1-5.8, P < 0.03). High fecal HNP1-3 levels at 6 months were associated with a decreased risk for atopic dermatitis (OR 0.4, 95% CI 0.1-1.0, P < 0.05). Samples with very low or high HBD2 levels at 6 months had low concentrations of lactic acid bacteria (P < 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Early innate immunity responses in the gut are associated with the emergence of sensitization and atopic dermatitis later in childhood. PMID- 22093110 TI - Effects of fluorides on apoptosis and activation of human umbilical vein endothelial cells. AB - OBJECTIVE: To determine the effects of fluorides on endothelial functioning. MATERIALS AND METHODS: We analyzed expressions of adhesion molecules, ICAM-1 and ICAM-3, and annexin V, on the surface of human umbilical vein endothelial cells (HUVECs) exposed to various concentrations of NaF and SnF(2) . We compared the effects of fluoride-induced changes with those obtained when stimulating HUVECs with TNF-alpha and verified whether N-acetyl cysteine (NAC), well-known antioxidant, can prevent both fluoride- and TNF-alpha-induced alterations. RESULTS: The expressions of annexin V and ICAM-1 increased significantly after adding NaF (5.0 or 7.5mM) or Sn(2) F (0.5 or 0.75mM) to the culture medium. Pre incubating HUVECs with NAC prevented the effects induced by 5.0 mM of NaF and 0.5 mM of Sn(2) F. Only the highest concentration of NaF (7.5mM) triggered the expression of ICAM-3. The expressions of all three molecules increased significantly upon stimulating the cultures with TNF-alpha (20ng ml(-1) ); these changes were not reversed by pre-incubation with NAC. CONCLUSIONS: Fluorides induce oxidative stress, resulting in apoptosis and activation of HUVECs, manifested by an elevated expression of ICAM-1. The oxidative stress resulting from a stimulation by the highest NaF concentration triggers ICAM-3 expression on the HUVECs' surface. PMID- 22093111 TI - Abdominal actinomycosis masquerading as colon cancer in a liver transplant recipient. AB - Infections in transplant recipients are associated with high morbidity and mortality, making their early recognition and treatment particularly important. Abdominal actinomycosis is a rare clinical entity and difficult to diagnose because of its various and nonspecific features. We describe a 57-year-old patient who presented with abdominal actinomycosis simulating colon cancer 6 years after liver transplantation. The main symptom was abdominal pain. Abdominal computed tomography and colonoscopy revealed an intraluminal 4.5 cm mass in the right colon, raising suspicions of a colonic malignancy and leading to surgical intervention. The postoperative pathologic study showed sulfur granules in the resected specimen compatible with abdominal actinomycosis. No signs of recurrence were seen throughout the 6-month follow-up. The literature on actinomycosis infections in immune-compromised hosts is reviewed. This presentation of actinomycosis in a liver transplant recipient has not been described previously, to our knowledge. PMID- 22093112 TI - High-resolution computed tomography bronchial lumen to pulmonary artery diameter ratio in anesthetized ventilated cats with normal lungs. AB - High-resolution computed tomography (CT) is the preferred noninvasive tool for diagnosing bronchiectasis in people. A criterion for evaluating dilation of the bronchus is the bronchial lumen to pulmonary artery diameter (bronchoarterial ratio [BA ratio]). A ratio of > 1.0 in humans or > 2.0 in dogs has been suggested as a threshold for identifying bronchiectasis. The purpose of this study was to establish the BA ratio in normal cats. Fourteen specific pathogen-free cats were selected for analysis of thoracic CT images. The BA ratios of the lobar bronchi of the left cranial (cranial and caudal parts), right cranial, right middle, left caudal, and right caudal lung lobes were measured. The mean of the mean BA ratio of all lung lobes was 0.71 +/- 0.05. Individual BA ratios ranged from 0.5 to 1.11. Comparing individual lobes for each cat, there was no significant difference (P = 0.145) in mean BA ratio between lung lobes. A mean BA ratio for these normal cats was 0.71 +/- 0.1, which suggests an upper cut-off normal value > 0.91 (mean +/- 2 standard deviations) between normal and abnormal cats. PMID- 22093113 TI - What is your diagnosis? Intracranial mass in a dog. PMID- 22093114 TI - Using en face ink to guide the conservative sectioning of a Mohs margin. AB - BACKGROUND: While the epidermal rim of a Mohs layer routinely requires some manipulation, the deep margin seems to conform easily to a smooth surface for sectioning even when tissue textures and contours are prominent. How well these common features of the deep margin flatten during processing has not been well studied. OBJECTIVE: To determine how successfully tissue processing flattens the deep margin of Mohs specimens. METHODS: Using en face inking, this study compared the sectioning required to reach a completed epidermal margin with that of the completed deep margin in 100 routine first-stage Mohs specimens. RESULTS: A mean of 248.8 MUm of additional sectioning beyond the completed epidermal margin was required in 74% of specimens to reach the completed deep margin. This deep margin differential was associated with increasing layer size (p = .003) and those specimens that required the least amount of sectioning to reach a completed epidermal margin (p < .001). CONCLUSIONS: The differential between the epidermal and deep margin suggests that tissue texture and contour irregularities can be easily compressed and internalized during embedding. En face inking can be used to delineate the tissue texture and surgical features of a Mohs margin ensuring a complete and conservative section evaluation. PMID- 22093115 TI - Lateral longitudinal excision of the nail unit. PMID- 22093116 TI - Treatment of IBS-D with 5-HT3 receptor antagonists vs spasmolytic agents: similar therapeutical effects from heterogeneous pharmacological targets. AB - There is still no agreement over optimal pharmacological treatment for irritable bowel syndrome (IBS). Patients with IBS and diarrhea (IBS-D) demonstrate both visceral hypersensitivity and impaired colonic motility with increased frequency and amplitude of giant migrating contractions (GMCs) which cause mass movements, propulsion of stools and initiation of defecation. Both antispasmodics and 5-HT3 receptor antagonists can improve the symptoms and the impaired colonic motility of patients with IBS-D though through very different mechanisms. Antispasmodics act by directly relaxing the colonic smooth muscle cells or antagonizing the excitatory neuromuscular neurotransmission. In contrast, the mechanism of action of 5HT3 antagonists is much more complex and subtle as they inhibit the ascending excitatory component of the peristaltic reflex and GMCs. There are some concerns about the safety of 5HT3 antagonists in long-term treatment. Most of the studies on the treatment of IBS have followed the pharmacological strategy of looking for big clinical effects acting on a single receptor/target. We propose a pharmacologic strategy which uses different drugs for pain and dysmotility in the same patient and includes specific drugs acting on smooth muscle cells, neuromuscular transmission, synaptic transmission and intrinsic afferents. The clinical effect on IBS symptoms would be found in the sum of all these smaller effects on multiple targets. PMID- 22093117 TI - Pain education for physiotherapists: is it time for curriculum reform? PMID- 22093118 TI - Engagement of physiotherapists in cardiology research. PMID- 22093119 TI - Inspiratory muscle training increases inspiratory muscle strength in patients weaning from mechanical ventilation: a systematic review. AB - QUESTION: Does inspiratory muscle training improve inspiratory muscle strength and endurance, facilitate weaning, improve survival, and reduce the rate of reintubation and tracheostomy in adults receiving mechanical ventilation? DESIGN: Systematic review of randomised or quasi-randomised controlled trials. PARTICIPANTS: Adults over 16 years of age receiving mechanical ventilation. INTERVENTION: Inspiratory muscle training versus sham or no inspiratory muscle training. OUTCOME MEASURES: Data were extracted regarding inspiratory muscle strength and endurance, the duration of unassisted breathing periods, weaning success and duration, reintubation and tracheostomy, survival, adverse effects, and length of stay. RESULTS: Three studies involving 150 participants were included in the review. The studies varied in time to commencement of the training, the device used, the training protocol, and the outcomes measured. Inspiratory muscle training significantly increased inspiratory muscle strength over sham or no training (weighted mean difference 8 cmH(2)O, 95% CI 6 to 9). There were no statistically significant differences between the groups in weaning success or duration, survival, reintubation, or tracheostomy. CONCLUSION: Inspiratory muscle training was found to significantly increase inspiratory muscle strength in adults undergoing mechanical ventilation. Despite data from a substantial pooled cohort, it is not yet clear whether the increase in inspiratory muscle strength leads to a shorter duration of mechanical ventilation, improved weaning success, or improved survival. Further large randomised studies are required to clarify the impact of inspiratory muscle training on patients receiving mechanical ventilation. REVIEW REGISTRATION: PROSPERO CRD42011001132. PMID- 22093120 TI - Timing of dornase alpha inhalation does not affect the efficacy of an airway clearance regimen in adults with cystic fibrosis: a randomised crossover trial. AB - QUESTION: Does the timing of inhalation of dornase alpha in relation to physical airway clearance techniques influence the effect of the entire airway clearance regimen?. DESIGN: A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinding of patients, therapists, and assessors. PARTICIPANTS: Twenty adults with cystic fibrosis who were not taking dornase alpha were recruited, of whom 17 were randomised and completed the trial. INTERVENTION: Participants performed an individually tailored session of physical airway clearance techniques for at least 15 minutes per day for 28 days. For 14 days, dornase alpha was inhaled before each session of airway clearance techniques and a placebo was inhaled after. For the other 14 days, placebo was inhaled before and dornase alpha after airway clearance techniques. The order of the two 14-day periods was randomised. OUTCOME MEASURES: The primary outcome was the forced expiratory volume in 1 sec (FEV(1)). Secondary outcomes were forced vital capacity, 24-hour sputum production, sputum production during the airway clearance regimen, oxygen saturation, peak oxygen consumption during an incremental exercise test, oxygen desaturation during exercise, and quality of life. RESULTS: Inhalation of dornase alpha after airway clearance techniques did not significantly affect the change in FEV(1) compared with inhalation before airway clearance techniques, mean difference 0.04 L, 95% CI -0.14 to 0.23. None of the secondary outcomes differed significantly between the study arms. There was good correlation between the change in FEV(1) and the change in quality of life scores. CONCLUSION: Timing of dornase alpha can be selected according to convenience, patient preference, or to accommodate the timing of other medications in the treatment regimen. TRIAL REGISTRATION: ACTRN12611001041943. PMID- 22093121 TI - Telephone coaching can increase activity levels for people with non-chronic low back pain: a randomised trial. AB - QUESTION: Does the addition of telephone coaching to usual physiotherapy care improve activity for people with non-chronic low back pain and low to moderate recovery expectations? DESIGN: Randomised trial with concealed allocation and intention-to-treat analysis. PARTICIPANTS: People attending the physiotherapy department of a public hospital for treatment within eight weeks of onset of non specific low back pain. Eligible participants had low to moderate recovery expectations, defined as a response of 7 or less to the question 'How certain are you that you will return to all of your usual activities one month from today?' on a scale from 0 (not certain at all) to 10 (completely certain). INTERVENTION: Five sessions of telephone coaching by a physiotherapist trained in health coaching techniques in addition to usual physiotherapy compared to usual physiotherapy alone. OUTCOME MEASURES: The Patient Specific Functional Scale, Oswestry Disability Index, Pain Self Efficacy Questionnaire, and recovery expectation were measured at baseline, 4, and 12 weeks. RESULTS: 30 participants were recruited, with 26 completing all measures at 12 weeks. There were no significant differences between groups at 4 weeks. After 12 weeks the coaching group improved significantly more than the control group on two 10-point scales: the Patient Specific Functional Scale (mean difference 3.0 points, 95% CI 0.7 to 5.4) and recovery expectation (mean difference 3.4 points, 95% CI 1.1 to 5.7). Estimates of effect sizes were moderate to large in favour of the intervention. CONCLUSION: The addition of telephone health coaching to usual physiotherapy care for people with non-chronic non-specific low back pain led to clinically important improvements in activity and recovery expectation. TRIAL REGISTRATION: ACTRN12607000458437. PMID- 22093122 TI - The Assessment of Physiotherapy Practice (APP) is a valid measure of professional competence of physiotherapy students: a cross-sectional study with Rasch analysis. AB - QUESTION: Is the Assessment of Physiotherapy Practice (APP) a valid instrument for the assessment of entry-level competence in physiotherapy students? DESIGN: Cross-sectional study with Rasch analysis of initial (n=326) and validation samples (n=318). Students were assessed on completion of 4, 5, or 6-week clinical placements across one university semester. PARTICIPANTS: 298 clinical educators and 456 physiotherapy students at nine universities in Australia and New Zealand provided 644 completed APP instruments. RESULTS: APP data in both samples showed overall fit to a Rasch model of expected item functioning for interval scale measurement. Item 6 (Written communication) exhibited misfit in both samples, but was retained as an important element of competence. The hierarchy of item difficulty was the same in both samples with items related to professional behaviour and communication the easiest to achieve and items related to clinical reasoning the most difficult. Item difficulty was well targeted to person ability. No Differential Item Functioning was identified, indicating that the scale performed in a comparable way regardless of the student's age, gender or amount of prior clinical experience, and the educator's age, gender, or experience as an educator, or the type of facility, university, or clinical area. The instrument demonstrated unidimensionality confirming the appropriateness of summing the scale scores on each item to provide an overall score of clinical competence and was able to discriminate four levels of professional competence (Person Separation Index=0.96). Person ability and raw APP scores had a linear relationship (r(2)=0.99). CONCLUSION: Rasch analysis supports the interpretation that a student's APP score is an indication of their underlying level of professional competence in workplace practice. PMID- 22093123 TI - Provocative wrist tests and MRI are of limited diagnostic value for suspected wrist ligament injuries: a cross-sectional study. AB - QUESTION: What is the diagnostic value of provocative wrist tests and magnetic resonance imaging (MRI) for suspected wrist ligament injuries? DESIGN: Cross sectional study. PARTICIPANTS: 105 people presenting to hand clinics with wrist pain and suspected wrist ligament injuries were evaluated prospectively. OUTCOME MEASURES: The integrity of wrist ligaments was tested with seven provocative tests. The results were compared to the reference standard of arthroscopy. In a subgroup of 55 participants, MRI findings were also compared to arthroscopy. The provocative tests were the scaphoid shift test (SS test), lunotriquetral test (LT test), midcarpal test (MC test), distal radioulnar joint test (DRUJ test), triangular fibrocartilage complex (TFCC) stress test (TFCC test), TFCC stress test with compression (TFCC comp test), and the gripping rotatory impaction test (GRIT). RESULTS: Most provocative tests and MRI findings were of little or no value for diagnosing wrist ligament injuries. Exceptions were the SS test (+ve LR 2.88 and -ve LR 0.28), MC test (+ve LR 2.67) and DRUJ test (-ve LR 0.30), all of which were of mild diagnostic usefulness. MRI was moderately useful for diagnosing TFCC injuries (+ve LR 5.56, -ve LR 0.15), and was mildly useful for diagnosing scapholunate (SL) ligament injuries (+ve LR 4.17, -ve LR 0.32) and lunate cartilage damage (+ve LR 3.67, -ve LR 0.33). Adding MRI to provocative tests improved the accuracy of diagnosis of TFCC injuries slightly (by 13%) and lunate cartilage damage (by 8%). CONCLUSION: Provocative wrist tests of SL ligament injuries and midcarpal ligament injuries are mildly useful for diagnosing wrist injuries. MRI diagnostic findings of SL ligament injuries, lunate cartilage damage, and TFCC are mildly to moderately useful. MRI slightly improves the diagnosis of TFCC injury and lunate cartilage damage compared to provocative tests alone. PMID- 22093124 TI - Aerobic exercise enhances executive function and academic achievement in sedentary, overweight children aged 7-11 years. AB - Summary of: Davis CL et al (2011) Exercise improves executive function and achievement and alters brain activation in overweight children: a randomized controlled trial. Health Pscyh 30: 91-98. [Prepared by Nora Shields, CAP Editor.] QUESTION: Does aerobic exercise improve cognition and academic achievement in overweight children aged 7-11 years? DESIGN: Randomised, controlled trial with concealed allocation and blinded outcome assessment. SETTING: After school program in the United States. PARTICIPANTS: Overweight, inactive children aged 7 11 years with no medical contraindication to exercise. Randomisation of 171 participants allocated 56 to a high dose exercise group, 55 to a low dose exercise group, and 60 to a control group. INTERVENTIONS: Both exercise groups were transported to an after school exercise program each school day and participated in aerobic activities including running games, jump rope, and modified basketball and soccer. The emphasis was on intensity, enjoyment, and safety, not competition or skill enhancement. The student-instructor ratio was 9:1. Heart rate monitors were used to observe the exercise intensity. Points were awarded for maintaining an average of>150 beats per minute and could be redeemed for weekly prizes. The high dose exercise group received 40 min/day aerobic exercise and the low dose exercise group received 20 min/day aerobic exercise and 20 min/day unsupervised sedentary activities including board games, drawing, and card games. The average duration of the program was 13 +/- 1.6 weeks. The control group did not receive any after school program or transportation. OUTCOME MEASURES: The primary outcome was the Cognitive Assessment System taken at baseline and postintervention. This measure tests four cognitive processes: planning (or executive function), attention, simultaneous, and successive tasks with each process yielding a standard score with a mean of 100 and a SD of 15. Secondary outcome measures were the broad reading and mathematics clusters of the Woodcock-Johnson Tests of Achievement III. RESULTS: 164 participants completed the study. At the end of the intervention period, there was a dose-response benefit of exercise on executive function (linear trend p=0.013) and mathematics achievement (linear trend p=0.045); ie, the post-intervention group scores for these outcomes increased with the intensity of exercise. Compared to the control group, exposure to either exercise program resulted in higher executive function scores (mean difference=-2.8, 95% CI -5.3 to -0.2 points) but not in higher mathematics achievement scores. The groups did not differ significantly on any of the other outcomes. There were no differences between the two exercise groups. CONCLUSION: Aerobic exercise enhances executive function in overweight children. Executive function develops in childhood and is important for adaptive behaviour and cognitive development. PMID- 22093125 TI - Questioning the role of targeted respiratory physiotherapy over and above a standard clinical pathway in the postoperative management of patients following open thoracotomy. AB - Summary of: Reeve JC et al (2010) Does physiotherapy reduce the incidence of postoperative pulmonary complications following pulmonary resection via open thoracotomy? A preliminary randomised single-blind clinical trial. Eur J Cardiothorac Surg 37: 1158-1166. [Prepared by Kylie Hill, CAP Editor.] QUESTION: Does routine prophylactic targeted respiratory physiotherapy after elective pulmonary resection via open thoracotomy decrease the incidence of postoperative pulmonary complications and reduce length of hospital stay? DESIGN: Randomised, controlled trial with concealed allocation in which those who collected outcome measures were blinded to group allocation. SETTING: Hospital ward of a tertiary referral centre in Auckland, New Zealand. PARTICIPANTS: Adults scheduled for pulmonary resection via open thoracotomy. EXCLUSION CRITERIA: (i) unable to understand written and spoken English, (ii) tumour invasion of the chest wall or brachial plexus, (iii) physiotherapy for a respiratory or shoulder problem within 2 weeks prior to admission, (iv) development of a postoperative pulmonary complication prior to randomisation on Day 1 postoperatively, or (v) intubation and mechanical ventilation >= 24 hours following surgery. Randomisation of 76 patients allocated 42 to the intervention group and 34 to the control group. INTERVENTIONS: Both groups received usual medical and nursing care via a standardised clinical pathway, which included early and frequent position changes, sitting out of bed on the first postoperative day, early ambulation and frequent pain assessment. In addition, the intervention group received daily targeted respiratory physiotherapy, which comprised deep breathing and coughing exercises, assistance with ambulation, and progressive shoulder and thoracic cage exercises. OUTCOME MEASURES: The primary outcome was incidence of postoperative pulmonary complications, defined using a standardised diagnostic tool. The secondary outcome was the length of hospital stay. RESULTS: The primary and secondary outcomes were available for all enrolled patients. Neither the incidence of postoperative pulmonary complications [mean difference intervention control 1.8% (95% CI -10.6 to 13.1%)] nor the hospital length of stay [intervention group median 6.0 days, control group median 6.0 days; p=0.87) differed significantly between groups. The overall incidence of postoperative pulmonary complications (3.9%) was lower than expected. CONCLUSION: In adults following open thoracotomy, the addition of targeted respiratory physiotherapy to a standardised clinical pathway that included early mobilisation did not reduce the incidence of postoperative pulmonary complications or change length of hospital stay. PMID- 22093126 TI - Surgery with disc prosthesis may produce better outcomes than multidisciplinary rehabilitation for patients with chronic low back pain. AB - Hellum C et al (2011) Surgery with disc prosthesis versus rehabilitation in patients with low back pain and degenerative disc: two year follow-up of randomised study. BMJ 342: d2786 doi:10.1136/bmj.d2786. [Prepared by Margreth Grotle and Kare Birger Hagen, CAP Editors.] QUESTION: What are the effects of surgery with disc prosthesis compared to multidisciplinary rehabilitation for patients with chronic low back pain? DESIGN: A single blind randomised controlled multicentre trial. SETTING: Five university hospitals in Norway. PARTICIPANTS: Men and women 25-55 years with low back pain as the main symptom for at least one year, physiotherapy or chiropractic treatment for at least six months without sufficient effect, a score of at least 30 on the Oswestry disability index, and degenerative intervertebral disc changes at L4/L5 or L5/S1, or both. Patients with nerve root involvement were excluded. Randomisation of 179 participants allocated 86 patients to surgical treatment and 87 to rehabilitation. INTERVENTIONS: Rehabilitation consisted of a cognitive approach and supervised physical exercise directed by physiotherapists and specialists in physical medicine and rehabilitation. Intervention was standardised and organised as outpatient treatment in groups; it lasted for about 60 hours over 3-5 weeks. Follow-up consultations were conducted at 6 weeks, 3 and 6 months, and 1 year after the intervention. Surgical intervention consisted of replacement of the degenerative intervertebral lumbar disc with an artificial lumbar disc. Surgeons were required to have inserted at least six disc prostheses before performing surgery in the study. Patients were not referred for postoperative physiotherapy, but at 6 weeks follow-up they could be referred for physiotherapy if required, emphasising general mobilisation and non-specific exercises. OUTCOME MEASURES: The primary outcome was the Oswestry Disability Index (ODI, 0-100 scale) at 2 years. Secondary outcomes included low back pain (0-100 VAS), SF-36, and EQ-5D scores. RESULTS: The drop-out rate at 2 years was 15% in the surgical arm and 24% in the rehabilitation arm. At 2 years follow up, the between group differences (95% CI) in favour of the surgical treatment were -8.4 (-13.2 to -3.6) for ODI, 12.2 (-21.3 to -3.1) for pain, and 5.8 (2.5 to 9.1) for SF-36 physical health summary. No differences were found in SF-36 mental health summary or EQ-5D. CONCLUSION: Surgery with disc prosthesis produced significantly greater improvement in variables measuring physical disability and pain, but the difference in ODI between groups did not exceed the pre-specified minimally important difference of 10 points, so it is unclear whether the observed changes were clinically meaningful. PMID- 22093127 TI - Manual lymph drainage when added to advice and exercise may not be effective in preventing lymphoedema after surgery for breast cancer. AB - Summary of: Devoogdt N et al (2011) Effect of manual lymph drainage in addition to guidelines and exercise therapy on arm lymphoedema related to breast cancer: randomized controlled trial. BMJ 343: d5326. [Prepared by Nicholas Taylor, CAP Editor.] QUESTION: Does manual lymph drainage prevent lymphoedema in patients who have had surgery for breast cancer?. DESIGN: Randomised, controlled trial with concealed allocation and blinded outcome assessment. SETTING: A multidisciplinary breast centre of a tertiary hospital in Belgium. PARTICIPANTS: Patients were eligible to be included if they received unilateral surgery with axillary node dissection for breast cancer, and agreed to participate. Randomisation of 160 participants allocated 79 to the intervention group and 81 to a control group. INTERVENTIONS: Both groups received guidelines about the prevention of lymphoedema in the form of a brochure, and exercise therapy involving supervised individualised 30 minute sessions - initially twice a week, reducing to once fortnightly as patients progressed. Participants in both groups were also asked to perform exercises at home twice/day. In addition, the intervention group received 40 sessions of manual lymph drainage over 20 weeks with each session lasting 30 minutes and performed by trained therapists. OUTCOME MEASURES: The primary outcomes were the cumulative incidence of and the time to develop arm lymphoedema (defined as a 200 ml increase) as measured with the water displacement method with measures taken at baseline and 1, 3, 6, and 12 months after surgery. Secondary outcome measures were lymphoedema measured with the arm circumference method, health-related quality of life using the SF-36 scale, and a patient reported questionnaire to score the presence of subjective arm lymphoedema. RESULTS: 154 participants (96%) completed the study at 12 months. At 12 months the incidence of lymphoedema in the intervention group (n=18, 24%) was similar to the incidence of lymphoedema in the control group (n = 15, 19%, OR 1.3, 95% CI 0.6 to 2.4); also there was no difference in incidence at 3 or 6 months. There was no difference between the groups in the time taken to develop lymphoedema, and no difference between the groups in any secondary outcome measure. CONCLUSION: The application of manual lymph drainage after axillary node dissection for breast cancer in addition to providing guidelines and exercise therapy did not prevent lymphoedema in the first year after surgery. PMID- 22093128 TI - General Health Questionnaire - 28 (GHQ-28). PMID- 22093129 TI - The Neer sign and Hawkins-Kennedy test for shoulder impingement. PMID- 22093133 TI - Recombinant DNA immunotherapy ameliorate established airway allergy in a IL-10 dependent pathway. AB - BACKGROUND: Previous studies have established that mycobacterial infections ameliorate allergic inflammation. However, a non-infectious approach that controls allergic responses might represent a safer and more promising strategy. The 60-65 kDa heat shock protein (Hsp) family is endowed with anti-inflammatory properties, but it is still unclear whether and how single mycobacterial Hsp control allergic disorders. OBJECTIVE: Therefore, in this study we determined whether the administration of Mycobacterial leprae Hsp65 expressed by recombinant a DNA plasmid could attenuate a previously established allergic response. METHODS: We used an experimental model of airway allergic inflammation to test the effects of immunotherapy with DNA encoding Hsp65. Allergic mice, previously sensitized and challenged with ovalbumin, were treated with tree intramuscular doses of recombinant DNA encoding Hsp65. After treatment, mice received a second allergen challenge and the allergic response was measured. RESULTS: We found that immunotherapy attenuated eosinophilia, pulmonary inflammation, Th2 cytokine and mucus production. Moreover, we showed that the inhibition of allergic response is dependent on IL-10 production. Both Hsp65 and allergen-specific IL-10-producing cells contributed to this effect. Cells transferred from DNA-immunized mice to allergic mice migrated to allergic sites and down-modulated the Th2 response. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings clearly show that immunotherapy with DNA encoding Hsp65 can attenuate an established Th2 allergic inflammation through an IL-10-dependent mechanism; moreover, the migration of allergen- and Hsp65-specific cells to the allergic sites exerts a fundamental role. This work represents a novel contribution to the understanding of immune regulation by Hsp65 in allergic diseases. PMID- 22093134 TI - Oral valganciclovir versus ganciclovir as delayed pre-emptive therapy for patients after allogeneic hematopoietic stem cell transplant: a pilot trial (04 0274) and review of the literature. AB - BACKGROUND: Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). This pilot prospective randomized clinical trial compares valganciclovir (VGV) to ganciclovir (GCV) as pre-emptive therapy for CMV viremia in the post-allogeneic HSCT population. METHODS: Patients undergoing allogeneic HSCT who were at risk for CMV viremia were monitored post HSCT by weekly quantitative whole blood polymerase chain reaction. Pre-emptive therapy was delayed until the viral load (VL) was >10,000 copies/mL once, or >5000 copies/mL twice. Patients were randomized to either GCV 5 mg/kg twice a day (b.i.d.) for 7 days followed by daily GCV 5 mg/kg for up to 21 days, or VGV 900 mg b.i.d. for 7 days followed by 900 mg daily for up to 21 days. The primary endpoint was clearance of viremia (VL <5000 copies/mL) within 28 days of initiation of therapy. RESULT: In total, 37 patients were enrolled; 19 patients received treatment with VGV and 18 patients received treatment with GCV. The VGV was not inferior in efficacy to GCV as pre emptive therapy, with rates of viral clearance at 28 days of 89.5% and 83%, respectively (P-value for non-inferiority = 0.030). Toxicities were similar between the 2 arms. No patients developed CMV disease. CONCLUSIONS: In this trial, the rates of clearance of viremia appear to be similar with VGV and GCV. PMID- 22093135 TI - Evaluation of process variations in noncompliance in the implementation of evidence-based sepsis care. AB - INTRODUCTION: Sepsis is recognized as an often-lethal disease. Recommended guidelines are complex and time sensitive. Response teams (RTs) have demonstrated success in implementation of quality initiatives. The purpose of this study was to evaluate variations in noncompliance with recommended sepsis guidelines overall and between a sepsis-focused RT and standard care. METHODS: This retrospective chart review categorized septic patients based on treatment by a sepsis response team (SRT) versus standard care (non-SRT). Guideline compliance was based upon the Surviving Sepsis evaluation and treatment guidelines. RESULTS: Patient records for 123 identified septic patients post first-year implementation were evaluated. Overall, compliance rates were low and there were variations in compliance between the treatment providers. The SRT was more compliant than the non-SRT. SRT noncompliance was more often due to failure to achieve therapeutic goals within the recommended time. Mortality benefit was not statistically significant between groups; however mortality was higher in the non-SRT group. CONCLUSION: Noncompliance is more complex than simple failure to initiate, especially in time-dependent therapies. The development and education of an RT demonstrates improvement in application of sepsis-focused therapies over standard care. PMID- 22093136 TI - [Pleural empyema caused by Streptococcus constellatus]. PMID- 22093137 TI - Effectiveness of laxatives in elderly--a cross sectional study in nursing homes. AB - BACKGROUND: Laxatives are efficient drugs, but the effectiveness has been questioned. In nursing homes, the prevalence of constipation is high and laxatives are commonly used drugs. The aims of the study were to assess the effectiveness of laxative therapy in an everyday setting in Norwegian nursing homes, study differences between treatment regimens and factors associated with normal bowel function. METHODS: A cross-sectional study. After giving informed consent, residents above 60 years of age using laxatives for functional constipation were included, and their characteristics, medical history, use of drugs and bowel functions were recorded. Normal bowel function was defined as bowel movements from 3 times/week to 3 times/day and stool consistency 3-5 on Bristol Stool Form Scale. RESULTS: Out of 647 residents in the nursing homes, 197 were included and 116 (59%) had normal bowel function. The treatment effect did not differ significantly between the laxatives, treatment regimens or expected efficacy of the regimens. The treatment was unsatisfactorily adapted to individual needs. In subjects with normal bowel function, 113 (97%) had persistent complaints; 68 (59.5%), 10 (8.0%), 34 (28.6%) and 26 (22.5%) reported straining, manual manoeuvre to facilitate bowel movements, feeling of incomplete bowel movements, and feeling of anorectal obstruction respectively. Good nutritional status, previous or present cancer disease and anxiety/depression were predictors of normal bowel function. CONCLUSIONS: Treatment of constipation in nursing homes was unsatisfactory. Nearly all patients with normal stool frequency and consistence had some persistent complaints. Improved nutrition and individualization of the treatment could improve the outcome. PMID- 22093138 TI - Mastication in humans: finding a rationale. PMID- 22093139 TI - External validity and psychiatric disorder exclusions in orofacial pain clinical trials. PMID- 22093140 TI - Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa. AB - BACKGROUND: Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV. RESULTS: We analyzed cross-sectional data collected from 404 HIV infected treatment-naive adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3) and CD4 (90 vs. 80 cells/mm3) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable. CONCLUSIONS: We demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease. PMID- 22093141 TI - Distal matrix glomus tumor presenting as longitudinal erythronychia: a pearl for surgical management. PMID- 22093142 TI - Intensive multifactorial treatment and cognitive functioning in screen-detected type 2 diabetes--the ADDITION-Netherlands study: a cluster-randomized trial. AB - AIM: To assess whether an intensive multifactorial treatment can reduce cognitive decrements and cognitive decline in screen-detected type 2 diabetes. METHODS: The multinational ADDITION-study, a cluster-randomized parallel group trial in patients with screen-detected type 2 diabetes, compared the effectiveness of intensive multifactorial treatment (IT; lifestyle advice and strict regulation of metabolic parameters) with routine care (RC) on cardiovascular outcome. In The Netherlands randomization was stratified according to practice organization. Allocation was concealed from patients. The present study assessed the effect of IT on cognition through two neuropsychological assessments (NPA) on two occasions. The assessments took place three and six years after the start of the intervention. Non-diabetic controls served as reference group. The first NPA was performed in 183 patients (IT: 97; RC: 86) and 69 controls. The second NPA was performed in 135 patients (IT: 71; RC: 64) and 55 controls. Primary outcome was a composite score, including the domains memory, information-processing speed and attention and executive function. Comparisons between the treatment groups were performed with multi-level analyses. RESULTS: The first NPA showed no differences between the treatment groups (mean difference composite z-score: 0.00; 95%-CI 0.16 to 0.16; IT vs RC). Over the next three years cognitive decline in the diabetic groups was within the range of the reference group and did not differ between the treatment arms (difference decline between diabetic groups -0.12; 0.24 to 0.01; IT vs RC). CONCLUSIONS: Six years of IT in screen-detected type 2 diabetes had no benefit on cognitive functioning over RC. PMID- 22093143 TI - Congenital vertebral duplication: a predisposing risk factor for dissection. AB - Spontaneous cervical-artery dissection (CAD) is a major cause of cerebral ischaemia in young adults. While their pathophysiology remains still poorly understood, CAD is considered today as a multifactorial disease determined by general and local predisposing factors; these predisposing factors being predominantly constitutional abnormalities of the arterial wall. Here, we report an MRI-confirmed dissection of a duplicated vertebral artery, in a patient with attacks of vertigo due to cerebellar infarction following a minor neck trauma. Knowing that another case of vertebrobasilar CAD on a duplicated vertebral artery has been reported, these rare anatomical variants probably predispose to vertebral CAD, via local histological defects or significant hemodynamics alterations, as reported for the classical local predisposing conditions for vertebral dissection, i.e.: fibromuscular dysplasias or carotid redundancies (including loops, kinks and coils). PMID- 22093144 TI - Value of prostate-specific antigen (PSA) mass ratio in the detection of prostate cancer in men with PSA levels of <=10 ng/mL. AB - A group of researchers introduced a parameter named PSA mass ratio, which is defined as total circulating PSA protein (PSA [ng/mL] x plasma volume [L]) per prostate volume, as a prostate cancer screening tool. They suggested that PSA mass ratio may be representative of a PSA value adjusted for potentially influencing factors, such as haemodilution and prostate volume. By adjusting for the combined effects of plasma volume and prostate volume, it can be hypothesized that PSA mass ratio would enhance the predictive value of the PSA test. Although PSA mass ratio appears to be an attractive alternative to serum PSA level, PSA mass ratio may not significantly enhance the currently available method to predict prostate cancer detection among men with PSA level of <=10 ng/mL who are undergoing prostate biopsy. OBJECTIVE: To investigate the value of prostate specific antigen (PSA) mass ratio, defined as total PSA in circulation per prostate volume (PV), in the prediction of prostate cancer detection among men with PSA levels of <=10 ng/mL who are undergoing prostate biopsy. PATIENTS AND METHODS: We reviewed records of 2431 men aged 56-80 years who presented with PSA levels of <=10 ng/mL and underwent multi (>=12)-core transrectal ultrasound guided prostate biopsy at our institution. Predictive accuracies of relevant variables and multivariate models in the prostate cancer detection via biopsy were assessed with receiver operating characteristics-derived area under the curve and compared. RESULTS: When compared one-on-one, PSA mass ratio had a significantly higher accuracy than PSA in the prediction of prostate cancer among our subjects (0.638 vs 0.565, P < 0.001). Meanwhile, when multivariable model for the prediction of prostate cancer detection via prostate biopsy was devised incorporating patient age, body mass index, digital rectal examination findings, PV, number of biopsy cores, and PSA level, the replacement of PSA level with PSA mass ratio (P = 0.102) or the addition of PSA mass ratio (P = 0.164) in the model was not associated with significantly increased accuracy of model for predicting prostate cancer detection via biopsy. CONCLUSION: Although PSA mass ratio appears to be an attractive alternative to PSA level, PSA mass ratio may not significantly enhance the currently available method to predict prostate cancer detection among men with PSA levels of <=10 ng/mL who are undergoing prostate biopsy. PMID- 22093145 TI - Targeting metabolism with arsenic trioxide and dichloroacetate in breast cancer cells. AB - BACKGROUND: Cancer cells have a different metabolic profile compared to normal cells. The Warburg effect (increased aerobic glycolysis) and glutaminolysis (increased mitochondrial activity from glutamine catabolism) are well known hallmarks of cancer and are accompanied by increased lactate production, hyperpolarized mitochondrial membrane and increased production of reactive oxygen species. METHODS: In this study we target the Warburg effect with dichloroacetate (DCA) and the increased mitochondrial activity of glutaminolysis with arsenic trioxide (ATO) in breast cancer cells, measuring cell proliferation, cell death and mitochondrial characteristics. RESULTS: The combination of DCA and ATO was more effective at inhibiting cell proliferation and inducing cell death than either drug alone. We examined the effect of these treatments on mitochondrial membrane potential, reactive oxygen species production and ATP levels and have identified new molecular mechanisms within the mitochondria for both ATO and DCA: ATO reduces mitochondrial function through the inhibition of cytochrome C oxidase (complex IV of the electron transport chain) while DCA up-regulates ATP synthase beta subunit expression. The potentiation of ATO cytotoxicity by DCA is correlated with strong suppression of the expression of c-Myc and HIF-1alpha, and decreased expression of the survival protein Bcl-2. CONCLUSION: This study is the first to demonstrate that targeting two key metabolic hallmarks of cancer is an effective anti-cancer strategy with therapeutic potential. PMID- 22093146 TI - Does a DNA-less cellular organism exist on Earth? AB - All the self-reproducing cellular organisms so far examined have DNA as the genome. However, a DNA-less organism carrying an RNA genome is suggested by the fact that many RNA viruses exist and the widespread view that an RNA world existed before the present DNA world. Such a possibility is most plausible in the microbial world where biological diversity is enormous and most organisms have not been identified. We have developed experimental methodology to search DNA less microorganisms, which is based on cultivation with drugs that inhibit replication or expression of DNA, detection of DNA in colonies with a fluorescent dye and double staining for DNA and RNA at a cellular level. These methods have been applied for about 100 microbial samples from various waters including hot springs, soils including deep sea sediments, and organisms. We found many colonies and cells which apparently looked DNA-less and examined them further. So far, all such colonies that reformed colonies on isolation were identified to be DNA-positive. However, considering the difficulty in cultivation, we think it possible for DNA-less microorganisms to live around us. We believe that our ideas and results will be of interest and useful to discover one in the future. PMID- 22093147 TI - Value of tracheal bifurcation angle measurement as a radiographic sign of left atrial enlargement in dogs. AB - An increased tracheal bifurcation angle on the dorsoventral projection is described as a sign of left atrium enlargement in dogs, with a normal range of 60 90 degrees reported. However in people, this angle is a poor indicator of left atrial size. Our purpose was to evaluate the value of the tracheal bifurcation angle for differentiating normal from enlarged left atrium in dogs. Dorsoventral radiographs and echocardiograms of 33 healthy and 73 dogs with confirmed degenerative myxomatous mitral valve disease were evaluated. Left atrial size was classified according to the echocardiographic left atrium to aorta ratio, as normal, mildly, moderately, or severely enlarged. Independent samples t-tests were used to compare the bifurcation angle between groups. A significant difference was observed between the angle of dogs with normal left atrium (68.1 +/- 8.5 degrees, range: 51.3-92.4 degrees) and dogs with enlarged left atrium (75.8 +/- 8.2 degrees, range: 57.3-91.7 degrees). A significant difference was also noted between the angle of normal dogs and those with moderate (75.5 +/- 6.8 degrees, range: 62.8-88.7 degrees) and severe (80.4 +/- 7.7 degrees, range: 64.7 91.7 degrees) left atrial enlargement, as well as between dogs with mild (70.7 +/ 7.2 degrees, range: 57.3-89.9 degrees) and severe enlargement. Using two discriminators, 85.1 degrees and 76.6 degrees, the bifurcation angle had a specificity of 92.6% and 88.9%, respectively, for identifying left atrial enlargement, and a sensitivity of 15.4% and 40.4%. Although significant differences were observed between dogs with normal and increased left atrial size, the large degree of overlap in the range of bifurcation angles and its poor sensitivity make the measurement of this angle of little value for diagnosing left atrial enlargement. PMID- 22093148 TI - Two decades of describing the unseen majority of aquatic microbial diversity. AB - Aquatic environments harbour large and diverse microbial populations that ensure their functioning and sustainability. In the current context of global change, characterizing microbial diversity has become crucial, and new tools have been developed to overcome the methodological challenges posed by working with microbes in nature. The advent of Sanger sequencing and now next-generation sequencing technologies has enabled the resolution of microbial communities to an unprecedented degree of precision. However, to correctly interpret microbial diversity and its patterns this revolution must also consider conceptual and methodological matters. This review presents advances, gaps and caveats of these recent approaches when considering microorganisms in aquatic ecosystems. We also discuss potentials and limitations of the available methodologies, from water sampling to sequence analysis, and suggest alternative ways to incorporate results in a conceptual and methodological framework. Together, these methods will allow us to gain an unprecedented understanding of microbial diversity in aquatic ecosystems. PMID- 22093149 TI - Successful treatment of Trichosporon fungemia in a patient with refractory acute myeloid leukemia using voriconazole combined with liposomal amphotericin B. AB - Trichosporon fungemia is a rare and fatal fungal infection that occurs in patients with prolonged neutropenia associated with hematologic malignancies. A 21-year-old male developed Trichosporon fungemia during remission induction therapy for acute myeloid leukemia (AML). Although two courses of induction therapy failed to induce a remission of AML, combination therapy with voriconazole and liposomal amphotericin B (L-AmB) followed by monocyte colony stimulating factor ameliorated the Trichosporon fungemia and enabled the patient to receive reduced-intensity bone marrow transplantation (BMT) from his human leukocyte antigen-A one-locus mismatched mother. The patient achieved a durable remission after BMT without exacerbation of Trichosporon fungemia. The combination therapy with voriconazole and L-AmB may therefore be useful in controlling Trichosporon fungemia associated with prolonged neutropenia after remission induction therapy for AML. PMID- 22093150 TI - The psychological impact of diagnostic food challenges to confirm the resolution of peanut or tree nut allergy. AB - BACKGROUND: Twenty percent of children outgrow peanut allergy and 10% outgrow tree nut allergy. Resolution can be confirmed by a food challenge. Little is known about the psychosocial impact of the challenge. We aimed to investigate effects of a food challenge on anxiety, stress and quality of life (QoL) in children and their mothers on the day of a food challenge to peanuts or nuts, and in the months following the challenge. METHODS: One hundred and three families participated. Forty children undergoing food challenges to access resolution of allergy, and their mothers, completed validated questionnaires to measure generic and food specific quality of life, stress and anxiety prior to challenge, on the day of investigation and 3-6 months later. Sixty-three children with no clinical indication to challenge (i.e. in the opinion of the allergist had persistent allergy) acted as comparison group completing questionnaires 3-6 months apart. RESULTS: Mothers reported raised anxiety on the day of challenge (P = 0.007), but children were less anxious. The children (P = 0.01) and mothers (P = 0.01) had improved food-related, but not general, QoL 3-6 months following challenge. Children reported lower anxiety levels following the challenge (P = 0.02), but anxiety remained unchanged in mothers. The improvements in maternal and children's QoL and anxiety levels were irrespective of the challenge outcome and despite co-existing food allergies in 50% of children. CONCLUSIONS: Mothers experienced increased anxiety on the day of food challenge, unlike the children, perhaps reflecting the differences in their perceived risks. Food challenges are associated with improved food-related QoL in the following months even in those with a positive challenge. PMID- 22093151 TI - Testing children of mothers with HIV infection: experience in three south-west London HIV clinics. AB - OBJECTIVE: There are several reported cases of vertically infected children presenting with advanced HIV infection in the UK. The children of women with HIV infection are at increased risk of being infected. There are few data available on the number of such children that are yet to be tested for HIV. This study looked at the HIV testing status of children whose mothers attend HIV services at three south-west London clinics. METHODS: Case notes of women attending the clinics from 1 January to 30 June 2009 were reviewed. When data were incomplete, women were prospectively interviewed. RESULTS: Case notes of 605 women were reviewed; 478 women had 1107 children. The majority of women (386; 81%) were of Black African ethnicity. Sixty-one per cent (675 of 1107) of the children were known to have been tested for HIV. The children resident abroad were more likely to be untested compared with those resident in the UK; 186 of 255 (73%) vs. 246 of 852 (29%). A quarter (106 of 432) of the untested children were <= 18 years old; 49 (46%) of these were resident in the UK. The most common reason given by the mothers for not testing was a perceived 'unlikely risk'. CONCLUSIONS: A significant number of children at risk of vertically transmitted HIV infection, including 49 children <= 18 years and resident in the UK, were identified through this study. The mothers are being encouraged to have these children tested and a multidisciplinary team involving adult and paediatric HIV healthcare professionals has been set up to negotiate and facilitate testing. PMID- 22093152 TI - Behavioral autonomy age expectations among Mexican-origin mother-daughter dyads: an examination of within-group variability. AB - This study examined differences in behavioral autonomy age expectations between Mexican-origin mothers and their adolescent daughters (N = 319 dyads); variability in behavioral autonomy age expectations as a function of nativity and maternal educational attainment also was examined. Findings indicated significant differences between mothers and daughters, such that mothers reported later expectations for the timing of behavioral autonomy than did daughters. Follow-up analyses indicated that findings appeared to be driven by maternal nativity, with dyads comprised of Mexico-born mothers reporting the latest age expectations for behavioral autonomy when compared with dyads comprised of U.S. born mothers. Findings underscore the need to examine normative development among Latino adolescents and their families with a specific focus on how sociocultural characteristics can contribute to within-family differences. PMID- 22093153 TI - Is liver-targeted FOXp3 staining beneficial after living-donor liver transplantation? AB - As treatments for acute cellular rejection (ACR) and recurrent hepatitis caused by hepatitis C virus (HCV) are dramatically different, making a precise diagnosis is considered to be essential in patients after liver transplantation. Therefore, we investigated whether immunohistochemical detection of FOXp3, a marker for regulatory T cells (CD4+ CD25+), could be used to differentiate between recurrent hepatitis C and ACR. From a group of 103 cases of living-donor liver transplantation (LDLT), 48 samples were taken via liver biopsy from 20 patients with HCV infection. An initial diagnosis was made based on hematoxylin and eosin staining, which was scored with the hepatitis activity index (HAI) grading, whereas ARC was scored with the rejection activity index (RAI). The FOXp3 immunohistochemical staining on serial specimens was retrospectively analyzed, scoring from 0 to III. The time after LDLT was a median of 270 (range: 14-2000) days, whereas the median number of biopsies per patient was 3 (range: 1-8). The HAI was significantly different between 0 vs. I, and II vs. III, in terms of the FOXp3 score. On the other hand, a significant difference in the RAI was only found between 0 vs. I. In conclusion, FOXp3 may represent a surrogate marker for recurrent HCV infection after LDLT. PMID- 22093154 TI - Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice. AB - Enriched environments (EEs) during development have been shown to influence adult behaviour. Environmental conditions during childhood may contribute to the onset and/or pathology of schizophrenia; however, it remains unclear whether EE might prevent the development of schizophrenia. Herein, we investigated the effects of EE during adolescence on phencyclidine (PCP)-induced abnormal behaviour, a proposed schizophrenic endophenotype. Male ICR mice (3 wk old) were exposed to an EE for 4 wk and then treated with PCP for 2 wk. The EE potentiated the acute PCP treatment-induced hyperlocomotion in the locomotor test and prevented chronic PCP treatment-induced impairments of social behaviour and recognition memory in the social interaction and novel object recognition tests. It also prevented the PCP induced decrease of acetylated Lys9 in histone H3-positive cells and increase of the histone deacetylase (HDAC)5 level in the prefrontal cortex. To investigate whether the histone modification during adolescence might be critical for the effect of EE, 3-wk-old mice were first treated with sodium butyrate (SB; an HDAC inhibitor) for 4 wk and then treated with PCP for 2 wk. Chronic SB treatment during adolescence mimicked the effects of EE, including potentiation of hyperlocomotion induced by acute PCP treatment and prevention of social and cognitive impairments, decrease of acetylated Lys9 in histone H3-positive cells and increase of the HDAC5 level in the prefrontal cortex associated with chronic PCP treatment. Our results suggest that EEs prevent PCP-induced abnormal behaviour associated with histone deacetylation. EEs during childhood might prove to be a novel strategy for prophylaxis against schizophrenia. PMID- 22093156 TI - Laser-assisted lipolysis: a review. AB - BACKGROUND: In the United States, liposuction is the most commonly performed cosmetic surgical procedure. Laser lipolysis is the latest adjunct to liposuction. This technique employs laser energy to induce lipolysis and hemostasis and stimulate neocollagenesis. Multiple laser systems have been studied. METHODS: PubMed literature search with the key words laser lipolysis and laser assisted liposuction. Original articles that studied the internal application of laser energy to adipose tissue were reviewed and included. RESULTS: Nineteen manuscripts were reviewed. One double-blind randomized controlled trial compared laser liposuction with tumescent liposuction. Several authors claimed that laser lipolysis offers fewer side effects than "traditional" liposuction performed under general anesthesia. A true objective comparison with tumescent liposuction is missing in the literature. LIMITATIONS: Comparison studies between laser-assisted lipolysis and conventional liposuction are limited, as are comparisons between the different laser systems and wavelengths. Standardization of laser energy settings is lacking. CONCLUSION: Laser-assisted lipolysis is a safe and efficacious procedure that may possess advantages over conventional liposuction. Lipolysis occurs in a dose-response relationship. No advantage over tumescent liposuction has been demonstrated. A specific laser wavelength may prove superior for each clinical application, but more studies are needed. PMID- 22093155 TI - Factors associated with smoking abstinence among smokers and recent-quitters with lung and head and neck cancer. AB - INTRODUCTION: Smoking cessation among cancer patients is critical for improving outcomes. Understanding factors associated with smoking abstinence after the diagnosis of cancer can provide direction to develop and test interventions to enhance cessation rates. The purpose of this study was to identify determinants of smoking outcomes among cancer patients. METHODS: Standardized questionnaires were used to collect data from 163 smokers or recent-quitters (quit<=6 months) at study entry of which 132 and 121 had data collected at 3 and 6 months. Biochemical verification was conducted with urinary cotinine and carbon monoxide. Descriptive statistics, Cronbach alpha coefficients, Pearson correlations, Fisher's exact test, and multivariable logistic regression were used for analyses. RESULTS: Seven-day-point-prevalence-abstinence (PPA) rates were 90/132 (68%) at 3 months; 46/71 (65%) among lung and 44/61 (72%) among head and neck cancer patients, whereas 7-day-PPA rates were 74/121 (61%) at 6 months; 31/58 (53%) among lung and 43/63 (68%) among head and neck cancer patients. Continuous abstinence rates were 63/89 (71%) at 3 months; 32/45 (71%) among lung and 31/44 (70%) among head and neck cancer patients, whereas continuous abstinence rates were 46/89 (52%) at 6 months; 18/45 (40%) among lung and 28/44 (64%) among head and neck cancer patients. Lower cancer-related, psychological and nicotine withdrawal symptoms were associated with increased 7-D-PPA abstinence rates at 3 and 6 months in univariate models. In multivariable models, however, decreased craving was significantly related with 7-day-PPA at 3 months and decreased craving and increased self-efficacy were associated with 7-D-PPA at 6 months. Decreased craving was the only factor associated with continuous abstinence at 6 months. CONCLUSIONS: Smoking outcomes among lung and head and neck cancer patients appear to have remained the same over the last two decades despite the availability of an increased number of pharmacotherapy options to treat tobacco dependence. Decreased craving and increased self-efficacy were the most consistent factors associated with improved smoking outcomes but symptom control may also play a role in optimal management. Use of combined, and/or higher doses of pharmacotherapy along with behavioral interventions that increase self efficacy and manage symptoms may promote enhanced cessation rates. PMID- 22093157 TI - Do lean practices lead to more time at the bedside? AB - The aim of this review is to evaluate the application of value-added processes in healthcare, with an emphasis on their effects on bedside nursing. Literature relevant to Lean methodology and inpatient care was reviewed, excluding all research related to other service lines (i.e., surgical services, emergency services, laboratory, radiology, etc.). Increased value is also an important tenet of transforming care at the bedside (TCAB), an initiative launched by the Institute for Healthcare Improvement (IHI) and the Robert Wood Johnson Foundation (RWJF). Therefore, articles concerning TCAB were also included in this review. A systematic study of the literature revealed varied applications of Lean principles in practice, ranging from the implementation of a single tool, to full organizational restructuring. All articles reviewed reported positive results, although the majority lacked strong supporting evidence for claims of improvement. Even though there is some indication that the application of Lean principles to nursing processes is successful in improving specific outcomes, the authors cannot conclude that the implementation of Lean methodology or TCAB greatly influences direct patient care, or increases time spent at the bedside. PMID- 22093158 TI - Clinical trial for safety evaluation of hyaluronidase as diffusion enhancing adjuvant for infiltration analgesia of skin with lidocaine. AB - BACKGROUND: Infiltration anesthesia of the skin is an analgesic procedure often practiced before minor surgical interventions or punctures. The addition of hyaluronidase is a possible option to improve the effectiveness of the local anesthetic with respect to expansion of effect. OBJECTIVE: To validate the safety of intracutaneous application of hyaluronidase as a lidocaine adjuvant. MATERIALS AND METHODS: The influence of adjuvant hyaluronidase on wound healing was investigated using the suction blister method in a prospective, single-center, placebo-controlled, double-blind, intraindividual comparison study with 20 participants. The target parameters were defined as the time of normalization of transepidermal water loss, hemovascular perfusion, and complete macroscopic epithelization of the wound. RESULTS: No evidence was found that adjuvant application of hyaluronidase retards wound healing. CONCLUSION: The addition of hyaluronidase to lidocaine in intracutaneous infiltration analgesia does not lead to retardation of wound healing, and no additional relevant risks were observed. PMID- 22093159 TI - Loss of sensory and noradrenergic innervation in benign colorectal adenomatous polyps--a putative role of semaphorins 3F and 3A. AB - BACKGROUND: Nerve fibers can exert trophic/anti-trophic effects on epithelial cells. Substance P (SP) is a pro-proliferative neuropeptide, whereas sympathetic noradrenaline is anti-proliferative at high concentrations. METHODS: Density of noradrenergic and sensory nerve fibers and presence of nerve repellent factors specific for noradrenergic (semaphorin 3F) and sensory nerve fibers (semaphorin 3A) were investigated in colorectal adenomas. KEY RESULTS: The pedunculus was innervated by noradrenergic fibers, whereas the mucosa was sparsely innervated. The control submucosa compared with control mucosa demonstrated increased density of noradrenergic fibers. Control tissue was much better innervated than the polyp. This was accompanied by strong expression of semaphorin 3F in epithelial cells. Density of sensory SP+ nerve fibers was higher in control colon mucosa compared with polyp mucosa, and SP+ cell clusters and semaphorin 3A-positive cells appeared in the intercrypt space in polyps, but not in control tissue. CONCLUSIONS & INFERENCES: This study demonstrated a marked loss of noradrenergic and sensory nerve fibers in polyp mucosa, which was associated with a strong increase of semaphorin 3F and 3A. Up-regulation of the sympathetic repellent semaphorin 3F in the polyps possibly triggers sympathetic repulsion and polyp growth due to the loss of anti-proliferative noradrenaline and presence of SP from local SP+ cells. PMID- 22093160 TI - The burden of varicella from a parent's perspective and its societal impact in The Netherlands: an Internet survey. AB - BACKGROUND: Varicella is a common childhood disease. Only 5% of first varicella zoster-virus infections occur asymptomatically. Most data on the burden of varicella stem from health service databases. This study aims to provide insight in the burden of varicella from a parent's perspective including cases outside the healthcare system. METHODS: An internet questionnaire was developed for parents in the Netherlands to report health care resource use and productivity losses during the varicella episode in their child younger than 6 years. 11,367 invitations were sent out to members with children of an internet panel of a market research agency. 4,168 (37%) parents started the questionnaire (response rate), of which 360 (9%) stopped before completion and 1,838 (44%) were out of the target group. In total 1,970 parents completed the questionnaire. The questionnaire provided a symptom list ranging from common symptoms, such as skin vesicles, itching to fits or convulsions. A posteriori, in the analyses, the symptoms 'skin infections', 'fits/convulsions', 'unconsciousness', and 'balance and movement disorders' were labelled as complications. There was no restriction to time since the varicella episode for inclusion in the analyses. RESULTS: The 1,970 respondents had in total 2,899 children aged younger than six years, of which 2,564 (88%) children had had varicella. In 62% of the episodes the parent did not seek medical help. In 18% of all episodes symptoms labelled as complications were reported; in 11% of all episodes parents visited a medical doctor (MD) for a complication. Reporting of complications did not differ (X2 ; p = 0.964) between children with a recent (<= 12 months ago) or a more distant (> 12 months) history of varicella. Prescription drugs were used in 12% of the children with varicella; OTC drugs in 72%. Parents reported work loss in 17% of the varicella-episodes (23% when MD visit; 14% when no MD-visit) for on average 14 hours, which equals to 2.5 hours of work loss for any given varicella-episode. CONCLUSIONS: This study shows the full spectrum of varicella-episodes and associated healthcare use, including the large proportion of cases not seeking medical care and the societal impact associated with those cases. PMID- 22093161 TI - Dermoscopic features of basal cell carcinomas: differences in appearance under non-polarized and polarized light. AB - BACKGROUND: Basal cell carcinomas (BCCs) can be diagnosed using different dermoscopic modalities. OBJECTIVE: To evaluate dermoscopic features of BCCs using nonpolarized and polarized dermoscopy to highlight similarities and differences between dermoscopic modalities. MATERIALS AND METHODS: Retrospective study of 149 BCCs under nonpolarized dermoscopy (NPD), polarized contact dermoscopy (PCD), and polarized noncontact dermoscopy (PNCD). Images were evaluated for a range of dermoscopic colors, structures, and vessels. Features were compared according to histopathologic subtype. RESULTS: The most common dermoscopic structures in BCCs across all modalities included globules (50.3-51.0%), dots (49.7-50.3%), white structureless areas (63.1-74.5%), structureless gray-brown areas (24.2-24.8%), and ulcerations (28.2%). The most frequently observed vasculature included arborizing vessels (18.8-38.3%), short fine telangiectasias (SFTs) (73.8-82.6%), and vascular blush (41.6-83.2%). Structures with higher levels of agreement across modalities included pigmented structures and ulcerations. Lower levels of agreement existed between contact and noncontact modalities for certain vascular features. White shiny structures, which include shiny white lines (chrysalis and crystalline structures) (0-69.1%), shiny white areas (0-25.5%), and rosettes (0 11.4%), exhibited no agreement between NPD and polarized modalities. CONCLUSIONS: This study highlights differences in dermoscopic features of BCCs under three dermoscopic modalities. Shiny white lines (chrysalis and crystalline structures) and shiny white areas may be used as additional criteria to diagnose BCCs. PMID- 22093162 TI - Prostate cancers detected by saturation repeat biopsy impairs the Partin tables' accuracy to predict final pathological stage. AB - OBJECTIVE: * To analyse the overall accuracy of Partin tables, with special emphasis to potential limitations resulting from differences between prostate cancers detected by different biopsy schedules. PATIENTS AND METHODS: * Clinical characteristics from 599 patients treated with radical prostatectomy defined the 2007 Partin probabilities of organ confinement (OC), seminal vesicle invasion (SVI) and extracapsular extension (ECE). Prostate cancers were detected by initial biopsy (IBx) with <=12 cores in 405 patients (67.6%), by conventional repeat biopsy (CRBx) with <=12 cores in 99 (16.5%) and by saturation repeat biopsy (SRBx) with >=20 cores in 95 patients (15.9%). * The area under the curve (AUC) estimated by the receiver operating characteristic curve, assessed the predictive accuracy of the 2007 Partin tables. RESULTS: * The Partin tables AUC of the IBx, CRBx and the SRBx groups were 0.730 vs 0.701 vs 0.585 for OC, 0.631 vs 0.689 vs 0.547 for ECE, and 0.775 vs 0.755 vs 0.641 for SVI, respectively. CONCLUSIONS: * The overall accuracy of the 2007 Partin tables was clearly inferior in patients with prostate cancers detected by SRBx. * Prostate cancers detected by SRBx undermine the Partin tables' overall accuracy, and this group of patients may be miscounselled by vague predictions. PMID- 22093163 TI - Contrast stress echocardiography in hypertensive heart disease. AB - Hypertension is associated with atherosclerosis and cardiac and vascular structural and functional changes. Myocardial ischemia may arise in hypertension independent of coronary artery disease through an interaction between several pathophysiological mechanisms, including left ventricular hypertrophy, increased arterial stiffness and reduced coronary flow reserve associated with microvascular disease and endothelial dysfunction. The present case report demonstrates how contrast stress echocardiography can be used to diagnose myocardial ischemia in a hypertensive patient with angina pectoris but without significant obstructive coronary artery disease. The myocardial ischemia was due to severe resistant hypertension complicated with concentric left ventricular hypertrophy and increased arterial stiffness. PMID- 22093164 TI - Performance of the digene LQ, RH and PS HPVs genotyping systems on clinical samples and comparison with HC2 and PCR-based Linear Array. AB - BACKGROUND: Certain Human Papillomaviruses (HPVs) are the infectious agents involved in cervical cancer development. Detection of HPVs DNA is part of the cervical cancer screening protocols and HPVs genotyping has been proposed for its inclusion in these preventive programs. The aim of this study was to evaluate three novel genotyping tests, namely Qiagen LQ, RH and PS, in clinical samples with and without abnormalities. For this, 305 cervical samples were processed and the results of the evaluated techniques were compared with those obtained in the HPVs diagnostic process in our lab, by using HC2 and Linear Array (LA) technologies. RESULTS: The concordances and kappa statistics (k) for each technique compared with HC2 were 98.69% (k = 0.94) for LQ, 98.03% (k = 0.91) for RH and 91.80% (k = 0.82) for PS. There was a very good agreement in HPVs type specific concordance for the most prevalent types HPV16 (kappa range = 0.83 0.90), HPV18 (k.r.= 0.74-0.80) and HPV45 (k.r.= 0.82-0.90). CONCLUSIONS: The three tests showed an overall good concordance for HPVs detection when compared with HR-HC2 system. LQ and RH rendered lower detection rate for multiple infections than LA genotyping. However, our understanding of the clinical significance of multiple HPVs infections is still incomplete and therefore the relevance of the lower ability to detect multiple infections needs to be evaluated. PMID- 22093165 TI - Microbial ureteral stent colonization in renal transplant recipients: frequency and influence on the short-time functional outcome. AB - Ureteral stent insertion at the time of renal transplantation significantly decreases complications of urine leakage and obstruction, but bears an intrinsic risk of microbial colonization. Associated urinary tract infection (UTI) may pose a significant risk for graft infection and subsequent graft failure, in particular, during high-level immunosuppression in the early phase after transplantation. The aims of this prospective study were (i) to assess the frequency of microbial ureteral stent colonization (MUSC) in renal transplant recipients by sonication, (ii) to compare the diagnostic value of sonication with that of conventional urine culture (CUC), (iii) to determine biofilm forming organisms, and (iv) to investigate the influence of MUSC on the short-time functional outcome. A total of 80 ureteral stents from 78 renal transplant recipients (deceased donors n = 50, living donors n = 28) were prospectively included in the study. CUC was obtained prior to renal transplantation and at ureteral stent removal. In addition, a new stent sonication technique was performed to dislodge adherent microorganisms. CUCs were positive in 4% of patients. Sonicate-fluid culture significantly increased the yield of microbial growth to 27% (P < 0.001). Most commonly isolated microorganisms by sonication were Enterococcus species (31%), coagulase-negative staphylococci (19%), and Lactobacillus species (19%), microorganisms not commonly observed in UTIs after renal transplantation. The median glomerular filtraton rate (GFR) of the study population increases from 39 mL/min immediately after transplantation (time point A) to 50 mL/min 6 month post transplantation (time point B). In patients without MUSC, the GFR improves from 39 mL/min (A) to 48 mL/min (B) and in patients with MUSC from 39 mL/min (A) to 50 mL/min (B), respectively. In summary, MUSC in renal transplant recipients is common and remains frequently undetected by routine CUC, but colonization had no measurable effect on renal function. PMID- 22093166 TI - Biochemical and genetical analyses of the three mcm genes from the hyperthermophilic archaeon, Thermococcus kodakarensis. AB - In eukaryotes, the replicative DNA helicase 'core' is the minichromosome maintenance (Mcm) complex (MCM), forming a heterohexameric complex consisting of six subunits (Mcm2-7). Recent studies showed that the CMG (Cdc45-MCM-GINS) complex is the actual helicase body in the replication fork progression complex. In Archaea, Thermococcus kodakarensis harbors three genes encoding the Mcm homologs on its genome, contrary to most archaea, which have only one homolog. It is thus, of high interest, whether and how these three Mcms share their functions in DNA metabolism in this hyperthermophile. Here, we report the biochemical properties of two of these proteins, TkoMcm1 and TkoMcm3. In addition, their physical and functional interactions with GINS, possibly an essential factor for the initiation and elongation process of DNA replication, are presented through in vitro ATPase and helicase assays, and an in vivo immunoprecipitation assay. Gene disruption and product quantification analyses suggested that TkoMcm3 is essential for cell growth and plays a key role as the main DNA helicase in DNA replication, whereas TkoMcm1 also shares some function in the cells. PMID- 22093167 TI - Fatty acid binding protein 4 is expressed in distinct endothelial and non endothelial cell populations in glioblastoma. AB - AIMS: Glioblastoma (GBM) is the most common and aggressive primary brain tumour in adults. Angiogenesis and vasculogenesis play key roles in progression of GBMs. Fatty acid binding protein 4 (FABP4) is an intracellular chaperone for free fatty acids. FABP4 is detected in microvascular endothelial cells (ECs) in several normal tissues and promotes proliferation of ECs. The goal of this study was to characterize the tissue distribution pattern of FABP4 in GBMs. METHODS: Immunohistochemistry for FABP4 was performed on paraffin-embedded tumour sections and the intensity and distribution of FABP4 immunoreactivity were analysed. Double immunofluorescence was employed for detailed characterization of FABP4 positive cells. RESULTS: FABP4 immunoreactivity was absent in normal brain tissue sections. FABP4-positive cells were detected in 33%, 43%, 64% and 89% of Grade I, Grade II, Grade III and Grade IV glial tumours, respectively. Thus, the percentage of FABP4-positive cells in GBMs was significantly higher than lower grade gliomas. In general, FABP4-expressing cells were distributed in a non homogenous pattern, as 'hot spots' in glial tumours. FABP4 expression was detected in a subset of vascular ECs as well as some non-ECs. CONCLUSION: FABP4 is expressed in a significantly higher percentage of GBMs in comparison to both normal brain tissues and lower-grade glial tumours. FABP4 is expressed in some tumour ECs as well as non-ECs in glial tumours. As FABP4 promotes proliferation of ECs, detection of FABP4 in GBM-ECs, but not normal brain ECs suggests that FABP4 may play a role in the robust angiogenesis associated with GBMs. PMID- 22093168 TI - MRI features of CNS lymphoma in dogs and cats. AB - The magnetic resonance (MR) imaging features of central nervous system lymphoma in eight dogs and four cats are described. Intracranial lesions affected the rostrotentorial structures in six dogs and caudotentorial structures in two cats. Lesions affected the spinal cord in two dogs and in two cats. One dog and one cat with intracranial lymphoma had signs of local extracranial extension and lymphadenopathy. Lesions were considered extraparenchymal in four dogs and three cats, intraparenchymal in two dogs and one cat, and appeared to have both intra- and extraparenchymal components in two dogs. All lesions were hyperintense in T2 weighted images when compared to white matter, most were hypointense in T1 weighted images (7/12), and most were hyperintense in fluid-attenuated inversion recovery (FLAIR) images (5/9). When compared to grey matter, these lesions appear either isointense (5/12) or hyperintense (7/12) on T2-weighted images, half of them were hypointense in T1-weighted images (6/12), and most were isointense in FLAIR images (7/9). Lesion margins were usually indistinct in T2-weighted images (10/12) and had perilesional hyperintensity in FLAIR images (7/9). The majority of lesions (10/12) had abnormal meninges around the lesion and half (6/12) had generalized contrast enhancement. Mass effect was evident in all lesions. Although not specific, when combined with the history and neurologic signs, MR features aid presumptive diagnosis that should be confirmed by cytology or histopathology. PMID- 22093169 TI - Haloperidol conditioned catalepsy in rats: a possible role for D1-like receptors. AB - Decreases in brain dopamine (DA) lead to catalepsy, quantified by the time a rat remains with its forepaws resting on a suspended horizontal bar. Low doses of the DA D2 receptor-preferring antagonist haloperidol repeatedly injected in a particular environment lead to gradual day-to-day increases in catalepsy (catalepsy sensitization) and subsequent testing following an injection of saline reveal conditioned catalepsy. We tested the hypothesis that D1-like and D2 receptors play different roles in catalepsy sensitization and in acquisition and expression of conditioned catalepsy. Rats were repeatedly treated with the DA D1 like receptor antagonist SCH 23990 (0.05, 0.1 and 0.25 mg/kg i.p.), the D2 receptor-preferring antagonist haloperidol (0.1, 0.25 and 0.5 mg/kg i.p.) or a combination of the two drugs and tested for catalepsy each day in the same environment. Following 10 drug treatment days, rats were injected with saline and tested for conditioned catalepsy in the previously drug-paired environment. Haloperidol did not elicit cataleptic responses in the initial session; however, rats developed sensitization with repeated testing. Significant catalepsy sensitization was not observed in rats repeatedly tested with SCH 23390. When rats were injected and tested with saline following haloperidol sensitization they exhibited conditioned catalepsy in the test environment; conditioned catalepsy was not seen following SCH 23390. Rats treated with 0.05 mg/kg SCH 23390+0.25 mg/kg haloperidol showed catalepsy sensitization but failed to show conditioned catalepsy. Conversely, SCH 23390 (0.05 mg/kg) given on the test day after sensitization to haloperidol (0.25 mg/kg) failed to block conditioned catalepsy. Repeated antagonism of D2 receptors leads to catalepsy sensitization with repeated testing in a specific environment. Conditioned catalepsy requires intact D1-like receptor function during sensitization sessions but not during test sessions. In conclusion, repeated antagonism of D2, but not D1-like receptors leads to catalepsy sensitization with repeated testing in a specific environment. Conditioned catalepsy requires functional D1-like receptors during sensitization sessions but not during test sessions. PMID- 22093170 TI - Interview with a quality leader: Dr. Verna Gibbs on surgical safety. Interview by Susan V. White. AB - Dr. Verna Gibbs describes the "NoThing Left Behind" Program designed to eliminate retained devices from surgical procedures. She explains the genesis of the program along with adjuncts to counting including computer-assisted sponge count, radiofrequency detection system, radiofrequency identification system, and the Sponge ACCOUNTing system. She provides comments on the use of these adjuncts with responses on their effectiveness on improving safety. PMID- 22093172 TI - Pneumocystis jirovecii pneumonia in kidney transplantation. AB - Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised renal transplant recipients. In recent years, PCP outbreaks in renal transplant centers have been reported in many countries. Person-to-person transmission between PCP patients and other recipients lacking prophylaxis is one of the possible sources of infection. To prevent infection, effective prophylaxis in susceptible patients is recommended. Trimethoprim sulfamethoxazole (TMP-SMX) is the most effective drug for PCP prophylaxis, but its recommended duration of use after transplantation varies among the different guidelines. The European Renal Association recommends a prophylaxis period of 4 months after transplantation, the American Society of Transplantation (AST) 6-12 months, and the Kidney Disease Improving Global Outcomes guidelines 3-6 months. Lifelong prophylaxis with TMP-SMX is not recommended in renal transplant recipients; however, in many cases, PCP has occurred after the recommended prophylaxis periods after transplantation. In this minireview, we discuss the risk factors including environmental-nosocomial exposure; state-of-the-art diagnosis, treatment, prophylaxis and isolation; and references to the AST 2009 guidelines with the aim of integrating our experience with PCP outbreaks into recent reports, and we discuss how renal transplant recipients can be protected from PCP. PMID- 22093171 TI - Late presentation for HIV diagnosis and care in Germany. AB - OBJECTIVES: Antiretroviral therapy reduces mortality and morbidity in HIV infected individuals most markedly when initiated early, before advanced immunodeficiency has developed. Late presentation for diagnosis and care remains a significant challenge. To guide public health interventions effectively it is crucial to describe the factors associated with late presentation. METHODS: Case surveillance data for all individuals newly diagnosed with HIV infection in Germany in the years 2001-2010 and data for the years 1999-2010 from the German Clinical Surveillance of HIV Disease (ClinSurv) cohort study, a large multicentre observational study, were analysed. Factors associated with late presentation (CD4 count < 350 cells/MUL or clinical AIDS) were assessed using descriptive statistics and multivariable logistic regression methods. RESULTS: Among 22 925 eligible patients in the national surveillance database, 49.5% were late presenters for HIV diagnosis. Among 6897 treatment-naive patients in the ClinSurv cohort, 58.1% were late presenters for care. Late presenters for care were older (median 42 vs. 39 years for early presenters), more often heterosexuals from low prevalence countries (18.1% vs. 15.5%, respectively) and more often migrants (18.2% vs. 9.7%, respectively; all P < 0.005). The probability of late presentation was >65% throughout the observation period in migrants. The probability of late presentation for care clearly decreased in men who have sex with men (MSM) from 60% in 1999 to 45% in 2010. CONCLUSIONS: In Germany, the numbers of late presenters for HIV diagnosis and care remain high. The probability of late presentation for HIV diagnosis seems to be particularly high for migrants. These results argue in favour of targeted test promotion rather than opt-out screening. Late presentation for care seems to be an additional problem after HIV diagnosis. PMID- 22093173 TI - White gel pen easily marks a port-wine stain margin during pulsed dye laser therapy. PMID- 22093174 TI - Effects of SLC10A2 variant rs9514089 on gallstone risk and serum cholesterol levels- meta-analysis of three independent cohorts. AB - BACKGROUND: Recently, a single nucleotide polymorphism (SNP) rs9514089 in SLC10A2 (apical sodium-dependent bile acid transporter gene) has been identified as a susceptibility variant for cholelithiasis in humans. METHODS: Here we assessed the effects of rs9514089 on gallstone risk and related phenotypes of the metabolic syndrome in the self-contained population of Sorbs (183 cases with gallstones/826 controls). Furthermore, we performed a meta-analysis for effects of rs9514089 on susceptibility for cholelithiasis in three independent cohorts (Stuttgart: 56 cases/71 controls, Aachen: 184 cases/184 controls and Sorbs). RESULTS: There was no significant association of rs9514089 with gallstone risk, serum lipid parameters and BMI in the Sorbs and in the meta-analysis of all three cohorts (p > 0.05). There was an effect trend in the subgroup of lean subjects but based on different effect directions in the three cohorts there was no significant association in the meta-analysis. CONCLUSIONS: We were not able to replicate the effect of rs9514089 on gallstone risk in the Sorbs. Further analyses in larger cohorts are required to finally assess the role of genetic variants in SLC10A2 in human gallstone development and lipid metabolism. PMID- 22093175 TI - The contribution of protein kinase C and CPI-17 signaling pathways to hypercontractility in murine experimental colitis. AB - BACKGROUND: Colonic smooth muscle contractility is altered in colitis, and several protein kinase pathways can mediate colonic smooth muscle contraction. In the present study, we investigated whether protein kinase C (PKC) pathways also play a role in colonic hypercontractility observed during T(H) 2 colitis in BALB/c mice. METHODS: Colitis was induced in BALB/c mice by provision of 5% dextran sodium sulfate (DSS) for 7 days. Changes in smooth muscle contractility were examined using dissected circular smooth muscle preparations from the distal colon. The contribution of conventional and novel PKC isozymes to the hypercontractile response was examined with pharmacological PKC inhibitors. Western blot analyses were used to examine protein expression and phosphorylation changes. KEY RESULTS: Colonic smooth muscle was associated with inflammation induced hypercontractility and altered PKC expression. Carbachol-induced peak (phasic) and sustained (tonic) contractions were increased. Chelerythrine was the most effective PKC inhibitor of both phasic and tonic contractions. There was no general difference in the percent contribution of conventional and novel PKC isozymes toward the DSS-induced hypercontractility, but inhibition of sustained force with GF109203x was higher for inflamed muscle. The CPI-17 phosphorylation was equally suppressed in both normal and DSS conditions by Go6976 and chelerythrine, but only for the phasic component of contraction. CONCLUSIONS & INFERENCES: The outcomes suggest that both conventional and novel PKC isozymes contribute to the phasic and tonic contractile components of BALB/c colonic circular smooth muscle under normal conditions, with novel PKC isozymes having a greater contribution to the tonic contraction. However, no effect of inflammation was observed on the relative contribution of PKC and CPI-17 toward the observed hypercontractility. PMID- 22093176 TI - Low-fluence Q-switched 1,064-nm neodymium-doped yttrium aluminum garnet laser for the treatment of facial partial unilateral lentiginosis in Koreans. AB - BACKGROUND: Established pigment lasers have been used in partial unilateral lentiginosis (PUL) have shown unsatisfactory results. OBJECTIVE: To determine the effectiveness and safety of low-fluence 1,064-nm Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG) laser treatment of PUL in Koreans. MATERIALS AND METHODS: Ten Korean patients with facial PUL were treated with 1,064-nm QS Nd:YAG laser, 7-mm spot size, 1.5- to 2.5-J/cm(2) fluence at 2-week intervals. Standard digital photographs were taken under the same condition at baseline and at each follow-up visit. Independent dermatologists evaluated the photographs. All patients completed a questionnaire to assess their subjective satisfaction with the laser treatment using a 5-point grading system. Degree of pain was assessed using a visual analog scale (0-10). Any complications and side effects were recorded at each visit. Patients were followed up every 4 weeks for 12 weeks after the last laser treatment. RESULTS: Five of 10 patients (50%) had achieved excellent improvement (76-100%) at the end of treatment, and the remaining 50% had good improvement (51-75%). In patient self-evaluation of the degree of improvement of PUL, nine (90%) assessed it as very much to much improved (>50% improvement), and 1 (10%) assessed it as moderate (50-75%). Subjects rated the pain associated with laser treatment at a mean score of 3.3 (range: 1-5) on a scale of 1 to 10. Mottled hypopigmentation developed in two patients. At follow up, 12 weeks after the last laser session, all of the patients had partial recurrence, which wqw resolved with one to two sessions of laser treatment. CONCLUSION: Low-fluence 1,064-nm QS Nd:YAG laser treatment for facial PUL in Koreans showed improvement with no significant side effects. We recommend the low fluence 1,064-nm QS Nd:YAG laser as a treatment option for facial PUL. PMID- 22093177 TI - New classification for men with lower urinary tract symptoms: cluster analysis using the International Prostate Symptom Score. AB - SUBJECTS AND METHODS: * Secondary analysis of anonymous data from 10,434 patients enrolled in a postmarketing surveillance study of tamsulosin in Japan was performed. Data were prospectively collected through the central register from men diagnosed with LUTS in 1100 medical institutions between October 2004 and March 2005. * Those who had received an alpha1-adrenoceptor antagonist within 1 week before the initial visit were excluded. * The survey items were International Prostate Symptom Score (IPSS), quality of life (QOL) score, and patient characteristics including age, bodyweight, body mass index, and LUTS related comorbid conditions. * Data on IPSS items were used in a hierarchical cluster analysis (Ward's method). RESULTS: * Of 10,434 men with LUTS, 9910 were included in the analysis after 5% data trimming (524 patients). Five symptom clusters were identified and the symptom types of each cluster were examined. * The largest cluster (27%) consisted of patients with multiple severe symptoms, i.e. complaining of six or more symptoms with a mean score >=2.8. In contrast, the second smallest cluster (13%) consisted of patients with minimal symptoms, i.e. complaining of essentially one or two symptom with a mean score <=2.1. * The other three clusters were labelled based on their dominant symptoms. The clusters were weak stream (27%), storage symptoms (21%) and voiding symptoms (12%). * The storage symptoms group was older, and had more comorbidities. * The distribution of the QOL score was different among the clusters, and the percentage of patients who were very dissatisfied was highest in the multiple severe symptoms group and lowest in the minimal symptoms group. CONCLUSIONS: * Cluster analysis using the IPSS showed that men with LUTS can be classified into five characteristic symptom groups. * A new approach to symptom-based classification may be useful to elucidate the pathology of male LUTS and individualize the therapeutic strategy for affected patients, but further studies are needed. PMID- 22093178 TI - Determining the safety of office-based surgery: what 10 years of Florida data and 6 years of Alabama data reveal. AB - BACKGROUND: This is a continued examination of 10 years of prospectively collected Florida in-office adverse event data and new comparable data from mandatory Alabama in-office adverse event data reporting. OBJECTIVE: To determine which office surgical procedures have resulted in reported complications. METHODS: This study is a compilation of mandatory reporting of office surgical complications by Florida and Alabama physicians to a central agency. Reports resulting in death or a hospital transfer were further investigated over the telephone or on-line to determine the reporting physician's board certification status, hospital privilege status, and office accreditation status. RESULTS: In 10 years in Florida, there were 46 deaths and 263 procedure-related complications and hospital transfers; 56.5% (26/46) of deaths and 49.8% (131/263) of hospital transfers were associated with non-medically necessary (cosmetic) procedures. The majority of deaths (67%) and hospital transfers (74%) related to non-medically necessary (cosmetic) procedures were from procedures performed on patients under general anesthesia. Liposuction and liposuction with abdominoplasty or other cosmetic procedure resulted in 10 deaths and 34 hospital transfers. Thirty-eight percent of offices reporting adverse events were accredited by an independent accrediting agency, 93% of physicians were board certified, and 98% of physicians had hospital privileges. The most common specialty of physicians reporting adverse events was plastic surgery (45% of all reported complications). Dermatologists reported four total complications (no deaths) and accounted for 1.3% of all complications over the 10-year period. In 6 years in Alabama, there were three deaths and 49 procedure-related complications and hospital transfers; 42% (22/52) of hospital transfers and no deaths were associated with non medically necessary (cosmetic) procedures. The majority of hospital transfers related to cosmetic procedures (86%) were from procedures performed on patients under general anesthesia. Liposuction accounted for no deaths and two hospital transfers. Seventy-one percent of offices reporting adverse events were accredited by an independent accrediting agency, and 100% of physicians were board-certified. Plastic surgery was the most common specialty represented in adverse event reporting (42.3% of all reported complications). Dermatologists reported one complication (no deaths) and accounted for 1.9% of all complications over the 6-year period. CONCLUSIONS: Continued analysis reveals that medically necessary office surgery does not represent an emergent hazard to patients. The data obtained from 10 and 6 years of adverse event reporting in Florida and Alabama, respectively, are comparable and consistent. Medically necessary surgical procedures performed in the office setting by dermatologists have an exceedingly low complication rate, and complications that arose were largely unexpected, isolated, and possibly unpreventable. Cosmetic procedures performed in offices by dermatologists under local and dilute local anesthesia yielded no reported complications. Complications from cosmetic procedures accounted for nearly half of all reported incidents in Florida and Alabama, and in both states, plastic surgeons were most represented in adverse event reports. Liposuction performed under general anesthesia requires further investigation because deaths from this procedure continue to occur despite the ability to use dilute local anesthesia for this procedure. Requiring physician board certification and physician hospital privileges does not seem to increase safety of patients undergoing surgical procedures in the office setting. Mandatory reporting of adverse events in the office setting should continue to be championed. Reporting of delayed deaths after hospital outpatient and ambulatory surgery center procedures should be implemented. All data should be made available for scientific analysis after protecting patient confidentiality. PMID- 22093179 TI - Low-level tacrolimus-based immunosuppression and polyomavirus BK surveillance in renal transplant patients. PMID- 22093180 TI - Emotional problems in preadolescents in Norway: the role of gender, ethnic minority status, and home- and school-related hassles. AB - BACKGROUND: "The gender gap" refers to a lifelong higher rate of emotional problems in girls, as compared to boys, that appears during adolescence. The gender gap is a well-replicated finding among older adolescents and is assumed to be a cross-cultural phenomenon. However, these cross-cultural studies have not investigated the gender gap in ethnic minorities but sampled ethnic majority adolescents in different countries. Some studies that investigated the gender gap across ethnic groups indirectly (by presenting emotional problem scores stratified by gender and ethnic group) indicate that the gender gap is less prominent or even absent among minorities. The aims of this study were to assess whether the gender gap is found in both majority and minority preadolescents, and to investigate whether a possible (gender and ethnic) group difference can be accounted for by differences in home or school hassles. METHODS: Participants were 902 preadolescent students (aged 10 to 12) from two cities in Norway. We collected self-report measures of emotional problems and home and school hassles. Using mediated moderation analysis we tested whether the interaction effect between gender and ethnic minority background on emotional problems was mediated by home or school hassles. RESULTS: The gender gap in emotional problems was restricted to ethnic majority preadolescents. School hassles but not home hassles accounted in part for this effect. CONCLUSIONS: The absence of the gender gap among minority as opposed to majority preadolescents may indicate that social circumstances may postpone or hamper the emergence and magnitude of the gender gap in ethnic minority preadolescents. In this study, school hassles partly accounted for the combined gender and ethnic group differences on emotional problems. This indicates that school hassles may play a role in the higher levels of emotional problems in preadolescent minority boys and consequently the absence of a gender gap found in our minority sample. PMID- 22093181 TI - Insulin augments tumor necrosis factor-alpha stimulated expression of vascular cell adhesion molecule-1 in vascular endothelial cells. AB - BACKGROUND: Atherosclerosis is an inflammatory disease that is marked by increased presence of Tumor Necrosis Factor-alpha (TNFalpha), increased expression of Vascular Cell Adhesion Molecule-1 (VCAM-1), increased presence of serum monocytes and activation of the canonical inflammatory molecule, Nuclear Factor Kappa-B (NFkappaB). Hyperinsulinemia is a hallmark of insulin resistance and may play a key role in this inflammatory process. METHODS: Using Western blot analysis, immunocytochemistry, flow cytometry and biochemical inhibitors, we measured changes in VCAM-1 protein expression and NFkappaB translocation in vascular endothelial cells in the presence of TNFalpha and/or hyperinsulinemia and in the absence or presence of kinase pathway inhibitors. RESULTS: We report that hyperinsulinemia augmented TNFalpha stimulated increases in VCAM-1 protein greater than seen with TNFalpha alone and decreased the time in which VCAM-1 translocated to the cell surface. We also observed that in the presence of Wortmannin, a biochemical inhibitor of phosphatidylinositol 3-kinase (a hallmark of insulin resistance), VCAM-1 expression was greater in the presence of TNFalpha plus insulin as compared to that seen with insulin or TNFalpha alone. Additionally, nuclear import of NFkappaB occurred sooner in the presence of insulin and TNFalpha together as compared to each alone, and in the presence of Wortmannin, nuclear import of NFkappaB was greater than that seen with insulin and TNFalpha alone. CONCLUSIONS: hyperinsulinemia and insulin resistance appear to augment the inflammatory effects of TNFalpha on VCAM-1 expression and NFkappaB translocation, both of which are markers of inflammation in the vasculature. PMID- 22093183 TI - Production of 61Cu using natural cobalt target and its separation using ascorbic acid and common anion exchange resin. AB - (61)Cu was produced by (nat)Co(alpha, xn)(61)Cu reaction. (61)Cu production yield was 89.5 MBq/MUAh (2.42 mCi/MUAh) at the end of irradiation (EOI). A simple radiochemical separation method using anion exchange resin and ascorbic acid has been employed to separate the product radionuclide from inactive target material and co-produced non-isotopic impurities. The radiochemical separation yield was about 90%. Radiochemical purity of (61)Cu was >99% 1 h after EOI. Final product was suitable for making complex with N(2)S(2) type of ligands. PMID- 22093182 TI - The MATRICS Consensus Cognitive Battery (MCCB): clinical and cognitive correlates. AB - The purpose of this study was to examine the cognitive and clinical correlates of the MATRICS Consensus Cognitive Battery (MCCB) which was originally developed to be an endpoint for cognitive enhancement clinical trials. In a sample of 117 people with schizophrenia and 77 healthy control participants we found the following: a) the MCCB was highly sensitive to the type and level of impairment typically observed in schizophrenia, b) the MCCB composite score was highly correlated with WASI Estimated Full Scale IQ score, c) that the MCCB domain scores were generally moderately-highly intercorrelated, d) that MCCB performance was minimally related to clinical symptom type and severity, and e) the MCCB is sensitive to employment status with better performance in employed vs. unemployed patients. These data support the validity of the MCCB as a sensitive measure of cognitive impairment in schizophrenia and suggest that MCCB performance is relevant for functional outcome. The data also suggest that the MCCB domain scores may offer limited resolution on discrete cognitive functions. PMID- 22093184 TI - Formation of repressor-inducer-operator ternary complex: negative cooperativity of d-camphor binding to CamR. AB - A repressor composed of homodimeric subunits, as is often found in bacteria, possesses two effector-binding sites per molecule, enabling sophisticated regulation by the cooperative binding of two effector molecules. Positive cooperativity generates a narrower region of effector concentration for switching, but little is known about the role of negative cooperativity. d camphor, an inducer for Pseudomonas putida cytochrome P450cam hydroxylase operon (camDCAB), binds to the homodimeric cam repressor (CamR). Here, we report solid evidence that the complex of CamR and an operator DNA is not dissociated by the first binding of d-camphor but, at a higher concentration, is dissociated by the second binding. d-camphor thus binds to the CamR in two steps with negative cooperativity, yielding two distinct dissociation constants of K(d1 ) =( ) 0.064 +/- 0.030 and K(d2 ) =( ) 14 +/- 0.3 MUm, as well as the Hill coefficient of 0.56 +/- 0.05 (<1). The first binding guarantees the high specificity of the inducer by the high affinity, although the second binding turns on the gene expression at a 200-fold higher concentration, a more suitable switching point for the catabolism of d-camphor. PMID- 22093185 TI - Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid. AB - Maternal use of valproic acid (VPA) during pregnancy has been implicated in the aetiology of autism spectrum disorders in children, and rodents prenatally exposed to VPA showed behavioural alterations similar to those observed in humans with autism. However, the exact mechanism for VPA-induced behavioural alterations is not known. To study this point, we examined the effects of prenatal exposure to VPA and valpromide, a VPA analog lacking histone deacetylase inhibition activity, on behaviours, cortical pathology and histone acetylation levels in mice. Mice exposed to VPA at embryonic day 12.5 (E12.5), but not at E9 and E14.5, displayed social interaction deficits, anxiety-like behaviour and memory deficits at age 4-8 wk. In contrast to male mice, the social interaction deficits (a decrease in sniffing behaviour) were not observed in female mice at age 8 wk. The exposure to VPA at E12.5 decreased the number of Nissl-positive cells in the middle and lower layers of the prefrontal cortex and in the lower layers of the somatosensory cortex at age 8 wk. Furthermore, VPA exposure caused a transient increase in acetylated histone levels in the embryonic brain, followed by an increase in apoptotic cell death in the neocortex and a decrease in cell proliferation in the ganglionic eminence. In contrast, prenatal exposure to valpromide at E12.5 did not affect the behavioural, biochemical and histological parameters. Furthermore, these findings suggest that VPA-induced histone hyperacetylation plays a key role in cortical pathology and abnormal autism-like behaviours in mice. PMID- 22093186 TI - Prediction of hospital acute myocardial infarction and heart failure 30-day mortality rates using publicly reported performance measures. AB - OBJECTIVE: To identify an approach to summarizing publicly reported hospital performance data for acute myocardial infarction (AMI) or heart failure (HF) that best predicts current year hospital mortality rates. SETTING: A total of 1,868 U.S. hospitals reporting process and outcome measures for AMI and HF to the Centers for Medicare and Medicaid Services (CMS) from July 2005 to June 2006 (Year 0) and July 2006 to June 2007 (Year 1). DESIGN: Observational cohort study measuring the percentage variation in Year 1 hospital 30-day risk-adjusted mortality rate explained by denominator-based weighted composite scores summarizing hospital Year 0 performance. DATA COLLECTION: Data were prospectively collected from hospitalcompare.gov. RESULTS: Percentage variation in Year 1 mortality was best explained by mortality rate alone in Year 0 over other composites including process performance. If only Year 0 mortality rates were reported, and consumers using hospitals in the highest decile of mortality instead chose hospitals in the lowest decile of mortality rate, the number of deaths at 30 days that potentially could have been avoided was 1.31 per 100 patients for AMI and 2.12 for HF (p < .001). CONCLUSION: Public reports focused on 30-day risk-adjusted mortality rate may more directly address policymakers' goals of facilitating consumer identification of hospitals with better outcomes. PMID- 22093187 TI - Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. AB - BACKGROUND: Bone metastases are a major cause of morbidity and mortality in men with prostate cancer. Preclinical studies suggest that osteoclast inhibition might prevent bone metastases. We assessed denosumab, a fully human anti-RANKL monoclonal antibody, for prevention of bone metastasis or death in non-metastatic castration-resistant prostate cancer. METHODS: In this phase 3, double-blind, randomised, placebo-controlled study, men with non-metastatic castration resistant prostate cancer at high risk of bone metastasis (prostate-specific antigen [PSA] >=8.0 MUg/L or PSA doubling time <=10.0 months, or both) were enrolled at 319 centres from 30 countries. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous denosumab 120 mg or subcutaneous placebo every 4 weeks. Randomisation was stratified by PSA eligibility criteria and previous or ongoing chemotherapy for prostate cancer. Patients, investigators, and all people involved in study conduct were masked to treatment allocation. The primary endpoint was bone-metastasis-free survival, a composite endpoint determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause. Efficacy analysis was by intention to treat. The masked treatment phase of the trial has been completed. This trial was registered at ClinicalTrials.gov, number NCT00286091. FINDINGS: 1432 patients were randomly assigned to treatment groups (716 denosumab, 716 placebo). Denosumab significantly increased bone-metastasis-free survival by a median of 4.2 months compared with placebo (median 29.5 [95% CI 25.4-33.3] vs 25.2 [22.2-29.5] months; hazard ratio [HR] 0.85, 95% CI 0.73-0.98, p=0.028). Denosumab also significantly delayed time to first bone metastasis (33.2 [95% CI 29.5-38.0] vs 29.5 [22.4-33.1] months; HR 0.84, 95% CI 0.71-0.98, p=0.032). Overall survival did not differ between groups (denosumab, 43.9 [95% CI 40.1-not estimable] months vs placebo, 44.8 [40.1-not estimable] months; HR 1.01, 95% CI 0.85-1.20, p=0.91). Rates of adverse events and serious adverse events were similar in both groups, except for osteonecrosis of the jaw and hypocalcaemia. 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo. Hypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%) on placebo. INTERPRETATION: This large randomised study shows that targeting of the bone microenvironment can delay bone metastasis in men with prostate cancer. FUNDING: Amgen Inc. PMID- 22093188 TI - Treatment of prostate cancer metastases: more than semantics. PMID- 22093189 TI - Distribution and associations of [-2]proenzyme-prostate specific antigen in community dwelling black and white men. AB - PURPOSE: We provide cross-sectional normative data on [-2]proenzyme-prostate specific antigen from the Olmsted County Study of Urinary Symptoms and Health Status among Men, and the Flint Men's Health Study. We also describe associations with clinical urological measures and the risk of prostate cancer diagnosis. MATERIALS AND METHODS: Measurements of [-2]proenzyme-prostate specific antigen were obtained from 420 white men from Olmsted County, Minnesota, and 328 black men from Genesee County, Michigan. Cross-sectional associations between [ 2]proenzyme-prostate specific antigen and prostate enlargement/elevated prostate specific antigen were assessed. Cox proportional hazard models were used to assess associations between [-2]proenzyme-prostate specific antigen and the incident diagnosis of prostate cancer. RESULTS: Baseline [-2]proenzyme-prostate specific antigen was slightly higher in black men at a median of 6.3 pg/ml (25th, 75th percentiles 4.1, 8.9) than in white men at a median of 5.6 pg/ml (25th, 75th percentiles 3.9, 7.7, respectively, p = 0.01). Baseline [-2]proenzyme-prostate specific antigen was highly predictive of biopsy confirmed prostate cancer in the Olmsted County Study cohort. Relative to men in the [-2]proenzyme-prostate specific antigen lower quartile those in the upper quartile were at almost eightfold increased risk for prostate cancer (HR 7.8, 95% CI 2.2-27.8) after adjusting for age and baseline prostate specific antigen. CONCLUSIONS: In these cohorts of community dwelling black and white men [-2]proenzyme-prostate specific antigen was much lower than in previous studies. These data suggest that [ 2]proenzyme-prostate specific antigen may help identify prostate cancer in men with serum prostate specific antigen in an indeterminate range, although the reference ranges for white and black men may differ slightly. PMID- 22093190 TI - Benign prostate specific antigen distribution and associations with urological outcomes in community dwelling black and white men. AB - PURPOSE: We describe cross-sectional associations of benign prostate specific antigen with clinical urological measures and examined the risk of future urological outcomes in 2 population based cohorts of black and white men, respectively. MATERIALS AND METHODS: Two population based cohort studies were established to characterize the natural history of and risk factors for prostate disease progression in white and black male residents of Olmsted County, Minnesota, and Genesee County, Michigan, respectively. RESULTS: The benign prostate specific antigen distribution was similar in black men at a median of 32.9 pg/ml (25th, 75th percentiles 17.3, 68.0) and white men at a median of 32.2 pg/ml (25th, 75th percentiles 16.6, 68.9, respectively). However, it was much lower than in previous reports. For Olmsted County men in the upper quartile of benign prostate specific antigen there was a fifteenfold increased risk of prostate cancer (HR 14.6, 95% CI 3.1-68.6) and a twofold higher risk of treatment for benign prostatic hyperplasia (HR 2.2, 95% CI 1.2-4.2) after adjusting for age. After additional adjustment for baseline prostate specific antigen the association between benign prostate specific antigen and prostate cancer risk was attenuated but remained almost ninefold higher for men in the upper quartile of benign prostate specific antigen (HR 8.7, 95% CI 1.8-42.4). The twofold higher risk of treatment for benign prostatic hyperplasia also remained after adjusting for baseline prostate specific antigen for men in the upper benign prostate specific antigen quartile (HR 1.9, 95% CI 0.9-4.0). CONCLUSIONS: Results suggest that increased benign prostate specific antigen may help identify men with prostate cancer and those at risk for benign prostatic hyperplasia treatment. PMID- 22093191 TI - Time for a change: dynamic urban ecology. AB - Contemporary cities are expanding rapidly in a spatially complex, non-linear manner. However, this form of expansion is rarely taken into account in the way that urbanization is classically assessed in ecological studies. An explicit consideration of the temporal dynamics, although frequently missing, is crucial in order to understand the effects of urbanization on biodiversity and ecosystem functioning in rapidly urbanizing landscapes. In particular, a temporal perspective highlights the importance of land-use legacies and transient dynamics in the response of biodiversity to environmental change. Here, we outline the essential elements of an emerging framework for urban ecology that incorporates the characteristics of contemporary urbanization and thus empowers ecologists to understand and intervene in the planning and management of cities. PMID- 22093192 TI - A prospective study of pelvic floor dysfunctions related to delivery. AB - OBJECTIVE: To estimate the prevalence and impact on quality of life of urinary incontinence (UI) and anal incontinence (AI) three months after first delivery; to identify risk factors involved in UI or AI; to evaluate possible changes in sexual behaviour and anatomical modifications of pelvic floor after childbirth. STUDY DESIGN: A multicenter prospective study, in six Italian Ob/Gyn departments, of nulliparous women who delivered at term (37-42 weeks of gestation) between April and September 2005. A structured questionnaire investigated several maternal and obstetric variables. UI and AI were assessed by administration of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and according to Wexner's Continence Grading Scale, at 2-3 days post-partum and at 3 months after delivery. Changes in sexual behaviour, and pelvic floor condition after delivery, were also recorded. Statistical analysis included comparison of means (Mann-Whitney or Student's t-test) and proportions (Chi square test). Multiple logistic regression analysis was performed including variables that were significant in univariate comparisons. RESULTS: Of 960 enrolled women, 744 were evaluated 3 months after delivery and included in final analysis. The prevalences of UI and AI at that time were 21.6% and 16.3%, respectively. Onset of incontinence during pregnancy was an independent predictor for persistent UI (Odds Ratio (OR) 4.6, Confidence Interval (CI) 3.1-6.8, p<0.001) and AI (OR 3.6, CI 2.2-6.1, p<0.001). Family history of urinary or anal incontinence were respectively associated with UI (OR 2.6, CI 1.6-4.0, p<0.001) and AI (OR 2.4, CI 1.4-4.0, p<0.001) 3 months after delivery. Among obstetric factors, vaginal delivery was a strong risk factor for UI (OR 3.3, CI 2.0-5.3, p<0.001). The sexual score improved 3 months after delivery in 72.4% of women. Urogynaecological evaluation showed a significant association between grade 1-2 anterior prolapse, urethral hypermobility and UI. CONCLUSION: New onset of UI or AI during pregnancy, positive family history and vaginal delivery are independent risk factors for the persistence of symptoms of UI and AI in the early postpartum period. Adequate counselling and the implementation of targeted strategies to prevent or early identify these conditions are therefore mandatory to improve the patient's quality of life. PMID- 22093193 TI - Heart failure and diabetes: time to pay attention. PMID- 22093194 TI - LV twisting and untwisting in HCM: ejection begets filling. Diastolic functional aspects of HCM. AB - Conventional and emerging concepts on mechanisms by which hypertrophic cardiomyopathy (HCM) engenders diastolic dysfunction are surveyed. A shift from familiar left ventricular (LV) diastolic function approaches to large-scale (twist-untwist) and small-scale (titin unfolding-refolding, etc.) wall rebound models, incorporating interaction and dynamic distortions and rearrangements of myofiber sheets and ultrastructural constituents, is suggested. Such an emerging new paradigm of diastolic dynamics, emphasizing the relationship of myofiber sheet and ultraconstituent distortion to LV mechanics and end-systolic shape, might clarify intricate patterns of early diastolic rebound and suction, needed for LV filling in many of the polymorphic phenotypes of HCM. PMID- 22093195 TI - The fixed-dose combination drug for secondary cardiovascular prevention project: improving equitable access and adherence to secondary cardiovascular prevention with a fixed-dose combination drug. Study design and objectives. AB - In spite of advances in prevention and treatment, the burden of cardiovascular diseases is increasing. A fixed-dose combination (FDC) pill, or "polypill," composed of evidence-based drugs has been proposed as a means of improving cardiovascular prevention by reducing cost and increasing patient adherence to treatment. The aim of the FOCUS project, funded by the 7th Framework Programme of the European Commission, is to characterize the factors that underlie inadequate secondary prevention and to test a new FDC. To achieve these goals, a 9-member consortium has been constituted, including institutions from Argentina, France, Italy, Spain, and Switzerland. FOCUS Phase-1 will examine factors potentially related to lack of adequate secondary prevention in 4,000 post-myocardial infarction (MI) patients and analyze the relationship between these factors and patient treatment adherence. Primary end points will be (1) the percentage of patients receiving aspirin, angiotensin-converting enzyme inhibitors, and statins and (2) adherence to treatment measured by the Morisky-Green test. FOCUS Phase-2 is a randomized trial that will compare adherence to treatment in 1,340 post myocardial infarction patients either receiving an FDC comprising aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and simvastatin (40 mg) or receiving the same 3 drugs separately. PMID- 22093196 TI - The design and rationale of the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study. AB - OBJECTIVES: Saxagliptin, a dipeptidyl peptidase 4 inhibitor, improves glycemic control in patients with type 2 diabetes mellitus (T2DM) by increasing endogenous active, intact glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in response to food, which augments insulin secretion and decreases glucagon release. RESEARCH DESIGN AND METHODS: SAVOR-TIMI 53 is a phase 4, randomized, double-blind, placebo-controlled trial conducted in 25 countries that is designed to evaluate the safety and efficacy of saxagliptin during long-term treatment of approximately 16,500 patients with T2DM. Eligible patients who are either treatment naive or on any background antidiabetic treatment (except incretin therapy) with history of established cardiovascular (CV) disease or multiple risk factors are randomized 1:1 to saxagliptin 5 mg QD (2.5 mg in subjects with moderate/severe renal impairment) or matching placebo, stratified by qualifying disease state. The primary end point is the composite of CV death, nonfatal myocardial infarction, or nonfatal ischemic stroke. The trial will continue until approximately 1,040 primary end points accrue, providing 85% power to identify a 17% relative reduction of the primary end point with saxagliptin versus placebo and 98% power to test for noninferiority of saxagliptin versus placebo (reject the upper limit of 95% CI for a hazard ratio <1.3 at a 1-sided alpha of .025). CONCLUSION: SAVOR-TIMI 53 is testing the hypothesis that treatment with saxagliptin is safe and reduces CV events in high-risk patients with T2DM. PMID- 22093197 TI - Rationale and design of the MASS COMM trial: A randomized trial to compare percutaneous coronary intervention between MASSachusetts hospitals with cardiac surgery on-site and COMMunity hospitals without cardiac surgery on-site. AB - BACKGROUND: Emergency surgery has become an increasingly rare event after percutaneous coronary intervention (PCI). There have been no randomized trials evaluating whether cardiac surgery services on-site are essential for patient safety and optimal outcomes during and after PCI. STUDY DESIGN: The MASS COMM trial (ClinicalTrials.gov no. NCT01116882) is a randomized trial comparing the safety and effectiveness of nonemergency PCI at hospitals without surgery on-site (SOS) (non-SOS hospitals) and hospitals with SOS (SOS hospitals). A total of 3,690 subjects will be randomized in a 3:1 fashion to undergo PCI at non-SOS and SOS hospitals, with follow-up at hospital discharge, 30 days, and 12 months after PCI. The rate of major adverse cardiac events (all-cause mortality, myocardial infarction, repeat revascularization, and stroke) will serve as the primary safety end point at 30 days and the primary effectiveness end point at 12 months. The design is a 1-way randomized trial with a statistical hypothesis of noninferiority of nonemergency PCI at non-SOS hospitals for both safety and effectiveness end points. CONCLUSIONS: This multicenter, randomized trial will compare the relative safety and effectiveness of nonemergency PCI at sites with and without cardiac SOS. PMID- 22093198 TI - The first call from Dad. PMID- 22093199 TI - Should all patients be treated with an angiotensin-converting enzyme inhibitor after coronary artery bypass graft surgery? The impact of angiotensin-converting enzyme inhibitors, statins, and beta-blockers after coronary artery bypass graft surgery. AB - BACKGROUND: We sought to evaluate the association between angiotensin-converting enzyme (ACE) inhibitors and outcomes after coronary artery bypass graft surgery (CABG). METHODS: Postoperative outpatient utilization of ACE inhibitors, statins, and beta-blockers was assessed in a cohort of 3,718 patients after CABG 65 years and older. The primary outcome was freedom from a composite of all-cause mortality or hospital readmission for cardiac events or procedures. RESULTS: Use of all 3 medication classes increased significantly over the study period. Female patients and patients with a history of myocardial infarction, diabetes, and poor left ventricular function were independently associated with ACE inhibitor use on multivariate analysis (all P < .05). At a median follow-up of 3 years, postoperative therapy with an ACE inhibitor had no effect on death or rehospitalization for cardiovascular events (adjusted hazard ratio [HR] 1.12, 95% CI 0.96-1.30, P = .16). However, statins (HR 0.65, 95% CI 0.57-0.74, P < .0001) and beta-blockers (HR 0.83, 95% CI 0.74-0.93, P = .001) were associated with a significantly improved event-free survival. CONCLUSIONS: Among patients after CABG 65 years or older, ACE inhibitors had no independent effect on mortality or recurrent ischemic events in the midterm after CABG, although a benefit was observed for statins and beta-blockers. PMID- 22093200 TI - Treatment with adenosine diphosphate receptor inhibitors-longitudinal assessment of treatment patterns and events after acute coronary syndrome (TRANSLATE-ACS) study design: expanding the paradigm of longitudinal observational research. AB - BACKGROUND: Platelet inhibition is critical in reducing both short- and long-term atherothrombotic risks after acute myocardial infarction (MI), especially among patients managed with percutaneous coronary intervention (PCI). Currently available antiplatelet medications, including adenosine diphosphate (ADP) receptor inhibitors, have demonstrated variability in efficacy and safety in clinical trials, yet few studies have examined contemporary "real-world" approaches to platelet inhibition and associated outcomes. METHODS: TRANSLATE-ACS is a prospective observational study that will track up to 17,000 MI patients managed with PCI, from the inhospital to outpatient settings for up to 12 months postdischarge to provide a comprehensive picture of current treatment patterns and outcomes in routine clinical practice. TRANSLATE-ACS exemplifies a collaborative study design that efficiently builds upon a well-established PCI registry platform, and yet, through a systematic telephone interview follow-up process, provides important longitudinal clinical and economic follow-up capacity through 15 months after initial MI hospitalization. Furthermore, TRANSLATE-ACS incorporates a hospital-level, clustered, randomized substudy to investigate the impact of point-of-care platelet inhibition testing on subsequent patient management. Finally, TRANSLATE-ACS provides feedback through quarterly reports to participating sites on their care practices benchmarked to peer performance to support and promote longitudinal quality of cardiovascular care delivery. CONCLUSION: TRANSLATE-ACS not only addresses important clinical and scientific questions but also includes pioneering design features that will assist in the evolution of clinical registries. PMID- 22093202 TI - Cognitive impairment and outcomes in older adult survivors of acute myocardial infarction: findings from the translational research investigating underlying disparities in acute myocardial infarction patients' health status registry. AB - BACKGROUND: Cognitive impairment without dementia (CIND) and acute myocardial infarction (AMI) are prevalent in older adults; however, the association of CIND with outcomes after AMI is unknown. METHODS: We used a multicenter registry to study 772 patients >=65 years with AMI, enrolled between April 2005 and December 2008, who underwent cognitive function assessment with the Telephone Interview for Cognitive Status-modified (TICS-m) 1 month after AMI. Patients were categorized by cognitive status to describe characteristics and in-hospital treatment, including quality of life and survival 1 year after AMI. RESULTS: Mean age was 73.2 +/- 6.3 years; 58.5% were men, and 78.2% were white. Normal cognitive function (TICS-m >22) was present in 44.4%; mild CIND (TICS-m 19-22) in 29.8%; and moderate/severe CIND (TICS-m <19) in 25.8% of patients. Rates of hypertension (72.6%, 77.4%, and 81.9%), cerebrovascular accidents (3.5%, 7.0%, and 9.0%), and myocardial infarction (20.1%, 22.2%, and 29.6%) were higher in those with lower TICS-m scores (P < .05 for comparisons). AMI medications were similar by cognitive status; however, CIND was associated with lower cardiac catheterization rates (P = .002) and cardiac rehabilitation referrals (P < .001). Patients with moderate/severe CIND had higher risk-adjusted 1-year mortality that was nonstatistically significant (adjusted hazard ratio 1.97, 95% CI 0.99-3.94, P = .054; referent normal, TICS-m >22). Quality of life across cognitive status was similar at 1 year. CONCLUSIONS: Most older patients surviving AMI have measurable CIND. Cognitive impairment without dementia was associated with less invasive care, less referral and participation in cardiac rehabilitation, and worse risk adjusted 1-year survival in those with moderate/severe CIND, making it an important condition to consider in optimizing AMI care. PMID- 22093203 TI - Effect of esomeprazole versus famotidine on platelet inhibition by clopidogrel: a double-blind, randomized trial. AB - BACKGROUND: Previous studies showed that esomeprazole does not interfere significantly with the platelet inhibitory effect of clopidogrel. It is unknown whether famotidine, a histamine 2 receptor antagonist, interacts with clopidogrel. This double-blind, randomized study aimed to compare the influence of esomeprazole and famotidine on the platelet inhibitory effect of clopidogrel. METHODS: Patients with acute coronary syndrome or elective percutaneous coronary interventions treated with aspirin and clopidogrel cotherapy were randomized to receive esomeprazole 20 mg daily or famotidine 40 mg daily. Platelet reactivity units (PRUs) were measured at baseline and on day 28. The primary analysis involved the PRU values on day 28. RESULTS: There were 44 patients in the esomeprazole group and 44 in the famotidine group. The baseline PRUs of the 2 groups were comparable (esomeprazole vs famotidine, 229.1 +/- 85.6 vs 220.4 +/- 83.0, P = .63). The PRUs on day 28 were 242.6 +/- 89.7 and 237.5 +/- 79.2 in the groups receiving esomeprazole and famotidine, respectively (mean difference 5.1, 95% CI -30.8 to 41.0, P = .78). CONCLUSIONS: The platelet inhibitory effect of clopidogrel was not significantly different between patients receiving esomeprazole and those receiving famotidine. Neither esomeprazole nor famotidine reduced the platelet inhibitory effect of clopidogrel. (Clinicaltrial.gov Identifier NCT01062516). PMID- 22093204 TI - Predicting long-term mortality in older patients after non-ST-segment elevation myocardial infarction: the CRUSADE long-term mortality model and risk score. AB - OBJECTIVES: We sought to develop a long-term mortality risk prediction model and a simplified risk score for use in older patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: Limited data are available regarding long-term mortality rates and concomitant risk predictors after acute myocardial infarction in contemporary community practice. METHODS: From the CRUSADE registry, a total of 43,239 (NSTEMI) patients aged >=65 years treated at 448 hospitals in the United States from 2003 to 2006 were linked to Centers for Medicare and Medicaid Services data to track longitudinal all-cause mortality (median follow-up 453 days). Cox proportional hazard modeling was used to determine baseline independent demographic, clinical, and laboratory variables associated with long-term mortality. A simplified long-term mortality risk score was subsequently developed from these results. RESULTS: The median age of this population was 77 years, and mortality rates at 1, 2, and 3 years were 24.4%, 33.2%, and 40.3%, respectively. We identified 22 variables independently associated with long-term mortality in a full model (c-statistic 0.754 in the derivation sample and 0.744 in the validation sample). The CRUSADE long-term mortality risk score was limited to the 13 most clinically and statistically significant variables from the full model yet retained comparable discrimination in the derivation and validation samples (c-statistics 0.734 and 0.727, respectively) and had good calibration across the risk spectra. CONCLUSIONS: Older patients face substantial long-term mortality risks after NSTEMI that can be accurately predicted from baseline characteristics. These prognostic estimates may support informed treatment decision-making and comparison of long-term provider outcomes. PMID- 22093205 TI - Safety and efficacy of adjusted-dose eptifibatide in patients with acute coronary syndromes and reduced renal function. AB - BACKGROUND: Dose adjustment of renally excreted antithrombotic drugs is recommended for patients with reduced renal function. We examined the influence of dose modification on bleeding and efficacy. METHODS: Based on initial study drug infusion rate, Early GP IIb/IIIa Inhibition in non-ST-segment elevation acute coronary syndromes (EARLY ACS) patients were categorized into groups: standard dose (2 MUg/kg/min; estimated creatinine clearance [eCrCl] >=50 ml/min), adjusted dose (1 MUg/kg/min; eCrCl <50 ml/min, per protocol), excess dose (2 MUg/kg/min; eCrCl <50 ml/min). We explored relationships among initial dosing, randomized treatment assignment, and bleeding and ischemic end points (96-h composite of death, myocardial infarction [MI], recurrent ischemia requiring urgent revascularization or thrombotic bailout, and 30-d death or MI). RESULTS: Of 8,708 patients with eCrCl and dosing data, 19% had eCrCl <50 ml/min. Of these, 13% received adjusted dose eptifibatide and 6% received an excess dose. Across all dosing groups, no significant reductions were found in ischemic end points between early versus delayed provisional eptifibatide (OR 1.14, 95% CI 0.80-1.65; OR 1.13, 95% CI 0.81-1.56, respectively, for 96-h and 30-d composite end points). Bleeding risk was not significantly increased in the early versus delayed provisional treatment group in either the adjusted (OR 1.50, 95% CI 0.95-2.39) or excess dose group (OR 1.67, 95% CI 0.85-3.39). There were no significant interactions between dose group and treatment strategy on bleeding or efficacy. CONCLUSION: Similar to observations in practice, despite guidelines recommendations and protocol guidance, 34% of EARLY ACS patients with reduced renal function failed to receive an appropriately adjusted study drug infusion. Use of an appropriately adjusted eptifibatide infusion was not associated with expected reductions in bleeding among patients with renal insufficiency. PMID- 22093206 TI - Myeloperoxidase in the diagnosis of acute coronary syndromes: the importance of spectrum. AB - BACKGROUND: Myeloperoxidase (MPO) is proposed for risk stratification in patients with suspected acute coronary syndromes (ACSs). We determined if MPO has diagnostic value in patients being evaluated for ACS. METHOD: MIDAS was an 18 center prospective study enrolling suspected ACS emergency department patients who presented <8 hours after symptom onset and in whom serial cardiac markers and objective cardiac perfusion testing were planned. Blinded MPO (Biosite, Inc, San Diego, CA) and troponin I (Triage Cardio 3; Biosite, Inc) were drawn at arrival, and Troponin I (TnI) was measured at 90, 180, and 360 minutes. Final diagnoses were adjudicated by the local investigator blinded to study assay. RESULTS: Of 1,018 patients, 54% were male, 26% black, with a mean age of 58 +/- 13 years. Diagnoses were ACS in 288 (23%) and noncardiac chest pain (NCCP) in 788 (77%). Of patients with ACS, 94 (9.2%) had a myocardial infarction (MI) at presentation (69 non-ST-elevation MI, 25 ST-elevation MI), and 136 had unstable angina. Using a cutpoint of 210 ng/mL to provide 90% specificity, MPO had a sensitivity of 0.18; negative predictive value, 0.69; positive predictive value, 0.47; negative likelihood ratio, 0.91; and a positive likelihood ratio of 1.83 to differentiate ACS and NCCP. Because of the large overlap of quartiles, MPO was not clinically useful to predict serial TnI changes. The C statistics +/- 95% CI for MPO differentiating ACS from NCCP and for AMI versus NCCP were 0.629 +/- 0.04 and 0.666 +/- 0.06, respectively. CONCLUSIONS: Myeloperoxidase has insufficient accuracy for decision making in patients with suspected ACS. PMID- 22093207 TI - Days alive and out of hospital and the patient journey in patients with heart failure: Insights from the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) program. AB - BACKGROUND: Conventional composite outcomes in heart failure (HF) trials, for example, time to cardiovascular death or first HF hospitalization, have recognized limitations. We propose an alternative outcome, days alive and out of hospital (DAOH), which incorporates mortality and all hospitalizations into a single measure. A refinement, the patient journey, also uses functional status (New York Heart Association [NYHA] class) measured during follow-up. The CHARM program is used to illustrate the methodology. METHODS: CHARM randomized 7,599 patients with symptomatic HF to placebo or candesartan, with median follow-up of 38 months. We related DAOH and percent DAOH (ie, percentage of time spent alive and out of hospital) to treatment using linear regression adjusting for follow-up time. RESULTS: Mean increase in DAOH for patients on candesartan versus placebo was 24.1 days (95% CI 9.8-38.3 days, P < .001). The corresponding mean increase in percent DAOH was 2.0% (95% CI 0.8%-3.1%, P < .001). These findings were dominated by reduced mortality (23 days) but enhanced by reduced time in hospital (1 day). Percent time spent in hospital because of HF was reduced by 0.10% (95% CI 0.04%-0.14%, P < .001). The patient journey analysis showed that patients in the candesartan group spent more follow-up time in NYHA classes I and II and less in NYHA class IV. CONCLUSIONS: Days alive and out of hospital, especially percent DAOH, provide a valuable tool for summarizing the overall absolute treatment effect on mortality and morbidity. In future HF trials, percent DAOH can provide a useful alternative perspective on the effects of treatment. PMID- 22093208 TI - Long-term clinical outcome in patients with small vessel disease treated with drug-eluting versus bare-metal stenting. AB - BACKGROUND: DES is superior to BMS in reducing restenosis and repeat revascularization. Available data are less convincing in small vessel disease. Aim of our study is to assess long-term clinical outcome of drug-eluting stents (DES) vs. bare-metal stents (BMS) in small coronary vessel disease. METHODS: Procedural and long-term clinical outcomes were assessed in consecutive patients (pts) treated with stenting of native small coronary arteries (reference vessel diameter and implanted stent < 3mm). RESULTS: Pts enrolled were 645: DES group (n = 277) presented more frequently diabetes (173 [62%] vs. 32 [9%], P < .0001), higher body mass index (27 +/- 5 vs. 26 +/- 4, P = .01) and with previous PCI (115 [42%] vs. 118 [32%], P = .01) as compared to BMS group (n=368). DES group presented more frequently with unstable angina (46 [17%] vs. 38 [10%], P = .02); BMS group presented more frequently with myocardial infarction (103 [28] vs. 43 [15], P = .0002). Reference vessel (2.27 +/- 0.36 vs. 2.24 +/- 0.36, P = .29), minimal lumen (0.81 +/- 0.32 vs. 0.80 +/- 0.31, P = .84) and stent diameter (2.59 +/- 0.17 vs. 2.60 +/- 0.15, P = .69) did not differ between the 2 groups. Lesion length was significantly higher in DES group (15.85 +/- 6.81 vs. 13.66 +/- 7.18, P = .01). At a median clinical follow-up of 3.0 years (IQR range 2.2-4.6), pts with DES showed significantly lower major adverse cardiac events (MACE, HR 0.51, 95%CI 0.33-0.78) and target vessel revascularization (TVR, HR 0.44, 95%CI 0.25 0.78). No differences were observed between the two groups as to death, myocardial infarction and stent thrombosis. CONCLUSIONS: In small vessel disease, DES was more frequently implanted in pts at higher risk of restenosis, though it demonstrated to be more effective than BMS in reducing MACE and TVR at long-term follow-up. PMID- 22093209 TI - Mode of death after contemporary percutaneous coronary intervention: a report from the Evaluation of Drug Eluting Stents and Ischemic Events registry. AB - BACKGROUND: When selecting clinical trial end points, some investigators prefer cardiovascular death (CVD) while others believe that all-cause mortality is more relevant. However, the relative contribution of CVD to 1-year mortality after contemporary percutaneous coronary intervention (PCI) is not known. METHODS: We evaluated the mode of death (MOD) in EVENT, a prospective PCI registry at 55 US hospitals. Vital status was assessed at 6 and 12 months as part of the study protocol, and MOD was independently reviewed in blinded fashion. RESULTS: Between 2004 and 2007, EVENT enrolled 10,144 patients of whom 295 (2.9%) died within the first year: 51 (17%) <=30 days; and 244 (83%) between 31 and 365 days after index PCI. Overall, CVD accounted for 42% of deaths, and no clear cause could be identified in a substantial subgroup (25% of deaths). Among patients who died <=30 days, the MOD was more likely to be CVD (odds ratio 3.96, 95% CI 2.08-7.55), whereas the incidence of CVD and non-CVD was similar after 30 days. Findings were similar after a series of sensitivity analyses including reassignment of unknown MOD to the CVD category, using multiple imputation modeling, or when evaluating MOD in prespecified subgroups of patients with diabetes, acute coronary syndromes, or left ventricular dysfunction. CONCLUSIONS: Among unselected PCI patients, 1-year mortality is approximately 3%, and CVD is confirmed in <50% of all deaths. Regardless of analytic approach, CVD is the primary contributor to overall mortality during the first 30 days after PCI, whereas rates of CVD and non-CVD are remarkably similar after the first month after PCI. PMID- 22093210 TI - Long-term tissue coverage of a biodegradable polylactide polymer-coated biolimus eluting stent: comparative sequential assessment with optical coherence tomography until complete resorption of the polymer. AB - BACKGROUND: Biolimus-eluting stents (BESs) with a biodegradable polymer in abluminal coating achieve more complete coverage at 9 months compared with sirolimus-eluting stents (SESs) with a durable polymer, as assessed by optical coherence tomography (OCT). Whether this advantage persists or augments after complete resorption of the polymer (>12 months) is unknown. METHODS: The LEADERS trial compared the performance of BES with that of SES. Patients were randomly allocated to a sequential angiographic follow-up, including OCT in selected sites, at 9 and 24 months. Struts coverage was compared using Bayesian hierarchical models as the primary outcome for the OCT substudy. RESULTS: Fifty six patients (26 BES, 30 SES) were enrolled in the OCT substudy. Twenty-one patients (10 BES, 11 SES) agreed to perform a second OCT follow-up at 24 months. Eleven lesions and 12 stents were analyzed sequentially in the BES group (2,455 struts at 9 months, 2,131 struts at 24 months) and 11 lesions and 18 stents in the SES group (3,421 struts at 9 months, 4,170 struts at 24 months). The previously reported advantage of BES over SES in terms of better strut coverage at 9 months was followed by improvement in coverage of the SES, resulting in identical coverage in both BES and SES at 24 months: 1.5% versus 1.8% uncovered struts, difference -0.2%, 95% credibility interval, -3.2% to 2.6%, P = .84. CONCLUSIONS: More complete strut coverage of BES as compared with SES at 9 months was followed by improvement of coverage in SES between 9 and 24 months and a similar long-term coverage in both stent types at 24 months. PMID- 22093211 TI - Trends in the use of diagnostic coronary angiography, percutaneous coronary intervention, and coronary artery bypass graft surgery across North Carolina. AB - BACKGROUND: Although variation in use of invasive coronary procedures has been shown, the relationship between invasive diagnostic cardiac catheterization (Cath) and subsequent revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is not known. We evaluated the temporal trends and variation in invasive Cath, PCI, and CABG across hospital systems in North Carolina. METHODS: All Cath, PCI, and CABG procedures performed in North Carolina from 2003 to 2009 were identified using data reported in the annual North Carolina State Medical Facilities Plan. Rates and variation in procedure use, relative rates of PCI to Cath, CABG to Cath, and CABG to PCI were compared over the study period between hospitals that performed at least 25 Cath, 25 PCI, and 25 CABG procedures. RESULTS: The rates of all invasive procedures per 100,000 population declined: 24% for Cath, 16% for PCI, and 35% for CABG. However, the relative rate of PCI to Cath over the study period increased by 11%, whereas the relative rate of CABG to Cath decreased by 13%. Hospital level analysis showed significant variation in the relative rate of both PCI to Cath (10%-90%, P < .05) and CABG to Cath (5%-35%, P < .05). CONCLUSIONS: Although the use of all invasive cardiac procedures declined, the relative rate of PCI to Cath increased over the study period. There was also significant variation in the mode of revascularization (CABG and PCI) across hospital systems in North Carolina. Further research is needed to understand drivers of coronary revascularization. PMID- 22093201 TI - Management of acute coronary syndromes in developing countries: acute coronary events-a multinational survey of current management strategies. AB - BACKGROUND: The burden of cardiovascular diseases is predicted to escalate in developing countries. We investigated the descriptive epidemiology, practice patterns, and outcomes of patients hospitalized with acute coronary syndromes (ACS) in African, Latin American, and Middle Eastern countries. METHODS: In this prospective observational registry, 12,068 adults hospitalized with a diagnosis of ACS were enrolled between January 2007 and January 2008 at 134 sites in 19 countries in Africa, Latin America, and the Middle East. Data on patient characteristics, treatment, and outcomes were collected. RESULTS: A total of 11,731 patients with confirmed ACS were enrolled (46% with ST-elevation myocardial infarction [STEMI], 54% with non-ST elevation-ACS). During hospitalization, most patients received aspirin (93%) and a lipid-lowering medication (94%), 78% received a beta-blocker, and 68% received an angiotensin converting enzyme inhibitor. Among patients with STEMI, 39% did not receive fibrinolysis or undergo percutaneous coronary intervention. All-cause death at 12 months was 7.3% and was higher in patients with STEMI versus non-ST elevation-ACS (8.4% vs 6.3%, P < .0001). Clinical factors associated with higher risk of death at 12 months included cardiac arrest, antithrombin treatment, cardiogenic shock, and age >70 years. CONCLUSIONS: In this observational study of patients with ACS, the use of evidence-based pharmacologic therapies for ACS was quite high, yet 39% of eligible patients with STEMI received no reperfusion therapy. These findings suggest opportunities to further reduce the risk of long-term ischemic events in patients with ACS in developing countries. PMID- 22093212 TI - Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: evidence from a 37,229 patient meta-analysis. AB - BACKGROUND: More intensive glycemic control reduces the risk of microvascular disease in patients with diabetes mellitus but has not been proven to reduce the risk of macrovascular events such as myocardial infarction and stroke. Poorer glycemic control, as indicated by glycated hemoglobin level concentration, is associated with an increased risk of heart failure (HF), but it is not known whether improved glycemic control reduces this risk. We conducted a meta-analysis of randomized controlled trials comparing strategies of more versus less intensive glucose-lowering that reported HF events. METHODS: Two investigators independently searched PubMed, the Cochrane CENTRAL register of controlled trials, metaRegister, pre-MEDLINE, and CINAHL from January 1970 to October 2010 for prospective controlled randomized trials comparing a more intensive glucose lowering regimen to a standard regimen. The outcome of interest was HF-related events (both fatal and nonfatal). Odds ratios (ORs) were calculated from published data from relevant trials and pooled with a random-effects meta analysis. RESULTS: A total of 37,229 patients from 8 randomized trials were included in the analysis. Follow-up ranged from 2.3 to 10.1 years, and the overall number of HF-related events was 1469 (55% in the intensive treatment arm). The mean difference in glycated hemoglobin level between patients given standard treatment and those allocated to a more intensive regimen was 0.9%. Overall, the risk of HF-related events did not differ significantly between intensive glycemic control and standard treatment (OR 1.20, 95% CI 0.96-1.48), but the effect estimate was highly heterogeneous (I(2) = 69%). At subgroup analysis, intensive glycemic control achieved with high thiazolidinediones use significantly increased HF risk (OR 1.33, 95% CI 1.02-1.72). CONCLUSIONS: More intensive glycemic control in patients with type 2 diabetes mellitus did not reduce the occurrence of HF events. Furthermore, intensive glycemic control with thiazolidinediones increased the risk of HF. These findings question a direct mechanistic link between hyperglycemia and HF. PMID- 22093213 TI - Effect of controlled reduction of body iron stores on clinical outcomes in peripheral arterial disease. AB - BACKGROUND: Published results from a controlled clinical trial in patients with peripheral arterial disease found improved outcomes with iron (ferritin) reduction among middle-aged subjects but not the entire cohort. The mechanism of the age-specific effect was explored. METHODS: Randomization to iron reduction (phlebotomy, n = 636) or control (n = 641) stratified by prognostic variables permitted analysis of effects of age and ferritin on primary (all-cause mortality) and secondary (death, nonfatal myocardial infarction, and stroke) outcomes. RESULTS: Iron reduction improved outcomes in youngest age quartile patients (primary outcome hazard ratio [HR] 0.44, 95% CI 0.21-0.92, P = .028; secondary outcome HR 0.34, 95% CI 0.19-0.61, P < .001). Mean follow-up ferritin levels (MFFL) declined with increasing entry age in controls. Older age (P = .035) and higher ferritin (P < .001) at entry predicted poorer compliance with phlebotomy and rising MFFL in iron-reduction patients. Intervention produced greater ferritin reduction in younger patients. Improved outcomes with lower MFFL were found in iron-reduction patients (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .028; secondary outcome HR 1.10, 95% CI 1.0-1.20, P = .044) and the entire cohort (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .037). Improved outcomes occurred with MFFL below versus above the median of the entire cohort means (primary outcome HR 1.48, 95% CI 1.14-1.92, P = .003; secondary outcome HR 1.22, 95% CI 0.99-1.50, P = .067). CONCLUSIONS: Lower iron burden predicted improved outcomes overall and was enhanced by phlebotomy. Controlling iron burden may improve survival and prevent or delay nonfatal myocardial infarction and stroke. PMID- 22093214 TI - Delayed arterial healing 5 years after implantation of sirolimus-eluting stents: no smoke without fire. PMID- 22093216 TI - Liposomes and other vesicular systems: structural characteristics, methods of preparation, and use in nanomedicine. AB - Vesicular systems, especially liposomes, have generated a great deal of interest as intelligent materials for the delivery of bioactive molecules since they can be used as sensitive containers that respond to external stimuli, such as pressure, pH, temperature, or concentration changes in the medium, triggering modifications in their supramolecular structure. The control of the nanostructure particle size and size distribution, membrane morphology, and supramolecular organization-of these self-assembled systems is of profound importance for their application in drug delivery and the discovery of new nanomedicines. This chapter will describe the chemical structure of vesicles and their pharmacological properties, conventional and new vesicle preparation methods and structural characterization, as well as their use in the rational design and fabrication of nanomedicines. PMID- 22093215 TI - Pneumocystis jirovecii pneumonia is rare in renal transplant recipients receiving only one month of prophylaxis. AB - Prophylaxis against Pneumocystis jirovecii pneumonia (PCP) is recommended for at least 4-12 months after solid organ transplant. In our center, renal transplant recipients receive only 1 month of post-transplant trimethoprim-sulfamethoxazole, which also may provide limited protection against Nocardia. We identified only 4 PCP cases and 4 Nocardia cases in 1352 patients receiving renal and renal pancreas transplant from 2003 to 2009 at the University of Michigan Health System. Two PCP cases were identified <1 year after transplant, and 2 PCP cases were identified >1 year after transplant (gross attack rate 4/1352, 0.3%). Two Nocardia cases were identified <1 year after transplant, and 2 cases were identified >1 year after transplant. All identified cases received induction therapy (7 of 8 with anti-thymocyte globulin), whereas about one-half of all renal transplant patients received induction therapy at our institution. No patient was treated for rejection within 6 months of PCP; 2 of 4 patients with PCP had recent cytomegalovirus infection. All patients with PCP and 3 of 4 patients with Nocardia survived. The benefits of prolonged PCP prophylaxis should be weighed against the adverse events associated with prolonged use of antimicrobials. PMID- 22093217 TI - Luminescent quantum dots, making invisibles visible in bioimaging. AB - Semiconductor quantum dots (QDs), their size-dependent tunable absorption and emission in the visible and near-infrared regions, narrow emission and broad absorption bands, large one- and multiphoton absorption cross sections, brightness, and photostability make them powerful light sources in the nanoscale region that will help to advance biotechnologies. This chapter overviews the present status and prospects of QDs by focusing on bioconjugation of QDs, and applications of bioconjugated QDs to surface-cell as well as inside-cell labeling for imaging and photodynamic therapy (PDT). In particular, it highlights the synthesis of biocompatible QDs, surface modification of QDs, conjugation of QDs with a variety of ligands and antibodies, potential targets of bioconjugated QDs in cells, nonspecific and specific surface-cell labeling, nonspecific and specific delivery of QDs in cells, and PDT based on QDs. Such information will be helpful for both applications of QDs for bioimaging and extension of QD technologies to other nanoparticles. PMID- 22093218 TI - Fabrication of dendrimers toward biological application. AB - Dendrimers consisting of inner core and peripheral shell are well-designed branching architectures with abundant terminal groups. Therefore, the high level of control over dendritic architectures makes dendrimers ideal carriers in biomedical application. In addition, the toxicity of dendrimers mainly comes from the high cationic charge density in the periphery, where charges interact with biological cell membrane and then result in membrane disruption. Two strategies have been utilized to minimize the toxicity of dendrimers: first, selecting neutral or anionic biocompatible dendrimers, and second, masking of peripheral charge by chemical modification. Then the focus of this chapter shifts to biomedical application of biocompatible dendrimers, including drug delivery systems of dendrimers, targeting delivery by dendrimers, and applications of dendrimers for therapy and as imaging agents for inspection. PMID- 22093219 TI - Carbohydrate-based nanoparticles for potential applications in medicine. AB - Although carbohydrates are essential for life, the development of medical tools based on these important biomolecules is significantly slower than those based on proteins or nucleic acids. This chapter deals with the applications of nanoparticles decorated with carbohydrates and discusses the perspectives of their use in the field of medicine. The review is divided into two sections: diagnosis and therapy. Within these topics, the focus will be on two main types of systems: carbohydrate-coated metallic nanoparticles in which the carbohydrate ligands are "covalently" linked to a nanosized metallic cluster and polysaccharide-encapsulated metallic cores. The former glyconanoparticles (GNPs) represent a powerful chemical tool in the field of glycobiology as a specific carbohydrate can be selected to exert a concrete biological function and profile carbohydrate-based interactions. Up to now, these GNPs have been mainly used as potential anti-adhesion agents against pathogens. The opportunity of inserting multifunctionality and changing the nucleus size/material is giving birth to new targeted systems for imaging and therapy. On the other hand, nonmetallic polysaccharide-based nanoparticles have been successfully used as drug delivery carriers in addition to molecular imaging. PMID- 22093220 TI - Carbon nanotubes: engineering biomedical applications. AB - Carbon nanotubes (CNTs) are cylinder-shaped allotropic forms of carbon, most widely produced under chemical vapor deposition. They possess astounding chemical, electronic, mechanical, and optical properties. Being among the most promising materials in nanotechnology, they are also likely to revolutionize medicine. Among other biomedical applications, after proper functionalization carbon nanotubes can be transformed into sophisticated biosensing and biocompatible drug-delivery systems, for specific targeting and elimination of tumor cells. This chapter provides an introduction to the chemical and electronic structure and properties of single-walled carbon nanotubes, followed by a description of the main synthesis and post-synthesis methods. These sections allow the reader to become familiar with the specific characteristics of these materials and the manner in which these properties may be dependent on the specific synthesis and post-synthesis processes. The chapter ends with a review of the current biomedical applications of carbon nanotubes, highlighting successes and challenges. PMID- 22093222 TI - Polymer nanoparticles. AB - Over the past few decades, interest in designing and developing polymeric nanoparticles has undergone considerable explosion. Indeed, these nanoparticulated polymer-based systems provide potential solution to improve therapeutic efficacy and diagnosis sensitivity. In this chapter, general properties, production, and characterization of polymer nanoparticles are introduced. Specifically, the development and application of polyhydroxyalkanoate (PHA)-based nanoparticles are emphasized because of the good biocompatible, biodegradable properties, as well as their mechanical flexibility. These PHAs nanoparticles can serve as targeting drug delivery carriers and protein purification and immobilization matrices. The perspective outlook in the last section highlights the future application of polymer nanoparticles in translational science. PMID- 22093221 TI - Engineered biological entities for drug delivery and gene therapy protein nanoparticles. AB - The development of genetic engineering techniques has speeded up the growth of the biotechnological industry, resulting in a significant increase in the number of recombinant protein products on the market. The deep knowledge of protein function, structure, biological interactions, and the possibility to design new polypeptides with desired biological activities have been the main factors involved in the increase of intensive research and preclinical and clinical approaches. Consequently, new biological entities with added value for innovative medicines such as increased stability, improved targeting, and reduced toxicity, among others have been obtained. Proteins are complex nanoparticles with sizes ranging from a few nanometers to a few hundred nanometers when complex supramolecular interactions occur, as for example, in viral capsids. However, even though protein production is a delicate process that imposes the use of sophisticated analytical methods and negative secondary effects have been detected in some cases as immune and inflammatory reactions, the great potential of biodegradable and tunable protein nanoparticles indicates that protein-based biotechnological products are expected to increase in the years to come. PMID- 22093223 TI - Nanobiotechnology and personalized medicine. AB - This chapter will start with a definition and scope of personalized medicine and describe how various nanobiotechnologies will contribute to its development. Nanodiagnostics and its combination with therapeutics as well as nanoparticle based drug delivery will play an important role. The most important applications of nanobiotechnology will be personalized management of cancer, neurological disorders, and cardiovascular diseases. PMID- 22093224 TI - Tissue engineering using magnetite nanoparticles. AB - The major advantage of magnetic manipulation is "remote control." Magnetic labeling of cells with magnetic nanoparticles enables the manipulation of cells and also the control of cell functions by applying an external magnetic field. "Functional" magnetite nanoparticles were developed for cell manipulation using magnetic force, and the magnetite nanoparticles were applied to tissue engineering processes, which are designated as magnetic force-based tissue engineering (Mag-TE). This chapter reviews recent progress in Mag-TE techniques, and the principles and utilities of the applications are discussed. This review covers three topics of magnetic cell manipulation using magnetite nanoparticles, including a magnetic force-based gene transfer technique (magnetofection), magnetic cell patterning using functional magnetite nanoparticles and micro patterned magnetic field gradient concentrators, and finally applications for fabrication of tissue-like constructs in skin, liver, and muscle tissue engineering. PMID- 22093225 TI - Peptide nanoparticles for oligonucleotide delivery. AB - In the past two decades, different methods have emerged for intervention with gene expression, which can be generally referred to as gene therapy. Oligonucleotides (ONs) and their analogs form the basis of the molecules that can be used to modulate gene expression. Unfortunately, due to their physicochemical properties, these molecules require assistance in their intracellular delivery. Cell-penetrating peptides (CPPs) are one class of nonviral delivery vectors that, because of their remarkable translocation properties, have been intensely utilized for the delivery of ON-based molecules, both in vitro and in vivo. This chapter concentrates on the applications of CPPs that directly form nanoparticles with different ONs and facilitate their intracellular delivery. PMID- 22093226 TI - Nanoparticles in molecular diagnostics. AB - The aim of this chapter is to provide an overview of the available and emerging molecular diagnostic methods that take advantage of the unique nanoscale properties of nanoparticles (NPs) to increase the sensitivity, detection capabilities, ease of operation, and portability of the biodetection assemblies. The focus will be on noble metal NPs, especially gold NPs, fluorescent NPs, especially quantum dots, and magnetic NPs, the three main players in the development of probes for biological sensing. The chapter is divided into four sections: a first section covering the unique physicochemical properties of NPs of relevance for their utilization in molecular diagnostics; the second section dedicated to applications of NPs in molecular diagnostics by nucleic acid detection; and the third section with major applications of NPs in the area of immunoassays. Finally, a concluding section highlights the most promising advances in the area and presents future perspectives. PMID- 22093227 TI - Nanoparticles in cancer chemotherapy. AB - Nanotechnology has evolved as an exciting platform in the field of anticancer research with promises to improve the pharmacology of current cancer therapeutics. Nanoparticles confer several advantages over that of free drugs, including their capability to carry high payloads of drugs, with prolonged half life and reduced toxicity of the drugs, and increased targeting efficiency. The wide variety of nanovectors, coupled with the different methods available to conjugate or encapsulate therapeutic and/or imaging agents within, provide us with opportunities to fine-tune the pharmacological properties of these agents and open up new vistas in anticancer research. Here, we will discuss the physicochemical properties of different nanoparticles, their impact on tumor targeting, and their current status in the clinics with respect to cancer chemotherapy. PMID- 22093228 TI - Nanoparticles in gene therapy principles, prospects, and challenges. AB - With the development of genomic technologies, the prospect for gene therapy has progressed rapidly. The major challenge of gene delivery is to improve the transfection efficiencies of the nonviral carriers. Among various nonviral gene vectors, nanoparticles (NPs) offer an ideal platform for the incorporation of all the desirable characteristics into a single gene delivery system. In this chapter, some of the most popularly used lipid- and polymer-based gene delivery vectors and their components are discussed in terms of their characteristics, advantages, and limitations. Although substantial progress has been made, further development of sophisticated delivery systems is foreseen for the nonviral vectors' application in gene therapy. Therefore, we have described several effective strategies to enhance the transfection efficiency of nonviral gene vectors. It is hoped that this review will provide an impetus to the expansion of this promising field of nanomedicine. PMID- 22093230 TI - The design, fabrication, and application of nano-objects. PMID- 22093231 TI - Late presentation of HIV infection among adults in New Zealand: 2005-2010. AB - BACKGROUND: Early diagnosis of HIV infection is important for the individual and for disease control. A consensus was recently reached among European countries on definitions of timing of presentation for care: 'Late presentation' refers to entering care with a CD4 count <350 cells/MUL or an AIDS-defining event, regardless of the CD4 count. Presentation with 'advanced HIV disease' is a subset having a CD4 count <200 cells/MUL and also includes all who have an AIDS-defining event regardless of CD4 count. This study examines timing of presentation in New Zealand from 2005 to 2010. METHODS: Since 2005, information on the initial CD4 cell count has been requested on all people newly diagnosed with HIV infection through antibody testing in New Zealand. Excluded in this analysis were those previously diagnosed overseas or for an immigration medical. RESULTS: A CD4 cell count was provided for 606 (80.3%) of the 755 newly diagnosed adults. Overall, 50.0% were 'late presenters' and 32.0% had 'advanced HIV disease'. Compared with men who have sex with men (MSM), people heterosexually infected were more likely to present late. 'Late presentation' and presentation with 'advanced HIV disease' were significantly more common among older MSM. Maori and Pacific MSM were more likely to present with 'advanced HIV disease'. Compared with European MSM, the age-adjusted relative risks for Maori and Pacific MSM were 2.1 [95% confidence interval (CI) 1.4-3.2] and 2.5 (95% CI 1.2-5.0), respectively. CONCLUSIONS: The high proportion of people presenting late reflects inadequate levels of HIV testing. The lower proportion of late presentations among MSM compared with those heterosexually infected may be explained by a higher proportion of recent locally acquired infections together with different testing patterns. PMID- 22093232 TI - Ocular fundus pathology and chronic kidney disease in a Chinese population. AB - BACKGROUND: Previous study indicated a high prevalence of ocular fundus pathology among patients with chronic kidney disease (CKD), while the relationship between them has never been explored in a Chinese Population. METHODS: This cross sectional study included 9 670 participants enrolled in a medical screening program. Ocular fundus examination was performed by ophthalmologists using ophthalmoscopes. The presence of eGFR less than 60 mL/min/1.73 m(2) and/or proteinuria was defined as CKD. RESULTS: Compared to participants without CKD, participants with CKD had higher prevalence of retinopathy (28.5% vs. 16.3%, P < 0.001), glaucoma suspect (3.1% vs. 1.8%, P = 0.004), age-related macular degeneration (1.7% vs. 0.9%, P = 0.01) and overall eye pathology (32.0% vs. 19.4%, P < 0.001). After adjusting for potential confounders, the odds ratio of proteinuria for overall eye pathology and retinopathy was 1.29 (95% confidence interval [CI] 1.07-1.55) and 1.37 (95% CI 1.12-1.67), respectively. The results were robust after excluding participants with hypertension or with diabetes. CONCLUSIONS: Ocular fundus pathology is common among Chinese patients with CKD. Regular eye exam among persons with proteinuria is warranted. PMID- 22093233 TI - A randomized, single-blind, postmarketing study of multiple energy levels of high intensity focused ultrasound for noninvasive body sculpting. AB - BACKGROUND: High-intensity focused ultrasound (HIFU) is a nonsurgical, noninvasive body sculpting method. OBJECTIVE: To investigate preferences for treatment settings using a HIFU device. MATERIALS AND METHODS: HIFU was applied to the anterior abdomen in three passes of decreasing depth (1.6, 1.3, and 1.1 cm) in patients randomized to HIFU energy levels (each of 3 passes [total]) of 47 (141), 52 (156), or 59 (177) J/cm(2). The primary assessment was week 12 post treatment change from baseline waist circumference at the level of the iliac crest for all treatment groups combined. RESULTS: The primary assessment achieved statistical significance (least squares mean 2.51 cm, 95% confidence interval [CI] = -3.14 to -1.88; p < .001), with no significant differences between groups. At week 12, 69% to 86% of patients and 73% to 79% of investigators rated appearance as improved or much improved. The average worst pain (100-mm visual analog scale) experienced during treatment was mild (47 J/cm(2): 17.1 mm, 95% CI = 4.33-29.81 mm; 52 J/cm(2): 24.6 mm, 95% CI = 12.24-36.95 mm; 59 J/cm(2): 30.9 mm, 95% CI = 18.71-43.17 mm). There were no serious adverse events. CONCLUSION: HIFU treatment at different energy levels and multiple tissue depths was well tolerated and effective in reducing waist circumference. PMID- 22093229 TI - Cell delivery of therapeutic nanoparticles. AB - Nanomedicine seeks to manufacture drugs and other biologically relevant molecules that are packaged into nanoscale systems for improved delivery. This includes known drugs, proteins, enzymes, and antibodies that have limited clinical efficacy based on delivery, circulating half-lives, or toxicity profiles. The <100 nm nanoscale physical properties afford them a unique biologic potential for biomedical applications. Hence they are attractive systems for treatment of cancer, heart and lung, blood, inflammatory, and infectious diseases. Proposed clinical applications include tissue regeneration, cochlear and retinal implants, cartilage and joint repair, skin regeneration, antimicrobial therapy, correction of metabolic disorders, and targeted drug delivery to diseased sites including the central nervous system. The potential for cell and immune side effects has necessitated new methods for determining formulation toxicities. To realize the potential of nanomedicine from the bench to the patient bedside, our laboratories have embarked on developing cell-based carriage of drug nanoparticles to improve clinical outcomes in infectious and degenerative diseases. The past half decade has seen the development and use of cells of mononuclear phagocyte lineage, including dendritic cells, monocytes, and macrophages, as Trojan horses for carriage of anti-inflammatory and anti-infective medicines. The promise of this new technology and the perils in translating it for clinical use are developed and discussed in this chapter. PMID- 22093234 TI - Ester-linked hen egg white lysozyme shows a compact fold in a molecular dynamics simulation - possible causes and sensitivity of experimentally observable quantities to structural changes maintaining this compact fold. AB - Prediction and understanding of the folding and stability of the 3D structure of proteins is still a challenge. The different atomic interactions, such as non polar contacts and hydrogen bonding, are known but their exact relative weights and roles when contributing to protein folding and stability are not identified. Initiated by a previous molecular dynamics simulation of fully ester-linked hen egg white lysozyme (HEWL), which showed a more compact fold of the ester-linked molecule compared to the native one, three variants of this protein are analyzed in the present study. These are 129-residue native HEWL, partly ester-linked HEWL, in which only 34 peptide linkages that are not involved in the helical or beta-strand parts of native HEWL were replaced by ester linkages, and fully (126 residues) ester-linked HEWL. Native and partly ester-linked HEWL showed comparable behaviour, whereas fully ester-linked HEWL could not maintain the native secondary structure of HEWL in the simulation and adopted a more compact fold. The conformational changes were analyzed by comparing simulation averaged values of quantities that can be measured by NMR, such as (1)H-(15)N backbone order parameters, residual dipolar couplings, proton-proton NOE distances and (3)J-couplings with the corresponding values derived from experimental NMR data for native HEWL. The information content of the latter appeared to be insufficient to detect the local conformational rearrangements upon esterification of the loop regions of the protein. For fully ester-linked HEWL, a significantly reduced agreement was observed. Upon esterification, the backbone side chain and side chain-side chain hydrogen-bonding pattern of HEWL changes to maintain its compactness and thus the structural stability of the ester-linked lysozymes. PMID- 22093235 TI - Management of pilomatrix carcinoma: a case report of successful treatment with Mohs micrographic surgery and review of the literature. PMID- 22093236 TI - Attitudes towards different containment measures: a questionnaire survey in Finnish adolescent psychiatry. AB - Use of containment measures in the treatment of underage patients is controversial, and empirical evidence about which containment methods are preferred is lacking. This study aimed to investigate attitudes of staff towards various containment measures in the field of adolescent psychiatry. The sample comprised 128 Finnish nurses and doctors working in closed wards with 13- to 17 year-old patients. The attitudes were studied using the Attitude to Containment Measures Questionnaire. The three methods with the most approval were as-needed medication, transfer to specialist locked wards and mechanical restraint. The method with the least approval was the net bed. Total approval scores for the various containment measures were very similar among nurses and doctors. The differences appeared in attitudes towards mechanical restraint and constant observation, doctors showing a more critical attitude. Women tended to be more critical than men, but only intramuscular medication and mechanical restraint reached statistical significance. The results emphasize the importance of wide ranging and in-depth training as well as the difficulty of changing practices in psychiatric wards while attitudes are so strongly pro-containment. PMID- 22093237 TI - Relationships between motor aspects of gait impairments and activity limitations in people with Parkinson's disease: a systematic review. AB - Gait disorders are common in people with Parkinson's disease (PD) yet their associations with activity limitations remain poorly understood. The objective of this review is to investigate the relationships between gait impairments and activity limitations in people with idiopathic PD. Six electronic databases (MEDLINE ISI, CINAHL, Web of Science ISI, EMBASE, PsycINFO and Scopus) were systematically searched using relevant terms to source for English-language studies published between 1900 and January 2011. Only studies that reported associations between impairments and activity limitations were considered for the review. The methodological quality of eligible studies was evaluated using a customized checklist by two independent reviewers. Data on participant characteristics, disease severity and associations between variables were extracted using a standardized data extraction form. Correlation coefficients were transformed to standardized scores and pooled using the fixed or random effects models. 16 of the 1735 studies screened were included, comprising 1882 participants. Large effect sizes were found between postural instability measured by the Berg Balance scale and activity limitation measured by the Unified Parkinson's Disease Rating Scale Activities of Daily Living (UPDRS ADL) section ( 0.81; 95% CI, -0.99 to -0.63; p < 0.001). Gait hypokinesia measured by gait speed was significantly correlated with UPDRS ADL (-0.41; 95% CI, -0.56 to -0.26; p < 0.001). Gait freezing measured by the Freezing of Gait Questionnaire was associated with reduction in ADL (0.45; 95% CI, 0.36 to 0.54; p < 0.001). Knowledge of gait disturbances and their associations with disability may help to guide clinicians in assessing patients to optimize functional outcomes. PMID- 22093238 TI - Clinical and radiological features of respiratory syncytial virus in solid organ transplant recipients: a single-center experience. AB - BACKGROUND: Respiratory syncytial virus (RSV) infections range from upper respiratory illness to severe lower respiratory disease. There is no universally accepted treatment for RSV in solid organ transplant (SOT) recipients. METHODS: Retrospective review of adult SOT patients with RSV infections, between January 2007 and December 2009, in a single transplant center was performed. RESULTS: During the 3-year period, a total of 24 adults developed RSV infection, including 12 (50%) SOT recipients (5 kidneys, 4 livers, and 3 lungs). Most cases were seen in 2009 during the influenza H1N1 pandemic, likely as a result of increased testing. In 83% of the cases, the diagnosis was based on RSV antigen detection, which was also used to follow subsequent shedding (mean duration: 20.6 days). Most of the cases presented with lower respiratory disease and required hospitalization. All the patients were on at least two classes of immunosuppressive drugs. We observed a lower lymphocyte count in patients with lower respiratory tract infection. Computed tomography was superior to chest x ray in demonstrating pulmonary disease, with the most common findings being pulmonary nodules and ground-glass opacities. Novel radiographic findings were small cavities and pleural effusions. No co-infections were documented, and no mortality could be attributed to RSV. Inhaled or oral ribavirin was administered in 67% of the cases, with variations in the treatment regimens. CONCLUSION: SOT recipients accounted for half of all adult cases of RSV at our institution. Type and length of treatment varied widely, and we cannot conclude that outcomes differed between treatments with oral or inhaled ribavirin. Current therapeutic management of RSV in SOT is empiric, and can be rather expensive and difficult, without clear evidence of effectiveness. PMID- 22093240 TI - Multiple signal pathways in obesity-associated cancer. AB - Obesity is increasing worldwide and reaches to a large proportion of the population in developed countries. Thus, obesity-associated cancer has become a major health problem. Multiple cancer risk factors in obesity have been identified including insulin/insulin-like growth factor axis, adipokines and cytokines; and multiple intracellular signal pathways have been studied. However, the role of each signal pathway in obesity-associated cancer is controversial. In this review, the recent studies on signal pathways in obesity-associated cancer are summarized and a unified explanation is provided. Multiple risk factors could initially activate phosphoinositide 3-kinase (PI3K/Akt), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) pathways. With increased severity of obesity, mammalian target of rapamycin (mTOR), which is down-stream of both PI3K/Akt and MAPK, is highly activated. Activated mTOR in turn inhibits the PI3K/Akt pathway and further activates the STAT3 pathway. This may explain the activation of the PI3K/Akt pathway at the early stage of obesity and its inhibition at the later stage. mTOR inhibition may be used for cancer therapy, but it may be necessary to be combined with the PI3K/Akt inhibitor as decreased mTOR activity will release its feedback inhibition on the PI3K/Akt pathway, which is under the influence of multiple cancer risk factors in obesity. Thus, dual inhibitors of PI3K and mTOR may provide a novel approach. PMID- 22093239 TI - Studies of the transmissibility of the agent of bovine spongiform encephalopathy to the domestic chicken. AB - BACKGROUND: Transmission of the prion disease bovine spongiform encephalopathy (BSE) occurred accidentally to cattle and several other mammalian species via feed supplemented with meat and bone meal contaminated with infected bovine tissue. Prior to United Kingdom controls in 1996 on the feeding of mammalian meat and bone meal to farmed animals, the domestic chicken was potentially exposed to feed contaminated with the causal agent of BSE. Although confirmed prion diseases are unrecorded in avian species a study was undertaken to transmit BSE to the domestic chicken by parenteral and oral inoculations. Transmissibility was assessed by clinical monitoring, histopathological examinations, detection of a putative disease form of an avian prion protein (PrP) in recipient tissues and by mouse bioassay of tissues. Occurrence of a progressive neurological syndrome in the primary transmission study was investigated by sub-passage experiments. RESULTS: No clinical, pathological or bioassay evidence of transmission of BSE to the chicken was obtained in the primary or sub-passage experiments. Survival data showed no significant differences between control and treatment groups. Neurological signs observed, not previously described in the domestic chicken, were not associated with significant pathology. The diagnostic techniques applied failed to detect a disease associated form of PrP. CONCLUSION: Important from a risk assessment perspective, the present study has established that the domestic chicken does not develop a prion disease after large parenteral exposures to the BSE agent or after oral exposures equivalent to previous exposures via commercial diets. Future investigations into the potential susceptibility of avian species to mammalian prion diseases require species-specific immunochemical techniques and more refined experimental models. PMID- 22093241 TI - Comparison of gene expression of tissue inhibitor of matrix metalloproteinase-1 between continuous and intermittent distraction osteogenesis: a quantitative study on rabbits. AB - BACKGROUND: Distraction osteogenesis is a controlled surgical procedure that initiates a regenerative process and uses mechanical strain to enhance the biological responses of the injured tissues to create new bone. To explore the effect of high-frequency mechanical traction on the expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), we compared the gene expression of TIMP-1 between continuous and intermittent distraction osteogenesis using a rabbit model of mandibular lengthening. MATERIALS AND METHODS: Forty adult New Zealand white rabbits were randomly assigned to the intermittent and continuous distraction groups. A unilateral mandibular osteotomy was performed and a custom designed manual-driven or auto-driven distractor was bridged over the osteotomy segments. Animals were sacrificed at day-6, day-10, day-14 and day-21 after osteotomy. Samples were examined with real-time polymerase chain reaction (PCR). RESULTS: Real-time PCR examination showed significantly higher mRNA levels of TIMP-1 under continuous distraction than that under intermittent distraction at day-6 and day-10. No significant differences were found at day-14 and day-21. CONCLUSION: High-frequency traction provides a good mechanical environment for accelerating bone formation by up-regulating TIMP-1. PMID- 22093242 TI - Influences of palatoplasty by the push-back procedure on craniofacial morphology and growth. AB - PURPOSE: For patients with a cleft palate, the push-back procedure which accompanies posterior shifting of palatal flap is thought to be most effective way of. achieving adequate velopharyngeal function. In this study, we aimed to evaluate the influences of the push-back procedure on the craniofacial morphology and its growth. MATERIAL AND METHODS: Using cephalometry we compared the craniofacial morphology and growth of three groups of Japanese children, living in the same region (Hokkaido, Japan). 1) 28 children (13 girls and 15 boys) with operated submucous cleft palates at the ages of 9 and 14 respectively. 2) 12 age matched children (7 girls and 5 boys) with unoperated submucous cleft palates. 3) 60 age-matched non-cleft children (30 girls and 30 boys) with normal occlusion. None of them received dentofacial orthopaedic treatment. RESULTS: While the patients who had been operated on had significant differences in posterior upper facial height and inclination of the palatal plane when compared with non-cleft children or unoperated cleft children, they showed no statistically significant difference in anteroposterior positioning of anterior part of the maxilla, compared with the unoperated. CONCLUSIONS: The influences of palatoplasty by the push-back procedure with posterior positioning of the palatal flaps on craniofacial morphology are additional to the cleft palate, and of minor concern. PMID- 22093243 TI - Cranio-maxillofacial non-Hodgkin's lymphoma: clinical and histological presentation. AB - Non-Hodgkin's lymphoma represents about 5% of all malignant lesions of the head and neck. In this study we retrospectively evaluated clinical presentation, histological subtype and long-term prognosis of 42 patients with non-Hodgkin's lymphoma involving the craniofacial area. The mean age at diagnosis was 64 years. More than half of the patients presented with disseminated disease at multiple sites (55%, n=23). In 62% (n=26) the first manifestation was extranodal. The most common affected region was the oral cavity (65%, n=17). Treatment consisted of local therapy, including surgical resection and radiation, as well as chemotherapy with or without local therapy. Recurrence occurred in 31% (n=13) of the treated patients. Mean survival after first diagnosis varied from 17 months in patients presenting with diffuse large B-cell lymphoma (DLBCL), to 8.5 years in patients with follicular lymphoma. The most common histological subtype is DLBCL. Standard treatment for DLBCL consists of chemotherapy combined with CD 20 monoclonal antibody, even after total resection of the tumour. There is high risk of systemic disease in patients presenting with non-Hodgkin's lymphoma and high risk of post therapy recurrence. PMID- 22093244 TI - Ocular and periocular injuries associated with an isolated orbital fracture depending on a blunt cranial trauma: anatomical and surgical aspects. AB - The anatomical location of fractures following blunt cranio-orbital trauma is important for neurosurgeons and maxillofacial surgeons. In this study, 588 cranio orbital fractures following blunt trauma were evaluated retrospectively with regard to the anatomical site and surgical treatment. Orbital cranial nerve injuries and the outcomes of the medical and/or surgical treatment are described. Distribution of the zygomatic complex and orbital fractures were as follows: zygomatic complex fractures (n:304), isolated orbital fractures (n:58), complex comminuted fractures (n:226). In 58 cases, 69 orbit fractures were found (11 bilateral and 47 unilateral fractures). The lateral wall was the most frequent fracture (n:63). The least frequent fracture was the roof of the orbit (n:11). The accompanying lesions were as follows: 89.65% of cases were associated with periorbital haematoma (n:52), 13.79% of cases with retrobulbar haemorrhage (n:8), 96.55% cases with periorbital soft tissue oedema (n:56), 53.45% cases with pneumocephalus (n:31), 8.62% cases with intra-parenchymal contusion (n:5), 6.89% cases with enophthalmia (n:4), 5.17% of cases with rhinorrhoea (n: 3), 5.17% cases with optic bulb injury and adnexial trauma (n:3), 32.76% cases with intra orbital emphysema (n:19), and 20.69% with vision dysfunctions (n:12), of whom 2 had no optic nerve injury. PMID- 22093245 TI - Critical review of the Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA): suggestions for harmonization, implementation and improvement. AB - OBJECTIVE: Clinical laboratories in low- and middle-income countries (LMIC) need fundamental improvement because quality laboratory services are essential for the decision-making capacity of clinicians, health workers and public health authorities. To this end, a tiered accreditation scheme Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA) was developed by WHO-AFRO, CDC and others for clinical laboratories in LMIC. One to five stars are accredited to laboratories based on the level of compliance with a checklist. Our aim was to evaluate the quality and applicability of this accreditation scheme compared with international quality standards. METHODS: We performed a critical review of this scheme to formulate recommendations for implementation, harmonization and improvement. Two analyses were performed: one assessing its coverage of the ISO 15189:2007 standard and one to identify and evaluate priorities of the accreditation checklist. RESULTS: Although the content of the checklist covers all aspects of total quality management, it strongly prioritizes resource management activities. We recommend identifying critical requirements for each tier of accreditation to assure a certain level of quality for each tier or instead using a pass/fail approach towards accreditation. In addition, the checklist should include more questions for assessing proper management, ethics and continuous improvement to meet ISO 15189. CONCLUSION: Launching accreditation schemes for laboratories in LMIC should be encouraged. After further optimization of SLIPTA, clinical laboratories may certainly benefit, leading to more correctly diagnosed patients and less waste of resources. PMID- 22093246 TI - Newly diagnosed psychogenic nonepileptic seizures: health care demand prior to and following diagnosis at a first seizure clinic. AB - Patients with psychogenic nonepileptic seizures (PNES) are heavy users of emergency and nonemergency health care. We performed a 1-year prospective audit of use of a group of PNES-related health care items in patients with newly diagnosed (mean duration: 7.3 months) PNES from PNES onset to diagnosis and from diagnosis to 6 months postdiagnosis. Twenty-eight patients (20 women, age: 34+/ 16 years) were responsible for 14 general practitioner home visits, 31 ambulance calls, 34 emergency department visits, 21 hospital admissions (66 inpatient days), 8 MRI scans, 24 CT scans, 2 standard EEGs, 28 short video EEG recordings, and 5 ambulatory EEG recordings. In the 6 months following diagnosis, there were 2 emergency department visits (94.1% reduction), no hospital admissions (100% reduction), 2 ambulance calls, no general practitioner visits, 1 MRI scan, and no CT scans or EEGs. The immediacy of this marked health care demand reduction suggests that the relationship between presentation of diagnosis and health care demand reduction is causal. PMID- 22093247 TI - What about dads? An exploratory analysis of depressive symptoms in paternal primary caregivers of children with epilepsy. PMID- 22093248 TI - Diagnosis of tuberculosis: the experience at a specialized diagnostic laboratory. AB - This work describes the experience at a tuberculosis clinical laboratory where relatively new TB diagnosis technologies; nucleic acid detection of two target strands, IS6110 and devR, by PCR and microscopic observation drug susceptibility (MODS) were used. The LJ culture was the gold standard. This evaluation was done from August 2007 to July 2009 on 463 sputum samples of tuberculosis suspects at a specialized tuberculosis clinic in Delhi, India.None of the tests we evaluated can accurately detect the presence or absence of Mycobacterium tuberculosis in all the samples and smear microscopy was found to be the most reliable assay in this study.The PCR assay could detect down to 2 pg of H37Rv DNA. Sensitivity, specificity was 0.40, 0.60 and 0.19, 0.81 for smear positive (n = 228) and negative samples (n = 235) respectively. In the MODS assay, sensitivity, specificity of 0.48, 0.52 and 0.38, 0.76 was observed for smear positive and negative samples. Sputum smear microscopy had sensitivity of 0.77 and specificity of 0.70. PMID- 22093249 TI - Human macrophages primed with angiogenic factors show dynamic plasticity, irrespective of extracellular matrix components. AB - Macrophages are important in inflammation as well as in tissue repair processes. They can be activated by various stimuli and classified into two major groups: M1 (classically activated) or M2 (alternatively activated). Inflammation, angiogenesis and matrix remodeling play a major role in tissue repair. Here, we investigate the combined influence of a pro-angiogenic microenvironment and specific extracellular matrix (ECM) components or tissue culture polystyrene (TCPS) on the dynamics of human macrophage polarization. We established that human angiogenically primed macrophages cultured on different ECM components exhibit an M2-like polarization. These M2-like macrophages polarized to M1 and M2 macrophages with classical (LPS and IFNgamma) stimuli and alternative (IL-4 and IL-13) stimuli respectively. Moreover, these M1 and M2 (primary) polarized macrophages rapidly underwent a secondary (re)polarization to M2 and M1 with conditioned media from M2 and M1 primary polarized macrophages respectively. In these initial priming and later (re)polarization processes the soluble factors had a dominant and orchestrating role, while the type of ECM (collagen I, fibronectin, versus tissue culture polystyrene) did not play a crucial role on the polarization of macrophages. PMID- 22093250 TI - Mild cognitive impairment (MCI) twenty years on. PMID- 22093251 TI - Two-year course of cognitive function and mood in adults with congestive heart failure and coronary artery disease: the Heart-Mind Study. AB - BACKGROUND: Congestive heart failure (CHF) has been associated with impaired cognitive function, but it is unclear if these changes are specific to CHF and if they get worse with time. We designed this study to determine if adults with CHF show evidence of cognitive decline compared with adults with and without coronary artery disease (CAD). METHODS: A longitudinal study was carried out of 77 adults with CHF (ejection fraction, EF < 0.4), 73 adults with a clinical history of CAD and EF > 0.6, and 81 controls with no history of CAD. The Cambridge Cognitive Examination of the Elderly (CAMCOG) was the primary outcome measure. Secondary measures included the California Verbal Learning Test (CVLT), digit coding and copying, Hospital Anxiety and Depression Scale (HADS), and the short form health survey (SF36). Endpoints were collected at baseline and after 12 and 24 months. RESULTS: The adjusted CAMCOG scores of CHF participants declined 0.9 points over two years (p = 0.022) compared with controls without CAD. There were no differences between the groups on other cognitive measures. Participants with CHF and with CAD experienced similar changes in cognitive function over two years. Left ventricular EF and six-minute walk test results could not explain the observed associations. CONCLUSIONS: The changes in cognitive function and mood associated with CHF over two years are subtle and not specific to CHF. PMID- 22093252 TI - Delirium in elderly people: a study of a psychiatric liaison service in north India. AB - BACKGROUND: Very few studies from India have studied the phenomenology of delirium. The aim of the present study was to study the phenomenology as measured using the Delirium Rating Scale-Revised-98 (DRS-R98), the associated etiologies and the outcome of delirium among the elderly participants seen by the consultation-liaison psychiatric service in India. In addition, an attempt was made to study the factor structure of symptoms using principal components analysis. METHODS: The case notes of 109 elderly patients referred to psychiatry liaison services were reviewed. RESULTS: The mean age of the sample was 73.35 years (SD: 7.44; range 65-95 years) and two-thirds of the sample had hospital emergent delirium. The mean DRS-R98 severity score was 18.77 and the DRS-R98 total score was 24.81. In 15 patients the DRS-R98 scores were in the subsyndromal range. Among the various symptoms present, most patients had sleep-wake cycle disturbance, disturbance in orientation, attention and short-term memory impairments, fluctuation of symptoms, temporal onset of symptoms and a physical disorder. Principal components analysis identified three factors which explained 43.5% of variance of symptomatology and it yielded a three-factor structure. Endocrine/metabolic disturbances were the commonest associated etiological category with delirium. The mean hospital stay after being referred to psychiatry referral services was 8.89 days, after which delirium improved in 58.7% of cases. The mortality rate during the inpatient stay was 16.5%. CONCLUSIONS: Results suggest that the symptoms of delirium as assessed by DRS-R98 separate out into a three-factor structure. Delirium is commonly associated with metabolic endocrine disturbances and about one-sixth of the patients die during the short inpatient stay. PMID- 22093255 TI - Hypoxia and hypoxia mimetics inhibit TNF-dependent VCAM1 induction in the 5A32 endothelial cell line via a hypoxia inducible factor dependent mechanism. AB - BACKGROUND: We previously reported that iron chelators inhibit TNFalpha-mediated induction of VCAM-1 in human dermal microvascular endothelial cells. We hypothesized that iron chelators mediate inhibition of VCAM-1 via inhibition of iron-dependent enzymes such as those involved with oxygen sensing and that similar inhibition may be observed with agents which simulate hypoxia. OBJECTIVE: We proposed to examine whether non-metal binding hypoxia mimetics inhibit TNFalpha-mediated VCAM-1 induction and define the mechanisms by which they mediate their effects on VCAM-1 expression. METHODS: These studies were undertaken in vitro using immortalized dermal endothelial cells, Western blot analysis, ELISA, immunofluorescence microscopy, quantitative real-time PCR, and chromatin immunoprecipitation. RESULTS: Hypoxia and the non-iron binding hypoxia mimetic dimethyl oxallyl glycine (DMOG) inhibited TNFalpha-mediated induction of VCAM-1. DMOG inhibition of VCAM-1 was dose-dependent, targeted VCAM-1 gene transcription independent of NF-kappaB nuclear translocation, and blocked TNFalpha-mediated chromatin modifications of relevant elements of the VCAM-1 promoter. Combined gene silencing of both HIF-1alpha and HIF-2alpha using siRNA led to a partial rescue of VCAM expression in hypoxia mimetic-treated cells. CONCLUSION: Iron chelators, non-metal binding hypoxia mimetics, and hypoxia all inhibit TNFalpha-mediated VCAM-1 expression. Inhibition is mediated independent of nuclear translocation of NF-kappaB, appears to target TNFalpha-mediated chromatin modifications, and is at least partially dependent upon HIF expression. The absence of complete VCAM-1 expression rescue with HIF silencing implies an important regulatory role for an Fe(II)/alpha-ketoglutarate dioxygenase distinct from the prolyl and asparagyl hydroxylases that control HIF function. Identification of this dioxygenase may provide a valuable target for modulating inflammation in human tissues. PMID- 22093256 TI - Postnatal growth defect in mice upon persistent Hoxa2 expression in the chondrogenic cell lineage. AB - Hoxa2 is a homeotic transcription factor, which is downregulated once chondrogenic differentiation is initiated. We previously generated a transgenic mouse model, which turns Hoxa2 on in cells expressing Collagen II A1, i.e. in cells entering chondrogenesis. As a consequence, mice display a general embryonic delay of ossification and then a postnatal growth defect. Col2a1-Cre mice were crossed with an inducible beta-actin driven Hoxa2 transgene. Spines, vertebrae and limbs were measured and skeletal elements were studied by X-ray, microCT, pQCT, TEM, western-blotting, histomorphometry and immunohistochemistry. Mice expressing Hoxa2 in chondrogenic cells feature a proportionate short stature phenotype with a severe lordosis, which appeared significant from postnatal day 4. Analysis of both cartilage and bone development in affected embryos and mice from birth till P35 did not reveal any major defect in histogenesis, except a reduced number of chondrocytes in the vertebral anlage at E13.5. In conclusion, the sustained expression of Hoxa2 in the chondrocyte lineage is characterized by a proportionate short stature resulting from skeletal growth defect. The indepth analysis of cartilage and bone histogenesis points towards an initial deficit in cell mobilization to enter chondrogenesis. PMID- 22093257 TI - Occurrence of selected estrogens in mangrove sediments. AB - This paper presents results related to the occurrence and distribution of estrogens along the Brazilian coast. Three mangrove areas were chosen to evaluate the presence of estrogens in surface sediments of mangrove forests. The presence of estrogens was observed in all studied sites. 17-alpha-Ethinylestradiol (EE2), a synthetic estrogen, was the most common and has been found in higher concentration (0.45-129.78 ng/g) compared to 17-beta-estradiol (E1) and estrone (E2) (both being natural estrogens). The concentrations of E1 and E2 ranged from 0.02 to 49.27 ng/g and 0.03 to 39.77 ng/g, respectively. Theoretically, under anaerobic conditions EE2 can be reduced to E1 even in environments such as sediments of mangrove forests, which are essentially anaerobic. Even if the concentrations of estrogens seem to be insignificant in some samples, the effects remain uncertain. PMID- 22093258 TI - Time to reflect. PMID- 22093259 TI - International Confederation of Midwives (ICM) 29th Triennial Conference, Durban, South Africa, 19-23 June 2011. PMID- 22093260 TI - First ever Report on the State of the World's Midwifery launched at International Confederation of Midwives 29th Congress in Durban, South Africa, June 19-23, 2011. PMID- 22093261 TI - Phylogenetic, chemical and morphological diversity of cyanobacteria from Portuguese temperate estuaries. AB - Cyanobacteria from estuarine habitats have been poorly studied regarding diversity and potential bioactive compounds production compared with their fresh and marine waters' congeners. In this work, 44 cyanobacteria isolates characterised from three Portuguese estuarine environments. Identification was performed based on diacritical morphological features of the isolates (e.g. cell shape, cell size, presence/absence of sheaths) and on 16S rRNA gene sequences phylogenetic analysis. Diversity of produced secondary metabolites was assessed by molecular and analytical tools. The isolates (mostly benthic forms) belonged to: (i) Chroococcales (Cyanobium, Synechocystis and Synechococcus), (ii) Oscillatoriales (Leptolyngbya, Microcoleus, Phormidium and Romeria) and (iii) Nostocales (Nostoc and Nodularia). 19 morphotypes were assigned at the species level, while phylogeny allowed us to distinguish 21 phylotypes spread amongst three distinct large clades. McyA and sxtI gene fragments were detected in some isolates, despite absence of toxins. Simultaneous presence of anabaenopeptins A and D was for the first time identified in Nostoc (LEGE06077). No correlation between morphological/phylogenetic relationships and the secondary-metabolite profile of the isolates was found. This is the first comprehensive study of estuarine cyanobacteria of Portuguese habitats revealing a diverse array of cyanobacteria that constitute an important source of potential bioactive compounds with ecological relevance and/or biomedical application. PMID- 22093262 TI - Quantitation of human herpesvirus-6 (HHV-6) DNA in a cord blood transplant recipient with chromosomal integration of HHV-6. AB - Chromosomal integration of the human herpesvirus-6 (HHV-6) genome (CIHHV-6) is an important consideration if HHV-6 DNA is detected during the course of transplantation. A 4-year-old girl with refractory anemia with excess blasts type 2 was diagnosed with CIHHV-6 before a cord blood transplantation. HHV-6 DNA was serially quantitated by polymerase chain reaction assay in the transplant period. The possibility of HHV-6 reactivation in a transplant recipient with CIHHV-6 was suspected in our case. PMID- 22093264 TI - Intracoronary transluminal attenuation gradient in coronary CT angiography for determining coronary artery stenosis. AB - Coronary computed tomography angiography (CTA) assessment of calcified or complex coronary lesions is frequently challenging. Transluminal attenuation gradient (TAG), defined as the linear regression coefficient between luminal attenuation and axial distance, has a potential to evaluate the degree of coronary stenosis. We examined the value of TAG in determining the stenosis severity on 64-slice coronary CTA. The value of TAG of 370 major coronary arteries was measured from 7,263 intervals of 5-mm length. Compared with coronary CTA and invasive coronary angiography, TAG decreased consistently and significantly with maximum stenosis severity on a per-vessel basis, from -1.91 +/- 4.25 Hounsfield units/10 mm for diameter stenosis of 0% to 49% to -13.37 +/- 9.81 Hounsfield units/10 mm for diameter stenosis of 100% (p < 0.0001). Adding TAG to the interpretation of coronary CTA improved diagnostic accuracy (p = 0.001), especially in vessels with calcified lesions (N = 127; net reclassification improvement 0.095; p = 0.046). TAG appears to be able to contribute to improved classification of coronary artery stenosis severity in coronary CTA, especially in severely calcified lesions. PMID- 22093263 TI - Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury. AB - Gut-derived endotoxin is a critical factor in the development and progression of alcoholic liver disease (ALD). Probiotics can treat alcohol-induced liver injury associated with gut leakiness and endotoxemia in animal models, as well as in human ALD; however, the mechanism or mechanisms of their beneficial action are not well defined. We hypothesized that alcohol impairs the adaptive response induced hypoxia-inducible factor (HIF) and that probiotic supplementation could attenuate this impairment, restoring barrier function in a mouse model of ALD by increasing HIF-responsive proteins (eg, intestinal trefoil factor) and reversing established ALD. C57BJ/6N mice were fed the Lieber DeCarli diet containing 5% alcohol for 8 weeks. Animals received Lactobacillus rhamnosus GG (LGG) supplementation in the last 2 weeks. LGG supplementation significantly reduced alcohol-induced endotoxemia and hepatic steatosis and improved liver function. LGG restored alcohol-induced reduction of HIF-2alpha and intestinal trefoil factor levels. In vitro studies using the Caco-2 cell culture model showed that the addition of LGG supernatant prevented alcohol-induced epithelial monolayer barrier dysfunction. Furthermore, gene silencing of HIF-1alpha/2alpha abolished the LGG effects, indicating that the protective effect of LGG is HIF-dependent. The present study provides a mechanistic insight for utilization of probiotics for the treatment of ALD, and suggests a critical role for intestinal hypoxia and decreased trefoil factor in the development of ALD. PMID- 22093265 TI - Diagnostic optimization of coronary CT angiography. PMID- 22093266 TI - Flow acceleration time and ratio of acceleration time to ejection time for prosthetic aortic valve function. AB - OBJECTIVES: We sought to evaluate whether ejection dynamics, particularly acceleration time (AT) and the ratio of AT to ejection time (ET), can differentiate prosthetic aortic valve (PAV) stenosis from controls and prosthesis patient mismatch (PPM). BACKGROUND: Diagnosing PAV stenosis, especially in mechanical valves, may be challenging and has significant clinical implications. METHODS: Doppler echocardiography was quantitated in 88 patients with PAV (44 mechanical and 44 bioprosthetic; age 63 +/- 16 years; valve size range 18 to 25 mm) of whom 22 patients had documented PAV stenosis, 22 had PPM, and 44 served as controls. Quantitative Doppler parameters included ejection dynamics (AT, ET, and AT/ET) and conventional PAV parameters. RESULTS: Patients with PAV stenosis had significantly lower effective orifice area (EOA) values and higher gradients compared with controls and PPM. Flow ejection parameters (AT and AT/ET) were significantly longer in the stenotic valves compared with PPM and controls (respective values for AT: 120 +/- 24 ms, 89 +/- 16 ms, and 71 +/- 15 ms; for AT/ET: 0.4, 0.32, and 0.3, p <= 0.001). Patients with PPM had gradients and ejection dynamics that were intermediate between normal and stenotic valves. Receiver-operator characteristic (ROC) curve analysis showed that AT and AT/ET discriminated PAV stenosis from PPM and controls (area under ROC curve = 0.92 and 0.88, respectively). Combining AT with the conventional Doppler velocity index gave the highest area under the curve of 0.98 but was not statistically different from that of AT alone (p = 0.12). A cutoff of AT = 100 ms had a sensitivity and specificity of 86% for identifying PAV stenosis; for an AT/ET = 0.37, the sensitivity and specificity were 96% and 82%, respectively. Analysis by valve type (mechanical and biological) revealed similar results; however, biological valves had slightly higher areas under the curve for all systolic time intervals. CONCLUSIONS: Ejection dynamics through PAV, particularly AT and AT/ET, are reliable angle-independent parameters that can help evaluate valve function and identify PAV stenosis. PMID- 22093267 TI - Acute adverse reactions to gadolinium-based contrast agents in CMR: multicenter experience with 17,767 patients from the EuroCMR Registry. AB - OBJECTIVES: The purpose of this study was to assess the frequency, manifestation, and severity of acute adverse reactions associated with administration of several gadolinium-based contrast agents to patients who underwent cardiac magnetic resonance (CMR) imaging in the EuroCMR (European Cardiovascular Magnetic Resonance) Registry multinational and multicenter setting. BACKGROUND: The frequency, manifestations, and severity of acute adverse reactions associated with gadolinium-based contrast agents in the specific setting of cardiovascular magnetic resonance have not been systematically evaluated yet. METHODS: This is a multicenter and multinational registry with consecutive enrollment of patients in 45 European centers. During the current observation, 17,767 doses of gadolinium based contrast agent were administered to 17,767 patients. The mean dose was 25.6 ml (range 5 to 80 ml), which is equivalent to 0.128 mmol/kg (range 0.012 to 0.3 mmol/kg). RESULTS: Thirty acute adverse reactions due to contrast administration occurred (0.17%). All reactions were classified as mild according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (9 of 30), followed by nausea (7 of 30), and anxiety (6 of 30). The event rate ranged from 0.06% (linear nonionic agent gadodiamide) to 0.47% (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR imaging, ranging from 0.1% (risk stratification in suspected coronary artery disease) to 0.42% (viability in known coronary artery disease). CONCLUSIONS: The incidence of acute adverse reactions after administration of gadolinium-based contrast in the "off-label" setting of CMR in our population was not different from the incidence in the U.S. Food and Drug Administration-approved general radiology setting. Thus, the off-label use of gadolinium-based contrast in CMR should be regarded as safe concerning the frequency, manifestation, and severity of acute events. PMID- 22093268 TI - Acute adverse reactions to gadolinium in CMR: "gadol" news! PMID- 22093269 TI - Pericardial delayed hyperenhancement with CMR imaging in patients with constrictive pericarditis undergoing surgical pericardiectomy: a case series with histopathological correlation. AB - OBJECTIVES: The purpose of this study was to examine the prevalence and histopathologic correlates of pericardial delayed hyperenhancement (DHE) seen with cardiac magnetic resonance imaging (CMR) among patients with constrictive pericarditis (CP) undergoing pericardiectomy. BACKGROUND: Constrictive pericarditis patients studied by CMR will occasionally demonstrate pericardial DHE following gadolinium contrast administration. METHODS: We identified 25 CP patients who underwent pericardiectomy following CMR-gadolinium study. We also assessed 10 control subjects with no evidence of pericardial disease referred for cardiac viability imaging. A novel 14-segment pericardial model was used to determine pericardial DHE score and thickness score. Histopathology of pericardial specimens was reviewed and evaluated semiquantitatively on a 4-point scale for the extent of calcification, fibrosis, inflammation, and neovascularization. RESULTS: DHE was present in 12 (48%) CP patients (DHE+ group), and absent in 13 CP patients (DHE- group) and all control patients. The DHE+ group had greater fibroblastic proliferation and neovascularization, as well as more prominent chronic inflammation and granulation tissue. Fibroblastic proliferation and chronic inflammation correlated with DHE presence quantitated by DHE score (Spearman r = 0.578, p < 0.002, and r = 0.590, p < 0.002, respectively), but not with pericardial thickness. Segmental analysis demonstrated no significant difference in the percentage of patients with different pericardial segmental thickness; however, overall, in each segment, the DHE+ group tended to have greater pericardial thickness. CONCLUSIONS: The presence of pericardial DHE on CMR is common in patients with CP, and its presence is associated with histological features of organizing pericarditis, which may be a target for future focused pharmacological interventions. Patients with CP without pericardial DHE had more pericardial fibrosis and calcification, as well as lesser degrees of pericardial thickening. PMID- 22093270 TI - CMR imaging in constrictive pericarditis: is seeing believing? PMID- 22093271 TI - Prevalence and risk factors of carotid vessel wall inflammation in coronary artery disease patients: FDG-PET and CT imaging study. AB - OBJECTIVES: We investigated the prevalence and clinical risk factors of carotid vessel wall inflammation by means of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in a population consisting of coronary artery disease (CAD) patients. BACKGROUND: The atherosclerotic disease process is characterized by infiltration and retention of oxidized lipids in the artery wall, triggering a disproportionate inflammatory response. Efforts have been made to use noninvasive imaging to quantify this inflammatory response in the vessel wall. Recently, carotid FDG-PET has been shown to reflect the metabolic rate of glucose, a process known to be enhanced in inflamed tissue. METHODS: Carotid inflammation was quantified in 82 CAD patients (age 62 +/- 10 years) as the maximum target-to background ratio ((wholevessel)TBR(max)). Furthermore, we assessed the maximal standardized uptake value values ((wholevessel)SUV(max)), the single hottest segment (SHS), and the percent active segments (PAS) of the FDG uptake in the artery wall, measured by FDG-PET. RESULTS: Whole-vessel TBR(max) >1.8 was present in 67%, >2.0 in 39%, >2.2 in 23%, and >2.4 in 12% of the population. Multiple linear regression analysis with backward elimination revealed that body mass index (BMI) >=30 kg/m2 (p < 0.0001), age >65 years (p = 0.01), smoking (p = 0.02), and hypertension (p = 0.01) were associated with (wholevessel)TBR(max). The number of components of the metabolic syndrome was also associated with (wholevessel)TBR(max) (p = 0.02). In similar analyses, (wholevessel)SUV(max) was associated with BMI >=30 kg/m2 (p < 0.0001), age >65 years (p = 0.004), male gender (p = 0.02), and hypertension (p = 0.04); SHS with BMI >=30 kg/m2 (p < 0.0001), age >65 years (p = 0.02), smoking (p = 0.04), and hypertension (p = 0.05); PAS with BMI >=30 kg/m2 (p = 0.001), smoking (p = 0.03), and hypertension (p = 0.01). CONCLUSIONS: Carotid inflammation as revealed by FDG-PET is highly prevalent in the CAD population and is associated with obesity, age over 65 years, history of hypertension, smoking, and male gender. Artery wall FDG uptake increased when components of the metabolic syndrome clustered. PMID- 22093272 TI - Nephrogenic systemic fibrosis: review of 370 biopsy-confirmed cases. AB - Discovery of an association between gadolinium-based contrast agents (GBCAs) and nephrogenic systemic fibrosis (NSF) has led to less use of GBCA-enhanced magnetic resonance imaging in dialysis patients and patients with severe renal failure at risk of NSF, and the virtual elimination of new cases of NSF. But shifting patients with renal failure to alternative imaging methods may subject patients to other risks (e.g., ionizing radiation or iodinated contrast). This review paper examines 370 NSF cases reported in 98 articles to analyze NSF risk factors. Eliminating multiple risk factors by limiting GBCA dose to a maximum of 0.1 mmol/kg, dialyzing patients undergoing dialysis quickly following GBCA administration, delaying GBCA in acute renal failure until after renal function returns or dialysis is initiated, and avoiding nonionic linear GBCA in patients with renal failure especially when there are proinflammatory conditions may substantially reduce the risk of NSF. PMID- 22093273 TI - Mechanisms of very late stent thrombosis after drug-eluting stent implantation: findings from coronary angioscopy and optical coherence tomography. PMID- 22093274 TI - Sunflower artifact in OCT. PMID- 22093275 TI - Evolution and clinical importance of fibrosis in HCM. PMID- 22093276 TI - How should infarct size be measured on LGE sequences? A call for a change in the guidelines. PMID- 22093278 TI - ACC Imaging Council evolves into a section: a new opportunity for imagers. PMID- 22093279 TI - Coronary CT angiography: from sensitivity to specificity. PMID- 22093280 TI - Duration of temporary catheter use for hemodialysis: an observational, prospective evaluation of renal units in Brazil. AB - BACKGROUND: For chronic hemodialysis, the ideal permanent vascular access is the arteriovenous fistula (AVF). Temporary catheters should be reserved for acute dialysis needs. The AVF is associated with lower infection rates, better clinical results, and a higher quality of life and survival when compared to temporary catheters. In Brazil, the proportion of patients with temporary catheters for more than 3 months from the beginning of therapy is used as an evaluation of the quality of renal units. The aim of this study is to evaluate factors associated with the time between the beginning of hemodialysis with temporary catheters and the placement of the first arteriovenous fistula in Brazil. METHODS: This is an observational, prospective non-concurrent study using national administrative registries of all patients financed by the public health system who began renal replacement therapy (RRT) between 2000 and 2004 in Brazil. Incident patients were eligible who had hemodialysis for the first time. Patients were excluded who: had hemodialysis reportedly started after the date of death (inconsistent database); were younger than 18 years old; had HIV; had no record of the first dialysis unit; and were dialyzed in units with less than twenty patients. To evaluate individual and renal unit factors associated with the event of interest, the frailty model was used (N = 55,589). RESULTS: Among the 23,824 patients (42.9%) who underwent fistula placement in the period of the study, 18.2% maintained the temporary catheter for more than three months until the fistula creation. The analysis identified five statistically significant factors associated with longer time until first fistula: higher age (Hazard-risk - HR 0.99, 95% CI 0.99-1.00); having hypertension and cardiovascular diseases (HR 0.94, 95% CI 0.9-0.98) as the cause of chronic renal disease; residing in capitals cities (HR 0.92, 95% CI 0.9 0.95) and certain regions in Brazil - South (HR 0.83, 95% CI 0.8-0.87), Midwest (HR 0.88, 95% CI 0.83-0.94), Northeast (HR 0.91, 95% CI 0.88-0.94), or North (HR 0.88, 95% CI 0.83-0.94) and the type of renal unit (public or private). CONCLUSION: Monitoring the provision of arteriovenous fistulas in renal units could improve the care given to patients with end stage renal disease. PMID- 22093281 TI - Stigma experiences in bipolar patients: the impact upon functioning. AB - The aim of this study was to investigate the impact of self-rated stigma and functioning in patients with bipolar disorder in South Brazil. This is a cross sectional study. Sixty participants with bipolar disorder were recruited from an outpatient Bipolar Disorder Program. Experiences with and impact of perceived stigma were evaluated using the Inventory of Stigmatizing Experiences. Functional impairment was assessed with the Functioning Assessment Short Test (FAST). Higher scores of self-perceived stigma were correlated with higher FAST scores, indicating more disability. After linear correlation analysis, current depressive symptoms, age at onset of treatment, age at diagnosis and functioning were correlated with self-perceived stigma. The study demonstrated a correlation between stigma and poor functioning in bipolar disorder. Perceived stigma is really important to individuals with bipolar disorder, both to how they experience their illness and to its results on functioning. Potential consequences of such results for mental health care professionals are discussed. Differential clinical features, sociocultural factors and the sample size limit the generalization of the present findings. PMID- 22093282 TI - Crystal structure of guaiacol and phenol bound to a heme peroxidase. AB - Guaiacol is a universal substrate for all peroxidases, and its use in a simple colorimetric assay has wide applications. However, its exact binding location has never been defined. Here we report the crystal structures of guaiacol bound to cytochrome c peroxidase (CcP). A related structure with phenol bound is also presented. The CcP-guaiacol and CcP-phenol crystal structures show that both guaiacol and phenol bind at sites distinct from the cytochrome c binding site and from the delta-heme edge, which is known to be the binding site for other substrates. Although neither guaiacol nor phenol is seen bound at the delta-heme edge in the crystal structures, inhibition data and mutagenesis strongly suggest that the catalytic binding site for aromatic compounds is the delta-heme edge in CcP. The functional implications of these observations are discussed in terms of our existing understanding of substrate binding in peroxidases [Gumiero A et al. (2010) Arch Biochem Biophys 500, 13-20]. PMID- 22093283 TI - Protective effect of triphlorethol-A against ultraviolet B-mediated damage of human keratinocytes. AB - Ultraviolet B (UVB) radiation on human skin induces pathophysiological processes such as oxidative stress and inflammation. In previous reports, the antioxidant effects of triphlorethol-A were shown to protect cells against hydrogen peroxide induced cell damage and gamma ray-induced oxidative stress. In this study, the role of triphlorethol-A in protecting human keratinocytes (HaCaT) against UVB induced cell damage was investigated. Triphlorethol-A-treated cells were irradiated with UVB (150 mJ/cm(2)). Triphlorethol-A decreased UVB-induced intracellular ROS and restored the activities of antioxidant enzymes decreased by UVB radiation. Triphlorethol-A decreased UVB damage to cellular components, such as lipid membrane and DNA, restored cell viability and reduced UVB-induced apoptosis by inhibiting the mitochondria-mediated caspase pathway. Triphlorethol A also reduced the UVB-induced loss of DeltaPsi(m) and the active forms of caspase 9 and caspase 3. The anti-apoptotic effect of triphlorethol-A was found to involve the inhibition of c-Jun NH(2)-terminal kinase, which was induced by UVB exposure. And triphlorethol-A showed an absorptive capacity at range of UVB. These results suggest that triphlorethol-A protects human keratinocytes against UVB by enhancing the activities of the antioxidant system, inhibiting cellular damage and absorbing the UVB. PMID- 22093284 TI - Characterization of clinical response in patients with vitiligo undergoing autologous epidermal punch grafting. AB - BACKGROUND: Punch grafting is a well-established treatment for vitiligo, but predictive factors for outcomes are not well established. OBJECTIVE: To determine the characteristics of responses to punch grafting performed in patients with vitiligo. METHODS AND MATERIALS: Retrospective, single-center chart review. Response rates were assessed using photographs taken before and after grafting using a 1.5-mm punch instrument. Effectiveness of repigmentation was assessed using the following scale: worse, no improvement, 0% to 25% improvement, 25% to 50% improvement, 50% to 75% improvement, and 75% to 100% improvement. Repigmentation rates were correlated with patient demographics. RESULTS: Thirty seven charts were reviewed, from which data were available from 30 patients. The total number grafts was 606 in 44 transplanted areas; 87% (530/606) of the transplants survived, and 26 of the 30 (87%) patients achieved some degree of repigmentation. Patients younger than 20 achieved the greatest average improvement in repigmentation (mean 61%), whereas those aged 60 and older showed the least improvement (mean 38%). Punch grafting of the neck and trunk achieved the greatest repigmentation, with 65% and 63% average improvement, respectively. Acral sites and skin overlying joints improved the least. CONCLUSION: Punch grafting is successful in most patients with vitiligo, with an 87% graft survival rate, but the rates of repigmentation vary depending on clinical characteristics. PMID- 22093285 TI - Allyl isothiocyanate induced stress response in Caenorhabditis elegans. AB - BACKGROUND: Allyl isothiocyanate (AITC) from mustard is cytotoxic; however the mechanism of its toxicity is unknown. We examined the effects of AITC on heat shock protein (HSP) 70 expression in Caenorhabditis elegans. We also examined factors affecting the production of AITC from its precursor, sinigrin, a glucosinolate, in ground Brassica juncea cv. Vulcan seed as mustard has some potential as a biopesticide. FINDINGS: An assay to determine the concentration of AITC in ground mustard seed was improved to allow the measurement of AITC release in the first minutes after exposure of ground mustard seed to water. Using this assay, we determined that temperatures above 67 degrees C decreased sinigrin conversion to AITC in hydrated ground B. juncea seed. A pH near 6.0 was found to be necessary for AITC release. RT-qPCR revealed no significant change in HSP70A mRNA expression at low concentrations of AITC (< 0.1 MUM). However, treatment with higher concentrations (> 1.0 MUM) resulted in a four- to five-fold increase in expression. A HSP70 ELISA showed that AITC toxicity in C. elegans was ameliorated by the presence of ground seed from low sinigrin B. juncea cv. Arrid. CONCLUSIONS: * AITC induced toxicity in C. elegans, as measured by HSP70 expression.* Conditions required for the conversion of sinigrin to AITC in ground B. juncea seed were determined.* The use of C. elegans as a bioassay to test AITC or mustard biopesticide efficacy is discussed. PMID- 22093286 TI - Synergistic effects of antibiotics and an N-acyl homoserine lactone analog on Porphyromonas gingivalis biofilms. AB - AIMS: To investigate the effects of the combined application of an N-acyl homoserine lactone (HSL) analog and antibiotics on biofilms of Porphyromonas gingivalis, a major pathogen of periodontal disease. METHODS AND RESULTS: Antibiotics used were cefuroxime, ofloxacin and minocycline. A flow-cell model was used for biofilm formation. Samples were divided into four groups: control, analog-treated, antibiotic-treated and combined application groups. Biofilm cell survival was determined using adenosine triphosphate (ATP) bioluminescence and confocal laser microscopy (CLSM). In the combined application group, the ATP count in biofilm cells was significantly decreased compared with the antibiotic treated group (Games-Howell test, P < 0.05). A combination of cefuroxime and the analog was most effective against the P. gingivalis biofilm. CLSM observations revealed that the proportion of dead cells was highest in the combined application group. CONCLUSIONS: The combined application of the N-acyl HSL analog and antibiotics was effective at reducing the viability of P. gingivalis cells in biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: The combined application of the N acyl HSL analog and antibiotics may be successful for eradicating infections involving bacterial biofilms, such as periodontitis. PMID- 22093287 TI - Hepatic acute phase proteins--regulation by IL-6- and IL-1-type cytokines involving STAT3 and its crosstalk with NF-kappaB-dependent signaling. AB - The function of the liver as an important constituent of the immune system involved in innate as well as adaptive immunity is warranted by different highly specialized cell populations. As the major source of acute phase proteins, including secreted pathogen recognition receptors (PRRs), short pentraxins, components of the complement system or regulators of iron metabolism, hepatocytes are essential constituents of innate immunity and largely contribute to the control of a systemic inflammatory response. The production of acute phase proteins in hepatocytes is controlled by a variety of different cytokines released during the inflammatory process with IL-1- and IL-6-type cytokines as the leading regulators operating both as a cascade and as a network having additive, inhibitory, or synergistic regulatory effects on acute phase protein expression. Hence, IL-1beta substantially modifies IL-6-induced acute phase protein production as it almost completely abrogates production of acute phase proteins such as gamma-fibrinogen, alpha(2)-macroglobulin or alpha(1) antichymotrypsin, whereas production of for example hepcidin, C-reactive protein and serum amyloid A is strongly up-regulated. This switch-like regulation of IL-6 induced acute phase protein production by IL-1beta is due to a complex processing of the intracellular signaling events activated in response to IL-6 and/or IL 1beta, with the crosstalk between STAT3- and NF-kappaB-mediated signal transduction being of particular importance. Recent data suggest that in this context complex formation between STAT3 and the p65 subunit of NF-kappaB might be of key importance. The present review summarizes the regulation of acute phase protein production focusing on the role of the crosstalk of STAT3- and NF-kappaB driven pathways for transcriptional control of acute phase gene expression. PMID- 22093288 TI - Combination treatment using bipolar radiofrequency-based intense pulsed light, infrared light and diode laser enhanced clinical effectiveness and histological dermal remodeling in Asian photoaged skin. AB - BACKGROUND: Combined optical and bipolar radiofrequency (RF) devices have been effective for rejuvenation, but a single modality in one session cannot solve three-dimensional skin complaints, resulting in time-consuming visits. OBJECTIVE: To evaluate the safety and efficacy of single-session triple treatment using bipolar RF-based optical (intense pulsed light [IPL], infrared light, and diode laser) combination devices for treatment of photoaged Asian skin. MATERIALS AND METHODS: In a split-face trial, 11 women received four treatments at 3-week intervals consisting of the combination of sequential IPL, infrared light, and diode laser, all with RF, in one session. Outcome assessments included photography, global evaluation by blinded investigators, patient assessment, and objective biophysical measurements of color and elasticity. Punch biopsies were obtained from both sides of the face 1 month after the last treatment session. RESULTS: All patients showed statistically significant reduction in photoaging global score. Objective biophysical measurements showed significant improvements in melanin index and elasticity (R5, R7), as well as increases in the levels of procollagen type I and III and elastin. CONCLUSION: A combination of three different energy sources, with bipolar RF, in one session is effective without further downtime for solving multiple problems including tone, texture, and laxity observed in photoaged Asian skin. PMID- 22093289 TI - Emergence of an HIV-1 cluster harbouring the major protease L90M mutation among treatment-naive patients in Tel Aviv, Israel. AB - OBJECTIVE: Drug resistance-associated mutations (DRMs) among HIV-1 treatment naive patients have increased in recent years. Their incidence and prevalence in various exposure risk categories (ERCs) were evaluated. DESIGN: Plasma samples of HIV-1 treatment-naive patients diagnosed between 2001 and 2009 at the Tel Aviv Medical Center were screened for DRMs. METHODS: Samples obtained from patients following the HIV diagnosis were analysed retrospectively. Genotyping was carried out using the Trugene HIV-1 genotype kit (Siemens, Berkeley, CA, USA). Phylogenetic relationships among viral sequences were estimated using the maximum likelihood method. RESULTS: Thirty-eight of the 266 analysed sequences (14.3%) had DRMs, all occurring exclusively in the group of men who have sex with men (MSM). The rate of DRMs has constantly risen, reaching a peak of 21.9% in 2009. Notably, protease inhibitor (PI) DRMs became the most frequent DRMs in 2009. Phylogenetic analysis showed a tight cluster comprising 13 of 14 viruses harbouring the L90M major PI resistance mutation, suggesting a single infection source. CONCLUSION: There was an unexpectedly high rate of the major L90M PI resistance mutation in the MSM group. The clustered transmission of this mutation might be related to a high-risk sexual behaviour. Added to nonnucleoside reverse transcriptase inhibitor and nucleoside reverse transcriptase inhibitor resistance mutations, such a PI mutation may limit future therapeutic options for this particular patient population. PMID- 22093290 TI - Favorable outcome in a renal transplant recipient with donor-derived infection due to multidrug-resistant Pseudomonas aeruginosa. AB - Most cases of donor-derived infection due to Pseudomonas aeruginosa reported in the literature are associated with vascular dehiscence, all of which resulted either in death or graft failure requiring graft removal. We report the successful treatment of donor-derived infection due to multidrug-resistant P. aeruginosa in a 64-year-old male who presented with bacteremia and peritransplant renal fluid collection after undergoing deceased-donor renal transplantation. As a result of the report of positive donor cultures by the host Organ Procurement Organization, the infection was promptly identified by blood cultures drawn before appearance of symptoms. Surveillance blood cultures in recipients are not usually recommended. However, they should be done if donor cultures turn positive. Therefore, it is crucial to perform cultures in donors and to closely follow them up for early identification and prompt treatment of donor-transmitted infections due to organisms like P. aeruginosa that can be graft and/or life threatening. PMID- 22093291 TI - Evolution of human tuberculosis: a systematic review and meta-analysis of paleopathological evidence. AB - Tuberculosis is a re-emerging disease and is a major problem in both developing and developed countries today. An estimated one third of the world's population is infected and almost two million people die from the disease each year. Bone lesions occur in 3-5% of active tuberculosis cases and can be used to diagnose the disease in ancient skeletal remains. A meta-analysis was conducted on 531 palaeopathological tuberculosis cases from 221 sites (7250 BCE to 1899) on all continents for the purpose of testing two hypotheses; (1) the frequency of bone lesions does not change through time and (2) the distribution of lesions throughout the skeleton does not change over time. The frequency of bone lesions was found to significantly decrease over time (P<0.05). The distribution of bone lesions was found to change from mainly spinal in earlier time periods to include more cases in other regions of the skeleton (long bones, joints, hands, feet) in later time periods. This difference in distribution was evaluated using a Chi squared test and found to be significant (P<0.01). These findings are an important addition to the current knowledge of the evolution of the disease and the Mycobacterium tuberculosis. PMID- 22093292 TI - Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport. AB - The present study was to demonstrate the effects of goblet cell-targeting nanoparticles on the oral absorption of insulin in vitro, ex vivo and in vivo, and identify the targeting mechanism as well as the influence of mucus. The insulin loaded nanoparticles were prepared using trimethyl chitosan chloride (TMC) modified with a CSKSSDYQC (CSK) targeting peptide. Compared with unmodified nanoparticles, the CSK peptide modification could facilitate the uptake of nanoparticles in villi, enhance the permeation of drugs across the epithelium, meanwhile, induce a significantly higher internalization of drugs via clathrin and caveolae mediated endocytosis on goblet cell-like HT29-MTX cells. In transport studies across Caco-2/HT29-MTX co-cultured cell monolayer (simulating intestinal epithelium), the CSK peptide modification also showed enhanced transport ability, even if the targeting recognition was partially affected by mucus. Moreover, it was found the existence of mucus was propitious to the transport of insulin from both modified and unmodified nanoparticles. In the pharmacological and pharmacokinetic studies in diabetic rats, the orally administrated CSK peptide modified nanoparticles produced a better hypoglycemic effect with a 1.5-fold higher relative bioavailability compared with unmodified ones. In conclusion, CSK peptide modified TMC nanoparticles showed sufficient effectiveness as goblet cell-targeting nanocarriers for oral delivery of insulin. PMID- 22093294 TI - Re: Firas Abdollah, Maxine Sun, Jan Schmitges, et al. Cancer-specific and other cause mortality after radical prostatectomy versus observation in patients with prostate cancer: competing-risks analysis of a large North American population based cohort. Eur Urol 2011;60:920-30. PMID- 22093295 TI - Prognosis of T1G3 bladder cancer: how well can we predict progression? PMID- 22093296 TI - The challenges of harnessing new technology. PMID- 22093297 TI - Automated digital microfluidic sample preparation for next-generation DNA sequencing. AB - Next-generation sequencing (NGS) technology is a promising tool for identifying and characterizing unknown pathogens, but its usefulness in time-critical biodefense and public health applications is currently limited by the lack of fast, efficient, and reliable automated DNA sample preparation methods. To address this limitation, we are developing a digital microfluidic (DMF) platform to function as a fluid distribution hub, enabling the integration of multiple subsystem modules into an automated NGS library sample preparation system. A novel capillary interface enables highly repeatable transfer of liquid between the DMF device and the external fluidic modules, allowing both continuous-flow and droplet-based sample manipulations to be performed in one integrated system. Here, we highlight the utility of the DMF hub platform and capillary interface for automating two key operations in the NGS sample preparation workflow. Using an in-line contactless conductivity detector in conjunction with the capillary interface, we demonstrate closed-loop automated fraction collection of target analytes from a continuous-flow sample stream into droplets on the DMF device. Buffer exchange and sample cleanup, the most repeated steps in NGS library preparation, are also demonstrated on the DMF platform using a magnetic bead assay and achieving an average DNA recovery efficiency of 80%+/-4.8%. PMID- 22093298 TI - Functional cardiotoxicity profiling and screening using the xCELLigence RTCA Cardio System. AB - Cardiac safety testing of lead drug candidates is an important part of the drug discovery and development process. All new chemical entities need to be subjected to extensive preclinical assessment for cardiac liability, especially for a potentially fatal form of ventricular arrhythmia referred to as Torsades de Pointes. We have developed an innovative label-free, real-time system, the xCELLigence RTCA Cardio System, which is designed to monitor contractility of cardiomyocytes based on impedance measurement. The assay is performed using specially designed microtiter plates that are integrated with gold microelectrodes. The system was validated using mouse embryonic stem cell-derived cardiomyocytes, human-induced pluripotent stem cell-derived cardiomyocytes, and rat neonatal primary cardiomyocytes by applying a variety of tool compounds and drugs with known mechanisms of action. Our data show that the time resolution in the assay can provide important information about compound action. Furthermore, the impedance-based beating profile in response to compound treatment can provide mechanistic toxicity information regarding the target being modulated and may be able to flag pro-arrhythmic compounds. We believe the real-time and kinetic aspect of this technology combined with beat-to-beat measurement of cardiomyocyte contraction would make this instrument an important part of preclinical cardiac safety assessment. PMID- 22093299 TI - Strategies for implementing hardware-assisted high-throughput cellular image analysis. AB - Recent advances in imaging technology for biomedicine, including high-speed microscopy, automated microscopy, and imaging flow cytometry are poised to have a large impact on clinical diagnostics, drug discovery, and biological research. Enhanced acquisition speed, resolution, and automation of sample handling are enabling researchers to probe biological phenomena at an increasing rate and achieve intuitive image-based results. However, the rich image sets produced by these tools are massive, possessing potentially millions of frames with tremendous depth and complexity. As a result, the tools introduce immense computational requirements, and, more importantly, the fact that image analysis operates at a much lower speed than image acquisition limits its ability to play a role in critical tasks in biomedicine such as real-time decision making. In this work, we present our strategy for high-throughput image analysis on a graphical processing unit platform. We scrutinized our original algorithm for detecting, tracking, and analyzing cell morphology in high-speed images and identified inefficiencies in image filtering and potential shortcut routines in the morphological analysis stage. Using our "grid method" for image enhancements resulted in an 8.54* reduction in total run time, whereas origin centering allowed using a look up table for coordinate transformation, which reduced the total run time by 55.64*. Optimization of parallelization and implementation of specialized image processing hardware will ultimately enable real-time analysis of high-throughput image streams and bring wider adoption of assays based on new imaging technologies. PMID- 22093300 TI - Tissue dynamics spectroscopy for three-dimensional tissue-based drug screening. AB - Tissue dynamics spectroscopy combines dynamic light scattering with short coherence digital holography to capture intracellular motion inside multicellular tumor spheroid tissue models. The cellular mechanical activity becomes an endogenous imaging contrast agent for motility contrast imaging. Fluctuation spectroscopy is performed on dynamic speckle from the proliferating shell and hypoxic core to generate drug-response spectrograms that are frequency versus time representations of the changes in spectral content induced by an applied compound or an environmental perturbation. A combination of 28 reference compounds and conditions applied to rat osteogenic UMR-106 spheroids generated spectrograms that were crosscorrelated in a similarity matrix used for unsupervised hierarchical clustering of similar compound responses. This work establishes the feasibility of tissue dynamics spectroscopy for three-dimensional tissue-based phenotypic profiling of drug response as a fully endogenous probe of the response of tissue to reference compounds. PMID- 22093301 TI - Emerging clinical applications of microchip-based acoustophoresis. AB - Acoustophoresis is currently in a state of transition from the academic laboratories, moving into the biomedical laboratories and industries. Clear areas of interest are seen in clinical diagnostics and therapeutics, where new approaches to cell handling and purification are emphasized as highly potent areas. This article outlines some of the basic unit operations of acoustophoresis, where applications as cell washing, binary separation, free-flow acoustophoresis, and affinity acoustophoresis are highlighted. The most recent steps to move acoustophoresis into clinical and preclinical applications are also presented. PMID- 22093302 TI - Shrink-induced single-cell plastic microwell array. AB - The ability to interrogate and track single cells over time in a high-throughput format would provide critical information for fundamental biological understanding of processes and for various applications, including drug screening and toxicology. We have developed an ultrarapid and simple method to create single-cell wells of controllable diameter and depth with commodity shrink-wrap film and tape. Using a programmable CO(2) laser, we cut hole arrays into the tape. The tape then serves as a shadow mask to selectively etch wells into commodity shrink-wrap film by O(2) plasma. When the shrink-wrap film retracts upon briefly heating, high-aspect plastic microwell arrays with diameters down to 20 MUm are readily achieved. We calibrated the loading procedure with fluorescent microbeads. Finally, we demonstrate the utility of the wells by loading fluorescently labeled single human embryonic stem cells into the wells. PMID- 22093303 TI - A high-throughput microchromatography platform for quantitative analytical scale protein sample preparation. AB - Protein analysis (using either specific protein quantitation by methods such as HPLC and immunoassays or structural analysis by methods such as LC-MS) usually requires significant sample preparation, including quantitative purification of the target protein from complex sample matrices and potentially enzymatic treatment or labeling. We have developed platform for high-throughput microchromatography, capable of running 96 or more small volume samples in parallel, producing from 10 pg to 100 MUg of purified protein from each sample. The platform is based on disposable cartridge devices with 5 MUL packed bed of resin. The cartridges may be operated as spin columns or run on a modified 96 channel liquid handler with ultra-low dead volume syringes that directly connect to the cartridges, providing very precisely controlled positive-displacement flow control. A major application is quantitative purification of target proteins using affinity or physical chromatography. Using large diameter nonporous beads, standard microplate enzyme-linked immunosorbent assay reagents can be used to perform 30-min immunoassays. Enzymatic digestion methods have also been developed on the system for application in glycan profiling. PMID- 22093304 TI - Microfluidics enables small-scale tissue-based drug metabolism studies with scarce human tissue. AB - Early information on the metabolism and toxicity properties of new drug candidates is crucial for selecting the right candidates for further development. Preclinical trials rely on cell-based in vitro tests and animal studies to characterize the in vivo behavior of drug candidates, although neither are ideal predictors of drug behavior in humans. Improving in vitro systems for preclinical studies both from a technological and biological model standpoint thus remains a major challenge. This article describes how microfluidics can be exploited to come closer to this goal in combination with precision-cut liver slices (PCLS) as an improved organomimetic system. Recently, we developed a novel microfluidic based system incorporating a microchamber for slice perifusion to perform drug metabolism studies with mammalian PCLS under continuous flow. In the present study, the viability and metabolism of human PCLS were assessed by the measurement of the leakage of liver-specific enzymes and metabolism of four different substrates: lidocaine, 7-hydroxycoumarin, 7-ethoxycoumarin, and testosterone. All experiments were verified with well plates, an excellent benchmark for these experiments. Clearly, however, human tissue is not readily available, and it is worth considering how to perform a maximum number of informative experiments with small amounts of material. In one approach, the microfluidic system was coupled to an HPLC system to allow on-line monitoring and immediate detection of unstable metabolites, something that is generally not possible with conventional well-plate systems. This novel microfluidic system also enables the in vitro measurement of interorgan interactions by connecting microchambers containing different organ slices in series for sequential perfusion. This versatile experimental system has the potential to yield more information about the metabolic profiles of new drug candidates in human and animal tissues in an early stage of development compared with well plates alone. PMID- 22093305 TI - Let us remember and celebrate a very special person: James N. Little. PMID- 22093306 TI - A year of milestones. PMID- 22093307 TI - [Some thoughts about the modification of diagnostic criteria for acute respiratory distress syndrome]. PMID- 22093308 TI - [Blocking the spray of contaminants from patients' exhalent using a tracheal detecting bulb during endotracheal intubation]. AB - OBJECTIVE: To examine the effect of a newly-developed tracheal detecting-bulb (TDB) in preventing the spray of contaminants in patients' exhalent during emergency endotracheal intubation procedure. METHODS: 62 emergency patients (male or female, age 21-73 years, weight 47-83 kg, with different levels of consciousness and spontaneous breathing) were randomly divided into two groups (n =31 each) to receive endotracheal intubation by an anesthesiologist with more than 17 years of experience, with (TDB group) or without (control group) a TDB connected to the tracheal tubing. Records were taken regarding the patient's coughing, expansion / contraction of the TDB, the operator's feeling of the patient's exhalent on his face / neck and the contamination of these areas by blood / secretions from the patients in the due course. RESULTS: In TDB group, expansion / contraction of TDB occurred in all cases, but the operator felt no exhalent in any of them. In 9 cases the patients coughed but the operator was contaminated only in 2 cases. While in control group, the patients' exhalent was felt in 16 cases. Coughing were recorded in 7 cases, and the operator was contaminated in 11 cases. In comparison with the control group, TDB group had significantly lower(both P < 0.05), incidence in feeling the exhalent (0 vs. 16), and contamination by blood or secretions (2 vs. 11) although the two groups had no significant difference in the incidence of coughing (9 vs. 7, P > 0.05). CONCLUSION: TDB can play an important role in blocking the spray of contaminants in patients' exhalent during endotracheal intubation. PMID- 22093310 TI - [The role of heme oxygenase 1 in hydrogen peroxide induced apoptosis and mitochondrial trans membrane potential change in rat primary type II alveolar epithelium cells]. AB - OBJECTIVE: To understand the role of heme oxygenase-1 (HO-1) in hydrogen peroxide [H(2)O(2)] induced apoptosis and mitochondrial trans-membrane potential (MTMP) change in primary alveolar epithelial cell type II(AEC II). METHODS: Primary AEC II collected from healthy Sprague Dawley (SD) rats were cultured for 24 hours, then divided into four groups to be treated with: (1) saline; (2) H(2)O(2) (0.5 mmol/L); (3) H(2)O(2) +HO-1 (0.2 mmol/L); (4) H(2)O(2) +zinc original porphyrin IX (HO-1 inhibitor, 20 MUmol/L). The morphology of cells in the cultures was examined by fluorescent microscopy 2.5 hours later, and the number of apoptotic cells / the MTMP determined by flow-cytometry 0.5, 1.0, 1.5, 2.0 and 2.5 hours later. RESULTS: Large number of cells in with green (early apoptotic) or red (later apoptotic) fluorescence were observed by microscope in cultures treated with H(2)O(2) , and H(2)O(2) + HO-1 inhibitor, but such cells were obviously fewer in HO-1 treated cultures. Compared with saline treated cells, H(2)O(2) treated cells had significantly higher apoptosis rate, that increased with time, reaching peak value 2.5 hours into the treatment [0.5 hour: (30.27 +/- 0.74)% vs. (3.76 +/- 0.81)%, 2.5 hours: (40.46 +/- 0.91)% vs. (22.74 +/- 0.60)%, both P < 0.05], while the rate of MTMP depolarization was significantly lower (0.99 +/- 0.21 vs. 1.91 +/- 0.16, P < 0.05) in these cells. Compared with H(2)O(2) treated cells, the apoptosis rate in HO-1 treated cells was significantly lower [0.5 hour: (5.99 +/- 0.60)% vs. (30.27 +/- 0.74)%, 2.5 hours: (22.69 +/- 1.69)% vs. (40.46 +/- 0.91)%, both P < 0.05], and their rate of MTMP depolarization higher (2.02 +/- 0.12 vs. 0.99 +/- 0.21, P < 0.05). Compared with HO-1 treated cells, HO 1 inhibitor treated cells had significantly higher apoptosis rate which reached peak value 2.5 hours into the treatment [0.5 hour: (30.73 +/- 1.08)% vs. (5.99 +/ 0.60)%, 2.5 hours: (41.38 +/- 0.57)% vs. (22.69 +/- 1.69)%, both P < 0.05], while rate of MTMP depolarization in these cells was significantly lower (0.98 +/ 0.09 vs. 2.02 +/- 0.12, P < 0.05). CONCLUSION: HO-1 could maintain the integrity of AEC II and stabilize their mitochondria membrane potential, protecting the cells from H(2)O(2) induced damage. PMID- 22093309 TI - [The effect of factor VII activating protease treatment on proliferation and collagen synthesis of cultured human pulmonary fibroblasts]. AB - OBJECTIVE: To examine the influence of factor VII-activating protease (FSAP) treatment on cell proliferation and collagen synthesis in human pulmonary fibroblasts (HPF). METHODS: Cultured HPF were treated with heparin (10 mg/L), platelet-derived growth factor-BB (PDGF-BB, 20 MUg/L), FSAP (12 mg/L), aprotinin (10 mg/L) separately and in different mixture. The proliferation of the HPF was determined by 5-bromodeoxyuridine (BrDU) incorporation. The collagen III mRNA was determined by real-time polymerase chain reaction (PCR), and its protein expression, as well as the phosphorylation of p42 / p44 mitogen activated protein kinase (MAPK) were both determined using Western blotting. RESULTS: PDGF BB significantly (all P < 0.05) induced cell proliferation (1.23 +/- 0.06 vs. 1.01 +/- 0.01 without heparin, 1.24 +/- 0.04 vs. 0.98 +/- 0.01 with heparin), collagen III mRNA transcription (1.79 +/- 0.02 vs. 1.00 +/- 0.00 without aprotinin, 1.57 +/- 0.01 vs. 1.00 +/- 0.00 with aprotinin), and collagen III protein expression (0.54 +/- 0.26 vs. 0.17 +/- 0.05 without aprotinin, 0.59 +/- 0.31 vs. 0.24 +/- 0.15 with aprotinin) in HPF. PDGF BB also significantly (both P < 0.05) induced p42 / p44 MAPK phosphorylation in HPF (0.89 +/- 0.24 vs. 0.51 +/- 0.17 without aprotinin, 0.97 +/- 0.41 vs. 0.37 +/- 0.05 with aprotinin). In the presence of heparin FSAP significantly (all P < 0.05) inhibited the PDGF BB induced HPF proliferation (0.92 +/- 0.23 vs 1.19 +/- 0.11); collagen III mRNA transcription (0.61 +/- 0.02 vs. 1.79 +/- 0.02) and collagen III protein expression (0.15 +/- 0.12 vs. 0.54 +/- 0.26). FSAP also inhibited PDGF induced p42 / p44 MAPK phosphorylation in HPF (0.57 +/- 0.16 vs. 0.89 +/- 0.24) significantly (P < 0.05). The presence of aprotinin lead to a reversal of the inhibitory effect of FSAP on collagen III mRNA transcription (2.37 +/- 0.21 vs.0.61 +/- 0.02), collagen III protein expression (0.55 +/- 0.24 vs. 0.15 +/- 0.12) and p42 / p44 MAPK phosphorylation (0.86 +/- 0.41 vs. 0.57 +/- 0.16, all P < 0.05). CONCLUSION: FSAP could inhibit the PDGF-BB induced proliferation and collagen III synthesis in HPF in vitro through the suppression of p42 / p44 MAPK phosphorylation. PMID- 22093311 TI - [Enoxaparin for the prevention of post surgical pulmonary embolism]. AB - OBJECTIVE: To evaluate the efficacy and safety of the administration of enoxaparin, a low molecular weight heparin (LMWH), in the prevention of post surgical deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: 1928 patients hospitalized for general surgery were randomly divided into: (1) test group (n = 960) to receive enoxaparin (40 mg, s.c., 12 hours before and after surgery, then once daily for 7 consecutive days); (2) control group (n = 968) without intervention. The incidence of DVT,PE and bleeding were recorded for statistical analysis during hospitalization and a 2 months follow-up after discharge. RESULTS: (1) No significant difference was found between the two groups in age, sex, average body mass index, type of surgery, and DVT / PE risk factors (obesity, varicose veins, and history of: venous thrombosis, chronic obstructive pulmonary disease, chronic heart failure, and hormone therapy). The percentage of non-malignant / malignant tumor surgery were 36.5% / 63.5% (average operation time 2.3 hours) in control group and 35.6% / 64.4% (2.2 hours) in test group (both P > 0.05). (2) During the hospitalization period, 59 cases (incidence=6.1%) of DVT and 14 cases (incidence=1.4%) of PE (among them 6 were fetal, 42.8% of all PE cases) were found in the control group, while 28 cases of DVT (2.9%) and 3 cases (0.3%) of PE (1 fetal, 33.3% of all PE cases) were found in test group. The incidence of DVT, PE (total), and PE (fetal) were significant lower in test group (P < 0.05 or P < 0.01). During the follow up, 14 more cases of DVT (1.4%) and 1 more case (0.1%) of PE (a fetal) were found in the control group, and 2 more DVT cases (0.2%) in test group, with the DVT incidence in test group significantly lower (P < 0.01). (3) During the enoxaparin administration, 30 cases (3.1%) minor bleeding and 8 cases (0.8%) major bleeding were found in the control group, while 33 cases (3.4%) minor bleeding events and 9 cases (0.9%) major bleeding events were found in the test group. THE RESULTS: in the two groups were not significantly different in either type of bleeding events (both P > 0.05). Also no significant difference was found in the bleeding events after the ending of enoxaparin administration and during the follow up. CONCLUSION: Enoxaparin may reduce the incidence of DVT and PE in patients undergoing general surgery without increased risk of bleeding. PMID- 22093312 TI - [Evaluation of the hemodynamic state of critically ill cancer patients with central venous to arterial carbon dioxide difference]. AB - OBJECTIVE: To evaluate the hemodynamic state of critically ill cancer patients using central venous-to-arterial carbon dioxide difference (Pcv-aCO(2)) and to direct the treatment. METHODS: Clinical data of 47 cancer critically ill patients with acute physiology and chronic health evaluation II (APACHE II) score> 15 and unstable hemodynamic state were enrolled from intensive care unit of Tianjin Medical University Cancer Hospital from October 1st 2010 to May 31th 2011, were analyzed retrospectively. The patients were receiving the standard treatment according to the guidelines for 24 hours, the end-point of therapy was the standard of early goal direct therapy (EGDT). According to difference of sequential organ failure scores (DeltaSOFA) of that after treatment and before treatment, the patients were divided into two groups: DeltaSOFA<= 1 (n = 27) and DeltaSOFA> 1 (n = 20). The mean arterial pressure (MAP), urine output per hour, central venous pressure (CVP), oxygen saturation of central venous blood (ScvO(2)), the clearance of lactic acid, and Pcv-aCO(2) before treatment were compared with those after treatment, and their correlation with DeltaSOFA was analysed. RESULTS: There were no significant differences in MAP (mm Hg, 1 mm Hg = 0.133 kPa: 54.48 +/- 4.95 vs. 54.45 +/- 4.30), urine output per hour (ml:19.33 +/ 4.53 vs. 20.55 +/- 5.54), CVP(mm Hg: 3.48 +/- 1.81 vs. 3.25 +/- 1.16), ScvO(2) (0.571 +/- 0.042 vs. 0.578 +/- 0.047) of two groups before treatment (all P > 0.05), but in the group DeltaSOFA<=1, the Pcv-aCO(2) (mm Hg: 7.80 +/- 2.20 vs. 9.39 +/- 0.97) and SOFA scores (6.33 +/- 2.11 vs. 9.50 +/- 1.24) were significantly lower than those of the group DeltaSOFA>1 (all P < 0.01). There were no significant differences in MAP (mm Hg: 73.48 +/- 6.12 vs. 71.30 +/- 7.30), CVP (mm Hg: 6.85 +/- 1.26 vs. 6.50 +/- 1.28), ScvO(2) (0.693 +/- 0.032 vs. 0.684 +/- 0.039) between two groups after treatment (all P > 0.05), though their RESULTS: data were improved compared with that of before treatment. However, there were significant differences in Pcv-aCO(2) (mm Hg: 3.02 +/- 1.59 vs. 8.21 +/- 2.23), urine output per hour (ml: 71.41 +/- 6.74 vs. 51.70 +/- 7.50), SOFA score (6.03 +/- 2.56 vs. 10.05 +/- 1.61), the clearance of lactic acid [(27.71 +/ 11.46)% vs. -(0.78 +/- 13.29)%, all P < 0.01]. There was significant correlation between urine output per hour, Pcv-aCO(2), clearance of lactic acid and DeltaSOFA (r values were -0.712, 0.745, -0.631, all P < 0.05). CONCLUSION: Pcv-aCO(2) could be used as an index of evaluating the cardiac index and the hemodynamic state, and it could be considered to be one of the indices of evaluating the therapeutic effect and prognosis. PMID- 22093313 TI - [The effect of changes in the level of sex hormone on prognosis of abdominal surgical systemic inflammatory response syndrome]. AB - OBJECTIVE: To examine if the serum level of 3 sex hormones early after admission are correlated with the prognosis in post-abdominal surgery patients with systemic inflammatory response syndrome (SIRS). METHODS: 39 patients admitted to our surgical intensive care unit (SICU) for abdominal surgery were divided, according to their serum level of estradiol (E2), prolactin (PRL), and testosterone (TT), into: (1) E2 elevation group (n = 20), (2) E2 normal group (n = 19), (3) PRL elevation group (n = 16), (4) PRL normal group (n = 23), (5) TT reduction group (n = 14), and (6) TT normal group (n = 25), for data collection of: acute physiology and chronic health evaluation II(APACHE II) scores, total hospitalization days, ICU stay, total hospitalization cost and 28 day outcomes. RESULTS: In comparison with corresponding normal group, E2 elevation group had lower (but not statistically significant) APACHE II score (11.6 +/- 7.8 vs. 15.2 +/- 8.8, P > 0.05), significantly shorter ICU stay (days: 8.5 +/- 4.0 vs. 12.1 +/ 7.9, P < 0.05), and significantly lower 28 days mortality rate (10.0% vs. 35.7%, P < 0.05); PRL elevation group had significantly shorter ICU stay (days: 8.7 +/- 3.1 vs. 12.9 +/- 2.1, P < 0.01), and significantly lower total hospitalization cost (thousand yuan: 6.70 +/- 3.50 vs. 13.20 +/- 8.20, P < 0.05); TT reduction group had significantly lower APACHE II score (10.4 +/- 5.4 vs. 15.2 +/- 9.4, P < 0.05), significantly shorter ICU stay (days: 26.6 +/- 12.2 vs. 28.1 +/- 17.0, P < 0.01), and significantly lower 28-day mortality rate (0 vs. 31.8%, P < 0.01). CONCLUSION: The early serum levels of sex hormones may have significant influence on the prognosis in post-abdominal surgery patients with SIRS. PMID- 22093314 TI - [Changes in peripheral dendritic cells in serious burn patients and its clinical significance]. AB - OBJECTIVE: To explore the changes in peripheral dendritic cells (DCs) in serious burn patients and its relationship with the burn severity and pathogenesis of sepsis. METHODS: Twenty-two serious burn patients were divided into the burn group (n = 10) and the burn sepsis group (n = 12) according to diagnostic criteria of sepsis, they were stratified according to the total burn surface area (TBSA), into the TBSA I group (TBSA 30%-50%, n = 14) and the TBSA II group (TBSA 51%-80%, n = 8). Peripheral blood of all patients was collected on 1, 3, 7 ,14 ,20 day after burn. The number of two subtypes of peripheral DC i. e myeloid dendritic cells [mDC, Lineage1(-)HLA-DR(+)CD11c(+)] and plasmacytoid dendritic cells [pDC, Lineage1(-)HLA-DR(+)CD123(+)] were quantified by flow cytometer. Ten healthy volunteers served as normal controls at the same time. RESULTS: In the healthy control group, mDC in the peripheral blood was (0.450 +/- 0.150)% and pDC was (0.241 +/- 0.084)%. Compared with the healthy control group, in the burn group both mDC [(0.257 +/- 0.116)%, (0.274 +/- 0.086)%, (0.317 +/- 0.056)%] and pDC [(0.122 +/- 0.058)%, (0.165 +/- 0.051)%, (0.177 +/- 0.024)%] decreased significantly on 1, 3, 7 day after burn (all P < 0.05), and the number returned to the normal level on 14 day and 20 day. Compared with the burn group, the number of mDC [(0.230 +/- 0.090)%] and pDC [(0.114 +/- 0.071)%] in patients of the burn sepsis group were significantly lower (both P < 0.05) on 1 day after burn. Both cells [mDC (0.246 +/- 0.076)% vs. (0.412 +/- 0.097)% and pDC (0.097 +/ 0.032)% vs. (0.203 +/- 0.039)%] were still significantly lower (both P < 0.05) on 20 day. Both mDC [(0.266 +/- 0.062)%, (0.289 +/- 0.071)%, (0.351 +/- 0.054)%] and pDC [(0.131 +/- 0.025)%, (0.163 +/- 0.037)%, (0.178 +/- 0.038)%] in the patients in the TBSA I group decreased significantly on 1, 3, 7 day after burn as compared with those of the healthy control group(all P < 0.05), and they returned to the normal level on 14 day and 20 day. Compared with the TBSA I group, mDC [(0.227 +/- 0.070)%] and pDC [(0.112 +/- 0.047)%] in patients of the TBSA II group decreased significantly(both P < 0.05)on 1 day after burn, and both cells [mDC (0.297 +/- 0.072)% vs. (0.423 +/- 0.046)% and pDC (0.107 +/- 0.061)% vs.(0.197 +/- 0.042)%] were still significantly lower (both P < 0.05) on 20 day. CONCLUSION: Both the number of mDC and pDC decrease in peripheral blood in early stage in serious burn patients, and those who have more serious burn have lower number of mDC or pDC. Deficiency in mDCs and pDC subsets may contribute to immunosuppression in burn victims, and those who suffered obvious loss of mDC and pDC are susceptible to sepsis following severe burn. It indicates that the percentage of mDC and pDC can be a predictive index of sepsis after burn. PMID- 22093316 TI - [Changes in pulmonary metalloprotein-9 level in rats during sepsis, and the effect of ulinastatin]. PMID- 22093315 TI - [Device associated infection in medical surgical intensive care unit inpatients of an A level, tertiary class hospital in Beijing]. AB - OBJECTIVE: To understand the situation of the device-associated infection (DAI) in the medical-surgical intensive care unit(ICU)inpatients in an A-level tertiary class hospital in Beijing. METHODS: DAI date were collected through a surveillance on the medical-surgical ICU inpatients in an A-level tertiary class hospital in Beijing from January 2008 to December 2010. RESULTS: In 2279 patients admitted to the medical-surgical ICU (with a 15,332 days total hospitalization stay), 283 were found infected. The incidence for in-hospital infection was 12.42%, and 2.452% for the incidence per patient-day. The device utilization ratios for ventilator, central venous catheter and urinary catheter were 56.76%, 59.01% and 80.07% respectively while the incidence for ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) were 1.632%, 0.409% and 0.350% respectively. The predominant bacteria species found in these cases were Gram-negatives and the main stay of pathogenic species were A. baumannii, P. aeruginosa, Staphylococcus, E. coli, K. pneumoniae and C. albicans etc. CONCLUSION: The incidence of DAI in the surveyed hospital is close to other hospitals in China and other developing countries but higher than hospitals in United States. More efforts should be made for its prevention / control by hospital stuff, with the cooperation from the patients. PMID- 22093317 TI - [The safety of bronchoscope guided implantation of 2 double-lumen balloon micro catheter in the treatment of pulmonary hemoptysis: the factors involved]. PMID- 22093318 TI - [Clinical study of the incidence of sinusitis with tracheal intubation and its relation to duration of intubation]. PMID- 22093319 TI - [The mechanisms for the lung tissue protective effects of hydrogen : recent progress in mice study]. PMID- 22093320 TI - [Multiple organ dysfunction syndrome and related genetic polymorphisms]. PMID- 22093321 TI - Non-invasive diagnostic criteria for hepatocellular carcinoma: the value of contrast washout at imaging and the death of alpha-fetoprotein. PMID- 22093322 TI - Dilemma of recurrence of hepatitis B infection after liver transplantation. PMID- 22093323 TI - Autoimmune hepatitis from the paediatric perspective. AB - Autoimmune hepatitis (AIH) is an important entity within the broad spectrum of autoimmune hepatobiliary disease comprised of AIH, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since the 1960s, AIH has been investigated with extensive clinical research aimed at effective therapeutic intervention. It was one of the first liver diseases where treatment was demonstrated to prolong survival. AIH occurs in children, as well as in adults. Its clinical manifestations in children may differ from classic adult AIH. These differences have elucidated certain aspects of AIH and hepatobiliary disease in general. There are two major patterns of AIH: type 1, with anti-smooth muscle antibodies and type 2, with anti-liver/kidney microsomal antibodies. The second type of AIH was first identified in children and is more common in younger patients. AIH often presents as acute disease in children and also in adults: the nomenclature has dropped the allusion to chronicity. Some children who have sclerosing cholangitis present with clinical disease closely resembling AIH; this AIH-like PSC, termed autoimmune sclerosing cholangitis (ASC), is also found in adults. Children with AIH may have identifiable monogenic disorders of immune regulation such as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Like adults with AIH, children with AIH usually respond very favourably to immunosuppressive treatment with corticosteroids +/- azathioprine. True cures seem to be rare, although many children achieve a stable remission. Nonetheless children with AIH may develop cirrhosis and some require liver transplantation. Early diagnosis and improved treatment strategies may further improve the outlook for children with AIH. PMID- 22093325 TI - Previous overt hepatic encephalopathy rather than minimal hepatic encephalopathy impairs health-related quality of life in cirrhotic patients. AB - BACKGROUND: It has been observed that overt hepatic encephalopathy (HE) is accompanied by a persistent cognitive defect, suggesting that HE may not be fully reversible. The health-related quality-of-life (HRQoL) has been shown to be impaired by cirrhosis, and, according to some reports, influenced by minimal HE. Little is known about the effect of previous HE on HRQoL. AIM: To investigate the relative impact of previous HE and minimal HE on HRQoL in a group of consecutively hospitalized cirrhotic patients. PATIENTS/METHODS: Seventy five consecutive cirrhotic patients were evaluated using the Psychometric HE Score (PHES) and simplified Psychometric HE Score (SPHES) to detect the presence of minimal HE and using SF-36 to assess the HRQoL, both corrected for age and education. Eighteen of them had previous bouts of overt HE. RESULTS: Minimal HE was significantly more frequent in patients with previous HE than in those without (p < 0.001), independently on the method used for the diagnosis (PHES or SPHES). A deeper impairment in several domains of SF-36 was observed in patients with previous bouts of overt HE, in those with ascites, as well as in those with decompensated cirrhosis. At multivariate analysis, ascites, MELD score and previous HE were independently related to the mental-component-summary (MCS) of SF-36, whereas ascites was the only variable independently associated with the physical-component-summary (PCS) of SF-36. Minimal HE (independently on the method used for its diagnosis) impaired only one domain of SF-36. CONCLUSIONS: These data suggest that previous bouts of HE, despite their complete clinical resolution, play an independent role in producing a persistent impairment in HRQoL of cirrhotics. PMID- 22093324 TI - Antioxidants as therapeutic agents for liver disease. AB - Oxidative stress is commonly associated with a number of liver diseases and is thought to play a role in the pathogenesis of chronic hepatitis C, alcoholic liver disease, non-alcoholic steatohepatitis (NASH), haemochromatosis and Wilson's disease. Antioxidant therapy has thus been considered to have the possibility of beneficial effects in the management of these liver diseases. Despite this promise, antioxidants have produced mixed results in a number of clinical trials of efficacy. This review summarizes the results of clinical trials of antioxidants as sole or adjuvant therapy of chronic hepatitis C, alcoholic liver disease and non-alcoholic steatohepatitis (NASH). Overall, the most promising results to date are for vitamin E therapy of NASH but some encouraging results have been obtained with antioxidant therapy of acute alcoholic hepatitis as well. Despite evidence for small reductions of serum alanine aminotransferase, there is as yet no convincing evidence that antioxidant therapy itself is beneficial to patients with chronic hepatitis C. Problems such as small sample size, short follow up duration, inadequate endpoints, failure to demonstrate tissue delivery and antioxidant efficacy, and heterogeneous nature of the 'antioxidant' compounds used have complicated interpretation of results of the clinical studies. These limitations and their implications for future trial design are discussed. PMID- 22093326 TI - Long-term virological follow up of patients with occult hepatitis C virus infection. AB - BACKGROUND: Patients with occult hepatitis C virus (HCV) infection (HCV-RNA in liver without detectable anti-HCV and serum HCV-RNA) may have viral RNA in peripheral blood mononuclear cells (PBMCs) and in serum after ultracentrifugation, and may present HCV-specific T-cell responses, but it is unknown whether these markers persist to be detectable over time. AIM: To perform a prospective virological long-term follow up of patients with occult HCV. METHODS: Viral markers were tested every 3-4 months during 55.7 +/- 20.3 months in 37 patients with occult HCV who were under ursodeoxycholic acid treatment. RESULTS: Viral RNA was detectable in PBMCs of 31 patients during the follow up. In 23 of them, viral RNA in PBMCs was detected intermittently and in the other eight patients HCV-RNA was positive in a single sample. After ultracentrifugation, serum HCV-RNA was detected in 33 patients, being the viraemia intermittently detectable in 28, whereas in the remaining five patients, serum HCV-RNA was positive only once. Only one patient tested always HCV-RNA negative in PBMCs and in ultracentrifuged serum during follow up. Specific Core, NS3, and/or NS4 T-cell responses were found in 31 of the patients. The patient who was always HCV-RNA negative in PBMCs and in ultracentrifuged serum had specific HCV-T-cell responses. CONCLUSIONS: Occult HCV infection persists over time with fluctuating viraemia levels that induce and maintain specific T-cell responses against viral proteins. PMID- 22093327 TI - Long-term adefovir plus lamivudine therapy does not decrease creatinine clearance in HBeAg-negative chronic hepatitis B patients. AB - BACKGROUND/AIMS: As there are concerns about potential nephrotoxicity of nucleotide analogues, we evaluated renal function parameters during long-term adefovir and lamivudine combination therapy. METHODS: Forty-six HBeAg-negative patients with lamivudine-resistance treated with adefovir and lamivudine for up to 90 months were included. Renal function was assessed by estimated creatinine clearance (eC(CR) ) and compared with a matched control group of untreated inactive hepatitis B virus carriers. RESULTS: Serum HBV DNA became undetectable in 39 (85%) patients after a mean of 37 +/- 21 months. Three (6.5%) patients developed virological breakthrough. Adefovir resistance was detected in two patients. At the end of follow up, there was a significant decrease in mean eC(CR) (95 +/- 31-83 +/- 30 ml/min, P = 0.003) in the treated patients with 16% presenting aeC(CR) decrease >30%. Similar changes in eC(CR) were observed in the control group (108 +/- 28-96 +/- 26 ml/min, P = 0.003). In multiple regression analysis, age and baseline eC(CR) were independent predictors of eC(CR) reduction. CONCLUSIONS: Adefovir and lamivudine combination therapy is not an independent factor for significant renal dysfunction in HBeAg-negative patients with lamivudine-resistance. Baseline age and creatinine clearance are the only independent predictors of worsening renal function. PMID- 22093329 TI - Cirrhosis and a metallic foreign body in the stomach. PMID- 22093328 TI - NADPH oxidase-mediated platelet isoprostane over-production in cirrhotic patients: implication for platelet activation. AB - BACKGROUND: In patients with cirrhosis conflicting findings, inherent to platelet function and its clinical implication, are still matters of discussion. Cirrhosis is characterized by enhanced production of isoprostanes, index of oxidative stress in vivo, that is known to stem from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2)-generating oxidative stress and elicit platelet activation. AIM: To analyse the relationship between oxidative stress and platelet activation in cirrhosis. METHODS: A cross-sectional study including 51 cirrhotic patients and sex- and age-matched control patients has been designed. Soluble NOX2-derived peptide (sNOX2-dp), a direct marker of NADPH oxidase activation, isoprostanes urinary excretion, platelet isoprostanes and two markers of in vivo platelet activation, i.e. soluble CD40 Ligand (sCD40L) and soluble P-selectin (sPs), were measured. RESULTS: Compared with controls, cirrhotic patients had higher levels of sPs (P = 0.034), sCD40L (P < 0.0001), sNOX2-dp (P = 0.0016), urinary excretion of isoprostanes (P < 0.0001) and arachidonic acid-induced platelet isoprostane formation (P < 0.0001). A significant correlation between sNOX2-dp and platelet (R(s) = 0.39, P = 0.0051) and urinary (R(s) = 0.67, P < 0.0001) isoprostanes was detected; also, sNOX2-dp and isoprostanes significantly correlated with sPs and sCD40L. A stepwise regression analysis revealed that sNOX2-dp was independently related to sCD40L plasma levels. CONCLUSIONS: This study provides evidence that in cirrhosis, platelet isoprostanes are over-produced and could be implicated in platelet activation. PMID- 22093330 TI - Characterization of herpes simplex virus 1 strains as platforms for the development of oncolytic viruses against liver cancer. AB - BACKGROUND: Diverse oncolytic viruses (OV) are being designed for the treatment of cancer. The characteristics of the parental virus strains may influence the properties of these agents. AIMS: To characterize two herpes simplex virus 1 strains (HSV-1 17syn(+) and HFEM) as platforms for virotherapy against liver cancer. METHODS: The luciferase reporter gene was introduced in the intergenic region 20 locus of both HSV-1 strains, giving rise to the Cgal-Luc and H6-Luc viruses. Their properties were studied in hepatocellular carcinoma (HCC) cells in vitro. Biodistribution was monitored by bioluminescence imaging (BLI) in athymic mice and immune-competent Balb/c mice. Immunogenicity was studied by MHC-tetramer staining, in vivo killing assays and determination of specific antibody production. Intratumoural transgene expression and oncolytic effect were studied in HuH-7 xenografts. RESULTS: The H6-Luc virus displayed a syncytial phenotype and showed higher cytolytic effect on some HCC cells. Upon intravenous or intrahepatic injection in mice, both viruses showed a transient transduction of the liver with rapid relocalization of bioluminescence in adrenal glands, spinal cord, uterus and ovaries. No significant differences were observed in the immunogenicity of these viruses. Local intratumoural administration caused progressive increase in transgene expression during the first 5 days and persisted for at least 2 weeks. H6-Luc achieved faster amplification of transgene expression and stronger inhibition of tumour growth than Cgal-Luc, although toxicity of these non-attenuated viruses should be reduced to obtain a therapeutic effect. CONCLUSIONS: The syncytial H6-Luc virus has a strong oncolytic potential on human HCC xenografts and could be the basis for potent OV. PMID- 22093331 TI - Aquaporin-1 associated with hepatic arterial capillary proliferation on hepatic sinusoid in human cirrhotic liver. AB - BACKGROUND: Aquaporins (AQPs) are key regulators not only of water transport in the cytoplasm but also of angiogenesis. Although AQPs in the normal hepatobiliary system have been studied in mammals, little is known about the localization and changes of AQPs in the hepatic microvascular system including sinusoids in cirrhotic liver, which might contribute to portal hypertension. AIMS: We designed this study to examine the localization of AQP1 in human cirrhotic liver. METHODS: Surgical wedge biopsy specimens were obtained from non-cirrhotic portions of human livers (normal control) and from cirrhotic livers (LC) (Child A-LC and Child C-LC). Immunostaining, Western blotting, in situ hybridization (ISH) and laser-captured microdissection (LCM) were conducted. RESULTS: In control liver tissue, AQP1 was localized mainly in the portal venules, hepatic arterioles and bile ducts in the portal tract, although AQP1 was detected only slightly in the sinusoids. In cirrhotic liver tissue, AQP1 expression was evident, aberrantly observed on periportal sinusoidal endothelial cells corresponding to the capillarized sinusoids, on the proliferated arterial capillaries opening into the sinusoid in the generating hepatic nodule and on proliferated bile ductules at the peripheral edge of nodules and fibrotic septa. In cirrhotic liver, overexpression of AQP1 at protein and mRNA levels was demonstrated, respectively, using Western blot and ISH. AQP-1 of mRNA level in sinusoid was confirmed using LCM. CONCLUSIONS: Aberrant expressions of AQP1 in periportal sinusoidal regions in human cirrhotic liver indicate the proliferation of arterial capillaries directly connected to the sinusoids, contributing to microvascular resistance in cirrhosis. PMID- 22093332 TI - Involvement of cytosolic phospholipase A2 alpha signalling pathway in spontaneous and transforming growth factor-beta-induced activation of rat hepatic stellate cells. AB - BACKGROUND: Hepatic stellate cells (HSCs) are extracellular matrix-producing cells that play a pivotal role in liver fibrogenesis. During liver injury and when cells are placed in vitro, HSCs undergo phenotypic transition from quiescent retinoid-storing cells to activated retinoid-deficient myofibroblast-like cells. Although several mediators including reactive oxygen species, platelet derived growth factor, transforming growth factor-beta (TGF-beta) and tumour necrosis factor-alpha (TNF-alpha) were implicated in HSC activation, the cellular signalling pathways that regulate this process remain incompletely defined. AIMS: The objectives of this study were to evaluate the role of cytosolic phospholipase A(2) alpha (cPLA(2)alpha) and peroxisome proliferator-activated receptor beta/delta (PPAR-beta/delta) in HSC activation. METHODS: Rat HSCs were isolated, purified, cultured and stimulated with TGF-beta1 in the presence or absence of the selective cPLA(2)alpha inhibitor, arachidonyltrifluoromethyl ketone (AACOCF(3)). The activation status of HSC was evaluated by immunofluorescent staining of alpha-smooth muscle actin (alpha-SMA) and by measuring the expression of cPLA(2)alpha, cyclooxygenase 2 (COX-2) and PPAR-beta/delta using western blot analysis. RESULTS: Rapid and significant increase in cPLA(2)alpha expression was observed during activation of HSCs. These events preceded the elevation of PPAR beta/delta and the expression of alpha-SMA. Elevated expression of cPLA(2)alpha, but not COX-2, was also observed during TGF-beta-induced HSC activation. The TGF beta-induced alpha-SMA expression was blocked by AACOCF(3). Furthermore, transfection of a cPLA(2)alpha expression vector enhanced the transcription activity of PPAR-beta/delta and the expression of alpha-SMA in HSCs. CONCLUSION: cPLA(2)alpha-mediated induction of PPAR-beta/delta is a novel intracellular signalling pathway in spontaneous and TGF-beta induced activation of HSCs and could be a potential therapeutic target for the treatment of liver fibrosis. PMID- 22093333 TI - Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis. AB - BACKGROUND: Pattern recognition receptors (PRRs) orchestrate the innate immune defence in human biliary epithelial cells (BECs). Tight control of PRR signalling provides tolerance to physiological amounts of intestinal endotoxins in human bile to avoid constant innate immune activation in BECs. AIMS: We wanted to determine whether inappropriate innate immune responses to intestinal endotoxins contribute to the development and perpetuation of chronic biliary inflammation. METHODS: We examined PRR-mediated innate immune responses and protective endotoxin tolerance in primary BECs isolated from patients with primary sclerosing cholangitis (PSC), alcoholic liver disease and patients without chronic liver disease. Expression studies comprised northern blots, RT-PCR, Western blots and immunocytochemistry. Functional studies comprised immuno precipitation Western blots, FACS for endotoxin uptake, and NF-kappaB activation assays and ELISA for secreted IL-8 and tumour necrosis factor (TNF)-alpha. RESULTS: Primary BECs from explanted PSC livers showed reversibly increased TLR and NOD protein expression and activation of the MyD88/IRAK signalling complex. Consecutively, PSC BECs exhibited inappropriate innate immune responses to endotoxins and did not develop immune tolerance after repeated endotoxin exposures. This endotoxin hyper-responsiveness was probably because of the stimulatory effect of abundantly expressed IFN-gamma and TNF-alpha in PSC livers, which stimulated TLR4-mediated endotoxin signalling in BECs, leading to increased TLR4-mediated endotoxin incorporation and impaired inactivation of the TLR4 signalling cascade. As TNF-alpha inhibition partly restored protective innate immune tolerance, endogenous TNF-alpha secretion probably contributed to inappropriate endotoxin responses in BECs. CONCLUSION: Inappropriate innate immune responses to intestinal endotoxins and subsequent endotoxin intolerance because of enhanced PRR signalling in BECs probably contribute to chronic cholangitis. PMID- 22093334 TI - Hepatic iron overload following liver transplantation of a C282y homozygous allograft: a case report and literature review. AB - Hereditary haemochromatosis is a common genetic disease associated with progressive iron overload and parenchymal organ damage including liver, pancreas and heart. We report a case of inadvertent transplantation of a liver from a haemochromatosis donor to a 56-year-old Asian female. Progressive iron overload occurred over a 2 year follow up as assessed by liver biopsy and iron studies in the absence of a secondary cause of iron overload, supporting a primary role of liver rather than small intestine in the regulation of iron homeostasis in hereditary haemochromatosis. PMID- 22093335 TI - A novel Y231del mutation of HFE in hereditary haemochromatosis provides in vivo evidence that the Huh-7 is a human haemochromatotic cell line. AB - Hereditary haemochromatosis (HH), which is mainly associated with a C282Y polymorphism in HFE, is common among Caucasians of north European descent, but is very rare among Asians. Herein, we report a 43-year-old Japanese man who was diagnosed as having HH. A laboratory examination revealed an elevated serum iron level (280 MUg/dl), hyperferritinemia (1698 ng/ml) and a low serum level of hepcidin-25 (4.0 ng/ml). Abdominal magnetic resonance imaging revealed findings suggestive of iron accumulation in the liver and pancreas. HFE gene sequencing in the patient revealed a novel homozygous TAC nucleotide deletion (c. 691_693del) responsible for the loss of a tyrosine at position 231 (p. Y231del) of the HFE protein. This homozygous Y231del mutation was recently found in the Huh-7 hepatoma cell line and was shown to prevent the translocation of HFE to the cell surface. This clinical case provides in vivo evidence suggesting that Huh-7 is undoubtedly a human haemochromatotic cell line and, as such, is a valuable tool for investigating the pathogenesis of HFE-related HH in humans. PMID- 22093336 TI - Validation of fatty liver index and lipid accumulation product for predicting fatty liver in Korean population. PMID- 22093337 TI - Prevalence of cognitive impairment in individuals aged over 65 in an urban area: DERIVA study. AB - BACKGROUND: Few data are available on the prevalence of cognitive impairment (CI) in Spain, and the existing information shows important variations depending on the geographical setting and the methodology employed. The aim of this study was to determine the prevalence of CI in individuals aged over 65 in an urban area, and to analyze its associated risk factors. METHODS: DESIGN: A descriptive, cross-sectional, home questionnaire-based study; SETTING: Populational, urban setting. PARTICIPANTS: The reference population comprised over-65s living in the city of Salamanca (Spain) in 2009. Randomized sampling stratified according to health district was carried out, and a total of 480 people were selected. In all, 327 patients were interviewed (68.10%), with a mean age of 76.35 years (SD: 7.33). Women accounted for 64.5% of the total. MEASUREMENTS: A home health questionnaire was used to obtain the following data: age, sex, educational level, family structure, morbidity and functionality. All participants completed a neuropsychological test battery. The prevalence data were compared with those of the European population, with direct adjustment for age and sex. Diagnoses were divided into three general categories: normal cognitive function, cognitive impairment - no dementia (CIND), and dementia. RESULTS: The prevalence of CI among these over-65s was 19% (14.7% CIND and 4.3% dementia). The age-and sex adjusted global prevalence of CI was 14.9%. CI increased with age (p < 0.001) and decreased with increasing educational level (p < 0.001). Significant risk factors were found with the multivariate analyses: age (OR = 1.08, 95%CI: 1.03-1.12), anxiety-depression (OR = 3.47, 95%CI: 1.61-7.51) and diabetes (OR = 2.07, 95%CI: 1.02-4.18). In turn, years of education was found to be a protective factor (OR = 0.79, 95%CI: 0.70-0.90). Although CI was more frequent among women and in people living without a partner, these characteristics were not significantly associated with CI risk. CONCLUSIONS: The observed raw prevalence of CI was 19% (14.9% after adjusting for age and sex). Older age and the presence of diabetes and anxiety depression increased the risk of CI, while higher educational level reduced the risk. PMID- 22093338 TI - Microfluidics for the deposition of density gradients of immobilized oligonucleotide probes; developing surfaces that offer spatial control of the stringency of DNA hybridization. AB - A method for the development of continuous density gradients of immobilized oligonucleotide probes (20mer) along the length of microfluidic channels is demonstrated. The development of continuous density gradients was achieved using variable electrokinetic transport of probes in hybrid glass-polydimethylsiloxane microfluidic chips. The probes were terminated with an amine functional group, and were delivered by electrokinetic pumping to the flat glass channel wall after it had been densely coated with covalently immobilized aldehyde groups. This method provided probe immobilization densities ranging from 4.5(+/-0.8)*10(13) to 2.5(+/-0.8)*10(11) molecules cm(-2), with longitudinal dilution and differential mass transport of the injected plug of probes being the primary factors responsible for the gradient of density. The utility of the resulting density gradient of immobilized probes to control the selectivity of hybridization was demonstrated at room temperature by discrimination between a fully complementary oligonucleotide target, and a target strand containing 3 base pair mismatches (3 BPM) based on the spatial pattern of hybridization for sub-picomole quantities of targets. Single nucleotide polymorphism (SNP) discrimination was possible when temperature control was implemented to improve resolution of the mismatch discrimination, allowing SNP discrimination at 35 degrees C with a contrast ratio of almost 5 to 1. PMID- 22093339 TI - Applicability of multisyringe chromatography coupled to cold-vapor atomic fluorescence spectrometry for mercury speciation analysis. AB - In this paper, a novel automatic approach for the speciation of inorganic mercury (Hg(2+)), methylmercury (MeHg(+)) and ethylmercury (EtHg(+)) using multisyringe chromatography (MSC) coupled to cold-vapor atomic fluorescence spectrometry (CV/AFS) was developed. For the first time, the separation of mercury species was accomplished on a RP C18 monolithic column using a multi-isocratic elution program. The elution protocol involved the use of 0.005% 2-mercapthoethanol in 240 mM ammonium acetate (pH 6)-acetonitrile (99:1, v/v), followed by 0.005% 2 mercapthoethanol in 240 mM ammonium acetate (pH 6)-acetonitrile (90:10, v/v). The eluted mercury species were then oxidized under post-column UV radiation and reduced using tin(II) chloride in an acidic medium. Subsequently, the generated mercury metal were separated from the reaction mixture and further atomized in the flame atomizer and detected by AFS. Under the optimized experimental conditions, the limits of detection (3sigma) were found to be 0.03, 0.11 and 0.09 MUg L(-1) for MeHg(+), Hg(2+) and EtHg(+), respectively. The relative standard deviation (RSD, n=6) of the peak height for 3, 6 and 3 MUg L(-1) of MeHg(+), Hg(2+) and EtHg(+) (as Hg) ranged from 2.4 to 4.0%. Compared with the conventional HPLC-CV/AFS hyphenated systems, the proposed MSC-CV/AFS system permitted a higher sampling frequency and low instrumental and operational costs. The developed method was validated by the determination of a certified reference material DORM-2 (dogfish muscle), and was further applied for the determination of mercury species environmental and biological samples. PMID- 22093341 TI - Chemometric determination of the length distribution of single walled carbon nanotubes through optical spectroscopy. AB - Current synthesis methods for producing single walled carbon nanotubes (SWCNTs) do not ensure uniformity of the structure and properties, in particular the length, which is an important quality indicator of SWCNTs. As a result, sorting SWCNTs by length is an important post-synthesis processing step. For this purpose, convenient analysis methods are needed to characterize the length distribution rapidly and accurately. In this study, density gradient ultracentrifugation was applied to prepare length-sorted SWCNT suspensions containing individualized surfactant-wrapped SWCNTs. The length of sorted SWCNTs was first determined by atomic force microscope (AFM), and their absorbance was measured in ultraviolet-visible near-infrared (UV-vis-NIR) spectroscopy. Chemometric methods are used to calibrate the spectra against the AFM-measured length distribution. The calibration model enables convenient analysis of the length distribution of SWCNTs through UV-vis-NIR spectroscopy. Various chemometric techniques are investigated, including pre-processing methods and non linear calibration models. Extended inverted signal correction, extended multiplicative signal correction and Gaussian process regression are found to provide good prediction of the length distribution of SWCNTs with satisfactory agreement with the AFM measurements. In summary, spectroscopy in conjunction with advanced chemometric techniques is a powerful analytical tool for carbon nanotube research. PMID- 22093340 TI - Quantitative trace analysis of benzene using an array of plasma-treated metal decorated carbon nanotubes and fuzzy adaptive resonant theory techniques. AB - The functionalization of carbon nanotube sidewalls with metal nanoparticles is exploited here to improve the sensitivity and selectivity of gas sensors operated at room temperature. An array of sensors using oxygen plasma treated multiwalled carbon nanotubes (bare and decorated with Pt, Pd or Rh nanoparticles) is shown to selectively detect traces of benzene (i.e., 100 ppb) in the presence of carbon monoxide, hydrogen sulfide or nitrogen dioxide at different humidity levels. Employing a quantitative fuzzy adaptive resonant theory (ART) network whose inputs are the responses of the sensor array, it is possible to accurately estimate benzene concentration in a changing background. The quantitative fuzzy ART is especially suited for compensating the nonlinear effects in sensor response caused by changes in ambient humidity, which explains why this method clearly outperforms partial least squares calibration models at estimating benzene concentration. These results open the way to design new affordable, wearable, sensitive and selective detectors aimed at the personal protection of workers subject to occupational exposure to benzene, toluene, ethyl benzene and xylenes. PMID- 22093342 TI - Electrochemical sensors based on molecularly imprinted polymers grafted onto gold electrodes using click chemistry. AB - We have developed a three-step method to graft molecularly imprinted polymer (MIP) thin films onto Au electrodes. In the first step, propargyl acrylate is clicked onto an azidoundecanethiol (N(3)(CH(2))(11)SH)/decanethiol mixed self assembled monolayer (SAM). Then, by applying UV light (365 nm) in the presence of N,N'-methylenebis(acrylamide) (MAAM) and azobisisobutyronitrile (AIBN) as the radical initiator, polymerization was carried out directly on the electrode surface in the presence of an electroactive template molecule, hydroquinone (HQ). Detection of HQ using the clicked-on MIP sensor was studied using chronoamperometry and its behavior was compared to that of a sensor prepared by drop-coating MIPs onto Au. The detection limit of the clicked-on MIP sensor for HQ was found to be 1.21+/-0.56 MUM, about four times lower than what was observed using the coated-on MIP sensor. In addition, the sensitivity of the clicked-on MIP sensor was found to be approximately three times greater than the coated-on MIP sensor. Apparent diffusion coefficients determined using chronoamperometry suggest that the improved performance is likely due to the favorable mass transfer characteristics of the clicked-on MIP sensing membrane. PMID- 22093343 TI - A sensitive enzymeless hydrogen-peroxide sensor based on epitaxially-grown Fe3O4 thin film. AB - A novel and facile approach has been developed to synthesize thin films of magnetite (Fe(3)O(4)) with epitaxial needle-like columnar grains on titanium nitride (TiN) buffered substrate using DC magnetron reactive sputtering. TiN buffer layer was first sputtered onto a substrate at 550 degrees C as a preferable substrate for growth following sputtering of epitaxial crystalline Fe(3)O(4) at 300 degrees C. The as-synthesized epitaxial Fe(3)O(4) was extensively characterized. The electrocatalytic activity of the epitaxial Fe(3)O(4) thin-film sensor against hydrogen peroxide (H(2)O(2)) reduction was rapid with a response time less than 5 s. The sensor also exhibited an acceptable stability, a satisfying sensitivity of 432.2 MUA mM(-1) cm(-2), good specificity to the substrate, a dynamic working range of up to 0.7 mM and a low detection limit of 1.0 MUM. The sensor performance correlated well (R(2)=0.996) with results obtained using a commercial HPLC-UV device. The sensor performance was robust and accurate in measuring H(2)O(2) in some complex matrices. The advantages of relative simplicity and ease of mass production make the epitaxial Fe(3)O(4) thin film promising candidate for use in sensing applications. PMID- 22093344 TI - Optimization and evaluation of mixed-bed chemisorbents for extracting fission and activation products from marine and fresh waters. AB - Chemically selective chemisorbents are needed to monitor natural and engineered waters for anthropogenic releases of stable and radioactive contaminants. Here, a number of individual and mixtures of chemisorbents were investigated for their ability to extract select fission and activation product elements from marine and coastal waters, including Co, Zr, Ru, Ag, Te, Sb, Ba, Cs, Ce, Eu, Pa, Np, and Th. Conventional manganese oxide and cyanoferrate sorbents, including commercially available Anfezh and potassium hexacyanocobalt(II) ferrate(II) (KCFC), were tested along with novel nano-structured surfaces (known as Self Assembled Monolayers on Mesoporous Supports or SAMMS) functionalized with a variety of moieties including thiol, diphosphonic acid (DiPhos-), methyl-3,4 hydroxypyridinone (HOPO-), and cyanoferrate. Extraction efficiencies were measured as a function of salinity, organic content, temperature, flow rate and sample size for both synthetic and natural fresh and saline waters under a range of environmentally relevant conditions. The effect of flow rate on extraction efficiency, from 1 to 70 mL min(-1), provided some insight on rate limitations of mechanisms affecting sorption processes. Optimized mixtures of sorbent-ligand chemistries afforded excellent retention of all target elements, except, Ba and Sb. Mixtures of tested chemisorbents, including MnO(2)/Anfezh and MnO(2)/KCFC/Thiol (1-3 mm)-SAMMS, extracted 8 of the 11 target elements studied to better than 80% efficiency, while a mixture of MnO(2)/Anfezh/Thiol (75-150 MUm)-SAMMS mixture was able to extract 7 of the 11 target elements to better than 90%. Results generated here indicate that flow rate should be less of a consideration for experimental design if sampling from fresh water containing variable amounts of DOM, rather than collecting samples from salt water environments. Relative to the capability of any single type of chemisorbent tested, optimized mixtures of several sorbents are able to increase the number of elements that can be efficiently and simultaneously extracted from natural waters. PMID- 22093345 TI - Graphene-assisted matrix solid-phase dispersion for extraction of polybrominated diphenyl ethers and their methoxylated and hydroxylated analogs from environmental samples. AB - In this work, we developed a novel graphene-assisted matrix solid-phase dispersion (GA-MSPD) method for extraction of polybrominated diphenyl ethers (PBDEs) and their methoxylated (MeO-) and hydroxylated (OH-) analogs from environmental samples. We found that grinding the solid sample with chemically converted graphene (CCG) powder yielded a tight contact and sufficient dispersion of the sample matrix due to the large surface area and flexible nanosheet morphology of CCG. The resultant blend was eluted using a two-step elution strategy: PBDEs and MeO-PBDEs were eluted firstly by hexane/dichloromethane and analyzed by GC-ECD, and then OH-PBDEs were eluted by acetone and determined by LC ESI-MS/MS. The GA-MSPD conditions were optimized in detail. Better recoveries were obtained with GA-MSPD than with other sorbents (C18 silica, Florisil and carbon nanotubes) and other extraction techniques (Soxhlet and accelerated solvent extraction). Other advantages of GA-MSPD, including reduced consumption of sorbent and solvent, good selectivity and short extraction time, were also demonstrated. In analysis of soil samples, the method detection limits of five PBDEs, ten MeO-PBDEs and ten OH-PBDEs were in the range of 5.9-28.7, 14.3-46.6, and 5.3-212.6 pg g(-1) dry weight, respectively. The proposed method was successfully applied to the extraction of PBDEs, MeO-PBDEs and OH-PBDEs from different kinds of spiked environmental samples, including soil, tree bark and fish. PMID- 22093346 TI - Determination of trace impurities in cosmetic intermediates by ion mobility spectrometry. AB - The cosmetic and pharmaceutical industries are continuously demanding fast, efficient, cost-effective analytical methods to monitor production processes and assure end-product quality. The presence of residual reagents or impurities formed during a synthetic process can have an adverse impact on product quality, assurance of which requires using increasingly sensitive analytical methods to facilitate the detection and/or determination of toxic compounds with potentially hazardous effects on consumer's health. In this work, we assessed the potential of ion mobility spectrometry (IMS) for the detection and quantitation of dimethylaminopropylamine (DMAPA) residues in stearamidopropyldimethylamine (SAPDA) production samples. The influence of instrumental variables including solvent, solution drying time, injected volume and volatilization temperature was examined. The ensuing analytical method takes less than 1 min per analysis and uses only a few microlitres of sample. The calibration curve was linear over the DMAPA concentration range 0.030-0.500 MUg mL(-1). The proposed method was validated for use in control processes. The complex plasmagram for amidoamines allows the origin of cosmetic oils to be easily, expeditiously identified. Based on the results, IMS holds great promise for the qualitative and quantitative determination of the studied amide and various others in cosmetic products. PMID- 22093347 TI - Nanoparticle assembled microcapsules for application as pH and ammonia sensor. AB - The encapsulation of molecular probes in a suitable nanostructured matrix can be exploited to alter their optical properties and robustness for fabricating efficient chemical sensors. Despite high sensitivity, simplicity, selectivity and cost effectiveness, the photo-destruction and photo-bleaching are the serious concerns while utilizing molecular probes. Herein we demonstrate that hydroxy pyrene trisulfonate (HPTS), a pH sensitive molecular probe, when encapsulated in a microcapsule structure prepared via the assembly of silica nanoparticles mediated by poly-L-lysine and trisodium citrate, provides a robust sensing material for pH sensing under the physiological conditions. The temporal evolution under continuous irradiation indicates that the fluorophore inside the silica microcapsule is extraordinarily photostable. The fluorescence intensity alternation at dual excitation facilitates for a ratiometic sensing of the pH, however, the fluorescence lifetime is insensitive to hydrogen ion concentration. The sensing scheme is found to be robust, fast and simple for the measurement of pH in the range 5.8-8.0, and can be successfully applied for the determination of ammonia in the concentration range 0-1.2 mM, which is important for aquatic life and the environment. PMID- 22093348 TI - Simple and fast fluorescence detection of benzoyl peroxide in wheat flour by N methoxy rhodamine-6G spirolactam based on consecutive chemical reactions. AB - Benzoyl peroxide (BPO) as a brightener is often added to wheat flour, and excessive use of this food additive is receiving increasing concern. Herein, a simple and fast method for fluorescence detection of BPO is proposed based on consecutive chemical reactions. In this approach, BPO first oxidizes Fe(2+) into Fe(3+) and the resulting Fe(3+) then induces the opening of the spirolactam ring of a new rhodamine derivative, N-methoxy rhodamine-6G spirolactam, switching on fluorescence of the detection system. More importantly, the fluorescence response of the reaction system to BPO is rather rapid and sensitive, with a detection limit of 6 mg kg(-1) (k=3), which makes it to be of great potential use in food safety analysis. The applicability of the proposed method has been successfully demonstrated on the determination of BPO in wheat flour samples. PMID- 22093349 TI - Silver nanoparticle-treated filter paper as a highly sensitive surface-enhanced Raman scattering (SERS) substrate for detection of tyrosine in aqueous solution. AB - Highly sensitive SERS substrates based on deposition of silver nanoparticles on commercially available filter paper were prepared in this work, and used to overcome problems found in analyses of aqueous samples. To prepare silver nanoparticle- (AgNP) doped filter substrates, a silver mirror reaction was used. The procedures for substrate preparation were systematically optimized. Pretreatment of filter paper, reaction time, temperature, and concentration of reagents for silver mirror reactions were studied. The morphologies of the resulting substrates were characterized by field-emission scanning electron microscopy (FE-SEM) and correlated with the SERS signals by probing with p nitrothiophenol (pNTP). Filter papers with different pretreatments were found to have different sizes and distributions of AgNPs. The best performance was found when filter paper was pre-treated with ammonia solution before growth of AgNPs. Based on the SEM images, the resulting AgNPs had roughly spherical shape with a high degree of uniformity. The silver-coated filter paper substrates provide much higher SERS signals compared to glass substrates and the reproducibility was improved significantly. Based on statistical analyses, the relative standard deviations for substrate-to-substrate and spot-to-spot were both were less than 8% and the enhancement factors for the substrates were, in general, higher than 107. The SERS substrates were used to selectively detect tyrosine in aqueous solution. Results indicate that filter-based SERS substrates are highly suited to detection of tyrosine. Compared to glass-based SERS substrates, 50 times more SERS signal was observed in detection of tyrosine. The linear range can be up to 100 MUM with a detection limit of 625 nM (SN(-1)=3). PMID- 22093350 TI - Synthesis and characterisation of immunogens for the production of antibodies against small hydrophobic molecules with biosignature properties. AB - In the present study, five different classes of small hydrophobic molecular targets, atypical for antibody generation, were structurally modified in order to introduce suitable reactive functionalities and/or spacers which allow covalent coupling to a carrier protein resulting in a stable carrier-hapten complex. These targets were chosen to serve as markers of extant and/or extinct life in the context of the development of the Life Marker Chip (LMC), an antibody-based instrument, which is being developed by a UK-led international consortium for flight to Mars on board the joint ESA/NASA Mars exploration ExoMars mission. The hapten-protein conjugates were designed to be used as immunogens for antibody generation and immunoassay reagents in subsequent stages of the LMC development. The extent of protein modification due to covalent attachment of hapten was determined by two independent methods, i.e. trinitrobenzenesulfonic acid (TNBSA) titrations of remaining protein reactive groups and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of the resultant hapten protein conjugates. In a further quality validation step, the conjugates were presented to an animal's immune system and polyclonal antibody titres with moderate specificity were obtained. These results suggest that conjugates synthesized as described herein can successfully be used in the generation of antibodies targeting small hydrophobic molecules. PMID- 22093352 TI - Terbium hybrid particles with spherical shape as luminescent probe for detection of Cu2+ and Fe3+ in water. AB - A novel green emissive terbium inorganic-polymeric hybrid particle was designed and this material could detect cations in water. Polyvinyl alcohol as an amphiphilic surfactant rendered the powders dispersible in water with regular round shape (10-20 MUm). Interestingly, we noticed that not only Cu(2+) (detection limit 10(-4)M) but also Fe(3+) (detection limit 10(-4) M) can give rise to emission quenching to this target material in comparison with K(+), Na(+), Fe(2+), Mn(2+), Pd(2+), Cd(2+) and Co(2+) (10(-3) mol L(-1)). We regarded that the coordination interactions between ligand and metal ions resulted in these quenching processes. Additionally, it was found that the sensing material can be repeatedly used at least 5 cycles. More importantly, this novel material demonstrated higher thermal-stability in aqueous media than pure silica hybrid material. PMID- 22093351 TI - Selective recognition of monohydrogen phosphate by fluorescence enhancement of a new cerium complex. AB - Bis(8-hydroxy quinoline-5-solphonate) cerium(III) chloride (Ce(QS)(2)Cl) (L) was synthesized and then used as a novel fluorescent sensor for anion recognition. Preliminarily study showed that fluorescence of L enhanced selectively in the presence of HPO(4)(2-) ion. This enhancement is attributed to a 1:1 complex formation between L and HPO(4)(2-) anion. The association constant of 1:1 complex of L-HPO(4)(2-) was calculated as 3.0*10(6). Thus, L was utilized as a basis for a selective detection of HPO(4)(2-) anion in solution. The linear response range of the proposed fluorescent chemo-sensor covers a concentration range of HPO(4)(2 ) from 3.3*10(-7) to 5.0*10(-6) mol L(-1) with a detection limit of 2.5*10(-8) mol L(-1). L showed selective and sensitive fluorescence enhancement response toward HPO(4)(2-) ion in comparison with I(3)(-), NO(3)(-), CN(-), CO(3)(2-), Br( ), Cl(-), F(-), H(2)PO(4)(-) and SO(4)(2-) ions. It was probably attributed to the higher stability of the inorganic complex between HPO(4)(2-) ion and L. The method was successfully applied for analysis of phosphate ions in some fertilizers samples. PMID- 22093353 TI - Development of a highly sensitive and robust Cor a 9 specific enzyme-linked immunosorbent assay for the detection of hazelnut traces. AB - Allergy to tree nuts represents an acute health problem. Sensitized people can be inadvertently exposed to hidden allergens resulting from cross-contamination of foods. For this reason, reliable and highly sensitive analytical methods are needed to be developed for control and labeling of food ingredients and products. In the present paper we have proposed a new allergen specific sandwich-ELISA for hazelnut operated in optical and electrochemical modes. The ELISA was based on chicken egg yolk antibodies raised against a major hazelnut allergen, Cor a 9. The developed ELISA has a limit of detection in phosphate buffer of 4 ng mL(-1). No significant cross-reactivity with peanut, wheat or other food ingredients has been detected. Extracts of blank control cookies did not show any false positive response and the limit of detection in cookies was estimated to be 0.1 MUg of hazelnut protein per g of food (0.1 ppm). The ELISA protocol was successfully adapted to operate in electrochemical mode and it was applied for the detection of hazelnut traces in cookies. PMID- 22093354 TI - A simple, rapid and high-throughput fluorescence polarization immunoassay for simultaneous detection of organophosphorus pesticides in vegetable and environmental water samples. AB - A simple, rapid and high-throughput fluorescent polarization immunoassay (FPIA) for simultaneous determination of organophosphorus pesticides (OPs) using a broad specificity monoclonal antibody was developed. The effects of tracer structure, tracer concentration, antibody dilution, methanol content and matrix effect on FPIA performance were studied. The FPIA can detect 5 OPs simultaneously with a limit of detection below 10 ng mL(-1). The time required for the equilibrium of antibody-antigen interaction was less than 10 min. The recovery from spiked vegetable and environmental samples ranged from 71.3% to 126.8%, with the coefficient of variations ranging from 3.5% to 14.5%. The developed FPIA was applied to samples, followed by confirmation with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. The developed FPIA demonstrated good accuracy and reproducibility, and is suitable for rapid and high-throughput screening for OP contamination with high-efficiency and low cost. PMID- 22093355 TI - A colorimetric probe for online analysis of sulfide based on the red shifts of longitudinal surface plasmon resonance absorption resulting from the stripping of gold nanorods. AB - A gold nanorods (GNRs) nonaggregation-based colorimetric probe has been developed for the detection of S(2-) based on that the longitudinal surface plasmon resonance absorption wavelength (LPAW) of GNRs red shifts (Deltalambda) and the color of the solution distinctly changes on account of the faster stripping of GNRs along longitudinal axis than transverse axis in the process of GNRs reacting with S(2-) ions to form Au(2)S complexes on the GNRs surfaces. The GNRs probe exhibits highly sensitive and selective response toward S(2-) with a wide linear range from 10.0 to 10000.0 MUM. The proposed colorimetric probe can be used to visibly detect S(2-) in water samples on line in 15 min with the results agreeing well with those of the optical sensor, showing its great practicality. Moreover, the detection mechanism of the probe is also discussed. PMID- 22093356 TI - Synthesis in aqueous solution and characterisation of a new cobalt-doped ZnS quantum dot as a hybrid ratiometric chemosensor. AB - In this paper, cobalt (Co(2+))-doped (CoD) ZnS quantum dots (QDs) are synthesised in aqueous solution and characterised for the first time. L-Cysteine (L-Cys) ligands on the surface of CoD ZnS QDs can bind 2,4,6-trinitrotoluene (TNT) to form Meisenheimer complexes (MHCs) mainly through acid-base pairing interactions between TNT and L-Cys and the assistance of hydrogen bonding and electrostatic co interactions among L-Cys intermolecules. The aggregation of inter-dots induced by MHCs greatly influenced the light scattering property of the QDs in aqueous solution, and Rayleigh scattering (RS) enhancement at the defect-related emission wavelengths as well as its left side was observed with the excitation of CoD ZnS QDs by violet light. RS enhancement, combining with the quenching of the orange transition emission induced by TNT anions, resulted in a change in the ratiometric visualisation of the system being investigated. A novel CoD ZnS QD based hybrid ratiometric chemosensor has therefore been developed for simple and sensitive analysis of TNT in water. This ratiometric probe can assay down to 25 nM TNT in solution without interference from a matrix of real water sample and other nitroaromatic compounds. Because of the excellent electron-accepting ability and strong affinity of TNT to L-Cys on the surface of CoD ZnS QDs, the CoD photoluminescent nanomaterials reported here are well suited for detecting ultra-trace TNT and for distinguishing different nitro-compounds in aqueous solution. PMID- 22093357 TI - Sensitivity evaluation of rhodamine B hydrazide towards nitric oxide and its application for macrophage cells imaging. AB - A colorless and non-fluorescent rhodamine derivative, rhodamine B hydrazide (RH), is applied to detect nitric oxide and form fluorescent rhodamine B (RB). The reaction mechanism of RH with NO is proposed in this study. The probe shows good stability over a broad pH range (pH>4). Furthermore, fluorescence intensity of RH displays an excellent linearity to the NO concentration and the detection limit is as low as 20 nM. A 1000-fold fluorescence turn-on from a dark background was observed. Moreover, the selectivity study indicated that the fluorescence intensity increasing in the presence of NO was significantly higher than those of other reactive oxygen/nitrogen species. In exogenously generated NO detection study, clear intracellular red fluorescence was observed in the presence of S nitroso-N-acetyl-D,L-penicillamine (SNAP, a kind of NO releasing agent). In endogenously generated NO detection study, increasing incubation time of RH with lipopolysaccharied (LPS) pre-treated cells could obtain a highly fluorescent cell image. These cell imaging results demonstrated that RH can efficiently penetrate into Raw 264.7 cells and be used for detection of exogenously and endogenously generated nitric oxide. PMID- 22093358 TI - Development of a polymerase chain reaction and capillary gel electrophoresis method for the detection of chicken or turkey meat in heat-treated pork meat mixtures. AB - A polymerase chain reaction and capillary gel electrophoresis (PCR-CGE) method with ultraviolet (UV) or laser induced fluorescence detection (LIF) was established for the detection of chicken or turkey in heat-treated pork meat mixtures. Mitochondrial DNA samples extracted from heat treated meat were amplified with their corresponding specific primers yielding PCR products between 200 and 300 bp. LIF detection was superior than UV detection in terms of precision and sensitivity for the study of DNA fragments. The CGE-LIF method was highly reproducible and accurate for determining DNA fragment size. The PCR-CGE LIF was sensitive since a significant fluorescent signal was obtained at the minimum admixture level employed of 1% in meat mixtures. Thus, the PCR-CGE-LIF method established was useful for the detection of chicken or turkey in heat treated meat mixtures and may prove to be useful for the detection of poultry meat in pork processed products. PMID- 22093359 TI - Determination of triazine herbicides in environmental water samples by high performance liquid chromatography using graphene-coated magnetic nanoparticles as adsorbent. AB - In this paper, a graphene-based Fe(3)O(4) magnetic nanoparticles (G-Fe(3)O(4) MNPs) was used as the adsorbent for the magnetic solid-phase extraction of some triazine herbicides (atrazine, prometon, propazine and prometryn) in environmental water samples followed by high performance liquid chromatography diode array detection (HPLC-DAD). After the extraction, the adsorbent can be conveniently separated from the aqueous samples by an external magnet. The main factors influencing the extraction efficiency including the amount of the MNPs, the extraction time, the pH of sample solution, and desorption conditions were studied and optimized. Under the optimized experimental conditions, a good linearity was observed in the range of 0.1-50.0 ng mL(-1) for all the analytes, with the correlation coefficients (r) ranging from 0.9996 to 0.9999. The limits of detection of the method ranged between 0.025 and 0.040 ng mL(-1). Good reproducibility was obtained with the relative standard deviations below 5.2%. The developed method was applied to the analysis of the triazine herbicides in different water samples (lake, river and reservoir). The recoveries of the method were in the range between 89.0% and 96.2%. PMID- 22093360 TI - Variance decomposition of protein profiles from antibody arrays using a longitudinal twin model. AB - BACKGROUND: The advent of affinity-based proteomics technologies for global protein profiling provides the prospect of finding new molecular biomarkers for common, multifactorial disorders. The molecular phenotypes obtained from studies on such platforms are driven by multiple sources, including genetic, environmental, and experimental components. In characterizing the contribution of different sources of variation to the measured phenotypes, the aim is to facilitate the design and interpretation of future biomedical studies employing exploratory and multiplexed technologies. Thus, biometrical genetic modelling of twin or other family data can be used to decompose the variation underlying a phenotype into biological and experimental components. RESULTS: Using antibody suspension bead arrays and antibodies from the Human Protein Atlas, we study unfractionated serum from a longitudinal study on 154 twins. In this study, we provide a detailed description of how the variation in a molecular phenotype in terms of protein profile can be decomposed into familial i.e. genetic and common environmental; individual environmental, short-term biological and experimental components. The results show that across 69 antibodies analyzed in the study, the median proportion of the total variation explained by familial sources is 12% (IQR 1-22%), and the median proportion of the total variation attributable to experimental sources is 63% (IQR 53-72%). CONCLUSION: The variability analysis of antibody arrays highlights the importance to consider variability components and their relative contributions when designing and evaluating studies for biomarker discoveries with exploratory, high-throughput and multiplexed methods. PMID- 22093361 TI - Effect of thermal expansion mismatch on the Y-TZP/veneer interfacial adhesion determined by strain energy release rate. AB - PURPOSES: The aim of this study was to assess the effect of differences in the thermal expansion behaviour of veneering ceramics on the adhesion to Y-TZP, using a fracture mechanics approach. METHODS: Seven veneering ceramics (VM7, VM9, VM13, Lava Ceram, Zirox, Triceram, Allux) and one Y-TZP ceramic were investigated. Thermal expansion coefficients and glass transition temperatures were determined to calculate residual stresses (sigma(R), MPa) between core and veneer. Subsequently, the veneering ceramics were fired onto rectangular shaped zirconia specimens, ground flat and notched on the veneering porcelain side. Then specimens were loaded in a four-point bending test and load-displacement curves were recorded. The critical load to induce stable crack extension at the adhesion interface was evaluated to calculate the strain energy release rate (G, J/m(2)) for each system. RESULTS: Residual stresses ranged from -48.3+/-1.5MPa (VM7) to 36.1+/-4.8MPa (VM13) with significant differences between all groups (p<0.05). The strain energy release rate of the Y-TZP/veneer specimens ranged from 8.2+/ 1.7J/m(2) (Lava Ceram) to 17.1+/-2.8J/m(2) (VM9). Values for G could not be obtained with the VM7, Allux and VM13 specimens, due to spontaneous debonding or unstable crack growth. Except for Triceram and Zirox specimens, strain energy release rate was significantly different between all groups (p<0.05). CONCLUSION: Thermal residual stresses and strain energy release rates were correlated. Slight compressive stresses in the region of -20MPa were beneficial for the Y-TZP/veneer interfacial adhesion. Stresses higher or lower than this value exhibited decreased adhesion. PMID- 22093362 TI - Effect of vertical misfit on strain within screw-retained implant titanium and zirconia frameworks. AB - PURPOSE: To assess the implication of vertical misfit on strain within implant frameworks manufactured in titanium or zirconia. METHODS: A master model was fabricated by inserting a Branemark implant in left side of a mandibular model in the area of the first premolar and the first molar. This model was used to fabricate identical frameworks, five in titanium and five in zirconia. A single strain gauge was mounted on the occlusal surface of each framework to assess strain development as a result of framework fitting. In addition, the peak-to peak strain amplitude was measured for each framework to determine the strain pattern fluctuation. The vertical gap of the framework-implant interface was measured using a measuring microscope, when only one screw was tightened (1-screw test) and when both screws were tightened (2-screw test). The vertical fit of the frameworks was altered by adding one to three layers of 30 MUm steel shims on one of the implants. RESULTS: For all fitting conditions, measurable amount of strains were recorded, however, as the vertical misfit was introduced, linear increase in framework strain was detected. The titanium and zirconia frameworks exhibited similar strain activities. A direct relationship was observed between the framework strain and vertical gap. CONCLUSIONS: Framework misfit clearly influenced the framework strain magnitude and pattern. The framework material did not affect the framework strain for a similar level of misfit. PMID- 22093363 TI - Multiple Trypanosoma infections are common amongst Glossina species in the new farming areas of Rufiji district, Tanzania. AB - BACKGROUND: Tsetse flies and trypanosomiasis are among several factors that constrain livestock development in Tanzania. Over the years Rufiji District was excluded from livestock production owing to tsetse fly infestation, however, a few years ago there was an influx of livestock following evictions aimed at conserving the Usangu wetlands. METHODS: A study was conducted to determine the efficiency of available traps for catching tsetse flies, Glossina species infesting the area, their infection rates and Trypanosoma species circulating in the area. Trapping was conducted during the semi dry season for a total of 30 days (ten days each month) during the onset of the dry season of May - July 2009. Harvested flies after every 24 hours were dissected and examined under a light microscope for trypanosome infections and whole fly DNA was extracted from 82 flies and analyzed for trypanosomes by polymerase chain reaction (PCR) using different sets of primers. RESULTS: The proportions of total tsetse catches per trap were in the following decreasing order S3 (33%), H-Trap (27%), Pyramidal (19%), sticky panel (11%) and biconical trap (10%). Of the 1200 trapped flies, 75.6% were identified as Glossina pallidipes, 11.7% as G. brevipalpis, 9.6% as G. austeni and 3.0% G. morsitans morsitans. Dissections revealed the overall infection rate of 6.6% (13/197). Whole DNA was extracted from 82 tsetse flies and the prevalence of trypanosomes circulating in the area in descending order was 92.7% (76/82) for T. simiae; 70.7% (58/82) for T. brucei types; 48.8% (40/82) for the T. vivax types and 32.9% (27/82) for the T. congolense types as determined by PCR. All trypanosome types were found in all tsetse species analysed except for the T. congolense types, which were absent in G. m. morsitans. None of the T. brucei positive samples contained human infective trypanosomes by SRA - PCR test CONCLUSION: All tsetse species found in Rufiji are biologically important in the transmission of animal trypanosomiasis and the absence of T. congolense in G. m. morsitans could be a matter of chance only. Therefore, plans for control should consider all tsetse species. PMID- 22093364 TI - Identification and characterization of novel spliced variants of PRMT2 in breast carcinoma. AB - Protein N-arginine methyltransferases (PRMTs) participate in a number of cellular processes, including cell growth, nuclear/cytoplasmic protein shuttling, differentiation, RNA splicing and post-transcriptional regulation. PRMT2 (also known as HRMT1L1) is clearly involved in lung function, the inflammatory response, apoptosis promotion, Wnt signaling and leptin signaling regulation through different mechanisms. In this study, we report the molecular and cell biological characterization of three novel PRMT2 splice variants isolated from breast cancer cells and referred to as PRMT2alpha, PRMT2beta and PRMT2gamma. Compared with the wild-type PRMT2, these variants lack different motifs and therefore generate distinct C-terminal domains. Confocal microscopy scanning revealed a distinct intracellular localization of PRMT2 variants, suggesting that the alternatively spliced C-terminus of PRMT2 can directly influence its subcellular localization. Our findings reveal that these variants are capable of binding to estrogen receptor alpha (ERalpha) both in vitro and in vivo, and the N terminal regions of these variants contribute to ERalpha-PRMT2 interactions. Furthermore, these variants were proved to be able to enhance ERalpha-mediated transactivation activity. Luciferase reporter assays showed that PRMT2s could modulate promoter activities of the ERalpha-targeted genes of Snail and E cadherin. In addition, PRMT2 silencing could enhance 17beta-estradiol-induced proliferation by regulating E2F1 expression and E2F1-responsive genes in ERalpha positive breast cancer cells. Real-time PCR and immunohistochemistry showed that overall PRMT2 expression was upregulated in breast cancer tissues and significantly associated with ERalpha positivity status both in breast cancer cell lines and breast cancer tissues. We speculate that PRMT2 and its splice variants may directly modulate ERalpha signaling and play a role in the progression of breast cancer. PMID- 22093365 TI - Diagnosis and demarcation of skin malignancy using elastic light single scattering spectroscopy: a pilot study. AB - BACKGROUND: Elastic light single-scattering spectroscopy (ELSSS) is a noninvasive and real-time technique that has been used to differentiate tumors from surrounding nontumor tissue in animal models and humans. OBJECTIVE: To investigate potential application of ELSSS as an adjunctive tool for noninvasive, in vivo, real-time differentiation of malignant and benign skin lesions and to detect positive surgical margins of excised biopsy samples. METHODS: In vivo spectroscopic measurements were performed on 28 lesions in 23 patients. The distribution of the lesions was as follows: nine basal cell carcinoma (BCC), four melanoma, two squamous cell carcinoma (SCC), and 13 benign lesions. Intraoperative margin assessments were performed on the 28 biopsy samples using ELSSS. RESULTS: The sign of the spectral slopes was positive for benign and negative for malignant tissues. It was used as a discrimination parameter between malignant and benign lesions with a sensitivity and specificity of 87% and 85%, respectively. Sensitivity and specificity of the system in detecting positive surgical margins on 14 excised biopsy samples were 80% and 90%, respectively. CONCLUSION: ELSSS has the potential for use as an adjunctive tool to reduce the number of negative biopsies and to detect positive surgical margins in real time. PMID- 22093367 TI - Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. AB - Folate plays a critical role in the prevention of uracil incorporation into DNA and hypomethylation of DNA. This activity is compromised when vitamin B12 concentration is low because methionine synthase activity is reduced, lowering the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA methylation and cause folate to become unavailable for the conversion of dUMP to dTMP. The most plausible explanation for the chromosome-breaking effect of low folate is excessive uracil misincorporation into DNA, a mutagenic lesion that leads to strand breaks in DNA during repair. Both in vitro and in vivo studies with human cells clearly show that folate deficiency causes expression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micronucleus formation, DNA hypomethylation and mitochondrial DNA deletions. In vivo studies show that folate and/or vitamin B12 deficiency and elevated plasma homocysteine (a metabolic indicator of folate deficiency) are significantly correlated with increased micronucleus formation and reduced telomere length respectively. In vitro experiments indicate that genomic instability in human cells is minimised when folic acid concentration in culture medium is greater than 100nmol/L. Intervention studies in humans show (a) that DNA hypomethylation, chromosome breaks, uracil incorporation and micronucleus formation are minimised when red cell folate concentration is greater than 700nmol/L and (b) micronucleus formation is minimised when plasma concentration of vitamin B12 is greater than 300pmol/L and plasma homocysteine is less than 7.5MUmol/L. These concentrations are achievable at intake levels at or above current recommended dietary intakes of folate (i.e. >400MUg/day) and vitamin B12 (i.e. >2MUg/day) depending on an individual's capacity to absorb and metabolise these vitamins which may vary due to genetic and epigenetic differences. PMID- 22093368 TI - False-positive Aspergillus galactomannan assay in solid organ transplant recipients with histoplasmosis. AB - Post-transplantation histoplasmosis may be acquired via inhalation, may result from endogenous reactivation, or may be derived from the allograft. The Histoplasma and Aspergillus enzyme-linked immunoassays are increasingly being relied upon for rapid diagnosis of fungal infections, especially in immunocompromised patients. We describe 4 cases of solid organ transplant recipients who had histoplasmosis and a falsely positive Aspergillus galactomannan (GM) obtained from the serum or bronchoalveolar lavage (BAL) fluid. We also report our experience, testing for Histoplasma antigen (Ag) in specimens positive for Aspergillus GM. From January 2007 through December 2010, of 2432 unique patients who had positive Aspergillus GM tests, 514 (21%) were tested for Histoplasma Ag, and 27 were found to be positive. Most specimens that tested positive for both Aspergillus and Histoplasma were obtained by BAL. False positive tests for Aspergillus GM can occur in immunosuppressed patients who have histoplasmosis, and may obscure the correct diagnosis. PMID- 22093369 TI - Surface properties of bacteria sensitive and resistant to the class IIa carnobacteriocin Cbn BM1. AB - AIMS: Class IIa bacteriocins are small antimicrobial peptides synthesized by lactic acid bacteria. The proposed mechanisms of action for class IIa bacteriocins suggest that the physicochemical properties of the target bacterial surface govern the bacteriocin antimicrobial activity. The aim of this study is to decipher the relationship between both sensitivity and resistance to a class IIa bacteriocin, carnobacteriocin BM1 and physicochemical surface properties of bacteria. METHODS AND RESULTS: The study was performed on 18 strains by a microbial adhesion to solvents process and with electrophoretic mobility measurements considering bacteria as soft particles. A large variation in bacterial surface properties is observed among the bacterial populations. Electro hydrodynamic parameters values appear to be more homogeneous for sensitive strains than for the resistant ones, which can exhibit more extreme values. CONCLUSIONS: Physicochemical surface properties of 18 strains determined show large variations between the strains. However, no direct link between these surface properties and the resistant/sensitive phenotypes of the strains can be stated. SIGNIFICANCE AND IMPACT OF THE STUDY: The surface physicochemical properties tested have a low predictive power to discriminate sensitive or resistant strains when determined at the bacterial population scale. PMID- 22093366 TI - It all comes together at the ends: telomerase structure, function, and biogenesis. AB - Telomerase is a reverse transcriptase specialized in the addition of telomeric DNA repeats onto the ends of chromosomes. Telomere extension offsets the loss of telomeric repeats from the failure of DNA polymerases to fully replicate linear chromosome ends. Telomerase functions as a ribonucleoprotein, requiring an integral telomerase RNA (TR) component, in addition to the catalytic telomerase reverse transcriptase (TERT). Extensive studies have identified numerous structural and functional features within the TR and TERT essential for activity. A number of accessory proteins have also been identified with various functions in enzyme biogenesis, localization, and regulation. Understanding the molecular mechanism of telomerase function has significance for the development of therapies for telomere-mediated disorders and cancer. Here we review telomerase structural and functional features, and the techniques for assessing telomerase dysfunction. PMID- 22093370 TI - Biofortification for combating 'hidden hunger' for iron. AB - Micronutrient deficiencies are responsible for so-called 'hidden undernutrition'. In particular, iron (Fe) deficiency adversely affects growth, immune function and can cause anaemia. However, supplementation of iron can exacerbate infectious diseases and current policies of iron therapy carefully evaluate the risks and benefits of these interventions. Here we review the approaches of biofortification of valuable crops for reducing 'hidden undernutrition' of iron in the light of the latest nutritional and medical advances. The increase of iron and prebiotics in edible parts of plants is expected to improve health, whereas the reduction of phytic acid concentration, in crops valuable for human diet, might be less beneficial for the developed countries, or for the developing countries exposed to endemic infections. PMID- 22093371 TI - A structural phylogenetic map for chloroplast photosynthesis. AB - Chloroplasts are cytoplasmic organelles and the sites of photosynthesis in eukaryotic cells. Advances in structural biology and comparative genomics allow us to identify individual components of the photosynthetic apparatus precisely with respect to the subcellular location of their genes. Here we present outline maps of four energy-transducing thylakoid membranes. The maps for land plants and red and green algae distinguish protein subunits encoded in the nucleus from those encoded in the chloroplast. We find no defining structural feature that is common to all chloroplast gene products. Instead, conserved patterns of gene location are consistent with photosynthetic redox chemistry exerting gene regulatory control over its own rate-limiting steps. Chloroplast DNA carries genes whose expression is placed under this control. PMID- 22093372 TI - [Corneal sensitivity in patients treated medically for glaucoma or ocular hypertension]. AB - PURPOSE: To evaluate the corneal sensitivity in patients treated with intraocular pressure (IOP)-lowering medications. INTRODUCTION: Chronic administration of anti glaucoma drops is associated with numerous tissue changes on the ocular surface. The purpose of this study was to investigate the effect of these medications and their preservative, benzalkonium chloride (BAK), on corneal sensitivity. PATIENTS AND METHODS: Thirty-nine patients treated for glaucoma or ocular hypertension (OHT) and nine untreated patients were included in this study. Treated patients were divided into three groups according to the daily number of preserved eyedrops (0, 1 and >=2). Corneal sensitivity was assessed using the Cochet-Bonnet esthesiometer. All patients underwent a complete examination of the ocular surface including Schirmer testing, tear film breakup time (BUT) and corneal and conjunctival fluorescein staining. The Ocular Surface Disease Index (OSDI) questionnaire was used to evaluate symptoms. RESULTS: Corneal sensitivity was 58.8+/-2.8mm, 56.2+/-5.2mm, 50.3+/-12.5mm and 44.3+/-13.6mm in untreated patients, in patients treated with none, one and two or more instillations of preserved eyedrops, respectively. Corneal sensitivity in patients treated with preserved eyedrops was significantly lower as compared to untreated patients (P<0.001) and patients treated with preservative-free eyedrops (P=0.012). Corneal sensitivity of patients treated with intraocular pressure-lowering medications was negatively correlated to the number of instillations of preserved eyedrops (r=-0.390 ; P<0.001) as well as to the duration of treatment (R=-0.357 ; P=0.001). BUT and fluorescein staining were significantly altered in treated patients compared to the untreated control group ; however, no significant difference was observed between the treated groups. There was no significant difference for OSDI or Schirmer testing between the various groups. CONCLUSION: Chronic administration of BAK-containing anti-glaucoma eyedrops appears to alter corneal sensitivity. These results could explain the absence of correlation between clinical signs and symptoms sometimes observed in patients treated for glaucoma or OHT. PMID- 22093374 TI - Eudragit E100 surface activity and lipid interactions. AB - Eudragit E100 (E100) is a cationic methacrylate polymer that interacts with viral and cell membranes. We studied the effect of pH, ionic strength and the presence of lipid monolayers on the surface activity of the polymer. E100 forms stable monolayers at the air-water interface, either by spreading or when added into the subphase. This behavior is highly influenced by the pH and saline concentration of the subphase. At pH 5 or higher, the adsorption of the polymer to the air water interface begins immediately after its injection into the subphase, while at pH below 5 E100 remains in the subphase with a particularly slow adsorption to the interface. In addition, low ionic strength (10 mM) in the subphase results in a fast adsorption of the polymer to the interface, even at pH under 5. On the other hand, in the presence of non-ionic (cholesterol) or anionic (monosialoganglioside) lipid monolayers, E100 shows a fast adsorption to the interface, [comma] reaching surface pressures of 25 and 36 mN m(-1), respectively. However, E100 barely interacts with monolayers of a zwitterionic lipid (hydrogenated soy lecithin) with a cut-off pressure of 11 mN m(-1). The interaction of E100 with GM1 micelles in the subphase reduces its surface activity. Altogether these results show that E100 can effectively penetrate into model membranes and that its amphipathic character is largely dependent on the chemical composition of the aqueous environment and the lipid composition of the membrane. PMID- 22093373 TI - Strong serological responses and HIV RNA increase following AS03-adjuvanted pandemic immunization in HIV-infected patients. AB - INTRODUCTION: We aimed to determine the antibody responses and effect on viral load of the AS03-adjuvanted pandemic H1N1 vaccine in HIV-infected patients. METHOD: A total of 121 HIV-infected patients and 138 healthy subjects were enrolled in a prospective, open-label study. Healthy subjects received one dose and HIV-infected patients two doses of the AS03-adjuvanted split influenza A/09/H1N1 vaccine (Pandemrix(r); GlaxoSmithKline, Brentford, United Kingdom.) at an interval of 3-4 weeks. The study was extended in 2010/2011 for 66 patients. Geometric mean titres (GMTs), seroprotection rates (post-vaccination titre >= 1:40) and HIV-1 RNA levels were measured before and 4 weeks after immunization. RESULTS: After two immunizations, the seroprotection rate (94.2 vs. 87%, respectively) and GMT (376 vs. 340, respectively) in HIV-infected patients were as high as in healthy subjects after one dose, regardless of CD4 cell count. Four weeks after immunization, HIV RNA was detected in plasma samples from 40 of 68 (58.0%) previously aviraemic patients [median 152 HIV-1 RNA copies/mL; interquartile range (IQR) 87-509 copies/mL]. Subsequent measures indicated that HIV RNA levels had again declined to <20 copies/mL in most patients (27 of 34; 79.4%). Following (nonadjuvanted) influenza immunization in 2010/2011, HIV RNA levels only slightly increased (median final level 28 copies/mL) in three of 66 (4.5%) previously aviraemic patients, including two of 25 (8%) patients in whom an increase had been elicited by AS03-adjuvanted vaccine the year before. CONCLUSION: Most HIV-infected patients developed seroprotection after two doses of AS03-adjuvanted pandemic vaccine. A transient effect on HIV RNA levels was observed in previously aviraemic patients. A booster dose of the nonadjuvanted influenza vaccine containing the A/09/H1N1 strain the following year did not reproduce this finding, indicating a non-antigen-specific adjuvant effect. PMID- 22093375 TI - Adenoid cystic carcinoma of parotid gland treated with surgery and radiotherapy: long-term outcomes, QoL assessment and review of the literature. AB - To assess outcomes, toxicity and quality-of-life (QoL) of patients with parotid gland adenoid cystic carcinoma (PGACC) treated by surgery and postoperative radiotherapy. Between 1995 and 2010, 46 patients with PGACC were treated with parotidectomy+/-neck dissection followed by radiotherapy. Endpoints were loco regional control (LRC), distant metastasis-free (DMFS), disease-free (DFS), cause specific (CSS), and overall survival (OS), late toxicity, and QoL. After a median follow-up of 58 months (range 4-171), the 5-year Kaplan-Meier estimates of LRC, DMFS, DFS, CSS, and OS were 88%, 78%, 75%, 80%, and 67%, respectively and the 8 year rates were 88%, 75%, 72%, 77%, and 64%, respectively. On multivariate analysis, T-stage, N-stage, tumor grade, and perineural invasion correlate significantly with DMFS and DFS. The overall 5-year cumulative incidence of grade >=2 late toxicity was 9%. QoL-scores deteriorate during and shortly after treatment but returned in all scales to almost baseline levels within 6 months. Excellent LRC rates were achieved in patients with PGACC treated by surgery and postoperative radiotherapy with low rate of late side-effects and preservation of good QoL. Despite the effective local therapy, 9 of 46 patients (20%) failed distantly. Because effective treatment strategies for this problem are lacking, prospective trials are needed to determine the role of adjuvant systemic or targeted therapy in patients at high risk of DM. PMID- 22093376 TI - Trends and inequalities in laryngeal cancer survival in men and women: England and Wales 1991-2006. AB - Laryngeal cancer in men is a relatively common malignancy, with a marked socioeconomic gradient in survival between affluent and deprived patients. Cancer of the larynx in women is rare. Survival tends to lower than for men, and little is known about the association between deprivation and survival in women with laryngeal cancer. This paper explores the trends and socio-economic inequalities in laryngeal cancer survival in women, with comparison to men. We examined relative survival among men and women diagnosed with laryngeal cancer in England and Wales during 1991-2006, followed up to 31 December 2007. We estimated the difference in survival between the most deprived and most affluent groups (the 'deprivation gap') at one and five years after diagnosis, for each sex, anatomical subsite and calendar period. Five year survival for all laryngeal cancers combined was up to 8% lower in women than in men. This difference is only partially explained by the differential distribution of anatomical subsites in men and women. Disparities in survival between men and women were also present within specific subsites. In contrast to men, there was little evidence of a consistent deprivation gap in survival for women at any of the anatomical subsites. The stark socioeconomic inequalities in laryngeal cancer survival in men do not appear to be replicated in women. The origins of the socio-economic inequalities in survival among men, and the disparities in survival between men and women at specific tumour subsites remains unclear. PMID- 22093377 TI - Metabolic effects of sleeve gastrectomy in female rat model of diet-induced obesity. AB - BACKGROUND: Although women disproportionately undergo bariatric surgery, the rodent models investigating the mechanisms of bariatric surgery have been limited to males. Female rodent models can also potentially allow us to understand the effects of surgical intervention on future generations of offspring. Sleeve gastrectomy is an attractive weight loss procedure for reproductive-age female patients because it avoids the malabsorption associated with intestinal bypass. We sought to evaluate the effect of sleeve gastrectomy on young female rats with diet-induced obesity at the University of California, Los Angeles, David Geffen School of Medicine. METHODS: Sprague-Dawley female rats were fed a 60% high-fat diet. At 12 weeks of age, the rats underwent either sleeve gastrectomy or sham surgery. The rats were killed 4 weeks after surgery. A chemistry panel was performed, and the serum adipokines and gut hormones were assayed. The homeostasis model assessment score was calculated. The liver histologic findings were graded for steatosis. The 2-sample t test was used to compare the results between the 2 groups. RESULTS: Sleeve gastrectomy was associated with significant weight loss (5% +/- 6% versus -4% +/- 6%; P < .001), lower leptin levels (1.3 +/- 1.2 versus 3.5 +/- 2.3 ng/mL; P < .01), and higher adiponectin levels (.43 +/- .19 versus .17 +/- .14 ng/mL; P < .004) compared with the sham-operated rats. No significant differences were found in the fasting ghrelin levels. Furthermore, we did not observe evidence of insulin resistance or steatohepatitis after 11 weeks of high-fat diet. Despite these limitations, additional gender-specific studies are warranted given that most bariatric surgeries are performed in women. CONCLUSION: Sleeve gastrectomy appears to result in weight loss and improvements in adiponectin and leptin by way of mechanisms independent of ghrelin levels in a female model of diet-induced obesity. PMID- 22093378 TI - Laparoscopic bariatric surgery for those with body mass index of 70-125 kg/m2. AB - BACKGROUND: Data on laparoscopic bariatric surgery in the extremely obese are limited. Technical difficulties, in addition to the patients' severe weight related co-morbidities, can compromise the safety of bariatric surgery in these patients. Our objectives were to assess the safety and feasibility of laparoscopic bariatric surgery in extremely obese patients and to compare the outcomes of different surgical approaches at a bariatric surgery center of excellence in an academic medical center. METHODS: We reviewed our prospectively collected database and identified all patients with a body mass index (BMI) of >= 70 kg/m(2) who had undergone bariatric surgery. The data on patient demographics, baseline characteristics, and outcomes of bariatric surgery were retrieved. RESULTS: A total of 49 patients with a mean BMI of 80.7 kg/m(2) (range 70-125) underwent 61 bariatric procedures. Of the 49 patients, 26 underwent sleeve gastrectomy, 11 gastric bypass, and 12 underwent a 2-stage procedure (sleeve gastrectomy followed by gastric bypass). At a mean follow-up of 17.4 months, the average BMI had decreased to 60.9 kg/m(2) (36% excess weight loss). Overall, the patients who underwent a 2-stage procedure achieved greater percentage of excess weight loss (54.5%) than did those who underwent either single-stage sleeve gastrectomy or gastric bypass (25.4%, P = .002 and 43.8%, P = .519, respectively). Of the 61 cases, 60 (98.4%) were completed laparoscopically. The early complication rate was 16.4% overall; most were minor complications. The late complication rate was 14.8%. A single late mortality occurred in this series. CONCLUSION: Laparoscopic bariatric surgery can be performed safely on patients with a BMI of >= 70 kg/m(2). A staged approach might offer better weight loss results. PMID- 22093379 TI - Body weight at developmental age in siblings born to mothers before and after surgically induced weight loss. AB - BACKGROUND: To gain insight into the role of epigenetic factors in determining body weight in adolescence, we studied the body weight of siblings born to the same mother before and after biliopancreatic diversion (BPD) for obesity. The study was performed in a university hospital during a 20-year period. METHODS: The siblings born before and after BPD were retrospectively rated by their mother as normal, overweight, or obese at 1, 6, and 12 years. RESULTS: At 1 and 6 years, the body weight was rated as similar in the subsets. However, at 12 years of age, a greater percentage of those born before BPD were considered overweight (42% versus 33%) and obese (22% versus 3%; P <.009) than their counterparts born after BPD. Considering only the subjects aged 21-25 years at the study period, the body weight and body mass index in subjects born before BPD were greater (P <.02 and P <.012, respectively) than in those born after BPD (79.5 +/- 16.5 kg versus 66.7 +/- 11.8 kg, and 27.5 +/- 3.9 kg/m(2) versus 23.4 +/- 3.7 kg/m(2), respectively). CONCLUSION: The results of the present study, in which the influences of the genetic pattern and environmental and educational factors were minimized, show that adolescents born to post-BPD mothers weigh less than their siblings born to the same mother before BPD when she was still obese. An insulin-resistant milieu during pregnancy could account for the greater body weight later in adolescence. PMID- 22093380 TI - Restoration of glycemic control in patients with type 2 diabetes mellitus after bariatric surgery is associated with reduction in microparticles. AB - BACKGROUND: Microparticles bud from cellular elements during inflammation and are associated with the vascular dysfunction related to type 2 diabetes mellitus. Although weight loss is known to reduce inflammation, the metabolic effects of bariatric surgery on microparticle concentration and composition are not known. Our objectives were to determine the effect of bariatric surgery on the microparticle concentration and to correlate these changes with clinical parameters in a multispecialty group practice. METHODS: We studied 14 obese subjects with type 2 diabetes mellitus 2 weeks before and 1 and 12 months after bariatric surgery. Of the 14 patients, 9 underwent Roux-en-Y gastric bypass and 5 gastric restrictive surgery. RESULTS: At 1 month after surgery, the body mass index had decreased by ~10%, glycemic control had improved dramatically (P < .01), and a >60% reduction in endothelial and platelet microparticles and C reactive protein levels (P < .05) had occurred. The tissue factor microparticles had decreased by 40% (P = .1). At 12 months after surgery, the body mass index had decreased by ~20%, glycemic control was maintained (P < .01), and a >50% reduction in monocyte microparticles compared with before surgery was found. The reduction in monocyte microparticles 1 month after surgery was strongly associated with the reduction in hemoglobin A1c (P < .05). The reduction in monocyte microparticles 12 months after surgery correlated strongly with the reduction in body mass index (P < .05). CONCLUSION: The reduction in microparticles after bariatric surgery in patients with type 2 diabetes mellitus reflects an attenuation of inflammation, and this mechanism might contribute to normalization of glycemic control. PMID- 22093382 TI - Development of a quantitative donor risk index to predict short-term mortality in orthotopic heart transplantation. AB - BACKGROUND: No standard index based on donor factors exists for predicting mortality after orthotopic heart transplantation (OHT). We utilized United Network for Organ Sharing (UNOS) data to develop a quantitative donor risk score for OHT. METHODS: We examined a prospectively collected open cohort of 22,252 patients who underwent primary OHT (1996 to 2007). Of the 284 donor-specific variables, those associated with 1-year (year) mortality (exploratory p-value < 0.2) were incorporated into a multivariate (MV) logistic regression model. The final model contained donor factors that improved the explanatory power (by pseudo-R2, area under the curve and likelihood ratio test). A quantitative donor risk score was created using odds ratios (ORs) from the final model. For external validity, a cross-validation strategy was employed whereby the score was generated using a randomly generated subset of cases (n = 17,788) and then independently validated on the remaining patients (n = 4,464). RESULTS: A 15 point scoring system incorporated 4 variables: ischemic time; donor age; race mismatching; and blood urea nitrogen (BUN)/creatinine ratio. Derivation and validation cohort scores ranged from 1 to 15 and 1 to 12, respectively (mean 4.0 +/- 2.1 for each). Each increase of 1 point increased the risk of 1-year death by 9% (OR = 0.09 [1.07 to 0.12]) in the derivation cohort and 13% (OR = 0.13 [1.08 to 0.18]) in the validation cohort (each p < 0.001). The odds of 1-year mortality by increments of 3 points were: 0 to 2 points (reference); 3 to 5 points (OR = 0.25 [1.12 to 0.40], p < 0.001); 6 to 8 pts (OR = 0.77 [1.56 to 2.02], p < 0.001); and 9 to 15 points (OR = 1.92 [1.54 to 2.39], p < 0.001). Donor risk score was predictive for 30-day mortality (OR = 0.11 [1.08 to 0.14], p < 0.001) and 5-year cumulative mortality (OR = 0.11 [1.09 to 0.13], p < 0.001). CONCLUSIONS: We present a novel donor risk index for OHT predicting short- and long-term mortality. This donor risk score may prove valuable for donor heart allocation and prognosis after OHT. PMID- 22093381 TI - Pro-inflammatory effector Th cells transmigrate through anti-inflammatory environments into the murine fetus. AB - The presence of maternal DNA or even maternal cells within the offspring (microchimerism) has been reported for many fetal tissues, including the liver, heart, and spleen. Microchimerism is believed to be involved in the pathogenesis of autoimmune diseases; however, the cellular origin of this phenomenon remains unknown. Here, we determined whether differentiated T lymphocytes could transmigrate through the immunosuppressive environment of the placenta to reach the fetus. In vitro-differentiated effector/memory Th1 and Th17 cells from OVA323 339-specific TCR(tg) T cells of OT-II mice were adoptively transferred (i.v.) into the tail veins of pregnant Ly5.1 mice at d15 and d19 of gestation. Mice were then sacrificed 40 h after adoptive cell transfer. Using radioactive labeling of T cells with sodium chromate [Cr51] prior to adoptive transfer, we observed that homing of pro-inflammatory Th cells was equally efficient in both pregnant and non-pregnant mice. Transmigration of Th1- and Th17-like cells through the highly immunosuppressive environment of the placenta into the fetus was significantly enhanced in experimental mice compared to control mice (P < 0.0001). In addition, a substantial amount of effector Th cells accumulated in the placenta. Finally, we found that treatment with Pertussis Toxin resulted in a 3-fold increase in the transmigration of effector Th17 cells into the fetus (P < 0.0001). When pro inflammatory Th1-or Th17-like cells were injected into syngeneic mothers, almost all of the fetuses analyzed exhibited radioactivity, suggesting that transmigration of effector T cells occurs frequently. Our results suggest the possibility of novel roles for these maternal effector cells in the pathogenesis or reduction of disease. PMID- 22093383 TI - Low diversity and low frequency of participation in leisure activities compromise working memory efficiency in young adults. AB - People perform leisure activities (LA) every day; pursuits that entail applying cognitive, physical and social abilities. As in old age, doing LA during early and middle adulthood is related to a reduced risk of dementias, probably by generating a cognitive reserve. As it is possible that a relation between doing LA and working memory (WM) efficiency exists in young adults, we assessed whether the diversity and frequency of LA are related to WM efficiency in this population. Ninety-three healthy young subjects solved the n-back task at two levels of difficulty (2, 3), and answered an LA questionnaire on the activities in which they had participated in the month prior to the experiment. Subjects were classified separately on their scores for (1) diversity (high/low) and (2) frequency (high/low) in order to test the relation between each variable and WM efficiency. Though no differences were found, a subsequent analysis of the average of diversity and frequency ratios of LA performance taken together-the diversity/frequency index-showed that low diversity plus low frequency was significantly associated with reduced WM efficiency at this age; results that suggest that frequent participation in diverse LA during youth is related to WM efficiency. PMID- 22093384 TI - Evidence, patient preferences and patient-centred care. PMID- 22093385 TI - Effectiveness of strategies for the management and/or prevention of hypothermia within the adult perioperative environment. AB - BACKGROUND: Inadvertent hypothermia is common in patients undergoing surgical procedures with a reported prevalence of perioperative hypothermia ranging from 50% to 90%. Hypothermia within the perioperative environment may have many undesired physiological effects that are associated with postoperative morbidity. There are different options for treating and/or preventing hypothermia within the adult perioperative environment, which include active and passive warming methods. This systematic review was undertaken to provide comprehensive evidence on the most effective strategies for prevention and management of inadvertent hypothermia in the perioperative environment. OBJECTIVE: The objective of this review was to identify the most effective methods for the treatment and/or preventions of hypothermia in intraoperative or postoperative patients. INCLUSION CRITERIA: Adult patients >= 18 years of age, who underwent any type of surgery were included in this review. Types of interventions included were any type of linen or cover, aluminium foil wraps, forced-air warming devices, radiant warming devices and fluid warming devices. This review considered all identified prospective studies that used a clearly described process for randomisation, and/or included a control group. The primary outcome of interest was change in core body temperature. REVIEW METHODS: Two independent reviewers assessed methodological validity of papers selected for retrieval and any disagreements were resolved through discussion. RESULTS: Nineteen studies with a combined 1451 patients who underwent different surgical procedures were included in this review. Meta-analysis was not possible. Forced-air warming in pregnant women scheduled for caesarean delivery under regional anaesthesia prevented maternal and foetal hypothermia. Intravenous and irrigating fluids warmed (38-40 degrees C) to a temperature higher than that of room temperature by different fluid warming devices (both dry and water heated) proved significantly beneficial to patients in terms of stable haemodynamic variables, and higher core temperature at the end of the surgery. Water garment warmer was significantly (P < 0.05) effective than forced-air warming in maintaining intraoperative normothermia in orthotopic liver transplantation patients. Extra warming with forced air compared to routine thermal care was effective in reducing the incidence of surgical wound infections and postoperative cardiac complications. Passive warming with reflective heating blankets or elastic bandages wrapped around the legs tightly were found to be ineffective in reducing the incidence or magnitude of hypothermia. CONCLUSION: There are significant benefits associated with forced air warming. Evidence supports commencement of active warming preoperatively and monitoring it throughout the intraoperative period. Single strategies such as forced-air warming were more effective than passive warming; however, combined strategies, including preoperative commencement, use of warmed fluids plus forced air warming as other active strategies were more effective in vulnerable groups (age or durations of surgeries). PMID- 22093386 TI - Effect of educational components and strategies associated with insulin pump therapy: a systematic review. AB - OBJECTIVES: The objectives of this review were to establish the effectiveness of approaches to the provision of education for adults with type 1 diabetes using or initiating insulin pump therapy (IPT), and identify the best available evidence on the association between intervals and duration of follow up and the stated outcome criteria. INCLUSION CRITERIA: This review considered all studies and papers that involved adults (aged 16 years or over) with type 1 diabetes using IPT as their primary form of therapy who participated in education or training, with no restrictions placed on gender or comorbidities. All forms of education, including resources utilised during education were included in the review. SEARCH STRATEGY: The search strategy sought to find both published and unpublished studies and papers written in the English language. An initial limited search of MEDLINE and CINAHL databases was undertaken to identify optimal search terms. A second search using all identified key words and index terms was then undertaken based on key words specific to each database across all included databases from 1998 to February 2008. Thirdly, the reference lists of all identified reports and articles were searched for additional studies. METHODOLOGICAL QUALITY: Two independent reviewers assessed the methodological quality of retrieved papers using the corresponding checklist from the System for the Unified Management, Assessment and Review of Information (SUMARI) package. RESULTS: A total of 142 studies were identified as potentially relevant to the review question in the first and second steps of the literature search. Based on the title and abstract, 24 papers that were relevant to the review topic were retrieved for evaluation of methodological quality. Following this stage, 20 papers were excluded. Whilst searching the reference lists of the selected studies (n = 4), one paper met the inclusion criteria. Therefore, a total of five descriptive studies were included in the review. The included papers reported a variety of educational methods and different outcome measures. CONCLUSION: In general, it is difficult to draw a strong conclusion regarding the effectiveness of components and strategies associated with IPT because of a lack of high-quality comparative studies, small sample sizes and a variability of reported methods in the included studies. However, included descriptive studies explored a range of issues related to the effectiveness of IPT therapy, and the educative requirements of patients. It is clear that type 1 diabetes patients initiating and utilising IPT need a comprehensive range of advice, education and training. The mixture of group and individual teaching, multidisciplinary teams as educators, educational materials, long-term training with multiple sessions and a variety of educational contents may all be effective for delivering IPT education and training. PMID- 22093387 TI - A comprehensive systematic review of visitation models in adult critical care units within the context of patient- and family-centred care. AB - AIM: The aim of this review was to appraise and synthesise the best available evidence on visitation models used in adult intensive care units in acute care hospitals and to explicate their congruence with the core concepts of patient- and family-centred care (PFCC). METHODS: The review considered both quantitative and qualitative studies on visitation models developed within the PFCC model in adult intensive care units in acute care hospitals. The search strategy sought published and unpublished research papers limited to English for the years 1988 through 2009. An initial search of the Joanna Briggs Institute for Evidence-Based Nursing and Midwifery, the Cochrane Library, and PubMed's Clinical Inquiry/Find Systematic Review database was conducted, followed by an analysis of key words contained in the title, abstract and index terms. Following this, an extensive three-stage search was conducted using PubMed, CINAHL, HealthStar, ScienceDirect, Dissertation Abstracts International, DARE, PsycINFO, BioMedCentral, TRIP, Pre CINAHL, PsycARTICLES, Psychology and Behavioural Sciences Collection, ISI Current Contents, Science.gov, Web of Science/Web of Knowledge, Scirus.com website. Included was a hand search of reference lists of identified papers to capture all pertinent material as well as a search of relevant worldwide websites and search engines, such as Google Scholar and the Virginia Henderson Library of Sigma Theta Tau International. Each paper was assessed independently by two reviewers for methodological quality prior to inclusion in the review using the appropriate critical appraisal instrument. RESULTS: Findings from the qualitative studies were extracted and a synthesis conducted using the QARI (Qualitative Assessment and Review Instrument) software developed by the Joanna Briggs Institute. One synthesis revealed that visiting hours were seen as guidelines for the benefit of nurse and patient, rather than rules or policy. Due to the various types of designs in the available studies, it was not possible to pool quantitative research study results into a statistical meta-analysis. Because statistical pooling was not possible, the findings are presented in a narrative form. Following this, results are presented for their congruence with the principles of PFCC. CONCLUSION: Flexible visiting policies provide the ability to incorporate the concepts of PFCC into practice. However, nurses believe that while visiting is beneficial to patients, open and/or flexible visiting hours are an impediment to practice and increase their workload. Recommendations for best practice were formulated based on the outcomes and include visiting hours should be used as guidelines, not rules, that allow flexibility dependent upon individual patient/family situation. With regard to congruence with PFCC, patient and family requests for information emerged as an unmet need that needs to be addressed. PMID- 22093388 TI - Experiences of registered nurses as managers and leaders in residential aged care facilities: a systematic review. AB - BACKGROUND: The phenomenon of an ageing population is being experienced globally, as countries struggle to change and improve residential models of care and provide services to the elderly. The role of the registered nurse (RN) is considered crucial to the clinical governance and management of care given. To date, however, no systematic review has examined the RN's experience in leadership and management. OBJECTIVES: The objective of this review is to critically appraise, synthesise and present best available evidence on the experiences of RNs as clinical leaders and managers in residential aged care facilities. INCLUSION CRITERIA: This review considered qualitative research papers that addressed the experiences of RNs as clinical leaders and managers in residential aged care facilities. Participants of interest were RNs, nurse leaders, nurses holding registration and or regulation under a board of nursing, nurses working in residential aged care and long-term care facilities. The diversity and use of language to describe nurses' roles and models of care for the elderly care environment were considered in the review. SEARCH STRATEGY: The search strategy sought to find both published studies and papers, limited to the English language and published between January 1997 and February 2011. An initial limited search was done in Medical Literature Analysis and Retrieval System Online (MEDLINE) and Cumulative Index to Nursing and Allied Health Literature databases to identify the key words contained in the title or abstract and index terms used to describe the relevant terms in the article. A second extensive search was undertaken and extended to other relevant databases using all identified keywords and index terms. The third step involved searching reference lists and bibliographies of chosen articles for additional studies. METHODOLOGICAL QUALITY: Each paper was assessed by two independent reviewers for methodological quality prior to inclusion in the review using an appropriate critical appraisal instrument from the System for the Unified Management, Assessment and Review of Information package. As both reviewers were in agreement on all studies included, a third reviewer was not required. RESULTS: A final total of eight papers, qualitative in nature, were included in the review. The majority of papers examined the experiences of nurses' leadership styles and the management characteristics within their organisations. The qualitative papers were analysed using The Joanna Briggs Institute-Qualitative Assessment and Review Instrument.The process of meta-synthesis embodied in this programme involves the aggregation or synthesis of findings or conclusions. Five syntheses were derived with key themes related to education, professional nursing development, positive attitudes to aged care and the need for a supportive environment. CONCLUSION: Nurses that work in the aged care environment show a strong motivation to work in care and provide the best outcomes in nursing the elderly. Geriatric nursing is considered a specialised and complex area of healthcare by the nursing profession. Nurses experience a lack of professional support and collaboration from allied health and medical colleagues. There is a lack of specific education that is focused in clinical leadership and health team management. There is no current structured pathway of learning and development for nursing careers in aged care. Nurses identify with their leadership role in residential aged care, and experience paradoxical feelings of being valued by the clients and devalued by the system at the same time. Organisational barriers are strong in preventing continuing education and skills development for nurse leaders in aged care environments. IMPLICATIONS FOR PRACTICE: Overall the themes presented in the review reported the negative experiences of nurses in residential aged care and geriatrics. Nurses will continue to be devalued if there is no professional identity and support for their roles and need to have a career pathway when making the decision to enter into aged and geriatric practice. Clinical leadership training is needed for nurses to transition through practice into specialised roles such as the RN team leader and Geriatric Nurse Practitioner (GNP). Providing a career structure and choice in the industry for the nurse to become a clinical leader or a manager of health services will improve recruitment and retention. IMPLICATION FOR RESEARCH: More research is needed to identify the skills gaps experienced by nurses in aged care and geriatric care. This research could lead to the design and implementation of a skills audit to identify candidates for specialised courses so that clinical leadership and governance in aged care are improved. More research is needed for role construction and the professional development of the GNP. Organisations can benefit from research currently being conducted on the role of the RN in aged care and geriatrics, by mapping the skills mix of candidate RNs to the key performance indicators in the role. Organisations must change their perception and value of RNs as clinical leaders in care teams. PMID- 22093389 TI - Comprehensive systematic review of healthcare workers' perceptions of risk and use of coping strategies towards emerging respiratory infectious diseases. AB - AIM: To determine healthcare workers' perceptions of risk from exposure to emerging acute respiratory infectious diseases and the perceived effectiveness of strategies used to facilitate healthy coping in acute hospital and community healthcare settings. METHODS: Electronic databases (Cumulative Index to Nursing and Allied Health Literature, Ovid, PubMed, ScienceDirect, Scopus and Wiley InterScience) were searched using a three-step search strategy to identify the relevant quantitative and qualitative studies published in English from 1997 to 2009. The grey literature was not included in the review. The identified studies were evaluated using the Meta-Analysis of Statistics, Assessment and Review Instrument and the Qualitative Assessment and Review Instrument from the Joanna Briggs Institute. Fourteen quantitative studies were included and the findings included in a narrative summary. The findings from the two qualitative studies were categorised into a meta-synthesis that generated two synthesised findings. RESULTS: Findings indicated that healthcare workers perceived personal and familial health risks and stigmatisation from their exposure to emerging acute respiratory infectious diseases, but the majority were accepting of these risks. Organisational implementation of infection control measures, avoidance of patients and complying with personal protective equipment were identified as risk mitigating strategies. Demographic, individual and organisational factors were found to influence their risk perceptions and their adoption of strategies to mitigate the risk. CONCLUSIONS: It appears that healthcare workers' risk perceptions can influence their behaviour towards patients with emerging acute respiratory infectious diseases as well as their use of risk-mitigating strategies. Institutions need to ensure that appropriate infection control safeguards are in place to protect workers and their families. Institutions can also offer incentives to encourage healthcare workers to comply with the policies and procedures introduced to mitigate risk. IMPLICATIONS FOR PRACTICE: Institutions and government need to ensure that policies and procedures are communicated and adequate institutional measures (i.e. personal protective equipment; education and training; and personal support) are implemented to safeguard healthcare workers during and after pandemic outbreaks. IMPLICATIONS FOR RESEARCH: Future research needs to examine how perception of risk related to acute emerging respiratory infectious diseases, epidemic or pandemic, and the factors that would influence healthcare workers': decisions to stay within the workforce and provide care or resign from the workforce and compliance with institutional and government policies and procedures, as well as compliance to use of personal protective equipment. PMID- 22093390 TI - Prevalence of obesity among migrant Asian Indians: a systematic review and meta analysis. AB - OBJECTIVE: The objective of this review was to investigate the prevalence of obesity among migrant Asian Indians globally. The primary outcomes of interest included the incidence of obesity as measured objectively by body mass index (BMI), waist circumference, waist-to-hip ratio and body fat. METHODS: All published studies that investigated obesity rates in migrant Asian Indians were considered for inclusion in the review. Studies were included if they had more than 100 participants and reported objective measures of obesity. A literature search was performed using the following databases Medline (2000-10), Cumulative Index to Nursing and Allied Health Literature (2000-11), Excerpta Medica Database (2000-current) and the Cochrane Controlled Studies Register (Issue 1, 2011 of Cochrane Library). In addition, the reference lists of relevant studies and conference proceedings were also scrutinised. Two reviewers independently assessed the eligibility of the studies for inclusion in the review, the methodological quality and then extracted details of eligible studies. Data were analysed using the Review Manager software. RESULTS: Ten studies investigating the obesity indices in Asian Indians were eligible for this review. All ten trials that reported on BMI values demonstrated significantly higher BMI values among migrant Asian Indians when compared with other migrants and the native population (standardised mean difference 0.36; 95% confidence interval 0.30, 0.41). A greater proportion of Asian Indians had BMIs greater than or equal to 30 when compared with other ethnic groups. Up to 80% of the Asian Indian women had a waist circumference greater than the recommended value of 88 cm. CONCLUSIONS: Based on the available evidence, the obesity indices among migrant Asian Indians are significantly greater when compared with the native population and those living in India, particularly among women. This is likely to contribute to the high levels of diabetes and coronary heart disease in this population. Culturally appropriate strategies to reduce obesity, particularly abdominal obesity, in this ethnic group are urgently needed. PMID- 22093391 TI - Skin tear prevention and management among patients in the acute aged care and rehabilitation units in the Australian Capital Territory: a best practice implementation project. AB - BACKGROUND: A skin tear is a traumatic wound that results from the separation of the skin layers due to shearing forces, friction or blunt trauma that affects all people. Numerous preventative measures aim to reduce the skin tears and minimise conditions that predispose the epidermis to injury. With the increasing elderly population in acute aged care, implementation of an evidence-based guideline is critical as changes to ageing skin integrity make this population more susceptible to skin tear. AIMS/OBJECTIVES: The aim of this project was to ensure the practice of skin tear assessment, prevention and management among acute aged care causes and rehabilitation patients was performed according to best available evidence. METHODS: This project utilised a pre- and post-implementation audit design using the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice programs. The project was conducted from June to November 2010 with the audits conducted in the acute aged care and rehabilitation units of two public hospitals in the Australian Capital Territory involving a sample size of 96 patients at pre-audit and 95 patient at post-audit admitted during the audit period. A convenience sample of 20 nurses also consented to be observed. The audits were conducted after obtaining ethics approval and consent from patients and nurses. RESULTS: The results showed a significant change in compliance to the skin tear guidelines at post implementation audit. Staff education in particular had a dramatic increase from 20% to 98% and the point prevalence rate of hospital-acquired skin tear decreased from 10% to 0.15%. DISCUSSION/CONCLUSION: This project emphasised the importance of education of all personnel involved in patient care and that a simple assessment of skin integrity is critical in preventing and managing skin tear especially among the susceptible elderly population. PMID- 22093392 TI - Drinking speed using a valved Pat Saunders straw, wide bore straw and a narrow bore straw in school-age children. AB - BACKGROUND: To understand the nature of straw drinking in relation to a group of children with specific eating and drinking difficulties, it is first necessary to ascertain the range of normal function. Straw drinking is often recommended as a method that can support children with eating and drinking difficulties. METHOD: This study looked at straw drinking performance in a normal population of 125 children aged between 6 and 11 years of age. Three types of straws were used: a valved Pat Saunders straw, a wide bore straw and a narrow bore straw. Children drank 40 mL of water for each straw tested. RESULTS: Children increased their speed of intake significantly for all straw types as they matured. Drinking speed was quickest for the wide bore straw followed by the narrow bore and slowest for the valved Pat Saunders straw. This was supported by qualitative feedback from the children with most finding the wide bore straw the easiest one to use and the valved Pat Saunders straw the hardest. There were significant differences in speed of flow between the valved Pat Saunders straw and wide bore straw, between the valved Pat Saunders straw and the narrow bore straw and between the wide bore straw and the narrow bore straw. There were no significant differences between straw flow or straw type and gender. CONCLUSIONS: This normative data for straw drinking in a paediatric population can be used to develop baseline measures for clinical assessment. PMID- 22093393 TI - New anti-epileptic drugs: overcoming the limits of randomised controlled trials. AB - This commentary focuses on the designs of randomised controlled trials of new anti-epileptic drugs as treatment for focal epilepsy. Limits of these trials, with particular focus on placebo-controlled designs, are discussed and strategies to overcoming them proposed. To date there are only few head-to-head comparison trials between new anti-epileptic drugs. Ideally, direct head-to-head comparisons of new anti-epileptic drugs should be available in order to get the whole picture of each treatment, but usually randomised controlled trials have not such a direct-comparison design. Multiple-treatment meta-analysis may represent a promising way of overcoming this limit, providing information on ranking efficacy of new anti-epileptic drugs, thus allowing to answer several relevant questions regarding daily practice and decision-making. Although not free from concerns, also historical design trials might have several advantages in that all patients receive a promising anti-epileptic drug at dose(s) that are expected to be fully effective and eliminate the need for a parallel group on suboptimal treatment or placebo. All these strategies aimed to overcome the lack of head-to-head comparisons can't anyway be considered as a substitute for properly conducted direct-comparison randomised trials, which remain the most relevant source of data to inform clinical decisions. PMID- 22093394 TI - Comparison of the effects of using the Crowe Critical Appraisal Tool versus informal appraisal in assessing health research: a randomised trial. AB - In systematic reviews, evidence-based practice and journal clubs critical appraisal tools are used to rate research papers. However, little evidence exists on whether the critical appraisal tool, subject matter knowledge or research design knowledge affect the appraisal of research papers. A match paired randomised trial was conducted in August/September 2010 in the Faculty of Medicine, Health and Molecular Science, James Cook University, Australia. Ten participants in total were randomly assigned to two groups using either an informal appraisal of research (IA group) or the Crowe Critical Appraisal Tool (CCAT group), a general critical appraisal tool. Participant independently appraised five research papers, where each paper had a different research design. The scores allocated to the papers by each group were analysed. The intraclass correlation coefficient for absolute agreement was 0.76 for the informal appraisal group and 0.88 for the Crowe Critical Appraisal Tool group. The G study showed that in the informal appraisal group 24% of variance in scores was attributable to either the rater or paper * rater interactions, whereas this was 12% in the Crowe Critical Appraisal Tool group. Analysis of covariance showed that there were statistically significant results in the informal appraisal group for subject matter knowledge (F(1,18) = 7.03, P < 0.05 1 tailed, partial eta2 = 0.28) and rater (F(4,18) = 4.57, P < 0.05 1 tailed, partial eta2 = 0.50). Kendall's tau correlation coefficient also showed a significant weak positive relationship (tau = 0.38, P = 0.03) between total score and subject matter knowledge for the informal appraisal group. The Crowe Critical Appraisal Tool was more reliable than an informal appraisal of the research papers. In the informal appraisal group, there were significant effects for rater and subject matter knowledge, whereas the Crowe Critical Appraisal Tool almost eliminated the rater effect, and no subject matter knowledge effect was apparent. There was no research design knowledge effect in either group. The Crowe Critical Appraisal Tool provided much better score reliability and should help readers with different levels and types of knowledge to reach similar conclusions about a research paper. PMID- 22093395 TI - Treatment of periodontal infection does not reduce the rates of poor pregnancy outcomes. PMID- 22093402 TI - The spiral flap for nasal alar reconstruction: our experience with 63 patients. AB - OBJECTIVE: To describe our patient selection, design, execution, and results with the spiral flap for distal nasal surgical defects after Mohs micrographic surgery. MATERIALS AND METHODS: We performed a retrospective analysis of all spiral flaps performed over a 5-year period. Sixty-three patients were identified, and charts and photographs were examined. Surgical defects were classified according to alar location. All follow-up encounters were reviewed to assess for complications and need for revisionary procedures. Intraoperative photographs were taken of representative cases to describe the surgical technique. RESULTS: Sixty-three patients on whom the spiral flap was performed were identified over a 5-year period. The flap was used to successfully reconstruct alar defects ranging in size from 5 to 15 mm in diameter. No persistent complications were noted. CONCLUSION: The spiral flap is a reproducible, one-stage flap for small to medium-sized defects of the nasal ala and alar groove that consistently produces topographic restoration with minimal risk of aesthetic or functional complication. PMID- 22093403 TI - Multidrug and carbapenem-resistant Acinetobacter baumannii infections: Factors associated with mortality. AB - BACKGROUND AND OBJECTIVE: To analyse factors related to mortality and influence of antibiotic treatment on outcome in patients with nosocomial infection due to multidrug and carbapenem-resistant Acinetobacter baumannii (MDR-C AB). PATIENTS AND METHODS: Observational and prospective study of a cohort of adult patients with MDR-C AB infection. Data collection from clinical records was done according to a standard protocol (January 2007 through June 2008). Patients with MDR-C AB infection were identified by review of results of microbiology cultures from the hospital microbiology laboratory. Epidemiological and clinical variables and predictors of mortality were analysed. RESULTS: 24 out of 101 cases were considered colonizations and 77 infections (27 bacteraemia); global mortality in infected patients was 49% (18 cases with bacteraemia and 20 with no bacteraemia). In the multivariate analysis, including the 77 cases of infection, the prognosis factors associated with mortality were age (OR 1.09; 95% CI 1.02-1.2), McCabe 1 (OR 33.98; 95% CI 4.33-266.85), bacteraemia (OR 9.89; 95% CI 1.13-86.13), inadequate empiric treatment (OR 16.7; 95% CI 2.15-129.79), and inadequate definitive treatment (OR 26.29; 95% CI 1.45-478.19). In the multivariate analysis including the 57 cases of infection with adequate definitive treatment, the prognosis factors associated with mortality were McCabe 1 (OR 24.08; 95% CI 3.67 157.96) and monotherapy versus combined treatment (OR 7.11; 95% CI 1.63-30.99). CONCLUSIONS: Our cohort of patients with MDR-C AB infection is characterised by a very high mortality (49%); the severity of patients and inadequate treatment or monotherapy are statistically associated with mortality. PMID- 22093404 TI - [Hereditary colorectal cancer]. AB - Up to 5% of all diagnosed colorectal cancers has a hereditary cuase. Colon cancer arise in younger individuals, and extracolonic tumors are also frequent. A precise understanding of main syndromes will allow the proper management of these patients, including genetic counselling, screening and prophylactic surgery. PMID- 22093405 TI - [Carbohydrate antigen 125 serial measurements after an admission for acute heart failure and risk of early readmission]. AB - FUNDAMENT AND OBJECTIVES: The early readmission after a hospitalization for acute heart failure (AHF) is frequent; however, factors associated are not clearly established. Plasma levels of carbohydrate antigen 125 (CA125) have shown to be associated with the presence of systemic congestion and increased risk of death in patients with AHF. The aim of this study was to assess the relationship between CA125 levels (during hospitalization, at the first outpatient visit or their changes) and readmission for AHF at 6 months follow up. PATIENTS AND METHOD: We analyzed 293 consecutive patients hospitalized for AHF in which CA125 was determined during the index hospitalization (T1) and the first outpatient visit after discharge (T2) (median 31 days). We examined the relationship between CA125 levels, both isolated determinations as their serial changes (absolute, relative or categorical) and readmission for AHF by Cox regression analysis adjusted for competing events. The reclassification technique integrated discrimination improvement (IDI) index was used to assess the additional discriminative power of this biomarker over the final multivariate model. RESULTS: At 6 months follow up, we identified 32 (10.9%) and 54 (18.4%) deaths and readmissions for AHF, respectively. CA125 categorical changes [decrease and normalization (C1, n=153), decrease but no normalization at T2 (C2, n=72) and increase, with high levels at T2 (>35 U/ml) (C3, n=68)], followed by the isolated determination of CA125 at T2, showed the best discriminative accuracy. Thus, with respect to patients in the C1 category, patients in categories C2 and C3 showed a higher risk of readmission for AHF: C2 vs. C1: HR=3.48, 95% CI:1.84-6.59, p<0.001; C3 vs. C1: HR=3.18, 95% CI:1.62-6.21, p=0.001. On the other hand, patients with elevated levels of CA125 in T2 (>35 U/ml) (41%) tripled the risk of readmission for AHF at 6 months compared with those with normal levels of CA125 at T2: HR=3.06, 95% CI:1.79-5.23, p<0.001. The addition of the categories of serial measurements of CA125 and the presence of elevated levels of CA125 at T2 showed a significant increase in the discriminating power of 6.27% and 6.17% in the IDI index, respectively. CONCLUSIONS: After an episode of AHF, the elevation of CA125 levels (>35 U/ml) after the first weeks of admission is associated with an increased risk of readmission for AHF. PMID- 22093406 TI - [Glycaemic management in type 1 and 2 diabetes patients undergoing interventional cardiology procedures. Heart and Diabetes Working Group. Sociedad Espan~ola de Cardiologi'a. Sociedad Espan~ola de Diabetes]. AB - Despite the growing number of therapeutic alternatives available as well as general reviews and treatment guidelines for the treatment of diabetes, physicians are often left without a clear pathway of therapy to follow in specific clinical contexts such as interventional cardiology. The present document proposes a consensus treatment algorithm, based both on a critical appraisal of evidence from recent clinical trials and on value judgements supported by the authors' collective clinical knowledge and experience, in an attempt to guide practitioners when choosing the most appropriate alternatives in the context of glycemic management in type 1 and 2 diabetic patients scheduled to undergo interventional cardiology procedures in a haemodynamic laboratory. PMID- 22093407 TI - [Cutaneous involvement in systemic Chagas disease in immunocompromised patient]. PMID- 22093408 TI - [Abdominal pain and wall distension as the onset form of neuroborreliosis]. PMID- 22093409 TI - The development of LENTICULESTM as reference materials for noroviruses. AB - AIMS: To investigate the potential for LENTICULESTM to act as reference materials (RMs) for noroviruses (NoV) [genogroups I (GI) and II (GII)] by determining their homogeneity and stability characteristics. METHODS AND RESULTS: NoV used in this study originated from human faecal material, screened for the absence of other faecally transmitted pathogens. The norovirus strains present in the faecal material were characterized by sequencing, and samples containing GI and GII strains representative of genotypes commonly circulating in the community were selected. RMs were produced utilizing modified lenticulating technology. A batch comprising 500 LENTICULESTM containing both norovirus genogroups was produced according to ISO Guide 34. The batch was tested and quantified using an ISO 17025 accredited quantitative real-time RT-PCR assay. Sufficient homogeneity was established using procedures described by Fearn and Thompson (2010), while stability at less than -15 degrees C and ambient temperature (17-22 degrees C) was assessed over 52 weeks and 7 days, respectively. CONCLUSIONS: Lenticulation was shown to be an effective means of preservation of detectable NoV. LENTICULESTM were sufficiently homogeneous and stable throughout medium-term frozen and short-term storage at room temperature to serve as RMs. Virus LENTICULESTM have the advantages of being easy to manipulate, provide assigned values and do not require the manipulation of high titre clinical material. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study show that norovirus LENTICULESTM can be used as stable RMs for quantitative real-time RT PCR assays. They can be utilized as in-run positive extraction controls and potentially for method calibration and to enable more easy comparison of data generated by the variety of differing norovirus determination methods that have emerged in recent years. LENTICULESTM have the potential to provide essential elements of laboratory quality assurance systems for laboratories implementing these new methods for virus testing in foodstuffs and for those running routine analyses. PMID- 22093410 TI - IL28B: relevance extended to hepatitis B virus or limited to interferon-based therapies in hepatitis C virus? PMID- 22093411 TI - Steatotic liver: a suitable source for the isolation of hepatic progenitor cells. AB - BACKGROUND: Alternative and/or complementary sources of cells such as hepatic progenitor cells (HPC) are under investigation for hepatic cell therapy purposes. Steatotic livers are those most commonly rejected for clinical transplantation and are also unsuitable for good quality hepatocyte isolation. AIM: Taken together these two facts, our aim was to investigate whether they could represent a suitable source for the isolation of progenitor cells. METHODS: Rats fed for 7 weeks with methionine-choline deficient diets showing proved steatotic signs (i.e. increase in hepatic lipids; macrovesicular steatosis) and steatotic and normal human liver samples were used to study the expression of HPC markers and to isolate these cells. RESULTS: In the liver of the steatotic rats there was a significant increase in HPC (known as oval cells in rodents) markers such as Thy 1, epithelial cell adhesion molecule (EpCAM) and OV-6 (2-, 3- and 5-fold increase respectively). Additionally, there was an increase in the yield of isolated oval cells compared to control rats. Similarly, studies using human livers clearly confirmed an increase in the expression of HPC markers in the steatotic tissue and a significant rise in the number of isolated progenitor cells (EpCAM+, Thy 1+, OV-6+) (10, 12 and 11.6 * 10(4) cells/g of tissue respectively). CONCLUSIONS: These data suggest that steatotic livers, discarded for orthotopic liver transplantation and hepatocyte isolation, could be a suitable source for large scale isolation of HPC which might be potential candidates in liver cell therapy. PMID- 22093412 TI - Fungal infection presenting as giant cell tubulointerstitial nephritis in kidney allograft. AB - Giant cell tubulointerstitial nephritis in the kidney allograft caused by infection is rare, and donor-transmitted infection in transplanted kidneys is also rare. In this case report, we describe an unusual histological manifestation of Candida albicans in the graft biopsy of a 53-year-old male kidney transplant recipient with decreased renal function 12 days post transplant. Several giant cells were present in the tubulointerstitial inflammation, as well as yeasts, with no evidence of rejection, and the histological diagnosis was confirmed by urine culture. Donor urine culture was positive for C. albicans, suggestive of a possible donor-transmitted infection. Prompt antifungal treatment eradicated the infection, and averted systemic spread. To our knowledge, there are no previous reports of Candida infection with giant cell tubulointerstitial nephritis in human renal allograft. PMID- 22093414 TI - [Importance of discipline construction in the development of key specialty]. PMID- 22093413 TI - Pyrosequencing of 16S rRNA gene amplicons to study the microbiota in the gastrointestinal tract of carp (Cyprinus carpio L.). AB - The microbes in the gastrointestinal (GI) tract are of high importance for the health of the host. In this study, Roche 454 pyrosequencing was applied to a pooled set of different 16S rRNA gene amplicons obtained from GI content of common carp (Cyprinus carpio) to make an inventory of the diversity of the microbiota in the GI tract. Compared to other studies, our culture-independent investigation reveals an impressive diversity of the microbial flora of the carp GI tract. The major group of obtained sequences belonged to the phylum Fusobacteria. Bacteroidetes, Planctomycetes and Gammaproteobacteria were other well represented groups of micro-organisms. Verrucomicrobiae, Clostridia and Bacilli (the latter two belonging to the phylum Firmicutes) had fewer representatives among the analyzed sequences. Many of these bacteria might be of high physiological relevance for carp as these groups have been implicated in vitamin production, nitrogen cycling and (cellulose) fermentation. PMID- 22093415 TI - [Challenge and tactical solution of off-label using antiepileptic drugs]. PMID- 22093416 TI - [Paying close attention to the misdiagnosis problems of childhood epilepsies]. PMID- 22093417 TI - [A multicenter controlled study on aripiprazole treatment for children with Tourette syndrome in China]. AB - OBJECTIVE: To evaluate the efficacy and safety of aripiprazole in the treatment of children with Tourette syndrome. METHOD: A prospective, multi-center, controlled clinical trial was conducted in 195 children aged 5-17 years with Tourette syndrome. The patients were assigned to two groups: aripiprazole group (n=98) and tiapride group (n=97), with the treatment dosage of 5-25 mg/d and 100 500 mg/d, respectively. After 12 weeks treatment, the clinical efficacy was assessed by the Yale Global Tic Severity Scale (YGTSS) score, and adverse reactions were observed by side effects symptoms scale, blood biochemical indexes, and electrocardiography. RESULT: Significant pre- and post-treatment differences were ascertained for motor tic, phonic tic, function damage and total scores of YGTSS in the both groups from the second week of treatment (P<0.0001). Compared with the tiapride group, the aripiprazole group showed a more significantly decreased function damage score of YGTSS by the second week of treatment (P<0.05). After 12 weeks treatment, total scores of YGTSS in the aripiprazole group decreased from 53.74+/-15.71 at baseline to 24.36+/-16.38, while in the tiapride group from 51.66+/-13.63 to 23.26+/-15.31. The mean reduction scores of YGTSS were 29.38 in the aripiprazole group and 28.40 in the tiapride group at the end of treatment, and the clinical response rates were 60.21% and 63.92%, respectively. There were no significant differences between the 2 groups (P>0.05). The incidence of adverse reactions was similar in the aripiprazole and tiapride groups, with 29.6% and 27.8% respectively. There were no significant differences in the incidence of adverse reactions between aripiprazole and tiapride groups and no severe adverse events were found in either group. CONCLUSION: The results showed that aripiprazole showed similar therapeutic effect to tiapride in treatment of children with Tourette syndrome. Aripiprazole was safe and well tolerated in Chinese population, and can be considered as a new valid option for the treatment of tic disorders. PMID- 22093418 TI - [Electroclinical features of myoclonic-atonic epilepsy]. AB - OBJECTIVE: To summarize the electroclinical characteristics of myoclonic atonic epilepsy (MAE) in children. METHOD: The clinical data, video electroencephalogram (EEG) and simultaneous electromyography (EMG) of MAE patients were analyzed. The treatment and its effects were followed up. RESULT: In 47 MAE patients, 25 had a history of febrile seizures (FS), 20 had a family history of FS or epilepsy. All patients had a normal development before the illness. The age of afebrile seizure onset was between 1.4 years to 5.8 years. The first seizure was generalized tonic clonic seizure (GTCS) in 41 patients (87.2%). All patients had multiple seizure types, including 47 GTCS (97.9%), 34 myoclonic atonic seizures (72.3%), 47 myoclonic seizures (100%), 32 atonic seizures (68.1%), 36 atypical absences (76.6%) and 3 tonic seizures (6.4%). EEG backgrounds were slow or parietal theta rhythm, interictal EEG showed 1-4 Hz (predominant 2-3 Hz) generalized spike and wave or poly spike and wave discharges in all cases. Seizures were controlled by antiepileptic drugs (AEDs) in 41 patients (87.2%). Valproate was used in 37. Lamotrigine was used in 26. Mild mental retardation was observed in 10 children after the onset of the illness. CONCLUSION: The clinical features of MAE included the following: the development was normal before the onset of the illness; the onset of seizure type was often GTCS. All patients had multiple generalized seizure types. Myoclonic atonic seizure was its characteristic seizure type. EEG showed generalized discharges. Early diagnosis and rational choice of AEDs are important for getting a better prognosis. PMID- 22093419 TI - [Follow-up study on the clinical characteristics and treatment effect of the different types of Guillain-Barre syndrome in children]. AB - OBJECTIVE: To study the clinical characteristics and effects of immunoglobulin treatment in children with the different types of Guillain-Barre syndrome (GBS). METHOD: Data of 108 patients hospitalized for GBS were retrospectively analyzed; 75 cases in this group were given acute high dose of gamma globulin (IVIG) 400 mg/(kg.d) intravenously for 5 d. Clinical and electrophysiological data and information on treatment and recovery of the children were collected during the follow-up and were analyzed. RESULT: According to the clinical and electrophysiologic findings, 32 patients manifested acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 34 had acute motor axonal neuropathy (AMAN), 3 had acute motor and sensory axonal neuropathy (AMSAN), 4 were inexcitable, 2 were unclassified. The clinical progress of the AMAN was faster than the AIDP group. Except for sensory nerve involvement, there was no significant difference in the clinical feature and severity. The mean time of the muscle strength began to recover was (5.59+/-3.63) days in the AIDP group and (7.21+/-4.68) days in the AMAN group after IVIG treatment. The time of the AIDP group was shorter than the AMAN group, but the difference was not statistically significant (t=-1.5702, P>0.05). The mean time of the muscle strength increased one grade was (8.88+/-4.39) days in the AIDP group and (12.67+/-8.35) days in the AMAN group. The difference was statistically significant (t=-2.3689, P<0.05). No patients in this group died. Follow-up data showed that the complete recovery time was not significantly different (t=0.2041, P>0.05). CONCLUSION: The clinical progress of the AMAN was faster than the AIDP group. Besides sensory nerve involvement, there was no significant difference in the clinical feature and severity. The AIDP group's clinical recovery was faster than AMAN's after the immunoglobulin treatment. The two groups were not significantly different in long term prognosis. PMID- 22093420 TI - [Adverse effects of antiepileptic drugs and their countermeasures in children]. PMID- 22093421 TI - [Emergency management of seizure and convulsive status epilepticus in children]. PMID- 22093422 TI - [The protocol of minimal residual disease in childhood acute lymphoblastic leukemia]. PMID- 22093423 TI - [Impact of pharmacogenetics on the drug therapy of epilepsy]. PMID- 22093424 TI - [Vascular endothelial cell dysfunction and its clinical strategy in severe sepsis]. PMID- 22093425 TI - [Copy-number variations of SHANK3 and related clinical phenotypes in children with autism]. AB - OBJECTIVE: To explore possible relationship between copy-number variations (CNVs) in 15q11-13, 16p11 and SHANK3 gene by using multiplex ligation-dependent probe amplification (MLPA) and the phenotypes in children with autism and to further explore the clinical application of MLPA to make an etiological diagnosis of Autism. METHODS: The diagnosed of autism was made according to the criteria of the ICD-10 and DSM-IV, with typical cluster of symptoms comprise social disability, communication impairments and repetitious behaviors. MLPA KIT P343-C1 AUTISM-1 was used to detect and describe the incidence of CNVs in these three domains. RESULTS: Among 109 cases collected from 102 autistic pedigrees, 2 individuals had SHANK3 microdeletion, accounting for approximately 2% (2/109) of cases, suggesting the proportion of SHANK3 microdeletion might contribute to typical autism. The phenotypic traits of patients with SHANK3 microdeletions showed homogenicity in severe core symptoms and mental retardation. CONCLUSIONS: SHANK3 microdeletion is an important genetics component for autism, which may explain 2% typical autism cases. SHANK3 microdeletion might explain autistic core symptoms and mental retardation. MLPA is a sensitive and a high throughput technique to detect CNVs in specific DNA segments, which is beneficial for further investigation of etiology of autism. PMID- 22093426 TI - [Severe sepsis as an initial presentation in children with Wernicke' s encephalopathy: report of a case and literature review]. AB - OBJECTIVE: Wernicke's encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine deficiency, which is associated with significant morbidity and mortality. The disorder is still greatly underdiagnosed in children because of either a relatively non-specific clinical presentation in some cases or unrecognized clinical setting. The aim of this literature review was to provide knowledge of pediatric WE in an effort to assist in early diagnosis, thereby reducing the morbidity and mortality. METHODS: The clinical manifestations, characteristic magnetic resonance imaging (MRI), diagnosis and treatment of one case and the other 35 cases reported in the last decade in children were summarized. RESULTS: Thirty-six cases (22 boys and 14 girls, 2 month to 16-year-old) were analyzed. All the other 35 cases except for our case had underlying diseases: improper feeding in 25/35 cases, long-time vomiting in 5/35 cases, immunosuppressive therapy in 4/35 cases, long-time total parenteral nutrition without multivitamin preparations supplementation in 3/35 cases and anorexia nervosa in 1/35 case. The classic triad (mental-status changes, nystagmus and ophthalmoplegia, and ataxia) was seen in 6/36 cases. The other clinical manifestations included consciousness disturbance in 24/36 cases, infection in 22/36 cases, pathological reflex and muscular tension changes in 18/36 cases, convulsion in 17/36 cases, developmental delay in 4/36 cases and failure to thrive in 2/36 cases. Cerebrospinal fluid examination was performed in 31/36 cases, and a slightly raised protein concentration was seen in 7/31 cases. The cerebrospinal fluid lactate levels were detected in 4/36 cases (all increased), serum lactic acid levels in 7/36 cases (6/7 cases increased), serum pyruvate in 4/36 cases (all increased), thiamine pyrophosphate effect (TPPE) in 9/36 cases (all increased), and serum thiamine in 2/36 cases (increased in 1/2 cases). The brain computed tomography (CT) scan was conducted in 20/36 cases and 16/20 cases showed abnormal hypodensity in bilateral basal ganglia, one case revealed diffuse cortical atrophy. The brain MR scan was conducted in 13/36 cases and all the 13 cases revealed symmetrical abnormal signal in bilateral mamillary body and basal ganglia, and 7/13 cases showed abnormal signals in the tegmentum of midbrain, cerebral aqueduct and white matter around the third and fourth ventricles. The diagnosis of WE was confirmed by MR in 12 cases, triad combined with MR in 3 cases, autopsy in 1 case among the 13 cases who underwent MR scan. The diagnosis of WE was confirmed by the TPPE and/or lactate levels in 9/11 cases. The initial thiamine was given by intravenous or intramuscular infusion in 33/36 cases, unknown method in 1 case, orally in 1 case and no thiamine was used in 1 case. The dosage of thiamine was 100 mg daily in 29/35 cases, unknown in 3/35 cases, 50 mg daily in 2/35 cases, 600 mg daily in 1/35 case. 34/35 patients' clinical symptoms improved during 24 hours to 1 week after initial treatment, and 1 case died due to no response to thiamine. Nineteen patients were followed up for 2-2.5 months and 17 cases recovered completely. CONCLUSION: Wernicke's encephalopathy can be difficult to diagnose because of a relatively non-specific clinical presentation. The characteristic MRI findings and the dramatic response of neurological signs to parenteral thiamine will assist early clinical diagnosis. Early and timely thiamine supplementation could reverse the clinical features and improve the prognosis in most cases. PMID- 22093427 TI - [Expert's Comment]. PMID- 22093428 TI - [Primary malignant airway neoplasms in 4 children]. AB - OBJECTIVE: Primary airway neoplasms are extremely rare in the pediatric age group. This paper reports 4 children with primary airway neoplasms to explore the clinical manifestations, safety and efficacy of bronchoscopic interventions. METHOD: The data of pathology, photographic documentation and imaging studies were analyzed. RESULT: Of the 4 reported lesions, 2 were characterized by low grade (2 with mucoepidermoid carcinoma) and 2 by high grade malignant (spindle cell carcinoma and malignant lymphoma). Onset of clinical manifestations occurred at the ages of 7 months to 7 years. All of them were initially misdiagnosed as bronchitis, asthma or atelectasis. The lesions located in trachea in 2 patients, in left bronchus of 1 patient and in right middle bronchus of 1 case. Atelectases occurred in bilateral bronchus where the lesions obstructed almost the entire lumen at the time of diagnosis. The diagnosis of airway masses depends upon maintaining a high index of suspicion, complemented by imaging and timely diagnostic endoscopy. The lesions were completely removed in 3/4 patients except 1 died during bronchoscopic procedures. CONCLUSION: The children with malignant airway neoplasms were presented with cough and wheezing without specific manifestations. Bronchoscopic interventions were effective in the treatment of non-operative cases. General anesthesia is strongly recommended for interventional bronchoscopy. PMID- 22093429 TI - [Clinical analysis of 18 cases with acute tumor lysis syndrome in children with B cell lymphoma]. AB - OBJECTIVE: To investigate risk factors associated with acute tumor lysis syndrome (ATLS) in children with B-cell lymphoma and to explore feasible means for the prophylaxis and treatment. METHOD: Data from 18 children with ATLS in B-cell lymphoma were collected to assess their tumor burden at diagnosis and before chemotherapy. Evaluation was performed at the 8th day, 3 month, and the end of chemotherapy and follow up. The incidence of ATLS in B-cell lymphoma, and the relationship between the incidence of ATLS and whether the kidney was involved and large tumor burden were analyzed respectively. All patients received hydration, alkalinization and received allopurinol routinely. Urate oxidase and hemodialysis treatment were administered in some cases. RESULT: Of the 103 children with B-cell lymphoma, 18 were diagnosed as having ATLS (17.5%). All the 18 cases with ATLS were histopathologically confirmed as having Burkitt's lymphoma. All the patients were at stage III or IV and all had large tumor sizes, and 7 were found to have blasts in the bone marrow>25% (38.9%). Lactate dehydrogenase (LDH) levels>=1000 U/L were found in 11 (61.1%) cases. All patients had developed metabolic abnormalities, including hyperuricemia, hyperphosphatemia, hypocalcemia, and uremia. In terms of clinical features and prognosis, all cases had nausea, vomiting, anorexia, oliguria, and anuria at different levels. One had gastrointestinal bleeding, 7 patients experienced seizures. The etiology in five was hypocalcemia and two had reversible posterior encephalopathy syndrome and all responded well to treatment. Nine cases of ATLS responded to supportive care, 4 required hemodialysis, and the other 4 responded to urate oxidase. Ten cases survived and 8 died. The major cause of death was severe complications and treatment was given up in 5 cases and recurrence occurred in 3 cases. CONCLUSION: ATLS was commonly seen in Burkitt's subtype of B cell lymphoma. Higher LDH and large tumor sizes and kidney involvement were important risk factors for the development of ATLS in children with B-cell lymphoma. Treatments with hydration, alkalinization and allopurinol were safe and effective. Urate oxidase and hemodialytic treatments should be given timely. PMID- 22093431 TI - [No. 133: Persistent cough for 7 months]. PMID- 22093430 TI - [Mutation of thyroid peroxidase gene in 35 patients with congenital hypothyroidism]. AB - OBJECTIVE: To identify thyroid peroxidase (TPO) gene mutations in 35 patients with congenital hypothyroidism. METHOD: Genomic DNA was isolated from peripheral blood samples of 35 patients with congenital hypothyroidism. All of the 17 exons and flanking introns of TPO gene were amplified by PCR, then the PCR products were sequenced bi-directionally and were analyzed by restriction endonucleases. RESULT: One patient had compound heterozygous mutations c.961A>G/c.2422delT, one was c.2268insT/c.1477G>A, and three was homozygous mutation c.2268insT. The TPO gene mutation c.961A>G [p. Thr321Ala] was one novel mutation. CONCLUSION: High frequency mutation in TPO gene was detected in patients with congenital hypothyroidism. PMID- 22093432 TI - [Gastric teratoma in infant: report of 3 cases]. PMID- 22093433 TI - [A case of chronic hematogenously disseminated tuberculosis]. PMID- 22093434 TI - [A severe case of avian-like H1N1 swine influenza virus infection in human]. PMID- 22093435 TI - System-level health disparities in California emergency departments: minorities and Medicaid patients are at higher risk of losing their emergency departments. AB - STUDY OBJECTIVE: Emergency department (ED) closures threaten community access to emergency services, but few data exist to describe factors associated with closure. We evaluate factors associated with ED closure in California and seek to determine whether hospitals serving more vulnerable populations have a higher rate of ED closure. METHODS: This was a retrospective cohort study of California hospital EDs between 1998 and 2008, using hospital- and patient-level data from the California Office of Statewide Health Planning and Development (OSHPD), as well as OSHPD patient discharge data. We examined the effects of hospital and patient factors on the hospital's likelihood of ED closure by using Cox proportional hazards models. RESULTS: In 4,411 hospital-years of observation, 29 of 401 (7.2%) EDs closed. In a model adjusted for total ED visits, hospital discharges, trauma center and teaching status, ownership, operating margin, and urbanicity, hospitals with more black patients (hazard ratio [HR] 1.41 per increase in proportion of blacks by 0.1; 95% confidence interval [CI] 1.16 to 1.72) and Medi-Cal recipients (HR 1.17 per increase in proportion insured by Medi Cal by 0.1; 95% CI 1.02 to 1.34) had higher risk of ED closure, as did for-profit institutions (HR 1.65; 95% CI 1.13 to 2.41). CONCLUSION: The population served by EDs and hospitals' profit model are associated with ED closure. Whether our findings are a manifestation of poorer reimbursement in at-risk EDs is unclear. PMID- 22093436 TI - Low back pain as the presenting sign in a patient with primary extradural melanoma of the thoracic spine--a metastatic disease 17 years after complete surgical resection. AB - Primary spinal melanomas are extremely rare lesions. In 1906, Hirschberg reported the first primary spinal melanoma, and since then only 40 new cases have been reported. A 47-year-old man was admitted suffering from low back pain, fatigue and loss of body weight persisting for three months. He had a 17-year-old history of an operated primary spinal melanoma from T7-T9, which had remained stable for these 17 years. Routine laboratory findings and clinical symptoms aroused suspicion of a metastatic disease. Multislice computed tomography and magnetic resonance imaging revealed stage-IV melanoma with thoracic, abdominal and skeletal metastases without the recurrence of the primary process. Transiliac crest core bone biopsy confirmed the diagnosis of metastatic melanoma. It is important to know that in all cases of back ore skeletal pain and unexplained weight loss, malignancy must always be considered in the differential diagnosis, especially in the subjects with a positive medical history. Patients who have back, skeletal, or joint pain that is unresponsive to a few weeks of conservative treatment or have known risk factors with or without serious etiology, are candidates for imaging studies. The present case demonstrates that complete surgical resection alone may result in a favourable outcome, but regular medical follow-up for an extended period, with the purpose of an early detection of a metastatic disease, is highly recommended. PMID- 22093437 TI - Estrogen modulates inhibition of return in healthy human females. AB - Estrogen has a key role in explaining gender differences in dopaminergic functioning. To date, previous studies on estrogen have focused on inhibitory output control, such as the intentional suppression of overt pre-potent actions, but whether input control is also modulated is an open question. For the first time, this study compared the ability to perform a cued target-detection task that measured inhibition of return (IOR), a reflexive inhibitory mechanism that delays attention from returning to a previously attended location, in young women (n=21) across the three phases of their menstrual cycle (salivary estradiol and progesterone concentrations were assessed) and in young men (n=21). Women showed more pronounced IOR effect in their follicular phase, which is associated with both higher estradiol levels and higher dopamine turnover rates, than in their luteal or menstruation phase. This increase in women's IOR in their follicular phase was also greater than the effect found for men at any of the three phases. Our results are consistent with the idea that estrogen promotes IOR. Given that the mechanism underlying IOR biases the cognitive system towards the intake of novel information, our findings suggest that when the estrogen level is high, women are biased towards cognitive flexibility rather than cognitive stability. We conclude that gender differences in inhibitory input control are variable and state-dependent but not structural. PMID- 22093438 TI - The neural correlates of coloured music: a functional MRI investigation of auditory-visual synaesthesia. AB - In auditory-visual synaesthesia, all kinds of sound can induce additional visual experiences. To identify the brain regions mainly involved in this form of synaesthesia, functional magnetic resonance imaging (fMRI) has been used during non-linguistic sound perception (chords and pure tones) in synaesthetes and non synaesthetes. Synaesthetes showed increased activation in the left inferior parietal cortex (IPC), an area involved in multimodal integration, feature binding and attention guidance. No significant group-differences could be detected in area V4, which is known to be related to colour vision and form processing. The results support the idea of the parietal cortex acting as sensory nexus area in auditory-visual synaesthesia, and as a common neural correlate for different types of synaesthesia. PMID- 22093439 TI - [HPV prophylactic vaccine coverage in France: Results of a survey among high school and university students in Marseilles' area]. AB - OBJECTIVE: To assess HPV prophylactic vaccine coverage among French high school and university students as well as their level of education about this vaccine. PATIENTS AND METHODS: An anonymous survey was conducted among 2500 high school and university students from the area of Marseilles, France, from December 2009 to April 2010. RESULTS: A total of 2018 questionnaires were collected (80.7% participation rate). Mean age of participants was 20 years (range, 15-45 years). Only 671 (35.4%) participants reported having been vaccinated against HPV, of whom 510 (73.4%) had completed the three injections scheme. Practice of cytological cervical cancer screening was not significantly influenced by vaccination status. Thus, 578 (45.2%) participants who had not been vaccinated already had had a cervical cytology performed, versus 295 (43.3%) vaccinated ones (P=0.445). Among those not being vaccinated, 671 (49.8%) fulfilled criteria for a catch-up vaccination, of whom only 325 (48.4%) agreed for such a catch-up. Main reasons given for refusal for a catch-up vaccination were the lack of information about HPV vaccine and fear of side effects. In total, 1722 (90%) considered themselves as educated about the HPV vaccine. Source of education was attributed to doctors and media by 54.4% and 53.7% of participants, respectively. Educational role attributed to school and university was poor (3.4%). CONCLUSION: Despite apparent satisfactory level of education, HPV prophylactic vaccine coverage among high school and university students appears to be insufficient. PMID- 22093440 TI - [Role of embolization in the management of uterine fibroids]. AB - Uterine artery embolization using non spherical PVA particles or calibrated trisacryl microspheres above 500 MUm is effective to treat menorrhagia, bulk related symptoms and pelvic pain in more than 90% of cases in the short-term. In the long-term, embolization is effective in 75% of cases at 5-7 years. At 6 months, uterine volume reduction and dominant fibroid volume reduction varies between 30-60% and 50-80% respectively. During hospital stay, the complication rate is 3%. Secondary hysterectomy for complication is less than 2% at 3 months. Definitive amenorrhea is reported in less than 5% of cases in women of less than 45 years of age. No significant impact of embolization on hormonal function has been reported in women less than 45 years with normal baseline function. Secondary hysterectomy for clinical failure or recurrence is reported in 14-28% of cases at 5 years. Non-spherical PVA particles are associated with more microcatheter occlusion than trisacryl microspheres. No difference between PVA particles and trisacryl microspheres was found in terms of post-embolization pain or analgesic doses. PVA microspheres (Contour SE et Bead Block) are associated with lower clinical success and lower fibroid devascularization using MRI than trisacryl microspheres. No difference between PVA particles and trisacryl microspheres was found in terms of clinical efficacy, uterine volume reduction and complication rate. Randomized studies comparing embolization to hysterectomy demonstrate that reinterventions are more frequently performed after embolization. Secondary hysterectomy is performed in 13 to 24% of cases at 2 years and in up to 28% of cases at 5 years. Hospital stay, duration of recovery and time off work are shorter after embolization compared to hysterectomy. Embolization is cheaper than hysterectomy at 12 and 24 months even taking into consideration the additional costs of imaging and reinterventions. Randomized studies comparing embolization to myomectomy demonstrate that in the short- and mid-term there is no difference in terms of control of menorrhagia and bulk related symptoms. Uterine volume reduction and quality of life were not different at 6 months. Periprocedural and 30-day complication rates are not different. At 6 months, the rate of complications is higher after myomectomy. Reinterventions are more frequent after embolization compared to myomectomy. Hospital stay, duration of recovery and time off work are shorter after embolization compared to myomectomy. Embolization should be considered with caution in pregnancy-seeking women since there is still a lack of good quality data available in the specific group of patients. FSH level is more frequently elevated after embolization compared to myomectomy. Pregnancy rate and term pregnancy rate are higher after myomectomy compared to embolization. Spontaneous abortion is more frequent after embolization than after myomectomy. There is no difference between embolization and myomectomy for the rates of pre-term delivery, cesarean section, post-partum hemorrhage, pre-eclampsia or intra-uterine growth retardation. Embolization performed before myomectomy (preoperative or combined procedures) can be discussed for an individual patient but there is not enough data to support its routine use. PMID- 22093441 TI - The ligamentum flavum at L4-5: relationship with anthropomorphic factors and clinical findings in older persons with and without spinal disorders. AB - OBJECTIVE: To examine the relationship between ligamentum flavum thickness and clinical spinal stenosis. DESIGN: A validation study. SETTING: Clinical research laboratory. PATIENTS: A total of 119 subjects from the Michigan Spinal Stenosis Study (MSSS). METHODS: Two new measurement techniques were compared by use of magnetic resonance images of 4 asymptomatic subjects by 2 examiners. The technique with the best interrater reliability was then used to measure the ligamentum flavum at L4-L5 in 119 subjects in the MSSS who, on the basis of clinical examination without imaging, were thought to have lumbar stenosis, mechanical back pain, or no pain. These findings were related to other radiologic findings, demographics, clinical severity, and electrodiagnostic findings. MAIN OUTCOME MEASUREMENTS: Perpendicular on the inside of the spinal canal from the deepest point of concavity of the lamina to the edge of the ligament. RESULTS: The ligamentum flavum width measurement had high interrater (r = 0.774) and intrarater (r = 0.768) reliability. In 28 asymptomatic volunteers, ligamentum flavum width averaged 5.72 +/- 0.95 mm, with the left side significantly thinner than the right (t = 2.117, P = .044), and thicker ligaments with age (r = 0.653, P < .001). Asymptomatic persons whom radiologists thought had stenosis had thicker ligaments (t = 2.273, P = .032). Persons with clinical stenosis (n = 48) and mechanical pain (n = 43) had ligament thickness similar to that of asymptomatic volunteers. Among patients with clinical stenosis, ligamentum flavum thickness did not relate to symptom severity (pedometer and laboratory ambulation tests, Pain Disability Index, and visual analog scale for pain). Most neurophysiological findings had no relationship with ligamentum flavum width, except the presence of limb fibrillation potentials related to a thinner ligament (t = 2.915, P = .004). CONCLUSIONS: The measurement technique is standardized for the ligamentum flavum for future use. Although the ligamentum flavum appears to get thicker with age, other factors, including clinical diagnosis, pain, and function, do not appear to relate to the ligamentum flavum width. PMID- 22093442 TI - Restraint of appetite and reduced regional brain volumes in anorexia nervosa: a voxel-based morphometric study. AB - BACKGROUND: Previous Magnetic Resonance Imaging (MRI) studies of people with anorexia nervosa (AN) have shown differences in brain structure. This study aimed to provide preliminary extensions of this data by examining how different levels of appetitive restraint impact on brain volume. METHODS: Voxel based morphometry (VBM), corrected for total intracranial volume, age, BMI, years of education in 14 women with AN (8 RAN and 6 BPAN) and 21 women (HC) was performed. Correlations between brain volume and dietary restraint were done using Statistical Package for the Social Sciences (SPSS). RESULTS: Increased right dorsolateral prefrontal cortex (DLPFC) and reduced right anterior insular cortex, bilateral parahippocampal gyrus, left fusiform gyrus, left cerebellum and right posterior cingulate volumes in AN compared to HC. RAN compared to BPAN had reduced left orbitofrontal cortex, right anterior insular cortex, bilateral parahippocampal gyrus and left cerebellum. Age negatively correlated with right DLPFC volume in HC but not in AN; dietary restraint and BMI predicted 57% of variance in right DLPFC volume in AN. CONCLUSIONS: In AN, brain volume differences were found in appetitive, somatosensory and top-down control brain regions. Differences in regional GMV may be linked to levels of appetitive restraint, but whether they are state or trait is unclear. Nevertheless, these discrete brain volume differences provide candidate brain regions for further structural and functional study in people with eating disorders. PMID- 22093443 TI - The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program. AB - Study Type--Prognostic (cohort). Level of Evidence 2b. What's known on the subject? And what does the study add? Previous studies have attempted to characterize the normal biological variability in PSA among men without prostate cancer. These reports suggest that PSA variability is unrelated to age, but there are conflicting data on its association with the baseline PSA level. There are limited published data regarding the effects of prostate volume on PSA variability. A prior study assessing whether prostate volume changes would confound the use of PSA velocity in clinical practice reported that prostate volume changes were not significantly related to PSA changes. This study did not directly address the effect of baseline prostate volume on serial PSA variability. The objective of the current study was to further examine the relationship between prostate volume and PSA variability. Our hypothesis was that larger baseline prostate volume would be associated with increased PSA variability in men without known prostate cancer and in those with suspected small-volume disease. The results of the study suggest that baseline PSA, not prostate volume, is the primary driver of PSA variability in these populations. OBJECTIVE: * To clarify the relationship between serial prostate-specific antigen (PSA) variability and prostate volume in both cancer-free participants from the Baltimore Longitudinal Study of Aging (BLSA) and patients with low-risk prostate cancer from the Johns Hopkins Active Surveillance Program (AS). MATERIALS AND METHODS: * In all, 287 men from the BLSA and 131 patients from the AS were included in the analysis, all with at least two PSA measurements and concurrent prostate volume measurements. * PSA variability was calculated in ng/mL per year, and a linear mixed-effects model was used to determine the relative effects of prostate volume, baseline PSA and age on PSA change over time. RESULTS: * In a model with prostate volume, age and baseline PSA, there was no significant relationship between prostate volume and PSA variability (BLSA, P= 0.57; AS, P= 0.49). * Only baseline PSA showed a significant relationship to PSA yearly variability (PSAYV) (P < 0.001). Specifically, a one unit higher baseline PSA (ng/mL) corresponded on average to 0.09 and 0.06 ng/mL per year higher PSAYV in the BLSA and AS populations, respectively. CONCLUSIONS: * The results of the present study suggest that the primary driver of PSA variability is the baseline PSA level, rather than prostate volume. * Clinicians might consider the baseline PSA level to help predict the expected variability in serial PSA measurements. PMID- 22093444 TI - Inhibition of the miR-143/145 cluster attenuated neutrophil differentiation of APL cells. AB - MicroRNAs can influence hematopoietic cell lineage commitment and aberrant expression of hematopoietic miRNAs contributes to AML pathology. We found that miR-143 and miR-145 expression is significantly repressed in primary AML patient samples as compared to neutrophils of healthy donors. Further analysis revealed impaired neutrophil differentiation of APL cells upon inhibition of miR-145 expression. Lastly, we identified p73 as transcriptional regulator of miR-143/145 during neutrophil differentiation of APL cells. Our data suggest that low miR-145 levels in APL, possibly due to aberrant expression of p73 transcription factors, contribute to the differentiation block seen in this disease. PMID- 22093445 TI - Epidemiology of injuries due to tropical cyclones in Hong Kong: a retrospective observational study. AB - BACKGROUND: Tropical cyclones are huge circulating masses of wind which form over tropical and sub-tropical waters. They affect an average of 78 million people each year. Hong Kong is a large urban centre with a population of just over 7 million which is frequently affected by tropical cyclones. We aimed to describe the numbers and types of injuries due to tropical cyclones in Hong Kong, as well as their relation to tropical cyclone characteristics. METHODS: The records of all patients presenting to Hong Kong's public hospital emergency departments from 1st January 2004 to 31st December 2009 with tropical cyclone related injuries were reviewed and information regarding patient and injury characteristics was collected. Meteorological records for the relevant periods were examined and data on wind speed, rainfall and timing of landfall and warning signals was recorded and compared with the timing of tropical cyclone related injuries. RESULTS: A total of 460 tropical cyclone related injuries and one fatality across 15 emergency departments were identified during the study period. The mean age of those injured was 48 years and 48% were female. 25.4% of injuries were work related. The head (33.5%) and upper limb (32.5%) were the most commonly injured regions, with contusions (48.6%) and lacerations (30.2%) being the most common injury types. Falls (42.6%) were the most common mechanism of injury, followed by being hit by a falling or flying object (22.0%). In univariable analysis the relative risk of injury increased with mean hourly wind speed and hourly maximum gust. Multivariable analysis, however, showed that relative risk of injury increased with maximum gust but not average wind speed, with relative risk of injury rising sharply above maximum gusts of greater than 20 m/s. Moderate wind speed with high gust (rather than high average and high gust) appears to be the most risky situation for injuries. Relative risk of injury was not associated with rainfall. The majority of injuries (56%) occurred in the 3h before and after a tropical cyclone's closest proximity to Hong Kong, with relative risk of injury being highest mid-morning. CONCLUSIONS: In tropical cyclone related injuries in Hong Kong the head and upper limb are the most commonly affected sites with falls and being hit by a falling or flying object being the most common mechanisms of injury. Hourly maximum gust appears to be more important that mean hourly wind speed in determining risk of injury. These findings have implications for injury prevention measures and emergency planning in Hong Kong and other regions effected by tropical cyclones. PMID- 22093446 TI - Out of control: an associative account of congruency effects in sequence learning. AB - The demonstration of a sequential congruency effect in sequence learning has been offered as evidence for control processes that act to inhibit automatic response tendencies (Jimenez, Lupianez, & Vaquero, 2009) via unconscious conflict monitoring. Here we propose an alternative interpretation of this effect based on the associative learning of chains of sequenced contingencies. This account is supported by simulations with a Simple Recurrent Network, an associative (connectionist) model of sequence learning. We argue that the control- and associative-based accounts differ in their predictions concerning the magnitude of the sequential congruency effect across training. These predictions are tested by reanalysing data from a study by Shanks, Wilkinson, and Channon (2003). The results support the associative learning account which explains the sequential congruency effect without appealing to control processes (either conscious or unconscious). PMID- 22093447 TI - Random KNN feature selection - a fast and stable alternative to Random Forests. AB - BACKGROUND: Successfully modeling high-dimensional data involving thousands of variables is challenging. This is especially true for gene expression profiling experiments, given the large number of genes involved and the small number of samples available. Random Forests (RF) is a popular and widely used approach to feature selection for such "small n, large p problems." However, Random Forests suffers from instability, especially in the presence of noisy and/or unbalanced inputs. RESULTS: We present RKNN-FS, an innovative feature selection procedure for "small n, large p problems." RKNN-FS is based on Random KNN (RKNN), a novel generalization of traditional nearest-neighbor modeling. RKNN consists of an ensemble of base k-nearest neighbor models, each constructed from a random subset of the input variables. To rank the importance of the variables, we define a criterion on the RKNN framework, using the notion of support. A two-stage backward model selection method is then developed based on this criterion. Empirical results on microarray data sets with thousands of variables and relatively few samples show that RKNN-FS is an effective feature selection approach for high-dimensional data. RKNN is similar to Random Forests in terms of classification accuracy without feature selection. However, RKNN provides much better classification accuracy than RF when each method incorporates a feature selection step. Our results show that RKNN is significantly more stable and more robust than Random Forests for feature selection when the input data are noisy and/or unbalanced. Further, RKNN-FS is much faster than the Random Forests feature selection method (RF-FS), especially for large scale problems, involving thousands of variables and multiple classes. CONCLUSIONS: Given the superiority of Random KNN in classification performance when compared with Random Forests, RKNN-FS's simplicity and ease of implementation, and its superiority in speed and stability, we propose RKNN-FS as a faster and more stable alternative to Random Forests in classification problems involving feature selection for high dimensional datasets. PMID- 22093448 TI - Treatment of melasma using a novel 1,927-nm fractional thulium fiber laser: a pilot study. AB - BACKGROUND: A 1,927-nm wavelength was recently added to the 1,550-nm erbium-doped fiber laser. This wavelength possesses a higher absorption coefficient for water than the 1,550-nm, conferring greater ability to target epidermal processes such as dyschromia. OBJECTIVE: To evaluate the efficacy and safety of a novel 1,927-nm fractional thulium fiber laser in the treatment of melasma. METHODS: Fourteen patients underwent three to four laser treatments (at 4-week intervals) at pulse energies of 10 to 20 mJ and total densities of 252 to 784 microscopic treatment zones per cm(2) (6-8 passes) using a 1,927-nm thulium fiber laser. Three blinded assessors and the patients evaluated clinical improvement of treatment areas at 1 , 3-, and 6-month follow-ups. Side effects were assessed, and pain was scored using a visual analog scale (0-10). RESULTS: A statistically significant 51% reduction in MASI score was observed at 1-month post 3 to 4 laser treatments. A 33% (p = .06) and 34% (p = .07) reduction in Melasma Area and Severity Index score was observed at the 3- and 6-month follow-up visits, respectively. Skin responses observed after treatment were moderate erythema and mild edema. No scarring or postinflammatory hyper- or hypopigmentation was observed. CONCLUSION: The 1,927-nm fractional thulium fiber laser is a safe, effective treatment for melasma. PMID- 22093449 TI - Development of a novel technique for axenic isolation and culture of thraustochytrids from New Zealand marine environments. AB - AIMS: To maintain axenic cultures of commercially important thraustochytrids, a novel procedure was developed for the isolation of zoospores and sporangium from heterotrophic seawater samples and axenic culture on solid media. METHODS AND RESULTS: Thraustochytrid cultures were isolated from Whangapoua Harbour in North East New Zealand and subjected to two antibiotic and antifungal treatment regimes designed to eliminate bacteria and fungi. Antibiotic trial 1 was designed to determine the appropriate combination of antibiotics (including streptomycin/penicillin, ampicillin, rifampicin, nalidixic acid, tetracycline, gentamicin and the antifungal agent nystatin). Antibiotic trial 2 determined the optimal dosing frequency and concentration of the antibiotics, and antifungal found to be the most promising in trial 1. Axenic cultures were then spread plated onto nutrient agar containing the optimal antibiotic cocktail, and pure thraustochytrid colonies were purified on solid media using standard microbiological techniques. CONCLUSIONS: Removal of bacteria and fungi was best accomplished using a mixture of three antibiotics and one antifungal; rifampicin (300 mg l(-1)), streptomycin/penicillin (25 mg l(-1)) and nystatin (10 mg l(-1)) were incorporated in seawater samples and incorporated into cultures every 24 h for a minimum of 2 days. SIGNIFICANCE AND IMPACT OF THE STUDY: The axenic isolation and culture of marine thraustochytrids from a marine habitat in New Zealand have significant implications for the biotechnological development of these potentially valuable protists. This method has global significance as it is reasonable to assume it could be used throughout the world to obtain axenic thraustochytrid cultures. PMID- 22093450 TI - Glucagon like-peptide 1 receptor and the liver. PMID- 22093451 TI - Understanding the relationship between PNPLA3, NAFLD and insulin resistance: do ethnic differences bring more questions or more answers? PMID- 22093452 TI - Minimal cooperation between mutant Hras and c-myc or TGFalpha in the regulation of mouse hepatocyte growth or transformation in vivo. AB - BACKGROUND: Liver carcinogenesis is associated with multiple genetic changes in affected cells, including alterations in the Hras signalling pathway. AIM: To define the biological contributions of Hras to mouse hepatocarcinogenesis, we quantified in vivo interactions between mutant Hras and other genetic alterations frequently associated with liver cancer, including overexpression of the transcription factor c-myc and the epidermal growth factor receptor ligand transforming growth factor alpha (TGFalpha). METHODS: To accomplish this aim, we initiated expression of an activated Hras in hepatocytes of adult mice with or without simultaneous overexpression of either c-myc or TGFalpha. Potential interactions also were assessed through the use of the comparative hepatocyte growth assay, a hepatocyte transplantation assay that measures effects of altered gene expression on hepatocyte growth in vivo. RESULTS: Hras expression caused diffuse liver enlargement (hepatomegaly), and this phenotype was not changed by coexpression of c-myc or TGFalpha. Using the transplant system, we found that expression of mutant Hras alone was sufficient to induce hepatocyte focus growth in a quiescent liver. Paradoxically, adding expression of TGFalpha or c-myc reversed this Hras effect. Finally, the frequencies of transplant foci with the preneoplastic feature of extreme growth potential and of liver neoplasms were increased for Hras and both combinations when compared with control hepatocytes, but did not differ among oncogene-expressing groups. CONCLUSIONS: Hras-associated hepatocyte growth deregulation is not complemented by activation of c-myc or TGFalpha growth signalling pathways in mouse liver. This finding emphasizes the tissue-specific character of molecular growth regulation. PMID- 22093453 TI - Different sites of xenoantigen delivery lead to a virally induced late-onset hepatitis in mice through molecular mimicry. AB - BACKGROUND: Epidemiological and laboratory evidences led to the hypothesis that molecular mimicry between viruses and self-proteins could be linked to the onset of autoimmune hepatitis (AIH). Hepatotropic viruses could be good candidates, as a pro-inflammatory environment may facilitate the development of AIH. AIMS: The aims of this study were to test a virus ability to induce an AIH through molecular mimicry and the influence of hepatic inflammation in this process. METHODS: C57BL/6 mice were injected i.v. or i.m. with recombinant adenoviral vectors (RecAdV) encoding for human type 2 AIH antigens to target xenoantigens expression in the liver and to create a transient hepatitis (i.v.) or for 'peripheral' xenoantigens expression (i.m.). Liver injury and B-cell response were evaluated. RESULTS: Late-onset hepatitis was observed 8 months after i.v. or i.m. RecAdV injections, despite presence or absence of an initial transient hepatitis. Intensity of B-cell response was similar for both type of injections, but the Ig isotypes produced were different. B-cell autoimmune response spread to several liver proteins. CONCLUSIONS: Liver autoimmune response can be initiated using molecular mimicry over a long period of time, validating the hit-and-run hypothesis. Initial liver inflammatory injury is neither necessary, nor detrimental to the development of AIH. These results highlight the significance of initial events on the pathogenesis of autoimmune liver injury. PMID- 22093454 TI - Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction. AB - BACKGROUND: Mitochondria are the main sites for fatty acid oxidation and play a central role in lipotoxicity and nonalcoholic steatohepatitis. AIMS: We investigated whether carnitine prevents free fatty acid (FFA)-induced lipotoxicity in vitro and in vivo. METHODS: HepG2 cells were incubated with FFA, along with carnitine and carnitine complexes. Mitochondrial beta-oxidation, transmembrane potential, intracellular ATP levels and changes in mitochondrial copy number and morphology were analysed. Otsuka Long-Evans Tokushima Fatty and Long-Evans Tokushima Otsuka rats were segregated into three experimental groups and fed for 8 weeks with (i) normal chow, (ii) a methionine choline-deficient (MCD) diet or (iii) an L-carnitine-supplemented MCD diet. RESULTS: Carnitine prevented FFA-induced apoptosis (16% vs. 3%, P < 0.05). FFA treatment resulted in swollen mitochondria with increased inner matrix density and loss of cristae. However, mitochondria co-treated with carnitine had normal ultrastructure. The mitochondrial DNA copy number was higher in the carnitine treatment group than in the palmitic acid treatment group (375 vs. 221 copies, P < 0.05). The carnitine group showed higher mitochondrial beta-oxidation than did the control and palmitic acid treatment groups (597 vs. 432 and 395 ccpm, P < 0.05). Carnitine treatment increased the mRNA expression of carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor-gamma, and carnitine-lipoic acid further augmented the mRNA expression. In the in vivo model, carnitine-treated rats showed lower alanine transaminase levels and lesser lobular inflammation than did the MCD-treated rats. CONCLUSIONS: Carnitine and carnitine-lipoic acid prevent lipotoxicity by increasing mitochondrial beta-oxidation and reducing intracellular oxidative stress. PMID- 22093455 TI - Fecal calprotectin is a useful screening parameter for hepatic encephalopathy and spontaneous bacterial peritonitis in cirrhosis. AB - OBJECTIVE: Bacterial translocation, causing intestinal inflammation, is one of the key mechanisms in the pathogenesis of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP) The presence of fecal calprotectin quantitatively relates to intestinal neutrophil migration and is therefore considered as a marker of intestinal inflammation. We aimed to assess the role of fecal calprotectin concentrations (FCCs) in diagnosing the onset and severity of HE and SBP. METHODS: Sixty-one cirrhotics were prospectively included. Forty-two subjects served as controls. Several complications of cirrhosis were diagnosed by reference methods. Stool samples were collected for measuring FCCs. Patients revealing other causes of abnormal calprotectin results, e.g. gastrointestinal bleeding or inflammatory bowel disease were excluded. Multivariate analysis of cirrhosis-associated complications and their relation to FCCs was performed. RESULTS: Fecal calprotectin concentrations were higher in cirrhotics compared with controls (P<0.001). Among cirrhotics, FCCs were elevated dependent on the severity of liver disease as assessed by Child- and model for end-stage liver disease-scores. The corresponding correlation co-efficients by Spearman's were 0.577 (P<0.001) and 0.303 (P=0.018) respectively. A correlation emerged between elevated FCCs and HE grading as measured by West-Haven criteria and critical flicker frequency (both P<0.001; sensitivity=0.94 and 0.93, specificity=0.95 and 0.89 respectively) and SBP (P<0.02; sensitivity=0.71, specificity=0.79). FCCs were higher in cirrhotic subjects with additional extra-intestinal inflammation (P<0.01; sensitivity=0.65, specificity=0.8). The Pearsons correlation coefficients were 0.190 and 0.164 revealing no influence (P=0.142 and P=0.207) of laboratory parameters of systemic inflammation on FCCs in cirrhotic subgroup. CONCLUSIONS: Fecal calprotectin concentrations serve as a screening tool for HE and SBP. Assessment of FCCs may faciliate grading of HE-severity. PMID- 22093456 TI - Hepatitis E virus: an underdiagnosed cause of chronic hepatitis in renal transplant recipients. AB - Hepatitis E virus (HEV) infection can evolve to chronic hepatitis in immunocompromised patients leading to rapidly progressive cirrhosis. Proper diagnosis is therefore important, as reducing immunosuppressive therapy can allow clearance of the virus. We report a case of chronic HEV infection in a renal transplant recipient that went undiagnosed for many years, discuss the therapeutic options, and review the current available literature. PMID- 22093458 TI - [History and current status of research and practices in the prevention and treatment of chronic diseases in China]. PMID- 22093457 TI - Ultrasound in the evaluation of enthesitis: status and perspectives. AB - INTRODUCTION: An increasing number of studies have applied ultrasound to the evaluation of entheses in spondyloarthritis patients. However, no clear agreement exists on the definition of enthesitis, on the number and choice of entheses to examine and on ultrasound technique, which may all affect the results of the examination. The objectives of this study were to first determine the level of homogeneity in the ultrasound definitions for the principal lesions of enthesitis in the published literature and second, to evaluate the metric properties of ultrasound for detecting enthesitis according to the OMERACT filter. METHODS: Search was performed in PUBMED and EMBASE. Both grey-scale and Doppler definitions of enthesitis, including describing features of enthesitis, were collected and metrological qualities of studies were assessed. RESULTS: After selection, 48 articles were analyzed. The definition of ultrasound enthesitis and elementary features varied among authors. Grey-scale enthesitis was characterized by increasing thickness (94% of studies), hypoechogenicity (83%), enthesophytes (69%), erosions (67%), calcifications (52%), associated bursitis (46%) and cortical irregularities (29%). Only 46% of studies reported the use of Doppler. High discrepancies were observed on frequency, type of probe and Doppler mode used. Face and content validity were the most frequently evaluated criteria (43%) followed by reliability (29%) and responsiveness (19%). CONCLUSIONS: Ultrasound has evidence to support face, content validity and reliability for the evaluation of enthesitis, though there is a lack of well-reported methodology in most of the studies. Consensus on elementary lesions and standardization of exam is needed to determine the ultrasound definition of enthesitis in grey-scale and in Doppler for future applications. PMID- 22093459 TI - [A review of metabolic syndrome: to give up or carry on further research]. PMID- 22093460 TI - [Research on the influencing factors of dietary behaviors among school students]. PMID- 22093461 TI - [Epidemiological investigation and comparison of three different diagnostic criteria regarding metabolic syndrome among population age 30 - 80 in Xinjiang Uigur areas]. AB - OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS) among Xinjiang Uigur population aged 30 - 80 and to compare the differences of the three diagnostic criteria used for MS. The three diagnostic criteria were developed by the National Cholesterol Education Program (ATP III), International Diabetes Federation (IDF) and Chinese Medical Association Diabetes Branch (CDS). METHODS: A cross-sectional study was conducted on 2053 Xinjiang Uigur people aged 30 - 80. The prevalence of MS and the degree of agreement were both calculated according to the three definitions. The results of MS components were also analyzed. RESULTS: (1) According to the three definitions (ATP III, IDF and CDS), the prevalence and adjusted prevalence rates of MS were 35.80% (29.64%), 39.41% (35.88%) and 23.72% (19.17%). (2) According to the three definitions (the ATP III, IDF and CDS), the prevalence rates of subjects who had at least 3 risk factors were 98.64%, 97.90% and 92.81%. (3) Among all the subjects with MS, the MS diagnostic criteria of ATP III and IDF were in good accordance with the Kappa index (0.7801), Youden index (0.7928) and the concordance rate (0.9026). CDS was in relatively weak agreement when comparing with other definitions (ATP III and IDF). CONCLUSION: Our findings revealed big differences regarding the prevalence rates, the degree of agreement and the aggregation of risk components on MS among Xinjiang Uigur population. The detection rate of IDF criteria on MS and the highest while detection rate of ATP III criteria on subjects presented at least 3 risk factors were the highest. The concordance of ATP III criteria and IDF seemed to be a better one. PMID- 22093462 TI - [Association between serum nitric oxide and hypertension among 1453 women in Suzhou]. AB - OBJECTIVE: To investigate the association between serum nitric oxide (NO) and hypertension among women in Suzhou. METHODS: Blood pressure, height, weight and waist circumference (WC) were measured and factors including smoking, alcohol intake, family history of hypertension were investigated and blood glucose, blood lipid, serum NO were tested among 1453 women aged >= 30 years who lived in Jinchang district of Suzhou. Association between serum NO and hypertension was analyzed by univariate and multivariate methods. RESULTS: The mean levels of serum NO in hypertensive and normotensive persons were 28.17 (17.42 - 45.30) umol/L and 27.56 (17.19 - 44.42) umol/L, respectively, with no significant difference between the two groups (P > 0.05). RESULTS: from multivariable logistic regression analysis showed that low serum NO was not associated with hypertension, after adjustment for confounders (OR = 0.979, 95%CI: 0.747 - 1.283). The mean levels of systolic blood pressure/diastolic blood pressure were 130.1/83.3, 128.5/82.7, 129.8/83.2 and 129.1/83.3 mm Hg for whose serum NO level were in the first, second, third and fourth quartile, respectively. The risk of hypertension did not change along with the elevated serum NO levels. Compared to the first quartile of serum NO, the risks of hypertension in the second, third and fourth quartile did not change after adjustment for confounders and OR were 0.988 (0.709 - 1.377), 1.001 (0.720 - 1.390) and 1.077 (0.774 - 1.499), respectively. CONCLUSION: The serum NO level was not associated with hypertension in women in Suzhou. PMID- 22093463 TI - [Estimation on the intangible cost and influencing factors for patients with hepatitis B-related diseases]. AB - OBJECTIVE: To estimate the intangible cost and associated factors on patients with hepatitis B-related diseases, so as to explore the differences of the three elicitation techniques on the 'willingness to pay approach' (WTP). METHODS: Face to-Face interviews were conducted to collect health economics-related information by trained investigators, using a structured questionnaire. WTP was employed to estimate the intangible cost while an open-ended question format, together with iterative bidding game and payment card were respectively used to elicit WTP for the hypothetical cure of hepatitis B-related diseases. A Multiple linear stepwise regression model was determined to identify those factors potentially affecting the intangible cost. RESULTS: A total of 564 subjects from 641 patients with hepatitis B-related diseases were identified for the inclusion of this study. The average annual intangible cost of patient with hepatitis B-related diseases was 54 320.4 Yuan (Ren Minbi). The intangible cost accounted for 53.0% of the total cost, which was much more than the proportions of the direct and indirect costs (38.5% and 8.5%, respectively). Among annual personal and the household income of the patient, proportions of intangible cost were 262.6% and 67.6% respectively, suggesting that the patients were under huge spiritual and psychological pressure. Response rate of the approach, combined open-ended questions with iterative bidding game, was the highest (76.6%) among the three elicitation formats. Considered the characteristics of data being gathered, the approach seemed to be more reasonable. Further studies were needed to examine the results yielded from other WTP elicitation formats. We also noticed that the progression of disease was associated with the increase of direct and indirect costs, but not with the intangible cost. Data from the multiple linear stepwise regression analysis indicated that the types of hospital and commercial medical insurance were significantly different in explaining the variation of the intangible cost. CONCLUSION: Measures should be taken to reduce the intangible cost of hepatitis B related diseases. The approach regarding the combination of open-ended questions with iterative bidding game should be recommended when carrying our further WTP studies of this kind. PMID- 22093464 TI - [A survey on the agricultural profession-related injuries among 11 902 rural residents in Shandong province]. AB - OBJECTIVE: To understand the prevalence and risk factors of agricultural activities related injuries among rural residents in Shandong province. METHODS: A retrospective investigation was conducted among agricultural profession-related workers in 20 villages with multistage cluster sampling method in Shandong province. Four times face-to-face interview were conducted by trained interviewers, including 32 students and local medical personnel under constructed questionnaires. Accidental injuries occurred in the activities or in the agricultural profession-related jobs were recorded, from May 1(st)2009 to April 30(st) 2010. Data was input and analyzed by SPSS 13.0 statistical software. RESULTS: A total of 837 cases reported at least 1 job-related injury out of the 11 902 people who had been surveyed in one year. The crude incidence rate was 7.03% and the standardized incidence rate was 7.36%, higher in males (9.01%) than in females (4.10%), chi2 = 105.53, P = 0.000. Children and adolescents (<= 14 aged) had the higher incidence rate (9.50%), chi2 = 9.70, P = 0.008. People working in the area of commercial service related to agricultural products had the highest incidence rate (12.94%). In particular, those occupations that related to agricultural construction or materials appeared to have had higher incidence rates as 16.80% and 15.59% respectively, than other kinds of jobs (chi2 = 167.30, P = 0.000). There were higher proportion of injuries occurred in the roads (28.79%), in the fields (28.08%)during labor work (38.00%) transportation (27.97%), respectively. The seasonality of agricultural injures mostly occurred between June and August, accounted for 47.43%. Major external causes related to injuries were instruments or tools (31.42%) being used, transportation (24.13%) and falls (20.19%). Wounds on limbs took the majority (56.39%). The accidental self-inflicted injury occupied 76.82%, while accidents to passive injuries occupied 11.47%, other kinds accounted for 11.71%. Most of the accidents caused mild or moderate damage, accounted for 60.22% and 30.34% respectively. 7 cases died of injuries, with the fatality rate as 0.84% and the mortality rate was 58.81 per one hundred thousand. 72 cases ended up in disability caused by injuries, with the morbidity rate as 6.05 per thousand. Answers to the major internal causes of injuries appeared to be: "did not know how to protect oneself" (29.87%) with females (45.41%) in particular, followed by"over fatigue" and "inappropriate treatment" which took the 2(nd) place in males. Major natural environmental factors of injuries would relate to "high air temperature and humidity but lower wind velocity" (14.93%), "unclear signs on the country road" (12.19%), "the sky was cloudy or dark" (10.87%), "slippery road caused by rain or snow" (10.51%), "kids were unintended" (10.27%) etc. Most of the wounded received treatment clinically (50.18%), with the percentile (P50) of medical cost as 182.76 RMB (Yuan). The proportion of inpatient was 27.72% and with percentile of time as P(50) = 7.57 day and cost as P(50) = 2840.00 RMB Yuan. The wounded had a rest of P50 = 5.9 days, with an indirect cost as P(50) = 233.16 RMB Yuan. CONCLUSION: The results of this study indicated that the incidence of agricultural profession-related injuries was high, with serious harm. Behavioral intervention and awareness of injuries should be enhanced, together with the improvement of environmental condition. PMID- 22093465 TI - [An epidemiological survey on the incidence of non-fatal injury and influencing factors among children under 5 years old in China]. AB - OBJECTIVE: To determine the incidence of non-fatal injuries and related influencing factors among children under 5 years old in China. METHODS: Data involving 10 819 children under 5 years old was from the Fourth National Health Service Survey of China. Injury-related indicators include: history of ever having had an injury, its frequency, cause, location and severity of the injury. A two-level Poisson regression was used to examine the significance of related socio-economic variables. RESULTS: The overall incidence rate of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The first three leading causes of non-fatal injuries were falls, animal bite, fire/burn among children under 1 year old, with the rates as 3.9, 1.8 and 1.8 per 1000 population, respectively. For children aged 1 to 4 years old, the first three leading causes were animal bite, fall, fire/burn with rates as 6.5, 6.0 and 2.9 per 1000 population, respectively. 83.0% and 69.0% of last injuries occurred at home for the above said two age groups. No disability was found among children younger than 1 year old who suffered from a nonfatal injury while for the 1 - 4 age group, the disability accounted for 1.0% of injury induced outcomes. After adjusting other variables, boys had 1.57 times the risk of injury compared with girls in the 1 - 4 age group (P < 0.05). The differences on the effects regarding ethnicity, per capita household income, and place were insignificant (P > 0.05). None of the socio-economic variables was found that significantly related to the non-fatal injury risk among children under 1 year old (P > 0.05). CONCLUSION: The incidence of nonfatal injuries among children under 5 years old was 16.0 per 1000 population in the prior 12 months. The three leading causes of injuries were animal bite, falls, fire/burn respectively. Home was the most common place that non-fatal injuries occurred. Boys had a higher risk of injury compared with girls among children aged 1 to 4 years old and the difference was significant. PMID- 22093466 TI - [Study on the status of unintentional injuries in children under age 7 in Guangzhou]. AB - OBJECTIVE: To understand the prevalence and distribution of unintentional injuries in children under age 7 in Guangzhou. METHODS: Data was descriptively analyzed from the Guangzhou Unintentional Injuries Surveillance System among 470 770 children under age 7 living scatter or collectively. RESULTS: The incidence rates of unintentional injuries among children in Guangzhou was 1.48%, among which the incidence rates were: living scatter as 1.11% living collectively as 1.66%, living in urban areas as 1.36% in rural as 2.52%. In order, the proportion of main causes of children's unintentional injuries were as follows: falls (70.54%), animal injuries (8.48%), burn and scald (5.75%), blunt force injuries (3.92%), and road traffic injuries (RTIs) (3.48%). The main body parts being injured were head and face (60.00%), wrist and hand (15.48%), knee and leg (11.70%), elbow and forearm (4.54%), shoulder and arm (2.99%). The degrees of children's unintentional injuries were as follows: mild impairment (85.35%), moderate impairment (9.12%), and severe impairment (0.57%). Places that the patients went were as follows: hospital outpatient department or emergency room (49.66%), inpatient department or ICU (2.06%), home and kindergarten (43.34%). CONCLUSION: The overall incidence rate of children's unintentional injuries under age 7 in Guangzhou was 1.48%, with main causes as fall, animal injuries, burn and scald, blunt force injuries, and RTIs. There were considerable differences of characteristics and distributions on age and areas among the patients. PMID- 22093467 TI - [A cross-sectional study on health-related knowledge and skills and its influencing factors among the Chinese college students]. AB - OBJECTIVE: To investigate the status on health-related knowledge and skills among the college students. METHODS: 5070 Chinese students from 28 universities or colleges were sampled, using the multiple-stage stratified, purposive and convenient mixed sampling method. A cross-sectional investigation on health literacy was conducted with self-designed questionnaire, and SPSS 13.0 was used to statistically analyze the data. RESULTS: The average scores on health-related related knowledge and skills among the subjects was 74.139 +/- 12.0223, with 38.4% on basic health- related literacy (scores >= 80). The rate (1.1%) of passing the margin line set for the awareness on chronic disease prevention appeared to be the lowest. And there noticed significant differences (P < 0.05) in different regions, types, and genders on the basic health-related knowledge and skills as well as on the prevalence rates of total and each dimensional health-related literacy among universities and colleges. Regions and types of universities and colleges were the main influencing factors on the levels of health-related knowledge and skills among the college students. CONCLUSION: The prevalence of basic health-related knowledge and skills was low and the prevalence rates of health-related knowledge and skills were differently distributed among student populations under study. PMID- 22093468 TI - [Acceptability and influencing factors of pre-exposure prophylaxis among men who have sex with men in Guangxi]. AB - OBJECTIVE: To study the acceptability of pre-exposure prophylaxis (PrEP) to prevent the transmission of HIV among men who have sex with men (MSM) in Guangxi, China. METHODS: Snow-balling methods were used to recruit 650 MSM in Guangxi. Questionnaires and interview were administrated to these 650 men, using a self designed questionnaire and face to face interviews to collect information on HIV related risk behaviors, knowledge and acceptability of PrEP. RESULTS: After an introduction on PrEP by interviewers, followed by as the statement-'If PrEP was effective, safe and free of charge', 597 (91.9%) of the 650 MSM claimed that they would accept it, with the main reason as the recognition of 'PrEP can decrease the risk of HIV infection'. For those who refused to use it, most of them said that were afraid of the side-effect and doubted on the effectiveness of PrEP. Data from logistic regression analysis showed that those who had found partners through friends (OR = 6.21, P = 0.020) and those who would advise his friend to use PrEP (OR = 39.32, P = 0.000) were more likely to accept PrEP. Those who thought they could protect themselves from HIV infection (OR = 0.32, P = 0.010) or not having sex with the ones who refused to use a condom (OR = 0.34, P = 0.010) were less likely to accept PrEP. CONCLUSION: Effectiveness, safety and cost seemed to be the main influential factors related to the acceptability of PrEP. Peer education might improve the acceptability of PrEP. PMID- 22093469 TI - [Surveillance on Salmonella infection in Guangdong province, 2008 - 2009]. AB - OBJECTIVE: To understand the infection of Salmonella (S.) in patients with diarrhea and outbreaks caused by Salmonella to identify the serotypes, resistance to antibiotics and PFGE types of the strains from the surveillance program in Guangdong province. METHODS: S. strains from patients with diarrhea were detected, and all the positive strains collected in routine and outbreak surveillance programs, were tested by serum agglutination, antibiotic susceptibility and PFGE. RESULTS: 71 S. strains were isolated from 1922 stool samples in 2008, with positive rate as 3.7%. 85 S. strains were isolated from 2110 stool samples in 2009, with positive rate as 4.0%. All the 156 strains were divided into 37 serotypes, with S. serotype typhimurium and enteritidis as the most common serotypes. 10 incidents of food poisoning were detected, of which 4 were caused by enteritidis and 3 by typhimurium. A suspected outbreak by enteritidis was discovered and under epidemiological investigation. The findings indicated that 2 of the 4 patients from this outbreak were infected with identical enteritidis isolates. 80% of the 229 isolates were found susceptible to cephalosporins and quinolone and 59.3% of them were multiresistant to the antibiotics. CONCLUSION: S. enteritidis and S. typhimurium were the most common serotypes that caused infectious diarrhoea and food poisoning in Guangdong province. PMID- 22093470 TI - [The spatial distribution and dynamics of human rabies cases at the county level in Henan province]. AB - OBJECTIVE: To study the spatial distribution and dynamics of human rabies cases at the county level, in Henan province to provide scientific evidence for the development of control program on rabies. METHODS: Data of human rabies cases at the county level from 2004 to 2010 in Henan province were analyzed by Poisson distribution and negative binomial distribution. Data calculation was conducted manually. RESULTS: According to the level of alpha = 0.05 being set, there were three different results appeared:the first was fitted negative binomial distribution in 2004, 2005, 2007 and 2009; the second was prioritized negative binomial distribution, but the poisson distribution could not be excluded in 2008 and 2010;the last one was fitted neither negative binomial distribution nor poisson distribution in 2006. By the clustering parameter k, the clustering degree at county level decreased from 2004 to 2008, then ascending in 2009 but descending again in 2010. The degree of clustering showed a positive correlation with the county mean cases in the prevalent counties (r = 0.807, P = 0.028). CONCLUSION: As a whole, the distribution of human rabies at county level in Henan from 2004 to 2010 showed negative binomial distribution and presented the spatial clustering. However, the degree of clustering decreased in recent years and showed that the infection resource was possibly scattered more evenly at the county level. PMID- 22093471 TI - [Burden of disease regarding paratyphoid fever A - based on the Syndromic Surveillance System on Fever]. AB - OBJECTIVE: To evaluate the burden of paratyphoid fever A in Hongta district, Yuxi city, Yunnan province from May 1, 2008 to April 30, 2009 so as to provide information for the development of comprehensive intervention measures. METHODS: Based on the Fever Syndromic Surveillance System, information as attendance rate of patients with fever, rate of patients being sampled, laboratory testing rate, sensitivity on the detection of blood culture and the rate of case reporting etc. were calculated. According to the pyramid model of food-borne disease on disease burden, the local actual incidence of paratyphoid fever A was estimated and analyzed. RESULTS: Under the Fever Syndromic Surveillance System, there were 6642 fever cases being detected, among whom 6570 cases were sampled and undergone testing, with the sampling rate as 98.92% and all the samples received laboratory testing. There were 354 positive cases of paratyphoid fever A reported, all from the Hongta district. Data showed that the attendance rate of the feverish patients was 73.53%, with the highest rate seen in whose under 10 years old (100%). Assumed that the sensitivity of paratyphoid fever blood culture was 70%, and the case reporting rate was 90%, we estimated that the annual incidence of paratyphoid fever A in Hongta was 220.33 (95%CI: 170.1 - 521.4) per 100 thousand, with 965 (95%CI: 745 - 2284) as new cases. Among all the age groups, the incidence in the age group from 15 to 44 years old was estimated to be at the highest (318.27 per 100 thousand). CONCLUSION: Hongta seemed to be an endemic region for paratyphoid fever A, with the highest incidence occurred in the age group of between 15 and 44 years old. These findings highlighted the urgent need to carry out further investigation on the risk factors and to implement targeted effective prevention and control measures. PMID- 22093473 TI - [Distribution of Staphylococcus aureus strains colonized in healthy community population and molecular epidemiological characteristics for MRSA strains]. AB - OBJECTIVE: To investigate the nasal colonization of Staphylococcus (S.) aureus strains among medical university students in Shenyang and to study the molecular epidemiological characteristics of methicillin resistant S. aureus (MRSA) strains. METHODS: Sterilized nasal swabs were used to collect nasal bacteria from both nares of the students. Nasal specimens were further identified as S. aureus strains, sensitive or resistant to methicillin through a series of tests. Molecular related methods including staphylococcal cassette chromosome mec (SCCmec) typing, pulsed- field gel electrophoresis (PFGE), coagulase isotyping and minimum inhibitory concentration (MIC) determination etc. were used to characterize the isolates. Prevalence of the panton-valentine leukocidin (pvl) genes (lukS and F-PV) among the isolates was also assessed. RESULTS: Staphylococci were found in 488 specimens from 977 participants through the surveillance program, conducted in 2009. Of the 488 specimens being tested, 364 were identified as coagulase-negative staphylococci (CoNS) and 124 as S. aureus. MRSA strain among the S. aureus isolates was accounted for 3.4%. In the surveillance program conducted in 2010, staphylococci grew in 310 specimens from 657 participants. Of the 310 specimens tested, 195 were identified as CoNS and 115 as S. aureus. The percentage of MRSA strains among the S. aureus isolates was 7.7%. In total, 239 students carried S. aureus, and the percentage of MRSA carriers among the total specimens tested in this study was 5.1%. Most of the MRSA strains could be classified into one of the five types of SCCmec elements. Type IV a SCCmec strains were most frequent seen overall (10 isolates). A total of 11 pulsotype were identified among the MRSA strains and were classified into 7 major groups (A to G) by the mutual correlations of their banding patterns. Ten MRSA strains were identified as pvl positive strains. CONCLUSION: An MRSA clone (IV a SCCmec pulsotype A) carrying pvl toxin gene was found to be prevalent in the nares of the healthy university students. PMID- 22093472 TI - [A norovirus-borne outbreak caused by contaminated bottled spring water in a school, Zhejiang province]. AB - OBJECTIVE: To study a local hospital reported acute gastroenteritis in a boarding school on its source of infection, mode of transmission and risk factors of the infection. METHODS: A suspected case was defined as who had developed diarrhea (>= 3 times/day) or vomiting among teachers or students of the school, during April 19 - 30, 2010. A confirmed case was from a probable case plus tested positive for norovirus in stool specimens by using RT-PCR. Stool specimens of cases and environmental specimens were collected for laboratory diagnosis. In a case-control study, we compared exposures to sources of bottled water, consumption of bottled water, and hygienic habits of 220 probable or confirmed cases from April 21 - 23 in the peak of the outbreak, together with another 220 controls, with frequency-matched by school grade. RESULTS: 20.3% of the 1536 students but none of the teachers developed the disease. 98.6% of the cases (n = 217) and 85.5% (n = 188) of the controls had drunk bottled water in the classroom (OR(M-H) = 12.3, 95%CI: 3.7 - 40.9). 47.9% (n = 104) of the cases and 41.5% (n = 78) of the controls had drunk unboiled bottled water in classroom (OR(M-H) = 3.8, 95%CI: 1.5 - 9.6). 47.9% (n = 104) of the cases and 48.4% (n = 91) of the controls had drunk bottled mixed water (boiled and unboiled) in the classroom (OR(M-H) = 2.8, 95%CI: 1.1 - 7.0). Stool specimens from 3 cases and one bottle of uncovered bottled water in classroom showed positive of having norovirus genotype II. Coliforms was cultured much higher rates than standard deviations in the bottled water. The factory making the bottled water was not licensed or having strict disinfection facilities. CONCLUSION: Bottled spring water contaminated by norovirus was responsible for this outbreak. PMID- 22093474 TI - [Immunogenicity and safety of DTaP-IPV//PRP-T combined vaccine in infants in China]. AB - OBJECTIVE: The aim of this study was to demonstrate the immunogenicity and safety of diphtheria, tetanus, pertussis (acellular, component), poliomyelitis (inactivated) vaccine (adsorbed) and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV//PRP-T) combined vaccine compared with commercially available DTaP (diphtheria, tetanus and pertussis), Haemophilus influenzae type b (Hib), tetanus conjugate and IPV monovalent vaccine. METHODS: Subjects were randomly divided into three groups, Group A and Group B were DTaP-IPV//PRP-T combined vaccine (PENTAXIM(TM)) vaccinated at 2, 3, 4 months of age or 3, 4, 5 months of age respectively; Group C was commercially available DTaP. Hib tetanus conjugate (Act-HIB(TM)) and IPV (IMOVAX PolioTM(TM)) vaccines vaccinated at 3, 4, 5 months of age. All groups received booster dose at 18 to 20 months of age, with antibody titers tested. Non-inferiority analysis was demonstrated in terms of seroprotection/seroconversion rates between Group A, Group B respectively and Group C. Safety information was collected after each vaccination to assess the safety of investigational vaccines. RESULTS: The non-inferiority of DTaP-IPV//PRP T combined vaccine vaccinated at 2, 3, 4 or 3, 4, 5 months of age versus DTaP, Hib tetanus conjugate and IPV vaccine was demonstrated for all vaccine antigens in both primary and booster phases in terms of seroprotection/seroconversion rates. DTaP-IPV//PRP-T combined vaccine was well tolerated. The rate of solicited/unsolicited severe adverse reactions was very low and similar to the control vaccines. CONCLUSION: DTaP-IPV//PRP-T combined vaccine was highly immunogenic with good safety profile in Chinese infants, which was comparable to the commercially available control vaccines. PMID- 22093475 TI - [Risk factors on the recurrence of ischemic stroke and the establishment of a Cox's regression model]. AB - OBJECTIVE: To investigate the risk factors and establish the Cox's regression model on the recurrence of ischemic stroke. METHODS: We retrospectively reviewed consecutive patients with ischemic stroke admitted to the Neurology Department of the Hebei United University Affiliated Hospital between January 1, 2008 and December 31, 2009. Cases had been followed since the onset of ischemic stroke. The follow-up program was finished in June 30, 2010. Kaplan-Meier methods were used to describe the recurrence rate. Monovariant and multivariate Cox's proportional hazard regression model were used to analyze the risk factors associated to the episodes of recurrence. And then, a recurrence model was set up. RESULTS: During the period of follow-up program, 79 cases were relapsed, with the recurrence rates as 12.75% in one year and 18.87% in two years. Monovariant and multivariate Cox's proportional hazard regression model showed that the independent risk factors that were associated with the recurrence appeared to be age (X1) (RR = 1.025, 95%CI: 1.003 - 1.048), history of hypertension (X2) (RR = 1.976, 95%CI: 1.014 - 3.851), history of family strokes (X3) (RR = 2.647, 95%CI: 1.175 - 5.961), total cholesterol amount (X4) (RR = 1.485, 95%CI: 1.214 - 1.817), ESRS total scores (X5) (RR = 1.327, 95%CI: 1.057 - 1.666) and progression of the disease (X6) (RR = 1.889, 95%CI: 1.123 - 3.178). Personal prognosis index (PI) of the recurrence model was as follows: PI = 0.025X1 + 0.681X2 + 0.973X3 + 0.395X4 + 0.283X5 + 0.636X6. The smaller the personal prognosis index was, the lower the recurrence risk appeared, while the bigger the personal prognosis index was, the higher the recurrence risk appeared. CONCLUSION: Age, history of hypertension, total cholesterol amount, total scores of ESRS, together with the disease progression were the independent risk factors associated with the recurrence episodes of ischemic stroke. Both recurrence model and the personal prognosis index equation were successful constructed. PMID- 22093476 TI - [Occupational and residential exposure to electric and magnetic field and its relationship on acute myeloid leukemia in adults - A Meta-analysis]. AB - OBJECTIVE: Studies had suggested that risk of leukemia might be associated with occupational or residential exposures to electromagnetic fields and varied at distance to and level of the exposure or type of occupations. Through pooled analyses, etiologic insight on the associations between exposure and disease might be explained. METHODS: We carried out a Meta-analysis based on primary data (1980 - 2010) from 9 studies related to the electric and magnetic fields exposure and acute myeloid leukemia in adults to assess whether the combined results, adjusted for potential confounding, would indicate an association between them. RESULTS: In this study the overall estimated OR value was 1.24 (95%CI: 1.11 - 1.37). The odds ratios for exposure categories of 0.1 - 0.2 uT, >= 0.2 uT, compared with < 0.1 uT, were 1.17 (95%CI: 0.98 - 1.39) and 1.51 (95%CI: 1.15 - 1.98), respectively. CONCLUSION: Through employing the alternate cut points, stratification by level of exposure or distance and the relation on different ways of exposure, there appeared consistent evidence of increased risk between acute myeloid leukemia in adults and the extremely low frequency-electromagnetic to field exposure. PMID- 22093477 TI - [Comparison on the efficacy of biphasic insulin aspart 30 and premixed human insulin 30/70 through continuous glucose monitoring system]. AB - OBJECTIVE: To compare the blood glucose levels and variability of premixed insulin aspart (BIAsp 30) with human insulin premix (BHI 30) used in a twice a day injection regimen in elderly type 2 diabetes patients. METHODS: 52 cases of inadequate glycemia controlled by oral anti-diabetic drugs were randomly divided into two groups, treated on a twice-daily regimen with BIAsp 30 (n = 26) and BHI 30 (n = 26) respectively. After achieving the target goal, a continuous glucose monitoring system (CGMS) was used to compare the blood glucose levels, blood glucose fluctuant coefficient (BGFC), postprandial glucose excursion (PPGE), and occurrence of hypoglycemia. RESULTS: BIAsp 30 was as effective as BHI 30 in control glycaemia. Detected by CGMS, there was no statistical differences in blood glucose levels among pre-three main meals, post-lunch and the mean blood glucose (MBG) (all P > 0.05). The BGFC levels were significantly lower in the BIAsp 30 group than in the BHI 30 group [(1.69 +/- 0.42) mmol/L vs. (2.07 +/- 0.51) mmol/L, t = -3.013, P < 0.01]. The blood glucose increment over breakfast, dinner and the percentage of time at hyperglycaemia (BG > 11.1 mmol/L) were lower in the BIAsp 30 group than in the BHI 30 group [(2.89 +/- 1.32) mmol/L vs. (3.83 +/- 1.18) mmol/L, t = -2.705, P < 0.01; (2.69 +/- 1.37) mmol/L vs. (3.55 +/- 1.40) mmol/L, t = -2.232, P < 0.05; (6.21 +/- 6.04)% vs. (10.01 +/- 6.80)%, t = 2.132, P < 0.05]. The frequency of hypoglycemia was lower in the BIAsp 30 group than in the BHI 30 group, but there was no statistical difference (P > 0.05). CONCLUSION: Pre-meal injection of BIAsp 30 in a twice-daily regimen could significantly improve the control of postprandial glucose level and reduce the overall glucose excursions so as to lower the risk of hypoglycaemia when compared to BHI 30. PMID- 22093478 TI - [Application of Susceptible-Infected-Recovered model in dealing with an outbreak of acute hemorrhagic conjunctivitis on one school campus]. AB - To simulate intervention measures in controlling an outbreak of acute hemorrhagic conjunctivitis on one school campus by using the Susceptible-Infected-Recovered (SIR) model, to provide evidence for preparedness and response to the epidemic. Classical SIR model was used to model the epidemic. Malthusian exponential decline method was employed to estimate the infective coefficient beta for interventions. The initial value of parameters was determined based on empirical data. The modeling was implemented using Matlab 7.1 software. Without interventions, the outbreak was expected to experience three phrases: (1) early stage (the first 5 days) in which the epidemic developed slowly and could be intervened easily; (2) rapid growing stage (6 - 15 days) in which the number of infected cases increased quickly and the epidemic could not be well controlled; and (3) medium and late stage (16 days and later) in which more than 90% of the susceptible persons were infected but the intervention measures failed to prevent the epidemic. With the implementation of interventions, the epidemic was predicted to be controlled in the early stage, under the SIR model. The simulation based on the SIR model kept an acceptable consistency with the actual development of epidemic after the implementation of intervention measures. The SIR model seemed effective in modeling interventions to the epidemic of acute hemorrhagic conjunctivitis in the schools. PMID- 22093479 TI - [Progress on using folic acid to prevent neural tube defects]. PMID- 22093480 TI - In vitro effects of RU486 on proliferation and differentiation capabilities of human bone marrow mesenchymal stromal cells. AB - Although exogenous glucocorticoids (GC) play a role in the regulation of bone marrow mesenchymal stem/stromal cells (MSCs) proliferation and differentiation, the function of endogenous GC is not well understood. The purpose of this study was to investigate the effect of the blockage of endogenous GC using RU486, an antagonist of the glucocorticoid receptor, on the in vitro proliferation and differentiation capabilities of human MSCs. We quantitatively measured cell proliferation of human MSCs after treatment with increasing concentrations of RU486. We also evaluated multiple MSC differentiation capabilities, as well as the expression of stemness and senescence genes after proliferation of these human cells in vitro in the presence of RU486 at 10(-8)M. It was observed that RU486 treatment significantly increases the proliferation of human MSCs, although the optimal dose of RU486 for this increase in proliferation differs depending on the gender of the MSC donor. This improvement in MSC proliferation with RU486 treatment was higher in MSCs from male donors than that from females. No effect of RU486 on MSC proliferation was observed in a steroid-free medium. RU486 pretreatment significantly increased the expression of mRNA for alkaline phosphatase in human MSCs and the mRNA expression of osteocalcin of these cells up-regulated earlier after their exposure to osteogenic differentiation medium. Although no statistical significance in terms of chondrogenic differentiation markers was detected, mRNA expression for aggrecan and collagen type 2 were higher in a majority of the RU486-pretreated donor MSCs than their untreated controls. No significant difference in terms of MSC adipogenic differentiation capabilities were observed after RU486 treatment. RU486 treatment up-regulated the expressions of FGF-2 and Sox-11 in human MSCs. These results indicate that blockage of endogenous GCs may be developed as a novel approach to effectively improve the proliferation and osteochondral differentiation capabilities of human MSCs for potential clinical applications. Additional studies will be required to determine the potential long-term effects of RU486 treatment on these bone marrow cells. PMID- 22093481 TI - Non-classic androgen actions in Sertoli cell membrane in whole seminiferous tubules: effects of nandrolone decanoate and catechin. AB - Studies show a mechanism of action of testosterone, nandrolone and catechin as agonists of the membrane androgen receptor. The aim of this work is to investigate the non-classical effect of androgens and catechin in Sertoli cells from immature rats. The membrane potential of Sertoli cells in whole seminiferous tubules was recorded using a standard single microelectrode technique. It was performed a topical application of testosterone (1 MUM), nandrolone (0.1, 0.5 and 1 MUM) and the flavonoid catechin (0.1, 0.5 and 1 MUM) alone and also after infusion with flutamide (1 MUM), diazoxide (100 MUM) or U73122 (1 MUM). The immature testes were incubated for 5 min in KRb with (45)Ca(2+), with or without nandrolone (1 MUM). The results were given as mean+/-SEM. The data were analyzed using ANOVA for repeated measures with Bonferroni post-test. Testosterone produces a depolarization in the membrane potential at 120 s after application. Catechin (1 MUM) and nandrolone (1 MUM) have shown a similar response to testosterone: depolarization at 120 s after the application. The same response of catechin and nandrolone was observed at different doses. The effects of testosterone, catechin and nandrolone were not affected after perfusion with flutamide. Perfusion with diazoxide and U73122 nullified the effect of nandrolone (1 MUM) and catechin (1 MUM). Nandrolone and testosterone increased (45)Ca(2+) uptake with or without flutamide within 5min. These results indicate that nandrolone and catechin act through a receptor on the plasmatic membrane, as well as testosterone, showing a non-classical pathway in Sertoli cells from immature rat testes. PMID- 22093482 TI - Estrogen receptor dependent gene expression by osteoblasts - direct, indirect, circumspect, and speculative effects. AB - Hormone activated estrogen receptors (ERs) have long been appreciated as potent mediators of gene expression in female reproductive tissues. These highly targeted responses likely evolved from more elemental roles in lower organisms, in agreement with their widespread effects in the cardiovascular, immunological, central nervous, and skeletal tissue systems. Still, despite intense investigation, the multiple and often perplexing roles of ERs retain significant attention. In the skeleton, this in part derives from apparently opposing effects by ER agonists on bone growth versus bone remodeling, and in younger versus older individuals. The complexity associated with ER activation can also derive from their interactions with other hormone and growth factor systems, and their direct and indirect effects on gene expression. We propose that part of this complexity results from essential interactions between ERs and other transcription factors, each with their own biochemical and molecular intricacies. Solving some of the many questions that persist may help to achieve better, or better directed, use of agents that can drive ER activation in focused and possibly tissue restricted ways. PMID- 22093483 TI - Rapid characterization and identification of steroidal alkaloids in Sarcococca coriacea using liquid chromatography coupled with electrospray ionization quadropole time-of-flight mass spectrometry. AB - Rapid characterization of 23 pregnane-type steroidal alkaloids was studied using a positive ion electrospray ionization quadropole time-of-flight mass spectrometry (ESI-QqTOF-MS/MS) hybrid instrument. ESI-QqTOF-MS (positive ion mode) showed the presence of the protonated molecules [M+H](+) which through low energy collision-induced dissociation tandem mass spectrometric (CID-MS/MS) analysis showed the characteristic loss of dimethylamine moiety [M+H-45](+) followed by the sequential lossess of attached substituents. Steroidal alkaloids having tigloyl or senecioyl group at C-3 produced diagnostic fragment ions at m/z 100 and 83. Our study also demonstrates the influence of unsaturation, and number and nature of substitutents on product ion abundance and fragment ions. Moreover, the generalization of the fragmentation pattern was linked with the structural features in steroidal skeleton. This strategy was successfully applied in LC-ESI QqTOF-MS/MS analysis of Sarcococca coriacea extract to investigate and characterize pregnane-type steroidal alkaloids in complex mixture. PMID- 22093484 TI - VDR dependent and independent effects of 1,25-dihydroxyvitamin D3 on nitric oxide production by osteoblasts. AB - 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) strongly mediates bone mass. Mechanical stimulation also affects bone mass, partly via enhancing nitric oxide (NO) production by osteoblasts. We aimed to determine whether 1,25(OH)(2)D(3) affects NO production by osteoblasts in the presence or absence of mechanical stimulation. We hypothesised that 1,25(OH)(2)D(3) stimulates NO production via nuclear actions of the vitamin D receptor (VDR), which requires hours of incubation with 1,25(OH)(2)D(3) to occur. MC3T3-E1 osteoblasts and long-bone osteoblasts of adult wildtype and VDR(-/-) mice were pre-incubated for 24h with or without 1,25(OH)(2)D(3) (10(-13)-10(-9)M), followed by 30 min pulsating fluid flow (PFF; 0.7+/-0.3 Pa, 5 Hz) or static culture with or without 1,25(OH)(2)D(3). NO production and NO synthase (NOS) expression were quantified. 10(-11)M 1,25(OH)(2)D(3) for 24h, but not 30 min, stimulated NO production by MC3T3-E1 osteoblasts (eightfold). 1,25(OH)(2)D(3) for 24h increased inducible-NOS gene expression (twofold), suggesting that 1,25(OH)(2)D(3) stimulated NO production via activation of NOS gene transcription. PFF rapidly increased NO production by MC3T3-E1 osteoblasts, wildtype osteoblasts, and VDR(-/-) osteoblasts. This PFF effect was abolished after incubation with 1,25(OH)(2)D(3) for 24h, or during PFF only. Our results suggest that 1,25(OH)(2)D(3) stimulates inducible-NOS expression and NO production by osteoblasts in the absence of mechanical stimulation, likely via genomic VDR action. In contrast, 1,25(OH)(2)D(3) may affect mechanical loading-induced NO production independent of genomic VDR action, since 1,25(OH)(2)D(3) diminished PFF-induced NO production in VDR(-/-) bone cells. In conclusion, 1,25(OH)(2)D(3) and mechanical loading interact at the level of mechanotransduction, whereby 1,25(OH)(2)D(3) seems to act independently of VDR genomic mechanism. PMID- 22093485 TI - Effect of intensive counselling on the quality of dietary fats in pregnant women at high risk of gestational diabetes mellitus. AB - As part of a feasibility study to prevent gestational diabetes mellitus (GDM), we evaluated the effect of an intensive dietary therapy on quality of diet, weight gain and birth weight in women at high risk of GDM. Women with risk factors for GDM (n 54) were randomly assigned from April 2005 to May 2006 to a lifestyle intervention group (n 27) including dietary advice six times during pregnancy or to a close follow-up group (n 27) in a community-based setting in Finland. Dietary intake was recorded three times during pregnancy using 4 d food records. The main outcome was the incidence of GDM. The secondary outcomes were the changes in nutrient intake, weight gain and birth weight. Overall, seventeen (65 %) women in the intervention group and eighteen (69 %) women in the close follow up group returned all three food records. PUFA intake increased (P = 0.008) during pregnancy in the intervention as compared to the close follow-up group. There were no clear differences in the changes of saturated fat or fibre intake between the groups. Intensive dietary education resulted in a somewhat lower weight gain during pregnancy (P = 0.062) and higher birth weights of the infants (P = 0.047) without an effect on macrosomia as compared to the close follow-up group. Individualised counselling by a clinical nutritionist as part of a lifestyle intervention improved the quality of dietary fat intake in pregnant women at high risk of GDM. PMID- 22093486 TI - Effect of delaying surgery on radical prostatectomy outcomes: a contemporary analysis. AB - Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? For patients electing surgical treatment, the question of the effect of surgical delay on clinical outcomes in prostate cancer is controversial. In this study we examined the effect of delay from diagnosis to surgery on outcomes in men with localized prostate cancer and found no association between time to surgery and risk of biochemical recurrence, even for patients with longer delays and high-risk disease. Men with localized prostate cancer can be reassured that reasonable delays in treatment will not influence disease outcomes. OBJECTIVE: * To examine the effect of time from last positive biopsy to surgery on clinical outcomes in men with localized prostate cancer undergoing radical prostatectomy (RP). PATIENTS AND METHODS: * We conducted a retrospective review of 2739 men who underwent RP between 1990 and 2009 at our institution. * Clinical and pathological features were compared between men undergoing RP <= 60, 61-90 and >90 days from the time of prostate biopsy. * A Cox proportional hazards model was used to analyse the association between clinical features and surgical delay with biochemical progression. Biochemical recurrence (BCR)-free rates were assessed using the Kaplan-Meier method. RESULTS: * Of the 1568 men meeting the inclusion criteria, 1098 (70%), 303 (19.3%) and 167 (10.7%) had a delay of <= 60, 61-90 and >90 days, respectively, between biopsy and RP. A delay of >60 days was not associated with adverse pathological findings at surgery. * The 5-year survival rate was similar among the three groups (78-85%, P= 0.11). * In a multivariate Cox model, men with higher PSA levels, clinical stages, Gleason sums, and those of African-American race were all at higher risk for developing BCR. * A delay to surgery of >60 days was not associated with worse biochemical outcomes in a univariate and multivariate model. CONCLUSIONS: * A delay of >60 days is not associated with adverse pathological outcomes in men with localized prostate cancer, nor does it correlate with worse BCR-free survival. * Patients can be assured that delaying treatment while considering therapeutic options will not adversely affect their outcomes. PMID- 22093487 TI - How plants cope with temperature stress. AB - A cold night can follow a hot day, and because they cannot move, plants subjected to such temperature fluctuations must acclimate on the basis mainly of pre existing proteins. Zhang et al. report in a paper in BMC Plant Biology, however, that heat-induced cell death results from transcriptional activation of a kinase related to disease resistance factors and leading to a localized hypersensitive response. This specialized response reflects the failure of adaptations that normally enable plants to survive over a remarkable temperature range, by mechanisms that are not fully understood. PMID- 22093488 TI - The impact of buprenorphine on treatment of opioid dependence in a Medicaid population: recent service utilization trends in the use of buprenorphine and methadone. AB - BACKGROUND: Buprenorphine provides an important option for individuals with opioid dependence who are unwilling or unable to attend a licensed methadone opioid agonist treatment program to receive opioid agonist therapy (OAT). Little empirical information is available, however, about the extent to which buprenorphine has increased the percentage of opioid dependent individuals receiving OAT, nor to what extent buprenorphine is being used in office based settings. METHODS: Using administrative data from the largest Medicaid managed behavioral health organization in a large mid-Atlantic state, we used multivariate regression to examine rates and predictors of opioid agonist use and treatment setting for 14,386 new opioid dependence treatment episodes during 2007 2009. RESULTS: Despite an increase in the use of buprenorphine, the percentage of new treatment episodes involving OAT is unchanged due to a decrease in the percentage of episodes involving methadone. Use of buprenorphine was significantly more common in rural communities, and 64% of buprenorphine use was in office-based settings. CONCLUSION: Buprenorphine use has increased in recent years, with the greatest use in rural communities and in office based settings. However, the percentage of new opioid dependence treatment episodes involving an opioid agonist is unchanged, suggesting the need for further efforts to increase buprenorphine use among urban populations. PMID- 22093489 TI - Demographic history, genetic structure and gene flow in a steppe-associated raptor species. AB - BACKGROUND: Environmental preferences and past climatic changes may determine the length of time during which a species range has contracted or expanded from refugia, thereby influencing levels of genetic diversification. Connectivity among populations of steppe-associated taxa might have been maximal during the long glacial periods, and interrupted only during the shorter interglacial phases, potentially resulting in low levels of genetic differentiation among populations. We investigated this hypothesis by exploring patterns of genetic diversity, past demography and gene flow in a raptor species characteristic of steppes, the Montagu's harrier (Circus pygargus), using mitochondrial DNA data from 13 breeding populations and two wintering populations. RESULTS: Consistent with our hypothesis, Montagu's harrier has relatively low genetic variation at the mitochondrial DNA. The highest levels of genetic diversity were found in coastal Spain, France and central Asia. These areas, which were open landscapes during the Holocene, may have acted as refugia when most of the European continent was covered by forests. We found significant genetic differentiation between two population groups, at the SW and NE parts of the species' range. Two events of past population growth were detected, and occurred ca. 7500-5500 and ca. 3500-1000 years BP in the SW and NE part of the range respectively. These events were likely associated with vegetation shifts caused by climate and human induced changes during the Holocene. CONCLUSIONS: The relative genetic homogeneity observed across populations of this steppe raptor may be explained by a short isolation time, relatively recent population expansions and a relaxed philopatry. We highlight the importance of considering the consequence of isolation and colonization processes in order to better understand the evolutionary history of steppe species. PMID- 22093490 TI - Endometriosis of the round ligament of the uterus. AB - STUDY OBJECTIVE: To demonstrate the prevalence of endometriosis in the intrapelvic portion of the round ligaments of the uterus (RLUs) and to propose criteria for their excision. DESIGN: Retrospective case series analysis of women undergoing laparoscopy for the treatment of deep infiltrating endometriosis (Canadian Task Force classification II-3). SETTING: Tertiary referral hospital. PATIENTS: We evaluated 174 patients who underwent laparoscopy for the treatment of deep infiltrating endometriosis (DIE) between April 2006 and May 2009. INTERVENTIONS: All patients underwent laparoscopy for the treatment of DIE and had their RLUs removed when there was shortening, deviation, or thickening. After removal, the RLUs were sent for histopathologic analysis to verify the presence or absence of endometriosis. MEASUREMENTS AND MAIN RESULTS: The prevalence of endometriosis in the RLUs and the association between the macroscopic alterations and the anatomic pathology results were determined. After the identification of macroscopic alterations, 1 or both RLUs (for a total of 42) were removed from 27 of the 174 patients who underwent laparoscopy. The positive predictive value (PPV) of the macroscopic criteria proposed for endometriosis of the RLU was 83.3% (95% confidence interval [CI] = 72.1%-94.5%), with 35 positive RLUs out of the 42 that were excised. The prevalence of endometriosis of the RLU was 13.8% (95% CI = 8.7%-18.9%), with 24 patients having a positive histopathologic examination result for endometriosis. CONCLUSIONS: The prevalence of RLU endometriosis in patients with DIE was 13.8%, which emphasizes that a rigorous evaluation of this structure must be part of the routine surgical treatment of patients with endometriosis. PMID- 22093491 TI - Do schools differ in suicide risk? The influence of school and neighbourhood on attempted suicide, suicidal ideation and self-harm among secondary school pupils. AB - BACKGROUND: Rates of suicide and poor mental health are high in environments (neighbourhoods and institutions) where individuals have only weak social ties, feel socially disconnected and experience anomie - a mismatch between individual and community norms and values. Young people spend much of their time within the school environment, but the influence of school context (school connectedness, ethos and contextual factors such as school size or denomination) on suicide-risk is understudied. Our aim is to explore if school context is associated with rates of attempted suicide and suicide-risk at age 15 and self-harm at age 19, adjusting for confounders. METHODS: A longitudinal school-based survey of 1698 young people surveyed when aged 11, (primary school), 15 (secondary school) and in early adulthood (age 19). Participants provided data about attempted suicide and suicide-risk at age 15 and deliberate self-harm at 19. In addition, data were collected about mental health at age 11, social background (gender, religion, etc.), and at age 15, perception of local area (e.g. neighbourhood cohesion, safety/civility and facilities), school connectedness (school engagement, involvement, etc.) and school context (size, denomination, etc.). A dummy variable was created indicating a religious 'mismatch', where pupils held a different faith from their school denomination. Data were analysed using multilevel logistic regression. RESULTS: After adjustment for confounders, pupils attempted suicide, suicide-risk and self-harm were all more likely among pupils with low school engagement (15-18% increase in odds for each SD change in engagement). While holding Catholic religious beliefs was protective, attending a Catholic school was a risk factor for suicidal behaviours. This pattern was explained by religious 'mismatch': pupils of a different religion from their school were approximately 2-4 times more likely to attempt suicide, be a suicide risk or self-harm. CONCLUSIONS: With several caveats, we found support for the importance of school context for suicidality and self-harm. School policies promoting school connectedness are uncontroversial. Devising a policy to reduce risks to pupils holding a different faith from that of their school may be more problematic. PMID- 22093493 TI - Inhibin B for assessment of ovarian reserve after laparoscopic treatment of ovarian endometriomas. PMID- 22093492 TI - Severe fetal ischemic complications caused by second trimester amniotic fluid embolism. PMID- 22093494 TI - Hemoperitoneum assessment in ectopic pregnancy. AB - OBJECTIVE: To identify routine clinical, ultrasound, and biologic criteria to assess the volume of hemoperitoneum in women with ectopic pregnancy (EP). METHODS: Except for patients with hemodynamic shock, all women assigned to surgical laparoscopic treatment for confirmed EP at Poissy Saint Germain en Laye Hospital between January 2004 and December 2007 were included in the study. The patients underwent abdominal and digital pelvic examination, and standardized ultrasonography. Ordered logistic regression analysis was performed to select criteria associated with an increase in hemoperitoneum. The diagnostic accuracy of each variable was then calculated for different hemoperitoneum cut-off values. RESULTS: The study included 215 patients. Pelvic pain of 4 or above on a numeric rating scale (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.3-4.1), abdominal guarding or rebound tenderness (OR, 4.6; 95% CI, 2.0-10.8), hemoglobin under 10 g/dL (OR, 12.2; 95% CI, 4.2-35.8), presence of fluid at transvaginal ultrasound (OR, 3.6; 95% CI, 1.4-9.2), and fluid in Morison pouch at abdominal ultrasound (OR, 5.6; 95% CI, 2.0-15.9) were found to be independently associated with hemoperitoneum. CONCLUSION: Both clinical examination and standardized ultrasonography were found to be useful for accurate evaluation of hemoperitoneum in patients presenting with EP. PMID- 22093495 TI - Fertility sparing therapy for metastatic gestational trophoblastic disease in young patients. PMID- 22093496 TI - Laparoscopic hysterectomy versus abdominal hysterectomy for severe pelvic endometriosis. AB - OBJECTIVE: To compare the surgical outcomes of laparoscopic hysterectomy (LH) versus abdominal hysterectomy (AH) in patients with severe pelvic endometriosis. METHODS: A retrospective review of patients undergoing hysterectomy for endometriosis was conducted between January 2002 and December 2007. A total of 503 patients had severe pelvic endometriosis; of these, 115 patients underwent LH and 388 patients underwent AH. Surgical outcomes-including operative time, blood loss, length of hospital stay, and need for blood transfusion-were analyzed and compared between the 2 treatment groups. RESULTS: Operative time was significantly longer for LH than for AH (185.1 +/- 48.7 minutes and 139.9 +/- 52.4 minutes, respectively; P<0.001). However, estimated volume of blood loss, length of hospital stay, and complication rates were significantly less for patients in the LH group than for those in the AH group (302.6 +/- 255.1 mL versus 760.9 +/- 633.2 mL [P<0.001]; 3.5 +/- 1.1 days versus 6.4 +/- 3.0 days [P<0.001]; and 18.3% versus 49.0% [P<0.001], respectively). CONCLUSION: Compared with AH, LH was associated with fewer complications. LH should, therefore, be the preferred surgical option for women with severe pelvic endometriosis who require a hysterectomy. PMID- 22093497 TI - The optimal cutoff serum level of human chorionic gonadotropin for efficacy of methotrexate treatment in women with extrauterine pregnancy. AB - OBJECTIVE: To evaluate the efficacy of methotrexate treatment for extrauterine pregnancy and define criteria for prediction of success. METHODS: Of 829 patients with an ectopic pregnancy admitted to E. Wolfson Medical Center, Holon, Israel, from January 1997 through December 2009, 238 had asymptomatic tubal pregnancies and increasing serum beta-human chorionic gonadotropin (betahCG) levels. These patients were treated with a single intramuscular injection of 50mg of methotrexate (MTX) per square meter of body surface. Success was defined as undetectable betahCG levels without the need for a surgical intervention. RESULTS: The groups of patients successfully treated (n=167 [70%]) and unsuccessfully treated (n=71 [30%]) were compared. They were similar regarding age and gravidity. The initial serum betahCG level was significantly higher in the latter group than in the former (3798 mIU/mL vs. 1601 mIU/mL, P<0.01). The success rate was 88% when initial betahCG levels were less than 1000 mIU/mL, 71% when they were between 1000 and 2000 mIU/mL, and only 59% when they were between 2000 and 3000 mIU/mL. CONCLUSION: Methotrexate treatment is a safe and effective alternative to surgery. However, patients with initial betahCG levels higher than 2000 mIU/mL should only be offered the surgical approach. PMID- 22093498 TI - Perinatal outcomes and congenital abnormalities in the newborns of women affected by the 2009 pandemic influenza A (H1N1) in Beijing, China. AB - OBJECTIVE: To investigate the pregnancy complications, perinatal outcomes, and congenital abnormalities (CAs) that occurred in Beijing, China, when pregnant women became infected with the 2009 pandemic influenza A (H1N1) (H1N1 pdm). METHODS: Pregnancy complications, perinatal outcomes, and CAs were compared among 3 groups of pregnant women. The 23 women in group 1 were confirmed to harbor viral RNA; the 23 in group 2 had serum levels of virus-specific antibodies against H1N1 pdm, meaning that they were suspected of being infected with the virus; and the 93 in group 3 had no detectable virus-specific antibodies. RESULTS: Perinatal outcomes and pregnancy complications were not significantly different in groups 1 and 3. Higher percentages of stillbirths (12.0%) and placental disorders (13.0%) were observed in group 2 than in group 3. Many women in group 2 (62.5%) experienced symptoms of having a cold during pregnancy and most took no medication. Two cases of CA occurred in group 1, in the offspring of women infected in the second trimester. CONCLUSION: When left untreated, infection with the 2009 H1N1 pdm virus during pregnancy appears to have increased fetal mortality and morbidity. Because CAs are traumatic for all concerned, their possible association with the virus should be further evaluated. PMID- 22093499 TI - Influence of HIV infection on women's resumption of sexual intercourse and use of contraception in the postpartum period in rural Uganda. PMID- 22093500 TI - Obstetrician-gynecologists' knowledge of and attitudes toward medical abortion in Guatemala. AB - OBJECTIVE: To characterize the legal and clinical knowledge of Guatemalan obstetrician-gynecologists (OB/GYNs) regarding medical abortion and to determine factors associated with approval of its use for specific indications. METHODS: A trained interviewer administered a multiple-choice survey to 172 private-practice OB/GYNs across Guatemala. Univariate, bivariate, and multivariate analyses characterized medical abortion opinion and knowledge, and logistic regression identified influential factors. RESULTS: 73% of OB/GYNs knew that abortion is legally permitted when the woman's life is at risk. Although 92% knew that misoprostol can be used to induce abortion, only 35% knew the WHO-recommended dosage. Only 25% knew of mifepristone. Compared with older OB/GYNs, those under 40 years of age were 7 times more likely, and 40-49 year olds were twice as likely to approve of medical abortion for fetal death and severe eclampsia with fetal death, respectively. CONCLUSION: Current indications for abortion under Guatemalan law, as well as OB/GYN practices and beliefs regarding medical abortion, are hindering women's access to safe medical abortion and, therefore, potential reductions in maternal morbidity and mortality. Future research should aim to identify whether and why Guatemalan OB/GYNs are unfamiliar with these drugs, prefer to use other methods, or are completely against abortion. PMID- 22093501 TI - Safety and efficacy of antiplatelet and antithrombotic therapy in acute coronary syndrome patients with chronic kidney disease. AB - Chronic kidney disease (CKD) is prevalent and affects an ever-increasing proportion of patients presenting with acute coronary syndrome (ACS). Patients with CKD have a higher risk of ACS and significantly higher mortality, and are also predisposed to increased bleeding complications. Antiplatelet and antithrombotic drugs form the bedrock of management of patients with ACS. Most randomized trials of these drugs exclude patients with CKD, and current guidelines for management of these patients are largely based on these trials. We aim to review the safety and efficacy of these drugs in patients with CKD presenting with ACS. PMID- 22093503 TI - Myocardial expression levels of micro-ribonucleic acids in patients with left ventricular assist devices signature of myocardial recovery, signature of reverse remodeling, or signature with no name? PMID- 22093502 TI - A micro-ribonucleic acid signature associated with recovery from assist device support in 2 groups of patients with severe heart failure. AB - OBJECTIVES: This study was conducted to test the hypothesis that cardiac micro ribonucleic acid (miR) profiling in severe heart failure patients at the time of ventricular assist device (VAD) placement would differentiate those who remained VAD-dependent from those with subsequent left ventricular (LV) recovery. BACKGROUND: The relationship of myocardial miR expression to ventricular recovery is unknown. METHODS: We studied 28 patients with nonischemic cardiomyopathy requiring VAD support consisting of test and validation cohorts from 2 institutions: 14 with subsequent LV recovery and VAD removal and 14 clinically matched VAD-dependent patients. Apical core myocardium was studied for expression of 376 miRs by polymerase chain reaction (PCR) array and real-time-PCR methods. Samples from 7 nonfailing hearts were used in confirmatory studies. RESULTS: By PCR array, 10 miRs were differentially expressed between LV recovery and VAD dependent patients in the test cohort. The real-time PCR confirmed lower expression in LV recovery patients for 4 miRs (15b, -1.5-fold; 23a, -2.2-fold; 26a, -1.4-fold; and 195, -1.8-fold; all p < 0.04 vs. VAD dependent). The validation cohort similarly showed lower miRs expression in LV recovery patients (23a, -1.8-fold; and 195, -1.5-fold; both p < 0.03). Furthermore, miR 23a and 195 expression in nonfailing hearts was similar to LV recovery patients (both p < 0.04 vs. VAD dependent). The LV recovery patients also had significantly smaller cardiomyocytes by quantitative histology in both cohorts. CONCLUSIONS: Lower cardiac expression of miRs 23a and 195 and smaller cardiomyocyte size at the time of VAD placement were associated with subsequent LV functional recovery. Differential expression of miRs at VAD placement may provide markers to assess recovery potential. PMID- 22093504 TI - Implantable cardioverter-defibrillator patients who are upgraded and respond to cardiac resynchronization therapy have less ventricular arrhythmias compared with nonresponders. AB - OBJECTIVES: The purpose of this study was to evaluate the impact of upgrading implantable cardioverter-defibrillator (ICD) therapy to cardiac resynchronization therapy (CRT) combined with defibrillator (CRT-D) on the occurrence of ventricular arrhythmia (VA) and appropriate ICD therapies. BACKGROUND: CRT has been shown to improve left ventricular (LV) systolic function and induce reverse LV remodeling. In addition, it has been hypothesized that CRT may reduce the incidence of VA. METHODS: Heart failure patients receiving an upgrade from ICD to CRT-D were evaluated. Patients were considered responders to CRT if LV end systolic volume reduced >=15% at 6 months of follow-up. Episodes of VA, triggering device therapy (anti-tachycardia pacing and shocks) were recorded before and after upgrade for the overall population. In addition, these outcomes were compared between CRT responders and nonresponders during the follow-up period after CRT response was assessed. RESULTS: One hundred fifteen patients (93 males [81%], age 65 +/- 12 years) were evaluated during a mean follow-up of 54 +/ 34 months before CRT-D upgrade and 37 +/- 27 months after upgrade. In CRT responders (n = 70), the frequency of VA requiring appropriate device therapy demonstrated a trend toward a decrease from 0.51 +/- 0.79 to 0.30 +/- 0.59 per patient per year after CRT-D upgrade (p = 0.052). In CRT nonresponders (n = 45), the frequency of VA requiring appropriate device therapy significantly increased from 0.40 +/- 0.69 to 1.21 +/- 2.53 per patient per year after CRT-D upgrade (p = 0.014). CONCLUSIONS: After upgrade from ICD to CRT-D, nonresponders to CRT showed a significant increase in VA burden requiring appropriate device therapy. PMID- 22093505 TI - New electrocardiographic criteria for discriminating between Brugada types 2 and 3 patterns and incomplete right bundle branch block. AB - OBJECTIVES: The aim of this study was to evaluate new electrocardiographic (ECG) criteria for discriminating between incomplete right bundle branch block (RBBB) and the Brugada types 2 and 3 ECG patterns. BACKGROUND: Brugada syndrome can manifest as either type 2 or type 3 pattern. The latter should be distinguished from incomplete RBBB, present in 3% of the population. METHODS: Thirty-eight patients with either type 2 or type 3 Brugada pattern that were referred for an antiarrhythmic drug challenge (AAD) were included. Before AAD, 2 angles were measured from ECG leads V(1) and/or V(2) showing incomplete RBBB: 1) alpha, the angle between a vertical line and the downslope of the r'-wave, and 2) beta, the angle between the upslope of the S-wave and the downslope of the r'-wave. Baseline angle values, alone or combined with QRS duration, were compared between patients with negative and positive results on AAD. Receiver-operating characteristic curves were constructed to identify optimal discriminative cutoff values. RESULTS: The mean beta angle was significantly smaller in the 14 patients with negative results on AAD compared to the 24 patients with positive results on AAD (36 +/- 20 degrees vs. 62 +/- 20 degrees , p < 0.01). Its optimal cutoff value was 58 degrees , which yielded a positive predictive value of 73% and a negative predictive value of 87% for conversion to type 1 pattern on AAD; alpha was slightly less sensitive and specific compared with beta. When the angles were combined with QRS duration, it tended to improve discrimination. CONCLUSIONS: In patients with suspected Brugada syndrome, simple ECG criteria can enable discrimination between incomplete RBBB and types 2 and 3 Brugada patterns. PMID- 22093506 TI - On the intriguing phenotypic manifestations of Brugada syndrome and the diagnostic value of the electrocardiogram. PMID- 22093507 TI - Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. AB - OBJECTIVES: We investigated the temporal pattern and predictive value (alone and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein [L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated acute kidney injury (AKI). BACKGROUND: Serum creatinine (S(Cr)) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes. METHODS: Data from 220 pediatric patients were analyzed. Urine samples were obtained before and at intervals after CPB initiation. AKI was defined as a >=50% increase in S(Cr) from baseline within 48 h after CPB. The temporal pattern of biomarker elevation was established, and biomarker elevations were correlated with AKI severity and clinical outcomes. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement, and integrated discrimination improvement. RESULTS: AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18 and L-FABP increased at 6 h, and KIM 1 increased at 12 h. Biomarker elevations were correlated with AKI severity and clinical outcomes and improved AKI prediction above a clinical model. At 2 h, addition of NGAL increased the AUC from 0.74 to 0.85 (p < 0.0001). At 6 h, NGAL, IL-18, and L-FABP each improved the AUC from 0.72 to 0.91, 0.84, and 0.77, respectively (all p < 0.05). The added predictive ability of the biomarkers was supported by net reclassification improvement and integrated discrimination improvement. Biomarker combinations further improved AKI prediction. CONCLUSIONS: Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and are correlated with disease severity and clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may help establish the timing of injury and allow earlier intervention in AKI. PMID- 22093508 TI - Can novel biomarkers complement best possible clinical assessment for early acute kidney injury diagnosis? PMID- 22093509 TI - Long-term survival in patients with resting obstructive hypertrophic cardiomyopathy comparison of conservative versus invasive treatment. AB - OBJECTIVES: The aim of this study was to compare the survival of patients with hypertrophic cardiomyopathy (HCM) and resting left ventricular outflow tract (LVOT) obstruction managed with an invasive versus a conservative strategy. BACKGROUND: In patients with resting obstructive HCM, clinical benefit can be achieved after invasive septal reduction therapy. However, it remains controversial whether invasive treatment improves long-term survival. METHODS: We studied a consecutive cohort of 649 patients with resting obstructive HCM. Total and HCM-related mortality were compared in 246 patients who were conservatively managed with 403 patients who were invasively managed by surgical myectomy, septal ethanol ablation, or dual-chamber pacing. RESULTS: Multivariable analyses (with invasive therapy treated as a time-dependent covariate) showed that an invasive intervention was a significant determinant of overall mortality (hazard ratio: 0.6, 95% confidence interval: 0.4 to 0.97, p = 0.04). Overall survival rates were greater in the invasive (99.2% 1-year, 95.7% 5-year, and 87.8% 10-year survival) than in the conservative (97.3% 1-year, 91.1% 5-year, and 75.8% 10-year survival, p = 0.008) cohort. However, invasive therapy was not found to be a significant independent predictor of HCM-related mortality (hazard ratio: 0.7, 95% confidence interval: 0.4 to 1.3, p = 0.3). The HCM-related survival was 99.5% (1 year), 96.3% (5 years), and 90.2% (10 years) in the invasive cohort, and 97.8% (1 year), 94.6% (5 years), and 86.9% (10 years) in the conservative cohort (p = 0.3). CONCLUSIONS: Patients treated invasively have an overall survival advantage compared with conservatively treated patients, with the latter group more likely to die from noncardiac causes. The HCM-related mortality is similar, regardless of a conservative versus invasive strategy. PMID- 22093510 TI - Alcohol septal ablation for the treatment of hypertrophic obstructive cardiomyopathy. A multicenter North American registry. AB - OBJECTIVES: The purpose of the study is to identify the predictors of clinical outcome (mortality and survival without repeat septal reduction procedures) of alcohol septal ablation for the treatment of patients with hypertrophic obstructive cardiomyopathy. BACKGROUND: Alcohol septal ablation is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe outflow tract obstruction. The existing literature is limited to single-center results, and predictors of clinical outcome after ablation have not been determined. Registry results can add important data. METHODS: Hypertrophic obstructive cardiomyopathy patients (N = 874) who underwent alcohol septal ablation were enrolled. The majority (64%) had severe obstruction at rest, and the remaining had provocable obstruction. Before ablation, patients had severe dyspnea (New York Heart Association [NYHA] functional class III or IV: 78%) and/or severe angina (Canadian Cardiovascular Society angina class III or IV: 43%). RESULTS: Significant improvement (p < 0.01) occurred after ablation (~5% in NYHA functional classes III and IV, and 8 patients in Canadian Cardiovascular Society angina class III). There were 81 deaths, and survival estimates at 1, 5, and 9 years were 97%, 86%, and 74%, respectively. Left anterior descending artery dissections occurred in 8 patients and arrhythmias in 133 patients. A lower ejection fraction at baseline, a smaller number of septal arteries injected with ethanol, a larger number of ablation procedures per patient, a higher septal thickness post-ablation, and the use beta-blockers post ablation predicted mortality. CONCLUSIONS: Variables that predict mortality after ablation, include baseline ejection fraction and NYHA functional class, the number of septal arteries injected with ethanol, post-ablation septal thickness, beta-blocker use, and the number of ablation procedures. PMID- 22093511 TI - The role of alcohol septal ablation in the treatment of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. PMID- 22093512 TI - Inhibition of c-Src tyrosine kinase prevents angiotensin II-mediated connexin-43 remodeling and sudden cardiac death. AB - OBJECTIVES: The aim of this study was to test whether c-Src tyrosine kinase mediates connexin-43 (Cx43) reduction and sudden cardiac death in a transgenic mouse model of cardiac-restricted overexpression of angiotensin-converting enzyme (ACE8/8 mice). BACKGROUND: Renin-angiotensin system activation is associated with an increased risk for arrhythmia and sudden cardiac death, but the mechanism is not well understood. The up-regulation of c-Src by angiotensin II may result in the reduction of Cx43, which impairs gap junction function and provides a substrate for arrhythmia. METHODS: Wild-type and ACE8/8 mice with and without treatment with the c-Src inhibitor 1-(1,1-dimethylethyl)-1-(4-methylphenyl)-1H pyrazolo[3,4-d]pyrimidin-4-amine (PP1) were studied. Telemetry monitoring, in vivo electrophysiologic studies, Western blot analyses for total and phosphorylated c-Src and Cx43, immunohistochemistry staining for Cx43, and functional assessment of Cx43 with fluorescent dye diffusion were performed. RESULTS: The majority of the arrhythmic deaths resulted from ventricular tachycardia degenerating to ventricular fibrillation (83%). Levels of total and phosphorylated c-Src were increased and Cx43 reduced in ACE8/8 mice. PP1 reduced total and phosphorylated c-Src levels, increased Cx43 level by 2.1-fold (p < 0.005), increased Cx43 at the gap junctions (immunostaining), improved gap junctional communication (dye spread), and reduced ventricular tachycardia inducibility and sudden cardiac death. The survival rate increased from 11% to 86% with 4 weeks of PP1 treatment (p < 0.005). Treatment with an inactive analog did not change survival or Cx43 levels. CONCLUSIONS: Renin-angiotensin system activation is associated with c-Src up-regulation, Cx43 loss, reduced myocyte coupling, and arrhythmic sudden death, which can be prevented by c-Src inhibition. This suggests that an increase in c-Src activity may help mediate renin-angiotensin system-induced arrhythmias and that c-Src inhibitors might exert antiarrhythmic activity. PMID- 22093513 TI - Is c-Src tyrosine kinase a new target for antiarrhythmic drug therapy? PMID- 22093514 TI - The year in non-ST-segment elevation acute coronary syndrome. PMID- 22093515 TI - Isolated left ventricular apical hypoplasia evaluated by cardiovascular magnetic resonance and gadolinium enhancement techniques. PMID- 22093516 TI - Thrombus entrapment by a novel mesh-covered stent in ST-segment elevation myocardial infarction. PMID- 22093517 TI - Murine typhus in the homeless. AB - Homeless populations are particularly exposed to many vector-borne diseases because of their poor living conditions. We tested sera from 299 homeless people recruited in 2010 and 2011 in Marseilles, France for antibodies to Rickettsia typhi by microimmunofluorescence using a titer of 1:25 as a cut-off titer, and we confirmed the results by Western blot and cross-adsorption studies. Sixty-three persons (22%) had antibodies against R. typhi. The murine typhus seroprevalence rates have significantly increased in homeless populations between the 2000-2003 and 2010-2011 periods. These findings indicate that the homeless are increasingly exposed to flea-borne murine typhus in Marseilles. One might suggest that multiple strikes of sanitation workers resulting in the increase of waste and construction sites combined with the poor living conditions of the homeless expose this population to rodents and their fleas. Further annual studies are necessary to follow rodent-associated diseases among homeless people in Marseille. PMID- 22093519 TI - Russell Palmer: forgotten champion: how victory in Holland launched the British Columbia renal failure program. PMID- 22093520 TI - Reflections on Russell Palmer. PMID- 22093521 TI - Massive, painful tumoral calcinosis in a long-term hemodialysis patient. AB - In chronic dialysis patients, ectopic, extraosseous calcifications can cause significant morbidity. Uremic tumoral calcinosis is an uncommon and severe complication of dialysis therapy. It is defined as deposition of dense nodular calcium-containing masses surrounding the large joints of the body, generally associated with the presence of high serum calcium-and-phosphorus product. We describe a 69-year-old woman submitted to long-term chronic hemodialysis that developed painful, bilateral hip tumors. Radiographic investigation showed extensive periarticular calcifications, and a bone biopsy was suggestive of adynamic bone disease and contained substantial amounts of aluminum. The lesions were surgically excised, and the histological analysis demonstrated amorphous, calcified material associated with densely collagenized connective tissue. PMID- 22093522 TI - Theoretical study of carbazole-triphenylamine-based dyes for dye-sensitized solar cells. AB - Three carbazole-triphenylamine-based dyes (D1, D2, D3) are designed. The geometries, electronic structures, and electronic absorption spectra of these dyes are studied by DFT and TD-DFT. The calculated geometries indicate that these dyes are all noncoplanar, which can help to inhibit the close intermolecular pi pi aggregation effectively. The LUMO and HOMO energy levels of these dyes can be ensuring positive effect on the process of electron injection and dye regeneration. The trend of the calculated HOMO-LUMO gaps nicely compares with the spectral data. The calculated results of these dyes demonstrate that these dyes can be used as potential sensitizers for TiO(2) nanocrystalline solar cells. PMID- 22093523 TI - DNA binding, DNA cleavage and cytotoxicity studies of a new water soluble copper(II) complex: the effect of ligand shape on the mode of binding. AB - The interaction of native calf thymus DNA (CT-DNA) with [Cu(ph(2)phen)(phen dione)Cl]Cl was studied at physiological pH by spectrophotometric, spectrofluorometric, circular dichroism, and viscometric techniques. Considerable hypochromicity and red shift are observed in the UV absorption band of the Cu complex. Binding constants (K(b)) of DNA with the complex were calculated at different temperatures. Thermodynamic parameters, enthalpy and entropy changes were calculated according to Van't Hoff equation, which indicated that reaction is predominantly enthalpically driven. All these results indicate that Cu(II) complex interacts with CT-DNA via intercalative mode. Also, this new complex induced cleavage in pUC18 plasmid DNA as indicated in gel electrophoresis and showed excellent antitumor activity against K562 (human chronic myeloid leukemia) and human T lymphocyte carcinoma-Jurkat cell lines. PMID- 22093524 TI - Cerebral abscesses in hereditary haemorrhagic telangiectasia: a clinical and microbiological evaluation. AB - OBJECTIVES: Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder that can lead to neurological manifestations including strokes and cerebral abscesses. Our objectives were to describe clinical, radiological, bacteriological, and outcome characteristics of patients with cerebral abscess and HHT, and to concurrently compare this group with a control group with cerebral abscess, but without HHT. PATIENTS AND METHODS: Patients with HHT and cerebral abscess in 5 French medical centers were included. Their clinical, radiological, biological data and prognosis were compared to the data of unselected patients with cerebral abscesses but without HHT included during the same period of time. RESULTS: Twenty-six patients (13 men and 13 women; 44.7+/ 17.2; range 12-79 years), with HHT and cerebral abscess were included. A pulmonary arteriovenous malformation (AVM) was present in all cases. Cerebral abscesses were solitary, supratentorial, and mostly lobar. In all cases, pathogens were anaerobic or facultative anaerobic germs (particularly streptococcus). No death was observed, but various sequels were present in up to two-thirds of the patients. We observed a recurrence of the cerebral abscess in 4 patients with a mean delay of 81 months. In comparison with the control group, cerebral abscesses were generally of later recurrence and significantly more often unique and less often due to staphylococcus. CONCLUSION: HHT cerebral abscesses are particularly linked to pulmonary arteriovenous malformations and anaerobic germs. Their clinical, radiological and bacteriological characteristics are quite different than in a control group with more solitary brain localizations, no staphylococcus infection and a significantly longer interval to recurrence. PMID- 22093525 TI - A multilayered polyurethane foam technique for skin graft immobilization. AB - BACKGROUND: Several techniques are applicable for skin graft immobilization. Although the sponge dressing is a popular technique, pressure failure near the center of the graft is a weakness of the technique that can result in engraftment failure. OBJECTIVE: To evaluate the efficacy of a new skin graft immobilization technique using multilayered polyurethane foam in vivo and in vitro. METHODS AND MATERIALS: Twenty-six patients underwent a full-thickness skin graft. Multiple layers of a hydrocellular polyurethane foam dressing were used for skin graft immobilization. In addition, we created an in vitro skin graft model that allowed us to estimate immobilization pressure at the center and edges of skin grafts of various sizes. RESULTS: Overall mean graft survival was 88.9%. In the head and neck region (19 patients), mean graft survival was 93.6%. Based on the in vitro outcomes, this technique supplies effective pressure (<30 mmHg) to the center region of the skin graft. CONCLUSIONS: This multilayered polyurethane foam dressing is simple, safe, and effective for skin graft immobilization. PMID- 22093526 TI - Digoxin - time for its rehabilitation? PMID- 22093527 TI - DNA methylation profiling: a promising tool and a long road ahead for clinical applications. PMID- 22093528 TI - Power and control: contracts and the patient-physician relationship. PMID- 22093529 TI - Medicine and user involvement within European healthcare: a typology for European comparative research. PMID- 22093530 TI - Direct-to-consumer testing: more risks than opportunities. AB - As a result of incessant genetic discoveries and remarkable technological advancements, the availability and the consequent consumer's request for genetic testing are growing exponentially, leading to the development of a 'parallel' market, i.e. the direct-to-consumer (DTC) testing, also known as 'direct access testing' (DAT). Analogous to the traditional laboratory diagnostics, drawbacks of DTC testing might arise from any step characterising the total testing process, and include poor control of both appropriateness and preanalytical requirements, potential operation outside national or international regulation for in vitro diagnostic testing, little evidence of quality as well as the risk of transfer of genetic materials from the companies to other entities. Another important issue is the test panels offered to consumers, which are often based on preliminary, speculative or unsupported scientific information. Finally, the potential of this type of testing to generate anxiety or false reassurance should also be carefully considered. Although DTC testing carries some theoretical advantages (e.g. greater consumer autonomy and empowerment), solid clinical studies and costs vs. benefit analyses are needed to definitely establish whether DTC testing might be effective for decreasing the burden of diseases, delay their onset or modify their progression and therefore the clinical outcome. PMID- 22093531 TI - Mortality and morbidity of heart failure treated with digoxin. A propensity matched study. AB - BACKGROUND: The role of digoxin in the prognosis of patients with heart failure (HF) remains unclear. AIMS: To evaluate the relationship of commencing treatment with digoxin (CTDig) with the mortality and the morbidity of patients with HF. METHODS: Prospective study over 8 years on 4467 patients with HF. Main outcomes were all-cause and cardiovascular mortality, hospitalisations and visits. We analyse the independent relationship of CTDig, with the mortality and the morbidity, stratifying patients for cardiovascular comorbidity, after propensity score-matching for potential confounders (1421 patients who CTDig vs. another 1421 patients non-exposed to digoxin). RESULTS: During a median follow up of 46.1 months, 1872 patients (65.9%) died, and 2203 (77.5%) were hospitalised. CTDig was associated with a lower all-cause mortality (HR = 0.90 [95% CI, 0.84-0.97]), and cardiovascular mortality (HR = 0.87 [0.81-0.96]), hospitalisation (HR = 0.91 [0.86-0.97]), 30-day readmission for HF (HR = 0.88 [0.79-0.95]), and visits (HR = 0.94 [0.90-0.98]) (p < 0.001 in all cases), after adjustment for the propensity to take digoxin, other medications, and other potential confounders. These effects of digoxin were independent of gender, or type of HF (systolic or non systolic). CONCLUSION: The data suggest that therapy with digoxin is associated with an improved mortality and morbidity of HF, including women and patients with non-systolic HF. PMID- 22093532 TI - Differences between South Asians and White Europeans in five year outcome following percutaneous coronary intervention. AB - AIMS: The aim of this study was to compare rates of target lesion revascularisation (TLR) and total mortality between South Asians (SAs) and White Europeans (WEs) following percutaneous coronary intervention (PCI). METHODS: We followed a cohort of 293 SAs and 865 WEs patients admitted for elective or urgent PCI to de novo lesions. For each patient, baseline cardiovascular risk factors and angiographic data were obtained. Patients had long-term follow-up for all cause mortality and TLR. RESULTS: Patients were followed up over a median period of 54 months (inter-quartile range: 47-65). SAs were younger (62 +/- 12 years vs. 66 +/- 11 years; p < 0.0001), with a higher prevalence of diabetes, greater social deprivation [Carstairs score: 10.2 (IQR 6.5-12.1) vs. 3.3 (IQR 0.9-6.5); p < 0.0001] and presented more acutely (urgent PCI procedure). During the follow-up period, a total of 119 deaths and 111 TLR [94 repeat PCI and 17 coronary artery bypass grafting (CABG)] occurred. There was no significant difference in the rate of long-term all-cause mortality between SA and WE [31 (10.6%) vs. 107 (12.4%); OR: 0.84 (0.55-1.28); p = 0.47]. However, SA ethnicity was an independent predictor of long-term TLR, after adjusting for baseline clinical and procedural characteristics [54 (18.4%) vs. 57 (6.6%); OR: 2.83 (1.87-4.29); p < 0.0001]. CONCLUSIONS: South Asian patients were more likely to require re-admission to treat clinical restenosis of the index lesion. There was no significant long-term difference in all-cause mortality between SA and WE patients. PMID- 22093533 TI - Coronary computed tomography angiography for the evaluation of patients with acute chest pain. AB - Acute chest pain is a common presenting complaint of patients attending emergency room departments. Despite this, it can often be challenging to completely exclude a diagnosis of acute coronary syndrome following an initial standard clinical and biochemical evaluation. As a result of this, patients are often admitted to hospital until the treating clinician is satisfied that this diagnosis can be excluded. This process imparts a significant health economic burden by not only increasing hospital bed occupancy rates but also by the unnecessary layering of diagnostic investigations. With the rapid advances in coronary computed tomography angiography (CTA), there has been considerable interest in whether coronary CTA may be a viable alternative to this current standard care. We review the current literature and supporting evidence for utilising coronary CTA in the evaluation of patients presenting with acute chest pain in terms of its diagnostic accuracy, safety, cost-effectiveness and prognostic implications. PMID- 22093534 TI - Systolic heart failure in South Asians. AB - Heart failure (HF) is a common condition leading to an unfavourable prognosis and impaired quality of life. In this review, we provide an overview of published literature on possible epidemiological and pathophysiological differences between patients with systolic HF of South Asian origin and those from other ethnic groups (mainly White). Systolic HF tends to manifest earlier among South Asians and with frequent hospital admissions. However, survival for such patients appears to be significantly better compared with the White group, which might be associated with different patterns of HF. For example, this could be attributed to a lower prevalence of left ventricular systolic dysfunction in South Asian subjects. Indeed, the high prevalence of hypertension and diabetes among South Asians may predispose to diastolic HF with preserved systolic function. In addition, because of underrepresentation of South Asians in clinical trials, there are little data on optimal management of this ethnic group. PMID- 22093535 TI - 'Catching the spike and tracking the flow': Holter-temperature monitoring in patients admitted in a general internal medicine ward. AB - OBJECTIVE: To study if a 24-h continuous monitoring of temperature reveals information not accessible through conventional care. This included omitted fever peaks and circadian and complexity characteristics that may correlate with specific aetiologies. DESIGN: Ours was a prospective, observational study. A total of 62 patients, admitted to a general internal medicine ward, in whom a temperature > 38 degrees C had been observed the day before inclusion underwent a 24-h long continuous monitoring of both central and peripheral temperatures. The time series were recorded in a file, while they otherwise followed conventional care. Time series were analysed for standard statistics, chronobiological analysis (amplitude, mesor, acrophase, intra-daily variability) and complexity analysis (Approximate Entropy of both central and peripheral temperature, cross-ApEn). A month after discharge, the clinical reports were reviewed and a definitive diagnosis of the febrile syndrome was established. RESULTS: A total of 62 patients were initially included. In six cases, no time series could be obtained because of technical problems, leaving 56 patients accessible for analysis. In 10 cases, no definitive diagnosis was established. Continuous monitoring detected a mean of 0.7 (CI = 0.27-1.33) peaks of fever (central temperature > 38.0 degrees C) unobserved by conventional care per patient. A proportion of 16% (CI = 6-26) of patients considered afebrile by conventional care had at least one fever peak detected by continuous monitoring. Circadian rhythm persisted or was exacerbated in febrile patients. Circadian amplitude was increased in patients with tuberculosis. Complexity analysis did not differ among different diagnostic groups, although in subgroup analysis, viral infections had a higher complexity than other infectious diseases. CONCLUSIONS: Temperature Holter monitoring reveals fever peaks that pass otherwise unobserved. Furthermore, chronobiological and complexity analysis of the temperature profile may provide quick and easy 'hidden information', not available to conventional care. PMID- 22093536 TI - Pharmacological treatment and the prospect of pharmacogenetics in Parkinson's disease. AB - Parkinson disease (PD) is a progressive movement disorder marked by tremor, rigidity, bradykinesia and postural instability. Levodopa (l-dopa), usually combined with a peripheral dopa decarboxylase inhibitor, has been proved to provide the best symptomatic benefit for PD. However, its long-term efficacy is limited because of motor complications and drug-induced dyskinesia. Dopamine agonists, catechol-O-methyltransferase inhibitors and monoamine oxidase-B inhibitors are anti-parkinsonian (anti-PD) drugs that have been found to further improve the potency of l-dopa and prevent the onset of motor complications. However, as PD is a progressive disorder, all the drugs used for its therapy, manifest reduced efficacy and adverse effects with time. Research on the field of pharmacogenetics has pointed out that the genetic variability of each individual determines to a large extent the inter-individual variability in response to anti PD drugs. Clinicogenetic trials show that drug efficacy or toxicity or susceptibility to side effects are features governed by genetic principles. This article is a review of the present pharmacological treatment of PD and current pharmacogenetic data for PD. PMID- 22093537 TI - The association of antihypertensive medication use with risk of cognitive decline and dementia: a meta-analysis of longitudinal studies. AB - The association of antihypertensive medication use with cognitive decline (including mild cognitive impairment) or dementia (including Alzheimer's disease (AD), vascular dementia (VD) and any dementia) has still been an area of controversy. This study examined the association of antihypertensive medication use with cognitive decline or dementia using a quantitative meta-analysis of longitudinal studies. EMBASE and MEDLINE were searched for articles published up to Feb 2011. All studies that examined the relationship between antihypertensive medication use and the incidence of dementia or cognitive decline were included. Pooled relative risk (RR) was calculated using fixed and random-effects models. Fourteen studies met our inclusion criteria for this meta-analysis. All subjects were without dementia or cognitive impairment at baseline. There were subjects with (32,658) and without (36,905) antihypertensive medication use. The quantitative meta-analysis showed that there was no significant difference in incidence of AD (RR: 0.90, 95% confidence interval (CI): 0.79-1.03), cognitive decline (RR: 0.97; 95% CI: 0.92-1.03) and cognitive impairment (RR: 0.97; 95% CI: 0.92-1.03). The quantitative meta-analysis showed that the subjects with antihypertensive medication use were lower incidence of VD (RR: 0.67, 95% CI: 0.52-0.87) and any dementia (RR: 0.87; 95% CI: 0.77-0.96) than those without. The quantitative meta-analysis showed that antihypertensive medication use could decrease risk of the development of VD and any dementia, but could not decrease that of AD, cognitive decline and cognitive impairment. PMID- 22093538 TI - Rheumatic-musculoskeletal pain and disorders in a naive group of individuals 15 months following a Chikungunya viral epidemic in south India: a population based observational study. AB - BACKGROUND: Prospective community data on arthropathy following Chikungunya (CHIKV), a self-limiting, arboviral infection, causing debilitating arthropathy are lacking. The clinical profile of chronic rheumatic-musculoskeletal (RMSK) pain and disorders, captured inadvertently about 15 months following a CHIKV epidemic is described. MATERIALS AND METHODS: Patients with RMSK pain following the CHIKV epidemic in 2007 were identified from a randomly selected population of 5277 (Age > 15 years) in a village in south India, using a validated questionnaire-based house-to-house survey. Typical narration, records and serology were relied upon to classify CHIKV. Respondents who recorded active pain sites on a human mannequin were evaluated by Rheumatology physicians. RESULTS: A total of 1396 CHIKV infected individuals with painful MSKD were identified, of whom 437 patients (mean age: 48.37 +/- 13.62 years; 71.6% women) who were naive to RMSK pain prior to the epidemic were studied in detail. Incidence of RMSK pain and disorders in the naive group was 8.3% (437/5277). Knee was the commonest self reported pain site (83.3%). Majority of the patients (57%) had postviral non specific polyarthralgia. Soft tissue rheumatism was very common (27.7%). Rheumatoid arthritis and seronegative spondyloarthritis were observed in 6 and 11 patients, respectively. CONCLUSIONS: Although a causal association could not be established, this study has unravelled a wide spectrum of unrecognised post-CHIKV chronic RMSK disorders. Aetiopathogenesis and risk factors of chronicity need to be studied further. PMID- 22093539 TI - Aberrant methylation of genes in stool samples as diagnostic biomarkers for colorectal cancer or adenomas: a meta-analysis. AB - BACKGROUND: An increasing number of hypermethylated genes in stool samples have been reported as biomarkers for the detection of colorectal cancer (CRC) or adenomas. We aimed to comprehensively review and compare the evidence for feasibility of using these biomarkers for the detection of colorectal neoplasia. METHODS: We searched Medline, the Web of Science and OVID for studies that used hypermethylated genes as biomarkers for the detection of CRC or adenomas. A meta analysis was carried out using the random-effect model with diagnostic odd ratios (DOR) and 95% confidence intervals (CI) as effect measurements. RESULTS: A total of 19 studies including 2,356 patients were eligible for final analysis. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and DOR for the detection of CRC or adenomas were 0.62 (95% CI: 0.51-0.71), 0.89 (95% CI: 0.86-0.92), 5.66 (95% CI: 4.68-6.83), 0.43 (95% CI: 0.34-0.55) and 13.15 (95% CI: 9.82-17.60) respectively. Of these, the sensitivity and specificity for the detection of adenoma were 0.54 (95% CI: 0.39-0.68) and 0.88 (95% CI: 0.83 0.92) respectively. CONCLUSIONS: Hypermethylated gene panels are not currently accurate enough to be used alone for colorectal neoplasia screening. The discovery and evaluation of additional biomarkers with improved sensitivity and specificity is necessary. PMID- 22093540 TI - Non-adherence to lipid-lowering therapies: a need for more studies to evaluate reasons for medication non-adherence. PMID- 22093541 TI - Adherence to lipid-lowering agents. PMID- 22093542 TI - [Systemic follicular lymphoma with cutaneous manifestations and exclusively cutaneous recurrence]. PMID- 22093543 TI - [Methotrexate in psoriasis: do we need to give a test dose?]. PMID- 22093545 TI - Angiotensin-degrading serine peptidase: a new chymotrypsin-like activity in the venom of Bothrops jararaca partially blocked by the commercial antivenom. AB - Snakebite envenomation is considered a highly relevant public health hazard in South America, having an impact in terms of mortality and morbidity. In Brazil, Bothrops (sensu latu) poisoning is responsible for 90% of the snakebites and in patients treated at the Vital Brazil Hospital (Butantan Institute) this index reaches 97.5%. The objective of the present study was to analyze more specifically the ability of the antibothropic antivenom, produced by the Butantan Institute, Sao Paulo, Brazil, to neutralize metallo-and serine peptidases, known as the major toxins present in Bothrops jararaca venom. A set of Fret peptides (Free Ressonance Energy Transfer) was studied using the BjV (B. jararaca venom) and site-directed inhibitors PMSF, EDTA and 1,10-phenanthroline. Two substrates were reached to be used as specific tools for studies with metallo peptidases, Abz-FASSAQ-EDDnp, and the serine peptidases, Abz-RPPGFSPFRQ-EDDnp. In disagreement with the literature, the use of both substrates and the antibothropic serum showed a weak neutralization of the serine peptidases present in this venom and a strong neutralization of the metallo peptidases. In order to investigate possible mechanisms of action that have not yet been described for the serine peptidases from the BjV, the present study shows for the first time a new tyrosine-specific chymotrypsin-like and angiotensin-degrading serine peptidase activity, that was partially blocked by the antibothropic serum. In conclusion, the antivenom presented a good neutralization of metallo peptidases but not of serine peptidases, indicating that further studies about serine peptidases immunogenicity are necessary to improve the antibothropic serum. PMID- 22093544 TI - A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes. AB - BACKGROUND: The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. METHODS: We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. RESULTS: Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34) compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two <=10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806). One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively). No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. CONCLUSIONS: Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are needed to determine the role of hypocaloric sweeteners in a wider population health strategy to prevent, reduce and manage obesity and its consequences. PMID- 22093546 TI - Presumed cytomegalovirus-associated retrobulbar optic neuritis in a patient after allogeneic stem cell transplantation. AB - A case of cytomegalovirus (CMV)-associated bilateral retrobulbar optic neuritis (ON) following haploidentical hematopoietic stem cell transplantation (haplo HSCT) is reported. Abrupt onset of bilateral decreased vision occurred in a 33 year-old man 7 months after haplo-HSCT. His cerebrospinal fluid (CSF) demonstrated pleocytosis with an absence of leukemic cells. CMV DNA was detected in his blood and CSF sample. Neither encephalopathy nor retinopathy was found in this patient. He was diagnosed with bilateral retrobulbar ON. Although he was given enough antiviral treatment against CMV and immunosuppression with high-dose methylprednisolone, the patient's vision showed no improvement, and he has almost total bilateral blindness. This is the first report, to our knowledge, of CMV associated bilateral retrobulbar ON in allogeneic stem cell transplantation. PMID- 22093548 TI - Dietary n-3 PUFA affect lipid metabolism and tissue function-related genes in bovine muscle. AB - Gene expression profiles of bovine longissimus muscle as affected by dietary n-3 v. n-6 fatty acid (FA) intervention were analysed by microarray pre-screening of >3000 muscle biology/meat quality-related genes as well as subsequent quantitative RT-PCR gene expression validation of genes encoding lipogenesis related transcription factors (CCAAT/enhancer-binding protein beta, sterol regulatory element-binding transcription factor 1), key-lipogenic enzymes (acetyl CoA carboxylase alpha (ACACA), fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD)), lipid storage-associated proteins (adipose differentiation related protein (ADFP)) and muscle biology-related proteins (cholinergic receptor, nicotinic, alpha1, farnesyl diphosphate farnesyl transferase 1, sema domain 3C (SEMA3C)). Down-regulation of ACACA (P = 0.00), FASN (P = 0.09) and SCD (P = 0.02) gene expression upon an n-3 FA intervention directly corresponded to reduced SFA, MUFA and total FA concentrations in longissimus muscle, whereas changes in ADFP (P = 0.00) and SEMA3C (P = 0.05) gene expression indicated improved muscle function via enhanced energy metabolism, vasculogenesis, innervation and mediator synthesis. The present study highlights the significance of dietary n-3 FA intervention on muscle development, maintenance and function, which are relevant for meat quality tailoring of bovine tissues and modulating animal production-relevant physiological processes. PMID- 22093549 TI - Gestational age dependent content, composition and intrauterine accretion rates of fatty acids in fetal white adipose tissue. AB - BACKGROUND: Little is known about the gestational age (GA) dependent content, composition and intrauterine accretion rates of fatty acids (FA) in fetal white adipose tissue (WAT). OBJECTIVE & DESIGN: To acquire this information, we collected abdominal subcutaneous WAT samples from 40 preterm and term fetuses. Their GA ranged from 22 to 43 weeks. FA were expressed as mg/g wet WAT and g/100g FA (g%). Intrauterine WAT FA accretion rates were estimated for appropriate (AGA) and large (LGA) for gestational age infants. RESULTS: From 25 to 40 weeks gestation, saturated-FA (SAFA) increased from 83 to 298 mg/g WAT and monounsaturated-FA (MUFA) from 83 to 226 mg/g WAT, while polyunsaturated-FA (PUFA) increased insignificantly from 18.0 to 23.2 mg/g WAT. As percentages of total FA, SAFA increased from 46 to 55 g%, MUFA decreased from 44 to 41 g%, and PUFA from 10.3 to 4.26 g%. Docosahexaenoic (DHA) and arachidonic acid (AA) accretion rates in WAT during the 3rd trimester for AGA infants were 88 and 193 mg/week, respectively. Contemporaneous DHA and AA accretion rates for 4500 g LGA infants were 184 and 402 mg/week, respectively. Compared to the whole 3rd trimester, increment rates during the last 5 weeks of gestation were about 2-fold higher. CONCLUSION: FA accretion rates, notably those of DHA and AA, may be important for designing nutritional regiments for preterm infants. The current WAT-DHA and WAT-AA accretion rates are considerably lower than previously reported in the literature. PMID- 22093550 TI - [Furthering the standardized clinical study on gastroesophageal reflux disease]. PMID- 22093547 TI - Inhibition of cathepsin B activity attenuates extracellular matrix degradation and inflammatory breast cancer invasion. AB - INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC. METHODS: We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real time the degradation of type IV collagen by IBC cells. IBC patient biopsies were examined for expression of cathepsin B and caveolin-1. RESULTS: Both cell lines expressed comparable levels of cathepsin B and uPA. In contrast, levels of caveolin-1 and uPAR were greater in SUM149 cells. We observed that uPA, uPAR and enzymatically active cathepsin B were colocalized in caveolae fractions isolated from SUM149 cells. Using a live-cell proteolysis assay, we demonstrated that both IBC cell lines degrade type IV collagen. The SUM149 cells exhibit predominantly pericellular proteolysis, consistent with localization of proteolytic pathway constitutents to caveolar membrane microdomains. A functional role for cathepsin B was confirmed by the ability of CA074, a cell impermeable and highly selective cathepsin B inhibitor, to significantly reduce pericellular proteolysis and invasion by SUM149 cells. A statistically significant co expression of cathepsin B and caveolin-1 was found in IBC patient biopsies, thus validating our in vitro data. CONCLUSION: Our study is the first to show that the proteolytic activity of cathepsin B and its co-expression with caveolin-1 contributes to the aggressiveness of IBC. PMID- 22093551 TI - [Design is determinative for success: experience and lessons from large international clinical trials]. PMID- 22093552 TI - [Interpretation of new guidelines for adult cardiopulmonary resuscitation]. PMID- 22093553 TI - [A retrospective analysis of clinical characteristics and mortality of gastrointestinal bleeding in 414 elderly patients]. AB - OBJECTIVE: To analyze clinical characteristics of patients with gastrointestinal bleeding (GIB) and the death-related risk factors. METHODS: A retrospective analysis was conducted in 414 patients hospitalized for GIB during a 16-year period of 1994 to 2009. Logistic regression analysis identified predictors of mortality. RESULTS: The mean age of the 414 patients is 83.5 years old, ranging from 65 to 96 years old. The main causes of GIB were peptic ulcer (33.1%, 137/414), gastroduodenal mucosal erosion (28.5%, 118/414) and tumor (21.0%, 87/414). The main symptom was melena (71.0%, 294/414). Drugs that induced GIB were mainly non-steroidal anti-inflammatory drugs, including aspirin (11.1%, 46/414), acetaminophen (8.9%, 37/414) and indomethacin (1.9%, 8/414). 14% of patients (58/414) died of GIB in 30 days. The proportion of drug-induced GIB and gastroduodenal mucosal erosion caused GIB had increased significantly during the period of 2004 to 2009 (P < 0.05). Analysis of 30-day mortality risk showed advanced age, low diastolic blood pressure, high heart rate, low hemoglobin levels at presentation and hemorrhage volume in dead GIB elderly patients were significantly different compared with GIB elderly patients alive. Presence of severe comorbidity (heart failure and renal failure) and caused by cirrhosis and portal hypertension in GIB elderly patients were the only independent predictors of 30-day mortality (P < 0.001). CONCLUSIONS: Death of GIB patients occurred predominantly in elderly patients with severe comorbidities and systemic conditions at presentation. PMID- 22093554 TI - [The endoscopic and clinical features of Indigo Naturalis-associated ischemic lesions of colonic mucosa]. AB - OBJECTIVE: By analysing the clinical features of Indigo Naturalis-associated ischemic lesion of colon mucosa to improve the precautionary and therapeutic level of the disease. METHODS: Thirteen patients diagnosed as Indigo Naturalis associated ischemic lesion of colon mucosa in Peking University Third Hospital from 2005 to 2010 were reviewed. The endoscopic and clinical features were analysed. RESULTS: The 13 patients with an average age of (60.6 +/- 14.1) years old were prescribed Chinese traditional medicine containing Indigo Naturalis for psoriasis or idiopathic thrombocytopenic purpura (ITP). The ratio of males to females was 1:1.6. The typical manifestations were abdominal pain and bloody stool with watering diarrhea before bloody stool in 61.5% patients. Endoscopic and pathological characteristics were coincident with ischemic lesion and more like a chronic index. Vasodilatic medicine was effective and the average hemostatic time was (1.7 +/- 0.8) days. The prognosis was well and no recurrence was found during 3 months follow-up. CONCLUSIONS: Patients having psoriasis or ITP treated with Chinese traditional medicine containing Indigo Naturalis have an inclination to colon mucosa lesions, even ischemic lesion. Careful assessment and observation before prescribing are necessary in these patients. PMID- 22093555 TI - [An analysis of clinical characteristics of forty-six AIDS phobia patients]. AB - OBJECTIVE: To summarize the clinical characteristics of AIDS phobia patients and establish the preliminary clinical diagnostic criteria. METHODS: The clinical information of 46 AIDS phobia patients was collected and summarized. General demographic data, clinical manifestations and laboratory results were analyzed. RESULTS: The clinical characteristics of AIDS phobia patients include: (1) With or without high-risk behavior of HIV-1 infection; (2) Patients repeatedly demanded HIV/AIDS related laboratory tests, suspected or believed in HIV-1 infection with daily life affected; (3) The main complaints were non-specific including influenza-like symptoms (headache, sore throat and so on), fasciculation, formication, arthrodynia, fatigue and complaint of fever with normal body temperature; physical examination did not reveal any positive physical sign except white coated tongue; (4) Symptoms mainly appeared 0-3 months after the high-risk behavior while HIV-1 antibody kept negative; (5) T lymphocyte subsets test was carried out in 23 patients and showed 19 (82.6%) with CD(4)(+) T lymphocyte count > 500/ul, the remaining 4 were 300 - 500/ul, with the lowest count of 307/ul. Few patients had inversed CD(4)(+)/CD(8)(+) ratio but without excessive CD(8)(+)T lymphocyte activation. CONCLUSIONS: AIDS phobia is a complicated physical and mental disease, whose diagnosis and treatment still need further investigation. PMID- 22093556 TI - [Blood stream infections during agranulocytosis period after hematopoietic stem cell transplantation in one single center]. AB - OBJECTIVE: To analyze the epidemiologic features of blood stream infection (BSI) during the period of agranulocytosis after hematopoietic stem cell transplantation (HSCT) in our hospital, and provide the basis for the empirical therapy. METHODS: The consecutive hematopoietic stem cell transplantation recipients conducted between January 2008 and October 2010 were studied retrospectively, to identify the current incidence, etiology for BSI and associated mortality during the period of agranulocytosis. RESULTS: Totally 75 patients were diagnosed as BSI. The incidence of BSI was 9.6% (75/784) in HSCT during the period of agranulocytosis, 17.0% (75/441) in febrile patients. The pathogen testing showed that 64.4% were G(-) bacteria, 30.1% were G(+) bacterial and 5.5% were fungi. All G(-) bacteria except one were sensitive to carbapenems; all G(+) bacteria except one were sensitive to vancomycin. Among the 75 patients, 9 (12.0%) experienced septic shock and 5 (6.7%) died. CONCLUSIONS: The pathogens of the BSI in the cohort are G(-) bacteria, followed by G(+) bacteria and fungi. Carbapenems and vancomycin are the first drugs for the experiential therapy. PMID- 22093557 TI - [The relationship between hyperuricaemia and clinic pathology of IgA nephropathy]. AB - OBJECTIVE: To analyze the correlation between the level of serum uric acid and the clinical and pathological features of IgA nephropathy. METHODS: Totally 148 patients diagnosed as IgA nephropathy by renal biopsy in our hospital from January 2007 to December 2010 were divided into hyperuricaemic group (41 cases) and non-hyperuricaemic group (107 cases) according to the level of serum uric acid. The clinical parameters and renal pathology grade were compared. RESULTS: There were significant differences between hyperuricaemic group and non hyperuricaemic group in the incidences of hypertension (63.4% vs 38.3%), disease duration [(18.90 +/- 10.12) months vs (9.46 +/- 3.91) months] and body mass index [(22.81 +/- 3.60) kg/m(2) vs (15.32 +/- 2.54) kg/m(2)] (all P < 0.05), while no differences in age and sex (both P > 0.05). The blood urea nitrogen (BUN) [(8.93 +/- 4.28) mmol/L vs (5.21 +/- 2.18) mmol/L], creatinine (Cr) [(155.96 +/- 107.72) umol/L vs (79.52 +/- 40.01) umol/L], serum triglycerides [(2.11 +/- 1.06) mmol/L vs (1.86 +/- 1.20) mmol/L] and 24-hour urine protein amount [(4328.16 +/- 1434.25) mg/24 h vs (2885.10 +/- 1388.15) mg/24 h] were significantly different between the two groups (all P < 0.05). The percentage of Lee's grade I + II in hyperuricaemic group was 12.2%, and IV + V grade was 39.0%, while percentage of Lee's grade I + II in non-hyperuricaemic group was 25.2%, and IV + V grade was 16.9% (P < 0.05). Tubulointerstitial lesions (TIL) grade III + IV was more in hyperuricaemic group, which was 68.3%, while TIL grade II was more in non hyperuricaemic group, which was 76.6%. Renal artery damage grade II + III was more in hyperuricaemic group, which was 73.2%, while renal artery damage grade 0 + I was more in non-hyperuricaemic group, which was 69.2%. CONCLUSIONS: The level of serum uric acid was related with 24-hour urine protein amount, blood pressure and kidney function in IgA nephropathy, and Lee's grade, TIL grade and renal artery damage grade were severe in hyperuricaemic group. PMID- 22093559 TI - [The significance of cough reflex sensitivity test in chronic cough]. AB - OBJECTIVE: Preliminary study of the cough reflex sensitivity test in chronic cough patients with different gender, disease duration and causes to evaluate the clinical diagnostic significance of the test and further provide some information for the treatment of chronic cough. METHODS: Totally 108 chronic cough patients in our hospital were enrolled in the study with the final diagnosis of upper airway cough syndrome (UACS), cough variant asthma (CVA) and gastroesophageal reflux cough (GERC). They all went through the cough reflex sensitivity test and the retrospective analysis of the results was made. RESULTS: In 108 patients with chronic cough (76 UACS, 19 CVA and 13 GERC), lgC5 was significantly slower in the female (1.80) than the male (2.40, P < 0.05) and in the patients with cough duration over 12 months (1.80) than those with cough duration under 12 months (2.40, P < 0.05). Cough sensitivity in patients with different causes was significantly different (P < 0.05) with lower lgC5 in GERC patients (1.49) than CVA (2.40, P < 0.05) and UACS (2.40, P < 0.05) patients. CONCLUSIONS: Cough sensitivity is different in chronic cough patients with different gender, disease duration and causes. Cough reflex sensitivity test is of great value in the etiology diagnosis of chronic cough. PMID- 22093558 TI - [The relationship between coagulation/anticoagulation imbalance and oxidative stress in patients with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To explore the relationship between coagulation/anticoagulation imbalance and oxidative stress in the patients with chronic obstructive pulmonary disease during acute exacerbation (AECOPD) before and after treatment. METHODS: Plasma tissue factor (TF) and tissue factor pathway inhibitor (TFPI) activity was detected by chromogenic assay in 28 AECOPD patients before and after treatment as well as in 30 healthy controls. The total antioxidative capacity (TAC), malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) in plasma were measured in both groups. RESULTS: The levels of plasma TF and TFPI, and their ratio (TF/TFPI) in AECOPD patients before treatment were significantly higher than those after treatment (all P < 0.01), the latter were still higher than those in the healthy persons (all P < 0.01). The levels of the TAC and GSH-PX in plasma in AECOPD patients before treatment were significantly lower than those after treatment (all P < 0.01), the latter were still lower than those in the healthy persons (all P < 0.01). The plasma MDA in AECOPD patients before treatment was significantly higher than that after treatment (P < 0.01), which was still higher than that in the healthy persons (P < 0.05). There were negative correlations between TF/TFPI ratio and TAC (r = -0.518, P < 0.01), GSH-PX (r = -0.454, P < 0.05), PaO2 (r = -0.511, P < 0.01) respectively and a positive correlation between TF/TFPI ratio and the percentage of neutrophils (r = 0.379, P < 0.05) in AECOPD patients before treatment. There still were negative correlations between TF/TFPI ratio and TAC (r = -0.420, P < 0.05), FEV(1)% to predicted (r = -0.480, P < 0.05) respectively, and a positive correlation between TF/TFPI ratio and MDA (r = 0.451, P < 0.05) in AECOPD patients after treatment. CONCLUSIONS: There existed coagulation/anticoagulation imbalance and oxidation/antioxidation imbalance before and after treatment in AECOPD patients and their relationship was explored. PMID- 22093560 TI - [An analysis of factors for quality-of-life in patients with chronic cough]. AB - OBJECTIVE: To constitute a correlation with the subjective indicators by investigation of the causes and clinical features in patients with chronic cough. METHODS: Totally 100 patients with chronic cough were recruited followed a diagnostic program. Airway responsiveness [by methacholine challenge test (MCT)], Leicester cough questionnaire (LCQ), visual analogue scale (VAS), cough score, age, gender and disease duration were all recorded for analysis. RESULTS: The top five causes of chronic cough in these patients were variant asthma, post infectious cough, atopic cough, eosinophilic bronchitis and upper airway cough syndrome. LCQ total score was negatively correlated with age and the VAS score (r = -0.239 and -0.470 respectively, all P < 0.05), while no difference was found among patients with different causes of disease or gender (F = 1.233, t = 1.918, all P > 0.05) and no correlation was found with BMI (r = -0.029, P > 0.05). The physiological and psychological field score in female patients significantly reduced (t = 2.174, 1.990, P < 0.05), and LCQ total score of MCT positive patients obviously reduced than negative ones (t = -2.22, P < 0.05). After the treatment of two weeks, LCQ three component field and total score could be improved significantly (all P < 0.01). CONCLUSIONS: Gender and age may have some impact on the quality of life in patients with chronic cough. LCQ, VAS and cough score should be used to assess cough severity and evaluate therapeutic effect in patients with chronic cough. PMID- 22093561 TI - [The relationship between left ventricular diastolic function and arterial stiffness in diabetic coronary heart disease]. AB - OBJECTIVES: By measuring left ventricular diastolic function and arterial stiffness, this study aims to probe into the effect of diabetes mellitus (DM) on left ventricular diastolic function and arterial stiffness, and evaluate the correlation between left ventricular diastolic function and arterial stiffness. METHODS: Seventy-six inpatients were enrolled. According to their coronary angiography, OGTT test results and past history of DM, patients were divided into controlled, CHD (coronary heart disease with no DM), and CHD + DM groups. Through invasive hemodynamic monitoring during left ventricular angiography, left ventricular end-diastolic pressure (LVEDP) and tau index were collected. Carotid femoral pulse wave velocity (c-f PWV), reflected wave augmentation index (AIx@75) and other data reflecting the degree of arterial stiffness were collected bedside with non-invasive means. SPSS 18.0 was used for statistical analysis. RESULTS: No significant difference was found between groups for LVEDP, tau index, and AIx@75. In terms of c-f PMV, The CHD + DM group (8.79 +/- 1.59) cm/s differed significantly from the CHD group (7.43 +/- 1.42) cm/s and the controlled group (6.83 +/- 1.14) cm/s. No correlations were found between c-f PMV and LVEDP or tau index. A positive correlation was found between AIx@75 and tau index. CONCLUSIONS: Compared with the controlled group and CHD patients with no DM, CHD + DM patients show worse arterial stiffness with no difference in ventricular diastolic function. There is a positive correlation between arterial stiffness and diastolic dysfunction. PMID- 22093562 TI - [The relationship between amount of cigarette smoked and insulin resistance in male patients with coronary artery disease]. AB - OBJECTIVE: To investigate the relationship between smoking and insulin resistance in non-obese male patients with CAD. METHODS: 414 consecutive non-obese male patients with angiographically-documented CAD (luminal diameter narrowing > 50%) were recruited, including 113 nonsmokers and 301 smokers. With 99 mild smokers (< 400 packs/year), 95 medium smokers (400 - 799 packs/year) and 107 heavy smokers (>= 800 packs/year). Insulin resistance index (IRI) was expressed by homeostasis model assessment for insulin resistance (HOMA-IR) calculated by the formula of [fasting serum glucose (mmol/L) * fasting plasma insulin (mU/L)]/22.5. IRI >= 2.69 was defined as insulin resistance, while IRI < 2.69 was insulin sensitive. Fasting glucose, fasting insulin and IRI were recorded and odds ratio for the incidence of insulin resistance was calculated. RESULTS: Fasting glucose was higher in heavy smokers (5.86 mmol/L) than that in nonsmokers (5.51 mmol/L, P = 0.037) and mild smokers (5.33 mmol/L, P = 0.014). Fasting insulin and IRI were also significantly higher in heavy smokers (10.25 mU/L) than those in non-smokers (8.72 mU/L, P = 0.0231, respectively) and mild smokers (8.67 mU/L, P = 0.0231). Compared with nonsmokers, the odds ratio for the incidence of insulin resistance was 1.53 (95%CI 0.55 - 2.94; P = 0.027) in medium smokers and 1.89 (95%CI 0.49 - 3.14; P = 0.018) in heavy smokers. CONCLUSIONS: The relationship between smoking and insulin resistance is highly dose dependent in non-obese male patients with CAD. PMID- 22093563 TI - [The cytogenetic characteristics of 178 acute myeloid leukemia patients]. AB - OBJECTIVE: To explore the cytogenetic characteristics of acute myeloid leukemia (AML) patients. METHODS: The karyotype analysis was performed in 178 AML using the short-term culture of bone marrow cell and G-banding technique. RESULTS: Among the 178 patients, 171 had enough metaphases for analysis and 128 (74.9%) had clonal karyotypic abnormalities. Twenty-seven patients were secondary to myelodysplastic syndrome (MDS-AML), with 25 (92.6%) patients carrying clonal karyotypic abnormalities. Among the remaining 144 patients of de novo AML, 103 (71.5%) had clonal karyotypic abnormalities. The rate of abnormal clonal karyotype was higher in MDS-AML than that of de novo AML (P = 0.021). Among the 171 patients, 41 (24.0%) were in favorable risk group, 80(46.8%) in intermediate risk group and 50 (29.2%) in adverse risk group. t(15;17) was the most common chromosomal aberration. The majority intermediate risk chromosomal aberration was normal karyotype. The most common cytogenetic abnormality among adverse group was a complex karyotype. Adverse cytogenetic aberrations, such as -5/5q-, -7/7q-, frequently occurred in conjunction with one another as part of a complex karyotype. Totally 75 patients were 60 years or older, among them, 16.0% were in favorable risk group, 48.0% in intermediate risk group and 36.0% in adverse risk group. Among 96 younger patients, 30.2% were in favorable risk group, 45.8% in intermediate risk group and 24.0% in adverse risk group. The rate of favorable risk chromosomal aberration was lower in elder patients than in younger (P = 0.031). The rate of adverse risk chromosomal aberration and the rate of monosomal karyotype were higher in MDS-AML than in de novo AML patients (P < 0.001). CONCLUSIONS: The most common favorable, intermediate and adverse chromosomal aberrations were t(15;17), normal karyotype and complex karyotype respectively. The karyotype was poor in MDS-AML and elder AML patients. PMID- 22093564 TI - [The clinical analysis of mercury poisoning in 92 cases]. AB - OBJECTIVE: To summarize the clinical features of mercury poisoning diagnosed by blood and urine tests for improving the diagnosis and treatment of the disease. METHODS: Poisoning causes, clinical manifestations, diagnosis, treatment and prognosis were retrospectively reviewed in 92 in-patients with mercury poisoning in our hospital from January 2000 to April 2010. RESULTS: Of the 92 patients, 37 were male and 55 were female with an average age of 33.1 (2 - 65) years old. The mercury poisoning was caused by occupational exposure and non-occupational exposure, such as iatrogenic exposure, life exposure and wrong intake or suicidal intake of mercury-containing substances, mainly through respiratory tract, digestive tract and skin absorption. The most common clinical symptoms were as the followings: nervous system symptom, such as memory loss in 50 cases (54.3%), fatigue in 34 (37.0%), numb limb in 25 (27.2%), dizziness and headache in 22 (23.9%), cacesthesia in 20 (21.7%), fine tremor (finger tip, tongue tip, eyelids) in 15 (16.3%), insomnia and more dreams in 12 (13.0%); gastrointestinal symptoms: nausea in 16 (17.4%), abdominal pain in 14 (15.2%), stomatitis in 5 (5.4%); joint and muscle symptoms: muscle pain in 16 (17.4%), joint pain in 5 (5.4%); cardiovascular system: chest tightness, heart palpitations in 6 (6.5%); urinary system: edema in 9 (9.8%); other system: hidrosis in 20 (21.7%). After the treatment with sodium dimercaptopropane sulfonate (DMPS), the symptoms were gradually alleviated. Their gastrointestinal, cardiovascular symptoms were alleviated within 2 weeks; neurological symptoms were alleviated within 3 months; kidney damage showed a slower recovery and could be completely alleviated within 6 months. CONCLUSIONS: Because of its diverse clinical symptoms, the mercury poisoning was easy to misdiagnosis and missed diagnosis; therefore the awareness of the disease should be further enhanced. Leaving from the poisoning environment timely and giving appropriate treatment with DMPS will lead to a satisfactory prognosis. PMID- 22093565 TI - A method for simplifying the analysis of traffic accidents injury severity on two lane highways using Bayesian networks. AB - INTRODUCTION: This study describes a method for reducing the number of variables frequently considered in modeling the severity of traffic accidents. The method's efficiency is assessed by constructing Bayesian networks (BN). METHOD: It is based on a two stage selection process. Several variable selection algorithms, commonly used in data mining, are applied in order to select subsets of variables. BNs are built using the selected subsets and their performance is compared with the original BN (with all the variables) using five indicators. The BNs that improve the indicators' values are further analyzed for identifying the most significant variables (accident type, age, atmospheric factors, gender, lighting, number of injured, and occupant involved). A new BN is built using these variables, where the results of the indicators indicate, in most of the cases, a statistically significant improvement with respect to the original BN. CONCLUSIONS: It is possible to reduce the number of variables used to model traffic accidents injury severity through BNs without reducing the performance of the model. IMPACT ON INDUSTRY: The study provides the safety analysts a methodology that could be used to minimize the number of variables used in order to determine efficiently the injury severity of traffic accidents without reducing the performance of the model. PMID- 22093566 TI - Injuries and risk-taking behaviours in Portuguese adolescents: Highlights from the health behaviour in school-aged children survey. AB - AIM: Injuries in adolescence are an important public health problem and a major cause of morbidity and mortality in this age group. This study aimed to determine the behaviour profile associated to risk of injury and the differences between genders, region and ethnic origin. METHODS: A cross-sectional study design of a nationally representative sample of 1581 adolescents of the Portuguese Health Behaviour in School-Aged Children study. RESULTS: An occurrence of one injury related event in the previous year was reported by 21.4% of the respondents and 5.9% referred having more than one injury-related event. Boys reported higher frequency of those events when compared to girls, and non-Portuguese subjects referred higher frequency of events. Scoring higher in violence-related behaviour and psychosomatic complaints was associated to higher chances of referring more than one injury-related event. CONCLUSION: Gender, social background and behaviour profile are factors that seem to influence the risk of injuries. This information should guide those involved in the planning of injuries prevention programs in youth. PMID- 22093567 TI - A process mapping model for calculating indirect costs of workplace accidents. AB - This article follows an earlier one in which four criteria and four bases for the development of an indirect-cost calculation model adapted to the accuracy requirements and time constraints of workplace decision-makers were established. A two-level model for calculating indirect costs using process mapping of the organizational response to a workplace accident is presented. The model is based on data collected in interviews with those employees in charge of occupational health and safety in 10 companies of various sizes in different industry sectors. This model is the first to use process mapping to establish the indirect costs of workplace accidents. The approach allows easy identification of the duration and frequency of actions taken by stakeholders when a workplace accident occurs, facilitates the collection of the information needed to calculate indirect costs and yields a usable, precise result. A simple graphic representation of an organization's accident processes helps the user understand each accident's cost components, allowing the identification and reduction of inefficiencies in the overall process. IMPACT ON INDUSTRY: By facilitating data collection and shortening the time needed to assess indirect costs of workplace accidents, this indirect cost calculation tool is better suited for workplace use than those currently available. PMID- 22093568 TI - What is the potential of trauma registry data to be used for road traffic injury surveillance and informing road safety policy? AB - INTRODUCTION: Information from hospital trauma registries is increasingly being used to support injury surveillance efforts. This research examines the potential of using trauma registry data for road traffic injury surveillance for different types of road users in terms of both the information collected and how representative trauma data are compared to two population-based road traffic injury data collections. METHODS: The three data collections were assessed against recommended variables to be collected for injury surveillance purposes and the representativeness of the distribution of road traffic-related injury data from the trauma registry was compared to hospital admission and road traffic authority data collections. RESULTS: Data from the trauma registry was largely not representative of the distribution of age groups or activities compared to the two population-based collections, but was representative for gender for some road user groups to at least one population-based data collection. CONCLUSIONS: Trauma data could be used to supplement information from population-based data collections to inform road safety efforts. IMPACT ON INDUSTRY: Road safety policy makers should be aware of the potential and the limitations of using trauma registry data for road traffic injury surveillance. PMID- 22093569 TI - Enhancing older driver safety: A driving survey and evaluation of the CarFit program. AB - OBJECTIVE: To evaluate CarFit, an educational program designed to promote optimal alignment of driver with vehicle. METHODS: A driving activity survey was sent to 727 randomly selected participants living in retirement communities. Drivers (n=195) were assigned randomly to CarFit intervention (n=83, M age=78.1) or Comparison (n=112, M age=79.6) groups. After 6months, participants completed a post-test of driving activity and CarFit recommendations. RESULTS: Nonconsenting drivers were older and participated in fewer driving activities. CarFit participation was moderate (71%) with 86% of the participants receiving recommendations. 60% followed the recommendations at the 6-month re-evaluation). The CarFit (67.6%) and Comparison (59.3%) groups reported at least one type of self-regulation of driving activity at baseline. There was no significant change in the driving behaviors at the six-month follow-up. CONCLUSION: CarFit was able to detect addressable opportunities that may contribute to the safety of older drivers. IMPACT ON INDUSTRY: CarFit recommendations may need stronger reinforcement in order to be enacted by a participant. PMID- 22093570 TI - Age and gender differences in conviction and crash occurrence subsequent to being directed to Iowa's driver improvement program. AB - INTRODUCTION: This paper investigates potential gender and age differences in conviction and crash occurrence subsequent to being directed to attend Iowa's Driver Improvement Program (DIP). METHODS: Binary logit models were developed to investigate the factors that influence conviction occurrence after DIP by gender and age. Because of the low crash occurrence subsequent to DIP, association rules were applied to investigate the factors that influence crash occurrence subsequent to DIP, in lieu of econometric models. RESULTS: There were statistical significant differences by driver gender, age, and conviction history in the likelihood of subsequent convictions. However, this paper found no association between DIP outcome, crash history, and crash occurrence. IMPACT ON INDUSTRY: Evaluating the differences in conviction and crash occurrence subsequent to DIP between female and male drivers, and among different age groups can lead to improvements of the effectiveness of DIPs and help to identify low-cost intervention measures, customized based on drivers' gender and age, for improving driving behaviors. PMID- 22093571 TI - Acciphilia on the road: An analysis of severe collisions. AB - INTRODUCTION: Although prior studies of road traffic accidents have found between group differences in risk, little attention has been given to the encounter between drivers involved in severe collisions. METHOD: The present study empirically evaluates two different possible causes of "social accidents," which are defined as collisions between two or more drivers where some faulty social interaction might be assumed, and which are the most prevalent cause of road injuries. The analyses use merged Israeli collision records from 1983 to 2004 with data from two national censuses, thus providing an unprecedented empirical basis to study the social foundations of car accidents. The data are used to adjudicate between two alternative hypotheses: the heterogeneity hypothesis (socially different drivers tend to collide) versus the homogeneity hypothesis (socially similar drivers tend to collide). RESULTS: Multivariate analyses provide preliminary support for the latter hypothesis. Given an accident, there are more collisions among drivers from the same broad educational group, and the factors that influence this correlation are independent of geography. The paper thus leads to the idea that severe collisions reflect a sociological or ecological process that is akin to acciphilia. IMPACT ON INDUSTRY: The preliminary findings suggest that variation between drivers may be preferable to similarity, since apparently there is a greater tendency toward collisions between similar drivers. PMID- 22093572 TI - Severity models of cross-median and rollover crashes on rural divided highways in Pennsylvania. AB - INTRODUCTION: Crossover and rollover crashes in earth-divided, traversable medians on rural divided highways can lead to severe injury outcomes. This study estimated severity models of these two crash types. Vehicle, driver, roadway, and median cross-section design data were factors considered in the models. A unique aspect of the data used to estimate the models were the availability of median cross-slope data, which are not commonly included in roadway inventory data files. METHODS: A binary logit model of cross-median crash severity and a multinomial logit model of rollover crash severity were estimated using five years of data from rural divided highways in Pennsylvania. RESULTS: The highest probability of a fatal or major injury in cross-median and rollover crashes was found to occur in cases when a driver was not wearing a seatbelt. While flatter cross-slopes and narrower medians were associated with more severe cross-median crash outcomes, steeper cross-slopes and narrower medians significantly increased rollover crash severity outcomes. The presence of horizontal curves was associated with increased probabilities of high-severity outcomes in a median rollover crash. IMPACT ON INDUSTRY: Modeling results in this study confirmed that cross-median and median rollover crash severity outcomes are associated with median cross-section design characteristics. Based on the estimated models, it appears that flatter and narrower medians lead to more severe injury outcomes in cross-median crashes. Steeper median cross-slopes and narrower medians were associated with higher probabilities of more severe outcomes in median rollover crashes. The results presented in this study suggest that there is a trade-off between median cross-section design and cross-median and rollover crashes in earth-divided, traversable medians on rural divided highways. While the severity models can be included in a framework to develop design guidance in relation to this trade-off, models of crash frequency should also be considered. PMID- 22093573 TI - Analysis of precipitation-related motor vehicle collision and injury risk using insurance and police record information for Winnipeg, Canada. AB - INTRODUCTION: Police records are the most common source of data used to estimate motor-vehicle collision risks, understand causal or contributing factors, and evaluate the efficacy of interventions. The literature notes concerns about this information citing discrepancies between police reports and other sources of injury occurrence and severity data. The primary objective of the analysis was to assess the adequacy of police reports for an examination of weather-related injury collision risk. METHOD: Analyses of relative risk were carried out using both police records and comprehensive insurance claim data for Winnipeg, Canada over the period 1999-2001. RESULTS AND CONCLUSIONS: Both data sets yielded very similar results-precipitation substantially increases the risk of injury collision (police records: RR 1.76, CI 1.55-2.00; insurance: RR 1.80, CI 1.62 1.99) and risk of injury (police records, RR 1.74, CI 1.55-1.96; insurance, RR 1.69, CI 1.55-1.85) relative to corresponding dry weather control periods. Both rainfall and snowfall were associated with large increases in collisions and injuries. IMPACT ON INDUSTRY: While relative risks are almost identical, over 64% more injury collisions and 74% more injuries were identified using the insurance data, which is an important difference for evaluating absolute risk and exposure. PMID- 22093574 TI - Occupational accidents with ladders in Spain: Risk factors. AB - INTRODUCTION: Occupational accidents suffered by workers in Spain when using ladders were analyzed over a six year period from 2003-2008, during which the total of notified ladder-related accidents amounted to 21,725. METHOD: Different accident-related factors were identified for the purpose of developing a pattern of those factors that had the greatest influence on the seriousness and the fatality of such accidents. Thus, a series of variables were examined such as age and length of service of the injured worker, firm size, the work sector, the injury suffered, and the part of the body that was injured. Since falls is the most frequent and most serious of ladder related occupational accidents, a special analysis of falls was performed. RESULTS: The findings showed that the seriousness of ladder-related accidents increased with the age of the injured worker. Likewise, accidents at places other than the usual workplace were more serious and registered higher fatalities than those that occurred at the usual place of work. CONCLUSIONS: The analysis of falls from ladders established that accidents in smaller-sized firms were of greater seriousness and involved more fatalities than those in larger-sized firms. The investigation also underlined the need for stricter compliance with preliminary safety assessments when working with ladders. PMID- 22093575 TI - The roles and functions of safety professionals in Taiwan: Comparing the perceptions of safety professionals and safety educators. AB - INTRODUCTION: The perspectives of both internal and external members have to be considered when developing safety curricula. This study discusses perceptional differences between safety educators (SEs) and safety professionals (SPs) regarding the function of SPs. The findings will serve as a reference framework for the establishment of core safety competencies and the development of safety curricula for SPs. METHOD: 248 respondents, including both SEs and SPs, completed self-administered questionnaires, which included the 45-item safety function scale (SFS). Nine factors were extracted from the scale using exploratory factor analysis (EFA), namely inspection and research, regulatory tasks, emergency procedures and settlement of damage, management and financial affairs, culture change, problem identification and analysis, developing and implementing solutions, knowledge management, and training and communications. RESULTS: Descriptive statistical results indicated that SPs and SEs hold differing views on the rank of the frequency of safety functions. MANOVA results indicated that SPs' perceptions of developing and implementing solutions, training and communications, inspection and research, and management and financial affairs were significantly higher than that of SEs. On the other hand, SE's perceptions regarding participation in regulatory tasks were significantly higher than those of SPs. Based on these results, the author suggests that a clear communication channel should be established between universities and industry to reduce the gap between the perceptions of SEs and SPs. IMPACT ON INDUSTRY: The results of the study are statistically and practically significant. In addition to serving as a reference for the development of safety curricula, the results are also conducive to the establishment of SP roles and functions. Ultimately the development of more suitable safety curricula would open up employment competition for students who graduate from safety-related programs. SPs, on the other hand, can correctly recognize their roles and functions so as to realize the safety expectations invested in them by organizations. PMID- 22093576 TI - Disparities in the prevalence of smoke alarms in U.S. households: Conclusions drawn from published case studies. AB - INTRODUCTION: Deaths from fires and burns are a leading cause of fatal home injury in the United States. Smoke alarms are one of the most effective interventions to prevent residential fire deaths. Nationwide, more than 95% of homes are estimated to have at least one smoke alarm. There is evidence that homes at highest risk of fire deaths lag behind national averages in smoke alarm use and maintenance. METHOD: We compiled a comprehensive list of published studies that focus on smoke alarm prevalence in high-risk homes. Our findings show that there are substantial gaps in both smoke alarm presence and functional status between high-risk homes and national average estimates. CONCLUSIONS: To save more lives, improved efforts are needed to reduce the disparity in smoke alarm prevalence and functional use in the United States. PMID- 22093577 TI - The nursing contribution to chronic disease management: a case of public expectation? Qualitative findings from a multiple case study design in England and Wales. AB - BACKGROUND: The global response to the rise in prevalence of chronic disease is a focus on the way services are managed and delivered, in which nurses are seen as central in shaping patient experience. However, there is relatively little known on how patients perceive the changes to service delivery envisaged by chronic care models. OBJECTIVES: The PEARLE project aimed to explore, identify and characterise the origins, processes and outcomes of effective chronic disease management models and the nursing contributions to the models. Design, settings and participants Case study design of seven sites in England and Wales ensuring a range of chronic disease management models. Participants included over ninety patients and family carers ranging in age from children to older people with conditions such as diabetes, respiratory disease, epilepsy, or coronary heart disease. METHODS: Semi-structured interviews with patients and family carers. Focus groups were conducted with adolescents and children. A whole systems approach guided data collection and data were thematically analysed. RESULTS: Despite nurses' role and skill development and the shift away from the acute care model, the results suggested that patients had a persisting belief in the monopoly of expertise continuing to exist in the acute care setting. Patients were more satisfied if they saw the nurse as diagnostician, prescriber and medical manager of the condition. Patients were less satisfied when they had been transferred from an established doctor-led to nurse-led service. While nurses within the study were highly skilled, patient perception was guided by the familiar rather than most appropriate service delivery. Most patients saw chronic disease management as a medicalised approach and the nursing contribution was most valued when emulating it. CONCLUSIONS: Patients' preferences and expectations of chronic disease management were framed by a strongly biomedical discourse. Perceptions of nurse-led chronic disease management were often shaped by what was previously familiar to the patient. At a strategic level, autonomous nursing practice requires support and further promotion to wider society if there is to be a shift in societal expectation and trust in the nurse's role in chronic disease management. PMID- 22093578 TI - Evolutionary and functional insights into Leishmania META1: evidence for lateral gene transfer and a role for META1 in secretion. AB - BACKGROUND: Leishmania META1 has for long been a candidate molecule for involvement in virulence: META1 transcript and protein are up-regulated in metacyclic Leishmania. Yet, how META1 contributes to virulence remains unclear. We sought insights into the possible functions of META1 by studying its evolutionary origins. RESULTS: Using multiple criteria including sequence similarity, nucleotide composition, phylogenetic analysis and selection pressure on gene sequence, we present evidence that META1 originated in trypanosomatids as a result of a lateral gene transfer of a bacterial heat-inducible protein, HslJ. Furthermore, within the Leishmania genome, META1 sequence is under negative selection pressure against change/substitution. Using homology modeling of Leishmania META1 based on solved NMR structure of HslJ, we show that META1 and HslJ share a similar structural fold. The best hit for other proteins with similar fold is MxiM, a protein involved in the type III secretion system in Shigella. The striking structural similarity shared by META1, HslJ and MxiM suggests a possibility of shared functions. Upon structural superposition with MxiM, we have observed a putative hydrophobic cavity in META1. Mutagenesis of select hydrophobic residues in this cavity affects the secretion of the secreted acid phosphatase (SAP), indicating META1's involvement in secretory processes in Leishmania. CONCLUSIONS: Overall, this work uses an evolutionary biology approach, 3D-modeling and site-directed mutagenesis to arrive at new insights into functions of Leishmania META1. PMID- 22093579 TI - Safety and effectiveness of adalimumab in a clinical setting that reflects Canadian standard of care for the treatment of rheumatoid arthritis (RA): results from the CanACT study. AB - BACKGROUND: This multicenter, open-label, prospective, single cohort study evaluated the effectiveness and safety of adalimumab in a clinical setting reflecting the Canadian standard of care for the treatment of patients with rheumatoid arthritis (RA). METHODS: Patients >= 18 years of age with a history of active RA >= 3 months and fulfilling Canadian requirements for biological therapy received adalimumab 40 mg subcutaneously every other week for 12 weeks. Pre-study DMARD treatment regimens, corticosteroids, or NSAIDs were allowed throughout the study. The primary effectiveness outcome measure was the mean change in 28-joint disease activity score (DAS28) from baseline to Week 12. Secondary measures included the proportion of patients achieving joint remission (DAS28 < 2.6) and low-disease activity (DAS28 < 3.2) at Week 12, and European League Against Rheumatism (EULAR: moderate and good) and American College of Rheumatology (ACR: ACR20, 50, and 70) responses, as well as responses in ACR core components at Weeks 4, 8, and 12. Subgroup analysis included a comparison of patients naive to biological DMARD (BDMARD) therapy versus BDMARD-experienced patients. Safety was assessed in terms of adverse and serious adverse events. RESULTS: A total of 879 patients (mean disease duration > 12 years) were enrolled; 772 (87.9%) completed the 12-week period. Adalimumab treatment was associated with rapid and sustained improvements in the signs and symptoms of RA. Significant improvements in mean DAS28 score were observed as early as Week 4. After 12 weeks of adalimumab treatment, 15.3% and 28.9% of patients achieved clinical remission and low disease activity, respectively. Similarly, significant improvements in ACR core components were observed as early as Week 4, with continued improvements occurring through 12 weeks. Patients naive to BDMARD therapy demonstrated numerically greater clinical responses when compared with patients who had experienced prior BDMARD therapy, although both subgroups were associated with significant improvements from baseline. The rates and types of adverse events, as well as the results of laboratory measures, demonstrated that adalimumab was generally safe and well-tolerated. CONCLUSIONS: This study demonstrated that, under conditions reflective of the normal clinical practice in Canada, adalimumab is an effective and safe treatment for patients with RA. TRIAL REGISTRATION: NCT00649545. PMID- 22093580 TI - Clinical implications of novel mutations in epigenetic modifiers in AML. AB - The studies highlighted in this article suggest that mutations in TET2 mutations may impart adverse outcome in patients with CN-AML, whereas mutations in DNMT3a may have adverse implications in a broader set of patients with AML. The data with IDH enzyme mutations are less clear, in that individual IDH1 and IDH2 mutations may have different clinical effects and the data so far have not suggested a uniform effect on outcome. Despite the exciting data indicating that mutational testing for these alterations may be clinically useful, several challenges to understanding their clinical relevance remain. First, patients may simultaneously have mutations in multiple genes described in this article (FLT3, NPM1, CEBPa, DNMT3a, IDH1/2, or TET2), and in additional genes not mentioned earlier (Ras,47 PTEN,48 PHF6,49 ASXL1,15 and RUNX145). Furthermore, comprehensive sequencing studies of well-annotated, homogeneously treated patient cohorts are needed to understand the clinical implications of integrated mutational profiling in AML. An additional challenge to using mutational analysis for TET2 and DNMT3a in clinical use is identifying a means for rapid molecular testing of these mutations. This challenge may be met by the use of non-polymerase chain reaction based methods of target enrichment, such as hybrid capture, followed by next generation sequencing technologies. Moreover, clinical studies evaluating the biochemical consequences of mutations in some of these genes (eg, production of 2 HG in bodily fluids from patients with IDH-mutant AML or increased hydroxymethylcytosine levels in pretreatment blast DNA in patients with TET2/IDH mutant AML) may also prove to be useful in identifying biomarkers. Alternatively, protein-based technologies such as immunohistochemistry or mass spectrometry may be used in the clinical setting to detect the mutant proteins or loss of expression of specific proteins in patients with mutations. An additional area of importance highlighted by these discoveries is the increasing realization that several of these genes encode enzymes or result in alterations in enzymatic activities, which may represent novel, tractable therapeutic targets for patients with AML. This finding may hopefully lead to the development of novel targeted therapeutics for patients with specific genetic alterations in AML. This development may be occurring now with the advent of DOT1L-targeted therapy for leukemic cells with translocations involving MLL1.50,51 Studies to identify whether the neomorphic enzymatic activity of IDH1/2 mutations may be targetable or if the downstream effects of TET2 mutations can be targeted are ongoing and may lead to the development of rational epigenetic therapies that improve outcomes for patients with AML. PMID- 22093581 TI - Diagnostic and prognostic value of cytogenetics in acute myeloid leukemia. AB - The last 4 decades have seen major advances in understanding the genetic basis of acute myeloid leukemia (AML), and substantial improvements in survival of children and young adults with the disease. A key step forward was the discovery that AML cells harbor recurring cytogenetic abnormalities. The identification of the genes involved in chromosomal rearrangements has provided insights into the regulation of normal hematopoiesis and how disruption of key transcription factors and epigenetic modulators promote leukemic transformation. Cytogenetics has been widely adopted to provide the framework for development of risk stratified treatment approaches to patient management. PMID- 22093582 TI - Prognostic factors in adult acute leukemia. AB - The prognostic factors in acute leukemia have undergone a major change over the past decade and are likely to be further refined in the coming years. While age is the single most important prognostic factor in both AML and in ALL, recurring cytogenetic abnormalities and molecular markers have become crucial for the prognosis of patients and for new directions in the development of targeted therapies. No less important is the development of a personalized approach for therapy as determined by the response to therapy using increasingly sensitive technologies. The assessment of MRD is rapidly superseding other prognostic factors in ALL and, somewhat lacking behind, coming into its own in AML. The next decade should see further refinement of response-driven prognostication, to include epigenetics as well as pharmacogenetics and pharmacodynamics of individual drugs used and the responses to them. It is hoped that these refinements and better predictors of response will also lead to a significantly improved overall outcome of patients with both AML and ALL. PMID- 22093583 TI - Induction and postremission strategies in acute myeloid leukemia: state of the art and future directions. AB - Although the past decade has brought improvements in the treatment of AML, particularly for younger individuals, most patients succumb to the disease. With current induction therapy, most patients achieve remission, but the optimal strategy for post-remission therapy is unclear. Refinements to risk classification systems that incorporate additional molecular markers may better guide physicians in recommendations for postremission therapy. The prognosis for older patients with AML remains uniformly poor, because only a minority can benefit from intensive chemotherapy and novel HCT strategies. Despite active investigation, no standard of care has emerged for patients who are not suitable candidates for standard induction therapy. The development of less toxic, more effective therapies for this population is sorely needed. Advances in molecular genetics, immunology, and the biology of normal and malignant hematopoiesis pathogenesis have led to an improved understanding of the pathogenesis of AML and to the discovery of potential therapeutic targets. Until a greater proportion of individuals with AML attain long-term survival, patients should routinely be referred to cancer centers and enrolled in investigational studies. PMID- 22093585 TI - Oddballs: acute leukemias of mixed phenotype and ambiguous origin. AB - From the standpoint of the hematopathologist, attempts to dissect the immunophenotype and other lineage-defining characteristics of the puzzling group of acute leukemias of ambiguous origin have prompted considerable discussion and debate. For clinicians, however, such definitions, although academically interesting, as yet give relatively little insight into the most appropriate therapy, and patients with MPAL continue to do poorly compared with more typical AML or ALL cases. The most recent WHO 2008 MPAL definitions are provocative, but represent a major change from the previous EGIL BAL classification, and the clinical relevance of this change has yet to be established. Only further insight from the molecular biology laboratory can help define the true cell of origin and molecular drivers of ambiguous leukemias. New molecular information will allow clinicians and pathologists to refine classification of these challenging entities, and most importantly, should permit improved treatment for patients. PMID- 22093584 TI - Curing all patients with acute promyelocytic leukemia: are we there yet? AB - The introduction of all-trans retinoic acid to anthracycline-based chemotherapy has revolutionized the prognosis of patients with acute promyelocytic leukemia (APL). The introduction of arsenic trioxide enabled the therapeutic approach of rationally targeted frontline protocols with minimal or no traditional cytotoxic chemotherapy and without compromise of previously established outstanding outcomes with anthracycline-based regimens. Although most of the current investigative efforts in APL are focused on developing potentially curative therapy without the exposure to toxicities and risks of DNA-disrupting agents, the cure rate can further be increased by implementing meticulous supportive care strategies that counter early coagulopathy-related deaths. PMID- 22093586 TI - Current therapeutic strategies in adult acute lymphoblastic leukemia. AB - Approximately half of all adults with acute lymphoblastic leukemia now survive long term. This article summarizes the current approaches to treating acute lymphoblastic leukemia in adults, with a focus on a pragmatic approach to decision making. Coupled with a particularly punishing and often complex combination chemotherapy treatment regimen, treatment-related morbidity and mortality are frequent, and this article focuses on these situations. The field will change significantly over the next few years with many ongoing clinical studies and molecular insights which will be translated into providing prognostic information and novel therapeutic targets. PMID- 22093588 TI - Novel therapeutic approaches for acute lymphoblastic leukemia. AB - Therapy for ALL in adults remains a tremendous challenge for clinicians. The use of pediatric-intensive regimens in young and middle-aged adults shows promise in improving outcomes. The addition of monoclonal antibody therapy to chemotherapy appears to hold great promise in lessening relapse rates. The anti-CD20 antibody, rituximab, which has been of such benefit in patients with non-Hodgkin lymphoma, now seems poised to bring significant benefit to adults with ALL. Other monoclonal antibody approaches are in earlier stages of development, but will likely be of significant benefit. The BiTE antibody, blinatumomab, represents an exciting new approach in this arena. As new molecular abnormalities are identified in ALL, these will certainly become new targets for drug development. The increasing use of MRD testing by molecular or flow cytometric techniques will also be invaluable in further refining prognostication in ALL in helping with the selection of patients most likely to benefit from BMT. Several new small molecules and chemotherapeutic agents will, it is hoped, also find a niche in the therapy for ALL. Early examples including NOTCH1 inhibitors; hypomethylating agents such as decitabine, folic acid, antagonists, flavopiridol, bortezomib, and mTOR inhibitors will all hopefully find a role in the therapy for this challenging disorder. Although many challenges remain, there is hope that the therapy for adults with ALL can make significant progress in the next few years, in comparison with the relative plateau that has been experienced over the last several decades. PMID- 22093587 TI - Cellular therapies in acute lymphoblastic leukemia. AB - ALL remains a difficult disease to treat. In the adult setting, most patients will ultimately die of their disease, whereas in the pediatric setting, relapsed and refractory disease remains a therapeutic challenge. Cellular therapy through allo-HSCT remains an option for these patients, and recent advances in alternative forms of allo-HSCT, including unrelated donor transplants, UCB transplants, and haploidentical transplants, have expanded the numbers of patients eligible for allo-HSCT but have not improved outcomes when compared with HLA-matched related allo-HSCTs. In light of this persistent failure, several novel adoptive cellular approaches are being investigated to treat patients with ALL. The use of enriched WT-1-specific donor T cells to treat patients with ALL is currently under investigation in phase I trials at several centers. Treatment of ALL with genetically modified T cells targeted to the CD19 antigen through the expression of a CD19-specific CAR also have entered phase I clinical trials at several centers. Similarly, a clinical trial treating patients with ALL with genetically modified NK cells targeted to the CD19 antigen has recently opened for accrual. Collectively, these ongoing and anticipated trials provide a promising role for adoptive cellular therapies in the treatment of ALL. What remains to be seen is whether this promise will either translate into improved outcomes for these patients or provide significant insights on which to design second-generation adoptive cell therapeutic clinical trials for ALL in the future. PMID- 22093590 TI - Acute leukemias. PMID- 22093589 TI - Novel transplant strategies in adults with acute leukemia. AB - Autologous and allogeneic hematopoietic cell transplantation (HCT) is regularly used as a curative treatment option for patients with various disorders, including acute leukemia in adults. The past decade has witnessed dramatic improvements in the reduction of treatment-related mortality (TRM), in part attributable to improved supportive care but also due to better graft selection and donor-to-recipient matching regimens, and the emergence of reduced-intensity conditioning in place of myeloablative conditioning. Despite these advances, HCT remains plagued by the risk of relapse or failure due to graft-versus-host disease, infectious complications, and TRM. This article reviews new approaches that may improve overall patient outcome. PMID- 22093591 TI - The evaluation of creatinine clearance, estimated glomerular filtration rate and serum creatinine in predicting contrast-induced acute kidney injury among patients undergoing percutaneous coronary intervention. AB - PURPOSE: The purpose of the study was to compare creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR) and serum creatinine (SCr) in predicting contrast-induced acute kidney injury (CI-AKI), dialysis and death following percutaneous coronary intervention (PCI). METHODS AND MATERIALS: Data were prospectively collected on 7759 consecutive patients within the Dartmouth Dynamic Registry undergoing PCI between January 1, 2000, and December 31, 2006. Renal function was measured at baseline and within 48 h after PCI using three methods: CrCl using the Cockcroft-Gault equation, eGFR using the abbreviated Modification of Diet in Renal Disease equation and SCr. We compared CrCl, eGFR and SCr in predicting CI-AKI, post-PCI dialysis-dependent renal failure and in hospital mortality. Areas under the receiver operating characteristic curve (ROC) were calculated using logistic regression and tested for equality. RESULTS: On univariable analysis, CrCl [ROC: 0.69; 95% confidence interval (CI): 0.67-0.72] predicted CI-AKI better than eGFR (ROC: 0.67; 95% CI: 0.64-0.70) (P=.013) and SCr (ROC: 0.64; 95% CI: 0.61-0.67) (P<.001). Creatinine clearance (ROC: 0.73; 95% CI: 0.69-0.77) and eGFR (ROC: 0.70; 95% CI: 0.65-0.74) outperformed SCr for predicting in-hospital mortality. On multivariable analysis, CrCl (ROC: 0.77; 95% CI: 0.75-0.80), SCr (ROC: 0.78; 95% CI: 0.76-0.80) and eGFR (ROC: 0.77; 95% CI: 0.75-0.80) predicted CI-AKI well. Creatinine clearance (ROC: 0.88; 95% CI: 0.85 0.90) and eGFR (ROC: 0.87; 95% CI: 0.85-0.90) were strong independent predictors of in-hospital mortality. CONCLUSIONS: Creatinine clearance, eGFR and SCr predict CI-AKI equally well. Creatinine clearance and eGFR are strong independent predictors of in-hospital mortality. PMID- 22093592 TI - Management of acute left main obstruction after transcatheter aortic valve replacement: the "tunnel technique". AB - Two cases of acute left main (LM) obstruction complicating transcatheter aortic valve replacement (TAVR) and their management are reported. TAVR with a self expandable transcatheter aortic prosthesis was performed for treating severe aortic stenosis with small aortic root and severe aortic regurgitation of a degenerated stentless bioprosthesis, respectively. Left main coronary obstruction occurred at a different time from the index procedure. A novel stent-based angioplasty treatment, denominated "the tunnel technique," was successfully applied in both cases and herein described. PMID- 22093593 TI - Improving safety outcomes in the epilepsy monitoring unit. AB - Long term video electroencephalography (EEG) in epilepsy monitoring units (EMU) is used to diagnose and treat patients with epilepsy. Injury occurs in the EMU, including reports of death. No standardized patient safety protocols exist. Our objective is to determine the frequency and contributing factors to injury in the EMU. We reviewed medical records and video EEG of patients with epilepsy admitted to our EMU from December 1, 2008 to June 1, 2009. Data was collected on seizure type, onset, length, and frequency. Seizure related falls, injury, and adverse events were recorded. Data regarding the physical environment and treatment during seizures were analyzed too. 20 patients with 170 seizures were collected. Of the 170 total seizures captured, only 1 injury (0.6%) and 6 falls occurred (3.5%). 5 of the 6 falls were related to patients being ambulatory. No seizures resulted in prolonged stay. Of the 170 seizures captured, other adverse events included 1 status epilepticus (0.6%), 2 postictal aggression (1.2%), 4 objects in mouth (2.4%), 14 ambulatory at seizure onset (8.2%) and 5 postictal ambulation from bed (2.9%). Staff responded to 69 out of 170 seizures (40.6%). Of the 101 seizures without staff response, 57 seizures were electrographic without seizure detection software or push button activation. Falls and adverse events that can lead to injury occur in the EMU, yet the degree of actual injury is minimal. To improve safety outcomes, standardized protocols with appropriate outlined nursing care and procedures for continuous monitoring of patients by staff need to be employed. PMID- 22093594 TI - Hemodialysis international. PMID- 22093595 TI - What is good about PD + HD combined therapy. AB - It is known that beta(2) -microglobulin (beta(2) -MG) concentration in peritoneal dialysis (PD) patients is inversely correlated to the residual renal function (RRF). With decreasing RRF, some PD patients may necessarily be treated with hemodialysis (HD) once a week, not only for removing excess water and small solutes, but also for removing much larger solutes such as beta(2) -MG. In this study, a kinetic model allowed us to show what is good about PD + HD combined therapy in long-term PD patients. A mathematical model was established based on a classic compartment theory for clinical use. Model validations were made by comparing calculated results with clinical data in order to specify what was good about PD + HD combined therapy (5-day PD + 1-HD/week). Time-averaged concentration (TAC) for urea and creatinine decreased by 20% on the average by introducing PD+HD combined therapy no matter which dialyzers were used. TAC for beta(2) -MG in PD+HD combined therapy, however, was strongly dependent upon the dialyzer clearance, and when a low flux dialyzer (clearance for beta(2) -MG = 10 mL/min under Q(B) = 200, Q(D) = 500 mL/min) was used, pre-dialysis beta(2) -MG concentration may increase. Use of super high-flux dialyzers (clearance for beta(2) -MG = 60 mL/min under the same conditions) should greatly reduce the beta(2) -MG concentration from 30 to 8 mg/L in 4-hr treatment. Then, when PD+HD combined therapy is introduced to a PD patient with diminishing RRF, use of super high-flux dialyzers may be strongly recommended in order not to increase concentrations of pre-dialysis beta(2) -MG and/or even greater solutes. Use of super high-flux dialyzers is a key to the success of PD+HD combined therapy that could prevent concentrations of large solutes from increasing. PMID- 22093596 TI - Use of ionic dialysance to calculate Kt/V in pediatric hemodialysis. AB - Online clearance (OLC) monitor measures conductivity difference between dialysate entering and leaving the dialyser. Derived ionic dialysance (ID) represents effective urea clearance from which Kt/V is calculated, allowing Kt/V monitoring at every treatment without blood sampling. We tested ID accuracy in children and provide recommendations for its use. Using Fresenius machines 2008 K with built in OLC monitors, we studied 45 hemodialysis (HD) sessions and 168 calculated Kt/V results in 11 patients. Urea distribution volume (V), needed to calculate Kt/V from ID, was estimated using three methods: Mellits and Cheek (MC), KDOQI recommended total body water nomograms (TBWN) and OLC-derived independent from tested HD sessions. Reference spKt/V from pre- and post-HD BUN (Daugirdas) was compared with Kt/V calculated from ID using three different estimated V's. ID was accurate in calculating Kt/V in children when V derived from OLC was used (P = 0.42), with absolute error 0.14 +/- 0.12. If TBWN-derived V was used, Kt/V was consistently underestimated by 0.32 +/- 0.22. TBWN-derived V can still be recommended for use with OLC for monitoring trend in Kt/V, if underestimation of spKt/V of average 0.3 is accounted for. MC-derived V results in even greater underestimation of spKt/V and therefore cannot be recommended for use with OLC. PMID- 22093597 TI - Sudden cardiac arrest and sudden cardiac death on dialysis: Epidemiology, evaluation, treatment, and prevention. AB - Sudden cardiac death is the most common cause of death in dialysis patients and is usually preceded by sudden cardiac arrest due to ventricular tachycardia or ventricular fibrillation. A variety of risk factors have been identified that predispose the sudden cardiac arrest and sudden cardiac death in dialysis patients. Primary prevention of sudden cardiac arrest in dialysis patients may be accomplished by avoiding the use of low potassium dialysate. Pharmacotherapy with beta-blockers angiotensin converting enzyme inhibitors and angiotensin receptor blockers and use of implantable cardioverter defibrillators (ICDs) may also prevent sudden cardiac arrest and sudden cardiac death in high-risk dialysis patients. Secondary prevention of sudden cardiac death may be accomplished by similar pharmacotherapy and by the use of ICDs. Indications for ICD use in dialysis patients are similar to those for nondialysis patients; however, survival rates following ICD implantation in dialysis patients are substantially lower than in non-dialysis patients. PMID- 22093598 TI - Percutaneous coronary intervention versus coronary artery bypass graft in chronic kidney disease: Optimal treatment options. AB - Chronic kidney disease (CKD) is ubiquitous in the world and may eventually progress to end-stage renal disease. CKD is associated with a greater risk of coronary artery disease (CAD) which is the leading cause of mortality in this population. Current invasive treatment options include percutaneous coronary intervention or coronary artery bypass graft. We performed a PubMed search to ascertain the optimal treatment for coronary artery disease in CKD. Our review of the current literature supports the superiority of coronary artery bypass grafting which reduces repeat revascularizations, improves angina symptoms, and increases long-term survival. PMID- 22093599 TI - Using dialysis machine technology to reduce intradialytic hypotension. AB - Intradialytic hypotension remains the most frequent complication associated with routine outpatient hemodialysis. Although increasing dialysis frequency and also lengthening dialysis session duration can reduce the risk of intradialytic hypotension, in practice, these options are limited to a small minority of dialysis patients. To help reduce intradialytic hypotension, a number of technological developments have been incorporated into the hemodialysis machine, based around relative blood volume monitoring, an indirect assessment of plasma volume. Further developments based on so called "fuzzy" logic feedback systems designed to adjust either or both the ultrafiltration rate and dialyzate sodium concentration according to relative changes in plasma volume. In addition, cooling and dissipation of the heat generated during dialysis also reduces the risk of intradialytic hypotension, and this can be regulated by cooling of the dialyzate using thermal control systems. In addition, convective therapies, such as online hemodialfiltration, have also been reported to reduce the frequency of intradialytic hypotension; whether this effect is simply due to increased cooling remains to be determined. Although all these developments have been reported to reduce the frequency of serious intradialytic hypotensive episodes, they have not been able to totally abolish hypotension, as they can not alone compensate for excessive weight gains and consequent excessive ultrafiltration requirements. Thus, in addition to the advances in hemodialysis machine technology designed to reduce intradialytic hypotension, attention also needs to be focused on reducing interdialytic weight gains, so reducing ultrafiltration requirement. PMID- 22093600 TI - Optimization of heparin anticoagulation for hemodialysis. AB - Unfractionated heparin remains the most commonly used anticoagulant for extracorporeal therapies worldwide due to cost, years of clinical experience showing effectiveness and safety for outpatient hemodialysis. Most centers administer unfractionated heparin as an initial bolus followed by a constant infusion, which is then stopped prior to the end of the dialysis session. Although the anticoagulant effect of heparin can be monitored at the bedside, most centers take a pragmatic stance for routine outpatient hemodialysis, and adjust bolus doses and infusion rates based on visual inspection of the dialyzer header and venous air detector chamber for clots, and stop the heparin infusion based on the time taken for needle puncture sites to stop bleeding at the end of the hemodialysis session. Heparin is negatively charged and can bind to plasma proteins, leukocytes, and plastic. As such, it is important to achieve adequate mixing of heparin with blood to optimize anticoagulation within the extracorporeal circuit, by administering an intravenous bolus a few minutes prior to connecting the patient to the circuit and ensuring thorough mixing of the heparin infusion. PMID- 22093601 TI - Role of dialysis technology in the removal of uremic toxins. AB - Traditionally, the amount of hemodialysis prescribed for a patient has been based on urea clearance, as urea is not only retained in patients with chronic kidney disease, but also readily measurable, by reliable and inexpensive assays. More recently, other retained solutes, phosphate, beta2 microglobulin, and latterly p cresol have been reported to be associated with increased risk of mortality in hemodialysis patients. As such, developments in dialysis practice that would result in greater clearance of water-soluble middle-sized toxins and also protein bound and/or organic solutes are being studied. Although session time is a key factor, switching from low flux to dialyzers with larger pores, the addition of convective transport with hemodiafiltration can help increase phosphate and beta2 microglobulin clearances. Adsorption techniques can increase the clearance of organic and protein bound toxins either directly or indirectly by regenerating dialysate and ultrafiltrates. PMID- 22093602 TI - Postprostatectomy seizures: A case report. AB - A 75-year-old Caucasian male presented with generalized seizures half-hour post transurethral resection of the prostate surgery. The intra-operative course was complicated by perforation of the posterior wall of the bladder neck during a difficult Foley catheter placement. This resulted in intraperitoneal extravasation of the glycine containing bladder irrigation fluid. An emergent laparotomy was performed, and 3.5-4 L of fluid was drained from the peritoneal cavity. Postoperative course was complicated by two seizures within a short interval. Patient developed profound hyponatremia (Na of 109 mEq/L). However, measured serum osmolality was normal (283 mOsm/kg). The serum osmolality remained relatively stable, indicating that the absorbed glycine and its metabolites remained osmotically active in the intravascular space (until they were dialyzed as mentioned later), making the hyponatremia less pernicious and an unlikely cause of patient's symptoms. The encephalopathy and seizures were ascribed to accumulation of toxic metabolites of glycine, especially ammonia (serum level 1261 mcmol/L). During a complicated postoperative period, patient developed oligo anuric renal failure, and was started on slow low-efficiency dialysis for 8 hours resulting in rapid lowering of serum ammonia levels and glycine with reversal of encephalopathy including seizures. There was no recurrence of encephalopathy, seizures, or metabolic acidosis. Although rare, glycine toxicity may be life threatening. The pathophysiology, need for early detection and the role of early use of renal replacement therapy in acute glycine toxicity is discussed below. PMID- 22093603 TI - A successful term pregnancy using in-center intensive quotidian hemodialysis. AB - A 30-year-old woman with stage V chronic kidney disease presented at 7 weeks gestation. She had no uremic symptoms; however, blood urea nitrogen (BUN) was 33.6 mg/dL. Because of the well-established negative relationship between BUN and fetal outcomes, dialysis was initiated with a nocturnal home hemodialysis (NHD) like prescription performed in-center for logistical reasons. She received 36 hours per week of dialysis. Following the initiation of renal replacement therapy, the predialysis BUN was within the normal physiologic range. The patient had an uncomplicated pregnancy with delivery of a healthy 3000 g infant at 39 weeks gestation. This case adds to the growing literature that supports more intensive dialysis in the pregnant women than was previously recommended. This dose of dialysis should be offered to women in an in-center setting if nocturnal home hemodialysis is not available or feasible. PMID- 22093604 TI - Medulloblastoma presenting as dialysis disequilibrium syndrome. AB - Dialysis disequilibrium syndrome (DDS) is a central nervous system disorder that occurs during or after hemodialysis. This is caused by brain edema that manifests as neurological symptoms that include headache, emesis, nausea, blurring of vision, disturbed consciousness, tremors and seizures, and in severe cases, death. The incidence of DDS is very high among patients with preexisting neurological diseases. There has been much debate about the origin of DDS. We report a case of DDS, as presenting syndrome of a medulloblastoma in a child aged 5 years, and discuss the pathogenesis and the possible role of DDS for an earlier detection of occult brain lesions in dialyzed patients. PMID- 22093605 TI - Metformin intoxication requiring dialysis. AB - Metformin (MTF) is one of the most common oral agents used to treat diabetes mellitus. Intoxication is associated with lactic acidosis and has significant clinical consequences. We report 12 cases requiring dialytic intervention. Twelve patients were analyzed from 2005 to 2010; 10 of these patients were treated with dialysis. Conventional hemodialysis (HD) and continuous veno-venous hemodialysis treatments with bicarbonate dialysis were used, and the results were presented as mean and standard deviation. The results are as follows: 33% of the patients were male, hospital stay was 9.3 (+/- 12) days, average MTF dose 1.7 g/day, mortality was 25%. Baseline glomerular filtration rate for these patients was 51.5 mL/min, with an average age of 64 (+/- 11) years. On presentation, all had acute kidney injury with blood urea nitrogen/creatinine 75 (+/- 30)/8.1 (+/- 3.7) mg/dL, lactic acid 12.4 (+/- 8.1) mmol/L, pH 7.04 (+/- 0.19), bicarbonate 7.2 (+/- 4.5) mmol/L. Metformin level was 25 (+/- 17) ug/mL; anion gap was 28 (+/- 9), and serum potassium was 5.4 (+/- 1.3) mEq/L. Seventy percent of patients were treated with conventional HD. Patients required 4 (+/- 5) dialysis treatments at blood flow QB 330 (+/- 53), dialysis flow QD 571 (+/- 111) for 305 (+/- 122) minutes. Postdialysis, the acidosis parameters improved: bicarbonate 19.2 (+/- 4.1) mmol/L, lactic acid 6 (+/- 4) mmol/L and MTF levels decreased 8.9 (+/- 5.7) ug/mL. Metformin percentage removal was calculated to be 60% (+/- 24). No difference was found between HD and continous veno-venous hemodialysis. The only difference between survivors was the age 53 (+/- 7) vs. 78 (+/- 10) (P < 0.05). Metformin toxicity is a serious clinical condition and causes severe lactic acidosis and significant mortality. Hemodialysis is an efficient method to treat MTF intoxication and correct the metabolic abnormalities. PMID- 22093606 TI - A simple method to estimate phosphorus mobilization in hemodialysis using only predialytic and postdialytic blood samples. AB - We have recently developed a pseudo one-compartment model to describe intradialytic and postdialytic rebound kinetics of plasma phosphorus. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter; the phosphorus mobilization clearance (K(M) ). In this work, we propose a simple method to estimate K(M) from predialytic and postdialytic plasma phosphorus concentrations. Clinical data were collected from 22 chronic hemodialysis patients that underwent a 4-hour treatment session. A simple algebraic equation was derived from the pseudo one-compartment model to determine K(M) from predialytic and postdialytic plasma phosphorus concentrations. K(M) values computed using this equation were compared with values obtained from nonlinear regression of the full kinetic model to frequent intradialytic and postdialytic measurements of plasma phosphorus concentrations. There was good agreement between K(M) values (concordance correlation coefficient of 0.94) obtained from the simple method (105 +/- 52 mL/min, mean +/- SD) and from the full model (99 +/- 47 mL/min). The 95% confidence interval for the difference between estimated K(M) values was -26 to 36 mL/min. The proposed simple method requires the use of only predialytic and postdialytic blood samples to estimate patient specific K(M) ; this approach may allow easy clinical evaluation of phosphorus kinetics in hemodialysis patients. PMID- 22093607 TI - Genetic factors associated with the presence and progression of nonalcoholic fatty liver disease: a narrative review. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Whereas insulin resistance and obesity are considered major risk factors for the development and progression of NAFLD, the genetic underpinnings are unclear. Before 2008, candidate gene studies based on prior knowledge of pathophysiology of fatty liver yielded conflicting results. In 2008, Romeo et al. published the first genome wide association study and reported the strongest genetic signal for the presence of fatty liver (PNPLA3, patatin-like phospholipase domain containing 3; rs738409). Since then, two additional genome wide scans were published and identified 9 additional genetic variants. Whereas these results shed light into the understanding of the genetics of NAFLD, most of associations have not been replicated in independent samples and, therefore, remain undetermined the significance of these findings. This review aims to summarize the understanding of genetic epidemiology of NAFLD and highlights the gaps in knowledge. PMID- 22093608 TI - Glycoconjugates in New World species of Leishmania: polymorphisms in lipophosphoglycan and glycoinositolphospholipids and interaction with hosts. AB - BACKGROUND: Protozoan parasites of the genus Leishmania cause a number of important diseases in humans and undergo a complex life cycle, alternating between a sand fly vector and vertebrate hosts. The parasites have a remarkable capacity to avoid destruction in which surface molecules are determinant for survival. Amongst the many surface molecules of Leishmania, the glycoconjugates are known to play a central role in host-parasite interactions and are the focus of this review. SCOPE OF THE REVIEW: The most abundant and best studied glycoconjugates are the Lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs). This review summarizes the main studies on structure and biological functions of these molecules in New World Leishmania species. MAJOR CONCLUSIONS: LPG and GIPLs are complex molecules that display inter- and intraspecies polymorphisms. They are key elements for survival inside the vector and to modulate the vertebrate immune response during infection. GENERAL SIGNIFICANCE: Most of the studies on glycoconjugates focused on Old World Leishmania species. Here, it is reported some of the studies involving New World species and their biological significance on host-parasite interaction. This article is part of a Special Issue entitled Glycoproteomics. PMID- 22093609 TI - Kinetic approach of aflatoxin B1-acetylcholinesterase interaction: a tool for developing surface plasmon resonance biosensors. AB - This work presents a kinetic approach of the interaction between acetylcholinesterase (AChE) from electric eel and aflatoxin B1 (AFB1) or its protein conjugate (e.g., AFB1-HRP [horseradish peroxidase]) in order to develop a simple and sensitive detection method of these compounds. The dissociation constant K(d) of the AChE/AFB1-HRP interaction (0.4 MUM) obtained with the surface plasmon resonance (SPR) technique is very close to the inhibition constant reported in amperometric assay (K(i)=0.35 MUM), proving that the conjugation of AFB1 to a carrier protein does not significantly influence the affinity of AFB1 for AChE. Thus, the AChE/AFB1-HRP couple can be used as mimic system for the binding of AChE to other AFB1-protein adducts and further used for developing biosensors for AFB1 bound to plasma proteins. The immobilization protocol was designed to minimize the nonspecific adsorption on the self assembled monolayer (SAM) functionalized surface of the SPR chip without an additional hydrophilic linker, whereas the interaction protocol was designed to mark out the possible occurrence of mass transport limitation (MTL) effects. The detection limits (LODs) were 0.008 MUM for AFB1-HRP (2.5 ng ml-1 AFB1) and 0.94 ng ml-1 for AFB1 itself, which is lower than recently reported values in spectrophotometric and amperometric assays. PMID- 22093610 TI - Glycolate and 2-phosphoglycolate content of tissues measured by ion chromatography coupled to mass spectrometry. AB - Glycolate and 2-phosphoglycolate (PG) are 2-carbon monocarboxylic acids with ill defined metabolic roles. Their concentrations have not yet been described in tissues apart from body fluids and erythrocytes. We describe the use of ion chromatography coupled with mass spectrometry (IC-MS) to quantify levels of glycolate and PG in tissue. Sample preparation and analysis can be performed within an hour. Low concentrations of glycolate (12-48 nmol/g) and PG (4-17 nmol/g) were detected in all tissues. The availability of this IC-MS assay will facilitate investigations of the origin, function, and metabolism of glycolate and PG in tissues. PMID- 22093611 TI - Chromophore maturation and fluorescence fluctuation spectroscopy of fluorescent proteins in a cell-free expression system. AB - Cell-free synthesis, a method for the rapid expression of proteins, is increasingly used to study interactions of complex biological systems. GFP and its variants have become indispensable for fluorescence studies in live cells and are equally attractive as reporters for cell-free systems. This work investigates the use of fluorescence fluctuation spectroscopy (FFS) as a tool for quantitative analysis of protein interactions in cell-free expression systems. We also explore chromophore maturation of fluorescent proteins, which is of crucial importance for fluorescence studies. A droplet sample protocol was developed that ensured sufficient oxygenation for chromophore maturation and ease of manipulation for titration studies. The kinetics of chromophore maturation of EGFP, EYFP, and mCherry were analyzed as a function of temperature. A strong increase in the rate from room temperature to 37 degrees C was observed. We further demonstrate that all EGFP proteins fully mature in the cell-free solution and that brightness is a robust parameter specifying stoichiometry. Finally, FFS is applied to study the stoichiometry of the nuclear transport factor 2 in a cell-free system over a broad concentration range. We conclude that combining cell-free expression and FFS provides a powerful technique for quick, quantitative study of chromophore maturation and protein-protein interaction. PMID- 22093612 TI - Effect of antibody modifications on its biomolecular binding as determined by surface plasmon resonance. AB - A surface plasmon resonance (SPR)-based procedure was developed to determine the effect of antibody modifications on its biomolecular binding behavior. Mouse immunoglobulin G (IgG) was immobilized on a protein A-functionalized gold-coated SPR chip. Goat anti-mouse IgG and its various commercially available modifications (i.e., conjugated with atto 550, atto 647, tetramethylrhodamine isothiocyanate [TRITC], horseradish peroxidase [HRP], or biotin) were employed in exactly the same concentration for the detection of mouse IgG. The various modifications of goat anti-mouse IgG decreased its biomolecular binding to mouse IgG in the order of unmodified>HRP-labeled>atto 550-labeled>biotinylated>TRITC labeled>atto 647-labeled. PMID- 22093613 TI - Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation. AB - Various antiplatelet and anticoagulation options are available for stroke prevention in patients with atrial fibrillation (AF). Currently, it is unclear whether these agents differ in their propensity to cause major gastrointestinal bleeding (MGIB). To our knowledge, no systematic evaluation of MGIB rates from randomised controlled trials (RCTs) of pharmacological stroke prevention in patients with AF has been conducted. Two independent investigators conducted systematic literature searches in MEDLINE and CENTRAL from the earliest possible date through November 2010. To be included, RCTs had to evaluate an adult population with AF or flutter and report data on the incidence of MGIB. Peto's odds ratios (ORs) with associated 95% confidence intervals (CIs) were calculated for all possible pair-wise comparisons of pharmacological stroke prevention alternatives. A total of 16 unique trials (n = 42,983) met inclusion criteria. The reported incidence of MGIB in placebo or control arms of identified trials was as high as 1.5%. Upon pair-wise meta-analysis of different pharmacological strategies, adjusted-dose vitamin K antagonists (VKAs) were found to be associated with a higher odds of MGIB compared with placebo/control (OR 3.21, 95% CI 1.32-7.82) and aspirin (or triflusal or indobufen) (OR 1.92, 95% CI 1.08 3.41). The addition of aspirin (or triflusal) to an adjusted-dose VKA resulted in greater odds of MGIB compared with aspirin alone (OR 4.72, 95% CI 1.35-16.49) and adjusted-dose VKA alone (OR 2.66, 95% CI 1.05-6.74). While aspirin increased the odds of MBIG by 3.23-fold compared with placebo/control, this finding did not reach statistical significance. The combination of aspirin and clopidogrel increased patients' odds of MGIB compared with aspirin alone (OR 1.93, 95% CI 1.46-2.56). Dabigatran was associated with a 30% increased odds of MGIB compared with adjusted-dose VKA (OR 1.30, 95% CI 1.06-1.59); however, ximelagatran was not. Low-intensity VKA therapy, alone or in combination with aspirin, was not associated with increased odds of MGIB compared with any (active-) comparator. The MGIB is a concern for patients with AF receiving pharmacological stroke prevention. Current RCT data suggest that dabigatran and adjusted-dose VKA therapy are associated with the highest odds of MGIB. Aspirin was not found to increase patients' odds of MGIB; however, this finding may be the result of type 2 error. Dual therapy resulting from the addition of an antiplatelet agent was typically associated with further increased odds of MGIB compared with monotherapy. PMID- 22093614 TI - Effect of hesperetin on tyrosinase: inhibition kinetics integrated computational simulation study. AB - Tyrosinase inhibitors have potential applications in medicine, cosmetics and agriculture to prevent hyperpigmentation or browning effects. Some of the flavonoids mostly found in herbal plants and fruits are revealed as tyrosinase inhibitors. We studied the inhibitory effects of one such flavonoid, hesperetin, on mushroom tyrosinase using inhibition kinetics and computational simulation. Hesperetin reversibly inhibited tyrosinase in a competitive manner with K(i)=4.03+/-0.26 mM. Measurements of ANS-binding fluorescence showed that hesperetin induced the hydrophobic disruption of tyrosinase. For further insight, we used the docking algorithms to simulate binding between tyrosinase and hesperetin. Simulation was successful (binding energies for Dock6.3: -34.41 kcal/mol and for AutoDock4.2: -5.67 kcal/mol) and showed that a copper ion coordinating with 3 histidine residues (HIS61, HIS85, and HIS259) within the active site pocket was chelated via hesperetin binding. Our study provides insight into the inhibition of tyrosinase in response to flavonoids. A combination of inhibition kinetics and computational prediction may facilitate the identification of potential natural tyrosinase inhibitors such as flavonoids and the prediction of their inhibitory mechanisms. PMID- 22093615 TI - NIH-3T3 fibroblasts cultured with plasma from colorectal cancer patients generate poorly differentiated carcinomas in mice. AB - The ability of cells to undergo cellular transitions, in particular, to switch between epithelial and mesenchymal states, might be highly advantageous during the progression of carcinoma. Using histological and immunohistochemical techniques, we here show that the injection into mice of spontaneously transformed NIH-3T3 cells generated fusocellular sarcomas, whereas NIH-3T3 cells that had been transformed by culturing with plasma from colorectal cancer patients gave rise to tumors that phenotypically resembled the carcinomas of the original cancer patients. Thus, plasma from cancer patients is able to transform NIH-3T3 fibroblasts into malignant epithelial-like cells, suggesting that such cells might undergo mesenchymal to epithelial transition during plasma-induced transformation. PMID- 22093616 TI - A novel gain-of-function mutation of TGF-beta receptor II promotes cancer progression via delayed receptor internalization in oral squamous cell carcinoma. AB - We present a novel gain-of-function mutation of TGF-beta receptor II (TbetaRII) found in human oral squamous cell carcinoma (OSCC). Expression of E221V/N238I mutant TbetaRII enhanced TGF-beta signaling. Mutation of TbetaRII conferred cells higher migratory and invasive capabilities and MMP-2 activity. In mouse tumor model, mutant tumors exhibited poor differentiation and E-cadherin relocalization to the cytosol. Lipid-raft-dependent endocytosis of TbetaRII was attenuated in mutant TbetaRII, suggesting that enhancement of TGF-beta signaling by this mutation is due to delayed TbetaRII internalization. Taken together, our results show a novel gain-of-function TbetaRII mutation, which enhances TGF-beta signaling leading to more invasive phenotypic changes in human OSCC. PMID- 22093617 TI - Requirement of p38 MAPK for a cell-death pathway triggered by vorinostat in MDA MB-231 human breast cancer cells. AB - Vorinostat is a histone deacetylase inhibitor that effectively suppresses cancer cell proliferation by inducing cell-cycle arrest and/or apoptosis. We now show the involvement of p38 mitogen-activated protein kinase (MAPK) in the regulation of vorinostat-induced apoptosis in MDA-MB-231 human breast cancer cells. Vorinostat induced the hyperacetylation of histone H3, which correlated to apoptosis induction. Vorinostat-induced apoptosis occurred in parallel with the phosphorylation of p38 MAPK and the dephosphorylation of extracellular signal regulated kinases 1 and 2 (ERK1/2). Knockdown of p38 MAPK prominently abrogated apoptosis induction and was accompanied by decreased caspase-3 cleavage. These findings support the notion that the activation of the p38 MAPK pathway followed by caspase-3 cleavage is responsible for vorinostat-induced apoptosis in MDA-MB 231 cells. PMID- 22093618 TI - Re-expression of miR-199a suppresses renal cancer cell proliferation and survival by targeting GSK-3beta. AB - Recently, we have identified GSK-3 as a new therapeutic target in renal cell cancer (RCC). miR-199a could potentially downregulate GSK-3beta expression. Here, we found a decreased miR-199a expression in 59% (32 of 54) of RCCs and it was correlated with higher tumor stage (p < 0.05) and nuclear overexpression of GSK 3beta (p < 0.05). We show that re-expression of miR-199a downregulates GSK-3beta and suppresses cancer cell growth. Our results demonstrate low miR-199a expression as a feature of advanced RCCs, identify miR-199a as a negative regulator of GSK-3beta, and suggest re-expression of pre-miR-199a as a new potential treatment of RCC. PMID- 22093619 TI - Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis. AB - BACKGROUND: Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clinical relevance of these epitopes in MS. METHODS: Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to 3 different MOG isoforms, and quantitative titers correlated with clinical characteristics. mAbs defined unique immunodominant epitopes distinct to each of the isoforms. RESULTS: In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2% of samples high-titer anti-MOG antibodies were identified. In contrast to anti-MOG reactivity observed in a mouse model of MS, in patients with MS these never reacted with ubiquitously exposed epitopes. Moreover, in patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r = 0.574; p = 0.025). CONCLUSIONS: Thus high-titer reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS. Our study provides valuable information about requirements of anti-MOG reactivity for being regarded as a prognostic biomarker in a subtype of MS. PMID- 22093620 TI - Scedosporium apiospermum atrial mycetomas after lung transplantation for cystic fibrosis. AB - A 37-year-old patient with cystic fibrosis underwent double lung transplantation. She developed disseminated Scedosporium apiospermum infection 2 months after surgery. Along with multiple brain abscesses, lung infection, and chorioretinitis, a cardiac echo revealed 2 large intra-atrial mycetomas floating close to the right upper pulmonary vein orifice. The mycetomas were removed through a trans-atrial approach under cardiopulmonary by pass; histology and cultures confirmed the diagnosis. Despite intensive treatment, the patient succumbed from massive brain hemorrhage on the 10th postoperative day. PMID- 22093621 TI - [Epidemiological trend and control strategy of colorectal cancer in China]. PMID- 22093623 TI - [Effects of Cdc42 overexpression on the estrogen-enhanced multidrug resistance in breast cancer cells]. AB - OBJECTIVE: To investigate the changes of Cdc42 expression under estrogen stimulation, and to explore the signaling pathway of intracellular material transportation caused by estrogen. METHODS: MTT was used to test the drug sensitivity of cells. Real-time PCR was used to evaluate the expression of Cdc42 mRNA. The amount of ADM accumulated in MCF-7 cells was detected by flow cytometry. The protein levels of active-Cdc42 and Total-Cdc42 were measured by Western blot. RESULTS: IC(50) of ADM in MCF-7 cells was increased from (0.098 +/- 0.011) ug/ml to (0.134 +/- 0.130) ug/ml (P < 0.05) after estrogen stimulation. The amount of ADM accumulated in MCF-7 cells was reduced from 7.253 +/- 0.310 to 3.233 +/- 0.313 (P < 0.05). All of Cdc42 mRNA, active-Cdc42 protein and total Cdc42 protein were increased (P < 0.05). After the treatment with siRNA, the IC(50) of ADM in siRNA group was decreased to (0.057 +/- 0.017) ug/ml (P < 0.05) compared with that in the control group. The amount of accumulated ADM was significantly increased in the siRNA group, and all the expression levels of Cdc42 mRNA, active-Cdc42 protein and total-Cdc42 protein were decreased in the siRNA group (P < 0.05). CONCLUSIONS: Estrogen enhances the drug resistance in breast cancer cells. The mechanism of this effect may be via the enhancing Cdc42 expression and decreasing the accumulation of chemotherapeutic drugs in the cancer cells. PMID- 22093622 TI - [Cisplatin enhances TRAIL-induced apoptosis in gastric cancer cells through clustering death receptor 4 into lipid rafts]. AB - OBJECTIVE: Gastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To sensitize gastric cancer cells to TRAIL, we treated gastric cancer MGC803 cells with TRAIL and cisplatin. METHODS: Cell proliferation was measured using MTT assay. Cell apoptosis was determined by flow cytometry. Expression of proteins was analyzed by Western blot. The distribution of lipid rafts and death receptors was analyzed by immunofluorescence microscopy. MGC803 cells were pretreated with 50 mg/L nystatin for 1 h, and followed by the treatment of cisplatin and TRAIL. RESULTS: 100 ug/L TRAIL resulted in (8.51 +/- 3.45)% inhibition of cell proliferation and caused (3.26 +/- 0.89)% cell apoptosis in MGC803 cells. Compared with the treatment with cisplatin alone, treatment with TRAIL (100 ug/L) and cisplatin (8.49 mg/L, IC(50) dose of 24 h) led to a dramatic increase in both inhibition of cell proliferation [(52.58 +/- 4.57)% vs. (76.43 +/- 5.35)%, P < 0.05] and cell apoptosis [(23.10 +/- 3.41)% vs. (42.56 +/- 4.11)%, P < 0.05]. Moreover, cleavage of caspase-8 and caspase-3 was detected. TRAIL (100 ug/L) did not induce obvious lipid rafts aggregation and death receptor 4 (DR4) clustering, while cisplatin (8.49 mg/L) significantly promoted the localization of DR4 in aggregated lipid rafts. Pretreatment with 50 mg/L nystatin, a cholesterol-sequestering agent, triggered (3.66 +/- 0.52)% cell apoptosis after 24 h. Pretreatment with nystatin for 1 h before the addition of 8.49 mg/L cisplatin for 24 h caused a decreased tendency to cell apoptosis [(25.74 +/- 3.28)% vs. (22.76 +/- 2.97)%]. While, pretreatment with nystatin before the addition of cisplatin and TRAIL, the proportion of apoptotic cells decreased from (43.16 +/- 4.26)% to (31.52 +/- 3.99)% (P < 0.05). CONCLUSION: Cisplatin enhances TRAIL-induced apoptosis in gastric cancer MGC803 cells through clustering death receptors into lipid rafts. PMID- 22093624 TI - [Role of dysregulation of Bim in resistance of melanoma cells to endoplasmic reticulum stress-induced apoptosis]. AB - OBJECTIVE: To establish a model of ER stress-induced apoptosis with tunicamycin and to examine whether Bim is dysregulated and its potential role in resistance of melanoma cells to apoptosis under endoplasmic reticulum (ER) stress. METHODS: A model of ER stress-induced apoptosis was established with tunicamycin. Apoptotic cells were quantitated using the annexin V/propidium iodide method by flow cytometry. Hoechst staining was also used to confirm the apoptotic cell death. Western blotting was used to measure the activation of caspase-3 and -9, and the expression of Bim, GRP78, CHOP, and Foxo1 at the protein level. The expression of Bim, CHOP and Foxo1 at the mRNA level was quantitated by qPCR. The siRNA technique was used to inhibit the expression of Bim. RESULTS: Treatment of the melanoma cells with tunicamycin did not induce significant apoptosis and activation of caspase cascade, whereas it caused marked activation of caspase-3 and -9, and apoptosis in HEK293 cells which were used as a control. With exposure to tunicamycin (3 umol/L) for 12, 24, 36 hours the Bim protein levels were not increased in Mel-RM and MM200 cells. Its mRNA levels were 0.37 +/- 0.05, 0.13 +/- 0.02 and 0.02 +/- 0.01 in Mel-RM cells, while 0.41 +/- 0.06, 0.16 +/- 0.04 and 0.21 +/- 0.03 in MM200 cells, respectively. The expression of Bim mRNA was significantly reduced compared with that in the control groups of the two cell lines (P < 0.01). siRNA knockdown of Bim protected HEK293 cells against activation of caspase-3. The cell apoptosis of Bim siRNA group was (5.69 +/- 0.38)%, significantly lower than that of the siRNA control group (40.32 +/- 1.64)% and blank control group (35.46 +/- 2.01)% (P < 0.01). In the melanoma cells after exposure to tunicamycin (3 umol/L) for 6, 12, 24, and 36 hours the transcription factor CHOP at mRNA level were significantly increased and the expressions at protein level were also up-regulated. The expressions of another transcription factor Foxo1 at mRNA level significantly decreased and the expressions at protein level were down-regulated, too. CONCLUSIONS: The lack of Bim up-regulation contributes to the resistance of melanoma cells to ER stress induced apoptosis and may be a mechanism by which melanoma cells adapt to ER stress conditions. Transcription factors CHOP and Foxo1 may be responsible for the dysregulation of Bim in melanoma cells upon ER stress. PMID- 22093625 TI - [Effect of tagalsin on p53 and Bcl-2 expression in hepatoma H(22) tumor-bearing mice]. AB - OBJECTIVE: To explore the effect and mechanism of tagalsin on hepatoma cells. METHODS: The animal models were established by transplanting H(22) mouse hepatoma cells to mouse liver, and ten days later the mice were randomly divided into five groups: blank group, carmofur positive group and tagalsin groups, including low dose, middle-dose and high-dose groups. Then medicine or oil was given to the mice by gastric gavage in consecutive 5 days with a 2-days interval as a course of treatment, two courses in all. All mice were killed at 24 hours after medication, and the survival period, ascites conditions, aggressive conditions intra- or extra-liver, weight changes, tumor volume and spleen index of the tumor bearing mice were observed. Pathological changes of the tumors were examined. Apoptotic factors p53 and Bcl-2 protien and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT PCR). RESULTS: tagalsin inhibited the hepatoma growth effectively without influencing spleen index to some extent. The tumor inhibition rate of tagalsin low, middle and high dose groups were 17.9%, 63.1% and 71.8%, respectively. Immunohistochemical results showed that the p53 and Bcl-2 protein positive cell counts of the positive control and experimental groups were significantly lower than those of the blank group (P < 0.01). RT-PCR results showed that the p53 mRNA expression was significantly enhanced and Bcl-2 mRNA expression was decreased in the positive control groups and tagalsin treatment groups, especially in the high dose group, compared with those of the blank group (P < 0.05). CONCLUSIONS: tagalsin can inhibit the growth of mouse hepatoma cells significantly. The mechanism of its anti-tumor effect may work via up-regulating the wild type p53 gene expression and down-regulating Bcl-2 gene expression and thus regulating tumor cell apoptosis. PMID- 22093626 TI - [Comparison of the biodistribution of four contrast agents in nude mice bearing NCI-H358 human lung cancer and evaluation of their value in diagnostic imaging]. AB - OBJECTIVE: To compare the uptake of four contrast agents: (99)Tc(m)-RGD-4CK, (99)Tc(m)-N(NOET)(2), (99)Tc(m)-MIBI and (18)F-FDG in Bal B/c nude mice bearing human non-small cell lung cancer NCI-H358 and evaluate their diagnostic value in low-metabolic lung cancer. METHODS: Human bronchioloalveolar carcinoma NCI-H358 cells were subcutaneously inoculated in Bal B/c nude mice to establish mouse models bearing human lung cancer. Twenty tumor-bearing nude mice were given injection of the four contrast agent, respectively, 5 mice in each group. SPECT imaging and biodistribution of the 4 tracers in the tumor-bearing nude mice were performed. The ratios of tumor to non-tumor (T/NT) of the tracers were compared. RESULTS: The results from semi-quantification of the planar image and assessment of biodistribution showed that tumor to contralateral muscle activity ratios (T/NT) of the four tracers had statistically significant difference between each two of the four tracer groups of tumor-bearing mice (P < 0.001), with a highest value of T/NT ratio in the (99)Tc(m)-RGD-4CK group. CONCLUSIONS: NCI-H358 tumors show a higher uptake of (99)Tc(m)-RGD-4CK than (18)F-FDG. It suggests that when diagnosing a well-differentiated lung cancer such as bronchioloalveolar carcinoma, the contrast agent (99)Tc(m)-RGD-4CK may be more sensitive than (18)F FDG, and it may become a promising contrast agent in tumor imaging diagnosis. PMID- 22093627 TI - [EGFR gene copy number, ERCC1 and BRCA1 protein expression and their relationship in non-small cell lung cancer]. AB - OBJECTIVE: To evaluate the expression of epidermal growth factor receptor (EGFR) gene copy number and the expression of ERCC1 and BRCA1 proteins in patients with non-small-cell lung cancer (NSCLC) and the correlation between them. METHODS: The status of EGFR gene copy number was determined by in situ hybridization (FISH), and the expression of ERCC1 and BRCC1 proteins was examined by immunohistochemistry (IHC). The relationship of EGFR gene copy number with the expression of ERCC1 and BRCA1 and the clinical pathologic features were analyzed. RESULTS: FISH-positive EGFR expression was identified in 40 of 166 samples (24.1%). More FISH-positive EGFR in the female than male patients (31.9% vs. 18.6%, P = 0.048), and non-smoker than smoker (32.8% vs. 16.7%, P = 0.045). FISH positive EGFR was not associated with age, pathological type, clinical stage and metestasis status (P > 0.05). The expression of ERCC1 protein was identified in 60 of 132 samples (45.5%). The expression of ERCC1 protein varied significantly in tumors of different pathological types (P = 0.046), but not associated with age, gender, clinical stage, metestatic status and smoking status (P > 0.05). The expression of BRCA1 protein was identified in 46 of 131 samples (35.1%). The expression of BRCA1 was not associated with age gender, pathological type, clinical stage, metestatic ststus and smoking status (P > 0.05). There was a moderate correlation between the expressions of ERCC1 and BRCA1 (r = 0.449, P < 0.001), but EGFR gene copy number was not correlated with the expression of ERCC1 or BRCA1 protein. CONCLUSIONS: FISH-positive EGFR expression is associated with gender and smoking status, but not correlated with the expression of ERCC1 and BRCA1 proteins. There is a moderate correlation between the expressions of ERCC1 and BRCA1. PMID- 22093628 TI - [Expression of indoleamine 2, 3-dioxygenase and its correlation with prognosis in breast cancer patients]. AB - OBJECTIVE: To investigate the expression of indoleamine 2, 3-dioxygenase (IDO) in breast cancer and its correlation with clinicopathologic factors and prognosis. METHODS: The expression of IDO, CD31, CD105 proteins in 40 specimens of breast cancer were assessed by immunohistochemistry. RESULTS: The overexpression rate of IDO in breast cancer was 67.5% (27/40), and expression of IDO was closely associated with clinical stage and lymph nodes metastasis. The disease-free survival rate in patients with IDO overexpression was not significantly lower than that in patients with negative or low expression of IDO (P > 0.05). Moreover, the expression of IDO was positively correlated with CD105-labeled microvessel density (r = 0.659, P < 0.05). CONCLUSIONS: Expression of IDO is associated with clinical stage and lymph nodes metastasis, and microvessel densitty. IDO expression may promote the growth and metastasis of breast cancer, probably via the increased agiogenesis. A larger sample study is needed to verify whether the prognosis of beast cancer is significantly correlated with IDO expression. PMID- 22093629 TI - [A randomized controlled trial of two chemotherapy regimens (paclitaxel liposome combined with platinum and paclitaxel combined with platinum) in concurrent chemoradiotherapy for cervical carcinoma]. AB - OBJECTIVE: To compare the efficacy, side effects and influence of two chemotherapy regimens, paclitaxel liposome combined with platinum and paclitaxel combined with platinum, on the survival rate in patients with cervical carcinoma receiving concurrent chemoradiotherapy. METHODS: One hundred and sixty two cases with primary cervical carcinoma diagnosed and treated in the Jiangxi Maternal and Children Hospital between January 2008 and November 2009 were enrolled in this randomized controlled trial. Seventy one cases were included in the paclitaxel group and 91 in the paclitaxel liposome group. The chemotherapy doses were as followings: paclitaxel liposome and paclitaxel 135 mg/m(2); cisplatin 80 mg/m(2) or carboplatin AUC 4 - 6, repeated every 21 days for two or three times. Radical radiotherapy was given to both groups at the same time. The efficacy was evaluated by the tumor regression and the patients were followed-up for six months. RESULTS: The overall response rates of paclitaxel group and paclitaxel liposome group were 90.1% and 89.0%, respectively (P > 0.05). The 1-year cumulative survival rate was 91.4% for the paclitaxel group and 89.2% for the paclitaxel liposom group (P > 0.05). The incidence rate of adverse effects such as rash, gastrointestinal toxicity, bone marrow suppression and muscle/joint pain in the paclitaxel liposome group was significantly lower than that in the paclitaxel group (P < 0.05), while there was no significant difference regarding the hair loss, liver damage, and peripheral neuritis (P > 0.05). CONCLUSIONS: Paclitaxel liposome plus platinum is a safe and effective therapeutic regimen for stage IIa-IV cervical carcinoma. However, the long-term efficacy of this regimen should be further observed. PMID- 22093630 TI - [Effects of anastrozole on lipid metabolism in Chinese postmenopausal women with breast cancer]. AB - OBJECTIVE: The aim of this study was to evaluate the effect of anastrozole, a new generation aromatase inhibitor, on the lipid metabolism in postmenopausal Chinese women with early breast cancer, and observe the adverse reactions as well. METHODS: Postmenopausal women with early breast cancer patients took anastrozole 1 mg per day. The lipid profiles of total cholesterol, triglyceride, low density lipoprotein, and high density lipoprotein were assessed before taking the drug, 3 months, 6 months after taking medication, and later once a year, until the end of medication or follow-up. Patients taking lipid-lowering drugs were excluded. The adverse reactions during the process of taking medication was followed-up by telephone. RESULTS: Two hundred and eighty-five postmenopausal breast cancer patients took part in the trial from Jan. 2003 to Jun. 2009. All patients had completed primary surgery and demonstrated a postmenopausal status. ER or PR positivity was confirmed by histopathology. Taking the medication from a minimum of one year to a maximum of 5 years, with a median time of 3.61 years. During the medication time, anastrozole significantly increased the levels of low density lipoprotein-cholesterol after 6 months of treatment, continuing to 5 years, from (3.08 +/- 0.90) mmol/L to (3.59 +/- 0.59) mmol/L, with a maximal increase of 18.2% higher than that before medication. Anastrozole significantly increased the levels of total cholesterol and high density lipoprotein-cholesterol after 1 years of treatment. Anastrozole significantly reduced the levels of triglycerides after 1 years of treatment. Anastrozole showed no significant effect on serum lipids in the patients with pre-existing hyperlipidemia. A more significant effect on blood lipids was observed in patients aged >= 60-years than that in patients less than 60 years of age. The rate of other adverse events were similar to that reported in foreign patients. CONCLUSIONS: For the postmenopausal patients with breast cancer, taking anastrozole may lead to an abnormal lipid metabolism. Anastrozole significantly increases the levels of low density lipoprotein-cholesterol, total cholesterol and high density lipoprotein cholesterol, and significantly reduces the level of triglycerides. The rate of other adverse events were similar to that reported in foreign patients. it is suggested that the blood lipid levels should be regularly assessed in patients with long-term anastrozole treatment. The rate of other adverse events similar to that reported with foreign patients, and patients tolerate this treatment well. PMID- 22093631 TI - [Dose escalation of domestic nedaplatin used in concurrent chemoradiotherapy for cervical cancer]. PMID- 22093632 TI - [Correlation between VEGF-C expression in peripheral blood, lymph nodes and tumor tissues in patients with non-small cell lung cancer]. PMID- 22093633 TI - [Therapeutic efficacy of three-dimensional conformal radiation therapy for patients with locally advanced non-small cell lung cancer]. AB - OBJECTIVE: To compare the treatment results of three-dimensional conformal radiotherapy (3D-CRT) and conventional radiotherapy (2D) for patients with locally advanced non-small-cell lung cancer (NSCLC). METHODS: Five hundred and twenty seven patients with stage III NSCLC treated between Jan 2000 and Dec 2006 were included in this study. Among them, 253 cases were treated with 3D-CRT, and 274 with conventional radiotherapy. In the 3D group, 159 (62.8%) patients received chemoradiotherapy, 77 with total radiotherapy dose of > 60 Gy, 49 with 50 - 60 Gy. In the 2D group, 127 (46.4%) patients received chemoradiotherapy, 48 with total radiotherapy dose of > 60 Gy, 75 with 50 - 60 Gy. RESULTS: The 1-, 3-, 5-year overall survival rates (OS) and median survival time for patients treated with 3D-CRT were 73.3%, 26.1%, 14.4% and 20.1 months, respectively, and that of patients treated with 2D radiotherapy were 61.0%, 13.8%, 8.0% and 15.6 months, respectively (P = 0.002). The 1-, 3-, 5-year cause-specific survival rates (CSS) were 79.0%, 33.3%, and 20.8% for the 3D group and 65.1%, 16.7%, 11.2%, respectively, for the 2D group (P = 0.000). The 1-, 3-, and 5-year locoregional control rates were 71.6%, 34.3% and 31.0% for patients treated with 3D radiotherapy and 57.3%, 22.1% and 19.2%, respectively, for patients treated with 2D treatment (P = 0.002). The results of multivariate analysis showed that 3D CRT, KPS, clinical tumor response and pretreatment hemoglobin level were independently associated with increased OS and CSS. No statistically significant differences were found between the radiation complications in the two groups. CONCLUSIONS: The results of our study demonstrate that 3D-conformal radiotherapy improves the survival rate in patients with stage III NSCLC compared with that of 2D radiation therapy. PMID- 22093634 TI - [Endovascular placement of iodine-125 seed strand and self-expandable stent combined with transcatheter arterial chemoembolization for hepatocellular carcinoma with tumor thrombus in the main portal vein]. AB - OBJECTIVE: To evaluate the therapeutic effect of endovascular placement of iodine 125 seed strand and stent combined with transcatheter arterial chemoembolization (TACE) to treat hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein (MPVTT). METHODS: Fifty patients with HCC complicated by MPVTT were enrolled into this study. There were 46 men and 4 women with a mean age of 53.9 years. TACE was performed after the iodine-125 seed strand and self-expandable stent placement in the obstructed segment of the main portal vein (MPV). RESULTS: Technical success rate was 100% for placement of iodine-125 seed strand and stent in the target segment of MPV. No serious procedure-related complications occurred. The mean follow-up duration was 208.5 d. The mean and median survival time was 370.1 d and 223.0 d, respectively. The 90-, 180-, 360-day cumulative survival rates were 97.5%, 59.3%, and 38.4%, respectively. The mean and median patent time of stent was 524.2 d and 407.4 d, respectively. The 90-, 180-, 360 day cumulative patency rates of stent were 94.9%, 75.2%, and 64.5%, respectively. CONCLUSION: Endovascular placement of iodine-125 seed strand and stent combined with TACE is an effective therapy for HCC with tumor thrombus in the main portal vein. PMID- 22093635 TI - [Diagnostic value of combining detection of human epididymis protein 4 and CA125 in patients with malignant ovarian carcinoma]. AB - OBJECTIVE: To investigate the clinical value of combination of human epididymis protein 4 (HE4), CA125 and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosis of ovarian carcinoma. METHODS: To detect the serum concentration of HE4 using ELISA and CA125 using ECL in patients of ovarian carcinoma group (n = 119), borderline ovarian tumor group (n = 36), benign ovarian neoplasm group (n = 96) and female healthy control group (n = 53). The ROMA based on the serum level of CA125, HE4 and a woman's menopausal status was used to calculate the predicted probability (PP) and diagnostic results of ovarian cancers. RESULTS: The receiver operating characteristic (ROC) analysis showed the cut-off value was 67.3 pmol/L (the AUC was 0.906, the sensitivity was 80.7% and specificity was 94.6%). The serum levels of HE4 and CA125 in the ovarian carcinoma group were significantly higher than that in the borderline ovarian tumor group, benign ovarian neoplasm group and female healthy control group (P < 0.01). The serum levels of CA125 and HE4 showed statistically no significant difference between the borderline ovarian tumor group and benign ovarian neoplasm group (P > 0.05). The levels of HE4 and CA125 were reduced significantly in ovarian patients after surgery therapy (P < 0.01). The sensitivity and specificity of HE4 + CA125 combination was 92.7% and 72.5%. The ROMA that can classify patients into high and low risk groups was established as 9.3% in premenopausal and 27.3% in postmenopausal women. CONCLUSIONS: HE4 is a helpful biomarker for ovarian carcinoma diagnosis. Biomarker combination of HE4 and CA125, and applying of the ROMA are helpful to improve the accuracy in diagnosis of ovarian cancers. PMID- 22093636 TI - [Predictive value of (99)Tc(m)-MIBI scintimammography in evaluation of the efficacy of neoadjuvant chemotherapy in patients with operable breast cancer]. AB - OBJECTIVE: To investigate the value of technetium-99m methoxyisobutylisonitrile ((99)Tc(m)-MIBI) imaging in predicting the efficacy of neoadjuvant chemotherapy (NCT) and prognosis in patients with operable breast cancer. METHODS: Sixty five patients with breast cancer underwent (99)Tc(m)-MIBI scintimammography before NCT, and static planar images were taken at 10 min and 180 min after scintimammography. The clearance rate was calculated in each patient, correlation between the clearance rate and efficacy of NCT, and the disease free survival rate were analyzed. RESULTS: The mean clearance rate of 65 patients was (17.4 +/- 6.8)%. The efficacy of NCT was 86.2% (CR 4 cases, PR 52 cases, SD 8 cases, and PD 1 case), and the mean clearance rate of patients with good response or poor response of chemotherapy were (15.5 +/- 5.0)% and (29.2 +/- 3.2)%, respectively. There was a significant difference between the two groups. The average disease free survival rate in the group with low clearance rate was (75.8%, P = 0.046), significantly higher than that in the group with high clearance rate (53.1%). CONCLUSION: Scintimammography of (99)Tc(m)-MIBI may be used to evaluate the efficacy and prognosis of NCT for patients with operable breast cancer. PMID- 22093637 TI - [Surgical treatment of primary tracheal tumors in 63 cases]. AB - OBJECTIVE: To summarize the experience in diagnosis and treatment of primary tracheal tumors, and to improve the life quality of patients. METHODS: Sixty three patients with primary tracheal tumors treated in the First Affiliated Hospital of China Medical University during the past 40 years were included in this study, among them, there were 42 cases of malignant tumors and 21 cases of benign tumors. The 61 patients underwent surgery including tracheal sleeve resection (22), carinal resection and reconstruction (6), semi-carinal resection and reconstruction (6), tracheal resection for tracheal tumors (17); tracheostomy (4), tracheal resection, partial resection of the thyroid (goiter) and esophagomyotomy (1), tracheal tumor resection and vertical hemilaryngectomy with reconstruction of laryngeal ventricle and trachea by sternocleidomastoid flap (2), cervical trachea and laryngeal resection (1), and carinal scrape (2). RESULTS: Fifty-five patients had an uneventful recovery. Eight patients suffered from postoperative complications, among them 3 patients died postoperatively. CONCLUSIONS: Primary tracheal tumors often present atypical symptoms, are easily misdiagnosed and with poor prognosis. The main aim of treatment remains to remove the airway obstruction. PMID- 22093638 TI - [Diagnosis and treatment of occult breast cancer in 44 cases]. AB - OBJECTIVE: To summarize the experience of diagnosis and treatment of occult breast cancer in 44 cases. METHODS: Clinicopathological data of 44 cases of occult breast cancer initially presenting axillary mass alone treated in our department during Jan 1997 to Dec 2008 were retrospectively analyzed. RESULTS: The 44 patients with occult breast cancer accounted for 0.42% of all breast cancer patients admitted to our hospital and institute in the same period. The surgery included radical mastectomy in 16 cases, modified radical mastectomy in 19 cases, axillary clearance in 1 case, and simple axillary node excision in 8 cases. Follow-up, ranging from 12-132 months, was available in 38 cases. Among 32 cases who underwent mastectomy or axillary clearance, 2 cases died of distant metastases and 3 cases were still alive with local recurrence at the time of analysis. In two out of six cases who refused further surgical treatment received mastectomy 16 months and 41 months after the primary diagnosis of occult breast cancer, respectively. Others were alive without evidence of recurrence or metastases at the time of analysis. CONCLUSIONS: Occult breast cancer should be taken into consideration in cases presenting with axillary metastasis of unknown primary origin. The treatment of occult breast cancer should include modified radical mastectomy/radical mastectomy or breast conserving surgery combined with breast irradiation. PMID- 22093639 TI - [Clinical analysis of 79 gastrointestinal tract stromal tumor cases]. PMID- 22093640 TI - [Pros and cons of total thyroidectomy]. PMID- 22093641 TI - The pathoplasticity of dysphoric episodes: differential impact of stressful life events on the pattern of depressive symptom inter-correlations. AB - BACKGROUND: Previous research has shown that stressful life events (SLEs) influence the pattern of individual depressive symptoms. However, we do not know how these differences arise. Two theories about the nature of psychiatric disorders have different predictions about the source of these differences: (1) SLEs influence depressive symptoms and correlations between them indirectly, via an underlying acute liability to develop a dysphoric episode (DE; common cause hypothesis); and (2) SLEs influence depressive symptoms and correlations between them directly (network hypothesis). The present study investigates the predictions of these two theories. METHOD: We divided a population-based sample of 2096 Caucasian twins (49.9% female) who reported at least two aggregated depressive symptoms in the last year into four groups, based on the SLE they reported causing their symptoms. For these groups, we calculated tetrachoric correlations between the 14 disaggregated depressive symptoms and, subsequently, tested whether the resulting correlation patterns were significantly different and if those differences could be explained by underlying differences in a single acute liability to develop a DE. RESULTS: The four SLE groups had markedly different correlation patterns between the depressive symptoms. These differences were significant and could not be explained by underlying differences in the acute liability to develop a DE. CONCLUSIONS: Our results are not compatible with the common cause perspective but are consistent with the predictions of the network hypothesis. We elaborate on the implications of a conceptual shift to the network perspective for our diagnostic and philosophical approach to the concept of what constitutes a psychiatric disorder. PMID- 22093642 TI - Effects of computerized match-to-sample training on emergent fraction-decimal relations in individuals with fragile X syndrome. AB - Individuals diagnosed with fragile X syndrome (FXS), the most common known form of inherited intellectual disability, are reported to exhibit considerable deficits in mathematical skills that are often attributed to brain-based abnormalities associated with the syndrome. We examined whether participants with FXS would display emergent fraction-decimal relations following brief, intensive match-to-sample training on baseline relations. The performance profiles on tests of symmetry and transitivity/equivalence of 11 participants with FXS, aged 10-23 years, following baseline match-to-sample training were compared to those of 11 age- and IQ-matched controls with idiopathic developmental disability. The results showed that both groups of participants showed significant improvements in the baseline (trained) relations, as expected. However, participants with FXS failed to show significant improvements in the (untrained) symmetry and transitivity/equivalence relations compared to those in the control group. A categorical analysis of the data indicated that five participants with FXS and eight controls showed at least "intermediate" emergence of symmetry relations, whereas one individual with FXS and three controls showed at least intermediate emergence of transitivity/equivalence relations. A correlation analysis of the data indicated that improvements in the symmetry relations were significantly associated with improvements in the transitivity/equivalence relations in the control group (r=.69, p=.018), but this was not the case in the FXS group (r=.34, p>.05). Participant IQ was significantly associated with improvements in the symmetry relations in individuals with FXS (r=.60, p=.049), but not in controls (r=.21, p>.05). Taken together, these results suggest that brief, computerized match-to-sample training may produce emergent mathematical relations for a subset of children with FXS and developmental disabilities. However, the ability of individuals with FXS to form transitivity/equivalence relations may be impaired relative to those with idiopathic developmental disabilities, which may be attributed to neurodevelopmental variables associated with the syndrome. PMID- 22093643 TI - Are French dyslexic children sensitive to consonant sonority in segmentation strategies? Preliminary evidence from a letter detection task. AB - This paper aims to investigate whether--and how--consonant sonority (obstruent vs. sonorant) and status (coda vs. onset) within syllable boundaries modulate the syllable-based segmentation strategies. Here, it is questioned whether French dyslexic children, who experience acoustic-phonetic (i.e., voicing) and phonological impairments, are sensitive to an optimal 'sonorant coda-obstruent onset' sonority profile as a cue for a syllable-based segmentation. To examine these questions, we used a modified version of the illusory conjunction paradigm with French dyslexic children compared with both chronological age-matched and reading level-matched controls. Our results first showed that the syllable-based segmentation is developmentally constrained in visual identification: in normally reading children, it appears to progressively increase as reading skills increase. However, surprisingly, our results also showed that dyslexic children were able to use syllable-sized units. Then, data highlighted that a syllable based segmentation in visual identification basically relies on an optimal 'sonorant coda-obstruent onset' sonority profile rather than on phonological and orthographic statistical properties in normally reading children as well as, surprisingly, in dyslexic children. Our results are discussed to support a sonority-modulated prelexical role of syllable-sized units in visual identification in French, even in dyslexic children who exhibited a developmentally delayed profile. We argue that dyslexic children have deficits in online phonetic-phonological processing rather than degraded or underspecified phonetic-phonological representations. PMID- 22093644 TI - Psychiatric literacy and the conduct disorders. AB - Past research regarding mental health literacy has indicated that public knowledge is lamentably poor. This study aimed to examine the effect of demographics, experience and personality, as predictors for understanding conduct disorders. An opportunistic sample of 125 participants with a mean age of 24.29 years completed an online questionnaire in which they were asked to describe and evaluate vignettes of 4 conduct disorders. They were asked for their view of what the diagnosis may be: "What is the main problem", confidence in their diagnosis, and how the person could be helped. The correct diagnosis was given by 42% of the participants in one case but only 8% in another. A content analysis suggested that five types of diagnosis were given: psychological/psychiatric, behavioural, parenting, socio-emotional and lifestyle. There were significant differences in what treatments were thought to be useful between the cases though psychotherapy was thought to be most useful. Limitations of this study are considered. PMID- 22093645 TI - Antipsychotic medication prescription patterns in adults with developmental disabilities who have experienced psychiatric crisis. AB - Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics taking 2 or more antipsychotics at once. Predictors of multiple antipsychotic use included gender, residence, psychiatric diagnosis and previous hospitalizations. Implications of medication prescriptions to this vulnerable population are discussed. PMID- 22093646 TI - Assisting people with disabilities to actively improve their collaborative physical activities with Nintendo Wii Balance Boards by controlling environmental stimulation. AB - The latest researches have adopted software technology to modify the Nintendo Wii Balance Board functionality and used it to enable two people with developmental disabilities to actively perform physical activities. This study extended the latest research of the Wii Balance Board application to assess whether four people (two groups) with developmental disabilities would be able to actively improve their physical activities collaboration--walking to the designated location following simple instructions, by controlling their favorite environmental stimulation through using three Nintendo Wii Balance Boards. We employed an A-B-A-B design, with A represented the baseline and B represented intervention phases. Data showed that both groups of participants significantly increased their collaborative target response (collaboratively performing designated physical activities) by activating the control system to produce their preferred environmental stimulation during the intervention phases. Practical and developmental implications of the findings are discussed. PMID- 22093647 TI - Gaze behaviour during interception in children with spastic unilateral cerebral palsy. AB - Anticipatory gaze behaviour during interceptive movements was investigated in children with Spastic Unilateral Cerebral Palsy (SUCP), and related to the side of the intracerebral lesion. Five children with lesions of the right hemisphere (RHL) and five children with lesions of the left hemisphere (LHL) had to walk towards and intercept a ball that moved perpendicular to the walking path. Interception accuracy and gaze patterns were measured in a no-occlusion and occlusion condition, in which the ball was occluded from view for half of its trajectory. There was a clear support for a relationship between gaze behaviour and success in interception performance, with some evidence for the presence of anticipatory gaze behaviour. There were also differences in gaze behaviour between children with RHL and children with LHL that might be related to planning, but these did not affect interception accuracy. It is concluded that gaze behaviour during interceptive movements is anticipatory, and at least partly dependent on the lesional side. PMID- 22093648 TI - Self-perception of children and adolescents with Mobius sequence. AB - Mobius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. Some studies suggest that psychosocial and psychiatric problems might be increased among affected persons. So far, there have been no studies on the self-perception of children and adolescents with the sequence. Seventeen participants with Mobius sequence (9 male, 8 female) aged 9-15 (mean: 11.59) years were studied. None of the probands was mentally retarded or had a diagnosis of autism spectrum disorder. Participants filled out well standardized German questionnaires on depression (Depressionsinventar fur Kinder und Jugendliche [DIKJ]), anxiety (Angstfragebogen fur Schuler [AFS]) and personality aspects (Personlichkeitsfragebogen fur Kinder von 9-14 Jahren [PFK 9-14]). Additionally, their primary caregivers were asked to complete a special questionnaire to compile the probands' personal, somatic and psychosocial history as well as the German version of the Strengths and Difficulties Questionnaire, Parent Form [SDQ-Deu]. According to the participants' self-perception only one girl scored clinical (t-score >= 63) for manifest anxiety [AFS] and depression [DIKJ] (5.9% vs. 10% in the general population). Moreover, the whole sample reported significantly lower test anxiety (p=0.000) and manifest anxiety (p=0.005) [AFS] whereas general anxiety as a personality aspect [PFK 9-14] did not differ from the normative sample. Compared to normative data, subjects expressed significantly less depression (p=0.023) and impulsivity (p=0.042). One out of 17 subjects was rated abnormal for total problems on the SDQ-Deu (5.9% vs. 10% of the normative sample), five participants scored abnormal for social problems (29.4%) and three for emotional problems (17.6%). Social problems correlated significantly with the probands' age (rho=0.707; p=0.002). As Mobius patients have severe difficulties with facial expression of feelings, and others might therefore falsely recognize them as serious or even depressed, the subjects' self-perception is crucial for assessment and diagnosis, especially if it differs considerably from that of the primary caregivers. PMID- 22093650 TI - A process evaluation of the Friendships and Dating Program for adults with developmental disabilities: measuring the fidelity of program delivery. AB - Adults with intellectual and developmental disabilities are frequently abused in dating and partnered relationships. The Friendships and Dating Program (FDP) was developed to prevent violence in dating and partnered relationships and to teach social skills needed to develop healthy, meaningful relationships among this population. A pilot study indicated the FDP resulted in a statistically significant increase in social network size and a significant decrease in instances of interpersonal violence. This study focused on utilizing a Process Evaluation Model (PEM) to document the level of treatment fidelity in the delivery of the 20 session FDP for adults with intellectual and developmental disabilities delivered by community agency personnel. The PEM also documented the amount of content delivered to the participants during each session. Results indicated that direct service personnel delivered the program with a high level of fidelity. Additionally, participants engaged at high rates over the course of the 10-week program. Further, the results indicated the FDP topics and methods of delivery were appropriate for adults with intellectual and developmental disabilities. Programs should use a Process Evaluation Model (PEM) and methods as a routine quality control mechanism to assess provision of salient participant procedures. PMID- 22093649 TI - On the difficulty of relational concepts among participants with Down syndrome. AB - The aim of the study was to compare the difficulty of relational concepts among participants with and without intellectual disability. The French versions of the Boehm Tests of Basic Concepts Third Edition (Preschool and Kindergarten to 2nd grade) were administered to three groups of 47 participants individually matched on their total raw score on the tests. The first group comprised participants with intellectual disability of undifferentiated etiology, the second, participants with Down syndrome and the third, typical children. Item analyses using the transformed item difficulties method to detect differential item functioning across groups showed that the groups' rank-orders of item difficulty were highly similar. It is concluded that, all things being equal, relational concepts are of comparable difficulty and follow a similar sequence of development whatever the cognitive and etiological status of participants. Methodological and theoretical implications of these findings are discussed. PMID- 22093651 TI - Training with differential outcomes enhances discriminative learning and visuospatial recognition memory in children born prematurely. AB - Previous studies have demonstrated that discriminative learning is facilitated when a particular outcome is associated with each relation to be learned. When this training procedure is applied (the differential outcome procedure; DOP), learning is faster and more accurate than when the more common non-differential outcome procedure is used. This enhancement of accuracy and acquisition has been called the differential outcome effect (DOE). Our primary purpose in the present study was to explore the DOE in children born with great prematurity performing a discriminative learning task (Experiment 1) or a delayed visuospatial recognition task (Experiment 2). In Experiment 1, participants showed a faster learning and a better performance when differential outcomes were used. In Experiment 2, a significant DOE was also observed. That is, premature children performed the visuospatial recognition task better when they received differential outcomes following their correct responses. By contrast, the overall performance of full term children was similar in both differential and non-differential conditions. These results are first to show that the DOP can enhance learning of conditional discriminations and recognition memory in children born prematurely with very low birth-weight. PMID- 22093652 TI - Taekwondo training improves sensory organization and balance control in children with developmental coordination disorder: a randomized controlled trial. AB - Children with developmental coordination disorder (DCD) have poorer postural control and are more susceptible to falls and injuries than their healthy counterparts. Sports training may improve sensory organization and balance ability in this population. This study aimed to evaluate the effects of three months of Taekwondo (TKD) training on the sensory organization and standing balance of children with DCD. It is a randomized controlled trial. Forty-four children with DCD (mean age: 7.6+/-1.3 years) and 18 typically developing children (mean age: 7.2+/-1.0 years) participated in the study. Twenty-one children with DCD were randomly selected to undergo daily TKD training for three months (1 h per day). Twenty-three children with DCD and 18 typically developing children received no training as controls. Sensory organization and standing balance were evaluated using a sensory organization test (SOT) and unilateral stance test (UST), respectively. Repeated measures MANCOVA showed a significant group by time interaction effect. Post hoc analysis demonstrated that improvements in the vestibular ratio (p=0.003) and UST sway velocity (p=0.007) were significantly greater in the DCD-TKD group than in the DCD-control group. There was no significant difference in the average vestibular ratio or UST sway velocity between the DCD-TKD and normal-control group after three months of TKD training (p>0.05). No change was found in the somatosensory ratio after TKD training (p>0.05). Significant improvements in visual ratios, vestibular ratios, SOT composite scores and UST sway velocities were also observed in the DCD-TKD group after training (p<=0.01). Three months of daily TKD training can improve sensory organization and standing balance for children with DCD. Clinicians can suggest TKD as a therapeutic leisure activity for this population. PMID- 22093653 TI - The influence of supports strategies, environmental factors, and client characteristics on quality of life-related personal outcomes. AB - The concept of quality of life (QOL) is increasingly being used as a support provision and outcomes evaluation framework in the field of intellectual disability (ID). The present study used a hierarchical multiple regression research design to determine the role that available supports strategies, environmental factors, and client characteristics play in assessed quality of life-related personal outcomes. Data were collected in Arduin Foundation in The Netherlands. Participants were 186 individuals with an intellectual disability. Results indicated that QOL-outcomes were significantly impacted by the availability of support strategies, living arrangement, status of employment and level of ID. PMID- 22093654 TI - Assessing client-caregiver relationships and the applicability of the 'student teacher relationship scale' for people with intellectual disabilities. AB - Improvements in client-caregiver relationships may lead to improvements in the quality of life of clients with intellectual disabilities (ID). For this reason, interventions aimed at influencing these relationships are important. To gain insight into the nature and intention of these relationships in the ID population, suitable measurement instruments are needed. This study examines the applicability of an existing relationship questionnaire designed for primary education, called the Student-Teacher Relationship Scale (STRS) on the basis of the following research questions: (1) What is the factor structure of the STRS? (2) Are there associations between STRS scales and other conceptually comparable instruments? (3) Is the STRS reliable? The participants in this study were 46 caregivers, who assessed 350 client-caregiver relationships. Psychometric research was conducted into the factor structure (n=350), construct validity (n=146), internal consistency (n=350) and test-retest reliability (n=177) of the STRS and the reliability of the individual scores (n=350) among a study population of people with moderate and severe ID. The three-factor model of the STRS as used in primary education (1. closeness, 2. conflict, 3. dependency) was, despite minor deviations, also found in the ID population. Research into the construct validity of the STRS showed statistically significant correlations with other scales with which similarities could be expected. The internal consistency and test-retest reliability of the STRS in the population studied were very good. The 95% confidence intervals of the means were small, and these measurements can be regarded as reliable. PMID- 22093655 TI - Technology-based programs to promote walking fluency or improve foot-ground contact during walking: two case studies of adults with multiple disabilities. AB - These two case studies assessed technology-based programs for promoting walking fluency and improving foot-ground contact during walking with a man and a woman with multiple disabilities, respectively. The man showed breaks during walking and the woman presented with toe walking. The technology used in the studies included a microprocessor with specific software, an MP3 with the recordings of preferred stimulus items, and optic sensors. Both studies were carried out according to an ABAB design. In Study I, the optic sensors were activated when the man crossed small marks distributed along the travel routes. At each sensor's activation, the man received a brief period of preferred stimulation. In Study II, the woman received preferred stimulation when the sensors at the toe and the heel of her shoes were activated in close time proximity. The man walked virtually without breaks and improved his mood (with an increase in indices of happiness) during the intervention phases of the study. The woman largely increased her percentages of steps with adequate foot-ground contact, which reached a mean of about 80 during the second intervention phase. The results were discussed in terms of rehabilitation implications and technology demands. PMID- 22093656 TI - Vocabulary development in children with hearing loss: the role of child, family, and educational variables. AB - In the present study we examined the effect of hearing status on reading vocabulary development. More specifically, we examined the change of lexical competence in children with hearing loss over grade 4-7 and the predictors of this change. Therefore, we used a multi-factor longitudinal design with multiple outcomes, measuring the reading vocabulary knowledge in children with hearing loss from grades 4 and 5, and of children without hearing loss from grade 4, for 3 years with two word tasks: a lexical decision task and a use decision task. With these tasks we measured word form recognition and (in)correct usage recognition, respectively. A GLM repeated measures procedure indicated that scores and growth rates on the two tasks were affected by hearing status. Moreover, with structural equation modeling we observed that the development of lexical competence in children with hearing loss is stable over time, and a child's lexical competence can be explained best by his or her lexical competence assessed on a previous measurement occasion. If you look back, differences in lexical competence among children with hearing loss stay unfortunately the same. Educational placement, use of sign language at home, intelligence, use of hearing devices, and onset of deafness can account for the differences among children with hearing loss. PMID- 22093657 TI - Stability and harmony of gait in children with cerebral palsy. AB - The aim of this study was to quantitatively assess the stability and harmony of gait in children with cerebral palsy. Seventeen children with spastic hemiplegia due to cerebral palsy (5.0+/-2.3 years old) who were able to walk autonomously and seventeen age-matched children with typical development (5.7+/-2.5 years old, p=0.391) performed a 10-m walking test with a wearable device fixed to their lower trunk and included a triaxial accelerometer and three gyroscopes. Three parameters related to gait stability and three related to gait harmony were computed; all of these yielded significant differences between children with cerebral palsy and those with typical development (p<0.020 for all the computed parameters). In the latter group of children, trunk accelerations were found to be negatively correlated with age (partial correlation controlled for walking speed: R(p)<-0.58, p>0.020). Conversely, in children with cerebral palsy, the upper body accelerations were proportionally correlated with their gait speed (R=0.548, p=0.023 in the antero-posterior direction) but not with their age (p>0.05). This finding can be related both to difficulties in managing the higher upper body accelerations involved in rapid walking and to compensation strategies. PMID- 22093658 TI - The assessment of the likelihood of mammography usage with relevant factors among women with disabilities. AB - Research that identifies the determinants of low mammography use among disabled people is scant. This study examines the determining factors related to the low usage of mammography among women with disabilities. To identify the barriers that prevent women with disabilities from participating in mammography screening can help authorities conceive feasibly useful strategies for avoiding worse suffering. With women aged between 50 and 69 as subjects, this study was conducted using the database of Ministry of the Interior, Taiwan, in 2008, coupled with information gathered between 2006 and 2008 on preventive health care and medical claim data from the Bureau of Health Promotion and the National Health Research Institutes, respectively. This study examined the factors determining the use of mammography with logistic regression analysis. Only 8.49% of the disabled women used mammographies. When women with disabilities were in higher income level, they were more likely to use mammography for breast cancer screening. Similar findings were found for education levels. Moreover, subjects with a more severe form of disability were less likely to use mammography with ORs of 0.84, 0.63, and 0.52. Disabled women with major organ malfunction, chronic mental illness, or mental retardation had a higher likelihood to use mammography services, whereas women with multiple disabilities had the lowest likelihood of usage. Those with experience using other preventive services showed 1.9 times to 7.54 times (95% CI: 1.82-1.98, 7.15-7.95, respectively) increased likelihood of mammography usage. In summary, mammography usage is relatively different for disabled and nondisabled populations. To mitigate the disparities, we can use community healthcare institutions or public health nurses and social workers to provide related preventive health services through community events to implement integrated cancer screening services. PMID- 22093659 TI - Examining reports of mental health in adults with Williams syndrome. AB - Prior research suggests that individuals with Williams syndrome (WS) have a disposition towards anxiety. Information regarding this is typically derived from parents and carers. The perspectives of the individuals with WS are rarely included in research of this nature. We examined the mental health of 19 adults with WS using explicit (psychiatric interview) and implicit (modified Stroop task) measures and compared informant (parents/carers) and respondent (adults with WS) reports of psychiatric symptoms. Informants and respondents both reported more symptoms of anxiety (n=7-9) than depression (n=2). Strong positive correlations were found between informant and respondent reports of symptoms of mental health problems. Compared to informants, respondents reported significantly more symptoms overall and somewhat more symptoms of anxiety. Results from the Stroop task indicated that the adults with WS were more vigilant to anxiety-related words than to depression-related words. The adults with WS provided reliable information regarding their mental health, thus providing further evidence that anxiety is part of the behavioural phenotype of the syndrome. PMID- 22093660 TI - Sleep EEG fingerprints reveal accelerated thalamocortical oscillatory dynamics in Williams syndrome. AB - Sleep EEG alterations are emerging features of several developmental disabilities, but detailed quantitative EEG data on the sleep phenotype of patients with Williams syndrome (WS, 7q11.23 microdeletion) is still lacking. Based on laboratory (Study I) and home sleep records (Study II) here we report WS related features of the patterns of antero-posterior 8-16 Hz non-rapid-eye movement (NREM) sleep EEG power distributions. Participants in Study I were 9 WS and 9 typically developing (TD) controls matched for age (14-29 years) and sex, and sleeping for two consecutive nights in the laboratory. WS participants were characterized by region-independent decreases in 10.50-12.50 Hz and central increases in 14.75-15.75 Hz EEG power. Region-independent decreases and increases in z-scores of the spectra were observed in the 10.25-12.25 Hz and 14-16 Hz ranges, respectively. Moreover, in the EEG spectra of participants with WS a lower probability for the emergence of a frontally dominant peak was observed. Parietal fast sigma peaks and the antero-posterior shifts in power distributions were of higher frequencies in WS (~1 Hz difference). A 1 year follow-up of 9 WS and 3 TD participants, as well as their inclusion into larger samples (20 WS and 20 TD, age: 6-29 years) of a two-night ambulatory home polysomnography study confirmed the WS-specific decrease in alpha/low sigma power (8-11.75 Hz) and the pattern of z-score differences (decreases: 8.50-11.25 Hz; increases: 13.5-14 Hz), including the antero-posterior shifts in power distribution (0.5 Hz) and some features of the spectral peaks. Altogether these data suggest a decrease in alpha/low sigma power, as well as a redistribution of NREM sleep 8-16 Hz EEG power toward the higher frequencies and/or a higher frequency of NREM sleep thalamocortical oscillations in WS. PMID- 22093661 TI - Movement skills of younger versus older adults with and without Down syndrome. AB - Adults with Down syndrome (DS) are often physically inactive, which may accelerate the onset of disease and aging symptoms. Eight older persons with DS (aged 54-61), and 10 younger persons with DS (aged 26-35) living in a residential care center were examined. Eighteen age- and gender-matched individuals without DS served as control groups. Sensory-motor tasks and Posture Scale Analyzer (PSA) were used to examine coordination and standing stability. The isokinetic muscle strength test was used for muscle strength investigation. The functional performance, coordination, and leg muscle strength of the older adults with DS were more impaired than both the younger DS and the control groups. The older DS group showed lower sway rate and more symmetrical weight-bearing distribution during quiet standing than both the younger DS and the control groups. Our observations may have significant implications for understanding movement dysfunction in older adults with DS. PMID- 22093662 TI - Language and communication skills in preschool children with autism spectrum disorders: contribution of cognition, severity of autism symptoms, and adaptive functioning to the variability. AB - This study examined the contribution of cognitive function, severity of autism, and adaptive functioning to the variability in language and communication skills in 129 preschool children (aged 24-63 months) with autism spectrum disorder (ASD). Participants were selected from a representative research cohort of 208 preschool children on the basis of caregiver completion of the MacArthur-Bates Communicative Development Inventories (CDI). The children were classified into three cognitive groups: (a) Normal intelligence; (b) Developmental delay; and (c) Intellectual disability. Autism symptom severity was measured by the Autistic Behavior Checklist (ABC), and adaptive functioning by the Daily Living Skills (DLS) and Socialization (Soc) subscales from the Vineland Adaptive Behavior Scales. For each of five CDI variables (Phrases understood, Words understood, Words produced, Gestures and actions, and Language use), the contribution of cognition, severity of autism symptoms, and adaptive functioning to the variability was examined. Cognition and age explained about half or more of the variance in the four verbal language CDI variables, but only about one fourth of the variance in the non-verbal communication variable Gestures and actions. Severity of autism symptoms and the two adaptive measures (DLS and Soc) each only accounted for a few percent more of the variance in the four CDI language variables; however, for Gestures and actions, an additional 11-21% of the variance was accounted for. In conclusion, for children with ASD, receptive and expressive language is mainly related to cognitive level, whereas non-verbal communication skills seem to also be related to severity of autism symptoms and adaptive functioning. PMID- 22093663 TI - Effectiveness of functional progressive resistance exercise training on walking ability in children with cerebral palsy: a randomized controlled trial. AB - The objective of the study was to evaluate the effectiveness of functional progressive resistance exercise (PRE) training on walking ability in children with cerebral palsy (CP). Fifty-one ambulant children with spastic CP (mean age 10 years 5 months, 29 boys) were randomized to an intervention (n=26) or control group (n=25, receiving usual care). The intervention consisted of 12 weeks functional PRE circuit training, for 3 times a week. Main outcome measures were walking ability and participation. Secondary outcomes were muscle strength and anaerobic muscle power. Possible adverse outcomes were spasticity and passive range of motion (ROM). Muscle strength increased significantly in the training group compared to the control group, but walking ability, participation and anaerobic muscle power did not change. Spasticity and ROM remained unchanged, except for a significant decrease in rectus femoris length in the intervention group. It is concluded that twelve weeks of functional PRE-training does not improve walking ability, despite improved muscle strength. PMID- 22093664 TI - Using simultaneous prompting to teach independent living and leisure skills to adults with severe intellectual disabilities. AB - The acquisition of independent living and leisure skills enables adults to experience an enhanced quality of life by increasing competence, self-reliance, and the development of autonomy. This study examined the effectiveness of simultaneous prompting to teach behavior chains (i.e., independent living and leisure skills) to adults with SID individually in their home environments. Participants included two adults with SID receiving services from a not-for profit agency that provides community-based services and supports to persons with disabilities. The results of this study are the first to indicate the effectiveness of simultaneous prompting to teach independent living and leisure skills to adults with SID using a one-on-one format in their home environment. Both participants learned three different skills within 12-28 sessions and maintained each skill 1, 2, and 4 weeks after mastery. PMID- 22093665 TI - Differentiating children with attention-deficit/hyperactivity disorder, conduct disorder, learning disabilities and autistic spectrum disorders by means of their motor behavior characteristics. AB - The study was designed to investigate the discriminant validity of the Motor Behavior Checklist (MBC) for distinguishing four group of children independently classified with Attention-Deficit/Hyperactivity Disorder, (ADHD; N=22), Conduct Disorder (CD; N=17), Learning Disabilities (LD; N=24) and Autistic Spectrum Disorders (ASD; N=20). Physical education teachers used the MBC for children to rate their pupils based on their motor related behaviors. A multivariate analysis revealed significant differences among the groups on different problem scales. The results indicated that the MBC for children may be effective in discriminating children with similar disruptive behaviors (e.g., ADHD, CD) and autistic disorders, based on their motor behavior characteristics, but not children with Learning Disabilities (LD), when used by physical education teachers in school settings. PMID- 22093666 TI - Determining factors for utilization of preventive health services among adults with disabilities in Taiwan. AB - Taiwan has provided free health checks for adults since 1995. However, very little previous research has explored the use of preventive health services by physically and mentally disabled adults. The present study aimed to understand this use of preventive health services and the factors that influence it. Research participants included disabled people registered in a Ministry of the Interior database in 2008 (a total of 785,746 adults who met the conditions for being physically or mentally disabled and using preventive health services). These data were merged with the Bureau of Health Promotion's 2006-2008 dataset on preventive health and the 2006-2008 health insurance database published by the National Health Research Institutes. In addition to descriptive and bivariate analysis, the study used logistic regression analysis to investigate the factors that influence the use of adult preventive health services. The results showed that 15.81% of physically and mentally disabled adults used preventive health services. The rate of use among females was significantly higher than the rate among males, and rates were higher among residents of relatively less urbanized areas. Usage rates were also universally higher among sufferers of chronic diseases. However, more serious disabilities had lower usage rates. From the logistic regression analysis, we ascertained that the factors that influenced the use of preventive health services were gender, age, level of urbanization, monthly salary, low-income household status, aboriginal status, catastrophic disease/injury status, chronic diseases, type of disability, and severity of the disability. The study's main conclusion is that although Taiwan's Department of Health has provided free preventive health services for more than 15 years, the usage rate of this care among the disabled remains low. Demographic features, health status, and type of disability are the main factors influencing the use of preventive healthcare services. PMID- 22093667 TI - Defining the active ingredients of interactive computer play interventions for children with neuromotor impairments: a scoping review. AB - Rehabilitation researchers who investigate complex interventions are challenged to describe the "active ingredients" of their interventions: the reason(s) why a treatment is expected to be effective. Interactive Computer Play (ICP) is an emerging complex intervention in rehabilitation practice and research. The purpose of this scoping review is to identify the active ingredients of ICP interventions that are designed to improve motor outcomes in children with neuromotor impairments. Eleven potential active ingredients were identified with the following foci: ICP system or game properties; intervention effects on the user; and therapist roles. However, few studies explicitly evaluate the impact of particular ingredients on outcomes. Identification of active ingredients in ICP interventions can inform trial design and clinical decision-making. Research and clinical practice will benefit from studies that utilize a framework such as motor learning theory to guide hypotheses and measurement of the active ingredients of complex interventions. PMID- 22093668 TI - College students' conceptualizations of deficits involved in mild intellectual disability. AB - Precedential rulings in recent capital murder trials may, in some cases, leave it up to a jury to determine whether or not an individual meets criteria for an intellectual disability (ID) and should be spared from the death penalty. Despite the potential for misconceptions about ID to bias decisions, few empirical studies have examined the public's conceptualizations of individuals with ID. This study sought to examine 890 college students' conceptualizations of the deficits involved in mild ID. Students were asked to respond to two online surveys about the cognitive and adaptive behavior deficits that people with mild ID may experience. While most students were correct about basic facts, such as ID is not contagious and not curable, there was no clear consensus regarding beliefs about individuals with ID getting married, having children, or engaging in other mainstream activities of adult living. Students' responses are examined in light of results of studies that identify and examine bona fide deficits and areas of successful mainstreaming among persons with ID. Implications of misconceptions are discussed. PMID- 22093669 TI - Effects of a Special Olympics Unified Sports soccer program on psycho-social attributes of youth with and without intellectual disability. AB - The purpose of the study was to investigate the effects of a Special Olympics (SO) Unified Sports (UNS) soccer program on psycho-social attributes of youth with and without intellectual disabilities (ID). Participants were 76 male youth with (n=38) and without (n=38) ID. Participants with ID were randomly allocated into a SO athletes group (n=23, mean age=14.5; SD=1.2 years) and a control group (CG) (n=15, mean age=14.5; SD=.8 years). Twenty-three randomly selected youth without ID formed the partner group (mean age=14.1; SD=.9 years) and 15 youth without ID (mean age=13.8; SD=.5 years) formed the CG. Instruments included the Friendship Activity Scale (FAS) (Siperstein, 1980), the Adjective Checklist (Siperstein, 1980), and the Children Behavior Checklist (Achenbach, 1991). The soccer training program lasted eight weeks, 1.5h per session, three times per week, in addition to school physical education (PE). The CG did not participate in any sports in addition to PE. The findings showed that the UNS program was effective in decreasing the problem behaviors of youth with ID and increasing their social competence and FAS scores. In addition, the program was found to be effective in improving the attitude of youth without disabilities toward participants with disabilities. In conclusion, the present findings demonstrate the utility of a UNS program for both youth with and without disabilities. PMID- 22093670 TI - Bimanual behaviours in children aged 8-18 months: a literature review to select toys that elicit the use of two hands. AB - Toys that provoke the use of both hands are required to develop a test of bimanual performance in children 8-18 months with unilateral cerebral palsy (Mini AHA). To choose the toys, a conceptual model based on perception-action theory and object use was used to guide a literature review. Evidence was sought for three critical relationships identified in the model which help determine bimanual performance: (1) the child-toy relationship, (2) the child-task relationship, and (3) the toy-task relationship. Evidence for both typically developing children and children with unilateral CP in this age range was sought. Thirty-five papers provided information about one or more of the relationships in typically developing children. No evidence was found for children with unilateral CP. Synthesis of the evidence from these three relationships informed toy selection for this new assessment. PMID- 22093671 TI - Baroreflex sensitivity is reduced in adolescents with probable developmental coordination disorder. AB - Developmental coordination disorder (DCD) is a neurodevelopmental condition characterized by poor motor skills leading to a significant impairment in activities of daily living. Compared to typically developing children, those with DCD are less fit and physically active, and have increased body fat. This is an important consequence as both sedentary lifestyle and obesity are risk factors for cardiovascular disease. One indicator of cardiovascular health is baroreflex sensitivity (BRS), which is a measure of short term blood pressure (BP) regulation and is partly accomplished through changes in heart rate. Diminished BRS is predictive of future cardiovascular morbidity and mortality. The purpose of this study was to compare BRS in typically developing (TD) adolescents with probable DCD (pDCD) or suspect pDCD (spDCD) adolescents (13-14 years of age). Percentile scores on the Movement Assessment Battery for Children, 2nd edition, assessed at two time points were averaged and used to classify participants into the following groups: pDCD <= 5th percentile, spDCD > 5th percentile and <=16th percentile and TD>16th percentile. Following 15 min of supine rest, 5 min of continuous beat-by-beat blood pressure (Finapres) and R-R interval were recorded (standard ECG). Spectral indices were computed using Fast Fourier Transform with transfer function analysis used to compute BRS in the low frequency region (0.04 0.15 Hz). BRS was compared between groups with an ANOVA and post hoc Bonferroni correction. BRS was reduced in the pDCD compared to the TD groups. In multivariate regression analyses predicting BRS, when pDCD and spDCD were entered as the only variables, pDCD was found to be a significant predictor of BRS (b= 6.74, p=0.016). However, when sex, VO(2) peak, and percent body fat (PBF) were entered as covariates, pDCD was no longer a predictor, while PBF approached significance (-0.32, p=0.056). Therefore, in this sample, BRS was reduced in adolescents with pDCD principally due to increased PBF. PMID- 22093672 TI - The effects of diagnostic group and gender on challenging behaviors in infants and toddlers with cerebral palsy, Down syndrome or seizures. AB - Challenging behaviors are frequently studied in individuals with various developmental disabilities, although specific conditions are rarely compared to one another. Such data would be informative to clinicians who assess and develop treatment plans for children with these disabilities. For that reason, the current study's aim was to analyze problem behavior deficits in infants and toddlers diagnosed with cerebral palsy (CP), Down syndrome (DS), and a history of seizures/seizure disorder. Seventy six children participated in this study and were administered the Baby and Infant Screen for Children with aUtIsm Traits-Part 2 (BISCUIT-Part 2). Inspection of the Tantrum/Conduct Behavior subscale of this measure revealed that children with a history of seizures/seizure disorder exhibited significantly higher scores, indicating greater impairment, than those with CP or DS. Children with DS and those diagnosed with CP did not significantly differ from one another. Additionally, there was no significant main effect by gender. The CP and DS groups also had fewer endorsements on all 18 items of the subscale as compared to the seizures group. Implications of these results are discussed. PMID- 22093673 TI - Technology-aided pictorial cues to support the performance of daily activities by persons with moderate Alzheimer's disease. AB - We developed a technology-aided intervention strategy relying on pictorial cues alone or in combination with verbal instructions and assessed these two versions of the strategy with three persons with moderate Alzheimer's disease. In Section I of the study, the strategy version with pictorial cues plus verbal instructions was compared with an existing technology-based strategy with verbal instructions. Each strategy was used with one specific activity. In Section II of the study, the strategy version with pictorial cues alone was compared with the aforementioned strategy with verbal instructions. Again, each strategy was used with one activity. Both strategy versions were effective with all three participants. The percentages of correct activity performance observed with those versions increased to above 90, and were comparable with those obtained with the existing verbal instructions strategy. A social validation assessment of the version with pictorial cues alone and the existing strategy with verbal instructions (employing university psychology students as raters) showed differences in favor of the latter strategy in terms of practicality and in favor of the former in terms of respect of participants' dignity. The implications of the findings were discussed. PMID- 22093674 TI - Awareness of legal blood alcohol concentration limits amongst respondents of a national roadside survey for alcohol and traffic behaviours in Brazil. AB - BACKGROUND: In Brazil the legal blood alcohol content (BAC) allowed for driving was changed to zero in 2008. If the BAC found is above 0.6g/L, drivers may be arrested. However, there are limited data on drivers' awareness of such limits. METHODS: Drivers from 27 major metropolitan areas (n=3397) were randomly asked to participate in roadside survey from 12 a.m. to 12 p.m. on Fridays and Saturdays. They were breathalized by highway patrol officers, and after consent interviewers collected data on drinking behaviours, knowledge about the law, and breath tests results. RESULTS: The mean age was 37.3+/-11.3 years; 94.3% were male and 26.5% had some college education. When asked about the BAC that could result in arrest, 34.5% of the subjects claimed to know it. However, only 23.5% (8.1% of the total sample) provided correct answers. Factors associated with the right answers were: male gender (p=0.04; OR=2.08; CI=1.01-4.27); higher education (p<0.0001); negative BAC or self-report of driving under the influence (DUI) (p=0.02); higher family income (p=0.01) and non-professional driving (p=0.041). Age was not statistically different between groups. After multivariate analysis, male gender (p=0.002), higher education (p<0.0001) and negative BAC or DUI (p=0.046) remained in the model. CONCLUSIONS: The knowledge that BAC levels over 0.6g/L may result in arrest is sparse amongst Brazilian drivers, notably amongst women, the less educated and those who drink and drive. Educational programmes targeted at those specific groups may be necessary in order to increase awareness about the legal BAC limit and its consequences. PMID- 22093675 TI - One stop shopping - bringing services to drug users. PMID- 22093676 TI - Clients are central to any independent and rigorous evaluation of the services they use. PMID- 22093677 TI - Association of plasma epinephrine level with insulin sensitivity in metabolically healthy but obese individuals. AB - In the present study, we explored the association of catecholamines with insulin sensitivity in "metabolically healthy but obese" (MHO) individuals, by examining the metabolic characteristics and plasma catecholamine levels in 100 obese, sedentary postmenopausal women. Subjects were classified as MHO (n=25) or at-risk (n=25) based on the upper and lower quartiles of insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp technique. The MHO group presented a significantly higher range of plasma epinephrine levels (73 +/- 21 pg/mL) than the at-risk group (39 +/- 20 pg/mL) (P<0.05), though both within the normal basal range of plasma epinephrine (56 +/- 30 pg/mL). Multivariate regression analysis showed that high-sensitivity C-reactive protein, plasma epinephrine, triglycerides and lean body mass index were independent predictors of glucose disposal. The plasma epinephrine level was positively correlated with the glucose disposal rate, insulin sensitivity and the HDL-cholesterol level, and negatively correlated with the triglycerides level (P<0.05). In conclusion, this study for the first time demonstrates a positive association between plasma epinephrine level and insulin sensitivity in MHO individuals. PMID- 22093678 TI - Information sources used by the suicidal to inform choice of method. AB - BACKGROUND: Choice of suicide method strongly influences the outcome of an attempt. Public knowledge of possible methods is an important but less frequently considered aspect of the accessibility of suicide. This qualitative study explored the sources of information shaping the near-fatal suicide attempts of 22 individuals. METHODS: Respondents were recruited from nine hospitals in England. Semi-structured interviews were conducted to gain detailed narratives of the planning of the suicide attempt. Interviews were recorded, transcribed, then subjected to thematic analysis utilising constant comparison techniques. RESULTS: Information sources discussed most frequently were television, news stories, the Internet, and previous self-harm. Others were professional resources, personal knowledge of others' attempts and information gleaned from healthcare professionals. Many respondents reported seeing media portrayals or reports of suicide, which had contributed to their awareness of suicide methods. Several provided examples of direct imitation. Some had deliberately sought information about methods when planning their attempt--mostly from the Internet. Past experience was used to identify 'best' methods and perfect implementation. LIMITATIONS: The frequency with which sources of information are 'used' by particular groups and their relative import cannot be inferred from a qualitative sample. Near-fatal cases may differ from completed suicides. CONCLUSIONS: The media is an important contributor to the cognitive availability of suicide in society and could be used for prevention through carefully crafted portrayals of suicide designed to generate negative social perceptions of popular methods. Understanding of how sources of information can influence perceptions of suicide could inform the content of clinical conversations with patients. PMID- 22093679 TI - Comparison of percutaneous nephrolithotomy and retrograde flexible nephrolithotripsy for the management of 2-4 cm stones: a matched-pair analysis. AB - Study Type--Therapy (case control). Level of Evidence 3b. What's known on the subject? and What does the study add? Recently European Association of Urology 2011 guidelines on urolithiasis recommended retrograde intrarenal surgery as the second-line therapy for the treatment of kidney stones <10 mm in diameter. This study shows that retrograde intrarenal surgery may be an alternative therapy to percutaneous nephrolithotomy, with acceptable efficacy and low morbidity for 2-4 cm stones. OBJECTIVE: * Currently, the indications for retrograde intrarenal surgery (RIRS) have been extended due to recent improvements in endoscopic technology. In this study, we compare the outcomes of percutaneous nephrolithotomy (PCNL) and RIRS in the treatment of 2-4 cm kidney stones. MATERIALS AND METHODS: * Between September 2008 and January 2011, 34 patients who had renal stones ranging from 2 to 4 cm in diameter were treated with RIRS. The outcomes of these patients were compared with patients who underwent PCNL using matched-pair analysis (1:1 scenario). * The matching parameters were the size, number and location of the stones as well as age, gender, body mass index, solitary kidney, degree of hydronephrosis, presence of previous shock wave lithotripsy and open surgery. * Data were analysed using Fisher's exact test, Student's t test and the Mann-Whitney U test. RESULTS: * Stone-free rates after one session were 73.5% and 91.2% for RIRS and PCNL respectively (P= 0.05). Stone free rate in the RIRS group improved to 88.2% after the second procedure. * Mean operation duration was 58.2 (+/-) 13.4 min in the RIRS group but 38.7 (+/-) 11.6 min in the PCNL group (P < 0.0001). Blood transfusions were required in two patients in the PCNL group. * Overall complication rates in the PCNL group were higher, but the differences were not statistically significant. Hospitalization time was significantly shorter in the RIRS group (30.0 + 37.4 vs 61.4 + 34.0 h, respectively; P < 0.001). CONCLUSION: * Satisfactory outcomes can be achieved with multi-session RIRS in the treatment of 2-4 cm renal stones. RIRS can be used as an alternative treatment to PCNL in selected cases with larger renal stones. PMID- 22093680 TI - Patch depletion, niche structuring and the evolution of co-operative foraging. AB - BACKGROUND: Many animals live in groups. One proposed reason is that grouping allows cooperative food finding. Group foraging models suggest that grouping could increase food finding rates, but that such group processes could be evolutionarily unstable. These models assume discrete food patches which are fully detectable. However, often animals may only be able to perceive local parts of larger-scale environmental patterns. We therefore use a spatial individual based model where food patches are aggregates of food items beyond the scale of individual perception. We then study the evolution of foraging and grouping behavior in environments with different resource distributions. RESULTS: Our results show that grouping can evolve to increase food intake rates. Two kinds of grouping evolve: traveling pairs and opportunistic grouping, where individuals only aggregate when feeding. Grouping evolves because it allows individuals to better sense and deplete patches. Such enhanced patch depletion is particularly apparent on fragmented and partially depleted patches, which are especially difficult for solitary foragers to deplete. Solitary foragers often leave a patch prematurely because a whole patch cannot be observed directly. In groups, individuals that are still eating allow other individuals that inadvertently leave the patch, to return and continue feeding. For this information sharing a grouping tendency is sufficient and observing whether a neighbor is eating is not necessary. Grouping therefore leads to a release from individual sensing constraints and a shift in niche specialization, allowing individuals to better exploit partially depleted patches. CONCLUSIONS: The evolved group foraging can be seen as cooperative in the sense that it leads to a mutually-beneficial synergy: together individuals can achieve more than on their own. This cooperation exists as a group-level process generated by the interaction between grouping and the environment. Thus we reveal how such a synergy can originate in evolution as a side-effect of grouping via multi-level selection. Here there is no cooperative dilemma as individuals cannot avoid producing information for their neighbors. This scenario may be a useful starting point for studying the evolution of further social and cooperative complexity. PMID- 22093681 TI - Divergence in wine characteristics produced by wild and domesticated strains of Saccharomyces cerevisiae. AB - The budding yeast Saccharomyces cerevisiae is the primary species used by wine makers to convert sugar into alcohol during wine fermentation. Saccharomyces cerevisiae is found in vineyards, but is also found in association with oak trees and other natural sources. Although wild strains of S. cerevisiae as well as other Saccharomyces species are also capable of wine fermentation, a genetically distinct group of S. cerevisiae strains is primarily used to produce wine, consistent with the idea that wine making strains have been domesticated for wine production. In this study, we demonstrate that humans can distinguish between wines produced using wine strains and wild strains of S. cerevisiae as well as its sibling species, Saccharomyces paradoxus. Wine strains produced wine with fruity and floral characteristics, whereas wild strains produced wine with earthy and sulfurous characteristics. The differences that we observe between wine and wild strains provides further evidence that wine strains have evolved phenotypes that are distinct from their wild ancestors and relevant to their use in wine production. PMID- 22093682 TI - A multiplex set of species-specific primers for rapid identification of members of the genus Saccharomyces. AB - The Saccharomyces genus (previously Saccharomyces sensu stricto) formally comprises Saccharomyces arboricola, Saccharomyces bayanus, Saccharomyces cariocanus, Saccharomyces cerevisiae, Saccharomyces kudriavzevii, Saccharomyces mikatae, Saccharomyces paradoxus and Saccharomyces pastorianus. Species-specific primer pairs that produce a single band of known and different product size have been developed for each member of the clade with the exception of S. pastorianus, which is a polyphyletic allopolyploid hybrid only found in lager breweries, and for which signature sequences could not be reliably created. Saccharomyces cariocanus is now regarded as an American variant of S. paradoxus, and accordingly a single primer pair that recognizes both species was developed. A different orthologous and essential housekeeping gene was used to detect each species, potentially avoiding competition between PCR primers and overlap between amplicons. In multiplex format, two or more different species could be identified in a single reaction; double and triple hybrids could not always be correctly identified. Forty-two unidentified yeasts from sugar cane juice fermentations were correctly identified as S. cerevisiae. A colony PCR method was developed that is rapid, robust, inexpensive and capable of automation, requires no mycological expertise on the part of the user and is thus useful for large-scale preliminary screens. PMID- 22093683 TI - Assessment of the yeast species composition of cocoa bean fermentations in different cocoa-producing regions using denaturing gradient gel electrophoresis. AB - The yeast species composition of 12 cocoa bean fermentations carried out in Brazil, Ecuador, Ivory Coast and Malaysia was investigated culture-independently. Denaturing gradient gel electrophoresis of 26S rRNA gene fragments, obtained through polymerase chain reaction with universal eukaryotic primers, was carried out with two different commercial apparatus (the DCode and CBS systems). In general, this molecular method allowed a rapid monitoring of the yeast species prevailing during fermentation. Under similar and optimal denaturing gradient gel electrophoresis conditions, the CBS system allowed a better separated band pattern than the DCode system and an unambiguous detection of the prevailing species present in the fermentation samples. The most frequent yeast species were Hanseniaspora sp., followed by Pichia kudriavzevii and Saccharomyces cerevisiae, independent of the origin of the cocoa. This indicates a restricted yeast species composition of the cocoa bean fermentation process. Exceptionally, the Ivorian cocoa bean box fermentation samples showed a wider yeast species composition, with Hyphopichia burtonii and Meyerozyma caribbica among the main representatives. Yeasts were not detected in the samples when the temperature inside the fermenting cocoa pulp-bean mass reached values higher than 45 degrees C or under early acetic acid production conditions. PMID- 22093684 TI - Recombinant expression of ShPI-1A, a non-specific BPTI-Kunitz-type inhibitor, and its protection effect on proteolytic degradation of recombinant human miniproinsulin expressed in Pichia pastoris. AB - Pichia pastoris is a highly successful system for the large-scale expression of heterologous proteins, with the added capability of performing most eukaryotic post-translational modifications. However, this system has one significant disadvantage - frequent proteolytic degradation by P. pastoris proteases of heterologously expressed proteins. Several methods have been proposed to address this problem, but none has proven fully effective. We tested the effectiveness of a broad specificity protease inhibitor to control proteolysis. A recombinant variant of the BPTI-Kunitz protease inhibitor ShPI-1 isolated from the sea anemone Stichodactyla helianthus, was expressed in P. pastoris. The recombinant inhibitor (rShPI-1A), containing four additional amino acids (EAEA) at the N terminus, was folded similarly to the natural inhibitor, as assessed by circular dichroism. rShPI-1A had broad protease specificity, inhibiting serine, aspartic, and cysteine proteases similarly to the natural inhibitor. rShPI-1A protected a model protein, recombinant human miniproinsulin (rhMPI), from proteolytic degradation during expression in P. pastoris. The addition of purified rShPI-1A at the beginning of the induction phase significantly protected rhMPI from proteolysis in culture broth. The results suggest that a broad specificity protease inhibitor such as rShPI-1A can be used to improve the yield of recombinant proteins secreted from P. pastoris. PMID- 22093685 TI - Nature and distribution of large sequence polymorphisms in Saccharomyces cerevisiae. AB - To obtain a better understanding of the genome-wide distribution and the nature of large sequence polymorphisms (LSPs) in Saccharomyces cerevisiae, we hybridized genomic DNA of 88 haploid or homozygous diploid S. cerevisiae strains of diverse geographic origins and source substrates onto high-density tiling arrays. On the basis of loss of hybridization, we identified 384 LSPs larger than 500 bp that were located in 188 non-overlapping regions of the genome. Validation by polymerase chain reaction-amplification and/or DNA sequencing revealed that 39 LSPs were due to deletions, whereas 74 LSPs involved sequences diverged far enough from the S288c reference genome sequence as to prevent hybridization to the microarray features. The LSP locations were biased toward the subtelomeric regions of chromosomes, where high genetic variation in genes involved in transport or fermentation is thought to facilitate rapid adaptation of S. cerevisiae to new environments. The diverged LSP sequences appear to have different allelic ancestries and were in many cases identified as Saccharomyces paradoxus introgressions. PMID- 22093686 TI - Auto-aggressive metallic mercury injection around the knee joint: a case report. AB - BACKGROUND: Accidental or intentional subcutaneous and/or intramuscular injection of metallic mercury is an uncommon form of poisoning. Although it does not carry the same risk as mercury vapour inhalation, it may cause destructive early and late reactions. CASE PRESENTATION: Herein we present the case of a 29-year-old male patient who developed an obsessive-compulsive disorder causing auto aggressive behaviour with injection of elemental mercury and several other foreign bodies into the soft tissues around the left knee about 15 years before initial presentation. For clinical examination X-rays and a CT-scan of the affected area were performed. Furthermore, blood was taken to determine the mercury concentration in the blood, which showed a concentration 17-fold higher than recommended. As a consequence, the mercury depots and several foreign bodies were resected marginally. CONCLUSION: Blood levels of mercury will decrease rapidly following surgery, especially in combination with chelating therapy. In case of subcutaneous and intramuscular injection of metallic mercury we recommend marginal or wide excision of all contaminated tissue to prevent migration of mercury and chronic inflammation. Nevertheless, prolonged clinical and biochemical monitoring should be performed for several years to screen for chronic intoxication. PMID- 22093687 TI - Pain and attention - friends or foes? PMID- 22093688 TI - Confusion and ethical issues surrounding the role of Japanese midwives in childbirth and abortion: a qualitative study. AB - This qualitative study describes midwives' experiences in providing care in both pregnancy termination and childbirth in Japan. Midwives working in the general hospital maternity unit assist in both, which is an ethical issue warranting further exploration. Eleven midwives working in a general hospital were interviewed using a semistructured interview, and responses were coded using thematic analysis. Two major themes emerged: the experience of midwives involved in childbirth and pregnancy termination (three subthemes: confusion about care of the baby and aborted fetus, inability to cater to different mothers' needs, and establishing emotional control) and professional awareness and attitude as a midwife (three subthemes: consistency with professional principles, suppression of feelings in relation to aborted fetus, and previous and current professional identities). We found that midwives are isolated in this important social moral issue and its accompanying professional confusion. Suppressing their feelings remains the most common way of dealing with the ambivalence of the roles they fulfill. Improved working conditions and enhanced training on aspects of professional ethics would assist in reducing professional confusion. PMID- 22093689 TI - Overweight and obesity in pediatric liver transplant recipients: prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987-2010. AB - Obesity is extremely common in adult liver transplant recipients and healthy U.S. children. Little is known about the prevalence or risk factors for post transplant obesity in pediatric liver transplant recipients. UNOS data on all U.S. liver transplants 1987-2010 in children 6 months-20 yr at transplant were analyzed. Subjects were categorized as underweight, normal weight, overweight, or obese by CDC guidelines. Predictors of weight status at and after transplant were identified using multivariate logistic regression. Of 3043 children 6-24 months at transplant, 14% were overweight. Of 4658 subjects 2-20 yr at transplant, 16% were overweight and 13% obese. Children overweight/obese at transplant were more likely to be overweight/obese at one, two, and five yr after transplant in all age groups after adjusting for age, ethnicity, primary diagnosis, year of transplant, and transplant type. Weight status at transplant was not associated with overweight/obesity by 10 yr after transplant. The prevalence of post transplant obesity remained high in long-term follow-up, from 20% to 50% depending on age and weight status at transplant. Weight status at transplant is the strongest predictor of post-transplant overweight/obesity. To optimize long term outcomes in pediatric liver transplant recipients, monitoring for obesity and its comorbidities is important. PMID- 22093690 TI - Phenotypic characteristics of hybrid cells generated by transferring neuronal nuclei into bone marrow stromal cell cytoplasts. AB - Bone marrow stromal cells (BMSCs) are promising donor cells for transplantation therapies for a variety of diseases. However, there still lack efficient ways to induce directional differentiation of BMSCs to promote their practical use in transplantation therapy. In this study, we constructed hybrid cells by transferring neuronal nuclei into BMSC cytoplasts and investigated the proliferative capacity and phenotypic characteristics of the hybrid cells. The neuronal nuclei were labeled with Hoechst 33342 before the transfer process, and the cell membrane antigen CD71 was used as a marker of BMSC cytoplasts. The BMSC cytoplasts and neuronal karyoplasts were separated by Ficoll density gradient ultracentrifugation. The hybrid cells were generated by the polyethylene glycol mediated fusion of BMSC cytoplasts with neuronal karyoplasts. The hybrid cells exhibited Hoechst 33342 staining in their nuclei and CD71 staining on their cytomembranes, which confirmed the success of cell fusion. The hybrid cells were positive for BrdU immunostaining. Viability analysis of the cultured hybrid cells by the MTT assay demonstrated their proliferative ability. Immunocytochemical staining revealed the expression of the neuron-specific markers NeuN and MAP2 in the third passage hybrid cells, which indicated their neuronal phenotypic characteristics. The results demonstrated that the hybrid cells produced by fusing neuronal karyoplasts with BMSC cytoplasts had proliferative capability and expressed the neuron-specific markers. Further study is required to investigate the phenotype of the hybrid cells both structurally and functionally. PMID- 22093691 TI - Early manifestations of autism spectrum disorders. Experience of 393 cases in a paediatric neurology. AB - INTRODUCTION: Autism spectrum disorders are group of conditions characterised by qualitative impairments in social communication, interaction, and imagination, and by a restricted range of interests and typical repetitive behaviours. Frequently, there is a delay in the age of detection, and therefore in starting multidisciplinary evaluations and interventions, which may result in a poorer prognosis and reduced quality of life for both children and parents. The aim of our study was to describe clinical and epidemiological data including the age of detection and main initial complaints present in children with autism disorders referred to a paediatric neurology centre. PATIENTS AND METHODS: A total of 393 medical records of consecutive cases diagnosed with an autism spectrum disorder were reviewed. RESULTS: Autism was diagnosed in 82.1% of the cases, unspecified pervasive disorder in 9.9%, Asperger syndrome in 4.8%, and Rett syndrome in 3%. Sixty percent of autistic children presented with a language disorder as their main complaint. The average age of detection was 4 years. CONCLUSIONS: Compared with other countries, age of detection is delayed. Primary care-based screening and surveillance are required in order to improve prognosis and quality of life of children with an autism spectrum disorder. PMID- 22093692 TI - Oxidation of synthetic phenolic antioxidants during water chlorination. AB - The degradation of seven phenolic antioxidants and metabolites during chlorination was investigated. Under strong chlorination conditions (10 mg L(-1) chlorine, 24h), five of the target compounds were significantly degraded, while only BHT-Q (2,6-di-tert-butylcyclohexa-2,5-diene-1,4-dione) and BHT-CHO (3,5-di tert-butyl-4-hydroxybenzaldehyde) were stable. The effect of the presence of bromide to the sample was only significant for BHA (butylated hydroxyanisole) resulting in increased disappearance rate as it is increased. Moreover, the disappearance kinetics were investigated at different concentrations of chlorine and pH of sample using a factorial experimental design. It was observed that the pH of the sample was a significant factor for BHT (butylated hydroxytoluene) and BHA, and chlorine concentration was significant for BHT, resulting in increased disappearance kinetics as they are increased. The degradation of these compounds has revealed two main processes: hydroxylation and oxidation of the aromatic system. The hydroxylated derivatives in some cases (e.g. from BHT-OH (2,6-di-tert butyl-4-(hydroxymethyl)phenol) and BHT-COOH (3,5-di-tert-butyl-4-hydroxybenzoic acid)) are formed via the chlorinated and/or brominated intermediate. Moreover, the oxidation of the aromatic system leads to the quinone derivatives. The investigation of these by-products in real samples by solid-phase extraction-gas chromatography-mass spectrometry (SPE-GC-MS) showed that derivatives of BHT, BHT OH and/or BHT-COOH occurred in wastewater and drinking water samples analysed. PMID- 22093693 TI - Outcomes of surgical repair of double-chambered right ventricle. AB - BACKGROUND: We reviewed our experience with surgical repair of double-chambered right ventricle and long-term outcome. METHODS: From November 1970 to February 2008, repair of double-chambered right ventricle was performed in 61 patients (31 males). The median age was 13 years (interquartile range, 2 months to 64 years); 10 patients were infants (16%). Mean preoperative right ventricular outflow tract pressure gradient was 67+/-37 mm Hg. An associated ventricular septal defect was present in 50 patients (82%). RESULTS: There were 2 (3%) early deaths due to persistence of low cardiac output postoperatively, despite complete relief of the right ventricular gradient. The overall mean postoperative gradient was 2+/-4.5 mm Hg. Late follow-up was complete in 92% (mean, 7.4+/-7.9 years; maximum, 37 years). Late survival was 90% at 10 years. There were 3 late deaths due to heart failure in 2 patients and sudden death in 1 patient, all occurring before 1997. No patients required reoperation for residual or recurrent right ventricular obstruction. CONCLUSIONS: Surgical correction of double-chambered right ventricle results in excellent functional and hemodynamic long-term results, with complete relief of the right ventricular obstruction. The presence of a double-chambered right ventricle should be considered in anomalies with high or persistent right ventricular outflow tract obstruction. PMID- 22093694 TI - Moderate tricuspid regurgitation with left-sided degenerative heart valve disease: to repair or not to repair? AB - BACKGROUND: Uncertainty about long-term effects of surgically unaddressed moderate (2+) secondary tricuspid valve (TV) regurgitation (TR) accompanying left sided degenerative heart valve disease led us to identify reasons for and factors associated with TV repair, compare safety and clinical effectiveness of relieving TR, and identify factors associated with severe (3/4+) postoperative TR. METHODS: From 1997 to 2008, 1,724 patients with 2+ TR underwent 830 mitral, 703 aortic, and 191 double-valve procedures; 91 (5%) had concomitant TV repair. Logistic regression analysis was used to identify factors associated with TV repair and for propensity-matched comparison of safety (in-hospital morbidity, mortality) and effectiveness of TV repair (longitudinal echocardiographic assessment of postoperative TR and New York Heart Association class, TV intervention, survival). RESULTS: Factors associated with TV repair of 2+ TR included larger right ventricles and left ventricles (p<0.001), greater TV tethering height (p=0.0002), and prior concurrent mitral valve procedures (p<=0.004). In-hospital complications, subsequent TV interventions, and intermediate-term survival were similar for matched patients. The TV repair patients had less 3/4+ TR at discharge (7% versus 15%), sustained out to 3 years. No TV repair (p=0.05), female sex (p<0.0001), and mitral valve replacement (p=0.008) were associated with 3/4+ TR. CONCLUSIONS: A TV repair for moderate TR concomitant with surgery for degenerative left-sided heart valve disease is reasonable to provide an opportunity to prevent its progression and development of right ventricle dysfunction, particularly for patients with important right ventricle remodeling and evidence of right ventricular failure, and for patients with advanced left sided disease requiring mitral valve replacement. PMID- 22093695 TI - Analysis of osteopontin levels for the identification of asymptomatic patients with calcific aortic valve disease. AB - BACKGROUND: Calcific aortic valve disease (CAVD) is the most common cause of acquired valve disease. Initial phases of CAVD include thickening of the cusps, whereas advanced stages are associated with biomineralization and reduction of the aortic valve area. These conditions are known as aortic valve sclerosis (AVSc) and aortic valve stenosis (AVS), respectively. Because of its asymptomatic presentation, little is known about the molecular determinants of AVSc. The aim of this study was to correlate plasma and tissue osteopontin (OPN) levels with echocardiographic evaluation for the identification of asymptomatic patients at risk for CAVD. In addition, our aim was to analyze the differential expression and biological function of OPN splicing variants as biomarkers of early and late stages of CAVD. METHODS: From January 2010 to February 2011, 310 patients were enrolled in the study. Patients were divided into 3 groups based on transesophageal echocardiographic (TEE) evaluation: controls (56 patients), AVSc (90 patients), and AVS (164 patients). Plasma and tissue OPN levels were measured by immunohistochemical evaluation, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (qPCR). RESULTS: Patients with AVSc and AVS have higher OPN levels compared with controls. OPN levels are elevated in asymptomatic patients with AVSc with no appearance of calcification during TEE evaluation. OPN splicing variants OPN-a, OPN-b, and OPN-c are differentially expressed during CAVD progression and are able to inhibit biomineralization in a cell-based biomineralization assay. CONCLUSIONS: The analysis of the differential expression of OPN splicing variants during CAVD may help in developing diagnostic and risk stratification tools to follow the progression of asymptomatic aortic valve degeneration. PMID- 22093696 TI - Cloning, expression and antiviral activity of IFNgamma from the Australian fruit bat, Pteropus alecto. AB - Bats are natural reservoir hosts to a variety of viruses, many of which cause morbidity and mortality in other mammals. Currently there is a paucity of information regarding the nature of the immune response to viral infections in bats, partly due to a lack of appropriate bat specific reagents. IFNgamma plays a key role in controlling viral replication and coordinating a response for long term control of viral infection. Here we describe the cloning and expression of IFNgamma from the Australian flying fox, Pteropus alecto and the generation of mouse monoclonal and chicken egg yolk antibodies specific to bat IFNgamma. Our results demonstrate that P. alecto IFNgamma is conserved with IFNgamma from other species and is induced in bat splenocytes following stimulation with T cell mitogens. P. alecto IFNgamma has antiviral activity on Semliki forest virus in cell lines from P. alecto and the microbat, Tadarida brasiliensis. Additionally recombinant bat IFNgamma was able to mitigate Hendra virus infection in P. alecto cells. These results provide the first evidence for an antiviral role for bat IFNgammain vitro in addition to the application of important immunological reagents for further studies of bat antiviral immunity. PMID- 22093699 TI - Transactivation of ABCG2 through a novel cis-element in the distal promoter by constitutive androstane receptor but not pregnane X receptor in human hepatocytes. AB - A previous report demonstrated that treatment of human hepatocytes with phenobarbital, an activator of nuclear receptor constitutive androstane receptor (CAR), increases mRNA levels of an efflux transporter ABCG2, which is involved in the excretion of xenobiotics in liver and intestine. The results suggest that human CAR (hCAR) transactivates human ABCG2 (hABCG2) expression. In this study, we confirmed increase in ABCG2 mRNA levels in human hepatocytes after adenoviral expression of hCAR and treatment with its activator. Reporter assays suggested the existence of an hCAR-responsive element between -8000 and -7485 of hABCG2 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays identified a DR5 motif (direct repeat separated by five nucleotides) within the region as a binding motif of hCAR/human retinoid X receptor alpha heterodimer. The introduction of mutations into the DR5 motif resulted in the complete loss of the hCAR-mediated transactivation. Interestingly, human pregnane X receptor, belonging to the same NR1I subfamily as CAR, did not activate any reporter gene containing the DR5 motif. Taken together, our present findings suggest that hCAR transactivates hABCG2 through the DR5 motif located in its distal promoter in human hepatocytes and that the motif prefers hCAR to pregnane X receptor. PMID- 22093698 TI - New insights into the metabolism of organomercury compounds: mercury-containing cysteine S-conjugates are substrates of human glutamine transaminase K and potent inactivators of cystathionine gamma-lyase. AB - Anthropogenic practices and recycling in the environment through natural processes result in release of potentially harmful levels of mercury into the biosphere. Mercury, especially organic forms, accumulates in the food chain. Mercury reacts readily with sulfur-containing compounds and often exists as a thiol S-conjugate, such as the l-cysteine (Cys)-S-conjugate of methylmercury (CH(3)Hg-S-Cys) or inorganic mercury (Cys-S-Hg-S-Cys). These S-conjugates are structurally similar to l-methionine and l-cystine/l-cystathionine, respectively. Bovine and rat glutamine transaminase K (GTK) catalyze transamination of sulfur containing amino acids. Recombinant human GTK (rhGTK) has a relatively open catalytic active site, and we report here that this enzyme, like the rat and bovine enzymes, can also utilize sulfur-containing l-amino acids, including l methionine, l-cystine, and l-cystathionine as substrates. The current study extends this list to include mercuric S-conjugates, and shows that CH(3)Hg-S-Cys and Cys-S-Hg-S-Cys are substrates and reversible inhibitors of rhGTK. The homocysteine S-conjugates, Hcy-S-Hg-S-Hcy and CH(3)Hg-S-Hcy, are also inhibitors. Finally, we show that HgCl(2), CH(3)Hg-S-Cys and Cys-S-Hg-S-Cys are potent irreversible inhibitors of rat cystathionine gamma-lyase. The present study broadens our knowledge of the biochemistry of mercury compounds by showing that Cys S-conjugates of mercury interact with enzymes that catalyze transformations of biologically important sulfur-containing amino acids. PMID- 22093700 TI - [How are the hypothesis and the objectives established in a Radiology research project?]. AB - Research is a systematic process designed to answer a question. This is the starting point of the whole project and specifically formulates a problem observed in the analysis of the reality. The answer to this attempts to clarify an uncertainty in our knowledge. The conceptual hypothesis is the theoretical answer to the question set out. The operational hypothesis is the particular form that which sets out to demonstrate the conceptual hypothesis. The objectives are the justification for conducting the research. They help to define what it attempts to obtain, and what answers it will give to the formulated questions. It must show a clear and consistent relationship with the description of the problem and, specifically, with the questions and/or hypothesis that are to be resolved. PMID- 22093697 TI - At the membrane frontier: a prospectus on the remarkable evolutionary conservation of polyprenols and polyprenyl-phosphates. AB - Long-chain polyprenols and polyprenyl-phosphates are ubiquitous and essential components of cellular membranes throughout all domains of life. Polyprenyl phosphates, which include undecaprenyl-phosphate in bacteria and the dolichyl phosphates in archaea and eukaryotes, serve as specific membrane-bound carriers in glycan biosynthetic pathways responsible for the production of cellular structures such as N-linked protein glycans and bacterial peptidoglycan. Polyprenyl-phosphates are the only form of polyprenols with a biochemically defined role; however, unmodified or esterified polyprenols often comprise significant percentages of the cellular polyprenol pool. The strong evolutionary conservation of unmodified polyprenols as membrane constituents and polyprenyl phosphates as preferred glycan carriers in biosynthetic pathways is poorly understood. This review surveys the available research to explore why unmodified polyprenols have been conserved in evolution and why polyprenyl-phosphates are universally and specifically utilized for membrane-bound glycan assembly. PMID- 22093701 TI - Homicide and bipolar I disorder: a 22-year study. AB - BACKGROUND: Non-serious offenses in manic phase have been mainly studied in patients with bipolar disorder. However, some authors reported that depressive phase is related with the violent and homicidal manifestations of bipolar disorder. AIMS: We investigated the characteristics of homicide by the polarity of mood episode in patients with bipolar I disorder. METHODS: Among the offenders who were sentenced to undergo treatment at the National Institute of Forensic Psychiatry from October 1987 to January 2008, a total 219 offenders whose final diagnoses were bipolar I disorder based on DSM-III-R and DSM-IV were selected. Retrospective medical chart review was performed for characteristics of mood episodes. Descriptions of offenders were supplemented by review of the written records of the police or prosecutors. RESULTS: The general rate of total offense was higher in the manic phase than in the depressive phase (86.8% vs. 13.2%). However, the rate of homicide was higher in the depressive phase than in the manic phase. The victims of homicide were more likely to be family members of the patients in depressive phase than in manic phases (96.2% vs. 63.9%, p=0.001). However, parricide was committed only in manic phases. Altruistic motivation of homicide was significantly higher in depressive phase (34.6% vs. 0%, p<0.001) whereas impulsivity was the most common one in manic phases. CONCLUSIONS: The risk of offenses, particularly homicide for family members, should not be overlooked in the depressive phases of bipolar I disorder. PMID- 22093702 TI - A real-time PCR assay for the relative quantification of the tetrahydrocannabinolic acid (THCA) synthase gene in herbal Cannabis samples. AB - In this study, we wanted to investigate whether or not the tetrahydrocannabinolic acid (THCA) synthase gene, which codes for the enzyme involved in the biosynthesis of THCA, influences the production and storage of tetrahydrocannabinol (THC) in a dose-dependent manner. THCA is actually decarboxylated to produce THC, the main psychoactive component in the Cannabis plant. Assuming as the research hypothesis a correlation between the gene copy number and the production of THC, gene quantification could be useful in forensics in order to complement or replace chemical analysis for the identification and classification of seized Cannabis samples, thus distinguishing the drug-type from the fibre-type varieties. A real-time PCR assay for the relative quantification of the THCA synthase gene was then validated on Cannabis samples; some were seized from the illegal drug market and others were derived from experimental cultivation. In order to determine the gene copy number to compare high vs. low potency plants, we chose the DeltaDeltaCt method for TaqMan reactions. The assay enabled single plants with zero, one, and two copies of the gene to be distinguished. As a result of this first part of the research on the THCA synthase gene (the second part will cover a study of gene expression), we found no correlation between THCA synthase gene copy number and the content of THC in the herbal Cannabis samples tested. PMID- 22093703 TI - Significantly increased detection rate of drugs of abuse in urine following the introduction of new German driving licence re-granting guidelines. AB - In this paper we present the first assessment of the new German driving licence re-granting medical and psychological assessment (MPA) guidelines by comparing over 3500 urine samples tested under the old MPA cut-offs to over 5000 samples tested under the new MPA cut-offs. Since the enzyme multiplied immunoassay technique (EMIT) technology used previously was not sensitive enough to screen for drugs at such low concentrations, as suggested by the new MPA guidelines, enzyme-linked immunosorbent assay (ELISA) screening kits were used to screen for the drugs of abuse at the new MPA cut-offs. The above comparison revealed significantly increased detection rates of drug use or exposure during the rehabilitation period as follows: 1.61, 2.33, 3.33, and 7 times higher for 11-nor delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), morphine, benzoylecgonine and amphetamine respectively. The present MPA guidelines seem to be more effective to detect non-abstinence from drugs of abuse and hence to detecting drivers who do not yet fulfil the MPA requirements to regain their revoked driving licence. PMID- 22093704 TI - Pyrolysis of polyolefins for increasing the yield of monomers' recovery. AB - Pyrolysis of plastic waste is an alternative way of plastic recovery and could be a potential solution for the increasing stream of solid waste. The objective of this work was to increase the yield the gaseous olefins (monomers) as feedstock for polymerization process and to test the applicability of a commercial Ziegler Natta (Z-N): TiCl(4)/MgCl(2) for cracking a mixture of polyolefins consisted of 46%wt. of low density polyethylene (LDPE), 30%wt. of high density polyethylene (HDPE) and 24%wt. of polypropylene (PP). Two sets of experiments have been carried out at 500 and 650 degrees C via catalytic pyrolysis (1% of Z-N catalyst) and at 650 and 730 degrees C via only-thermal pyrolysis. These experiments have been conducted in a lab-scale, fluidized quartz-bed reactor of a capacity of 1 3kg/h at Hamburg University. The results revealed a strong influence of temperature and presence of catalyst on the product distribution. The ratios of gas/liquid/solid mass fractions via thermal pyrolysis were: 36.9/48.4/15.7%wt. and 42.4/44.7/13.9%wt. at 650 and 730 degrees C while via catalytic pyrolysis were: 6.5/89.0/4.5%wt. and 54.3/41.9/3.8%wt. at 500 and 650 degrees C, respectively. At 650 degrees C the monomer generation increased by 55% up to 23.6%wt. of total pyrolysis products distribution while the catalyst was added. Obtained yields of olefins were compared with the naphtha steam cracking process and other potentially attractive processes for feedstock generation. The concept of closed cycle material flow for polyolefins has been discussed, showing the potential benefits of feedstock recycling in a plastic waste management. PMID- 22093705 TI - Eco-efficient waste glass recycling: Integrated waste management and green product development through LCA. AB - As part of the EU Life + NOVEDI project, a new eco-efficient recycling route has been implemented to maximise resources and energy recovery from post-consumer waste glass, through integrated waste management and industrial production. Life cycle assessment (LCA) has been used to identify engineering solutions to sustainability during the development of green building products. The new process and the related LCA are framed within a meaningful case of industrial symbiosis, where multiple waste streams are utilised in a multi-output industrial process. The input is a mix of rejected waste glass from conventional container glass recycling and waste special glass such as monitor glass, bulbs and glass fibres. The green building product is a recycled foam glass (RFG) to be used in high efficiency thermally insulating and lightweight concrete. The environmental gains have been contrasted against induced impacts and improvements have been proposed. Recovered co-products, such as glass fragments/powders, plastics and metals, correspond to environmental gains that are higher than those related to landfill avoidance, whereas the latter is cancelled due to increased transportation distances. In accordance to an eco-efficiency principle, it has been highlighted that recourse to highly energy intensive recycling should be limited to waste that cannot be closed-loop recycled. PMID- 22093706 TI - Co-gasification of municipal solid waste and material recovery in a large-scale gasification and melting system. AB - This study evaluates the effects of co-gasification of municipal solid waste with and without the municipal solid waste bottom ash using two large-scale commercial operation plants. From the viewpoint of operation data, there is no significant difference between municipal solid waste treatment with and without the bottom ash. The carbon conversion ratios are as high as 91.7% and 95.3%, respectively and this leads to significantly low PCDD/DFs yields via complete syngas combustion. The gross power generation efficiencies are 18.9% with the bottom ash and 23.0% without municipal solid waste bottom ash, respectively. The effects of the equivalence ratio are also evaluated. With the equivalence ratio increasing, carbon monoxide concentration is decreased, and carbon dioxide and the syngas temperature (top gas temperature) are increased. The carbon conversion ratio is also increased. These tendencies are seen in both modes. Co-gasification using the gasification and melting system (Direct Melting System) has a possibility to recover materials effectively. More than 90% of chlorine is distributed in fly ash. Low-boiling-point heavy metals, such as lead and zinc, are distributed in fly ash at rates of 95.2% and 92.0%, respectively. Most of high-boiling-point heavy metals, such as iron and copper, are distributed in metal. It is also clarified that slag is stable and contains few harmful heavy metals such as lead. Compared with the conventional waste management framework, 85% of the final landfill amount reduction is achieved by co-gasification of municipal solid waste with bottom ash and incombustible residues. These results indicate that the combined production of slag with co-gasification of municipal solid waste with the bottom ash constitutes an ideal approach to environmental conservation and resource recycling. PMID- 22093707 TI - Clinical features and risk factors of tuberculosis in living-donor liver transplant recipients. AB - BACKGROUND: The incidence of active tuberculosis (TB) among liver transplant recipients varies depending on the endemic area and various reported TB risk factors. Although living-donor liver transplantation (LDLT) is predominant in Japan, the TB incidence and risk factors among LDLT recipients are unknown. METHODS: Active TB episodes among 1222 LDLT recipient cases from 1990 to 2007 were retrospectively reviewed. A matched case-control study was performed to identify risk factors for active TB infection. RESULTS: Nine patients (0.74%, 5 males and 4 females, median age 48 years) developed active TB following LDLT. The incidence of TB in adults (over 18 years) and in the later cohort (2000-2007) was more than that of children and in the early cohort (1990-1999), respectively. Seven of 9 patients were diagnosed within 1 year after LDLT. No patient received isoniazid for latent TB infection treatment before transplantation. TB infection was controlled with anti-tuberculous drugs in all affected patients. However, 2 patients died of graft failure. Univariate analyses identified severe Child-Pugh score (>= 11) (P = 0.006; odds ratio [OR], 10.0; 95% confidence interval [CI], 1.9-51.5), requirement for plasma exchange or plasmapheresis (P = 0.009; OR, 10.0; 95% CI, 1.9-53.4), and ABO-incompatible transplantation (P = 0.0003; OR, 34.0; 95% CI, 4.7-248.3) as risk factors for onset of active TB infection. CONCLUSIONS: Patients having an elevated Child-Pugh score, plasma exchange or plasmapheresis, and ABO-incompatible transplantation should be considered at greater risk for active TB infection, and treatment for latent TB infection before transplantation should be considered. PMID- 22093709 TI - Perspectives on steroid metabolism in marine organisms. PMID- 22093708 TI - Human HERC5 restricts an early stage of HIV-1 assembly by a mechanism correlating with the ISGylation of Gag. AB - BACKGROUND: The identification and characterization of several interferon (IFN) induced cellular HIV-1 restriction factors, defined as host cellular proteins or factors that restrict or inhibit the HIV-1 life cycle, have provided insight into the IFN response towards HIV-1 infection and identified new therapeutic targets for HIV-1 infection. To further characterize the mechanism underlying restriction of the late stages of HIV-1 replication, we assessed the ability of IFNbeta induced genes to restrict HIV-1 Gag particle production and have identified a potentially novel host factor called HECT domain and RCC1-like domain-containing protein 5 (HERC5) that blocks a unique late stage of the HIV-1 life cycle. RESULTS: HERC5 inhibited the replication of HIV-1 over multiple rounds of infection and was found to target a late stage of HIV-1 particle production. The E3 ligase activity of HERC5 was required for blocking HIV-1 Gag particle production and correlated with the post-translational modification of Gag with ISG15. HERC5 interacted with HIV-1 Gag and did not alter trafficking of HIV-1 Gag to the plasma membrane. Electron microscopy revealed that the assembly of HIV-1 Gag particles was arrested at the plasma membrane, at an early stage of assembly. The mechanism of HERC5-induced restriction of HIV-1 particle production is distinct from the mechanism underlying HIV-1 restriction by the expression of ISG15 alone, which acts at a later step in particle release. Moreover, HERC5 restricted murine leukemia virus (MLV) Gag particle production, showing that HERC5 is effective in restricting Gag particle production of an evolutionarily divergent retrovirus. CONCLUSIONS: HERC5 represents a potential new host factor that blocks an early stage of retroviral Gag particle assembly. With no apparent HIV-1 protein that directly counteracts it, HERC5 may represent a new candidate for HIV/AIDS therapy. PMID- 22093710 TI - Tributes to cardiac surgical pioneers. PMID- 22093713 TI - Mediastinoscopy: an obsolete procedure? PMID- 22093712 TI - 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. PMID- 22093714 TI - Esophageal submucosa: the watershed for esophageal cancer. AB - OBJECTIVES: Submucosal esophageal cancers (pT1b) are considered superficial, implying good survival. However, some are advanced, metastasizing to regional lymph nodes. Interplay of cancer characteristics and lymphatic anatomy may create a watershed, demarcating low-risk from high-risk cancers. Therefore, we characterized submucosal cancers according to depth of invasion and identified those with high likelihood of lymph node metastases and poor survival. METHODS: From 1983 to 2010, 120 patients underwent esophagectomy for submucosal cancers at Cleveland Clinic. Correlations were sought among cancer characteristics (location, dimensions, histopathologic cell type, histologic grade, and lymphovascular invasion [LVI]), and their associations with lymph node metastasis were identified by logistic regression. Associations with mortality were identified by Cox regression. RESULTS: As submucosal invasion increased, cancer length (P < .001), width (P < .001), area (P < .001), LVI (P = .007), and grade (P = .05) increased. Invasion of the deep submucosa (P < .001) and LVI (P = .06) predicted lymph node metastases: 45% (23/51) of deep versus 10% (3/29) of middle third and 7.5% (3/40) of inner-third cancers had lymph node metastases, as did 46% (12/26) with LVI versus 18% (17/94) without. Older age and lymph node metastases predicted worse 5-year survival: 94% for younger pN0 patients, 62% for older pN0 patients, and 36% for pN1-2 patients regardless of age. CONCLUSIONS: Submucosal cancer characteristics and lymphatic anatomy create a watershed for regional lymph node metastases in the deep submucosa. This previously unrecognized divide distinguishes superficial submucosal cancers with good survival from deep submucosal cancers with poor survival. Aggressive therapy of more superficial cancers is critical before submucosal invasion occurs. PMID- 22093716 TI - Femoral artery cannulation for thoracic aortic surgery: safe under transesophageal echocardiographic control. AB - OBJECTIVE: Choice of cannulation site (femoral, axillary) for cardiopulmonary bypass for thoracic aortic surgery is controversial. We review a single-center consecutive experience with femoral cannulation in the era of transesophageal echocardiography (TEE). METHODS: Femoral artery cannulation is our preference for both aneurysms and dissections. If intraoperative TEE (or preoperative computed tomography) shows mobile atheroma, we avoid femoral cannulation and use the right axillary artery. Charts were reviewed to detect any cannulation- or perfusion related complications. RESULTS: Eight hundred eighty patients underwent cannulation for cardiopulmonary bypass for thoracic aortic surgery: 767 femoral (87%) and 113 other (13%, 87 aortic, 22 axillary, 4 innominate). Among the femoral cases, 673 (87.7%) were elective and 94 (12.2%) urgent or emergency. Hospital survival was 723 of 767 (94%): 654 of 673 (97%) for elective cases and 69 of 94 (73%) for urgent or emergency cases. Survivals were 549 of 572 (95%) for ascending and arch, 91 of 97 (93%) for descending, and 83 of 98 (84%) for thoracoabdominal. Stroke (fixed neurologic deficit) occurred in 14 of 767 cases (1.8%): 9 ascending or arch and 5 descending or thoracoabdominal. There were 5 paraplegias in the descending or thoracoabdominal group. There was 1 instance of intraoperative descending dissection (well tolerated), no arterial ruptures, and 6 instances (0.7%) of local femoral arterial narrowing requiring surgical correction (patch graft). One patient (0.1%) had postoperative ischemia of the cannulated limb, and 25 patients (3.2%) had local wound problems (infection 21, seroma 4) treated conservatively. CONCLUSIONS: This large experience in the TEE era strongly supports femoral cannulation for aortic surgery, with good survival, low stroke rate, minimal perfusion-related rupture or dissection, and minimal limb ischemia. If intraoperative TEE shows mobile atheroma, axillary cannulation is preferred. PMID- 22093717 TI - The hazard of comparing apples and oranges: the proper indication for the use of recombinant activated clotting factor VII in cardiac surgery. PMID- 22093719 TI - Cannulation sites and types for antegrade cerebral perfusion during arch surgery. PMID- 22093722 TI - Dabigatran etexilate in mechanical valve thromboprophylaxis. PMID- 22093723 TI - 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. PMID- 22093726 TI - [Development and challenge of neuroendoscopic surgery]. PMID- 22093724 TI - Circulating angiogenic cell populations, vascular function, and arterial stiffness. AB - OBJECTIVE: Several bone marrow-derived cell populations have been identified that may possess angiogenic activity and contribute to vascular homeostasis in experimental studies. We examined the extent to which lower quantities of these circulating angiogenic cell phenotypes may be related to impaired vascular function and greater arterial stiffness. METHODS: We studied 1948 Framingham Heart Study participants (mean age, 66+/-9 years; 54% women) who were phenotyped for circulating angiogenic cells: CD34+, CD34+/KDR+, and early outgrowth colony forming units (CFU). Participants underwent non-invasive assessments of vascular function including peripheral arterial tone (PAT), arterial tonometry, and brachial reactivity testing. RESULTS: In unadjusted analyses, higher CD34+ and CD34+/KDR+ concentrations were modestly associated with lower PAT ratio (beta= 0.052+/-0.011, P<0.001 and beta=-0.030+/-0.011, P=0.008, respectively) and with higher carotid-brachial pulse wave velocity (beta=0.144+/-0.043, P=0.001 and beta=0.112+/-0.043, P=0.009), but not with flow-mediated dilation; higher CD34+ was also associated with lower carotid-femoral pulse wave velocity (beta=-0.229+/ 0.094, P=0.015). However, only the association of lower CD34+ concentration with higher PAT ratio persisted in multivariable analyses that adjusted for standard cardiovascular risk factors. In all analyses, CFU was not associated with measures of vascular function or arterial stiffness. CONCLUSIONS: In our large, community-based sample of men and women, circulating angiogenic cell phenotypes largely were not associated with measures of vascular function or arterial stiffness in analyses adjusting for traditional risk factors. PMID- 22093725 TI - News from the literature: focus on joint ESC/EAS dyslipidemia guidelines. PMID- 22093727 TI - [Neuroendoscopic treatment for 372 cases of intracranial lesions]. AB - OBJECTIVE: To explore the application of neuroendoscopic treatment for intracranial lesions. METHODS: The clinic data of 372 patients with intracranial lesions, who underwent neuroendoscopic treatment at our department from May 1998 to May 2010, were reviewed retrospectively. Representative endoscopic treatments included endoscopic third ventriculostomy (ETV) (n = 198), ETV & endoscopic biopsy (n = 69), neuroendoscopic ostomy for septum pellucidum fenestration (n = 55) (for septum pellucidum cysts, n = 37) and endoscopic cystoventriculostomy for ventricular cysts (n = 50). Their surgical indications and clinical outcomes were summarized for analysis. RESULTS: ETV was performed successfully in 369 cases. Among them, 2 failed cases underwent other operations and endoscopic biopsy failed in 1 case. Within a short post-operative period, the symptoms were resolved in 347 cases (93.3%), showed no improvement in 23 cases (6.2%) and 2 died (0.5%). At Month 6 post-operation, a failure of ETV was detected in 22 cases (9.5%), a failure of neuroendoscopic ostomy for septum pellucidum cysts in 23 (69.7%) and for ventricular cysts in 12 cases (26.7%). CONCLUSION: ETV is effective in the treatment of obstructive hydrocephalus, but its indication should be strictly controlled for children. Effective rate of neuroendoscopic treatment for intracranial septum pellucidum cysts remains unsatisfactory so that its operative indication should be strictly controlled. PMID- 22093728 TI - [Application of neuroendoscope in the treatment of skull base chordoma]. AB - OBJECTIVE: To further explore the application, approach, indication and prognosis of neuroendoscope treatment for skull base chordoma. METHODS: A total of 101 patients of skull base chordoma were admitted at our hospital from May 2000 to April 2010. There were 59 males and 42 females. Their major clinical manifestations included headache, cranial nerve damage and dyspnea. They were classified according to the patterns of tumor growth: Type I (n = 13): tumor location at a single component of skull base, i. e. clivus or sphenoid sinus with intact cranial dura; Type II (n = 56): tumor involving more than two components of skull e. g clivus, sphenoid and nasal/oral cavity, etc. But there was no intracranial invasion; Type III (n = 32) : tumor extending widely and intradurally forming compression of brain stems and multiple cranial nerves. Based on the types of chordoma, different endoscopic approaches were employed, viz. transnasal, transoral, trans-subtemporal fossa and plus microsurgical craniotomy for staging in some complex cases. RESULTS: Among all patients, total resection was achieved (n = 19), subtotal (n = 58) and partial (n = 24). In partial resection cases, 16 cases were considered to be subtotal due to a second stage operation. Most cases had conspicuous clinical improvements. Self-care recovery within one week post-operation accounted for 58.4%, two weeks 30.7%, one month 6.9% and more than one month 1.9%. Postoperative complications occurred in 13 cases (12.8%) and included CSF leakage (n = 4) cranial nerve palsy (n = 5), hemorrhagic nasal wounds (n = 3) and delayed intracranial hemorrhage (n = 1). All of these were cured or improved after an appropriate treatment. A follow-up of 6 60 months was conducted in 56 cases. CONCLUSION: Early detection and early treatment are crucial for achieving a better outcome in chordoma. Neuroendoscopic treatment plays an important role in managing those complicated cases. Precise endoscopic techniques plus different surgical approaches and staging procedures are required to improve the post-operative quality of life for patients. PMID- 22093729 TI - [Repairing front skull base and saddle bottom of cerebrospinal fluid rhinorrhea under endoscopy]. AB - OBJECTIVE: To explore the methods and techniques of repairing cerebrospinal fluid (CSF) rhinorrhea and reconstructing the defects of skull base under endoscopy. METHODS: The clinical data of 26 patients undergoing endoscopic repair of CSF rhinorrhea were analyzed retrospectively. There were 19 males and 7 females with an average age of 31.5 years old. Rhinorrhea was classified into 4 types: ethmoidal sinus type (n = 6), sphenoid sinus type (n = 14) and mixed type (n = 6) and frontal sinus type (n = 0). RESULTS: The causes of rhinorrhea were as follows: traumatic leakage (n = 17), post-operative breakage of saddle area (n = 6), damage after endonasal surgery (n = 2) rhinorrhea after gamma-knife for pituitary (n = 1). All cases were successfully repaired via an endoscopic endonasal approach. Among them, 22 patients were repaired only once while 4 patients with recurrent CSF rhinorrhea were repaired again. The follow-up period was from 6 months to 4 years. And satisfactory outcomes were achieved in all. CONCLUSION: Accurate localization of CSF leakage, reliable reconstruction of skull base, secure fixation of adhesive materials and continuous lumbar CSF drainage are keys surgical techniques. Endoscopic repair of front skull base and saddle bottom of CSF rhinorrhea is a reliable, effective and mini-invasive surgical approach worth further popularization. PMID- 22093730 TI - [Neuroendoscopic treatment of different types of quadrigeminal cistern arachnoid cysts]. AB - OBJECTIVE: To evaluate the method, strategy and efficacy of treating different types of quadrigeminal cistern arachnoid cysts (QCAC) with neuroendoscope. METHODS: A retrospective analysis was conducted for 12 QCAC patients with obstructive hydrocephalus. They were classified into 3 types and underwent neuroendoscopic operation at our hospital between November 2005 and November 2009. Their surgical approaches, complications and efficacy were analyzed. The mean age of first diagnosis was 3.7 years old. There were 7 type II cases and 5 type III cases with a varying level of symptoms. The follow-up period was 6 - 24 months. Cine-MRI (magnetic resonance imaging) examination was performed both preoperatively and post-operatively. RESULTS: Among them, 12 patients recovered well without any occurrence of hemorrhage, paralysis, lower cranial nerve injury, cerebrospinal fluid leakage, infection or death. Subdural effusion occurred in 3 cases, but disappeared within 6 months. Seven feverish cases recovered after a symptomatic treatment. The shapes of cysts and ventricles almost returned to a normal level in 8 cases. Three cases of arachnoid cyst had a slight change. CONCLUSION: In accordance with the QCAC patient types, different neuroendoscopic approaches can fully reconstruct the cerebrospinal fluid circulation. And the use of frameless navigation makes it more precise and safe. PMID- 22093731 TI - [Neuroendoscopic management of tethered spinal cord syndrome]. AB - OBJECTIVE: To investigate the methods and efficacy of neuroendoscopic operation in the treatment of tethered spinal cord syndrome (TSCS). METHODS: A total of 21 cases were recruited. There were 13 males and 8 females with an average age of 12.5 years old. TSCS was diagnosed by magnetic resonance imaging (MRI). They were operated under neuroendoscope. RESULTS: No complication was found during a follow up period of 0.5 - 3 years. The symptoms improved in 18 cases. Neither obvious improvement nor aggravation was found in 3 cases. The total effective rate was 85.71%. CONCLUSION: Neuroendoscopic treatment of TSCS is both safe and effective. PMID- 22093732 TI - [Evaluation of risk factors for retinopathy of prematurity]. AB - OBJECTIVE: To evaluate the incidence and risk factors of ROP (retinopathy of prematurity) through a prospective multicenter study. METHODS: Eleven children's or maternal & child hospitals participated in a collective network. All infants of birth weight < 2000 g, born in or transferred to one of the participating centers from January 1st 2005 to February 28th 2006 were recruited. Timely ophthalmologic examinations were performed. The relevant data at baseline and endpoints were collected at each unit. RESULTS: A total of 882 preterm infants fulfilled the screening criteria and 752 finished a followup. And 123 infants (16.4%) had some degree of ROP. Infants with ROP had a lower gestational age, birth weight and a longer duration of oxygen versus those without ROP [(30.82 +/- 0.20) weeks vs (32.56 +/- 0.09) weeks, (1430 +/- 25) g vs (1636 +/-10) g, (11.6 +/- 1.4) d vs (4.4 +/- 0.3) d]. Through a univariate analysis, birth weight, gestational age, asphyxia, oxygen duration > 5 days, apnea, surfactant usage, pneumonia, anemia, blood transfusion, acidosis and neonatal respiratory distress syndrome (NRDS) were associated with ROP (P < 0.05). Logistic regression analysis showed that birth weight (OR = 0.998), apnea (OR = 1.653) and blood transfusion (OR = 1.763) were independent risk factors for ROP. CONCLUSION: Asphyxia, oxygen duration > 5 days, surfactant usage, anemia, acidosis and NRDS, lower birth weight, apnea and blood transfusion may improve the risks of ROP. PMID- 22093733 TI - [Plasma homocysteine levels in ischemic stroke patients with obstructive sleep apnea]. AB - OBJECTIVE: To investigate the association of plasma homocysteine and OSA (obstructive sleep apnea) syndrome in ischemic stroke (IS). METHODS: A total of 92 male IS patients were classified by apnea hypopnea index (AHI) into 2 groups: non-OSA group (AHI < 5/h) and OSA group (AHI > or = 5). All patients were tested for plasma homocysteine when polysomnography was finished at (14 +/- 2) d after the onset of IS. RESULTS: The mean level of homocysteine was significantly higher in the OSA group than that in the non-OSA group (17 +/- 5 vs 11 +/- 3 micromol/L, P < 0.01). Pearson correlation analysis revealed a positive correlation between the homocysteine level and the severity of AHI (r = 0.482, P < 0.01). Further multiple linear regression analysis showed that AHI and folate were independent predictors of homocysteine level (R2 = 0.553, P < 0.01, beta for AHI = 0.671, beta for folate = -0.256). CONCLUSION: The severity of OSA is significantly associated with an elevated level of homocysteine in IS patients. And this association is independent of other causative factors of an elevated level of homocysteine. PMID- 22093734 TI - [Analysis of etiological and related factors responsible for acute gastrointestinal hemorrhage]. AB - OBJECTIVE: To investigate the etiology, related factors and endoscopic characteristics of acute gastrointestinal hemorrhage. METHODS: The data including age, gender, medical and medication history, and endoscopic characteristics of patients receiving emergency treatment for acute gastrointestinal hemorrhage between February 2006 and February 2010 were collected to analyze the etiological profiles of this disorder. RESULTS: (1) A total of 1415 patients with a 2: 1 male to-female ratio visited our hospital for acute gastrointestinal hemorrhage in the past 4 years. There was a higher mean age of disease onset in men than in women [(51 +/- 20) years old vs (61 +/- 17) years old, P = 0.000]. The numbers of patients were 399, 361, 242 and 413 for 4 respective quarters in order of sequence. (2) And 1030 patients received endoscopy. Among them, there were 897 (87.1%) with upper gastrointestinal hemorrhage and 133 (12.9%) with lower gastrointestinal hemorrhage. Significant differences existed in the mean age of two groups [(51 +/- 20) years old vs (57 +/- 18) years old, P = 0.000]. The male to-female ratio was 656: 241 and 65:68 for these 2 groups respectively (P = 0.000). The percentage of patient with a history of NSAID (non-steroidal anti inflammatory drug) treatment was 22.1% (n = 198) and 12.0% (n = 16) for these 2 groups respectively (P < 0.01). (3) The most common causative diseases of upper gastrointestinal hemorrhage were peptic ulcer (n = 546, 60.8%), esophageal & gastric varices hemorrhage (n = 130, 14.5%) and gastric cancer (n = 40, 4.6%). When the patients were divided into 5 groups of < 12 h, 12-24 h, 24-48 h, 48-72 h and > or = 72 h per time window of gastroscopy, their percentages with endoscopically active hemorrhage were 24.1% (20/83), 14.9% (24/161), 9.6% (16/166), 7.5% (8/106) and 7.6% (29/381) for these groups respectively with statistically significant differences. When peptic ulcer was examined by the Forrest classification, the ratio of grade I a- II c decreased gradually while the ratio of grade III increased gradually among 5 groups (chi2 = 80.414, P = 0.040). (4) The most common causative diseases of lower gastrointestinal hemorrhage were ischemic colitis (n = 44, 33.1%), small intestinal hemorrhage (n = 26, 19.5%) and colonic polyps (n = 18, 13.5%). (5) When the patients were divided into > 65 years old group (n = 277) and < or = 65 years old group (n = 620), the ratio of gastric ulcer and cancer in upper gastrointestinal hemorrhage was higher in the former than in the latter [23.5% (n = 65) vs 8.9% (n = 55) & 9.7% (n = 27) vs 2.1% (n = 13), P < 0.01)]. While the ratio of duodenal ulcer was lower in the former than in the latter [22.4% (n = 62) vs 49.7% (n = 308), P < 0.01]. The ratio of small intestinal hemorrhage in lower gastrointestinal hemorrhage was higher in the former than in the latter (all P < 0.01). CONCLUSION: At the lowest in the third quarter, the incidence rate of acute gastrointestinal hemorrhage is higher in males than that in females at a lower age of onset. More common than lower gastrointestinal hemorrhage, upper gastrointestinal hemorrhage has a lower mean age of onset. Peptic ulcer is the most common disorder in upper gastrointestinal hemorrhage. Ischemic colitis is the most common disorder in lower gastrointestinal hemorrhage. The rate of gastric ulcer and gastric cancer in the old age group is higher than that in the young group. Emergency gastroscopy is recommended. PMID- 22093735 TI - [Microbiological analysis of late infected hip arthroplasty in 62 cases]. AB - OBJECTIVE: To review the type and number of pathogens and their antibiotic sensitivity in patients with late infected total joint replacement so as to offer guidance for the choice of antibiotics. METHODS: A retrospective analysis was conducted for 62 patients whose suspected specimens were obtained intra operatively during a total hip arthroplasty since January 2002 to August 2010 at our department. Their demographic data, bacterial species and antibiotic sensitivity profiles were recorded. RESULTS: Among 62 cases, the cultures were tested positive in 48 cases; the most common bacteria was Gram-positive bacteria (74%). And coagulase-negative staphylococci and Staphylococcus aureus accounted for 62.9% of all bacterial cultures. And the ratio of methicillin-resistant Staphylococcus was 41.18%. CONCLUSION: The late infection of total hip arthroplasty is mainly caused by Gram-positive bacteria. Antibiotic treatment for late periprosthetic infection should be guided by the findings of drug susceptibility. Vancomycin may be used as a primary agent for the treatment of infected hip arthroplasty. PMID- 22093736 TI - [Diagnostic value of 64-slice spiral computed tomographic angiography in vertebral artery stenosis: a meta-analysis]. AB - OBJECTIVE: To evaluate the diagnostic value of 64-slice spiral computed tomographic angiography (CTA) in vertebral artery stenosis through a meta analysis of the relevant data. METHODS: A database search of Cochrane Library, PubMed, EBSCO, CBM-disc and CNKI was performed to identify the relevant English and Chinese language articles with such keywords as 64-slice computer tomography, angiography and vertebral artery stenosis. Quality evaluation, heterogeneity test and sensitivity and specificity to the qualified original data were conducted. Summary receiver operating characteristic (SROC) curve, the area under curve (AUC) and diagnostic odds ratio (DROC) were also calculated. RESULTS: A total of 4 studies were eligible for meta-analysis. Among them, 1 was graded as A and 3 were graded as B. No heterogeneity was found based upon a fixed effect model. For vertebral artery stenosis > or = 50%, the pooled weighted sensitivity, specificity, DROC and SROC AUC was 0.98 (0.94 -1.00), 0.93 (0.89 -0.96), 526.33 and 0.9899 respectively; while for vertebral artery stenosis > or = 50%, the parameters were 0.98 (0.91 - 1.00), 0.97 (0.94 -0.99), 838.40 and 0.9932 respectively. CONCLUSIONS: 64-slice spiral CTA has such a high level of accuracy, sensitivity and specificity in the non-invasive diagnosis of vertebral artery stenosis. PMID- 22093737 TI - [Relationship between proliferation and apoptosis of parathyroid cell in rabbits with primary hyperparathyroidism]. AB - OBJECTIVE: To evaluate the effect of proliferation and apoptosis of parathyroid cell in rabbits with primary hyperparathyroidism (PHPT). METHODS: A total of 80 adult Chinese rabbits were randomly divided into two groups (n = 40 each). The control group was fed with a normal diet (Ca: P, 1:0.7) while the experimental group a high phosphate diet (Ca: P,1:7) for 3-, 4-, 5-, or 6-month intervals to establish the animal model of PHPT. The parathyroid was totally removed for pathological examination after all rabbits were sacrificed. The thyroparathyroid complex was removed en bloc, fixed in neutral formalin and prepared for histological examination. The number of parathyroid cell in PHPT was calculated. Proliferation was determined by immunohistochemistry of proliferation cell nuclear antigen (PCNA) while apoptosis assessed by in situ dUTP biotin nick-end labeling (TUNEL). RESULTS: The number of parathyroid cell was 1.61 times in PHPT than that in the normal control (673 +/- 151, 418 +/- 25, t = - 12.112, P < 0.01). Apoptotic index (AI) increased significantly more in PHPT than that in normal control (200.2 per thousand +/- 125.6 per thousand, 11.0 per thousand +/- 3.0 per thousand, t = -10.193, P < 0.01). The rate of PCNA positive-cell increased significantly more in PHPT than that in control (50.5 per thousand +/- 11.6 per thousand, 26.7 per thousand +/- 2.8 per thousand, t = -13.120, P < 0.05). So did Bcl-2 (460 per thousand +/- 190 per thousand, 67 per thousand +/- 4 per thousand, t = -14. 120, P < 0.05). There was a positive correlation between AI and PCNA (r = 0.861, P < 0.05). It was the same as between AI and Bcl-2 (r = 0.871, P < 0.05). The value of bone mineral density decreased significantly more in PHPT than that in normal control (152 +/- 34, 189 +/- 12, t = 9.236, P < 0.05). CONCLUSION: PHPT may be mainly induced by an excessive proliferation of parathyroid cells and an acceleration of apoptotic process. PMID- 22093738 TI - [Effects of lymphatic drainage and omega-3 polyunsaturated fatty acids on intestinal ischemia-reperfusion injury in rats]. AB - OBJECTIVE: To investigate the effects of lymphatic drainage and omega-3 polyunsaturated fatty acid (omega-3PUFA) on high mobility group box 1 (HMGB1), inflammatory cytokines and endotoxin in rats with intestinal ischemia-reperfusion (I/R) injury. METHODS: A total of 72 SD rats were randomly divided into drainage alone group, I/R group, ischemia-reperfusion plus drainage (I/R + D) group (n = 8 each) and 3 groups with 16 rats undergoing gastrostomy in each group: normal diet (N) group, enteral nutrition (EN) group and enteral nutrition & omega-3PUFA (PUFA) group. And they were further divided into 2 subgroups (n = 8). The rats in I/R and I/R + D groups were subjected to a 60-min ischemia follow by 120-min reperfusion injury of superior mesenteric artery. When the rats suffered I/R injury, intestinal lymph was drained for 180 min in the I/R + D group. The rats in the drainage-alone group received 180-min lymph drainage without I/R injury. After 5 days with different nutrition regimes, the models were established similarly. The rats in the I/R + D sub-groups were treated with intestinal lymph drainage for 180 min. The serum and lymph samples were collected post operatively. Endotoxin was detected by a Limulus kit. The inflammatory cytokines and high mobility group box 1 (HMGB1) were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Endotoxin, inflammatory cytokines and lymphatic HMGB1 of lymphatic in the I/R + D group were higher than those in the drainage-alone group [all P < 0.05, IL-6: (30 +/- 8) pg/ml vs (20 +/- 6) pg/ml, endotoxin: (0.029 +/- 0.011) U/ml vs (0.008 +/- 0.005) U/ml]. The serum levels of endotoxin and inflammatory cytokines in the I/R + D group were lower than those in the I/R group (P < 0.05). The lymphatic levels of TNF-alpha (tumor necrosis factor-alpha) and HMGB1 in the N and EN groups were higher than those in the PUFA group[ TNF-alpha: (46 +/- 17) pg/ml, (54 +/- 16) pg/ml vs (28 +/- 9) pg/ml, HMGB1: (4.8 +/- 1.6) ng/ml, (5.3 +/- 1.8) ng/ml, (3.0 +/- 1.0) ng/ml, all P < 0.05)]. The serum levels of endotoxin, inflammatory cytokines and HMGB1 in the PUFA (I/R) group were lower than those in the N (I/R) group (P < 0.05). The levels of TNF-alpha and HMGB1 were lower in the PUFA (I/R + D) group than those in the N (I/R + D) group (both P < 0.05). CONCLUSION: Lymphatic drainage may reduce the levels of endotoxin, inflammatory cytokines and HMGB1 so as to alleviate the intestinal I/R injury. The intervention of omega-3PUFA has some protective effect through relieving inflammation. PMID- 22093739 TI - [Effects of different cyclic mechanical stretching loads on human tenocytic cytoskeleton in vitro]. AB - OBJECTIVE: To investigate the human tenocyte cytoskeleton under different in vitro stretching conditions and analyze the relations between the changes of tenocytic cytoskeleton and different stretching loads. METHODS: Human tenocytes, cultivated for 5 -7 passages, were stretched under 4%, 8% and 12% cyclic mechanical stretching with a duration of 2, 4, 8, 12, 24 hours and a frequency of 0.5 and 1.0 Hz. Laser scanning confocal microscope was used to examine the changes of F-actin and nucleus after immunofluorescent staining at different cyclic mechanical stretching loads on human tenocyte. The uni-cell average fluorescence intensity was measured with an image analysis system by the photos of human tenocyte cytoskeleton and analyzed by the single factor analysis of variance. RESULTS: After cyclic stretching under 4% stretching with a duration of 2 hours at 0.5 Hz, the microfilament of human tenocyte had an irregular and dim alignment. F-actin was thicker and ruptured under 4% stretching with a duration of 4 hours. Under 8% stretching with a duration of 4 hours at 0.5 Hz, all actin microfilaments ruptured, but part of membrane microfilament remained intact. There was a rising trend of actin filament fracturing under 12% stretching with a duration of 2, 4, 8, 12, 24 hours at 1.0 Hz. And all actin filaments fractured at 24 hours. In the control group, the fluorescent intensity of F-actin was at the highest and the filament remained intact. Under the same stretching frequency, the fluorescent intensity of F-actin had a declining trend and significant differences existed under different stretching loads with different durations (P < 0.05). The fluorescent intensity of F-actin increased in all experimental groups, but it was lower than that of the control group with a duration of 8 hours. The expression of F-actin decreased with a longer duration and reached its lowest at 24 hours. The most obvious phenomenon of nuclear condensation and apoptotic body formation was observed under 4% stretching with a duration of 4 hours at 0.5 Hz. CONCLUSION: Different cyclic mechanical stretching may cause the in vitro breakage and depolymerization of human tenocytic F-actin. Such an effect correlates with stretching force and its duration. PMID- 22093740 TI - [Neuroprotection of a neotype transactivating-brain-derived neurotrophic factor fusion protein with penetrating activity of blood-brain barrier]. AB - OBJECTIVE: To identify the dural activities of neuroprotection and penetrating blood-brain barrier (BBB) for TAT-BDNF (transactivating-brain-derived neurotrophic factor) fusion protein to explore an alternative treatment for the injury of central nerve system (CNS). METHODS: With molecular cloning techniques, a recombinant vector termed pTAT-BDNF was constructed to encode both TAT protein transduction domain and human BDNF. Purified TAT-BDNF fusion protein was generated from Escherichia coli BL21 (DE3). The injury model was established with in vitro cultured cortical neurons of neonatal rats. To observe the neuroprotective effects of TAT-BDNF fusion protein on glutamate-mediated excitotoxic insults, the contents of lactate dehydrogenase (LDH) were measured by spectrophotometry. Immunofluorescence and Hoechst 33342 analyses were used to observe the morphological changes. Immunocytochemical and Nissl stain analysis of TAT-BDNF content in CNS tissue were performed after an intravenous injection of TAT-BDNF fusion protein in normal or spinal cord injured rats. RESULTS: During the study of glutamate-induced excitotoxic insults, as compared with the control group, TAT-BDNF could decrease the apoptotic ratio, reduce the leakage of LDH and enhance the survival of neurons (P < 0.05 ). As demonstrated by immunohistochemistry, TAT-BDNF fusion protein was efficiently delivered into rat brain and spinal cord tissues at 4 h post-injection. At Day 7 post-injury, Nissl stain show that the number and morphology of neurons in the TAT-BDNF group were better than those in the control group. CONCLUSION: The synthetic neotype TAT BDNF possess the dual biological effects of neuroprotection and penetrating BBB. PMID- 22093741 TI - Snoring, mouth-breathing, and apnea trajectories in a population-based cohort followed from infancy to 81 months: a cluster analysis. AB - OBJECTIVE: The objective of this study was to characterize phenotypes of sleep disordered breathing (SDB) in early childhood that clinicians may find useful while monitoring symptom progression and associated SDB morbidity. METHODS: We performed a cluster analysis of SDB's primary symptoms: snoring, mouth-breathing, and apnea. Parents in the Avon Longitudinal Study of Parents and Children (ALSPAC) reported SDB symptoms by questionnaire for their child at 6, 18, 30, 42, 57, 69, and 81 months of age. Participants were those from the original cohort exclusive of children with congental or other medical conditions predisposing growth aberrations or respiratory problems (i.e. cleft palate, heart surgery and associated conditions, genetic syndromes-primarily Down's, cancer or kidney conditions, celiac disease, congenital adrenal hyperplasia), missing SDB measures for >= 2 timepoints, or missing birth length plus 2 subsequent height measures. RESULTS: Five clusters emerged from 10,441 children and were characterized according to patterns of mean severity of SDB symptoms over time. "Normals" (50%) were asymptomatic throughout. The "late snores and mouth-breathing" cluster (20%) remained asymptomatic until 4 years old. The "early snores" (10%) and "early apnea" (10%) clusters had peak symptoms at 6 and 18 months, respectively. In "all SDB after infancy" (10%), symptoms peaked from 30 to 42 months and remained elevated. Exploratory analyses found that "early snores" were significantly shorter than "normals." Associations with tonsillectomies and wheezing frequency supported external validation. CONCLUSIONS: Cluster analysis has elucidated the dynamic multi-symptom expression of SDB. The utility of cluster analysis will be evaluated in future analyses to predict growth, cognition and behavior outcomes. PMID- 22093742 TI - The otolaryngologic manifestations in children with eosinophilic esophagitis. AB - OBJECTIVES: (1) To describe the incidence of eosinophilic esophagitis (EoE) in the population of patients undergoing esophagoscopy with biopsy by a pediatric otolaryngology service. (2) To elucidate the demographics, presenting symptoms, and endoscopic findings in children with EoE. DESIGN: Case series. PATIENTS/METHODS: The reports of esophageal biopsy specimens taken over 5 years in 2429 patients were reviewed. Ninety-two patients who received their initial diagnosis of EoE by the pediatric otolaryngology service with specimens showing 15 or greater eosinophils per high power field (HPF) were included. INTERVENTIONS: The demographic data, history, presenting symptoms, and endoscopic findings were reviewed retrospectively for the patients. MAIN OUTCOME MEASURE: The percentage of children diagnosed with EoE of all children undergoing esophageal biopsy. RESULTS: A total of 92 children were diagnosed with EoE (3.8% of total children biopsied). The mean age at biopsy was 4.4 years, much lower than previously reported in the literature (approximately 8 years); 73% were boys and 27% girls. The main presenting symptom was cough (46%) followed by hoarseness, throat clearing, burping/vomiting, and abdominal pain. Forty three percent had a history of asthma and 17% a history of GERD. Half of patients had esophageal edema, a third were normal, and only a quarter had mucosal furrowing on endoscopic examination. CONCLUSIONS: EoE is increasingly diagnosed as a clinical entity with a distinct symptom profile and etiology. Increased understanding of EoE and its predisposing factors requires a multidisciplinary approach to diagnosis and management involving the pediatric otolaryngologist. PMID- 22093743 TI - Novel mutations in ATP6V0A4 are associated with atypical progressive sensorineural hearing loss in a Chinese patient with distal renal tubular acidosis. AB - Mutations in ATP6V0A4 lead to distal renal acidosis (MIM 602722) with a highly variable range of hearing phenotype. We identified two novel ATP6V0A4 mutations in a Chinese patient with distal renal tubular acidosis and late onset hearing loss, and presented the first direct evidence of progressive hearing loss associated with ATP6V0A4 mutations by sequential audiological assessments. A unique audiometric profile of progressive hearing loss of the patient was described that may provide useful insights when studying the highly variable hearing phenotypes associated with the ATP6V0A4 mutations. PMID- 22093744 TI - Pathological stage distribution in patients treated with radical prostatectomy reflecting the need for protocol-based active surveillance: results from a contemporary European patient cohort. AB - Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? Low-risk prostate cancer is frequently diagnosed in the context of PSA screening or during a routine check-up. For those patients, to avoid possible overtreatment AS is an increasingly chosen treatment option. However, the concept of AS could possibly misclassify potentially dangerous PCa as a low-risk disease resulting in inferior cancer control outcomes. In the present study, we could demonstrate that the histopathological results of patients treated by RP in course of AS are significantly better if the selection criteria for AS are entirely fulfilled. Our findings underline the importance of a strict and precise admittance procedure for patients with early prostate cancer who are willing to undergo an AS programme. OBJECTIVE: * To compare the histopathological outcomes of patients treated with radical prostatectomy (RP) after an initial active surveillance (AS) for localized, low risk prostate cancers (PCa) among men who fulfilled the Epstein criteria at diagnosis with those who did not. PATIENTS AND METHODS: * In all, 283 patients with localized PCa were initially managed at our institution with AS. * In all, ~ 50% originated from the European Randomized Study of Screening for Prostate Cancer (ERSPC) participants from Switzerland: 75 (26.5%) patients underwent treatment during follow-up and 61 were treated with RP (21.6%). * These patients were stratified into those who did (n= 39) vs those who did not (n= 22) entirely fulfil AS inclusion criteria according to Epstein et al. at PCa diagnosis. RESULTS: * Patients who did completely fulfil the AS inclusion criteria had significantly lower prostate-specific antigen (PSA)-values (4.9 vs 7.8 ng/mL; P= 0.02), a significantly lower PSA density at diagnosis (0.09 vs 0.2 ng/mL/ccm; P= 0.007) and at RP, a higher proportion of organ-confined cancers (89.7% vs 59.1%, P= 0.02) and fewer positive surgical margins (25.6% vs 40.9%). * However, the rate of favourable histopathological outcome, defined as organ-confined disease with negative surgical margins, was statistically significantly higher in the group fulfilling AS criteria (69.2% vs 40.9%; P= 0.03). CONCLUSIONS: * In our AS series, 26.5% of the patients underwent definitive therapy. * Most patients treated with RP had organ-confined disease in the majority of cases, especially when the Epstein criteria were rigorously fulfilled at PCa diagnosis. * This underlines the importance of a strict and precise per protocol AS for patients with early PCa, otherwise there is a risk of missing more significant disease. PMID- 22093745 TI - Cellular responses of Saccharomyces cerevisiae at near-zero growth rates: transcriptome analysis of anaerobic retentostat cultures. AB - Extremely low specific growth rates (below 0.01 h(-1) ) represent a largely unexplored area of microbial physiology. In this study, anaerobic, glucose limited retentostats were used to analyse physiological and genome-wide transcriptional responses of Saccharomyces cerevisiae to cultivation at near-zero specific growth rates. While quiescence is typically investigated as a result of carbon starvation, cells in retentostat are fed by small, but continuous carbon and energy supply. Yeast cells cultivated near-zero specific growth rates, while metabolically active, exhibited characteristics previously associated with quiescence, including accumulation of storage polymers and an increased expression of genes involved in exit from the cell cycle into G(0) . Unexpectedly, analysis of transcriptome data from retentostat and chemostat cultures showed, as specific growth rate was decreased, that quiescence-related transcriptional responses were already set in at specific growth rates above 0.025 h(-1) . These observations stress the need for systematic dissection of physiological responses to slow growth, quiescence, ageing and starvation and indicate that controlled cultivation systems such as retentostats can contribute to this goal. Furthermore, cells in retentostat do not (or hardly) divide while remaining metabolically active, which emulates the physiological status of metazoan post-mitotic cells. We propose retentostat as a powerful cultivation tool to investigate chronological ageing-related processes. PMID- 22093746 TI - Functional characterization of the regulators of calcineurin in Candida glabrata. AB - The serine-threonine-specific protein phosphatase calcineurin is a key mediator of various stress responses in fungi. Herein, we characterized functions of the endogenous regulators of calcineurin (RCNs), Rcn1 and Rcn2, in the pathogenic fungus Candida glabrata. Rcn1 exerted both inhibitory and stimulatory effects on calcineurin signaling, but Rcn2 displayed only inhibitory activity. Phenotypic analyses of C. glabrata strains lacking either RCNs, calcineurin, or both revealed that calcineurin requires Rcn1, but not Rcn2, for antifungal tolerance in C. glabrata. PMID- 22093748 TI - Alcohol-based quorum sensing plays a role in adhesion and sliding motility of the yeast Debaryomyces hansenii. AB - The yeast Debaryomyces hansenii was investigated for its production of alcohol based quorum sensing (QS) molecules including the aromatic alcohols phenylethanol, tyrosol, tryptophol and the aliphatic alcohol farnesol. Debaryomyces hansenii produced phenylethanol and tyrosol, which were primarily detected from the end of exponential phase indicating that they are potential QS molecules in D. hansenii as previously shown for other yeast species. Yields of phenylethanol and tyrosol produced by D. hansenii were, however, lower than those produced by Candida albicans and Saccharomyces cerevisiae and varied with growth conditions such as the availability of aromatic amino acids, ammonium sulphate, NaCl, pH and temperature. Tryptophol was only produced in the presence of tryptophane, whereas farnesol in general was not detectable. Especially, the type strain of D. hansenii (CBS767) had good adhesion and sliding motility abilities, which seemed to be related to a higher hydrophobicity of the cell surface of D. hansenii (CBS767) rather than the ability to form pseudomycelium. Addition of phenylethanol, tyrosol, tryptophol and farnesol was found to influence both adhesion and sliding motility of D. hansenii. PMID- 22093747 TI - Subcellular distribution of glutathione and its dynamic changes under oxidative stress in the yeast Saccharomyces cerevisiae. AB - Glutathione is an important antioxidant in most prokaryotes and eukaryotes. It detoxifies reactive oxygen species and is also involved in the modulation of gene expression, in redox signaling, and in the regulation of enzymatic activities. In this study, the subcellular distribution of glutathione was studied in Saccharomyces cerevisiae by quantitative immunoelectron microscopy. Highest glutathione contents were detected in mitochondria and subsequently in the cytosol, nuclei, cell walls, and vacuoles. The induction of oxidative stress by hydrogen peroxide (H(2) O(2) ) led to changes in glutathione-specific labeling. Three cell types were identified. Cell types I and II contained more glutathione than control cells. Cell type II differed from cell type I in showing a decrease in glutathione-specific labeling solely in mitochondria. Cell type III contained much less glutathione contents than the control and showed the strongest decrease in mitochondria, suggesting that high and stable levels of glutathione in mitochondria are important for the protection and survival of the cells during oxidative stress. Additionally, large amounts of glutathione were relocated and stored in vacuoles in cell type III, suggesting the importance of the sequestration of glutathione in vacuoles under oxidative stress. PMID- 22093749 TI - Versatile use of Schizosaccharomyces pombe plasmids in Saccharomyces cerevisiae. AB - The two model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe appear to have diverged 1000 million years ago. Here, we describe that S. pombe vectors can be propagated efficiently in S. cerevisiae as pUR19 derivatives, and the pREP and pJR vector series carrying the S. cerevisiae LEU2 or the S. pombe ura4(+) selection marker are maintained in S. cerevisiae cells. In addition, genes transcribed from the S. pombe nmt1(+) promoter and derivatives are expressed in budding yeast. Thus, S. pombe vectors can be used as shuttle vectors in S. cerevisiae and S. pombe. Our finding greatly facilitates the testing for functional orthologs of protein families and simplifies the cloning of new S. pombe plasmids by using the highly efficient in vivo homologous recombination activity of S. cerevisiae. PMID- 22093750 TI - Pkc1 and actin polymerisation activities play a role in ribosomal gene repression associated with secretion impairment caused by oxidative stress. AB - In Saccharomyces cerevisiae, the cell integrity pathway plays a role in the oxidative stress response. In this study, we show that the Pkc1 protein mediates oxidative signalling by helping to downregulate ribosomal gene expression when cells are exposed to hydrogen peroxide. An active actin cytoskeleton is required for this function, because the cells blocked in actin polymerisation were unable to repress ribosomal gene transcription. Following the invertase secretion pattern, we hypothesize that oxidative stress induced by hydrogen peroxide could have affected the latter steps of secretion. This would explain why the Pkc1 function was required to repress ribosomal biogenesis. PMID- 22093751 TI - Large outbreak of verocytotoxin-producing Escherichia coli O157 infection in visitors to a petting farm in South East England, 2009. AB - In the summer of 2009, an outbreak of verocytotoxigenic Escherichia coli O157 (VTEC O157) was identified in visitors to a large petting farm in South East England. The peak attack rate was 6/1000 visitors, and highest in those aged <2 years (16/1000). We conducted a case-control study with associated microbiological investigations, on human, animal and environmental samples. We identified 93 cases; 65 primary, 13 secondary and 15 asymptomatic. Cases were more likely to have visited a specific barn, stayed for prolonged periods and be infrequent farm visitors. The causative organism was identified as VTEC O157 PT21/28 with the same VNTR profile as that isolated in faecal specimens from farm animals and the physical environment, mostly in the same barn. Contact with farm livestock, especially ruminants, should be urgently reviewed at the earliest suspicion of a farm-related VTEC O157 outbreak and appropriate risk management procedures implemented without delay. PMID- 22093752 TI - Formation and characterization of pDNA-loaded alginate microspheres for oral administration in mice. AB - Alginate, a natural polysaccharide, was explored in this study as an oral delivery vehicle of a mammalian expression vector into the murine intestinal mucosa. Alginate microspheres were produced through water-in-oil (W/O) emulsification method. Average diameter sizes of microspheres were 46.88 MUm+/ 3.07 MUm with significant size reduction upon utilization of 1.0% Span80. Plasmid DNA (pDNA) carrying green fluorescent protein reporter gene (GFP), pVAX-GFP, was encapsulated within microspheres at efficiencies of 72.9 to 74.4%, carrying maximum load of 6 MUg pDNA. Alginate microspheres demonstrated shrinkage in pH 1.2 and swelling in pH 9.0 with pDNA release about twice the amount released in acidic environment. Oral delivery of pVAX-GFP loaded-microspheres, at 50 MUg, 100 MUg and 150 MUg dose, was performed on BALB/c mice. Tissue biodistribution, investigated through flow cytometric analysis, demonstrated GFP positive intestinal cells (<1.0%) with 1.3-fold higher levels for the 100 MUg dose; therefore suggesting feasibility of the approach for oral gene delivery and vaccination. PMID- 22093753 TI - Neuroprotective activity of galloylated cyanogenic glucosides and hydrolysable tannins isolated from leaves of Phyllagathis rotundifolia. AB - The galloylated cyanogenic glucosides based on prunasin (1-7), gallotannins (8 14), ellagitannins (15-17), ellagic acid derivatives (18, 19) and gallic acid (20) isolated from the leaves of Phyllagathis rotundifolia (Melastomataceae) were investigated for their neuroprotective activity against hydrogen peroxide (H(2)O(2))-induced oxidative damage in NG108-15 hybridoma cell line. Among these compounds, the gallotannins and ellagitannins exhibited remarkable neuroprotective activities against oxidative damage in vitro as compared to galloylated cyanogenic glucosides and ellagic acid derivatives in a dose dependent manner. They could be explored further as potential natural neuroprotectors in various remedies of neurodegenerative diseases. PMID- 22093754 TI - Rapid in vivo analysis of synthetic promoters for plant pathogen phytosensing. AB - BACKGROUND: We aimed to engineer transgenic plants for the purpose of early detection of plant pathogen infection, which was accomplished by employing synthetic pathogen inducible promoters fused to reporter genes for altered phenotypes in response to the pathogen infection. Toward this end, a number of synthetic promoters consisting of inducible regulatory elements fused to a red fluorescent protein (RFP) reporter were constructed for use in phytosensing. RESULTS: For rapid analysis, an Agrobacterium-mediated transient expression assay was evaluated, then utilized to assess the inducibility of each synthetic promoter construct in vivo. Tobacco (Nicotiana tabacum cv. Xanthi) leaves were infiltrated with Agrobacterium harboring the individual synthetic promoter reporter constructs. The infiltrated tobacco leaves were re-infiltrated with biotic (bacterial pathogens) or abiotic (plant defense signal molecules salicylic acid, ethylene and methyl jasmonate) agents 24 and 48 hours after initial agroinfiltration, followed by RFP measurements at relevant time points after treatment. These analyses indicated that the synthetic promoter constructs were capable of conferring the inducibility of the RFP reporter in response to appropriate phytohormones and bacterial pathogens, accordingly. CONCLUSIONS: These observations demonstrate that the Agrobacterium-mediated transient expression is an efficient method for in vivo assays of promoter constructs in less than one week. Our results provide the opportunity to gain further insights into the versatility of the expression system as a potential tool for high throughput in planta expression screening prior to generating stably transgenic plants for pathogen phytosensing. This system could also be utilized for temporary phytosensing; e.g., not requiring stably transgenic plants. PMID- 22093755 TI - Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss. AB - Long-term outcomes following renal transplantation remain disappointing. Recently, interest has focused on the antibody-mediated component of allograft injury and the deleterious effects of DSA. We applied a novel C1q solid-phase assay in parallel with the standard IgG SAB assay to identify DSA with the potential to activate complement by binding C1q. Among 193 consecutive renal transplants at our center, 19.2% developed de novo DSA following transplantation. Of the patients with DSA, 43% had antibodies that bound C1q in vitro [C1q+ DSA]. Patients with C1q+ DSA were more likely to develop allograft loss than patients with DSA that did not bind C1q (46.7% vs. 15%; p = 0.04); patients with C1q+ DSA were nearly six times more likely to lose their transplant than those with C1q- DSA. Additionally, patients with C1q+ DSA who underwent allograft biopsy were more likely to demonstrate C4d deposition (50% vs. 8%; p = 0.03) and meet criteria for acute rejection (60% vs. 17%; p = 0.02) when compared with patients with DSA that did not bind C1q. These data suggest that DSA with the ability to activate complement, as determined by this novel C1q assay, are associated with greater risk of acute rejection and allograft loss. PMID- 22093756 TI - Perceived nursing service quality in a tertiary care hospital, Maldives. AB - The present study explored nurses' and patients' expectations of nursing service quality, their perception of performance of nursing service quality performed by nurses, and compared nursing service quality, as perceived by nurses and patients. The sample consisted of 162 nurses and 383 patients from 11 inpatient wards/units in a tertiary care hospital in the Maldives. Data were collected using the Service Quality scale, and analyzed using descriptive statistics and the Mann-Whitney U-test. The results indicated that the highest expected dimension and perceived dimension for nursing service quality was Reliability. The Responsiveness dimension was the least expected dimension and the lowest performing dimension for nursing service quality as perceived by nurses and patients. There was a statistically significant difference between nursing service quality perceived by nurses and patients. The study results could be used by nurse administrators to develop strategies for improving nursing service quality so that nursing service delivery process can be formulated in such a way as to reduce differences of perception between nurses and patients regarding nursing service quality. PMID- 22093757 TI - The effect of ionized species on microsomal binding. AB - The effect of neutral molecules on microsomal binding is known through studies by Austin and co-workers, but the effect of ionised species has hitherto not been elucidated. The present work sets out to determine the role of ionised species on microsomal binding. Data on microsomal binding obtained by Austin and co-workers have been analyzed by the method of Abraham and Acree that includes descriptors for neutral molecules, protonated base cations and carboxylate anions. An LFER has been obtained that includes neutral molecules, cations and anions in the same equation. It is shown that carboxylic acid anions bind to microsomes about 18 times less than the corresponding neutral carboxylic acids, but that protonated bases bind as strongly as the corresponding neutral bases. We interpret the stronger binding than expected of protonated bases as due to interaction with the phosphate groups on the phospholipids in the microsomes. Comparison with partition into a cerasome membrane suggests that this interaction corresponds to about a ten to twenty-fold increase in binding to microsomes. PMID- 22093758 TI - Synthesis and biological activity of dihydroimidazole and 3,4 dihydrobenzo[4,5]imidazo[1,2-a][1,3,5]triazins. AB - Reaction of 2-guanidinobenzimidazole with halogenated active methylenes and ketones gave dihydroimidazole and 3,4-dihydrobenzo[4,5]imidazo [1,2 a][1,3,5]triazin derivatives in very good yield. The anti-bacterial evaluation of the newly synthesized products against broad spectrum of bacteria was performed. Most of products showed high inhibitory effect. All compounds have been characterized based on IR, (1)H NMR, (13)C NMR and Mass spectra. PMID- 22093759 TI - Induction of cell cycle arrest by the carbazole alkaloid Clauszoline-I from Clausena vestita D. D. Tao via inhibition of the PKCdelta phosphorylation. AB - Sixteen carbazole alkaloids from Clausena vestita D. D. Tao were extracted, and their anti-tumor activities were evaluated. Among the extracts, Clauszoline-I exhibited an obvious growth inhibitory activity against several cancer cell lines through its ability to induce cell cycle arrest in the S and G2/M phases. A dramatic morphologic change with decreased F-actin staining and RhoA activity was found in Clauszoline-I treated HepG2 cells, in which the phosphorylation of PKCdelta (Ser643) was inhibited. Our results indicated that induction cell cycle arrest by Clauszoline-I might be achieved by decreasing the RhoA activity via the inhibition of PKCdelta phosphorylation. PMID- 22093760 TI - Synthesis of osteotropic hydroxybisphosphonate derivatives of fluoroquinolone antibacterials. AB - 1-Hydroxybisphosphonate derivatives of ciprofloxacin, gatifloxacin and moxifloxacin have been synthesized using Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction. The 1,2,3-triazol linked hydroxybisphosphonate derivative of ciprofloxacin exhibited antibacterial activity comparable to the parent antibiotic and all fluoroquinolone-bisphosphonates displayed osteotropic properties in a bone model. PMID- 22093761 TI - Synthesis and antitumor activity of conjugates of 5-Fluorouracil and emodin. AB - A series of conjugates of 5-Fluorouracil (5-FU) and emodin were synthesized by coupling trimethyl emodin with N(1), N(3) dialkylated 5-FU. The 5-FU moiety contained various substituents at the N(3)-position were linked to the 2-position of trimethyl emodin via a methylene linkage. Their cytotoxicity against three cancer cell lines and one noncancerous cell were studied. The results revealed that some of conjugates exhibited better or comparable in vitro antitumor activity to 5-FU and emodin and low toxicity in the normal cell. The structure activity relationship study showed N(3)-aromatic substituent was important for their cytotoxic activity. PMID- 22093762 TI - Evolutionary maintenance of filovirus-like genes in bat genomes. AB - BACKGROUND: Little is known of the biological significance and evolutionary maintenance of integrated non-retroviral RNA virus genes in eukaryotic host genomes. Here, we isolated novel filovirus-like genes from bat genomes and tested for evolutionary maintenance. We also estimated the age of filovirus VP35-like gene integrations and tested the phylogenetic hypotheses that there is a eutherian mammal clade and a marsupial/ebolavirus/Marburgvirus dichotomy for filoviruses. RESULTS: We detected homologous copies of VP35-like and NP-like gene integrations in both Old World and New World species of Myotis (bats). We also detected previously unknown VP35-like genes in rodents that are positionally homologous. Comprehensive phylogenetic estimates for filovirus NP-like and VP35 like loci support two main clades with a marsupial and a rodent grouping within the ebolavirus/Lloviu virus/Marburgvirus clade. The concordance of VP35-like, NP like and mitochondrial gene trees with the expected species tree supports the notion that the copies we examined are orthologs that predate the global spread and radiation of the genus Myotis. Parametric simulations were consistent with selective maintenance for the open reading frame (ORF) of VP35-like genes in Myotis. The ORF of the filovirus-like VP35 gene has been maintained in bat genomes for an estimated 13. 4 MY. ORFs were disrupted for the NP-like genes in Myotis. Likelihood ratio tests revealed that a model that accommodates positive selection is a significantly better fit to the data than a model that does not allow for positive selection for VP35-like sequences. Moreover, site-by-site analysis of selection using two methods indicated at least 25 sites in the VP35 like alignment are under positive selection in Myotis. CONCLUSIONS: Our results indicate that filovirus-like elements have significance beyond genomic imprints of prior infection. That is, there appears to be, or have been, functionally maintained copies of such genes in mammals. "Living fossils" of filoviruses appear to be selectively maintained in a diverse mammalian genus (Myotis). PMID- 22093763 TI - Adult urologic sarcoma: experience during 2 decades. AB - OBJECTIVE: To identify factors associated with long-term outcome and to report possibly meaningful clinical features in a unicentric sample of adult urologic sarcomas. MATERIALS AND METHODS: Thirty-five patients treated between 1992 and 2011 were studied. Except for 3 patients, surgery was the initial treatment. The median follow-up in the surviving (censored) patients was 11.3 years. Kaplan Meier method and competing risk analysis were used to evaluate outcome. Disease recurrence, disease-specific mortality, and overall mortality were the study endpoints. Comparisons were made with the log rank and the Pepe-Mori tests. Cox proportional hazard models were used to identify independent predictors of disease recurrence. RESULTS: Only disease grade was significantly associated with all 3 study endpoints. The primary tumor site was significantly associated with disease-specific and recurrence-free survival but did not reach the significance level concerning overall survival. In the multivariate analysis, primary site and tumor grade were identified as predictors of disease recurrence. Whereas 10-year disease-specific survival was 100% in patients with low grade inguinoscrotal tumors, it was 0% in patients with high grade disease arising from other sites. CONCLUSIONS: Low grade and inguinoscrotal origin are factors associated with favorable outcome in urologic sarcomas. Repeat interventions to remove or to inactivate recurrent tumors or metastases seem to provide clinical benefit in individual cases. PMID- 22093764 TI - Adolescent threat-related interpretive bias and its modification: the moderating role of regulatory control. AB - Dual process models describe psychopathology as the consequence of an imbalance between a fast, impulsive system and a regulatory control system and have recently been applied to anxiety disorders. The aim of the current study was to specifically examine the role of a regulatory control system in regulating 1) threat-related interpretive bias and 2) the effectiveness of interpretive bias training in adolescents. In total, 67 adolescents participated and followed either a positive Cognitive Bias Modification of Interpretation (CBM-I) training or a placebo-control condition. Results revealed that interpretive bias and the effectiveness of its modification depended on individual differences in regulatory control. That is, low levels of regulatory control in combination with high levels of state anxiety were associated with the strongest threat-related interpretive bias and those individuals benefited the most of the positive interpretation training. The current study provided empirical support for the role of dual processes in adolescent threat-related interpretive bias. PMID- 22093765 TI - Repeatable target localization for long-term in vivo imaging of mice with 2 photon microscopy. AB - Repetitive in vivo imaging in mice has become an indispensable tool for studying dynamic changes in structure and function of the brain. We describe a head fixation system, which allows rapid re-localization of previously imaged regions of interest (ROIs) within the brain. Such ROIs can be automatically relocated and imaged over weeks to months with negligible rotational change and only minor translational errors. Previously stored imaging positions can be fully automated re-localized within a few seconds. This automated rapid and accurate relocation simplifies image acquisition and post-processing in longitudinal imaging experiments. Moreover, as the laser is only used for data acquisition and not for finding previously imaged ROIs, the risk of laser induced tissue damage and photobleaching is greatly reduced. Thus, here described head fixation device appears well suited for in vivo repetitive long-term imaging in rodent brain. PMID- 22093766 TI - [An update on focal infection of oral origin]. AB - Focal infection of oral origin means that an oral infectious focus may have widespread effects. This concept remains controversial since it is difficult to prove the oral origin of germs responsible for an extra-oral infection. Experiments on animal models and clinical studies suggested several physiopathological mechanisms: bacteremia, toxinic and immunological mechanisms. Various operations induce the passage of bacterial flora (transcytosis) and its toxins into the bloodstream: oral care, chewing, or tooth brushing. Bacteremia is worsened by poor oral hygiene or an infection. The germs are usually destroyed by the host's reticuloendothelial system in a few minutes, but the presence of a valvular disease or a weak immune system favors focal infection. Besides infectious endocarditis, this may concern cardiovascular diseases, lung infections, prematurity and hypotrophy, diabetes, prosthetic infections, cerebral abscesses, etc. This update is based on literature review, selected according to its high level of scientific proof, as well as on a selected choice of consensus conferences. The current recommendation is to limit antibiotic prophylaxis to the high bacteremia risk procedures and to patients highly at risk of developing a focal infection. PMID- 22093767 TI - The consequences of tinnitus in long-standing Meniere's disease. AB - OBJECTIVE: To explore the perceived consequences of tinnitus in patients with long-standing Meniere's disease (MD). METHOD: A questionnaire-based cross sectional investigation of 183 randomly selected members of the Finnish Meniere's Federation. It assessed general health related quality of life (EQ-5D), a participation restriction scale, self-listed consequences and a rating of effects of MD on life. RESULTS: When the effects of the other cardinal symptoms of Meniere's disease were partialled out, the main reported impacts of tinnitus related to anxiety, sleep and depression. It also contributed to some difficult listening situations and to interactions with significant others. Tinnitus explained a significant component of disease-specific quality of life (QoL), but did not relate significantly to the generic measures used. However, the measure 'mood' in the QoL scale was significantly associated with severe tinnitus. CONCLUSION: The most important specific impacts of tinnitus in chronic Meniere's disease relate to broadly psychological factors and mood. PMID- 22093768 TI - A CMOS label-free DNA sensor using electrostatic induction of molecular charges. AB - This paper reports a label-free biosensor for the detection of DNA hybridization. The proposed biosensor measures the surface potential on oligonucleotide modified electrodes using a direct charge accumulation method. The sensor directly and repeatedly measures the charges induced in the working electrode, which correspond to intrinsic negative charges in immobilized molecules. The sensor achieves an improved signal-to-noise ratio (SNR), through the oversampling effect of accumulation for charges and the differential architecture. The sensor also shows stable, robust, and reproducible measurement independent of slight changes in the reference voltage, unlike previous ion-sensitive field effect transistors (ISFETs), providing the benefits of choosing a wide variety of reference electrode materials. The proposed device is integrated with working electrodes, a reference electrode and readout circuits into one package via a 0.35 MUm complementary metal-oxide-semiconductor (CMOS) process. The sensor achieves a detectable range of 88.3 dB and a detection limit of 36 MUV for surface potential. It is demonstrated that the sensor successfully achieves specific detection of oligonucleotide sequences derived from the H5N1 avian influenza virus. The experiments show a limit of detection of 100 pM and include a single base mismatch test in 18-mer oligonucleotides. PMID- 22093769 TI - Mechanical force-based probing of intracellular proteins from living cells using antibody-immobilized nanoneedles. AB - We developed a method combining atomic force microscopy (AFM) and antibody immobilized nanoneedles to discriminate living cells by probing intracellular cytoskeletal proteins without the need for cell labeling. The nanoneedles are ultra-thin AFM probes sharpened to 200 nm in diameter. While retracting a nanoneedle inserted into a cell, we measured the mechanical force needed to unbind the antibody-target protein complex. Using this method, the intermediate filament protein, nestin and neurofilament were successfully detected in mouse embryonic carcinoma P19 cells and rat primary hippocampal cells within a minute for a single cell and cell differentiation states could be determined. Additionally, the measured magnitude of the force detecting nestin was indicative of the malignancy of breast cancer cells. This method was shown to affect neither the doubling time of cells nor does it leave extrinsic antibodies within the examined cells, allowing to be used in subsequent analyses in their native state. PMID- 22093770 TI - Development of a multilayered polymeric DNA biosensor using radio frequency technology with gold and magnetic nanoparticles. AB - This study utilized the radio frequency (RF) technology to develop a multilayered polymeric DNA sensor with the help of gold and magnetic nanoparticles. The flexible polymeric materials, poly (p-xylylene) (Parylene) and polyethylene naphtholate (PEN), were used as substrates to replace the conventional rigid substrates such as glass and silicon wafers. The multilayered polymeric RF biosensor, including the two polymer layers and two copper transmission structure layers, was developed to reduce the total sensor size and further enhance the sensitivity of the biochip in the RF DNA detection. Thioglycolic acid (TGA) was used on the surface of the proposed biochip to form a thiolate-modified sensing surface for DNA hybridization. Gold nanoparticles (AuNPs) and magnetic nanoparticles (MNPs) were used to immobilize on the surface of the biosensor to enhance overall detection sensitivity. In addition to gold nanoparticles, the magnetic nanoparticles has been demonstrated the applicability for RF DNA detection. The performance of the proposed biosensor was evaluated by the shift of the center frequency of the RF biosensor because the electromagnetic characteristic of the biosensors can be altered by the immobilized multilayer nanoparticles on the biosensor. The experimental results show that the detection limit of the DNA concentration can reach as low as 10 pM, and the largest shift of the center frequency with triple-layer AuNPs and MNPs can approach 0.9 and 0.7 GHz, respectively. Such the achievement implies that the developed biosensor can offer an alternative inexpensive, disposable, and highly sensitive option for application in biomedicine diagnostic systems because the price and size of each biochip can be effectively reduced by using fully polymeric materials and multilayer-detecting structures. PMID- 22093771 TI - Ultrasensitive and dual functional colorimetric sensors for mercury (II) ions and hydrogen peroxide based on catalytic reduction property of silver nanoparticles. AB - The method provides an innovative dual functional sensors for mercury (II) ions and hydrogen peroxide. The addition of H(2)O(2) to the mixture of silver nanoparticles (AgNPs) and Hg(2+) induced color changes of the solution within several seconds even at 2.0 nM Hg(2+). Other metallic ions could not induce color change even at 10 MUM. Of importance, this probe was not only successfully applied to detect Hg(2+), but also it could be used to sense H(2)O(2) at a concentration as low as 50 nM (by naked-eye). The outstanding sensitivity and selectivity property for Hg(2+) and H(2)O(2) resulted from the AgNPs mediated reduction of Hg(2+) to elementary Hg in the presence of H(2)O(2), causing the aggregation and colorimetric response of AgNPs. This sensitive and selective colorimetric assay opens up a fresh insight of development facile and fast detection methods for metal ions and biomolecules using the special catalytic reactivity of AgNPs. PMID- 22093772 TI - Stabilization and modulation of the phycobilisome by calcium in the calciphilic freshwater red alga Bangia atropurpurea. AB - The bangiophycean filamentous red alga Bangia atropurpurea is distributed in freshwater habitats such as littoral and splash zones of lakes or rapid currents distant from the sea. In these habitats, the distribution and growth of this alga appear to be related to hard water rich in calcium ions. To characterize the eco physiological properties of this calciphilic red alga, we examined the effects of long-term and short-term Ca(2+) depletion on photosynthetic growth of the thallus and on the phycobilisome. Long-term culture experiments suggested that higher Ca(2+) concentrations (>50mgL(-1)) were required to sustain thallus growth and pigmentation of cells. In short-term Ca(2+)-depletion treatments, fluorescence derived from phycoerythrin (PE) fluctuated, although the absorption spectra of the thalli did not change. After 30 min of Ca(2+) depletion, the fluorescence lifetime of PE became markedly longer, indicating that the energy transfer from PE to phycocyanin (PC) was suppressed. The fluorescence lifetime of PE returned to its original value within a short time after 4h of Ca(2+) depletion, however, energy transfer from PE to PC was still suppressed. This suggested that the excitation energy absorbed by PE was quenched during prolonged Ca(2+) depletion. The efficient energy transfer from PC and allophycocyanin were unchanged during these treatments. PMID- 22093773 TI - Disseminated Mycobacterium marinum infection in a hematopoietic stem cell transplant recipient. AB - Mycobacterium marinum is a photochromogenic mycobacterium that is ubiquitous in the aquatic environment. In the general population, exposure to aquaria is the most common cause of M. marinum infection. Known as "swimmer's granuloma" or "fish tank granuloma," M. marinum is an occupational hazard for aquarium cleaners and fishermen. There are several reports in the literature of M. marinum infection in immunocompromised hosts, including those with solid organ transplants, but none in patients who have received stem cell transplants (SCTs). To our knowledge, this is a first report of disseminated M. marinum infection in an SCT recipient who continued to develop new skin lesions even after months of targeted therapy. The implications are that elderly patients who receive T-cell depleted SCTs may be at prolonged risk for pathogens dependent on cellular immunity, and the presentation of illness with such pathogens may be more severe and widely disseminated than might otherwise be expected. PMID- 22093774 TI - Molecular characterization of China rabies virus vaccine strain. AB - BACKGROUND: Rabies virus (RV), the agent of rabies, can cause a severe encephalomyelitis in several species of mammals, including humans. As a human rabies vaccine strain employed in China, the genetic knowledge of the aG strain has not been fully studied. The main goal of the present study is to amplify the whole genome of aG strain, and genetic relationships between other vaccine strains and wild strains were analyzed. RESULTS: The entire genome of human rabies virus vaccine strain aG employed in China was sequenced; this is the second rabies virus vaccine strain from China to be fully characterized. The overall organization and the length of the genome were similar to that of other lyssaviruses. The length of aG strain was 11925nt, comprising a leader sequence of 58nt, nucleoprotein (N) gene of 1353nt, phosphoprotein (P) gene of 894 nt, matrix protein (M) gene of 609nt, glycoprotein (G) gene of 1575nt, RNA-dependent RNA polymerase (RdRp,L) gene of 6384nt, and a trailer region of 70 nt. There was TGAAAAAAA (TGA7) consensus sequence in the end of each gene, except AGA7 at the end of G gene. There was AACAYYYCT consensus start signal at the beginning of each gene. CONCLUSIONS: In this report, we analyzed the full genome of China human rabies vaccine strain aG. Our studies indicated that the genome of aG retained the basic characteristics of RV. At gene level, N was the most conserved among the five coding genes, indicating this gene is the most appropriate for quantitative genotype definition. The phylogenetic analysis of the N indicated the aG strain clustered most closely with Japanese and Russian rabies vaccine strains, suggesting that they may share the same ancestor; also, the aG strain did not share high homology with wild strains isolated from China, making it may not be the best vaccine strain, more research is needed to elucidate the genetic relationship among the RV circulating in China. PMID- 22093775 TI - New treatment paradigm for prostate cancer: abarelix initiation therapy for immediate testosterone suppression followed by a luteinizing hormone-releasing hormone agonist. AB - Study Type - Therapy (prospective cohort). Level of Evidence 2a. What's known on the subject? and What does the study add? The sequential administration of a GnRH antagonist followed by an LHRH agonist in the management of prostate cancer patients has not been studied, but such a program would provide a more physiologic method of achieving testosterone suppression and avoid the obligatory testosterone surge and need for concomitant antiandrogens that accompany LHRH agonist therapy. The current study which uses abarelix initiation therapy for 12 weeks followed by either leuprolide or goserelin demonstrates the ability to more rapidly achieve testosterone suppression, avoid the obligatory LHRH induced testosterone surge, avoid the necessity of antiandrogens, all of which were accomplished safely, without inducing either additional or novel safety issues. OBJECTIVE: * To demonstrate the safety and endocrinological and biochemical efficacy of initiating treatment with the gonadotropin-releasing hormone (GnRH) antagonist, abarelix, followed by administration of an luteinizing hormone releasing hormone (LHRH) agonist in patients with advanced and metastatic prostate cancer. PATIENTS AND METHODS: * A multicentre, open-label design study was conducted at 22 centres in the US involving patients with: localized, locally advanced or metastatic disease; with a rising prostate-specific antigen (PSA) after definitive local treatment; patients undergoing neoadjuvant hormonal therapy before local therapy (radical prostatectomy, radiation therapy or cryosurgery); and patients in whom intermittent therapy was the planned treatment. * All patients received abarelix for 12 weeks followed by an LHRH agonist (either leuprolide or goserelin) for 8 weeks * The primary efficacy endpoint was achievement and maintenance of castration defined as testosterone <50 ng/dL from day 29 through to day 141 and whether abarelix initiation therapy could eliminate the testosterone surge after two consecutive doses of LHRH agonist therapy. * PSA, LH and follicle-stimulating hormone (FSH) levels were measured and adverse events were monitored. RESULTS: * A total of 176 patients were enrolled into the present study, the majority of whom had localized prostate cancer (82%) and a PSA level <10 ng/mL (62%). * At the end of the abarelix treatment period (day 85), 93.8% of patients achieved castrate levels; during the first week of switch over to the LHRH agonist therapy (days 85-92) the rate was 86.5% and during the week after the second LHRH agonist injection (days 114-12) it was 93.3%. * A small, transient increase in testosterone occurred during the first injection of the LHRH agonist; mean (standard deviation [sd]) values increased from 17 (17.8) ng/dL at day 85 to 37.3 (51.07) ng/dL at day 86. * Mean (sd) PSA levels decreased from 20.5 (56.6) ng/mL at baseline to 3.7 (23.5) ng/mL on day 85 and remained stable throughout the LHRH agonist treatment phase. * Treatment-related adverse events occurred in 84% of patients overall; a similar incidence was reported during the two treatment phases. CONCLUSIONS: * Abarelix initiation therapy results in the desired effect of achieving rapid testosterone suppression; testosterone surges after subsequent LHRH agonist therapy are greatly abrogated or completely eliminated. * This treatment paradigm (abarelix initiation followed by agonist maintenance) obviates the need for an antiandrogen. * Abarelix was well tolerated and no clinically meaningful or novel adverse events were observed during abarelix treatment or in the transition to LHRH agonist maintenance therapy. PMID- 22093776 TI - [Reflections on development of endocrinology and metabolism in China]. PMID- 22093777 TI - [Increased liver fat content triggers metabolic disorders]. PMID- 22093778 TI - [Histone H3 acetylation of tumor necrosis factor-alpha and cyclooxygenase-2 in patients with type 2 diabetes]. AB - OBJECTIVE: To investigate the expression of tumor necrosis factor-alpha (TNF alpha) and cyclooxygenase-2 (COX-2) mRNA and evaluate the status of histone H3 acetylation at TNF-alpha and COX-2 promoter in peripheral blood mononuclear cells (PBMCs) from type 2 diabetics. METHODS: The PBMCs from 12 type 2 diabetics and 12 healthy controls were isolated by Ficoll-Hypaque density gradient centrifugation. The differential expression of TNF-alpha and COX-2 mRNA was measured by real-time PCR (polymerase chain reaction). Chromatin immunoprecipitation analysis was used to detect the status of H3 acetylation at TNF-alpha and COX-2 promoter region. RESULTS: TNF-alpha and COX-2 mRNA were overexpressed in PBMCs from Type 2 diabetics as compared with normal controls (2.28 +/- 0.09 fold and 2.78 +/- 0.26 fold).(P < 0.05). Compared with normal controls, H3 acetylation at the TNF-alpha (1.54 +/- 0.43 vs 0.97 +/- 0.39, P = 0.0094) and COX-2 (1.20 +/- 0.58 vs 0.64 +/- 0.21, P = 0.0161) gene promoter region was elevated in PBMCs from Type 2 diabetic patients. CONCLUSION: Increased H3 acetylation at TNF-alpha and COX-2 promoter in PBMCs from type 2 diabetics may contribute to the pathogenesis of type 2 diabetes through the elevated expressions of TNF-alpha and COX-2. PMID- 22093779 TI - [Effects of early insulin therapy on sterol regulatory element binding protein 1 pathway and lipid accumulation in liver of type 2 diabetic rats]. AB - OBJECTIVE: To explore the effect of early insulin therapy on sterol regulatory element binding protein 1 (SREBP1) pathway and lipid accumulation in liver of type 2 diabetic rats (DM). METHODS: A high-fat diet plus a low-dose of streptozotocin (STZ) was administered to the Sprague-Dawley (SD) rats to create a type 2 diabetic animal model. Then the rats were divided into 3 groups: normal control (NC), DM (untreated diabetic rats) and INS (a 3-week treatment of NPH insulin initiated from day 3 of STZ injection). Insulin was delivered daily by a 3-week subcutaneous injection (6 - 8 U/day). Liver homogenate was prepared. The protein levels of ER stress marker immunoglobulin binding protein (Bip), oxygen regulated protein 150 (ORP150), insulin-induced gene 1 (Insig1), SREBP1 and nuclear SREBP1 (nSREBP1) were assayed by Western blot. Adipose tissue mass was measured. RESULTS: In the DM group, ER (endoplasmic reticulum) stress marker Bip and ORP150 were up-regulated (0.67 +/- 0.02 vs 0.43 +/- 0.01 for Bip; 1.11 +/- 0.04 vs 1.83 +/- 0.03 for ORP150, P < 0.05 for both) and Insig1 decreased (0.25 +/- 0.02 vs 0.80 +/- 0.07, P < 0.05). And the expressions of SREBP1 and nSREBP1 were elevated (1.03 +/- 0.14 vs 0.41 +/- 0.01 for SREBP1; 3.63 +/- 0.77 vs 0.96 +/- 0.20 for nSREBP1, P < 0.05 for both) in comparison with the normal control rats. In the INS group, all aforementioned changes became attenuated or reversed (0.41 +/- 0.04 vs 0.67 +/- 0.02 for Bip; 1.83 +/- 0.03 vs 1.11 +/- 0.04 for ORP150; 0.43 +/- 0.02 vs 0.25 +/- 0.02 for Insig1; 0.46 +/- 0.01 vs 1.03 +/- 0.14 for SREBP1; 1.65 +/- 0.18 vs 3.63 +/- 0.77 for nSREBP1, P < 0.05 for all). Furthermore, adipose tissue mass increased (22.4 g +/- 3.6 g vs 12.0 g +/- 2.6 g, P < 0.05). CONCLUSION: The early insulin therapy induces a fat redistribution from liver to adipose tissue. The mechanism is probably through a reduction of ER stress and a down-regulated pathway of SREBP1 in liver of diabetic rats. PMID- 22093780 TI - [Combined utility of hemoglobin A1c and glycated albumin in diabetic screening]. AB - OBJECTIVE: To assess the validity of combined detection of hemoglobin A1c (HbA1c) and glycated albumin (GA) in diabetic screening. METHODS: A total of 1480 subjects at our out-patient department from March 2007 to December 2009. Those suspected of diabetes or at a high risk of diabetes were enrolled. The study population included 677 males and 803 females with a mean age of 52.7 years. All subjects received an oral glucose tolerance test (OGTT) after a 10-hour fasting. Glycated albumin (GA) and hemoglobin A1c (HbA1c) were measured with liquid enzyme method and high pressure liquid chromatography respectively. RESULTS: (1) According to World Health Organization diabetes diagnosis criteria, there were 562 subjects with normal glucose tolerance (NGT), 411 subjects with impaired glucose regulation (IGR) and 507 subjects with newly diagnosed diabetes mellitus (DM). The level of HbA1c and GA had a rising tendency among NGT, IGR and DM groups (P < 0.01). (2) Pearson correlation analysis demonstrated that HbA1c had a positive association with GA (r = 0.75, P < 0.01). (3) Using OGTT as golden standard of diabetic diagnosis, receiver operator characteristic (ROC) curve indicated that HbA1c and GA were strong predictors of diabetes. The area under curve (AUC) was 0.882 and 0.881 respectively with no significant difference (P > 0.05). (4) The sensitivity of combined use of HbA1c and GA at optimal cut-off points of 6.1% and 17.1% was significantly higher than that of single use of HbA1c or GA in diabetic screening (94.7% vs 81.1%, 88.4%, P < 0.01). CONCLUSION: A combined detection of HbA1c and GA may improve the efficacy of diabetic screening. The subject with HbA1c >= 6.1% or GA >= 17.1% is recommended to undergo OGTT for confirming a diagnosis of diabetes. PMID- 22093781 TI - [Clinicopathologic characteristics and prognosis in young Chinese women with breast cancer]. AB - OBJECTIVE: To analyze the clinicopathologic characteristics and evaluate the prognosis in young Chinese women with breast cancer. METHODS: A total of 1538 female patients with operable primary breast cancer (stage I-III) treated at our hospital from December 1994 to December 2003 were analyzed retrospectively. Among them, 1075 patients (<= 60 yrs) with the complete follow-up data were divided into two groups according to age: young breast cancer group (<= 40 yrs, n = 208) and control group (41 - 60 yrs, n = 867) to analyze the differences in their clinicopathologic characteristics and evaluate the prognosis of both groups. RESULTS: The patients with young breast cancer were more likely to have positive lymph nodes (P = 0.016), a negative expression of ER (estrogen receptor) (P = 0.016) and a positive expression of HER2 (P = 0.001). The 5-year disease-free survival (DFS) rates of young breast cancer group and control group were 73.3% and 84.1% (P < 0.001) and the 5-year overall survival (OS) rates 83.5% and 89.1% (P = 0.004) respectively. Moreover, the patients with young breast cancer had a worse DFS than control group in patients with stage I-II disease but not in those with stage III disease. And <= 40 years was an independent unfavorable prognostic factor of DFS (HR = 1.78, 95%CI: 1.19 - 2.66, P = 0.005) and OS (HR = 1.71, 95%CI: 1.01 - 2.90, P = 0.046) in the patients with stage I-II disease. CONCLUSION: Chinese women with young breast cancer have a worse prognosis, particularly in those with stage I-II disease. PMID- 22093782 TI - [Prevalence and risk factors of retinal arterial atherosclerosis in urban subjects participating in routine physical examinations]. AB - OBJECTIVE: To determine the prevalence and risk factors of atherosclerotic lesions in retinal arteries of an urban population undergoing routine physical examinations. METHODS: Demographic and clinical information of subjects participating in annual routine physical examinations at Peking Union Medical Center from January to October of 2010 were collected and summarized. Univariate and multivariate Logistic regression analyses were conducted to evaluate the demographic and clinical factors associated with retinal arterial atherosclerosis. RESULTS: Among a total of 17 886 non-diabetic adults evaluated during the study period, retinal arterial atherosclerosis was diagnosed in 1721 (9.6%). There were predominantly grade 1 (88%) and grade 2 (11%) lesions. Prevalence of retinal arterial atherosclerosis increased with age. And traditional risk factors for cardiovascular diseases included overweight or obesity, hypertension, dyslipidemia and elevated fasting serum glucose. In a multivariate Logistic regression model, advanced age, male gender, obesity or overweight, hypertension and dyslipidemia were independently associated with a higher risk of retinal arterial atherosclerosis. Hypertension was prevalent in subjects above 40 years old while overweight or obesity had a high prevalence in all age groups. CONCLUSION: Retinal arterial atherosclerosis is common in this urban population. And aging, overweight/obesity and hypertension are the dominant risk factors. Routine physical examination is valuable for both the prevention and an early diagnosis of this disease. PMID- 22093783 TI - [Association of IL-8 gene polymorphisms with inflammatory bowel disease in Chinese patients]. AB - OBJECTIVE: To investigate the association of interleukin 8 (IL-8) gene polymorphisms with the risks of inflammatory bowel disease (IBD). METHODS: Single nucleotide polymorphisms (SNPs) of IL-8 gene at -845 T/C, -738 T/A, -353 A/T, 251 T/A and +678 T/C were analyzed in 183 IBD patients. They included Crohn's disease (CD, n = 41), ulcerative colitis (UC, n = 142) and healthy controls (n = 160). The methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence specific primers (PCR-SSP) were employed. RESULTS: No association was observed between any of these five SNPs in IL-8 gene with the occurrence of IBD. A specific haplotype AAT (-353 A/T, -251 T/A & +678 T/C) was over-represented in UC cases when compared with controls (31.0% vs 23.7%, P = 0.046). But the distributions of this haplotype did not show significant difference between CD cases and controls. CONCLUSION: Our data support a significant but modest association between the AAT haplotype of IL-8 gene and UC (OR = 1.441, 95%CI 1.007 - 2.063). PMID- 22093784 TI - [Influence of minor back trauma on surgical outcomes in patients with thoracic ossification of ligamentum flavum]. AB - OBJECTIVE: To retrospectively explore the influences of minor back trauma on surgical outcomes in patients with thoracic ossification of ligamentum flavum (TOLF) and preliminarily detect its possible causes. METHODS: A total of 94 TOLF patients were divided into two groups according to the absence or presence of minor back trauma: MT (minor trauma, n = 16) and NT (no trauma, n = 78). They were compared in terms of gender, age, duration of symptoms, levels of involvement, numbers of involved segments, ratio of intramedullary signal changes (IMSC), pre- & post-operative JOA (Japanese Orthopedic Association) score, recovery rate (RR) at the final follow-up. Multiple regression analysis was employed to elucidate the causes related with the surgical outcomes. The MT group was further divided into two subgroups according to the intervals between trauma and surgery to clarify the influences of surgical timing on the efficacies. RESULTS: The JOA scores were 4.0 +/- 1.4 and 8.4 +/- 1.7 respectively in MT and NT groups at the final follow-up. The neurological status of patients improved in both groups (MT: P = 0.009, NT: P = 0.000). The patients were younger in MT groups (50 +/- 11 years) than those in NT groups (58 +/- 8 years) (P = 0.046). The ratio of IMSC was higher in MT groups (75.0%) than that in NT groups (25.6%) (P = 0.000). The pre- & post-operative JOA scores were lower in MT groups than those in NT groups (both P = 0.000). Multiple regression analysis revealed that the postoperative JOA score at the final follow-up was positively related with the preoperative JOA score (r = 0.60, P = 0.000) and negatively with trauma and IMSC (r = -1.82 and r = -1.87, P = 0.000) while the final postoperative RR were negatively related with trauma and IMSC (r = -26.26 and r = -33.70, P = 0.000). The surgical timing after trauma did not influence the efficacies (P = 0.147). CONCLUSION: The TOLF patients with minor back trauma have a worse post-operative recovery. A minor trauma might be a risk factor of adverse surgical outcomes. PMID- 22093785 TI - [Short-term efficacy comparison of laparoscopic-assisted versus open distal gastrectomy]. AB - OBJECTIVE: To compare the short-term efficacy of laparoscopic-assisted verus open distal gastrectomy for gastric cancer. METHODS: The data of 29 patients with distal gastric cancer from January 2008 to October 2010 were analyzed. RESULTS: Twenty-eight underwent laparoscopic-assisted distal gastrectomy while 1 was switched to open surgery. The operative duration was (253.1 +/- 32.6) min and the blood loss volume (268.5 +/- 101.4) ml. The postoperative recovery time of gastrointestinal peristalsis was (2.1 +/- 0.6) d. The length of incision was (5.6 +/- 1.6) cm, the hospital stay duration (10.6 +/- 2.4) d and the number of dissected lymph nodes (34.5 +/- 5.2). CONCLUSION: Laparoscopic-assisted distal gastrectomy for gastric cancer is both safe and feasible. And it offers many advantages of minimal invasion, less pain and shorter hospital stay. PMID- 22093786 TI - [Clinical comparative study of neoadjuvant chemotherapy outcome in locally advanced breast cancer: docetaxel versus paclitaxel plus pirarubicin hydrochloride and cyclophosphamide]. AB - OBJECTIVE: To compare the efficacy and toxicity of neoadjuvant chemotherapy of docetaxel with paclitaxel plus pirarubicin hydrochloride (THP) and cyclophosphamide (CTX) in locally advanced breast cancer (LABC). METHODS: A total of 97 LABC cases were randomly divided into 2 groups: docetaxel group (n = 49, taxotere plus THP & CTX) and paclitaxel group (n = 48, paclitaxel plus THP & CTX). Neoadjuvant chemotherapy had four cycles of 21 days each. RESULTS: The clinical and pathological complete remission rates of docetaxel group was 28.6% and 26.5% respectively. They were significantly higher than those of paclitaxel group (10.4% and 8.3%). Furthermore the pathological negative rate of regional lymph node in docetaxel group was also significantly higher than that of paclitaxel group (40.6% vs. 12.9%). However, grade III-IV blood system toxic reaction was found in 71.4% cases, grade II-IV liver dysfunction in 53.1% cases and edema in 24.5% cases among docetaxel group. They were higher than those among paclitaxel group (46.9%, 27.1% & 4.2%). CONCLUSION: Compared with paclitaxel, the combined regimen of docetaxel plus THP and CTX offers better outcomes for locally advanced breast cancer. PMID- 22093788 TI - [An absence of donor TH17 differentiation ameliorates dermal tissue damage]. AB - OBJECTIVE: To explore the functions of TH17 cell in cutaneous graft-versus-host disease (GVHD). METHODS: A model of acute GVHD (aGVHD) was established with a major histocompatibility complex class I/II-disparate allogeneic bone marrow transplantation (BMT). Bone marrow monocytes and splenic T cells from donor C57/BL6 were enriched. The recipient BABL mice were irradiated ((60)Co source) with 7.5 Gy total body irradiation (TBI) and injected with 5 * 10(6) marrow monocytes and 5 * 10(5) T cells. The experimental mice were divided into 3 groups: lethal total body irradiation (TBI); allogeneic bone marrow transplantation (BMT) and recipients of halofuginone (HF). The symptoms of aGVHD were observed daily and detailed histopathologic analyses of recipient skin were performed at Day 6 post-transplantation. And Tri-color flow cytometry (FCM) was performed at Day 6 post-transplantation to measure the levels of interleukin (IL) 17, interferon (IFN)-gamma and TH1/TH17. RESULTS: Clinical GVHD symptoms were observed in recipient mice. The administration of HF to lethally irradiated recipients led to very modest GVHD-induced cutaneous changes manifested predominantly by fur loss. However, the experimental animals receiving only allogeneic BMT showed significant fur loss and pathologic skin conditions. Consistent with the clinical evaluations, the histopathologic results demonstrated significantly increased pathologic cutaneous lesions in recipients undergoing only BMT. The median ratios of TH1/TH17 cells were 17.57 and 5.31 in the HF and BMT groups respectively. The difference had statistical significance (P < 0.05). The serum levels of IL-17 were(1.47 +/- 0.18) and (2.81 +/- 0.19) pg/ml in the TBI and BMT groups respectively (P < 0.05). But IL-17 could not be detected in the HF group. The serum levels of IFN-gamma were (3.86 +/- 0.32), (42.97 +/- 0.42) and (9.89 +/- 0.51) pg/ml in the TBI, BMT and HF groups respectively. The inter-group differences had statistical significance (P < 0.05). CONCLUSION: An absence of TH17 cell may alleviate the cutaneous GVHD but exacerbate the systemic GVHD. PMID- 22093787 TI - [Laparoendoscopic single-site retroperitoneal adrenalectomy:a report of 7 cases]. AB - OBJECTIVE: To summarize our preliminary clinical experiences of laparoendoscopic single-site (LESS) retroperitoneal adrenalectomy. METHODS: Since October 2009 to January 2011, the investigators have performed LESS retroperitoneal adrenalectomy for 7 patients with adrenal tumors. A waist axillary midline incision of around 2 - 3 cm was made and a single incision for inserting a homemade port. Cambridge endo flexible laparoscopic instrument and other common laparoscopic accessories were used during the surgical procedures. RESULTS: LESS retroperitoneal adrenalectomies were technically successful in 6 cases with no extra skin incisions, no conversion into an open procedure or standard laparoscopy. Conversion to standard laparoscopy (3 ports) was inevitable in one case. The reason for conversion was due to tumor size (6 cm). No perioperative complication occurred. The mean operative duration was 139 min (95 - 200 min), the mean volume of blood loss 96 ml (30 - 350 ml) and the mean hospital stay 5 d (3 - 8 d). CONCLUSION: LESS retroperitoneal adrenalectomy is technically feasible and safe for the treatment of small adrenal tumors. PMID- 22093789 TI - [Transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor gene for the treatment of pulmonary hypertension in rats]. AB - OBJECTIVE: To explore the therapeutic effect and the mechanism of marrow mesenchymal stem cells (MMSCs) transfected with vascular endothelial growth factor (VEGF) gene in the treatment of pulmonary hypertension in rats. METHODS: MMSCs from the bone marrow of Sprague-Dawley rats were isolated, cultured and propagated in vitro. pIRES2-EGFP-VEGF165 was transfected into MMSC. The healthy male SD rats were divided randomly into 4 groups: normal control group, pulmonary hypertension model group, MMSCs transplantation group and transfer gene transplantation group. A single subcutaneous monocrotaline (50 mg/kg) was injected to induce the model of pulmonary hypertension. The normal control group received a single subcutaneous dose of L-DMEM (low glucose Dulbecco's modified Eagle's medium). All four groups of rats were fed similarly. At Day 21 post modeling, 5 * 10(6) MMSCs in l ml L-DMEM were injected into the MMSC group. 5 * 10(5) MMSC transfected by pIRES2-EGFP-VEGF165 were injected into the gene transplantation group. A same volume L-DMEM solution was also injected into the pulmonary hypertension model group and normal control group. The parameters of right ventricular systolic pressure (RVSP), right ventricular hypertrophy index, blood gas analysis and microstructure as well as pulmonary microvascular changes were observed after 30 days. RESULTS: At Day 30 post-transplantation of MMSCs, the outcomes were as follows: RVSP was (30.2 +/- 2.1) and (29.2 +/- 1.1) mm Hg (1 mm Hg = 0.133 kPa) in the MMSCs transplantation and gene transplantation groups respectively. The right ventricular hypertrophy indices were (37.9 +/- 3.2)% and (27.2 +/- 3.4)% respectively. The media thickness of pulmonary artery (MT) was (21.3 +/- 3.4) and (14.3 +/- 2.8) um respectively. The ratios of vascular area to total arterial area (V/T) were (39.3 +/- 4.3)% and (43.0 +/- 1.5)% respectively. As compare with the pulmonary hypertension model group, the above parameters were of statistical significances (P < 0.01). A comparison of right ventricle hypertrophy index, MT and V/T was of statistical significance between MMSC and gene transplantation groups (P < 0.05). The blood gas analysis of the MMSCs transplantation and gene transplantation groups were better than the pulmonary hypertension mode group. Ultramicrostructure showed that neovascularization and small pulmonary arterial repair appeared in two transplantation groups. CONCLUSION: MMSCs transfected by pIRES2-EGFP-VEGF165 transplantation may improve and reverse the MCT-induced progress of pulmonary hypertension in rats. And it is better than the MMSC transplantation. The potential mechanism is through arterial repair and neovascularization. PMID- 22093790 TI - [Establishment and characterization of serial subpopulations with highly metastatic potential via different metastatic routes]. AB - OBJECTIVE: To establish the serial cell lines, derived from the same parental gallbladder cancer cell line GBC-SD, with highly metastatic potential via different routes and characterize their biological behaviors to understand the different metastasis mechanisms via lymph and blood. METHODS: The spleen-liver metastasis model and footpad-inguinal lymph node metastasis model were established. GBC-SD was injected into spleen or footpad of nude mice. Then the highly metastasized subpopulations via lymph and blood were isolated. Their differences in morphology, genetic background, proliferation, migration, invasion and adhesion were revealed by comparing the lymphatic-disseminating and hematogenous-disseminating subpopulations with parental cells. RESULTS: The lymphatic-disseminating and hematogenous-disseminating subpopulations were successfully isolated and designated as GBC-SD/HL and GBC-SD/M3 respectively. They demonstrated the identical genetic background with GBC-SD. In comparison with parental cells, the hematogenous-disseminating subpopulation was morphologically characterized with epithelial-mesenchymal transition (EMT) while it was not shown in the lymphatic-disseminating subpopulation. Furthermore, the hematogenous-disseminating subpopulation showed the strongest migrating capacity but the lymphatic-disseminating subpopulation demonstrated a stronger invasive and adhesive ability. CONCLUSION: The whole parental cell GBC-SD, hematogenous metastasized subpopulation GBC-SD/M3 and lymphatic-disseminating subpopulation GBC-SD/HL is an ideal tool for metastatic mechanism study of gallbladder cancer. EMT plays an important role in hematogenous metastasis while lymphatic metastasis relies more on enhanced invasiveness and adhesion. It may be a target for interfering the lymphatic metastasis of gallbladder cancer. PMID- 22093791 TI - [Effects of simvastatin plus all-trans retinoic acid on WT1/hDMP1 gene expression profiles of human promyelocytic leukemia cell line NB4]. AB - OBJECTIVE: To investigate the effects of simvastatin (SV) plus all-trans retinoic acid (ATRA) on the proliferation, differentiation, apoptosis and WT1/hDMP1 gene expression profiles of human promyelocytic leukemia cell line NB4. METHODS: The NB4 cell was incubated with simvastatin and ATRA alone or in combination. And the NB4 cell without any treatment was adopted as a normal control. The cells of different groups were collected at 24, 48 and 72 h post-incubation. Their morphological changes were observed after Wright staining. The method of MTT was employed to assay the growth inhibition rate and flow cytometry was used to detect the early-stage ratios of apoptosis and cell necrosis. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the WT1/hDMP1 gene expression levels. RESULTS: The cell inhibition rates increased gradually (F = 7.15, P = 0.000) at 15, 10 and 5 umol/L SV respectively. And so did the expression levels of CD11b (F = 3.41, P = 0.014) and Annexin-V (F = 43.38, P = 0.000). However the expression levels of WT1 decreased gradually (F = 5.35, P = 0.001) reversely with the elevated levels of hDMP1 (F = 22.61, P = 0.000). Furthermore the NB4 cell exhibited the most significant changes at 15 umol/L SV. After a 72-hour incubation, the expression levels of CD11b (89.46% +/- 9.13%)and hDMP1 (626.9 +/- 56.9) in NB4 cells at 15 umol/L SV plus 0.5 umol/L ATRA were significantly higher than those with ATRA(71.27% +/- 7.27%, P = 0.000 and 421.8 +/- 38.3, P = 0.003 in each) and SV alone(62.41% +/- 6.37%, P = 0.003 and 241.4 +/- 21.9, P = 0.003 in each). A combination of 15 umol/L SV with 0.5 umol/L ATRA displayed obvious interactions with the expressions of CD11b and hDMP1 (F = 4.09, P = 0.025 and F = 29.58, P = 0.000 in each). And there was no significant interaction for cell inhibition rates and Annexin-V expression. CONCLUSION: Simvastatin in vitro inhibits the proliferation of NB4 cell, induces its differentiation and promotes its apoptosis. And the lowered expression of WT1 has a dose-dependent correlation with the elevated expression of hDMP1. It indicates that simvastatin has the synergistic in vitro anti-promyelocytic potency. PMID- 22093792 TI - [Pathogenic mechanism of CD8(+)CD28(-)T cell and the effect of dexamethasone in asthmatic mouse]. AB - OBJECTIVE: To explore whether or not CD8(+)CD28(-)T cell play a pathogenic role in asthma and detect the effects of dexamethasone (DXM). METHODS: A total of 30 mice were randomly divided into 3 groups: asthmatic group, DXM group and control group (n = 10 each). The asthmatic and DXM groups were sensitized twice and inhaled ovalbumin. The DXM Group received an intraperitoneal injection of DXM 1mg/kg before inhaling ovalbumin. After successful modeling, 3 mice were selected randomly from each group to measure the airway responsiveness. Also a bronchoalveolar lavage cytological study was performed and lung tissue sections were prepared for histopathologic examination to evaluate the airway inflammation. The content of IgE in bronchoalveolar lavage fluid (BALF) was detected with a murine IgE ELISA kit. And the fractions of CD8(+)CD28(-)T cell of peripheral blood and BALF were tested by flow cytometry to analyze the correlation between IgE, eosinophils (EOS) of BALF and CD8(+)CD28(-)T cell of blood. RESULTS: The airway hyperresponsiveness in asthmatic and DXM groups were significantly higher than that in the control group. The number of total cells and EOS of BALF in the asthmatic group [(5.56 +/- 4.06) * 10(2)/L; (3.29 +/- 2.23) * 10(2)/L] were significantly higher than that in control group [(0.91 +/- 0.65) * 10(2)/L, P = 0.003; (0.43 +/- 0.37) * 10(2)/L, P = 0.001] and DXM group [(2.59 +/- 1.69) * 10(2)/L, P = 0.044; (1.11 +/- 0.73) * 10(2)/L, P = 0.008]; while the DXM group was insignificantly higher than the control group (P = 0.234, P = 0.363). There were significant differences in the contents of IgE of BALF for the asthmatic, DXM and control groups [(23.85 +/- 5.97) g/L, (13.15 +/- 2.22) g/L, (6.54 +/- 1.03) g/L, F = 38.558, P = 0.000]. The percentages of CD8(+)CD28( )T cell in peripheral blood in asthmatic and DXM groups [(18.68 +/- 4.12)% and (13.43 +/- 2.91)%] were significantly higher than those in control mice [(8.43 +/ 4.60)%, both P < 0.05]. The percentages of CD8(+)CD28(-)T cell of BALF in asthmatic group and DXM group [(1.25 +/- 0.40)% and (0.66 +/- 0.49)%] were also significantly higher than those in control mice [(0.21 +/- 0.19)%, both P < 0.05]. The percentages of CD8(+)CD28(-)T cell of blood and BALF in the DXM mice were significantly lower than those in asthmatic group. The correlations between IgE (r = 0.864, P = 0.012), EOS (r = 0.804, P = 0.029) and CD8(+)CD28(-)T cell were significant. CONCLUSION: The fraction of CD8(+)CD28(-)T cell is closely correlated with the inflammation of asthmatic airway. The airway hyperresponsiveness and inflammation in asthmatic mice may be relieved by DXM through its effect of inhibiting the expression of CD8(+)CD28(-) T cell. PMID- 22093793 TI - [Protection of penehyclidine hydrochloride on renal tissue injury induced by limb ischemia/reperfusion]. AB - OBJECTIVE: To evaluate the protection of penehyclidine hydrochloric postconditioning on HIF-1alpha (hypoxia-inducible factor-1alpha) in renal tissue injury induced by lower limb ischemia/reperfusion (I/R). METHODS: A total of 72 adult male Wistar rats weighing 230 - 250 g were randomly divided into 3 groups: control (group C), limb ischemia-reperfusion (group R/I) and penehyclidine hydrochloride postconditioning (group P). The animals were anesthetized by inhaling 2% isoflurane and blood flow of bilateral lower limbs was blocked with rubber bands for 3 h in groups P and R/I. In group P, penehyclidine hydrochloride 0.15 mg/kg was injected via caudal vein at 3 min pre-reperfusion. After sacrificing, their kidneys were removed at 3 h of ischemia and 1, 3, 6 h of reperfusion respectively. The blood urea nitrogen (BUN) and creatinine (Cr) were detected by colorimetric method, plasma tumor necrosis factor-alpha (TNF-alpha) by ELISA (enzyme-linked immunosorbent assay) and HIF-1alpha of renal tissue by immunohistochemistry. Renal pathological changes were observed under light microscope. RESULTS: Compared with group C, the serum levels of BUN and Cr increased while TNF-alpha and HIF-1alpha were up-regulated in groups I/R and P (P < 0.05). As compared with group I/R, the serum levels of BUN, Cr and MDA decreased while TNF-alpha and HIF-1alpha were down-regulated in group P. [at T2: (15.10 +/- 1.88) mmol/L vs (19.46 +/- 2.76) mmol/L, (113 +/- 10) umol/L vs (143 +/- 11) umol/L, (13.8 +/- 1.7) nmol/g vs (15.5 +/- 1.8) nmol/g, (53.1 +/- 3.1) ng/L vs (53.9 +/- 4.8) ng/L, 0.298 +/- 0.015 vs 0.471 +/- 0.032, all P < 0.05]. CONCLUSION: Penehyclidine hydrochloride can down-regulate the expression of HIF 1alpha and attenuate the renal injury induced by lower limb I/R. And the mechanisms may be through inhibiting the inflammatory reactions, reducing the release of oxygen free radicals and improving the conditions of hypoxia and ischemia. PMID- 22093794 TI - Automatic model-based roentgen stereophotogrammetric analysis (RSA) of total knee prostheses. AB - Conventional radiography is insensitive for early and accurate estimation of the mal-alignment and wear of knee prostheses. The two-staged (rough and fine) registration of the model-based RSA technique has recently been developed to in vivo estimate the prosthetic pose (i.e, location and orientation). In the literature, rough registration often uses template match or manual adjustment of the roentgen images. Additionally, possible error induced by the nonorthogonality of taking two roentgen images neither examined nor calibrated prior to fine registration. This study developed two RSA methods for automate the estimation of the prosthetic pose and decrease the nonorthogonality-induced error. The predicted results were validated by both simulative and experimental tests and compared with reported findings in the literature. The outcome revealed that the feature-recognized method automates pose estimation and significantly increases the execution efficiency up to about 50 times in comparison with the literature counterparts. Although the nonorthogonal images resulted in undesirable errors, the outline-optimized method can effectively compensate for the induced errors prior to fine registration. The superiority in automation, efficiency, and accuracy demonstrated the clinical practicability of the two proposed methods especially for the numerous fluoroscopic images of dynamic motion. PMID- 22093795 TI - Effects of tendon and muscle belly dissection on muscular force transmission following tendon transfer in the rat. AB - The aim of the present study was to quantify to what extent the scar tissue formation following the transfer of flexor carpi ulnaris (FCU) to the distal tendon of extensor carpi radialis (ECR) affects the force transmission from transferred FCU in the rat. Five weeks after recovery from surgery (tendon transfer group) and in a control group, isometric length-force characteristics of FCU were assessed for progressive stages of dissection: (i) with minimally disrupted connective tissues, (ii) after full dissection of FCU distal tendon exclusively, and (iii) after additional partial dissection of FCU muscle belly. Total and passive length-force characteristics of transferred and control FCU changed significantly by progressive stages of dissection. In both groups, tendon dissection decreased passive FCU force exerted at the distal tendon, as well as the slope of the length-force curve. However, force and slope changes were more pronounced for transferred FCU compared to controls. No additional changes occurred after muscle belly dissection. In contrast, total force increased in transferred FCU following both tendon and muscle belly dissection at all lengths studied, while dissection decreased total force of control FCU. In addition, after tendon and muscle belly dissection, we found decreased muscle belly lengths at equal muscle-tendon complex lengths of transferred FCU. We conclude that scar tissue limits the force transmission from transferred FCU muscle via the tendon of insertion to the skeleton, but that some myofascial connectivity of the muscle should be classified as physiological. PMID- 22093796 TI - [Clopidogrel induced thrombotic thrombocytopenic purpura]. AB - INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. Drug-induced TTP is uncommon and we report a TTP associated with the use of clopidogrel. CASE REPORT: We report a 50-year-old man who presented with acute myocardial infarction and received clopidogrel therapy. He developed acute TTP ten days after clopidogrel onset. Imputability of the drug was demonstrated during a reintroduction test. Deficiency of ADAMTS 13 was confirmed and autoantibodies against ADAMTS 13 were detected. Complete remission was obtained after 24 plasma exchange sessions and adjunction of corticosteroids. CONCLUSION: Drug-induced TTP are probably immunologic, as was demonstrated in our patient. Clinicians should be aware of this possible uncommon adverse effect of clopidogrel because prompt therapy is imperative for life saving. PMID- 22093797 TI - [Emotion perception in neurodegenerative disorders]. PMID- 22093798 TI - [Central nervous system involvement in systemic sclerosis]. AB - Systemic sclerosis is a connective disease usually known to spare the central nervous system. This has been much debated by recent imaging studies. We report a 56-year-old woman followed-up for systemic sclerosis since 2005. Four years later, she presented with cerebellar and pyramidal syndrome. Magnetic resonance imaging showed signs of cerebral vasculitis. The patient was treated by corticosteroids and cyclophosphamide pulses followed by azathioprine for maintenance therapy. Clinical and radiological outcomes were favourable. In patients with systemic sclerosis and neurological symptoms, abnormalities in the cerebral magnetic resonance imaging may, in the absence of another obvious etiology, indicate a central nervous system involvement associated with this systemic disorder. PMID- 22093800 TI - Weaponry, color, and contest success in the jumping spider Lyssomanes viridis. AB - Weaponry and color badges are commonly theorized to function as visual signals of aggressiveness or fighting ability. However, few studies have supported a signaling function of weaponry, and the role of color in invertebrate competitive interactions remains virtually unexplored. Jumping spiders (Salticidae) make excellent invertebrate models for studying weaponry and color because males of many species are colorful and possess exaggerated chelicerae, which are used as weapons in escalated contests. To determine whether color or weaponry might function as visual signals in male-male competitions, we investigated relationships between contest success, cheliceral length, and red coloration in Lyssomanes viridis. Males having longer chelicerae than their opponents were significantly more likely to win (p=0.0008). Males who won, despite being smaller than their opponents, had significantly less red chelicerae than their opponents (p=0.01). Male and female cheliceral length, as well as foreleg length, correlated tightly with body size. Cheliceral and foreleg length showed significantly stronger positive allometry in males than in females. We conclude that male chelicerae and forelegs are under strong positive selection for their use in physical fights and/or as visual signals of fighting ability. PMID- 22093799 TI - Evolution and connectivity in the world-wide migration system of the mallard: inferences from mitochondrial DNA. AB - BACKGROUND: Main waterfowl migration systems are well understood through ringing activities. However, in mallards (Anas platyrhynchos) ringing studies suggest deviations from general migratory trends and traditions in waterfowl. Furthermore, surprisingly little is known about the population genetic structure of mallards, and studying it may yield insight into the spread of diseases such as Avian Influenza, and in management and conservation of wetlands. The study of evolution of genetic diversity and subsequent partitioning thereof during the last glaciation adds to ongoing discussions on the general evolution of waterfowl populations and flyway evolution. Hypothesised mallard flyways are tested explicitly by analysing mitochondrial mallard DNA from the whole northern hemisphere. RESULTS: Phylogenetic analyses confirm two mitochondrial mallard clades. Genetic differentiation within Eurasia and North-America is low, on a continental scale, but large differences occur between these two land masses (F(ST) = 0.51). Half the genetic variance lies within sampling locations, and a negligible portion between currently recognised waterfowl flyways, within Eurasia and North-America. Analysis of molecular variance (AMOVA) at continent scale, incorporating sampling localities as smallest units, also shows the absence of population structure on the flyway level. Finally, demographic modelling by coalescence simulation proposes a split between Eurasia and North-America 43,000 to 74,000 years ago and strong population growth (~100fold) since then and little migration (not statistically different from zero). CONCLUSIONS: Based on this first complete assessment of the mallard's world-wide population genetic structure we confirm that no more than two mtDNA clades exist. Clade A is characteristic for Eurasia, and clade B for North-America although some representatives of clade A are also found in North-America. We explain this pattern by evaluating competing hypotheses and conclude that a complex mix of historical, recent and anthropogenic factors shaped the current mallard populations. We refute population classification based on flyways proposed by ornithologists and managers, because they seem to have little biological meaning. Our results have implications for wetland management and conservation, with special regard to the release of farmed mallards for hunting, as well as for the possible transmission of Avian Influenza by mallards due to migration. PMID- 22093801 TI - Delayed fetal hemoglobin switching in subjects with KLF1 gene mutation. AB - Variations at the KLF1 gene have been associated with a series of human erythroid phenotypes including the In-(Lu) phenotype, hereditary persistence of fetal hemoglobin, congenital dyserythropoietic anemia, borderline HbA(2) and increased red blood cell protoporphyrin. Natural mutations have shown that KLF1 regulates gamma globin gene expression and its role in the switching from fetal to adult globin expression has been suggested by experimental studies. In this paper we report that subjects with S270X KLF1 mutations show a decrease of HbF levels with increasing age, supporting in vivo the role of KLF1 in hemoglobin switching in humans. PMID- 22093802 TI - Successful serology-based intervention to increase protection against vaccine preventable diseases in liver-transplanted children: a 19-yr review of the Swiss national reference center. AB - As children referred for OLT in Switzerland were not vaccinated optimally, new guidelines were developed and recommended to base catch-up immunization on serum antibody titers against vaccine-preventable diseases, before and after OLT. We measure the results of this serology-based intervention by comparing vaccine coverage and antibody titers in the pre- (1990-2002, P1) and post-intervention (2003-2008, P2) cohorts in a quality control project. Forty-four P1 and 30 P2 children were evaluated. At pre-OLT visit, D, T, SPn, and MMR serologies were checked more frequently in P2 than P1 (p < 0.05). More P2 children were up-to date for DTaP and MMR (p < 0.05) or had received >=1 dose of HBV, HAV, SPn, and VZV vaccines (p < 0.05). One yr post-OLT, DT, SPn, MMR, and VZV serologies were more frequently checked (p < 0.05), and antibody titers were higher for DT and HAV (p < 0.05) in P2. Gender, age, or diagnosis did not explain these differences. Among P2 patients, pre- and post-OLT titers for D, T, Hib, HBV, SPn14, and SPn19 were correlated (p < 0.05 for all). Protection against vaccine preventable diseases of high-risk children like OLT patients can be significantly improved by serology-based intervention for vaccine-preventable diseases. PMID- 22093803 TI - Scaling and structure of dicotyledonous leaf venation networks. AB - There have been numerous attempts to derive general models for the structure and function of resource delivery networks in biology. Such theories typically predict the quantitative structure of vascular networks across scales. For example, fractal branching models of plant structure predict that the network dimensions within plant stems or leaves should be scale-free. However, very few empirical examples of such networks are available with which to evaluate such hypotheses. Here, we apply recently developed leaf network extraction software to a global leaf dataset. We find that leaf networks are neither entirely scale-free nor governed entirely by a characteristic scale. Indeed, we find many network properties, such as vein length distributions, which are governed by characteristic scales, and other network properties, notably vein diameter distributions, which are typified by power-law behaviour. Our findings suggest that theories of network structure will remain incomplete until they address the multiple constraints on network architecture. PMID- 22093804 TI - Seasonal influenza vaccination knowledge, risk perception, health beliefs and vaccination behaviours of nurses. AB - The relationship between knowledge, risk perceptions, health belief towards seasonal influenza and vaccination and the vaccination behaviours of nurses was explored. Qualified nurses attending continuing professional education courses at a large London university between 18 April and 18 October 2010 were surveyed (522/672; response rate 77.7%). Of these, 82.6% worked in hospitals; 37.0% reported receiving seasonal influenza vaccination in the previous season and 44.9% reported never being vaccinated during the last 5 years. All respondents were categorized using two-step cluster analyses into never, occasionally, and continuously vaccinated groups. Nurses vaccinated the season before had higher scores of knowledge and risk perception compared to the unvaccinated (P<0.001). Nurses never vaccinated had the lowest scores of knowledge and risk perception compared to other groups (P<0.001). Nurses' seasonal influenza vaccination behaviours are complex. Knowledge and risk perception predict uptake of vaccination in nurses. PMID- 22093805 TI - [Focus on beta-blockers for vascular specialists in 2012]. AB - Since they were launched on the market in 1964, cardiovascular indications for beta-blockers have been validated and accepted worldwide. Numerous studies and meta-analysis have confirmed their benefits. They reduce mortality in post infarction and acute coronary syndrome populations and also in people with stable coronary heart disease. Moreover, heart failure with systolic left ventricular dysfunction is a major indication for this therapeutic class, providing a 30% decrease in mortality. In patients with permanent atrial fibrillation, beta blockers are recommended for rate control. In hypertension patients, first-line drug treatment with beta-blockers is currently discussed. Indeed, several studies have shown that patients randomized in the beta-blocker arms experienced more coronary heart and cerebrovascular diseases than comparators. Their lesser effect on central blood pressure decrease could partially explain those results. Nevertheless, beta-blockers are still considered as first-line drugs for hypertension in the French and European guidelines. Long-term comparative studies focusing on central blood pressure are needed. Concerning the other indications for beta-blockers in vascular diseases, their use perioperatively to reduce surgical cardiovascular risk raised much hope, but the most recent results are disappointed and even suggest possible higher mortality. Finally, except for patients with critical ischemia of the lower limbs, presence of peripheral artery disease should probably be considered as a condition favoring their prescription. PMID- 22093806 TI - Chronic insomnia, quality-of-life, and utility scores: comparison with good sleepers in a cross-sectional international survey. AB - BACKGROUND: Chronic insomnia has a recognized impact on health-related quality-of life (HRQoL) but data on utility scores across countries are lacking. The objective of the present study was to assess health related quality of life (HRQoL) and utility scores in individuals from three different countries (USA, France, and Japan), comparing sufferers of chronic insomnia to good sleepers. METHODS: A cross-sectional survey (SLEEPI-i) of 4067 persons in the US (n=1298; 478 good sleepers and 820 patients with insomnia), France (n=1858; 998 good sleepers and 860 patients with insomnia) and Japan (n=911; 506 good sleepers and 405 patients with insomnia). Enrollment and data collection using consumer panels were web-based in the US and France, and gathered via a postal survey in Japan. People with chronic insomnia (>6 months) were selected based on Insomnia Severity Index scores (ISI). Severity of insomnia was assessed using the ISI score and HRQoL was assessed using the self-administered Short-Form SF-36 Health Survey. Utility scores were derived using the algorithm developed by Brazier et al. Multivariate analyses were used to adjust for potential confounding factors. RESULTS: In all countries, people with chronic insomnia (40% treated) reported lower SF-36 scores in each of eight domains compared with good sleepers (P<.0001). Chronic insomnia was associated with significantly lower utility scores compared with good sleepers (mean scores 0.63 versus 0.72 in the US, 0.57 versus 0.67 in France, and 0.67 versus 0.77 in Japan, P<.0001). CONCLUSIONS: This survey suggests that chronic insomnia is associated with significant impairment of HRQoL and decreased utilities across the different geographical regions studied. PMID- 22093807 TI - A pro-inflammatory role for A20 and ABIN family proteins in human fibroblast-like synoviocytes in rheumatoid arthritis. AB - Circuit of chronic inflammation in the joints of rheumatoid arthritis (RA) starts from the production of inflammatory cytokines by fibroblast-like synoviocytes (FLS) stimulated by TNFalpha produced by inflammatory cells mainly composed of macrophages. In this context, TNFalpha/NF-kappaB pathway plays an essential role for the transcription of pro-inflammatory cytokines. Here we show that the kinetics of pro-inflammatory cytokine genes induced by TNFalpha in FLS from RA was synchronized with that of A20, ABIN1, and ABIN3 that have been thought as negative regulators for NF-kappaB activation. Furthermore, based on this finding, we could tentatively categorize the RA-FLS into two groups; TNFalpha low responder and high-responder FLS. The high responders that have abundant mRNA levels of NF-kappaB inhibitory molecules were also accompanied with the marked induction of the pro-inflammatory cytokines by the stimulation with TNFalpha. The low responders RA-FLS did not show this property, nor did FLS from osteoarthritis. Phosphorylation dependent degradation of IkappaBalpha as well as NF-kappaB activation upon stimulation with TNFalpha was significantly enhanced in the high-responder FLS lines. Surprisingly, single transfection of each NF-kappaB inhibitor was enough to facilitate the transcription of pro-inflammatory cytokines, suggesting that there is an unknown pro-inflammatory function for A20 and ABIN family proteins in RA-FLS. PMID- 22093808 TI - Genetically modified sugarcane for bioenergy generation. AB - Sugarcane breeding has significantly progressed over the past 30 years, but attempts to further increase crop yield have been limited due to the complexity of the sugarcane genome. An alternative to boost the crop yield is the introduction of genes encoding desirable traits in the elite sugarcane cultivars. Genetically modified sugarcane with increased yield and pest and disease resistance has already proven its value not only by the increased sugar content but also for the improvement of the crop performance. However, transgene stability is still a challenge since transgene silencing seems to occur in a large proportion of genetically modified sugarcane plants. In addition, regulatory issues associated with the crop propagation model will also be a challenge to the commercial approval of genetically modified sugarcane. PMID- 22093809 TI - Fusion primer and nested integrated PCR (FPNI-PCR): a new high-efficiency strategy for rapid chromosome walking or flanking sequence cloning. AB - BACKGROUND: The advent of genomics-based technologies has revolutionized many fields of biological enquiry. However, chromosome walking or flanking sequence cloning is still a necessary and important procedure to determining gene structure. Such methods are used to identify T-DNA insertion sites and so are especially relevant for organisms where large T-DNA insertion libraries have been created, such as rice and Arabidopsis. The currently available methods for flanking sequence cloning, including the popular TAIL-PCR technique, are relatively laborious and slow. RESULTS: Here, we report a simple and effective fusion primer and nested integrated PCR method (FPNI-PCR) for the identification and cloning of unknown genomic regions flanked known sequences. In brief, a set of universal primers was designed that consisted of various 15-16 base arbitrary degenerate oligonucleotides. These arbitrary degenerate primers were fused to the 3' end of an adaptor oligonucleotide which provided a known sequence without degenerate nucleotides, thereby forming the fusion primers (FPs). These fusion primers are employed in the first step of an integrated nested PCR strategy which defines the overall FPNI-PCR protocol. In order to demonstrate the efficacy of this novel strategy, we have successfully used it to isolate multiple genomic sequences namely, 21 orthologs of genes in various species of Rosaceace, 4 MYB genes of Rosa rugosa, 3 promoters of transcription factors of Petunia hybrida, and 4 flanking sequences of T-DNA insertion sites in transgenic tobacco lines and 6 specific genes from sequenced genome of rice and Arabidopsis. CONCLUSIONS: The successful amplification of target products through FPNI-PCR verified that this novel strategy is an effective, low cost and simple procedure. Furthermore, FPNI PCR represents a more sensitive, rapid and accurate technique than the established TAIL-PCR and hiTAIL-PCR procedures. PMID- 22093810 TI - The interplay between sulphur and selenium metabolism influences the intracellular redox balance in Saccharomyces cerevisiae. AB - Selenium (Se) is an essential element for most eukaryotic organisms, including humans. The balance between Se toxicity and its beneficial effects is very delicate. It has been demonstrated that a diet enriched with Se has cancer prevention potential in humans. The most popular commercial Se supplementation is selenized yeast, which is produced in a fermentation process using an inorganic source of Se. Here, we show that the uptake of Se, Se toxic effects and intracellular Se-metabolite profile are largely influenced by the level of sulphur source supplied during the fermentation. A Yap1-dependent oxidative stress response is active when yeast actively metabolizes Se, and this response is linked to the generation of intracellular redox imbalance. The redox imbalance derives from a disproportionate ratio between the reduced and oxidized forms of glutathione and also from the influence of Se metabolism on the central carbon metabolism. The observed increase in glycerol production rate, concomitant with the inhibition of ethanol formation in the presence of Se, can be ascribed to the occurrence of redox imbalance that triggers glycerol biosynthesis to replenish the pool of NAD(+) . PMID- 22093811 TI - Human African trypanosomiasis in Angola: clinical observations, treatment, and use of PCR for stage determination of early stage of the disease. AB - Biological and clinical observations are described for 224 patients infected by human African trypanosomiasis (HAT) in Angola in 2007 and 2008. Seven patients were initially classified in stage 1 (S1), 17 intermediate stage (IS) (WBC <20 lymphocytes/MUl with absence of trypanosomes in cerebrospinal fluid (CSF) and no neurological signs), and 200 in stage 2 (S2). Out of 224 patients, 165 (73.6%) presented one or more neurological signs. During treatment with eflornithine, six deaths of S2 patients occurred, five of which were because of an encephalopathy syndrome. Nine patients were diagnosed with a relapse or suspected treatment failure during the follow-up: eight patients after treatment with eflornithine (relapse rate 4.1%) and one patient after pentamidine (6.6%). The contribution of PCR for stage determination evaluated for S1 and IS confirms the difficulty of stage determination, as one S1 patient and two IS patients were carriers of trypanosomes detected a posteriori by PCR in CSF but were treated with pentamidine while follow-up did not confirm treatment efficacy. Since 2001 in Angola, either by passive or active mode detection, approximately 80% of the new cases every year were in S2, whereas the annual number of cases has regressed, probably because the transmission of HAT is decreasing. However, stage determination and treatment remain two major issues for the chronic form of sleeping sickness. PMID- 22093812 TI - Pilot assessment of supply chains for pharmaceuticals and medical commodities for malaria, tuberculosis and HIV infection in Ethiopia. AB - To obtain preliminary data on the drug supply management system in Ethiopia, selected facilities were assessed for the availability of essential drugs and commodities for malaria, TB and HIV. Of the 48 surveyed hospitals and health centers, 9 (19%), 9 (19%) and 10 (21%) did not have malaria, TB or HIV drugs, respectively. Similarly, of 27 health posts, 9 (33%) and 6 (22%) did not have rapid diagnostic tests and antimalarial drugs, respectively. The findings indicated an inadequate availability of essential drugs and commodities in the surveyed facilities as well as weaknesses in human resources and training. Assessments of commodity supply chains to ensure operational program success and impact are important. PMID- 22093813 TI - Differences in cytochrome P450 enzyme activities between fish and crustacea: relationship with the bioaccumulation patterns of polychlorobiphenyls (PCBs). AB - Variations in cytochrome P450 enzyme (CYPs) distribution and function between animal groups could result in differential metabolism and elimination kinetics for certain contaminants. Although a number of studies have suggested that differences in polychlorobiphenyl (PCB) accumulation profiles between crustacea and fish might result from differential CYP patterns, the relationship between PCB bioaccumulation and CYP capacities has not been demonstrated in these organisms. In the present study we investigated the hepatic microsomal catalytic activities in three deep-sea fish species, Alepocephalus rostratus (Alepocephalidae), Coelorinchus mediterraneus (Macrouridae), and Lepidion lepidion (Moridae), and the decapod crustacean Aristeus antennatus (Decapoda), using six fluorescent CYP-mediated substrates, namely ER (7-ethoxyresorufin), PR (7-pentoxyresorufin), BR (7-benzyloxyresorufin), CEC (3-cyano-7-ethoxycoumarin), DBF (dibenzylfluorescein) and BFC (7-benzyloxy-4-trifluoromethylcoumarin). Furthermore, we related the metabolic activities to the accumulation patterns of 41 PCB congeners in the muscle of these organisms. The results indicated a marked difference in the presence and activities of CYP isoforms between fish and the crustacean A. antennatus. Liver microsomes of the three selected fish species were capable of metabolizing all six CYP-mediated substrates and enzymes were identified as primarily belonging to CYP1A and CYP3A subfamilies. In contrast, hepatopancreas microsomes from A. antennatus only showed activity for PR and DBF substrates, generally related to mammalian CYP2-like enzymes. Furthermore, a direct relationship between metabolic activities and PCB accumulation profiles could be established. Results revealed that A. antennatus accumulated significantly higher proportions of PCBs 28, 52, 118, 138, 158 and 169 than fish, which is in accordance with the previously observed lack of CYP1A-like biotransformation capacities. Moreover, A. antennatus exhibited lower levels of PCBs 87, 149, 153, 170, 180, 183, 194 and 206 indicating that this crustacean is able to metabolize congeners considered mammalian CYP2B inducers. Hence, the present findings highlight the role of CYP-mediated metabolism in the congener specific accumulation of PCBs in aquatic organisms and stress the need to further investigate quantitative and qualitative differences in xenobiotic metabolism among animal groups. PMID- 22093814 TI - Leflunomide for cytomegalovirus: bench to bedside. AB - Cytomegalovirus (CMV) remains a major cause of morbidity and mortality among transplant recipients, frequently engaging the clinician in a struggle to balance graft preservation with control of CMV disease. Leflunomide has been shown to have immunosuppressive activity in experimental allograft models together with antiviral activity inhibiting CMV both in vitro and in vivo. Data are emerging about its potential role in ganciclovir-sensitive and -resistant CMV, primarily by virtue of a unique mechanism inhibiting virion assembly, as opposed to inhibition of viral DNA synthesis by current agents. This review aims to put in perspective, the knowledge acquired in the last decade or so on leflunomide for CMV. Evidence suggests that it might have activity against human CMV with good oral bioavailability and, more importantly in the resource-poor setting, is economical. Although the data presented here are not from randomized trials, several relevant observations have been made that could influence future, more structured assessments of the drug. An immune suppressive compound with antiviral features and experimental activity in chronic rejection is an attractive combination for organ transplantation, and it appears that leflunomide may just fit that niche. PMID- 22093815 TI - Association of pain with behavioral and psychiatric symptoms among nursing home residents with cognitive impairment: results from the SHELTER study. AB - The etiology of behavioral and psychiatric symptoms is generally considered to be multifactorial, and these symptoms often indicate a need for care or assistance, which may include the presence of uncontrolled pain. The aim of this cross sectional study was to assess the association of pain with behavioral and psychiatric symptoms in a population of nursing home (NH) residents with cognitive impairment in Europe. Data are from the SHELTER project, which contains information on NH residents in 8 countries. Pain was defined as any type of physical pain or discomfort in any part of the body in the 3 days before the assessment. The mean age of 2822 cognitively impaired residents entering the study was 84.1 (standard deviation 9.1)years, and 2110 (74.8%) were women. Of the total sample, 538 residents (19.1%) presented with pain. After adjusting for potential confounders, pain was significantly and positively associated with socially inappropriate behavior (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.04-1.80), resistance to care (OR 1.41; 95% CI 1.08-1.83), abnormal thought process (OR 1.48; 95% CI 1.16-1.90), and delusions (OR 1.48; 95% CI 1.07-2.03). A borderline inverse association was observed with wandering (OR 0.74; 95% CI 0.55 1.00). In conclusion, this cross-sectional study provides evidence from a large sample of frail elderly showing an association between pain and behavioral and psychiatric symptoms. Treatment models that put together assessment and treatment of pain and evaluate their effect on behavioral and psychiatric symptoms are needed. PMID- 22093816 TI - Pain-related avoidance versus endurance in primary care patients with subacute back pain: psychological characteristics and outcome at a 6-month follow-up. AB - Recent research has found individual differences in back pain patients due to behavioral avoidance vs persistence. However, there is a lack of prospective studies of nonspecific low back pain patients. The avoidance-endurance model (AEM) suggests at least 3 pathways leading to chronic pain: fear-avoidance response, distress-endurance response, and eustress-endurance response. We sought to compare these 3 maladaptive subgroups with an adaptive group using a classification tool that included the following scales: the thought suppression and behavioral endurance subscale of the Avoidance-Endurance Questionnaire and the Beck Depression Inventory. The psychological characteristics, and pain and disability of the AEM subgroups were investigated. We report results from 177 patients with subacute nonspecific low back pain at the start of outpatient treatment and at follow-up after 6 months. At baseline, a multivariate analysis of variance found that the fear-avoidance patients scored higher in pain catastrophizing than the other groups. The distress-endurance patients displayed elevated anxiety/depression and helplessness/hopelessness accompanied with the highest scores in the classification variables thought suppression and persistence behavior. The eustress-endurance patients had the highest humor/distraction scores, pain persistence, and positive mood despite pain. All 3 maladaptive groups revealed a higher pain intensity than the adaptive patients at follow-up after 6 months; however, disability at follow-up was elevated only in the fear-avoidance and distress-endurance patients. The study provides preliminary evidence for the construct and prospective validity of AEM-based subgroups of subacute, nonspecific back pain patients. The results suggest the need for individually targeted cognitive behavioral treatments in the maladaptive groups. PMID- 22093817 TI - Validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients. AB - Critically ill pediatric patients frequently receive prolonged analgesia and sedation to provide pain relief and facilitate intensive care therapies. Iatrogenic withdrawal syndrome occurs when these drugs are stopped abruptly or weaned too rapidly. We investigated the validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) in children during weaning of analgesics and sedatives. Of 308 children initially supported on mechanical ventilation for acute respiratory failure, 126 (41%) from 21 centers (median age 1.6 years; interquartile range 0.6-7.7 years) were exposed to 5 or more days of opioids. Subjects were assessed for withdrawal symptoms with the WAT-1, an 11-item (12 point) scale, from the first day of weaning from analgesia/sedation until 72 h after the last opioid dose. A total of 836 daily WAT-1 assessments were completed, with a median (interquartile range) WAT-1 score of 2 (0-4) over 6 (3 9) days per subject. There were no significant differences in WAT-1 scores as a function of age. Factor analyses confirmed that motor-related symptoms and behavioral state accounted for the most variance in WAT-1 scores. Supporting construct validity, cumulative opioid exposures were greater [40.2 (19.7-83.4) vs 17.6 (14.6-39.7) mg/kg, P=.004], length of opioid treatment before weaning was longer [7 (6-11) vs 5 (5-8)days, P=.004], and length of weaning from opioids was longer [10 (6-14) vs 6 (3-9)days, P=.008] in subjects with WAT-1 scores of >= 3 compared to subjects with WAT-1 scores of <3. The WAT-1 shows good psychometric performance and generalizability when used to assess clinically important withdrawal symptoms in pediatric intensive care and general ward settings. PMID- 22093818 TI - A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study. AB - BACKGROUND: Neuropeptide Y (NPY) is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue (AT). Acipimox (Aci) inhibits lipolysis in AT and reduces plasma glycerol and free fatty acid (FFA) levels. Exercise and Aci are enhancers of growth hormone (GH) and NPY secretion and exercise may alter leptin levels. We expect to find abnormal neuropeptidergic response in plasma and AT in patients with bulimia nervosa (BN). We hypothesize that Aci influences these peptides via a FFA-independent mechanism and that Aci inhibits lipolysis through a cyclic adenosine monophosphate (cAMP)-dependent pathway. Dysregulations of the AT-brain axis peptides might be involved in binge eating as is the case in BN. METHODS: The objective of this study was to determine the responses of plasma NPY, GH, leptin, FFA and glycerol levels to exercise in BN patients and healthy women (C) given the anti-lipolytic drug Aci or placebo. The secondary objective of this study was to compare the responses of extracellular glycerol levels and plasma glycerol levels to exercise alone or together with Aci administration in BN patients and C women. Extracellular glycerol was measured in vivo in subcutaneous (sc) abdominal AT using microdialysis. Eight BN and eight C women were recruited for this single-blind, randomized study. Aci or placebo was given 1 hour before the exercise (45 min, 2 W/kg of lean body mass [LBM]). NPY, GH, leptin, FFA, glycerol plasma and AT glycerol levels were measured using commercial kits. RESULTS: The primary outcome of this study was that the exercise with Aci administration resulted in plasma NPY and GH increase (after a 45-minute exercise) and leptin (after a 90-minute post-exercise recovering phase) increased more in BN patients. The secondary outcomes of this study were that the exercise with Aci administration induced a higher decrease of extracellular glycerol in BN patients compared to the C group, while the exercise induced a higher increase of glycerol concentrations in sc abdominal AT of BN patients. Plasma glycerol levels decreased more in BN patients and plasma FFA levels were depressed in both groups after the exercise with Aci administration. The exercise induced similar increases in plasma NPY, GH, FFA and glycerol levels, and a similar decrease in the plasma leptin level in both groups. CONCLUSIONS: We confirm the results of a single-blind, randomized, microdialysis study, i.e. that the Aci-induced elevation in plasma NPY and GH levels during the exercise is higher in BN patients and that Aci increased plasma leptin levels in the post-exercise recovering phase (90-minute) more in BN patients. The post-exercise rise (45 minute) in AT glycerol is much more attenuated by acute Aci treatment in BN patients. Simultaneously, we found facilitated turnover of plasma glycerol after the exercise together with Aci administration in BN. Our results support the hypotheses that Aci exerts an effect on the FFA-independent and cAMP-dependent mechanism. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000955910. PMID- 22093819 TI - Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion. AB - Human plasma membrane-associated sialidase (Neu3) is one of several sialidases that hydrolyze sialic acids in the terminal position of the carbohydrate groups of glycolipids and glycoproteins. Neu3 is mainly localized in plasma membranes and plays crucial roles in the regulation of cell surface functions. In this study, we investigated the effects and molecular mechanisms of Neu3 on cell invasion and migration in vivo and in vitro. Initially, we found that the levels of Neu3 expression were higher in prostate cancer tissues and cell lines than in normal prostate tissues based on RT-PCR and Western blotting analyses. We then applied a Neu3 siRNA approach to block Neu3 signaling using PC-3M cells as model cells. Transwell invasion assays and wound assays showed significantly decreased invasion and migration potential in the Neu3 siRNA-transfected cells. RT-PCR and Western blotting analyses revealed that Neu3 knockdown decreased the expressions of the matrix metalloproteinases MMP-2 and MMP-9. In vivo, mice injected with PC 3M cell tumors were evaluated by SPECT/CT to determine the presence of bone metastases. Mice treated with attenuated Salmonella carrying the Neu3 siRNA developed fewer bone metastases than mice treated with attenuated Salmonella carrying a control Scramble siRNA, attenuated Salmonella alone or PBS. The results for bone metastasis detection by pathology were consistent with the data obtained by SPECT/CT. Tumor blocks were evaluated by histochemical, RT-PCR and Western blotting analyses. The results revealed decreased expressions of MMP-2 and MMP-9 at the mRNA and protein levels. Taken together, the present findings suggest that Neu3 is a promising molecular target for the prevention of prostate cancer metastasis. PMID- 22093820 TI - Expression and characterization of recombinant kurtoxin, an inhibitor of T-type voltage-gated calcium channels. AB - Kurtoxin, a 63-amino acid peptide stabilized by four disulfide bonds, is the first reported peptide inhibitor of T-type voltage-gated calcium channels. Although T-type calcium channels have been implicated in a number of disease states, including epilepsy, chronic pain, hypertension and cancer, the lack of selective inhibitors has slowed progress in understanding their precise roles. Kurtoxin is a potentially valuable tool with which to study T-type calcium channels. However, because of the limited availability of the native protein, little is known about the structure and molecular mechanism of kurtoxin. Here we report the expression of kurtoxin in Escherichia coli and the structural and functional characterization of the recombinant protein. The disulfide bond pairings and secondary structure of recombinant kurtoxin were characterized through enzymatic cleavage, mass analysis and CD spectroscopy. Recombinant kurtoxin almost completely inhibited the T-type calcium channel in a manner identical to the native toxin. The availability of recombinant kurtoxin that is identical to the native toxin should help in the study of T-type calcium channels and enable development of new strategies for producing even more-selective T-type calcium channel inhibitors and for investigating the molecular basis of the toxin channel interactions. PMID- 22093821 TI - Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection. AB - Host tropism of hepatitis C virus (HCV) is limited to human and chimpanzee. HCV infection has never been fully understood because there are few conventional models for HCV infection. Human induced pluripotent stem cell-derived hepatocyte like (iPS-Hep) cells have been expected to use for drug discovery to predict therapeutic activities and side effects of compounds during the drug discovery process. However, the suitability of iPS-Hep cells as an experimental model for HCV research is not known. Here, we investigated the entry and genomic replication of HCV in iPS-Hep cells by using HCV pseudotype virus (HCVpv) and HCV subgenomic replicons, respectively. We showed that iPS-Hep cells, but not iPS cells, were susceptible to infection with HCVpv. The iPS-Hep cells expressed HCV receptors, including CD81, scavenger receptor class B type I (SR-BI), claudin-1, and occludin; in contrast, the iPS cells showed no expression of SR-BI or claudin 1. HCV RNA genome replication occurred in the iPS-Hep cells. Anti-CD81 antibody, an inhibitor of HCV entry, and interferon, an inhibitor of HCV genomic replication, dose-dependently attenuated HCVpv entry and HCV subgenomic replication in iPS-Hep cells, respectively. These findings suggest that iPS-Hep cells are an appropriate model for HCV infection. PMID- 22093822 TI - Preparation and characterization of cobalt-substituted anthrax lethal factor. AB - Anthrax lethal factor (LF) is a zinc-dependent endopeptidase involved in the cleavage of mitogen-activated protein kinase kinases near their N-termini. The current report concerns the preparation of cobalt-substituted LF (CoLF) and its characterization by electronic spectroscopy. Two strategies to produce CoLF were explored, including (i) a bio-assimilation approach involving the cultivation of LF-expressing Bacillus megaterium cells in the presence of CoCl(2), and (ii) direct exchange by treatment of zinc-LF with CoCl(2). Independent of the method employed, the protein was found to contain one Co(2+) per LF molecule, and was shown to be twice as active as its native zinc counterpart. The electronic spectrum of CoLF suggests the Co(2+) ion to be five-coordinate, an observation similar to that reported for other Co(2+)-substituted gluzincins, but distinct from that documented for the crystal structure of native LF. Furthermore, spectroscopic studies following the exposure of CoLF to thioglycolic acid (TGA) revealed a sequential mechanism of metal removal from LF, which likely involves the formation of an enzyme: Co(2+):TGA ternary complex prior to demetallation of the active site. CoLF reported herein constitutes the first spectroscopic probe of LF's active site, which may be utilized in future studies to gain further insight into the enzyme's mechanism and inhibitor interactions. PMID- 22093823 TI - Mode of ATM-dependent suppression of chromosome translocation. AB - It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double strand break repair pathway that requires kinase activity of DNA-PKcs. PMID- 22093824 TI - 5'-AMP-activated protein kinase (AMPK) regulates progesterone receptor transcriptional activity in breast cancer cells. AB - The steroid hormone progesterone is an essential regulator of the cellular processes that are required for the development and maintenance of reproductive function. The diverse effects of progesterone are mediated by the progesterone receptor (PR). The functions of the PR are regulated not only by ligands but also by modulators of various cell signaling pathways. However, it is not clear which energy state regulates PR activity. AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, is a key modulator of energy homeostasis. Once activated by an increasing cellular AMP:ATP ratio, AMPK switches off ATP consuming processes and switches on ATP-producing processes. We found that both 5 aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR) and metformin, traditional pharmacological activators of AMPK, inhibited the PR pathway, as evidenced by progesterone response element (PRE)-driven luciferase activity and PR target gene expression. Compound C, an inhibitor of AMPK, partly but significantly reversed the anti-PR effects of AICAR and metformin. The downregulation of endogenous AMPK by small interfering RNAs (siRNAs) stimulated PR activity. AMPK activation by AICAR decreased the progesterone-induced phosphorylation of PR at serine 294 and inhibited the recruitment of PR to an endogenous PRE. Taken together, our data suggest that AMPK, an energy sensor, is involved in the regulation of PR signaling. PMID- 22093825 TI - Expression of the prion-like protein Shadoo in the developing mouse embryo. AB - The prion-like protein Shadoo has been suggested to compensate for the lack of PrP in Prnp-knockout mice, explaining their lack of extreme phenotype. In adult mice, both PrP and Shadoo have shown overlapping expression patterns and shared functions. Their expression in the mouse embryo has also been suggested to be complementary, as invalidation of both genes results in embryonic lethality. The developmental expression profile of PrP has been described from post-implantation stages up until birth. However the spatial expression pattern of Shadoo in the developing mouse embryo is not known. We previously described the expression profile of the prion-like protein Shadoo in adult mice using Sprn reporter mice (Sprn-GFP and Sprn-LacZ). Here we used these mice to describe the developmental expression of Shadoo between 10.5 and 14.5 dpc. The observed pattern in specific embryonic cell lineages and in extra-embryonic tissues is consistent with the previously reported phenotype resulting from its knockdown. PMID- 22093826 TI - Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation. AB - Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression of BMP11 propeptide cDNA. The mice showed a transformation of the seventh cervical vertebra into a thoracic vertebra in our previous report. Presently, further characterizations of the transgenic mice indicated that ossification in calvatia was dramatically enhanced in transgenic fetuses at 16.5 dpc in comparison with their wild-type littermates. At 10 weeks of age, bone mineral content and bone mineral density were significantly (P<0.05) higher in transgenic mice than that in their wild-type littermates based on dual energy X-ray absorptiometry analysis. The relative trabecular bone volume measured by histological analysis was dramatically increased in transgenic mice compared with their wild-type littermates. The enhanced bone formations in the transgenic mice appear to result from increase osteoblast activities as the expressions of four osteoblast markers - alpha1 type 1 collagen, osteocalcin, alkaline phosphatase and phex were significantly higher in transgenic fetuses than that in their wild-type littermates. These results suggest that over-expression of BMP11 propeptide stimulates bone formation by increasing osteoblast cell functions. PMID- 22093827 TI - Involvement of leucine zipper transcription factor-like protein 1 (Lztfl1) in the attenuation of cognitive impairment by exercise training. AB - It is well known that exercise prevents and reduces cognitive impairment. In the present study, we focused on exercise training as a tool to prevent cognitive impairment, and searched for novel molecules that may relate to the prevention of cognitive impairment in the hippocampus. Two-month-old senescence-accelerated mouse prone-8 (SAMP8) mice were subjected to voluntary exercise training by running on a wheel for 4 months, and were then assigned a conditioned fear memory test. Moreover, various mRNA levels in the hippocampus were examined by DNA array analysis and real-time PCR. Contextual fear memory in SAMP8 control mice was significantly impaired compared with that in non-senescence mice. Exercise training definitely attenuated such cognitive impairment. The results of real time PCR analysis that was conducted following DNA array analysis in the hippocampus revealed that, compared with SAMR8 control mice, the expression levels of leucine zipper transcription factor-like protein 1 (Lztfl1) mRNA were significantly higher in SAMP8 mice subjected to exercise training. In addition, the overexpression of Lztfl1 promoted neurite outgrowth in Neuro 2a cells. These results suggest that exercise has a preventive effect on cognitive impairment in SAMP8 mice, and that exercise-induced increase in Lztfl1 induces neurite outgrowth. PMID- 22093828 TI - Characterisation and comparison of the chicken H1 RNA polymerase III promoter for short hairpin RNA expression. AB - The U6 and 7SK RNA polymerase III promoters are widely used in RNAi research for the expression of shRNAs. However, with their increasing use in vitro and in vivo, issues associated with cytotoxicity have become apparent with their use. Therefore, alternative promoters such as the weaker H1 promoter are becoming a popular choice. With interest in the chicken as a model organism, we aimed to identify and characterise the chicken H1 promoter for the expression of shRNAs for the purpose of RNAi. The chicken H1 promoter was isolated and sequence analysis identified conserved RNA polymerase III promoter elements. A shRNA expression cassette containing the chicken H1 promoter and shRNA targeting enhanced green fluorescent protein (EGFP) was developed. An RNAse protection assay confirmed activity of the promoter determined by the detection of expressed shRNAs. Comparison of the H1 promoter to the chicken RNA polymerase III 7SK and U6 promoters demonstrated that expressed shRNAs from the H1 promoter induced gene specific silencing, albeit to lower levels in comparison to both 7SK and U6 promoters. Here we have identified a new tool for RNAi research with specific applications to the chicken. The availability of a RNA polymerase III promoter that drives shRNA expression to reduced levels will greatly benefit in ovo/in vivo applications where there are concerns of cytotoxicity resulting from overexpression of an shRNA. PMID- 22093829 TI - Crystal structure and thermostability of a putative alpha-glucosidase from Thermotoga neapolitana. AB - Glycoside hydrolase family 4 (GH4) represents an unusual group of glucosidases with a requirement for NAD(+), Mn(2+), and reducing conditions. We found a putative alpha-glucosidase belonging to GH4 in hyperthermophilic Gram-negative bacterium Thermotoga neapolitana. In this study, we recombinantly expressed the putative alpha-glycosidase from T. neapolitana, and determined the crystal structure of the protein at a resolution of 2.0A in the presence of Mn(2+) but in the absence of NAD(+). The structure showed the dimeric assembly and the Mn(2+) coordination that other GH4 enzymes share. In comparison, we observed structural changes in T. neapolitana alpha-glucosidase by the binding of NAD(+), which also increased the thermostability. Numerous arginine-mediated salt-bridges were observed in the structure, and we confirmed that the salt bridges correlated with the thermostability of the proteins. Disruption of the salt bridge that linked N terminal and C-terminal parts at the surface dramatically decreased the thermostability. A mutation that changed the internal salt bridge to a hydrogen bond also decreased the thermostability of the protein. This study will help us to understand the function of the putative glucosidase and the structural features that affect the thermostability of the protein. PMID- 22093830 TI - Gold nanoparticle-assisted delivery of small, highly structured RNA into the nuclei of human cells. AB - Previous studies have shown that functionalized gold nanoparticles (AuNPs) can be used as a general platform for loading and delivering DNA oligonucleotides and short hairpin RNA to living systems. Here, we report the ability of functionalized AuNP to deliver RNA aptamers into the nuclei of human cells. An in vitro-synthesized RNA aptamer specific to the beta-catenin protein was delivered into the HepG2 human cell line more efficiently via functionalized AuNP than liposome-based delivery, and resulted in nearly complete inhibition of beta catenin binding to the p50 subunit of NF-kappaB in the nucleus. This inhibition led to repression of NF-kappaB p50-dependent transcription of CRP. Also, the beta catenin aptamer in the nucleus led to down-regulation of beta-catenin-mediated transcriptional activity through the TCF complex and resulted in decrease in the levels of cyclin D, and c-myc mRNA by ~47% and ~57%, respectively. In addition, we used functionalized AuNP to deliver another RNA aptamer targeted to the p50 subunit of NF-kappaB into the A549 human cell line, and this was sufficient to induce apoptosis of the cells. Our findings demonstrate that AuNP GDS can be used to deliver small, highly structured RNA aptamers into the nucleus of human cells where they modulate the activity of transactivators by interacting with target proteins. PMID- 22093831 TI - Nkx3.2-induced suppression of Runx2 is a crucial mediator of hypoxia-dependent maintenance of chondrocyte phenotypes. AB - Hypoxia is a key factor in the maintenance of chondrocyte identity. However, crucial chondrogenic transcription factors in the Sox families are not activated in this phenomenon, indicating that other pathways are involved. Nkx3.2 is a well known chondrogenic transcription factor induced by Sonic hedgehog (Shh); it suppresses a key osteogenic transcriptional factor, Runt-related transcription factor 2 (Runx2), to maintain the chondrogenic phenotype in mesenchymal lineages. The purpose of this study was to examine the function of Nkx3.2 in hypoxia dependent maintenance of chondrocyte identity. C3H10T1/2 pluripotent mesenchymal cells were cultured with rh-BMP2 (300 ng/ml) to induce chondrogenesis under normoxic (20% O(2)) or hypoxic (5% O(2)) conditions. Immunohistological detection of Nkx3.2 in a micromass cell culture system revealed that hypoxia promoted expression of the Nkx3.2 protein. Real-time RT-PCR analysis revealed that hypoxia promoted Nkx3.2 mRNA expression and suppressed Runx2 mRNA expression; however, Sox9 mRNA expression was not altered by oxygen conditions, as previously described. Over-expression of exogenous Nkx3.2 promoted glycosaminoglycan (GAG) production and inhibited Runx2 mRNA expression and, based on a dual luciferase assay, Runx2 promoter activity. Interestingly, downregulation of Nkx3.2 using RNAi abolished hypoxia-dependent GAG production and restored Runx2 mRNA expression and promoter activity. These results demonstrated that Nkx3.2 dependent suppression of Runx2 was a crucial factor in hypoxia-dependent maintenance of chondrocyte identity. PMID- 22093832 TI - Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-alpha treated A549 cells. AB - Cyclooxygenase-2 (COX-2) over-expression is frequently associated with human non small-cell lung cancer (NSCLC) and involved in tumor proliferation, invasion, angiogenesis and resistance to apoptosis. In the present study, the effects of triptolide on COX-2 expression in A549 cells were investigated and triptolide was found to inhibit TNF-alpha-induced COX-2 expression. In our further studies, it was found that triptolide decreased the half-life of COX-2 mRNA dramatically and that it inhibited 3'-untranslated region (3'-UTR) fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased COX-2 mRNA in pull-down experiments with anti-HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased COX-2 mRNA. Taken together, our results provided evidence for the first time that triptolide inhibited COX-2 expression by COX-2 mRNA stability modulation and post-transcriptional regulation. These results provide a novel mechanism of action for triptolide which may be important in the treatment of lung cancer. PMID- 22093833 TI - Role of suppressor of cytokine signaling 3 in lipid metabolism: analysis based on a phage-display human liver cDNA library. AB - Suppressor of cytokine signaling 3 (SOCS3) is a likely mediator of feedback inhibition on the leptin receptor and may cause physiological leptin-resistance, leading to the development of obesity. The aim of this study was to identify potential peptides interacting with purified SOCS3 by using a phage-display human liver cDNA library. We developed a T7 select phage-display system with purified SOCS3 as bait to screen a human liver cDNA library. After 4 rounds of screening and sequencing analysis, we found that phage-presenting peptide RGGVVTSNPLGF show significant binding to SOCS3. The peptide sequence was similar to the sequence of amino acids 644-655 of C-terminal extra-polypeptide of very-long-chain acyl-CoA dehydrogenase (VLCAD), which is 1 of 4 flavoproteins that catalyzing the initial step of the mitochondrial fatty acid beta-oxidation, implying a close relationship between SOCS3 and VLCAD. We identified VLCAD as a novel SOCS3 interacting protein both in vitro and vivo, and found that SOCS3 mediates the ubiquitination pathway for proteasomal degradation of VLCAD C-terminal extra polypeptide via its SOCS-box. Animal experimentation demonstrated that VLCAD is functionally involved in SOCS3 binding and thus, SOCS3 play an important role in the regulation of fatty acid beta-oxidation. In conclusion, SOCS3 is an important factor for lipid metabolism and a potential drug-target for treatment of widespread obesity. PMID- 22093834 TI - miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3. AB - There is accumulating evidence that microRNAs are involved in multiple processes in development and tumor progression. Abnormally expressed miR-125b was found to play a fundamental role in several types of cancer; however, whether miR-125b participates in regulating the initiation and progress of osteosarcoma still remains unclear. Here we demonstrate that miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. The ectopic restoration of miR-125b expression in human osteosarcoma cells suppresses proliferation and migration in vitro and inhibits tumor formation in vivo. We further identified signal transducer and activator of transcription 3 (STAT3) as the direct and functional downstream target of miR-125b. Interestingly, we discovered that the expression of miR-125b is regulated by STAT3 at the level of transcription. STAT3 binds to the promoter region of miR-125b in vitro and serves as a transactivator. Taken together, our findings point to an important role in the molecular etiology of osteosarcoma and suggest that miR-125b is a potential target in the treatment of osteosarcoma. PMID- 22093835 TI - Evaluation of a UCMK/dCK fusion enzyme for gemcitabine-mediated cytotoxicity. AB - While gemcitabine (2'-2'-difluoro-2'-deoxycytidine, dFdC) displays wide-ranging antineoplastic activity as a single agent, variable response rates and poor intracellular metabolism often limit its clinical efficacy. In an effort to enhance dFdC cytotoxicity and help normalize response rates, we created a bifunctional fusion enzyme that combines the enzymatic activities of deoxycytidine kinase (dCK) and uridine/cytidine monophosphate kinase (UCMK) in a single polypeptide. Our goal was to evaluate whether the created fusion could induce beneficial, functional changes toward dFdC, expedite dFdC conversion to its active antimetabolites and consequently amplify cell dFdC sensitivity. While kinetic analyses revealed the UCMK/dCK fusion enzyme to possess both native activities, the fusion rendered cells sensitive to the cytotoxic effects of dFdC at the same level as dCK expression alone. These results suggest that increased wild-type UCMK expression does not provide a significant enhancement in dFdC mediated cytotoxicity and may warrant the implementation of studies aimed at engineering UCMK variants with improved activity toward gemcitabine monophosphate. PMID- 22093836 TI - A structural model of the HIV-1 Rev-integrase complex: the molecular basis of integrase regulation by Rev. AB - The HIV-1 Rev and integrase (IN) proteins control important functions in the viral life cycle. We have recently discovered that the interaction between these proteins results in inhibition of IN enzymatic activity. Peptides derived from the Rev and IN binding interfaces have a profound effect on IN catalytic activity: Peptides derived from Rev inhibit IN, while peptides derived from IN stimulate IN activity by inhibiting the Rev-IN interaction. This inhibition leads to multi integration, genomic instability and specific death of virus-infected cells. Here we used protein docking combined with refinement and energy function ranking to suggest a structural model for the Rev-IN complex. Our results indicate that a Rev monomer binds IN at two sites that match our experimental binding data: (1) IN residues 66-80 and 118-128; (2) IN residues 174-188. According to our model, IN binds Rev and its cellular cofactor, lens epithelium derived growth factor (LEDGF), through overlapping interfaces. This supports previous observations that IN is regulated by a tight interplay between Rev and LEDGF. Rev may bind either the IN dimer or tetramer. Accordingly, Rev is suggested to inhibit IN by two possible mechanisms: (i) shifting the oligomerization equilibrium of IN from an active dimer to an inactive tetramer; (ii) displacing LEDGF from IN, resulting in inhibition of IN binding to the viral DNA. Our model is expected to contribute to the development of lead compounds that inhibit the Rev-IN interaction and thus lead to multi-integration of viral cDNA and consequently to apoptosis of HIV-1 infected cells. PMID- 22093837 TI - Novel multi-component enzyme machinery in lactic acid bacteria catalyzing C=C double bond migration useful for conjugated fatty acid synthesis. AB - Linoleic acid isomerase was identified as a multi-component enzyme system that consists of three enzymes that exist in both the membrane and soluble fractions of Lactobacillus plantarum. One enzyme (CLA-HY) is present in the membrane fraction, while two enzymes (CLA-DH and CLA-DC) exist in the soluble fraction. Three Escherichia coli transformants expressing CLA-HY, CLA-DH, and CLA-DC were constructed. Conjugated linoleic acid (CLA) and 10-hydroxy-12-octadecenoic acid were generated from linoleic acid only when all these three E. coli transformants were used as catalysts simultaneously. CLA-HY catalyzed the hydration reaction, a part of linoleic acid isomerization, to produce 10-hydroxy-12-octadecenoic acid. This multi-component enzyme system required oxidoreduction cofactors such as NADH and FAD. This is the first report to reveal enzymes genes and the elaborate machinery that synthesizes CLA, especially an important isomer of cis-9, trans-11 CLA, in lactic acid bacteria. PMID- 22093838 TI - [Norepinephrine-new milestone for treatment of shock]. PMID- 22093839 TI - [Effects of statins on mortality in patients with infection: a systematic review]. AB - OBJECTIVE: To review systematically the literatures regarding the effect of statins on mortality in patients with infection. METHODS: PUBMED, EMBASE, Web of Science and CNKI databases from 2000 to 2010 were searched. And the clinical trials on statins-related mortality in patients with infection were identified by electronic and manual searching. A systematic review of relevant data was conducted by the methods as recommended by the Cochrane Collaboration. RESULTS: Sixteen trials (11 retrospective and 5 prospective cohort studies) involving 8775 cases in statins group and 46 539 in control group were included for analysis. The mortalities of infection were 5.2% (458/8775) and 18.6% (8637/46 539) in statins and control groups respectively. In comparison with control group, statins could reduce the mortality in patients with infection [OR = 0.51, (95% CI: 0.36 - 0.71); P < 0.000 01]. Prospective cohort studies observed 6774 patients with infection whose survival were improved by statins [OR = 0.48, (95% CI: 0.24 - 0.94); P = 0.03]. It was consistent with the results of retrospective cohort studies [OR = 0.66, (95% CI: 0.58 - 0.75); P = 0.002] and large sample studies [OR = 0.56, (95% CI: 0.50 - 0.63); P = 0.02]. Statins lowered the short term mortality [OR = 0.47, (95% CI: 0.29 - 0.78); P = 0.004], but failed to improve the outcomes of severe septic patients in Intensive Care Unit (ICU) [OR = 0.69, (95% CI: 0.32 - 1.48); P = 0.34]. CONCLUSION: Statins have favorable effects on the patients with infection, but there is no effect for severe septic patients in ICU. Further randomized controlled trials of a large sample size are warranted. PMID- 22093840 TI - [Impact of extended focus assessed transthoracic echocardiography protocol in septic shock patients]. AB - OBJECTIVE: To investigate the impact of extended focus assessed transthoracic echocardiography (eFATE) in septic shock patients. METHODS: A total of 83 septic shock patients were recruited. And they were divided into the eFATE and routine groups. In the routine group, the patients were assessed by routine methods. And in the eFATE group, the following parameters of central venous pressure (CVP), mean arterial pressure (MAP), cardiac index (CI), stroke volume index (SVI) and ScvO(2) (central venous oxygen saturation) were measured routinely. The PiCCO (pulse indicator continuous cardiac output) method was employed when needed. All parameters and the others [acute physiology and chronic health evaluation II (APACHEII) & lactate] were recorded every 6 h. At 6, 24, 72 h and 1 w, the fluid intake volumes were recorded. All values were analyzed by statistic methods. And the mortality rates of intensive care unit and Day 28 were recorded. RESULTS: In the eFATE group, the 24 h targeting rate was markedly higher than the routine group. Yet there was no effect on the 6 h targeting rate. In the eFATE group, the fluid intake volumes at 6, 24 h and 1 w were markedly lowered than those of the control group. And the myocardial inhibition occurred earlier versus the control group. There was no difference in mortality rate between two groups. CONCLUSION: eFATE plays an important role in the correct assessment of septic shock patients. But its prognostic impact remains to be further defined. PMID- 22093841 TI - [Effects of mechanical ventilation and positive end-expiratory on central venous pressure]. AB - OBJECTIVE: To investigate the effects of mechanical ventilation and positive end expiratory pressure (PEEP) on central venous pressure (CVP). METHODS: Forty cases of respiratory failure with mechanical ventilation were enrolled. Catheter was inserted via subclavian vein in each. And then CVP was measured without mechanical ventilation and under different PEEP conditions of 0, 6 and 12 cm H2O. RESULTS: Mechanical ventilation could affect the levels of CVP, P(peak) ~ PS+PEEP, followed PEEP, t = 3.364, P = 0.006. There was significant difference was found among the three groups, F = 15.293, P = 0.000. And CVP increased with a rising level of PEEP. CONCLUSION: Mechanical ventilation and PEEP affect the accuracy of CVP. PMID- 22093842 TI - [Psychiatric comorbidities in patients referred for irritable bowel syndrome]. AB - OBJECTIVE: To assess the prevalence of psychiatric comorbidities in patients referred for irritable bowel syndrome (IBS) with questionnaires for mental disorders. METHODS: A total of 83 IBS patients at our hospital were enrolled and assessed with the Personality Diagnostic Questionnaire for DSM-IV, version 4 (PDQ 4) and Composite International Diagnostic Interview, version 3.0 and 2.1 (CIDI 3.0 & CIDI-2.1) by trained interviewers. Such items as personality dysfunction, mental disorder and somatization disorder were examined. RESULTS: The male-female ratio was 1.08/1. Their mean age was (38 +/- 14) years old. Among them, 20 patients (24.1%) were constipation-predominant, 31 (37.3%) diarrhea-predominant, 15 (18.1%) mixed and 17 (20.5%) unclassified type. (1) Sixty-two (74.7%) patients scored positive for any personality dysfunction. There was no significant gender difference. The cluster C (anxious-fearful) personality disorder was most commonly found in IBS patients (n = 58, 69.9%). The prevalence of somatoform disorders plus personality dysfunction was 46.8% (29/62). It was significantly higher than those without personality dysfunction [19.0% (4/21), P = 0.025]. (2) Thirty-seven patients (44.6%) had a lifetime CIDI-3.0 diagnosis. It was significantly higher than that in the general population. There was no gender difference. Anxiety and mood disorders were the most common types of psychiatric comorbidities [n = 21 (25.3%) and n = 19 (22.9%) respectively]. The lifetime prevalence of alcohol or nicotine abuse and(or) dependence and intermittent explosive disorder were 10.8% (n = 9) and 8.4% (n = 7). Psychiatric comorbidities were most commonly found in diarrhea-predominant patients (58.1%). But there was no significant difference among the subgroups. (3) Thirty-three patients (39.8%) had somatoform disorders. Neither gender nor subgroup difference was observed. The IBS patients with anxiety disorders presented significantly more somatoform disorders than the remainders [61.9% (13/21) vs 32.3% (20/62), P = 0.016]. CONCLUSION: Such psychiatric comorbidities as anxiety disorders and mood disorders are common in patients referred for IBS. The patients with personality dysfunction and(or) anxiety were more likely to suffer somatoform disorders. A gastroenterologist should grasp a thorough knowledge and make appropriate therapeutic recommendations for those patients. PMID- 22093843 TI - [Performance of current infection marker test for the diagnosis of Helicobacter pylori current infection: a multicenter clinical trial]. AB - OBJECTIVE: To evaluate the performance of the ASSURE(TM) Helicobacter pylori (H. pylori) rapid test [current infection marker (CIM) kit, Genelabs Diagnostics] in detecting the current infection marker CIM for the diagnosis of H. pylori in adult patients. METHODS: For this multicenter and controlled clinical trial, a total of 300 patients with an average age of (41 +/- 16) years old were recruited from 7 participating hospitals. There were 128 men and 172 women, never received any H. pylori eradication therapy. Each subject received a (13)C-urea breath test ((13)C-UBT) and a CIM test. Such performance parameters as sensitivity, specificity, positive and negative predictive values and accuracy were determined by (13)C-UBT for the diagnosis of current H. pylori infection. RESULTS: According to the gold standard, there were 131 positive and 169 negative subjects. The accuracy rate, sensitivity, specificity, positive and negative predictive values of CIM test were 89.0% (267/300), 87.8% (115/131), 89.9% (152/169), 87.1% (115/132) and 90.5% (152/168) respectively. CONCLUSION: As a simple, rapid, accurate and affordable assay, CIM test may be useful for a non-invasive diagnosis of H. pylori infection in cases without eradication therapy. PMID- 22093844 TI - [Value of peritoneoscopy via natural orifice transluminal endoscopic surgery in the diagnosis of peritoneal carcinomatosis]. AB - OBJECTIVE: To evaluate the value of peritoneoscopy via natural orifice transluminal endoscopic surgery (NOTES) in the diagnosis of patients with peritoneal carcinomatosis. METHODS: A total of 32 patients with peritoneal carcinomatosis were diagnosed by histological examination of biopsies at our hospital from April 2007 to October 2010. Their data of clinical manifestations, gastroscopy, colonoscopy, abdominal ultrasonography, abdominal computed tomography, magnetic resonance imaging, ascitic cytology and transgastric peritoneoscopy via NOTES were analyzed retrospectively. RESULTS: Among them, gastrointestinal cancers were diagnosed by digestive endoscopy in 9 cases (28.1%). And ovarian lesions in 8 cases (25.0%), pancreatic cancer in 2 cases (6.3%), primary liver cancer in 2 cases (6.3%) and bile duct carcinoma in 1 case (3.1%) were suspected according to imaging examinations. No peritoneal carcinomatosis was found by digestive endoscopy or imaging examinations. Ascitic cytology was positive in 6 cases (18.8%). Peritoneal carcinomatosis was diagnosed by transgastric peritoneoscopy via NOTES with histological examination of biopsies in all patients. Their findings of transgastric peritoneoscopy via NOTES were divided into 5 types, i.e., mass type (n = 3, 9.4%), nodular type (n = 5, 15.6%), ulcerative type (n = 1, 3.1%), omentum-embracing type (n = 1, 3.1%) and mixture type (n = 22, 68.8%). CONCLUSION: Transgastric peritoneoscopy via NOTES with histological examination of biopsies has important value in the pathologic diagnosis and the endoscopic typing of peritoneal carcinomatosis. PMID- 22093845 TI - [Age-related changes of normal adult inferior rectus muscle:analysis with dynamic contrast-enhanced magnetic resonance imaging]. AB - OBJECTIVE: To explore the age-related changes of blood supply and extracellular space volume in normal adult inferior rectus muscle, evaluate the microcirculation in extraocular muscle and offer important information for the diagnosis and treatment of extraocular muscle disorders. METHODS: A total of 250 patients undergoing nose-sinus dynamic contrast-enhanced magnetic resonance imaging were studied. Five groups were divided according to age (20 - 30 yr old, 30 - 40 yr old, 40 - 50 yr old, 50 - 60 yr old and over 60 yr old). The technique of 3DFSPGR (3-dimensional fast spoiled gradient-recalled) was used in dynamic contrast-enhanced imaging scanning 4 minutes and 59 seconds and acquiring 12 phases. Time-intensity curves of orbital layer, global layer of inferior rectus muscle and temporal muscle ipsilaterally were drawn on post-process work station. From the curves, the values of SIpre, SImax and SIphase12 were obtained and then SIpeak (peak signal intensity), Tpeak (time of peak enhancement) and WR (washout ratio) computed. The data were analyzed statistically. RESULTS: SIpeak of orbital layer in all groups was as follows: 404.7 +/- 12.7, 395.1 +/- 15.9, 367.3 +/- 5.1, 307.0 +/- 12.4 and 265.3 +/- 6.2 respectively. Tpeak: (85.2 +/- 1.0) s, (93.2 +/- 8.1) s, (106.8 +/- 4.6), (122.8 +/- 8.6) s and (133.0 +/- 0.8) s respectively. WR: (9.25 +/- 0.50)%, (8.25 +/- 0.50)%, (7.50 +/- 0.58)%, (4.75 +/- 1.26)% and (3.50 +/- 1.73)% respectively. SIpeak of global layer in all groups was as follows:261.9 +/- 2.1, 256.6 +/- 1.1, 243.8 +/- 3.3, 225.4 +/- 4.9 and 219.8 +/- 5.3 respectively. Tpeak: (157.8 +/- 1.7) s, (166.5 +/- 4.5) s, (173.2 +/- 7.2) s, (192.8 +/- 9.1) s and (200.5 +/- 2.4) s respectively. WR: (7.25 +/- 0.50)%, (6.27 +/- 0.00)%, (4.50 +/- 0.58)%, (3.75 +/- 0.50)% and (2.25 +/- 1.50)% respectively. SIpeak, Tpeak and WR of temporal muscle in all groups showed no statistical significance (P > 0.05). Tpeak increased while SIpeak and WR decreased with age. Furthermore the changes of Tpeak of orbital layer were more sensitive. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging can non-invasively reflect the age-related changes of blood supply and extracellular space volume in normal adult inferior rectus muscle so as to offer important information for the diagnosis and treatment of extraocular muscle disorders. PMID- 22093846 TI - [A comparison study on cognitive function in patients with single subcortical lesion stroke of four different areas]. AB - OBJECTIVE: Comparing the characteristics of cognitive impairment of patients with single subcortical lesion stroke of four different areas, we are to explore the cognitive function of the thalamus and basal ganglia and this is help for early identification of vascular cognitive impairment (VCI). METHODS: 63 patients with single subcortical lesion stroke (including 14 left thalamic stoke group, 17 left basal ganglia stroke group, 15 right thalamic stroke group, 17 right basal ganglia stroke group) and 34 healthy subjects participated in the current study, whose age, sex and education were matched. A comprehensive neuropsychological battery was used for evaluation. RESULTS: Compared to the normal control group, there was an overall decline of cognitive functions in patients with single subcortical lesion stroke in memory, attention/executive function, language, and visuospatial ability (P < 0.05). The scores of the left thalamic stroke group were worse than the other three stroke groups in language (BNT16.6 +/- 2.6), auditory verbal learning test-immediate recall (12.8 +/- 4.4), auditory verbal learning test-delayed recall (2.4 +/- 2.3), listening recognition (19.1 +/- 3.1), structure delayed recall (9.1 +/- 4.7) and symbol digit modalities test-recall (0.9 +/- 1.1) (P < 0.05). However, the left basal ganglia stroke group did better in tests manipulated by the right hand [including Trial making test (part A) score (75 +/- 22), Trail making test (part B) score (204 +/- 81), Clock drawing test (23.5 +/- 4.6), Symbol digit modalities test (24 +/- 9)] than other three stroke group, as good as the normal group (P < 0.05). CONCLUSIONS: Single subcortical stroke patients may have general, non-selective cognitive impairment. But, different stroke areas have their own characteristics. The scores of the left thalamic stroke group were worse than the other three stroke groups. PMID- 22093847 TI - [Evaluation of safety and anesthetic effect for ultrasound-guided cervical plexus block]. AB - OBJECTIVE: To observe the influences upon the degree of diaphragmatic excursion during deep cervical plexus block at the third cervical vertebra (C3) and compare the safety and anesthetic effect of modified cervical plexus block by ultrasonic guidance and blocking of cervical plexus at one point. METHODS: Part I: 30 patients of ASA (American society of anesthesiologists) I-II scheduled for thyroid surgery were selected for bilateral cervical plexus block at C3 and bilateral skin nerve branches via ultrasonic guidance. Diaphragmatic excursion was recorded. Part II: 80 patients of ASAI-II scheduled for thyroid surgery were randomly divided into 2 groups: experimental group (Group U) and control group (Group C). In Group U, modified cervical plexus block was used to fix both sides of C3 and skin nerve branches. The anesthetic mixture with 2% lidocaine and 0.75% ropivacaine was injected. And anesthetic effects and complications were detected. In control group, traditional one-point method for blocking cervical plexus was employed. RESULTS: High-frequency Doppler sonography could clearly visualize important neck structures and precisely guide the injection of mixture to the transverse process of C3. Diaphragmatic excursion decreased significantly at 15 and 30 min post-blocking (P < 0.05). And no paralysis of diaphragmatic muscle occurred. Hoverer 3 cases had partial diaphragmatic paralysis. Both blood pressure and heart rate increased significantly post-blocking in both groups (P < 0.05 or 0.01). In comparison with Group C, the range of blood pressure was notably lower at 10 and 20 min in Group U. And heart rate was notably lower at 5, 10, 20 and 30 min (P < 0.05 or 0.01). Furthermore the onset time of skin nerve branches was significantly shorter in Group U (P < 0.01). And the anesthetic effect score was better than that in Group C (P < 0.01). The incidence of complications, such as hoarseness, was significantly lower in Group U (12 cases in Group C but none in Group U, P < 0.01) and Horner's syndrome (2 cases in Group C). The number of cases requiring hypotensor and heart rate control drug was significantly smaller in Group U than that in Group C (P < 0.01). CONCLUSION: The improving effect of ultrasound-guided cervical plexus block upon the degree of diaphragmatic movement is within the compensatory range of body. In comparison with the traditional one-point blocking of cervical plexus, the modified cervical plexus block with ultrasonic guidance offers better anesthetic effects, fewer complications and convenient anesthetic localization. Thus it may be clinically applicable. PMID- 22093848 TI - [Neuroendoscope-assisted surgical treatment of spinal dural arteriovenous fistulas]. AB - OBJECTIVE: To study the utility of neuroendoscope-assisted surgery in the treatment of spinal dural arteriovenous fistulas. METHODS: From November 2008 to November 2010, 8 cases of spinal dural arteriovenous fistulas underwent neuroendoscope-assisted surgical treatment by a hemilaminectomy approach. Retrospective analyses were performed for their clinical manifestations, imaging findings, surgical approaches, postoperative recovery and follow-up profiles. RESULTS: All were of single fistula. Under the assistance of neuroendoscope, the fistulas were found intra-operatively and the draining veins disconnected successfully. The results of post-operative angiography showed the disappearance of all draining veins. After a follow-up period of 3 - 35 months, 2 cases became asymptomatic, 5 cases improved obviously and 1 case had no change. CONCLUSION: Neuroendoscope-assisted surgery is mini-invasive, safe and effective in the treatment of spinal dural arteriovenous fistulas. PMID- 22093849 TI - [Value of bronchoalveolar lavage as a rescue measurement for systemic lupus erythematosus complicated with diffuse alveolar hemorrhage]. AB - OBJECTIVE: To explore the value of bronchoalveolar lavage as an emergency treatment for systemic lupus erythematosus (SLE) patients with concurrent diffuse alveolar hemorrhage (DAH). METHODS: A total of 21 SLE plus DAH patients were divided randomly into 2 groups. The patients in Group A received methylprednisolone 1000 mg/d for 3 days while those in Group B methylprednisolone 1000 mg/d for 3 days in combination with a bronchoalveolar lavage. Partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), oxygen saturation (SaO2) and Borg scale (BS) for quantitative evaluation of dyspnea were recorded before and after treatment. RESULTS: Except for PaCO2, all other parameters of blood gas analysis in all patients in Group A (P > 0.05) were better after treatment than before (all P < 0.05). After treatment, PaO2 and SaO2 in Group B were higher than those in Group A (all P < 0.05), but PaCO2 was not markedly changed (P > 0.05). BS decreased significantly in both groups (both P < 0.01). And more decrease was observed in Group B as compared with Group A after treatment (P < 0.05). CONCLUSION: Bronchoalveolar lavage plus a high-dose implosive therapy of methylprednisolone may alleviate hypoxemia and dyspnea in acute period of SLE complicated with DAH. PMID- 22093850 TI - [Prevention of peri-operative infection with sequential therapy of levofloxacin in patients undergoing laparoscopic hysterectomy, laparoscopic assisted vaginal hysterectomy and transvaginal hysterectomy]. AB - OBJECTIVE: To investigate the effect and safety of sequential therapy of levofloxacin in the prevention of peri-operative infections among patients undergoing laparoscopic hysterectomy (LH), laparoscopic assisted vaginal hysterectomy (LAVH) and transvaginal hysterectomy (TVH). METHODS: During 2009 - 2010, a total of 50 patients with the indications for LH, LAVH or TVH at our hospital were recruited. Their age range was 18 - 65 years old. In fair general conditions, they had no severe infection of female reproductive system. Levofloxacin 500 mg was administered by an intravenous injection once daily and then orally once daily. RESULTS: The average duration of intravenous injection of levofloxacin was 4.3 days while and the duration of its oral administration 4.5 days. No infection was seen in 48 patients with an efficient prevention rate of 96.0%. Only 1 patient showed mild gastroenterological reactions. The side reaction rate was 2.0%. CONCLUSION: The sequential therapy of levofloxacin is both effective and safe in the prevention of peri-operative infections among patients undergoing LH, LAVH and TVH. PMID- 22093851 TI - [Evaluating radiation dose of 128-slice dual-source computed tomographic coronary angiography with different electrocardiogram pulsing models]. AB - OBJECTIVE: To determine the effects of heart rate frequency (HRF) and heart rate variability (HRV) on radiation exposure and image quality in a large cohort of patients undergoing DSCT (dual-source computed tomograph) coronary angiography with three different electrocardiogram (ECG) pulsing models, to prospectively investigate CT image quality parameters by using different protocols and to calculate the radiation dose estimates for noninvasive coronary angiography performed by DSCT. METHODS: Over a 1-month period, 253 consecutive patients were recruited and categorized into 3 groups: Group A:low HRF (<= 75 beats/min) with normal-minor heart rate variability (HRV) (mean interbeat difference (IBD), 0 - 3), coronary CT angiography proceeding with prospective ECG-triggered flash spiral scan; Group B: intermediate-high HRF (> 75 beats/min) with normal-minor HRV (IBD, 0 - 4), with prospective ECG-triggered sequence scan; Group C: intermediate-high HRF (> 75 beats/min) with moderate-severe HRV (IBD >= 5) with retrospective ECG-gated spiral scan. RESULTS: CT coronary angiography yielded excellent image quality in 87.7% of patients (222/253). No significant differences were found among three groups with different HRF and HRV in image quality and diagnostic performance. Radiation exposure was significantly higher in patients with low versus high HRF and in patients with severe versus normal HRV. Significant difference (P < 0.001) was found among the effective doses of group A (mean +/- standard deviation, 0.602 +/- 0.363 mSv), group B (1.253 +/- 0.804 mSv) and group C (9.039 +/- 5.657 mSv). CONCLUSION: The higher temporal resolution of dual-source spiral CT coronary angiography performed with adaptive ECG pulsing results in preserved diagnostic image quality and performance independent of HRF or HRV at the cost of limited dose reduction in arrhythmic patients. PMID- 22093852 TI - [Study on thoracoabdominal incision for thoracic esophageal carcinoma by rotation position]. AB - OBJECTIVE: To explore the clinical feasibility of thoracoabdominal incision for thoracic esophageal carcinoma by rotation position. METHODS: From January 2004 to December 2007, 126 patients with thoracic esophageal carcinoma performed operation by rotation position. There were 75 males and 51 females aged 46 to 78 years. Tumor was located mid-esophagus in 74 patients, whereas sub-esophagus was present in 52 patients. All patients underwent esophagectomy by rotation position (thoracoabdominal incision). Thoracic and abdominal cavity were exposed well. RESULTS: All operations were completed successful. Anastomotic stoma was located right thorax. The mean number of tow-field lymph node dissection was 25.6. There was no mortality. Postoperative complication include pulmonary complication, incision infection, recurrent laryngeal nerve damage, arrhythmia. The operation time was significantly shortened by rotation position. The number of lymph node dissection was significantly increased. CONCLUSION: The results of this study demonstrated that thoracoabdominal incision for thoracic esophageal carcinoma by rotation position exposes the operation fields clearly and make radical lymphadenectomy thoroughly. Disease-free survival is significantly improved. PMID- 22093853 TI - [Diagnosis and surgical treatment for mediastinal hemangioma and lymphangioma]. AB - OBJECTIVE: To review the experience of diagnosis and surgical treatment of the primary mediastinal hemangioma and lymphangioma. METHODS: We summarized the medical records of patients with primary mediastinal hemangioma or lymphangioma at our hospital from January 1998 to January 2009, then extracted relevant clinical data and carried out the retrospective analysis. RESULTS: There were 11 patients in the whole group. The age range was 4 - 78 years old (average: 38.9). Six patients were symptom-free and most patients had not an accurate preoperative diagnosis. All patients underwent surgical procedures. The radical excision was accomplished in 10 cases and incomplete excision in 1 case. Two cases of surgically related complications were observed. All the cases were diagnosed by postoperative histopathological examination. There were hemangioma (n = 5), lymphangioma (n = 3) and hematolymphangioma (n = 3). CONCLUSIONS: The operation should be performed once the diagnosis of hemangioma or lymphangioma is made. Radical excision should be performed to prevent a post-operative recurrence. PMID- 22093855 TI - Diabetes and insulin resistance in pediatric obesity. AB - Over the past 2 decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM) in children and adolescents has risen to epidemic proportions and disproportionately affects racial and ethnic minorities, who are at greater risk. The pathophysiology of T2DM is complex and involves insulin resistance, pancreatic beta-cell dysfunction, and visceral adiposity. Current treatments of T2DM are limited to lifestyle intervention, metformin, and insulin therapy; use of these strategies in combination is often most effective. The role of research is to uncover simple biomarkers for insulin sensitivity and optimal and innovative treatment of insulin resistance and T2DM. PMID- 22093854 TI - Etiologies of obesity in children: nature and nurture. AB - Childhood obesity is a profoundly complex problem and serves as an example of a biospsychosocial issue. Scientific inquiry has provided incredible insight into the complex etiology of weight gain but must be viewed as an interaction between a human's propensity to conserve calories for survival in a world with an abundance of it. This article provides a brief overview divided between biological (nature) and psychosocial and behavioral (nurture) factors. PMID- 22093857 TI - Advances in pediatric nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of pediatric liver disease in the developed world. Children have a form of NAFLD that is pathologically distinct from adults. Although NAFLD remains a pathologic diagnosis, biomarkers and imaging studies hold promise as noninvasive means of both establishing the diagnosis and following the disease course. Significant advancements have recently been made in genetics, pathophysiology, and the treatment of NAFLD. The purpose of this article is to provide a clinically relevant review of pediatric NAFLD with an emphasis on recent developments in the field. PMID- 22093856 TI - Dyslipidemia and pediatric obesity. AB - Cardiovascular disease is the leading cause of death in the United States despite a reduction in mortality over the past 4 decades. Much of this success is attributed to public health efforts and more aggressive treatment of clinical disease. The rising rates of obesity and diabetes, especially among adolescents and young adults, raise concern for increases in mortality. National vital statistics have shown a leveling of cardiovascular disease death rates in the fifth decade of life. Public health efforts have begun to address childhood obesity. This article reviews the dyslipidemia associated with obesity in childhood and outlines a proposed approach to management. PMID- 22093858 TI - Psychological complications of pediatric obesity. AB - Psychological complications associated with pediatric obesity include low self esteem, depression, body dissatisfaction, loss-of-control eating, unhealthy and extreme weight control behaviors, impaired social relationships, obesity stigma, and decreased health-related quality of life. Bioecological models offer a framework for understanding the interaction between pediatric obesity and psychological complications and illustrate system-level approaches for prevention and intervention. As the medical setting is often the first point of contact for families, pediatricians are instrumental in the identification and referral of children with psychological complications. Motivational interviewing, patient talking points, brief screening measures, and referral resources are important tools in this process. PMID- 22093860 TI - Practical approaches to the treatment of severe pediatric obesity. AB - Pediatric obesity is a major public health threat. Obese children and adolescents are at increased risk for many medical and surgical conditions. These conditions may affect their quality of life and life expectancy. The rapidly progressive nature of type 2 diabetes mellitus within the first 5 years of obesity diagnosis is particularly concerning. Because health risk increases with degree of obesity, adolescents who may be eligible for more aggressive obesity treatment should be identified and counseled. PMID- 22093859 TI - Counseling and behavior change in pediatric obesity. AB - To effectively intervene with the overweight and obese youth, it is imperative that primary care providers and behavioral interventionists work in concert to help families implement healthy behaviors across socioenvironmental domains. In this article, the authors review current office-based counseling practices and provide evidence-based recommendations for addressing weight status and strategies for encouraging behavior change with children and families, primarily by increasing social support. By providing such collaborative targeted efforts, consistent health messages and support are delivered across children's everyday contexts, thereby helping the youth to achieve successful implementation of eating and activity behaviors and sustainable weight loss outcomes. PMID- 22093861 TI - Strategies for pediatric practitioners to increase fruit and vegetable consumption in children. AB - High intake of fruits and vegetables (FV) is associated with a decreased risk for many chronic diseases and may assist in weight management, but few children and adolescents consume the recommended amounts of FV. The pediatric practitioner can positively influence FV consumption of children through patient-level interventions (eg, counseling, connecting families to community resources), community-level interventions (eg, advocacy, community involvement), and health care facility-level interventions (eg, creating a healthy food environment in the clinical setting). This article reviews the importance of FV consumption, recommended intakes for children, and strategies by which pediatric practitioners can influence FV consumption of children. PMID- 22093862 TI - The role of added sugars in pediatric obesity. AB - This article provides an overview for pediatricians and other health care providers of the role of added sugars (caloric sweeteners) in the diets of US children and the recent evidence linking added sugar consumption to increased obesity and other chronic disease risk in children. The hypothesized biologic mechanisms for these associations are summarized, and evidence-based strategies are provided that may help children and their families to reduce their sugar consumption. Primary health care providers play an important role in assessing the added sugar intake of their patients and in providing nutrition and behavior change counselling to high-risk children and their families. PMID- 22093863 TI - Artificial sweetener use among children: epidemiology, recommendations, metabolic outcomes, and future directions. AB - This review summarizes the literature pertaining to the epidemiology and current recommendations for pediatric artificial sweetener use and presents the results of studies investigating metabolic responses to artificial sweeteners among children. An understanding of the research previously conducted and the gaps that remain will inform future clinical and translational research, to develop evidence-based recommendations for artificial sweetener use in the prevention and treatment of pediatric obesity. PMID- 22093864 TI - The role of physical activity in pediatric obesity. AB - This article provides an overview of the benefits of physical activity in children, including the effects on obesity, cognitive development, academic achievement and cognition, and health. The recommendations of health organizations are also outlined, and practical recommendations are provided for parents and educators. PMID- 22093865 TI - The fault, dear viewer, lies not in the screens, but in ourselves: relationships between screen media and childhood overweight/obesity. AB - This article summarizes recent findings about associations between electronic screen media and childhood overweight/obesity, hypothesized mechanisms, and mediators. Recommendations are made for parents and clinicians. PMID- 22093866 TI - Media, social networking, and pediatric obesity. AB - The 5 years leading up to 2011 witnessed unprecedented transformations in the technology and media available to American consumers. These changes have led to major paradigmatic shifts in the way people think about media, how they use it, and the role they expect it to play in their lives. This article discusses the new media landscape and summarizes the evidence regarding media influences on pediatric obesity. Various effects on pediatric obesity are discussed and some conclusions and implications are provided, including possibilities and future directions for clinical practice and research. PMID- 22093867 TI - Policies to support obesity prevention for children: a focus on of early childhood policies. AB - Policies at many levels may help to shape environments that promote healthy weight and prevent obesity. We present policies to support obesity prevention for young children. We highlight policy Sand environmental systems change examples in the areas of promoting breastfeeding and providing healthy affordable food and information about food in community and child care settings and promoting physical activity in child care and the community. We address the role of the health care system and health care professionals to shape and advocate for policy and environmental systems change and provide resources for pediatric health care professionals to engage in community-based advocacy. PMID- 22093868 TI - Update in childhood and adolescent obesity. PMID- 22093869 TI - Multiple end joining mechanisms repair a chromosomal DNA break in fission yeast. AB - Non-homologous end joining (NHEJ) is an important mechanism for repairing DNA double-strand breaks (DSBs). The fission yeast Schizosaccharomyces pombe has a conserved set of NHEJ factors including Ku, DNA ligase IV, Xlf1, and Pol4. Their roles in chromosomal DSB repair have not been directly characterized before. Here we used HO endonuclease to create a specific chromosomal DSB in fission yeast and examined the imprecise end joining events allowing cells to survive the continuous expression of HO. Our analysis showed that cell survival was significantly reduced in mutants defective for Ku, ligase IV, or Xlf1. Using Sanger sequencing and Illumina sequencing, we have characterized in depth the repair junction sequences in HO survivors. In wild type cells the majority of repair events were one-nucleotide insertions dependent on Ku, ligase IV, and Pol4. Our data suggest that fission yeast Pol4 is important for gap filling during NHEJ repair and can extend primers in the absence of terminal base pairing with the templates. In Ku and ligase IV mutants, the survivors mainly resulted from two types of alternative end joining events: one used microhomology flanking the HO site to delete sequences of hundreds to thousands of base pairs, the other rejoined the break using the HO-generated overhangs but also introduced one- or two-nucleotide base substitutions. The chromosomal repair assay we describe here should provide a useful tool for further exploration of the end joining repair mechanisms in fission yeast. PMID- 22093871 TI - Superior performance of multilayered fluoropolymer films in low voltage electrowetting. AB - The requirement for low operational voltage in electrowetting devices, met using thin dielectrics, is usually connected with serious material failure issues. Dielectric breakdown (visible as electrolysis) is frequently evident slightly beyond the onset of the contact angle saturation. Here, plasma-enhanced chemical vapor deposition (PECVD) is used to deposit thin fluorocarbon films prior to the spin-coating of Teflon(r) amorphous fluoropolymer. The resulting multilayered hydrophobic top coating improves the electrowetting performance of the stack, by showing high resistance to dielectric breakdown at high applied voltages and for continuous long term application of DC and AC voltage. Leakage current measurements during electrowetting experiments with the proposed composite coating showed that current remains fairly constant at consecutive electrowetting tests in contrast to plain Teflon(r) coating in which material degradation is evident by a progressive increase in the leakage current after multiple electrowetting tests. Since the proposed composite coating demonstrates increased resistance to material failure and to dielectric breakdown even at thin configurations, its integration in electrowetting devices may impact their reliability, robustness, and lifetime. PMID- 22093870 TI - Androgen deprivation therapy before radical prostatectomy is associated with poorer postoperative erectile function outcomes. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Erectile dysfunction is a recognized complication of radical prostatectomy. Androgen deprivation therapy adversely impacts sexual function. Our study shows that the preoperative use of androgen deprivation therapy significantly reduces erectile function recovery after radical prostatectomy. The underneath pathophysiological mechanisms for this to occur are reviewed. OBJECTIVE: To define the impact of androgen deprivation therapy (ADT), undergone before radical prostatectomy (RP), on erectile function (EF) recovery. MATERIAL AND METHODS: A total of 38 consecutive patients presenting to a sexual medicine clinic after undergoing RP who had received ADT before RP (ADT+ group) were compared with a contemporary, age and comorbidity matched cohort of 94 patients who did not receive ADT (ADT- group) before undergoing RP. Medical records were reviewed for demographics, comorbidity profiles and duration of ADT exposure. All the patients underwent Doppler penile ultrasonography within 6 months of RP and were administered the International Index of Erectile Function (IIEF) questionnaire. All the patients underwent evaluation of EF recovery. We analysed the incidence of venous leak (VL), mean IIEF EF domain score and proportion of men with EF domain scores >= 24 at 18 months after RP. RESULTS: The mean age, comorbidity profiles, median Gleason score, median pre-treatment PSA level, and mean time to evaluation after RP were similar between the two groups. The median duration of ADT exposure in the ADT+ group was 3 months. The incidence of VL within 6 months of surgery was 60% for the ADT+ and 20% for the ADT- group (P < 0.001). Likewise, the IIEF EF domain scores and proportion of men with EF domain scores >= 24 at 18 months were significantly lower in the ADT+ group, even when controlled for nerve-sparing status. CONCLUSION: Our data suggest that preoperative use of ADT adversely impacts EF outcomes and should therefore be avoided in the absence of robust data suggesting any oncological benefit. PMID- 22093872 TI - In situ kinetic study of zinc sulfide activation using a quartz crystal microbalance with dissipation (QCM-D). AB - We have studied the activation kinetics of zinc sulfide (ZnS) using silver as an activator by a quartz crystal microbalance with dissipation (QCM-D). The zinc sulfide coating on QCM-D sensor was shown to have similar crystallographic structure, composition, and surface properties as nature sphalerite through the characterization of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and xanthate adsorption measurement using QCM-D. The activation of ZnS sensor by silver was confirmed by the mass increase in ZnS sensor coupled with subsequent xanthate adsorption during QCM-D measurement, the change of surface wettability, and the presence of Ag(2)S on the surface. Two distinct stages on the silver uptake vs. time curve were identified and fitted well by a logarithmic function for the initial stage and a parabolic law in the later stage, which agrees with the two-stage zinc-silver reaction kinetics reported previously. Argon sputtering followed by XPS measurement on the ZnS surface demonstrated the penetration of silver into the bulk ZnS after activation. The present study is the first of its kind to apply the QCM-D technique to investigate sphalerite activation, which introduces a new in situ approach to investigate surface adsorption and activation in many mineral processes and surface modifications. PMID- 22093873 TI - Synergistic effect of polycation and polyanion on silica polymerization. AB - Colloidal silica (SiO(2)) is perhaps the most undesirable inorganic deposit formed in industrial water treatment systems. SiO(2) can either be found in bulk or on surfaces, such as heat exchangers, pipelines, or membrane. Conventional mineral scale inhibitors cannot inhibit its formation. Chemical cleaning is difficult and not free from hazards. This paper reports the excellent inhibition efficiency of adipic acid/amine-terminated polyethers D230/diethylenetriamine copolymer (AA/AT/DE). However, a small amount of silica-AA/AT/DE white insoluble floc appears in the solution. To overcome this problem, polyepoxysuccinic acid (PESA) is introduced. PESA by itself cannot inhibit silica polymerization. However, the combination of PESA and AA/AT/DE cannot only prevent the white floc, but also improve the inhibition performance of AA/AT/DE. The underlying mechanism is investigated based on zeta potentials and atomic force microscopy topography. PMID- 22093874 TI - Evaluation of the NOD/SCID xenograft model for glucocorticoid-regulated gene expression in childhood B-cell precursor acute lymphoblastic leukemia. AB - BACKGROUND: Glucocorticoids such as prednisolone and dexamethasone are critical drugs used in multi-agent chemotherapy protocols used to treat acute lymphoblastic leukemia (ALL), and response to glucocorticoids is highly predictive of outcome. The NOD/SCID xenograft mouse model of ALL is a clinically relevant model in which the mice develop a systemic leukemia which retains the fundamental biological characteristics of the original disease. Here we report a study evaluating the NOD/SCID xenograft mouse model to investigate glucocorticoid induced gene expression. Cells from a glucocorticoid-sensitive xenograft derived from a child with B-cell precursor ALL were inoculated into NOD/SCID mice. When highly engrafted the mice were randomized into groups of 4 to receive dexamethasone 15 mg/kg by intraperitoneal injection or vehicle control. Leukemia cells were harvested from mice spleens at 0, 8, 24 or 48 hours thereafter, and gene expression analyzed on Illumina WG-6_V3 chips, comparing all groups to time 0 hours. RESULTS: The 8 hour dexamethasone-treated timepoint had the highest number of significantly differentially expressed genes, with fewer observed at the 24 and 48 hour timepoints, and with minimal changes seen across the time matched controls. When compared to publicly available datasets of glucocorticoid induced gene expression from an in vitro cell line study and from an in vivo study of patients with ALL, at the level of pathways, expression changes in the 8 hour xenograft samples showed a similar response to patients treated with glucocorticoids. Replicate analysis revealed that at the 8 hour timepoint, a dataset with high signal and differential expression, using data from 3 replicates instead of 4 resulted in excellent recovery scores of > 0.9. However at other timepoints with less signal very poor recovery scores were obtained with 3 replicates. CONCLUSIONS: The NOD/SCID xenograft mouse model provides a reproducible experimental system in which to investigate clinically-relevant mechanisms of drug-induced gene regulation in ALL; the 8 hour timepoint provides the highest number of significantly differentially expressed genes; time-matched controls are redundant and excellent recovery scores can be obtained with 3 replicates. PMID- 22093875 TI - Efficient transcription by RNA polymerase I using recombinant core factor. AB - Transcription of ribosomal DNA by RNA polymerase I is a central feature of eukaryotic ribosome biogenesis. Since ribosome synthesis is closely linked to cell proliferation, there is a need to define the molecular mechanisms that control transcription by RNA polymerase I. To fully define the factors that control RNA polymerase I activity, biochemical analyses using purified transcription factors are essential. Although such assays exist, one limitation is the low abundance and difficult purification strategies required for some of the essential transcription factors for RNA polymerase I. Here, we describe a new method for expression and purification of the three subunit core factor complex from Escherichia coli. We demonstrate that the recombinant material is more active than yeast-derived core factor in assays for RNA polymerase I transcription in vitro. Finally, we use recombinant core factor to differentiate between two opposing models for the role of the TATA-binding protein in transcription by RNA polymerase I. PMID- 22093876 TI - Distribution of a marker of germline methylation differs between major families of transposon-derived repeats in the human genome. AB - A potential relationship between transposon-derived repeats (TDR) and human germline methylation is of biological importance since many genes are flanked by TDR and methylation could affect the expression of nearby genes. Furthermore, DNA methylation has been suggested as a global defense mechanism against genome instability threatened by TDR. We studied the correlation between the density of HapMap methyl-associated SNPs (mSNPs), a marker of germline methylation, and proportion of TDR. After correcting for confounding variables, we found a negative correlation between proportion of Alu repeats and mSNP density for 125 1000 kb windows. Similar results were found for the most active subgroup of repeats. In contrast, a negative correlation between proportion of L1 repeats and mSNP density was found only in the larger 1000 kb windows. Using methylation data on germ cells (sperm) from the Human Epigenome Project, we found a lower proportion of Alu repeats adjacent (3-15 kb) to hypermethylated amplicons. On the contrary, there was a higher proportion of L1 repeats in the 3-5 kb of sequence flanking hypermethylated amplicons but not in the 10-15 kb flanks. Our data indicate a differential response to the major repeat families and that DNA methylation is unlikely to be a uniform global defense system against all TDR. It appears to play a role for the L1 subgroup, with sequences adjacent to L1 repeats methylated in response to their proximity. In contrast, sequences adjacent to Alu repeats appear to be hypomethylated, arguing against a role of methylation in germline defense against those elements. PMID- 22093877 TI - Polymorphism of estrogen response element in TFF1 gene promoter is associated with an increased susceptibility to gastric cancer. AB - TFF1 is a cysteine-rich protein that forms a characteristic trefoil domain through disulfide bonds, which render it resistant to vigorous conditions and it involves in maintaining the integrity of the gastric mucosa. Decreased expression of TFF1 gene plays a role in the development of gastric cancer. We examined the association between the promoter polymorphisms of the TFF1 gene and the risk of development of gastric cancer, in a case-control study including 199 controls and 141 patients with gastric cancer. Assessment of single nucleotide polymorphisms in the promoter region of the TFF1 gene was performed by sequencing and polymerase chain reaction-based restriction fragment length polymorphism. We found a statistically significant increased risk of gastric cancer associated with -394 TT genotypes (OR=8.78, CI=2.85-27.05, p<0.001) and CT (OR=1.64, CI=1.04 2.60, p=0.033). This single nucleotide polymorphism occurs naturally in an estrogen response element. According to induction of the TFF1 gene by estrogen, it is possible that the substitution of C to T results in a decreased estrogen receptor binding affinity to the estrogen response element and in turn it decreases the expression of the TFF1 gene that may be involved in development of gastric cancer over a lifetime. PMID- 22093878 TI - Expression of Escherichia coli cspA during early exponential growth at 37 degrees C. AB - CspA is a small (7.4 kDa) nucleic acid binding protein of Escherichia coli whose expression is stimulated after cold-stress but whose level is also extraordinarily high during the early phase of growth of non-stressed cells. In this study the relationship existing between cspA transcription/translation on the one hand and the acquisition of critical mass for cell division and chromosome replication, on the other, in stationary phase cells subjected to a nutritional up-shift at 37 degrees C has been analyzed. Measurements of optical density and viable counts, pulse-chase, real-time PCR and immunodetection experiments, as well as cytofluorimetric and DNA duplication analyses show that synthesis of new CspA molecules at 37 degrees C is not only restricted to the lag phase ensuing the nutritional up-shift, but continues also during the first stages of logarithmic growth, when cells have already started dividing; although the early synthesized molecules are diluted by the following cell divisions and new synthesis occurs at an extremely low level, cspA mRNA and CspA continue to be present. A possible explanation for the apparent paradox that cspA is activated not only following cold stress, but also under non-stress and other stress conditions which entail a down-regulation of bulk gene expression and protein synthesis is presented. PMID- 22093879 TI - Dynamics of Escherichia coli O157:H7 outbreak detection and investigation, Minnesota 2000-2008. AB - We determined characteristics of Escherichia coli O157:H7 pulsed-field gel electrophoresis clusters that predict their being solved (i.e. that result in identification of a confirmed outbreak). Clusters were investigated by the Minnesota Department of Health (MDH) using a dynamic iterative model. During 2000 2008, 19 (23%) of 84 clusters were solved. Clusters of >=3 isolates were more likely to be solved than clusters of two isolates. Clusters in which the first two case isolates were received at MDH on the same day were more likely to be solved than were clusters in which the first two case isolates were received over >=8 days. Investigation of clusters of >=3 E. coli O157:H7 cases increased the success of cluster investigations. PMID- 22093880 TI - Evaluation of the personal development portfolio in higher education: an explorative study. AB - Personal Development Profiles (PDPs) have been an important and necessary feature of United Kingdom (UK) Higher Education for more than a decade. There is significant agreement as to their core purpose and their key features are of relevance to higher education institutions internationally, irrespective of whether an equivalent formal system or process is in place. The aim of this exploratory study was to evaluate the use of PDPs within a Child Health Nursing Programme in a UK University, looking at the experiences of both teaching staff and of students coming to the end of their three year programme of study. A convenience sample of final year pre-registration Child Health Nursing students and their lecturers was used for the purposes of this study with mixed methods of collection used to generate the required data. A survey was conducted with questionnaires. Following the analysis of the questionnaires, a discussion group was undertaken with the students. A series of questions was developed to guide this discussion. The structure offered by the system of PDPs evaluated here was seen to offer much in the way of potential value. Staff saw it as offering direction, a tool for discussion and a clear time and reason for meeting their students. Students similarly appreciated the structure it provided, but did describe it as somewhat repetitive. These findings were clearly of use in terms of evaluating this ongoing work, but also offer the potential to inform the work of other educational institutions. PMID- 22093881 TI - Lecturers' experiences of facilitating guided group reflection with pre registration BSc Nursing students. AB - The development of reflective practitioners is integral to undergraduate nursing degree programmes. This study reports on lecturers' experiences of facilitating guided group reflection with pre-registration BSc Nursing students.The research purposively sampled lecturers (n=7) working in a department of nursing and midwifery at a third level institute in Ireland, all of whom were registered nurses. Using a qualitative research approach, data was collected through audio taped semi-structured individual interviews. The data were thematically analysed using guidelines developed by Braun and Clarke (2006). Tripartite researcher discussion and further analysis of these initial individual analyses led to consensus regarding the three themes arising from the study. These were: Being a facilitator; Facilitating reflective learning and Creating structure. The discussion centred on: having knowledge and experience to effectively facilitate guided group reflection; the influence of the facilitator's personal philosophy on reflection and adult learning on group facilitation; and finally concerns regarding professional responsibility in response to students' reflective practice accounts. PMID- 22093882 TI - Peer bullying in a pre-registration student nursing population. AB - Peer bullying is a major problem in schools and workplaces including the National Health Service. Although there are a few published studies exploring the incidence of peer bullying among university students, none is specific to pre registration nursing students. Nursing programmes are delivered across two campuses of the university however students registered at individual campuses do not mix which makes the experiences of each campus individual. The aim of this study was to explore the incidence and manifestation of peer bullying amongst pre registration nursing students in the university setting. The study describes the reported incidence of the three types of peer bullying behaviour: physical, verbal and non-verbal bullying. Participants in their final year of adult nurse education were asked to explore their perceptions of peer bullying, the frequency of witnessed or experienced behaviour and the location of where this behaviour occurred on the university campuses via a quantitative questionnaire. In total 190 students were surveyed with 156 (82%) responding. Participants reported peer bullying is experienced by student nurses on university premises and that academic members of staff are sometimes present when this behaviour is demonstrated. Reported levels of bullying decreased during their 2nd and 3rd years of the course compared to the foundation year. This decrease may have been in response to the university's strong anti-bullying stance. PMID- 22093883 TI - Critical conversations: developing a methodology for service user involvement in mental health nursing. AB - AIM: Recent policy initiatives have identified that service user involvement in the education, design and delivery of mental health services should be more evident. This paper will discuss a methodology that was developed to do this. METHOD: A small study was designed and undertaken to explore the needs of service users and carers when becoming involved in mental health care. This paper will discuss the methodology that was developed for the study in order to make involvement practices more visible. FINDINGS: A critical conversation or narrative was developed that identified three main themes. Developing relationships with service users and carers that share universal goals whilst respecting diverse needs and encouraging recovery were found to be valued by the participants. CONCLUSION: The paper will conclude by showing how this methodology can be equally applied in a learning context, relevant for mental health nurse education. PMID- 22093884 TI - Liver transplantation for refractory severe pruritus related to widespread multifocal hepatic focal nodular hyperplasia (FNH) in a child: case report and review of literature. AB - FNH is a rare and benign tumor of the liver. It is not a conventional indication for liver transplantation, and no transplant for FNH in a child has been reported to date. Multifocal FNH growing in adolescent age to a widespread tumor invading the whole liver and associated with severe refractory pruritus was an unusual indication for transplantation in a 13-yr-old girl. The operation and the follow up were uneventful, allowing full recovery and disappearance of pruritus. PMID- 22093885 TI - Energetic and biomechanical constraints on animal migration distance. AB - Animal migration is one of the great wonders of nature, but the factors that determine how far migrants travel remain poorly understood. We present a new quantitative model of animal migration and use it to describe the maximum migration distance of walking, swimming and flying migrants. The model combines biomechanics and metabolic scaling to show how maximum migration distance is constrained by body size for each mode of travel. The model also indicates that the number of body lengths travelled by walking and swimming migrants should be approximately invariant of body size. Data from over 200 species of migratory birds, mammals, fish, and invertebrates support the central conclusion of the model - that body size drives variation in maximum migration distance among species through its effects on metabolism and the cost of locomotion. The model provides a new tool to enhance general understanding of the ecology and evolution of migration. PMID- 22093886 TI - [Accuracy of transthoracic Doppler echocardiography in the estimation of pulmonary artery systolic pressures]. AB - OBJECTIVE: To investigate the qualitative accuracy of pulmonary artery systolic pressure (PASP) as estimated by transthoracic Doppler echocardiography (TDE). METHODS: A retrospective study was conducted on 102 adult patients with idiopathic pulmonary arterial hypertension undergoing Doppler echocardiography within 72 hours prior to right heart catheterization. During this period, all patients were stable without any specific drug therapy. Compared with right heart catheterization, the accuracy of PASP as measured by TDE was evaluated. RESULTS: Among them, there were 38 males and 64 females with an average age of (31 +/- 11) years old (range: 18 - 59 years old). There was a moderate correlation between the measurements of PASP by TDE and right heart catheterization (r = 0.64, P < 0.01). Through the analysis of Bland-Altman, the bias for the TDE estimates of PASP was 6.7 mm Hg with a 95% limit of agreement ranging from -47.6 to 34.3 mm Hg. There were 60 (58.8%) cases with absolute differences over 10 mm Hg between two methods. Overestimation and underestimation of PASP by TDE occurred in 15.7% (16/102) and 43.1% (44/102) respectively. The magnitude of pressure underestimation and overestimation was insignificant [(25 +/- 12) vs (26 +/- 16) mm Hg, P = 0.765]. The probability of underestimate was higher than that of overestimate. As to the corresponding diagnostic categories of severity that each subject would fall into for each technique, the diagnostic categories of 16 overestimated patients were in accordance. Among 44 underestimated patients, 9 (20.5%) had their pressure underestimated within one diagnostic category (minor error) while 2 (4.5%) were within two diagnostic categories (major error). CONCLUSION: Due to a frequent rate of inaccurate estimation of PASP, TDE can not replace right heart catheterization. TDE tends to underestimate PASP and results in a diagnostic misclassification of degree. PMID- 22093887 TI - [Relationship between plasma total homocysteine and mild cognitive impairment in senile patients with type 2 diabetes]. AB - OBJECTIVE: To explore the relationship between fasting plasma level of total homocysteine (tHcy) and mild cognitive impairment in senile patients with type 2 diabetes mellitus. METHODS: A total of 88 senile type 2 diabetics with mild cognitive impairment treated at our hospital from July 2008 to November 2010 were recruited into the MCI group while 52 senile type 2 diabetics into the DNC group. And the control group was composed of 36 healthy elders. The parameters of tHcy, total glyceride (TG), total cholesterol (TC), low density lipoprotein-C (LDL-C), high density lipoprotein-C (HDL-C), creatinine (Cr), hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2 h plasma glucose (2 hPG), fasting insulin (FINS), homeostasis model of insulin resistance (HOMA-IR), folic acid (FA) and vitamin B(12) (VitB(12)) were detected. RESULTS: The patients had a higher level of tHcy in the MCI group than those in the NCM and control groups [(11.3 +/- 1.8) vs (9.8 +/- 1.5) and (8.1 +/- 1.1) umol/L; P < 0.01]. ROC curve showed that tHcy level had some value of predicting the occurrence of mild cognitive impairment in senile patients with type 2 diabetes mellitus (AUC 0.825, 95%CI 0.758-0.893, P < 0.01). Logistic regression analysis showed that tHcy, SBP, HbA1c, 2 h PG, FINS, LDL-C, HOMA-IR, FA and VitB(12) [OR value: 3.64, 1.68, 1.10, 1.05, 0.81, 1.42, 0.83, 0.74, 0.86 (P < 0.05 or 0.01)] were independent risk factors of mild cognitive impairment in senile diabetic patients. CONCLUSION: Such factors as tHcy, SBP, HbA1c, FPG, 2 hPG, FINS, LDL-C, HOMA-IR, FA and VitB(12) induce senile patients with type 2 diabetes mellitus to suffer mild cognitive impairment. But tHcy level may play an important role in senile diabetic patients with mild cognitive impairment. PMID- 22093888 TI - [Application of sedation with a low dose of dexmedetomidine during intrathecal anesthesia in elderly patients]. AB - OBJECTIVE: To explore the feasibility and safety of sedation with a low dose of dexmedetomidine (DEX) during intrathecal anesthesia in the elderly patients. METHODS: Thirty elderly patients were randomly divided into the DEX group (n = 15) and the control group (n = 15). There were 13 males and 17 females with a mean age of 77 years old (range: 65 - 89 years old). After an induction of intrathecal anesthesia, the patients in the DEX group received an infusion of 0.4 ug*kg(-1)*h(-1) for 10 min. Then the infusion speed was adjusted between 0.2 and 0.4 ug*kg(-1)*h(-1) to maintain the values of bispectral index (BIS) at around 80. An equivalent volume of normal saline was administered in the control group. Blood pressure, heart rate, respiratory rate, pulse oxygen saturation (SpO2), end tidal carbon dioxide partial pressure (P(ET)CO(2)) and BIS were recorded at the beginning of DEX infusion, 10, 20, 30 and 60 min after DEX infusion beginning and at the end of surgery. The observer's assessment of alertness/sedation (OAA/S) scores and the clinical responses were also recorded. A statistical analysis was performed. RESULTS: All intraoperative hemodynamic and respiratory parameters were within the normal range in both groups. Compared with the beginning after infusion, blood pressure at the point of 10 min after infusion decreased about 10% - 15% (P < 0.05) in the DEX group. But there was no such change in the control group. The values of BIS also decreased significantly at each time point after 10 min infusion versus the beginning of administration (P < 0.05); as compared with the control group, the values of BIS also decreased significantly at 30, 60 min and the end of infusion (P < 0.05). The 95%confidence interval (CI) of BIS values were 70 - 95 in the DEX group and 80 - 100 in the control group (P < 0.05). In the DEX group, the OAA/S scores were significantly lower at the points of 20, 30, 60 min and the end of infusion versus the beginning after infusion. And it was also lower in the DEX group than that in the control group (95%CI: 3 - 4 vs 4 - 5, P < 0.05). No bradycardia occurred in the DEX group. Two of three patients with concurrent atrial fibrillation were converted to sinus rhythm after the administration of DEX. Patients with severe lung diseases (pulmonary fibrosis, asthma or chronic obstructive pulmonary disease) maintained normal cardiopulmonary functions in the DEX group. DEX showed a good sedation effect in 1 patient with mental diseases. CONCLUSION: Sedation with a small dose of DEX during intrathecal anesthesia in elderly patients is both feasible and efficacious. But studies of larger sample sizes are warranted to confirm its safety. PMID- 22093889 TI - [Surgical strategies on intravenous leiomyomatosis invading heart]. AB - OBJECTIVE: To explore the diagnostic features and therapeutic methods of intravenous leiomyomatosis with a potential of heart invasion. METHODS: Eight cases of cardiac involvement with intravenous leiomyomatosis treated at our hospital from November 2002 to August 2011 were analyzed and compared. RESULTS: Either imaging or surgery confirmed that in all 8 patients the pelvic lesions originated from the inferior vena cava and heart involvement without pulmonary embolism. In 3 cases, palpitations and chest tightness were noticed. Four cases showed lower extremity edema and abdominal distension while no obvious clinical symptom was found for 1 case. All 8 cases had a history of uterine fibroids and 6 underwent previous hysterectomy. Among 8 patients, there were 5 cases of cardiopulmonary bypassing right heart, inferior vena cava tumor resection and pelvic involvement vein ligation and 2 cases of routine off-pumping of inferior vena cava with pelvic tumor resection. Palliative therapy was administered in 1 case. Two patients were resection the right heart and inferior vena cava tumor in the cardiopulmonary bypass, 3 months later were resection gynecologic uterine, double-accessories and broad ligament and were not treated with hormone. After operation, another 5 surgery patients received high-dose hormone treatments. 2 cases of recurrence in each group were found by ultrasound follow-ups from 15 - 90 months. CONCLUSION: Invasion of the heart intravenous leiomyomatosis is a rare case, which can be tackled with a good effect by completely surgical resection and a limited effect on hormone therapy to prevent recurrence. PMID- 22093890 TI - [A meta-analysis of early percutaneous coronary intervention within 24 hours of thrombolysis in acute ST-elevation myocardial infarction]. AB - OBJECTIVE: To evaluate the efficacy and safety of early percutaneous coronary intervention (PCI) within 24 hours of thrombolysis in acute ST-elevation myocardial infarction. METHODS: The databases of Medline, EMBASE, Elsevier, Cochrane library, Wanfang and CNKI were searched for randomized controlled trials. Quality assessment and data extraction were performed by two independent reviewers. Statistical analyses were conducted with Stata 10.0 and RevMan 5.0 software. RESULTS: Eight studies (NORDI-STEMI, TRANSFER-AMI, WEST, CARESS-AMI, CAPITAL-AMI, GRACIA-I, SIAMI III & PRAGUE-I) involving a total of 3157 patients fulfilled the inclusion criteria. Meta-analysis results showed that, as compared with the control group, (1) the combined endpoint of 30 day mortality, re infarction and ischemia was significantly lower in early PCI within 24 h of thrombolysis group [relative risk (RR) = 0.52, 95% confidence interval (CI) 0.42 0.65, P < 0.001]; (2) 30-day re-infarction decreased in early PCI within 24 h of thrombolysis group (RR = 0.57, 95%CI 0.40 - 0.81, P = 0.002); (3) 30-day ischemia had a significant reduction in early PCI within 24 h of thrombolysis group (RR = 0.27, 95%CI 0.14 - 0.52, P < 0.001); (4) 30-day major hemorrhage or mortality rates were not significantly different between two groups (RR = 1.07, 95%CI 0.78 1.46, P = 0.69; RR = 0.86, 95%CI 0.62 - 1.20, P = 0.38 respectively). CONCLUSION: When primary PCI is not feasible, our meta-analysis favors early PCI within 24 h of thrombolysis for acute ST-elevation myocardial infarction. Early PCI is associated with a lowered recurrence of major adverse cardiac events, ischemia and re-infarction. But there is no elevated risk of major hemorrhage and mortality. PMID- 22093892 TI - [Extramammary Paget's disease of the scrotum: an analysis of 26 cases]. AB - OBJECTIVE: To investigate the clinical features, diagnosis and therapeutics of extramammary Paget's disease. METHODS: A total of 26 cases of scrotal Paget's disease were included. According to Ray staging, 16, 7 and 3 cases had A1, A2 and B stages of Peget's diseases respectively. All cases underwent surgical resection of their diseased sites after a biopsy. The excision margin was 2 cm apart from the edge of lesion. And resection depth reached deep fascia. During operation, frozen sections of excised tissue specimens in 18 cases were pathologically examined. And the excision margins were involved by tumor cell in 3 cases (16.67%). Thus extended excision was performed immediately. Postoperatively, excision margin involvement was confirmed in 1 case and phase II operation performed. Three cases with inguinal lymph node metastasis underwent unilateral or bilateral inguinal lymph node dissection. RESULTS: Paget's disease was confirmed in all 26 cases. Tumor was localized in epidemics in 15 cases and skin invasion found in 11 cases. The lymph node was tumescent in 9 cases. Among them, 3 had pathologically confirmed metastasis and 6 was diagnosed with lymphadenitis. All cases received a mean follow-up period of 5 years (range: 1 - 7 years). Five locally recurrent cases healed after a second operation. CONCLUSION: Chronic skin lesions of the scrotum should be biopsied as early as possible if extramammary Paget's disease is suspected. Radical resection of diseased skin is its preferred therapy. A second operation may be performed for recurrence. The prognosis of extramammary Paget's disease is excellent after radical surgery. PMID- 22093891 TI - [Autologous peripheral blood hematopoietic stem cell transplantation in the treatment of type 1 diabetic mellitus: a report of 16 cases]. AB - OBJECTIVE: To explore the efficacy and safety of autologous peripheral blood hematopoietic stem cell transplantation (APBHST) in patients with type 1 diabetes mellitus. METHODS: Hematopoietic stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor for 16 patients with type 1 diabetes mellitus who admitted to our department during November 2009 to August 2010. And then stem cells were collected from peripheral blood by leukapheresis and cryopreservation. The cells were infused intravenously after conditioning with cyclophosphamide and antithymocyte globulin. To compare the daily dose of exogenous insulin requirements, the serum levels of hemoglobin A1c (HbA1c), C peptide, islet cell function during the mixed meal tolerance test were measured before and at different times after APBHST. Blood glucose was monitored 7 times a day before and after APBHST. And the adverse effects were recorded during and after APBHST. RESULTS: The median follow-up was 28 weeks (range: 8 - 44 weeks). Twelve of 16 patients stayed free from insulin at 3 - 20 days post APBHST. And islet cell function greatly improved after APBHST. Four of 16 patients required exogenous insulin but the dosage decreased. And all 4 patients had a poor level of C-peptide before APBHSCT. There were no such severe adverse effects as myelosuppression. CONCLUSION: Very encouraging results have been obtained in the patients treated with APBHST. There is definite therapeutic effects and safety in a short term. But further follow-up is necessary to confirm the duration of insulin independence and the mechanisms of action. PMID- 22093893 TI - [Private hospital medical process of virtual team members impact on the analysis of differences]. AB - OBJECTIVE: To analyze the private hospital the individual characteristics of virtual team members to run the hospital medical process for the impact of the differences, the private hospital managers to develop management strategies for scientific and rational basis. METHODS: Four different regions of the empirical investigation of private hospitals, and the use of SPSS software for statistical analysis of survey data. RESULTS: The ages of staff in dealing with the original terms of team cohesion were significant differences; gender, education, job titles and other features of the nature and impact of medical procedures for the difference was not statistically significant. CONCLUSION: Older employees the minimum of the original team cohesion; women in trust and work among the members of the initiative are better than men; specialist qualifications of staff-level positive initiative, strongest work, job confidence among members of difference in performance prominent. PMID- 22093894 TI - [Evaluation of immune responses and related patho-inflammatory reactions of a candidate inactivated EV71 vaccine in neonatal monkeys]. AB - OBJECTIVE: To evaluate the safety of enterovirus type 71 (EV71) inactivated vaccine (human diploid derived) for infection prevention in an animal model by investigating the immune responses and related patho-inflammatory reactions. METHODS: In the neonatal monkey model for EV71 vaccine protection, vaccinated group (n = 4) and unvaccinated group (n = 4) were attacked with live virus at the same time, the parameters of clinical observations, antibodies and inflammatory factors in peripheral blood and cerebrospinal fluid (CSF) were detected. And the pathological changes in major organs were used to determine the patho inflammatory reactions during the immune responses elicited by vaccination. RESULTS: The neutralizing antibodies of vaccine group reach to 1:32. There was no obvious changes of inflammatory factors in peripheral blood and CSF of monkeys challenged or unchallenged by live virus. In peripheral blood of unvaccinated group, the level of basophilic granulocyte higher 4 - 5 times than normal level and the interferon-gamma (IFN-gamma) showed obvious increase. Live virus infected after 7 days, the interleukin-6 (IL-6) and IFN-gamma in peripheral blood of unvaccinated group (18.5, 12.7 pg/ml) were higher than vaccinated group (10.2, 7.6 pg/ml). Furthermore, the IL-6 in CSF (102.0 pg/ml) had 4 - 5 times increased than vaccinated group (12.4 pg/ml) at 7 days after virus exposure. Meanwhile, the pathological analysis revealed that no obvious changes were detected in CNS and other organs of vaccinated monkeys challenged with live virus. However, the pathological damages induced by virus infection could be determined in the unvaccinated control monkeys, including neuronal damage, massive cellular infiltration associated with pulmonary edema/hemorrhage and pulmonary/bronchial damage due to an infiltration of inflammatory cells. CONCLUSION: Capable of inducing an immune response, the EV71 inactivated vaccine offers protection to neonatal rhesus monkeys against the attacks of live virus. Based on the results of no patho-inflammatory reaction and pathological damage after viral infection in vaccinated animals, the excellent safety of this vaccine may be confirmed in neonatal monkey. PMID- 22093895 TI - [Therapeutic effect of transplantation of bone marrow mesenchymal stem cells over expressing Cx43 on heart failure in post-infarction rats]. AB - OBJECTIVE: To explore the therapeutic effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) over-expressing Cx43 on heart failure in post infarction rats. METHODS: Sixty SD rats were randomly divided equally into 4 groups: sham group, DMEM/F12 group injected with DMEM/F12, EGFP group with transplanted EGFP transfected BMSCs and Cx43 group with transplanted Cx43 transfected BMSCs. Myocardial infarction model was established by ligating anterior descending branch and the cells were transplanted after 30 minutes. At Week 4 post-infarction, the heart functions of rats were evaluated by echocardiography. After the rats were sacrificed, their tissue samples were collected. The areas of myocardial infarction and the levels of collagen fiber content were measured. And the expressions of EGFR and Cx43 were observed under laser confocal microscopy. The level of Cx43 mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: As compared with the DMEM/F12 group, cardiac function was improved significantly, myocardial infarct area shrunk and collagen fiber content decreased significantly in the EGFP and group in Cx43 groups the. Survival of BMSCs and the formation of gap junction between BMSCs and the host myocardium could be observed under laser confocal microscopy both in EGFP group and Cx43 groups. And the post-infarction, expression of Cx43 mRNA in myocardial tissue decreased significantly in the group DMEM/F12, when compared with sham group (0.18 +/- 0.05 vs 0.78 +/- 0.14, P < 0.01). There was no significant difference on expression of Cx43 mRNA between DMEM/F12 group and EGFP group (0.18 +/- 0.05 vs 0.20 +/- 0.09, P > 0.05). The lever of Cx43 mRNA was higher in group Cx43 than in group DMEM/F12 and group EGFP(0.39 +/- 0.14 vs 0.18 +/- 0.05, P < 0.01; 0.39 +/- 0.14 vs 0.20 +/- 0.09, P < 0.05). CONCLUSION: Transplantation of BMSCs attenuates ventricular remodeling and improves cardiac functions. It may result from the over-expression of Cx43 gene through its effects of improving gap junction remodeling and increasing electro-mechanical coupling between myocardial cells in peri-infarct area. PMID- 22093896 TI - [Effects of soy isoflavones and major active component genistein on the expression of ovarian estrogen receptor-alpha in rats]. AB - OBJECTIVE: To investigate the effects of soy isoflavones (SI) on the expression of estrogen receptor-alpha (ER-alpha) in senile rat ovaries and ovarian granulosa cell cultured in vitro treated with genistein, a major active component of SI. METHODS: The animal model of perimenopause rats was established by unforced aging. The animals were treated by intragastric administration (ig) with low (50 mg/kg), middle (158 mg/kg) and high (500 mg/kg) dose of SI for 8 weeks. The expressions of ER-alpha mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The granulosa cells of rat ovaries were isolated and administered with genistein (0, 0.1, 1, 5, 10, 100 umol/L) for 48 h and the expression levels of ER-alpha mRNA detected by RT-PCR. RESULTS: The ER-alpha mRNA expression levels of the low, middle and high dose groups of SI (0.207 +/- 0.014, 0.316 +/- 0.073 and 0.402 +/- 0.170 respectively) were higher than those of the model group (0.671 +/- 0.170) (all P < 0.01). The expression levels of ER-alpha protein for the low, middle and high dose groups of SI (7.35 +/- 4.90, 13.90 +/- 5.12 and 23.79 +/- 10.31 respectively) were higher than those of the model group (2.74 +/- 0.09) (all P < 0.01). The expression levels of ER-alpha mRNA in granulosa cells treated with 1, 5, 10 umol/L genistein for 48 h were 0.927 +/- 0.232, 1.067 +/- 0.154, 1.118 +/- 0.126 respectively (all P < 0.01). They were higher than those of the control group (0.671 +/- 0.170). But the expression levels of 100 umol/L genistein group were lower than those of the control group (P < 0.05). CONCLUSION: Soy isoflavones can up-regulate the expressions of ER-alpha mRNA and protein in senile rat ovaries. As a major active component of soy isoflavones, genistein can regulate the expressions ER-alpha mRNA in granulosa cells of rat ovaries. Such an effect is concentration-dependent. And 1-10 umol/L genistein may up-regulate the expression of ER-alpha mRNA. PMID- 22093897 TI - [Regulating action of iron regulatory protein-2 in iron metabolism of lung cancer]. AB - OBJECTIVE: To discuss the regulating mechanism of iron regulatory protein-2 (IRP2) in the iron metabolism of lung cancer. METHODS: The cultured A549 cells were divided into 3 groups: liposome group (including liposomes 20 mg/L), random oligonucleotide group (SCODN group) and antisense oligonucleotide group (ASODN group). And the liposome-mediated transfection was employed with the liposome and SCODN groups as controls. Reverse transcription-polymerase chain reaction (RT PCR) and Western blot were used to examine the mRNA and protein expressions of iron metabolism-related transferring (Tf), transferrin receptor (TfR) and ferritin (Fn) genes, etc. RESULTS: After a 48-hour transfection, the mRNA expression of Tf had no statistically significant difference among three groups (F = 2.18, P = 0.078); the mRNA expression of TfR in the ASODN group was significantly lower than that in the liposome and SCODN groups (P < 0.05). The expression of Fn mRNA in the ASODN group (0.56 +/- 0.06) was higher than that in the liposome (0.36 +/- 0.05) and SCODN groups (0.39 +/- 0.03) (P < 0.05). After a 48-hour transfection, the IRP2 protein expression of the ASODN group was significantly lower than those of the liposome and SCODN groups (P < 0.05). The Tf protein expression was not statistically different in three groups (F = 2.67, P = 0.088). The TfR protein expression of the ASODN group was lower than those of the liposome and SCODN groups (P < 0.05). And the Fn protein expression of the ASODN group was higher than those of the liposome and SCODN groups (P < 0.05). CONCLUSION: IRP2 may affect the expressions of TfR and Fn in lung adenocarcinoma A549 cells by changing the amount of protein and regulating the iron metabolism. PMID- 22093898 TI - [Mechanisms and dynamics of Th17 cells in mice with cigarette smoke-induced emphysema]. AB - OBJECTIVE: To evaluate the expression of Th17 cell in a cigarette smoke-induced mice model of emphysema and explore the probable mechanisms of its elevation. METHODS: Forty male Balb/c mice were randomly divided into 4 groups: control group for 12 weeks (C12), control group for 24 weeks (C24), smoke-exposure group for 12 weeks (S12) and smoke-exposure group for 24 weeks (S24)(n = 10 each). Morphological changes were evaluated by mean linear intercepts (Lm) and destructive index (DI). The percentages of Th17, Th1, Th17/Th1, CD4(+)IL 17(+)CCR6(+)T and CCR6(+)Th17 cells were determined by tetra-color flow cytometry while the levels of interleukin (IL)-1beta, IL-6, IL-23, transforming growth factor (TGF)-beta, interferon (IFN)-gamma and CC chemokine ligand (CCL)-20 assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The values of Lm [(39 +/- 4) um, (47 +/- 7) um] and DI [(39.1 +/- 1.6), (45.2 +/- 3.1)] were significantly higher in S12 and S24 than those in C12 [(33 +/- 3) um, (28.2 +/- 1.6)] and C24 [(32 +/- 4) um, (28.9 +/- 2.1)], particularly in C24 (all P < 0.05). The percentages of Th17 cell [(3.27 +/- 1.12), (7.19 +/- 2.24)], Th17/Th1 cell [(0.61 +/- 0.30), (1.82 +/- 0.52)] and Th1 cell [(10.02 +/- 3.68), (26.21 +/ 6.04)] in the lungs of S12 and S24 significantly increased than those in C12 [(1.80 +/- 0.75), (0.27 +/- 0.12), (3.75 +/- 1.72)] and C24 [(1.99 +/- 0.59), (0.28 +/- 0.11), (4.16 +/- 1.32)], particularly in C24 (all P < 0.01). The percentages of Th17, Th17/Th1 and Th1 cells in the lungs of S12 and S24 had a positive correlation with Lm and DI (all P < 0.01). The percentages of CD4(+)IL 17(+)CCR-6(+)T cell [(0.69 +/- 0.34), (1.11 +/- 0.48)] and CCR6(+)Th17 cell [(12.23 +/- 2.13), (18.65 +/- 1.17)] were significantly elevated in S12 and S24 compared to those in C12 [(0.22 +/- 0.18), (6.55 +/- 2.13)] and C24 [(0.25 +/- 0.17), (7.29 +/- 1.57)], particularly in C24 (all P < 0.05). Furthermore, a positive correlation between CCR6(+)Th17 cell and emphysematous lesions was also found (all P < 0.05). The levels of IL-1beta, IL-6, IL-23, TGF-beta, IFN-gamma and CCL20 significantly increased in S12 and S24 as compared with those of C12 and C24 (all P < 0.05). Meanwhile, the percentage of Th17 cell had a positive correlation with IL-1beta, IL-6, IL-23, TGF-beta, IFN-gamma and CCL20. CONCLUSION: There is an up-regulated expression of Th17 in lungs of cigarette smoke-induced emphysema mice. The CCR6/CCL20 axis and the elevated levels of IL 1beta, IL-6, IL-23, TGF-beta and IFN-gamma may be related with the above effect. PMID- 22093899 TI - [Effects and mechanisms of phosphodiesterase type 5 inhibitors on rats with overactive bladder]. AB - OBJECTIVE: To investigate the effects and the possible mechanistic pathway of phosphodiesterase type 5 (PDE5) inhibitors on rats with overactive bladder. METHODS: A total of 24 adult male spontaneously hypertensive rats (SHRs) were randomly divided into 3 groups: daily lavage group, discontinuous lavage group and blank group (n = 8 each). Daily vardenafil (10 mg*kg(-1)*d(-1)), discontinuous vardenafil (10 mg*kg(-1)*d(-1)) and daily normal saline were administered respectively to 3 groups by lavage. And 8 adult male SD rats were included into the control group. Bladder urodynamic examinations were conducted in each group 2 weeks later. Then bladder detrusor muscle strips isolated from each group were further divided into two parts. One part was first pre-contracted and then the relaxant effects of sodium nitroprusside and Y-27632 were observed. For another part, enzyme-linked immunosorbent assay was used to measure cyclic guanosine monophosphate (cGMP). RESULTS: As compared with the control group, the values of bladder inter contraction interval (ICI) and bladder capacity (BC) were significantly lower [(409 +/- 36) s vs (568 +/- 60) s, (284 +/- 25) ul vs (395 +/ 42) ul, P < 0.01] while the bladder non voiding contraction (NVC) was significantly higher in the blank group [(2.03 +/- 0.49) number/min vs(1.07 +/- 0.30) number/min, P < 0.01]. Compared with the blank group, the values of ICI and BC were elevated. NVC decreased obviously in the discontinues and daily lavage groups [(486 +/- 53) s and (564 +/- 44) s; (337 +/- 37) ul and (392 +/- 30) ul; (1.82 +/- 0.32) number/min and (0.52 +/- 0.23) number/min, P < 0.05]. The effects were more significant in the daily lavage group (P < 0.01). The maximal relaxant effect of sodium nitroprusside was obviously enhanced in the discontinues and daily lavage groups [(50.6 +/- 2.1)% and (67.9 +/- 4.1)% vs(25.3 +/- 5.0)%, P < 0.01]. However the sensitivity of Y-27632 decreased significantly [(35.8 +/- 2.5)% and (20.2 +/- 2.3)% vs (71.6 +/- 2.8)%, P < 0.01], while the level of cGMP was significantly higher in the bladder detrusor muscle [(20.6 +/- 4.1) fmol/mg and (29.4 +/- 4.3) fmol/mg vs (12.9 +/- 2.1) fmol/mg, P < 0.01]. The effects of the daily lavage group were more pronounced (P < 0.01). CONCLUSION: The phenomenon of bladder overactivity is observed in the SHRs. The PDE5 inhibitors are effective in treating overactive bladder. And the effect of daily supplement is much better. In addition, the mechanism may operate through the cGMP-dependent protein kinase G-RhoA/Rho kinase signaling pathway. PMID- 22093900 TI - [Effects of combined enteral nutrition support on hemorrheologic parameters and the level of inflammatory factors in rabbits with severe acute pancreatitis]. AB - OBJECTIVE: To explore the effects of combined enteral nutrition (CEN) on the hemorheologic parameters and the changing levels of inflammatory factors in an animal model of severe acute pancreatitis (SAP). METHODS: The experimental animals were divided randomly into 3 groups, i.e. early enteral nutrition (EEN) group, CEN group and parenteral nutrition(PN)group (n = 20 each). Enteral nutrition was administered to the EEN and CEN group animals at 24 h and 72 h post modeling respectively. The PN group animals were supported by parenteral nutrition all time. Hemorrheologic indices of all experimental animals were examined on Days 1, 3 and 7 post-modeling. And the inflammatory factors were examined on Days 1 and 7. RESULTS: Compared with the EEN and PN groups, some hemorrheologic indices of the CEN group decreased significantly (P < 0.05) on Day 7 post-modeling. They included blood sedimentation, hematocrit (HCT), whole blood high-cut reduction viscosity and whole blood low-cut reduction viscosity. As compared within the CEN group, each hemorrheologic index was lower on Day 7 than that on Day 1 (P < 0.05). Except for whole blood high-cut reduction viscosity and erythrocyte aggregation index in the EEN group after a 7-day nutrition support, there was no significant change for all hemorrheologic indices in the PN group. As to the level of inflammatory factors, the values of interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in the CEN group were lower than those in the PN group on Day 7 post-modeling (P < 0.05). The values of IL-8 and IL-6 in the CEN group were lower than those in the EEN group on the same day (P < 0.05). As compared within the CEN group, the values of IL-6 and TNF-alpha were lower on Day 7 than those on Day 1 post-modeling (P < 0.05). CONCLUSION: The modulatory mechanism of EN over SAP should be achieved by correcting hemorrheologic index change and lowering the level of inflammatory factors. A proper timing of EN is probably the most optimal nutrition support mode of SAP therapy. PMID- 22093901 TI - [Effects of cPKCbetaII/gamma membrane translocation ischemic/hypoxic tolerance induced by morphine postconditioning in hippocampal slices]. AB - OBJECTIVE: To determine whether or not morphine postconditioning can induce ischemic/hypoxic tolerance in neurons subjected to reperfusion injury after oxygen-glucose deprivation (OGD). METHODS: Hippocampal slices of 400 um thickness were prepared from healthy adult male BALB/c mice. The slices were incubated in oxygen-saturated ACSF without or with calcium, then were subjected to OGD for 20 min. After recovery, the samples were immersed in oxygenated artificial fluid for 2 hours in the presence or absence of morphine postconditioning at 3 umol/L during the first 5 - 60 min. The assessment of slices injury was performed by a determination of the intensity of slice stain incubated with TTC (2% 2, 3, 5 triphenyltetrazolium chloride) and the leakage rate of LDH also evaluated. At the designated periods during incubation, some slices were immersed into liquid nitrogen for a later analysis of Western blot. The frozen slices were homogenized, sonicated and centrifuged to separate soluble and particulate proteins. 10% SDS-PAGE Western blot was used to identify the changes of membrane specific translocation of cPKCbetaII/gamma. RESULTS: After reperfusion, the cell survival significantly decreased with the elongation of OGD (51.4%). The release rate of LDH (184.05%) significantly increased simultaneously. In hippocampal slices postconditioned with morphine for 20 - 60 min, the release rate of LDH (136%, 142%, 144%) significantly decreased as compared with the group OGD. In the hippocampal slices postconditioned with morphine for 10 - 30 min, the cell survival rate (64.9%, 69.9%, 63.5%) significantly increased as compared with reperfusion alone. cPKCgamma of particulate fraction increased versus the control. And there was a corresponding decrease of cytosolic fraction. Morphine postconditioning significantly inhibited the cPKCgamma isoform-specific membrane translocation. It declined from 136% in the group OGD to 123%, 118%, 114% in the group morphine 20 - 60 min. cPKCbetaII membrane translocation had no change. CONCLUSION: Morphine postconditioning can induce ischemic tolerance in nerons. The protective mechanism may be through inhibiting the cPKCgamma isoform-specific membrane translocation. PMID- 22093902 TI - Exposure to repeated maternal aggression induces depressive-like behavior and increases startle in adult female rats. AB - The stress response is a multifaceted physiological reaction that engages a wide range of systems. Animal studies examining stress and the stress response employ diverse methods as stressors. While many of these stressors are capable of inducing a stress response in animals, a need exists for an ethologically relevant stressor for female rats. The purpose of the current study was to use an ethologically relevant social stressor to induce behavioral alterations in adult female rats. Adult (postnatal day 90) female Wistar rats were repeatedly exposed to lactating Long Evans female rats to simulate chronic stress. After six days of sessions, intruder females exposed to defeat were tested in the sucrose consumption test, the forced swim test, acoustic startle test, elevated plus maze, and open field test. At the conclusion of behavioral testing, animals were restrained for 30 min and trunk blood was collected for assessment of serum hormones. Female rats exposed to maternal aggression exhibited decreased sucrose consumption, and impaired coping behavior in the forced swim test. Additionally, female rats exposed to repeated maternal aggression exhibited an increased acoustic startle response. No changes were observed in female rats in the elevated plus maze or open field test. Serum hormones were unaltered due to repeated exposure to maternal aggression. These data indicate the importance of the social experience in the development of stress-related behaviors: an acerbic social experience in female rats precipitates the manifestation of depressive like behaviors and an enhanced startle response. PMID- 22093903 TI - Wastewater irrigation and environmental health: implications for water governance and public policy. AB - Climate change is a large-scale and emerging environmental risk. It challenges environmental health and the sustainability of global development. Wastewater irrigation can make a sterling contribution to reducing water demand, recycling nutrients, improving soil health and cutting the amount of pollutants discharged into the waterways. However, the resource must be carefully managed to protect the environment and public health. Actions promoting wastewater reuse are every where, yet the frameworks for the protection of human health and the environment are lacking in most developing countries. Global change drivers including climate change, population growth, urbanization, income growth, improvements in living standard, industrialization, and energy intensive lifestyle will all heighten water management challenges. Slowing productivity growth, falling investment in irrigation, loss of biodiversity, risks to public health, environmental health issues such as soil salinity, land degradation, land cover change and water quality issues add an additional layer of complexity. Against this backdrop, the potential for wastewater irrigation and its benefits and risks are examined. These include crop productivity, aquaculture, soil health, groundwater quality, environmental health, public health, infrastructure constraints, social concerns and risks, property values, social equity, and poverty reduction. It is argued that, wastewater reuse and nutrient capture can contribute towards climate change adaptation and mitigation. Benefits such as avoided freshwater pumping and energy savings, fertilizer savings, phosphorous capture and prevention of mineral fertilizer extraction from mines can reduce carbon footprint and earn carbon credits. Wastewater reuse in agriculture reduces the water footprint of food production on the environment; it also entails activities such as higher crop yields and changes in cropping patterns, which also reduce carbon footprint. However, there is a need to better integrate water reuse into core water governance frameworks in order to effectively address the challenges and harness the potential of this vital resource for environmental health protection. The paper also presents a blueprint for future water governance and public policies for the protection of environmental health. PMID- 22093904 TI - Intimate partner violence among women with HIV infection in rural Uganda: critical implications for policy and practice. AB - BACKGROUND: Intimate partner violence (IPV) is a major public health problem in Africa and worldwide. HIV infected women face increased IPV risk. We assessed the prevalence and factors associated with IPV among HIV infected women attending HIV care in Kabale hospital, Uganda. METHODS: This cross-sectional study was conducted among 317 HIV infected women attending Kabale regional hospital HIV treatment centre, from March to December 2010. Participants were interviewed using an interviewer-administered questionnaire. Data was collected on socio demographic variables, social habits, and IPV (using the abuse assessment screen and the Severity of Violence against Women Scale to identify physical, sexual and psychological violence). Characteristics of the participants who reported IPV were compared with those who did not. Multivariate logistic-regression analysis was conducted to analyze factors that were independently associated with IPV. RESULTS: The mean age of 317 respondents was 29.7 years. Twenty two (6.9%) were adolescents and 233 (73.5%) were married or cohabiting. The mean age of the spouse was 33.0 years.One hundred and eleven (35.0%) were currently on antiretroviral therapy. Lifetime prevalence of IPV (physical or sexual) was 36.6%. In the preceding 12 months, IPV (any type) was reported by 93 respondents (29.3%). This was physical for 55 (17.6%), and sexual /psychological for 38 (12.1%). On multivariate multinomial logistic regression analysis, there was a significant but inverse association between education level and physical partner violence (adjusted relative risk (ARR) 0.50, confidence limits (95% CI) 0.31 0.82, p-value = 0.007). There was a significant but inverse association between education level of respondent and sexual/psychological violence (ARR 0.47 95%CI (0.25-0.87), p-value = 0.017) Likewise, there was a significant inverse association between the education level of the spouse and psychological/sexual violence (ARR 0.57, 95% CI 0.25-0.90, p-value = 0.018). Use of antiretroviral therapy was associated with increased prevalence of any type of violence (physical, sexual or psychological) with ARR 3.04 (95%CI 1.15-8.45, p-value = 0.032). CONCLUSION: Almost one in three women living with HIV had suffered intimate partner violence in the preceding 12 months. Nearly one in five HIV patients reported physical violence, and about one in every seven HIV patients reported sexual/psychological violence. Likewise, women who were taking antiretroviral drugs for HIV treatment were more likely to report any type of intimate partner violence (physical, sexual or psychological). The implication of these findings is that women living with HIV especially those on antiretroviral drugs should be routinely screened for intimate partner violence. PMID- 22093905 TI - Expression of the human tumor suppressor p53 induces cell death in Pichia pastoris. AB - The human tumor suppressor p53 is known as guardian of genome because of its involvement in many signals related to cell life or death. In this work, we report that human p53 induces cell death in the yeast Pichia pastoris. We showed a growth inhibition effect, which increased with the p53 protein expression level in recombinant Mut(s) (methanol utilization slow) strain of Pichia. However, no effect of p53 was observed in recombinant strain of Mut(+) (methanol utilization plus) phenotype. Interestingly, human p53 induces cell death in recombinant strains Mut(s) with characteristic markers of apoptosis such as DNA fragmentation, exposure of phosphatidylserine, and reactive oxygen species generation. Taken together, our results strongly suggest that human p53 is biologically active in this heterologous context. Thus, we propose that P. pastoris could be a useful tool to better understand the biological function of human p53. PMID- 22093906 TI - First evidence of previously undescribed trichomonad species in the intestine of pigs? AB - Three different parasites of the phylum Parabasala (Tritrichomonas foetus, Trichomitus rotunda and Tetratrichomonas buttreyi) have been described in pigs. In a previous study (Mostegl et al., 2011) approximately 47% of 91 paraffin wax embedded intestinal samples of pigs which were Trichomonas-positive by in situ hybridization using a probe with a broad reactivity spectrum contained other species than T. foetus. Out of these, intestinal trichomonads from three pigs (pigs 1-3) were further analyzed by gene sequencing of a part of the 18S ribosomal RNA (rRNA) gene using primer walking. Subsequently, the partial sequences achieved by the different primer pairs were combined to a sequence of about 1000 bp for each trichomonad. In all three pigs unique sequences were acquired which showed only moderate similarities to sequences available in the GenBank. Alignments and the BLAST analysis showed a high degree of homology between sequences of trichomonads from pig 1 and pig 3 with only 1% difference. These sequences were found to be 92% similar to Hypotrichomonas acosta, a trichomonad isolated from squamate reptiles. The trichomonad sequence detected in the intestine of pig 2 showed about 10% nucleotide differences compared to pigs 1 and 3. This sequence was 97% similar to two Trichomitus batrachorum (a frog symbiont) sequences. A phylogenetic analysis using the neighbor-joining and maximum likelihood methods supported the data of the BLAST analysis. These results suggest the presence of at least two as yet undescribed trichomonad species in the intestinal contents of pigs. PMID- 22093907 TI - Heterorhabditis bacteriophora (Rhabditida: Heterorhabditidae) HP88 for biological control of Rhipicephalus microplus (Acari: Ixodidae): the effect of different exposure times of engorged females to the nematodes. AB - The aim of this study was to assess the influence of different exposure times of engorged female the Rhipicephalus microplus to infective juveniles of Heterorhabditis bacteriophora isolate HP88. The engorged females were divided into seven groups (six treatments and one control) of 20 ticks each with statistically similar average weights (p>0.05) and exposed to concentrations of 300 nematodes/tick for periods of 3, 6, 12, 24, 48 and 72 h. The following biological parameters were monitored: pre-oviposition period; egg mass weight; hatching percentage; and efficacy of treatment. There was no influence of the exposure time on the pre-oviposition period (p>0.05), while there were significant differences (p<0.05) between the groups exposed for 24, 48 and 72 h and the control group with respect to the egg mass weight, and 24h for hatching percentage. Treatment efficacy reached 100% after exposure for 48 and 72 h. These results demonstrate that infective juveniles of H. bacteriophora HP88, under laboratory conditions, interfere in the majority of the biological parameters of the non-parasitic phase of engorged R. microplus females when the exposure time is greater than or equal to 24h. PMID- 22093908 TI - Effect of infection with Teladorsagia circumcincta on milk production and composition in Assaf dairy sheep. AB - Infection by gastrointestinal nematodes (GIN) in grazing sheep can negatively influence the growth of lambs and milk yield. In the current study we evaluated the effect of high and low levels of infection with Teladorsagia circumcincta on production parameters of lactating ewes. Two groups of ewes were infected with 50,000 T. circumcincta third stage larvae (L3) 30 days before lambing. To obtain a high level of infection, Group HI was challenged with 30,000 L3 30 days post partum (pp) and again 90 days pp with the same dose. The low infection group (LI) was treated with an intraruminal controlled-release albendazole bolus one-month pp. We determined the effect of the differing parasite loads on milk yield, milk composition, weight gain, and body condition (BC). Throughout the trial the milk yield was higher in the LI group and, consequently, at the end of the lactation, this group produced 11.1% more milk than the HI group. In the final third of lactation there was an overall increase in milk fat, protein, and lactose although the factor most affected by infection level was the protein percentage, with an increment of 11.9% in the HI group. The somatic cell counts remained low during the experiment indicating the absence of udder infection. Regarding weight and BC, significant differences were found only in BC although LI ewes weighed 2% more than the HI group. In conclusion, a low level of GIN infection in sheep leads to a better BC and a higher milk production with high protein percentage. PMID- 22093909 TI - The inverse agonist effect of rimonabant on G protein activation is not mediated by the cannabinoid CB1 receptor: evidence from postmortem human brain. AB - Rimonabant (SR141716) was the first potent and selective cannabinoid CB1 receptor antagonist synthesized. Several data support that rimonabant behaves as an inverse agonist. Moreover, there is evidence suggesting that this inverse agonism may be CB1 receptor-independent. The aim of the present study was to elucidate whether the effect of rimonabant over G protein activation in postmortem human brain is CB1 dependent or independent. [(35)S]GTPgammaS binding assays and antibody-capture [(35)S]GTPgammaS scintillation proximity assays (SPA) were performed in human and mice brain. [(3)H]SR141716 binding characteristics were also studied. Rimonabant concentration-dependently decreased basal [(35)S]GTPgammaS binding to human cortical membranes. This effect did not change in the presence of either the CB1 receptor agonist WIN 55,212-2, the CB1 receptor neutral antagonist O-2050, or the CB1 allosteric modulator Org 27569. [(35)S]GTPgammaS binding assays performed in CB1 knockout mice brains revealed that rimonabant inhibited the [(35)S]GTPgammaS binding in the same manner as it did in wild-type mice. The SPA combined with the use of specific antibody-capture of G(alpha) specific subunits showed that rimonabant produces its inverse agonist effect through G(i3), G(o) and G(z) subtypes. This effect was not inhibited by the CB1 receptor antagonist O-2050. Finally, [(3)H]SR141716 binding assays in human cortical membranes demonstrated that rimonabant recognizes an additional binding site other than the CB1 receptor orthosteric binding site recognized by O 2050. This study provides new data demonstrating that at least the inverse agonist effect observed with >1MUM concentrations of rimonabant in [(35)S]GTPgammaS binding assays is not mediated by the CB1 receptor in human brain. PMID- 22093910 TI - Towards a new treatment for equine acute laminitis: the importance of signalling pathways. PMID- 22093911 TI - The effect of radiological hip dysplasia and breed on survival in a prospective cohort study of four large dog breeds followed over a 10 year period. AB - The aim of the study was to measure the effect of radiological hip and elbow dysplasia status and breed on overall survival in a cohort of four large dog breeds in Norway. Privately owned dogs of the Newfoundland (NF), Labrador Retriever (LR), Leonberger (LEO), and Irish Wolfhound (IW) breeds were followed prospectively from birth to 10 years of age. The age of death/euthanasia was registered. A total of 501 dogs from 103 litters were enrolled. Kaplan-Meier survival curves were used to describe breed differences in survival times. The effects of radiological hip and elbow dysplasia status as well as breed were assessed using a Cox proportional hazards model. The variables 'sex' and 'living region' were explored as potential confounders. Among LRs, 60.2% of the dogs were still alive at 10 years of age, and the corresponding figures for NFs, LEOs, and IWs were 28.8%, 16.11%, and 6.4%, respectively. Radiological hip dysplasia status and breed were found to influence overall survival. Two different time-varying effects were observed in that with the IW the hazard of death increased linearly through time, while the effect of severe radiological hip dysplasia decreased logarithmically with time. Location influenced the death hazard and dogs living in suburban areas or cities had longer mean time to death and a lower hazard compared to dogs living in the countryside. Radiological elbow dysplasia status was not found to have an effect on overall survival. PMID- 22093912 TI - Cost-effectiveness analysis of newer anticholinergic drugs for urinary incontinence vs oxybutynin and no treatment using data on persistence from the Swedish prescribed drug registry. AB - Study Type - Therapy (cost effectiveness). Level of Evidence 2a. What's known on the subject? and What does the study add? Anticholinergic drugs are a common treatment alternative in urinary incontinence, which results in large costs for caregivers. So far, most cost-effectiveness analyses of anticholinergic drugs have focused on small putative differences between the newer anticholinergics. This study takes a novel approach by treating the clinical effects of the newer alternatives as similar and evaluating them as a group in relation to no treatment and oxybutynin (immediate release). It also uses registry data to account for persistence. OBJECTIVE: * To analyse the cost-effectiveness of newer anticholinergic drugs in relation to oxybutynin immediate release (IR) and no treatment for patients with urgency urinary incontinence. PATIENTS AND METHODS: * A decision analytic model was constructed. * Results were collected from randomized trials and combined with registry data on persistence of medicine use and estimated number of severe adverse events. * The setting corresponds to Swedish clinical practice. * The costs and effects of the treatment options were analysed over a period of 1 year. Costs included drug costs, treatment costs and costs for pad use. Patients' utilities were based on treatment effect and the lack or presence of adverse events. RESULTS: * No treatment was the least costly treatment but also resulted in the fewest number of quality adjusted life years (QALYs). * Treatment with newer anticholinergic drug medications is the most costly option but also the most efficient treatment. Sensitivity analyses showed that the results were robust. * Treatment with newer anticholinergics resulted in a cost per QALY gained of ?21 045 compared with no treatment and no effect and ?65 435 compared with no treatment and placebo effect. Compared with oxybutynin IR, the cost per QALY gained was ?37 119. These calculations are based on relatively low pad costs, resulting in higher costs per QALY for the original drugs. CONCLUSIONS: * The newer anticholinergic medications are likely to be cost effective in relation to oxybutynin IR. * The cost-effectiveness of the newer anticholinergics compared with no treatment depends on assumptions of the effect of no treatment, the severity of the treated condition and the treated individual's risk of adverse events. * Treatment is less likely to be cost effective for elderly persons or for persons otherwise at higher risk for adverse events. PMID- 22093913 TI - Six-month incidence of bloodstream infections in intestinal transplant patients. AB - BACKGROUND: Intestinal transplantation has emerged as an established treatment for life-threatening intestinal failure. The most common complication and cause of death is infection. Risk of infection is highest during the first 6 months, as a consequence of maximal immunosuppression, greater than that required for any other organ allograft. METHODS: We performed a retrospective chart review of all (56) adult and pediatric (<18 years) small bowel transplant patients at our institution between November 2003 and July 2007, and analyzed the 6-month post transplant incidence of bloodstream infections (BSIs). We evaluated multiple risk factors, including inclusion of a colon or liver, total bilirubin >5, surgical complications, and acute rejection. RESULTS: A BSI developed in 34 of the 56 patients, with a total of 85 BSI episodes. Of these BSI episodes, 65.9% were due to gram-positive organisms, 34.1% gram-negative organisms, and 2.4% due to fungi. The most common isolates were Enterococcus species, Enterobacter species, Klebsiella species, and coagulase-negative staphylococci. Inclusion of the liver and/or a preoperative bilirubin >5 mg/dL appeared to increase the incidence of BSI (P = 0.0483 and 0.0005, respectively). Acute rejection and colonic inclusion did not appear to affect the incidence of BSI (P = 0.9419 and 0.8248, respectively). The BSI incidence was higher in children (P = 0.0058). CONCLUSIONS: BSIs are a common complication of intestinal transplantation. Risk factors include age <18, inclusion of the liver, and pre-transplant bilirubin >5. Acute rejection and colon inclusion do not appear to be associated with increased BSI risk. PMID- 22093914 TI - The effect of anemia and white matter hyperintensities (WMH) on cognitive impairment in patients with amnestic mild cognitive impairment (MCI). AB - Anemia and subcortical ischemic change might be associated with increased risks for cognitive impairment among the elderly. This study examined the associations among anemia, WMH and cognitive function in patients with amnestic MCI. We recruited 278 subjects with amnestic MCI from the Clinical Research Center for Dementia of South Korea (CREDOS), a hospital-based cohort study. A standardized neuropsychological battery, containing tests of language, visuospatial function, verbal memory and executive function, was used for all patients. Anemia was defined as a hemoglobin concentration below 12 g/dl for women and below 13 g/dl for men. The severity of WMH was also examined using brain magnetic resonance imaging (MRI). After multivariable adjustments, anemia and WMH were associated with poorer performance on cognitive function tests (anemia: Stroop test, F=4.17, p=0.042; WMH: Stroop test, F=6.45, p=0.002; Rey-complex figure test-copy, F=4.08, p=0.018). Moreover, a significant interaction between anemia and the severity of WMH was observed in performance on the Go/no go test (F=4.50, p=0.012) and the Stroop test (F=3.36, p=0.037). In post hoc analysis, anemic patients with severe WMH had significantly worse scores on measure of executive function (Go/no go test, p=0.011; Stroop test, p=0.001). Anemia and WMH had interactive effects on executive function impairment among the elderly with amnestic MCI. PMID- 22093915 TI - The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain. AB - BACKGROUND: Clinical studies of osteoarthritis (OA) suggest central sensitization may contribute to the chronic pain experienced. This preclinical study used the monosodium iodoacetate (MIA) model of OA joint pain to investigate the potential contribution of spinal sensitization, in particular spinal glial cell activation, to pain behaviour in this model. Experimental OA was induced in the rat by the intra-articular injection of MIA and pain behaviour (change in weight bearing and distal allodynia) was assessed. Spinal cord microglia (Iba1 staining) and astrocyte (GFAP immunofluorescence) activation were measured at 7, 14 and 28 days post MIA-treatment. The effects of two known inhibitors of glial activation, nimesulide and minocycline, on pain behaviour and activation of microglia and astrocytes were assessed. RESULTS: Seven days following intra-articular injection of MIA, microglia in the ipsilateral spinal cord were activated (p < 0.05, compared to contralateral levels and compared to saline controls). Levels of activated microglia were significantly elevated at day 14 and 21 post MIA injection. At day 28, microglia activation was significantly correlated with distal allodynia (p < 0.05). Ipsilateral spinal GFAP immunofluorescence was significantly (p < 0.01) increased at day 28, but not at earlier timepoints, in the MIA model, compared to saline controls. Repeated oral dosing (days 14-20) with nimesulide attenuated pain behaviour and the activation of microglia in the ipsilateral spinal cord at day 21. This dosing regimen also significantly attenuated distal allodynia (p < 0.001) and numbers of activated microglia (p < 0.05) and GFAP immunofluorescence (p < 0.001) one week later in MIA-treated rats, compared to vehicle-treated rats. Repeated administration of minocycline also significantly attenuated pain behaviour and reduced the number of activated microglia and decreased GFAP immunofluorescence in ipsilateral spinal cord of MIA treated rats. CONCLUSIONS: Here we provide evidence for a contribution of spinal glial cells to pain behaviour, in particular distal allodynia, in this model of osteoarthritic pain. Our data suggest there is a potential role of glial cells in the central sensitization associated with OA, which may provide a novel analgesic target for the treatment of OA pain. PMID- 22093916 TI - Protein composition of interband regions in polytene and cell line chromosomes of Drosophila melanogaster. AB - BACKGROUND: Despite many efforts, little is known about distribution and interactions of chromatin proteins which contribute to the specificity of chromomeric organization of interphase chromosomes. To address this issue, we used publicly available datasets from several recent Drosophila genome-wide mapping and annotation projects, in particular, those from modENCODE project, and compared molecular organization of 13 interband regions which were accurately mapped previously. RESULTS: Here we demonstrate that in interphase chromosomes of Drosophila cell lines, the interband regions are enriched for a specific set of proteins generally characteristic of the "open" chromatin (RNA polymerase II, CHRIZ (CHRO), BEAF-32, BRE1, dMI-2, GAF, NURF301, WDS and TRX). These regions also display reduced nucleosome density, histone H1 depletion and pronounced enrichment for ORC2, a pre-replication complex component. Within the 13 interband regions analyzed, most were around 3-4 kb long, particularly those where many of said protein features were present. We estimate there are about 3500 regions with similar properties in chromosomes of D. melanogaster cell lines, which fits quite well the number of cytologically observed interbands in salivary gland polytene chromosomes. CONCLUSIONS: Our observations suggest strikingly similar organization of interband chromatin in polytene chromosomes and in chromosomes from cell lines thereby reflecting the existence of a universal principle of interphase chromosome organization. PMID- 22093917 TI - Comparison of endocrine-mediated effects of two bisphenol A related compounds, 2,2-bis(4-cyanatophyenyl)propane and 4,4'-cyclohexylidenebisphenol, based on subacute oral toxicity studies using rats. AB - The purpose of this study was to compare endocrine-mediated effects of bisphenol A related compounds, 2,2-bis(4-cyanatophyenyl)propane and 4,4' cyclohexylidenebisphenol with reference to OECD Test Guideline No. 407. Rats were orally gavaged with 0, 4, 20, and 100 mg/kg/day of 2,2-bis(4 cyanatophyenyl)propane, and 0, 30, 100, and 300 mg/kg/day of 4,4' cyclohexylidenebisphenol for at least 28 days beginning at 8 weeks of age. Endocrine-mediated effects were not observed in rats given 2,2-bis(4 cyanatophyenyl)propane. Male accessory sex organ weights decreased in the 4,4' cyclohexylidenebisphenol 300 mg/kg group and serum T4 values increased in all male groups treated with this compound. Our results suggest that endocrine mediated changes caused by the present bisphenol related compound can be divided into estrogenic or thyroid hormonal effects, and estrogenic effects observed in the repeated-dose study were related to their estrogenic potency confirmed by uterotrophic assay. PMID- 22093918 TI - Hesperidin alleviates acetaminophen induced toxicity in Wistar rats by abrogation of oxidative stress, apoptosis and inflammation. AB - Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The present study demonstrates the comparative hepatoprotective and nephroprotective activity of hesperidin (HD), a naturally occurring bioflavonoid against APAP induced toxicity. APAP induces hepatotoxicity and nephrotoxicity as was evident by abnormal deviation in the levels of antioxidant enzymes. Moreover, APAP induced renal damage by inducing apoptotic death and inflammation in renal tubular cells, manifested by an increase in the expression of caspase-3, caspase-9, NFkB, iNOS, Kim-1 and decrease in Bcl-2 expression. These results were further supported by the histopathological examination of kidney. All these features of APAP toxicity were reversed by the co administration of HD. Therefore, our study favors the view that HD may be a useful modulator in alleviating APAP induced oxidative stress and toxicity. PMID- 22093919 TI - When warm air is what we need. PMID- 22093920 TI - Thinking outside the box: Aboriginal people's suggestions for conducting health studies with Aboriginal communities. AB - OBJECTIVES: Aboriginal people are under-represented in epidemiological research, largely due to past failures to engage and recruit Aboriginal communities, research fatigue and the use of culturally inappropriate methods. A qualitative study was undertaken in rural and urban Aboriginal communities in north-eastern and south-western Ontario to identify culturally congruent public health research methodologies. STUDY DESIGN: A qualitative participatory research study using focus group discussions. METHODS: This study employed a participatory research framework to elicit methodological suggestions for conducting public health research with Aboriginal communities during focus groups with healthcare providers from six diverse Aboriginal health organizations in Ontario, Canada. RESULTS: Continuing requests for participation in health research studies have led to community exhaustion. Discussions explored appropriate methods to obtain community approval and support for a study, the need for cultural sensitivity training for researchers, the value of conducting studies of interest and benefit to the community, advantages and disadvantages of qualitative and quantitative studies, the benefit of both Aboriginal and non-Aboriginal ethics reviews, the importance of safeguarding trusted information, types of incentives that may enhance study participation, suggestions to improve the collection of questionnaire information and biological specimens, how to resolve contentious issues and dissemination of study results. CONCLUSION: In order to successfully engage Aboriginal people in health studies, researchers need to build rapport with communities, have a community presence, be respectful and collaborative, utilize incentives, and employ flexible and adaptive methodologies of reasonable length. Oral interviews are preferred to self-completed information. The use of more mixed methods methodologies was suggested when quantitative data collection is necessary. Communities expect presentations about research findings. PMID- 22093921 TI - Successful liver transplantation following veno-arterial extracorporeal membrane oxygenation in a child with fulminant Wilson disease and severe pulmonary hemorrhage: a case report. AB - Massive pulmonary hemorrhage and other serious cardiopulmonary diseases in patients with fulminant hepatitis result not only in graft failure but also mortality after LT. ECMO is used to treat children with cardiorespiratory failure refractory to conventional intensive care. We describe a five-yr-old girl with genetically confirmed fulminant Wilson disease and severe pulmonary hemorrhage who underwent successful primary LT following veno-arterial ECMO. To our knowledge, this is the first report of successful primary LT in a patient using veno-arterial ECMO. The present case demonstrates that ECMO, as a bridging modality to LT, may be necessary to manage both massive pulmonary hemorrhage and possible graft loss because of hypoxemia. PMID- 22093922 TI - The development of verbal and visual working memory processes: a latent variable approach. AB - Working memory (WM) processing in children has been studied with different approaches, focusing on either the organizational structure of WM processing during development (factor analytic) or the influence of different task conditions on WM processing (experimental). The current study combined both approaches, aiming to distinguish verbal and visual processing in order to investigate WM development. We investigated recall performance under different task conditions in a sample of 5- to 13-year-olds, applying latent class regression analysis. In this analysis, we examined latent classes (subgroups) within the sample that differed in terms of processing type. The interpretations of the latent classes were validated internally using characteristics of the latent classes and externally using recall performance of words and figures. The results showed that children of different developmental stages used the same type of processing under the same conditions. However, due to developmental differences, their overall performances differed, showing groups of children who were successful in verbal or visual processing and groups of children who were not. This study shows and discusses the importance of disentangling the influence of task conditions from the influence of WM development when interpreting recall performance in children. PMID- 22093923 TI - Children's understanding of nonverbal expressions of pride. AB - To chart the developmental path of children's attribution of pride to others, we presented children (4 years 0 month to 11 years 11 months of age, N=108) with video clips of head-and-face, body posture, and multi-cue (both head-and-face and body posture simultaneously) expressions that adults consider to convey pride. Across age groups, 4- and 5-year-olds did not attribute pride to any expression presented, 6- and 7-year-olds attributed pride only to the multi-cue expression, and 8- to 11-year-olds attributed pride to both the head-and-face and multi-cue expressions. Children of all ages viewed the postural expression as anger rather than pride. Developmentally, pride is first attributed only when several cues are present and only later when a single cue (head-and-face) is present. PMID- 22093925 TI - [Bacteria against bacterium: the inhibitory effects of probiotics on Helicobacter pylori]. PMID- 22093924 TI - Nicotinic stimulation induces Tristetraprolin over-production and attenuates inflammation in muscle. AB - Cholinergic signaling suppresses inflammation in blood and brain and attenuates apoptosis in other tissues, but whether it blocks inflammation in skeletal muscle under toxicant exposure, injuries and diseases remained unexplored. Here, we report nicotinic attenuation of inflammation and alteration of apoptotic protein expression pattern in murine muscle tissue and cultured myotubes, involving the RNA-binding protein, Tristetraprolin, and the anti-apoptotic protein, Mcl-1. In muscles and C2C12 myotubes, cholinergic excitation by exposure to nicotine or the organophosphorous pesticide, Paraoxon, induced Tristetraprolin overproduction while reducing pro-inflammatory transcripts such as IL-6, CXCL1 (KC) and CCL2 (MCP-1). Furthermore, nicotinic excitation under exposure to the bacterial endotoxin LPS attenuated over-expression of the CCL2 and suppressed the transcriptional activity of NF-KB and AP-1. Tristetraprolin was essential for this anti-inflammatory effect of nicotine in basal conditions. However, its knockdown also impaired the pro-inflammatory response to LPS. Finally, in vivo administration of Paraoxon or recombinant Acetylcholinesterase, leading respectively to either gain or loss of cholinergic signaling, modified muscle expression of key mRNA processing factors and several of their apoptosis-related targets. Specifically, cholinergic imbalances enhanced the kinase activators of the Serine-Arginine splicing kinases, Clk1 and Clk3. Moreover, Paraoxon raised the levels of the anti-apoptotic protein, Mcl-1, through a previously unrecognized polyadenylation site selection mechanism, producing longer, less stable Mcl-1 mRNA transcripts. Together, our findings demonstrate that in addition to activating muscle function, acetylcholine regulates muscle inflammation and cell survival, and point to Tristetraprolin and the choice of Mcl-1 mRNA polyadenylation sites as potential key players in muscle reactions to insults. PMID- 22093926 TI - [Association analysis between dopamine D1 receptor gene and symptom quantitative trait of schizophrenia]. AB - OBJECTIVE: To explore the relationship between dopamine D1 receptor gene (DRD1) and symptom quantitative trait of schizophrenia. METHODS: Peripheral blood samples were collected from 211 schizophrenics and 247 healthy controls at our center. Five tag SNPs (single nucleotide polymorphisms) (rs4532, rs5326, rs2168631, rs6882300 & rs267418) within DRD1 gene were genotyped by TaqMan SNP genotyping assay. The positive and negative syndrome scale (PANSS) was used to quantify the phenotypes of schizophrenia. RESULTS: No significant differences existed in the frequencies of genotypes and alleles of DRD1 gene between the schizophrenics and normal controls (Ps > 0.05); strong linkage disequilibrium was observed between rs4532 and rs5326 (D' = 0.84); no significant difference of haplotypic distribution was identified between the patients and controls (Ps > 0.05); the patients with rs4532G allele had a higher negative subscale score than those without G allele (20.3 +/- 3.3 vs 18.2 +/- 3.9, P < 0.01). CONCLUSION: The rs4532 within DRD1 gene may be associated with negative symptom quantitative trait in schizophrenia. PMID- 22093927 TI - [Clinical efficacy of transcatheter renal arterial embolization plus cryoablation for medium and advanced renal carcinomas]. AB - OBJECTIVE: To investigate the clinical efficacy of transcatheter renal arterial embolization (TRAE) plus cryoablation in the treatment of medium and advanced stage renal carcinomas. METHODS: The patients with medium and advanced stage renal carcinomas were randomized into 2 groups: TRAE group (A, n = 53) and TRAE plus cryoablation group (B, n = 51) undergoing cryoablation 2 - 3 weeks after TRAE. A total of 128 tumors (8.7 +/- 3.2) (4.0 - 19.8) cm in diameter were detected. And the largest tumor in a specific patient with multiple lesions was selected for observation. At pre- and post-treatment, their clinical symptoms, kidney function and tumor diameters (computed tomography or magnetic resonance imaging) were observed. And their post-treatment profiles of tumor necrosis and survival were assessed. RESULTS: There was no difference in gender, age, size and Robson stage between two groups. The tumor necrosis of Group B was significantly higher than that of Group A (61% vs 35%, t = 6.784, P < 0.01). The median survival duration of Group B was significantly longer than that of Group A (24 vs 15 months, P < 0.05). There was no significant change of kidney function at pre- and post-treatment (P > 0.05). The quality-of-life scores improved at post treatment (P < 0.01). CONCLUSION: As compared with TRAE therapy alone, the combination of TRAE and cryoablation may improve the tumor necrosis rate and prolong the patient survival duration. PMID- 22093928 TI - [Correlation between severe preeclampsia and abnormal expression of long-chain fatty acid oxidative enzyme]. AB - OBJECTIVE: To explore the correlation between severe preeclampsia and abnormal expression of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD). METHODS: Serum free trophoblast cells cultured in vitro were divided into 4 groups under the stimulations of normal pregnancy serum (NP group), early onset severe preeclampsia serum (E-PE group), late onset severe preeclampsia serum (L-PE group) and HELLP (hemolysis, elevated liver enzymes & low platelets) syndrome serum (HELLP group) respectively. The expressions of mRNA and protein of LCHAD in trophoblast cells were detected by real-time polymerase chain reaction (PCR) and Western blot. RESULT: (1) Expression of LCHAD mRNA: the relative expressions of mRNA of LCHAD in NP, E-PE, L-PE and HELLP groups were 1.00 +/- 0.00, 3.08 +/- 0.22, 1.62 +/- 0.23 and 3.36 +/- 0.18 respectively. The relative expressions of LCHAD mRNA were significantly reduced in the E-PE, L-PE and HELLP groups versus the NP group (P < 0.05). Compared with the L-PE group, the gene expressions of LCHAD significantly decreased in the E-PE and HELLP groups (P < 0.05) while no significant difference was found between the E-PE and HELLP groups (P > 0.05). (2) Expression of LCHAD protein: the relative expressions of LCHAD protein were 4.94 +/- 0.02, 2.93 +/- 0.13, 4.14 +/- 0.06 and 2.80 +/- 0.09 in the NP, E-PE, L PE and HELLP groups respectively. The protein expressions of LCHAD were remarkably reduced in the E-PE, L-PE and HELLP groups versus the NP group (P < 0.05). The expressions of LCHAD protein remarkably decreased in the E-PE and HELLP groups versus the L-PE group (P < 0.05) while no significant difference was found between the E-PE and HELLP groups (P > 0.05). CONCLUSION: Long chain fatty acid oxidation is involved in the pathogenesis and development of preeclampsia. The expressions of LCHAD gene and protein are remarkably affected by early onset severe preeclampsia and HELLP syndrome. The interacting mechanism and influence between fatty acid oxidation and the development of preeclampsia are worth further exploring. PMID- 22093929 TI - [Prediction of chemoresistance in epithelial ovarian cancer by clinical factors]. AB - OBJECTIVE: To compare the clinical features and prognosis among patients with different chemosensitivity and determine the specific clinical influencing factors of chemotherapeutic resistance. METHODS: In references to the 2010 NCCN clinical practice guidelines on ovarian cancer and in accordance with the length of disease-free interval, 244 patients were divided into 3 groups: platinum resistant, partially sensitive and platinum-sensitive. The differences of clinical features, treatment and prognosis were compared among these 3 groups. RESULTS: The resistant, partially sensitive, sensitive rates to platinum-based chemotherapy were 23.4%, 13.5% and 63.1% respectively. Such factors as age, pathological type, primary tumor size. intraperitoneal chemotherapy and venous chemotherapy regimen had no effect on the responses to the combination platinum based chemotherapy. The platinum-resistant percentage of advanced stage patients without optimal cytoreductive surgery was higher (P < 0.01). The poorly differentiated rate of partially sensitive patients was higher than that of platinum-sensitive ones (P < 0.05). The CA125 level and lymph node metastasis rate of platinum-resistant patients were higher than those of platinum-sensitive patients (P < 0.05, P < 0.01). The 5-year survival rates of resistant, partially sensitive and sensitive patients were 9.5%, 38.4% and 81.9% respectively. There were statistics differences in overall survival and progression-free survival among the 3 groups (P < 0.01). CONCLUSION: Advanced ovarian cancer, poor differentiation, lymph node-positivity, CA125 rising above 1000 * 10(3) U/L and suboptimal cytoreductive surgery would lead to the occurrences of resistance or partially sensitivity. Clinical factors have some reference values for the prediction of resistance. But it is impossible to accurately determine chemoresistance. PMID- 22093930 TI - [A 2-year follow-up results of knee arthroscopic synovectomy plus disease modifying antirheumatic drugs for the treatment of rheumatoid arthritis]. AB - OBJECTIVE: To evaluate the clinical efficacy of knee arthroscopic synovectomy plus disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA) patients. METHODS: A total of 97 RA patients were treated with knee arthroscopic synovectomy plus DMARD after arthroscopy. The control group received only DMARD. The patients were assessed at pre-treatment and 1, 6, 12, 24 month post-treatment. Tender joint count, swollen joint count, morning stiffness, resting pain, patient global assessment, physician global assessment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and disease activity score (DAS) 28 were observed. RESULTS: Tender joint count, swollen joint count, morning stiffness, resting pain, patient global assessment, physician global assessment and DAS 28 score improved significantly at 1, 6 month post-treatment in the combined treatment group versus the control group. At 2 years post-treatment, there was still significant difference in DAS28 between two groups. CONCLUSION: The combined treatment of knee arthroscopic synovectomy and disease modifying antirheumatic drugs can control the disease activity of RA during an early period. And a long-term efficacy may be maintained. PMID- 22093931 TI - [Relationship between ROCK2 expression and clinicopathologic characteristics of esophageal squamous cell carcinoma]. AB - OBJECTIVE: To investigate the expression and relationship of Rho-associated protein kinase 2 (ROCK2) and clinical characteristics in esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemistry was performed to assay the expression of ROCK2 in tumor tissues and adjacent normal epithelium from 118 ESCC patients in tissue microarray. The relationship between ROCK2 level and clinicopathologic profiles such as age, gender, location, smoking, differentiation degree, T stage, lymph node metastasis and TNM stage were analyzed. RESULTS: The ROCK2 expression was up-regulated in 54 of 118 (45.76%) ESCC tissues. The up-regulated expression of ROCK2 was observed in 55.74% (34/61) ESCC tissues of patients under 61 years old. And it was significantly higher than that in 35.09% (20/57) of patients over 61 years old (chi(2) = 5.062, P = 0.024). In addition, the rate of up-regulation of ROCK2 was significantly higher in high grade differentiation group (58.70%, 27/46) than that in moderate-grade and low grade differentiation group (37.50%, 27/72) (chi(2) = 5.080, P = 0.024). CONCLUSION: The up-regulated expression of ROCK2 is correlated with patient age and differentiation grade of ESCC. PMID- 22093932 TI - [Pathological changes of rectal cancer after irinotecan, 5-fluorouracil or combined short-term radiotherapy]. AB - OBJECTIVE: To observe and evaluate the pathologic changes and curative effects of irinotecan (CPT-11), 5-fluorouracil (5-FU) and combined short-term radiotherapy before low-set rectal cancer operation so as to provide a theoretic basis for formulating a new effective adjuvant therapeutic regimen. METHODS: A total of 41 patients of low rectal cancer were treated with CPT-11, 5-FU therapy or CPT-11 plus 5-FU combined short-term radiotherapy from April 2002 to April 2009. They were divided into 2 groups according to different treatment schemes, including irinotecan group (n = 18) and irinotecan combined short-term radiotherapy group (n = 23). The pathologic changes before and after treatment were observed and the differences of two treatment approaches compared. RESULTS: Tumor cells had different degrees of degeneration and necrosis under microscope in two groups. Compared with computed tomographic findings before therapy, tumor sizes of two groups were reduced by an average of 33.1% (13.5 mm vs 20.2 mm) and 34.4% (12.8 mm vs 19.5 mm) respectively. Two groups were graded according to the RCRG (rectal cancer regression grade) score: RCRG1: 7 cases vs 18 cases, RCRG2: 4 cases vs 3 cases and RCRG3: 7 cases vs 2 cases. According to the pathologic evaluation standard, 3-degree necrosis, cell interstitial fibrosis and intimal thickening in vessels were observed in two groups: 7 cases vs 17 cases, 6 cases vs 17 cases and 3 cases vs 14 cases respectively (all P < 0.05). Five patients achieved complete pathological remission in the irinotecan combined short-term radiotherapy group. CONCLUSION: Based on the pathological changes and mitigation results after treatment, CPT-11 and 5-FU may be used as neoadjuvant drugs for rectal cancer. If the above two drugs can be used in combination with short-term radiation, the curative effect will be better. PMID- 22093933 TI - [Autologous bone grafting plus screw fixation for medial tibial defects in total knee arthroplasty]. AB - OBJECTIVE: To investigate the efficacy of autologous bone grafting plus screw fixation to reconstruct the medial tibial defects in total knee arthroplasty (TKA). METHODS: From November 2001 to November 2004, 46 patients (50 knees) with medial tibial bone defects underwent TKA at our hospital. There were 16 males (16 knees) and 30 females (34 knees). They included osteoarthritis (OA) (n = 35, 38 knees) and rheumatoid arthritis (RA) (n = 11, 12 knees). A total of 46 patients underwent three-dimensional CT (computed tomography) reconstruction to evaluate the tibial plateau defects after osteotomy. Single or double distal femoral osteotomic bone was used to reconstruct the bone defects with the hollow nail internal fixation. Another 80 TKA patients (86 knees) were randomly selected as the control group. The surgical outcome, lateral migration of tibial component and joint line elevation, etc. were analyzed and the follow-up knee society scores recorded. RESULTS: The patients were followed up for 6 to 9 years. Two patients were lost to follow-up and 1 died of myocardial infarction at 5 years post-TKA in the test group. In the last follow-up, 1 case suffered deep infections and all others had no prosthetic loosening. One case (1 knee) had resorption of wedge-shaped bone graft after 8 years. The remaining graft healed and there was no screw displacement. Medial platform split fracture occurred in 3 patients (3 knees) in the OA group. The quantity of distal femoral osteotomy, thickness of polyethylene insert, tibial implant size, joint line elevation and lateral migration of tibial base were greater than the other two groups (q test, P < 0.05). The pre- and post-operative KSS scores had significant differences in each group (F test, P < 0.05). But the same group showed no significant difference at 6, 9 years (q test, P > 0.05). CONCLUSION: As an easy and effective way of reconstructing the medial tibial bone defects, autologous bone grafting plus screw fixation can restore knee mechanical axis and stability. But in OA patients with tibial sclerosis, the complications of tibial component lateral migration, joint line elevation and splitting tibia fractures should be avoided during the reconstruction. PMID- 22093934 TI - [Digital simulation of unipedicular thoracolumbar vertebroplasty puncture]. AB - OBJECTIVE: To measure such operative parameters of unipedicular kyphoplasty as optimal entry point, angle and depth so as to provide rationales for its clinical management and formulate a standardized protocol for unipedicular vertebroplasty. METHODS: Ten dry thoracolumbar specimens were prepared for measurement. The entry and target points were defined according to the Roy-Camille method. A 3mm Kirschner wire was used to puncture and view in the anteroposterior and lateral aspects of radiography until a satisfying position. The outside oblique and upward oblique angles were measured on the radiographic pictures. After extraction, the depth of Kirschner wire was measured. The positions of entry point were changed and the largest upward oblique angle and largest declination angle measured on the radiographic pictures. RESULTS: For safe puncturing, as the outside oblique and upward oblique angles enlarged from T(11) to L(3), the length enlarged from T(11) to T(12) and L(1) to L(3). The accepted error was that the largest upward oblique angle and largest declination angle enlarged from T(11) to L(3). The alteration range for outside oblique angle was extremely narrow. CONCLUSION: The experimental results provide the guiding data for the operative management of unipedicular thoracolumbar vertebroplasty. If the pedicle is too small or the angle too narrow, the operative sophistication of vertebroplasty will be highly demanding. PMID- 22093935 TI - [Magnetic resonance imaging findings of lesions in limbic system related structures in general paresis of insane]. AB - OBJECTIVE: To analyze the magnetic resonance imaging (MRI) findings of lesions in the limbic system related structures in general paresis of insane (GPI) patients so as to explore its pathogenesis and provide a new MRI diagnostic method. METHODS: The clinical data and MRI findings of lesions in the limbic system related structures were retrospectively analyzed for a total of 31 GPI patients. The parameters were volume and signal abnormality. RESULTS: On MRI, structural abnormalities were found in amygdaloid body (n = 29), hippocampus (n = 28), insular lobe (n = 24), parahippocampal gyrus (n = 23), lenticular nucleus (n = 23), corpus callosum (n = 20), caudate nucleus (n = 11), hypothalamus (n = 10), anterior nucleus of thalamus (n = 10), cingulate gyrus (n = 8) and thalamus (n = 2). The frequent manifestations were atrophy, swelling, T2 hyperintensity in various structures and T2 hypointensity in lenticular nucleus. CONCLUSION: A frequent involvement of limbic system structures in GPI patients may be related with dementia and other psychiatric symptoms. Swelling and T2 hyperintensity of involved structures may be the characteristic MRI manifestations of GPI. PMID- 22093936 TI - [Relationship between methylenetetrahydrofolate reductase gene C677T polymorphism and susceptibility of ischemic stroke: a meta-analysis]. AB - OBJECTIVE: To evaluate the relationship between the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and the susceptibility of ischemic stroke among different ethnic populations. METHODS: The databases of MEDLINE, EMBASE, Cochrane Library and others were searched. And a total of 17 studies published in English between 2000 and October 2010 on the association of MTHFR gene C677T polymorphism with ischemic stroke were selected. A comprehensive quantitative analysis was performed by meta-analysis. RESULTS: The results showed that the pooled OR values of ischemic stroke with TT and CC genotype were 1.30 (95%CI: 1.11 to 1.52) and 0.88 (95%CI: 0.79 to 0.98) respectively. And when sub-grouped by ethnic populations, the Caucasians were more likely than other populations to suffer ischemic stroke. There was a low probability of publication bias. CONCLUSION: The presence of MTHFR TT gene is associated with an elevated risk of developing ischemic stroke, especially in Caucasians. PMID- 22093937 TI - [Effects of magnesium valproate on endocrine system and reproductive functions of female epileptics]. AB - OBJECTIVE: To explore the effects of valproate (VPA) on endocrine system in adolescent and reproductive female patients with epilepsy. METHODS: A total of 30 adolescent and reproductive female patients with a diagnosis of epilepsy at our hospital during July 2009 to March 2010 were recruited. All cases with magnesium VPA alone were included. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2), progesterone (P) and testosterone (T) were detected respectively at pre-therapy and 3, 6 and 12 months post-therapy. And the changes of menstruation and ovaries were recorded. RESULTS: The serum concentration of PRL was lower at 3 and 6 months post-therapy than that at pre-therapy. There was significant difference (P = 0.010 and 0.014). The serum concentration of E2 significantly decreased after a 3-month therapy of valproate (P < 0.05). While comparing the parameter's level between the initial test and at a 3, 6 and 12-month follow-up, the level of P significantly decreased in the later groups than that of the former one while the level of T showed a marked increase. The levels of FSH and LH were not significantly different at pre- and post-therapy. And 6 (20%) of them presented with menstrual dysfunctions and 3 (10%) polycystic ovary. CONCLUSION: The valproate therapy can not only cause the changes of endocrine system and hormonal levels, but also induce such endocrine dysfunction syndromes as menstrual suspension and polycystic ovary. It eventually causes polycystic ovary syndrome. PMID- 22093938 TI - [A study of microPET for assessing regional cerebral glucose metabolism and the expression of dopamine receptor type 2 in a rat model of Parkinson's disease]. AB - OBJECTIVE: To employ (18)F-fluoro-2-deoxyglucose ((18)F-FDG) and (3-N-[(11)C] methylspiperone)(11)C-NMSP microPET to assess the changes of regional cerebral glucose metabolism and the expression of dopamine receptor type 2 (DRD(2)) in a rat model of Parkinson's disease (PD). METHODS: A hemiparkinsonian model was established in rats by unilateral pretreatment with 6-hydroxydopamine (6-OHDA). At 2 weeks after 6-OHDA insult, (18)F-FDG and (11)C-NMSP microPET scan were performed to compare the differences of regional cerebral glucose metabolism and the expression of DRD(2) between the PD and control groups respectively. The immunohistochemical staining was used to detect the expression of tyrosine hydroxylase in two groups. RESULTS: In the PD model, the glucose metabolism rates were 88.2% +/- 2.2%, 94.5% +/- 4.5% and 96.2% +/- 5.8% respectively, in right striatum, hippocampus and sensorimotor cortex. And they were significantly lower than those in the control group [92.7% +/- 2.8% (P < 0.01), 98.9% +/- 3.9% (P < 0.01) & 102.8% +/- 2.1% (P < 0.01)]. The expression of DRD(2) in right striatum was significantly higher in the PD group than that in the control group (112.9% +/- 9.0% vs 102.3% +/- 1.4%, P < 0.01). CONCLUSION: In the PD rats, glucose metabolism decreases in injured side striatum, hippocampus and sensorimotor cortex while and the expression of DRD(2) increases in injured side striatum.(18)F-FDG and (11)C-NMSP microPET can effectively assess the regional cerebral glucose metabolism and the expression of DRD(2) in PD. They may serve as effective molecular imaging tools for an early diagnosis of PD. PMID- 22093939 TI - [Effects of PTHrP and Notch signaling on the proliferation of epiphysis stem cells]. AB - OBJECTIVE: To study the regulation of the proliferation of epiphysis stem cells by the PTHrP (parathyroid hormone related peptide) and Notch signaling systems. METHODS: An organ culture system of femurs of SD rat in 24 h after birth was employed. PTHrP (1 - 34) was used as the activator of the PTHrP signaling pathway and PTHrP (7 - 34) as the antagonist of PTH (parathyroid hormone)-receptor. For Notch signaling system, Jagged1/Fc was used as the activator and DAPT as its inhibitor. The femurs were cultured in DMEM (Dulbecco's modified Eagle's medium)/F12 medium while phosphate buffered saline was used for the control groups. Hematoxylin and eosin staining and bromodeoxyuridine analysis were used to analyze the length of the epiphysis stem cells zone and the proliferation of epiphysis stem cells. The expression of NICD (Notch intra-cellular domain) and Jagged1 were analyzed by immunohistochemistry. The epiphysis stem cells were transfected with the lentiviral vectors with rat PTHrP gene overexpression or inhibition properties, the cells transfected with the PGC-GFP-lentivirus or NC GFP-lentivirus were used as control. Western blot was employed to detect the expression of NICD and Jagged1 genes. RESULTS: PTHrP (1 - 34) and Jagged1/Fc could dramatically elevate the rate of epiphysis stem cells zone by the whole growth plate length measurement while PTHrP (7 - 34) and DAPT could decrease the rate. Brdu analysis also showed that the number of proliferative epiphysis stem cells could be up-regulated by the PTHrP (1 - 34) or Jagged1/Fc signaling. By contrast, the treatment with PTHrP (7 - 34) or DAPT reduced the number of proliferative epiphysis stem cells. Immunohistochemistry and Western blot showed a significantly elevated expression of NICD and Jagged1 when PTHrP signaling was activated while a reductive expression of NICD and Jagged1 when PTHrP signaling was inactivated. CONCLUSION: Both of PTHrP and Notch signaling system could promote the proliferation of epiphysis stem cells. And the PTHrP signaling can stimulate Notch signaling to promote the proliferation of epiphysis stem cells. PMID- 22093940 TI - [Generation of antitumor response against hepatocellular carcinoma by in vitro transduction of dendritic cells with adeno-associated virus expressing alpha fetoprotein]. AB - OBJECTIVE: To investigate the generation of antitumor response against hepatocellular carcinoma by in vitro transduction of dendritic cells (DC) with recombinant adeno-associated virus expressing alpha-fetoprotein (rAAV-AFP). METHODS: Peripheral blood mononuclear cells were isolated from healthy volunteers. Adherent peripheral blood mononuclear cells were transduced with AAV AFP and cultured in the presence of granulocyte macrophage colony stimulating factor and interleukin-4 to generate dendritic cells. MTS assay was used to measure the ability of DC transduced with AAV-AFP (AAV-AFP + DC) to stimulate the proliferation of T cell. The phenotype and AFP protein expression of DC and the secretion of IFN (interferon)-gamma and IL (interleukin)-4 by T cells were detected by flow cytometry. The killing efficacy of cytotoxic T lymphocytes (CTL) activated by AAV-AFP + DC against AFP positive hepatocellular carcinoma cell lines was detected by lactate dehydrogenase (LDH) release assay. RESULTS: AAV-AFP + DC expressed HLAI (97.12%), HLAII (97.32%), CD80 (38.94%), CD83 (60.84%) and CD86 (98.14%). AFP was secreted by 81.2% of AAV-AFP + DC. And it could stimulate effectively the proliferation of T cell. 19.84% of CD4(+)T cells and 18.65% of CD8(+)T cells activated by AAV-AFP + DC produced IFN-gamma but not IL-4 and showed distinct killing activities against AFP positive hepatocellular carcinoma cell lines HepG2 (56.45%) and BEL7402 (78.84%). CONCLUSION: AAV-AFP + DC can elicit distinct antitumor responses against AFP positive hepatocellular carcinoma cell lines so as to provide a basis for further researches on the clinical application of AAV-AFP + DC in the treatment of hepatocellular carcinoma. PMID- 22093941 TI - Method comparison of dipeptidyl peptidase IV activity assays and their application in biological samples containing reversible inhibitors. AB - BACKGROUND: Dipeptidyl peptidase IV (DPPIV, DPP4) is a serine protease that releases N-terminal dipeptides. It is a validated drug target for type 2 diabetes and DPPIV inhibitors are currently evaluated for other therapeutic applications. Various assays are used for DPPIV activity measurements in biological samples. Highly sensitive methods are needed to measure also very low activities in inhibited samples. METHODS: Here, the three most extensively used substrates to quantify DPPIV activity are compared using in-house methods. A luminescent kit was also included. In addition, one of the in-house fluorometric assays was elaborated for use in biological samples containing reversible DPPIV inhibitors to estimate residual DPPIV activity which is usually underestimated due to sample dilution. RESULTS: The in-house methods showed a good precision, linearity and specificity. Both fluorometric substrates had a 10-fold higher sensitivity compared to the colorimetric assay. The luminescent kit was found to be the most sensitive. CONCLUSIONS: All three in-house methods can be used to measure DPPIV activity in non-inhibited biological samples. The more sensitive fluorometric assays are recommended when sample volumes are limited or when using inhibited samples. The elaborated fluorometric method can be used to estimate the residual in vivo DPPIV activity in inhibitor treated subjects. PMID- 22093942 TI - Corin in clinical laboratory diagnostics. AB - Corin is a transmembrane serine protease identified in the heart, where it converts natriuretic peptides from inactive precursors to mature active forms. Studies in animal models and patients with hypertension and heart disease demonstrate that corin is critical in maintaining normal blood pressure and cardiac function. Like many proteolytic enzymes, corin expression and activity are regulated. Cell biology experiments indicate that transcriptional control, intracellular protein trafficking, cell surface targeting, zymogen activation and ectodomain shedding are important mechanisms in regulating corin expression and activity in the heart. More recently, soluble corin was detected in human blood and its levels were found to be reduced in patients with heart failure (HF). These findings indicate that corin deficiency may be involved in the pathogenesis of HF and suggest that soluble corin may be used as a biomarker for the disease. In this review, we describe the function and regulation of corin and discuss recent studies of soluble corin in human blood and its potential use as a biomarker for HF. PMID- 22093943 TI - Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03). AB - PURPOSE: Patients with brain metastases (BM) rarely survive longer than 6months and are commonly excluded from clinical trials. We explored two combined modality regimens with novel agents with single agent activity and radiosensitizing properties. PATIENTS AND METHODS: In this randomised phase II trial patients with BM from NSCLC were randomly assigned to 30Gy WBRT with either concomitant gefitinib (GFT) 250mg/day continuously or temozolomide (TMZ) 75mg/m(2) for 21/28days. The primary end-point was overall survival, with quality of life and cognitive function as secondary end-points. RESULTS: We enrolled 59 patients (GFT 16, TMZ 43), and 56 patients have died, mainly (80%) from disease progression. Four patients succumbed complications of the disease or corticosteroids (intestinal perforation (2), CNS haemorrhage and pulmonary emboli). Median overall survival in the gefitinib arm was 6.3months (95% CI 2.1-14.6), and 4.9months (95% CI 2.3-5.6) in TMZ treated patients. Fatigue was the main complaint. CONCLUSIONS: No relevant toxicity with those therapeutic regimens was observed. Fatal outcome in three patients may have been related to corticosteroids. Cognitive function improved during treatment. However, median overall survival for all patients was only 4.9months (95% CI 2.3-5.7) and 1-year survival 25.4% (95% CI 15.4-37.0%). PMID- 22093944 TI - Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report. AB - PURPOSE: To examine whether three cycles of a low-intensity chemotherapy consisting of cyclophosphamide [500 mg/m(2) - day 1], vinblastine [6 mg/m(2) - days 1 and 8] and prednisolone [40 mg/m(2) - days 1-7] (CVP) is safe and therapeutically effective in children and adolescents with early stage nodular lymphocyte predominant Hodgkin lymphoma [nLPHL]. PATIENTS AND METHODS: Fifty-five children and adolescents with early stage nLPHL [median age 13 years, range 4-17 years] diagnosed between June 2005 and October 2010 in the UK and France are the subjects of this report. Staging investigations included conventional cross sectional as well as 18 fluro-deoxyglucose [FDG] PET imaging. Histology was confirmed as nLPHL by an expert pathology panel. RESULTS: Of the 45 patients, who received CVP as first line treatment, 36 [80%, 95% Confidence Interval [CI]: (68; 92)] either achieved a complete remission [CR] or CR unconfirmed [CRu], the remaining nine patients achieved a partial response. All nine subsequently achieved CR with salvage chemotherapy [n=7] or radiotherapy [n=2]. Ten patients received CVP at relapse after primary treatment that consisted of surgery alone and all achieved CR. To date, only three patients have relapsed after CVP chemotherapy and all had received CVP as first line treatment at initial diagnosis. The 40-month freedom from treatment failure and overall survival for the entire cohort were 75.4% (SE +/- 6%) and 100%, respectively. No significant early toxicity was observed. CONCLUSIONS: Our results show that CVP is an effective chemotherapy regimen in children and adolescents with early stage nLPHL that is well tolerated with minimal acute toxicity. PMID- 22093945 TI - How many deaths would be avoidable if socioeconomic inequalities in cancer survival in England were eliminated? A national population-based study, 1996 2006. AB - AIM: Inequalities in survival between rich and poor have been reported for most adult cancers in England. This study aims to quantify the public health impact of these inequalities by estimating the number of cancer-related deaths that would be avoidable if all patients were to have the same cancer survival as the most affluent patients. METHODS: National Cancer Registry data for all adults diagnosed with one of 21 common cancers in England were used to estimate relative survival. We estimated the number of excess (cancer-related) deaths that would be avoidable within three years after diagnosis if relative survival for patients in all deprivation groups was as high as the most affluent group. RESULTS: For patients diagnosed during 2004-2006, 7122 of the 64,940 excess deaths a year (11%) would have been avoidable if three-year survival for all patients had been as high as in the most affluent group. The annual number of avoidable deaths fell from 8435 (13%) a year for patients diagnosed during 1996-2000. Over 60% of the total number of avoidable deaths occurred within six months after diagnosis and approximately 70% occurred in the two most deprived groups. CONCLUSION: The downward trend in the annual number of avoidable deaths reflects more an improvement in survival in England overall, rather than a narrowing of the deficit in cancer survival between poor and rich. The lack of any substantial change in the percentage of avoidable excess deaths highlights the persistent nature of the deficit in survival between affluent and deprived groups. PMID- 22093946 TI - Targeted agents: how to select the winners in preclinical and early clinical studies? AB - There has been a significant shift within oncology drug development away from empiric screening of cytotoxic compounds to the era of genomics and molecularly targeted agents. The drug development process is evolving with greater emphasis on proof-of-mechanism studies in both preclinical and early clinical development. The Methodology for the Development of Innovative Cancer Therapies (MDICT) Task Force, established as a forum for academic and pharmaceutical leaders to discuss methodological issues in targeted anticancer therapy development, met in March 2010 to review what were the minimal data required to make appropriate decisions about moving new targeted cancer agents from late preclinical development into phase I and from phase I into phase II trials. A number of specific questions were posed, and responses to each developed through survey, literature review and discussion at the face to face meeting of the MDICT Task Force. Consensus emerged around the necessity to demonstrate proof-of-mechanism and obtain information on key pharmacokinetic aspects of drug behaviour in late preclinical and early clinical trials. However, controversy remains on the extent of in vivo anti tumour efficacy required to support clinical development of targeted agents. A systematic review of the data in this area would be informative. Further, while objective response in phase I trials may be a favourable signal about the potential activity of a new agent, debate exists around the weight that should be placed on the observation of stable disease or functional imaging changes in driving drug development decisions in the absence of observing either responses or convincing pharmacodynamic data in phase I. MDICT made a number of recommendations that may aid in future development of targeted agents. PMID- 22093947 TI - Baropodometry on women suffering from chronic pelvic pain--a cross-sectional study. AB - BACKGROUND: Previous studies have associated chronic pelvic pain with a stereotyped pattern of movement and posture, lack of normal body sensations, a characteristic pain distribution. We aimed at evaluating if these postural changes are detectable in baropodometry results in patients with chronic pelvic pain. METHODS: We performed a prospective study in a university hospital. We selected 32 patients suffering from chronic pelvic pain (study group) and 30 women without this pathology (regular gynecological work out--control group). Pain scores and baropodometric analysis were performed. RESULTS: As expected, study group presented higher pain scores than control group. Study and control groups presented similar averages for the maximum pressures to the left and right soles as well as soles supports in the forefeet and hind feet. Women suffering from chronic pelvic pain did not present differences in baropodometric analysis when compared to healthy controls. CONCLUSIONS: This data demonstrates that postural abnormalities resulting from CPP could not be demonstrated by baropodometric evaluation. Other postural measures should be addressed to evaluate pelvic pain patients. PMID- 22093948 TI - Androgen deprivation therapy before radical prostatectomy is associated with poorer postoperative erectile function outcomes. PMID- 22093949 TI - Incidental encoding of goal irrelevant information is associated with insufficient engagement of the dorsal frontal cortex and the inferior parietal cortex. AB - Previous studies have shown that goal-irrelevant distractors are incidentally encoded into long-term memory. Neuroimaging studies have suggested that the medial temporal and visual association regions are involved in incidental encoding of goal-irrelevant information. However, few studies have investigated prefrontal/parietal influence during the incidental encoding. The present study performed whole brain analysis to identify the brain regions involved in the incidental encoding of goal-irrelevant information. A face working memory (WM) task was administered with insertion of face distractors during the delay period. Following the WM task, a surprise recognition task was given in an MRI scanner. Recognition rate of distractors was higher than that of novel fillers. Recognition time was also faster in distractors than in novel fillers. Neuroimaging results showed less activation to distractors subsequently remembered than those forgotten in the middle and superior frontal regions and the lateral inferior parietal lobe including the angular gyrus and the temporoparietal regions. However, the left anterior hippocampus and the right fusiform gyrus showed greater activation to distractors subsequently remembered. Those findings suggest that insufficient engagement of the dorsal frontal cortex which regulates attentional control and the inferior parietal lobe which functions to reorient attention may allow goal-irrelevant information access to working memory and to be encoded into long-term memory. PMID- 22093950 TI - Pantoea clinical isolates cannot be accurately assigned to species based on metabolic profiling. PMID- 22093951 TI - Effect of dornase alfa on inflammation and lung function: potential role in the early treatment of cystic fibrosis. AB - Dornase alfa has been shown to reduce markers of inflammation and neutrophil associated metalloproteinases in cystic fibrosis (CF), suggesting a potential benefit from use of this therapy early in the disease. However, observational studies indicate that dornase alfa is often reserved for "sicker" patients. A 2 year, early intervention study of dornase alfa in CF patients with early lung disease demonstrated significant improvements in lung function and risk of exacerbation compared to placebo. A more recent analysis, using the database of the large observational Epidemiologic Study of Cystic Fibrosis (ESCF), found that initiation of dornase alfa has the potential to alter the course of CF by decreasing the rate of lung function decline in children and adults. These encouraging results, possibly linked to indirect effects on inflammation, suggest a greater role for dornase alfa therapy in the early treatment of CF, where it may help preserve lung function and potentially extend survival. PMID- 22093953 TI - Hypertrophy hypothesis as an alternative explanation of the phenomenon of replicative aging of yeast. AB - This paper summarizes numerous arguments demonstrating that the hypothesis of accumulation of the senescence factor, which was the basis for introducing yeast to the group of model organisms of gerontology, finds no experimental support. Among several candidates for the role of the causative agents of replicative aging, only one - hypertrophy - always accompanies symptoms of aging, not only in Saccharomyces cerevisiae, but also in Schizosaccharomyces pombe. PMID- 22093952 TI - Functional characterization and analgesic effects of mixed cannabinoid receptor/T type channel ligands. AB - BACKGROUND: Both T-type calcium channels and cannabinoid receptors modulate signalling in the primary afferent pain pathway. Here, we investigate the analgesics activities of a series of novel cannabinoid receptor ligands with T type calcium channel blocking activity. RESULTS: Novel compounds were characterized in radioligand binding assays and in vitro functional assays at human and rat CB1 and CB2 receptors. The inhibitory effects of these compounds on transient expressed human T-type calcium channels were examined in tsA-201 cells using standard whole-cell voltage clamp techniques, and their analgesic effects in response to various administration routes (intrathecally, intraplantarly, intraperitoneally) assessed in the formalin model. A series of compounds were synthesized and evaluated for channel and receptor activity. Compound NMP-7 acted as non-selective CB1/CB2 agonist while NMP4 was found to be a CB1 partial agonist and CB2 inverse agonist. Furthermore, NMP-144 behaved as a selective CB2 inverse agonist. All of these three compounds completely inhibited peak Cav3.2 currents with IC50 values in the low micromolar range. All compounds mediated analgesic effects in the formalin model, but depending on the route of administration, could differentially affect phase 1 and phase 2 of the formalin response. CONCLUSIONS: Our results reveal that a set of novel cannabinioid receptor ligands potently inhibit T-type calcium channels and show analgesic effects in vivo. Our findings suggest possible novel means of mediating pain relief through mixed T type/cannabinoid receptor ligands. PMID- 22093954 TI - Gemcitabine and tamoxifen-loaded liposomes as multidrug carriers for the treatment of breast cancer diseases. AB - The effects of a lipid composition on the physico-chemical and technological properties of a multidrug carrier (MDC) containing both gemcitabine (GEM) and tamoxifen (TMX), as well as its in vitro antitumoral activity on different breast cancer cell lines, were investigated. In particular, the following three different liposomal formulations were prepared: DPPC/Chol/DSPE-mPEG2000 (6:3:1 molar ratio, formulation A), DPPC/Chol/DOTAP (6:3:1 molar ratio, formulation B) and DPPC/Chol/DPPG (6:3:1 molar ratio, formulation C). The colloidal systems were obtained by the TLE technique and the extrusion process allowed us to obtain vesicles having mean sizes of 150-200 nm, while the surface charges varied between 50 mV and -30 mV. Formulation A showed the best encapsulation efficiency between the two compounds and the presence of TMX influenced the release profile of GEM (hydrophilic compound) as a consequence of its effect on the fluidity of the bilayer. An MDC of formulation A was used to effectuate the in vitro cytotoxicity experiments (MTT-test) on MCF-7 and T47D cells. The liposomal MDC provided the best results with respect to the single drug tested in the free form or entrapped in the same liposomal formulation. The CLSM experiments showed a great degree of cell interaction of liposomal MDC after just 6h. PMID- 22093955 TI - Preparation and evaluation of a novel gastric floating alginate/poloxamer inner porous beads using foam solution. AB - In the present study, a simple and rapid method was developed to prepare a novel kind of inner-porous floating beads. The beads were prepared by dripping the foam solution into CaCl(2) solution using disposable syringe needle, where the foam solution consisting numerous of microbubbles with poloxamer 188 as foaming agents, alginate as foaming stablizer. Foamability and foam stability of different polymer ratios were evaluated. The SEM cross-section pictures of the beads showed that the beads were inner-porous and composed of bubbles with very thin wall bubbles stacked together. The visual observation result and the resultant-weight method confirmed that the floating beads showed good buoyancy, most beads could float in the stomach for more than 6 h. The floating beads release behavior in vitro showed that drug release from the beads in a sustained release fashion for 10 h. Gamma scintigraphic images and pharmacokinetic studies in vivo showed that the beads can retained in the stomach for over 6 h and can improve the bioavailability of drug with narrow absorption window. PMID- 22093956 TI - Anti-tumor activity of all-trans retinoic acid-incorporated glycol chitosan nanoparticles against HuCC-T1 human cholangiocarcinoma cells. AB - The aim of this study is to investigate antitumor activity of all-trans retinoic acid (RA)-incorporated glycol chitosan (GC) nanoparticles. RA-incorporated GC nanoparticles were prepared by electrostatic interaction between RA and amine group of GC. RA-incorporated GC nanoparticles have spherical shape and their particle size was 317 +/- 34.5 nm. They were simply reconstituted into aqueous solution without changes of intrinsic properties. RA-incorporated GC nanoparticles were evidently inhibited the proliferation of HuCC-T1 cholangiocarcinoma cells at higher than 20 MUg/ml of RA concentration while empty GC vegicles did not affect to the viablity of tumor cells. Apoptosis and necrosis analysis of tumor cells with treatment of RA or RA-incorporated GC nanoparticles also supported these results. Invasion test using Matrigel also showed that invasion of tumor cells was significantly inhibited at higher than 20 MUg/ml of RA concentration. Wound healing assay also showed that RA-incorporated GC nanoparticles were inhibited migration of tumor cells as similar to RA itself. Our results suggested that RA-incorporated GC nanoparticles is a promising vehicles for RA delivery to HuCC-T1 cholangiocarcinoma cells. PMID- 22093958 TI - Evaluation of high frequency ultrasound methods and contrast agents for characterising tumor response to anti-angiogenic treatment. AB - PURPOSE: To compare non-enhanced and contrast-enhanced high-frequency 3D Doppler ultrasound with contrast-enhanced 2D and 3D B-mode imaging for assessing tumor vascularity during antiangiogenic treatment using soft-shell and hard-shell microbubbles. MATERIALS AND METHODS: Antiangiogenic therapy effects (SU11248) on vascularity of subcutaneous epidermoid-carcinoma xenografts (A431) in female CD1 nude mice were investigated longitudinally using non-enhanced and contrast enhanced 3D Doppler at 25 MHz. Additionally, contrast-enhanced 2D and 3D B-mode scans were performed by injecting hard-shell (poly-butyl-cyanoacrylate-based) and soft-shell (phospholipid-based) microbubbles. Suitability of both contrast agents for high frequency imaging and the sensitivity of the different ultrasound methods to assess early antiangiogenic therapy effects were investigated. Ultrasound data were validated by immunohistology. RESULTS: Hard-shell microbubbles induced higher signal intensity changes in tumors than soft-shell microbubbles in 2D B-mode measurements (424 +/- 7 vs. 169 +/- 8 A.U.; p<0.01). In 3D measurements, signals of soft-shell microbubbles were hardly above the background (5.48 +/- 4.57 vs. 3.86 +/- 2.92 A.U.), while signals from hard-shell microbubbles were sufficiently high (30.5 +/- 8.06 A.U). Using hard-shell microbubbles 2D and 3D B-mode imaging depicted a significant decrease in tumor vascularity during antiangiogenic therapy from day 1 on. Using soft-shell microbubbles significant therapy effects were observed at day 4 after therapy in 2D B-mode imaging but could not be detected in the 3D mode. With non-enhanced and contrast-enhanced Doppler imaging significant differences between treated and untreated tumors were found from day 2 on. CONCLUSION: Hard-shell microbubble enhanced 2D and 3D B-mode ultrasound achieved highest sensitivity for assessing therapy effects on tumor vascularisation and were superior to B-mode ultrasound with soft-shell microbubbles and to Doppler imaging. PMID- 22093957 TI - Integration of a laterally acquired gene into a cell network important for growth in a strain of Vibrio rotiferianus. AB - BACKGROUND: Lateral Gene Transfer (LGT) is a major contributor to bacterial evolution and up to 25% of a bacterium's genome may have been acquired by this process over evolutionary periods of time. Successful LGT requires both the physical transfer of DNA and its successful incorporation into the host cell. One system that contributes to this latter step by site-specific recombination is the integron. Integrons are found in many diverse bacterial Genera and is a genetic system ubiquitous in vibrios that captures mobile DNA at a dedicated site. The presence of integron-associated genes, contained within units of mobile DNA called gene cassettes makes up a substantial component of the vibrio genome (1 3%). Little is known about the role of this system since the vast majority of genes in vibrio arrays are highly novel and functions cannot be ascribed. It is generally regarded that strain-specific mobile genes cannot be readily integrated into the cellular machinery since any perturbation of core metabolism is likely to result in a loss of fitness. RESULTS: In this study, at least one mobile gene contained within the Vibrio rotiferianus strain DAT722, but lacking close relatives elsewhere, is shown to greatly reduce host fitness when deleted and tested in growth assays. The precise role of the mobile gene product is unknown but impacts on the regulation of outermembrane porins. This demonstrates that strain specific laterally acquired mobile DNA can be integrated rapidly into bacterial networks such that it becomes advantageous for survival and adaptation in changing environments. CONCLUSIONS: Mobile genes that are highly strain specific are generally believed to act in isolation. This is because perturbation of existing cell machinery by the acquisition of a new gene by LGT is highly likely to lower fitness. In contrast, we show here that at least one mobile gene, apparently unique to a strain, encodes a product that has integrated into central cellular metabolic processes such that it greatly lowers fitness when lost under those conditions likely to be commonly encountered for the free living cell. This has ramifications for our understanding of the role mobile gene encoded products play in the cell from a systems biology perspective. PMID- 22093960 TI - Patch valvuloplasty in patients with posterior chordae rupture. PMID- 22093959 TI - Bone and mineral metabolism and fibroblast growth factor 23 levels after kidney donation. AB - BACKGROUND: Living kidney donation offers a unique setting to study changes in phosphate and vitamin D homeostasis attributable to mild isolated decreases in estimated glomerular filtration rate (eGFR). STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 198 living kidney donors and 98 nondonor controls from 9 transplant centers across 3 countries. For donors, median time after donation was 5.3 years. At assessment, donors had a lower eGFR than controls (73 vs 98 mL/min/1.73 m(2)). PREDICTOR: Living kidney donation (mildly decreased eGFR). OUTCOMES: Biochemical markers of chronic kidney disease-mineral and bone disorder. MEASUREMENTS: Serum creatinine, total serum calcium, serum and urine inorganic phosphate, plasma intact parathyroid hormone, serum calcidiol and calcitriol, renal fractional excretion of inorganic phosphate, and intact serum fibroblast growth factor 23 (FGF-23). RESULTS: Serum FGF-23 levels were significantly higher in donors (38.1 vs 29.7 pg/mL; P < 0.001). For every 10 mL/min/1.73 m(2) decrease in eGFR, FGF-23 level was higher by 3.2 (95% CI, 2.0 4.4) pg/mL. Compared with controls, donors showed higher renal tubular fractional excretion of inorganic phosphate (17.8% vs 12.3%; P < 0.001), lower serum phosphate (0.97 vs 1.02 mmol/L; P = 0.03), and lower serum calcitriol values (63 vs 77 pmol/L; P < 0.001). Serum calcium levels were not significantly different between the 2 groups. Plasma intact parathyroid hormone levels were significantly higher in donors (5.7 vs 5.0 pmol/L; P = 0.03), but were not correlated with FGF 23 or calcitriol levels. LIMITATIONS: Enrollment of a small proportion of past donors at participating centers; assessment of only postdonation values; unable to assess seasonal variation or other temporal patterns in biochemical markers; assessment of kidney function was based on eGFR, not measured GFR. CONCLUSIONS: The FGF-23 pathway may be activated in living kidney donors who show early biochemical changes compatible with chronic kidney disease-mineral and bone disorder. Whether these changes influence bone mineral density and fracture rates warrants consideration. PMID- 22093961 TI - Long-term outcome of sirolimus-eluting vs bare-metal stent in the setting of acute myocardial infarction: 5-year results of the SESAMI trial. AB - BACKGROUND: few long-term randomized data on safety and effectiveness of sirolimus-eluting stent (SES) in the ST-segment elevation myocardial infarction (STEMI) setting are available. The aim of the present investigation was to evaluate the 5-year clinical outcome of SES vs bare-metal stent (BMS) implantation in patients with STEMI. METHODS: 320 STEMI patients were randomized to receive SES or BMS. The primary end-point was the incidence of target vessel failure (TVF) at 5-year follow-up. The secondary end-points were the rate of target lesion revascularization (TLR), major adverse cardiovascular events (MACE), death or non-fatal MI and stent thrombosis (ST). Event rates from 1 to 5 years in patients undergoing TLR and those TLR free at 1 year were also investigated. RESULTS: The 5-year survival rate free from TVF and TLR was significantly higher in the SES than in the BMS group (85% vs 76% p=0.038; 92% vs 85% p=0.045, respectively). The lower incidence of adverse events was achieved in the first year of follow-up. The cumulative incidence of MACE, death or non-fatal MI and ST was comparable in the 2 groups at 5-year follow-up. Moreover death or MI incidence was 5% in the patients who did not experience TLR within 1-year and 16% in those who experience TLR in the same period (p=0.033). Predictors of death or MI during 5-year follow-up were TLR within 1 year (OR 3.4, 95% CI 1.1-10.1; p=0.04) and small vessels treatment (OR 4.8 95% CI 1.7-13.0; p=0.002). CONCLUSIONS: The clinical benefits of SES are maintained up to 5years without safety concerns. PMID- 22093962 TI - Transradial extra deep coronary intubation with a guide catheter for direct thromboaspiration in acute myocardial infarction. PMID- 22093964 TI - No evidence for an association of AB0 blood group and manifestation of thrombotic microangiopathies. PMID- 22093963 TI - Overexpression of cAMP-response element modulator causes abnormal growth and development of the atrial myocardium resulting in a substrate for sustained atrial fibrillation in mice. AB - BACKGROUND AND METHODS: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. The substrate of AF is composed of a complex interplay between structural and functional changes of the atrial myocardium often preceding the occurrence of persistent AF. However, there are only few animal models reproducing the slow progression of the AF substrate to the spontaneous occurrence of the arrhythmia. Transgenic mice (TG) with cardiomyocyte directed expression of CREM-IbDeltaC-X, an isoform of transcription factor CREM, develop atrial dilatation and spontaneous-onset AF. Here we tested the hypothesis that TG mice develop an arrhythmogenic substrate preceding AF using physiological and biochemical techniques. RESULTS: Overexpression of CREM-IbDeltaC-X in young TG mice (<8weeks) led to atrial dilatation combined with distension of myocardium, elongated myocytes, little fibrosis, down-regulation of connexin 40, loss of excitability with a number of depolarized myocytes, atrial ectopies and inducibility of AF. These abnormalities continuously progressed with age resulting in interatrial conduction block, increased atrial conduction heterogeneity, leaky sarcoplasmic reticulum calcium stores and the spontaneous occurrence of paroxysmal and later persistent AF. This distinct atrial remodelling was associated with a pattern of non-regulated and up-regulated marker genes of myocardial hypertrophy and fibrosis. CONCLUSIONS: Expression of CREM-IbDeltaC-X in TG hearts evokes abnormal growth and development of the atria preceding conduction abnormalities and altered calcium homeostasis and the development of spontaneous and persistent AF. We conclude that transcription factor CREM is an important regulator of atrial growth implicated in the development of an arrhythmogenic substrate in TG mice. PMID- 22093965 TI - Controversies surrounding the clinical potential of cinnamon for the management of diabetes. AB - Obesity levels have increased significantly in the past five decades and are predicted to continue rising, resulting in important health implications. In particular, this has translated to an increase in the occurrence of type II diabetes mellitus (T2D). To alleviate associated problems, certain nutraceuticals have been considered as potential adjuncts or alternatives to conventional prescription drugs. Cinnamon, a commonly consumed spice originating from South East Asia, is currently being investigated as a potential preventative supplement and treatment for insulin resistance, metabolic syndrome and T2D. Extensive in vitro evidence has shown that cinnamon may improve insulin resistance by preventing and reversing impairments in insulin signalling in skeletal muscle. In adipose tissue, it has been shown that cinnamon increases the expression of peroxisome proliferator-activated receptors including, PPARgamma. This is comparable to the action of commonly used thiazolinediones, which are PPAR agonists. Studies have also shown that cinnamon has potent anti-inflammatory properties. However, numerous human clinical trials with cinnamon have been conducted with varying findings. While some studies have showed no beneficial effect, others have indicated improvements in cholesterol levels, systolic blood pressure, insulin sensitivity and postprandial glucose levels with cinnamon. However, the only measurement consistently improved by cinnamon consumption is fasting glucose levels. While it is still premature to suggest the use of cinnamon supplementation based on the evidence, further investigation into mechanisms of action is warranted. Apart from further characterization of genetic and epigenetic changes in model systems, systematic large-scale clinical trials are required. In this study, we discuss the mechanisms of action of cinnamon in the context of T2D and we highlight some of the associated controversies. PMID- 22093966 TI - Detection, localisation and characterisation of prostate cancer by prostate HistoScanning(TM). AB - What's known on the subject? and What does the study add? Prostate cancer is one of the few solid-organ cancers in which imaging is not used in the diagnostic process. Novel functional magnetic resonance imaging techniques offer promise but may not be cost-effective. Prostate HistoScanning(TM) (PHS) is an ultrasound based tissue characterisation technique that has previously shown encouraging results in the detection of clinically significant prostate cancer. The present study reports on the open 'unblinded' phase of a European multicentre study. The prospective 'blind' phase is currently in progress and will determine the value of PHS in a robust fashion overcoming many of the biases inherent in evaluating prostate imaging. OBJECTIVE: To evaluate the ability of prostate HistoScanning(TM) (PHS) an ultrasound (US)-based tissue characterization application, to detect cancer foci by correlating results with detailed radical prostatectomy (RP) histology. PATIENT AND METHODS: In all, 31 patients with organ confined prostate cancer, diagnosed on transrectal biopsies taken using US guidance, and scheduled for RP were recruited from six European centres. Before RP three-dimensional (3D) US raw data for PHS analysis was obtained. Histology by Bostwick Laboratories (London) examined sections obtained from whole mounted glands cut every 3-4 mm. Location and volume estimation of cancer foci by PHS were undertaken using two methods; a manual method and an embedded software tool. In this report we evaluate data obtained from a planned open study phase. The second phase of the study is 'blinded', and currently in progress. RESULTS: 31 patients were eligible for this phase. Three patients were excluded from analysis due to inadequate scan acquisition and pathology violations of the standard operating procedure. One patient withdrew from the study after 3D TRUS examination. PHS detected cancer >= 0.20 mL in 25/27 prostates (sensitivity 93%). In all, 23 patients had an index focus >= 0.5 mL at pathology, of which 21 were identified as >= 0.5 mL by PHS using the manual method (sensitivity 91%) and 19 were correctly identified as >= 0.5 mL by the embedded tool (sensitivity 83%). In 27 patients, histological analysis found 32 cancerous foci >= 0.2 mL, located in 97 of 162 sextants. After sextant analysis, PHS showed a 90% sensitivity and 72% specificity for the localisation of lesions >= 0.2 mL within a sextant. CONCLUSIONS: PHS has the ability to identify and locate prostate cancer and consequently may aid in pre-treatment and pre-surgical planning. In men with a lesion identified, it has potential to enable improved targeting, allowing better risk stratification by obtaining more representative cores. However further verification from the results of the blinded phase of this study are awaited. PMID- 22093967 TI - The phylogeny of the BEP clade in grasses revisited: evidence from the whole genome sequences of chloroplasts. AB - Despite the considerable efforts to reconstruct the phylogeny of grasses, the relationships among the subfamilies Bambusoideae, Pooideae and Ehrhartoideae in the BEP clade remain unresolved. Here we completely sequenced three chloroplast genomes of representative species from Bambusoideae and Ehrhartoideae and obtained 19 additional chloroplast genome sequences of other grasses from GenBank. Using sequences of 76 chloroplast protein-coding genes from the 22 grass species, we fully resolved the phylogeny of the BEP clade. Our results strongly supported the (B,P)E hypothesis, i.e., Bambusoideae and Pooideae are more closely related than Ehrhartoideae. This result was not biased by systematic or sampling errors and was impervious to phylogenetic methods or model specification. The divergence time estimate suggests that the initial diversification of the BEP clade into three subfamilies happened within a short time period (~ 4 MY). The presence of these short internal branches may explain the inability of previous studies to achieve a confident resolution of the BEP clade. The combination of the sequences of the entire chloroplast genomes provided sufficient phylogenetic information to resolve the BEP phylogeny fully. These results provide a valuable evolutionary framework for comparative and functional genomic studies using the grass family as a model system. PMID- 22093968 TI - Performance evaluation of the Vitros anti-hepatitis C virus antibody assay for use in clinical laboratories. AB - OBJECTIVES: We evaluated the performance of Vitros anti-HCV assay. DESIGN AND METHODS: Precision performance was assessed for 20 days. A total of 1011 sera were tested for anti-HCV with Vitros and Elecsys assays. Specimens positive for any of the two assays were retested with Architect assay. Discrepant results were evaluated with recombinant immunoblot assay (RIBA) and HCV RNA quantification. RESULTS: Total imprecision of Vitros assay was 11.6% and 3.3% CV for negative and positive QC. Among the 1011 sera, 17 showed discrepant results between the three assays. Six were positive and three negative for RIBA. HCV RNA was not detected from all discrepant cases. Sensitivity and specificity were 99.5% and 99.5% for the Vitros, and 100.0% and 99.9% for the Elecsys assay. CONCLUSIONS: Sensitivities and specificities of the anti-HCV assays were sufficiently high for use in clinical laboratories, but retesting of weak positive results may be necessary. PMID- 22093969 TI - Betaine excretion correlates with plasma homocysteine when plasma lipids are elevated. AB - OBJECTIVES: To reconcile observing a positive correlation of betaine excretion with homocysteine in lipid disorder patients but not other study groups. DESIGN AND METHODS: Correlations were estimated in subgroups of a control group and the lipid disorder patients. RESULTS: Plasma non high-density lipoprotein (non-HDL) cholesterol differed (p<0.0001) between the groups. The correlation increased with the median plasma non-HDL cholesterol in subgroups. CONCLUSIONS: This correlation is associated with patients with elevated plasma lipids. PMID- 22093970 TI - Three-dimensional imaging of sulfides in silicate rocks at submicron resolution with multiphoton microscopy. AB - We report the first application of multiphoton microscopy (MPM) to generate three dimensional (3D) images of natural minerals (micron-sized sulfides) in thick (~120 MUm) rock sections. First, reflection mode (RM) using confocal laser scanning microscopy (CLSM), combined with differential interference contrast (DIC), was tested on polished sections. Second, two-photon fluorescence (TPF) and second harmonic signal (SHG) images were generated using a femtosecond-laser on the same rock section without impregnation by a fluorescent dye. CSLM results show that the silicate matrix is revealed with DIC and RM, while sulfides can be imaged in 3D at low resolution by RM. Sulfides yield strong autofluorescence from 392 to 715 nm with TPF, while SHG is only produced by the embedding medium. Simultaneous recording of TPF and SHG images enables efficient discrimination between different components of silicate rocks. Image stacks obtained with MPM enable complete reconstruction of the 3D structure of a rock slice and of sulfide morphology at submicron resolution, which has not been previously reported for 3D imaging of minerals. Our work suggests that MPM is a highly efficient tool for 3D studies of microstructures and morphologies of minerals in silicate rocks, which may find other applications in geosciences. PMID- 22093971 TI - [User satisfaction in the Virgen del Valle Geriatric Hospital, Toledo]. AB - OBJECTIVE: Knowing the degree of satisfaction of inpatients at a geriatric hospital METHODS: Observational and descriptive study. Period 23/12/2008 to 02/24/2009. Scope Geriatric Hospital (acute unit and middle stay unit). Discharged patient population. SERVQUAL adapted questionnaire. Main outcomes (received attention, environment, attitude and care professionals, overall satisfaction) analyzed using frequencies and percentages. Comparison of variables with chi square. Suggestions section grouped by category, expressed as frequencies. RESULTS: 159 respondents surveyed. in 50.90% times the family answered. Care received was valued as good and very good in 92%. Environment rating good or very good 75.6%. Professional attitude always nearly always 82.9%. 89.30% would recommend the hospital and overall satisfaction level of 52.20% very satisfied. Suggestions section was completed in 63 questionnaires, we found 20 gratitudes. Respondents that expressed overall satisfaction quite satisfied and very pleased noted to feel trust and security nearly always and always (p =0.0009). CONCLUSIONS: Overall satisfaction levels have been high. Most value good or very good to all professionals. Regarding attitude and care professionals most satisfied or very satisfied. We must improve infrastructure. PMID- 22093972 TI - Performance of sequencing batch biofilm reactors with different control systems in treating synthetic municipal wastewater. AB - This study aimed to evaluate the performances of sequencing batch biofilm reactors (SBBRs) in removing nitrogen and phosphorus from synthetic municipal wastewater with different carbon to total nitrogen (C/N) ratios. The effect of control systems, including an intelligent control system (ICS) and conventional timer control system (TCS) on the performance of SBBRs was also investigated. When C/N ratios were 10.0, 5.0 and 3.3, the average COD removal efficiencies in the ICS-SBBR reached 87.7%, 92.3% and 97.6%, while total phosphorous (TP) removals reached 95.0%, 97.0% and 97.2%. When the C/N ratio was 5.0, the TN removal efficiency was 81.0% under ICS and 65.4% under TCS. Moreover, compared with TCS-SBBR, both reaction time and aeration time were shortened by 180 min and 157 min, respectively, in the ICS-SBBR. Therefore, the ICS-SBBR has potential in practical applications for significant nitrogen and phosphorus removal and energy savings. PMID- 22093973 TI - Bioconversion of crude glycerol feedstocks into ethanol by Pachysolen tannophilus. AB - Glycerol, the by-product of biodiesel production, is considered as a waste by biodiesel producers. This study demonstrated the potential of utilising the glycerol surplus through conversion to ethanol by the yeast Pachysolen tannophilus (CBS4044). This study demonstrates a robust bioprocess which was not sensitive to the batch variability in crude glycerol dependent on raw materials used for biodiesel production. The oxygen transfer rate (OTR) was a key factor for ethanol production, with lower OTR having a positive effect on ethanol production. The highest ethanol production was 17.5 g/L on 5% (v/v) crude glycerol, corresponding to 56% of the theoretical yield. A staged batch process achieved 28.1g/L ethanol, the maximum achieved so far for conversion of glycerol to ethanol in a microbial bioprocess. The fermentation physiology has been investigated as a means to designing a competitive bioethanol production process, potentially improving economics and reducing waste from industrial biodiesel production. PMID- 22093974 TI - Pre-treatment optimization of Scenedesmus obliquus microalga for bioethanol production. AB - The present work deals with the optimization of cellular disruption and sugar extraction from the microalgae Scenedesmus obliquus (Sc) for bioethanol production. Among the physical and physicochemical methods tested, the best results were obtained with acid hydrolysis by H(2)SO(4) (2N), at 120 degrees C for 30 min and using dried biomass. The sugar extraction efficiency level reached was 95.6% when compared to the harsh quantitative acid hydrolysis. The influence of other parameters such as biomass loading and number of extraction cycles were also evaluated. The results obtained in the latter case showed that a unique hydrolysis step is sufficient. PMID- 22093975 TI - Relationship of cell-wall bound fatty acids and the demulsification efficiency of demulsifying bacteria Alcaligenes sp. S-XJ-1 cultured with vegetable oils. AB - Considering that the surface properties of demulsifying cells correlate with their demulsification efficiency, the demulsifying bacteria Alcaligenes sp. S-XJ 1 with various surface properties were obtained using different vegetable oils as carbon sources. The results show that better performance was achieved with demulsifying bacteria S-XJ-1 possessing a relatively high cell surface hydrophobicity (CSH) and total unsaturated degree for the cell-wall bound fatty acids. There also appeared to be a correlation between the specific cell-wall bound fatty acid components of the bacteria, in terms of carbon chain length or degree of unsaturation, and either CSH or demulsification efficiency. The fatty acids attached to the cell wall were mainly composed of palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2) and linolenic acid (C18:3). C18:1 and C18:2 had a positive effect on the formation of CSH, while C18:0 and C18:3 had the opposite effect. PMID- 22093976 TI - Pretreatment of paddy straw with Trametes hirsuta for improved enzymatic saccharification. AB - Delignification of paddy straw with the white-rot fungus, Trametes hirsuta under solid state fermentation, for enhanced sugar recovery by enzymatic saccharification was studied. T. hirsuta MTCC136 showed high ligninase and low cellulase activities. Solid state fermentation of paddy straw with T. hirsuta enhanced carbohydrate content by 11.1% within 10 days of incubation. Alkali extracts of Trametes pretreated paddy straw showed high absorbance at 205 nm indicating high lignin break down. The amount of value-added lignin recovered from the Trametes pretreated paddy straw was much higher than controls. Enzymatic hydrolysis of the Trametes pretreated paddy straw yielded much higher sugars than controls and yields increased till 120 h of incubation. Saccharification efficiency of the biologically pretreated paddy straw with Accelerase(r)1500 was 52.69% within 72 h and was higher than controls. Thus, the study brings out the delignification potential of T. hirsuta for pretreatment of lignocellulosic substrate and facilitating efficient enzymatic digestibility of cellulose. PMID- 22093977 TI - Efficient production of D-(-)-lactic acid from broken rice by Lactobacillus delbrueckii using Ca(OH)2 as a neutralizing agent. AB - Effects of Ca(OH)(2), NH(4)OH, and NaOH as neutralizing agents for efficient recovery of lactic acid was investigated. Lactic acid was produced from broken rice in a simultaneous saccharification and fermentation (SSF) process with Lactobacillus delbrueckii. Consumption of glucose (from broken rice) by the cells and the cell growth were the best with Ca(OH)(2) among the three neutralizing agents used. Maximum productivities of lactic acid reached with Ca(OH)(2), NH(4)OH, and NaOH were 3.59 g l(-1) h(-1), 1.51 g 1(-1) h(-1), and 1.40 g l(-1) h(-1), respectively. Ca(OH)(2) reduced the lactate molarity of the fermentation broth, and thus resulted in the highest lactic acid productivity. Furthermore, it was apparently clear that divalent cation (Ca(2+)) was more effective in neutralizing the cultures compared to monovalent (Na(+) and NH(3)(+)) cations. PMID- 22093978 TI - Enzymatic routes for the production of mono- and di-glucosylated derivatives of hydroxytyrosol. AB - In this work, a new eco-friendly procedure for the synthesis of hydroxytyrosol and tyrosol alpha-glycosidic derivatives was proposed by using the marine alpha glucosidase from Aplysia fasciata, and a commercial tyrosinase from mushroom for the bioconversion of tyrosol glycosidic derivatives into the corresponding hydroxytyrosol products. New hydroxytyrosol mono- and di-saccharide derivatives were synthesized at final concentrations of 9.35 and 10.8 g/l of reaction, respectively, and their antioxidant activity was evaluated by DPPH test. The best antioxidant agent resulted the (3,4-dihydroxyphenyl) ethyl-alpha-D glucopyranoside; it showed a radical scavenging activity similar to that of the hydroxytyrosol, together with an increased hydrosolubility. This molecule could be a good response to many food industry demands, always in search of cheap antioxidants with nutritional properties to improve the nutritional value and the quality of foods. PMID- 22093980 TI - [High altitude medicine in China: present aspects, progress and prospect]. PMID- 22093979 TI - Phenol degradation activity and reusability of Corynebacterium glutamicum coated with NH(2)-functionalized silica-encapsulated Fe3O4 nanoparticles. AB - In this study, a novel method to immobilize and separate Corynebacterium glutamicum for phenol degradation was developed using Fe(3)O(4) nanoparticles (NPs). The Fe(3)O(4) NPs were encapsulated with silica and functionalized with NH(2) groups to enhance their capacity to adsorb on the cell surface. The results showed that the NH(2)-functionalized silica-encapsulated Fe(3)O(4) NPs strongly adsorbed on the cell surface of C. glutamicum during 32 d culture without any interruptions of their normal cell growth. The coated C. glutamicum were easily separated from the culture broth within 2 min by applying an external magnetic field Also, the coated C.glutamicum were able to completely degrade 50 ppm phenol in the culture broth after 8d culture at 30 degrees C. Concerning reusability, the coated cells could completely degrade phenol during the first 2 cycles, and retain ~60% activity of phenol degradation for the third and four cycles. PMID- 22093981 TI - [Association of single nucleotide polymorphism in human CYP8B1 gene with gallstone disease]. AB - OBJECTIVE: To identify the single nucleotide polymorphisms of human CYP8B1gene and explore the association of some of these SNPs with gallstone disease in Chinese population. METHODS: The exon and part of promoter were sequenced by a fluorescent labeling automatic method to identify and characterize the SNPs in Chinese population. For SNPs with an allelic frequency of over 10%, a case control study was performed in patients and controls. RESULTS: Eleven SNPs were found within a 5119 bp region. Among them, 1 was in coding region, 5 in promoter and 5 in 3'-UTR. There were 3 novel SNPs and 12 SNPs in SNP database were not found. The allelic frequency of rs3732860 polymorphism showed a significant difference (P = 0.022) in the association study. The subjects with A allele had a significantly lower frequency of gallstone disease than those with G allele (OR = 1.465, 95%CI 1.055 - 2.034, P = 0.023). CONCLUSION: SNP rs3732860 of CYP8B1 gene is associated with gallstone disease in Chinese population. And A allele may play a protective role in the pathogenesis of gallstone. PMID- 22093982 TI - [Tone recognition of REZ-1 multi-channel unilateral cochlear implants for profoundly postlingual deaf adults]. AB - OBJECTIVE: To assess the tone recognition of cochlear-implant subjects by a REZ-1 device. METHODS: Speech recognition experiments were conducted to measure the tone recognition with standard assessment table and standard testing program. A total of 34 postlingual hearing-impaired adults who were native speakers of Mandarin undergoing operations from June to October, 2009 were tested and scored both preoperatively and postoperatively (1, 2, 3, 6, 12 months post-implantation) for speech recognition. RESULTS: All patient scores of speech recognition (initials, finals, monosyllabic words & tones) decreased gradually during the postoperative follow-up period. Preoperative speech recognition scores were all 0. And after a 12-month training, their average scores were increased significantly [(70 +/- 8)% +/- (82 +/- 8)%]. Significant statistical differences existed between pre- and post-implantation in each test (P < 0.01). CONCLUSION: REZ-1 cochlear implantation may improve the tone recognition of adults with severe-to-profound postlingual hearing loss in a quiet environment. PMID- 22093983 TI - [Anatomic variations and corresponding surgical techniques of total anomalous pulmonary venous connection]. AB - OBJECTIVE: To describe the anatomic variations of total anomalous pulmonary venous connection (TAPVC) and its corresponding surgical techniques. METHODS: A total of 143 TAPVC subjects were hospitalized from April 1981 to July 2010. Those patients with other complex congenital heart diseases, such as transposition of great artery and single ventricle, were excluded. A pathological diagnosis was made by echocardiography, magnetic resonance imaging, computed tomography, catheterization and intra-operative findings. The specific types of TAPVC were as follows:supra-cardiac (49.7%, 71/143), cardiac (40.6%, 58/143), infra-cardiac (4.2%, 6/143) and mixed (5.6%, 8/143). The subtypes were classified by the pathway of common confluence, distribution of pulmonary vein and their orifice site. The techniques of surgical repairs included modified Warden procedure and pulmonary vein transplantation. RESULTS: The patients with supra-cardiac type were further divided into 4 subtypes according to the course of vertical veins and their orifice site: right and left veins forming a common confluence, then draining into vertical and innominate veins (n = 65); common confluence of pulmonary vein drainage into superior vena cava through a short vertical vein at the right pulmonary hilus (n = 3); right and left pulmonary veins separately draining into superior vena cava (n = 2); common confluence draining into innominate vein through a right path beside trachea (n = 1). Cardiac types were further divided into 3 subtypes: coronary sinus (n = 20), right atrium (n = 37) and right atrium & sinus (n = 1). Infra-cardiac type had no subtype. Mixed type was more complex and it was further divided into 3 subtypes: bilateral & symmetrical connection (right 2 + left 2, n = 5); bilateral & asymmetrical connection (3 + 1, n = 3). Surgical repairs were performed on 135 patients. The surgical mortality of TAPVC was 5.9% (8/135). And there was no late death. The major causes of death were pulmonary infection and low cardiac output syndrome. CONCLUSION: A detailed classification of TAPVC is of great importance for surgical approaches and methodological designs. And an individualized surgical plan yields excellent patient outcomes. PMID- 22093984 TI - [Effects of ventricular demand and dual-chamber pacing models on the long-term clinical outcome and cardiac remodeling in patients with symptomatic bradycardia]. AB - OBJECTIVE: To assess the effects of VVI (ventricular demand) and DDD (dual chamber) pacing models on cardiac remodeling and the long-term clinical outcome of patients with symptomatic bradycardia. METHODS: All patients with DDD and VVI pacing models at our hospital from January 1991 to January 2003 were retrospectively analyzed. RESULTS: After a follow-up period of over 8 years in DDD and VVI groups (97 +/- 27, 107 +/- 44 months), left atrial diameter [(45 +/- 12) mm vs (39 +/- 12) mm, P < 0.01] and left ventricular end-diastolic diameter [(53 +/- 11) mm vs (50 +/- 9) mm, P = 0.01] in 57 patients with VVI pacing model were markedly enlarged than those at pre-implantation. And tricuspid regurgitation increased (42.4% vs 16.9%, P < 0.05). But in 59 patients with DDD pacing model, except for increased tricuspid regurgitation (42.1% vs 10.5%, P < 0.01), left atrial diameter [(37 +/- 5) mm vs. (35 +/- 5) mm, P = 0.07] and left ventricular end-diastolic diameter [(47 +/- 7) mm vs (47 +/- 5) mm, P = 0.32] were not significantly different. Mitral regurgitation significantly increased only in the VVI group (P < 0.01). The increases of left ventricular end-diastolic diameter (P = 0.04), mitral valve (P = 0.02) and tricuspid regurgitation (P < 0.01) were much more pronounced in the VVI group than those in the DDD group. Left ventricular ejection fraction (LVEF) showed no difference with that at pre implantation (P = 0.11 in DDD group, P = 0.05 in VVI group). But the LVEF value was lower (P = 0.04) while the incidence of thrombosis was higher (P = 0.03) in the VVI group than those in the DDD group at post-implantation. However, the incidence of atrial fibrillation (P = 0.14), hospitalization (P = 0.08) and survival (P = 0.77) showed no significant difference between two groups. CONCLUSION: DDD pacing offers more benefits over VVI pacing through improving cardiac functions and arresting left ventricular remodeling. However, neither groups showed any difference in decreasing mortality rate and hospitalization. Moreover, both pacing modes fail to reverse cardiac electrical and anatomical remodeling. It is imperative to explore more physiological pacing site and rational atrioventricular (AV) interval to improve the prognosis of patients. PMID- 22093985 TI - [Association of visceral adiposity with urinary albumin excretion in type 2 diabetics]. AB - OBJECTIVE: To decipher the association of visceral adiposity (VA) with 24-hour urinary albumin excretion (24 h-UAE) in type 2 diabetics. METHODS: We collected the clinical data, VA, subcutaneous adiposity (SA), 24 h-UAE, blood lipids, fasting blood glucose, glycosylated hemoglobin, insulin and tumor necrosis factor (TNF)-alpha of type 2 diabetic inpatients at our hospital. According to the quartile of VA, the subjects were divided into 4 groups. And their profiles were compared with regards to the level of 24 h-UAE and the incidence of heavy proteinuria. And their relative intensities and the linear relationship of VA and lg (24 h-UAE) were analyzed. RESULTS: lg (24 h-UAE) of groups C and D was larger than that of groups A and B. With the rising level of VA, the prevalence of heavy proteinuria increased. A moderate correlation existed between VA and lg (24 h UAE) (r = 0.51). lg (24 h-UAE) increased 0.26 units as VA expanded 100 cm(2), i.e. 0.15 units after relative factor adjusting. After gender and triglyceride adjusting, the odds ratio of heavy albuminuria in group C was 2.75 versus that in group A. And the OR was 3.87 in group D. CONCLUSION: Expansion of VA is a risk factor for an elevated risk of 24 h-UAE. With the expansion of VA, the prevalence of heavy albuminuria increases. PMID- 22093986 TI - [Diagnostic values of self-assessment tool for Asians for osteoporosis in aged men]. AB - OBJECTIVE: To evaluate the diagnostic values of osteoporosis self-assessment tool for Asians (OSTA) in aged men. METHODS: Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) in 382 male outpatients. Their data were collected. After excluding such influencing factors of BMD as diseases or drugs, they were divided into 3 groups according to the WHO osteoporosis diagnosis value or age. The correlation between OSTA index and BMD was analyzed by Spearman correlation. The concordance of OSTA and BMD were calculated and analyzed by a four-fold table. RESULTS: The prevalence of osteoporosis was 9.42% and osteopenia 42.67%. Age increased gradually in the osteoporosis, osteopenia and normal bone mass groups. But OSTA index, BMD (including lumbar vertebrae L(1 4), femoral neck, trochanter and hip) and weight decreased gradually in those groups. The percent of normal bone mass decreased with advancing age. And the percentages were 60.68%, 51.97% and 33.33% respectively. Osteoporosis increased in the older group (> 80 years old) and the percentage was 24.64% accounting for 94.44% of all osteoporotic subjects. Judging by the OSTA index, the rate of low osteoporotic risk decreased with advancing age. But the rates of mid-risk and high-risk increased. The correlation coefficients of OSTA index and BMD in femoral neck, trochanter, hip and L(1-4) was 0.33, 0.28, 0.29 and 0.06 respectively. And the correlation between OSTA index and BMD had statistical significance except for L(1-4). The sensitivity, specificity, coincidence and Youden index of OSTA index with a T score cutoff of -1 of BMD were 56.28%, 64.48%, 60.21% and 0.21 respectively versus 86.11%, 57.80%, 60.47% and 0.44 with a T score cutoff of -2.5. CONCLUSION: Correlation exists between OSTA index and BMD. The sensitivity, specificity and coincidence of OSTA index are excellent based upon the standard of BMD by DXA. It is a useful and simple diagnostic tool of osteoporosis. PMID- 22093987 TI - [Impact of response of positive axillary nodes to neoadjuvant chemotherapy on breast cancer survival]. AB - OBJECTIVE: To compare the distant disease-free survival between breast cancer patients with nodal pathological complete response (pCR) and those with nodal residual disease (RD) after neoadjuvant chemotherapy. METHODS: The clinical and pathological data of 376 needle biopsy proved node positive breast cancer patients undergoing neoadjuvant chemotherapy were retrospectively analyzed. RESULTS: The median follow-up time was 24 months (range: 5 - 100). The pCR rate of axillary lymph node was 30.9%. And the three-year distant disease-free survival (DDFS) rates were 91.7% and 78.8% in the patients with axillary lymph node pCR and RD respectively. According to the Log-rank test, there were significant differences in survival curves (P = 0.016). Multivariate analysis showed that the relative risk of DDFS for patients with RD was 2.14 folds of than that of the pCR group (P = 0.047). No significant difference existed between the disease-free survival (DFS) curve in two groups. DDFS had significant differences between the patients with the number of lymph node metastasis <= 3 and >= 4 in the RD group (P = 0.001). CONCLUSION: The distant disease-free survival of node positive breast cancer is associated with the status of axillary lymph node after neoadjuvant chemotherapy. PMID- 22093988 TI - [Serum alpha1-acid glycoprotein, imatinib concentration and efficacy in chronic myeloid leukemia patients]. AB - OBJECTIVE: To explore the relationship between serum alpha1-acid glycoprotein (AGP), disease progression, imatinib plasma trough concentration and efficacy in the patients with chronic myeloid leukemia (CML). METHODS: A total of 112 CML patients were recruited from August 2008 to February 2010 in our hospital. There were 72 males and 40 females with a median age of 39 years old (range: 6 - 76 years old). Among them, 102 patients were in chronic phase, 4 in accelerated phase and 6 in blastic phase. Ninety-nine patients were treated with imatinib while 13 patients received hydroxyurea. Twenty healthy blood donors were designated as the control group. The serum AGP levels of all patients were detected by immuno-turbidimetric assay. And the concentrations of AGP and imatinib were detected in 12 patients before and after 3 months of imatinib therapy respectively. For 84 CML patients, their plasma trough concentrations of imatinib were detected by high performance liquid chromatography-tandem mass spectrometry simultaneously. All patients were divided into 5 groups by efficacy to evaluate the significance of serum AGP and its relationship with imatinib concentration. RESULTS: Serum AGP of no response (NR) group [(1.18 +/- 0.26) g/L] was significant higher than that of complete cytogenetic response (CCR), complete hematologic response (CHR) and control group [(0.60 +/- 0.21), (0.71 +/- 0.17), (0.52 +/- 0.15) g/L, all P < 0.05]. Serum AGP of accelerated/blastic phase group [(1.28 +/- 0.50) g/L] was significant higher than CCR or control group (P < 0.05). Serum AGP of CHR group was higher than that of control group (P < 0.05). No significant difference existed between CCR, CHR or control group (P > 0.05). There were no significant differences between NR, relapse or accelerated/blastic phase group (P > 0.05). The serum AGP of 12 patients on a 3-month therapy of imatinib were lower than that of patients at pre-treatment [(0.54 +/- 0.17) g/L vs (0.83 +/- 0.31) g/L, P < 0.01]. The plasma trough concentration of imatinib was (1307 +/- 586) ug/L (range: 109 - 3400 ug/L) in 84 patients. And it was positively correlated with the serum level of AGP (r = 0.443, P < 0.01). CONCLUSION: The serum level of AGP can reflect the in vivo loads of leukemic cells for CML patients. There is a positive correlation between the serum level of AGP and the plasma trough concentration of imatinib. Serum AGP can be used as a monitoring index of efficacy for CML patients. PMID- 22093989 TI - [Effects of Foxp3 knockdown on the functions of human regulatory T cells]. AB - OBJECTIVE: To employ the technology of interfering RNA (RNAi) to identify the role of Foxp3 in the in vitro suppressive effect of human regulatory T cell (Treg) on effector T cells. METHODS: Expanded human Treg were transfected with siRNA targeting Foxp3 genes. The transfection efficiency, the level of corresponding gene and its protein expression were measured by fluorescent microscopy, fluorescence-activated cell sorting (FACS), real-time PCR and Western blot respectively. The phenotypes of Treg were analyzed by FACS. The siRNA transfected Treg was then co-cultured with porcine PBMC or human PBMC-stimulated autologous CD4+CD25- T cells. Their proliferations were examined by WST-1. Treg and autologous CD4+CD25- T cell-related suppressive cytokines were assessed by ELISA. RESULTS: A 68% transfection efficiency in expanded Treg was achieved for Foxp3 siRNA. Real-time PCR revealed a 61.4% mRNA knockdown induced by siRNA targeting Foxp3 genes in Treg versus the control (P < 0.01). Some Treg-associated surface markers were significantly altered versus the control. And the production of suppressive cytokines was lowered. These changes were correlated with the diminished Treg activity in suppressing the proliferation of effector CD4+CD25- T cells. There was 83% suppression by non-transfected Treg vs 48% suppression by Foxp3 siRNA transfected Treg in xeno-immune response (P < 0.05); and 65% suppression by non-transfected Treg vs 48% suppression by Foxp3 siRNA transfected Treg in allo-immune response (P < 0.01). CONCLUSION: Foxp3 is a key intracellular marker for maintaining the phenotypes and functions of Treg. PMID- 22093990 TI - [STAT5 phosphorylation levels of erythropoietin and thrombopoietin receptors in CD34(+)CD59(-) and CD34(+)CD59(+) bone marrow cells of patients with paroxysmal nocturnal hemoglobinuria]. AB - OBJECTIVE: To study the STAT5 phosphorylation levels of erythropoietin receptor (EPOR) and thrombopoietin receptor (TPOR) in CD34(+)CD59(-) and CD34(+)CD59(+) bone marrow cells of the patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: The bone marrow mononuclear cells (BMMNC) were extracted from 23 PNH patients treated at our department from April 2010 to February 2011 and 11 normal controls. The mean fluorescence intensity (MFI) of phosphorylated STAT5 (P-STAT5) in CD34(+)CD59(+) cells and CD34(+)CD59(-) cells with or without the stimulation of 10 U/ml EPO and 50 U/ml TPO were examined by flow cytometry. RESULTS: (1) Without stimulation, the P-STAT5 MFI in CD34(+)CD59(-) cells of PNH patients was significantly lower than that of CD34(+)CD59(+) cells (31 +/- 15 vs 74 +/- 47, P < 0.01). And it was 59 +/- 23 in normal control CD34(+)CD59(+) cells (P < 0.05). No statistic difference existed between the CD34(+)CD59(+) cells of PNH patients and the normal control CD34(+)CD59(+) cells. (2) Under the stimulations of EPO and TPO, the P-STAT5 MFI was significantly lower in CD34(+)CD59(-) cells of PNH patients than that of CD34(+)CD59(+) cells (49 +/- 24 and 51 +/- 41 vs 120 +/- 82 and 124 +/- 87, both P < 0.01). For the normal control CD34(+)CD59(+) cells, they were 79 +/- 47 and 98 +/- 53 respectively (P < 0.05). No statistic difference existed between the CD34(+)CD59(+) cells of PNH patients and the normal control CD34(+)CD59(+) cells. P-STAT5 MFI was elevated after the stimulations of EPO and TPO. The increments of CD34(+)CD59(+) cells in PNH patients were significantly higher than those of CD34(+)CD59(-) cells (49 +/- 11 and 54 +/- 43 vs 17 +/- 4 and 16 +/- 6, both P < 0.01). CONCLUSION: Under the in vitro stimulations of EPO and TPO, the STAT5 phosphorylation levels of EPO and TPO receptors in normally cloned hematopoietic stem cells in PNH patients are obviously superior to those in abnormally cloned counterparts. PMID- 22093991 TI - [Oral controlled-release oxycodone for uterine cramping pain after cesarean section]. AB - OBJECTIVE: To evaluate whether combined oral oxycodone hydrochloride controlled release tablets plus paracetamol and tramadol hydrochloride tablets is better than epidural analgesia with respect to uterine cramping pain control and side effects after cesarean section. METHODS: Sixty consecutive patients scheduled for cesarean section from April to May, 2010 were randomized to either patient controlled epidural analgesia with 0.1% ropivacaine, 0.1 ug/ml sufentanil (for postoperative 48 h) plus injected pethidine on demand (EDA group) or controlled release oxycodone (2 * 15 mg for 1st postoperative 24 h; 2 * 10 mg for 2nd postoperative 24 h), paracetamol & tramadol hydrochloride tablets (8 * 1 tablet for postoperative 48 h) orally plus pethidine injection on demand (OXY group). Two groups were compared with respects to uterine cramping pain control when the oxytocin infusion (20 U plus 500 ml 5% glucose solution, iv. gtt within 2 h) once per day for postoperative 3 days as determined by the means of a visual analogue scale (VAS), pethidine consumption, side effects and costs. RESULTS: The EDA group experienced significant more pain than the OXY group when the oxytocin infusion was administered (mm) [50.0 (15.0, 72.5) vs 25.0 (0, 40.0), 60.0 (47.5, 72.5) vs 20.0 (0, 30.0), 35.0 (20.0, 50.0) vs 0 (0, 20.0)]. all P < 0.05). Pethidine was used for pain control in 2 patients (150 mg total) of EDA group during the oxytocin infusion whereas none of the OXY group received an injection of pethidine. There was a higher level of maternal satisfaction with a lower analgesic dose in the EDA group (80.9 +/- 9.3 vs 90.0 +/- 9.8, P < 0.01). The median duration of hospital stay was around 5 days in both groups. CONCLUSION: Postoperative pain control after cesarean section with the above combined regimen is superior to EDA in terms of a lower cost and a higher level of maternal satisfaction. PMID- 22093992 TI - [Effects of endothelial progenitor cells on spermatogenic functions in testicular detorsion in rats]. AB - OBJECTIVE: To investigate the effects of transplanted endothelial progenitor cells (EPCs) on the spermatogenic functions in testicular detorsion. METHODS: Bone-marrow-derived EPCs were obtained from rats and transfected by enhanced green fluorescent protein adenovirus (Ad-eGFP). The rats were divided into 3 groups (n = 6 each). In the sham group, left testis was not twisted. In the ischemia reperfusion injury (IRI) group, 1 ml saline was injected into the femoral vein of each rat after testicular detorsion. In the EPCs group, 1 ml EPCs suspension (1.0 * 10(6) EPCs) was injected into each rat after testicular detorsion. The Ad-eGFP transfected EPCs were injected into the 3 additional rats of testicular torsion-detorsion. At Day 5 post-transplantation, the characteristics of transplanted EPCs homing were detected. And the pathological changes and apoptotic cells/seminiferous tubules in left testis were examined. RESULTS: When the value of multiplication of infection (MOI) was at 50, the transfection rate of EPCs by Ad-eGFP exceeded 73.7%. At Day 5 post-treatment, the cells exhibiting green fluorescence were detected in left testis. The germ cells in rats of the sham group were normal. And the ratio of apoptotic cells to seminiferous tubules was 0.09 +/- 0.02. The germ cells in rats of the IRI group were much fewer. And the ratio of apoptotic cells to seminiferous tubules was 2.82 +/- 0.81. As compared with the IRI group, seminiferous epithelium was thicker in the EPCs group. And the ratio of apoptotic cells to seminiferous tubules was 0.32 +/- 0.09 in the EPCs group. It was much smaller than that in the IRI group. There was significant difference (P < 0.01). CONCLUSION: The transplantation of EPCs is effective for treating the spermatogenic dysfunctions caused by testicular torsion so as to greatly enhance the spermatogenic functions. PMID- 22093993 TI - [Effects of Akt2-siRNA on chemotherapeutic sensitivity and drug resistance in human lung cancer cells]. AB - OBJECTIVE: To explore the effects of oncogene protein v-akt-siRNA on the sensitivity of human lung cancer cell line NCI-H446 to cisplatin and drug resistance proteins in human lung cancer cells. METHODS: The small interfering siRNA expression vector targeting Akt2 gene (siAkt2) was constructed. And the NCI H446 cells were transfected with negative control vector or siRNA vector. The expressions of Akt2-mRNA and lung resistance-related protein (LRP) and P glycoprotein (P-gp) were detected by reverse transcription-polymerase chain reaction and immunocytochemistry respectively. NCI-H446 and transfected cells were treated by cisplatin for 24 h. The cell proliferation was measured by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay and cell apoptotic rate detected by flow cytometry. RESULTS: Akt2-mRNA decreased significantly in the transfected NCI-H446 cells versus the non-transfection group. And the expressions of LRP and P-gp proteins decreased significantly in the transfection group versus the control group (P < 0.01). The cell proliferation rate decreased from (60.2 +/- 2.8)% to (34.7 +/- 2.6)% (P < 0.01). The cell apoptotic rate increased from (19.3 +/- 1.6)% to (38.8 +/- 1.2)% after a therapy of cisplatin (P < 0.01). CONCLUSION: The siRNA targeting Akt2 can decrease the Akt2 expression, increase the chemotherapeutic sensitivity to cisplatin and partially reverse the cisplatin resistance of NCI-H446. The mechanism may be through the lowered expressions of LRP and P-gp. PMID- 22093994 TI - [Protection of hyperoxia-induced lung injury by granulocyte-macrophage colony stimulating factor via RAGE-NF-kappaB signaling pathway in newborn rats]. AB - OBJECTIVE: To explore the effects of granulocyte-macrophage colony-stimulating factor (GMCSF) on hyperoxia exposure lung injury in newborn rats and elucidate its protective mechanism of operating via the signaling pathway of advanced glycation end products (RAGE)-NF-kappaB. METHODS: Twenty-four 3-day-old SD rats from 3 litters were randomly divided into 3 groups. They were hyperoxia exposure plus GMCSF group (group A), hyperoxia exposure group (group B) and air exposure group (group C). The rats from groups A and B were placed in a sealed Plexiglas chamber with a minimal in-and-outflow, providing 6 - 7 exchanges per hour of chamber volume and maintaining O(2) levels above 95%. While the rats in group C only were exposed to air simultaneously. The rats in group A received subcutaneous injections of recombinant murine GMCSF (9 ug/kg) during hyperoxia exposure at 24 h, 72 h and 120 h respectively. And the rats in groups B and C received subcutaneous injections of saline vehicle alone at the same time point. Seven days later, all were sacrificed and immunohistochemistry was employed to assess the expression of RAGE in lung tissue. The levels of tumor necrosis factor alpha in bronchoalveolar lavage fluid (BALF) and serum samples were detected by ELISA (enzyme-linked immunosorbent assay). The RAGE mRNA and NF-kappaB mRNA in tissue homogenates were detected by RT-PCR while RAGE and NF-kappaB by Western blot. Also the values of lung damage score were calculated with microscopic histology. RESULTS: The value of lung damage score in group C, B and A was 0.46 +/- 0.20, 3.06 +/- 0.33 and 2.31 +/- 0.56 respectively, there was significantly difference among three groups (P = 0.000). The expression of RAGE mRNA and protein in three groups were 0.14 +/- 0.02, 0.34 +/- 0.06, 0.28 +/- 0.04 and 0.30 +/- 0.04, 0.76 +/- 0.11, 0.55 +/- 0.08 respectively. There were both significantly differences among three groups (P = 0.000, P = 0.000). The expression of NF-kappaB mRNA and protein in three groups were 0.41 +/- 0.21, 0.90 +/- 0.36, 0.69 +/- 0.30 and 0.41 +/- 0.26, 0.96 +/- 0.43, 0.77 +/- 0.33 respectively, there were both significantly difference among three groups (P = 0.000, P = 0.017). The level of TNF-alpha in BALF was 76 +/- 10, 224 +/- 42 and 143 +/- 24 respectively, there was significantly difference among three groups (P = 0.000). All indicators above in group B and group A were significantly more than those in group C (all P < 0.05), while these indicators in group A were lower than those in group B. But there was no difference in the level of TNF alpha of serum among three groups (P > 0.05). CONCLUSION: GMCSF may protect hyperoxia-induced lung injury via down-regulating the signaling pathway of RAGE NF-kappaB. PMID- 22093995 TI - [Differentiation of polygene-modified bone marrow mesenchymal stem cells into insulin-producing cells]. AB - OBJECTIVE: To evaluate the effects of insulin gene transcription regulators PDX 1, NeuroD1 and MafA on the differentiation of bone marrow mesenchymal stem cells (mMSCs) into insulin-producing cells. METHODS: Murine mMSCs were isolated, cultured and expanded. The base sequences of transcription factors PDX-1, NeuroD1 and MafA were obtained by total gene synthesis and the recombinant adenovirus vectors harboring target genes constructed and transfected into packaging cell line 293A. mMSCs were infected with adenovirus separately or together, and then differentiated in vitro into insulin-producing cells. Reverse transcription polymerase chain reaction (RT-PCR) was utilized to detect insulin gene expression, immunofluorescence for identifying the presence of insulin protein and insulin enzyme-linked immunosorbent assay (ELISA) for evaluating the secretory volume of insulin. RESULTS: The differentiation extent of mMSCs into beta-cell was analyzed. The beta-cell-specific transcriptional regulators and insulin gene were expressed in mMSCs after transfection. Immunofluorescent analyses revealed the activated expression of insulin in the cytoplasm of differentiated cells. A significant content of insulin was released in these cells in response to a certain concentrations of glucose stimulation. The insulin content of mMSCs infected with a combination of three transcription factors was significantly higher than that of the control group [(112.84 +/- 9.67) mU/L vs (1.60 +/- 0.22) mU/L, P < 0.05]. CONCLUSION: After modification by transcriptional factors PDX-1, NeuroD1 and MafA, mMSCs can secrete insulin through starting endogenous insulin gene transcription. PMID- 22093996 TI - Analysis and clinical correlation of genetic variation in cytomegalovirus. AB - BACKGROUND: Cytomegalovirus (CMV) displays genetic polymorphisms in multiple genes, which may result in important virulence differences. Glycoprotein N (gN) and immediate early 1 (IE1) are key viral genes and immune targets. We aimed to characterize the molecular epidemiology of gN and IE1 genotypes in organ transplant patients with CMV disease in the context of clinical and virologic endpoints. METHODS: A total of 240 patients with CMV disease had genotyping analysis by nested polymerase chain reaction assays and sequencing using blood samples obtained at disease onset. Results were correlated with viral clearance kinetics and recurrence. RESULTS: Complex patterns of gN and IE1 genotypes were present with no clear genetic linkages. No single genotype of IE1 or gN was associated with poorer outcome. For example, different gN or IE1 genotypes had comparable baseline viral load, clearance half-lives, time to clearance, and rates of virologic recurrence. Mixed infection was present at IE1 in 15.8% and gN in 21.9%, but analysis of a single gene was insufficient to detect all mixed infections. Infections caused by multiple strains, as opposed to single strains, were associated with higher baseline viral loads (P = 0.011), delayed viral clearance (P = 0.033), and higher rates of virologic recurrence (P = 0.008). CONCLUSIONS: Genetic diversity in CMV is complex. Specific gN or IE subtypes do not seem to affect in vivo viral virulence patterns in single-strain infections. Mixed infections demonstrate associations with virologic outcomes that single strain infections do not. PMID- 22093997 TI - Enhancement of antimicrobial activities of whole and sub-fractionated white tea by addition of copper (II) sulphate and vitamin C against Staphylococcus aureus; a mechanistic approach. AB - BACKGROUND: Enhancement of antimicrobial plant products e.g. pomegranate extract by copper (II) sulphate is known. Such combinations have applications in various settings, including the identification of novel compositions to study, treat and control infection. METHODS: A combination of white tea (WT) (made allowing 10 minutes infusion time at 100 degrees C) was combined with 4.8 mM copper (II) sulphate and tested for antimicrobial effect on the viability of Staphylococcus aureus NCTC 06571. Comparisons were made with green (GT) and black (BT) teas. A WT sub-fraction (WTF < 1000 Da) was tested with copper (II) sulphate and 4.8 mM vitamin C. pH measurements of samples were taken for controls and to observe any changes due to tea/agent interaction. Catalase was used to investigate hydrogen peroxide release. UV-vis. was used to compare WT and WTF. RESULTS: A 30 minute incubation at room temperature of copper (II) sulphate alone and combined with WT reduced the viability of S. aureus NCTC 06571 by c.a 1 log10 cfu mL-1. GT and BT with copper (II) sulphate negated activity to buffer values. Combined with copper (II) sulphate, vitamin C, WTF and, vitamin C plus WTF all reduced the viability of S. aureus NCTC 06571 by c.a. 3.5 log10 cfu mL-1. Independent experiments showed the results were not due to pH effects. Adding WT or WTF to copper (II) sulphate resulted in increased acidity. Copper (II) sulphate alone and combined with WT required c.a 300 MUg mL-1 (final concentration) catalase to restore S. aureus viability, WTF with copper (II) sulphate and added vitamin C required c.a 600 MUg mL-1. WT and WTF UV-visible spectra were similar. CONCLUSIONS: WT showed no efficacy in the combinations tested. WTF was enhanced with copper (II) sulphate and further with vitamin C. WT and WTF increased acidity of copper (II) sulphate possibly via the formation of chemical complexes. The difference in WT/WTF absorbance possibly represented substances less concentrated or absent in WTF. Investigations to establish which WTF component/s and in what proportions additives are most effective against target organisms are warranted. PMID- 22093998 TI - Natural biopolymer for preservation of microorganisms during sampling and storage. AB - Stability of microbial cultures during sampling and storage is a vital issue in various fields of medicine, biotechnology, food science, and forensics. We have developed a unique bacterial preservation process involving a non-toxic, water soluble acacia gum polymer that eliminates the need for refrigerated storage of samples. The main goal of this study is to characterize the efficacy of acacia gum polymer for preservation of pathogenic bacteria (Bacillus anthracis and methicillin-resistant Staphylococcus aureus-MRSA) on different materials, used for swabbing and filtration: cotton, wool, polyester, rayon, charcoal cloth, and Whatman paper. Acacia gum polymer used for preservation of two pathogens has been shown to significantly protect bacteria during dehydration and storage in all tested samples at the range of temperatures (5-45 degrees C for MRSA and 40-90 degrees C for B. anthracis). Our results showed higher recovery as well as higher viability during the storage of both bacteria in all materials with acacia gum. Addition of acacia gum polymer to swabbing materials or filters will increase efficacy of sample collection and identification of pathogenic bacteria from locations such as hospitals or the environment. Proposed approach can also be used for long-term storage of culture collections, since acacia gum contributes to viability and stability of bacterial cultures. PMID- 22093999 TI - Molecular serogrouping of porcine enterotoxigenic Escherichia coli from Australia. AB - Enterotoxigenic Escherichia coli (ETEC) is a common etiological agent of neonatal, pre and post weaning diarrhoea in piglets. One of the most important steps in the diagnosis and epidemiological understanding of this organism is accurate serogrouping. In many instances, however, conventional serogrouping fails to produce accurate identification of serogroups. In this communication we report a modified and simplified molecular serogrouping method (rfb-RFLP) for the accurate identification of the most common porcine ETEC strains that cause neonatal, pre and post weaning diarrhoea in Australia. PMID- 22094000 TI - Flux patterns and membrane fouling propensity during desalination of seawater by forward osmosis. AB - The membrane fouling propensity of natural seawater during forward osmosis was studied. Seawater from the Red Sea was used as the feed in a forward osmosis process while a 2M sodium chloride solution was used as the draw solution. The process was conducted in a semi-batch mode under two crossflow velocities, 16.7 cm/s and 4.2 cm/s. For the first time reported, silica scaling was found to be the dominant inorganic fouling (scaling) on the surface of membrane active layer during seawater forward osmosis. Polymerization of dissolved silica was the major mechanism for the formation of silica scaling. After ten batches of seawater forward osmosis, the membrane surface was covered by a fouling layer of assorted polymerized silica clusters and natural organic matter, especially biopolymers. Moreover, the absorbed biopolymers also provided bacterial attachment sites. The accumulated organic fouling could be partially removed by water flushing while the polymerized silica was difficult to remove. The rate of flux decline was about 53% with a crossflow velocity of 16.7 cm/s while reaching more than 70% with a crossflow velocity of 4.2 cm/s. Both concentration polarization and fouling played roles in the decrease of flux. The salt rejection was stable at about 98% during seawater forward osmosis. In addition, an almost complete rejection of natural organic matter was attained. The results from this study are valuable for the design and development of a successful protocol for a pretreatment process before seawater forward osmosis and a cleaning method for fouled membranes. PMID- 22094001 TI - In-pipe water quality monitoring in water supply systems under steady and unsteady state flow conditions: a quantitative assessment. AB - Monitoring the quality of drinking water from the treatment plant to the consumers tap is critical to ensure compliance with national standards and/or WHO guideline levels. There are a number of processes and factors affecting the water quality during transmission and distribution which are little understood. A significant obstacle for gaining a detailed knowledge of various physical and chemical processes and the effect of the hydraulic conditions on the water quality deterioration within water supply systems is the lack of reliable and low cost (both capital and O & M) water quality sensors for continuous monitoring. This paper has two objectives. The first one is to present a detailed evaluation of the performance of a novel in-pipe multi-parameter sensor probe for reagent- and membrane-free continuous water quality monitoring in water supply systems. The second objective is to describe the results from experimental research which was conducted to acquire continuous water quality and high-frequency hydraulic data for the quantitative assessment of the water quality changes occurring under steady and unsteady-state flow conditions. The laboratory and field evaluation of the multi-parameter sensor probe showed that the sensors have a rapid dynamic response, average repeatability and unreliable accuracy. The uncertainties in the sensor data present significant challenges for the analysis and interpretation of the acquired data and their use for water quality modelling, decision support and control in operational systems. Notwithstanding these uncertainties, the unique data sets acquired from transmission and distribution systems demonstrated the deleterious effect of unsteady state flow conditions on various water quality parameters. These studies demonstrate: (i) the significant impact of the unsteady state hydraulic conditions on the disinfectant residual, turbidity and colour caused by the re-suspension of sediments, scouring of biofilms and tubercles from the pipe and increased mixing, and the need for further experimental research to investigate these interactions; (ii) important advances in sensor technologies which provide unique opportunities to study both the dynamic hydraulic conditions and water quality changes in operational systems. The research in these two areas is critical to better understand and manage the water quality deterioration in ageing water transmission and distribution systems. PMID- 22094002 TI - Integration of anammox into the aerobic granular sludge process for main stream wastewater treatment at ambient temperatures. AB - Anaerobic ammonium oxidation, nitrification and removal of COD was studied at ambient temperature (18 degrees C +/- 3) in an anoxic/aerobic granular sludge reactor during 390 days. The reactor was operated in a sequencing fed batch mode and was fed with acetate and ammonium containing medium with a COD/N ratio of 0.5 [g COD/gN]. During influent addition, the medium was mixed with recycled effluent which contained nitrate in order to allow acetate oxidation and nitrate reduction by anammox bacteria. In the remainder of the operational cycle the reactor was aerated and controlled at a dissolved oxygen concentration of 1.5 mg O(2)/l in order to establish simultaneous nitritation and Anammox. Fluorescent in-situ hybridization (FISH) revealed that the dominant Anammox bacterial population shifted toward Candidatus "Brocadia fulgida" which is known to be capable of organotrophic nitrate reduction. The reactor achieved stable volumetric removal rates of 900 [g N(2)-N/m(3)/day] and 600 [g COD/m(3)/day]. During the total experimental period Anammox bacteria remained dominant and the sludge production was 5 fold lower than what was expected by heterotrophic growth suggesting that consumed acetate was not used by heterotrophs. These observations show that Anammox bacteria can effectively compete for COD at ambient temperatures and can remove effectively nitrate with a limited amount of acetate. This study indicates a potential successful route toward application of Anammox in granular sludge reactors on municipal wastewater with a limited amount of COD. PMID- 22094003 TI - Defects in sensory organ morphogenesis and generation of cochlear hair cells in Gata3-deficient mouse embryos. AB - The development of the inner ear sensory epithelia involves a complex network of transcription factors and signaling pathways and the whole process is not yet entirely understood. GATA3 is a DNA-binding factor that is necessary for otic morphogenesis and without GATA3 variable defects have been observed already at early stages in mouse embryos. In the less severe phenotypes, one small oval shaped vesicle is formed whereas in the more severe cases, the otic epithelium becomes disrupted and the endolymphatic domain becomes separated from the rest of the otic epithelium. Despite these defects, the early sensory fate specification occurs in Gata3-/- otic epithelium. However, due to the early lethality of Gata3 deficient embryos, the later morphogenesis and sensory development have remained unclear. To gain information of these later processes we produced drug-rescued Gata3-/- embryos that survived up to late gestation. In these older Gata3-/- embryos, a similar variability was observed as earlier. In the more severely affected ears, the development of the separate endolymphatic domain arrested completely whereas the remaining vesicle formed an empty cavity with variable forms, but without any distinguishable otic compartments or morphologically distinct sensory organs. However, the dorsal part of this vesicle was able to adopt a sensory fate and to produce some hair cells. In the less severe cases of Gata3-/- ears, distinct utricular, saccular and cochlear compartments were present and hair cells could be detected in the vestibular sensory epithelia. Although clear cristae and maculae formed, the morphology and size of these sensory areas were abnormal and they remained often un-separated. In contrast to the vestibule, the cochlear sensory compartment remained more immature and no hair or supporting cells could be detected. Our results suggest that GATA3 is critical for normal vestibular and cochlear morphogenesis and that it is especially important for cochlear sensory differentiation. PMID- 22094005 TI - Pitfalls in extrapolating adult data to rare paediatric diseases. PMID- 22094004 TI - Meningiomas in children and adolescents: a meta-analysis of individual patient data. AB - BACKGROUND: The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined. Clinical knowledge has been drawn from small case series and extrapolation from adult studies. This study was done to pool and analyse the clinical evidence on child and adolescent meningioma. METHODS: Searches of PubMed, Medline, and Embase identified 35 case series of child and adolescent meningioma completed over the past 21 years. Individual patient data were obtained from 30 studies via direct communication with investigators. Primary outcomes were relapse-free survival (RFS) and overall survival. Prognostic variables were extent of initial surgery, use of upfront radiotherapy, age, sex, presence of neurofibromatosis, tumour location, and tumour grade. RFS and overall survival were analysed using Kaplan-Meier survival curves and multivariable Cox regression models. FINDINGS: From a total of 677 children and adolescents with meningioma, 518 were eligible for RFS analysis and 547 for overall survival analysis. Multivariable analysis showed that patients who underwent initial gross-total resection had better RFS (hazard ratio 0.16, 95% CI 0.10-0.25; p<0.0001) and overall survival (0.21, 0.11-0.39; p<0.0001) than those who had subtotal resection. No significant benefit was seen for upfront radiotherapy in terms of RFS (0.59, 0.30-1.16; p=0.128) or overall survival (1.10, 0.53-2.28; p=0.791). Patients with neurofibromatosis type 2 (NF2) had worse RFS than those without neurofibromatosis (2.36, 1.23-4.51; p=0.010). There was a significant change in overall survival with time between patients with NF2 compared with those without neurofibromatosis (1.45, 1.09-1.92; p=0.011); although overall survival was initially better for patients with NF2 than for those without neurofibromatosis, overall survival at 10 years was worse for patients with NF2. Patients with WHO grade III tumours had worse RFS than those with WHO grade I (3.90, 2.10-7.26; p<0.0001) and grade II tumours (2.49, 1.11 5.56; p=0.027). INTERPRETATION: Extent of initial surgical resection is the strongest independent prognostic factor for child and adolescent meningioma. No benefit for upfront radiotherapy was noted. Hence, aggressive surgical management, to achieve gross-total resection, is the initial treatment of choice. In the event of a subtotal resection, repeat resection is recommended to achieve maximum extirpation. Close observation is warranted for patients who have a subtotal resection or who have WHO grade III tumours. Patients without neurofibromatosis should have a minimum 10-year follow-up, whereas patients with NF2 should be considered a special risk category, necessitating life-long follow up. FUNDING: None. PMID- 22094006 TI - Using In(III) as a promoter for glycosylation. AB - InCl(3), InBr(3), and In(OTf)(3) were tested as promoters in the preparation of glycosides from trichloroacetimidate precursors. A range of protecting groups and of alcohol acceptors were used to determine the versatility of these promoters. Disaccharide formation was demonstrated. In most cases, the In(III) compounds were shown to promote glycosylation better than the widely used promoter BF(3).OEt(2). PMID- 22094007 TI - Synthesis and characterization of new polyamino-cyclodextrin materials. AB - With the aim of the synthesis of chemically modified cyclodextrins bearing polyamine pendant groups, potentially useful as capping agents for the preparation of nanosized metal systems or as auxiliaries for gene transfection, the reaction between the heptakis-(6-iodo)-(6-deoxy)-beta-cyclodextrin and various polyamines has been explored. This synthetic approach allows obtaining materials constituted by mixtures of cyclodextrins, having different degrees of substitution, which were satisfactorily characterized by means of various complementary techniques (ESI-MS, NMR, potentiometric titration). The products obtained were successfully subjected to preliminary tests for their binding abilities towards suitable organic guests and as capping agents for the preparation of stable silver nanoparticles. PMID- 22094008 TI - Determination of tranexamic acid concentration by solid phase microextraction and liquid chromatography-tandem mass spectrometry: first step to in vivo analysis. AB - A solid phase microextraction (SPME) method followed by LC-MS/MS analysis was developed to determine the concentration of tranexamic acid (TA) in plasma. The use of a new biocompatible C18 coating allowed the direct extraction from complex biological samples without prior sample preparation; no matrix effect was observed. The results revealed that SPME was suitable for the analysis of polar drugs such as TA; such an application was previously inaccessible because of the limited availability of SPME coatings that can extract polar molecules. The proposed method was validated according to the bioanalytical method validation guidelines. LOD and LLOQ were 0.5 and 1.5 MUg/ml, respectively. The recovery for the method was 0.19%, and the accuracy and precision of the method were <9 and <11%, respectively, with the exception of LLOQ, where the values were <16 and <13%, respectively. The performance of the proposed method was also compared against that of the standard techniques of protein precipitation and ultrafiltration. A statistical analysis indicated a clinically significant agreement among all assays. Another advantage of SPME over conventional techniques was the easy automation and feasibility of in vivo analysis; this advantage makes it possible to use the proposed method for an on-site analysis in clinical practice. PMID- 22094009 TI - Exploitation, vulnerability to tuberculosis and access to treatment among Uzbek labor migrants in Kazakhstan. AB - In recent years, Kazakhstan has become an important destination for primarily undocumented seasonal workers from Uzbekistan. In a context of high tuberculosis (TB) incidence, TB treatment is provided free for all residents in Kazakhstan, but migrants rarely access these services. This paper reports findings from a qualitative study conducted with migrants, TB patients and health care workers between July and September 2008 to understand the mechanisms that impede migrants' access to care. Findings describe three structural contexts--the employment, legal and health care contexts - which act in concert to render migrants vulnerable to exploitative work conditions and cause a series of barriers to health care. These conditions contribute to increased exposure to TB, heightened risk of reactivation due to weakened immunity, treatment-seeking delays, and increased severity of disease. Seasonal migration patterns also contribute to treatment interruption, which constitutes a risk for the creation of drug resistance. Using the theory of structural violence coupled with the concept of cumulative vulnerability, this paper analyzes how illegality interacts with exploitation and social marginalization to produce vulnerability to TB and restrict access to treatment. PMID- 22094010 TI - VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex. AB - BACKGROUND: The aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1. RESULTS: The examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2) and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively). The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons. CONCLUSION: The present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins. PMID- 22094011 TI - Changes of microRNAs-192, 196a and 203 correlate with Barrett's esophagus diagnosis and its progression compared to normal healthy individuals. AB - BACKGROUND: Barrett's esophagus (BE) is a disease with a rising prevalence in western countries probably due to the unhealthy lifestyle. In significant number of cases it develops to esophageal adenocarcinoma. Two decades ago, important gene regulators (microRNAs) were discovered and their attendance in the process of malignant transformation was demonstrated (e.g. miR-192, 196a, 203). Our aim was to select the patients with the increased risk of malignant transformation before the cancer develops. METHODS: 71 patients with BE disease were selected, slides from FFPE blocks were prepared, the lesions were microdissected and a qPCR relative expression analysis for selected microRNAs (generally known to be connected with malignant transformation process) was carried out. RESULTS: We demonstrated unequivocal statistically significant upregulation of two microRNAs (miR-192, 196a) and downregulation of miR-203 and positive miR-196a correlation with progression from intestinal metaplasia to adenocarcinoma compared to normal individuals. CONCLUSIONS: We hypothesize that there do exist changes of selected microRNAs which can undoubtedly distinguish the patients with BE from normal healthy individuals. PMID- 22094012 TI - Molecular and physiological aspects of alcohol dehydrogenases in the ethanol metabolism of Saccharomyces cerevisiae. AB - The physiological role and possible functional substitution of each of the five alcohol dehydrogenase (Adh) isozymes in Saccharomyces cerevisiae were investigated in five quadruple deletion mutants designated strains Q1-Q5, with the number indicating the sole intact ADH gene. Their growth in aerobic batch cultures was characterised in terms of kinetic and stoichiometric parameters. Cultivation with glucose or ethanol as carbon substrate revealed that Adh1 was the only alcohol dehydrogenase capable of efficiently catalysing the reduction of acetaldehyde to ethanol. The oxidation of produced or added ethanol could also be attributed to Adh1. Growth of strains lacking the ADH1 gene resulted in the production of glycerol as a major fermentation product, concomitant with the production of a significant amount of acetaldehyde. Strains Q2 and Q3, expressing only ADH2 or ADH3, respectively, produced ethanol from glucose, albeit less than strain Q1, and were also able to oxidise added ethanol. Strains Q4 and Q5 grew poorly on glucose and produced ethanol, but were neither able to utilise the produced ethanol nor grow on added ethanol. Transcription profiles of the ADH4 and ADH5 genes suggested that participation of these gene products in ethanol production from glucose was unlikely. PMID- 22094013 TI - The medical care costs of obesity: an instrumental variables approach. AB - This paper is the first to use the method of instrumental variables (IV) to estimate the impact of obesity on medical costs in order to address the endogeneity of weight and to reduce the bias from reporting error in weight. Models are estimated using restricted-use data from the Medical Expenditure Panel Survey for 2000-2005. The IV model, which exploits genetic variation in weight as a natural experiment, yields estimates of the impact of obesity on medical costs that are considerably higher than the estimates reported in the previous literature. For example, obesity is associated with $656 higher annual medical care costs, but the IV results indicate that obesity raises annual medical costs by $2741 (in 2005 dollars). These results imply that the previous literature has underestimated the medical costs of obesity, resulting in underestimates of the economic rationale for government intervention to reduce obesity-related externalities. PMID- 22094014 TI - Optimization and validation of liquid chromatography and headspace-gas chromatography based methods for the quantitative determination of capsaicinoids, salicylic acid, glycol monosalicylate, methyl salicylate, ethyl salicylate, camphor and l-menthol in a topical formulation. AB - Capsaicinoids, salicylic acid, methyl and ethyl salicylate, glycol monosalicylate, camphor and l-menthol are widely used in topical formulations to relieve local pain. For each separate compound or simple mixtures, quantitative analysis methods are reported. However, for a mixture containing all above mentioned active compounds, no assay methods were found. Due to the differing physicochemical characteristics, two methods were developed and optimized simultaneously. The non-volatile capsaicinoids, salicylic acid and glycol monosalicylate were analyzed with liquid chromatography following liquid-liquid extraction, whereas the volatile compounds were analyzed with static headspace gas chromatography. For the latter method, liquid paraffin was selected as compatible dilution solvent. The optimized methods were validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentrations. For both methods, peaks were well separated without interference of other compounds. Linear relationships were demonstrated with R2 values higher than 0.996 for all compounds. Accuracy was assessed by performing replicate recovery experiments with spiked blank samples. Mean recovery values were all between 98% and 102%. Precision was checked at three levels: system repeatability, method precision and intermediate precision. Both methods were found to be acceptably precise at all three levels. Finally, the method was successfully applied to the analysis of some real samples (cutaneous sticks). PMID- 22094016 TI - An assessment of burn injury hospitalisations of adolescents and young adults in Western Australia, 1983-2008. AB - BACKGROUND: This study presents a 26-year epidemiological assessment of burn injury hospitalisations for people 15-29 years of age in Western Australia. METHODS: Linked hospital morbidity and death data for all persons hospitalised with an index burn injury in Western Australia for the period 1983-2008 were analyzed. Annual age-specific incidence rates were estimated. Poisson regression analyses were used to estimate temporal trends in hospital admissions. RESULTS: There were 6404 burn hospital admissions of which 76% were male. Males had hospitalisation rates 3.0 times that of females (95%CI: 2.8-3.2) and Aboriginal people had rates 2.3 times (95%CI: 2.1-2.5) that of non-Aboriginal persons. Hospitalisations for burn injury declined by 42% (95%CI: 35-47) for males and 21% (95%CI: 6-33) for females. Hospitalisations declined by 53% (95%CI: 35-63) for Aboriginal people, and by 35% (95%CI: 29-41) for non-Aboriginal people. Significant reductions were observed for flame and electrical burn hospitalisations. The major causes of burns in males were exposure to controlled fires and ignition of inflammable materials, with scalds the predominant cause of burn in females. CONCLUSIONS: Downward trends in burn injury hospitalisations for both males and females 15-29 years of age were observed; however, males and Aboriginal persons have significantly elevated hospitalisation rates. PMID- 22094017 TI - Distinct phases of Wnt/beta-catenin signaling direct cardiomyocyte formation in zebrafish. AB - Normal heart formation requires reiterative phases of canonical Wnt/beta-catenin (Wnt) signaling. Understanding the mechanisms by which Wnt signaling directs cardiomyocyte (CM) formation in vivo is critical to being able to precisely direct differentiated CMs from stem cells in vitro. Here, we investigate the roles of Wnt signaling in zebrafish CM formation using heat-shock inducible transgenes that increase and decrease Wnt signaling. We find that there are three phases during which CM formation is sensitive to modulation of Wnt signaling through the first 24 h of development. In addition to the previously recognized roles for Wnt signaling during mesoderm specification and in the pre-cardiac mesoderm, we find a previously unrecognized role during CM differentiation where Wnt signaling is necessary and sufficient to promote the differentiation of additional atrial cells. We also extend the previous studies of the roles of Wnt signaling during mesoderm specification and in pre-cardiac mesoderm. Importantly, in pre-cardiac mesoderm we define a new mechanism where Wnt signaling is sufficient to prevent CM differentiation, in contrast to a proposed role in inhibiting cardiac progenitor (CP) specification. The inability of the CPs to differentiate appears to lead to cell death through a p53/Caspase-3 independent mechanism. Together with a report for an even later role for Wnt signaling in restricting proliferation of differentiated ventricular CMs, our results indicate that during the first 3days of development in zebrafish there are four distinct phases during which CMs are sensitive to Wnt signaling. PMID- 22094018 TI - Disruption of Eaat2b, a glutamate transporter, results in abnormal motor behaviors in developing zebrafish. AB - Analysis of zebrafish mutants that have defects in motor behavior can allow entree into the hindbrain and spinal cord networks that control locomotion. Here, we report that zebrafish techno trousers (tnt) locomotor mutants harbor a mutation in slc1a2b, which encodes Eaat2b, a plasma membrane glutamate transporter. We used tnt mutants to explore the effects of impaired glutamate transporter activity on locomotor network function. Wild-type larvae perform robust swimming behavior in response to touch stimuli at two and four days after fertilization. In contrast, tnt mutant larvae demonstrate aberrant, exaggerated body bends beginning two days after fertilization and they are almost paralyzed four days after fertilization. We show that slc1a2b is expressed in glial cells in a dynamic fashion across development, which may explain the abnormal sequence of motor behaviors demonstrated by tnt mutants. We also show that tnt larvae demonstrate enhanced excitation of neurons, consistent with the predicted effects of excessive glutamate. These findings illustrate the dynamic regulation and importance of glutamate transporters during development. Since glutamate toxicity caused by EAAT2 dysfunction is thought to promote several different neurological disorders in humans, including epilepsy and neurodegenerative diseases, tnt mutants hold promise as a new tool to better understand these pathologies. PMID- 22094020 TI - [From image-guided radiotherapy to dose-guided radiotherapy]. AB - PURPOSE: In case of tumour displacement, image-guided radiotherapy (IGRT) based on the use of cone beam CT (tomographie conique) allows replacing the tumour under the accelerator by rigid registration. Anatomical deformations require however replanning, involving an estimation of the cumulative dose, session after session. This is the objective of this study. PATIENTS AND METHODS: Two examples of arc-intensity modulated radiotherapy are presented: a case of prostate cancer (total dose=80 Gy) with tomographie conique (daily prostate registration) and one head and neck cancer (70 Gy). For the head and neck cancer, the patient had a weekly scanner allowing a dose distribution calculation. The cumulative dose was calculated per voxel on the planning CT after deformation of the dose distribution (with trilinear interpolation) following the transformation given by a non-rigid registration step (Demons registration method) from: either the tomographie conique (prostate), or the weekly CT. The cumulative dose was eventually compared with the planned dose. RESULTS: In cases of prostate irradiation, the "cumulative" dose corresponded to the planned dose to the prostate. At the last week of irradiation, it was above the planned dose for the rectum and bladder. The volume of rectal wall receiving more than 50 Gy (V50) was 20% at the planning and 26% at the end of treatment, increasing the risk of rectal toxicity (NTCP) of 14%. For the bladder wall, V50 were 73% and 82%, respectively. In head and neck, the "cumulative" dose to the parotid exceeded the planned dose (mean dose increasing from 46 Gy to 54 Gy) from the 5th week of irradiation on, suggesting the need for replanning within the first 5 weeks of radiotherapy. CONCLUSION: The deformable registration estimates the cumulative dose delivered in the different anatomical structures. Validation on digital and physical phantoms is however required before clinical evaluation. PMID- 22094019 TI - Conditional hypoxia inducible factor-1alpha induction in embryonic pulmonary epithelium impairs maturation and augments lymphangiogenesis. AB - Hypoxia inducible factor (HIF) 1a, EPAS1 and NEPAS are expressed in the embryonic mouse lung and each isoform exhibits distinct spatiotemporal expression patterns throughout morphogenesis. To further assess the role of the HIF1a isoform in lung epithelial cell differentiation and homeostasis, we created transgenic mice that express a constitutively active isoform of human HIF-1a (HIF-1a three point mutant (TPM)), in a doxycycline-dependent manner. Expression of HIF1a TPM in the developing pulmonary epithelium resulted in lung hypoplasia characterized by defective branching morphogenesis, altered cellular energetics and impaired epithelial maturation, culminating in neonatal lethality at birth from severe respiratory distress. Histological and biochemical analyses revealed expanded glycogen pools in the pulmonary epithelial cells at E18.5, concomitant with decreased pulmonary surfactant, suggesting a delay or an arrest in maturation. Importantly, these defects occurred in the absence of apoptosis or necrosis. In addition, sub-pleural hemorrhaging was evident as early as E14.5 in HIF1a TPM lungs, despite normal patterning of the blood vasculature, consistent with defects in endothelial barrier function. Epithelial expression of HIF1a TPM also resulted in increased VEGFA and VEGFC production, an increase in the number of lymphatic vessels and indirect activation of the multiple Notch pathway components in endothelial precursor cells. Collectively, these data indicate that HIF-1a protein levels in the pulmonary epithelium must be tightly controlled for proper development of the epithelial and mesenchymal compartments. PMID- 22094021 TI - Image processing and lattice determination for three-dimensional nanocrystals. AB - Three-dimensional nanocrystals can be studied by electron diffraction using transmission cryo-electron microscopy. For molecular structure determination of proteins, such nanosized crystalline samples are out of reach for traditional single-crystal X-ray crystallography. For the study of materials that are not sensitive to the electron beam, software has been developed for determining the crystal lattice and orientation parameters. These methods require radiation-hard materials that survive careful orienting of the crystals and measuring diffraction of one and the same crystal from different, but known directions. However, as such methods can only deal with well-oriented crystalline samples, a problem exists for three-dimensional (3D) crystals of proteins and other radiation sensitive materials that do not survive careful rotational alignment in the electron microscope. Here, we discuss our newly released software AMP that can deal with nonoriented diffraction patterns, and we discuss the progress of our new preprocessing program that uses autocorrelation patterns of diffraction images for lattice determination and indexing of 3D nanocrystals. PMID- 22094022 TI - Factors predicting deviation from an enhanced recovery programme and delayed discharge after laparoscopic colorectal surgery. AB - AIM: The study aimed to identify factors that predict postoperative deviation from an enhanced recovery programme (ERP) and/or delayed discharge following colorectal surgery. METHOD: Data were prospectively collected from all patients undergoing elective laparoscopic colorectal resection between January 2006 and December 2009. They included Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) variables, body mass index (BMI), sex, preoperative serum albumin, pathology, conversion from a laparoscopic to an open approach and postoperative length of hospital stay. RESULTS: There were 176 patients (90 women) of mean age 68 years. Fifteen (9%) operations were converted from laparoscopic to open. The remainder were completed laparoscopically. Fifty five (31%) deviated from the ERP, with most failing multiple elements. The most common reason was failure to mobilize, which often occurred in conjunction with paralytic ileus or analgesic failure. Factors independently predicting ERP deviation on multivariate analysis were pathology and intra-operative complications. The median length of stay was 5 days. Sixty-four (36%) patients had a prolonged length of stay that was predicted by age, number of procedures and ERP deviation. CONCLUSION: Pathology and intra-operative complications are independent predictors of ERP deviation. Prolonged length of stay can be predicted by age, multiple procedures and ERP deviation. Failure to mobilize should be considered as a red flag sign prompting further investigation following colorectal resection. PMID- 22094023 TI - An indwelling urinary catheter for the 21st century. AB - What's known on the subject? and What does the study add? A vast literature has been published on the prevalence, morbidity and microbiology of catheter associated urinary tract infections. Research and development in recent years has focused on producing antibacterial coatings for the indwelling Foley catheter with insufficient attention to its design. This article provides a critical examination of the design of the indwelling Foley catheter. Design specifications are outlined for a urine collection device that should reduce the vulnerability of catheterised urinary tract to infection. The indwelling urinary catheter is the most common cause of infections in hospitals and other healthcare facilities [1]. As long ago as 1958, Paul Beeson [2] warned '... the decision to use this instrument should be made with the knowledge that it involves the risk of producing a serious disease which is often difficult to treat'. Since then, scientific studies have progressed revealing a greater understanding of the bladder's defence mechanisms against infection and how they are undermined by the Foley catheter [3-5]. In addition, the complications caused by the development of bacterial biofilms on catheters have been recognised and the ways in which these bacterial communities develop on catheters have become clear [5,6]. It is now obvious that fundamental problems with the basic design of the catheter, which has changed little since it was introduced into urological practice by Dr Fredricc Foley in 1937 [7], induce susceptibility to infection. These issues need to be addressed urgently if we are to produce a device suitable for use in the 21st century. PMID- 22094024 TI - Primary sclerosing cholangitis and disease distribution in inflammatory bowel disease. AB - BACKGROUND & AIMS: The relationship between site of intestinal inflammation and primary sclerosing cholangitis (PSC) development in inflammatory bowel disease (IBD) has not been studied extensively, but may be important in understanding the pathogenesis of PSC. We aimed to determine patterns of disease distribution in IBD patients with and without PSC. METHODS: We performed a 2-part study involving the following: (1) 2754 IBD patients and (2) 82 separate PSC patients attending the Irish National Liver Transplant Unit. RESULTS: Fifty-nine of 2708 (2.2%) IBD patients had PSC. In ulcerative colitis patients, PSC incidence increased with increasing colonic involvement (P = .001) and was relatively rare in those without total colitis. Thirteen Crohn's disease patients had PSC, none with isolated small-bowel disease had PSC (P = .03). In study 2, the majority of ulcerative colitis patients with PSC had total colitis, whereas the remainder had disease extending at least to the left colon. In addition, all 10 PSC patients with Crohn's disease had colonic involvement. CONCLUSIONS: An inflamed colon, but not small bowel, is important in PSC development and it is possible that bacterial translocation and subsequent portal bacteremia is important in PSC development in IBD. PMID- 22094025 TI - Role of albumin treatment in patients with spontaneous bacterial peritonitis. AB - BACKGROUND & AIMS: Intravenous administration of albumin decreases the incidence of renal failure and mortality among patients with spontaneous bacterial peritonitis (SBP). However, it is unclear whether it should be given to all patients with SBP; we evaluated its efficacy. METHODS: We analyzed data from all episodes of SBP (n = 216) during a 7-year period that occurred in a nonselected series of 167 patients with cirrhosis. Low-risk episodes (urea <11 mmol/L and bilirubin <68 MUmol/L) were not treated with albumin, whereas high-risk episodes (urea >11 mmol/L and/or bilirubin >68 MUmol/L) were or were not given albumin at the discretion of the attending physician. RESULTS: Sixty-four episodes of SBP (29.6%) were low risk and not treated with albumin, whereas 152 (70.4%) were high risk; 73 of these (48%) were treated with albumin and 79 (52%) were not. Renal failure before SBP resolution was less frequent after low-risk episodes than high risk episodes (4.7% versus 25.6%; P = .001), in-hospital mortality was lower (3.1% versus 38.2%; P < .001), and the 3-month probability of survival was higher (93% versus 53%; P < .001). In an analysis of only the high-risk group, patients who received albumin had lower in-hospital mortality than those not treated with albumin (28.8% versus 46.8%; P = .02) and a greater 3-month probability of survival (62% versus 45%; P = .01). CONCLUSIONS: Albumin therapy increases survival of patients who have high-risk episodes of SBP, although it does not seem to be necessary for patients with low risk of death. PMID- 22094026 TI - What to do with my ambulatory surgery center. PMID- 22094027 TI - Dirlotapide as a model substrate to refine structure-based drug design strategies on CYP3A4-catalyzed metabolism. AB - Multiple crystal structures of CYP3A4 bound with various substrates or inhibitors have been used as templates for docking of new chemical entities to predict sites of metabolism and molecular interactions for drug design. Herein, modeling studies with dirlotapide, a CYP3A4 substrate, indicated that a substantial conformational change of CYP3A4 was necessary to accommodate it within the active site cavity, which is in good agreement with a new published CYP3A4 ritonavir co crystal structure. Thus, the importance of considering the substrate-induced conformational change in CYP3A4, thermochemical properties of reaction centers, and essential in vitro experimental data support were analyzed for the refinement of computational models. PMID- 22094028 TI - Lead optimisation of pyrazoles as novel FPR1 antagonists. AB - Optimisation of a series of pyrazole inhibitors of the human FPR1 receptor has been achieved. The use of an in vitro media loss assay was utilised to identify sub-series with more robust DMPK profiles. These were subsequently improved to generate analogues with attractive overall profiles. PMID- 22094029 TI - [The surgical option of degenerative cervical spinal stenosis]. PMID- 22094030 TI - [One-stage posterior approach spinal reconstruction for severe lumbar burst fracture]. AB - OBJECTIVE: To evaluate the clinical therapeutic outcomes for severe burst fracture of lumbar vertebrae via a posterior approach for one-stage spinal "three column" reconstruction. METHODS: An retrospective analysis of data was performed for 21 patients with severe burst fracture of lumbar vertebrae undergoing a posterior approach for one-stage spinal "three-column" reconstruction from 2005 to 2010. It was compared with previous 15 cases undergoing a staged anteroposterior approach. The operative duration, volume of blood loss, pre- and post-operative imaging measurements of kyphosis and vertebral height and nerve function recovery were evaluated. RESULTS: The values of operative duration and volume of blood loss in the one-stage posterior approach group were significantly less than those of the two-stage anteroposterior approach group [(263 +/- 72) min vs (439 +/- 75) min, t = -5.303, P < 0.01; (1143 +/- 296) ml vs (1471 +/- 399) ml, t = -2.169, P = 0.042)]. Statistical significance existed in postoperative kyphosis between two groups [(0.5 +/- 2.0) degrees vs (3.9 +/- 2.6) degrees , t = -3.336, P = 0.003]. Vertebral height had no statistical significance pre- and post-operatively between two groups while restoration of vertebral height did [(0.47 +/- 0.19) mm vs (0.26 +/- 0.15) mm, t = 2.669, P = 0.015]. CONCLUSION: Posterior approach for one-stage vertebral resection, mesh implantation, pedicle screws and rod internal fixation for reconstructing spinal "three-column" structures offers excellent feasibility and safety. And it may avoid complications associated with an anteroposterior approach for two-stage procedures. The median length of hospital stay is also reduced. PMID- 22094031 TI - [Lateral position one-stage combined posteroanterior approaches for the treatment of lumbosacral tuberculous spondylitis]. AB - OBJECTIVE: To investigate the feasibility of a one-stage combined posteroanterior approaches for the treatment of lumbosacral tuberculous spondylitis with the patients lying in a lateral position. METHODS: A retrospective review was conducted for 15 patients with lumbosacral tuberculosis undergoing one-stage combined posteroanterior approaches for radical lesion resection and reconstruction. All patients were observed and evaluated by clinical and imaging studies. RESULTS: Operative posture:11 cases for right side and 4 cases for left side. The mean operative duration was 280 min (range: 230 - 380 min) and the mean estimated volume of blood loss 1720 ml (range: 1100 - 3000 ml). Imaging results: No recurrence of tuberculose focus was found until the last follow-up. Upon image reviewing, it showed no loosening or displacement except for two cases of slightly collapsed titanium mesh. Preoperative and postoperative changes in the degree of lumbar lordosis were statistically significant [(20 +/- 5) degrees vs (31 +/- 5) degrees , P < 0.05]. The Kirkaldy-Willis classification rating yielded satisfactory results for 13 cases. CONCLUSION: The patients with lumbosacral tuberculosis undergoing one-stage combined posteroanterior approaches may achieve radical lesion resection, posteroanterior collaboration and reconstruction. It avoids a 2-stage operation, eliminates the need of changing a patient's body position with secondary sterilization and shortens the operative duration. Lumbosacral surgery for tuberculosis combines the respective advantages of anterior, posterior and combined posteroanterior approaches and yet makes up for their deficiencies. PMID- 22094032 TI - [Treatment of combination atlantoaxial fractures with posterior fusion plus atlantoaxial pedicle screw]. AB - OBJECTIVE: To explore the clinical feasibility, approach, efficacy and indications of posterior fusion plus pedicle screw fixation in the treatment of combination atlantoaxial fractures. METHODS: A retrospective analysis was conducted for 26 cases of Jefferson and dens fracture treated with atlantoaxial pedicle screw from June 2008 to May 2010. RESULTS: The postoperative radiographs verified an excellent position of all screws with a satisfactory atlantoaxial reduction. Operative time was (126 +/- 26) min, and blood loss was (350 +/- 107) ml. During an average follow-up period of 14 months (range: 6 - 28), it showed no spine cord and vertebral artery injury or interfixation failure. Atlantoaxial alignment and stability were restored without any instrumentation-related complication. CONCLUSION: Posterior atlantoaxial pedicle screw and rod fixation may provide immediate three-dimensional rigid fixation of atlantoaxial joint. This technique is more effective than other previously reported approaches. PMID- 22094033 TI - [Building an effective nonlinear three-dimensional finite-element model of human thoracolumbar spine]. AB - OBJECTIVE: To build an effective nonlinear three-dimensional finite-element (FE) model of T(11)-L(3) segments for a further biomechanical study of thoracolumbar spine. METHODS: The CT (computed tomography) scan images of healthy adult T(11) L(3) segments were imported into software Simpleware 2.0 to generate a triangular mesh model. Using software Geomagic 8 for model repair and optimization, a solid model was generated into the finite element software Abaqus 6.9. The reasonable element C3D8 was selected for bone structures. Created between bony endplates, the intervertebral disc was subdivided into nucleus pulposus and annulus fibrosus (44% nucleus, 56% annulus). The nucleus was filled with 5 layers of 8-node solid elements and annulus reinforced by 8 crisscross collagenous fiber layers. The nucleus and annulus were meshed by C3D8RH while the collagen fibers meshed by two node-truss elements. The anterior (ALL) and posterior (PLL) longitudinal ligaments, flavum (FL), supraspinous (SSL), interspinous (ISL) and intertransverse (ITL) ligaments were modeled with S4R shell elements while capsular ligament (CL) was modeled with 3-node shell element. All surrounding ligaments were represented by envelope of 1 mm uniform thickness. The discs and bone structures were modeled with hyper-elastic and elasto-plastic material laws respectively while the ligaments governed by visco-elastic material law. The nonlinear three-dimensional finite-element model of T(11)-L(3) segments was generated and its efficacy verified through validating the geometric similarity and disc load-displacement and stress distribution under the impact of violence. Using ABAQUS/ EXPLICIT 6.9 the explicit dynamic finite element solver, the impact test was simulated in vitro. RESULTS: In this study, a 3-dimensional, nonlinear FE model including 5 vertebrae, 4 intervertebral discs and 7 ligaments consisted of 78 887 elements and 71 939 nodes. The model had good geometric similarity under the same conditions. The results of FEM intervertebral disc load displacement curve were similar to those of in vitro test. The stress distribution results of vertebral cortical bone, posterior complex and cancellous bone were similar to those of other static experiments in a dynamic impact test under the observation of stress cloud. CONCLUSION: With the advantages of high geometric and mechanical similarity and complete thoracolumbar, hexahedral meshes, nonlinear finite element model may facilitate the impact loading test for a further dynamic analysis of injury mechanism for thoracolumbar burst fracture. PMID- 22094034 TI - [Altered expression of endogenous transforming growth factor beta1 and early calcification related genes in rat endplate]. AB - OBJECTIVE: To explore the relationship between endogenous transforming growth factor (TGF)-beta1 and calcification-related genes through an in vitro degeneration model by propagating rat endplate chondrocytes during a natural degeneration process. METHODS: Endplate chondrocytes were extracted from rat lumbar vertebrae, isolated by enzyme digestion and P2 and P4 generations selected for a 6-day in vitro culture. The specimens were photographed microscopically to observe the cellular differences by alizarin red staining. Type II collagen marker gene, transcription factor SOX-9 gene and metabolism-related genes proteoglycan. matrix metalloproteinase (MMP)-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 were detected by RT-PCR to verify the degeneration model. Based on this model, the changes of growth factor TGF-beta1 and calcification-related genes ankyrin (ANK), ectonucleotide pyrophosphatase (ENPP), tissue-nonspecific alkaline phosphatase (TNAP) were continuously tested. RESULTS: Compared with P2 cells, P4 cells tended to assume a spindle-shaped morphology. And alizarin red staining showed no change between them. The level of transcription factor SOX-9 of P4 cells (P4/P2 = 0.0690, P = 0.0489) was significantly lower than that of P2 cells. Type II collagen (P4/P2 = 0.0535, P = 0.009) and proteoglycan (P4/P2 = 0.2672, P = 0.0343) were also significantly lower than those of P2 cells. No significant changes were observed in other metabolism-related genes. TGF-beta1 (P4/P2 = 0.5934, P = 0.0482) was significantly lower. The expressions of TNAP (P4/P2 = 0.0385, P = 0.0139) and ANK (P4/P2 = 0.2121, P = 0.0009) were significantly lower. But ENPP showed no significant change. CONCLUSION: P4 endplate chondrocytes undergo natural degeneration in vitro with the rising passage number. Type II collagen, SOX-9 and proteoglycan are significantly reduced. Endogenous TGF-beta1 gene and calcification-related genes are down-regulated. The decrease of ANK gene may be caused by the down-regulation of endogenous TGF beta1. Modulating the expression of endogenous TGF-beta1 gene in endplate chondrocytes may become a new therapeutic approach for the degeneration of intervertebral disc. PMID- 22094035 TI - [Diffusion tensor imaging findings in first-episode and chronic schizophrenics]. AB - OBJECTIVE: To investigate the integrity of white matters in first-episode and chronic schizophrenics. METHODS: For this study, 39 first-episode and 38 chronic schizophrenics, 69 healthy controls (age, gender and years of received education no significantly different from those of the patients) underwent diffusion weighted images with a single-shot echo planar imaging (EPI) sequence aligned to the straight axial plane. The fractional anisotropy (FA) images of three groups underwent one-way ANOVA with the methods of voxel-based morphometric (VBM) analysis. RESULTS: (1) There were three brain regions where the FA values of white matter were different among three groups: right caudate nucleus (MNI: 20, 12, 14; cluster = 432 voxels; FA value: 0.36 +/- 0.18 vs 0.35 +/- 0.24 vs 0.38 +/ 0.17), left insula (MNI: -32, 18, 2; cluster = 204 voxels; FA value: 0.35 +/- 0.31 vs 0.33 +/- 0.24 vs 0.36 +/- 0.21) and right anterior cingulate (MNI: 16, 36, 12; cluster = 132 voxels; FA value: 0.35 +/- 0.29 vs 0.34 +/- 0.31 vs 0.37 +/ 0.25). (2) The mean FA values of the three brain regions of two patients groups decreased versus those of healthy controls (P < 0.05). (3) The mean FA values of left insular region in chronic patients decreased versus those of the first episode patients (P < 0.05). CONCLUSION: The reduced integrity of white matter may play an etiological role in schizophrenia and the changes are probably progressive. PMID- 22094036 TI - [Transcatheter arterial chemoembolization plus percutaneous thermal ablation in large hepatocellular carcinoma: clinical observation of efficacy and predictors of prognostic factors]. AB - OBJECTIVE: To explore the technical success rate, efficacy, overall survival, recurrence-free survival and prognostic factors of transcatheter arterial chemoembolization (TACE) plus thermal ablations of radiofrequency ablation (RFA) and microwave ablation (MWA) in the patients with large hepatocellular carcinoma (HCC). METHODS: Forty-five cases with Child-pugh class A, B cirrhosis and large HCC with a maximum tumor between 5.0 cm to 10.0 cm underwent TACE and thermal ablation. Twenty-five patients received TACE plus RFA while the other 20 patients underwent TACE plus MWA. Their efficacy, long-term survival and prognostic factors were statistically analyzed. RESULTS: TACE plus thermal ablation were performed in 84 tumors with a successful rate of 100% (86/86) and a complete ablation rate of 94.0% (79/84). The major complication rate was 6.7% (3/45). Local and distant recurrence rates were 66.7% (30/45) and 71.1% (32/45) respectively. The 1 and 2-year recurrence-free survival rates were 26.7% (12/45) and 13.3% (6/45). And the 1, 2 and 3-year survival rates were 80.0% (36/45), 33.3% (15/45) and 6.7% (3/45) respectively. Univariate and Cox regression analyses indicated that tumor size > 7.0 cm, multi-nodularity, incomplete necrosis and pretherapy alpha-fetoprotein (AFP) >= 200 ug/L were 4 unfavorable prognostic factors for the long-term survival. CONCLUSION: The combined procedures of TACE and percutaneous thermal ablation are both safe and effective for the unresectable large HCC (> 5.0 cm). It represents an alleviate treatment for those patients with tumor size > 7.0 cm. Tumor size, tumor number, completeness of necrosis and AFP level are all significant prognostic factors. PMID- 22094037 TI - [Comparison of effects in puerpera and fetus with ephedrine and phenylephrine during a cesarean delivery]. AB - OBJECTIVE: To compare the different effects in fetus and puerpera with an equivalent dose of ephedrine (E) and phenylephrine (Ph) for maintaining maternal blood pressure near baseline during spinal anesthesia for a cesarean delivery. METHODS: Ninety mature parturient women with single-embryo scheduled for an elective cesarean delivery under spinal anesthesia at our hospital during January June 2010 were randomly divided into 3 groups (E, E + Ph and Ph, n = 30 each). Group E received an infusion of ephedrine (ephedrine 4 g/L), Group E + Ph ephedrine plus phenylephrine (ephedrine 2 g/L + phenylephrine 25 mg/L) and Group Ph phenylephrine (phenylephrine 50 mg/L). The blood pressure was maintained near baseline by adjusting the infusion rate during anesthesia. The maternal blood pressure, heart rate and fetal heart rate were measured at the time points of 1, 3, 5 and 10 min, skin incision and uterine incision after injecting anesthetic into subarachnoid space. Immediately after delivery, maternal arterial, umbilical arterial and umbilical venous blood samples were withdrawn for the measurements of blood gases and plasma concentrations of lactate and glucose. RESULTS: The fetal heart rate of groups E and E + Ph significantly increased after infusion [5 min: (150 +/- 10) times/min vs (142 +/- 13) times/min, (146 +/- 10) times/min vs (142 +/- 9) times/min, both P < 0.05] while those of group Ph had no significant changes [5 min: (143 +/- 9) times/min vs(143 +/- 6) times/min, P > 0.05]. The incidence of fetal tachycardia in groups E and E + Ph was greater than that in group Ph. In group E, umbilical arterial and umbilical venous pH and base excess were lower than those in groups E + Ph and Ph [umbilical arterial: 7.20 +/- 0.10 vs 7.27 +/- 0.05, 7.28 +/- 0.03, (-3.1 +/- 3.1) mmol/L vs (-0.9 +/- 1.7) mmol/L, (-0.3 +/- 1.7) mmol/L, umbilical venous:7.29 +/- 0.09 vs 7.34 +/- 0.03, 7.34 +/- 0.03, (-3.3 +/- 2.9) mmol/L vs (-2.0 +/- 1.7) mmol/L, (-0.9 +/- 1.5) mmol/L, all P < 0.05]. Umbilical arterial PCO2 and plasma concentrations of lactate and glucose in group E were greater than those in group Ph (all P < 0.05). Umbilical arterial and umbilical venous plasma concentrations of lactate and glucose were greater in group E + Ph than those in group Ph (all P < 0.05). But base excess was lower (P < 0.05). CONCLUSION: Phenylephrine may be more ideal for treating the hypotension of spinal anesthesia for a cesarean delivery. It corrects hypotension following spinal anesthesia, improves fetal oxygen supply and demand balance but induces no metabolic excitation in fetus as compared with ephedrine. PMID- 22094038 TI - [Effects of incretion hormones on growth pituitary adenoma ectomy and evaluation of long-term therapeutic efficacy]. AB - OBJECTIVE: To investigate the effect of incretion hormones on growth pituitary adenoma ectomy patients and evaluate its long-term therapeutic efficacy. METHODS: A total of 38 growth pituitary adenoma patients were treated by adenoma ectomy between 2002 to 2009 at our hospital. The dynamic concentrations of serum prolactin (PRL), growth hormone (GH), cortisone, adrenocorticotrophic hormone (ACTH) and thyroid function (T3, T4 & thyroid-stimulating hormone) were monitored before and after microsurgery. All cases had been followed up for over one year to evaluate the long-term therapeutic efficacy. RESULTS: The level of GH decreased markedly within one week after ectomy [(2.49 +/- 0.22) ug/L vs (9.24 +/ 0.56) ug/L, P < 0.05] and remained stable afterwards. Among 22 cases of GH secreting pituitary adenoma with total removal, the post-operative level of GH dropped below 2.5 ug/L in 11 cases but the other 11 cases did not. And 3 cases were recurrent within 3 years post-operation. CONCLUSIONS: The GH level at Week 1 post-operation is one of the major indicators for evaluating the efficacy of surgery. And the level of GH dropping below 2.5 ug/L at Week 1 post-operation may be used as a standard for clinical cure. PMID- 22094039 TI - [Endovascular treatment of ruptured intracranial very small aneurysms]. AB - OBJECTIVE: To explore the technique of endovascular therapy for ruptured intracranial very small aneurysms and evaluate the feasibility and safety of endovascular treatment of such aneurysms. METHODS: Twenty-two intracranial very small aneurysms in 22 patients with subarachnoid hemorrhage undergoing endovascular therapy were reviewed retrospectively. Their clinical, imaging, interventional and follow-up data were analyzed. Among them, there were 13 males and 9 females with a mean age of 54.5 years old. The Hunt-Hess grade was as follows: Grades I and II (n = 12) and Grades III and IV (n = 10). The locations of aneurysms were as follows: anterior communicating artery (n = 7), middle cerebral artery (n = 2), posterior communicating artery (n = 8) and internal carotid artery (n = 5). All aneurysms were embolized with coils. Among them, 7 received stent assistance and 2 balloon remodeling. RESULTS: Among 22 coiled aneurysms, complete occlusion was achieved in 17 aneurysms, neck remnant occurred in 1 patient and aneurysm remnant in 4 patients. Two aneurysms ruptured during coiling and one patient died from it. One patient had transient hemiparesis. All patients received a follow-up of 3 - 36 months and there was no recurrent hemorrhage. CONCLUSION: Endovascular treatment of ruptured intracranial very small aneurysms seems to be technically feasible, relatively safe and practically effective. An appropriate selection of interventional materials and use of sophisticated techniques yield an excellent outcome. PMID- 22094040 TI - [Clinical study of cryoablation in the salvage treatment of stage III non-small cell lung cancer]. AB - OBJECTIVE: To evaluate the efficacy and safety of argon-helium cryoablation as a salvage therapy for the failure cases of non-small cell lung cancer (NSCLC) after radiochemotherapy. METHODS: A total of 12 NSCLC patients (stage III) with a diagnosis of recurrence after radiochemotherapy received cryoablation. The endpoint objectives were overall response rate (RR), clinical benefit rate (CBR), 1-year survival rate, quality of life (QOL) and safety profile. RESULTS: Among them, the overall response rate was 6/12 cases and the clinical benefit rate 7/12 cases at 12 months post-cryoablation. The 1-year survival rate was 10/12 cases. No significant complications or adverse reactions occurred during the process of cryoablation. As shown by the QOL score, the quality of life was satisfactory. CONCLUSION: As a salvage treatment for the recurrence NSCLC cases after radiochemotherapy, cryoablation may achieve a high response rate, a favorable 1 year survival rate and a high safety profile. It has excellent prospects for clinical applications. PMID- 22094041 TI - [Analysis of low-quality embryo transfer strategy in in vitro fertilization and embryo transfer cycle]. AB - OBJECTIVE: To investigate the transfer strategy of low-quality embryo in in vitro fertilization and embryo transfer (IVF-ET) cycle. METHODS: A retrospective analysis was performed for the clinical data of 621 IVF-ET cycles under controlled ovarian hyperstimulation, including 574 fresh embryo transfer (ET) cycles (Group T1) and 47 frozen-thawed embryo transfer (FET) as the first ET cycles (Group C1). Logistic regression was used to model the probability of clinical pregnancy rate based on the cycle-specific factors. RESULTS: The clinical pregnancy rate was significantly higher in Group C1 than Group T1 [38.3% (18/47) vs 22.1% (127/574), P < 0.05]. Multivariate logistic regression analysis revealed that patient age and ET method were significantly associated with the clinical pregnancy rate. After adjusting for patient age, the clinical pregnancy rate remained significantly higher in Group C1 than Group T1 (OR: 2.107, 95%CI: 1.128 - 3.939, P < 0.05). CONCLUSION: The use of FET instead of fresh ET may improve the clinical pregnancy rate in low-quality embryo cycles. PMID- 22094042 TI - [Expression of bone morphogenetic protein receptor 2 in myocardialization of cardiac proximal outflow tract septum in connexin 43 knockout embryonic mice]. AB - OBJECTIVE: To investigate the mechanism of myocardialization of proximal outflow tract septum and its effect on the conotruncal anomaly in mice. METHODS: The C(57)/BL(6) mice of embryonic day (E) 11.5 - 16.5 were selected. The phenotypes of connexin 43 (Cx43) homozygotes (Cx43(-/-)), heterozygotes (Cx43(+/-)) and wild types (Cx43(+/+)) were genetically typed by polymerase chain reaction (PCR). Bone morphogenetic protein receptor 2 (Bmpr2) and alpha-sarcomeric acti (alpha-SCA) were detected by immunohistochemistry. RESULTS: The expression of alpha-SCA in the proximal outflow tract (OFT) septum was delayed obviously in Cx43(-/-) predominantly at E13.5 and E14.5. From E11.5 to E13.5, the expression of Bmpr2 was detected in cardiac atrium and epicardium of Cx43(+/+) fetal heart. And Bmpr2 was slightly expressed in ventricular muscle of Cx43(+/+) fetal heart. And it was expressed slightly only in cardiac atrium and epicardium of Cx43(+/-) and Cx43(-/ ) fetal heart. From E14.5 to E16.5, its expression was detected obviously in cardiac atrium, epicardium, endocardium, trabeculum, ventricular muscle and OFT septum of Cx43(+/+) fetal heart. At E14.5, its expression was detected obviously in cardiac atrium, epicardium, endocardium and trabeculum of Cx43(+/-) and Cx43( /-) fetal heart while none in ventricular muscle and OFT septum. At E15.5 and E16.5, its expression was detected obviously in cardiac atrium, epicardium, endocardium, trabeculum, ventricular muscle and OFT septum of Cx43(+/-) and Cx43( /-) fetal heart. Its expression was also detected obviously in OFT septum of Cx43(+/-) and Cx43(-/-) fetal heart with incomplete myocardialization. CONCLUSION: Cx43KO embryonic mice exhibit delayed myocardialization. As compared with the Cx43(+/+), the expression of Bmpr2 in proximal OFT septum was delayed obviously in Cx43(+/-) and Cx43(-/-) mice. And the expression of Bmpr2 is abnormal in OFT septum of Cx43(+/-) and Cx43(-/-) fetal heart. Bmpr2 may be involved in the interaction between epicardium and myocardium. It may be a critical mechanism in the maturation process of cardiac muscles. PMID- 22094043 TI - [Autophagy of human vascular endothelial cells by oxidized low-density lipoprotein: involvement of oxidative stress but no oxidized low density lipoprotein-1]. AB - OBJECTIVE: Our previous studies found that 100 ug/ml oxidized low-density lipoprotein (ox-LDL) could up-regulate the autophagic level in human umbilical vein endothelial cells (HUVEC). The present study was conducted to observe the roles of oxidative stress and lectin-like oxidized low density lipoprotein-1 (LOX 1) in the ox-LDL-induced up-regulation of autophagy. METHODS: Prior to the ox-LDL exposure, LOX-1mAb, vitamin C and vitamin E were used to study the roles of LOX-1 and oxidative stress in the activation of autophagy. The contents of total superoxide dismutase (T-SOD) and MDA (malondialdehyde) in the culture medium were detected with enzyme linked immunosorbent assay. Western blot was employed to detect the levels of autophagic marker microtubule-associated protein light chain 3 (MAP1-LC3)-II/LC3-I, beclin1 and lysosome associated membrane protein 2a (lamp2a). RESULTS: After the ox-LDL exposure, the down-regulated level of T-SOD [0.5 h (32.73 +/- 1.09 vs 40.16 +/- 1.28) U/ml, P < 0.01; 6 h (29.32 +/- 1.56 vs 40.16 +/- 1.28) U/ml, P < 0.01] and the up-regulated level of MDA [0.5 h (1.11 +/ 0.04 vs 0.57 +/- 0.05) nmol/ml, P < 0.01; 6 h (0.69 +/- 0.03 vs 0.57 +/- 0.05) nmol/ml, P < 0.05] in culture medium were also significant at 0.5 h and 6 h. The ox-LDL-induced increased ratio of LC3-II/LC3-I was reversed by the pretreatments of vitamin C and vitamin E (0.5 h, vitC: 3.11 +/- 0.02 vs 4.31 +/- 0.50, P < 0.05; vitE: 3.46 +/- 0.19 vs 4.31 +/- 0.50, P < 0.05; 6 h, vitC: 1.44 +/- 0.05 vs 2.31 +/- 0.16, P < 0.05), but not LOX-1mAb. LOX-1mAb decreased the ox-LDL-induced elevated level of lamp2a protein while vitamin C and vitamin E only inhibited the elevation of lamp2a at the timepoint of 6 h, but not 0.5 h. CONCLUSION: Oxidative stress, rather than LOX-1, plays an important role in the ox-LDL-induced up regulation of autophagy in HUVEC. The formation of autolysosomes is associated with the LOX-1-mediated endocytosis of ox-LDL. Oxidative stress only plays a minor role in the formation of autolysosomes induced by the engulfed ox-LDL. PMID- 22094044 TI - Conceptualization of category-oriented likelihood ratio: a useful tool for clinical diagnostic reasoning. AB - BACKGROUND: In the diagnostic reasoning process medical students and novice physicians need to be made aware of the diagnostic values of the clinical findings (including history, signs, and symptoms) to make an appropriate diagnostic decision. Diagnostic reasoning has been understood in light of two paradigms on clinical reasoning: problem solving and decision making. They advocate the reasoning strategies used by expert physicians and the statistical models of reasoning, respectively. Evidence-based medicine (EBM) applies decision theory to the clinical diagnosis, which can be a challenging topic in medical education.This theoretical article tries to compare evidence-based diagnosis with expert-based strategies in clinical diagnosis and also defines a novel concept of category-oriented likelihood ratio (LR) to propose a new model combining both aforementioned methods. DISCUSSION: Evidence-based medicine advocates the use of quantitative evidence to estimate the probability of diseases more accurately and objectively; however, the published evidence for a given diagnosis cannot practically be utilized in primary care, especially if the patient is complaining of a nonspecific problem such as abdominal pain that could have a long list of differential diagnoses. In this case, expert physicians examine the key clinical findings that could differentiate between broader categories of diseases such as organic and non-organic disease categories to shorten the list of differential diagnoses. To approach nonspecific problems, not only do the experts revise the probability estimate of specific diseases, but also they revise the probability estimate of the categories of diseases by using the available clinical findings. SUMMARY: To make this approach analytical and objective, we need to know how much more likely it is for a key clinical finding to be present in patients with one of the diseases of a specific category versus those with a disease not included in that category. In this paper, we call this value category-oriented LR. PMID- 22094045 TI - Alpha spindles as neurophysiological correlates indicating attentional shift in a simulated driving task. AB - The intention of this paper is to describe neurophysiological correlates of driver distraction with highly robust parameters in the EEG (i.e. alpha spindles). In a simulated driving task with two different secondary tasks (i.e. visuomotor, auditory), N=28 participants had to perform full stop brakes reacting to appearing stop signs and red traffic lights. Alpha spindle rate was significantly higher during an auditory secondary task and significantly lower during a visuomotor secondary task as compared to driving only. Alpha spindle duration was significantly shortened during a visuomotor secondary task. The results are consistent with the assumption that alpha spindles indicate active inhibition of visual information processing. Effects on the alpha spindles while performing secondary tasks on top of the driving task indicate attentional shift according to the task modality. As compared to alpha band power, both the measures of alpha spindle rate and alpha spindle duration were less vulnerable to artifacts and the effect sizes were larger, allowing for a more accurate description of the current driver state. PMID- 22094048 TI - Neutrophils in tuberculosis: friend or foe? AB - Neutrophils are rapidly recruited to sites of mycobacterial infection, where they phagocytose bacilli. Whether neutrophils can kill mycobacteria in vivo probably depends on the tissue microenvironment, stage of infection, individual host, and infecting organism. The interaction of neutrophils with macrophages, as well as the downstream effects on T cell activity, could result in a range of outcomes from early clearance of infection to dissemination of viable bacteria together with an attenuated acquired immune response. In established disease, neutrophils accumulate in situations of high pathogen load or immunological dysfunction, and are likely to contribute to pathology. These activities may have clinical importance in terms of new treatments, targeted interventions and vaccine strategies. PMID- 22094047 TI - The effect of fast-food availability on fast-food consumption and obesity among rural residents: an analysis by race/ethnicity. AB - Rural areas of the United States tend to have higher obesity rates than urban areas, particularly in regions with high proportions of non-white residents. This paper analyzes the effect of fast-food availability on the level of fast-food consumption and obesity risk among both white and non-white residents of central Texas. Potential endogeneity of fast-food availability is addressed through instrumental variables regression using distance to the nearest major highway as an instrument. We find that non-whites tend to exhibit higher obesity rates, greater access to fast-food establishments and higher consumption of fast-food meals compared to their white counterparts. In addition, we found that whites and non-whites respond differently to the availability of fast-food in rural environments. Greater availability is not associated with either greater consumption of fast-food meals or a higher obesity risk among the sample of whites. In contrast, greater availability of fast-food is positively associated with both the number of meals consumed for non-white rural residents and their obesity. While our results are robust to specification, the effect of availability on weight outcomes is notably weaker when indirectly calculated from the implied relationship between consumption and caloric intake. This highlights the importance of directly examining the proposed mechanism through which an environmental factor influences weight outcomes. PMID- 22094046 TI - Effects of abiotic stress on plants: a systems biology perspective. AB - The natural environment for plants is composed of a complex set of abiotic stresses and biotic stresses. Plant responses to these stresses are equally complex. Systems biology approaches facilitate a multi-targeted approach by allowing one to identify regulatory hubs in complex networks. Systems biology takes the molecular parts (transcripts, proteins and metabolites) of an organism and attempts to fit them into functional networks or models designed to describe and predict the dynamic activities of that organism in different environments. In this review, research progress in plant responses to abiotic stresses is summarized from the physiological level to the molecular level. New insights obtained from the integration of omics datasets are highlighted. Gaps in our knowledge are identified, providing additional focus areas for crop improvement research in the future. PMID- 22094049 TI - Metal contamination of short-term snow cover near urban crossroads: correlation analysis of metal content and fine particles distribution. AB - Snow samples were collected near crossroads in Novi Sad, Serbia, during December 2009 to assess metal concentrations (Ca, K, Zn, Fe, Cu, Mn, Al, Pb and Na), fine particle distribution and pH value. The filtered samples of melted snow were analysed, with a focus on particles smaller than a few MUm. The most common values of the frequency number distribution curve were either in the range of 0.05-0.07 MUm or one order of magnitude higher (0.2-0.5 MUm). At examined locations metal concentrations varied from 0.0004 mg L(-1) for Pb to 18.9 mg L( 1) for Na. Besides Na, which mostly originated from de-icing salt, Ca is found to be the most abundant element in snow indicating the dominant influence of natural factors on snow chemistry. No significant difference was found in concentration of the elements at locations near crossroads with either low or high traffic volume, except for Na and Zn. To investigate how metals were related a correlation analysis was done for the concentrations of metals and with respect to the particle size distribution parameters and pH values. The major influence on the fine particle volume (mass) was concluded to be due to the elements from anthropogenic sources. This conclusion was based on the significant positive correlation between Fe, Zn and Al and the fine particle volume based distribution parameters. PMID- 22094050 TI - Reduction of U(VI) by the deep subsurface bacterium, Thermus scotoductus SA-01, and the involvement of the ABC transporter protein. AB - In this study we investigated the effect of uranium on the growth of the bacterium Thermus scotoductus strain SA-01 as well as the whole cell U(VI) reduction capabilities of the organism. Also, site-directed mutagenesis confirmed the identity of a protein capable of a possible alternative mechanism of U(VI) reduction. SA-01 can grow aerobically in up to 1.25 mM uranium and has the capability to reduce low levels of U(VI) in under 20 h. TEM analysis performed on cells exposed to uranium showed extracellular and membrane-bound accumulation of uranium. The reductase-like protein was surprisingly identified as a peptide ABC transporter, peptide-binding protein. This study showcases the concept of protein promiscuity, where this protein with a distinct function in situ can also have the unintended function of a reactant for the reduction of U(VI). PMID- 22094051 TI - Anaerobic degradation of microcrystalline cellulose: kinetics and micro-scale structure evolution. AB - The degradation kinetics and micro-scale structure change of microcrystalline cellulose during anaerobic biodegradation were investigated. A modified Logistic model was established to properly describe the kinetics, which showed good fitness and wide applicability for cellulose degradation. A maximum degradation rate of 0.14 g L(-1) h(-1) was achieved after cultivating for 51.5 h. This result was in good agreement with the scanning electron microscope and X-ray diffraction analysis. Channels of 400-500 nm size started to occur on the crystalline surface of cellulose at around the inflexion time. Accordingly, the crystallinity significantly decreased at this point, indicating a degradation of the crystalline structure zones by anaerobic bacteria. This study offers direct morphological evidence and quantitative analysis of the biodegradation process of cellulose, and is beneficial to a better understanding of the cellulose degradation mechanism. PMID- 22094052 TI - Partitioning of arsenic in soil-crop systems irrigated using groundwater: a case study of rice paddy soils in southwestern Taiwan. AB - The accumulation of As in rice due to groundwater irrigation in paddy fields represents a serious health hazard in South and Southeast Asia. In Taiwan, the fate of As in long-term irrigated paddy fields is poorly understood. Groundwater, surface soil, and rice samples were collected from a paddy field that was irrigated with As-containing groundwater in southwestern Taiwan. The purpose of this study is to elucidate the source and sink of As in the paddy field by comparing the As fractions in the soils that were obtained by a sequential extraction procedure (SEP) with the As uptake of rice. The risks associated with eating rice from the field can thus be better understood. The concentration of As in groundwater varied with time throughout the growing seasons of rice, but always exceeded the permitted maximum (10 MUg L(-1)) for drinking water by the WHO. The As concentration increased with the concentration of Fe in the groundwater, supporting the claim that a large amount of As was concentrated in the Fe flocs collected from the internal wall of the groundwater pump. The results of the SEP revealed that As bound with amorphous and crystalline hydrous oxides exhibited high availability in the soils. The root of rice accumulated the largest amount of As, followed by the straw, husk, and grain. Although the As concentration in the rice grain was less than 1.0 mg kg(-1), the estimated intake level was close to the maximum tolerable daily intake of As, as specified by the WHO. PMID- 22094053 TI - Experimental evaluation of PCDD/Fs and PCBs release and mass balance of a WTE plant. AB - The behaviour of waste incineration plants with respect to organic toxic trace contaminants such as PCDDs, PCDFs and, to a minor extent, PCBs, is still a matter of concern for the public opinion and the decision makers. It is therefore very important, first, to evaluate the release of these organic toxic trace contaminants in the environment during waste incineration, not only through the stack gas emission but also with the solid and liquid residues, and then to compare the total release with the input through the treated waste in order to assess the plant behaviour as a "sink" rather than a "source" of organic toxic trace contaminants. The experimental investigation carried out on an Italian full scale incineration plant has shown a total 17 PCDD/Fs and 12 dioxin-like PCBs release of 5.5-27 MUg WHO-TEQ per tonne of treated waste and an input flux of 1.6 44 MUg WHO-TEQ per tonne of waste, with the difference between the input and the output fluxes rather small and the plant behaviour toward organic trace toxic contaminants in average neutral. Results are compared with similar evaluations conducted in the last decade on a number of waste-to-energy (WTE) plants operating in Italy. PMID- 22094054 TI - The culturable intestinal microbiota of triploid and diploid juvenile Atlantic salmon (Salmo salar) - a comparison of composition and drug resistance. AB - BACKGROUND: With the increased use of ploidy manipulation in aquaculture and fisheries management this investigation aimed to determine whether triploidy influences culturable intestinal microbiota composition and bacterial drug resistance in Atlantic salmon (Salmo salar). The results could provide answers to some of the physiological differences observed between triploid and diploid fish, especially in terms of fish health. RESULTS: No ploidy effect was observed in the bacterial species isolated, however, triploids were found to contain a significant increase in total gut microbiota levels, with increases in Pseudomonas spp., Pectobacterium carotovorum, Psychrobacter spp., Bacillus spp., and Vibrio spp., (12, 42, 9, 10, and 11% more bacteria in triploids than diploids, respectively), whereas a decrease in Carnobacterium spp., within triploids compared to diploids was close to significant (8% more bacteria in diploids). With the exception of gentamicin, where no bacterial resistance was observed, bacterial isolates originating from triploid hosts displayed increased resistance to antibacterials, three of which were significant (tetracycline, trimethoprim, and sulphonamide). CONCLUSION: Results indicate that triploidy influences both the community and drug resistance of culturable intestinal microbiota in juvenile salmon. These results demonstrate differences that are likely to contribute to the health of triploid fish and have important ramifications on the use of antibacterial drugs within aquaculture. PMID- 22094055 TI - Comparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in rat. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Escin Ia and isoescin Ia have been traditionally used clinically as the chief active ingredients of escin, a major triterpene saponin isolated from horse chestnut (Aesculus hippocastanum) seeds for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema. AIM OF THE STUDY: To establish a sensitive LC-MS/MS method and investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetics difference of sodium escinate with pure escin Ia and isoescin Ia. The absolute bioavailability of escin Ia and isoescin Ia and the bidirectional interconversion of them in vivo were also scarcely reported. MATERIALS AND METHODS: Wister rats were administrated an intravenous (i.v.) dose (1.7 mg/kg) of sodium escinate (corresponding to 0.5mg/kg of escin Ia and 0.5mg/kg of isoescin Ia, respectively) and an i.v. dose (0.5mg/kg) or oral dose (4mg/kg) of pure escin Ia or isoescin Ia, respectively. At different time points, the concentrations of escin Ia and isoescin Ia in rat plasma were determined by LC-MS/MS method. Main pharmacokinetic parameters including t(1/2), MRT, CL, V(d), AUC and F were estimated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany) and statistical analysis was performed using the Student's t-test with P<0.05 as the level of significance. RESULTS: After administration of sodium escinate, the t(1/2) and MRT values for both escin Ia and isoescin Ia were larger than corresponding values for the compounds given alone. Absorption of escin Ia and isoescin Ia was very low with F values both <0.25%. Escin Ia and isoescin Ia were found to form the other isomer in vivo with the conversion of escin Ia to isoescin Ia being much extensive than from isoescin Ia to escin Ia. CONCLUSION: Comparison of the pharmacokinetics of escin Ia and isoescin Ia given alone and together in rat suggest that administration of herbal preparations of escin for clinical use may provide longer duration of action than administration of single isomers. The interconversion of escin Ia and isoescin Ia when given alone indicates that administration of one isomer leads to exposure to the other. PMID- 22094057 TI - Diverse interactions mediate asymmetric incompatibility by the het-6 supergene complex in Neurospora crassa. AB - Heterokaryon incompatibility (HI) in filamentous fungi is a form of nonself recognition that operates during the vegetative phase of the life cycle. One HI gene complex in Neurospora crassa, the het-6 locus, comprises two incompatibility genes, het-6 and un-24, each having two allelic variants, Oak Ridge (OR) and Panama (PA). The un-24 gene also encodes the large subunit of ribonucleotide reductase while het-6 appears to be a member of a repetitive gene family with no other known function aside from HI. These two genes are in severe linkage disequilibrium such that only un-24(OR)het-6(OR) and un-24(PA)het-6(PA) haplotypes occur in nature. In this study we unravel several genetic interactions that govern the HI functions of this gene complex. We use novel un-24(PA)het 6(OR) strains and het-6 deletion strains to demonstrate that nonallelic interactions occur between un-24 and het-6 and reveal an allelic incompatibility interaction between the OR and PA forms of un-24 that is asymmetrically enhanced by the presence of het-6(OR) or het-6(PA). We also show how two allelic forms of vib-1, a suppressor of het-c- and mat-associated incompatibility, differentially act as recessive suppressors of HI associated with nonallelic interactions between un-24(PA) and het-6(OR). In contrast, vib-1 is a dominant suppressor of HI associated with allelic differences at un-24 and a dominant partial suppressor of the un-24(OR) and het-6(PA) nonallelic interaction. The range of suppressor activities is largely explained by an interesting differential effect on het 6(OR) and het-6(PA) transcript levels by VIB-1. PMID- 22094056 TI - Analgesic and anti-inflammatory activity and pharmacokinetics of alkaloids from seeds of Strychnos nux-vomica after transdermal administration: effect of changes in alkaloid composition. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Strychnos nux-vomica L. (Loganiaceae) is grown extensively in southern Asian countries. The dried seed of this plant, nux vomica, has been clinically used in Chinese folk medicine for improving blood circulation, relieving rheumatic pain, reducing swelling and treating cancer. AIM OF THE STUDY: This study was carried out to investigate the effect of removing most strychnine from the total alkaloid fraction (TAF) extracted from nux vomica on analgesic and anti-inflammatory activity and pharmacokinetics after transdermal administration. MATERIALS AND METHODS: Most strychnine was removed from TAF and the resulted modified total alkaloid fraction (MTAF) was obtained. The contents of strychnine and brucine in TAF and MTAF were determined. Then the analgesic and anti-inflammatory activity of TAF, MTAF, brucine and strychnine dissolved in hydrogel was compared after transdermal administration. Furthermore, in vitro and in vivo transdermal absorption profiles of brucine after administration of TAF, MTAF and brucine dissolved in hydrogel were also compared. RESULTS: In contrast to TAF, most strychnine was removed from MTAF and the ratio of brucine to strychnine was adjusted from 1:1.8 to 2.7:1. MTAF showed significant analgesic activity in all the chemical-, thermal- and physical- induced nociception models, which indicated the presence of both centrally and peripherally mediated activities. MTAF also showed significant anti-inflammatory activity against xylene-induced ear edema. But TAF and strychnine demonstrated little activity in all those pharmacological tests. Brucine showed to be effective in acetic acid-induced writhing and xylene-induced ear edema test. Brucine in MTAF was absorbed more completely than it alone at the same dosage of brucine after transdermal administration. CONCLUSIONS: The results from the present study appeared to support the viewpoint that most strychnine should be removed from TAF to improve analgesic and anti-inflammatory activity. The relatively higher pharmacological activity of MTAF compared to brucine alone is partly due to the enhanced transdermal absorption of brucine. PMID- 22094058 TI - Alternative splicing directs dual localization of Candida albicans 6 phosphogluconate dehydrogenase to cytosol and peroxisomes. AB - The pentose phosphate pathway (PPP) is the main source of NADPH in the cell and therefore essential for the maintenance of the redox balance and anabolic reactions. NADPH is produced by the two dehydrogenases in the oxidative branch of the PPP: glucose-6-phosphate dehydrogenase (Zwf1) and 6-phosphogluconate dehydrogenase (Gnd1). We observed that in the commensal fungus Candida albicans these two enzymes contain putative peroxisomal targeting signals (PTSs): Zwf1 has a putative PTS1, while the annotated intron of GND1 encodes a PTS2. By subcellular fractionation and fluorescence microscopy, we show that both enzymes have a dual localization in which the majority is cytosolic, but a small fraction is peroxisome associated. Analysis of GND1 transcripts revealed that dual targeting of Gnd1 is directed by alternative splicing resulting in two Gnd1 isoforms, one without targeting signals localized to the cytosol and one with an N-terminal PTS2 targeted to peroxisomes. To our knowledge, Gnd1 is the first example of dual targeting of a protein by alternative splicing in C. albicans. In silico analysis suggests that PTS-mediated peroxisomal targeting of Zwf1 and Gnd1 is conserved across closely related Candida species. We discuss putative functions of the peroxisomal oxidative PPP in these organisms. PMID- 22094059 TI - The phantom spider and other myths. PMID- 22094060 TI - Hydrophobic statins induce autophagy and cell death in human rhabdomyosarcoma cells by depleting geranylgeranyl diphosphate. AB - Statins are the most common type of medicine used to treat hypercholesterolemia; however, they are associated with a low incidence of myotoxicity such as myopathy and rhabdomyolysis. The mechanisms for the adverse effects remain to be fully elucidated for safer chronic use and drug development. The results of our earlier work suggested that hydrophobic statins induce autophagy in cultured human rhabdomyosarcoma A204 cells. In this study, we first confirmed the statin-induced autophagy by assessing other criteria, including induced expression of the autophagy-related genes, enhanced protein degradation of autophagy marker protein p62 and electron microscopic observation of induced formation of autophagosome. We next demonstrated that the extent of inhibition of HMG-CoA reductase in the cell is parallel with the ability of a statin to induce autophagy. Thus, the primary activity of statins causes autophagy in A204 cells. Considering the mechanism for the induction, we showed that statins induce autophagy by depleting cellular levels of geranylgeranyl diphosphate (GGPP) mostly through an unknown pathway that does not involve two major small G proteins, Rheb and Ras. Finally, we demonstrated that the ability of statins to induce autophagy parallels their toxicity to A204 cells and that both can be suppressed by GGPP. PMID- 22094061 TI - The role of extracellular-signal regulate kinase (ERK) in the regulation of airway tone in porcine isolated peripheral bronchioles. AB - Extracellular signal regulated kinase (ERK) is known to regulate vascular smooth muscle contraction. However, a role for ERK in airway smooth muscle contraction has yet to be demonstrated conclusively, although contractile agents increase ERK activity in airway smooth muscle. Rather than initiating contraction, ERK could regulate airway tone by interfering with relaxation. Therefore, the aim of this study was to determine whether ERK regulates contraction or relaxation of airway smooth muscle. Segments of porcine peripheral bronchioles were mounted in an isolated tissue bath in Krebs-Henseleit buffer and maintained at 37 degrees C. Cumulative concentration-response curves to histamine, endothelin-1, or the muscarinic agonist carbachol were then carried out in the absence or presence of the MEK inhibitor PD98059. In separate experiments, cumulative concentration response curves to the beta-adrenoceptor agonist isoprenaline or the adenylyl cyclase activator forskolin were carried out in the absence or presence of the MEK inhibitors PD98059 or U0126. ERK activity was measured by Western blotting. All three contractile agents increased ERK activity, but the contractile responses were unaffected by PD98059. On the other hand, both PD98059 and U0126 enhanced the relaxations to isoprenaline but not relaxations to the adenylyl cyclase activator forskolin. The enhancement of isoprenaline-induced relaxations with PD98059 was prevented by the K(+) channel blocker tetraethylammonium. These data suggest that ERK regulates airway smooth muscle tone by inhibiting beta adrenoceptor-mediated relaxations, rather than an initiation of contraction. The effect on beta-adrenoceptor-mediated responses appears to be through a cAMP independent mechanism, possibly through an interaction with K(+) channels. PMID- 22094062 TI - Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast induced nephropathy in the diabetic rats: a comparison with n-acetylcysteine. AB - The aim of this study was to investigate the effects of apocynin, a NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase inhibitor, in diabetic rats with nephropathy induced by contrast medium (CIN). Diabetes was induced in male Wistar rats by a single dose of streptozotocin (60 mg/kg i.v.). Animals were then divided into the following groups: 1) control group (diabetic rats treated i.v. with saline solution); 2) iomeprol group (iomeprol at 10 ml/kg was injected i.v. 30 min after saline administration); 3) apocynin group (identical to the iomeprol group, except for pre-treatment with apocynin 5mg/kg i.v., 30 min before iomeprol injection) and 4) N-acetylcysteine group (NAC) (same as iomeprol group, except for the treatment with NAC 20 mg/kg i.v. 30 min before iomeprol injection). CIN in animals were assessed 24h after administration of iomeprol. Apocynin significantly attenuates the impaired glomerular function, concentration of Na(+), K(+), alpha glutathione S-transferase levels in urine and neutrophil gelatinase-associated lipocalin levels in plasma caused by iomeprol. In kidney, immunohistochemical analysis of some inflammatory mediators, such as nitrotyrosine, poly-ADP-ribosyl polymerase, tumor necrosis factor-alpha, interleukin-1beta as well as apoptosis (evaluated as terminal deoxynucleotidyltransferase-mediated UTP end labeling assay) revealed positive staining in tissue obtained from iomeprol group. These parameters were markedly reduced in animals treated with apocynin. Similarly, these parameters were also markedly modified by NAC pre-treatment. Here, we have shown that apocynin attenuates the degree of iomeprol-induced nephropathy in diabetic rats. PMID- 22094063 TI - Differential vasoactive effects of sildenafil and tadalafil on cerebral arteries. AB - Phosphodiesterase 5 (PDE5) is associated with migraine pathophysiology, stroke recovery and vasospasm treatment. The potential vascular interplay of PDE5 inhibitors sildenafil, tadalafil and UK-114,542 was studied by intra- versus extra-luminal administration in rat middle cerebral arteries in vitro and on middle meningeal arteries in vivo. By Western blot PDE5 was detected in both cerebral and meningeal arteries, though with minor variations in band intensity between vascular beds. Rat middle cerebral artery diameter was investigated using pressurised arteriography, applying UK-114,542, sildenafil, and tadalafil intra- or extra-luminally. Effects on the dural middle meningeal artery were studied in the in vivo closed cranial window model. At high concentrations, abluminal sildenafil and UK-114,542, but not tadalafil, induced dilatation of the middle cerebral artery. Luminal application elicited a contraction of 4% (sildenafil, P=0.03) and 10% (tadalafil, P=0.02). In vivo, sildenafil, but not tadalafil, dose dependently dilated middle meningeal artery concomitant to blood pressure reduction (1-3mg/kg);1mg/kg sildenafil inducing 60 +/- 14% (P=0.04) and vehicle (DMSO) 13 +/- 6% dilatation. In conclusion, PDE5 inhibitors applied luminally had minor contractile effect, whereas abluminal sildenafil induced middle cerebral artery dilatation above therapeutic levels. In vivo, sildenafil dilated middle meningeal artery concomitant with a reduction in blood pressure. Tadalafil had no dilatory effects. PDE5 inhibitors show differential vascular activity in cerebral arteries from healthy animals; arterial dilatation is seen primarily above therapeutic levels. Such findings support clinical studies showing no vasodilator effects of sildenafil on cerebral arteries in healthy subjects. PMID- 22094064 TI - Effect of iridoid glucoside on streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolic enzymes. AB - Vitex negundo is a medicinal plant used to treat many ailments. An active compound of iridoid glucoside was isolated from V. negundo leaves and its efficacy was investigated in streptozotocin induced diabetic rats with special reference to carbohydrate metabolizing enzymes. The optimum dose of iridoid glucoside was determined by oral glucose tolerance test. The effects of iridoid glucoside were compared with glibenclamide Administration of iridoid glucoside (50mg/kg body weight) to diabetic rats for 30 days resulted in significant reduction in the levels of plasma glucose, glycosylated hemoglobin and increase in the levels of insulin and hemoglobin. Administration of iridoid glucoside showed a significant increase in the levels of glycolytic enzymes and glycogen content and decrease in the levels of gluconeogenic enzymes in the liver of diabetic treated rats. Further, iridoid glucoside showed antihyperlipidemic activity as evidenced by significant reduction in serum total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein coupled together with elevation of high density lipoprotein in diabetic rats. A significant decrease was observed in the activities of aspartate aminotransferase, alanine aminotransferase and decrease in the levels of serum urea and creatinine in diabetic treated rats when compared to diabetic untreated rats. Treatment of iridoid glucoside alleviated body weight loss in diabetic rats. The effect produced by iridoid glucoside on various parameters was comparable to that of glibenclamide. These results indicate that iridoid glucoside possess antihyperlipidemic effect in addition to its antidiabetic effect. PMID- 22094065 TI - The noble gas argon modifies extracellular signal-regulated kinase 1/2 signaling in neurons and glial cells. AB - Recently, the noble gas argon has been identified as a potent neuroprotective agent, but little is known about its cellular effects. In this in vitro study, we investigated argon's influence on the extracellular signal-regulated kinase (ERK) 1/2, a ubiquitous enzyme with numerous functions in cell proliferation and survival. Primary neuronal and astroglial cell cultures and the microglial cell line BV-2 were exposed to 50 vol.% argon. Further possible effects were studied following stimulation of microglia with 50 ng/ml LPS. ERK 1/2 activation was assessed by phosphorylation state-specific western blotting, cytokine levels by real-time PCR and western blotting. Total phosphotyrosine phosphatase activity was examined with p-nitrophenylphosphate. After 30 min exposure, argon significantly activated ERK 1/2 signaling in microglia. Enhanced phosphorylation of ERK 1/2 was also found in astrocytes and neurons following argon exposure, but it lacked statistical significance. In microglia, argon did not substantially interfere with LPS-induced ERK1/2 activation and inflammatory cytokine induction. Addition of the MEK-Inhibitor U0126 abolished the induced ERK 1/2 phosphorylation. Cellular phosphatase activity and the inactivation of phosphorylated ERK 1/2 were not altered by argon. In conclusion, argon enhanced ERK 1/2 activity in microglia via the upstream kinase MEK, probably through a direct mode of activation. ERK 1/2 signaling in astrocytes and neurons in vitro was also influenced, although not with statistical significance. Whether ERK 1/2 activation by argon affects cellular functions like differentiation and survival in the brain in vivo will have to be determined in future experiments. PMID- 22094066 TI - A synthetic prostacyclin agonist with thromboxane synthase inhibitory activity, ONO-1301, protects myocardium from ischemia/reperfusion injury. AB - ONO-1301, a synthetic prostacyclin agonist with thromboxane synthase inhibitory activity, promotes the production of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) by various cell types. Here, we evaluated the therapeutic efficacy of ONO-1301 in rats with ischemia/reperfusion injury. Ligation of the left anterior descending arteries was performed in 10-week-old Wistar rats, and released 30 min later. A slow-release form of ONO-1301 was administered subcutaneously at 3h and 3 weeks after reperfusion injury. Hemodynamic parameters were significantly improved in the ONO-1301 group. Histological analysis revealed that ONO-1301 suppressed ischemic and fibrotic changes in the myocardium (ischemic area, control group: 58.6 +/- 8.7% vs. ONO 1301 group: 44.4 +/- 5.8%, fibrotic area, 33.5 +/- 5.9% vs. 22.3 +/- 6.2%, P<0.05, respectively), and enhanced neovascularization in the border zone. HGF expression was up-regulated by ONO-1301. Double-immunostaining revealed that myofibroblasts in the border zone of ischemic myocardium mainly expressed HGF. Our findings suggest that ONO-1301 might have therapeutic potential in treating ischemic heart disease. PMID- 22094067 TI - Protective effects of ligustrazine on TNF-alpha-induced endothelial dysfunction. AB - To investigate the effects of Ligustrazine, a compound derived from chuanxiong, on tumor necrosis factor-alpha (TNF-alpha) stimulated endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-alpha in vitro. Nitric oxide (NO) was measured as a standard of endothelial dysfunction. Two important indicators of autoimmunity, intracellular adhesion molecular-1 (ICAM-1) and heat shock protein 60 (HSP60), were selected to evaluate the influence of Ligustrazine on HUVECs. Ligustrazine (40 MUg/ml) significantly reversed the decrease in NO production induced by TNF-alpha (5 ng/ml) in HUVECs. The expressions of ICAM-1 and HSP60 were increased by TNF-alpha treatment, but dramatically inhibited by treatment with ligustrazine in TNF-alpha-stimulated cells. Ligustrazine increased the production of NO in HUVECs and had an immunomodulatory effect on HUVECs stimulated with TNF-alpha by down-regulating the expression of ICAM-1 and HSP60. These results suggest that ligustrazine protects the endothelium via inhibition of immunological reactions, preventing atherosclerosis. PMID- 22094068 TI - Functional antagonism of amphetamine versus ethanol on adrenergic neurotransmission in vas deferens of adolescent rats. AB - Because of the few studies that emphasize the in vivo use of amphetamine and ethanol, and their consequences on autonomic neurotransmission, we decided to study the effect of these drugs on peripheral noradrenergic neurotransmission of young animals. We used contractions of the vas deferens of adolescent rats as a model for the study of pre-treatment with both agents. The 30 to 40 day old adolescent rats were pre-treated with amphetamine, at doses of 3mg/kg, or ethanol at doses of 1.2 g/kg. Both agents were also used simultaneously to investigate possible interactions. The group treated with amphetamine showed a potentiation of the vas deferens contractions evoked by noradrenaline and barium (about 20%), as well as time-response contractions of calcium (about 20%). However, the response to electrical field stimulation (EFS) was not significantly changed, but the content of noradrenaline was reduced by about 50%. The group treated with ethanol showed a decrease in vas deferens contractility to noradrenaline, phenylephrine, and barium, by less than 20%. In this group, contraction by EFS was reduced by about 40% (Tonic, 2 Hz) and 20% (Phasic, 5 Hz), but the response to calcium was not changed. As after amphetamine, the content of noradrenaline was reduced by about 50%. In the group treated with amphetamine+ethanol all the changes described after the single treatments with amphetamine or ethanol were neutralized. It is concluded that a functional antagonism was shown between amphetamine and ethanol when administered simultaneously on peripheral sympathetic neurotransmission in vas deferens of adolescent animals. PMID- 22094069 TI - Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene. AB - Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle. We have studied 48 families with myotonia, 32 out of them carrying mutations in CLCN1 gene and eight carry mutations in SCN4A gene. We have found 26 different mutations in CLCN1 gene, including 13 not reported previously. Among those 26 mutations, c.180+3A>T in intron 1 is present in nearly one half of the Spanish families in this series, the largest one analyzed in Spain so far. Although scarce data have been published on the frequency of mutation c.180+3A>T in other populations, our data suggest that this mutation is more frequent in Spain than in other European populations. In addition, expression in HEK293 cells of the new missense mutants Tyr137Asp, Gly230Val, Gly233Val, Tyr302His, Gly416Glu, Arg421Cys, Asn567Lys and Gln788Pro, demonstrated that these DNA variants are disease-causing mutations that abrogate chloride currents. PMID- 22094070 TI - [The Sertoli cell]. AB - The Sertoli cell is essential for the formation and functioning of the testis. This is the first cell to differentiate into the initially bipotential genital ridge and is the only somatic cell present in seminiferous tubules. Maturation involves the loss of proliferative capacity, formation of intercellular tight junctions and the appearance of some specific markers. We can consider schematically two distinct roles associated with different features: a process of sexual differentiation with testicular formation and a role in spermatogenesis allowing the germ cells progression into sperm through close contact in the seminiferous tubules. These events, separated in time, are in fact intimately linked. PMID- 22094071 TI - Impulsive action and impulsive choice are mediated by distinct neuropharmacological substrates in rat. AB - Impulsivity is a heterogeneous construct according to clinical and preclinical behavioural measures and there is some preliminary evidence indicating distinct neurobiological substrates underlying the sub-components of impulsivity. Two preclinical assays, the five-choice serial reaction time task (5-CSRTT) and the delayed discounting task (DDT), are hypothesized to provide measures of impulsive action (premature responding) and impulsive choice (percent choice for delayed reward), respectively. In the present studies, we show that the norepinephrine reuptake inhibitor atomoxetine attenuated premature responding in the 5-CSRTT, but was ineffective in the DDT. The mixed dopamine/norepinephrine reuptake inhibitor methylphenidate exhibited an opposite profile of effects. In addition, blockade of 5-HT2A/C receptors via ketanserin decreased premature responding but had no effects on percent choice for delayed reward; blockade of 5-HT2C receptors via SB 242084 had opposite effects. Follow-up studies provided some limited evidence of additive effects of 5-HT2A/C receptor blockade on the effects of atomoxetine on impulsive action. These studies demonstrate dissociable profiles of stimulant vs. non-stimulant attention deficit hyperactivity disorder medications and 5-HT subtype-selective ligands, in the 5-CSRTT and DDT assays. Thus, the present findings support the sub-categorization of impulsivity and suggest that 5-HT receptor subtype-selective antagonists may provide therapeutic targets for disorders characterized by different forms of impulsivity. PMID- 22094072 TI - The prognostic value of early repolarization with ST-segment elevation in African Americans. AB - BACKGROUND: Increased prevalence of classic early repolarization, defined as ST segment elevation (STE) in the absence of acute myocardial injury, in African Americans is well established. The prognostic value of this pattern in different ethnicities remains controversial. OBJECTIVE: Measure association between early repolarization and cardiovascular mortality in African Americans. METHODS: The resting electrocardiograms of 45,829 patients were evaluated at the Palo Alto Veterans Affairs Hospital. Subjects with inpatient status or electrocardiographic evidence of acute myocardial infarction were excluded, leaving 29,281 subjects. ST-segment elevation, defined as an elevation of >0.1 mV at the end of the QRS, was electronically flagged and visually adjudicated by 3 observers blinded to outcomes. An association between ethnicity and early repolarization was measured by using multivariate logistic regression. We analyzed associations between early repolarization and cardiovascular mortality by using the Cox proportional hazards regression analysis. RESULTS: Subjects were 13% women and 13.3% African Americans, with an average age of 55 years and followed for an average of 7.6 years, resulting in 1995 cardiovascular deaths. There were 479 subjects with lateral STE and 185 with inferior STE. After adjustment for age, sex, heart rate, and coronary artery disease, African American ethnicity was associated with lateral or inferior STE (odds ratio 3.1; P = .0001). While lateral or inferior STE in non-African Americans was independently associated with cardiovascular death (hazard ratio 1.6; P = .02), it was not associated with cardiovascular death in African Americans (hazard ratio 0.75; P = .50). CONCLUSIONS: Although early repolarization is more prevalent in African Americans, it is not predictive of cardiovascular death in this population and may represent a distinct electrophysiologic phenomenon. PMID- 22094073 TI - Implantable cardioverter-defibrillator longevity under clinical circumstances: an analysis according to device type, generation, and manufacturer. AB - BACKGROUND: One of the major drawbacks of implantable cardioverter-defibrillator (ICD) treatment is the limited device service life. Thus far, data concerning ICD longevity under clinical circumstances are scarce. In this study, the ICD service life was assessed in a large cohort of ICD recipients. OBJECTIVE: To assess the battery longevity of ICDs under clinical circumstances. METHODS: All patients receiving an ICD in the Leiden University Medical Center were included in the analysis. During prospectively recorded follow-up visits, reasons for ICD replacement were assessed and categorized as battery depletion and non-battery depletion. Device longevity and battery longevity were calculated. The impact of device type, generation, manufacturer, the percentage of pacing, the pacing output, and the number of shocks on the battery longevity was assessed. RESULTS: Since 1996, 4673 ICDs were implanted, of which 1479 ICDs (33%) were replaced. Mean device longevity was 5.0 +/- 0.1 years. A total of 1072 (72%) ICDs were replaced because of battery depletion. Mean battery longevity of an ICD was 5.5 +/- 0.1 years. When divided into different types, mean battery longevity was 5.5 +/- 0.2 years for single-chamber ICDs, 5.8 +/- 0.1 for dual-chamber ICDs, and 4.7 +/- 0.1 years for cardiac resynchronization therapy-defibrillators (P <.001). Devices implanted after 2002 had a significantly better battery longevity as compared with devices implanted before 2002 (5.6 +/- 0.1 years vs 4.9 +/- 0.2 years; P <.001). In addition, large differences in battery longevity between manufacturers were noted (overall log-rank test, P <.001). CONCLUSIONS: The majority of ICDs were replaced because of battery depletion. Large differences in longevity exist between different ICD types and manufacturers. Modern ICD generations demonstrated improved longevity. PMID- 22094074 TI - A fully automatic, implantable cardioverter-defibrillator algorithm to prevent inappropriate detection of ventricular tachycardia or fibrillation due to T-wave oversensing in spontaneous rhythm. AB - BACKGROUND: T-wave oversensing (TWOS) may cause inappropriate shocks in patients with implantable cardioverter-defibrillator (ICD). Programming options to prevent TWOS are usually implemented only after TWOS has occurred, and they may compromise sensing of ventricular fibrillation (VF). OBJECTIVE: To evaluate an ICD algorithm that differentiates TWOS from ventricular tachycardia (VT) or VF to prevent inappropriate detection of VT/VF when TWOS occurs. METHODS: We developed a TWOS algorithm based on both the differential frequency content of R vs T waves and their alternating pattern. Algorithm parameters were developed from a database of stored electrograms. The algorithm was validated on a hardware system consisting of actual ICD circuitry by using an independent database of stored electrograms including inappropriate detections of both VT/VF caused by spontaneous TWOS and induced true VF to assess delays in detection. RESULTS: We tested 83 inappropriate detections of VF due to TWOS from 22 patients. All 22 patients had at least 1 successful rejection of TWOS, and rejection was effective in 80 of the 83 episodes. After adjustment for multiple episodes per patient, specificity was 96.6% (95% confidence interval 90.3%-98.8%). In 166 episodes of true VF in 92 patients, the sensitivity for VF detection was 100% (95% confidence interval 98.2%-100%) at a nominal sensitivity of 0.3 mV; the new TWOS algorithm did not delay the detection of VF. CONCLUSION: A novel TWOS rejection algorithm is designed to operate in real time. The algorithm reduced inappropriate detections of VF in spontaneous TWOS episodes by 96.6% while maintaining 100% sensitivity for detecting true VF. PMID- 22094075 TI - Renin-angiotensin system blockers are associated with reduced mortality and heart failure hospitalization in patients paced for complete atrioventricular block. AB - BACKGROUND: Right ventricular apical pacing can cause dyssynchronous activation of the ventricles, increase sympathetic activation, cause abnormalities in myocardial perfusion, worsen cardiac output and endothelial function, and may be associated with adverse cardiovascular effects. The use of rennin-angiotensin system blockers (RASBs) may be beneficial in counteracting these potentially harmful effects of right ventricular pacing. OBJECTIVE: To explore the impact of RASB use on the outcome in patients with right ventricular pacemakers implanted for complete atrioventricular (AV) block. METHODS: Patients implanted with right ventricular pacemakers for complete AV block between 1994 and 2009 were identified from the Tayside Pacing Registry. Cox proportional hazards model was used to assess differences in all-cause mortality and congestive heart failure hospitalizations for those receiving RASB during follow-up, adjusted for confounding variables. We also performed 2 sensitivity analyses--a propensity score-matched analysis and time-dependent analyses--to minimize bias. RESULTS: Eight hundred twenty patients (57% men; median age 73 years; range 22-103 years) received pacemakers for complete AV block between 1994 and 2008 (54% dual-chamber pacemaker and 46% ventricular demand pacemaker). Two hundred seventy-eight (34%) patients had received RASBs. Mean follow-up was 4.9 +/- 4.6 years, with 540 (65%) deaths. RASB use was independently associated with significantly reduced mortality (adjusted hazard ratio 0.67; 95% confidence interval 0.47-0.94; P = .017) and reduced heart failure hospitalization (adjusted hazard ratio 0.42; 95% confidence interval 0.17-0.92; P <.001). CONCLUSIONS: This study suggests that RASBs may confer outcome benefits in patients with right ventricular pacemakers implanted for complete AV block. PMID- 22094077 TI - Regulation of foamy viral transcription and RNA export. AB - Foamy viruses (FVs) are distinct members of the retrovirus (RV) family. In this chapter, the molecular regulation of foamy viral transcription, splicing, polyadenylation, and RNA export will be compared in detail to the orthoretroviruses. Foamy viral transcription is regulated in early and late phases, which are separated by the usage of two promoters. The viral transactivator protein Tas activates both promoters. The nature of this early late switch and the molecular mechanism used by Tas are unique among RVs. RVs duplicate the long terminal repeats (LTRs) during reverse transcription. These LTRs carry both a promoter region and functional poly(A) sites. In order to express full-length transcripts, RVs have to silence the poly(A) signal in the 5' LTR and to activate it in the 3' LTR. FVs have a unique R-region within these LTRs with a major splice donor (MSD) at +51 followed by a poly(A) signal. FVs use a MSD-dependent mechanism to inactivate the polyadenylation. Most RVs express all their genes from a single primary transcript. In order to allow expression of more than one gene from this RNA, differential splicing is extensively used in complex RVs. The splicing pattern of FV is highly complex. In contrast to orthoretroviruses, FVs synthesize the Pol precursor protein from a specific and spliced transcript. The LTR and IP-derived primary transcripts are spliced into more than 15 different mRNA species. Since the RNA ratios have to be balanced, a tight regulation of splicing is required. Cellular quality control mechanisms retain and degrade unspliced or partially spliced RNAs in the nucleus. In this review, I compare the RNA export pathways used by orthoretroviruses with the distinct RNA export pathway used by FV. All these steps are highly regulated by host and viral factors and set FVs apart from all other RVs. PMID- 22094076 TI - Why caretakers bypass Primary Health Care facilities for child care - a case from rural Tanzania. AB - BACKGROUND: Research on health care utilization in low income countries suggests that patients frequently bypass PHC facilities in favour of higher-level hospitals - despite substantial additional time and financial costs. There are limited number of studies focusing on user's experiences at such facilities and reasons for bypassing them. This study aimed to identify factors associated with bypassing PHC facilities among caretakers seeking care for their underfive children and to explore experiences at such facilities among those who utilize them. METHODS: The study employed a mixed-method approach consisting of an interviewer administered questionnaires and in-depth interviews among selected care-takers seeking care for their underfive children at Korogwe and Muheza district hospitals in north-eastern Tanzania. RESULTS: The questionnaire survey included 560 caretakers. Of these 30 in-depth interviews were conducted. Fifty nine percent (206/348) of caretakers had not utilized their nearer PHC facilities during the index child's sickness episode. The reasons given for bypassing PHC facilities were lack of possibilities for diagnostic facilities (42.2%), lack of drugs (15.5%), closed health facility (10.2%), poor services (9.7%) and lack of skilled health workers (3.4%). In a regression model, the frequency of bypassing a PHC facility for child care increased significantly with decreasing travel time to the district hospital, shorter duration of symptoms and low disease severity.Findings from the in-depth interviews revealed how the lack of quality services at PHC facilities caused delays in accessing appropriate care and how the experiences of inadequate care caused users to lose trust in them. CONCLUSION: The observation that people are willing to travel long distances to get better quality services calls for health policies that prioritize quality of care before quantity. In a situation with limited resources, utilizing available resources to improve quality of care at available facilities could be more appropriate for improving access to health care than increasing the number of facilities. This would also improve equity in health care access since the poor who can not afford travelling costs will then get access to quality services at their nearer PHC facilities. PMID- 22094078 TI - Diagnosis and control of cereal viruses in the Middle East. AB - Middle Eastern countries are major consumers of small grain cereals. Egypt is the biggest bread wheat producer with 7.4 million tons (MT) in 2007, but at the same time, it had to import 5.9 MT. Jordan and Israel import almost all the grains they consume. Viruses are the major pathogens that impair grain production in the Middle East, infecting in some years more than 80% of the crop. They are transmitted in nonpersistent, semipersistent, and persistent manners by insects (aphids, leafhoppers, and mites), and through soil and seeds. Hence, cereal viruses have to be controlled, not only in the field but also through the collaborative efforts of the plant quarantine services inland and at the borders, involving all the Middle Eastern countries. Diagnosis of cereal viruses may include symptom observation, immunological technologies such as ELISA using polyclonal and monoclonal antibodies raised against virus coat protein expressed in bacteria, and molecular techniques such as PCR, microarrays, and deep sequencing. In this chapter, we explore the different diagnoses, typing, and detection techniques of cereal viruses available to the Middle Eastern countries. We highlight the plant quarantine service and the prevention methods. Finally, we review the breeding efforts for virus resistance, based on conventional selection and genetic engineering. PMID- 22094079 TI - The roles of host factors in tombusvirus RNA recombination. AB - RNA viruses are the champions of evolution due to high frequency mutations and genetic recombination occurring during virus replication. These genetic events are due to the error-prone nature of viral RNA-dependent RNA polymerases (RdRp). Recently emerging models on viral RNA recombination, however, also include key roles for host and environmental factors. Accordingly, genome-wide screens and global proteomics approaches with Tomato bushy stunt virus (TBSV) and yeast (Saccharomyces cerevisiae) as a model host have identified 38 host proteins affecting viral RNA recombination. Follow-up studies have identified key host proteins and cellular pathways involved in TBSV RNA recombination. In addition, environmental factors, such as salt stress, have been shown to affect TBSV recombination via influencing key host or viral factors involved in the recombination process. These advances will help build more accurate models on viral recombination, evolution, and adaptation. PMID- 22094080 TI - Coronavirus pathogenesis. AB - Coronaviruses infect many species of animals including humans, causing acute and chronic diseases. This review focuses primarily on the pathogenesis of murine coronavirus mouse hepatitis virus (MHV) and severe acute respiratory coronavirus (SARS-CoV). MHV is a collection of strains, which provide models systems for the study of viral tropism and pathogenesis in several organs systems, including the central nervous system, the liver, and the lung, and has been cited as providing one of the few animal models for the study of chronic demyelinating diseases such as multiple sclerosis. SARS-CoV emerged in the human population in China in 2002, causing a worldwide epidemic with severe morbidity and high mortality rates, particularly in older individuals. We review the pathogenesis of both viruses and the several reverse genetics systems that made much of these studies possible. We also review the functions of coronavirus proteins, structural, enzymatic, and accessory, with an emphasis on roles in pathogenesis. Structural proteins in addition to their roles in virion structure and morphogenesis also contribute significantly to viral spread in vivo and in antagonizing host cell responses. Nonstructural proteins include the small accessory proteins that are not at all conserved between MHV and SARS-CoV and the 16 conserved proteins encoded in the replicase locus, many of which have enzymatic activities in RNA metabolism or protein processing in addition to functions in antagonizing host response. PMID- 22094082 TI - Mind as a nested operational architectonics of the brain: Comment on "Neuroontology, neurobiological naturalism, and consciousness: a challenge to scientific reduction and a solution" by Todd E. Feinberg. PMID- 22094081 TI - Human immunodeficiency virus viral protein R as an extracellular protein in neuropathogenesis. AB - Numerous studies published in the past two decades have identified the viral protein R (Vpr) as one of the most versatile proteins in the life cycle of human immunodeficiency virus type 1 (HIV-1). In this regard, more than a thousand Vpr molecules are present in extracellular viral particles. Subsequent to viral entry, Vpr participates in early replicative events by assisting in viral genome nuclear import and, during the viral life cycle, by shuttling between the nucleus and the cytoplasm to accomplish its functions within the context of other replicative functions. Additionally, several studies have implicated Vpr as a proapoptotic protein because it promotes formation of permeability transition pores in mitochondria, which in turn affects transmembrane potential and adenosine triphosphate synthesis. Recent studies have identified Vpr as a virion free protein in the serum and cerebrospinal fluid of patients infected with HIV-1 whose plasma viremia directly correlates with the extracellular concentration of Vpr. These observations pointed to a new role for Vpr as an additional weapon in the HIV-1 arsenal, involving the use of an extracellular protein to target and possibly inhibit HIV-1-uninfected bystander cells to enable them to escape immune surveillance. In addition, extracellular Vpr decreases adenosine triphosphate levels and affects the intracellular redox balance in neurons, ultimately causing their apoptosis. Herein, we review the role of Vpr as an extracellular protein and its downstream effects on cellular metabolism, functionality, and survival, with particular emphasis on how extracellular Vpr-induced oxidative stress might aggravate HIV-1-induced symptoms, thus affecting pathogenesis and disease progression. PMID- 22094084 TI - [Preventive of complications after radical prostatectomy]. PMID- 22094083 TI - Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database. AB - Study Type - Prognosis (cohort series). Level of Evidence 2a. What's known on the subject? and What does the study add? The incidence and prevalence of obesity in the USA and Europe is increasing. Higher body mass index is associated with a lower risk of overall prostate cancer diagnosis but also with an increased risk of high grade prostate cancer. Obese men undergoing primary therapy with radical prostatectomy or external beam radiation are more likely to experience a biochemical recurrence after treatment compared with normal weight men. Finally, obesity is associated with increased prostate-cancer-specific mortality. We hypothesized that obese men on androgen deprivation therapy may be at increased risk for prostate cancer progression. Previous studies have shown that obese men have lower levels of testosterone compared with normal weight men. Additionally, one previous study found that obese men have higher levels of testosterone on androgen deprivation therapy. Men with higher levels of testosterone on androgen deprivation therapy are at increased risk of prostate cancer progression. We found that men with higher body mass index were at increased risk of progression to castration-resistant prostate cancer, development of metastases and prostate cancer-specific mortality. When we adjusted for various clinicopathological characteristics, obese men were at increased risk of progression to castration resistant prostate cancer and development of metastases. The results of our study help generate hypotheses for further study regarding the mechanisms between obesity and aggressive prostate cancer. OBJECTIVE: * To investigate whether obesity predicts poor outcomes in men starting androgen deprivation therapy (ADT) before metastasis, since previous studies found worse outcomes after surgery and radiation for obese men. METHODS: * A retrospective review was carried out of 287 men in the SEARCH database treated with radical prostatectomy between 1988 and 2009. * Body mass index (BMI) was categorized to <25, 25-29.9 and >= 30 kg/m2. * Proportional hazards models were used to test the association between BMI and time to castration-resistant prostate cancer (PC), metastases and PC-specific mortality adjusting for demographic and clinicopathological data. RESULTS: * During a median 73-month follow-up after radical prostatectomy, 403 men (14%) received early ADT. * Among 287 men with complete data, median BMI was 28.3 kg/m2. * Median follow-up from the start of ADT was 52 months during which 44 men developed castration-resistant PC, 34 developed metastases and 24 died from PC. * In multivariate analysis, higher BMI was associated with a trend for greater risk of progression to castration-resistant PC (P= 0.063), a more than threefold increased risk of developing metastases (P= 0.027) and a trend toward worse PC specific mortality (P= 0.119). * Prognostic biomarkers did not differ between BMI groups. CONCLUSIONS: * Among men treated with early ADT, our results suggest that obese men may have increased risk of PC progression. * These data support the general hypothesis that obesity is associated with aggressive PC, although validation of these findings and further study of the mechanisms linking obesity and poor PC outcomes are required. PMID- 22094085 TI - [The suggestion of thrombolytic therapy for intermediate risk patients with acute pulmonary embolism]. PMID- 22094086 TI - [Analysis of risk factors for urinary continence after radical prostatectomy]. AB - OBJECTIVE: There are many causative factors for the occurrence of post prostatectomy incontinence. Objective clinical characteristics, surgical techniques and pelvic floor muscle therapy are the most important ones. The present study was to identify the risk factors associated with urinary incontinence after radical retropubic prostatectomy (RRP). METHODS: A total of 263 patients were recruited for this multivariate analysis. After a close follow up, a series of pre-, peri- and post-operative factors were recorded and analyzed. RESULTS: Urinary continence after radical prostatectomy was 14.8% at 4 weeks and 94.7% at 16 weeks. The most important recovery interval for urinary continence was 4 - 16 weeks post-operation. Multivariate analysis revealed that age (P = 0.015), blood transfusion (P = 0.017), previous TURP (transurethral resection of the prostate) (P = 0.006) and neoadjuvant hormonal therapy (P = 0.005) were the important risk factors for urinary incontinence. CONCLUSION: During RRP, optimized preservation of urethral rhabdosphincter length, nerve sparing and early postoperative functional exercises can improve the recovery of urinary continence. Age, blood transfusion and previous TURP are the independent prognostic factors. Neoadjuvant hormonal therapy may improve urinary continence through increasing the preoperative length of membranous urethra. PMID- 22094087 TI - [Influences of erectile functions in benign prostatic hyperplasia patients by two micro (thulium) laser resection of prostate-tangerine technique]. AB - OBJECTIVE: To observe the influences of erectile dysfunction (ED) by age, prostate size and lower urinary tract symptom (LUTS) undergoing two micro (thulium) laser resection of prostate-tangerine technique (TmLRP-TT). METHODS: A total of 50 BPH (benign prostatic hyperplasia) patients underwent TmLRP-TT with a 70 W laser power. The patient prostate volume, international prostatic symptomatic score (IPSS), maximal flow rate and international index of erectile function (IIEF-5) were assessed preoperatively. A retrospective assessment was made after surgery and at a 6-month follow-up. They were divided into 2 groups according to prostate volume <= 50 or > 50 ml, age <= 65 yrs or > 65 yrs, IIEF-5 <= 20 or > 21 and IPSS <= 27 or > 27 respectively. The postoperative influences of erection by age, prostate size and LUTS were observed. RESULTS: Significant differences existed between pre-operation and 6 months post-operation in terms of IPSS (25.35 +/- 5.6 vs 9.52 +/- 3.1, P < 0.01) and maximal flow rate (6.51 +/- 1.21 vs 13.4 +/- 2.7 ml/s, P < 0.01). There was no difference between pre operation and 6 months post-operation (34 vs 32 cases, chi(2) = 0.673, P = 0.603). The patients with prostate volume >50 ml group had 9 additional ED cases while those with IPSS >27 group contained 11 fewer ED cases. There were significant differences between both groups (chi(2) = 5.255, P = 0.002; chi(2) = 11.560, P = 0.001 respectively). BPH patients aged over 65 years old were more likely to suffer ED than those under 65 years old (chi(2) = 5.882, P = 0.015). However, there was no significant difference in age in terms of suffering postoperative ED (chi(2) = 3.125, P = 0.077). CONCLUSION: TmLRP-TT can significantly improve LUTS in BPH patients. The presence of large volume prostate is an independent risk factor for an increased number of ED patients after TmLRP TT. LUTS is an independent risk factor for ED. And TmLRP-TT may improve the ED patients with severe LUTS. PMID- 22094088 TI - [Clinical study of diethylstilbestrol in hormone refractory prostate cancer]. AB - OBJECTIVE: To summarize the clinical outcome and adverse events of estrogen therapy for hormone refractory prostate cancer. METHODS: A total of 32 patients with hormone refractory prostate cancer received diethylstilbestrol (DES) 2 mg daily at our institute. The data of PSA (prostate-specific antigen) change, time to progression, overall survival rate, disease-specific survival rate and adverse events were collected and analyzed. RESULTS: The data of 29 patients were complete. The mean duration of DES dosing was 8.6 +/- 0.9 months. Among them, 8 (27.5%) patients achieved a PSA response with a 50% decrement of PSA or more. Seven (24.1%) patients had a stable level of PSA (50% < PSA < 125%) while 14 of 29 (48.3%) maintained a PSA progression with a 25% increment of PSA or more. The overall median time to progression was 4 (1 - 12) months. And the median time to progression was 6 (5-12) months in the PSA response group. The overall survival rate was 48.3% and disease-specific survival rate 55.2%. The main adverse events were gynecomastia (10/29, 34.5%) and deep vein thrombosis (3/29, 10.3%). CONCLUSION: When used for the treatment of hormone refractory prostate cancer, diethylstilbestrol at a daily dose of 2 mg can achieve a PSA response in 27.5% patients and a PSA stability in 24.1% patients. And the median time to progression is 4 months. Estrogen is efficacious for the patients with hormone refractory prostate cancer. PMID- 22094089 TI - [Differentially expressed urine protein of contrast induced acute kidney injury by two-dimensional differential in-gel electrophoresis and mass spectrometry]. AB - OBJECTIVE: To explore the differentially expressed proteins of contrast-induced nephropathy through a comparison of urinary proteome so as to further elucidate the pathogenesis and discover the disease biomarker. METHODS: The urine samples of 12 patients were collected before and after coronary angiography. Two dimensional electrophoresis was performed after the urine samples were labeled by different dyes. The differences of urine proteome were analyzed by Decyder software and the differentially expressed spots identified by mass spectrometry. RESULTS: A total of 56 differentially expressed spots were detected. Among them, 39 spots were up-regulated and 17 spots down-regulated. And mannose binding lectin and mannose binding lectin associated serine protease 2, key proteins in complement body activation, were both significantly up-regulated. CONCLUSION: Urine proteomic study methods are constructed based on 2D-DIGE and mass spectrometry. The lectin pathway of complement body may be associated with contrast-induced acute kidney injury. PMID- 22094090 TI - [Stratification therapy in patients with acute promyelocytic leukemia after a complete remission by all-trans retinoic acid]. AB - OBJECTIVE: To explore an efficacious protocol for the patients with acute promyelocytic leukemia (APL) after a complete remission (CR) by all-trans retinoic acid (ATRA). METHODS: A total of 32 APL patients with an induction of CR by ATRA at our hospital from January 2000 to October 2007 received conventional standard chemotherapy as a consolidation regimen. Stratified according to age, those under 50 years old received an intermediate dose of cytarabine(IDAra-C)and over 50 years old non-IDAra-C regimen. Maintenance regimen: all patients received ATRA, arsenic trioxide (As2O3) and 6-mercaptopurine (6-MP) + methotrexate (MTX) alternately and sequentially for 3 years. The efficacy and side effects of these chemotherapies were observed. RESULTS: The median follow-up was 72 (40 - 124) months. The 5-year disease-free survival (DFS) rates of under 50 years old and over 50 years old were 94.7% and 92.3% respectively. The difference was statistically insignificant (P > 0.05). One patient relapsed after a consolidation therapy and so did another on a maintenance regimen. Thirty patients achieved a constant CR. And 16 of 30 patients completed chemotherapy beyond 5 years and survived disease-free. The 5-year DFS rate of 32 patients was 93.8%. CONCLUSION: After the achievement of CR with ATRA, all APL patients have a higher rate of DFS after stratification. The side effects are generally mild. Thus a stratification therapy is both feasible and efficacious. PMID- 22094091 TI - [Clinical treatment of application of deep venous thrombosis by retrievable vena cava filter]. AB - OBJECTIVE: To summarize the clinical experiences of treating deep venous thrombosis (DVT) with retrievable vena cava filter. METHODS: A total of 180 patients with DVT in unilateral lower extremity were recruited. There were 82 males and 98 females with an average age of 46 years old. After the diagnosis of vascular color Doppler ultrasound, retrievable vena cava filter was implanted through contralateral femoral vein. Simultaneously another 114 patients underwent femoral vein embolectomy. All cases received the post-operative therapies of anticoagulation, thrombolysis and vasodilation. RESULTS: The implantation of retrievable vena cava filter was successful in all cases. Among 142 cases of attempted extraction, 116 filters were extracted successfully at Days 12 - 24. The success rate was 81.69%. Filters captured thrombosis in 34 cases (29.31%). CONCLUSION: As a safe and efficacious method, the implantation of retrievable vena cava filter prevents the occurrence of pulmonary embolism in the patients with DVT in unilateral lower extremity. Its timely extraction may avoid the long term complications. PMID- 22094092 TI - [Effects of different ventilation mode on pulmonary function during minor operation of general anesthesia with SLIPA laryngeal mask]. AB - OBJECTIVE: To retrospectively analyze the effects of different ventilation modes on pulmonary function during minor operation of general anesthesia with streamlined liner of the pharynx airway (SLIPA) laryngeal mask and assess its safety of spontaneous respiration during general anesthesia. METHODS: A total of 76 adult patients (aged 28 - 44 years old, American Society of Anesthesiologists physical status I-II) scheduled for operations were randomly allocated into the mechanical ventilation and spontaneous respiration group (n = 38 each). Anesthetic induction was performed intravenously with propofol (2 mg/kg), sulfentanyl (0.5 ug/kg) and cisatracurium besylate (0.3 mg/kg) (in mechanical ventilation group). Anesthesia was maintained by sevoflurane at 0.7 minimum alveolar concentration (MAC), mixture of atmosphere and oxygen at 1:1 and a continuous infusion of propofol at the speed of 4 mg*kg(-1)h(-1). Neostigmine (2 mg) and atropine (1 mg) were administered intravenously before the extraction of SLIPA laryngeal mask in order to antagonize the residual effects of muscle relaxation. The parameters including heart rate (HR), mean blood pressure (MAP) and end-tidal pressure of CO(2) (P(ET)CO(2)), blood gas analysis and the alveolar arterial oxygen gradient [P(A-a)DO(2)], respiratory index (RI) and dead volume/tidal volume (V(D)/V(T)) were calculated at Different time points. RESULTS: No significant differences were found in HR (spontaneous respiration group: 76 +/- 7, 78 +/- 6, 79 +/- 7/min; mechanical ventilation group: 77 +/- 6, 80 +/- 5, 79 +/- 6/min), MAP (spontaneous respiration group: 91 +/- 10, 89 +/- 9, 90 +/- 9mm Hg; mechanical ventilation group: 89 +/- 10, 88 +/- 9, 92 +/- 8) mm Hg at the monitored time points between two groups (P > 0.05). At the time of 30 min and 60 min after insertion, the pH value was significantly lower in spontaneous respiration group (7.351 +/- 0.028, 7.338 +/- 0.025) than those in mechanical ventilation group (7.391 +/- 0.031, 7.389 +/- 0.032). The values of PaCO(2) (42 +/- 4, 46 +/- 6) mm Hg and P(ET)CO(2) (41 +/- 5, 45 +/- 3) mm Hg were higher than those in mechanical ventilation group (37 +/- 3, 35 +/- 5; 37 +/- 4, 36 +/- 4) mm Hg (P < 0.05). No significant difference was found in the P(A-a)DO(2), RI or V(D)/V(T) at the monitored time points between two groups (P > 0.05). CONCLUSION: Neither mechanical ventilation mode nor spontaneous respiration ventilation mode has any effect upon pulmonary function by during minor operation of general anesthesia with SLIPA laryngeal mask. Spontaneous respiration can offer a sufficient supply of oxygen but it carries the risk of CO(2) accumulation. PMID- 22094093 TI - [Sevoflurane postconditioning attenuates myocardial apoptosis in isolated rat hearts via a modulation of Bcl-2 family proteins]. AB - OBJECTIVE: To explore the effects of sevoflurane postconditioning on ischemic/reperfused myocardial apoptosis. METHODS: Isolated perfused rat hearts were randomly assigned into 3 groups: sham-operation (sham), ischemia/reperfusion (I/R) and sevoflurane postconditioning (SPC). Except for the sham group, the hearts were subjected to 40 min global myocardial ischemia and 120 min reperfusion. Left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximum increase rate of LVDP (+dp/dt), maximum decrease rate of LVDP (-dp/dt), heart rate (HR) and coronary flow (CF) were measured at baseline, R (reperfusion) 30 min, R60 min, R90 min and R120 min. Creatine kinase (CK) and lactate dehydrogenase (LDH) were measured at 5 min and 10 min post-reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining at the end of reperfusion. The expressions of Bcl-2 and Bax were determined by Western blot. RESULTS: The values of LVSP, LVDP, +/- dp/dt and CF were higher while that of LVEDP was lower in the SPC group than the I/R group at all time points of reperfusion (P < 0.05). The releases of CK and LDH and infarct size were significantly reduced in the SPC group versus the I/R group (22.2% +/- 2.8% vs I/R: 44.9% +/- 6.6%, P < 0.05). The expression of Bcl-2 increased significantly while that of Bax decreased in the SPC group verus the I/R group. CONCLUSION: Sevoflurane postconditioning may improve myocardial functions, reduce infarct size and attenuate myocardial apoptosis. And the modulated expression of apoptotic proteins plays an important role in sevoflurane-induced myocardial protection. PMID- 22094094 TI - [Effect of mesenchymal stem cells on cardiac function and restenosis of injured artery after myocardial infarction]. AB - OBJECTIVE: Although earlier studies have shown that the transplantation of mesenchymal stem cells (MSCs) might improve cardiac functions after myocardial infraction, its role on vascular restenosis after percutaneous coronary intervention (PCI) remains controversial. The aim of this study was to investigate the effects of MSCs on the restenosis of injured artery following balloon angioplasty in a rabbit model with both myocardial infarction reperfusion and atherosclerotic stenosis carotid artery by balloon injury. METHODS: After the animal model was established for myocardial infraction reperfusion and atherosclerotic stenosis carotid artery by balloon injury, the rabbits received an intravenous transplantation of MSCs. And an equal volume of phosphate buffered solution was administered for the control group. The animal vascular tissue and myocardium tissue were excised at different time points post-transplantation and used to detect the homing of MSCs and the expressions of platelet-endothelial cell adhesion molecule-1 (CD31) and proliferating cell nuclear antigen (PCNA) by immunohistochemical staining. Four weeks later, vascular restenosis was analyzed by angiography of bilateral carotid arteries and the vascular tissues were used for histological studies. RESULTS: At one week post-transplantation, the 4',6 diamidino-2-phenylindole (DAPI)-labeled MSCs could be detected in myocardial infarction and injured intima. And the intimal expression of CD31 was observed at 2 weeks in the MSCs transplantation group. Yet the expression of PCNA was significantly lower in the MSCs transplantation group than that in the control group (50.5% +/- 3.6% vs 23.4% +/- 2.8%, P < 0.05). At 4 week post transplantation, the neointimal area of injured vessels and the vascular restenosis were significantly lower in the MSCs transplantation group than those in the control group (0.092 +/- 0.009 vs 0.189 +/- 0.007, P < 0.05; 41.7 +/- 3.7 vs 61.3 +/- 1.6, P < 0.05). Furthermore the MSCs transplantation group demonstrated improved cardiac functions, reduced myocardial infarct size (21.7% +/- 2.2% vs 34.3% +/- 1.8%, P < 0.05) and significantly increased capillary density around infarction foci (33.6% +/- 2.1% vs 20.8% +/- 2.6%, P < 0.05) versus the control group. CONCLUSION: The transplantation of MSCs plays significant roles in cardiac repairing in terms of improved cardiac functions, accelerated repair of injured vessels, suppression of neointimal hyperplasia and reduced restenosis of injured vessels. PMID- 22094095 TI - [Mechanisms of focal adhesion kinase in the proliferation of human pulmonary artery smooth cells under hypoxia]. AB - OBJECTIVE: To explore the mechanisms of focal adhesion kinase (FAK) in the proliferation of human pulmonary artery smooth muscle cells (HPASMCs) under hypoxia. METHODS: Cultured HPASMCs were passively transfected with FAK oligonucleotides (ODNS) and under normoxia or hypoxia condition. They were divided into four groups: normoxia without fibronectin (FN), normoxia with FN, hypoxia without FN, hypoxia with FN in vitro respectively. Cytoplasmic FAK, Grb2 and paxillin were observed simultaneously by immunoprecipitation and Western blot. In addition, the expressions of cytoplasmic FAK, Grb2 and paxillin were detected by immunocytochemical staining. RESULTS: Immunoprecipitation and Western blot demonstrated that cytoplasmic expressions of FAK, Grb2 and paxillin in HPASMCs increased in hypoxia with FN from 43.4 +/- 1.4, 69.7 +/- 1.9, 59.3 +/- 1.6 to 35.7 +/- 1.2, 48.7 +/- 1.3, 33.2 +/- 1.8 at 1.5 h (all P < 0.05), from 41.3 +/- 1.3, 71.3 +/- 1.5, 59.4 +/- 1.8 to 41.3 +/- 1.3, 50.2 +/- 1.7, 38.9 +/- 1.9 at 24 h respectively (P < 0.01, P < 0.05, P < 0.05). Immunocytochemistry staining showed that the cytoplasmic expressions of FAK, Grb2 and paxillin were enhanced in hypoxia with FN versus normoxia with FN. There were significant differences. CONCLUSION: Hypoxia can induce the activation of cytoplasmic FAK, Grb2 and paxillin so as to regulate the migration, survival and proliferation of HPASMCs. PMID- 22094096 TI - [Inhibitory effects of zoledronic acid on cell proliferation and invasion in human nasopharyngeal carcinoma cell line HNE1]. AB - OBJECTIVE: To explore the in vitro anti-tumor effects of zoledronic acid on cell proliferation and invasion in human nasopharyngeal carcinoma cell line HNE1. METHODS: The cytotoxic effects of zoledronic acid on HNE1 cells were detected by MTT assay, invasion of HNE1 cells by Transwell assay, secretion of (vascular endothelial growth factor)VEGF by (enzyme-linked immunosorbent assay) ELISA and the activities of MMP (matrix metalloproteinase) 2 and MMP9 by gelatine zymography. And the expressions of mRNA and proteins of MMP2, MMP9 and VEGF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. RESULTS: After a treatment of zoledronic acid at 2.5, 5, 10, 20 and 40 mol/L for 48 h or 72 h, the highest inhibition rate of proliferation at approximately 50% was observed in the 40 mol/L group after 72 h. The inhibitory effect was not in a dose/time-dependent manner. After a 24-hour treatment of zoledronic acid at different concentrations (0, 10, 20 and 40 mol/L), the numbers of membrane-invading cells were 75.8 +/- 2.6, 54.8 +/- 5.4, 44.6 +/- 6.4 and 38.6 +/- 8.2 respectively (all P < 0.01). Gelatinase zymography demonstrated that the activities of MMP2 and MMP9 were inhibited significantly only in cells treated at 0 umol/L. After a 24-hour exposure to zoledronic acid at 0, 10, 20 and 40 umol/L, the concentrations of VEGF in supernatant were (5264 +/- 89), (4626 +/- 30), (4155 +/- 40) and (1908 +/- 171) g/L respectively (all P < 0.01). The expressions of mRNA and protein of MMP2, MMP9 and VEGF were down-regulated. CONCLUSION: Zoledronic acid can inhibit the in vitro proliferation and invasion of HNE1 cell through suppressing the secretion of VEGF, the activities of MMP2 and MMP9 and the expressions of VEGF, MMP2 and MMP9. PMID- 22094097 TI - [Protective effects of erythromycin on human bronchial epithelial cells impaired by interleukin-4]. AB - OBJECTIVE: To study the protective effects and mechanisms of erythromycin on human bronchial epithelial (HBE) cells damaged by interleukin-4. METHODS: The growth curve of HBE cells was recorded by MTT. The cells were divided into the following groups: control (incubation for 24, 48 h); IL-4 (0.01 mg/L, incubation for 24, 48 h); erythromycin intervention group 1 (4 mg/L erythromycin co incubation for 24, 48 h after adding IL-4) and erythromycin intervention group 2 (40 mg/L erythromycin co-incubation for 24, 48 h after adding IL-4). The mitotic cycle of HBE cell was determined by flow cytometry and its apoptosis examined by Hoechst dyeing. RESULTS: The viability of HBE cells was significantly enhanced after a 24/48-hour treatment of erythromycin as compared with IL-4 group (P < 0.05, P < 0.01). In erythromycin intervention group 1, the cell ratios of G(0)/G(1) and S phases were (55.9 +/- 2.5)% and (34.7 +/- 3.4)% respectively while the rate of cell apoptosis was (9.5 +/- 0.9)%. There were significant differences as compared with IL-4 group (P < 0.05). In erythromycin intervention group 2, the cell ratios of G(0)/G(1) and S phases were (55.1 +/- 0.5)% and (36.2 +/- 2.7)% respectively while the rate of cell apoptosis was (4.0 +/- 0.6)%. There were significant differences as compared with IL-4 group (P < 0.05). CONCLUSION: Erythromycin has protective effects on HBE cells damaged by IL-4. The mechanism is probably through influencing the mitotic cycle and inhibiting the apoptosis. PMID- 22094098 TI - [Effect of RAD001 or plus LBH589 on the proliferation, apoptosis and drug resistance in chemoresistant acute myeloid leukemic cells]. AB - OBJECTIVE: To investigate the effects of everolimus (RAD001) or plus panobinostat (LBH589) on the proliferation, apoptosis and drug resistance in chemoresistant acute myeloid leukemic cells. METHODS: HL-60/ADM cells were treated with RAD001 alone or with LBH589. Proliferation and apoptosis were evaluated by 3-(4,5) dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, Hoechst33342 and AnnexinV-FITC/PI stain. The altered expressions of multidrug resistance associated protein 1 (MRP1) and intercellular adriamycin accumulation were analyzed by flow cytometry. The change in protein level was analyzed by Western blot. RESULTS: Effective proliferative inhibition and apoptotic induction in HL60/ADM cells were observed in the treatment of 10 - 50 umol/L RAD001. The maximal effect was shown for the concentration of 30 umol/L RAD001 at 48 and 72 hours. The inhibition ratio remained unchanged with the adjustment of drug doses (P < 0.05). Moreover, there was no synergistic effects in the treatment with different concentration of RAD001 and LBH589 (CI >= 1.0). A down-regulation of MRP1 (93.9% +/- 4.2% vs 79.10 +/- 3.28%) and an up-regulation of adriamycin (8.53 +/- 0.68% vs 15.37% +/- 1.46%) were induced by the treatment with 10 umol/L RAD001 (both P < 0.01). RAD001 inhibited the p53-dependent expression of MRP1 via an inhibition of phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling pathway. CONCLUSION: The combined treatment of RAD001 and LBH589 has no synergistically inhibitory effect on HL60/ADM cells. But the sole treatment of RAD001 may inhibit proliferation, induce apoptosis and accumulate intercellular adriamycin through a down-regulated expression of MRP1 in HL60/ADM cells via an inhibition of PI3K/Akt/mTOR signaling pathway. PMID- 22094099 TI - [Genotyping for CYP2C19 with multiplex PCR point mutation screening technology]. AB - OBJECTIVE: To establish a multiplex PCR point mutation screening technique for the genotyping of CYP2C19. METHODS: Deoxyinosine multiplex-polymerase chain reaction (PCR) primers (DMPs) were designed to detect simultaneously CYP2C19*1,*2,*3 alleles in one PCR tube. RESULTS: The above technique could detect the genotypes of CYP2C19*1, CYP2C19*2 and CYP2C19*3 successfully. And the results were completely consistent with those of DNA sequencing. CONCLUSION: A novel screening technique of multiplex PCR point mutation is successfully established. With the advantages of high specificity, convenient handling, fast completion and low cost, it provides a reasonable and reliable detection method for basic researches and personalized medicine. PMID- 22094100 TI - Retention of different-sized particles and derived gut fill estimate in tammar wallabies (Macropus eugenii): physiological and methodological considerations. AB - The capacity of the digestive tract is an important parameter in understanding digestive adaptations, particularly in herbivores. Measures of this capacity ('gut fill') are commonly performed in killed animals, which has ethical and logistical implications. Alternatively, dry matter gut contents (DMC) can be estimated in live animals from food intake, digesta retention and digestibility, based on physical principles (Holleman and White, Can. J. Zool. 67, 488-494, 1989). Although this method has been used to some extent, it still awaits thorough validation. Here we estimated DMC in seven tammar wallabies during 5-day feeding trials and compared the results to those gained from dissections immediately after the trials. Calculated DMC exceeded that actually measured by 29 +/- 22%. A closer inspection of the data suggested that this was partly due to the fact that DMC as measured by dissection is susceptible to short-term influences such as daily variation in food intake, whereas the calculated DMC represents an integrative measure over the whole period of the feeding trial. Correlations between both the measured digesta retention times, and the calculated DMC, with the measured wet contents mass suggest that it is particularly the DMC determined via dissection that needs to be measured with care. For a comparison of gut capacities, the calculated DMC therefore can be considered adequate, but should for a more widespread use be validated in further studies including more species and experimental regimes controlling food intake variation. Additionally, we tested whether very small (100-500 MUm) and small (500-1000 MUm) particles were retained differently in the tammar wallabies. There was no indication of such a difference. Whether the macropod forestomach selectively passes a certain particle fraction (that represents microbes) with the generally faster-passing fluids remains to be investigated with even smaller markers, e.g. labelled bacteria. PMID- 22094101 TI - Risk perception and social participation among women exposed to manganese in the mining district of the state of Hidalgo, Mexico. AB - OBJECTIVE: To analyze the importance attributed to manganese (Mn) in the health disease-death process and possibilities for participation in risk management of women from two communities who live near the plant in the Molango mining district. MATERIALS AND METHODS: Qualitative study based on 6 focus groups with women of different ages. Audio recordings were made of the sessions, after verbal informed consent, and were transcribed with a word processor. The analysis was conducted according to theme, taking into account the age group and community to which the women belonged, using the Atlas-ti (v.5.0) program. RESULTS: The youngest women from Chiconcoac attribute the cause of headaches and chest pain to manganese, while women from the Tolago community believe it exacerbates disease in general. Women between 31 and 40 years old from Chiconcoac attribute the cause of "brain" pain, burning eyes and coughs to manganese, and those in Tolago report that it causes memory problems. The oldest women in Tolago believe Mn causes learning difficulties and affects children's growth and development. The women of all ages in Tolago believe that Mn has decreased the production of fruit and vegetables in the region. Some of the obstacles to participation in risk management are: women are not allowed to attend meetings at which men discuss the Mn problem and they perceive the mine as a source of employment for the community. CONCLUSIONS: The women perceive Mn to have serious effects on health and the local environment and have fewer opportunities than men to participate in risk management. Some of the health consequences attributed to Mn are consistent with those reported by neurological studies, nevertheless, other risks are overestimated. Spaces for communication need to be created to listen to the women's interests and concerns and empower them to participate in the risk management plan. PMID- 22094102 TI - Protection against TNFalpha-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFalpha in vivo. AB - Tumor necrosis factor-alpha (TNFalpha) is a classic proinflammatory cytokine implicated in the pathogenesis of several autoimmune and inflammatory diseases including viral encephalitis. Macrophages being major producers of TNFalpha are thus attractive targets for in vivo RNA interference (RNAi) mediated down regulation of TNFalpha. The application of RNAi technology to in vivo models however presents obstacles, including rapid degradation of RNA duplexes in plasma, insufficient delivery to the target cell population and toxicity associated with intravenous administration of synthetic RNAs and carrier compounds. We exploited the phagocytic ability of macrophages for delivery of Dicer-substrate small interfering RNAs (DsiRNAs) targeting TNFalpha (DsiTNFalpha) by intraperitoneal administration of lipid-DsiRNA complexes that were efficiently taken up by peritoneal macrophages and other phagocytic cells. We report that DsiTNFalpha-lipid complexes delivered intraperitoneally altered the disease outcome in an acute sepsis model. Down-regulation of TNFalpha in peritoneal CD11b+ monocytes reduced liver damage in C57BL/6 mice and significantly delayed acute mortality in mice treated with low dose LPS plus d-galactosamine (D-GalN). PMID- 22094103 TI - Polyethyleneimine-based core-shell nanogels: a promising siRNA carrier for argininosuccinate synthetase mRNA knockdown in HeLa cells. AB - RNA interference using small interfering RNA (siRNA) is a promising biological strategy for treatment of diverse diseases; however, application of siRNA is severely hindered by its poor stability and low cellular uptake efficiency. We have recently demonstrated that polyethyleneimine (PEI)-based amphiphilic core shell particles have several distinguishing advantages over native PEI and its derivatives. This paper presents a novel type of PEI-based nanogels with a biodegradable gelatin core. The core-shell nanogels were synthesized via a two stage reaction: (1) preparation of highly uniform gelatin nanoparticles through appropriate treatment of gelatin solution; and (2) conjugation of branched PEI to the preformed gelatin nanoparticles, followed by repeated cycles of desolvation and drying of the gelatin-PEI nanogels in ethanol/water mixture. The resulting nanogels have a well-defined nanostructure that contains a gelatin core and a PEI shell. They have an average diameter of 200 +/- 40nm with high uniformity. The nanogel particles possess positive zeta-potential values of up to +40mV at neutral pH, indicating that they are highly positive and very stable in aqueous medium. The gelatin-PEI nanogels were able to completely condense siRNA at N/P ratios of as low as 5:1, and effectively protected siRNA against enzymatic degradation. Furthermore, the nanogels were four times less toxic than native PEI. Besides low toxicity, the nanogels were able to effectively deliver siRNA into HeLa cells. It was found that increasing the N/P ratio from 10 to 30 significantly increased the intracellular uptake efficiency of siRNA from 41 to 84%. Confocal laser scanning microscopic images confirmed that the nanogels were able to effectively deliver siRNA in the cytoplasm of HeLa cells. The delivered siRNA could inhibit 70% of human argininosuccinate synthetase 1 (ASS1) gene expression. This gene silencing percentage is much higher than that of the commercial Lipofectamine(TM) 2000. Our studies demonstrate that gelatin-PEI core shell nanogels have promising potential to act as an effective siRNA carrier. PMID- 22094104 TI - State of the art in PEGylation: the great versatility achieved after forty years of research. AB - In the recent years, protein PEGylation has become an established and highly refined technology by moving forward from initial simple random coupling approaches based on conjugation at the level of lysine epsilon-amino group. Nevertheless, amino PEGylation is still yielding important conjugates, currently in clinical practice, where the degree of homogeneity was improved by optimizing the reaction conditions and implementing the purification processes. However, the current research is mainly focused on methods of site-selective PEGylation that allow the obtainment of a single isomer, thus highly increasing the degree of homogeneity and the preservation of bioactivity. Protein N-terminus and free cysteines were the first sites exploited for selective PEGylation but currently further positions can be addressed thanks to approaches like bridging PEGylation (disulphide bridges), enzymatic PEGylation (glutamines and C-terminus) and glycoPEGylation (sites of O- and N-glycosylation or the glycans of a glycoprotein). Furthermore, by combining the tools of genetic engineering with specific PEGylation approaches, the polymer can be basically coupled at any position on the protein surface, owing to the substitution of a properly chosen amino acid in the sequence with a natural or unnatural amino acid bearing an orthogonal reactive group. On the other hand, PEGylation has not achieved the same success in the delivery of small drugs, despite the large interest and several studies in this field. Targeted conjugates and PEGs for combination therapy might represent the promising answers for the so far unmet needs of PEG as carrier of small drugs. This review presents a thorough panorama of recent advances in the field of PEGylation. PMID- 22094105 TI - Complement system and the brain: selected pathologies and avenues toward engineering of neurological nanomedicines. AB - Several nanoparticle systems and supramolecular assemblies are under investigation as potential therapeutic entities for Alzheimer's disease and other neurological disorders through both brain-specific targeting and peripheral effects. However, activation of the complement system, a complex innate immune network of over 30 circulating and membrane-bound proteins, remains a serious concern related to the use of these prospective neurological nanomedicines. The role of complement in processes of neurodegeneration in the injured or aged and diseased central nervous system is well known. Nanoparticle-mediated complement activation cannot only induce adverse cardiopulmonary distress in sensitive subjects, but may further aggravate the already-compromised condition of neurological disorders and diseases. This minireview briefly examines the role of complement in neurological diseases and outlines the current status of the development of key neurological nanomedicines with respect to complement activation. Understanding of these topics is crucial for rational design and development of safe neurological nanomedicines. PMID- 22094106 TI - Albendazole sensitizes cancer cells to ionizing radiation. AB - BACKGROUND: Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. METHODS: Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP ribose) polymerase (PARP) cleavage. RESULTS: ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. CONCLUSIONS: Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted. PMID- 22094107 TI - Curtains up! Using forum theatre to rehearse the art of communication in healthcare education. AB - Teaching students to develop high quality communication skills in healthcare education is vitally important if best practice is to be achieved. These skills have often been seen as challenging to successfully develop. Didactic approaches impart knowledge but not necessarily the opportunities to practice communication techniques. This paper shares the experiences of a group of University lecturers introducing the use of an experiential theatrical technique, forum theatre, to support students to develop their communication skills. Forum theatre aims to create a dynamic learning environment enabling students to try out different communication strategies within a safe setting. Academic staff perform short scripted scenes developed using their knowledge from practice along with the experience of carers and service users. The end result is always unsatisfactory for the service user. The scene is then re-run inviting the students to interact with the characters and to change the outcome to a positive one resulting in a collaborative experience. PMID- 22094108 TI - The use of skills inventories to assess and grade practice: Part 1--design and implementation. AB - Employers increasingly require evidence of competent practice and cost-effective education that is fit for purpose. Historically, universities providing nurse education have been more concerned with the testing and grading of theory at undergraduate level which ultimately defines degree classification. This may be at the expense of recognising excellence in clinical practice which should be the ultimate goal of any nurse education programme. This paper reviews the development and introduction of an assessment tool to grade clinical competence in higher education level 6 post-registration critical care courses using a skills-based assessment strategy. The knowledge and practice components for each skill are defined within a standardised template. A number of skills pertinent to the area of practice and academic module are then collected in a skills inventory for assessment and grading which contribute to degree classification. PMID- 22094110 TI - Longitudinal hypothalamic-pituitary-adrenal axis trait and state effects in recurrent depression. AB - BACKGROUND: Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity has been observed in (recurrent) major depressive disorder (MDD), although inconsistently and mainly cross-sectional. Longitudinal studies clarifying state-trait issues are lacking. We aimed to determine whether HPA-axis (hyper)activity in recurrent MDD is: (I) reflecting a persistent trait; (II) influenced by depressive state; (III) associated with stress or previous episodes; (IV) associated with recurrence; and (V) influenced by cognitive therapy. METHODS: We included 187 remitted highly recurrent MDD-patients (mean number of previous episodes: 6.3), participating in a randomized-controlled-trial investigating the preventive effect of additional cognitive therapy on recurrence. In an add-on two-staged patient-control and prospective-cohort design, we first cross-sectionally compared patients' salivary morning and evening cortisol concentrations with 72 age- and sex-matched controls, and subsequently longitudinally followed-up the patients with repeated measures after three months and two years. RESULTS: Patients had higher cortisol concentrations than controls (p<.001), which did not change by MDD-episodes during follow-up. HPA-axis activity had no relation with daily hassles or childhood life events. Cortisol concentrations were lower in patients with more previous episodes (p=.047), but not associated with recurrence(s) during follow-up. Finally, randomly assigned cognitive therapy at study-entry enhanced cortisol declines over the day throughout the two-year follow-up (p=.052). CONCLUSIONS: Our results indicate that remitted recurrent MDD patients have a persistent trait of increased cortisol concentrations, irrespective of stress. In combination with our finding that patients' cortisol concentrations do not change during new MDD-episodes (and thus not represent epiphenomenal or state-effects), our results support that hypercortisolemia fulfills the state-independence criterion for an endophenotype for recurrent depression. PMID- 22094109 TI - Interprofessional education: innovation in action. PMID- 22094111 TI - Meal anticipation potentiates postprandial ghrelin suppression in humans. AB - Circulating concentrations of the orexigenic hormone ghrelin show a postprandial decrease in dependence on meal size and composition. Cognitive determinants of postprandial ghrelin suppression in humans are largely unexplored. We assessed the effects of cued meal anticipation on pre- and postprandial concentrations of total plasma ghrelin, pancreatic polypeptide and leptin as well as on markers of glucose metabolism in healthy men. In a between-subject comparison, meal anticipation was induced in 14 fasted men at 08:00 h by the announcement and subsequent presentation of a breakfast buffet. Fifteen fasted control subjects were informed that they would remain fasted until noon. At 10:00 h, both groups were served a rich free-choice breakfast. At 12:00 h, all subjects underwent a snack test assessing casual cookie intake. Circulating concentrations of ghrelin, pancreatic polypeptide, glucose, insulin and leptin were frequently assessed. Preprandial endocrine parameters as well as breakfast intake (all p>0.23) and subsequent snack consumption (p>0.83) were comparable between groups. The postprandial suppression of ghrelin levels observed in both groups was markedly stronger in subjects who had anticipated breakfast intake (p<0.03) while pancreatic polypeptide concentrations did not differ between groups (p>0.56). Results indicate that meal anticipation is a critical determinant of postprandial ghrelin suppression that, as suggested by unaltered pancreatic polypeptide levels, appears to be mediated independent of vagal activation. Our findings highlight the role of subtle cognitive factors in the postprandial regulation of ghrelin secretion, suggesting that neurobehavioral approaches to improved food intake control should take into account meal anticipatory mechanisms. PMID- 22094112 TI - A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF. AB - The protein p14ARF is a known tumor suppressor protein controlling cell proliferation and survival, which mainly localizes in nucleoli. However, the regulatory mechanisms that govern its activity or expression remain unclear. Here, we report that a novel proapoptotic nucleolar protein, PANO, modulates the expression and activity of p14ARF in HeLa cells. Overexpression of PANO enhances the stability of p14ARF protein by protecting it from degradation, resulting in an increase in p14ARF expression levels. Overexpression of PANO also induces apoptosis under low serum conditions. This effect is dependent on the nucleolar localization of PANO and inhibited by knocking-down p14ARF. Alternatively, PANO siRNA treated cells exhibit a reduction in p14ARF protein levels. In addition, ectopic expression of PANO suppresses the tumorigenicity of HeLa cells in nude mice. These results indicate that PANO is a new apoptosis-inducing gene by modulating the tumor suppressor protein, p14ARF, and may itself be a new candidate tumor suppressor gene. PMID- 22094113 TI - Epigenetic and transcriptional control of the 15-lipoxygenase-1 gene in a Hodgkin lymphoma cell line. AB - Lipoxygenases oxidatively metabolize polyunsaturated fatty acids to a rich spectrum of biologically active metabolites. The present study aimed at delineating the transcriptional and epigenetic mechanisms leading to 15 lipoxygenase-1 (15-LOX-1) expression in the Hodgkin lymphoma (HL) cell line L1236. Examination of the 15-LOX-1 5' promoter region demonstrated three putative binding sites for signal transducer and activator of transcription (STAT6) within the proximal 1200 base pairs relative to the start codon. Analysis by serial promoter deletions and STAT6 binding site mutations indicated that all three STAT6 binding sites are required for full activation of the 15-LOX-1 promoter. Chromatin immunoprecipitation assay demonstrated that these regions were occupied by STAT6 in L1236 (15-LOX-1 positive) but not in L428 (15-LOX-1 negative) cultured HL cells. Furthermore, DNA hypomethylation and histone hyperacetylation were detectable within the core promoter region of 15-LOX-1 only in L1236 cells but not L428 cells. Taken together, our data indicate that STAT6 activation and chromatin remodeling by DNA demethylation and histone acetylation are crucial for transcriptional activation of 15-LOX-1 in cultured HL cells. These prerequisites are fulfilled in the L1236 cell line, but not in the L428 cell line. PMID- 22094114 TI - Advances in Arachis genomics for peanut improvement. AB - Peanut genomics is very challenging due to its inherent problem of genetic architecture. Blockage of gene flow from diploid wild relatives to the tetraploid; cultivated peanut, recent polyploidization combined with self pollination, and the narrow genetic base of the primary genepool have resulted in low genetic diversity that has remained a major bottleneck for genetic improvement of peanut. Harnessing the rich source of wild relatives has been negligible due to differences in ploidy level as well as genetic drag and undesirable alleles for low yield. Lack of appropriate genomic resources has severely hampered molecular breeding activities, and this crop remains among the less-studied crops. The last five years, however, have witnessed accelerated development of genomic resources such as development of molecular markers, genetic and physical maps, generation of expressed sequenced tags (ESTs), development of mutant resources, and functional genomics platforms that facilitate the identification of QTLs and discovery of genes associated with tolerance/resistance to abiotic and biotic stresses and agronomic traits. Molecular breeding has been initiated for several traits for development of superior genotypes. The genome or at least gene space sequence is expected to be available in near future and this will further accelerate use of biotechnological approaches for peanut improvement. PMID- 22094115 TI - "There's no kind of respect here" A qualitative study of racism and access to maternal health care among Romani women in the Balkans. AB - INTRODUCTION: Roma, the largest minority group in Europe, face widespread racism and health disadvantage. Using qualitative data from Serbia and Macedonia, our objective was to develop a conceptual framework showing how three levels of racism--personal, internalized, and institutional--affect access to maternal health care among Romani women. METHODS: Eight focus groups of Romani women aged 14-44 (n = 71), as well as in-depth semi-structured interviews with gynecologists (n = 8) and key informants from NGOs and state institutions (n = 11) were conducted on maternal health care seeking, experiences during care, and perceived health care discrimination. Transcripts were coded, and analyzed using a grounded theory approach. Themes were categorized into domains. RESULTS: Twenty-two emergent themes identified barriers that reflected how racism affects access to maternal health care. The domains into which the themes were classified were perceptions and interactions with health system, psychological factors, social environment and resources, lack of health system accountability, financial needs, and exclusion from education. CONCLUSIONS: The experiences of Romani women demonstrate psychosocial and structural pathways by which racism and discrimination affect access to prenatal and maternity care. Interventions to address maternal health inequalities should target barriers within all three levels of racism. PMID- 22094116 TI - Evaluation of the evidence on staging imaging for detection of asymptomatic distant metastases in newly diagnosed breast cancer. AB - While guidelines recommend against routine use of staging imaging to detect asymptomatic distant metastases (DM) in newly diagnosed breast cancer (BC), modern imaging technologies may have improved detection capability and may have a role in some cases. We performed a systematic review of studies (1995-2011) evaluating the prevalence of DM and the accuracy of staging imaging for detection of asymptomatic DM. Twenty-two studies reporting on 14,824 BC subjects (median age 53 years) undergoing staging imaging were eligible. Median prevalence of DM was 7.0% (range 1.2-48.8%); prevalence increased with increasing BC stage. Conventional imaging studies had lower DM prevalence than studies of PET(PET/CT). Imaging median sensitivity/specificity respectively were: combined conventional imaging 78.0%/91.4%; bone scintigraphy 98.0%/93.5%; chest X-ray 100%/97.9%; liver ultrasound 100%/96.7%; CT chest/abdomen 100%/93.1%; FDG-PET 100.0%/96.5%; FDG PET/CT 100%/98.1%. Low prevalence of DM was seen in Stage I-II BC with much higher prevalence in more advanced disease. Accuracy of PET modalities was very high however the high proportion of detected asymptomatic DM partly reflects selection bias. PMID- 22094117 TI - Polymorphisms of genes involved in extracellular matrix remodeling and abdominal aortic aneurysm. AB - BACKGROUND: Abdominal aortic aneurysm (AAA) has a multifactorial etiology and the relevance of genetic factors is getting increasing interest, in particular those related to the destructive remodeling of extracellular matrix. METHODS: We performed a candidate gene association study of polymorphisms in genes coding matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), and elastin (ELN) in AAA. DNA samples from 423 AAA patients and 423 controls were genotyped for 12 polymorphisms in 10 genes: MMP1 (-1607G/GG), MMP2 (-735C/T; -1306C/T; 1575 G/A), MMP3 (5A/6A), MMP9 (-1562C/T), MMP10 (A180G), MMP-12 (-82A/G), MMP-13 (-77A/G), TIMP1 (C434T), TIMP3 (-1296T/C), and ELN (G1355A). RESULTS: Genotype distribution was significantly different between patients and controls for the following polymorphisms: -1306C/T MMP2; 5A/6A MMP3; -77A/G MMP-13; G1355A ELN; and C434T TIMP1. In a multivariable logistic regression analysis adjusted for traditional cardiovascular risk factors and chronic obstructive pulmonary disease, -1306C/T MMP2 (odds ratios [OR] = 0.55 [95% confidence interval, CI .34 .85], P < .007) and G1355A ELN (OR = 0.64 ([95% CI .41-.99], P = .046) polymorphisms resulted in independent protective factors for abdominal aortic aneurysm (AAA), whereas 5A/6A MMP3 (OR = 1.82 [95% CI 1.04-3.12], P = .034) and 77 A/G MMP-13 (OR = 2.14 [95% CI 1.18-3.86], P = .012) polymorphisms resulted in independent risk factors for AAA. In a multivariable logistic regression analysis adjusted for traditional cardiovascular factors and chronic obstructive pulmonary disease, the prevalence of the contemporary presence of three or four genetic risk conditions was a strong and independent determinant of AAA disease (OR = 2.96, 95% CI 1.67-5.24, P < .0001). For those polymorphisms independently associated with AAA in this study (-1306C/T MMP2, 5A/6A MMP3, -77A/G MMP-13, and G1355A ELN polymorphisms), we performed a meta-analysis of the available data (this paper and literature data). We found a significant association with an increased risk of AAA for MMP3 (AAA patients n = 1258, controls n = 1406: OR = 1.48 [95% CI = 1.23-1.78], I(2) = 0%) and MMP-13 (AAA patients n = 800, controls n = 843: OR = 1.37 [95% CI = 1.04-1.82], I(2) = 25%) polymorphisms and a trend that did not reach the statistical significance, toward a decreased risk of AAA for MMP2 (AAA patients n = 1090, controls n = 1077: OR = 0.83 [95% CI = .60 1.15], I(2) =7 1%) and ELN (AAA patients n = 904, controls n = 1069: OR = 0.79 [95% CI = .53-1.18], I(2) = 72%) polymorphisms. CONCLUSIONS: These findings suggest that polymorphisms in MMP2, MMP3, MMP-13, and ELN genes may independently contribute to the pathogenesis of AAA. PMID- 22094119 TI - Effect of increasing energy cost on arm coordination in elite sprint swimmers. AB - The purpose of this study was to analyze the changes in stroke parameters, motor organization and swimming efficiency with increasing energy cost in aquatic locomotion. Seven elite sprint swimmers performed a 6*300-m incremental swimming test. Stroke parameters (speed, stroke rate and stroke length), motor organization (arm stroke phases and arm coordination index), swimming efficiency (swimming speed squared and hand speed squared) and stroke index were calculated from aerial and underwater side-view cameras. The energy cost of locomotion was assessed by measuring oxygen consumption and blood lactate. Results showed that the increase in energy cost of locomotion was correlated to an increase in the index of coordination and stroke rate, and a decrease in stroke length (p<.05). Furthermore, indicators of swimming efficiency and stroke index did not change significantly with the speed increments (p<.05), indicating that swimmers did not decrease their efficiency despite the increase in energy cost. In parallel, an increase in the index of coordination IdC and stroke rate were observed, along with a decrease in stroke length, stroke index and hand speed squared with each increment, revealing an adaptation to the fatigue within the 300m. PMID- 22094118 TI - Motor abundance supports multitasking while standing. AB - Many activities require simultaneous performance of multiple tasks. Motor redundancy may provide a key mechanism for multitasking, ensuring minimal inter task interference. This study investigated the effect of performing two supra postural tasks on postural stability. The component of joint configuration variance (JCV) reflecting flexible joint combinations (V(UCM)) that stabilize the center of mass (CoM) position and the component of JCV leading to variability (V(ORT)) of the CoM were determined using the Uncontrolled Manifold (UCM) approach. Subjects executed a targeting task alone or in combination with a ball balancing task. UCM analysis revealed that the joints were coordinated such that their combined variance reflected primarily V(UCM), without a substantial effect on CoM position stability. Evidence for this flexible control strategy increased when the ball-balancing task was added to targeting, or when the index of difficulty of targeting increased, both without leading to substantial increases in V(ORT) or CoM position variance. The increase in joint variance when performing additional tasks without affecting adversely CoM position stability supports the hypothesis that the nervous system takes advantage of available motor redundancy for the successful performance of multiple tasks concurrently. Future work is needed to investigate the limits of this control scheme. PMID- 22094120 TI - Novel micelles based on amphiphilic branched PEG as carriers for fenretinide. AB - This study reports on the preparation and evaluation of amphiphilic macromolecules based on branched polyethylene glycol covalently linked with alkyl hydrocarbon chains. These macromolecules easily dissolved in an aqueous environment, with formation of micellar nanoaggregates endowed with hydrophobic inner cores capable of hosting fenretinide by complexation. The complexes increased fenretinide aqueous solubility, while hindering its release as a free drug in an aqueous environment. Particle size analysis indicated dimensional suitability of the complexes for intravenous administration. Neuroblastoma cell lines (SH-SY5Y and NGP) exhibited increased sensitivity to fenretinide in complex as compared to free drug, associated with higher intracellular concentrations of fenretinide observed after treatment with the complex. Transmission electronic microscopy images revealed endocytosis of the micellar complex. Moreover, fenretinide conversion to its metabolite 4-oxo-fenretinide was delayed in cells treated with the complex, further supporting the hypothesis that fenretinide may be absorbed by micellar transport and exposed to the cytoplasm for conversion to its metabolite only after micelle destabilization. PMID- 22094121 TI - New strategy of efficient inhibition of cancer cells by carborane carboxylic acid CdTe nanocomposites. AB - Nanoconjugates composed of drug molecules encapsulated in quantum dots (QDs) attract enormous attention due to their promising bioimaging and biomedical applications. Here, the anticancer efficiency of potential pharmacophore agents (o-carborane (Cb), o-carborane-C-carboxylic acid (Cbac1), and o-carborane C(1)C(2)-dicarboxylic acid (Cbac2) coupling with cadmium telluride QDs capped with cysteamine (CA-CdTe QDs)) have been explored. Compared with free CA-CdTe QDs, the composites consisting of Cbac1/Cbac2 and safe-dosage QDs can greatly improve the inhibition efficiency toward SMMC-7721 hepatocellular carcinoma cells with the aid of our real-time cell bioelectronic sensing system and the MTT assay. The enhanced cytotoxicity correlates with increased intracellular reactive oxygen species generation and cell apoptosis. Confocal laser scanning fluorescent microscopy shows improved cellular uptake and drug distribution of the Cbac1/Cbac2-CdTe QDs nanoconjugates. This work raises the possibility that the carborane pharmacophore in combination with QDs or other anticancer drugs may be viable for efficient cancer diagnosis and chemotherapy. PMID- 22094122 TI - Mutagenic effects of gold nanoparticles induce aberrant phenotypes in Drosophila melanogaster. AB - The peculiar physical/chemical characteristics of engineered nanomaterials have led to a rapid increase of nanotechnology-based applications in many fields. However, before exploiting their huge and wide potential, it is necessary to assess their effects upon interaction with living systems. In this context, the screening of nanomaterials to evaluate their possible toxicity and understand the underlying mechanisms currently represents a crucial opportunity to prevent severe harmful effects in the next future. In this work we show the in vivo toxicity of gold nanoparticles (Au NPs) in Drosophila melanogaster, highlighting significant genotoxic effects and, thus, revealing an unsettling aspect of the long-term outcome of the exposure to this nanomaterial. After the treatment with Au NPs, we observed dramatic phenotypic modifications in the subsequent generations of Drosophila, demonstrating their capability to induce mutagenic effects that may be transmitted to the descendants. Noteworthy, we were able to obtain the first nanomaterial-mutated organism, named NM-mut. Although these results sound alarming, they underline the importance of systematic and reliable toxicology characterizations of nanomaterials and the necessity of significant efforts by the nanoscience community in designing and testing suitable nanoscale surface engineering/coating to develop biocompatible nanomaterials with no hazardous effects for human health and environment. FROM THE CLINICAL EDITOR: While the clinical application of nanomedicine is still in its infancy, the rapid evolution of this field will undoubtedly result in a growing number of clinical trials and eventually in human applications. The interactions of nanoparticles with living organisms determine their toxicity and long-term safety, which must be properly understood prior to large-scale applications are considered. The paper by Dr. Pompa's team is the first ever demonstration of mutagenesis resulting in clearly observable phenotypic alterations and the generation of nano mutants as a result of exposure to citrate-surfaced gold nanoparticles in drosophila. These groundbreaking results are alarming, but represent a true milestone in nanomedicine and serve as a a reminder and warning about the critical importance of "safety first" in biomedical science. PMID- 22094123 TI - Cancer cell response to nanoparticles: criticality and optimality. AB - A stochastic variation in size and electrical parameters is common in nanoparticles. Synthesizing gold nanoparticles with a varying range of size and zeta potential, we show that there is clustering at certain regions of hydrodynamic diameter and zeta potentials that can be classified using k clustering technique. A cluster boundary was observed around 50 nm, a size known for its optimal response to cells. However, neither size nor zeta potential alone determined the optimal cellular response (e.g., percentage cell survival) induced by such nanoparticles. A complex interplay prevails between size, zeta potential, nature of surface functionalization, and extent of adhesion of the cell to a solid matrix. However, it follows that the ratio of zeta potential to surface area, which scales as the electrical field (by Gaussian law), serves as an appropriate indicator for optimal cellular response. The phase plot spanned by fractional survival and effective electric field (charge density) indicates a positive correlation between mean cell survival and the magnitude of the electric field. The phase plot spanned by fractional survival and effective electric field (charge density) associated with the nanosurface shows a bifurcation behavior. Wide variation of cell survival response is observed at certain critical values of the surface charge density, whereas in other ranges the cellular response is well behaved and more predictable. Existence of phase points near the critical region corresponds to wide fluctuation of nanoparticle-induced response, for small changes in the nanosurface property. Smaller nanoparticles with low zeta potential (e.g., those conjugated with arginine) can have such an attribute (i.e., higher electrical field strength), and eventually they cause more cell death. The study may help in optimal design of nanodrugs. PMID- 22094125 TI - A united approach to European neurology. PMID- 22094124 TI - Human electrophysiological correlates of learned irrelevance: effects of the muscarinic M1 antagonist biperiden. AB - Learned irrelevance (LIrr) refers to a reduction in associative learning after pre-exposure of the conditioned and unconditioned stimulus in a non-contingent fashion. This paradigm might serve as a translational model for (pre)attentive information processing deficits in schizophrenia. This is the first study to investigate the event-related potentials (ERPs) of a within-subject LIrr paradigm in humans. Furthermore, the effects of the muscarinic M1 antagonist biperiden on LIrr were assessed. As expected, LIrr was found to be intact in young healthy volunteers after placebo. Furthermore, in the placebo condition P3b latency was decreased for target stimuli, which were pre-cued. This suggests that the predictability of the occurrence of these stimuli is mainly reflected by this ERP component. Biperiden had no effect on the behavioural LIrr measures, although prolonged reaction times were evident. Biperiden increased the N1 amplitude of the pre-exposed predictor letters, suggesting an effect of this drug on early perceptual processing. In conclusion, the within-subject paradigm used in the current study in combination with electroencephalography can reveal brain mechanisms involved in LIrr. M1 antagonism did not affect LIrr performance but seemed to influence early information processing. PMID- 22094126 TI - The virtual neurologist. PMID- 22094127 TI - Francesc Graus: solving paraneoplastic puzzles. PMID- 22094129 TI - Familial amyloid polyneuropathy. AB - Familial amyloid polyneuropathies (FAPs) are a group of life-threatening multisystem disorders transmitted as an autosomal dominant trait. Nerve lesions are induced by deposits of amyloid fibrils, most commonly due to mutated transthyretin (TTR). Less often the precursor of amyloidosis is mutant apolipoprotein A-1 or gelsolin. The first identified cause of FAP-the TTR Val30Met mutation-is still the most common of more than 100 amyloidogenic point mutations identified worldwide. The penetrance and age at onset of FAP among people carrying the same mutation vary between countries. The symptomatology and clinical course of FAP can be highly variable. TTR FAP typically causes a nerve length-dependent polyneuropathy that starts in the feet with loss of temperature and pain sensations, along with life-threatening autonomic dysfunction leading to cachexia and death within 10 years on average. TTR is synthesised mainly in the liver, and liver transplantation seems to have a favourable effect on the course of neuropathy, but not on cardiac or eye lesions. Oral administration of tafamidis meglumine, which prevents misfolding and deposition of mutated TTR, is under evaluation in patients with TTR FAP. In future, patients with FAP might benefit from gene therapy; however, genetic counselling is recommended for the prevention of all types of FAP. PMID- 22094130 TI - Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. AB - Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular autoimmune disease that has served as a model for autoimmunity and tumour immunology. In LEMS, the characteristic muscle weakness is thought to be caused by pathogenic autoantibodies directed against voltage-gated calcium channels (VGCC) present on the presynaptic nerve terminal. Half of patients with LEMS have an associated tumour, small-cell lung carcinoma (SCLC), which also expresses functional VGCC. Knowledge of this association led to the discovery of a wide range of paraneoplastic and non-tumour-related neurological disorders of the peripheral and central nervous systems. Detailed clinical studies have improved our diagnostic skills and knowledge of the pathophysiological mechanisms and association of LEMS with SCLC, and have helped with the development of a protocol for early tumour detection. PMID- 22094131 TI - Modelling of Parkinson's disease in mice. AB - Although progress has been made in the symptomatic treatment of Parkinson's disease since the discovery of L-dopa in the 1960s, no neuroprotective therapy is yet available. Absence of adequate animal models of the disease that enable prediction of clinical success of potential treatments is often cited as a major impediment to progress and discourages researchers and pharmaceutical companies from investing resources to develop such treatments. Classic models are still widely used, but have been disappointing, and development of genetic models has given new hope. However, can a human disease be faithfully reproduced in a mouse? In this Review we summarise evidence that some genetic mouse models do reproduce key features of Parkinson's disease and show that much can be learned from even imperfect models. The hope is that this information could be used to advance the search for neuroprotective therapies for Parkinson's disease. PMID- 22094133 TI - Ambient temperature affects thrombotic potential at rest and following exercise. AB - INTRODUCTION: During exercise, ischemic risk increases, possibly due to changes in coagulation and fibrinolytic activity. Previous research suggests ambient temperature affects resting thrombotic potential, but the effect of heat and cold on hemostasis during exercise is unknown. The purpose of this study was to assess changes in coagulation and fibrinolysis during maximal exercise in hot and cold temperatures, and to compare those responses to exercise under temperate conditions. MATERIALS & METHODS: Fifteen healthy men completed maximal exercise tests in hot (30 degrees C), temperate (20 degrees C) and cold (5 degrees - 8 degrees C) temperatures. Blood samples were obtained before and immediately after exercise and analyzed for concentrations of thrombin-antithrombin III (TAT), active tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). Results were analyzed by ANOVA. RESULTS: A main effect of time was observed for TAT (temperate=1.71 +/- 0.82 - 2.61 +/- 0.43 ng/ml, hot=1.81 +/- 0.73 - 2.62 +/- 0.67 ng/ml, cold=2.33 +/- 0.65 - 2.89 +/- 0.81 ng/ml, PRE to POST, respectively) and tPA activity (temperate=0.72 +/- 0.44 - 2.71 +/- 0.55 IU/ml, hot=0.72 +/- 0.38 - 2.64 +/- 0.61 IU/ml, cold=0.86 +/- 0.45 - 2.65 +/- 0.77 IU/ml, PRE to POST, respectively). A trend was observed for the PAI-1 response to exercise (temperate=14.5 +/- 23.7 - 12.3 +/- 20.2I U/ml, hot=15.1 +/- 26.5 - 10.0 +/- 15.1 IU/ml, cold=10.5 +/- 10.4 - 7.9 +/- 9.7 IU/ml, PRE to POST, respectively, p=0.08). TAT concentrations were significantly higher in cold compared to temperate and hot conditions. CONCLUSION: Coagulation potential is elevated during exposure to cold temperatures. These data suggest that risk of an ischemic event may be elevated in the cold. PMID- 22094132 TI - The pleiotropic effects of erythropoietin in infection and inflammation. AB - Erythropoietin (EPO) is a multi-functional cytokine, which exerts erythropoietic effects but also carries anti-apoptotic and immune-modulatory activities upon binding to two distinct receptors which are expressed on erythroid, parenchymal and immune cells, respectively. Whereas EPO ameliorates hemolytic anemia in malaria or trypanosomiasis and improves the course of autoimmune diseases such as inflammatory bowel disease or autoimmune encephalomyelitis, it deleteriously inhibits macrophage functions in Salmonella infection in animal models. Thus, the specific modulation of extra-erythropoietic EPO activity forms an attractive therapeutic target in infection and inflammation. PMID- 22094134 TI - How the immune response to vaccines is created, maintained and measured: addressing patient questions about vaccination. AB - This article gives an overview of the immune response to vaccines, including ways in which it is measured and/or augmented to enhance its effectiveness. A brief description is given of the immune response, adaptive immunity, immunologic memory, antibodies, and adjuvants. Given that many young parents and physicians have never witnessed the ravages of vaccine-preventable diseases, it is hoped this article will aid the many people involved in the prevention of infectious disease to understand better the concepts and practicalities of immunization and vaccine development. PMID- 22094136 TI - Adult vaccination. AB - Immunization has effectively decreased the burden of disease on society. Nevertheless, over 50,000 deaths occur annually in the United States from vaccine preventable disease, and nearly all of these occur in adults. It is essential for primary care physicians to be knowledgeable about the unique immunization-related needs of adults and to be aware of the factors that determine the need for vaccination. PMID- 22094135 TI - Routine pediatric immunization, special cases in pediatrics: prematurity, chronic disease, congenital heart disease: recent advancements/changes in pediatric vaccines. AB - Vaccination is a powerful and dynamic weapon in reducing the impact of infectious diseases in children. The field and schedules are constantly evolving, with significant changes resulting in new and exciting vaccines almost yearly. Special cases in pediatrics represent unique challenges and differences in vaccinations. Health care providers need to be knowledgable about the current vaccines and to remain up to date with the constant evolution, as well as be aware of the latest recommendations, warnings, and news about vaccines and their use. This article updates and discusses current but ever-changing routine pediatric vaccination programs. PMID- 22094137 TI - Vaccine-preventable diseases and foreign-born populations. AB - According to the most recent census data, foreign-born individuals account for more than 12% of the US population. Because many vaccine-preventable outbreaks in the United States have been correlated with disease importation, Congress has mandated vaccinations for numerous immigrant populations. It is essential for primary care physicians to be knowledgeable about the unique immunization-related needs of foreign-born individuals to recognize some of the cultural and linguistic challenges that immigrants have accessing health care and to remember to use each medical encounter as an opportunity to provide necessary vaccinations. PMID- 22094138 TI - Immunization in travel medicine. AB - The specialty of travel medicine encompasses a broad and dynamic practice. A thorough pretravel consultation provides an individual with a comprehensive, evidence-based, contextual discussion of the risk profile for specific itinerary based, travel-related illness and injury, allowing the traveler to use this information in conjunction with his or her personal health belief model, risk tolerance, and experience to decide on an informed management plan. This article focuses on the pretravel consultation with emphasis on the contribution of immunization to traveler's health. PMID- 22094139 TI - Passive immunization. AB - Passive immunization employs preformed antibodies provided to an individual that can prevent or treat infectious diseases. There are several situations in which passive immunization can be used: for persons with congenital or acquired immunodeficiency, prophylactic administration when there is a likelihood of exposure to a particular infection, or treatment of a disease state already acquired by the individual. Passive immunization is limited by short duration (typically weeks to months), variable response, and adverse reactions. This article focuses on specific immunoglobulins for preventing or treating infectious diseases, as these are the most likely scenarios one might encounter in primary care practice. PMID- 22094140 TI - The course and management of the 2009 H1N1 pandemic influenza. AB - The 2009 influenza A (H1N1) pandemic provided a major test to the public health system in the United States and abroad. Although the virus was rapidly identified, it took longer than expected to bring an effective vaccine to market. During the interim the virus demonstrated a predilection for infecting younger persons, particularly those with medical conditions such as asthma or pregnancy, placing them at risk. Early treatment with neuraminidase inhibitors was found to be of some benefit. When the 2009 H1N1 influenza A vaccine became available, there were distribution issues in matching the number of doses to areas of need. PMID- 22094141 TI - Cancer vaccines. AB - The term cancer vaccines encompasses 2 different types of vaccines. Prophylactic vaccines block infection by viruses that can alter host DNA and result in cancer. The hepatitis B vaccine and the human papillomavirus vaccines are examples of prophylactic vaccines that can prevent cancer from developing. More recently, therapeutic vaccines have been developed and used as adjunctive therapy in patients who have already been diagnosed with cancer. Therapeutic vaccines stimulate the host's immune system to recognize cancer cells as foreign and to attack them. Most of the therapeutic vaccines being studied are used in combination with other forms of cancer therapy. PMID- 22094142 TI - Vaccination refusal: ethics, individual rights, and the common good. AB - Among the obstacles to the success of vaccination programs is the apparent recent increase in hesitancy and outright resistance to the recommended vaccination schedule by some parents and patients. This article reviews the spectrum of patient or parental attitudes that may be described as vaccine refusal, explores related ethical considerations in the context of the doctor-patient relationship and public health, and evaluates the possible responses of physicians when encountering resistance to vaccination recommendations. Health care providers should view individuals hesitant about or opposed to vaccines not as frustrations or threats to public health, but as opportunities to educate and inform. PMID- 22094143 TI - Office immunization. AB - Nothing has improved disease control as thoroughly as immunizations. In well immunized populations, there is no flaccid paralysis (polio), almost no epiglottitis or postmeningitis deafness (Haemophilus influenzae), and little postviral male sterility (mumps). Immunizations are not perfect; they may cause side effects, some of which have led to the discontinuation of the vaccine when side effects have outweighed the vaccine's protective effects. However, immunization works best not by the protection it provides the individual but by the protection provided to the population at risk. This article discusses the currently available vaccines along with recommendations for their use. PMID- 22094144 TI - Keeping up-to-date with immunization practices. AB - This article presents sources of information for those in practice, administration, or education to stay up-to-date in vaccine recommendations. Web based repositories predominate in the provision of information. Other sources include newsletters, conferences, journals, expert opinion, community organizations, and books. The promise of the electronic health record remains unfulfilled but improving. PMID- 22094145 TI - Q & A: patient to physician FAQs: answers to common patient questions about vaccinations. AB - This article outlines common questions about vaccinations that patients ask their physicians and provides answers to those questions. PMID- 22094146 TI - Immunizations as the nucleus of prevention. PMID- 22094147 TI - Vaccine science: a critical field in the control of diseases. Preface. PMID- 22094148 TI - [Effect of different propranolol doses on skeletal structural and mechanic efficiency in an animal model of growth retardation]. AB - OBJECTIVE: To assess in a growth retardation (GR) model the impact of different propranolol (P) doses on anthropomorphometric and biomechanical variables of the appendicular skeleton. MATERIALS AND METHODS: Twenty-one day-old male Wistar rats were divided into the following groups: control (C), C+P3.5 (CP3.5); C+P7 (CP7); C+P10.5 (CP10.5); C+P14 (CP14); ED, ED+P3.5 (EDP3.5); ED+P7 (EDP7); ED+P10.5 (EDP10.5), and ED+P14 (EDP14). Control animals with/without P were fed a rodent diet ad libitum. GR rats with/without P were given 80% of the same diet per 100g body weight for 4 weeks (T4). Propranolol 3.5, 7, 10.5, and 14 mg/kg/day was intraperitoneally injected 5 days/week for 4 weeks to the CP3.5 and EDP3.5; CP7 and EDP7; CP10.5 and EDP10.5, and CP14 and EDP14 groups respectively. RESULTS: At T4, energy restriction had negative effects upon overall growth, femur, and its mechanical competence. Propranolol improved bone rigidity in GR animals at doses of 7 and 10.5mg/kg/day, with a maximum response at 7 mg/kg/day. CONCLUSIONS: Propranolol 7 mg/kg/day would be the most effective dose for modeling incorporation of bone, as shown by the increased skeletal structural and mechanic efficiency in this animal model of growth retardation. Such effect may result from maintenance of mechanosensor viability, changes in its sensitivity, the biomechanical reference point and/or effector response in GR rats. PMID- 22094149 TI - [Glucocentricity or adipocentricity: a critical view of consensus and clinical guidelines for the treatment of type 2 diabetes mellitus]. AB - Eighty percent of patients with type 2 diabetes mellitus (T2DM) are overweight or obese, which in turn is associated with other cardiovascular risk factors and an increased risk of cancer. Large intervention studies focused on intensive glycemic control have failed to show a reduction of cardiovascular events in T2DM patients. The two major concerns in these studies were weight gain and severe hypoglycemia in the arms of intensive intervention, which could have mitigated the potential beneficial effect of glycemic control. On the contrary, weight loss in diabetic patients through changes in lifestyle, drugs and/or surgery simultaneously improves all cardiovascular risk factors including hyperglycemia. Bariatric surgery has shown an early resolution of T2DM in a large percentage of patients and a decrease of diabetes-specific mortality. Despite this, all consensus and recommendations for the treatment of T2DM focus their decisions on the glycated hemoglobin value. This article aims to open a debate on the need to replace the glucose-centered therapeutic strategy for a weight-centered strategy. PMID- 22094150 TI - Including the third dimension: a spatial analysis of TB cases in Houston Harris County. AB - To reach the tuberculosis (TB) elimination goals established by the Institute of Medicine (IOM) and the Centers for Disease Control and Prevention (CDC), measures must be taken to speed the currently stagnant TB elimination rate and curtail a future peak in TB incidence. Increases in TB incidence have historically coincided with immigration, poverty, and joblessness; all situations that are currently occurring worldwide. Effective TB elimination strategies will require the geographical elucidation of areas within the U.S. that have endemic TB, and systematic surveillance of the locations and location-based risk factors associated with TB transmission. Surveillance data was used to assess the spatial distribution of cases, the yearly TB incidence by census tract, and the statistical significance of case clustering. The analysis revealed that there are neighborhoods within Houston/Harris County that had a heavy TB burden. The maximum yearly incidence varied from 245/100,000-754/100,000 and was not exclusively dependent of the number of cases reported. Geographically weighted regression identified risk factors associated with the spatial distribution of cases such as: poverty, age, Black race, and foreign birth. Public transportation was also associated with the spatial distribution of cases and census tracts identified as high incidence were found to be irregularly clustered within communities of varied SES. PMID- 22094152 TI - Current concepts review: carpal injuries - fractures, ligaments, dislocations. AB - An overview about current concepts in treating carpal injuries is presented. These injuries are more commonly seen in young, active individuals after a fall on an outstretched hand. Conventional radiographs and a thorough examination are important. The scaphoid is the most affected bone. Scaphoid fractures can be classified in accordance to OTA, AO, and other classification systems, but mostly to Herbert. It can be treated non-operatively if undisplaced, however a percutaneous internal fixation can be discussed to achieve earlier return to work and shorter time to union, but hazarding the consequences of an operation. Unstable, proximal pole, or delayed diagnosed scaphoid fractures should be treated surgically. Nonunion is seen in 5 - 40% of scaphoid fractures depending mainly on displacement and localization of the fracture. The gold standard in non osteoarthritic scaphoid nonunion is debridement of the nonunion site, bone grafting, realignment, stable fixation and rehabilitation. The treatment of scaphoid-nonunion advanced collapse is more complex. Proximal row carpectomy or arthrodesis (four-corner or complete wrist) can be mandatory. Other carpal bone fractures are rare. Perilunate dislocations are also uncommon but can be disabling. They usually originate in high-energy trauma. The Mayfield stages help to understand the injury pattern. Open reduction through both volar and dorsal approaches, repair of the volar capsule as well as volar and dorsal ligaments, and internal fixation is commonly the standard treatment. However osteoarthritis and carpal instability are often encountered. PMID- 22094151 TI - ChiZ levels modulate cell division process in mycobacteria. AB - We have previously shown that expression of chiZ (Rv2719c), encoding a cell wall hydrolase, is upregulated in response to DNA damaging agents and exposure to cephalexin. Furthermore, increased levels of ChiZ lead to decreased viability, loss of membrane integrity and defects in FtsZ-GFP localization and cell division. We now show that ChiZ N'-terminal 110 amino acid region, containing the cell wall hydrolase activity, is sufficient to modulate FtsZ-GFP localization. Further, we found that FtsZ-GFP rings are stabilized in a chiZ deletion strain indicating that ChiZ activity regulates FtsZ assembly. Overexpression of ftsZ did not reverse the reduction in viability caused by overproduction of ChiZ indicating that ChiZ neither interacts with nor directly influences FtsZ assembly. Bacterial two-hybrid assays revealed that ChiZ interacts with FtsI and FtsQ, two other septasomal proteins, but not with FtsZ. Finally, we show that ChiZ is not required for virulence of Mycobacterium tuberculosis in murine macrophages and mice. Our data suggest that optimal levels and activity of the cell wall hydrolase ChiZ are required for regulated cell division in mycobacteria. PMID- 22094153 TI - Biomechanical comparison of an interspinous device and a rigid stabilization on lumbar adjacent segment range of motion. AB - PURPOSE OF THE STUDY: Decompression surgery with or without fusion is the gold standard treatment of lumbar spinal stenosis, but adjacent segment degeneration has been reported as a long-term complication after fusion. This led to the development of dynamic implants like the interspinous devices. They are supposed to limit extension and expand the spinal canal at the symptomatic level, but with reduced effect on the range of motion of the adjacent segments. The aim of the present study is the evaluation of the biomechanical effects on the range of motion (ROM) of adjacent lumbar segments after decompression and instrumentation with an interspinous device compared to a rigid posterior stabilization device. MATERIALS AND METHODS: Eight fresh frozen human cadaver lumbar spines (L2-L5) were tested in a spinal testing device with a moment of 7.5 Nm in flexion/extension, lateral bending and rotation with and without a preload. The preload was applied as a follower load of 400N along the curvature of the spine. The range of motion (ROM) of the adjacent segments L2/L3 and L4/L5 was measured with the intact segment L3/L4, after decompression, consisting of resection of the interspinous ligament, flavectomy and bilateral medial facetecomy, and insertion of the Coflex(r) (Paradigm Spine, Wurmlingen) and after instrumentation with Click X(r) (Synthes, Umkirch) as well. RESULTS: The interspinous and the rigid device caused a significant increase of ROM at both adjacent segments during all directions of motion and under follower load, without significant difference between these devices. The ROM of L2/L3 tends to increase more than the ROM of L4/L5 after instrumentation without statistical significance. DISCUSSION: The "dynamic" Coflex device caused a significant increase of ROM at both adjacent lumbar segments comparable to the increase of ROM after instrumentation with the rigid Click X device. Other in vitro studies observed comparable biomechanical effects on the adjacent segments after fusion, but biomechanical spacer studies concentrated on the "noncompressible" X-Stop(r) and could not demonstrate a significant adjacent segment effect of this device. CONCLUSIONS: The hypothesis, that an interspinous device would reduce the stress on adjacent segments compared to a rigid posterior stabilization device, could not be demonstrated with this biomechanical in vitro study. Therefore, the protection of adjacent segments after instrumentation with dynamic devices is still not completely achieved. PMID- 22094154 TI - Serum-cobalt levels with metal-on-metal bearings in the cement-free total hip arthroplasty results covering two years; prospective study. AB - PURPOSE OF THE STUDY: Total hip arthroplasty increases the use of alternate bearings to prevent polyethylene wear as the number of younger and more active patients has drastically risen. We carried out a prospective randomized study, to assess and compare clinical results and radiological changes, serum-cobalt- and serum-aluminium-levels when metal-on-metal and ceramic-on-ceramic bearings are applicated. MATERIAL AND METHODS: After giving informed consent 80 consecutive patients were included in this prospective randomized study. They were randomly assigned to receive either a metal-on-metal or a ceramic-on-ceramic bearing in their total hip replacement. Eligible were patients with a primary coxarthrosis or an avascular necrosis of the head of femur. Of the 80 patients 54 were females and 26 males. 42 patients were randomized to a metal-on-metal bearing and 38 patients were randomized to a ceramic-on-ceramic bearing. The average patient-age was 65,8 years and the mean body mass index was 27,7 at the time of operation. Surgery was performed through a transgluteal approach in supine position under general or spinal anaesthesia. A forged conical threaded acetabular component made of titanium-aluminium-niobium alloy was used in all patients. The metal inlays and the 28 mm metal heads were made of Co-28Cr-6Mo alloy with a carbon content of 0,2%. The ceramic inlays and the 28 mm ceramic heads are Al2O3 implants. We used as femoral component a conical rectangular stem of a titanium aluminium-niobium alloy. Cup and stem werde implanted cementfree. Clinical data werde obtained at a follow up at a minimum of two years after implantation. Patients were assessed with the Harris Hip Score and the University of California at Los Angeles activity scale. 72 of the 80 patients could be explored clinically and radiologically. RESULTS: The 2 year follow up check showed clinically and radiologically no difference between the two groups. The median Harris HipScore was above 90 points and the UCLA score was about 7 points. The medium serum cobalt level was in the metal-on-metal group about 1.2MUg/L and in the ceramic-on ceramic group below the detection limit. The medium serum aluminium level showed values of 1.2 respectively 1.3 MUg/L. The luminescencies in the metal-on-metal group were increased, but all components of the prosthesis could be regarded as stable. DISCUSSION: It was the goal of our prospective study to compare clinical and radiological results of hip arthroplasty in metal-on-metal and ceramic-on ceramic bearings and assess the serum-cobalt and the serum-aluminium levels. The socalled "biocorrosion" is still a high risk element for loosening of implants because of aseptic osteolysis. A higher release of polyethylene and metal particles is triggered, which leads to a slow but continuous process of inflammation. Apart from the debris also metal ions in a higher concentration are released, so that we could detect after some years in patients with artificial implants a higher level of metal in blood and urine. So far we did not recognize any carcinogenity or the appearance of renal disorders, or other mutagene effects in our patients. We could also not observe any fractures in ceramic implants. We are convinced that short time and intermediate reports are necessary, although final judgement can only be based on long term data. CONCLUSION: Our prospective randomized study showed after two years no difference clinically between the two groups of metal-on-metal and ceramic-on-ceramic bearings with total endoprostheses of the hip. Although medium serum-cobalt level in the metal-on metal group with 1,2u/L is a significant higher value, whereas it lies in the ceramic-on-ceramic group below the detectable limit. PMID- 22094155 TI - [Cement-within-cement femoral stem reimplantation technique]. AB - PURPOSE OF THE STUDY: The reimplantation of a cemented femoral component at revision is always a challenge for the orthopaedic surgeon, particularly when the cement mantle is intact. The aim of this study was to provide evidence that the recementing of a femoral stem into the original cement mantle can be included in routine surgical procedures. MATERIAL AND METHODS: A group of 104 patients with femoral stem revision, followed-up for an average of 50.2 months, were retrospectively reviewed. The outcome evaluation was focused, in the first place, on survivorship of the femoral component, acetabular migration, and dislocation and infection after revision arthroplasty. Hip function evaluation was based on the Harris hip scores before surgery and at the latest follow-up. On radiographs Gruen zones were assessed pre-operatively and at the latest follow-up. The results were statistically evaluated using the Kaplan-Meier survival analysis (Statistica 8.0). RESULTS: Of the 104 patients, only three (2.9 %) had stem re revision due to its loosening. Further 16 patients underwent revision for other post-operative complications. The success rate of reimplantation in our group including all post-operative complications was 81.7 %. The average Harris scores were 56 before surgery and 87 at the latest follow-up. Radiolucent lines in Gruen zones were on average 0.45 mm in width before revision and 0.15 mm at the latest follow-up. Fourteen patients had second revision within 20 months of the first and only five were revised after a long period. DISCUSSION: The cement-within cement exchange of a femoral component is a relatively frequent orthopaedic procedure. Despite this frequency, however, there have not been enough literature reports based on large patient groups to give support to its routine use. The aim of this study was to demonstrate on a large patient group that recementing a femoral stem into the original intact cement mantle can be considered an established operative technique. Our results suggest that the list of indications for this technique, as described by Lieberman and Nelson, can be extended by the following: broken stem with an intact distal cement mantle, replacement of a monoblock femoral component due to severe head damage, loosening of the femoral component without impairment of the distal cement mantle, conversion of a cervico capital to a total hip replacement and the need of removing all bone cement. No risk is associated with reimplantation of the original component if there is no need for a different implant to correct angle or length stability. A new implant is always used when any part of the femoral component has been damaged mechanically. If only the proximal stem requires recementing, the use of the original component is preferred because of absolute cement/stem cohesion. The number of our patients in which the technique failed was generally in agreement with the results of other authors. CONCLUSIONS: Utilisation of the original cement mantle of a femoral component is one of the options at revision arthroplasty. It requires rational considerations based on the type of surgery, state of the cement mantle, and type of material used for the femoral stem. The method is indicated preferably in the hips with an intact cement mantle treated for loosening of the acetabular component, recurrent dislocation or unequal leg length in monoblock femoral components. In such situations the removal of well fixed cement would also involve a considerable loss of bone tissue. The follow-up outcomes showed that the involvement of the cement-within-cement technique in routinely used surgical procedures is fully justified. PMID- 22094156 TI - [Total elbow replacement in patients with rheumatoid arthritis]. AB - PURPOSE OF THE STUDY: Total elbow arthroplasty is associated with a higher occurrence of complications than is usual for large-joint replacements. Two kinds of prostheses, unconstrained and semi-constrained, are currently used and each has its supporters or opponents. In this study the results of the two techniques used in our patients are evaluated and compared. MATERIAL: Two groups of elbows in patients with rheumatoid arthritis were evaluated. One comprised 58 elbows treated by Souter-Strathclyde total elbow arthroplasty (S-S group). The mean age of the patients at the time of surgery was 53 years (range, 22 to 71) and the mean follow-up was 9.5 years (range, 0.7 to 16.7). The other group included 63 elbows treated by Coonrad-Morrey elbow arthroplasty (C-M group). The mean age of the patients at the time of surgery was 54 years (range, 26 to 75) and the mean follow-up was 4.21 years (range, 0.28 to 7.87). METHODS: The Kaplan-Meier analysis was used to estimate implant survival in each group. Clinical assessment included range of motion and pain experience. The Mayo Elbow Performance Score (MEPS) was used as a clinical rating scale for the whole group. Radiographs were taken in two basic projections. The elbows with an implant removed or re implanted were excluded from the evaluation. The patients were studied prospectively. The results were statistically analysed, with the level of significance set at 0.05. RESULTS: All patients experienced pain relief after surgery. In the S-S group, 35 elbows were free from pain (77.7 %), in the C-M group this was 53 elbows (88.3 %). The range of motion improved after arthroplasty in both groups. Flexion more than 110 degrees was achieved in twice as many elbows in the C-M group than in the S-S group. Flexion contracture in the S-S group did not improve significantly. MEPS values after surgery improved in both groups, with significantly better results in the C-M group. In the S-S group, four elbow arthroplasties (6.9 %) showed instability, which was treated by replacement with a semi-constrained implant in one case and managed by articulated external fixation of the elbow for 6 weeks in three cases. Radiolucent lines were detected in five replacements (11.1 %) along the whole ulnar component width, in 12 (26.6 %) in the olecranon region and in 14 (31.1 %) in the distal humeral component. In the C-M group no radiolucency was recorded around the component. In the S-S group, revision surgery was carried out in 13 arthroplasties (22.4 %); of these, 10 (17.2%) were due to aseptic loosening, one (1.7 %) due to instability and one (1.7%) because of deep infection. In the C-M group, three elbows required revision (4.8 %), one for periprosthetic fracture (1.6 %) and two for deep infection (3.2 %). The results of survival analysis did not differ between the two groups. DISCUSSION: The weak point of Souter Strathclyde total elbow arthroplasty is the ulnar component whose impairment and subsequent wear are involved in all cases of aseptic loosening. An insufficient length of the humeral component is another risk factor. Even natural movements of the elbow joint produce concentration of stresses on a small surface; this gradually weakens component fixation in bone and results in aseptic loosening. A higher risk of failure in Coonrad-Morrey elbow arthroplasty is associated with polyethylene lining of the hinge mechanism. CONCLUSIONS: The Coonrad-Morrey total elbow replacement is at present considered the method of choice. It is easier to perform and provides better functional outcomes than the Souter-Strathclyde elbow implant. PMID- 22094157 TI - [Treatment of degenerative spondylolisthesis of the lumbosacral spine by decompression and dynamic transpedicular stabilisation]. AB - PURPOSE OF THE STUDY: The aim of the study was to present the effect and advantages of surgical decompression and dynamic transpedicular stabilisation in patients with degenerative spondylolisthesis of the lumbosacral spine. MATERIAL AND METHODS: This prospective study involved patients undergoing dynamic transpedicular stabilisation using Isolock or Isobar TTL (Scient X, France) systems. Between June 2003 and June 2009, 65 patients were treated and followed up. They were aged 35 to 75 years (average, 57.17 years), and there were 32 men and 33 women. Follow-up ranged from 1 to 6 years. Based on indications for surgery they fell into two groups. Group 1 included 52 patients with grade I or II degenerative spondylolisthesis or retrolisthesis. Group 2 (control) consisted of 13 patients with degenerative disc disease or failed back surgery syndrome. The disorder had always been manifested by combined axial and radicular symptoms. Treatment included posterior decompression of nerve structures by laminectomy in conjunction with semi-rigid stabilisation, without fusion. Followup clinical (VAS, ODI), neurological and radiographic examinations were carried out at 6 weeks, 6 months and 1 to 6 years after surgery. The VAS and ODI results of both groups were statistically analysed and compared. RESULTS: During follow-up the ODI values decreased by 54 % (from 58.4 % to 26.8 %) and VAS values by 62 % (from 7.9 to 3.0) as compared with the pre-operative values, and this was statistically significant. When both groups were compared, the VAS values decreased significantly (by 5.61) in Group 1, as compared with Group 2 (decrease by 3.54). DISCUSSION: In the treatment of pseudospondylolisthesis, the semi-rigid stabilisation with spinal decompression, as presented here, is a convenient alternative to simple decompression without fixation or to various forms of instrumented or non-instrumented arthrodesis. A disadvantage associated with arthrodesis is a higher risk of ASD development; dynamic systems do not allow for reduction of spondylolisthesis and involve a change in sagittal spinal balance, and simple decompression carries the risk of slip progression and recurrent problems. CONCLUSIONS: The authors demonstrated that decompression combined with semi-rigid stabilisation had a very good effect on the clinical state of patients with degenerative spondylolisthesis (retrolisthesis) at medium-term follow-up. The procedure was less effective in other indications. Semi-rigid stabilisation with Isobar TTL or Isolock systems prevented the progression of anterolisthesis or retrolisthesis; none of the patients experienced instrumentation failure. Neither symptomatic restenosis nor disc herniation was found in the instrumented segment. Semi-rigid stabilisation can, if necessary, be converted to fusion or disc replacement. PMID- 22094158 TI - [Minimally invasive cervical elastic laminoplasty - principles and surgical technique]. AB - PURPOSE OF THE STUDY: To present a new technique of minimally invasive decompression of the cervical spinal canal using elastic and plastic deformation of the laminae. MATERIAL AND METHODS: Short midline vertical incision provides an access to the superior aspect of the target spinous processes. Cranial edge of the lamina is located by a midline, muscle-sparing interspinous dissection. The spinous process is cut in mid-sagittal plane using a thin blade of an ultrasonic bone scalpel down to epidural space. The created sagittal cleavage of the spinous process is subjected to tension and elastic distraction by a custom-designed distractor (Aesculap, Germany). Gradual increase of the distraction force leads to a significant plastic deformation. This reduces the distraction force and allows for a wider exposure which, in turn, facilitates dural visualization, resection of the yellow ligament and undercutting of approximately a half of the adjacent intact laminae. After completion of decompression, the plastic arch expansion can be maintained either by interposed bone-graft or appropriately shaped cage secured by a circumferential suture to the spinous process. Soft tissue resection and permanent expansion of the laminae provide sufficient decompression of the cervical spinal cord. In multilevel stenosis, the desired laminae can be expanded using this technique. To achieve the same degree of canal expansion as that by a classic laminoplasty (C3-7), a skip technique can be utilized. This involves combining expansive laminoplasty of C4 and C6 with bilateral undercutting of C5 and partial undercutting of C3 and C7. This can be achieved through two short vertical incisions. Based on data and experience gained from testing on 11 cadavers, we applied this method in 7 patients requiring posterior cervical decompression. RESULTS: The spinous process or laminae fractured during expansion in the initial 4 patients and the procedure required conversion to a minimally invasive laminectomy. Further modification of the distractor and spinous process splitting technique resulted in elimination of this complication in subsequent cases. In all remaining patients, sufficient canal expansion was achieved by soft tissue resection and distraction of laminae, typically reaching 5 - 8 mm. Minimally-invasive muscle-sparing midline approach provided very positive functional results in terms of postoperative pain and range of motion allowing for immediate mobilization without external bracing. CONCLUSION: Minimally invasive, muscle sparing, expansive laminoplasty provides adequate spinal canal expansion. Use of this technique and its muscle-sparing nature potentially result in improvement of early functional outcomes when compared to standard laminoplasty techniques requiring lateral lamina-facet border exposure. However, the theoretical superiority of this technique will need to be clinically scrutinized in a well designed surgical outcome study. PMID- 22094159 TI - [Vertebral body augmentation using a vertebral body stent]. AB - PURPOSE OF THE STUDY: Osteoporotic vertebral fractures can be treated by minimally invasive percutaneous vertebral augmentation with bone cement using vertebroplasty or balloon kyphoplasty. Transcutaneous reduction and vertebral body stenting has been the most recent principle. In contrast to balloon placement in kyphoplasty, the stent remains in the vertebral body and supports both the vertebral body and cement filling. In this retrospective study we present the essential information on the method and our first results. MATERIAL AND METHODS: The method of vertebral body stent placement was used in 22 patients treated at 29 levels. Of these, 19 patients with 26 segments followed up for 3 months were evaluated. The group included 12 women and seven men with an average age of 68.3 years (12 to 83). The patients assessed their subjective complaints on the visual analogue scale (VAS) before surgery, and then at 1, 6 and 12 weeks post-operatively. The value of vertebral body reduction was obtained by measurement of anterior, middle and posterior vertebral body heights (AVBH, MVBH and PVBH, respectively) and a change in the vertebral body kyphotic angle (VBKA). RESULTS: Twenty-four vertebrae were treated for osteoporotic fracture and two as preventive stenting in metastatic breast cancer. In 24 fractures, the stents extended fully in 20 vertebrae, i.e., 40 stents. These fractures evidently were not older than 3 months. In four segments, a total of eight stents did not extend at all or did only slightly. The 20 stabilised vertebral bodies had an average AVBH value of 19.41 mm pre-operatively and that of 22.775 mm post-operatively, which is an average increase by 3.365 mm in absolute numbers and by 17.34 %. The average pre- and post-operative MVBH values were 16.625 mm and 23.065 mm, which was improvement by 6.41 mm or by 38.56 %. The average PVBH values pre- and post operatively were 26.835 mm and 28.31 mm, which meant improvement by 1.475 mm or by 5.5 %. The average correction of the kyphotic angle was 4.58 degrees , i.e., 35.2 %, from a VBKA of 11.71 degrees pre-operatively to 7.13 degrees post operatively. There were five cases (22.7 %) of cement leakage, i.e., two of ventral leakage, one of lateral leakage, one of dorsal leakage through a canal left in the pedicle by cannula insertion, and a dorsal leakage in metastatic disease. No neurological findings were recorded. The average VAS scores were as follows: 81.4 before surgery, 30.6 at 1 week, 16.3 at 6 weeks and 15.4 at 12 weeks after surgery. DISCUSSION: Two experimental and one clinical study on vertebral body stenting only have been available in the recent relevant literature. In comparison with their results as well as with those of previous reports on vertebroplasty and kyphoplasty, our results showed high quality fracture reduction in all vertebrae. The rapid decrease in pain intensity in our group is comparable with all available groups treated by any method of vertebral body augmentation by cement injection; and cement leakage was recorded in even fewer cases. CONCLUSIONS: The novel method of vertebral body stenting with cement augmentation provides a rapid pain relief, gives stability to fracture reduction and has a low rate of cement leakage. However, care must be taken not to indicate cases with a damaged posterior corticalis of the vertebral body. PMID- 22094160 TI - [Reduction of radiation exposure by the use of fluoroscopic guidance in transpedicular instrumentation]. AB - PURPOSE OF THE STUDY: The variability in width, height, and orientation of spinal pedicles makes pedicle screw insertion a delicate operation. Fluoroscopic guidance often exposes the patient and especially surgeons to relatively high doses of ionising radiation. The use of pulsed fluoroscopy is safer, as compared to continuous fluoroscopy, because of reduced radiation exposure. There are increasing numbers of literature reports regarding the high doses of radiation to which orthopaedic and spine surgeons are exposed during surgical procedures. Spine surgery can be associated with significant radiation exposure to the surgical staff. The purpose of this prospective study was to compare a computer assisted navigation with a conventional procedure in order to assess if it is possible to reduce radiation exposure while preserving the accuracy of screw placement. MATERIAL AND METHODS: The first "conventional" group consisted of 30 patients, with an average of 1.9 segments of the lumbar spine stabilised. Screws were inserted transpedicularly under image intensifier guidance. In the second "navigated" group of 30 patients, stabilisation of 1,8 segments was performed on average. A CT-free fluoroscopic 2D spinal navigation system (VectorVision, Brain LAB, Germany) was used intra-operatively. It combines image-guided surgery with C arm fluoroscopy. For each surgery (navigated or not), the duration of irradiation was recorded. The irradiation duration was collected from the X-ray image intensifier. In both groups the screw positioning accuracy was controlled intra operatively according to Learch's, Acikbas's, and Whitecloud's methods from AP and lateral images and by meticulous pedicle palpation. RESULTS: The irradiation duration calculated to one vertebra (two screws) was significantly shorter in the second (navigated) group (3.4 s) than in the first (conventional) group (14.4 s). The mean duration of data registration was 6.0 minutes (range, 3 to 11 minutes). The mean ratio according to Acikbas's calculation method was 43.2 % (range, 32 % to 74 %) in the first (conventional) group and 44.1 % (range, 35 % to 76 %) in the second (navigated) group. DISCUSSION: During a conventional surgical procedure many X-ray images are made to control the accuracy of screw insertion. If the trajectory is not satisfying, it must be corrected or the pedicle is drilled again, always with a new fluoroscopic control. The process is repeated until satisfactory orientation is achieved. This is the explanation for a much longer duration of irradiation in conventional procedures. Navigation facilitates the surgical act, enabling us to acquire the right position of all screws, with only an AP image and a lateral image at the beginning of instrumentation for data registration; prolongation of the operative time is irrelevant. CONCLUSIONS: Navigation allows us to keep the same accuracy of pedicle screw placement while reducing radiation exposure of the surgeons and operating room staff by about one quarter. In multiple-level vertebral instrumentations this reduction is more pronounced. In centres where many procedures involving spine instrumentation are done every day, the "saved" exposure time can amount to hours. PMID- 22094161 TI - [Experiences and first outcome of posterior ankle arthroscopy]. AB - PURPOSE OF THE STUDY: Many hind foot problems can be treated by endoscopic procedures. It is essential to identify the best candidates for this treatment and also to assess the risk associated with these surgeries. Here we present our first experience with posterior ankle arthroscopy. MATERIAL AND METHODS: Between September 2007 and September 2009, we performed 21 arthroscopic procedures on the posterior ankle (one-stage combined anterior and posterior surgery, 11x; posterior procedure, 7x; two-stage anterior and posterior surgery, 3x). The group included 21 patients, 18 men and three women, with an average age of 36 years (20 to 64) at the time of surgery. The average follow-up was 27 months (16 to 38). Both posterolateral and posteromedial approaches were used, with major landmarks being the processus posterior tali, posterior talofibular ligament and long flexor tendon of the big toe. Surgery was performed by experienced specialists. Outcome evaluation was based on the AOFAS and Kitaoka clinical rating scales and the complication rate. RESULTS: In our group, the diagnoses treated by arthroscopic surgery were as follows: arthrofibrosis (16x; 76 %), hypertrophic processus posterior tali (13x; 62 %), and loose intra-articular bodies (8x; 38 %). All patients reported improvement in clinical condition after surgery. The differences between the mean pre- and post-operative values were 24 points for the AOFAS score (58 versus 82; p<0.00015) and 23 points for the Kitaoka score (58 versus 81; p < 0.00015). The most effective outcomes were achieved in the patients operated on for loose bodies or hypertrophic processus posterior tali. The worst result was found in the patient with advanced arthritis of the ankle that had to undergo arthrodesis 13 months following arthroscopic treatment. There were eight complications in five patients (24 %), including excessive bleeding in five cases, temporary loss of sensation in two, and a damaged tendon of the long flexor of the big toe. DISCUSSION: Arthroscopic surgery has recently been advocated by many authors. The majority of them have reported good results and an acceptable risk of complications. Almost all use either the posteromedial or the lateral approach, which are anatomically safe procedures. Surgery is followed by a thorough rehabilitation programme that allows most patients to resume their normal daily activities in 8 weeks. Our results were not so good because we mostly treated post-traumatic conditions, with advanced ankle arthritis in several patients. CONCLUSIONS: Arthroscopy is an effective method for treating both intra- and extra-articular pathologies in the posterior ankle. The best effect of treatment was recorded in posterior tibiotalar impingement syndrome or after extraction of loose intra-articular bodies. In advanced ankle arthritis, on the other hand, the use of arthroscopic treatment should be carefully considered. The risk of complications is high and the procedure requires good knowledge of anatomy and high surgical skills. PMID- 22094162 TI - [Lumbo-pelvic stabilisation following subtotal sacrectomy due to a giant invasive schwannoma. Case report]. AB - The case of a rare giant invasive schwannoma of the sacrum is presented. This is a slow-growing tumour reaching a large size because of non-specific symptoms. Even though it is benign in nature, it has characteristics markedly differing from commonly-known neurinomas; it invades and destroys bone, on MR examination it shows a heterogeneous structure reminiscent of a malignant process and its growth around the nerve roots makes nerve dissection in the cauda equina very complicated. At the time of diagnosis a major part of the sacral bone is usually destroyed and nerve root dissection is very difficult. In this case, because of removal of most of the tissue, an almost complete sacrectomy was necessary including the sacral roots with the exception of S1. At the second stage, lumbo pelvic stabilisation was carried out using the modified Galveston technique. Since only a very few similar cases have been reported, it is not possible to predict the post-operative outcome in terms of potential recurrence or residual progression. In our patient a small residuum was stable even at 37 months after surgery. She remained incontinent after surgery, but able to walk unaided. Radiographic examination showed the osteosynthetic material without signs of loosening and in a good position. PMID- 22094163 TI - [Solitary distal femoral osteosarcoma in 89-year-old woman. Case report]. AB - The authors describe the case of an 89-year-old patient with a one-month history of pain in the right knee and a pathological fracture of the distal femur. Excisional biopsy showed a classical osteogenic sarcoma. The patient died after six months of palliative surgical and oncological therapy; her primary disease generalised and progressed with numerous metastases. The authors discuss the possibilities of histological diagnostics of osteogenic sarcoma and its differential diagnosis. They draw attention to a possible occurrence of this type of sarcoma also in elderly patients, and not only in adolescents. PMID- 22094164 TI - [C-sign and talocalcaneal coalition]. AB - Talocalcaneal coalition is an abnormal bridge between talus and calcaneus, causing pain and restriction of subtalar movement; its incidence is less than 1 %. The signs and symptoms usually become manifest in the second decade of life with ossification of the lesion. They involve flat foot, peroneal muscle spasm, tarsal tunnel syndrome, or valgus tilt of the heel. The sings need not be noticeable and may appear only as tiredness and vague pain in the hind foot after exercise or an easily twisted ankle. The authors describe the case of talocalcaneal coalition in a 20-year-old man, incidentally diagnosed at ankle fracture. The presence of C-sign led to CT examination and the exact diagnosis. Radiological demonstration of this abnormality may be difficult because plain X ray images in both projections may show normal findings. Literature data report, in addition to C-sign, further secondary signs of talocalcaneal coalition present on lateral radiographs of the ankle joint. Although these signs do not directly point to talocalcaneal coalition, they reveal abnormal anatomy or movement of the joint and may initiate more thorough examination by CT or MRI and the establishment of an exact diagnosis. Therefore, to know the secondary signs and pay attention to them is very useful. PMID- 22094165 TI - Stress fibers stabilize the position of intranuclear DNA through mechanical connection with the nucleus in vascular smooth muscle cells. AB - Actin stress fibers (SFs) running across the top surface of the nucleus in vascular smooth muscle cells were dissected using laser nano-dissection technique to release its pretension, and the dynamic behavior of SFs, nucleus, and intranuclear DNA were investigated. SFs shortened across the top surface of the nuclei after their dissection. The nuclei moved in the direction of SF retraction, and showed marked local deformation, indicating that SFs firmly connected to the nuclear surface. Intranuclear DNA located near and around the dissected SFs disappeared and their distribution changed markedly. These findings suggest that SFs stabilize the position of intranuclear chromatin through mechanical connection with the nucleus. The tension of SFs may be transmitted mechanically to the nucleus inducing conformational changes of intranuclear chromatin. PMID- 22094166 TI - Human immunodeficiency virus-1 Rev protein activates hepatitis C virus gene expression by directly targeting the HCV 5'-untranslated region. AB - Coinfection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) accelerates hepatitis C disease progression; however, the mechanism underlying this effect is unknown. Here, we investigated the role of HIV-1 in HCV gene expression and the mechanism involved in this regulation. We discovered that HIV-1 Rev protein activates HCV gene expression. We further revealed that Rev binds to the internal loop of the HCV 5'-untranslated region (5'-UTR) to stimulate HCV IRES-mediated translation. PMID- 22094167 TI - The chromophore structure of the long-lived intermediate of the C128T channelrhodopsin-2 variant. AB - The photocycle of the light-activated channel, channelrhodopsin-2 C128T, has been studied by resonance Raman (RR) spectroscopy focussing on the intermediates P380 and P353 that constitute a side pathway in the recovery of the parent state. The P353 species displays a UV-vis absorption spectrum with a fine-structure reminiscent of the reduced-retro form of bacteriorhodopsin, whereas the respective RR spectra differ substantially. Instead, the RR spectra of the P380/P353 intermediate couple are closely related to that of a free retinal in the all-trans configuration. These findings imply that the parent state recovery via P380/P353 involves the transient hydrolysis and re-formation of the retinal protein linkage. PMID- 22094168 TI - Parent, sibling and peer influences on smoking initiation, regular smoking and nicotine dependence. Results from a genetically informative design. AB - We sought to determine whether parenting, sibling and peer influences are associated with offspring ever smoking, regular smoking and nicotine dependence (ND) after controlling for familial factors. We used a twin-family design and data from structured diagnostic surveys of 1919 biological offspring (ages 12-32 years), 1107 twin fathers, and 1023 mothers. Offspring were classified into one of four familial risk groups based on twin fathers' and their co-twins' history of DSM-III-R nicotine dependence. Multivariate multinomial logistic regression was used to model familial risk, paternal and maternal parenting behavior and substance use, sibling substance use, and friend and school peer smoking, alcohol and drug use. Ever smoking was associated with increasing offspring age, white race, high maternal pressure to succeed in school, sibling drug use, and friend smoking, alcohol and drug use. Offspring regular smoking was associated with these same factors with additional contribution from maternal ND. Offspring ND was associated with increasing offspring age, male gender, biological parents divorce, high genetic risk from father and mother ND, maternal problem drinking, maternal rule inconsistency and sibling drug use, and friend smoking, alcohol and drug use. Friend smoking had the largest magnitude of association with offspring smoking. This effect remains after accounting for familial liability and numerous parent and sibling level effects. Smoking interventions may have greatest impact by targeting smoking prevention among peer groups in adolescent and young adult populations. PMID- 22094169 TI - Do drinking motives mediate the association between sexual assault and problem drinking? AB - Sexual assault and problem drinking are both prevalent in college women and are interrelated. Findings from cross-sectional research indicate that motives to drink to decrease negative affect (coping motives) or to increase positive affect (enhancement motives) are partial mediators of the sexual assault-problem drinking relation. However, no published longitudinal studies have examined these relations. The current study tests a longitudinal model and examines coping and enhancement motives as potential mediators. Participants were 131 female undergraduates who completed baseline measures of self-reported sexual assault victimization and problem drinking. Coping and enhancement motives were measured at three-month follow up; problem drinking was measured at six-month follow-up. Analyses using structural equation modeling (SEM) indicated direct and indirect paths in the sexual assault-problem drinking relation. Zero-order correlations indicated significant, positive relations among drinking motives, sexual assault, and drinking variables. Longitudinally, mediation was evident for coping but not enhancement motives. Ultimately, findings were most consistent with self medication hypotheses about the sexual assault - problem drinking relation - i.e., drinking in order to gain relief from symptoms or problems. PMID- 22094170 TI - Cocaine and its metabolites in the placenta: a systematic review of the literature. AB - It is clear that cocaine and cocaine metabolites are present in the placenta and may harm the fetus. The results of the experimental manipulation of cocaine exposure are not reported in the literature in a consistent manner. We conducted a systematic review of selected articles that demonstrated the analytical detection of cocaine and its metabolites in the placenta and that were published from January 1, 1956-June 30, 2011 using Medline, Toxline and Scopus databases. The collected data confirm that the placenta does not act as a barrier to fetal exposure, that cocaine quickly crosses the placenta and that one of the essential roles of the placenta is to metabolize cocaine during pregnancy. Our systematic review summarized the results showing that cocaine, benzoylecgonine and norcocaine are stored in the myometrium and the placental membrane and maintain continuous drug delivery to the amniotic fluid (and to the fetus) probably via diffusion. PMID- 22094171 TI - Community and household socioeconomic factors associated with pesticide-using, small farm household members' health: a multi-level, longitudinal analysis. AB - BACKGROUND: Longitudinal studies using multi-level models to examine health inequalities in lower and middle income countries (LMICs) are rare. We explored socio-economic gradients in health among small farm members participating in a pesticide-related health and agriculture program in highland Ecuador. METHODS: We profiled 24 communities through key informant interviews, secondary data (percent of population with unsatisfied basic needs), and intervention implementation indicators. Pre (2005) and post (2007) surveys of the primary household and crop managers included common questions (education, age, and the health outcome - digit span scaled 0-10)) and pesticide-related practice questions specific to each. Household assets and pesticide use variables were shared across managers. We constructed multi-level models predicting 2007 digit span for each manager type, with staged introduction of predictor variables. RESULTS: 376 household managers (79% of 2005 participants) and 380 crop managers (76% of 2005 participants) had complete data for analysis. The most important predictor of 2007 digit span was 2005 digit span: beta (Standard Error) of 0.31(0.05) per unit for household and 0.17(0.04) for crop managers. Household asset score was next most important: 0.14(0.06) per unit for household and 0.14(0.05) for crop managers. Community percent with unsatisfied basic needs was associated with reductions in 2007 digit span: -0.04(0.01) per percent for household and 0.03(0.01) for crop managers. CONCLUSIONS: The important roles of life endowments and/or persistent neurotoxicity were exemplified by limited change in the health outcome. Gradients by household assets and community deprivation were indicative of ongoing, structural inequities within this LMIC. PMID- 22094172 TI - Virus-induced acute respiratory distress syndrome: epidemiology, management and outcome. AB - The acute respiratory distress syndrome (ARDS) can be induced by viral diseases, with two virus types being responsible: respiratory viruses that cause community acquired viral pneumonia and Herpesviridae that cause nosocomial viral pneumonia. Among the respiratory viruses that can affect the lung and cause ARDS, pandemic viruses head the list, with influenza viruses H5N1 and H1N1 2009 being the most recently identified. However, other viruses can cause severe ARDS. Notably, a novel coronavirus was responsible for the severe acute respiratory syndrome outbreak in 2003. Apart from these pandemic viruses, respiratory viruses are rarely responsible for viral pneumonia and ARDS. Other than antiviral drug (mainly oseltamivir) administration and avoidance of corticosteroids, management of ARDS due to these viruses does not differ from that for ARDS caused by other diseases. Among Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) are the two viruses causing nosocomial viral pneumonia that can evolve into ARDS. HSV is frequently recovered in the respiratory tract of mechanically ventilated patients and can sometimes be responsible for HSV bronchopneumonitis. Although not evaluated for this indication, acyclovir can be a therapeutic option for patients with HSV bronchopneumonitis and ARDS. CMV pneumonia can also occur in mechanically ventilated patients, but is difficult to diagnose because virus recovery does not necessarily mean viral disease. Ganciclovir can be considered for patients with ARDS and histology- or cytology-proven CMV pneumonia. PMID- 22094173 TI - [Publication of MD theses at Brest University Medical School: current situation and courses of action]. PMID- 22094174 TI - Coordinated multidisciplinary care for ambulatory Huntington's disease patients. Evaluation of 18 months of implementation. AB - BACKGROUND: A multidisciplinary outpatient department was set up in the northern part of the Netherlands because of a local lack of adequate treatment and care for Huntington's disease (HD)patients. Outreaching multidisciplinary care is a novel way to optimise functioning and quality of life of HD patients. The vast majority of patients want to stay home as long as possible. Huntington's disease is a devastating neurodegenerative disorder leading to complete disability and long term residence in a specialised institution. In this paper we outline this new type of treatment and give the results of 1.5 year, we also present the results of an inquiry on the appreciation of the working method. METHODS: In the first project half (1.5 yr) 28 patients were seen as had been anticipated. The multidisciplinary team consisting of an institutional physician, a psychologist, a speech and language therapist, a social worker, an occupational therapist and a case manager, assesses the stage of the disease and formulates, coordinates and implements the individual care and treatment plan in the home situation. After 1.5 year a questionnaire on the appreciation of the department was sent to patients, caregivers, healthcare professionals, the lay organisation and Dutch "experts in the field". RESULTS: For the 28 HD patients a total of 242 problems and actions were verbalised in the care plan, which was accepted by the majority of the patients. Especially informal caregivers, the lay organisation and the Dutch "experts in the field" were enthusiastic on the outreaching and multidisciplinary nature of the department. The verdict over the continuance of the clinic was positive and unanimous. CONCLUSIONS: We concluded that coordinating outreaching multidisciplinary care from an outpatient clinic into the dwelling place of the patient is feasible and appreciated. PMID- 22094175 TI - [Neurotization of the deep branch of ulnar nerve with anterior interosseous nerve: anatomic study]. AB - INTRODUCTION: The paralysis of the deep branch of ulnar nerve has major consequences on the motricity of the hand that will be felt as more handicapping by the patient than the sensory deficit. The current treatment of ulnar nerve lesions is suture or nerve graft in first intention and is essentially palliative in case of failure. We were interested in the anatomy of the anterior interosseous nerve and the deep branch of ulnar nerve to know if neurotization using direct suture of these two branches was possible in every case. PATIENTS AND METHODS: Our anatomical study was done on 15 upper limbs. We dissected the branch of the anterior interosseous nerve innervating the pronator quadratus muscle and performed an intraneural dissection of the deep branch of ulnar nerve. The distance between these two branches was then measured. RESULTS: The mean distance separating the deep branch of ulnar nerve and the anterior interosseous nerve is 2.5mm (-10-10). The direct suture of these two branches is possible in every case of this study. The macroscopic calibre of both branches is similar. DISCUSSION: Our study shows that the neurotization of the deep branch of ulnar nerve with the anterior interosseous nerve is possible in every case using direct suture, the wrist can be immobilised temporarily in flexion to reduce the tension. Ustun et al. as well as Wang and Zhu showed that their calibre and the number of axons is similar. We think that neurotization of the deep branch of ulnar nerve with the anterior interosseous nerve can be realized in first intention in case of high lesion of ulnar nerve. There is no major functional loss due to the paralysis of the pronator quadratus muscle. CONCLUSION: Neurotization of the deep branch of ulnar nerve with the anterior interosseous nerve has no major functional loss and gives possible recovery of all the intrinsic muscles innervated by the deep branch of ulnar nerve. This neurotisation can be considered as an alternative to the usual techniques of direct suture or nerve graft, in case of lesion above mid forearm. PMID- 22094176 TI - [A bilateral and symmetric anatomic variation of a lombrical muscle causing a trigger finger]. AB - Trigger finger is a very common disease. The vast majority of trigger fingers are primary idiopathic trigger fingers. We report the case of a bilateral and symmetric triggering of the fifth finger secondary to an anatomical variation of the lumbrical muscle. This lumbrical muscle arose from the flexor digitorum superficialis instead of the flexor digitorum profundus as is usual. To our knowledge, this is the third published case of trigger finger caused by an anatomical abnormality of a lumbrical muscle. PMID- 22094177 TI - [Techniques of peripheral nerves repair: evolution of the literature from 1950 to 2010]. AB - The life expectancy of technological innovations is estimated at 50years. In medicine, these cycles were poorly studied. The purpose of this work was to study the time-evolution of publications concerning the techniques of repair of the peripheral nerves (TRPN). We listed the publications concerning TRPN since their appearance in the medical literature until nowadays, then studied their evolution in the time. We looked in "Medline((r))" for the publications on TRPN between 1950 and 2010. The direct techniques were published 156 times. The sutures and the biological glue appear in 1966 and the laser in 1979. The indirect techniques were published 199 times. The nerve guides appear in 1956, the vein grafts in 1965, the nerve grafts in 1977. In the decade 2000-2010, the literature produced as many publications on TRPN (181) as in the half-century from 1950 to 2000 (174). Conversely, the global medical literature produced twice as few publications in the decade 2000-2010 (7000000) than in the half-century 1950-2000 (13000000). Several hypotheses can be evoked: encouragement of scientific publication, the development of functional surgery, the augmentation of microsurgery education. PMID- 22094178 TI - The "peg test": a novel technique for dexterity evaluation in hand immobilized with a splint. AB - Manual dexterity tests are difficult to apply in the clinical practice. They are either destined for specific lesions, or are rather complicated and time consuming. The aim of this study was to evaluate a new manual dexterity test for hand immobilized with a splint: the "peg test". Our series included 86 persons (without any hand trauma or disease) of mean age 42 years of which 77 were right handed. Materials included five pegs, splints immobilizing the DIP joint, a desk and a stopwatch. Each subject moved the pegs from a horizontal to a vertical position using the thumb-ring pinch grip. This was repeated three times without a splint, with a palmar splint, with a simple dorsal splint and with a dorsal splint glued to the nail, then once more without a splint. A time score was recorded for each trial. A point was deduced at each fall of a peg for result analysis. Results showed that a learning curve affected performance, but that dominance and age before learning had no effect. After learning performance diminished with these variables in the following order: without splint, then more so with a glued splint, even more with a simple dorsal splint and most with a palmar one. The peg test fulfills metrological requirements of dexterity tests: test-retest (intra-observer) reliability (reproducibility), inter-observer reliability (both measured by correlation coefficient), and validity of instrument of measurement. Simple, rapid and reliable, it is perfectly adapted to manual dexterity evaluation in hand immobilized with a splint. PMID- 22094179 TI - Use of a common laboratory glassware detergent improves recovery of Cryptosporidium parvum and Cyclospora cayetanensis from lettuce, herbs and raspberries. AB - The success of any protocol designed to detect parasitic protozoa on produce must begin with an efficient initial wash step. Cryptosporidium parvum and Cyclospora cayetanensis oocysts were seeded onto herbs, lettuces and raspberries, eluted with one of four wash solutions and the recovered number of oocysts determined via fluorescent microscopy. Recovery rates for fluorescein thiosemicarbazide labeled C. parvum oocysts seeded onto spinach and raspberries and washed with de ionized water were 38.4 +/- 10.1% and 34.9 +/- 6.2%, respectively. Two alternative wash solutions viz. 1M glycine, pH 5.5 and a detachment solution were tested also using labeled C. parvum seeded spinach and raspberries. No statistically significant difference was noted in the recovery rates. However, a wash solution containing 0.1% Alconox, a laboratory glassware detergent, resulted in a significant improvement in oocyst recovery. 72.6 +/- 6.6% C. parvum oocysts were recovered from basil when washed with 0.1% Alconox compared to 47.9 +/- 5.8% using detachment solution. Also, C. cayetanensis oocysts were seeded onto lettuces, herbs and raspberries and the recovery using de-ionized water were compared to 0.1% Alconox wash: basil 17.5 +/- 5.0% to 76.1 +/- 14.0%, lollo rosso lettuce 38.3 +/- 5.5% to 72.5 +/- 8.1%, Tango leaf lettuce 45.9 +/- 5.4% to 71.1 +/- 7.8% and spring mix (mesclun) 39.8 +/- 0.7% to 80.2 +/- 11.3%, respectively. These results suggest that the use of Alconox in a wash solution significantly improves recovery resulting in the detection of these parasitic protozoa on high risk foods. PMID- 22094180 TI - Diversity of the heterotrophic microbial populations for distinguishing natural mineral waters. AB - In the recent years the consumption of natural mineral waters has risen all over the world, becoming a usual alternative for tap water and other beverages. Natural mineral waters are complex environments containing a high diversity of autochthonous microbiota. The identification and characterization of this indigenous microbiota may help to detect changes occurring in the different steps of the bottling process and take preventive measures before the bottled water arrives to the consumer. The aims of this study were to describe the bacterial heterotrophic populations in natural mineral waters with a cultivation-dependent method and determine whether their autochthonous microbiota were specific enough to be clearly distinguished from that of other natural mineral waters with a phenotypic-based method. For this purpose, water from three independent Spanish springs was sampled in two seasons (winter and summer) and heterotrophic aerobic bacterial strains were isolated at two temperatures (22 +/- 2 degrees C and 36 +/ 2 degrees C) on R2A agar. Isolates were phenotyped biochemically with Php-48 plates (Bactus AB, Sweden), and the indexes of diversity and similarity between populations were calculated. The 16S rRNA gene of the most representative strains of each biochemical cluster was sequenced for its identification. Finally, a ten fold cross-validation method was assayed for the identification of the origin of a natural mineral water when phenotyping a set of isolates. High levels of diversity were found at all sites. One of the sources was found to present less diversity due to a confirmed contamination with Pseudomonas aeruginosa. The study of the similarities showed that growing temperatures and seasons caused significant differences in structures and composition at the sources. In addition, several bacterial species were isolated and identified, some of them rarely isolated in natural mineral waters, revealing the complexity and lack of knowledge of these ecosystems. Consequently, the applied phenotypic methodology was found to be feasible for differential identification of microbiota in these environments. Moreover, the experimental model assayed was strong enough to identify the origin of a natural mineral water. It may thus be possible to confirm that the evaluation of diversity of heterotrophic aerobic bacterial populations could be applied to identify bottled water sources. PMID- 22094181 TI - Virulence factors and genetic variability of Staphylococcus aureus strains isolated from raw sheep's milk cheese. AB - Contamination of dairy products with Staphylococcus aureus can be of animal or human origin. The host pathogen relationship is an important factor determining genetic polymorphism of the strains and their potential virulence. The aim of the present study was to carry out an extensive characterization of virulence factors and to study the genetic variability of S. aureus strains isolated from raw ewe's milk cheese. A total of 100 S. aureus strains isolated from cheese samples produced in 10 artisan cheese factories were analyzed for the presence of enterotoxins (sea-see) and enterotoxins-like genes (seh, sek, sel, sem, seo, sep), leukocidins, exfoliatins, haemolysins, toxic shock syndrome toxin 1 (TSST 1) and the accessory gene regulator alleles (agr). Strains were also typed using pulsed-field gel electrophoresis (PFGE). AMOVA analysis carried out on PFGE and PCR data showed that the major component explaining genetic distance between strains was the dairy of origin. Of the total isolates 81% had a pathogenicity profile ascribable to "animal" biovar while 16% could be related to "human" biovar. The biovar allowed to estimate the most likely origin of the contamination. Minimum inhibitory concentrations (MICs) of nine antimicrobial agents and the presence of the corresponding genes coding for antibiotic resistance was also investigated. 18 strains carrying blaZ gene showed resistance to ampicillin and penicillin and 6 strains carrying tetM gene were resistant to tetracycline. The presence of mecA gene and methicillin resistance, typical of strains of human origin, was never detected. The results obtained in the present study confirm that S. aureus contamination in artisan cheese production is mainly of animal origin. PMID- 22094182 TI - Parental and child fruit consumption in the context of general parenting, parental education and ethnic background. AB - This study examines the association between parental and child fruit consumption in the context of general parenting, parental education and ethnic background. A cross-sectional study was performed among 1762 parent-child dyads. Mean age of the children was 8 years. One parent completed a questionnaire to measure their own and their child's fruit consumption, parenting style, education level and ethnicity. In mediation and moderation analyses, child fruit consumption was regressed on parental fruit consumption, parenting style, parental education and ethnicity. Participating children consumed on average 7.5 pieces of fruit per week. Fourteen percent met the recommended Dutch norm of two pieces of fruit per day. Parental and child fruit consumption were positively associated. The association was more pronounced under higher levels of psychological control and behavioural control, and among ethnic groups. Additionally, parental education and child fruit consumption were positively associated. Parental fruit consumption partially mediated this association. Interventions are needed to increase child fruit consumption. Interventions should focus on increasing parental fruit consumption and positive parental modelling, with particular focus on low-SES families. Additionally, interventions that combine positive modelling with positive general parenting skills (e.g. increasing behavioural control) may be more effective than interventions that focus on parental modelling alone. PMID- 22094183 TI - Pancreatic dual-source dual-energy CT: is it time to discard unenhanced imaging? AB - AIM: To compare pancreatic virtual unenhanced (VUE) and true unenhanced (TUE) images and to calculate the potential dose reduction by omitting the conventional unenhanced scan. MATERIALS AND METHODS: Fifty-one patients with known or suspected pancreatic masses underwent contrast-enhanced computed-tomography (CT) during unenhanced and portal venous phases acquired in single-energy (SE) mode, and pancreatic parenchymal phase acquired in dual-energy (DE) mode. The image quality (IQ) and image noise (IN) of TUE and VUE images were evaluated. The effective dose of a combined DE/SE dual-phase protocol was compared with that of a theoretical standard SE triple-phase protocol. The results were tested for statistical significance using the Cohen's k, the Wilcoxon's signed rank test, and the paired t-test; p-values of less than 0.05 were considered significant. RESULTS: Mean TUE and VUE IQ were 1.5 +/- 0.6 and 1.6 +/- 0.6 (k = 0.891), with no significant difference (p > 0.05). Mean TUE and VUE IN were 12.3 +/- 1.6 and 10.3 +/- 1.5 HU, and resulted significantly different (p < 0.001). Mean effective doses for a combined DE/SE dual-phase protocol and SE triple-phase protocol were 8.9 +/- 2.4 mSv (range 4.8-16.2 mSv) and 12.1 +/- 3.1 mSv (range 6.4-21.1 mSv). The calculated mean dose reduction achievable by omitting the unenhanced scan was 26.7 +/- 9.7% (range 10-46.1; p < 0.001). CONCLUSION: VUE images are feasible for pancreatic abdominal CT. A combined DE/SE dual-phase protocol permits a significant reduction in dose exposure to patients. PMID- 22094184 TI - Extra-pulmonary manifestations of sarcoidosis. AB - Although, the diagnosis and evaluation of sarcoidosis has traditionally remained confined to the chest, its multi-system nature has been widely recognized. Radiological features of pulmonary sarcoidosis are well known but extra-pulmonary manifestations can produce a plethora of non-specific imaging findings that can affect subcutaneous tissue, and the neurological, cardiac, gastrointestinal, urological, liver, spleen, and skeletal systems. In the literature, there are various case reports and specific system reviews but there are few reviews that encompass all the extra-pulmonary manifestations. In this paper, we comprehensively review the imaging features of extra-pulmonary sarcoidosis with characteristic features as well as atypical presentations. In addition, we discuss the emerging role of nuclear medicine in sarcoidosis. PMID- 22094185 TI - Thrombotic thrombocytopenic purpura triggered by influenza A virus subtype H1N1 infection. AB - We report a case of acquired thrombotic thrombocytopenic purpura (TTP) triggered by influenza A virus subtype H1N1 infection. In December 2010, a 27-year-old man was diagnosed with pneumonia from influenza A virus infection at a local clinic. Two days later, he was admitted to our hospital because of a worsening condition and unexplained thrombocytopenia. The influenza A virus subtype H1N1 real-time polymerase chain reaction test was positive. The patient had typical clinical signs of TTP, thus he was diagnosed with TTP. He received treatment with oseltamivir and high dose methylprednisolone. Plasma exchange therapy was started daily at a 1.5 dose volume of his whole blood. After the 17th plasma exchange therapy, the symptoms and abnormal laboratory results had recovered to normal. Finally, 47 days after admission, the patient had recovered completely and was discharged. This case suggests that the influenza A virus subtype H1N1 infection may have triggered acquired TTP. PMID- 22094186 TI - Myostatin inhibits brown adipocyte differentiation via regulation of Smad3 mediated beta-catenin stabilization. AB - Brown adipocytes play an important role in regulating energy balance, and there is a good correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism of white adipocyte differentiation has been well characterized, brown adipogenesis has not been studied extensively. Moreover, extracellular factors that regulate brown adipogenic differentiation are not fully understood. Here, we assessed the mechanism of the regulatory action of myostatin in brown adipogenic differentiation using primary brown preadipocytes. Our results clearly showed that differentiation of brown adipocytes was significantly inhibited by myostatin treatment. In addition, myostatin-induced suppression of brown adipogenesis was observed during the early phase of differentiation. Myostatin induced the phosphorylation of Smad3, which led to increased beta-catenin stabilization. These effects were blocked by treatment with a Smad3 inhibitor. Expression of brown adipocyte-related genes, such as PPAR gamma, UCP-1, PGC-1alpha, and PRDM16, were dramatically down-regulated by treatment with myostatin, and further down-regulated by co-treatment with a beta catenin activator. Taken together, the present study demonstrated that myostatin is a potent negative regulator of brown adipogenic differentiation by modulation of Smad3-induced beta-catenin stabilization. Our findings suggest that myostatin could be used as an extracellular factor in the control of brown adipocyte differentiation. PMID- 22094187 TI - A comparison of glycine- and ivermectin-mediated conformational changes in the glycine receptor ligand-binding domain. AB - Glycine receptor chloride channels are Cys-loop receptor proteins that isomerize between a low affinity closed state and a high affinity ion-conducting state. There is currently much interest in understanding the mechanisms that link affinity changes with conductance changes. This essentially involves an agonist binding in the glycine receptor ligand-binding site initiating local conformational changes that propagate in a wave towards the channel gate. However, it has proved difficult to convincingly distinguish those agonist induced domain movements that are critical for triggering activation from those that are simply local deformations to accommodate ligands in the site. We employed voltage-clamp fluorometry to compare conformational changes in the ligand-binding site in response to activation by glycine, which binds locally, and ivermectin, which binds in the transmembrane domain. We reasoned that ivermectin-mediated activation should initiate a conformational wave that propagates from the pore-lining domain towards the ligand-binding domain, eliciting conformational changes in those extracellular domains that are allosterically linked to the gate. We found that ivermectin indeed elicited conformational changes in ligand-binding domain loops C, D and F. This implies that conformational changes in these domains are important for activation. This result also provides a mechanism to explain how ivermectin potentiates glycine induced channel activation. PMID- 22094188 TI - Four-and-a-half-LIM protein 1 down-regulates estrogen receptor alpha activity through repression of AKT phosphorylation in human breast cancer cell. AB - The Four-and-a-half LIM protein 1 (FHL-1) is a member of LIM-only protein family. It plays important roles in proliferation and apoptosis regulation of certain hepatocellular carcinoma and human breast cancer. Estrogen receptor alpha (ERalpha) is involved in the development and progression of human breast cancer. IGF/PI3K/AKT signaling pathway also plays certain roles in the program and regulation of human breast cancer and ovary cancer. However, the biological function of FHL-1 in regulation of human breast cancer and in the cross-talk of estrogen and IGF signaling pathway remains largely unknown. In this paper, we show that FHL-1 protein interacts with ERalpha and AKT. FHL-1 represses the translation and transcription of estrogen receptor-responsive genes through down regulating AKT activation. In addition, FHL-1 is not only an ERalpha-interacting co-regulation protein, but also decreases the phosphorylation of AKT and ERalpha. Depression of endogenous FHL-1 by FHL-1 targeted small interfering RNA enhances the expression of these proteins and phosphorylation of AKT and ERalpha. These data suggest that FHL-1 may regulate ER signaling function through regulation of AKT activation besides the physical and functional interaction with ERalpha. By establishing a linkage role of the FHL-1 between the estrogen ERalpha signaling pathway and IGF/PI3K/AKT signaling pathway, this study identifies that FHL-1 proteins may be a useful molecular target for human breast cancer therapy. PMID- 22094189 TI - Chronic widespread pain or fibromyalgia? That is the question. PMID- 22094190 TI - Chronic widespread pain: from peripheral to central evolution. AB - Chronic pain can be classified as localised, regional or widespread, and its high prevalence in the general population seems to increase with age. The majority of cases present with musculoskeletal pain. The conditions associated with chronic widespread pain (CWP) are highly burdensome as their characteristic symptoms may include multifocal pain, fatigue, insomnia, memory difficulties and a higher rate of concomitant mood disorders. After many years of debate, it is still unclear whether CWP (central sensitisation) is an entirely explainable neurotransmitter related process or is partially or totally due to individual cognitive experiences and evaluations. The two models (neurochemical and biopsychosocial) also affect our ability to find therapeutic answers. PMID- 22094191 TI - Central pain mechanisms in chronic pain states--maybe it is all in their head. AB - Mechanisms underlying chronic pain differ from those underlying acute pain. In chronic pain states, central nervous system (CNS) factors appear to play particularly prominent roles. In the absence of anatomical causes of persistent pain, medical sub-specialities have historically applied wide-ranging labels (e.g., fibromyalgia (FM), irritable bowel syndrome, interstitial cystitis and somatisation) for what now is emerging as a single common set of CNS processes. The hallmark of these 'centrally driven' pain conditions is a diffuse hyperalgesic state identifiable using experimental sensory testing, and corroborated by functional neuroimaging. The characteristic symptoms of these central pain conditions include multifocal pain, fatigue, insomnia, memory difficulties and a higher rate of co-morbid mood disorders. In contrast to acute and peripheral pain states that are responsive to non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, central pain conditions respond best to CNS neuromodulating agents, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. PMID- 22094193 TI - Chronic widespread pain in the spectrum of rheumatological diseases. AB - Fibromyalgia (FM) is a rheumatic disease characterised by musculoskeletal pain, chronic diffuse tension and/or stiffness in joints and muscles, fatigue, sleep and emotional disturbances and pressure pain sensitivity in at least 11 of 18 tender points. There are currently no instrumental tests or specific diagnostic markers, and the characteristic symptoms of the disease overlap those of many other conditions classified in a different manner. FM is often associated with other diseases that act as confounding and aggravating factors, including primary Sjogren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It has been reported to coexist in 25% of patients with RA, 30% of patients with SLE and 50% of patients with pSS. Its clinical diagnosis is not easy because FM-like symptoms are frequent, and its differential diagnosis with other causes of chronic diffuse pain is difficult. This is even more true in the case of patients who are positive for antinuclear antibodies (ANAs) because, although sensitive, ANA positivity is not specific for SLE or connective tissue diseases, and can also be found in 10-15% of FM patients. Furthermore, composite indices such as the disease activity score (DAS)-28, which are widely used in everyday clinical practice and clinical trials, may be insufficient to evaluate real inflammatory activity in patients with RA associated with chronic pain syndromes such as FM, and can lead to an overestimate of disease activity in RA. The presence of diffuse pain in autoimmune rheumatic diseases compromises the quality of life of the patients, although overall mortality is not increased. A misdiagnosis harms the patients and the community. Rheumatologists should be able to recognise and distinguish primary and secondary FM, and need new guidelines and instruments to avoid making mistakes. PMID- 22094192 TI - Peripheral pain mechanisms in chronic widespread pain. AB - Clinical symptoms of chronic widespread pain (CWP) conditions like fibromyalgia (FM), include pain, stiffness, subjective weakness, and muscle fatigue. Muscle pain in CWP is usually described as fluctuating and often associated with local or generalised tenderness (hyperalgesia and/or allodynia). This tenderness related to muscle pain depends on increased peripheral and/or central nervous system responsiveness to peripheral stimuli, which can be either noxious (hyperalgesia) or non-noxious (allodynia). For example, patients with muscle hyperalgesia will rate painful muscle stimuli higher than normal controls, whereas patients with allodynia may perceive light touch as painful, something that a 'normal' individual will never describe as painful. The pathogenesis of such peripheral and/or central nervous system changes in CWP is unclear, but peripheral soft tissue changes have been implicated. Indirect evidence from interventions that attenuate tonic peripheral nociceptive impulses in patients with CWP syndromes like FM suggest that overall FM pain is dependent on peripheral input. More importantly, allodynia and hyperalgesia can be improved or abolished by removal of peripheral impulse input. Another potential mechanism for CWP pain is central disinhibition. However, this pain mechanism also depends on tonic impulse input, even if only inadequately inhibited. Thus, a promising approach to understanding CWP is to determine whether abnormal activity of receptors in deep tissues is fundamental to the development and maintenance of this chronic pain disorder. CONCLUSIONS: Most CWP patients present with focal tissue abnormalities including myofascial trigger points, ligamentous trigger points or osteoarthritis of the joints and spine. While not predictive for the development of CWP, these changes nevertheless represent important pain generators that may initiate or perpetuate chronic pain. Local chemical mediators, including lactic acid, adenosine triphosphate (ATP) and cytokines, seem to play an important role in sensitising deep tissue nociceptors of CWP patients. Thus, the combination of peripheral impulse input and increased central pain sensitivity may be responsible for widespread chronic pain disorders including FM. PMID- 22094194 TI - Epidemiology of chronic musculoskeletal pain. AB - Chronic widespread pain (CWP) due to musculoskeletal conditions is a major social burden. The case definition of CWP relies on pain, chronicity (more than 3 months' duration) and widespread distribution (both sides of the body including the axial skeleton). Health Interview Survey (HIS) and Health Examination Survey (HES) have been used to assess the frequency of CWP in the general population. Unfortunately, both techniques are poorly standardised, which hampers comparison of data pertaining to different populations and countries. A major effort in the European Union (EU) is the development of common strategies to investigate musculoskeletal pain through HIS. Issues to be addressed include: (1) loss of daily life functions due to pain; (2) pain duration and rhythm; (3) affected sites; and (4) type of pain. We know that musculoskeletal pain affects between 13.5% and 47% of the general population, with CWP prevalence varying between 11.4% and 24%. Risk factors for musculoskeletal pain include age, gender, smoking, low education, low physical activity, poor social interaction, low family income, depression, anxiety and sleep disorders, as well as performing manual work, being a recent immigrant, non-Caucasian and widowed, separated or divorced. PMID- 22094195 TI - Myofascial pain syndromes and their evaluation. AB - This article reviews the available published knowledge about the diagnosis, pathophysiology and treatment of myofascial pain syndromes from trigger points. Furthermore, epidemiologic data and clinical characteristics of these syndromes are described, including a detailed account of sensory changes that occur at both painful and nonpainful sites and their utility for diagnosis and differential diagnosis; the identification/diagnostic criteria available so far are critically reviewed. The key role played by myofascial trigger points as activating factors of pain symptoms in other algogenic conditions--headache, fibromyalgia and visceral disease--is also addressed. Current hypotheses on the pathophysiology of myofascial pain syndromes are presented, including mechanisms of formation and persistence of primary and secondary trigger points as well as mechanisms beyond referred pain and hyperalgesia from trigger points. Conventional and most recent therapeutic options for these syndromes are described, and their validity is discussed on the basis of results from clinical controlled studies. PMID- 22094196 TI - Trauma and work-related pain syndromes: risk factors, clinical picture, insurance and law interventions. AB - In the past decade, major progress has been made in our understanding of fibromyalgia syndrome (FMS). Various triggers have been implicated as contributing to symptom development in FMS when genetically susceptible individuals are challenged. A substantial amount of data points towards the association between trauma and chronic widespread pain/fibromyalgia syndrome (CWP/FMS). There is abundant data suggesting that the pathogenesis of CWP/FMS might be related to cervical spine injury. Furthermore, several persistent local pain conditions may progress to CWP/FMS. These conditions may share a common pathogenic mechanism namely, central sensitisation. Physical trauma and emotional trauma co-exist in many traumatic events and may interact in the pathogenesis of CWP/FMS. PMID- 22094197 TI - Translational musculoskeletal pain research. AB - Diagnosis and management of musculoskeletal pain is a major clinical challenge. Fundamental knowledge of nociception from deep somatic structures and related mechanisms of sensitisation have been characterised in animals but the translation into clinical sciences is still lacking. Development and refinement of mechanism-based quantitative sensory testing in healthy volunteers and pain patients have provided new opportunities to assess pain and hyperalgesic reactions. The current technologies can provide information about, for example, peripheral and central sensitisation, descending pain control, central integration and structure specific sensitisation. Such a mechanistic approach can be used for differentiated diagnosis and for target validating new and existing analgesics. Mechanistic pain assessment of new compounds under development provides opportunities for target validation in proof-of-concept studies, which generate information to be used for selecting the most optimal patients for later clinical trials. New safe and efficient compounds are highly needed in the area of musculoskeletal pain management. PMID- 22094198 TI - Fibromyalgia and sleep. AB - Chronic pain in fibromyalgia patients, together with its associated symptoms and co-morbidities, is now considered a result of dysregulated mechanisms in the central nervous system (CNS). As fibromyalgia patients often report sleep problems, the physiological processes that normally regulate sleep may be disturbed and overlap with other CNS dysfunctions. Although the mechanisms potentially linking chronic widespread pain, sleep alterations and mood disorders have not yet been proven, polysomnography findings in patients with fibromyalgia and non-restorative sleep and their relationships with clinical symptoms support the hypothesis of a conceptual common mechanism called 'central sensitisation'. Food and Drug Administration (FDA)-approved drugs for the treatment of fibromyalgia may benefit sleep, but their label does not include the treatment of fibromyalgia-associated sleep disorders. Non-pharmacological therapies (including a thorough sleep assessment) can be considered in the first-line treatment of non restorative sleep, although they have not yet been fully investigated in patients with fibromyalgia. Both pharmacological and non-pharmacological treatments should be used cautiously in patients with fibromyalgia, bearing in mind the patients' underlying disorders and the potential interactions of the therapies. PMID- 22094199 TI - Fatigue and fibromyalgia syndrome: clinical and neurophysiologic pattern. AB - The concept of 'fatigue' is strictly related to parameters of the setting in which fatigue is measured. Therefore, it is mandatory to provide a definition of fatigue and the modalities of its use. This is of pivotal importance with regard to the fibromyalgia (FM) syndrome, where fatigue is the most invalidating symptom and where, paradoxically, no clear and widely accepted definition of fatigue is available in the literature as yet. In the clinical setting, fatigue can be measured by different methods of various complexity. The simplest technique to assess fatigue involves the use of a visual analogue scale (VAS); however, a number of scales with differing levels of complexity are available for use. It is, often, difficult to detach the term 'fatigue' from tiredness and task failure, which correspond to two completely distinguished forms of fatigue: one with central origin (tiredness) and another which is localised within the muscle (peripheral muscle fatigue). The former is related to changes in motor-unit recruitment strategies, whereas the latter is attributed to changes in membrane properties. To extensively assess fatigue and, partially, to avoid confusion among the types of fatigue described above, a number of laboratory tests have been developed; among these, there are multichannel surface electromyography (EMG) recordings. Using this type of an approach, it is possible the estimation of motor unit location within the muscle, the decomposition of the surface EMG (sEMG) interference signal into constituent trains of motor unit action potentials (MUAPs) and the analysis of single unit properties. PMID- 22094200 TI - Clinimetric evaluations of patients with chronic widespread pain. AB - Assessing chronic widespread pain (CWP) and its impact on physical, emotional and social function requires multidimensional qualitative and health-related quality of life (HRQL) instruments. The recommendations of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) concerning outcome measurements for pain trials are useful for making routine assessments, the most significant of which include pain, fatigue, disturbed sleep, physical functioning, emotional functioning, patient global ratings of satisfaction and HRQL. However, despite the growing spread of instruments and theoretical publications devoted to measuring the various aspects of chronic pain, there is little widespread agreement, and no unified approach has yet been devised. There is therefore still considerable scope for the development of consensus around a core set of measures and response criteria, as well as for the development and refinement of the related instruments, standardised assessor training, the cross cultural adaptation of health status questionnaires, electronic data capture and the introduction of valid, reliable and responsive standardised quantitative measurements into routine clinical care. Clinicians need to be aware of the psychometric properties of the instruments used, including their levels of imprecision and minimum clinically important differences (those indicating a meaningful change in clinical status). This article reviews a selection of the instruments used to assess CWP patients, including validated newly developed and well-established screening instruments, and discusses their advantages and limitations. PMID- 22094201 TI - Neuroimaging of fibromyalgia. AB - The primary symptom of fibromyalgia is widespread pain. This symptom is accompanied by secondary symptoms, such as cognitive difficulties and sensitivity to painful stimulation, and by numerous co-morbidities. The first neuroimaging studies addressed the primary symptom by examining differences between patients and controls using single-photon-emission-computed tomography (SPECT). Subsequent studies focussed on the secondary symptom of increased sensitivity to painful stimulation. Functional MRI (fMRI) studies using the blood-oxygen-level-dependent (BOLD) method to assess brain activation demonstrated augmented sensitivity to painful pressure and the association of this augmentation with variables such as depression and catastrophising. These studies have also assessed brain processes associated with cognitive dysfunction. Neuroimaging studies of fibromyalgia have now come full circle, using new techniques to provide information about differences that may relate to underlying mechanisms and the primary symptom of widespread pain. Using a wide array of techniques, these studies have found differences in opioid receptor binding, concentration of metabolites associated with neural processing in pain-related regions and differences in functional brain networks and in regional brain volume and in white-matter tracks. This array of neuroimaging techniques continues to provide increasing information about supraspinal mechanisms associated with fibromyalgia that will aid in diagnosis, including identification of diagnostic subgroups, the development of new efficacious treatments that address both causes and symptoms and the matching of patients to treatments. PMID- 22094202 TI - Pharmacotherapy of fibromyalgia. AB - There have been substantial advances in the pharmacotherapy of fibromyalgia (FM), which have occurred in parallel with advances in our understanding of the pathophysiology of FM in the past several years. Consortia of researchers have established a core set of symptom domains, which constitute the condition of FM, including pain, fatigue, sleep and mood disturbance and cognitive dysfunction, which significantly impact a patient's overall well-being and ability to function. Outcome measures, which assess these domains, both singly and in composite format, are showing increasing reliability to discriminate between the treatment and placebo arms in clinical trials of emerging therapies, which are targeting the pathophysiologic mechanisms of FM. Several different medications, including the serotonin and norepinephrine reuptake inhibitors, duloxetine and milnacipran, and the alpha(2)delta modulator, pregabalin, have been approved by the Food and Drug Administration (FDA) for the management of FM, based on their clinically meaningful and durable effect on pain in monotherapy trials. They also have been shown to beneficially effect patient global impression of change, function and variably other key symptom domains, such as fatigue, sleep disturbance and cognition. Other medicines, although they have not gone through the formal approval process, have also shown efficacy in multiple domains of FM. Although combination trials have generally not yet been performed, the combined use of medicines with complementary mechanisms of action is rational, and, when done with appropriate caution, will likely be shown to be safe and well tolerated. Adjunctive therapy with medicines targeted at specific symptom domains, such as sleep, as well as treatments aimed at common co-morbid conditions, such as irritable bowel syndrome, or disease states, such as rheumatoid arthritis, should be considered for the purpose of reducing the patient's overall symptom burden. Current therapies neither completely treat FM symptoms nor benefit all patients; thus, further research on new therapies with different mechanisms and side-effect profiles is needed. PMID- 22094203 TI - Non-pharmacological treatment of chronic widespread musculoskeletal pain. AB - Individuals with chronic widespread pain, including those with fibromyalgia, pose a particular challenge to treatment, given the modest effectiveness of pharmacological agents for this condition. The growing consensus indicates that the best approach to treatment involves the combination of pharmacological and non-pharmacological interventions. Several non-pharmacological interventions, particularly exercise and cognitive-behavioural therapy (CBT), have garnered good evidence of effectiveness as stand-alone, adjunctive treatments for patients with chronic pain. In this article, evidenced-based, non-pharmacological management techniques for chronic widespread pain are described by using two broad categories, exercise and CBT. The evidence for decreasing pain, improving functioning and changing secondary symptoms is highlighted. Lastly, the methods by which exercise and CBT can be combined for a multi-component approach, which is consistent with the current evidence-based guidelines of several American and European medical societies, are addressed. PMID- 22094204 TI - Multidisciplinary approach to fibromyalgia: what is the teaching? AB - Fibromyalgia (FM) is a rheumatic disease that is characterised by chronic musculoskeletal pain, stiffness, fatigue, sleep and mood disorder. FM patients demonstrate dysregulation of pain neurotransmitter function and experience a neurohormone-mediated association with sleep irregularities. There are currently no instrumental tests or specific diagnostic markers for FM, and many of the existing indicators are only significant for research purposes. Anti-depressants, non-steroidal anti-inflammatory drugs (NSAIDS), opioids, sedatives, muscle relaxants and antiepileptics have all been used to treat FM with varying results. It has been shown that interdisciplinary treatment programmes lead to greater improvements in subjective pain and function than monotherapies. Physical exercise and multimodal cognitive behavioural therapy are the most widely accepted and beneficial forms of non-pharmacological therapy. PMID- 22094205 TI - Future perspectives in generalised musculoskeletal pain syndromes. AB - This article describes contemporary controversies regarding two categories of soft-tissue pain (STP)--chronic widespread pain and fibromyalgia syndrome. The tone is more editorial than review didactic. It draws upon history to explain current trends that project possible future implications. It begins with an orientation to classification of STP pain conditions and contrasts two ways to make the fibromyalgia diagnosis. Epidemiological data will be placed in perspective. The article ends with the voice of a non-physician patient advocate. STP classification divides relevant painful conditions into three subgroups, depending on the extent of body involvement (localised, regional and generalised). Fibromyalgia syndrome, in the generalised STP category, is distinguished from other types of chronic widespread pain by virtue of its greater severity. During the past 20 years, the diagnosis of fibromyalgia was based on a research classification (1990 American College of Rheumatology Research Classification Criteria (1990 ACR RCC)) that requires a history of chronic widespread pain and the examination finding of widespread mechanical allodynia. A new approach (2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria (2010 ACR FDC)), validated for clinical use, still requires a history of chronic widespread pain, but the examination is replaced by a historical assessment of co-morbid symptom severity. The populations identified by the two criteria are similar but not identical. Misuse of the new criteria could expand fibromyalgia from 2 to 10% of the general population. Avoidance of the term 'fibromyalgia' could return it to the obscurity from whence it came, leaving a much larger problem in its stead. PMID- 22094206 TI - A qualitative examination of body image threats using Social Self-Preservation Theory. AB - This study sought to identify and describe comfortable and uncomfortable body related situations of young women, as well as describe their responses to such situations and strategies they used to cope with body-related threats, using Social Self-Preservation Theory (SSPT) as a guiding framework. Interviews were conducted with college women (N=23). A theoretical thematic analysis approach was taken to identify, code, and report themes. In general, participants found it difficult to identify specific comfortable situations and responses in those situations. Comfortable situations were characterized by the presence of supportive others and feelings of general calmness and lowered body awareness or self-presentational concerns. Findings regarding uncomfortable body-related situations indicated that the context (e.g., presence of others, body exposure), responses (e.g., embarrassment, inadequacy, awareness of others' evaluations, faster heart rate), and coping strategies (e.g., avoidance, concealing behaviors) described by participants were consistent with SSPT. PMID- 22094207 TI - Dopamine control of LH release in the tench (Tinca tinca). AB - Tench (Tinca tinca) is apparently the only known member of the Cyprinidae in which ovulation is stimulated following administration of a low dose of GnRH analogue (GnRHa) without a dopamine inhibitor. This study evaluated LH release effectiveness of the most commonly used GnRHa and clarified whether LH secretion followed by ovulation is subject to inhibitory dopaminergic control in tench. Fish were intraperitoneally injected with three types of GnRHa, GnRHa with dopamine inhibitor metoclopramide (combined treatment), or the dopamine inhibitor metoclopramide alone. LH concentrations at five sampling times (0, 6, 12, 24, and 33 h) together with ovulation success and fecundity index were recorded. The combined treatment triggered an almost immediate LH release peak with a gradual decline, and resulted in a high ovulation rate. In contrast to the combined treatment, an application of GnRHa alone at 10 MUg kg(-1) induced gradual increase of LH concentrations with peaks close to ovulation time, and with high ovulation success. Significant differences in LH concentrations at 6 and 12h and no differences in ovulation success were found between the combined and the GnRHa alone treatments. Metoclopramide alone induced a small increase in LH with no ovulation. The study presents clear evidence of dopaminergic control of LH release in tench, with a high ovulation rate obtained after application of GnRHa alone or in combination with dopamine inhibitor. PMID- 22094208 TI - The role of growth hormone in growth, lipid homeostasis, energy utilization and partitioning in rainbow trout: interactions with leptin, ghrelin and insulin-like growth factor I. AB - The growth-promoting effects of in vivo growth hormone (GH) treatment were studied in relation to size and lipid content of energy stores including liver, mesentery, white muscle and belly flap in rainbow trout. In order to elucidate endocrine interactions and links to regulation of growth, adiposity and energy metabolism, plasma levels of GH, insulin-like growth factor I (IGF-I), leptin (Lep) and ghrelin, were assessed and correlated to growth and energy status. In addition tissue-specific expression of lepa1 mRNA was examined. Juvenile rainbow trout were implanted with sustained-release bovine GH implants and terminally sub sampled at 1, 3 and 6 weeks. GH increased specific growth rate, reduced condition factor (CF) and increased feed conversion efficiency resulting in a redistribution of energy stores. Thus, GH decreased mesenteric (MSI) and liver somatic index (LSI). Lipid content of the belly flap increased following GH treatment while liver and muscle lipid content decreased. Independent of GH substantial growth was accompanied by an increase in muscle lipids and a decrease in belly flap lipids. The data suggest that the belly flap may function as an energy buffering tissue during episodes of feeding and lean growth. Liver and muscle lipids were positively correlated to body weight, indicating a size dependent change in adiposity. Hepatic lepa1 mRNA positively correlated to MSI and CF and its expression decreased following GH treatment, coinciding with decreased hepatic lipid content. Plasma Lep was positively correlated to MSI and belly flap lipid content, suggesting that Lep may communicate energy status. In summary, the observed GH tissue-specific effects on lipid metabolism in rainbow trout highlight the complex physiology of the energy reserves and their endocrine control. PMID- 22094209 TI - Is the new ICRP eye dose limit justified? PMID- 22094210 TI - Hpn protein as a mediator between Helicobacter pylori infection and Alzheimer's disease in sub-populations worldwide. PMID- 22094212 TI - [A drink can harm the baby in the womb]. PMID- 22094211 TI - Potential role of TNF alpha blockers in delaying the progression of hepato-renal syndrome. AB - Hepatorenal syndrome occurs in patients with advanced liver cirrhosis and is associated with functional renal impairment and poor prognosis. These patients present a challenge to physicians and management strategies. Although various pharmacological therapies are available, large randomized controlled trials are required to determine which treatment modality is most effective to improve survival rates along with its dose and duration of treatment. The overproduction of tumor necrosis factor-alpha (TNF-alpha) has been postulated to play a role in progression of this disease, being associated with hyperdynamic circulation and inflammatory process. Moreover, increasing the levels of TNF-alpha during the course of hospitalization is suggested to be associated with increased mortality. Hence the role of TNF-alpha inhibitors, such as pentoxifylline, may prove to be become a new clinical pathway. Various randomized clinical trials have demonstrated a significant reduction in mortality in patients receiving pentoxifylline, in comparison to the control group. This survival rate benefit was associated with decrease in the incidence of hepatorenal syndrome in these patients. We propose a double-blinded trial to test the hypothesis, in which patients with advanced liver disease without evidence of hepatorenal syndrome are recruited. The control group receives the standard management while the case group receives standard management along with TNF-alpha blockers. If the cases develop hepatorenal syndrome at a significant duration later in comparison to the control group, our hypothesis will be confirmed. Our methodology is limited due to costs of TNF-alpha inhibitors in a developing country setup, hence it has only been proposed as a hypothesis. If the recommended trial confirms our hypothesis, we might see favorable outcomes and improved survival rates in patients with decompensated liver diseases. PMID- 22094213 TI - [Reduced synthesis of coenzyme Q10 may cause statin related myopathy]. AB - Statin treatment can cause muscular side effects. It has been suggested that the mechanism is reduced synthesis of coenzyme Q10 (coQ10) and a subsequent dysfunction of the respiratory chain. A literature review resulted in insufficient evidence supporting this theory. It is uncertain whether intramuscular levels of coQ10 and mitochondrial function are affected by statin therapy and whether the symptoms of myopathy can be alleviated with coQ10 supplementation. Nevertheless, due to a favourable safety profile, coQ10 can be tested in patients whose muscular symptoms cannot be managed otherwise. PMID- 22094214 TI - [Audience response-systems enhance the learning environment]. AB - The purpose of this article was to describe the possibilities gained by using an electronic voting system (EVS), the existing evidence to determine whether an EVS affects learning proceeds, challenges in EVS and perspectives for EVS in Danish medical training. Audience Response-Systems (ARS) seem suited to enhance participants' activity and attention. The technology as such holds the potential to enhance learning outcome, but changes in the pedagogical method are needed. More studies examining the use of new wireless, mobile voting systems are required. PMID- 22094215 TI - [Lichen sclerosus--a neglected disease]. AB - We present a small review of lichen sclerosus in women and an update on the newest knowledge, e.g. on calcineurin inhibitors as a choice of treatment. The goal is to put more focus on the disease in Denmark because it is so often diagnosed only with a great delay. We further emphasize the importance of follow up on these patients, due to the risk of cancer, the great influence of the disease on quality of life and the risk of structural changes in the vulva region. PMID- 22094216 TI - [Primary autoimmune neutropenia in children]. AB - Primary autoimmune neutropenia (AIN) is characterised by severe neutropenia and the presence of granulocyte reactive autoantibodies. The pathogenesis of the disease remains unknown and the disease is believed to be underdiagnosed. AIN occurs predominantly at the age of 6-24 months and despite severe neutropenia the symptomatology covers mainly benign infections. Serious bacterial infections might occur and some patients thus may benefit from treatment with prophylactic antibiotics or granulocyte growth factor. Spontaneous remission usually occurs within 30 months from the time of diagnosis. PMID- 22094217 TI - [Autoimmune neutropenia in children]. AB - Case reports of three children with autoimmune neutropenia are presented. The children had a number of infections, which required antibiotic treatment, mostly respiratory tract infections, but one child had a septic coxitis. During a follow up period of 1-3 years, only one patient showed complete remission after 15 months of neutropenia. One child was treated with granulocyte colony-stimulating factor without effect, whereas two children received prophylactic antibiotics with clinical benefit. In view of the frequent infections and benefit of prophylactic measures, children with neutropenia or an inappropriately low neutrophil count during bacterial infections should be evaluated for autoimmune neutropenia. PMID- 22094218 TI - [Early stage of Acanthamoeba keratitis]. AB - We present a case of early detected Acanthamoeba keratitis. The patient was a 31 year-old female with keratitis who was referred to our clinic. Upon arrival the patient presented with subepithelial corneal infiltrates and radiating neuritis. In vivo confocal microscopy showed Acanthamoeba cysts and treatment was initiated. Polymerase chain reaction analysis later confirmed the diagnosis and after three months symptoms had abated and vision was 1.0 (6/6). We confirm that an early diagnosis af Acanthamoeba keratitis is pivotal. PMID- 22094219 TI - [Treatment of acute myeloid leukaemia without blood transfusion in a member of Jehovah's Witnesses]. AB - We present a case in which a young woman was diagnosed with acute myeloid leukaemia, FAB-classification type M2. As a member of Jehovah's Witnesses she refused to accept any treatment involving blood transfusions. A modified induction and consolidation chemotherapy regimen was applied, tailored to reduce prolonged myelosuppression. Despite severe anaemia, she survived to achieve complete remission. She is currently under treatment-free observation after two courses of consolidation treatment. PMID- 22094220 TI - [Traumatic duodenal perforation in a 16 month-old girl]. AB - Duodenal injury following a blunt abdominal trauma is a rare condition. It poses a diagnostic challenge since symptoms are often subtle in the beginning and the trauma may initially remain undisclosed. We present a case of a 16 month-old girl, who was admitted to hospital due to critical illness after a tumble the day before. An explorative laparotomy revealed a perforation of the duodenum. This case demonstrates the importance of thoroughly evaluating anamnesis information and emphasises the need of considering a variety of potential diagnoses when assessing the critically ill child. PMID- 22094221 TI - [Picture of the month: Verotoxin-producing Escherichia coli]. PMID- 22094222 TI - Hyperpolarization-activated cation current contributes to spontaneous network activity in developing neocortical cultures. AB - The mechanisms underlying spontaneous burst activity (SBA), appearing in networks of embryonic cortical neurons at the end of the first week in vitro, remain elusive. Here we investigated the contribution of the hyperpolarization-activated cation current (I(h)) to SBA in cortical cultures of GAD67-GFP mice. I(h) current could be detected in GFP-positive large GABAergic interneurons (L-INs) and glutamatergic principal neurons (PNs) as early as DIV 5. Under current-clamp conditions, blockers of I(h) current, ZD7288 and Cs+, abolished the voltage sag and rebound depolarization. ZD7288 induced a hyperpolarization concomitant with an increase in the membrane input resistance in L-INs and PNs. Voltage-clamp recordings revealed I(h) as slowly activating inward current with a reversal potential close to -50 mV and a mid-activation point around -90 mV. Both, ZD7288 (1-10 MUM) and Cs+ (1-2 mM) reduced SBA, spontaneous activity-driven Ca2+ transients, and frequency as well as amplitude of miniature GABAergic postsynaptic currents. Immunocytochemistry and Western blot demonstrated that HCN1 and HCN2 were the prevalent isoforms of HCN channels expressed in L-INs and PNs. These results suggest an important contribution of HCN channels to the maintenance of SBA in embryonic cortical cultures. PMID- 22094223 TI - Superoxide dismutase 1 encoding mutations linked to ALS adopts a spectrum of misfolded states. AB - BACKGROUND: Mutations in superoxide dismutase 1 (SOD1), which are one cause of familial amyotrophic lateral sclerosis (fALS), induce misfolding and aggregation of the protein. Misfolding can be detected by the binding of antibodies raised against peptide epitopes that are normally buried in the native conformation, shifts in solubility in non-ionic detergents, and the formation of macromolecular inclusions. In the present study, we investigate the relationship between detergent-insoluble and sedimentable forms of mutant SOD1, forms of mutant SOD1 with aberrantly accessible epitopes, and mutant protein in inclusions with the goal of defining the spectrum of misfolded states that mutant SOD1 can adopt. RESULTS: Using combined approaches in cultured cell models, we demonstrate that a substantial fraction of mutant SOD1 adopts a non-native conformation that remains soluble and freely mobile. We also show that mutant SOD1 can produce multimeric assemblies of which some are insoluble in detergent and large enough to sediment by ultracentrifugation and some are large enough to detect visually. Three conformationally restricted antibodies were found to be useful in discriminating mal-folded forms of mutant SOD1. An antibody termed C4F6 displays properties consistent with recognition of soluble, freely mobile, mal-folded mutant SOD1. An antibody termed SEDI, which recognizes C-terminal residues, detects larger inclusion structures as well as soluble misfolded entities. An antibody termed hSOD1, which recognizes aa 24-36, detects an epitope shared by soluble non natively folded WT and mutant SOD1. This epitope becomes inaccessible in aggregates of mutant SOD1. CONCLUSIONS: Our studies demonstrate how different methods of detecting misfolding and aggregation of mutant SOD1 reveal different forms of aberrantly folded protein. Immunological and biochemical methods can be used in combination to detect soluble and insoluble misfolded forms of mutant SOD1. Our findings support the view that mutant SOD1 can adopt multiple misfolded conformations with the potential that different structural variants mediate different aspects of fALS. PMID- 22094224 TI - Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy. AB - The alkylating agent temozolomide (TMZ) is the major chemotherapeutic drug used clinically in the treatment of malignant gliomas. This study investigated the mechanism behind TMZ-induced cell death and the possibility that resveratrol might increase TMZ efficacy. TMZ induced both apoptotic cell death and cytoprotective autophagy through a reactive oxygen species (ROS) burst and extracellular signal-regulated kinase (ERK) activation, which was suppressed by resveratrol, resulting in a decrease in autophagy and an increase in apoptosis, suggesting that the ROS/ERK pathway plays a crucial role in the fate of cells after TMZ treatment. Isobolographic analysis indicated that the combination of TMZ and resveratrol has a synergistic effect. Moreover, an in vivo mouse xenograft study also showed that coadministration of resveratrol and TMZ reduced tumor volumes by suppressing ROS/ERK-mediated autophagy and subsequently inducing apoptosis. Taken together, our data indicate that TMZ-induced ROS/ERK-mediated autophagy protected glioma cells from apoptosis, and the combination of resveratrol with TMZ could improve the efficacy of chemotherapy for brain tumors. PMID- 22094226 TI - A quantitative method for evaluating inferior glenohumeral joint stiffness using ultrasonography. AB - Subluxation of the affected shoulder in post-stroke patients is associated with nerve disorders and muscle fatigue. Clinicians must be able to accurately and reliably measure inferior glenohumeral subluxation in patients to provide appropriate treatment. However, quantitative methods for evaluating the laxity and stiffness of the glenohumeral joint (GHJ) are still being developed. The aim of this study was to develop a new protocol for evaluating the laxity and stiffness of the inferior GHJ using ultrasonography under optimal testing conditions and to investigate changes in the GHJ from a commercially available humerus brace and shoulder brace. Multistage inferior displacement forces were applied to create a glide between the most cephalad point on the visible anterosuperior surface of the humeral head and coracoid process in seven healthy volunteers. GHJ stiffness was defined as the slope of the linear regression line between the glides and different testing loads. The testing conditions were defined by different test loading mechanisms (n=2), shoulder constraining conditions (n=2), and loading modes (n=4). The optimal testing condition was defined as the condition with the least residual variance of measured laxity to the calculated stiffness under different testing loads. A paired t-test was used to compare the laxity and stiffness of the inferior GHJ using different braces. No significant difference was identified between the two test loading mechanisms (t=0.218, p=0.831) and two shoulder constraining conditions (t=-0.235, p=0.818). We concluded that ultrasonographic laxity measurements performed using a pulley set loading mechanism was as reliable as direct loading. Additionally, constraining the unloaded shoulder was proposed due to the lower mean residual variance value. Moreover, pulling the elbow downward with loading on the upper arm was suggested, as pulling the elbow downward with the elbow flexed and loading on the forearm may overestimate stiffness and pain in the inferior GHJ at the loading point due to friction between the wide belt and skin. Furthermore, subjects wearing a humerus brace with a belt, which creates the effect of lifting the humerus toward the acromion, had greater GHJ stiffness compared to subjects wearing a shoulder brace without a belt to lift the humerus under the proposed testing conditions. This study provides experimental evidence that shoulder braces may reduce GHJ laxity under an external load, implying that the use of a humeral brace can prevent subluxation in post-stroke patients. The resulting optimal testing conditions for measuring the laxity and stiffness of the GHJ is to constrain the unloaded shoulder and bend the loaded arm at the elbow with loading on the upper arm using a pulley system. PMID- 22094227 TI - Telling the story of XX sex reversal in the goat: highlighting the sex-crossroad in domestic mammals. AB - The conditions for sex reversal in vertebrate species have been studied extensively and have highlighted numerous key factors involved in sex differentiation. We review here the history of the development of knowledge, referring to one example of complete female-to-male XX sex reversal associated with a polled phenotype in the goat. The results and hypotheses concerning this polled intersex syndrome (PIS) are then presented, firstly with respect to the transcriptional regulatory effects of the PIS mutation, and secondly regarding the role of the main ovarian-differentiating factor in this PIS locus, the FOXL2 gene. PMID- 22094225 TI - Rotenone activates phagocyte NADPH oxidase by binding to its membrane subunit gp91phox. AB - Rotenone, a widely used pesticide, reproduces parkinsonism in rodents and associates with increased risk for Parkinson disease. We previously reported that rotenone increased superoxide production by stimulating the microglial phagocyte NADPH oxidase (PHOX). This study identified a novel mechanism by which rotenone activates PHOX. Ligand-binding assay revealed that rotenone directly bound to membrane gp91(phox), the catalytic subunit of PHOX; such binding was inhibited by diphenyleneiodonium, a PHOX inhibitor with a binding site on gp91(phox). Functional studies showed that both membrane and cytosolic subunits were required for rotenone-induced superoxide production in cell-free systems, intact phagocytes, and COS7 cells transfected with membrane subunits (gp91(phox)/p22(phox)) and cytosolic subunits (p67(phox) and p47(phox)). Rotenone elicited extracellular superoxide release in p47(phox)-deficient macrophages suggested that rotenone enabled activation of PHOX through a p47(phox) independent mechanism. Increased membrane translocation of p67(phox), elevated binding of p67(phox) to rotenone-treated membrane fractions, and coimmunoprecipitation of p67(phox) and gp91(phox) in rotenone-treated wild-type and p47(phox)-deficient macrophages indicated that p67(phox) played a critical role in rotenone-induced PHOX activation via its direct interaction with gp91(phox). Rac1, a Rho-like small GTPase, enhanced p67(phox)-gp91(phox) interaction; Rac1 inhibition decreased rotenone-elicited superoxide release. In conclusion, rotenone directly interacted with gp91(phox); such an interaction triggered membrane translocation of p67(phox), leading to PHOX activation and superoxide production. PMID- 22094228 TI - Interventions for coordination of walking following stroke: systematic review. AB - Impairments in gait coordination may be a factor in falls and mobility limitations after stroke. Therefore, rehabilitation targeting gait coordination may be an effective way to improve walking post-stroke. This review sought to examine current treatments that target impairments of gait coordination, the theoretical basis on which they are derived and the effects of such interventions. Few high quality RCTs with a low risk of bias specifically targeting and measuring restoration of coordinated gait were found. Consequently, we took a pragmatic approach to describing and quantifying the available evidence and included non-randomised study designs and limited the influence of heterogeneity in experimental design and control comparators by restricting meta analyses to pre- and post-test comparisons of experimental interventions only. Results show that physiotherapy interventions significantly improved gait function and coordination. Interventions involving repetitive task-specific practice and/or auditory cueing appeared to be the most promising approaches to restore gait coordination. The fact that overall improvements in gait coordination coincided with increased walking speed lends support to the hypothesis that targeting gait coordination gait may be a way of improving overall walking ability post-stroke. However, establishing the mechanism for improved locomotor control requires a better understanding of the nature of both neuroplasticity and coordination deficits in functional tasks after stroke. Future research requires the measurement of impairment, activity and cortical activation in an effort to establish the mechanism by which functional gains are achieved. PMID- 22094229 TI - Influence of BDNF variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia. AB - AIM: The present study aimed to explore whether some single nucleotide polymorphisms (SNPs) within the BDNF gene could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia, and whether they could predict clinical outcomes in Korean inpatients treated with antidepressants, mood stabilizers and antipsychotics, respectively. METHODS: One hundred and forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 5 BDNF SNPs (rs2030324, rs7103873, rs10835210, rs11030101 and rs6265). Baseline and final clinical measures--including the Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Positive and Negative Symptoms Scale for patients with MD, BD and schizophrenia, respectively--were recorded. RESULTS: rs10835210 CA and rs11030101 AT genotype frequencies were higher in BD and schizophrenia patients than in healthy and MD subjects. No significant association was found with clinical improvement. DISCUSSION: Our findings provide evidence of an association between BDNF and BD and schizophrenia. However, taking into account the several limitations of our study, including the moderately small sample size, further research is needed to draw more definitive conclusions. PMID- 22094230 TI - The effects of huwentoxin-I on the voltage-gated sodium channels of rat hippocampal and cockroach dorsal unpaired median neurons. AB - Huwentoxin-I (HWTX-I) is a 33-residue peptide isolated from the venom of Ornithoctonus huwena and could inhibit TTX-sensitive voltage-gated sodium channels and N-type calcium channels in mammalian dorsal root ganglion (DRG) neurons. However, the effects of HWTX-I on mammalian central neuronal and insect sodium channel subtypes remain unknown. In this study, we found that HWTX-I potently inhibited sodium channels in rat hippocampal and cockroach dorsal unpaired median (DUM) neurons with the IC(50) values of 66.1+/-5.2 and 4.80+/ 0.58nM, respectively. Taken together with our previous work on DRG neurons (IC(50)~55nM), the order of sodium channel sensitivity to HWTX-I inhibition was insect central DUM?mammalian peripheral>mammalian central neurons. HWTX-I exhibited no effect on the steady-state activation and inactivation of sodium channels in rat hippocampal and cockroach DUM neurons. PMID- 22094231 TI - Expression patterns of the immunosuppressive proteins PD-1/CD279 and PD-L1/CD274 at different stages of cutaneous T-cell lymphoma/mycosis fungoides. PMID- 22094232 TI - Levamisole-induced vasculopathy: a report of 2 cases and a novel histopathologic finding. AB - Although cocaine-induced pseudovasculitis and urticarial vasculitis have been reported in the past, levamisole-induced vasculopathy with ecchymosis and necrosis, termed here LIVEN, has only recently been described in association with cocaine use. Levamisole, a veterinary antihelminthic agent used previously as an immunomodulating agent, is present as a "cutting agent" in approximately two thirds of the cocaine currently entering the United States. Levamisole is believed to potentiate the effects of cocaine and may also be used as a "signature" for tracing its market distribution. Herein, we report 2 cases of LIVEN in patients with histories of chronic cocaine use. In both the cases, a temporal association with neutropenia preceding the eruption was noted. A novel histopathologic finding present only in the second case was the presence of extensive interstitial and perivascular neovascularization. Our 2 cases reaffirm that neutropenia may precede the cutaneous eruption of LIVEN. Case 2 extends the spectrum of histopathologic findings to include the novel phenomenon of neovascularization-hitherto unreported in this entity. PMID- 22094233 TI - Lack of correlation between immunohistochemical expression of CKIT and KIT mutations in atypical acral nevi. AB - BACKGROUND: Given the correlation between KIT mutations and immunohistochemical expression of CKIT in acral melanoma, our aim was to confirm the utility of CKIT detection as a screening tool for KIT genotyping in atypical acral nevi and to ascertain the frequency of KIT mutations in the same. DESIGN: Immunohistochemical staining for CKIT was performed and staining criteria were the following: negative = <10%, 1 = 11%-49%, and 2 = >50% of cells. Intensity grading was as follows: negative = 0, weak = 1, moderate = 2, and strong = 3. Genomic amplification was performed on KIT exons commonly mutated in acral melanomas (11, 13, and 17) from atypical acral nevi (23) ranging in severity from mild (9), moderate (10), and severe (4). The control group included acral nevi without atypia (19). For purposes of statistical analyses, cases with 11% or more staining of cells were compared with negative cases and cases with a staining intensity of 1 or higher were compared with the negatives. RESULTS: Immunohistochemical analyses revealed the following: positive staining with an intensity 1 or more in 18 of 22 (82%) of cases with atypia (5 mild; 9 moderate and 4 severe) and in 13 of 17 (76%) nevi without atypia with no statistically significant differences between both groups. Genomic analyses of exon regions revealed no abnormalities in "hotspots" frequently associated with point mutations in acral melanomas. CONCLUSIONS: Our findings indicate a lack of correlation between immunohistochemical expression of CKIT and KIT mutations in atypical acral nevi. Atypical acral nevi do not exhibit genetic alterations in KIT associated with acral melanomas. PMID- 22094234 TI - Immunogenicity and reactogenicity of a monovalent inactivated 2009 influenza A vaccine in adolescents: with special reference to pre-existing antibody. AB - OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a monovalent 2009 pandemic influenza vaccine in Japanese adolescents. STUDY DESIGN: A total of 111 junior high school and high school students aged 13 to 18 years participated. Subjects received two doses of a monovalent inactivated unadjuvanted 2009 influenza A vaccine. Immunogenicity of the vaccine was evaluated according to the international criteria. We also asked subjects to report adverse reactions. RESULTS: After the first dose of vaccine, the seroprotection rate was 91% (95% CI, 85%-96%), the seroconversion rate was 78% (70%-86%), and the geometric mean titer ratio was 11.9 in all subjects. Antibody titers achieved did not differ significantly after the first and the second doses. With multivariate analysis, an independent negative effect of a prevaccination titer of >=1:40 on >=4 fold antibody increase was indicated. No serious adverse reaction was reported. CONCLUSION: The monovalent pandemic vaccine generally was safe, and a single dose of the vaccine given to adolescents induced sufficient immunity. Pre-existing antibody showed substantial effect on antibody response. The effect of pre existing titer should be considered when evaluating the immunogenicity of influenza vaccines, especially in studies conducted during pandemic waves. PMID- 22094235 TI - The modern staged repair of classic bladder exstrophy: a detailed postoperative management strategy for primary bladder closure. AB - PURPOSE: Successful primary bladder closure of classic bladder exstrophy sets the stage for development of adequate bladder capacity and eventual voided continence. The postoperative pathway following primary bladder closure at the authors' institution is quantitatively and qualitatively detailed. MATERIALS AND METHODS: Sixty-five consecutive newborns (47 male) undergoing primary closure of classic bladder exstrophy were identified and data were extracted relating to immediate postoperative care. Overall success rate was utilized to validate the pathway. RESULTS: Mean age at time of primary closure was 4.6 days and mean hospital stay was 35.8 days. Osteotomy was performed in 19 patients (mean age 8.8 days), and was not required in 39 infants (mean age 2.9 days). All patients were immobilized for 4 weeks. Tunneled epidural analgesia was employed in 61/65 patients. All patients had ureteral catheters and a suprapubic tube, along with a comprehensive antibiotic regimen. Postoperative total parenteral nutrition was commonly administered, and enteral feedings started around day 4.6. Our success rate of primary closure was 95.4%. CONCLUSIONS: A detailed and regimented plan for bladder drainage, immobilization, pain control, nutrition, antimicrobial prophylaxis, and adequate healing time is a cornerstone for the postoperative management of the primary closure of bladder exstrophy. PMID- 22094236 TI - Multidetector computed tomography detection of a very unusual double coronary fistula from left anterior descending coronary artery to pulmonary artery and descending aorta. PMID- 22094237 TI - The role of echocardiography in quantification of left ventricular dyssynchrony: state of the art and future directions. AB - This article discusses how echocardiography can be applied to quantify dyssynchrony in patients who are evaluated for cardiac resynchronization therapy (CRT). A number of echocardiographic indices have been proposed as markers of success of CRT. However, when tested against QRS width in prospective clinical trials, none of the echocardiographic indices are proven to give clinical benefit. One important message in this review is that future studies should focus on approaches which can differentiate between electrical and non-electrical aetiologies of dyssynchrony, since only electrical dyssynchrony is likely to respond to CRT. Just measuring velocity indices does not identify the aetiology. Myocardial strain appears more promising, but one should be aware that timing of peak systolic strain is determined not only by electrical conduction. It is proposed to use onset septal shortening during pre-ejection for timing of earliest left ventricular (LV) electrical activation. One should take into account potential ischaemia, scarring, and other structural changes as contributors to dyssynchrony. As a method to identify electrical dyssynchrony, the authors propose to use time of active force generation as defined by LV pressure-strain loops. A non-invasive method to measure segmental pressure-strain loops is also proposed as a means to quantify the impact of dyssynchrony on distribution of myocardial work. Furthermore, it is important to be aware that LV dyssynchrony may have a combination of aetiologies, not all amenable for CRT. PMID- 22094238 TI - Non-invasive imaging in acute chest pain syndromes. AB - This review has the purpose of informing the reader about the current use of imaging techniques in patients presenting with acute chest pain to the emergency department. We will focus on three aspects of managing the patient with acute chest pain: Imaging to increase the number of correct diagnoses in the acute situation; Imaging to rule out other than coronary causes of chest pain; Use of imaging for risk stratification once myocardial infarction has been ruled out in the CPU. Special emphasis is given to how these management aspects are discussed in current guidelines on the management of patients with acute chest pain or acute coronary syndrome. PMID- 22094239 TI - Cardiac hybrid imaging. AB - Cardiac hybrid imaging combines different imaging modalities in a way where both modalities equally contribute to image information. The most common and best studied approach is to combine computed tomography coronary angiography (CTCA) and myocardial perfusion imaging either with single-photon emission computed tomography or with positron emission tomography (PET). This combination is a promising tool for evaluation of coronary artery disease since it allows visualization of coronary atherosclerotic lesions and their haemodynamic consequences in a single study and it appears to offer superior diagnostic accuracy when compared with stand-alone imaging. More recent applications are a combination of CTCA and cardiac magnetic resonance imaging by using software image fusion and utilization of commercially available hybrid PET/MRI scanners for cardiac applications. Currently, these methods have been reported only as case reports, but several potential applications also in cardiology can be anticipated. The development of new molecular imaging probes will also open completely new possibilities for guidance and monitoring of advanced therapies. This review will focus on the concepts and currently available clinical experiences from cardiac hybrid imaging as well as discuss the potential future applications. PMID- 22094240 TI - Relationships between intramuscular fat content, selected carcass traits, and fatty acid profile in bulls using a F2-population. AB - The quality and nutritional value of beef is related to the amount of intramuscular fat (IMF) as well as to its fatty acid composition. In this study the relations between the IMF content and the total fatty acid composition, the fatty acids (FA) of triacylglycerols (TG) and the FA of phospholipids (PL) in longissimus muscle of F(2) Charolais*German Holstein crossbred bulls have been analysed. Polyunsaturated fatty acids (PUFA, C18:2n-6; C18:3n-3) and stearic acid (C18:0) are strongly positively correlated to IMF in longissimus muscle at the quantitative level (mg/100g fresh tissue), but there are negative correlation coefficients for the relative proportion of these fatty acids to IMF. The relationships between IMF and the fatty acid profile of the subfractions TG and PL are lower compared to total muscle fat. Selected carcass fat traits are positively correlated to most of the fatty acids. PMID- 22094241 TI - Isolation and characterization of T cells from semen. AB - BACKGROUND: The male genital tract is of major importance in the transmission and acquisition of HIV-1. Studying cellular immunity in the male genital tract is important in development of HIV-1 vaccines protective at mucosal sites. Semen is the primary HIV-1 containing fluid released from the male genital tract and reducing virus levels in semen would also reduce HIV-1 spread. Characterizing lymphocytes from semen requires the isolation of viable T cells that can be analyzed by downstream applications such as flow cytometry. The aims of this study were to investigate the influence of various parameters on CD3(+) T cell yields from semen and to compare isolation methods to maximize CD3(+) T cell yields for the purpose of functional characterization by flow cytometry. METHODS: The influence of abstinence, storage temperature and time till processing on semen CD3(+) T cell yields was investigated. Seminal CD3(+) T cell yields were evaluated by comparing gradient separation, enzymatic digestion, filtration and magnetic bead capture. The function and viability of seminal CD4(+) and CD8(+) T cells were assayed by flow cytometry. RESULTS: We found that the use of pronase and cell strainers resulted in significantly higher CD3(+) T cell yields when compared to gradient separation alone. Positive selection of CD3(+) cells using magnetic bead purification resulted in significantly higher yields and improved resolution of lymphocyte subsets by flow cytometry. Processing of samples should occur as expediently as possible to maximize CD3(+) T cell yields. However, if this is not possible, loss of CD3(+) T cells can be minimized by storing samples at 37 degrees C for up to one day post ejaculation. CONCLUSIONS: We describe a simple method for the isolation of functional T cells from semen. Developing standardized methods for processing samples and measuring immunity in the male genital tract may be important in clinical trials of not only candidate HIV-1 vaccines, but in better understanding cellular immunity to a range of sexually transmitted infections of global significance. PMID- 22094242 TI - Diverse roles of the scaffolding protein RanBPM. AB - Ran-binding protein microtubule-organizing center (RanBPM) appears to function as a scaffolding protein in several signal transduction pathways. RanBPM is a crucial component of multiprotein complexes that regulate the cellular function by modulating and/or assembling with a wide range of proteins in different intracellular regions and thereby mediate diverse cellular functions. This suggests a role for RanBPM as a scaffolding protein. In this article, we have summarized the diverse functions of RanBPM and its interacting partners that have been investigated to date. Also, we have categorized the role of RanBPM into four divisions: RanBPM as a modulator/protein stabilizer, regulator of transcription activity, cell cycle and neurological functions. PMID- 22094243 TI - MRI as a tool for evaluation of oral controlled release dosage forms. AB - The magnetic resonance imaging (MRI) studies of controlled-release (CR) dosage forms can be roughly divided into two groups. The first comprises studies performed in static conditions (small solvent volumes and ambient temperature). Such studies have provided insight into molecular phenomena in hydrating polymeric matrices. The second group covers research performed in dynamic conditions (medium flow or stirring) related to drug dissolution. An important issue is supplementation of the MRI results with data obtained by complementary techniques, such as X-ray microtomography (MUCT). As we discuss here, an understanding of the mechanism underlying the release of the drug from the dosage form will lead to the development of detailed, molecularly defined, CR dosage forms. PMID- 22094244 TI - Determinants for successful marketing authorisation of orphan medicinal products in the EU. AB - In 2010, the European Regulation for Orphan Medicinal Products (OMPs) was in force for ten years. In this study we assessed possible determinants of applications for OMPs in the EU since 2000 that are associated with a successful marketing authorisation. Our analysis shows that clinical trial characteristics such as demonstrating convincing evidence of a beneficial effect on the primary endpoint, the selection of a clinically relevant endpoint, providing RCT data as pivotal study evidence and the submission of sound dose finding data are critical success factors. In addition, high medical need seems to counterweigh uncertainties about the scientific evidence in the benefit-risk assessment of OMPs. PMID- 22094246 TI - Is there a clinical future for polymeric nanoparticles as brain-targeting drug delivery agents? AB - Injectable nanosized carriers (5-250 nm) are actively studied as anticancer drug delivery agents for targeted drug delivery to the brain. Among these, polymeric nanoparticles (Np) have been studied since 1995, but only five of them recently started Phase I clinical trials, and none of these targets brain pathologies. To date, clinical trials for brain drug delivery have started for macromolecular- and nanocarrier-based systems in the treatment of brain tumors. This review, on the basis of the results obtained so far from preclinical studies, will critically consider the possibilities that polymeric Np have to reach the clinic as drug delivery agents for the brain, in comparison with other platforms. PMID- 22094247 TI - Collaboration between PcG proteins and MLL fusions in Leukemogenesis: an emerging paradigm. AB - PcG and TrxG proteins mostly with opposite transcriptional activities play key roles in normal and malignant development. In this issue of Cancer Cell, Tan et al. report an unexpected collaboration between CBX8 and MLL-AF9 in leukemia, revealing a far more complicated functional crosstalk between these master epigenetic regulators in oncogenesis. PMID- 22094245 TI - Biomimetic tissues on a chip for drug discovery. AB - Developing biologically relevant models of human tissues and organs is an important enabling step for disease modeling and drug discovery. Recent advances in tissue engineering, biomaterials and microfluidics have led to the development of microscale functional units of such models also referred to as 'organs on a chip'. In this review, we provide an overview of key enabling technologies and highlight the wealth of recent work regarding on-chip tissue models. In addition, we discuss the current challenges and future directions of organ-on-chip development. PMID- 22094248 TI - Platelets alter tumor cell attributes to propel metastasis: programming in transit. AB - Metastasis of epithelial tumors critically depends on acquisition of a disseminating phenotype that allows tumor cells to colonize distant organs. In this issue of Cancer Cell, Labelle et al. demonstrate that an epithelial mesenchymal-like transition can be induced by interaction between platelets and tumor cells. PMID- 22094249 TI - Power cut: inhibiting mitochondrial translation to target leukemia. AB - In this issue of Cancer Cell, Skrtic et al. demonstrate that inhibition of mitochondrial ribosomes with tigecycline, a known antimicrobial, selectively kills leukemia cells. This finding highlights the metabolic susceptibility of leukemia cells to mitochondrial translational inhibition and identifies a compound with significant efficacy in an in vivo preclinical model. PMID- 22094250 TI - The Two Faces of NF-kappaB Signaling in Cancer Development and Therapy. AB - Constitutive activation of NF-kappaB signaling can promote oncogenesis, providing a rationale for anticancer strategies that inhibit NF-kappaB signaling. Two recent publications in Genes & Development provide evidence that, in contexts where prosurvival signals derive from other oncogenes, NF-kappaB activity instead enhances sensitivity to cytotoxic chemotherapy, thereby exerting a tumor suppressor function. PMID- 22094251 TI - Discovery of a secreted tumor suppressor provides a promising therapeutic strategy for follicular lymphoma. AB - In a recent paper in Cell, Oricchio et al. identify EPHA7 as a tumor suppressor gene residing in the 6q-deleted region in follicular lymphoma. A truncated EPHA7(TR) isoform is secreted by normal B cells, inhibits EPHA2 signaling, and, as a secreted tumor suppressor protein, has potential as a targeted therapeutic polypeptide. PMID- 22094252 TI - CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis. AB - Chromosomal translocations involving the mixed lineage leukemia (MLL) gene lead to the development of acute leukemias. Constitutive HOX gene activation by MLL fusion proteins is required for MLL-mediated leukemogenesis; however, the underlying mechanisms remain elusive. Here, we show that chromobox homolog 8 (CBX8), a Polycomb Group protein that interacts with MLL-AF9 and TIP60, is required for MLL-AF9-induced transcriptional activation and leukemogenesis. Conversely, both CBX8 ablation and specific disruption of the CBX8 interaction by point mutations in MLL-AF9 abrogate HOX gene upregulation and abolish MLL-AF9 leukemic transformation. Surprisingly, Cbx8-deficient mice are viable and display no apparent hematopoietic defects. Together, our findings demonstrate that CBX8 plays an essential role in MLL-AF9 transcriptional regulation and leukemogenesis. PMID- 22094253 TI - Direct signaling between platelets and cancer cells induces an epithelial mesenchymal-like transition and promotes metastasis. AB - Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression toward metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGFbeta and direct platelet-tumor cell contacts synergistically activate the TGFbeta/Smad and NF-kappaB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-kappaB signaling in cancer cells or ablation of TGFbeta1 expression solely in platelets protects against lung metastasis in vivo. Thus, cancer cells rely on platelet-derived signals outside of the primary tumor for efficient metastasis. PMID- 22094254 TI - Altered hematopoietic cell gene expression precedes development of therapy related myelodysplasia/acute myeloid leukemia and identifies patients at risk. AB - Therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) is a major complication of cancer treatment. We compared gene expression in CD34+ cells from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (aHCT) for lymphoma with controls who did not develop t-MDS/AML. We observed altered gene expression related to mitochondrial function, metabolism, and hematopoietic regulation in pre-aHCT samples from patients who subsequently developed t-MDS/AML. Progression to overt t-MDS/AML was associated with additional alterations in cell-cycle regulatory genes. An optimal 38-gene PBSC classifier accurately distinguished patients who did or did not develop t MDS/AML in an independent group of patients. We conclude that genetic programs associated with t-MDS/AML are perturbed long before disease onset, and accurately identify patients at risk for this complication. PMID- 22094255 TI - Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. AB - Cancer cells simultaneously harbor global losses and gains in DNA methylation. We demonstrate that inducing cellular oxidative stress by hydrogen peroxide treatment recruits DNA methyltransferase 1 (DNMT1) to damaged chromatin. DNMT1 becomes part of a complex(es) containing DNMT3B and members of the polycomb repressive complex 4. Hydrogen peroxide treatment causes relocalization of these proteins from non-GC-rich to GC-rich areas. Key components are similarly enriched at gene promoters in an in vivo colitis model. Although high-expression genes enriched for members of the complex have histone mark and nascent transcription changes, CpG island-containing low-expression genes gain promoter DNA methylation. Thus, oxidative damage induces formation and relocalization of a silencing complex that may explain cancer-specific aberrant DNA methylation and transcriptional silencing. PMID- 22094256 TI - A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells. AB - Cyclin D-dependent kinases (CDK4 and CDK6) are positive regulators of cell cycle entry and they are overactive in the majority of human cancers. However, it is currently not completely understood by which cellular mechanisms CDK4/6 promote tumorigenesis, largely due to the limited number of identified substrates. Here we performed a systematic screen for substrates of cyclin D1-CDK4 and cyclin D3 CDK6. We identified the Forkhead Box M1 (FOXM1) transcription factor as a common critical phosphorylation target. CDK4/6 stabilize and activate FOXM1, thereby maintain expression of G1/S phase genes, suppress the levels of reactive oxygen species (ROS), and protect cancer cells from senescence. Melanoma cells, unlike melanocytes, are highly reliant on CDK4/6-mediated senescence suppression, which makes them particularly susceptible to CDK4/6 inhibition. PMID- 22094257 TI - Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis. AB - Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice, and demonstrate that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling. Restoration of Pten expression completely abrogates SCC formation. Reduced levels of GRHL3 and PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC. PMID- 22094258 TI - The NOD-like receptor NLRP12 attenuates colon inflammation and tumorigenesis. AB - NLRP12 is a member of the intracellular Nod-like receptor (NLR) family that has been suggested to downregulate the production of inflammatory cytokines, but its physiological role in regulating inflammation has not been characterized. We analyzed mice deficient in Nlrp12 to study its role in inflammatory diseases such as colitis and colorectal tumorigenesis. We show that Nlrp12-deficient mice are highly susceptible to colon inflammation and tumorigenesis, which is associated with increased production of inflammatory cytokines, chemokines, and tumorigenic factors. Enhanced colon inflammation and colorectal tumor development in Nlrp12 deficient mice are due to a failure to dampen NF-kappaB and ERK activation in macrophages. These results reveal a critical role for NLRP12 in maintaining intestinal homeostasis and providing protection against colorectal tumorigenesis. PMID- 22094259 TI - IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development. AB - Using a mouse model recapitulating the main features of human chronic myelogenous leukemia (CML), we uncover the hierarchy of leukemic stem and progenitor cells contributing to disease pathogenesis. We refine the characterization of CML leukemic stem cells (LSCs) to the most immature long-term hematopoietic stem cells (LT-HSCs) and identify some important molecular deregulations underlying their aberrant behavior. We find that CML multipotent progenitors (MPPs) exhibit an aberrant B-lymphoid potential but are redirected toward the myeloid lineage by the action of the proinflammatory cytokine IL-6. We show that BCR/ABL activity controls Il-6 expression thereby establishing a paracrine feedback loop that sustains CML development. These results describe how proinflammatory tumor environment affects leukemic progenitor cell fate and contributes to CML pathogenesis. PMID- 22094261 TI - A pilot study of preemptive morphine analgesia in preterm neonates: effects on head circumference, social behavior, and response latencies in early childhood. AB - Use of preemptive analgesia in Neonatal Intensive Care Units is recommended for severe and/or invasive procedures. However, the potential long-term consequences of such analgesia, which may be prolonged, are only beginning to be studied. In this pilot study, a subset of subjects previously enrolled in the Neurological Outcomes and Preemptive Analgesia in Neonates (NEOPAIN) trial was assessed at early childhood. These ex-preterm infants (born at 23-32 weeks of gestational age) required intubation within 72 h postpartum and were randomized to receive either preemptive morphine analgesia (maximum of 14 days) or placebo within 8h post-intubation. At 5-7 years of age, neuropsychological outcomes, morphometrics, adaptive behavior, parent-rated behavior, motivation, and short-term memory were measured. Although overall IQ and academic achievement did not differ between the morphine treated (n=14) and placebo (n=5) groups, preemptive morphine analgesia was associated with distinct differences in other outcome variables. Head circumference of morphine treated children was approximately 7% smaller (Cohen'sd: 2.83, effect size large) and body weight was approximately 4% less (Cohen'sd: 0.81, effect size large); however, height did not differ. In the short term memory task (delayed matching to sample), morphine treated children exhibited significantly longer choice response latencies than placebo children (3.86+/-0.33 and 2.71+/-0.24 s, respectively) (p<0.03) and completed approximately 27% less of the task than placebo children (Cohen'sd: 0.96, effect size large). Parents described morphine treated children as having more social problems, an effect specific to creating and maintaining friendships (Cohen'sd: 0.83, effect size large). Despite the small sample size and the preliminary nature of this study, these results are strongly suggestive of long-lasting effects of preemptive morphine analgesia. A larger investigation with more comprehensive assessments of some of these key features will enable a more complete understanding of the relationship between preemptive morphine treatment and long-term neurocognitive, behavioral, and adaptive outcomes. PMID- 22094260 TI - Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia. AB - To identify FDA-approved agents targeting leukemic cells, we performed a chemical screen on two human leukemic cell lines and identified the antimicrobial tigecycline. A genome-wide screen in yeast identified mitochondrial translation inhibition as the mechanism of tigecycline-mediated lethality. Tigecycline selectively killed leukemia stem and progenitor cells compared to their normal counterparts and also showed antileukemic activity in mouse models of human leukemia. ShRNA-mediated knockdown of EF-Tu mitochondrial translation factor in leukemic cells reproduced the antileukemia activity of tigecycline. These effects were derivative of mitochondrial biogenesis that, together with an increased basal oxygen consumption, proved to be enhanced in AML versus normal hematopoietic cells and were also important for their difference in tigecycline sensitivity. PMID- 22094262 TI - Non-invasive prenatal genetic testing: a study of public attitudes. AB - BACKGROUND/OBJECTIVES: Non-invasive prenatal genetic diagnostic (NIPD) tests are being developed using cell-free fetal DNA in the maternal circulation. NIPD tests avoid or reduce the need for invasive diagnostic procedures for conditions like Down syndrome. Discussion of ethical and social implications of these techniques is increasing. We report findings from a study of public attitudes relevant to the introduction of NIPD. A key aim was to examine the range of attitudes relevant to NIPD within a diverse sample. METHODS: Qualitative analysis of written free text 'first responses' to a written neutral description of NIPD as part of a Q-methodology study conducted with a purposive sample of the UK population (n = 71). RESULTS: The majority (63%) of respondents described their first response as positive. However, respondents displayed ambivalence, expressing positive views of individual/medical rationale for NIPD and unease concerning public health rationale and societal implications. Unease related to eugenic reasoning underlying existing prenatal testing, 'too much control' in reproduction, commercial provision, information and support requirements for expanded testing, and limiting the use of testing. CONCLUSIONS: These findings suggest that regulating and monitoring commercial provision of NIPD services, and monitoring introduction and clinical use, are a public preference. PMID- 22094263 TI - Disorders of sexual development in poultry. AB - Sex in birds is determined genetically, as in mammals. However, in birds, female is the heterogametic sex (ZW), while the male is homogametic (ZZ). Although the exact mechanism of avian sex determination is still unclear, genes on one or both of the sex chromosomes must control sexual differentiation of the embryonic gonads into testes or ovaries, and eventually all other sexually dimorphic features. In this review of disorders of sexual development in poultry, we focus upon the gonads and external dimorphisms. Abnormalities of sexual development in poultry can be broadly divided into 2 types: those due to disturbances in sex hormone production by the gonads, and those due to abnormal inheritance of sex chromosomes. Recent studies on gynandromorphic chickens (half male, half female) point to the importance of genetic over hormonal factors in controlling sexual development in fowl. PMID- 22094264 TI - Common fragile sites: mechanisms of instability revisited. AB - Common fragile sites (CFSs) are large chromosomal regions prone to breakage upon replication stress that are considered a driving force of oncogenesis. CFSs were long believed to contain sequences blocking fork progression, thus impeding replication completion and leading to DNA breaks upon chromosome condensation. However, recent studies show that delayed completion of DNA replication instead depends on a regional paucity in initiation events. Because the distribution and the timing of these events are cell type dependent, different chromosomal regions can be committed to fragility in different cell types. These new data reveal the epigenetic nature of CFSs and open the way to a reevaluation of the role played by these sites in the formation of chromosome rearrangements found in tumors from different tissues. PMID- 22094265 TI - Characterizing complex structural variation in germline and somatic genomes. AB - Genome structural variation (SV) is a major source of genetic diversity in mammals and a hallmark of cancer. Although SV is typically defined by its canonical forms (duplication, deletion, insertion, inversion and translocation), recent breakpoint mapping studies have revealed a surprising number of 'complex' variants that evade simple classification. Complex SVs are defined by clustered breakpoints that arose through a single mutation but cannot be explained by one simple end-joining or recombination event. Some complex variants exhibit profoundly complicated rearrangements between distinct loci from multiple chromosomes, whereas others involve more subtle alterations at a single locus. These diverse and unpredictable features present a challenge for SV mapping experiments. Here, we review current knowledge of complex SV in mammals, and outline techniques for identifying and characterizing complex variants using next generation DNA sequencing. PMID- 22094268 TI - Effects of acute stress-induced immunomodulation on TH1/TH2 cytokine and catecholamine receptor expression in human peripheral blood cells. AB - AIMS: There is evidence that psychological stress can modulate immune functions. It has been hypothesized that acute stressors can affect both immune balance (including Th1 and Th2 cytokines) and expression of stress hormone receptors. This study investigated the impact of an acute stressor on gene expressions of glucocorticoid receptor (GR), and beta2-adrenergic receptor (beta2AR) in leukocytes. The effect on T regulatory cells (Treg), regulatory cytokines IL-10 and TGF-beta, Th1 and Th2 cytokines and their receptors IFN-gammaR and IL-4R was also studied. METHOD: Fourteen normal volunteers completed an acute laboratory stressor, and blood samples were collected before, immediately after, and 1, 2, 6 and 24 h after completion of the tasks. Cytokine production and Treg were determined by flow cytometry. Gene expressions of receptors were analyzed by real time PCR. RESULTS: IFN-gamma was increased immediately and 1 h after stressor (p<0.05, respectively) and upregulation of IFN-gammaR mRNA was noted at 2, 6 and 24 h (p<0.01, respectively). IL-10 was decreased at 2 h (p<0.01). There were no significant changes in post-task IL-4R, Treg, or TGF-beta. beta2AR mRNA was increased at 2, 6 and 24 h (p<0.01, respectively). On the other hand, no significant alterations were observed in GR expression. CONCLUSION: An acute stressor increased Th1 cytokine production and its receptor expression. beta2AR but not GR was significantly increased after an acute stressor, which supports the hypothesis that catecholamine-mediated signal pathways in communication with the central nervous and immune systems play a fundamental role in acute stress mediated immune alterations. PMID- 22094269 TI - p24 proteins are required for secretion of Wnt ligands. AB - During development and disease, the exocytosis of signalling molecules, such as Wnt ligands, is essential to orchestrate cellular programs in multicellular organisms. However, it remains a largely unresolved question whether signalling molecules follow specialized transport routes through the exocytic pathway. Here we identify several Drosophila p24 proteins that are required for Wnt signalling. We demonstrate that one of these p24 proteins, namely Opossum, shuttles in the early secretory pathway, and that the Drosophila Wnt proteins are retained in the absence of p24 proteins. Our results indicate that Wnt secretion relies on a specialized anterograde secretion route with p24 proteins functioning as conserved cargo receptors. PMID- 22094270 TI - The ubiquity of consciousness. PMID- 22094271 TI - Algorithms and surrogate markers in translational research. PMID- 22094272 TI - Wnts need a p(assport)24 to leave the ER. PMID- 22094273 TI - Protein phosphatases, from molecules to networks. AB - The third EMBO-sponsored 'Europhosphatases' meeting brought together 180 participants with a wide range of backgrounds and research interests to discuss the current status of research on phosphatases. It became clear at this meeting that the field is very active, and just as diverse as its members. This report highlights some of the transformative research presented at the meeting. PMID- 22094274 TI - Pol II caught speeding by single gene imaging. PMID- 22094275 TI - Will we wake up to biodiversity? PMID- 22094276 TI - Dilated cardiomyopathy: an unexpected complication of rapidly conducted atrial flutter in the Wolff-Parkinson-White syndrome. AB - This report describes a 34-year-old male with the Wolff-Parkinson-White syndrome who presented with the unusual finding of a tachyarrhythmia-induced cardiomyopathy secondary to atrial flutter with 1:1 conduction through a left lateral accessory pathway. Catheter ablation of the accessory connection resulted in complete normalization of cardiac function. PMID- 22094277 TI - Synthesis and characterization of 5-alkoxycarbonyl-4-hydroxymethyl-5-alkyl pyrroline N-oxide derivatives. AB - The syntheses, analytical properties, and spin trapping behavior of four novel EMPO derivatives, namely 5-ethoxycarbonyl-4-hydroxymethyl-5-methyl-pyrroline N oxide (EHMPO), 5-ethoxycarbonyl-5-ethyl-4-hydroxymethyl-pyrroline N-oxide (EEHPO), 4-hydroxymethyl-5-methyl-5-propoxycarbonyl-pyrroline N-oxide (HMPPO), and 4-hydroxymethyl-5-methyl-5-iso-propoxycarbonyl-pyrroline N-oxide (HMiPPO), towards different oxygen- and carbon-centered radicals are described. PMID- 22094278 TI - Development of ligands at gamma-aminobutyrric acid type A (GABAA) receptor subtype as new agents for pain relief. AB - The identification of compounds with selective anxiolytic-like effects, exerted through the benzodiazepine site on gamma-aminobutyric acid type A (GABA(A)) receptors, and that show pronounced antihyperalgesia in several pain models, has oriented research towards the development of new agents for the relief of pain. Starting from our previously reported ligands at the benzodiazepine site on GABA(A) receptors showing selective anxiolytic-like effects, we have designed new compounds with the aim of identifying those devoid of the typical side effects of the classical benzodiazepines. Our preliminary results indicate that compounds 4, 10(+/-) and 11 have a very promising antihyperalgesic profile in different animal pain models (peripheral mono-neuropathy, STZ-induced hyperalgesia). In particular 11 exhibits high potency since it exerted its protective effect starting from the dose of 3mg/kg po, after single injection. PMID- 22094279 TI - Design, synthesis, and biological evaluation of 4-phenylpyrrole derivatives as novel androgen receptor antagonists. AB - A series of 4-phenylpyrrole derivatives D were designed, synthesized, and evaluated for their potential as novel orally available androgen receptor antagonists therapeutically effective against castration-resistant prostate cancers. 4-Phenylpyrrole compound 1 exhibited androgen receptor (AR) antagonistic activity against T877A and W741C mutant-type ARs as well as wild-type AR. An arylmethyl group incorporated into compound 1 contributed to enhancement of antagonistic activity. Compound 4n, 1-{[6-chloro-5-(hydroxymethyl)pyridin-3 yl]methyl}-4-(4-cyanophenyl)-2,5-dimethyl-1H-pyrrole-3-carbonitrile exhibited inhibitory effects on tumor cell growth against the bicalutamide-resistant LNCaP cxD2 cell line as well as the androgen receptor-dependent JDCaP cell line in a mouse xenograft model. These results demonstrate that this series of pyrrole compounds are novel androgen receptor antagonists with efficacy against prostate cancer cells, including castration-resistant prostate cancers such as bicalutamide-resistant prostate cancer. PMID- 22094280 TI - Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases. AB - The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds, whereas the influence of substituents of the amide residue is less relevant. The para-hydroxy substituted analog was found to be the most potent inhibitor in this series with a K(i)-value of 35.7 MUM at the Dengue and 44.6 MUM at the West Nile virus protease. The aprotinin competition assay demonstrates a direct interaction of the inhibitor molecule with active centre of the Dengue virus protease. The target selectivity was studied in a counterscreen with thrombin and found to be 2.8:1 in favor of DEN protease and 2.3:1 in favor of WNV protease, respectively. PMID- 22094281 TI - Vaccine shortages and suspect online pharmacy sellers. AB - Vaccines represent half the products on the FDA Biologics Product Shortages list. As a result, providers and patients may purchase them online, a process rife with patient safety risks. We examined vaccine online availability by assessing up to 5 identified online sellers. We determined if sites were accredited by the National Association of Boards of Pharmacy (NABP) VIPPS program, listed as US or international, employed social media linking to suspect online pharmacies, and if they were on the NABP Not Recommended list. All vaccines were advertised by online pharmacies and through data aggregation and social media sites, none were VIPPS-accredited, and most were on the NABP Not Recommended list. We found some online sellers advertising vaccines as over-the-counter. We extended our analysis to WHO Essential Medicines List vaccines and found all are also available online from suspect, non-VIPPS accredited sellers. Stakeholders should be aware of these online patient safety dangers. PMID- 22094282 TI - Pertussis vaccination in infancy lowers the incidence of pertussis disease and the rate of hospitalisation after one and two doses: analyses of 10 years of pertussis surveillance. AB - OBJECTIVES: Shortly after pertussis vaccination was reintroduced in Sweden in 1996, an intensified pertussis disease surveillance programme was set up. In this study, we report on in-depth analyses of age-dose-number-specific incidences and the rate of pertussis hospitalisation for children with no, 1 or 2 doses of an acellular pertussis vaccine before pertussis disease. Vaccine coverage, the timeliness of childhood vaccination and the effect of later than scheduled pertussis vaccination(s) are also examined. STUDY DESIGN: Children with notified laboratory-confirmed (culture or PCR) pertussis disease were evaluated among the surveillance population of about 1 million infants, born between 1996 and 2007 and followed for pertussis disease from October 1997 to December 2007, for nearly 6 million person-years. Birth and vaccination dates of the diseased children are known from the surveillance programme. To estimate denominators of the age-dose number-specific pertussis incidences, we used birth and vaccination dates from a vaccine trial with more than 72,000 infants combined with national pertussis vaccine coverage data for children in the surveillance population. RESULTS: For infants from 3 to <5 months of age, the incidence of pertussis disease with at least 14 days of cough decreased from 264/100,000 for unvaccinated infants to 155/100,000 for infants with one dose of a pertussis vaccine prior to onset of the disease. In the age range 5 to <12 months, the age-dose specific incidences were 526, 95, and 24/100,000 for infants with no, 1 and 2 doses, respectively. The rate of hospitalisation for infants with 1 dose of a pertussis vaccine prior to onset of the disease was significantly lower than for unvaccinated infants of the same age. For many infants, there is a delay in administration of the vaccine doses according to the regular 3-5-12 month schedule (which has been the case for many years). Hypothetically, if all infants had been vaccinated exactly on schedule, we would expect about 28% fewer pertussis cases with at least 14 days of cough and 38% fewer hospitalisations due to pertussis, of cases possible to influence by vaccinations on schedule. CONCLUSION: Pertussis vaccination had a significant effect among infants already after the first dose. This is particularly important for premature infants and infants with severe respiratory and cardiac diseases. A moderate decrease in the incidence of pertussis disease in infants and rate of hospitalisation could be expected if primary vaccinations were carried out closer to the scheduled time than is currently the practice in Sweden. PMID- 22094283 TI - Pneumococcal sequence type replacement among American Indian children: a comparison of pre- and routine-PCV7 eras. AB - BACKGROUND: Multi-locus sequence typing (MLST) of pneumococcal isolates collected during an efficacy trial of the 7-valent pneumococcal conjugate vaccine (PCV7) among Navajo and White Mountain Apache children from 1998 to 2000 showed a non differential expansion of pre-existing sequence types (STs) and only one capsule switching event in the PCV7-randomized communities. PCV7 was introduced as a routine infant vaccine in October 2000. We assessed variability in PCV7 effectiveness and mechanisms of ST replacement after prolonged routine PCV7 use. METHODS: We applied MLST to 267 non-vaccine type pneumococcal carriage and invasive disease isolates from Navajo and White Mountain Apache children from 2006 to 2008, and compared them to those from 1998 to 2000. Microarray was used to confirm capsule switching events. RESULTS: The primary mechanism of ST replacement among Navajo and White Mountain Apache children was expansion of existing STs, although introduction of new STs was an important secondary mechanism. ST199, a majority being serotype 19A, was the most common ST in both eras. Only ST193 (serotype 21) was preferentially expanding in the PCV7 era. Three examples of capsule switching were identified. No variability in vaccine effectiveness by ST was observed. CONCLUSION: We did not observe an influence of ST on PCV7 serotype-specific effectiveness, although some STs may be favored in replacement. PMID- 22094284 TI - Aberrant expression of serum miRNAs in schizophrenia. AB - The circulating miRNAs are sufficiently stable and detectable to serve as clinical biomarkers as recent studies have revealed that the aberrant expression of circulating miRNAs can directly reflect disease status. Based on the analysis of the data (using miRanda software, TargetScan software and SOLID high throughput sequencing) obtained from the literature, Schizophrenia Gene database, NCBI database, the quantification of the nine miRNAs in the serum samples of 115 patients suffering from schizophrenia and 40 healthy individuals using qRT-PCR and semi-nested qRT-PCR was conducted. The results suggested that the miR-181b, miR-219-2-3p, miR-346, miR-195, miR-1308, miR-92a, miR-17, miR-103 and let-7g are the key players to reflect the schizophrenia illnesses status and may serve as candidate biomarkers for diagnosis of schizophrenia. In addition, we also found that the risperidone improved the serum miR-346 level of schizophrenia significantly, and therefore may not be an effective drug in regulating serum miR 346 level of schizophrenia. Furthermore, the expression level of serum miRNAs levels and schizophrenia patients were regardless of family history subtypes, ages, and gender. Collectively, these findings suggested that the serum miRNAs have strong potential to reflect schizophrenia disease status. To the best of our knowledge, this is the first report demonstrating the analysis of the circulating miRNAs in schizophrenia. PMID- 22094285 TI - Clinicopathological correlation of Kruppel-like factor 5 and matrix metalloproteinase-9 expression and cartilage degeneration in human osteoarthritis. AB - The present study was designed to investigate the clinicopathological correlation between the expression of KLF5 and MMP-9, which are associated with extracellular matrix degradation and cartilage degeneration in human knee osteoarthritis (OA). Tibiofemoral joint samples from 20 patients with OA, treated with surgery alone, were divided into two groups: 0=no change (NC, n=17), and severe changes with a higher mean score (>= 3) (SC, n=29). The latter group contains samples with severe damages in cartilages and subchondral bones at medial tibial plateaux. The expression of the proteins was detected by immunofluorescence and quantitative RT PCR, respectively. Neurovascular invasion was evaluated by protein gene product (PGP) 9.5 and CD34-positive staining and scanning electron microscopy, respectively. Safranin O staining showed that the sections from the SC group had increased cartilage degeneration. The number of vascular invasions in the SC group (16/29, 55.2%) was higher than that in NC controls (2/17, 11.7%, P<0.05). The expression of KLF5 and MMP-9 increased, and was co-localized in the same cells of SC cartilages. The severity of cartilage degeneration and vascular invasion was associated with upregulation of the two protein expressions and was significantly different between SC and NC samples (P<0.05). Taken together, the expression of KLF5 and MMP-9 may be involved in cartilage degeneration, contributing to human OA. PMID- 22094286 TI - Destiny in your own hands--does a positive family history matter in the prevention of type 2 diabetes? PMID- 22094287 TI - Amorphous silica nanoparticles do not induce cytotoxicity, cell transformation or genotoxicity in Balb/3T3 mouse fibroblasts. AB - Although amorphous silica nanoparticles (aSiO(2)NPs) are believed to be non-toxic and are currently used in several industrial and biomedical applications including cosmetics, food additives and drug delivery systems, there is still no conclusive information on their cytotoxic, genotoxic and carcinogenic potential. For this reason, this work has investigated the effects of aSiO(2)NPs on Balb/3T3 mouse fibroblasts, focusing on cytotoxicity, cell transformation and genotoxicity. Results obtained using aSiO(2)NPs, with diameters between 15 nm and 300 nm and exposure times up to 72 h, have not shown any cytotoxic effect on Balb/3T3 cells as measured by the MTT test and the Colony Forming Efficiency (CFE) assay. Furthermore, aSiO(2)NPs have induced no morphological transformation in Balb/3T3 cells and have not resulted in genotoxicity, as shown by Cell Transformation Assay (CTA) and Micronucleus (MN) assay, respectively. To understand whether the absence of any toxic effect could result from a lack of internalization of the aSiO(2)NPs by Balb/3T3 cells, we have investigated the uptake and the intracellular distribution following exposure to 85 nm fluorescently-labelled aSiO(2)NPs. Using fluorescence microscopy, it was observed that fluorescent aSiO(2)NPs are internalized and located exclusively in the cytoplasmic region. In conclusion, we have demonstrated that although aSiO(2)NPs are internalized in vitro by Balb/3T3 mouse fibroblasts, they do not trigger any cytotoxic or genotoxic effect and do not induce morphological transformation, suggesting that they might be a useful component in industrial applications. PMID- 22094288 TI - Genotoxicity of inhaled nanosized TiO(2) in mice. AB - In vitro studies have suggested that nanosized titanium dioxide (TiO(2)) is genotoxic. The significance of these findings with respect to in vivo effects is unclear, as few in vivo studies on TiO(2) genotoxicity exist. Recently, nanosized TiO(2) administered in drinking water was reported to increase, e.g., micronuclei (MN) in peripheral blood polychromatic erythrocytes (PCEs) and DNA damage in leukocytes. Induction of micronuclei in mouse PCEs was earlier also described for pigment-grade TiO(2) administered intraperitoneally. The apparent systemic genotoxic effects have been suggested to reflect secondary genotoxicity of TiO(2) due to inflammation. However, a recent study suggested that induction of DNA damage in mouse bronchoalveolar lavage (BAL) cells after intratracheal instillation of nanosized or fine TiO(2) is independent of inflammation. We examined here, if inhalation of freshly generated nanosized TiO(2) (74% anatase, 26% brookite; 5 days, 4 h/day) at 0.8, 7.2, and (the highest concentration allowing stable aerosol production) 28.5 mg/m(3) could induce genotoxic effects in C57BL/6J mice locally in the lungs or systematically in peripheral PCEs. DNA damage was assessed by the comet assay in lung epithelial alveolar type II and Clara cells sampled immediately following the exposure. MN were analyzed by acridine orange staining in blood PCEs collected 48 h after the last exposure. A dose-dependent deposition of Ti in lung tissue was seen. Although the highest exposure level produced a clear increase in neutrophils in BAL fluid, indicating an inflammatory effect, no significant effect on the level of DNA damage in lung epithelial cells or micronuclei in PCEs was observed, suggesting no genotoxic effects by the 5-day inhalation exposure to nanosized TiO(2) anatase. Our inhalation exposure resulted in much lower systemic TiO(2) doses than the previous oral and intraperitoneal treatments, and lung epithelial cells probably received considerably less TiO(2) than BAL cells in the earlier intratracheal study. PMID- 22094289 TI - Mequindox induced cellular DNA damage via generation of reactive oxygen species. AB - Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using gamma-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS. PMID- 22094290 TI - Assessing the genotoxic potentials of roxarsone in V79 cells using the alkaline Comet assay and micronucleus test. AB - Until recently, knowledge about the genotoxicity of roxarsone in vitro or in vivo was limited. This study assessed the genotoxicity of roxarsone in an in vitro system. Roxarsone was tested for potential genotoxicity on V79 cells by a Comet assay and a micronucleus (MN) test, exposing the cells to roxarsone (1-500 MUM) and to sodium arsenite (NaAsO2, 20 MUM) solutions for 3-48 h. Roxarsone was found to be cytotoxic when assessed with a commercial cell counting kit (CCK-8) used to evaluate cell viability, and moderately genotoxic in the Comet assay and micronucleus test used to assess DNA damage. The Comet metrics (percentages TDNA, TL, TM) increased significantly in a time- and concentration-dependent manner in roxarsone-treated samples compared with PBS controls (P<0.05), while the data from samples treated with 20 MUM NaAsO2 were comparable to those from 500 MUM roxarsone-treated samples. The MN frequency of V79 cells treated with roxarsone was higher than that in the negative control but lower than the frequency in cells treated with 20 MUM NaAsO2. A dose- and time-dependent response in MN induction was observed at 10, 50, 100 and 500 MUM doses of roxarsone after 12-48 h exposure time. The DNA damage in V79 cells treated with 500 MUM roxarsone was similar to cells exposed to 20 MUM NaAsO2. The uptake of cells was correlated with the DNA damage caused by roxarsone. This investigation depicts the genotoxic potentials of roxarsone to V79 cells, which could lead to further advanced studies on the genotoxicity of roxarsone. PMID- 22094291 TI - Additive and interactive effects of nutrient classes on longevity, reproduction, and diet consumption in the Queensland fruit fly (Bactrocera tryoni). AB - Insect lifespan is often closely linked to diet, and diet manipulations have been central to studies of ageing. Recent research has found that lifespan for some flies is maximised on a very low yeast diet, but once all yeast is removed, lifespan drops precipitously. Although effects of yeast availability on lifespan are commonly interpreted in terms of protein, yeast is a complex mix of nutrients and provides a rich source of vitamins, minerals and sterols. Elucidating which components of yeast are involved in this lifespan drop provides insights into more specific nutritional requirements and also provides a test for the commonplace interpretation of yeast in terms of protein. To this end, we fed Queensland fruit flies (Bactrocera tryoni) one of eight experimental diets that differed in the nutrient group(s) found in yeast that were added to sucrose: none, vitamins, minerals, amino acids, cholesterol, vitamin+mineral+cholesterol (VMC), vitamin+mineral+cholesterol+amino acids (VMCA), and yeast. We measured survival rates and egg production in single sex and mixed sex cages, as well as nutrient intake of individual flies. We found that the addition of minerals increased lifespan of both male and female flies housed in single sex cages by decreasing baseline mortality. The addition of just amino acids decreased lifespan in female flies; however, when combined with other nutrient groups found in yeast, amino acids increased lifespan by decreasing both baseline mortality and age-specific mortality. Flies on the yeast and VMCA diets were the only ones to show significant egg production. We conclude that the drop in lifespan observed when all yeast is removed is explained by missing micronutrients (vitamins, minerals and cholesterol) as well as the absence of protein in females, whereas minerals alone can explain the pattern for males. These results indicate a need for caution when interpreting effects of dietary yeast as effects of protein. PMID- 22094292 TI - A method to evaluate profilometric tooth wear measurements. AB - OBJECTIVES: To test the accuracy of measurements of tooth wear using a non contacting laser profilometer (NCLP) and surface matching software. METHODS: The accuracy and repeatability of the NCLP and software in measuring length was assessed by repeatedly scanning a calibrated 25 mm engineering steel gage block. Volumetric measurements were assessed after scanning commercially pure titanium frustums of varying volume. The accuracy and repeatability of the systems in measuring step height and volume after surface matching were assessed using a custom built model with cemented engineering slip gages and cemented onlays of super-plastically formed titanium. The overall effect on the uncertainty of measurement of repeated superimpositions of the same cast, repeated impressions of the same patient and using step-over distances smaller than the laser spot size were also quantified. RESULTS: The accuracy and repeatability were 1.3 MUm and 1.6 MUm in measuring length. The system was accurate for volumetric measurement with coefficients of variation <5%. Measurements using the model with cemented engineering slip gages and cemented super-plastically formed titanium onlays varied slightly (23.07 MUm and 1.6 mm(3)). Scanning and superimposing the same model introduced mean error of 2.7 MUm (SD=0.7). Scanning and superimposing separate casts from repeated impressions of a patient introduced mean error of 14.8 MUm (SD=2.8). Decreasing step-over distances reduced measurement error (p<0.05). SIGNIFICANCE: The methodologies described here served to assess sources of error in tribology studies using surface mapping and surface matching technologies. The results optimized data interpretation. Study supported by Guy's and St. Thomas' Charity and the Royal College of Surgeons of England. PMID- 22094293 TI - The different impact of a high fat diet on dystrophic mdx and control C57Bl/10 mice. AB - The absence of functional dystrophin protein in patients with Duchenne muscular dystrophy (DMD) and dystrophic mdx mice leads to fragile myofibre membranes and cycles of myofibre necrosis and regeneration. It is proposed that both DMD patients and mdx mice have an altered metabolism and impaired energy status and that nutritional supplementation may reduce the severity of dystropathology. This research compares the in vivo responses of dystrophic mdx and normal control C57Bl/10 mice to a high protein (50%) or a high fat (16%) diet. Consumption of a high protein diet had minimal effects on the body composition or muscle morphology in both strains of mice. In contrast, differences between the strains were seen in response to the high fat diet; this response also varied between mdx mice aged <24 weeks, and mdx mice aged 24 - 40 weeks. C57Bl/10 mice demonstrated many negative side effects after consuming the high fat diet, including weight gain, increased body fat, and elevated inflammatory cytokines. In contrast, after consuming the high fat diet for 16 weeks the mdx mice (< 24 weeks) remained lean with minimal fat deposition and were resistant to changes in body composition. These results support the proposal that energy metabolism in dystrophic mdx mice is altered compared to normal C57Bl/10 mice and this enables the mdx mice to better metabolise the high fat diet and avoid fat deposition. However, older mdx mice (24 - 40-week-old), with increased energy intake, exhibited some mild adverse effects of a high fat diet but to a far lesser extent than age-matched C57Bl/10 mice. Benefits of the high fat diet on dystrophic muscles of young mice were demonstrated by the significantly increased running ability (km) of voluntarily exercised mdx mice and significantly reduced myofibre necrosis in 24 week-old sedentary mdx mice. These novel data clearly identify an 'altered' response to a high fat diet in dystrophic mdx compared to normal C57Bl/10 mice. Our data indicate that the high fat diet may better meet the energy needs of mdx mice to reduce muscle damage and improve muscle function. PMID- 22094294 TI - Increased risk of asthma and atopic dermatitis in perinatally HIV-infected children and adolescents. AB - The incidence of asthma and atopic dermatitis (AD) was evaluated in HIV-infected (n = 451) compared to HIV-exposed (n = 227) but uninfected (HEU) children and adolescents by abstraction from clinical charts. Asthma was more common in HIV infected compared to HEU children by clinical diagnosis (25% vs. 20%, p = 0.101), by asthma medication use, (31% vs. 22%, p = 0.012), and by clinical diagnosis and/or medication use, (34% vs. 25%, p = 0.012). HIV-infected children had a greater risk of asthma compared to HEU children (HR = 1.37, 95% CI: 1.01 to 1.86). AD was more common in HIV-infected than HEU children (20% vs. 12%, p = 0.009)) and children with AD were more likely to have asthma in both cohorts (41% vs. 29%, p = 0.010). HIV-infected children and adolescents in this study had an increased incidence of asthma and AD, a finding critical for millions of HIV infected children worldwide. PMID- 22094295 TI - A rare case of recurrent fetal goiter. AB - We report the case of fetal goiter which occurred in two consecutive pregnancies in the same patients. The first one, due to too late diagnosis and no intrauterine treatment, contributed to the immediate postnatal death of the newborn; the second one was properly diagnosed at 19 weeks and then effectively treated prenatally which allowed to avoid the fatal complications for the fetus and the newborn. PMID- 22094296 TI - Ketorolac therapy for the prevention of acute pseudophakic cystoid macular edema: a systematic review. AB - To assess the effectiveness of ketorolac vs control for prevention of acute pseudophakic cystoid macular edema (CME). The following databases were searched: Medline (1950-June 11, 2011), The Cochrane Library (Issue 2, 2011), and the TRIP Database (up to 11 June 2011), using no language or other limits. Randomized controlled clinical trials (RCTs) were included that consisted of patients with acute pseudophakic cystoid macular edema, those comparing ketorolac with control, and those having at least a minimum follow-up of 28 days. In the four RCTs evaluating ketorolac vs control, treatment with ketorolac significantly reduced the risk of CME development at the end of treatment (~ 4 weeks) compared to control (P=0.008; 95% confidence interval (0.03-0.58)). When analyzed individually, each individual study was statistically nonsignificant in its findings with the exception of one study. When the pooled relative risk was calculated, the large sample size of this systematic review led to overall statistical significance, which is attributable to the review's large sample size and not to the individual studies themselves. In this systematic review of four RCTs, two of which compared ketorolac with no treatment and two of which evaluated ketorolac vs placebo drops, treatment with ketorolac significantly reduced the risk of developing CME at the end of ~ 4 weeks of treatment compared with controls. These results, however, should be interpreted with caution considering the paucity of large randomized clinical trials in the literature. PMID- 22094297 TI - The incidence and distribution of iatrogenic retinal tears in 20-gauge and 23 gauge vitrectomy. AB - PURPOSE: The development of 23-gauge vitrectomy surgery has many benefits including a reduction in surgical time and faster postoperative rehabilitation; however, some have suggested that the complication rate is higher. To assess this we compared the incidence and distribution of iatrogenic retinal tears in 20- and 23-gauge surgery. METHODS: Fifty consecutive 23-gauge and 50 consecutive 20-gauge vitrectomy cases were selected; eyes with a history of previous vitreoretinal surgery were excluded. All surgery was performed by two surgeons (JL and RN). Entry-site breaks (ESB) were defined as any new vitreoretinal abnormality occurring within 1 clock hour of an entry site for which treatment with cryotherapy was deemed necessary. Data were collected by retrospective case note review. Statistical analysis was carried out using Fisher's exact and chi(2) tests. RESULTS: ESB occurred in 24% (12/50) of cases in the 20-gauge group compared with 8% (4/50) in the 23-gauge group (P = 0.03); 88% (14/16) occurred superiorly on the same side as the surgeons' dominant hand. Iatrogenic breaks recorded elsewhere indicated an increased incidence in the 20-gauge group (9/50 compared with 6/50 in 23-gauge) but this did not achieve significance; the most common position was at 6 o'clock. CONCLUSIONS: 23-Gauge vitrectomy is associated with significantly fewer ESB when compared with conventional 20-gauge vitrectomy. The incidence of other iatrogenic breaks did not appear to be significantly different between the two groups. PMID- 22094298 TI - The willingness of patients presenting with advanced glaucoma to participate in a trial comparing primary medical vs primary surgical treatment. AB - AIM: The aim of this study is to examine the attitudes of patients, who presented with advanced glaucoma in at least one eye, to participation in a randomised prospective trial comparing primary medical treatment with primary surgical treatment for advanced glaucoma. METHODS: Patients who had presented with advanced glaucoma (>15 dB loss mean deviation on Humphrey visual field testing) in at least one eye were asked to participate. Five focus groups comprising of 4 8 patients and consisting of 29 patients in total were undertaken. The group interviews were conducted by two experienced qualitative researchers, an ophthalmic clinician was present to clarify technical issues. The focus group discussions were taped and transcribed in full, and analysed through a process of familiarisation, open (inductive) coding, theme generation, theme refinement, and thematic mapping. RESULTS: Three overarching themes were identified: (1) the extent of patients' knowledge, (2) anxieties about surgery, and (3) concerns about compromised care due to trial involvement; these themes were further classified into eight sub-themes. CONCLUSIONS: Patients' willingness to participate in randomised clinical studies is significantly connected to their level of comprehension and insight about the medical condition, its treatment, and the research process; misunderstandings about any of these aspects may act as a significant barrier to trial recruitment. Recruitment rates for future randomised trials may be enhanced by ensuring that patients have full and accurate information about the treatment alternatives, and that uncertainty exists for best patient outcomes between treatment options, and reassuring potential participants that the research process, in particular randomisation, will not compromise clinical care. PMID- 22094299 TI - Diagnosis of infectious diseases of the eye. AB - Specific therapy of ocular infections often requires etiological diagnosis that is a combined effect of observation of characteristic clinical features and microbiological investigations. Clinical impression is central to guiding the laboratory investigation, and the aim of laboratory investigation is to confirm or rule out the clinical diagnosis. However, clinical features may vary considerably, and no one clinical feature may be pathognomonic of a particular pathogen. In addition, there may be a racial, geographical, and climatic difference in the distribution and type of causative agents associated with infections. Ophthalmologists have at their disposal in vivo and in vitro methods of diagnosis of ocular infections. The expertise of the clinician and the microbiologist along with the facilities available, determine the success with accurate diagnosis. A wide range of conventional and molecular techniques are available that not only provide rapid diagnosis for known common infections but have the potential to bring to the fore unknown organisms that may be associated with ocular infections. PMID- 22094300 TI - Humphrey visual field findings in hydroxychloroquine toxicity. AB - PURPOSE: To analyze Humphrey visual field (HVF) findings in hydroxychloroquine (HCQ) retinal toxicity. METHODS: HVF tests were interpreted retrospectively in this observational case series of 15 patients with HCQ toxicity. Patients seen at Lahey Clinic were identified by diagnosis coding search. Patients with age related macular degeneration or glaucoma with visual field loss were excluded. HVFs done before the diagnosis were analyzed to see if earlier diagnosis could have been possible. RESULTS: A total of 66 HVFs were reviewed and categorized. Some abnormalities were subtle. Paracentral defects were seen on 10-2 tests whereas 24-2 tests, due to their compressed scale, showed central changes. The abnormalities were often more obvious on pattern deviation rather than the gray scale. Of those patients with prior HVFs available for review, 50% showed HVF abnormalities typical of HCQ toxicity present several months or years before diagnosis. HVF changes preceded fundus changes in nine patients. CONCLUSION: HVF abnormalities indicating HCQ toxicity vary depending on the specific HVF test performed. Clinicians need to be aware of the subtle nature of HVF changes in early toxicity. PMID- 22094301 TI - Contact lens disinfecting solutions antibacterial efficacy: comparison between clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus. AB - PURPOSE: To evaluate the disinfectant properties of the three multipurpose contact lens disinfecting solutions available in Iran, against clinical isolates and the standard ISO ATCC strains of Pseudomonas aeruginosa and Staphylococcus aureus, based on the international organization for standardization (ISO) 14729 guidelines. METHODS: Three multipurpose solutions that were tested were ReNu Multiplus, Solo Care Aqua and All-Clean Soft. The test solutions were challenged with clinical isolates and the standard strains of P. aeruginosa(ATCC 9027) and S. aureus(ATCC 6538), based on the ISO Stand-alone procedure for disinfecting products. Solutions were sampled for surviving microorganisms at manufacturer's minimum recommended disinfection time. The number of viable organisms was determined and log reductions calculated. RESULTS: All of the three test solutions in this study provided a reduction greater than the required mean 3.0 logarithmic reduction against the recommended standard ATCC strains of P. aeruginosa and S. aureus. Antibacterial effectiveness of Solo Care Aqua and All Clean Soft against clinical isolates of P. aeruginosa and S. aureus were acceptable based on ISO 14729 Stand-alone test. ReNu MultiPlus showed a minimum acceptable efficacy against the clinical isolate of S. aureus, but did not reduce the clinical isolate by the same amount. CONCLUSIONS: Although the contact lens disinfecting solutions meet/exceed the ISO 14729 Stand-alone primary acceptance criteria for standard strains of P. aeruginosa and S. aureus, their efficacy may be insufficient against clinical isolates of these organisms. PMID- 22094302 TI - Ophthalmic features of Friedreich ataxia. AB - PURPOSE: To describe ocular abnormalities in patients with Friedreich ataxia (FRDA). METHODS: Patients diagnosed with FRDA by genetic analysis were invited to participate in a prospective cohort. The patients included underwent an extensive ophthalmologic examination, including low-contrast Sloan letter charts test and retinal nerve fiber layer (RNFL) thickness analysis by optical coherence tomography (OCT). RESULTS: Twenty-three patients agreed to participate. In all, 19 patients (83%) had a visual acuity of at least 0.8 in both eyes. Fundus examination showed diffuse optic nerve pallor in four patients. However, OCT showed a decreased mean peripapillary RNFL thickness in all but three adult cases and one teenager. The RNFL thickness was found to have a positive correlation with visual acuity (P=0.001) and contrast sensitivity (P=0.001) and a negative correlation with time elapsed from diagnosis (P=0.001). CONCLUSIONS: OCT and low contrast test sensitivity show that the visual pathway is affected in FRDA. However, in most patients there is no significant visual impairment. In a small proportion of patients visual acuity declines with disease progression. This study provides a better understanding of the ophthalmic features of FRDA. PMID- 22094303 TI - Individualised patient care as an adjunct to standard care for promoting adherence to ocular hypotensive therapy: an exploratory randomised controlled trial. AB - PURPOSE: To evaluate the impact of individualised patient care, as an adjunct to standard care, on adherence to ocular hypotensive therapy. METHODS: A two-arm, single-masked exploratory randomised controlled trial recruited patients newly prescribed ocular hypotensive therapy. The intervention involved an individual assessment of health-care needs and beliefs and a 1-year follow-up period according to need. The primary outcome was refill adherence, measured by collating prescription and dispensing data for 12 months. Secondary outcomes included self-reported adherence, glaucoma knowledge, beliefs about illness and medicines, quality of care, intraocular pressure (IOP) fluctuation, and changes in clinical management assessed at 12 months. The strength of the intervention was measured following withdrawal by reviewing clinical outcomes for a further 12 months. RESULTS: In all, 127 patients were recruited (91% response rate). Intervention-arm patients collected significantly more prescriptions than control arm patients. Self-report adherence was significantly better in the intervention arm for patients who forgot drops and those who intentionally missed drops. The intervention group demonstrated significantly more glaucoma knowledge, expressed a significantly stronger belief in the necessity of eye drops and believed that they had more personal control over managing their condition. Control-arm patients had more IOP fluctuation and changes in clinical management. However, this finding only reached significance at 24 months. CONCLUSION: Modelling patient care according to health-care needs and beliefs about illness and medicines can have a significant impact on improving adherence to therapy for this patient group, with the potential benefit of improving clinical outcomes. PMID- 22094305 TI - Predicting death in massive hemoptysis. PMID- 22094304 TI - Total protein concentration and T-cell suppression activity of aqueous humour before and after penetrating keratoplasty. AB - PURPOSE: We wished to determine whether immune privilege parameters assayed in aqueous humour (AqH) are relevant to the fate of penetrating keratoplasty (PK) in humans. METHODS: AqH was collected in 28 patients before PK (prospective cohort), in 6 patients with no history of graft rejection undergoing cataract surgery after PK (acceptors), in another 6 patients undergoing treatment of an acute endothelial immune reaction (rejectors), and in 65 controls undergoing uncomplicated cataract extraction. AqH was tested for total protein concentration and the ability to suppress T-cell activation. RESULTS: AqH protein concentrations of acceptors and rejectors post-PK were elevated (2.7 +/- 0.8 and 2.7 +/- 0.7 mg/ml, respectively) compared with pre-PK AqH level and cataract controls (1.0 +/- 0.1 mg/ml, P = 0.01). All AqH samples suppressed T-cell activation, irrespective of source and timing of AqH removal. CONCLUSION: Assays of immune privilege markers in AqH suggest that PK surgery may result in a sustained loss of integrity of the blood-aqueous barrier. Although trends were evident, values of immune privilege markers determined pre- and post-PK were not statistically significantly different between the study groups. However, further prospective studies determining additional immune privilege markers have to be conducted in order to find out whether these markers might serve as predictive parameters for immune reactions following PK. PMID- 22094306 TI - Efficacy, nephrotoxicity and ototoxicity of aminoglycosides, mathematically modelled for modelling-supported therapeutic drug monitoring. AB - Therapeutic drug monitoring (TDM) of aminoglycosides has been a topic during the last thirty years. There is a tendency that - because of the once-daily regimen - TDM is considered not necessary anymore. Although once daily dosing has the potential for decreased toxicity, long-term usage can cause severe nephro- and ototoxicity. Furthermore, inadequate plasma concentrations can lead to treatment failure. This work is devoted to the development and application of the first mathematical model of aminoglycosides, which simulates in relation to the pharmacokinetics both their effects on bacteria as well as their nephrotoxicity and cochleotoxicity. Our software system is suitable for TDM. Based on theoretical considerations, a multi-compartment mathematical model in a numerical program in Matlab is derived that incorporates the antimicrobial effects of aminoglycosides, the saturable and active uptake into kidney cells, the reversible nephrotoxicity and the irreversible cochleotoxicity. Using fictitious person data, and an assumed pharmacokinetic and dynamic parameter set obtained from the literature, we simulated the drug concentrations, antibacterial effects, and toxicity over time in virtual patients to illustrate the benefits of optimized, efficacious dosage regimens that minimize (acceptable) nephro- and auditory ototoxicity. Our model confirms that extended-interval dosing seems the most appropriate to achieve this goal. By this manner, the present mathematical model contributes to an increase in our knowledge of how to obtain an optimized dosing strategy for individual patients. With the developed program, we are able to demonstrate that optimal aminoglycoside dosing still needs a sophisticated system of TDM. PMID- 22094307 TI - Effects of early postnatal allopregnanolone administration on elevated plus maze anxiety scores in adult male Wistar rats. AB - BACKGROUND/AIMS: Recent findings suggest that neurosteroids are involved in brain development. The present study focused on the long-term effects of developmentally altered allopregnanolone (AlloP) levels on anxiety-like behavior in adulthood. METHOD: We administered AlloP (10 mg/kg) to rat pups once a day from the 5th to the 9th day after birth. A dose-response study on midazolam in the elevated plus maze test was carried out in adulthood (experiment 1) in order to screen GABAA-benzodiazepine function alterations. Given that the anxiety-like responses were not affected by AlloP, we doubled the initial AlloP dose (experiment 2). One group of pups was left undisturbed with their dams in order to control the effects of daily handling. Only males were behaviorally tested. RESULTS: Neonatal AlloP administration (10 mg/kg) did not alter the behavioral response to midazolam in adulthood at the doses tested. Neonatal AlloP administration at the higher dose (20 mg/kg) induced an anxiolytic-like profile in adulthood (increased entries into and time spent in the open arms), without affecting motor activity. The behavioral effects of neonatal AlloP administration were both selective and independent of daily handling. CONCLUSION: Alterations in AlloP levels during maturation could partly explain the interindividual differences shown by adult subjects in response to environmental stress. PMID- 22094308 TI - A computerized method for automated identification of erect posteroanterior and supine anteroposterior chest radiographs. AB - A computerized scheme was developed for automated identification of erect posteroanterior (PA) and supine anteroposterior (AP) chest radiographs. The method was based on three features, the tilt angle of the scapula superior border, the tilt angle of the clavicle and the extent of radiolucence in lung fields, to identify the view of a chest radiograph. The three indices A(scapula), A(clavicle) and C(lung) were determined from a chest image for the three features. Linear discriminant analysis was used to classify PA and AP chest images based on the three indices. The performance of the method was evaluated by receiver operating characteristic analysis. The proposed method was evaluated using a database of 600 PA and 600 AP chest radiographs. The discriminant performances Az of A(scapula), A(clavicle) and C(lung) were 0.878 +/- 0.010, 0.683 +/- 0.015 and 0.962 +/- 0.006, respectively. The combination of the three indices obtained an Az value of 0.979 +/- 0.004. The results indicate that the combination of the three indices could yield high discriminant performance. The proposed method could provide radiologists with information about the view of chest radiographs for interpretation or could be used as a preprocessing step for analyzing chest images. PMID- 22094309 TI - [The potential of new and old biomarkers for risk stratification in pulmonary embolism]. PMID- 22094310 TI - Antithrombotic therapy in nonvalvular atrial fibrillation: a narrative review. AB - Atrial fibrillation (AF) is an important and potentially modifiable cause of stroke. It has been known since 1989 that oral anticoagulant drugs, such as warfarin, lead to a dramatic decrease in stroke associated with AF. The best risk benefit ratio is obtained with intensity of oral anticoagulant treatment for an INR of 2-3, even in the elderly. Given the risks of anticoagulant therapy, including bleeding, individual thromboembolic risk must be assessed in patients with AF. In 2009, dabigatran was shown to be a reasonable alternative to vitamin K antagonists, establishing itself as a major alternative to warfarin in AF patients. Rivaroxaban and apixaban have subsequently also been shown to be alternatives to warfarin. When there are contraindications to vitamin K antagonists, antiplatelet agents can produce a therapeutic effect, although much less than oral anticoagulants. Apixaban may be a better alternative to aspirin in this setting. Patients with low-risk atrial fibrillation (no risk factors) have not been the subjects of specific clinical trials. It is unclear what would be the best therapeutic choice for these patients. PMID- 22094311 TI - [Sequential double vessel myocardial infarction]. AB - Acute myocardial infarction (AMI) involving acute transmural ischemia of two vascular territories at the same time, which is known as double or combined infarction, is a well described phenomenon but rarely reported in most series of patients admitted for AMI. This may be related to the fact that AMI with multiple vessel obstruction often causes extensive myocardial injury and death before the patient arrives at the hospital. It is speculated that double infarction results from the overall prothrombotic and inflammatory conditions associated with AMI. PMID- 22094312 TI - Determination of the optimal mean arterial pressure for postbleeding resuscitation after hemorrhagic shock in rats. AB - BACKGROUND: The authors previously found that 50-60 mmHg mean arterial blood pressure (MAP) was an optimal target resuscitation pressure for hemorrhagic shock before bleeding was controlled in rats. However, the optimal target resuscitation pressure for hemorrhagic shock after bleeding has been controlled has not been determined. METHODS: A model of uncontrolled hemorrhagic shock was initiated in anesthetized Wistar rats. After 1-h hypotensive resuscitation and bleeding was stopped, rats received fluid resuscitation to different target MAPs (50, 70, or 90 mmHg) with lactated Ringer's solution (LR), 6% hydroxyethyl starch (HES), LR+HES (2:1) or LR+whole blood (2:1) for 2 h. Animal survival, hemodynamic parameters, and vital organ functions were observed. RESULTS: After bleeding had been controlled, mildly hypotensive resuscitation at a target MAP of 70 mmHg increased the survival time and survival rate compared with a target MAP of 50 mmHg and 90 mmHg (P < 0.05 or 0.01). Hemodynamic parameters, cardiac output, oxygen delivery, and vital organ function (including mitochondrial function) in 70 mmHg target MAP groups were better than in other two-target pressure groups (P < 0.05 or 0.01). Among the fluids tested, LR+whole blood (2:1) or LR+HES130 (2:1) had better effects than LR or HES alone at each level of target blood pressure. CONCLUSION: Mildly hypotensive resuscitation is also needed for hemorrhagic shock after bleeding has been controlled, irrespective of whether crystalloids or colloids are used. The optimal target pressure was 70 mmHg in our rat model. A resuscitation pressure that is too low or too high cannot produce a good resuscitative effect. PMID- 22094313 TI - POU1F1-mediated activation of hGH-N by deoxyribonuclease I hypersensitive site II of the human growth hormone locus control region. AB - The human growth hormone gene (hGH-N) is regulated by a distal locus control region (LCR) composed of five deoxyribonuclease I hypersensitive sites (HSs). The region encompassing HSI and HSII contains the predominant pituitary somatotrope specific hGH-N activation function of the LCR. This activity was attributed primarily to POU1F1 (Pit-1) elements at HSI, as linkage to HSI was sufficient for properly regulated hGH-N expression in transgenic mice, while HSII alone had no activity. However, the presence of HSII in conjunction with HSI further enhanced hGH-N transgene expression, indicating additional determinants of pituitary hGH-N activation in the HSII region, but limitations of transgenic models and previous ex vivo systems have prevented the characterization of HSII. In the present study, we employ a novel minichromosome model of the hGH-N regulatory domain and show that HSII confers robust POU1F1-dependent activation of hGH-N in this system. This effect was accompanied by POU1F1-dependent histone acetylation and methylation throughout the minichromosome LCR/hGH-N domain. A series of in vitro DNA binding experiments revealed that POU1F1 binds to multiple sites at HSII, consistent with a direct role in HSII function. Remarkably, POU1F1 binding was localized in part to the 3' untranslated region of a primate-specific LINE-1 (long interspersed nuclear element 1) retrotransposon, suggesting that its insertion during primate evolution may have conferred function to the HSII region in the context of pituitary GH gene regulation. These observations clarify the function of HSII, expanding the role of POU1F1 in hGH LCR activity, and provide insight on the molecular evolution of the LCR. PMID- 22094314 TI - Molecular basis for the activation of a catalytic asparagine residue in a self cleaving bacterial autotransporter. AB - Autotransporters are secreted proteins produced by pathogenic Gram-negative bacteria. They consist of a membrane-embedded beta-domain and an extracellular passenger domain that is sometimes cleaved and released from the cell surface. We solved the structures of three noncleavable mutants of the autotransporter EspP to examine how it promotes asparagine cyclization to cleave its passenger. We found that cyclization is facilitated by multiple factors. The active-site asparagine is sterically constrained to conformations favorable for cyclization, while electrostatic interactions correctly orient the carboxamide group for nucleophilic attack. During molecular dynamics simulations, water molecules were observed to enter the active site and to form hydrogen bonds favorable for increasing the nucleophilicity of the active-site asparagine. When the activated asparagine attacks its main-chain carbonyl carbon, the resulting oxyanion is stabilized by a protonated glutamate. Upon cleavage, this proton could be transferred to the leaving amine group, helping overcome a significant energy barrier. Together, these findings provide insight into factors important for asparagine cyclization, a mechanism broadly used for protein cleavage. PMID- 22094315 TI - Bound for observation. PMID- 22094317 TI - Intravenous rehydration in paediatric gastroenteritis. PMID- 22094318 TI - Violence and poor mental health and functional outcomes. PMID- 22094316 TI - Rapid versus standard intravenous rehydration in paediatric gastroenteritis: pragmatic blinded randomised clinical trial. AB - OBJECTIVE: To determine if rapid rather than standard intravenous rehydration results in improved hydration and clinical outcomes when administered to children with gastroenteritis. DESIGN: Single centre, two arm, parallel randomised pragmatic controlled trial. Blocked randomisation stratified by site. Participants, caregivers, outcome assessors, investigators, and statisticians were blinded to the treatment assignment. SETTING: Paediatric emergency department in a tertiary care centre in Toronto, Canada. PARTICIPANTS: 226 children aged 3 months to 11 years; complete follow-up was obtained on 223 (99%). Eligible children were aged over 90 days, had a diagnosis of dehydration secondary to gastroenteritis, had not responded to oral rehydration, and had been prescribed intravenous rehydration. Children were excluded if they weighed less than 5 kg or more than 33 kg, required fluid restriction, had a suspected surgical condition, or had an insurmountable language barrier. Children were also excluded if they had a history of a chronic systemic disease, abdominal surgery, bilious or bloody vomit, hypotension, or hypoglycaemia or hyperglycaemia. INTERVENTIONS: Rapid (60 mL/kg) or standard (20 mL/kg) rehydration with 0.9% saline over an hour; subsequent fluids administered according to protocol. MAIN OUTCOME MEASURES: PRIMARY OUTCOME: clinical rehydration, assessed with a validated scale, two hours after the start of treatment. SECONDARY OUTCOMES: prolonged treatment, mean clinical dehydration scores over the four hour study period, time to discharge, repeat visits to emergency department, adequate oral intake, and physician's comfort with discharge. Data from all randomised patients were included in an intention to treat analysis. RESULTS: 114 patients were randomised to rapid rehydration and 112 to standard. One child was withdrawn because of severe hyponatraemia at baseline. There was no evidence of a difference between the rapid and standard rehydration groups in the proportions of participants who were rehydrated at two hours (41/114 (36%) v 33/112 (30%); difference 6.5% (95% confidence interval -5.7% to 18.7%; P=0.32). The results did not change after adjustment for weight, baseline dehydration score, and baseline pH (odds ratio 1.8, 0.90 to 3.5; P=0.10). The rates of prolonged treatment were similar (52% rapid v 43% standard; difference 8.9%, 21% to -5%; P=0.19). Although dehydration scores were similar throughout the study period (P=0.96), the median time to discharge was longer in the rapid group (6.3 v 5.0 hours; P=0.03). CONCLUSIONS: There are no relevant clinical benefits from the administration of rapid rather than standard intravenous rehydration to haemodynamically stable children deemed to require intravenous rehydration. Trail registration Clinical Trials NCT00392145. PMID- 22094319 TI - A 41 year old man with an itchy rash. PMID- 22094320 TI - You can stop the bleeding. PMID- 22094321 TI - New education body will tackle variable quality of doctor training. PMID- 22094322 TI - Micro-Raman spectroscopic analysis of the degree of conversion of composite resins containing different initiators cured by polywave or monowave LED units. AB - OBJECTIVES: To determine the degree of conversion (DC) over 48 h post-curing of resin mixtures containing trimethylbenzoyl-diphenylphosphine oxide (TPO) initiator cured by a polywave or a monowave LED light-curing unit (LCU). METHODS: In resin mixtures based on equal weight percent (wt%) of BisGMA and TEGDMA the following initiators were added: 0.2 wt% camphorquinone (CQ)+0.8 wt% ethyl-4 dimethylaminobenzoate (EDMAB) (Group 1); 1 wt% TPO (Group 2) and 0.1 wt% CQ+0.4 wt% EDMAB+0.5 wt% TPO (Group 3). Half of the samples in each group (n=5) were cured using a polywave (bluephase((r)) G2, Ivoclar Vivadent) or a monowave LED LCU (bluephase((r)), Ivoclar Vivadent). The DC was measured using micro-Raman spectroscopy within 5 min and then 1, 3, 6, 24 and 48 h post-irradiation. The data were analysed using general linear model and two-way ANOVA for the factors 'time', 'material', 'surface' and 'LCU' at alpha=0.05. RESULTS: The initial DC values obtained upon light curing remained similar over a 48 h period. bluephase((r)) G2 produced the highest DC in Group 2 followed by Group 3, and Group 1. bluephase((r)) resulted in the highest DC in Group 1, followed by Group 2 and Group 3 (p<0.05). CONCLUSIONS: Unfilled resin materials containing both TPO and CQ-amine initiators are effectively cured using bluephase((r)) G2. Resin mixture with the same wt% of initiators is better cured when TPO is the only initiator, compared to CQ-amine only or combined TPO and CQ-amine system. After initial light cure, no additional conversion of uncured monomers was detected in an unfilled resin material over 48 h at 37 degrees C. PMID- 22094323 TI - From prevention to therapy: minimal intervention with sealants and resin restorative materials. AB - The breakthrough discovery of the acid-etch procedure by Buonocore in the mid 1950s laid the groundwork for the development of pit and fissure sealant as the best preventive agent for use against the development and progression of pit and fissure caries. The acid-etch technique is also the foundational technology behind the ability for clinical dentistry to adapt to a more conservative, minimally invasive, approach to restorative dentistry. The 1970s saw the acid etch technique developed the first foray into minimally invasive operative approaches, which was termed the Preventive Resin Restoration. With the development of the etching of porcelain, additional uses of the acid-etch technique (not discussed here) have led to other conservative procedures such as the porcelain veneer technique and the restorative uses of bonded, etched porcelain, and bonded fixed partial dentures. PMID- 22094324 TI - Diffuse optical imaging and spectroscopy of the breast: a brief outline of history and perspectives. AB - Breast cancer is the most common cancer among women in industrialized countries. At present, X-ray mammography is the gold standard for breast imaging, but has limitations, especially when dense breasts are imaged, as typically occurs in young women. Optical imaging can non-invasively provide information on tissue composition, structure and physiology that can be beneficially exploited for breast lesion detection and identification. In the last few decades optical breast imaging has been investigated, using different geometries (projection imaging and tomography) and measurement techniques (continuous wave, frequency resolved and time resolved approaches). Also, data analysis and display varies significantly, ranging from intensity images to maps of the optical properties (absorption and scattering), tissue composition, and physiological parameters (typically blood volume and oxygenation). This paper outlines the historical evolution of optical imaging and spectroscopy of the breast, highlighting potentialities and limitations, and presents an overview of the main applications and perspectives of the field. PMID- 22094325 TI - Advances in the understanding and management of haematological disorders associated with pregnancy. PMID- 22094326 TI - Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: a synthesis of genetic association studies. AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) is a complex disease with genetic background. The genetic association studies (GAS) that investigated the association between ALL and the MTHFR C677T and A1298C gene variants have produced contradictory or inconclusive results. MATERIALS AND METHODS: In order to decrease the uncertainty of estimated genetic risk effects, a meticulous meta analysis of published GAS related the variants in the MTFHR gene with susceptibility to ALL was conducted. The risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (OR(G)). Cumulative and recursive cumulative meta-analyses were also performed. RESULTS: The analysis showed marginal significant association for the C677T variant, overall [OR=0.91 (0.82-1.00) and OR(G)=0.89 (0.79-1.01)], and in Whites [OR=0.88 (0.77-0.99) and OR(G)=0.85 (0.73-0.99)]. The A1298C variant produced non significant results. For both variants, the cumulative meta-analysis did not show a trend of association as evidence accumulates and the recursive cumulative meta analysis indicated lack of sufficient evidence for denying or claiming an association. CONCLUSION: The current evidence is not sufficient to draw definite conclusions regarding the association of MTHFR variants and development of ALL. PMID- 22094327 TI - The importance of an exponential prostate-specific antigen decline after external beam radiotherapy for intermediate risk prostate cancer. AB - BACKGROUND: To study the influence of an exponential prostate-specific antigen (PSA) decline on biochemical failure after external-beam radiotherapy (EBRT). METHODS: We analyzed 114 patients with intermediate risk prostate cancer (Gleason<=6 and PSA 10-20 or Gleason 7 and PSA <10). Patients were randomized between EBRT doses of either 70.2 Gy or 79.2 Gy (1.8 Gy per day). All patients had a follow up of at least six PSA measurements post-EBRT. Exponential decline and PSA half life were included in a Cox regression analysis for factors associated with biochemical failure. RESULTS: A total of 80/114 (70.2%) patterns were classified as having an exponential PSA decline. Both exponential decline (HR 0.115, 95%CI 0.03-0.44, p=0.0016) and PSA half life ratio were statistically significant predictors (HR 1.03 (95% CI 1.01-1.06)) of biochemical failure. In the model predicting for exponential decline, none of the factors were significant. CONCLUSION: Patients with an exponential PSA decline show a better biochemical outcome in the long term. PMID- 22094328 TI - Near infrared spectroscopy combined with least squares support vector machines and fuzzy rule-building expert system applied to diagnosis of endometrial carcinoma. AB - OBJECTIVE: The feasibility of early diagnosis of endometrial carcinoma was studied by least squares support vector machines (LS-SVM) and fuzzy rule-building expert system (FuRES) that classified near infrared (NIR) spectra of tissues. METHODS: NIR spectra of 77 specimens of endometrium were collected. The spectra were pretreated by principal component orthogonal signal correction (PC-OSC) and direct orthogonal signal correction (DOSC) methods to improve the signal-to-noise ratio (SNR) and remove the influences of background and baseline. The effects of modeling parameters were investigated using bootstrapped Latin-partition methods. RESULTS: The optimal LS-SVM model of the PC-OSC pretreatment method successfully classified the samples with prediction accuracies of 96.8+/-1.4%. CONCLUSIONS: The proposed procedure proved to be rapid and convenient, which is suitable to be developed as a non-invasive diagnosis method for cancer tissue. PMID- 22094330 TI - Posttranslational modifications control FoxO3 activity during denervation. AB - Loss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes, and renal failure, often aggravating pathological progression. The atrophy process is controlled by a transcriptional program that regulates the expression of a subset of genes named atrophy-related genes. The Forkhead Box O (FoxO) family of transcription factors plays a critical role in the atrophy program being sufficient and necessary for the expression of rate limiting enzymes of ubiquitin-proteasome and autophagy-lysosome systems. Therefore, a fine regulation of FoxOs is critical to avoid excessive proteolysis and cachexia. FoxO activity can be modulated by different mechanisms including phosphorylation, acetylation, ubiquitination, and glycosylation. Here we show that FoxO3 is progressively acetylated during denervation and concomitantly atrogin-1, the bona fide FoxO3 target, is downregulated. FoxO3 interacts with the histone acetyl-transferase p300, and its acetylation causes cytosolic relocalization and degradation. Several lysine residues of FoxOs are known to be acetylated. To identify which lysines are critical for FoxO3 activity we have generated different FoxO3 mutants that either mimic or prevent lysine acetylation. We found that FoxO3 mutants that mimic acetylation show a decrease of transcriptional activity and cytosolic localization. Importantly, acetylation induces FoxO3 degradation via proteasome system. Between the different lysines, lysine 262 is critical for translocation of FoxO3. In conclusion, we provide evidence that FoxO3 activity is negatively modulated by acetylation and ubiquitination in a time-dependent and coordinated manner. This fine-tuning mechanism of FoxO3 regulation may be important to prevent excessive muscle loss and can be used as a therapeutic approach to counteract muscle wasting. PMID- 22094329 TI - CDK5 interacts with Slo and affects its surface expression and kinetics through direct phosphorylation. AB - Large-conductance calcium-activated potassium (BK) channels are ubiquitous and play an important role in a number of diseases. In hair cells of the ear, they play a critical role in electrical tuning, a mechanism of frequency discrimination. These channels show variable kinetics and expression along the tonotopic axis. Although the molecular underpinnings to its function in hair cells are poorly understood, it is established that BK channels consist of a pore forming alpha-subunit (Slo) and a number of accessory subunits. Here we identify CDK5, a member of the cyclin-dependent kinase family, as an interacting partner of Slo. We show CDK5 to be present in hair cells and expressed in high concentrations in the cuticular plate and in the circumferential zone. In human embryonic kidney cells, we show that CDK5 inhibits surface expression of Slo by direct phosphorylation of Slo. Similarly, we note that CDK5 affects Slo voltage activation and deactivation kinetics, by a direct phosphorylation of T847. Taken together with its increasing expression along the tonotopic axis, these data suggest that CDK5 likely plays a critical role in electrical tuning and surface expression of Slo in hair cells. PMID- 22094331 TI - H-Ras isoform modulates extracellular matrix synthesis, proliferation, and migration in fibroblasts. AB - Ras GTPases are ubiquitous plasma membrane transducers of extracellular stimuli. In addition to their role as oncogenes, Ras GTPases are key regulators of cell function. Each of the Ras isoforms exhibits specific modulatory activity on different cellular pathways. This has prompted researchers to determine the pathophysiological roles of each isoform. There is a proven relationship between the signaling pathways of transforming growth factor-beta1 (TGF-beta1) and Ras GTPases. To assess the individual role of H-Ras oncogene in basal and TGF-beta1 mediated extracellular matrix (ECM) synthesis, proliferation, and migration in fibroblasts, we analyzed these processes in embryonic fibroblasts obtained from H Ras knockout mice (H-ras(-/-)). We found that H-ras(-/-) fibroblasts exhibited a higher basal phosphatidylinositol-3-kinase (PI3K)/Akt activation than wild-type (WT) fibroblasts, whereas MEK/ERK 1/2 activation was similar in both types of cells. Fibronectin and collagen synthesis were higher in H-ras(-/-) fibroblasts and proliferation was lower in H-ras(-/-) than in WT fibroblasts. Moreover, H-Ras appeared indispensable to maintain normal fibroblast motility, which was highly restricted in H-ras(-/-) cells. These results suggest that H-Ras (through downregulation of PI3K/Akt activation) could modulate fibroblast activity by reducing ECM synthesis and upregulating both proliferation and migration. TGF beta1 strongly increased ERK and Akt activation in WT but not in H-ras(-/-) fibroblasts, suggesting that H-Ras is necessary to increase ERK 1/2 activation and to maintain PI3K downregulation in TGF-beta1-stimulated fibroblasts. TGF beta1 stimulated ECM synthesis and proliferation, although ECM synthesis was higher and proliferation lower in H-ras(-/-) than in WT fibroblasts. Hence, H-Ras activation seems to play a key role in the regulation of these effects. PMID- 22094332 TI - Potential role of insulin signaling on vascular smooth muscle cell migration, proliferation, and inflammation pathways. AB - To investigate the role of insulin signaling pathways in migration, proliferation, and inflammation of vascular smooth muscle cells (VSMCs), we examined the expression of active components of the phosphatidyl inositol 3 (PI 3) kinase (p-Akt) and mitogen-activated protein kinase (MAPK) (p-Erk) in primary cultures of VSMCs from human coronary arteries. VSMCs were treated in a dose response manner with insulin (0, 1, 10, and 100 nM) for 20 min, and Akt and Erk phosphorylation were measured by Western blot analysis. In separate experiments, we evaluated the effect of 200 MUM palmitate, in the presence and absence of 8 MUM pioglitazone, on insulin-stimulated (100 nM for 20 min) Akt and Erk phosphorylation. The phosphorylation of Akt and Erk in VSMCs exhibited a dose dependency with a three- to fourfold increase, respectively, at the highest dose (100 nM). In the presence of palmitate, insulin-induced Akt phosphorylation was completely abolished, and there was a threefold increase in p-Erk. With addition of pioglitazone, the phosphorylation of Akt by insulin remained unchanged, whereas insulin-stimulated Erk phosphorylation was reduced by pioglitazone. These data in VSMCs indicate that high palmitate decreases insulin-stimulated Akt phosphorylation and stimulates MAPK, whereas preexposure peroxisome proliferator activated receptor-gamma agonist pioglitazone preserves Akt phosphorylation and simultaneously attenuates MAPK signaling. Our results suggest that metabolic and mitogenic insulin signals have different sensitivity, are independently regulated, and may play a role in arterial smooth muscle cells migration, proliferation, and inflammation in conditions of acute hyperinsulinemia. PMID- 22094333 TI - A non-cross-bridge, static tension is present in permeabilized skeletal muscle fibers after active force inhibition or actin extraction. AB - When activated muscle fibers are stretched, there is a long-lasting increase in the force. This phenomenon, referred to as "residual force enhancement," has characteristics similar to those of the "static tension," a long-lasting increase in force observed when muscles are stretched in the presence of Ca(2+) but in the absence of myosin-actin interaction. Independent studies have suggested that these two phenomena have a common mechanism and are caused either by 1) a Ca(2+) induced stiffening of titin or by 2) promoting titin binding to actin. In this study, we performed two sets of experiments in which activated fibers (pCa(2+) 4.5) treated with the myosin inhibitor blebbistatin were stretched from 2.7 to 2.8 MUm at a speed of 40 L(o)/s, first, after partial extraction of TnC, which inhibits myosin-actin interactions, or, second, after treatment with gelsolin, which leads to the depletion of thin (actin) filaments. We observed that the static tension, directly related with the residual force enhancement, was not changed after treatments that inhibit myosin-actin interactions or that deplete fibers from troponin C and actin filaments. The results suggest that the residual force enhancement is caused by a stiffening of titin upon muscle activation but not with titin binding to actin. This finding indicates the existence of a Ca(2+) regulated, titin-based stiffness in skeletal muscles. PMID- 22094334 TI - Age-related changes in afferent responses in sensory neurons to mechanical stimulation of osteoblasts in coculture system. AB - Bone homeostasis is regulated by mechanical stimulation (MS). The sensory mechanism of bone tissue for MS remains unknown in the maintenance of bone homeostasis. We aimed to investigate the sensory mechanism from osteoblasts to sensory neurons in a coculture system by MS of osteoblasts. Primary sensory neurons isolated from dorsal root ganglia (DRG) of neonatal, juvenile, and adult mice and osteoblasts isolated from calvaria of neonatal mice were cocultured for 24 h. The responses in DRG neurons elicited by MS of osteoblasts with a glass micropipette were detected by increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) with fluo 3-AM. In all developmental stages mice, [Ca(2+)](i) increasing responses in osteoblasts were promptly elicited by MS. After a short delay, [Ca(2+)](i)-increasing responses were observed in neurites of DRG neurons. The osteoblastic response to second MS was largely attenuated by a stretch activated Ca(2+) channel blocker, gadolinium. The increases of [Ca(2+)](i) in DRG neurons were abolished by a P2 receptor antagonist; suramin, a P2X receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate; and an ATP hydrolyzing enzyme, apyrase. Satellite cells were found around DRG neurons in cocultured cells of only neonatal and juvenile mice. After satellite cells were removed, excessive abnormal responses to MS of osteoblasts were observed in neonatal neurites with unchanged osteoblast responses. The present study indicated that MS of bone tissue elicited afferent P2X receptor-mediated purinergic transmission to sensory neurons in all stages mice. This transmission is modulated by satellite cells, which may have protective actions on sensory neurons. PMID- 22094335 TI - Orai1 and Ca2+-independent phospholipase A2 are required for store-operated Icat SOC current, Ca2+ entry, and proliferation of primary vascular smooth muscle cells. AB - Store-operated Ca(2+) entry (SOCE) is important for multiple functions of vascular smooth muscle cells (SMC), which, depending of their phenotype, can resemble excitable and nonexcitable cells. Similar to nonexcitable cells, Orai1 was found to mediate Ca(2+)-selective (CRAC-like) current and SOCE in dedifferentiated cultured SMC and smooth muscle-derived cell lines. However, the role of Orai1 in cation-selective store-operated channels (cat-SOC), which are responsible for SOCE in primary SMC, remains unclear. Here we focus on primary SMC, and assess the role of Orai1 and Ca(2+)-independent phospholipase A(2) (iPLA(2)beta, or PLA2G6) in activation of cat-SOC current (I(cat-SOC)), SOCE, and SMC proliferation. Using molecular, electrophysiological, imaging, and functional approaches, we demonstrate that molecular knockdown of either Orai1 or iPLA(2)beta leads to similar inhibition of the whole cell cat-SOC current and SOCE in primary aortic SMC and results in significant reduction in DNA synthesis and impairment of SMC proliferation. This is the first demonstration that Orai1 and iPLA(2)beta are equally important for cat-SOC, SOCE, and proliferation of primary aortic SMC. PMID- 22094336 TI - Comparing three basic models for seasonal influenza. AB - In this paper we report the use of the open source Spatiotemporal Epidemiological Modeler (STEM, www.eclipse.org/stem) to compare three basic models for seasonal influenza transmission. The models are designed to test for possible differences between the seasonal transmission of influenza A and B. Model 1 assumes that the seasonality and magnitude of transmission do not vary between influenza A and B. Model 2 assumes that the magnitude of seasonal forcing (i.e., the maximum transmissibility), but not the background transmission or flu season length, differs between influenza A and B. Model 3 assumes that the magnitude of seasonal forcing, the background transmission, and flu season length all differ between strains. The models are all optimized using 10 years of surveillance data from 49 of 50 administrative divisions in Israel. Using a cross-validation technique, we compare the relative accuracy of the models and discuss the potential for prediction. We find that accounting for variation in transmission amplitude increases the predictive ability compared to the base. However, little improvement is obtained by allowing for further variation in the shape of the seasonal forcing function. PMID- 22094337 TI - What types of contacts are important for the spread of infections?: using contact survey data to explore European mixing patterns. AB - Knowledge of the determinants of infectious disease transmission is a public health priority as it allows the design of optimal control strategies for endemic or emerging infections. We analyse a detailed dataset on contact patterns across five European countries and use available serological profiles for varicella and parvovirus B19 infections to identify the types of contact that may be most relevant for transmission. We show that models informed by contact data fit well the observed serological profiles of both infections. We find that intimate types of contacts explain the pattern of acquisition of serological markers by age better than other types of social contacts. We observe similar patterns in each of the countries analysed, suggesting that there are consistent biological mechanisms at work. PMID- 22094338 TI - Incorporating population dynamics into household models of infectious disease transmission. AB - Most household models of disease transmission assume static household distributions. Although this is a reasonable simplification for assessing vaccination strategies at a single point in time or over the course of an outbreak, it has considerable drawbacks for assessing long term vaccination policies or for predicting future changes in immunity. We demonstrate that household models that include births, deaths and movement between households can show dramatically different patterns of infection and immunity to static population models. When immunity is assumed to be life-long, the pattern of births by household size is the key driver of infection, suggesting that the influx of susceptibles has most impact on infection risk in the household. In a comparison of 12 countries, we show that both the crude birth rate and the mean household size affect the risk of infection in households. PMID- 22094339 TI - Evolution of diversity in epidemics revealed by analysis of the human bacterial pathogen group A Streptococcus. AB - Advancements in high-throughput, high-volume data generating techniques increasingly present us with opportunities to probe new areas of biology. In this work we assessed the extent to which four closely related and genetically representative strains of group A Streptococcus causing epidemic disease have differentiated from one another. Comparative genome sequencing, expression microarray analysis, and proteomic studies were used in parallel to assess strain variation. The extent of phenotypic differentiation was unexpectedly large. We found significant associations between genetic polymorphisms and alterations in gene expression allowing us to estimate the frequency with which specific types of polymorphisms alter gene transcription. We identified polymorphisms in the gene (ropB) encoding the RopB regulator that associate with altered transcription of speB and production of the SpeB protein, a critical secreted protease virulence factor. Although these four epidemic strains are closely related, a key discovery is that accumulation of modest genetic changes has rapidly resulted in significant strain phenotypic differentiation, including the extracellular proteome that contains multiple virulence factors. These data provide enhanced understanding of genetic events resulting in strain variation in bacterial epidemics. PMID- 22094340 TI - Modelling management strategies for a disease including undetected sub-clinical infection: bacterial kidney disease in Scottish salmon and trout farms. AB - Disease is a major constraint on animal production and welfare in agriculture and aquaculture. Movement of animals between farms is one of the most significant routes of disease transmission and is particularly hard to control for pathogens with subclinical infection. Renibacterium salmoninarum causes bacterial kidney disease (BKD) in salmonid fish, but infection is often sub-clinical and may go undetected with major potential implications for disease control programmes. A Susceptible-Infected model of R. salmoninarum in Scottish aquaculture has been developed that subdivides the infected phase between known and undetected sub clinically infected farms and diseased farms whose status is assumed to be known. Farms officially known to be infected are subject to movement controls restricting spread of infection. Model results are sensitive to prevalence of undetected infection, which is unknown. However, the modelling suggests that controls that reduce BKD prevalence include improve biosecurity on farms, including those not known to be infected, and improved detection of infection. Culling appears of little value for BKD control. BKD prevalence for rainbow trout farms is less sensitive to controls than it is for Atlantic salmon farms and so different management strategies may be required for the sectors. PMID- 22094341 TI - The decline and resurgence of pertussis in the US. AB - Although the resurgence of pertussis in nations with long-standing vaccination programs has raised serious concerns about the effectiveness of current immunization policy, the epidemiology of resurgence remains poorly understood. We analyzed pertussis notifications in US states obtained from the National Notifiable Disease Surveillance System from 1951 to 2010 to explore the timing, spatial pattern and consistency of resurgence across the country. Here we show that resurgence occurred at different times in different states, spread out over a transition period of roughly three decades. Further, despite this spatial variation, broad patterns in pertussis epidemiology can be described by two dominant phases: (1) a period of decline ending in the mid-1970s, followed by (2) nationwide resurgence. Together, these patterns explain 89.7% of the variation in US case notifications between 1951 and 2005. This resurgence was interrupted, however, by a synchronized downturn in 2005 that continues to the present in many large states. The causes of these two transitions in pertussis epidemiology remain hotly debated, though our findings suggest that evolution of the Bordetella pertussis bacterium, loss of immunity and persistent transmission among adults, and demographic drivers are more probable explanations than changes in reporting or the introduction of acellular vaccines. PMID- 22094342 TI - Sphagnum mosses harbour highly specific bacterial diversity during their whole lifecycle. AB - Knowledge about Sphagnum-associated microbial communities, their structure and their origin is important to understand and maintain climate-relevant Sphagnum dominated bog ecosystems. We studied bacterial communities of two cosmopolitan Sphagnum species, which are well adapted to different abiotic parameters (Sphagnum magellanicum, which are strongly acidic and ombrotrophic, and Sphagnum fallax, which are weakly acidic and mesotrophic), in three Alpine bogs in Austria by a multifaceted approach. Great differences between bacterial fingerprints of both Sphagna were found independently from the site. This remarkable specificity was confirmed by a cloning and a deep sequencing approach. Besides the common Alphaproteobacteria, we found a discriminative spectrum of bacteria; although Gammaproteobacteria dominated S. magellanicum, S. fallax was mainly colonised by Verrucomicrobia and Planctomycetes. Using this information for fluorescent in situ hybridisation analyses, corresponding colonisation patterns for Alphaproteobacteria and Planctomycetes were detected. Bacterial colonies were found in high abundances inside the dead big hyalocytes, but they were always connected with the living chlorocytes. Using multivariate statistical analysis, the abiotic factors nutrient richness and pH were identified to modulate the composition of Sphagnum-specific bacterial communities. Interestingly, we found that the immense bacterial diversity was transferred via the sporophyte to the gametophyte, which can explain the high specificity of Sphagnum-associated bacteria over long distances. In contrast to higher plants, which acquire their bacteria mainly from the environment, mosses as the phylogenetically oldest land plants maintain their bacterial diversity within the whole lifecycle. PMID- 22094343 TI - Resource partitioning in relation to cohabitation of Lactobacillus species in the mouse forestomach. AB - Phylogenetic analysis of gut communities of vertebrates is advanced, but the relationships, especially at the trophic level, between commensals that share gut habitats of monogastric animals have not been investigated to any extent. Lactobacillus reuteri strain 100-23 and Lactobacillus johnsonii strain 100-33 cohabit in the forestomach of mice. According to the niche exclusion principle, this should not be possible because both strains can utilise the two main fermentable carbohydrates present in the stomach digesta: glucose and maltose. We show, based on gene transcription analysis, in vitro physiological assays, and in vivo experiments that the two strains can co-exist in the forestomach habitat because 100-23 grows more rapidly using maltose, whereas 100-33 preferentially utilises glucose. Mutation of the maltose phosphorylase gene (malA) of strain 100 23 prevented its growth on maltose-containing culture medium, and resulted in the numerical dominance of 100-33 in the forestomach. The fundamental niche of L. reuteri 100-23 in the mouse forestomach can be defined in terms of 'glucose and maltose trophism'. However, its realised niche when L. johnsonii 100-33 is present is 'maltose trophism'. Hence, nutritional adaptations provide niche differentiation that assists cohabitation by the two strains through resource partitioning in the mouse forestomach. This real life, trophic phenomenon conforms to a mathematical model based on in vitro bacterial doubling times, in vitro transport rates, and concentrations of maltose and glucose in mouse stomach digesta. PMID- 22094344 TI - The activity level of a microbial community function can be predicted from its metatranscriptome. AB - The objective of this work was to improve our understanding of the quantitative predictive capabilities of metatranscriptomics. To meet this objective, we investigated whether we can predict the activity level of a specific biochemical function based on the abundance of the corresponding gene transcript within measured community metatranscriptomes. In addition, we investigated the lower limit of a microorganism's abundance that still allows detection of its transcripts within a metatranscriptome and prediction of the activity levels of the enzyme encoded by the transcript. To do this, we amended an undefined microbial community with varying fractions of an Escherichia coli strain that can catalyze a specific transformation reaction for the herbicide atrazine. We observed a linear and proportional relationship between the activity level of the transformation reaction and the abundance of its associated encoding transcript down to an E. coli cell density of 0.05% of the population. PMID- 22094346 TI - Anaerobic oxidation of methane at different temperature regimes in Guaymas Basin hydrothermal sediments. AB - Anaerobic oxidation of methane (AOM) was investigated in hydrothermal sediments of Guaymas Basin based on delta(13)C signatures of CH(4), dissolved inorganic carbon and porewater concentration profiles of CH(4) and sulfate. Cool, warm and hot in-situ temperature regimes (15-20 degrees C, 30-35 degrees C and 70-95 degrees C) were selected from hydrothermal locations in Guaymas Basin to compare AOM geochemistry and 16S ribosomal RNA (rRNA), mcrA and dsrAB genes of the microbial communities. 16S rRNA gene clone libraries from the cool and hot AOM cores yielded similar archaeal types such as Miscellaneous Crenarchaeotal Group, Thermoproteales and anaerobic methane-oxidizing archaea (ANME)-1; some of the ANME-1 archaea formed a separate 16S rRNA lineage that at present seems to be limited to Guaymas Basin. Congruent results were obtained by mcrA gene analysis. The warm AOM core, chemically distinct by lower porewater sulfide concentrations, hosted a different archaeal community dominated by the two deep subsurface archaeal lineages Marine Benthic Group D and Marine Benthic Group B, and by members of the Methanosarcinales including ANME-2 archaea. This distinct composition of the methane-cycling archaeal community in the warm AOM core was confirmed by mcrA gene analysis. Functional genes of sulfate-reducing bacteria and archaea, dsrAB, showed more overlap between all cores, regardless of the core temperature. 16S rRNA gene clone libraries with Euryarchaeota-specific primers detected members of the Archaeoglobus clade in the cool and hot cores. A V6-tag high-throughput sequencing survey generally supported the clone library results while providing high-resolution detail on archaeal and bacterial community structure. These results indicate that AOM and the responsible archaeal communities persist over a wide temperature range. PMID- 22094345 TI - Contrasting recombination patterns and demographic histories of the plant pathogen Ralstonia solanacearum inferred from MLSA. AB - We used multilocus sequence analysis (MLSA) on a worldwide collection of the plant pathogenic Ralstonia solanacearum (Betaproteobacteria) to retrace its complex evolutionary history. Using genetic imprints left during R. solanacearum evolution, we were able to delineate distinct evolutionary complex displaying contrasting dynamics. Among the phylotypes already described (I, IIA, IIB, III, IV), eight groups of strains with distinct evolutionary patterns, named clades, were identified. From our recombination analysis, we identified 21 recombination events that occurred within and across these lineages. Although appearing the most divergent and ancestral phylotype, phylotype IV was inferred as a gene donor for the majority of the recombination events that we detected. Whereas this phylotype apparently fuelled the species diversity, ongoing diversification was mainly detected within phylotype I, IIA and III. These three groups presented a recent expanding population structure, a high level of homologous recombination and evidences of long-distance migrations. Factors such as adaptation to a specific host or intense trading of infected crops may have promoted this diversification. Whether R. solanacearum lineages will eventually evolve in distinct species remains an open question. The intensification of cropping and increase of geographical dispersion may favour situations of phylotype sympatry and promote higher exchange of key factors for host adaptation from their common genetic pool. PMID- 22094347 TI - Magnitude and regulation of bacterioplankton respiratory quotient across freshwater environmental gradients. AB - Bacterioplankton respiration (BR) may represent the largest single sink of organic carbon in the biosphere and constitutes an important driver of atmospheric carbon dioxide (CO(2)) emissions from freshwaters. Complete understanding of BR is precluded by the fact that most studies need to assume a respiratory quotient (RQ; mole of CO(2) produced per mole of O(2) consumed) to calculate rates of BR. Many studies have, without clear support, assumed a fixed RQ around 1. Here we present 72 direct measurements of bacterioplankton RQ that we carried out in epilimnetic samples of 52 freshwater sites in Quebec (Canada), using O(2) and CO(2) optic sensors. The RQs tended to converge around 1.2, but showed large variability (s.d.=0.45) and significant correlations with major gradients of ecosystem-level, substrate-level and bacterial community-level characteristics. Experiments with natural bacterioplankton using different single substrates suggested that RQ is intimately linked to the elemental composition of the respired compounds. RQs were on average low in net autotrophic systems, where bacteria likely were utilizing mainly reduced substrates, whereas we found evidence that the dominance of highly oxidized substrates, for example, organic acids formed by photo-chemical processes, led to high RQ in the more heterotrophic systems. Further, we suggest that BR contributes to a substantially larger share of freshwater CO(2) emissions than presently believed based on the assumption that RQ is ~1. Our study demonstrates that bacterioplankton RQ is not only a practical aspect of BR determination, but also a major ecosystem state variable that provides unique information about aquatic ecosystem functioning. PMID- 22094348 TI - Analogous nutrient limitations in unicellular diazotrophs and Prochlorococcus in the South Pacific Ocean. AB - Growth limitation of phytoplankton and unicellular nitrogen (N(2)) fixers (diazotrophs) were investigated in the oligotrophic Western South Pacific Ocean. Based on change in abundances of nifH or 23S rRNA gene copies during nutrient enrichment experiments, the factors limiting net growth of the unicellular diazotrophs UCYN-A (Group A), Crocosphaera watsonii, gamma-Proteobacterium 24774A11, and the non-diazotrophic picocyanobacterium Prochlorococcus, varied within the region. At the westernmost stations, numbers were enhanced by organic carbon added as simple sugars, a combination of iron and an organic chelator, or iron added with phosphate. At stations nearest the equator, the nutrient-limiting growth was not apparent. Maximum net growth rates for UCYN-A, C. watsonii and gamma-24774A11 were 0.19, 0.61 and 0.52 d(-1), respectively, which are the first known empirical growth rates reported for the uncultivated UCYN-A and the gamma 24774A11. The addition of N enhanced total phytoplankton biomass up to 5-fold, and the non-N(2)-fixing Synechococcus was among the groups that responded favorably to N addition. Nitrogen was the major nutrient-limiting phytoplankton biomass in the Western South Pacific Ocean, while availability of organic carbon or iron and organic chelator appear to limit abundances of unicellular diazotrophs. Lack of phytoplankton response to nutrient additions in the Pacific warm pool waters suggests diazotroph growth in this area is controlled by different factors than in the higher latitudes, which may partially explain previously observed variability in community composition in the region. PMID- 22094350 TI - Microbes in thawing permafrost: the unknown variable in the climate change equation. PMID- 22094349 TI - Ecological determinants of the occurrence and dynamics of Vibrio parahaemolyticus in offshore areas. AB - The life cycle of Vibrio parahaemolyticus has been conventionally associated with estuarine areas characterized by moderate salinity and warm seawater temperatures. Recent evidence suggests that the distribution and population dynamics of V. parahaemolyticus may be shaped by the existence of an oceanic transport of communities of this organism mediated by zooplankton. To evaluate this possibility, the presence of V. parahaemolyticus in the water column of offshore areas of Galicia was investigated by PCR monthly over an 18-month period. Analysis of zooplankton and seawater showed that the occurrence of V. parahaemolyticus in offshore areas was almost exclusively associated with zooplankton and was present in 80% of the samples. The influence of environmental factors assessed by generalized additive models revealed that the abundance and seasonality of V. parahaemolyticus in zooplankton was favoured by the concurrence of downwelling periods that promoted the zooplankton patchiness. These results confirm that offshore waters may be common habitats for V. parahaemolyticus, including strains with virulent traits. Additionally, genetically related populations were found in offshore zooplankton and in estuaries dispersed along 1500 km. This finding suggests that zooplankton may operate as a vehicle for oceanic dispersal of V. parahaemolyticus populations, connecting distant regions and habitats, and thereby producing impacts on the local community demography and the spread of Vibrio-related diseases. PMID- 22094351 TI - Phenotyping of tianma-stimulated differentiated rat neuronal b104 cells by quantitative proteomics. AB - Gastrodia elata blume (tianma) is a traditional Chinese herb often used in the treatment of convulsions, headaches, and hypertension. Although interest in neuronal-related actions of tianma is increasing, minimal studies have been conducted to determine its specific effects on neuronal cells. This study was designed to examine the effects of tianma on the metabolism in differentiated neuroblastoma cells using the isobaric tag for relative and absolute quantitation (iTRAQ) technology. Stimulation of these cells with tianma caused changes in the expression of 38 proteins that were subsequently classified according to their physiological functions and association with neurodegenerative diseases. We identified six proteins with altered functional activities in neurodegenerative disease states that were modulated by tianma: triosephosphate isomerase (Tpi1), peptidyl-prolyl cis-trans isomerase A (Ppia), neural cell adhesion molecule 1 (Ncam1), ubiquitin carboxyl-terminal hydrolase isozyme L1 (Uchl1), septin-2 (Sept2) and heat shock protein 90 (Hsp90aa1). We postulate that tianma mediates its neuroprotective effects via upregulation of Ncam1, Hsp90aa1, Tpi1 and Ppia while downregulating Sept2 and Uchl1. These changes in protein expression aid in the restoration of the intracellular environment to a metabolically balanced state, promoting cell survival. Based on these observed data, we conclude that tianma has therapeutic potential, especially for neurodegenerative diseases. PMID- 22094352 TI - Acute tryptophan depletion effects on the vertex and late positive potentials to emotional faces in individuals with a family history of depression. AB - BACKGROUND: Depression, which is associated with dysfunctional serotonin (5-HT) activity, may be characterized by impaired emotional information processing. This study assessed the effects of acute tryptophan depletion (TRP-), which transiently lowers CNS 5-HT, on the emotion-sensitive vertex positive potential (VPP) and late positive potential (LPP) event-related potentials (ERPs) and mood in individuals with a family history of depression. The VPP and LPP are thought to index the early and later stages of motivated attentional processing, respectively. METHOD: Within a double-blind balanced design, ERPs were acquired in 18 individuals with a family history of depression (12 females) after TRP- and TRP+ (balanced) treatment while participants were presented with facial expressions (neutral, as well as sad, joy and surprise at 50 and 100% intensity) and responded to surprised faces. RESULTS: TRP- increased total mood disturbance and maintained depression scores. The VPP and LPP were larger to intense versus mild expressions. Enhanced processing of emotional versus neutral faces, as indexed by the VPP, was primarily evident with TRP-. Speeded and enhanced processing of intensely joyful versus mildly sad faces was found with TRP- (VPP indexed). Compared with TRP+, TRP also increased the VPP to mildly joyful faces. CONCLUSION: Transient 5-HT decreases in individuals with a family history of depression induce subtle changes in early stages of motivated emotional processing, though not in later ones. PMID- 22094353 TI - Atorvastatin and hormone therapy effects on APOE mRNA expression in hypercholesterolemic postmenopausal women. AB - Menopause is associated with changes in lipid levels resulting in increased risk of atherosclerosis and cardiovascular events. Hormone therapy (HT) and atorvastatin have been used to improve lipid profile in postmenopausal women. Effects of HT, atorvastatin and APOE polymorphisms on serum lipids and APOE and LXRA expression were evaluated in 87 hypercholesterolemic postmenopausal women, randomly selected for treatment with atorvastatin (AT, n=17), estrogen or estrogen plus progestagen (HT, n=34) and estrogen or estrogen plus progestagen associated with atorvastatin (HT+AT, n=36). RNA was extracted from peripheral blood mononuclear cells (PBMC) and mRNA expression was measured by TaqMan((r)) PCR. APOE E2/E3/E4 genotyping was performed using PCR-RFLP. Total cholesterol (TC), LDL-c and apoB were reduced after each treatment (p<0.001). Triglycerides, VLDL-c and apoAI were reduced only after atorvastatin (p<0.05), whereas triglycerides and VLDL-c were increased after HT (p=0.01). HT women had lower reduction on TC, LDL-c and apoB than AT and HT+AT groups (p<0.05). APOE mRNA expression was reduced after atorvastatin treatment (p=0.03). Although LXRA gene expression was not modified by atorvastatin, it was correlated with APOE mRNA before and after treatments. Basal APOE mRNA expression was not influenced by gene polymorphisms, however the reduction on APOE expression was more pronounced in E3E3 than in E3E4 carriers. Atorvastatin down-regulates APOE mRNA expression and it is modified by APOE genotypes in PBMC from postmenopausal women. PMID- 22094354 TI - Dasatinib overrides imatinib resistance mediated by the F359I residue mutation in two patients with chronic myeloid leukemia. AB - Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones. PMID- 22094355 TI - Bridging gaps in handoffs: a continuity of care based approach. AB - Handoff among healthcare providers has been recognized as a major source of medical errors. Most prior research has often focused on the communication aspects of handoff, with limited emphasis on the overall handoff process, especially from a clinician workflow perspective. Such a workflow perspective that is based on the continuity of care model provides a framework required to identify and support an interconnected trajectory of care events affecting handoff communication. To this end, we propose a new methodology, referred to as the clinician-centered approach that allows us to investigate and represent the entire clinician workflow prior to, during and, after handoff communication. This representation of clinician activities supports a comprehensive analysis of the interdependencies in the handoff process across the care continuum, as opposed to a single discrete, information sharing activity. The clinician-centered approach is supported by multifaceted methods for data collection such as observations, shadowing of clinicians, audio recording of handoff communication, semi structured interviews and artifact identification and collection. The analysis followed a two-stage mixed inductive-deductive method. The iterative development of clinician-centered approach was realized using a multi-faceted study conducted in the Medical Intensive Care Unit (MICU) of an academic hospital. Using the clinician-centered approach, we (a) identify the nature, inherent characteristics and the interdependencies between three phases of the handoff process and (b) develop a descriptive framework of handoff communication in critical care that captures the non-linear, recursive and interactive nature of collaboration and decision-making. The results reported in this paper serve as a "proof of concept" of our approach, emphasizing the importance of capturing a coordinated and uninterrupted succession of clinician information management and transfer activities in relation to patient care events. PMID- 22094356 TI - Summary of Product Characteristics content extraction for a safe drugs usage. AB - The use of medications has a central role in health care provision, yet on occasion, it may injure the person taking them as result of adverse drug events. A correct drug choice must be modulated to acknowledge both patients' status and drug-specific information. However, this information is locked in free-text and, as such, cannot be actively accessed and elaborated by computerized applications. The goal of this work lies in extracting content (active ingredient, interaction effects, etc.) from the Summary of Product Characteristics, focusing mainly on drug-related interactions, following a machine learning based approach. We compare two state of the art classifiers: conditional random fields with support vector machines. To this end, we introduce a corpus of 100 interaction sections, hand annotated with 13 labels that have been derived from a previously developed conceptual model. The results of our empirical analysis demonstrate that the two models perform well. They exhibit similar overall performance, with an overall accuracy of about 91%. PMID- 22094357 TI - The link between tissue elasticity and thermal dose in vivo. AB - The objective of this study was to investigate in vivo the relationship between stiffness and thermal dose. For this purpose, shear wave elastography (SWE)--a novel ultrasound-based technique for real-time mapping of the stiffness of biological soft tissues--is performed in temperature-controlled experiments. Experiments were conducted on nine anesthetized rats. Their right leg was put in a thermo-regulated waterbath. The right leg of each animal was heated at one particular temperature between 38 degrees C and 48.5 degrees C for 15 min to 3 h. Shear waves were generated in the muscle using the acoustic radiation force induced by a linear ultrasonic probe. The shear wave propagation was imaged in real time by the probe using an ultrafast scanner prototype (10,000 frames s-1). The local tissue stiffness was derived from the shear wave speed. Two optical fiber sensors were inserted into the muscle to measure in situ the temperature. Stiffness was found to increase strongly during the experiments. When expressed as a function of the thermal dose, the stiffness curves were found to be the same for all experiments. A thermal dose threshold was found at 202 min for an eightfold stiffness increase. Finally, the time-temperature relationship was established for different stiffness ratios. The slope of the time-temperature relationship based on stiffness measurements was found identical to the one obtained for cell death in the seminal paper on the thermal dose by Sapareto and Dewey in 1984 (Int. J. Radiat. Oncol. Biol. Phys. 10 787-800). The present results highlight the stiffness increase as a good indicator of thermal necrosis. SWE imaging can be used in vivo for necrosis threshold determination in thermal therapy. PMID- 22094358 TI - Neuroprotective effects of lithium treatment following hypoxic-ischemic brain injury in neonatal rats. AB - PURPOSE: Increasing evidence indicates that lithium is a neuroprotective agent against transient focal and global ischemic injury in the adult animal. In the developing brain, lithium has shown protective effects against neuroapoptosis induced by drugs. This study was designed to investigate the neuroprotective effects of lithium on hypoxic-ischemic brain injury in the neonatal rat. METHODS: Seven-day-old Sprague-Dawley rats underwent hypoxic-ischemic injury (HII) induced by ligation of the common carotid artery followed by exposure to ~2.5 h of hypoxia (~7% oxygen). After HII, rat pups were randomly assigned into two groups: a control group (n = 21), which received a daily subcutaneous injection of 0.9% normal saline for 14 days following HII; and a lithium group (n = 32), treated with daily injection of lithium chloride. N-acetylaspartate/creatinine, choline/creatinine, lipid/creatinine ratios at 1.3 ppm (Lip(1.3)/Cr) and 0.9 ppm (Lip(0.9)/Cr) lipid peaks were evaluated by proton magnetic resonance spectroscopy on the day of HII and on days 7 and 14 after HII. Infarct ratios based on magnetic resonance images were also determined at the same time points. RESULTS: Seven days after HII, the Lip(1.3)/Cr and Lip(0.9)/Cr ratios as well as the infarct ratio were significantly lower in the lithium group than in the control group. The Lip(1.3)/Cr and Lip(0.9)/Cr ratios were significantly correlated with infarct ratio. CONCLUSION: This study showed that post-HII treatment with lithium may have a neuroprotective effect in the immature brain. Further studies are needed to elucidate the mechanism of neuroprotective properties of lithium against HII-induced neonatal brain damage. PMID- 22094360 TI - Case of pituicytoma in childhood. PMID- 22094361 TI - Modeling morphogen gradient formation from arbitrary realistically shaped sources. AB - Much of the analytical modeling of morphogen profiles is based on simplistic scenarios, where the source is abstracted to be point-like and fixed in time, and where only the steady state solution of the morphogen gradient in one dimension is considered. Here we develop a general formalism allowing to model diffusive gradient formation from an arbitrary source. This mathematical framework, based on the Green's function method, applies to various diffusion problems. In this paper, we illustrate our theory with the explicit example of the Bicoid gradient establishment in Drosophila embryos. The gradient formation arises by protein translation from a mRNA distribution followed by morphogen diffusion with linear degradation. We investigate quantitatively the influence of spatial extension and time evolution of the source on the morphogen profile. For different biologically meaningful cases, we obtain explicit analytical expressions for both the steady state and time-dependent 1D problems. We show that extended sources, whether of finite size or normally distributed, give rise to more realistic gradients compared to a single point-source at the origin. Furthermore, the steady state solutions are fully compatible with a decreasing exponential behavior of the profile. We also consider the case of a dynamic source (e.g. bicoid mRNA diffusion) for which a protein profile similar to the ones obtained from static sources can be achieved. PMID- 22094362 TI - A letter to the editor about the article "A model for environmental sex reversal in fish". PMID- 22094364 TI - Model-independent plot of dynamic PET data facilitates data interpretation and model selection. AB - When testing new PET radiotracers or new applications of existing tracers, the blood-tissue exchange and the metabolism need to be examined. However, conventional plots of measured time-activity curves from dynamic PET do not reveal the inherent kinetic information. A novel model-independent volume-influx plot (vi-plot) was developed and validated. The new vi-plot shows the time course of the instantaneous distribution volume and the instantaneous influx rate. The vi-plot visualises physiological information that facilitates model selection and it reveals when a quasi-steady state is reached, which is a prerequisite for the use of the graphical analyses by Logan and Gjedde-Patlak. Both axes of the vi plot have direct physiological interpretation, and the plot shows kinetic parameter in close agreement with estimates obtained by non-linear kinetic modelling. The vi-plot is equally useful for analyses of PET data based on a plasma input function or a reference region input function. The vi-plot is a model-independent and informative plot for data exploration that facilitates the selection of an appropriate method for data analysis. PMID- 22094363 TI - Confinement of gene drive systems to local populations: a comparative analysis. AB - Mosquito-borne diseases such as malaria and dengue fever pose a major health problem through much of the world. One approach to disease prevention involves the use of selfish genetic elements to drive disease-refractory genes into wild mosquito populations. Recently engineered synthetic drive systems have provided encouragement for this strategy; but at the same time have been greeted with caution over the concern that transgenes may spread into countries and communities without their consent. Consequently, there is also interest in gene drive systems that, while strong enough to bring about local population replacement, are unable to establish themselves beyond a partially isolated release site, at least during the testing phase. Here, we develop simple deterministic and stochastic models to compare the confinement properties of a variety of gene drive systems. Our results highlight several systems with desirable features for confinement-a high migration rate required to become established in neighboring populations, and low-frequency persistence in neighboring populations for moderate migration rates. Single-allele underdominance and single-locus engineered underdominance have the strongest confinement properties, but are difficult to engineer and require a high introduction frequency, respectively. Toxin-antidote systems such as Semele, Merea and two-locus engineered underdominance show promising confinement properties and require lower introduction frequencies. Killer-rescue is self limiting in time, but is able to disperse to significant levels in neighboring populations. We discuss the significance of these results in the context of a phased release of transgenic mosquitoes, and the need for characterization of local ecology prior to a release. PMID- 22094365 TI - Outstanding circulation research by Japanese scientists. PMID- 22094366 TI - The developmental history of the gadolinium chelates as intravenous contrast media for magnetic resonance. AB - The developmental history of the gadolinium chelates, which spans 30 years, is described, focusing, in part, on the seminal work with each of the major agents in use today. By examining this history, insight is gained into important issues of efficacy and safety, with valuable lessons to be learned from the mistakes made during this period. An overview of physicochemical characteristics and chemical structures is also provided. The review concludes with a discussion of current research directions involving this field, which is that of the intravenous contrast media for magnetic resonance, in the past 5 years. PMID- 22094367 TI - Variability in core areas of spider monkeys (Ateles geoffroyi) in a tropical dry forest in Costa Rica. AB - Core areas are highly used parts of the home range on which the survival of solitary or group-living animals depends. We investigated the home range and core area size and area fidelity of a spider monkey community in a tropical dry forest over a 4-year period. Home ranges overlapped extensively across years, subgroup sizes, and seasons. In contrast, spider monkeys used core areas that varied in size and location across the study years, subgroup sizes, and seasons. These shifts in core areas suggest that the understanding of core areas, and thus the spatial requirements, of a species in a particular habitat may be limited if based on short-term studies. In this respect, our findings emphasize the importance of long-term studies of the spatial ecology of any species in a particular habitat. Our study also shows that the yearly home range basically includes all the core areas from different years, seasons, and subgroup sizes (i.e., the super-core area). This is conceptually important for territorial species, such as spider monkeys, which defend a stable home range as it contains not only the current, but also the future core areas. PMID- 22094368 TI - Revision of laparoscopic adjustable gastric banding: success or failure? AB - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is a safe and frequently performed bariatric procedure. Unfortunately, re-operations are often necessary. Reports on the success of revisional procedures are scarce and show variable results, either supporting or declining the idea of revising LAGB. This study describes a large cohort of re-operations after failed LAGB to determine the success of revision. METHODS: By use of a prospective cohort, all LAGB revisions performed between 1996 and 2008 were identified. From 301 primary LAGB procedures in our centre, 43 patients (14.3%) required a band revision. In addition, 51 patients were referred from other centres. Our analysis included in total 94 patients with a mean follow-up period of 38 months after revision. RESULTS: Revision was mainly necessary due to anterior slippage (46%) and symmetrical pouch dilatation (36%), which could be resolved by replacing (70%) or refixating the band (27%). Weight loss significantly increased after revision (excess BMI loss (EBMIL), 37.2 +/- 36.3% versus 47.5 +/- 30.4%, P < 0.05). After revision, 23 patients (24%) needed a second re-operation. Patients converted to other procedures (16%) during the second re-operation showed larger weight loss than the revised group (EBMIL, 64.3 +/- 28.1% versus 44.3 +/- 28.7%, P < 0.05). CONCLUSIONS: We report on a large cohort of LAGB revisions with 38 months of follow-up. Revision of failed LAGB by either refixation or replacement of the band is successful and further increases weight loss. PMID- 22094369 TI - Type 2 diabetes mellitus: a possible surgically reversible intestinal dysfunction. AB - Type 2 diabetes mellitus (T2DM) is a global public health problem often associated with obesity. Bariatric surgery is effective for treating serious obesity, and techniques involving intestinal bypass have metabolic benefits, such as complete and early remission of T2DM. We present a literature review of the possible mechanisms of early normalization of glycemic homeostasis after bariatric surgery, including intestinal gluconeogenesis, increased antidiabetogenic signals from L cells located in the distal small intestine, and impaired secretion of diabetogenic signals in the upper part of the small intestine. Adding to these potential mechanisms, unknown factors that regulate insulin sensitivity may be involved and altered by bariatric surgery. This review discusses the various hypotheses about the mechanisms of glycemic control after bariatric surgery involving intestinal bypass. Further research is essential to better understand these mechanisms and to identify potential new mechanisms that might help in developing less invasive and safer alternatives for the treatment of T2DM and reveal novel pharmaceutical targets for glycemic control. PMID- 22094370 TI - Cardiovascular dysautonomia in Parkinson disease: from pathophysiology to pathogenesis. AB - Signs or symptoms of impaired autonomic regulation of circulation often attend Parkinson disease (PD). This review covers biomarkers and mechanisms of autonomic cardiovascular abnormalities in PD and related alpha-synucleinopathies. The clearest clinical laboratory correlate of dysautonomia in PD is loss of myocardial noradrenergic innervation, detected by cardiac sympathetic neuroimaging. About 30-40% of PD patients have orthostatic hypotension (OH), defined as a persistent, consistent fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg within 3 min of change in position from supine to standing. Neuroimaging evidence of cardiac sympathetic denervation is universal in PD with OH (PD+OH). In PD without OH about half the patients have diffuse left ventricular myocardial sympathetic denervation, a substantial minority have partial denervation confined to the inferolateral or apical walls, and a small number have normal innervation. Among patients with partial denervation the neuronal loss invariably progresses over time, and in those with normal innervation at least some loss eventually becomes evident. Thus, cardiac sympathetic denervation in PD occurs independently of the movement disorder. PD+OH also entails extra-cardiac noradrenergic denervation, but this is not as severe as in pure autonomic failure. PD+OH patients have failure of both the parasympathetic and sympathetic components of the arterial baroreflex. OH in PD therefore seems to reflect a "triple whammy" of cardiac and extra-cardiac noradrenergic denervation and baroreflex failure. In contrast, most patients with multiple system atrophy, which can resemble PD+OH clinically, do not have evidence for cardiac or extra-cardiac noradrenergic denervation. Catecholamines in the neuronal cytoplasm are potentially toxic, via spontaneous and enzyme catalyzed oxidation. Normally cytoplasmic catecholamines are efficiently taken up into vesicles via the vesicular monoamine transporter. The recent finding of decreased vesicular uptake in Lewy body diseases therefore suggests a pathogenetic mechanism for loss of catecholaminergic neurons in the periphery and brain. Parkinson disease (PD) is one of the most common chronic neurodegenerative diseases of the elderly, and it is likely that as populations age PD will become even more prevalent and more of a public health burden. Severe depletion of dopaminergic neurons of the nigrostriatal system characterizes and likely produces the movement disorder (rest tremor, slowness of movement, rigid muscle tone, and postural instability) in PD. Over the past two decades, compelling evidence has accrued that PD also involves loss of noradrenergic neurons in the heart. This finding supports the view that loss of catecholaminergic neurons, both in the nigrostriatal system and the heart, is fundamental in PD. By the time PD manifests clinically, most of the nigrostriatal dopaminergic neurons are already lost. Identifying laboratory measures-biomarkers-of the disease process is therefore crucial for advances in treatment and prevention. Deposition of the protein, alpha-synuclein, in the form of Lewy bodies in catecholaminergic neurons is a pathologic hallmark of PD. Alpha-synucleinopathy in autonomic neurons may occur early in the pathogenetic process. The timing of cardiac noradrenergic denervation in PD is therefore a key issue. This review updates the field of autonomic cardiovascular abnormalities in PD and related disorders, with emphasis on relationships among striatal dopamine depletion, sympathetic noradrenergic denervation, and alpha-synucleinopathy. PMID- 22094372 TI - Interlaboratory round robin on cantilever calibration for AFM force spectroscopy. AB - Single-molecule force spectroscopy studies performed by Atomic Force Microscopes (AFMs) strongly rely on accurately determined cantilever spring constants. Hence, to calibrate cantilevers, a reliable calibration protocol is essential. Although the thermal noise method and the direct Sader method are frequently used for cantilever calibration, there is no consensus on the optimal calibration of soft and V-shaped cantilevers, especially those used in force spectroscopy. Therefore, in this study we aimed at establishing a commonly accepted approach to accurately calibrate compliant and V-shaped cantilevers. In a round robin experiment involving eight different laboratories we compared the thermal noise and the Sader method on ten commercial and custom-built AFMs. We found that spring constants of both rectangular and V-shaped cantilevers can accurately be determined with both methods, although the Sader method proved to be superior. Furthermore, we observed that simultaneous application of both methods on an AFM proved an accurate consistency check of the instrument and thus provides optimal and highly reproducible calibration. To illustrate the importance of optimal calibration, we show that for biological force spectroscopy studies, an erroneously calibrated cantilever can significantly affect the derived (bio)physical parameters. Taken together, our findings demonstrated that with the pre-established protocol described reliable spring constants can be obtained for different types of cantilevers. PMID- 22094373 TI - Elemental mapping of multilayered structures: a method to reconstruct 2D chemical maps from a set of 1D line scans. AB - We introduce a method to characterize the chemical distribution in nanostructures using STEM and affiliated spectroscopy techniques. The method is applicable to any nanostructure where the continuous layers of arbitrary geometry and dimensions can be identified. The key feature of the suggested approach is digital warping of the original STEM image into the quasi-1D image. The chemical profiles of high resolution and high signal-to-noise ratio can be extracted from the minimal set of the STEM spectroscopy data while minimizing material damage during acquisitions. Finally, the 2D chemical maps of the area of interest are reconstructed. PMID- 22094374 TI - Grain detection from 2d and 3d EBSD data--specification of the MTEX algorithm. AB - We present a fast and versatile algorithm for the reconstruction of the grain structure from 2d and 3d Electron Back Scatter Diffraction (EBSD) data. The algorithm is rigorously derived from the modeling assumption that grain boundaries are located at the bisectors of adjacent measurement locations. This modeling assumption immediately implies that grains are composed of Voronoi cells corresponding to the measurement locations. Thus our algorithm is based on the Voronoi decomposition of the 2d or 3d measurement domain. It applies to any geometrical configuration of measurement locations and allows for missing data due to measurement errors. The definition of grains as compositions of Voronoi cells implies another fundamental feature of the proposed algorithm--its invariance with respect to spatial displacements, i.e., rotations or shifts of the specimen. This paper also serves as a reference paper for the texture analysis software MTEX, which is a comprehensive and versatile, freely available MATLAB toolbox that covers a wide range of problems in quantitative texture analysis, including the analysis of EBSD data. PMID- 22094375 TI - Pathways of electron transfer photosensitized by thiacyanine dimers. AB - Pathways of electron transfer reaction between p-nitroacetophenone (p-NAP) and ascorbic acid (AA) photosensitized by dimers of 3,3'-disulfopropyl-5,5' dichlorothiacyanine triethylammonium (TC) and 3,3'-disulfopropyl-5,5'-dichloro 9,11-[betabeta-dimethyltrimethylene]thiadicarbocyanine triethylammonium (TDC) are considered. In aqueous solution the dyes are present as an equilibrated mixture of monomers (M(-)) and dimers (M(2)(2-)). In contrast to monomers, the dimers of TC are characterized by a noticeable yield of intersystem crossing, whereas for TDC the triplet-triplet absorption of both monomers and dimers is easily observed upon ns-laser pulse. In the presence of p-NAP and AA the triplet state of the dimers of both dyes is mostly quenched by p-NAP yielding the radical pair [M(2)( )p-NAP(-)] with subsequent dissociation of M(2)(-) into M(-) and M followed by one-electron reduction of M by AA. These steps constitute a pathway of photosensitization by the dimers. For TDC an additional pathway of photosensitization was found to occur. The primary step consists of electron transfer in the excited singlet state of the dimer resulting in the formation of the radicals M and M(2-). The next steps involve one-electron reduction of M by AA and one-electron oxidation of M(2-) by p-NAP which results in the formation of M(-) followed by dimerization. PMID- 22094376 TI - Attack rates of seasonal epidemics. AB - We study the attack rate, that is the total fraction of the population infected each year, for a disease with seasonally varying transmission rate. The attack rate is shown to be governed by both the reproductive number, reflecting the transmissibility of the disease, and the birth rate, which provides a source of new susceptibles. For the case of epidemics which have an annual period (like the seasonality), we prove inequalities which show that the attack rate is close to that of the non-seasonal model, so that it is nearly independent of the strength of the forcing, despite the fact that the shape of the epidemic curve depends strongly on the degree of seasonality of the forcing. Numerical simulations show that this holds to an even stronger extent than is implied by our rigorous results. When the system has subharmonic or chaotic solutions, we show that similar results hold when the attack rate is replaced by the average attack rate over several years. Consequences of these findings for analyzing the effect of vaccination in seasonally-forced models are noted. PMID- 22094377 TI - Functional -1149 g/t polymorphism of the prolactin gene in schizophrenia. AB - BACKGROUND: Prolactin in schizophrenia is considered in the context of antipsychotic drug-induced hyperprolactinemia. However, the European First Episode Schizophrenia Trial showed that hyperprolacti nemia occurred in a significant proportion of drug-naive first-episode schizophrenia patients, which shows that it may also be caused by other factors, including genetic predisposition. Therefore, we investigated the functional polymorphism of the prolactin gene in schizophrenic patients compared with control subjects. METHOD: The experimental group consisted of 403 patients with schizophrenia: 202 females and 201 males. The control group consisted of 653 subjects: 377 females and 276 males. The functional polymorphism -1149 G/T (rs1341239) of the prolactin gene was genotyped using the TaqMan single-nucleotide polymorphism allelic discrimination method. RESULTS: The distribution of genotypes in schizophrenic patients was significantly different from those of the control subjects (p=0.031). After breaking down by gender, for male patients, the difference versus control males was significant for both genotypes and alleles (p=0.031 and p=0.002, respectively), with allele G being observed more frequently in schizophrenic patients. CONCLUSION: The results may suggest a possible abnormality of the functional -1149 G/T polymorphism of the prolactin gene in schizophrenia, especially in male patients, similar to that found in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. This could also correspond with an autoimmune pathogenesis of schizophrenia. PMID- 22094378 TI - High-risk acute promyelocytic leukemia with early differentiation syndrome: a therapeutic dilemma. PMID- 22094379 TI - Bladder perivascular epithelioid cell tumor: a novel rare neoplasm. AB - Perivascular epithelioid cell tumors (PEComas) have recently been defined as a group of neoplasms that have in common the co-expression of melanocytic and smooth muscle markers. We report a novel case of a rare bladder PEComa and we review the relevant literature. PMID- 22094380 TI - Protective effects of urate against 6-OHDA-induced cell injury in PC12 cells through antioxidant action. AB - There is evidence to support that oxidative stress is increased in Parkinson's disease (PD) and contributes to the degeneration of dopaminergic neurons. Recent research has shown that higher blood urate concentrations have now been linked to decreased risks and progression rates of PD. However, the mechanisms about urate to protect dopaminergic neurons are less clear. Our study investigated the effect of urate on oxidative stress induced by 6-hydroxydopamine (6-OHDA) in neuronal differentiated PC12 cells. We found that urate significantly reduced 6-OHDA induced lactate dehydrogenas (LDH), malondialdehyde (MDA), and 8-hydroxy deoxyguanosine (8-OHdG) generation but increased the superoxide dismutase (SOD) activity and glutathione (GSH) levels in the PC12 cells. These results suggested that urate can prevent PC12 cells from oxidative injury induced by 6-OHDA, which may play an important role in the mechanisms underlying the association of high plasma levels of urate with reduced risk and slower progression of PD. Urate treatment could be a potential therapeutic strategy for PD. PMID- 22094381 TI - The trapezius muscle uniquely lacks adaptive process in response to a repeated moderate cognitive stressor. AB - The aim of this study was to examine the adaptive process of muscular responses in healthy subjects over two repeated exposures to the same moderate cognitive stressor. The electromyographic (EMG) activity of the flexor pollicis brevis, biceps brachii, triceps brachii, trapezius, gastrocnemius and soleus muscles was recorded in 35 males during video-recorded Stroop color-word interference tests. The results showed lower EMG activity in all muscles during the second exposure to the stressful task, but not in the trapezius muscle. These findings could help to the understanding of the role of stressful situations in the development of musculoskeletal disorders. PMID- 22094382 TI - Olfactory priming leads to faster sound localization. AB - Cross-modal interactions between vision, audition and touch have been extensively studied in the last decade. However, our understanding of how the chemical senses interact with other sensory modalities remains relatively scarce. We performed a cued auditory localization paradigm in healthy young adults by measuring reaction times to monaural auditory stimuli after subjects had been cued by unilateral olfactory stimuli, mixed olfactory/trigeminal stimuli or somatosensory stimuli. As expected, all cuing conditions led to enhanced performances in auditory localization. Further, both odors led to significantly shorter reaction times when compared to the somatosensory stimuli. We did not observe any effect of side congruency between the cues and the targets. These results suggest facilitative effects of odorous cues independent of a possible trigeminal component in the interaction between olfaction and audition. PMID- 22094383 TI - The effects of the D2 dopamine receptor antagonist, eticlopride, on attention following bilateral vestibular deafferentation in the rat. AB - Loss of vestibular function has been associated with cognitive impairment, including attentional problems. The aim of this study was to investigate the effects of the D(2) dopamine receptor antagonist, eticlopride (0.02, 0.04 and 0.06 mg/kg; s.c.), on attention and impulsivity in rats at 2 months following bilateral vestibular deafferentation (BVD), using a 5 choice serial reaction time task (5CSRTT). The levels of the D(2) receptor protein in the frontal cortex were measured at 1 and 6 months post-BVD using western blotting. Eticlopride caused a dose-dependent decrease in response in the 5CSRTT, which was greater for sham than for BVD rats in terms of the percentage of correct responses and the number of perseverative responses. There were no changes in the amount of the D(2) receptor in the frontal cortex at 1 or 6 months post-BVD; however, D(2) receptor levels were significantly higher on the right side than the left in both sham and BVD animals. These results suggest that BVD causes an increase in perseverative behaviour that D(2) receptor blockade does not eliminate, but that D(2) receptors in the frontal cortex are unchanged. PMID- 22094384 TI - Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to antipsychotic treatment in patients with schizophrenia. AB - The present study is aimed at exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with schizophrenia and whether they could predict clinical outcomes in Korean in patients treated with antipsychotics. One hundred forty five patients with MD, 221 in-patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), were recorded. No significant association was found with the diagnosis of schizophrenia. We observed an association between rs3813296 genotype and improvement on PANSS negative scores. Our findings provide no evidence for an association between SNPs within GRIA1, GRIA2 and GRIA4 under investigation and schizophrenia susceptibility, although rs3813296 (GRIA2) could be associated with improvement on PANSS negative scores. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions. PMID- 22094385 TI - Dizocilpine and cycloheximide prevent inhibition of c-Fos gene expression by delta sleep-inducing peptide in the paraventricular nucleus of the hypothalamus in rats with different resistance to emotional stress. AB - The effects of the non-competitive NMDA-receptor blocker MK-801 (dizocilpine) and the protein synthesis inhibitor cycloheximide on the delta sleep-inducing peptide (DSIP) inhibition of c-Fos immediate early gene expression were studied in the parvocellular subdivision of the hypothalamic paraventricular nucleus (pPVN) of male Wistar rats with either high or low resistance to emotional stress, predicted from differences in their open-field behaviour. The experiments show that intraperitoneal (i.p.) DSIP injection (60 nmol/kg) decreased the number of Fos-immunoreactive (Fos-IR) cells in the pPVN, activated by immobilization. The NMDA-receptor antagonist dizocilpine (MK-801) (90 nmol i.c.v.) prevented the inhibition of c-Fos expression by DSIP in the pPVN of rats predisposed to emotional stress. The protein synthesis inhibitor cycloheximide (210 nmol i.c.v.) prevented the inhibition of c-Fos expression by DSIP in the pPVN of rats that were resistant to emotional stress. The experiments indicate that the DSIP effect on c-Fos gene expression might be mediated by NMDA-receptors. DSIP may induce production of some protein transcription factors, transmitting a signal from membrane NMDA-receptors to the nucleus. PMID- 22094386 TI - Olfactory deficits induce neurofilament hyperphosphorylation. AB - Olfactory dysfunction, including structural abnormalities of the olfactory epithelium, the olfactory bulb and the central olfactory cortices is recognized as an early feature of Alzheimer disease (AD), the most prevalent neurodegenerative disease in aged population characterized by intracellular neurofibrillary tangles (NFTs). How olfactory deficits are linked with AD-like neuropathological changes is still unknown. Here, by using two anosmia animal models, bilateral olfactory bulbectomy (OBX) rats and Cnga2(-/Y) mice, which lack intact olfactory CNG channels, we found the immunoreactivity of phosphorylated neurofilament (NF) are highly increased in the neurites at both the hippocampus and the cortex. As hyperphosphorylated NF is one of the main components of NFTs, our study strongly suggested the underlying correlation of olfactory deficits with AD-like pathological impairments. PMID- 22094387 TI - Rigid cervical collar treatment for geriatric type II odontoid fractures. AB - PURPOSE: To evaluate fracture healing, functional outcomes, complications, and mortality associated with rigid cervical collars. METHODS: Thirty-four patients with <50% odontoid displacement were treated with a rigid cervical collar for 12 weeks (Average age = 84 years). Outcome scores were compared with a group of 40 age-matched control subjects (Average age 79.3). RESULTS: At average 14.9-month follow-up, only 6% demonstrated radiographic evidence of fracture healing and 70% had mobile odontoid nonunion. NDI scores indicated only mild disability, pain scores were low, and neither differed significantly from age-matched controls. Mobile odontoid nonunion was not associated with higher levels of disability or neck pain. Mortality rate was 11.8%. Treatment complications occurred in 6% of patients. CONCLUSIONS: Odontoid nonunion and instability are high in geriatric patients treated with a rigid cervical collar. Fracture healing and stability did not correlate with improved outcomes. Outcomes did not differ significantly from age-matched cohorts. PMID- 22094388 TI - Heritability of scoliosis. AB - PURPOSE: To estimate the heritability of scoliosis in the Swedish Twin Registry. METHODS: Self-reported data on scoliosis from 64,578 twins in the Swedish Twin Registry were analysed. Prevalence, pair- and probandwise concordances and tetrachoric correlations in mono- and dizygotic same-sex twins were calculated. The relative importance of genetic variance, i.e. the heritability, and unique and shared environmental variance was estimated using structural equation modelling in Mx software. In addition, all twins in the twin registry were matched against the Swedish Inpatient Register on the primary diagnosis idiopathic scoliosis. RESULTS: The prevalence of scoliosis was 4%. Pair- and probandwise concordance was 0.11/0.17 for mono- and 0.04/0.08 for same-sex dizygotic twins. The tetrachoric correlation (95% CI) was 0.41 (0.33-0.49) in mono- and 0.18 (0.09-0.29) in dizygotic twins. The most favourable model in the Mx analyses estimated the additive genetic effects (95% CI) to 0.38 (0.18-0.46) and the unique environmental effects to 0.62 (0.54-0.70). Shared environmental effects were not significant. The pairwise/probandwise concordance for idiopathic scoliosis in the Swedish Inpatient Register was 0.08/0.15 for monozygotic and zero/zero for same-sex dizygotic twins. CONCLUSION: Using self-reported data on scoliosis from the Swedish Twin Registry, we estimate that 38% of the variance in the liability to develop scoliosis is due to additive genetic effects and 62% to unique environmental effects. This is the first study of sufficient size to make heritability estimates of scoliosis. PMID- 22094389 TI - Chondromyxoid fibroma of the lumbar spine: case report and literature review. AB - PURPOSE: Chondromyxoid fibroma (CMF) is a benign tumour of the bone that typically occurs in long bone metaphysis. Spinal involvement is uncommon, but more frequent in the cervical and thoracic segments. Lumbar involvement is extremely rare. We report the ninth case of lumbar CMF and the first one involving the articular process of the vertebra. A review of the literature is also intended making special emphasis on the differential diagnosis with other benign spinal tumours of the bone. METHODS: A 21-year-old Caucasian male suffering from low back pain that increased with sports and interrupted sleep was diagnosed with a tumoural lesion in the right inferior articular process of L5. RESULTS: Complete surgical excision of the tumour was accomplished. Histological diagnosis confirmed a CMF. The patient remains asymptomatic at 1-year follow-up. CONCLUSION: Despite the low incidence of CMF in the lumbar spine, differential diagnosis must include this subtype of lesion among other benign tumours of the bone and cartilage. Histological diagnosis is essential in order to provide the patient with an accurate management of the pathology. Recurrence rate is to be considered even in the case of complete surgical excision. Radiotherapy administration is controversial due to suspicion of malignant transformation of the tumour. PMID- 22094391 TI - Novel dual-phase membranes for CO2 capture via an oxyfuel route. AB - Ceria-based dual-phase membranes showing high oxygen permeation fluxes and stability under a CO(2) environment are promising materials for CO(2) capture via an oxyfuel route. The high oxygen permeation fluxes compared with other dual phase membranes are derived from the mixed conducting properties of the perovskite oxides used in the dual-phase membranes. PMID- 22094392 TI - A Monte Carlo model of the Varian IGRT couch top for RapidArc QA. AB - The objectives of this study are to evaluate the effect of couch attenuation on quality assurance (QA) results and to present a couch top model for Monte Carlo (MC) dose calculation for RapidArc treatments. The IGRT couch top is modelled in Eclipse as a thin skin of higher density material with a homogeneous fill of foam of lower density and attenuation. The IGRT couch structure consists of two longitudinal sections referred to as thick and thin. The Hounsfield Unit (HU) characterization of the couch structure was determined using a cylindrical phantom by comparing ion chamber measurements with the dose predicted by the treatment planning system (TPS). The optimal set of HU for the inside of the couch and the surface shell was found to be respectively -960 and -700 HU in agreement with Vanetti et al (2009 Phys. Med. Biol. 54 N157-66). For each plan, the final dose calculation was performed with the thin, thick and without the couch top. Dose differences up to 2.6% were observed with TPS calculated doses not including the couch and up to 3.4% with MC not including the couch and were found to be treatment specific. A MC couch top model was created based on the TPS geometrical model. The carbon fibre couch top skin was modelled using carbon graphite; the density was adjusted until good agreement with experimental data was observed, while the density of the foam inside was kept constant. The accuracy of the couch top model was evaluated by comparison with ion chamber measurements and TPS calculated dose combined with a 3D gamma analysis. Similar to the TPS case, a single graphite density can be used for both the thin and thick MC couch top models. Results showed good agreement with ion chamber measurements (within 1.2%) and with TPS (within 1%). For each plan, over 95% of the points passed the 3D gamma test. PMID- 22094390 TI - Female farmworkers' perceptions of pesticide exposure and pregnancy health. AB - Occupational pesticide exposure may be hazardous to pregnant farmworkers, yet few studies have focused on the health of female farmworkers distinct from their male counterparts or on the impact of agricultural work tasks on pregnancy outcomes. In the current community-based participatory research study, researchers conducted five focus groups with female nursery and fernery workers in Central Florida to enhance knowledge of attitudes about occupational risks and pregnancy health and to gather qualitative data to help form a survey instrument. This article presents the results from questions focused on pesticide exposure and its impact on general, reproductive, pregnancy, and fetal health. Workers reported a belief that pesticide exposure could be hazardous to pregnancy health; descriptions of symptoms and health concerns believed to be related to farmwork and to pesticide exposure; and descriptions of barriers preventing them from practicing safer occupational behaviors. PMID- 22094393 TI - Trans-tragal incision for improved exposure of diacapitular and condylar neck fractures. AB - The authors present a modification of the preauricular approach that improves the exposure of the condyle whilst reducing diacapitular and condylar neck fractures. The incision is a combination of the hockey-stick and endaural incisions. Its inferior part runs within the ear on the posterior face of the tragus; the tragal cartilage is transected together with the retrotragal skin and included in the anterior skin flap. Between May 2009 and December 2010, 16 patients with diacapitular or condylar neck fractures were treated with this approach. All patients showed good occlusion postoperatively and satisfactory aesthetic results. No infection or cartilage necrosis was observed in this series. This approach improves the exposure of the condylar head during the reduction of diacapitular and condylar neck fractures, ensuring easier internal fixation and good cosmetic results. PMID- 22094394 TI - Fronto-facial monobloc distraction in syndromic craniosynostosis. Three dimensional evaluation of treatment outcome and facial growth. AB - The objectives of this study were to investigate the treatment effect and stability of fronto-facial monobloc distraction osteogenesis. Five consecutive patients who underwent monobloc distraction were included (aged 4.8-18.4 years). Three patients had Crouzon syndrome, one had Apert syndrome, and one had Pfeiffer syndrome. The evaluation included clinical records, serial cephalograms for at least 1-year follow up (average 24.6 months). The treatment and post-treatment changes were measured. The intracranial volume, upper airway volume and globe protrusion were calculated from CT before and after treatment. After distraction, the supraorbital region was advanced 15.3mm forward, the midface demonstrated forward advancement of 17.7 mm, 22.1mm and 23.1mm at orbitale, anterior nasal spine and A point, respectively. The downward movement was 2-3mm at maxillary level. The intracranial volume increased 11%; the upper airway volume increased 85% on average. Globe protrusion reduced 3.7 mm on average, which was 20% of underlying skeletal movement. Facial growth demonstrated forward remodelling of the supraorbital region, mild downward but no further forward growth of the midface. Monobloc distraction is effective for relieving related symptoms and signs through differential external distraction at different vertical levels of the face. PMID- 22094395 TI - Fibrillar structures in food. AB - Assembly of proteins or peptides into fibrils is an important subject of study in various research fields. In the field of food research, the protein fibrils are interesting candidates as functional ingredients. It is essential to understand the formation and properties of the fibrils for successful application of the fibrils in food products. This paper describes the impact of recent research on the general view of the process of fibril formation from beta-lg and the properties of the fibrils that are formed, leading to better control of applications for the fibrils. There is a need for a better understanding of the behavior of fibrils in more complex food systems. PMID- 22094396 TI - Most cited articles: ethanol-induced hepatotoxicity, anticarcinogenic effects of polyphenolic compounds in tea, dose-response modeling, novel roles of epoxide hydrolases and arsenic-induced suicidal erythrocyte death. PMID- 22094398 TI - Milestones in melanocytes/melanogenesis. PMID- 22094397 TI - Measurements of transmission spectrums and estimation of retinal blue-light irradiance values of currently available clear and yellow-tinted intraocular lenses. AB - PURPOSE: To compare the spectral transmission characteristics of currently available, foldable, clear and yellow-tinted intraocular lenses (IOLs), and evaluate the protective effects they provide against retinal damage by sunlight. METHODS: We measured the spectral transmittance in the wavelength range of 300 800 nm using a spectrophotometer for 63 IOLs including three clear IOLs (N4-18B, Nidek; X-60, Santen; KS-3Ai, Staar Japan) and four yellow-tinted IOLs (N4-18YG, Nidek; NX-60, Santen; KS-AiN, Staar Japan; NM-1, Hoya) with three different lens powers. The blue-light irradiance (BLI) values through the IOLs were calculated as the retinal hazard index for sungazing. The data from three clear IOLs (SA60AT, Alcon Japan; VA-60BBR, Hoya; AU6K, Kowa) and three yellow-tinted IOLs (SN60AT, Alcon Japan; YA-60BBR, Hoya; AU6N, Kowa) reported previously were also discussed. RESULTS: Except for the X-60, the clear IOLs completely absorbed ultraviolet (UV) light and nearly completely transmitted visible light at wavelengths longer than 440 nm. Yellow-tinted IOLs absorbed more in the blue light range (400-500 nm) than clear IOLs. All IOLs had lower BLI values than aphakic eyes, and all yellow-tinted IOLs had lower BLI values than phakic eyes. The BLI values of the NX-60, KS-AiN, NM-1, SN60AT and YA-60BBR IOLs decreased with the increase in lens power. CONCLUSIONS: Compared to aphakic eyes, currently available UV-blocking clear and yellow-tinted IOLs reduce the BLI values by 43 82%. However, the data presented in this study are not directly applicable to humans implanted with IOLs or for the use of IOLs in a clinical situation, since in those cases the balance between photoprotection and photoreception must be taken into account. PMID- 22094399 TI - The genetics of human pigmentary disorders. PMID- 22094400 TI - Molecular aspects of tanning. PMID- 22094401 TI - The genetics of vitiligo. PMID- 22094402 TI - Key discoveries in melanocyte development. PMID- 22094403 TI - Unpacking human evolution to find the genetic determinants of human skin pigmentation. PMID- 22094404 TI - Determination of melanin synthetic pathways. PMID- 22094406 TI - Differential diagnosis of pulmonary embolism in outpatients with non-specific cardiopulmonary symptoms. AB - Most cardiopulmonary diseases share at least one symptom with pulmonary embolism (PE). The aim of this study was to identify the most common acute causes of dyspnea, chest pain, fainting or palpitations, which diagnostic procedures were performed and whether clinicians investigate them appropriately. An Italian multicenter collaboration gathered 17,497 Emergency Department (ED) records of patients admitted from January 2007 to June 2007 in six hospitals. A block random sampling procedure was applied to select 800 hospitalised patients. Results of the overall 17,497 patients were obtained by weighting sampled cases according to the probability of the randomisation block variables in the whole population. The case-mix of enrolled patients was assessed in terms of cardiopulmonary symptoms, and the prevalence of acute disorders. The actual performance of procedures was compared with a measure of their accuracy as expected in the most common clinical presentations. PE occurred in less than 4% of patients with cardiopulmonary symptoms. Acute heart failure, pneumonia and chronic obstructive pulmonary disease exacerbation were the most likely diagnoses in patients with dyspnea. Acute myocardial infarction was present in roughly 10% of patients with chest pain. Atrial fibrillation was the prevalent diagnosis in patients with palpitations. Echocardiography, computed tomographic pulmonary angiography, perfusion lung scan, D-dimer test and B-type natriuretic peptide were performed less than expected from their accuracy. Diagnostic strategies, starting from non specific symptoms and coping with the eventuality of PE, are likely to benefit from an increased awareness of the examination's accuracy in discriminating among several competing hypotheses, rather than in testing the single PE suspicion. PMID- 22094407 TI - The predictive value of physical examination findings in patients with suspected acute heart failure syndrome. AB - It can be difficult to differentiate acute heart failure syndrome (AHFS) from other causes of acute dyspnea, especially when patients present in extremis. The objective of the study was to determine the predictive value of physical examination findings for pulmonary edema and elevated B-type natriuretic peptide (BNP) levels in patients with suspected AHFS. This was a secondary analysis of a previously reported prospective study of jugular vein ultrasonography in patients with suspected AHFS. Charts were reviewed for physical examination findings, which were then compared to pulmonary edema on chest radiography (CXR) read by radiologists blinded to clinical information and BNP levels measured at presentation. The predictive value of every sign and combination of signs for pulmonary edema on CXR or an elevated BNP was poor. Since physical examination findings alone are not predictive of pulmonary edema or an elevated BNP, clinicians should have a low threshold for using CXR or BNP in clinical evaluation. This brief research report suggests that no physical examination finding or constellation of findings can be used to reliably predict pulmonary edema or an elevated BNP in patients with suspected AHFS. PMID- 22094408 TI - Timing of the initiation of parenteral nutrition in critically ill adults. PMID- 22094409 TI - One in 12 teenagers self harm but most stop spontaneously. PMID- 22094410 TI - Doctors' leaders call for "bold" step to ban smoking in private cars. PMID- 22094411 TI - Production, purification and characterization of mouse monoclonal antibodies against human mitochondrial transcription termination factor 2 (MTERF2). AB - Human mitochondrial transcription termination factor 2 (MTERF2) is a member of the mitochondrial transcription termination factors (MTERFs) family and a cell growth inhibitor. To create a specific mouse monoclonal antibody against human MTERF2, the full-length His-tag MTERF2 protein (1-385 aa) was expressed in Escherichia coli, and purified recombinant protein was injected into three BALB/c mice to perform an immunization procedure. Eight stable positive monoclonal cell lines were screened and established. ELISA results demonstrated that all antibody light chains were kappa, while the heavy chains displayed three subtypes IgG1, IgG2a, and IgG2b respectively. The sensitivity and specificity of the monoclonal antibodies against human MTERF2 were determined using immunoblotting, immunoprecipitation and immunofluorescence analyses. Furthermore, serum regulation of human MTERF2 protein expression levels in human glioma U251 cells was examined with these monoclonal antibodies and the results demonstrated that the expression level of MTERF2 protein was dramatically inhibited by the addition of serum to serum-starved cells. Taken together, our results demonstrate the functionality of these mouse anti-human MTERF2 monoclonal antibodies, which may provide a useful tool to elucidate the role of MTERF2 in human mitochondrial transcription as well as other potential activities. To our knowledge, this is the first report on the preparation and characterization of mouse monoclonal antibodies against human MTERF2. PMID- 22094412 TI - Conference report : The 40th European Muscle Conference, September 14-18, 2011, Berlin, Germany. PMID- 22094413 TI - Overcoming challenges in the study of nitrided microalloyed steels using atom probe. AB - Nitrided steels are widely used in the engineering field due to their superior hardness and other attractive properties. Atom probe tomography (APT) was employed to study two Nb-microalloyed CASTRIP steels with different N contents. A major challenge of using APT to study this group of materials is the presence of tails after Fe peaks in the mass spectra, which overestimates the composition for alloying elements such as Nb and Cu in the steels. One important factor that contributes to the tails is believed to be delayed field evaporation from Fe2+. This artefact of the mass spectrum was observed to be the most severe when voltage pulsing was used. The application of laser pulses with energy ranging from 0.2 to 1.2 nJ successfully reduced the tails and lead to better compositional measurement accuracy. Spatial resolution in the z-direction (along the tip direction) was observed to be less affected by changing laser energy but deteriorates in x-y direction with increasing laser energy. This investigation suggests that pulsed-laser atom probe with ~0.4 nJ laser energy can be used to study this group of materials with improved mass resolution while still maintaining high spatial resolution. PMID- 22094414 TI - ELNES for boron, carbon, and nitrogen K-edges with different chemical environments in layered materials studied by density functional theory. AB - Electron energy-loss near-edge fine structures (ELNES) were calculated for graphene, doped graphene, a hexagonal BN monolayer, and a hexagonal BC2N layer using an ab initio pseudopotential plane wave method including the core-hole effect. Spectral features that can be used to distinguish different chemical environments are identified. The spectral features are closely related to the atomic species and arrangement. The connection between chemical environments and fine structures is discussed. PMID- 22094415 TI - Introduction. AB - Aging in yeast is now a well researched area with hundreds of new research and review papers appearing every year. The chapters following in this book written by some of the leading experts in the field will give an overview of the most relevant areas of yeast aging. The purpose of this chapter is to give the newcomer an introduction to the field including some basic technical questions. PMID- 22094416 TI - Oxidative stresses and ageing. AB - Oxidative damage to cellular constituents has frequently been associated with aging in a wide range of organisms. The power of yeast genetics and biochemistry has provided the opportunity to analyse in some detail how reactive oxygen and nitrogen species arise in cells, how cells respond to the damage that these reactive species cause, and to begin to dissect how these species may be involved in the ageing process. This chapter reviews the major sources of reactive oxygen species that occur in yeast cells, the damage they cause and how cells sense and respond to this damage. PMID- 22094417 TI - The role of mitochondria in the aging processes of yeast. AB - This chapter reviews the role of mitochondria and of mitochondrial metabolism in the aging processes of yeast and the existing evidence for the "mitochondrial theory of aging mitochondrial theory of aging ". Mitochondria are the major source of ATP in the eukaryotic cell but are also a major source of reactive oxygen species reactive oxygen species (ROS) and play an important role in the process of apoptosis and aging. We are discussing the mitochondrial theory of aging mitochondrial theory of aging (TOA), its origin, similarity with other TOAs, and its ramifications which developed in recent decades. The emphasis is on mother cell-specific aging mother cell-specific aging and the RLS (replicative lifespan) with only a short treatment of CLS (chronological lifespan). Both of these aging processes may be relevant to understand also the aging of higher organisms, but they are biochemically very different, as shown by the fact the replicative aging occurs on rich media and is a defect in the replicative capacity of mother cells, while chronological aging occurs in postmitotic cells that are under starvation conditions in stationary phase leading to loss of viability, as discussed elsewhere in this book. In so doing we also give an overview of the similarities and dissimilarities of the various aging processes of the most often used model organisms for aging research with respect to the mitochondrial theory of aging mitochondrial theory of aging. PMID- 22094418 TI - The retrograde response retrograde response and other pathways of interorganelle communication interorganelle communication in yeast replicative aging. AB - A form of mitochondria-to-nucleus signaling mitochondria-to-nucleus signaling is known to play a role in determining replicative life span in yeast. This retrograde response is triggered by experimentally-induced mitochondrial dysfunction mitochondrial dysfunction, but it also is activated during the course of normal replicative aging, allowing yeast to have as long a replicative life span as they do. The components of the retrograde signaling pathway participate in diverse cellular processes such as mitophagy, which appear to be involved in mitochondrial quality control mitochondrial quality control. This plethora of mitochondrial surveillance mitochondrial surveillance mechanisms points to the central importance of this organelle organelle in yeast replicative aging. Additional pathways pathways that monitor mitochondrial status mitochondrial status that do not apparently involve the retrograde response machinery also play a role. A unifying theme is the involvement of the target of rapamycin target of rapamycin (TOR) in both these additional pathways and in the retrograde response. The involvement of TOR brings another large family of signaling events into juxtaposition. Ceramide synthesis is regulated by TOR opening up the potential for coordination of mitochondrial status with a wide array of additional cellular processes. The retrograde response lies at the nexus of metabolic regulation metabolic regulation, stress resistance stress resistance, chromatin-dependent gene regulation chromatin-dependent gene regulation, and genome stability genome stability. In its metabolic outputs, it is related to calorie restriction,calorie restriction, which may be the result of the involvement of TOR. Retrograde response-like processes have been identified in systems other than yeast, including mammalian cells mammalian cells. The retrograde response is a prototypical pathway of interorganelle communication. Other such phenomena are emerging, such as the cross-talk cross-talk between mitochondria mitochondria and the vacuole vacuole, which involves components of the retrograde signaling pathway. The impact of these varied physiological responses on yeast replicative aging remains to be assessed. PMID- 22094420 TI - Aging and the survival of quiescent and non-quiescent cells in yeast stationary phase cultures. AB - In this chapter, we argue that with careful attention to cell types in stationary phase cultures of the yeast, S. cerevisiae provide an excellent model system for aging studies and hold much promise in pinpointing the set of causal genes and mechanisms driving aging. Importantly, a more detailed understanding of aging in this single celled organism will also shed light on aging in tissue-complex model organisms such as C. elegans and D. melanogaster. We feel strongly that the relationship between aging in yeast and tissue-complex organisms has been obscured by failure to notice the heterogeneity of stationary-phase cultures and the processes by which distinct cell types arise in these cultures. Although several studies have used yeast stationary-phase cultures for chronological aging, the majority of these studies have assumed that cultures in stationary phase are homogeneously composed of a single cell type. However, genome-scale analyses of yeast stationary-phase cultures have identified two major cell fractions: quiescent and non-quiescent, which we discuss in detail in this chapter. We review evidence that cell populations isolated from these cultures exhibit population-specific phenotypes spanning a range of metabolic and physiological processes including reproductive capacity, apoptosis, differences in metabolic activities, genetic hyper-mutability, and stress responses. The identification, in S. cerevisiae, of multiple sub-populations having differentiated physiological attributes relevant to aging offers an unprecedented opportunity. This opportunity to deeply understand yeast cellular (and population) aging programs will, also, give insight into genomic and metabolic processes in tissue-complex organism, as well as stem cell biology and the origins of differentiation. PMID- 22094419 TI - Chronological aging in Saccharomyces cerevisiae. AB - The two paradigms to study aging in Saccharomyces cerevisiae are the chronological life span (CLS) and the replicative life span (RLS). The chronological life span is a measure of the mean and maximum survival time of non dividing yeast populations while the replicative life span is based on the mean and maximum number of daughter cells generated by an individual mother cell before cell division stops irreversibly. Here we review the principal discoveries associated with yeast chronological aging and how they are contributing to the understanding of the aging process and of the molecular mechanisms that may lead to healthy aging in mammals. We will focus on the mechanisms of life span regulation by the Tor/Sch9 and the Ras/adenylate Ras/adenylate cyclase/PKA pathways with particular emphasis on those implicating age-dependent oxidative oxidative stress stress and DNA damage/repair. PMID- 22094421 TI - Maximising the yeast chronological lifespan. AB - When investigating aging it is important to focus on the factors that are needed to attain, and which can be manipulated to extend, the longest lifespans. This has long been appreciated by those workers who use Drosophila or Caenorhabditis elegans as model experimental systems to study aging. Often though it seems it is not a consideration in many studies of yeast chronological aging. In this chapter I summarise how recent work has revealed the preconditioning that is needed for yeast to survive for long periods in stationary phase, therefore for it to exhibit a long chronological life span (CLS). Of critical importance in this regard is the nature of the nutrient limitation that, during the earlier growth phase, had forced the cells to undergo growth arrest. I have attempted to highlight those studies that have focussed on the longest CLSs, as this helps to identify investigations that may be addressing - not just factors that can influence chronological longevity - but those factors that are correlated with the authentic processes of chronological aging. Attempting to maximize long-term stationary survival in yeast should also enhance the potential relevance of this organism as an aging model to those who wrestle with the problems of aging in more complex systems. Finally I also give a personal perspective of how studies on the yeast CLS may still yet provide some important new insights into events that are correlated with aging. PMID- 22094423 TI - DNA damage and DNA replication stress in yeast models of aging. AB - DNA damage DNA damage is an important factor in aging in all eukaryotes. Although connections between DNA damage DNA damage and aging have been extensively investigated in complex organisms, only a relatively few studies have investigated DNA damage DNA damage as an aging factor in the model organism S. cerevisiae. Several of these studies point to DNA replication stress DNA replication stress as a cause of age-dependent DNA damage DNA damage in the replicative model of aging, which measures how many times budding yeast cells divide before they senesce and die. Even fewer studies have investigated how DNA damage DNA damage contributes to aging in the chronological aging chronological aging model, which measures how long cells in stationary phase cultures retain reproductive capacity. DNA replication stress DNA replication stress also has been implicated as a factor in chronological aging chronological aging . Since cells in stationary phase are generally considered to be "post-mitotic" and to reside in a quiescent G0/G1 state, the notion that defects in DNA replication might contribute to chronological aging chronological aging appears to be somewhat paradoxical. However, the results of recent studies suggest that a significant fraction of cells in stationary phase cultures are not quiescent, especially in experiments that employ defined medium, which is frequently employed to assess chronological lifespan. Most cells that fail to achieve quiescence remain in a viable, but non-dividing state until they eventually die, similar to the senescent state in mammalian cells. In this chapter we discuss the role of DNA damage DNA damage and DNA replication stress DNA replication stress in both replicative and chronological aging chronological aging in S. cerevisiae. We also discuss the relevance of these findings to the emerging view that DNA damage DNA damage and DNA replication stress DNA replication stress are important components of the senescent state that occurs at early stages of cancer. PMID- 22094424 TI - Yeast aging and apoptosis. AB - A concerted balance between proliferation and apoptosis is essential to the survival of multicellular organisms. Thus, apoptosis per se, although it is a destructive process leading to the death of single cells, also serves as a pro survival mechanism pro-survival mechanism that ensures healthy organismal development and acts as a life-prolonging or anti-aging anti-aging program. The discovery that yeast also possess a functional and, in many cases, highly conserved apoptotic machinery has made it possible to study the relationships between aging and apoptosis in depth using a well-established genetic system and the powerful tools available to yeast researchers for investigating complex physiological and cytological interactions. The aging process of yeast, be it replicative replicative or chronological chronological aging, is closely related to apoptosis, although it remains unclear whether apoptosis is a causal feature of the aging process or vice versa. Nevertheless, experimental results obtained during the past several years clearly demonstrate that yeast serve as a powerful and versatile experimental system for understanding the interconnections between these two fundamentally important cellular and physiological pathways. PMID- 22094422 TI - Amino acid homeostasis and chronological longevity in Saccharomyces cerevisiae. AB - Understanding how non-dividing cells remain viable over long periods of time, which may be decades in humans, is of central importance in understanding mechanisms of aging and longevity. The long-term viability of non-dividing cells, known as chronological longevity, relies on cellular processes that degrade old components and replace them with new ones. Key among these processes is amino acid homeostasis. Amino acid homeostasis requires three principal functions: amino acid uptake, de novo synthesis, and recycling. Autophagy plays a key role in recycling amino acids and other metabolic building blocks, while at the same time removing damaged cellular components such as mitochondria and other organelles. Regulation of amino acid homeostasis and autophagy is accomplished by a complex web of pathways that interact because of the functional overlap at the level of recycling. It is becoming increasingly clear that amino acid homeostasis and autophagy play important roles in chronological longevity in yeast and higher organisms. Our goal in this chapter is to focus on mechanisms and pathways that link amino acid homeostasis, autophagy, and chronological longevity in yeast, and explore their relevance to aging and longevity in higher eukaryotes. PMID- 22094425 TI - Cellular homeostasis in fungi: impact on the aging process. AB - Cellular quality control pathways are needed for maintaining the biological function of organisms. If these pathways become compromised, the results are usually highly detrimental. Functional impairments of cell components can lead to diseases and in extreme cases to organismal death. Dysfunction of cells can be induced by a number of toxic by-products that are formed during metabolic activity, like reactive oxygen and nitrogen species, for example. A key source of reactive oxygen species (ROS) are the organelles of oxidative phosphorylation, mitochondria. Therefore mitochondrial function is also directly affected by ROS, especially if there is a compromised ROS-scavenging capacity. Biological systems therefore depend on several lines of defence to counteract the toxic effects of ROS and other damaging agents. The first level is active at the molecular level and consists of various proteases that bind and degrade abnormally modified and / or aggregated mitochondrial proteins. The second level is concerned with maintaining the quality of whole mitochondria. Among the pathways of this level are mitochondrial dynamics and autophagy (mitophagy). Mitochondrial dynamics describes the time-dependent fusion and fission of mitochondria. It is argued that this kind of organellar dynamics has the power to restore the function of impaired organelles by content mixing with intact organelles. If the first and second lines of defence against damage fail and mitochondria become damaged too severely, there is the option to remove affected cells before they can elicit more damage to their surrounding environment by apoptosis. This form of programmed cell death is strictly regulated by a complex network of interacting components and can be divided into mitochondria-dependent and mitochondria independent modes of action. In this review we give an overview on various biological quality control systems in fungi (yeasts and filamentous fungi) with an emphasis on autophagy (mitophagy) and apoptosis and how these pathways allow fungal organisms to maintain a balanced cellular homeostasis. PMID- 22094426 TI - Genome-wide analysis of yeast aging. AB - In the past several decades the budding yeast Saccharomyces cerevisiae has emerged as a prominent model for aging research. The creation of a single-gene deletion collection covering the majority of open reading frames in the yeast genome and advances in genomic technologies have opened yeast research to genome scale screens for a variety of phenotypes. A number of screens have been performed looking for genes that modify secondary age-associated phenotypes such as stress resistance or growth rate. More recently, moderate-throughput methods for measuring replicative life span and high-throughput methods for measuring chronological life span have allowed for the first unbiased screens aimed at directly identifying genes involved in determining yeast longevity. In this chapter we discuss large-scale life span studies performed in yeast and their implications for research related to the basic biology of aging. PMID- 22094427 TI - Genetic approaches to aging in budding and fission yeasts: new connections and new opportunities. AB - Yeasts are powerful model systems to examine the evolutionarily conserved aspects of eukaryotic aging because they maintain many of the same core cellular signaling pathways and essential organelles as human cells. We constructed a strain of the budding yeast Saccharomyces cerevisiae that could monitor the distribution of proteins involved in heterochromatic silencing and aging, and isolated mutants that alter this distribution. The largest class of such mutants cause defects in mitochondrial function, and appear to cause changes in nuclear silencing separate from the well-known Rtg2p-dependent pathway that alters nuclear transcription in response to the loss of the mitochondrial genome. Mutants that inactivate the ATP2 gene, which encodes the ATPase subunit of the mitochondrial F(1)F(0)-ATPase, were isolated twice in our screen and identify a lifespan extending pathway in a gene that is conserved in both prokaryotes and eukaryotes. The budding yeast S. cerevisiae S. cerevisiae has been used with great success to identify other lifespan-extending pathways in screens using surrogate phenotypes such as stress resistance or silencing to identify random mutants, or in high throughput screens that utilize the deletion strain set resource. However, the direct selection of long-lived mutants from a pool of random mutants is more challenging. We have established a new chronological aging assay for the evolutionarily distant fission yeast Schizosaccharomyces pombe that recapitulates aspects of aging conserved in all eukaryotes. We have constructed a novel S. pombe S. pombe DNA insertion mutant bank, and used it to show that we can directly select for a long-lived mutant. The use of both the budding and fission yeast systems should continue to facilitate the identification and validation of lifespan extending pathways that are conserved in humans. PMID- 22094428 TI - Evolution of asymmetric damage segregation : a modelling approach. AB - Mother cell-specific ageing is a well-known phenomenon in budding yeast Saccharomyces cerevisiae. Asymmetric segregation of damage and its accumulation in the mother cell has been proposed as one important mechanism. There are, however, unicellular organisms such as the fission yeast Schizosaccharomyces pombe, which replicates with almost no asymmetry of segregation of damage and the pathogenic yeast Candida albicans, which falls around the middle of the segregation spectrum far from both complete symmetry and complete asymmetry. The ultimate evolutionary cause that determines the way damage segregates in a given organism is not known. Here we develop a mathematical model to examine the selective forces that drive the evolution of asymmetry and discover the conditions in which symmetry is the optimal strategy. Three main processes are included in the model: protein synthesis (growth), protein damage, and degradation of damage. We consider, for the first time, the costs to the cell that might accompany the evolution of asymmetry and incorporate them into the model along with known trade-offs between reproductive and maintenance investments and their energy requirements. The model provides insight into the relationship between ecology and cellular trade-off physiology in the context of unicellular ageing, and applications of the model may extend to multicellular organisms. PMID- 22094429 TI - Cellular ageing and the actin cytoskeleton. AB - For some time the view that the actin cytoskeleton acts primarily as a scaffold, to be assembled in response to a signaling cascade as an end point in the pathway, has prevailed. However, it is now clear that the dynamic nature of the cytoskeleton is linked to downstream signaling events that further modulate cellular activity, and which can determine cell fate. Examples of this lie within the regulation of programmed cell death, the maintenance of homeostasis and the process of cellular ageing. In yeast the actin cytoskeleton has been shown to interact directly with signaling pathways known to be important in the regulation of both ageing and cell death. For example it has been discovered that the level of damage sustained by the actin cytoskeleton under conditions of oxidative stressoxidative stress is directly linked to apoptosis. Further evidence comes from the finding that actin based propulsion mechanisms are required for the inheritance of mitochondria and anti-ageing factors into newly formed cells. In addition to this actin is known to directly influence the formation of protein aggregations. In this chapter we will discuss these points and postulate as to their significance with respect to the maintenance of cellular homeostasis. PMID- 22094430 TI - Use of interactive telephone technology for longitudinal data collection in a large trial. AB - We report here on the use of interactive telephone technology for collecting longitudinal data in a large randomized non-blinded parallel trial. Data were primarily collected via an automated interactive telephone system which enabled data to be downloaded by researchers periodically via a secure website. Alternative methods were used by some participants to provide data; here we analyze the demographic profiles of groups by preferred data provision, and consider the cost-effectiveness and efficiency of such a system. The automated telephone system was used to provide the majority of data obtained (75.7%), however the group preferring to use this system to provide the majority of their data was on the whole older, more likely to be married, university educated, higher income and white compared to participants preferring to submit their data via personal phone call or post. We conclude that interactive telephone technology provides a means by which large quantities of longitudinal data may be collected efficiently. Depending on the target population, however, considerable staff time may be required to manage attrition and consequent data loss, and alternative strategies should be considered to minimize this. PMID- 22094431 TI - Sample sizes for time-to-event endpoints: should you insure against chance variations in accrual? AB - This note addresses the questions of whether one should safeguard against a potential loss of power due to random variations of the accrual time, how this "insurance" can be formulated, and how much the sample size needs to be increased to obtain it. PMID- 22094433 TI - Interview with Paul Raithby. PMID- 22094432 TI - Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness. AB - BACKGROUND: Stressful life experiences frequently precede the onset of major depression; however, the mechanisms that underlie this link are poorly understood. Importantly, some individuals are more susceptible to the depressogenic effects of stress than others. Carriers of the S or LG allele of the 5-HTTLPR/rs25531 polymorphisms (S' participants) have been found to be more prone to developing depression under stress relative to L or LA homozygotes (L' participants). Moreover, emerging evidence indicates that stress-induced anhedonia may be a mechanism underlying links between stress and depression. Given these findings, we hypothesized that exposure to a naturalistic stressor (school final examinations) would disrupt reward responsiveness (a key behavioral component of anhedonia), and that this effect would be strongest in S' participants. METHODS: To objectively assess reward responsiveness, we administered a probabilistic reward task to 70 Bulgarian high school students over two sessions in the 6-month period preceding school finals. For each participant, the two sessions were designated as the 'stress' and 'control' conditions based on self-reported perceived stress. RESULTS: A genotype*condition interaction emerged in males, with S' participants showing larger stress-related reduction in reward responsiveness relative to L' participants. CONCLUSION: While in need of replication in a larger sample, our results indicate that stress associated with a real-life event is linked to reduced reward responsiveness, the susceptibility to which is modulated by 5-HTTLPR/rs25531 genotype. Although preliminary, these findings identify anhedonia as a promising mechanism linking 5 HTTLPR/rs25531 genotype and stress to depression. PMID- 22094434 TI - Levator-sphincter reinforcement after ultralow anterior resection in patients with low rectal cancer: the surgical method and evaluation of anorectal physiology. AB - PURPOSE: To determine whether ultralow anterior resection with levator-sphincter reinforcement (uLAR-LSR), which is first introduced in the current study, offers functional preservation in patients with low rectal cancer. METHODS: We assessed the functional outcomes in 56 of 61 consecutively enrolled patients who underwent uLAR-LSR. After rectal resection, levator-sphincter reinforcement (LSR) was performed by approximation of the dissected muscles. The functional outcomes were assessed preoperatively, and then 3, 12, and 24 months postoperatively. RESULTS: There were no significant differences in the sphincter or high-pressure zone length between the preoperative and postoperative periods in the uLAR-LSR group (P = 0.298-0.981), which indicated functional preservation by the LSR. The percentage of patients with moderate to severe incontinence (>10 using the Wexner score) was significantly decreased at 24 months as compared to 3 months postoperatively (15.7 vs, 39.6%, P < 0.001). At the limited mean follow-up of 41 months, local recurrence had been detected in one patient (1.8%). CONCLUSION: The uLAR-LSR method is a novel technical option, which maintains the anorectal function as well as accomplishing oncological safety during a short-term evaluation. PMID- 22094435 TI - Systemic inflammatory response syndrome as a predictor of anastomotic leakage after esophagectomy. AB - PURPOSE: Esophageal anastomotic leakage is still a major cause of morbidity and mortality after esophagectomy. We conducted this study to elucidate how anastomotic leakage affects the systemic inflammatory response syndrome (SIRS) criteria. METHODS: The subjects of this retrospective study were 61 patients who underwent esophagectomy. We evaluated their preoperative status, the surgical procedures, and postoperative systemic response, including white blood cell count, heart rate, respiratory rate, body temperature, and laboratory data up to postoperative day (POD) 4. RESULTS: Anastomotic leakage developed in nine patients (14.8%) and was found on POD 7 on average. These patients had a significantly longer hospital stay than those without leakage. Although no difference was observed in postoperative changes of any of the SIRS criteria, the postoperative incidence of SIRS was significantly higher in the patients with anastomotic leakage on POD 4. The number of positive criteria for SIRS was also significantly higher in patients with anastomotic leakage than in those without leakage on PODs 3 and 4. CONCLUSIONS: The SIRS scoring system is valuable for evaluating the severity of systemic inflammatory response caused by anastomosis leakage, and may serve as an indicator for prompt management. PMID- 22094436 TI - Stent strut penetration during thoracic endovascular aortic repair: report of a case. AB - We experienced a serious complication of proximal stent strut penetration (PSSP) during thoracic endovascular aortic repair in a 74-year-old man who underwent two stage hybrid treatment for a distal arch thoracic aortic aneurysm. First, a debranching right common carotid-left common carotid-left subclavian artery bypass was performed. Second, a TALENT Thoracic Stent Graft (Medtronic, Tokyo, Japan) was inserted at Zone 1 (Ishimaru). At deployment, a proximal bare strut accidentally everted and penetrated the aortic wall vertically. Postoperative computed tomography revealed that one crown of the proximal strut had penetrated the aortic wall vertically and had produced an intramural hematoma around the strut. The patient was observed carefully and discharged from the hospital without any sequelae. Seven months after the procedure, there was no remarkable change and his aneurysm was well excluded. PSSP can cause retrograde type-A aortic dissections. A bare strut tends to cause proximal strut penetration more frequently than a covered strut. More caution should be taken in the deployment of a stent graft with a bare strut. PMID- 22094437 TI - A modified liver-hanging maneuver focusing on the ligamentum venosum for left hepatic lobectomy. AB - PURPOSE: The liver-hanging maneuver (LHM) is a useful technique in major hepatectomy. We made modifications to this technique with special reference to the ligamentum venosum for performing a left hepatectomy (LH). The aim of this study was to clarify the usefulness of our new technique. METHODS: Between August 2007 and May 2009, five patients underwent LH using our modified LHM and 12 patients underwent LH using a conventional procedure. The two groups were compared in terms of the patient characteristics, preoperative hepatic functions, surgical records, and outcomes. RESULTS: The characteristics and preoperative hepatic function tests were similar between the modified LHM and non-LHM groups. Intraoperative blood loss was significantly reduced in the modified LHM group compared with the non-LHM group (193 +/- 133 vs. 375 +/- 167 ml, P < 0.05). The lengths of the operations and time required to perform a parenchymal transection did not differ significantly between the two groups (duration of operations 273 +/- 37 vs. 337 +/- 70 min; transection times 29 +/- 10 vs. 28 +/- 13 min). The postoperative complications and hospital stays did not differ significantly between the two groups. CONCLUSION: Our modified LHM can reduce the intraoperative blood loss during LH, and our results have shown the usefulness of this modified technique for LH. PMID- 22094438 TI - Clinical application of an extracellular phosphate-buffered solution (EP-TU) for lung preservation: preliminary results of a Japanese series. AB - PURPOSE: We evaluated the effect of an extracellular phosphate-buffered lung preservation solution (EP-TU solution) on acute postoperative graft function and recipient survival in a Japanese series of cadaveric lung transplantation. METHODS: The subjects were ten patients who received lung grafts preserved with EP-TU solution at three of four designated lung transplant centers between 2000 and 2005. Three of the patients underwent single lung transplantation and seven underwent bilateral lung transplantation. Postoperative graft function was evaluated by primary graft dysfunction (PGD) grade (0-3), arterial oxygen tension/inspired oxygen fraction (PaO(2)/FiO(2)) ratio, and the previously reported chest roentgenogram score (CRS, 0-4) during the first 48 h after intensive care unit admission. Survival rates were also calculated. RESULTS: The average graft ischemic times for the first and second grafts were 431 and 571 min, respectively. The average PGD grade ranged from 0.5 to 1.0 and the average PaO(2)/FiO(2) ratio ranged from 350 to 400 Torr during the 48 h. The average CRS was always under 1.0. Survival rates at 30 days and 5 years were 90 and 80%, respectively. CONCLUSIONS: EP-TU solution promoted excellent postoperative lung graft function and enhanced recipient survival rates, despite a long average preservation time. PMID- 22094439 TI - Different incidence of synchronous liver metastasis between proximal and distal colon cancer. AB - PURPOSE: The clinicopathological features of colon cancer differ between proximal and distal sites; however, the influence of tumor location on liver metastasis has not been fully examined. The aim of this study was to evaluate the differences in the features of liver metastasis between proximal and distal colon cancer. METHODS: The clinicopathological data from 931 colon cancer patients who were treated surgically were examined retrospectively using a multivariate analysis. RESULTS: The incidence of synchronous liver metastasis was 7.1% (31/438) in proximal colon patients and 11.6% (57/493) in distal colon patients. Both univariate and multivariate analyses showed distal colon cancer to be a risk factor for synchronous liver metastasis. CONCLUSION: The incidence of synchronous liver metastasis differs between proximal and distal colon cancer. PMID- 22094440 TI - Inhibitory effects of garcinol and pterostilbene on cell proliferation and adipogenesis in 3T3-L1 cells. AB - The aim of this work was to study the effects of garcinol and pterostilbene on cell proliferation and adipogenesis in 3T3-L1 cells. The results showed that garcinol and pterostilbene decreased the cell population growth and caused cell cycle arrest at the G2/M phase in 3T3-L1 preadipocytes. During adipocyte differentiation, both garcinol and pterostilbene had inhibitory effects on fat droplet formation and triacylglycerol accumulation. The data indicated that garcinol and pterostilbene could inhibit the glycerol-3-phosphate dehydrogenase (GPDH) activity by 97.8 and 61.5%, respectively, as compared to the control. Both garcinol and pterostilbene significantly attenuated the protein expressions of PPARgamma and C/EBPalpha during 3T3-L1 adipocyte differentiation. Moreover, garcinol and pterostilbene caused an inhibition of lipid accumulation in the 3T3 L1 adipocyte differentiation phase. Garcinol and pterostilbene also significantly up-regulated the gene expression of adiponectin as well as down-regulated the gene expressions of leptin, resistin, and fatty acid synthase (FAS) in 3T3-L1 adipocyte differentiation. In 3T3-L1 adipocytes, garcinol significantly down regulated the protein expressions of PPARgamma and FAS as well as up-regulated the protein expressions of adipose triglyceride lipase (ATGL) and adiponectin. Garcinol also significantly up-regulated the gene expression of adiponectin as well as down-regulated the gene expressions of leptin and FAS. These results suggest that garcinol and pterostilbene have anti-adipogenic effects on preadipocytes and adipocytes. PMID- 22094443 TI - Development of hydrophilic photolabile hydroxyl protecting groups. AB - Hydrophilic photolabile protecting groups (PPGs) for hydroxyl protection have been developed. The new PPGs are derived from 3-(dimethylamino)trityl (DMATr) by replacing the two methyl groups with two hydrophilic butyryl groups. The new PPG reagents can be readily prepared and installed. They are stable in the dark but can be removed cleanly and efficiently in aqueous environments upon irradiation with a UV lamp or sunlight. PMID- 22094441 TI - Changes of peroxisome proliferator-activated receptor-gamma on crushed rat sciatic nerves and differentiated primary Schwann cells. AB - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been found to play an essential role in cell proliferation, but whether it was involved in Schwann cells differentiation has never been studied. We have found in sciatic nerve injury that expression of PPAR-gamma decreases mainly in Schwann cells, and it was also increased in differentiated Schwann cells. Further, activated PPAR gamma by the endogenous ligand 15 d-PGJ(2) increased expressions of PPAR-gamma level and Schwann cell differentiation, and this effect may be protected by its antagonist GDW9662. These results indicate that PPAR-gamma could promote Schwann cell differentiation, which plays an important role in peripheral nerve injury and regeneration. PMID- 22094444 TI - A self-reference PRF-shift MR thermometry method utilizing the phase gradient. AB - In magnetic resonance (MR) imaging, the most widely used and accurate method for measuring temperature is based on the shift in proton resonance frequency (PRF). However, inter-scan motion and bulk magnetic field shifts can lead to inaccurate temperature measurements in the PRF-shift MR thermometry method. The self reference PRF-shift MR thermometry method was introduced to overcome such problems by deriving a reference image from the heated or treated image, and approximates the reference phase map with low-order polynomial functions. In this note, a new approach is presented to calculate the baseline phase map in self reference PRF-shift MR thermometry. The proposed method utilizes the phase gradient to remove the phase unwrapping step inherent to other self-reference PRF shift MR thermometry methods. The performance of the proposed method was evaluated using numerical simulations with temperature distributions following a two-dimensional Gaussian function as well as phantom and in vivo experimental data sets. The results from both the numerical simulations and experimental data show that the proposed method is a promising technique for measuring temperature. PMID- 22094446 TI - Seizure probability in animal models of acquired epilepsy: a perspective on the concept of the preictal state. AB - The concept of a preictal state is based on the belief that it may be possible to predict seizures before they occur. The preictal state is viewed as a time period when a seizure is practically inevitable, or at least a period of greatly increased seizure probability. Changes in seizure frequency may provide insight into how seizure probability increases after brain injury. Here, time-dependent changes in the frequency of spontaneous recurrent seizures after brain injury are summarized from published, nearly continuous, electrographic (EEG) recordings of kainate-treated rats and neonatal rats subjected to hypoxia-ischemia. For these animal models, seizure frequency - and thus seizure probability - was a sigmoid function of time after the brain injury. This observation differs from the traditional view, where the development of epilepsy after brain injury is a step function of time, and the latent period is the time between a brain injury and the first spontaneous seizure. Based on backward extrapolation of the plots of seizure frequency versus time, these data suggest that seizure probability increases continuously during the latent period. Also, spontaneous recurrent seizures frequently occurred in clusters, suggesting that the intra-cluster seizure intervals are periods of high seizure probability. Thus, seizure probability progressively increases as a function of time after an epileptogenic brain injury, and is particularly high between seizures within a cluster, as compared to the time between clusters. These data suggest that the detectors of the preictal state need to be accurate (and tested) over a very wide range of seizure probabilities, and that studies on the physiological events that occur during seizure clusters may provide insight on the properties of the preictal state. PMID- 22094445 TI - Multidimensional predictors of fatigue among octogenarians and centenarians. AB - BACKGROUND: Fatigue is a common and frequently observed complaint among older adults. However, knowledge about the nature and correlates of fatigue in old age is very limited. OBJECTIVE: This study examined the relationship of functional indicators, psychological and situational factors and fatigue for 210 octogenarians and centenarians from the Georgia Centenarian Study. METHODS: Three indicators of functional capacity (self-rated health, instrumental activities of daily living, physical activities of daily living), two indicators of psychological well-being (positive and negative affect), two indicators of situational factors (social network and social support), and a multidimensional fatigue scale were used. Blocked multiple regression analyses were computed to examine significant factors related to fatigue. In addition, multi-group analysis in structural equation modeling was used to investigate residential differences (i.e., long-term care facilities vs. private homes) in the relationship between significant factors and fatigue. RESULTS: Blocked multiple regression analyses indicated that two indicators of functional capacity, self-rated health and instrumental activities of daily living, both positive and negative affect, and social support were significant predictors of fatigue among oldest-old adults. The multiple group analysis in structural equation modeling revealed a significant difference among oldest-old adults based on residential status. CONCLUSION: The results suggest that we should not consider fatigue as merely an unpleasant physical symptom, but rather adopt a perspective that different factors such as psychosocial aspects can influence fatigue in advanced later life. PMID- 22094447 TI - Introduction--Epilepsy Research UK Workshop 2010 on "Preictal Phenomena". PMID- 22094448 TI - Living with idiopathic pulmonary fibrosis. PMID- 22094449 TI - Efficacy of diaphragmatic breathing in patients with chronic obstructive pulmonary disease. AB - This study investigated the effects of diaphragmatic breathing (DB) on ventilation and breathing pattern, seeking to identify predictors of its efficacy in patients with chronic obstructive pulmonary disease (COPD). Twenty-nine patients with moderate and severe COPD were monitored using respiratory inductance plethysmography and metabolic gas analysis. After 4 minutes of natural breathing, subjects completed 2 minutes of DB followed by 4 minutes of natural breathing. Dyspnea was measured using a visual analogue scale. Diaphragmatic mobility was assessed using chest radiography. DB was associated with a significant increase in tidal volume and reduction in breathing frequency, leading to higher ventilation and oxygen saturation, with a reduction in dead space ventilation and ventilatory equivalent for carbon dioxide. A total of 10 subjects with moderate (5) and severe (5) COPD performed DB with asynchronous thoracoabdominal motion, worsening the dyspnea, and decreasing the gain of tidal volume. Diaphragmatic mobility, inspiratory muscular strength, lower scores for dyspnea and hypoxemia as well as coordinated thoracoabdominal motion are associated with effective DB. In patients with COPD, DB can improve breathing pattern and ventilatory efficiency without causing dyspnea in patients whose respiratory muscular system is preserved. PMID- 22094450 TI - Developing the model of pulmonary rehabilitation for chronic heart failure. AB - Patients with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) commonly suffer from exertional symptoms of breathlessness and fatigue. The similar systemic manifestations of the conditions, including skeletal muscle dysfunction, are a major contributing factor to the limitation in exercise capacity. A period of exercise training has been shown to improve exercise performance and health-related quality of life for both conditions. Exercise training is a key component of pulmonary rehabilitation (PR) which is now a standard of care for patients with COPD and is symptom based. Although it may be assumed that patients with CHF could be incorporated into cardiac rehabilitation, this is predominantly a secondary prevention programme for patients who are largely asymptomatic. It has been shown that patients with CHF can be successfully trained together with patients with COPD by the same therapists within PR. There are comparable outcome measures that can be used for both COPD and CHF. Many patients with CHF still do not have access to an exercise rehabilitation programme and incorporating them into the PR model of care could be one solution. This article reviews the (1) similar symptoms, mechanisms and consequences between COPD and CHF, (2) rationale and evidence for exercise training in CHF, (3) model of PR, (4) safety of exercise training in CHF, (5) evidence for combined exercise rehabilitation for CHF and COPD, (6) adaptations necessary to include patients with CHF into PR, (7) the chronic care model and (8) summary. PMID- 22094451 TI - Impact of pulmonary vein anatomy assessed by cardiac magnetic resonance imaging on endoscopic pulmonary vein isolation in consecutive patients. AB - AIMS: Recently, the novel endoscopic ablation system (EAS) was introduced and proved its potential for successful pulmonary vein isolation (PVI) in patients suffering from paroxysmal atrial fibrillation (PAF). The current study will investigate the impact of pulmonary vein (PV) anatomy assessed by pre interventional cardiac magnetic resonance imaging (CMRI) on endoscopic PVI. METHODS AND RESULTS: Fifty-one patients (23 females, age 57 +/- 9 years) with a long history (5 +/- 5 years) of drug-refractory PAF were included into our analysis. Cardiac magnetic resonance imaging was performed in all patients before ablation. Each CMRI was evaluated for the number of PVs, for separate or common insertion of ipsilateral PVs, for the PV diameter and PV shape (round vs. oval), for the level of first PV branching, and for the level of insertion of the right inferior PV (RIPV) into the left atrium (LA), respectively. Pulmonary vein isolation was performed using exclusively the novel EAS. The CMRI findings were correlated with the ablation results. A total of 195 PVs were identified and targeted. In 192 of 195 (98%) PVs successful isolation was achieved using the novel EAS irrespective of the PV diameter, the PV shape, the level of PV branching, or the type of insertion of the PV into the LA. There was no statistical significance when correlating the CMRI findings with acute isolation success of the respective PVs or the number of laser applications needed until PVI (P> 0.05). A low level of insertion of the RIPV into the LA was not associated with PVI failure or a higher number of laser applications (P> 0.05). CONCLUSIONS: The majority of PVs could have been targeted and successfully isolated using exclusively the novel EAS irrespective of their anatomy assessed by pre-interventional CMRI. Considering the economical impact of CMRI and its minor influence on ablation strategy, success, and safety it is not an essential pre-requisite for subsequent successful EAS-based PVI. PMID- 22094452 TI - Phrenic nerve stimulation with the quadripolar left ventricular lead not overcome by 'electronic repositioning'. AB - Phrenic nerve stimulation (PNS) is a frequent occurrence in patients implanted with a cardiac resynchronization therapy (CRT) device. The quadripolar left ventricular offers 10 pacing configurations which can overcome PNS in most cases. We report a rare case of significant PNS following upgrade to a CRT which was present with all 10 pacing configurations one day following implantation which required lead repositioning. PMID- 22094453 TI - Risk perception and implantable cardioverter defibrillators. PMID- 22094454 TI - The relation of ventricular arrhythmia electrophysiological characteristics to cardiac phenotype and circadian patterns in hypertrophic cardiomyopathy. AB - BACKGROUND: The triggers of ventricular arrhythmias (VAs) leading to sudden cardiac death in hypertrophic cardiomyopathy (HCM) are ill defined. We sought to examine the electrophysiological characteristics of VAs in HCM and study their relation to cardiac phenotype and circadian patterns using stored intracardiac electrocardiograms from implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: A single centre, observational cohort study of 230 consecutively evaluated ICD recipients with HCM [median age 42 years, 97% primary prevention, 51% with anti-tachycardia pacing (ATP)]. Fifty-six non-clustered VAs (39 initially treated with ATP and 17 with shocks) from 29 patients were analysed. Monomorphic ventricular tachycardia was the culprit arrhythmia in 86% of cases, ventricular fibrillation/flutter in 9%, and polymorphic ventricular tachycardia in 5%. Prior to the onset of VA the rhythm was sinus in 67%, atrial fibrillation/flutter in 19%, and 15% were paced ventricularly; tachycardia (cycle length <600 ms) was present in 25%. Ventricular arrhythmias were triggered by premature ventricular complexes (PVCs) in 72%, which were late-coupled (84%). Short-long-short initiation was seen in 2% and 26% of VAs were sudden-onset without preceding PVCs. Ventricular arrhythmia peaked at midday (with 20% occurring between 2300 and 0700), on Sundays and in May. The cardiac phenotype and time of the day did not predict the mode of initiation. Age at ICD implantation was the only independent predictor of VA cycle length (linear regression coefficient 0.67, 95% CI 0.02-1.32, P= 0.04). Anti-tachycardia pacing terminated 67% of VAs, but patients with ATP therapy had a similar incidence of appropriate shocks (log-rank test P= 0.25) and syncope (log rank P= 0.23) to patients with shock as initial therapy. CONCLUSIONS: Most VAs are monomorphic ventricular tachycardias triggered by late-coupled PVCs. They are frequently terminated by ATP, but ATP does not reduce the frequency of ICD shocks. Younger HCM patients have more rapid VAs, which may explain the peak of sudden cardiac death in early adulthood. The circadian periodicity is different from that observed in ischaemic heart disease, and is likely to relate to the distinct character of the arrhythmogenic substrate in HCM and its modulators. PMID- 22094455 TI - A selective Akt inhibitor produces hypotension and bradycardia in conscious rats due to inhibition of the autonomic nervous system. AB - Akt is a serine-threonine kinase that is amplified in a variety of human cancers, and as with other anticancer agents, some Akt inhibitors have produced functional cardiovascular effects such as marked hypotension that may limit their clinical benefit. Although identified in preclinical studies, the mechanism(s) responsible for these effects are often not fully characterized; potential targets include Akt signaling disruption in cardiac tissue, vascular smooth muscle, and/or autonomic system signaling. A selective Akt inhibitor was found to produce a rapid and marked hypotension and bradycardia in conscious rats. Isolated right atrial tissue and isolated thoracic aortic rings were used to examine direct effects of Akt inhibition on cardiac and vascular tissues, respectively. In addition, rats surgically prepared with telemetry units for monitoring blood pressure and heart rate were used to investigate potential effects on the autonomic nervous system (ANS). Whereas this Akt inhibitor did not produce any significant effect on atrial tissue, it did cause vasorelaxation of aortic rings. More significantly, in conscious rats, the Akt inhibitor inhibited the neural pressor response to the known nicotinic acetylcholine receptor (nAchR) agonist dimethylphenylpiperazinium (DMPP). In fact, the response observed was comparable to the response observed with the known ganglionic blocker hexamethonium. Thus, the hypotension and bradycardia produced by the Akt inhibitor is primarily due to blockade of nAchRs in autonomic ganglia. This finding highlights the importance of evaluating the ANS for cardiovascular effects associated with new chemical entities as well as suggesting a novel direct effect of an Akt inhibitor on nAchRs. PMID- 22094456 TI - Early growth response factor-1 limits biliary fibrosis in a model of xenobiotic induced cholestasis in mice. AB - Hepatic expression of the transcription factor early growth response-1 (Egr-1) is increased in livers of patients with cholestatic liver disease. Bile acid induction of inflammatory genes in hepatocytes is Egr-1 dependent, and Egr-1 expression is increased in livers of mice after bile duct ligation. Of importance, Egr-1 deficiency reduces liver inflammation and injury in that model. However, it is not known whether Egr-1 promotes inflammation in other models of cholestasis. We tested the hypothesis that Egr-1 contributes to liver inflammation in mice exposed chronically to the bile duct epithelial cell (BDEC) toxicant alpha-naphthylisothiocyanate (ANIT). Egr-1-knockout (Egr-1(-/-)) mice and wild-type mice were fed a diet containing 0.025% ANIT for 2 weeks. Expression of Egr-1 mRNA and protein was significantly increased in livers of mice fed ANIT diet. Egr-1 deficiency did not significantly affect ANIT diet-induced hepatocellular injury, inflammatory gene induction, BDEC hyperplasia, or hepatic neutrophil accumulation. In contrast, the deposition of Type 1 collagen was significantly increased in livers of Egr-1(-/-) mice fed ANIT diet compared with wild-type mice fed ANIT diet. Interestingly, this increase in liver fibrosis occurred in association with elevated expression of the beta6 integrin (Itgb6) gene, suggesting the potential for increased local activation of transforming growth factor beta. Taken together, the results indicate that Egr-1 does not contribute to liver injury or inflammation in mice fed a diet containing ANIT. Rather, these studies indicate that Egr-1 deficiency worsens liver fibrosis in conjunction with enhanced expression of the profibrogenic Itgb6 gene. PMID- 22094457 TI - 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) promotes mouse hepatocarcinogenesis by activating transforming growth factor-beta and Wnt/beta-catenin signaling pathways. AB - The purposes of the present study were to investigate the modifying effects of 2 amino-3-methylimidazo[4,5-f]quinoline (IQ), a genotoxic carcinogen produced during cooking of protein-rich foods, and elucidate underlying mechanisms in a two-stage hepatocarcinogenesis mice model. Six-week-old B6C3F1 mice were subjected to two-thirds partial hepatectomy at the beginning of the study, followed by an intraperitoneal injection of diethylnitrosamine on day 1. Starting 1 week later, they were fed diets containing IQ at doses of 30, 100, or 300 ppm for 39 weeks. A dose-dependent trend for increase in eosinophilic altered foci as well as eosinophilic hepatocellular adenomas was observed, along with significant elevation in the incidence of hepatocellular carcinomas in the 100- and 300-ppm IQ groups as compared with initiation control group. Furthermore, IQ elevated the protein expression levels of Wnt1, transforming growth factor-beta (TGF-beta), TGF-beta receptors 1 and 2 (TbetaR1 and TbetaR2), and phosphorylated c-Jun (p-c Jun), while suppressing those of E-cadherin and p21(WAF1/Cip1). Moreover, translocation of beta-catenin to the nuclei as well as upregulated nuclear expression of c-Myc and cyclin D1, which are downstream targets of beta-catenin and p-c-Jun, were detected at 100 and 300 ppm. These findings suggest that IQ exerts dose-dependent promoting effects on mice hepatocarcinogenesis by activating TGF-beta and Wnt/beta-catenin signaling pathways and inhibiting cell adhesion. PMID- 22094458 TI - An NF-kappaB-independent and Erk1/2-dependent mechanism controls CXCL8/IL-8 responses of airway epithelial cells to cadmium. AB - Airway epithelial cells in the lung are the first line of defense against pathogens and environmental pollutants. Inhalation of the environmental pollutant cadmium has been linked to the development of lung cancer and chronic obstructive pulmonary disease, which are diseases characterized by chronic inflammation. To address the role of airway epithelial cells in cadmium-induced lung inflammation, we investigated how cadmium regulates secretion of interleukin 8 (IL-8) by airway epithelial cells. We show that exposure of human airway epithelial cells to subtoxic doses of cadmium in vitro promotes a characteristic inflammatory cytokine response consisting of IL-8, but not IL-1beta or tumor necrosis factor alpha. We also found that intranasal delivery of cadmium increases lung levels of the murine IL-8 homologs macrophage inflammatory protein-2 and keracinocyte derived chemokine and results in an influx of Gr1+ cells into the lung. We determined that inhibition of the nuclear factor-kappaB (NF-kappaB) pathway had no effect on cadmium-induced IL-8 secretion by human airway epithelial cells, suggesting that IL-8 production was mediated through an NF-kappaB-independent pathway. Mitogen-activated protein kinases (MAPKs) are often involved in proinflammatory signaling. Cadmium could activate the main MAPKs (i.e., p38, JNK, and Erk1/2) in human airway epithelial cells. However, only pharmacological inhibition of Erk1/2 pathway or knockdown of the expression of Erk1 and Erk2 using small interfering RNAs suppressed secretion of IL-8 induced by cadmium. Our findings identify cadmium as a potent activator of the proinflammatory cytokine IL-8 in lung epithelial cells and reveal for the first time the role of an NF kappaB-independent but Erk1/2-dependent pathway in cadmium-induced lung inflammation. PMID- 22094459 TI - Subchronic polychlorinated biphenyl (Aroclor 1254) exposure produces oxidative damage and neuronal death of ventral midbrain dopaminergic systems. AB - Recent epidemiologic studies have demonstrated a link between organochlorine and pesticide exposure to an enhanced risk for neurodegenerative disorders such as Parkinson's disease (PD). A common biological phenomenon underlying cell injury associated with both polychlorinated biphenyl (PCB) exposure and dopaminergic neurodegeneration during aging is oxidative stress (OS). In this study, we tested the hypothesis that oral PCB exposure, via food ingestion, impairs dopamine systems in the adult murine brain. We determined whether PCB exposure was associated with OS in dopaminergic neurons, a population of cells that selectively degenerate in PD. After 4 weeks of oral exposure to the PCB mixture Aroclor 1254, several congeners, mostly ortho substituted, accumulated throughout the brain. Significant increases in locomotor activity were observed within 2 weeks, which persisted after cessation of PCB exposure. Stereologic analyses revealed a significant loss of dopaminergic neurons within the substantia nigra and ventral tegmental area. However, striatal dopamine levels were elevated, suggesting that compensatory mechanisms exist to maintain dopamine homeostasis, which could contribute to the observed increases in locomotor activity following PCB exposure. Biochemical experiments revealed alterations in OS markers, including increases in SOD and HO-1 levels and the presence of oxidatively modified lipids and proteins. These findings were accompanied by elevated iron levels within the striatal and midbrain regions, perhaps due to the observed dysregulation of transferrin receptors and ferritin levels following PCB exposure. In this study, we suggest that both OS and the uncoupling of iron regulation contribute to dopamine neuron degeneration and hyperactivity following PCB exposure. PMID- 22094460 TI - The C terminus of formin FMNL3 accelerates actin polymerization and contains a WH2 domain-like sequence that binds both monomers and filament barbed ends. AB - Formin proteins are actin assembly factors that accelerate filament nucleation then remain on the elongating barbed end and modulate filament elongation. The formin homology 2 (FH2) domain is central to these activities, but recent work has suggested that additional sequences enhance FH2 domain function. Here we show that the C-terminal 76 amino acids of the formin FMNL3 have a dramatic effect on the ability of the FH2 domain to accelerate actin assembly. This C-terminal region contains a WASp homology 2 (WH2)-like sequence that binds actin monomers in a manner that is competitive with other WH2 domains and with profilin. In addition, the C terminus binds filament barbed ends. As a monomer, the FMNL3 C terminus inhibits actin polymerization and slows barbed end elongation with moderate affinity. As a dimer, the C terminus accelerates actin polymerization from monomers and displays high affinity inhibition of barbed end elongation. These properties are not common to all formin C termini, as those of mDia1 and INF2 do not behave similarly. Interestingly, mutation of two aliphatic residues, which blocks high affinity actin binding by the WH2-like sequence, has no effect on the ability of the C terminus to enhance FH2-mediated polymerization. However, mutation of three successive basic residues at the C terminus of the WH2-like sequence compromises polymerization enhancement. These results illustrate that the C termini of formins are highly diverse in their interactions with actin. PMID- 22094461 TI - Phospholipase D2 (PLD2) shortens the time required for myeloid leukemic cell differentiation: mechanism of action. AB - Cell differentiation is compromised in acute leukemias. We report that mammalian target of rapamycin (mTOR) and S6 kinase (S6K) are highly expressed in the undifferentiated promyelomonocytic leukemic HL-60 cell line, whereas PLD2 expression is minimal. The expression ratio of PLD2 to mTOR (or to S6K) is gradually inverted upon in vitro induction of differentiation toward the neutrophilic phenotype. We present three ways that profoundly affect the kinetics of differentiation as follows: (i) simultaneous overexpression of mTOR (or S6K), (ii) silencing of mTOR via dsRNA-mediated interference or inhibition with rapamycin, and (iii) PLD2 overexpression. The last two methods shortened the time required for differentiation. By determining how PLD2 participates in cell differentiation, we found that PLD2 interacts with and activates the oncogene Fes/Fps, a protein-tyrosine kinase known to be involved in myeloid cell development. Fes activity is elevated with PLD2 overexpression, phosphatidic acid or phosphatidylinositol bisphosphate. Co-immunoprecipitation indicates a close PLD2-Fes physical interaction that is negated by a Fes-R483K mutant that incapacitates its Src homology 2 domain. All these suggest for the first time the following mechanism: mTOR/S6K down-regulation->PLD2 overexpression->PLD2/Fes association->phosphatidic acid-led activation of Fes kinase->granulocytic differentiation. Differentiation shortening could have a clinical impact on reducing the time of return to normalcy of the white cell counts after chemotherapy in patients with acute promyelocytic leukemia. PMID- 22094462 TI - Negative cross-talk between calcium-sensing receptor and beta-catenin signaling systems in colonic epithelium. AB - Here, we examined the role of the extracellular Ca(2+)-sensing receptor (CaSR) in the control of colonic epithelial cell proliferation in vivo and changes in beta catenin triggered by CaSR stimulation in human colonic epithelial cells in vitro. The in vivo studies, using a novel Casr intestinal-specific knock-out mouse, indicate that the genetic ablation of the Casr leads to hyperproliferation of colonic epithelial cells, expansion of the proliferative zone, changes in crypt structure, and enhanced beta-catenin nuclear localization. The in vitro results indicate that stimulation of the CaSR, by Ca(2+) or by the calcimimetic R-568, produced a striking and time-dependent decrease in the phosphorylation of beta catenin at Ser-552 and Ser-675, two amino acid residues that promote beta-catenin transcriptional activity. The reduced phosphorylation of beta-catenin coincided with a decline in its nuclear localization and a marked redistribution to the plasma membrane. Furthermore, CaSR stimulation promoted a down-regulation of beta catenin-mediated transcriptional activation. These studies demonstrate that signaling pathways emanating from the CaSR control colonic epithelial cell proliferation in vivo and suggest that the mechanism involves regulation of beta catenin phosphorylation. PMID- 22094463 TI - Conserved YjgF protein family deaminates reactive enamine/imine intermediates of pyridoxal 5'-phosphate (PLP)-dependent enzyme reactions. AB - The YjgF/YER057c/UK114 family of proteins is conserved in all domains of life, suggesting that the role of these proteins arose early and was maintained throughout evolution. Metabolic consequences of lacking this protein in Salmonella enterica and other organisms have been described, but the biochemical function of YjgF remained unknown. This work provides the first description of a conserved biochemical activity for the YjgF protein family. Our data support the conclusion that YjgF proteins have enamine/imine deaminase activity and accelerate the release of ammonia from reactive enamine/imine intermediates of the pyridoxal 5'-phosphate-dependent threonine dehydratase (IlvA). Results from structure-guided mutagenesis experiments suggest that YjgF lacks a catalytic residue and that it facilitates ammonia release by positioning a critical water molecule in the active site. YjgF is renamed RidA (reactive intermediate/imine deaminase A) to reflect the conserved activity of the protein family described here. This study, combined with previous physiological studies on yjgF mutants, suggests that intermediates of pyridoxal 5'-phosphate-mediated reactions may have metabolic consequences in vivo that were previously unappreciated. The conservation of the RidA/YjgF family suggests that reactive enamine/imine metabolites are of concern to all organisms. PMID- 22094464 TI - Reduction of glucose uptake through inhibition of hexose transporters and enhancement of their endocytosis by methylglyoxal in Saccharomyces cerevisiae. AB - Diabetes mellitus is characterized by an impairment of glucose uptake even though blood glucose levels are increased. Methylglyoxal is derived from glycolysis and has been implicated in the development of diabetes mellitus, because methylglyoxal levels in blood and tissues are higher in diabetic patients than in healthy individuals. However, it remains to be elucidated whether such factors are a cause, or consequence, of diabetes. Here, we show that methylglyoxal inhibits the activity of mammalian glucose transporters using recombinant Saccharomyces cerevisiae cells genetically lacking all hexose transporters but carrying cDNA for human GLUT1 or rat GLUT4. We found that methylglyoxal inhibits yeast hexose transporters also. Glucose uptake was reduced in a stepwise manner following treatment with methylglyoxal, i.e. a rapid reduction within 5 min, followed by a slow and gradual reduction. The rapid reduction was due to the inhibitory effect of methylglyoxal on hexose transporters, whereas the slow and gradual reduction seemed due to endocytosis, which leads to a decrease in the amount of hexose transporters on the plasma membrane. We found that Rsp5, a HECT type ubiquitin ligase, is responsible for the ubiquitination of hexose transporters. Intriguingly, Plc1 (phospholipase C) negatively regulated the endocytosis of hexose transporters in an Rsp5-dependent manner, although the methylglyoxal-induced endocytosis of hexose transporters occurred irrespective of Plc1. Meanwhile, the internalization of hexose transporters following treatment with methylglyoxal was delayed in a mutant defective in protein kinase C. PMID- 22094465 TI - Functional analysis of DNA replication fork reversal catalyzed by Mycobacterium tuberculosis RuvAB proteins. AB - Initially discovered in Escherichia coli, RuvAB proteins are ubiquitous in bacteria and play a dual role as molecular motor proteins responsible for branch migration of the Holliday junction(s) and reversal of stalled replication forks. Despite mounting genetic evidence for a crucial role of RuvA and RuvB proteins in reversal of stalled replication forks, the mechanistic aspects of this process are still not fully understood. Here, we elucidate the ability of Mycobacterium tuberculosis RuvAB (MtRuvAB) complex to catalyze the reversal of replication forks using a range of DNA replication fork substrates. Our studies show that MtRuvAB, unlike E. coli RuvAB, is able to drive replication fork reversal via the formation of Holliday junction intermediates, suggesting that RuvAB-catalyzed fork reversal involves concerted unwinding and annealing of nascent leading and lagging strands. We also demonstrate the reversal of replication forks carrying hemi-replicated DNA, indicating that MtRuvAB complex-catalyzed fork reversal is independent of symmetry at the fork junction. The fork reversal reaction catalyzed by MtRuvAB is coupled to ATP hydrolysis, is processive, and culminates in the formation of an extended reverse DNA arm. Notably, we found that sequence heterology failed to impede the fork reversal activity of MtRuvAB. We discuss the implications of these results in the context of recognition and processing of varied types of replication fork structures by RuvAB proteins. PMID- 22094466 TI - HAMP domain-mediated signal transduction probed with a mycobacterial adenylyl cyclase as a reporter. AB - HAMP domains, ~55 amino acid motifs first identified in histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis proteins, and phosphatases, operate as signal mediators in two-component signal transduction proteins. A bioinformatics study identified a coevolving signal-accepting network of 10 amino acids in membrane-delimited HAMP proteins. To probe the functionality of this network we used a HAMP containing mycobacterial adenylyl cyclase, Rv3645, as a reporter enzyme in which the membrane anchor was substituted by the Escherichia coli chemotaxis receptor for serine (Tsr receptor) and the HAMP domain alternately with that from the protein Af1503 of the archaeon Archaeoglobus fulgidus or the Tsr receptor. In a construct with the Tsr-HAMP, cyclase activity was inhibited by serine, whereas in a construct with the HAMP domain from A. fulgidus, enzyme activity was not responsive to serine. Amino acids of the signal accepting network were mutually swapped between both HAMP domains, and serine signaling was examined. The data biochemically tentatively established the functionality of the signal-accepting network. Based on a two-state gearbox model of rotation in HAMP domain-mediated signal propagation, we characterized the interaction between permanent and transient core residues in a coiled coil HAMP structure. The data are compatible with HAMP rotation in signal propagation but do not exclude alternative models for HAMP signaling. Finally, we present data indicating that the connector, which links the alpha-helices of HAMP domains, plays an important structural role in HAMP function. PMID- 22094467 TI - Chondroitin sulfate "wobble motifs" modulate maintenance and differentiation of neural stem cells and their progeny. AB - Chondroitin sulfate/dermatan sulfate (CS/DS) proteoglycans, major components of the central nervous system, have the potential to interact with a wide range of growth factors and neurotrophic factors that influence neuronal migration, axon guidance pathways, and neurite outgrowth. Recent studies have also revealed the role of CS/DS chains in the orchestration of the neural stem/progenitor cell micromilieu. Individual functional proteins recognize a set of multiple overlapping oligosaccharide sequences decorated to give different sulfation patterns, which are termed here "wobble CS/DS oligosaccharide motifs," and induce signaling pathways essential for the proliferation, self-renewal, and cell lineage commitment of neural stem/progenitor cells. PMID- 22094468 TI - Activation of Aurora-A kinase by protein partner binding and phosphorylation are independent and synergistic. AB - Protein kinases are activated by phosphorylation and by the binding of activator proteins. The interplay of these two factors is incompletely understood. We applied energetic analysis to this question and characterized the activation process of the serine/threonine kinase Aurora-A by phosphorylation and by its protein partner, targeting protein for Xenopus kinesin-like protein 2 (TPX2). We discovered that these two activators act synergistically and without a predefined order: each can individually increase the activity of Aurora-A, and the effect of both bound together is the exact sum of their individual contributions to catalysis. Unexpectedly, the unphosphorylated enzyme has catalytic activity that is increased 15-fold by the binding of TPX2 alone. The energetic contribution of phosphorylation to catalysis is 2-fold greater than that of TPX2 binding, which is independent of the phosphorylation state of the enzyme. Based on this analysis, we propose a revised, fluid model of Aurora-A activation in which the first step is a reduction in the mobility of the activation loop by either TPX2 binding or phosphorylation. Furthermore, our results suggest that unphosphorylated Aurora-A bound to the mitotic spindle by TPX2 is catalytically active and that the phosphorylation state of Aurora-A is an inaccurate surrogate for its activity. Extending this form of analysis will allow us to compare quantitatively the effects of the whole network of kinase-activating partners. Comparison with other kinases showed that kinetic characterization detects those kinases whose activation loops undergo a rearrangement upon phosphorylation and thus whose unphosphorylated state offers a distinct target for the development of Type II inhibitors. PMID- 22094469 TI - Acute activation of central GLP-1 receptors enhances hepatic insulin action and insulin secretion in high-fat-fed, insulin resistant mice. AB - Glucagon-like peptide-1 (GLP-1) receptor knockout (Glp1r(-/-)) mice exhibit impaired hepatic insulin action. High fat (HF)-fed Glp1r(-/-) mice exhibit improved, rather than the expected impaired, hepatic insulin action. This is due to decreased lipogenic gene expression and triglyceride accumulation. The present studies overcome these secondary adaptations by acutely modulating GLP-1R action in HF-fed wild-type mice. The central GLP-1R was targeted given its role as a regulator of hepatic insulin action. We hypothesized that acute inhibition of the central GLP-1R impairs hepatic insulin action beyond the effects of HF feeding. We further hypothesized that activation of the central GLP-1R improves hepatic insulin action in HF-fed mice. Insulin action was assessed in conscious, unrestrained mice using the hyperinsulinemic euglycemic clamp. Mice received intracerebroventricular (icv) infusions of artificial cerebrospinal fluid, GLP-1, or the GLP-1R antagonist exendin-9 (Ex-9) during the clamp. Intracerebroventricular Ex-9 impaired the suppression of hepatic glucose production by insulin, whereas icv GLP-1 improved it. Neither treatment affected tissue glucose uptake. Intracerebroventricular GLP-1 enhanced activation of hepatic Akt and suppressed hypothalamic AMP-activated protein kinase. Central GLP 1R activation resulted in lower hepatic triglyceride levels but did not affect muscle, white adipose tissue, or plasma triglyceride levels during hyperinsulinemia. In response to oral but not intravenous glucose challenges, activation of the central GLP-1R improved glucose tolerance. This was associated with higher insulin levels. Inhibition of the central GLP-1R had no effect on oral or intravenous glucose tolerance. These results show that inhibition of the central GLP-1R deteriorates hepatic insulin action in HF-fed mice but does not affect whole body glucose homeostasis. Contrasting this, activation of the central GLP-1R improves glucose homeostasis in HF-fed mice by increasing insulin levels and enhancing hepatic insulin action. PMID- 22094470 TI - Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression. AB - Since anterior pituitary expresses prolactin receptors, prolactin secreted by lactotropes could exert autocrine or paracrine actions on anterior pituitary cells. In fact, it has been observed that prolactin inhibits its own expression by lactotropes. Our hypothesis is that prolactin participates in the control of anterior pituitary cell turnover. In the present study, we explored the action of prolactin on proliferation and apoptosis of anterior pituitary cells and its effect on the expression of the prolactin receptor. To determine the activity of endogenous prolactin, we evaluated the effect of the competitive prolactin receptor antagonist Delta1-9-G129R-hPRL in vivo, using transgenic mice that constitutively and systemically express this antagonist. The weight of the pituitary gland and the anterior pituitary proliferation index, determined by BrdU incorporation, were higher in transgenic mice expressing the antagonist than in wild-type littermates. In addition, blockade of prolactin receptor in vitro by Delta1-9-G129R-hPRL increased proliferation and inhibited apoptosis of somatolactotrope GH3 cells and of primary cultures of male rat anterior pituitary cells, including lactotropes. These results suggest that prolactin acts as an autocrine/paracrine antiproliferative and proapoptotic factor in the anterior pituitary gland. In addition, anterior pituitary expression of the long isoform of the prolactin receptor, measured by real-time PCR, increased about 10-fold in transgenic mice expressing the prolactin receptor antagonist, whereas only a modest increase in the S3 short-isoform expression was observed. These results suggest that endogenous prolactin may regulate its own biological actions in the anterior pituitary by inhibiting the expression of the long isoform of the prolactin receptor. In conclusion, our observations suggest that prolactin is involved in the maintenance of physiological cell renewal in the anterior pituitary. Alterations in this physiological role of prolactin could contribute to pituitary tumor development. PMID- 22094471 TI - Proton magnetic resonance spectroscopy shows lower intramyocellular lipid accumulation in middle-aged subjects predisposed to familial longevity. AB - Families predisposed to longevity show enhanced glucose tolerance and skeletal muscle insulin sensitivity compared with controls, independent of body composition and physical activity. Intramyocellular lipid (IMCL) accumulation in skeletal muscle has been associated with insulin resistance. Here, we assessed whether subjects enriched for familial longevity have lower IMCL levels. We determined IMCL levels in 48 subjects from the Leiden Longevity Study, comprising 24 offspring of nonagenarian siblings and 24 partners thereof as control subjects. IMCL levels were assessed noninvasively using short echo time proton magnetic resonance spectroscopy ((1)H-MRS) of the tibialis anterior muscle with a 7 Tesla human MR scanner. IMCL levels were calculated relative to the total creatine (tCr) CH3 signal. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). After correction for age, sex, BMI, and physical activity, offspring of long-lived nonagenarian siblings tended to show lower IMCL levels compared with controls (IMCL/tCr: 3.1 +/- 0.5 vs. 4.5 +/- 0.5, respectively, P = 0.051). In a pairwise comparison, this difference reached statistical significance (P = 0.038). We conclude that offspring of nonagenarian siblings predisposed to longevity show lower IMCL levels compared with environmentally matched control subjects. Future research should focus on assessing what mechanisms may explain the lower IMCL levels in familial longevity. PMID- 22094472 TI - Effects of moderate exercise on VLDL1 and Intralipid kinetics in overweight/obese middle-aged men. AB - Prior moderate exercise reduces plasma triglyceride (TG)-rich lipoprotein concentrations, mainly in the large very low-density lipoprotein (VLDL1) fraction, but the mechanism responsible is unclear. We investigated the effects of brisk walking on TG-rich lipoprotein kinetics using a novel method. Twelve overweight/obese middle-aged men underwent two kinetic studies, involving infusion of Intralipid to block VLDL1 catabolism, in random order. On the afternoon prior to infusion, subjects either walked on a treadmill for 2 h at ~50% maximal oxygen uptake or performed no exercise. Multiple blood samples were taken during and after infusion for separation of Intralipid (S(f) 400) and VLDL1 (S(f) 60-400). VLDL1-TG and -apoB production rates were calculated from their linear rises during infusion; fractional catabolic rates (FCR) were calculated by dividing linear rises by fasting concentrations. Intralipid-TG FCR was determined from the postinfusion exponential decay. Exercise reduced fasting VLDL1-TG concentration by 30% (P = 0.007) and increased TG enrichment of VLDL1 particles [30% decrease in cholesteryl ester (CE)/TG ratio (P = 0.007); 26% increase in TG/apoB ratio (P = 0.059)]. Exercise also increased VLDL1-TG, VLDL1-apoB, and Intralipid-TG FCRs by 82, 146, and 43%, respectively (all P < 0.05), but had no significant effect on VLDL1-TG or -apoB production rates. The exercise-induced increase in VLDL1-apoB FCR correlated strongly with the exercise-induced changes in VLDL1 CE/TG (r = -0.659, r = 0.020) and TG/apoB (r = 0.785, P = 0.002) ratios. Thus, exercise-induced reductions in VLDL1 concentrations are mediated by increased catabolism, rather than reduced production, which may be facilitated by compositional changes to VLDL1 particles that increase their affinity for clearance from the circulation. PMID- 22094473 TI - Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice. AB - Low-grade inflammation observed in obesity is a risk factor for cardiovascular disease. Recent studies revealed that this would be linked to gut-derived endotoxemia during fat digestion in high-fat diets, but nothing is known about the effect of lipid composition. The study was designed to test the impact of oil composition of high-fat diets on endotoxin metabolism and inflammation in mice. C57/Bl6 mice were fed for 8 wk with chow or isocaloric isolipidic diets enriched with oils differing in fatty acid composition: milk fat, palm oil, rapeseed oil, or sunflower oil. In vitro, adipocytes (3T3-L1) were stimulated or not with lipopolysaccharide (LPS; endotoxin) and incubated with different fatty acids. In mice, the palm group presented the highest level of IL-6 in plasma (P < 0.01) together with the highest expression in adipose tissue of IL-1beta and of LPS sensing TLR4 and CD14 (P < 0.05). The higher inflammation in the palm group was correlated with a greater ratio of LPS-binding protein (LBP)/sCD14 in plasma (P < 0.05). The rapeseed group resulted in higher sCD14 than the palm group, which was associated with lower inflammation in both plasma and adipose tissue despite higher plasma endotoxemia. Taken together, our results reveal that the palm oil based diet resulted in the most active transport of LPS toward tissues via high LBP and low sCD14 and the greatest inflammatory outcomes. In contrast, a rapeseed oil-based diet seemed to result in an endotoxin metabolism driven toward less inflammatory pathways. This shows that dietary fat composition can contribute to modulate the onset of low-grade inflammation through the quality of endotoxin receptors. PMID- 22094474 TI - Evaluation of safety monitoring guidelines based on MRI lesion activity in multiple sclerosis. AB - OBJECTIVE: We evaluate variants of a commonly used data safety monitoring guideline in clinical trials in multiple sclerosis (MS) that flags patients who, at a follow-up visit, have 5 or more contrast-enhancing lesions (CELs) above their baseline count. METHODS: We apply the guideline to a relapsing cohort and a secondary progressive cohort. We assess the number of patients that meet the guideline and describe the characteristics of these patients; we also examine the value of the guideline in predicting relapse occurrence in the 28 days following that MRI. These analyses were repeated for thresholds varying from 1 to 10 CELs above baseline. RESULTS: Between 4% and 6% of patients met the threshold of 5 in both cohorts; patients with higher baseline counts and higher T2 lesion burden were more apt to meet the threshold. After adjustment for other covariates, the odds ratio (OR) of relapse associated with meeting the threshold is significant (p < 0.05) or near significant (0.05 <= p < 0.10) for thresholds between 5 and 8 for the relapsing cohort, but not for the secondary progressive cohort. Across thresholds, the adjusted OR is consistently greater than 1, and there is an increasing trend as the threshold increases from 1 to 7. CONCLUSIONS: A guideline based on crossing a threshold CEL count above baseline may be valuable in monitoring patient safety. Further study should be conducted using different datasets to assess the generalizability of these results. PMID- 22094475 TI - Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. AB - OBJECTIVE: To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning. METHODS: We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 +/- 2.2 years for patients and 5.5 +/- 3.0 for carrier relatives). RESULTS: Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives. CONCLUSIONS: Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS. PMID- 22094476 TI - Evaluating patients with TIA: to hospitalize or not to hospitalize? PMID- 22094477 TI - Should TIA patients be hospitalized or referred to a same-day clinic?: a decision analysis. AB - OBJECTIVE: For patients presenting with TIA, a previous study concluded that hospitalization is cost-effective compared to discharge without treatment from the emergency department. We performed a cost-effectiveness analysis of hospitalization vs urgent clinic evaluation following TIA. METHODS: Among a cohort of TIA patients, we created a decision tree model to compare the decision to hospitalize or refer to urgent-access specialty clinic. We estimated probabilities, utilities, and direct costs from the available literature and calculated incremental cost-effectiveness ratio (ICER). We assumed equal access to standard medical treatments between the 2 approaches; however, we estimated higher tissue plasminogen activator (tPA) utilization among hospitalized patients. We performed sensitivity analyses to assess all assumptions in our model. RESULTS: In patients with TIA aged 65-74 years, hospitalization yielded additional 0.00026 quality-adjusted life-years (QALYs) at 1 year, but at an additional cost of $5,573 per patient compared to urgent clinic evaluation (ICER = $21,434,615/QALY). Over 30 years, the ICER was $3,473,125/QALY. These results were not sensitive to varying 48-hour stroke risk, length of stay, tPA utilization rate, QALYs saved per tPA treatment, and hospitalization and clinic costs, and cost saved per tPA treatment. CONCLUSION: Despite increased access to tPA in the hospital, we found that hospitalization is not cost-effective compared to same-day clinic evaluation following TIA. A very small fraction of patients benefits from hospitalization if urgent-access TIA clinics are available. The widespread development of urgent-access TIA clinics is warranted. PMID- 22094478 TI - Does one guideline fit all? PMID- 22094479 TI - Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus. AB - BACKGROUND: Patients with concomitant diabetes mellitus (DM) and prior stroke (PS) were excluded from European approval of alteplase in stroke. We examined the influence of DM and PS on the outcomes of patients who received thrombolytic therapy (T; data from Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register) compared to nonthrombolyzed controls (C; data from Virtual International Stroke Trials Archive). METHODS: We selected ischemic stroke patients on whom we held data on age, baseline NIH Stroke Scale score (NIHSS), and 90-day modified Rankin Scale score (mRS). We compared the distribution of mRS between T and C by Cochran-Mantel-Haenszel (CMH) test and proportional odds logistic regression, after adjustment for age and baseline NIHSS, in patients with and without DM, PS, or the combination. We report odds ratios (OR) for improved distribution of mRS with 95% confidence interval (CI) and CMH p value. RESULTS: Data were available for 29,500 patients: 5,411 (18.5%) had DM, 5,019 had PS (17.1%), and 1,141 (5.5%) had both. Adjusted mRS outcomes were better for T vs C among patients with DM (OR 1.45 [1.30-1.62], n = 5,354), PS (OR 1.55 [1.40-1.72], n = 4,986), or concomitant DM and PS (OR 1.23 [0.996 1.52], p = 0.05, n = 1,136), all CMH p < 0.0001. These are comparable to outcomes between T and C among patients with neither DM nor PS: OR = 1.53 (1.42-1.63), p < 0.0001, n = 19,339. There was no interaction on outcome between DM and PS with alteplase treatment (tissue plasminogen activator * DM * PS, p = 0.5). Age <=80 years or >80 years did not influence our findings. CONCLUSIONS: Outcomes from thrombolysis are better than the controls among patients with DM, PS, or both. We find no statistical justification for the exclusion of these patients from receiving thrombolytic therapy. PMID- 22094480 TI - Long-term association between seizure outcome and depression after resective epilepsy surgery. AB - OBJECTIVE: This study explored the association between long-term epilepsy surgery outcome and changes in depressive symptoms. METHODS: Adults were enrolled between 1996 and 2001 in a multicenter prospective study to evaluate outcomes of resective epilepsy surgery. The extent of depressive symptoms and depression case status (none, mild, or moderate/severe) were assessed using the Beck Depression Inventory (BDI) preoperatively and 3, 12, 24, 48, and 60 months postoperatively. A mixed-model repeated-measures analysis was performed, adjusting for covariates of seizure location, gender, age, race, education, and seizure control. RESULTS: Of the total 373 subjects, 256 were evaluated at baseline and 5 years after surgery. At baseline, 164 (64.1%) were not depressed, 34 (13.3%) were mildly depressed, and 58 (22.7%) had moderate to severe depression. After 5 years, 198 (77.3%) were not depressed, 20 (7.8%) were mildly depressed, and 38 (14.8%) were moderately to severely depressed. Five years after surgery, the reduction in mean change from baseline in BDI score was greater in subjects with excellent seizure control than in the fair and poor seizure control groups (p = 0.0006 and p = 0.02 respectively). Those with good seizure control had a greater reduction in BDI score than the poor seizure control group (p = 0.02) and borderline significant reduction compared with the fair seizure control group (p = 0.055). CONCLUSION: Although study participants had initial improvement in depressive symptoms, on average, after resective surgery, only patients with good or excellent seizure control had sustained long-term improvement in mood. PMID- 22094482 TI - An autopsy case of SOD1-related ALS with TDP-43 positive inclusions. PMID- 22094481 TI - Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease. AB - OBJECTIVE: We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls. METHODS: Fifteen patients with AD (mean age 72 +/- 6 years, Mini-Mental State Examination score [MMSE] 20 +/- 6) and 19 age-matched controls (mean age 68 +/- 6 years, MMSE 29 +/- 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. RESULTS: Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. CONCLUSIONS: Our voxel-wise results indicated that ASL-MRI provides largely overlapping information with FDG-PET. ROI analysis demonstrated that both modalities detected similar degrees of functional deficits in affected areas. Given its ease of acquisition and noninvasiveness, ASL-MRI may be an appealing alternative for AD studies. PMID- 22094483 TI - Reducing bodies and myofibrillar myopathy features in FHL1 muscular dystrophy. AB - OBJECTIVE: Some pathologic features of the FHL1 myopathies and the myofibrillar myopathies (MFMs) overlap; we therefore searched for mutations in FHL1 in our cohort of 50 patients with genetically undiagnosed MFM. METHODS: Mutations in FHL1 were identified by direct sequencing. Polymorphisms were excluded by using allele-specific PCR in 200 control subjects. Structural changes in muscle were analyzed by histochemistry, immunocytochemistry, and electron microscopy. RESULTS: We detected 2 novel and 1 previously identified missense mutation in 5 patients. Patients 1-4 presented before age 30, display menadione-nitro blue tetrazolium-positive reducing bodies, and harbor mutations in the FHL1 LIM2 domain. Patient 5 presented at age 75 and has no reducing bodies, and his mutation is not in a LIM domain. The clinical features include progressive muscle weakness, hypertrophied muscles, rigid spine, and joint contractures, and 1 patient also has peripheral neuropathy. High-resolution electron microscopy reveals the reducing bodies composed of 13-nm tubulofilaments initially emanating from Z-disks. At a more advanced stage, abundant reducing bodies appear in the cytoplasm and nuclei with concomitant myofibrillar disintegration, accumulation of cytoplasmic degradation products, and aggregation of endoplasmic reticulum and sarcotubular profiles. CONCLUSIONS: FHL1 dystrophies can be associated with MFM pathology. Mutations in the LIM2 domain are associated with reducing bodies composed of distinct tubulofilaments. A mutation extraneous to LIM domains resulted in a mild late-onset phenotype with MFM pathology but no reducing bodies. PMID- 22094484 TI - Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype. AB - OBJECTIVES: Acetazolamide has been the most commonly used treatment for hypokalemic periodic paralysis since 1968. However, its mechanism of efficacy is not fully understood, and it is not known whether therapy response relates to genotype. We undertook a clinical and genetic study to evaluate the response rate of patients treated with acetazolamide and to investigate possible correlations between response and genotype. METHODS: We identified a total of 74 genotyped patients for this study. These included patients who were referred over a 15-year period to the only U.K. referral center or to a Chinese center and who underwent extensive clinical evaluation. For all genotyped patients, the response to acetazolamide therapy in terms of attack frequency and severity was documented. Direct DNA sequencing of CACNA1S and SCN4A was performed. RESULTS: Only 46% of the total patient cohort (34 of 74) reported benefit from acetazolamide. There was a greater chance of benefit in patients with mutations in CACNA1S (31 responded of 55 total) than in those with mutations in SCN4A (3 responded of 19 total). Patients with mutations that resulted in amino acids being substituted by glycine in either gene were the least likely to report benefit. CONCLUSIONS: This retrospective study indicates that only approximately 50% of genotyped patients with hypokalemic periodic paralysis respond to acetazolamide. We found evidence supporting a relationship between genotype and treatment response. Prospective randomized controlled trials are required to further evaluate this relationship. Development of alternative therapies is required. PMID- 22094485 TI - Challenging the validity of imposing contraindications to thrombolysis for acute ischemic stroke. PMID- 22094486 TI - Caval flow reflects Fontan hemodynamics: quantification by magnetic resonance imaging. AB - INTRODUCTION: Failing Fontan circulation is a multifactorial problem without clear predictors and with uncertain onset. We sought to investigate the correlations between systemic venous flow return and the clinical condition of Fontan patients. METHODS: Flow measurements using phase contrast magnetic resonance imaging (MRI) were performed in the superior and inferior vena cava (SVC, IVC) in 61 Fontan patients. Median postoperative follow-up time was 6.7 (0.6-14.1) years; median age at MRI was 11.6 (4.0-44.6) years. Eight patients were identified clinically as a subgroup with suboptimal hemodynamics. The effective forward flow of combined SVC and IVC flow volume was defined as the venous cardiac index (vCI, l/min/m(2)). SVC flow ratio was defined as SVC flow in relation to vCI. The vCI and flow distribution between the SVC and IVC were investigated in relation to the hemodynamics and patients' age at MRI. RESULTS: Venous flow return through the SVC was 1.1 (0.6-3.4) l/min/m(2) and through the IVC 1.8 (0.6-3.2) l/min/m(2); total vCI was 3 l/min/m(2) (1.2-5.1). Patients with suboptimal Fontan hemodynamics showed significantly lower IVC flow return (median of 1.5 vs. 1.9 l/min/m(2), p = 0.027) and increased SVC flow ratio (0.56 vs. 0.35, p = 0.005) in comparison to those with good clinical condition. The total vCI decrease was correlated with older patient age (r = 0.575, p < 0.001). CONCLUSIONS: Altered systemic venous flow return is associated with suboptimal Fontan hemodynamics and seems to progress with patients' age and long-term follow up after Fontan operation. Thus, MRI flow volume measurements might help in monitoring Fontan patients before the onset of clinical signs of suboptimal hemodynamics. PMID- 22094487 TI - Soy protein preserves basement membrane integrity through a synergistic effect on nephrin, matrix metalloproteinase and vascular endothelial growth factor. AB - BACKGROUND/AIMS: Soy protein improves renal function and prevents albuminuria in diabetic rats. This study investigates whether the renoprotective effect of soy protein is related to sustenance of basement membrane integrity. METHODS: Adult male albino rats were randomized into four groups and fed one of the following semi-synthetic diets consisting of corn starch (60%) and casein (20%; CCD), fructose (60%) and casein (20%; FCD), fructose (60%) and soy protein (20%; FSD), or corn starch (60%) and soy protein (20%; CSD). Plasma chemistry and renal changes were analyzed after 60 days. RESULTS: FCD rats displayed metabolic derangements and renal ultrastructural changes. FSD rats showed reduction in type IV collagen, tissue inhibitor for matrix metallo-proteinase-2, vascular endothelial growth factor and tumor necrosis factor-alpha expression and improved matrix metallo-proteinase expression. Renal architecture was preserved in these rats. CONCLUSION: Soy protein supplementation not only improved insulin sensitivity but also markedly attenuated renal basement membrane changes in fructose diet-fed rats. These findings provide evidence in support of the use of dietary soy protein in patients with diabetic kidney disease. PMID- 22094488 TI - A comparison of two-fingers technique and two-thumbs encircling hands technique of chest compression in neonates. AB - OBJECTIVE: To compare the proportion of correct placements (POCP) between 'two fingers' and 'two-thumbs' techniques of chest compression among neonates of various gestations. STUDY DESIGN: Two-fingers and two-thumbs spans of 32 adult rescuers were individually compared with the inter-nipple line to sterno-xiphoid junction distance of 39 neonates. 'Correct placement' was defined if two fingers/two-thumbs span was equal to or less than the inter-nipple line to sterno xiphoid junction distance. The POCPs was compared between two-fingers and two thumbs methods of chest compression by the McNemar test among neonates and their various subgroups. RESULT: There were a total of 1248 comparisons. The POCPs with two-fingers and two-thumbs techniques were 6.7 and 77% in all neonates, 10.6 and 89.5% in full term and 1.2 and 59% in preterm neonates, respectively (P<0.001). CONCLUSION: Two-thumbs technique achieved higher POCPs and should be preferred over two-fingers technique among neonates. PMID- 22094489 TI - Decreased survival in necrotizing enterocolitis is significantly associated with neonatal and maternal blood group: the AB isoagglutinin hypothesis. AB - OBJECTIVE: To determine the effect of neonatal and maternal blood group on the mortality risk from necrotizing enterocolitis (NEC). STUDY DESIGN: Retrospective chart review of all neonates admitted to the neonatal intensive care unit over 24 years. Data on birth date, gestational age, maternal/neonatal blood group, number of transfusions, and survival time (defined as date of birth to date of death/discharge) were collected on those with NEC. RESULT: 276 neonates with Bell stage II-III NEC were analyzed. AB neonates had a significantly higher risk of mortality from NEC compared with other blood groups (HR 2.87; 95% CI 1.40 to 5.89; P=0.003). Multivariate analysis showed AB blood group to be an independent risk factor for mortality from NEC. CONCLUSION: Neonatal and maternal blood groups are significantly associated with a neonate's survival from NEC. The increased mortality of AB neonates may be related to factors such as neonatal blood group antigens and/or transplacental transfer of isoagglutinins. PMID- 22094490 TI - Cardiovascular instability after patent ductus arteriosus ligation in preterm infants: the role of hydrocortisone. AB - OBJECTIVE: Following patent ductus arteriosus (PDA) ligation, preterm infants may develop profound hypotension and respiratory failure. Prophylactic stress hydrocortisone (HC) has emerged as a therapy to prevent complications, postulating these infants do not synthesize steroids because of an immature hypothalamic-pituitary-adrenal axis. The purpose of this study was to compare outcomes in infants who received stress HC before their PDA ligations to those who did not. STUDY DESIGN: A retrospective chart review was performed of infants who underwent PDA ligations at our institution's neonatal intensive care unit. Data were collected on treatment with HC, and respiratory and cardiovascular support. RESULT: Gestational age (GA) and birth weight were lower in the HC group (24 vs 25 weeks, 632 vs 790 g), but age at time of surgery was similar (26 vs 21 days). Cardiorespiratory support was comparable between the groups pre- and post operatively. In regression models that adjusted for GA, HC treatment was not independently related to respiratory support postoperatively, but was associated with a decrease in postoperative dopamine (2.2 mcg kg(-1) min(-1); P=0.03). Respiratory support postoperatively was predicted by preoperative respiratory support. GA and age at surgery were not independently associated with outcome. CONCLUSION: Preoperative stress HC was not associated with improved cardiorespiratory stability, regardless of GA. Further investigation is needed to identify infants who may benefit from this therapy. PMID- 22094491 TI - Four wishes for Aubrey. AB - In the critical care environment, what begins as cure-oriented and life-extending treatment may become unsuccessful in overcoming the patient's increasingly complex pathophysiology. A case from the neonatal intensive care unit is presented and used to elaborate upon care transitions toward palliative and supportive care that can be rendered in the hospital, at home or in a hospice facility. Successful transitions may rest upon anticipatory guidance by the primary physician and team, or a consultant, to facilitate and enable parents and team members alike in addressing the hard realities that cure, or even successful ICU discharge, is unlikely. A simple mechanism of addressing and accommodating a family's wishes is provided. PMID- 22094492 TI - Randomized controlled trial of magnesium sulfate in women at risk of preterm delivery-neonatal cardiovascular effects. AB - OBJECTIVE: Use of antenatal magnesium sulfate (MgSO(4)) may reduce cerebral palsy in infants born very preterm. Low systemic blood flow in the first day in very preterm infants has been associated with cerebral injury and adverse motor outcome. The aim was to determine the effect of MgSO(4) on systemic blood flow in preterm infants. STUDY DESIGN: Randomized trial of MgSO(4) versus saline placebo given to mothers at risk of delivery before 30 weeks gestation. Echocardiographic monitoring performed at 3 to 5, 10 to 12 and 24 h. RESULT: A total of 48 infants were exposed to MgSO(4) and 39 to placebo. Infants exposed to MgSO(4) were significantly more likely to receive volume expansion (42% versus 21%). Inotrope use did not differ significantly (40% versus 26%). There was no significant difference in mean lowest superior vena cava (SVC) flow or right ventricular output (RVO), or incidence of low SVC flow or RVO in the first 24 h. Infants exposed to MgSO(4) had a significantly higher heart rate and were more likely to have low SVC flow at 10 to 12 h but not other times. CONCLUSION: Antenatal MgSO(4) produced no consistent cardiovascular effects in the infant in the first 24 h. There is no evidence from this study to suggest the mechanism by which antenatal MgSO(4) prevents cerebral palsy is through a cardiovascular effect in the newborn. PMID- 22094493 TI - Predischarge non-invasive risk assessment for prediction of significant hyperbilirubinemia in term and late preterm neonates. AB - OBJECTIVE: To evaluate efficacy of predischarge transcutaneous bilirubin (TcB) measurement and clinical risk assessment in predicting hyperbilirubinemia needing treatment. STUDY DESIGN: A diagnostic test was performed in a prospective cohort study conducted at a teaching hospital in North India. Subjects included healthy neonates with a gestation period of >=35 weeks or birth weight >=2000 g. Maternal, neonatal and delivery risk factors for hyperbilirubinemia were prospectively collected. TcB was measured in all enrolled neonates at 24+/-6, 72 to 96 and 96 to 144 h of postnatal age and when indicated clinically. Neonates were followed up during hospital stay and after discharge till completion of the 7th postnatal day. The key outcome was significant hyperbilirubinemia defined as need of phototherapy on the basis of modified American Academy of Pediatrics guidelines. In neonates born at >=38 weeks of gestation and in neonates born at <=37 completed weeks of gestation, middle line and lower line of phototherapy thresholds were used to initiate phototherapy, respectively. Variables observed to be significantly associated with significant hyperbilirubinemia on multivariate analysis were used for construction of a clinical risk assessment tool. Predictive ability of the risk assessment tool was assessed by calculating sensitivity, specificity, positive predictive value and negative predictive value, by plotting receiver-operating characteristics curve and calculating c statistic. RESULT: A total of 997 neonates (birth weight: 2627+/-536 g, gestation: 37.8+/-1.5 weeks) were enrolled in the study, of which 931 completed follow-up. Among enrolled neonates, 344 (34.5%) were low birth weight. Overall, a total of 199 (20%) neonates developed significant hyperbilirubinemia. On stepwise logistic regression analysis, predischarge TcB percentile and gestation were significantly found to be associated with significant hyperbilirubinemia. A risk assessment graph was constructed to predict subsequent development of significant hyperbilirubinemia. Area under curve for this risk assessment strategy was 0.75. CONCLUSION: A risk assessment graphical tool consisting of TcB and gestation accurately predicted subsequent need of phototherapy. Further studies are needed to validate performance of this risk assessment tool. PMID- 22094494 TI - Umbilical cord milking in term infants delivered by cesarean section: a randomized controlled trial. AB - OBJECTIVE: The study's objective was to compare hematocrit (Hct) levels at 36 to 48 h of age in term infants delivered by cesarean section exposed to immediate cord clamping or umbilical cord milking (UCM). STUDY DESIGN: In this randomized controlled trial, 24 women scheduled for elective cesarean section were randomized to either immediate clamping (<10 s) or UCM (milked * 5 by the obstetrical provider) at birth. RESULT: All subjects received their allocated intervention. The milking group had a smaller placental residual blood volume (13.2+/-5.6 vs 19.2+/-5.4 ml kg(-1), P=0.01) and higher Hct levels at 36 to 48 h (57.5+/-6.6 vs 50.0+/-6.4 %, P=0.01). Five infants (42%) in the immediate group had a Hct of <=47%, indicative of anemia. CONCLUSION: UCM results in placental transfusion in term infants at the time of elective cesarean section with higher Hct levels at 36 to 48 h of age. PMID- 22094495 TI - Circulating CD133: a promising biomarker, but what are we measuring? PMID- 22094496 TI - Right paraesophageal lymph node dissection in papillary thyroid carcinoma. AB - BACKGROUND: This study was designed to identify the patients with papillary thyroid carcinoma (PTC) who would benefit from RPELN dissection. SUMMARY BACKGROUND DATA: The value of the right paraesophageal lymph nodes (RPELNs), which are located posterior to the right recurrent laryngeal nerve, may be underestimated. Although the RPELNs are common sites of nodal recurrence, few related studies have been reported. METHODS: We retrospectively reviewed the medical records of 369 patients (286 female, 83 male) who underwent total thyroidectomy (327 patients) or right lobectomy (42 patients) with therapeutic or prophylactic central lymph node dissection for primary PTC between August 2008 and January 2010 at the Department of Surgery, Samsung Medical Center. RESULTS: Central lymph node (CLN) metastases were present in 51.2% (189 of 369) of the patients, and RPELN metastases were present in 12.2% (45 of 369) of the patients. The rate of RPELN metastasis was 19.6% (37 of 189) in patients with CLN metastases, but only 4.4% (8 of 180) in patients with no CLN metastases (P < .001). A univariate analysis revealed that RPELN metastasis was significantly correlated with the size of the tumor, the perithyroidal extent (capsular invasion), CLN metastasis, and lateral lymph node metastases. There were no significant differences in terms of gender, mean age, or number of tumors between groups. A multivariate analysis revealed that tumor size (>1 cm) and number of CLN metastases (>= 3) were significantly correlated with RPELN metastasis. CONCLUSIONS: RPELN dissection should be considered in patients with right thyroid cancer, tumors larger than 1 cm, or multiple CLN metastases. PMID- 22094497 TI - The impact of comorbid [corrected] conditions on critical illness. AB - OBJECTIVE: To review the current knowledge of common comorbidities in the intensive care unit, including diabetes mellitus, chronic obstructive pulmonary disease, cancer, end-stage renal disease, end-stage liver disease, HIV infection, and obesity, with specific attention to epidemiology, contribution to diseases and outcomes, and the impact on treatments in these patients. DATA SOURCE: Review of the relevant medical literature for specific common comorbidities in the critically ill. RESULTS: Critically ill patients are admitted to the intensive care unit for various reasons, and often the admission diagnosis is accompanied by a chronic comorbidity. Chronic comorbid conditions commonly seen in critically ill patients may influence the decision to provide intensive care unit care, decisions regarding types and intensity of intensive care unit treatment options, and outcomes. The presence of comorbid conditions may predispose patients to specific complications or forms of organ dysfunction. The impact of specific comorbidities varies among critically ill medical, surgical, and other populations, and outcomes associated with certain comorbidities have changed over time. Specifically, outcomes for patients with cancer and HIV have improved, likely related to advances in therapy. Overall, the negative impact of chronic comorbidity on survival in critical illness may be primarily influenced by the degree of organ dysfunction or the cumulative severity of multiple comorbidities. CONCLUSION: Chronic comorbid conditions are common in critically ill patients. Both the acute illness and the chronic conditions influence prognosis and optimal care delivery for these patients, particularly for adverse outcomes and complications influenced by comorbidities. Further work is needed to fully determine the individual and combined impact of chronic comorbidities on intensive care unit outcomes. PMID- 22094498 TI - Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials. AB - OBJECTIVES: To summarize randomized controlled trials on the effects of sedative agents on neurologic outcome, mortality, intracranial pressure, cerebral perfusion pressure, and adverse drug events in critically ill adults with severe traumatic brain injury. DATA SOURCES: PubMed, MEDLINE, EMBASE, the Cochrane Database, Google Scholar, two clinical trials registries, personal files, and reference lists of included articles. STUDY SELECTION: Randomized controlled trials of propofol, ketamine, etomidate, and agents from the opioid, benzodiazepine, alpha-2 agonist, and antipsychotic drug classes for management of adult intensive care unit patients with severe traumatic brain injury. DATA EXTRACTION: In duplicate and independently, two investigators extracted data and evaluated methodologic quality and results. DATA SYNTHESIS: Among 1,892 citations, 13 randomized controlled trials enrolling 380 patients met inclusion criteria. Long-term sedation (>=24 hrs) was addressed in six studies, whereas a bolus dose, short infusion, or doubling of plasma drug concentration was investigated in remaining trials. Most trials did not describe baseline traumatic brain injury prognostic factors or important cointerventions. Eight trials possibly or definitely concealed allocation and six were blinded. Insufficient data exist regarding the effects of sedative agents on neurologic outcome or mortality. Although their effects are likely transient, bolus doses of opioids may increase intracranial pressure and decrease cerebral perfusion pressure. In one study, a long-term infusion of propofol vs. morphine was associated with a reduced requirement for intracranial pressure-lowering cointerventions and a lower intracranial pressure on the third day. Trials of propofol vs. midazolam and ketamine vs. sufentanil found no difference between agents in intracranial pressure and cerebral perfusion pressure. CONCLUSIONS: This systematic review found no convincing evidence that one sedative agent is more efficacious than another for improvement of patient-centered outcomes, intracranial pressure, or cerebral perfusion pressure in critically ill adults with severe traumatic brain injury. High bolus doses of opioids, however, have potentially deleterious effects on intracranial pressure and cerebral perfusion pressure. Adequately powered, high-quality, randomized controlled trials are urgently warranted. PMID- 22094499 TI - Walk this way. PMID- 22094500 TI - Airway pressure release ventilation: a mode of ventilation to consider in children with congenital heart disease. PMID- 22094501 TI - Go team go: recognizing the importance of team training in critical care. PMID- 22094502 TI - Away from the precipice. PMID- 22094503 TI - Nutritional support in critically ill patients: can we have the cake and the topping too? PMID- 22094504 TI - Ultrasonographic evaluation of diaphragmatic function. PMID- 22094505 TI - High-frequency oscillatory ventilation in adult patients with acute respiratory distress syndrome: where do we stand and where should we go? PMID- 22094506 TI - More randomized controlled trials in acute lung injury? Not so fast, my friend. PMID- 22094507 TI - Defining acute kidney injury: further steps in the right direction but can detente be maintained? PMID- 22094508 TI - Timing of fluid administration in critically ill patients with acute kidney injury: every good thing has an end. PMID- 22094509 TI - Sepsis and hypotension: enter kynurenine, move over nitric oxide. PMID- 22094510 TI - Can we reliably predict the development of hospital acquired infections after septic shock? PMID- 22094511 TI - Supplemental parenteral nutrition in the critically ill: "different strokes for different folks". PMID- 22094512 TI - Is there a role for soluble guanylate cyclase stimulators in acute pulmonary embolism? PMID- 22094514 TI - Central role of oxidative stress and its signaling pathways in causing and preventing acute lung injury. PMID- 22094513 TI - Sodium nitroprusside-enhanced cardiopulmonary resuscitation: are we out of the box yet? PMID- 22094515 TI - World Federation of Neurologic Surgeons grade V ... rationed care or rational care? PMID- 22094516 TI - To count for--mortality on intensive care unit and the allocation of ventilator associated pneumonia. PMID- 22094517 TI - Sedating the injured brain: searching for the "ideal" pharmacological recipe. PMID- 22094518 TI - Mass critical care for children: implications for adult critical care. PMID- 22094519 TI - Advocacy to extend the use of continuous noninvasive hemoglobin measurement. PMID- 22094521 TI - Selective digestive decontamination reduces bacteremia following eradication of gut overgrowth. PMID- 22094523 TI - The importance of source identification in septic patients. PMID- 22094525 TI - Respiratory dialysis is not extracorporeal membrane oxygenation. PMID- 22094528 TI - Confusion between gamma-linolenic acid and gamma-linoleic acid. PMID- 22094530 TI - Psychiatric long-term complications of intensive care unit survivors. PMID- 22094532 TI - Comment on: "Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice" (Magnani P, Conforti A, Zanolin E, Marzotto M and Bellavite P, Psychopharmacology, 2010). PMID- 22094531 TI - The effects of acute tryptophan depletion on costly information sampling: impulsivity or aversive processing? AB - RATIONALE: The neurotransmitter serotonin (5-HT) has been implicated in both aversive processing and impulsivity. Reconciling these accounts, recent studies have demonstrated that 5-HT is important for punishment-induced behavioural inhibition. These studies focused on situations where actions lead directly to punishments. However, decision-making often involves making tradeoffs between small 'local' costs and larger 'global' losses. OBJECTIVE: We aimed to distinguish whether 5-HT promotes avoidance of local losses, global losses, or both, in contrast to an overall effect on reflection impulsivity. We further examined the influence of individual differences in sub-clinical depression, anxiety and impulsivity on global and local loss avoidance. METHODS: Healthy volunteers (N = 21) underwent an acute tryptophan depletion procedure in a double blind, placebo-controlled crossover design. We measured global and local loss avoidance in a decision-making task where subjects could sample information at a small cost to avoid making incorrect decisions, which resulted in large losses. RESULTS: Tryptophan depletion removed the suppressive effects of small local costs on information sampling behaviour. Sub-clinical depressive symptoms produced effects on information sampling similar to (but independent from) those of tryptophan depletion. Dispositional anxiety was related to global loss avoidance. However, trait impulsivity was unrelated to information sampling. CONCLUSIONS: The current findings are consistent with recent theoretical work that characterises 5-HT as pruning a tree of potential decisions, eliminating options expected to lead to aversive outcomes. Our results extend this account by proposing that 5-HT promotes reflexive avoidance of relatively immediate aversive outcomes, potentially at the expense of more globally construed future losses. PMID- 22094533 TI - Marginal hazard regression for correlated failure time data with auxiliary covariates. AB - In many biomedical studies, it is common that due to budget constraints, the primary covariate is only collected in a randomly selected subset from the full study cohort. Often, there is an inexpensive auxiliary covariate for the primary exposure variable that is readily available for all the cohort subjects. Valid statistical methods that make use of the auxiliary information to improve study efficiency need to be developed. To this end, we develop an estimated partial likelihood approach for correlated failure time data with auxiliary information. We assume a marginal hazard model with common baseline hazard function. The asymptotic properties for the proposed estimators are developed. The proof of the asymptotic results for the proposed estimators is nontrivial since the moments used in estimating equation are not martingale-based and the classical martingale theory is not sufficient. Instead, our proofs rely on modern empirical process theory. The proposed estimator is evaluated through simulation studies and is shown to have increased efficiency compared to existing methods. The proposed method is illustrated with a data set from the Framingham study. PMID- 22094535 TI - Connecting MU-fluidics to electron microscopy. AB - A versatile methodology for electron microscopy (EM) grid preparation enabling total content sample analysis is presented. A microfluidic-dialysis conditioning module to desalt or mix samples with negative stain solution is used, combined with a robotic writing table to micro-pattern the EM grids. The method allows heterogeneous samples of minute volumes to be processed at physiological pH for structure and mass analysis, and allows the preparation characteristics to be finely tuned. PMID- 22094534 TI - Isotonic estimation of survival under a misattribution of cause of death. AB - Several authors have indicated that incorrectly classified cause of death for prostate cancer survivors may have played a role in the observed recent peak and decline of prostate cancer mortality. Motivated by the suggestion we studied a competing risks model where other cause of death may be misattributed as a death of interest. We first consider a naive approach using unconstrained nonparametric maximum likelihood estimation (NPMLE), and then present the constrained NPMLE where the survival function is forced to be monotonic. Surprising observations were made as we studied their small-sample and asymptotic properties in continuous and discrete situations. Contrary to the common belief that the non monotonicity of a survival function NPMLE is a small-sample problem, the constrained NPMLE is asymptotically biased in the continuous setting. Other isotonic approaches, the supremum (SUP) method and the Pooled-Adjacent-Violators (PAV) algorithm, and the EM algorithm are also considered. We found that the EM algorithm is equivalent to the constrained NPMLE. Both SUP method and PAV algorithm deliver consistent and asymptotically unbiased estimator. All methods behave well asymptotically in the discrete time setting. Data from the Surveillance, Epidemiology and End Results (SEER) database are used to illustrate the proposed estimators. PMID- 22094536 TI - "Asymmetric scalloping of the regenerate": a radiological sign of pseudoaneurysm in distraction osteogenesis. AB - Pseudoaneurysm formation is an uncommon but well-recognised and important complication in limb reconstruction surgery. Postoperative diagnosis is usually clinical or an incidental finding. We present an 11-year-old girl, who underwent two-stage limb lengthening with a circular fixator, for a previously treated pseudoarthrosis of the tibia. During the lengthening plan, a concave defect was noted on one side of the regenerate, which was found to be due to extrinsic compression by a pseudoaneurysm. Normal regenerate formation was seen after selective embolisation of the pseudoaneurysm. This concave appearance on one side of the regenerate has previously been described secondary to a difference in stability on the two sides of the osteotomy, when a monolateral fixator is used, but not due to extrinsic compression by a pseudoaneurysm. The authors propose that this radiographic appearance of "asymmetrical scalloping" on one side of the regenerate may represent a radiological sign of a pseudoaneurysm formation and should provoke investigation for the same. PMID- 22094538 TI - The nature and course of sensory changes following spinal cord injury: predictive properties and implications on the mechanism of central pain. AB - Central pain below the injury level after spinal cord injury is excruciating, chronic and resistive to treatment. Animal studies suggest that pretreatment may prevent central pain, but to date there are no measures to predict its development. Our aim was to monitor changes in the sensory profile below the lesion prior to the development of below-level central pain in order to search for a parameter that could predict its risk and to further explore its pathophysiology. Thirty patients with spinal cord injury and 27 healthy controls underwent measurement of warm, cold, heat-pain and touch thresholds as well as graphaesthesia, allodynia, hyperpathia and wind-up pain in intact region and in the shin and feet (below level). Patients were tested at 2-4 weeks, 1-2.5 months and 2.5-6 months after the injury or until central pain had developed. At the end of the follow-up, 46% of patients developed below-level central pain. During the testing periods, individuals who eventually developed central pain had higher thermal thresholds than those who did not and displayed high rates of abnormal sensations (allodynia and hyperpathia), which gradually increased with time until central pain developed. Logistic regressions revealed that the best predictor for the risk of below-level central pain was allodynia in the foot in the second testing session with a 77% probability (90.9% confidence). The results suggest that neuronal hyperexcitability, which may develop consequent to damage to spinothalamic tracts, precedes central pain. Furthermore, it appears that below level central pain develops after a substantial build-up of hyperexcitability. To the best of our knowledge, this is the first systematic report establishing that neuronal hyperexcitability precedes central pain. Predicting the risk for central pain can be utilized to initiate early treatment in order to prevent its development. PMID- 22094537 TI - Colony-stimulating factor-1 mediates macrophage-related neural damage in a model for Charcot-Marie-Tooth disease type 1X. AB - Previous studies in our laboratory have shown that in models for three distinct forms of the inherited and incurable nerve disorder, Charcot-Marie-Tooth neuropathy, low-grade inflammation implicating phagocytosing macrophages mediates demyelination and perturbation of axons. In the present study, we focus on colony stimulating factor-1, a cytokine implicated in macrophage differentiation, activation and proliferation and fostering neural damage in a model for Charcot Marie-Tooth neuropathy 1B. By crossbreeding a model for the X-linked form of Charcot-Marie-Tooth neuropathy with osteopetrotic mice, a spontaneous null mutant for colony-stimulating factor-1, we demonstrate a robust and persistent amelioration of demyelination and axon perturbation. Furthermore, functionally important domains of the peripheral nervous system, such as juxtaparanodes and presynaptic terminals, were preserved in the absence of colony-stimulating factor 1-dependent macrophage activation. As opposed to other Schwann cell-derived cytokines, colony-stimulating factor-1 is expressed by endoneurial fibroblasts, as revealed by in situ hybridization, immunocytochemistry and detection of beta galactosidase expression driven by the colony-stimulating factor-1 promoter. By both light and electron microscopic studies, we detected extended cell-cell contacts between the colony-stimulating factor-1-expressing fibroblasts and endoneurial macrophages as a putative prerequisite for the effective and constant activation of macrophages by fibroblasts in the chronically diseased nerve. Interestingly, in human biopsies from patients with Charcot-Marie-Tooth type 1, we also found frequent cell-cell contacts between macrophages and endoneurial fibroblasts and identified the latter as main source for colony-stimulating factor-1. Therefore, our study provides strong evidence for a similarly pathogenic role of colony-stimulating factor-1 in genetically mediated demyelination in mice and Charcot-Marie-Tooth type 1 disease in humans. Thus, colony-stimulating factor-1 or its cognate receptor are promising target molecules for treating the detrimental, low-grade inflammation of several inherited neuropathies in humans. PMID- 22094539 TI - Clinical significance of the pallidoreticular pathway in patients with carbon monoxide intoxication. AB - Whereas globus pallidus lesions resulting from carbon monoxide intoxication have been extensively described in the literature, the clinical significance of pallidoreticular lesions has rarely been mentioned. This study incorporated information from functional and structural imaging to explore the correlations of pallidoreticular lesions with parkinsonian features and neurobehavioural performance. Twenty-five patients (11 males) with globus pallidus lesions after carbon monoxide intoxication and 25 age- and sex-matched controls were enrolled for detailed neurological examinations, cognitive testing, susceptibility weighted imaging, diffusion tensor imaging and 99mTc-TRODAT-1 single photon emission computed tomography. The post-processing analysis of the neuroimaging included voxel-based morphometry to assess the regional atrophy, tract-based spatial statistics related to white matter involvement, tractography to investigate the rostral and caudal projections from the midbrain level and specific uptake ratios of 99mTc-TRODAT-1 for presynaptic dopaminergic transporter activity. In susceptibility weighted imaging, low-intensity pallidoreticular lesions were detected from the minimal-intensity projections, which were visible in only 7.7% of the T(1)-weighted images and 15.4% of the T(2)-weighted images, whereas inhomogeneous intensities were detected in the globus pallidus. The patients were further divided into two subgroups based on the presence (n = 13) or absence (n = 12) of pallidoreticular lesions. The patients with pallidoreticular lesions showed increased parkinsonian features, poorer performances on the neuropsychiatric tests, lower 99mTc-TRODAT-1 availability in both the caudate and the putamen and greater atrophy of the thalamus, posterior corpus callosum, cerebral peduncle and white matter surrounding the globus pallidus compared to those without pallidoreticular lesions. The tractography results obtained with seed regions of interest in the substantia nigra showed rostral projections to the supplementary motor cortex and anterior cingulate cortex via the globus pallidus; the two pathways were distinct but ran in parallel, caudal to the level of the globus pallidus. In conclusion, the presence of pallidoreticular lesions after carbon monoxide intoxication indicates a poorer cognitive state, which is associated with extensive grey and white matter damage in addition to the damage to the nigra-striatal neuronal networks. The presence of parkinsonian features may be related to pallidal and presynaptic dopaminergic dysfunction. The sensitivity for detecting pallidoreticular lesions can be greatly improved by using susceptibility weighted imaging compared with conventional imaging. PMID- 22094540 TI - A multicenter phase II randomized trial of docetaxel/gemcitabine versus docetaxel/capecitabine as first-line treatment for advanced breast cancer: a Gruppo Oncologico Italia Meridionale study. AB - OBJECTIVE: To evaluate two docetaxel-based regimens as first-line treatment in advanced breast cancer patients. METHODS: Patients were randomly assigned to docetaxel/gemcitabine (arm A: docetaxel 75 mg/m(2) on day 1, gemcitabine 1,000 mg/m(2) on days 1 and 8) or docetaxel/capecitabine (arm B: docetaxel 75 mg/m(2) on day 1, capecitabine 1,250 mg/m(2) twice daily on days 1-14); both chemotherapy regimens were repeated every 21 days. The primary objective of the study was to evaluate the response rate. RESULTS: Seventy-two patients were enrolled (36 each in arms A and B). Responses according to intention-to-treat analysis were as follows: arm A, 41.7% [95% confidence interval (CI) 25.6-57.8]; arm B, 38.9% (95% CI 23-54.8). Median progression-free survival was 10.9 months (95% CI 8.1-13.7) in arm A and 10 months (95% CI 8.8-11.2) in arm B. Overall survival was 26 months (95% CI 22.0-30.0) in arm A and 28 months (95% CI 23.4-32.6) in arm B. Both treatments were well tolerated; myelosuppression was the dose-limiting toxicity, with grade 3-4 neutropenia in 13.8 and 19.4% of the patients in arms A and B, respectively. No relevant differences in other toxicities were observed in the two arms, except for diarrhea (13.9%) and hand-foot syndrome (11.1%), which occurred only in arm B. CONCLUSIONS: Both regimens were active and well tolerated in advanced breast cancer. PMID- 22094541 TI - Evaluation of CD4+/CD8+ T-cell expression and IFN-gamma, perforin secretion for B T constructs of F1 and V antigens of Yersinia pestis. AB - Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Understanding the immune response generated by epitopes recognized by CD4+ and CD8+ T cells is important for the development of safe and effective vaccines designed to promote protective cellular immunity. Apart from humoral response, CD4+ T cells have shown to have a major role in combating the pneumonic form of the disease. In the present study, the secretion of IFN-gamma and IL-4 by splenocytes, stimulated by different constructs of B and T cell epitopes of F1 and V antigens, was measured by ELISpot assay. We also measured perforin and IFN gamma expression as a function of cell mediated immunity by flow cytometry. Three B-T constructs of F1 and seven B-T constructs of V antigens produced a high number of IFN-gamma secreting cells as compared to native antigen and a low number of IL-4 secreting cells. B-T conjugates of F1 and V antigens showed significantly high (p<0.001) percentage of CD4+ IFN-gamma(+) cells as compared to CD8+ IFN-gamma(+) cells. Thus, the study highlights the importance of Th1 cytokine and existence of high proportion of CD4+ T cells probably contributing protection in the host. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response. PMID- 22094542 TI - Molecular properties of lysozyme-microbubbles: towards the protein and nucleic acid delivery. AB - Microbubbles (MBs) have specific acoustic properties that make them useful as contrast agents in ultrasound imaging. The use of the MBs in clinical practice led to the development of more sensitive imaging techniques both in cardiology and radiology. Protein-MBs are typically obtained by dispersing a gas phase in the protein solution and the protein deposited/cross-linked on the gas-liquid interface stabilizes the gas core. Innovative applications of protein-MBs prompt the investigation on the properties of MBs obtained using different proteins that are able to confer them specific properties and functionality. Recently, we have synthesized stable air-filled lysozyme-MBs (LysMBs) using high-intensity ultrasound-induced emulsification of a partly reduced lysozyme in aqueous solutions. The stability of LysMBs suspension allows for post-synthetic modification of MBs surface. In the present work, the protein folded state and the biodegradability property of LysMBs were investigated by limited proteolysis. Moreover, LysMBs were coated and functionalized with a number of biomacromolecules (proteins, polysaccharides, nucleic acids). Remarkably, LysMBs show a high DNA-binding ability and protective effects of the nucleic acids from nucleases and, further, the ability to transform the bacteria cells. These results highlight on the possibility of using LysMBs for delivery of proteins and nucleic acids in prophylactic and therapeutic applications. PMID- 22094543 TI - Non-photochemical laser-induced nucleation of supercooled glacial acetic acid. AB - Non-photochemical laser-induced nucleation (NPLIN) of glacial acetic acid (GAA) is demonstrated. The fraction of samples nucleated depends linearly on peak laser power density at low powers (<100 MW cm(-2)) with a threshold of (9.0 +/- 4.2) MW cm(-2); at higher laser powers the fraction reaches a plateau of 0.75 +/- 0.24 (2sigma uncertainties). A simple model based on polarizability of pre-nucleating clusters gives a value of the solid-liquid interfacial tension gamma(SL) = 15.5 mJ m(-2). It is hoped that the results will stimulate new developments in experimental and theoretical studies of cluster structure and nucleation in liquids. PMID- 22094544 TI - Imitation of drug metabolism in human liver and cytotoxicity assay using a microfluidic device coupled to mass spectrometric detection. AB - In this work, we developed a microfluidic device for the imitation of drug metabolism in human liver and its cytotoxicity on cells. The integrated microfluidic device consists of three sections: (1) bioreactors containing poly(ethylene) glycol (PEG) hydrogel encapsulated human liver microsomes (HLMs); (2) cell culture chambers for cytotoxicity assay; and (3) integrated micro solid phase extraction (SPE) columns to desalt and concentrate the products of enzymatic reaction. To verify the feasibility of the integrated microchip, we studied uridine 5'-diphosphate-glucuronosyltransferase (UGT) metabolism of acetaminophen (AP) and the cytotoxicity of products on HepG2 cells. The products of the reaction in one region of the device were injected into the cell culture chamber for cytotoxicity assay, while those in another region were directly detected online with an electrospray ionization quadrupole time-of-flight mass spectrometer (ESI-Q-TOF MS) after micro-SPE pre-treatment. Semiquantitative analysis achieved in the experiments could be related to the drug-induced HepG2 cell cytotoxicity. Total analysis time for one product was about 30 min and only less than 4 MUg HLM protein was required for one reaction region. The results demonstrated that the established platform could be used to imitate drug metabolism occurring in the human liver, thereby replacing animal experiments in the near future. In addition, the integrated microchip will be a useful tool for drug metabolism studies and cytotoxicity assays, which are pivotal in drug development. PMID- 22094545 TI - Evaluation of the Veterans Health Administration traumatic brain injury screening program in the upper Midwest. AB - OBJECTIVE: To evaluate the Veterans Health Administration's traumatic brain injury (TBI) screening program in terms of predictors of screening and positive screen follow-up. DESIGN: Retrospective administrative data study. Multiple logistic regression analyses were used to estimate the odds of TBI screening at a given appointment and among those screening positive, follow-up in a TBI/polytrauma specialty clinic. PARTICIPANTS: A total of 15,973 Iraq and Afghanistan war veterans treated at a Veterans Affairs medical center in the upper Midwest during the first 18 months of the TBI screening program. RESULTS: Almost 90% of Iraq and Afghanistan veteran patients were offered TBI screening and 17% screened positive. Screening rates increased over time and varied by facility. Appointment type predicted screening with increased likelihood of screening during primary care and TBI/polytrauma clinic appointments. Younger, male, and army veterans without psychiatric diagnoses were more likely to be screened. Fifty-two percent of positive TBI screens had subsequent appointments in a TBI/polytrauma specialty clinic during the study period. Rates of follow-up in the clinic increased over time and varied by facility and patient characteristics. CONCLUSIONS: Within the upper Midwest, Veterans Health Administration has had greater success implementing TBI screening than ensuring follow-up of positive screens in a specialty clinic. Research is needed on barriers to follow-up of positive screens and the outcomes of TBI screening and subsequent specialty care. PMID- 22094546 TI - Can the Glittre ADL test differentiate the functional capacity of COPD patients from that of healthy subjects? AB - BACKGROUND: The Glittre ADL (TGlittre) test is a specifically designed to assess functional limitation in chronic obstructive pulmonary disease (COPD) patients. However, it is not known if it can differentiate the performance of these patients from healthy subjects. OBJECTIVES: To investigate whether the Glittre ADL test is able to differentiate the functional capacity of COPD patients from that of healthy subjects and to compare the cardiorespiratory response between Glittre ADL and the six-minute walk test (6MWT). METHODS: The study included 10 patients with COPD (GOLD 2 to 4) and 10 healthy subjects matched by age who performed the following: spirometry pre- and post-bronchodilator, a Glittre ADL test and two 6MWT on two consecutive days. RESULTS: The performance of COPD (FEV1%pred= 38.1+/-11.8, age=64+/-10 years, BMI=23.7+/-5.2 kg/ m2) was worse than the control group on TGlittre (5.26+/-2.9 min, 3.3+/-0.3 min, p<0.05) and 6MWT (434.97+/-105.18 m vs. 593.25+/-87.36 m, p<0.05). TGlittre correlated with the physical activity domain of the London Chest Activity of Daily Living (LCADL) scale (r=0.67, p<0.05) and with 6MWT when the total sample was analyzed (r=-0.64, p<0.05). The COPD group had a statistically higher (p<0.05) increase in dyspnea (Borg scale) than the control group for both TGlittre and 6MWT, with a similar heart rate and peripheral oxygen saturation variation in both groups (p>0.05). CONCLUSIONS: The performance of COPD patients is worse than that of healthy subjects on the Glittre ADL test, with a greater increase in dyspnea and similar heart rates. PMID- 22094547 TI - Objective structured clinical evaluation as an assessment method for undergraduate chest physical therapy students: a cross-sectional study. AB - BACKGROUND: The Objective Structured Clinical Evaluation (OSCE) has been considered a reliable method for the evaluation of students' clinical skills in health sciences, but it has been rarely applied in the teaching of physical therapy. OBJECTIVE: To assess the use of the OSCE as a tool to evaluate the abilities of undergraduate chest physical therapy students and to verify the internal consistency of the OSCE exam. METHODS: Forty-seven students were evaluated using two types of exams: the traditional exam and the OSCE. Independent educators elaborated the exams. Each question (traditional) or station (OSCE) was given a score ranging from 0.0 to 2.0; being 10.0 the highest possible score of both exams. The relationship between the total score that were obtained from both exams was analyzed using Bland-Altman analysis and Pearson's correlation coefficient. The internal consistency of the OSCE stations was evaluated by four experienced chest physical therapists and it was tested using Cronbach's alpha. RESULTS: The students' average score on the OSCE ranged from 4.4 to 9.6. The internal consistency of the OSCE stations was considered good (0.7). The agreement between exams was analyzed, and it was determined that the exams are not comparable. Examiners also observed a low agreement between the two exams (r=-0.1; p=0.9). CONCLUSION: Our results showed that OSCE and traditional exams are not interchangeable. The OSCE exam had good internal consistency and is able to evaluate aspects that the traditional exam fails to evaluate. PMID- 22094549 TI - Neutrophil activation in severe, early-onset COPD patients versus healthy non smoker subjects in vitro: effects of antioxidant therapy. AB - BACKGROUND: Neutrophils and oxidative stress have been implicated in the pathogenesis of COPD. Severe, early-onset COPD is characterized by a rapid decline in the lung function at an early age; however, nothing is known about neutrophil activation in COPD patients. OBJECTIVES: The aim of this study was to evaluate peripheral blood neutrophil activation in severe, early-onset COPD patients versus healthy non-smokers and the effect of N-acetyl-L-cysteine (NAC) on neutrophil activation in vitro. METHODS: Neutrophils were isolated from 15 severe, early-onset COPD patients and 15 age-matched healthy subjects and stimulated with N-formyl-Met-Leu-Phe (fMLP) in the presence or absence of NAC (10 MUM to 10 mM). Neutrophil chemotaxis, elastase release, reactive oxygen species (ROS), intracellular thiols and apoptosis were measured by Boyden chamber, spectrofluorometry, CMFDA and H2DCF-DA dyes and by annexin V-FITC, respectively. RESULTS: Chemotaxis of peripheral blood neutrophils from COPD patients in response to fMLP was 30% more increased than that observed in healthy subjects. Elastase release in response to fMLP was 2-fold higher in neutrophils from COPD patients versus healthy subjects. Intracellular thiol levels were 30% lower in COPD and ROS was approximately 30% higher in COPD versus healthy neutrophils. Spontaneous apoptosis showed no differences in both groups of patients and fMLP induced apoptosis was higher in COPD. Pre-treatment with the antioxidant NAC effectively attenuated neutrophil chemotaxis, elastase release and ROS as well as effectively increased thiol levels in COPD. CONCLUSIONS: Neutrophils in severe, early-onset COPD patients are highly activated and this is alleviated by NAC in vitro. PMID- 22094550 TI - An instrumented timed up and go: the added value of an accelerometer for identifying fall risk in idiopathic fallers. AB - The Timed Up and Go (TUG) test is a widely used measure of mobility and fall risk among older adults that is typically scored using a stopwatch. We tested the hypothesis that a body-fixed accelerometer can enhance the ability of the TUG to identify community-living older adults with a relatively high fall risk of unknown origin. Twenty-three community-living elderly fallers (76.0 +/- 3.9 years) and 18 healthy controls (68.3 +/- 9.1 years) performed the TUG while wearing a 3D-accelerometer on the lower back. Acceleration-derived parameters included Sit-to-Stand and Stand-to-Sit times, amplitude range (Range), and slopes (Jerk). Average step duration, number of steps, average step length, gait speed, acceleration-median, and standard-deviation were also calculated. While the stopwatch-based TUG duration was not significantly different between the groups, acceleration-derived TUG duration was significantly higher (p = 0.007) among the fallers. Fallers generally exhibited lower Range and Jerk (p < 0.01). While TUG stopwatch duration successfully identified 63% of the subjects, an accelerometer derived three-measure-combination correctly classified 87% of the subjects. Accelerometer-derived measures were generally not correlated with TUG duration. These findings demonstrate that fallers have difficulty with specific TUG aspects that can be quantified using an accelerometer. Without compromising simplicity of testing, an accelerometer can apparently be combined with TUG duration to provide complementary, objective measures that allow for a more complete, sensitive TUG based fall risk assessment. PMID- 22094551 TI - New trends in diagnosis and control strategies for implant infections. AB - In implant infections, a quick and reliable identification of the etiological agent is crucial to realizing efficacious therapies. Among molecular methods, automated ribotyping has proven to be an accurate and rapid technique. More recently, MALDI-TOF/MS and PCR-electrospray ionization (ESI)/MS have been applied successfully to microbiological diagnosis. In implant infections, biofilm is still the major problem for bacterial persistence and recalcitrance to antibiotic therapy. Among biofilm-disrupting agents, enzymes promise the greatest therapeutic possibilities. DNase I degrades biofilm extracellular DNA and has been shown to sensitize biofilm to various biocides and anionic detergents, while dispersin B acts on biofilm exopolysaccharide and, combined with antiseptic, gives a broad-spectrum antibiofilm and antimicrobial activity. The novel antimicrobial approach based on photodynamic treatment (PDT) applies, in combination with antibiotics, to the implant or medical devices reachable by optical fibers. Better progress could be gained by the development of infection resistant biomaterials able to both inhibit bacterial adhesion and promote tissue integration. New knowledge regarding the fibronectin-mediated internalization of Staphylococcus aureus by osteoblasts, and on its role in the pathogenesis of implant-related osteomyelitis, paves the way for the development of vaccines against staphylococcal adhesins, to prevent both adhesion on biomaterials and bacterial invasion of bone cells. PMID- 22094552 TI - Antibiotic-induced biofilm formation. AB - Surface-attached colonies of bacteria known as biofilms play a major role in the pathogenesis of device-related infections. Biofilm colonies are notorious for their resistance to suprainhibitory concentrations of antibiotics. Numerous studies have shown that subminimal inhibitory concentrations of some antibiotics can act as agonists of bacterial biofilm formation in vitro, a process that may have clinical relevance. This article reviews studies demonstrating that low-dose antibiotics induce bacterial biofilm formation. These studies have provided important information about the regulation of biofilm formation and the signaling pathways involved in global gene regulation in response to cell stressors. It is still unclear whether antibiotic-induced biofilm formation contributes to the inconsistent success of antimicrobial therapy for device infections. PMID- 22094554 TI - Influence of Co-Cr particles and Co-Cr ions on the growth of staphylococcal biofilms. AB - PURPOSE: In the last decades, hip prostheses with a metal-on-metal (MOM) bearing have been implanted by orthopedic surgeons worldwide. However, concerns are now raised towards the metal particles and degradation products released by MOM bearings into surrounding tissue, although effects of Co-Cr wear on infection are also unknown. Therefore, we here determine the viable volumes of staphylococcal biofilms formed on polystyrene in the absence and presence of Co-Cr particles and Co-Cr ions. METHODS: Three clinically derived and two commercially available staphylococcal strains were grown in the presence of 2 mg/mL Co-Cr particles or 1000/500 ug/L Co-Cr ions derived from Co-Cr salts or from particle supernatant, under static and dynamic growth conditions. A dynamic model simulates the conditions that apply for biofilm formation in the human body, as synovial fluid in mobile patients with hip prostheses is in constant motion with accompanying shear rates. Images of 24 h old biofilms were made with confocal laser scanning microscopy and analyzed with the mathematical computer program COMSTAT, yielding the biovolume of a biofilm. X-ray photoelectron spectroscopy was performed on the particles to study their elemental surface composition. RESULTS: Most isolates showed a tendency of reduced biofilm growth in the presence of Co-Cr particles compared to growth during exposure to metal ions, but this was only significant in one strain under the dynamic growth condition (Staphylococcus aureus 7388). Characterization of the outer surface of the particles revealed a Co-Cr oxide layer enriched by Mo relative to the bulk concentration. CONCLUSIONS: MOM bearings produce metal particles which were found to possess antibacterial characteristics under dynamic growth conditions. Further research is needed towards the clinical relevance of this finding. PMID- 22094553 TI - Role of antibiofilm-antimicrobial agents in controlling device-related infections. AB - OBJECTIVES: To assess the effects of N-acetylcysteine (NAC) on organism viability in planktonic and biofilm phases, biofilm thickness, and extracellular polysaccharide content. METHODS: We performed time-kill curves and broth macrodilution assays of bacterial and fungal clinical isolates with varying concentrations of NAC. We also created in vitro bacterial biofilms, incubated them with NAC or control, and then stained with propidium iodide and FITC-labeled concanavalin A. We measured biofilm thickness, number of non-viable cells, and fluorescent intensity as a marker of extracellular matrix via a confocal laser scanning microscope. All experiments were conducted in triplicate. Tested organisms included methicillin-sensitive and -resistant Staphylococcus aureus (MSSA, MRSA), S. epidermidis, vancomycin-resistant Enterococcus faecalis (VRE), Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella pneumoniae, Candida albicans and C. krusei. RESULTS: NAC 80 mg/ml was uniformly bactericidal (>99.9% reduction) against all tested bacteria with no recoverable organisms after 30 minutes of incubation, but was fungistatic against candida species. Minimum inhibitory and bactericidal concentrations of NAC ranged from 5-10 mg/ml. Biofilm thickness was significantly decreased in NAC-treated biofilms for all organisms except VRE. The number of non-viable cells in NAC-treated Gram-positive biofilms was increased (p<0.05 for MRSA and VRE). NAC-treated Gram-negative biofilms had scant cellularity and lacked complex 3-dimensional structures that were characteristic of controls. Fluorescent intensity was similar in the experimental and control arms. CONCLUSIONS: NAC is bactericidal against clinically relevant and drug-resistant bacteria and also leads to biofilm disruption. NAC has the potential for use as a novel agent for prevention or treatment of biofilm-related infections. PMID- 22094555 TI - Effect of amphotericin B alone or in combination with rifampicin or clarithromycin against Candida species biofilms. AB - Effectiveness of amphotericin B alone or in combination with rifampicin or clarithromycin on the killing of Candida species biofilms was investigated in vitro. Amphotericin B was assayed at 0.005 to 10 mg/ml. Rifampin and clarithromycin were assayed at 10 mg/ml. We studied 7 Candida albicans, 3 Candida parapsilosis, 3 Candida glabrata, 3 Candida krusei and 2 Candida tropicalis strains. Biofilms were developed in 96-well, flat-bottomed microtiter plates for 48 hours. A synergistic effect between amphotericin B and clarithromycin was demonstrated against 66.6% of C. parapsilosis, 66.6% of C. glabrata, and 42.8% of C. albicans biofilms. A synergistic effect between amphotericin B and rifampin was demonstrated against 66.6% of C. parapsilosis, 42.8% of C. albicans, and 33.3% of C. glabrata biofilms. No synergistic effect was observed against C. krusei or C. tropicalis biofilms with any of the combinations. Rifampin or clarithromycin alone did not exert any effect on Candida species biofilms. Rifampin or clarithromycin combinations with amphotericin B might be of interest in the treatment of Candida biofilm-related infections. PMID- 22094556 TI - Concise survey of Staphylococcus aureus virulence factors that promote adhesion and damage to peri-implant tissues. AB - Staphylococcus aureus is the leading cause of infection in orthopedic implants and of osteomyelitis consequent to it. Here we focus on the wide array of virulence factors that endow S. aureus with its abilities to colonize peri prosthesis tissues and to attack and damage them. Following an infective strategy orchestrated by agr locus, Staphylococcus aureus first deploys virulence factors for adhesion to the prosthesis and peri-prosthesis tissues and then launches its attack by delivering destructive factors. PMID- 22094557 TI - Emerging pathogenetic mechanisms of the implant-related osteomyelitis by Staphylococcus aureus. AB - Implant-related osteomyelitis is a severe and deep infection of bone that arises and develops all around an implant. Staphylococcus aureus is the first cause of osteomyelitis, whether implant-related or not. Bone is an optimal substratum for S. aureus, since this bacterium expresses various adhesins by which can adhere to bone proteins and to the biomaterial surfaces coated with the proteins of the host extracellular matrix. S. aureus is able not only to colonize bone tissues, but also to invade and disrupt them by entering bone cells and inducing cell death and osteolysis. Here we illustrate the pathogenetic mechanisms that can explain how the osteomyelitis sets in and develops around an implant. PMID- 22094558 TI - Internalization by osteoblasts of two Staphylococcus aureus clinical isolates differing in their adhesin gene pattern. AB - Staphylococcus aureus is the leading etiologic agent of implant orthopedic infections. Until recently S. aureus was considered a mere extracellular pathogen; it then turned out to be able to invade eukaryotic cells. Adhesion of S. aureus to peri-prosthesis tissues represents the starting of the infection pathogenesis and the first step of the subsequent internalization of S. aureus by host cells. In the present work the experimental observations on two epidemic clinical strains differing in their adhesin pattern demonstrate the crucial role of the fibronectin-binding protein A in the internalization process and suggest that CNA and Bbp adhesins can play a synergistic role by acting in the initial adhesion of S. aureus to osteoblasts, thus favoring the subsequent FnBPA-mediated internalization. PMID- 22094559 TI - Toll-like receptors (TLRs) in innate immune defense against Staphylococcus aureus. AB - Toll-like receptors (TLRs) are the most important class of innate pattern recognition receptors (PRRs) by which host immune and non-immune cells are able to recognize pathogen-associated molecular patterns (PAMPs). Most mammalian species have 10 to 15 types of TLRs. TLRs are believed to function as homo- or hetero-dimers. TLR2, which plays a crucial role in recognizing PAMPs from Staphylococcus aureus, forms heterodimers with TLR1 or TLR6 and each dimer has a different ligand specificity. Staphylococcal lipoproteins, Panton-Valentine toxin and Phenol Soluble Modulins have been identified as potent TLR2 ligands. Conversely, the ligand function attributed to peptidoglycan and LTA remains controversial. TLR2 uses a MyD88-dependent signaling pathway that results in NF kB translocation into the nucleus and activation of the expression of pro inflammatory cytokine genes. Recognition rouses both an inflammatory response, culminating in the phagocytosis of bacteria, and an adaptive immune response, with the presentation of resulting bacterial compounds to T cells. Here, recent advances on the recognition of S. aureus by TLRs are presented and discussed, as well as the new therapeutic opportunities deriving from this new knowledge. PMID- 22094560 TI - Biofilm growth on implants: bacteria prefer plasma coats. AB - PURPOSE: Bacterial biofilm formation on prostheses or devices used for osteosynthesis is increasingly recognized as cause of persistent infections, an entity known as implant-associated posttraumatic osteomyelitis. Biofilm formation is a very complex, multistep process with adhesion as the first and decisive step. The most prevalent pathogens found are staphylococci species, especially S. aureus, presumably due to a preference to non-biological materials, such as metal. Adherence is influenced by several factors, including the microenvironment, in which blood proteins from serum or plasma might influence adhesion and maybe biofilm formation. The aim of the present study was to test and to compare adherence of S. aureus and P. aeruginosa to different biological and non-biological surfaces in vitro. The question was addressed if coating of the surface by plasma or serum proteins influences bacterial adherence. METHODS: Adherence of radiolabeled bacteria to different surfaces in the presence or absence or serum/plasma proteins was measured over time. RESULTS: When testing adherence of S. aureus to plastic, titanium or to monolayers of epithelial cells (A549) or fibroblasts (Colo800) a clear-cut preference for non-biological surfaces, especially for titanium was seen. Using P. aeruginosa species a similar pattern without a significant difference was revealed. When mimicking the in vivo situation by pre-coating of titanium with human serum or plasma adherence was increased, especially when titanium was coated ("opsonized") by plasma. CONCLUSIONS: Bacterial adherence to surfaces is determined by a variety of factors such as temperature, the presence of nutrients, the absence of host defense systems and the configuration of the covered surface. In vivo, adherence to non-biological surfaces is also influenced by the microenvironment, especially plasma proteins, promoting biofilm formation. PMID- 22094561 TI - Biofilm formation of Candida spp. isolates from patients at a cardiothoracic intensive care unit. AB - Invasive Candida infections in seriously ill patients are rare but associated with high mortality, while Candida colonization of the mucocuteneous surfaces is common in patients admitted to intensive care units. To investigate biofilm formation as a possible virulence factor, we analyzed the biofilm formation of 128 non-invasive isolates from long-term ICU patients and that of 106 invasive bloodstream isolates. Candida biofilms were quantified by the percent transmittance (%Tbloc) method. Crystal Violet (CV) staining was used as marker of biofilm thickness, and XTT assay was used as a marker of the metabolic activity of Candida cells. The ability of biofilm formation was 99.2% in the non-invasive isolates versus 96.2% in the bloodstream isolates (%Tbloc vs.%Tbloc not significant). However, high biofilm production (%Tbloc, >=35) was more frequent among the non-invasive isolates compared to the bloodstream isolates (78.1 vs. 72.5, p<0.001). PMID- 22094562 TI - Extracellular DNA in biofilms. AB - Extracellular DNA (eDNA) is an important biofilm component that was recently discovered. Its presence has been initially observed in biofilms of Pseudomonas aeruginosa, Streptococcus intermedius, Streptococcus mutans, then Enterococcus faecalis and staphylococci. Autolysis is the common mechanism by which eDNA is released. In P. aeruginosa eDNA is generated by lysis of a bacterial subpopulation, under control of quorum sensing system. In E. faecalis autolysis proceeds in a fratricide mode, resulting from a process similar to necrosis of eukaryotic cells. In Staphylococcus aureus autolysis originates by an altruistic suicide, i.e., a programmed cell death similar to apoptosis of eukaryotic cells. In S. aureus autolysis is mediated by murein hydrolase, while in S. epidermidis by the autolysin protein AtlE. In P. aeruginosa eDNA is located primarily in the stalks of mushroom-shaped multicellular structures. In S. aureus the crucial role of eDNA in stabilizing biofilm is highlighted by the disgregating effect of DNase I. eDNA represents an important mechanism for horizontal gene transfer in bacteria. eDNA and other microbial structural motifs are recognized by the innate immune system via the TLR family of pattern recognition receptors (PRRs). PMID- 22094563 TI - Exopolysaccharide production by Staphylococcus epidermidis and its relationship with biofilm extracellular DNA. AB - Implant-related infections are difficult to treat because they are very often associated with biofilm-forming micro-organisms capable of resisting host immune defenses and surviving conventional antibiotic treatments. In Staphylococcus epidermidis biofilm-forming strains, the polysaccharide intercellular adhesin (PIA), whose expression is encoded by the icaADBC operon, is recognized as a main staphylococcal accumulation mechanism. Nevertheless, various observations have shown that PIA expression is dispensable and a variety of additional/alternative accumulation mechanisms, including extracellular DNA (eDNA) and several other factors of proteic nature, can compensate for icaADBC low expression or even for its absence. A suggestive hypothesis points to the possibility that changes in biofilm extracellular matrix composition can be induced in different environmental niches. In this study we aimed at investigating the relationship between the exopolysaccharide and eDNA biofilm components, screening 55 S. epidermidis clinical isolates by means of a simple fluorescence-based microtiter plate assay. Our findings indicate the existence of a certain degree of correlation, although not a strict one, between eDNA and the exopolysaccharide component. The presence of exopolysaccharide greatly varied even in strains belonging to the same strain type determined by automated riboprinting. PMID- 22094564 TI - Biofilm extracellular-DNA in 55 Staphylococcus epidermidis clinical isolates from implant infections. AB - Biofilm formation is broadly recognized as an important virulence factor in many bacterial species implicated in implant-related opportunistic infections. In spite of a long history of research and many investigative efforts aimed at elucidating their chemical composition, structure, and function, the nature of bacterial biofilms still remains only partly revealed. Over the years, different extracellular polymeric substances (EPS) have been described that contribute functionally and structurally to the organization of biofilms. Recently extracellular DNA (eDNA) has emerged as a quantitatively conspicuous and potentially relevant structural component of microbial biofilms of many microbial species, Staphylococcus aureus and S. epidermidis among them. The present study aims at comparatively investigating the amount of eDNA present in the biofilm of 55 clinical isolates of S. epidermidis from postsurgical and biomaterial-related orthopedic infections. Quantification of eDNA was performed by a non-destructive method directly on bacterial biofilms formed under static conditions on the plastic surface of 96-well plates. PMID- 22094565 TI - Molecular diagnostics in periprosthetic joint infection. AB - Periprosthetic joint infection (PJI) is a significant and costly challenge to the orthopedic community. The lack of a gold standard for diagnosis remains the biggest obstacle in the detection and subsequent treatment of PJI. Molecular markers in the serum and joint fluid aspirate hold immense promise to enhance the development of a firm diagnostic criterion. The primary goal is one marker with high sensitivity and specificity. Here, we review our current research efforts in the field of molecular markers: C-reactive protein, erythrocyte sedimentation rate, white blood cells, and leukocyte esterase. Each marker has been studied to determine its sensitivity, specificity, and positive and negative predictive values in diagnosing PJI. PMID- 22094566 TI - Bacterial DNA from orthopedic implants after routine removal. AB - Bacterial 16S rDNA was monitored and identified from orthopedic metallic implants after routine or septic removal from patients in a German hospital. From March to June 2009, 28 metallic implants, 10 human biopsies, and 6 foam dressings from 28 patients were investigated. After analysis of this first collective, the methods were optimized to enhance sensitivity and to reduce interference with human DNA. Then a second collective consisting of 21 metallic implants from 21 patients was investigated from June 2009 to January 2010. In the first collective, 71% of the metallic implants were negative for eubacterial DNA. Pathogens such as Staphylococcus aureus and opportunists such as Lactobacillus rhamnosus were identified in 11% of the samples, whereas the residual 18% positive results were classified as from skin sources or could not be confirmed. Tissue, secretion, and bone samples as well as foam dressings from the same collective also contained pathogens and opportunists. After the optimization of the methods, a considerable increase of positive samples was seen: in the second collective 19 of the 21 metallic implants proved to be positive for eubacterial 16S rDNA. Bacterial DNA from environmental sources was detected in 13 samples, and in 20 specimens, predominantly mostly the skin. Opportunistic pathogens were detected in 19 samples. Interestingly, septic complications did not occur despite the presence of bacterial DNA. The results obtained up to now encourage us not only to continue a directed monitoring of bacterial DNA on orthopedic implants in practice but also to look intensely for possible sources of bacterial contamination during and after insertion or during removal of such implants. PMID- 22094567 TI - Efficacy of debridement in hematogenous and early post-surgical prosthetic joint infections. AB - PURPOSES: To review patients with a hematogenous and early post-surgical prosthetic joint infection (PJI) due to S. aureus treated with debridement and retention of the implant and to compare their clinical characteristics and outcome. METHODS: From January 2000 all patients with a prosthetic joint infection treated in a single-center were prospectively registered and followed up. All potentially variables associated with outcome were recorded. For the present study, cases with a hematogenous or early post-surgical PJI due to S. aureus treated with debridement and at least 2 years of follow-up were reviewed. Cox regression model to identify factors associated with outcome were applied. RESULTS: 12 hematogenous and 53 early post-surgical PJI due to S. aureus were included. Number of patients presenting with fever, leucocyte count, C-reactive protein concentration, and the number of bacteremic patients were significantly higher in hematogenous infections while the number of polymicrobial infections was lower in hematogenous than in early post-surgical infections. The global failure rate in hematogenous and early post-surgical PJI was 58.7% and 24.5%, respectively (p=0.02). The Cox regression model identified hematogenous infections (OR: 2.57, CI95%: 1.02-6.51, p=0.04) and the need of a second debridement (OR: 4.61, CI95%: 1.86-11.4, p=0.001) as independent predictors of failure. CONCLUSION: Hematogenous infections were monomicrobial and had more severe symptoms and signs of infection than early post-surgical PJI. Hematogenous PJI due to S. aureus, using debridement with implant retention, had a worse outcome than early post-surgical infections. PMID- 22094568 TI - Relationship between intraoperative cultures during hip arthroplasty, obesity, and the risk of early prosthetic joint infection: a prospective study of 428 patients. AB - PURPOSE: To evaluate the relationship between intraoperative cultures during hip arthroplasty, the different patient characteristics, and the risk of developing a prosthetic joint infection (PJI). METHODS: A prospective observational study was performed. Patients who underwent elective THA from March 2007 to March of 2011 were included. Three samples were taken just after arthrotomy: synovial fluid inoculated into blood culture flasks (SF), a tissue sample (TS), and a swab of peri- prosthetic tissue (S). Patients received standard antibiotic prophylaxis. The PJI rate within the first 3 months after arthroplasty was recorded. RESULTS: 402 prostheses were included in the study. Contamination rate of synovial fluid was 10.2%. The most frequent isolated microorganism was coagulase-negative staphylococci (CoNS) (32 out of 41). Body mass index (BMI) was the only host characteristic associated with positive intraoperative culture (p=0.009). The PJI rate was 3.7%. Variables associated with PJI in the univariate and multivariate analysis were: age =67 years (p=0.012 OR: 5.35 (1.45-19.81); CI95%) and a BMI =35 (p=0.002, OR: 7.7 (2.12-27.85) CI95%). PJI rate among patients with BMI<35 with negative and positive intraoperative cultures was 3% and 2.7%, respectively, however, the rate among patients with BMI = 35 was 15% and 25%, respectively. CONCLUSION: A BMI =35 was associated with a higher risk of positive intraoperative culture during hip arthroplasty. In addition, a BMI >=35 was independently associated with a high risk of PJI and the highest rate was documented among obese patients with positive intraoperative cultures. PMID- 22094569 TI - Preoperative nutritional status and post-operative infection in total knee replacements: a prospective study of 213 patients. AB - PURPOSE: To assess the potential relationship between preoperative nutritional status, including anthropometric parameters, and infection following total knee replacement surgery. METHODS: A total of 213 patients undergoing total knee replacement between December 2007 and May 2008 were prospectively studied. Patients with rheumatoid arthritis were excluded. For each patient we pre operatively checked biochemical and anthropometric parameters of nutrition information about co-morbidities such as diabetes and high blood pressure, ASA score, age, and gender. Information about early infections, both superficial and deep, was collected. A descriptive statistical analysis and univariate/multivariate logistic regression model for risk factors were performed. RESULTS: Eleven patients (5.16%) had an infection, 5 deep and 6 superficial. Neither co-morbidities nor preoperatively biochemical parameters were associated with infection. However, in the univariate logistic regression model there was an inversely proportional relationship between triceps skinfold (TSF) and infection. After adjusting for age, ASA score and gender (multivariate logistic regression), TSF remained significantly associated with infection. CONCLUSION: There was a statistically significant association between TSF and post-operative infection risk after TKR. LEVEL OF EVIDENCE: Level I (Prospective prognostic study). PMID- 22094570 TI - Copper and silver ion implantation of aluminium oxide-blasted titanium surfaces: proliferative response of osteoblasts and antibacterial effects. AB - Implant infection still represents a major clinical problem in orthopedic surgery. We therefore tested the in vitro biocompatibility and antibacterial effects of copper (Cu)- and silver (Ag)-ion implantation. Discs of a commonly used titanium alloy (Ti6AlV4) with an aluminium oxide-blasted surface were treated by Cu- or Ag-ion implantation with different dosage regimen (ranging from 1e15-17 ions cm(-2) at energies of 2-20 keV). The samples were seeded with primary human osteoblasts and cell attachment and proliferation was analyzed by an MTT-assay. In comparison to the reference titanium alloy there was no difference in the number of attached viable cells after two days. After seven days the number of viable cells was increased for Cu with 1e17 ions cm(-2) at 2 and 5 keV, and for Ag with 1e16 ions cm(-2) at 5 keV while it was reduced for the highest amount of Ag deposition (1e17 ions cm(-2) at 20 keV). Antibacterial effects on S.aureus and E.coli were marginal for the studied dosages of Cu but clearly present for Ag with 1e16 ions cm(-2) at 2 and 5 keV and 1e17 ions cm(-2) at 20 keV. These results indicate that Ag-ion implantation may be a promising methodological approach for antibacterial functionalization of titanium implants. PMID- 22094571 TI - Photoactivated disinfection (PAD) in endodontics: an in vitro microbiological evaluation. AB - PURPOSE: The objective of the present study was the in vitro evaluation by MTT test of the antimicrobial effect of photoactivated disinfection (PAD) and, comparatively, of a conventional 5.25% NaOCl irrigating solution. METHODS: Enterococcus faecalis, Streptococcus mutans and Streptococcus sanguis strains were selected for the test. Freshly extracted single-rooted human teeth were endodontically treated, inoculated with bacterial strains and then divided into different groups, each of them treated with PAD, with PAD plus 0.5% NaOCl solution, with TBO, with PAD for longer time and with 5% NaOCl solution (positive control). RESULTS: The results were significantly different among the various groups, and for Enterococcus faecalis, Streptococcus mutans and Streptococcus sanguis. PAD applied for a longer time (in respect to manufacturer's instructions) or PAD associated to 5% NaOCl showed the significantly higher antibacterial effects. PMID- 22094572 TI - Poly(ethylene glycol) and hydroxy functionalized alkane phosphate self-assembled monolayers reduce bacterial adhesion and support osteoblast proliferation. AB - PURPOSE: Presently there is interest today in designing improved titanium surfaces capable of high bioactivity in order to promote strong anchorage of the bone surrounding implants while at the same time discouraging bioadhesion. Poly(ethylene glycol)-modified (PEG) alkane phosphate and OH-terminated alkane phosphates have been demonstrated to be spontaneously adsorbed onto titanium oxide surfaces and produce surfaces with different protein resistance in relation to the PEG surface density. This study aims to evaluate caries-associated Streptococcus mutans (S. mutans) adhesion and osteoblast proliferation while varying the PEG surface density of titanium surfaces. METHODS: Bacterial adhesion was quantified by fluorescence microscopy and SAOS-2 human osteoblast proliferation was evaluated up to 7 days of culture in vitro. Metabolic activity of osteoblasts was measured by MTT test and the secretion of extracellular matrix proteins (osteopontin, osteocalcin and type I collagen) in culture medium was determined by immunoenzymatic assays. RESULTS: As the PEG surface density increased, the bacterial adhesion considerably decreased when compared to uncoated titanium surfaces. The monomolecular coatings proved to be capable of supporting osteoblast proliferation with the greatest levels of metabolic activity at the highest PEG surface concentrations. CONCLUSIONS: These results are extremely promising for potential clinical application in implant uses where both reduction of bacteria adhesion and stimulation of bone formation are highly desirable. PMID- 22094573 TI - Antibacterial effects of six endodontic sealers. AB - PURPOSE: The objective of this study was to perform an in vitro evaluation of the antibacterial properties of 6 endodontic sealers (Endomethasone C, Argoseal, Bioseal Normal, Acroseal, AH Plus, Sicura Seal). METHODS: The agar diffusion test (well and paper disc methods) with Enterococcus faecalis, Staphylococcus aureus and Streptococcus mutans was used. For the well method, Petri dishes were inoculated with bacterial suspensions. Each well was completely filled with freshly mixed endodontic sealer. For the paper disc method, sterile paper discs were immersed in freshly mixed sealers and put on agar plates. Diameters of halos formed around the sealers were measured after 24 h and 48 h. STATISTICAL ANALYSIS: The effects of well method and of paper disc method were analyzed by 1 way ANOVA. RESULTS: Endomethasone C, Argoseal and Bioseal showed the largest inhibition halos for all the tested microorganisms, while Sicura Seal and AH Plus showed low antibacterial effects. Moreover, the comparison of well method and paper disc methods showed significant statistical differences (P<0,01) for all sealers and indicated a dose-dependent antimicrobial effect. PMID- 22094574 TI - In vitro evaluation of antimicrobial efficacy of endodontic irrigants. AB - PURPOSE: The objective of this study was to compare in vitro, by MTT assay, the antimicrobial efficacy of Niclor 5 (5% NaOCl solution), Cloreximid (0.2% chlorhexidine and 0.2% cetrimide solution), 3% hydrogen peroxide and 17% EDTA against two microorganisms associated with primary endodontic infections. METHODS: Enterococcus faecalis and Streptococcus mutans strains were selected for this test. Freshly extracted single-rooted human teeth were endodontically treated, inoculated with bacterial strains and then divided into different groups, each of them rinsed with Niclor 5 (5% NaOCl solution), Cloreximid (0.2% chlorhexidine and 0.2% cetrimide solution), 3% hydrogen peroxide,17% EDTA and with 5% NaOCl solution (positive control). RESULTS: Even though all the tested irrigating solutions demonstrated antibacterial effects against E. faecalis and S. mutans, the results were significantly different between the various groups. The greatest antimicrobial effects were observed in groups treated with 5% NaOCl and 17% EDTA. Interestingly, the effectiveness of EDTA could be ascribed to its capability of detaching biofilm from canal walls. PMID- 22094575 TI - Bone reconstruction: Au nanocomposite bioglasses with antibacterial properties. AB - Bioglasses are of wide interest since they spontaneously bond and integrate with living bone in the body. By varying the glass chemistry and/or by adding some dopants, it is possible to improve their clinical applications. Gold nanoparticles (Au NPs) are a well-known antibacterial agent, as well as a unique probe for sensing and imaging applications. We report on the synthesis of a 58S bioglass doped with Au NPs at two doping levels: 0.1% wt. and 1% wt. Antibacterial properties were observed on the Gram-positive Staphylococcus aureus, whereas no significant effects were found on the Gram-negative Escherichia coli. A possible mechanism of action of Au NPs towards bacteria has been described. PMID- 22094576 TI - Titanium oxide antibacterial surfaces in biomedical devices. AB - Titanium oxide is a heterogeneous catalyst whose efficient photoinduced activity, related to some of its allotropic forms, paved the way for its widespread technological use. Here, we offer a comparative analysis of the use of titanium oxide as coating for materials in biomedical devices. First, we introduce the photoinduced catalytic mechanisms of TiO2 and their action on biological environment and bacteria. Second, we overview the main physical and chemical technologies for structuring suitable TiO2 coatings on biomedical devices. We then present the approaches for in vitro characterization of these surfaces. Finally, we discuss the main aspects of TiO2 photoactivated antimicrobial activity on medical devices and limitations for these types of applications. PMID- 22094577 TI - Challenges in periprosthetic knee-joint infection. AB - The number of knee arthroplasty procedures is growing and projected to further increase. The risk for periprosthetic joint infection (PJI) is estimated to be low (<1%). However, considering the increasing number of total knee arthroplasty, the increasing number of patients with multiple comorbidities, and the lifelong risk for acquiring hematogenous infection, the total number of PJI will further increase. Despite existing treatment concepts for PJI of the knee, there are still questions to solve, such as type of debridement surgery in case of implant retention, the role of a spacer from a microbiological perspective, and the optimal duration of antimicrobial therapy. In this REVIEW, these questions will be analyzed according to the available literature and the experience of the authors. Moreover, we REVIEW the most recent data on infection, risk factors, and microbiology of PJI. PMID- 22094578 TI - Sensitivity of ring growth and carbon allocation to climatic variation vary within ponderosa pine trees. AB - Most dendrochronological studies focus on cores sampled from standard positions (main stem, breast height), yet vertical gradients in hydraulic constraints and priorities for carbon allocation may contribute to different growth sensitivities with position. Using cores taken from five positions (coarse roots, breast height, base of live crown, mid-crown branch and treetop), we investigated how radial growth sensitivity to climate over the period of 1895-2008 varies by position within 36 large ponderosa pines (Pinus ponderosa Dougl.) in northern Arizona. The climate parameters investigated were Palmer Drought Severity Index, water year and monsoon precipitation, maximum annual temperature, minimum annual temperature and average annual temperature. For each study tree, we generated Pearson correlation coefficients between ring width indices from each position and six climate parameters. We also investigated whether the number of missing rings differed among positions and bole heights. We found that tree density did not significantly influence climatic sensitivity to any of the climate parameters investigated at any of the sample positions. Results from three types of analyses suggest that climatic sensitivity of tree growth varied with position height: (i) correlations of radial growth and climate variables consistently increased with height; (ii) model strength based on Akaike's information criterion increased with height, where treetop growth consistently had the highest sensitivity and coarse roots the lowest sensitivity to each climatic parameter; and (iii) the correlation between bole ring width indices decreased with distance between positions. We speculate that increased sensitivity to climate at higher positions is related to hydraulic limitation because higher positions experience greater xylem tensions due to gravitational effects that render these positions more sensitive to climatic stresses. The low sensitivity of root growth to all climatic variables measured suggests that tree carbon allocation to coarse roots is independent of annual climate variability. The greater number of missing rings in branches highlights the fact that canopy development is a low priority for carbon allocation during poor growing conditions. PMID- 22094579 TI - Trends in skin cancer knowledge, sun protection practices and behaviours in the Northern Ireland population. AB - BACKGROUND: Sun exposure increases risk of skin cancer, especially melanoma, incidence of which continues to rise. Reported skin cancer knowledge and trends in sun care behaviours are documented in a UK region where there has been 20 years of sun-related health promotion campaigns. METHODS: In 2000, 2004 and 2008, a 'care in the sun' module was included in the Northern Ireland (NI) Omnibus survey. Randomly selected subjects were asked to complete a sun-related questionnaire and proportions of respondents analysed by demographic and socio economic factors, with differences tested using z-tests and the chi-squared test. RESULTS: Around 3623 persons responded. Skin cancer knowledge was high (97%). Sun avoidance decreased with time and was lowest among younger age groups and males. Sunscreen use was high (70%), unchanged over 8 years, and more likely among younger age groups, females, those in paid employment, and those with tertiary level education. Use of sunscreen with minimum Sun Protection Factor (SPF) 15 (a campaign message) increased from 45% to 70% (P < 0.01). Skin self-examination was infrequent (8%), less common among those aged >=65 years, males and those with only primary or secondary level education. CONCLUSIONS: Messages on sunscreen use have penetrated the population well, but lower use among the unemployed suggests cost as an issue. Lack of sun avoidance in young people, especially men, poses a risk for further skin cancer increases. Low levels of reported skin self examination in older people, men and those with lower educational attainment identify areas for further action. PMID- 22094580 TI - Alpha-lipoic acid preserves the structural and functional integrity of red blood cells by adjusting the redox disturbance and decreasing O-GlcNAc modifications of antioxidant enzymes and heat shock proteins in diabetic rats. AB - PURPOSE: The aim of this study was to investigate whether the daily administration of alpha-lipoic acid (LA) during 4 weeks prevents the redox disturbance in red blood cells (RBC) described in diabetes METHODS: Multiple low dose streptozotocin (STZ) diabetes was induced in rats by the administration of 40 mg/kg STZ intraperitoneally (i.p.) for 5 consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration. RESULTS: The LA-treated diabetic rats exhibited a general systemic improvement, revealed as the near restoration of body weight and of essential biochemical parameters. The latter was displayed as decreased hyperglycemia, lower triglyceride levels and lower serum activities of alanine aminotransferases and aspartate aminotransferases that point to a general improvement of diabetes-linked organ "lesions". The LA-treated diabetic rats also exhibited significant alleviation of oxidative stress, manifested as decreased lipid peroxidation and lower glycation levels of serum proteins and hemoglobin, while the RBC exhibited increased activities of antioxidant enzymes and elevated levels of reduced glutathione. In RBC, this was accompanied by decreased post translational glycosylation by O-bound beta-N-acetylglucosamine (O-GlcNAc) of the antioxidant enzymes superoxide dismutase and catalase and of heat shock proteins HSP70 and HSP90. CONCLUSION: LA through its powerful antioxidant activity preserves the structural and functional integrity of RBC in diabetes. The RBC can then assume a more efficient role as the first line of systemic defense against diabetic complications arising from oxidative stress-induced damage of other tissues and organs. PMID- 22094581 TI - Soy intake and risk of type 2 diabetes in Chinese Singaporeans [corrected]. AB - PURPOSE: To examine the association between soy products and their components, isoflavones and protein, and incident type 2 diabetes in a population with varied soy intake and high rates of diabetes. METHODS: We used data from the Singapore Chinese Health Study, including 43,176 Chinese men and women aged 45-74 years, free of chronic disease at baseline (1993-1998) and followed through 2004. Intake of individual soy items, total unsweetened soy, and soy components was assessed by food-frequency questionnaire and examined with type 2 diabetes risk using Cox regression. RESULTS: During an average follow-up of 5.7 years, 2,252 of the 43,176 participants included in the current analyses developed diabetes. After adjustment for potential confounders and BMI, consumption of unsweetened soy was inversely associated with diabetes risk. Hazard ratios (HRs) and 95% CI for diabetes across unsweetened soy intake categories (none, 1-4/month, 1-2/week, 3 4/week, >= 5/week) were: 1 (referent), 0.81 (0.67-0.97), 0.76 (0.63-0.91), 0.76 (0.63-0.92), and 0.72 (0.59-0.89), respectively (P (trend) = 0.015). Conversely, in multivariate models, consuming sweetened soybean drink was positively associated with diabetes risk. HRs for diabetes across soybean drink intake categories (none, 1-3/month, 1/week, >= 2/week) were: 1 (referent), 1.07 (0.95 1.20), 1.12 (1.00-1.26), and 1.13 (1.00-1.28), respectively (P (trend) = 0.03). Furthermore, after full adjustment, including adjustment for sweetened soy items, we observed a marginally significant inverse association between isoflavone intake and diabetes (HR for the fifth compared to the first quintile: 0.76; 95% CI: 0.58-1.00; P (trend) = 0.08). CONCLUSIONS: The current findings support a protective role for unsweetened soy foods and isoflavones on risk of type 2 diabetes. PMID- 22094583 TI - Dll1/Notch activation accelerates multiple myeloma disease development by promoting CD138+ MM-cell proliferation. PMID- 22094584 TI - Whole-exome sequencing of pediatric acute lymphoblastic leukemia. AB - Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL. PMID- 22094586 TI - NKL homeobox genes in leukemia. AB - NK-like (NKL) homeobox genes code for transcription factors, which can act as key regulators in fundamental cellular processes. NKL genes have been implicated in divergent types of cancer. In this review, we summarize the involvement of NKL genes in cancer and leukemia in particular. NKL genes can act as tumor-suppressor genes and as oncogenes, depending on tissue type. Aberrant expression of NKL genes is especially common in T-cell acute lymphoblastic leukemia (T-ALL). In T ALL, 8 NKL genes have been reported to be highly expressed in specific T-ALL subgroups, and in ~30% of cases, high expression is caused by chromosomal rearrangement of 1 of 5 NKL genes. Most of these NKL genes are normally not expressed in T-cell development. We hypothesize that the NKL genes might share a similar downstream effect that promotes leukemogenesis, possibly due to mimicking a NKL gene that has a physiological role in early hematopoietic development, such as HHEX. All eight NKL genes posses a conserved Eh1 repressor motif, which has an important role in regulating downstream targets in hematopoiesis and possibly in leukemogenesis as well. Identification of a potential common leukemogenic NKL downstream pathway will provide a promising subject for future studies. PMID- 22094585 TI - Blockade of JAK2-mediated extrinsic survival signals restores sensitivity of CML cells to ABL inhibitors. PMID- 22094587 TI - Silencing of ETV6/RUNX1 abrogates PI3K/AKT/mTOR signaling and impairs reconstitution of leukemia in xenografts. AB - The ETV6/RUNX1 (E/R) gene fusion is generated by the t(12;21) and found in approximately 25% of childhood B-cell precursor acute lymphoblastic leukemia. In contrast to the overwhelming evidence that E/R is critical for the initiation of leukemia, its relevance for the maintenance of overt disease is less clear. To investigate this issue, we suppressed the endogenous E/R fusion protein with lentivirally transduced short hairpin RNA in the leukemia cell lines REH and AT 2, and found a distinct reduction of proliferation and cell survival. In line with the observed concurrent inactivation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, pharmacological inhibition diminished the phosphorylation of AKT and ribosomal protein S6, and significantly increased the apoptosis rate in E/R-positive leukemias. Moreover, PI3K/mTOR inhibitors sensitized glucocorticoid-resistant REH cells to prednisolone, an observation of potential relevance for improving treatment of drug-resistant relapses. Of note, knockdown of the E/R fusion gene also severely impaired the repopulation capacity of REH cells in non-obese deficient/severe combined immunodeficient mice. Collectively, these data demonstrate that the E/R fusion protein activates the PI3K/AKT/mTOR pathway and is indispensible for disease maintenance. Importantly, these results provide a first rationale and justification for targeting the fusion gene and the PI3K/AKT/mTOR pathway therapeutically. PMID- 22094588 TI - Toward relational empowerment. AB - Psychological empowerment has been theorized as a construct with emotional, behavioral and cognitive components. Yet, many studies have stressed that empowerment processes are contingent on interpersonal relationships. Moreover, theory suggests that power is developed and exercised through relationships. This article makes the case that expanding our conceptions of psychological empowerment through the addition of a relational component can enhance our understanding of psychological empowerment and the effectiveness of empowerment oriented community practice. Previous research on empowerment is reviewed for relational content, and additional insights into the relational context of empowerment processes are marshaled from other concepts in community research including social capital, sense of community, social networks, social support, and citizen participation. A new iteration of the nomological network for psychological empowerment is presented, including the elements of a relational component. PMID- 22094589 TI - Two C-type lectins from shrimp Litopenaeus vannamei that might be involved in immune response against bacteria and virus. AB - C-type lectins play crucial roles in innate immunity to recognize and eliminate pathogens efficiently. In the present study, two C-type lectins from shrimp Litopenaeus vannamei (designated as LvLectin-1 and LvLectin-2) were identified, and their expression patterns, both in tissues and toward pathogen stimulation, were then characterized. The full-length cDNA of LvLectin-1 and LvLectin-2 was 567 and 625 bp, containing an open reading frame (ORF) of 471 and 489 bp, respectively, and deduced amino acid sequences showed high similarity to other members of C-type lectin superfamily. Both two C-type lectins encoded a single carbohydrate-recognition domain (CRD). The motif of Ca(2+) binding site 2 in CRD, which determined carbohydrate-binding specificity, was QPN (Gln(122)-Pro(123) Asn(124)) in LvLectin-1, but QPD (Gln(128)-Pro(129)-Asp(130)) in LvLectin-2. Two C-type lectins exhibited similar tissue expression pattern, for their mRNA were both constitutively expressed in all tested tissues, including hepatopancreas, muscle, gill, hemocytes, gonad and heart, furthermore they were both mostly expressed in hepatopancreas, though the expression level of LvLectin-2 was much higher than LvLectin-1. The expression level of two C-type lectins mRNA in hemocytes varied greatly after the challenge of Listonella anguillarum or WSSV. After L. anguillarum challenge, the expression of both C-type lectins were significantly (P<0.01) up-regulated compared with blank group, and LvLectin-1 exhibited higher level than LvLectin-2; while after the stimulation of WSSV, the expression of LvLectin-2 was significantly up-regulated at 6 h (P<0.01) and 12 h (P<0.05), but the expression level of LvLectin-1 down-regulated significantly (P<0.01) to 0.4-fold at 6 and 12 h post-stimulation. The results indicated that the two C-type lectins might be involved in immune response toward pathogen infection, and they might perform different recognition specificity toward bacteria or virus. PMID- 22094590 TI - Spectroscopic methods in gas hydrate research. AB - Gas hydrates are crystalline structures comprising a guest molecule surrounded by a water cage, and are particularly relevant due to their natural occurrence in the deep sea and in permafrost areas. Low molecular weight molecules such as methane and carbon dioxide can be sequestered into that cage at suitable temperatures and pressures, facilitating the transition to the solid phase. While the composition and structure of gas hydrates appear to be well understood, their formation and dissociation mechanisms, along with the dynamics and kinetics associated with those processes, remain ambiguous. In order to take advantage of gas hydrates as an energy resource (e.g., methane hydrate), as a sequestration matrix in (for example) CO(2) storage, or for chemical energy conservation/storage, a more detailed molecular level understanding of their formation and dissociation processes, as well as the chemical, physical, and biological parameters that affect these processes, is required. Spectroscopic techniques appear to be most suitable for analyzing the structures of gas hydrates (sometimes in situ), thus providing access to such information across the electromagnetic spectrum. A variety of spectroscopic methods are currently used in gas hydrate research to determine the composition, structure, cage occupancy, guest molecule position, and binding/formation/dissociation mechanisms of the hydrate. To date, the most commonly applied techniques are Raman spectroscopy and solid-state nuclear magnetic resonance (NMR) spectroscopy. Diffraction methods such as neutron and X-ray diffraction are used to determine gas hydrate structures, and to study lattice expansions. Furthermore, UV-vis spectroscopic techniques and scanning electron microscopy (SEM) have assisted in structural studies of gas hydrates. Most recently, waveguide-coupled mid-infrared spectroscopy in the 3-20 MUm spectral range has demonstrated its value for in situ studies on the formation and dissociation of gas hydrates. This comprehensive review summarizes the importance of spectroscopic analytical techniques to our understanding of the structure and dynamics of gas hydrate systems, and highlights selected examples that illustrate the utility of these individual methods. PMID- 22094591 TI - Simultaneous quantification of methylated purines in DNA by isotope dilution LC MS/MS coupled with automated solid-phase extraction. AB - Since methylation at the N-7 and O(6) positions of guanine and the N-3 position of adenine in DNA are the predominant reaction sites, N(7)-methylguanine (N(7) MeG), O(6)-methylguanine (O(6)-MeG), and N(3)-methyladenine (N(3)-MeA) have been suggested as good biomarkers for assessing exposure to methylating agents. Here, we report the development of a sensitive and selective assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) to simultaneously measure N(7) MeG, O(6)-MeG, and N(3)-MeA in DNA hydrolysates. With the use of isotope internal standards ((15)N(5)-N(7)-MeG, d(3)-O(6)-MeG, and d(3)-N(3)-MeA) and online solid phase extraction, DNA hydrolysates can be directly analyzed within 12 min without prior sample purification. The limits of detection were 0.02, 0.002, and 0.01 ng/mL on-column (6.1, 0.6, and 3.4 fmol) for N(7)-MeG, O(6)-MeG, and N(3)-MeA, respectively. Inter- and intraday imprecision (CV) were 3.6-9.6% and 2.7-13.6%, respectively. Mean recoveries were 96-109%. This method was then applied to quantitate the amounts of methylated purines in calf thymus DNA treated with methyl methanesulfonate (MMS). The levels of N(7)-MeG, O(6)-MeG, and N(3)-MeA in calf thymus DNA increase with MMS concentration and incubation time. The ratio of relative yields of N(7)-MeG, O(6)-MeG, and N(3)-MeA in MMS-treated DNA was found to be 1.00:0.0032:0.119, respectively. This LC-MS/MS assay provides the sensitivity and high throughput required to evaluate the extent of methylated lesions in DNA induced by methylating agents. PMID- 22094592 TI - New mothers and media use: associations between blogging, social networking, and maternal well-being. AB - Drawing on Bronfenbrenner's ecological theory and prior empirical research, the current study examines the way that blogging and social networking may impact feelings of connection and social support, which in turn could impact maternal well-being (e.g., marital functioning, parenting stress, and depression). One hundred and fifty-seven new mothers reported on their media use and various well being variables. On average, mothers were 27 years old (SD = 5.15) and infants were 7.90 months old (SD = 5.21). All mothers had access to the Internet in their home. New mothers spent approximately 3 hours on the computer each day, with most of this time spent on the Internet. Findings suggested that frequency of blogging predicted feelings of connection to extended family and friends which then predicted perceptions of social support. This in turn predicted maternal well being, as measured by marital satisfaction, couple conflict, parenting stress, and depression. In sum, blogging may improve new mothers' well-being, as they feel more connected to the world outside their home through the Internet. PMID- 22094593 TI - Early work patterns for gynaecological cancer survivors in the USA. AB - BACKGROUND: Little is known about the balance between work demands and treatment plans for >4.3 million working-age cancer survivors in the USA. AIMS: To describe changes in work status for gynaecological cancer survivors during the first 6 months following diagnosis and their experience with their employers' programmes and policies. METHODS: One hundred and ten gynaecological cancer survivors who were working at the time of their cancer diagnosis completed a survey. Case record reviews documented their clinical characteristics and treatment details. RESULTS: Ninety-five women (86%) had surgery; 81 (74%) received chemotherapy, radiotherapy or both in addition to surgery. Nine per cent of women said that they changed their treatment plan because of their jobs; in contrast, 62% of women said that they changed their work situation to accommodate their treatment plan. Overall, the most common month for women to stop working was Month 1 (41%), to decrease hours was Month 2 (32%) and to increase hours was Month 6 (8%). Twenty-eight per cent of women were aware of employer policies that assisted the return to work process; 70% of women were familiar with the Family and Medical Leave Act (FMLA) and 56% with the Americans with Disabilities Act (ADA). Only 26% completed a formal request for work accommodations. After 6 months, 56 of 83 women (67%) remained working or had returned to work. CONCLUSIONS: Work patterns varied for these gynaecological cancer survivors over the first 6 months following diagnosis. Opportunities exist to improve communication about work and treatment expectations between cancer survivors, occupational health professionals, employers and treating clinicians. PMID- 22094595 TI - Clinical and cellular consequences of the mutation m.12300G>A in the mitochondrial tRNA(Leu(CUN)) gene. AB - We report, for the first time, a patient with an overlap MERRF-NARP syndrome who carries the mutation m.12300G>A in the mitochondrial tRNA(Leu(CUN)) gene. The mutation was heteroplamic and more abundant in her muscle and fibroblast than in blood from her oligosymptomatic mother. Single muscle fiber analysis revealed that the proportion of mutant mtDNA in ragged red fibers was higher than that in normal fibers. Combined defects of mitochondrial respiratory chain complexes were detected in muscle, fibroblasts and transmitochondrial hybrid cells. Significant reduction of total ATP and mitochondrial membrane potential and an increased production of reactive oxygen species were observed. PMID- 22094594 TI - A retrospective comparison of docetaxel and paclitaxel for patients with advanced or recurrent esophageal cancer who previously received platinum-based chemotherapy. AB - OBJECTIVE: To retrospectively compare docetaxel (DTX) with paclitaxel (PTX) with regard to efficacy and safety in advanced or recurrent esophageal cancer patients who previously received platinum-based chemotherapy. METHODS: We retrospectively analyzed 124 advanced or recurrent esophageal cancer patients who had received platinum-based chemotherapy and then received DTX or PTX from April 2006 to November 2010. RESULTS: Eighty-six patients (69.4%) received DTX and 38 patients (30.6%) received PTX monotherapy. Due to toxicity, dose reduction was needed in 36.0 and 27.8% of patients and treatment was discontinued in 10.5 and 2.6% of patients receiving DTX and PTX, respectively. The objective response (25.7 vs. 10.3%, p = 0.03) and disease control rates (60.0 vs. 34.6%, p = 0.01) were higher in the PTX group than in the DTX group, respectively. There were no significant differences in median progression-free survival (2.1 vs. 3.5 months) and overall survival (6.1 vs. 7.2 months) between the DTX and PTX groups, respectively. Grade 3-4 neutropenia (48.8 vs. 21.1%, p = 0.003) and febrile neutropenia (20.9 vs. 5.3%, p = 0.029) were more frequent in the DTX patients than in the PTX patients, respectively. CONCLUSION: Although the efficacy of DTX and PTX for advanced or recurrent esophageal cancer patients after platinum-based chemotherapy was not significantly different in terms of survival, PTX was a more feasible treatment. PTX provided similar efficacy to DTX with less febrile neutropenia. PMID- 22094596 TI - Validation of the portuguese version of the antisocial process screening device self-report with a focus on delinquent behavior and behavior problems. AB - The main objectives of the present study were to validate a Portuguese version of the Antisocial Process Screening Device-Self-Report and to evaluate the predictive importance of some constructs in discriminating between inmate delinquent youth and community youth. With a total of 760 participants, male (n = 543) and female (n = 217), divided in an inmate forensic sample (n = 250) and a community sample (n = 510), the authors were able to demonstrate psychometric properties that justify its use with the Portuguese juvenile population, in terms of factor structure, internal consistency, temporal stability, convergent validity, divergent validity, concurrent validity, and cutoff score. The predictive importance of psychopathic traits, self-reported delinquent behavior, and behavior problems on the prediction of sample membership (forensic vs. community) was established by binary logistic regression. PMID- 22094597 TI - Informal social support among returning young offenders: a metasynthesis of the literature. AB - Informal social support has long been touted as a key to success for young offenders, but little empirical work has concretized these benefits. This article explores the dynamics of informal social support for returning young offenders (ages 14-24), particularly in the context of peers and family members. The authors use a metasynthesis methodology to examine 13 qualitative articles and dissertations published in the United States from 1998 through 2010. Analysis of these texts found two major themes related to informal support from peers and family members. Young offenders "walked a fine line" with their peers, who provided not only a sense of belonging and possibly a route to material assistance but also temptations and opportunities to reengage with criminal activity. Family members provided the supports and comforts of "the ties that bind" but with potentially unrealistic expectations and reenactment of old roles and negative dynamics. Through this metasynthesis, the authors forge an understanding of informal social support that complicates its presumed benefits for the reentry of young offenders. PMID- 22094598 TI - The practice of positive criminology: a Vipassana course in prison. AB - Positive criminology is a new term for a perspective associated with theories and models that relate to socially inclusive, positively experienced influences that assist individuals in desisting or refraining from criminal and deviant behavior. A qualitative phenomenological study of prisoners who were in recovery from substance dependency and who participated in a Vipassana course in a rehabilitative prison introduces features of positive criminology. A total of 22 male prisoners participated in a 10-day Vipassana course run by volunteers in prison. Deep interviews were conducted with participants before, immediately after, and 3 to 4 months after the course. The findings describe components of positive criminology that had meaningful impact on the prisoners in rehabilitation: perceived goodness, positive relationship with the prison staff, positive social atmosphere, and overcoming an ordeal. Implications for practice and further research are outlined. PMID- 22094599 TI - Evaluating the relation between psychopathy and affective empathy: two preliminary studies. AB - It is widely believed that impairment in an ability to experience affective empathy for others is a central feature of psychopathy. The authors tested this assumption by covertly manipulating and measuring state experiences of emotional contagion and empathic concern in college undergraduates and male forensic inpatients. Surprisingly, they found little evidence of a negative association between psychopathy and affective empathy in either sample. In those instances in which associations were found, they tended to indicate that higher psychopathy was associated with increased affective empathy. Follow-up analyses also revealed that psychopathy was positively associated with pervasive experiences of sadness, anger, and fear, and negatively associated with pervasive experiences of happiness among nonforensic individuals. This research raises questions about existing conceptualizations of interpersonal affect in psychopathy and offers suggestions for advancing future understanding of the role-played by emotional processes in psychopathy. PMID- 22094600 TI - Metabolic development in the liver and the implications of the n-3 fatty acid supply. AB - The n-3 fatty acids contribute to regulation of hepatic fatty acid oxidation and synthesis in adults and accumulate in fetal and infant liver in variable amounts depending on the maternal diet fat composition. Using 2D gel proteomics and matrix-assisted laser desorption/ionization time of flight mass spectrometry, we recently identified altered abundance of proteins associated with glucose and amino acid metabolism in neonatal rat liver with increased n-3 fatty acids. Here, we extend studies on n-3 fatty acids in hepatic metabolic development to targeted gene and metabolite analyses and map the results into metabolic pathways to consider the role of n-3 fatty acids in glucose, fatty acid, and amino metabolism. Feeding rats 1.5% compared with <0.1% energy 18:3n-3 during gestation led to higher 20:5n-3 and 22:6n-3 in 3-day-old offspring liver, higher serine hydroxymethyltransferase, carnitine palmitoyl transferase, and acyl CoA oxidase and lower pyruvate kinase and stearoyl CoA desaturase gene expression, with higher cholesterol, NADPH and glutathione, and lower glycine (P < 0.05). Integration of the results suggests that the n-3 fatty acids may be important in facilitating hepatic metabolic adaptation from in utero nutrition to the postnatal high-fat milk diet, by increasing fatty acid oxidation and directing glucose and amino acids to anabolic pathways. PMID- 22094602 TI - Current and emerging approaches to define intestinal epithelium-specific transcriptional networks. AB - Upon developmental or environmental cues, the composition of transcription factors in a transcriptional regulatory network is deeply implicated in controlling the signature of the gene expression and thereby specifies the cell or tissue type. Novel methods including ChIP-chip and ChIP-Seq have been applied to analyze known transcription factors and their interacting regulatory DNA elements in the intestine. The intestine is an example of a dynamic tissue where stem cells in the crypt proliferate and undergo a differentiation process toward the villus. During this differentiation process, specific regulatory networks of transcription factors are activated to target specific genes, which determine the intestinal cell fate. The expanding genomewide mapping of transcription factor binding sites and construction of transcriptional regulatory networks provide new insight into how intestinal differentiation occurs. This review summarizes the current overview of the transcriptional regulatory networks driving epithelial differentiation in adult intestine. The novel technologies that have been implied to study these networks are presented and their prospects for implications in future research are also addressed. PMID- 22094601 TI - Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation. AB - Steatotic livers are sensitive to ischemic events and associated ATP depletion. Hepatocellular necrosis following these events may result from mitochondrial uncoupling protein-2 (UCP2) expression. To test this hypothesis, we developed a model of in vitro steatosis using primary hepatocytes from wild-type (WT) and UCP2 knockout (KO) mice and subjected them to hypoxia/reoxygenation (H/R). Using cultured hepatocytes treated with emulsified fatty acids for 24 h, generating a steatotic phenotype (i.e., microvesicular and broad-spectrum fatty acid accumulation), we found that the phenotype of the WT and UCP2 KO were the same; however, cellular viability was increased in the steatotic KO hepatocytes following 4 h of hypoxia and 24 h of reoxygenation; Hepatocellular ATP levels decreased during hypoxia and recovered after reoxygenation in the control and UCP2 KO steatotic hepatocytes but not in the WT steatotic hepatocytes; mitochondrial membrane potential in WT and UCP2 KO steatotic groups was less than control groups but higher than UCP2 KO hepatocytes. Following reoxygenation, lipid peroxidation, as measured by thiobarbituric acid reactive substances, increased in all groups but to a greater extent in the steatotic hepatocytes, regardless of UCP2 expression. These results demonstrate that UCP2 sensitizes steatotic hepatocytes to H/R through mitochondrial depolarization and ATP depletion but not lipid peroxidation. PMID- 22094603 TI - Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs. AB - Total parenteral nutrition (TPN) is essential for patients with impaired gut function but leads to parenteral nutrition-associated liver disease (PNALD). TPN disrupts the normal enterohepatic circulation of bile acids, and we hypothesized that it would decrease intestinal expression of the newly described metabolic hormone fibroblast growth factor-19 (FGF19) and also glucagon-like peptides-1 and -2 (GLP-1 and GLP-2). We tested the effects of restoring bile acids by treating a neonatal piglet PNALD model with chenodeoxycholic acid (CDCA). Neonatal pigs received enteral feeding (EN), TPN, or TPN + CDCA for 14 days, and responses were assessed by serum markers, histology, and levels of key regulatory peptides. Cholestasis and steatosis were demonstrated in the TPN group relative to EN controls by elevated levels of serum total and direct bilirubin and also bile acids and liver triglyceride (TG) content. CDCA treatment improved direct bilirubin levels by almost fourfold compared with the TPN group and also normalized serum bile acids and liver TG. FGF19, GLP-1, and GLP-2 were decreased in plasma of the TPN group compared with the EN group but were all induced by CDCA treatment. Intestinal mucosal growth marked by weight and villus/crypt ratio was significantly reduced in the TPN group compared with the EN group, and CDCA treatment increased both parameters. These results suggest that decreased circulating FGF19 during TPN may contribute to PNALD. Moreover, we show that enteral CDCA not only resolves PNALD but acts as a potent intestinal trophic agent and secretagogue for GLP-2. PMID- 22094604 TI - Pelvic support osteotomy for unstable hips using hybrid external fixator: case series and review of literature. AB - BACKGROUND: Instability of the hip joint is a source of great discomfort to the patient due to pain, limp and leg-length discrepancy. Pelvic support osteotomy with Ilizarov hip reconstruction, along with its various modifications, has emerged as a standard treatment modality for this difficult problem. We present a series of patients with unstable hips treated with a modification of the monolateral fixator-the hybrid external fixator. MATERIALS AND METHODS: A retrospective review of a series of 23 patients (38 hips) with unstable hips treated at our institute with the hybrid external fixator was performed. The mean age of the patients was 19.1 years (range 7-49 years). The outcomes were evaluated radiologically and clinically using the Harris hip score. RESULTS: After a mean follow-up period of 30.5 months (range 10-91 months), the range of motion of the hip had improved, pain had decreased, and the Harris hip score had improved from 63.43 to 75.17, which was statistically significant. The pre operative knee range of motion was achieved in all patients by the last follow up. Trendelenburg gait disappeared in all patients except for 3, limb length discrepancy improved from a pre-operative mean of 43 mm to a post-operative mean of 5 mm at final follow-up, and the mechanical axis was regained in all patients. Pin-tract infections were the commonest complications, occurring in 12 patients (52%). CONCLUSIONS: This study shows that pelvic support osteotomy using the new hybrid external fixator, which combines the versatility and modularity of the Ilizarov frame with the compactness of the monolateral fixator, is a useful treatment modality in individuals with unstable hips. PMID- 22094605 TI - Use of cementless acetabular component with a hook and iliac flanges in revision arthroplasty for massive acetabular defect. AB - BACKGROUND: Revision hip arthroplasty of massive acetabular defect, severe combined defect, or pelvic discontinuity is challenging. The purpose of this study was to determine the midterm outcome and survivorship of a new revision technique using cementless acetabular cup supplemented with a hook and three iliac flanges in massive acetabular defects. MATERIALS: From January 2000 to June 2004, we revised 17 severe acetabular defects, 14 combined defects and three pelvic discontinuities according to the American Academy of Orthopaedic Surgeons (AAOS) classifications, in which bone stock at the dome was not available to provide support for the cup. These revisions were performed using a cementless porous-coated hemispherical cup with a hook and flanges. RESULTS: One patient (one hip) underwent resection arthroplasty due to infection 1 year after the revision. The remaining 16 hips were evaluated at a mean of 6.8 (range 5-9) years postoperatively. Thirteen acetabular components (81%) showed no migration and were stable with bone ingrowth. Three hips showed progressive medial and upward migration during the 18-24 months after the index revision, after which migration was not progressive. The Merle d'Aubigne hip score was 14.5 (range 12-18) points at the latest follow-up evaluation. Survival rate was 94.4% when revision for any reason was considered as the end point [95% confidence interval (CI) 83.9-100%] and 82.0% (95% CI 62.8-100%) when loosening of the cup was considered as the end point. CONCLUSION: Results of this type of revision were superior to previously reported results of acetabular revisions with the use of various techniques and devices. PMID- 22094606 TI - Changes in pennation angle in rotator cuff muscles with torn tendons. AB - BACKGROUND: Although several authors have reported on the pennation angles of intact rotator cuff muscles, the relationship between their alteration and rotator cuff tears has not been fully clarified. The purpose of this study was to measure the pennation angles of human cadaveric rotator cuff muscles with torn tendons. METHODS: Twenty embalmed cadaveric shoulders were studied. Ten shoulders with various types of rotator cuff tears (tear group) were compared with ten shoulders that had intact rotator cuff tendons (control group). In seven shoulders with full-thickness tears, the area of the tear was determined by multiplying its length and width. After removing the muscles from the scapula, the superficial muscle fibers of each muscle were removed layer by layer until the entire intramuscular tendon was exposed. Photographs were taken and the pennation angles were then measured on digital images. The correlation between the size of the tear and the pennation angles of the supraspinatus and the infraspinatus muscles were determined statistically. RESULTS: The pennation angles of the supraspinatus and infraspinatus muscles in the tear group were significantly greater than those in the control group (P = 0.027 and 0.007, respectively). In seven shoulders with full-thickness rotator cuff tears, a positive correlation was found between the pennation angle of the supraspinatus muscle and the tear length (r = 0.854, P = 0.014). Moreover, a positive correlation was found between the pennation angle of the infraspinatus muscle and the tear area (r = 0.759, P = 0.048). On the other hand, the pennation angle was not affected by the presence of the partial-thickness tears in the remaining three shoulders. DISCUSSION AND CONCLUSION: In rotator cuff tears, the pennation angles of the involved rotator cuff muscles increased with increasing size of the tear. PMID- 22094607 TI - Characteristics of neck and shoulder pain (called katakori in Japanese) among members of the nursing staff. AB - BACKGROUND: The characteristics of neck and shoulder pain (NSP), called katakori in Japanese, have not been well documented to date. The aim of this study was to clarify the characteristics of NSP through a questionnaire survey of members of the nursing staff. METHODS: The study population consisted of 484 nursing staff members of Gunma University Hospital in Japan. The questionnaire involved information on age, body mass index (BMI), gender, psychological stress at work, musculoskeletal pain at other anatomic sites (elbow/wrist, lumbar and knee), smoking history, and hypertension. If subjects had NSP, they were asked about any coexisting symptoms, the utilization of health services, and the precise location of NSP. RESULTS: The total study population included 393 persons after 91 persons were excluded for various reasons. The point prevalence of NSP was 68.1% (268 of 393). Age, BMI, smoking history, and hypertension showed no significant trend for the prevalence of NSP in the univariate analyses. The occurrence of NSP was significantly higher in subjects with psychological stress, elbow/wrist pain, lumbar pain, and knee pain, respectively. A multivariate logistic regression analysis showed that gender, psychological stress, elbow/wrist pain, and lumbar pain were significantly associated with the occurrence of NSP. One hundred fifty eight of those with NSP (58.9%) reported coexisting symptoms, and the most common was headache. Fifty-seven (21.2%) of the subjects with NSP had consulted medical or health practitioners, and bone setting was the most common service provider. The most common area of NSP was the superior part of the trapezius. CONCLUSIONS: This study confirmed that NSP, katakori in Japanese, is a prevalent problem in a nursing staff, and several factors associated with NSP were identified. PMID- 22094608 TI - Formation of Pt-TiO2-rGO 3-phase junctions with significantly enhanced electro activity for methanol oxidation. AB - TiO(2) nanoparticles-decorated graphene nanosheets have been prepared by a facile hydrothermal method. After depositing Pt nanoparticles exclusively around the interface between TiO(2) and rGO, the obtained Pt/TiO(2)@rGO electrocatalyst exhibits remarkably enhanced electrocatalytic performance, which could be attributed to the unique structure and some possible synergetic effect from the 3 phase Pt-TiO(2)-rGO junctions. PMID- 22094609 TI - Integrated separation of blood plasma from whole blood for microfluidic paper based analytical devices. AB - Many diagnostic tests in a conventional clinical laboratory are performed on blood plasma because changes in its composition often reflect the current status of pathological processes throughout the body. Recently, a significant research effort has been invested into the development of microfluidic paper-based analytical devices (MUPADs) implementing these conventional laboratory tests for point-of-care diagnostics in resource-limited settings. This paper describes the use of red blood cell (RBC) agglutination for separating plasma from finger-prick volumes of whole blood directly in paper, and demonstrates the utility of this approach by integrating plasma separation and a colorimetric assay in a single MUPAD. The MUPAD was fabricated by printing its pattern onto chromatography paper with a solid ink (wax) printer and melting the ink to create hydrophobic barriers spanning through the entire thickness of the paper substrate. The MUPAD was functionalized by spotting agglutinating antibodies onto the plasma separation zone in the center and the reagents of the colorimetric assay onto the test readout zones on the periphery of the device. To operate the MUPAD, a drop of whole blood was placed directly onto the plasma separation zone of the device. RBCs in the whole blood sample agglutinated and remained in the central zone, while separated plasma wicked through the paper substrate into the test readout zones where analyte in plasma reacted with the reagents of the colorimetric assay to produce a visible color change. The color change was digitized with a portable scanner and converted to concentration values using a calibration curve. The purity and yield of separated plasma was sufficient for successful operation of the MUPAD. This approach to plasma separation based on RBC agglutination will be particularly useful for designing fully integrated MUPADs operating directly on small samples of whole blood. PMID- 22094610 TI - Brainstorming for breakthrough thinking. AB - This department highlights change management strategies that may be used in strategically planning and executing organizational change initiatives. With the goal of presenting practical approaches helpful to nurse leaders advancing organizational change, content includes evidence-based projects, tools, and resources that mobilize and sustain organizational change initiatives. In this article, the author discusses brainstorming as a viable innovation technique and goal-based change intervention. PMID- 22094611 TI - Transformational leadership. AB - This month, the director of the Magnet Recognition Program(r) takes an in-depth look at the Magnet(r) model component transformational leadership. The author examines the expectations for Magnet organizations around this component. What are the qualities that make a nursing leader truly transformational, and what is the best approach to successfully lead a healthcare organization through today's volatile healthcare environment? PMID- 22094612 TI - Patient-centered healthcare design. AB - Patient-centered care focuses on the patient's and family's experience in the hospital, and the design of the healthcare environment should support the patient centered care concept. The purpose of this facility design department is to expand nurse leaders' knowledge and competencies in health facility design and enable them to take leadership roles in design efforts. This article focuses on healthcare design guiding principles and features to support organizational cultural initiatives such as patient- and family-centered care and Planetree. PMID- 22094613 TI - Clinical intelligence. AB - Clinical intelligence is an emerging field in healthcare that will change nursing practice, driving clinical outcomes and operational efficiencies. Clinical intelligence is essential to healthcare organizations in fully realizing the value of the growing amount of data being generated through electronic health records and other clinical information systems. This article discusses the asset of clinical data, the multiple roles of nurses in maximizing the value of this asset, and a vision for nursing's future in regards to clinical intelligence. PMID- 22094614 TI - Unraveling care omissions. AB - Evidence points to the omission of required nursing care as a pervasive problem in acute care hospitals. Labor and material resource constraints, increasing patient complexity, ineffective delegation, and poor communication have been identified as contributing factors. Nurse executives should examine the degree and causes of missed care in their organizations. Action plans should be developed based on identification of issues contributing to this serious concern, thus promoting safe patient care. PMID- 22094615 TI - Guiding implementation: frameworks and resources for evidence translation. AB - In this department, Dr Newhouse highlights hot topics in nursing outcomes, research, and evidence-based practice relevant to the nurse administrator. The goal is to discuss practical implications for nurse leaders in diverse healthcare settings. Content includes evidence-based projects and decision making, identifying measurement tools for quality improvement and safety projects, using outcome measures to evaluate quality, practice implications of administrative research, and exemplars of projects that demonstrate innovative approaches to organizational problems. In this article, the authors discuss the need for knowledge translation to leverage improvements in healthcare quality and describe 3 frameworks that can be used to plan and implement translation of evidence to practice. PMID- 22094616 TI - Comparison of patient outcomes in Magnet(r) and non-Magnet hospitals. AB - OBJECTIVE: : This study compared patient outcomes and staffing in Magnet(r) and non-Magnet hospitals. BACKGROUND: : The pursuit of Magnet designation is a highly regarded program for improving staff and patient outcomes. Research has confirmed that Magnet hospitals provide positive work environments for nurses. Research related to patient outcomes in Magnet hospitals is scarce, and results vary. METHODS: : The University Health Systems Consortium provided the clinical and operational databases for the study. Using bivariate and multivariate analyses, a comparison of patient outcomes and nurse staffing in general units and ICUs of Magnet and non-Magnet hospitals was studied. OUTCOMES: : Non-Magnet hospitals had better patient outcomes than Magnet hospitals. Magnet hospitals had slightly better outcomes for pressure ulcers, but infections, postoperative sepsis, and postoperative metabolic derangement outcomes were worse in Magnet hospitals. Magnet hospitals also had lower staffing numbers. CONCLUSIONS: : Magnet hospitals in this study had less total staff and a lower RN skill mix compared with non Magnet hospitals, which contributed to the outcomes. PMID- 22094617 TI - The case for training Veterans Administration frontline nurses in crew resource management. AB - Using cultural analysis, the authors present a rationale for a nursing-focused crew resource management (CRM) program in the Veterans Health Administration. Although the value of CRM in aviation is well documented and CRM has been successfully applied in healthcare settings to improve communication and teamwork, there is little evidence outlining the implementation of CRM on nursing units with nursing as the primary focus. This article describes the preproject data supporting a nursing-focused CRM program called nursing CRM. This is the first in a series of 2 articles highlighting this program. PMID- 22094618 TI - Strategies for retaining midcareer nurses. AB - One method of reducing predicted shortages because of the aging nursing workforce is to increase retention. Few studies have examined the unique needs of midcareer nurses. A mixed-method approach including surveys and focus groups was used to identify key retention strategies and desires for midcareer nurses. Salary, benefits, positive working relationships, flexible scheduling, and the opportunity for continued education were identified as key retention strategies from this study. Registered nurses in this study reported higher perceptions of their work and work environment than licensed practical nurses did. Differences in work outcomes were evident across sectors, with community nurses reporting higher levels of job satisfaction and perceptions of work quality than nurses in acute and long-term care. Findings suggest that recruitment opportunities may exist with midcareer nurses seeking employment to return to work after time off to have a family. Proactive retention policies that focus on the needs of midcareer nurses would demonstrate a commitment and interest in keeping them in their work positions and in the profession. PMID- 22094619 TI - Breaking the fall. AB - OBJECTIVE: : The Helping Hands program is a nurse-directed falls prevention program designed to support a hospital-wide culture of safety and reduce harm from falls. BACKGROUND: : Patient falls and the associated morbidity and mortality represent a significant risk for patients and healthcare facilities. Age-adjusted fatalities from falls increased significantly from 1993 to 2003. By 2020, the annual cost of injuries from falls is expected to exceed $40 billion. METHODS: : Components of the Helping Hands falls prevention program worked synergistically to support the development of a culture of safety at Robert Wood Johnson University Hospital. The program consisted of nursing assessment of fall risk with the Johns Hopkins Fall Risk Assessment Tool; reviews of fall risk and intervention efficacy; creation of communication mechanisms, reporting processes, and change champion roles; engagement of patients and families in falls prevention; increased public awareness of fall risk through signage; nursing interventions; and utilization of nursing performance improvement analysts. RESULTS: : Over 3 years, 65% (N = 7,900) of more than 12,000 patients assessed were at risk of falling. Most falls caused no or little harm, and at 3 years of follow-up, total falls decreased by 16.6 %, and severe falls accounted for 0.009 % (n = 2) of all falls. CONCLUSIONS: : The data offer a hopeful perspective on the role of nursing engagement in developing a hospital-wide culture of safety and protecting patients from permanent harm caused by fall events. PMID- 22094620 TI - Nursing works: the application of lean thinking to nursing processes. AB - This article describes the Nursing Works program at Flinders Medical Centre, South Australia. Program goals were to use lean principles to increase the time direct care nurses spent at the bedside, improve patient outcomes, and make nursing work more efficient and satisfying for staff. Steps incorporating lean methodology are described. Outcomes indicate that lean thinking is an effective improvement methodology and a framework for change management of nursing work. PMID- 22094621 TI - Teaching quality improvement to the next generation of nurses: what nurse managers can do to help. AB - Engaging staff in performance improvement and patient safety initiatives is no easy task. It is not just time that is involved but there is also a definite repertoire of knowledge, skills, and attitudes required. This article describes a win-win venture that assists healthcare agencies in improving current quality improvement activities while actively teaching and vetting students in the process. Nursing students enter the workforce with an appreciation and working knowledge of quality improvement, and agencies gain assistance with their programs and outcomes. PMID- 22094622 TI - Advancing nursing administration through research. PMID- 22094623 TI - Clinical, physiological and anti-inflammatory effect of montelukast in patients with cough variant asthma. AB - BACKGROUND: Cough variant asthma (CVA) is a phenotype of asthma presenting solely with coughing, characterized by airway hyperresponsiveness, eosinophilic inflammation and a cough response to bronchodilators. Leukotriene receptor antagonists (LTRAs) are antiasthma medications with anti-inflammatory and bronchodilatory properties. Although LTRAs exert antitussive effects in CVA, the mechanisms involved are unknown. OBJECTIVES: This study aimed to clarify the antitussive mechanisms of LTRAs in CVA patients. METHODS: We prospectively observed the effect of montelukast (10 mg) daily for 4 weeks in 23 consecutive nonsmoking adults with anti-inflammatory treatment-naive CVA. We evaluated, before and after treatment, the cough visual analogue scale (VAS), pulmonary function (spirometry and impulse oscillation), methacholine airway responsiveness, cough receptor sensitivity, expressed by the concentration of capsaicin inducing 2 or more (C2) and 5 or more (C5) coughs, sputum eosinophil counts and levels of inflammatory mediators, including cysteinyl leukotrienes, leukotriene B(4), prostaglandin (PG) D(2), PGE(2), PGF(2)(alpha) and thromboxane B(2). We compared the baseline characteristics of the patients based on the symptomatic response to montelukast, defined as a decrease in the cough VAS of >25% (n = 15) or <=25% (n = 8). RESULTS: Montelukast significantly decreased the cough VAS (p = 0.0008), sputum eosinophil count (p = 0.013) and cough sensitivity (C2: p = 0.007; C5: p = 0.039), whereas pulmonary function, airway responsiveness and sputum mediator levels remained unchanged. Multivariate analysis showed that a better response to montelukast was associated solely with younger age (p = 0.032). CONCLUSION: The antitussive effect of montelukast in CVA may be attributed to the attenuation of eosinophilic inflammation rather than its bronchodilatory properties. PMID- 22094624 TI - Extension of non-invasive EEG into the kHz range for evoked thalamocortical activity by means of very low noise amplifiers. AB - Ultrafast electroencephalographic signals, having frequencies above 500 Hz, can be observed in somatosensory evoked potential measurements. Usually, these recordings have a poor signal-to-noise ratio (SNR) because weak signals are overlaid by intrinsic noise of much higher amplitude like that generated by biological sources and the amplifier. As an example, recordings at the scalp taken during electrical stimulation of the median nerve show a 600 Hz burst with submicro-volt amplitudes which can be extracted from noise by the use of massive averaging and digital signal processing only. We have investigated this signal by means of a very low noise amplifier made in-house (minimal voltage noise 2.7 nV Hz(-1/2), FET inputs). We examined how the SNR of the data is altered by the bandwidth and the use of amplifiers with different intrinsic amplifier noise levels of 12 and 4.8 nV Hz(-1/2), respectively. By analyzing different frequency contributions of the signal, we found an extremely weak 1 kHz component superimposed onto the well-known 600 Hz burst. Previously such high-frequency electroencephalogram responses around 1 kHz have only been observed by deep brain electrodes implanted for tremor therapy of Parkinson patients. For the non invasive measurement of such signals, we recommend that amplifier noise should not exceed 4 nV Hz(-1/2). PMID- 22094625 TI - Idiopathic short stature: decision making in growth hormone use. AB - Short stature is a common concern in pediatrics. Several ambiguities and controversies persist, especially with regard to criteria, cost, medical necessity and outcomes of growth hormone (GH) therapy for idiopathic short stature (ISS). Due to these ambiguities and controversies, a series of decisions by primary care physicians (whether to refer the short child to a pediatric endocrinologist), pediatric endocrinologist (whether to recommend GH treatment), families (whether to raise concern about short stature and whether to agree to undertake treatment), and third party payers (whether to cover the costs of GH therapy) influence which individual short children will receive GH in the US. Together, these decisions determine overall GH use. Apart from child's growth characteristics, several non-physiological factors drive the critical decisions of these stakeholders. This article focuses on current ambiguities and controversies regarding GH therapy in ISS, discusses the decision-makers involved in GH therapy, and explores the factors influencing their decisions. PMID- 22094626 TI - Management of a Cryptosporidium hominis outbreak in a day-care center. AB - BACKGROUND: Cryptosporidium outbreaks in day-care centers (DCCs) occur commonly. However, controlling spread of infection in these settings is difficult, and data about effectiveness of different control strategies are sparse. In this study, a Cryptosporidium outbreak in a large DCC located in Brussels is described with evaluation of hygienic and therapeutic interventions. METHODS: During a 3-week period, 43 of 130 children attending the DCC developed enteric symptoms. Stools from 122 children were examined for microbial pathogens. Of them, 38 (31%) were diagnosed with Cryptosporidium, 29 of them being symptomatic (76%) and 9 (24%) asymptomatic. Diagnosis was performed by microscopy, antigen tests, and real-time polymerase chain reaction. Strict infection control measures were implemented during the first week after the start of outbreak. After 4 weeks, 27/38 children (71%) were still symptomatic and Cryptosporidium positive. Because of persisting symptoms and fear of further spread of infection, all 27 children were treated with paromomycin. Two weeks later, 18 of 27 children were asymptomatic and were parasitologically negative. The remaining 9 children, still symptomatic and Cryptosporidium positive, were treated with nitazoxanide. Three weeks later, week 9 after the start of outbreak, all 38 children involved in the outbreak were asymptomatic and Cryptosporidium negative. CONCLUSIONS: Our study underscores the need to rule out Cryptosporidium etiology in a diarrheal outbreak in a DCC. Rapid implementation of infection control measures can most likely halt the spread of infection. The role of nitazoxanide to limit duration of shedding of oocysts deserves more attention for its use in outbreaks. PMID- 22094627 TI - Risk factors for systemic Candida infections in pediatric small bowel transplant recipients. AB - BACKGROUND: Fungal infections are an important cause of morbidity and mortality after small bowel transplantation (SBT). Little information about risk factors for Candida infections in pediatric SBT is available. METHODS: We performed a 1:1 matched retrospective case-control study including 23 Candida culture-positive patients (cases) and 23 culture-negative patients (controls), matched based on age and time of transplantation. Patients' characteristics were compared using Wilcoxon rank-sum, chi, or Fisher exact tests. McNemar test was used to assess discordance between pretransplant and posttransplant fungemia. Univariate and multivariable conditional logistic regression analyses were performed to identify risk factors. RESULTS: The median age of the group was 1.87 years (range, 0.87 17.60); 59% patients were male. Within 1 month before transplant, 8.7% cases had fungemia and within 1-6 months before transplant, 30.4% cases had fungemia, compared with 69.6% within the 12 months after transplantation (P = 0.0001 and P = 0.02). By univariate analysis, total parenteral nutrition (TPN) (odds ratio [OR], 17.0 [95% confidence interval: 2.12, 2198]; P = 0.003) and antibiotic administration (OR, 18.99 [2.42, 2449]; P = 0.002) were risk factors for fungal infections. By multivariable analysis, both remained independent risk factors (TPN: OR, 10.86 [1.23, 1425], P = 0.03; antibiotic administration: OR, 12.83 [1.52, 1672], P = 0.01). CONCLUSIONS: Fungemia was significantly more frequent after SBT than before transplantation. Patients receiving TPN and antibiotic treatment had, respectively, 11 and 13 times higher risk of developing Candida infections after SBT. PMID- 22094628 TI - Comparative coverage of supplementary and universally recommended immunizations in children at 24 months of age. AB - BACKGROUND: The introduction of pneumococcal and meningococcal group C conjugate vaccinations as supplementary (a new category in Swiss immunization recommendations) to universally recommended vaccinations in 2006 prompted this study to investigate their acceptance. METHODS: The study was performed in 24 month-old healthy children born in the Geneva or Basel areas in Switzerland between January and April 2007. After informed consent had been obtained from caregivers (for this particular study in Basel and in general for providing immunization data in Geneva on an ongoing basis), all universally recommended and supplementary vaccinations administered by <=24 months of age were analyzed for completeness and timeliness according to set definitions. Sample size calculations and standard statistical tests were applied for comparative data analyses. RESULTS: Of 592 children at the age of 12 months, 94% and 73% had received complete diphtheria-tetanus-pertussis component combination and pneumococcal conjugate vaccinations, respectively. At the age of 24 months, coverage rates for complete booster doses were 77% and 70%, respectively. Rates for MMR doses 1 and 2 at 24 months were 92% and 72%, respectively, and the rate for meningococcal conjugate vaccine (single dose) was 62%. On an average, coverage rates were similar in the 2 study regions except those for pneumococcal conjugate and second dose of MMR, which were approximately 10% higher in Geneva. CONCLUSIONS: Compliance with supplementary vaccinations was lower than that with universally recommended vaccinations. This can be explained by the recent introduction of supplementary vaccinations or by the public perception that they are less important than universal vaccinations. PMID- 22094629 TI - Diagnostic accuracy of cerebrospinal fluid gram stain in children with suspected bacterial meningitis. AB - This cross-sectional study included 1938 children undergoing lumbar puncture; 21 (1.1%) cases were classified as definite (n = 17) or probable (n = 4) bacterial meningitis. Gram stain sensitivity was 94.1% (95% confidence interval, 71.3% 99.9%) for those with definite meningitis; the positive predictive value was 47.1% (95% confidence interval, 29.8%-64.9%). The sensitivity was 95.2% for those with definite or probable meningitis. Antibiotic pretreatment did not affect results. PMID- 22094630 TI - Anti-N-methyl D-aspartate receptor encephalitis mimics viral encephalitis. AB - We describe the clinical courses of 3 children with a psychochoreiform encephalitis associated with anti-N-methyl D-aspartate receptor autoantibodies. These cases, including the most severely medically complicated survivor to date, illustrate the challenges of diagnosis, supportive care, and immune-modulating therapy. Clinical and laboratory features are similar to those of viral encephalitis, and the condition is often reversible with appropriate diagnosis and treatment. PMID- 22094631 TI - Pediatric tuberculosis in Stockholm: a mirror to the world. AB - BACKGROUND: Increasing international migration has changed the epidemiology of tuberculosis (TB) in Europe. Little is published on clinical manifestations and epidemiology in children in this new era. METHODS: Clinical and laboratory data on all children with TB in Stockholm between 2000 and 2009 were entered into a database and retrospectively completed with information from case records. Population data, including parents' country of birth, were obtained from Statistics Sweden. RESULTS: TB was diagnosed in 147 children <18 years of age (78 confirmed, 12 probable, 57 possible). Fifty-six children (38%) presented clinically, and 91 were identified by screening procedures. Ninety children (61%) were born in high-endemic countries and 38 in Sweden to parents from such countries. The incidence was 451/100,000 person years among children born in Somalia, 44 among those born in other high-endemic countries, and 13 among Swedish-born children with parents from high-endemic countries. All but 1 of the 19 Swedish-born children with Swedish parents belonged to a single outbreak. Median age was 12 years. Severe, adult-type TB was predominantly observed in adolescents, whereas young children presented mild, primary disease that was diagnosed at the time of screening. The 78 positive cultures were traced back to 67 strains. Resistance to any first-line drug was present in 25% of the strains, of which 4 were multidrug resistant. CONCLUSIONS: Active TB in Stockholm is common in children born in high-endemic countries, especially Somalia. The most severe cases are seen in adolescents. The high prevalence of antimicrobial resistance is a cause for concern. PMID- 22094632 TI - Influenza vaccine safety in children less than 5 years old: the 2010 and 2011 experience in Australia. AB - In August 2010, the United States Advisory Committee on Immunization Practices recommended that the 2010-2011 CSL seasonal vaccine (Afluria) not be administered to children 6 months to 8 years of age because of the risk of febrile convulsion after immunization. This study reports a low rate (6%-7%) of fever after immunization with 2 non-CSL brands of 2011 seasonal influenza vaccine in Australian children <5 years of age. These data are reassuring for parents and healthcare workers regarding 2011 influenza vaccination in the northern hemisphere. PMID- 22094633 TI - Monitoring of antibiotic resistance rates of Helicobacter pylori in Austrian children, 2002-2009. AB - We retrospectively studied antibiotic resistance rates of H. pylori and their temporal changes in children. Resistance rates were 21.6% for both clarithromycin and metronidazole. There was no overall difference between children with or without migrational background. Resistance rates increased over time, and patients without migrational background showed a significant increase in metronidazole resistance. Our study emphasizes antibiotic resistance monitoring of H. pylori in children. PMID- 22094635 TI - Safety and immunogenicity of a novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants. AB - BACKGROUND: In phase II studies, MenACWY-CRM elicited robust immunologic responses in young infants. We now present results from our pivotal phase III infant immunogenicity/safety study. METHODS: In this open-label phase III study, we randomized full-term 2-month-old infants to 4 doses of MenACWY-CRM coadministered with routine vaccines at 2, 4, 6, and 12 months of age or with routine vaccines alone. We monitored for local and systemic reactions and serious adverse events among all study participants and evaluated for sufficiency of the immune responses to MenACWY-CRM through serum bactericidal activity assay with human complement. RESULTS: Bactericidal antibodies were present in 94% to 100% of subjects against each of the serogroups in MenACWY-CRM after the 4-dose series and were 67% to 97% after the first 3 doses. Geometric mean titers were higher after the fourth dose of MenACWY-CRM compared with a single dose of MenACWY-CRM at 12 months of age for all serogroups (range of ratios, 4.5-38). Responses to 3 doses of routine vaccines coadministered with MenACWY-CRM were noninferior to routine vaccinations alone, except for small differences in pneumococcal serotype 6B responses after dose 3 but not dose 4 and pertactin after dose 3. Inclusion of MenACWY-CRM did not affect the safety or reactogenicity profiles of the routine infant vaccine series. CONCLUSIONS: A 4-dose series of MenACWY-CRM was highly immunogenic and well tolerated in young infants, and it can be coadministered with routine infant vaccines. Substantial immunity was conferred after the first 3 doses administered at 2, 4, and 6 months of age. PMID- 22094636 TI - A randomized trial to assess safety and immunogenicity of alternative formulations of a quadrivalent meningococcal (A, C, Y, and W-135) tetanus protein conjugate vaccine in toddlers. AB - BACKGROUND: Neisseria meningitidis is a leading cause of meningitis and septicemia globally. Recent shifts in serogroup dominance in some settings highlight the desirability of polysaccharide-conjugate vaccines with broader meningococcal coverage than serogroup C vaccines in widespread use. METHODS: We assessed the safety and immunogenicity of a single dose of meningococcal quadrivalent (A, C, W-135, Y) tetanus conjugate vaccine (TetraMen-T), administered at 1 year of age. A total of 378 children were randomized to 1 of 6 groups--5 received alternative formulations of TetraMen-T, the sixth licensed adjuvanted serogroup C conjugate vaccine (Neisvac-C). Solicited adverse event reports were collected from day 0 to 7 after vaccination and unsolicited and serious adverse event reports throughout study participation. Immunogenicity was assessed by serum bactericidal assays containing either a human (hSBA) or baby rabbit (rSBA) complement source before and 1 month after immunization. RESULTS: All vaccine formulations were safe and well tolerated. Using the various measures of immunogenicity, no consistent relationships were observed between the dose of either polysaccharide or carrier and serogroup-specific response for any one antigen. The highest-dose vaccine provided optimal coverage for all 4 serogroups, with the percentage of recipients achieving hSBA titers >= 8 against each as follows: A, 92%; C, 96%; W-135, 71%; Y, 82% (corresponding proportions with rSBAs titers >8 all exceeded 90%). The investigational vaccines were less immunogenic against the serogroup C capsular polysaccharide than the licensed comparator. CONCLUSIONS: Studies are ongoing that will help to identify optimal scheduling of quadrivalent meningococcal conjugate vaccines, to facilitate their inclusion into national immunization programs seeking extended serogroup coverage against meningococci. PMID- 22094638 TI - Proving etiologic relationships to disease: the particular problem of human coronaviruses. PMID- 22094637 TI - Human coronavirus in young children hospitalized for acute respiratory illness and asymptomatic controls. AB - BACKGROUND: Human coronaviruses (HCoVs) have been detected in children with upper and lower respiratory symptoms, but little is known about their relationship with severe respiratory illness. OBJECTIVE: To compare the prevalence of HCoV species among children hospitalized for acute respiratory illness and/or fever (ARI/fever) with that among asymptomatic controls and to assess the severity of outcomes among hospitalized children with HCoV infection compared with other respiratory viruses. METHODS: From December 2003 to April 2004 and October 2004 to April 2005, we conducted prospective, population-based surveillance of children <5 years of age hospitalized for ARI/fever in 3 US counties. Asymptomatic outpatient controls were enrolled concurrently. Nasal/throat swabs were tested for HCoV species HKU1, NL63, 229E, and OC43 by real-time reverse transcription polymerase chain reaction. Specimens from hospitalized children were also tested for other common respiratory viruses. Demographic and medical data were collected by parent/guardian interview and medical chart review. RESULTS: Overall, HCoV was detected in 113 (7.6%) of 1481 hospitalized children (83 [5.7%] after excluding 30 cases coinfected with other viruses) and 53 (7.1%) of 742 controls. The prevalence of HCoV or individual species was not significantly higher among hospitalized children than controls. Hospitalized children testing positive for HCoV alone tended to be less ill than those infected with other viruses, whereas those coinfected with HCoV and other viruses were clinically similar to those infected with other viruses alone. CONCLUSIONS: In this study of children hospitalized for ARI/fever, HCoV infection was not associated with hospitalization or with increased severity of illness. PMID- 22094639 TI - Diagnostic features associated with culture of Mycobacterium tuberculosis among young children in a vaccine trial setting. AB - OBJECTIVES: To identify diagnostic features associated with culture of Mycobacterium tuberculosis (MTB), the standard for tuberculosis (TB) diagnosis, to inform clinical end point definitions for new TB vaccine trials. METHODS: Children <2 years of age (n = 1445) were screened and investigated for TB during a Bacille Calmette Guerin vaccine trial in South Africa. Standardized clinical, radiologic, and microbiologic data were collected, including paired gastric lavage and induced sputum for MTB liquid culture. Adjusted odds ratios (AORs) were calculated using a multivariate logistic regression model. RESULTS: Adjusted odds of positive MTB culture increased by 90% with history of wheezing (AOR, 1.9) and by 4% with each 1-mm increase in Mantoux diameter (AOR, 1.04). Odds of positive MTB culture doubled if the chest radiograph was suggestive of pulmonary TB (AOR, 2.16) and more than tripled if lower chest retraction was observed clinically (AOR, 3.37). Fever, night sweats, and presence of lymphadenopathy were negatively associated with MTB culture (AOR: 0.5, 0.62, and 0.2, respectively). Persistent cough, weight loss, and failure to thrive were not significantly associated with MTB culture in this study population. CONCLUSIONS: Wheezing and lower chest retraction, consistent with intrathoracic airway obstruction; chest radiography suggestive of pulmonary tuberculosis; and Mantoux diameter were predictive of positive MTB culture. These variables should be considered for inclusion in composite clinical end point definitions for infant TB vaccine trials. Several clinical features, commonly used for TB diagnosis in older children, were not associated with positive MTB culture among children younger than 2 years. PMID- 22094640 TI - High prevalence of acute respiratory tract infections among Warao Amerindian children in Venezuela in relation to low immunization coverage and chronic malnutrition. AB - BACKGROUND: Higher prevalence rates of acute respiratory tract infections (ARTIs) have been described in Australian and Canadian indigenous populations than in nonindigenous age-matched counterparts. Few studies on ARTIs in South American indigenous populations have been published. We performed a cross-sectional survey to describe the prevalence of upper respiratory tract infections and acute lower respiratory tract infections (ALRTIs) and associations with malnutrition and immunization status. METHODS: From December 1, 2009 to May 31, 2010, 487 Warao Amerindian children 0 to 59 months of age living in the Delta Amacuro in Venezuela were included in a cross-sectional survey. Data were obtained through parent questionnaires, vaccination cards, and physical examinations including anthropometric measurements. RESULTS: Of the 487 children, 47% presented with an ARTI. Of these, 60% had upper respiratory tract infections and 40% were ALRTI. Immunization coverage was low, with only 27% of all children presenting a vaccination card being fully immunized. The prevalence of malnutrition was high (52%), with stunting (height-for-age <-2 standard deviations) being the most frequent presentation affecting 45% of children. ARTI and ALRTI prevalence diminished with increasing age (odds ratio for ALRTI in children 25-59 months of age vs. children younger than 12 months, 0.49; 95% confidence interval, 0.26 0.93). Furthermore, significant differences in ARTI prevalence were seen between villages. No significant associations between immunization status or malnutrition and ARTI or ALRTI prevalence were identified. CONCLUSIONS: A high prevalence of ARTIs and chronic malnutrition in combination with a low immunization status highlights the need for an integrated approach to improve the health status of indigenous Venezuelan children. PMID- 22094641 TI - Levels of kinesin light chain and dynein intermediate chain are reduced in the frontal cortex in Alzheimer's disease: implications for axoplasmic transport. AB - Fast anterograde and retrograde axoplasmic transports in neurons rely on the activity of molecular motors and are critical for maintenance of neuronal and synaptic functions. Disturbances of axoplasmic transport have been identified in Alzheimer's disease and in animal models of this disease, but their mechanisms are not well understood. In this study we have investigated the distribution and the level of expression of kinesin light chains (KLCs) (responsible for binding of cargos during anterograde transport) and of dynein intermediate chain (DIC) (a component of the dynein complex during retrograde transport) in frontal cortex and cerebellar cortex of control subjects and Alzheimer's disease patients. By immunoblotting, we found a significant decrease in the levels of expression of KLC1 and 2 and DIC in the frontal cortex, but not in the cerebellar cortex, of Alzheimer's disease patients. A significant decrease in the levels of synaptophysin and of tubulin-beta3 proteins, two neuronal markers, was also observed. KLC1 and DIC immunoreactivities did not co-localize with neurofibrillary tangles. The mean mRNA levels of KLC1, 2 and DIC were not significantly different between controls and AD patients. In SH-SY5Y neural cells, GSK-3beta phosphorylated KLC1, a change associated to decreased association of KLC1 with its cargoes. Increased levels of active GSK-3beta and of phosphorylated KLC1 were also observed in AD frontal cortex. We suggest that reduction of KLCs and DIC proteins in AD cortex results from both reduced expression and neuronal loss, and that these reductions and GSK-3beta-mediated phosphorylation of KLC1 contribute to disturbances of axoplasmic flows and synaptic integrity in Alzheimer's disease. PMID- 22094643 TI - Effects of network resolution on topological properties of human neocortex. AB - Graph theoretical analyses applied to neuroimaging datasets have provided valuable insights into the large-scale anatomical organization of the human neocortex. Most of these studies were performed with different cortical scales leading to cortical networks with different levels of small-world organization. The present study investigates how resolution of thickness-based cortical scales impacts on topological properties of human anatomical cortical networks. To this end, we designed a novel approach aimed at determining the best trade-off between small-world attributes of anatomical cortical networks and the number of cortical regions included in the scale. Results revealed that schemes comprising 540-599 regions (surface areas spanning between 250 and 275 mm(2)) at sparsities below 10% showed a superior balance between small-world organization and the size of the cortical scale employed. Furthermore, we found that the cortical scale representing the best trade-off (599 regions) was more resilient to targeted attacks than atlas-based schemes (Desikan-Killiany atlas, 66 regions) and, most importantly, it did not differ that much from the finest cortical scale tested in the present study (1494 regions). In summary, our study confirms that topological organization of anatomical cortical networks varies with both sparsity and resolution of cortical scale, and it further provides a novel methodological framework aimed at identifying cortical schemes that maximize small-worldness with the lowest scale resolution possible. PMID- 22094642 TI - Diagnostic neuroimaging across diseases. AB - Fully automated classification algorithms have been successfully applied to diagnose a wide range of neurological and psychiatric diseases. They are sufficiently robust to handle data from different scanners for many applications and in specific cases outperform radiologists. This article provides an overview of current applications taking structural imaging in Alzheimer's disease and schizophrenia as well as functional imaging to diagnose depression as examples. In this context, we also report studies aiming to predict the future course of the disease and the response to treatment for the individual. This has obvious clinical relevance but is also important for the design of treatment studies that may aim to include a cohort with a predicted fast disease progression to be more sensitive to detect treatment effects. In the second part, we present our own opinions on i) the role these classification methods can play in the clinical setting; ii) where their limitations are at the moment and iii) how those can be overcome. Specifically, we discuss strategies to deal with disease heterogeneity, diagnostic uncertainties, a probabilistic framework for classification and multi class classification approaches. PMID- 22094645 TI - Simultaneous segmentation and grading of anatomical structures for patient's classification: application to Alzheimer's disease. AB - In this paper, we propose an innovative approach to robustly and accurately detect Alzheimer's disease (AD) based on the distinction of specific atrophic patterns of anatomical structures such as hippocampus (HC) and entorhinal cortex (EC). The proposed method simultaneously performs segmentation and grading of structures to efficiently capture the anatomical alterations caused by AD. Known as SNIPE (Scoring by Non-local Image Patch Estimator), the novel proposed grading measure is based on a nonlocal patch-based frame-work and estimates the similarity of the patch surrounding the voxel under study with all the patches present in different training populations. In this study, the training library was composed of two populations: 50 cognitively normal subjects (CN) and 50 patients with AD, randomly selected from the ADNI database. During our experiments, the classification accuracy of patients (CN vs. AD) using several biomarkers was compared: HC and EC volumes, the grade of these structures and finally the combination of their volume and their grade. Tests were completed in a leave-one-out framework using discriminant analysis. First, we showed that biomarkers based on HC provide better classification accuracy than biomarkers based on EC. Second, we demonstrated that structure grading is a more powerful measure than structure volume to distinguish both populations with a classification accuracy of 90%. Finally, by adding the ages of subjects in order to better separate age-related structural changes from disease-related anatomical alterations, SNIPE obtained a classification accuracy of 93%. PMID- 22094646 TI - Conditions for highly efficient and reproducible round-window stimulation in humans. AB - Round-window stimulation is a new clinical approach for the application of active middle-ear implants. To investigate factors influencing the efficiency of round window stimulation, experiments in 6 human temporal bones were performed with different actuator geometries and coupling conditions. The experiments show that the amplitude ratio between stapes and round-window actuator vibration is most efficient when using a 1.0-mm diameter rod with a 30 degrees inclined tip geometry and an attached silicone pad. In this case, the amplitude ratio is 0.34 for frequencies up to 1.5 kHz and 0.27 for frequencies up to 20 kHz, with a standard deviation of only 4-6 dB at most frequencies. The analysis of data presented here and in a companion paper suggests that control of proper round window membrane pretension as well as the inclined tip geometry are the major requirements for maximal performance. PMID- 22094644 TI - Along-tract statistics allow for enhanced tractography analysis. AB - Diffusion imaging tractography is a valuable tool for neuroscience researchers because it allows the generation of individualized virtual dissections of major white matter tracts in the human brain. It facilitates between-subject statistical analyses tailored to the specific anatomy of each participant. There is prominent variation in diffusion imaging metrics (e.g., fractional anisotropy, FA) within tracts, but most tractography studies use a "tract-averaged" approach to analysis by averaging the scalar values from the many streamline vertices in a tract dissection into a single point-spread estimate for each tract. Here we describe a complete workflow needed to conduct an along-tract analysis of white matter streamline tract groups. This consists of 1) A flexible MATLAB toolkit for generating along-tract data based on B-spline resampling and compilation of scalar data at different collections of vertices along the curving tract spines, and 2) Statistical analysis and rich data visualization by leveraging tools available through the R platform for statistical computing. We demonstrate the effectiveness of such an along-tract approach over the tract-averaged approach in an example analysis of 10 major white matter tracts in a single subject. We also show that these techniques easily extend to between-group analyses typically used in neuroscience applications, by conducting an along-tract analysis of differences in FA between 9 individuals with fetal alcohol spectrum disorders (FASDs) and 11 typically-developing controls. This analysis reveals localized differences between FASD and control groups that were not apparent using a tract averaged method. Finally, to validate our approach and highlight the strength of this extensible software framework, we implement 2 other methods from the literature and leverage the existing workflow tools to conduct a comparison study. PMID- 22094647 TI - Pharmacotherapeutic implications of the association between genomic instability at chromosome 15q13.3 and autism spectrum disorders. AB - Recurrent microdeletions of chromosome 15q13.3 are causally associated with autism spectrum disorders (ASDs), suggesting that haploinsufficiency of CHRNA7, the gene that codes for the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) subunit, is an etiological mechanism. Independent of these genetic data, given the location of alpha7 nAChRs on gamma-aminobutyric acid-inhibitory neurons and their role in maintaining central inhibitory tone, a compelling pharmacological rationale exists for therapeutically targeting the alpha7 nAChR in persons with ASDs. Given the availability of positive allosteric modulators of nicotinic acetylcholine receptors and selective agonists for the alpha7 nAChR (eg, choline derived from dietary administration of cytidine 5'diphosphocholine and anabasine derivatives), it is possible to conduct "proof of concept" clinical trials, exploring the effects of alpha7 nAChR agonist interventional strategies on domains of psychopathology, such as attention, cognition, and memory, in persons with ASDs. PMID- 22094648 TI - Complexity of motor response to different doses of duodenal levodopa infusion in Parkinson disease. AB - OBJECTIVE: The aim was to elaborately describe individual pharmacokinetic pharmacodynamic profiles in patients with difficult-to-treat dyskinesias treated with levodopa/carbidopa intestinal gel infusion. METHODS: A nonrandomized, partly blinded, investigator-initiated trial was conducted in 5 patients with idiopathic Parkinson disease who were difficult to keep in "on" state without dyskinesia. Levodopa/carbidopa intestinal gel (Duodopa) doses of 80% to 120% of individually and clinically optimized dosage were infused during five 4-hour periods. Pharmacokinetic profiling, blinded assessment of video recordings, and objective movement analysis were applied every 20 to 30 minutes. RESULTS: Individual correlations between plasma levodopa concentrations and corresponding motor scores 20 to 30 minutes after the sampling time were significant in all patients (P < 0.05 and P < 0.001). Motor scores were generally stable during the 4-hour periods. The objective test revealed that motor performance was faster the more dyskinetic the patients were. Mean individual Treatment Response Scale scores were positive in 24 of the 25 steady-state periods. Dystonia was always combined with choreic dyskinesias. CONCLUSIONS: Motor response from different doses of levodopa/carbidopa intestinal gel is in a broad sense predictable even in dyskinetic patients although major interindividual differences in dose requirement, plasma levels, and motor response are found. That motor performance was faster the more dyskinetic the patients were implies that motor performance may be better with moderate dyskinesia than with mild dyskinesia. This may explain why patients with persistent dyskinesias choose to keep their doses above the dyskinesia threshold. There is no ideal therapeutic window in such patients, but levodopa infusion offers stable motor response. PMID- 22094649 TI - Desirable partners. PMID- 22094650 TI - Climate change. PMID- 22094651 TI - Ex factor. PMID- 22094652 TI - Time to stop celebrating the polluters. PMID- 22094663 TI - Russia gets the red planet blues. PMID- 22094664 TI - China forges ahead in space. PMID- 22094665 TI - Gulf ecology hit by coastal development. PMID- 22094666 TI - Depression drug disappoints. PMID- 22094667 TI - Summit urged to clean up farming. PMID- 22094669 TI - Iran's nuclear plan revealed. PMID- 22094668 TI - Targeted treatment tested as potential cancer cure. PMID- 22094670 TI - Research at Janelia: life on the farm. PMID- 22094671 TI - Dark days of the Triassic: lost world. PMID- 22094672 TI - Climate policy: letting go of Kyoto. PMID- 22094673 TI - Environmental science: good governance for geoengineering. PMID- 22094679 TI - Antarctica: fishery threatens protected ocean. PMID- 22094681 TI - Agriculture: risk assessment for Brazil's GM bean. PMID- 22094683 TI - Herbert Hauptman (1917-2011). PMID- 22094684 TI - Ageing: generations of longevity. PMID- 22094685 TI - Quantum physics: shaking photons out of the vacuum. PMID- 22094686 TI - Geophysics: earth's longest fossil rift-valley system. PMID- 22094687 TI - Neuroscience: chemical ecology of pain. PMID- 22094688 TI - Quantum information: the conundrum of secure positioning. PMID- 22094689 TI - Silicon electronics and beyond. PMID- 22094690 TI - Multigate transistors as the future of classical metal-oxide-semiconductor field effect transistors. AB - For more than four decades, transistors have been shrinking exponentially in size, and therefore the number of transistors in a single microelectronic chip has been increasing exponentially. Such an increase in packing density was made possible by continually shrinking the metal-oxide-semiconductor field-effect transistor (MOSFET). In the current generation of transistors, the transistor dimensions have shrunk to such an extent that the electrical characteristics of the device can be markedly degraded, making it unlikely that the exponential decrease in transistor size can continue. Recently, however, a new generation of MOSFETs, called multigate transistors, has emerged, and this multigate geometry will allow the continuing enhancement of computer performance into the next decade. PMID- 22094691 TI - Nanometre-scale electronics with III-V compound semiconductors. AB - For 50 years the exponential rise in the power of electronics has been fuelled by an increase in the density of silicon complementary metal-oxide-semiconductor (CMOS) transistors and improvements to their logic performance. But silicon transistor scaling is now reaching its limits, threatening to end the microelectronics revolution. Attention is turning to a family of materials that is well placed to address this problem: group III-V compound semiconductors. The outstanding electron transport properties of these materials might be central to the development of the first nanometre-scale logic transistors. PMID- 22094692 TI - Academic and industry research progress in germanium nanodevices. AB - Silicon has enabled the rise of the semiconductor electronics industry, but it was not the first material used in such devices. During the 1950s, just after the birth of the transistor, solid-state devices were almost exclusively manufactured from germanium. Today, one of the key ways to improve transistor performance is to increase charge-carrier mobility within the device channel. Motivated by this, the solid-state device research community is returning to investigating the high mobility material germanium. Germanium-based transistors have the potential to operate at high speeds with low power requirements and might therefore be used in non-silicon-based semiconductor technology in the future. PMID- 22094693 TI - Tunnel field-effect transistors as energy-efficient electronic switches. AB - Power dissipation is a fundamental problem for nanoelectronic circuits. Scaling the supply voltage reduces the energy needed for switching, but the field-effect transistors (FETs) in today's integrated circuits require at least 60 mV of gate voltage to increase the current by one order of magnitude at room temperature. Tunnel FETs avoid this limit by using quantum-mechanical band-to-band tunnelling, rather than thermal injection, to inject charge carriers into the device channel. Tunnel FETs based on ultrathin semiconducting films or nanowires could achieve a 100-fold power reduction over complementary metal-oxide-semiconductor (CMOS) transistors, so integrating tunnel FETs with CMOS technology could improve low power integrated circuits. PMID- 22094694 TI - A role for graphene in silicon-based semiconductor devices. AB - As silicon-based electronics approach the limit of improvements to performance and capacity through dimensional scaling, attention in the semiconductor field has turned to graphene, a single layer of carbon atoms arranged in a honeycomb lattice. Its high mobility of charge carriers (electrons and holes) could lead to its use in the next generation of high-performance devices. Graphene is unlikely to replace silicon completely, however, because of the poor on/off current ratio resulting from its zero bandgap. But it could be used to improve silicon-based devices, in particular in high-speed electronics and optical modulators. PMID- 22094695 TI - Embracing the quantum limit in silicon computing. AB - Quantum computers hold the promise of massive performance enhancements across a range of applications, from cryptography and databases to revolutionary scientific simulation tools. Such computers would make use of the same quantum mechanical phenomena that pose limitations on the continued shrinking of conventional information processing devices. Many of the key requirements for quantum computing differ markedly from those of conventional computers. However, silicon, which plays a central part in conventional information processing, has many properties that make it a superb platform around which to build a quantum computer. PMID- 22094696 TI - Environmental effects of information and communications technologies. AB - The digital revolution affects the environment on several levels. Most directly, information and communications technology (ICT) has environmental impacts through the manufacturing, operation and disposal of devices and network equipment, but it also provides ways to mitigate energy use, for example through smart buildings and teleworking. At a broader system level, ICTs influence economic growth and bring about technological and societal change. Managing the direct impacts of ICTs is more complex than just producing efficient devices, owing to the energetically expensive manufacturing process, and the increasing proliferation of devices needs to be taken into account. PMID- 22094697 TI - Observation of the dynamical Casimir effect in a superconducting circuit. AB - One of the most surprising predictions of modern quantum theory is that the vacuum of space is not empty. In fact, quantum theory predicts that it teems with virtual particles flitting in and out of existence. Although initially a curiosity, it was quickly realized that these vacuum fluctuations had measurable consequences--for instance, producing the Lamb shift of atomic spectra and modifying the magnetic moment of the electron. This type of renormalization due to vacuum fluctuations is now central to our understanding of nature. However, these effects provide indirect evidence for the existence of vacuum fluctuations. From early on, it was discussed whether it might be possible to more directly observe the virtual particles that compose the quantum vacuum. Forty years ago, it was suggested that a mirror undergoing relativistic motion could convert virtual photons into directly observable real photons. The phenomenon, later termed the dynamical Casimir effect, has not been demonstrated previously. Here we observe the dynamical Casimir effect in a superconducting circuit consisting of a coplanar transmission line with a tunable electrical length. The rate of change of the electrical length can be made very fast (a substantial fraction of the speed of light) by modulating the inductance of a superconducting quantum interference device at high frequencies (>10 gigahertz). In addition to observing the creation of real photons, we detect two-mode squeezing in the emitted radiation, which is a signature of the quantum character of the generation process. PMID- 22094698 TI - Atom-resolved imaging of ordered defect superstructures at individual grain boundaries. AB - The ability to resolve spatially and identify chemically atoms in defects would greatly advance our understanding of the correlation between structure and property in materials. This is particularly important in polycrystalline materials, in which the grain boundaries have profound implications for the properties and applications of the final material. However, such atomic resolution is still extremely difficult to achieve, partly because grain boundaries are effective sinks for atomic defects and impurities, which may drive structural transformation of grain boundaries and consequently modify material properties. Regardless of the origin of these sinks, the interplay between defects and grain boundaries complicates our efforts to pinpoint the exact sites and chemistries of the entities present in the defective regions, thereby limiting our understanding of how specific defects mediate property changes. Here we show that the combination of advanced electron microscopy, spectroscopy and first-principles calculations can provide three-dimensional images of complex, multicomponent grain boundaries with both atomic resolution and chemical sensitivity. The high resolution of these techniques allows us to demonstrate that even for magnesium oxide, which has a simple rock-salt structure, grain boundaries can accommodate complex ordered defect superstructures that induce significant electron trapping in the bandgap of the oxide. These results offer insights into interactions between defects and grain boundaries in ceramics and demonstrate that atomic-scale analysis of complex multicomponent structures in materials is now becoming possible. PMID- 22094700 TI - East Antarctic rifting triggers uplift of the Gamburtsev Mountains. AB - The Gamburtsev Subglacial Mountains are the least understood tectonic feature on Earth, because they are completely hidden beneath the East Antarctic Ice Sheet. Their high elevation and youthful Alpine topography, combined with their location on the East Antarctic craton, creates a paradox that has puzzled researchers since the mountains were discovered in 1958. The preservation of Alpine topography in the Gamburtsevs may reflect extremely low long-term erosion rates beneath the ice sheet, but the mountains' origin remains problematic. Here we present the first comprehensive view of the crustal architecture and uplift mechanisms for the Gamburtsevs, derived from radar, gravity and magnetic data. The geophysical data define a 2,500-km-long rift system in East Antarctica surrounding the Gamburtsevs, and a thick crustal root beneath the range. We propose that the root formed during the Proterozoic assembly of interior East Antarctica (possibly about 1 Gyr ago), was preserved as in some old orogens and was rejuvenated during much later Permian (roughly 250 Myr ago) and Cretaceous (roughly 100 Myr ago) rifting. Much like East Africa, the interior of East Antarctica is a mosaic of Precambrian provinces affected by rifting processes. Our models show that the combination of rift-flank uplift, root buoyancy and the isostatic response to fluvial and glacial erosion explains the high elevation and relief of the Gamburtsevs. The evolution of the Gamburtsevs demonstrates that rifting and preserved orogenic roots can produce broad regions of high topography in continental interiors without significantly modifying the underlying Precambrian lithosphere. PMID- 22094699 TI - Observed increase in local cooling effect of deforestation at higher latitudes. AB - Deforestation in mid- to high latitudes is hypothesized to have the potential to cool the Earth's surface by altering biophysical processes. In climate models of continental-scale land clearing, the cooling is triggered by increases in surface albedo and is reinforced by a land albedo-sea ice feedback. This feedback is crucial in the model predictions; without it other biophysical processes may overwhelm the albedo effect to generate warming instead. Ongoing land-use activities, such as land management for climate mitigation, are occurring at local scales (hectares) presumably too small to generate the feedback, and it is not known whether the intrinsic biophysical mechanism on its own can change the surface temperature in a consistent manner. Nor has the effect of deforestation on climate been demonstrated over large areas from direct observations. Here we show that surface air temperature is lower in open land than in nearby forested land. The effect is 0.85 +/- 0.44 K (mean +/- one standard deviation) northwards of 45 degrees N and 0.21 +/- 0.53 K southwards. Below 35 degrees N there is weak evidence that deforestation leads to warming. Results are based on comparisons of temperature at forested eddy covariance towers in the USA and Canada and, as a proxy for small areas of cleared land, nearby surface weather stations. Night-time temperature changes unrelated to changes in surface albedo are an important contributor to the overall cooling effect. The observed latitudinal dependence is consistent with theoretical expectation of changes in energy loss from convection and radiation across latitudes in both the daytime and night-time phase of the diurnal cycle, the latter of which remains uncertain in climate models. PMID- 22094701 TI - Spalt mediates an evolutionarily conserved switch to fibrillar muscle fate in insects. AB - Flying insects oscillate their wings at high frequencies of up to 1,000 Hz and produce large mechanical forces of 80 W per kilogram of muscle. They utilize a pair of perpendicularly oriented indirect flight muscles that contain fibrillar, stretch-activated myofibres. In contrast, all other, more slowly contracting, insect body muscles have a tubular muscle morphology. Here we identify the transcription factor Spalt major (Salm) as a master regulator of fibrillar flight muscle fate in Drosophila. salm is necessary and sufficient to induce fibrillar muscle fate. salm switches the entire transcriptional program from tubular to fibrillar fate by regulating the expression and splicing of key sarcomeric components specific to each muscle type. Spalt function is conserved in insects evolutionarily separated by 280 million years. We propose that Spalt proteins switch myofibres from tubular to fibrillar fate during development, a function potentially conserved in the vertebrate heart--a stretch-activated muscle sharing features with insect flight muscle. PMID- 22094704 TI - Mapping of Chagas disease research: analysis of publications in the period between 1940 and 2009. AB - INTRODUCTION: Publications are often used as a measure of success in research work. Chagas disease occurs in Central and Southern America. However, during the past years, the disease has been occurring outside Latin America due to migration from endemic zones. This article describes a bibliometric review of the literature on Chagas disease research indexed in PubMed during a 70-year period. METHODS: Medline was used via the PubMed online service of the U.S. National Library of Medicine from 1940 to 2009. The search strategy was: Chagas disease [MeSH] OR Trypanosoma cruzi [MeSH]. RESULTS: A total of 13,989 references were retrieved. The number of publications increased steadily over time from 1,361 (1940-1969) to 5,430 (2000-2009) (coefficient of determination for linear fit, R2=0.910). Eight journals contained 25% of the Chagas disease literature. Of the publications, 64.2% came from endemic countries. Brazil was the predominant country (37%), followed by the United States (17.6%) and Argentina (14%). The ranking in production changed when the number of publications was normalized by estimated cases of Chagas disease (Panama and Uruguay), population (Argentina and Uruguay), and gross domestic product (Bolivia and Brazil). CONCLUSIONS: Several Latin American countries, where the prevalence of T. cruzi infection was not very high, were the main producers of the Chagas disease literature, after adjusting for economic and population indexes. The countries with more estimated cases of Chagas disease produced less research on Chagas disease than some developed countries. PMID- 22094705 TI - Risk factors for Leishmania chagasi infection in an endemic area in Raposa, State of Maranhao, Brazil. AB - INTRODUCTION: Infection with Leishmania chagasi is the most common clinical presentation for visceral leishmaniaisis in endemic areas. The municipality of Raposa is an endemic area in State of Maranhao, Brazil, and have had registration cases of visceral leishmaniasis disease. For this reason, a cross-sectional study was conducted to evaluate the risk factors for infection with L. chagasi detected by Montenegro skin test. METHODS: The sample comprised 96% of the inhabitants of the villages of Maresia, Pantoja, and Marisol located in the municipality of Raposa, corresponding to 1,359 subjects. Data were collected using a questionnaire. Univariate and multivariate logistic regression models were applied to evaluate the association between the variables studied and infection of L. chagasi. RESULTS: The variables associated with infection upon nonadjusted analysis were a straw roof, mud walls, floors of beaten earth, presence of sand flies inside or outside of the dwelling, and bathing outdoors. Adjusted analysis showed that the presence of sand flies inside/outside the dwelling was a risk factor, and age younger than 10 years was a protective factor against asymptomatic infection. CONCLUSIONS: The results highlight the extent to which precarious living conditions of the population strengthen the epidemiological chain of visceral leishmaniasis. PMID- 22094706 TI - Molecular characterization of Trypanosoma cruzi Mexican strains and their behavior in the mouse experimental model. AB - INTRODUCTION: For a long time, the importance of Chagas disease in Mexico, where many regarded it as an exotic malady, was questioned. Considering the great genetic diversity among isolates of Trypanosoma cruzi, the importance of this biological characterization, and the paucity of information on the clinical and biological aspects of Chagas disease in Mexico, this study aimed to identify the molecular and biological characterization of Trypanosoma cruzi isolates from different endemic areas of this country, especially of the State of Jalisco. METHODS: Eight Mexican Trypanosoma cruzi strains were biologically and genetically characterized (PCR specific for Trypanosoma cruzi, multiplex-PCR, amplification of space no transcript of the genes of the mini-exon, amplification of polymorphic regions of the mini-exon, classification by amplification of intergenic regions of the spliced leader genes, RAPD (random amplified polymorphic DNA). RESULTS: Two profiles of parasitaemia were observed, patent (peak parasitaemia of 4.6*10(6) to 10(7) parasites/mL) and subpatent. In addition, all isolates were able to infect 100% of the animals. The isolates mainly displayed tropism for striated (cardiac and skeletal) muscle. PCR amplification of the mini-exon gene classified the eight strains as TcI. The RAPD technique revealed intraspecies variation among isolates, distinguishing strains isolated from humans and triatomines and according to geographic origin. CONCLUSIONS: The Mexican T. cruzi strains are myotrophic and belong to group TcI. PMID- 22094702 TI - A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain. AB - Natural products that elicit discomfort or pain represent invaluable tools for probing molecular mechanisms underlying pain sensation. Plant-derived irritants have predominated in this regard, but animal venoms have also evolved to avert predators by targeting neurons and receptors whose activation produces noxious sensations. As such, venoms provide a rich and varied source of small molecule and protein pharmacophores that can be exploited to characterize and manipulate key components of the pain-signalling pathway. With this in mind, here we perform an unbiased in vitro screen to identify snake venoms capable of activating somatosensory neurons. Venom from the Texas coral snake (Micrurus tener tener), whose bite produces intense and unremitting pain, excites a large cohort of sensory neurons. The purified active species (MitTx) consists of a heteromeric complex between Kunitz- and phospholipase-A2-like proteins that together function as a potent, persistent and selective agonist for acid-sensing ion channels (ASICs), showing equal or greater efficacy compared with acidic pH. MitTx is highly selective for the ASIC1 subtype at neutral pH; under more acidic conditions (pH < 6.5), MitTx massively potentiates (>100-fold) proton-evoked activation of ASIC2a channels. These observations raise the possibility that ASIC channels function as coincidence detectors for extracellular protons and other, as yet unidentified, endogenous factors. Purified MitTx elicits robust pain related behaviour in mice by activation of ASIC1 channels on capsaicin-sensitive nerve fibres. These findings reveal a mechanism whereby snake venoms produce pain, and highlight an unexpected contribution of ASIC1 channels to nociception. PMID- 22094707 TI - Enteric parasites in HIV-1/AIDS-infected patients from a Northwestern Sao Paulo reference unit in the highly active antiretroviral therapy era. AB - INTRODUCTION: We describe the epidemiology of intestinal parasites in patients from an AIDS reference service in Northeastern Sao Paulo, Brazil. METHODS: Retrospective evaluation was done for all HIV-1/AIDS-positive patients whose Hospital de Base/Sao Jose do Rio Preto laboratorial analysis was positive for enteroparasites after diagnosis of HIV-1 infection, from January 1998 to December 2008. Statistical analysis was performed using the R statistical software version 2.4.1. The level of significance adopted was 5%. RESULTS: The most frequent protozoan was Isospora belli (4.2%), followed by Giardia lamblia (3.5%), Entamoeba coli (2.8%), and Cryptosporidium parvum (0.3%). Ancylostoma duodenale (1.4%) was the most frequently detected helminth, while Taenia saginata and Strongiloides stercoralis were found in 0.7% of the samples. The results showed that diarrhea was significantly associated with giardiasis and isosporiasis. However, no association was observed between CD4+ cell counts, viral load, and the characteristics of any particular parasite. CONCLUSIONS: Our data may be useful for further comparisons with other Brazilian regions and other developing countries. The data may also provide important clues toward improving the understanding, prevention, and control of enteric parasites around the world. PMID- 22094708 TI - Molecular analysis and dimorphism of azole-susceptible and resistant Candida albicans isolates. AB - INTRODUCTION: Candida albicans is responsible for superficial or systemic infections known as candidiasis, which may be found in infected tissue as unicellular budding yeasts, hyphae, or pseudohyphae. In this study, the effects of both fluconazole and itraconazole antifungal agents on the hyphal formation and genotypic characterization of C. albicans isolates classified as either susceptible or resistant were investigated. METHODS: The hyphal production of five C. albicans isolates under the action of antifungal agents was investigated by culturing yeast on growth medium and on hyphal induction medium. The genotypic characterization was carried out for 13 isolates of C. albicans using the random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) method. RESULTS: The dimorphism analysis showed that the hyphal formation was higher in resistant than in the susceptible isolates to both azoles. The RAPD-PCR method identified the formation of two different groups. In group A, four resistant and two susceptible isolates were clustered, and in group B, one resistant and six susceptible isolates were clustered. CONCLUSIONS: Considering that hyphal formation was higher in resistant isolates in the presence of azole drugs, we confirmed that the hyphal production is closely related to susceptibility to azoles. These drugs may affect the morphogenesis of C. albicans depending on their susceptibility to these drugs. In relation to RAPD-PCR, most resistant isolates classified in group A and susceptible isolates in group B demonstrated that this method presented a similar standard between the two groups, suggesting that by this technique, a strong correlation between genotypes and fluconazole resistant samples may be found. PMID- 22094709 TI - Diversity and distribution of the bioactive actinobacterial genus Salinispora from sponges along the Great Barrier Reef. AB - Isolates from the marine actinobacterial genus Salinispora were cultured from marine sponges collected from along the length of the Great Barrier Reef (GBR), Queensland, Australia. Strains of two species of Salinispora, Salinispora arenicola and "Salinispora pacifica", were isolated from GBR sponges Dercitus xanthus, Cinachyrella australiensis and Hyattella intestinalis. Phylogenetic analysis of the 16S rRNA gene sequences of representative strains, selected via BOX-PCR screening, identified previously unreported phylotypes of the species "S. pacifica". The classification of these microdiverse 16S rRNA groups was further confirmed by analysis of the ribonuclease P RNA (RNase P RNA) gene through both phylogenetic and secondary structure analysis. The use of RNase P RNA sequences combined with 16S rRNA sequences allowed distinction of six new intraspecies phylotypes of "S. pacifica" within the geographical area of the GBR alone. One of these new phylotypes possessed a localised regional distribution within the GBR. PMID- 22094710 TI - Macrophage folate receptor-beta (FR-beta) expression in auto-immune inflammatory rheumatic diseases: a forthcoming marker for cardiovascular risk? AB - In patients with systemic auto-immune inflammatory rheumatic diseases (AIIRD) like rheumatoid arthritis the prevalence of cardiovascular disease (CVD) is increased. In the pathogenesis of AIIRD and atherosclerosis many similarities can be found in the process underlying CVD. Accumulation of inflammatory cells, in particular macrophages at the site of inflammation producing inflammatory mediators serve as a prominent feature in both systemic inflammation and atherosclerosis. Two different subtypes of macrophages have been described in recent literature namely classically activated macrophages (M1) and alternatively activated macrophages (M2). Alternatively activated macrophages are characterized by low CD14 and high CD163 expression. Macrophages expressing CD14 (M1) have been identified within atherosclerotic plaques, whereas CD14 low macrophages are abundant in vessels without atherosclerosis. Depending on the environment and responses to different stimuli, macrophages in plaques can express diverse pro and anti-atherogenic functions. The balance of these different activation profiles influences atheroma evolution and outcome. Nowadays, influx of macrophages is recognized as a very important feature of the pathogenesis of plaque formation. Activated macrophages accumulate at the sites of inflammation and can therefore be exploited to better visualize inflammatory responses in atherosclerosis. Furthermore, activated (but not resting) macrophages possess a functionally active receptor for folate (FR-beta), but it is not completely clear which subtype of this activated macrophages expresses this receptor and whether the expression of FR-beta is restricted to only one of the macrophage subsets. Although future research needs to be done to investigate FR-beta expression and function within inflamed tissues, the expression of functional FR-beta on tissue macrophages likely occurs during activation. Therefore, expression of FR-beta on activated macrophages holds a promising potential for early diagnosis and better analysis of optimal treatment regiments of vascular diseases in association with systemic diseases. PMID- 22094711 TI - Impact of FDA guidance for developing diabetes drugs on trial design: from policy to practice. AB - In 2008, the US Food and Drug Administration (FDA) issued guidance requiring robust assessment of cardiovascular safety for all antidiabetic drugs to be licensed in the future. Here, we review the circumstances giving rise to the FDA guidance and describe the characteristics of clinical trials registered on ClinicalTrials.gov in the 36 months before and after the guidance was issued. We noted a doubling in the number of cardiovascular outcome trials registered and a sixfold increase in the median number of patients included in cardiovascular outcome trials in the latter 36 months. As the size and duration of follow-up for these trials increases, the clinical trials industry will need to adapt. The present review summarizes current attempts to streamline trial design and management to meet the requirements efficiently while adhering to the highest scientific standards. PMID- 22094712 TI - Histological presence of Helicobacter pylori bacteria in the trabeculum and iris of patients with primary open-angle glaucoma. AB - PURPOSE: To investigate the role of Helicobacter pylori in primary open-angle glaucoma (POAG) pathophysiology by detecting its presence in eye biopsies of POAG patients during trabeculectomy. PATIENTS AND METHODS: Fifty-one consecutive patients who underwent trabeculectomy for POAG not responsive to antiglaucoma therapy, and 35 consecutive anemic controls were examined for H. pylori presence mainly by gastric mucosa histology. In POAG patients, eye biopsies were also obtained and stained for H. pylori presence in situ. RESULTS: Forty-three of 51 (84.3%) POAG patients and 17 of 35 (48.6%) controls were tested H. pylori positive (p = 0.0004). In 5 H. pylori-positive POAG patients, H. pylori bacteria were identified in the trabeculum and iris specimens. CONCLUSION: For the first time, H. pylori bacteria have been detected histologically in eye biopsies of POAG patients. PMID- 22094713 TI - Upregulated miR-29b promotes neuronal cell death by inhibiting Bcl2L2 after ischemic brain injury. AB - It is increasingly clear that microRNAs (miRNAs) play an important role in controlling cell survival. However, the functional significance of miRNAs in ischemic brain injury remains poorly understood. In the present study, we assayed the expression levels of miR-29b after ischemic brain injury, and defined the target genes and biological functions of miR-29b. We found that the miR-29b levels were significantly increased in rat brain after transient middle cerebral artery occlusion and neurons after oxygen-glucose deprivation. Moreover, ectopic expression of miR-29b promoted neuronal cell death, whereas its repression decreased cell death. Furthermore, we verified that miR-29b directly targeted and inhibited Bcl2L2 gene expression, and then increased neuronal cell death. Importantly, Bcl2L2 overexpression rescued neuronal cell death induced by miR 29b. These results suggest an important role of miR-29b in regulating neuronal cell death, thus offering a new target for the development of therapeutic agents against ischemic brain injury. PMID- 22094714 TI - Role of APP for dendritic spine formation and stability. AB - The amyloid precursor protein (APP) is transported in high amounts to the presynaptic endings where its function is still unknown. Several studies indicate that lack of APP or its overexpression affects the number of dendritic spines, the postsynaptic compartment of excitatory synapses. Since synapse loss has been identified as one of the most important structural correlates of cognitive decline in Alzheimer's diseases (AD), the physiological function of APP at synapses, specifically at dendritic spines, has come into focus in AD research. This review intends to give an overview of the very controversial results on APP expression on dendritic spine number in the mouse brain. PMID- 22094715 TI - Eccentric exercise and delayed onset muscle soreness of the quadriceps induce adjustments in agonist-antagonist activity, which are dependent on the motor task. AB - This study investigates the effects of eccentric exercise and delayed onset muscle soreness (DOMS) of the quadriceps on agonist-antagonist activity during a range of motor tasks. Ten healthy volunteers (age, mean +/- SD, 24.9 +/- 3.2 years) performed maximum voluntary contractions (MVC) and explosive isometric contractions of the knee extensors followed by isometric contractions at 2.5, 5, 10, 15, 20, and 30% MVC at baseline, immediately after and 24 h after eccentric exercise of the quadriceps. During each task, force of the knee extensors and surface EMG of the vasti and hamstrings muscles were recorded concurrently. Rate of force development (RFD) was computed from the explosive isometric contraction, and the coefficient of variation of the force (CoV) signal was estimated from the submaximal contractions. Twenty-four hours after exercise, the subjects rated their perceived pain intensity as 4.1 +/- 1.2 (score out of 10). The maximum RFD and MVC of the knee extensors was reduced immediately post- and 24 h after eccentric exercise compared to baseline (average across both time points: 19.1 +/ 17.1% and 11.9 +/- 9.8% lower, respectively, P < 0.05). The CoV for force during the submaximal contractions was greater immediately after eccentric exercise (up to 66% higher than baseline, P < 0.001) and remained higher 24 h post-exercise during the presence of DOMS (P < 0.01). For the explosive and MVC tasks, the EMG amplitude of the vasti muscles decreased immediately after exercise and was accompanied by increased antagonist EMG for the explosive contraction only. On the contrary, reduced force steadiness was accompanied by a general increase in EMG amplitude of the vasti muscles and was accompanied by increased antagonist activity, but only at higher force levels (>15% MVC). This study shows that eccentric exercise and subsequent DOMS of the quadriceps reduce the maximal force, rate of force development and force steadiness of the knee extensors, and is accompanied by different adjustments of agonist and antagonist muscle activities. PMID- 22094716 TI - Emerging techniques in the minimally invasive treatment and management of thoracic spine tumors. AB - Over the past decade, the development and refinement of minimally invasive spine surgery techniques has lead to procedures with the potential to minimize iatrogenic and post-operative sequelae that may occur during the surgical treatment of various pathologies. In a similar manner, parallel advances in other current treatment technologies have led to the development of other minimally invasive treatments of spinal malignancies. These advances include percutaneous techniques for vertebral reconstruction, including vertebroplasty and kyphoplasty, the development of safe and effective spinal radiosurgery, and minimal-access spinal surgical procedures that allow surgeons to safely decompress and reconstruct the anterior spinal column. The advent of these new techniques has given modern practitioners treatment options in situations where they previously were limited by the potentially significant morbidities of the available techniques. Here, the authors discuss the application of current minimally invasive technologies in the treatment of malignancies of the thoracic spine, focusing on vertebral kyphoplasty, spinal radiosurgery, and minimally invasive spinal decompression techniques. The author's describe how these emerging treatment options are significantly expanding the options open to clinicians in the treatment of thoracic spinal column malignancies. Specific illustrative case examples are provided. The development of these techniques has the potential to improve clinical outcomes, limit surgical morbidity, and also improve the safety and efficiency of treatment pathways. PMID- 22094717 TI - A method to estimate the chronic health impact of air pollutants in U.S. residences. AB - BACKGROUND: Indoor air pollutants (IAPs) cause multiple health impacts. Prioritizing mitigation options that differentially affect individual pollutants and comparing IAPs with other environmental health hazards require a common metric of harm. OBJECTIVES: Our objective was to demonstrate a methodology to quantify and compare health impacts from IAPs. The methodology is needed to assess population health impacts of large-scale initiatives-including energy efficiency upgrades and ventilation standards-that affect indoor air quality (IAQ). METHODS: Available disease incidence and disease impact models for specific pollutant-disease combinations were synthesized with data on measured concentrations to estimate the chronic heath impact, in disability-adjusted life years (DALYs) lost, due to inhalation of a subset of IAPs in U.S. residences. Model results were compared with independent estimates of DALYs lost due to disease. RESULTS: Particulate matter <= 2.5 MUm in aerodynamic diameter (PM2.5), acrolein, and formaldehyde accounted for the vast majority of DALY losses caused by IAPs considered in this analysis, with impacts on par or greater than estimates for secondhand tobacco smoke and radon. Confidence intervals of DALYs lost derived from epidemiology-based response functions are tighter than those derived from toxicology-based, interspecies extrapolations. Statistics on disease incidence in the United States indicate that the upper-bound confidence interval for aggregate IAP harm is implausibly high. CONCLUSIONS: The approach demonstrated in this study may be used to assess regional and national initiatives that affect IAQ at the population level. Cumulative health impacts from inhalation in U.S. residences of the IAPs assessed in this study are estimated at 400-1,100 DALYs lost annually per 100,000 persons. PMID- 22094718 TI - Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer. AB - Crigler-Najjar type I (CNI) syndrome is a recessively inherited disorder characterized by severe unconjugated hyperbilirubinemia caused by uridine diphosphoglucuronosyltransferase 1A1 (UGT1A1) deficiency. The disease is lethal due to bilirubin-induced neurological damage unless phototherapy is applied from birth. However, treatment becomes less effective during growth, and liver transplantation is required. To investigate the pathophysiology of the disease and therapeutic approaches in mice, we generated a mouse model by introducing a premature stop codon in the UGT1a1 gene, which results in an inactive enzyme. Homozygous mutant mice developed severe jaundice soon after birth and died within 11 d, showing significant cerebellar alterations. To rescue neonatal lethality, newborns were injected with a single dose of adeno-associated viral vector 9 (AAV9) expressing the human UGT1A1. Gene therapy treatment completely rescued all AAV-treated mutant mice, accompanied by lower plasma bilirubin levels and normal brain histology and motor coordination. Our mouse model of CNI reproduces genetic and phenotypic features of the human disease. We have shown, for the first time, the full recovery of the lethal effects of neonatal hyperbilirubinemia. We believe that, besides gene-addition-based therapies, our mice could represent a very useful model to develop and test novel technologies based on gene correction by homologous recombination. PMID- 22094719 TI - Single- and two-phase flow in microfluidic porous media analogs based on Voronoi tessellation. AB - The objective of this study was to create a microfluidic model of complex porous media for studying single and multiphase flows. Most experimental porous media models consist of periodic geometries that lend themselves to comparison with well-developed theoretical predictions. However, many real porous media such as geological formations and biological tissues contain a degree of randomness and complexity at certain length scales that is not adequately represented in periodic geometries. To design an experimental tool to study these complex geometries, we created microfluidic models of random homogeneous and heterogeneous networks based on Voronoi tessellations. These networks consisted of approximately 600 grains separated by a highly connected network of channels with an overall porosity of 0.11-0.20. We found that introducing heterogeneities in the form of large cavities within the network changed the permeability in a way that cannot be predicted by the classical porosity-permeability relationship known as the Kozeny equation. The values of permeability found in experiments were in excellent agreement with those calculated from three-dimensional lattice Boltzmann simulations. In two-phase flow experiments of oil displacement with water we found that the wettability of channel walls determined the pattern of water invasion, while the network topology determined the residual oil saturation. The presence of cavities increased the microscopic sweeping efficiency in water-oil displacement. These results suggest that complex network topologies lead to fluid flow behavior that is difficult to predict based solely on porosity. The novelty of this approach is a unique geometry generation algorithm coupled with microfabrication techniques to produce pore scale models of stochastic homogeneous and heterogeneous porous media. The ability to perform and visualize multiphase flow experiments within these geometries will be useful in measuring the mechanism(s) of displacement within micro- and nanoscale pores. PMID- 22094721 TI - Successful demonstration of an efficient I(-)/(SeCN)2 redox mediator for dye sensitized solar cells. AB - A new I(-)/(SeCN)(2) redox mediator has favorable properties for dye-sensitized solar cells (DSCs) such as less visible light absorption, higher ionic conductivity, and downward shift of redox potential than I(-)/I(3)(-). It was then applied for DSCs towards increasing energy conversion efficiency, giving a new potential for improving performance. PMID- 22094720 TI - Comorbidity of conduct disorder symptoms and internalising problems in children: investigating a community and a clinical sample. AB - Previous studies have demonstrated that many children with conduct problems (CP) also show internalising psychopathology (IP). However, it remains unclear whether the presence of IP serves as a protective or risk factor for the severity and development of CP. The aim of the present study was to assess the prevalence and associations of comorbid IP in children with CP in a community and a clinical sample. Data from boys as well as girls with CP in the clinical range were obtained from a community sample (n = 1,160) and a clinical sample diagnosed with disruptive behaviour disorder (n = 193) from two European countries. In the community sample, information was obtained using the strengths and difficulties questionnaire, whereas in the clinical sample, the child behaviour checklist was used. Internalising disorders, according to ICD-10, were also assessed in the clinical sample. For both samples, age, gender, and impact of comorbid IP in the clinical range (above 90th percentile) for CP were explored. Results revealed that in both samples, participants with CP showed a high rate of comorbid IP (community sample: 35%; clinical sample: 78%). Participants with comorbid IP were more likely to experience social problems with peers. In the clinical sample, comorbid IP rated by the parents was more prevalent than internalising disorders according to ICD-10. Boys with CP and comorbid IP demonstrated a higher severity of externalising behaviour than boys without comorbid IP in the clinical sample. We concluded that in both samples, we found a high co-occurrence of CP and IP. Based on the idea that the co-occurrence of IP and CP in children and adolescents may potentially lead to increased antisocial behaviour, internalising psychopathology should be carefully investigated. Effective strategies and specific risk factors must be evaluated to treat comorbidity as early as possible in children with CP and IP. PMID- 22094722 TI - General condition of hikikomori (prolonged social withdrawal) in Japan: psychiatric diagnosis and outcome in mental health welfare centres. AB - BACKGROUND: The issue of hikikomori (prolonged social withdrawal) among Japanese youth has attracted attention from international experts. In previous research, the unique cultural and social factors of Japanese society have been the focus; however, in order to resolve the problem of hikikomori, individual mental health problems must be included. AIM: We examined the psychiatric background of individuals with hikikomori. METHODS: We recruited 337 individuals with hikikomori; 183 subjects who utilized the centres were designated as the help seeking group. We examined the multi-axial psychiatric diagnosis based on the DSM IV-TR, treatment policies and treatment outcomes. We also examined 154 subjects who did not utilize the centers (non-help-seeking group). RESULTS: Most of the subjects in the utilization group were classified into one of the diagnostic categories. Forty-nine (33.3%) subjects were diagnosed with schizophrenia, mood disorders or anxiety disorders, and this group needed pharmacotherapy. Other subjects were diagnosed with personality disorders or pervasive developmental disorders, and they mainly needed psycho-social support. The Global Assessment of Functioning (GAF) scores of the non-help-seeking group were significantly lower than the GAF scores of those who used treatments. CONCLUSION: Most hikikomori cases can be diagnosed using current diagnostic criteria. Individuals with hikikomori are much worse if they do not seek help. PMID- 22094723 TI - The best places for miniscrews. PMID- 22094724 TI - Anatomical guidelines for miniscrew insertion: palatal sites. PMID- 22094725 TI - The insignia system of customized orthodontics. PMID- 22094726 TI - A modified dental probe for orthodontic use. PMID- 22094727 TI - Adjusting force vectors during maxillary retraction with miniscrew anchorage. PMID- 22094728 TI - Bonding a lingual retainer to denture crowns. PMID- 22094729 TI - The Forsus Fatigue Resistant Device as a fixed functional appliance. PMID- 22094730 TI - Vertebrate neural stem cell segmentation, tracking and lineaging with validation and editing. AB - This protocol and the accompanying software program called LEVER (lineage editing and validation) enable quantitative automated analysis of phase-contrast time lapse images of cultured neural stem cells. Images are captured at 5-min intervals over a period of 5-15 d as the cells proliferate and differentiate. LEVER automatically segments, tracks and generates lineage trees of the stem cells from the image sequence. In addition to generating lineage trees capturing the population dynamics of clonal development, LEVER extracts quantitative phenotypic measurements of cell location, shape, movement and size. When available, the system can include biomolecular markers imaged using fluorescence. It then displays the results to the user for highly efficient inspection and editing to correct any errors in the segmentation, tracking or lineaging. To enable high-throughput inspection, LEVER incorporates features for rapid identification of errors and for learning from user-supplied corrections to automatically identify and correct related errors. PMID- 22094731 TI - Determining the number of specific proteins in cellular compartments by quantitative microscopy. AB - This protocol describes a method for determining both the average number and variance of proteins, in the few to tens of copies, in isolated cellular compartments such as organelles and protein complexes. Other currently available protein quantification techniques either provide an average number, but lack information on the variance, or they are not suitable for reliably counting proteins present in the few to tens of copies. This protocol entails labeling of the cellular compartment with fluorescent primary-secondary antibody complexes, total internal reflection fluorescence microscopic imaging of the cellular compartment, digital image analysis and deconvolution of the fluorescence intensity data. A minimum of 2.5 d is required to complete the labeling, imaging and analysis of a set of samples. As an illustrative example, we describe in detail the procedure used to determine the copy number of proteins in synaptic vesicles. The same procedure can be applied to other organelles or signaling complexes. PMID- 22094732 TI - Identifying microbial fitness determinants by insertion sequencing using genome wide transposon mutant libraries. AB - Insertion sequencing (INSeq) is a method for determining the insertion site and relative abundance of large numbers of transposon mutants in a mixed population of isogenic mutants of a sequenced microbial species. INSeq is based on a modified mariner transposon containing MmeI sites at its ends, allowing cleavage at chromosomal sites 16-17 bp from the inserted transposon. Genomic regions adjacent to the transposons are amplified by linear PCR with a biotinylated primer. Products are bound to magnetic beads, digested with MmeI and barcoded with sample-specific linkers appended to each restriction fragment. After limited PCR amplification, fragments are sequenced using a high-throughput instrument. The sequence of each read can be used to map the location of a transposon in the genome. Read count measures the relative abundance of that mutant in the population. Solid-phase library preparation makes this protocol rapid (18 h), easy to scale up, amenable to automation and useful for a variety of samples. A protocol for characterizing libraries of transposon mutant strains clonally arrayed in a multiwell format is provided. PMID- 22094733 TI - Prospective isolation of adult neural stem cells from the mouse subependymal zone. AB - Neural stem cells (NSCs) have the remarkable capacity to self-renew and the lifelong ability to generate neurons in the adult mammalian brain. However, the molecular and cellular mechanisms contributing to these behaviors are still not understood. Now that prospective isolation of the NSCs has become feasible, these mechanisms can be studied. Here we describe a protocol for the efficient isolation of adult NSCs, by the application of a dual-labeling strategy on the basis of their glial identity and ciliated nature. The cells are isolated from the lateral ventricular subependymal zone (SEZ) of adult hGFAP-eGFP (human glial fibrillary acidic protein-enhanced green fluorescent protein) transgenic mice by fluorescence-activated cell sorting. Staining against prominin1 (CD133) allows the isolation of the NSCs (hGFAP-eGFP(+)/prominin1(+)), which can be further subdivided by labeling with the fluorescent epidermal growth factor. This protocol, which can be completed in 7 h, allows the assessment of quantitative changes in SEZ NSCs and the examination of their molecular and functional characteristics. PMID- 22094734 TI - Backbone chemical shifts assignments, secondary structure, and ligand binding of a family GH-19 chitinase from moss, Bryum coronatum. AB - Family GH19 chitinases have been recognized as important in the plant defense against fungal pathogens. However, their substrate-recognition mechanism is still unknown. We report here the first resonance assignment of NMR spectrum of a GH19 chitinase from moss, Bryum coronatum (BcChi-A). The backbone signals were nearly completely assigned, and the secondary structure was estimated based on the chemical shift values. The addition of the chitin dimer to the enzyme solution perturbed the chemical shifts of HSQC resonances of the amino acid residues forming the putative substrate-binding cleft. Further NMR analysis of the ligand binding to BcChi-A will improve understanding of the substrate-recognition mechanism of GH-19 enzymes. PMID- 22094735 TI - Acellular dermis-assisted prosthetic breast reconstruction: a systematic and critical review of efficacy and associated morbidity. AB - BACKGROUND: The use of acellular dermal matrix to assist in two-stage expander/implant breast reconstruction has increased over recent years. However, there are questions regarding the potential for increased morbidity when using these techniques relative to standard submuscular coverage techniques. This systematic review combines published data comparing the techniques, to compare morbidity and advantages of acellular dermal matrix relative to standard submuscular coverage techniques. METHODS: An English language literature search was performed to find articles reporting outcomes of two-stage expander/implant reconstruction using acellular dermal matrix. The outcome categories analyzed were patient/treatment demographics, tissue expander characteristics, and complications. RESULTS: Nine articles met inclusion criteria for this analysis. Six of these were matched cohort studies comparing outcomes of acellular dermal matrix techniques to standard submuscular techniques. The remaining three were case series of acellular dermal matrix techniques. The only difference found in complications was a higher rate of seroma for the acellular dermal matrix group (4.3 percent versus 8.4 percent, p = 0.03). Despite this, both groups illustrated similar rates of infection leading to explantation (3.2 percent for submuscular and 3.4 percent for acellular dermal matrix, p = 0.18). In addition, acellular dermal matrix techniques illustrated greater intraoperative fill volumes and consistently fewer fills required to reach expander capacity. CONCLUSIONS: The use of acellular dermal matrix in two-stage expander/implant reconstruction offers a safety profile similar to that of standard submuscular techniques. Both techniques have shown similar rates of infection ultimately requiring explantation. In addition, acellular dermal matrix offers the advantage of a more rapid reconstruction with less need for manipulation of the prosthetic through filling. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 22094736 TI - Retrospective review of 331 consecutive immediate single-stage implant reconstructions with acellular dermal matrix: indications, complications, trends, and costs. AB - BACKGROUND: Immediate single-stage direct-to-implant breast reconstruction with acellular dermal matrix optimizes aesthetics by preserving the mastectomy skin envelope. The authors report trends, early complications, and costs. METHODS: A retrospective review of three surgeons' experience was performed for immediate single-stage implant reconstruction with acellular dermal matrix and tissue expander reconstruction without it at Massachusetts General Hospital. RESULTS: Two hundred eleven patients had 331 direct-to-implant reconstructions using AlloDerm following nipple-sparing (n = 66) or skin-sparing (n = 265) mastectomy for cancer (n = 216) or prophylaxis (n = 115). The number of single-stage implant reconstructions increased from seven in 2006 to 116 in 2009. The percentage performed for prophylaxis increased from 29 percent to 41 percent. Fifty-one patients underwent preoperative (n = 33) or postoperative (n = 18) irradiation. Total complications included 10 infections (3.0 percent), five seromas (1.5 percent), four hematomas (1.2 percent), and 30 reconstructions (9.1 percent), with skin necrosis leading to five implant losses (1.5 percent). Tissue expander reconstruction without AlloDerm had a similar total complication rate (158 reconstructions) (p = 0.18), including nine infections (5.7 percent), three seromas (1.9 percent), three hematomas (1.9 percent), and 16 reconstructions (10.1 percent), with skin necrosis leading to 11 implant losses (7.0 percent). A higher complication rate occurred in the surgeons' combined first year performing single-stage implant reconstruction (21.4 percent) compared with subsequent years (10.9 percent) (p < 0.02) and in one- or two-stage reconstruction patients undergoing irradiation (p = 0.005). There was no significant difference in total overall costs (p = 0.8). CONCLUSIONS: Immediate single-stage implant reconstruction using acellular dermal matrix offers a cost-effective reconstruction with a low complication rate. This may be the procedure of choice in select patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 22094737 TI - Increasing age impairs outcomes in breast reduction surgery. AB - BACKGROUND: Although multiple breast reduction outcomes studies have been performed, none has specifically identified the impact of advanced age. The authors aimed to study the impact of age on breast reduction outcome. METHODS: Medical records for all patients billed for Current Procedural Terminology code 19318 over the past 10 years (1999 to 2009) at a large academic institution were analyzed under an institutional review board-approved protocol. A total of 1192 consecutive patients underwent 2156 reduction mammaplasties performed by 17 plastic surgeons over a 10-year period. Breast reduction techniques included inferior pedicle/Wise pattern in 1250 patients (58.9 percent), medial pedicle/Wise pattern in 360 (16.9 percent), superior pedicle/nipple graft in 305 (14.4 percent), superior pedicle/vertical pattern in 206 (9.7 percent), and liposuction in three (0.14 percent). The average patient age was 36 years. Age groups were divided into younger than 40 years, 40 to 50 years, and older than 50 years. Multiple logistic regression analysis was performed to identify significant relationships. RESULTS: Women older than 50 years more likely experienced infection (odds ratio, 2.7; p = 0.003), with trends toward wound healing problems (odds ratio, 1.6; p = 0.09) and reoperative wound debridement (odds ratio, 5.1; p = 0.07). There was a trend toward infection in women aged 40 to 50 years (odds ratio, 1.7; p = 0.08). Advanced age did not exacerbate fat necrosis or seroma development. CONCLUSIONS: Age older than 50 years impairs breast reduction outcomes, particularly infection, and may negatively impact wound healing. Hormonal deficiency may partially account for this finding. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV. PMID- 22094738 TI - Discussion: increasing age impairs outcomes in breast reduction surgery. PMID- 22094739 TI - Tissue-engineered breast reconstruction: bridging the gap toward large-volume tissue engineering in humans. AB - BACKGROUND: Use of autologous tissue is ideal in breast reconstruction; however, insufficient donor tissue and surgical and donor-site morbidity all limit its use. Tissue engineering could provide replacement tissue, but only if vascularization of large tissue volumes is achievable. The authors sought to upscale their small-animal adipose tissue-engineering models to produce large volumes of tissue in a large animal (i.e., pig). METHODS: Bilateral large-volume (78.5 ml) chambers were inserted subcutaneously in the groin enclosing a fat flap (5 ml) based on the superficial circumflex iliac pedicle for 6 (n = 4), 12 (n = 1), and 22 weeks (n = 2). Right chambers included a poly(L-lactide-co-glycolide) sponge. Other pedicle configurations, including a vascular pedicle alone (n = 2) or in combination with muscle (n = 2) or a free fat graft (n = 2), were investigated in preliminary studies. Serial assessment of tissue growth and vascularization by magnetic resonance imaging was undertaken during growth and correlated with quantitative histomorphometry at chamber removal. RESULTS: All chambers filled with new tissue by 6 weeks, vascularized by the arteriovenous pedicle. In the fat flap chambers, the initial 5 ml of fat expanded to 25.9 +/- 2.4, 39.4 +/- 3.9, and 56.5 ml (by magnetic resonance imaging) at 6, 12, and 22 weeks, respectively. Adipose tissue volume was maintained up to 22 weeks after chamber removal (n = 2), including one where the specimen was transferred on its pedicle to an adjacent submammary pocket. CONCLUSION: The first clinically relevant volumes of tissue for in situ and remote breast reconstruction have been formed with implications for scaling of existing tissue-engineering models into human trials. PMID- 22094740 TI - Dental implant outcome after primary implantation into double-barreled fibula osteoseptocutaneous free flap-reconstructed mandible. AB - BACKGROUND: Functional and aesthetic mandibular reconstruction can be achieved in a single operation by means of a double-barreled fibula osteoseptocutaneous free flap with dental implants loaded simultaneously into the upper barrel. The aim of this study was to evaluate the quality and result of such reconstruction. METHODS: From 2005 to 2007, 10 patients underwent segmental mandibular defect reconstructions with double-barreled fibula osteoseptocutaneous flaps and simultaneous dental implantations. Implant marginal bone loss, clinical mucosal changes, marginal plaque indices, bleeding on probing, and pocket probe depth were evaluated at an average of 22.2 months after implant functional loading. RESULTS: Ten patients with a total of 25 osseointegrated implants were evaluated. The mean implant marginal bone loss was 0.18 +/- 0.18 mm (range, 0 to 0.6 mm) at the mesial surfaces and 0.25 +/- 0.2 mm (range, 0 to 0.6 mm) at the distal surfaces. Probing pocket depth was shallower for implants protected by palatal mucosal grafts (2.56 +/- 0.54 mm) than by skin flaps (3.50 +/- 0.90 mm) (p < 0.05). There was a significant difference in marginal bone loss between palatal mucosal grafts (0.11 +/- 0.09 mm) and skin flaps (0.29 +/- 0.23 mm) (p < 0.05). Bleeding on probing was more prominent when pocket depth exceeded 5 mm and occurred more frequently in skin flap-protected than in keratinized mucosa graft protected implants. CONCLUSIONS: The one-stage combined surgical method is safe and reliable. Both oral function and mandible contour were good. Firmly attached gingiva-like palatal mucosal grafts prevent periimplant soft-tissue inflammation and facilitate maintenance of oral hygiene. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 22094741 TI - The incidence of venous thromboembolism in postoperative plastic and reconstructive surgery patients with chronic spinal cord injury. AB - BACKGROUND: The purpose of this study was to investigate the incidence of postoperative venous thromboembolism in chronic spinal cord injury patients undergoing plastic and reconstructive surgery. Previous studies show a venous thromboembolism incidence of 9.3 percent; however, based on anecdotal evidence, the authors hypothesize that the incidence is actually much lower. As postoperative venous thromboembolism prophylaxis is becoming mandated by the Surgical Care Improvement Project, more data are necessary so that recommendations for chronic spinal cord injury patients can be given. METHODS: A retrospective chart review was undertaken using electronic medical records from a Veterans Affairs hospital from 2004 through 2009 in which the perioperative course of the chronic spinal cord injury cohort was evaluated for the primary endpoint of venous thromboembolism evolution. The Pearson correlation was used for statistical analysis. RESULTS: Of the 415 operative cases evaluated, 155 cases were excluded secondary to operative time under 1 hour, use of mechanical or chemical venous thromboembolism prophylaxis, unknown operative time, or unknown prophylaxis use. Of the 260 cases evaluated without venous thromboembolism prophylaxis, there were no cases where venous thromboembolism developed within a 2-month postoperative time period. CONCLUSIONS: Postoperative venous thromboembolism is a common surgical complication with significant morbidity and mortality. This study demonstrates that in the chronic spinal cord injury patient cohort, the incidence of postoperative venous thromboembolism evolution is extremely low and that a benefit from perioperative mechanical or chemical prophylaxis is not evidence based. Further prospective studies are required to fully elucidate the true venous thromboembolism incidence in these patients and give recommendations on this issue. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 22094742 TI - Panniculectomy in preparation for renal transplantation: a new indication for an old procedure to reduce renal transplantation-associated wound complications. AB - End-stage renal disease patients who have lost a significant amount of weight are increasingly being evaluated for kidney transplantation. An abdominal panniculus, almost uniformly observed, creates an area predisposed to wound complications. Consequently, a panniculus may limit a patient's candidacy for transplantation. The authors describe their preliminary experience utilizing panniculectomy as a prophylactic procedure to reduce wound complications following kidney transplantation in patients whose panniculus would exclude them from renal transplantion. A single-institution chart review was conducted of nine patients with end-stage renal disease who underwent a panniculectomy in preparation for transplantation. Clinical outcomes and complications were reviewed. The nine patients included three men and six women with a mean age of 54.5 years and a mean body mass index of 28.3 kg/m. Four patients had diabetes. All patients underwent an uncomplicated panniculectomy, with a mean resected weight of 3.0 kg, and a mean length of hospital stay of 1.75 days. No one required blood transfusions. All patients were followed postoperatively for 3 months. Complications included an abscess and a skin dehiscence treated with local wound care. After recovery, patients were referred to the transplant center for re evaluation for kidney transplantation. Thus far, four of these nine patients have undergone transplantation. This case series suggests that panniculectomy can be performed safely in patients with end-stage renal disease. Furthermore, panniculectomy gives these otherwise unsuitable kidney transplant candidates access to a life-saving operation. PMID- 22094743 TI - Efficient design of split anterolateral thigh flap in extremity reconstruction. AB - BACKGROUND: Irregularly shaped and three-dimensional soft-tissue defects in the extremities are difficult to cover precisely and efficiently. One strategy is to use the anterolateral thigh flap with two perforators and split the flap into two subunits based on separate perforators. The subunits can be rearranged into various geometric configurations to cover defects with nonelliptical shapes. Such a strategy emphasizes harvesting an elliptical anterolateral thigh flap with a narrower width to allow for primary closure in most cases. This avoids the need for skin grafting and reduces donor-site morbidity. METHODS: From 2002 to 2010, 15 patients with upper and lower limb defects were treated with split anterolateral thigh flaps. There were nine male patients and six female patients. The mean age of the patients was 40.6 years (range, 18 to 64 years). The shape of each defect was classified as arrow-shape, hourglass-shape, triangular, or three dimensional. RESULTS: All split flaps (n = 31) survived without vascular problems. Two split flaps demonstrated margin necrosis without critical structure exposure. Only one donor site needed skin grafting. All other donor sites were closed primarily. CONCLUSIONS: The split anterolateral thigh flap is an effective strategy for covering irregular and three-dimensional defects in the extremities. It allows efficient use of the harvested flap and minimizes trimming and discarding unused flap parts. This decreases the area of skin graft needed for donor-site coverage and may even be able to achieve primary closure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 22094744 TI - Dupuytren's disease in the Hispanic population: a 10-year retrospective review. AB - BACKGROUND: Dupuytren's disease is a common benign fibroproliferative disorder of the hand. Epidemiologic studies have reported significant variation in disease prevalence among races, focusing primarily on those of northern European descent. In contrast, Dupuytren's disease in the Hispanic population has received little attention. Thus, in this study, the authors aimed to determine the prevalence and operative rate of Dupuytren's disease in the Hispanic, black, white, Asian, Native American, and other races and to characterize the disease presentation in Hispanics who required surgical treatment. METHODS: A retrospective review was conducted to identify the racial distribution of Dupuytren's disease patients seen at Bellevue Hospital between July of 2000 and August of 2010. In Hispanic patients requiring surgical treatment for their disease, data were collected on the following parameters: age, sex, ethnicity, hand dominance, hand affected, and digits operated on. Epidemiologic factors including smoking, alcoholism, diabetes mellitus, hypercholesterolemia, epilepsy, and hypertension were also evaluated. RESULTS: Dupuytren's disease prevalence was found to be 533 per 100,000 in Hispanics. Of these patients, 1.8 percent required surgical treatment, and this group was characterized by the following comorbidities: smoking (57.1 percent), hypertension (57.1 percent), alcoholism (52.4 percent), diabetes mellitus (47.6 percent), and hypercholesterolemia (19.0 percent). CONCLUSIONS: The authors' results indicate that Dupuytren's disease is more prevalent in the Hispanic population than previously reported. Although the epidemiologic factors identified in Hispanics with Dupuytren's disease are similar to those in other races investigated, there are important differences with respect to clinical presentation and surgical treatment. PMID- 22094745 TI - Anatomical relationship of Roos' type 3 band and the T1 nerve root. AB - BACKGROUND: The most common clinical presentation of thoracic outlet syndrome stems from compression of the lower trunk of the brachial plexus or ulnar nerve. A plethora of anatomical variations have been implicated in the cause of thoracic outlet syndrome. Roos' identification and classification of scalene muscle and fibrous bands have added an additional dimension to understanding its cause and subsequent treatment. Understanding the anatomy and relationship of this band with the lower trunk of the brachial plexus is of paramount importance. METHODS: As part of the authors' long-term study of the type 3 band in relation to the brachial plexus, 70 embalmed cadavers were dissected to yield 100 first thoracic ribs. Fibrous bands, when present, were studied in relation to the brachial plexus. RESULTS: A fibrous band consistent with Roos' type 3 was identified and found to occur in 35 percent of first ribs and 41 percent of cadavers. The mean size was 3.45 * 0.27 cm. Origins and insertions are described. Contrary to Roos' own description, however, the authors observed that Roos' type 3 band was anterior to the T1 nerve root, creating a tunnel through which the T1 nerve root must pass before joining the C8 nerve root. CONCLUSIONS: The authors believe that the type 3 band, when present, can create a tunnel that compresses the T1 nerve root against the first rib, potentially predisposing susceptible individuals to thoracic outlet syndrome. Clinical studies are needed to determine whether correlations between type 3 bands and thoracic outlet syndrome exist. PMID- 22094746 TI - Limited reduction cranioplasty for the treatment of hydrocephalic macrocephaly. AB - BACKGROUND: Hydrocephalic macrocephaly, occurring despite adequate cerebrospinal fluid shunting, is rare, and most publications advocate near-total cranial vault reduction procedures. The authors reviewed our series of limited reductions (designed to minimize complications while still providing functional benefits) to evaluate outcomes. METHODS: All patients undergoing posterior reduction cranioplasties were retrospectively reviewed for outcomes, including operative data, length of stay, preoperative and postoperative anthropometrics, and complications. In addition, preoperative and postoperative motor function was assessed using a novel scale. These data were then compared with published series. RESULTS: Ten patients (five male, five female) underwent reduction cranioplasties for macrocephaly at an average age of 17.9 months (range, 6 to 53 months) and were followed for an average of 41.5 months. The mean operative time was 4.9 hours (range, 4.3 to 6.5 hours), estimated blood loss was 530 ml (range, 200 to 1500 ml), and 78 percent received blood transfusions. The average length of hospitalization was 2.6 days. Three patients experienced complications, including one shunt revision. The mean functional assessment scores increased from 2.3 to 3.9 (p = 0.022), with all patients able to support their heads postoperatively. CONCLUSIONS: Use of a limited cranioplasty technique was associated with a hospitalization that was over 7 days shorter than has been reported in the literature for total cranial vault reductions and with a much lower shunt revision rate. Measurable improvements in motor function and subjective benefits in appearance were noted, despite a more limited reduction. Surgeons faced with this unusual condition may wish to consider performing this smaller procedure. PMID- 22094747 TI - A retrospective photometric study of 82 published reports of mastopexy and breast reduction. AB - BACKGROUND: Numerous publications claim to improve breast projection and upper pole fullness after mastopexy or breast reduction. Fascial sutures and "autoaugmentation" with local flaps are advocated. However, there is no objective evidence that these efforts are effective. The author has proposed a measuring system to quantitate results. Not only is this system useful for assessing one's own results, but it may also be used to assess and compare results in published studies. METHODS: Eighty-two international publications on mastopexies and breast reductions were analyzed. The studies were grouped by technique: inverted-T (superior/medial, central, and inferior pedicles), vertical, periareolar, inframammary, lateral, and "other." Measurements were made using the definitions and terminology reported separately and included breast projection, upper pole projection, lower pole level, nipple level, breast convexity, breast parenchymal ratio, and lower pole ratio. Areola shape was assessed. RESULTS: Breast projection and upper pole projection were not increased significantly by any of the mastopexy/reduction procedures or by the use of fascial sutures or autoaugmentation techniques. Nipple overelevation was common (41.9 percent). The incidence of the teardrop areola deformity (53.8 percent) was significantly higher (p < 0.001) in patients treated with the open technique of nipple placement. There was no significant difference in results when compared by follow up times, resection weights, year of publication, or geographic region. CONCLUSIONS: Existing mastopexy/reduction techniques do not significantly increase breast projection or upper pole projection. Fascial sutures and autoaugmentation techniques are ineffective. Nipple overelevation and the teardrop areola deformity are common problems and should be avoided. PMID- 22094748 TI - So you want to be like Leonardo da Vinci or Michelangelo? Which one are you? PMID- 22094749 TI - How the evidence has changed my practice. PMID- 22094755 TI - Perfusion-related complications are similar for DIEP and muscle-sparing free TRAM flaps harvested on medial or lateral deep inferior epigastric Artery branch perforators for breast reconstruction. AB - BACKGROUND: Anatomical studies suggest that the deep inferior epigastric artery (DIEA) medial branch perfuses more tissue across the midline than the lateral branch. The authors hypothesized that unilateral deep inferior epigastric perforator (DIEP) and muscle-sparing free transverse rectus abdominis musculocutaneous (TRAM) flaps based on medial branch perforators would have fewer perfusion-related complications. METHODS: The authors evaluated consecutive DIEP or muscle-sparing TRAM free flaps definitively harvested from a single DIEA branch. Flaps were grouped by tissue volume (hemiflaps, cross-midline flaps, or total flaps). Primary outcome measures were fat necrosis and partial flap necrosis. Logistic regression was used to evaluate the association between patient and reconstruction characteristics and outcomes. RESULTS: There were 228 patients, with 120 medial (52.6 percent) and 108 lateral (47.4 percent) branch flaps. Mean follow-up was 33.2 months. Cross-midline flaps (79.8 percent) were the most common design. Medial and lateral branch flaps had similar rates of fat necrosis (8.3 percent and 13.0 percent, respectively; p = 0.26) and partial flap necrosis (3.3 percent and 2.8 percent, respectively; p = 1.0). There was no difference in the incidence of fat necrosis between DIEP and muscle-sparing free TRAM flaps (10.2 percent and 11.3 percent, respectively; p = 0.81) or in partial necrosis (3.2 percent and 2.8 percent, respectively; p = 1.0). Medial and lateral branch flap perfusion-related complications were also similar among the flap volume classifications. CONCLUSIONS: The authors suggest that surgeons base their decisions regarding DIEA branch harvest on the clinical assessment of perforator perfusion quality rather than relying on the theoretical benefit of medial branch perforator harvest. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 22094756 TI - Discussion: perfusion-related complications are similar for DIEP and muscle sparing free TRAM flaps harvested on medial or lateral deep inferior epigastric artery branch perforators for breast reconstruction. PMID- 22094757 TI - Simultaneous scarless contralateral breast augmentation during unilateral breast reconstruction using bilateral differentially split DIEP flaps. AB - BACKGROUND: : Simultaneous contralateral augmentation is performed with unilateral breast reconstruction to achieve pleasing and symmetric breast mounds. This prospective study investigated the outcome of simultaneous scarless contralateral augmentation with unilateral breast reconstruction using bilateral differentially split deep inferior epigastric perforator (DIEP) flaps. METHODS: : Between August of 2009 and May of 2010, six patients with a mean age of 46.2 +/- 7 years underwent unilateral breast reconstruction and simultaneous contralateral augmentation using bilateral differentially split DIEP flaps. The ipsilateral internal mammary vessels served as the recipient vessels for the reconstruction split flap. The pedicle of the augmentation split flap was anastomosed to that of the reconstruction split flap in a flow-through manner. The augmentation split flap was inset through the midline with endoscopic assistance. The Modified BREAST-Q questionnaire was administered preoperatively and at the 1- and 3-month follow-up visits. RESULTS: : All flaps survived, giving a success rate of 100 percent. One reconstruction split flap required reexploration and was salvaged successfully. Mean flap weights used for reconstruction and augmentation were 410 +/- 145 and 192 +/- 58 g, respectively. At a mean follow-up of 12.7 +/- 3.6 months, all patients were satisfied with the outcome of both reconstructed and augmented breast mounds. There were statistical improvements in breast satisfaction (p = 0.004), psychosocial function (p = 0.000), and sexual well being (p = 0.004) postoperatively, as assessed by the Modified BREAST-Q. CONCLUSION: : Simultaneous scarless contralateral breast augmentation can be performed safely during unilateral breast reconstruction using bilateral differentially split DIEP flaps with satisfactory outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: : Therapeutic, IV. PMID- 22094758 TI - Discussion: simultaneous scarless contralateral breast augmentation during unilateral breast reconstruction using bilateral differentially split DIEP flaps. PMID- 22094759 TI - Transverse upper gracilis flap as an alternative to abdominal tissue breast reconstruction: technique and modifications. AB - BACKGROUND: The inner thigh skin and fat based on the transverse upper gracilis musculocutaneous flap blood supply provide an autologous donor area with qualities favorable to microvascular breast reconstruction. The flap can be shaped to mimic a mastectomy specimen, providing excellent contour and projection, and has a consistent blood supply. The characteristics and skin color of the flap allow for immediate nipple-areola complex reconstruction in skin sparing mastectomy. METHODS: From 2004 to 2007, the authors performed 32 free inner thigh flap microvascular breast reconstructions after mastectomy for breast cancer in 20 patients, in both delayed and immediate settings. RESULTS: All flaps survived without any soft-tissue loss or fat necrosis. Complications were a single take-back for venous thrombosis with salvage, donor-site skin breakdown in eight flaps, and five seromas. There was no functional loss at the donor site, and all patients resumed normal activity. CONCLUSIONS: Transverse upper gracilis musculocutaneous flap microvascular breast reconstruction is an excellent option for patients who desire autologous reconstruction and who do not have adequate abdominal donor tissue or who do not desire abdominal scarring. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 22094760 TI - Trials and tribulations with the inferior gluteal artery perforator flap in autologous breast reconstruction. AB - BACKGROUND: Perforator free flaps from the buttock serve as an alternative to abdominally based flaps in autologous breast reconstruction. Microsurgeons often opt to harvest tissue from the gluteal donor site because of a lack of abdominal volume and/or quality. The authors examined the experience of a single surgeon with the inferior gluteal artery perforator (IGAP) flap and provide a quantitative outcomes comparison with the deep inferior epigastric perforator (DIEP) flap. METHODS: A retrospective review was performed of patients who underwent IGAP flap surgery for autologous breast reconstruction from August of 2005 to October of 2010 performed by a single surgeon (J.M.S.). RESULTS: Thirty one inferior gluteal artery perforator flaps were performed on 24 patients. Mean follow-up time was 24.4 months (range, 6 to 65 months). The total flap loss rate was 6.5 percent, and the take-back rate was 13 percent (salvage rate, 75 percent). Vascular complication rates were as follows: intraoperative arterial thrombosis, 13 percent; intraoperative venous thrombosis, 3 percent; delayed arterial thrombosis, 3 percent; and delayed venous thrombosis, 13 percent. Nineteen percent of patients had sensory complaints at the donor site that persisted beyond 3 months postoperatively. In comparison to the DIEP flap, IGAP flaps had a higher rate of intraoperative arterial thrombosis (13 percent versus 2.6 percent, p = 0.024) and delayed venous thrombosis (13 percent versus 1.5 percent, p = 0.008). CONCLUSIONS: Review of the IGAP flap reveals some shortcomings of this flap even in the hands of an experienced microsurgeon. Surgeons should be aware of the difficulties and limitations when choosing this flap for reconstruction. PMID- 22094761 TI - Discussion: trials and tribulations with the inferior gluteal artery perforator flap in autologous breast reconstruction. PMID- 22094762 TI - The lateral chest wall: a separate aesthetic unit in breast surgery. AB - BACKGROUND: The lateral chest wall is an aesthetic unit often overlooked in breast surgery. Abnormalities are often seen in candidates for aesthetic and reconstructive breast surgery and in the massive weight loss population. Preoperative evaluation of the lateral chest wall is necessary to address this area properly. These deformities are intimately associated with the final outcome of any breast operation. METHODS: To better define deformities of the lateral chest wall, a series of 522 patients who had aesthetic or reconstructive breast surgery was reviewed retrospectively. The preoperative and postoperative photographs were evaluated by two surgeons independently. Any surgical approaches used to correct lateral chest wall deformities were documented. RESULTS: In evaluating the lateral chest wall, the authors identified three subunit areas that need to be addressed to maximize aesthetic result: the axilla, the lateral breast, and the chest wall. Deficiency and excess of skin and fat contribute to any deformities in this region; deficiency or excess was found in 39 percent of patients. These deformities, when identified, were surgically addressed in 40 percent of patients, as management strategies included transfer of autologous tissue, fat injection, liposuction, or direct excision. CONCLUSIONS: Lateral chest wall deformities are often found among breast surgery candidates and can affect the final outcome. This area should be treated as a separate aesthetic unit from the breast. Patients with deficiency or excess should be counseled appropriately, as proper treatment may require procedures in addition to the primary breast procedure. The classification system presented can serve as a guideline for management of deformities in this region. PMID- 22094763 TI - Discussion: the lateral chest wall: a separate aesthetic unit in breast surgery. PMID- 22094764 TI - The significance of latissimus dorsi flap innervation in delayed breast reconstruction: a prospective randomized study-magnetic resonance imaging and histologic findings. AB - BACKGROUND: It is controversial whether surgical denervation of the thoracodorsal nerve should be performed in breast reconstruction with a myocutaneous latissimus dorsi flap. Denervation may prevent discomforting symptoms caused by muscle contraction, but the flap may also lose significant volume. The authors prospectively evaluated the influence of latissimus dorsi flap innervation on the latissimus dorsi muscle structure in delayed breast reconstruction. METHODS: Between 2007 and 2008, 28 breast reconstructions were performed and divided randomly into the denervation group (surgical denervation by excision of 1 cm of thoracodorsal nerve, n = 14) and the intact group (thoracodorsal nerve saved intact, n = 14). Muscle biopsy specimens were taken during the operation and 6 months after reconstruction. Histologic (hematoxylin and eosin), immunohistochemical (human developmental, neonatal, slow, and fast myosin heavy chains), and morphometric analyses were performed. Magnetic resonance imaging of the breasts was performed 1 and 12 months after surgery. RESULTS: There was a significant decrease in type I and type II myofiber diameters from 0 to 6 months in both groups. Denervation caused more significant atrophy than disuse alone. However, there was no significant difference in flap thickness between groups that can be explained by more pronounced fatty tissue infiltration in the denervation group. CONCLUSIONS: The authors' data suggest that the volume and consistency of the flap remain more or less the same, regardless of whether the thoracodorsal nerve is cut or not. Thus, in their practice, the authors do not cut the nerve to save surgical time. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. PMID- 22094765 TI - Discussion: the significance of latissimus dorsi flap innervation in delayed breast reconstruction: a prospective randomized study-magnetic resonance imaging and histologic findings. PMID- 22094766 TI - Mast cells are required in the proliferation and remodeling phases of microdeformational wound therapy. AB - BACKGROUND: Mast cells are important in numerous inflammatory processes. They are also mechanosensitive and likely play an important role in wound healing. The authors hypothesized that mechanical alteration of the wound environment with a distributed suction device could link mast cells to the healing cascade. METHODS: Controlled uniform full-thickness wound surface microdeformations were induced by suction combined with an open-pore polyurethane foam (microdeformational wound therapy) in mast cell-deficient WWv mice and their mast cell-sufficient littermates. Wound healing parameters were assessed in the inflammatory, proliferative, and remodeling phases of healing. RESULTS: Wound tissue granulation, cell proliferation, blood vessel sprouting, and collagen maturation were found to be mast cell-dependent throughout the proliferating and remodeling stages of healing. CONCLUSION: Mast cells are critical in the robust granulation tissue response seen in microdeformational wound therapy and in the modulation of the remodeling phase of wound healing. PMID- 22094767 TI - Discussion: mast cells are required in the proliferation and remodeling phases of microdeformational wound therapy. PMID- 22094768 TI - Modulation of immune response and T-cell regulation by donor adipose-derived stem cells in a rodent hind-limb allotransplant model. AB - BACKGROUND: In this study, the authors investigated whether donor adipose-derived stem cells have immunomodulatory effects, such as regulation of T cells, modulation of related cytokines, and prolongation of composite tissue allotransplantation survival, in a rodent hind-limb model. METHODS: Adipose derived stem cells were obtained from donor adipose tissue and co-cultured with CD3 T cells from allogenic splenocytes for in vitro studies. Orthotopic hind-limb allotransplants were performed from Brown Norway to Lewis rats (day 0). Group 1 (control group) did not receive any treatment. Group 2 received cyclosporin A on days 0 to 20. Group 3 received antilymphocyte serum (day -4 and day 1) and cyclosporin A (days 0 to 20). Group 4 received cyclosporin A (days 0 to 20), antilymphocyte serum (day -4 and day 1), and adipose-derived stem cells (2 * 10 cells/time administered intravenously on days 7, 14, and 21). RESULTS: Adipose derived stem cells exert immunomodulatory effects including suppressing T-cell proliferation and increasing CD4/CD25/Foxp3 regulatory T cells in vitro. The in vivo study revealed that, compared with untreated control, rats administered adipose-derived stem cells along with transient antilymphocyte serum and cyclosporin A treatment had significantly prolonged allotransplant survival (p < 0.001), decreased allotissue rejection, significantly elevated donor cell chimerism, and increased CD4/CD25/Foxp3 regulatory T cells in peripheral blood and alloskin tissue with up-regulation of transforming growth factor-beta and interleukin-10 levels. CONCLUSIONS: In combination with transient immunosuppression, adipose-derived stem cells modulate the immune system and significantly prolong allotransplant survival. The underlying mechanisms include changes in antiinflammatory cytokine expression and T-cell functions. PMID- 22094769 TI - Lack of FGF-7 further delays cutaneous wound healing in diabetic mice. AB - BACKGROUND: The authors have previously demonstrated that normal mice lacking fibroblast growth factor (FGF)-7 can heal cutaneous wounds normally, likely as a result of various compensatory mechanisms. In this study, the authors explored the role of FGF-7 on wound healing in diabetic mice. METHODS: Full-thickness excisional dorsal wounds were created in FGF-7-null diabetic (FGF-7 Lepr, experimental group, n = 8), FGF-7-null (FGF-7 Lepr, FGF-7-null group, n = 8), diabetic (FGF-7 Lepr, diabetic group, n = 11), and wild-type (FGF-7 Lepr, wild type group, n = 11) mice. Wound closure was followed by digital planimetry. Wound tissues were harvested on day 7 for immunohistochemical staining of cell proliferation (Ki67) and real-time polymerase chain reaction. RESULTS: As expected, the experimental and diabetic groups had significantly slower wound healing than the FGF-7-null or wild-type group. The absence of FGF-7, however, further delayed wound healing in diabetic mice. Curiously, the contraction rate in the experimental group was significantly lower than that in the diabetic group, whereas the epithelialization rate in experimental mice was comparable to that in the diabetic group. Real-time polymerase chain reaction expression of growth factors, including transforming growth factor-beta1, basic fibroblast growth factor, and epidermal growth factor in experimental mice, was also generally lower than that in diabetic mice. CONCLUSIONS: Although the lack of FGF 7 did not appear to affect reepithelialization of cutaneous wounds even in diabetic mice, it significantly reduced the wound contraction rate of healing by further altering the dermal components in diabetic mice. Given the specifically targeted effects of FGF-7 on epithelial cells, the authors' findings suggest that further FGF-7-dependent epithelial-mesenchymal interaction exists that may be important in diabetic wound healing. PMID- 22094770 TI - Update on ischemia-reperfusion injury for the plastic surgeon: 2011. AB - Ischemia-reperfusion injury occurs when tissue is reperfused following a prolonged period of ischemia. It is a subject of interest to plastic surgeons involved in replantation, free tissue transfer, and composite tissue allotransplantation, as it can have a significant impact on the overall success of these procedures. The purpose of this article is to review the recent progress in the investigation of ischemia-reperfusion injury in skeletal muscle and skin and to highlight the potential clinical implications of therapeutic interventions aimed at reducing ischemia-reperfusion injury. PMID- 22094771 TI - Discussion: treatment of facial paralysis: dynamic reanimation of spontaneous facial expression-apropos of 655 patients. PMID- 22094772 TI - An update on facial transplantation cases performed between 2005 and 2010. AB - BACKGROUND: Since 2005, 13 facial allotransplantation cases have been performed worldwide. The major indications for these facial allotransplantations were neurofibromatosis and trauma injuries, including animal bites, burns, falls, and shotgun blasts. METHODS: An analysis of 13 facial transplantation cases was performed by reviewing the anatomical details, microsurgical techniques, and functional outcomes according to the follow-up information based on the literature, meeting presentations, and media reports. RESULTS: The male-to-female ratio was 11:2. Two male patients died at 2 months and 2 years, respectively, after transplantation because of transplant- and infection-related problems. Eleven face transplant recipients are alive. The composite tissue allotransplants included cutaneous, myocutaneous, and osteomyocutaneous components. Most of these facial allotransplants were partial, one was nearly total, and two were announced as total face transplantations. CONCLUSIONS: This report provides a useful overview of the technical aspects of face transplantation; however, the reports on long-term functional and aesthetic outcomes will help to define the future of face transplantation. PMID- 22094773 TI - Use of desmopressin for unremitting epistaxis following septorhinoplasty and turbinectomy. AB - BACKGROUND: Cauterization, nasal packing, and topical and/or injection of intranasal vasoconstrictors have been the mainstay of treatment for epistaxis following outpatient nasal surgery. In this study, the authors report the clinical outcomes in a cohort of patients with postoperative epistaxis managed with a single dose of intravenous desmopressin. METHODS: A retrospective chart review of 268 consecutive nasal operations (rhinoplasty, septoplasty, and/or turbinectomy for cosmetic and/or functional purposes) was conducted. Information on demographics, perioperative blood pressure, postoperative management, and effectiveness of the measures used was assessed. The primary outcome variable was cessation of bleeding. RESULTS: Nine patients were identified who experienced excessive postoperative bleeding following discharge from the surgical facility. Each patient received 0.3 MUg/kg of intravenous desmopressin over 30 minutes under the supervision of the local emergency room physician with verbal instructions from the treating plastic surgeon. After administration of desmopressin, bleeding either stopped completely (eight patients) or slowed down significantly to allow discharge (one patient). No significant adverse side effects of desmopressin were observed. No patient was known to be taking medication negatively affecting coagulation perioperatively. Preoperatively, two patients were documented to have von Willebrand disease and thus received desmopressin preoperatively. Average blood pressure was 116/71 mmHg intraoperatively (range, 109 to 126/66 to 83 mmHg) and 118/74 mmHg postoperatively (range, 105 to 129/65 to 85 mmHg). CONCLUSION: Unremitting postoperative epistaxis following outpatient nasal surgery can be successfully controlled by a protocol using intravenous desmopressin without the need for alternative maneuvers. PMID- 22094774 TI - Abdominal musculoaponeuretic system: magnetic resonance imaging evaluation before and after vertical plication of rectus muscle diastasis in conjunction with lipoabdominoplasty. AB - BACKGROUND: The purposes of this study were to compare preoperative magnetic resonance imaging and intraoperative measurements of rectus diastasis and to evaluate the long-term durability of the plication of the anterior rectus fascia. METHODS: Twenty consecutive cases of middle-aged female subjects undergoing lipoabdominoplasty and rectus plication were studied by magnetic resonance imaging preoperatively and between 6 months and 25 months postoperatively. Images were obtained in the T1 axial, T2 axial, sagittal, and coronal planes. Rectus diastasis was measured at the maximum. Rectus muscle thickness and width were measured, and abdominal circumferences were measured in the anteroposterior and transverse planes at the midpoint from the xiphisternum to the umbilicus and the midpoint from the umbilicus to the symphysis pubis corresponding approximately to the lumbar-2 and sacral-3 vertebral bodies. RESULTS: The absence of diastasis can be precisely measured by magnetic resonance imaging. Postoperative diastasis was not seen in any of the cases followed up to 25 months. The preoperative magnetic resonance imaging diastasis values were consistently less than the intraoperatve measurements; however, this was attributed to muscle relaxation at surgery due to muscle relaxants during general anesthesia. There was a significant reduction in waistlines in both the anteroposterior and transverse dimensions measured by magnetic resonance imaging. CONCLUSIONS: Surgical repair of rectus muscle diastasis is a durable procedure, and magnetic resonance imaging follow-up is an excellent way to see the durability of the procedure. Magnetic resonance imaging is not operator-dependent and has no interobserver variations. It has the advantage of being a safe, radiation-free procedure with repeatability and dependability. PMID- 22094775 TI - Establishing a multidisciplinary academic cosmetic center. AB - The demand for cosmetic services has risen rapidly in recent years, but has slowed down with the current economic downturn. Managed care organizations and Medicare have been steadily reducing their reimbursements for physician services. The payment for reconstructive surgical procedures has been decreasing and is likely to worsen with healthcare reform, and many plastic surgery residency programs are facing fiscal challenges. An adequate volume of patients needing cosmetic services is necessary to recruit and train the best candidates to the residency programs. Self-pay patients will help ensure the fiscal viability of plastic surgery residency programs. Attracting patients to an academic healthcare center will become more difficult in a recession without the appropriate facilities, programs, and pricing strategies. Setting up a modern cosmetic services program at an academic center has some unique challenges, including funding, academic politics, and turf. The authors opened a free-standing academic multidisciplinary center at their medical school 3 years ago. The center is an off-site, 13,000-sq ft facility that includes faculty from plastic surgery, ear, nose, and throat, dermatology, and vascular surgery. In this article, the authors discuss the process of developing and executing a plan for starting an aesthetic services center in an academic setting. The financing of the center and factors in pricing services are discussed. The authors show the impact of the center on their cosmetic surgery patient volumes, resident education, and finances. They expect that their experience will be helpful to other plastic surgery programs at academic medical centers. PMID- 22094776 TI - Face lift. AB - LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Identify and describe the anatomy of and changes to the aging face, including changes in bone mass and structure and changes to the skin, tissue, and muscles. 2. Assess each individual's unique anatomy before embarking on face-lift surgery and incorporate various surgical techniques, including fat grafting and other corrective procedures in addition to shifting existing fat to a higher position on the face, into discussions with patients. 3. Identify risk factors and potential complications in prospective patients. 4. Describe the benefits and risks of various techniques. SUMMARY: The ability to surgically rejuvenate the aging face has progressed in parallel with plastic surgeons' understanding of facial anatomy. In turn, a more clear explanation now exists for the visible changes seen in the aging face. This article and its associated video content review the current understanding of facial anatomy as it relates to facial aging. The standard face-lift techniques are explained and their various features, both good and bad, are reviewed. The objective is for surgeons to make a better aesthetic diagnosis before embarking on face-lift surgery, and to have the ability to use the appropriate technique depending on the clinical situation. PMID- 22094777 TI - Wendell L. Hughes' life and contributions to plastic surgery. AB - Wendell L. Hughes was a pioneer in ophthalmic plastic surgery and best known for the "Hughes flap," a tarsoconjunctival flap used for lower eyelid reconstruction. In 1937, Wendell L. Hughes sought to achieve the criterion standard of replacing "like with like" in his development of the tarsoconjunctival flap for lower lid reconstruction. This work was published in his ground-breaking thesis, Reconstructive Surgery of the Eyelids, the most comprehensive book on ophthalmic plastic surgery of its time. Although this flap has undergone many modifications, it has stood the test of time and is still used today. In addition, Dr. Hughes was heavily involved in surgical education, a founding member of the American Board of Plastic Surgery, and a leader in the development of sutures and microneedles. More importantly, he was a gracious humanitarian and inspiring mentor loved by peers and patients alike. Other authors have reviewed the intricacies of the Hughes flap; however, little attention has been given to the contributions of its creator. PMID- 22094778 TI - Septal cartilage graft for posttraumatic ear reconstruction. PMID- 22094780 TI - What about the informed consent for breast implantation? PMID- 22094781 TI - Alternative method for volume improvement in autologous breast reconstruction. PMID- 22094783 TI - Clinical analyses of clustered microcalcifications after autologous fat injection for breast augmentation. PMID- 22094785 TI - Discussion: macrolane for breast enhancement: 12-month follow-up. PMID- 22094786 TI - Malrotation of the McGhan style 510 prosthesis. PMID- 22094788 TI - Complications in postbariatric body contouring based on different weight loss methods. PMID- 22094790 TI - Alternative materials in vacuum-assisted closure. PMID- 22094792 TI - Major pedicles of the sartorius muscle. PMID- 22094794 TI - The skin irritation of common suture materials. PMID- 22094795 TI - Plastic surgeons' satisfaction with work-life balance: results from a national survey. PMID- 22094797 TI - Ribosome display: a perspective. AB - Ribosome display is an in vitro evolution technology for proteins. It is based on in vitro translation, but prevents the newly synthesized protein and the mRNA encoding it from leaving the ribosome. It thereby couples phenotype and genotype. Since no cells need to be transformed, very large libraries can be used directly in selections, and the in vitro amplification provides a very convenient integration of random mutagenesis that can be incorporated into the procedure. This review highlights concepts, mechanisms, and different variations of ribosome display and compares it to related methods. Applications of ribosome display are summarized, e.g., the directed evolution of proteins for higher binding affinity, for higher stability or other improved biophysical parameters and enzymatic properties. Ribosome display has developed into a robust technology used in academia and industry alike, and it has made the cell-free Darwinian evolution of proteins over multiple generations a reality. PMID- 22094796 TI - Survivorship of second-generation metal-on-metal primary total hip replacement. AB - BACKGROUND: Second generation metal-on-metal total hip replacements (THR) were introduced in the late 1980s and various studies reported conflicting data on their outcome. METHODS: Implant survival of 1,270 second-generation 28 mm metal on-metal primary THR in 1,121 patients followed prospectively at a mean of 6.8 years postoperatively was evaluated retrospectively. The probability of survival at 10 years was estimated using the method of Kaplan and Meier, and relative risk factors including age, gender, BMI, type of implant fixation and component size were calculated using the Cox proportional-hazards model. RESULTS: Sixty-three (5%) THRs were revised, these being 28 hips for aseptic loosening and 35 for reasons other than aseptic loosening. The probability of survival at 10 years, with revision for any reason as the endpoint, was 0.90 (95% confidence interval (CI) 0.86-0.94) for the THR as a whole, 0.91 (95% CI 0.87-0.95) for the cup, and 0.96 (95% CI 0.94-0.98) for the stem. No demographic factors or covariates were found to significantly affect the implant survivorship. DISCUSSION: As there was no superior probability of survival, and there have been concerns on putative local and systemic toxicity of metal debris, the use of second-generation metal on-metal articulations for primary THR remains moot. PMID- 22094798 TI - Preparation and testing of E. coli S30 in vitro transcription translation extracts. AB - Crude cell-free extracts are useful tools for investigating biochemical phenomena and exploiting complex enzymatic processes such as protein synthesis. Extracts derived from E. coli have been used for over 50 years to study the mechanism of protein synthesis. In addition, these S30 extracts are commonly used as a laboratory tool for protein production. The preparation of S30 extract has been streamlined over the years and now it is a relatively simple process. The procedure described here includes some suggestions for extracts to be used for ribosome display. PMID- 22094799 TI - Eukaryotic ribosome display selection using rabbit reticulocyte lysate. AB - Ribosome display is a powerful in vitro technology for the selection and directed evolution of proteins. Cell-free translation is central to the ribosome display process and is performed in such a way that the ribosome provides the link between genotype and phenotype that allows genes encoding proteins with desired properties to be identified by selection. Prokaryotic cell-free translation reagents, based initially on E. coli cell extracts and more recently containing purified and recombinant factors, have dominated the ribosome display literature. Eukaryotic cell extracts are also suitable for ribosome display; however, protocols for prokaryotic ribosome display are not directly transferable to the use of eukaryotic cell extracts. This chapter describes an optimised methodology for the use of rabbit reticulocyte lysate for ribosome display selections. PMID- 22094800 TI - Stabilized ribosome display for in vitro selection. AB - Ribosome display is a very effective and powerful technology for screening functional peptides or polypeptides in vitro. In ribosome display, each peptide or polypeptide (phenotype) links with its corresponding mRNA (genotype) through a ribosome. This link can be achieved by the absence of a stop codon in the mRNA, therefore stalling the ribosome at the end of translation with the nascent random sequence peptide extended by a spacer outside of the ribosome tunnel. In this chapter, we describe a method for the use of a further stabilized peptide ribosome-mRNA complex for ribosome display. PMID- 22094801 TI - Eukaryotic ribosome display with in situ DNA recovery. AB - Ribosome display is a cell-free display technology for in vitro selection and optimisation of proteins from large diversified libraries. It operates through the formation of stable protein-ribosome-mRNA (PRM) complexes and selection of ligand-binding proteins, followed by DNA recovery from the selected genetic information. Both prokaryotic and eukaryotic ribosome display systems have been developed. In this chapter, we describe the eukaryotic rabbit reticulocyte method in which a distinct in situ single-primer RT-PCR procedure is used to recover DNA from the selected PRM complexes without the need for prior disruption of the ribosome. PMID- 22094802 TI - mRNA display using covalent coupling of mRNA to translated proteins. AB - mRNA display is a powerful technique that allows for covalent coupling of a translated protein with its coding mRNA. The resulting conjugation between genotype and phenotype can be used for the efficient selection and identification of peptides or proteins with desired properties from an mRNA-displayed peptide or protein library with high diversity. This protocol outlines the principle of mRNA display and the detailed procedures for the synthesis of mRNA-protein fusions. Some special considerations for library construction, generation, and purification are discussed. PMID- 22094803 TI - SNAP display: in vitro protein evolution in microdroplets. AB - SNAP display is based on the covalent reaction of the DNA repair protein AGT (O(6)-alkylguanine DNA alkyltransferase, the "SNAP-tag") with its substrate benzylguanine (BG). Linear, BG-labelled template DNA is encapsulated in water-in oil emulsion droplets with a diameter of a few micrometres (i.e. 1 mL of emulsion contains ~10(10) compartments). Each droplet contains only a single DNA copy, which is transcribed and translated in vitro. The expressed AGT fusion proteins attach to their coding DNA via the BG label inside the droplet, which ensures that a specific genotype-phenotype linkage is established. Subsequently, the emulsion is broken and protein-DNA conjugates, which constitute a DNA-tagged protein library, selected via affinity panning. This method will prove a useful addition to the array of in vitro display systems, distinguished by the stability of DNA as the coding nucleic acid and the covalent link between gene and protein. PMID- 22094805 TI - Optimisation of antibody affinity by ribosome display using error-prone or site directed mutagenesis. AB - Affinity optimisation of antibodies can be achieved with great success by using directed evolution approaches, that is, the creation of and selection from diverse libraries. Here, we describe in detail methods to optimise antibody affinity for an antigen through directed evolution using ribosome display. Diversification of antibody single chain variable (scFv) domains is carried out by error-prone PCR and oligonucleotide-directed mutagenesis to generate random and targeted libraries respectively. Subsequent libraries are converted to ribosome display format and taken through cycles of transcription, translation, and selection. Since the starting point and the recovered product are linear DNA, this can easily be manipulated further to allow accumulation of beneficial mutations through iterative cycles of selection. PMID- 22094804 TI - cDNA display: rapid stabilization of mRNA display. AB - The cDNA display method is a robust in vitro display technology that converts an unstable mRNA-protein fusion (mRNA display) to a stable mRNA/cDNA-protein fusion (cDNA display) whose cDNA is covalently linked to its encoded protein using a well-designed puromycin linker. We provide technical details for preparing cDNA display molecules and for the synthesis of the puromycin linker for the purpose of screening the functional proteins and peptides. PMID- 22094806 TI - Affinity maturation of phage display antibody populations using ribosome display. AB - Ribsosome display is a PCR-based in vitro display technology that it well suited for the selection and evolution of high-affinity antibodies. In particular, ribosome display lends itself to the evolution of functional characteristics, such as potency, and thereby facilitates the production of therapeutic antibodies from lead candidates. In this chapter, we describe how to mature large phage display antibody populations (>10(7)) by performing increasingly stringent selections with decreasing antigen concentration. This process takes advantage of ribosome display's intrinsic ability to evolve sequence during selection. Ribosome display can also be used as a complementary tool to phage display for isolating high-affinity antibodies from naive libraries. Ultimately, maturation of large antibody populations by ribosome display will help to speed up the process of generating antibody therapeutics. PMID- 22094807 TI - Evolution of protein stability using ribosome display. AB - The opportunity to enhance protein stability has a number of potential benefits for biological therapeutics - for example extending in vivo half-life, enabling a longer shelf life, reducing the propensity to aggregate, or enabling soluble expression. Engineering protein stability has been attempted empirically, rationally, and using directed evolution based on phage display. Ribosome display is a powerful in vitro technology for the selection and directed evolution of proteins. Ribosome display is typically used for the generation of high-affinity proteins and peptides. This method extends the utility of ribosome display to selecting for stability, defined as the propensity of a molecule to exist in its folded and active state. PMID- 22094808 TI - Selection of lead antibodies from naive ribosome display antibody libraries. AB - A large antibody fragment library (>10(12)) has been generated in ribosome display format. The library was constructed in a two-step process. First, variable (V) genes were isolated from human B cells from a panel of 14 donors and cloned into designated ribosome display vectors to create a gene bank. Second, RD VH and RD-VL genes from individual immunoglobulin families were combined in vitro resulting in 112 scFv ribosome display sub-libraries. These were subsequently pooled to form a master library.This library was used to isolate a panel of antibodies to the IL4 receptor by three rounds of selections on a soluble target. PMID- 22094809 TI - Evolution of disulfide-rich peptide aptamers using cDNA display. AB - Protein scaffolds containing some disulfide bonds (e.g., Knottin, Kunitz domain, etc.) are promising candidates for molecular recognition. cDNA display has been developed to screen functional disulfide-rich peptide aptamers from a vast library by promoting disulfide bond shuffling after the synthesis of peptides in a cell-free translation system. Here we present a detailed protocol for the selection of disulfide-rich peptide aptamers against interleukin 6 receptor (IL 6R) from a 35-amino acid peptide library containing 32 amino acids in the random region, which is linked to its genotype by cDNA display. PMID- 22094810 TI - Peptide screening using PURE ribosome display. AB - To demonstrate directed protein evolution or selection of functional polypeptides, ribosome display is one of the most ideal technologies of evolutionary engineering. Intrinsic components, such as nucleases in the cell extract-based cell-free protein synthesis systems, reduce the stability of the messenger RNA-ribosome-polypeptide ternary complex, thereby preventing the attainment of reliable results. To overcome this problem, we have developed an effective and highly controllable ribosome display system using the protein synthesizing using recombinant elements (PURE) system. Since the activities of nucleases and other inhibitory factors are very low in the PURE system, the ternary complex is highly stable and the selected mRNA can be reliably recovered. Using this system, we were able to select peptides that specifically bind to monoclonal antibodies from random peptide libraries. The advantages of the modified PURE system for ribosome display strongly substantiate its usability. PMID- 22094811 TI - Rapid selection of high-affinity binders using ribosome display. AB - Ribosome display has proven to be a powerful in vitro selection and evolution method for generating high-affinity binders from libraries of folded proteins. It has been successfully applied to single-chain Fv fragments of antibodies and alternative scaffolds, such as Designed Ankyrin Repeat Proteins (DARPins). High affinity binders with new target specificity can be obtained from highly diverse DARPin libraries in only a few selection rounds. In this protocol, the selection from the library and the process of affinity maturation and off-rate selection are explained in detail. PMID- 22094812 TI - mRNA display-based selections using synthetic peptide and natural protein libraries. AB - mRNA display is a powerful in vitro selection technique that can be applied toward the identification of peptides or proteins with desired properties. The physical conjugation between a protein and its own RNA presents unique challenges in manipulating the displayed proteins in an RNase-free environment. This protocol outlines the generation of synthetic peptide and natural proteome libraries as well as the steps required for generation of mRNA-protein fusion libraries, in vitro selection, and regeneration of the selected sequences. The selection procedures for the identification of Ca(2+)-dependent, calmodulin binding proteins from synthetic peptide and natural proteome libraries are presented. PMID- 22094813 TI - Identification of candidate vaccine genes using ribosome display. AB - In vitro protein selection methods that are not biased by the context of living organisms allow the screening of genomic expression libraries against a large number of different ligands. As such, ribosome display is a powerful technology for the in vitro selection of proteins or peptides from large PCR-derived libraries. Libraries can be generated from the genomic fragments of pathogens, thus allowing potential vaccine genes and the immunologically relevant proteins of pathogens to be identified and mapped using ribosome display. This chapter describes a methodology for the use of ribosome display for the identification of potential vaccine genes for the bacterial pathogen APP-5. PMID- 22094814 TI - Ribosome display for the selection of Sac7d scaffolds. AB - Combinatorial libraries of Sac7d have proved to be a valuable source of proteins with favorable biophysical properties and novel ligand specificities, so-called Nanofitins. Thus, Sac7d represents a promising scaffold alternative to antibodies for biotechnological and potentially clinical applications. We describe here the methodology for the construction of a library of Sac7d and its use for selection by ribosome display. PMID- 22094815 TI - Charging of tRNAs using ribozymes and selection of cyclic peptides containing thioethers. AB - In vitro selection methods represent a powerful approach toward identifying high affinity peptide ligands from highly diverse peptide libraries against a desired target. We herein describe a method for the display and selection of cyclic thioether peptide libraries. Reprogramming the initiation event from fMet to an N chloroacetyl-amino acid by utilizing flexizyme to rapidly and efficiently prepare the aa-tRNA can be effectively used to initiate translation, upon which the thiol group of an inserted cysteine at the C terminus of the designed library spontaneously reacts to yield a nonreducible cyclic thioether peptide readily compatible with any in vitro display methods. Thus, cyclic peptides already in a nonreducible stable form can be selected directly against the target of interest. PMID- 22094816 TI - Update on pure translation display with unnatural amino acid incorporation. AB - The identification of peptide and protein ligands by directed evolution in vitro has been of enormous utility in molecular biology and biotechnology. However, the translation step in almost all polypeptide selection methods is performed in vivo or in crude extracts, restricting applications. These restrictions include a limited library size due to transformation efficiency, unwanted competing reactions in translation, and an inability to incorporate multiple unnatural amino acids (AAs) with high fidelity and efficiency. These restrictions can be addressed by "pure translation display" where the translation step is performed in a purified system. To date, all pure translation display selections have coupled genotype to phenotype in a ribosome display format, though other formats also should be practical. Here, we detail the original, proof-of-principle, pure translation-display method because this version should be the most suitable for encoding multiple unnatural AAs per peptide product toward the goal of "peptidomimetic evolution." Challenges and progress toward this ultimate goal are discussed and are mainly associated with improving the efficiency of ribosomal polymerization of multiple unnatural AAs. PMID- 22094817 TI - In vitro selection of unnatural cyclic peptide libraries via mRNA display. AB - The ribosomal synthesis of drug-like peptides containing unnatural amino acids is possible due to the broad substrate specificity of the ribosome. In this protocol, a reconstituted Escherichia coli ribosomal translation system (PURE) is adapted to incorporate unnatural amino acids into mRNA-displayed peptide libraries, which are used in in vitro selection. PMID- 22094818 TI - Optimization of CAT-354, a therapeutic antibody directed against interleukin-13, using ribosome display. AB - In this case study, we describe the use of in vitro protein evolution with ribosome display to improve the potency of a human interleukin-13-neutralising antibody by a factor of over 200-fold and derive a therapeutic candidate, CAT 354, for the treatment of asthma. A combination of directed and random mutagenesis enabled the identification of highly potent neutralising antibodies and highlighted the advantage of the ribosome display protein evolution approach in identifying beneficial mutations across the entire sequence space. This chapter describes in detail the process followed to achieve a successful in vitro affinity maturation outcome using ribosome display technology. PMID- 22094819 TI - Affinity maturation and functional dissection of a humanised anti-RAGE monoclonal antibody by ribosome display. AB - The pursuit of more potent, safe, and cost-effective drugs has placed a greater emphasis on antibody optimisation within the drug discovery process. Technologies to rapidly improve antibody drug performance, such as phage display, ribosome display, and yeast display, are playing a key role in this effort. Among these ribosome display is a particularly powerful technology and has recently been applied to the affinity optimisation of a humanised anti-receptor for advanced glycation end products (anti-RAGE) antibody (Finlay et al., J Mol Biol 388:541 558, 2009). By using a combination of error-prone PCR with ribosome display each amino acid position within this humanised antibody was scanned for both its functional importance and its capacity to increase affinity resulting in both affinity-matured antibody variants and a functional map of the antibody paratope. PMID- 22094820 TI - Crystallographic relationships in the crossed lamellar microstructure of the shell of the gastropod Conus marmoreus. AB - The crossed lamellar microstructure of mollusk shells shows a very complex hierarchical architecture constituted of long rod-shaped aragonite crystals stacked parallel to each other inside each first order lamella, which are almost perpendicular to the ones contained in parallel neighboring lamellae. To better understand the construction and properties of the crossed lamellar microstructure we have performed a detailed study to determine the crystallographic characteristics and their evolution during shell growth using scanning electron microscopy, transmission electron microscopy and X-ray diffraction texture analysis. The arrangement of crystals is rationalized by a set of twin law relationships between aragonite crystals. Specifically, the aragonite rods, or third order lamellae within each first order lamella, internally consist of polysynthetic twins bounded by {110} mirror planes. In turn, the polysynthetically twinned aragonite crystals also show a constant crystallographic orientation with respect to aragonite crystals in adjacent first order lamellae. It can be seen as another twin law in which crystals from adjacent lamellae are bounded by (110) planes but with their c-axes rotated within this plane by 30 degrees . Thus there are two sets of twin laws that relate crystal units at lower (third order lamellae) and higher (first order lamellae) length scales. These hierarchical relationships play a crucial role in the construction, organization and properties of this complex microstructure. The later orientational relationships have never been described in geological aragonite and are only found in biogenic materials with a crossed lamellar microstructure. Their occurrence is probably determined by the presence of shell organic components which regulate crystal growth and may favor unusual crystallographic relationships. PMID- 22094822 TI - A digital microfluidic platform for primary cell culture and analysis. AB - Digital microfluidics (DMF) is a technology that facilitates electrostatic manipulation of discrete nano- and micro-litre droplets across an array of electrodes, which provides the advantages of single sample addressability, automation, and parallelization. There has been considerable interest in recent years in using DMF for cell culture and analysis, but previous studies have used immortalized cell lines. We report here the first digital microfluidic method for primary cell culture and analysis. A new mode of "upside-down" cell culture was implemented by patterning the top plate of a device using a fluorocarbon liftoff technique. This method was useful for culturing three different primary cell types for up to one week, as well as implementing a fixation, permeabilization, and staining procedure for F-actin and nuclei. A multistep assay for monocyte adhesion to endothelial cells (ECs) was performed to evaluate functionality in DMF-cultured primary cells and to demonstrate co-culture using a DMF platform. Monocytes were observed to adhere in significantly greater numbers to ECs exposed to tumor necrosis factor (TNF)-alpha than those that were not, confirming that ECs cultured in this format maintain in vivo-like properties. The ability to manipulate, maintain, and assay primary cells demonstrates a useful application for DMF in studies involving precious samples of cells from small animals or human patients. PMID- 22094823 TI - Selectively bonded polymeric glaucoma drainage device for reliable regulation of intraocular pressure. AB - A novel glaucoma drainage device (GDD) using a polymeric micro check valve with no reverse flow is presented for the effective regulation of intraocular pressure (IOP). A significant functional improvement was achieved by reducing the possible incidence of hypotony, as the proposed GDD only drains aqueous humor at a certain cracking pressure or higher. The device consists of three biocompatible polymer layers: a top layer (cover), an intermediate layer (membrane), and a bottom layer (base plate with a cannula). All three layers, made of soft polydimethylsiloxane (PDMS), were bonded together to realize the thin GDDs. The bottom layer was selectively coated with chromium (Cr)/gold (Au) to prevent stiction between the valve seat and the valve orifice so that the device could show enhanced reliability in operation and high yield in production. Two types of polymeric devices were fabricated; one was a glaucoma drainage device for humans (GDDH) and the other was a glaucoma drainage device for animals (GDDA). From subsequent in vitro tests, the cracking pressures were 18.33 +/- 0.66 mmHg (mean +/- standard deviation) for GDDH and 12.42 mmHg for GDDA, both of which were very close to the corresponding normal IOPs. From in vivo tests of GDDA, the IOP of all implanted devices was properly regulated within the target pressure (10-15 mmHg). The experimental results showed that the proposed polymeric GDD has high potential for use in the treatment of glaucoma disease in terms of its repeatability of the cracking pressure and patients' relief from post-operative discomfort. PMID- 22094821 TI - Combinatorial insulin secretion dynamics of recombinant hepatic and enteroendocrine cells. AB - One of the most promising cell-based therapies for combating insulin-dependent diabetes entails the use of genetically engineered non-beta cells that secrete insulin in response to physiologic stimuli. A normal pancreatic beta cell secretes insulin in a biphasic manner in response to glucose. The first phase is characterized by a transient stimulation of insulin to rapidly lower the blood glucose levels, which is followed by a second phase of insulin secretion to sustain the lowered blood glucose levels over a longer period of time. Previous studies have demonstrated hepatic and enteroendocrine cells to be appropriate hosts for recombinant insulin expression. Due to different insulin secretion kinetics from these cells, we hypothesized that a combination of the two cell types would mimic the biphasic insulin secretion of normal beta cells with higher fidelity than either cell type alone. In this study, insulin secretion experiments were conducted with two hepatic cell lines (HepG2 and H4IIE) transduced with 1 of 3 adenoviruses expressing the insulin transgene and with a stably transfected recombinant intestinal cell line (GLUTag-INS). Insulin secretion was stimulated by exposing the cells to glucose only (hepatic cells), meat hydrolysate only (GLUTag-INS), or to a cocktail of the two secretagogues. It was found experimentally that the recombinant hepatic cells secreted insulin in a more sustained manner, whereas the recombinant intestinal cell line exhibited rapid insulin secretion kinetics upon stimulation. The insulin secretion profiles were computationally combined at different cell ratios to arrive at the combinatorial kinetics. Results indicate that combinations of these two cell types allow for tuning the first and second phase of insulin secretion better than either cell type alone. This work provides the basic framework in understanding the secretion kinetics of the combined system and advances it towards preclinical studies. PMID- 22094824 TI - Integration of nanoparticle cell lysis and microchip PCR for one-step rapid detection of bacteria. AB - This paper describes an integrated microchip system as an efficient and cost effective solution involving Nanotechnology and Lab-on-a-Chip technology for the rapid detection of bacteria. The system is based on using surface-modified gold nanoparticles for efficient cell lysis followed by microchip PCR without having to remove the nanoparticles from the PCR solution. Poly(quaternary ammonium) modified gold nanoparticles are used to provide a novel and efficient cell lysis method without the need to go through time-consuming, expensive and complicated microfabrication processes as most of current cell lysis methods for Lab-on-a Chip applications do. It also facilitates the integration of cell lysis and PCR by sharing the same reaction chamber as PCR uses. It is integrated with a prototype microchip PCR system consisting of a physical microchip PCR device and an automated temperature control mechanism. The research work explores solutions for the problem of PCR inhibition caused by gold nanoparticles as well as for the problem of non-specific PCR amplification in the integrated microchip system. It also explores the possibility of greatly reducing PCR cycling time to achieve the same result compared to the protocol for a regular PCR machine. The simplicity of the setup makes it easy to be integrated with other Lab-on-a-Chip functional modules to create customized solutions for target applications. PMID- 22094825 TI - Improvements in speech perception after the upgrade from the TEMPO+ to the OPUS 2 audio processor. AB - OBJECTIVE: To assess if speech perception improves after the upgrade from the TEMPO+ to the OPUS 2 processor. METHOD: In this retrospective study, 45 subjects (54 ears) implanted with a cochlear implant were upgraded from the TEMPO+ (continuous interleaved sampling + coding strategy) to the OPUS 2 processor (fine structure processing). Before the upgrade, patients were tested with the Freiburg monosyllable (FM) and the Hochmair-Schulz-Moser (HSM) sentence test in quiet and in noise. Four weeks after the upgrade, subjects were again assessed with the same tests. RESULTS: In quiet, mean FM results improved from 62.0% (+/-21.3%) to 77.8% (+/-15.2%) and HSM sentences from 69.9% (+/-26.1%) to 77.9% (+/-22.1%). In noise, mean FM results improved from 27.3% (+/-17.1%) to 52.1% (+/-18.6%) and HSM sentences from 40.4% (+/-29.1%) to 58.0% (+/-26.1%). The upgrade to the OPUS 2 was statistically very significant for all speech perception tests (p < 0.001). Additionally, subjects stated that the OPUS 2 initially sounded 'awkward' but that quality and speech perception improved after a certain adaptation time. CONCLUSION: Speech understanding in quiet and noise significantly improved with the OPUS 2 in all speech perception tests. PMID- 22094827 TI - Differential diagnosis in a primary care population with presumed airway obstruction: a real-life study. AB - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) have major symptoms in common. However, the mode of the underlying chronic airway inflammation is different. There is still no single diagnostic test that can be considered a gold standard to distinguish asthma from COPD. OBJECTIVES: To determine the diagnostic accuracy for asthma and COPD of a series of diagnostic steps in a population older than 40 years with probable obstructive airway disease (OAD) in primary care. METHODS: In this prospective cohort study, patients without a certain diagnosis underwent a work-up, including office spirometry by their general practitioner (GP). They were then referred to a pulmonologist, and they had control visits with their GP. The diagnostic gain of subsequent steps was calculated for 2 endpoints, namely the specialist's opinion and the GP's final opinion. RESULTS: Up to 60% of the patients failed to consult with the pulmonologist. For this subgroup, the office spirometry induced significantly more diagnostic congruency than any other diagnostic step. The specialists rejected 44.5% of the diagnoses made by the GPs, including spirometry. High values of diagnostic gain were found after the office spirometry and after the specialist's advice. Up to 25% of the population taking bronchodilators were judged not to suffer from OAD. CONCLUSIONS: Office spirometry added significantly more to the diagnostic certainty of the GPs than questionnaires, history and clinical examination. A pulmonologist's advice contributed more to diagnostic certainty than any other diagnostic step. Nevertheless, 26% of the diagnoses made by the chest physicians were reconsidered by the GPs. PMID- 22094828 TI - Lung function changes in non-asthmatic allergic rhinitis patients: a case series. PMID- 22094826 TI - Care of the infant of the diabetic mother. AB - Gestational diabetes mellitus (GDM) from all causes of diabetes is the most common medical complication of pregnancy and is increasing in incidence, particularly as type 2 diabetes continues to increase worldwide. Despite advances in perinatal care, infants of diabetic mothers (IDMs) remain at risk for a multitude of physiologic, metabolic, and congenital complications such as preterm birth, macrosomia, asphyxia, respiratory distress, hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia and hyperviscosity, hypertrophic cardiomyopathy, and congenital anomalies, particularly of the central nervous system. Overt type 1 diabetes around conception produces marked risk of embryopathy (neural tube defects, cardiac defects, caudal regression syndrome), whereas later in gestation, severe and unstable type 1 maternal diabetes carries a higher risk of intrauterine growth restriction, asphyxia, and fetal death. IDMs born to mothers with type 2 diabetes are more commonly obese (macrosomic) with milder conditions of the common problems found in IDMs. IDMs from all causes of GDM also are predisposed to later-life risk of obesity, diabetes, and cardiovascular disease. Care of the IDM neonate needs to focus on ensuring adequate cardiorespiratory adaptation at birth, possible birth injuries, maintenance of normal glucose metabolism, and close observation for polycythemia, hyperbilirubinemia, and feeding intolerance. PMID- 22094829 TI - Complementation of Sulfolobus solfataricus PBL2025 with an alpha-mannosidase: effects on surface attachment and biofilm formation. AB - Compared to Sulfolobus solfataricus P2, the S. solfataricus mutant PBL2025 misses 50 genes (SSO3004-3050), including genes coding for a multitude of enzymes possibly involved in sugar degradation or metabolism. We complemented PBL2025 with two of the missing proteins, the alpha-mannosidase (SSO3006, Ssalpha-man) and the beta-galactosidase LacS (SSO3019), and performed comparative fluorescence microscopy and confocal laser scanning microscopy to analyze the recombinant strains. We demonstrated that the Ssalpha-man complemented strain resembled the S. solfataricus P2 behavior with respect to attachment of cells to glass and growth of cells in static biofilms. During expression of the Ssalpha-man, but not LacS, glucose and mannose-containing extracellular polymeric substance (EPS) levels changed in the recombinant strain during surface attachment and biofilm formation. These results suggest that the Ssalpha-man might be involved in the modulation of the EPS composition and/or in the de-mannosylation of the glycan tree, which is attached to extracellular glycosylated proteins in S. solfataricus. On the other hand, LacS expression in PBL2025 reduced the carbohydrate content of the isolated total EPS implying a role in the modulation of the produced EPS during static biofilm formation. These are the first enzymes identified as playing a role in archaeal EPS formation. PMID- 22094833 TI - Iodine excess or not: analysis on the necessity of reducing the iodine content in edible salt based on the national monitoring results. AB - Using national monitoring data collected between 1995 and 2009, this paper describes the change in trend with regard to the coverage of qualified iodized household salt and iodine status of the population in China since the implementation of universal salt iodization. The review indicates that the iodine content in edible salt increased from 16.2 mg/kg in 1995 to 42.3 mg/kg in 1999, then declined to 30.8 mg/kg in 2005 and has retained this level through the most recent data collection cycle, which is considered sufficient to achieve optimal iodine status. However, the median urinary iodine excretion level for children aged 8-10 at the national level has been consistently classified as "excessive iodine intake" since 1997, suggesting that although three adjustments on the standard of iodine content in edible salt have been made, the current content of salt iodization is still on the high side. The iodine content in edible salt could be lowered, and possibly adapted to local specific conditions such as water iodine content and the average daily intake of salt among the population in order to achieve a balance between preventing deficiency and reducing the risk of excessive intake. PMID- 22094831 TI - Tungsten-induced denaturation and aggregation of epoetin alfa during primary packaging as a cause of immunogenicity. AB - PURPOSE: Following two cases of neutralizing antibodies to epoetin alfa in an investigational clinical study, a small number of individual syringes of two drug product batches were found to contain unusually high levels of aggregation at the end of the clinical trial. METHODS: We undertook an extensive analytical approach to determine the root-cause of the increased aggregation in the affected batches. RESULTS: Soluble tungsten was found in the syringes, most likely derived from the pins used to manufacture the syringes. Spiking of epoetin alfa with sodium polytungstate or an extract of tungsten pins used to manufacture the syringes induced the formation of aggregates, both dimers that appeared to be covalently linked by disulphide bonds as well as higher-order aggregates. Sodium polytungstate had also a strong denaturing effect on the protein. CONCLUSIONS: We propose tungsten-mediated unfolding and aggregation of epoetin alfa in pre-filled syringes as a potential root cause for increased immunogenicity. This finding may be more broadly applicable to this and other classes of therapeutic proteins. PMID- 22094834 TI - Association between 24 hour urinary alpha-tocopherol catabolite, 2,5,7,8 tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and alpha-tocopherol intake in intervention and cross-sectional studies. AB - The objective is to determine the association between the 24 hour urinary alpha tocopherol catabolite, 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and alpha-tocopherol intake in an intervention and a cross-sectional studies. In the 4-weeks intervention study, Japanese men (n = 10) consumed the test diet in week 1, and the test diet plus varying amounts of alpha-tocopherol in the three subsequent weeks: 21 MUmol/d alpha-tocopherol in week 2, 63 MUmol/d in week 3, and 125 MUmol/d in week 4. A significant association between alpha tocopherol intake and urinary alpha-CEHC was observed in this strictly controlled experiment (r = 0.99, p<0.001). In the cross-sectional study, all foods consumed over 4 consecutive days were recorded in 76 free-living young subjects (18-33 years). The association was weak, but a significant relationship was observed (r = 0.29, p<0.05) even in the cross-sectional study. In the cross-sectional study adults, mean estimated alpha-tocopherol intake calculated by urinary alpha-CEHC and the excretory ratio was 91% of their mean intake over the 4 days. The results show that urinary alpha-CEHC level reflected recent alpha-tocopherol intake in free-living young Japanese adults, and could be used as a measure of intake during the previous few days, both for group means and for individual rankings within a group. PMID- 22094835 TI - Moderate NaFeEDTA and ferrous sulfate supplementation can improve both hematologic status and oxidative stress in anemic pregnant women. AB - Iron is important general well being, to prevent or treat anemia, and is a cofactor of many enzymes in the anti-oxidant process. Effect of sodium iron ethylenediaminetetraacetate (NaFeEDTA) and ferrous sulfate on iron bioavailability and oxidative stress in anemic pregnant women was evaluated. A 2 month randomized controlled trial was conducted on 153 anemic pregnant women, with 80 <= Hb <110 g/L. They were randomly allocated to three groups: group C (n=51) was the placebo control group, group I (n=51) was supplemented daily with 60 mg iron as ferrous sulfate, and group IE (n=51) with 60 mg iron as NaFeEDTA. Blood samples were collected before and at the end of the intervention for measurements of hematological indices and oxidative stress parameters. Considerable increases of hematologic indicators were observed: 20.5 and 21.8 g/L for Hb (both p values <0.001); 4.81 and 7.19 MUmol/L for plasma iron (both p values <0.001), 2.63 and 8.99 MUg /L for ferritin (both p values <0.05) in I and IE groups, respectively, compared with the control group. Glutathione peroxidase (GSH-Px) activities increased by 32.6 and 75.3 IU/ml, and malondialdehyde (MDA) levels decreased by 0.70 and 1.12 MUmol/L in I and IE groups, compared with the C group (p values <0.05). Moreover, differences of plasma iron, ferritin and GSH-Px activity were 2.38 MUmol/L, 6.36 MUg /L and 42.7 IU/ml were also significantly greater in the IE group than in the I group. Moderate iron supplementation may be beneficial to improving iron deficiency and oxidative stress, and NaFeEDTA is better than ferrous sulfate. PMID- 22094836 TI - Impact of treatment with oral calcitriol on glucose indices in type 2 diabetes mellitus patients. AB - INTRODUCTION: Type 2 diabetes is a major public health problem. Recent epidemiological evidence also points to a potential association of vitamin D insufficiency with adverse metabolic risks, including that for type 2 diabetes. SUBJECTS AND METHOD: A double-blind randomized placebo-controlled trial was carried out. Seventy subjects with type 2 diabetes, age 30-75 years old, were randomly assigned in a double-blind fashion to two groups. One group received two capsules of calcitriol (0.25 MUg 1,25-dihydroxy cholecalciferol per each capsule) per day. The second group received placebo tablets. At the beginning, middle and the end of the 12 week supplementation trial, serum glucose, insulin, calcium and phosphorous, HbA1c and 25(OH) vitamin D were measured. RESULTS: There was no significant difference between two groups at baseline. At the end of the study, fasting plasma glucose increased in the control group (p=0.038), while it remained unchanged in calcitriol group. Level of insulin and HbA1c increased significantly in both groups (p=0.013 and 0.0004 in treatment and control group). Regarding insulin resistance indices, there was a significant change in HOMA-IR and QUICKI in both groups (p=0.023 and 0.002 in treatment and 0.001 and <0.001 in control group respectively). Insulin secretion as assessed by HOMA-%beta, remained relatively unchanged in the control group, while it increased significantly in the treatment group at the end of study (p=0.009). CONCLUSION: Vitamin D supplementation attenuated the increase in glycemia, and increased insulin secretion, but had no effect on insulin resistance. PMID- 22094837 TI - Acute effect of a soy protein-rich meal-replacement application on renal parameters in patients with the metabolic syndrome. AB - BACKGROUND: Soy protein is used for meal replacement therapy in obesity, however the influence on renal function parameters is not adequately investigated. This study evaluates glomerular filtration rate (GFR) and renal plasma flow (RPF) in patients with the metabolic syndrome and healthy controls after ingestion of different amounts of soy protein. METHODS: 10 patients with the metabolic syndrome but no signs of kidney disease and 10 healthy controls ingested 1 g protein/kg body weight of a commercial soy-yoghurt-honeypreparation. The patient group was also given a protein challenge of 0.3 g/kg body weight. RESULTS: Baseline GFR and RPF both were significantly higher in the patient group (147 +/- 34.8 vs. 116 +/- 21.1 ml/min, p=0.01 and 848 +/- 217 vs. 637 +/- 121 ml/min, p=0.02) and were strongly correlated with body weight. Use of different algorithms to estimate GFR resulted in underestimation of GFR, particularly in the patients with the metabolic syndrome. The challenge with an acute protein load of 1g protein per kilogram body weight induced a significant increase in GFR and RPF in healthy controls (GFR: +12.6 +/- 11.0 % (p=0.01), RPF: +13.6 +/- 15.6 % (p=0.04)) and even more in patients with the metabolic syndrome (GFR: +31.5 +/- 32.2 % (p=0.01); RPF: +19.4 +/- 22.7 % (p=0.02)). The ingestion of 0.3 g protein/ kg body weight did not induce significant changes. CONCLUSIONS: Basic renal function is changed in patients with the metabolic syndrome, even without microalbuminuria. In addition, there is an elevated susceptibility for protein load. However, the protein amount recommended for use in soy-protein based meal replacement therapy induced no significant changes. PMID- 22094838 TI - Fortified juice drink improved iron and zinc status of schoolchildren. AB - Energy and micronutrient deficiency remain prevalent among Filipino children. Juice drinks are commonly consumed and could be a viable vehicle for fortification to supplement the nutrient gap. This study determined the effects of a newly developed non-carbonated fortified juice drink on the iron, zinc and nutritional status of schoolchildren. One hundred randomly selected anemic children were randomly allocated into two groups in a doubly-masked placebo controlled manner: Group 1 received the fortified juice, Group 2 received the non fortified juice for 100 days, five days a week under strict supervision. The juice drink was fortified with vitamin A, zinc, iron, vitamin C and lysine. The non-fortified juice was fortified only with vitamin C. All children were dewormed prior to the intervention. Hemoglobin, plasma ferritin and plasma zinc, weight and height were assessed using standard methods before and after intervention. A two-day 24-hour food recall was also collected. The basal prevalence of anemia was significantly reduced in both the fortified group (100% to 13%) and the non fortified group (100% to 40%) at endline. The mean plasma ferritin levels were similar in both groups at baseline and endline. At endline, mean plasma zinc in the fortified group has significantly increased by 20 MUg/dL from a baseline value of 83.9 MUg/dL to 103.9 MUg/dL, while the non-fortified group remained at similar levels with baseline. Basal weight and height significantly increased among all children at endline. The fortified juice drink was effective in reducing the prevalence of anemia and improved the zinc status of children. PMID- 22094839 TI - Malnutrition in hospitalized people living with HIV/AIDS: evidence from a cross sectional study from Chengdu, China. AB - OBJECTIVES: Nutrition support has long been ignored in China's HIV/AIDS treatment and care. The objectives of this project were to evaluate the prevalence of malnutrition among Chengdu urban HIV positive patients, and to provide evidence for further nutritional intervention. MATERIALS AND METHODS: HIV-infected adults admitted to an infectious diseases inpatient unit were eligible for this study. Nutritional status was evaluated using Subject Global Assessment (SGA), Malnutrition Universal Screening Tool (MUST), body mass index (BMI), food frequency questionnaire and dietary records. RESULTS: 94 hospitalized HIV positive patients were enrolled from April 2009 to May 2010. The median CD4 T cell count was 44.0/mm3. The prevalence of malnutrition is measured by three tools and ranged from 37.2% (by BMI) to 77.2% (by SGA class B/C or MUST scores >= 2). Chi-square test showed significant relationship between opportunistic infections and MUST score (OR=5.67, p<0.005, 95% CI=1.96-16.4). Of patients, 59.6% had insufficient total energy intake; while 54.3% had insufficient protein intake. CONCLUSIONS: Malnutrition is highly prevalent among Chengdu urban HIV/AIDS patients who underwent inpatient treatment. Calorie and protein deficiency should be given more attention in HIV/AIDS care programs. Nutrition evaluation and support should be considered an integral parts of national and community HIV/AIDS treatment and care guidelines. PMID- 22094840 TI - Anthropometric equation for estimation of appendicular skeletal muscle mass in Chinese adults. AB - The purpose of this study was to develop and cross-validate anthropometric equations for the estimation of appendicular skeletal muscle mass (ASM) in Chinese adults. A total of 763 adults aged 18-69 years (345 men and 418 women) were recruited from residents living in four regions (Jinan, Guangzhou, Xi'an and Chengdu) in China. ASM were measured by fan-beam dual energy x-ray absorptiometry. Participants' body weight, height, limb circumferences (upper arm, thigh, and calf), waist circumference, and skinfold thicknesses (triceps, thigh, and calf) were measured by trained testers. The participants were randomly assigned to two groups: a model-development group (MD group) and a cross validation group (CV group). Prediction models were established using the data from the MD group, and cross-validated with the data of the CV group. The results suggested that the developed equations had satisfactory prediction qualities, and could be applied as a practical method of quantifying ASM in Chinese adults. PMID- 22094841 TI - Waist circumference as an indicator of high blood pressure in preschool obese children. AB - OBJECTIVE: To investigate the relationship between waist circumference and blood pressure (BP) to determine if waist circumference was an indicator of BP in preschool children. METHODS: Body weight, height, waist circumference (WC), hip circumference, and blood pressure of 939 3-6-year-old preschool children were collected. RESULTS: Systolic blood pressure (SBP) and diastolic blood pressure (DBP) in obese children were significantly higher than that in normal weight children in both sexes (p<0.001). Overweight children had significantly higher SBP and DBP than normal weight boys (p<0.01). Age- and sex-adjusted Body mass index (BMI) correlated significantly with SBP and DBP. In children aged 3-6 years, age-, sex-and BMI-adjusted waist circumference correlated significantly with SBP, but not with DBP. Receiver operating characteristic (ROC) curves showed a significant ability of BMI, WC and waist-to-height ratio (WtHr) to discriminate high blood pressure in children of both sexes. Multiple linear stepwise regression analysis using SBP as the dependent variable showed that BMI and WC were significant independent factors that influence high blood pressure adjusted for age, WtHr and waist-to-hip circumference ratio (WHr) in boys. When using DBP as the dependent variable, BMI was the only significant independent factor that influenced high blood pressure adjusted for age, WtHr and WHr, in both sex-es. CONCLUSION: Waist circumference was independently associated with high blood pressure in boys aged 3-6 years. In addition to BMI, increased waist circumference was found to be an indicator of high blood pressure in the preschool children, especially in boys. PMID- 22094842 TI - Interactive effects of main genotype, caloric intakes, and smoking status on risk of obesity. AB - The aim of this study was to determine the strong candidate genes increasing susceptibility to obesity among previously reported obesity-related genes in Korean subjects and evaluate gene-environmental interactions in susceptibility to obesity. The study population comprised of 163 adolescents (95 boys and 68 girls) and their parents (97 men and 96 women).We used multivariable-adjusted logistic regression analysis, and classification and regression tree (CART) analysis incorporating both the genetic (ADRB2 R16G genotype) and environmental (overeating, smoking status, and parent's obese status) variables. The polymorphisms were genotyped with SNP-ITTM assays using the SNPstream 25KTM System (Orchid Biosciences, New Jersey, USA). Arg16 allele of ADRB2 R16G, smoking and overeating were linked to an increased risk of obesity in adults. CART analysis showed that smoking parents who overate and carried the Arg allele, ADRB2 R16G, had an odds ratio (OR) of 11.7 (95% confidence interval (CI), 2.13 64.04) for obesity compared to non-smoking parents who had none of these factors. Among children, the highest risk group for obesity was the overeater with obese parents (OR, 5.20; 95% CI, 1.86-14.53). The results of the study indicate that beta2-adrenoceptor polymorphism may contribute to the development of obesity through gene-environmental interactions. Further replication studies with larger sample size would be needed to confirm our study results. PMID- 22094843 TI - Contribution of complementary food nutrients to estimated total nutrient intakes for urban Guatemalan infants in the second semester of life. AB - Complementary foods (CF) are introduced earlier or later than appropriate in developing societies. They often contribute poorly to overall adequate micronutrient intake during the critical period for growth and development, which constitutes the period from 6 to 12 months of life. The objective of this study was to determine the contribution of the CF nutrients to the total estimated nutrient intake in infants in the second semester of life. Three non-consecutive 24-hour recalls interviews were conducted with mothers of 64 infants, aged 6-12 months on enrolment, from a convenience sample in a marginal urban settlement in Guatemala City. Retrospective recording of early introduction of pre- and post lacteal feeding and introduction of first foods and beverages was included. Human milk intakes were estimated by a model based on assumptions that human milk plus CF exactly satisfied the infant's daily energy needs. The WHO/FAO Recommended Nutrient Intakes (RNI) were the standards for adequate nutrient consumption. Instances of exclusive breast feeding to 6 months were rare, with the introduction of CF earlier than recommended. Baby food in jars was mentioned most frequently as the first food offered. The contribution of CF increased with age through the second semester of life. CF contributed more of a nutrient than human milk in all instances. However,CF nutrient density for Ca, Fe, and Zn fell below international standard. Fortified sugar contributed excessive amounts of Vitamin A to the diets. We conclude that for most nutrients, intakes reached or exceeded recommendation levels, unusual within the CF experience in scientific literature. PMID- 22094844 TI - Undernutrition status of children under 5 years in Chinese rural areas - data from the National Rural Children Growth Standard Survey, 2006. AB - PURPOSE: To assess the nutritional status among rural children under five years in China relative to WHO Child Growth Standards 2006, and to explore risk factors for undernutrition. DESIGN: Cross-sectional study of rural areas in 10 provinces of China. A total of 84,009 children under five recruited through multi-level sampling. MAIN FINDINGS: A total of 17.92% of children have at least one form of undernutrition. The prevalence of stunting, underweight and wasting, were 14.59%, 7.19% and 3.07%, respectively. The corresponding mean z-score in height-for-age, weight-for-age, and weight-for-height were -0.732, -0.410 and -0.001. An upward trend with age in stunting and underweight was observed, and higher risks noticed among older children in contrast with children under 6 months in terms of stunning and underweight. The inter-provincial variation of undernutrition remains very large. Low birth weight, multi parity, preterm birth, multiple birth, maternal illiteracy, low provincial GDP, and low household income are identified as significant factors associated with stunting. Parity shows no corresponding significant relationship with underweight, and wasting was not found to be associated with either preterm or multiple births. CONCLUSION: The nutritional status among children under five in rural areas of China, although greatly improved in the past decades, still lags behind the WHO Child Growth Standards. Stunting and underweight occur mostly before two years of age. Intervention strategies and programs should be developed to target the preventable risk factors. PMID- 22094845 TI - Systematic review and meta-analysis of soy products consumption in patients with type 2 diabetes mellitus. AB - Clinical trials have reported the lipid-lowering effect of consuming soy products, and epidemiological studies have shown that soy intake is associated with decreased risk of type 2 diabetes mellitus (T2DM). The aim of this meta analysis was to systematically review the effects of soy products consumption on serum lipid profiles and glycaemic control in T2DM patients. Potential papers were initially searched from PubMed (1966 to 2010) and Cochrane Library (1984 to 2010) without language limitations. All randomized controlled trials were included in which soy products supplementation was the only intervention in subjects with type 2 diabetes. Weighted mean effect size was calculated for net changes in serum lipids and fasting glucose concentrations using fixed-effect or random-effect models. Previously defined subgroup analyses were performed to identify the source of heterogeneity. Eight studies were included according to the criteria. The intake of soy products was associated with a significant reduction in serum total cholesterol (by 0.42 mmol/L; 95% confidence interval (CI): -0.70, -0.14; p<0.001), triacylglycerol (by 0.22 mmol/L; 95% CI: -0.38, 0.07; p<0.001) and low-density lipoprotein-cholesterol (by 0.30 mmol/L; 95% CI: 0.60, -0.00; p<0.001), and a significant increase in high-density lipoprotein cholesterol (0.05 mmol/L; 95% CI: 0.04, 0.06; p=0.89). There were no significant effects on fasting glucose, insulin and glycated hemoglobin. It can be concluded that intake of soy and soy products has beneficial effects in T2DM patients in relation to serum lipids. PMID- 22094846 TI - Red meat intake may increase the risk of colon cancer in Japanese, a population with relatively low red meat consumption. AB - Asian populations have changed from traditional to Westernized diets, with increased red meat intake. They are suggested to be particularly susceptible to the adverse effects of red meat on the development of colorectal cancers, however, few prospective studies of this putative link have been conducted. We examined associations between the consumption of red and processed meat and the risk of subsite-specific colorectal cancer by gender in a large Japanese cohort. During 1995-1998, a validated food frequency questionnaire was administered to 80,658 men and women aged 45-74 years. During 758,116 person-years of follow-up until the end of 2006, 1,145 cases of colorectal cancer were identified. Higher consumption of red meat was significantly associated with a higher risk of colon cancer among women [multivariate hazard ratios (95%CIs) for the highest versus lowest quintiles (HR): 1.48 (1.01, 2.17; trend p=0.03)], as was higher consumption of total meat among men [HR=1.44 (1.06, 1.98; trend p=0.07)]. By site, these positive associations were found for the risk of proximal colon cancer among women and for distal colon cancer among men. No association was found between the consumption of processed meat and risk of either colon or rectal cancer. In conclusion, red meat intake may modestly increase the risk of colon cancer in middle-aged Japanese, although the highest quintile of red meat consumption could be considered moderate by Western standards. PMID- 22094847 TI - Prevalence, influencing factors and control of food insecurity: a model in the northwest of Iran. AB - Food insecurity is frequent in both developed and developing countries, affecting from 5% to 25% of the general population. The aim of this study was to assess food insecurity, its influencing factors and control measures in the northwest of Iran. A total population of 15,070 (2,911 households) were studied. A short questionnaire was used for the screening of food insecurity and energy intake in this study. After the screening programme, those families identified as having food insecurity were recruited for the second part of the study which was a community trial. We organized small training campaigns (through peer education) for target households. Six months later, the same techniques were applied again to assess the impact of educational intervention in reducing the rate of food insecurity. Total prevalence of food insecurity in the study population was 59.3 percent (95% confidence interval: 57.4-61.3). Logistic regression showed that apart from the mother's age and smoking status of the head of the family, there was a significant association between household food insecurity and other variables in the model (mainly economic factors). The prevalence of food insecurity reduced by 7.3 percent after the intervention (p>0.10). The high prevalence of food insecurity in this study indicates that there is an urgent need for a close collaboration between governmental, international and local leadership to identify and implement the key interventional programmes to overcome this ever increasing health problem. According to our findings, a special attention should be paid on the economic improvement in the region. PMID- 22094848 TI - Paternal smoking is associated with greater food insecurity among poor families in rural Indonesia. AB - Food insecurity is common in developing countries and related to the physical well being of families. Household food insecurity is intended to reflect a household's access, availability, and utilization of food. The relationship between paternal smoking and household food insecurity has not been well characterized. The objective of this study was to examine the relationship of paternal smoking with household food insecurity among poor families in rural Indonesia. In a cross-sectional study of 26,380 rural households in the Indonesian Nutrition Surveillance System in 2003, we examined the relationship between paternal smoking and household food insecurity score, as measured using a 9-item food security questionnaire. The prevalence of paternal smoking was 72.9%. In families with and without a father who smoked, the mean (standard error) household food insecurity score was 1.83 (0.01) and 1.48 (0.02), respectively (p<0.0001). Paternal smoking was associated with greater household food insecurity score (p<0.0001) in a multivariable linear regression model, adjusting for maternal age, maternal education, weekly household expenditure per capita, and province. Among poor families in rural Indonesia, households with a father who smokes are at greater risk of household food insecurity. PMID- 22094849 TI - Comparison of dietary habits between migrant and local adolescents in Shenzhen, China. AB - BACKGROUND: It is estimated that the number of migrant adolescents in Chinese cities may have reached 25 million. However, little research has been conducted on their dietary habits. The objective of this study was to compare dietary habits between migrant and local adolescents in Shenzhen, China. METHODS: A school based cross-sectional study was conducted in 3368 adolescents (aged 11-18 years; 52.5% boys). A self-administered questionnaire completed by adolescents was designed to gather information on socio-demographic characteristics, meal location, food pattern and intake. RESULTS: Of the 3368 adolescents, 58.2% were migrants. Compared with locals, migrant adolescents showed significantly higher percentage of having three meals away-from home. Nearly half of the subjects (45.6 %) skipped breakfast, with a higher proportion among migrant students (48.5 vs 41.5%). Migrant students consumed street food more frequently (12.2 vs 8.5%), while the difference was opposite in Western fast food intake (27.3 vs 32.5%). No significant difference was found in snacks intake between these two groups. Migrant students exhibited lower percentage of vegetables (57.3 vs 63.7%), fruits (27.7 vs 38.3%), meats (37.0 vs 44.3%), soybean (11.6 vs 17.5%) and dairy products (28.4 vs 42.5%) intake daily. After adjusted for socio-demographic confounders, the difference mentioned above still remained except Western fast food. CONCLUSION: Dietary habits among adolescents showed pronounced household variation. Migrant adolescents are more likely to exhibit unhealthy dietary behavior. Schools and families should collaborate to improve the dietary environment for adolescents, especially those from migrant families. PMID- 22094850 TI - Nutrition risk: cultural aspects of assessment. AB - AIM: To assess a nutrition risk screening tool amongst Maori and non-Maori of advanced age. METHOD: A cross sectional feasibility study was conducted in three North Island locations. One hundred and eight community-living residents aged 75- 85 years were assessed for nutrition risk using 'the validated questionnaire 'Seniors in the Community: Risk Evaluation for Eating and Nutrition', Version II (SCREENII) and level of physical activity using the 'Physical Activity Scale for the Elderly' (PASE). Physical assessments included height and weight. RESULTS: Fifty-two percent of participants were assessed to be at high nutrition risk (SCREENII score <50; range 29-58; out of maximum score 64). Nutrition risk factors amongst Maori and non-Maori respectively differed for weight change in the previous six months (45.2% and 18.7%, p=0.005), skipping meals (54.8% and 13.3%, p<0.001), fruit and vegetable intake (77.4% and 18.7%, p<0.001) and the use of meal replacements (28.1% and 9.3%, p=0.013). Process evaluation showed that Maori took different meaning from the individual question items in SCREENII. Level of physical activity (PASE score) was higher for Maori, median (IQR): 125 (74) than non-Maori, 72 (74) (p<0.001) especially for leisure-time and household related activity. BMI was higher for Maori median (IQR): 31.5 kg/m2 (6.8) compared to non-Maori 24.7 kg/m2 (5.4) (p<0.001). CONCLUSIONS: The nutrition risk tool suggested that Maori were at high risk for malnutrition despite higher BMI and higher levels of activity. Several items of the screening tool were interpreted differently among Maori compared to non-Maori. Further development is needed to ensure accurate assessment. PMID- 22094851 TI - Validation of a food frequency questionnaire to assess dietary cholesterol, total fat and different types of fat intakes among Malay adults. AB - BACKGROUND: Cardiovascular diseases are the major cause of death in Malaysia. Evidence shows that dietary fat intake is one of the important risk factors for cardiovascular disease. However, studies assessing the association of fatty acids and risk of cardiovascular diseases in Malaysia are scarce. Therefore, this study aimed to develop and validate a food frequency questionnaire (FFQ) assessing total fat and different types of fat among Malay adults in Malaysia. METHODS: A 100 food item FFQ focused on dietary cholesterol, total fat, saturated fat, monounsaturated fat and polyunsaturated fat intake for the past one month was developed and validated against 3-day dietary record (DR) among 151 Malay participants. Validity was assessed through the reliability and agreement of two methods. Intra-class correlation (ICC) coefficients were used to assess reliability; while regression analysis and classification into categories were used to assess agreement of the two methods. RESULTS: The mean nutrient intakes tended to be higher in FFQ compared to DR. The developed FFQ showed excellent reliability with ICC coefficients ranging from 0.92-0.98. Regression analysis demonstrated an acceptable agreement between FFQ and DR for total fat and different types of fat intakes. There were a relatively high proportion of subjects being correctly classified (into same or adjacent category) and only a small number of grossly misclassification for total energy, fat, dietary cholesterol, saturated fat and unsaturated fat occurred. CONCLUSION: This FFQ is valid in assessing absolute total energy, total fat and types of fat intakes among Malay adults. PMID- 22094852 TI - Validity of predictive equations for resting energy expenditure among Iranian women. AB - OBJECTIVES: To determine the resting metabolic rate (RMR) in a sample of Iranian women, and to evaluate the validity of predictive equations for estimating RMR in normal and obese subjects. METHODS: This cross-sectional study was conducted on a total of 187 healthy women aged 18-45 years. Anthropometric data were collected and subjects' RMR was measured by indirect calorimetry for 15 minutes following an overnight fast. RMR was also predicted using various types of formulas based on subjects' height, age, weight or fat-free mass. Body composition was estimated by bioelectric impedance analysis (BIA). RESULTS: Measured RMR (mean +/- SD) was found to be 1473 +/- 296 kcal/day. The abbreviation formula overestimated RMR, while other formulas underestimated it. Harris-Benedict formula was valid among all BMI categories (normal weight, overweight, obese and morbidly obese). Two Schofield formulas were valid in normal weight, overweight and morbidly obese subjects; and Cunningham formula was valid only among overweight and obese women. Overweight and obese Iranian women had higher RMR in comparison with normal weight subjects (p<0.01); although after age and weight adjustment, the differences were not significant in any of the BMI categories. CONCLUSIONS: The Harris-Benedict for mula provides a valid estimation of RMR at the group level in a range of normal-weight to morbidly obese Iranians. However, at the individual level, errors might be so high that using a measured value has to be preferred over an estimated value. PMID- 22094853 TI - Development of a borondipyrromethene-based Zn2+ fluorescent probe: solvent effects on modulation sensing ability. AB - A borondipyrromethene-based Zn(2+) fluorescent probe BODPAQ was designed and synthesized. The chelators in BODPAQ, 2,2'-dipicolylamine (DPA) and 8 aminoquinoline (AQ), coordinate to Zn(2+) in a synergic manner. As a result, BODPAQ displays high Zn(2+) selectivity with a dramatic enhanced emission accompanied by a notable hypsochromic shift due to the binary inhibition effect of PET and ICT mechanisms, enabling the detection of Zn(2+) by both ratiometric and normal turn-on fluorescence methods in acetonitrile. Interestingly, the sensitivity of BODPAQ towards Zn(2+) changes upon varying the compositions of buffer solutions. In 3-morpholinopropanesulfonic acid (MOPS) buffer aqueous solution (50% CH(3)CN), BODPAQ displays the highest sensitivity for Zn(2+), while in citrate-phosphate buffer, BODPAQ shows no response to Zn(2+). PMID- 22094854 TI - Hearing profile of gold miners with and without tuberculosis. AB - OBJECTIVES: To compare the hearing of gold miners with and without tuberculosis (TB) to determine the effect of TB and its associated risk profile on hearing. METHODS: Audiological and medical surveillance data of 2698 South African gold miners for 2001-2009 were analysed in a retrospective cohort design. Hearing thresholds for the air conduction frequencies (0.5, 1, 2, 3, 4, 6, 8 kHz) in both ears were analysed together with biographical and occupational data. Subjects were divided into two experimental (single TB treatment, n=911 and multiple TB treatment, n=376) and one control group (n=1411). Comparisons between groups included (1) change from baseline to most recent audiogram, (2) most recent hearing thresholds and (3) most recent thresholds in a subset of noise exposed and unexposed groups. RESULTS: Hearing thresholds for the TB groups were significantly (p<0.01) elevated compared to the control group, after correcting for time between baseline and most recent audiogram, threshold at baseline and age at test. Pair-wise comparisons demonstrated the largest threshold differences between the control and multiple TB group. Changes in mean thresholds across TB treatment groups were independent of noise exposure. Hearing thresholds over time also deteriorated significantly more (p<0.01) in workers with TB (single and multiple treatment) than in workers without TB. CONCLUSION: Gold miners with TB, especially with more than one episode of TB, demonstrate significantly poorer hearing thresholds and more pronounced decline in hearing over time independent of noise exposure. The exact cause is likely a complex interaction between TB, including treatment, and its associated risk profile. PMID- 22094855 TI - Immediate ozone effects on heart rate and repolarisation parameters in potentially susceptible individuals. AB - OBJECTIVES: Elevated ozone levels have been associated with cardiovascular morbidity and mortality. We investigated the effects of ozone on heart rate (HR) and repolarisation parameters in potentially susceptible populations. METHODS: Between March 2007 and December 2008, 363 ECG recordings including >2000 1 h intervals were measured in 64 individuals with type 2 diabetes or impaired glucose tolerance and in 46 healthy individuals with a potential genetic predisposition on the detoxification pathways from Augsburg, Germany. Associations between 1 h averages of ozone and HR, Bazett-corrected QT-interval (QTc), T-wave amplitude and T-wave complexity were analysed using additive mixed models. A variable indicating season and participants' location during the 1 h ECG recordings (summer and outdoors vs winter or indoors) was used as a potential ozone effect modifier. RESULTS: We observed concurrent and 1-4 h lagged increases in HR of 0.5-0.7% for each 20 MUg/m(3) increase in ozone. These effects were stronger (1.0-1.2%) when participants were outdoors during the summer. We detected in all participants a concurrent (-1.31%; 95% CI -2.19% to -0.42%) and 1 h lagged (-1.32%; -2.19% to -0.45%) T-wave flattening. Elevated ozone levels were associated with 1 h (2.12%; 0.81 to 3.52) and 2 h lagged (1.89%; 0.55% to 3.26%) increases in T-wave complexity. However, no effects were seen for QTc. Ozone effects were generally more pronounced in individuals with metabolic disorders than a potential genetic predisposition. CONCLUSIONS: Changes in repolarisation might contribute to underlying pathophysiological changes associated with the link between elevated ozone levels and reported adverse cardiovascular outcomes. PMID- 22094856 TI - Association of the HLA-DRB1 epitope LA(67, 74) with rheumatoid arthritis and citrullinated vimentin binding. AB - OBJECTIVE: Although rheumatoid arthritis (RA) has long been associated with an HLA-DRB1 shared epitope, a systematic search for other epitopes has never been conducted. In addition, the relationship between these epitopes and the binding of citrullinated autoantigens has not been investigated. We developed a program that can analyze HLA data for all possible epitopes of up to 5 amino acids and used this program to assess the shared epitope hypothesis in RA. METHODS: We analyzed high-resolution data from the International Histocompatibility Working Group, which included a group of 488 patients with RA and a group of 448 racially and ethnically balanced control subjects, for all combinations of up to 5 amino acids among polymorphic HLA-DRB1 positions 8-93. Statistical significance was determined by chi-square and Fisher's exact tests, with a false discovery rate correction. RESULTS: Three residues (V(11), H(13), and L(67)) were found to have the highest degree of association with RA susceptibility (P < 10(-11)), and D(70) was found to correlate best with RA resistance (P = 2 * 10(-11)). Of >2 million epitopes examined, LA(67, 74) exhibited the highest correlation with RA susceptibility (P = 2 * 10(-20); odds ratio 4.07 [95% confidence interval 3.07 5.39]). HLA alleles containing the LA(67, 74) epitope exhibited significantly greater binding to citrullinated vimentin(65-77) than did alleles containing D(70). Only 1 allele (DRB1*16:02) contained both LA(67, 74) and D(70); it bound citrullinated vimentin weakly and was not associated with RA. CONCLUSION: The findings of these studies confirm the importance of HLA-DRB1 amino acids in pocket 4 for the binding of citrullinated autoantigens and susceptibility to RA. PMID- 22094857 TI - Isolating metamemory deficits in the self-regulated learning of adults with ADHD. AB - ADHD in adulthood is associated with chronic academic impairments and problems with strategic memory encoding on standardized memory assessments, but little is known about self-regulated learning that might guide intervention. OBJECTIVE: Examine the contribution of metamemory judgment accuracy and use of learning strategies to self-regulated learning in adults with ADHD, focusing on the use of self-testing. METHOD: A total of 34 adults with ADHD and 34 matched controls predicted their memory performance and regulated their learning of paired associates. RESULTS: Adults with ADHD were as accurate as controls at predicting memory performance, despite remembering fewer words. By observation and self report, they were less likely to use self-testing to learn the pairs. CONCLUSION: Across groups, self-testing was associated with significantly better recall and largely accounted for differences between diagnostic groups. Adults with ADHD often failed to employ a strategy that was associated with improved memory, identifying an intervention target that may improve self-regulated learning. PMID- 22094858 TI - Factor analysis of five adult ADHD self-report measures: are they all the same? AB - OBJECTIVE: To test the assumption in the research and assessment of ADHD symptoms that self-report scales measure the same underlying cognitive construct and that there is convergent validity among the scales. The present study specifically tested this assumption by analyzing the scores of 616 individuals on five ADHD self-rating scales using principal components analysis. METHOD: Participants completed five self-report scales widely used in the clinical and research communities: the CSS, the BADDS, the CAARS, the AADDES, and the WURS. RESULTS: Results show that while all scales were highly correlated and loaded onto a single factor solution, the WURS was differentiated from the other four scales best seen through a two factor solution. Therefore, the WURS may also measure other mental and emotional constructs independent from ADHD. Furthermore, participants that reported a previous diagnosis of ADHD scored significantly higher on all measures than those who did not. CONCLUSION: Since these scales are in strong agreement with one another in diagnosing ADHD, assessment becomes an issue of which scale is the least time-consuming and most pragmatic for the evaluator to use. PMID- 22094859 TI - Genome economization in the endosymbiont of the wood roach Cryptocercus punctulatus due to drastic loss of amino acid synthesis capabilities. AB - Cockroaches (Blattaria: Dictyoptera) harbor the endosymbiont Blattabacterium sp. in their abdominal fat body. This endosymbiont is involved in nitrogen recycling and amino acid provision to its host. In this study, the genome of Blattabacterium sp. of Cryptocercus punctulatus (BCpu) was sequenced and compared with those of the symbionts of Blattella germanica and Periplaneta americana, BBge and BPam, respectively. The BCpu genome consists of a chromosome of 605.7 kb and a plasmid of 3.8 kb and is therefore approximately 31 kb smaller than the other two aforementioned genomes. The size reduction is due to the loss of 55 genes, 23 of which belong to biosynthetic pathways for amino acids. The pathways for the production of tryptophan, leucine, isoleucine/threonine/valine, methionine, and cysteine have been completely lost. Additionally, the genes for the enzymes catalyzing the last steps of arginine and lysine biosynthesis, argH and lysA, were found to be missing and pseudogenized, respectively. These gene losses render BCpu auxotrophic for nine amino acids more than those corresponding to BBge and BPam. BCpu has also lost capacities for sulfate reduction, production of heme groups, as well as genes for several other unlinked metabolic processes, and genes present in BBge and BPam in duplicates. Amino acids and cofactors that are not synthesized by BCpu are either produced in abundance by hindgut microbiota or are provisioned via a copious diet of dampwood colonized by putrefying microbiota, supplying host and Blattabacterium symbiont with the necessary nutrients and thus permitting genome economization of BCpu. PMID- 22094860 TI - Random Addition Concatenation Analysis: a novel approach to the exploration of phylogenomic signal reveals strong agreement between core and shell genomic partitions in the cyanobacteria. AB - Recent whole-genome approaches to microbial phylogeny have emphasized partitioning genes into functional classes, often focusing on differences between a stable core of genes and a variable shell. To rigorously address the effects of partitioning and combining genes in genome-level analyses, we developed a novel technique called Random Addition Concatenation Analysis (RADICAL). RADICAL operates by sequentially concatenating randomly chosen gene partitions starting with a single-gene partition and ending with the entire genomic data set. A phylogenetic tree is built for every successive addition, and the entire process is repeated creating multiple random concatenation paths. The result is a library of trees representing a large variety of differently sized random gene partitions. This library can then be mined to identify unique topologies, assess overall agreement, and measure support for different trees. To evaluate RADICAL, we used 682 orthologous genes across 13 cyanobacterial genomes. Despite previous assertions of substantial differences between a core and a shell set of genes for this data set, RADICAL reveals the two partitions contain congruent phylogenetic signal. Substantial disagreement within the data set is limited to a few nodes and genes involved in metabolism, a functional group that is distributed evenly between the core and the shell partitions. We highlight numerous examples where RADICAL reveals aspects of phylogenetic behavior not evident by examining individual gene trees or a "'total evidence" tree. Our method also demonstrates that most emergent phylogenetic signal appears early in the concatenation process. The software is freely available at http://desalle.amnh.org. PMID- 22094862 TI - The orthodontist and sleep apnea. PMID- 22094863 TI - Lingual straightwire treatment with the Orapix system. PMID- 22094861 TI - Genome-wide detection of gene extinction in early mammalian evolution. AB - Detecting gene losses is a novel aspect of evolutionary genomics that has been made feasible by whole-genome sequencing. However, research to date has concentrated on elucidating evolutionary patterns of genomic components shared between species, rather than identifying disparities between genomes. In this study, we searched for gene losses in the lineage leading to eutherian mammals. First, as a pilot analysis, we selected five gene families (Wnt, Fgf, Tbx, TGFbeta, and Frizzled) for molecular phylogenetic analyses, and identified mammalian lineage-specific losses of Wnt11b, Tbx6L/VegT/tbx16, Nodal-related, ADMP1, ADMP2, Sizzled, and Crescent. Second, automated genome-wide phylogenetic screening was implemented based on this pilot analysis. As a result, we detected 147 chicken genes without eutherian orthologs, which resulted from 141 gene loss events. Our inventory contained a group of regulatory genes governing early embryonic axis formation, such as Noggins, and multiple members of the opsin and prolactin-releasing hormone receptor ("PRLHR") gene families. Our findings highlight the potential of genome-wide gene phylogeny ("phylome") analysis in detecting possible rearrangement of gene networks and the importance of identifying losses of ancestral genomic components in analyzing the molecular basis underlying phenotypic evolution. PMID- 22094864 TI - Early treatment of scissor bite. PMID- 22094865 TI - Surgical-orthodontic management of severe sleep apnea. PMID- 22094866 TI - Twisting ligature wires for lingual retainers. PMID- 22094867 TI - A microsensor for monitoring removable-appliance wear. PMID- 22094869 TI - Cardiovascular disorders: microRNA modulation elevates HDL. PMID- 22094868 TI - Exploring HCN channels as novel drug targets. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have a key role in the control of heart rate and neuronal excitability. Ivabradine is the first compound acting on HCN channels to be clinically approved for the treatment of angina pectoris. HCN channels may offer excellent opportunities for the development of novel anticonvulsant, anaesthetic and analgesic drugs. In support of this idea, some well-established drugs that act on the central nervous system including lamotrigine, gabapentin and propofol - have been found to modulate HCN channel function. This Review gives an up-to-date summary of compounds acting on HCN channels, and discusses strategies to further explore the potential of these channels for therapeutic intervention. PMID- 22094870 TI - Neurodegenerative diseases: An alternative path to reduce neuroinflammation. PMID- 22094871 TI - Analgesia: Unravelling epigenetic mechanisms of chronic pain. PMID- 22094872 TI - P27/SKP-2 histochemical profile is relevant to malignant salivary gland tumors (MST) histogenesis and tumor grade. AB - Malignant salivary gland tumors (MST) represent over more than 24 distinct morphological subtypes. Most high grade tumors arise from the excretory duct portion of the salivary gland apparatus; the remainder from the intercalated duct portion. Altered p27/skp-2 expression has been associated with tumor aggressiveness and histologic differentiation. In our study, we analyzed p27/skp 2 expression proteins on series of malignant salivary gland tumors in order to assess their value as a histogenetic marker, which is relevant to tumor grade. 61 MST cases were segregated by proposed histogenesis and immunohistochemistry was performed using antibodies directed against p27 and skp-2. MST of proposed intercalated duct origin (n=27) showed strong p27 expression (n=25/27; 93%) in the vast majority of cases and all cases weakly expressed skp-2. MST of proposed excretory duct origin (n=32) showed strong p27 expression (n=18/32; 56%) and moderately strong/strong skp-2 expression (n=18/32; 56%), respectively, in over half the cases. MST of intercalated duct origin showed evident p27/skp-2 inverse correlation. Differences in p27/skp-2 expression among the MST subtypes correlated with histogenesis and tumor grade, which reinforces the notion that tumor behavior is relevant to the portion of the salivary gland unit from which they arise. MST of proposed intercalated duct origin strongly expressed p27, and not skp-2, unlike MST of proposed excretory duct origin. The immunohistochemical profile of high grade mucoepidermoid carcinoma was distinct from its low/intermediate grade counterparts, suggesting a separate identity. These results may influence future decision making when formulating workable MST categorization schemes. Further studies on a larger series of MST are warranted in order to support the value of our findings. PMID- 22094873 TI - Bizarre parosteal osteochondromatous proliferation (Nora's Lesion) of the mandible. a rare bony lesion. AB - Bizarre parosteal osteochondromatous proliferation (BPOP) also eponymically called "Nora's lesion", is a rare benign reactive bone lesion first reported in 1983. BPOP occurs classically on the bones of the hands and feet and long bones. This lesion can easily be confused, both clinically and microscopically, with other benign and malignant lesions of bone, including osteochondroma, parosteal osteosarcoma, myositis ossificans and reactive periostitis. BPOP has been reported to have a high rate of recurrence. Only 3 cases of BPOP of the head and neck have been reported in the literature, of which one involved the maxilla. We present a rare case of BPOP involving the mandible in a 10 year old African American male. Microscopically, a fibro-cartilaginous cap giving rise to a proliferation of variably mineralized osteophytic finger-like projections of bone was seen. Multiple trabeculae of "blue bone" were noted as well as numerous atypical appearing chondrocytes. The lesion recurred within 4 months following the initial excision but has not recurred to date after the second local excision. To the best of our knowledge, this is the first report of BPOP arising in the mandible. In addition, we discuss the clinical and microscopic features, differential diagnosis, and prognosis of this rare entity. We present a case of BPOP of the mandible and believe this is the first report of such a case in the mandible. PMID- 22094874 TI - Mesenchymal stromal cell mutations and wound healing contribute to the etiology of desmoid tumors. AB - Desmoid tumors are nonmalignant neoplasms of mesenchymal origin that mainly contain fibroblast lineage cells. These tumors often occur in patients with familial adenomatous polyposis (FAP) coli who have germ line mutations in the APC gene. Given emerging data that has implicated multipotent mesencyhmal stromal cells (MSC) in the origin of mesenchymal tumors, we hypothesized that desmoid tumors may arise in patients with FAP after MSCs acquire somatic mutations during the proliferative phase of wound healing. To test this idea, we examined 16 desmoid tumors from FAP-associated and sporadic cases, finding that all 16 of 16 tumors expressed stem cell markers, whereas matching normal stromal tissues were uniformly negative. Desmoid tumors also contained a subclass of fibrocytes linked to wound healing, angiogenesis, and fibrosis. Using an MSC cell line derived from an FAP-associated desmoid tumor, we confirmed an expected loss in the expression of adenomatous polyposis coli (APC) and the transcriptional repressor BMI-1 while documenting the coexpression of markers for chondrocytes, adipocytes, and osteocytes. Together, our findings argue that desmoid tumors result from the growth of MSCs in a wound healing setting that is associated with deregulated Wnt signaling due to APC loss. The differentiation potential of these MSCs combined with expression of BMI-1, a transcriptional repressor downstream of Hedgehog and Notch signaling, suggests that desmoid tumors may respond to therapies targeting these pathways. PMID- 22094875 TI - ATM-mediated DNA damage signals mediate immune escape through integrin alphavbeta3-dependent mechanisms. AB - Although the tumor microenvironment plays a critical role in tumor progression and metastasis, the relationship between chemotherapy resistance and modulation of the tumor microenvironment remains unclear. Here, we report a novel mechanism showing how constitutive DNA damage signals in therapy-resistant tumor cells suppress antitumor immunity in an integrin-alphavbeta3-dependent manner. Integrin alphavbeta3 was upregulated on various therapy-resistant tumor cells through chronic activation of ATM/Chk2-and NFkappaB-mediated pathways. Inhibiting tumor specific expression of integrin-alphavbeta3 improved therapeutic responses to anticancer drugs by stimulating endogenous host immune systems. Mechanistic investigations revealed that tumor-specific integrin-alphavbeta3 expression targeted dendritic cells, facilitating their ability to phagocytose viable therapy-resistant tumor cells and thereby impaired their ability to cross-prime antigen-specific T lymphocytes. Together, our results clarify the detrimental effects of constitutive DNA damage signals to chemosensitivity and antitumor immunity. Furthermore, these findings suggest that integrin-alphavbeta3 targeting may benefit patients' refractory to current anticancer regimens by defeating DNA damage signaling-induced immune escape. PMID- 22094878 TI - Angiographic uterine artery chemoembolization followed by vacuum aspiration: an efficient and safe treatment for managing complicated cesarean scar pregnancy. AB - PURPOSE: To evaluate uterine artery chemoembolization (UAEC) followed by vacuum aspiration as a conservative treatment for complicated cesarean scar pregnancy. METHODS: A retrospective review was performed of women presenting with cesarean scar pregnancy between January 2002 and December 2008. The medical record was evaluated to determine the method of treatment. RESULTS: During the time period studied, 13 women were identified who underwent UAEC followed by vacuum aspiration. 12 women successfully had bilateral UAEC followed by vacuum aspiration alone, one woman had unilateral UAEC followed by vacuum aspiration but subsequently required laparotomy. All 13 women were successfully cured and retained uterus, there was no case with severe complicating disease. With the follow-up period, two women who were planning future pregnancy conceived, and spontaneous abortion occurred in one of them during the first trimester, another had an elective cesarean delivery at term. CONCLUSIONS: UAEC combined with vacuum aspiration is technically feasible and may help avoid laparotomy in women with cesarean scar pregnancy. PMID- 22094876 TI - Integrative genomic analyses of sporadic clear cell renal cell carcinoma define disease subtypes and potential new therapeutic targets. AB - Sporadic clear cell renal cell carcinoma (ccRCC), the most common type of adult kidney cancer, is often associated with genomic copy number aberrations on chromosomes 3p and 5q. Aberrations on chromosome 3p are associated with inactivation of the tumor suppressor gene von-Hippel Lindau (VHL), which activates the hypoxia-inducible factors HIF1alpha and HIF2alpha. In contrast, ccRCC genes on chromosome 5q remain to be defined. In this study, we conducted an integrated analysis of high-density copy number and gene expression data for 54 sporadic ccRCC tumors that identified the secreted glycoprotein STC2 (stanniocalcin 2) and the proteoglycan VCAN (versican) as potential 5q oncogenes in ccRCCs. In functional assays, STC2 and VCAN each promoted tumorigenesis by inhibiting cell death. Using the same approach, we also investigated the two VHL deficient subtypes of ccRCC, which express both HIF1alpha and HIF2alpha (H1H2) or only HIF2alpha (H2). This analysis revealed a distinct pattern of genomic aberrations in each group, with the H1H2 group displaying, on average, a more aberrant genome than the H2 group. Together our findings provide a significant advance in understanding ccRCCs by offering a molecular definition of two subtypes with distinct characteristics as well as two potential chromosome 5q oncogenes, the overexpression of which is sufficient to promote tumorigenesis by limiting cell death. PMID- 22094880 TI - Neurocircuitry involved in the development of alcohol addiction: the dopamine system and its access points. AB - The brain reward system, and especially the mesolimbic dopamine pathway, plays a major role in drug reinforcement and is most likely involved in the development of drug addiction. All major drugs of abuse, including ethanol, acutely activate the mesolimbic dopamine system. Both this acute drug-induced dopamine elevation, the dopamine elevations observed after presentations of drug-associated stimuli and alterations of dopamine function induced by chronic drug administration are of importance. Whereas the mechanisms of actions for central stimulants, opioids and nicotine in their dopamine activating effects are fairly well established, the corresponding mechanisms with respect to ethanol have been elusive. Here we review the actions of ethanol in the mesolimbic dopamine system, focusing on ethanol's interaction with ligand-gated ion-channel receptors, opiate receptors, the ghrelin system and the possible involvement of acetaldehyde. Preclinical studies have provided the opportunity to dissect these interactions in some detail and although we do not fully comprehend the actions of ethanol there have been some great advances resulting in increased knowledge of the complexity of ethanol's mechanism of action in this system. PMID- 22094879 TI - Investigating the deep supercooling ability of an Alaskan beetle, Cucujus clavipes puniceus, via high throughput proteomics. AB - Cucujus clavipes puniceus is a freeze avoiding beetle capable of surviving the long, extremely cold winters of the Interior of Alaska. Previous studies showed that some individuals typically supercool to mean values of approximately -40 degrees C, with some individuals supercooling to as low as -58 degrees C, but these non-deep supercooling (NDSC) individuals eventually freeze if temperatures drop below this. However, other larvae, especially if exposed to very cold temperatures, supercool even further. These deep supercooling (DSC) individuals do not freeze even if cooled to -100 degrees C. In addition, the body water of the DSC larvae vitrifies (turns to a glass) at glass transition temperatures of 58 to -70 degrees C. This study examines the proteomes of DSC and NDSC larvae to assess proteins that may contribute to or inhibit the DSC trait. Using high throughput proteomics, we identified 138 proteins and 513 Gene Ontology categories in the DSC group and 104 proteins and 573 GO categories in the NDSC group. GO categories enriched in DSC include alcohol metabolic process, cellular component morphogenesis, monosaccharide metabolic process, regulation of biological quality, extracellular region, structural molecule activity, and antioxidant activity. Proteins unique to DSC include alpha casein precursor, alpha-actinin, vimentin, tropomyosin, beta-lactoglobulin, immunoglobulins, tubulin, cuticle proteins and endothelins. PMID- 22094881 TI - Structural, functional and spectroscopic MRI studies of methamphetamine addiction. AB - This chapter reviews selected neuroimaging findings related to long-term amphetamine and methamphetamine (MA) use. An overview of structural and functional (fMRI) MR studies, Diffusion Tensor Imaging (DTI), Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) studies conducted in long-term MA abusers is presented. The focus of this chapter is to present the relevant studies as tools to understand brain changes following drug abstinence and recovery from addiction. The behavioral relevance of these neuroimaging studies is discussed as they relate to clinical symptoms and treatment. Within each imaging section this chapter includes a discussion of the relevant imaging studies as they relate to patterns of drug use (i.e., duration of MA use, cumulative lifetime dose and time MA abstinent) as well as an overview of studies that link the imaging findings to cognitive measures. In our conclusion we discuss some of the future directions of neuroimaging as it relates to the pathophysiology of addiction. PMID- 22094883 TI - Using FTIR spectroscopy to model alkaline pretreatment and enzymatic saccharification of six lignocellulosic biomasses. AB - Fourier transform infrared, attenuated total reflectance (FTIR-ATR) spectroscopy, combined with partial least squares (PLS) regression, accurately predicted solubilization of plant cell wall constituents and NaOH consumption through pretreatment, and overall sugar productions from combined pretreatment and enzymatic hydrolysis. PLS regression models were constructed by correlating FTIR spectra of six raw biomasses (two switchgrass cultivars, big bluestem grass, a low-impact, high-diversity mixture of prairie biomasses, mixed hardwood, and corn stover), plus alkali loading in pretreatment, to nine dependent variables: glucose, xylose, lignin, and total solids solubilized in pretreatment; NaOH consumed in pretreatment; and overall glucose and xylose conversions and yields from combined pretreatment and enzymatic hydrolysis. PLS models predicted the dependent variables with the following values of coefficient of determination for cross-validation (Q2): 0.86 for glucose, 0.90 for xylose, 0.79 for lignin, and 0.85 for total solids solubilized in pretreatment; 0.83 for alkali consumption; 0.93 for glucose conversion, 0.94 for xylose conversion, and 0.88 for glucose and xylose yields. The sugar yield models are noteworthy for their ability to predict overall saccharification through combined pretreatment and enzymatic hydrolysis per mass dry untreated solids without a priori knowledge of the composition of solids. All wavenumbers with significant variable-important-for-projection (VIP) scores have been attributed to chemical features of lignocellulose, demonstrating the models were based on real chemical information. These models suggest that PLS regression can be applied to FTIR-ATR spectra of raw biomasses to rapidly predict effects of pretreatment on solids and on subsequent enzymatic hydrolysis. PMID- 22094884 TI - Giant tumorous lesions (correction of legions) surrounding the right coronary artery associated with immunoglobulin-G4-related systemic disease. AB - Immunoglobulin G4 (IgG4)-related systemic disease was first recognized as a clinicopathological entity about 10 years ago, and since then, it has attracted growing attention. It is an autoimmune disease which affects multiple organs including the pancreas, bile duct, salivary glands and retroperitoneum. Further, it was recently reported that it can be manifested as periarteritis, often as inflammatory abdominal aortic aneurysm. We describe the case of a 75-year-old man with autoimmune pancreatitis and parotitis who presented with angina. The serum concentration of IgG4 was significantly increased at 2,510 mg/dl. Coronary angiography showed multiple stenotic lesions and pronounced dilatation of the right coronary artery. Cardiac computed tomography disclosed increased wall thickness of the coronary arteries and focal tumorous lesions surrounding the right coronary artery. Treatment with steroids proved only marginally effective and he underwent surgical resection of the aneurysm and coronary artery bypass grafting. The diagnosis of IgG4-related systemic disease was confirmed by histological examination of the resected mass, which showed a massive infiltration of IgG4-positive plasma cells. This case emphasizes the importance of considering the diagnosis in any patient with abnormally increased wall thickness or ectatic lesions in the coronary arteries. PMID- 22094885 TI - Fetal and neonatal diagnosis of interrupted aortic arch: associations and outcomes. AB - OBJECTIVE: Interrupted aortic arch (IAA) is a rare but serious anomaly. Prenatal diagnosis is challenging and published data are limited. The aim of the study was to review the data of fetuses and neonates diagnosed with IAA during a 16-year period at Children's Hospital Giessen. METHODS: Retrospective ascertainment of 8 fetuses and 20 neonates with a confirmed diagnosis of IAA from 1994 to 2010 by reviewing the hospital database of the cardiovascular program of the prenatal and pediatric cardiology clinics at the University Hospital Giessen. RESULTS: Eighteen cases with IAA type B and 10 cases with IAA type A were found. After 2005, prenatal diagnosis was achieved in 8 cases and postnatal imaging confirmed IAA in all 8 neonates. Twenty-nine percent of individuals had a chromosomal anomaly, with microdeletion 22q11.2 being the most common abnormality (n = 6, 21%). In 46% (13/28) other complex cardiac anomalies were present. Mortality after surgery was 18%. Long-term morbidity and mortality was due to neurological impairment in the presence of microdeletion 22q11.2 and the need of surgical or catheter re-intervention. CONCLUSION: Despite the difficulties and challenges in diagnosis, the prenatal detection rate of IAA is increasing. Associated complex cardiac and chromosomal abnormalities influence the outcome of patients with IAA and are important issues of parental counseling. PMID- 22094886 TI - Reliability of acute pancreatitis diagnosis coding in a National Patient Register: a validation study in Sweden. AB - AIM: National patient registers are powerful tools in epidemiological research and healthcare administration. As the level of reliability of diagnoses that are partly based on clinical signs, such as acute pancreatitis, may be low, the reliability of discharge diagnoses in these registers needs to be validated. The main aim of this study was to validate the diagnosis coding for acute pancreatitis in the Swedish National Patient Register. METHOD: We randomly sampled 650 admissions of all patients registered in the Swedish National Patient Register with acute pancreatitis or other nonmalignant pancreatic disorders as the main diagnosis in 2007 and 1998, and as the secondary diagnosis in 2007. The medical records for these admissions were reviewed. We analyzed the concordance between the coding of acute pancreatitis in the Swedish National Patient Register and criteria based on internationally accepted diagnostic standards. RESULTS: We received 603 medical records for manual review. Among the 530 patients with a diagnosis of acute pancreatitis in the Swedish National Patient Register, 442 (83%) were, after review, defined as definitive acute pancreatitis, 80 (15%) as probable acute pancreatitis, and 8 (2%) as no acute pancreatitis. There were no significant differences in the reliability of the diagnosis with regard to sex, age, time period or whether the patient had been treated at a county or university hospital. Among the 73 patients registered with a non-malignant pancreatic disorder other than acute pancreatitis, the number of false-negative cases of acute pancreatitis was 23 (32%). They were mainly found among patients registered with a diagnosis of chronic pancreatitis. CONCLUSION: The Swedish National Patient Register is highly reliable as regards correct coding of acute pancreatitis. However, there seems to be a non-negligible share of false-negative cases of acute pancreatitis among patients registered with a diagnosis of chronic pancreatitis. PMID- 22094888 TI - OEP80, an essential protein paralogous to the chloroplast protein translocation channel Toc75, exists as a 70-kD protein in the Arabidopsis thaliana chloroplast outer envelope. AB - Toc75 and OEP80 are paralogous proteins found in the Viridiplantae lineages, and appear to have evolved from a protein in the outer membrane of an ancient cyanobacterium. Toc75 is known to act as a protein translocation channel at the outer membrane of the chloroplast envelope, whereas the exact function of OEP80 is not understood. In Arabidopsis thaliana, each protein is encoded by a single gene, and both are essential for plant viability from embryonic stages onward. Sequence annotation and immunoblotting data with an antibody against its internal sequence (alphaOEP80(325-337)) indicated that the molecular weight of OEP80 is ca. 80 kD. Here we present multiple data to show that the size of A. thaliana OEP80 is smaller than previously estimated. First, we prepared the antibody against a recombinant protein consisting of annotated full-length A. thaliana OEP80 with an N-terminal hexahistidine tag (alphaOEP80(1-732)). This antibody recognized a 70-kD protein in the A. thaliana chloroplast membrane fraction which migrated faster than the His-tagged antigen and the protein recognized by the alphaOEP80(325-337) antibody on SDS-PAGE. Immunoprecipitation followed by LC MS/MS analysis confirmed that the 70-kD protein was encoded by the OEP80 cDNA. Next, we performed a genetic complementation assay using embryo-lethal oep80-null plants and constructs encoding OEP80 and its variants. The results revealed that the nucleotide sequence encoding the 52 N-terminal amino acids was not required for functional expression of OEP80 and accumulation of the 70-kD protein. The data also indicated that an additional C-terminal T7 tag remained intact without disrupting the functionality of OEP80, and was not exposed to the cytoplasmic surface of the chloroplast envelope. Finally, OEP80-T7 and Toc75 showed distinct migration patterns on blue native-PAGE. This study provides molecular tools to investigate the function of OEP80, and also calls for caution in using an anti peptide antibody. PMID- 22094887 TI - The lipopolysaccharide-induced pro-inflammatory response in RAW264.7 cells is attenuated by an unsaturated fatty acid-bovine serum albumin complex and enhanced by a saturated fatty acid-bovine serum albumin complex. AB - OBJECTIVE: A 1:1 ratio of fatty acid (FA)-albumin complex was chosen to mimic physiological conditions, and the effects of FA-bovine serum albumin (BSA) complexes were tested in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. METHODS: Nitric oxide (NO) and various proteins/factors in RAW264.7 cells were quantified as follows: NO by the Griess assay; prostaglandin (PG) E(2), interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha by ELISA; inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 by Western blotting; and NF-kappaB and CD14/TLR4 by Western blotting or flow cytometry. RESULTS: BSA- or FA-BSA-treated RAW264.7 cells without LPS stimulation did not show any significant changes in NO or the tested proteins/factors and thus did not have any pro-inflammatory responses. Pre-treatment with unsaturated FA-BSA complexes significantly decreased the production of LPS-induced NO, PGE(2), IL-6 and TNF alpha, the expression of iNOS, COX-2 and CD14, IkappaB degradation and NF-kappaB translocation. On the contrary, pre-treatment with saturated FA-BSA complexes enhanced these LPS-induced pro-inflammatory factors and the subsequent responses. CONCLUSIONS: We concluded that unsaturated FA-BSA complexes, but not saturated FA BSA complexes, exert an inhibitory effect on the LPS-induced pro-inflammatory response and that this effect may be partially mediated through suppression of the NF-kappaB signaling pathway. We suggest that an increase of unsaturated FA BSA complexes may enhance the host's defense against bacterial infection. PMID- 22094889 TI - Farnesoid x receptor agonists: what they are and how they might be used in treating liver disease. AB - The farnesoid X receptor (FXR) is a nuclear receptor expressed in the liver, small intestine, kidneys, and adrenals. In mouse liver, FXR is bound to thousands of genomic DNA binding sites. Conformational changes induced by bile acid binding to pre-bound FXR leads to increased expression of a variety of genes. These changes lead to decreased intracellular bile acid concentrations through multiple mechanisms including decreased bile acid synthesis from cholesterol, decreased hepatocellular uptake and increased secretion into bile. Activated FXR also modulates the expression of genes responsible for lipid and glucose metabolism. One of the other genes induced by activated FXR is a small heterodimeric partner (SHP), a protein that represses expression of specific genes. The effects of pharmacologically modulating FXR activation in humans is only beginning to be explored with the hopes of favorably altering lipid and glucose metabolism to address the vascular and metabolic complications of obesity and diabetes. PMID- 22094891 TI - A framework for characterizing eHealth literacy demands and barriers. AB - BACKGROUND: Consumer eHealth interventions are of a growing importance in the individual management of health and health behaviors. However, a range of access, resources, and skills barriers prevent health care consumers from fully engaging in and benefiting from the spectrum of eHealth interventions. Consumers may engage in a range of eHealth tasks, such as participating in health discussion forums and entering information into a personal health record. eHealth literacy names a set of skills and knowledge that are essential for productive interactions with technology-based health tools, such as proficiency in information retrieval strategies, and communicating health concepts effectively. OBJECTIVE: We propose a theoretical and methodological framework for characterizing complexity of eHealth tasks, which can be used to diagnose and describe literacy barriers and inform the development of solution strategies. METHODS: We adapted and integrated two existing theoretical models relevant to the analysis of eHealth literacy into a single framework to systematically categorize and describe task demands and user performance on tasks needed by health care consumers in the information age. The method derived from the framework is applied to (1) code task demands using a cognitive task analysis, and (2) code user performance on tasks. The framework and method are applied to the analysis of a Web-based consumer eHealth task with information-seeking and decision-making demands. We present the results from the in-depth analysis of the task performance of a single user as well as of 20 users on the same task to illustrate both the detailed analysis and the aggregate measures obtained and potential analyses that can be performed using this method. RESULTS: The analysis shows that the framework can be used to classify task demands as well as the barriers encountered in user performance of the tasks. Our approach can be used to (1) characterize the challenges confronted by participants in performing the tasks, (2) determine the extent to which application of the framework to the cognitive task analysis can predict and explain the problems encountered by participants, and (3) inform revisions to the framework to increase accuracy of predictions. CONCLUSIONS: The results of this illustrative application suggest that the framework is useful for characterizing task complexity and for diagnosing and explaining barriers encountered in task completion. The framework and analytic approach can be a potentially powerful generative research platform to inform development of rigorous eHealth examination and design instruments, such as to assess eHealth competence, to design and evaluate consumer eHealth tools, and to develop an eHealth curriculum. PMID- 22094892 TI - Synthesis, characterization and structural transformation of a discrete tetragonal metalloprism. AB - A novel M(2)L(4) tetragonal metalloprism, [(NO(3)(-))?{Cu(2)(MU Hdpma)(4)}(NO(3))(2)](NO(3))(5) (1), was prepared from the self-assembly reaction of Cu(NO(3))(2).3H(2)O and flexible clip-like organic ligand di(3 pyridylmethyl)amine (dpma) under acidic conditions. The cationic prismatic hollow structure of 1 hosts one nitrate anion via both metal-ligand dative bonds and electrostatic interactions. Metalloprism 1 can dissolve in water and its prismatic structure remains intact as supported by ESI-MS data. When metalloprism 1 was treated with sodium thiocyanate and sodium azide in aqueous solutions, two polymeric coordination architectures, [Cu(MU-Hdpma)(2)(NCS)(2)](NO(3))(2) (2) and [Cu(MU-dpma)(2)(MU-1,1-N(3))(MU-1,3-N(3))] (3), formed at room temperature, respectively. Polymer 2 has a two-dimensional sheet structure showing a simple rhombic 4(4)-sql topology in network connectivity, whereas polymer 3 gives a three-dimensional uninodal pcu net. The conformation of the flexible ditopic ligand is varied from a trans-trans-syn conformer in 1 to a trans-trans-anti conformer in 2 and to a trans-gauche-anti conformer in 3. The observations imply the occurrence of structural transformation from a discrete metalloprism into polymeric coordination architectures via a decoordination/rearrangement process. Magnetic studies of metalloprism 1 suggest that the two Cu(II) centers are weakly antiferromagnetically coupled. The spins communicate via the nitrate template while the Cu...O(nitrate) interactions are weak. For polymer 3, a ferromagnetically coupled system (J(2) = +17.6 cm(-1)) is operative between two Cu(II) centers bridged by end-on azidos and an antiferromagnetic coupling (J(1) = -7.7 cm(-1)) between two Cu(II) centers with end-to-end azidos. In contrast to relatively large coupling values of the reported examples, the weak ferromagnetic interaction results from insufficient spin delocalization between two Cu(II) centers. PMID- 22094890 TI - Genome-wide comparative analysis of pogo-like transposable elements in different Fusarium species. AB - The recent availability of genome sequences of four different Fusarium species offers the opportunity to perform extensive comparative analyses, in particular of repeated sequences. In a recent work, the overall content of such sequences in the genomes of three phylogenetically related Fusarium species, F. graminearum, F. verticillioides, and F. oxysporum f. sp. lycopersici has been estimated. In this study, we present an exhaustive characterization of pogo-like elements, named Fots, in four Fusarium genomes. Overall 10 Fot and two Fot-related miniature inverted-repeat transposable element families were identified, revealing a diversification of multiple lineages of pogo-like elements, some of which accompanied by a gain of introns. This analysis also showed that such elements are present in an unusual high proportion in the genomes of F. oxysporum f. sp. lycopersici and Nectria haematococca (anamorph F. solani f. sp. pisi) in contrast with most other fungal genomes in which retroelements are the most represented. Interestingly, our analysis showed that the most numerous Fot families all contain potentially active or mobilisable copies, thus conferring a mutagenic potential of these transposable elements and consequently a role in strain adaptation and genome evolution. This role is strongly reinforced when examining their genomic distribution which is clearly biased with a high proportion (more than 80%) located on strain- or species-specific regions enriched in genes involved in pathogenicity and/or adaptation. Finally, the different reproductive characteristics of the four Fusarium species allowed us to investigate the impact of the process of repeat-induced point mutations on the expansion and diversification of Fot elements. PMID- 22094893 TI - Contribution of the intestinal microbiota to human health: from birth to 100 years of age. AB - Our intestinal tract is colonized since birth by multiple microbial species that show a characteristic succession in time. Notably the establishment of the microbiota in early life is important as it appears to impact later health. While apparently stable in healthy adults, the intestinal microbiota is changing significantly during aging. After 100 years of symbiosis marked changes have been observed that may relate to an increased level of intestinal inflammation. There is considerable interest in the microbiota in health and disease as it may provide functional biomarkers, the possibility to differentiate subjects, and avenues for interventions. This chapter reviews the present state of the art on the research to investigate the contribution of the intestinal microbiota to human health. Specific attention will be given to the healthy microbiota and aberrations due to disturbances such as celiac disease, irritable bowel syndrome, inflammatory bowel disease, obesity and diabetes, and non-alcoholic fatty liver disease. PMID- 22094894 TI - Genetic prevalence and characteristics in children with recurrent pancreatitis. AB - AIMS: The causes of chronic (CP) and recurrent acute pancreatitis (RAP) in children include anatomic abnormalities and hereditary, metabolic, and autoimmune disorders, with a significant proportion of cases being labeled as idiopathic. Genetic pancreatitis (GP) is associated with mutations of cystic fibrosis transmembrane conductor regulator gene (CFTR), cationic trypsinogen (PRSS1) gene, and serine protease inhibitor Kazal type 1 (SPINK1). There literature is sparse regarding the clinical profile of GP in children. The aim of the present study was to estimate the prevalence and describe the clinical characteristics and outcome of genetic pancreatitis. METHODS: We reviewed the charts of children ages 18 years or younger with RAP or CP diagnosed from 2000 to 2009 at the Children's Hospital of Wisconsin, Milwaukee. Twenty-nine patients with RAP or CP were identified, of whom 23 (79%) were positive for mutations in >=1 of the above mentioned genes, and were included for review. RESULTS: The median age of symptom onset was 5 years (range 9 months-15 years) with diagnosis at 6.5 years (range 1 16 years). Twenty-one were white; 14 were girls. The most common presenting symptoms were abdominal pain and vomiting. Patients with RAP had 2 to 8 episodes of pancreatitis during 3.6-year average follow-up. Family history was positive in 5 of 29 of gene-tested patients. CFTR, SPINK1, or PRSS1 mutations were seen in 14 (48%), 8 (27%), and 7 (24%) patients, respectively. Two patients were homozygous for CFTR mutations, 6 heterozygote and 4 patients had 5 T variants. Two other patients had double heterozygous mutations in F508 del/2789 + 5G > A and F508 del/5T variant. Six patients with CP had a combination of CFTR and SPINK1 or PRSS1 mutations. Eleven of 29 (38%) patients met radiological criteria for CP. All of the heterozygote patients with a combination of CFTR and SPINK1 or PRSS1 mutations had CP. Eight patients developed a chronic pain syndrome and 2 developed exocrine pancreatic insufficiency during follow-up. CONCLUSIONS: We found a high prevalence of genetic mutations in patients without anatomic or metabolic abnormalities known to be associated with pancreatitis. Studies are needed to ascertain the genetic causes of RAP and CP and examine the relation between single CFTR mutations and single mutations in the PRSS1 and SPINK1 genes. PMID- 22094895 TI - Bone health in children with celiac disease assessed by dual x-ray absorptiometry: effect of gluten-free diet and predictive value of serum biochemical indices. AB - OBJECTIVES: In the present study, we aimed to assess bone status and the effect of gluten-free diet (GFD) in children with celiac disease (CD), and to evaluate the predictive value of standard serum biochemical indices in the diagnosis of bone mineral density (BMD) disturbances. METHODS: Forty-five children at the time of diagnosis of CD (group A, 77.8% girls) and 36 children receiving GFD for >2 years (group B, 75% girls) were included. Sixteen children in group A were reexamined 12 months after initiation of GFD. Serum measurements of biochemical bone health indices and BMD, assessed by dual x-ray absorptiometry, were obtained. RESULTS: Patients after 1 year of receiving GFD had higher BMD z scores compared with baseline (-1.45 +/- 0.28 vs -0.61 +/- 0.25, respectively, P = 0.004). BMD z scores were significantly lower than expected for the normal population, after 1 (P = 0.03) or at least 2 (P < 0.001) years of receiving GFD. In group B, BMD z score was positively correlated with 25-hydroxy vitamin D levels (P = 0.009). In the repeated measurements group, 25-hydroxy vitamin D differed between pre- and post-GFD (P = 0.018). No biochemical index was capable of predicting an abnormal BMD z score (receiver operating characteristic curve analysis, all of the areas under the curve <0.66). CONCLUSIONS: GFD has a beneficial effect on bone health. Two years receiving diet do not ensure normalization. Biochemical markers are not indicative of BMD disturbances. Dual x ray absorptiometry should be included in the standard management of children with CD. PMID- 22094896 TI - Nonbiopsy diagnosis of celiac disease: are we nearly there yet? PMID- 22094898 TI - Zinc and copper deficiency in the microvillus inclusion disease. PMID- 22094899 TI - Factors contributing to adherence to dietary treatment of eosinophilic gastrointestinal diseases. AB - The purpose of the present study was to identify barriers to dietary adherence found in the treatment of children with eosinophilic gastrointestinal diseases (EGIDs) and food allergy. A prospective study using a self-administered survey to parents of children with EGIDs at a national advocacy meeting was completed. Responses from 45 participants describing children ages 1 to 18 years (69% boys) identified that 63% were adherent to food restrictions. Physicians provided dietary instructions more often than dietitians. Nonadherence was associated with lack of school support (P < 0.027). Access to a dietitian may improve the care of children with EGIDs. PMID- 22094897 TI - Human milk adiponectin affects infant weight trajectory during the second year of life. AB - OBJECTIVE: Serum adiponectin (APN) is associated with lower childhood obesity, and APN concentration in human milk is associated with slower growth during active breast-feeding. We examined infant weight gain in the second year of life after exposure to high or low levels of mother's milk APN. METHODS: Breast feeding mother-infant pairs were recruited in Mexico City and studied for 2 years; 192 infants with at least 12 months' follow-up were analyzed. Monthly milk samples were assayed for APN; mothers were classified as producing high or low levels of milk APN. Infant and maternal serum APN were assessed during year 1. Infant anthropometry was measured monthly (year 1) or bimonthly (year 2), and World Health Organization z scores were calculated. Longitudinal adjusted models assessed weight-for-age and weight-for-length z score trajectories from 1 to 2 years. RESULTS: Maternal serum APN modestly correlated with milk APN (r=0.37, P<0.0001) and infant serum APN (r=0.29, P=0.01). Infants exposed to high milk APN experienced increasing weight-for-age and weight-for-length z scores between age 1 and 2 years in contrast to low milk APN exposure (P for group * time=0.02 and 0.054, respectively), adjusting for growth in the first 6 months and other covariates. In contrast, infant serum APN in year 1 was not associated with the rate of weight gain in year 2. CONCLUSIONS: High human milk APN exposure was associated with accelerated weight trajectory during the second year of life, suggesting its role in catch-up growth after slower weight gain during the first year of life. PMID- 22094900 TI - Health-related quality of life in pediatric patients with long-standing pancreatitis. AB - OBJECTIVES: There are limited data on health-related quality of life (HRQOL) in pediatric patients with long-standing pancreatitis (including acute relapsing and chronic pancreatitis) using age-appropriate measurement instruments. METHODS: We evaluated HRQOL in children with long-standing pancreatitis using the PedsQL 4.0 Generic Core Scales by patient self-report as well as parent proxy report. Additionally, patient self-reports and parent proxy reports were completed for the PedsQL Multidimensional Fatigue Scale. RESULTS: Across all of the dimensions, significantly impaired HRQOL and higher fatigue were noted for both pediatric patient self-report and parent proxy report in comparison with the matched healthy children samples. Higher fatigue was associated with lower HRQOL. There was moderate to good agreement between patient self-reports and parent proxy reports. CONCLUSIONS: Given the impaired HRQOL and fatigue documented in the present study, future studies are needed to determine whether specific factors can modify HRQOL and fatigue in this patient population. PMID- 22094901 TI - Utility of the new ESPGHAN criteria for the diagnosis of celiac disease in at risk groups. AB - OBJECTIVE: Demonstration of small-bowel mucosal damage has been the basis of celiac disease diagnosis, but the diagnostic approach is undergoing changes. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition recently stated that in a subgroup of children, high positive transglutaminase 2 antibody (TG2ab) values may be sufficient for the diagnosis. The utility of these new criteria was evaluated by applying the human red blood cell TG2 antibody test (RBC-TG2ab) to a large cohort of children and adults belonging to at-risk groups. METHODS: RBC-TG2ab and endomysial antibodies (EmA) were measured in 3031 family members or other relatives of patients with celiac disease. The RBC-TG2ab values were classified as weak (20-29 U), moderate (30-99 U), and strong (>=100 U) positive. Seropositive subjects were further tested by human recombinant TG2ab (Hr-TG2ab) and for the presence of celiac disease-associated human leukocyte antigen-DQ alleles. Gastroscopy was recommended for all with positive RBC-TG2ab, EmA, or Hr-TG2ab, or weak positive RBC-TG2ab and symptoms. RESULTS: Strong positive RBC-TG2ab has good correlation with EmA and Hr-TG2ab and positivity of DQ2/8, and the diagnosis was established in 94% of both children and adults. In contrast, moderately positive (>=30 U) RBC-TG2ab showed poor correlation with the other tests, and celiac disease was diagnosed in 69% of children and 86% of adults. Most participants with weak positive RBC-TG2ab were negative for EmA and Hr-TG2ab. CONCLUSIONS: In accordance with the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria, strong positive RBC-TG2ab showed good accuracy and excellent correlation with the other antibodies and celiac-type human leukocyte antigen. In contrast, low or moderately positive RBC TG2ab values were of unsatisfactory prognostic value for a subsequent diagnosis. PMID- 22094902 TI - Solitary rectal ulcer syndrome in children and adolescents. AB - OBJECTIVES: The aim of this study was to describe the presenting symptoms, endoscopic and histologic findings, and clinical courses of pediatric patients diagnosed with solitary rectal ulcer syndrome (SRUS). METHODS: We describe 15 cases of SRUS diagnosed at our institution during a 13-year period. Cases were identified by review of a pathology database and chart review and confirmed by review of biopsies. Data were collected by retrospective chart review. RESULTS: Presenting symptoms were consistent but nonspecific, most commonly including blood in stools, diarrhea alternating with constipation, and abdominal/perianal pain. Fourteen of 15 patients had normal hemoglobin/hematocrit, erythrocyte sedimentation rate, and albumin at diagnosis. Endoscopic findings, all limited to the distal rectum, ranged from erythema to ulceration and polypoid lesions. Histology revealed characteristic findings. Stool softeners and mesalamine suppositories improved symptoms, but relapse was common. CONCLUSIONS: SRUS in children presents with nonspecific symptoms and endoscopic findings. Clinical suspicion is required, and diagnosis requires histologic confirmation. Response to present treatments is variable. PMID- 22094903 TI - An overlooked entity in children with rectal bleeding: solitary rectal ulcer. PMID- 22094904 TI - Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells. AB - BACKGROUND: Treatment of early-stage osteonecrosis of the femoral head (ONFH) with autologous implantation of iliac crest bone marrow-derived mononuclear cells, which contain tens of thousands of bone marrow mesenchymal stem cells (BMMSCs), recently achieved a promising outcome. METHODS: One hundred patients with early-stage ONFH were recruited and randomly assigned to BMMSC treatment or core decompression (CD) treatment. Each BMMSC-treated hip received femoral head (FH) implantation of 2*10(6) autologous subtrochanteric bone marrow-derived and ex vivo expanded BMMSCs. The radiographic stage of ONFH according to the Association Research Circulation Osseous classification, Harris hip score (HHS), and the volume of the necrotic lesion or the low signal intensity zone (LowSIZ) in the FH were assessed before and 6, 12, 24, and 60 months after the initial operation. RESULTS: Sixty months after the operation, only 2 of the 53 BMMSC treated hips progressed and underwent vascularized bone grafting. In CD group, 7 hips lost follow-up, and 10 of the rest 44 hips progressed and underwent vascularized bone grafting (5 hips) or total hip replacement (5 hips). Compared with the CD group, BMMSC treatment significantly improved the HHS as well as decreased the volume of femoral head LowSIZ of the hips preoperatively classified at stage IC, IIB, and IIC (P<0.05, respectively; stage IIA, P=0.06, respectively). No complication was observed in both treatment groups. CONCLUSIONS: Ex vivo expansion of autologous BMMSCs can reliably provide a greater number of BMMSCs for FH implantation. This intervention is safe and effective in delaying or avoiding FH collapse, which may necessitate total hip replacement. PMID- 22094905 TI - Dysregulated expression of both the costimulatory CD28 and inhibitory CTLA-4 molecules in PB T cells of advanced cervical cancer patients suggests systemic immunosuppression related to disease progression. AB - Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients' T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. CONCLUSIONS: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression. PMID- 22094906 TI - Oncological outcome after free jejunal flap reconstruction for carcinoma of the hypopharynx. AB - It has been a common practice among the oncologist to reduce the dosage of adjuvant radiotherapy for patients after free jejunal flap reconstruction. The current aims to study potential risk of radiation to the visceral flap and the subsequent oncological outcome. Between 1996 and 2010, consecutive patients with carcinoma of the hypopharynx requiring laryngectomy, circumferential pharyngectomy and post-operative irradiation were recruited. Ninety-six patients were recruited. TNM tumor staging at presentation was: stage II (40.6%), stage III (34.4%) and stage IV (25.0%). Median follow-up period after surgery was 68 months. After tumor ablation, reconstruction was performed using free jejunal flap (60.4%), pectoralis major myocutaneous (PM) flap (31.3%) and free anterolateral thigh (ALT) flap (8.3%). All patients underwent adjuvant radiotherapy within 6.4 weeks after surgery. The mean total dose of radiation given to those receiving cutaneous and jejunal flap reconstruction was 62.2 Gy and 54.8 Gy, respectively. There was no secondary ischaemia or necrosis of the flaps after radiotherapy. The 5-year actuarial loco-regional tumor control for the cutaneous flap and jejunal flap group was: stage II (61 vs. 69%, p = 0.9), stage III (36 vs. 46%, p = 0.2) and stage IV (32 vs. 14%, p = 0.04), respectively. Reduction of radiation dosage in free jejunal group adversely affects the oncological control in stage IV hypopharyngeal carcinoma. In such circumstances, tubed cutaneous flaps are the preferred reconstructive option, so that full-dose radiotherapy can be given. PMID- 22094907 TI - Usefulness of urinary biomarkers in early detection of acute kidney injury after cardiac surgery in adults. AB - BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery. Urinary liver-type fatty acid-binding protein (L-FABP) reflects the presence of renal tubular injury. The aim of the present study was to evaluate the utility of urinary L-FABP compared with other urinary biomarkers for the early detection of postoperative AKI among adult patients undergoing cardiac surgery. METHODS AND RESULTS: Patients were divided into the AKI (n=48) and non AKI groups (n=37) according to whether they developed postoperative AKI within 48h after surgery. Changes in various biomarkers were evaluated. Urine and serum samples were obtained from each patient at the following time points: before the operation, immediately after the operation, and 3, 6, 18, 24, and 48h postoperatively. The urinary L-FABP level was significantly higher in the AKI group than in the non-AKI group at every time point, while other biomarkers did not show such a tendency. The biomarker with the largest area under the curve at every time point for predicting the onset of AKI was urinary L-FABP. On multiple logistic regression analysis, the urinary L-FABP level before operation and within the first 6h after cardiac surgery was significantly associated with the onset of AKI. CONCLUSIONS: Urinary L-FABP is a useful biomarker for early detection of AKI and is a good early predictor of the onset of AKI. PMID- 22094908 TI - Abnormal end-tidal PO(2) and PCO(2) at the anaerobic threshold correlate well with impaired exercise gas exchange in patients with left ventricular dysfunction. AB - BACKGROUND: The aim of the present study was to compare the end-tidal O(2) pressure (PETO(2)) to end-tidal CO(2) pressure (PETCO(2)) in cardiac patients during rest and during 2 states of exercise: at anaerobic threshold (AT) and at peak. The purpose was to see which metabolic state, PETO(2) or PETCO(2), best correlated with exercise limitation. METHODS AND RESULTS: Thirty-eight patients with left ventricular (LV) ejection fraction <40% underwent cardiopulmonary exercise testing (CPX). PETO(2) and PETCO(2) were measured during CPX, along with peak O(2) uptake (VO(2)), AT, slope of the increase in ventilation (VE) relative to the increase in CO(2) output (VCO(2)) (VE vs. VCO(2) slope), and the ratio of the increase in VO(2) to the increase in work rate (DeltaVO(2)/DeltaWR). Both PETO(2) and PETCO(2) measured at AT were best correlated with peakVO(2), AT, DeltaVO(2)/DeltaWR and VE vs. VCO(2) slope. PETO(2) at AT correlated with reduced peak VO(2) (r=-0.60), reduced AT (r=-0.52), reduced DeltaVO(2)/DeltaWR (r=-0.55) and increased VE vs. VCO(2) slope (r=0.74). PETCO(2) at AT correlated with reduced peak VO(2) (r=0.67), reduced AT (r=0.61), reduced DeltaVO(2)/DeltaWR (r=0.58) and increased VE vs. VCO(2) slope (r=-0.80). CONCLUSIONS: PETCO(2) and PETO(2) at AT correlated with peak VO(2), AT and DeltaVO(2)/DeltaWR, but best correlated with increased VE vs. VCO(2) slope. PETO(2) and PETCO(2) at AT can be used as a prime index of impaired cardiopulmonary function during exercise in patients with LV failure. PMID- 22094909 TI - Impact of body mass index on clinical outcome in patients hospitalized with congestive heart failure. AB - BACKGROUND: Obesity has recently been shown to have a favorable effect on the prognosis of patients with congestive heart failure (CHF), but only a few such studies are available in Japan. The purpose of the present study was to investigate whether the obesity paradox is still present after adjusting for CHF characteristics. METHODS AND RESULTS: A total of 219 patients hospitalized with CHF were reviewed, and the impact of body mass index (BMI) on prognosis was examined. Patients were divided into 4 groups according to BMI quartiles. The endpoint was defined as all-cause death or unplanned CHF hospitalization. According to univariate analysis, a higher BMI was associated with better outcomes. High-BMI patients were younger, likely to be male, and had a higher prevalence of hypertension and diabetes. The plasma B-type natriuretic peptide (BNP) levels and blood urea nitrogen (BUN) levels were lower, while the serum hemoglobin and sodium levels were higher in high-BMI patients. The prevalence of atrial fibrillation was lower in high-BMI patients. Predictors for all-cause death or CHF hospitalization based on univariate analysis were age, prior CHF hospitalization, estimated glomerular filtration rate, plasma BNP levels, BUN levels, and serum hemoglobin and sodium levels. According to multivariate analysis, a high BMI was still associated with better outcomes. CONCLUSIONS: High BMI was associated with better clinical outcomes in Japanese CHF patients. PMID- 22094910 TI - Clinical outcomes and hemodynamics of the 19-mm Perimount Magna bioprosthesis in an aortic position: comparison with the 19-mm Medtronic Mosaic Ultra Valve. AB - BACKGROUND: When aortic valve replacement is performed in patients with a small aortic annulus, prosthesis-patient mismatch (PPM) is of concern because it can affect postoperative clinical outcomes. Although larger bioprosthetic valves have been well studied, the hemodynamics of 19-mm bioprostheses have been reported in only a small number of patients. The effectiveness as well as the impact of PPM on outcomes are thus still unclear. METHODS AND RESULTS: Postoperative clinical and hemodynamic variables were compared in 67 patients with a 19-mm Carpentier Edwards Perimount Magna bioprosthesis and in 10 patients with a 19-mm Medtronic Mosaic Ultra valve. Mean follow-up time was 13 months. There was no in-hospital mortality. Echocardiography 6.5+/-4.0 months after surgery showed significant decreases in the mean left ventricular (LV)-aortic pressure gradient, and decreases in the mean LV mass index. Reduction in LV mass index did not differ between the valve groups, despite a higher pressure gradient in the Mosaic group. Although PPM was detected in 21 patients in the Magna group, it did not affect regression of the LV mass index during the follow-up period. CONCLUSIONS: Use of the 19-mm Magna bioprosthesis appears to provide satisfactory clinical results. LV-aortic pressure gradient was lower in the Magna group. The present data suggest that PPM is not related to reduction in the LV mass index. PMID- 22094912 TI - Predicting long-term mortality after first coronary revascularization: - the Kyoto model -. AB - BACKGROUND: We explored the determinants of mortality in order to develop and validate the Kyoto model, which predicts outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). METHODS AND RESULTS: A total of 9,393 patients who underwent their first coronary revascularization without concomitant valvular, left ventricular, or major vascular surgery were followed over a median follow-up of 3.5 years in the CREDO Kyoto Registry. We fitted separate Cox regression to mortality after PCI and CABG. The best-fitting model was internally validated by 10-fold cross validation. The Cox regression identified the following predictors: age, sex, body mass index, ejection fraction, atrial fibrillation, diabetes mellitus, hyperlipidemia, current smoker, stroke, peripheral vascular disease, chronic obstructive pulmonary disease, malignancy, kidney disease, anemia, liver cirrhosis, diseased vessel, left main disease, proximal left anterior descending artery disease, and total occlusion. This model simulated that the 3-year mortality for a hypothetical 70-year-old man with 2-vessel disease is 2.0% after PCI and 2.6% after CABG, or 4.2% and 5.1% if he has diabetes and chronic kidney disease. The Hosmer-Lemeshow test showed no significant deviations between the observed and predicted events. The C statistics were greater than 0.78. CONCLUSIONS: The Kyoto model can assist clinicians and patients in adherence to medication and lifestyle changes after revascularization and in individualized decision making. A web application is available at http://www.biostatistics.jp/prediction/kyoto-model. PMID- 22094911 TI - Effect of intensive lipid-lowering therapy with rosuvastatin on progression of carotid intima-media thickness in Japanese patients: Justification for Atherosclerosis Regression Treatment (JART) study. AB - BACKGROUND: A recent trial in Western countries has shown that rosuvastatin slows progression of carotid intima-media thickness (IMT) in patients with modest carotid IMT thickening and elevated levels of low-density lipoprotein cholesterol (LDL-C). We conducted a prospective, randomized, open-label, blinded-endpoint trial to determine whether rosuvastatin is more effective than pravastatin in slowing progression of carotid IMT in Japanese patients. METHODS AND RESULTS: Adult patients with hypercholesterolemia who had a maximum IMT >=1.1mm were randomly assigned to receive rosuvastatin or pravastatin. The primary endpoint was the percent change in the mean-IMT, which was measured by a single observer who was blinded to the treatment assignments. The trial was stopped on April 2011 according to the recommendation by the data and safety monitoring committee. A total of 348 patients (173 rosuvastatin; 175 pravastatin) were enrolled and 314 (159 rosuvastatin; 155 pravastatin) were included in the primary analysis. Mean (SD) percentage changes in the mean-IMT at 12 months were 1.91% (10.9) in the rosuvastatin group and 5.8% (12.0) in the pravastatin group, with a difference of 3.89% (11.5) between the groups (P=0.004). At 12 months, 85 patients (59.4%) in the rosuvastatin group achieved a LDL-C/high-density lipoprotein cholesterol ratio <=1.5 compared with 24 patients (16.4%) in the pravastatin group (P<0.0001). CONCLUSIONS: Rosuvastatin significantly slowed progression of carotid IMT at 12 months compared with pravastatin. PMID- 22094913 TI - Selective sinoatrial node optical mapping and the mechanism of sinus rate acceleration. AB - BACKGROUND: Studies using isolated sinoatrial node (SAN) cells indicate that rhythmic spontaneous sarcoplasmic reticulum calcium release (Ca clock) plays an important role in SAN automaticity. In the intact SAN, cross-contamination of optical signals from the SAN and the right atrium (RA) prevent the definitive testing of Ca clock hypothesis. The aim of this study was to use a novel approach to selectively mapping the intact SAN to examine the Ca clock mechanism. METHODS AND RESULTS: We simultaneously mapped intracellular Ca (Ca(i)) and membrane potential (V(m)) in 10 isolated, Langendorff-perfused normal canine RAs. The excitability of the RA was suppressed with high-potassium Tyrode's solution, allowing selective optical mapping of V(m) and Ca(i) of the SAN. Isoproterenol (ISO, 0.03 umol/L) decreased the cycle length of the sinus beats, and shifted the leading pacemaker site from the middle or inferior SAN to the superior SAN in all RAs. The Ca(i) upstroke preceded the V(m) in the leading pacemaker site by up to 18 +/- 2 ms. ISO-induced changes to SAN were inhibited by ryanodine (3 umol/L), but not ZD7288 (3 umol/L), a selective I(f) blocker. CONCLUSIONS: We conclude that, in the isolated canine RA, a high extracellular potassium concentration can suppress atrial excitability thus leading to SAN-RA conduction block, allowing selective optical mapping of the intact SAN. Acceleration of Ca cycling in the superior SAN underlies the mechanism of sinus tachycardia during sympathetic stimulation. PMID- 22094914 TI - Multifocal intraparenchymal Langerhans' cell histiocytosis concomitant with an arachnoid cyst in a child: case report and review of the literature. AB - Langerhans' cell histiocytosis is a disease usually found in children and characterized by idiopathic proliferation of histiocytes in the reticuloendothelial system. Intracranial Langerhans' cell histiocytosis presenting as multifocal intraparenchymal lesions is very rare. In this article, the authors report on a 4-year-old boy diagnosed with multifocal intraparenchymal Langerhans' cell histiocytosis concomitant with an arachnoid cyst. After a series of laboratory examinations, the right frontal mass was surgically excised. Histological examinations confirmed the diagnosis of intracranial Langerhans' cell histiocytosis. The patient's intracranial hypertension symptoms were alleviated, and the remaining foci were treated by Langerhans' cell histiocytosis directed standard chemotherapy. At the 8-month follow-up visit, no recurrence of the excised lesion was found, and no change in the size of other lesions was seen. Supratentorial intracerebral lesions with mass effect and enhancement have rarely been described; in this report, the histological features of and therapeutic options for such a case are discussed. PMID- 22094915 TI - Oligonephropathy of prematurity. AB - With improved health care, the number of premature babies who survive to adulthood is expected to increase. The objective of this review is to determine whether premature infants have an increased risk of chronic kidney disease (CKD). A literature review was performed by searching PubMed (U.S. National Library of Medicine) and the Cochrane Library, using the keywords "prematurity," "kidney," "nephrogenesis," "oligonephropathy," and "kidney impairment." Articles published in English since 1990 were reviewed. Increasing evidence suggests that prematurity causes oligonephropathy independently of, and coexisting with, intrauterine growth restriction. Animal studies show that nephrogenesis continues for up to 3 weeks in extrauterine life, but with up to 18% abnormal glomeruli. Nephrogenesis is further impaired in preterm infants who develop renal impairment in the early postnatal period, which is estimated to be 8 to 24%. Premature infants are at risk for CKD. A larger longitudinal study is needed that follows up premature infants to determine the exact incidence of CKD. Until then, renal assessment in premature infants should be incorporated into follow-up guidelines, in addition to the current assessment of growth and neurodevelopmental outcomes. The cost implications to a comprehensive program, impact of early identification, and strategies to improve outcomes in this population are needed. PMID- 22094916 TI - Midtrimester intra-amniotic sludge and the risk of spontaneous preterm birth. AB - We examined the association between midtrimester intra-amniotic sludge and spontaneous preterm birth (PTB) in asymptomatic women undergoing amniocentesis. We performed a prospective cohort study of women having an amniocentesis for fetal karyotyping between 14 and 24 weeks' gestation. Cervical length and the presence of amniotic sludge were assessed by transvaginal ultrasound. Amniotic fluid concentrations of matrix metalloproteinase-8, glucose and lactate were measured. Early (<32 weeks) and late (32 to 36 weeks) preterm premature rupture of membranes (PPROM) and spontaneous PTB constituted primary outcomes. Nonparametric analyses were conducted. Three hundred ten women, including 94 (30%) with free-floating echogenic particles and 16 (5%) with dense amniotic sludge, were recruited. Dense amniotic sludge was linked with early (13%) but not with late (0%) primary outcome ( P < 0.01). Two women with combined dense amniotic sludge and short cervix delivered 4 and 10 weeks later (at 20 and 25 weeks, respectively) and had a higher median amniotic lactate concentration than controls ( P < 0.05). A third woman with dense amniotic sludge at 15 weeks was diagnosed with a short cervix and an intra-amniotic infection at 22 weeks that was eradicated with intravenous antibiotics. Midtrimester dense amniotic sludge is associated with early PPROM and spontaneous PTB. PMID- 22094917 TI - Human milk versus formula feeding among preterm infants: short-term outcomes. AB - We evaluated short-term neonatal outcomes among preterm infants according to type of feeding administered (human milk or formula). Retrospective data were collected on 400 preterm infants at gestational age <=32 weeks. Groups were chosen and compared according to feeding type. The premature infants who were fed human milk had lower gestational age and birth weight than those who were formula fed. Lower rates of necrotizing enterocolitis (NEC) were detected in the group of infants fed human milk (p = 0.044). Lower rates of retinopathy of prematurity (ROP) were detected in a subgroup of breast-fed infants born at 24 to 28 weeks' gestational age, but the results did not reach statistical significance using univariate analysis (p = 0.06). Using multivariate analysis, however, ROP stage III among this subgroup was significantly lower (p = 0.022). No differences were recorded for other neonatal complications such as infections or for growth parameters. The advantage of human milk feeding, found mainly among preterm infants with respect to rates of NEC and ROP, supports efforts to encourage mothers to feed their infants human milk. PMID- 22094918 TI - Continuous glucose monitoring in diabetic women following antenatal corticosteroid therapy: a pilot study. AB - To compare the timing, duration, and severity of corticosteroid-associated hyperglycemia in pregnant women with and without diabetes mellitus (DM). An observational study was conducted of pregnant women with DM and controls who received corticosteroids. Median glucose levels were calculated over 4-hour intervals after the first dose of corticosteroid with a continuous glucose monitor. A glucose level increase of at least 15% above baseline was considered significant. Nine pregnant women participated in this study (six with DM and three without DM). Elevations of glucose levels occurred at hour 20, 44, and 68 in both groups and lasted for up to 4 hours. In those with DM, glucose levels increased 33 to 48%, whereas in those without DM, glucose levels rose 16 to 33%. Several, relatively short episodes of glucose elevation occur in response to corticosteroids, and are more pronounced in diabetic women. PMID- 22094919 TI - Preclosure fluid resuscitation influences outcome in gastroschisis. AB - Optimal preclosure fluid resuscitation in gastroschisis (GS) is unknown. The purpose of our study was to evaluate effects of preclosure intravenous fluid resuscitation on GS outcome. Cases were accrued from a national GS database. Risk variables analyzed included gestational age (GA), birth weight (BW), neonatal illness severity score, and bolus fluid administration within 6 hours of neonatal intensive care unit admission. Outcomes analyzed included closure success, days of ventilation/total parenteral nutrition (TPN), and bacteremic episodes. Linear and logistic regression analyses were performed. Four hundred seven live-born GS cases were identified (362 with complete resuscitative fluids data). Mean BW, GA, and Score for Neonatal Acute Physiology-II score were 2562 +/- 539 g, 36.17 +/- 1.95 weeks, and 9.97 +/- 12.65, respectively. One hundred sixty-two patients received no supplemental fluid, and 200 patients received a mean of 21.49 (0.81 to 134.81) mL/kg of intravenous fluid. Multivariate outcomes analyses demonstrated a significant, direct relationship between resuscitative volume and days of postclosure ventilation, TPN, length of hospital stay, and bacteremic episodes; specifically, every 17 mL/kg of fluid predicted one additional ventilation day (p = 0.002), TPN day (p = 0.01), and hospital day (p = 0.01) and 0.02 odds increase of an episode of bacteremia (p = 0.03). Judicious, preclosure fluid resuscitation is essential in early GS management. Excessive fluid is associated with several adverse survival outcomes. PMID- 22094920 TI - Single pass tangential flow filtration to debottleneck downstream processing for therapeutic antibody production. AB - As the therapeutic monoclonal antibody (mAb) market continues to grow, optimizing production processes is becoming more critical in improving efficiencies and reducing cost-of-goods in large-scale production. With the recent trends of increasing cell culture titers from upstream process improvements, downstream capacity has become the bottleneck in many existing manufacturing facilities. Single Pass Tangential Flow Filtration (SPTFF) is an emerging technology, which is potentially useful in debottlenecking downstream capacity, especially when the pool tank size is a limiting factor. It can be integrated as part of an existing purification process, after a column chromatography step or a filtration step, without introducing a new unit operation. In this study, SPTFF technology was systematically evaluated for reducing process intermediate volumes from 2* to 10* with multiple mAbs and the impact of SPTFF on product quality, and process yield was analyzed. Finally, the potential fit into the typical 3-column industry platform antibody purification process and its implementation in a commercial scale manufacturing facility were also evaluated. Our data indicate that using SPTFF to concentrate protein pools is a simple, flexible, and robust operation, which can be implemented at various scales to improve antibody purification process capacity. PMID- 22094922 TI - Effects of exercise training in heart transplant recipients: a meta-analysis. AB - OBJECTIVES: Muscle wasting and exercise intolerance are common in heart transplant recipients. Most studies on the effects of exercise training have used relatively small sample sizes and are heterogeneous in nature. The purpose of this meta-analysis was to systematically review the relevant studies and investigate the effects of exercise training on exercise capacity and muscle strength in heart transplant recipients. METHODS: A systematic search was adopted from electronic databases and relevant references, using medical subject heading key words related to heart transplantation and exercise. Only randomized controlled trials with exercise intervention versus usual care were included. The data were expressed as the weighted mean differences with 95% confidence intervals (CIs). RESULTS: Altogether 6 studies were included. Peak oxygen consumption (VO(2)) was reported in 4 trials (117 patients), and muscle strength was reported in 3 trials (67 patients). Peak VO(2) was significantly increased by 2.34 ml/kg/min (95% CI 0.63-4.05). One-repetition maxima of the chest press (23.28 kg, 95% CI 0.64-45.91) and leg press (28.84 kg, 95% CI 5.70-51.98) were significantly improved by exercise training. CONCLUSION: Exercise training is recommended for heart transplant recipients to improve peak VO(2) and muscle strength despite the small number of trials included in this meta-analysis. PMID- 22094921 TI - Prevalence of magnetic resonance imaging-defined atrophic and hypertrophic phenotypes of knee osteoarthritis in a population-based cohort. AB - OBJECTIVE: To describe the association of osteophytes with concomitant cartilage damage, assessed using semiquantitative magnetic resonance imaging (MRI), and to describe the prevalence of atrophic and hypertrophic phenotypes of tibiofemoral knee osteoarthritis (OA) in a population-based cohort. METHODS: Participants of the Framingham Knee Osteoarthritis Study were examined with a 1.5T MRI system using triplanar intermediate-weighted fat-suppressed sequences. Cartilage and osteophytes were assessed using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Overall prevalence of knees with severe cartilage damage and concomitant osteophyte status were described. Odds ratios for the likelihood of having severe cartilage damage according to osteophyte size were estimated using a logistic regression model. An additional analysis assessed knees according to phenotype in relation to radiographic OA status, with the atrophic phenotype being defined as knees with absent or only tiny osteophytes (WORMS grade <=2 on a 0-7 scale) in all 10 tibiofemoral subregions but exhibiting severe cartilage damage, and the hypertrophic phenotype being defined as knees with large osteophytes (WORMS grade >=5 on a 0-7 scale) but lacking substantial cartilage damage. RESULTS: In this study, 1,597 knees of 1,248 subjects were included. Of the 67 knees with large osteophytes, 54 (80.6%) exhibited severe cartilage damage. The risk of severe cartilage damage increased markedly with increasing osteophyte size. Twenty-one knees (1.3%) showed an atrophic phenotype. Only 3 knees (0.2%) exhibited a hypertrophic phenotype. CONCLUSION: The majority of knees with severe tibiofemoral cartilage damage exhibited moderate to large osteophytes. The larger the osteophyte, the more likely was the presence of severe cartilage damage. A minority of knees exhibited the atrophic phenotype, which also included knees without radiographic OA. The hypertrophic phenotype was extremely rare. PMID- 22094923 TI - Diagnostic accuracy of noninvasive detection of fetal trisomy 21 in maternal blood: a systematic review. AB - BACKGROUND: Both pregnant women and providers of obstetric care are aware of the rapid advances in noninvasive prenatal diagnosis (NIPD) of fetal trisomies, and appear to look forward to its clinical introduction. OBJECTIVES: To review and critically assess the published literature on diagnostic accuracy of NIPD using cell-free fetal DNA or RNA in maternal blood to detect fetal trisomy 21. METHOD: An electronic search was performed in MEDLINE, EMBASE and the Cochrane library (1997 to April 2011). Of a total of 201 citations, 9 studies were eligible for full-text analysis by 2 independent reviewers, using the QUADAS tool. RESULTS: Two of the 9 analyzed studies complied with the criteria of the QUADAS tool. Combining the selected 2 studies, with a total of 681 pregnancies included, overall sensitivity was 125/125 (100%, 95% CI 97.5-100%) and specificity 552/556 (99.3%, 95% CI 98.7-99.3%). CONCLUSIONS: NIPD of fetal trisomy 21, using fetal nucleic acids in maternal plasma, appears to have a high diagnostic accuracy. Large-scale prospective studies are awaited before implementation in clinical practice. PMID- 22094925 TI - Exploring the microbial metalloproteome using MIRAGE. AB - The microbial metalloproteome has been largely unexplored. Using the metalloproteomics approach MIRAGE (Metal Isotope native RadioAutography in Gel Electrophoresis) we have been able to explore the soluble Fe and Zn metalloproteome of Escherichia coli. The protein identification by MS/MS typically resulted in several overlapping proteins for each metal containing spot. Using the E. coli genome annotation the proteins relevant to the iron and zinc proteome were selected. Superoxide dismutase (SodB) was found to be the major iron protein after cultivation with a normal iron concentration of 6 MUM. Upon an elevated iron concentration of 40 MUM, ferritin (FtnA) became dominant. Under both conditions 90% of the iron was associated with just three different proteins: superoxide dismutase (SodB), ferritin (FtnA) and bacterioferritin (Bfr). The uncharacterized proteins YgfK and XdhD were found to be significant iron containing proteins under elevated iron conditions. The zinc proteome of E. coli experiencing zinc stress was dominated by ZraP, a putative zinc storage protein. PMID- 22094924 TI - Research advances in gene therapy approaches for the treatment of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease of motor neurons that causes progressive muscle weakness, paralysis, and premature death. No effective therapy is available. Research in the motor neuron field continues to grow, and recent breakthroughs have demonstrated the possibility of completely achieving rescue in animal models of spinal muscular atrophy, a genetic motor neuron disease. With adeno-associated virus (AAV) vectors, gene transfer can be achieved with systemic non-invasive injection and minimal toxicity. In the context of this success, we review gene therapy approaches for ALS, considering what has been done and the possible future directions for effective application of the latest generation of vectors for clinical translation. We focus on recent developments in the areas of RNA/antisense mediated silencing of specific ALS causative genes like superoxide dismutase-1 and other molecular pathogenetic targets, as well as the administration of neuroprotective factors with viral vectors. We argue that gene therapy offers new opportunities to open the path for clinical progress in treating ALS. PMID- 22094926 TI - Understanding UV-driven metabolism in the hypersaline ciliate Fabrea salina. AB - By using NMR spectroscopy, a non-invasive investigation technique, we performed in vivo experiments aimed at uncovering the metabolic pathways involved in the early response of Fabrea salina cells to ultraviolet (UV) radiation. This hypersaline ciliate was chosen as a model organism because of its well-known high resistance to UV radiation. Identical cell samples were exposed to visible radiation only (control samples, CS) and to UV-B + UV-A + visible radiation (treated samples, TS), and NMR spectra of in vivo cells were collected at different exposure times. Resonances were identified through one- and two dimensional experiments. To compare experiments performed at variable irradiation times on different culture batches, metabolite signals affected by the UV exposure were normalized to corresponding intensity at tau = 0, the zero exposure time. The most affected metabolites are all osmoprotectants, namely, choline, glycine-betaine, betaines, ectoine, proline, alpha-trehalose and sucrose. The time course of these signals presents qualitative differences between CS and TS, and most of these osmoprotectants tend to accumulate significantly in TS in a UV dose-dependent manner. A picture of the immediate stress response of F. salina against UV radiation in terms of osmoprotection, water retention and salting-out prevention is described. PMID- 22094927 TI - Population-level response shift: novel implications for research. AB - OBJECTIVES: Response shift is a change in perceived HRQL that occurs as a result of recalibration, reprioritization, or reconceptualization of an individual respondent's internal standards, values, or conceptualization of HRQL. In this commentary, we suggest that response shift may also occur at the population level, triggered by causes that affect the distribution of individual-level risk. METHODS: We illustrated the nature and consequences of potential population-level response shift with two examples: the September 11 terror attacks, and the recent denormalization of smoking. RESULTS: Response shift may occur at the population level, when a large proportion of the population experiences the shift simultaneously, as a unit, and when the cause of the response shift is a socially significant event or trend. Such catalysts are of a qualitatively different nature than the causes leading to health status changes among individuals, and speak to the determinants affecting the underlying distribution of risk in the population. CONCLUSIONS: We do not know if population-level causes have actually resulted in response shifts. Nonetheless, response shifts at the population-level may be worthwhile to investigate further, both to assess the validity of research evidence based on the measurement of HRQL in large populations, and as a desirable intermediate outcome in evaluations of population health programs. PMID- 22094928 TI - Association of the 463G-A myeloperoxidase gene polymorphism with gastric cancer risk. AB - BACKGROUND/AIMS: To explore the association between polymorphism of myeloperoxidase (MPO) gene and the susceptibility to gastric cancer. METHODOLOGY: A case control study of 117 gastric cancer patients and 105 controls was conducted to investigate the polymorphism of MPO gene 463G-A using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The association between polymorphism and the risk of gastric cancer was examined by a multivariate analysis. Stratification analysis by age, gender, smoking status, H. pylori (Hp) infection and family history of gastric cancer was performed. RESULTS: In gastric cancer group the frequencies of the cases caring genotype G/G, G/A, A/A were 70.94%, 25.64% and 3.42%, respectively. In healthy control group, the frequency of genotype G/G, G/A, A/A was 51.43%, 37.14% and 11.43%, respectively. The frequency of genotype G/A and A/A in cancer group was found significantly higher than that in healthy control group (p<0.05). Compared with the MPO-463 G/G genotype, individuals with GA/AA genotype had a significantly decreased risk of gastric cancer (OR=0.50, 95%CI=0.28-0.90). In the stratification analysis, patients younger than 60 years old, male, Hp-IgG negative and with no family history of gastric cancer with genotype GA/AA had lower risk than those with genotype G/G. CONCLUSIONS: MPO gene polymorphism is associated with susceptibility of gastric cancer. It is conceivable that carriers of the A allele may be at reduced risk of gastric cancer. PMID- 22094929 TI - Urinary complications in rectal cancer patients are related to the dissection tool. AB - BACKGROUND/AIMS: To assess the incidence and risk of urinary complications after anterior rectal cancer resection with regard to the surgical device used for total mesorectal excision (TME). METHODOLOGY: During the years 2004-2009 we operated 374 rectal cancer patients with TME and the intent of autonomic nerves sparing intent. Seventeen patients underwent mesorectal dissection with ultrasound scalpel (US). They were compared to the control series of 35 cases selected from the patients for whom electrocautery was used. Selection was done in the manner to eliminate any other significant differences between groups. RESULTS: Intraoperative complications, postoperative mortality, anastomotic leakage and infectious complications did not occur. Urinary bladder disturbances developed in US group in 1 patient (6%) while in 12 patients (34%) in EC group (p<0.05). In US group the character of complication was transient stress incontinence with symptoms being significantly reduced during six postoperative months. In EC group two patients had dysuria, two nycturia, one had both. Stress incontinence occurred in six patients, complete incontinence requiring catheterization in one. CONCLUSIONS: When compared to EC, TME with US is related to lower risk of urinary complications and facilitates autonomic nerve preservation due to minimized thermal lateral tissue damage. PMID- 22094930 TI - Partial pancreatic resection for pancreatic malignancy is associated with sustained pancreatic exocrine failure and reduced quality of life: a prospective study. AB - OBJECTIVES: Pancreatic resection for cancer may produce pancreatic exocrine insufficiency (PEI), which is poorly understood. This study examined the coefficient of fat absorption (CFA), symptoms, quality of life (QoL) and the accuracy of faecal elastase-1 (FE-1) measurement to predict PEI. METHODS: Forty patients were analysed following resection for pancreatic malignancy. The primary endpoint was PEI diagnosis defined by CFA <93%; secondary endpoints were PEI diagnosis using FE-1 <200 MUg/g, body mass index (BMI), and symptom and QoL analysis. Interventions were 3-day stool collection, EORTC QLQ-C30 (version 1) questionnaire and patient's diary, at 6 weeks and 3, 6 and 12 months after surgery. RESULTS: CFA <93% was present in 67% of patients at 6 weeks and in 55% at 12 months. PEI using FE-1 was present in 77 and 83% of patients, respectively. No significant changes between time-points were observed. Sensitivity, specificity, PPV, NPV and accuracy for FE-1 in detecting CFA <93% were 91, 35, 70, 71 and 70%, respectively. CFA and FE-1 levels were uncorrelated. Overall, QoL increased at 6 (p = 0.0212) and 12 (p < 0.0001) months after surgery, mainly driven by physical, role and social functioning, and by appetite. Importantly, however, BMI and symptoms were unaffected by PEI, which suggests a subclinical presentation; such patients had attributes indicating poorer QoL (notably insomnia, p = 0.0012). CONCLUSIONS: PEI was common and sustained following resection and not associated with significant symptoms. These patients had a tendency toward poorer QoL. FE-1 is a poor surrogate for diagnosing impaired fat absorption. Postoperative pancreatic enzyme replacement should be considered more routinely. and IAP. PMID- 22094931 TI - Prediction of persistent gestational trophobalstic neoplasia: the role of hCG level and ratio in 2 weeks after evacuation of complete mole. AB - OBJECTIVE: The aim of this study was to determine whether or not the serum human chorionic gonadotropin (hCG) level and ratio during 2 weeks after evacuation is predictive of persistent gestational trophoblastic neoplasia (GTN) in patients with complete molar pregnancies. METHODS: Between January 2000 and June 2010, a total of 467 patients with complete molar pregnancies were diagnosed. Seventeen patients, who had prophylactic chemotherapy and in whom insufficient data were available, were excluded. A receiver operating characteristic curve was used to determine the most useful predictive factor for persistent GTN and multivariate logistic regression was used for analyses. RESULTS: Persistent GTN was diagnosed in 109 of the 450 patients (24.2%) on the basis of the 2000 FIGO criteria. The optimal cut-off point for hCG 1 and 2 weeks after evacuation was 6400 mIU/mL (sensitivity, 54.1%; specificity, 65.1%) and 2400 mIU/mL (sensitivity, 64.2%; specificity, 78.3%), respectively. The optimal cut-off point for the ratio of pre evacuation hCG to hCG 2 weeks after evacuation was 30 (sensitivity, 63.3%; specificity, 86.5%). Based on multivariate analysis, this ratio<30 was an independent predictive factor for persistent GTN (odds ratio=6.885; 95% confidence interval, 4.006-11.832; P<0.001). CONCLUSIONS: The decline ratio in hCG level 2 weeks after evacuation in patients with complete molar pregnancies is the most reliable predictor of persistent GTN. Our analysis may allow clinicians to stratify risk in patients with complete molar pregnancies and to provide more accurate counseling based on the hCG levels obtained 2 weeks after evacuation. PMID- 22094932 TI - Cognitive function and quality of life in ovarian cancer. AB - OBJECTIVES: As advances in treatment have prolonged survival for many patients with ovarian cancer, there has been growing interest in assessing the adverse effects of disease and treatment. The aim of this study was to review the literature on cognitive function and quality of life (QOL) in this population. METHODS: A review of published studies including formal assessment of neurocognitive functions and self-reported domains of quality of life, with an emphasis on cognitive function, was performed. RESULTS: The small number of studies including formal evaluations of neurocognitive function suggests that many ovarian cancer patients experience cognitive difficulties associated with their disease and treatment. Several studies described declines in self-reported cognitive function that may impact QOL, but the results were not consistent across studies. CONCLUSIONS: Adequately powered longitudinal studies including formal neurocognitive and QOL assessments are needed to advance our understanding of the incidence of cognitive dysfunction and its impact on functional ability and QOL in ovarian cancer patients. These research efforts may ultimately contribute to treatment decision-making through the identification of vulnerable patients, and to the development of appropriate intervention strategies to improve cognitive function and QOL. PMID- 22094933 TI - Whither the PET scan? The role of PET imaging in the staging and treatment of breast cancer. AB - Metabolic imaging may contribute to a better knowledge of the biology of breast cancer and to new drugs development. Positron emission tomography (PET) with the radiolabeled glucose analogue 2- [18F]-fluorodeoxyglucose (18F-FDG) allows quantitative assessment of glucose utilization in tumor tissue. This technique utilizes a class of radioisotopes that decay by emitting a positron. The positron travels a short distance (1 mm) before interacting with an electron in what is called an annihilation reaction. This results in the creation of two high-energy photons that are emitted in opposite directions. The PET scanner detects such annihilation radiations and produces a three-dimensional picture of the distribution of the radiolabeled tracer. 18F-FDG PET has currently a limited role in breast cancer, due to its low sensitivity that makes it not recommended in most of the cases, especially in early disease. Potentially, the most useful application of PET/CT is monitoring the changes in 18F-FDG uptake during chemotherapy in order to detect an early response to treatment. In fact, while morphological changes due to effective chemotherapy are not detectable until late in the course of treatment, metabolic changes generally occur earlier. In this paper, we summarize the current and future applications of PET in the management of breast cancer. PMID- 22094934 TI - Phase II trial of preoperative paclitaxel, gemcitabine, and trastuzumab combination therapy in HER2 positive stage II/III breast cancer: the Korean Cancer Study Group BR 07-01. AB - An addition of trastuzumab preoperatively to chemotherapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer improved relapse-free survival (RFS). This study was designed to evaluate the efficacy and safety of preoperative paclitaxel, gemcitabine, and trastuzumab (PGH) combination for HER2 positive breast caner. Pathologically, proven node positive stage II/III breast cancer patients with adequate organ function and no history of anti-cancer therapy were eligible. Patients received weekly trastuzumab with paclitaxel 80 mg/m(2) and gemcitabine 1,200 mg/m(2) on days 1 and 8, every 3 weeks for 6 cycles. Postoperatively, patients completed trastuzumab for 1 year and hormone therapy for 5 years if indicated. All patients received postoperative radiation therapy. Of 53 enrolled patients with a median tumor of 5.3 (range, 2.0 to >12) cm; 43.4%, T3/T4; 75.4%, N2/N3; and 45.3%, positive hormone receptors. The pathologic complete response (pCR) rate was 58.5% in both tumor and lymph nodes. Grade 3/4 adverse events were neutropenia (32%), febrile neutropenia (0.6%), and transient elevation of AST/ALT (1.6%) during a total of 318 cycles. All patients maintained normal cardiac function. With a median follow-up of 40 months, 3-year RFS rate was 84% with 91.7% distant metastasis-free survival rates. Remarkable pCR rate was obtained with non-anthracycline-based PGH therapy for HER2-positive stage II/III breast cancer. Adverse events were mild with few incidences of febrile neutropenia. PMID- 22094935 TI - A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. AB - Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERalpha, ERbeta1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phenotype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95% CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95% CI = 0.46 1.26) and both 5 (P = 0.04, HR = 0.37, 95% CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95% CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ERbeta1/2 clusters. A striking feature was the occurrence of ERalpha on distinct clusters between genders. In female breast cancer, ERalpha clustered with PR and its isoforms; in male breast cancer, ERalpha clustered with ERbeta isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study. PMID- 22094936 TI - High miR-26a and low CDC2 levels associate with decreased EZH2 expression and with favorable outcome on tamoxifen in metastatic breast cancer. AB - For patients with metastatic breast cancer, we previously described that increased EZH2 expression levels were associated with an adverse outcome to tamoxifen therapy. Main objective of the present study is to investigate miR-26a and miR-101 levels, which both target EZH2, for their association with molecular pathways and with efficacy of tamoxifen as first-line monotherapy for metastatic breast cancer. Expression levels were measured using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) in primary breast cancer specimens of 235 estrogen receptor-alpha (ER)-positive patients. Pathway analysis was performed on microarray data available for 65 of these tumors. Logistic regression and Cox uni and multivariate analysis were performed to relate expression levels with clinical benefit and time to progression (TTP). Increasing levels of miR-26a were significantly (P < 0.005) associated with both clinical benefit and prolonged TTP, whereas miR-101 was not. Cell cycle regulation and CCNE1 and CDC2 were the only significant overlapping pathway and genes differentially expressed between tumors with high and low levels of miR-26a and EZH2, respectively. In addition, increasing mRNA levels of CCNE1 (P < 0.05) and CDC2 (P < 0.001) were related to poor outcome. Multivariate analysis revealed miR-26a and CDC2 as an optimal set of markers associated with outcome on tamoxifen therapy, independently of traditional predictive factors. To summarize, only miR-26a levels are related with treatment outcome. Cell cycle regulation is the only overlapping pathway linked to miR-26a and EZH2 levels. Low mRNA levels of EZH2, CCNE1, and CDC2, and high levels of miR-26a are associated with favorable outcome on tamoxifen. PMID- 22094937 TI - Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial. AB - Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin((r))) and paclitaxel (Taxol((r))) alone (ET) or in combination with capecitabine (Xeloda((r)), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (chi(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome. PMID- 22094938 TI - Serum enterolactone levels and mortality outcome in women with early breast cancer: a retrospective cohort study. AB - We previously demonstrated that high serum enterolactone levels are associated with a reduced incidence of breast cancer in healthy women. The present study was aimed at investigating whether a similar association might be found between serum enterolactone levels and the mortality of women with early breast cancer. The levels of enterolactone in cryopreserved serum aliquots obtained from 300 patients, operated on for breast cancer, were measured using a time-resolved fluoro-immunoassay. Levels were analyzed in respect to the risk of mortality following surgery. Cox proportional hazard regression models were used to check for prognostic features, to estimate hazard ratios for group comparisons and to test for the interaction on mortality hazards between the variables and enterolactone concentrations. The Fine and Gray competing risk proportional hazard regression model was used to predict the probabilities of breast cancer related and breast cancer-unrelated mortalities. At a median follow-up time of 23 years (range 0.6-26.1), 180 patients died, 112 of whom died due to breast cancer related events. An association between a decreased mortality risk and enterolactone levels >= 10 nmol/l was found in respect to both all-cause and breast cancer-specific mortality. The difference in mortality hazards was statistically significant, but it appeared to decrease and to lose significance after the first 10 years, though competing risk analysis showed that breast cancer-related mortality risk remained constantly lower in those patients with higher enterolactone levels. Our findings are consistent with those of most recent literature and provide further evidence that mammalian lignans might play an important role in reducing all-cause and cancer-specific mortality of the patients operated on for breast cancer. PMID- 22094941 TI - Molecular evolution: dealing with nonsense. PMID- 22094943 TI - Microbiomes: getting down to mechanism. PMID- 22094948 TI - Evolution of microRNA diversity and regulation in animals. AB - In the past decade, microRNAs (miRNAs) have been uncovered as key regulators of gene expression at the post-transcriptional level. The ancient origin of miRNAs, their dramatic expansion in bilaterian animals and their function in providing robustness to transcriptional programmes suggest that miRNAs are instrumental in the evolution of organismal complexity. Advances in understanding miRNA biology, combined with the increasing availability of diverse sequenced genomes, have begun to reveal the molecular mechanisms that underlie the evolution of miRNAs and their targets. Insights are also emerging into how the evolution of miRNA containing regulatory networks has contributed to organismal complexity. PMID- 22094950 TI - Error prevention and mitigation as forces in the evolution of genes and genomes. AB - Why are short introns rarely a multiple of three nucleotides long? Why do essential genes cluster? Why are genes in operons often lined up in the order in which they are needed in the encoded pathway? In this Opinion article, we argue that these and many other - ostensibly disparate - observations are all pieces of an emerging picture in which multiple aspects of gene anatomy and genome architecture have evolved in response to error-prone gene expression. PMID- 22094952 TI - Gene-by-environment experiments: a new approach to finding the missing heritability. PMID- 22094949 TI - Non-coding RNAs in human disease. AB - The relevance of the non-coding genome to human disease has mainly been studied in the context of the widespread disruption of microRNA (miRNA) expression and function that is seen in human cancer. However, we are only beginning to understand the nature and extent of the involvement of non-coding RNAs (ncRNAs) in disease. Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis. Along with microRNAs, dysregulation of these ncRNAs is being found to have relevance not only to tumorigenesis, but also to neurological, cardiovascular, developmental and other diseases. There is great interest in therapeutic strategies to counteract these perturbations of ncRNAs. PMID- 22094954 TI - Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: 1-year results of a randomized clinical trial. AB - BACKGROUND: Cytomegalovirus (CMV) prevention can be achieved by prophylaxis or preemptive therapy. We performed a prospective randomized trial to determine whether renal transplant recipients with a positive CMV serostatus (R+) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection, compared with primary valganciclovir prophylaxis. METHODS: Prophylaxis was 2 * 450 mg oral valganciclovir/day for 100 days; preemptive patients were monitored by CMV-polymerase chain reaction (PCR), and after a positive PCR test received 2 * 900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis. Valganciclovir dosage was adjusted according to renal function. Patients are followed up for 5 years and initial 12 month data are presented. Two hundred and ninety-six recipients were analyzed (168 donor/recipient seropositive [D+/R+], 128 donor seronegative/recipient seropositive [D-/R+]; 146 receiving prophylaxis and 150 preemptive therapy). RESULTS: Overall, CMV infection (asymptomatic CMV viral load >= 400 CMV DNA copies/mL proven by CMV-PCR) was significantly higher in recipients under preemptive therapy (38.7% vs. 11.0%, P<0.0001), with the highest incidence in D+/R+ preemptive patients (53.8% vs. 15.6%, P<0.0001). D+/R+ recipients with preemptive therapy also had the highest rate of CMV disease (CMV syndrome and tissue-invasive disease that was clinically diagnosed and biopsy proven) (19.2% vs. 4.4%, P=0.003). Renal function assessed by creatinine clearance was similar for both groups. Graft loss occurred in 7 vs. 4 patients on preemptive versus prophylactic therapy (P>0.05). Tolerability was similar for both treatment groups. CONCLUSIONS: Oral valganciclovir prophylaxis significantly reduces CMV infection and disease, particularly for D+/R+ patients. Hence, our study supports routine prophylaxis for all D+/R+ recipients. PMID- 22094955 TI - Splenectomy does not offer immunological benefits in ABO-incompatible liver transplantation with a preoperative rituximab. AB - BACKGROUND: Preformed anti-ABO antibodies are primarily responsible for antibody mediated rejection (AMR) after ABO-incompatible (ABO-I) liver transplantation (LT) resulting in lethal hepatic necrosis and biliary complications. Splenectomy, an integral part of protocol for ABO-I LT, decreases anti-ABO antibodies. With the preoperative rituximab prophylaxis, role of the splenectomy for ABO-I LT is now under debate. We investigated the necessity of splenectomy by retrospective analyses of the short-term anti-ABO antibody response and long-term outcomes of ABO-I LT. METHODS: Thirty-seven ABO-I LTs performed from May 2006 through July 2009, at Kyoto University Hospital, Kyoto, Japan, were retrospectively analyzed. Twenty-seven patients who underwent splenectomy (splenectomy group) received 329.6 +/- 35.8 mg rituximab 17.7 +/- 11.9 days before living donor LT. Ten patients without splenectomy (nonsplenectomy group) received 320.0 +/- 10.3 mg rituximab 26.6 +/- 21.3 days before transplantation. All patients received a posttransplant hepatic artery infusion with prostaglandin E1 and methylprednisolone. Perioperative anti-ABO immunoglobulin M and immunoglobulin G antibody titers, rejections, biliary complications, infections, and survival results were compared. RESULTS: Preoperative rituximab with plasma exchange effectively reduced anti-ABO antibodies in both patient groups at the time of LT. There was no statistically significant difference observed in anti-ABO immunoglobulin M and immunoglobulin G antibody titers between the "splenectomy" and "nonsplenectomy" groups during the initial 8 weeks. The clinical outcomes, including AMR, biliary complications, infections, and survival, were similar in both the groups. CONCLUSIONS: Preoperative rituximab effectively decreased the anti-ABO antibodies sufficiently to prevent the AMR irrespective of splenectomy. Splenectomy does not offer any immunological benefit in ABO-I LT with preoperative rituximab. PMID- 22094953 TI - Associations of ABCB1 3435C>T and IL-10-1082G>A polymorphisms with long-term sirolimus dose requirements in renal transplant patients. AB - BACKGROUNDS: Sirolimus (SRL) absorption and metabolism are affected by p glycoprotein-mediated transport and CYP3A enzyme activity, which are further under the influences of cytokine concentrations. This retrospective study determined the associations of adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) 1236C>T, 2677 G>T/A, and 3435C>T, cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) -392A>G, cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5) 6986A>G and 14690G>A, interleukin (IL)-10 -1082G>A, and tumor necrosis factor (TNF) -308G>A polymorphisms with SRL dose-adjusted, weight normalized trough concentrations (C/D) at 7 days, and at 1, 3, 6, and 12 months after initiation of SRL. METHODS: Genotypes for 86 renal transplant patients who received SRL-based maintenance immunosuppressive therapy were determined using polymerase chain reaction followed by chip-based mass spectrometry. The changes of log-transformed C/D over the days posttransplantation were analyzed using a linear mixed-effects model, with adjustments for body mass index and weight normalized doses of tacrolimus, prednisone, clotrimazole, and statins. RESULTS: ABCB1 3435C>T and IL-10 -1082G>A were significantly associated with log C/D (P=0.0016 and 0.0394, respectively). Mean SRL C/D was 48% higher in patients with ABCB1 3435CT/TT genotype than those with 3435CC genotype, and was 24% higher in IL-10 -1082GG compared with -1082AG/AA. CONCLUSIONS: ABCB1 3435C>T and IL-10 1082G>A were significantly associated with long-term SRL dose requirements. Genetics can play a significant role in SRL dosing and may be useful in therapeutic monitoring of SRL in renal transplantation. Future replication studies are needed to confirm these associations. PMID- 22094956 TI - How to increase organ donation: does opting out have a role? AB - Every country needs to increase the number of deceased organ donors and the potential impact of a change to opting-out legislation remains unproven, despite the apparent association between opting out and higher donor rates. However, the Spanish model--so successful in Spain and many other countries--is not based on a requirement for opting out, and, in the UK, deceased organ donation has increased by 25% in 3 years through implementation of a series of recommendations that have transformed the infrastructure of donation. A major review of opting out concluded that it is not appropriate for the UK at this time. PMID- 22094957 TI - Early subclinical rejection as a risk factor for late chronic humoral rejection. AB - BACKGROUND: Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause. MATERIALS AND METHODS: Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause. RESULTS: Of the 517 renal transplants with a protocol biopsy, 109 had a subsequent biopsy for cause which showed the following histological diagnoses: chronic humoral rejection (CHR) (n=44), IF/TA (n=42), recurrence of the primary disease (n=11), de novo glomerulonephritis (n=7), T-cell-mediated rejection (n=4), and polyoma virus nephropathy (n=1). The proportion of retransplants (15.9% vs. 2.3%, P=0.058) and the prevalence of subclinical rejection were higher in patients with CHR than in patients with IF/TA (52.3% vs. 28.6%, P=0.0253). Demographic donor and recipient characteristics and clinical data at the time of protocol biopsy were not different between groups. Logistic regression analysis showed that subclinical rejection (relative risk, 2.52; 95% confidence interval, 1.1-6.3; P=0.047) but not retransplantation (relative risk, 6.7; 95% confidence interval, 0.8-58.8; P=0.085) was associated with CHR. CONCLUSION: Subclinical rejection in early protocol biopsies is associated with late appearance of CHR. PMID- 22094958 TI - What is the significance of subclinical inflammation in human renal allografts? It depends! PMID- 22094959 TI - A polyoxometalate-based single-molecule magnet with an S = 21/2 ground state. AB - Ligand modification transforms a polyoxometalate-anchored cubane-type [Mn(III)(3)Mn(IV)O(4)] core into a centrosymmetric [Mn(III)(6)Mn(IV)O(8)] di cubane cluster, and restores the slow magnetization relaxation characteristics typical for [Mn(4)O(4)] cubane-based single-molecule magnets. PMID- 22094961 TI - Advanced topography-guided (OcuLink) treatment of irregular astigmatism after epikeratophakia in keratoconus with the WaveLight excimer laser. AB - PURPOSE: To evaluate the feasibility, safety, and predictability of treatment for high irregular astigmatism with advanced topography-guided laser epithelial keratomileusis in symptomatic eyes after epikeratophakia (EP) for keratoconus. METHODS: In a prospective case series, 10 consecutive eyes (10 patients) with high irregular astigmatism after epikeratophakia for keratoconus received OcuLink laser-assisted subepithelial keratectomy (LASEK) using the Allegretto Wave excimer laser. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifestation and refraction, corneal topographic examination with asphericity, and regularity were evaluated. All patients could not tolerate contact lens wear and had subjective symptoms. RESULTS: The UCVA improved from 0.61 +/- 0.27 logarithm of the minimum angle of resolution (logMAR) (range, 0.3 1.0 logMAR) to 0.27 +/- 0.07 logMAR (range, 0.2-0.4 logMAR), and the BSCVA improved from 0.25 +/- 0.14 to 0.15 +/- 0.09 logMAR (range, 0-0.3 logMAR) at 6 months after surgery. One patient had reduced UCVA (1 line), but no patients had reduced BSCVA. The refractive cylinder improved from -3.82 +/- 2.43 diopters (D) (range, -0.75 to -7.75 D) to -1.43 +/- 0.95 D (range, -0.25 to -2.50 D). The index of surface variance (an indicator of corneal surface irregularity) reduced from 115.1 +/- 21.1 (range, 90-153) to 68.4 +/- 18.2 (range, 39-95). Subjective symptoms, such as glare, halos, ghost images, starbursts, and monocular diplopia, were either not present or obviously alleviated. CONCLUSIONS: Advanced topography guided (OcuLink) LASEK can significantly reduce irregular astigmatism and increase the UCVA and BSCVA. PMID- 22094960 TI - Initial risk assessment for pulmonary hypertension in patients with COPD. AB - BACKGROUND: Pulmonary hypertension (PH) is a comorbidity associated with increased mortality in chronic obstructive pulmonary disease (COPD) patients. It is not known which clinical markers are predictive of PH in COPD. The goal of this study was to develop a clinical tool to identify patients who should be sent for initial screening with echocardiography. METHODS: Of 127 patients screened, 94 primary-care patients with COPD were enrolled. All underwent full pulmonary function testing, 6-minute walk distance (6MWD), exercise oximetry, Saint George's Respiratory Questionnaire, and transthoracic echocardiography. Eighty six patients had measurable pulmonary artery pressures (PAP) on echocardiography. Elevated PAP was defined as a systolic PAP > 35 mmHg. RESULTS: Pre- and post bronchodilator FEV(1) (P = 0.04 and P = 0.03, respectively), exercise oxyhemoglobin desaturation (P = 0.003), and 6MWD (P = 0.004) were associated with elevated PAP on univariate analysis. Diffusion capacity was lower but did not reach statistical significance (P = 0.07). In multivariate analysis, statistically significant independent variables were >3% decrease in exercise oxyhemoglobin saturation and decline in prebronchodilator FEV(1) (P = 0.01 and P = 0.04, respectively). A composite prediction model was developed that assigned one point for each of the following: age > 55 years, oxyhemoglobin desaturation > 3%, prebronchodilator FEV(1) < 50% predicted, and 6MWD < 1175 ft. Prevalence rates of elevated PAP were 32% for a score of 0-1 (low risk), 68% for a score of 2 (moderate risk), and 78% for a score of 3-4 (high risk). The composite score exhibited a strong trend with elevated PAP prevalence (Cochrane-Armitage trend statistic P = 0.001). CONCLUSION: A simple prediction tool using routine office based parameters can be used to identify COPD patients at high risk for elevated PAP and initiate the first step in screening for PH with echocardiography. It is important that right heart catheterization be performed to confirm the diagnosis and guide treatment decisions. PMID- 22094962 TI - Multigene expression in vivo: supremacy of large versus small terminators for T7 RNA polymerase. AB - Designing and building multigene constructs is commonplace in synthetic biology. Yet functional successes at first attempts are rare because the genetic parts are not fully modular. In order to improve the modularity of transcription, we previously showed that transcription termination in vitro by bacteriophage T7 RNA polymerase could be made more efficient by substituting the standard, single, TPhi large (class I) terminator with adjacent copies of the vesicular stomatitis virus (VSV) small (class II) terminator. However, in vitro termination at the downstream VSV terminator was less efficient than at the upstream VSV terminator, and multigene overexpression in vivo was complicated by unexpectedly inefficient VSV termination within Escherichia coli cells. Here, we address hypotheses raised in that study by showing that VSV or preproparathyroid hormone (PTH) small terminators spaced further apart can work independently (i.e., more efficiently) in vitro, and that VSV and PTH terminations are severely inhibited in vivo. Surprisingly, the difference between class II terminator function in vivo versus in vitro is not due to differences in plasmid supercoiling, as supercoiling had a minimal effect on termination in vitro. We therefore turned to TPhi terminators for "BioBrick" synthesis of a pentameric gene construct suitable for overexpression in vivo. This indeed enabled coordinated overexpression and copurification of five His-tagged proteins using the first construct attempted, indicating that this strategy is more modular than other strategies. An application of this multigene overexpression and protein copurification method is demonstrated by supplying five of the six E. coli translation factors required for reconstitution of translation from a single cell line via copurification, greatly simplifying the reconstitution. PMID- 22094963 TI - Immature muscle precursors are a source of interferon-beta in myositis: role of Toll-like receptor 3 activation and contribution to HLA class I up-regulation. AB - OBJECTIVE: To investigate the production of type I interferon (IFN) by myoblasts and to identify its cell source and the link to Toll-like receptor (TLR) and C type lectin receptor (CLR) expression and function in myositis biopsy sections. METHODS: Production of IFNbeta was assessed in cultured myoblasts after stimulation with the TLR-3 agonist poly(I-C) or with cytokines involved in Th1 and Th17 differentiation. Expression of HLA class I molecules by myoblasts was analyzed by fluorescence-activated cell sorting after activation of TLR-3 and IFNbeta neutralization. In muscle biopsy samples from patients with polymyositis or dermatomyositis, expression of IFNbeta, CD56 (a marker of immature muscle precursors), and HLA class I was analyzed using immunohistochemistry. Inflammatory infiltrates were characterized for the expression of myeloid dendritic cells (DCs), their associated CLRs, and the products of activated DCs, interleukin-12 (IL-12), and IL-23. RESULTS: In cultured myoblasts, stimulation of TLR-3 induced the production of IFNbeta when combined with IFNgamma and up regulated the expression of HLA class I molecules, which was decreased after IFNbeta blockade. In myositis biopsy tissues, immature muscle precursors overexpressing HLA class I were identified as a source of IFNbeta. CLRs associated with myeloid DCs were broadly expressed in inflammatory infiltrates, in association with IL-12 and IL-23, and with immature muscle precursors. CONCLUSION: Immature muscle precursors may represent a local source of IFNbeta and the target of an immune response involving activated DCs associated with the expression of CLRs and of IL-12 and IL-23, which are implicated in T cell polarization. In turn, such local production of IFNbeta after TLR-3 activation in the presence of the Th1 cytokine IFNgamma may explain HLA class I overexpression in myositis. PMID- 22094964 TI - The influence of reversible trianionic pincer OCO(3-)MU-oxo Cr(IV) dimer formation ([Cr(IV)]2(MU-O)) and donor ligands in oxygen-atom-transfer (OAT). AB - The oxygen-atom-transfer (OAT) from [(t)BuOCO]Cr(V)(O)(THF) (2) (where (t)BuOCO = [2,6-C(6)H(3)(6-(t)BuC(6)H(3)O)(2)](3-), THF = tetrahydrofuran) to triphenylphosphine (PPh(3)) in THF produces [(t)BuOCO]Cr(III)(THF)(3) (1) and triphenylphosphine oxide (OPPh(3)) at a rate of 69.5(+/-1.9) M(-1) s(-1) (22 degrees C). Identical rate constants were attained when acetonitrile (MeCN) and dichloromethane/THF (CH(2)Cl(2)/THF) were used as solvents. Electron paramagnetic resonance (EPR) data shows that the six-coordinate complex, [(t)BuOCO]Cr(V)(O)(THF)(2) (2a) forms upon addition of THF to 2, suggesting 2a as the active OAT species in THF. Similarly, addition of OPPh(3) has no influence on the rate of OAT, but the addition of triphenylphosphorus ylide (CH(2)PPh(3)) to form [(t)BuOCO]Cr(V)(O)(CH(2)PPh(3)) (4) prevents OAT to PPh(3). In CH(2)Cl(2), a [Cr(IV)](2)(MU-O) intermediate forms during the OAT from 2 to PPh(3). The OAT from {[(t)BuOCO]Cr(IV)(THF)}(2)(MU-O) (3) to PPh(3) reveals a zero-order dependence in PPh(3) indicating the dimer must first dissociate prior to OAT. The decay of 3versus time does not follow first-order kinetics due to the formation of a [(t)BuOCO]Cr(III)(THF) species (5) that inhibits the dissociation of 3. The change in concentration of 3versus time during OAT was simulated to obtain approximate rate constants. PMID- 22094965 TI - Patient-reported outcomes in adult survivors with single-ventricle physiology. AB - OBJECTIVES: Data on patient-reported outcomes (PROs) in patients with single ventricle physiology (SVP) are scarce. We sought (1) to describe the perceived health status, quality of life, symptoms of anxiety and depression, and sense of coherence in adult survivors with SVP, (2) to compare PROs across functional classes, and (3) to compare PROs between patients and controls. METHODS: A case control study in two adult congenital heart programmes with 62 adult survivors with SVP were matched to 172 healthy controls. A wide range of PROs were measured using validated questionnaires. The treating physician classified patients according to the Ability Index. RESULTS: Patients with SVP have a good functional status. Patients in Ability Index class I consistently reported the best scores, similar to those of healthy controls. Negative associations were found between functional class and outcomes of perceived health and quality of life. For patients in Ability Index class II and III, PROs were poorer. CONCLUSIONS: PROs in patients with SVP are generally good. PMID- 22094966 TI - Calcium effects on superoxide dismutase and catalase of the rabbit urinary bladder muscle and mucosa. AB - PURPOSE: Superoxide dismutase (SOD) and catalase are two important antioxidant mechanisms that work together to reduce free radical damage. Intracellular free calcium in smooth muscle can change rapidly and many enzymes can be affected. The sensitivity of SOD and catalase activity to calcium was determined in both rabbit bladder smooth muscle and mucosa. MATERIALS AND METHODS: Calcium sensitivity was analyzed by determining SOD and catalase activity in muscle and mucosa at the following calcium concentrations: 0 (in the presence of 1 mM EGTA), 1 and 5 mM CaCl(2). RESULTS: SOD: EGTA resulted in increased SOD activity of bladder smooth muscle, whereas both 1 and 5 mM calcium significantly decreased SOD activity. EGTA had no effect on SOD activity of the mucosa whereas 1 and 5 mM calcium decreased SOD activity of the muscle. Catalase: 1 mM calcium resulted in decreased catalase activity of the muscle and no change in the activity of the mucosa, whereas 5 mM calcium resulted in increased catalase activity of the mucosa but no change in the activity of the muscle. DISCUSSION: Mucosa showed more SOD and catalase activity than the muscle. Both SOD and catalase showed differing sensitivities to EGTA and calcium. PMID- 22094967 TI - [Older emergency patients benefit from geriatric assessment]. PMID- 22094968 TI - [Cancer, thromboembolia and antithrombotic therapy: is there an anticoagulant of choice?]. PMID- 22094969 TI - [Validation of patients' knowledge after informed consent prior to coronary angiography]. AB - BACKGROUND AND OBJECTIVE: The informed consent of the patient is required before any medical intervention can be done. The impact of the provided information on the subsequent knowledge of the patient is regularly questioned. In the present investigation we aimed to determine the knowledge of the patients about invasive coronary angiography (CA) after they had been optimally vs. standard vs. not at all informed. PATIENTS AND METHODS: 300 consecutive patients who were admitted for planned CA were included. Of these, 150 in-patients were informed by especially trained physicians one day before CA and 50 out-patients were informed by their general practitioner or cardiologist several days before admission. 100 in-patients were included before they were informed. In a standardized interview the predefined knowledge of the patients was assessed by an independent physician before CA in previously informed patients and after hospital admission in non informed patients. RESULTS: The differences in knowledge between informed in- and out-patients were low. Especially their knowledge about potential complications was not different. Generally, patients could remember less serious complications better than life-threatening ones. Two previously informed patients (1 %) affirmed that they were not informed. The knowledge of non-informed patients was much lower than the knowledge of patients who had been informed. CONCLUSION: The knowledge and remembrance of patients after having detailed information about medical interventions is limited. Optimization of the informative interview did not really improve this knowledge. In contrast to non-informed patients the provided information did, however, increase the knowledge. PMID- 22094971 TI - [74 year-old man with hypertension and angina pectoris. Single coronary artery]. PMID- 22094970 TI - [The Dunbar's syndrome: renaissance of a controversial disease pattern]. AB - HISTORY AND ADMISSION FINDINGS: A 79-year-old woman (BMI 23) presented with postprandial, occasionally epigastric, occasionally diffuse abdominal pain. INVESTIGATIONS: No pathologic findings in the physical examination and in the chemical analysis.Continuative examinations: Gastroscopy revealed a mild, nonreactive gastritis which was alleged not to be the cause of the symptoms. In ultrasonography arteriosclerotic lesions were seen, which led to the differential diagnosis of compensated angina abdominalis. On that assumption a CT-angiography was performed, which revealed a typical focal narrowing of the celiac axis about 1,5 cm distal of its origin in combination with hypertrophic collaterals between the celiac axis and the upper mesenteric artery. DIAGNOSIS, TREATMENT AND COURSE: In view of all findings, the diagnosis of Dunbar's syndrome was established. Since the symptoms were moderate, no further therapy was carried out. CONCLUSION: Dunbar's syndrome is caused by deep crossing of the median arcuate ligament resulting in compression of the proximal celiac axis resulting in a characteristic hooked appearance. Since a good collateralisation between the celiac axis and the superior mesenteric artery can be found, only about one percent of patients display symptoms (postprandial pain, sometimes weight loss). Typical patients are 20-40 year-old women. Although the diagnosis can be difficult and symptoms are rare, the Dunbar's syndrome, if typical morphologic findings an epigastric postprandial pain are present, is a relevant differential diagnosis. PMID- 22094972 TI - [Augmented reality: merge of reality and virtuality in medicine]. PMID- 22094973 TI - [Catheter ablation of paroxysmal atrial fibrillation: extended recommendations considering safety improvements of pulmonary vein isolation with a cryoballoon- Case 11/2011]. AB - HISTORY AND ADMISSION FINDINGS: A 71-year-old, male patient was referred to our clinic for paroxysmal palpitations with dyspnoe and fatigue since four years despite pharmacological treatment with flecainide and bisoprolol. INVESTIGATIONS: A paroxysmal atrial fibrillation was documented in a 24-hour Holter recording. A bicycle ergometry showed a hypertensive reaction during exercise without any sign of coronary insufficiency. Intracardiac thrombi could by excluded by transesophageal echocardiography. DIAGNOSIS, TREATMENT AND COURSE: The diagnosos of a drug-refractory paroxysmal atrial fibrillation was made and cryoballoon pulmonary vein isolation was performed. A follow-up 3 months after the ablation disclosed a freedom from atrial fibrillation documented in 7-day Holter recording. CONCLUSIONS: Compared to pharmacological rhythm control, interventional treatment has been established as more effective therapy for paroxysmal atrial fibrillation. However, patients should be referred to the ablation early enough to avoid structural atrial remodeling and thus transition into persistent or permanent atrial fibrillation. New technical developments e.g. cryoballoon catheter-system simplifies the procedure and has been reported to be effective and safe to use for circumferential pulmonary vein isolation. Should the very promising preclinical data on efficacy and safety of cryothermal energy ablation be confirmed by results of ongoing, controlled trials, the catheter ablation may become the fist-line treatment for all patients with paroxysmal atrial fibrillation. PMID- 22094974 TI - Pharmacoinvasive therapy for ST elevation myocardial infarction in China: a pilot study. AB - Most patients with acute ST-elevation myocardial infarction (STEMI) cannot receive timely primary percutaneous coronary intervention (PCI) because of lack of facilities or delays in patient transfer or catheterization team mobilization. In these patients, early routine post-thrombolysis PCI might be a reasonable, useful strategy. This study investigated feasibility and safety of early PCI after successful half-dose alteplase reperfusion in a Chinese population. Patients with STEMI received half-dose alteplase if expected time delay to PCI was >=90 min. Patients who reached clinical criteria of successful thrombolysis reperfusion were recommended to undergo diagnostic angiography within 3-24 h after thrombolysis. Patients with residual stenosis >=70% in the infarct-related artery underwent PCI, regardless of flow or patency status. Epicardial arterial flow was assessed using thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame count (CTFC). Myocardial perfusion was assessed using myocardial blush grade (MBG) and TIMI myocardial perfusion frame count (TMPFC). Forty-nine patients were enrolled and underwent diagnostic angiography 3-11.3 h (median 6.5 h) after thrombolysis. Forty-six patients underwent PCI. No procedure-related complications occurred, except two patients who had no reflow after PCI. Twenty two (47.8%) patients had TIMI grade 3 flow before PCI and 33 (71.7%) after PCI. CTFC was significantly improved after PCI (48.5 +/- 32.1 vs. 37.9 +/- 25.6, P = 0.01). MBG and TMPFC exhibited a similar improving trend after PCI, and the best myocardial perfusion tended to be achieved 3-12 h after lysis. During the 30-day follow-up, there were two deaths. The composite end point of death, cardiogenic shock, heart failure, reinfarction, and recurrent ischemia occurred in four patients. TIMI minor bleeding occurred in four patients. No TIMI major bleeding and stroke occurred. Early routine PCI after half-dose alteplase thrombolysis in Chinese population appears feasible. A larger clinical trial should be designed to further elucidate its efficacy and safety. Early PCI after thrombolysis in STEMI: The EARLY-PCI pilot feasibility study, ChiCTR-TNC-11001363. PMID- 22094976 TI - Corynebacterium glutamicum as a potent biocatalyst for the bioconversion of pentose sugars to value-added products. AB - Corynebacterium glutamicum, the industrial microbe traditionally used for the production of amino acids, proved its value for the fermentative production of diverse products through genetic/metabolic engineering. A successful demonstration of the heterologous expression of arabinose and xylose utilization genes made them interesting biocatalysts for pentose fermentation, which are the main components in lignocellulosic hydrolysates. Its ability to withstand substantial amount of general growth inhibitors like furfurals, hydroxyl methyl furfurals and organic acids generated from the acid/alkali hydrolysis of lignocellulosics in growth arrested conditions and its ability to produce amino acids like glutamate and lysine in acid hydrolysates of rice straw and wheat bran, indicate the future prospective of this bacterium as a potent biocatalyst in fermentation biotechnology. However, the efforts so far on these lines have not yet been reviewed, and hence an attempt is made to look into the efficacy and prospects of C. glutamicum to utilize the normally non-fermentable pentose sugars from lignocellulosic biomass for the production of commodity chemicals. PMID- 22094977 TI - Biosynthesis and function of gliotoxin in Aspergillus fumigatus. AB - Gliotoxin (GT) is the prototype of the epidithiodioxopiperazine (ETP)-type fungal toxins. GT plays a critical role in the pathobiology of Aspergillus fumigatus. It modulates the immune response and induces apoptosis in different cell types. The toxicity has been attributed to the unusual intramolecular disulfide bridge, which is the functional motif of all ETPs. Because of the extraordinary structure and activity of GT, this fungal metabolite has been the subject of many investigations. The biosynthesis of GT involves unprecedented reactions catalysed by recently discovered enzymes. Here, we summarize the recent progress in elucidating the GT biosynthetic pathway and its role in virulence. PMID- 22094978 TI - Achieving nitrite accumulation in a continuous system treating low-strength domestic wastewater: switchover from batch start-up to continuous operation with process control. AB - Although biological nitrogen removal via nitrite is recognized as one of the cost effective and sustainable biological nitrogen removal processes, nitrite accumulation has proven difficult to achieve in continuous processes treating low strength nitrogenous wastewater. Partial nitrification to nitrite was achieved and maintained in a lab-scale completely stirred tank reactor (CSTR) treating real domestic wastewater. During the start-up period, sludge with ammonia oxidizing bacteria (AOB) but no nitrite-oxidizing bacteria (NOB) was obtained by batch operation with aeration time control. The nitrifying sludge with the dominance of AOB was then directly switched into continuous operation. It was demonstrated that partial nitrification to nitrite in the continuous system could be repeatedly and reliably achieved using this start-up strategy. The ratio of dissolved oxygen to ammonium loading rate (DO/ALR) was critical to maintain high ammonium removal efficiency and nitrite accumulation ratio. Over 85% of nitrite accumulation ratio and more than 95% of ammonium removal efficiency were achieved at DO/ALR ratios in an optimal range of 4.0-6.0 mg O(2)/g N d, even under the disturbances of ammonium loading rate. Microbial population shift was investigated, and fluorescence in situ hybridization analysis indicated that AOB were the dominant nitrifying bacteria over NOB when stable partial nitrification was established. PMID- 22094979 TI - Applications of microbial fermentations for production of gluten-free products and perspectives. AB - A gluten-free (GF) diet is recognised as being the only accepted treatment for celiac disease-a permanent autoimmune enteropathy triggered by the ingestion of gluten-containing cereals. The bakery products available in today's gluten-free market are characterised by lower palatability than their conventional counterparts and may lead to nutritional deficiencies of vitamins, minerals and fibre. Thus, the production of high-quality gluten-free products has become a very important socioeconomical issue. Microbial fermentation by means of lactic acid bacteria and yeast is one of the most ecological/economical methods of producing and preserving food. In this review, the role of a fermentation process for improving the quality of GF products and for developing a new concept of GF products with nutraceutical and health-promoting characteristics will be examined. PMID- 22094980 TI - Biotransformation of BMOV in the presence of blood serum proteins. AB - The interaction of the potent anti-diabetic agent bis(maltolato)oxidovanadium(IV) (BMOV) with some proteins of blood serum was studied by EPR spectroscopy, pH potentiometry and DFT calculations. The formation of cis-VO(ma)(2)(hTf), cis VO(ma)(2)(HSA) and cis-VO(ma)(2)(IgG), their role in the biotransformation in vivo and the mechanism of transport of BMOV in blood are discussed. PMID- 22094981 TI - Asthma and suicide: current knowledge and future directions. AB - The prevalence of asthma has risen dramatically, especially among youth, in recent years, and asthma is now among the most common chronic conditions. Recent studies suggest a relationship between asthma and suicidal ideation, suicide attempt, and death by suicide. This paper reviews the literature, summarizes the weight of evidence, and discusses the clinical implications and future directions for research. PMID- 22094982 TI - A review of the association between depression and insulin resistance: pitfalls of secondary analyses or a promising new approach to prevention of type 2 diabetes? AB - We review the validity of the evidence for an association between depression and the risk of insulin resistance (IR). We describe the potentially plausible biological and behavioral mechanisms that explain how depression increases the risk of IR and consequent overt diabetes. We have identified gaps in the literature to guide future research. Evidence for bidirectional associations between depression and IR is inconsistent. Results showing positive associations between depression and IR are derived from cross-sectional studies, whereas negative findings are typically reported in cohort studies. On the other hand, tentative trial evidence suggests that the effective treatment of depression can improve IR, and that lifestyle programs improve IR and reduce depressive symptoms. These emerging themes could lead to potential new multidisciplinary approaches to preventing diabetes. PMID- 22094983 TI - Effects of continuous haemofiltration on serum enzyme concentrations, endotoxemia, homeostasis and survival in dogs with severe heat stroke. AB - AIM: To examine the effectiveness of continuous haemofiltration as a treatment for severe heat stroke in dogs. METHODS: Dogs were randomly allocated to a control or continuous haemofiltration group (both n=8). Heat stroke was induced by placing anaesthetised dogs in a high temperature cabin simulator. Upon confirmation of heat stroke (rectal temperature>42 degrees C, mean arterial pressure (MAP) decrease>25 mmHg), dogs were removed from the chamber and continuous haemofiltration was initiated and continued for 3h for dogs in the continuous haemofiltration group. Dogs in the control group were observed at room temperature. RESULTS: Rectal temperature, haemodynamics, pH, blood gases and electrolyte concentrations rapidly returned to baseline in the continuous haemofiltration group, but not the control group. After 3h, rectal temperature was 36.68+/-0.51 degrees C in the continuous haemofiltration group and 39.83+/ 1.10 degrees C in the control group (P<0.05). Continuous haemofiltration prevented endotoxin and all serum enzyme concentrations from increasing and caused malondialdehyde concentrations to decrease. After 3h, endotoxin concentrations were 0.14+/-0.02 EU ml(-1) in the continuous haemofiltration group and 0.23+/-0.05 EU ml(-1) in the control group (P=0.003), while malondialdehyde concentrations were 4.86+/-0.61 mmol l(-1) in the continuous haemofiltration group and 8.63+/-0.66 mmol l(-1) in the control group (P<0.001). Five dogs died in the control group within 3h, whereas no dogs died in the continuous haemofiltration group. CONCLUSIONS: Continuous haemofiltration rapidly reduced body temperature, normalised haemodynamics and electrolytes, improved serum enzyme concentrations and increased survival in dogs with heat stroke. Continuous haemofiltration may be an effective treatment for heat stroke. PMID- 22094984 TI - Hands-on defibrillation: theoretical and practical aspects of patient and rescuer safety. AB - Defibrillators are used to treat many thousands of people each year using very high voltages, but, despite this, reported injuries to rescuers are rare. Although even a small number of reported injuries is not ideal, the safety record of the defibrillator using the current protocol is widely regarded as being acceptable. There is increasing evidence that clinical outcome is significantly improved with continuous chest compressions, but defibrillation is a common cause of interruptions; even short interruptions, such as those associated with defibrillation, may detrimentally affect the outcome. This has led to discussions regarding the possibility of continuing chest compressions during defibrillation; a process involving a rescuer working in close proximity to voltages of up to 5000 V. Not only do voltages of this magnitude have significant implications for the rescuer performing chest compressions, but there are also risks to other rescuers in the proximity, the patient and other bystanders. Clearly any deviation from accepted practice should only be undertaken following careful consideration of the risks and benefits to the patient, rescuers and others. This review summarises the physical principles of electrical risk and identifies ways in which these could be managed. In doing so, it is hoped that in future it may be possible to deliver continuous and safe manual chest compressions during defibrillator discharge in order to improve patient outcome. PMID- 22094986 TI - Cytokines: IL-17C joins the family firm. PMID- 22094987 TI - Dendritic cells: Choosing the right presentation. PMID- 22094985 TI - TLR-dependent T cell activation in autoimmunity. AB - Autoimmune disease can develop as a result of a breakdown in immunological tolerance, leading to the activation of self-reactive T cells. There is an established link between infection and human autoimmune diseases. Furthermore, experimental autoimmune diseases can be induced by autoantigens that are administered together with complete Freund's adjuvant, which contains killed Mycobacterium tuberculosis; in some cases, these bacteria can be replaced by individual pathogen-associated molecular patterns (PAMPs). Exogenous PAMPs and endogenous danger signals from necrotic cells bind to pattern recognition receptors (including Toll-like receptors) and activate signalling pathways in innate immune cells and in T cells. This leads to pro-inflammatory cytokine production and T cell activation, which are now considered to be major factors in the development of autoimmunity. PMID- 22094990 TI - Deformity of talus and calcaneous in congenital clubfoot: an anatomical study. AB - Clubfoot is a complex congenital deformity. Midtarsal joint is a key point to understand the deformity in clubfoot as a consequence of the malalignment of the osseous columns. Talar and calcaneal deformities affecting the normal alignment of the medial and lateral osseous columns in the foot can be the factors that determine the difficulty in the management of clubfoot. We report observations of two clubfeet of one stillborn. Our observations in the head of the talus report two different articular areas: the histological section of medial area facing the navicular shows active articular cartilage and the lateral area shows an atrophic articular cartilage suggesting a difference between the anatomical declination angles of the talus from a functional declination angle. Observing the calcaneous, we report a twisting rotational deformity along the longitudinal axis of the calcaneous. These observations may contribute to a better understanding of the clubfoot relapse, and also the treatment of complicated cases of clubfeet. PMID- 22094988 TI - Strategies to discover regulatory circuits of the mammalian immune system. AB - Recent advances in technologies for genome- and proteome-scale measurements and perturbations promise to accelerate discovery in every aspect of biology and medicine. Although such rapid technological progress provides a tremendous opportunity, it also demands that we learn how to use these tools effectively. One application with great potential to enhance our understanding of biological systems is the unbiased reconstruction of genetic and molecular networks. Cells of the immune system provide a particularly useful model for developing and applying such approaches. Here, we review approaches for the reconstruction of signalling and transcriptional networks, with a focus on applications in the mammalian innate immune system. PMID- 22094989 TI - Throwing transcription for a loop: expression of the genome in the 3D nucleus. AB - The functional output of the genome is closely dependent on its organization within the nucleus, which ranges from the 10-nm chromatin fiber to the three dimensional arrangement of this fiber in the nuclear space. Recent observations suggest that intra- and inter-chromosomal interactions between distant sequences underlie several aspects of transcription regulatory processes. These contacts can bring enhancers close to their target genes or prevent inappropriate interactions between regulatory sequences via insulators. In addition, intra- and inter-chromosomal interactions can bring co-activated or co-repressed genes to the same nuclear location. Recent technological advances have made it possible to map long-range cis and trans interactions at relatively high resolution. This information is being used to develop three-dimensional maps of the arrangement of the genome in the nucleus and to understand causal relationships between nuclear structure and function. PMID- 22094991 TI - Ewing sarcoma of the tibia mimicking fibrous dysplasia. AB - Ewing sarcoma (ES) family of tumors is the second most common primary bone malignancy in children. It usually presents as an aggressive looking lesion often located in the meta-diaphyseal region of long bones, with bone destruction, permeation, cortical thinning and/or destruction, periosteal reaction, and large soft-tissue mass. The purpose of this study is to illustrate the occurrence of a fibrous dysplasia (FD)-appearing ES of the tibia. These cases underscore the potential difficulties encountered in the diagnosis of ES. In this study, we performed a retrospective review of children who presented with an otherwise benign-appearing lesion of the tibia, suggestive of FD, which proved to be ES after biopsy. As a result, all patients presented with a history of indolent lower extremity pain of several months of duration, without significant swelling or constitutional symptoms. Plain films revealed an otherwise benign-appearing/FD like lesion without bone destruction and mild cortical thinning, little or no periosteal reaction. Magnetic resonance imaging revealed the intramedullary extension of the lesion without significant cortical or periosteal involvement and no soft tissue mass. Lesions were hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging. All patients underwent open incisional biopsy and after cytogenetic and molecular studies, the diagnosis of ES was confirmed. We conclude that ES is a deadly malignant tumor if left untreated or if mismanaged. Although it usually presents as an aggressive-looking lesion, at times it may mimic FD and has a benign-looking appearance, making the diagnosis unlikely and challenging. Summation of these cases demonstrates that the potential reasons for misdiagnoses include a low level of suspicion, an atypical site occurrence, a benign radiographic appearance, and a lack of or insufficient histologic specimens. PMID- 22094992 TI - Risk of esophageal cancer in diabetes mellitus: a meta-analysis of observational studies. AB - OBJECTIVE: Inconsistent findings from observational studies have prolonged the controversy over the effects of history of diabetes mellitus (DM) on the risk of esophageal cancer (EC). We conducted a meta-analysis of epidemiologic studies to evaluate the association of a history of DM with the risk of EC. METHODS: We identified studies by a literature search of MEDLINE (from 1 January 1966) and EMBASE (from 1 January 1974), through 28 Feburary 2011, and by searching the reference lists of pertinent articles. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. All statistical tests were two-sided. RESULTS: A total of 17 studies (6 case-control studies and 11 cohort studies) fulfilled the inclusion and exclusion criteria. Compared with non-diabetic individuals, diabetic individuals had a modestly increased risk of EC (SRRs 1.30, 95% CI: 1.12-1.50), with significant heterogeneity among studies (p = 0.042). In stratified analysis, the SRRs of EC were 1.28 (1.10-1.49) for diabetic men and 1.07 (95% CI, 0.71-1.62) for diabetic women, respectively. In addition, DM was associated with an increased risk of esophageal adenocarcinoma (SRR 2.12, 95% CI 1.01-4.46). There was no significant publication bias (p = 0.127 for Begg's adjusted rank correlation test and p = 0.629 for Egger's regression test). CONCLUSION: These findings support the hypothesis that men with diabetes may have a modestly increased risk of EC, while diabetic women were not the case. PMID- 22094993 TI - Clinical use of PET/CT in peritoneal carcinomatosis from colorectal cancer. AB - BACKGROUND/AIMS: Peritoneal carcinomatosis (PC) from colorectal cancer has been associated with poor survival but new approaches and postoperative chemotherapy have improved survival. The purpose of this study was to evaluate the clinical utility of imaging in cases of PC from colorectal cancer. METHODOLOGY: This is a retrospective single-institution study which examined 23 patients with colorectal cancer who underwent positron emission tomography (PET), computed tomography (CT) and received a final diagnosis PC in our institute between 2005 and 2010. RESULTS: PET/CT detected PC in 19 of 23 cases (82.6%), whereas CT detected PC in 6 of 20 cases (30%). Four cases of PC were FDG-negative, all with maximal size <10mm, representing smaller tumors. FDG-negative PC was diffuse in 3 cases and nodular in 1. The distributed spotty uptake of FDG-negative PC was harder to detect. Diagnostic detection of PC was only achieved in 3 of 23 cases (13%). In the remaining cases, clinical diagnosis was metastasis to lymph nodes, recurrence, or normal FDG uptake by intestine. CONCLUSIONS: PET/CT offers efficient detection of PC and has the potential to improve clinical diagnosis when coupled with an understanding of the pathways of flow for ascitic fluid and peritoneal seeding. PMID- 22094994 TI - Risk factors of SFSS in adult-to-adult living donor liver transplantation using the right liver: a single-center analysis of 217 cases. AB - BACKGROUND/AIMS: Small-for-size Syndrome (SFSS) in adult-adult living right lobe liver transplantation (A-ALRLT) remains the greatest limiting factor for the expansion of using segmental liver transplantation and the major cause of worse short-term prognoses after LDLT. The causes of SFSS are not clear, so in this study we approached the risk factors of the SFSS. METHODOLOGY: The study included 217 consecutive adult recipients that underwent living right lobe liver transplantation at our center. Cases were divided into two groups: 45 cases were determined as SFSS and 172 cases without SFSS within one month after transplantation. Preoperative factors like donor and recipient characteristics, operational data and postoperative factors were compared between the two groups. Factors possibly related to postoperative SFSS were also analyzed using logistic regression. RESULTS: After comparing the two groups, there was no significant difference in donor and recipient background characteristics and no differences were found between the two groups, except for portal inflow volume and MELD score which were much higher and GRWR and outflow volume were much lower in G1. Logistic regression analysis revealed four independent factors associated with SFSS development in right lobe graft: GRWR, MELD score, portal inflow volume and outflow capacity. CONCLUSIONS: Small GRWR, high MELD score, high portal inflow volume and low outflow capacity are four risk factors in A-ALRLT. PMID- 22094995 TI - Correlation between p16 expression and malignant risk of gastrointestinal stromal tumor: evidence from nine studies. AB - BACKGROUND/AIMS: The published data about p16 expression and its potential value in malignant risk of GIST patients seems inconclusive. To derive a more precise estimation of this relationship a meta-analysis was performed. METHODOLOGY: Studies were identified using PubMed and Embase. Inclusive criteria were GIST patients, evaluation of p16 expression and malignant risk. The odds ratios for positive rate of p16 in NIH very low risk group vs. NIH low risk group, for positive rate of p16 in NIH low risk group vs. NIH intermediate risk group, for positive rate of p16 in NIH intermediate risk group vs. NIH high risk group, and for positive rate of p16 in NIH very low risk/low risk group vs. NIH intermediate risk/high risk group, were calculated with 95% CI for each study as an estimation of potential value of p16 in malignant risk of GIST. RESULTS: A total of 9 studies including 817 patients were involved in this meta-analysis. The meta analyses of positive rate of p16 among NIH VL group vs. NIH L group vs. NIH I group vs. NIH H group did not attain significant differences, but the overall OR for positive rate of p16 in NIH VL+L group vs. NIH I+H group revealed that significantly elevated risks of positive p16 in NIH VL+L group were achieved. CONCLUSIONS: The results indicate p16 loss correlates with the increase of malignant risk for GIST and has a close relationship within the NIH I risk group and NIH H risk group. PMID- 22094996 TI - Novel biopsy forceps for diagnosis of biliary tract diseases during endoscopic retrograde cholangiopancreatography: a prospective comparative study with 90 degrees adjustable and conventional biopsy forceps. AB - BACKGROUND/AIMS: Recently, controllable biopsy forceps (MTW, D degrees sseldorf, Germany) have been developed. This biopsy forceps were 90 degrees adjustable. In the present study, the feasibility and efficacy of the controllable biopsy forceps were compared with those of conventional biopsy forceps in patients with biliary tract disease. METHODOLOGY: A total of 27 patients with biliary tract lesions were enrolled. We evaluated the procedure time, the sample tissue size and the diagnostic accuracy. In addition, the physicians performing the procedure rated their impressions about operability into 3 classes: excellent, fair and poor. RESULTS: The sensitivity in distinguishing benign from malignant lesions was 71.4% (15/21) for the 90 degrees adjustable type and 66.7% (14/21) for the conventional type. The accuracy rate was 77.8% (21/27) for the 90 degrees adjustable type and 74.0% (20/27) for the conventional type. In terms of operability as rated by each physician, the 'excellent' rate was given more frequently to the 90 degrees adjustable type 25.9% than for the conventional type 11.1% (p=0.047). CONCLUSIONS: This preliminary study showed that controllable biopsy forceps compared to conventional type biopsy forceps, despite a larger diameter, enables biopsy in a similar procedure time and its ease of use was rated better. PMID- 22094997 TI - Serum matrix metalloproteinase-9 is an early marker of pancreatic necrosis in patients with severe acute pancreatitis. AB - BACKGROUND/AIMS: To study the ability of matrix metalloproteinase-9 (MMP-9) to predict pancreatic necrosis (PN) in patients with severe acute pancreatitis (SAP). METHODOLOGY: From July 1, 2010 to December 31, 2010 patients diagnosed with SAP were included (n=35). Serum MMP-9, CRP and IL-6 were analyzed on days 1, 3, 5 and 7 of hospitalization to determine if they could predict the development of pancreatic necrosis. RESULTS: Of the 35 patients included, 12 (34.3%) had evidence of PN. Admission MMP-9 concentrations were significantly higher in patients with PN compared to subjects without PN (13.1+/-4.0 vs. 7.5+/-3.8, p<0.05). Receiver operating characteristic curves for PN revealed an area under the curve of 0.832 for admission MMP-9 (95% confidence interval 0.696-0.967, p=0.001). Elevated concentrations of MMP-9 on admission for pancreatic necrosis =9.35mg/L yielded a positive predictive value of 90.9% with a sensitivity of 91.7% and a specificity of 69.6%. Binary logistic regression indicated that MMP-9 was significantly associated with pancreatic necrosis (Odds ratios 25.1, 95% confidence interval 2.7-234.2; p=0.005). CONCLUSIONS: An elevation in serum MMP-9 within the first 24 hours of disease is strongly associated with the development of pancreatic necrosis. This finding may have important clinical implications and requires further investigation. PMID- 22094998 TI - What's good for the goose is good for the gander. Guiding principles for the use of financial incentives in health behaviour change. AB - BACKGROUND: The use of financial incentives or pay-for-performance programs for health care providers has triggered emerging interest in the use of financial incentives for encouraging health behaviour change. PURPOSE: This paper aims to identify key conditions under which the use of financial incentives for improvements in public health outcomes is most likely to be effective and appropriate. METHODS: We review recent systematic reviews on their effectiveness in changing health behaviour and identify existing moral concerns concerning personal financial incentives. RESULTS: Current evidence indicates that incentives can be effective in driving health behaviour change under certain provisos, while a number of misgivings continue to be deliberated on. We outline a number of key principles for consideration in decisions about the potential use of incentives in leading to public health improvements. CONCLUSION: These key principles can assist policy makers in making decisions on the use of financial incentives directed at achieving improvements in public health. PMID- 22094999 TI - Hyperbolic correlation between insulin sensitivity and insulin secretion fades away in lean subjects with superb glucose regulation. AB - The relationship between insulin sensitivity (Si) and insulin secretion (beta) was analyzed in 533 health examinees. The subjects underwent a 75 g oral glucose tolerance test, with plasma glucose (PG) and immunoreactive insulin (IRI) determined at fasting, 30 min and 120 min, and were classified according to the current criteria as normal glucose tolerance (NGT, n=328), non-diabetic hyperglycemia (NDH, n=113) including impaired fasting glucose and impaired glucose tolerance, and diabetes mellitus (DM, n=72). NGT was subdivided by fasting PG (FPG) tertile, <=4.9, 5.0-5.4 and 5.5-6.0 mM, into NGT(FPG1), NGT(FPG2) and NGT(FPG3), or by body mass index (BMI) tertile, <=21.8, 21.9-24.4 and >=24.5 kg/m2, into NGT(BMI1), NGT(BMI2) and NGT(BMI3). As an index of Si and beta, Matsuda index=10,000/sqrt[FPG.FIRI.2hPG.2hIRI] and deltaIRI0-30/deltaPG0 30, were employed respectively: FIRI, 2hPG and 2hIRI denote fasting IRI, 2h-post glucose PG and IRI, respectively. Correlation between Si and beta was evaluated by Spearman's rank correlation and the parameters for [beta]=a.[Si](b) were obtained by standardized major axis (SMA) regression. Si-beta correlation was strongest in NDH (Spearman's rho=-0.546, SMA regression r2=0.277), intermediate in DM (rho=-0.432, r2=0.193) and weakest in NGT (rho=-0.201, r2=0.039). Spearman's rho for the Si-beta correlation was significantly lower in NGT than in NDH (p=0.003). Si-beta correlation was significant in NGT(FPG3), NGT(FPG2) and NGT(BMI3), but not in NGT(FPG1), NGT(BMI2) and NGT(BMI1). The slope, b, was 1.184~-1.530 without significant differences between any groups. In conclusion, the hyperbolic Si-beta correlation was weaker in NGT than in NDH and absent in NGT subjects belonging to the lowest FPG or BMI tertile. PMID- 22095000 TI - One in five subjects with normal thyroid ultrasonography has altered thyroid tests. AB - The relation between thyroid ultrasonography and laboratory, and the relationship of thyroid volume with clinical and anthropometric parameters, are not well clarified. Aim of the study was to investigate normal and hypoechoic inhomogeneous not nodular thyroid gland in predicting thyroid tests, and to assess the correlation of thyroid volume with several clinical parameters. The series included 434 subjects (244 with normal thyroid ultrasonography, and 190 with hypoechoic-inhomogeneous thyroid) at their first evaluation. Subjects with normal ultrasonography and skewed tests were re-evaluated after one year. All subjects with normal ultrasound showed normal free-T4, while TSH was elevated in 9.8% of cases and thyroid antibodies were positive in another 9.8%. In patients with hypoechoic-inhomogeneous thyroid, free-T4 was low in 33.2%, TSH was elevated in 78.4% and thyroid antibodies were positive in 76.3%. Normal ultrasonography matched with normal tests in 81.1% of cases while hypoechoic-inhomogeneous thyroid in 9.5% (p<0.001). The re-evaluation of tests showed no significant difference. In subjects with both normal ultrasonography and tests, thyroid volume was correlated with age (p=0.001), weight (p=0.003), BMI (p=0.04), body surface area (p=0.002). Thyroid laboratory assessment was different between subjects with ultrasonographically normal or hypoechoic-inhomogeneous thyroid. Thyroid volume of thyroid diseases-free subjects was correlated with age, weight, BMI and body surface area, and this should be of interest to investigate the references of normality of thyroid size. PMID- 22095001 TI - Prediction of late (24-hour) radioactive iodine uptake using early (3-hour) uptake values in Japanese patients with Graves' disease. AB - Measurement of 24-hour radioactive iodine uptake (RAIU), which is commonly used to calculate the dose of radioiodine (RI) therapy, cannot be accomplished in a single day. The purpose of this study was to predict 24-hour RAIU from 3-hour RAIU in Japanese patients with Graves' disease, and to investigate other factors that could be used to predict 24-hour RAIU. A total of 66 Japanese patients (14 men and 52 women; age, 17-83 years) with Graves' disease who had undergone both 3 hour and 24-hour 123I RAIU measurements between January 2006 and September 2011 were included in this study. Stepwise multiple regression analyses were performed in order to identify factors that could be used to predict 24-hour RAIU. The investigated factors were gender, age, thyroid volume, TSH, free thyroxine (FT4), free triiodothyronine (FT3), serum creatinine, second generation assay TSH receptor antibody (TRAb2), antithyroid drugs discontinuation period (ADP), iodine restriction period and 3-hour RAIU. The ADP was converted to an ordinal scale ADP score (ADPS) for multiple regression analyses. Multiple regression analyses showed that 3-hour RAIU (P < 0.001), FT3 (P < 0.001) and ADPS (P < 0.001) were statistically significant predictive factors of 24-hour RAIU. The relationship between 24-hour RAIU (LU) and 3-hour RAIU (EU), FT3 and ADPS was: LU = 11.5 + 29.1 * log10 EU + 23.0 * log10 FT3 - 2.7 * ADPS (r = 0.82, P < 0.001). The present results indicate that prediction of LU from EU, FT3 and ADPS is feasible in Japanese patients with Graves' disease. PMID- 22095002 TI - Prolonged conversion of n-butyrate to n-butanol with Clostridium saccharoperbutylacetonicum in a two-stage continuous culture with in-situ product removal. AB - n-Butanol was produced continuously in a two-stage fermentor system with integrated product removal from a co-feed of n-butyric acid and glucose. Glucose was always required as a source of ATP and electrons for the conversion of n butyrate to n-butanol and for biomass growth; for the latter it also served as a carbon source. The first stage generated metabolically active planktonic cells of Clostridium saccharoperbutylacetonicum strain N1-4 that were continuously fed into the second (production) stage; the volumetric ratio of the two fermentors was 1:10. n-Butanol was removed continuously from the second stage via gas stripping. Implementing a two-stage process was observed to dramatically dampen metabolic oscillations (i.e., periodical changes of solventogenic activity). Culture degeneration (i.e., an irreversible loss of solventogenic activity) was avoided by periodical heat shocking and re-inoculating stage 1 and by maintaining the concentration of undissociated n-butyric acid in stage 2 at 3.4 mM with a pH auxostat. The system was successfully operated for 42 days during which 93% of the fed n-butyrate was converted to n-butanol at a production rate of 0.39 g/(L * h). The molar yields Y(n-butanol/n-butyrate) and Y(n-butanol/glucose) were 2.0, and 0.718, respectively. For the same run, the molar ratio of n-butyrate to glucose consumed was 0.358. The molar yield of carbon in n-butanol produced from carbon in n-butyrate and glucose consumed (Y(n-butanol/carbon) ) was 0.386. These data illustrate that conversion of n-butyrate into n-butanol by solventogenic Clostridium species is feasible and that this can be performed in a continuous system operating for longer than a month. However, our data also demonstrate that a relatively large amount of glucose is required to supply electrons and ATP for this conversion and for cell growth in a continuous culture. PMID- 22095003 TI - Exploring the provision of hospital trauma care for road traffic injury victims in Iran: a qualitative approach. AB - BACKGROUND: Identifying factors affecting the provision of trauma care is essential for improving the quality of care for road traffic injury (RTI) victims. The study aimed to explore the perceptions and experiences of trauma care among injured patients and health professionals to identify factors influencing an effective trauma care delivery at emergency departments (EDs) in Iran. METHODS: The study was conducted with a grounded theory approach. The study participants consisted of 15 health professionals and 20 injured patients. The data were collected via semi-structured interviews and were analyzed using constant comparative analysis method. RESULTS: Lack of a systematic approach to providing trauma care at EDs emerged as the core category. The leading factors in the development of the core category were unclear national policies and poor organization of care at the ED. Other major factors were contextual factors in the environment of the hospitals such as inappropriate structure and unsupportive environment and also factors specific to the context of Iran such as a rapid increase in the number of traumas. Professionals reacted to the prevailing conditions in ways that contributed to an ineffective trauma care, even though strategies employed by Emergency Medicine Physicians (EMPs) improved the quality of trauma care locally. CONCLUSIONS: Building a national trauma system, using available professional resources especially EMPs, and implementing low cost and evidence-based improvements such as establishing trauma teams and trauma training for staff working at the EDs on a regular basis is necessary in order to improve delivery of trauma care at the hospitals. PMID- 22095004 TI - Migration challenges among Zimbabwean refugees before, during and post arrival in South Africa. AB - BACKGROUND: Zimbabweans are immigrating to South Africa with a commonly cited reason being economic opportunities. Prospects of finding employment may be a significant reason to leave behind family, friends, and community, sources that buffer and offer social support against life's challenges. Currently, there is a dearth of research examining the motivators for Zimbabweans immigrating and the experiences encountered along the way and after arrival in South Africa. Such research is essential as large numbers of Zimbabweans may be at risk for emotional and physical trauma during this process. METHODS: Two gender specific focus group discussions, each lasting 90-minutes and consisting of homeless Zimbabwean refugees, were conducted in the Limpopo Province of South Africa. A semi-structured interview assessed for experiences in and reasons for leaving Zimbabwe, as well as experiences en-route and within South Africa. Discussions were audio-recorded, transcribed, and analyzed using consensual qualitative research and a constant comparison qualitative method. RESULTS: Three temporal themes were identified and included challenges and trauma experienced in Zimbabwe (pre-migration), during the immigration journey (mid-migration), and upon arrival in South Africa (post-migration). While there were some experiential differences, Zimbabwean men and women shared numerous traumatic commonalities. In addition to the themes, three subthemes contributing to reasons for leaving Zimbabwe, two subthemes of negative and traumatic experiences incurred mid-migration, and two post-migration subthemes of challenges were identified. CONCLUSIONS: Despite the difficulties encountered in their homeland, newly arrived Zimbabweans in South Africa may be exchanging old struggles for a new array of foreign and traumatic challenges. Reasons to immigrate and the psychological and physical toll of migration exacted at the individual and community levels are discussed. Recommendations advocating for culturally congruent mental health research, the training of culturally competent researchers and clinicians, and the development of policies that could influence the quality of life of Zimbabwean refugees are provided. PMID- 22095005 TI - The remote assessment of melanocytic skin lesions: a viable alternative to face to-face consultation. AB - BACKGROUND: The incidence of melanoma continues to rise in the Western world, prompting health care professionals to search for novel tools that may increase rates of early detection. Here we focus on one such tool: remote specialist diagnosis of melanocytic lesions utilising mobile-phone camera patient-generated clinical images. OBJECTIVE: We aim to test the hypothesis that patient-generated clinical images utilising mobile phones are of acceptable quality, and that digital image diagnostic outcomes are comparable with face-to-face (FTF) diagnostic outcomes. METHODS: Study participants were asked to photograph, using their mobile-phone camera any number of their own melanocytic naevi, and then upload these clinical images to a central server. Diagnostic accuracy of the management decision based on assessing these digital images was tested by comparing results from digital image assessment with results from FTF assessments. RESULTS: We provide evidence that suggests potential patients are capable of uploading good quality clinical images of melanocytic lesions for diagnostic purposes, and we show that good concordance rates can be achieved with respect to digital image and FTF diagnostic outcomes. With respect to the latter, exact agreement was found in 116 of 167 assessable lesions (69%). CONCLUSIONS: This work suggests that specialist remote diagnosis of patient-generated clinical images of melanocytic lesions utilising mobile-phone cameras may be a viable alternative to traditional FTF assessments. PMID- 22095006 TI - Recidivism rates among mentally ill inmates: impact of the Connecticut Offender Reentry Program. AB - This study compares data from the Connecticut Offender Reentry Program (CORP) and retrospective data for inmates who received standard treatment planning services from the Connecticut Department of Mental Health and Addictions Services (DMHAS). Analysis of DMHAS data investigated characteristics (demographic, psychiatric, and prison classification scores) and recidivism rates of 883 individuals. A program evaluation was later completed on a separate cohort of 88 individuals who participated in CORP. Comparison of the study results found that 14.1% of the CORP participants were rearrested within 6 months of discharge compared to 28.3% of the DMHAS group. This study concluded that younger age and having a co occurring substance use disorder appear to be predictors of recidivism. A distinctly smaller percentage of CORP participants were recidivistic, indicating support for specialized reentry programs. PMID- 22095007 TI - Nonviolent communication training and empathy in male parolees. AB - The purpose of this study was to determine the impact of a behavioral intervention, nonviolent communication (NVC), on the development of empathic coping and communication skills in a sample of male parolees enrolled in substance abuse treatment (SAT; N = 30). At the end of the 8-week intervention, results revealed a significant increase (p = .01) in participants' empathy levels. Findings also revealed the acceptability and utility of NVC training to men on parole. Results suggest that NVC training may (a) be a useful addition to substance abuse treatment programs for parolees, (b) be effective in addressing problematic coping and communication styles resulting from incarceration and criminal behavior, and (c) assist paroled individuals in building and sustaining positive social support networks. PMID- 22095008 TI - Historical impact to drive research in peptic ulcer disease. AB - The story of gastric acid secretion began with early ideas on gastric secretion (Spallanzani and de Reaumur, 17th century) and with first descriptions of food digestion (Dupuytren and Bichat, Beaumont, early 18th century), followed by proof that gastric juice contained acid (Prout, early 18th century). The research continued with first descriptions of gastric glands as the source of gastric acid and its changes upon digestive stimulus (Purkinje and Golgi, mid and late 19th century). The theory of 'nervism' - the neuro-reflex stimulation of gastric secretion by vagal nerve (Pavlov, early 20th century) was contrasted by a histamine-mediated concept of gastric secretion (Popielski and Code, mid 20th century). Thus, gastric acid and pepsin (Schwann, early 19th century) were found to be essential for food digestion and studies also pointed to histamine, being the most potent final common chemostimulator of oxyntic cells. The discoveries in etiopathogenesis of mucosal injury were marked by the famous dictum: 'No acid, no ulcer' ('Ohne saueren Magensaft kein peptisches Geschwur', Schwarz, 1910) that later induced the term of 'mucosal defense' and the notion that the breaking of 'gastric mucosal barrier' represents the initial step in the process of mucosal injury (Davenport, Code and Scholer, mid 20th century). The prostaglandins were shown to influence all major components of gastric mucosal barrier, described with the term 'cytoprotection' (Vane, Robert and Jacobson, 1970s). Beginning in the latter half of 19th century, the studies on gastric bacteriology that followed enabled the discovery of association between Campylobacter (Helicobacter) pylori and peptic ulcers (Warren and Marshall, 1980s) that led to worldwide major interventions in treating peptic ulcer disease. The surgical approach to peptic ulcer had been outlined by resection procedures (Billroth, Pean, Moynihan, late 19 century) and vagotomy, with or without drainage procedures (Jaboulay, Latarjet, Dragstedt, mid 20th century). Antacids, protective agents, anticholinergics, and later gastrin antagonists and prostaglandins were used for decades in the treatment of peptic ulcer, with differing effects. The advent of the concept of H(2)-receptor antagonists (Black, 1970s) and the discovery of acid (proton) pumps in parietal cells (Ganser, Forte and Sachs, late 1970s) paved the way for potent (H(2) antagonists) and profound acid inhibition (proton pump inhibitors) that revolutionized the treatment of acid-related disorders, including peptic ulcer disease. Worldwide, peptic ulcer and its complications remain the cause of significant morbidity, especially in older age groups, representing a major burden for ambulatory and hospital healthcare resources. PMID- 22095009 TI - Etiopathogenetic principles and peptic ulcer disease classification. AB - Ulceration corresponds to tissue loss, breaching the muscularis mucosae. When ulcers develop in the acid-peptic environment of the gastroduodenum, they are traditionally called peptic ulcer (PUD). Ulcers never develop spontaneously in a healthy gastroduodenal mucosa. Ulceration is the ultimate consequence of a disequilibrium between aggressive injurious factors and defensive mucosa protective factors. The dominant aggressors are strong acid and high proteolytic (pepsin) activity in gastric secretions. The dominant defensors are the phospholipid surfactant layer, covering the mucus bicarbonate gel, the mucus bicarbonate layer covering the epithelium, the tight junctional structures between the epithelial cells, restricting proton permeability, and the epithelial trefoil peptides, contributing to healing after injury. Initially, acid-peptic aggression was considered the overwhelming cause of PUD, supported by the pioneering work of Schwartz, launching the dictum 'no acid, no ulcer'. This led to the universal therapy directed against intragastric acidity, also interfering with peptic activity when the pH was >4. The therapeutic sequence went from large doses of antacids to H(2)-receptor antagonists and finally to proton pump inhibitors (PPIs). The longer the intragastric pH was >3, the quicker ulcer healing was seen. Unfortunately, ulcers often recurred after stopping therapy, demanding maintenance therapy to keep the ulcers healed and to prevent the need for surgery (vagotomy, partial gastric resection). Later on, the emphasis gradually shifted to weakening/failing of the defensive factors, raising the vulnerability of the gastroduodenal mucosa to luminal secretions. Leading injurious mechanisms jeopardizing the mucosal integrity are numerous: infections, especially Helicobacter pylori, drug-induced injury, particularly acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs), physicochemical and caustic injury, vascular disorders, interfering with perfusion, etc. Currently the leading cause of PUD is H. pylori infection. Standard triple eradication therapy is losing interest in favor of quadruple therapy (PPI, bismuth, tetracycline, metronidazole). H. pylori-induced PPI is rapidly disappearing in the Western world, in contrast to drug-induced ulcer disease and what is called idiopathic PUD. Partial prophylaxis of ASA/NSAID-induced ulceration is possible with PPI maintenance therapy, but novel ways to strengthen the mucosal defense are urgently awaited. PMID- 22095010 TI - The intriguing relationship of Helicobacter pylori infection and acid secretion in peptic ulcer disease and gastric cancer. AB - Helicobacter pylori infection induces chronic inflammation of the gastric mucosa and thus profoundly affects gastric physiology. In the acute phase of infection, gastric acid secretion is transiently impaired. The morphological damage of the gastric mucosa, changes in gastric hormone release, and disruption of neural pathways all contribute to influence gastric acid secretion in a distinct manner. Changes in gastric acid secretion, whether impaired or increased, are intimately related with the topographic phenotypes of gastritis and the presence of atrophy or absence of corpus atrophy. The interplay of gastritis phenotype and acid secretion are key determinants in disease outcomes. Corpus-predominant gastritis and corpus atrophy are accompanied by hypochlorhydria and carry the highest risk for gastric cancer, whereas antrum-predominant gastritis with little involvement of the corpus-fundic mucosa is associated with hyperchlorhydria and predisposes to duodenal ulcer disease. PMID- 22095011 TI - Acid-NSAID/aspirin interaction in peptic ulcer disease. AB - The presence of gastric acid plays a critical role in the mechanisms of NSAIDs/aspirin-associated gastric and duodenal mucosal injury and ulceration. The role of gastric acid and its relationship to NSAIDs/aspirin in mucosal damage, ulcer and ulcer complications continues to be an important concern because of the increasing worldwide use of NSAIDs and aspirin. Acid suppression continues to be an important prevention strategy for NSAID-associated gastric and duodenal ulcer and ulcer complications. While a coxib or an NSAID and PPI in combination are considered to have comparable safety profiles, the evidence from direct comparisons in high-risk patients is limited, and the cardiovascular safety of coxibs and NSAIDs remains a concern especially in patients with a high risk of cardiovascular disease. An evaluation of individual gastrointestinal and cardiovascular risks and benefits, selection of the most appropriate NSAID and dose for each particular patient should always be emphasized. Twice daily PPI is more appropriate to protect a patient who is taking NSAIDs twice daily. PPI co therapy is still recommended in patients receiving dual antiplatelet treatment, although conflicting results have been reported about adverse drug interactions between PPIs and clopidogrel. PMID- 22095012 TI - Pharmaceutical principles of acid inhibitors: unmet needs. AB - Despite the well-established benefits of currently approved delayed-release proton pump inhibitors (PPIs) in the treatment of acid-related diseases, the unmet needs are still present and although often frustrating, they challenge clinicians. The unmet needs relate to the lack of complete control of acid secretion with oral PPI administration in the management of patients with gastroesophageal symptoms. These substantial groups of patients, who do not respond completely to standard doses of PPIs, are nonresponders, and their lack of response should be considered as PPI failure. Several mechanisms could explain PPI failure: differences in pharmacokinetics, PPI formulation, dosing time and diet, noncompliance, transient lower esophageal sphincter relaxations, esophageal hypersensitivity, and nocturnal acid breakthrough. To increase the quality of life of these patients and avoid multiple medical consultations and unnecessary investigations, we have to go one step forward and use combined therapy or look towards new treatments beyond acid suppression. PMID- 22095013 TI - Long-term acid inhibition: benefits and harms. AB - Proton pump inhibitors (PPIs) are the drugs of choice in the therapy of acid related disorders. PPIs are as a class remarkably safe. Serious adverse events such as acute interstitial nephritis are extremely rare. Some reports in recent years have placed some concern on the long-term use of PPIs. Long-term therapy with PPIs can cause hypochlorhydria, hypergastrinemia and has interactions on hepatic cytochrome P450 enzymes which might increase the risk of infectious complications, nutritional deficiencies and drug-drug interactions. The vast majority of data came from retrospective case-control or cohort studies which are prone to confounders. At the moment we cannot conclude that long-term PPI use causes anemia, osteoporosis and bone fractures, increases the risk for pulmonary or enteric infections, has an effect on GUT mucosa, polyp or tumor formation, or that PPI use increases the risk of cardiovascular events in patients on PPIs and clopidogrel. We need prospective randomized trials to be able to definitely answer the questions raised in epidemiologic studies. Maintenance therapy with PPIs should be started only if strict indications for that therapy are fulfilled. PMID- 22095014 TI - Acid inhibition and the acid rebound effect. AB - Acid secretion from gastric parietal cells is a result of a complex interaction between different stimulatory and inhibitory mediators. One of the most important mediators is gastrin, which stimulates gastric acid secretion from parietal cells mostly indirectly, by the release of histamine from enterochromaffin-like (ECL) cells. Therapy with antisecretory agents leads to hypergastrinemia, mucosal hyperplasia and increased ECL cell mass, which results in increase of gastric acid secretion capacity. This increased secretion capacity has been shown to manifest itself after antisecretory therapy withdrawal as rebound acid hypersecretion (RAH). Various studies have quantified acid hypersecretion after the cessation of therapy with H(2) antagonists and proton-pump inhibitors (PPIs). While most of those studies had small patient numbers, the findings generally demonstrate that RAH after H(2) antagonist therapy is of low magnitude, short duration, and has questionable clinical significance. On the contrary, acid hypersecretion after PPI therapy is more pronounced, lasts longer, and could possibly be the cause of acid-related symptoms. Potential for causing symptoms has recently been confirmed in two randomized placebo-controlled studies, and while we witness the increasing use of PPIs, RAH could become a proven cause of failure to withdraw therapy in a proportion of patients with reflux or dyspeptic symptoms. PMID- 22095015 TI - Acid secretion and gastric surgery. AB - It was long believed that there were major differences in the pathophysiology between the three major categories of peptic ulcers. The unifying feature was that all peptic ulcers occurred in a mucosal compartment exposed to acid-pepsin secretions. All ulcers tended to heal more rapidly when acid secretion was more readily neutralized or inhibited. Decreased local resistance was considered to be present in primarily acute and chronic gastric ulcer. Surgery for peptic ulcer intended to reduce acid secretion, which also resulted in a diminished pepsin enzyme activity. The corresponding reduction could be accomplished either by gastric resection, different vagotomies or a combination of resections and vagotomies. Most of the procedures were basically abandoned at the time of introduction of modern medical therapeutic strategies. For duodenal ulcer and prepyloric ulcer diseases, various vagotomies were generally recommended or combined with antrectomy. Partial gastrectomy or antrectomy with gastroduodenostomy was the standard procedure for treatment of type 1 gastric ulcer. The great caveat associated with surgical procedures for elective treatment of uncomplicated peptic ulcer disease is confined to operative mortality, postoperative morbidity, and late postoperative metabolic sequelae. The only remaining indication today of remedial gastric surgery for peptic ulcer disease is when there is a defined risk for gastric cancer in an unhealed gastric ulcer and very seldom in a case with recurrent or therapy-resistant peripyloric ulcer. PMID- 22095016 TI - Complications of peptic ulcer disease. AB - There are four major complications of peptic ulcer disease (PUD): bleeding, perforation, penetration, and obstruction. Complications can occur in patients with peptic ulcer of any etiology. Despite improvements in the medical management and the lower overall incidence of PUD, there are conflicting data about the incidence of potentially life-threatening ulcer complications. There are important time trends embedded within this stable overall rate of complications: the dramatic decline in the prevalence of Helicobacter pylori (comparing the cohort born from 1900 to 1920 to cohorts born after 1940); an increased use of nonsteroidal anti-inflammatory drugs, and an increased rate of ulcer complications related to such drug use, especially in the elderly. As a result of these trends, ulcer complications are on the rise in older patients but on the decline in younger individuals. Hemorrhage is the most frequent PUD complication and its incidence is increasing in comparison to perforation and stenosis. Therapeutic endoscopy is considered the treatment of choice for bleeding ulcers, reducing the need for emergent surgical procedures to 10-20% of the cases. In recent years, besides the success of angiographic embolization, the containment of massive hemorrhage must also be taken into account. Transcatheter arterial embolization is also an effective and safe treatment in patients with duodenal ulcers re-bleeding after therapeutic endoscopy or surgery. PMID- 22095017 TI - Acid inhibition and peptic ulcer bleeding. AB - Peptic ulcer bleeding is one of the most common emergency situations in medicine. Combined pharmacological and endoscopic therapy together with emerging interventional radiological procedures are successfully treating peptic ulcer disease, reserving surgical procedures for only a small portion of patients unresponsive to 'conventional' therapy. Technological advancement has seen a great improvement in the field of endoscopic treatment in the form of various methods of hemostasis. However, pharmacological therapy with proton pump inhibitors still plays the central role in the peptic ulcer bleeding treatment algorithm. PMID- 22095018 TI - Role of acid suppression in the development and progression of dysplasia in patients with Barrett's esophagus. AB - Barrett's esophagus (BE) usually develops in patients with gastroesophageal reflux disease and therefore it has been suggested that esophageal acid exposure plays an import role in the initiation of BE and its progression towards esophageal adenocarcinoma (EAC). The mechanisms whereby acid exposure causes BE are not completely revealed and the potential role of esophageal acid exposure in carcinogenesis is unclear as well. Since acid exposure is thought to play an important role in the progression of BE, therapies aimed at preventing the development of EAC have primarily focused on pharmacological and surgical acid suppression. In clinical practice, acid suppression is effective in relieving reflux symptoms and decreases esophageal acid exposure in most patients. However, in some individuals, pathological acid exposure persists and these patients continue to be at risk for developing dysplasia or EAC. To date, published trials suggest that acid suppression is able to prevent the development and progression of dysplasia in patients with BE, but definite and compelling proof is still lacking. This article reviews the mechanisms of acid-induced carcinogenesis in BE and the role of acid suppression in the prevention of neoplastic progression. PMID- 22095019 TI - No acid, no ulcer: Dragutin (Carl) Schwarz (1868-1917), the man ahead of his time. AB - Dragutin (Carl) Schwarz (1868-1917) was born in VaraZdin (part of the Austro Hungarian Monarchy then, northwestern part of Croatia today). As many Croats of the period he enrolled in the Vienna School of Medicine and graduated in 1891. After spending some time in a few clinics of the Monarchy, he returned to his homeland in 1895. Named the primary physician of the surgical department of Charity Brothers' Hospital in Zagreb, he motivated lively activities there and became the prominent member of the medical community. Apart from his impressive surgical work, Carl Schwarz is primarily remembered for his dictum 'No acid, no ulcer' (1910) which was proven to be true in the decades that followed. This short editorial aims at recalling those visionary observations ever inviting and challenging further investigations. PMID- 22095020 TI - Hypertrophic osteoarthropathy in a child due to thoracic Hodgkin's disease. PMID- 22095021 TI - [The effects of multimodal intervention for the primary prevention of cardiovascular diseases on depression, anxiety, and Type-D pattern: initial results of the randomized controlled PreFord trial]. AB - Depression, anxiety, and Type-D pattern are associated with the earlier development and faster progression of cardiovascular disease (CVD). The aim of the randomized controlled PreFord trial was to improve multiple biological and psychosocial risk factors in the primary prevention of CVD. A total of 447 women and men with an ESC risk score >5% were randomly assigned to either multimodal or routine care groups. Somatic and psychosocial variables (HADS, DS-14) were assessed before and after the intervention, and annually for 2 years thereafter. The intervention showed no significant effects on the symptoms of depression, anxiety, and type D personality, either in the whole sample or in those with elevated scores at baseline. Thus, our study did not provide evidence that symptoms of depression, anxiety, or Type D personality can be effectively treated by multimodal behavioral interventions for the primary prevention of CVD. PMID- 22095022 TI - [Long-term echocardiographic and clinical follow-up after mitral valve surgery in patients with extensive calcified mitral annulus]. AB - OBJECTIVE: The aim of this study is the analysis of long-term results in patients with hemodynamically significant mitral valve disease due to extensive calcified mitral annulus who underwent decalcification and patch reconstruction. PATIENTS AND METHODS: Between 1996 and 2008 a total of 109 patients underwent surgery in the presence of extensive calcification, severe mitral insufficiency and mitral stenosis. The mean age of patients (65 women, 44 men) was 66.4+/-13.8 years. Mitral valve repair was performed in 53 patients (49%), while the remaining 56 patients (51%) received a mitral valve replacement. In all, 64 patients (59%) required concomitant surgery. The mean follow-up time was 96+/-48 months. RESULTS: Inpatient and late mortality rates were 8.3% (nine patients) and 25.6% (28 patients), respectively. The actuarial survival rates at 5, 8 and 12 years were 88.1%, 76.2% and 66.1%. Echocardiographic follow-up demonstrated mitral insufficiency III in four patients (6%). No patients had mitral insufficiency IV. We observed a significant reduction in left atrium diameter, LVEDD as well as mean transvalvular gradient. Freedom from reoperation at 5 and 8 years was 96.4% and 91.8%, respectively. We found systemic hypertension, diabetes mellitus, age above 65 years, concomitant aortic valve replacement, concomitant procedures, chronic renal insufficiency and cardiac decompensation in the medical history as predictors for significantly increased early or late mortality. CONCLUSION: The long-term results strongly suggest that en bloc decalcification and patch reconstruction of the mitral annulus can be safely undertaken in high-risk patients. PMID- 22095023 TI - A dedicated cardioversion unit for the treatment of atrial fibrillation. Reducing costs by optimizing processes. AB - BACKGROUND: Atrial fibrillation (AF) is the most frequent arrhythmia seen in man. Many patients are admitted to the hospital to undergo transesophageal echocardiography (TEE) for thrombus exclusion and subsequent electrical cardioversion (ECV) under deep sedation to restore sinus rhythm. The present study investigated prospectively how workflow optimization can contribute to reducing time and costs in AF patients scheduled for ECV in an outpatient setting. METHODS: A cardioversion unit (CU) was established and equipped to perform all ECV-associated procedures. Between November 2007 and January 2009, ECV was performed in 115 patients in an outpatient setting. Three different settings were tested for ECV: (1) usual care (n = 19): preparation/follow-up in the outpatient clinic, blood testing in the central hospital laboratory (CHL), TEE in the echocardiography laboratory, and ECV in the intensive care unit; (2) optimized process 1 (n = 41): preparation/follow-up, TEE + ECV during one sedation in the CU, blood testing in the CHL; (3) optimized process 2 (n = 55): preparation/follow-up, TEE + ECV and point of care (POC) blood testing in the CU. All procedure-related costs were listed and classified according to material, human resources, and infrastructure. RESULTS: From setting 1 to 3, there was a significant decrease in procedural time from 480 +/- 105 min to 205 +/- 85 min (p < 0.001). Likewise, ECV-associated costs could be reduced from 683 +/- 104 to 299 +/- 63 (p < 0.001). CONCLUSION: Establishing a CU for AF enables a more than 50% reduction in procedural time and costs. A combination of TEE and ECV in one sedation and POC testing in the CU were the major contributors to this time and cost reduction. PMID- 22095024 TI - Interaction of the main components from the traditional Chinese drug pair Chaihu Shaoyao based on rat intestinal absorption. AB - The Chaihu-Shaoyao drug pair (Bupleuri Radix and Paeoniae Radix Alba) which is a traditional Chinese drug pair, has been widely used for anti-inflammatory purposes. Saikosaponin a (SSA), saikosaponin d (SSD) and paeoniflorin are identified as the main components in the pair. The present study focused on the interaction of the main components based on investigating their intestinal absorption using a four-site perfused rat intestinal model in order to clarify the mechanism of the compatibility of Chaihu-Shaoyao. The concentrations of SSA, SSD and paeoniflorin in the intestinal perfusate were determined by LC/MS or UPLC (Ultra Performance Liquid Chromatography) methods, followed by P*(eff) (effective permeability) and 10% ABS (the percent absorption of 10 cm of intestine) calculations. The results showed that all of the three main components displayed very low permeabilities (P*(eff) < 0.4), which implied their poor absorption in the rat intestine. The absorption levels of SSA and SSD were similar in intestine and higher in ileum than those in other intestinal regions in the decreasing order: colon, jejunum and duodenum. However, there is no significant difference in the absorption of paeoniflorin in the four segments (P < 0.05). The P*(eff) values of paeoniflorin exhibited an almost 2.11-fold or 1.90-fold increase in ileum when it was co-administrated with SSA and SSD, as well as 2.42-, 2.18-fold increase in colon, respectively, whereas the absorptions of SSA and SSD were not influenced by paeoniflorin. In conclusion, SSA and SSD could promote the absorption of paeoniflorin. To some extent this might explain the nature of the compatibility mechanisms of composite formulae in TCMs. PMID- 22095025 TI - Structure and properties of nano-confined poly(3-hexylthiophene) in nano array/polymer hybrid ordered-bulk heterojunction solar cells. AB - The ordered-bulk heterojunction (BHJ) photovoltaic device comprising a semiconducting donor polymer incorporated into pristine/unmodified vertically aligned arrays of metal oxide acceptor nanotubes/nanorods is widely perceived as being structurally ideal for energy conversion but the power conversion efficiencies of such devices remain relatively low (in the order of eta = 0.6%) when compared with bilayer or non-ordered bulk heterojunction systems. We explain the incongruity by investigating the morphology and microstructure of regio regular poly(3-hexyl thiophene) (P3HT) infiltrated and confined within the cavities of TiO(2) nanotube arrays. A series of TiO(2) nanotube arrays with different nanotube diameters and inter-nanotube spacings are fabricated by the liquid-phase atomic layer deposition (LALD) technique, and P3HT is infiltrated into the array cavities via a vacuum-annealing technique. X-Ray diffraction studies reveal that the P3HT chains in both nano-confined and non-confined (i.e. planar film) environments are well-aligned and oriented edge-on with respect to the underlying substrate. Up to 2.5-fold improvement in the incident-photon-to converted-electron efficiency (IPCE) is observed in ordered-BHJ structures over benchmark planar devices which we attribute to the increase in interfacial area resulting from the use of the nanostructures. However, the large effective surface area conferred by the nano-arrays (up to 9.5 times that of the planar system) suggests that much higher efficiencies could be harnessed. Our study shows that the morphology and orientation of the infiltrated polymer play a critical role in the charge transport of the device, and suggests that better understanding and control of polymer morphology under nano-confinement in the nano-array will be the key to fully reaping the promised benefit of ordered-BHJ devices. PMID- 22095026 TI - Thiacalix[4]arene based fluorescent probe for sensing and imaging of Fe3+ ions. AB - A thiacalix[4]arene based fluorescent chemosensor 3 in the cone conformation has been synthesized and its recognition behaviour is evaluated toward various metal ions in mixed aqueous media. The chemosensor 3 showed high selectivity towards Fe(3+) ions by fluorescence quenching of excimer emission. Further, evaluation of the 3.Fe(3+) complex prepared in situ demonstrated great promise for the detection of the Fe(3+) ion in the presence of amino acids, blood serum and bovine serum albumin (BSA) solution. The compound 3 has suitable permeability into the PC3 cells and can be utilized as a Fe(3+) selective sensor in living cells (PC3 cells). PMID- 22095028 TI - [Aspects of drug safety in the German code of social security]. PMID- 22095027 TI - [New approaches to the monitoring of hospital hygiene: assessment of hygiene skills of staff members by structured interviews and observation]. AB - INTRODUCTION: Increasing demands on hygiene in hospitals require improved methods of systematic monitoring by the Public Health Service. METHODS: The hygiene skills of at least 20% of the hospital physicians and nurses were evaluated by structured interviews and observation. The results were presented to the hospitals. RESULTS: In total, 184 persons were reviewed in 5 hospitals. On average, 7 out of 10 questions on hygiene knowledge were answered correctly, 74% of the persons asked demonstrated proper hand hygiene and 66% of them were not wearing any jewellery on their hands. There were no significant differences between physicians and nurses. The slight differences between the 5 hospitals were transferred into a ranking. CONCLUSIONS: The application of the method provides additional information on hygiene in hospitals and allows a comparison of the hygiene skills of their staff members. The results form the basis for a dialogue between hospital and Public Health Service. PMID- 22095030 TI - Regulation of p53 by ING family members in suppression of tumor initiation and progression. AB - The INhibitor of Growth (ING) family is an evolutionarily conserved set of proteins, implicated in suppression of initiation and progression of cancers in various tissues. They promote cell cycle arrest, cellular senescence and apoptosis, participate in stress responses, regulate DNA replication and DNA damage responses, and inhibit cancer cell migration, invasion, and angiogenesis of the tumors. At the molecular level, ING proteins are believed to participate in chromatin remodeling and transcriptional regulation of their target genes. However, the best known function of ING proteins is their cooperation with p53 tumor suppressor protein in tumor suppression. All major isoforms of ING family members can promote the transactivition of p53 and the majority of them are shown to directly interact with p53. In addition, ING proteins are thought to interact with and modulate the function of auxiliary members of p53 pathway, such as MDM2, ARF , p300, and p21, indicating their widespread involvement in the regulation and function of this prominent tumor suppressor pathway. It seems that p53 pathway is the main mechanism by which ING proteins exert their functions. Nevertheless, regulation of other pathways which are not relevant to p53, yet important for tumorigenesis such as TGF-beta and NF-kappaB, by ING proteins is also observed. This review summarizes the current understanding of the mutual interactions and cooperation between different members of ING family with p53 pathway and implications of this cooperation in the suppression of cancer initiation and progression. PMID- 22095029 TI - Newcastle disease virus induces apoptosis in cisplatin-resistant human lung adenocarcinoma A549 cells in vitro and in vivo. AB - Cisplatin (DDP) is widely used in lung cancer chemotherapy. However, cisplatin resistance represents a major obstacle in effective clinical treatment. This study aims to investigate whether Newcastle disease virus (NDV) exhibits an oncolytic effect on cisplatin-resistant A549 lung cancer cells. We found that NDV induced A549/DDP cell apoptosis via the caspase pathway, particularly involving caspase-9, while the mitogen-activated protein kinase (MAPK) and Akt pathways also contributed to apoptotic induction. Furthermore, NDV displayed oncolytic effects in a mouse A549/DDP lung cancer model. Collectively, our data indicate that NDV could overcome the cisplatin resistance in lung cancer cells in vitro and in vivo. PMID- 22095031 TI - Molecular characterization of intercellular adhesion gene in Staphylococcus aureus isolated from bovine mastitic milk. AB - Biofilm formation in Staphylococcus aureus is considered an important virulence factor in bovine mastitis. Intercellular adhesion gene A (icaA) is a significant genetic determinant that contributes in biofilm formation. The aim of the present study was to determine the presence of the icaA gene in S. aureus isolated from bovine mastitis from seven states of India. A total of 88 out of 150 Staphylococcus aureus strains were found to be positive for biofilm marker icaA gene by PCR. The icaA gene was confirmed by dot blot hybridization in 41 of 150 S. aureus strains tested. Results obtained with dot blot hybridization were comparable to those obtained with PCR. Partial sequences of the icaA gene of the two S. aureus isolates showed deletion of some bases in different positions that might reduce/stop transcription leading to no biofilm formation. PCR was found to be a rapid test but dot blot hybridization was more accurate than PCR for detection of icaA genes. This study showed that detection of biofilm marker the icaA gene in S. aureus would allow the detection of virulence factors present in mastitis and early application of corrective measures. PMID- 22095032 TI - Potential use of coronary artery calcium progression to guide the management of patients at risk for coronary artery disease events. AB - OPINION STATEMENT: Subclinical coronary artery disease (CAD) is widespread and under-diagnosed. Preventive efforts are required to reduce the burden of this disease and its complications. Imaging of coronary artery calcium (CAC) with cardiac computed tomography is highly specific for the diagnosis of subclinical CAD and can also facilitate treatment decisions in preventive cardiology. Indeed, CAC testing has been recommended by the American Heart Association for asymptomatic patients at intermediate risk for future cardiac events (as defined by clinical risk factors) to refine existing risk estimates. However, the optimal follow-up of those patients who have already undergone CAC testing remains unclear, particularly with regards to repeat CAC testing. The existing literature points to two major considerations for the use of CAC progression in the management of subclinical CAD. On one hand, CAC progression has been used as a surrogate marker to test the efficacy of cardiac preventive medications in halting or regressing CAD. To date, study results have been mostly disappointing and CAC progression appears resistant to medications such as statins. On the other hand, however, CAC progression has potential as a clinical indicator of underlying CAD activity. This may facilitate optimization or up-titration of preventive medications by using CAC progression as a marker of subclinical disease activity. We believe that the data, thus far, argues against the use of a CAC progression as a clinical surrogate marker of preventive therapy efficacy. Further studies with non-statin medications and with concomitant outcome data are needed. However, CAC progression has potential for monitoring subclinical CAD in some patients and may facilitate treatment decisions. In this review we will provide recommendations for repeat CAC testing and discuss when repeat CAC testing may be helpful to assess coronary artery disease progression. PMID- 22095033 TI - Emerging perspectives on transforming the healthcare system: developing a research agenda. PMID- 22095034 TI - Emerging perspectives on transforming the healthcare system: redesign strategies and a call for needed research. AB - BACKGROUND: U.S. healthcare requires major redesign of its delivery systems, finances, and incentives. Healthcare operations, leadership, and payors are increasingly recognizing the need for community-business-research partnerships to transform healthcare. New models of continuous learning, research, and development should help focus and sustain redesign efforts. PURPOSE: This study summarizes suggested strategies for transformational change in healthcare and identifies needed areas for research to inform, spread, and sustain transformational change. METHODS: We developed these recommendations based on a series of review papers, invited expert discussion, and a subsequent review in the context of a health system transformation research conference (The Regenstrief Biennial Research Conference). The multidisciplinary audience included health systems researchers, clinicians, informaticians, social and engineering scientists, and operational and business leaders. FINDINGS: Conference participants and literature reviews identified key strategies for system redesign with the following themes: using the framework of complex adaptive systems; fostering organizational redesign; developing appropriate performance measures and incentives; creating continuous learning organizations; and integrating health information, technology, and communication into practice. Sustained investment in research and development in these areas is crucial. CONCLUSIONS: Multiple issues influence the likelihood that healthcare leaders will make transformational changes in their healthcare systems. Healthcare leaders, clinicians, researchers, journals, and academic institutions, in partnership with payors, government and multiple other stakeholders, should apply the recommendations relevant to their own setting to redesign healthcare delivery, improve cognitive support, and sustain transformation. Fostering further research investments in these areas will increase the impact of transformation on the health and healthcare of the public. PMID- 22095035 TI - Quality improvement implementation and disparities: the case of the health disparities collaboratives. AB - BACKGROUND: The Health Disparities Collaboratives (HDCs), a quality improvement (QI) collaborative incorporating rapid QI, a chronic care model, and learning sessions, have been implemented in over 900 community health centers across the country. OBJECTIVES: To determine the HDC's effect on clinical processes and outcomes, their financial impact, and factors important for successful implementation. RESEARCH DESIGN: Systematic review of the literature. RESULTS: The HDCs improve clinical processes of care over short-term period of 1 to 2 years, and clinical processes and outcomes over longer period of 2 to 4 years. Most participants perceive that the HDCs are successful and worth the effort. Analysis of the Diabetes Collaborative reveals that it is societally cost effective, with an incremental cost-effectiveness ratio of $33,386 per quality adjusted life year, but that consistent revenue streams for the initiative do not exist. Common barriers to improvement include lack of resources, time, and staff burnout. Highest ranked priorities for more funding are money for direct patient services, data entry, and staff time for QI. Other common requests for more assistance are help with patient self-management, information systems, and getting providers to follow guidelines. Relatively low-cost ways to increase staff morale and prevent burnout include personal recognition, skills development opportunities, and fair distribution of work. CONCLUSIONS: The HDCs have successfully improved quality of care, and the Diabetes Collaborative is societally cost-effective, but policy reforms are necessary to create a sustainable business case for these health centers that serve many uninsured and underinsured populations. PMID- 22095036 TI - Independent replication of STAT3 association with multiple sclerosis risk in a large German case-control sample. AB - Recent genome-wide association studies have implicated the "signal transducer and activator of transcription 3" gene (STAT3) as a putative new multiple sclerosis (MS) susceptibility locus. However, independent validation studies are sparse. Therefore, we performed a genetic association study of two STAT3 polymorphisms (rs744166 and rs2293152) in a large and independent German case-control sample of 5,904 subjects. We observed a nominally significant, albeit weak association between rs744166 and MS susceptibility (odds ratio = 1.09, P = 0.012) in our sample. This study supports the association between STAT3 and an increase in MS risk. Taking into account the functional role of STAT3, our results favour an involvement of T(h)17 lymphocytes in MS. PMID- 22095037 TI - Identification and role of muscarinic receptor subtypes expressed in rat adrenal medullary cells. AB - The muscarinic receptor is known to be involved in the acetylcholine (ACh) induced secretion of catecholamines in the adrenal medullary (AM) cells of various mammals. The muscarinic receptor subtype involved and its physiological role, however, have not been elucidated yet. Thus, we investigated these issues in acutely isolated rat AM cells and perfused rat adrenal medulla. The RT-PCR analysis revealed the presence of M(2), M(3), M(4), and M(5) mRNAs. Immunocytochemistry with specific antibodies showed that M(5)-like immunoreactivities (IRs) were detected at half the cell membrane area, which was much larger than that with M(3)- or M(4)-like IRs. Muscarine produced inward currents in a dose-dependent manner. Pilocarpine, McN-A-343, and oxotremorine were less efficient than muscarine; and RS-86, which has no action on the M(5) receptor, produced no current. Electrical stimulation of nerve fibers produced a frequency-dependent increase in the Ca(2+) signal in perfused adrenal medullae. Muscarinic receptors were found to be involved in neuronal transmission in AM cells in the presence of a cholinesterase inhibitor, which suppresses ACh degradation. We concluded that the M(5) receptor is the major muscarinic receptor subtype in rat AM cells and may be involved in neuronal transmission under conditions where ACh spills over the synapse. PMID- 22095038 TI - Determinants of blood uric acid levels in a dyslipidemic Arab population. AB - OBJECTIVES: The objective of this study was to explore the relationships between circulating uric acid and lipid levels and components of the metabolic syndrome (MetS) in Arab dyslipidemic patients, a group already at high coronary artery disease risk. SUBJECTS AND METHODS: The medical records of 1,229 subjects (632 men, 597 women) referred for treatment of dyslipidemia and followed up for at least 12 months were reviewed. Serum levels of uric acid and lipids (total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein) and other variables in the National Cholesterol Education Program ATP III criteria definition of MetS were assessed at initial presentation and every 4- 6 months, under specific lipid-lowering treatment (statins and/or fibrates), in each of the subjects. Their respective associations were explored by appropriate logistic regression techniques with control for confounding risk factors, including age, gender and body mass index. RESULTS: 306 subjects (24.9%) of the study population were hyperuricemic; they were more likely to be men, obese and diabetic. Also the serum uric acid level (mean +/- SD) was greater in men with MetS compared with men without (377.0 +/- 98.0 vs. 361.6 +/- 83.1 MUmol/l, p < 0.05), an observation not reproduced in women. Uric acid levels had significant associations with the presence of fasting hyperglycemia, hypertension and large waist circumference (WC) in men, but only with large WC in women. With statin treatment, uric acid levels decreased by 10% within 1 year of treatment; with fibrates, uric acid levels remained unchanged or slightly increased. CONCLUSION: The data showed that hyperuricemia is common in dyslipidemic patients in Kuwait, where its important determinants are male sex, obesity, diabetes and statin treatment. PMID- 22095039 TI - The effect of biofilm permeability on bio-clogging of porous media. AB - A 3D Biofilm model, appropriate for complex porous media support structures, is successfully modified such that non-zero permeability of biofilms structures is enabled. A systematic study is then conducted into the influence of biofilm permeability on overall biomass growth rate. This reveals a significant influence at large biofilm concentrations; even when the permeability of the biomass is 1.25% of that of the free pore space, biomass accumulation increased by a factor of ~3 over 40 h. The effect is shown to be retained when allowing for biomass detachment or erosion as a consequence of adjacent velocity shear. We conclude that biofilm permeability should be included in biofilm models and that further experimental work is required to better describe the link between biofilm permeability and local microstructure. PMID- 22095040 TI - Early and presenting symptoms of dementia with lewy bodies. AB - BACKGROUND/AIMS: To explore the presenting and early symptoms of dementia with Lewy bodies (DLB). METHOD: Patients with mild dementia fulfilling diagnostic criteria for DLB (n = 61) and Alzheimer's disease (AD) (n = 109) were recruited from outpatient dementia clinics in western Norway. At diagnosis, caregivers were asked which symptom had been the presenting symptom of dementia. RESULTS: Caregivers reported that memory impairment was the most common presenting symptom in DLB (57%), followed by visual hallucinations (44%), depression (34%), problem solving difficulties (33%), gait problems (28%), and tremor/stiffness (25%). In contrast, 99% of AD carers reported impaired memory as a presenting symptom, whereas visual hallucinations were a presenting symptom in 3% of the AD cases. CONCLUSION: DLB should be suspected in predementia cases with visual hallucinations. PMID- 22095041 TI - The pulvinar sign in Fabry patients: the first report in female patients. PMID- 22095042 TI - Low depressive symptoms in acute spinal cord injury compared to other neurological disorders. AB - The aim of the study was to reveal the incidence and time course of depressive symptoms following acute spinal cord injury (SCI) in relation to clinical outcomes for comparison to other neurological disorders with severe impairment. In patients with acute traumatic SCI (n = 130), combined follow up assessments of neurological and functional outcomes, pain and patient-rated affective factors (e.g. mood, anxiety) were prospectively (1, 3, 6, 12 months after injury) collected during rehabilitation and follow up in out-patient clinics. We related these to the severity of depressive symptoms (no, mild, moderate and severe) based on the Beck Depression Inventory (BDI) scores. The mean 65% of patients showed no depressive symptoms and 30% mild depressive symptoms, while less than 5% presented moderate to severe depressive symptoms. The group findings and symptoms in individual patients remained stable over 1 year though patients revealed significant clinical recovery. Although two-thirds of the patients experienced pain, BDI scores were not related to pain intensity. BDI mean scores were only slightly higher than in control populations, but rather low compared to patients with other neurological disorders (e.g. stroke and multiple sclerosis) that are also associated with severe functional impairment. The prevalence of depressive symptoms following acute SCI is rather low and remains stable within the first year after injury despite the severe neurological impairment and loss of independency. In comparison to other neurological disorders that also involve brain function SCI patients seem to be less challenged by depressive symptoms that constitute additional burdens to respond to the severe functional impairments. PMID- 22095043 TI - The SigB sigma factor regulates multiple salt acclimation responses of the cyanobacterium Synechocystis sp. PCC 6803. AB - Changing of principal sigma factor in RNA polymerase holoenzyme to a group 2 sigma factor redirects transcription when cyanobacteria acclimate to suboptimal environmental conditions. The group 2 sigma factor SigB was found to be important for the growth of the cyanobacterium Synechocystis sp. PCC 6803 in high-salt (0.7 m NaCl) stress but not in mild heat stress at 43 degrees C although the expression of the sigB gene was similarly highly, but only transiently up regulated at both conditions. The SigB factor was found to regulate many salt acclimation processes. The amount of glucosylglycerol-phosphate synthase, a key enzyme in the production of the compatible solute glucosylglycerol, was lower in the inactivation strain DeltasigB than in the control strain. Addition of the compatible solute trehalose almost completely restored the growth of the DeltasigB strain at 0.7 m NaCl. High-salt conditions lowered the chlorophyll and phycobilin contents of the cells while protective carotenoid pigments, especially zeaxanthin and myxoxanthophyll, were up-regulated in the control strain. These carotenoids were up-regulated in the DeltasigCDE strain (SigB is the only functional group 2 sigma factor) and down-regulated in the DeltasigB strain under standard conditions. In addition, the HspA heat shock protein was less abundant and more abundant in the DeltasigB and DeltasigCDE strains, respectively, than in the control strain in high-salt conditions. Some cellular responses are common to heat and salt stresses, but pretreatment with mild heat did not protect cells against salt shock although protection against heat shock was evident. PMID- 22095045 TI - Chromosome organization and dynamics during interphase, mitosis, and meiosis in plants. PMID- 22095044 TI - CO(2)-cAMP-responsive cis-elements targeted by a transcription factor with CREB/ATF-like basic zipper domain in the marine diatom Phaeodactylum tricornutum. AB - Expression controls of the carbon acquisition system in marine diatoms in response to environmental factors are an essential issue to understand the changes in marine primary productivity. A pyrenoidal beta-carbonic anhydrase, PtCA1, is one of the most important candidates to investigate the control mechanisms of the CO(2) acquisition system in the marine diatom Phaeodactylum tricornutum. A detailed functional assay was carried out on the putative core regulatory region of the ptca1 promoter using a beta-glucuronidase reporter in P. tricornutum cells under changing CO(2) conditions. A set of loss-of-function assays led to the identification of three CO(2)-responsive elements, TGACGT, ACGTCA, and TGACGC, at a region -86 to -42 relative to the transcription start site. Treatment with a cyclic (c)AMP analog, dibutyryl cAMP, revealed these three elements to be under the control of cAMP; thus, we designated them, from 5' to 3', as CO(2)-cAMP-Responsive Element1 (CCRE1), CCRE2, and CCRE3. Because the sequence TGACGT is known to be a typical target of human Activating Transcription Factor6 (ATF6), we searched for genes containing a basic zipper (bZIP) region homologous to that of ATF6 in the genome of P. tricornutum. Gel-shift assays using CCRE pentamers as labeled probes showed that at least one candidate of bZIP proteins, PtbZIP11, bound specifically to CCREs. A series of gain-of-function assays with CCREs fused to a minimal promoter strongly suggested that the alternative combination of CCRE1/2 or CCRE2/3 at proper distances from the minimal promoter is required as a potential target of PtbZIP11 for an effective CO(2) response of the ptca1 gene. PMID- 22095046 TI - Drought and salt stress tolerance of an Arabidopsis glutathione S-transferase U17 knockout mutant are attributed to the combined effect of glutathione and abscisic acid. AB - Although glutathione S-transferases (GSTs) are thought to play major roles in oxidative stress metabolism, little is known about the regulatory functions of GSTs. We have reported that Arabidopsis (Arabidopsis thaliana) GLUTATHIONE S TRANSFERASE U17 (AtGSTU17; At1g10370) participates in light signaling and might modulate various aspects of development by affecting glutathione (GSH) pools via a coordinated regulation with phytochrome A. Here, we provide further evidence to support a negative role of AtGSTU17 in drought and salt stress tolerance. When AtGSTU17 was mutated, plants were more tolerant to drought and salt stresses compared with wild-type plants. In addition, atgstu17 accumulated higher levels of GSH and abscisic acid (ABA) and exhibited hyposensitivity to ABA during seed germination, smaller stomatal apertures, a lower transpiration rate, better development of primary and lateral root systems, and longer vegetative growth. To explore how atgstu17 accumulated higher ABA content, we grew wild-type plants in the solution containing GSH and found that they accumulated ABA to a higher extent than plants grown in the absence of GSH, and they also exhibited the atgstu17 phenotypes. Wild-type plants treated with GSH also demonstrated more tolerance to drought and salt stresses. Furthermore, the effect of GSH on root patterning and drought tolerance was confirmed by growing the atgstu17 in solution containing l-buthionine-(S,R)-sulfoximine, a specific inhibitor of GSH biosynthesis. In conclusion, the atgstu17 phenotype can be explained by the combined effect of GSH and ABA. We propose a role of AtGSTU17 in adaptive responses to drought and salt stresses by functioning as a negative component of stress-mediated signal transduction pathways. PMID- 22095047 TI - Arabidopsis RGLG2, functioning as a RING E3 ligase, interacts with AtERF53 and negatively regulates the plant drought stress response. AB - Transcriptional activities of plants play important roles in responses to environmental stresses. ETHYLENE RESPONSE FACTOR53 (AtERF53) is a drought-induced transcription factor that belongs to the AP2/ERF superfamily and has a highly conserved AP2 domain. It can regulate drought-responsive gene expression by binding to the GCC box and/or the dehydration-responsive element in the promoter of downstream genes. Overexpression of AtERF53 driven by the cauliflower mosaic virus 35S promoter resulted in an unstable drought-tolerant phenotype in T2 transgenic Arabidopsis (Arabidopsis thaliana) plants. Using a yeast two-hybrid screen, we identified a RING domain ubiquitin E3 ligase, RGLG2, which interacts with AtERF53 in the nucleus. The copine domain of RGLG2 exhibited the strongest interacting activity. We also demonstrated that RGLG2 could move from the plasma membrane to the nucleus under stress treatment. Using an in vitro ubiquitination assay, RGLG2 and its closest sequelog, RGLG1, were shown to have E3 ligase activity and mediated AtERF53 ubiquitination for proteasome degradation. The rglg1rglg2 double mutant but not the rglg2 or rglg1 single mutant exhibited a drought-tolerant phenotype when compared with wild-type plants. AtERF53-green fluorescent proteins expressed in the rglg1rglg2 double mutants were stable. The 35S:AtERF53-green fluorescent protein/rglg1rglg2 showed enhanced AtERF53 regulated gene expression and had greater tolerance to drought stress than the rglg1rglg2 double mutant. In conclusion, RGLG2 negatively regulates the drought stress response by mediating AtERF53 transcriptional activity in Arabidopsis. PMID- 22095048 TI - [Treatment of non-small cell lung cancer]. AB - Within recent years, the treatment of non-small cell lung cancer has become increasingly heterogeneous and complex. New cytotoxic agents and drugs against molecular targets have been developed. Moreover, new indications for therapy such as maintenance therapy have been explored. In addition, by assessing defined molecular markers, it is possible to identify patients who may likely respond to a given treatment. This approach will continue in the future; thus, it will be possible to characterize patient into subgroups based on molecular, histological, or clinical markers. This review will summarize the current state of the art in the treatment of non-small cell lung cancer. PMID- 22095049 TI - [Treatment of pulmonary fibrosis. New substances and new interventions]. AB - Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor prognosis. The IFIGENIA trial showed that antioxidative therapy with N acetylcysteine versus placebo for patients under treatment with prednisone plus azathioprine significantly slowed the deterioration of pulmonary function after 12 months. A number of other drugs have recently been evaluated in large multicenter placebo-controlled trials. Etanercept, interferon-gamma, bosentan, ambrisentan, imatinib, and sildenafil did not show efficacy. The antifibrotic active ingredient pirfenidone is the first drug approved for the treatment of adult patients with mild to moderate idiopathic pulmonary fibrosis in the European Union. Approval was based on the results of 4 randomized, placebo controlled clinical trials including more than 1,100 patients. Pirfenidone slowed the decline in lung function and reduced the risk of disease progression. Side effects include gastrointestinal discomfort, skin reactions, including photosensitivity, and rarely increased liver enzymes. PMID- 22095050 TI - Predictive value of dopamine transporter SPECT imaging with [123I]PE2I in patients with subtle parkinsonian symptoms. AB - PURPOSE: To examine the diagnostic sensitivity and specificity of dopamine transporter SPECT imaging with a highly dopamine transporter selective radioligand. The study included consecutively enrolled, drug-naive patients with an average short history of parkinsonian motor symptoms, referred for diagnostic scanning. METHODS: The study group comprised 288 patients naive to antiparkinson treatment who were enrolled as they were admitted for a diagnostic SPECT scan with the radioligand [(123)I]-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3beta-(4 methylphenyl)nortropane ((123)I-PE2I). After the diagnostic scanning, patients were followed clinically with an average follow-up of 19.7 +/- 12.5 months. RESULTS: A diagnosis could be clinically settled in 189 patients and among these patients, a dopamine transporter scan had a sensitivity of 88% and a specificity of 91% for discrimination between patients with and without striatal neurodegeneration. In cognitively impaired patients (Mini Mental State Examination <27) the specificity was 75% and the sensitivity 95%. A striatal anterior-posterior ratio (APR) of >2 differentiated between idiopathic Parkinson's disease and atypical parkinsonian syndromes with a specificity of 84% and a sensitivity of 63%. CONCLUSION: In drug-naive patients with subtle clinical parkinsonian motor symptoms, dopamine transporter scan using (123)I-PE21 has a high sensitivity and specificity in distinguishing between patients with and without striatal neurodegeneration. The specificity is lower in patients who are also cognitively impaired. Calculation of the striatal APR can assist in differentiating between idiopathic Parkinson's disease and atypical parkinsonian syndromes. PMID- 22095051 TI - Adsorption and properties of aromatic amino acids on single-walled carbon nanotubes. AB - We investigated the adsorption of three aromatic amino acids-phenylalanine, tyrosine, and tryptophan-on the sidewalls of a number of representative single walled carbon nanotubes (SWNTs) using density-functional tight-binding calculations, complemented by an empirical dispersion correction. The armchair (n, n) SWNTs (n = 3-12) and zigzag (n, 0) SWNTs (n = 4-12) were thoroughly examined. We found that the most stable amino acid/SWNT complexes for different SWNTs have similar local structures, and that the distance between the amino acid and SWNT is about 3 A. Owing to the pi-pi and H-pi stacking interactions, the benzene and indole rings are not exactly parallel to the SWNTs but instead lie at a small angle. We also investigated the diameter and chirality dependences of binding energies and found that SWNT (5, 0) has an especially large binding energy that can be used for SWNT identification or selection. PMID- 22095052 TI - Bacterial delivery of large intact genomic-DNA-containing BACs into mammalian cells. AB - Efficient delivery of large intact vectors into mammalian cells remains problematical. Here we evaluate delivery by bacterial invasion of two large BACs of more than 150 kb in size into various cells. First, we determined the effect of several drugs on bacterial delivery of a small plasmid into different cell lines. Most drugs tested resulted in a marginal increase of the overall efficiency of delivery in only some cell lines, except the lysosomotropic drug chloroquine, which was found to increase the efficiency of delivery by 6-fold in B16F10 cells. Bacterial invasion was found to be significantly advantageous compared with lipofection in delivering large intact BACs into mouse cells, resulting in 100% of clones containing intact DNA. Furthermore, evaluation of expression of the human hypoxanthine phosphoribosyltransferase (HPRT) gene from its genomic locus, which was present in one of the BACs, showed that single copy integrations of the HPRT-containing BAC had occurred in mouse B16F10 cells and that expression of HPRT from each human copy was 0.33 times as much as from each endogenous mouse copy. These data provide new evidence that bacterial delivery is a convenient and efficient method to transfer large intact therapeutic genes into mammalian cells. PMID- 22095053 TI - Probiogenomics as a tool to obtain genetic insights into adaptation of probiotic bacteria to the human gut. AB - Bifidobacteria and lactobacilli are widely exploited as health-promoting bacteria in many functional foods. However, the molecular mechanisms as to how these bacteria positively impact on host health are far from completely understood. For this reason these microorganisms represent a growing area of interest with respect to their genomics, molecular biology and genetics. Recent genome sequencing of a large number of strains of bifidobacteria and lactobacilli has allowed access to the complete genetic makeup of representative members of these bacteria. Here, we will discuss how the analysis of genomic data has helped us to understand the mechanisms by which these bacteria adapt to the specific environment of the gastrointestinal tract, while also revealing genetic functions that mediate specific host-microbe interactions. PMID- 22095054 TI - Artificially designed promoters: understanding the role of spatial features and canonical binding sites in transcription. AB - The promoter is a key element in gene transcription and regulation. We previously reported that artificial sequences rich in the dinucleotide CpG are sufficient to drive expression in vitro in mammalian cell lines, without requiring canonical binding sites for transcription factor proteins. Here, we report that introducing a promoter organization that alternates in CpGs and regions rich in A and T further increases expression strength, as well as how insertion of specific binding sites makes such sequences respond to induced levels of the transcription factor NFkappaB. Our findings further contribute to the mechanistic understanding of promoters, as well as how these sequences might be shaped by evolutionary pressure in living organisms. PMID- 22095055 TI - Proteins: form and function. AB - An overwhelming array of structural variants has evolved from a comparatively small number of protein structural domains; which has in turn facilitated an expanse of functional derivatives. Herein, I review the primary mechanisms which have contributed to the vastness of our existing, and expanding, protein repertoires. Protein function prediction strategies, both sequence and structure based, are also discussed and their associated strengths and weaknesses assessed. PMID- 22095056 TI - [Perioperative coagulation management in microsurgery: report of the consensus workshops in the course of the 31st and 32nd Annual Meeting of the German language Working Group for microsurgery of the peripheral nerves and vessels (DAM) November 2009 in Erlangen and November 2010 in Basel]. AB - Microsurgery is a very relevant component of reconstructive surgery. In this context anticoagulation plays an increasing role. At the moment there are no unanimously accepted prospective studies or generally accepted regimes available that could serve as evidence-based guidelines for the prevention of thrombosis in microsurgery. With regard to this problem the aim of a series of workshops during the annual meetings of the German-speaking group for microsurgery in 2009 and 2010 was to establish a first possible consensus. This article reflects the main aspects of the ongoing development of a generally acceptable guideline for anticoagulation in microsurgery as interim report of these consensus workshops. Basically there are 3 main agents in thromboprophylaxis available: antiplatelet drugs, dextran and heparin. In the course of the workshops no general use of aspirin or dextran for anticoagulation in microsurgery was recommended. The use of heparin as anticoagulation agent is advisable for different indications. Low molecular heparins (LMH) have certain advantages in comparison to unfractionated heparins (UFH) and are therefore preferred by most participants. Indications for UFH are still complex microsurgical revisions, renal failure and some specific constellations in patients undergoing reconstruction of the lower extremity, where the continuous administration of heparin is recommended. At the moment of clamp release a single-shot of UFH is still given by many microsurgeons, despite a lack of scientific evidence. Future prospective clinical trials and the establishment of a generally accepted evidence-based guideline regarding anticoagulation treatment in microsurgery are deemed necessary. PMID- 22095057 TI - Psychological features and outcomes of the Back School treatment in patients with chronic non-specific low back pain. A randomized controlled study. AB - BACKGROUND: Low back pain is a worldwide health problem, affecting up to 80% of adult population. Psychological factors are involved in its development and maintenance. Many clinical trials have evaluated the efficacy of different interventions for chronic non-specific low back pain. In this field, Back School program has been demonstrated effective for people with chronic non-specific low back. AIM: To evaluate the relationship between the effects of the Back School treatment and psychological features measured by MMPI-II of patients with chronic non-specific low back pain. DESIGN: A randomised controlled trial with three and six-month follow-up. SETTING: Ambulatory rehabilitative university centre. POPULATION: Fifty patients with chronic non-specific low back pain out of 77 screened patients. METHODS: Patients were randomly placed in a 3:2 form and were allocated into two groups (Treatment versus Control). The Treatment Group participated to an intensive multidisciplinary Back School program (BSG, N.=29), while the Control Group received medical assistance (CG, N.=21). Medication was the same in both groups. Then, patients were subgrouped in those with at least an elevation in one scale of MMPI-II, and those without it. The Short Form 36 Health Status Survey for the assessment of quality of life (primary outcome measure), pain Visual Analogue Scale, Waddel Index and Oswestry Disability Index were collected at baseline, at the end of treatment, and at the three and six-month follow-up. RESULTS: Only the two treated subgroups showed a significant improvements in terms of quality of life, disability and pain. Among treated subjects, only those with at least one scale elevation in MMPI-II showed also a significant improvement in terms of Short Form 36 mental composite score and relevant subscores. CONCLUSION: These results suggest that Back School program has positive effects, even in terms of mental components of quality of life in patients with scale elevations of MMPI-II. Probably these findings are due to its educational and cognitive-behavioural characteristics. CLINICAL REHABILITATION IMPACT: Because of its educational purposes, the Back School treatment can have positive effects also on the mental status of patients with low back pain when it affects their psychological features. PMID- 22095058 TI - Experimenting with engagement : commentary on: Taking our own medicine: on an experiment in science communication. AB - Social scientists can explore questions about what counts as knowledge and how researchers-including social science researchers-can produce that knowledge. An art/space installation examining issues of public participation in science demonstrates the process of co-creation of knowledge about public participation, not simply the co-creation of the meaning of the installation itself. PMID- 22095059 TI - A national collaboration process: Finnish engineering education for the benefit of people and environment. AB - The key stakeholders of the Finnish engineering education collaborated during 2006-09 to reform the system of education, to face the challenges of the changing business environment and to create a national strategy for the Finnish engineering education. The work process was carried out using participatory work methods. Impacts of sustainable development (SD) on engineering education were analysed in one of the subprojects. In addition to participatory workshops, the core part of the work on SD consisted of a research with more than 60 interviews and an extensive literature survey. This paper discusses the results of the research and the work process of the Collaboration Group in the subproject of SD. It is suggested that enhancing systematic dialogue among key stakeholders using participatory work methods is crucial in increasing motivation and commitment in incorporating SD in engineering education. Development of the context of learning is essential for improving skills of engineering graduates in some of the key abilities related to SD: systemic- and life-cycle thinking, ethical understanding, collaborative learning and critical reflection skills. This requires changing of the educational paradigm from teacher-centred to learner centred applying problem- and project-oriented active learning methods. PMID- 22095060 TI - Ru(x)Pt(y)Sn(z) cluster-derived nanoparticle catalysts: spectroscopic investigation into the nature of active multinuclear single sites. AB - Cluster-derived Ru(x)Pt(y)Sn(z) nanoparticles are active catalysts in the hydrogenation of nitrobenzene. The nature of the active sites has been elucidated by FTIR spectroscopy using CO and NO as probe molecules. A new metal carbonyl cluster precursor, Pt(2)Ru(2)(SnBu(t)(3))(2)(CO)(9)(MU-H)(2), has been synthesized to obtain a Ru(2)Pt(2)Sn(2)/SiO(2) catalyst, that displayed remarkably high levels of conversion and selectivities compared to other bi-and monometallic analogues. Spectroscopic comparisons with Ru(5)PtSn/SiO(2) indicate that both the nature and the stoichiometry of the metals play a key role in modulating the catalytic activities and selectivities. A multinuclear single-site containing Pt centers, which facilitate the hydrogen activation, coupled with a highly reactive Ru site, possibly involved in the nitrobenzene activation, can be hypothesized. The oxophilicity of tin helps with the anchoring of the nanoparticles, aids the dispersion of the other metals, and can play an important role in influencing the selectivity to aniline. PMID- 22095062 TI - Hot flashes and cardiac vagal control during women's daily lives. AB - OBJECTIVE: The physiology of menopausal hot flashes is not well understood. The autonomic nervous system may play a role in hot flashes, but the current understanding is limited. We previously demonstrated in the laboratory that decreases in high-frequency heart rate variability, an index of cardiac vagal control, occur during hot flashes relative to preceding and following periods. In the present study, we tested whether we would observe a similar phenomenon in the ambulatory setting. We additionally considered respiratory rate in these associations. METHODS: Twenty-one perimenopausal and postmenopausal women aged 40 to 60 years reporting daily hot flashes were monitored both for physiologic and reported hot flashes and heart rate variability during a 24-hour period as they went about their daily lives. Heart rate variability estimates were derived using the band-limited variance method. The interval during the hot flash was compared with two nonflash periods before and after the hot flash via mixed-effects models. RESULTS: Heart rate variability significantly decreased during hot flashes relative to periods preceding (B = 0.31, SE = 0.03; P < 0.0001) and following (B = 0.30, SE = 0.03; P < 0.0001) physiologic hot flashes (covariates: age, race, education, menopause status, physical activity, body mass index, and anxiety). The findings were comparable considering self-reported hot flashes. They additionally persisted when controlling for respiratory rate. CONCLUSIONS: Significant decreases in cardiac vagal control occurred during hot flashes assessed during women's daily lives. These findings extend our work in the laboratory to the ambulatory setting, further shedding light on the physiology of hot flashes and underscoring a potential role of parasympathetic function in hot flashes. PMID- 22095063 TI - Gene expression: the dynamics of the brain transcriptome revealed. PMID- 22095065 TI - Brains on video games. AB - The popular press is replete with stories about the effects of video and computer games on the brain. Sensationalist headlines claiming that video games 'damage the brain' or 'boost brain power' do not do justice to the complexities and limitations of the studies involved, and create a confusing overall picture about the effects of gaming on the brain. Here, six experts in the field shed light on our current understanding of the positive and negative ways in which playing video games can affect cognition and behaviour, and explain how this knowledge can be harnessed for educational and rehabilitation purposes. As research in this area is still in its early days, the contributors of this Viewpoint also discuss several issues and challenges that should be addressed to move the field forward. PMID- 22095067 TI - Engaging, not excluding: a response to Walsh et al. PMID- 22095064 TI - Linking neurodevelopmental and synaptic theories of mental illness through DISC1. AB - Recent advances in our understanding of the underlying genetic architecture of psychiatric disorders has blown away the diagnostic boundaries that are defined by currently used diagnostic manuals. The disrupted in schizophrenia 1 (DISC1) gene was originally discovered at the breakpoint of an inherited chromosomal translocation, which segregates with major mental illnesses. In addition, many biological studies have indicated a role for DISC1 in early neurodevelopment and synaptic regulation. Given that DISC1 is thought to drive a range of endophenotypes that underlie major mental conditions, elucidating the biology of DISC1 may enable the construction of new diagnostic categories for mental illnesses with a more meaningful biological foundation. PMID- 22095069 TI - An X-ray microtomographic study of natural white-spot enamel lesions. AB - White-spot enamel lesions are an early presentation of dental caries and are ideally managed by non-invasive procedures. The aim of this study was to characterize white-spot enamel lesions by x-ray microtomography. In particular, mineral content across the lesion from the surface to the base of the lesion was measured and surface layers defined. Molars with long buccal white-spot enamel lesions were collected, photographed, and each sectioned to produce 3 500-um thick sections. The sections were mounted and imaged by quantitative x-ray microtomography at a 15-um voxel size. We analyzed line profiles through the middle of each 3D image to determine mineral content and depth. The surface layer thickness of the lesions ranged from 35 to 130 um, with the maximum mineral content in this layer being 74% to 100% of that of sound enamel. The average mineral content across the lesions ranged from 1.73 to 2.48 g/cm(3). No significant differences could be found between lesions clinically categorized as active and those categorized as inactive. However, for depth-matched active and inactive lesions, the active lesions exhibited a more porous surface layer than the inactive lesions. White-spot enamel lesions are highly variable, with surface layers of considerable thickness. PMID- 22095068 TI - Synergistic effects of bone mesenchymal stem cells and chondroitinase ABC on nerve regeneration after acellular nerve allograft in rats. AB - This study aimed to evaluate whether combination therapy of bone marrow stromal cells (BMSCs) transplantation and chondroitinase ABC (ChABC) treatment further enhances axonal regeneration and functional recovery after acellular nerve allograft repair of the sciatic nerve gap in rats. Eight Sprague-Dawley rats were used as nerve donors, and 32 Wistar rats were randomly divided into four groups: Group I: acellular rat sciatic nerve (ARSN) group; Group II: ChABC treatment; Group III: BMSCs transplantation; and Group IV: ChABC treatment and BMSCs transplantation. The results showed that compared with ARSN control group, BMSC transplantation promoted axonal regeneration, the secretion of neural trophic factors NGF, BDNF and axon angiogenesis in nerve graft. ChABC treatment degraded chondroitin sulfate proteoglycans in ARSN in vitro and in vivo and improved BMSCs survival in ARSN. The combination therapy caused much better beneficial effects evidenced by increasing sciatic function index, nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, and myelinated nerve number, but did not further boost the therapeutic effects on neurotrophic factor production, axon angiogenesis, and sensory functional recovery by BMSC transplantation. Taken together, for the first time, we demonstrate the synergistic effects of BMSC transplantation and BMSCs treatment on peripheral nerve regeneration, and our findings may help establish novel strategies for cell transplantation therapy for peripheral nerve injury. PMID- 22095072 TI - Tocotrienol as a potential anticancer agent. AB - Vitamin E is composed of two structurally similar compounds: tocopherols (TPs) and tocotrienols (T3). Despite being overshadowed by TP over the past few decades, T3 is now considered to be a promising anticancer agent due to its potent effects against a wide range of cancers. A growing body of evidence suggests that in addition to its antioxidative and pro-apoptotic functions, T3 possesses a number of anticancer properties that make it superior to TP. These include the inhibition of epithelial-to-mesenchymal transitions, the suppression of vascular endothelial growth factor tumor angiogenic pathway and the induction of antitumor immunity. More recently, T3, but not TP, has been shown to have chemosensitization and anti-cancer stem cell effects, further demonstrating the potential of T3 as an effective anticancer therapeutic agent. With most of the previous clinical studies on TP producing disappointing results, research has now focused on testing T3 as the next generation vitamin E for chemoprevention and cancer treatment. This review will summarize recent developments in the understanding of the anticancer effects of T3. We will also discuss current progress in clinical trials involving T3 as an adjuvant to conventional cancer therapy. PMID- 22095071 TI - Upregulation of CD9 in ovarian cancer is related to the induction of TNF-alpha gene expression and constitutive NF-kappaB activation. AB - Ovarian cancer is a gynecological cancer with a high death rate. We utilized global gene expression profiles of ovarian carcinomas obtained by complementary DNA (cDNA) microarray to identify ovarian cancer-specific proteins. CD9 was upregulated in ovarian carcinomas, and overexpression of the CD9 protein was detected in ovarian carcinomas by immunohistochemistry. CD9 was also overexpressed in several cancer cell lines, including ovarian cancer cells. In order to elucidate the biological significance of highly expressed CD9 in cancer cells, functional studies of CD9 were performed by ectopic expression, knockdown of CD9 using small interfering RNA (siRNA) and blockage of CD9 activity using the CD9-specific monoclonal antibody ALB6. Ectopic CD9 induced cell survival. In order to identify signaling pathways related to CD9, the gene expressions of CD9/SKOV3 cells were analyzed by cDNA microarray. Among the many upregulated genes, tumor necrosis factor (TNF)-alpha was induced in CD9/SKOV3 cells. The effect of overexpressed CD9 on the downstream signaling events of TNF-alpha was further investigated. In CD9/SKOV3 cells, the nuclear factor-kappaB (NF-kappaB) signaling pathway was constitutively activated. Knockdown of CD9 by siRNA and blockage of CD9 activity by ALB6 in ovarian cancer cells demonstrated that constitutive activation of NF-kappaB is CD9 dependent and that CD9 is involved in anti-apoptosis. A CD9 functional study was performed in an ovarian cancer xenograft mouse by injecting ALB6 into the peritoneum. ALB6 resulted in reduced tumor weight compared with that of control IgG(1). Collectively, these results demonstrate that CD9 functions as an oncogene and represents a target for the development of cancer-specific therapeutics. PMID- 22095070 TI - Viral gene transfer to developing mouse salivary glands. AB - Branching morphogenesis is essential for the formation of salivary glands, kidneys, lungs, and many other organs during development, but the mechanisms underlying this process are not adequately understood. Microarray and other gene expression methods have been powerful approaches for identifying candidate genes that potentially regulate branching morphogenesis. However, functional validation of the proposed roles for these genes has been severely hampered by the absence of efficient techniques to genetically manipulate cells within embryonic organs. Using ex vivo cultured embryonic mouse submandibular glands (SMGs) as models to study branching morphogenesis, we have identified new vectors for viral gene transfer with high efficiency and cell-type specificity to developing SMGs. We screened adenovirus, lentivirus, and 11 types of adeno-associated viruses (AAV) for their ability to transduce embryonic day 12 or 13 SMGs. We identified two AAV types, AAV2 and bovine AAV (BAAV), that are selective in targeting expression differentially to SMG epithelial and mesenchymal cell populations, respectively. Transduction of SMG epithelia with self-complementary (sc) AAV2 expressing fibroblast growth factor 7 (Fgf7) supported gland survival and enhanced SMG branching morphogenesis. Our findings represent, to our knowledge, the first successful selective gene targeting to epithelial vs. mesenchymal cells in an organ undergoing branching morphogenesis. PMID- 22095073 TI - Myofibroblast-induced tumorigenicity of pancreatic ductal epithelial cells is L1CAM dependent. AB - Pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis, representing one risk factor for PDAC, are characterized by a marked desmoplasia enriched of pancreatic myofibroblasts (PMFs). Thus, PMFs are thought to essentially promote pancreatic tumorigenesis. We recently demonstrated that the adhesion molecule L1CAM is involved in epithelial-mesenchymal transition of PMF-cocultured H6c7 human ductal epithelial cells and that L1CAM is expressed already in ductal structures of chronic pancreatitis with even higher elevation in primary tumors and metastases of PDAC patients. This study aimed at investigating whether PMFs and L1CAM drive malignant transformation of pancreatic ductal epithelial cells by enhancing their tumorigenic potential. Cell culture experiments demonstrated that in the presence of PMFs, H6c7 cells exhibit a profound resistance against death ligand-induced apoptosis. This apoptosis protection was similarly observed in H6c7 cells stably overexpressing L1CAM. Intrapancreatic inoculation of H6c7 cells together with PMFs (H6c7co) resulted in tumor formation in 7/8 and liver metastases in 6/8 severe combined immunodeficiency (SCID) mice, whereas no tumors and metastases were detectable after inoculation of H6c7 cells alone. Likewise, tumor outgrowth and metastases resulted from inoculation of L1CAM-overexpressing H6c7 cells in 5/7 and 3/7 SCID mice, respectively, but not from inoculation of mock-transfected H6c7 cells. Treatment of H6c7co tumor-bearing mice with the L1CAM antibody L1-9.3/2a inhibited tumor formation and liver metastasis in 100 and 50%, respectively, of the treated animals. Overall, these data provide new insights into the mechanisms of how PMFs and L1CAM contribute to malignant transformation of pancreatic ductal epithelial cells in early stages of pancreatic tumorigenesis. PMID- 22095074 TI - Guggulsterone induces heme oxygenase-1 expression through activation of Nrf2 in human mammary epithelial cells: PTEN as a putative target. AB - Guggulsterone (GS) [4,17(20)-pregnadiene-3,16-dione] is a phytosterol found in the gum resin of the Commiphora mukul. GS exists naturally in two stereoisomers: E-GS (cis-GS) and Z-GS (trans-GS). In this study, the effects of both isomers on expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) were evaluated in human mammary epithelial (MCF10A) cells. NF-E2-related factor 2 (Nrf2) is considered a master regulator in activating antioxidant response element (ARE) driven expression of HO-1 and many other antioxidant/cytoprotective proteins. cis GS upregulated the transcription and protein expression of HO-1 to a greater extent than did trans-GS. cis-GS treatment enhanced nuclear translocation and ARE binding activity of Nrf2. MCF10A cells transfected with an ARE luciferase construct exhibited significantly elevated Nrf2 transcriptional activity upon cis GS treatment compared with cells transfected with the control vector. In addition, silencing of the Nrf2 gene abrogated cis-GS-induced expression of HO-1. Incubation of MCF10A cells with cis-GS increased phosphorylation of Akt. The pharmacological inhibition of phosphoinositide 3-kinase (PI3K), an upstream kinase responsible for Akt phosphorylation, abrogated cis-GS-induced Nrf2 nuclear translocation. Pretreatment with the thiol-reducing agents attenuated Akt phosphorylation, Nrf2 activation and HO-1 expression, suggesting that cis-GS may cause thiol modification of an upstream signaling modulator. Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) is a negative regulator of the PI3K-Akt axis. The mutation in cysteine 124 present in the catalytic domain of PTEN abolished cis-GS-induced HO-1 expression as well as Akt phosphorylation. Whether this cysteine is a 'bona fide' target of cis-GS in its activation of Nrf2 needs additional investigation. PMID- 22095075 TI - [PSI+] Prion transmission barriers protect Saccharomyces cerevisiae from infection: intraspecies 'species barriers'. AB - [PSI+] is a prion of Sup35p, an essential translation termination and mRNA turnover factor. The existence of lethal [PSI+] variants, the absence of [PSI+] in wild strains, the mRNA turnover function of the Sup35p prion domain, and the stress reaction to prion infection suggest that [PSI+] is a disease. Nonetheless, others have proposed that [PSI+] and other yeast prions benefit their hosts. We find that wild Saccharomyces cerevisiae strains are polymorphic for the sequence of the prion domain and particularly in the adjacent M domain. Here we establish that these variations within the species produce barriers to prion transmission. The barriers are partially asymmetric in some cases, and evidence for variant specificity in barriers is presented. We propose that, as the PrP 129M/V polymorphism protects people from Creutzfeldt-Jakob disease, the Sup35p polymorphisms were selected to protect yeast cells from prion infection. In one prion incompatibility group, the barrier is due to N109S in the Sup35 prion domain and several changes in the middle (M) domain, with either the single N109S mutation or the group of M changes (without the N109S) producing a barrier. In another, the barrier is due to a large deletion in the repeat domain. All are outside the region previously believed to determine transmission compatibility. [SWI+], a prion of the chromatin remodeling factor Swi1p, was also proposed to benefit its host. We find that none of 70 wild strains carry this prion, suggesting that it is not beneficial. PMID- 22095076 TI - Inferring the history of interchromosomal gene transposition in Drosophila using n-dimensional parsimony. AB - Gene transposition puts a new gene copy in a novel genomic environment. Moreover, genes moving between the autosomes and the X chromosome experience change in several evolutionary parameters. Previous studies of gene transposition have not utilized the phylogenetic framework that becomes possible with the availability of whole genomes from multiple species. Here we used parsimonious reconstruction on the genomic distribution of gene families to analyze interchromosomal gene transposition in Drosophila. We identified 782 genes that have moved chromosomes within the phylogeny of 10 Drosophila species, including 87 gene families with multiple independent movements on different branches of the phylogeny. Using this large catalog of transposed genes, we detected accelerated sequence evolution in duplicated genes that transposed when compared to the parental copy at the original locus. We also observed a more refined picture of the biased movement of genes from the X chromosome to the autosomes. The bias of X-to-autosome movement was significantly stronger for RNA-based movements than for DNA-based movements, and among DNA-based movements there was an excess of genes moving onto the X chromosome as well. Genes involved in female-specific functions moved onto the X chromosome while genes with male-specific functions moved off the X. There was a significant overrepresentation of proteins involving chromosomal function among transposed genes, suggesting that genetic conflict between sexes and among chromosomes may be a driving force behind gene transposition in Drosophila. PMID- 22095077 TI - Multiple roles of the Cox20 chaperone in assembly of Saccharomyces cerevisiae cytochrome c oxidase. AB - The Cox2 subunit of Saccharomyces cerevisiae cytochrome c oxidase is synthesized in the mitochondrial matrix as a precursor whose leader peptide is rapidly processed by the inner membrane protease following translocation to the intermembrane space. Processing is chaperoned by Cox20, an integral inner membrane protein whose hydrophilic domains are located in the intermembrane space, and Cox20 remains associated with mature, unassembled Cox2. The Cox2 C tail domain is exported post-translationally by the highly conserved translocase Cox18 and associated proteins. We have found that Cox20 is required for efficient export of the Cox2 C-tail. Furthermore, Cox20 interacts by co-immune precipitation with Cox18, and this interaction requires the presence of Cox2. We therefore propose that Cox20 binding to Cox2 on the trans side of the inner membrane accelerates dissociation of newly exported Cox2 from the Cox18 translocase, promoting efficient cycling of the translocase. The requirement for Cox20 in cytochrome c oxidase assembly and respiratory growth is partially bypassed by yme1, mgr1 or mgr3 mutations, each of which reduce i-AAA protease activity in the intermembrane space. Thus, Cox20 also appears to stabilize unassembled Cox2 against degradation by the i-AAA protease. Pre-Cox2 leader peptide processing by Imp1 occurs in the absence of Cox20 and i-AAA protease activity, but is greatly reduced in efficiency. Under these conditions some mature Cox2 is assembled into cytochrome c oxidase allowing weak respiratory growth. Thus, the Cox20 chaperone has important roles in leader peptide processing, C-tail export, and stabilization of Cox2. PMID- 22095078 TI - Fine-scale estimation of location of birth from genome-wide single-nucleotide polymorphism data. AB - Systematic nonrandom mating in populations results in genetic stratification and is predominantly caused by geographic separation, providing the opportunity to infer individuals' birthplace from genetic data. Such inference has been demonstrated for individuals' country of birth, but here we use data from the Northern Finland Birth Cohort 1966 (NFBC1966) to investigate the characteristics of genetic structure within a population and subsequently develop a method for inferring location to a finer scale. Principal component analysis (PCA) shows that while the first PCs are particularly informative for location, there is also location information in the higher-order PCs, but it cannot be captured by a linear model. We introduce a new method, pcLOCATE, which is able to exploit this information to improve the accuracy of location inference. pcLOCATE uses individuals' PC values to estimate the probability of birth in each town and then averages over all towns to give an estimated longitude and latitude of birth using a fully Bayesian model. We apply pcLOCATE to the NFBC1966 data to estimate parental birthplace, testing with successively more PCs and finding the model with the top 23 PCs most accurate, with a median distance of 23 km between the estimated and the true location. pcLOCATE predicts the most recent residence of NFBC1966 individuals to a median distance of 47 km. We also apply pcLOCATE to Indian individuals from the London Life Sciences Prospective Population Study (LOLIPOP) data, and find that birthplace is predicated to a median distance of 54 km from the true location. A method with such accuracy is potentially valuable in population genetics and forensics. PMID- 22095080 TI - Fixation probability in a two-locus model by the ancestral recombination selection graph. AB - We use the ancestral influence graph (AIG) for a two-locus, two-allele selection model in the limit of a large population size to obtain an analytic approximation for the probability of ultimate fixation of a single mutant allele A. We assume that this new mutant is introduced at a given locus into a finite population in which a previous mutant allele B is already segregating with a wild type at another linked locus. We deduce that the fixation probability increases as the recombination rate increases if allele A is either in positive epistatic interaction with B and allele B is beneficial or in no epistatic interaction with B and then allele A itself is beneficial. This holds at least as long as the recombination fraction and the selection intensity are small enough and the population size is large enough. In particular this confirms the Hill-Robertson effect, which predicts that recombination renders more likely the ultimate fixation of beneficial mutants at different loci in a population in the presence of random genetic drift even in the absence of epistasis. More importantly, we show that this is true from weak negative epistasis to positive epistasis, at least under weak selection. In the case of deleterious mutants, the fixation probability decreases as the recombination rate increases. This supports Muller's ratchet mechanism to explain the accumulation of deleterious mutants in a population lacking recombination. PMID- 22095081 TI - Frameshift mutagenesis: the roles of primer-template misalignment and the nonhomologous end-joining pathway in Saccharomyces cerevisiae. AB - Small insertions or deletions that alter the reading frame of a gene typically occur in simple repeats such as mononucleotide runs and are thought to reflect spontaneous primer-template misalignment during DNA replication. The resulting extrahelical repeat is efficiently recognized by the mismatch repair machinery, which specifically replaces the newly replicated strand to restore the original sequence. Frameshift mutagenesis is most easily studied using reversion assays, and previous studies in Saccharomyces cerevisiae suggested that the length threshold for polymerase slippage in mononucleotide runs is 4N. Because the probability of slippage is strongly correlated with run length, however, it was not clear whether shorter runs were unable to support slippage or whether the resulting frameshifts were obscured by the presence of longer runs. To address this issue, we removed all mononucleotide runs >3N from the yeast lys2DeltaBgl and lys2DeltaA746 frameshift reversion assays, which detect net 1-bp deletions and insertions, respectively. Analyses demonstrate that 2N and 3N runs can support primer-template misalignment, but there is striking run-specific variation in the frequency of slippage, in the accumulation of +1 vs. -1 frameshifts and in the apparent efficiency of mismatch repair. We suggest that some of this variation reflects the role of flanking sequence in initiating primer-template misalignment and that some reflects replication-independent frameshifts generated by the nonhomologous end-joining pathway. Finally, we demonstrate that nonhomologous end joining is uniquely required for the de novo creation of tandem duplications from noniterated sequence. PMID- 22095079 TI - The double-bromodomain proteins Bdf1 and Bdf2 modulate chromatin structure to regulate S-phase stress response in Schizosaccharomyces pombe. AB - Bromodomain proteins bind acetylated histones to regulate transcription. Emerging evidence suggests that histone acetylation plays an important role in DNA replication and repair, although its precise mechanisms are not well understood. Here we report studies of two double bromodomain-containing proteins, Bdf1 and Bdf2, in fission yeast. Loss of Bdf1 or Bdf2 led to a reduction in the level of histone H4 acetylation. Both bdf1Delta and bdf2Delta cells showed sensitivity to DNA damaging agents, including camptothecin, that cause replication fork breakage. Consistently, Bdf1 and Bdf2 were important for recovery of broken replication forks and suppression of DNA damage. Surprisingly, deletion of bdf1 or bdf2 partially suppressed sensitivity of various checkpoint mutants including swi1Delta, mrc1Delta, cds1Delta, crb2Delta, chk1Delta, and rad3Delta, to hydroxyurea, a compound that stalls replication forks and activates the Cds1 dependent S-phase checkpoint. This suppression was not due to reactivation of Cds1. Instead, we found that bdf2 deletion alleviates DNA damage accumulation caused by defects in the DNA replication checkpoint. We also show that hydroxyurea sensitivity of mrc1Delta and swi1Delta was suppressed by mutations in histone H4 acetyltransferase subunits or histone H4. These results suggest that the double bromodomain-containing proteins modulate chromatin structure to coordinate DNA replication and S-phase stress response. PMID- 22095082 TI - A conserved transcriptional regulator governs fungal morphology in widely diverged species. AB - Fungi exhibit a large variety of morphological forms. Here, we examine the functions of a deeply conserved regulator of morphology in three fungal species: Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae are transcriptional regulators that recognize the same DNA sequence. Previous work established that Wor1 regulates white-opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae is also a master regulator of a morphological transition, in this case pseudohyphal growth. Full-genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of the previously known regulators of pseudohyphal growth as well as those of many additional genes. Through a comparison of binding sites for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that the genes controlled by the orthologous regulators overlap only slightly between these two species despite the fact that the DNA binding specificity of the regulators has remained largely unchanged. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species. PMID- 22095084 TI - Stickbreaking: a novel fitness landscape model that harbors epistasis and is consistent with commonly observed patterns of adaptive evolution. AB - In relating genotypes to fitness, models of adaptation need to both be computationally tractable and qualitatively match observed data. One reason that tractability is not a trivial problem comes from a combinatoric problem whereby no matter in what order a set of mutations occurs, it must yield the same fitness. We refer to this as the bookkeeping problem. Because of their commutative property, the simple additive and multiplicative models naturally solve the bookkeeping problem. However, the fitness trajectories and epistatic patterns they predict are inconsistent with the patterns commonly observed in experimental evolution. This motivates us to propose a new and equally simple model that we call stickbreaking. Under the stickbreaking model, the intrinsic fitness effects of mutations scale by the distance of the current background to a hypothesized boundary. We use simulations and theoretical analyses to explore the basic properties of the stickbreaking model such as fitness trajectories, the distribution of fitness achieved, and epistasis. Stickbreaking is compared to the additive and multiplicative models. We conclude that the stickbreaking model is qualitatively consistent with several commonly observed patterns of adaptive evolution. PMID- 22095083 TI - A screen for X-linked mutations affecting Drosophila photoreceptor differentiation identifies Casein kinase 1alpha as an essential negative regulator of wingless signaling. AB - The Wnt and Hedgehog signaling pathways are essential for normal development and are misregulated in cancer. The casein kinase family of serine/threonine kinases regulates both pathways at multiple levels. However, it has been difficult to determine whether individual members of this family have distinct functions in vivo, due to their overlapping substrate specificities. In Drosophila melanogaster, photoreceptor differentiation is induced by Hedgehog and inhibited by Wingless, providing a sensitive system in which to identify regulators of each pathway. We used a mosaic genetic screen in the Drosophila eye to identify mutations in genes on the X chromosome required for signal transduction. We recovered mutations affecting the transcriptional regulator CREB binding protein, the small GTPase dynamin, the cytoskeletal regulator Actin-related protein 2, and the protein kinase Casein kinase 1alpha. Consistent with its reported function in the beta-Catenin degradation complex, Casein Kinase 1alpha mutant cells accumulate beta-Catenin and ectopically induce Wingless target genes. In contrast to previous studies based on RNA interference, we could not detect any effect of the same Casein Kinase 1alpha mutation on Hedgehog signaling. We thus propose that Casein kinase 1alpha is essential to allow beta-Catenin degradation and prevent inappropriate Wingless signaling, but its effects on the Hedgehog pathway are redundant with other Casein kinase 1 family members. PMID- 22095085 TI - MicroRNA transgene overexpression complements deficiency-based modifier screens in Drosophila. AB - Dosage-sensitive modifier screening is a powerful tool for linking genes to biological processes. Use of chromosomal deletions permits sampling the effects of removing groups of genes related by position on the chromosome. Here, we explore the use of inducible microRNA transgenes as a complement to deficiency based modifier screens. miRNAs are predicted to have hundreds of targets. miRNA overexpression provides an efficient means to reduces expression of large gene sets. A collection of transgenes was prepared to allow overexpression of 89 miRNAs or miRNA clusters. These transgenes and a set of genomic deficiencies were screened for their ability to modify the bristle phenotype of the cell-cycle regulator minus. Sixteen miRNAs were identified as dominant suppressors, while the deficiency screen uncovered four genomic regions that contain a dominant suppressor. Comparing the genes uncovered by the deletions with predicted miRNA targets uncovered a small set of candidate suppressors. Two candidates were identified as suppressors of the minus phenotype, Cullin-4 and CG5199/Cut8. Additionally, we show that Cullin-4 acts through its substrate receptor Cdt2 to suppress the minus phenotype. We suggest that inducible microRNA transgenes are a useful complement to deficiency-based modifier screens. PMID- 22095088 TI - Effects of proteasome inhibitors on the nucleolar size of porcine oocytes. AB - During the final stage of oocyte growth, the morphology of the oocyte nucleoli changes into a compact structure. The objective of this study was to determine the involvement of the proteasome, which is a large protein complex responsible for degrading intracellular proteins, in the nucleolar compaction. The mean nucleolar diameter of growing porcine oocytes (about 100 um in diameter) was larger than that of fully grown (120 um) oocytes (15.5 +/- 0.3 vs. 13.2 +/- 0.1 um, P<0.05). When fully grown oocytes were treated with proteasome inhibitors, MG132 (10 and 20 uM) and lactacystin (100 and 200 uM), the nucleolar diameter significantly increased from 12.9 um to 14.9-16.1 um. In contrast, transcription inhibitors, actinomycin D (0.8-8 uM) and alpha-amanitin (10-100 uM) reduced the nucleolar diameter of growing oocytes to 9.4-12.4 um. MG132 partially prevented this reduction in nucleolar diameter. These results suggest that the proteasome regulates the nucleolar size in porcine oocytes perhaps through the degradation of nucleolar proteins. PMID- 22095087 TI - High-resolution structure of shikimate dehydrogenase from Thermotoga maritima reveals a tightly closed conformation. AB - Shikimate dehydrogenase (SDH), which catalyses the NADPH-dependent reduction of 3 dehydroshikimate to shikimate in the shikimate pathway, is an attractive target for the development of herbicides and antimicrobial agents. Structural analysis of a SDH from Thermotoga maritima encoded by the Tm0346 gene was performed to facilitate further structural comparisons between the various shikimate dehydrogenases. The crystal structure of SDH from T. maritima was determined at 1.45 SDH from T. maritima showed a monomeric architecture. The overall structure of SDH from T. maritima comprises the N-terminal alpha/beta sandwich domain for substrate binding and the C-terminal domain for NADP binding. When the T. maritima SDH structure was compared with those of the SDHs from other species, the SDH from T. maritima was in a tightly closed conformation, which should be open for catalysis. Notably, alpha7 moves toward the active site (~5 A), which forces the SDH of T. maritima in a more closed form. Four ammonium sulfate (AMS) ions were identified in the structure. They were located in the active site and appeared to mimic the role of the substrate in terms of the enzyme activity and stability. The new high resolution structural information reported in this study, including the AMS binding sites as a potent inhibitor binding site of SDHs, is expected to supplement the existing structural data and will be useful for structure-based antibacterial discovery against SDHs. PMID- 22095086 TI - Huntingtin aggregation kinetics and their pathological role in a Drosophila Huntington's disease model. AB - Huntington's disease is a neurodegenerative disorder resulting from expansion of a polyglutamine tract in the Huntingtin protein. Mutant Huntingtin forms intracellular aggregates within neurons, although it is unclear whether aggregates or more soluble forms of the protein represent the pathogenic species. To examine the link between aggregation and neurodegeneration, we generated Drosophila melanogaster transgenic strains expressing fluorescently tagged human huntingtin encoding pathogenic (Q138) or nonpathogenic (Q15) proteins, allowing in vivo imaging of Huntingtin expression and aggregation in live animals. Neuronal expression of pathogenic Huntingtin leads to pharate adult lethality, accompanied by formation of large aggregates within the cytoplasm of neuronal cell bodies and neurites. Live imaging and Fluorescence Recovery After Photobleaching (FRAP) analysis of pathogenic Huntingtin demonstrated that new aggregates can form in neurons within 12 hr, while preexisting aggregates rapidly accumulate new Huntingtin protein within minutes. To examine the role of aggregates in pathology, we conducted haplo-insufficiency suppressor screens for Huntingtin-Q138 aggregation or Huntingtin-Q138-induced lethality, using deficiencies covering ~80% of the Drosophila genome. We identified two classes of interacting suppressors in our screen: those that rescue viability while decreasing Huntingtin expression and aggregation and those that rescue viability without disrupting Huntingtin aggregation. The most robust suppressors reduced both soluble and aggregated Huntingtin levels, suggesting toxicity is likely to be associated with both forms of the mutant protein in Huntington's disease. PMID- 22095089 TI - Antinociceptive and anti-inflammatory activities of Satureja hortensis seed essential oil, hydroalcoholic and polyphenolic extracts in animal models. AB - OBJECTIVE: The aim of this study was to evaluate the anti-inflammatory and analgesic effects of Satureja hortensis seed extracts and to analyze their essential oil constituents. MATERIALS AND METHODS: Hydroalcoholic and polyphenolic extracts and essential oil of S. hortensis seeds were prepared using standard methods. Analgesic activity was assessed in male mice (25-35 g) using standard methods (acetic acid and formalin tests). For the evaluation of anti inflammatory activity, the carrageenan-induced rat paw edema test was used. The mice were pretreated with 50, 100 or 200 mg/kg, i.p., hydroalcoholic or polyphenolic extracts or 100 or 200 MUl/kg, p.o. RESULTS: Hydrodistillation of the seeds of S. hortensis afforded a pale yellowish oil in a yield of 0.05% (v/w). Pretreatment of mice with hydroalcoholic or polyphenolic extracts or essential oil significantly (p < 0.001) reduced acetic acid-induced abdominal twitches. Hydroalcoholic extracts also significantly reduced pain responses in early and late phases of the formalin test whereas the polyphenolic extract and essential oil were only effective in the late phase of the formalin test. All three fractions were found to reduce paw edema in the carrageenan test. CONCLUSION: These results clearly demonstrate the analgesic and anti-inflammatory activity of S. hortensis seeds and since the hydroalcoholic extract relieved pain in the first phase of the formalin test, it seems that at least part of its analgesic activity may be mediated centrally. The results of this study substantiated the traditional use of S. hortensis plant seeds in painful and inflammatory ailments. PMID- 22095090 TI - Neuroprotective effects of Salidroside and its analogue tyrosol galactoside against focal cerebral ischemia in vivo and H2O2-induced neurotoxicity in vitro. AB - Salidroside (Sal) is a natural antioxidant extracted from the root of Rhodiola rosea L. that elicits neuroprotective effects in vivo and in vitro. Tyrosol galactoside (Tyr), an analog of Sal, was recently synthesized in our laboratory. The purpose of the current study was to investigate and compare the neuroprotective effects of Sal and Tyr against focal cerebral ischemia in vivo and H(2)O(2)-induced neurotoxicity in vitro. Sal and Tyr significantly prevented a cerebral ischemic injury induced by a 2 h middle cerebral artery occlusion and a 24 h reperfusion in rats in vivo. Furthermore, the oxidative insult was markedly attenuated by treatments of Sal and Tyr in the cultured rat cortical neurons after a 30 min exposure to 50 MUM of H(2)O(2). Western blot analysis revealed that Sal and Tyr decreased the expression of Bax and restored the balance of pro- and anti-apoptotic proteins. The neuroprotective effects of these two analogues show that Tyr has a better antioxidative action compared with Sal both in vivo and in vitro, and suggest that the antioxidant activity of Sal and Tyr may be partly due to their different substituents in their glycosyl groups. This gives a new insight into the development of therapeutic natural antioxidants against oxidative stress. PMID- 22095092 TI - CAF05: cationic liposomes that incorporate synthetic cord factor and poly(I:C) induce CTL immunity and reduce tumor burden in mice. AB - Considerable effort has been put into targeting tumors through therapeutic vaccination using dendritic cell-, DNA-, protein-, or peptide-based vaccines. Purified peptides and proteins are generally not immunogenic and need to be administered with an adjuvant that will trigger an appropriate immune response. Safe adjuvants that favor induction of tumor reactive CD8(+) T cells with the capacity to directly kill tumor cells are therefore a high priority. We have previously reported on the effect and mechanism of a cationic adjuvant formulation, CAF01, which incorporates synthetic mycobacterial cord factor and primes protective Th1, Th17, and antibody responses in animal models of bacterial, viral, and parasitic infections. The CAF01 adjuvant is currently in clinical trial. Using CAF01 as a backbone, we recently demonstrated that incorporating the TLR3 ligand polyinosinic/polycytidylic acid [poly(I:C)] primes CD8(+) T cells specific to the SIINFEKL epitope of the model antigen ovalbumin. In the present study, we demonstrate that CAF01/poly(I:C), termed cationic adjuvant formulation 05 or CAF05, can induce CD8(+) T cells that efficiently lyse target cells and significantly reduce tumor growth in two different mouse tumor models: lung B16-OVA melanoma expressing ovalbumin and the self-antigen TRP2, and subcutaneous TC-1 tumors expressing the human papillomavirus-16 protein E7. PMID- 22095094 TI - Tick-borne encephalitis virus: reference strain Sofjin and problem of its authenticity. AB - The Sofjin strain is one of the first isolates of tick-borne encephalitis virus and, due to its wide distribution in virus collections, it has become the reference strain. Until now, GenBank has recorded several sequences associated with the Sofjin strain that have significant differences between each other. We have sequenced the complete genome of the Sofjin strain from a virus collection and a genome fragment of the two vaccine Sofjin strains. According to phylogenetic analysis, we concluded that the GenBank sequences belong to three independent groups of Sofjin strains of the Far Eastern subtype. Their genetic differences are not a result of microevolution associated with numerous passages. Retrospective analysis of the peculiarities of origin and distribution for each of these groups showed the authenticity of one of them. For the first time, we have determined a complete genome sequence of the authentic reference TBEV strain Sofjin. Two other groups of strains named Sofjin were probably the result of cross-contamination or laboratory error. The high probability of contamination requires the introduction of a new standard for virological laboratories, the key point of which is the obligatory genetic identification of all collection strains. PMID- 22095093 TI - Retinal sensitivity after resolution of the macular edema associated with retinal vein occlusion. AB - PURPOSE: To study the correlation of retinal sensitivity with both morphologic changes in the macula and status of retinal capillary perfusion, after resolution of the macular edema associated with retinal vein occlusion (RVO). METHODS: Retinal sensitivity in the macular area was examined with the Micro Perimeter 1 in 24 eyes after resolution of the macular edema associated with RVO. Using spectral-domain optical coherence tomography, 6 mm * 6 mm areas of macula were examined with 256 sequential horizontal scans. Condition of the photoreceptor layer was evaluated depending upon detection of the junctions between inner and outer segments of the photoreceptors (IS/OS). Fluorescein angiography was performed in 19 eyes. RESULTS: Mean retinal sensitivity on the affected side of the retina was significantly decreased (p < 0.001). On the affected side, the mean retinal sensitivity within the area of deteriorated IS/OS was significantly less (3.8 +/- 4.8 dB) than that within areas with complete IS/OS (10.1 +/- 6.4 dB, p < 0.001). Mean retinal sensitivity within nonperfused areas was extremely low (0.3 +/- 1.3 dB), compared with that in perfused retina (10.9 +/- 5.9 dB, p < 0.001). In eyes with a broken foveal capillary ring (FCR), the marked decline in retinal sensitivity was seen within the area where the FCR was broken; this was not seen in eyes with an intact FCR. CONCLUSION: Retinal function was decreased markedly in areas with a damaged photoreceptor layer due to RVO, and was lethally decreased within nonperfused areas. Due to the various limitations of the current study, including implementation of fluorescein angiography in limited number of eyes, wide range of follow-up, and heterogeneity of pretreatments, further prospective studies are necessary to confirm the current findings. PMID- 22095091 TI - Zinc and the ERK kinases in the developing brain. AB - This article reviews evidence in support of the hypothesis that impaired activation of the extracellular signal-regulated kinases (ERK1/2) contributes to the disruptions in neurodevelopment associated with zinc deficiency. These kinases are implicated in major events of brain development, including proliferation of progenitor cells, neuronal migration, differentiation, and apoptotic cell death. In humans, mutations in ERK1/2 genes have been associated with neuro-cardio-facial-cutaneous syndromes. ERK1/2 deficits in mice have revealed impaired neurogenesis, altered cellularity, and behavioral abnormalities. Zinc is an important modulator of ERK1/2 signaling. Conditions of both zinc deficiency and excess affect ERK1/2 phosphorylation in fetal and adult brains. Hypophosphorylation of ERK1/2, associated with decreased zinc availability in cell cultures, is accompanied by decreased proliferation and an arrest of the cell cycle at the G0/G1 phase. Zinc and ERK1/2 have both been shown to modulate neural progenitor cell proliferation and cell death in the brain. Furthermore, behavioral deficits resulting from developmental zinc deficiency are similar to those observed in mice with decreased ERK1/2 signaling. For example, impaired performance on behavioral tests of learning and memory; such as the Morris water maze, fear conditioning, and the radial arm maze; has been reported in both animals exposed to developmental zinc deficiency and transgenic mice with decreased ERK signaling. Future study should clarify the mechanisms through which a dysregulation of ERK1/2 may contribute to altered brain development associated with dietary zinc deficiency and with conditions that limit zinc availability. PMID- 22095097 TI - [100] Directed Cu-doped h-CoO nanorods: elucidation of the growth mechanism and application to lithium-ion batteries. AB - Thermal decomposition of Co(acac)(3) and Cu(acac)(2) in benzylamine leads to the formation of [100] directed Cu-doped h-CoO nanorods, which are very stable in an aqueous solution. The formation mechanism of the [100] directed Cu-doped h-CoO nanorods is fully elucidated by using first-principles calculations, demonstrating that Cu-doping not only changes the growth direction but also enhances the stability of the nanorods significantly. Evaluation of the electrochemical performance of Cu-doped h-CoO nanorods shows high initial Coulombic efficiency and ultrahigh capacity with excellent cycling performance, indicating their suitability as an anode material for next generation lithium-ion batteries. PMID- 22095096 TI - Controlled release of IGF-I from a biodegradable matrix improves functional recovery of skeletal muscle from ischemia/reperfusion. AB - Ischemia/reperfusion (I/R) injury is a considerable insult to skeletal muscle, often resulting in prolonged functional deficits. The purpose of the current study was to evaluate the controlled release of the pro-regenerative growth factor, insulin-like growth factor-I (IGF-I), from a biodegradable polyethylene glycol (PEG)ylated fibrin gel matrix and the subsequent recovery of skeletal muscle from I/R. To accomplish this, the hind limbs of male Sprague-Dawley rats were subjected to 2-h tourniquet-induced I/R then treated with saline, bolus IGF I (bIGF), PEGylated fibrin gel (PEG-Fib), or IGF-I conjugated PEGylated fibrin gel (PEG-Fib-IGF). Functional and histological evaluations were performed following 14 days of reperfusion, and muscles from 4-day reperfusion animals were analyzed by Western blotting and histological assessments. There was no difference in functional recovery between saline, bIGF, or PEG-Fib groups. However, PEG-Fib-IGF treatment resulted in significant improvement of muscle function and structure, as observed histologically. Activation of the PI3K/Akt pathway was significantly elevated in PEG-Fib-IGF muscles, compared to PEG-Fib treatment, at 4 days of reperfusion, suggesting involvement of the pathway PI3K/Akt as a mediator of the improved function. Surprisingly, myoblast activity was not evident as a result of PEG-Fib-IGF treatment. Taken together, these data give evidence for a protective role for the delivered IGF. These results indicate that PEG-Fib-IGF is a viable therapeutic technique in the treatment of skeletal muscle I/R injury. PMID- 22095098 TI - Association of cognitive function and risk for elder abuse in a community dwelling population. AB - AIM: This study aimed to examine the cross-sectional association between cognitive function and elder abuse. METHODS: The Chicago Health and Aging Project (CHAP) is a population-based study conducted in a geographically defined community (n = 8,932). We identified 238 CHAP participants who had elder abuse reported to a social services agency. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (perceptual speed), and both immediate and delayed recall of the East Boston Memory Test (episodic memory). An index of global cognitive function scores was derived by averaging the z-scores of all tests. Logistic regression models were used to assess the association of cognitive function domains and risk of elder abuse. RESULTS: After adjusting for confounders, lowest tertiles of global cognition (odd's ratio, OR 4.18, 95% confidence interval, 95% CI 2.44-7.15), MMSE (OR 2.97, 95% CI 1.93-4.57), episodic memory (OR 2.27, 95% CI 1.49-3.43) and perceptual speed (OR 2.37, 95% CI 1.51-3.73) were associated with increased risk of elder abuse. The lowest levels of global cognitive function were associated with an increased risk of physical abuse (OR 3.56, 95% CI 1.08-11.67), emotional abuse (OR 3.02, 95% CI 1.41-6.44), caregiver neglect (OR 6.24, 95% CI 2.68 14.54), and financial exploitation (OR 3.71, 95% CI 1.88-7.32). CONCLUSION: Lower levels of global cognitive function, MMSE, episodic memory and perceptual speed are associated with an increased risk of elder abuse. PMID- 22095099 TI - Aldosterone and the heart: from basic research to clinical evidence. AB - Recent views suggest that long-term exposure to elevated aldosterone concentrations might result in cardiac, vascular, renal, and metabolic sequelae that occur independent of the blood pressure level. Indirect evidence of the untoward effects of aldosterone on the heart has been clearly established in clinical studies that have tested the effects of mineralocorticoid receptor antagonists in the treatment of systolic heart failure. As it has become clear in recent years, the interaction between aldosterone and the heart has to deal with additional actions of the hormone on specific cell types, cellular mechanisms, and molecules that are involved in regulation of tissue responses, leading to hypertrophy, remodeling, and fibrosis. The majority of these effects are mediated by activation of the mineralocorticoid receptors that are expressed in cardiomyocytes and cardiac fibroblasts, and mediate the genomic effects of the hormone. Evidence of interactions between aldosterone and the heart that occur independent of the renal effects of aldosterone, however, is not limited to the context of systolic heart failure and observations obtained in other disease states have led, together with findings of animal studies, to a better understanding of the potential benefits of aldosterone antagonists. In this narrative overview, we highlight the most recent findings that have been obtained in experimental animal models and in clinical conditions that include, in addition to systolic heart failure, primary aldosteronism, essential hypertension, diastolic heart failure, and arrhythmia. PMID- 22095100 TI - Salivary transcriptomic biomarkers for detection of ovarian cancer: for serous papillary adenocarcinoma. AB - Ovarian cancer is the most lethal gynecological cancer due to lack of clear symptom and reliable screening biomarker in the early stage. The capability to detect the initiation of malignancy with a sensitive and effective approach is one of the most desirable goals for ovarian cancer therapy. In this study, we spearheaded noninvasive detection of ovarian cancer by salivary transcriptomic biomarkers, and evaluated the clinical utilities of discovered biomarkers using a clinical case-control study. To find salivary mRNA biomarkers, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled by Affymetrix HG-U133-Plus-2.0 array. The biomarker candidates selected from the microarray results were then subjected to clinical validation by RT-qPCR using an independent sample cohort including 21 ovarian cancer patients and 35 healthy controls. Seven downregulated mRNA biomarkers were validated. The logistic regression model revealed the combination of five validated biomarkers (AGPAT1, B2M, BASP2, IER3, and IL1B) can significantly discriminate ovarian cancer patients (n = 21) from the healthy controls (n = 35), yielding a receiver operating characteristic plot, area under the curve value of 0.909 with 85.7% sensitivity and 91.4% specificity. In summary, we have demonstrated that the RNA signatures in saliva could serve as biomarkers for detection of ovarian cancer with high sensitivity and specificity. This emerging approach with high throughput, noninvasive, and effective advantages provides a feasible means for detection of systemic cancer, and opens a new avenue for early disease detection. PMID- 22095101 TI - Comparative kinome analysis to identify putative colon tumor biomarkers. AB - Kinase domains are the type of protein domain most commonly found in genes associated with tumorigenesis. Because of this, the human kinome (the protein kinase component of the genome) represents a promising source of cancer biomarkers and potential targets for novel anti-cancer therapies. Alterations in the human colon kinome during the progression from normal colon (NC) through adenoma (AD) to adenocarcinoma (AC) were investigated using integrated transcriptomic and proteomic datasets. Two hundred thirty kinase genes and 42 kinase proteins showed differential expression patterns (fold change >= 1.5) in at least one tissue pair-wise comparison (AD vs. NC, AC vs. NC, and/or AC vs. AD). Kinases that exhibited similar trends in expression at both the mRNA and protein levels were further analyzed in individual samples of NC (n = 20), AD (n = 39), and AC (n = 24) by quantitative reverse transcriptase PCR. Individual samples of NC and tumor tissue were distinguishable based on the mRNA levels of a set of 20 kinases. Altered expression of several of these kinases, including chaperone activity of bc1 complex-like (CABC1) kinase, bromodomain adjacent to zinc finger domain protein 1B (BAZ1B) kinase, calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D), serine/threonine-protein kinase 24 (STK24), vaccinia-related kinase 3 (VRK3), and TAO kinase 3 (TAOK3), has not been previously reported in tumor tissue. These findings may have diagnostic potential and may lead to the development of novel targeted therapeutic interventions for colorectal cancer. PMID- 22095103 TI - Preventive non-invasive ventilation is indicated for neuromuscular disease patients after extubation. PMID- 22095102 TI - Comparison of newer scoring systems with the conventional scoring systems in general intensive care population. AB - BACKGROUND: The aim of this study was to assess the performance of Acute Physiology and Chronic Health Evaluation (APACHE) IV, Simplified Acute Physiology Score (SAPS) III, and Mortality Probability Model (MPM) III0 and compare these systems to more widely validated prognosis prediction tools like APACHE II, III, SAPS II, MPM II0 and Sequential Organ Failure Assessment (SOFA) score. METHODS: The study provided a retrospective analysis of data for all consecutive patients admitted to a medical ICU over a 15-month period. Data related to patient demographics, and that necessary to compute various scores were recorded. Calibration was assessed by calculating Lemeshow-Hosmer goodness-of-fit test. Discrimination was evaluated by calculating the area under curves (AUC). Primary outcome measure was Intensive Care Unit mortality. RESULTS: Mortality predicted by APACHE IV score was closest to that of actual mortality with a SMR of 0.868 followed by that of MPM III0 (0.794) and SAPS III (0.763) scores. APACHE III (chi2=3.674), with P=0.885 had the best calibration followed by APACHE II (chi2=7.959; P=0.438) and SOFA scores (chi2=8.369; P=0.301). All scores had good efficacy and even though there was no significant difference between AUCs of various scores, MPM III0 (0.947) performed the best followed by APACHE IV (0.928) and MPM II0 (0.928). CONCLUSION: Overall, the newer scoring systems performed better than their older counterparts and were more accurate. Nevertheless, the difference in efficacy was not statistically significant and the choice of scoring system may depend on the ease of use and local preferences. PMID- 22095104 TI - Gravity may be the law, but it does not impact critical illness related carriage in overgrowth. PMID- 22095105 TI - Lactate: a friendly fuel for the injured brain? PMID- 22095106 TI - Acute and chronic pain: where we are and where we have to go. AB - In recent years, increasing attention has been focused on the treatment of acute and chronic pain with a considerable number of publications about it. Nevertheless all the attention focused on it, the evidence of pain treatments is still unfolding, and occasionally conflicting. Hence it is still necessary that we point out our research efforts in trying to obtain a better understand of pathophysiology of pain and of real efficacy and safety of acute and chronic pain treatments. Our goal with this review is to summarize the latest research trends and the most advanced therapeutic standards for pain syndromes described in the literature, the discussion will be divided in four main topics, as these topics were treated during the SIMPAR (Study In Multidisciplinary PAin Research) meeting, held on December 2010 in Pavia: pathophysiology of pain, acute postoperative pain, opioids and pain, and chronic pain (Failed Back Surgery Syndrome). In the chapter of pathophysiology of pain we analyzed how to obtain a more personalized treatment through the study of the genetic and neurophysiological characteristics of patients and how to select the right local anesthetic according to anatomic and metabolizing patterns of patients. In acute postoperative pain we focalized our attention on the evidence supporting the use of continuous peripheral nerve blocks in the treatment of postoperative pain and in the prevention of chronic persistent post-operative pain, with a special attention in preventing side effects of regional anesthesia. We also reviewed the current evidence about the use of new very interesting modality to control postoperative pain after laparoscopy: pre-emptive nebulization of local anesthetic in abdominal cavity. As opioids are currently widely used to control chronic oncologic and non-oncologic pain, in this review we analyzed the level of evidence for their use, how to manage them better and psychological factors that can affect their success and/or determine addiction. Finally, we summarized the current evidence about Failed Back Surgery Syndrome focalizing our attention both in diagnosing it correctly and treating this syndrome with specific knowledge of the anatomic space that we have to approach and applying the possible treatments depending on pain pathophysiology and patient characteristics. In conclusion, it is important to try to personalize even better the therapy of patients with acute and chronic pain through a more accurate knowledge of anatomy, pathophysiology of pain, pharmacokinetic of pain drugs and of new device/therapies available. PMID- 22095107 TI - Ventilatory assist: if it gets going, how to know when to stop it? PMID- 22095109 TI - The Bonfils fiberscope: a clinical evaluation of its learning curve and efficacy in difficult airway management. AB - BACKGROUND: This study evaluated the use of the Bonfils fiberscope by analyzing its learning curve, efficacy and safety during airway management. METHODS: This was a prospective observational study where five anesthetists, with differing levels of experience, were asked to use the Bonfils rigid fiberscope (Karl Storz) for a six-month period. They used the scope when performing endotracheal intubations in patients undergoing general anesthesia. The patients were excluded if various clinical indicators predicted that they might be difficult to intubate. The patient's head was kept in the neutral position to simulate the intubation of a trauma patient. Direct laryngoscopy with a Macintosh blade was performed to assign a Cormack and Lehane grade prior to attempting laryngoscopy with the Bonfils fiberscope. After intubating the patient with the Bonfils fiberscope, intubation time and any complications or failures noted after the procedure were recorded. RESULTS: The study included 216 patients, three of which were failed intubations. No complications occurred during the study period. The median intubation time was 21.4 s. The learning curve improved significantly after 20 intubations (P<0.05) and was affected by the operator's experience and aptitude with endoscopic viewing. Seventeen patients were deemed to have "unpredicted" difficult airways: 15 subjects with a Cormack grade 3 (6.9%) and two subjects with a Cormack 4 (0.9%). Median time to intubation in subjects with a Cormack <3 was 16 s (95% CI=10-29 s), and in subjects with a Cormack >=3, it was 15 s (CI 95%=15-18 s) with P=0.703. CONCLUSION: The Bonfils fiberscope is an efficient, easy to use and safe device for endotracheal intubation. PMID- 22095108 TI - Inhibition of somatosensory evoked potentials during spinal cord stimulation and its possible role in the comprehension of antalgic mechanisms of neurostimulation for neuropathic pain. AB - BACKGROUND: Spinal cord stimulation (SCS) has been widely used for pain relief of patients with neuropathic chronic pain, frequently with only partial efficacy. Further advancements probably need a better understanding of SCS mechanisms, yet largely unknown. Aims of this paper were to answer the question if the lumbar SCS inhibits the tibial nerve somatosensory evoked potentials (SEPs) and to discuss the role of lemniscal afferents modulation in the antalgic mechanism of SCS. METHODS: Ten consecutive patients successfully treated with implanted SCS devices for chronic pain in the lower limbs (four males, six females, age range 42-72 years) were enrolled. All the patients had an implanted system with an epidural lead connected to a pulse generator. The vertebral level ranged from T9 to T12. The cortical SEPs complex P39-N50-P60 was recorded at the basal (T0) evaluation, during the stimulation (T1) and immediately after the stimulation (T2). RESULTS: In two of ten patients (20%) the complex P39-N50-P60 became unrelievable at the T1 control (stimulator on). In the remaining eight patients statistical analysis showed a significant reduction of the P39/N50 amplitude at T1 recording. In all patients considered, T0 and T2 recordings were not significantly different, suggesting a fast recovery of the SCS effect on SEPs. CONCLUSION: The results obtained in the present study show an inhibitory effect of SCS on SEPs and support the hypothesis that in some forms of neuropathic pain the antalgic effect of SCS could be attributed to the collision of action potentials travelling in opposite direction on peripheral large diameter fibres. PMID- 22095110 TI - Review of postpartum contraceptive practices at Chiang Mai University Hospital: implications for improving quality of service. AB - OBJECTIVE: To evaluate the acceptance rate and patterns of contraceptive use among postpartum women. SUBJECTS AND METHODS: The records of 1,009 postpartum women attending the Family Planning Clinic at Chiang Mai University Hospital, Thailand, during January to December 2009 were reviewed. RESULTS: Mean age was 28.2 +/- 5.7 years (range 15-48). Almost all 920 women (91.2%) practiced breastfeeding. The acceptance rate of contraception was 97.6%. The types of contraceptive used were: depot medroxyprogesterone acetate, 387 (38.4%); progestin-only pills, 262 (26.0%); tubal resection, 201 (19.9%); male condom, 78 (7.7%); oral combined pills, 49 (4.9%); intrauterine device, 5 (0.5%); implant, 3 (0.3%). Among women undergoing tubal resection, 29 (14.4%) were <=24 years of age. Significant independent predictors for using long-acting reversible contraception were young age and little or no formal education. CONCLUSION: The acceptance rate of contraception in this study was high. However, the following issues need to be evaluated: compliance of women using progestin-only pills, awareness of long-acting reversible contraception as an alternative option in women considering sterilization, and interventions to promote the use of intrauterine devices and implants. PMID- 22095111 TI - 1,2-Distanna-closo-dodecaborate--a rare example of a 1,2-distannylene ligand in transition metal chemistry. AB - The coordination chemistry of the novel bidentate tin ligand 1,2-distanna-closo dodecaborate is illustrated for the first time by reactions with molybdenum, platinum and gold metal complexes. Up to three clusters coordinate two metal centers in close proximity. For all these metal complexes the typical MU-bridging coordination mode was observed exclusively. Furthermore, two cluster anions react with dichloromethane via substitution of the chloride ions. The carbon functionalized tin cluster [Et(4)N](2)[CH(2)(Sn(2)B(10)H(10))(2)] and the coordination complexes [Et(3)NMe](6)[Mo(2)(CO)(6)(Sn(2)B(10)H(10))(3)], [Et(3)NMe](2)[{HPt(PEt(3))(2)(Sn(2)B(10)H(10))}(2)], [Et(4)N](2)[{HPt(PPh(3))(2)(Sn(2)B(10)H(10))}(2)] and [{(TP)Au}(2)(Sn(2)B(10)H(10))] (TP = PhP(o-Ph(2)PC(6)H(4))(2)) are fully characterized by multinuclear NMR spectroscopy, elemental analyses and crystal structure analyses. PMID- 22095112 TI - Concordance of the recently published body adiposity index with measured body fat percent in European-American adults. AB - The body adiposity index (BAI; hip circumference (cm)/height (m)(1.5) - 18) has recently been shown to demonstrate a stronger correlation with percentage body fat (%fat) than that between the BMI and %fat in Mexican-American adults. Here, we compare the concordance between %fat from dual-energy X-ray absorptiometry (DXA) and BAI, and between %fat and BMI, in European-American adults (n = 623). Agreement between BAI, BMI, and %fat was assessed using Lin's concordance coefficients (rho(c)), where values <0.90 are considered poor. In the sample as a whole, the agreement between BAI and %fat (rho(c) = 0.752) was far better than that between BMI and %fat (rho(c) = 0.445) but was nonetheless relatively poor. There were large mean differences in %fat between the BAI and DXA %fat, particularly at lower levels of adiposity (<20%), and further the BAI overestimated %fat in males and underestimated %fat in females. Optimizing the BAI formula for our sample only marginally improved performance. Results of the present study show that BAI provides a better indicator of adiposity in European American adults than does BMI, but does not provide valid estimates of %fat, particularly at lower levels of body fatness. Further research is warranted to investigate the predictive ability of BAI for various health outcomes. PMID- 22095113 TI - A new method for body fat evaluation, body adiposity index, is useful in women with familial partial lipodystrophy. AB - BMI is a widely used method to evaluate adiposity. However, it has several limitations, particularly an inability to differentiate lean from fat mass. A new method, body adiposity index (BAI), has been recently proposed as a new measurement capable to determine fat excess better than BMI. The aim of this study was to investigate BAI as a mean to evaluate adiposity in a group of women with familial partial lipodystrophy (FPLD) and compare it with BMI. Thirteen women with FLPD Dunnigan type (FPLD2) and 13 healthy volunteers matched by age and BMI were studied. Body fat content and distribution were analyzed by dual X ray absorptiometry (DXA). Plasma leptin was also measured. BAI was significantly lower in FPLD2 in comparison to control group (24.6 +/- 1.5 vs. 30.4 +/- 4.3; P < 0.001) and presented a more significant correlation with total fat (%) (r = 0.71; P < 0.001) and fat Mass (g) (r = 0.80; P < 0.001) than BMI (r = 0.27; P = 0.17 for total fat and r = 0.52; P = 0.006 for fat mass). There was a correlation between leptin and BAI (r = 0.57; P = 0.01), [corrected] but not between leptin and BMI. In conclusion, BAI was able to catch differences in adiposity in a sample of FPLD2 patients. It also correlated better with leptin levels than BMI. Therefore, we provide further evidence that BAI may become a more reliable indicator of fat mass content than the currently available measurements. PMID- 22095114 TI - SDCCAG8 obesity alleles and reduced weight loss after a lifestyle intervention in overweight children and adolescents. AB - Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m(2), mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10(-6)). However, our results could not be confirmed in 626 obese adults undertaking a hypoenergetic diet intervention. PMID- 22095115 TI - Viscous dietary fiber reduces adiposity and plasma leptin and increases muscle expression of fat oxidation genes in rats. AB - Dietary interventions that reduce accumulation of body fat are of great interest. Consumption of viscous dietary fibers cause well-known positive metabolic effects, such as reductions in the postprandial glucose and insulin concentrations. However, their effect on body composition and fuel utilization has not been previously studied. To examine this, rats were fed a viscous nonfermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), for 6 weeks. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and fat pad weight. Plasma adipokines, AMP kinase activation, and enzyme and mRNA analysis of key regulators of energetics in liver and soleus muscle were measured. The HPMC diet significantly lowered percent body fat mass and increased percent lean body mass, compared to a cellulose-containing diet (no viscosity). Fasting leptin was reduced 42% and resistin 28% in the HPMC group compared to the cellulose group. Rats fed HPMC had greater activation of AMP kinase in liver and muscle and lower phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. mRNA expression in skeletal muscle was significantly increased for carnitine palmitoyltransferase 1B (CPT-1B), PPARgamma coactivator 1alpha, PPARdelta and uncoupling protein 3 (UCP3), as was citrate synthase (CS) activity, in the HPMC group relative to the cellulose group. These results indicate that viscous dietary fiber preserves lean body mass and reduces adiposity, possibly by increasing mitochondrial biogenesis and fatty acid oxidation in skeletal muscle, and thus represents a metabolic effect of viscous fiber not previously described. Thus, viscous dietary fiber may be a useful dietary component to assist in reduction of body fat. PMID- 22095116 TI - Mode of consumption plays a role in alleviating hunger and thirst. AB - While studying the effect of structure on satiety, effects of mode of consumption, additional water to drink, and thirst have been neglected. The objective was to assess effects of structure, mode of consumption of food, and additional drinking of water on fullness and thirst. In study 1, 20 subjects (BMI 22.5 +/- 0.5 kg/m(2); age 21.4 +/- 3 years) underwent consumption conditions; SEW: solids to eat + 750 ml water to drink; LEW: liquefied soup to eat including 500 ml water + 250 ml water separately to drink; LDW: the same as LEW but served as drinks; SE, LE, and LD: the same as previous but without water to drink. In study 2, a subset of subjects underwent consumption conditions: solid carbohydrate, solid protein, solid fat: the same as SEW, but for each macronutrient separately; liquefied carbohydrate, liquefied protein, liquefied fat: the same as LEW, but for each macronutrient separately. Appetite, insulin concentration, glucose concentration, and ghrelin concentration were measured. Eating, independent of structure, suppressed desire to eat more than drinking (P < 0.01). Drinking water separately vs. water consumption in the food suppressed thirst more (P < 0.001). Regarding protein, satiety was higher in the solid vs. liquefied condition, while blood parameters were not significantly different. Only after drinking a meal most subjects (80%) wanted to consume more of the same meal, in order to alleviate hunger (63%) or quench thirst (37%). We conclude that mode of consumption plays a role in alleviating hunger and thirst. Subjects required further consumption after drinking the meal, motivated by hunger or thirst, showing that drinking a meal causes confusion that may imply a risk of overconsumption. PMID- 22095118 TI - The structure of soluble fibrin oligomers. PMID- 22095117 TI - Serum iron and iron stores in non-anemic patients with fibromyalgia. AB - The aim of the study was to assess iron serum levels and markers of iron stores in non-anemic fibromyalgia (FM) patients and to evaluate their impact on the prevalence and clinical manifestations of FM patients. Eighty-four patients with primary FM and 87 controls were investigated. Demographic and clinical data were collected from all participants. All patients completed the fibromyalgia impact questionnaire (FIQ). Patients evaluated the effect of the disease on their daily activity (DA) and judged the severity (DS) of the disease on a 0-10 scale. Venous blood was tested for serum iron, transferrin, ferritin, and soluble transferrin receptors (sTfR). Iron deficiency was defined if any of the following were present: serum iron <40 MUg/dL, serum ferritin levels <10 ng/mL, or sTfR levels >28.1 nmol/L. Analysis at a cutoff level of serum ferritin levels <=30 ng/mL and sTfR/ferritin ratio was also performed. Hemoglobin, iron, transferrin, sTfR, ferritin levels, and sTfR/ferritin ratios did not differ between the groups. The mean FIQ score was 57.13 +/- 20.21 and the DA and DS scores were 6.79 +/- 2.97 and 6.74 +/- 3.09, respectively. No correlations were found between the parameters studied and the FIQ or its ten individual items. Thirty-eight controls (43.7%) and 23 FM patients (27.4%) had ferritin levels of <=30 (p < 0.04). Within the FM group, lower levels were associated with lower total FIQ score and FIQ subscale scores. Patients with FM do not have reduced serum levels of iron or surrogate markers of iron stores. At present, there is no evidence to support iron supplementation in the treatment of FM. PMID- 22095119 TI - Salicylic acid differently regulates the transcription intensity of the mitochondrial genes of Lupinus luteus L. PMID- 22095120 TI - Tris-2(hydroxyethyl) ammonium 2-methylphenoxyacetate as an activator of aorta intima acid lipase. PMID- 22095122 TI - Intranasal administration of insulin eliminates the deficit of long-term spatial memory in rats with neonatal diabetes mellitus. PMID- 22095121 TI - Mechanisms of interaction of electron transport proteins in photosynthetic membranes of cyanobacteria. PMID- 22095123 TI - Tris-2(hydroxyethyl) ammonium 2-methylphenoxyacetate as an inhibitor of synthesis of liver phospholipase A1. PMID- 22095124 TI - Identification and primary characterization of novel cytochrome CYP74B1 of flax (Linum usitatissimum). PMID- 22095125 TI - Novel protein haponin regulates cellular response to oxidative stress. PMID- 22095126 TI - Biocomposite scaffolds containing regenerated silk fibroin and nanohydroxyapatite for bone tissue regeneration. PMID- 22095128 TI - Temperature independence of the primary electron transfer reaction rate constants in photosynthetic bacterial reaction centers. PMID- 22095127 TI - Fluorescent nanodiamond bioconjugates on the base of barnase:barstar module. PMID- 22095129 TI - Pre-steady-state kinetics of interaction of wild-type and multiple drug-resistant HIV protease with first and second generation inhibitory drugs. PMID- 22095130 TI - Allogenic serum improves cold preservation of osteochondral allografts. AB - BACKGROUND: Although several types of culture medium have been used for preservation of osteochondral allografts, the viability of chondrocytes decreases with increasing storage duration. We previously showed the University of Wisconsin solution is more suitable for graft preservation than culture medium. QUESTIONS/PURPOSES: We determined whether the addition of allogenic serum to University of Wisconsin solution increases chondrocyte survival during prolonged storage of osteochondral allografts. METHODS: Osteochondral tissue samples harvested from the distal femora of rats were preserved in University of Wisconsin solution supplemented with 0%, 1%, 10%, and 50% allogenic serum at 4 degrees C for 14 days. Cell viability and chondrocyte degenerative changes of the samples then were assessed using a tetrazolium assay and histologic methods. We also evaluated time-dependent changes in cell viability and histologic findings of samples preserved for 7, 14, and 21 days in University of Wisconsin solution supplemented with or without 10% allogenic serum. RESULTS: After 14 days of preservation, osteochondral tissue samples maintained in University of Wisconsin solution containing 10% or greater allogenic serum exhibited the highest cell viability and lowest degenerative changes in chondrocytes. In the evaluation of time-dependent changes, we found the chondrocyte degenerative changes were greater in cartilage preserved in University of Wisconsin solution alone than in University of Wisconsin solution containing 10% allogenic serum after day 7 or later. CONCLUSIONS: Our results suggest the addition of 10% allogenic serum to University of Wisconsin solution enhances viability of osteochondral tissue samples. CLINICAL RELEVANCE: The use of allogenic serum-supplemented University of Wisconsin solution is expected to prolong the duration of osteochondral allograft storage and result in higher-quality grafts. PMID- 22095131 TI - Intraarticular abnormalities in overhead athletes are variable. AB - BACKGROUND: The cause of shoulder pain and dysfunction in the overhead athlete can be variable. Several studies illustrate the wide variety of lesions seen at the time of arthroscopy in overhead athletes who require surgery but it is unclear whether these differ by sport. QUESTIONS/PURPOSES: We examined overhead athletes with shoulder dysfunction to determine (1) the range of arthroscopically visualized shoulder abnormalities with specific attention to the posterosuperior glenohumeral joint and the rotator cuff; and (2) the relationship of sport type to these abnormalities. METHODS: We reviewed our institution's database for professional and collegiate athletes in overhead sports who, from 1996 through 2010, had diagnostic shoulder arthroscopy for insidious, nontraumatic, persistent pain and inability to participate in their sport. A descriptive analysis of the arthroscopic findings from 51 consecutive patients (33 males, 18 females; mean age, 25 years; range, 15-59 years) was done. We analyzed the arthroscopic findings with respect to sport using analysis of variance and Fisher's exact test. RESULTS: There was a wide range of superior labrum, posterosuperior glenoid, and rotator cuff abnormalities. Overall, the most frequent abnormalities were posterosuperior glenohumeral joint changes. Swimmers had fewer intraarticular abnormalities than baseball players. CONCLUSIONS: We found a wide spectrum of intraarticular abnormalities in the shoulder of overhead athletes with shoulder pain requiring surgery. Additional study is needed to determine whether these abnormalities or combinations relate to specific athletic movements. LEVEL OF EVIDENCE: Level IV, retrospective case series. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22095133 TI - Sorafenib increases endoplasmic reticulum (ER) stress in concert with vorinostat. PMID- 22095132 TI - ATP binding cassette transporter G1 (ABCG1) is an intracellular sterol transporter. AB - Four members of the mammalian ATP binding cassette (ABC) transporter G subfamily are thought to be involved in transmembrane (TM) transport of sterols. The residues responsible for this transport are unknown. The mechanism of action of ABCG1 is controversial and it has been proposed to act at the plasma membrane to facilitate the efflux of cellular sterols to exogenous high-density lipoprotein (HDL). Here we show that ABCG1 function is dependent on localization to intracellular endosomes. Importantly, localization to the endosome pathway distinguishes ABCG1 and/or ABCG4 from all other mammalian members of this superfamily, including other sterol transporters. We have identified critical residues within the TM domains of ABCG1 that are both essential for sterol transport and conserved in some other members of the ABCG subfamily and/or the insulin-induced gene 2 (INSIG-2). Our conclusions are based on studies in which (i) biotinylation of peritoneal macrophages showed that endogenous ABCG1 is intracellular and undetectable at the cell surface, (ii) a chimeric protein containing the TM of ABCG1 and the cytoplasmic domains of the nonsterol transporter ABCG2 is both targeted to endosomes and functional, and (iii) ABCG1 colocalizes with multiple proteins that mark late endosomes and recycling endosomes. Mutagenesis studies identify critical residues in the TM domains that are important for ABCG1 to alter sterol efflux, induce sterol regulatory element binding protein-2 (SREBP-2) processing, and selectively attenuate the oxysterol mediated repression of SREBP-2 processing. Our data demonstrate that ABCG1 is an intracellular sterol transporter that localizes to endocytic vesicles to facilitate the redistribution of specific intracellular sterols away from the endoplasmic reticulum (ER). PMID- 22095134 TI - Antibiotic resistance and extended-spectrum beta-lactamases in isolated bacteria from seawater of Algiers beaches (Algeria). AB - The aim of the study was to evaluate bacterial antibiotic resistance in seawater from four beaches in Algiers. The most significant resistance rates were observed for amoxicillin and ticarcillin, whereas they were relatively low for ceftazidime, cefotaxime and imipenem. According to sampling sites, the highest resistance rates were recorded for 2 sites subjected to chemical and microbiological inputs (amoxicillin, 43% and 52%; ticarcillin, 19.6% and 47.7%), and for 2 sites relatively preserved from anthropogenic influence, resistance rates were lowest (amoxicillin, 1.5% and 16%; ticarcillin, 0.8% and 2.6%). Thirty four bacteria resistant to imipenem (n=14) or cefotaxime (n=20) were identified as Pseudomonas aeruginosa (n=15), Pseudomonas fluorescens (7), Stenotrophomonas maltophilia (4), Burkholderia cepacia (2), Bordetella sp. (1), Pantoea sp. (1), Acinetobacter baumannii (1), Chryseomonas luteola (1), Ochrobactrum anthropi (1) and Escherichia coli (1). Screening for extended spectrum beta-lactamase showed the presence of CTX-M-15 beta-lactamase in the E. coli isolate, and the encoding gene was transferable in association with the IncI1 plasmid of about 50 kbp. Insertion sequence ISEcp1B was located upstream of the CTX-M-15 gene. This work showed a significant level of resistance to antibiotics, mainly among environmental saprophytic bacteria. Transmissible CTX-M-15 was detected in E. coli; this may mean that contamination of the environment by resistant bacteria may cause the spread of resistance genes. PMID- 22095135 TI - AKT signaling pathway activated by HIN-1 methylation in non-small cell lung cancer. AB - The purpose of this study is to determine the epigenetic changes and function of High in Normal-1 (HIN-1) in non-small cell lung cancer (NSCLC). HIN-1 expression was examined by semiquantitative RT-PCR before and after 5-aza-2'-deoxycytidine (5-aza) treatment in NSCLC cell lines. Promoter methylation status of HIN-1 was tested by methylation-specific PCR (MSP). Effect of forced expression of HIN-1 on different key molecules of AKT signaling pathway was tested by Western Blot analysis in H157 and H23 cell lines. Promoter methylations are inversely correlated with expression of HIN-1 in eight (H23, H157, 95D, H1299, H358, H1752, H460, A549) of ten NSCLC cell lines and re-expression was observed by 5-aza treatment. We then tested promoter methylation of HIN-1 in primary NSCLC tissues. Methylation was detected in 73 out of 152 (48%) NSCLC cases. Forced expression of HIN-1 in NSCLC cell lines inhibited colony formation and induce apoptosis. Furthermore, overexpression of HIN-1 reduces the expression of phosphorated-AKT (p-AKT), c-myc, Bcl-2 and cyclinD1 while Bax was increased. Our data suggest that HIN-1 is a potential tumor suppressor gene in NSCLC, silenced by promoter hypermethylation and negatively regulate AKT signaling pathway. PMID- 22095136 TI - Thromboprophylaxis in patients older than 75 years or with moderate renal impairment undergoing knee or hip replacement surgery [corrected]. AB - PURPOSE: Prospective, double-blind studies in orthopaedic patients have been conducted using the direct thrombin inhibitor dabigatran etexilate (hereafter referred to as dabigatran), with two doses investigated and approved for adults (220 mg and 150 mg once daily) to prevent venous thromboembolism (VTE). The European Medicines Agency decided that in major joint orthopaedic surgery, the lower dose should be used in elderly patients (aged over 75 years) and those with reduced renal function (creatinine clearance between 30 and 50 ml/min). Our objective was to understand the efficacy and bleeding data for the lower dose in this subpopulation. METHODS: We extracted and analysed data from the elderly or from moderately renally impaired patients (n 632 of = 5,539) from the orthopaedic clinical development programme of dabigatran. RESULTS: Dabigatran 150 mg once daily was as effective as the standard European enoxaparin regimen, with numerically fewer major bleeding events. Rates of major VTE were 4.3% vs 6.4% of patients, respectively. Major bleeding events occurred in four (1.3%) vs 11 (3.3%), which shows a trend towards lower bleeding with dabigatran 150 mg [odds ratio (OR) 0.40; 95% confidence interval (CI) 0.13-1.25; p = 0.110]. Mean volume of blood loss was 395 vs 417 ml, and transfused units were 2.4 vs 2.5, respectively. Other safety parameters, including the incidence of wound infections and complications, were similar for 150 mg once daily dabigatran and enoxaparin. CONCLUSION: For patients at higher risk of bleeding, dabigatran 150 mg once daily is as effective as enoxaparin following major orthopaedic surgery and is associated with a favourable bleeding rate. PMID- 22095137 TI - Geometrical values of the normal and arthritic hip and knee detected with the EOS imaging system. AB - PURPOSE: EOS 2D/3D is an integrated, low-dose orthopedic digital radioimaging solution, which, due to its groundbreaking properties, has recently shown an increasing application in scoliosis surgery. Its integrated sterEOS 3D software allows creation of patient-specific three-dimensional (3D) lower limb models, and can produce geometrical parameters in 3D. Currently there are a limited number of reports on EOS for lower limb applications. METHODS: Three-dimensional reconstructions of 256 hip and knee joints of 128 healthy subjects, as well as 53 hips and 46 knees of 69 patients with hip or knee arthritis, were evaluated based on orthogonal EOS two-dimensional (2D) images. Measurements for hips included femur and tibia length, total length of the extremity, femoral antetorsion and offset, femoral neck length, neck-shaft and hip-knee-shaft (HKS) angles. Lower limb alignment in both frontal and sagittal planes were determined in normal and arthritic knees. Values were compared with those obtained by standard methods published by others. RESULTS: Normal hip and knee geometrical parameters were found in our healthy subjects. In osteoarthritic cases, values for neck-shaft angle, femoral antetorsion, femur length and total length of the extremity were shown to decrease non-significantly. Evaluation of lower limb alignment in healthy and arthritic knees showed normal values in healthy subjects apart from three cases with an average six degrees varus. Arthritic knees were most frequently found to have a varus angulation, with the exception of 11 cases with normal or valgus alignment. CONCLUSION: EOS 2D/3D with its sterEOS 3D reconstruction is useful for a comprehensive 3D examination of the lower limb. In the near future it may be suitable for daily routine diagnostics of orthopedic lower limb deformities as a primary examination method. PMID- 22095138 TI - Hyaluronan receptors in the human ocular surface: a descriptive and comparative study of RHAMM and CD44 in tissues, cell lines and freshly collected samples. AB - The purpose of this study was to demonstrate the presence of the receptor for hyaluronan-mediated motility (RHAMM) in human conjunctival epithelium and in two widely used cell lines from human corneal (HCE) and conjunctival (IOBA-NHC) epithelia. We compared the distribution of RHAMM proteins and mRNAs in human ocular surface tissues (corneal, limbal and conjunctival), HCE and IOBA-NHC cell lines, and corneal and conjunctival epithelia primary samples from healthy donors with the previously identified hyaluronan receptor CD44. We also aimed to determine if soluble CD44 (sCD44) was present in human tears, as it could have a role in the interaction of the tear fluid with hyaluronan. Protein expression was evaluated by Western blots and immunofluorescence microscopy. mRNA expression was evaluated by RT-PCR and Q-PCR. sCD44 was analyzed by ELISA in culture supernatants and in human tears. We describe the expression of RHAMM in human healthy conjunctiva and in HCE and IOBA-NHC cells at both protein and mRNA levels, and the presence of sCD44 in human tears. Furthermore, we detected CD44 and sCD44 expression variations in in vitro inflammatory conditions. This study also focused on the necessary caution with which the conclusions extracted from cell lines should be made, and in the great value of using primary samples as often as possible. PMID- 22095139 TI - Adhesions after laparoscopic and open ileal pouch-anal anastomosis surgery for ulcerative colitis. AB - BACKGROUND: Emerging evidence suggests that a laparoscopic approach to colorectal procedures generates fewer adhesions. Even though laparoscopic ileal pouch-anal anastomosis (IPAA) is a lengthy procedure, the prospect of fewer adhesions may justify this approach. The aim of this study was to assess abdominal and adnexal adhesion formation following laparoscopic versus open IPAA in patients with ulcerative colitis. METHODS: A diagnostic laparoscopy was performed at time of ileostomy closure. All abdominal quadrants and the pelvis were video recorded systematically and graded offline. The incisional adhesion score (IAS; range 0-6) and total abdominal adhesion score (TAS; range 0-10) were calculated, based on the grade and extent of adhesions. Adnexal adhesions were classified by the American Fertility Society (AFS) adhesion score. RESULTS: A total of 43 patients consented to participate, of whom 40 could be included in the study (laparoscopic 28, open 12). Median age was 38 (range 20-61) years. There was no difference in age, sex, body mass index, American Society of Anesthesiologists grade and time to ileostomy closure between groups. The IAS was significantly lower after laparoscopic IPAA than following an open procedure: median (range) 0 (0-5) versus 4 (2-6) respectively (P = 0.004). The TAS was also significantly lower in the laparoscopic group: 2 (0-6) versus 8 (2-10) (P = 0.002). Applying the AFS score, women undergoing laparoscopic IPAA had a significantly lower mean(s.d.) prognostic classification score than those in the open group: 5.2(3.7) versus 20.0(5.6) (P = 0.023). CONCLUSION: Laparoscopic IPAA was associated with significantly fewer incisional, abdominal and adnexal adhesions in comparison with open IPAA. PMID- 22095140 TI - In situ synthesis of porous silica nanoparticles for covalent immobilization of enzymes. AB - A simple method is used to covalently encapsulate enzymes in silica nanoparticles. The encapsulation is highlighted by the high enzyme loading and porous channels that provide efficient diffusion for small substrate and product molecules while preventing protease degradation. PMID- 22095143 TI - Alcohol consumption and prostate cancer risk: a meta-analysis of the dose-risk relation. AB - Inconsistent results on the relationship between alcohol drinking and prostate cancer have been found. In order to provide a definite quantification of the dose risk relation, we investigated the risk of prostate cancer at different levels of alcohol consumption, by conducting a meta-analysis of epidemiological studies. We performed a literature search using PubMed of all case-control and cohort studies published as original articles in English up to December 2010. We identified 50 case-control and 22 cohort studies, including a total of 52 899 prostate cancer cases. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates. We performed a dose-risk analysis using nonlinear random-effects meta-regression models. The overall relative risk for any alcohol drinking compared with non/occasional drinking was 1.06 [95% confidence interval (CI), 1.01-1.10]. The relative risks were 1.05 (95% CI, 1.02-1.08), 1.06 (95% CI, 1.01-1.11), and 1.08 (95% CI, 0.97-1.20) for light (<=1 drink/day), moderate (>1 to <4 drinks/day), and heavy alcohol drinking (>=4 drinks/day), respectively. This comprehensive meta-analysis provided no evidence of a material association between alcohol drinking and prostate cancer, even at high doses. PMID- 22095142 TI - Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot prospective study. AB - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) patients suffer from significant morbidity and diminished life quality. The plant cannabis is beneficial in various gastrointestinal diseases, stimulating appetite and causing weight gain. Our aims were to assess whether treatment with inhaled cannabis improves quality of life, disease activity and promotes weight gain in these patients. METHODS: Patients with long-standing IBD who were prescribed cannabis treatment were included. Two quality of life questionnaires and disease activity indexes were performed, and patient's body weight was measured before cannabis initiation and after 3 months' treatment. RESULTS: Thirteen patients were included. After 3 months' treatment, patients reported improvement in general health perception (p = 0.001), social functioning (p = 0.0002), ability to work (p = 0.0005), physical pain (p = 0.004) and depression (p = 0.007). A schematic scale of health perception showed an improved score from 4.1 +/- 1.43 to 7 +/- 1.42 (p = 0.0002). Patients had a weight gain of 4.3 +/- 2 kg during treatment (range 2-8; p = 0.0002) and an average rise in BMI of 1.4 +/- 0.61 (range 0.8 2.7; p = 0.002). The average Harvey-Bradshaw index was reduced from 11.36 +/- 3.17 to 5.72 +/- 2.68 (p = 0.001). CONCLUSIONS: Three months' treatment with inhaled cannabis improves quality of life measurements, disease activity index, and causes weight gain and rise in BMI in long-standing IBD patients. PMID- 22095146 TI - Space-time decoupling in the branching process in the mutant etoile of the filamentous brown alga Ectocarpus siliculosus. AB - Ectocarpus siliculosus is being developed as a model organism for brown algal genetics and genomics. Brown algae are phylogenetically distant from the other multicellular phyla (green lineage, red algae, fungi and metazoan) and therefore might offer the opportunity to study novel and alternative developmental processes that lead to the establishment of multicellularity. E. siliculosus develops as uniseriate filaments, thereby displaying one of the simplest architectures among multicellular organisms. The young sporophyte grows as a primary filament and then branching occurs, preferentially at the center of the filament. We recently described the first morphogenetic mutant etoile (etl) in a brown alga, produced by UVB mutagenesis in E. siliculosus. We showed that a single recessive mutation was responsible for a defect in both cell differentiation and the very early branching pattern (first and second branch emergences). Here, we supplement this study by reporting the branching defects observed subsequently, i.e. for the later stages corresponding to the emergence of up to the first six secondary filaments, and we show that the branching process is composed of at least two distinct components: time and position. PMID- 22095147 TI - Trichomes as dangerous lollipops: do lizards also use caterpillar body and frass odor to optimize their foraging? AB - When attacked by herbivores, plants produce toxic secondary metabolites that function as direct defenses, as well as indirect defenses that attract and reward predators of the offending herbivores. These indirect defenses include both nutritive rewards such as extra floral nectar, as well as informational rewards, such as the production and release of volatile compounds that betray the location of feeding herbivores to predators. Herbivory of Nicotiana attenuata by the tobacco hornworm (Manduca larvae) alters the volatile profiles of both the plant and larval headspace. Herbivory-elicited specific changes in the volatile profiles are detected by arthropod predators of Manduca larvae. The known predators that perceive volatile cues induced by Manduca herbivory of N. attenuata are insects that target Manduca at early developmental stages, when the larvae are still small; large, late-instar larvae may have outgrown these predation risks. However, here we offer evidence that branched chain aliphatic acids derived from the digestion of plant O-acyl sugars from trichomes may betray Manduca larvae to lizard predators during late developmental stages as well. PMID- 22095148 TI - Abscisic acid perception and signaling transduction in strawberry: a model for non-climacteric fruit ripening. AB - On basis of fruit differential respiration and ethylene effects, climacteric and non-climacteric fruits have been classically defined. Over the past decades, the molecular mechanisms of climacteric fruit ripening were abundantly described and found to focus on ethylene perception and signaling transduction. In contrast, until our most recent breakthroughs, much progress has been made toward understanding the signaling perception and transduction mechanisms for abscisic acid (ABA) in strawberry, a model for non-climacteric fruit ripening. Our reports not only have provided several lines of strong evidences for ABA-regulated ripening of strawberry fruit, but also have demonstrated that homology proteins of Arabidopsis ABA receptors, including PYR/PYL/RCAR and ABAR/CHLH, act as positive regulators of ripening in response to ABA. These receptors also trigger a set of ABA downstream signaling components, and determine significant changes in the expression levels of both sugar and pigment metabolism-related genes that are closely associated with ripening. Soluble sugars, especially sucrose, may act as a signal molecular to trigger ABA accumulation through an enzymatic action of 9-cis-epoxycarotenoid dioxygenase 1 (FaNCED1). This mini-review offers an overview of these processes and also outlines the possible, molecular mechanisms for ABA in the regulation of strawberry fruit ripening through the ABA receptors. PMID- 22095149 TI - Optimal web investment in sub-optimal foraging conditions. AB - Orb web spiders sit at the centre of their approximately circular webs when waiting for prey and so face many of the same challenges as central-place foragers. Prey value decreases with distance from the hub as a function of prey escape time. The further from the hub that prey are intercepted, the longer it takes a spider to reach them and the greater chance they have of escaping. Several species of orb web spiders build vertically elongated ladder-like orb webs against tree trunks, rather than circular orb webs in the open. As ladder web spiders invest disproportionately more web area further from the hub, it is expected they will experience reduced prey gain per unit area of web investment compared to spiders that build circular webs. We developed a model to investigate how building webs in the space-limited microhabitat on tree trunks influences the optimal size, shape and net prey gain of arboricolous ladder webs. The model suggests that as horizontal space becomes more limited, optimal web shape becomes more elongated, and optimal web area decreases. This change in web geometry results in decreased net prey gain compared to webs built without space constraints. However, when space is limited, spiders can achieve higher net prey gain compared to building typical circular webs in the same limited space. Our model shows how spiders optimise web investment in sub-optimal conditions and can be used to understand foraging investment trade-offs in other central-place foragers faced with constrained foraging arenas. PMID- 22095150 TI - [MR microscopy of the human eye]. AB - Ultra-high-field MR microscopy is a novel, non-invasive imaging technique to explore the strcutures of the human eye without optical distorsions. This review aims to provide an insight into the technique of the method. The normal MR microscopic anatomy of the human eye with correlations to histology is demonstrated. The use of MR microscopy in ther experimental ophthalmological setting is discussed. PMID- 22095151 TI - [Long-term outcome after penetrating keratoplasty for bullous keratopathy - influence of preoperative visual acuity on final outcome]. AB - PURPOSE: The aim of this study was to analyse the long-term functional results of penetrating keratoplasty for pseudophacic bullous keratopathy and Fuchs endothelial dystrophy and to analyse the potential influence of the preoperative visual acuity on the final outcome. PATIENTS AND METHODS: This retrospective study describes the postoperative results of 413 patients. 154 of them with bullous keratopathy and 259 patients with Fuchs dystrophy. All received penetrating excimer laser keratoplasty (PK).The results include the examination of the patients 1 / 3 / 5 / 8 / > 9 years postoperatively. For analysis the patients were divided in two groups: group I includes patients with a visual acuity <= 0.1 and group II with a visual acuity > 0.1. The trephination was performed using a 193 nm excimer laser. The transplanted cornea was fixed by using a double running cross-stitch suture. The outcome measures included best corrected visual acuity (CCV), keratometric equivalent (KEQ), keratometric astigmatism (AST), spherical equivalent (SEQ), refractive cylinder (CYL), best corrected visual acuity (BCVA), surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity (PVA), pachymetry (PAC), endothelial cell count (ECC), intraocular tension (TEN), topographic equivalent (T-EQ) and topographic astigmatism (T-AST). RESULTS: 5 / 8 years postoperatively CCV was 0.55 / 0.58; KEQ was 43.75 / 45.64 D; SEQ - 0.88 /- 1.88 D; AST was 3.91 / 4.41 D; CYL was 3.09 / 3.40 D; ECC was 1230 / 1080 cells/mm (2); TEN was 13.61 / 14.36 mmHg; PAC was 593.21 / 579.50 um; SRI was 1.08 / 0.89; SAI was 1.31 / 1.10; PVA was 0.77 / 0.83; T-EQ was 44.78 / 44.92 D and T-AST was 4.85 / 3.92 D. The outcome of patients with a preoperative visual acuity of <= 0.1 was significantly worse than the group with the visual acuity of > 0.1. CONCLUSION: This study shows that the long-term results after penetrating keratoplasty for pseudophacic bullous keratopathy and Fuchs endothelial dystrophy are good. Patients with preoperative visual acuity of <= 0.1 had worse final results. PMID- 22095152 TI - Clinical management of ESBL-producing Enterobacteriaceae: the insidious role of fluoroquinolones. AB - During a review of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in our Hospital, a huge number of inadequate antimicrobial therapies emerged. The aim of this study is to assess the factors related to such inadequacy. This retrospective analysis was performed on isolates reported by the microbiology laboratory. Medical records were analyzed to assess adequate treatment; inadequacy was evaluated as overall therapy, antibiotic choice, dosage and length of treatment. Linear regression and multivariate analysis were performed to assess any association. One hundred and fifty isolates were analyzed. They were more commonly isolated from urinary samples and from patients admitted to the Internal Medicine Department; E. coli was the most commonly isolated pathogen. The rate of inadequacy was 60.67%. Fluoroquinolones seem to be the main class responsible. Ceftriaxone, teicoplanin, tigecycline and amoxicillin clavulanate are other antibiotics inadequately prescribed. Clinical management of these infections should be better tailored: the knowledge of pathogens should be implemented and the use of diagnostic tools, such as microbiology results, must be optimized. In particular, the prescription of each antibiotic course (and above all of regimens containing fluoroquinolones) should be performed not on a routine basis, but after careful assessment of each case. PMID- 22095153 TI - Sputum induction for the diagnosis of pulmonary tuberculosis: a systematic review and meta-analysis. AB - Sputum induction (SI) has been proposed as the optimal sample collection method for patients with paucibacillary tuberculosis (TB). Studies reporting the culture of Mycobacterium tuberculosis from SI were reviewed. A random-effects meta analysis of diagnostic yield (numerator M. tuberculosis SI culture-positive cases; denominator all culture-positive cases) was conducted. Diagnostic yields (95% confidence intervals, CIs) were displayed as Forest plots. Heterogeneity was evaluated using Chi-squared and I-squared tests and meta-regression analysis. Ninety publications were screened, 28 full-text papers reviewed, and 17 analyzed. Collectively, n=627 SI culture-positive cases among n=975 culture-confirmed TB cases were reported. The diagnostic yield of SI ranged from 35 to 95%. The pooled diagnostic yield was 74% (CI 65-81%), with significant heterogeneity (p<0.0001, I2=86%). There were no statistically significant differences in the yield between sub-groups defined by human immunodeficiency virus (HIV) prevalence or age. Univariate analysis demonstrated that the use of fiberoptic bronchoscopy (FOB) as the comparator method was associated with a 22% reduction (CI 2-42%) in the diagnostic yield of SI. However, after adjustment for confounding, the meta regression analysis showed that FOB usage (p=0.21) and saline concentration (p=0.31) were not independently associated with the diagnostic yield. SI will detect approximately three-quarters of M. tuberculosis culture-positive cases under study conditions. Significant heterogeneity in the diagnostic yield was not explained by HIV prevalence, age, or the use of FOB as the comparator method. The use of a particular nebulized saline concentration for SI cannot be recommended on the basis of this meta-regression analysis. PMID- 22095154 TI - Antiproliferative effect of SOCS-1 through the suppression of STAT3 and p38 MAPK activation in gastric cancer cells. AB - Inflammation is a crucial driving force in the development of gastric cancers (GCs). Accordingly, persistent activation of STAT3, a transcription factor pivotal in regulating both inflammation and oncogenesis, is often detected in GC, although its mechanism remains elusive. Suppressor of cytokine signaling-1 (SOCS 1) is a negative regulator of proinflammatory cytokine signaling and SOCS-1 gene methylation is frequently detected in various cancers including GC. However, the significance of SOCS-1 methylation in GC cells remains unexplored. Our study is undertaken to evaluate the role of SOCS-1 in GC cell proliferation and its effect on signaling pathways in GC cells. Among five GC cell lines, SOCS-1 gene was methylated in all cell lines and constitutive STAT3 phosphorylation with elevated endogenous IL-6 production was detected in two cell lines (NUGC-3 and AGS). Unexpectedly, anti-IL-6R antibody inhibited neither cell proliferation nor STAT3 phosphorylation in NUGC-3 and AGS. In contrast, enforced SOCS-1 expression by adenoviral vector (AdSOCS-1) markedly suppressed STAT3 phosphorylation and proliferation of NUGC-3 and AGS cells in vitro. Interestingly, the antiproliferative effect of SOCS-1 was attributable not only to the inhibition of STAT3 but also to that of p38 MAPK activity, and chemical inhibitors of JAK/STAT and p38 MAPK signaling effectively suppressed proliferation of these GC cells. Furthermore, treatment with AdSOCS-1 in vivo significantly suppressed GC proliferation in a xenograft model. These results suggest that SOCS-1 gene methylation is a critical step in the development of GC, and enforced expression of SOCS-1 may represent a novel therapeutic approach for the treatment of GC. PMID- 22095155 TI - Illness perception and knowledge with regard to prediabetes and type 2 diabetes: a pilot study of emergency department patients and staff. AB - BACKGROUND: We aimed to explore emergency department (ED) patients', doctors', and nurses' knowledge and illness perception with regard to prediabetes and type 2 diabetes mellitus (T2DM), and to determine whether patients' diabetes risk was associated with illness perception. METHODS: A cross-sectional survey of adult ED patients and clinicians was undertaken. Patients and clinicians were administered the 72-item Illness Perception Questionnaire-Revised, five researcher-generated questions with regard to the awareness of T2DM, and seven items with regard to the efficacy of lifestyle interventions. Patients were also administered the eight-item Type 2 Diabetes Risk Test. RESULTS: Of 127 patients and 29 ED clinicians recruited, only 30 (38/127) and 72% (21/29), respectively, reported having heard of prediabetes. Thirty-six percent of patients had an intermediate high risk of developing T2DM according to the Diabetes Risk Test. The risk of developing T2DM was weakly correlated (r<0.19) with all Illness Perception Questionnaire subscales. CONCLUSION: Knowledge of prediabetes is poor among ED patients and many are unaware that T2DM may be asymptomatic. Patients and clinicians perceived lifestyle factors to be causative for T2DM, but both perceived patients as having little control over the condition. The capacity of lifestyle modifications to alter the course of T2DM should be emphasized in future education programs. PMID- 22095156 TI - Amiodarone-induced thyrotoxicosis with thyroid papillary cancer in multinodular goiter: case report. AB - OBJECTIVE: To report a case of amiodarone-induced thyrotoxicosis (AIT) concomitant with thyroid cancer in multinodular goiter (MNG). CLINICAL PRESENTATION AND INTERVENTION: A 61-year-old man treated with amiodarone for 5 years presented with mild sweating. He was found to have AIT simultaneously with thyroid papillary cancer and MNG. Administration of amiodarone was stopped, and he was treated with methimazole for AIT. Five weeks after the initial treatment, thyroid function normalized. Total thyroidectomy was considered to enable use of amiodarone again. CONCLUSION: This case showed that thyrotoxicosis, MNG and amiodarone may contribute to thyroid carcinogenesis. Amiodarone should be carefully commenced in cases with MNG. PMID- 22095159 TI - A novel MOF with mesoporous cages for kinetic trapping of hydrogen. AB - A stable MOF, assigned PCN-105, with two types of mesoporous cages, has been prepared by using a new multidentate flexible ligand with amine functional groups, and PCN-105 exhibits a marked N(2), O(2), Ar and H(2) hysteretic behaviour. PMID- 22095157 TI - In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization. AB - Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Adelta-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers a realistic chance that this novel mechanism to inhibit afferent nerve sensitization may find its place in the sun and bring some merciful relief to the torment of persistent discomfort and pain. The development philosophy at Afferent is to conduct proof of concept patient studies and best identify target patient groups that may benefit from this new intervention. PMID- 22095158 TI - Measurement of purine release with microelectrode biosensors. AB - Purinergic signalling departs from traditional paradigms of neurotransmission in the variety of release mechanisms and routes of production of extracellular ATP and adenosine. Direct real-time measurements of these purinergic agents have been of great value in understanding the functional roles of this signalling system in a number of diverse contexts. Here, we review the methods for measuring purine release, introduce the concept of microelectrode biosensors for ATP and adenosine and explain how these have been used to provide new mechanistic insight in respiratory chemoreception, synaptic physiology, eye development and purine salvage. We finish by considering the association of purine release with pathological conditions and examine the possibilities that biosensors for purines may one day be a standard part of the clinical diagnostic tool chest. PMID- 22095160 TI - Inter-population comparisons of copper resistance and accumulation in the red seaweed, Gracilariopsis longissima. AB - Copper (Cu) resistance and accumulation of five populations of the red seaweed Gracilariopsis longissima collected from sites in south west England (Fal Estuary, Helford Estuary and Chesil Fleet) that differ in their degree of Cu contamination was assessed under controlled laboratory conditions, on two separate occasions (April and October). The effects of a range of Cu concentrations (0-250 MUg l(-1)) on relative growth rates was the same for all populations with reductions observable at concentrations as low as 12 MUg l(-1) and cessation of growth at 250 MUg l(-1). There was no significant difference in the calculated EC(50) values for the April and October samples, with means of 31.1 and 25.8 MUg l(-1), respectively. Over the range of concentrations used in this study, copper content increased linearly and the pattern of accumulation was the same for all populations at both time periods. From the linear regressions of the pooled data a concentration factor of 2.25 * 10(3) was calculated. These results imply that G. longissima has an innate tolerance to Cu and that populations have not evolved copper-tolerant ecotypes. In laboratory studies, accumulated Cu was released when transferred to 'clean' seawater with approximately 80% being lost after 8 days, with no significant difference between populations in their response. The results from a 30 days in situ transplantation experiment using two populations from the Fal Estuary provided further evidence for dynamic changes in Cu content in response to changes in Cu bioavailability. The findings in this study are discussed in the context of implications for seaweed biomonitoring. PMID- 22095161 TI - Response to "Traits and stress: keys to identify community effects of low levels of toxicants in test systems" by Liess and Beketov (2011). PMID- 22095163 TI - Protonolysis of [((i)PrO)TiMo5O18]3-: access to a family of TiMo5 Lindqvist type polyoxometalates. AB - The tetra-n-butylammonium (TBA) salts of [((i)PrO)TiMo(5)O(18)](3-) 1 and [((i)BuO)TiMo(5)O(18)](3-) 2 were prepared by hydrolysis of mixtures of (TBA)(2)[Mo(2)O(7)], (TBA)(4)alpha-[Mo(8)O(26)] and Ti(OR)(4) (R = (i)Pr or (i)Bu) in acetonitrile. Treatment of (TBA)(3)1 with alcohols ROH afforded primary and tertiary alkoxide derivatives [(RO)TiMo(5)O(18)](3-) (R = Me 3, (t)Bu 4), whilst aryloxides [(ArO)TiMo(5)O(18)](3-) were prepared by reacting 1 with phenols ArOH (Ar = C(6)H(4)Me-4 5, and C(6)H(4)CHO-2 6). Oxo-bridged [(MU O)(TiMo(5)O(18))(2)](6-)7 rather than the hydroxo derivative [(HO)TiMo(5)O(18)](3 ) was obtained upon hydrolysis of 1. X-Ray crystal structures of TBA salts of anions 3-7 show that titanium is six-coordinate in all cases, although titanium sites are disordered over two trans positions in 3. Mo-O bond length alternation is observed in the Mo(4)O(4) planes of 4 and 7 and in one of the two independent anions in the structure of 3. In solution, (17)O NMR spectra are consistent with the higher anionic charge compared to [Mo(6)O(19)](2-) and reveal an order of basicity for the anions [LM'Mo(5)O(18)](3-) associated with the ability of {LM'}(3+) to donate/withdraw electron density from {Mo(5)O(18)}(6-). Protonolysis reactions of 1 and 3 were slower than for tungstate analogues and the possibility of initial protonation at TiOM (M = Mo) rather than TiOR (M = W) in a proton assisted S(N)1 mechanism for ligand exchange in [(RO)TiM(5)O(18)](3-) is discussed. PMID- 22095162 TI - Physiological responses of Microcystis aeruginosa NIES-843 (cyanobacterium) under the stress of chitosan modified kaolinite (CMK) loading. AB - Flocculation with clays is a promising and environmentally friendly way to remove algal blooms. Physiological responses of Microcystis aeruginosa NIES-843 under the stress of chitosan modified kaolinite (CMK) loading were first reported in this paper. Compared with the control, the contents of chlorophyll a (Chl a) and carotenoids showed no significant difference at a CMK loading of 40 mg/l, but the phycocyanin content was significant lower than the control at this loading level. The contents of Chl a, carotenoids, phycocyanin and allophycocyanin were all significantly lower than the control at 80 and 160 mg/l CMK, and the leakage of phycobilins occurred at these two loading levels suggesting that flocculation with CMK could cause the damage of cellular membranes. The activities of extracellular alkaline phosphatase activity (E-APA), superoxide dismutase (SOD) and catalase (CAT) were all dramatically boosted under the stress of CMK loading. The changes of cellular dehydrogenase activity exhibited the same trends as of Chl a and carotenoids, and it decreased to the levels of lower than detectable limits on 12 and 8th day at a CMK loading of 80 and 160 mg/l, respectively. These results indicated that flocculation with CMK could cause cell mortality of M. aeruginosa. PMID- 22095164 TI - Laterality of spinocerebellar neurons in the chicken spinal cord. AB - The aim in this study is to elucidate the laterality of chicken spinocerebellar (SC) neurons that originate from the caudal cervical to caudal lumbosacral spinal cord. SC neurons in the spinal segment (SS) 17-20 consisted of a mixture of crossed and uncrossed axons. SC neurons in the more cranial and caudal SS than SS 17-20 (transitional zone) were generally uncrossed and crossed, respectively. In the transitional zone, SC neurons in spinal border cells and ventral border cells of the ventral horn changed dramatically from an uncrossed to a crossed type between SS 17 and SS 18. Chicken SC neurons are markedly different in laterality from mammalian SC neurons. PMID- 22095165 TI - Occurrence of C-terminal residue exclusion in peptide fragmentation by ESI and MALDI tandem mass spectrometry. AB - By screening a data set of 392 synthetic peptides MS/MS spectra, we found that a known C-terminal rearrangement was unexpectedly frequently occurring from monoprotonated molecular ions in both ESI and MALDI tandem mass spectrometry upon low and high energy collision activated dissociations with QqTOF and TOF/TOF mass analyzer configuration, respectively. Any residue localized at the C-terminal carboxylic acid end, even a basic one, was lost, provided that a basic amino acid such arginine and to a lesser extent histidine and lysine was present in the sequence leading to a fragment ion, usually depicted as (b(n-1) + H(2)O) ion, corresponding to a shortened non-scrambled peptide chain. Far from being an epiphenomenon, such a residue exclusion from the peptide chain C-terminal extremity gave a fragment ion that was the base peak of the MS/MS spectrum in certain cases. Within the frame of the mobile proton model, the ionizing proton being sequestered onto the basic amino acid side chain, it is known that the charge directed fragmentation mechanism involved the C-terminal carboxylic acid function forming an anhydride intermediate structure. The same mechanism was also demonstrated from cationized peptides. To confirm such assessment, we have prepared some of the peptides that displayed such C-terminal residue exclusion as a C-terminal backbone amide. As expected in this peptide amide series, the production of truncated chains was completely suppressed. Besides, multiply charged molecular ions of all peptides recorded in ESI mass spectrometry did not undergo such fragmentation validating that any mobile ionizing proton will prevent such a competitive C-terminal backbone rearrangement. Among all well known nondirect sequence fragment ions issued from non specific loss of neutral molecules (mainly H(2)O and NH(3)) and multiple backbone amide ruptures (b-type internal ions), the described C-terminal residue exclusion is highly identifiable giving raise to a single fragment ion in the high mass range of the MS/MS spectra. The mass difference between this signal and the protonated molecular ion corresponds to the mass of the C-terminal residue. It allowed a straightforward identification of the amino acid positioned at this extremity. It must be emphasized that a neutral residue loss can be misattributed to the formation of a y(m-1) ion, i.e., to the loss of the N-terminal residue following the a(1)-y(m-1) fragmentation channel. Extreme caution must be adopted when reading the direct sequence ion on the positive ion MS/MS spectra of singly charged peptides not to mix up the attribution of the N- and C-terminal amino acids. Although such peculiar fragmentation behavior is of obvious interest for de novo peptide sequencing, it can also be exploited in proteomics, especially for studies involving digestion protocols carried out with proteolytic enzymes other than trypsin (Lys-N, Glu-C, and Asp-N) that produce arginine-containing peptides. PMID- 22095166 TI - Differentiation of the stereochemistry and anomeric configuration for 1-3 linked disaccharides via tandem mass spectrometry and 18O-labeling. AB - Collision-induced dissociation (CID) of deprotonated hexose-containing disaccharides (m/z 341) with 1-2, 1-4, and 1-6 linkages yields product ions at m/z 221, which have been identified as glycosyl-glycolaldehyde anions. From disaccharides with these linkages, CID of m/z 221 ions produces distinct fragmentation patterns that enable the stereochemistries and anomeric configurations of the non-reducing sugar units to be determined. However, only trace quantities of m/z 221 ions can be generated for 1-3 linkages in Paul or linear ion traps, preventing further CID analysis. Here we demonstrate that high intensities of m/z 221 ions can be built up in the linear ion trap (Q3) from beam type CID of a series of 1-3 linked disaccharides conducted on a triple quadrupole/linear ion trap mass spectrometer. (18)O-labeling at the carbonyl position of the reducing sugar allowed mass-discrimination of the "sidedness" of dissociation events to either side of the glycosidic linkage. Under relatively low energy beam-type CID and ion trap CID, an m/z 223 product ion containing (18)O predominated. It was a structural isomer that fragmented quite differently than the glycosyl-glycolaldehydes and did not provide structural information about the non-reducing sugar. Under higher collision energy beam-type CID conditions, the formation of m/z 221 ions, which have the glycosyl-glycolaldehyde structures, were favored. Characteristic fragmentation patterns were observed for each m/z 221 ion from higher energy beam-type CID of 1-3 linked disaccharides and the stereochemistry of the non-reducing sugar, together with the anomeric configuration, were successfully identified both with and without (18)O-labeling of the reducing sugar carbonyl group. PMID- 22095167 TI - New evidence of the role of the hypoxia-regulated pathway in nucleus pulposus cell survival: comment on the article by Hiyama et al. PMID- 22095168 TI - Lessons from an incidental diagnosis of paroxysmal nocturnal haemoglobinuria. PMID- 22095169 TI - Detection of SET-NUP214 rearrangement using multiplex reverse transcriptase polymerase chain reaction (RT-PCR) in acute leukemias: a case report and literature review on a Korean case series. PMID- 22095170 TI - Complete disappearance of hemichorea-hemiballism due to hyperglycemia following acute ischemic stroke. PMID- 22095171 TI - SiO2 nanoparticles biocompatibility and their potential for gene delivery and silencing. AB - Despite the extensive use of silica nanoparticles (SiO(2)NPs) in many fields, the results about their potential toxicity are still controversial. In this work, we have performed a systematic in vitro study to assess the biological impact of SiO(2)NPs, by investigating 3 different sizes (25, 60 and 115 nm) and 2 surface charges (positive and negative) of the nanoparticles in 5 cell lines (3 in adherence and 2 in suspension). We analyzed the cellular uptake and distribution of the NPs along with their possible effects on cell viability, membrane integrity and generation of reactive oxygen species (ROS). Experimental results show that all the investigated SiO(2)NPs do not induce detectable cytotoxic effects (up to 2.5 nM concentration) in all cell lines, and that cellular uptake is mediated by an endocytic process strongly dependent on the particle size and independent of its original surface charge, due to protein corona effects. Once having assessed the biocompatibility of SiO(2)NPs, we have evaluated their potential in gene delivery, showing their ability to silence specific protein expression. The results of this work indicate that monodisperse and stable SiO(2)NPs are not toxic, revealing their promising potential in various biomedical applications. PMID- 22095172 TI - Stationarity stopping criterion for matching pursuit-framework and encephalographic illustration. AB - We present a new stopping criterion for the matching pursuit (MP) algorithm, based on evaluating stationarity of the residua of the consecutive MP iterations. The new stopping criterion is based on a model of a nonstationary signal, which assumes that the part of the signal that is of interest is nonstationary and contaminated by a weakly stationary noise. Mean- and variance-stationarity of the residua obtained from each step of MP is evaluated by means of dedicated statistical tests-the Kwiatkowski-Phillips-Schmidt-Shin (KPSS) test and the White test, respectively. We illustrate the proposed concept by an example in which we analyse magnetoencephalographic (MEG) data. PMID- 22095173 TI - Application of modern tests for stationarity to single-trial MEG data: transferring powerful statistical tools from econometrics to neuroscience. AB - Stationarity is a crucial yet rarely questioned assumption in the analysis of time series of magneto- (MEG) or electroencephalography (EEG). One key drawback of the commonly used tests for stationarity of encephalographic time series is the fact that conclusions on stationarity are only indirectly inferred either from the Gaussianity (e.g. the Shapiro-Wilk test or Kolmogorov-Smirnov test) or the randomness of the time series and the absence of trend using very simple time series models (e.g. the sign and trend tests by Bendat and Piersol). We present a novel approach to the analysis of the stationarity of MEG and EEG time series by applying modern statistical methods which were specifically developed in econometrics to verify the hypothesis that a time series is stationary. We report our findings of the application of three different tests of stationarity--the Kwiatkowski-Phillips-Schmidt-Schin (KPSS) test for trend or mean stationarity, the Phillips-Perron (PP) test for the presence of a unit root and the White test for homoscedasticity--on an illustrative set of MEG data. For five stimulation sessions, we found already for short epochs of duration of 250 and 500 ms that, although the majority of the studied epochs of single MEG trials were usually mean-stationary (KPSS test and PP test), they were classified as nonstationary due to their heteroscedasticity (White test). We also observed that the presence of external auditory stimulation did not significantly affect the findings regarding the stationarity of the data. We conclude that the combination of these tests allows a refined analysis of the stationarity of MEG and EEG time series. PMID- 22095175 TI - PDT in squamous cell carcinoma of the skin. AB - Topical photodynamic therapy (PDT) has been demonstrated to be an effective and safe treatment option for pre-malignancies such as actinic keratoses (AK) and Bowen's disease (BD), with an increasing amount of evidence indicating good long term outcomes. Studies comparing PDT to other options such as cryotherapy and 5 fluorouracil generally demonstrate that PDT is equal to or better than these therapies with respect to patient satisfaction, cosmesis, and efficacy for AK and BD. While there are studies using squamous cell carcinoma (SCC) cells to elucidate the cellular and molecular mechanisms of PDT, this therapy is currently not indicated for treating SCC and surgery is still the first line of therapy. There has been special interest in using PDT to prevent warts, basal cell carcinoma, AK, and BD in solid organ transplant recipients, as these skin lesions are more common in immunosuppressed patients, and trials have been somewhat successful and very promising. Pain remains an obstacle for some patients and techniques such as nerve blocks, cooling packs, and hydration have been attempted to mitigate pain with an overall reduction in pain scores. Optimizing PDT is still a priority and the delivery of pro-drug as well as induction of cellular differentiation are being explored as ways to improve the efficacy of PDT. Perhaps the most interesting use of PDT in treating SCC is the potential for a tumor-specific vaccine, which is currently being developed. PMID- 22095174 TI - Simultaneous care and melanoma: preliminary report about the psychoncological approach. AB - AIM: The main aim of the study was to investigate the efficacy of a "take-in- charge" model of advanced stage melanoma patients by a multidisciplinary team and highlight the psychological patterns of the disease. METHODS: The study sample involved 44 patients, 27 females and 17 males, who were given a "Questionnaire on Health Status SF-12" which provides two synthetic indexes, one related to physical health PCS-12, and the other to mental health MCS-12. The statistical data was collected through a preliminary analysis of principal components P.C. A., carried out with SPSS software. RESULTS: Comparing the scores obtained by the PCS and MCS indexes, the mean score is low: 6.52 out of 10 for PCS and 3.23 out of 10 for MCS. At first consultation, there is evidence which supports patients' need for psycho-oncological support. By dividing the sample patients into two subgroups, cutaneous melanoma and visceral melanoma, it should be noted that the first group obtained a mean of 4.75 for PCS and 3.77 for MCS and the second group 7.53 for PCS and 2.92 for MCS respectively. Therefore, the results show, at first consultation, a more complex situation for patients with cutaneous melanoma. CONCLUSION: The results of the study highlight the need to supply some form of psycho-oncological support to help patients while they adapt to the disease. Furthermore, different problems and different coping styles also emerged depending on whether the patient has cutaneous or visceral melanoma. The study therefore demonstrates the need to take into account such variables when devising a personal care system centered on the patient. PMID- 22095177 TI - Photodynamic therapy and plaque phase mycosis fungoides. AB - Photodynamic therapy (PDT) has been applied in the last years for the treatment of plaque mycosis fungoides (MF) with promising results. PDT is very useful in the management of patients with few plaques of MF unresponsive to other topical treatments or in patients with plaques in difficult to treat areas in which cosmetic outcome is important. PDT achieves similar results to other treatments and it is safe and well tolerated. Despite the simplicity of the technique optimal treatment parameters have not yet been defined. This article is a review of the literature of PDT and MF. PMID- 22095176 TI - Treatment of acne with photodynamic therapy. AB - Photodynamic therapy (PDT) with aminolevuninic acid (ALA) and methylaminolevulinate (MAL) can improve acne vulgaris. Topical application of these molecules results in significant build-up of porphyrins in sebaceous glands and the efficacy of PDT in acne is believed to be related in part to a decrease in sebaceous gland activity following light activation of the photosensitizer. Clinical development of photodynamic therapy with ALA or MAL for the treatment of acne has been limited by complexity of the PDT procedure, the pain caused during light exposure and by the intense phototoxic reaction observed in the days following treatment. These side effects can be significantly decreased by using a shorter incubation time, avoiding occlusion or using a lower light fluence but several studies have suggested that when milder PDT conditions are used the efficacy is not as good and is mostly driven by the effect of light alone. Using current knowledge many physicians are offering PDT as an alternative to their patients with acne. However more research is needed to determine the optimal treatment parameters and to design strategies to improve treatment tolerability. PMID- 22095178 TI - Is photodynamic therapy a solution for keloid? AB - Keloid is a common skin condition, especially in people of Asian and African decent. The treatment of keloid is still unsatisfactory. Photodynamic therapy (PDT) is a novel treatment for this condition, but is widely used in treating certain skin pre-malignant and malignant lesions due to its high efficiency and safety. Another aspect of PDT is its scarless (or minimal scarring) wound healing after treatment despite the fact that it causes skin inflammation. There are a few independent reports that indicate 5-aminolevulinic acid (ALA) or methylaminolevulinate (MAL)-PDT may be effective in keloid and hypertrophic scars. The mechanism is largely unknown. PDT may exert these effects by acting on keratinocytes and fibroblasts or directly on collagen/extracellular matrix (ECM) in keloid tissues, by inducing keloid fibroblast apoptosis/necrosis, modulating growth factor and cytokine expression, reducing collagen/ECM synthesis and causing degeneration of formed collagen/ECM. These potential mechanisms and the scope for topical PDT of keloids are considered in this article. PMID- 22095179 TI - Photodynamic therapy for photorejuvenation and non-oncologic indications: overview and update. AB - Topical photodynamic therapy (PDT) has shown to be effective in the treatment and prevention of non-melanoma skin cancer. PDT is also established as treatment modality for several non-oncologic indications. The aesthetic effects of PDT for photoaged skin are well documented. An improvement of lentigines, skin roughness, sallow complexion and fine wrinkles was demonstrated. A reduction of histological signs of photoaging as a decrease of elastotic material and expression of p53 together with induction of neocollagenesis was shown. The possible contemporaneous treatment of non-melanoma skin cancer renders PDT a novel and effective technique for skin rejuvenation. Controlled studies also demonstrated the efficacy of PDT in the treatment of acne vulgaris and HPV-induced skin diseases as verrucae vulgares and condylomata acuminata. In addition, there is evidence that certain sclerosing, inflammatory, granulomatous and infectious skin diseases may profit from PDT. In contrast to PDT of tumours, where cellular destruction is the main goal of the therapy, in PDT of inflammatory skin conditions it is probably the modulation of cellular functions that plays the main role. PMID- 22095180 TI - Recurrent skin eruption in patient with chronic lymphocytic leukemia and lymphocytic infiltrates of the dermis resembling Sweet's syndrome. AB - Sweet's syndrome (acute febrile dermatosis) is characterized by fever, peripheral neutrophil leukocytosis, acute onset of tender erythematous skin lesions (papules, nodules or plaques), and histological findings of a dense infiltrate consisting predominantly of mature neutrophils. Malignancy-associated Sweet's syndrome constitutes approximately 21% of patients, the majority of whom suffer from hematologic disorder. We report the case of patient with chronic lymphocytic leukemia with recurrent eruptions of tender, pseudovesiculated nodules and plaques with good response to corticosteroid therapy, resembling Sweet's syndrome. However, histological examination revealed lymphocytic infiltrate in the dermis, which made impossible to establish diagnosis of acute febrile dermatosis according to diagnostic criteria. Association of the skin eruptions with leukemia was implied by improvement of skin lesions after chemotherapy. We present review of the literature reporting cases with atypical histopathological presentations which preceded classical histological appearances, that were mainly associated with hematological malignancies and discuss them in the context of our patient. PMID- 22095181 TI - A case of bullous pemphigoid in infancy treated with local corticosteroids. AB - Bullous pemphigoid (BP) is an immune-mediated subepidermal vesiculobullous eruption, whose true incidence is unknown, but it is considered extremely rare in children, with a usually indolent course and rare relapses. Diagnosis is often belated, because of the invasive assessment with biopsy for typical immune pathologic findings to differentiate it from Dermatitis Herpetiformis and Linear IgA bullous dermatosis (LABD), more common in children. A 4-year-old girl presented with one year history of erythematous-edematous and erythematous bullous eruptions on the genitalia, periocular regions, dorsal and palmo-plantar surfaces. At onset erosions of the month and lips where considered a primary herpes simplex infection from the pediatrician, but repeated courses of systemic antivirals were completely ineffective, while application of a antibiotic steroidal cream was of partial benefit. Histopathology showed a dermo-epidermal blistering, with a marked eosinophilic infiltrate. Direct immunofluorescence showed a characteristic positive linear IgG and C3 band at the basement membrane zone (BMZ). Complete hematic-chemical and instrumental examinations gave normal results, excluding associated pathologies. Due to paucity of lesions and good response to local treatment with moderate potency cortisones, in agreement with the parents, no systemic therapy was started. No recurrence occurred in the 2 year follow-up after complete remission. The case is reported for the rarity of the childhood form, and the importance of the differential diagnosis for management and treatment. Good response to topical treatment is stressed, avoiding the risks of long-term systemic drug administration. PMID- 22095182 TI - Lyell syndrome due to ticlopidine. AB - The antiplatelets drug ticlopidine is widely used in patients suffering from cardiomyopathies, coronary cardiopathies and thromboembolic pathologies. The potential and frequently seen side effects are diarrhoea, hematological dyscrasias and rashes. We describe a case in which the use of ticlopidine in the treatment and prophylaxis of transit ischemic attacks triggered the unusual and rare complication of toxic epidermal necrolysis (TEN). We will then go on to analyse the clinical-pathological aspects and therapies through the use of i.v. immunoglobulins at high dosages that led to a full recovery of the patient. PMID- 22095183 TI - Multiple eccrine hidrocystomas: report of two cases. PMID- 22095184 TI - Etanercept induced hidradenitis suppurativa. PMID- 22095185 TI - Papular mycosis fungoides: a new case expanding the spectrum of phenotypic and clinical findings. PMID- 22095186 TI - New successful treatment of genital AIDS-related Kaposi's sarcoma resistant to systemic therapy with 595-nm pulsed dye laser. PMID- 22095187 TI - Hepatoblastoma in the Nordic countries. AB - Little is known about the etiology of hepatoblastoma. Because of the young age at diagnosis, several studies have looked at various birth characteristics. The purpose of our study was to investigate the incidence of hepatoblastoma in the Nordic countries and the association between selected birth characteristics and hepatoblastoma. Data from national cancer registries and birth registries in Denmark, Sweden, Norway and Finland 1985-2006 was used. Overall, 155 children with hepatoblastoma aged 0-14 years were included and individually matched to five controls drawn randomly from national population registries. The incidence rate of hepatoblastoma was 1.7 per million person-years with a predominance of boys (1.5:1). Incidence rate was highest before the age of 1 year (8.3 per million person-years). A higher risk of hepatoblastoma was found in children with birth weight <1,500 g [odds ratio (OR) = 9.5; 95% confidence interval (CI): 2.3 38.2], born preterm in week 22-32 (OR = 4.5; CI: 1.8-11.5) and Apgar scores <7 after 1 min (OR = 3.1; CI: 1.3-7.1) and 5 min (OR = 7.5; CI: 1.8-32.4). A doubling in risk was found in children who were large for gestational age (OR = 2.3; CI: 1.0-5.3). No associations were found with birth order, maternal age or maternal smoking. Our study indicates that intrauterine and/or neonatal factors are associated with increased risk of hepatoblastoma. These may include low birth weight and asphyxia leading to neonatal intensive care. Alternatively, the factors may be a consequence of hepatoblastoma developing in utero. PMID- 22095188 TI - Detection of neuroblastoma cells during clinical follow up: advanced flow cytometry and rt-PCR for tyrosine hydroxylase using both conventional and real time PCR. AB - PURPOSE: Real-time reverse-transcriptase PCR (RT-qPCR) or conventional RT-PCR (RT cPCR) detection of tyrosine hydroxylase (TH) is increasingly used to detect neuroblastoma (NB) cells in clinical samples. However, TH expression in normal tissues can limit its usefulness and make additional diagnostic strategies necessary. METHODS: We analysed TH in 857 tumour, bone marrow aspirate and peripheral blood stem cell samples from 65 NB patients using RT-cPCR, and compared results from 666 samples analysed by RT-qPCR. TH was investigated in 84 samples from patients with other diagnoses and 354 samples from healthy donors as controls, and 132 samples from the entire collection were evaluated for NB cells using 5-colour flow cytometry (FC). RESULTS: Cohen's kappa coefficient demonstrated a substantial agreement between RT-cPCR and RT-qPCR as well as RT cPCR and FC and a moderate agreement between RT-qPCR and FC. TH expression was also detected in samples from individual patients with Ewing sarcoma, nephroblastoma and rhabdomyosarcoma, but not from healthy donors. FC panels were an effective complementary strategy, detecting as few as 0.002% NB cells, characterised as CD45negCD9+CD81+CD56+ch14:18+GD2+ cells with occasional CD57+CD138+CD166+ expression. CONCLUSION: TH RT-qPCR alone is limited for detection of NB cells because of "false positives" in samples from patients with other diseases. Advanced FC may serve as a complementary method to detect residual NB, but needs further confirmation in larger patient cohorts. PMID- 22095189 TI - [Symptomatic foot shortening with subacute soft tissue swelling of the right tibia]. AB - A 13-year-old girl presented with load-dependent pain of the medial part of the right foot. The medical history revealed no trauma and no sports-related injury. X-ray examinations of the foot and lower leg showed subcortical increased sclerosis at the medial part of the tibia, the medial tarsal bones and of a bunion. Magnetic resonance imaging revealed corresponding findings with localized edema of the bone marrow within the increased subcortical sclerosis but no indications of subcutaneous fibrosis. The constellation is indicative of melorheostosis, a rare benign sclerosis of bones and soft tissue. Subcutaneous fibrosis and limb shortening are also common. PMID- 22095190 TI - Effects of the combination of low-level laser irradiation and recombinant human bone morphogenetic protein-2 in bone repair. AB - Low-level laser irradiation (LLLI) and recombinant human bone morphogenetic protein type 2 (rhBMP-2) have been used to stimulate bone formation. LLLI stimulates proliferation of osteoblast precursor cells and cell differentiation and rhBMP-2 recruits osteoprogenitor cells to the bone healing area. This in vivo study evaluated the effects of LLLI and rhBMP-2 on the bone healing process in rats. Critical bone defects were created in the parietal bone in 42 animals, and the animals were divided into six treatment groups: (1) laser, (2) 7 MUg of rhBMP 2, (3) laser and 7 MUg of rhBMP-2, (4) 7 MUg of rhBMP-2/monoolein gel, (5) laser and 7 MUg rhBMP-2/monoolein gel, and (6) critical bone defect controls. A gallium aluminum-arsenide diode laser was used (wavelength 780 nm, output power 60 mW, beam area 0.04 cm(2), irradiation time 80 s, energy density 120 J/cm(2), irradiance 1.5 W/cm(2)). After 15 days, the calvarial tissues were removed for histomorphometric analysis. Group 3 defects showed higher amounts of newly formed bone (37.89%) than the defects of all the other groups (P < 0.05). The amounts of new bone in defects of groups 1 and 4 were not significantly different from each other (24.00% and 24.75%, respectively), but were significantly different from the amounts in the other groups (P < 0.05). The amounts of new bone in the defects of groups 2 and 5 were not significantly different from each other (31.42% and 31.96%, respectively), but were significantly different from the amounts in the other groups (P < 0.05). Group 6 defects had 14.10% new bone formation, and this was significantly different from the amounts in the other groups (P < 0.05). It can be concluded that LLLI administered during surgery effectively accelerated healing of critical bone defects filled with pure rhBMP 2, achieving a better result than LLLI alone or the use of rhBMP-2 alone. PMID- 22095191 TI - Endometrial epithelial cell response to semen from HIV-infected men during different stages of infection is distinct and can drive HIV-1-long terminal repeat. AB - OBJECTIVES: Although more than 60% of HIV transmission occurs via semen, little is known about the immune impact of seminal plasma on HIV susceptibility. Here, we examined the level of selected immunomodulatory factors in seminal plasma from HIV-uninfected and therapy-naive, HIV-infected men in acute and chronic stages; the cytokine response elicited by seminal plasma in genital epithelial cells (GECs); and whether any GEC response to seminal plasma could drive HIV replication in infected T cells. METHODS: A panel of nine cytokines and chemokines was measured in seminal plasma from HIV-uninfected and HIV-infected men and in primary GEC cultures following seminal plasma exposure. HIV-long terminal repeat (LTR) activation was measured in 1G5 T cells exposed to supernatants from seminal plasma-treated GECs. RESULTS: Pro-inflammatory cytokines and chemokines were present at significantly higher levels in seminal plasma from acute men, whereas transforming growth factor (TGF)-beta1 was significantly higher in seminal plasma from chronic men. Pro-inflammatory cytokine production by GECs was significantly decreased following incubation with seminal plasma from chronic men. Blocking the TGF-beta1 receptor in GECs prior to seminal plasma exposure enhanced pro-inflammatory cytokine production. Exposure to seminal plasma activated nuclear factor (NF)-kappaB in GECs and blocking it significantly reduced pro-inflammatory cytokine production. GEC responses to seminal plasma, especially from acute men, significantly activated HIV-LTR activation in 1G5 T cells. CONCLUSION: Immunomodulatory factors in seminal plasma vary, depending on presence and stage of HIV infection. Exposure to seminal plasma leads to NF-kappaB activation and pro-inflammatory cytokine production, whereas TGF-beta in seminal plasma may suppress pro-inflammatory cytokine production by GECs. GEC responses to seminal plasma can activate HIV-LTR in infected CD4(+) T cells. PMID- 22095193 TI - Bacterial vaginosis, HIV serostatus and T-cell subset distribution in a cohort of East African commercial sex workers: retrospective analysis. AB - OBJECTIVE: Although bacterial vaginosis is a known correlate of HIV infection, no previous studies have investigated whether women defined as HIV-exposed seronegative (HESN) are less likely to have bacterial vaginosis. Little is known about the effects of bacterial vaginosis on systemic immune activation associated with HIV+ serostatus. DESIGN: Cohort-based retrospective analysis of bacterial vaginosis in relation to HESN status, HIV+ serostatus and peripheral T-helper cells, with cross-sectional analysis of bacterial vaginosis in relation to peripheral T-regulatory cells (Tregs). METHODS: Bacterial vaginosis diagnosis by Gram stain and determination of systemic CD4(+) and CD8(+) T-helper cell frequency by flow cytometry for 3504 vaginal samples from 988 commercial sex workers over 4 years. Treg phenotyping by FoxP3 staining and multiparameter flow cytometry in peripheral blood of 97 women at a single time-point. RESULTS: No differences in bacterial vaginosis diagnosis were observed between HESN and other HIV-negative (HIV-N) controls; however, HIV+ women were more likely to be diagnosed with bacterial vaginosis compared to all HIV-negative women (HESN/HIV-N combined). HIV+ women with bacterial vaginosis had significantly higher CD4(+)/CD8(+) T-helper cell counts and a lower CD4/CD8 ratio, as well as fewer Tregs as a proportion of total T-helper cells, compared to bacterial vaginosis negative women. The number of bacterial vaginosis diagnoses in this cohort has decreased significantly over time. CONCLUSION: Bacterial vaginosis is associated with HIV serostatus and shifts in distribution of T-cell subsets. A concomitant reduction in bacterial vaginosis and HIV infections over time suggests that the elucidation of bacterial vaginosis-HIV interactions will be critical to further understanding of HIV pathogenesis and prevention in this high-risk group. PMID- 22095194 TI - Mortality and loss to follow-up in the first year of ART: Malawi national ART programme. AB - OBJECTIVES: To analyse mortality, loss to follow-up (LTFU) and retention on antiretroviral treatment (ART) in the first year of ART across all age groups in the Malawi national ART programme. DESIGN: Cohort study including all patients who started ART in Malawi's public sector clinics between 2004 and 2007. METHODS: ART registers were photographed, information entered into a database and merged with data from clinics with electronic records. Rates per 100 patient-years and cumulative incidence of retention were calculated. Subhazard ratios (sHRs) of outcomes adjusted for patient and clinic-level characteristics were calculated in multivariable analysis, applying competing risk models. RESULTS: A total of 117,945 patients contributed 85,246 person-years: 1.0% were infants below 2 years, 7.4% children 2-14, 7.5% young people 15-24, and 84.2% adults 25 years and above. Sixty percent of patients were female: women outnumbered men from age 14 to 35 years. Mortality and LTFU were higher in men from age 20 years. Infants and young people had the highest rates per 100 person-years for mortality (23.0 and 19.4) and LTFU (24.7 and 19.3), and the highest adjusted relative risks compared to age group 25-34 years: sHRs were 1.37 [95% confidence interval (CI) 1.17-1.60] and 1.17 (95% CI 1.10-1.25) for death and 1.37 (95% CI 1.18-1.59) and 1.27 (95% CI 1.19-1.35) for LTFU, respectively. CONCLUSION: In this country-wide study patients aged 0-1 and 15-24 years had the highest risk of death and LTFU, and from age 20 men were at higher risk than women. Interventions to improve outcomes in these patient groups are required. PMID- 22095195 TI - Incidence of low and high-energy fractures in persons with and without HIV infection: a Danish population-based cohort study. AB - OBJECTIVE: To compare fracture risk in persons with and without HIV infection and to examine the influence of highly active antiretroviral therapy (HAART) initiation on risk of fracture. DESIGN: Population-based nationwide cohort study using Danish registries. METHODS: Outcome measures were time to first fracture at any site, time to first low-energy and high-energy fracture in HIV-infected patients (n = 5306) compared with a general population control cohort (n = 26 530) matched by sex and age during the study period 1995-2009. Cox regression analyses were used to estimate incidence rate ratios (IRRs). RESULTS: HIV infected patients had increased risk of fracture [IRR 1.5, 95% confidence interval (CI) 1.4-1.7] compared with population controls. The relative risk was lower in HIV-monoinfected patients (IRR 1.3, 95% CI 1.2-1.4) than in HIV/hepatitis C virus (HCV)-coinfected patients (IRR 2.9, 95% CI 2.5-3.4).Both HIV-monoinfected and HIV/HCV-coinfected patients had increased risk of low-energy fracture, IRR of 1.6 (95% CI 1.4-1.8) and 3.8 (95% CI 3.0-4.9). However, only HIV/HCV-coinfected patients had increased risk of high-energy fracture, IRR of 2.4 (95% CI 2.0-2.9). Among HIV-monoinfected patients the risk of low-energy fracture was only significantly increased after HAART exposure, IRR of 1.8 (95% CI 1.5-2.1). The increased risk in HAART-exposed patients was not associated with CD4 cell count, prior AIDS, tenofovir or efavirenz exposure, but with comorbidity and smoking. CONCLUSION: HIV-infected patients had increased risk of fracture compared with population controls. Among HIV-monoinfected patients the increased risk was observed for low-energy but not for high-energy fractures, and the increased risk of low-energy fracture was only observed in HAART-exposed patients. PMID- 22095197 TI - Periodic presumptive treatment of curable sexually transmitted infections among sex workers: a systematic review. AB - BACKGROUND: Unprotected sex work remains a major driver of HIV/sexually transmitted infection (STI) epidemics in many countries. STI treatment can lower disease burden, complications and prevalence of HIV cofactors. Periodic presumptive treatment (PPT) has been used with sex workers to reduce their high burden of largely asymptomatic STIs. The objective of this review is to assess benefits and harms of PPT among female sex workers. METHODS: We searched MEDLINE for studies related to sex work and STIs during 1990-2010, extracted data from eligible studies in duplicate and conducted meta-analysis by study design using random effects models. RESULTS: Two thousand, three hundred and fifteen articles were screened, 18 studies met inclusion criteria and 14 were included in meta analyses. One published randomized controlled trial (RCT) reported significant reductions of gonorrhoea (Neisseria gonorrhoeae) [rate ratio (RR) 0.46, 95% confidence interval (CI) 0.31-0.68] and chlamydia (Chlamydia trachomatis) (RR 0.38, 95%CI 0.26-0.57), but no effect on serologic syphilis (RR 1.02, 95%CI 0.54 1.95). Similar results were seen for N. gonorrhoeae and C. trachomatis in pooled analyses, including data from one unpublished RCT and across study designs, and correlated with initial prevalence (R(2) = 0.155). One observational study reported genital ulcer disease (GUD) declines in sex workers, and two reported impact among male client populations for N. gonorrhoeae [odds ratio (OR) 0.60, 95% CI 0.38-0.94], C. trachomatis (OR 0.47, 95% CI 0.31-0.71) and GUD (OR 0.21, 95% CI 0.11-0.42). No studies reported evidence of risk compensation or antibiotic resistance. CONCLUSION: PPT can reduce prevalence of gonorrhoea, chlamydia and ulcerative STIs among sex workers in whom prevalence is high. Sustained STI reductions can be achieved when PPT is implemented together with peer interventions and condom promotion. Additional benefits may include impact on STI and HIV transmission at population level. PMID- 22095196 TI - Myeloid dendritic cells isolated from tissues of SIV-infected Rhesus macaques promote the induction of regulatory T cells. AB - OBJECTIVE: To determine whether the ability of primary myeloid dendritic cells (mDCs) to induce regulatory T cells (Treg) is affected by chronic simian immunodeficiency virus (SIV) infection. DESIGN: Modulation of dendritic cell activity with the aim of influencing Treg frequency may lead to new treatment options for HIV and strategies for vaccine development. METHODS: Eleven chronically infected SIV(+) Rhesus macaques were compared with four uninfected animals. Immature and mature mDCs were isolated from mesenteric lymph nodes and spleen by cell sorting and cultured with purified autologous non-Treg (CD4(+)CD25(-) T cells). CD25 and FOXP3 up-regulation was used to assess Treg induction. RESULTS: The frequency of splenic mDC and plasmacytoid dendritic cell was lower in infected animals than in uninfected animals; their frequency in the mesenteric lymph nodes was not significantly altered, but the percentage of mature mDCs was increased in the mesenteric lymph nodes of infected animals. Mature splenic or mesenteric mDCs from infected animals were significantly more efficient at inducing Treg than mDCs from uninfected animals. Mature mDCs from infected macaques induced more conversion than immature mDCs. Splenic mDCs were as efficient as mesenteric mDCs in this context and CD103 expression by mDCs did not appear to influence the level of conversion. CONCLUSIONS: Tissue mDCs from SIV-infected animals exhibit an enhanced capability to induce Treg and may contribute to the accumulation of Treg in lymphoid tissues during progressive infection. The activation status of dendritic cell impacts this process but the capacity to induce Treg was not restricted to mucosal dendritic cells in infected animals. PMID- 22095198 TI - Prime-boost regimens with adjuvanted synthetic long peptides elicit T cells and antibodies to conserved regions of HIV-1 in macaques. AB - OBJECTIVES: Administration of synthetic long peptides (SLPs) derived from human papillomavirus to cervical cancer patients resulted in clinical benefit correlated with expansions of tumour-specific T cells. Because vaginal mucosa is an important port of entry for HIV-1, we have explored SLP for HIV-1 vaccination. Using immunogen HIVconsv derived from the conserved regions of HIV-1, we previously showed in rhesus macaques that SLP.HIVconsv delivered as a boost increased the breath of T-cell specificities elicited by single-gene vaccines. Here, we compared and characterized the use of electroporated pSG2.HIVconsv DNA (D) and imiquimod/montanide-adjuvanted SLP.HIVconsv (S) as priming vaccines for boosting with attenuated chimpanzee adenovirus ChAdV63.HIVconsv (C) and modified vaccinia virus Ankara MVA.HIVconsv (M). DESIGN: Prime-boost regimens of DDDCMS, DSSCMS and SSSCMS in rhesus macaques. METHODS: Animals' blood was analysed regularly throughout the vaccination for HIV-1-specific T-cell and antibody responses. RESULTS: We found that electroporation spares DNA dose, both SLP.HIVconsv and pSG2.HIVconsv DNA primed weakly HIVconsv-specific T cells, regimen DDDCM induced the highest frequencies of oligofunctional, proliferating CD4(+) and CD8(+) T cells, and a subsequent SLP.HIVconsv boost expanded primarily CD4(+) cells. DSS was the most efficient regimen inducing antibodies binding to regions of trimeric HIV-1 Env, which are highly conserved among the four major global clades, although no unequivocal neutralizing activity was detected. CONCLUSION: The present results encourage evaluation of the SLP.HIVconsv vaccine modality in human volunteers along the currently trialled pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines. These results are discussed in the context of the RV144 trial outcome. PMID- 22095199 TI - Fine and ultrafine particles emitted from laser printers as indoor air contaminants in German offices. AB - PURPOSE: Various publications indicate that the operation of laser printers and photocopiers may be associated with health effects due to the release of gaseous components and fine and ultrafine particles (UFP). However, only sparse studies are available that evaluate the possible exposure of office workers to printer emissions under real conditions. Therefore, the aim of our study was to assess the exposure of office workers to particulate matter released from laser printers and photocopiers. METHODS: Concentrations of fine particles and UFP were measured before, during, and after the operation of laser printing devices in 63 office rooms throughout Germany. Additionally, the particles were characterized by electron microscopy and energy-dispersive X-ray spectroscopy. RESULTS: A significant increase of fine particles and UFP was identified in ambient workplace air during and after the printing processes. Particle fractions between 0.23 and 20 MUm emitted by the office machines significantly affect particle mass concentrations while printing 500 pages, i.e., during the printing process, PM(0.23-20), PM(2.5), and PM(10) concentrations increased in 43 out of the evaluated 62 office rooms investigated. Additionally, a significant increase was observed in submicrometer particles, with median particle number concentrations of 6,503 particles/cm(3) before and 18,060 particles/cm(3) during the printing process. CONCLUSIONS: Our data indicate that laser printers and photocopiers could be a relevant source of fine particles and particularly UFP in office rooms. PMID- 22095200 TI - A tiered ecological risk assessment of three chlorophenols in Chinese surface waters. AB - INTRODUCTION: The ecological risks posed by three chlorophenols (CPs), 2,4 dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) in Chinese surface waters were assessed. MATERIALS AND METHODS: This was achieved by applying a tiered ecological risk assessment (ERA) approach ranging from deterministic methods to probabilistic options to measured concentrations of CPs in surface water of seven major watersheds and three drainage regions in China and the chronic toxicity data for indigenous Chinese species. RESULTS AND DISCUSSION: The results show that the risks of three chlorophenols are ranked PCP>2,4-DCP~2,4,6-TCP. PCP posed little ecological risk while 2,4-DCP and 2,4,6-TCP posed negligible or de minimis risk in Chinese surface water. However, the risks varied with different river basins, for example, PCP posed some ecological risk in the Yangtze, Huaihe, and Pearl Rivers. The magnitude of 2,4-DCP and 2,4,6-TCP pollution in North China was more serious than that in South China. CONCLUSION: The probabilistic risk assessment approach, which can provide more information for risk managers and decision makers, was favored over the screening-level single-value estimate method. However, the results from all tiers of the ERA methods in the framework were consistent with each other. PMID- 22095201 TI - Dipyridylketone as a versatile ligand precursor for new cationic heteroleptic cyclometalated iridium complexes. AB - Three new bis-cyclometalated iridium(III) complexes, of general formula [Ir(2 phenylpyridine)(2)(L)](+), are reported. The compounds contain a dipyridine-type ligand (L) derived from di-2-pyridylketone (dipyridin-2-ylmethanol, 2,2' (hydrazonomethylene)dipyridine and 3-hydroxy-3,3-di(pyridine-2-yl)propanenitrile) and were synthesized through two different reaction pathways. The alternative synthetic pathway herein proposed, namely the direct reactions on the complex [Ir(2-phenylpyridine)(2)(2,2'-dipyridylketone)](+), overcame the inconveniences encountered with the standard reaction between the dimeric precursor [Ir(2 phenylpyridine)(2)(MU-Cl)](2) and the ancillary ligands (L). The photophysical characterization of the iridium complexes reveals that modifications on the ancillary ligand introduce large changes in the photophysical behaviour of the complexes. High emission quantum yield is associated with the presence of a saturated carbon between the two pyridyl moieties: [Ir(2-phenylpyridine)(2)(2,2' dipyridylketone)](+) and [Ir(2-phenylpyridine)(2)(2,2' (hydrazonomethylene)dipyridine)](+) are extremely low emissive, while [Ir(2 phenylpyridine)(2)(dipyridin-2-ylmethanol)](+) and [Ir(2-phenylpyridine)(2)(3 hydroxy-3,3-di(pyridine-2-yl)propanenitrile)](+) are good photoemitters. DFT and TD-DFT calculations confirmed the mixed LC/MLCT character of the excited states involved in the absorption and emission processes and highlighted the role of the pi-conjugation between the two subunits of the ancillary ligand in determining the nature of the LUMO. PMID- 22095202 TI - Disorders of sexual development in the domestic horse, Equus caballus. AB - Abnormalities of sexual development causing infertility in horses have been investigated since the early 1970's. Conventional cytogenetic analysis by karyotyping has been the primary tool used to investigate these horses. Abnormalities have a broad range, from a phenotypically normal mare with gonadal dysgenesis to a horse with ambiguous external genitalia and internal male and female organs. Cytogenetic analysis can determine genetic sex but cannot identify mutations or deletions of genes involved in the sex determination pathway. Molecular technologies have been developed to confirm cytogenetic results and to aid in identifying the genetic causes of abnormal sex determination in horses. In this paper, we review the historical development of methods used to understand abnormal sexual development in the horse as well as summarize cases reported over the last 40-50 years. PMID- 22095203 TI - Evaluation of urban sprawl and urban landscape pattern in a rapidly developing region. AB - Urban sprawl is a worldwide phenomenon happening particularly in rapidly developing regions. A study on the spatiotemporal characteristics of urban sprawl and urban pattern is useful for the sustainable management of land management and urban land planning. The present research explores the spatiotemporal dynamics of urban sprawl in the context of a rapid urbanization process in a booming economic region of southern China from 1979 to 2005. Three urban sprawl types are distinguished by analyzing overlaid urban area maps of two adjacent study years which originated from the interpretation of remote sensed images and vector land use maps. Landscape metrics are used to analyze the spatiotemporal pattern of urban sprawl for each study period. Study results show that urban areas have expanded dramatically, and the spatiotemporal landscape pattern configured by the three sprawl types changed obviously. The different sprawl type patterns in five study periods have transformed significantly, with their proportions altered both in terms of quantity and of location. The present research proves that urban sprawl quantification and pattern analysis can provide a clear perspective of the urbanization process during a long time period. Particularly, the present study on urban sprawl and sprawl patterns can be used by land use and urban planners. PMID- 22095204 TI - Physician-patient communication regarding colorectal cancer screening is lacking. PMID- 22095206 TI - [Effects of the great East Japan earthquake on industries and laborers in Fukushima prefecture]. PMID- 22095205 TI - [Comparison of lifestyle, mental stress, and medical check-up results between Tanshin-funin workers and workers living with their families]. AB - OBJECTIVES: We conducted a comparative analysis of lifestyle, mental stress, and medical check-up results between tanshin-funin workers and workers living with their families. METHODS: Study participants were 3,026 married men, aged 40-59 yr, who worked at a large financial firm in Japan. Tanshin-funin was defined as married men separated from their families due to workplace assignments, as determined by a self-administered questionnaire in 2004. Participants' lifestyle factors, including exercise, alcohol and smoking consumption, and dietary habits, and mental stress, including lack of vigor, irritability, fatigue, anxiety, depressed mood, and physical complaints, were examined using a self-administered questionnaire. Medical check-ups conducted in 2004 included measurements of BMI, SBP, DBP, FBS, GOT, GPT, gamma-GTP, TC, TG, HDL, RBC, and WBC. RESULTS: An analysis of lifestyle factors, using the chi(2) test, indicated that fewer tanshin-funin workers exercise, and that they had fewer regularly-scheduled meals. Tanshin-funin workers smoked more and consumed more alcohol, but ate fewer green and yellow vegetables. Tanshin-funin workers had fewer commuting hours and took fewer days off. Tanshin-funin workers also suffered more frequently from irritability and anxiety. A regression analysis, adjusted for age and smoking status, indicated that levels of TC, TG, and WBC for tanshin-funin workers were higher than workers living with their families. CONCLUSIONS: The lifestyle habits of tanshin-funin workers, such as dietary habits, were worse than those of workers living with their families, and tanshin-funin workers suffered from more irritability and anxiety. Clinical markers, such as dyslipidemia, were worse among tanshin-funin workers than among workers living with their families. PMID- 22095207 TI - Early neuromuscular electrical stimulation to improve quadriceps muscle strength after total knee arthroplasty: a randomized controlled trial. AB - BACKGROUND: The recovery of quadriceps muscle force and function after total knee arthroplasty (TKA) is suboptimal, which predisposes patients to disability with increasing age. OBJECTIVE: The purpose of this investigation was to evaluate the efficacy of quadriceps muscle neuromuscular electrical stimulation (NMES), initiated 48 hours after TKA, as an adjunct to standard rehabilitation. DESIGN: This was a prospective, longitudinal randomized controlled trial. METHODS: Sixty six patients, aged 50 to 85 years and planning a primary unilateral TKA, were randomly assigned to receive either standard rehabilitation (control) or standard rehabilitation plus NMES applied to the quadriceps muscle (initiated 48 hours after surgery). The NMES was applied twice per day at the maximum tolerable intensity for 15 contractions. Data for muscle strength, functional performance, and self-report measures were obtained before surgery and 3.5, 6.5, 13, 26, and 52 weeks after TKA. RESULTS: At 3.5 weeks after TKA, significant improvements with NMES were found for quadriceps and hamstring muscle strength, functional performance, and knee extension active range of motion. At 52 weeks, the differences between groups were attenuated, but improvements with NMES were still significant for quadriceps and hamstring muscle strength, functional performance, and some self-report measures. LIMITATIONS: Treatment volume was not matched for both study arms; NMES was added to the standard of care treatment. Furthermore, testers were not blinded during testing, but used standardized scripts to avoid bias. Finally, some patients reached the maximum stimulator output during at least one treatment session and may have tolerated more stimulation. CONCLUSIONS: The early addition of NMES effectively attenuated loss of quadriceps muscle strength and improved functional performance following TKA. The effects were most pronounced and clinically meaningful within the first month after surgery, but persisted through 1 year after surgery. PMID- 22095208 TI - Physical fitness in patients with ankylosing spondylitis: comparison with population controls. AB - BACKGROUND: Although flexibility traditionally has been the main focus for physical therapy in patients with ankylosing spondylitis (AS), there is now evidence for an increased risk of cardiovascular diseases (CVDs) in this group. OBJECTIVE: The purposes of this study were: (1) to compare physical fitness (cardiorespiratory fitness, muscular capacity, flexibility, and balance) in patients with AS and controls and (2) to explore associations between physical fitness and disease activity in the patient group. DESIGN: This was a cross sectional study. METHODS: The physical fitness variables were cardiorespiratory fitness (treadmill test for estimation of peak oxygen uptake [V(O(2))peak]), muscular capacity (push-ups test), balance (30-second single-leg stand and walking in a figure-of-eight pattern), and flexibility (Bath Ankylosing Spondylitis Metrology Index [BASMI]). The Ankylosing Spondylitis Disease Activity Score (ASDAS) was used to assess disease activity. Group differences and associations were tested with the chi-square test for categorical variables, the Mann-Whitney U test for ordinal variables, and analysis of covariance for continuous variables. RESULTS: One hundred forty-nine of 250 of the invited patients with AS and 133 of 329 of the invited controls were included in the study. The mean ASDAS score of the patient group was 2.3 (range=0.5-4.7), and the median disease duration was 23 years (range=7-55). The patient group had significantly lower V(O(2)) peak values, with a mean difference of -2.7 mL.kg( 1).min(-1) (95% confidence interval=-4.3, -1.1), and higher BASMI scores, with a mean difference of 1.6 (95% confidence interval=1.5, 1.8), compared with the control group. No group differences were found in balance or muscular capacity. In the patient group, significant inverse associations were found between ASDAS scores and V(O(2))peak and muscular capacity. LIMITATIONS: The response rate was lower in the control group (40.4%) than in the patient group (59.6%). CONCLUSION: The lower cardiorespiratory fitness and reduced flexibility in the AS group indicate that physical therapy programs should include cardiorespiratory fitness exercises as a basic component to reduce the risk of cardiovascular disease. PMID- 22095209 TI - Complex versus simple ankle movement training in stroke using telerehabilitation: a randomized controlled trial. AB - BACKGROUND: Telerehabilitation allows rehabilitative training to continue remotely after discharge from acute care and can include complex tasks known to create rich conditions for neural change. OBJECTIVES: The purposes of this study were: (1) to explore the feasibility of using telerehabilitation to improve ankle dorsiflexion during the swing phase of gait in people with stroke and (2) to compare complex versus simple movements of the ankle in promoting behavioral change and brain reorganization. DESIGN: This study was a pilot randomized controlled trial. SETTING: Training was done in the participant's home. Testing was done in separate research labs involving functional magnetic resonance imaging (fMRI) and multi-camera gait analysis. PATIENTS: Sixteen participants with chronic stroke and impaired ankle dorsiflexion were assigned randomly to receive 4 weeks of telerehabilitation of the paretic ankle. INTERVENTION: Participants received either computerized complex movement training (track group) or simple movement training (move group). MEASUREMENTS: Behavioral changes were measured with the 10-m walk test and gait analysis using a motion capture system. Brain reorganization was measured with ankle tracking during fMRI. RESULTS: Dorsiflexion during gait was significantly larger in the track group compared with the move group. For fMRI, although the volume, percent volume, and intensity of cortical activation failed to show significant changes, the frequency count of the number of participants showing an increase versus a decrease in these values from pretest to posttest measurements was significantly different between the 2 groups, with the track group decreasing and the move group increasing. LIMITATIONS: Limitations of this study were that no follow-up test was conducted and that a small sample size was used. CONCLUSIONS: The results suggest that telerehabilitation, emphasizing complex task training with the paretic limb, is feasible and can be effective in promoting further dorsiflexion in people with chronic stroke. PMID- 22095210 TI - White matter hyperintensity as a factor associated with delayed mood disorders in patients with acute ischemic stroke. AB - BACKGROUND: Mood disorder is a frequent complication of stroke. Comorbid depressive and anxiety disorders are very common, indicating that it is advisable to assess both disorders at the same time. The aim of the present study was to examine the prevalence of post-stroke depression (PSD) and poststroke anxiety (PSA) at baseline and to evaluate factors related to delayed PSD and PSA at 3 months after stroke onset. METHODS: This was a prospectively registered and retrospectively analyzed study of patients with acute ischemic stroke between January 2009 and March 2010. Patients included in this study were interviewed in order to evaluate their Hospital Anxiety and Depression Scale (HADS) scores. In this study, each depression and anxiety score was dichotomized into 'nondepressive and nonanxious' (HADS-D and HADS-A <=7) and 'depressive and anxious' (HADS-D and HADS-A >7). Multiple logistic regression analysis was used to evaluate the independent factors of depressive and anxious symptoms 3 months after stroke onset. RESULTS: Of the 133 patients, 47.4% were 'depressive' and 56.4% were 'anxious' at baseline. The depressive and anxious groups had a significantly higher frequency of severe white matter hyperintensity (WMH) than the nondepressive and nonanxious groups (p < 0.05). The independent factors of PSD and PSA at 3 months were deep white matter hyperintensities (DWMH) and modified Rankin scale 0 to 1 at 3 months. CONCLUSION: In conclusions, the results of our study demonstrated that delayed depression and anxiety after ischemic stroke were related to the severity of DWMH and unfavorable outcomes at 3 months, regardless of anti-anxiety treatment. Our results suggested that WMH might be associated with pathomechanism of delayed depression and anxiety. PMID- 22095211 TI - Exfoliation of copper hydroxysalt in water and the conversion of the exfoliated layers to cupric and cuprous oxide nanoparticles. AB - P-aminobenzoate-intercalated copper hydroxysalt was prepared by coprecipitation at high pH (~12). As the pH was reduced to ~7 on washing with water, the development of partial positive charge on the amine end of the intercalated anion caused repulsion between the layers leading to delamination and colloidal dispersion of monolayers of copper hydroxysalt in water. The dispersed copper hydroxysalt monolayers were used as precursors for the synthesis of copper(I)/(II) oxide nanoparticles at room temperature. While the hydroxysalt layers yielded spindle-shaped CuO particles when left to stand, they formed hollow spherical nanoparticles of Cu(2)O when treated with an alkaline solution of ascorbic acid. PMID- 22095213 TI - Impaired visual search in rats reveals cholinergic contributions to feature binding in visuospatial attention. AB - The visual search task established the feature integration theory of attention in humans and measures visuospatial attentional contributions to feature binding. We recently demonstrated that the neuromodulator acetylcholine (ACh), from the nucleus basalis magnocellularis (NBM), supports the attentional processes required for feature binding using a rat digging-based task. Additional research has demonstrated cholinergic contributions from the NBM to visuospatial attention in rats. Here, we combined these lines of evidence and employed visual search in rats to examine whether cortical cholinergic input supports visuospatial attention specifically for feature binding. We trained 18 male Long-Evans rats to perform visual search using touch screen-equipped operant chambers. Sessions comprised Feature Search (no feature binding required) and Conjunctive Search (feature binding required) trials using multiple stimulus set sizes. Following acquisition of visual search, 8 rats received bilateral NBM lesions using 192 IgG saporin to selectively reduce cholinergic afferentation of the neocortex, which we hypothesized would selectively disrupt the visuospatial attentional processes needed for efficient conjunctive visual search. As expected, relative to sham lesioned rats, ACh-NBM-lesioned rats took significantly longer to locate the target stimulus on Conjunctive Search, but not Feature Search trials, thus demonstrating that cholinergic contributions to visuospatial attention are important for feature binding in rats. PMID- 22095212 TI - Subventricular zone-derived neuroblasts use vasculature as a scaffold to migrate radially to the cortex in neonatal mice. AB - Neurons continue to be generated in the subventricular zone (SVZ) throughout postnatal development and adulthood in rodents. Whereas in adults, virtually all neuroblasts migrate tangentially to the olfactory bulb via the rostral migratory stream (RMS), in neonates, a substantial fraction migrate radially through the corpus callosum (CC) to the cortex. Mechanisms of radial cortical migration have remained unknown. We investigated this by taking recourse to enhanced green fluorescent protein (EGFP)-labeled neuroblasts in the CC and deep cortical layers of neonatal mice and found that they are frequently located adjacent to vasculature. Using time-lapse 2-photon microscopy in acute brain slices, we demonstrate that EGFP-labeled neuroblasts migrate along blood vessels. Although in close proximity to blood vessels, migrating neuroblasts are separated from endothelial cells by 1-2 layers of astrocytic processes, as revealed by electron microscopal studies of retrovirally labeled postnatally born cells. We propose that 2 factors could contribute to the decline of radial migration to the cortex during postnatal development, namely the establishment of a glial sheath delineating the RMS and a gradual decrease in the density of blood vessels in the CC. Together, our data provide evidence for a new mode of radial cortical migration of SVZ-generated neurons involving vasculature and astrocytes. PMID- 22095214 TI - Wnt signaling has opposing roles in the developing and the adult brain that are modulated by Hipk1. AB - The canonical Wnt/Wingless pathway is implicated in regulating cell proliferation and cell differentiation of neural stem/progenitor cells. Depending on the context, beta-Catenin, a key mediator of the Wnt signaling pathway, may regulate either cell proliferation or differentiation. Here, we show that beta-Catenin signaling regulates the differentiation of neural stem/progenitor cells in the presence of the beta-Catenin interactor Homeodomain interacting protein kinase-1 gene (Hipk1). On one hand, Hipk1 is expressed at low levels during the entire embryonic forebrain development, allowing beta-Catenin to foster proliferation and to inhibit differentiation of neural stem/progenitor cells. On the other hand, Hipk1 expression dramatically increases in neural stem/progenitor cells, residing within the subventricular zone (SVZ), at the time when the canonical Wnt signaling induces cell differentiation. Analysis of mouse brains electroporated with Hipk1, and the active form of beta-Catenin reveals that coexpression of both genes induces proliferating neural stem/progenitor cells to escape the cell cycle. Moreover, in SVZ derive neurospheres cultures, the overexpression of both genes increases the expression of the cell-cycle inhibitor P16Ink4. Therefore, our data confirm that the beta-Catenin signaling plays a dual role in controlling cell proliferation/differentiation in the brain and indicate that Hipk1 is the crucial interactor able to revert the outcome of beta-Catenin signaling in neural stem/progenitor cells of adult germinal niches. PMID- 22095215 TI - Occipital cortical thickness predicts performance on pitch and musical tasks in blind individuals. AB - The behavioral and neurofunctional consequences of blindness often include performance enhancements and recruitment of occipital regions for nonvisual tasks. How the neuroanatomical changes resulting from this sensory loss relate to these functional changes is, however, less clear. Previous studies using cortical thickness (CT) measures have shown thicker occipital cortex in early-blind (EB) individuals compared with sighted controls. We hypothesized that this finding reflects the crossmodal plasticity often observed in blind individuals and thus could reflect behavioral adaptations. To address this issue, CT measures in blind (early and late) and sighted subjects were obtained along with several auditory behavioral measures in an attempt to relate behavioral and neuroanatomical changes. Group contrasts confirmed previous results in showing thicker occipital cortex in the EB. Regression analyses between CT measures across the whole brain of all blind individuals with the behavioral scores from 2 tasks in which EB subjects were superior (pitch and melody discrimination) showed that CT of occipital areas was directly related to behavioral enhancements. These findings constitute a compelling demonstration that anatomical changes in occipital areas are directly related to heightened behavioral abilities in the blind and hence support the idea that these anatomical features reflect adaptive compensatory plasticity. PMID- 22095217 TI - A polymorphism at the miR-502 binding site in the 3'-untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome. AB - MicroRNAs (miRNAs) can bind to the 3'-untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis and tumorigenesis. Genetic polymorphisms in the 3' UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. The histone methyltransferase SET8 has been reported to methylate TP53 and regulate genomic stability. We analyzed a single-nucleotide polymorphism (rs16917496) within the miR-502 miRNA seed region for the 3'-UTR of SET8 in Chinese patients with hepatocellular carcinoma (HCC). The SET8 CC genotype was independently associated with longer postoperative survival in patients with HCC by multivariate analysis (relative risk, 0.175; 95% CI = 0.053-0.577; p = 0.004). The SET8 CC genotype was associated with reduced SET8 protein levels based on the immunostaining of 51 HCC tissue samples. We also found that the low SET8 levels were associated with longer HCC survival. Our data suggest that SET8 modifies HCC outcome by altering its expression, which depends, at least in part, on its binding affinity with miR-502. The analysis of genetic polymorphisms in miRNA binding sites can help to identify patient subgroups that are at high risk for poor disease outcomes. PMID- 22095216 TI - Dissociation between verbal response initiation and suppression after prefrontal lesions. AB - Some of the most striking symptoms after prefrontal damage are reduction of behavioral initiation and inability to suppress automatic behaviors. However, the relation between these 2 symptoms and the location of the lesions that cause them are not well understood. This study investigates the cerebral correlates of initiation and suppression abilities assessed by the Hayling Sentence Completion Test, using the human lesion approach. Forty-five patients with focal brain lesions and 110 healthy matched controls were examined. We combined a classical group approach with 2 voxel-based lesion methods. The results show several critical prefrontal regions to Hayling Test performance, associated with either common or differential impairment in "initiation" and "suppression" conditions. A crucial role for medial rostral prefrontal cortex (BA 10) in the initiation condition was shown by both group and lesion-mapping methods. A posterior inferolateral lesion provoked both initiation and suppression slowness, although to different degrees. An orbitoventral region was associated with errors in the suppression condition. These findings are important for clinical practice since they indicate that the brain regions required to perform a widely used and sensitive neuropsychological test but also shed light on the regions crucial for distinct components of adaptative behaviors, in particular, rostral prefrontal cortex. PMID- 22095218 TI - Long-Term Assessment of Asenapine vs. Olanzapine in Patients with Schizophrenia or Schizoaffective Disorder. PMID- 22095219 TI - Sensory neurons of the human brachial plexus: a quantitative study employing optical fractionation and in vivo volumetric magnetic resonance imaging. AB - BACKGROUND: Extensive neuron death following peripheral nerve trauma is implicated in poor sensory recovery. Translational research for experimentally proven neuroprotective drugs requires knowledge of the numbers and distribution of sensory neurons in the human upper limb and a novel noninvasive clinical measure of neuron loss. OBJECTIVE: To compare optical fractionation and volumetric magnetic resonance imaging (MRI) of dorsal root ganglia (DRG) in histological quantification and objective clinical assessment of human brachial plexus sensory neurons. METHODS: Bilateral C5-T1 DRG were harvested from 5 human cadavers for stereological volume measurement and sensory neuron counts (optical fractionator). MRI scans were obtained from 14 healthy volunteers for volumetric analysis of C5-T1 DRG. RESULTS: The brachial plexus is innervated by 425,409 (standard deviation 15,596) sensory neurons with a significant difference in neuron counts and DRG volume between segmental levels (P < .001), with C7 ganglion containing the most. DRG volume correlated with neuron counts (r = 0.75, P < .001). Vertebral artery pulsation hindered C5 and 6 imaging, yet high resolution MRI of C7, C8, and T1 DRG permitted unbiased volume measurement. In accord with histological analysis, MRI confirmed a significant difference between C7, C8, and T1 DRG volume (P < .001), interindividual variability (CV = 15.3%), and sex differences (P = .04). Slight right-left sided disparity in neuron counts (2.5%, P = .04) was possibly related to hand dominance, but no significant volume disparity existed. CONCLUSION: Neuron counts for the human brachial plexus are presented. These correlate with histological DRG volumes and concur with volumetric MRI results in human volunteers. Volumetric MRI of C7-T1 DRG is a legitimate noninvasive proxy measure of sensory neurons for clinical study. PMID- 22095220 TI - Barrier-limited multimodality closure for reconstruction of wide sellar openings. AB - BACKGROUND: Obtaining a watertight reconstruction with a fat graft with wide sellar exposures can be challenging, including the risk of reinstating mass effect with the fat graft. The alternative, a vascularized pedicle nasoseptal flap, may require several days to heal and still has a > 5% cerebrospinal fluid (CSF) leak rate. OBJECTIVE: To assess the efficacy of a barrier-limited multimodality (BLMM) closure, consisting of an autograft fat-based watertight seal and limited by a membrane barrier, together with the vascularized nasoseptal flap. METHODS: This is a retrospective review of 27 consecutive patients undergoing endonasal cranial base surgery limited to the sellar-parasellar region at the UCLA Medical Center who experienced an intraoperative CSF leak that was repaired with the BLMM technique. The results of 43 prior case-controlled reconstructions using a nasoseptal flap, without the full BLMM technique, were analyzed as a comparison group. RESULTS: There were no postoperative CSF leaks in the patients reconstructed with the BLMM closure technique. The CSF leak rate for the comparison group receiving nasoseptal flaps was 19%. CONCLUSION: A BLMM closure may further decrease the incidence of postoperative CSF leaks compared with predominant reliance on a nasoseptal flap. The novel membrane barrier allows a watertight inner closure by preventing herniation of the fat autograft into the resection cavity. An outer-layer nasoseptal flap provides a living barrier for optimal long-term defense. PMID- 22095221 TI - Long-term clinical and angiographic results of Neuroform stent-assisted coil embolization in wide-necked intracranial aneurysms. AB - BACKGROUND: Neuroform stent-assisted coil embolization facilitates the endovascular treatment of wide-necked intracranial aneurysms. However, the safety and efficacy of its long-term use have not been fully elucidated. OBJECTIVE: To retrospectively examine the long-term results of Neuroform stent usage in conjunction with coil embolization in wide-necked intracranial aneurysms. METHODS: Between November 2002 and December 2010, 79 patients harboring wide necked intracranial aneurysms were treated with use of the Neuroform stent. The stenting procedure failed in 2 patients. Therefore, 77 patients harboring 79 intracranial aneurysms were included for analysis. Patient and aneurysm characteristics, progression of aneurysm occlusion, and occurrence of complications were analyzed. Follow-up imaging included digital subtraction angiography (DSA) or magnetic resonance angiography (MRA). Kaplan-Meier analysis, as well as univariate analysis were performed to determine the progression of aneurysm occlusion and to examine the predictive factors for complete aneurysm occlusion, respectively. RESULTS: Overall, complete aneurysm occlusion was observed in 42.4% of the cases immediately after treatment and progressed to 96.5% at 7-year follow-up. The mean angiographic follow-up time was 25.8 months (range, 0-84 months). Eleven aneurysms (14%) were re-treated. Sixty-eight patients (88.3%) had favorable clinical outcome with a modified Rankin Scale (mRS) <= 1, 3 patients (3.9%) had an mRS of 2, and 5 patients (6.5%) did not have a clinical follow-up. The mean clinical follow-up time was 45.4 months (range, 3 92 months). One patient (1.3%) died of a procedure-related hemorrhage. CONCLUSION: Neuroform stent-assisted coil embolization of wide-necked intracranial aneurysms prevents hemorrhage and provides a high rate of aneurysm occlusion at long-term follow-up. PMID- 22095222 TI - PTEN and PIK3CA gene copy numbers and poor outcomes in non-small cell lung cancer patients with gefitinib therapy. AB - METHODS: Fluorescent in situ hybridisation analyses of PTEN, PIK3CA, EGFR and CEN7 were performed on tumour specimens from patients treated on the expanded access gefitinib trial. Progression-free survival (PFS) and overall survival (OS) were correlated with outcomes in all patients and EGFR wild-type patients. RESULTS: Progression-free survival (hazard ratio=2.54, P<0.001) and OS (hazard ratio=4.04, P<0.001) were significantly shorter in patients whose tumours had all of the following molecular patterns: CEN7 <4 copies per cell, PTEN loss (<2 copies in at least 20% of cells), and PIK3CA gain (>2 copies in at least 40% of cells) both in all and EGFR wild-type only patients. CONCLUSION: The combination of low CEN7 copy number, PTEN loss, and PI3KCA gain may be useful for identifying NSCLC patients unlikely to benefit from treatment with EGFR (TKIs), specifically in wild-type EGFR cases. PMID- 22095223 TI - Cancer risk by combined levels of YKL-40 and C-reactive protein in the general population. AB - BACKGROUND: YKL-40 and C-reactive protein (CRP) are biomarkers that may reflect cancer-related subclinical inflammation. We assessed elevated YKL-40 and CRP levels as combined risk predictors for cancer. METHODS: We measured plasma YKL-40 and CRP at baseline in 8706 individuals from the Danish general population. RESULTS: Hazard ratio (HR) of gastrointestinal cancer for a doubling of YKL-40 levels was 1.37 (95% CI: 1.17-1.61) and indifferent to adjustment for CRP levels. Hazard ratio of lung cancer for a doubling of CRP levels was 1.35 (1.17-1.56) and indifferent to adjustment for YKL-40 levels. Compared to individuals with both low CRP (<1.7 mg l(-1)) and YKL-40 (<154 MUg l(-1)), individuals with high YKL-40 but low CRP had an HR of gastrointestinal cancer of 3.36 (1.70-6.64), whereas individuals with high CRP but low YKL-40 had an HR of lung cancer of 2.19 (1.24 3.87). The area under the receiver operating characteristic (ROC) curve was 0.68 for the ability of YKL-40 to predict gastrointestinal cancer and 0.67 for the ability of CRP to predict lung cancer. CONCLUSION: Elevated YKL-40 levels are associated with increased risk of gastrointestinal cancer, independently of CRP levels, whereas elevated CRP levels are associated with increased risk of lung cancer, independently of YKL-40 levels. PMID- 22095224 TI - Dissecting the expression of EEF1A1/2 genes in human prostate cancer cells: the potential of EEF1A2 as a hallmark for prostate transformation and progression. AB - BACKGROUND: In prostate adenocarcinoma, the dissection of the expression behaviour of the eukaryotic elongation factors (eEF1A1/2) has not yet fully elucidated. METHODS: The EEF1A1/A2 expressions were investigated by real-time PCR, western blotting (cytoplasmic and cytoskeletal/nuclear-enriched fractions) and immunofluorescence in the androgen-responsive LNCaP and the non-responsive DU 145 and PC-3 cells, displaying a low, moderate and high aggressive phenotype, respectively. Targeted experiments were also conducted in the androgen-responsive 22Rv1, a cell line marking the progression towards androgen-refractory tumour. The non-tumourigenic prostate PZHPV-7 cell line was the control. RESULTS: Compared with PZHPV-7, cancer cells showed no major variations in EEF1A1 mRNA; eEF1A1 protein increased only in cytoskeletal/nuclear fraction. On the contrary, a significant rise of EEF1A2 mRNA and protein were found, with the highest levels detected in LNCaP. Eukaryotic elongation factor 1A2 immunostaining confirmed the western blotting results. Pilot evaluation in archive prostate tissues showed the presence of EEF1A2 mRNA in near all neoplastic and perineoplastic but not in normal samples or in benign adenoma; in contrast, EEF1A1 mRNA was everywhere detectable. CONCLUSION: Eukaryotic elongation factor 1A2 switch-on, observed in cultured tumour prostate cells and in human prostate tumour samples, may represent a feature of prostate cancer; in contrast, a minor involvement is assigned to EEF1A1. These observations suggest to consider EEF1A2 as a marker for prostate cell transformation and/or possibly as a hallmark of cancer progression. PMID- 22095225 TI - Expression of Y-box-binding protein YB-1 allows stratification into long- and short-term survivors of head and neck cancer patients. AB - BACKGROUND: Histology-based classifications and clinical parameters of head and neck squamous cell carcinoma (HNSCC) are limited in their clinical capacity to provide information on prognosis and treatment choice of HNSCC. The primary aim of this study was to analyse Y-box-binding protein-1 (YB-1) protein expression in different grading groups of HNSCC patients, and to correlate these findings with the disease-specific survival (DSS). METHODS: We investigated the expression and cellular localisation of the oncogenic transcription/translation factor YB-1 by immunohistochemistry on tissue micro arrays in a total of 365 HNSCC specimens and correlated expression data with clinico-pathological parameters including DSS. RESULTS: Compared with control tissue from healthy individuals, a significantly (P<0.01) increased YB-1 protein expression was observed in high-grade HNSCC patients. By univariate survival data analysis, HNSCC patients with elevated YB-1 protein expression had a significantly (P<0.01) decreased DSS. By multivariate Cox regression analysis, high YB-1 expression and nuclear localisation retained its significance as a statistically independent (P<0.002) prognostic marker for DSS. Within grade 2 group of HNSCC patients, a subgroup defined by high nuclear and cytoplasmic YB-1 levels (co-expression pattern) in the cells of the tumour invasion front had a significantly poorer 5-year DSS rate of only 38% compared with overall 55% for grade 2 patients. Vice versa, the DSS rate was markedly increased to 74% for grade 2 cancer patients with low YB-1 protein expression at the same localisation. CONCLUSION: Our findings point to the fact that YB-1 expression in combination with histological classification in a double stratification strategy is superior to classical grading in the prediction of tumour progression in HNSCC. PMID- 22095226 TI - Distinct association between aberrant methylation of Wnt inhibitors and genetic alterations in acute myeloid leukaemia. AB - BACKGROUND: Aberrant activation of Wnt signalling through hypermethylation of Wnt inhibitor genes is involved in several human malignancies, including acute myeloid leukaemia (AML). It remains unclear whether hypermethylation of Wnt inhibitors is associated with molecular gene mutations in the development of AML. METHODS: We investigated the association of the promoter hypermethylation of six Wnt inhibitors (Wif-1, SFRP1, SFRR2, SFRP4, SFRP5, and DKK1) with gene aberrations in the leukaemogenesis of 269 AML patients. RESULTS: In total, 166 patients (61.7%) had hypermethylation of at least one Wnt inhibitor. The majority (68.5%) of patients with Wnt inhibitor hypermethylation had concurrent Class II gene mutations that affect transcription factors or cofactors. There was a close association of Wif-1 hypermethylation with t(15;17) (P=0.0005) and CEBPA mutation (P<0.0001), DKK1 hypermethylation with t(8;21) (P<0.0001) and ASXL1 mutation (P=0.0078), SFRP-1 hypermethylation with t(8;21) (P<0.0001), SFRP-2 hypermethylation with AML1/RUNX1 mutation (P=0.0012), and SFRP-5 hypermethylation with MLL/PTD (P=0.0505). On the other side, hypermethylation of Wnt inhibitors was always negatively associated with NPM1 mutation and FLT3/ITD. CONCLUSION: There was distinct association between hypermethylation of individual Wnt inhibitors and specific gene aberrations, especially Class II mutations. The Wnt inhibitor hypermethylation might interact with genetic alterations in the leukaemogenesis. PMID- 22095227 TI - Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis. AB - BACKGROUND: Molecular characterisation using gene-expression profiling will undoubtedly improve the prediction of treatment responses, and ultimately, the clinical outcome of cancer patients. METHODS: To establish the procedures to identify responders to FOLFOX therapy, 83 colorectal cancer (CRC) patients including 42 responders and 41 non-responders were divided into training (54 patients) and test (29 patients) sets. Using Random Forests (RF) algorithm in the training set, predictor genes for FOLFOX therapy were identified, which were applied to test samples and sensitivity, specificity, and out-of-bag classification accuracy were calculated. RESULTS: In the training set, 22 of 27 responders (81.4% sensitivity) and 23 of 27 non-responders (85.1% specificity) were correctly classified. To improve the prediction model, we removed the outliers determined by RF, and the model could correctly classify 21 of 23 responders (91.3%) and 22 of 23 non-responders (95.6%) in the training set, and 80.0% sensitivity and 92.8% specificity, with an accuracy of 69.2% in 29 independent test samples. CONCLUSION: Random Forests on gene-expression data for CRC patients was effectively able to stratify responders to FOLFOX therapy with high accuracy, and use of pharmacogenomics in anticancer therapy is the first step in planning personalised therapy. PMID- 22095228 TI - Severe clinical toxicities are correlated with survival in patients with advanced renal cell carcinoma treated with sunitinib and sorafenib. AB - BACKGROUND: In advanced renal cell carcinoma (RCC), sunitinib and sorafenib tyrosine kinase inhibitors (TKI) are associated with several clinical side effects, with no definitive established data concerning their clinical impact. METHODS: From June 2006 to June 2008, main clinical TKI-induced toxicities, including digestive, cardiac, dermatologic and asthenia were retrospectively collected using the NCI-CTC version 3.0 in patients treated with TKI for an RCC. RESULTS: The median overall survival was significantly improved in patients with grade 3-4 clinical toxicities (36 vs 12 months, P=0.009). In multivariate analysis, the Memorial Sloan-Kettering Cancer Center risk groups (good vs intermediate or poor) and clinical toxicities (grade 3-4 vs 1-2) were identified as independent prognostic factors of better survival (P=0.002 and P=0.02, respectively). The Charlson comorbidity index score (>7 vs <7) was identified as independent predictive factor of severe clinical TKI-induced toxicities (P=0.02). CONCLUSION: In this unselected patients of RCC, clinical TKI-related severe toxicities were more frequent in patients with comorbidities and were associated with better survival. PMID- 22095229 TI - Correlates of anti-EBV EBNA1 IgA positivity among unaffected relatives from nasopharyngeal carcinoma multiplex families. AB - BACKGROUND: To determine whether non-viral nasopharyngeal carcinoma (NPC) risk factors might be associated with (and mediated through) Epstein-Barr virus (EBV) serological responses linked to NPC risk, we evaluated predictors of risk of anti EBNA1 IgA seropositivity and other markers among unaffected relatives from a large NPC family study in Taiwan. METHODS: Multivariate logistic regression conditioned on family was used to examine the associations between sociodemographic, dietary, lifestyle, and occupational variables and risk of anti EBV EBNA1 IgA positivity, anti-VCA IgA, and anti-DNase positivity. RESULTS: Among 2393 unaffected relatives from 319 multiplex families, 1180 (49.3%) were anti-EBV EBNA1 IgA seropositive. None of the associations with anti-EBNA1 IgA were statistically significant, except for being 31-50 years of age (vs <30, adjusted ORs 0.51-0.57). For one or more EBV serological markers, there were suggestive associations for older age, GuangDong firm salted fish, betel use, current alcohol use, and male gender. CONCLUSION: Overall, we found little evidence to suggest that non-viral NPC risk factors significantly alter EBV serological patterns, suggesting that non-viral NPC risk factors act through pathways independent of EBV serological responses. PMID- 22095230 TI - High basal NF-kappaB activity in nonpigmented melanoma cells is associated with an enhanced sensitivity to vitamin D3 derivatives. AB - BACKGROUND: Melanoma is highly resistant to current modalities of therapy, with the extent of pigmentation playing an important role in therapeutic resistance. Nuclear factor-kappaB (NF-kappaB) is constitutively activated in melanoma and can serve as a molecular target for cancer therapy and steroid/secosteroid action. METHODS: Cultured melanoma cells were used for mechanistic studies on NF-kappaB activity, utilising immunofluorescence, western blotting, EMSA, ELISA, gene reporter, and estimated DNA synthesis assays. Formalin-fixed, paraffin-embedded specimens from melanoma patients were used for immunocytochemical analysis of NF kappaB activity in situ. RESULTS: Novel 20-hydroxyvitamin (20(OH)D(3)) and classical 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) secosteroids inhibited melanoma cell proliferation. Active forms of vitamin D were found to inhibit NF-kappaB activity in nonpigmented cells, while having no effect on pigmented cells. Treatment of nonpigmented cells with vitamin D3 derivatives inhibited NF-kappaB DNA binding and NF-kappaB-dependent reporter assays, as well as inhibited the nuclear translocation of the p65 NF-kappaB subunit and its accumulation in the cytoplasm. Moreover, analysis of biopsies of melanoma patients showed that nonpigmented and slightly pigmented melanomas displayed higher nuclear NF-kappaB p65 expression than highly pigmented melanomas. CONCLUSION: Classical 1,25(OH)(2)D(3) and novel 20(OH)D(3) hydroxyderivatives of vitamin D3 can target NF-kappaB and regulate melanoma progression in nonpigmented melanoma cells. Melanin pigmentation is associated with the resistance of melanomas to 20(OH)D(3) and 1,25(OH)(2)D(3) treatment. PMID- 22095231 TI - PET imaging of patients with non-small cell lung cancer employing an EGF receptor targeting drug as tracer. AB - BACKGROUND: We have previously developed (11)C-erlotinib as a new positron emission tomography (PET) tracer and shown that it accumulates in epidermal growth factor receptor (EGFR)-positive lung cancer xenografts in mice. Here, we present a study in patients with non-small cell lung cancer (NSCLC) investigating the feasibility of (11)C-erlotinib PET as a potential method for the identification of lung tumours accumulating erlotinib. METHODS: Thirteen patients with NSCLC destined for erlotinib treatment were examined by contrast-enhanced computed tomography (CT), (11)C-erlotinib PET/low-dose CT and (18)F-fluoro-2 deoxy-D-glucose ((18)F-FDG) PET/low-dose CT before start of the erlotinib treatment. After 12 weeks treatment, they were examined by (18)F-FDG PET/contrast enhanced CT for the assessment of clinical response. RESULTS: Of the 13 patients included, 4 accumulated (11)C-erlotinib in one or more of their lung tumours or lymph-node metastases. Moreover, (11)C-erlotinib PET/CT identified lesions that were not visible on (18)F-FDG PET/CT. Of the four patients with accumulation of (11)C-erlotinib, one died before follow-up, whereas the other three showed a positive response to erlotinib treatment. Three of the nine patients with no accumulation died before follow-up, four showed progressive disease while two had stable disease after 12 weeks of treatment. CONCLUSION: Our data show a potential for (11)C-erlotinib PET/CT for visualizing NSCLC lung tumours, including lymph nodes not identified by (18)F-FDG PET/CT. Large clinical studies are now needed to explore to which extent pre-treatment (11)C-erlotinib PET/CT can predict erlotinib treatment response. PMID- 22095232 TI - Disease stage predicts post-diagnosis anxiety and depression only in some types of cancer. AB - BACKGROUND: We hypothesised that patients with advanced disease or a cancer type that has a poor prognosis may be more likely to report anxiety and depressive symptoms after diagnosis; younger age and female gender may moderate these effects. METHODS: Patients (n=3850) were consecutively assessed with PSSCAN, a standardised, validated tool, at two large cancer centres between 2004 and 2009. RESULTS: Female patients reported more anxiety and depressive symptoms (P=0.003 to P<0.001) compared with men and a healthy comparison group. Older age was associated with fewer anxiety (P=0.033 to P<0.001) and fewer depressive symptoms (P<0.001), but this was not true for lung cancer. Presence of metastases was associated with more anxiety symptoms in patients with gastrointestinal (P=0.044; R(2)Delta=0.001), lung (P=0.011; R(2)Delta=0.016), and prostate (P=0.032; R(2)Delta=0.008) cancer, but this was not true for breast cancer. Furthermore, early disease stage was associated with fewer depressive symptoms among older prostate cancer patients (P=0.021; R(2)Delta=0.008). Men with early lung cancer reported fewer anxiety (P=0.020; R(2)Delta=0.013) and depressive (P=0.017; R(2)Delta=0.016) symptoms than men with advanced disease or women. CONCLUSION: As hypothesised, disease stage was directly associated with emotional distress, except for patients with breast cancer. Furthermore, age and gender moderated some of these effects. PMID- 22095233 TI - Expression of p16INK4a, alone or combined with p53, is predictive of better prognosis in colorectal adenocarcinoma in Tunisian patients. AB - INTRODUCTION: Alterations in different signaling pathways are involved in initiation and progression of colorectal carcinoma, such as those related to p53, MLH1, p16INK4a, Kras, etc. AIM: This study was conducted with the aim to investigate the expression of p16INK4a and p53 in colorectal cancer (CRC) and evaluated their correlation with major clinicopathologic features and patients' survival. MATERIALS AND METHODS: The expression of p16INK4a and p53 were analyzed by immunohistochemistry on 70 paraffin specimens of CRC. RESULTS: Positive immunostaining for p16INK4a and p53 was observed in 27 (38.6%) and 53 (80%) cases, respectively. Significant correlation between loss of p16INK4a expression and tumor size was found (P=0.008), whereas overexpression of p16INK4a correlated with favorable prognosis parameters, such as absence of lymph node metastasis (P=0.029) and early stage of CRC (P=0.027). Furthermore, p53 overexpression significantly correlated with distal tumor location (P=0.022) and was related to a better overall survival in the group of patients with distal colon carcinomas (P=0.002). Patients with p16INK4a-positive tumors had a significant longer overall survival time than patients with p16INK4a-negative carcinomas (P=0.033). In addition, Cox regression model showed that overexpression of p16INK4a is an independent factor for prognosis with depth of invasion, p53 accumulation, and coincident abnormal expression of p16INK4a or p53. CONCLUSION: Our data suggest that the assessment of both p53 and p16INK4a expression might be helpful in predicting prognosis in patients with colorectal cancer. PMID- 22095234 TI - Early insulin therapy prevents beta cell loss in a mouse model for permanent neonatal diabetes (Munich Ins2(C95S)). AB - AIMS: Heterozygous male Munich Ins2(C95S) mutant mice, a model for permanent neonatal diabetes mellitus, demonstrate a progressive diabetic phenotype with severe loss of functional beta cell mass. The aim of this study was to investigate the influence of early insulin treatment on glucose homeostasis and beta cell destruction in male Munich Ins2(C95S) mutants. METHODS: One group of male Ins2(C95S) mutants was treated with subcutaneous insulin pellets, as soon as blood glucose levels began to rise; placebo-treated mutants and wild-type mice served as controls. An additional group of mutant mice received a sodium dependent glucose transporter 2 (SGLT2) inhibitor (AVE2268) via rodent chow. RESULTS: Insulin treatment normalised blood glucose concentrations, improved oral glucose tolerance, preserved insulin sensitivity and inhibited oxidative stress of Munich Ins2(C95S) mutant mice. Pancreatic C-peptide content, as well as total beta cell and isolated beta cell volumes, of insulin-treated mutant mice were higher than those of placebo-treated mutants. In addition, alpha cell dysfunction and hyperplasia of non-beta cells were completely normalised in insulin-treated mutant mice. Treatment with the SGLT2 inhibitor lowered blood glucose, improved glucose tolerance and normalised insulin sensitivity as well as oxidative stress of Ins2(C95S) mutants. The abundance of the endoplasmic reticulum (ER) stress markers binding Ig protein (BiP) and phosphorylated eukaryotic translation initiation factor 2 alpha (P-eIF2alpha) was significantly increased in the islets of mutants, before onset of hyperglycaemia, vs wild-type mice. CONCLUSIONS: We conclude that early insulin treatment protects Munich Ins2(C95S) mutant mice from insulin resistance, alpha cell hyperfunction, beta cell loss and hyperplasia of non-beta cells, some well-known features of human diabetes mellitus. Therefore, insulin treatment may be considered early for human patients harbouring INS mutations. PMID- 22095235 TI - Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob/ob mice. AB - AIMS/HYPOTHESIS: Arctigenin is a natural compound that had never been previously demonstrated to have a glucose-lowering effect. Here it was found to activate AMP activated protein kinase (AMPK), and the mechanism by which this occurred, as well as the effects on glucose and lipid metabolism were investigated. METHODS: 2 Deoxyglucose uptake and AMPK phosphorylation were examined in L6 myotubes and isolated skeletal muscle. Gluconeogenesis and lipid synthesis were evaluated in rat primary hepatocytes. The acute and chronic effects of arctigenin on metabolic abnormalities were observed in C57BL/6J and ob/ob mice. Changes in mitochondrial membrane potential were measured using the J-aggregate-forming dye, JC-1. Analysis of respiration of L6 myotubes or isolated mitochondria was conducted in a channel oxygen system. RESULTS: Arctigenin increased AMPK phosphorylation and stimulated glucose uptake in L6 myotubes and isolated skeletal muscles. In primary hepatocytes, it decreased gluconeogenesis and lipid synthesis. The enhancement of glucose uptake and suppression of hepatic gluconeogenesis and lipid synthesis by arctigenin were prevented by blockade of AMPK activation. The respiration of L6 myotubes or isolated mitochondria was inhibited by arctigenin with a specific effect on respiratory complex I. A single oral dose of arctigenin reduced gluconeogenesis in C57BL/6J mice. Chronic oral administration of arctigenin lowered blood glucose and improved lipid metabolism in ob/ob mice. CONCLUSIONS/INTERPRETATION: This study demonstrates a new role for arctigenin as a potent indirect activator of AMPK via inhibition of respiratory complex I, with beneficial effects on metabolic disorders in ob/ob mice. This highlights the potential value of arctigenin as a possible treatment of type 2 diabetes. PMID- 22095236 TI - Elevated levels of renal and circulating Nop-7-associated 2 (NSA2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy. AB - AIMS/HYPOTHESIS: We previously found that Nop-7-associated 2 (NSA2), which is involved in ribosomal biogenesis in yeast and is a putative cell cycle regulator in mammalian cells, is elevated in the kidney of Goto-Kakizaki (GK) rat, a spontaneous model of type 2 diabetes. Here we tested the hypothesis that elevated NSA2 is involved in diabetic nephropathy (DN). METHODS: We examined Nsa2/NSA2 expression and NSA2 production in two rodent models of diabetes, in cultured renal glomerular cells, and in diabetic patients with and without nephropathy. Patients with nephropathy who had a history of albuminuria were further divided as responders (DN-NA; DN patients normoalbuminuric at the time of this study with a history of albuminuria) and non-responders (DN-A; diabetic nephropathy patients with albuminuria) to current treatment for albuminuria. RESULTS: Renal Nsa2/NSA2 mRNA increased in tandem with hyperglycaemia in GK rats, in a streptozotocin induced mouse model of diabetes, and in human mesangial cells (HMCs) grown in high glucose (p < 0.05). In the mouse model of diabetes, hyperglycaemia resulted in increased Nsa2 expression and NSA2 levels in tubular and glomerular cells and in circulating cells; this increase was normalised by diabetes treatment. Circulating NSA2 mRNA levels were elevated in patients with DN independently of body weight (BMI), glycaemic (HbA(1c)) and haemodynamic (blood pressure) control, and showed an inverse correlation with renal function (GFR, p < 0.05). NSA2 levels were the only variable that showed a significant difference between patients with albuminuria (DN-A) compared with non-albuminuric patients (DN-NA) and diabetic controls (p < 0.05), this increase being independent of all other variables, including GFR. CONCLUSION: We show for the first time that renal and circulating NSA2/NSA2 levels are increased in hyperglycaemia in experimental models of diabetes, and that circulating NSA2 is elevated in DN patients with albuminuria. Further studies will be required to assess whether NSA2 plays a role in the pathogenesis of DN. PMID- 22095238 TI - An important minority of prediabetic first-degree relatives of type 1 diabetic patients derives from seroconversion to persistent autoantibody positivity after 10 years of age. AB - AIMS/HYPOTHESIS: The appearance of autoantibodies (Abs) before diabetes onset has mainly been studied in young children. However, most patients develop type 1 diabetes after the age of 15 years. In first-degree relatives aged under 40 years, we investigated the frequency of seroconversion to (persistent) Ab positivity, progression to diabetes and baseline characteristics of seroconverters according to age. METHODS: Abs against insulin (IAA), glutamate decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and zinc transporter 8 (ZnT8A) were measured during follow-up of 7,170 first-degree relatives. RESULTS: We identified 379 (5.3%) relatives with positivity for IAA, GADA, IA-2A and/or ZnT8A (Ab(+)) at first sampling and 224 (3.1%) at a later time point. Most seroconversions occurred after the age of 10 years (63%). During follow-up, Abs persisted more often in relatives initially Ab(+) (76%) than in seroconverters (53%; p < 0.001). In both groups diabetes developed at a similar pace and almost exclusively with Ab persistence (136 of 139 prediabetic individuals). For both groups, progression was more rapid if Abs appeared before the age of 10 years. Baseline characteristics at seroconversion did not vary significantly according to age. CONCLUSIONS/INTERPRETATION: Seroconversion to (persistent) Ab(+) occurs regardless of age. Although the progression rate to diabetes is higher under age 10 years, later seroconverters (up to age 40 years) have similar characteristics when compared with age-matched initially Ab(+) relatives and generate an important minority of prediabetic relatives, warranting their identification and, eventually, enrolment in prevention trials. PMID- 22095239 TI - Common variation in oxidative phosphorylation genes is not a major cause of insulin resistance or type 2 diabetes. AB - AIMS/HYPOTHESIS: There is substantial evidence that mitochondrial dysfunction is linked to insulin resistance and is present in several tissues relevant to the pathogenesis of type 2 diabetes. Here, we examined whether common variation in genes involved in oxidative phosphorylation (OxPhos) contributes to type 2 diabetes susceptibility or influences diabetes-related metabolic traits. METHODS: OxPhos gene variants (n = 10) that had been nominally associated (p < 0.01) with type 2 diabetes in a recent genome-wide meta-analysis (n = 10,108) were selected for follow-up in 3,599 type 2 diabetic and 4,956 glucose-tolerant Danish individuals. A meta-analysis of these variants was performed in 11,729 type 2 diabetic patients and 43,943 non-diabetic individuals. The impact on OGTT-derived metabolic traits was evaluated in 5,869 treatment-naive individuals from the Danish Inter99 study. RESULTS: The minor alleles of COX10 rs9915302 (p = 0.02) and COX5B rs1466100 (p = 0.005) showed nominal association with type 2 diabetes in our Danish cohort. However, in the meta-analysis, none of the investigated variants showed a robust association with type 2 diabetes after correction for multiple testing. Among the alleles potentially associated with type 2 diabetes, none negatively influenced surrogate markers of insulin sensitivity in non diabetic participants, while the minor alleles of UQCRC1 rs2228561 and COX10 rs10521253 showed a weak (p < 0.01 to p < 0.05) negative influence on indices of glucose-stimulated insulin secretion. CONCLUSIONS/INTERPRETATION: We cannot rule out the possibility that common variants in or near OxPhos genes may influence beta cell function in non-diabetic individuals. However, our quantitative trait studies and a sufficiently large meta-analysis indicate that common variation in proximity to the examined OxPhos genes is not a major cause of insulin resistance or type 2 diabetes. PMID- 22095241 TI - Sucrose phosphate phosphatase in the green alga Klebsormidium flaccidum (Streptophyta) lacks an extensive C-terminal domain and differs from that of land plants. AB - Previously, it was reported that like land plants, the green alga Klebsormidium flaccidum (Streptophyta) accumulates sucrose during cold acclimation (Nagao et al. Plant Cell Environ 31:872-885, 2008), suggesting that synthesis of sucrose could enhance the freezing tolerance of this alga. Because sucrose phosphate phosphatase (SPP; EC 3.1.3.24) is a key enzyme in the sucrose synthesis pathway in plants, we analyzed the SPP gene in K. flaccidum (KfSPP, GenBank accession number AB669024) to clarify its role in sucrose accumulation. As determined from its deduced amino acid sequence, KfSPP contains the N-terminal domain that is characteristic of the L-2-haloacid-dehalogenase family of phosphatases/hydrolases (the HAD phosphatase domain). However, it lacks the extensive C-terminal domain found in SPPs of land plants. Database searches revealed that the SPPs in cyanobacteria also lack the C-terminal domain. In addition, the green alga Coccomyxa (Chlorophyta) and K. flaccidum, which are closely related to land plants, have cyanobacterial-type SPPs, while Chlorella (Chlorophyta) has a land plant-type SPP. These results demonstrate that even K. flaccidum (Streptophyta), as a recent ancestor of land plants, has the cyanobacterial-type SPP lacking the C-terminal domain. Because SPP and sucrose phosphate synthase (SPS) catalyze sequential reactions in sucrose synthesis in green plant cells and the lack of the C-terminal domain in KfSPP is predicted to decrease its activity, the interaction between decreased KfSPP activity and SPS activity may alter sucrose synthesis during cold acclimation in K. flaccidum. PMID- 22095243 TI - A kinetics and mechanistic study on the role of the structural rigidity of the linker on the substitution reactions of chelated dinuclear Pt(II) complexes. AB - Substitution reactions of platinum complexes bearing cyclohexylamine/diamine moieties viz., [Pt(H(2)O)(N,N-bis(2 pyridylmethyl)cyclohexylamine)](CF(3)SO(3))(2), bpcHna; [{Pt(H(2)O)}(2)(N,N,N',N' tetrakis(2-pyridylmethyl)-trans-1,4-cyclohexyldiamine)](CF(3)SO(3))(4), cHn and [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-4,4' dicyclohexylmethanediamine)](CF(3)SO(3))(4), dcHnm and phenylamine/diamine moieties viz., ([Pt(H(2)O)N,N-bis(2-pyridylmethyl)phenylamine)](CF(3)SO(3))(2), bpPha; [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-1,3 phenyldiamine)](CF(3)SO(3))(4), mPh; [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2 pyridylmethyl)-1,4-phenyldiamine)](CF(3)SO(3))(4), pPh and [{Pt(H(2)O)}(2)(N,N,N',N'-tetrakis(2-pyridylmethyl)-4,4' diphenylmethanediamine)](CF(3)SO(3))(4)), dPhm with thiourea nucleophiles were studied in acidified 0.01 M LiCF(3)SO(3) aqueous medium under pseudo-first-order conditions using stopped-flow and UV-visible spectrophotometric techniques. The rate of substitution follows a similar trend in the two sets of complexes and decreases in the order: bpcHna > dcHnm > cHn and bpPha > dPhm ~ pPh ~ mPh), respectively. The result of this study has shown that the rigidity and/or the planarity of a diamine bridge linking the two (2-pyridylmethyl)amine-chelated Pt(II) centres, influences the reactivity of the metal centres by protracting similar symmetry elements within the complexes, which determines the amount of steric influences felt on the coordination square-plane. Hence, the order of reactivity is controlled by both the steric hindrance and the magnitude of the trans sigma-inductive effect originating from the linker towards the metal centre. These two factors also impact on the acidity of the complexes. The high negative entropies and low positive enthalpies support an associative mode of activation. PMID- 22095242 TI - Heparin inhibits the interaction of DNA topoisomerase I/anti-topoisomerase I immune complexes with heparan sulfate on dermal fibroblasts. AB - OBJECTIVE: Previous studies have demonstrated that the systemic sclerosis (SSc) associated autoantigen DNA topoisomerase I (topo I) binds specifically to the surface of fibroblasts when released in the extracellular environment and recruits anti-topo I autoantibodies, which subsequently leads to the adhesion and activation of monocytes. This study aimed to characterize the molecular interactions of topo I with fibroblast surfaces in order to elucidate the pathogenic role of topo I/anti-topo I immune complexes (ICs) in SSc. METHODS: Topo I directly coupled to fluorochromes was used to follow its binding to fibroblast surfaces by flow cytometry and fluorescence microscopy. Purified IgG from normal subjects or SSc patients was added with topo I to the cells; unfractionated heparin (UFH) and low molecular weight heparin (LMWH) were used to determine their effects on the binding of topo I and topo I/anti-topo I IC to fibroblast surfaces. RESULTS: Heparan sulfate (HS) proteoglycans on fibroblast surfaces were found to act as coreceptors for topo I binding. The addition of anti-topo I autoantibodies from SSc sera led to the amplification of topo I binding to HS chains. UFH and LMWH were shown to inhibit topo I and topo I/anti topo I IC binding to HS chains. CONCLUSION: This study is the first to show that topo I binds specifically to HS proteoglycans on fibroblast surfaces and that anti-topo I autoantibodies from SSc patients amplify topo I binding to HS chains. The accumulation of topo I on cell surfaces by anti-topo I autoantibodies could contribute to the initiation of an inflammatory cascade stimulating the fibrosis. UFH and LMWH inhibited the binding of topo I/anti-topo I IC to fibroblasts, suggesting a potential therapeutic role in SSc-associated fibrosis. PMID- 22095240 TI - Molecular basis of Staphylococcus epidermidis infections. AB - Staphylococcus epidermidis is the most important member of the coagulase-negative staphylococci and one of the most abundant colonizers of human skin. While for a long time regarded as innocuous, it has been identified as the most frequent cause of device-related infections occurring in the hospital setting and is therefore now recognized as an important opportunistic pathogen. S. epidermidis produces a series of molecules that provide protection from host defenses. Specifically, many proteins and exopolymers, such as the exopolysaccharide PIA, contribute to biofilm formation and inhibit phagocytosis and the activity of human antimicrobial peptides. Furthermore, recent research has identified a family of pro-inflammatory peptides in S. epidermidis, the phenol-soluble modulins (PSMs), which have multiple functions in immune evasion and biofilm development, and may be cytolytic. However, in accordance with the relatively benign relationship that S. epidermidis has with its host, production of aggressive members of the PSM family is kept at a low level. Interestingly, in contrast to S. aureus with its large arsenal of toxins developed for causing infection in the human host, most if not all "virulence factors" of S. epidermidis appear to have original functions in the commensal lifestyle of this bacterium. PMID- 22095244 TI - Third-line sunitinib following sequential use of cytokine therapy and sorafenib in Japanese patients with metastatic renal cell carcinoma. AB - BACKGROUND: The aim of this study was to evaluate the use of sunitinib as third line therapy for metastatic renal cell carcinoma (mRCC). METHODS: This study included a total of 35 consecutive Japanese patients with mRCC who were treated with third-line sunitinib after sequential use of cytokine therapy (interferon alpha and/or interleukin-2) and sorafenib between September 2008 and December 2010. The clinical outcomes of third-line sunitinib in these patients were retrospectively reviewed. RESULTS: Of the 35 patients, 3 (8.6%), 28 (80.0%) and 4 (11.4%) were judged to have a partial response, stable disease and progressive disease, respectively, as the best response to sunitinib. The median progression free survival (PFS) and overall survival (OS) of these patients following the introduction of sunitinib were 10.9 and 14.2 months, respectively. Of several factors examined, response to sorafenib and performance status appeared to be independently associated with PFS and OS, respectively, on multivariate analyses. The common grade 3-4 adverse events related to third-line sunitinib were thrombocytopenia (51.4%), neutropenia (42.9%) and hypertension (14.3%). CONCLUSION: Despite the low response rate, third-line sunitinib is well tolerated and could provide comparatively favorable prognostic outcomes in Japanese patients with mRCC after first-line cytokine therapy and second-line sorafenib; therefore, treatment with sunitinib could be one on the therapeutic options for patients with mRCC even after the failure of sequentially performed systemic therapies, such as cytokine therapy and sorafenib. PMID- 22095247 TI - Cervical stromal involvement can predict survival in advanced endometrial carcinoma: a review of 67 patients. AB - PURPOSE: To assess clinical, surgical and pathologic variables in survival of advanced endometrial cancer. METHODS: Sixty-seven advanced-stage (stages III and IV according to FIGO 2009) endometrial cancer cases were evaluated retrospectively. The effects on survival of age, histologic subtype, stage, grade, myometrial invasion, optimal cytoreduction, parity and cervical involvement were analyzed. RESULTS: Cervical involvement (P = 0.033) and nulliparity (P = 0.042) were worsening features in terms of survival. In 56 cases (83.5%) optimal cytoreduction could be achieved and survival was significantly longer in this group than the group who were not optimally cytoreduced (mean 30.4 vs. 9.6 months) (P < 0.01). Depth of myometrial invasion, histologic type of tumor, stage, grade, and age younger or older than 60 years were not found to be related to survival. Neither adjuvant therapy type nor their combination were superior to each other for improving survival. CONCLUSIONS: Cervical stromal involvement is a poor prognostic factor in cases of advanced endometrial carcinoma. Further studies are required to describe the effect of different surgical approaches such as radical hysterectomy on survival in the presence of cervical stromal invasion. PMID- 22095246 TI - Could salvage surgery after chemotherapy have clinical impact on cancer survival of patients with metastatic urothelial carcinoma? AB - BACKGROUND: The clinical impact of salvage surgery after chemotherapy on cancer survival of patients with metastatic urothelial carcinoma is controversial. We aimed to verify the clinical role of salvage surgery by analyzing the long-term outcome in patients with urothelial carcinoma treated by chemotherapy. METHODS: Between 2003 and 2010 at a single institution, 31 of 47 patients (66%) with metastatic urothelial carcinoma showed objective responses (CR in 4, PR in 27) after multiple courses of cisplatin/gemcitabine/paclitaxel-based chemotherapy, and a cohort of patients with partial response (PR) were retrospectively enrolled. Twelve (10 male and 2 female, median age 64.0 years) of 27 patients with PR underwent salvage surgeries after the chemotherapy: metastatectomy of residual lesions (10 retroperitoneal lymph nodes, 2 lung), and 6 radical surgeries for primary lesions as well. Progression-free survival and overall patient survival rates were analyzed retrospectively and compared with those of patients without salvage surgery. RESULTS: All 12 patients achieved surgical CR. Pathological findings of metastatic lesions showed viable cancer cells in 3 patients. In univariate analysis, sole salvage surgery affected overall survival in 27 patients with PR to the chemotherapy (P = 0.0037). Progression-free survival and overall survival rates in patients with salvage surgery were better than those in 15 PR patients without the surgery (39.8 vs. 0%, and 71.6 vs. 12.1% at 3 years, P = 0.01032 and 0.01048; log-rank test). CONCLUSIONS: Salvage surgery for patients with residual tumor who achieve partial response to chemotherapy could have a possible impact on cancer survival. PMID- 22095248 TI - Visual spectral sensitivity of photopic juvenile Pacific bluefin tuna (Thunnus orientalis). AB - Although Pacific bluefin tuna is a species that relies on vision, its photopic visual function is not well known; we therefore recorded electroretinograms to investigate photopic spectral sensitivity in juveniles of this species (49-81 days post-hatch; standard length 74-223 mm). The peak spectral sensitivity wavelength was 505 nm. We estimated that two (lambda(max) = 512-515 nm and 423 436 nm) or three (lambda(max) = 512-515 nm, 423-436 nm, and 473 nm) types of cone visual pigments contribute to photopic vision; these spectral sensitivities are adapted to surface water habitats in clear ocean and coastal water. PMID- 22095245 TI - Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase II and III trials. AB - BACKGROUND: Ethnic differences in drug susceptibility and toxicity are a major concern, not only in drug development but also in the clinical setting. We review the toxicity profiles of docetaxel according to dose and ethnicity. METHODS: We analyzed phase II and III clinical trials that included a once-every-3-weeks single-agent docetaxel arm. Logistic regression analysis was applied to identify the significant variables affecting the reported incidence of docetaxel-induced severe neutropenia. RESULTS: Multivariate logistic regression analysis identified studies conducted in Asia [odds ratio (OR) 19.0; 95% confidence interval (95% CI) 3.64-99.0] and docetaxel dose (OR 1.08; 95% CI 1.03-1.13) as independent variables for the incidence of grade 3/4 neutropenia. CONCLUSIONS: There is a significant difference in the incidence of docetaxel-induced severe neutropenia between Asian and non-Asian clinical studies. Physicians and pharmacists should consider ethnic diversity in docetaxel toxicity when interpreting the results of clinical trials. PMID- 22095250 TI - GTG mutation in the start codon of the androgen receptor gene in a family of horses with 64,XY disorder of sex development. AB - Genetic sex in mammals is determined by the sex chromosomal composition of the zygote. The X and Y chromosomes are responsible for numerous factors that must work in close concert for the proper development of a healthy sexual phenotype. The role of androgens in case of XY chromosomal constitution is crucial for normal male sex differentiation. The intracellular androgenic action is mediated by the androgen receptor (AR), and its impaired function leads to a myriad of syndromes with severe clinical consequences, most notably androgen insensitivity syndrome and prostate cancer. In this paper, we investigated the possibility that an alteration of the equine AR gene explains a recently described familial XY, SRY + disorder of sex development. We uncovered a transition in the first nucleotide of the AR start codon (c.1A>G). To our knowledge, this represents the first causative AR mutation described in domestic animals. It is also a rarely observed mutation in eukaryotes and is unique among the >750 entries of the human androgen receptor mutation database. In addition, we found another quiet missense mutation in exon 1 (c.322C>T). Transcription of AR was confirmed by RT-PCR amplification of several exons. Translation of the full-length AR protein from the initiating GTG start codon was confirmed by Western blot using N- and C terminal-specific antibodies. Two smaller peptides (25 and 14 amino acids long) were identified from the middle of exon 1 and across exons 5 and 6 by mass spectrometry. Based upon our experimental data and the supporting literature, it appears that the AR is expressed as a full-length protein and in a functional form, and the observed phenotype is the result of reduced AR protein expression levels. PMID- 22095249 TI - Laboratory exposure of Oreochromis niloticus to crude microcystins (containing microcystin-LR) extracted from Egyptian locally isolated strain (Microcystis aeruginosa Kutzing): biological and biochemical studies. AB - Cyanobacterial blooms exert negative impacts on fisheries and water management authorities. Recently, it has gained global attention, as elevated earth warming and environmental pollution are accelerating algal growth. Oreochromis niloticus (O. niloticus) is a worldwide and the most commonly cultured fish in Egypt. The biological interaction of the living organisms to the surrounding environment must continuously be assessed to predict future effects of the ongoing hazards on fish. The study was designed to examine the possible biological and biochemical response of O. niloticus exposed to different concentrations of microcystins crude extract (containing microcystin-LR). Three equal groups of O. niloticus were assigned for intraperitoneal injection of three different doses: 100, 200, and 400 MUg m(-1) dried aqueous microcystins extract, for 10 days. Clinical, condition factor (K) and hepatosomatic index (HIS) were estimated. Biochemical alterations were evaluated via lipid peroxidation, DNA fragmentation assay and electrophoretic analysis of fragmented DNA using agarose gel electrophoresis. The results showed that there were discernible behavioral and clinical alterations. Significant differences in K and HIS were observed between treatments. Also, significant elevations were observed in lipid peroxidation level and in the DNA fragmentation percentage in the exposed fish to the doses of 200 and 400 MUg m( 1) of microcystins crude extract. The current study addresses the possible toxic effects of microcystins crude extract to O. niloticus. The results cleared that microcystins crude extract (containing MC-LR) is toxic to O. niloticus in time- and dose-dependent manners. PMID- 22095252 TI - Pulmonary artery banding for neonates and early infants with low body weight. AB - Open heart surgery for infants with low body weight (BW) remains still a challenge. Pulmonary artery banding (PAB) is a useful surgical palliation for small neonates and early infants with excessive pulmonary blood flow who are unable to withstand a heart surgery. This study retrospectively reviewed neonates and infants who underwent PAB to assess the surgical results and the validity of our PAB. We selected 38 acyanotic infants and neonates and divided them into 2 groups: low BW (< 2.5 kg, n = 15, group L) and normal or high BW (>= 2.5 kg, n = 23, group NH). The average BW at the time of PAB was 2.8 +/- 1.1 kg (range, 1.2-5.8 kg), and the average age at the time of PAB was 41.8 +/- 44.8 days (range, 2-151 days). Using a 3-mm-wide polyester tape, we tightened the main pulmonary artery to obtain the circumference of (19 mm + 1 mm for each kg of BW). There was no early death but one late death in each group. Postoperative BW continuously increased 1 month after PAB in both groups, although BW was significantly lower in group L than in group NH. Intracardiac repair (ICR) was accomplished in 31 patients (13 in group L and 18 in group NH) at average ages of 1.5 years, while the remaining 5 patients are awaiting ICR. In conclusion, PAB using our formula for the infants even weighing < 2.5 kg has low mortality and is effective as a bridge to ICR. PMID- 22095253 TI - Prenatal diagnosis of citrin deficiency in a Chinese family with a fatal proband. AB - Citrin deficiency (CD) is an autosomal recessive disorder with SLC25A13 as causative gene that encodes citrin, the liver-type aspartate/glutamate carrier isoform 2 (AGC2). Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), the major CD phenotype at pediatric age, has been previously reported as a self-limiting condition with clinical presentations resolving between 6 months and 1 year of life. We report the prenatal diagnosis of CD in a family with a fatal NICCD proband. The proband was a 10-month-old male presenting cough for 8 days and jaundiced skin 1 day. Physical examination revealed fever, dark jaundiced sclera and skin, hoarse breathing sounds, and hepatosplenomegaly. Laboratory tests uncovered elevated cholestatic indices, increased ammonia, and prolonged activated partial thromboplastin time and prothrombin time, and reduced fibrinogen. Sonography showed the features of liver cirrhosis. Metabolome analysis uncovered large quantity of 4-hydroxyphenyllactate and dicarboxylates in urine and increased citrulline and methionine in blood. The patient passed away due to liver failure at his age of 13.5 months. Mutation analysis revealed him a homozygote of 851del4, a four-base deletion in exon 9 of SLC25A13 gene. On request of the parents who had a second fetus, prenatal diagnosis of CD was performed by PCR-electrophoresis following amniocentesis and amniocyte culture, and demonstrated the fetus a carrier of the same mutation. The fatal proband in the present report has provided clinical evidence challenging the traditional concept on NICCD prognosis. Moreover, as the first trial on CD prenatal diagnosis, this study might open a novel area for clinical management of CD. PMID- 22095254 TI - Creutzfeldt-Jakob disease with paralysis of the unilateral vocal cord and soft palate. AB - Creutzfeldt-Jakob disease (CJD) is a progressive disease that is characterized by the accumulation of abnormal prion-like proteins in the central nervous system. The cerebral cortex is primarily affected in CJD, leading to spongiform changes and dementia. To date, there have been no reported cases of CJD, with local neuroparalysis discovered at an early stage of the disease. Here, we describe a patient who presented unilateral vocal cord and soft palate paralysis before the progression of CJD. After developing forgetfulness 6 months ago, a 76-year-old woman was presented at department of Otorhinolaryngology in a general hospital for recently developed hoarseness and dysphagia. In the oral and laryngeal endoscopic findings, unilateral paralysis of the vocal cord and soft palate was noted. On videofluorography, the larynx failed to elevate straight on swallowing. The right tongue pharyngeal wall was lax, and some contrast agent was retained in the lower right piriform sinus. The paralysis was thought to be due to the glossopharyngeal nerve or vagal nerve damage, which was caused by peripheral nerve injury or infranuclear palsy. Diffusion-weighted magnetic resonance imaging (MRI) revealed high signals in the cerebral cortical area (a signature feature of CJD). The patient died 2.5 years after the onset of illness. The patient was diagnosed as probable sporadic CJD. Since we could not detect any peripheral organic findings that could cause the paralysis, we suspect that CJD is responsible for the paralysis. In treating CJD patients with neurological signs, exclusive investigation is required to obtain a more detailed picture of the disease. PMID- 22095251 TI - Personalizing medicine with clinical pharmacogenetics. AB - Clinical genetic testing has grown substantially over the past 30 years as the causative mutations for Mendelian diseases have been identified, particularly aided in part by the recent advances in molecular-based technologies. Importantly, the adoption of new tests and testing strategies (e.g., diagnostic confirmation, prenatal testing, and population-based carrier screening) has often been met with caution and careful consideration before clinical implementation, which facilitates the appropriate use of new genetic tests. Although the field of pharmacogenetics was established in the 1950s, clinical testing for constitutional pharmacogenetic variants implicated in interindividual drug response variability has only recently become available to help clinicians guide pharmacotherapy, in part due to US Food and Drug Administration-mediated product insert revisions that include pharmacogenetic information for selected drugs. However, despite pharmacogenetic associations with adverse outcomes, physician uptake of clinical pharmacogenetic testing has been slow. Compared with testing for Mendelian diseases, pharmacogenetic testing for certain indications can have a lower positive predictive value, which is one reason for underutilization. A number of other barriers remain with implementing clinical pharmacogenetics, including clinical utility, professional education, and regulatory and reimbursement issues, among others. This review presents some of the current opportunities and challenges with implementing clinical pharmacogenetic testing. PMID- 22095255 TI - Oxaliplatin in the adjuvant treatment of colon cancer. PMID- 22095256 TI - Inhibitory guidance in visual search: the case of movement-form conjunctions. AB - We used a probe-dot procedure to examine the roles of excitatory attentional guidance and distractor suppression in search for movement-form conjunctions. Participants in Experiment 1 completed a conjunction (moving X amongst moving Os and static Xs) and two single-feature (moving X amongst moving Os, and static X amongst static Os) conditions. "Active" participants searched for the target, whereas "passive" participants viewed the displays without responding. Subsequently, both groups located (left or right) a probe dot appearing in either an occupied or an unoccupied location. In the conjunction condition, the active group located probes presented on static distractors more slowly than probes presented on moving distractors, reversing the direction of the difference found within the passive group. This disadvantage for probes on static items was much stronger in conjunction than in single-feature search. The same pattern of results was replicated in Experiment 2, which used a go/no-go procedure. Experiment 3 extended the go/no-go procedure to the case of search for a static target and revealed increased probe localisation times as a consequence of active search, primarily for probes on moving distractor items. The results demonstrated attentional guidance by inhibition of distractors in conjunction search. PMID- 22095257 TI - Impact of tongue reduction on overall speech intelligibility, articulation and oromyofunctional behavior in 4 children with Beckwith-Wiedemann syndrome. AB - OBJECTIVE: The purpose of this study was to determine the impact of partial glossectomy (using the keyhole technique) on speech intelligibility, articulation, resonance and oromyofunctional behavior. PATIENTS AND METHODS: A partial glossectomy was performed in 4 children with Beckwith- Wiedemann syndrome between the ages of 0.5 and 3.1 years. An ENT assessment, a phonetic inventory, a phonemic and phonological analysis and a consensus perceptual evaluation of speech intelligibility, resonance and oromyofunctional behavior were performed. RESULTS: It was not possible in this study to separate the effects of the surgery from the typical developmental progress of speech sound mastery. Improved speech intelligibility, a more complete phonetic inventory, an increase in phonological skills, normal resonance and increased motor-oriented oral behavior were found in the postsurgical condition. The presence of phonetic distortions, lip incompetence and interdental tongue position were still present in the postsurgical condition. CONCLUSION: Speech therapy should be focused on correct phonetic placement and a motor-oriented approach to increase lip competence, and on functional tongue exercises and tongue lifting during the production of alveolars. Detailed analyses in a larger number of subjects with and without Beckwith-Wiedemann syndrome may help further illustrate the long-term impact of partial glossectomy. PMID- 22095258 TI - Self-assembled 3D architectures of Bi2TiO4F2 as a new durable visible-light photocatalyst. AB - A new hierarchical visible-light-driven photocatalyst Bi(2)TiO(4)F(2) was synthesized by a solvothermal method for the first time. The photocatalyst was characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), N(2) adsorption desorption (BET), UV-vis diffuse reflectance spectroscopy (DRS). Such hierarchical Bi(2)TiO(4)F(2) microspheres assembled by nanosheets were fabricated via an Ostwald ripening process in the absence of soft templates (surfactants). The as-prepared samples' bimodal pore-size distributions in the mesoporous region consisted of smaller intra-aggregated pores with peak pore diameter of ca. 4.6 nm and larger inter-aggregated pores with peak pore diameter of ca. 17.0 nm. The band gap of the obtained Bi(2)TiO(4)F(2) was estimated to be about 2.71-3.06 eV for various solvothermal treatment time. Owing to the hierarchical structure with bimodal pores, low band gaps and high crystallinity, the Bi(2)TiO(4)F(2) microspheres exhibited high photocatalytic performance and durability for the degradation of rhodamine B (RhB) under visible light (> 420 nm). It was proved that the photo-generated holes and OH radicals played an essential role for the oxidation of RhB. PMID- 22095259 TI - Genetic diversity contributes to abnormalities in pain behaviors between young and old rats. AB - Aging has profound yet unpredictable effects on pain perception and incidence of anxiety disorders. However, the mechanisms underlying age-related pathologies are confounded by contradictory observations in rodent models. Therefore, the goal of our study was to test the hypothesis that genetic variability contributes to age related pain behaviors and susceptibility to anxiety. To address this hypothesis, we examined pain and anxiety-like behavior in young or old Brown Norway (BN), Fisher 344, and BN/F344 (F1), three rat strains used in studies to evaluate the effect of aging. Mechanosensitive thresholds were assessed using the Von Frey assay, and visceral pain sensitivity was measured via the visceromotor response to colorectal distension. Anxiety-like behavior and exploration was quantified in the elevated plus maze. In the BN strain, old rats exhibited increased mechanosensitive thresholds compared to young rats; however, age did not affect visceral sensitivity in this strain. In F344-BN rats, the number of abdominal contractions induced by the highest colonic distension pressure was significantly lower in old rats. However, following colonic sensitization, a difference was no longer apparent. In the F-344 strain, visceral hypersensitivity following afferent sensitization was evident in young rats at all distension pressures but was not observed in older animals at 20 mmHg. Aging significantly reduced maze exploration across all strains. Our data demonstrate that age- and strain-related alterations exist in pain behavior and highlight the effects of aging on exploratory behavior. These findings suggest that strain differences contribute to the controversial data on the effects of aging on pain perception. PMID- 22095260 TI - Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans. AB - Relationship between thymic function and elderly survival has been suspected, despite the fact that formal proof is elusive due to technical limitations of thymic function-related markers. The newly described sj/beta-TREC ratio allows now, by overcoming these limitations, an accurate measurement of thymic output in elderly humans. Thus, the aim of this study was to determine the impact of thymic function and inflammatory markers on healthy elderly human survival. Healthy volunteers (n = 151), aged over 65, were asked to participate (CARRERITAS cohort). Subjects were excluded if diagnosed of dementia or, during the last 6 months, had clinical data of infection, hospital admission, antitumor therapy, or any treatment that could influence the immune status. Thymic function (sj/beta TREC ratio), CD4:CD8 T cell ratio, C-reactive protein, interleukin-6, and neutrophilia were determined from basal samples. All basal variables and age were associated with 2-year all-cause mortality. Multivariate analysis showed that only thymic function and C-reactive protein were independently associated with time to death. In conclusion, we show, for the first time, the direct role of thymic function in human survival. C-reactive protein raise is also a marker of mortality in the healthy elderly, in a thymic-independent way. PMID- 22095261 TI - Fo shou san, an ancient herbal decoction prepared from angelicae sinensis radix and chuanxiong rhizoma, induces erythropoietin expression: a signaling mediated by the reduced degradation of hypoxia-inducible factor in cultured liver cells. AB - Fo Shou San (FSS) is an ancient herbal decoction composed of Angelicae Sinensis Radix (ASR; Danggui) and Chuanxiong Rhizoma (CR; Chuanxiong) in a ratio of 3:2. FSS is mainly prescribed for patients having a deficiency of blood supply, and it indeed has been shown to stimulate the production of erythropoietin (EPO) in cultured cells. In order to reveal the mechanism of this FSS-induced EPO gene expression, the upstream regulatory cascade, via hypoxia-induced signaling, was revealed here in cultured hepatocellular carcinoma cell line Hep3B. The induction of EPO gene expression, triggered by FSS, was revealed in cultured hepatocytes by: (i) the increase of EPO mRNA; and (ii) the activation of the hypoxia response element (HRE), an upstream regulator of the EPO gene. The FSS-induced EPO gene expression was triggered by an increased expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein; however, the mRNA expression of HIF-1 alpha was not altered by the treatment of FSS. The increased HIF-1 alpha was a result of reduced protein degradation after the FSS treatment. The current results therefore provide one of the molecular mechanisms of this ancient herbal decoction for its hematopoietic function. PMID- 22095262 TI - Antimalarial efficacy of a quantified extract of Nauclea pobeguinii stem bark in human adult volunteers with diagnosed uncomplicated falciparum malaria. Part 1: a clinical phase IIA trial. AB - The aim of this phase IIA clinical trial was to assess the efficacy of an 80 % ethanolic quantified extract (containing 5.6 % strictosamide as the putative active constituent) from Nauclea pobeguinii stem bark denoted as PR 259 CT1 in a small group of adult patients diagnosed with uncomplicated falciparum malaria. Results obtained from a phase I clinical trial on healthy male volunteers indicated that the oral administration during meals of two 500 mg capsules three times daily (each eight hours) during seven days was well tolerated and showed only mild and self-resolving adverse effects. This PR 259 CT1 drug regimen was obtained by mathematical conversion of animal doses obtained in several in vivo studies in mice to human equivalent doses as in falciparum malaria patients. The phase IIA study was an open cohort study in eleven appraisable adult patients suffering from proven Plasmodium falciparum malaria. The study was specifically designed to assess the efficacy of PR 259 CT1 administered with a dose regimen of two 500 mg capsules three times daily for three days, followed by outpatient treatment of one 500 mg capsule three times daily for the next four days, in order to prove that this therapeutic dose, which was calculated from animal doses, was effective to treat adult malaria patients and consequently useful for a future Phase IIB clinical trial. This study would then substitute a dose escalating trial, which in general is used to find the appropriate dose for clinical studies. The phase IIA clinical trial was carried out according to the WHO 2003 14-day test, and the results revealed that all eleven patients were completely cleared of parasitemia and fever on days 3, 7, and 14 except for one patient, who experienced a recurrence of parasitemia at days 7 until 14. Besides this adequate clinical and parasitological response (ACPR), this trial also demonstrated that PR 259 CT1 was well tolerated with only mild and self-resolving adverse effects including fatigue and headache, which were in accordance with those found in the phase I clinical trial. Moreover, all symptoms progressively disappeared, and no symptoms were observed on day 14. Although the number of patients included in this study was rather limited, the statistical analysis nevertheless suggested the efficacy and tolerability of PR 259 CT1, which indicated that this herbal medicinal product might be considered as a putative candidate for a large scale clinical trial. PMID- 22095263 TI - A sensitive method for determination of platycodin d in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study. AB - Platycodin D (PD), a major component isolated from the root of Platycodon grandiflorum, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated to determine the PD in rat plasma. This method was further applied to assess the pharmacokinetics of PD in rats following administration of a single dose. Liquid chromatography tandem mass spectrometry (LC/MS/MS) in multiple reaction monitoring mode (MRM) was used in the method, and tubeimoside I was used as the internal standard (IS). A simple protein precipitation based on methanol (MeOH) was employed. The combination of a simple sample cleanup and short chromatographic running time (4 min) increased the throughput of the method substantially. The method was validated over the range of 0.5-1000 ng/mL with a correlation coefficient > 0.99. The lower limit of quantification was 0.5 ng/mL for PD in plasma. Intra- and inter-day accuracies for PD were 90-115 % and 96-108 %, respectively, and the inter-day precision was less than 15 %. After a single oral dose of 10 mg/kg of PD, its mean peak plasma concentration ( CMAX) was 13.7 +/- 4.5 ng/mL at 0.5 h. The area under the plasma concentration-time curve ( AUC0-24 H) was 35.4 +/- 16.1 h.ng/mL, and the elimination half-life ( T1/2) was 1.48 +/- 0.13 h. In case of intravenous administration of PD at a dosage of 0.5 mg/kg, the area under the plasma concentration-time curve ( AUC0-24 H) was 2203 +/- 258 h . ng/mL, and the elimination half-life (T1/2) was 6.57 +/- 0.70 h. Based on the results, the oral bioavailability of PD in rats at 10 mg/kg is 0.079 %. PMID- 22095265 TI - Recognizing syphilis in an HIV-infected patient. PMID- 22095266 TI - Minimizing tracheobronchial aspiration in the tube-fed patient part 1. PMID- 22095267 TI - Hyper-IgE syndrome: diagnosis of a 3-year-old with 10-year follow-up. PMID- 22095268 TI - Do ankle injuries always require an X-ray? PMID- 22095272 TI - Primary care management of food allergy and food intolerance. AB - The incidence of food allergies is steadily increasing. Due to potentially life threatening complications, it is important that primary care providers recognize and appropriately manage these disorders. This article includes a discussion of the current evidence-based guidelines for the diagnosis, screening, and management of food allergies. PMID- 22095273 TI - A close up view of pneumococcal disease. AB - Pneumococcal disease remains a threat despite an available vaccine. Primary care nurse practitioners must be prepared to prevent as well as treat pneumococcal infections. PMID- 22095274 TI - Safe prescribing for the elderly. AB - Prescribing for older adults is a complex and high-risk process. Age-related changes produce differences in the way lderly patients respond to and process medication. This article discusses age-related changes, common problems that increase risk for older adults, strategies for improving adherence, and models for safe and effective prescribing. PMID- 22095277 TI - Mutant p53 protein, master regulator of human malignancies: a report on the Fifth Mutant p53 Workshop. PMID- 22095276 TI - Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms. AB - The glial environment is an important determinant of neuronal health in experimental models of neurodegeneration. Specifically, astrocytes have been shown, dependent on context, to be both injurious and protective. Human pluripotent stem cells offer a powerful new system to improve our understanding of the mechanisms underlying astrocyte-mediated neuroprotection. Here, we describe a human embryonic stem cell (HESC)-based system to assess the scope and mechanism of human astrocyte-mediated neuroprotection. We first report the generation of enriched and functional HESC-derived astrocytes, by combining BMP mediated Smad and LIF-mediated JAK-STAT signalling. These astrocytes promote the protection of HESC-derived neurons against oxidative insults. Moreover, their neuroprotective capacity can be greatly enhanced by treatment with the nuclear factor-erythroid 2-related factor 2 (Nrf2)-activating triterpenoid 1[2-Cyano-3,12 dioxool-eana-1,9(11)-dien-28-oyl] trifluoroethylamide (CDDO(TFEA)). Activation of the transcription factor Nrf2 in human astrocytes by CDDO(TFEA) treatment induced expression of the glutamate-cysteine ligase (GCL) catalytic subunit, leading to enhanced GCL activity and glutathione production, and strong neuroprotection against H(2)O(2). This enhanced neuroprotection was found to be dependent on astrocytic GCL activity, unlike the basal neuroprotection afforded by untreated astrocytes. Direct treatment of HESC-derived neurons with CDDO(TFEA) elicited no induction of Nrf2 target genes, nor any neuroprotection. Thus, human astrocytes can mediate neuroprotection through glutathione-dependent and glutathione independent mechanisms, and represent a therapeutic target for human disorders associated with neuronal oxidative stress. PMID- 22095278 TI - RP58/ZNF238 directly modulates proneurogenic gene levels and is required for neuronal differentiation and brain expansion. AB - Although neurogenic pathways have been described in the developing neocortex, less is known about mechanisms ensuring correct neuronal differentiation thus also preventing tumor growth. We have shown that RP58 (aka zfp238 or znf238) is highly expressed in differentiating neurons, that its expression is lost or diminished in brain tumors, and that its reintroduction blocks their proliferation. Mice with loss of RP58 die at birth with neocortical defects. Using a novel conditional RP58 allele here we show that its CNS-specific loss yields a novel postnatal phenotype: microencephaly, agenesis of the corpus callosum and cerebellar hypoplasia that resembles the chr1qter deletion microcephaly syndrome in human. RP58 mutant brains maintain precursor pools but have reduced neuronal and increased glial differentiation. Well-timed downregulation of pax6, ngn2 and neuroD1 depends on RP58 mediated transcriptional repression, ngn2 and neuroD1 being direct targets. Thus, RP58 may act to favor neuronal differentiation and brain growth by coherently repressing multiple proneurogenic genes in a timely manner. PMID- 22095279 TI - ICDS 2011 meeting 'Signaling in cell death survival, proliferation and degeneration'. PMID- 22095280 TI - In mouse embryonic fibroblasts, neither caspase-8 nor cellular FLICE-inhibitory protein (FLIP) is necessary for TNF to activate NF-kappaB, but caspase-8 is required for TNF to cause cell death, and induction of FLIP by NF-kappaB is required to prevent it. AB - Binding of TNF to TNF receptor-1 can give a pro-survival signal through activation of p65/RelA NF-kappaB, but also signals cell death. To determine the roles of FLICE-inhibitory protein (FLIP) and caspase-8 in TNF-induced activation of NF-kappaB and apoptosis, we used mouse embryonic fibroblasts derived from FLIP and caspase-8 gene-deleted mice, and treated them with TNF and a smac-mimetic compound that causes degradation of cellular inhibitor of apoptosis proteins (cIAPs). In cells treated with smac mimetic, TNF and Fas Ligand caused wild-type and FLIP(-/-) MEFs to die, whereas caspase-8(-/-) MEFs survived, indicating that caspase-8 is necessary for death of MEFs triggered by these ligands when IAPs are degraded. By contrast, neither caspase-8 nor FLIP was required for TNF to activate p65/RelA NF-kappaB, because IkappaB was degraded, p65 translocated to the nucleus, and an NF-kappaB reporter gene activated normally in caspase-8(-/-) or FLIP(-/-) MEFs. Reconstitution of FLIP(-/-) MEFs with the FLIP isoforms FLIP L, FLIP-R, or FLIP-p43 protected these cells from dying when treated with TNF or FasL, whether or not cIAPs were depleted. These results show that in MEFs, caspase-8 is necessary for TNF- and FasL-induced death, and FLIP is needed to prevent it, but neither caspase-8 nor FLIP is required for TNF to activate NF kappaB. PMID- 22095281 TI - IAPs: guardians of RIPK1. AB - Deregulation of innate immune signalling and cell death form the basis of most human disease pathogenesis. Inhibitor of APoptosis (IAP) protein-family members are frequently overexpressed in cancer and contribute to tumour cell survival, chemo-resistance, disease progression and poor prognosis. Although best known for their ability to regulate caspases, IAPs also influence ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. Recent advances in our understanding of the molecular mechanisms through which IAPs influence cell death and innate immune responses have provided new insights into novel strategies for treatment of cancer. In this review we discuss our current understanding of IAP-mediated NF-kappaB signalling, as well as elaborate on unexpected insights into the involvement of IAPs in regulating the 'Ripoptosome', a novel intrinsic cell death-inducing platform. We propose an evolutionarily conserved concept whereby IAPs function as guardians of killer platforms such as the apoptosome in Drosophila and the Ripoptosome in mammals. PMID- 22095282 TI - Arginine methylation-dependent regulation of ASK1 signaling by PRMT1. AB - Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is implicated in modulation of cellular processes including gene transcription. The role of PRMTs in the regulation of intracellular signaling pathways has remained obscure, however. We now show that PRMT1 methylates apoptosis signal-regulating kinase 1 (ASK1) at arginine residues 78 and 80 and thereby negatively regulates ASK1 signaling. PRMT1-mediated ASK1 methylation attenuated the H(2)O(2)-induced stimulation of ASK1, with this inhibitory effect of PRMT1 being abolished by replacement of arginines 78 and 80 of ASK1 with lysine. Furthermore, depletion of PRMT1 expression by RNA interference potentiated H(2)O(2)-induced stimulation of ASK1. PRMT1-mediated ASK1 methylation promoted the interaction between ASK1 and its negative regulator thioredoxin, whereas it abrogated the association of ASK1 with its positive regulator TRAF2. Moreover, PRMT1 depletion potentiated paclitaxel-induced ASK1 activation and apoptosis in human breast cancer cells. Together, our results indicate that arginine methylation of ASK1 by PRMT1 contributes to the regulation of stress induced signaling that controls a variety of cellular events including apoptosis. PMID- 22095283 TI - Granzymes, cytotoxic granules and cell death: the early work of Dr. Jurg Tschopp. AB - Within the powerful legacy left by Jurg Tschopp, we should not forget his early work that helped to elucidate the molecular pathways responsible for the clearance of virus-infected and transformed cells by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Jurg's skilful biochemical approach formed a firm platform upon which the work of so many other biochemists, cell biologists and immunologists would come to rely. Jurg coined the shorthand term 'granzyme' to denote the individual members of a family of serine proteases sequestered in and secreted from the cytotoxic granules of CTL/NK cells. He was also one of the first to describe the lytic properties of purified perforin and to postulate the synergy of perforin and granzymes, which we now know to underpin target cell apoptosis. Jurg was a major protagonist in the debate that raged throughout the 1980's and early 1990's on the physiological relevance of the 'granule exocytosis' pathway. Ultimately, resolving this issue led Jurg and his colleagues to even greater and impactful discoveries in the broader field of apoptosis research. Jurg Tschopp ranks with other pioneers, particularly Gideon Berke, Chris Bleackley, Pierre Golstein, Pierre Henkart and Eckhard Podack for making seminal discoveries on our understanding of how the immune system eliminates dangerous cells. PMID- 22095284 TI - Overlapping functions of microRNAs in control of apoptosis during Drosophila embryogenesis. AB - Regulation of apoptosis is crucial for tissue homeostasis under normal development and environmental stress. In Drosophila, cell death occurs in different developmental processes including embryogenesis. Here, we report that two members of the miR-2 seed family of microRNAs, miR-6 and miR-11, function together to limit the level of apoptosis during Drosophila embryonic development. Mutants lacking both miR-6 and miR-11 show embryonic lethality and defects in the central nervous system (CNS). We provide evidence that miR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective (hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. These findings demonstrate that the activity of the proapoptotic genes is kept in check by miR-6/11 to ensure normal development. PMID- 22095285 TI - Mutation of ATF4 mediates resistance of neuronal cell lines against oxidative stress by inducing xCT expression. AB - Selecting neuronal cell lines for resistance against oxidative stress might recapitulate some adaptive processes in neurodegenerative diseases where oxidative stress is involved like Parkinson's disease. We recently reported that in hippocampal HT22 cells selected for resistance against oxidative glutamate toxicity, the cystine/glutamate antiporter system x(c)(-), which imports cystine for synthesis of the antioxidant glutathione, and its specific subunit, xCT, are upregulated. (Lewerenz et al., J Neurochem 98(3):916-25). Here, we show that in these glutamate-resistant HT22 cells upregulation of xCT mediates glutamate resistance, and xCT expression is induced by upregulation of the transcription factor ATF4. The mechanism of ATF4 upregulation consists of a 13 bp deletion in the upstream open reading frame (uORF2) overlapping the ATF4 open reading frame. The resulting uORF2-ATF4 fusion protein is efficiently translated even at a low phosphorylation levels of the translation initiation factor eIF2alpha, a condition under which ATF4 translation is normally suppressed. A similar ATF4 mutation associated with prominent upregulation of xCT expression was identified in PC12 cells selected for resistance against amyloid beta-peptide. Our data indicate that ATF4 has a central role in regulating xCT expression and resistance against oxidative stress. ATF4 mutations might have broader significance as upregulation of xCT is found in tumor cells and associated with anticancer drug resistance. PMID- 22095286 TI - The PIDDosome, DNA-damage-induced apoptosis and beyond. AB - P53-induced protein with a death domain (PIDD) was cloned as a death domain (DD) containing protein whose expression is induced by p53. It was later described as the core of a molecular platform-activating caspase-2, named the PIDDosome. These first results pointed towards a role for PIDD in apoptosis, in response to DNA damage. Identification of new PIDDosome complexes involved in DNA repair and nuclear factor-kappaB signaling challenged this early concept. PIDD functions are growing as new complexes and new interaction partners are being discovered, and as additional functions are being revealed. A fascinating feature of PIDD lies within its complex and tight regulation mechanisms, which allow the molecule to fine-tune its different functions: from transcriptional regulation to the expression of different isoforms, and from the interaction with regulatory proteins to an ingenious post-translational cleavage mechanism generating various active fragments with specific functions. Further studies still need to be carried out to provide answers to many unresolved issues and to reconcile conflicting results. This review aims at providing an overview of the current PIDD knowledge status. PMID- 22095287 TI - Necdin enhances muscle reconstitution of dystrophic muscle by vessel-associated progenitors, by promoting cell survival and myogenic differentiation. AB - Improving stem cell therapy is a major goal for the treatment of muscle diseases, where physiological muscle regeneration is progressively exhausted. Vessel associated stem cells, such as mesoangioblasts (MABs), appear to be the most promising cell type for the cell therapy for muscular dystrophies and have been shown to significantly contribute to restoration of muscle structure and function in different muscular dystrophy models. Here, we report that melanoma antigen encoding gene (MAGE) protein necdin enhances muscle differentiation and regeneration by MABs. When necdin is constitutively overexpressed, it accelerates their differentiation and fusion in vitro and it increases their efficacy in reconstituting regenerating myofibres in the alpha-sarcoglycan dystrophic mouse. Moreover, necdin enhances survival when MABs are exposed to cytotoxic stimuli that mimic the inflammatory dystrophic environment. Taken together, these data demonstrate that overexpression of necdin may be a crucial tool to boost therapeutic applications of MABs in dystrophic muscle. PMID- 22095288 TI - PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk. AB - Autophagy, a process in which cellular components are engulfed and degraded within double-membrane vesicles termed autophagosomes, has an important role in the response to oxidative damage. Here we identify a novel cascade of phosphorylation events, involving a network of protein and lipid kinases, as crucial components of the signaling pathways that regulate the induction of autophagy under oxidative stress. Our findings show that both the tumor suppressor death-associated protein kinase (DAPk) and protein kinase D (PKD), which we previously showed to be phosphorylated and consequently activated by DAPk, mediate the induction of autophagy in response to oxidative damage. Furthermore, we map the position of PKD within the autophagic network to Vps34, a lipid kinase whose function is indispensable for autophagy, and demonstrate that PKD is found in the same molecular complex with Vps34. PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate (PI(3)P) formation, and autophagosome formation. Consistent with its identification as a novel inducer of the autophagic machinery, we show that PKD is recruited to LC3 positive autophagosomes, where it localizes specifically to the autophagosomal membranes. Taken together, our results describe PKD as a novel Vps34 kinase that functions as an effecter of autophagy under oxidative stress. PMID- 22095289 TI - Sensitization of ovarian carcinoma cells with zoledronate restores the cytotoxic capacity of Vgamma9Vdelta2 T cells impaired by the prostaglandin E2 immunosuppressive factor: implications for immunotherapy. AB - Epithelial ovarian cancer (EOC) usually spreads into the peritoneal cavity, thereby providing an opportunity for intraperitoneal adoptive immunotherapy with Vgamma9Vdelta2 T lymphocytes, a T cell subpopulation endowed with high lytic properties against tumor cells. However, previous studies have reported that Vgamma9Vdelta2 T cells fail to expand from peripheral blood mononuclear cells in one-third of patients with cancer. Here, from a cohort of 37 patients with EOC, a multiple correspondence analysis identified three populations, one of which was not suitable for Vgamma9Vdelta2 T-cell adoptive therapy. Interestingly, the ineligible patients were identified based on the frequency of Vgamma9Vdelta2 T cells in their peripheral blood and the patients' age. The average time to tumor recurrence was also found to be significantly different between the three populations, suggesting that the innate immune response is involved in EOC prognosis. A dramatic decrease in the lytic properties of Vgamma9Vdelta2 T cells occurred following incubation with ascitic supernatant and was found to be associated with reduced perforin/granzyme degranulation. Prostaglandin E2, but not IL-6, IL-10, VEGF or TGF-beta, showed immunosuppressive effects in Vgamma9Vdelta2 T cells. Interestingly, our results emphasize that pretreating ovarian tumor cells with zoledronate partially reverses the immunosuppressive effects of ovarian cancer-associated ascites and restores a high level of lytic activity. These data sustain that optimal Vgamma9Vdelta2 T-cell adoptive immunotherapy previously requires counteracting the tumor immunosuppressive microenvironment. Altogether, our findings provide a rationale for clinically evaluating Vgamma9Vdelta2 T-cell adoptive immunotherapy with intraperitoneal carcinomatosis presensitization by zoledronate in patients with EOC. PMID- 22095290 TI - Fatty lesions in intra-articular loose bodies: a histopathological study of non primary synovial chondromatosis cases. AB - Intra-articular loose bodies (ILBs) are not uncommon conditions in patients with various joint diseases. Their morphological alterations have been investigated in detail, but little attention has been paid to their fatty lesions. In this study, we examined fatty bone marrow, fat cells without bone marrow structures (extramedullary fat cells), and their necrotic changes in 55 ILBs surgically removed from 42 patients, excluding primary synovial chondromatosis cases. The presence of viable re-vascularized vessels with or without enchondral ossification could discriminate 19 re-attached ILBs from 36 true free ILBs. Fatty bone marrow was found in 25 ILBs, and its necrosis was recognized in 11 (44.0%) of them. Extramedullary fat cells, characterized by single or clustered fat cells focally or multifocally distributed in fibrous or cartilaginous stroma, were identified in seven true free ILBs (7of 55, 12.7%), and all of them were focally necrotic. Unique lipomembranous changes were detected in 7 (12.7%) of 55 ILBs; they were found in 4 (36.4%) of 11 ILBs of necrotic bone marrow and were associated with 3 (42.9%) of 7 necrotic extramedullary fatty lesions. These changes were highlighted by periodic-acid Schiff and Masson's trichrome stain more clearly. We concluded that extramedullary fat cells represent lipometaplasia in ILBs with no blood supply. We considered that lipomembranous changes in ILBs can be a useful hallmark for necrotic bone marrow or necrosis of extramedullary lipometaplastic lesions. PMID- 22095291 TI - Buffalo (Bubalus bubalis) epiphyseal proteins counteract arsenic-induced oxidative stress in brain, heart, and liver of female rats. AB - Arsenic (As) toxicity through induction of oxidative stress is a well-known mechanism of organ toxicity. To address this problem, buffalo epiphyseal proteins (BEP, at 100 MUg/kg BW, i.p. for 28 days) were administered intraperitoneally to female Wistar rats exposed to As (100 ppm sodium arsenite via drinking water for 28 days). Arsenic exposure resulted in marked elevation in lipid peroxidation in brain, cardiac, and hepatic tissues, whereas significant (p < 0.05) adverse change in catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, and reduced glutathione level were observed in cardiac, hepatic, and brain tissues of As-administered animals. BEP significantly (p < 0.05) counteracted all the adverse changes in antioxidant defense system brought about by As administration. Based on these results, we consider BEP as a potent antioxidant to be used for protection from arsenic-induced oxidative stress related damage of vital organs. PMID- 22095292 TI - Protective effect of cerium ion against ultraviolet B radiation-induced water stress in soybean seedlings. AB - Effects of cerium ion (Ce(III)) on water relations of soybean seedlings (Glycine max L.) under ultraviolet B radiation (UV-B, 280-320 nm) stress were investigated under laboratory conditions. UV-B radiation not only affected the contents of two osmolytes (proline, soluble sugar) in soybean seedlings, but also inhibited the transpiration in soybean seedlings by decreasing the stomatal density and conductance. The two effects caused the inhibition in the osmotic and metabolic absorption of water, which decreased the water content and the free water/bound water ratio. Obviously, UV-B radiation led to water stress, causing the decrease in the photosynthesis in soybean seedlings. The pretreatment with 20 mg L(-1) Ce(III) could alleviate UV-B-induced water stress by regulating the osmotic and metabolic absorption of water in soybean seedlings. The alleviated effect caused the increase in the photosynthesis and the growth of soybean seedlings. It is one of the protective effect mechanisms of Ce(III) against the UV-B radiation-induced damage to plants. PMID- 22095293 TI - A delay equation model for oviposition habitat selection by mosquitoes. AB - We propose a patch type model for mosquitoes that have aquatic larvae inhabiting ponds. Partial differential equations (PDEs) model the larvae on each of several disconnected patches representing the ponds, with conditions varying in each patch, coupled via the adults in the air. From the PDEs a scalar delay differential equation, with multiple delays, for the total adult mosquito population is derived. The various delays represent the larval development times in the patches. The coefficients contain all the relevant information about the sizes and geometry of the individual patches inhabited by the larvae, the boundary conditions applicable to those patches and the diffusivity of the larvae in each patch. For patches of general shapes and sizes, and without the need to specify the criteria by which an adult mosquito selects an oviposition patch, the modern theory of monotone dynamical systems and persistence theory enables a complete determination of the conditions for the mosquito population to go extinct or to persist. More detailed biological insights are obtained for the case when the patches are squares of various sizes, which allows a detailed discussion of the effects of scale, and for two particular criteria by which mosquitoes might select patches for oviposition, being (i) selection based solely on patch area, and (ii) selection based both on area and expected larval survival probability for each patch. In some parameter regimes, counterintuitive phenomena are predicted. PMID- 22095294 TI - Comparison of averaging techniques for the calculation of the 'European average exposure indicator' for particulate matter. AB - A comparison of various averaging techniques to calculate the Average Exposure Indicator (AEI) specified in European Directive 2008/50/EC for particulate matter in ambient air has been performed. This was done for data from seventeen sites around the UK for which PM(10) mass concentration data is available for the years 1998-2000 and 2008-2010 inclusive. The results have shown that use of the geometric mean produces significantly lower AEI values within the required three year averaging periods and slightly lower changes in the AEI value between the three year averaging periods than the use of the arithmetic mean. The use of weighted means in the calculation, using the data capture at each site as the weighting parameter, has also been tested and this is proposed as a useful way of taking account of the confidence of each data set. PMID- 22095295 TI - Controlled delivery of basal level of insulin from chitosan-zinc-insulin-complex loaded thermosensitive copolymer. AB - Present study was aimed at developing a delivery system for controlled release of insulin, based on chitosan-zinc-insulin complex incorporated into poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (4500 Da) thermosensitive polymer. In vitro release of insulin from the delivery system was studied in phosphate buffered saline (pH 7.4). The effect of zinc and chitosan on the stability of insulin in the delivery systems during release and storage at 4 degrees C and 37 degrees C was investigated. Circular dichroism, calorimetry, polyacrylamide gel electrophoresis (PAGE), high-performance liquid chromatography, and matrix assisted laser desorption/ionization-time-of-flight mass spectrometry were used to determine the stability of insulin released and extracted from the gel. A significant decrease (p < 0.05) in the initial burst was observed from the formulation containing chitosan-zinc-insulin complex, compared with all other formulations. The formulations containing chitosan-zinc-insulin complex showed a long-term controlled release (~ 84 days) of insulin. Insulin released and extracted from the gel was conformationally and structurally stable. Bands at 12 kDa were observed in native PAGE, but sodium dodecyl sulfate-PAGE indicated noncovalent nature of insulin aggregates. Thus, the chitosan-zinc-insulin complex significantly reduced the initial burst release and prolonged the release of insulin. It also improved the stability of insulin in the delivery system and protected insulin from aggregation during the entire release period and storage. PMID- 22095296 TI - Low levels of X-inactive specific transcript in somatic cell nuclear transfer embryos derived from female bovine freemartin donor cells. AB - The present study compared developmental potential, telomerase activity and transcript levels of X-linked genes (HPRT, MECP2, RPS4X, SLC25A6, XIAP, XIST and ZFX) in bovine somatic cell nuclear transfer (SCNT) embryos reconstructed with cells derived from a freemartin (female with a male co-twin) or from normal female cattle (control). The rates of cleavage, development to blastocyst and hatched blastocyst stage, and the mean numbers of total and inner cell mass cells in the freemartin SCNT embryos were not significantly different from those of control SCNT embryos (p > 0.05). The levels of telomerase activity analyzed by RQ TRAP in the freemartin SCNT embryos were also similar to those of the normal SCNT embryos. Transcript levels of HPRT, MECP2, RPS4X and XIAP, measured by quantitative real-time RT-PCR, were not significantly different between the control and freemartin SCNT embryos (p > 0.05). However, the transcript levels of SLC25A6, XIST and ZFX were significantly decreased in the freemartin SCNT embryos compared to control SCNT embryos (p < 0.05). Transfer of 71 freemartin SCNT embryos to 22 recipient cows resulted in 4 (18%) pregnancies, which were lost between days 28 and 90 of gestation. Taken together, the present study demonstrates that the transcript levels of several X-linked genes, especially XIST, showed an aberrant pattern in the freemartin SCNT embryos, suggesting aberrant X inactivation in freemartin clones which may affect embryo survival. PMID- 22095298 TI - The 4th Colorectal Meeting in Tianjin, China. PMID- 22095297 TI - Age-related cardiovascular disease and the beneficial effects of calorie restriction. AB - Aging is a well-recognized risk factor in the development of cardiovascular disease, which is the primary cause of death and disability in the elderly population. The normal process of aging is associated with progressive deterioration in structure and function of the heart and vasculature. These age related changes likely act as both a catalyst and accelerator in the development of cardiovascular disease. Since the aging population is one of the fastest growing segments of the population, it is of vital importance that we have a thorough understanding of the physiological changes that occur with aging that contribute to the high incidence of cardiovascular disease in this population. This insight will allow for the development of more targeted therapies that can prevent and treat these conditions. One such anti-aging strategy that has received considerable attention as of late is calorie restriction. Calorie restriction has emerged as one of the most effective and reproducible interventions for extending lifespan, as well as protecting against obesity, metabolic disorders, and cardiovascular disease. Herein, we review the multiple beneficial effects that calorie restriction and resveratrol exert on the cardiovascular system with a particular focus on aging. Although calorie restriction and resveratrol have proven to be very effective in preventing and treating the development of cardiovascular disease in animal models, studies continue as to whether these profound beneficial effects can translate to humans to improve cardiovascular health. PMID- 22095299 TI - D. Geisler and T. Garrett: Single incision laparoscopic colorectal surgery: a single surgeon experience of 102 consecutive cases. PMID- 22095300 TI - Resection of recurrent rectal cancer with encasement of external iliac vessels. PMID- 22095306 TI - High negative valence does not protect emotional event-related potentials from spatial inattention and perceptual load. AB - Previous research suggests that intense, emotional pictures at fixation elicit an early posterior negativity (EPN) and a late positive potential (LPP) despite manipulations of spatial inattention and perceptual load. However, if high emotional intensity protects against such manipulations, then these manipulations should reduce emotional effects on EPN and LPP more strongly for medium than for intense emotional pictures. To test this prediction, pictures that were high negative, medium negative, or neutral were shown at fixation, and a small letter string was superimposed on the picture center. When participants attended the pictures, there were clear emotional effects on EPN and LPP. When participants attended the letter string, the emotional effects on LPP decreased; this decrease was smaller for medium than for high negative pictures. Thus, opposite of predictions, spatial inattention reduced the emotional effects more strongly for high than for medium negative pictures. As a manipulation of perceptual load, participants performed the letter task with one, three, or six relevant letters. Irrespective of load, EPN and LPP were similar for high and medium negative pictures. Our findings suggest that high negative valence does not protect EPN and LPP more strongly from effects of spatial inattention and perceptual load than does medium negative valence. PMID- 22095307 TI - High prevalence detection of Chlamydia trachomatis by polymerase chain reaction in endocervical samples of infertile women attending university hospital in Manaus-Amazonas, Brazil. AB - BACKGROUND: We established for the first time the prevalence of Chlamydia trachomatis infection among infertile women in Manaus Amazonas Brazil using the polymerase chain reaction (PCR) technique. METHODS: 106 women were studied at a public university hospital fertility clinic for infertility problems correlated with chlamydia infection. Social-economic and clinical information was obtained before medical examination to obtain samples for the amplification of C. trachomatis DNA plasmid. RESULTS: The prevalence of chlamydial infection among infertile women was 52.8, and 51.8% of the positive participants were older than 30 years of age (p = 0.8697). Of the 56 women positive for C. trachomatis, 31 (55.4%) had never given birth, while 9 (16%) had a pregnancy resulting in fetal death. Our findings also revealed that these patients had a low socio-economic status and high unemployment (p = 0.0274), and a significant association of 5% (p < 0.05) of chlamydial infection with family income. CONCLUSIONS: Due to the high prevalence of C. trachomatis, concerns about effects on reproductive health and fertility are undertaken. Therefore, we believe it is extremely necessary to implement large-scale PCR-based screening as part of routine clinical detection programs concerning preventive effects of chlamydial infection among this population. PMID- 22095308 TI - Pilot study: a randomised, double blind, placebo controlled trial of pancrealipase for the treatment of postprandial irritable bowel syndrome diarrhoea. AB - OBJECTIVE: To evaluate the efficacy of pancrealipase (PEZ) compared with placebo in the reduction of postprandial irritable bowel syndrome-diarrhoea (IBS-D). DESIGN: An intention to treat, double blind, randomised, crossover trial comparing PEZ to placebo for reduction of postprandial IBS-D. Patients had to recognise at least two different triggering foods, be willing to consume six baseline 'trigger meals' and again blinded with PEZ and placebo. Patients then chose which drug they preferred for another 25 meals. SETTING: Outpatient internal medicine practice clinic. PATIENTS: 255 patients were screened; 83 met the criteria, including 5 years of symptoms, recognised 'food triggers', no other identifiable cause for the symptoms, either a normal colonoscopy or barium enema while symptomatic and able to discontinue all anticholinergic medications. 69 patients were enrolled, 20 withdrew before randomisation, leaving 49 patients: 14 men, 35 women, mean age 52 years (SD 15.3). Over 60% had experienced symptoms for 11-30 years and 16% for more than 40 years. INTERVENTIONS: After completing six baseline meals, patients were randomised in blocks of four to receive either identical PEZ or a placebo for another six meals, and after a washout period of time received the alternative drug. MAIN OUTCOME MEASURES: The primary analysis was number of patients who chose PEZ over placebo for the extended use. RESULTS: Overall, 30/49 (61%) would have chosen PEZ (p=0.078), with first drug preference for PEZ at 0.002. Among the PEZ subgroup, PEZ use compared with placebo, demonstrated improvement in all symptoms (p<=0.001) for cramping, bloating, borborygami, urge to defecate, global pain and decrease stooling with increase in stool firmness. CONCLUSIONS: PEZ was found in a small group of patients to reduce postprandial IBS-D symptoms and deserves further evaluation. PMID- 22095309 TI - Endoscopic sinus surgery checklist. AB - Over 250,000 endoscopic sinus surgeries are performed yearly in the United States alone. Although overall complication rates are low, errors can lead to significant morbidity due to the close proximity of the sinuses to the orbit and skull base and the resultant potential for blindness, cerebrospinal fluid leak, and catastrophic bleeding. Surgical checklists are endorsed by the World Health Organization and have been incorporated into most U.S. operating rooms as a measure to minimize avoidable errors. Standardized surgical checklists were developed with general and/or orthopedic procedures in mind, but in many instances they fail to incorporate concerns specific to endoscopic sinus surgery (ESS). In response to this clinical problem, we sought to develop and institute an ESS surgical checklist. This checklist can serve as a template for physicians who perform ESS and wish to prevent avoidable adverse events. PMID- 22095310 TI - Synthesis of the complete series of mono acetates of N-acetyl-D-neuraminic acid. AB - The short syntheses of each of the mono-acetates of N-acetyl-D-neuraminic acid are reported. These are important molecules for studying the mechanism and function of enzymes which utilise Neu5Ac as a substrate. However, until now these molecules were not available as pure compounds and instead had to be studied as mixtures. Neu4,5Ac(2) and Neu5,8Ac(2) were synthesised from a common precursor in 2 and 4 steps respectively, while Neu2,4Ac(2) and Neu5,7Ac(2) were synthesised in 3 and 4 steps respectively from another common precursor. Both precursors could be easily prepared in 3 steps from Neu5Ac itself. Importantly, no scrambling of the anomeric stereochemistry was detected throughout the course of these syntheses. PMID- 22095311 TI - Convenient photooxidation of alcohols using dye sensitised zinc oxide in combination with silver nitrate and TEMPO. AB - A novel photooxidative system using dye sensitised zinc oxide in combination with silver nitrate and 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) in an aqueous solution is described. Under visible light irradiation the selective oxidation of alcohols to their corresponding aldehydes and ketones was effected in good to excellent yields. PMID- 22095312 TI - Sleep-disordered breathing is a risk factor for community-acquired alveolar pneumonia in early childhood. AB - BACKGROUND: Data are scarce with regard to risk factors for acute community acquired alveolar pneumonia (CAAP) in children, but it is known that children with sleep-disordered breathing (SDB) experience more respiratory infections. We aimed to assess whether SDB is a risk factor for CAAP in early childhood. METHODS: We conducted a prospective, nested, case-control study assessing children < 5 years old who had been given a diagnosis of CAAP based on World Health Organization radiographic criteria. Demographic and clinical data were collected. SDB symptoms were documented using a structured questionnaire. CAAP study and retrospective sleep laboratory databases were compared. SDB presence and severity were determined by questionnaire and polysomnography (PSG). RESULTS: A total of 14,913 children underwent chest radiography during the study period; 1,546 children with radiographically proven CAAP (58% boys) and 441 control subjects (54% boys) were prospectively enrolled. Frequent snoring was reported in 18.6% vs 2.9% subjects with CAAP and control subjects, respectively (P < .001). The respective figures for subjects with CAAP and control subjects for restless sleep, nocturnal breathing problems, abnormal behavior, and chronic rhinorrhea were 21.6% vs 5.3%, 5% vs 1.4%, 6.4% vs 0.2%, and 12.9% vs 1.8%, (P < .001 for each). Fifty children (3.3%) with CAAP vs three control subjects (0.7%) underwent adenoidectomy (P < .001). PSG diagnosis of obstructive sleep apnea had been established previously in 79 patients (5%) with CAAP vs six (1.3%) of the control subjects (OR, 3.7 [95% CI, 1.6-10.0]; P < .001), with higher severity in patients with CAAP than in control subjects. CONCLUSIONS: SDB is common in children with CAAP and is possibly a predisposing risk factor for CAAP in children < 5 years old. We recommend considering SDB in young children who are given a diagnosis of CAAP. PMID- 22095313 TI - Prevalence of diagnosed sleep apnea among patients with type 2 diabetes in primary care. AB - BACKGROUND: Although up to 90% of patients with type 2 diabetes mellitus (T2DM) have obstructive sleep apnea (OSA), the rate at which primary care providers diagnose OSA in patients with diabetes has not been assessed. METHODS: A retrospective, population-based, multiclinic study was performed to determine the proportion of patients with T2DM managed in primary care clinics who were given a diagnosis of OSA and to identify factors associated with an OSA diagnosis. Electronic health records of adult patients with a diagnosis of T2DM were reviewed for a coexisting diagnosis of OSA, and the diagnostic prevalence of OSA was compared with the expected prevalence. RESULTS: A total of 16,066 patients with diabetes with one or more primary care office visits in 27 primary care ambulatory practices during an 18-month period from 2009 to 2010 were identified. Analysis revealed that 18% of the study population received an OSA diagnosis, which is less than the 54% to 94% prevalence reported previously. The 23% prevalence of OSA among obese study patients was lower than the expected 87% prevalence. In a logistic model, male sex, BMI, several chronic conditions, and lower low-density lipoprotein levels and hemoglobin A1c identified patients more likely to carry an OSA diagnosis (likelihood ratio, chi(2) = 1,713; P < .0001). CONCLUSIONS: Primary care providers underdiagnose OSA in patients with T2DM. Obese men with comorbid chronic health conditions are more likely to receive a diagnosis of OSA. Efforts to improve awareness of the association of OSA with T2DM and to implement OSA screening tools should target primary care physicians. PMID- 22095314 TI - Informatics in radiology: Hesse rendering for computer-aided visualization and analysis of anomalies at chest CT and breast MR imaging. AB - A volume-rendering (VR) technique known as Hesse rendering applies image enhancement filters to three-dimensional imaging volumes and depicts the filter responses in a color-coded fashion. Unlike direct VR, which makes use of intensities, Hesse rendering operates on the basis of shape properties, such that nodular structures in the resulting renderings have different colors than do tubular structures and thus are easily visualized. The renderings are mouse-click sensitive and can be used to navigate to locations of possible anomalies in the original images. Hesse rendering is meant to complement rather than replace conventional section-by-section viewing or VR. Although it is a pure visualization technique that involves no internal segmentation or explicit object detection, Hesse rendering, like computer-aided detection, may be effective for quickly calling attention to points of interest in large stacks of images and for helping radiologists to avoid oversights. PMID- 22095315 TI - Quality initiatives: Establishing an interventional radiology patient radiation safety program. AB - The Interventional Radiology Patient Radiation Safety Program was created to better educate patients who are scheduled to undergo high-dose interventional radiologic procedures about the risks of radiation, better monitor the delivered doses, and reduce the risk for deterministic effects. The program combines preprocedure evaluation and counseling, intraprocedure monitoring, and postprocedure documentation and counseling with the guidelines of the National Cancer Institute and the Society of Interventional Radiology. Between July 2009, when the program was implemented, and September 2010, over 3500 interventional radiologic procedures were monitored and documented, and 63 procedures with an adjusted cumulative dose of more than 3 Gy were identified and further analyzed; four procedures were found to be outside the control limits. Additional review of these four procedures resulted in practice modifications. Anecdotal feedback from physician assistants and attending physicians indicated that the program had another positive effect: Patients who required postprocedure counseling about the potential for radiation-induced skin injuries were no longer surprised by this information. Implementation of this program is straightforward, requires little infrastructure and few resources, and may be applied in most interventional radiology practices. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.321115002/-/DC1. PMID- 22095316 TI - Comparison of four mathematical models to analyze indicator-dilution curves in the coronary circulation. AB - While several models have proven to result in accurate estimations when measuring cardiac output using indicator dilution, the mono-exponential model has primarily been chosen for deriving coronary blood/plasma volume. In this study, we compared four models to derive coronary plasma volume using indicator dilution; the mono exponential, power-law, gamma-variate, and local density random walk (LDRW) model. In anesthetized goats (N = 14), we determined the distribution volume of high molecular weight (2,000 kDa) dextrans. A bolus injection (1.0 ml, 0.65 mg/ml) was given intracoronary and coronary venous blood samples were taken every 0.5-1.0 s; outflow curves were analyzed using the four aforementioned models. Measurements were done at baseline and during adenosine infusion. Absolute coronary plasma volume estimates varied by ~25% between models, while the relative volume increase during adenosine infusion was similar for all models. The gamma-variate, LDRW, and mono-exponential model resulted in volumes corresponding with literature, whereas the power-model seemed to overestimate the coronary plasma volume. The gamma-variate and LDRW model appear to be suitable alternative models to the mono-exponential model to analyze coronary indicator dilution curves, particularly since these models are minimally influenced by outliers and do not depend on data of the descending slope of the curve only. PMID- 22095317 TI - The Nightingale Prize 2011 for best MBEC paper in 2010. PMID- 22095318 TI - Comparison of early and late images on 123I-iomazenil SPECT with cerebral blood flow and oxygen extraction fraction images on PET in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease. AB - OBJECTIVE: The aim of the present study was to determine whether early and late/early images on 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) correlate with cerebral blood flow (CBF) images and oxygen extraction fraction (OEF) images on PET, respectively, in the cerebral cortex of patients with chronic unilateral middle cerebral artery or internal carotid artery occlusive disease. METHODS: In 20 normal individuals and in 68 patients, CBF and OEF were assessed using 15O-PET, and brain SPECT scans were initiated immediately after (early images) and 180 min after (late images) the administration of 123I-IMZ. A region of interest was automatically placed in the middle cerebral artery territory in both cerebral hemispheres using a three dimensional stereotaxic region of interest template, and the ratio of the value in the affected side to that in the contralateral side was calculated in each image. RESULTS: Among patients, a significant positive correlation was observed between PET-CBF ratios and the SPECT-early IMZ ratios (r=0.797, P<0.0001) as well as between the PET-OEF ratios and the SPECT-late/early IMZ ratios (r=0.679, P<0.0001). When an abnormally elevated PET-OEF ratio was defined as a value greater than the mean+2 SD obtained in normal participants, the SPECT-late/early IMZ ratios yielded 100% sensitivity and 93% specificity, with 76% positive predictive and 100% negative-predictive values for detecting abnormally elevated PET-OEF ratios. CONCLUSION: Early and late/early images on 123I-IMZ SPECT correlate with CBF images and OEF images on PET, respectively, in the cerebral cortex of patients with chronic unilateral major cerebral artery occlusive disease. PMID- 22095319 TI - Comparing the Finapres and Caretaker systems for measuring pulse transit time before and after exercise. AB - We aimed to compare the Finapres system, which is designed for accurate intra arterial amplitude measurement, to the Caretaker system, which is designed for temporal accuracy of intra-arterial measurement, in regard to measurement of pulse transit time (PTT) at baseline and following an endurance exercise session. Pulse transit time was evaluated between the R-wave of the ECG and the foot of the arterial waveform using either the Finapres (fpPTT) or Caretaker (ctPTT). 23 participants were measured before and after completion of endurance exercise. When comparing PTT values before and after an exercise intervention within devices, ctPTT was significantly different following exercise (P=0.03); however, the Finapres obtained values did not differ significantly. Before exercise, there was no significant relationship between devices, however, after exercise a significant moderate correlation was observed (r=0.45, P=0.02). Significant differences existed between ctPTT and fpPTT (P< 0.001). The Caretaker system appears to be more accurate at detecting changes in PTT occurring as a result of a single aerobic exercise session. This may be due to the servo-controller feedback loop in the waveform contour predicting algorithm within the Finapres system, which is not present in the Caretaker unit. The Finapres system also appears to have an inherent delay in pulse contour reporting. PMID- 22095320 TI - Is EMG of the lower leg dependent on weekly running mileage? AB - Neuromuscular activity of the lower leg is dependent on the task performed, speed of movement and gender. Whether training volume influences neuromuscular activity is not known. The EMG of physically active persons differing in running mileage was analysed to investigate this. 55 volunteers were allocated to a low (LM: < 30 km), intermediate (IM: > 30 km & < 45 km) or high mileage (HM: > 45 km) group according to their weekly running volume. Neuromuscular activity of the lower leg was measured during running (3.33 m.s - 1). Mean amplitude values for preactivation, weight acceptance and push-off were calculated and normalised to the mean activity of the entire gait cycle.Higher activity in the gastrocnemius group was observed in weight acceptance in LM compared to IM (+30%) and HM (+25%) but lower activity was present in the push-off for LM compared to IM and HM. For the peroneal muscle, differences were present in the push-off where HM showed increased activity compared to IM (+24%) and LM (+60%). The tibial muscle revealed slightly lower activity during preactivation for the high mileage runners. Neuromuscular activity differs during stance between the high and intermediate group compared to low mileage runners. Slight adaptations in neuromuscular activation indicate a more target-oriented activation strategy possibly due to repetitive training in runners with higher weekly mileage. PMID- 22095321 TI - Sport and oxidative stress in oncological patients. AB - Oxidative stress is thought to be an important factor in the onset, progression and recurrence of cancer. In order to investigate how it is influenced by physical activity, we measured oxidative stress and antioxidative capacity (aoC) in 12 women with breast cancer and 6 men with prostate cancer, before and after long hiking trips. Before the hike, the men had a ROS-concentration of 1.8+/-0.6 mM H2O2 and an aoC of 0.7+/-0.6 mM Trolox-equivalent (Tro), while the women had a ROS-concentration of 3.1+/-0.7 mM H2O2 and an aoC of 1.2+/-0.2 mM Tro. After the hike, women showed no significant change in ROS and a significant increase in aoC (1.3+/-0.2 mM Tro), while the ROS concentration in men increased significantly (2.1+/-0.3 mM H2O2) and their aoC decreased (0.25+/-0.1 mM Tro). After a regenerative phase, the ROS concentration of the men decreased to 1.7+/-0.4 mM H2O2 and their aoC recovered significantly (1.2+/-0.4 mM Tro), while the women presented no significant change in the concentration of H2O2 but showed an ulterior increase in antioxidant capacity (2.05+/-0.43 mM Tro). From this data we conclude that physical training programs as for example long distance hiking trips can improve the aoC in the blood of oncological patients. PMID- 22095323 TI - ENT function in a 14-days guinness scuba dive. AB - Scuba diving is known to affect the rhino-pharyngo-tubaric district (RPT unit). The aim of the study was to document function modifications of the RPT unit in 6 Italian divers (3 men and 3 women) who lived for 14 days consecutively at a depth of 8-10 m, breathing air (21% oxygen) at a pressure ranging between 1.8 and 2 ATA. RPT and inner ear assessment were carried out before the dive (TIME 0) and 24 h (TIME 1) after resurfacing, in order to investigate diving-related RPT and inner ear alterations. Physical examination after resurfacing revealed: fungal external otitis, otoscopic findings consistent with middle ear barotraumas and rhinosinusitis. Rhino-manometry showed a remarkable increase in inspiratory nasal flow and a substantial decrease in nasal resistance. No epithelial cell disruption was retrieved comparing pre and post resurfacing samples. Post-diving tubaric dysfunction was found. Pure tone audiometry revealed a bilateral 40 dB HL hearing loss at 4 kHz in 1 diver. Relevant PTA functions did not seem to be affected by the experiment, no remarkable changes were found at the Sensory Organisation Test and at the Motor Control Test. The 14-day underwater period had a positive effect on nasal flows and resistances. PMID- 22095322 TI - Exercise training improves vasoreactivity in the knee artery. AB - Physical activity has been shown to enhance endothelial function of central and peripheral vascular beds. The primary purpose of the present study was to test the hypothesis that a short-term exercise training program would result in enhanced endothelium-dependent vasorelaxation of a major artery supplying blood flow to the knee joint, the middle genicular artery. Female Yucatan miniature swine were randomly assigned into exercise trained (n=7) or sedentary (n=7) groups. Exercise trained pigs underwent a daily exercise training program on treadmills for 7 days. In vitro assessment of vasorelaxation was determined in a dose response manner by administrating increasing doses of 3 different dilators; adenosine diphosphate, bradykinin, and sodium nitroprusside. The role of nitric oxide synthase and cyclooxygenase pathways in vasomotor responses was evaluated with specific inhibitors using nitro-L-arginine methyl ester and indomethacin incubation, respectively. The results of this investigation indicate that adenosine and bradykinin-induced endothelium-dependent vasorelaxation were significantly enhanced in middle genicular artery from exercise trained pigs (p<0.05). Endothelium-independent vasorelaxation was not altered with exercise training as determined by the response to sodium nitroprusside. The findings of the present investigation indicate that short-term exercise training enhances endothelial function of middle genicular artery through adaptations in the nitric oxide synthase and by non-nitric oxide synthase, non-cyclooxygenase pathways. PMID- 22095324 TI - Reliability of a high-intensity endurance cycling test. AB - This study assessed the reproducibility of performance and selected metabolic variables during a variable high-intensity endurance cycling test. 8 trained male cyclists (age: 35.9 +/- 7.7 years, maximal oxygen uptake: 54.3 +/- 3.9 mL.kg - 1.min - 1) completed 4 high-intensity cycling tests, performed in consecutive weeks. The protocol comprised: 20 min of progressive incremental exercise, where the power output was increased by 5% maximal workload (Wmax) every 5 min from 70% Wmax to 85% Wmax; ten 90 s bouts at 90% Wmax, separated by 180 s at 55% Wmax; 90% Wmax until volitional exhaustion. Blood samples were drawn and heart rate was monitored throughout the protocol. There was no significant order effect between trials for time to exhaustion (mean: 4 113.0 +/- 60.8 s) or total distance covered (mean: 4 6126.2 +/- 1 968.7 m). Total time to exhaustion and total distance covered showed very high reliability with a mean coefficient of variation (CV) of 1.6% (95% Confidence Intervals (CI) 0.0 +/- 124.3 s) and CV of 2.2% (95% CI 0.0 +/- 1904.9 m), respectively. Variability in plasma glucose concentrations across the time points was very small (CV 0.46-4.3%, mean 95% CI 0.0 +/- 0.33 to 0.0 +/- 0.94 mmol.L - 1). Plasma lactate concentrations showed no test order effect. The reliability of performance and metabolic variables makes this protocol a valid test to evaluate nutritional interventions in endurance cycling. PMID- 22095325 TI - MMP(-2) expression in skeletal muscle after strength training. AB - The aim of this study was to assess the effects of resistance training on ladders (RTL) on MMP(-2) expression and blood lactate concentration [La-]. 30 male (3 months of age), albino rats were divided into 3 groups: sedentary control (SC, n=10), low resistance exercise training (Low-IntRT, n=10) and high-intensive exercise training (High-IntRT, n=10). Animals of High-IntRT were submitted to a progressively increasing overload in relation to body weight until exhaustion, while the Low-IntRT group performed the same exercise regimen with no external load. The program had a frequency of 3 times per week over 8 weeks. MMP(-2) expression of tibialis anterior muscle and [La-] were measured. While there was a significant increase of MMP(-2) (pro-form) in both groups, only High-IntRT significantly increased MMP(-2) in active-form (p<0.05). Both trained groups exhibited an increase in [La-] when compared to controls, however, the increase in [La-] was significantly higher in the High-IntRT compared to Low-IntRT (p<0.05). Strong correlation was found between MMP(-2) (active form) and [La-] in High-IntRT (r=0.91). RTL in using low and high-intensity exercise can serve as a model to demonstrate different responses of MMP(-2) expression in an animal model. It appears active form expression of MMP(-2) is modulated by exercise intensity. PMID- 22095326 TI - Influence of acute eccentric exercise on the H:Q ratio. AB - The purpose of the present study was to examine the effects of an acute bout of eccentric exercise on maximal isokinetic concentric peak torque (PT) of the leg flexors and extensors and the hamstrings-to-quadriceps (H:Q) strength ratio. Sixteen male (mean+/-SD: age=20.9+/-2 years; stature=177.0+/-4.4 cm; mass=76.8+/ 10.0 kg) volunteers performed maximal, concentric isokinetic leg extension and flexion muscle actions at 60 degrees .sec - 1 before and after (24-72 h) a bout of eccentric exercise. The eccentric exercise protocol consisted of 4 sets of 10 repetitions for the leg press, leg extension, and leg curl exercises at 120% of the concentric one repetition maximum (1-RM). The results indicated that the acute eccentric exercise protocol resulted in a significant (P<0.05) decrease in isokinetic leg flexion (13-19%) and leg extension (11-16%) PT 24-72 h post exercise. However, the H:Q ratios were unaltered by the eccentric exercise protocol. These findings suggest that an acute bout of eccentric exercise utilizing both multi - and single - joint dynamic constant external resistance (DCER) exercises results in similar decreases in maximal isokinetic strength of the leg flexors and extensors, but does not alter the H:Q ratio. PMID- 22095327 TI - Hypogonadism and anemia in an athlete. AB - We report the case of a highly trained endurance athlete (22-year-old) who developed anemia (Hb 9.5 mg/dl) over a period of 6 months. Iron deficient or haemolytic anemia, as well as chronic loss of blood, were excluded. Further, laboratory analyses revealed that this athlete exhibited very low levels of testosterone due to a partial hypogonadotropic hypogonadism. Following testosterone supplementation, red blood cell indices improved. Although hypogonadotropic hypogonadism is well known to be associated with reduced hematopoesis, it rarely causes anemia in athletes. This should be considered as a possible cause for anemia. Extreme training, unbalanced nutrition or the combination of both, have been shown to be causally involved in the development of secondary hypogonadotropic hypogonadism. PMID- 22095328 TI - Movement demands and match performance in professional Australian football. AB - This study examined the relationship between coaches' perception of match performance and movement demands in Australian Football. Movement demands were collected from 21 professional players over 12 matches during one Australian Football League season, with 69 player files collected. Additionally, match events relative to playing time and distance covered, along with player physical characteristics were collected. Based on coaches subjective rating of match performance (out of 20), relatively high calibre (HC) players (>= 15/20) were compared with relatively low calibre (LC) players (<= 9/20) for all variables. The HC players were older (+17%, p=0.011), spent a greater percentage of time performing low-speed running (+2%, p=0.039), had more kicks (38%, p=0.001) and disposals (35%, p=0.001) per min and covered less distance per kick (- 50%, p=0.001) and disposal (- 44%, p=0.001) than the LC group, with the effect sizes also supporting this trend. Further, HC players covered less distance (- 14%, p=0.037), spent less percentage of time (- 17%, p=0.037) and performed fewer (- 9%, p=0.026) efforts per min high-speed running than LC players, which was further confirmed by the effect sizes. Movement demands and match events are related to coaches' perception of match performance in professional Australian Football. Further, high levels of involvement with the football appeared to be more important to performance than high exercise speed. PMID- 22095329 TI - Haemophilia and exercise. AB - One of the most important objectives of intervention programs for persons with haemophilia (PWH) is to improve their quality of life. Regular physical activity has been recommended as an adjunct to conventional treatment, with positive results in the prevention of joint problems and bleeding, in addition to the improvement in cardiovascular function, muscle strength, and body composition. The objective of the present review was to present the benefits of aerobic and resistance training programs in PWH, as well to discuss the best exercise dose response in the different levels of disease severity. We considered randomized controlled trials, study cases and literature reviews from MEDLINE and Highwire databases. After a detailed analysis of the studies involving exercise for PWH, it can be concluded that this intervention elicits some benefits for physical fitness and blood coagulation mechanisms, suggesting the application of physical training as a non pharmacological treatment in association with conventional treatment. Adequate and periodized resistance training considering the disease severity, accompanied by physical education professionals could improve muscle strength, balance and proprioception. In addition, aerobic training could reduce the risks of obesity and several metabolic and cardiovascular diseases. Exercise can improve several outcomes of quality in PWH. PMID- 22095330 TI - Global alcohol producers, science, and policy: the case of the International Center for Alcohol Policies. AB - In this article, I document strategies used by alcohol producers to influence national and global science and policy. Their strategies include producing scholarly publications with incomplete, distorted views of the science underlying alcohol policies; pressuring national and international governmental institutions; and encouraging collaboration of public health researchers with alcohol industry-funded organizations and researchers. I conclude with a call for an enhanced research agenda drawing on sources seldom used by public health research, more focused resourcing of global public health bodies such as the World Health Organization to counterbalance industry initiatives, development of technical assistance and other materials to assist countries with effective alcohol-control strategies, and further development of an ethical stance regarding collaboration with industries that profit from unhealthy consumption of their products. PMID- 22095331 TI - Inventing conflicts of interest: a history of tobacco industry tactics. AB - Confronted by compelling peer-reviewed scientific evidence of the harms of smoking, the tobacco industry, beginning in the 1950s, used sophisticated public relations approaches to undermine and distort the emerging science. The industry campaign worked to create a scientific controversy through a program that depended on the creation of industry-academic conflicts of interest. This strategy of producing scientific uncertainty undercut public health efforts and regulatory interventions designed to reduce the harms of smoking. A number of industries have subsequently followed this approach to disrupting normative science. Claims of scientific uncertainty and lack of proof also lead to the assertion of individual responsibility for industrially produced health risks. PMID- 22095332 TI - Changing perceptions: of pandemic influenza and public health responses. AB - According to the latest World Bank estimates, over the past decade some US $4.3 billion has been pledged by governments to combat the threat of pandemic influenza. Presidents, prime ministers, and even dictators the world over have been keen to demonstrate their commitment to tackling this disease, but this has not always been the case. Indeed, government-led intervention in responding to the threat of pandemic influenza is a relatively recent phenomenon. I explore how human understandings of influenza have altered over the past 500 years and how public policy responses have shifted accordingly. I trace the progress in human understanding of causation from meteorological conditions to the microscopic, and how this has prompted changes in public policy to mitigate the disease's impact. I also examine the latest trend of viewing pandemic influenza as a security threat and how this has changed contemporary governance structures and power dynamics. PMID- 22095333 TI - Sugar-sweetened beverage taxes in Brazil. AB - OBJECTIVES: We investigated whether taxing sugar-sweetened beverages (SSBs) would improve the diets of households in Brazil. METHODS: We used household food consumption data that the Brazilian Institute of Geography and Statistics collected in 2002-2003 from a nationally representative sample of 48,470 Brazilian households. The consumption of SSBs is expressed as the total SSB calories consumed and as the SSB percentage of the total calories purchased. We investigated price elasticity with regression models, controlling for demographic variables, income, and prices of all other foods and drinks. RESULTS: Increases in the price of SSBs led to reductions in consumption. A 1.00% increase in the price of SSBs led to a 0.85% reduction of SSB calories consumed (1.03% reduction for the poor and 0.63% for the nonpoor). Increased income had a positive effect on SSB consumption, but the effect was less than half the size of the price elasticity (0.41% increase in SSB calories consumed for every 1.00% increase in income). CONCLUSIONS: High SSB price elasticity in Brazil indicates that a tax on purchased weight or volume would lead to reductions in SSB consumption. PMID- 22095334 TI - Consequences of industry relationships for public health and medicine. PMID- 22095335 TI - Promoting transparency in pharmaceutical industry-sponsored research. AB - Strong, evidence-based practice requires that objective, unbiased research be available to inform individual clinical decisions, systematic reviews, meta analyses, and expert guideline recommendations. Industry has used seeding trials, publication planning, messaging, ghostwriting, and selective publication and reporting of trial outcomes to distort the medical literature and undermine clinical trial research by obscuring information relevant to patients and physicians. Policies that promote transparency in the clinical trial research process, through improved and expanded disclosure of investigator contributions and funding, comprehensive publicly available trial registration, and independent analysis of clinical trial data analysis may address these subversive practices by improving accountability among industry and investigators. Minimizing marketing's impact on clinical trial research and strengthening the science will protect medical literature's integrity and the public's health. PMID- 22095337 TI - Sexual satisfaction and health are positively associated with penile-vaginal intercourse but not other sexual activities. PMID- 22095336 TI - Social gradients in the health of Indigenous Australians. AB - The pattern of association between socioeconomic factors and health outcomes has primarily depicted better health for those who are higher in the social hierarchy. Although this is a ubiquitous finding in the health literature, little is known about the interplay between these factors among indigenous populations. We begin to bridge this knowledge gap by assessing evidence on social gradients in indigenous health in Australia. We reveal a less universal and less consistent socioeconomic status patterning in health among Indigenous Australians, and discuss the plausibility of unique historical circumstances and social and cultural characteristics in explaining these patterns. A more robust evidence base in this field is fundamental to processes that aim to reduce the pervasive disparities between indigenous and nonindigenous population health. PMID- 22095338 TI - Ethical justification for conducting public health surveillance without patient consent. AB - Public health surveillance by necessity occurs without explicit patient consent. There is strong legal and scientific support for maintaining name-based reporting of infectious diseases and other types of public health surveillance. We present conditions under which surveillance without explicit patient consent is ethically justifiable using principles of contemporary clinical and public health ethics. Overriding individual autonomy must be justified in terms of the obligation of public health to improve population health, reduce inequities, attend to the health of vulnerable and systematically disadvantaged persons, and prevent harm. In addition, data elements collected without consent must represent the minimal necessary interference, lead to effective public health action, and be maintained securely. PMID- 22095339 TI - Joe Camel in a bottle: Diageo, the Smirnoff brand, and the transformation of the youth alcohol market. AB - I have documented the shift in youth alcoholic beverage preference from beer to distilled spirits between 2001 and 2009. I have assessed the role of distilled spirits industry marketing strategies to promote this shift using the Smirnoff brand marketing campaign as a case example. I conclude with a discussion of the similarities in corporate tactics across consumer products with adverse public health impacts, the importance of studying corporate marketing and public relations practices, and the implications of those practices for public health. PMID- 22095340 TI - Operationalization of community-based participatory research principles: assessment of the national cancer institute's community network programs. AB - OBJECTIVES: We examined how National Cancer Institute-funded Community Network Programs (CNPs) operationalized principles of community-based participatory research (CBPR). METHODS: We reviewed the literature and extant CBPR measurement tools. On the basis of that review, we developed a 27-item questionnaire for CNPs to self-assess their operationalization of 9 CBPR principles. Our team comprised representatives of 9 of the National Cancer Institute's 25 CNPs. RESULTS: Of the 25 CNPs, 22 (88%) completed the questionnaire. Most scored well on CBPR principles of recognizing community as a unit of identity, building on community strengths, facilitating colearning, embracing iterative processes in developing community capacity, and achieving a balance between data generation and intervention. CNPs varied in the extent to which they employed CBPR principles of addressing determinants of health, sharing power among partners, engaging the community in research dissemination, and striving for sustainability. CONCLUSIONS: Although the development of assessment tools in this field is in its infancy, our findings suggest that fidelity to CBPR processes can be assessed in a variety of settings. PMID- 22095341 TI - Changes in fluoroquinolone use for gonorrhea following publication of revised treatment guidelines. AB - OBJECTIVES: We evaluated the impact of revised national treatment recommendations on fluoroquinolone use for gonorrhea in selected states. METHODS: We evaluated gonorrhea cases reported through the Sexually Transmitted Disease Surveillance Network as treated between July 1, 2006 and May 31, 2008, using interrupted time series analysis. Outcomes were fluoroquinolone treatment overall, by area, and by practice setting. RESULTS: Of 16,126 cases with treatment dates in this period, 15,669 noted the medication used. After revised recommendations were released, fluoroquinolone use decreased abruptly overall (21.5%; 95% confidence interval [CI] = 15.9%, 27.2%), in most geographic areas evaluated, and in sexually transmitted disease clinics (28.5%; 95% CI = 19.0%, 37.9%). More gradual decreases were seen in primary care (8.6%; 95% CI = 2.6%, 14.6%), and in emergency departments, urgent care, and hospitals (2.7%; 95% CI = 1.7%, 3.7%). CONCLUSIONS: Fluoroquinolone use decreased after the publication of revised national guidelines, particularly in sexually transmitted disease clinics. Additional mechanisms are needed to increase the speed and magnitude of changes in prescribing in primary care, emergency departments, urgent care, and hospitals. PMID- 22095342 TI - Core competencies for doctoral education in public health. AB - The Association of Schools of Public Health (ASPH) released the Doctor of Public Health (DrPH) Core Competency Model in 2009. Between 2007 and 2009, a national expert panel with members of the academic and practice communities guided by the ASPH Education Committee developed its 7 performance domains, including 54 competencies. We provide an overview and analysis of the challenges and issues associated with the variability in DrPH degree offerings, reflect on the model development process and related outcomes, and discuss the significance of the model, future applications, and challenges for integration across educational settings. With the model, ASPH aims to stimulate national discussion on the competencies needed by DrPH graduates with the new challenges of 21st-century public health practice and to better define the DrPH degree. PMID- 22095343 TI - Cyberbullying, school bullying, and psychological distress: a regional census of high school students. AB - OBJECTIVES: Using data from a regional census of high school students, we have documented the prevalence of cyberbullying and school bullying victimization and their associations with psychological distress. METHODS: In the fall of 2008, 20,406 ninth- through twelfth-grade students in MetroWest Massachusetts completed surveys assessing their bullying victimization and psychological distress, including depressive symptoms, self-injury, and suicidality. RESULTS: A total of 15.8% of students reported cyberbullying and 25.9% reported school bullying in the past 12 months. A majority (59.7%) of cyberbullying victims were also school bullying victims; 36.3% of school bullying victims were also cyberbullying victims. Victimization was higher among nonheterosexually identified youths. Victims report lower school performance and school attachment. Controlled analyses indicated that distress was highest among victims of both cyberbullying and school bullying (adjusted odds ratios [AORs] were from 4.38 for depressive symptoms to 5.35 for suicide attempts requiring medical treatment). Victims of either form of bullying alone also reported elevated levels of distress. CONCLUSIONS: Our findings confirm the need for prevention efforts that address both forms of bullying and their relation to school performance and mental health. PMID- 22095344 TI - Temporal and regional trends in the prevalence of healthy lifestyle characteristics: United States, 1994-2007. AB - OBJECTIVES: We examined temporal and regional trends in the prevalence of health lifestyles in the United States. METHODS: We used 1994 to 2007 data from the Behavioral Risk Factor Surveillance System to assess 4 healthy lifestyle characteristics: having a healthy weight, not smoking, consuming fruits and vegetables, and engaging in physical activity. The concurrent presence of all 4 characteristics was defined as a healthy overall lifestyle. We used logistic regression to assess temporal and regional trends. RESULTS: The percentages of individuals who did not smoke (4% increase) and had a healthy weight (10% decrease) showed the strongest temporal changes from 1994 to 2007. There was little change in fruit and vegetable consumption or physical activity. The prevalence of healthy lifestyles increased minimally over time and varied modestly across regions; in 2007, percentages were higher in the Northeast (6%) and West (6%) than in the South (4%) and Midwest (4%). CONCLUSIONS: Because of the large increases in overweight and the declines in smoking, there was little net change in the prevalence of healthy lifestyles. Despite regional differences, the prevalence of healthy lifestyles across the United States remains very low. PMID- 22095345 TI - Against the very idea of the politicization of public health policy. AB - I criticize the concern over the politicization of public health policy as a justification for preferring a narrow to a broad model of public health. My critique proceeds along 2 lines. First, the fact that administrative structures and actors are primary sources of public health policy demonstrates its inescapably political and politicized nature. Second, historical evidence shows that public health in Great Britain and the United States has from its very inception been political and politicized. I conclude by noting legitimate ethical concerns regarding the political nature of public health policy and argue that open deliberation in a democratic social order is best served by acknowledging the constraints of the inescapably politicized process of public health policymaking. PMID- 22095346 TI - Wellness incentives, equity, and the 5 groups problem. AB - Wellness incentives are an increasingly popular means of encouraging participation in prevention programs, but they may not benefit all groups equally. To assist those planning, conducting, and evaluating incentive programs, I describe the impact of incentives on 5 groups: the "lucky ones," the "yes-I-can" group, the "I'll-do-it-tomorrow" group, the "unlucky ones," and the "leave-me-alone" group. The 5 groups problem concerns the question of when disparities in the capacity to use incentive programs constitute unfairness and how policymakers ought to respond. I outline 4 policy options: to continue to offer incentives universally, to offer them universally but with modifications, to offer targeted rather than universal programs, and to abandon incentive programs altogether. PMID- 22095347 TI - Is social clustering of obesity due to social contagion or genetic transmission? PMID- 22095348 TI - Hispanic lesbians and bisexual women at heightened risk for [corrected] health disparities. AB - OBJECTIVES: We investigated whether elevated risks of health disparities exist in Hispanic lesbians and bisexual women aged 18 years and older compared with non Hispanic White lesbians and bisexual women and Hispanic heterosexual women. METHODS: We analyzed population-based data from the Washington State Behavioral Risk Factor Surveillance System (2003-2009) using adjusted logistic regressions. RESULTS: Hispanic lesbians and bisexual women, compared with Hispanic heterosexual women, were at elevated risk for disparities in smoking, asthma, and disability. Hispanic bisexual women also showed higher odds of arthritis, acute drinking, poor general health, and frequent mental distress compared with Hispanic heterosexual women. In addition, Hispanic bisexual women were more likely to report frequent mental distress than were non-Hispanic White bisexual women. Hispanic lesbians were more likely to report asthma than were non-Hispanic White lesbians. CONCLUSIONS: The elevated risk of health disparities in Hispanic lesbians and bisexual women are primarily associated with sexual orientation. Yet, the elevated prevalence of mental distress for Hispanic bisexual women and asthma for Hispanic lesbians appears to result from the cumulative risk of doubly disadvantaged statuses. Efforts are needed to address unique health concerns of diverse lesbians and bisexual women. PMID- 22095349 TI - Who will deliver on the promise? AB - The Doctor of Public Health (DrPH) Core Competency Model aspires to rigorously train future leaders of public health practice to direct and advance societal efforts that address socially rooted causes of health and illness. Although there is no proven formula for success, 3 principles derived from practice may guide the way forward: (1) institutionalize mutual learning and reciprocity between schools of public health and public health agencies and organizations, (2) capitalize on the full resources of the larger university to enrich the educational experiences of DrPH candidates and public health leaders, and (3) globalize the search for model DrPH programs that may be adapted for US schools. Schools of public health must ensure that DrPH programs gain the status and resources needed to fulfill their societal mandate. PMID- 22095351 TI - Evaluating the safety effects of bicycle lanes in New York City. AB - OBJECTIVES: We evaluated the effects of on-street bicycle lanes installed prior to 2007 on different categories of crashes (total crashes, bicyclist crashes, pedestrian crashes, multiple-vehicle crashes, and injurious or fatal crashes) occurring on roadway segments and at intersections in New York City. METHODS: We used generalized estimating equation methodology to compare changes in police reported crashes in a treatment group and a comparison group before and after installation of bicycle lanes. Our study approach allowed us to control confounding factors, such as built environment characteristics, that cannot typically be controlled when a comparison group is used. RESULTS: Installation of bicycle lanes did not lead to an increase in crashes, despite the probable increase in the number of bicyclists. The most likely explanations for the lack of increase in crashes are reduced vehicular speeds and fewer conflicts between vehicles and bicyclists after installation of these lanes. CONCLUSIONS: Our results indicate that characteristics of the built environment have a direct impact on crashes and that they should thus be controlled in studies evaluating traffic countermeasures such as bicycle lanes. To prevent crashes at intersections, we recommend installation of "bike boxes" and markings that indicate the path of bicycle lanes across intersections. PMID- 22095350 TI - Position-specific HIV risk in a large network of homeless youths. AB - OBJECTIVES: We examined interconnections among runaway and homeless youths (RHYs) and how aggregated network structure position was associated with HIV risk in this population. METHODS: We collected individual and social network data from 136 RHYs. On the basis of these data, we generated a sociomatrix, accomplished network visualization with a "spring embedder," and examined k-cores. We used multivariate logistic regression models to assess associations between peripheral and nonperipheral network position and recent unprotected sexual intercourse. RESULTS: Small numbers of nominations at the individual level aggregated into a large social network with a visible core, periphery, and small clusters. Female youths were more likely to be in the core, as were youths who had been homeless for 2 years or more. Youths at the periphery were less likely to report unprotected intercourse and had been homeless for a shorter duration. CONCLUSIONS: HIV risk was a function of risk-taking youths' connections with one another and was associated with position in the overall network structure. Social network-based prevention programs, young women's housing and health programs, and housing-first programs for peripheral youths could be effective strategies for preventing HIV among this population. PMID- 22095352 TI - Beyond base pairs to bedside: a population perspective on how genomics can improve health. AB - A decade after the sequencing of the human genome, the National Human Genome Research Institute announced a strategic plan for genomic medicine. It calls for evaluating the structure and biology of genomes, understanding the biology of disease, advancing the science of medicine, and improving the effectiveness of health care. Fulfilling the promise of genomics urgently requires a population perspective to complement the bench-to-bedside model of translation. A population approach should assess the contribution of genomics to health in the context of social and environmental determinants of disease; evaluate genomic applications that may improve health care; design strategies for integrating genomics into practice; address ethical, legal, and social issues; and measure the population health impact of new technologies. PMID- 22095353 TI - The impact of workplace policies and other social factors on self-reported influenza-like illness incidence during the 2009 H1N1 pandemic. AB - OBJECTIVES: We assessed the impact of social determinants of potential exposure to H1N1--which are unequally distributed by race/ethnicity in the United States- on incidence of influenza-like illness (ILI) during the 2009 H1N1 pandemic. METHODS: In January 2010 we surveyed a nationally representative sample (n = 2079) of US adults from the Knowledge Networks online research panel, with Hispanic and African American oversamples. The completion rate was 56%. RESULTS: Path analysis examining ILI incidence, race, and social determinants of potential exposure to H1N1 demonstrated that higher ILI incidence was related to workplace policies, such as lack of access to sick leave, and structural factors, such as number of children in the household. Hispanic ethnicity was related to a greater risk of ILI attributable to these social determinants, even after we controlled for income and education. CONCLUSIONS: The absence of certain workplace policies, such as paid sick leave, confers a population-attributable risk of 5 million additional cases of ILI in the general population and 1.2 million cases among Hispanics. Federal mandates for sick leave could have significant health impacts by reducing morbidity from ILI, especially in Hispanics. PMID- 22095354 TI - Transgender health in Massachusetts: results from a household probability sample of adults. AB - Despite higher rates of unemployment and poverty among transgender adults (n = 131; 0.5% weighted) than among nontransgender adults (n = 28,045) in our population-based Massachusetts household sample, few health differences were observed between transgender and nontransgender adults. Transgender adults who are stably housed and participated in a telephone health survey may represent the healthiest segment of the transgender population. Our findings demonstrate a need for diverse sampling approaches to monitor transgender health, including adding transgender measures to population-based surveys, and further highlight economic inequities that warrant intervention. PMID- 22095355 TI - A decade of spore-forming bacterial infections among European injecting drug users: pronounced regional variation. AB - The recent anthrax outbreak among injecting drug users (IDUs) in Europe has highlighted an ongoing problem with severe illness resulting from spore-forming bacteria in IDUs. We collated the numbers of cases of 4 bacterial illnesses (botulism, tetanus, Clostridium novyi, and anthrax) in European IDUs for 2000 to 2009 and calculated population rates. Six countries reported 367 cases; rates varied from 0.03 to 7.54 per million people. Most cases (92%) were reported from 3 neighboring countries: Ireland, Norway, and the United Kingdom. This geographic variation needs investigation. PMID- 22095356 TI - Disability among lesbian, gay, and bisexual adults: disparities in prevalence and risk. AB - OBJECTIVES: We used population-based data to comprehensively examine disability among lesbian, gay, and bisexual adults. METHODS: We estimated prevalence of disability and its covariates and compared by sexual orientation by utilizing data from the Washington State Behavioral Risk Factor Surveillance System (n = 82,531) collected in 2003, 2005, 2007, and 2009. We used multivariate logistic regression to examine the relationship between disability and sexual orientation, after we controlled for covariates of disability. RESULTS: Findings indicated that the prevalence of disability is higher among lesbian, gay, and bisexual adults compared with their heterosexual counterparts; lesbian, gay, and bisexual adults with disabilities are significantly younger than heterosexual adults with disabilities. Higher disability prevalence among lesbians and among bisexual women and men remained significant after we controlled for covariates of disability. CONCLUSIONS: Higher rates of disability among lesbian, gay, and bisexual adults are of major concern. Efforts are needed to prevent, delay, and reduce disabilities as well as to improve the quality of life for lesbian, gay, and bisexual adults with disabilities. Future prevention and intervention efforts need to address the unique concerns of these groups. PMID- 22095357 TI - The future of public health ethics. PMID- 22095358 TI - Sexual compulsivity, co-occurring psychosocial health problems, and HIV risk among gay and bisexual men: further evidence of a syndemic. AB - OBJECTIVES: We evaluated whether sexual compulsivity fits into a syndemic framework, in which sexual compulsivity is one of a number of co-occurring psychosocial health problems that increase HIV risk among men who have sex with men (MSM). METHODS: In 2003 and 2004, we conducted an anonymous cross-sectional survey of MSM in New York City (n = 669) by approaching attendees at gay, lesbian, and bisexual community events. We analyzed data by bivariate and multivariate logistic regression. RESULTS: We found strong positive interrelationships among syndemic factors including sexual compulsivity, depression, childhood sexual abuse, intimate partner violence, and polydrug use. In bivariate analyses, all syndemic health problems except for childhood sexual abuse were positively related to HIV seropositivity and high-risk sexual behavior. Our multivariate models revealed an array of interrelationships among psychosocial health problems. We found amplified effects of these problems on HIV seropositivity and on the likelihood of engaging in high-risk sexual behavior. CONCLUSIONS: Our findings support the conclusion that sexual compulsivity is a component of a syndemic framework for HIV risk among MSM. HIV prevention interventions should consider the overlapping and compounding effects of psychosocial problems, including sexual compulsivity. PMID- 22095359 TI - Health reform and Healthy People initiative. AB - The passage of the Affordable Care Act builds on and strengthens the foundation for prevention and wellness that Healthy People--the nation's health promotion and disease prevention aspirations for a healthier nation--established. The Affordable Care Act reaffirms the themes of Healthy People by promoting population-based prevention and sets the stage for Healthy People 2020. The heart of Healthy People 2010 lies in its leading health indicators, reflecting high priority health issues for the nation. National progress requires broad application of the ecological health model. We reviewed the status of each Healthy People 2010 indicator and noted how the Affordable Care Act drives future positive health outcomes using the ecological model of health as a prism for viewing health improvement. PMID- 22095360 TI - Household food insufficiency, financial strain, work-family spillover, and depressive symptoms in the working class: the Work, Family, and Health Network study. AB - OBJECTIVES: We evaluated the association of household-level stressors with depressive symptoms among low-wage nursing home employees. METHODS: Data were collected in 2006 and 2007 from 452 multiethnic primary and nonprimary wage earners in 4 facilities in Massachusetts. We used logistic regression to estimate the association of depressive symptoms with household financial strain, food insufficiency, and work-family spillover (preoccupation with work-related concerns while at home and vice versa). RESULTS: Depressive symptoms were significantly associated with household financial strain (odds ratio [OR] = 1.82; 95% confidence interval [CI] = 1.03, 3.21) and food insufficiency (OR = 2.10; 95% CI = 1.10, 4.18). Among primary earners, stratified analyses showed that food insufficiency was associated with depressive symptoms (OR = 3.60; 95% CI = 1.42, 9.11) but financial strain was not. Among nonprimary wage earners, depressive symptoms correlated with financial strain (OR = 3.65; 95% CI = 1.48, 9.01) and work-family spillover (OR = 3.22; 95% CI = 1.11, 9.35). CONCLUSIONS: Household financial strain, food insufficiency, and work-family spillover are pervasive problems for working populations, but associations vary by primary wage earner status. The prevalence of food insufficiency among full-time employees was striking and might have a detrimental influence on depressive symptoms and the health of working-class families. PMID- 22095361 TI - Hemoglobin A1c as a diagnostic tool: public health implications from an actor network perspective. AB - Public health arguments for collecting hemoglobin A1c (HbA1c) data, particularly in clinical settings, should be reframed to place more emphasis on nonmedical determinants of population health. We compare individual- with population-level interpretations of HbA1c titers. This comparison reveals that public health researchers need to pay close attention to diagnostic tests and their uses, including rhetorical uses. We also synthesize historical and current evidence to map out 2 possible scenarios for the future. In the first scenario, prevention efforts emphasize primary care and focus almost entirely downstream. The second scenario anticipates downstream interventions but also upstream interventions targeting environments. Our analysis adapts actor-network theory to strategic planning and forecasting in public health. PMID- 22095362 TI - The effects of Arkansas master settlement spending on disparities in smoking. AB - OBJECTIVES: We assessed the effect of Master Settlement Agreement (MSA) spending on smoking disparities in Arkansas, which distinguished itself from other states by investing all of its MSA funds in health-related programs. METHODS: In 1996 2009 data from the Behavioral Risk Factor Surveillance System, we specified multivariate logistic models to examine gender and racial/ethnic disparities in smoking rates within Arkansas (a pre-post analysis) and between Arkansas and its 6 neighboring states. RESULTS: Before the MSA programs started in 2001, male Arkansans smoked more than did female Arkansans (P < .05). After the programs, smoking declined significantly among men (but not women), eliminating the gender disparity by 2009. Smoking among men in Arkansas also declined more than it did in neighboring states (P < .05). Hispanics showed a greater decline in smoking than did non-Hispanic Whites in Arkansas (but not in neighboring states). In 2001, Hispanic Arkansans smoked more than did non-Hispanic Whites (P < .05); by 2009, Hispanic Arkansans smoked significantly less than did non-Hispanic Whites (P < .05). CONCLUSIONS: MSA-funded programs were more effective in some segments of the Arkansas population than in others. Policymakers should consider targeting future MSA tobacco control programs to populations most resistant to change. PMID- 22095363 TI - The disabling effect of diseases: a study on trends in diseases, activity limitations, and their interrelationships. AB - OBJECTIVES: Data from the Netherlands indicate a recent increase in prevalence of chronic diseases and a stable prevalence of disability, suggesting that diseases have become less disabling. We studied the association between chronic diseases and activity limitations in the Netherlands from 1990 to 2008. METHODS: Five surveys among noninstitutionalized persons aged 55 to 84 years (n = 54,847) obtained self-reported data on chronic diseases (diabetes, heart disease, peripheral arterial disease, stroke, lung disease, joint disease, back problems, and cancer) and activity limitations (Organisation for Economic Co-operation and Development [OECD] long-term disability questionnaire or 36-item Short Form Health Survey [SF-36]). RESULTS: Prevalence rates of chronic diseases increased over time, whereas prevalence rates of activity limitations were stable (OECD) or slightly decreased (SF-36). Associations between chronic diseases and activity limitations were also stable (OECD) or slightly decreased (SF-36). Surveys varied widely with regard to disease and limitation prevalence rates and the associations between them. CONCLUSIONS: The hypothesis that diseases became less disabling from 1990 to 2008 was only supported by results based on activity limitation data as assessed with the SF-36. Further research on how diseases and disability are associated over time is needed. PMID- 22095364 TI - Repeat syphilis among men who have sex with men in California, 2002-2006: implications for syphilis elimination efforts. AB - OBJECTIVES: We examined rates of and risk factors for repeat syphilis infection among men who have sex with men (MSM) in California. METHODS: We analyzed 2002 to 2006 California syphilis surveillance system data. RESULTS: During the study period, a mean of 5.9% (range: 4.9%-7.1% per year) of MSM had a repeat primary or secondary (PS) syphilis infection within 2 years of an initial infection. There was no significant increase in the annual proportion of MSM with a repeat syphilis infection (P = .42). In a multivariable model, factors associated with repeat syphilis infection were HIV infection (odds ratio [OR] = 1.65; 95% confidence interval [CI] = 1.14, 2.37), Black race (OR = 1.84; 95% CI = 1.12, 3.04), and 10 or more recent sex partners (OR = 1.99; 95% CI = 1.12, 3.50). CONCLUSIONS: Approximately 6% of MSM in California have a repeat PS syphilis infection within 2 years of an initial infection. HIV infection, Black race, and having multiple sex partners are associated with increased odds of repeat infection. Syphilis elimination efforts should include messages about the risk for repeat infection and the importance of follow-up testing. Public health attention to individuals repeatedly infected with syphilis may help reduce local disease burdens. PMID- 22095365 TI - Using art to amplify youth voices on housing insecurity. PMID- 22095366 TI - The brain-to-brain loop concept for laboratory testing 40 years after its introduction. AB - Forty years ago, Lundberg introduced the concept of the brain-to-brain loop for laboratory testing. In this concept, in the brain of the physician caring for the patient, the first step involves the selection of laboratory tests and the final step is the transmission of the test result to the ordering physician. There are many intermediary steps, some of which are preanalytic, ie, before performance of the test; some are analytic and relate to the actual performance of the test; and others are postanalytic and involve transmission of test results into the medical record. The introduction of this concept led to a system to identify and classify errors associated with laboratory test performance. Errors have since been considered as preanalytic, analytic, and postanalytic. During the past 4 decades, changes in medical practice have significantly altered the brain-to-brain loop for laboratory testing. This review describes the changes and their implications for analysis of errors associated with laboratory testing. PMID- 22095367 TI - Critical values in the coagulation laboratory: results of a survey of the North American Specialized Coagulation Laboratory Association. AB - Critical values are vital to safe clinical and laboratory practice. To address the lack of information on critical values in coagulation, pattern-of-practice surveys were distributed to members of the North American Specialized Coagulation Laboratory Association. More than 70% of respondents had critical values for commonly performed tests. Median values were as follows: prothrombin time, more than 37 seconds; international normalized ratio, more than 5; activated partial thromboplastin time, more than 100 seconds; and fibrinogen level, less than 100 mg/dL. Critical value reporting generated a significant workload, with up to 15% of these tests yielding critical results. The median time to report critical values was 7 minutes for inpatients. Despite the lack of guidelines surrounding critical values in coagulation, this survey confirms that laboratories have reasonable and uniform practices. It also provides critical value medians and ranges for a wide range of tests. Laboratories without critical values or in the process of reviewing their values may find this survey of their peers useful. PMID- 22095368 TI - A well-designed online transfusion reaction reporting system improves the estimation of transfusion reaction incidence and quality of care in transfusion practice. AB - Recognizing and reporting a transfusion reaction is important in transfusion practice. However, the actual incidence of transfusion reactions is frequently underestimated. We designed an online transfusion reaction reporting system for nurses who take care of transfusion recipients. The common management before and after transfusion and the 18 most common transfusion reactions were itemized as tick boxes. We found the overall documented incidence of transfusion reaction increased dramatically, from 0.21% to 0.61% per unit of blood, after we started using an online reporting system. Overall, 94% (30/32) of nurses took only 1 week to become familiar with the new system, and 88% (28/32) considered the new system helpful in improving the quality of clinical transfusion care. By using an intranet connection, blood bank physicians can also identify patients who are having a reaction and provide appropriate recommendations immediately. A well designed online reporting system may improve the ability to estimate the incidence of transfusion reactions and the quality of transfusion care. PMID- 22095369 TI - Effect of telavancin (Vibativ) on routine coagulation test results. AB - Telavancin (Vibativ, Astellas Pharma US, Deerfield, IL) is a lipoglycopeptide antibiotic that has activity against gram-positive microorganisms, but also has the ability to bind to artificial phospholipids found in coagulation reagents. Normal pooled plasma was spiked with telavancin to obtain concentrations of 0, 12.5, 25, 50, 75, 100, 125, and 150 MUg/mL of drug. Samples were tested using 3 different prothrombin time/international normalized ratio (INR) and activated partial thromboplastin time (aPTT) reagent systems, as well as for fibrinogen level, thrombin time, D-dimer level, dilute Russell viper venom time (DRVVT), protein C activity, and protein S activity. There was no effect of telavancin seen with non-phospholipid-dependent assays: fibrinogen level, thrombin time, and D-dimer testing. All INR and aPTT systems demonstrated concentration-dependent increases in clotting times, with Innovin (Siemens Healthcare Diagnostics, Deerfield, IL) INRs the most dramatic. False-positive DRVVT ratios started at 12.5 MUg/mL of telavancin, with no effect on protein C or protein S levels until the telavancin level reached more than 100 MUg/mL. PMID- 22095370 TI - Pulmonary histologic changes in Marfan syndrome: a case series and literature review. AB - Marfan syndrome is one of the most common connective tissue diseases and may manifest with a range of symptoms and pathologic changes. We present a retrospective series of 5 cases of patients with Marfan syndrome and pulmonary pathology. Patients were young to middle-aged adults with absent or minimal smoking histories and absent to severe clinical pulmonary symptoms. Tissue specimens were obtained from the surgical pathology and autopsy services. Histologic examination revealed a consistent pattern of distal acinar emphysema in all patients. Comparisons are made with other cystic-type diseases of the lung that may histologically mimic this pattern. This is the largest contemporary series of histologic pulmonary involvement of Marfan syndrome and the first to describe this pattern of pulmonary changes in this patient population. PMID- 22095371 TI - Frequency of HER2 heterogeneity by fluorescence in situ hybridization according to CAP expert panel recommendations: time for a new look at how to report heterogeneity. AB - In 2009, a College of American Pathologists expert panel published supplemental HER2 testing recommendations suggesting that cases with between 5% and 50% individual cells amplified by fluorescence in situ hybridization be reported as "heterogeneous for HER2 gene amplification." We examined the implications of applying these recommendations to clinical practice in 1,329 consecutive breast cancer cases. By ratio criteria, 23.2% of cases met the proposed criteria for heterogeneity, of which 81.6% were not amplified and 15.5% were equivocal by standard criteria. In contrast, the proposed criteria based on HER2 signals per cell classified only 6.5% of cases as heterogeneous, of which only 8% (7/87) were not amplified and 79% (69/87) were equivocal by standard criteria. These results show that the 2 proposed criteria sets are not equivalent and that the ratio based definition results in large numbers of nonamplified cases being classified as heterogeneous. Further definition of optimal criteria with clinical relevance is needed before HER2 heterogeneity reporting is adopted in routine practice. PMID- 22095372 TI - The vanishing testis: a histomorphologic and clinical assessment. AB - Of patients with cryptorchidism, 5% have no palpable gonad. Physical examination or scrotal exploration demonstrates tissue nubbins or small nodules that constitute the vanishing testis syndrome. At the University of Chicago Hospitals (Chicago, IL; 2004-2008), 30 surgical pathology specimens from 29 patients with this clinical diagnosis underwent scrotal exploration. Histologic and immunohistochemical comparison was done with 7 fetal testes, 8 surgically removed nonneoplastic testes, and 2 cryptorchid testes. Routine histologic studies showed no seminiferous tubules in 18 cases (60%), fibrosis in all (100%), calcifications in 16 (53%), and hemosiderin deposits in 9 (30%). In 12 cases with seminiferous tubules (40%), there were Sertoli cells only. Scrotal exploration in such cases is clinically driven and results in the removal of any tissue present. Although published studies suggest the risk for future tumor development is low, possibly absent, the definitive removal of a testicle is established by an awareness of the histologic spectrum exhibited by testicular remnants. PMID- 22095373 TI - Different HER2 protein expression profiles aid in the histologic differential diagnosis between urothelial carcinoma in situ (CIS) and non-CIS conditions (dysplasia and reactive atypia) of the urinary bladder mucosa. AB - We evaluated HER2 expression profiles in 32 carcinoma in situ (CIS) and 31 non CIS conditions (5 dysplasia and 26 reactive atypia) of the urinary bladder mucosa by applying breast cancer scoring rules. In situ hybridization was performed on tissue microarrays to assess HER2 gene amplification status. Our immunoprofiling data disclosed moderate to strong HER2 expression in CIS, including the basal layer of the urothelium, and absent to weak HER2 expression in non-CIS conditions. From the histologic differential diagnostic standpoint, immunostaining for HER2 protein represents a useful adjunct to aid in the delineation between CIS and non-CIS conditions of the bladder mucosa. Pathogenically, aberrant HER2 protein expression in CIS seems to be more commonly associated with polysomy than with gene amplification. From a therapeutic viewpoint, prospective clinical studies should investigate the potential benefit of HER2-targeted therapies in CIS, particularly in cases unresponsive to conventional therapeutic regimens. PMID- 22095375 TI - Eliminating the "Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance" category from the Bethesda System for Reporting Thyroid Cytopathology. AB - The "Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS)" category in the Bethesda System for Reporting Thyroid Cytology is heterogeneous and includes both specimens with borderline cellularity/compromised quality and those with genuine atypia. We have used a reporting scheme that is similar to the Bethesda System but does not include an AUS/FLUS category. We retrospectively reviewed all reports on thyroid FNA and thyroidectomy specimens submitted to the Beth Israel Deaconess Medical Center from January 2006 to December 2008. The positive predictive values for various categories and subcategories in this scheme demonstrate that the AUS/FLUS category can be eliminated to provide information for the most appropriate management of patients with thyroid nodules. PMID- 22095374 TI - Lossless compression of JPEG2000 whole slide images is not required for diagnostic virtual microscopy. AB - The use of lossy compression in medical imaging is controversial, although it is inevitable to reduce large data amounts. In contrast with lossy compression, lossless compression does not impair image quality. In addition to our previous studies, we evaluated virtual 3-dimensional microscopy using JPEG2000 whole slide images of gastric biopsy specimens with or without Helicobacter pylori gastritis using lossless compression (1:1) or lossy compression with different compression levels: 5:1, 10:1, and 20:1. The virtual slides were diagnosed in a blinded manner by 3 pathologists using the updated Sydney classification. The results showed no significant differences in the diagnosis of H pylori between the different levels of compression in virtual microscopy. We assume that lossless compression is not required for diagnostic virtual microscopy. The limits of lossy compression in virtual microscopy without a loss of diagnostic quality still need to be determined. Analogous to the processes in radiology, recommendations for the use of lossy compression in diagnostic virtual microscopy have to be worked out by pathology societies. PMID- 22095376 TI - Susac syndrome: an organ-specific autoimmune endotheliopathy syndrome associated with anti-endothelial cell antibodies. AB - Susac syndrome (SS) is the triad of encephalopathy, branch retinal artery occlusions (BRAOs), and hearing loss. Migraines may herald and accompany encephalopathy. Little is known about pathogenesis. Based on light microscopic findings in brain biopsy material analogous to anti-endothelial cell antibody (AECA)-mediated microvascular injury, we postulated that SS microangiopathy was attributable to AECAs. We examined serum samples from 11 patients with SS for AECAs; 9 were positive by indirect immunofluorescence and Western blot studies. A highly distinctive band on Western blots corresponding to a 50-kDa protein was observed in 8 positive SS samples; the other positive case exhibited specific reactivity with a protein band at 40 kDa. Of the 2 negative cases, 1 had been inactive since 1988; the other was an abortive variant characterized solely by BRAOs. There was enhanced surface binding of SS serum using live endothelial cell substrates compared with samples from healthy subjects. Additional serum samples from apparently healthy patients, 2 with atypical migraines, and patients with other forms of autoinflammatory disease did not show the distinctive band of immunoreactivity. SS is a distinct autoimmune endotheliopathy syndrome associated with AECAs; the antibody target seems specific in many cases and may be a disease biomarker. The exact role of AECAs in disease propagation remains unanswered. PMID- 22095377 TI - A new PCR-based mass spectrometry system for high-risk HPV, part I: methods. AB - Infection with high-risk (HR) human papillomaviruses (HPVs) has been confirmed as the necessary cause of cervical cancer. There are many studies that have established and confirmed the relationship of specific HPV types and the risk of invasive cervical cancer. We have developed a novel genotyping method for detecting 14 HR-HPV genotypes simultaneously with MassARRAY (Sequenom, San Diego, CA) technique based on the matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF) mass spectrometry (MS). All 14 HPVs showed high specificities and high sensitivities in the plasmid test; lower detection limits for each genotype were from 10 to 100 copies. Furthermore, the MS system has high throughput capacities, capable of processing, with type-specific output, 4,500 samples in 24 hours. The MS HPV assay is a sensitive and useful tool for HPV genotyping. It has the potential to be suitable for large-scale epidemiologic studies and routine diagnostic clinical applications owing to its high-throughput capacity, high sensitivity, and low cost per case. PMID- 22095378 TI - A new PCR-based mass spectrometry system for high-risk HPV, part II: clinical trial. AB - This was a population-based clinical trial of a polymerase chain reaction-based multiplex high-risk human papillomavirus (HR-HPV) assay using mass spectrometry (MassARRAY [Sequenom, San Diego, CA] matrix-assisted laser desorption/ionization time-of-flight mass spectrometry system [MALDI-TOF]). Participants were 10,000 women between the ages of 25 and 59 years in Guangdong Province, China (SHENCCAST II Study). All women collected a self-sample (tested with Cervista [Hologic, Marlborough, MA] and MALDI-TOF) followed by a clinician-collected cervical sample (for cytology, Hybrid Capture 2 [HC2; Qiagen, Gaithersburg, MD], Cervista, and MALDI-TOF). Patients with any abnormal result were asked to return for colposcopy and biopsies. This analysis included the data for 8,556 women. The sensitivity values for cervical intraepithelial neoplasia (CIN) 3 or worse for a direct cervical sample were 97.9%, 95.1%, and 94.3 for HC2, Cervista, and MALDI-TOF, respectively (P > .05). The sensitivity for CIN 3 or worse for a self-collected sample tested with MALDI-TOF was also 94.3%, which was similar to a clinician obtained endocervical sample assayed with the 3 HR-HPV assays. MALDI-TOF combined with a self-collected sample provides a highly sensitive, high-throughput, low cost-per-case assay for mass screening. PMID- 22095379 TI - Clinical verification of the performance of the pathwork tissue of origin test: utility and limitations. AB - Gene expression-based assays have been introduced into the clinical arena to assist in the diagnosis of poorly differentiated or undifferentiated tumors. The US Food and Drug Administration has cleared the microarray-based Pathwork Tissue of Origin (TOO) Test (Pathwork Diagnostics, Sunnyvale, CA) for the molecular characterization of such challenging specimens. We aimed at verifying the analytic and clinical performance of this test on 43 poorly differentiated and undifferentiated tumor samples, including 6 off-panel cases and 7 cancers of unknown primary (CUP). Our results showed 97% (95% confidence interval, 80.4% 99.8%) agreement between the Pathwork TOO Test result and the complete diagnosis, which included clinical correlations and immunohistochemical staining, after the original diagnosis. We concluded that for off-panel and CUP samples, the tissue type and the cell type may be confounded by the Pathwork TOO Test and that careful clinicopathologic assessment is needed when interpreting results from this helpful ancillary tool for pathologists. PMID- 22095380 TI - Comparison of immunocytochemical sensitivity between formalin-fixed and alcohol fixed specimens reveals the diagnostic value of alcohol-fixed cytocentrifuged preparations in malignant effusion cytology. AB - The most commonly used fixative in effusion cytology is formalin. In the present study, the immunocytochemical properties of formalin-fixed and alcohol-fixed specimens were compared to evaluate the usefulness of alcohol-fixed cytocentrifuged preparations for routine cytologic diagnosis. A total of 269 effusion samples and 17 primary antibodies were used. The sensitivity of immunocytochemical studies in alcohol-fixed specimens was similar and correlated to that of formalin-fixed specimens, suggesting that alcohol-fixed cytocentrifuged preparations are useful in effusion cytology. Pretreatment with or without heat-induced antigen retrieval revealed that antigen retrieval was unnecessary for immunocytochemical studies with most primary antibodies in alcohol-fixed cytocentrifuged preparations. The present study describes the use of immunocytochemical studies with alcohol-fixed cytocentrifuged preparations for diagnosis in routine effusion cytology. PMID- 22095381 TI - Simplified flow cytometric assessment in mycosis fungoides and Sezary syndrome. AB - By using flow cytometry with markers for CD3, CD4, CD26, and CD7, we examined the blood samples of 109 patients for abnormal T cells: 69 patients with mycosis fungoides (MF)/Sezary syndrome (SS), 31 hospitalized control subjects, and 9 patients with inflammatory skin disease. T cells were identified as quantitatively abnormal (>15% CD26- or CD7- T cells) or phenotypically abnormal (CD26- or CD7- T cells with bright or dim CD3 or CD4 or bright CD7). Patients were followed for a median of 82 months, and abnormal T cells were correlated with diagnosis, clinical outcome, and other laboratory parameters. Abnormal T cell populations were identified in 46% of patients with MF/SS (32/69) and correlated with disease extent. Quantitative abnormalities were more frequent than phenotypic abnormalities, and CD4+/CD26- T cells were more frequent than CD4+/CD7- T cells. CD26- T cells correlated better with disease extent than did CD7 -. Increasing numbers of abnormal T cells were associated with worsening disease. Flow cytometry provides valuable information for diagnosis, prognosis, and therapeutic efficacy in MF/SS. PMID- 22095382 TI - Flow cytometric analysis of surface light chain expression patterns in B-cell lymphomas using monoclonal and polyclonal antibodies. AB - Light chain (LC) expression by flow cytometry (FC) in B cell non-Hodgkin lymphomas (B-NHLs) can occasionally be detected with one anti-LC antibody but not with another. We retrospectively analyzed 564 four-color FC files from B-NHLs, assessing LC staining with monoclonal antibodies (mAbs) and polyclonal antibodies (pAbs). Discrepancies in LC expression between mAbs and pAbs were present in 9.2% of cases, mainly in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 11.1%), diffuse large B-cell lymphoma (DLBCL; 10.2%), follicular lymphoma (9.5%), and mantle cell lymphoma (11.1%) and most frequently in body fluids. Equal proportions of cases were LC+ only with pAbs (4.8%) or mAbs (4.4%). Negative LC expression with both antibodies was present in 7.5% of cases, most frequently in DLBCL (21.6%) and body fluids (27.6%). Evaluation with both mAbs and pAbs increases the sensitivity for LC detection, with no single reagent outperforming the other, although CLL/SLL preferentially showed LC expression with pAbs. PMID- 22095383 TI - Multiparametric flow cytometry for identification and fluorescence activated cell sorting of five distinct B-cell subpopulations in normal tonsil tissue. AB - The purpose of this study was to establish a procedure capable of isolating distinct B-cell subpopulations from human tonsils as a basis for subsequent molecular analyses. Overall, 5 distinct B-cell subpopulations were purified from fresh tonsils based on their fluorescence surface marker expression: naive B cells, centroblasts, centrocytes, memory B cells, and plasmablasts. The immunophenotypic identity of the subpopulations was verified by quantitative real time reverse transcriptase-polymerase chain reaction using the proliferation marker MKI-67 and 6 B-cell-associated differentiation markers (BACH2, BCL6, PAX5, IRF4, PRDM1, and XBP1). Furthermore, within the centroblast compartment, large and small centroblasts could be distinguished and large centroblasts were shown to proliferate with a morphologic appearance of a "centroblast"-like cell but with lower gene expression of the germinal center markers BCL6 and BACH2 vs small centroblasts. This study has established a detailed and fast procedure for simultaneous sorting of up to 5 distinct maturation-associated B-cell subpopulations from human tonsils. PMID- 22095384 TI - Accounting for artifactually elevated HbA2 in cases of Hb hope when measured by capillary electrophoresis. PMID- 22095385 TI - Macrophage metalloelastase (MME) as adjuvant for intra-tumoral injection of oncolytic adenovirus and its influence on metastases development. AB - Oncolytic adenoviruses are a promising treatment alternative for many advanced cancers, including colorectal cancer. However, clinical trials have demonstrated that single-agent therapy in advanced tumor masses is rarely curative. Poor spreading of the virus through tumor tissue is one of the major issues limiting efficacy. As oncolytic viruses kill preferentially cancer cells, high extracellular matrix (ECM) content constitutes potential barriers for viral penetration within tumors. In this study, the ECM-degrading proteases relaxin, hyaluronidase, elastase and macrophage metalloelastase (MME) were tested for their antitumor efficacy alone and in combination with oncolytic adenovirus. MME improved the overall antitumor efficacy of oncolytic adenovirus in subcutaneous HCT116 xenografts. In a liver metastatic colorectal cancer model, intra-tumoral treatment of primary tumors from HT29 cells with MME monotherapy or with oncolytic adenovirus inhibited tumor growth. Combination therapy showed no increased mortality in comparison with either monotherapy alone. Contradictory results of effects of MME on tumorigenesis and metastasis formation have been reported in the literature. This study demonstrates for the first time in a metastatic animal model that MME, as a monotherapy or in combination with oncolytic virus, does not increase tumor invasiveness. Co-administration of MME and oncolytic adenovirus may be a suitable approach for further optimization aiming at clinical applications for metastatic colorectal cancer. PMID- 22095386 TI - Sonoporation-mediated anti-angiogenic gene transfer into muscle effectively regresses distant orthotopic tumors. AB - Ultrasound (US) is an effective tool for local delivery of genes into target tumors or organs. In combination with microbubbles, US can temporarily change the permeability of cell membranes by cavitation and facilitate entry of plasmid DNA into cells. Here, we demonstrate that repeated US-mediated delivery of anti angiogenic genes, endostatin or calreticulin, into muscle significantly inhibits the growth of orthotopic tumors in the liver, brain or lung. US-mediated anti angiogenic gene therapy also seems to function as an adjuvant therapy that significantly enhances the antitumor effects of the chemotherapeutic drug doxorubicin and adenovirus-mediated cytokine gene therapy. Significantly higher levels of tumor apoptosis or tumor-infiltrating lymphocytes were observed after combined therapy consisting of either anti-angiogenic therapy and chemotherapy, or anti-angiogenic therapy and immunotherapy. Taken together, our experiments demonstrate that intramuscular delivery of anti-angiogenic genes by US exposure can effectively treat distant orthotopic tumors, and thus has great therapeutic potential in terms of clinical treatment. PMID- 22095387 TI - Human papillomavirus in vaginal intraepithelial neoplasia. AB - There are limited data on the prevalence and distribution of human papillomavirus (HPV) genotypes in vaginal intraepithelial neoplasia (VAIN). We sought to clarify this issue in a series of 450 VAIN cases with a confirmed diagnosis between 1990 and 2006. HPV genotyping was performed using paraffin-embedded specimens and polymerase chain reaction (PCR)-based methods. Multiple HPV types were validated by E6 type-specific PCR and direct sequencing. The HPV genotypes of the vaginal and cervical neoplasms were compared for those with incident VAIN and a history of previous/concomitant cervical neoplasms. Ki-67 was performed for supporting diagnosis of VAIN. Of these 450 VAIN cases (median age, 59 years; range, 19-93), two with missing paraffin blocks and 54 with poor DNA quality were excluded. HPV was detected in 273/394 (69.3%) VAIN, and multiple infections were found in 17.9% of HPV-positive samples. The leading types were HPV16 (35.5%), HPV58 (9.9%), HPV52 (9.9%), HPV39 (8.4%), HPV33 (7.3%) and HPV53 (7.0%). Among the 156 cases with a history of previous cervical neoplasia, 29.0% had concordant HPV genotypes, while synchronous VAIN samples (n = 49) were more likely to harbor concordant genotypes (58.7%) with the concomitant cervical neoplasm (p = 0.0003). Whether those HPV types in the incident VAIN lesions had existed in the vaginal epithelium at the time of the previous cervical neoplasia or a new acquisition needs to be clarified in prospective follow-up studies. PMID- 22095388 TI - The expression and pharmacological characterization of nicotinic acetylcholine receptor subunits in HBE16 airway epithelial cells. AB - This study characterizes the expression and the biological effects of the nicotinic acetylcholine receptor (nAChR) on human airway epithelial cells. Cultured HBE16 airway epithelial cells were incubated with either nicotine or cigarette smoke extract (CSE). The nAChR gene and protein expression in cells were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), real time PCR, and western blot. The protein expression of the nAChR subunits, alpha1, alpha5, and alpha7, were evaluated by immunohistochemistry. Cells were subsequently transfected with alpha1-, alpha5-, and alpha7-specific siRNAs, and the effects of nicotine on the production of the pro-inflammatory factors, TNF alpha, IL-8, and IL-6 in transfected cells were analyzed using an enzyme-linked immunosorbent assay and real-time PCR. We detected alpha1, alpha5, alpha7, and beta2 subunits in untreated HBE16 cells, and their expression was elevated after nicotinic incubation. Importantly, the most significant increase in expression was observed in the alpha5 and alpha7 subunits. However, CSE did not cause a significant enhancement in the expression of these genes and proteins. Cells pretreated with nicotine prior to lipopolysaccharide (LPS) stimulation exhibited a lower production of TNF-alpha, IL-8, and IL-6 compared to LPS-treated (only) cells. Cells that were transfected with alpha7 siRNA and subsequently incubated with nicotine and LPS, exhibited a higher expression of TNF-alpha, IL-8, and IL-6 compared with non-transfected cells or alpha1 and alpha5 siRNA-transfected cells. In alpha1- and alpha5-siRNA-transfected cells, the expression of TNF-alpha, IL-8, and IL-6 showed no significant difference compared with non-transfected cells. Therefore, we concluded that alpha1, alpha5, alpha7, and beta2 nAChR subunits are highly expressed in human bronchial epithelial cells (HBE16) after nicotinic incubation and that the alpha7 subunit is involved in the nicotine-induced inhibitory effect on the production of inflammatory factors. Moreover, alpha1, alpha5, and beta2 subunits did not play an important role in this process. PMID- 22095389 TI - Characterization of Escherichia coli [NiFe]-hydrogenase distribution during fermentative growth at different pHs. AB - The contribution made by each of the three active [NiFe]-hydrogenases (Hyd) of Escherichia coli during fermentation of glucose or glycerol in peptone-based medium at different pHs was analysed. The activities of the hydrogen-oxidizing Hyd-1 and Hyd-2 enzymes showed a reciprocal dependence on the pH of the medium while Hyd-3, a key component of the hydrogen-evolving formate hydrogenlyase complex, was mainly active at pH 6.5. Our findings identify the conditions during fermentation of glucose or glycerol under which each [NiFe]-hydrogenase is optimally active and demonstrate a previously unrecognized dependence on Hyd-1 activity at low pH. PMID- 22095390 TI - The effects of garlic-derived sulfur compounds on cell proliferation, caspase 3 activity, thiol levels and anaerobic sulfur metabolism in human hepatoblastoma HepG2 cells. AB - The aim of the present studies was to determine whether the mechanism of biological action of garlic-derived sulfur compounds in human hepatoma (HepG2) cells can be dependent on the presence of labile sulfane sulfur in their molecules. We investigated the effect of allyl sulfides from garlic: monosulfide, disulfide and trisulfide on cell proliferation and viability, caspase 3 activity and hydrogen peroxide (H(2)O(2)) production in HepG2 cells. In parallel, we also examined the influence of the previously mentioned compounds on the levels of thiols, glutathione, cysteine and cysteinyl-glycine, and on the level of sulfane sulfur and the activity of its metabolic enzymes: rhodanese, 3-mercaptopyruvate sulfurtransferase and cystathionase. Among the compounds under study, diallyl trisulfide (DATS), a sulfane sulfur-containing compound, showed the highest biological activity in HepG2 cells. This compound increased the H(2)O(2) formation, lowered the thiol level and produced the strongest inhibition of cell proliferation and the greatest induction of caspase 3 activity in HepG2 cells. DATS did not affect the activity of sulfurtransferases and lowered sulfane sulfur level in HepG2 cells. It appears that sulfane sulfur containing DATS can be bioreduced in cancer cells to hydroperthiol that leads to H(2)O(2) generation, thereby influencing transmission of signals regulating cell proliferation and apoptosis. PMID- 22095391 TI - Ultrasound-guided closed muscle biopsy: a useful tool for rheumatologists : case report: recurrent focal myositis of the gastrocnemius muscle. PMID- 22095392 TI - Vertebral osteomyelitis: eight years' experience of 100 cases. AB - To evaluate the etiology and characteristics of vertebral osteomyelitis cases in our country, patients with vertebral osteomyelitis between January 2000 and December 2007 were included in this study. Clinical and laboratory data of the patients were collected from the medical records retrospectively. Of these 100 patients, 44 had pyogenic, 24 had brucellar, and 32 had tuberculous spondylodiscitis. The age of the patients ranged from 13 to 82 years, with a mean of (SD+/-) 55 +/- 15.6 years. Within the pyogenic group, 10 (22.7%) patients had a spinal surgery history, and in 18 patients of the pyogenic group, an etiological agent was isolated. Ten (56%) of these 18 were methicillin-sensitive Staphylococcus aureus. While all of the patients included in this study suffered from pain, 49 of these had fever. Sixty-nine percent of the patients had lumbar involvement. The etiological distribution may differ according to geographical areas. Although brucella and tuberculosis (TB) are endemic in our country, pyogenic vertebral osteomyelitis was more frequent. The most common involved area in our patients was the lumbar vertebrae. Although thoracic involvement may be more predominant in tuberculous vertebral osteomyelitis, it does not strongly suggest TB. Magnetic resonance imaging may exclude some disorders mimicking vertebral osteomyelitis and may delineate the degree of the involvement. Microbiological and/or histopathological examination of computerized tomography guided fine-needle aspiration biopsies are the mainstays for the diagnosis. Suspicion and early diagnosis seem critical for preventing sequelae development. PMID- 22095393 TI - Detection of latent tuberculosis infection in rheumatologic diseases before anti TNFalpha therapy: tuberculin skin test versus IFN-gamma assay. AB - We aimed to evaluate tuberculin skin test (TST) and interferon-gamma (IFN-gamma) test results for latent tuberculosis infection (LTBI) in patients with rheumatologic diseases prior to anti-TNFalpha therapy. Ninety patients were evaluated in the study at the Departments of Chest Diseases and Rheumatology for anti-TNFalpha therapy for their rheumatologic diseases. Tuberculin skin test was performed (Mantoux method) and peripheral blood samples were collected for IFN gamma assay (QuantiFeron TB-Gold In Tube) before the anti-TNFalpha therapy. Of 90 patients, TST positivity was detected in 56 (62.2%) patients, while IFN-gamma positivity was detected in 34 (37.8%) patients. Among 56 TST positive patients, IFN-gamma positivity was detected in 24 (42.9%) patients, and among 34 TST negative patients, IFN-gamma positivity was detected in 10 (29.4%) patients. There was no significant agreement between TST and IFN-gamma assay results (Kappa = 0.12, P = 0.2). Forty-three (47.8%) patients were using immunosuppressive drugs owing to their rheumatologic diseases. In this group, TST and IFN-gamma positivity is significantly lower than in those who did not receive immunosuppressive treatment (P < 0.05). We conclude that the IFN-gamma assay may not be preferred to TST as a diagnostic test in patients with rheumatologic diseases prior to anti-TNFalpha treatment. PMID- 22095394 TI - Recurrent uveitis due to sildenafil usage in a patient with Behcet's disease. AB - Behcet's disease (BD) may cause uveitis and retinal vasculitis in nearly half of the patients. Uveitis is one of the most serious complications that can lead to blindness. Sildenafil (Viagra(R)) and the other phosphodiesterase type 5 (PDE5) inhibitors are the first-line options for the treatment of erectile dysfunction, but transient visual symptoms and serious ocular side effects have been reported in PDE5 inhibitor users. Herein, we report a case with BD who applied to our outpatient unit with recurrent uveitis after sildenafil therapy. PMID- 22095395 TI - Relationship between body mass index, fat mass and lean mass with SF-36 quality of life scores in a group of fibromyalgia patients. AB - Patients suffering from fibromyalgia (FM) had widespread musculoskeletal pain and stiffness, fatigue, sleep disorders, cognitive impairment and other symptoms, which seriously affects their quality of life (QoL), making it difficult to perform normal activities. Moreover, FM has been associated with a higher prevalence of overweight and obesity than in the general population. Weight reduction has been beneficial in both FM and other rheumatic patients. Obesity and overweight have been pointed as playing a relevant role in FM symptoms; however, it is necessary to find out more about this relationship. The objective of this study was to evaluate the relationship between body mass index (BMI), fat mass (fM) and lean mass (lM) with quality of life in a group of FM patients. 103 women, with a mean age of 53.74 +/- 7.81, and members of different FM patient associations from Spain participated in our study. Some anthropometric measures were taken like weight, height, BMI, body fat mass and lean mass. FM patients QoL was assessed by the Short-Form Health Survey, SF-36 questionnaire. Statistical reports were based on mean, standard deviation and correlation, but significance was tested by nonparametric methods. BMI, fM and lM correlated differently with the specific SF-36 scores. BMI had a high negative correlation with emotional role, fM with bodily pain and lM almost with all scores but specially with emotional role, vitality and physical role. The outcome of this study reveals some interesting relationships, which need to be further investigated to improve the management of FM patients. PMID- 22095396 TI - Do true preretinal (subhyaloid) hemorrhages occur in infants? PMID- 22095397 TI - Dry powder inhaler device influence on carrier particle performance. AB - Dry powder inhalers (DPIs) are distinguished from one another by their unique device geometries, reflecting their distinct drug detachment mechanisms, which can be broadly classified into either aerodynamic or mechanical-based detachment forces. Accordingly, powder particles experience different aerodynamic and mechanical forces depending on the inhaler. However, the influence of carrier particle physical properties on the performance of DPIs with different dispersion mechanisms remains largely unexplored. Carrier particle trajectories through two commercial DPIs were modeled with computational fluid dynamics (CFD) and the results were compared with in vitro aerosol studies to assess the role of carrier particle size and shape on inhaler performance. Two percent (w/w) binary blends of budesonide with anhydrous and granulated lactose carriers ranging up to 300 MUm were dispersed from both an Aerolizer(r) and Handihaler(r) through a cascade impactor at 60 L min(-1). For the simulations, carrier particles were modeled as spherical monodisperse populations with small (32 MUm), medium (108 MUm), and large (275 MUm) particle diameters. CFD simulations revealed the average number of carrier particle-inhaler collisions increased with carrier particle size (2.3 4.0) in the Aerolizer(r), reflecting the improved performance observed in vitro. Collisions within the Handihaler(r), in contrast, were less frequent and generally independent of carrier particle size. The results demonstrate that the aerodynamic behavior of carrier particles varies markedly with both their physical properties and the inhalation device, significantly influencing the performance of a dry powder inhaler formulation. PMID- 22095399 TI - The SuBliMinaL Toolbox: automating steps in the reconstruction of metabolic networks. AB - The generation and use of metabolic network reconstructions has increased over recent years. The development of such reconstructions has typically involved a time-consuming, manual process. Recent work has shown that steps undertaken in reconstructing such metabolic networks are amenable to automation. The SuBliMinaL Toolbox (http://www.mcisb.org/subliminal/) facilitates the reconstruction process by providing a number of independent modules to perform common tasks, such as generating draft reconstructions, determining metabolite protonation state, mass and charge balancing reactions, suggesting intracellular compartmentalisation, adding transport reactions and a biomass function, and formatting the reconstruction to be used in third-party analysis packages. The individual modules manipulate reconstructions encoded in Systems Biology Markup Language (SBML), and can be chained to generate a reconstruction pipeline, or used individually during a manual curation process. This work describes the individual modules themselves, and a study in which the modules were used to develop a metabolic reconstruction of Saccharomyces cerevisiae from the existing data resources KEGG and MetaCyc. The automatically generated reconstruction is analysed for blocked reactions, and suggestions for future improvements to the toolbox are discussed. PMID- 22095398 TI - Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128). AB - Mericitabine (RG7128) is a nucleoside polymerase inhibitor (NPI), which requires intracellular uptake and phosphorylation to two active triphosphates. Mathematical modeling has provided important insights for characterizing hepatitis C virus (HCV) RNA decline and estimating in vivo effectiveness of antiviral agents; however, it has not been used to characterize viral kinetics with NPIs. HCV RNA was frequently measured in 32 treatment-experienced patients infected with HCV genotype 1 during and after mericitabine monotherapy for 14 days with 750 mg or 1500 mg administered once (qd) or twice daily (bid). The initial decline of HCV RNA was typically slower than with interferon-alpha or protease inhibitors, and 12 patients presented a novel pattern of HCV RNA kinetics characterized by a monophasic viral decline. Viral kinetics could be well fitted by assuming that the effectiveness in blocking viral production gradually increased over time to reach its final value, epsilon(2), consistent with previous accumulation time estimates of intracellular triphosphates. epsilon(2) was high with bid dosing (mean 750 mg and 1500 mg: 98.0% and 99.8%, respectively; P = 0.018) and significantly higher than in patients treated qd (mean qd versus bid: 90% versus 99%, P < 10(-7)). Virus rebounded rapidly upon drug discontinuation, which was attributed to the elimination of active drug and the subsequent decline of drug effectiveness, with mean t(1/2) = 13.9 hours in the bid regimens. CONCLUSION: The observed slower initial decline likely represents the time needed to accumulate intracellular triphosphates and is consistent with in vitro data. When administered bid, mericitabine reached a high, dose-dependent, final effectiveness in blocking viral production that rapidly dropped upon treatment cessation. Understanding HCV RNA kinetics with mericitabine could provide valuable insights for combining it with other direct acting antiviral agents. PMID- 22095400 TI - The attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to collagen and fibronectin. AB - This study investigated the attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to the extracellular matrix. Five New Zealand White rabbit forepaws were dissected to isolate the flexor tendon core, tendon surface and synovial sheath, which were explanted separately. A further 10 animals were subjected to flexor tendon injuries, randomized to either mobilization or immobilization, and adhesions were explanted at 2 weeks. Cell groups were tested for attachment to collagen type-I or fibronectin and morphometric analysis was made. The attachment of intrinsic tendon cells and adhesion cells from mobilized tendons to both matrix proteins was statistically significantly greater than that of extrinsic tendon cells and adhesion cells from immobilized tendons. Adhesion cells from mobilized tendons were statistically significantly more elongated, which may correlate with the deposition of a more organized matrix. Because the synovial sheath cells were least attached to matrix proteins, selective treatments that reduce cell attachment may be used to exclude them, without inhibiting intrinsic tendon healing. PMID- 22095401 TI - Avascular osteonecrosis of the scaphoid (Preiser's disease) in a 13-year-old boy treated with vascularized bone graft. PMID- 22095402 TI - Wrist extension strength required for power grip: a study using a radial nerve block model. AB - The aim of this study was to investigate the correlation of wrist extension strength (WES) and grip strength (GS) using a radial nerve block, and to determine the WES required to prevent the "wrist flexion phenomenon" (antagonistic WES) when making a fist. We tested 14 arms in seven healthy males. WES and GS were measured before blocking as standard WES and standard GS. All participants then had radial nerve blocks with mepivacaine hydrochloride. During the recovery process from radial nerve blockade, WES and GS were recorded every 5 minutes. There was a very strong correlation between WES and GS (p < 0.0001). The mean antagonistic WES was 51% of standard WES, and the mean GS, recorded at the same time, was 66% of standard GS. PMID- 22095403 TI - In de Quervain's with a separate EPB compartment, ultrasound-guided steroid injection is more effective than a clinical injection technique: a prospective open-label study. AB - We compared ultrasonography (US)-guided injection, targeting the extensor pollicis brevis (EPB) in de Quervain's disease (dQD) with septation, to clinical injection. Forty-four wrists were randomly allocated to US-guided or manual (non US-guided) injection. At 4 weeks, pain was significantly reduced in both groups. Pain on the 100 mm visual analogue scale (VAS) for the US group was 80.3 (SD 19.6) mm at baseline and 25.6 (SD 15.1) mm at 4 weeks after injection (p = 0.004). Values for the manual group were 78.0 (SD 18.5) mm at baseline and 58.2 (SD 21.9) mm at 4 weeks after injection (p = 0.04). Pain on the VAS showed a more significant decrease in the US-guided than in the manual injection group (p = 0.0007) from baseline to 4 weeks after injection. The results of this study suggest US-guided injection targeting the EPB in dQD patients with septation is more effective than manual injection. PMID- 22095405 TI - Morphea associated with the use of adalimumab: a case report and review of the literature. AB - Therapy with TNF blockers may induce cutaneous adverse events, but the development of morphea, a localized scleroderma lesion, is extremely infrequent. We describe a 37-year-old man with ankylosing spondylitis treated with adalimumab who developed morphea lesions in the lower limbs after 12 months of treatment. Adalimumab was discontinued, which resulted in progressive improvement in the skin lesions, with only mild hyperpigmentation remaining. We also review reports of morphea and other adverse cutaneous events related to anti-TNF treatment. PMID- 22095406 TI - Extraction of lignins from aqueous-ionic liquid mixtures by organic solvents. AB - The commercial development of ionic liquids (ILs) to pretreat lignocellulose by dissolution of whole biomass and cellulose precipitation by addition of water is hindered by the absence of an effective technique to recover the lignin content of the biomass from the IL. Three organic solvents [ethyl acetate, 1,4-dioxane, and tetrahydrofuran (THF)] were studied for their ability to form a two-liquid phase system with water and 1-ethyl-3-methylimidazolium acetate ([C(2)mim][OAc]), and for partitioning model lignins and lignin monomers between the two liquid phases. Ternary diagrams were obtained for three [C(2)mim][OAc]/organic solvent/water systems at 22 degrees C. Partition coefficients were measured for several types of lignin in these three systems. Partition coefficients increase with rising water content in the IL phase, and depend strongly on the type of lignin and on the organic solvent. Partition coefficients rise as the pH of the ionic-liquid-rich phase falls. Small molecule model lignin monomer compounds (guaiacol, syringaldehyde) are also readily extracted from the IL/water system by THF. PMID- 22095404 TI - ER stress, p66shc, and p-Akt/Akt mediate adjuvant-induced inflammation, which is blunted by argirein, a supermolecule and rhein in rats. AB - We investigated the anti-inflammatory activities of argirein and rhein on inflammatory edema in rat paw which was caused by complete adjuvant, compared with ibuprofen. We hypothesized that the adjuvant-induced inflammation is attributed to upregulation of activating transcript factor 6 (ATF6; a chaperone for endoplasmic reticulum (ER) stress), p66Shc (an adaptive protein modulating oxidative stress), and NADPH oxidase subunits p22phox and gp91phox in the inflamed tissues. Biomarkers were measured in the rat paw in association with monitoring swellings. The primary inflammatory edema of the injected paw occurred rapidly and sustained over a couple of days, and the secondary inflammation developed 2 weeks later. The inflammatory edema was accompanied by upregulation of cytokines including ATF6, p66Shc, p22phox, gp91phox, and MMP-2 and an increase in ratio of p-Akt/Akt in the afflicted paw. These were suppressed by either argirein and rhein or ibuprofen. These findings indicate that ER stress, upregulated p66Shc, and phosphorylated Akt are actively implicated in the inflammatory zone caused by adjuvant injection. These biomarkers were causal factors responsible for inflammation of the afflicted paw and were suppressed by a supermolecule argirein and rhein, and the anti-inflammatory activities of the two compounds were comparable to that of ibuprofen. PMID- 22095407 TI - Click synthesis of ubiquitin dimer analogs to interrogate linkage-specific UBA domain binding. AB - A new route to the synthesis of triazole-linked ubiquitin dimers (diUbs) as structural analogs of the seven diUbs is reported. Binding studies with the Lys48 specific UBA domain of the Mud1 protein suggest that they represent functionally suitable surrogates of their native counterparts linked by an isopeptide bond. PMID- 22095408 TI - Effects of pesticide formulations and active ingredients on the coelenterate Hydra attenuata (Pallas, 1766). AB - Lethal effects of active ingredients and formulations of widely used soybean pesticides were assessed with the Hydra attenuata toxicity test. Studied pesticides were insecticides chlorpyrifos and cypermethrin, and herbicide glyphosate. Results indicate the following toxicity trend: chlorpyrifos > cypermethrin > glyphosate. Tested active ingredients of insecticides and respective formulations did not significantly differ between them. Glyphosate formulation exhibited higher toxicity at low concentrations (LC(1-10)) respect to active ingredient, reversing this behavior at higher concentrations (LC(50-90)). Comparing H. attenuata sensitivity with existent toxicity data for aquatic organisms indicates that this species is poorly sensitive to tested insecticides and highly sensitive to the herbicide. PMID- 22095409 TI - Interrater reliability of endoscopic parameters following sinus surgery. AB - OBJECTIVES/HYPOTHESIS: To determine the interrater reliability of a set of postoperative endoscopic scoring parameters in patients with chronic rhinosinusitis who have undergone endoscopic sinus surgery (ESS). STUDY DESIGN: Prospective cohort with retrospective review. METHODS: One hundred twenty video endoscopic evaluations in 20 subjects recorded at 14, 30, and 45 days after ESS were scored in real time by the clinical investigators who performed the endoscopies and recorded the videos and retrospectively by an independent panel of four sinus surgeons who were blinded to all information. The scoring parameters included categoric grading for adhesion formation and middle turbinate position and continuous grading (visual analog scale) for degree of inflammation and crusting. Interrater reliability of the panel members was assessed using the Fleiss kappa test, bias index and prevalence index for categoric data, and the Shrout-Fleiss test for continuous data. The level of agreement between the panel and the real-time clinical investigator was also assessed. RESULTS: For categoric variables, strong agreement between raters on the panel was found for both middle turbinate position (kappa=0.499, prevalence index=0.925) and adhesions (kappa=0.364, prevalence index=0.829). For continuous data, good agreement between raters was found for both inflammation (reliability coefficient=0.554) and crusting (reliability coefficient=0.620). Real-time investigator scoring and panel scoring showed strong agreement. CONCLUSIONS: These results suggest that the endoscopic scoring parameters assessed (middle turbinate position, adhesions, inflammation, and crusting) have acceptable interexaminer reproducibility and are suitable for evaluating ESS outcomes in the postsurgical period. PMID- 22095410 TI - [Non-operative treatment for severe forms of infantile idiopathic scoliosis]. AB - INTRODUCTION: Infantile idiopathic scoliosis (IIS) is a rare orthopaedic condition. Braces and casts are popular options in the treatment of IIS but there is a paucity of studies commenting on the outcome of non-operative treatment. The purpose of this study was to analyse failure and success after non-operative treatment for severe forms of IIS. METHODS: We retrospectively reviewed the data of all children who had been treated for IIS between 2003 and 2009 at a single institution. After calculating the failure and success rates, we additionally performed a risk factor analysis for patients who failed non-operative treatment. Chi (2) and T tests were used for statistical analysis with significance set at p < 0.05. RESULTS: 25 children with an average age of 11 months and an Cobb angle of 46 degrees at presentation were analysed. Seven (28 %) patients were considered as having failed non-operative treatment after an average follow-up of 28 months. The pretreatment Cobb angle was identified as single significant risk factor for failure (55 versus 42) while neither age, gender, nor RVAD seem to influence the outcome. In children who were considered as successfully treated, the Cobb angle decreased from 42 to 18 degrees. CONCLUSION: Non-operative treatment for IIS is successful in 3 out of 4 patients. PMID- 22095411 TI - Synthesis and configuration determination of all enantiopure stereoisomers of the melatonin receptor ligand 4-phenyl-2-propionamidotetralin using an expedient optical resolution of 4-phenyl-2-tetralone. AB - An efficient and practical approach for the synthesis of all four stereoisomers of the MT(2) melatonin receptor ligand 4-phenyl-2-propionamidotetralin (4-P PDOT), each in enantiomerically pure form (ee > 99.9%), was developed. The strategy involved an optical resolution procedure of the key precursor (+/-)-4 phenyl-2-tetralone with the unusual resolving agent (S)-mandelamide, through the formation of four dihydronaphtalene-spiro-oxazolidin-4-one diastereomers. Interestingly, NMR experimental observations in combination with geometric calculations, provided unambiguous configuration assignments of all stereocenters of the key spiro stereoisomers. Cleavage of each single spiro diastereomer under acidic conditions gave enantiopure (R)- or (S)-4-phenyl-2-tetralone, which were then converted to each 4-P-PDOT single enantiomer by using stereoselective reactions. PMID- 22095412 TI - Central nervous system tuberculosis in non-HIV-positive children: a single center, 6 year experience. AB - PURPOSE: The aim of this paper is to describe the imaging features of central nervous system (CNS) tuberculosis on computed tomography (CT) and magnetic resonance imaging (MRI) studies in non-HIV-positive children. MATERIALS AND METHODS: A retrospective descriptive evaluation was conducted on imaging studies obtained from ten children admitted to our hospital over a 6-year period who fulfilled criteria for a diagnosis of CNS tuberculosis. Data were collected with regard to patients' clinical, laboratory and demographic characteristics, as well as results of radiological investigation. RESULTS: We studied ten children, of whom five were boys and five were girls and whose mean age was 4 (range 7 months to 16) years. Neuroradiological findings on the first imaging study were basal meningeal enhancement (100%), hydrocephalus (70%), infarcts (90%), tuberculomas (40%) and cranial nerve involvement (20%). Follow-up studies revealed basal meningeal enhancement, hydrocephalus, and infarcts in all patients, tuberculomas in 70% and cranial nerve involvement in 50%. Only one patient showed a pattern of miliary tuberculosis. CONCLUSIONS: CNS tuberculosis is still an important cause of childhood morbidity and mortality even in nonimmunosuppressed children. Because prompt diagnosis results in earlier treatment, it is crucial to be aware of tuberculous meningitis and its complications at imaging, especially because of the impact on patients' prognosis. PMID- 22095413 TI - Classification of noncalcified coronary atherosclerotic plaque components on CT coronary angiography: impact of vascular attenuation and density thresholds. AB - PURPOSE: The authors assessed the effect of vascular attenuation and density thresholds on the classification of noncalcified plaque by computed tomography coronary angiography (CTCA). MATERIALS AND METHODS: Thirty patients (men 25; age 59 +/- 8 years) with stable angina underwent arterial and delayed CTCA. At sites of atherosclerotic plaque, attenuation values (HU) were measured within the coronary lumen, noncalcified and calcified plaque material and the surrounding epicardial fat. Based on the measured CT attenuation values, coronary plaques were classified as lipid rich (attenuation value below the threshold) or fibrous (attenuation value above the threshold) using 30-HU, 50-HU and 70-HU density thresholds. RESULTS: One hundred and sixty-seven plaques (117 mixed and 50 noncalcified) were detected and assessed. The attenuation values of mixed plaques were higher than those of exclusively noncalcified plaques in both the arterial (148.3 +/- 73.1 HU vs. 106.2 +/- 57.9 HU) and delayed (111.4 +/- 50.5 HU vs. 64.4 +/- 43.4 HU) phases (p<0.01). Using a 50-HU threshold, 12 (7.2%) plaques would be classified as lipid rich on arterial scan compared with 28 (17%) on the delayed phase scan. Reclassification of these 16 (9.6%) plaques from fibrous to lipid rich involved 4/30 (13%) patients. CONCLUSIONS: Classification of coronary plaques as lipid rich or fibrous based on absolute CT attenuation values is significantly affected by vascular attenuation and density thresholds used for the definition. PMID- 22095414 TI - Image-guided microwave ablation of hepatic tumours: preliminary experience. AB - PURPOSE: Microwave thermal ablation (MWA) opens up a new scenario in the field of image-guided tumour ablation thanks to its potential advantages over validated radiofrequency ablation (RFA). In this pilot study, we assessed the technical success, safety and efficacy of MWA in treating hepatic malignancies. MATERIALS AND METHODS: After obtaining informed consent, we enrolled 15 inoperable patients, for a total of 19 lesions (ten metastases, nine hepatocellular carcinoma) with a mean diameter of 47 mm (range 14-78 mm). Mean follow-up was 8 (range 1-14) months. RESULTS: Technical success reached 100%. Complications (one major and one minor) occurred in two cases. Complete ablation, obtained in 68.4% of cases, showed no significant correlation with either cancer histological type or with lesion diameter. At follow-up, treatment failures occurred in 60% of cases; lesion diameter was the only prognostic factor for maintaining complete ablation. CONCLUSIONS: Our preliminary results should encourage further trials of this technique. MWA proved to be feasible and safe in treating advanced-stage liver tumours and represented an additional therapeutic attempt to be validated in further and larger efficacy studies. PMID- 22095415 TI - The role of imaging in the pre- and postoperative evaluation of posterior occipito-cervical fusion. AB - PURPOSE: Occipitocervical fusion is required when the occipitoatlantal joint is unstable. The purpose of this paper is to discuss the role of imaging in the pre- and postoperative evaluation of posterior occipitocervical fusion (POCF), focusing on contoured loop fixation by Hartshill and Songer instrumentation. MATERIALS AND METHODS: We studied 21 patients (eight males, 12 females; age range 6-70 years; mean age 32.6 years) with craniocervical instability who underwent POCF with Hartshill U-shaped rod and Songer sublaminar wires. Pre- and postoperative radiographic, computed tomography (CT) and magnetic resonance (MR) imaging examinations were performed in all patients. A 3- to 6-month period of external orthosis with halo vest, sterno-occipitalmandibular immobiliser (SOMI) brace or Philadelphia collar followed surgery. Follow-up was 12-96 (mean 53.1) months. RESULTS: Clinical assessment using the Frankel scale revealed improvement or deterioration arrest in all but two patients: one with C3 failure and halo destabilisation; the other, who had exhibited myelopathy signs on preoperative MR imaging and persistent basilar impression, showed increasing and progressive neurological deficits despite successful POCF. CONCLUSIONS: Pre- and postoperative imaging is extremely useful in patients scheduled to undergo POCF. Preoperative MR screening of basilar impression associated with possible spinal cord lesions appears mandatory to predict possible deterioration and prevent undesired failure of the operation and it may suggest the need for an alternative surgical approach, such as the transoral approach. PMID- 22095416 TI - MDCT in diagnosing acute aortic syndromes: reviewing common and less common CT findings. AB - Nontraumatic acute thoracic aortic syndromes (AAS) describe a spectrum of life threatening aortic pathologies with significant implications on diagnosis, therapy and management. In this context, multidetector computed tomography (MDCT) is the gold standard due to its intrinsic diagnostic value; its performance approaches 100% sensitivity and specificity, and it is accepted as a first-line modality for suspected acute aortic disease. MDCT allows early recognition and characterisation of acute aortic syndromes as well as the presence of any associated complications - findings that are essential for optimising treatment and improving clinical outcomes. Although classic CT findings have long been known, other unusual signs are continually reported in the medical literature. We reviewed the classic and less common CT findings, correlating them with pathophysiology, timing and management options, to achieve a definite and timely diagnostic and therapeutic definition. PMID- 22095417 TI - Effect of two sitting postures on lumbar sagittal alignment and intervertebral discs in runners. AB - PURPOSE: We evaluated in vivo changes in lumbar lordosis and intervertebral discs in runners and assessed the relationship between these changes and degenerative disc disease in runners with and without a history of low back pain. MATERIALS AND METHODS: Using open upright magnetic resonance (MR) imaging, we prospectively studied changes in lumbar lordosis and intervertebral discs of 25 elite long distance runners in two sitting postures (neutral and extended) before and after 1 h of running and compared the results with disc height and dehydration/degeneration. Seventeen of the 25 runners had a history of low back pain. RESULTS: After 1 h of running, mean lordosis in neutral posture reduced by 4 degrees ; reduction was significant in runners with a history of low back pain. A significant reduction in mean lordosis in extension was not observed. Mean disc height significantly reduced in both postures, without, however, any statistical significance between runners with and without a history low back pain in any posture. Variable degrees of disc dehydration/degeneration were observed in 23 runners (57 discs), more commonly at L5-S1. A significant difference of disc dehydration/degeneration between runners with and without a history of low back pain was not observed. CONCLUSIONS: Intervertebral discs undergo significant strain after 1 h of running that in the long term may lead to low back pain and degenerative disc disease. Runners, especially those with low back pain and degenerative disc disease, should be evaluated after training to preserve the normal lumbar lordosis. PMID- 22095418 TI - Sonography of the small bowel after oral administration of fluid: an assessment of the diagnostic value of the technique. AB - PURPOSE: This study was performed to assess the feasibility and possible advantages of bowel sonography after fluid filling of intestinal loops compared with conventional sonography. MATERIALS AND METHODS: Forty-five consecutive patients with known or suspected coeliac disease (35 females, ten males; age range 11-65 years) prospectively underwent sonography before and after ingestion of 750 ml of an aqueous solution of polyethylene glycol. Results before and after fluid distension were compared to assess whether luminal filling improved small bowel visualisation. RESULTS: Luminal filling improved visualisation of intestinal features (luminal diameter, mucosal folds, parietal layers) in 77.6% of cases (marked, moderate or mild improvement in 2, 16 and 17 patients; 4.4%, 35.5% and 37.7%), respectively, and showed no change or worsening in 20% and 2.2% nine and one patient), respectively. Baseline examination showed abnormal features in 13/25 celiac patients (dilated fluid-filled loops, increased peristalsis, transient intussusception, mesenteric lymph nodes, intraperitoneal fluid). Reexamination after luminal filling showed additional abnormalities in six of the previous 13 and in three further coeliac patients. There were no false positive signs due to fluid administration. CONCLUSIONS: Luminal filling can improve visualisation of bowel walls and fold pattern and may be helpful in selected cases. PMID- 22095419 TI - Aortic-neck dilation after endovascular abdominal aortic aneurysm repair (EVAR): can it be predicted? AB - PURPOSE: This study was performed to evaluate whether dynamic computed tomography (CT) can provide functional vessel information predicting outcomes of aortic neck in patients undergoing endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: Twenty patients with and 20 without AAA were enrolled. Electrocardiographically (ECG)-gated data sets were acquired with a 64-slice CT scanner. Axial pulsatility measurements were taken at three levels: 2 cm above the highest renal artery; immediately below the lowest renal artery; 1 cm below the lowest renal artery. Three independent readers performed the measurements. Systolic and diastolic blood pressures were measured in the brachial artery to calculate arterial-wall distensibility expressed as pressure strain elastic modulus (Ep). Cross-sectional area change, wall distensibility and Ep value were statistically compared. RESULTS: No significant differences were found in terms of Ep values in the suprarenal and juxtarenal level. In the AAA group, a significantly higher value was obtained at the infrarenal level. A subgroup of patients with AAA (45%) had a significantly higher Ep value at the infrarenal level. CONCLUSIONS: Dynamic CT provided insight into the abdominal aorta pathophysiology. Identifying patients with higher infrarenal distensibility could change selection of graft size to improve proximal fixation. PMID- 22095420 TI - Congenital aural atresia treated with floating mass transducer on the round window: 5 years of imaging experience. AB - PURPOSE: The aim of this paper is to illustrate imaging features of patients affected by congenital aural atresia (CAA) before and after treatment with a Vibrant SoundBridge (VSB) device implanted on the round window. MATERIALS AND METHODS: Ten patients (5 males and 5 females; mean age 22.1 years) with CAA underwent preoperative high-resolution computed tomography (HRCT) to estimate the degree of involvement of the middle- and inner-ear structures and highlight radiological landmarks useful for surgical planning. RESULTS: Bilateral CAA, mostly of the mixed type, was present in 7 patients and ossicular chain abnormalities in 16 ears (94% of cases). The round window region was normal in all patients, whereas facial-nerve course and/or caliber abnormalities were present in 6 ears (35.3%). The tympanic cavity was small in 13 ears (76.5%), whereas the mastoid was well pneumatized in 8/17 (47%). CONCLUSIONS: HRCT provides accurate information about anatomy and malformations of the middle and inner ear and can thus assist the surgeon in planning the procedure. PMID- 22095421 TI - Incidence of new foci of hepatocellular carcinoma after radiofrequency ablation: role of multidetector CT. AB - PURPOSE: The authors sought to assess the incidence of new foci of hepatocellular carcinoma (HCC) using multidetector computed tomography (MDCT) in patients treated with radiofrequency ablation (RFA). MATERIALS AND METHODS: Two readers retrospectively reviewed by consensus the follow-up MDCT studies of 125 patients (88 men and 37 women; mean age 68 years) with 141 HCCs (size 1-5.2 cm; mean 2.2 cm) treated with RFA. MDCT follow-up was performed at 1 and 3 months and every 6 12 months thereafter. Reviewers assessed: (1) the presence of new HCC foci in the same liver segment or in a different segment; (2) complete or incomplete tumour ablation; (3) tumour progression. RESULTS: A total of 113 new HCCs (size 0.7-4.8 cm; mean 1.7 cm) were detected in 69/125 (55.2%) patients (mean follow-up 30.38+/ 19.14 months). Of these, 86 (76.1%) new HCCs were multiple (p<0.0001), and 92 (81.4%) occurred in a different segment from that of the treated HCC (p<0.0001). New HCCs were observed in the first 12 months, between 12 and 24 months and after 24 months in 31/69 (44.9%), 24/69 (34.8%) and 14/69 (20.3%) patients, respectively (p=0.175). Mean diseasefree interval was 16.1+/-16.31 (range 1-52) months. Complete tumour ablation was achieved in 132/141 (93.6%) treated HCCs, and tumour progression occurred in 29/141 (20.6%) cases. CONCLUSIONS: In patients with RFA-treated HCCs, MDCT follow-up revealed a high incidence of new HCCs, even after 1 year of follow-up. The new foci tended to be multiple and located in a liver segment different from that of the previously treated nodules. PMID- 22095422 TI - Tumours of the atlas and axis: a 37-year experience with diagnosis and management. AB - PURPOSE: This paper presents a single institution's longterm experience regarding the incidence and management of tumours of the atlas and axis and discusses clinical and imaging findings and treatment options. MATERIALS AND METHODS: We searched the registry of the Istituto Ortopedico Rizzoli for patients admitted and treated for tumours of the upper cervical spine. We identified 62 patients over 37 years, from July 1973 to October 2010. There were 39 male and 23 female patients, with a mean age of 39.5 (range 5-77) years. For each patient, we collected data on clinical presentation, imaging and treatment. Mean follow-up was 10 years. RESULTS: Benign bone tumours were diagnosed in 24 (39%) and malignant tumours in 38 (61%) patients. The most common tumours were bone metastases, followed by osteoid osteomas and chordomas. The atlas was involved in six and the axis in 52 patients; in four patients, both the atlas and axis were involved. The most common clinical presentation was pain, torticollis, dysphagia and neurological deficits. Surgical treatment was performed in 35 patients and conservative treatment, including intralesional methylprednisolone injections and halo-vest immobilisation with or without radiation therapy, chemotherapy or embolisation, in the remaining patients. One patient with osteoblastoma of the atlas had local recurrence. All patients with metastatic bone disease had local recurrence; four of the eight patients with plasmacytoma progressed to multiple myeloma within 1-4 years. All patients with chordomas had two to four local recurrences. Patients with osteosarcomas and chondrosarcoma died owing to local and distant disease progression. CONCLUSIONS: Bone tumours of the cervical spine are rare. However, they should be kept in mind when examining patients with neck pain or neurological symptoms at the extremities. In most cases, only intralesional surgery can be administered. Combined radiation therapy and chemotherapy is indicated for certain tumour histologies. PMID- 22095423 TI - Diagnostic accuracy of second-generation dual-source computed tomography coronary angiography with iterative reconstructions: a real-world experience. AB - PURPOSE: The authors evaluated the diagnostic accuracy of second-generation dual source (DSCT) computed tomography coronary angiography (CTCA) with iterative reconstructions for detecting obstructive coronary artery disease (CAD). MATERIALS AND METHODS: Between June 2010 and February 2011, we enrolled 160 patients (85 men; mean age 61.2+/-11.6 years) with suspected CAD. All patients underwent CTCA and conventional coronary angiography (CCA). For the CTCA scan (Definition Flash, Siemens), we use prospective tube current modulation and 70 100 ml of iodinated contrast material (Iomeprol 400 mgI/ ml, Bracco). Data sets were reconstructed with iterative reconstruction algorithm (IRIS, Siemens). CTCA and CCA reports were used to evaluate accuracy using the threshold for significant stenosis at >=50% and >=70%, respectively. RESULTS: No patient was excluded from the analysis. Heart rate was 64.3+/-11.9 bpm and radiation dose was 7.2+/-2.1 mSv. Disease prevalence was 30% (48/160). Sensitivity, specificity and positive and negative predictive values of CTCA in detecting significant stenosis were 90.1%, 93.3%, 53.2% and 99.1% (per segment), 97.5%, 91.2%, 61.4% and 99.6% (per vessel) and 100%, 83%, 71.6% and 100% (per patient), respectively. Positive and negative likelihood ratios at the per-patient level were 5.89 and 0.0, respectively. CONCLUSIONS: CTCA with second-generation DSCT in the real clinical world shows a diagnostic performance comparable with previously reported validation studies. The excellent negative predictive value and likelihood ratio make CTCA a first-line noninvasive method for diagnosing obstructive CAD. PMID- 22095424 TI - A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part I: Evolving technical choices and survival. AB - PURPOSE: The authors sought to define treatment results according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy between 1977 and 2000 at the Florence (FLO) and Brescia (IRA) Radiation Oncology centres were studied. Five-year overall (OS) and disease specific (DSS) actuarial survival rates in the different pathological, clinical and therapeutic subgroups were calculated, along with the actuarial local regional control (LRC) probability. RESULTS: At univariate analysis, survival and local control rates were significantly better in the more recent accrual periods and in the more favourable disease presentations; treatment-related parameters mainly affect LRC. At multivariate analysis, patient- and disease-related factors had a more evident prognostic effect than did therapeutic factors, although dose to the nasopharynx and treatment technique had a marginally significant impact on DSS and OS. CONCLUSIONS: Results of this benchmark study may be useful for understanding the development of new radio-therapy techniques for NPC, such as three-dimensional conformal radiotherapy (3D-CRT) and particularly intensity modulated radiotherapy (IMRT). PMID- 22095425 TI - A benchmark study on 883 nasopharyngeal cancer patients treated in two Italian centres from 1977 to 2000. Part II: Evolving technical choices and toxicity patterns. AB - PURPOSE: The authors sought to define toxicity patterns according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades. MATERIALS AND METHODS: A total of 883 patients consecutively treated with radiotherapy from 1977 to 2000 at the Florence (FLO) and Brescia (IRA) radiation oncology centres were studied. The crude incidence of late treatment toxicity in the different subgroups of patients was calculated and compared. RESULTS: Higher total and fractional doses and the "older" treatment techniques were related with an increased incidence of the main late effects of treatment. More recently treated patients experienced less treatment-related complications. CONCLUSIONS: Results of this benchmark study may have implications for understanding and developing new radiotherapy techniques, such as three dimensional conformal radiotherapy (3D-CRT) and, in particular, intensity modulated radiotherapy (IMRT) for NPC patients. PMID- 22095426 TI - Metabolite detection of pancreatic carcinoma by in vivo proton MR spectroscopy at 3T: initial results. AB - PURPOSE: The authors sought to identify metabolic features of pancreatic carcinoma by in vivo proton magnetic resonance (MR) spectroscopy at 3 Tesla. MATERIALS AND METHODS: Forty healthy volunteers and 40 patients with pancreatic carcinoma confirmed by histopathology underwent T2-weighted imaging for localisation of the single voxel. Respiration-triggered (1)H MR spectroscopy was used to detect metabolites in normal pancreas and cancerous tissue. All spectral data were processed with SAGE software. Unsuppressed water at 4.7 ppm was used as an internal reference to determine metabolite concentrations. Each ratio among the different peak areas was statistically evaluated between normal pancreas and pancreatic carcinoma. RESULTS: The following five groups of spectra were detected: unsaturated fatty acids (-CH = CH-) at 5.4 ppm; residual water at 4.7 ppm; choline metabolites at 3.2 ppm; unsaturated fatty acids (-CH2-CH = CH-) or a combination of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), glutamine, glutamate, macromolecules and unsaturated fatty acids (-CH2-CH = CH-) at 2.0 ppm and lipids at 1.3 ppm. Ratio of lipids to unsuppressed water in normal pancreas was statistically greater than that in pancreatic cancer (p=0.004). Ratio of choline to unsuppressed water in normal pancreas was statistically greater than that in pancreatic cancer (p=0.0001). Ratio of fatty acids (-CH = CH ) to lipids in normal pancreas was statistically lower than that in pancreatic cancer (p=0.006). CONCLUSIONS: Compared with normal pancreas, pancreatic carcinoma has a higher ratio of fatty acids (-CH = CH-) to lipids and lower ratios of lipids to unsuppressed water and choline to unsuppressed water at 3T. PMID- 22095427 TI - Radiofrequency ablation of renal cell carcinoma in patients with a solitary kidney: a retrospective analysis of our experience. AB - PURPOSE: This study was done to evaluate the feasibility and safety of radiofrequency ablation (RFA) of renal cell carcinomas (RCCs) in patients with solitary kidney. MATERIALS AND METHODS: Seven patients (two men, five women; age range 52-70 years; mean age 59.7 years) were treated under computed tomography (CT) and ultrasound (US) guidance. Three patients had single lesions, and the remaining four had multiple lesions. Seventeen lesions (4 cortical, 13 exophytic, maximum diameter range 12-40 mm, mean 21.0 mm) not located close to the renal pelvis were treated. CT or magnetic resonance (MR) imaging follow-up studies were obtained for all patients at the end of the procedure and at 1, 3, 6 and 12 months; serum creatinine was also monitored. RESULTS: Ten ablation sessions were performed. In two patients, a perinephric haematoma was detected, and one of these patients had two episodes of self-limiting haematuria. Contrast-enhanced CT and MR imaging at the end of the procedure and at 1 month demonstrated 100% technical success; these results were confirmed at 3, 6 and 12 month. Fisher's test comparing serum creatinine obtained 1 day before and 1 day after the procedure showed no case of acute renal failure (mean serum creatinine 24 h before the procedure 1.02 mg/dl; mean serum creatinine 24 h after the procedure 0.95 mg/dl; p=0.114; not significant). Serum creatinine at follow-up was always within the normal range. CONCLUSIONS: Radiofrequency ablation in the solitary kidney is a safe and effective procedure for treating RCC. PMID- 22095428 TI - Phytotoxkit: a critical look at a rapid assessment tool. AB - Terrestrial plant toxicity testing contributes critical information to many site risk assessments, but standardized tests can be labor-intensive, use large amounts of soil, and employ long test durations. The Phytotoxkit (MicroBioTests, Environmental Bio-Detection Products) minimizes the time and cost associated with terrestrial plant testing with a unique test setup, a shorter test duration, and less soil. However, the sensitivity of the test remains an open question. In this research, the Phytotoxkit and the standardized Environment Canada terrestrial plant toxicity test (definitive test) are compared using a parallel testing approach. Three different scenarios were examined: a multiconcentration test, in which an inhibiting concentration (ICp) was derived from chemically amended soils; a soil remediation test, in which plant growth in a remediated soil was compared to the original contaminated soil; and a site soil test, in which plant growth in a contaminated soil was compared to a reference soil. The contaminants tested were boric acid, Cr(VI) with cyclodextrin as a remediation agent, and petroleum hydrocarbons. Trifolium pratense (red clover) was used in the first and second scenarios, and six different plant species were used in the third scenario. In the first scenario, the Phytotoxkit results compared well with the definitive test results after 5 and 7 d of exposure. In the second scenario, the Phytotoxkit results agreed with the definitive test when evaluating the effectiveness of remediation. In the third scenario, the Phytotoxkit results were often not in agreement with the results from the definitive test. The reduced sensitivity of the Phytotoxkit in the third scenario may be driven by test unit design, as plant roots are separated from soil by filter paper. PMID- 22095429 TI - Endothelial progenitor cells: current issues on characterization and challenging clinical applications. AB - Since their discovery about a decade ago, endothelial precursor cells (EPC) have been subjected to intensive investigation. The vision to stimulate respectively suppress a key player of vasculogenesis opened a plethora of clinical applications. However, as research opened deeper insights into EPC biology, the enthusiasm of the pioneer era has been damped in favour of a more critical view. Recent research is focused on three major questions: The fact that the number of EPC in peripheral blood is exceedingly low has consistently raised suspicion whether these cells can plausibly have an impact on physiological or pathophysiological processes. Secondly, whereas the key role of EPC in tumourigenesis has been strongly emphasized by various groups in the past, recent publications are challenging this hypothesis. Thirdly, the lack of consensus on EPC-defining markers and standardized protocols for their detection have repeatedly led to difficulties concerning comparability between papers. In this current review, an overview on recent findings on EPC biology is given, their challenging clinical implications are discussed and the perplexity underlying the current controversial debate is illustrated. PMID- 22095436 TI - Intestinal bacterial translocation in rats with cirrhosis is related to compromised Paneth cell antimicrobial host defense. AB - Liver cirrhosis is associated with bacterial translocation (BT) and endotoxemia. Most translocating bacteria belong to the common intestinal microbiota, suggesting a breakdown of intestinal barrier function. We hypothesized that diminished mucosal antimicrobial host defense could predispose to BT. Two rodent models of portal hypertension with increased BT were used, CCl(4)-induced ascitic cirrhosis and 2-day portal vein-ligated (PVL) animals. BT was assessed by standard microbiological techniques on mesenteric lymph nodes. Total RNA was isolated systematically throughout the intestinal tract, and expression of Paneth cell alpha-cryptdins and beta-defensins was determined by real-time quantitative polymerase chain reaction (qPCR). To determine functional consequences, mucosal antimicrobial activity was assessed with a fluorescence-activated cell sorting assay. BT was detectable in 40% of rats with cirrhosis. Compared with the group without BT, these animals exhibited diminished intestinal Paneth cell alpha cryptdin 5 and 7 expression. In contrast, PVL was associated with BT in all animals but did not affect antimicrobial peptides. The decrease in Paneth cell antimicrobials was most pronounced in the ileum and the coecum. Other antimicrobials showed no changes or even an induction in the case of BT at different sites. Antimicrobial activity toward different commensal strains was reduced, especially in the distal ileum and the cecum in experimental cirrhosis with BT (excluding PVL). CONCLUSION: Compromised Paneth cell antimicrobial host defense seems to predispose to BT in experimental cirrhosis. Understanding this liver-gut axis including the underlying mechanisms could help us to find new treatment avenues. PMID- 22095437 TI - Meta-analysis of phase III trials of docetaxel alone or in combination with chemotherapy in metastatic breast cancer. AB - PURPOSE: Whether combination chemotherapy offers an advantage over sequential therapy in metastatic breast cancer (MBC) is still an unsettled issue. Polychemotherapy regimens containing taxanes has been shown to increase overall survival (OS), time to tumor progression (TTP), and overall response rate (ORR) when compared with regimens that did not contain a taxanes, while taxane-based doublets have a statistically significant benefit over single-agent taxane only for progression-free survival. However, the term "taxanes" generally includes both paclitaxel and docetaxel, drugs with different clinical activity. Aim of this work is to compare OS, TTP, and ORR in patients with MBC receiving docetaxel alone or in combination with chemotherapy using a formal meta-analysis. METHODS: We performed a systematic review of all published trials comparing docetaxel alone or in combination with other chemotherapeutic agents in MBC. RESULTS: Three randomized clinical trials including 1,313 patients were retrieved. A significant reduction of risk ratio was found in TTP (P <= 0.0001) but not in OS (P = 0.48) or ORR (P = 0.10) for patients treated with a chemotherapy agent plus docetaxel compared with docetaxel alone. Treatment with docetaxel alone is associated with a lower incidence of grade 3 diarrhea and stomatitis (diarrhea, P = 0.011; stomatitis, P = 0.0004). CONCLUSION: Combination chemotherapy regimens with docetaxel show a statistically significant advantage for TTP, but not for OS and ORR in MBC. This review confirms that it is unlikely that any single agent or combination chemotherapy regimen will emerge as superior in MBC, due to its heterogeneous nature. PMID- 22095438 TI - Effectiveness of semi-quantitative multiphase dynamic contrast-enhanced MRI as a predictor of malignancy in complex adnexal masses: radiological and pathological correlation. AB - OBJECTIVES: To determine whether threshold criteria using semi-quantitative multiphase-dynamic contrast-enhanced magnetic resonance imaging (DCE- MRI) can improve prediction of malignancy in complex adnexal masses. METHODS: MRI features of 70 complex adnexal masses with enhancing components in 63 patients were reviewed and correlated with histopathology (n = 67) or radiological follow-up (n = 3). Masses were categorised as benign (n = 34) or borderline/invasive malignant (n = 36). Borderline lesions (n = 6) were also analysed separately. Using the semi-quantitative breast analysis software, regions of interest were drawn around the most avidly enhancing component of each lesion. Maximum absolute enhancement of signal intensities (SI(max)), maximum relative enhancement (SI(rel)) and wash in rate (WIR) were recorded. Optimal threshold criteria were established to predict borderline/invasive malignancy. RESULTS: There was a significant difference in mean SI(max) (P < 0.05), SI(rel) (P < 0.01) and WIR (P < 0.001) between benign and borderline/invasive malignant groups. A cut-off WIR >= 9.5 l/s had a specificity of 88% and positive predictive value of 86% for predicting malignancy, significantly better than conventional MRI (62%, P < 0.01). WIR <8.2 l/s had a negative predictive value of 94%. CONCLUSION: Threshold criteria using semi-quantitative multiphase DCE-MRI improves specificity in the prediction of malignancy in complex adnexal masses with enhancing components and is complementary to standard qualitative assessment. KEY POINTS: Semi-quantitative DCE-MRI threshold criteria are effective for predicting ovarian malignancy. The surgical approach may be altered depending on DCE-MRI threshold criteria analysis. Borderline tumours demonstrate significant overlap with benign lesions using DCE-MRI threshold criteria. PMID- 22095439 TI - Benefits of the quality assured double and arbitration reading of mammograms in the early diagnosis of breast cancer in symptomatic women. AB - OBJECTIVES: To address the benefits of double and arbitration reading regarding tumour detection rates, percentage of in situ tumours, and number (of patients) needed to send for expert reading (number needed to treat; NNT) for one additional tumour finding. METHODS: QuaMaDi is a quality assured breast cancer diagnosis programme; with two-view mammography (craniocaudal, mediolateral oblique) and, in case of breast density ACR 3 or 4, routine ultrasound imaging; and with independent double reading of all images. A consecutive sample of symptomatic women, i.e. women at risk for breast cancer, women aged 70 and above, and/or women with preceding BI-RADS III findings, was analysed. RESULTS: 28,558 mammograms were performed (mean age of women: 57.3 [standard deviation: 12.3] years). Discordant findings were present in 3,837 double readings and were sent for arbitration reading. After histopathological assessment, 52 carcinomas were found (thereof 32% in situ). These carcinomas accounted for 1.8 tumours per 1,000 examinations in the total cohort and increased the tumour detection rate up to 16.4/1,000. The NNT in discordant cases was 74. CONCLUSION: Double and arbitration reading appears to be a useful tool to ensure the quality of early detection of breast lesions in symptomatic women during indication-based, standardised mammography. KEY POINTS: * Quality assured breast cancer diagnosis is feasible outside organised screening structures. * Double and arbitration reading is beneficial for populations ineligible for screening. * Double and arbitration reading increases the tumour detection rate. * Double and arbitration reading increases the percentage of in situ cancers. PMID- 22095440 TI - The quality of life trajectory of resected gastric cancer. AB - BACKGROUND: Few studies describe quality of life (QoL) outcomes following gastrectomy for gastric cancer using a validated instrument. The gastric cancer module for the Functional Assessment of Cancer Therapy system of QoL measurement tools (FACT-Ga) was utilized to determine the changes in QoL following gastrectomy, and during the disease course. METHODS: In 43 patients undergoing gastrectomy for gastric cancer, outcome such as complications, recurrence, and survival were annotated. Karnofsky performance status (KPS) and QoL were determined preoperatively and at each follow-up visit. RESULTS: Nineteen (44%) patients and 24 (56%) patients underwent partial gastrectomy (PG) and total gastrectomy (TG), respectively. Complications occurred in 30%, and one mortality (2.3%) occurred. Median survival was 23 months. KPS, FACT-G, and FACT-Ga scores all decreased after surgery, and normalized by 6 months. There was no significant difference in QoL in patients who had a PG or TG, although the type of gastrectomy did affect KPS. QoL dropped on average 4.4 +/- 3.6 months prior to death. CONCLUSIONS: Surgery adversely affects QoL for up to 6 months. Thereafter, QoL mirrors changes in disease status. More studies are required to document the QoL cost-benefit ratio in gastric cancer, which often is accompanied by short survival benefits. PMID- 22095441 TI - ARID2: a new tumor suppressor gene in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, however, genetic-environmental interactions and mechanisms associated with the development of HCC remains largely unclear. Our recent work described novel inactivating mutations of ARID2 (AT-rich interactive domain 2) in four major subtypes of HCC through exomic sequencing of ten HCV-associated HCCs and subsequent evaluation of the tumors from additional affected individuals. Here, we summarize the current knowledge about the relevance of ARID2 in HCC and the implication in future patient care. PMID- 22095442 TI - Dietary supplementation with methylseleninic acid, but not selenomethionine, reduces spontaneous metastasis of Lewis lung carcinoma in mice. AB - The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA), in comparison with selenomethionine (SeMet), on spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice using intramuscular and subcutaneous injection models. Mice were fed AIN93G control diet or that diet supplemented with MSeA or SeMet at 2.5 mg selenium/kg for 4 weeks at which time they were injected intramuscularly or subcutaneously with 2.5 * 10(5) viable LLC cells. Experiments were terminated 2 weeks later for mice injected intramuscularly or 2 weeks after surgical removal of primary tumors from mice subcutaneously injected with cancer cells. Dietary supplementation with MSeA significantly reduced pulmonary metastatic yield when compared with the controls (p < 0.05) in both models; however, SeMet did not have such an effect. Supplementation with MSeA significantly decreased plasma concentrations of urokinase-type plasminogen activator (p < 0.05) and plasminogen activator inhibitor-1 (p < 0.05). Furthermore, MSeA significantly reduced plasma concentrations of vascular endothelial growth factor (p < 0.05), fibroblast growth factor basic (p < 0.05) and platelet-derived growth factor-BB (p < 0.05) when compared with the controls. Selenomethionine did not affect any of the aforementioned measurements. These results demonstrate that MSeA reduces spontaneous metastasis of LLC in mice, perhaps through inhibition of the urokinase plasminogen activator system and reducing angiogenesis. PMID- 22095443 TI - Evaluation of the energy efficiency of enzyme fermentation by mechanistic modeling. AB - Modeling biotechnological processes is key to obtaining increased productivity and efficiency. Particularly crucial to successful modeling of such systems is the coupling of the physical transport phenomena and the biological activity in one model. We have applied a model for the expression of cellulosic enzymes by the filamentous fungus Trichoderma reesei and found excellent agreement with experimental data. The most influential factor was demonstrated to be viscosity and its influence on mass transfer. Not surprisingly, the biological model is also shown to have high influence on the model prediction. At different rates of agitation and aeration as well as headspace pressure, we can predict the energy efficiency of oxygen transfer, a key process parameter for economical production of industrial enzymes. An inverse relationship between the productivity and energy efficiency of the process was found. This modeling approach can be used by manufacturers to evaluate the enzyme fermentation process for a range of different process conditions with regard to energy efficiency. PMID- 22095444 TI - The influence of social deprivation on length of hospitalisation. AB - The implementation of activity-based payment system named T2A-tarification a l'activite-in 2004 profoundly modified the financing of French hospitals. Presently applied to activities concerning medicine, surgery and obstetrics, the pricing for these activities was developed using the National Costs Study. The considerable differences observed between costs in the private sector and those in the public sector are in part justified, by the latter, by caring for patients with social deprivation. The goal of this study is to measure the influence of social deprivation on the length of hospitalisation. A survey on inpatient social deprivation was carried out from November to December 2008 by the French Ministry of Health (Department of Research, Study, Evaluation and Statistics-DREES, and technical agency of Hospital information-ATIH). Four dimensions of social deprivation were taken into consideration after a previous qualitative study: social isolation, quality of housing, level of income and access to rights. The sample is based on 27 hospitals, including public and private (for-profit and not for-profit), representing 57,175 stays, 6,800 of which were patients with social deprivation. After multivariate analyses adjusted for age, severity of illness and DRG, we found that there was a longer length of stay for inpatients with social deprivation (+16%), and in particular for patients living in social isolation (+17%) and for patients with inadequate housing (+17%). The impact of low income on the length of stay is less important. However, low income associated with inadequate housing significantly increases lengths of stay (+24%). PMID- 22095445 TI - Endothelial paxillin and focal adhesion kinase (FAK) play a critical role in neutrophil transmigration. AB - During an inflammatory response, endothelial cells undergo morphological changes to allow for the passage of neutrophils from the blood vessel to the site of injury or infection. Although endothelial cell junctions and the cytoskeleton undergo reorganization during inflammation, little is known about another class of cellular structures, the focal adhesions. In this study, we examined several focal adhesion proteins during an inflammatory response. We found that there was selective loss of paxillin and focal adhesion kinase (FAK) from focal adhesions in proximity to transmigrating neutrophils; in contrast the levels of the focal adhesion proteins beta1-integrin and vinculin were unaffected. Paxillin was lost from focal adhesions during neutrophil transmigration both under static and flow conditions. Down-regulating endothelial paxillin with siRNA blocked neutrophil transmigration while having no effect on rolling or adhesion. As paxillin dynamics are regulated partly by FAK, the role of FAK in neutrophil transmigration was examined using two complementary methods. siRNA was used to down-regulate total FAK protein while dominant-negative, kinase-deficient FAK was expressed to block FAK signaling. Disruption of the FAK protein or FAK signaling decreased neutrophil transmigration. Collectively, these findings reveal a novel role for endothelial focal adhesion proteins paxillin and FAK in regulating neutrophil transmigration. PMID- 22095446 TI - Preparation and properties of a drug release membrane of mitomycin C with N succinyl-hydroxyethyl chitosan. AB - A novel drug loaded membrane made of N-succinyl-hydroxyethyl chitosan and mitomycin C was used as an implant for glaucoma filtering surgery. The characteristics of the membrane, such as FTIR, equilibrium water content, swelling ratio, permeability, and drug release in vitro were determined. The L929 fibroblast inhibition of drug loaded membranes was compared to hydroxyethyl chitosan film and blank control, detecting by MTT. The biodegradability and biocompatibility were evaluated by implanting membranes into the subcutaneous tissue and muscle of rats. FTIR indicated mitomycin C was introduced. The experimental results indicated the drug loaded membrane was effective on the swelling property, permeability, and drug release in vitro. Cell culture experimental results demonstrated that the destination membrane inhibited fibroblast proliferation. In vivo, the membranes showed bioabsorption and biocompatibility. The experimental results provide a theoretical basis for the future development of the drug loaded membrane as an implant for increasing the success rate of filtering surgery. PMID- 22095447 TI - Engineering of erythrocyte-based drug carriers: control of protein release and bioactivity. AB - This work reports the fabrication of layer-by-layer (LbL) polyelectrolyte coated erythrocyte carriers that provide a simple means for controlling the burst and subsequent release of lysozyme. Erythrocytes were loaded with RITC-lysozyme as model compound via the hypotonic dialysis method. An encapsulation efficiency of 41.6% and a loading amount of 12.7 pg/cell was achieved. It is demonstrated that these carriers maintain their shape and integrity similar to natural erythrocytes after the encapsulation procedures, and achieve a uniform distribution of the encapsulated lysozyme. The erythrocyte carriers were fixed with glutaraldehyde and then successfully coated with biocompatible polyelectrolytes, poly-L: -lysine hydrobromide and dextran sulfate, using the LbL method. It is demonstrated that the release profile of the encapsulated macromolecule can be regulated by adjusting the number of polyelectrolyte layers. Furthermore by adjusting the concentrations of the cross linking agent the activity of the encapsulated lysozyme can be well preserved. These core-shell microcapsules, consisting of erythrocytes loaded with bioactive substances and coated with a polyelectrolyte multilayer shell, hold promise for a new type of biocompatible and biodegradable drug delivery system. PMID- 22095448 TI - Prolonged release from PLGA/HAp scaffolds containing drug-loaded PLGA/gelatin composite microspheres. AB - Porous scaffolds that can prolong the release of bioactive factors are urgently required in bone tissue engineering. In this study, PLGA/gelatin composite microspheres (PGMs) were carefully designed and prepared by entrapping poly(L: lactide-co-glycolide) (PLGA) microspheres (PMs) in gelatin matrix. By mixing PGMs with PLGA solution directly, drug-loaded PLGA/carbonated hydroxyapatite (HAp)/PGMs composite scaffolds were successfully fabricated. In vitro release of fluorescein isothiocyanate-dextran (FD70S) as a model drug from the scaffolds as well as PMs and PGMs was studied by immersing samples in phosphate buffered saline (pH = 7.4) at 37 degrees C for 32 days. Compared with PMs, PGMs and PLGA/HAp/PGMs scaffolds exhibited slow and steady release behavior with constant release rate and insignificantly original burst release. The swelling of PGMs, diffusion of drugs, and degradation of polymer dominated the release behaviors synergistically. The PLGA/HAp/PGMs scaffold offers a novel option for sequential or simultaneous release of several drugs in terms of bone regeneration. PMID- 22095449 TI - Directly created electrostatic micro-domains on hydroxyapatite: probing with a Kelvin Force probe and a protein. AB - Micro-domains of modified surface potential (SP) were created on hydroxyapatite films by direct patterning by mid-energy focused electron beam, typically available as a microprobe of Scanning Electron Microscopes. The SP distribution of these patterns has been studied on sub-micrometer scale by the Kelvin Probe Force Microscopy method as well as lysozyme adsorption. Since the lysozyme is positively charged at physiological pH, it allows us to track positively and negatively charged areas of the SP patterns. Distribution of the adsorbed proteins over the domains was in good agreement with the observed SP patterns. PMID- 22095450 TI - Development, characterization, and applications of a novel estrogen receptor beta monoclonal antibody. AB - The role of estrogen receptor alpha (ERalpha) in breast cancer has been studied extensively, and its protein expression is prognostic and a primary determinant of endocrine sensitivity. However, much less is known about the role of ERbeta and its relevance remains unclear due to the publication of conflicting reports. Here, we provide evidence that much of this controversy may be explained by variability in antibody sensitivity and specificity and describe the development, characterization, and potential applications of a novel monoclonal antibody targeting full-length human ERbeta and its splice variant forms. Specifically, we demonstrate that a number of commercially available ERbeta antibodies are insensitive for ERbeta and exhibit significant cross-reaction with ERalpha. However, our newly developed MC10 ERbeta antibody is shown to be highly specific and sensitive for detection of full-length ERbeta and its variant forms. Strong and variable staining patterns for endogenous levels of ERbeta protein were detected in normal human tissues and breast tumors using the MC10 antibody. Importantly, ERbeta was shown to be expressed in a limited cohort of both ERalpha positive and ERalpha negative breast tumors. Taken together, these data demonstrate that the use of poorly validated ERbeta antibodies is likely to explain much of the controversy in the field with regard to the biological relevance of ERbeta in breast cancer. The use of the MC10 antibody, in combination with highly specific antibodies targeting only full-length ERbeta, is likely to provide additional discriminatory features in breast cancers that may be useful in predicting response to therapy. PMID- 22095451 TI - Comment on "Visual layout modulates Fitts's law: the importance of first and last positions". AB - Pratt, Adam, and Fischer (2007) investigated the effect of surrounding targets on the time it took to move to an individual target and found that the movement time to a central target was above the Fitts's law line related to the first and last targets. They explained their results in terms of a "visuomotor hypothesis." Here, an alternative explanation is given in terms of a previously validated model of the "available target width" that is determined by the size of the target and the width of the finger pad that is being used to hit the target. PMID- 22095452 TI - The association between insulin levels and cortical bone: findings from a cross sectional analysis of pQCT parameters in adolescents. AB - Recent studies suggest that patients with type 2 diabetes mellitus are at increased risk of fracture, possibly because hyperinsulinemia is a risk factor for low bone mineral density, which may in turn be a consequence of a lipotoxic effect of visceral and/or intramuscular fat on bone. In the current study, we investigated whether insulin plays a role in cortical bone development by performing a cross-sectional study based on the Avon Longitudinal Study of Parents and Children (ALSPAC), where we examined associations between fasting insulin levels and peripheral quantitative computed tomography (pQCT) parameters as assessed at the mid-tibia in 2784 boys and girls with a mean age 15.5 years. In particular, we wished to examine whether associations that we observed were independent of body composition, including intramuscular fat. We found that insulin was inversely related to cortical bone mineral density (BMD(C)) after adjustment for age and after further adjustment for height, muscle cross sectional area (MCSA), subcutaneous fat (SAT), and muscle density (MD), which is inversely related to intramuscular fat (-0.018, 95% confidence interval [CI] 0.030, -0.006, p < 0.0001). Insulin was positively related to periosteal circumference (PC) after adjusting for age (0.015, 95% CI 0.003, 0.027, p = 0.015; beta = change per 50% increase in insulin), but this changed to an inverse association after additional adjustment for height and body composition (-0.013, 95% CI -0.022, -0.003, p = 0.008). Path analyses revealed inverse associations between insulin and PC via a direct pathway (-0.012, 95% CI -0.022, -0.003, p = 0.01) and via MD (-0.002, 95% CI -0.004, -0.001, p = 0.0004), and positive associations between insulin and PC via SAT (0.013, 95% CI 0.009, 0.016, p < 0.0001) and MCSA (0.015, 95% CI 0.010, 0.020, p < 0.0001). In conclusion, we found an inverse relationship between insulin and PC via intramuscular fat, suggesting a lipotoxic effect on bone. However, an inverse association between insulin and both PC and BMD(C) persisted after adjusting for all body composition variables, suggesting insulin also acts to inhibit bone development via additional pathways yet to be elucidated. PMID- 22095453 TI - An integrated simulator for endolaryngeal surgery. AB - The acquisition and maintenance of skills in transoral microlaryngeal surgery requires extended practice. Effective mentoring of such single-operator procedures is not possible, making it important for trainee surgeons to acquire basic skills outside of the operating room before participating in procedures on patients. Currently available training simulators use either synthetic materials or human tissue, both of which have limitations. We have designed a hybrid simulator that incorporates a porcine larynx in to an airway training manikin, providing both accurate airway anatomy and natural tissue handling characteristics. This model allows training in the skills required for suspension laryngoscopy and the resection of laryngeal lesions. Further applications could include development of surgical techniques and instruments, and use in accreditation of training and revalidation of trained surgeons. PMID- 22095455 TI - Structure of the DNA-bound T-box domain of human TBX1, a transcription factor associated with the DiGeorge syndrome. PMID- 22095454 TI - Molecular mimicry as a mechanism of autoimmune disease. AB - A variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases. One mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens. Molecular mimicry has typically been characterized on an antibody or T cell level. However, structural relatedness between pathogen and self does not account for T cell activation in a number of autoimmune diseases. A proposed mechanism that could have been misinterpreted for molecular mimicry is the expression of dual T cell receptors (TCR) on a single T cell. These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response. In this review, we briefly discuss what is known about molecular mimicry followed by a discussion of the current understanding of dual TCRs. Finally, we discuss three mechanisms, including molecular mimicry, dual TCRs, and chimeric TCRs, by which dual reactivity of the T cell may play a role in autoimmune diseases. PMID- 22095456 TI - Signalling plasticity and energy saving in a tropical bushcricket. AB - Males of the tropical bushcricket Mecopoda elongata synchronize their acoustic advertisement signals (chirps) in interactions with other males. However, synchrony is not perfect and distinct leader and follower roles are often maintained. In entrainment experiments in which conspecific signals were presented at various rates, chirps displayed as follower showed notable signal plasticity. Follower chirps were shortened by reducing the number and duration of syllables, especially those of low and medium amplitude. The degree of shortening depended on the time delay between leader and follower signals and the sound level of the entraining stimulus. The same signal plasticity was evident in male duets, with the effect that the last syllables of highest amplitude overlapped more strongly. Respiratory measurements showed that solo singing males producing higher chirp rates suffered from higher metabolic costs compared to males singing at lower rates. In contrast, respiratory rate was rather constant during a synchronous entrainment to a conspecific signal repeated at various rates. This allowed males to maintain a steady duty cycle, associated with a constant metabolic rate. Results are discussed with respect to the preference for leader signals in females and the possible benefits males may gain by overlapping their follower signals in a chorus. PMID- 22095457 TI - [Principles and new concepts in computer-navigated total hip arthroplasty]. AB - Combined component placement of cup and stem is closely correlated to stability, functionality and wear in total hip replacement (THA). Computer-navigated orthopedic surgery offers a reliable control method for a complex three dimensional situation. Imageless navigation systems without the need of preoperative or intraoperative image acquisition and exposure to radiation have been proven to increase the accuracy of positioning the acetabular component and measure intraoperative leg length and offset changes precisely. A new development in this field is the noninvasive external femoral reference marker array system in conjunction with an imageless measurement technique. The future generation of imageless navigation systems will switch from simple measurement tasks to an integral part of the surgical process in navigated THA. The aim will be to find an optimized complementary component orientation with improved postoperative functionality and optimized range of motion without impingement. PMID- 22095458 TI - [Minimally invasive surgery in total hip arthroplasty : Surgical technique of the future?]. AB - AIM: A selective analysis of the latest literature was carried out including prospective clinical controlled studies on the comparison between minimally invasive total hip arthroplasty (MIS) and the conventional technique. METHODS: An online data base search for controlled study designs within the last 3 years (2009-2011) which compared MIS with standard procedures was performed. Data such as operation time, blood loss, Harris hip score, complications and implant positioning were compared. RESULTS: A total of 11 studies which compared the results of 387 MISs and 264 operations on hips with the standard technique were analyzed. In the majority of the studies reduced levels of creatine kinase and myoglobin as well as reduced intraoperative blood loss were reported. In the early postoperative period up to postoperative week 6 significant advantages in the Harris hip score were reported for the MIS patients. Postoperative complications and implant positioning were comparable in both groups. The operation time was significantly longer in the MIS group for some studies. CONCLUSIONS: Minimally invasive techniques in total hip arthroplasty are nowadays no longer seen as just cosmetically attractive but rather as a real improvement for the clinical outcome. In this respect prospective clinically controlled studies within the last 3 years showed advantages in the early postoperative period. PMID- 22095459 TI - [Is shorter really better? : Philosophy of short stem prosthesis designs]. AB - The presently available short hip stem designs show significant differences and can be differentiated into those containing the neck, those partially containing the neck and neck resection designs. In this article the currently available designs will be presented. Except for the Mayo stem there are no long-term results available. There are significant differences between the the systems especially with respect to reproducibility of the individual anatomy of patients therefore DEXA and DSA studies are needed in order to identify problematic stem designs early before clinical failures are produced in a large number of patients. PMID- 22095460 TI - Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix. AB - Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression in tumor cells may enable them to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G polymorphism on risk of high-grade cervical intraepithelial neoplasia (HG CIN) and cervical cancer in a Canadian population. The authors have analyzed 1,372 women from participants recruited between 2001 and 2009 in the ongoing Biomarkers of Cervical Cancer Risk case-control study. A total of 539 women with histologically confirmed HG-CIN and invasive cancer formed the case series, and 833 women with normal cytology served as controls. Cervical specimens were tested for human papillomavirus (HPV) DNA using the MY09/11 PCR protocol and HLA-G alleles where determined using a direct DNA sequencing procedures. HLA-G polymorphisms were not associated with HG-CIN or HPV infection. However, the risk for invasive cancer was significantly increased with the homozygous genotypes HLA G*01:01:02 [odds ratio (OR) = 3.52, 95% confidence interval (CI): 1.43-8.61, p = 0.006], -G*01:06 (OR = 19.1, 95% CI: 2.29-159, p = 0.005) and -G* 3'UTR 14-bp insertion (OR = 2.17, 95% CI: 1.10-4.27, p = 0.020), whereas, the heterozygotic form of the G*01:01:01 wild-type allele was significantly associated with a reduced risk of invasive cancer (OR = 0.31, 95% CI: 0.16-0.59, p < 0.0001) after adjusting for age, HPV infection and ethnicity. These associations were also observed with progression of disease from HG-CIN to invasive cancer among HPV positive women. These results suggest that HLA-G polymorphism is an independent risk factor for the development of invasive cervical cancer. PMID- 22095461 TI - Establishment of an experimental method for detecting circulating miRNAs in BDL mice. AB - Despite its great potency in self-rehabilitation, liver is the most vulnerable organ, and an early minor liver injury is unfortunately undetectable by the traditional assay of aminotransferases; hence, more sensitive and specific biomarkers of minor liver injury have attracted much attention. A number of studies have suggested that circulating microRNAs (miRNAs) are accessible and attractive parameters of early tissue injury. A recent study has found that plasma microRNA-122 is a disease severity-dependent biomarker, and there is an elevated level of microRNA-122 prior to the alteration of aminotransferases in viral, alcohol, and chemical-related hepatic injuries. Since bile duct-ligated (BDL) mice have been well adapted as an effective model of cholestatic hepatic injury, liver fibrosis, liver cirrhosis, and their relevant complications, we hypothesized that detection of circulating miRNAs will probably find its unique utility in BDL model and thus exploited an effective and reliable experimental method of studying serum-based miRNAs in BDL mice. PMID- 22095462 TI - Understanding and Treating Unwanted Trauma Memories in Posttraumatic Stress Disorder. PMID- 22095463 TI - Myocardial tissue engineering: toward a bioartificial pump. AB - Regenerative therapies, including cell injection and bioengineered tissue transplantation, have the potential to treat severe heart failure. Direct implantation of isolated skeletal myoblasts and bone-marrow-derived cells has already been clinically performed and research on fabricating three-dimensional (3-D) cardiac grafts using tissue engineering technologies has also now been initiated. In contrast to conventional scaffold-based methods, we have proposed cell sheet-based tissue engineering, which involves stacking confluently cultured cell sheets to construct 3-D cell-dense tissues. Upon layering, individual cardiac cell sheets integrate to form a single, continuous, cell-dense tissue that resembles native cardiac tissue. The transplantation of layered cardiac cell sheets is able to repair damaged hearts. As the next step, we have attempted to promote neovascularization within bioengineered myocardial tissues to overcome the longstanding limitations of engineered tissue thickness. Finally, as a possible advanced therapy, we are now trying to fabricate functional myocardial tubes that may have a potential for circulatory support. Cell sheet-based tissue engineering technologies therefore show an enormous promise as a novel approach in the field of myocardial tissue engineering. PMID- 22095464 TI - A study of UbcH10 expression and its association with recurrence of meningiomas. AB - BACKGROUND: UbcH10 is an important regulator for the mitotic spindle assembly checkpoint pathway that regulates cell-cycle progression. Overexpression of UbcH10 significantly correlated with advanced tumor grade and high cell proliferation. METHODS: The expression of UbcH10 and Ki-67 in meningioma tissues were evaluated immunohistochemically in 47 patients with meningiomas. The correlation of UbcH10 immunoreactivity with clinicopathological features and the prognostic value of UbcH10 in patients were also analyzed. RESULTS: Immunohistochemistry showed an increase in UbcH10 labeling index in atypical and anaplastic meningiomas versus classical meningiomas (10.53 +/- 5.79% vs. 4.23 +/- 2.85%, P < 0.001). There was a positive correlation between UbcH10 and Ki-67 immunoreactivity (Spearman r = 0.77, P < 0.001). Clinicopathological evaluation suggested that UbcH10 expression was associated with tumor grade and recurrence (P < 0.05). Kaplan-Meier survival analysis and Cox multivariate analysis revealed a significant correlation between high levels of UbcH10 immunoreactivity and high rates of tumor recurrence. CONCLUSION: We conclude that UbcH10 may play important roles in the development of meningioma, high UbcH10 labeling index indicates higher grade of meningioma, and UbcH10 may be a useful molecular marker for predicting the prognosis of meningioma. PMID- 22095465 TI - FACT in Cell Differentiation and Carcinogenesis. PMID- 22095467 TI - Detection of biological uranium reduction using magnetic resonance. AB - The conversion of soluble uranyl ions (UO22+) by bacterial reduction to sparingly soluble uraninite (UO2(s)) is being studied as a way of immobilizing subsurface uranium contamination. Under anaerobic conditions, several known types of bacteria including iron and sulfate reducing bacteria have been shown to reduce U (VI) to U (IV). Experiments using a suspension of uraninite (UO2(s)) particles produced by Shewanella putrefaciens CN32 bacteria show a dependence of both longitudinal (T1) and transverse (T2) magnetic resonance (MR) relaxation times on the oxidation state and solubility of the uranium. Gradient echo and spin echo MR images were compared to quantify the effect caused by the magnetic field fluctuations (T*2) of the uraninite particles and soluble uranyl ions. Since the precipitate studied was suspended in liquid water, the effects of concentration and particle aggregation were explored. A suspension of uraninite particles was injected into a polysaccharide gel, which simulates the precipitation environment of uraninite in the extracellular biofilm matrix. A reduction in the T2 of the gel surrounding the particles was observed. Tests done in situ using three bioreactors under different mixing conditions, continuously stirred, intermittently stirred, and not stirred, showed a quantifiable T2 magnetic relaxation effect over the extent of the reaction. PMID- 22095466 TI - Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol. AB - Liver transplantation is the only definitive treatment for end-stage cirrhosis and fulminant liver failure, but the lack of available donor livers is a major obstacle to liver transplantation. Recently, induced pluripotent stem cells (iPSCs) derived from the reprogramming of somatic fibroblasts, have been shown to resemble embryonic stem (ES) cells in that they have pluripotent properties and the potential to differentiate into all cell lineages in vitro, including hepatocytes. Thus, iPSCs could serve as a favorable cell source for a wide range of applications, including drug toxicity testing, cell transplantation, and patient-specific disease modeling. Here, we describe an efficient and rapid three step protocol that is able to rapidly generate hepatocyte-like cells from human iPSCs. This occurs because the endodermal induction step allows for more efficient and definitive endoderm cell formation. We show that hepatocyte growth factor (HGF), which synergizes with activin A and Wnt3a, elevates the expression of the endodermal marker Foxa2 (forkhead box a2) by 39.3% compared to when HGF is absent (14.2%) during the endodermal induction step. In addition, iPSC-derived hepatocytes had a similar gene expression profile to mature hepatocytes. Importantly, the hepatocyte-like cells exhibited cytochrome P450 3A4 (CYP3A4) enzyme activity, secreted urea, uptake of low-density lipoprotein (LDL), and possessed the ability to store glycogen. Moreover, the hepatocyte-like cells rescued lethal fulminant hepatic failure in a nonobese diabetic severe combined immunodeficient mouse model. CONCLUSION: We have established a rapid and efficient differentiation protocol that is able to generate functional hepatocyte like cells from human iPSCs. This may offer an alternative option for treatment of liver diseases. PMID- 22095468 TI - Determination and pharmacokinetics of [6]-gingerol in mouse plasma by liquid chromatography-tandem mass spectrometry. AB - This study describes the development of a rapid and sensitive high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) assay for the quantification of [6]-gingerol in mouse plasma and application to a pharmacokinetic study after dose ranging in mice. The assay involved a protein precipitation step with acetonitrile and an isocratic elution using a mobile phase consisting of acetonitrile and water containing 0.1% formic acid (80:20 v/v). The multiple reaction monitoring was based on the transition of m/z = 277.2 -> 177.1 for [6]-gingerol and 294.2 -> 137.1 for nonivamide (internal standard). The assay was validated to demonstrate the specificity, linearity, recovery, accuracy, precision and stability. The calibration curves were linear over the wide concentration range of 10-10,000 ng/mL (r >= 0.9988). The lower limit of quantification was 10 ng/mL using a small volume of mouse plasma (20 MUL). The method was successfully applied to a pharmacokinetic study in mice after intravenous injection of [6]-gingerol at 1.5, 3 and 6 mg/kg doses. The pharmacokinetics of [6]-gingerol were linear over the dose range studied as demonstrated by the linear increase in area under the concentration-time curve (AUC(inf)) with no significant change in the systemic clearance (Cl(s)), volume of distribution (V(ss)) and elimination half-life (t(1/2)) as a function of dose. PMID- 22095469 TI - Chemical synthesis of Helicobacter pylori lipopolysaccharide partial structures and their selective proinflammatory responses. AB - Helicobacter pylori is a common cause of gastroduodenal inflammatory diseases such as chronic gastritis and peptic ulcers and also an important factor in gastric carcinogenesis. Recent reports have demonstrated that bacterial inflammatory processes, such as stimulation with H. pylori lipopolysaccharide (LPS), initiate atherosclerosis. To establish the structures responsible for the inflammatory response of H. pylori LPS, we synthesized various kinds of lipid A structures (i.e., triacylated lipid A and Kdo-lipid A compounds), with or without the ethanolamine group at the 1-phosphate moiety, by a new divergent synthetic route. Stereoselective alpha-glycosylation of Kdo N-phenyltrifluoroacetimidate was achieved by use of microfluidic methods. None of the lipid A and Kdo-lipid A compounds were a strong inducer of IL-1beta, IL-6, or IL-8, suggesting that H. pylori LPS is unable to induce acute inflammation. In fact, the lipid A and Kdo lipid A compounds showed antagonistic activity against cytokine induction by E. coli LPS, except for the lipid A compound with the ethanolamine group, which showed very weak agonistic activity. On the other hand, these H. pylori LPS partial structures showed potent IL-18- and IL-12-inducing activities. IL-18 has been shown to correlate with chronic inflammation, so H. pylori LPS might be implicated in the chronic inflammatory responses induced by H. pylori. These results also indicated that H. pylori LPS can modulate the immune response: NF kappaB activation through hTLR4/MD-2 was suppressed, whereas production of IL-18 and IL-12 was promoted. PMID- 22095470 TI - 1alpha,25(OH)2D3-dependent modulation of Akt in proliferating and differentiating C2C12 skeletal muscle cells. AB - We previously reported that 1alpha,25-dihydroxy-vitamin D(3) [1alpha,25(OH)(2)D(3)] induces non-transcriptional rapid responses through activation of Src and MAPKs in the skeletal muscle cell line C2C12. In the present study we investigated the modulation of Akt by the secosteroid hormone in C2C12 cells at proliferative stage (myoblasts) and at early differentiation stage. In proliferating cells, 1alpha,25(OH)(2)D(3) activates Akt by phosphorylation in Ser473 in a time-dependent manner (5-60 min). When these cells were pretreated with methyl-beta-cyclodextrin to disrupt caveolae microdomains, hormone-induced activation of Akt was suppressed. Similar results were obtained by siRNA silencing of caveolin-1 expression, further indicating that hormone effects on cell membrane caveolae are required for downstream signaling. PI3K and p38 MAPK, but not ERK1/2, participate in 1alpha,25(OH)(2)D(3) activation of Akt in myoblasts. The involvement of p38 MAPK in Akt phosphorylation by the hormone probably occurs through MAPK-activated protein kinase 2 (MK2), which is activated by the steroid. In addition, the participation of Src in Akt phosphorylation by 1alpha,25(OH)(2)D(3) was demonstrated using the inhibitor PP2 and antisense oligodeoxynucleotides that suppress Src expression. We also observed that PI3K participates in hormone-induced proliferation. During the early phase of C2C12 cell differentiation 1alpha,25(OH)(2)D(3) also increases Akt phosphorylation and activates Src. Of relevance, Src and PI3K are involved in Akt activation and in MHC and myogenin increased expression by 1alpha,25(OH)(2)D(3). Altogether, these data suggest that 1alpha,25(OH)(2)D(3) upregulates Akt through Src, PI(3)K, and p38 MAPK to stimulate myogenesis in C2C12 cells. PMID- 22095471 TI - Bad habits die hard: the NOEC's persistence reflects poorly on ecotoxicology. PMID- 22095472 TI - MC1R genotypes and risk of melanoma before age 40 years: a population-based case control-family study. AB - The contribution of melanocortin-1 receptor (MC1R) gene variants to the development of early-onset melanoma is unknown. Using an Australian population based, case-control-family study, we sequenced MC1R for 565 cases with invasive cutaneous melanoma diagnosed between ages 18 and 39 years, 409 unrelated controls and 518 sibling controls. Variants were classified a priori into "R" variants (D84E, R142H, R151C, I155T, R160W, D294H) and "r" variants (all other nonsynonymous variants). We estimated odds ratios (OR) for melanoma using unconditional (unrelated controls) and conditional (sibling controls) logistic regression. The prevalence of having at least one R or r variant was 86% for cases, 73% for unrelated controls and 81% for sibling controls. R151C conferred the highest risk (per allele OR 2.57, 95% confidence interval 1.86-3.56 for the case-unrelated-control analysis and 1.70 (1.12-2.60) for the case-sibling-control analysis). When mutually adjusted, the ORs per R allele were 2.23 (1.77-2.80) and 2.06 (1.47-2.88), respectively, from the two types of analysis, and the ORs per r allele were 1.69 (1.33-2.13) and 1.25 (0.88-1.79), respectively. The associations were stronger for men and those with none or few nevi or with high childhood sun exposure. Adjustment for phenotype, nevi and sun exposure attenuated the overall log OR for R variants by approximately 18% but had lesser influence on r variant risk estimates. MC1R variants explained about 21% of the familial aggregation of melanoma. Some MC1R variants are important determinants of early-onset melanoma. The strength of association with melanoma differs according to the type and number of variants. PMID- 22095473 TI - Diagnosis of a female urethral diverticulum using transvaginal contrast-enhanced sonourethrography. AB - The diagnosis of female urethral diverticulum is difficult due to its nonspecific symptoms, and invasive diagnostic procedures are often necessary. We report a case in which the diagnosis was made with contrast-enhanced transvaginal sonourethrography. The microbubble contrast agent could be seen filling the diverticular cavity via its opening. PMID- 22095474 TI - Identification of single nucleotide polymorphisms in the CCNA2 gene and its association with wool density in Rex rabbits. AB - The Rex rabbit is a typical fur breed. Wool density, hair length, wool fineness, and hide area are the main indices of fur quality. We previously found that the CCNA2 gene plays an important role in hair follicle initiation and development, and it is involved in the distinctive wool density of the Rex rabbit. It is an important candidate gene for wool density selection through marker-assisted selection. We conducted an association study to identify single nucleotide polymorphisms (SNPs) within the CCNA2 gene and their ligands associated with wool density. Using PCR-RFLP technology, we discovered two SNPs (129G>A and 1140G>C) of the CCNA2 gene. Allele frequencies of these two SNPs were investigated and evaluated by the chi(2) test in 100 Rex rabbits. The two SNPs were both in Hardy-Weinberg equilibrium. We also looked for a potential association of these SNPs with fur traits in 100 Rex rabbits. Rex rabbits with the GG genotype had significantly higher wool density (P < 0.01) than those with other genotypes; the other three fur traits did not differ significantly among the genotypes. In conclusion, the two SNPs of the CCNA2 gene affect wool density in the Rex rabbit. PMID- 22095476 TI - Genes involved in glucose repression and oxidative stress response in the fission yeast Schizosaccharomyces pombe. AB - We looked for changes in gene expression and novel genes that could be involved in the interaction between glucose repression and oxidative stress response in the fission yeast, Schizosaccharomyces pombe, using a constitutive invertase mutant, ird11, which is resistant to glucose. BLAST analysis was made of the S. pombe genome database of cDNAs whose expression ratios differentially decreased or increased upon exposure to mild oxidative stress in this mutant compared to the wild type. Genes with this type of activity were identified as rpl302, encoding 60S ribosomal protein L3, and mpg1, encoding mannose-1-phosphate guanyltransferase; their expression patterns were measured using quantitative real-time PCR. We found that the expression levels of rpl302 and mpg1 genes in ird11 under unstressed conditions were increased compared to those of the wild type. Under stress conditions, the expression levels of the rpl302 gene were decreased in both strains, while mpg1 expression levels remained unchanged. These results suggest that these genes play a role in the response to oxidative stress in this mutant strain. PMID- 22095477 TI - Serum microRNA expression in pregnancies with preeclampsia. AB - Preeclampsia continues to be a mortal disease of pregnant women throughout the world. Recently, geneticists, allied with obstetricians, have opened new frontiers. MicroRNAs (miRNAs) are members of a class of small, noncoding RNA molecules. They are critical posttranscriptional regulators of gene expression. We extracted circulating miRNA from maternal plasma and quantified mir-152 and mir-210. We found up-regulated miR-210 levels as well as down-regulated mir-152 levels in preeclampsia patients.We propose that detection of increased mir-210 levels in maternal serum could be used to improve prediction methods for noninvasive prenatal diagnosis of preeclampsia. PMID- 22095478 TI - Evaluation of genetic dissimilarity in a segregating wine grape population. AB - This study examined the genetic diversity present in a population obtained by crossing two very distinctive varieties of wine grapes (142 progeny from a Riesling x Cabernet Sauvignon cross, including both parents, created at the University of California). The following list of morphological characters were evaluated and found to segregate in this population: cluster weight, cluster length, presence or absence of cluster wings, cluster wing length, number of berries, cluster density (CD), and berry weight. The following juice parameters were also measured: degrees Brix, pH, total phenolics, and titratable acidity. Genetic diversity within this population was estimated through multivariate methods that utilized the Gower index of dissimilarity and UPGMA clustering. The correlations between traits and relative contribution of each variable were also compared. Eleven groups of progeny were distinguished into categories with low, intermediate and high values for cluster weight and cluster density, and low and high values for total phenolics. An inverse correlation was detected between the variables related to production and those related to the quality of the fruit. Principal components analysis demonstrated that all variables examined in this study are important for the correct discrimination of optimal genotypes in this population. These statistical tools can be used to select individuals with the greatest potential for producing high-quality wines. PMID- 22095479 TI - Single primer-based DNA amplification as a suitable and low-cost tool for assessing genetic diversity in mangrove crabs. AB - We used single primer-based DNA markers to assess genetic variability of the mangrove crab, Ucides cordatus, collected from four different localities from Para to Santa Catarina States in Brazil (almost 5000 km distant). Five primers were chosen based on the consistency of the amplified bands and the polymorphism of each locus. A total of 78 loci were amplified in 76 samples; high polymorphism rates were detected in the entire sample (80.8%) and within each locality (73.5-79.5%). Analysis of molecular variance demonstrates significant differences between localities (P < 0.001); however, the Phi(ST) value (0.078) indicates a low level of genetic differentiation, which suggests that U. cordatus larvae can spread over large distances. The variation was distributed among the samples, and most of it was attributed to differences among individuals within localities. Cluster analysis, based on the Jaccard similarity coefficient, and the Mantel test gave similar results to the analysis of molecular variance data. Despite the low level of population structuring, these markers could be used for studying U. cordatus diversity, due to the high level of polymorphism. PMID- 22095480 TI - Molecular cloning of a new wheat calreticulin gene TaCRT1 and expression analysis in plant defense responses and abiotic stress resistance. AB - Calreticulin proteins play essential roles in regulating various metabolic processes and in molecular signal transduction in animals and plants. Using homologous PCR, we screened a cDNA library of the wheat resistance gene Yr5 from a near-isogenic line in the susceptible common wheat variety Taichung 29, which was inoculated with an incompatible race CYR32 of Puccinia striiformis. We isolated a novel full-length cDNA encoding calreticulin protein, which we named TaCRT1. Sequence analyses indicated that TaCRT1 contains an open reading frame of 1287 bp in length; it was deduced to encode 428 amino acids. Clustering analysis showed that TaCRT1 belongs to group III of the calreticulin protein family. Semi-quantitative RT-PCR was used to analyze expression profiles of the isolated gene under biotic and abiotic stresses. Expression of TaCRT1 was suppressed by exogenous application of phytohormones, such as abscisic acid and methyl jasmonate, and by dehydration; but it was induced by CYR32 infection and cold treatment. Based on the expression patterns, we propose that TaCRT1 participates in regulatory processes involved in defense responses and stress resistance in wheat. PMID- 22095481 TI - Establishing references for gene expression analyses by RT-qPCR in Theobroma cacao tissues. AB - Lack of continuous progress in Theobroma cacao (Malvaceae) breeding, especially associated with seed quality traits, requires more efficient selection methods based on genomic information. Reverse transcript quantitative PCR (RT-qPCR) has become the method of choice for gene expression analysis, but relative expression analysis requires various reference genes, which must be stable across various biological conditions. We sought suitable reference genes for various tissues of cacao, especially developing seeds. Ten potential reference genes were analyzed for stability at various stages of embryo development, leaves, stems, roots, flowers, and pod epicarp; seven of them were also evaluated in shoot tips treated either with hormones (salicylate; ethefon; methyl-jasmonate) or after inoculation with the fungus Moniliophthora perniciosa (Marasmiaceae sensu lato). For developing embryos, the three most stable genes were actin (ACT), polyubiquitin (PUB), and ribosomal protein L35 (Rpl35). In the analyses of various tissues, the most stable genes were malate dehydrogenase (MDH), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and acyl-carrier protein B (ACP B). GAPDH, MDH and tubulin (TUB) were the most appropriate for normalization when shoot apexes were treated with hormones, while ACT, TUB and Rpl35 were the most appropriate after inoculation with M. perniciosa. We conclude that for each plant system and biological or ontogenetical condition, there is a need to define suitable reference genes. This is the first report to define reference genes for expression studies in cacao. PMID- 22095475 TI - Expressed sequenced tags profiling of resistant and susceptible Gyr x Holstein cattle infested with the tick Rhipicephalus (Boophilus) microplus. AB - Tick resistance in cattle is mainly found in zebu (Bos indicus) animals, although it is also present in some taurine (B. taurus) breeds. In order to characterize functional genes involved in tick resistance/susceptibility in cattle, two cDNA libraries were generated using skin tissues of selected Holstein x Gyr animals. A total of 2700 high-quality reads from both resistant and susceptible cDNA were assembled into 458 sequences (contigs) and 834 singletons, with a mean size of 447.7 nucleotides. Assignment of homologous proteins by BLASTX revealed 790 (61.1%) and 300 (23.2%) hits in resistant and susceptible cDNA, respectively; 121 of these hits matched bovine proteins. A total of 502 (38.9%) unique sequences were found to have no significant homology with known sequences and were classified as novel sequences. In general, the most abundant sequences consisted of those coding for hypothetical proteins whose function had not yet been determined, in addition to ribosomal proteins, binding proteins and structural proteins, such as keratin and collagen. The most abundant protein found was collagen type III alpha, although ribosomal proteins accounted for half of the 40 most frequent hits. In addition, five matches within the top 40 best hits corresponded to immune response proteins. These sequences could be used for future studies on functional genomics of cattle tick resistance as well as for genomic sequencing projects. PMID- 22095482 TI - High degree of genetic diversity among genotypes of the forage grass Brachiaria ruziziensis (Poaceae) detected with ISSR markers. AB - The grasses of the genus Brachiaria account for 80% of the cultivated pastures in Brazil. Despite its importance for livestock production, little information is available for breeding purposes. Embrapa has a population of B. ruziziensis from different regions of Brazil, representing most of existing variability. This population was used to initiate an improvement program based on recurrent selection. In order to assist the genetic improvement program, we estimated the molecular variability among 93 genotypes of Embrapa's collection using ISSR (inter-simple sequence repeat) markers. DNA was extracted from the leaves. Twelve ISSR primers generated 89 polymorphic bands in the 93 genotypes. The number of bands identified by each primer ranged from two to 13, with a mean of 7.41. Cluster analysis revealed a clearly distinct group, containing most of the B. ruziziensis genotypes apart from the outgroup genotypes. Genetic similarity coefficients ranged from 0.0 to 0.95, with a mean of 0.50 and analysis of molecular variance indicated higher variation within (73.43%) than among species (26.57%). We conclude that there is a high genetic diversity among these B. ruziziensis genotypes, which could be explored by breeding programs. PMID- 22095483 TI - Successful preimplantation genetic aneuploidy screening in Turkish patients. AB - Preimplantation genetic diagnosis is a preventive approach for identifying genetic abnormalities in early stages of reproduction. We used preimplantation genetic aneuploidy screening in 230 cycles of patients with indications of advanced maternal age, recurrent implantation failure, recurrent spontaneous abortions, or severe male factor. Biopsied blastomeres from embryos with six to eight blastomeres on day 3 were fixed and fluorescence in situ hybridization was utilized on chromosomes 13, 16, 18, 21, 22, X, and Y. Among 945 morphologically normal embryos, 314 were diagnosed as chromosomally normal. Trisomy and monosomy were observed in 36% of the cases (18% each). Embryo transfer was used in 144 cycles, resulting in 41 pregnancies. Thirty-seven healthy babies were delivered, with a take-home baby rate of 24.2% and an implantation rate of 22%. We recommend preimplantation genetic aneuploidy screening as a valuable technique to select normal chromosome embryos in order to avoid multiple pregnancies due to the multiple embryo transfers that are normally necessary to ensure pregnancy in poor prognosis in vitro fertilization patients. PMID- 22095484 TI - TransLateral ACL reconstruction: a technique for anatomic anterior cruciate ligament reconstruction. AB - Anatomic placement of the femoral tunnel in anterior cruciate ligament (ACL) reconstruction confers biomechanical advantages over the traditional tunnel position. The anteromedial portal technique for anatomic ACL reconstruction has many well-described technical challenges. This paper describes the TransLateral technique. The technique produces anatomic femoral tunnel placement using direct measurement of the medial wall of the lateral femoral condyle and out to in drilling. All work is carried out through the lateral portal with all viewing via the medial portal. There is no need for an accessory medial portal or hyperflexion of the knee. Level of evidence Expert opinion, Level V. PMID- 22095485 TI - MRI but not arthroscopy accurately diagnoses femoral MPFL injury in first-time patellar dislocations. AB - PURPOSE: The purpose of this study was to investigate whether the femoral part of the medial patellofemoral ligament (MPFL) and its injury can be accurately assessed by standard knee arthroscopy in first-time patellar dislocations or whether preoperative MRI is required to determine injury location in patients where primary MPFL repair is attempted. METHODS: Twelve patients with acute first time dislocations and MRI-based injury of the femoral MPFL and ten patients with recurrent patellar dislocations underwent knee arthroscopy with the use of a 30 degree optic and standard antero-medial and antero-lateral portals. The femoral origin was marked with a cannula under lateral fluoroscopy. Arthroscopic findings of the location of the native femoral MPFL and its injury were compared to the results of MRI and mini-open exploration. RESULTS: In acute cases, the average time from primary patellar dislocation to MRI evaluation was 3 days (1-9 days), and the average time from MRI to surgery was 8 days (3-20 days). The native femoral origin of the MPFL was not visible in any of the chronic cases during arthroscopy. In addition, in all acute cases, arthroscopy failed to directly visualize injury of the femoral MPFL (0 of 12), but mini-open exploration confirmed injury in 11 of 12 patients. This means that arthroscopy was less accurate than MRI for the diagnosis of femoral MPFL injury (P < 0.05). CONCLUSION: The results of this study indicate the limitations of knee arthroscopy in identifying the femoral disruption of the MPFL, a crucial injury that occurs in patellar dislocations. Thus, if a primary MPFL repair is planned, determination of the site of repair should be based on the preoperative MRI. LEVEL OF EVIDENCE: Diagnostic study of non-consecutive patients, Level III. PMID- 22095487 TI - MR perfusion imaging using the arterial spin labeling technique for breast cancer. AB - PURPOSE: To investigate the feasibility of perfusion imaging using an arterial spin labeling (ASL) technique for breast cancer. MATERIALS AND METHODS: Thirteen female patients with primary breast cancers were included in this study. All examinations were performed on 1.5 Tesla MRI systems. Visual evaluations of the colored perfusion map and MRI perfusion values were assessed. MRI and computed tomography (CT) perfusion values were compared. RESULTS: Thirteen of 14 tumor lesions could be visualized on the colored perfusion map. CT perfusion examinations were performed in eight breasts, and the relationship between the blood flow values of CT perfusion and of MR perfusion showed a significant correlation. CONCLUSION: Nonenhanced MR imaging by an ASL technique is valid for depicting breast cancer, and the MR perfusion value is thought to be helpful for quantitative diagnosis of breast cancer. PMID- 22095486 TI - Cell-free collagen type I matrix for repair of cartilage defects-clinical and magnetic resonance imaging results. AB - PURPOSE: Several well-described techniques are available for the treatment of chondral and osteochondral defects. The aim of the study was to assess the efficacy of a single-stage procedure incorporating a new cell-free collagen type I gel for the treatment of small chondral and osteochondral defects in the knee evaluated at 2-year follow-up. METHODS: Fifteen patients were treated with a cell free collagen type I gel matrix of 11 mm diameter. The grafts were implanted in the debrided cartilage defect and fixed by press-fit only. The clinical outcome was assessed preoperatively and at 6 weeks, and 6, 12 and 24 months after surgery using the International Knee Documentation Committee (IKDC) score, Tegner activity scale and visual analogue scale (VAS). Graft attachment rate was assessed 6 weeks postoperatively using magnetic resonance imaging (MRI). Cartilage regeneration was evaluated using the Magnetic Observation of Cartilage Repair Tissue (MOCART) score at 6, 12 and 24 months after implantation. Clinical results were correlated with MRI findings. RESULTS: Six male and nine female patients were included in this study, with a mean age of 26 (range: 19-40). No complications were reported. The mean VAS values after 6 weeks and the mean IKDC patient values after 6 months were significantly improved from the preoperative values (P = 0.005 and P = 0.009, respectively). This improvement remained up to the latest follow-up. There were no significant differences between the median preoperative and postoperative Tegner values (n.s.). Significant improvement of the mean MOCART score was observed after 12 months and remained by 24 months (P < 0.001). MR images showed that in 14 of the 15 patients, the graft was completely attached by 6 weeks postoperatively. At 24 months after implantation, MRI demonstrated complete filling in all cases with a mainly smooth surface, complete integration of the border zone, homogenous structure of the repaired tissue and nearly normal signal intensity. No correlation between any variables of the MOCART score and the clinical scores was observed. CONCLUSIONS: The present study reveals that the new method produces both good clinical and magnetic resonance imaging results. Use of press-fit only implanted grafts of a smaller diameter leads to a high attachment rate at 24-month follow-up. LEVEL OF EVIDENCE: IV. PMID- 22095488 TI - Early protective effect of mitofusion 2 overexpression in STZ-induced diabetic rat kidney. AB - Diabetic nephropathy (DN) is a serious complication of diabetes with a poorly defined etiology and limited treatment options. Early intervention is key to preventing the progression of DN. Mitofusin 2 (Mfn2) regulates mitochondrial morphology and signaling, and is involved in the pathogenesis of numerous diseases. Furthermore, Mfn2 is also closely associated with the development of diabetes, but its functional roles in the diabetic kidney remain unknown. This study investigated the effect of Mfn2 at an early stage of DN. Mfn2 was overexpressed by adenovirus-mediated gene transfer in streptozotocin-induced diabetic rats. Clinical parameters (proteinuria, albumin/creatinine ratio), pathological changes, ultra-microstructural changes in nephrons, expression of collagen IV and phosph-p38, ROS production, mitochondrial function, and apoptosis were evaluated and compared with diabetic rats expressing control levels of Mfn2. Endogenous Mfn2 expression decreased with time in DN. Compared to the blank transfection control group, overexpression of Mfn2 decreased kidney weight relative to body weight, reduced proteinuria and ACR, and improved pathological changes typical of the diabetic kidney, like enlargement of glomeruli, accumulation of ECM, and thickening of the basement membrane. In addition, Mfn2 overexpression inhibited activation of p38, and the accumulation of ROS; prevented mitochondrial dysfunction; and reduced the synthesis of collagen IV, but did not affect apoptosis of kidney cells. This study demonstrates that Mfn2 overexpression can attenuate pathological changes in the kidneys of diabetic rats. Further studies are needed to clarify the underlying mechanism of this protective function. Mfn2 might be a potential therapeutic target for the treatment of early stage DN. PMID- 22095489 TI - A rare S33C mutation of CTNNB1 encoding beta-catenin in a parathyroid adenoma found in an Italian primary hyperparathyroid cohort. PMID- 22095490 TI - Relationship of age to bone microstructure independent of areal bone mineral density. AB - Previous studies using dual-energy X-ray absorptiometry (DXA) have demonstrated that age is a major predictor of bone fragility and fracture risk independent of areal bone mineral density (aBMD). Although this aBMD-independent effect of age has been attributed to poor bone "quality," the structural basis for this remains unclear. Because high-resolution peripheral quantitative computed tomography (HRpQCT) can assess bone microarchitecture, we matched younger and older subjects for aBMD at the ultradistal radius and assessed for possible differences in trabecular or cortical microstructure by HRpQCT. From an age-stratified, random sample of community adults, 44 women aged <50 years (mean age 41.0 years) were matched to 44 women aged >=50 years (mean age 62.7 years) by ultradistal radius aBMD (mean +/- SEM, younger and older aBMD 0.475 +/- 0.011 and 0.472 +/- 0.011 g/cm2, respectively), and 57 men aged <50 years (mean age 41.3 years) were matched to 57 men aged >=50 years (mean age 68.1 years; younger and older aBMD both 0.571 +/- 0.008 g/cm2). In these matched subjects, there were no sex specific differences in trabecular microstructural parameters. However, significant differences were noted in cortical microstructure (all p < 0.05): Older women and men had increased cortical porosity (by 91% and 56%, respectively), total cortical pore volume (by 77% and 61%, respectively), and mean cortical pore diameter (by 9% and 8%, respectively) compared with younger subjects. These findings indicate that younger and older women and men matched for DXA aBMD have similar trabecular microarchitecture but clearly different cortical microstructure, at least at an appendicular site represented by the radius. Further studies are needed to define the extent to which this deterioration in cortical microstructure contributes to the aBMD-independent effect of age on bone fragility and fracture risk at the distal radius and other sites of osteoporotic fractures. PMID- 22095492 TI - Precision profiling and identification of human serum peptides using Fourier transform ion cyclotron resonance mass spectrometry. AB - Many biomarker discovery studies are based on matrix-assisted laser desorption/ionisation (MALDI) peptide profiles. In this study, 96 human serum samples were analysed on a Bruker solariX(TM) MALDI Fourier transform ion cyclotron resonance (FTICR) system equipped with a 15 tesla magnet. Isotopically resolved peptides were observed in ultrahigh resolution FTICR profiles up to m/z 6500 with mass measurement errors (MMEs) of previously identified peptides at a sub-ppm level. For comparison with our previous platform for peptide profile mass analysis (i.e. Ultraflex II) the corresponding time-of-flight (TOF) spectra were obtained with isotopically resolved peptides up to m/z 3500. The FTICR and TOF systems performed rather similar with respect to the repeatability of the signal intensities. However, the mass measurement precision improved at least 10-fold in ultrahigh resolution data and thus simplified spectral alignment necessary for robust and quantitatively precise comparisons of profiles in large-scale clinical studies. From each single MALDI-FTICR spectrum an m/z-list was obtained with sub ppm precision for all different species, which is beneficial for identification purposes and interlaboratory comparisons. Furthermore, the FTICR system allowed new peptide identifications from collision-induced dissociation (CID) spectra using direct infusion of reversed-phase (RP) C(18)-fractionated serum samples on an electrospray ionisation (ESI) source. PMID- 22095493 TI - Thermodynamic study of gaseous vanadium phosphates by high-temperature mass spectrometry. AB - Knowledge of the structures of gaseous oxyacid salts of the M(m) XO(n) type is of interest for understanding the nature of chemical bonds. Gaseous VPO(2) and VPO(3) have been identified by Knudsen effusion mass spectrometry during the vaporization of mixtures of V(2)O(3) and alkali earth phosphates from molybdenum and tungsten effusion cells. The structures and molecular parameters of the gaseous vanadium phosphates under study were determined using quantum chemical calculations. On the basis of equilibrium constants measured for gas-phase reactions, the standard formation enthalpies were determined to be -273 +/- 17 and -615 +/- 16 kJ.mol(-1) for VPO(2) and VPO(3), respectively. PMID- 22095494 TI - Measurements of water vapor isotope ratios with wavelength-scanned cavity ring down spectroscopy technology: new insights and important caveats for deuterium excess measurements in tropical areas in comparison with isotope-ratio mass spectrometry. AB - The new infrared laser spectroscopic techniques enable us to measure the isotopic composition (delta(18)O and delta(2)H) of atmospheric water vapor. With the objective of monitoring the isotopic composition of tropical water vapor (West Africa, South America), and to discuss deuterium excess variability (d=delta(2)H 8delta(18)O) with an accuracy similar to measurements arising from isotope-ratio mass spectrometry (IRMS), we have conducted a number of tests and calibrations using a wavelength-scanned cavity ring-down spectroscopy (WS-CRDS) technique. We focus in this paper on four main aspects regarding (1) the tubing material, (2) the humidity calibration of the instrument, (3) the water vapor concentration effects on delta, and (4) the isotopic calibration of the instrument. First, we show that Synflex tubing strongly affects delta(2)H measurements and thus leads to unusable d values. Second, we show that the mixing ratio as measured by WS CRDS has to be calibrated versus atmospheric mixing ratio measurements and we also suggest possible non-linear effects over the whole mixing ratio range (~2 to 20 g/kg). Third, we show that significant non-linear effects are induced by water vapor concentration variations on delta measurements, especially for mixing ratios lower than ~5 g/kg. This effect induces a 5 to 100/00 error in deuterium excess and is instrument-dependent. Finally, we show that an isotopic calibration (comparison between measured and true values of isotopic water standards) is needed to avoid errors on deuterium excess that can attain ~100/00. PMID- 22095495 TI - Development of a simultaneous liquid chromatography/tandem mass spectrometric method for the determination of type B trichothecenes, their derivatives, and precursors in wheat. AB - A method coupling liquid chromatography with tandem mass spectrometry (LC/MS/MS) was developed for the simultaneous quantitative determination of trichothecenes, nivalenol, deoxynivalenol, deoxynivalenol-3-glucoside, fusarenon-X, 3 acetyldeoxynivalenol, 15-acetyldeoxynivalenol, isotrichodermin, calonectrin, 3 deacetylcalonectrin, 15-deacetylcalonectrin, 3,15-diacetylnivalenol, 4,15 diacetylnivalenol, 3,15-diacetyldeoxynivalenol, and 3,4,15-triacetylnivalenol. The analytical parameters of trichothecenes and their derivatives were optimized to enable their highly sensitive detection. Evaluation of clean-up procedures using Multisep #226 and #227 indicated that Multisep #227 was more suitable for their simultaneous detection in wheat. In performance validation studies using the LC/MS/MS method with Multisep #227 cleanup, good recoveries ranging from 84% to 115% with relative standard deviations from 0.4% to 7.2% were measured. The limits of detection and quantification ranged from 0.03 to 1.4 ng.g(-1) and from 0.1 to 4.7 ng.g(-1) , respectively. The effect of matrices using matrix-matched calibration was estimated to range from 80% to 117% after Multisep #227 cleanup. Multisep #227 clean-up procedure with matrix-free standard calibration achieved accurate quantification without having a considerable effect on matrix compounds. Using the developed method, several trichothecene derivatives and precursors were detected in fungally inoculated wheat samples. The developed LC/MS/MS method is a practical technique that can be used for the quantification of trichothecenes in wheat. This study is the first report of an analytical method used for the simultaneous quantification of major trichothecenes, their derivatives and precursors. PMID- 22095496 TI - Estimating lean mass over a wide range of body composition: a calibration of deuterium dilution in the arctic ground squirrel. AB - Calculating body water through isotope dilution has become a useful way to nondestructively estimate body composition in many species. The most accurate estimates using this method require calibration against proximate chemical analysis of body composition for individual species, but no studies to our knowledge have calibrated this method on a hibernating mammal that seasonally undergoes dramatic changes in body composition. We use deuterium oxide to estimate total body water in captive arctic ground squirrels, Urocitellus parryii, and compare two approaches of calculating lean mass from total body water, both calibrated against lean mass based on proximate analysis. The first method uses a single tissue hydration constant to calculate lean mass from total body water; the second method uses a predictive equation to calculate lean mass from total body water and body mass. We found that the predictive equation performs better over the large range of body composition common to this species. Distillation of blood samples did not affect lean mass estimates from either calculation method. These findings indicate that isotope dilution using a predictive equation should work well as an alternative to destructive methods in other small mammals that undergo radical changes in body composition across their annual cycle. PMID- 22095497 TI - Product ion mobility as a promising tool for assignment of positional isomers of drug metabolites. AB - Travelling wave ion mobility spectrometry - mass spectrometry (TWIMS-MS) was evaluated as a tool for structural identification of metabolites of small molecule drugs in cases where the exact position of the biotransformation could not be identified by conventional tandem mass spectrometry. Test sets of compounds containing biotransformations at aromatic positions were analyzed. These present a problem for traditional MS methods since an atomic level localization of the biotransformation cannot normally be determined from MS(n) spectra. In addition to ion mobility measurements of the intact metabolite ions, ion mobility measurements of product ions were also made and the results compared with calculated values. This approach reduces the complexity of the problem, making theoretical calculations easier and more predictable when a modeled collision cross section (CCS) is required. A good relative correspondence between theoretical and measured CCSs was obtained allowing the identification of the exact position of the biotransformation. It was also demonstrated that authentic standards with substructures identical to those in the unknown can be used to assign the exact position of the biotransformation. In this approach the identification was based on the comparison of the drift times or CCSs for product ions of the standard, with those of the same product ions in the unknown. PMID- 22095498 TI - Formation of tungstate-containing cluster ions by polyoxotungstate anions under matrix-assisted laser desorption/ionization conditions in the gas phase. AB - The gas-phase studies of transition-metal oxides continue to attract interest as such oxides are being used as catalysts in various oxidation processes. In this paper, singly negatively charged heteropolyoxotungstate and isopolyoxotungstate ion clusters were produced from Keggin-type polyoxotungstates by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). It was found that the ion series [(PO(3))(WO(3))(n)](-), [(WO(3))(n)](-) and [(OH)(WO(3))(n)](-) were the main fragment ions in the mass spectra and the matrix greatly influenced the resulting cluster ion abundances. [(PO(3))(WO(3))(3)](-), [(WO(3))(3)](-) and [(OH)(WO(3))(4)](-) were the most intense ions in each series when 2-(4 hydroxyphenylazo)benzoic acid was the matrix, whereas [(PO(3))(WO(3))(4)](-), [(WO(3))(6)](-) and [(OH)(WO(3))(4)](-) were the most intense when dithranol (DIT) was the matrix. In addition, a new kind of hybrid ion [W(2)C(14)H(7)O(8)]( ) was produced through the reaction of DIT and [(OH)(WO(3))](-) in the plume of the gas phase. These results highlight the utility of the MALDI-FT method for obtaining novel ion clusters and also show the stability of these clusters. PMID- 22095499 TI - Space-charge effects with mass-selective axial ejection from a linear quadrupole ion trap. AB - Methods to reduce mass shifts caused by space charge with mass-selective axial ejection from a linear quadrupole ion trap are investigated. For axial ejection, dipole excitation is applied to excite ions at q ~ 0.85. The trapping radiofrequency (rf) voltage is scanned to bring ions of different m/z values into resonance for excitation. In the fringing field at the quadrupole exit, excited ions gain axial kinetic energy, overcoming the trapping potential, and are ejected from the trap. Space charge causes the frequencies of ion oscillation to decrease. Thus, greater rf voltages are required to bring ions into resonance for excitation and ejection, and the ions shift to higher apparent masses in a mass spectrum. At the same time, the peaks broaden, lowering resolution. The effects of injection q value, ejection q value, excitation amplitude, quadrupole dc voltages applied to the electrodes, applying an rf voltage to the exit lens, and scan speed, on mass shifts have been studied experimentally. Most experiments were done with only ions of protonated reserpine (m/z 609.3 and its isotopic peaks) in the trap. Some experiments were done with ions of protonated reserpine and ions of m/z 622 in the trap. In general, the mass shifts are reduced with higher ejection q values, higher excitation amplitudes, with quadrupole dc applied, and at higher scan speeds. The application of quadrupole dc appears to increase the ion cloud temperature, which lowers mass shifts. Thus, a proper choice of operating conditions can reduce, but not eliminate, mass shifts caused by space charge. PMID- 22095500 TI - Direct antigen detection from immunoprecipitated beads using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; a new method for immunobeads-mass spectrometry (iMS). AB - One-step detection of biological molecules is one of the principal techniques for clinical diagnosis, and the potential of mass spectrometry for biomarker detection has been a promising new approach in the field of medical sciences. We demonstrate here a new and high-sensitivity method that we termed immunobeads mass spectrometry (iMS), which combines conventional immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The key feature of iMS is the MS-compatible condition of immunoprecipitation using detergents with a monosaccaride-C8 alkyl chain or a disaccharide-C10 alkyl chain, and the minimized number of steps required for high sensitivity detection of target peptides in serum or biological fluid. This was achieved by optimizing the wash buffer and subjecting the immunobeads directly to MALDI-TOF MS analysis. Using this method, we showed that 1 fmol of amyloid beta peptide spiked in serum was readily detectable, demonstrating the powerful tool of iMS as a biomarker detection method. PMID- 22095502 TI - Can collision-induced negative-ion fragmentations of [M-H](-) anions be used to identify phosphorylation sites in peptides? AB - A joint experimental and theoretical investigation of the fragmentation behaviour of energised [M-H](-) anions from selected phosphorylated peptides has confirmed some of the most complex rearrangement processes yet to be reported for peptide negative ions. In particular: pSer and pThr (like pTyr) may transfer phosphate groups to C-terminal carboxyl anions and to the carboxyl anion side chains of Asp and Glu, and characteristic nucleophilic/cleavage reactions accompany or follow these rearrangements. pTyr may transfer phosphate to the side chains of Ser and Thr. The reverse reaction, namely transfer of a phosphate group from pSer or pThr to Tyr, is energetically unfavourable in comparison. pSer can transfer phosphate to a non-phosphorylated Ser. The non-rearranged [M-H](-) species yields more abundant product anions than its rearranged counterpart. If a peptide containing any or all of Ser, Thr and Tyr is not completely phosphorylated, negative-ion cleavages can determine the number of phosphated residues, and normally the positions of Ser, Thr and Tyr, but not which specific residues are phosphorylated. This is in accord with comments made earlier by Lehmann and coworkers. PMID- 22095501 TI - Global optimization of the infrared matrix-assisted laser desorption electrospray ionization (IR MALDESI) source for mass spectrometry using statistical design of experiments. AB - Design of experiments (DOE) is a systematic and cost-effective approach to system optimization by which the effects of multiple parameters and parameter interactions on a given response can be measured in few experiments. Herein, we describe the use of statistical DOE to improve a few of the analytical figures of merit of the infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source for mass spectrometry. In a typical experiment, bovine cytochrome c was ionized via electrospray, and equine cytochrome c was desorbed and ionized by IR-MALDESI such that the ratio of equine:bovine was used as a measure of the ionization efficiency of IR-MALDESI. This response was used to rank the importance of seven source parameters including flow rate, laser fluence, laser repetition rate, ESI emitter to mass spectrometer inlet distance, sample stage height, sample plate voltage, and the sample to mass spectrometer inlet distance. A screening fractional factorial DOE was conducted to designate which of the seven parameters induced the greatest amount of change in the response. These important parameters (flow rate, stage height, sample to mass spectrometer inlet distance, and laser fluence) were then studied at higher resolution using a full factorial DOE to obtain the globally optimized combination of parameter settings. The optimum combination of settings was then compared with our previously determined settings to quantify the degree of improvement in detection limit. The limit of detection for the optimized conditions was approximately 10 attomoles compared with 100 femtomoles for the previous settings, which corresponds to a four orders of magnitude improvement in the detection limit of equine cytochrome c. PMID- 22095503 TI - Continuous-flow step gradient mass spectrometry based method for the determination of kinetic parameters of immobilized mushroom tyrosinase in equilibrating conditions: comparison with free enzyme. AB - A mass spectrometry (MS)-based methodology for enzymatic assay in equilibrium conditions was designed and evaluated. This on-line assay involves the introduction of a continuous-flow step gradient (CFSG) of a substrate solution in the column containing immobilized enzyme and the simultaneous tracking of the product formation. We showed that the constant concentration of substrate in the entire bioreactor for an appropriate duration ensures the equilibration of the studied enzyme (mushroom tyrosinase). Under these conditions, it was demonstrated also that the kinetic and enzymatic parameters (Michaelis-Menten constant, K(M) , the maximal specific activity, SA(max)) are independent of the flow rate of the mobile phase. The feasibility of the mentioned approach for inhibitory tests was also investigated. The coupling of the mass spectrometer to the bio-reactor allows the selective monitoring of the enzymatic reaction products and increases their detection level. Very high sensitivity, 500 pmol/min/column, and selective monitoring of the products of the enzymatic reaction are allowed by MS detection. The methodology developed here constitutes a sensitive analytical tool to study enzymes requiring long equilibration times. PMID- 22095505 TI - Systematic fragmentation patterns of archaeal intact polar lipids by high performance liquid chromatography/electrospray ionization ion-trap mass spectrometry. AB - Archaea are ubiquitous and abundant microorganisms on Earth that mediate key global biogeochemical cycles. The headgroup attached to the sn-1 position of the glycerol backbone and the ether-linked isoprenoid lipids are among the diagnostic traits that distinguish Archaea from Bacteria and Eukarya. Over the last 30 years, numerous archaeal lipids have been purified and described in pure cultures. Coupled high-performance liquid chromatography (HPLC) ion-trap mass spectrometry (ITMS) now enables the detection and rapid identification of intact polar lipids in relatively small and complex samples, revealing a wide range of archaeal lipids in natural environments. Although major structural groups have been identified, the lack of a systematic evaluation of MS/MS fragmentation patterns has hindered the characterization of several atypical components that are therefore considered as unknowns. Here, we examined mass spectra resulting from lipid analysis of natural microbial communities using HPLC/electrospray ionization (ESI)-ITMS(n), and depicted the systematics in MS(2) fragmentation of intact archaeal lipids. This report will be particularly useful for environmental scientists interested in a rapid and straightforward characterization of intact archaeal membrane lipids. PMID- 22095504 TI - Mammalian DNA delta15N exhibits 400/00 intramolecular variation and is unresponsive to dietary protein level. AB - We report the first high-precision characterization of molecular and intramolecular delta(15)N of nucleosides derived from mammalian DNA. The influence of dietary protein level on brain amino acids and deoxyribonucleosides was determined to investigate whether high protein turnover would alter amino acid (15)N or (13)C values. Pregnant guinea pig dams were fed control diets, or high or low levels of dietary protein throughout gestation, and all pups were fed control diets. The cerebellar DNA of offspring was extracted at 2 and 120 days of life, nucleosides isolated and delta(15)N and delta(13)C values characterized. Mean diet delta(15)N was 0.45 +/- 0.330/00, compared with cerebellar whole tissue and DNA delta(15) N= +4.1 +/- 0.70/00 and -4.5 +/- 0.40/00, respectively. Cerebellar deoxythymidine (dT), deoxycytidine (dC), deoxyadenosine (dA), and deoxyguanosine (dG) delta(15)N were +1.4 +/- 0.4, -2.1 +/- 0.9, -7.2 +/- 0.3, and -10.4 +/- 0.50/00, respectively. There were no changes in amino acid or deoxyribonucleoside delta(15) N values due to dietary protein level. Using known metabolic relationships, we developed equations to calculate the intramolecular delta(15)N values originating from aspartate (asp) in purines (pur) or pyrimidines (pyr), glutamine (glu), and glycine (gly) to be delta(15)N(ASP-PUR), delta(15)N(ASP-PYR), delta(15) N(GLN), and delta(15) N(GLY) +11.9 +/- 2.30/00, +7.0 +/- 2.00/00, -9.1 +/- 2.40/00, and -31.8 +/- 8.90/00, respectively. A subset of twelve amino acids from food and brain had mean delta(15) N values of 4.3 +/- 3.20/00 and 13.8 +/- 3.10/00, respectively, and delta(15)N values for gly and asp were 12.6 +/- 2.20/00 and 15.2 +/- 0.80/00, respectively. A separate isotope tracer study detected no significant turnover of cerebellar DNA in the first six months of life. The large negative delta(15)N difference between gly and cerebellar purine N at the gly (7) position implies either that there is a major isotope effect during DNA synthesis, or that in utero gly has a different isotope ratio during rapid growth and metabolism from that in adult life. Our data show that cerebellar nucleoside intramolecular delta(15)N values vary over more than 400/00 and are not influenced by dietary protein level or age. PMID- 22095506 TI - Evaluation of direct analysis in real time mass spectrometry for onsite monitoring of batch slurry reactions. AB - Batch slurry reactions are widely used in the industrial manufacturing of chemicals, pharmaceuticals, petrochemicals and polymers. However, onsite monitoring of batch slurry reactions is still not feasible in production plants due to the challenge in analyzing heterogeneous samples without complicated sample preparation procedures. In this study, direct analysis in real time mass spectrometry (DART-MS) has been evaluated for the onsite monitoring of a model batch slurry reaction. The results suggested that automation of the sampling process of DART-MS is important to achieve quantitative results. With a sampling technique of manual sample deposition on melting point capillaries followed by automatic sample introduction across the helium beam, relative standard deviation (RSD) of the protonated molecule signals from the reaction product of the model batch slurry reaction ranged from 6 to 30%. This RSD range is improved greatly over a sampling technique of manual sample deposition followed by manual sample introduction where the RSDs are up to 110%. Furthermore, with the semi-automated sampling approach, semi-quantitative analysis of slurry samples has been achieved. Better quantification is expected with a fully automated sampling approach. PMID- 22095507 TI - Characterization of diazeniumdiolate nitric oxide donors (NONOates) by electrospray ionization mass spectrometry. AB - Diazeniumdiolates (also called NONOates) have been analyzed by electrospray ionization mass spectrometry (ESI-MS). The samples used are commercially available and included Diethylamine NONOate, DETA NONOate, Spermine NONOate, MAHMA NONOate, PROLI NONOate, Dipropylenetriamine NONOate, PAPA NONOate, and Sulpho NONOate. These compounds have been found to ionize upon ESI by protonation, deprotonation and sodiation. The MS(n) experiments provided strong evidence that such ions release NO, HNO, N(2)O, NO(2), N(2)O(2), N(3)O(3), N(4)O(3) and N(4)O(4) when collisionally activated. Thus, the facile donation of NO units is a property of such compounds. Negative-mode mass spectrometry has been particularly useful for the analysis of most of the NONOates studied here. The experiments have demonstrated the capabilities of mass spectrometry, along with CAD (MS/MS), to detect and characterize such compounds. PMID- 22095508 TI - Liquid extraction surface analysis mass spectrometry (LESA-MS) as a novel profiling tool for drug distribution and metabolism analysis: the terfenadine example. AB - Liquid extraction surface analysis mass spectrometry (LESA-MS) is a novel surface profiling technique that combines micro-liquid extraction from a solid surface with nano-electrospray mass spectrometry. One potential application is the examination of the distribution of drugs and their metabolites by analyzing ex vivo tissue sections, an area where quantitative whole body autoradiography (QWBA) is traditionally employed. However, QWBA relies on the use of radiolabeled drugs and is limited to total radioactivity measured whereas LESA-MS can provide drug- and metabolite-specific distribution information. Here, we evaluate LESA MS, examining the distribution and biotransformation of unlabeled terfenadine in mice and compare our findings to QWBA, whole tissue LC/MS/MS and MALDI-MSI. The spatial resolution of LESA-MS can be optimized to ca. 1 mm on tissues such as brain, liver and kidney, also enabling drug profiling within a single organ. LESA MS can readily identify the biotransformation of terfenadine to its major, active metabolite fexofenadine. Relative quantification can confirm the rapid absorption of terfendine after oral dosage, its extensive first pass metabolism and the distribution of both compounds into systemic tissues such as muscle, spleen and kidney. The elimination appears to be consistent with biliary excretion and only trace levels of fexofenadine could be confirmed in brain. We found LESA-MS to be more informative in terms of drug distribution than a comparable MALDI-MS imaging study, likely due to its favorable overall sensitivity due to the larger surface area sampled. LESA-MS appears to be a useful new profiling tool for examining the distribution of drugs and their metabolites in tissue sections. PMID- 22095509 TI - Peptide polarity and the position of arginine as sources of selectivity during positive electrospray ionisation mass spectrometry. AB - Electrospray ionisation (ESI) is a selective process and, for similar sized analytes, the intrinsic properties of the molecules affect the ionisation process and their response. This research sets out to determine the effect of some of these properties in peptides: peptide polarity and the presence of arginine at positions 1 and 4 in the amino acid sequence on the ESI response. Six peptides; molecular mass ranges 1.3-1.6 kDa; substance P (SP) and glutamate fibrinopeptide (GFP) and 3.2-3.7 kDa; calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), glucagon-like peptide 1 (GLP1) and defensin human neutropeptide 2 (DHNP2), were investigated. We have demonstrated that in positive ESI, for similar sized peptides and the same charge state, the responsiveness is in the order: Peptides with N or C terminal arginine > most non-polar peptides > least non-polar peptides. Therefore, arginine at the terminal position is a source of selectivity. Data from matrix-assisted laser desorption ionisation (MALDI) analysis supports that of the ESI experiments: Peptides with a terminal arginine residue generated higher signal intensities. Our observations extend our understanding of the ESI process and provide a rational approach to optimising sensitivity of electrospray conditions where a narrow mass range of peptides are poorly chromatographically resolved. This information will provide for a more effective method development process, especially during label-free quantitative determination of peptides extracted in solution. PMID- 22095510 TI - Removal of 3'-phosphate group by bacterial alkaline phosphatase improves oligonucleotide sequence coverage of RNase digestion products analyzed by collision-induced dissociation mass spectrometry. AB - RNase mapping by nucleobase-specific endonucleases combined with liquid chromatography/tandem mass spectrometry (LC/MS/MS) is a powerful analytical method for characterizing ribonucleic acids (RNAs). Endonuclease digestion of RNA yields products that contain a 3'-terminal phosphate group. MS/MS via collision induced dissociation (CID) of these digestion products on a linear ion trap generates fragmentation pathways that include the loss of phosphoric acid ( H(3)PO(4); -98 u), which does not provide information about the sequence of the digestion products and can reduce ion abundance from other pathways that provide sequence information. Here we investigate the use of bacterial alkaline phosphatase (BAP) after RNase digestion to remove the 3'-terminal phosphate from all RNase digestion products prior to LC/MS/MS analysis. RNase digestion products lacking the 3'-phosphate were found to produce CID spectra with more consistent, high-abundance c- and y-type fragment ions as well as significantly more a-Base and w-type ions than digestion products retaining the 3'-phosphate. In this manner, RNase mapping with LC/MS/MS can provide more complete RNA sequence information from fragment ions of higher abundance that are easier to interpret and identify. PMID- 22095511 TI - An algorithm for identifying multiply modified endogenous proteins using both full-scan and high-resolution tandem mass spectrometric data. AB - Mass spectrometry based proteomic experiments have advanced considerably over the past decade with high-resolution and mass accuracy tandem mass spectrometry (MS/MS) capabilities now allowing routine interrogation of large peptides and proteins. Often a major bottleneck to 'top-down' proteomics, however, is the ability to identify and characterize the complex peptides or proteins based on the acquired high-resolution MS/MS spectra. For biological samples containing proteins with multiple unpredicted processing events, unsupervised identifications can be particularly challenging. Described here is a newly created search algorithm (MAR) designed for the identification of experimentally detected peptides or proteins. This algorithm relies only on predefined list of 'differential' modifications (e.g. phosphorylation) and a FASTA-formatted protein database, and is not constrained to full-length proteins for identification. The algorithm is further powered by the ability to leverage identified mass differences between chromatographically separated ions within full-scan MS spectra to automatically generate a list of likely 'differential' modifications to be searched. The utility of the algorithm is demonstrated with the identification of 54 unique polypeptides from human apolipoprotein enriched from the high-density lipoprotein particle (HDL), and searching time benchmarks demonstrate scalability (12 high-resolution MS/MS scans searched per minute with modifications considered). This parallelizable algorithm provides an additional solution for converting high-quality MS/MS data of multiply processed proteins into reliable identifications. PMID- 22095512 TI - Preliminary study for rapid determination of phycotoxins in microalgae whole cells using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. AB - Rapid and sensitive methods for identification of several phycotoxins produced by microalgae species such as yessotoxins (YTXs) for Protoceratium reticulatum, okadaic acid (OA) and pectenotoxins (PTXs) for Prorocentrum spp. and Dinophysis spp., Palytoxins (PLTXs) for Ostreopsis spp., ciguatoxins (CTXs) for Gambierdiscus spp. or domoic acid (DA) for Pseudo-nitzschia spp. are of great importance to the shellfish and fish industry. In this study, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was used to detect several phycotoxins in whole cells of some microalgae which are known as toxin producers. To achieve an appropriate MALDI matrix and a sample preparation method, several matrices and solvent mixtures were tested. The most appropriate matrix system for toxin detection was obtained with 10 ug MUL(-1) of DHB in 0.1% TFA/ACN (3:7, v/v) by mixing the intact cells with the matrix solution directly on the MALDI target (dried-droplet technique). Toxin detection by this procedure is much faster than current procedures based on solvent extraction and chromatographic separation. This method allowed the rapid detection of main phycotoxins in some dinoflagellate cells of genus Ostreopsis, Prorocentrum, Protoceratium, Gambierdiscus, Dinophysis and diatoms from Pseudo nitzschia genus. PMID- 22095513 TI - The effects of freeze/thaw periods and drying methods on isotopic and elemental carbon and nitrogen in marine organisms, raising questions on sample preparation. AB - Stable isotopes are an increasingly important tool in trophic linkage ecological studies. In studies of large marine animals, isotopic sampling is often given secondary priority to sampling for diversity and biomass aspects. Consequently, isotopic samples are frequently collected subsequent to repeated freezing and thawing of animals, and the results of these studies are often based on the assumption that this pre-treatment does not affect the isotopic values. Our study tested this assumption and examined the difference between oven- and freeze drying on isotopic values and elemental carbon-to-nitrogen (C:N) ratios. The values for delta(15)N and delta(13)C, percentage nitrogen and carbon, and the C:N ratios were determined from the tissues of six marine species, including invertebrates and fish, as (1) fresh samples, (2) samples thawed once, and (3) samples thawed twice. The drying method, thawing treatment and their interaction did significantly affect the delta(15)N and delta(13)C isotope values for all species. Oven-dried samples had slightly higher delta(13)C and delta(15)N values than freeze-dried samples, although not significant in most instances. For most species, oven-drying produced lower carbon and nitrogen percentage than freeze drying for samples that had been thawed once, but the C:N ratio was unaffected by the drying method. Repeated freezing and thawing did not affect the isotope values, but it did decrease the percentage carbon and nitrogen for both desiccation methods. We recommend drying samples from fresh wherever possible, and careful choice of desiccation method in light of the fact that most lipid models are based on oven-dried samples and oven-drying could cause enrichment of (15)N or (13)C through evaporation of volatile compounds richer in lighter isotopes such as some lipids. Finally, we recommend that further studies on the specific effects of freezing and desiccation on elasmobranchs is needed. Overall we recommend the use of freeze-drying when possible and to use the samples from freshly caught organisms. PMID- 22095514 TI - Structural determination of an unknown degradation product in posaconazole drug product using CASI technology in a Fourier transform ion cyclotron resonance mass spectrometer. PMID- 22095515 TI - Venom alkaloid and cuticular hydrocarbon profiles are associated with social organization, queen fertility status, and queen genotype in the fire ant Solenopsis invicta. AB - Queens in social insect colonies advertise their presence in the colony to: a) attract workers' attention and care; b) gain acceptance by workers as replacement or supplemental reproductives; c) prevent reproductive development in nestmates. We analyzed the chemical content of whole body surface extracts of adult queens of different developmental and reproductive stages, and of adult workers from monogyne (single colony queen) and polygyne (multiple colony queens) forms of the fire ant Solenopsis invicta. We found that the composition of the most abundant components, venom alkaloids, differed between queens and workers, as well as between reproductive and non-reproductive queens. Additionally, workers of the two forms could be distinguished by alkaloid composition. Finally, sexually mature, non-reproductive queens from polygyne colonies differed in their proportions of cis-piperidine alkaloids, depending on their Gp-9 genotype, although the difference disappeared once they became functional reproductives. Among the unsaturated cuticular hydrocarbons characteristic of queens, there were differences in amounts of alkenes/alkadienes between non-reproductive polygyne queens of different Gp-9 genotypes, between non-reproductive and reproductive queens, and between polygyne and monogyne reproductive queens, with the amounts increasing at a relatively higher rate through reproductive ontogeny in queens bearing the Gp-9 b allele. Given that the genotype-specific piperidine differences reflect differences in rates of reproductive maturation between queens, we speculate that these abundant and unique compounds have been co-opted to serve in fertility signaling, while the cuticular hydrocarbons now play a complementary role in regulation of social organization by signaling queen Gp-9 genotype. PMID- 22095516 TI - Clinical relevance of detectable but not quantifiable hepatitis C virus RNA during boceprevir or telaprevir treatment. AB - Boceprevir- and telaprevir-based treatments for chronic hepatitis C virus (HCV) infection use specific response-guided therapy (RGT) guidelines. Eligibility for shortened treatment duration is based on achieving undetectable HCV RNA early during treatment. It is unclear whether a detected HCV RNA level that is below the assay lower limit of quantitation (detectable/BLOQ) is comparable to an undetectable HCV RNA level for RGT decision making. We analyzed data from boceprevir and telaprevir clinical trials to obtain a comprehensive understanding of the frequency and clinical relevance of detectable/BLOQ HCV RNA measurements. In Phase 3 trials P05216 (boceprevir), C216 (telaprevir), and 108 (telaprevir), detectable/BLOQ levels were reported for approximately 10%-20% of all on treatment HCV RNA measurements. In P05216 and C216, subjects with detectable/BLOQ HCV RNA, on average, had a reduced sustained virologic response (SVR) rate compared with subjects with undetectable HCV RNA at the same on-treatment timepoint. At key RGT timepoints (week 8 for boceprevir, week 4 for telaprevir), subjects with detectable/BLOQ HCV RNA had an approximately 20% lower SVR rate compared with subjects with undetectable HCV RNA, and this difference widened for later on-treatment timepoints. A similar trend was observed for Study 108, but the differences in SVR rates were modest, potentially explained by a higher frequency of reported detectable/BLOQ results. Analyses of Phase 2 boceprevir and telaprevir trials indicated subjects with detectable/BLOQ HCV RNA at RGT timepoints benefited from extended treatment duration. CONCLUSION: During boceprevir- and telaprevir-based treatment, subjects with detectable/BLOQ HCV RNA had a reduced virologic response compared with subjects with undetectable HCV RNA. Eligibility for shortened treatment duration should be based on achieving undetectable HCV RNA (i.e., HCV RNA not detected) at RGT decision timepoints. PMID- 22095517 TI - Hexim-1 modulates androgen receptor and the TGF-beta signaling during the progression of prostate cancer. AB - BACKGROUND: Androgen and TGF-beta signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD: Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim-1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim-1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim-1 gene to generate TRAMP-C2-Hexim-1+/- cell lines. RESULTS: In this report, we observed that Hexim-1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim-1 gene in the prostate cancer mice model and the TRAMP-C2 cell line, leads to increased Cdk9-dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF beta-dependent downstream transcription factors, such as the SMAD proteins. CONCLUSION: Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF beta signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression. PMID- 22095518 TI - HIV-1 integrase inhibitors: a review of their chemical development. AB - Highly active antiretroviral therapy (HAART) significantly decreases plasma viral load, increases CD4+ T-cell counts in HIV-1-infected patients and has reduced progression to AIDS in developed countries. However, adverse side effects, and emergence of drug resistance, mean there is still a demand for new anti-HIV agents. The HIV integrase (IN) is a target that has been the focus of rational drug design over the past decade. In 2007, raltegravir was the first IN inhibitor approved by the US Food and Drug Administration for antiretroviral combination therapy, while another IN inhibitor, elvitegravir, is currently in Phase III clinical trials. This article reviews the development and resistance profiling of small molecule HIV-1 IN inhibitors. PMID- 22095519 TI - Mechanism of interaction of novel indolylarylsulfone derivatives with K103N and Y181I mutant HIV-1 reverse transcriptase in complex with its substrates. AB - BACKGROUND: Novel indolylarylsulfones (IASs), designed through rational structure based molecular modelling and docking approaches, have been recently characterized as effective inhibitors of the wild-type and drug-resistant mutant HIV-1 reverse transcriptase (RT). METHODS: Here, we studied the interaction of selected halo- and nitro-substituted IAS derivatives, with the RT enzyme carrying the single resistance mutations K103N and Y181I through steady-state kinetic experiments. RESULTS: The studied compounds exhibited high selectivity to the mutant RT in complex with its substrates, behaving as uncompetitive inhibitors. The presence of the K103N mutation, and to a lesser extent the Y181I, stabilized the drug interactions with the viral RT, when both its substrates were bound. CONCLUSIONS: The characterization of these mutation-specific effects on inhibitor binding might be relevant to the design of more effective new generation non nucleoside reverse transcriptase inhibitors, with better resilience towards drug resistant mutants. PMID- 22095520 TI - Inhibition of influenza virus replication by constrained peptides targeting nucleoprotein. AB - BACKGROUND: Because of high mutation rates, new drug-resistant viruses are rapidly evolving, thus making the necessary control of influenza virus infection difficult. METHODS: We screened a constrained cysteine-rich peptide library mimicking MU-conotoxins from Conus geographus and a proline-rich peptide library mimicking lebocin 1 and 2 from Bombyx mori by using influenza virus RNA polymerase (PB1, PB2 and PA) and nucleoprotein (NP) as baits. RESULTS: Among the 22 peptides selected from the libraries, we found that the NP-binding proline rich peptide, PPWCCCSPMKRASPPPAQSDLPATPKCPP, inhibited influenza replicon activity to mean+/-sd 40.7%+/-15.8% when expressed as a GFP fusion peptide in replicon cells. Moreover, when the GFP fusion peptide was transduced into cells by an HIV-TAT protein transduction domain sequence, the replication of influenza virus A/WSN/33 (WSN) at a multiplicity of infection of 0.01 was inhibited to 20% and 69% at 12 and 24 h post-infection, respectively. In addition, the TAT-GFP fusion peptide was able to slightly protect Balb/c mice from WSN infection when administrated prior to the infection. CONCLUSIONS: These results suggest the potential of this peptide as the seed of an anti-influenza drug and reveal the usefulness of the constrained peptide strategy for generating inhibitors of influenza infection. The results also suggest that influenza NP, which is conserved among the influenza A viruses, is a good target for influenza inhibition, despite being the most abundant protein in infected cells. PMID- 22095521 TI - Efficacy of orally administered low dose N-methanocarbathymidine against lethal herpes simplex virus type-2 infections of mice. AB - BACKGROUND: N-methanocarbathymidine (N-MCT) has previously been shown to be effective against lethal orthopoxvirus and herpes simplex virus type-1 infections in mice. In this investigation, the antiviral activity of N-MCT was assessed against herpes simplex virus type-2 (HSV-2) in BALB/c mice. METHODS: BALB/c mice were infected intranasally with a lethal challenge dose of HSV-2. N-MCT was administered orally twice daily to mice using doses of 0.01 to 100 mg/kg to determine effects on survival and on viral replication in organ and central nervous system (CNS) samples. RESULTS: N-MCT provided significant protection from mortality even when treatments were delayed until 3 days after viral infection. Viral replication in organ and CNS samples from N-MCT-treated mice was reduced below the limit of detection after 4 days of treatment. CONCLUSIONS: These results indicated that low dose N-MCT treatment was more effective than acyclovir therapy. N-MCT may be effective against HSV disease in humans and is currently undergoing preclinical evaluation. In particular, its potential use as a combination therapy for HSV, with its differing metabolism from acyclovir, make it a promising compound to develop for human use. PMID- 22095522 TI - Clinical significance of Zinc finger E-box Binding homeobox 1 (ZEB1) in human gastric cancer. AB - BACKGROUND AND OBJECTIVES: Zinc finger E-box Binding homeobox 1 (ZEB1) encodes a transcription factor and is one of the epithelial-mesenchymal transition (EMT) inducible genes that play a key role in tumor progression in various cancers. The aim of this study is to clarify the clinical significance of ZEB1 expression in gastric cancer patients. METHODS: One hundred thirty-four patients who underwent surgery for gastric cancer were evaluated. We analyzed ZEB1 mRNA levels by real time reverse transcription PCR in gastric cancer tissue and adjacent normal mucosa. ZEB1 protein expression in primary cancer and in peritoneal dissemination samples was measured using immunohistochemical analysis. RESULTS: Expression of the ZEB1 gene was significantly higher in cancerous tissue than in adjacent normal mucosa. Increased ZEB1 expression was significantly associated with peritoneal dissemination, and was an independent prognostic factor. Logistic regression analysis revealed that increased ZEB1 expression was an independent risk factor for peritoneal dissemination. Immunohistochemical analysis indicated that ZEB1 was intensely expressed in both primary cancer and peritoneal dissemination samples. CONCLUSIONS: ZEB1 is an independent factor for peritoneal dissemination in patients with gastric cancer, and may therefore play a key role in the progression to peritoneal dissemination in gastric cancer patients. PMID- 22095523 TI - High survival during hibernation affects onset and timing of reproduction. AB - The timing of reproduction is one of the most crucial life history traits, with enormous consequences for the fitness of an individual. We investigated the effects of season and timing of birth on local survival probability in a small mammalian hibernator, the common dormouse (Muscardinus avellanarius). Local monthly survival probability was lowest in the early active season (May-August, phi(adult) = 0.75-0.88, phi(juvenile) = 0.61-0.68), increased during the late active season (August-October), and highest during hibernation (October-May, phi(adult) = 0.96-0.98, phi(juvenile) = 0.81-0.94). Consequently, dormice had an extremely high winter survival probability. We observed two peaks in the timing of reproduction (June and August/September, respectively), with the majority of juveniles born late in the active season. Although early investment in reproduction seems the better life history tactic [survival probability until onset of reproduction: phi(born early) = 0.46, 95% confidence interval (CI) 0.28 0.64; phi(born late) = 0.19, 95% CI = 0.09-0.28], only females with a good body condition (significantly higher body mass) invest in reproduction early in the year. We suggest the high over-winter survival in dormice allows for a unique life history pattern (i.e., combining slow and fast life history tactics), which leads to a bimodal seasonal birth pattern: (1) give birth as early as possible to allow even the young to breed before hibernating, and/or (2) give birth as late as possible (leaving just enough time for these young to fatten) and enter directly into a period associated with the highest survival rates (hibernation) until maturity. PMID- 22095524 TI - Surgical resection versus local ablation for HCC on cirrhosis: results from a propensity case-matched study. AB - BACKGROUND: Surgery for hepatocellular carcinoma (HCC) had great improvements in the last decades with low morbidity and mortality and good long-term results. Percutaneous local ablative therapies (LAT) such as radiofrequency ablation and ethanol injection (PEI) for HCC gained consent for their efficacy and safety. In retrospective studies, patients submitted to resection (LR) or LAT frequently have important selection bias. Propensity case-matched analysis proved to reduce selection bias of retrospective studies and allow comparison between different therapies. AIM: The aim of this study was to evaluate survival comparing LR and LAT in two groups of cirrhotic patients with HCC matched with propensity score methods. METHODS: Four hundred and seventy-eight cirrhotic patients with HCC treated with LR or LAT with curative intent between January 1995 and December 2009 were included in the study. One hundred and eighty-one patients underwent LR, and 297 patients were treated with LAT. Tumor stage and liver function were evaluated in all patients. To balance the covariates in the two groups, a one-to one propensity case-matched analysis was used. A multivariable logistic model based on age, gender, etiology of cirrhosis, Child-Pugh class, number of nodules, maximum diameter of nodules, and serum alpha-fetoprotein level was used to estimate propensity score. One-to-one caliper matching of LR and LAT groups was performed, generating a matched sample of 176 patients with 88 patients in each group. RESULTS: Median survival was 65.1 months (95% CI = 48.5-81.7) after LR and 37.3 months (95% CI = 29.3-45.3) after LAT (p = 0.008). For patients in Child Pugh class A with single HCC and maximum diameter <5 cm, median survival was 65.0 months (95% CI = 58.4-71.6) for the LR group and 63.7 months (95% CI = 31.8-95.7) for the LAT group (p = 0.730). For patients in Child-Pugh class A with single HCC and diameter >=5 cm, median survival was 79.9 months (95% CI = 40.1-119.8) for the LR group and 21.5 months (95% CI = 10.8-32.1) for the LAT group (p = 0.023). For patients in Child-Pugh class A with two to three nodules and maximum diameter <=3 cm, mean survival was 69.3 months (95% CI 48.7-89.9) for the LR group and 45.7 months (95% CI = 22.8-68.7) for the LAT group (p = 0.168). For patients in Child-Pugh class A with two to three nodules and diameter >3 cm, median survival was 82.9 months (95% CI = 52.0-113.7) for the LR group and 18.9 months (95% CI = 6.3-31.4) for the LAT group (p = 0.001). CONCLUSION: Our propensity case-matched study confirmed that survival is similar after LR and LAT for single HCC smaller than 5 cm and for oligofocal HCC (up to three nodules) smaller than 3 cm; instead, for HCC larger than 5 cm or oligofocal HCC (up to three nodules) larger than 3 cm, surgical resection improves significantly long-term survival. PMID- 22095525 TI - Intraluminal pH and goblet cell density in Barrett's esophagus. AB - INTRODUCTION: Goblet cells in Barrett's esophagus (BE) vary in their density within the Barrett's segment. Exposure of Barrett's epithelium to bile acids is a major stimulant for goblet cell formation. The dissociation of bile acids into forms that penetrate Barrett's epithelium is known to be pH dependent. We hypothesized that variations in the esophageal luminal pH environment explains the variability in goblet cell density. The aim of this study was to correlate esophageal luminal pH with goblet cell density in patients with BE. METHODS: A customized six-sensor pH catheter was positioned with the most distal sensor in the stomach and the remaining sensors located 1 cm below and 1, 3, 5, and 8 cm above the upper border of the lower esophageal sphincter in five normal subjects and six patients with long-segment BE. The luminal pH was measured by each sensor for 24-h and expressed as median pH. Patients with BE had four quadrant biopsies at levels corresponding to the location of the pH sensors. Goblet cell density was graded from 0 to 3 based on the number per high-power field. RESULTS: In normal subjects, the median pH values recorded in the sensors within the lower esophageal sphincter (LES) and esophageal body were all above 5. In patients with BE, the median pH recorded by the sensor within the LES was 2.8 and increased progressively to 4.7 in the sensor at 8 cm above the LES. Goblet cell density was significantly lower in the distal Barrett's segment exposed to a median pH of 2.2 and increased in the proximal Barrett's segment exposed to a median pH of 4.4 (p = 0.003). CONCLUSION: Patients with BE have a goblet cell gradient that correlates directly with an esophageal luminal pH gradient. This suggests that goblet cell differentiation is pH dependent and likely due to the effect of pH on bile acid dissociation. PMID- 22095526 TI - The challenge of enzyme cost in the production of lignocellulosic biofuels. AB - With the aim of understanding the contribution of enzymes to the cost of lignocellulosic biofuels, we constructed a techno-economic model for the production of fungal cellulases. We found that the cost of producing enzymes was much higher than that commonly assumed in the literature. For example, the cost contribution of enzymes to ethanol produced by the conversion of corn stover was found to be $0.68/gal if the sugars in the biomass could be converted at maximum theoretical yields, and $1.47/gal if the yields were based on saccharification and fermentation yields that have been previously reported in the scientific literature. We performed a sensitivity analysis to study the effect of feedstock prices and fermentation times on the cost contribution of enzymes to ethanol price. We conclude that a significant effort is still required to lower the contribution of enzymes to biofuel production costs. PMID- 22095527 TI - Neutral nickel oligo- and polymerization catalysts: the importance of alkyl phosphine intermediates in chain termination. AB - An unconventional chain termination reaction has been explored for the SHOP (Shell higher olefin process)-type, anilinotropone, and salicylaldiminato nickel based oligo- and polymerization catalysts by using density functional theory (DFT). Starting from the tetracoordinate alkyl phosphine complex, the termination reaction was found to involve a rearrangement of the alkyl chain to form a pentacoordinate beta-agostic complex, beta-hydride elimination, and olefinic chain dissociation and to compete with propagation at sufficiently high phosphine concentration and/or basicity. It provides the first complete and convincing mechanistic rationale for the decreasing chain lengths observed upon increasing phosphine concentration and basicity. The unconventional reaction was found to be a major termination pathway for the SHOP-type catalyst and is very unlikely to lead to branching and olefin isomerization, which is critical for explaining why the SHOP catalyst, in contrast to the anilinotropone and salicylaldiminato catalysts, tends to lead to the oligomerization of ethylene to form linear alpha olefins. Based on our results we have proposed a new and extended catalytic cycle for the SHOP-type ethylene oligomerization catalyst. Finally, the importance of the new termination reaction for the SHOP-type catalyst suggests that this reaction may also operate with other ethylene oligomerization nickel catalysts. This prediction was confirmed for a pyrazolonatophosphine catalyst, for which the new termination route was found to be even more facile, which explains the short oligomers produced by this catalyst. PMID- 22095528 TI - Hypothalamic action of glutamate leads to body mass reduction through a mechanism partially dependent on JAK2. AB - Glutamate acts in the hypothalamus promoting region-, and cell-dependent effects on feeding. Part of these effects are mediated by NMDA receptors, which are up regulated in conditions known to promote increased food intake and thermogenesis, such as exposure to cold and consumption of highly caloric diets. Here, we hypothesized that at least part of the effect of glutamate on hypothalamic control of energy homeostasis would depend on the control of neurotransmitter expression and JAK2 signaling. The expression of NMDA receptors was co-localized to NPY/AgRP, POMC, CRH, and MCH but not to TRH and orexin neurons of the hypothalamus. The acute intracerebroventricular injection of glutamate promoted a dose-dependent increase in JAK2 tyrosine phosphorylation. In obese rats, 5 days intracerebroventricular treatment with glutamate resulted in the reduction of food intake, accompanied by a reduction of spontaneous motility and reduction of body mass, without affecting oxygen consumption. The reduction of food intake and body mass were partially restrained by the inhibition of JAK2. In addition, glutamate produced an increased hypothalamic expression of NPY, POMC, CART, MCH, orexin, CRH, and TRH, and the reduction of AgRP. All these effects on neurotransmitters were hindered by the inhibition of JAK2. Thus, the intracerebroventricular injection of glutamate results in the reduction of body mass through a mechanism, at least in part, dependent on JAK2, and on the broad regulation of neurotransmitter expression. These effects are not impaired by obesity, which suggest that glutamate actions in the hypothalamus may be pharmacologically explored to treat this disease. PMID- 22095529 TI - Resveratrol acts as a topoisomerase II poison in human glioma cells. AB - Recently, we demonstrated that Resveratrol (RSV), a well known natural stilbene, is able to induce a delay in S progression with a concomitant increase in gammaH2AX expression in U87 glioma cells. Furthermore, we showed that it inhibits the ability of recombinant human topoisomerase IIalpha to decatenate kDNA in vitro. Because proliferating tumor cells express topoisomerases at high levels and these enzymes are important targets of some of the most successful anticancer drugs, we tested whether RSV is able to poison topoisomerase IIalpha in glioma cells. Then, we monitored the increase of micronuclei in RSV treated U87 cells as a consequence of the conversion of TOPOII/DNA cleavable complexes to permanent DNA damage. Finally, we assayed the ability of RSV in modulating the expression of target proteins involved in DNA damage signalling, namely ATR, ATM, Chk1, Chk2 and gammaH2AX. Through a molecular modelling here we show that RSV binds at the TOPOII/DNA interface thus establishing several hydrogen bonds. Moreover, we show that RSV poisons TOPOIIalpha so inducing DNA damage; ATM, Chk2 and gammaH2AX are involved in the DNA damage signalling after RSV treatment. PMID- 22095530 TI - Baseline characteristics and statistical implications for the OECD 210 fish early life stage chronic toxicity test. AB - The fish toxicity assay most commonly used to establish chronic effects is the Organisation for Economic Co-operation and Development (OECD) 210, fish early life stage test. However, the authors are not aware of any systematic analysis of the experimental design or statistical characteristics of the test since the test guideline was adopted nearly 20 years ago. Here, the authors report the results of an analysis of data compiled from OECD 210 tests conducted by industry labs. The distribution of responses observed in control treatments was analyzed, with the goal of understanding the implication of this variability on the sensitivity of the OECD 210 test guideline and providing recommendations on revised experimental design requirements of the test. Studies were confined to fathead minnows, rainbow trout, and zebrafish. Dichotomous endpoints (hatching success and posthatch survival) were examined for indications of overdispersion to evaluate whether significant chamber-to-chamber variability was present. Dichotomous and continuous (length, wet wt, dry wt) measurement endpoints were analyzed to determine minimum sample size requirements to detect differences from control responses with specified power. Results of the analysis indicated that sensitivity of the test could be improved by maximizing the number of replicate chambers per treatment concentration, increasing the acceptable level of control hatching success and larval survival compared to current levels, using wet weight measurements rather than dry weight, and focusing test efforts on species that demonstrate less variability in outcome measures. From these analyses, the authors provide evidence of the impact of expected levels of variability on the sensitivity of traditional OECD 210 studies and the implications for defining a target for future animal alternative methods for chronic toxicity testing in fish. PMID- 22095531 TI - Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. AB - Craniorachischisis (CRN) is a severe neural tube defect (NTD) resulting from failure to initiate closure, leaving the hindbrain and spinal neural tube entirely open. Clues to the genetic basis of this condition come from several mouse models, which harbor mutations in core members of the planar cell polarity (PCP) signaling pathway. Previous studies of humans with CRN failed to identify mutations in the core PCP genes, VANGL1 and VANGL2. Here, we analyzed other key PCP genes: CELSR1, PRICKLE1, PTK7, and SCRIB, with the finding of eight potentially causative mutations in both CELSR1 and SCRIB. Functional effects of these unique or rare human variants were evaluated using known protein-protein interactions as well as subcellular protein localization. While protein interactions were not affected, variants from five of the 36 patients exhibited a profound alteration in subcellular protein localization, with diminution or abolition of trafficking to the plasma membrane. Comparable effects were seen in the crash and spin cycle mouse Celsr1 mutants, and the line-90 mouse Scrib mutant. We conclude that missense variants in CELSR1 and SCRIB may represent a cause of CRN in humans, as in mice, with defective PCP protein trafficking to the plasma membrane a likely pathogenic mechanism. PMID- 22095532 TI - Viral kinetics during the first weeks of pegylated interferon and ribavirin treatment can identify patients at risk of relapse after its discontinuation: new strategies for such patients? AB - BACKGROUND: Pegylated interferon (PEG-IFN) and ribavirin is the most effective treatment for chronic hepatitis C virus (HCV) hepatitis, but the rate of sustained virological response (SVR) remains approximately 50%, and 15-20% of all treated patients have a virological relapse after completing the treatment. Studies on the SVR have failed to discriminate between non-responders and relapsers. AIMS: To identify the risk factors for relapse among patients with an end-of-treatment response (ETR). METHODS: We retrospectively analyzed 281 patients consecutively treated with PEG-IFN and ribavirin with a follow-up period of at least 24 weeks. The baseline details collected on each patient included demographic data, histological features, and biochemical profiles. RESULTS: Forty six patients (16.4%) relapsed during the first 6 months of follow-up after discontinuing the therapy. Relapser patients were significantly older, had more steatosis, fibrosis, and showed significantly lower rapid virological response (RVR) rates compared with SVR patients. By logistic regression analysis, only the absence of RVR was found to be significantly associated with relapses in both subgroups of patients with genotypes 1 and 4 (p < 0.004) and those with genotypes 2 and 3 (p < 0.006). Severe fibrosis was also predictive of relapsing disease, but only for genotypes 2 and 3 patients (p < 0.003). During the treatment, serum HCV-RNA decreased more rapidly in patients with SVR compared to non-responder and relapser patients (p < 0.001). Interestingly, relapser patients exhibited an intermediate serum HCV-RNA decay during the first 4 weeks of therapy. CONCLUSION: Among HCV patients treated with PEG-IFN and ribavirin, the absence of RVR was the most important independent predictor of relapse, independent of the HCV genotype. In the subgroup of genotypes 2 and 3 patients, the severity of fibrosis was also an important factor associated with the relapse rate. PMID- 22095533 TI - Prevalence and impact of hepatitis B and C virus co-infections in antiretroviral treatment naive patients with HIV infection at a major treatment center in Ghana. AB - Data on the effects of the presence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients co-infected with these viruses and HIV in West Africa are conflicting and little information is available in Ghana. A cohort of 138 treatment naive individuals infected with HIV was screened for HBV and HCV serologic markers; HBsAg positive patients were tested for HBeAg, anti-HBe, and anti-HBc IgM. The viral load of HIV-1 in the plasma was determined in 81 patients. Eighteen of the 138 patients (13%) and 5 (3.6%) had HBsAg and anti-HCV, respectively. None of the patients had anti-HBc IgM, but 10 (55.6%) and 8 (44.4%) of the 18 patients who were HBsAg positive had HBeAg and anti-HBe, respectively. In patients with measurement of CD4(+) undertaken within 1 month (n = 83), CD4(+) count was significantly lower in patients with HBeAg (median [IQR], 81 [22-144]) as compared to those with anti-HBe (median [IQR], 210 [197-222]) (P = 0.002, CI: 96.46 to 51.21). However, those with HIV mono-infection had similar CD4(+) counts (median [IQR], 57 [14-159]) compared to those with HBeAg (P = 1.0, CI: -71.75 to 73.66). Similar results were obtained if CD4(+) count was measured within 2 months prior to initiation of HAART (n = 119). Generally, HBV and anti-HCV did not affect CD4(+) and viral loads of HIV-1 in plasma but patients with HIV and HBV co-infection who had HBeAg had more severe immune suppression as compared to those with anti-HBe. This may have implication for initiating HAART in HBV endemic areas. PMID- 22095534 TI - Mutations within enhancer II and BCP regions of hepatitis B virus in relation to advanced liver diseases in patients infected with subgenotype B3 in Indonesia. AB - Studies on the characteristics of mutations within the hepatitis B virus (HBV) genome, their roles in the pathogenesis of advanced liver diseases, and the involvement of host properties of HBV-infected individuals have not been conducted in subgenotype B3-infected populations. For addressing this issue, 40 cases with HBV surface antigen (HBsAg)-positive advanced liver diseases, including advanced liver cancer and cirrhosis (male 31, female 9, age 54.4 +/- 11.6-year-old), were collected and compared with 109 cases with chronic hepatitis B (male 71, female 38, age 38.0 +/- 13.4-year-old). Mutations in enhancer II (Enh II) and basal core promoter (BCP)/precore regions were analyzed by PCR-direct sequencing method. HBV viral load was examined by real-time PCR. For all examined regions, the prevalence of mutation was significantly higher in cases with advanced liver diseases. Multivariate analysis showed that, in patients older than 45 years, C1638T and T1753V mutations constituted independent risk factors for the advancement of liver diseases. The presence of C1638T and T1753V mutations may serve as predictive markers for the progression of liver diseases in Indonesia and other countries, where subgenotype B3 infection is prevalent. PMID- 22095535 TI - Human platelet antigen genotype is associated with progression of fibrosis in chronic hepatitis C. AB - Although progression of fibrosis in the chronic hepatitis C depends on environmental, viral, and host factors, genetic polymorphisms have been associated recently with this progression, including the expression of integrins, adhesion proteins. Some integrins expressed on the platelet membrane show polymorphic antigenic determinants called human platelet antigens (HPA), where the major ones are HPA-1, -3, -5. The association between HCV infection and HPA 5b has been demonstrated. Similarly, the HPA profile could determine if HPA is related to progression of fibrosis. The goal of this study was to evaluate the association between the frequencies of HPA-1, -3, and -5 and degree of fibrosis in HCV-infected patients. Genomic DNA from 143 HCV-infected patients was used as the source for HPA genotyping by PCR-SSP or PCR-RFLP. Progression of fibrosis was evaluated using the METAVIR scoring system, and the patients were grouped according to degree of fibrosis into G1 (n = 81, with F1, portal fibrosis without septa or F2, few septa) and G2 (n = 62, with F3, numerous septa, or F4, cirrhosis). Statistical analysis was performed using the proportional odds model. The genotypic frequency of HPA-1a/1b was significantly higher in the patients in G2. To evaluate the influence of the time of infection to the development of fibrosis and its effect on the genetic factor HPA-1, 96 patients from 143 studied were evaluated considering the time of HCV infection, and these results suggest that the HPA-1a/1b genotype promotes the development of fibrosis in HCV infection with time. PMID- 22095536 TI - Predictive value of early viral dynamics during peginterferon and ribavirin combination therapy based on genetic polymorphisms near the IL28B gene in patients infected with HCV genotype 1b. AB - A study was carried out to determine whether early viral dynamics retain prediction of the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy based on different genetic polymorphisms near the IL28B gene, the strongest baseline predictor of response to this therapy. A total of 272 patients infected with hepatitis C virus (HCV) genotype 1b were grouped according to genetic polymorphisms near the IL28B gene (rs8099917). The ability of reduced HCV RNA levels at 4 and 12 weeks after starting therapy to predict a sustained virologic response was evaluated based on these genotypes. Among patients with the TT genotype for rs8099917 (associated with a favorable response), the rates of sustained virologic response were higher in patients with a >=3 log(10) reduction in serum HCV RNA levels at 4 weeks after starting therapy (P < 0.0001). In contrast, among patients with the TG/GG genotype (associated with an unfavorable response), there were no differences in this rate based on the reduction in HCV RNA levels at 4 weeks. Early viral dynamics at 4 weeks after starting therapy retains its predictive value for sustained virologic response in patients with the TT genotype for rs8099917, but not in patients with the TG/GG genotype. Patients who are likely to achieve sustained virologic response despite unfavorable TG/GG genotype cannot be identified based on early viral dynamics during therapy. In contrast, lack of early virologic response at 12 weeks retains a strong predictive value for the failure of sustained virologic response regardless of IL28B polymorphisms, which remains useful as a factor to stop therapy. PMID- 22095537 TI - Prevalence of specific antibody to hepatitis E virus in the general population of the community of Madrid, Spain. AB - Hepatitis E virus (HEV) is an infectious agent causing hepatitis among humans. Although hepatitis E has been reported from many European countries, its incidence in Europe is largely unknown, and the prevalence of the HEV infection is also unknown for most countries of the region. Antibody to HEV (anti-HEV) was tested on 2,305 serum samples from the general population of the Community of Madrid (Spain) collected in the year 2008 among people aged 2-60 years. Total anti-HEV was tested by enzyme-immunoassay (EIA), and reactive samples were retested separately for anti-HEV IgG and IgM by recombinant immunoblot test (RIBT). Fifty samples (2.17%) displayed reactivity for total anti-HEV after EIA testing, and anti-HEV IgG was confirmed by RIBT in 25 (1.08%). The frequency of RIBT-confirmed anti-HEV ranged from 0.97% among the youngest to 3.61% among the oldest, and displayed a statistically significant trend to increasing with age. The rate of RIBT confirmation was also significantly higher among the individuals aged above 20 years old than among those younger of 21 years. HEV infection would be less frequent in the Community of Madrid than in Catalonia or the United Kingdom, and contact with HEV would be very uncommon among children and adolescents of the region. Confirmation of EIA-reactive samples by RIBT reduced the final numbers of anti-HEV testing as much as 50%, and some findings of this study suggest that such testing protocol would reflect better the real prevalence of anti-HEV in settings of low endemicity than the single testing by EIA. PMID- 22095538 TI - Induction of protective immunity in a Syrian hamster model against a cytopathogenic strain of Andes virus. AB - Andes virus (ANDV) is responsible for the Hantavirus Pulmonary Syndrome cases in Argentina and neighboring countries, with moderate to high case-fatality rates. ANDV has some particular features, which make it unique among other members of the Hantavirus genus such as person-to-person transmission and causing a disease similar to Hantavirus Pulmonary Syndrome in the hamster as an animal model. The kinetics of replication in Vero E6 cells of an ANDV strain isolated in Argentina, called Andes/ARG, was studied. Cytopathic effect and the formation of clear plaques were observed and therefore Andes/ARG could be quantified by classic plaque assay. The Andes/ARG strain was found to be highly lethal in Syrian hamsters allowing experiments to demonstrate the protective potential of vaccines. A recombinant nucleocapsid protein of ANDV induced a long lasting antibody response and protective immunity against a homologous challenge, but to a lower extent against heterologous challenge by the Seoul virus. PMID- 22095539 TI - Case report: cytomegalovirus-induced thrombosis in an immunocompetent patient. AB - Thrombotic manifestations of cytomegalovirus infection in immunocompetent individuals are rare. However, it has been postulated that cytomegalovirus infection can be both directly cytopathic and capable of inducing antiphospholipid antibodies due to shared "molecular mimicry" between cytomegalovirus virus antigens and antiphospholipid antibodies. The case of a previously well 30-year-old woman with primary cytomegalovirus infection complicated by splenic infarction and massive pulmonary embolus is described. The patient is unusual given the development of thromboses affecting both the arterial and venous circulation, associated with both transient anticardiolipin antibodies and persistently positive anti-beta(2) glycoprotein I antibodies. The temporal relationship between the primary infection and thrombosis was suggestive of a pathogenic role for cytomegalovirus. PMID- 22095540 TI - Longitudinal analysis of frequency and reactivity of Epstein-Barr virus-specific T lymphocytes and their association with intermittent viral reactivation. AB - Persistent Epstein-Barr virus (EBV) infection is controlled tightly by virus specific T cells. EBV infection is reactivated intermittently over time, even in apparently healthy carriers. Changes in frequency and reactivity of memory T cells, particularly of CD8(+) origin, have not been assessed in this context. It is hypothesized that viral reactivation is facilitated by diminished EBV-specific T-cell immunity. To this end, blood samples from 14 healthy donors were collected at irregular time intervals for a period of about 1 year. Samples were screened for both EBV plasma viremia and increases in viral load in PBMCs as parameters of EBV reactivation. PBMCs were subject to IFN-gamma ELISPOT analysis using the autologous EBV-transformed lymphoblastoid cell line (EBV-LCL) or appropriate HLA class I-restricted EBV peptides as stimulators. Frequencies of epitope-specific CD8(+) T cells were monitored further using HLA tetramers and flow cytometry. Twelve of 14 donors exhibited signs of asymptomatic EBV reactivation. Viral reactivation was accompanied by either substantially decreased IFN-gamma responses against autologous EBV-LCL (eight of 12 study participants) and/or increased responses against particular EBV peptides (six of 12 donors). In seven persons with HLA-A2 and/or -B8 alleles numbers of HLA tetramer-positive CD8(+) T cells also varied over time, but showed no correlation to episodes of detectable viral activity. In summary, IFN-gamma reactivity of EBV-specific T cells is not constant. Viral reactivation is detected preferably at times of diminished EBV LCL-specific cellular immunity. However, increased reactivity of single immunodominant CD8(+) EBV-specific T-cell clones may occur in response to virus replication. PMID- 22095541 TI - Evaluation of mutagenicity and co-mutagenicity of strong static magnetic fields up to 13 Tesla in Escherichia coli deficient in superoxide dismutase. AB - PURPOSE: To evaluate the biological effects of static magnetic fields (SMFs) up to 13 Tesla (T), with respect to superoxide behavior, by determining the effect on mutagenicity in superoxide dismutase (SOD)-deficient Escherichia coli strain QC774, and its parental strain GC4468. MATERIALS AND METHODS: Experimental strains were exposed to a 5, 10, or 13T SMF for 24 h at 37 degrees C in Luria Bertani medium. To evaluate mutagenicity after SMF exposure, the mutation frequency in thymine synthesis genes was determined. The effect of exposure to a 5 or 13T SMF on mutagenicity induced by plumbagin was also investigated. RESULTS: No statistically significant differences in the mutation frequency in thymine synthesis genes were observed between SMF-exposed cells and unexposed cells at any of the applied magnetic flux densities. Furthermore, exposure to SMFs up to 13T did not affect mutagenicity induced by plumbagin. CONCLUSION: Exposure to SMFs up to 13T caused neither mutagenicity nor co-mutagenicity in the SOD deficient E. coli strain QC774 or in its parental strain GC4468, suggesting that exposure to strong SMFs does not affect the behavior of superoxides in these microorganisms. PMID- 22095542 TI - Age determines longitudinal changes in body composition better than menopausal and bone status: the OFELY study. AB - Long-term body composition (BC) changes and their determinants have been rarely explored. We aimed to evaluate BC changes in French women from the Os des Femmes de Lyon (OFELY) cohort and to explore several determinants of those changes. At baseline, premenopausal (PreM) women (n = 145) had lower fat body mass (FM) and greater lean body mass (LM), relative skeletal muscle mass index (RASM), and total body bone mineral content (TBBMC) compared with untreated postmenopausal (PostM) women (n = 412). During a 6-year follow-up, LM and RASM did not change, whereas a significant increase of FM and a decrease of TBBMC were observed in PreM (n = 88) and PeriM women (n = 44; women who became PostM during the follow up). In untreated PostM women, FM increased, whereas LM, RASM, and TBBMC decreased (p < 0.0001). Age was a significant determinant of the changes in BC. After controlling for age, menopausal status was still a significant determinant only for changes in TBBMC. FM, LM, RASM, and TBBMC were higher in women with normal bone mineral density (BMD) compared with women with osteopenia or osteoporosis (p < 0.0001), but after adjusting for age, changes of BC were not significantly different according to the bone status. After controlling for age and menopausal status, levels of P1NP in the highest quartile were associated with a greater decrease of LM and RASM compared with lower levels. In conclusion, BC changes in French women over a 6-year follow-up showed a high interindividual variability. Aging may be the most important determinant of changes in body composition, rather than menopausal and bone status. PMID- 22095543 TI - Bowman-Birk Inhibitor attenuates experimental autoimmune encephalomyelitis by delaying infiltration of inflammatory cells into the CNS. AB - Bowman-Birk Inhibitor (BBI), a serine protease inhibitor derived from soybeans, has anti-inflammatory properties and is able to suppress the development of central nervous system (CNS) autoimmunity in animal models. Experimental autoimmune encephalomyelitis (EAE), a widely used animal model of multiple sclerosis (MS), is characterized by breakdown of the blood-brain barrier and infiltration of inflammatory cells into the CNS, resulting in pathology. In this study, we observed that BBI-treated mice showed delayed onset of EAE and reduced disease severity compared to control mice. BBI-treated mice had fewer inflammatory cells in the CNS including significantly reduced numbers of Th1 and Th17 cells. In the periphery, BBI treatment suppressed the development of encephalitogenic Th1 and Th17 responses early on [day 7 post-immunization (p.i.)], while after disease onset (day 14 p.i.) BBI-treated mice had stronger Th responses, as determined by antigen-specific proliferation and cytokine production. These results demonstrate that BBI treatment temporarily suppressed the development of encephalitogenic responses, but these responses eventually attained normal magnitude. Given that BBI-treated mice exhibited stronger encephalitogenic responses in the periphery during clinically manifesting EAE, delayed disease onset, and reduced numbers of CNS-infiltrating cells, it appears likely that BBI impedes the exit of pathogenic Th1 and Th17 cells from lymphoid organs, thereby delaying their migration into the CNS. PMID- 22095544 TI - Evolution of immunity: no development without risk. AB - Signal transduction by cell surface receptors in the context of heterogeneous and variable cellular environments plays a pivotal role in regulating many biological processes, including development, activation, and homeostasis of the immune system. In some receptors, extracellular ligand-binding and intracellular signaling domains are located on the same protein chain (single-chain receptors), while in the so-called multichain immune recognition receptors (MIRRs), recognition and signaling functions are separated between different protein chains. Why did nature separate recognition and signaling functions for MIRRs, thereby increasing the risk of malfunction and potential attack by pathogens? The risk is real: in order to escape the immune response, viruses are able to disrupt functional coupling between recognition and signaling aspects of MIRR machinery. Intrinsic disorder of intracellular signal-generating regions of MIRRs adds further intrigue to the story. Why did nature select protein disorder for MIRRs to translate recognition of distinct antigens into appropriate activation signals that would induce specific functional outcomes? Here, I suggest that nature takes the risks associated with intrareceptor separation of functions as well as with the chaos and indeterminacy of protein disorder in exchange for providing diversity and variability of signal transduction. Not only does this phenomenon serve as the molecular basis for the development and evolution of the immune and other complex biological systems, but it fits closely to Darwinian evolutionary biology. PMID- 22095545 TI - Fosfomycin/tobramycin for inhalation in patients with cystic fibrosis with pseudomonas airway infection. AB - RATIONALE: Fosfomycin/tobramycin for inhalation (FTI), a unique, broad-spectrum antibiotic combination, may have therapeutic potential for patients with cystic fibrosis (CF). OBJECTIVES: To evaluate safety and efficacy of FTI (160/40 mg or 80/20 mg), administered twice daily for 28 days versus placebo, in patients greater than or equal to 18 years of age, with CF, chronic Pseudomonas aeruginosa (PA) airway infection, and FEV(1) greater than or equal to 25% and less than or equal to 75% predicted. METHODS: This double-blind, placebo-controlled, multicenter study assessed whether FTI/placebo maintained FEV(1) % predicted improvements achieved following a 28-day, open-label, run-in course of aztreonam for inhalation solution (AZLI). MEASUREMENTS AND MAIN RESULTS: A total of 119 patients were randomized to FTI (160/40 mg: n = 41; 80/20 mg: n = 38) or placebo (n = 40). Mean age was 32 years and mean FEV(1) was 49% predicted at screening. Relative improvements in FEV(1) % predicted achieved by the AZLI run-in were maintained in FTI groups compared with placebo (160/40 mg vs. placebo: 6.2% treatment difference favoring FTI, P = 0.002 [primary endpoint]; 80/20 mg vs. placebo: 7.5% treatment difference favoring FTI, P < 0.001). The treatment effect on mean PA sputum density was statistically significant for the FTI 80/20 mg group versus placebo (-1.04 log(10) PA colony-forming units/g sputum difference, favoring FTI; P = 0.01). Adverse events, primarily cough, were consistent with CF disease. Respiratory events, including dyspnea and wheezing, were less common with FTI 80/20 mg than FTI 160/40 mg. No clinically significant differences between groups were reported for laboratory values. CONCLUSIONS: FTI maintained the substantial improvements in FEV(1) % predicted achieved during the AZLI run in and was well tolerated. FTI is a promising antipseudomonal therapy for patients with CF. PMID- 22095546 TI - Regulation of transforming growth factor-beta1-driven lung fibrosis by galectin 3. AB - RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic dysregulated response to alveolar epithelial injury with differentiation of epithelial cells and fibroblasts into matrix-secreting myofibroblasts resulting in lung scaring. The prognosis is poor and there are no effective therapies or reliable biomarkers. Galectin-3 is a beta-galactoside binding lectin that is highly expressed in fibrotic tissue of diverse etiologies. OBJECTIVES: To examine the role of galectin-3 in pulmonary fibrosis. METHODS: We used genetic deletion and pharmacologic inhibition in well-characterized murine models of lung fibrosis. Further mechanistic studies were performed in vitro and on samples from patients with IPF. MEASUREMENTS AND MAIN RESULTS: Transforming growth factor (TGF)-beta and bleomycin-induced lung fibrosis was dramatically reduced in mice deficient in galectin-3, manifest by reduced TGF-beta1-induced EMT and myofibroblast activation and collagen production. Galectin-3 reduced phosphorylation and nuclear translocation of beta-catenin but had no effect on Smad2/3 phosphorylation. A novel inhibitor of galectin-3, TD139, blocked TGF-beta-induced beta-catenin activation in vitro and in vivo and attenuated the late-stage progression of lung fibrosis after bleomycin. There was increased expression of galectin-3 in the bronchoalveolar lavage fluid and serum from patients with stable IPF compared with nonspecific interstitial pneumonitis and controls, which rose sharply during an acute exacerbation suggesting that galectin-3 may be a marker of active fibrosis in IPF and that strategies that block galectin-3 may be effective in treating acute fibrotic exacerbations of IPF. CONCLUSIONS: This study identifies galectin-3 as an important regulator of lung fibrosis and provides a proof of principle for galectin-3 inhibition as a potential novel therapeutic strategy for IPF. PMID- 22095548 TI - The Parker B. Francis Fellowship Program: analysis of 31 years of career development support. AB - RATIONALE: The Parker B. Francis (PBF) Fellowship Program has supported more than 750 M.D., M.D./Ph.D., and Ph.D. fellows since 1976, but there is little information about the effectiveness of the program in fostering successful careers and producing important research. OBJECTIVES: To survey all past PBF Fellows to obtain information about their productivity and career pathways. METHODS: We obtained e-mail addresses for 526 (74%) of the 712 PBF awardees from 1976 to 2006, then sent an e-mail survey to the 526 past fellows and received 365 replies (69% response rate, 49% overall). Survey questions addressed time in research, areas of research, current position and responsibilities, and research funding. MEASUREMENTS AND MAIN RESULTS: Seventy percent of the 365 respondents spend 25% or greater effort in research and 56% report 50% or more effort in research. Respondents have published an average of 2.7 peer-reviewed publications per year, totaling more than 15,678 peer-reviewed publications, of which 1,875 appeared in high-impact journals. Respondents have received more than $1.8 billion in direct research funding since their PBF Fellowships began. Ph.D. awardees spend more time in research than M.D. awardees, and current research effort did not differ by gender. PBF awardees have become prominent leaders in universities, the National Institutes of Health, health care, and industry. CONCLUSIONS: The PBF Program has been highly successful in producing a large number of scientific and clinical leaders in pulmonary and critical care medicine. The results provide comprehensive data about the success of this career development program and provide a model for programs designed to build the workforce in pulmonary and critical care medicine. PMID- 22095547 TI - Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. AB - The National Heart, Lung, and Blood Institute Severe Asthma Research Program (SARP) has characterized over the past 10 years 1,644 patients with asthma, including 583 individuals with severe asthma. SARP collaboration has led to a rapid recruitment of subjects and efficient sharing of samples among participating sites to conduct independent mechanistic investigations of severe asthma. Enrolled SARP subjects underwent detailed clinical, physiologic, genomic, and radiological evaluations. In addition, SARP investigators developed safe procedures for bronchoscopy in participants with asthma, including those with severe disease. SARP studies revealed that severe asthma is a heterogeneous disease with varying molecular, biochemical, and cellular inflammatory features and unique structure-function abnormalities. Priorities for future studies include recruitment of a larger number of subjects with severe asthma, including children, to allow further characterization of anatomic, physiologic, biochemical, and genetic factors related to severe disease in a longitudinal assessment to identify factors that modulate the natural history of severe asthma and provide mechanistic rationale for management strategies. PMID- 22095550 TI - Long-term subjective results of tension-free vaginal tape operation for female urinary stress incontinence. AB - INTRODUCTION AND HYPOTHESIS: The aim of the study was to evaluate the subjective outcome between 1 and 5 years after tension-free vaginal tape (TVT) operation and the need for follow-up. METHODS: A prospective questionnaire study was performed including questions about incontinence, urinary tract infection, emptying problems, the wish for a clinical control and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). RESULTS: One hundred seventy three patients were included. There were more patients with subjective recurrent stress incontinence over the years, but ICIQ-SF was unchanged. There was no rise in patients reporting urge incontinence over the years. Only 11.4% of the patients wished for a clinical control at some time. CONCLUSION: The TVT operation showed a slight degree of subjective deterioration between 1 and 5 years after the operation; however, the ICIQ-SF was unchanged. There seems to be no need for long-term follow-up at the operating department. PMID- 22095549 TI - Metabolic syndrome biomarkers predict lung function impairment: a nested case control study. AB - RATIONALE: Cross-sectional studies demonstrate an association between metabolic syndrome and impaired lung function. OBJECTIVES: To define if metabolic syndrome biomarkers are risk factors for loss of lung function after irritant exposure. METHODS: A nested case-control study of Fire Department of New York personnel with normal pre-September 11th FEV(1) and who presented for subspecialty pulmonary evaluation before March 10, 2008. We correlated metabolic syndrome biomarkers obtained within 6 months of World Trade Center dust exposure with subsequent FEV(1). FEV(1) at subspecialty pulmonary evaluation within 6.5 years defined disease status; cases had FEV(1) less than lower limit of normal, whereas control subjects had FEV(1) greater than or equal to lower limit of normal. MEASUREMENTS AND MAIN RESULTS: Clinical data and serum sampled at the first monitoring examination within 6 months of September 11, 2001, assessed body mass index, heart rate, serum glucose, triglycerides and high-density lipoprotein (HDL), leptin, pancreatic polypeptide, and amylin. Cases and control subjects had significant differences in HDL less than 40 mg/dl with triglycerides greater than or equal to 150 mg/dl, heart rate greater than or equal to 66 bpm, and leptin greater than or equal to 10,300 pg/ml. Each increased the odds of abnormal FEV(1) at pulmonary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the odds by 84%, in a multibiomarker model adjusting for age, race, body mass index, and World Trade Center arrival time. This model had a sensitivity of 41%, a specificity of 86%, and a receiver operating characteristic area under the curve of 0.77. CONCLUSIONS: Abnormal triglycerides and HDL and elevated heart rate and leptin are independent risk factors of greater susceptibility to lung function impairment after September 11, 2001, whereas elevated amylin is protective. Metabolic biomarkers are predictors of lung disease, and may be useful for assessing risk of impaired lung function in response to particulate inhalation. PMID- 22095551 TI - Predicting anal sphincter defects: the value of clinical examination and manometry. AB - INTRODUCTION AND HYPOTHESIS: The aims of this study were, firstly, to determine the diagnostic accuracy of an anal incontinence score, clinical examination and anal manometry in identifying anal sphincter defects and, secondly, to establish manometric cut-off values associated with sphincter defects. METHODS: One hundred fifty-nine women were evaluated by clinical examination, anal manometry and endoanal ultrasound (EAU). Accuracy measures were calculated, using EAU as the gold standard. RESULTS: Perineal body length (p = 0.84) and pelvic floor muscle strength (p = 0.10) were not associated with anal sphincter defects. Anal inspection was associated with anal sphincter defects (p < 0.001), although its sensitivity was low at 26%. The sensitivity of digital rectal examination was 67% and the specificity 55%. Cut-off values of manometric findings were set to maximise sensitivity at 30 mm anal length, 54 mm Hg maximum resting pressure, 95 mm Hg maximum squeeze pressure and 53 mm Hg squeeze increment. CONCLUSIONS: Clinical assessment has a poor sensitivity for detecting anal sphincter defects. The proposed manometric cut-off values can be used to either reassure or identify women who may need further assessment by EAU. PMID- 22095552 TI - TLC bioautographic method for detecting lipase inhibitors. AB - INTRODUCTION: Bioautographic assays using TLC play an important role in the search for active compounds from plants. A TLC bioautographic assay has previously been established for the detection of acetylcholinesterase inhibitors but not for lipases. OBJECTIVE: Development of a TLC bioautographic method for detecting lipase inhibitors in plant extracts. METHODOLOGY: After migration of the plant extracts, the TLC plate was sprayed with alpha-naphtyl acetate and enzyme solutions before incubation at 37 degrees C for 20 min. Finally, the solution of Fast Blue B salt was sprayed onto the TLC plate giving a purple background colouration. RESULTS: Lipase inhibitors were visualised as white spots on the TLC plates. Orlistat (a known lipase inhibitor) inhibited lipase down to 0.01 ug. Methanolic extracts of Camellia sinensis (L.) kuntz and Rosmarinus officinalis L after migration on TLC gave enzymatic inhibition when applied in amounts of 82 and 56 ug, respectively. On the other hand the methanolic extract of Morus alba leaves did not exhibit any lipase inhibitory activity. CONCLUSION: The screening test was able to detect lipase inhibition by pure reference substances and by compounds present in complex matrices, such as plant extracts. PMID- 22095553 TI - RhoC and guanine nucleotide exchange factor Net1 in androgen-unresponsive mouse mammary carcinoma SC-4 cells and human prostate cancer after short-term endocrine therapy. AB - BACKGROUND: Endocrine resistance is a critical issue in managing patients with prostate cancer. This study is undertaken to search for a potential molecular target connected with this process using a model system of androgen-dependent and androgen-unresponsive SC-3 and SC-4 cells. METHODS: Expression profiles, actin stress fiber organization, and the levels of activated Rho GTPases were compared between SC-4 and SC-3 cells using an oligonucleotide microarray, phalloidin staining, and a Rho activation assay. The cell viability was analyzed with a Rho inhibitor or by stable transfection with either a dominant-negative (DN) form of RhoC or a mutant form of NET1 (mutNET1). The expressions of RhoC, NET1, and epithelial-mesenchymal transition (EMT) markers were immunohistochemically analyzed in human prostate cancer specimens after short-term endocrine therapy and in an untreated condition. RESULTS: SC-4 cells exhibited mesenchymal phenotypes with activation of Rho signals. Treatment with a Rho inhibitor suppressed the cell viability in SC-4 cells, but not in SC-3 cells. The cell viability of SC-4 cells stably expressing DN-RhoC and mutNET1 was also attenuated. In the immunohistochemical analysis, NET1 and the EMT marker of N cadherin were expressed at higher levels in prostate cancers after short-term endocrine therapy than in untreated tumors, and RhoC expression was maintained after short-term endocrine therapy. CONCLUSIONS: Rho signaling is involved in the cell survival of SC-4 cells. The higher expressions of RhoC and NET1 in human prostate cancers after short-term endocrine therapy suggest that RhoC and NET1 may become therapeutic targets during endocrine therapy. PMID- 22095554 TI - Development of thermostable Candida antarctica lipase B through novel in silico design of disulfide bridge. AB - Lipase B from Candida antarctica (CalB) is a versatile biocatalyst for various bioconversions. In this study, the thermostability of CalB was improved through the introduction of a new disulfide bridge. Analysis of the B-factors of residue pairs in CalB wild type (CalB-WT) followed by simple flexibility analysis of residues in CalB-WT and its designated mutants using FIRST server were newly proposed to enhance the selective power of two computational tools (MODIP and DbD v1.20) to predict the possible disulfide bonds in proteins for the enhancement of thermostability. Five residue pairs (A162-K308, N169-F304, Q156(-) L163, S50 A273, and S239C-D252C) were chosen and the respective amino acid residues were mutated to cysteine. In the results, CalB A162C-K308C showed greatly improved thermostability while maintaining its catalytic efficiency compared to that of CalB-WT. Remarkably, the temperature at which 50% of its activity remained after 60-min incubation (T6050) of CalB A162C_K308C was increased by 8.5 degrees C compared to that of CalB-WT (55 and 46.5 degrees C, respectively). Additionally, the half-life at 50 degrees C of CalB A162C-K308C was 4.5-fold higher than that of CalB-WT (220 and 49 min, respectively). The improvement of thermostability of CalB A162C-K308C was elucidated at the molecular level by molecular dynamics (MD) simulation. PMID- 22095555 TI - Rosmarinic acid and baicalin epigenetically derepress peroxisomal proliferator activated receptor gamma in hepatic stellate cells for their antifibrotic effect. AB - Hepatic stellate cells (HSCs) undergo myofibroblastic transdifferentiation (activation) to participate in liver fibrosis and identification of molecular targets for this cell fate regulation is essential for development of efficacious therapeutic modalities for the disease. Peroxisomal proliferator-activated receptor gamma (PPARgamma) is required for differentiation of HSCs and its epigenetic repression underlies HSC activation. The herbal prescription Yang-Gan Wan (YGW) prevents liver fibrosis, but its active ingredients and molecular mechanisms are unknown. Here we demonstrate YGW prevents and reverses HSC activation by way of epigenetic derepression of Ppargamma involving reductions in MeCP2 expression and its recruitment to Ppargamma promoter, suppressed expression of PRC2 methyltransferase EZH2, and consequent reduction of H2K27di-methylation at the 3' exon. High-performance liquid chromatography / mass spectrometry (HPLC/MS) and nuclear magnetic resonance (NMR) analyses identify polyphenolic rosmarinic acid (RA) and baicalin (BC) as active phytocompounds. RA and BC suppress the expression and signaling by canonical Wnts, which are implicated in the aforementioned Ppargamma epigenetic repression. RA treatment in mice with existing cholestatic liver fibrosis inhibits HSC activation and progression of liver fibrosis. CONCLUSION: These results demonstrate a therapeutic potential of YGW and its active component RA and BC for liver fibrosis by way of Ppargamma derepression mediated by suppression of canonical Wnt signaling in HSCs. PMID- 22095557 TI - One-dimensional gratings evolving through high-temperature annealing: sine generated solutions. AB - Sine-generated curves (i.e. curves in which the curvature is a sine function of the arc-length parameter) have been used in the past to describe river meanders. Here we show how these curves spontaneously appear during the decay of high aspect-ratio surfaces mediated by surface diffusion. We obtained analytical results for the kinetic evolution of such processes relevant to a wide class of initial geometries. Our theoretical results were satisfactorily compared with numerical simulations and with results from previous approaches to the same problem, and they can be useful for interpreting and designing experiments related to the technologically important process of high-temperature annealing on nano/micro-structured samples. PMID- 22095556 TI - Spectroscopic elucidation of a new heme/copper dioxygen structure type: implications for O...O bond rupture in cytochrome c oxidase. PMID- 22095558 TI - Bilateral neck metastases in upper aero-digestive tract cancer: emphasis on the distribution of lymphatic metastases and prognostic implications. AB - BACKGROUND: Bilateral neck metastases (BNM) in patients with upper aero-digestive tract cancer (UADTC) indicate a poor prognosis. However, the prognostic significance of involved neck node levels has not been determined clearly. In this study, the distribution of neck nodal metastasis and its impact on prognosis were investigated. METHODS: Eighty-two previously untreated UADTC patients with BNM from 2000 to 2007 were included in these analyses. The pathology was mainly squamous cell carcinomas, including nasopharynx undifferentiated carcinoma and excluding salivary and thyroid carcinomas. The distribution and pattern of neck metastases and their prognostic significance were assessed, along with other clinical variables. RESULTS: BNM confined to the upper neck level (I-III) showed a lower rate of distant metastasis compared to BNM beyond I-III levels (13.6% vs. 47.4%, P = 0.001). There was a significant reduction in survival among patients with bilateral lower neck (IV-V) metastases on multivariate analysis (HR: 5.95, 95%CI: 1.51-23.43). However, multi-level involvement itself did not correlate with survival. Subgroup analysis (according to nasopharynx and non-nasopharynx cancer) also confirmed the strong trends of lower neck nodal involvement for poorer survival in both groups. CONCLUSION: BNM at lower neck nodes can be a significant prognostic factor for early systemic dissemination and worse prognosis in UADTC patients. PMID- 22095559 TI - Analysis of the effects of HIV-1 Tat on the survival and differentiation of vessel wall-derived mesenchymal stem cells. AB - HIV infection is an independent risk factor for atherosclerosis development and cardiovascular damage. As vessel wall mesenchymal stem cells (MSCs) are involved in the regulation of vessel structure homeostasis, we investigated the role of Tat, a key factor in HIV replication and pathogenesis, in MSC survival and differentiation. The survival of subconfluent MSCs was impaired when Tat was added at high concentrations (200-1,000 ng/ml), whereas lower Tat concentrations (1-100 ng/ml) did not promote apoptosis. Tat enhanced the differentiation of MSC toward adipogenesis by the transcription and activity upregulation of PPARgamma. This Tat-related modulation of adipogenesis was tackled by treatment with antagonists of Tat-specific receptors such as SU5416 and RGD Fc. In contrast, Tat inhibited the differentiation of MSCs to endothelial cells by downregulating the expression of VEGF-induced endothelial markers such as Flt-1, KDR, and vWF. The treatment of MSCs with Tat-derived peptides corresponding to the cysteine-rich, basic, and RGD domains indicated that these Tat regions are involved in the inhibition of endothelial marker expression. The Tat-related impairment of MSC survival and differentiation might play an important role in vessel damage and formation of the atherosclerotic lesions observed in HIV-infected patients. PMID- 22095560 TI - Selective adsorption of proteins on single-wall carbon nanotubes by using a protective surfactant. AB - The dispersion of highly hydrophobic carbon materials such as carbon nanotubes in biological media is a challenging issue. Indeed, the nonspecific adsorption of proteins occurs readily when the nanotubes are introduced in biological media; therefore, a methodology to control adsorption is in high demand. To address this issue, we developed a bifunctional linker derived from pyrene that selectively enables or prevents the adsorption of proteins on single-wall carbon nanotubes (SWNTs). We demonstrated that it is possible to decrease or completely suppress the adsorption of proteins on the nanotube sidewall by using proper functionalization (either covalent or noncovalent). By subsequently activating the functional groups on the nanotube derivatives, protein adsorption can be recovered and, therefore, controlled. Our approach is simple, straightforward, and potentially suitable for other biomolecules that contain thio or amino groups available for coupling. PMID- 22095561 TI - Myriophyllum aquaticum versus Lemna minor: sensitivity and recovery potential after exposure to atrazine. AB - The relative sensitivity and recovery potential of two aquatic macrophyte species, Lemna minor and Myriophyllum aquaticum, exposed to atrazine (concentration ranges 80-1,280 ug/L and 40-640 ug/L, respectively) were evaluated using slightly adapted standard protocol for Lemna spp.: relative growth rates (RGR) and yield of both plants were measured in 3-d-long intervals during the exposure and recovery phase. Myriophyllum aquaticum was also exposed to atrazine spiked sediment (0.1-3.7 ug/g) in a water-free system. The results of M. aquaticum sediment contact tests showed that root- and shoot-based growth parameters are equally sensitive endpoints. In the water (sediment-free) test system, L. minor recovered after short (3 d) and longer exposure (7 d) to all atrazine concentrations after only a 5- to 6-d-long recovery phase. The recovery of M. aquaticum after short exposure was slower and less efficient: after 12 d of recovery phase the final biomass of plants exposed to 380 and 640 ug/L was below the initial values. The last interval RGR provides a good indication of plant recovery potential regardless of species growth strategy. If compared to L. minor, the difference in growth rate, sensitivity, lag phase, recovery potential from water-column substances, and also suitability for studies investigating the effect of sediment-bound pollutants advocates the use of M. aquaticum as an additional macrophyte species in risk assessment. PMID- 22095562 TI - LiNi(0.5)Mn(1.5)O4 hollow structures as high-performance cathodes for lithium-ion batteries. PMID- 22095563 TI - Super folds, networks, and barriers. AB - Exhaustive enumeration of sequences and folds is conducted for a simple lattice model of conformations, sequences, and energies. Examination of all foldable sequences and their nearest connected neighbors (sequences that differ by no more than a point mutation) illustrates the following: (i) There exist unusually large number of sequences that fold into a few structures (super-folds). The same observation was made experimentally and computationally using stochastic sampling and exhaustive enumeration of related models. (ii) There exist only a few large networks of connected sequences that are not restricted to one fold. These networks cover a significant fraction of fold spaces (super-networks). (iii) There exist barriers in sequence space that prevent foldable sequences of the same structure to "connect" through a series of single point mutations (super barrier), even in the presence of the sequence connection between folds. While there is ample experimental evidence for the existence of super-folds, evidence for a super-network is just starting to emerge. The prediction of a sequence barrier is an intriguing characteristic of sequence space, suggesting that the overall sequence space may be disconnected. The implications and limitations of these observations for evolution of protein structures are discussed. PMID- 22095564 TI - Pathogenic orphan transduction created by a nonreference LINE-1 retrotransposon. AB - Long INterspersed Element-1 (LINE-1) retrotransposons comprise 17% of the human genome, and move by a potentially mutagenic "copy and paste" mechanism via an RNA intermediate. Recently, the retrotransposition-mediated insertion of a new transcript was described as a novel cause of genetic disease, Duchenne muscular dystrophy, in a Japanese male. The inserted sequence was presumed to derive from a single-copy, noncoding RNA transcribed from chromosome 11q22.3 that retrotransposed into the dystrophin gene. Here, we demonstrate that a nonreference full-length LINE-1 is situated in the proband and maternal genome at chromosome 11q22.3, directly upstream of the sequence, whose copy was inserted into the dystrophin gene. This LINE-1 is highly active in a cell culture assay. LINE-1 insertions are often associated with 3' transduction of adjacent genomic sequences. Thus, the likely explanation for the mutagenic insertion is a LINE-1 mediated 3' transduction with severe 5' truncation. This is the first example of LINE-1-induced human disease caused by an "orphan" 3' transduction. PMID- 22095565 TI - Person-to-person transmission of severe fever with thrombocytopenia syndrome bunyavirus through blood contact. AB - Severe fever with thrombocytopenia syndrome bunyavirus is a newly discovered bunyavirus with high pathogenicity to human. The transmission model has been largely uncharacterized. Investigation on a cluster of severe fever with thrombocytopenia syndrome cases provided evidence of person-to-person transmission through blood contact to the index patient with high serum virus load. PMID- 22095566 TI - Bronchiectasis is associated with human T-lymphotropic virus 1 infection in an Indigenous Australian population. AB - BACKGROUND: Recent studies suggest that infection with human T-lymphotropic virus 1 (HTLV-1) might be associated with bronchiectasis among Indigenous Australians. The present study compared the clinical characteristics and outcomes of bronchiectasis in this population, according to HTLV-1 serologic status. METHODS: We performed a retrospective cohort study of Indigenous adults with bronchiectasis and known HTLV-1 serologic status admitted to Alice Springs Hospital, central Australia, from January 2000 through December 2006. RESULTS: Among 89 Indigenous adults whose HTLV-1 serologic status was confirmed, 52 (58.4%) were HTLV-1 seropositive. Differences between HTLV-1-seropositive and HTLV-1-seronegative groups were apparent in childhood presentations and adult outcomes. Among adults, an increasing number of bronchiectatic lobes (univariable odds ratio [OR], 1.51; 95% confidence interval [CI]; 1.03-2.20; P = .033) and the presence of ground-glass opacities at chest high-resolution computed tomography (univariable OR, 8.54; 95% CI, 1.04-70.03; P = .046) predicted HTLV-1 infection. Cor pumonale (HTLV-1-positive group, 10/52; HTLV-1-negative group, 1/37; P = .023) was more frequent among HTLV-1-seropositive adults, who also experienced a higher disease-specific mortality (univariable OR, 5.78; 95% CI, 1.17-26.75; P = .028). Only HTLV-1-seropositive patients were admitted specifically for the treatment of infected skin lesions, and this finding predicted death (multivariable OR, 6.77; 95% CI, 1.46-31.34; P = .014). Overall mortality was high; 34.2% of the cohort died at a median age of 42.5 years. CONCLUSIONS: HTLV-1 infection contributes to the risk of developing bronchiectasis and worsens outcomes among Indigenous Australians. PMID- 22095567 TI - Magnitude of potential biases in a simulated case-control study of the effectiveness of influenza vaccination. AB - BACKGROUND: Many influenza vaccine effectiveness estimates have been made using case-control methods. Although several forms of bias may distort estimates of vaccine effectiveness derived from case-control studies, there have been few attempts to quantify the magnitude of these biases. METHODS: We estimated the magnitude of potential biases in influenza vaccine effectiveness values derived from case-control studies from several factors, including bias from differential use of diagnostic testing based on influenza vaccine status, imperfect diagnostic test characteristics, and confounding. A decision tree model was used to simulate an influenza vaccine effectiveness case-control study in children. Using probability distributions, we varied the value of factors that influence vaccine effectiveness estimates, including diagnostic test characteristics, vaccine coverage, likelihood of receiving a diagnostic test for influenza, likelihood that a child hospitalized with acute respiratory infection had influenza, and others. Bias was measured as the difference between the effectiveness observed in the simulated case-control study and a true underlying effectiveness value. RESULTS AND CONCLUSIONS: We found an average difference between observed and true vaccine effectiveness of -11.9%. Observed vaccine effectiveness underestimated the true effectiveness in 88% of model iterations. Diagnostic test specificity exhibited the strongest association with observed vaccine effectiveness, followed by the likelihood of receiving a diagnostic test based on vaccination status and the likelihood that a child hospitalized with acute respiratory infection had influenza. Our findings suggest that the potential biases in case-control studies that we examined tend to result in underestimates of true influenza vaccine effects. PMID- 22095568 TI - Paradoxical immune reconstitution inflammatory syndrome in HIV-infected patients treated with combination antiretroviral therapy after AIDS-defining opportunistic infection. AB - BACKGROUND: The incidence of immune reconstitution inflammatory syndrome (IRIS) when antiretroviral therapy (ART) is initiated after an AIDS-defining opportunistic infection (OI) is uncertain and understudied for the most common OIs. METHODS: We examined patients in the University of Washington Human Immunodeficiency Virus Cohort initiating potent ART subsequent to an AIDS defining OI. IRIS was determined through retrospective medical record review and adjudication using a standardized data collection process and clinical case definition. We compared demographic and clinical characteristics, and immunologic changes in patients with and without IRIS. RESULTS: Among 196 patients with 260 OIs, 21 (11%; 95% confidence interval, 7%-16%) developed paradoxical IRIS in the first year on ART. The 3 most common OIs among study patients were Pneumocystis pneumonia (PCP, 28%), Candida esophagitis (23%), and Kaposi sarcoma (KS, 16%). Cumulative 1-year incidence of IRIS was 29% (12/41) for KS, 16% (4/25) for tuberculosis, 14% (1/7) for Cryptococcus, 10% (1/10) for Mycobacterium avium complex, and 4% (3/72) for PCP. Morbidity and mortality were highest in those with visceral KS-IRIS compared with other types of IRIS (100% [6/6] vs 7% [1/15], P < .01). Patients with mucocutaneous KS and tuberculosis-IRIS experienced greater median increase in CD4(+) cell count during the first 6 months of ART compared with those without IRIS (+158 vs +53 cells/MUL, P = .04, mucocutaneous KS; +261 vs +113, P = .04, tuberculosis). CONCLUSIONS: Cumulative incidence and features of IRIS varied depending on the OI. IRIS occurred in >10% of patients with KS, tuberculosis, or Cryptococcus. Visceral KS-IRIS led to considerable morbidity and mortality. PMID- 22095569 TI - Ribosomal RNA evidence of ocular Chlamydia trachomatis infection following 3 annual mass azithromycin distributions in communities with highly prevalent trachoma. AB - Twelve trachoma-hyperendemic communities were treated with 3 annual mass azithromycin distributions. Children aged 0-9 years were monitored 1 year following the third treatment. An RNA-based test detected ocular chlamydial infection in more children than did a DNA-based test (6.9% vs 4.2%), and in a larger number of communities (8 vs 7). PMID- 22095570 TI - Adverse outcome analyses of observational data: assessing cardiovascular risk in HIV disease. AB - Clinical decisions are ideally based on randomized trials but must often rely on observational data analyses, which are less straightforward and more influenced by methodology. The authors, from a series of expert roundtables convened by the Forum for Collaborative HIV Research on the use of observational studies to assess cardiovascular disease risk in human immunodeficiency virus infection, recommend that clinicians who review or interpret epidemiological publications consider 7 key statistical issues: (1) clear explanation of confounding and adjustment; (2) handling and impact of missing data; (3) consistency and clinical relevance of outcome measurements and covariate risk factors; (4) multivariate modeling techniques including time-dependent variables; (5) how multiple testing is addressed; (6) distinction between statistical and clinical significance; and (7) need for confirmation from independent databases. Recommendations to permit better understanding of potential methodological limitations include both responsible public access to de-identified source data, where permitted, and exploration of novel statistical methods. PMID- 22095571 TI - Performance of health literacy tests among older adults with diabetes. AB - BACKGROUND: Knowing a patient's health literacy can help clinicians and researchers anticipate a patient's ability to understand complex health regimens and deliver better patient-centered instructions and information. Poor health literacy has been linked with lower ability to function adequately in health care systems. OBJECTIVE: We evaluated and compared three measures of health literacy and performance among older patients with diabetes. DESIGN: Cross-sectional study utilizing in-person interviews conducted in participants' homes. PARTICIPANTS: A tri-ethnic sample (n = 563) of African American, American Indian, and white older adults with diabetes from eight counties in south-central North Carolina. MAIN MEASURE: Participants completed interviews and health literacy assessments using the Short-Form Test of Functional Health Literacy in Adults (S-TOFHLA), the Rapid Estimates of Adult Literacy in Medicine Short-Form (REALM-SF), or the Newest Vital Signs (NVS). Scores for reading comprehension and numeracy were calculated. RESULTS: Over 90% completed the S-TOFHLA numeracy and approximately 85% completed the S-TOFHLA reading and REALM-SF. Only 73% completed the NVS. The correlation of S-TOFHLA total scores with REALM-SF and NVS were 0.48 and 0.54, respectively. Age, gender, ethnic, educational and income differences in health literacy emerged for several instruments, but the pattern of results across the instruments was highly variable. CONCLUSIONS: A large segment of older adults is unable to complete short-form assessments of health literacy. Among those who were able to complete assessments, the REALM-SF and NVS performed comparably, but their relatively low convergence with the S-TOFHLA raises questions about instrument selection when studying health literacy of older adults. PMID- 22095572 TI - Impact of comorbidity on mortality among older persons with advanced heart failure. AB - BACKGROUND: Care for patients with advanced heart failure (HF) has traditionally focused on managing HF alone; however, little is known about the prevalence and contribution of comorbidity to mortality among this population. We compared the impact of comorbidity on mortality in older adults with HF with high mortality risk and those with lower mortality risk, as defined by presence or absence of a prior hospitalization for HF, respectively. METHODS: This was a retrospective cohort study (2002-2006) of 18,322 age-matched and gender-matched Medicare beneficiaries. We used the baseline year of 2002 to ascertain HF hospitalization history, in order to identify beneficiaries at either high or low risk of future HF mortality. We calculated the prevalence of 19 comorbidities and overall comorbidity burden, defined as a count of conditions, among both high and low risk beneficiaries, in 2002. Proportional hazards regressions were used to determine the effect of individual comorbidity and comorbidity burden on mortality between 2002 and 2006 among both groups. RESULTS: Most comorbidities were significantly more prevalent among hospitalized versus non-hospitalized beneficiaries; myocardial infarction, atrial fibrillation, kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and hip fracture were more than twice as prevalent in the hospitalized group. Among hospitalized beneficiaries, myocardial infarction, diabetes, COPD, CKD, dementia, depression, hip fracture, stroke, colorectal cancer and lung cancer were each significantly associated with increased hazard of dying (hazard ratios [HRs]: 1.16-1.93), adjusting for age, gender and race. The mortality risk associated with most comorbidities was higher among non-hospitalized beneficiaries (HRs: 1.32-3.78). CONCLUSIONS: Comorbidity confers a significantly increased mortality risk even among older adults with an overall high mortality risk due to HF. Clinicians who routinely care for this population should consider the impact of comorbidity on outcomes in their overall management of HF. Such information may also be useful when considering the risks and benefits of aggressive, high-intensity life-prolonging interventions. PMID- 22095574 TI - Overexpression of factor inhibiting HIF-1 enhances vessel maturation and tumor growth via platelet-derived growth factor-C. AB - Recent studies have revealed that the maturation state of vessels in tumors, in addition to vascularity, is a critical determinant of tumor growth. The role of oxygen-dependent signaling pathways in hypoxia-stimulated angiogenesis is well established, however, little is known about their impact on vessel maturation in tumors. Here, we have studied the function of the cellular oxygen sensor, factor inhibiting HIF-1 (FIH), which controls the activity of hypoxia-inducible factor 1. FIH silencing in mouse LM8 osteosarcoma stimulated angiogenesis but did not influence tumor growth. In contrast, FIH overexpression led to increased pericyte coverage of the tumor vasculature, reduced vessel leakiness and enhanced tumor growth. Vessel maturation was paralleled by up-regulation of platelet-derived growth factor (PDGF)-C in tumors and expression of PDGF receptor-alpha on pericytes. Ablation of PDGF-C in FIH-overexpressing tumor cells reduced pericyte coverage and tumor growth. Our data suggest that FIH-mediated PDGF-C induction in LM8 osteosarcoma stimulates the recruitment of PDGFR-alpha positive pericytes to the tumor vasculature, leading to vessel maturation and enhanced tumor growth. PMID- 22095573 TI - Factors associated with pneumonia outcomes: a nationwide population-based study over the 1997-2008 period. AB - BACKGROUND: Pneumonia is the most common infectious cause of death worldwide. Over the last decade, patient characteristics and health care factors have changed. However, little information is available regarding systematically and simultaneously exploring effects of these changes on pneumonia outcomes. OBJECTIVES: We used nationwide longitudinal population-based data to examine which patient characteristics and health care factors were associated with changes in 30-day mortality rates for pneumonia patients. DESIGN: Trend analysis using multilevel techniques. SETTING: General acute care hospitals throughout Taiwan. PARTICIPANTS: A total of 788,011 pneumonia admissions. MEASUREMENTS: Thirty-day mortality rates. Taiwan's National Health Insurance claims data from 1997 to 2008 were used to identify the effects of patient characteristics and health care factors on 30-day mortality rates. RESULTS: Male, older, or severely ill patients, patients with more comorbidities, weekend admissions, larger reimbursement cuts and lower physician volume were associated with increased 30 day mortality rates. Moreover, there were interactions between patient age and trend on mortality. CONCLUSIONS: Male, older or severely ill patients with pneumonia have higher 30-day mortality rates. However, mortality gaps between elderly and young patients narrowed over time; namely, the decline rate of mortality among elderly patients was faster than that among young patients. Pneumonia patients admitted on weekends also have higher mortality rates than those admitted on weekdays. The mortality of pneumonia patients rises under increased financial strain from cuts in reimbursement such as the Balanced Budget Act in the United States or global budgeting. Higher physician volume is associated with lower mortality rates. PMID- 22095575 TI - Targeting treatment-resistant depression. AB - Only 50% of depressed patients achieve remission of symptoms after 2 trials of antidepressants. Therefore one half of patients are considered treatment resistant. Studies have shown that with each failed antidepressant, chances of remission continue to decline. Untreated depressive symptoms lead to impaired social and occupational function, decline of physical health, suicidal thoughts, and increased health care utilization. Clinicians recognize there is an urgent need to find an efficacious treatment, but it becomes more difficult to decide on an appropriate therapy once a patient has failed 2 to 3 trials of antidepressants. An evidence-based review was performed to assess the efficacy and safety of several different antidepressant strategies to help the clinician decide which may be beneficial for specific patients. PMID- 22095576 TI - Atypical antipsychotic drugs in the treatment of Parkinson's disease. AB - Parkinson's disease (PD) patients often develop psychotic symptoms that severely affect quality of life and limit the use of medications to ameliorate motor symptoms. Psychotic symptoms are a major cause for nursing home placement. While these symptoms do not always require treatment, they often do but antipsychotic drugs all share the common pharmacological mechanism of blocking dopamine D2 receptors which may worsen motor problems in this very vulnerable population. Double blind, placebo controlled trials (DBPCT) have shown that clozapine is effective at controlling the psychotic symptoms at doses far below those used in schizophrenia, without worsening motor function, even improving tremor. DBPCT have demonstrated that olanzapine worsens motor function without improving psychosis. Quetiapine has been shown in DBPCT to be free of motor side effects in PD patients but not effective, whereas many open label studies have indicated that quetiapine is effective. The other atypical have been the subjects of conflicting open label reports. The effects of the atypicals in PD psychosis is reviewed. PMID- 22095578 TI - Pharmacist-managed antimicrobial stewardship program for patients discharged from the emergency department. AB - Positive outcomes of antimicrobial stewardship programs in the inpatient setting are well documented, but the benefits for patients not admitted to the hospital remain less clear. This report describes a retrospective case-control study of patients discharged from the emergency department (ED) with subsequent positive cultures conducted to determine whether integrating antimicrobial stewardship responsibilities into practice of the emergency medicine clinical pharmacist (EPh) decreased times to positive culture follow-up, patient or primary care provider (PCP) notification, and appropriateness of antimicrobial therapy. Pre- and post-implementation groups of an EPh-managed antimicrobial stewardship program were compared. Positive cultures were identified in 177 patients, 104 and 73 in pre- and post-implementation groups, respectively. Median time to culture review in the pre-implementation group was 3 days (range 1-15) and 2 days (range 0-4) in the post-implementation group (P = .0001). There were 74 (71.2%) and 36 (49.3%) positive cultures that required notification in the pre- and post implementation groups, respectively, and the median time to patient or PCP notification was 3 days (range 1-9) and 2 days (range 0-4) in the 2 groups (P = .01). No difference was seen in the appropriateness of therapy. In conclusion, EPh involvement reduced time to positive culture review and time to patient or PCP notification when indicated. PMID- 22095577 TI - Misuse of prescribed stimulant medication for ADHD and associated patterns of substance use: preliminary analysis among college students. AB - OBJECTIVES: To explore the prevalence and characteristics associated with college students who misuse their prescribed stimulants for attention-deficit hyperactivity disorder (ADHD) and examine diversion and substance use behaviors as a function of misuse. METHODS: Cohort of 55 past-year prescribed stimulant users was identified from a random sample (n = 1738) at a large Midwestern research university following the self-administration of a web-based survey. An index was created to assess misuse of prescribed stimulants (i.e., Misuse Index). RESULTS: Of 55 college students who reported past-year use of prescribed stimulants for ADHD, 22 (40%) endorsed at least one item on the misuse index. The most frequently endorsed misuse items were used too much (36%), self-reported misuse (19%), and intentionally used with alcohol or other drugs (19%). Misusers of prescribed stimulant medication were more likely to report cigarette smoking (p = 0.022), binge drinking (p = 0.022), illicit use of cocaine (p = 0.032), and screen positive on the Drug Abuse Screening test (DAST-10) criteria (p = 0.002). The bivariate odds ratio for the DAST-10 findings was 8.4 (95% CI: 2.0-34.6). Diversion of prescribed stimulants was common (36%) and occurred more frequently among stimulant misusers (57%; p = 0.008). CONCLUSION: There is a strong relationship between misuse of prescribed stimulants for ADHD and substance use behaviors, as well as other deleterious behaviors such as diversion. These findings suggest the need for close screening, assessment, and therapeutic monitoring of medication use in the college population. PMID- 22095579 TI - Treatments for methamphetamine abuse: a literature review for the clinician. AB - Methamphetamine (METH) use and dependence is a serious public health concern with implications across multiple areas from societal impact to burden on psychiatric and medical resources. An estimated 8% of admissions to substance abuse treatment programs are related to stimulants with METH/amphetamine abuse. To date, effective pharmacotherapy options to enhance abstinence have not been identified. The objective of this article is to critically review the literature of METH treatment options. Preclinical research and human research with compounds not yet available commercially in the United States will not be included. A literature review was conducted for research on pharmacological treatments for METH use and addiction. Trial information on the use of sertraline, bupropion, mirtazapine, modafinil, dextroamphetamine, ondansetron, risperidone, aripiprazole, baclofen, and gabapentin was reviewed. Aripiprazole trials appeared in the reviewed literature more frequently than the other medications. Based on the findings of this review, no single medication demonstrated consistent efficacy and each trial contained a variety of methodological limitations. PMID- 22095580 TI - Valproic acid in dementia: does an optimal dose exist? AB - Valproic acid is widely used in the treatment of behavioral disturbances in patients with dementia; however, there is uncertainty about its dosing and studies have reported mixed findings. The current article examines published trials of valproic acid in the treatment of patients with dementia to identify whether an optimal dosing strategy exists. Secondarily, valproic acid dosing from published studies is compared with a real-world 5-year sample of valproic acid prescribing. Twenty studies met selection criteria and were included in the review. Based primarily on uncontrolled trials and the current retrospective study, valproic acid serum levels between 40 and 60 mcg/mL and relatively low doses (ie, 7-12 mg/kg per d) are associated with improvements in agitation in some patients with dementia. At the same time, similar valproic acid levels produced no significant behavioral improvements in most placebo-controlled studies and led to substantial side effects in some patients. Considerable trial design differences exist between controlled and uncontrolled trials. Overall, valproic acid appears to have limited efficacy as monotherapy in many patients with dementia. Its optimal role may be in combination with other psychotropics as a treatment of agitation associated with dementia. PMID- 22095581 TI - Low bone mass and high material bone density in two patients with Loeys-Dietz syndrome caused by transforming growth factor beta receptor 2 mutations. AB - Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by heterozygous mutations in the genes encoding transforming growth factor beta receptor 1 or 2 (TGFBR1 or TGFBR2). Although an association between LDS and osteoporosis has been reported, the skeletal phenotype regarding bone mass is not well characterized. Here, we report on two LDS patients with mutations in TGFBR2. Patient 1 was a 24-year-old man who had a total of three fractures involving the left radius, the left metacarpal, and the right femur. At the age of 14 years, lumbar spine areal bone mineral density Z-score was -4.0 and iliac bone histomorphometry showed elevated bone turnover (bone formation rate per bone surface: 91 um3/um2/year; age-matched control values 37 [10], mean [SD]) and mildly low trabecular bone volume per tissue volume (17.2%; age-matched control values 25.7 [5.3]). Bone mineralization density distribution (BMDD) in trabecular bone was increased (Ca(Peak) 22.70 wt% Ca; age-matched control values 21.66 [0.52]). Patient 2, a 17-year-old girl, suffered from diffuse bone pain but had not sustained fractures. At 14 years of age, her lumbar spine areal bone mineral density Z-score was -3.4. Iliac bone histomorphometry at that age confirmed low bone mass (bone volume to tissue volume 10.1%, same control values as above) and high bone turnover (bone formation rate per bone surface 70 um3/um2/year). BMDD in trabecular bone was significantly shifted toward increased mineralization (Ca(Peak) 22.36 wt% Ca). Thus, it appears that LDS can be associated with low bone mass and high bone turnover but increased matrix mineralization of trabecular bone. PMID- 22095582 TI - Heuristic linear mapping of physiological parameters in dynamic contrast-enhanced MRI without T1 measurement and contrast agent concentration. AB - PURPOSE: To present a novel heuristic linear mapping method to individually estimate physiological parameters for Tofts model without T(1) measurement and contrast agent concentration. MATERIALS AND METHODS: A linear relationship was used for k(ep) mapping through a heuristic time intensity curve (TIC) shape factor (TSF). K(trans) maps were subsequently estimated using k(ep) maps and another approximate linear model derived from the Tofts model. Twenty-seven patients with head-and-neck squamous cell carcinoma received dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Physiological parameters maps were obtained using this heuristic linear mapping method and compared to the maps obtained by the normal nonlinear least-square fitting with T(1) measurement. RESULTS: High linearity (R(2) >0.95) between k(ep) and TSF was found in all patients for k(ep) <5/min. This linearity is robust for TSF timepoint selection. The k(ep) maps generated by this linear fitting were highly consistent with those by the normal nonlinear approach (P > 0.05). The K(trans) maps were consistent with the normally derived maps in pattern distribution but the absolute value might be scaled due to the assumption of the reference K(trans) value. CONCLUSION: This novel method generates reliable and consistent physiological parameter maps with significantly lower computation complexity than the multiparameter nonlinear fitting. The DCE-MRI scan time can be greatly shortened without T(1) mapping. PMID- 22095583 TI - A general and expedient synthesis of 5- and 6-membered cyclic carbonates by palladium-catalyzed oxidative carbonylation of 1,2- and 1,3-diols. AB - We present a general, practical, and efficient approach to 5- and 6-membered organic carbonates by palladium-catalyzed direct oxidative carbonylation of 1,2- and 1,3-diols, respectively. Reactions were carried out at 100 degrees C in N,N dimethylacetamide as the solvent under 20 atm (at 25 degrees C; 1 atm=101.3 kPa) of a 4:1 v/v CO/air mixture in the presence of 0.5-2 mol % of PdI(2) and KI (KI/PdI(2) molar ratio=10). Excess dehydrating agent, such as trimethyl orthoacetate, was necessary in several cases to obtain appreciable results. The method could also be applied to the synthesis of a high-value-added glycerol carbonate from glycerol, a readily available raw material. When applied to alpha D-glucose, a double carbonylation process took place, with direct formation of alpha-D-glucofuranose 1,2:5,6-dicarbonate. PMID- 22095584 TI - Silica-modified oligonucleotide-gold nanoparticle conjugate enables closed-tube colorimetric polymerase chain reaction. AB - A facile silica coating significantly enhances the thermal stability and polymerase chain reaction (PCR) compatibility of oligonucleotide-gold nanoparticle conjugates, thus enabling colorimetric detection of PCR results in a closed-tube format. This method is specific, sensitive, and generally applicable. Its simplicity, visual readout, and carryover contamination-free features hold promise for point-of-care or on-site DNA testing. PMID- 22095585 TI - Simultaneous determination of four sesquiterpenoids in Atractylodes Macrocephala Rhizoma by GC-FID: optimisation of an ultrasound-assisted extraction by central composite design. AB - INTRODUCTION: Atractylodes Macrocephala Rhizoma (AMR) is a traditional Chinese medicine containing several sesquiterpenoids with a series of effects. These bioactive compounds may be used as chemical markers for the quality control of AMR. It is necessary to optimise the extraction method and conditions in order to improve extraction productivity. OBJECTIVE: To develop a simple and effective method for the extraction of sesquiterpenoids from AMR and then to simultaneously determine four sesquiterpenoids, selina-4 (14), 7(11)-dien-8-one (SA), atractylenolide II (AII), atractylenolide III (AIII) and atractylenolide VII (AVII), in AMR. METHODOLOGY: Ultrasound-assisted extraction (UAE) was optimised by central composite design (CCD) to obtain the maximum efficiency. The gas chromatography method was validated and applied for the quantification of four sesquiterpenoids. RESULTS: The optimum values of factors were: particle size (120 mesh), extraction time (26 min), extraction temperature (39 degrees C) and 31 mL of chloroform. The selectivity, linear range, limits of detection (LOD) and quantification (LOQ), accuracy, precision and repeatability of the method developed indicated its validity. The application of the method showed that the contents of four sesquiterpenoids in AMR were rather variable. CONCLUSION: The results indicated that the described GC method could be used for the quality control of AMR and its related preparations. Meanwhile, this research revealed that UAE under optimum conditions could be considered as a powerful tool for the extraction of phytochemicals from plants. PMID- 22095586 TI - Cross-talk between endothelial and breast cancer cells regulates reciprocal expression of angiogenic factors in vitro. AB - Reciprocal growth factor exchange between endothelial and malignant cells within the tumor microenvironment may directly stimulate neovascularization; however, the role of host vasculature in regulating tumor cell activity is not well understood. While previous studies have examined the angiogenic response of endothelial cells to tumor-secreted factors, few have explored tumor response to endothelial cells. Using an in vitro co-culture system, we investigated the influence of endothelial cells on the angiogenic phenotype of breast cancer cells. Specifically, VEGF, ANG1, and ANG2 gene and protein expression were assessed. When co-cultured with microvascular endothelial cells (HMEC-1), breast cancer cells (MDA-MB-231) significantly increased expression of ANG2 mRNA (20 fold relative to MDA-MB-231 monoculture). Moreover, MDA-MB-231/HMEC-1 co-cultures produced significantly increased levels of ANG2 (up to 580 pg/ml) and VEGF protein (up to 38,400 pg/ml) while ANG1 protein expression was decreased relative to MDA-MB-231 monocultures. Thus, the ratio of ANG1:ANG2 protein, a critical indicator of neovascularization, shifted in favor of ANG2, a phenomenon known to correlate with vessel destabilization and sprouting in vivo. This angiogenic response was not observed in nonmalignant breast epithelial cells (MCF-10A), where absolute protein levels of MCF-10A/HMEC-1 co-cultures were an order of magnitude less than that of the MDA-MB-231/HMEC-1 co-cultures. Results were further verified with a functional angiogenesis assay demonstrating well-defined microvascular endothelial cell (TIME) tube formation when cultured in media collected from MDA-MB-231/HMEC-1 co-cultures. This study demonstrates that the angiogenic activity of malignant mammary epithelial cells is significantly enhanced by the presence of endothelial cells. PMID- 22095587 TI - Photoemission and LEED study of the Sn/Rh(111) surface--early oxidation steps and thermal stability. AB - We have deposited two monolayers of Sn onto Rh(111) single crystal. After the deposition, no ordered structure was revealed by low energy electron diffraction (LEED). We oxidized the obtained system in a low-pressure oxygen atmosphere at 420 K. The oxidized sample was then gradually heated to study the thermal stability of the oxide layer. We characterized the system by synchrotron radiation stimulated photoelectron spectroscopy and LEED. Valence band and core level photoelectron spectra of rhodium, tin and oxygen were used to study the oxidation of the Sn-Rh(111) surface and its behaviour upon annealing. A low stoichiometric oxide of Sn was created on the surface. The oxidation process did not continue towards creation of SnO(2) with higher oxygen dose. The annealing at 970 K caused decomposition of the surface oxide of Sn and creation of an ordered (?3 * ?3)R30 degrees Sn-Rh(111) surface alloy. PMID- 22095589 TI - [16]Cloverphene: a clover-shaped cata-condensed nanographene with sixteen fused benzene rings. PMID- 22095588 TI - Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease. AB - The polymorphism, KLF6-IVS1-27A, in the Kruppel-like factor 6 (KLF6) transcription factor gene enhances its splicing into antagonistic isoforms and is associated with delayed histological progression of nonalcoholic fatty liver disease (NAFLD). To explore a potential role for KLF6 in the development of insulin resistance, central to NAFLD pathogenesis, we genotyped KLF6-IVS1-27 in healthy subjects and assayed fasting plasma glucose (FPG) and insulin sensitivities. Furthermore, we quantified messenger RNA (mRNA) expression of KLF6 and glucokinase (GCK), as an important mediator of insulin sensitivity, in human livers and in liver tissues derived from a murine Klf6 knockdown model (DeltaKlf6). Klf6 overexpression studies in a mouse hepatocyte line were utilized to mechanistically link KLF6 with Gck promoter activity. KLF6-IVS1-27Gwt (i.e., less KLF6 splicing) was associated with stepwise increases in FPG and insulin and reduced hepatic insulin sensitivity. KLF6 binds to the liver-specific Gck promoter and activates a GCK promoter-reporter, identifying GCK as a KLF6 direct transcriptional target. Accordingly, in DeltaKlf6 hepatocytes Gck expression was reduced and stable transfection of Klf6 led to up-regulation of Gck. GCK and KLF6 mRNAs correlate directly in human NAFLD tissues and immunohistochemistry studies confirm falling levels of both KLF6 and GCK in fat-laden hepatocytes. In contrast to full-length KLF6, splice variant KLF6-SV1 increases in NAFLD hepatocytes and inversely correlates with glucokinase regulatory protein, which negatively regulates GCK activity. CONCLUSION: KLF6 regulation of GCK contributes to the development of hepatic insulin resistance. The KLF6-IVS1-27A polymorphism, which generates more KLF6-SV1, combats this, lowering hepatic insulin resistance and blood glucose. PMID- 22095591 TI - Biodegradation of the ultraviolet filter benzophenone-3 under different redox conditions. AB - Biodegradation of the ultraviolet (UV) filter benzophenone-3 (BP-3) was investigated in the laboratory to understand its behavior and fate under oxic and anoxic (nitrate, sulfate, and Fe [III]-reducing) conditions. Biodegradation experiments were conducted in microcosms with 10% of activated sludge and digested sludge under oxic and anoxic conditions, respectively. Benzophenone-3 was well degraded by microorganisms under each redox condition. Under the redox conditions studied, the biodegradation half-life for BP-3 had the following order: oxic (10.7 d) > nitrate-reducing (8.7 d) > Fe (III)-reducing (5.1 d) > sulfate-reducing (4.3 d) >= anoxic unamended (4.2 d). The results suggest that anaerobic biodegradation is a more favorable attenuation mechanism for BP-3. Biodegradation of BP-3 produced two products, 4-cresol and 2,4 dihydroxybenzophenone, under oxic and anoxic conditions. Biotransformation of BP 3 to 2,4-dihydroxybenzophenone by way of demethylation of the methoxy substituent (O-demethylation) occurred in cultures under each redox condition. The further biotransformation of 2,4-dihydroxybenzophenone to 4-cresol was inhibited under oxic, nitrate-reducing, and sulfate-reducing conditions. PMID- 22095592 TI - Tissue engineering of cartilage using a mechanobioreactor exerting simultaneous mechanical shear and compression to simulate the rolling action of articular joints. AB - The effect of dynamic mechanical shear and compression on the synthesis of human tissue-engineered cartilage was investigated using a mechanobioreactor capable of simulating the rolling action of articular joints in a mixed fluid environment. Human chondrocytes seeded into polyglycolic acid (PGA) mesh or PGA-alginate scaffolds were precultured in shaking T-flasks or recirculation perfusion bioreactors for 2.5 or 4 weeks prior to mechanical stimulation in the mechanobioreactor. Constructs were subjected to intermittent unconfined shear and compressive loading at a frequency of 0.05 Hz using a peak-to-peak compressive strain amplitude of 2.2% superimposed on a static axial compressive strain of 6.5%. The mechanical treatment was carried out for up to 2.5 weeks using a loading regime of 10 min duration each day with the direction of the shear forces reversed after 5 min and release of all loading at the end of the daily treatment period. Compared with shaking T-flasks and mechanobioreactor control cultures without loading, mechanical treatment improved the amount and quality of cartilage produced. On a per cell basis, synthesis of both major structural components of cartilage, glycosaminoglycan (GAG) and collagen type II, was enhanced substantially by up to 5.3- and 10-fold, respectively, depending on the scaffold type and seeding cell density. Levels of collagen type II as a percentage of total collagen were also increased after mechanical treatment by up to 3.4-fold in PGA constructs. Mechanical treatment had a less pronounced effect on the composition of constructs precultured in perfusion bioreactors compared with perfusion culture controls. This work demonstrates that the quality of tissue-engineered cartilage can be enhanced significantly by application of simultaneous dynamic mechanical shear and compression, with the greatest benefits evident for synthesis of collagen type II. PMID- 22095593 TI - Supramolecular inclusion complexes of two cyclic zinc bisporphyrins with C60 and C70: structural, thermodynamic, and photophysical characterization. AB - The formation of thermodynamically stable inclusion complexes between two cyclic zinc bisporphyrins, differing in the saturation degree of the hydrocarbon linkers that connect their porphyrin units, and the fullerenes C(60) and C(70) is described. Binding and photophysical studies were performed in two solvents of very different polarity: toluene and dichloromethane. UV/Vis and fluorescence titration experiments showed pi-pi interactions between the cyclic zinc bisporphyrins and the fullerenes. Solid-state structures were determined by X-ray diffraction analysis and gave valuable insight into the different complexation behaviors of the two macrocyclic systems towards the fullerenes. NMR titrations were also helpful in understanding the geometry of the complexes in solution. Upon fullerene complexation, the two macrocyclic bisporphyrins adopt very distinct conformations. Charge-transfer absorption bands point to ground-state interactions, and quenching of the porphyrin component luminescence indicates fast reactivity in the excited states. Energy transfer plus HOMO-HOMO and LUMO LUMO electron-transfer processes occur within the complexes. Charge-separated states characterized by a reduced fullerene and an oxidized porphyrin radical, with lifetimes in the order of several hundred picoseconds, are detected. PMID- 22095595 TI - Environmental and genetic factors affecting the weaning-estrus interval in sows. AB - We examined the effects of environmental and genetic factors on the weaning-to estrus interval (WEI) in sows. In order to perform the analyses of the environmental factors, 8104 observations of the 1st to the 6th WEI were carried out, while 6548 observations of the 1st to the 3rd WEI were carried out for the analyses of genetic factors. The environmental model included as fixed effects, herd, genetic line, year and season of birth, as well as the covariates, age of sow at farrowing, litter size at birth and lactation length. Genetic analysis was performed by repeatability and multitrait models. The mean and coefficient of variation for WEI were 7.02 days and 100.6%, respectively. The linear effect of lactation length and the quadratic effect of the age of sow at farrowing affected the WEI. Herd, year and season of farrowing were significant sources of variation for WEI, and there was no influence of genetic line or of litter size at birth. Heritability estimated by the repeatability model was 0.04, while heritabilities obtained by the multitrait model were 0.07, 0.02 and 0.07 for the first three WEI, respectively. Estimates of genetic correlations among the different WEI were of moderate to low magnitude. It was concluded that environmental factors, such as year and season of farrowing, lactation length, age of sow at farrowing and herd, should be considered in the model for best estimation of genetic parameters for this trait. Although with only a small possible genetic gain, selection can be made based on the first WEI. PMID- 22095594 TI - The dual role of fragments in fragment-assembly methods for de novo protein structure prediction. AB - In fragment-assembly techniques for protein structure prediction, models of protein structure are assembled from fragments of known protein structures. This process is typically guided by a knowledge-based energy function and uses a heuristic optimization method. The fragments play two important roles in this process: they define the set of structural parameters available, and they also assume the role of the main variation operators that are used by the optimiser. Previous analysis has typically focused on the first of these roles. In particular, the relationship between local amino acid sequence and local protein structure has been studied by a range of authors. The correlation between the two has been shown to vary with the window length considered, and the results of these analyses have informed directly the choice of fragment length in state-of the-art prediction techniques. Here, we focus on the second role of fragments and aim to determine the effect of fragment length from an optimization perspective. We use theoretical analyses to reveal how the size and structure of the search space changes as a function of insertion length. Furthermore, empirical analyses are used to explore additional ways in which the size of the fragment insertion influences the search both in a simulation model and for the fragment-assembly technique, Rosetta. PMID- 22095597 TI - Clonal monosomy of chromosome 21 in a case of myelodysplastic syndrome. AB - This study reports on a cytogenetic finding in a bone marrow examination of a 47 year-old male patient treated in the Hematology and Blood Transfusion Service of the Hospital de Base in Sao Jose do Rio Preto, Sao Paulo State, Brazil. The only alteration found at diagnosis of myelodysplastic syndrome (MDS) subtype refractory anemia with excess blasts (RAEB-2) was clonal monosomy of chromosome 21. The patient evolved to acute myeloid leukemia type M2 and died nine months after diagnosis. Clonal monosomy of chromosome 21, as the only cytogenetic abnormality in MDS, has only been reported three times previously. This uncommon cytogenetic abnormality in MDS has been associated with a poor clinical course, although more data will be needed to determine if this prognosis is invariable. PMID- 22095596 TI - Lactic acid bacteria dynamics during spontaneous fermentation of cocoa beans verified by culture-independent denaturing gradient gel electrophoresis. AB - Cocoa is naturally fermented in the field before the cocoa seeds are removed for processing. We assessed the dynamics of lactic acid bacteria during cocoa fermentation in Bahia, Brazil. During five days of fermentation, temperature and pH were measured and beans were collected for genomic DNA extraction every 12 h. The DNA was used as a template for amplification with Lac1-Lac2 and Lac3-Lac2 for denaturing gradient gel electrophoresis analyses. pH values ranged from 3.34 to 4.98, while the temperature varied from 23 degrees to 50 degrees C. Lac1 Lac2 primers permitted detection of 11 operational taxonomic units. Twenty-eight operational taxonomic units were obtained with the primer pair Lac3-Lac2. It was observed that there were variations between the numbers of operational taxonomic units throughout the process, probably because of changes in pH and temperature. The greatest similarity in amplified samples was obtained with the primers Lac3 Lac2. PMID- 22095598 TI - A novel polymorphism of the myogenin gene is associated with body measurement traits in native Chinese breeds. AB - Using PCR-SSCP and DNA sequencing technology, we examined the association of single nucleotide polymorphisms (SNPs) in the bovine MyoG gene with body measurement traits in 779 individuals of six native Chinese cattle breeds, namely Luxi, Luxi * Simmental crossbred, Nanyang, Xia'nan, Jiaxian red, and Qinchuan. A novel SNP, T314C, was detected. Allelic frequencies of MyoG-T/C in the six breeds were 0.8308/0.1692, 0.8774/0.1226, 0.8021/0.1979, 0.8209/0.1791, 0.8630/0.1370, 0.8044/0.1956, respectively. Least squares analysis revealed a significant (P < 0.05) association of the MyoG SNP with rump length in four breeds (Luxi, Xia'nan, Jiaxian red, and Qinchuan), with hucklebone width in three breeds (Luxi * Simmental crossbred, Nanyang and Xia'nan), with waist height in two breeds (Luxi * Simmental crossbred and Nanyang) and with body length in the Luxi breed. We conclude that the MyoG SNP has potential as a genetic marker for economically relevant body measurement traits in native Chinese cattle breeds. PMID- 22095599 TI - Assessing molecular and morpho-agronomical diversity and identification of ISSR markers associated with fruit traits in quince (Cydonia oblonga). AB - Quince is a deciduous tree known to the countries around the Mediterranean since antiquity. Nowadays, quince is used as an ornamental plant, and as a rootstock for pear trees, with its fruit being appreciated mainly for production of jam and sweets rather than for raw consumption. Quince leaves contain compounds with antioxidant, antimicrobial and anticancerous properties that have been the focus of recent research on pharmaceutical and medical uses as well as for food preservatives. An orchard has been established in Greece, composed of quince varieties (Cydonia oblonga, N = 49) collected from different sites of the country (mainly from home gardens), constituting a unique quince gene bank collection for southeast Europe. We made a phenotypic analysis using 26 morphological plus seven agronomical descriptors coupled with molecular techniques in order to examine the genetic diversity within the collection. Principal component analysis using the 33 descriptors identified 10 components explaining the existence of more than 70% of the total variation. Subsequent cluster analysis classified most of the previously identified productive varieties of the quince orchard in the same clade of a dendrogram. Molecular analysis generated by 13 inter-simple sequence repeat primers amplified 139 bands, including 109 polymorphic bands, indicating a level of polymorphism of 79%; mean gene diversity was calculated to be 0.309. Using stepwise multiple regression analysis, a number of markers significantly associated with fire blight susceptibility, yield, mean fruit weight, citric acid content, soluble solid content, and fruit drop were identified. Hence, data extracted by multiple regression analysis could be useful in marker-assisted breeding programs, especially when no previous genetic information is available. PMID- 22095600 TI - AGPAT6 polymorphism and its association with milk traits of dairy goats. AB - As one of the eight members in the 1-acylglycerol-3-phosphate-O-acyltransferase (AGPATs) family, AGPAT6 is a crucial enzyme for the biosynthesis of glycerolipids and triacylglycerol in eukaryotes, as well as catalyzing the conversion from lysophosphatidic acid to phosphatidic acid. AGPAT6 can be considered as a candidate gene for regulating milk composition. DNA sequencing and PCR-RFLP methods were applied to detect genetic variation in the AGPAT6 gene in 549 Chinese dairy goats. Four polymorphisms (NC_007328.3:g.152G>C, 8124G>A, 9263C>G, 16436G>A) were detected in 5'UTR, intron 2, exon 4, and 3'UTR, respectively. For the KpnIota locus, the frequencies of the AGPAT6-G allele were 0.955 and 0.936 for SN (Xinong Sannen) and GZ (Guanzhong) dairy goat breeds, respectively. In the PCR-RFLP analysis for KpnIota, EcoRII, NcoIota, and BglIota, the frequencies of the G allele of AGPAT6 were 0.955 and 0.936, 0.694 and 0.819, 0.206 and 0.254, 0.729 and 0.623 for SN and GZ dairy goat breeds, respectively. The 9263C>G mutation revealed a synonymous genetic code of Thr (threonine). Associations between the four mutations and milk traits were analyzed in two dairy goat breeds. At the 9263C>G locus, genotype GG and CG individuals showed significantly better milk performance than genotype CC individuals (P < 0.05). Therefore, the G allele is suggested to be a molecular marker for milk production in dairy goats. PMID- 22095601 TI - Genomic DNA extraction from medicinal plants available in Malaysia using a TriOmic(TM) improved extraction kit. AB - DNA extraction was carried out on 32 medicinal plant samples available in Malaysia using the TriOmic(TM) extraction kit. Amounts of 0.1 g flowers or young leaves were ground with liquid nitrogen, lysed at 65 degrees C in RY1(plus) buffer and followed by RNAse treatment. Then, RY2 buffer was added to the samples and mixed completely by vortexing before removal of cell debris by centrifugation. Supernatants were transferred to fresh microcentrifuge tubes and 0.1 volume RY3 buffer was added to each of the transferred supernatant. The mixtures were applied to spin columns followed by a centrifugation step to remove buffers and other residues. Washing step was carried out twice by applying 70% ethanol to the spin columns. Genomic DNA of the samples was recovered by applying 50 MUL TE buffer to the membrane of each spin column, followed by a centrifugation step at room temperature. A modification of the TriOmic(TM) extraction procedure was carried out by adding chloroform:isoamyl alcohol (24:1) steps in the extraction procedure. The genomic DNA extracted from most of the 32 samples showed an increase of total yield when chloroform:isoamyl alcohol (24:1) steps were applied in the TriOmicTM extraction procedure. This preliminary study is very important for molecular studies of medicinal plants available in Malaysia since the DNA extraction can be completed in a shorter period of time (within 1 h) compared to manual extraction, which entails applying phenol, chloroform and ethanol precipitation, and requires 1-2 days to complete. PMID- 22095602 TI - Lack of an association between -308G>A polymorphism of the TNF-alpha gene and liver cirrhosis risk based on a meta-analysis. AB - TNF-alpha is a potential proinflammatory cytokine that plays an important role in the pathogenesis of liver cirrhosis. We investigated a possible association between TNF-alpha -308G>A polymorphism and liver cirrhosis risk by conducting a meta-analysis. Publications addressing the association between TNF-alpha -308G>A and liver cirrhosis risk were selected from the Pubmed and Embase databases. Data were extracted from the studies by two independent reviewers; odds ratio (OR) with a 95% confidence interval (CI) was calculated from these data. The meta-analysis was performed by Review Manager Version 5.0.24 and STATA Version 9.2. Eleven studies were retrieved, reporting a total of 1796 liver cirrhosis cases and 2113 healthy controls. A meta-analysis of these 11 studies identified no significant association between TNF-alpha -308G>A polymorphism and liver cirrhosis risk in all comparisons of G vs A allele; GG vs GA + AA; GG + GA vs AA; GG vs AA; GG vs GA (OR = 1.14, 95%CI = 0.85-1.55, P = 0.38; OR = 1.24, 95%CI = 0.87- 1.77, P = 0.24; OR = 0.90, 95%CI = 0.62-1.30, P = 0.57; OR = 1.03, 95%CI = 0.56-1.89, P = 0.92; OR = 1.30, 95%CI = 0.90-1.88, P = 0.17; respectively). In conclusion, we found no association between TNF-alpha -308G>A polymorphism and liver cirrhosis risk, both in Caucasian and Asian populations. PMID- 22095603 TI - Population structure and demographic inferences concerning the endangered onychophoran species Epiperipatus acacioi (Onychophora: Peripatidae). AB - Epiperipatus acacioi (Onychophora: Peripatidae) is an endemic species of the Atlantic rainforest in southeastern Brazil, with a restricted known distribution, found only in two nearby areas (Tripui and Itacolomi). Mitochondrial gene COI sequences of 93 specimens collected across the known range of E. acacioi were used to assess the extant genetic diversity and patterns of genetic structure, as well as to infer the demographic history of this species. We found considerable variability within the populations, even though there has been recent environmental disturbance in these habitats. The samples from the two areas where this species is found showed significantly different COI sequences and constitute two distinct populations [exact test of sample differentiation (P = 0.0008) and pairwise F(ST) analyses (F(ST) = 0.214, P < 0.00001)]. However, there was little genetic differentiation among samples from different sampling sites within populations, suggesting that the potential for dispersal of E. acacioi greater than would have been expected, based on their cryptic behavior and reduced vagility. Mismatch analyses and neutrality tests revealed evidence of recent population expansion processes for both populations, possibly related to variations in the past distribution of this species. PMID- 22095604 TI - Molecular differentiation of species of the genus Zungaro (Siluriformes, Pimelodidae) from the Amazon and Parana-Paraguay River basins in Brazil. AB - Fish species of the Zungaro genus (Siluriformes, Pimelodidae) are amongst the largest migratory fish in Latin America and have considerable economic importance for commercial fishing in Brazil. However, natural populations of this large catfish are experiencing a severe decline. There are significant taxonomical inconsistencies for this fish. Two geographically separated species of the fish were initially described, one endemic in the Amazon and another in the Parana-Paraguay River basins. A taxonomic review had recently proposed that there is only one Zungaro species in Brazil, based on morphological data. We made a molecular study of Zungaro populations in an attempt to solve taxonomical inconsistencies and to analyze genetic diversity in natural populations of this genus. We analyzed two regions of the mitochondrial DNA (the control region and the ATPase 6 gene region) of individuals sampled from the Parana-Paraguay River and Amazon River basins. Analyses based on p-distances and maximum likelihood phylogenetic models showed a genetic difference between populations corresponding to different species. Genetic differentiation between Zungaro populations was at the same level as that observed between other Siluriformes species, using the same DNA sequences. We conclude that Zungaro species of the Parana-Paraguay River basin do not belong to the same species found in the Amazon basin. This finding has a significant implication for conservation of this fish, given that populations are disappearing at a high rate in the Parana Paraguay River basin, mainly due to impoundments. PMID- 22095605 TI - Molecular authentication of the medicinal herb Ruta graveolens (Rutaceae) and an adulterant using nuclear and chloroplast DNA markers. AB - Dried parts of different plant species often look alike, especially in powdered form, making them very difficult to identify. Ruta graveolens, sold as a dried medicinal herb, can be adulterated with Euphorbia dracunculoides. The genomic DNA was isolated from the leaf powder (100 mg each) using the modified CTAB method. Internal transcribed spacer sequences of nuclear ribosomal DNA (nrDNA ITS), and chloroplast spacer sequences (rpoB and rpoC1) are regarded as potential genes for plant DNA barcoding. We amplified and sequenced these spacer sequences and confirmed the sequences with a BLAST search. Sequence alignment was performed using ClustalX to look for differences in the sequences. A DNA marker was developed based on rpoB and rpoC1 of the nrDNA-ITS for the identification of the adulterant E. dracunculoides in samples of R. graveolens that are sold in local herbal markets. Sequence-characterized amplified region markers of 289 and 264 bp for R. graveolens and 424 bp for E. dracunculoides were developed from dissimilar sequences of this nrDNA-ITS to speed up the authentication process. This marker successfully distinguished these species in extracted samples with as little as 5 ng DNA/MUL extract. PMID- 22095606 TI - Aluminum triggers broad changes in microRNA expression in rice roots. AB - MicroRNAs are small 21-nucleotide RNA molecules with regulatory roles in development and in response to stress. Expression of some plant miRNAs has been specifically associated with responses to abiotic stresses caused by cold, light, iron, and copper ions. In acid soils, aluminum solubility increases, thereby causing severe damage to plants. Although physiological aspects of aluminum toxicity in plants have been well characterized, the molecular mediators are not fully elucidated. There have been no reports about miRNA responses to aluminum stress. Modulation of miRNA expression may constitute a key element to explain the mechanisms implicated in aluminum toxicity and tolerance. We examined the expression of at least one miRNA member from each miRNA family in rice roots of Oryza sativa spp indica cv. Embrapa Taim and Oryza sativa spp japonica cv. Nipponbare under high concentrations of aluminum. Forty six miRNA families were effectively detected by quantitative PCR. Among these, 13 were down-regulated and six were up-regulated in roots of the Nipponbare cultivar after 8 h of aluminum treatment. In roots of the Embrapa Taim cultivar, five miRNAs were down-regulated and three were up-regulated. Analyses of their putative targets suggest that these rice miRNAs are involved in the regulation of various metabolic pathways in response to high concentrations of aluminum. PMID- 22095607 TI - Association between a single nucleotide polymorphism in the bovine chemerin gene and carcass traits in Qinchuan cattle. AB - Qinchuan is a red or yellow draft and beef breed in China. In order to identify a predictor of carcass traits on the basis of associations between carcass traits and gene polymorphism, variation in the bovine chemerin gene was investigated using PCR-single-strand conformational polymorphism and DNA sequencing. An SNP of A868G located in exon 2 of the Bos taurus chemerin gene was detected in 716 samples of six breeds (Jiaxian red, Luxi, Nan yang, Qinchuan, Simmental and Luxi crossbred steers, and Xia'nan), all in China, and three genotypes (AA, AG and GG) were found. Based on the chi(2) test, the AA/AG/GG genotype frequencies of all six breeds were found to be in Hardy Weinberg equilibrium. A possible association of A868G with some carcass traits was investigated in 106 Qinchuan cattle. Animals with the AG genotype were found to have significantly lower mean loin eye area and meat tenderness compared to those with the AA and GG genotypes. However, there was no significant association between any individual haplotype and backfat thickness, water holding capacity or marbling score. We suggest that A868G could be used as a molecular marker in marker-assisted selection for carcass traits. PMID- 22095608 TI - Lack of association between RANTES-28, SDF-1 gene polymorphisms and systemic lupus erythematosus in the Malaysian population. AB - Regulated on activation, normal T-cell expressed and secreted (RANTES) and stromal cell-derived factor 1 (SDF-1) are members of the CC- and CXC-chemokine families, respectively. Both genes have been postulated to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We analyzed position 28 of the RANTES gene promoter region, as well as the SNP observed in the 3' UTR of the SDF-1 gene at position 801, in 130 patients presenting SLE at the Malaya University Medical Centre. Screening of 130 healthy volunteer controls using RFLP was also performed. RANTES-28 polymorphism analysis showed no significant (P = 0.3520) relationship, even though homozygous C/C was more frequent in SLE patients (OR = 1.4183) and heterozygous C/G was more frequent in healthy controls (OR = 0.7051). There were no significant (P = 0.2650) associations between A/A (OR = 0.783), G/G (OR = 1.5914) and G/A (OR = 0.8289) genotypes in the SDF-1 gene polymorphism with SLE. We conclude that there is no significant association of RANTES-28 and SDF-1 gene polymorphisms and occurrence of SLE in Malaysia. PMID- 22095609 TI - Multiple displacement amplification for preimplantation genetic diagnosis of fragile X syndrome. AB - Preimplantation genetic diagnosis (PGD) has become an assisted reproductive technique for couples that have genetic risks. Despite the many advantages provided by PGD, there are several problems, including amplification failure, allele drop-out and amplification inefficiency. We evaluated multiple displacement amplification (MDA) for PGD of the fragile X syndrome. Whole genome amplification was performed using MDA. MDA products were subjected to fluorescent PCR of fragile X mental retardation-1 (FMR1) CGG repeats, amelogenin and two polymorphic markers. In the pre-clinical tests, the amplification rates of the FMR1 CGG repeat, DXS1215 and FRAXAC1 were 84.2, 87.5 and 75.0%, respectively, while the allele dropout rates were 31.3, 57.1 and 50.0%, respectively. In two PGD treatment cycles, 20 embryos among 30 embryos were successfully diagnosed as 10 normal embryos, four mutated embryos and six heterozygous carriers. Three healthy embryos were transferred to the uterus; however, no clinical pregnancy was achieved. Our data indicate that MDA and fluorescent PCR with four loci can be successfully applied to PGD for fragile X syndrome. Advanced methods for amplification of minuscule amounts of DNA could improve the sensitivity and reliability of PGD for complicated single gene disorders. PMID- 22095610 TI - Evaluation of a hydrogel based breast biopsy marker (HydroMARK(r)) as an alternative to wire and radioactive seed localization for non-palpable breast lesions. AB - BACKGROUND AND OBJECTIVES: HydroMARK(r) is a newly available biopsy marker for image-guided needle biopsies of non-palpable breast lesions. Objective was to determine if the marker could be utilized independently for lesion localization using intra-operative ultrasound alone. METHODS: A single institution retrospective review identified patients who underwent surgical excision of breast lesions after placement of the HydroMARK(r). Endpoints included intra operative visualization of the marker, successful excision of the lesion, and presence of the marker on specimen radiograph. RESULTS: The study included 31 lesions in 25 patients. Twenty-nine (93.6%) HydroMARKSs(r) were adequately visualized by intra-operative ultrasound. Intra-operative ultrasound without pre operative placement of a localizing device was successful for localization in six cases (19.4%). Intra-operative difficulties were encountered in 16 of 31 (51.6%) procedures. This included either extrusion of the marker when the biopsy tract was transected in 14 (45.2%) cases or migration of the marker prior to the procedure in two (6.4%) cases. The marker was visualized on specimen radiograph in 15 (48.4%) cases. CONCLUSIONS: While intraoperative sonographic visibility was excellent, a large number of excisions were associated with extrusion of the marker. Modifications are needed to improve acceptability of this marker for intra-operative localization independent of pre-operative wire or seed localization. PMID- 22095611 TI - PlexinA2 mediates osteoblast differentiation via regulation of Runx2. AB - The imbalance between bone-resorbing osteoclasts and bone-forming osteoblasts often leads to bone destructive diseases such as osteoporosis. In contrast to the development of several antiresorptive agents for osteoporosis therapy, discovery of anabolic drugs has been difficult because of an insufficient understanding of the complex mechanism of bone formation. In a microarray analysis with mouse preosteoblast cells, we found that PlexinA2 (PlxnA2), a molecule previously known to mediate axon guidance in neural development, was upregulated by the osteogenic factor BMP2. PlxnA2-specific siRNA decreased Runx2 expression, osteoblast differentiation, and mineralization. Runx2 overexpression restored osteoblastic differentiation of PlxnA2-knockdown cells. PlxnA2 was associated with both type 1 and 2 BMP receptors, and BMP2 increased the interaction between PlxnA2 and type 1 receptors. PlxnA2 also affected Smad and Akt signaling pathways downstream of BMP2. Taken together, the results of our study reveal that PlxnA2 has a pro osteogenic function by modulating BMP2 signaling. Therefore, PlxnA2 may be a useful target for development of bone anabolic therapeutics. PMID- 22095612 TI - Sex differences in repetitive stereotyped behaviors in autism: implications for genetic liability. AB - The implications of the well known sex differences in the prevalence of autism spectrum disorder (ASD) are not well understood. The aim of this paper was to investigate whether these differences might be associated with differences in genetic liability. Individuals with ASD (970 families, 2,028 individuals) were recruited as part of the Autism Genome Project (AGP). The families were differentiated into families containing a female (either female-female or male female) and those with only males. If the sex with the lower prevalence is associated with a greater genetic liability necessary to cross sex-specific thresholds, the males from female containing families should be more severely affected than males from male only families. Affected subjects from the different types of families with ASD were sampled and compared on the social reciprocity and repetitive behavior scores from the Autism Diagnostic Interview-Revised (ADI R). In general, females had lower repetitive behavior scores than males. More importantly, males from female containing families had higher repetitive behavior scores than males from male-male families. No such differences were apparent on the social reciprocity scores. These results support the hypothesis of a multiple threshold model of genetic liability of ASD with females having a higher liability for affectation status, at least on the repetitive behavior dimension of the disorder. These data also support the dissociation of the different phenotypic dimensions of ASD in terms of its genetic architecture. The implications of these results for linkage and association studies are discussed. PMID- 22095613 TI - 1H-magnetic resonance spectroscopy of the breast at 3.0-T: comparison of results obtained before and after administration of gadolinium-based contrast agent. AB - PURPOSE: To assess the effects of gadolinium-based contrast agent (GBCA) on (1) H magnetic resonance spectroscopy (MRS) of the breast at 3.0-T. MATERIALS AND METHODS: Patients (n = 98) with breast cancer (98 lesions) underwent MRS (point resolved spectroscopy sequence [PRESS]; TR/TE, 2000/100 msec; voxel size, 15 * 15 * 15 mm) before the administration of GBCA. In 52 of those patients, MRS was also performed after the administration of GBCA. The voxel-of-interest (VOI) was placed by referring to the noncontrast-enhanced MRI (diffusion-weighted images combined with fat-suppressed T2-weighted images). We reviewed and graded the appropriateness of VOI location compared to the correlating enhancement lesions. Integral values of the choline peak at a frequency of 3.2 ppm on MRS were compared before and after the administration of GBCA. RESULTS: The VOI was placed correctly in 64 lesions (65%), although the VOI was placed outside the targeted lesion in 34 lesions (35%). The integral value of the choline peak on MRS decreased significantly after the administration of GBCA (P < 0.001). CONCLUSION: Accumulation of GBCA in breast cancer could affect the choline peak on MRS. MRS of breast cancer at 3.0-T can be recommended to be acquired before contrast enhanced study; however, some problems remain in VOI placement with reference to the noncontrast-enhanced study. PMID- 22095614 TI - Development of the human corpus striatum and the presence of nNOS and 5-HT2A receptors. AB - This study focussed on the development of the corpus striatum in the fetus, using silver impregnation and immunohistochemistry. For the latter, we looked for nNOS positive cells and 5-HT(2A) receptors positive cells in the corpus striatum during development. During the initial formation of the corpus striatum, there was migration cells of the ganglionic eminence toward the putamen by 15-17 weeks of gestation. Process formation in the neurons started by week 17 and became very complex before term (31/32 weeks of gestation). By 25-27 gestational weeks, the globus pallidus already had two parts and the corpus striatum was similar to the adult in configuration. The nNOS positive cells appeared early (21-23 weeks in gestation) while 5-HT(2A) receptors positive cells were not observed until 31/32 weeks gestation. The number of positive cells in both groups was relatively small. It is anticipated that further developmental changes would occur in the postnatal/neonatal phases. PMID- 22095615 TI - Lipid nanoparticle siRNA systems for silencing the androgen receptor in human prostate cancer in vivo. AB - The androgen receptor (AR) plays a critical role in the progression of prostate cancer. Silencing this protein using short-hairpin RNA (shRNA) has been correlated with tumor growth inhibition and decreases in serum prostate specific antigen (PSA). In our study, we have investigated the ability of lipid nanoparticle (LNP) formulations of small-interfering RNA (siRNA) to silence AR in human prostate tumor cell lines in vitro and in LNCaP xenograft tumors following intravenous (i.v.) injection. In vitro screening studies using a panel of cationic lipids showed that LNPs containing the ionizable cationic lipid 2,2 dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-KC2-DMA) exhibited the most potent AR silencing effects in LNCaP cells. This is attributed to an optimized ability of DLin-KC2-DMA-containing LNP to be taken up into cells and to release the siRNA into the cell cytoplasm following endocytotic uptake. DLin-KC2 DMA LNPs were also effective in silencing the AR in a wild-type AR expressing cell line, LAPC-4, and a variant AR expressing cell line, CWR22Rv1. Importantly, it is demonstrated that LNP AR-siRNA systems containing DLin-KC2-DMA can silence AR gene expression in distal LNCaP xenograft tumors and decrease serum PSA levels following i.v. injection. To our knowledge, this is the first report demonstrating the feasibility of LNP delivery of siRNA for silencing AR gene expression in vivo. PMID- 22095616 TI - Predictors of clinical efficacy of 'Ablate and Pace' therapy in patients with permanent atrial fibrillation. AB - OBJECTIVE: To evaluate the 2-year clinical improvement after 'Ablate and Pace' therapy and to identify the variables able to influence the efficacy of this therapy in patients with permanent atrial fibrillation (AF). Design Prospective multicentre observational study. Setting Cardiology departments of 19 general hospitals in Italy, Spain and Greece. PATIENTS: 171 patients with drug-refractory severely symptomatic permanent AF considered for AV junction ablation. Interventions Patients underwent AV junction ablation, received a right ventricular (RV) pacing or echo-guided cardiac resynchronisation (CRT) pacing and were followed-up to 24 months. Main outcome measures Non-responders to Ablate and Pace therapy were defined those patients who, during the follow-up period had clinical failure (defined as death or hospitalisation due to heart failure, or worsening heart failure) or showed no improvement in their clinical condition. RESULTS: Responders were 63% of RV-paced patients and 83% of CRT-paced patients. Another 27% showed no clinical improvement (7%) or worsened (20%) (non-responders group). On multivariable Cox regression analysis, CRT mode and echo-optimised CRT were the only independent protective factors against non-response (HR=0.24, 95% CI 0.10-0.58, p=0.001 and HR=0.22, 95% CI 0.07-0.77, p=0.018 respectively). On comparing freedom from non-response, a trend in favour of echo-optimised CRT versus simultaneous biventricular pacing (p=0.077) was seen. CONCLUSIONS: In patients affected by severely symptomatic permanent AF, Ablate and Pace therapy yielded a clinical benefit in 63% of RV-paced patients and 83% of CRT-paced patients. CRT pacing and echo-optimised CRT were the only independent predictor of clinical benefit. PMID- 22095617 TI - Improvements in risk stratification for the occurrence of cardiovascular disease by imaging subclinical atherosclerosis: a systematic review. AB - CONTEXT: Imaging for subclinical atherosclerosis on top of conventional risk factor assessment may improve risk prediction for the occurrence of cardiovascular disease events in asymptomatic individuals. OBJECTIVE: To systematically review the available evidence on this issue. DATA SOURCES: PubMed MEDLINE was systematically searched on 7 September 2011. STUDY SELECTION: Studies were included that evaluated the added value of flow mediated dilation (FMD), carotid intima-media thickness (CIMT), carotid plaques and/or coronary artery calcification (CAC) scoring in the prediction of risk for developing fatal or non fatal cardiovascular events. DATA EXTRACTION: Data on general study characteristics and the added predictive performance of imaging markers in terms of discrimination, calibration and (re)classification were extracted. RESULTS: 25 studies were selected that provided information on added predictive value of FMD (n=2), CIMT (n=12), carotid plaques (n=6) and/or CAC (n=9). Heterogeneity existed across studies in the conventional risk models that were used and in the measurements of the imaging marker. The added predictive value, quantified by the difference in c-index, of FMD, CIMT, carotid plaques or CAC ranged from 0.00 to 0.01 for FMD, from 0.00 to 0.03 for CIMT, from 0.01 to 0.05 for carotid plaque and from 0.05 to 0.13 for CAC. The reported net reclassification improvement (NRI) by the imaging markers ranged from -1.4% to 12% for CIMT, 8% to 11% for carotid plaques, 14% to 25% for CAC and 29% for FMD). Although the definition of intermediate cardiovascular risk varied across studies, the NRI was the highest in those at intermediate cardiovascular risk. CONCLUSIONS: Published evidence on the added value of atherosclerosis imaging varies across the different markers, with limited evidence for FMD and considerable evidence for CIMT, carotid plaque and CAC. The added predictive value of additional screening may be primarily found in asymptomatic individuals at intermediate cardiovascular risk. Additional research in asymptomatic individuals is needed to quantify the cost effectiveness and impact of imaging for subclinical atherosclerosis on cardiovascular risk factor management and patient outcomes. PMID- 22095618 TI - Efficacy and safety of a routine invasive strategy in non-ST segment elevation acute coronary syndromes according to age: an illustration of the difficulty in using combined endpoints with different clinical significance. PMID- 22095619 TI - Family history of liver cancer and hepatocellular carcinoma. AB - Familial clustering of hepatocellular carcinoma (HCC) has been frequently reported in eastern Asiatic countries, where hepatitis B infection is common. Little is known about the relationship between family history of liver cancer and HCC in Western populations. We carried out a case-control study in Italy, involving 229 HCC cases and 431 hospital controls. Data on family history were summarized through a binary indicator (yes/no) and a family history score (FHscore), considering selected family characteristics. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, hepatitis B surface antigen, and/or anti-hepatitis C virus positivity. We also performed a meta-analysis on family history of liver cancer and liver cancer updated to April 2011 using random effects models. After adjustment for chronic infection with hepatitis B/C viruses, family history of liver cancer was associated with HCC risk, when using both the binary indicator (OR, 2.38; 95% CI, 1.01-5.58) and the FHscore, with increasing ORs for successive score categories. Compared to subjects without family history and no chronic infection with hepatitis B/C viruses, the OR for those exposed to both risk factors was 72.48 (95% CI, 21.92-239.73). In the meta analysis, based on nine case-control and four cohort studies, for a total of approximately 3,600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06-3.03). CONCLUSION: A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk. PMID- 22095620 TI - Mutagenesis studies of the beta I domain metal ion binding sites on integrin alphaVbeta3 ligand binding affinity. AB - Three divalent cation binding sites in the integrin beta I domain have been shown to regulate ligand binding and adhesion. However, the degree of ligand binding and adhesion varies among integrins. The alphaLbeta2 and alpha4beta7 integrins show an increase in ligand binding affinity and adhesion when one of their ADMIDAS (adjacent to MIDAS, or the metal ion-dependent adhesion site) residues is mutated. By contrast, the alpha2beta1, alpha5beta1, and alphaIIbbeta3 integrins show a decrease in binding affinity and adhesion when their ADMIDAS is mutated. Our study here indicated that integrin alphaVbeta3 had lower affinity when the ADMIDAS was mutated. By comparing the primary sequences of these integrin subunits, we propose that one residue associated with the MIDAS (beta3 Ala(252)) may account for these differences. In the beta1 integrin subunit, the corresponding residue is also Ala, whereas in both beta2 and beta7 integrin subunits, it is Asp. We mutated the beta3 residue Ala(252) to Asp and combined this mutant with mutations of one or two ADMIDAS residues. The mutant A252D showed reduced ligand binding affinity and adhesion. The ligand binding affinity and adhesion were increased when this A252D mutant was paired with mutations of one ADMIDAS residue. But when paired with mutations of two ADMIDAS residues the mutant nearly abolished ligand-binding ability, which was restored by the activating glycosylation mutation. Our study suggests that the variation of this residue contributes to the different ligand binding affinities and adhesion abilities among different integrin families. PMID- 22095621 TI - An efficient palladium catalyst system for the oxidative carbonylation of glycerol to glycerol carbonate. AB - Glycerol carbonate can be readily synthesized from the oxidative carbonylation of glycerol catalyzed by PdCl(2)(phen) (phen=1,10-phenanthroline) with the aid of CuI. High conversion (95 %) and selectivity (98 %) are achieved and the turnover frequency (TOF) reaches 455 h(-1). Furthermore, a new zeolite-Y-confined Pd catalyst, PdCl(2)(phen)@Y, has been successfully prepared by a ''flexible ligand'' method. The structure and composition of the heterogeneous catalyst have been characterized by atomic absorption spectroscopy, elemental analysis, N(2) sorption, XRD, FTIR, solid-state NMR, and X-ray photoelectron spectroscopy. This catalyst exhibits a comparable activity to its homogeneous counterpart and could be reused five times without significant decrease in activity. This is the most efficient heterogeneous system for synthesizing glycerol carbonate by the oxidative carbonylation of glycerol to date. PMID- 22095622 TI - A validated method for the simultaneous quantitation of bioactive alkaloid markers in the leaf ethanolic extract of Cissampelos sympodialis Eichl.: a phenological variation study. AB - INTRODUCTION: The leaf hydroalcoholic extract of Cissampelos sympodialis Eichl. (Menispermaceae) has shown promising activity in different animal models of asthma. Several alkaloids have been identified in the extract, including warifteine and methylwarifteine (bisbenzylisoquinoline), as well as milonine (morphinandienone). OBJECTIVE: To develop and validate an analytical method for the simultaneous quantitation of the bioactive markers of C. sympodialis hydroalcoholic leaf extract and to apply the method to a seasonal (phenological) study of the concentration of the alkaloid markers. METHODOLOGY: The method used reversed phase high performance liquid chromatography with UV detection and calibration by standard addition. Separation was achieved using a C18-column (250 * 4.6 mm, 5 um) and a mobile phase consisting of a mixture of 0.05% aqueous (Et)3NH2 (A):MeOH(B) in gradient mode at a flow rate of 1.0 mL/min. RESULTS: The method proved to be linear in the concentration range tested (2-100 ug/mL, r2 > 0,99), precise (RSD <= 15%), accurate (85-115%), selective and robust. Detection limits for warifteine, methyl-warifteine and milonine were 0.39, 1.10 and 1.77 ug/mL respectively. The highest concentration of total alkaloids (determined as the sum of the three alkaloids) in the hydroalcoholic extract of the leaves was 2.9 +/- 0.2 mg/g extract (n = 3), prior to fruit development. Both warifteine and methylwarifteine were detected in the total alkaloid fraction of the ripened fruits. CONCLUSION: The results demonstrated that significant variations in the concentration of the biomarkers occurred throughout the vegetative cycle. The lowest concentration of the alkaloids in the leaves coincided with their appearance in the ripened fruits. PMID- 22095623 TI - Time-resolved NMR spectroscopic studies of DNA i-motif folding reveal kinetic partitioning. PMID- 22095624 TI - Transplacental transfer of polychlorinated biphenyls and polybrominated diphenyl ethers in arctic beluga whales (Delphinapterus leucas). AB - This study found that arctic beluga whales (Delphinapterus leucas) transferred, on average, 11.4% (7.5 mg) and 11.1% (0.1 mg) of their polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) blubber burden to their near-term fetuses. A single physicochemical parameter, log K(OW), largely explained this transplacental transfer for PCBs (r(2) =0.79, p < 0.00001) and PBDEs (r(2) = 0.37, p = 0.007), with congeners having a log K(OW) < 6.5 preferentially transferred to the fetus. Blubber concentrations of 257 ng/g lipid weight (lw) PCBs and 3.8 ng/g (lw) PBDEs in beluga fetuses highlights the exposure to endocrine-disrupting compounds during a critical developmental stage. The implications of detecting these levels of legacy PCBs and the flame retardant PBDEs in unborn arctic beluga are unclear. PMID- 22095625 TI - Mechanism selection for regiocontrol in base-assisted, palladium-catalysed direct C-H coupling with halides: first approach for oxazole- and thiazole-4 carboxylates. AB - Both base-assisted non-concerted metallation-deprotonation (nCMD) and concerted metallation-deprotonation (CMD) have been identified as two potent operating mechanisms in palladium-catalysed direct C-H coupling of oxazole and thiazole-4 carboxylate esters with halides through base- and solvent-effect experiments. Novel C2- and C5-selective CMD direct arylation procedures in oxazole- and thiazole-4-carboxylate series were then designed by controlling the balance between electronic and steric factors. Notably, charge interactions between the palladium catalyst and substrate were identified as a parameter for controlling selectivity and reducing the impact of steric factors in the CMD reaction. PMID- 22095626 TI - Structural and binding studies of the C-terminal domains of yeast TFIIF subunits Tfg1 and Tfg2. AB - The general transcription factor TFIIF plays essential roles at several steps during eukaryotic transcription. While several studies have offered insights into the structure/function relationship in human TFIIF, much less is known about the yeast system. Here, we describe the first NMR structural and binding studies of the C-terminal domains (CTDs) of Tfg1 and Tfg2 subunits of Saccharomyces cerevisiae TFIIF. We used the program CS-ROSETTA to determine the three dimensional folds of these domains in solution, and performed binding studies with DNA and protein targets. CS-ROSETTA models indicate that the Tfg1 and Tfg2 C terminal domains have winged-helix architectures, similar to the human homologs. We showed that both Tfg1 and Tfg2 CTDs interact with double-stranded DNA oligonucleotides, and mapped the DNA binding interfaces using solution NMR. Tfg1 CTD, but not Tfg2-CTD, also binds to yeast FCP1, an RNA polymerase II-specific phosphatase, and we delineated the interaction surface with the CTD of FCP1. Our results provide insights into the structural basis of yeast TFIIF function and the differential roles of Tfg1 and Tfg2 subunits during transcription. PMID- 22095628 TI - Adiponectin pathway attenuates malignant mesothelioma cell growth. AB - Malignant mesothelioma (MM) is caused by exposure to asbestos. Because MM has a latency period, short survival time, and has a poor response to current therapeutic regimes, long-term preventive strategies are required to suppress the advance of pathological states after asbestos exposure. Accumulating evidence suggests that adiponectin plays a crucial role in the regulation of energy metabolism by increasing AMP-activated protein kinase (AMPK) activation. Several studies have indicated that the activation of AMPK decreases cyclooxygenase (COX) 2 expression. Because high COX-2 levels correlated with a worse prognosis and survival rate in MM, we examined whether the adiponectin pathway suppresses MM cell growth through the AMPK/COX-2 pathway. In vivo, dietary fish oil (a potential promoter of adiponectin) decreased the growth rate of MM, which was accompanied by an increase in adiponectin and phospho-AMPK levels, and a decrease in COX-2 level. In vitro, adiponectin significantly impaired the cell proliferation rate of MM cell lines. These effects partly involved induction of growth arrest and apoptosis to MM cells. MM cells expressed both adiponectin receptors 1 and 2 (AdipoR1 and -R2) at mRNA and proteins levels. These receptors were functional, because adiponectin activated AMPK. Adiponectin treatment also significantly down-regulated protein levels of COX-2 and its downstream prostaglandin E(2). Finally, inhibitory analysis of AdipoR1/R2 by small interfering RNA knockdown suggests that adiponectin enhances AMPK activity and impairs the cell proliferation rate of MM cells, mainly via AdipoR1. These findings suggest that the induction or supplementation of adiponectin is an important tactic for developing therapeutic strategies against MM. PMID- 22095627 TI - Hyperoxia-induced LC3B interacts with the Fas apoptotic pathway in epithelial cell death. AB - Epithelial cell death plays a critical role in hyperoxia-induced lung injury. We investigated the involvement of the autophagic marker microtubule-associated protein-1 light chain-3B (LC3B) in epithelial cell apoptosis after hyperoxia. Prolonged hyperoxia (>95% O(2)), which causes characteristic lung injury in mice, activated morphological and biochemical markers of autophagy. Hyperoxia induced the time-dependent expression and conversion of LC3B-I to LC3B-II in mouse lung in vivo and in cultured epithelial cells (Beas-2B, human bronchial epithelial cells) in vitro. Hyperoxia increased autophagosome formation in Beas-2B cells, as evidenced by electron microscopy and increased GFP-LC3 puncta. The augmented LC3B level after hyperoxia was transcriptionally regulated and dependent in part on the c-Jun N-terminal kinase pathway. We hypothesized that LC3B plays a regulatory role in hyperoxia-induced epithelial apoptosis. LC3B siRNA promoted hyperoxia induced cell death in epithelial cells, whereas overexpression of LC3B conferred cytoprotection after hyperoxia. The autophagic protein LC3B cross-regulated the Fas apoptotic pathway by physically interacting with the components of death inducing signaling complex. This interaction was mediated by caveolin-1 tyrosine 14, which is a known target of phosphorylation induced by hyperoxia. Taken together, hyperoxia-induced LC3B activation regulates the Fas apoptotic pathway and thus confers cytoprotection in lung epithelial cells. The interaction of LC3B and Fas pathways requires cav-1. PMID- 22095629 TI - Six common errors cause dangerous mistakes in interpretation of electron micrographs. AB - The highly complex techniques of electron microscopy made it bound to the sensitive and critical micrograph analysis. The accurately interpreted micrographs are of paramount values in basic investigations. Interpretation skills and quality of the micrographs are the two fundamental keys in accomplishment of these goals but there are many mistakes and errors that can happen during the sample preparation, sectioning, EM operation, and photo publishing. The mentioned mistakes and errors effect directly in the final result which is a micrograph and can lead the analyzer who can be a pathologist to an interpretation followed by serious danger for patient. Artifacts caused by any given stimuli expected to be bothersome for investigators. Even best qualified equipments can be regarded as source of artifact generation. In this article, seven serious errors in electron micrographs which usually occur in transmission electron microscopy are addressed. PMID- 22095630 TI - Fluorescence detection of single-nucleotide polymorphism with single-strand triplex-forming DNA probes. AB - Triple-helix-forming oligonucleotides (TFOs) are widespread in the genome and have been found in regulatory regions, especially in promoter zones and recombination hotspots of DNA. To specifically detect these polypurine sequences, we designed and synthesized two dual pyrene-labeled single-strand oligonucleotide probes (TFO-FPs) consisting of recognition, linker, and detection sequences. The hybridization processes of TFO-FPs with target polypurine oligonucleotides involve both Watson-Crick and Hoogsteen base-pairings. Through double sensing of oligonucleotide sequences, single mutations of target oligonucleotides are detected by monitoring changes in pyrene fluorescence. The high specificities of the probes are maintained over a wide temperature range without sacrifice of hybridization kinetics. PMID- 22095632 TI - Reconsideration of the autonomic cranial ganglia: an immunohistochemical study of mid-term human fetuses. AB - The cranial parasympathetic ganglia have been reported to paradoxically contain the sympathetic nerve marker, tyrosine hydroxylase (TH), in addition to neurons expressing parasympathetic markers such as vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS). However, the distribution of these molecules in the cranial ganglia of human fetuses has not yet been examined. Using paraffin sections from 10 mid-term human fetuses (12-15 weeks), we performed immunohistochemistry for TH, VIP, and nNOS in the parasympathetic ciliary, pterygopalatine, otic, and submandibular ganglia, and for comparison, the sensory inferior vagal ganglion. The ciliary and submandibular ganglia contained abundant TH-positive neurons. In the former, TH-positive neurons were much more numerous than nNOS-positive neurons, whereas in the latter, nNOS immunoreactivity was extremely strong. No or a few cells in the pterygopalatine, otic, and inferior vagal ganglia expressed TH. Ciliary TH neurons appeared to compensate for classically described sympathetic fibers arising from the superior cervical ganglion, whereas in the submandibular ganglion, nNOS-positive neurons as well as TH neurons might innervate the lingual artery in addition to the salivary glands. Significant individual variations in the density of all these markers suggested differences in sensitivity to medicine affecting autonomic nerve function. Consequently, in the human cranial autonomic ganglia, it appears that there is no simple dichotomy between sympathetic and parasympathetic function. PMID- 22095631 TI - Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. AB - Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < -2.5 and not < 4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%-61%] and 51% [95% CI: 39%-66%] accounted for by percent change at month 36 and change in time dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% - >100%] and 72% [95% CI: 24% - >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab. PMID- 22095633 TI - Decreased expression of V-set and immunoglobulin domain containing 1 (VSIG1) is associated with poor prognosis in primary gastric cancer. AB - BACKGROUND: To date, the significance of altered expression of V-set and immunoglobulin domain containing 1 (VSIG1) in gastric cancer has not yet been elucidated. METHODS: We examined VSIG1 expression in 30 paired gastric cancer tissues and noncancerous gastric mucosa as well as in 5 gastric cancer cell lines by real-time PCR and Western blotting. In addition, we analyzed VSIG1 expression in 232 gastric adenocarcinoma samples by immunohistochemistry. RESULTS: VSIG1 expression was significantly reduced at both the mRNA and protein levels in gastric cancer tissues. Immunohistochemistry revealed that VSIG1 expression was completely lost in 126 out of the 232 (54.3%) patient samples and remarkably reduced in another 106 (45.7%) patients. Negative VSIG1 expression was significantly correlated with tumor size (P = 0.007), T (P = 0.023), and M stage (P = 0.037). Importantly, loss of VSIG1 expression was significantly correlated with poor overall survival (OS, P < 0.001) and disease-free survival (DFS, P = 0.006) in gastric cancer patients. Cox regression analyses showed that VSIG1 expression was an independent predictor of OS (P = 0.002) and DFS (P = 0.039). CONCLUSIONS: Our findings suggest that silencing VSIG1 may play an important role in gastric carcinogenesis and that VSIG1 may serve as a prognostic marker as well as a potential therapeutic target for gastric cancer. PMID- 22095634 TI - Statistical process control in nursing research. AB - In intervention studies in which randomization to groups is not possible, researchers typically use quasi-experimental designs. Time series designs are strong quasi-experimental designs but are seldom used, perhaps because of technical and analytic hurdles. Statistical process control (SPC) is an alternative analytic approach to testing hypotheses about intervention effects using data collected over time. SPC, like traditional statistical methods, is a tool for understanding variation and involves the construction of control charts that distinguish between normal, random fluctuations (common cause variation), and statistically significant special cause variation that can result from an innovation. The purpose of this article is to provide an overview of SPC and to illustrate its use in a study of a nursing practice improvement intervention. PMID- 22095635 TI - Aortic flow patterns in patients with Marfan syndrome assessed by flow-sensitive four-dimensional MRI. AB - PURPOSE: To apply time-resolved three-dimensional (3D) phase contrast MRI with three-directional velocity encoding (flow-sensitive 4D MRI) for the characterization of flow pattern changes in patients with Marfan syndrome (MFS) compared with normal controls. MATERIALS AND METHODS: Flow-sensitive 4D MRI of the thoracic aorta (temporal resolution ~45 ms, spatial resolution ~2.4 * 2.1 * 2.8 mm(3) ) was performed in 24 MFS patients and 10 volunteers. Aortic flow patterns were visualized by 3D particle traces and streamlines. Global (affecting the complete lumen) and local (parts of the vessel lumen) helix and vortex flow in the ascending aorta (AAo), aortic arch, and descending aorta (DAo) were graded in 3 categories (blinded reading, two observers): none = 0, moderate = 1, pronounced = 2. RESULTS: Flow grading revealed similar global helix and vortex flow in the AAo and arch for MFS patients and controls. Local helix flow in the AAo was significantly (P = 0.011) increased in patients and was associated with aortic sinus dilatation. The incidence of global helix and vortex flow in the DAo was increased in patients (77% and 50% of subjects) compared with controls (none and 10%). CONCLUSION: The 4D flow analysis revealed marked differences of the aortic flow patterns between Marfan patients and controls: Local helix flow in the patients' AAo may be associated with the increased incidence of aortic root dilatation. The flow alterations in the proximal DAo could explain the occurrence of Type-B dissection originating from this site. PMID- 22095637 TI - Myoinhibitory peptides in the brain of the cockroach Leucophaea maderae and colocalization with pigment-dispersing factor in circadian pacemaker cells. AB - Myoinhibitory peptides (MIPs) are a family of insect W(X(6))Wamides with inhibitory effects on visceral muscles and juvenile hormone synthesis. Although MIPs are widely distributed within the nervous system, a detailed analysis of their distribution and function in insect brains is still missing. We analyzed the distribution of MIPs in the brain of the cockroach Leucophaea maderae. We focused on the accessory medulla (AMe), a small neuropil near the medulla that acts as the master circadian clock. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and Nano-LC electrospray ionization (ESI) mass spectrometry revealed five Lem-MIPs in preparations of the AMe and corpora cardiaca. The complete sequences of two of these peptides were identified. Immunocytochemistry revealed wide distribution of MIP-related peptides in the cockroach brain. The superior median protocerebrum, parts of the central complex, and the tritocerebrum showed particularly dense immunostaining. In contrast, only a few local interneurons were stained in the antennal lobe and a few extrinsic neurons in the mushroom body, including a giant neuron innervating the calyces. The noduli of the AMe showed dense immunostaining, and neurons in all AMe cell groups except the anterior neurons were labeled. Pigment-dispersing factor- (PDF) and MIP immunostaining was colocalized in two neurons of the AMe. No colocalization of MIP- and PDF immunostaining was detected in the anterior optic commissure, but two small PDF-immunoreactive commissural fibers near the posterior optic commissure showed colocalized MIP immunostaining. The results suggest that several MIPs participate in different functional circuits of the circadian system and are involved in multiple brain circuits of the Madeira cockroach. PMID- 22095636 TI - Murine double minute 2 regulates Hu antigen R stability in human liver and colon cancer through NEDDylation. AB - Hu antigen R (HuR) is a central RNA-binding protein regulating cell dedifferentiation, proliferation, and survival, which are well-established hallmarks of cancer. HuR is frequently overexpressed in tumors correlating with tumor malignancy, which is in line with a role for HuR in tumorigenesis. However, the precise mechanism leading to changes in HuR expression remains unclear. In the liver, HuR plays a crucial role in hepatocyte proliferation, differentiation, and transformation. Here, we unraveled a novel mean of regulation of HuR expression in hepatocellular carcinoma (HCC) and colon cancer. HuR levels correlate with the abundance of the oncogene, murine double minute 2 (Mdm2), in human HCC and colon cancer metastases. HuR is stabilized by Mdm2-mediated NEDDylation in at least three lysine residues, ensuring its nuclear localization and protection from degradation. CONCLUSION: This novel Mdm2/NEDD8/HuR regulatory framework is essential for the malignant transformation of tumor cells, which, in turn, unveils a novel signaling paradigm that is pharmacologically amenable for cancer therapy. PMID- 22095638 TI - Implantable cardioverter defibrillator therapy in adults with congenital heart disease: who is at risk of shocks? AB - BACKGROUND: The value of implantable cardioverter defibrillators (ICDs) in adults with congenital heart disease (CHD) is unknown. We investigated the long-term outcome after ICD implantation and developed a simple risk stratification score for ICD therapy. METHODS AND RESULTS: A total of 136 adults with CHD and ICD (mean age+/-SD, 41+/-13 years; 67% male) were identified from 10 tertiary referral centers in the Netherlands and Belgium. The indication for ICD implantation was primary prevention in 50% of patients. Diagnoses included tetralogy of Fallot (51%), septal defects (20%), (congenitally corrected) transposition of the great arteries (13%), and other (16%). Thirty-nine patients (29%) received appropriate ICD shocks during a median follow-up of 4.6 years. Secondary prevention indication (hazard ratio [HR], 3.6; 95% CI, 1.3-9.5; P=0.009), coronary artery disease (HR, 2.7; 95% CI, 1.0-7.2; P=0.042), and symptomatic nonsustained ventricular tachycardia (NSVT; HR, 9.1; 95% CI, 2.8 29.2; P=0.001) were associated with appropriate ICD shocks. A risk score was developed to evaluate the likelihood of appropriate ICD shocks. The 8-year survival curve to first appropriate shocks was 94%, 57%, and 26% for low-, intermediate-, and high-risk patients, respectively. In primary prevention, symptomatic NSVTs (HR, 8.0; 95% CI, 2.3-27.1; P=0.001) and subpulmonary ventricular dysfunction (HR, 3.0; 95% CI, 1.2-12.6; P=0.02) were associated with appropriate shocks in univariable analysis. Inappropriate shocks occurred in 41 patients (30%). In addition, 40 patients (29%) experienced 45 implantation related complications. CONCLUSIONS: Adults with CHD and ICDs receive high rates of appropriate and effective shocks. Patients with secondary prevention indication, coronary artery disease, and symptomatic NSVT are at highest risk of receiving appropriate ICD shocks. ICD implantation is accompanied by considerable morbidity, including inappropriate shocks and procedure- related complications. PMID- 22095639 TI - The acute effects of changes to AV delay on BP and stroke volume: potential implications for design of pacemaker optimization protocols. AB - BACKGROUND: The AV delay optimization of biventricular pacemakers (cardiac resynchronization therapy) may maximize hemodynamic benefit but consumes specialist time to conduct echocardiographically. Noninvasive BP monitoring is a potentially automatable alternative, but it is unknown whether it gives the same information and similar precision (signal/noise ratio). Moreover, the immediate BP increment on optimization has been reported to decay away: it is unclear whether this is the result of an (undesirable) decrease in stroke volume or a (desirable) compensatory relief of peripheral vasoconstriction. METHODS AND RESULTS: To discriminate between these alternative mechanisms, we measured simultaneous beat-to-beat stroke volume (flow) using Doppler echocardiography, and BP using finger photoplethysmography, during and after AV delay changes from 40 to 120 ms in 19 subjects with cardiac pacemakers. BP and stroke volume both increased immediately (P<0.001, within 1 heartbeat). BP showed a clear decline a few seconds later (average rate, -0.65 mm Hg/beat; r=0.95 [95% CI, 0.86-0.98]); in contrast, stroke volume did not decline (P=0.87). The immediate BP increment correlated strongly with the stroke volume increment (r=0.74, P<0.001). The signal/noise ratio was 3-fold better for BP than stroke volume (6.8+/-3.5 versus 2.3+/-1.4; P<0.001). CONCLUSIONS: Improving AV delay immediately increases BP, but the effect begins to decay within a few seconds. Reassuringly, this is because of compensatory vasodilatation rather than reduction in cardiac function. Pacemaker optimization will never be reliable unless there is an adequate signal/noise ratio. Using BP rather than Doppler minimizes noise. The early phase (before vascular compensation) has the richest signal lode. PMID- 22095640 TI - The cox-maze procedure for lone atrial fibrillation: a single-center experience over 2 decades. AB - BACKGROUND: The Cox-Maze procedure (CMP) has achieved high success rates in the therapy of atrial fibrillation (AF) while becoming progressively less invasive. This report evaluates our experience with the CMP in the treatment of lone AF over 2 decades and compares the original cut-and-sew CMP-III to the ablation assisted CMP-IV, which uses bipolar radiofrequency and cryoenergy to create the original lesion pattern. METHODS AND RESULTS: Data were collected prospectively on 212 consecutive patients (mean age, 53.5+/-10.4 years; 78% male) who underwent a stand-alone CMP from 1992 through 2010. The median duration of preoperative AF was 6 (interquartile range, 2.9-11.5) years, with 48% paroxysmal and 52% persistent or long-standing persistent AF. Univariate analysis with preoperative and perioperative variables used as covariates for the CMP-III (n=112) and the CMP-IV (n=100) was performed. Overall, 30-day mortality was 1.4%, with no intraoperative deaths. Freedom from AF was 93%, and freedom from AF off antiarrhythmics was 82%, at a mean follow-up time of 3.6+/-3.1 years. Freedom from symptomatic AF at 10 years was 85%. Only 1 late stroke occurred, with 80% of patients not receiving anticoagulation therapy. The less invasive CMP-IV had significantly shorter cross-clamp times (41+/-13 versus 92+/-26 minutes; P<0.001) while achieving high success rates, with 90% freedom from AF and 84% freedom from AF off antiarrhythmics at 2 years. CONCLUSIONS: The CMP, although simplified and shortened by alternative energy sources, has excellent results, even with improved follow-up and stricter definition of failure. PMID- 22095641 TI - Association of SNPs linked to increased expression of SLC1A1 with schizophrenia. AB - Glutamate is one of the key molecules involved in signal transduction in the brain, and dysfunction of glutamate signaling could be linked to schizophrenia. The SLC1A1 gene located at 9p24 encodes the glutamate transporter EAAT3/EAAC1. To investigate the association between the SLC1A1 gene and schizophrenia in the Japanese population, we genotyped 19 tagging single nucleotide polymorphisms (tagSNPs) in the SLC1A1 gene in 576 unrelated individuals with schizophrenia and 576 control subjects followed by replication in an independent case-control study of 1,344 individuals with schizophrenia and 1,344 control subjects. In addition, we determined the boundaries of the copy number variation (CNV) region in the first intron (Database of Genomic Variants, chr9:4516796-4520549) and directly genotyped the CNV because of significant deviation from the Hardy-Weinberg equilibrium. The CNV was not associated with schizophrenia. Four SNPs showed a possible association with schizophrenia in the screening subjects and the associations were replicated in the same direction (nominal allelic P < 0.05), and, among them, an association with rs7022369 was replicated even after Bonferroni correction (allelic nominal P = 5 * 10(-5) , allelic corrected P = 2.5 * 10(-4) , allelic odds ratio, 1.30; 95% CI: 1.14-1.47 in the combined subjects). Expression analysis quantified by the real-time quantitative polymerase chain reaction in the postmortem prefrontal cortex of 43 Japanese individuals with schizophrenia and 11 Japanese control subjects revealed increased SLC1A1 expression levels in individuals homozygous for the rs7022369 risk allele (P = 0.003). Our findings suggest the involvement of SLC1A1 in the pathogenesis of schizophrenia. PMID- 22095642 TI - Assembling nanostructures for effective catalysis: supported palladium nanoparticle multicores coated by a hollow and nanoporous zirconia shell. AB - We report the synthesis and catalytic activities of highly stable, hollow nanoreactors, called SiO(2)/Pd/h-ZrO(2), which consist of silica microsphere (SiO(2))-supported Pd nanoparticle multicores (Pd) that are encapsulated with a hollow and nanoporous ZrO(2) shell (h-ZrO(2)). The SiO(2)/Pd/h-ZrO(2) nanoreactors are fabricated by first synthesizing SiO(2)/Pd/SiO(2)/ZrO(2) microspheres, and then etching the inner SiO(2) shell with dilute NaOH solution. The hollow and nanoporous ZrO(2) shell of the nanoreactors serves two important functions: 1) it provides reactants direct access to the Pd nanoparticle multicores inside the SiO(2)/Pd/h-ZrO(2) nanoreactors during catalysis, and 2) it stabilizes the Pd nanoparticles or protects them from aggregation/sintering. The fabrication of such structures capable of protecting the Pd nanoparticles from aggregation/sintering is of particular interest considering the fact that Pd nanoparticles generally have a high tendency to aggregate because of their high surface energies. Furthermore, the structures are interesting because the Pd nanoparticles are designed and synthesized here to have 'naked' surfaces or no organic surface-passivating ligands-that are often necessary to stabilize metallic nanoparticles-in order to increase their catalytic efficiency. The resulting SiO(2)/Pd/h-ZrO(2) nanoreactors show excellent catalytic activity, as shown in the hydrogenation of olefins and nitro groups, even at room temperature under moderate hydrogen pressure. This stems from the SiO(2)/Pd/h-ZrO(2) microspheres' high surface area and their small, stable, and bare Pd nanoparticles. Furthermore, the SiO(2)/Pd/h-ZrO(2) nanoreactor catalysts remain fairly stable after reaction and can be recycled multiple times without losing their high catalytic activities. PMID- 22095643 TI - Apigenin attenuates neointima formation via suppression of vascular smooth muscle cell phenotypic transformation. AB - Abnormal proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs) are critical factors in neointima formation during restenosis. The purpose of this study is to determine the efficacy and possible cell signaling mechanisms of apigenin in VSMC activation induced by platelet derived growth factor (PDGF)-BB and injury-induced neointima formation. Our data revealed a dose-dependent apigenin inhibition of PDGF-BB-induced proliferation of VSMCs by arresting cells in G0/G1-phase of the cell cycle as determined using 5 bromo-2'-deoxyuridine incorporation and flow cytometry. This was associated with the inhibition of cyclin-dependent kinase (CDK) 4,6 expression and an increase in p27Kip1 levels in PDGF-stimulated VSMCs. Moreover, apigenin was also found to regulate PDGF-induced migration and expression of smooth-muscle-specific contractile markers. Mechanistically, the PDGF-BB-induced phosphorylation of PDGF receptor beta (PDGF-Rbeta), Akt/glycogen synthase kinase(GSK)3beta, extracellular signal-regulated kinase1/2 (ERK1/2), and signal transducers and activators of transcription 3 (STAT3) is negatively modulated by apigenin. For the in vivo studies using a mouse carotid arterial injury model, the administration of apigenin resulted in a significant inhibition of the neointima/media ratio and proliferating cell nuclear antigen (PCNA)-positive cells. These results demonstrate that apigenin can suppress PDGF-induced VSMC activation and neointima hyperplasia after vascular injury; these beneficial effects are probably the result of the blockade of PDGF-Rbeta phosphorylation and its downstream signal transduction, including the Akt/GSK-3beta, ERK1/2, and STAT3 pathways. The results suggest that apigenin may be a potential therapeutic candidate for the prevention of restenosis. PMID- 22095644 TI - Anthrax toxin protective antigen--insights into molecular switching from prepore to pore. AB - The protective antigen is a key component of the anthrax toxin, as it allows entry of the enzymatic components edema factor and lethal factor into the host cell, through the formation of a membrane spanning pore. This event is absolutely critical for the pathogenesis of anthrax, and although we have yet to understand the mechanism of pore formation, recent developments have provided key insights into how this process may occur. Based on the available data, a model is proposed for the kinetic steps for protective antigen conversion from prepore to pore. In this model, the driving force for pore formation is the formation of the phi (phi)-clamp, a region that forms a leak-free seal around the translocating polypeptide. Formation of the phi-clamp elicits movements within the prepore that provide steric freedom for the subsequent conformational changes required to form the membrane spanning pore. PMID- 22095645 TI - High-throughput screening for inhibitors of sialyl- and fucosyltransferases. AB - Sweet screens: A high-throughput screening platform for identification of inhibitors of sialyl- and fucosyltransferases based on fluorescence polarization (FP) has been developed. An analogue of the natural donor substrate carrying a fluorescent label (green star) is transferred to a glycoprotein acceptor, which results in robust FP. The screening of 16,000 compounds against different glycosyltransferases has identified various interesting inhibitors. PMID- 22095646 TI - Remarkably selective recognition of iodobenzene derivatives by a macrocyclic bis Pt(II) metallohost. AB - We designed and synthesized self-assembled bis-Pt(II) dimer 1?4 BF(4) with quino[8,7-b][1,10]phenanthroline as an extended pi-face contact area, which acts as the first artificial receptor with high affinity toward iodinated aromatic compounds significantly based on noncovalent iodine???aromatic-plane interactions in a "side-on" fashion. Despite their structural similarity to a previously reported metallohost 2(4+) that bears 2,2':6',2''-terpyridine units, a dramatic change in selectivity toward substituted benzene derivatives was observed for 1(4+). (1)H NMR spectroscopic titration revealed a high affinity of 1(4+) towards haloarenes, with exceptionally large association constants for 2-iodophenol (K(a) = 16,000 M(-1)) and 1,2-diiodobenzene (K(a) = 21,000 M(-1)), which are 93- and 140-fold higher, respectively, than the values obtained for 2(4+). In addition, 1(4+) showed a remarkably high affinity and selectivity toward 2,6-diiodophenol (K(a) = 35,000 M(-1)), which is an important substructure of the thyroid hormone T(4). X-ray crystallography and theoretical calculations strongly suggest that "side-on" iodine???aromatic-plane interactions and pi-pi stacking contribute to the strong 1,2-diiodobenzene and 2,6-diiodophenol binding. The results obtained here give unique and valuable insight into the nature of halogen atom interactions in their "side-on" region with an electropositive aromatic plane, which may provide useful guidance for designing artificial receptors for iodinated biomolecules. PMID- 22095647 TI - A randomized and controlled study comparing immunoadsorption and plasma exchange in myasthenic crisis. AB - Myasthenic crisis is the most serious life-threatening event in Myasthenia gravis patients, affecting up to 27% within the first two years after onset of disease. Extracorporeal removal of circulating autoantibodies against the nicotinic acetylcholine receptor (AChRAb) by methods of therapeutic apheresis, e.g. plasma exchange (PE) and immunoadsorption (IA) had been demonstrated as effective treatment especially in acute situations of myasthenic crisis. However, controlled data comparing clinical safety and efficacy of both methods in a clinical study were not available. Here the results of a prospective randomized controlled clinical trial are presented, investigating 19 patients with myasthenic crisis, who were randomized to receive either PE (n = 10) or IA (n = 9) in addition to combined drug treatment. Patients received 3 to 5 (mean 3.5 for PE, and 3.4 for IA) treatments over a period of 7 days with a predefined treatment volume of 1.5 l plasma (i.e., 20-25 ml/kg plasma representing 0.5-0.6 patients' plasma volumes). Clinical courses were monitored using disease specific clinical scores. After initiation of IA or PE the mean value of Myasthenia scores decreased equally until Day 14 of the post-treatment phase. Patients from both treatment groups improved to a stable clinical status of Oosterhuis Classes 1 and 2. Substantial reduction of AChRAb was documented after each session of PE or IA. In the treatment period 16 adverse effects (seven serious adverse events, SAE) in the PE and 10 (1 SAE) in the IA group were observed. In conclusion, IA proved to be equally effective compared with PE treatment in patients with myasthenic crisis. Three to five treatment sessions using low plasma volume dosage of 20-25 ml/kg were adequate to improve clinically relevant symptoms significantly in most patients. PMID- 22095649 TI - To feed or what to feed in cirrhosis? PMID- 22095648 TI - Ensemble modeling of protein disordered states: experimental restraint contributions and validation. AB - Disordered states of proteins include the biologically functional intrinsically disordered proteins and the unfolded states of normally folded proteins. In recent years, ensemble-modeling strategies using various experimental measurements as restraints have emerged as powerful means for structurally characterizing disordered states. However, these methods are still in their infancy compared with the structural determination of folded proteins. Here, we have addressed several issues important to ensemble modeling using our ENSEMBLE methodology. First, we assessed how calculating ensembles containing different numbers of conformers affects their structural properties. We find that larger ensembles have very similar properties to smaller ensembles fit to the same experimental restraints, thus allowing a considerable speed improvement in our calculations. In addition, we analyzed the contributions of different experimental restraints to the structural properties of calculated ensembles, enabling us to make recommendations about the experimental measurements that should be made for optimal ensemble modeling. The effects of different restraints, most significantly from chemical shifts, paramagnetic relaxation enhancements and small-angle X-ray scattering, but also from other data, underscore the importance of utilizing multiple sources of experimental data. Finally, we validate our ENSEMBLE methodology using both cross-validation and synthetic experimental restraints calculated from simulated ensembles. Our results suggest that secondary structure and molecular size distribution can generally be modeled very accurately, whereas the accuracy of calculated tertiary structure is dependent on the number of distance restraints used. PMID- 22095650 TI - Real-time gene delivery vector tracking in the endo-lysosomal pathway of live cells. AB - Using live-cell confocal microscopy and particle tracking technology, the simultaneous transport of intracellular vesicles of the endo-lysosomal pathway and nonviral polyethylenimine (PEI)/DNA nanocomplexes was investigated. Due to potential problems associated with the use of acid-sensitive probes in combination with a gene vector that is hypothesized to buffer the pH of intracellular vesicles, the biological location of PEI/DNA gene vectors was revealed by probing their trafficking in cells expressing fluorescent versions of either early endosome antigen 1, a protein that localizes to early endosomes, or Niemann Pick C1, a protein that localizes to late endosomes and lysosomes. Studies directly show that PEI/DNA nanoparticles are actively transported within both early and late endosomes, and display similar overall transport rates in each. Additionally, gene vector transfer between endosomes is observed. Over time post-transfection, gene vectors accumulate in late endosomes/lysosomes; however, real-time escape of vectors from membrane-bound vesicles is not observed. PMID- 22095651 TI - Zeranol: doping offence or mycotoxin? A case-related study. AB - Zeranol ((7R,11S)-7,15,17-trihydroxy-11-methyl-12-oxabicyclo[12.4.0]octadeca 1(14),15,17-trien-13-one, also referred to as 7alpha-zearalanol, Ralone(r), Frideron(r), Ralgro(r), etc.) is a semi-synthetic estrogenic veterinary drug with growth-promoting properties. Its use regarding animal husbandry has been prohibited in the European Union since 1981 and, due to its anabolic effects, it is further recognized as a banned substance in sport. Numerous studies were conducted concerning the identification of the illicit application of zeranol to domestic livestock. These studies also considered the natural occurrence of zeranol as a metabolite of the mycotoxin zearalenone and the issue of differentiating both scenarios, i.e. illegal use or unintended contamination. Human sports drug testing authorities are facing comparable challenges since the deliberate misuse of the (for human application non-approved) drug should be discriminated from adverse analytical findings resulting from the biotransformation of the mycotoxin zearalenone possibly ingested with contaminated food. The active drug (zeranol), its major human metabolites (zearalanone, 7beta-zearalanol) and the mycotoxin (zearalenone) plus its major and unique metabolic products (alpha-zearalenol, beta-zearalenol) have been monitored in routine doping controls by means of validated gas chromatography (tandem) mass spectrometry (GC-(MS/)MS) methods since 1996, and between 2005 and 2010 four samples providing suspicious signals were detected. In agreement with literature data, in vitro metabolism studies demonstrated the metabolic pathway from zearalenone towards zeranol (and common metabolites). In contrast, an administration study urine sample (collected after oral application of 20 mg of zeranol) yielded only ultra-trace amounts of zearalenone and its characteristic metabolites, which supported the assumption that a mycotoxin contamination caused the finding of zeranol in the doping control specimens rather than a misuse of the anabolic agent. PMID- 22095652 TI - High resolution three-dimensional cine phase contrast MRI of small intracranial aneurysms using a stack of stars k-space trajectory. AB - PURPOSE: To develop a method for targeted volumetric, three directional cine phase contrast (PC) imaging with high spatial resolution in clinically feasible scan times. MATERIALS AND METHODS: A hybrid radial-Cartesian k-space trajectory is used for cardiac gated, volumetric imaging with three directional velocity encoding. Imaging times are reduced by radial undersampling and temporal viewsharing. Phase contrast angiograms are displayed in a new approach that addresses the concern of signal drop out in regions of slow flow. The feasibility of the PC stack of stars (SOS) trajectory was demonstrated with an in vivo study capturing 14 small intracranial aneurysms (2-10 mm). Aneurysm measures from six aneurysms also imaged with digital subtraction angiography (DSA) were compared with linear regression with those from the PC SOS images. RESULTS: All aneurysms were identified on the phase contrast angiograms. The geometric measures from PC SOS and DSA were in good agreement (linear regression: slope = 0.89, intercept = 0.35, R?2 = 0.88). CONCLUSION: PC SOS is a promising method for obtaining volumetric angiograms and cine phase contrast velocity measurements in three dimensions. Acquired spatial resolutions of 0.4 * 0.4 * (0.7-1.0) mm make this method especially promising for studying flow in small intracranial aneurysms. PMID- 22095653 TI - Lack of association between p.Ser167Asn variant of Parkin and Parkinson's disease: a meta-analysis of 15 studies involving 2,280 cases and 2,459 controls. AB - Previous clinical trials have evaluated the association between Parkin p.Ser167Asn (c.601G>A) variant and Parkinson's disease (PD) risk. However, the results remain conflicting rather than conclusive. Therefore, we performed this meta-analysis to assess whether pooled results show the association. We performed structured literature searches for studies addressing the association between the Parkin p.Ser167Asn variant and PD risk. We conducted analyses of study characteristics, heterogeneity, and funnel plot asymmetry in analyses analogous to additive, dominant, recessive, and general genetic models with the odds ratio (OR) as the measure of association. When 15 eligible studies (n = 4,739 subjects) were pooled into the meta-analysis, there was no evidence for significant association in additive genetic model between Parkin p. Ser167Asn variant and PD risk (OR = 1.02, 95% confidence interval (CI) = 0.83-1.25; P = 0.866). The OR for the dominant model was 1.06 (95% CI = 0.80-1.41) while the OR for the recessive model was 0.90 (95% CI = 0.71-1.14). The OR for the heterozygous was 1.07 (95% CI = 0.80-1.43) while the OR for the homozygotes was 1.19 (95% CI = 0.81-1.74). In the subgroup analysis by ethnicity, no significant association was found in any genetic model. Begg's funnel plot and Egger's test provided visual and statistical evidences for funnel plot symmetry, suggesting no presence of publication bias. In summary, the meta-analysis strongly suggests that Parkin p. Ser167Asn variant is not associated with PD risk. PMID- 22095654 TI - Overtures to takotsubo's cardiomyopathy. PMID- 22095655 TI - American Society for Preventive Cardiology Annual Debate: coronary heart disease in men and women--does one size fit all? PMID- 22095656 TI - Primary prevention of coronary heart disease in men and women: does 1 size fit all? Yes! AB - Cardiovascular disease remains the leading cause of mortality in both women and men in the industrialized nations. Coronary heart disease (CHD) accounts for the single largest share of this toll in both sexes. Although it had long been known that the number 1 cause of death in men is CHD, it was determined only relatively recently that this was also true in women. Identification of the traditional risk factors (RFs) for CHD by the Framingham Heart Study and other investigations during the last 5 decades has provided the basis of preventive cardiology. These RFs can be considered as fixed or modifiable. Numerous epidemiologic and clinical studies have demonstrated that, with few exceptions, the major RFs that increase the hazard for CHD are the same for both men and women, whether fixed (age, sex, family history) or modified (lipids, blood pressure, smoking). A number of other RFs are under investigation and await confirmation in rigorous prospective studies. Even those conditions unique to women, which can predispose patients to CHD, such as polycystic ovaries and complications of pregnancy, act through provocation of the traditional RFs. Thus, the large body of evidence that supports the similarity of RFs for CHD in men and women provides a rational foundation for similar strategies of prevention in the 2 sexes. PMID- 22095657 TI - Coronary heart disease in men and women: does 1 size fit all? No! PMID- 22095658 TI - Mortality trends for non-ST-segment elevation myocardial infarction (NSTEMI) in the United States from 1988 to 2004. AB - BACKGROUND: Non-ST-segment myocardial infarction (NSTEMI) is one of the major causes of hospital admissions. Mortality trend in patients with NSTEMI over the years has not been studied well. The goal of this study is to explore age adjusted long-term mortality trends from NSTEMI in the United States using a very large database. METHODS: We used the National Inpatient Sample (NIS) database, a component of the Health Care Cost and Utilization (HCUP) project, for this study. International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify NSTEMI cases in patients >40 years old. Age-adjusted mortality rates for NSTEMI cases were calculated by multiplying the age-specific mortality rates of NSTEMI by age-specific weights. RESULTS: A total of 1,400,234 patients above the age of 40 years were identified. The mean age of this cohort was 77.1+/-10.7 years, with a total of 179,361 deaths being reported over this 16-year period. Among patients who died, 51.2% were men and 48.8% were women. The age-adjusted mortality from NSTEMI declined from 1988 (727 per 100,000) to 2004 (305 per 100,000) until the middle of the decade when mortality from NSTEMI started leveling off. Total mortality decreased from 29.6% in 1988 to 11.3% in 2004. CONCLUSIONS: Our analysis showed a significant reduction in the age-adjusted and total mortality for NSTEMI over the years studied. The cause of this trend is not known but most likely reflects advancement in the treatment of patients with acute coronary syndrome. PMID- 22095659 TI - Clinical impact of off-label cardiac resynchronization therapy in end-stage heart failure patients on continuous intravenous inotrope. AB - BACKGROUND: Potential benefits of off-label cardiac resynchronization therapy (CRT) in end-stage heart failure (EHF) patients have not been fully investigated. HYPOTHESIS: Some EHF patients who are dependent on intravenous inotropes can benefit from CRT. METHODS: We retrospectively enrolled 14 EHF patients who were dependent on intravenous inotropes at the time of CRT implantation. Mean duration of inotropic support was 51 +/- 47 days before CRT device implantation. To identify the efficacy of CRT, we assessed the successful withdrawal rate from inotropic support and survival estimates after device implantation. We also tried to identify possible predictors for withdrawal by comparing patient demographics between successful withdrawal (SW) and nonwithdrawal (NW) groups. RESULTS: Successful withdrawal was achieved in 9 (64%) of 14 patients 46 +/- 33 days after CRT device implantation. Event-free survival was longer in the SW group than in the NW group (810 +/- 169 days vs 114 +/- 34 days; P = 0.007). In addition, patients in the SW group showed a higher previous surgery rate (89% vs 20%; P = 0.010) and a lower grade of mitral regurgitation (median, 0 vs 2; P = 0.010) than those in the NW group. CONCLUSIONS: Our retrospective data showed potential benefits of CRT among EHFpatients. Treatment of mitral regurgitation might be an essential qualification for managing EHF patients with CRT. PMID- 22095661 TI - Effect of reconstituted discoidal high-density lipoproteins on lipid mobilization in RAW 264.7 and CHOK1 cells. AB - Reconstituted discoidal high-density lipoproteins (rHDL) resemble nascent HDL, which are formed at the early reverse cholesterol transport steps, and constitute the initial cholesterol (Chol) acceptors from cell membranes. We have used different sized rHDL containing or not Chol, to test their abilities to promote cholesterol and phospholipid efflux from two different cell lines: Raw 264.7 macrophages and CHOK1 cells. All rHDL and lipid-free apolipoprotein A-I (apoA-I) were found to be bound to CHO and RAW cells. In RAW cells, a positive correlation between cellular binding and Chol removal was found for 78 and 96 A rHDL. Chol free rHDL were more effective than Chol-containing ones in binding to RAW cells and promoting Chol removal. These results were more evident in the 96 A rHDL. On the other hand, rHDL binding to CHO cells was relatively independent of disc size and Chol content. In spite of the fact that apoA-I and rHDL promoted Chol efflux from both cellular lines, only in CHOK1 cells this result was also associated to decrease Chol esterification. Among choline-containing phospholipids, only phosphatidylcholine (PC) (but not sphingomyelin) was detected to be effuxed from both cellular lines. With the only exception of Chol-free 96 A discs, the other rHDL as well as apoA-I promoted PC efflux from RAW cells. Chol-containing rHDL were more active than Chol-free ones of comparable size to promote PC efflux from RAW macrophages. Regarding CHO cells, only apoA-I and Chol-free 78 A rHDL were active enough to remove PC. PMID- 22095660 TI - Hepatocyte growth factor/c-met signaling is required for stem-cell-mediated liver regeneration in mice. AB - Hepatocyte growth factor (HGF)/c-Met supports a pleiotrophic signal transduction pathway that controls stem cell homeostasis. Here, we directly addressed the role of c-Met in stem-cell-mediated liver regeneration by utilizing mice harboring c met floxed alleles and Alb-Cre or Mx1-Cre transgenes. To activate oval cells, the hepatic stem cell (HSC) progeny, we used a model of liver injury induced by diet containing the porphyrinogenic agent, 3,5-diethocarbonyl-1,4-dihydrocollidine (DDC). Deletion of c-met in oval cells was confirmed in both models by polymerase chain reaction analysis of fluorescence-activated cell-sorted epithelial cell adhesion molecule (EpCam)-positive cells. Loss of c-Met receptor decreased the sphere-forming capacity of oval cells in vitro as well as reduced oval cell pool, impaired migration, and decreased hepatocytic differentiation in vivo, as demonstrated by double immunofluorescence using oval- (A6 and EpCam) and hepatocyte-specific (i.e. hepatocyte nuclear factor 4-alpha) antibodies. Furthermore, lack of c-Met had a profound effect on tissue remodeling and overall composition of HSC niche, which was associated with greatly reduced matrix metalloproteinase (MMP)9 activity and decreased expression of stromal-cell derived factor 1. Using a combination of double immunofluorescence of cell-type specific markers with MMP9 and gelatin zymography on the isolated cell populations, we identified macrophages as a major source of MMP9 in DDC-treated livers. The Mx1-Cre-driven c-met deletion caused the greatest phenotypic impact on HSCs response, as compared to the selective inactivation in the epithelial cell lineages achieved in c-Met(fl/fl); Alb-Cre(+/-) mice. However, in both models, genetic loss of c-met triggered a similar cascade of events, leading to the failure of HSC mobilization and death of the mice. CONCLUSION: These results establish a direct contribution of c-Met in the regulation of HSC response and support a unique role for HGF/c-Met as an essential growth-factor-signaling pathway for regeneration of diseased liver. PMID- 22095662 TI - The astrocytic lineage marker calmodulin-regulated spectrin-associated protein 1 (Camsap1): phenotypic heterogeneity of newly born Camsap1-expressing cells in injured mouse brain. AB - Calmodulin-regulated spectrin-associated protein 1 (Camsap1) has been recognized as a new marker for astrocytic lineage cells and is expressed on mature astrocytes in the adult brain (Yamamoto et al. [2009] J. Neurosci. Res. 87:503 513). In the present study, we found that newly born Camsap1-expressing cells exhibited regional heterogeneity in an early phase after stab injury of the mouse brain. In the surrounding area of the lesion site, Camsap1 was expressed on quiescent astrocytes. At 3 days after injury, Camsap1 immunoreactivity was upregulated on glial fibrillary acidic protein-immunoreactive (GFAP-ir) astrocytes. Some of these astrocytes incorporated bromodeoxyuridine (BrdU) together with re-expression of the embryonic cytoskeleton protein nestin. In the neighboring region of the lesion cavity, Camsap1 was expressed on GFAP-negative cells. At 3 days after injury, GFAP-ir astrocytes were absent around the lesion cavity. At this stage, NG2-ir cells immunopositive for Camsap1 and immunonegative for GFAP were distributed in border of the lesion cavity. By 10 days, Camsap1 immunoreactivity was exclusively detected on GFAP-ir reactive astrocytes devoid of NG2 immunoreactivity. BrdU pulse-chase labeling assay suggested the differentiation of Camsap1+/NG2+ cells into Camsap1+/GFAP+ astrocytes. In the subependymal zone of the lateral ventricle, Camsap1-ir cells increased after injury. Camsap1 immunoreactivity was distributed on ependymal and subependymal cells bearing various astrocyte markers, and BrdU incorporation was enhanced on such Camsap1-ir cells after injury. These results suggest that newly born reactive astrocytes are derived from heterogeneous Camsap1-expressing cells in the injured brain. PMID- 22095663 TI - Exploitation of a novel polysaccharide nanogel cross-linking membrane for guided bone regeneration (GBR). AB - Cholesterol-bearing pullulan (CHP) nanogel is a synthetic degradable biomaterial for drug delivery with high biocompatibility. Guided bone regeneration (GBR) is a bone augmentation technique in which a membrane is used to create and keep a secluded regenerative space. The purpose of the present study was to evaluate the effects of the novel CHP nanogel membrane in GBR. Thirty-six adult Wistar rats were used and bilaterally symmetrical full-thickness parietal bone defects of 5 mm diameter were created with a bone trephine burr. Each defect was covered with the collagen membrane or the CHP nanogel membrane or untreated without any membrane. The animals were sacrificed at 2, 4 and 8 weeks and analysed radiologically and histologically. Furthermore, after incubating human serum with CHP nanogel or collagen, the amount of PDGF in the serum was measured using ELISA. New bone formation in terms of bone volume was higher in the nanogel group than in the control or collagen groups at 2 and 4 weeks. At 8 weeks, both membrane groups showed higher bone volumes than the control group. Notably, the newly-formed bone in the bone defect in the nanogel group was uniform and histologically indistinguishable from the original bone, whereas in the collagen group the new bone showed an irregular structure that was completely different from the original bone. After incubating with CHP nanogel, the amount of PDGF in the serum decreased significantly. CHP nanogel GBR membrane favourably stimulated bone regeneration, in which a unique characteristic of CHP nanogel, the storage of endogenous growth factors, was likely implicated. PMID- 22095664 TI - Bromomaleimide-linked bioconjugates are cleavable in mammalian cells. PMID- 22095665 TI - Anthraquinone as a redox label for DNA: synthesis, enzymatic incorporation, and electrochemistry of anthraquinone-modified nucleosides, nucleotides, and DNA. AB - Modified 2'-deoxynucleosides and deoxynucleoside triphosphates (dNTPs) bearing anthraquinone (AQ) attached through an acetylene or propargylcarbamoyl linker at the 5-position of pyrimidine (C) or at the 7-position of 7-deazaadenine were prepared by Sonogashira cross-coupling of halogenated dNTPs with 2 ethynylanthraquinone or 2-(2-propynylcarbamoyl)anthraquinone. Polymerase incorporations of the AQ-labeled dNTPs into DNA by primer extension with KOD XL polymerase have been successfully developed. The electrochemical properties of the AQ-labeled nucleosides, nucleotides, and DNA were studied by cyclic and square-wave voltammetry, which show a distinct reversible couple of peaks around 0.4 V that make the AQ a suitable redox label for DNA. PMID- 22095666 TI - Ribonuclease A suggests how proteins self-chaperone against amyloid fiber formation. AB - Genomic analyses have identified segments with high fiber-forming propensity in many proteins not known to form amyloid. Proteins are often protected from entering the amyloid state by molecular chaperones that permit them to fold in isolation from identical molecules; but, how do proteins self-chaperone their folding in the absence of chaperones? Here, we explore this question with the stable protein ribonuclease A (RNase A). We previously identified fiber-forming segments of amyloid-related proteins and demonstrated that insertion of these segments into the C-terminal hinge loop of nonfiber-forming RNase A can convert RNase A into the amyloid state through three-dimensional domain-swapping, where the inserted fiber-forming segments interact to create a steric zipper spine. In this study, we convert RNase A into amyloid-like fibers by increasing the loop length and hence conformational freedom of an endogenous fiber-forming segment, SSTSAASS, in the N-terminal hinge loop. This is accomplished by sandwiching SSTSAASS between inserted Gly residues. With these inserts, SSTSAASS is now able to form the steric zipper spine, allowing RNase A to form amyloid-like fibers. We show that these fibers contain RNase A molecules retaining their enzymatic activity and therefore native-like structure. Thus, RNase A appears to prevent fiber formation by limiting the conformational freedom of this fiber-forming segment from entering a steric zipper. Our observations suggest that proteins have evolved to self-chaperone by using similar protective mechanisms. PMID- 22095667 TI - Decreased expression of Beclin 1 correlates with a metastatic phenotypic feature and adverse prognosis of gastric carcinomas. AB - BACKGROUND AND OBJECTIVES: Beclin 1 plays a critical role in the regulation of autophagy, apoptosis, differentiation and the development and progression of cancer. The clinicopathological significance of Beclin 1 expression in patients with gastric carcinoma (GC) has not been yet elucidated. METHODS: Immunohistochemistry (IHC) was performed to investigate the Beclin 1 expression in GCs and normal mucosal tissues. Receiver operating characteristic curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: The highly expressed Beclin 1 was observed in 90/155 (58.1%) of GCs, in 24/60 (40.0%) adjacent mucosal tissues and in 13/30 (43.3%) of normal gastric mucosa tissues (P = 0.036). Decreased expression of Beclin 1 in cancer cells was significantly correlated with poor differentiation, nodal and distant metastasis, advanced TNM stage, and tumor relapse. More importantly, Decreased expression of Beclin 1 was associated with shorter survival as evidenced by univariate and multivariate analysis. CONCLUSIONS: Our findings provide a basis for the concept that decreased expression of Beclin 1 in GC may be important in the acquisition of a metastatic phenotype, suggesting that decreased Beclin 1 expression, as examined by IHC, is an independent biomarker for poor prognosis of patients with GC. PMID- 22095668 TI - Measuring the quality of therapeutic apheresis care in the pediatric intensive care unit. AB - Our goal was to measure the quality of care provided in the Pediatric Intensive Care Unit (PICU) during Therapeutic Apheresis (TA). We described the care as a step by step process. We designed a flow chart to carefully document each step of the process. We then defined each step with a unique clinical indictor (CI) that represented the exact task we felt provided quality care. These CIs were studied and modified for 1 year. We measured our performance in this process by the number of times we accomplished the CI vs. the total number of CIs that were to be performed. The degree of compliance, with these clinical indicators, was analyzed and used as a metric for quality by calculating how close the process is running exactly as planned or "in control." The Apheresis Process was in control (compliance) for 47% of the indicators, as measured in the aggregate for the first observational year. We then applied the theory of Total Quality Management (TQM) through our Design, Measure, Analyze, Improve, and Control (DMAIC) model. We were able to improve the process and bring it into control by increasing the compliance to > 99.74%, in the aggregate, for the third and fourth quarter of the second year. We have implemented TQM to increase compliance, thus control, of a highly complex and multidisciplinary Pediatric Intensive Care therapy. We have shown a reproducible and scalable measure of quality for a complex clinical process in the PICU, without additional capital expenditure. PMID- 22095669 TI - Color tuning by local sputtering metal nanolayer on microstructured porous alumina. AB - This article reports a novel color tuning method by local sputtering nanolayers on microstructured porous alumina (PA) templates with different pore depths. With the aid of scanning electron microscopy observation, physical models of the original and sputtered PA templates are set up, and the details of the color tuning method are further proposed. Two series of colors covering the whole visible range are first obtained by respectively sputtering Cr and Ag nanolayers on two groups of PA templates with pore-depths ranging from 230 to 490 nm. A vivid colorful pattern of "Butterfly wings" is then prepared by local sputtering such Cr and Ag nanolayers on the surface of a PA with 310 nm pore-depth. The scanning electron microscopy images of Cr and Ag sputtered PA surfaces show different microstructures, which is in agreement with different color exhibiting. This method is expected to have a potential of being widely applied in the fields of micro-optics, microstructures, advanced materials, and micro/nanotechnology. PMID- 22095670 TI - Novel function of Niemann-Pick C1-like 1 as a negative regulator of Niemann-Pick C2 protein. AB - The hepatic expression of Niemann-Pick C1-like 1 (NPC1L1), which is a key molecule in intestinal cholesterol absorption, is high in humans. In addition to NPC1L1, Niemann-Pick C2 (NPC2), a secretory cholesterol-binding protein involved in intracellular cholesterol trafficking and the stimulation of biliary cholesterol secretion, is also expressed in the liver. In this study, we examined the molecular interaction and functional association between NPC1L1 and NPC2. In vitro studies with adenovirus-based or plasmid-mediated gene transfer systems revealed that NPC1L1 negatively regulated the protein expression and secretion of NPC2 without affecting the level of NPC2 messenger RNA. Experiments with small interfering RNA against NPC1L1 confirmed the endogenous association of these proteins. In addition, endocytosed NPC2 could compensate for the reduction of NPC2 in NPC1L1-overexpressing cells, and this demonstrated that the posttranscriptional regulation of NPC2 was dependent on a novel ability of NPC1L1 to inhibit the maturation of NPC2 and accelerate the degradation of NPC2 during its maturation. Furthermore, to confirm the physiological relevance of NPC1L1 mediated regulation, we analyzed human liver specimens and found a negative correlation between the protein levels of hepatic NPC1L1 and hepatic NPC2. CONCLUSION: NPC1L1 down-regulates the expression and secretion of NPC2 by inhibiting its maturation and accelerating its degradation. NPC2 functions as a regulator of intracellular cholesterol trafficking and biliary cholesterol secretion; therefore, in addition to its role in cholesterol re-uptake from the bile by hepatocytes, hepatic NPC1L1 may control cholesterol homeostasis via the down-regulation of NPC2. PMID- 22095671 TI - Multiple drugs and multiple targets: an analysis of the electrostatic determinants of binding between non-nucleoside HIV-1 reverse transcriptase inhibitors and variants of HIV-1 RT. AB - We present a systematic, computational analysis of the electrostatic component of binding of three HIV-1 RT inhibitors-nevirapine (NVP), efavirenz (EFV), and the recently approved rilpivirine (RPV)-to wild-type (WT) and mutant variants of RT. Electrostatic charge optimization was applied to determine how suited each molecule's charge distribution is for binding WT and individual mutants of HIV-1 RT. Although the charge distributions of NVP and EFV are rather far from being optimal for tight binding, RPVs charge distribution is close to the theoretical, optimal charge distribution for binding WT HIV-1 RT, although slight changes in charge can dramatically impact binding energetics. Moreover, toward the L100I/K103N double mutant, RPVs charge distribution is quite far from optimal. We also determine the contributions of chemical moieties on each molecule toward the electrostatic component of binding and show that different regions of a drug molecule may be used for recognition by different RT variants. The electrostatic contributions of certain RT residues toward drug binding are also computed to highlight critical residues for each interaction. Finally, the charge distribution of RPV is optimized to promiscuously bind to three RT variants rather than to each one in turn, with the resulting charge distribution being a compromise between the optimal charge distributions to each individual variant. Taken together, this work demonstrates that even in a binding site considered quite hydrophobic, electrostatics play a subtle yet varying role that must be considered in designing next-generation molecules that recognize rapidly mutating targets. PMID- 22095672 TI - Inversion-recovery-prepared dixon bSSFP: initial clinical experience with a novel pulse sequence for renal MRA within a breathhold. AB - PURPOSE: To evaluate the capability of a new breathhold non-contrast-enhanced MRA method (Non-contrast Outer Radial Inner Square k-space Scheme, NORISKS) to visualize renal arteries by comparing the method with a routine clinical but significantly longer non-contrast-enhanced (non-CE) MRA technique. MATERIALS AND METHODS: Eighteen subjects referred for abdominal MRI were examined with NORISKS and a routine non-contrast-enhanced MRA technique. Two versions of NORISKS were evaluated: with and without ECG gating. The images were then scored independently and in blinded manner by two radiologists on 5-point scales for visualization of the proximal and distal renal arteries and quality of fat suppression. RESULTS: No statistically significant difference was detected between NORISKS and routine clinical non-CE MRA in all categories except for visualization of the distal renal arteries where ungated NORISKS performed poorer than the routine non-CE MRA (P < 10(-4) ). CONCLUSION: We have demonstrated a promising non-CE MRA method for acquiring renal angiograms within a breathhold without any compromise in spatial resolution or coverage. ECG-gated NORISKS is able to acquire renal angiograms that are comparable to a routine clinical non-CE MRA method (Inhance IFIR, GE Healthcare), which requires approximately seven times the scan time of NORISKS. PMID- 22095673 TI - Proteomic analysis of berry-sizing effect of GA3 on seedless Vitis vinifera L. AB - Gibberellin (GA) is widely used in the table grape and raisin industries to enlarge the berries of seedless varieties. However, the mechanism underlying its berry-sizing effect is poorly understood. In this study, clusters of Centennial Seedless (Vitis vinifera L.) were treated with 30 ppm GA3 on day 12 after flowering, and berries were sampled at development stages I, II and III for proteomic analysis. Among the 1479 proteins detected on 2-DE maps, 19, 70 and 69 spots in stages I, II and III, respectively, showed an at least twofold difference in volume between treatments and controls. Of these, 125 proteins were successfully identified and assigned to eight functional groups, chief among them are metabolism and energy, stress response, expression regulation and cytoskeleton proteins. Stress-response proteins were predominantly down-regulated in GA3-treated berries in stages I and II, and significantly up-regulated in stage III. Up-regulation of cytoskeleton, cell-wall modification and other important proteins was found in the two latter stages of berry development. Our proteomic results and subsequent validation revealed, for the first time, the role of redox homeostasis in GA3-induced berry enlargement and markedly remodeled cellular protein expression in treated berries. PMID- 22095674 TI - Accuracy and sensitivity of residual DNA detection by QPCR is not predicted by target copy number. AB - A major issue in the use of mammalian cell culture in biopharmaceutical manufacturing is the removal of process related impurities, such as residual host cell DNA, during the product purification process. To ensure that sufficient DNA removal is achieved during purification, it is essential to have an accurate and sensitive assay for host cell DNA. The quantitative polymerase chain reaction (QPCR) is widely used for this purpose; however, the extent to which the choice of QPCR gene target can have an impact on final results requires further understanding. In the present study, we examined the relationship between the genomic copy number of eight different Chinese Hamster ovary (CHO) gene targets and the sensitivity and accuracy afforded by those targets in a residual host cell DNA QPCR assay. We also evaluated the use of each gene target for accurate measurement of residual DNA clearance using in-process purification samples from two CHO production cell lines. Our results revealed a correlation between gene target abundance and the potential sensitivity for use in a QPCR assay. However, we found that higher copy number gene targets do not provide the highest measurement or reveal the largest clearance of residual host cell DNA from purification samples. These findings suggest that different DNA sequences may clear or degrade at differential rates and highlight unexpected considerations that must be made in the choice of QPCR gene target when designing QPCR assays. PMID- 22095675 TI - Adoption of electronic health records by medical specialty societies. PMID- 22095676 TI - Are eating disorders a significant clinical issue in urban India? A survey among psychiatrists in Bangalore. AB - OBJECTIVE: It is believed that cultural changes such as urbanization and westernization can lead to increasing rates of eating disorders (EDs). A survey was conducted among psychiatrists in Bangalore, India to assess whether they were seeing more cases of ED in the last year. METHOD: Contact details of all psychiatrists in urban Bangalore were obtained from the directory of the local psychiatric society. These psychiatrists were contacted by telephone, email, or in person. A brief proforma was used to record information about the number and nature of eating disorders they had seen in their practice in the last one year. RESULTS: Sixty-six psychiatrists took part in the study. Thirty-eight (56%) were in private practice and 28 (42%) in teaching hospitals. 45 (67%), reported having seen patients with eating disorders in the last year. The total number of cases seen was 74. Of these, 32 were diagnosed as anorexia nervosa (AN), 12 as bulimia nervosa (BN), and 30 as eating disorders not otherwise specified (EDNOS). Sixteen (23.5%) respondents were of the opinion that EDs were increasing in Bangalore, 18 (26.5%) felt the rates were stable and 28 (42%) were not sure. DISCUSSION: Two thirds of psychiatrists reported seeing at least one case of ED indicating that EDs are not uncommon in urban India. Epidemiological studies of EDs in India are needed to provide better estimates of their prevalence. PMID- 22095677 TI - Advancing nasal reconstructive surgery: the application of tissue engineering technology. AB - Cartilage tissue engineering is a rapidly progressing area of regenerative medicine with advances in cell biology and scaffold engineering constantly being investigated. Many groups are now capable of making neocartilage constructs with some level of morphological, biochemical, and histological likeness to native human cartilage tissues. The application of this useful technology in articular cartilage repair is well described in the literature; however, few studies have evaluated its application in head and neck reconstruction. Although there are many studies on auricular cartilage tissue engineering, there are few studies regarding cartilage tissue engineering for complex nasal reconstruction. This study therefore highlighted the challenges involved with nasal reconstruction, with special focus on nasal cartilage tissue, and examined how advancements made in cartilage tissue engineering research could be applied to improve the clinical outcomes of total nasal reconstructive surgery. PMID- 22095679 TI - Regio- and stereoselective synthesis of cyclopentenones: intermolecular pseudo Pauson-Khand cyclization. PMID- 22095680 TI - Theoretical study of the photochemistry of a reversible three-state bis thiaxanthylidene molecular switch. AB - The ground- and the lowest singlet excited-state potential energy surfaces of the bis-thiaxanthylidene (3) molecular switch are investigated using a density functional method specifically designed to treat molecular systems typified by strong non-dynamic electron correlation. The results of the theoretical calculations suggest that the unique ability of substituted bis-thiaxanthylidenes to switch between three states of luminescence-non-fluorescent state, blue fluorescent state, and red fluorescent state-can be explained by specific features on the excited state potential energy surface: the potential barrier around the Franck-Condon point of the anti-folded conformer and the existence of conical intersection in the vicinity of the syn-folded conformer. It is suggested that the twisted conformer, if made more stable via chemical modification, should fluoresce in the near-infrared region (lambda~740-760 nm), thus offering a possibility for a four-state switching of luminescence in a single-component molecular system. PMID- 22095678 TI - Homeobox genes in obsessive-compulsive disorder. AB - BACKGROUND: Despite evidence that obsessive-compulsive disorder (OCD) is a familial neuropsychiatric condition, progress aimed at identifying genetic determinants of the disorder has been slow. The OCD Collaborative Genetics Study (OCGS) has identified several OCD susceptibility loci through linkage analysis. METHODS: In this study we investigate two regions on chromosomes 15q and 1q by first refining the linkage region using additional short tandem repeat polymorphic (STRP) markers. We then performed association analysis on single nucleotide polymorphisms (SNP) genotyped (markers placed every 2-4 kb) in the linkage regions in the OCGS sample of 376 rigorously phenotyped affected families. RESULTS: Three SNPs are most strongly associated with OCD: rs11854486 (P = 0.00005 [0.046 after adjustment for multiple tests]; genetic relative risk (GRR) = 11.1 homozygous and 1.6 heterozygous) and rs4625687 [P = 0.00007 (after adjustment = 0.06); GRR = 2.4] on 15q; and rs4387163 (P = 0.0002 (after adjustment = 0.08); GRR = 1.97) on 1q. The first SNP is adjacent to NANOGP8, the second SNP is in MEIS2, and the third is 150 kb between PBX1 and LMX1A. CONCLUSIONS: All the genes implicated by association signals are homeobox genes and are intimately involved in neurodevelopment. PBX1 and MEIS2 exert their effects by the formation of a heterodimeric complex, which is involved in development of the striatum, a brain region involved in the pathophysiology of OCD. NANOGP8 is a retrogene of NANOG, a homeobox transcription factor known to be involved in regulation of neuronal development. These findings need replication; but support the hypothesis that genes involved in striatal development are implicated in the pathogenesis of OCD. PMID- 22095681 TI - Colour evaluation of a phycobiliprotein-rich extract obtained from Nostoc PCC9205 in acidic solutions and yogurt. AB - BACKGROUND: Phycobiliproteins are coloured proteins produced by cyanobacteria, which have several applications because of their colour properties. However, there is no available information about the colour stability of phycobiliproteins from Nostoc sp. in food systems. The aim of this work was to study the colour stability of a purple-coloured phycobiliprotein-rich extract from the cyanobacterium Nostoc PCC9205 in acidic solutions and yogurt. RESULTS: Variations of pH for Nostoc PCC9205 extract have shown stability for the L* (lightness) and a* (redness) indexes in the range 1.0-7.0. The b* index (blueness), however, increased at pH values below 4.0, indicating loss of the blue colour. The Nostoc PCC9205 extract was used as colorant in yogurt (pH 4.17) stored for 60 days. Instrumental colour analysis showed no changes for the L* and a* indexes during storage, whereas the b* index changed after 20 days of storage. A multiple comparison test showed colour instability after 20 days of storage. A hedonic scale test performed on the 60th day of storage showed acceptability of the product. CONCLUSIONS: The red component of the phycobiliprotein-rich extract from Nostoc PCC9205 presented an improved stability in acidic media and yogurt compared with the blue component of this extract. PMID- 22095682 TI - Proper calibration of ultrasonic power enabled the quantitative analysis of the ultrasonication-induced amyloid formation process. AB - To elucidate the mechanisms of ultrasonication on the amyloid fibril formation, we quantitatively determined the ultrasonic power using both calorimetry and potassium iodide (KI) oxidation, and under the properly calibrated ultrasonic power, we investigated the ultasonication-induced amyloid formation process of the mouse prion protein (mPrP(23-231)). These methods revealed that the ultrasonic power in our system ranged from 0.3 to 2.7 W but entirely dependent on the positions of the ultrasonic stage. Intriguingly, the nucleation time of the amyloid fibrils was found to be shortened almost proportionally to the ultrasonic power, indicating that the probability of the occurrence of nucleus formation increases proportionally to the ultrasonic power. Moreover, mPrP(23-231) formed two types of aggregates: rigid fibrils and short fibrils with disordered aggregates, depending on the ultrasonic power. The nucleation of rigid fibrils required an ultrasonic power larger than 1.5 W. While at the strong ultrasonic power larger than 2.6 W, amyloid fibrils were formed early, but simultaneously fine fragmentation of fibrils occurred. Thus, an ultrasonic power of approximately 2.0 W would be suitable for the formation of rigid mPrP(23-231) fibrils under the conditions utilized (ultrasonication applied for 30 s every 9 min). As ultrasonication has been widely used to amplify the scrapie form of the prion protein, or other amyloids in vitro, the calorimetry and KI oxidation methods proposed here might help determining the adequate ultrasonic powers necessary to amplify them efficiently. PMID- 22095683 TI - Upregulation of recepteur d'origine nantais tyrosine kinase and cell invasiveness via early growth response-1 in gastric cancer cells. AB - Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in carcinogenesis of epithelial tumors. RON expression was induced by the tumor promoter, phorbol 12-myristate 13-acetate (PMA), in gastric adenocarcinoma AGS cells. Studies with deleted and site-directed mutagenesis of Egr-1 promoter and with expression vectors encoding Egr-1 confirmed that Egr-1 is essential for RON expression. In addition, AGS cells pretreated with PMA showed remarkably enhanced invasiveness, which was partially abrogated by siRNA-targeted RON and Egr-1. These results suggest that tumor promoter induces RON expression via Egr-1, which, in turn, stimulates cell invasiveness in AGS cells. PMID- 22095684 TI - Boceprevir. PMID- 22095685 TI - Temperature-dependent study reveals that dynamics of hydrophobic residues plays an important functional role in the mitochondrial Tim9-Tim10 complex. AB - Protein-protein interaction is a fundamental process in all major biological processes. The hexameric Tim9-Tim10 (translocase of inner membrane) complex of the mitochondrial intermembrane space plays an essential chaperone-like role during import of mitochondrial membrane proteins. However, little is known about the functional mechanism of the complex because the interaction is weak and transient. This study investigates how electrostatic and hydrophobic interactions affect the conformation and function of the complex at physiological temperatures, using both experimental and computational methods. The results suggest that, first, different complex conformational states exist at equilibrium, and the major difference between these states is the degree of hydrophobic interactions. Second, the conformational change mimics the biological activity of the complex as measured by substrate binding at the same temperatures. Finally, molecular dynamics simulation and detailed energy decomposition analysis provided supporting evidence at the atomic level for the presence of an excited state of the complex, the formation of which is largely driven by the disruption of hydrophobic interactions. Taken together, this study indicates that the dynamics of the hydrophobic residues plays an important role in regulating the function of the Tim9-Tim10 complex. PMID- 22095686 TI - Protein lipidation catalyzed by microbial transglutaminase. PMID- 22095687 TI - The A3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry, and in silico approaches. AB - Adenosine is an ubiquitous local modulator that regulates various physiological and pathological functions by stimulating four membrane receptors, namely A(1), A(2A), A(2B), and A(3). Among these G protein-coupled receptors, the A(3) subtype is found mainly in the lung, liver, heart, eyes, and brain in our body. It has been associated with cerebroprotection and cardioprotection, as well as modulation of cellular growth upon its selective activation. On the other hand, its inhibition by selective antagonists has been reported to be potentially useful in the treatment of pathological conditions including glaucoma, inflammatory diseases, and cancer. In this review, we focused on the pharmacology and the therapeutic implications of the human (h)A(3) adenosine receptor (AR), together with an overview on the progress of hA(3) AR agonists, antagonists, allosteric modulators, and radioligands, as well as on the recent advances pertaining to the computational approaches (e.g., quantitative structure-activity relationships, homology modeling, molecular docking, and molecular dynamics simulations) applied to the modeling of hA(3) AR and drug design. PMID- 22095688 TI - Transcriptional gene silencing of kallikrein 5 and kallikrein 7 using siRNA prevents epithelial cell detachment induced by alkaline shock in an in vitro model of eczema. AB - Eczema is widely considered to be an exacerbation of alkaline stress to the skin. Epidermal barrier dysfunction is a feature of eczema pathology, which predisposes affected individuals to distressing morbid symptoms. At least two serine proteases, stratum corneum chymotryptic enzyme (kallikrein 7 [KLK7]) and stratum corneum tryptic enzyme (kallikrien 5 [KLK5]), have increased activity levels in eczematous lesions and both have been implicated in the destruction of corneodesomosomes, which are crucial to epidermal integrity. The present in vitro study investigated whether transcriptional gene silencing after siRNA transfection could influence the activity of these signature enzymes in an in vitro model of eczema induced by alkaline shock. HaCaT epithelial cells were subjected to alkaline stress by the addition of 1,1,3,3-tetramethyl guanidine "superbase" (TMG) to the culture media. The culture media were subsequently tested for chymotryspin, trypsin, plasmin, and urokinase activity using colorimetric peptide assays and for reactive oxygen species using WST1 cell viability reagent. Cells that had been transfected with small interfering ribonucleic acid (siRNA) against KLK5 and KLK7 for 24 h before alkaline shock did not exhibit the increase in serine protease levels observed in untreated controls. Moreover, an endpoint MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) confirmed that detachment of cells from the culture substrate observed in alkaline-stressed cells did not occur in siRNA-treated cells. This in vitro study has established the proof-of-principle that siRNA therapy appears to mitigate the consequences of alkaline shock to the serine protease-associated fragility of epithelial cells that is characteristic of eczema. PMID- 22095689 TI - Display of functionally active PHB depolymerase on Escherichia coli cell surface. AB - The display of PHB depolymerase (PhaZ(RpiT1) ) from R. pickettii T1 on the surface of E. coli JM109 cells is realized using OprI of P. aeruginosa as the anchoring motif. The fusion protein is stably expressed and its surface localization is verified by immunofluorescence microscopy. The displayed PhaZ(RpiT1) retains its cleaving ability for soluble substrates as well as its ability to adsorb to the PHB surface, and also remains catalycically active in the degradation of insoluble polyester materials, in spite of the possible suppression of the enzyme movement on the polymer surface. The results demonstrate that PhaZ(RpiT1) -displaying E. coli shows potential for use as a whole-cell biocatalyst for the production of (R)-3-hydroxybutyrate monomers from insoluble PHB materials. PMID- 22095691 TI - C/EBPbeta and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2alpha as the inducer in chondrocytes. AB - To elucidate the molecular mechanism underlying the endochondral ossification process during the skeletal growth and osteoarthritis (OA) development, we examined the signal network around CCAAT/enhancer-binding protein-beta (C/EBPbeta, encoded by CEBPB), a potent regulator of this process. Computational predictions and a C/EBP motif-reporter assay identified RUNX2 as the most potent transcriptional partner of C/EBPbeta in chondrocytes. C/EBPbeta and RUNX2 were induced and co-localized in highly differentiated chondrocytes during the skeletal growth and OA development of mice and humans. The compound knockout of Cebpb and Runx2 in mice caused growth retardation and resistance to OA with decreases in cartilage degradation and matrix metalloproteinase-13 (Mmp-13) expression. C/EBPbeta and RUNX2 cooperatively enhanced promoter activity of MMP13 through specific binding to a C/EBP-binding motif and an osteoblast-specific cis acting element 2 motif as a protein complex. Human genetic studies failed to show the association of human CEBPB gene polymorphisms with knee OA, nor was there a genetic variation around the identified responsive region in the human MMP13 promoter. However, hypoxia-inducible factor-2alpha (HIF-2alpha), a functional and genetic regulator of knee OA through promoting endochondral ossification, was identified as a potent and functional inducer of C/EBPbeta expression in chondrocytes by the CEBPB promoter assay. Hence, C/EBPbeta and RUNX2, with MMP-13 as the target and HIF-2alpha as the inducer, control cartilage degradation. This molecular network in chondrocytes may represent a therapeutic target for OA. PMID- 22095690 TI - Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy. AB - X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal fatty acid transporter and subsequent accumulation of very-long-chain fatty acids (VLCFAs) are the common culprits to all forms of X-ALD, an aberrant microglial activation accounts for the cerebral forms, whereas inflammation allegedly plays no role in AMN. How VLCFA accumulation leads to neurodegeneration and what factors account for the dissimilar clinical outcomes and prognosis of X-ALD variants remain elusive. To gain insights into these questions, we undertook a transcriptomic approach followed by a functional-enrichment analysis in spinal cords of the animal model of AMN, the Abcd1(-) null mice, and in normal-appearing white matter of cAMN and cALD patients. We report that the mouse model shares with cAMN and cALD a common signature comprising dysregulation of oxidative phosphorylation, adipocytokine and insulin signaling pathways, and protein synthesis. Functional validation by quantitative polymerase chain reaction, western blots and assays in spinal cord organotypic cultures confirmed the interplay of these pathways through IkB kinase, being VLCFA in excess a causal, upstream trigger promoting the altered signature. We conclude that X-ALD is, in all its variants, a metabolic/inflammatory syndrome, which may offer new targets in X-ALD therapeutics. PMID- 22095693 TI - Rate of change in early Huntington's disease: a clinicometric analysis. AB - Sensitive outcome measures for patients with Huntington's disease (HD) are required for future clinical trials. Longitudinal data were collected from a 3 year study of 379 patients suffering from early HD who were not treated by antipsychotics. Progression of UHDRS item scores was evaluated by linear regression and slope, whereas correlation coefficient, standard error, and P values were estimated on the basis of the data of eight evaluations from screening to study end (36 months). For the functional assessment dimension, the proportion of "no" responses at baseline and at study end was determined. Linear progression was observed for the motor score and for all three functional measures (i.e., functional assessment score, independence assessment score, and total functional capacity score). In contrast, there was little evidence for progression of the behavioral assessment score over the study period, whereas the cognitive assessment score was intermediate. Twenty-two motor-score items showed linear progression, with a slope of >0.003. These included all chorea items, finger tapping and pronation/supination (left and right), gait, tongue protrusion, and tandem walking. Different symptom domains and individual items evolved at different rates in this group of patients suffering from early HD. It may be possible to select sensitive items to create a simplified version of the UHDRS, which would be more efficient and more sensitive for the assessment of disease progression in clinical trials and natural history studies. PMID- 22095692 TI - Pharmacologic activation of mitochondrial biogenesis exerts widespread beneficial effects in a transgenic mouse model of Huntington's disease. AB - There is substantial evidence that impairment of peroxisome proliferator activated receptor (PPAR)-gamma-coactivator 1alpha (PGC-1alpha) levels and activity play an important role in Huntington's disease (HD) pathogenesis. We tested whether pharmacologic treatment with the pan-PPAR agonist bezafibrate would correct a deficiency of PGC-1alpha and exert beneficial effects in a transgenic mouse model of HD. We found that administration of bezafibrate in the diet restored levels of PGC-1alpha, PPARs and downstream genes to levels which occur in wild-type mice. There were significant improvements in phenotype and survival. In the striatum, astrogliosis and neuronal atrophy were attenuated and numbers of mitochondria were increased. Bezafibrate treatment prevented conversion of type I oxidative to type II glycolytic muscle fibers and increased the numbers of muscle mitochondria. Finally, bezafibrate rescued lipid accumulation and apparent vacuolization of brown adipose tissue in the HD mice. These findings provide strong evidence that treatment with bezafibrate exerts neuroprotective effects which may be beneficial in the treatment of HD. PMID- 22095695 TI - Arterial spin labeling measurement of cerebral perfusion in children with sickle cell disease. AB - PURPOSE: To evaluate the applicability of arterial spin labeling (ASL) cerebral blood flow (CBF) measurements in children with sickle cell disease (SCD). MATERIALS AND METHODS: We included 12 patients and five controls. Conventional magnetic resonance imaging (MRI) (T2, fluid attenuated inversion recovery [FLAIR], and MR angiography) was performed to diagnose silent infarcts, vasculopathy, or leukoencephalopathy. Pseudo-continuous ASL was performed to measure CBF using two postlabeling delays to identify transit-time effects. Perfusion estimates were corrected for hematocrit and blood velocity in the labeling plane and compared to phase-contrast MR. CBF asymmetries between the flow maps of the left and right internal carotid arteries were tested for significance using paired t-tests. Significant asymmetries were expressed in terms of an asymmetry ratio (AR = absolute difference/mean). An AR >10% was considered clinically relevant. RESULTS: Mean CBF was higher in patients than in controls. Agreement between CBF and flow improved after applying hematocrit and velocity corrections. At a 2100 msec postlabeling delay one patient had a clinically relevant asymmetry. No association was observed between CBF asymmetries and silent infarcts. CONCLUSION: Care must be taken in the interpretation of ASL-CBF measurements in SCD patients. A long postlabeling delay with blood velocity correction anticipates overestimation of CBF asymmetries. PMID- 22095694 TI - Evidence for involvement of GNB1L in autism. AB - Structural variations in the chromosome 22q11.2 region mediated by nonallelic homologous recombination result in 22q11.2 deletion (del22q11.2) and 22q11.2 duplication (dup22q11.2) syndromes. The majority of del22q11.2 cases have facial and cardiac malformations, immunologic impairments, specific cognitive profile and increased risk for schizophrenia and autism spectrum disorders (ASDs). The phenotype of dup22q11.2 is frequently without physical features but includes the spectrum of neurocognitive abnormalities. Although there is substantial evidence that haploinsufficiency for TBX1 plays a role in the physical features of del22q11.2, it is not known which gene(s) in the critical 1.5 Mb region are responsible for the observed spectrum of behavioral phenotypes. We identified an individual with a balanced translocation 46,XY,t(1;22)(p36.1;q11.2) and a behavioral phenotype characterized by cognitive impairment, autism, and schizophrenia in the absence of congenital malformations. Using somatic cell hybrids and comparative genomic hybridization (CGH) we mapped the chromosome-22 breakpoint within intron 7 of the GNB1L gene. Copy number evaluations and direct DNA sequencing of GNB1L in 271 schizophrenia and 513 autism cases revealed dup22q11.2 in two families with autism and private GNB1L missense variants in conserved residues in three families (P = 0.036). The identified missense variants affect residues in the WD40 repeat domains and are predicted to have deleterious effects on the protein. Prior studies provided evidence that GNB1L may have a role in schizophrenia. Our findings support involvement of GNB1L in ASDs as well. PMID- 22095696 TI - Preparation and structural characterization of amorphous spray-dried dispersions of tenoxicam with enhanced dissolution. AB - Tenoxicam is a poorly soluble nonsteroidal anti-inflammatory drug. In this work, the solubility of tenoxicam is enhanced using amorphous spray-dried dispersions (SDDs) prepared using two molar equivalents of l-arginine and optionally with 10% 50% (w/w) polyvinylpyrrolidone (PVP). When added to the dispersions, PVP is shown to improve physical properties and also assists in maintaining supersaturation in solution. The dispersions provide a twofold increase over equilibrium solubility at the same pH. The dispersions are characterized using electron microscopy, vibrational spectroscopy, diffuse-reflectance visible spectroscopy, and X-ray powder diffraction. The structures of the dispersions are probed using solid state nuclear magnetic resonance (SSNMR) experiments applied to the (1) H, (13) C, and (15) N nuclei, including two-dimensional dipolar correlation experiments that detect molecular association and the formation of a glass solution between tenoxicam, l-arginine, and PVP. Other aspects of the amorphous structure, including hydrogen-bonding interactions and the ionization state of tenoxicam and l-arginine, are also explored using SSNMR methods. These methods are used to show that the SDDs contain an amorphous l-arginine salt of tenoxicam in a glass solution that also includes PVP when present. Finally, the dispersions show only a minor decrease in chemical stability during accelerated stability studies relative to a crystalline form of tenoxicam. PMID- 22095697 TI - A synthetic approach to a peptide alpha-thioester from an unprotected peptide through cleavage and activation of a specific peptide bond by N-acetylguanidine. PMID- 22095698 TI - Broadband dielectric spectroscopic, calorimetric, and FTIR-ATR investigations of D-arabinose aqueous solutions. AB - The dielectric relaxation behavior of D-arabinose aqueous solutions at different water concentrations is examined by broadband dielectric spectroscopy in the frequency range of 10(-2) -10(7) Hz and in the temperature range of 120-300 K. Differential scanning calorimetry is also performed to find the glass transition temperatures (T(g)). In addition, the same solutions are analyzed by Fourier transform infrared (FTIR) spectroscopy using the attenuated total reflectance (ATR) method at the same temperature interval and in the frequency range of 3800 2800 cm(-1). The temperature dependence of the relaxation times is examined for the different weight fractions (x(w)) of water along with the temperature dependence of dielectric strength. Two relaxation processes are observed in the aqueous solutions for all concentrations of water. The slower process, the so called primary relaxation process (process-I), is responsible for the T(g) whereas the faster one (designated as process-II) is due to the reorientational motion of the water molecules. As for other hydrophilic water solutions, dielectric data for process-II indicate the existence of a critical water concentration above which water mobility is less restricted. Accordingly, FTIR ATR measurements on aqueous solutions show an increment in the intensity (area) of the O-H stretching sub-band close to 3200 cm(-1) as the water concentration increases. PMID- 22095699 TI - Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells. AB - Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention. PMID- 22095700 TI - Extracellular matrix enhances differentiation of adipose stem cells from infrapatellar fat pad toward chondrogenesis. AB - The objective was to improve proliferation and chondrogenic potential of adipose stem cells (ASCs) by expansion on extracellular matrix (ECM) deposited by either ASCs or synovium-derived stem cells (SDSCs). ASCs isolated from porcine infrapatellar fat pad were separately expanded on conventional plastic flasks, ASC-deposited ECM and SDSC-deposited ECM. ASCs were centrifuged to form pellets and cultured in a serum-free chondrogenic medium with either TGFbeta3 or TGFbeta3 combined with BMP-6. Cell number yielded on ECM expansion did not show a significant difference in deposition between ASCs and SDSCs but was 6-10 times that grown on non-coated flasks. ECM-expanded ASCs exhibited a lower level of intracellular reactive oxygen species (ROS) compared to those grown on non-coated flasks. Typical chondrogenic markers, including type II collagen and glycosaminoglycans (GAGs), were intensively distributed in the pellets from ECM expanded ASCs instead of those from flask-grown cells. ASCs expanded on ECM, either from ASCs or SDSCs, exhibited a similar chondrogenic index (GAG:DNA), which was significantly higher than that from ASCs grown on non-coated flasks. The combination of TGFbeta3 and BMP-6 increased 36% more in ASC chondrogenic index than the treatment with TGFbeta3 alone. Interestingly, ECM pretreatment also decreased expanded ASC hypertrophic marker genes. ECM deposited by either ASCs or SDSCs did not exhibit enhanced adipogenic differentiation of ASCs. Our study indicates that the sequential application of ECM for cell expansion and combined TGFbeta3 with BMP-6 for chondrogenic differentiation may be a promising approach for ASC-based cartilage tissue engineering and regeneration. PMID- 22095701 TI - Effectiveness of cognitive-behavioural therapy plus pharmacotherapy in inpatient treatment of depressive disorders. AB - BACKGROUND: Meta-analyses show benefits for patients from a combination of medication and cognitive-behavioural psychotherapy. However, it is still unclear whether or not additional cognitive-behavioural therapy (CBT) also produces a better treatment outcome in a naturalistic psychiatric setting. METHODS: Two hundred six consecutively registered acute psychiatric inpatients with a unipolar depressive disorder were treated with additional CBT. This combined therapy was then compared with psychiatric primary care in an inpatient setting (clinical management). In addition to pharmacological treatment, 105 of the 206 patients also received symptom-focused CBT after hospitalization. Seventeen-item Hamilton Rating Scale for Depression (HAMD, primary outcome criterion), Beck Depression Inventory (BDI), Dysfunctional Attitude Scale, Clinical Global Impression Scale and the Global Assessment of Functioning were performed with all patients. RESULTS: Patients who were treated with additional CBT revealed a considerably greater reduction of depressive symptoms than in patients who received inpatient primary care only (HAMD: -22.21 versus -19.86, p = 0.027; BDI: 14.99 versus 11.36, p = 0.031). Moreover, remission rates were significantly higher (HAMD: 72% to 51%, p = 0.045; BDI: 58.8% versus 43.1%, p = 0.044) in the combined treatment group than in the primary care only group. LIMITATION: The naturalistic design and the inconsistent pharmacological treatment are design flaws. CONCLUSION: The results show that additional cognitive-behavioural treatment of depressive disorders notably improves outcome over standard procedure in acute psychiatric treatment. KEY PRACTITIONER MESSAGE: There is a need for treatment strategies to accompany medication. In the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D), only 33% of the patients reached remission criteria after the first antidepressant treatment step and only 50% after the second step. The strict inclusion criteria of randomized controlled trials often render their patient populations unrepresented. For an accurate view of treatment effectiveness, their results need to be complemented with results gained from trials in clinical practice. Additional cognitive-behavioural treatment notably improves treatment outcomes compared with standard treatments in the acute psychiatric treatment of depressive disorders. The results of this study under naturalistic conditions are an important addition to findings from randomized and controlled studies. PMID- 22095702 TI - Inward facing conformations of the MetNI methionine ABC transporter: Implications for the mechanism of transinhibition. AB - Two new crystal structures of the Escherichia coli high affinity methionine uptake ATP Binding Cassette (ABC) transporter MetNI, purified in the detergents cyclohexyl-pentyl-beta-D-maltoside (CY5) and n-decyl-beta-D-maltopyranoside (DM), have been solved in inward facing conformations to resolutions of 2.9 and 4.0 A, respectively. Compared to the previously reported 3.7 A resolution structure of MetNI purified in n-dodecyl-beta-D-maltopyranoside (DDM), the higher resolution of the CY5 data enabled significant improvements to the structural model in several regions, including corrections to the sequence registry, and identification of ADP in the nucleotide binding site. CY5 crystals soaked with selenomethionine established details of the methionine binding site in the C2 regulatory domain of the ABC subunit, including the displacement of the side chain of MetN residue methionine 301 by the exogenous ligand. When compared to the CY5 or DDM structures, the DM structure exhibits a significant repositioning of the dimeric C2 domains, including an unexpected register shift in the intermolecular beta-sheet hydrogen bonding between monomers, and a narrowing of the nucleotide binding space. The immediate proximity of the exogenous methionine binding site to the conformationally variable dimeric interface provides an indication of how methionine binding to the regulatory domains might mediate the phenomenon of transinhibition. PMID- 22095703 TI - Conformationally constrained sequence designs to bias monomer-dimer equilibriums in TASP systems. AB - We have designed template-assembled synthetic proteins (TASPs) with the intent of controlling their oligomeric state by stabilizing specific helical tertiary structures via histidine metal ion chelation or disulfide incorporation. In solution, cavitein Q4 was previously determined to interconvert between a four helix bundle monomer and an eight-helix bundle dimer. In this paper, we show that judicious mutation of cavitein Q4 can stabilize either the monomeric parallel four-helix bundle or the dimeric antiparallel eight-helix bundle structure. Cavitein Q4-E3H, designed to be dimeric, is indeed biased toward dimerization as a result of incorporation of histidines. Moreover, the addition of nickel was found to further increase the association constant of dimerization. Similarly, a cavitein designed to stabilize the monomeric structure via histidine metal ion chelation (Q4-H) was found to favor a monomer in solution upon addition of nickel. Lastly, a cavitein intended to stabilize a monomeric structure via disulfide incorporation (Q4-C2) is reported. Surprisingly, this disulfide cavitein yielded two products upon oxidation suggesting disulfide formation both above the cavitand template and below may be possible. Nevertheless, the two disulfide caviteins were shown to exist as monomers as per their design. PMID- 22095704 TI - alpha-Amylase inhibitors from an Indonesian medicinal herb, Phyllanthus urinaria. AB - BACKGROUND: Diabetes mellitus and associated diseases are an increasing problem around the world. One of the hyperglycemic remedies is glucose absorption reduction by suppressing carbohydrate digestion due to utilization of alpha amylase inhibitors. RESULTS: Prospective herbs were analyzed by in vitro enzyme assay to evaluate their inhibitory activity against porcine pancreatic amylase (PPA), and it was found that Phyllanthus urinaria and three other herbs to showed a potent inhibitory activity. A 50% aqueous methanol-soluble extract of the leaves of P. urinaria was chromatographed using a silica gel column. The active fractions were further purified by preparative high-performance liquid chromatography to isolate active principles against PPA. Structural determination revealed that these isolated compounds were gallic acid, corilagin, and macatannin B, and showed mild activity against PPA (activity in 1 mmol L-1 concentration: 23%, 21%, 33%, respectively). CONCLUSION: P. urinaria extracts show inhibitory activity against PPA. This activity, together with the information on isolated compounds, may benefit further exploration of P. urinaria utilization in the management of borderline diabetes patients. PMID- 22095705 TI - A magnetic resonance imaging study of 100 cases of arthroscopic acromioplasty. AB - BACKGROUND: A hooked-type acromion has been suspected to correlate with higher rotator cuff tear or impingement syndrome. However, correlation of acromial shape after acromioplasty with the rotator cuff retears and clinical results has not been studied before. PURPOSE: To assess the shape of the acromion after arthroscopic acromioplasty and to see if there is any relation with the rotator cuff retears and clinical results. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: One hundred consecutive patients who underwent acromioplasty using a posterior cutting block technique accompanied by rotator cuff repair were included in this study. The decision was made to perform acromioplasty intraoperatively after confirmation of external impingement. Postoperative acromial shape was evaluated according to whether the acromion was flat, curved, or hooked on coronal and sagittal planes on magnetic resonance imaging (MRI) at a mean 13.4 months after surgery. Retear rates and clinical scores were compared between the hooked acromion and the others on postoperative MRI. RESULTS: Preoperatively, only 29 patients had a hooked acromion on either coronal or sagittal plane MRI. After acromioplasty of those 100 patients, 23 still showed a hooked acromion. Twenty-six of 29 preoperatively hooked acromions were changed to nonhooked acromions, and 20 of 23 postoperatively hooked acromions had been nonhooked acromions preoperatively. No difference was found in the retear rate with respect to the postoperative acromial shape. Clinically, the American Shoulder and Elbow Surgeons (ASES) score was not different between the hooked acromion and the other group (82 vs 85, P = .099). However, the Constant score of the hooked acromion group was lower than that of the other group (74 vs 85, P = .036). Ninety-four of 100 patients were contacted again for the evaluation of the ASES score at a mean 36.5 months (range, 29-45 months) and showed no difference between the hooked acromion and the other group (87 vs 87, P = .903). CONCLUSION: Even with a standard posterior cutting block technique during acromioplasty, 23% of patients still showed a hooked acromion after arthroscopic acromioplasty. Using the signs of coracoacromial ligament impingement as an indication for acromioplasty might lead to hooked acromions postoperatively, which were nonhooked acromions preoperatively. However, the retear rate showed no difference according to the postoperative acromial shape. PMID- 22095707 TI - Should we change the priority for liver allocation for patients with the highest MELD score? PMID- 22095706 TI - Predictors of pain and function in patients with symptomatic, atraumatic full thickness rotator cuff tears: a time-zero analysis of a prospective patient cohort enrolled in a structured physical therapy program. AB - BACKGROUND: Although the prevalence of full-thickness rotator cuff tears increases with age, many patients are asymptomatic and may not require surgical repair. The factors associated with pain and loss of function in patients with rotator cuff tears are not well defined. PURPOSE: To determine which factors correlate with pain and loss of function in patients with symptomatic, atraumatic full-thickness rotator cuff tears who are enrolled in a structured physical therapy program. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A multicenter group enrolled patients with symptomatic, atraumatic rotator cuff tears in a prospective, nonrandomized cohort study evaluating the effects of a structured physical therapy program. Time-zero patient data were reviewed to test which factors correlated with Western Ontario Rotator Cuff (WORC) index and American Shoulder and Elbow Surgeons (ASES) scores. RESULTS: A total of 389 patients were enrolled. Mean ASES score was 53.9; mean WORC score was 46.9. The following variables were associated with higher WORC and ASES scores: female sex (P = .001), education level (higher education, higher score; P < .001), active abduction (degrees; P = .021), and strength in forward elevation (P = .002) and abduction (P = .007). The following variables were associated with lower WORC and ASES scores: male sex (P = .001), atrophy of the supraspinatus (P = .04) and infraspinatus (P = .003), and presence of scapulothoracic dyskinesia (P < .001). Tear size was not a significant predictor (WORC) unless comparing isolated supraspinatus tears to supraspinatus, infraspinatus, and subscapularis tears (P = .004). Age, tear retraction, duration of symptoms, and humeral head migration were not statistically significant. CONCLUSION: Nonsurgically modifiable factors, such as scapulothoracic dyskinesia, active abduction, and strength in forward elevation and abduction, were identified that could be addressed nonoperatively with therapy. Therefore, physical therapy for patients with symptomatic rotator cuff tears should target these modifiable factors associated with pain and loss of function. PMID- 22095708 TI - Assessing the degradation profile of functional aliphatic polyesters with precise control of the degradation products. AB - The pre-polymer poly(but-2-ene-1,4-diyl malonate) (PBM) and a series of PBM-based materials are shown to be degradable under physiological conditions in vitro and they are therefore presented as potential materials for biomedical applications. Four different PBM-based materials are synthesized: a PBM homopolymer, crosslinked PBM with and without spacer, and a triblock copolymer of PBM and PLLA with the PBM as an amorphous middle block. The polymers are subjected to hydrolytic degradation in phosphate-buffered saline at pH = 7.4 and 37 degrees C. The results show that all the PBM-based materials degrade without a rapid release of acidic degradation products or any substantial lowering of the pH that might jeopardize their biocompatibility. PMID- 22095709 TI - Mutation screening of the HDC gene in Chinese Han patients with Tourette syndrome. AB - Tourette Syndrome (TS) is a complex neuropsychiatric disorder characterized by vocal and motor tics. While environmental causes have been proposed to play a role, genetic factors are believed to be the main determinants of the disorder and its clinical manifestations. Recently, a heterozygous W317X mutation in the histidine decarboxylase gene (HDC) was reported to be responsible for TS in a two generation pedigree. To investigate whether the HDC gene play a role in TS in Chinese Han population, we performed genetic analysis of the coding region of the HDC gene in 100 Chinese Han patients with TS. Three variants were found including a C > T transition (IVS1 + 52C > T), a novel C > A transition (c.426C > A) in exon 4, and a novel G > A transition (c.1743G > A) in exon 12, both predicted with no amino acid change. Extended analysis was conducted in a total of 120 TS patients and 240 sex, age, and ethnicity matched healthy controls. No significant differences in genotypic and allele distribution between patients and controls for these three variants (P = 0.274, P = 1.000 and P = 0.632 for genotypic distribution, respectively; P = 0.143, P = 1.000 and P = 0.582 for allele distribution, respectively) were observed, suggesting variants in the HDC gene may play little or no role in TS susceptibility in Chinese Han population. PMID- 22095712 TI - The tumor suppressor ARF regulates innate immune responses in mice. AB - The innate immune system is the first line of defense against invading organisms, and TLRs are the main sensors of microbial components, initiating signaling pathways that induce the production of proinflammatory cytokines and type I IFNs. An antiviral action for the tumor suppressor alternative reading frame (ARF) has been reported; however, the precise role of ARF in innate immunity is unknown. In this study, we show that ARF plays an important role in regulation of inflammatory responses. In peritoneal macrophages and bone marrow-derived macrophages from ARF-deficient animals, the induction of proinflammatory cytokines and chemokines by TLR ligands was severely impaired. The altered responses of ARF(-/-) cells to TLR ligands result from aberrant activation of intracellular signaling molecules including MAPKs, IkappaBalpha degradation, and NF-kappaB activation. Additionally, animals lacking ARF were resistant to LPS induced endotoxic shock. This impaired activation of inflammation in ARF(-/-) mice was not restricted to TLRs, as it was also shown in response to non-TLR signaling pathways. Thus, ARF(-/-) mice were also unable to trigger a proper inflammatory response in experimental peritonitis or in 12-O-tetradecanoylphorbol 13-acetate-induced edema. Overexpression of ARF, but not its downstream target p53, rescued the ARF-deficient phenotype, increasing TLR4 levels and restoring inflammatory reaction. An increase in the E2F1 protein levels observed in ARF(-/ ) macrophages at basal condition and after LPS stimulation may be involved in the impaired response in this system, as E2F1 has been described as an inflammatory suppressor. These results indicate that tumor suppressor ARF is a new regulator of inflammatory cell signaling. PMID- 22095711 TI - Guanylate binding protein 4 negatively regulates virus-induced type I IFN and antiviral response by targeting IFN regulatory factor 7. AB - IRF7 is known as the master regulator in virus-triggered induction of type I IFNs (IFN-I). In this study, we identify GBP4 virus-induced protein interacting with IRF7 as a negative regulator for IFN-I response. Overexpression of GBP4 inhibits virus-triggered activation of IRF7-dependent signaling, but has no effect on NF kappaB signaling, whereas the knockdown of GBP4 has opposite effects. Furthermore, the supernatant from Sendai virus-infected cells in which GBP4 have been silenced inhibits the replication of vesicular stomatitis virus more efficiently. Competitive coimmunoprecipitation experiments indicate that overexpression of GBP4 disrupts the interactions between TRAF6 and IRF7, resulting in impaired TRAF6-mediated IRF7 ubiquitination. Our results suggest that GBP4 is a negative regulator of virus-triggered IFN-I production, and it is identified as a novel protein targeting IRF7 and inhibiting its function. PMID- 22095713 TI - Redox remodeling by dendritic cells protects antigen-specific T cells against oxidative stress. AB - Microorganisms and microbial products induce the release of reactive oxygen species (ROS) from monocytes and other myeloid cells, which may trigger dysfunction and apoptosis of adjacent lymphocytes. Therefore, T cell-mediated immunity is likely to comprise mechanisms of T cell protection against ROS inflicted toxicity. The present study aimed to clarify the dynamics of reduced sulfhydryl groups (thiols) in human T cells after presentation of viral and bacterial Ags by dendritic cells (DCs) or B cells. DCs, but not B cells, efficiently triggered intra- and extracellular thiol expression in T cells with corresponding Ag specificity. After interaction with DCs, the Ag-specific T cells acquired the capacity to neutralize exogenous oxygen radicals and resisted ROS induced apoptosis. Our results imply that DCs provide Ag-specific T cells with antioxidative thiols during Ag presentation, which suggests a novel aspect of DC/T cell cross-talk of relevance to the maintenance of specific immunity in inflamed or infected tissue. PMID- 22095710 TI - The proteoglycan biglycan enhances antigen-specific T cell activation potentially via MyD88 and TRIF pathways and triggers autoimmune perimyocarditis. AB - Biglycan is a proteoglycan ubiquitously present in extracellular matrix of a variety of organs, including heart, and it was reported to be overexpressed in myocardial infarction. Myocardial infarction may be complicated by perimyocarditis through unknown mechanisms. Our aim was to investigate the capacity of TLR2/TLR4 ligand biglycan to enhance the presentation of specific Ags released upon cardiomyocyte necrosis. In vitro, OVA-pulsed bone marrow-derived dendritic cells from wild-type (WT; C57BL/6) and TLR2-, TLR4-, MyD88-, or TRIF deficient mice were cotreated with LPS, biglycan, or vehicle and incubated with OVA-recognizing MHC I- or MHC II-restricted T cells. Biglycan enhanced OVA specific cross-priming by >80% to MHC I-restricted T cells in both TLR2- and TLR4 pathway-dependent manners. Accordingly, biglycan-induced cross-priming by both MyD88- and TRIF-deficient dendritic cells (DCs) was strongly diminished. OVA specific activation of MHC II-restricted T cells was predominantly TLR4 dependent. Our first in vivo correlate was a model of experimental autoimmune perimyocarditis triggered by injection of cardiac Ag-pulsed DCs (BALB/c). Biglycan-treated DCs triggered perimyocarditis to a comparable extent and intensity as LPS-treated DCs (mean scores 1.3 +/- 0.3 and 1.5 +/- 0.4, respectively). Substitution with TLR4-deficient DCs abolished this effect. In a second in vivo approach, WT and biglycan-deficient mice were followed 2 wk after induction of myocardial infarction. WT mice demonstrated significantly greater myocardial T lymphocyte infiltration in comparison with biglycan-deficient animals. We concluded that the TLR2/4 ligand biglycan, a component of the myocardial matrix, may enhance Ag-specific T cell priming, potentially via MyD88 and TRIF, and stimulate autoimmune perimyocarditis. PMID- 22095714 TI - Cathelicidin LL-37 increases lung epithelial cell stiffness, decreases transepithelial permeability, and prevents epithelial invasion by Pseudomonas aeruginosa. AB - In addition to its antibacterial activity, the cathelicidin-derived LL-37 peptide induces multiple immunomodulatory effects on host cells. Atomic force microscopy, F-actin staining with phalloidin, passage of FITC-conjugated dextran through a monolayer of lung epithelial cells, and assessment of bacterial outgrowth from cells subjected to Pseudomonas aeruginosa infection were used to determine LL 37's effect on epithelial cell mechanical properties, permeability, and bacteria uptake. A concentration-dependent increase in stiffness and F-actin content in the cortical region of A549 cells and primary human lung epithelial cells was observed after treatment with LL-37 (0.5-5 MUM), sphingosine 1-phosphate (1 MUM), or LPS (1 MUg/ml) or infection with PAO1 bacteria. Other cationic peptides, such as RK-31, KR-20, or WLBU2, and the antibacterial cationic steroid CSA-13 did not reproduce the effect of LL-37. A549 cell pretreatment with WRW4, an antagonist of the transmembrane formyl peptide receptor-like 1 protein attenuated LL-37's ability to increase cell stiffness. The LL-37-mediated increase in cell stiffness was accompanied by a decrease in permeability and P. aeruginosa uptake by a confluent monolayer of polarized normal human bronchial epithelial cells. These results suggested that the antibacterial effect of LL-37 involves an LL-37 dependent increase in cell stiffness that prevents epithelial invasion by bacteria. PMID- 22095715 TI - Stable coordination of the inhibitory Ca2+ ion at the metal ion-dependent adhesion site in integrin CD11b/CD18 by an antibody-derived ligand aspartate: implications for integrin regulation and structure-based drug design. AB - A central feature of integrin interaction with physiologic ligands is the monodentate binding of a ligand carboxylate to a Mg(2+) ion hexacoordinated at the metal ion-dependent adhesion site (MIDAS) in the integrin A domain. This interaction stabilizes the A domain in the high-affinity state, which is distinguished from the default low-affinity state by tertiary changes in the domain that culminate in cell adhesion. Small molecule ligand-mimetic integrin antagonists act as partial agonists, eliciting similar activating conformational changes in the A domain, which has contributed to paradoxical adhesion and increased patient mortality in large clinical trials. As with other ligand mimetic integrin antagonists, the function-blocking mAb 107 binds MIDAS of integrin CD11b/CD18 A domain (CD11bA), but in contrast, it favors the inhibitory Ca(2+) ion over the Mg(2+) ion at MIDAS. We determined the crystal structures of the Fab fragment of mAb 107 complexed to the low- and high-affinity states of CD11bA. Favored binding of the Ca(2+) ion at MIDAS is caused by the unusual symmetric bidentate ligation of a Fab-derived ligand Asp to a heptacoordinated MIDAS Ca(2+) ion. Binding of the Fab fragment of mAb 107 to CD11bA did not trigger the activating tertiary changes in the domain or in the full-length integrin. These data show that the denticity of the ligand Asp/Glu can modify the divalent cation selectivity at MIDAS and hence integrin function. Stabilizing the Ca(2+) ion at MIDAS by bidentate ligation to a ligand Asp/Glu may provide one approach for designing pure integrin antagonists. PMID- 22095716 TI - Induction of endoplasmic reticulum-endosome fusion for antigen cross-presentation induced by poly (gamma-glutamic acid) nanoparticles. AB - We previously reported that poly (gamma-glutamic acid)-based nanoparticles (gamma PGA NPs) are excellent vaccine carriers for inducing efficient cross-presentation in dendritic cells, thereby producing strong antitumor immunity in vivo. Analyzing the mechanism of cross-presentation induced by gamma-PGA NPs will be useful toward designing novel vaccine carriers. In this study, we show an intracellular mechanism of efficient cross-presentation induced by OVA-loaded gamma-PGA NPs. Cross-presentation induced by gamma-PGA NPs depended on cytoplasmic proteasomes and TAP, similar to the classical MHC class I presentation pathway for endogenous Ags. Intracellular behavior analyzed by confocal laser scanning microscopy revealed that encapsulated OVA and gamma-PGA accumulated in both the endoplasmic reticulum (ER) and endosome compartments within 2 h. At the same time, electron microscopy analysis clearly showed that intracellular gamma-PGA NPs and encapsulated Au NPs were enveloped in endosome like vesicles, not in the ER. These findings strongly suggest that gamma-PGA NPs enhance ER-endosome fusion for cross-presentation. Moreover, inhibition of ER translocon sec61 significantly decreased the gamma-PGA NP/OVA-mediated cross presentation efficiency, indicating that sec61 is important for transporting Ags from the fused ER-endosome to the cytoplasm. These findings imply that the ER endosome complex is key for the efficient cross-presentation of Ags encapsulated in gamma-PGA NPs. PMID- 22095717 TI - Micrometer-sized titanium particles can induce potent Th2-type responses through TLR4-independent pathways. AB - Wear debris in joint replacements has been suggested as a cause of associated tissue-damaging inflammation. In this study, we examined whether solid titanium microparticles (mTi) of sufficient size to accumulate as wear debris could stimulate innate or adaptive immunity in vivo. mTi, administered in conjunction with OVA, promoted total and Ag-specific elevations in serum IgE and IgG1. Analysis of transferred transgenic OVA-specific naive T cells further showed that mTi acted as an adjuvant to drive Ag-specific Th2 cell differentiation in vivo. Assessment of the innate response indicated that mTi induced rapid recruitment and differentiation of alternatively activated macrophages in vivo, through IL-4- and TLR4-independent pathways. These studies suggest that solid microparticles alone can act as adjuvants to induce potent innate and adaptive Th2-type immune responses and further suggest that wear debris in joint replacements may have Th2 type inflammatory properties. PMID- 22095720 TI - Simultaneous detection and analysis of protein aggregation and protein unfolding by size exclusion chromatography with post column addition of the fluorescent dye BisANS. AB - For development and optimization of protein formulation sensitive analytical tools are required to follow both aggregation and changes in protein structure. The latter can be seen as the beginning of physical instability leading to aggregation. The focus of this work laid on the development of a novel analysis simultaneously detecting changes in protein conformation and the formation of oligomers. By adding the extrinsic fluorescent dye 4,4'-dianilino-1,1'-binaphthyl 5,5'-disulfonic acid dipotassium salt (BisANS) after size exclusion chromatography (SEC) and UV detection, it was possible to separate protein monomer and oligomers by size, analyze the amount of formed oligomers quantitatively using UV detection, and observe changes in protein structure of different protein species by fluorescence detection. This enabled us to distinguish between native-like and denatured oligomers and monomers formed under different stress conditions. Correspondingly, increased fluorescence reflecting partial unfolding was assigned specifically to monomer, oligomer, or both. The unfolding of monomer is not traceable by commonly used detection methods, but its monitoring may provide important information about activity and long-term stability. By adding the dye after SEC and UV detection, interferences with prior detectors are precluded, excipients are separated avoiding interferences with the protein-dye interaction and, in addition, the dye-protein interaction cannot impact the aggregation formation, as added after the separation of monomer and aggregates. PMID- 22095719 TI - Comparison of alternative models for linking drug exposure with adverse effects. AB - Pharmacoepidemiology investigates associations between time-varying medication use/dose and risk of adverse events. Applied research typically relies on a priori chosen simple conventional models, such as current dose or any use in the past 3 months. However, different models imply different risk predictions, and only one model can be etiologically correct in any specific applications. We first formally defined several candidate models mapping the time vector of past drug doses (X (t), t = 1, ... ,u) into the value of a time-varying exposure metric M(u) at current time u. In addition to conventional one-parameter models, we considered two-parameter models accounting for recent dose increase or withdrawal and a flexible spline-based weighted cumulative exposure (WCE) model that defines M(u) as the weighted sum of past doses. In simulations, we generated event times assuming one of the models was correct and then analyzed the data with all candidate models. We demonstrated that the minimum AIC criterion is able to identify the correct model as the best-fitting model or one of the equivalent (within 4 AIC points of the minimum) models in a vast majority of simulated samples, especially with 500 or more events. We also showed how relying on an incorrect a priori chosen model may largely reduce the power to test for an association. Finally, we demonstrated how the flexible WCE estimates may help with model diagnostics even if the correct model is not WCE. We illustrated the practical advantages of AIC-based a posteriori model selection and WCE modeling in a real-life pharmacoepidemiology example. PMID- 22095718 TI - Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal beta-catenin pathway function in an Alzheimer's disease model. AB - Inflammation is a key pathological hallmark of Alzheimer's disease (AD), although its impact on disease progression and neurodegeneration remains an area of active investigation. Among numerous inflammatory cytokines associated with AD, IL-1beta in particular has been implicated in playing a pathogenic role. In this study, we sought to investigate whether inhibition of IL-1beta signaling provides disease modifying benefits in an AD mouse model and, if so, by what molecular mechanisms. We report that chronic dosing of 3xTg-AD mice with an IL-1R blocking Ab significantly alters brain inflammatory responses, alleviates cognitive deficits, markedly attenuates tau pathology, and partly reduces certain fibrillar and oligomeric forms of amyloid-beta. Alterations in inflammatory responses correspond to reduced NF-kappaB activity. Furthermore, inhibition of IL-1 signaling reduces the activity of several tau kinases in the brain, including cdk5/p25, GSK-3beta, and p38-MAPK, and also reduces phosphorylated tau levels. We also detected a reduction in the astrocyte-derived cytokine, S100B, and in the extent of neuronal Wnt/beta-catenin signaling in 3xTg-AD brains, and provided in vitro evidence that these changes may, in part, provide a mechanistic link between IL-1 signaling and GSK-3beta activation. Taken together, our results suggest that the IL-1 signaling cascade may be involved in one of the key disease mechanisms for AD. PMID- 22095721 TI - A collagen network phase improves cell seeding of open-pore structure scaffolds under perfusion. AB - Scaffolds with open-pore morphologies offer several advantages in cell-based tissue engineering, but their use is limited by a low cell-seeding efficiency. We hypothesized that inclusion of a collagen network as filling material within the open-pore architecture of polycaprolactone-tricalcium phosphate (PCL-TCP) scaffolds increases human bone marrow stromal cells (hBMSCs) seeding efficiency under perfusion and in vivo osteogenic capacity of the resulting constructs. PCL TCP scaffolds, rapid prototyped with a honeycomb-like architecture, were filled with a collagen gel and subsequently lyophilized, with or without final crosslinking. Collagen-free scaffolds were used as controls. The seeding efficiency was assessed after overnight perfusion of expanded hBMSCs directly through the scaffold pores using a bioreactor system. By seeding and culturing freshly harvested hBMSCs under perfusion for 3 weeks, the osteogenic capacity of generated constructs was tested by ectopic implantation in nude mice. The presence of the collagen network, independently of the crosslinking process, significantly increased the cell seeding efficiency (2.5-fold), and reduced the loss of clonogenic cells in the supernatant. Although no implant generated frank bone tissue, possibly due to the mineral distribution within the scaffold polymer phase, the presence of a non-crosslinked collagen phase led to in vivo formation of scattered structures of dense osteoids. Our findings verify that the inclusion of a collagen network within open morphology porous scaffolds improves cell retention under perfusion seeding. In the context of cell-based therapies, collagen-filled porous scaffolds are expected to yield superior cell utilization, and could be combined with perfusion-based bioreactor devices to streamline graft manufacture. PMID- 22095722 TI - Chiral iridium catalysts bearing spiro pyridine-aminophosphine ligands enable highly efficient asymmetric hydrogenation of beta-aryl beta-ketoesters. PMID- 22095724 TI - Fluid pressure induces osteoclast differentiation comparably to titanium particles but through a molecular pathway only partly involving TNFalpha. AB - In contrast to the well-understood inflammatory pathway driven by TNFalpha, by which implant-derived particles induce bone resorption, little is known about the process in which loosening is generated as a result of force-induced mechanical stimulus at the bone-implant interface. Specifically, there is no knowledge as to what cells or signaling pathways couple mechanical stimuli to bone resorption in context of loosening. We hypothesized that different stimuli, i.e., fluid flow versus wear particles, act through different cytokine networks for activation and localization of osteoclasts. By using an animal model in which osteoclasts and bone resorption were induced by fluid pressure or particles, we were able to detect distinct differences in osteoclast localization and inflammatory gene expression between fluid pressure and titanium particles. Fluid pressure recruits and activates osteoclasts with bone marrow contact away from the fluid pressure exposure zone, whereas titanium particles recruit and activate osteoclasts in areas in direct contact to particles. Fluid pressure induced weaker expression of the selected inflammatory related genes, although the eventual degree of osteoclast induction was similar in both models. Using TNFalphaRa (4 mg/kg) (Enbrel) and dexamethasone (2 mg/kg) as specific and more general suppressors of inflammation we showed that the TNFalphaRa failed to generate statistically impaired osteoclast generation while dexamethasone was much more potent. These results demonstrate that fluid pressure induces osteoclasts at a different localization than titanium particles by a molecular pathway less associated with TNFalpha and the innate system, which open up for other pathways controlling pressure induced osteoclastogenesis. PMID- 22095723 TI - Comparison of a 28-channel receive array coil and quadrature volume coil for morphologic imaging and T2 mapping of knee cartilage at 7T. AB - PURPOSE: To compare a new birdcage-transmit, 28-channel receive array (28-Ch) coil and a quadrature volume coil for 7T morphologic MRI and T2 mapping of knee cartilage. MATERIALS AND METHODS: The right knees of 10 healthy subjects were imaged on a 7T whole body magnetic resonance (MR) scanner using both coils. 3D fast low-angle shot (3D-FLASH) and multiecho spin-echo (MESE) sequences were implemented. Cartilage signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), thickness, and T2 values were assessed. RESULTS: SNR/CNR was 17%-400% greater for the 28-Ch compared to the quadrature coil (P <= 0.005). Bland-Altman plots show mean differences between measurements of tibial/femoral cartilage thickness and T2 values obtained with each coil to be small (-0.002 +/- 0.009 cm / 0.003 +/- 0.011 cm) and large (-6.8 +/- 6.7 msec/-8.2 +/- 9.7 msec), respectively. For the 28-Ch coil, when parallel imaging with acceleration factors (AF) 2, 3, and 4 was performed SNR retained was: 62%-69%, 51%-55%, and 39%-45%. CONCLUSION: A 28-Ch knee coil provides increased SNR/CNR for 7T cartilage morphologic imaging and T2 mapping. Coils should be switched with caution during clinical studies because T2 values may differ. The greater SNR of the 28-Ch coil could be used to perform parallel imaging with AF2 and obtain similar SNR as the quadrature coil. PMID- 22095725 TI - Revisiting the folding kinetics of bacteriorhodopsin. AB - The elucidation of the physical principles that govern the folding and stability of membrane proteins is one of the greatest challenges in protein science. Several insights into the folding of alpha-helical membrane proteins have come from the investigation of the conformational equilibrium of H. halobium bacteriorhodopsin (bR) in mixed micelles using SDS as a denaturant. In an effort to confirm that folded bR and SDS-denatured bR reach the same conformational equilibrium, we found that bR folding is significantly slower than has been previously known. Interrogation of the effect of the experimental variables on folding kinetics reveals that the rate of folding is dependent not only on the mole fraction of SDS but also on the molar concentrations of mixed micelle components, a variable that was not controlled in the previous study of bR folding kinetics. Moreover, when the molar concentrations of mixed micelle components are fixed at the concentrations commonly employed for bR equilibrium studies, conformational relaxation in the transition zone is slower than hydrolysis of the retinal Schiff base. As a result, the conformational equilibrium between folded bR and SDS-denatured bR cannot be achieved under the conventional condition. Our finding suggests that the molar concentrations of mixed micelle components are important experimental variables in the investigation of the kinetics and thermodynamics of bR folding and should be accounted for to ensure the accurate assessment of the conformational equilibrium of bR without the interference of retinal hydrolysis. PMID- 22095726 TI - Pressure-overload-induced subcellular relocalization/oxidation of soluble guanylyl cyclase in the heart modulates enzyme stimulation. AB - RATIONALE: Soluble guanylyl cyclase (sGC) generates cyclic guanosine monophophate (cGMP) upon activation by nitric oxide (NO). Cardiac NO-sGC-cGMP signaling blunts cardiac stress responses, including pressure-overload-induced hypertrophy. The latter itself depresses signaling through this pathway by reducing NO generation and enhancing cGMP hydrolysis. OBJECTIVE: We tested the hypothesis that the sGC response to NO also declines with pressure-overload stress and assessed the role of heme-oxidation and altered intracellular compartmentation of sGC as potential mechanisms. METHODS AND RESULTS: C57BL/6 mice subjected to transverse aortic constriction (TAC) developed cardiac hypertrophy and dysfunction. NO-stimulated sGC activity was markedly depressed, whereas NO- and heme-independent sGC activation by BAY 60-2770 was preserved. Total sGCalpha(1) and beta(1) expression were unchanged by TAC; however, sGCbeta(1) subunits shifted out of caveolin enriched microdomains. NO-stimulated sGC activity was 2- to 3-fold greater in Cav3-containing lipid raft versus nonlipid raft domains in control and 6-fold greater after TAC. In contrast, BAY 60-2770 responses were >10 fold higher in non Cav3 domains with and without TAC, declining about 60% after TAC within each compartment. Mice genetically lacking Cav3 had reduced NO- and BAY-stimulated sGC activity in microdomains containing Cav3 for controls but no change within non Cav3-enriched domains. CONCLUSIONS: Pressure overload depresses NO/heme-dependent sGC activation in the heart, consistent with enhanced oxidation. The data reveal a novel additional mechanism for reduced NO-coupled sGC activity related to dynamic shifts in membrane microdomain localization, with Cav3-microdomains protecting sGC from heme-oxidation and facilitating NO responsiveness. Translocation of sGC out of this domain favors sGC oxidation and contributes to depressed NO-stimulated sGC activity. PMID- 22095727 TI - Circadian dependence of infarct size and left ventricular function after ST elevation myocardial infarction. AB - RATIONALE: In rodents, infarct size after ischemia/reperfusion exhibits a circadian dependence on the time of coronary occlusion. It is not known if a similar circadian dependence of infarct size occurs in humans. OBJECTIVE: To determine if humans exhibit a circadian dependence of infarct size in the setting of ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: A retrospective analysis of 1031 patients with STEMI referred for primary percutaneous coronary intervention with known ischemic times between 1 and 6 hours identified 165 patients with occluded arteries on presentation without evidence of preinfarction angina or collateral blood flow. Both ischemic duration and angiographic area at risk were not dependent on time of infarct onset. We observed that the extent of infarct size measured by creatine kinase release was significantly associated with time of day onset of infarction (P<0.0001). The greatest myocardial injury occurred at 1:00 am onset of ischemia and 5:00 am onset of reperfusion, with the peak creatine kinase measured at the peak of the curve being 82% higher than that recorded at the trough. Similarly, left ventricular ejection fraction measured within 2 days of infarction was also dependent on time of onset of STEMI with the absolute left ventricular ejection fraction at peak >7% higher than at trough (43% vs 51%; P<0.03). These findings were supported by a subgroup of patients (n = 45) who underwent cardiac MRI measurements of infarct size and area-at-risk measurements. CONCLUSIONS: The results of this study demonstrate for the first time in humans that myocardial infarct size and left ventricular function after STEMI have a circadian dependence on the time of day onset of ischemia. PMID- 22095728 TI - Acidosis dilates brain parenchymal arterioles by conversion of calcium waves to sparks to activate BK channels. AB - RATIONALE: Acidosis is a powerful vasodilator signal in the brain circulation. However, the mechanisms by which this response occurs are not well understood, particularly in the cerebral microcirculation. One important mechanism to dilate cerebral (pial) arteries is by activation of large-conductance, calcium-sensitive potassium (BK(Ca)) channels by local Ca(2+) signals (Ca(2+) sparks) through ryanodine receptors (RyRs). However, the role of this pathway in the brain microcirculation is not known. OBJECTIVE: The objectives of this study were to determine the mechanism by which acidosis dilates brain parenchymal arterioles (PAs) and to elucidate the roles of RyRs and BK(Ca) channels in this response. METHODS AND RESULTS: Internal diameter and vascular smooth muscle cell Ca(2+) signals were measured in isolated pressurized murine PAs, using imaging techniques. In physiological pH (7.4), vascular smooth muscle cells exhibited primarily RyR-dependent Ca(2+) waves. Reducing external pH from 7.4 to 7.0 in both normocapnic and hypercapnic conditions decreased Ca(2+) wave activity, and dramatically increased Ca(2+) spark activity. Acidic pH caused a dilation of PAs which was inhibited by about 60% by BK(Ca) channel or RyR blockers, in a nonadditive manner. Similarly, dilator responses to acidosis were reduced by nearly 60% in arterioles from BK(Ca) channel knockout mice. Dilations induced by acidic pH were unaltered by inhibitors of K(ATP) channels or nitric oxide synthase. CONCLUSIONS: These results support the novel concept that acidification, by converting Ca(2+) waves to sparks, leads to the activation of BK(Ca) channels to induce dilation of cerebral PAs. PMID- 22095730 TI - Dominant-negative control of cAMP-dependent IKs upregulation in human long-QT syndrome type 1. AB - RATIONALE: The mutation A341V in the S6 transmembrane segment of KCNQ1, the alpha subunit of the slowly activating delayed-rectifier K(+) (I(Ks)) channel, predisposes to a severe long-QT1 syndrome with sympathetic-triggered ventricular tachyarrhythmias and sudden cardiac death. OBJECTIVE: Several genetic risk modifiers have been identified in A341V patients, but the molecular mechanisms underlying the pronounced repolarization phenotype, particularly during beta adrenergic receptor stimulation, remain unclear. We aimed to elucidate these mechanisms and provide new insights into control of cAMP-dependent modulation of I(Ks). METHODS AND RESULTS: We characterized the effects of A341V on the I(Ks) macromolecular channel complex in transfected Chinese hamster ovary cells and found a dominant-negative suppression of cAMP-dependent Yotiao-mediated I(Ks) upregulation on top of a dominant-negative reduction in basal current. Phosphomimetic substitution of the N-terminal position S27 with aspartic acid rescued this loss of upregulation. Western blot analysis showed reduced phosphorylation of KCNQ1 at S27, even for heterozygous A341V, suggesting that phosphorylation defects in some (mutant) KCNQ1 subunits can completely suppress I(Ks) upregulation. Functional analyses of heterozygous KCNQ1 WT:G589D and heterozygous KCNQ1 WT:S27A, a phosphorylation-inert substitution, also showed such suppression. Immunoprecipitation of Yotiao with KCNQ1-A341V (in the presence of KCNE1) was not different from wild-type. CONCLUSIONS: Our results indicate the involvement of the KCNQ1-S6 region at/or around A341 in cAMP-dependent stimulation of I(Ks), a process that is under strong dominant-negative control, suggesting that tetrameric KCNQ1 phosphorylation is required. Specific long-QT1 mutations, including heterozygous A341V, disable this regulation. PMID- 22095729 TI - Induction of vascular progenitor cells from endothelial cells stimulates coronary collateral growth. AB - RATIONALE: A well-developed coronary collateral circulation improves the morbidity and mortality of patients following an acute coronary occlusion. Although regenerative medicine has great potential in stimulating vascular growth in the heart, to date there have been mixed results, and the ideal cell type for this therapy has not been resolved. OBJECTIVE: To generate induced vascular progenitor cells (iVPCs) from endothelial cells, which can differentiate into vascular smooth muscle cells (VSMCs) or endothelial cells (ECs), and test their capability to stimulate coronary collateral growth. METHODS AND RESULTS: We reprogrammed rat ECs with the transcription factors Oct4, Klf4, Sox2, and c-Myc. A population of reprogrammed cells was derived that expressed pluripotent markers Oct4, SSEA-1, Rex1, and AP and hemangioblast markers CD133, Flk1, and c-kit. These cells were designated iVPCs because they remained committed to vascular lineage and could differentiate into vascular ECs and VSMCs in vitro. The iVPCs demonstrated better in vitro angiogenic potential (tube network on 2-dimensional culture, tube formation in growth factor reduced Matrigel) than native ECs. The risk of teratoma formation in iVPCs is also reduced in comparison with fully reprogrammed induced pluripotent stem cells (iPSCs). When iVPCs were implanted into myocardium, they engrafted into blood vessels and increased coronary collateral flow (microspheres) and improved cardiac function (echocardiography) better than iPSCs, mesenchymal stem cells, native ECs, and sham treatments. CONCLUSIONS: We conclude that iVPCs, generated by partially reprogramming ECs, are an ideal cell type for cell-based therapy designed to stimulate coronary collateral growth. PMID- 22095731 TI - Comparison of common lignin methods and modifications on forage and lignocellulosic biomass materials. AB - BACKGROUND: A variety of methods have been developed for estimating lignin concentration within plant materials. The objective of this study was to compare the lignin concentrations produced by six methods on a diverse population of forage and biomass materials and to examine the relationship between these concentrations and the portions of these materials that are available for utilisation by livestock or for ethanol conversion. RESULTS: Several methods produced lignin concentrations that were highly correlated with the digestibility of the forages, but there were few relationships between these methods and the available carbohydrate of the biomass materials. The use of Na2SO3 during preparation of residues for hydrolysis resulted in reduced lignin concentrations and decreased correlation with digestibility of forage materials, particularly the warm-season grasses. CONCLUSION: There were several methods that were well suited for predicting the digestible portion of forage materials, with the acid detergent lignin and Klason lignin method giving the highest correlation across the three types of forage. The continued use of Na2SO3 during preparation of Van Soest fibres needs to be evaluated owing to its ability to reduce lignin concentrations and effectiveness in predicting the utilisation of feedstuffs and feedstocks. Because there was little correlation between the lignin concentration and the biomass materials, there is a need to examine alternative or develop new methods to estimate lignin concentrations that may be used to predict the availability of carbohydrates for ethanol conversion. PMID- 22095732 TI - The reaction mechanism of Cytochrome P450 NO reductase: a detailed quantum mechanics/molecular mechanics study. AB - A detailed QM/MM study on the reaction mechanism of Cytochrome P450 NO reductase is reported. Two reaction pathways connecting the two well-characterized intermediates as well as two putative intermediates that represent the unknown third intermediate are explored, with emphasis on the unusual direct reduction of the enzymatic active site by the cofactor NADH. Activation barriers and kinetic isotope effect are calculated and reveal that reduction of the NO-bound species occurs in form of a hydride ion transfer. Furthermore, the impact of different hydrogen bonds in the active site to binding and reactivity of NADH is explored. The calculated kinetic and thermodynamic properties for both modelled pathways are used for the kinetic simulation of the entire reaction course. It is thus shown that the unknown key intermediate is the singlet diradical Fe(III)-NHOH(?). It is also found that the mechanism of the N-N bond formation is spin-recoupling, which is only possible due to the diradical character of the key intermediate. PMID- 22095733 TI - Predicting outcome of inpatient CBT for adolescents with anxious-depressed school absenteeism. AB - Predictors of outcome of inpatient treatment based on manualized cognitive behavioural therapy (CBT) were examined for 147 adolescents with anxious depressed school absenteeism assessed at discharge and at 2 months after the end of treatment. Outcome measures were regular school attendance and a wide variety of mental health problems rated by adolescents and parents. Socio-demographic data, clinical ratings/diagnosis and adolescent-reported and parent-reported mental health problems were examined as predictors. Regression analyses indicated that none of the variables were able to predict regular school attendance in a clinically relevant way. Adolescent-reported and parent-reported mental health problems at intake predicted these symptoms at both discharge and follow-up (R(2) between 0.31 and 0.61). PMID- 22095734 TI - Cyclo[4]naphthobipyrroles: naphthobipyrrole-derived cyclo[8]pyrroles with strong near-infrared absorptions. PMID- 22095737 TI - BMP-7 stimulates early diaphyseal fracture healing in estrogen deficient rats. AB - Estrogen deficiency causes postmenopausal osteoporosis. The relationship between estrogen deficiency and the high failure rate after osteoporotic fracture treatment is unclear, as is the effect of possible interventions, either with anti-resorptive agents or with anabolic agents such as bone morphogenetic proteins (BMPs). To investigate the influence of estrogen deficiency as well as the effect of early intervention, forty female wistar rats underwent ovarectomy (OVX) followed by low calcium diet. Ten rats underwent sham operations, followed by normal diet. After 6 weeks, a closed midshaft femoral fracture was induced. Ten animals received a systemic bisphosphonate injection, 10 injection of BMP-7 in the fracture, and 10 a combination. All then received a normal diet. After 2 weeks healing was evaluated using radiographs, CT, biomechanical testing, and histology. Radiography showed significant increase of bridging in groups treated with BMP-7. Callus volume was higher in these groups. Bending stiffness and strength were similar between OVX and sham, and not influenced by bisphosphonates. Significant increase was seen in groups treated with BMP-7. Histology was in accordance with other endpoints. Early fracture healing was not affected by estrogen deficiency. While no beneficiary effect of bisphosphonate treatment was found, injection of BMP-7 stimulated healing in ovarectomized rats. PMID- 22095736 TI - Regeneration of the heart. AB - The death of cardiac myocytes diminishes the heart's pump function and is a major cause of heart failure, one of the dominant causes of death worldwide. Other than transplantation, there are no therapies that directly address the loss of cardiac myocytes, which explains the current excitement in cardiac regeneration. The field is evolving in two important directions. First, although endogenous mammalian cardiac regeneration clearly seems to decline rapidly after birth, it may still persist in adulthood. The careful elucidation of the cellular and molecular mechanisms of endogenous heart regeneration may therefore provide an opportunity for developing therapeutic interventions that amplify this process. Second, recent breakthroughs have enabled reprogramming of cells that were apparently terminally differentiated, either by dedifferentiation into pluripotent stem cells or by transdifferentiation into cardiac myocytes. These achievements challenge our conceptions of what is possible in terms of heart regeneration. In this review, we discuss the current status of research on cardiac regeneration, with a focus on the challenges that hold back therapeutic development. PMID- 22095738 TI - Breathing instability in Joubert syndrome. PMID- 22095739 TI - Cofactor-binding sites in proteins of deviating sequence: comparative analysis and clustering in torsion angle, cavity, and fold space. AB - Small molecules are recognized in protein-binding pockets through surface-exposed physicochemical properties. To optimize binding, they have to adopt a conformation corresponding to a local energy minimum within the formed protein ligand complex. However, their conformational flexibility makes them competent to bind not only to homologous proteins of the same family but also to proteins of remote similarity with respect to the shape of the binding pockets and folding pattern. Considering drug action, such observations can give rise to unexpected and undesired cross reactivity. In this study, datasets of six different cofactors (ADP, ATP, NAD(P)(H), FAD, and acetyl CoA, sharing an adenosine diphosphate moiety as common substructure), observed in multiple crystal structures of protein-cofactor complexes exhibiting sequence identity below 25%, have been analyzed for the conformational properties of the bound ligands, the distribution of physicochemical properties in the accommodating protein-binding pockets, and the local folding patterns next to the cofactor-binding site. State of-the-art clustering techniques have been applied to group the different protein cofactor complexes in the different spaces. Interestingly, clustering in cavity (Cavbase) and fold space (DALI) reveals virtually the same data structuring. Remarkable relationships can be found among the different spaces. They provide information on how conformations are conserved across the host proteins and which distinct local cavity and fold motifs recognize the different portions of the cofactors. In those cases, where different cofactors are found to be accommodated in a similar fashion to the same fold motifs, only a commonly shared substructure of the cofactors is used for the recognition process. PMID- 22095740 TI - Analysis of transcriptomic and proteomic profiles demonstrates improved Madin Darby canine kidney cell function in a renal microfluidic biochip. AB - We have evaluated the influence of the microfluidic environment on renal cell functionality. For that purpose, we performed a time lapse transcriptomic and proteomic analysis in which we compared gene and protein expressions of Madin Darby canine kidney cells after 24 h and 96 h of culture in both microfluidic biochips and plates. The transcriptomic and proteomic integration revealed that the ion transporters involved in calcium, phosphate, and sodium homoeostasis and several genes involved in H(+) transporters and pH regulation were up-regulated in microfluidic biochips. Concerning drug metabolism, we found Phase I (CYP P450), Phase II enzymes (GST), various multidrug resistance genes (MRP), and Phase III transporters (SLC) were also up-regulated in the biochips. Furthermore, the study shows that those inductions were correlated with the induction of the Ahr and Nrf-2 dependent pathways, which results in a global cytoprotective response induced by the microenvironment. However, there was no apoptosis situation or cell death in the biochips. Microfluidic biochips may thus provide an important insight into exploring xenobiotic injury and transport modifications in this type of bioartificial microfluidic kidney. Finally, the investigation demonstrated that combining the transcriptomic and proteomic analyses obtained from a cell "on chip" culture would provide a pertinent new tool in the mechanistic interpretation of cellular mechanisms for predicting kidney cell toxicity and renal clearance in vitro. PMID- 22095741 TI - Use of enzyme inhibitors to evaluate the conversion pathways of ester and amide prodrugs: a case study example with the prodrug ceftobiprole medocaril. AB - An approach was developed that uses enzyme inhibitors to support the assessment of the pathways that are responsible for the conversion of intravenously administered ester and amide prodrugs in different biological matrices. The methodology was applied to ceftobiprole medocaril (BAL5788), the prodrug of the cephalosporin antibiotic, ceftobiprole. The prodrug was incubated in plasma, postmitochondrial supernatant fractions from human liver (impaired and nonimpaired), kidney, and intestine as well as erythrocytes, in the presence and absence of different enzyme inhibitors (acetylcholinesterase, pseudocholinesterase, retinyl palmitoyl hydrolase, serine esterases, amidases, and cholinesterase). Hydrolysis was rapid, extensive, and not dependent on the presence of beta-nicotinamide-adenine dinucleotide phosphate (reduced form) in all matrices tested, suggesting the involvement of carboxylesterases but not P450 enzymes. Hydrolysis in healthy human plasma was rapid and complete and only partially inhibited in the presence of paraoxonase inhibitors or in liver from hepatic impaired patients, suggesting involvement of nonparaoxonase pathways. The results demonstrate the utility of this approach in confirming the presence of multiple conversion pathways of intravenously administered prodrugs and in the case of BAL5788 demonstrated that this prodrug is unlikely to be affected by genetic polymorphisms, drug interactions, or other environmental factors that might inhibit or induce the enzymes involved in its conversion. PMID- 22095742 TI - MiR-17-92 cluster regulates cell proliferation and collagen synthesis by targeting TGFB pathway in mouse palatal mesenchymal cells. AB - Elongation and elevation of palatal shelves, mainly caused by proliferation and extra-cellular matrix synthesis of palatal mesenchymal cells (PMCs), are essential for normal palatal development. Transforming growth factor beta (TGFB) pathway could induce proliferation inhibition and collagen synthesis in PMCs. Recent studies found that miRNA-17-92 (miR-17-92) cluster, including miR-17, miR 18a, miR-19a, miR-20a, miR-19b, and miR-92a, expressed in the 1st bronchial arch of mouse embryos during the period of palatal shelf elongation and elevation, and directly targeted TGFB pathway in cancer cell lines. Whether miR-17-92 cluster expresses and targets TGFB pathway in PMCs has not yet been studied. Using quantitative real-time RT-PCR, we found that miR-17-92 expressed in PMCs and decreased from embryonic day (E) 12 to E14 in palatal shelves. MTT assay and Western blot showed that miR-17-92 inhibited TGFB1 induced proliferation inhibition and collagen synthesis in PMCs by decreasing TGFBR2, SMAD2, and SMAD4 protein level. Further luciferase assay showed that miR-17 and miR-20a directly targeted 3'UTR of TGFBR2, and that miR-18a directly targeted 3'UTR of SMAD2 and SMAD4. We thus conclude that miR-17-92 cluster could inhibit TGFB pathway induced proliferation inhibition and collagen synthesis in PMCs by directly targeting TGFBR2, SMAD2, and SMAD4. PMID- 22095743 TI - Modeling large regions in proteins: applications to loops, termini, and folding. AB - Template-based methods for predicting protein structure provide models for a significant portion of the protein but often contain insertions or chain ends (InsEnds) of indeterminate conformation. The local structure prediction "problem" entails modeling the InsEnds onto the rest of the protein. A well-known limit involves predicting loops of <=12 residues in crystal structures. However, InsEnds may contain as many as ~50 amino acids, and the template-based model of the protein itself may be imperfect. To address these challenges, we present a free modeling method for predicting the local structure of loops and large InsEnds in both crystal structures and template-based models. The approach uses single amino acid torsional angle "pivot" moves of the protein backbone with a C(beta) level representation. Nevertheless, our accuracy for loops is comparable to existing methods. We also apply a more stringent test, the blind structure prediction and refinement categories of the CASP9 tournament, where we improve the quality of several homology based models by modeling InsEnds as long as 45 amino acids, sizes generally inaccessible to existing loop prediction methods. Our approach ranks as one of the best in the CASP9 refinement category that involves improving template-based models so that they can function as molecular replacement models to solve the phase problem for crystallographic structure determination. PMID- 22095744 TI - Modulation of human mesenchymal stem cell function in a three-dimensional matrix promotes attenuation of adverse remodelling after myocardial infarction. AB - The application of tissue engineering (TE) practices for cell delivery offers a unique approach to cellular cardiomyoplasty. We hypothesized that human mesenchymal stem cells (hMSCs) applied to the heart in a collagen matrix would outperform the same cells grown in a monolayer and directly injected for cardiac cell replacement after myocardial infarction in a rat model. When hMSC patches were transplanted to infarcted hearts, several measures for left ventricle (LV) remodelling and function were improved, including fractional area change, wall thickness, -dP/dt and LV end-diastolic pressure. Neovessel formation throughout the LV infarct wall after hMSC patch treatment increased by 37% when compared to direct injection of hMSCs. This observation was correlated with increased secretion of angiogenic factors, with accompanying evidence that these factors enhanced vessel formation (30% increase) and endothelial cell growth (48% increase) in vitro. These observations may explain the in vivo observations of increased vessel formation and improved cardiac function with patch-mediated cell delivery. Although culture of hMSC in collagen patches enhanced angiogenic responses, there was no effect on cell potency or viability. Therefore, hMSCs delivered as a cardiac patch showed benefits above those derived from monolayers and directly injected. hMSCs cultured and delivered within TE constructs may represent a good option to maximize the effects of cellular cardiomyoplasty. PMID- 22095745 TI - Body composition analysis of obesity and hepatic steatosis in mice by relaxation compensated fat fraction (RCFF) MRI. AB - PURPOSE: To develop and validate a quantitative magnetic resonance imaging (MRI) methodology for phenotyping animal models of obesity and fatty liver disease on 7T small animal MRI scanners. MATERIALS AND METHODS: A new MRI acquisition and image analysis technique, relaxation-compensated fat fraction (RCFF), was developed and validated by both magnetic resonance spectroscopy and histology. This new RCFF technique was then used to assess lipid biodistribution in two groups of mice on either a high-fat (HFD) or low-fat (LFD) diet. RESULTS: RCFF demonstrated excellent correlation in phantom studies (R(2) = 0.99) and in vivo compared to histological evaluation of hepatic triglycerides (R(2) = 0.90). RCFF images provided robust fat fraction maps with consistent adipose tissue values (82% +/- 3%). HFD mice exhibited significant increases in peritoneal and subcutaneous adipose tissue volumes in comparison to LFD controls (peritoneal: 6.4 +/- 0.4 cm(3) vs. 0.7 +/- 0.2, P < 0.001; subcutaneous: 14.7 +/- 2.0 cm(3) vs. 1.2 +/- 0.3 cm(3) , P < 0.001). Hepatic fat fractions were also significantly different between HFD and LFD mice (3.1% +/- 1.7% LFD vs. 27.2% +/- 5.4% HFD, P = 0.002). CONCLUSION: RCFF can be used to quantitatively assess adipose tissue volumes and hepatic fat fractions in rodent models at 7T. PMID- 22095746 TI - Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging. AB - The neural substrate underlying cognitive impairments after chemotherapy is largely unknown. Here, we investigated very late (>9 years) effects of adjuvant high-dose chemotherapy on brain white and gray matter in primary breast cancer survivors (n = 17) with multimodal magnetic resonance imaging (MRI). A group of breast cancer survivors who did not receive chemotherapy was scanned for comparison (n = 15). Neuropsychological tests demonstrated cognitive impairments in the chemotherapy group. Diffusion tensor imaging (DTI) with tract-based spatial statistics showed that chemotherapy was associated with focal changes in DTI values indicative for reduced white matter integrity. Single voxel proton MR spectroscopy (1H-MRS) in the left centrum semiovale (white matter) showed a reduction of N-acetylasparate/creatine indicative of axonal injury. Voxel-based morphometry demonstrated a reduction of gray matter volume that overlapped with fMRI hypoactivation (as reported in a previous publication) in posterior parietal areas and colocalized with DTI abnormalities. Also, DTI correlated with 1H-MRS only in the chemotherapy group. These results converge to suggest that high-dose adjuvant chemotherapy for breast cancer is associated with long-term injury to white matter, presumably reflecting a combination of axonal degeneration and demyelination, and damage to gray matter with associated functional deficits. Hormonal treatment with tamoxifen may also have contributed to the observed effects, although results from other studies indicate that it is unlikely that tamoxifen is solely or largely responsible. Using this multimodality approach we provide for the first time insight into the neural substrate underlying cognitive impairments following systemic administration of cytotoxic agents many years after treatment. PMID- 22095747 TI - MQD--multiplex-quadrature detection in multi-dimensional NMR. AB - With multiplex-quadrature detection (MQD) the tasks of coherence selection and quadrature separation in N-dimensional heteronuclear NMR experiments are merged. Thus the number of acquisitions required to achieve a desired resolution in the indirect dimensions is significantly reduced. The minimum number of transients per indirect data point, which have to be combined to give pure-phase spectra, is thus decreased by a factor (3/4)(N-1). This reduction is achieved without adjustable parameters. We demonstrate the advantage by MQD 3D HNCO and HCCH-TOCSY spectra affording the same resolution and the same per-scan sensitivity as standard phase-cycled ones, but obtained in only 56 % of the usual time and by resolution improvements achieved in the same amount of time. PMID- 22095748 TI - Nutritional composition of Zizyphus lotus L. seeds. AB - BACKGROUND: Zizyphus lotus seeds are an unutilized source of vegetable oil and protein and nothing has been reported on their physicochemical characteristics which would indicate the potential uses of these seeds. RESULTS: The percentage composition of the Zizyphus lotus seeds is (on a dry-weight basis): ash 1.05%, oil 32.92%, protein 19.11%, total carbohydrate 40.87% and moisture 6.05%. Calcium, potassium and magnesium constitute the major minerals of Zizyphus lotus seeds. The seed proteins are rich in threonine, glutamic acid, leucine, arginine and aspartic acid (26.73%, 17.28%, 13.11%, 9.47% and 7.76%, respectively). The main fatty acids of the oil are oleic (61.93%), linoleic (18.31%) and palmitic (9.14%) acids. Glycerol trioleate (OOO; O: oleic acid) was the most abundant triacylglycerol, representing 26.48% of the total triacyglycerols. beta Tocopherol was the major tocopherol (130.47 mg 100 g(-1) ). This oil was rich in Delta7-campestrol and beta-sitosterol (147.82 and 82.10 mg 100 g(-1) oil), respectively. CONCLUSION: Zizyphus lotus seeds are rich in fat and protein which are of potential industrial significance. In addition, Zizyphus lotus L. seed oil contained many bioactive compounds. This fact is of great economic interest owing to several applications of Zizyphus lotus L. seeds in the food, cosmetics and medicinal industries. PMID- 22095749 TI - Palladium-catalyzed allylic alkylation of carboxylic acid derivatives: N acyloxazolinones as ester enolate equivalents. PMID- 22095750 TI - Use of UpToDate and outcomes in US hospitals. AB - BACKGROUND: Computerized clinical knowledge mana-gement systems hold enormous potential for improving quality and efficiency. However, their impact on clinical practice is not well known. OBJECTIVE: To examine the impact of UpToDate on outcomes of care. DESIGN: Retrospective study. SETTING: National sample of US inpatient hospitals. PATIENTS: Fee-for-service Medicare beneficiaries. INTERVENTION: Adoption of UpToDate in US hospitals. MEASUREMENT: Risk-adjusted lengths of stay, mortality rates, and quality performance. RESULTS: We found that patients admitted to hospitals using UpToDate had shorter lengths of stay than patients admitted to non-UpToDate hospitals overall (5.6 days vs 5.7 days; P < 0.001) and among 6 prespecified conditions (range, -0.1 to -0.3 days; P < 0.001 for each). Further, patients admitted to UpToDate hospitals had lower risk adjusted mortality rate for 3 of the 6 conditions (range, -0.1% to -0.6% mortality reduction; P < 0.05). Finally, hospitals with UpToDate had better quality performance for every condition on the Hospital Quality Alliance metrics. In subgroup analyses, we found that it was the smaller hospitals and the non teaching hospitals where the benefits of the UpToDate seemed most pronounced, compared to the larger, teaching institutions where the benefits of UpToDate seemed small or nonexistent. CONCLUSIONS: We found a very small but consistent association between use of UpToDate and reduced length of stay, lower risk adjusted mortality rates, and better quality performance, at least in the smaller, non-teaching institutions. These findings may suggest that computerized tools such as UpToDate could be helpful in improving care. PMID- 22095751 TI - An experimental glenoid rim strain analysis for an improved reverse anatomy shoulder implant fixation. AB - Loosening of glenoid components in TSA is a main cause of failure. In reverse anatomy TSA designs used for unstable joints, fixation is particularly demanding. Strains developed around the glenoid rim of biomechanical sawbone scapulae implanted with (a) the original fixed-fulcrum Bayley-Walker glenoid prosthesis in current clinical use, and (b) a revised version with conical cross-section, were compared. The conical shape of the revised design was hypothesized to produce greater strains in the glenoid rim than the original tapered screw design. The 2D strain field at three accessible locations around the rim of each scapula was measured with three-element rosette strain gauges for two types of simulated cancellous bone fill under applied physiologically relevant loads. The average strain energy densities around the rim for the conical design were greater than for the original design by a factor of 1.55-2.25 for all loading conditions. Results indicate that a significantly greater proportion of load was directed toward cortical bone in the conical design, thus promoting cortical bone loading. PMID- 22095753 TI - Re: indeterminate 1-2 cm nodules found on hepatocellular carcinoma surveillance: biopsy for all, some, or none? PMID- 22095752 TI - AKAP2 anchors PKA with aquaporin-0 to support ocular lens transparency. AB - A decline in ocular lens transparency known as cataract afflicts 90% of individuals by the age 70. Chronic deterioration of lens tissue occurs as a pathophysiological consequence of defective water and nutrient circulation through channel and transporter proteins. A key component is the aquaporin-0 (AQP0) water channel whose permeability is tightly regulated in healthy lenses. Using a variety of cellular and biochemical approaches we have discovered that products of the A-kinase anchoring protein 2 gene (AKAP2/AKAP-KL) form a stable complex with AQP0 to sequester protein kinase A (PKA) with the channel. This permits PKA phosphorylation of serine 235 within a calmodulin (CaM)-binding domain of AQP0. The additional negative charge introduced by phosphoserine 235 perturbs electrostatic interactions between AQP0 and CaM to favour water influx through the channel. In isolated mouse lenses, displacement of PKA from the AKAP2 AQP0 channel complex promotes cortical cataracts as characterized by severe opacities and cellular damage. Thus, anchored PKA modulation of AQP0 is a homeostatic mechanism that must be physically intact to preserve lens transparency. PMID- 22095754 TI - A highly alpha-stereoselective synthesis of oligosaccharide fragments of the Vi antigen from Salmonella typhi and their antigenic activities. AB - In this paper, a convenient approach to the synthesis of the repeating alpha-(1 >4)-linked N-acetyl galactosaminuronic acid units from the capsular polysaccharide of Salmonella typhi is reported. The exclusively alpha stereoselective glycosylation reactions were achieved by using oxazolidinone protected glycosides as building blocks based on a pre-activation protocol. Di-, tri-, and tetrasaccharides were prepared by this short and efficient approach in high yields. The enzyme-linked immunosorbent assay experiments show that our synthetic tri- and tetrasaccharide had much higher antigenic activities than previously reported ones in the inhibition of antibody binding by the native polysaccharide. The results demonstrate that the antigenic activities of saccharides can be strengthened greatly by increasing the number of acetyl groups present. PMID- 22095755 TI - Environmental tobacco smoke and Parkinson's disease. AB - BACKGROUND: Parkinson's disease is inversely associated with cigarette smoking, but its relation with passive smoking or environmental tobacco smoke exposure is rarely examined. METHODS: Within a case-control study, we assessed the association between Parkinson's disease and living or working with active smokers. Cases were newly diagnosed with idiopathic Parkinson's disease (n = 154) from western Washington State in 2002-2008. Age- and sex-matched controls (n = 173) were neurologically normal and unrelated to cases. RESULTS: Compared with never active or passive tobacco smokers, we observed reduced Parkinson's disease risks for ever passive only smokers (OR, 0.34; 95% CI, 0.16-0.73), similar to those for ever active smokers (OR, 0.35; 95% CI, 0.17-0.73). Among persons whose only tobacco smoke exposure was passive smoking at home, risk was inversely associated with years exposed. CONCLUSIONS: These observations parallel those well established for active smoking. However, it remains unresolved whether a true protective effect of tobacco smoke, generally detrimental to health, underlies these associations. PMID- 22095757 TI - Nanocluster budesonide formulations enhance drug delivery through endotracheal tubes. AB - The pulmonary system is an attractive route for drug delivery because the lungs have a large accessible surface area for treatment. For ventilated patients, an endotracheal tube is required for delivering drugs into the lungs. Such tubes are generally poor conduits for delivering traditional aerosol formulations. Both the formulation and the properties of the endotracheal tube are important effectors of delivery efficiency. In this study, agglomerates of budesonide nanoparticles (NanoClusters) were formulated with or without l-leucine or lactose. Teflon tubing was compared with commercial endotracheal tubes as a conduit for delivering budesonide powders into a cascade impactor. The effects of volumetric flow rate, tube size, and humidity were also investigated. NanoCluster budesonide (NC-Bud) formulations had a considerably higher emitted dose and fine particle fraction compared with stock budesonide and the commercial Flexhaler powder when applied through endotracheal tubes. Tubing material did not significantly affect powder performance, but decreasing tubing diameter or increasing volumetric flow rates yielded a smaller mass median aerodynamic diameter for NC-Bud. Engineered NC-Bud powders may dramatically improve drug delivery through endotracheal tubes when using proper ventilator settings. PMID- 22095756 TI - Mitochondrial and liver oxidative stress alterations induced by N-butyl-N-(4 hydroxybutyl)nitrosamine: relevance for hepatotoxicity. AB - The most significant toxicological effect of nitrosamines like N-butyl-N-(4 hydroxybutyl)nitrosamine (BBN) is their carcinogenic activity, which may result from exposure to a single large dose or from chronic exposure to relatively small doses. However, its effects on mitochondrial liver bioenergetics were never investigated. Liver is the principal organ responsible for BBN metabolic activation, and mitochondria have a central function in cellular energy production, participating in multiple metabolic pathways. Therefore any negative effect on mitochondrial function may affect cell viability. In the present work, ICR male mice were given 0.05% of BBN in drinking water for a period of 12 weeks and were sacrificed one week later. Mitochondrial physiology was characterized in BBN- and control-treated mice. Transmembrane electric potential developed by mitochondria was significantly affected when pyruvate-malate was used, with an increase in state 4 respiration observed for pyruvate-malate (46%) and succinate (38%). A decrease in the contents of one subunit of mitochondrial complex I and in one subunit of mitochondrial complex IV was also observed. In addition, the activity of both complexes I and II was also decreased by BBN treatment. The treatment with BBN increases the susceptibility of liver mitochondria to the opening of the mitochondrial permeability transition pore. This susceptibility could be related with the increase in the production of H2 O2 by mitochondria and increased oxidative stress confirmed by augmented susceptibility to lipid peroxidation. These results lead to the conclusion that hepatic mitochondria are one primary target for BBN toxic action during liver metabolism. PMID- 22095758 TI - Polymeric photoresist nanoparticles: light-induced degradation of hydrophobic polymers in aqueous dispersion. AB - Nanoparticles consisting of a photoreactive polymer able to radically switch its hydrophobicity are successfully prepared by miniemulsion polymerization. Irradiation with UV light causes degradation of the particles where at complete dissolution is achieved by changing the initial hydrophobic photoresist polymer into hydrophilic poly(methacrylic acid). Incorporation of the fluorescence sensitive Nile red serves as a solvatochromic probe to study the particle degradation. Diffusion of either Nile red out from or water into the former hard spherical nanoparticles is studied and not only renders the described material an ideal system for applications, where in situ dissolution of nanoparticles may be needed, but also bears the additional advantage of performing controlled burst release. PMID- 22095759 TI - Assessing agreement with repeated measures for random observers. AB - Agreement studies are often concerned with assessing whether different observers for measuring responses on the same subject or sample can produce similar results. The concordance correlation coefficient (CCC) is a popular index for assessing the closeness among observers for quantitative measurements. Usually, the CCC is used for data without and with replications based on subject and observer effects only. However, we cannot use this methodology if repeated measurements rather than replications are collected. Although there exist some CCC-type indices for assessing agreement with repeated measurements, there is no CCC for random observers and random time points. In this paper, we propose a new CCC for repeated measures where both observers and time points are treated as random effects. A simulation study demonstrates our proposed methodology, and we use vertebral body data and image data for illustrations. PMID- 22095760 TI - Disproportionality analysis for signal detection of implantable cardioverter defibrillator-related adverse events in the Food and Drug Administration Medical Device Reporting System. AB - BACKGROUND: The Food and Drug Administration (FDA) became aware of lead fracture and inappropriate shock events related to Sprint Fidelis leads in January 2007. The manufacturer announced a voluntary market withdrawal in October 2007. AIM: Our aim was to retrospectively evaluate this safety signal using disproportionality analysis to estimate whether disproportionality analysis could have detected this particular safety signal earlier than actually occurred. MATERIALS AND METHODS: The Manufacturer and User Facility Device Experience (MAUDE) database contains reports on device-related adverse events, of which, FDA receives several hundred thousand every year. For each manufacturer, a list of the top lead brand names was ranked by frequency of reports. We used the Multi item Gamma Poisson Shrinker (MGPS) method for analysis. We isolated 11 top reported implantable cardioverter defibrillator (ICD) lead brand names. Using MGPS methodology, we calculated the one-sided 95% lower confidence bound EB05 on the empirical Bayes geometric mean of the reporting ratio. RESULTS: We performed individual MGPS analysis for each of the top reported adverse events in 2006 for ICD leads. Fidelis had the highest EB05 scores for lead fractures and inappropriate shock. DISCUSSION: Through disproportionality analysis of the MAUDE database, we were able to identify known safety signals associated with the Medtronic Sprint Fidelis lead. CONCLUSION: If utilized at the time, this disproportionality analysis would have identified signals earlier for lead fractures, oversensing, high impedance, and inappropriate shock. PMID- 22095761 TI - A one-pot three-segment ligation strategy for protein chemical synthesis. PMID- 22095762 TI - Efficacy of ozone as a fungicidal and detoxifying agent of aflatoxins in peanuts. AB - BACKGROUND: Peanut contamination by fungi is a concern of processors and consumers owing to the association of these micro-organisms with quality deterioration and aflatoxin production. In this study the fungicidal and detoxifying effects of ozone on aflatoxins in peanuts was investigated. Peanut kernels were ozonated at concentrations of 13 and 21 mg L-1 for periods of 0, 24, 48, 72 and 96 h. RESULTS: Ozone was effective in controlling total fungi and potentially aflatoxigenic species in peanuts, with a reduction in colony-forming units per gram greater than 3 log cycles at the concentration of 21 mg L-1 after 96 h of exposure. A reduction in the percentage of peanuts with internal fungal populations was also observed, particularly after exposure to ozone at 21 mg L-1. A reduction in the concentrations of total aflatoxins and aflatoxin B1 of approximately 30 and 25% respectively was observed for kernels exposed to ozone at 21 mg L-1 for 96 h. CONCLUSION: It was concluded that ozone is an important alternative for peanut detoxification because it is effective in controlling potentially aflatoxigenic fungi and also acts in the reduction of aflatoxin levels in kernels. PMID- 22095763 TI - Magnetite nanocrystal clusters with ultra-high sensitivity in magnetic resonance imaging. AB - Magnetic iron oxide particles are widely used as contrast agents to improve the sensitivity of magnetic resonance imaging (MRI). Their efficiency in MRI is usually quantified by transverse relaxivity (r(2)) in solution. Herein, we synthesized a series of magnetite nanocrystal clusters (MNCs) with ultra-high transverse relaxivity by a polyol process and studied the relationship between r(2) and size of the MNCs. The sizes of MNCs can be tuned over a wide range from 13 to 179 nm. The r(2) of MNC suspensions as a function of the size of the cluster was analyzed and compared with a theoretical model. We found that MNCs of 64 nm had an r(2) value of 650 mM(-1) s(-1), which was more than three times that of the commercial contrast agent and was among the highest reported for iron oxide materials. Compared with the theoretical model, the r(2) value of the MNC suspension is approximately 0.93 of the theoretical prediction. Imaging of the MNC suspensions was performed in a clinical 1.5 T MRI instrument and a comparison was made between MNCs and commercial contrast agents. MRI indicated that the decrease of signal intensity induced by MNCs was in proportion to the r(2) value, which was in accordance with theoretical predictions. These results demonstrate that MNCs with ultra-high transverse relaxivity and tunable size are promising candidates for molecular imaging and clinical diagnosis in MRI. PMID- 22095764 TI - The role of RNA in mammalian prion protein conversion. AB - Prion diseases remain a challenge to modern science in the 21st century because of their capacity for transmission without an encoding nucleic acid. PrP(Sc), the infectious and alternatively folded form of the PrP prion protein, is capable of self-replication, using PrP(C), the properly folded form of PrP, as a template. This process is associated with neuronal death and the clinical manifestation of prion-based diseases. Unfortunately, little is known about the mechanisms that drive this process. Over the last decade, the theory that a nucleic acid, such as an RNA molecule, might be involved in the process of prion structural conversion has become more widely accepted; such a nucleic acid would act as a catalyst rather than encoding genetic information. Significant amounts of data regarding the interactions of PrP with nucleic acids have created a new foundation for understanding prion conversion and the transmission of prion diseases. Our knowledge has been enhanced by the characterization of a large group of RNA molecules known as non-coding RNAs, which execute a series of important cellular functions, from transcriptional regulation to the modulation of neuroplasticity. The RNA-binding properties of PrP along with the competition with other polyanions, such as glycosaminoglycans and nucleic acid aptamers, open new avenues for therapy. PMID- 22095765 TI - Joint effects of Epstein-Barr virus and polymorphisms in interleukin-10 and interferon-gamma on breast cancer risk. AB - BACKGROUND: The relationship between Epstein-Barr virus (EBV) and breast cancer (BC) is controversial. Interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) are believed to play a critical role in the host's responses to EBV infection, and their genetic variations may modify the association of EBV with BC risk. METHODS: We examined serum levels of EBV viral capsid antigen (VCA) immunoglobulin A (IgA) and nuclear antigen-1 (EBNA-1) IgA along with the polymorphisms of IL-10 rs1800871 and IFN-gamma rs2069705 in 354 incident BC cases and 504 age-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. RESULTS: VCA IgA and EBNA-1 IgA levels were positively associated with BC risk. IL-10 rs1800871 (TC/CC) was associated with a reduced BC risk (OR, 0.74 [95% CI, 0.55-1.00]) but had no interaction with EBV infection on BC risk. IFN-gamma rs2069705 was not directly associated with BC risk but interacted with EBNA-1 IgA on BC risk. Among women with the CC genotype, EBNA-1 IgA seropositivity significantly increased the risk of BC compared to EBNA-1 IgA seronegativity (OR, 5.14 [95% CI, 1.76-14.98]). CONCLUSIONS: These results suggest that EBV may contribute to the risk of BC and that this contribution may be modified by genetic variations in IFN-gamma. PMID- 22095766 TI - Serum hepatitis B virus-DNA levels correlate with long-term adverse outcomes in spontaneous hepatitis B e antigen seroconverters. AB - BACKGROUND: Hepatitis B e antigen (HBeAg) status and serum hepatitis B virus (HBV) DNA levels are major factors affecting the prognosis of adult HBV carriers; however, the impact of viral load on long-term outcomes after spontaneous HBeAg seroconversion remains unclear. METHODS: A total of 390 spontaneous HBeAg seroconverters with a long-term follow-up were enrolled. Serum HBV-DNA levels at 1 year after HBeAg seroconversion were determined, and their correlation with long-term adverse outcomes was explored. RESULTS: In a mean follow-up of 6.8 years, the average annual incidence rates were 4.4% and 1.9% for HBeAg-negative hepatitis and hepatitis flare, respectively. Compared with patients with HBV-DNA levels <200 IU/mL, the adjusted hazard ratios of HBeAg-negative hepatitis were 2.4 (95% confidence interval, 1.3-4.4), 3.6 (1.8-7.2), and 5.3 (2.8-10.0), respectively, for serum HBV-DNA level of 2000 -2 * 10(4), 2 * 10(4) -2 * 10(5), and >=2 * 10(5) IU/mL. In addition, serum HBV-DNA levels were independently associated with HBeAg-negative hepatitis flare, which confirmed their impact on the immune active hepatitis after HBeAg seroconversion. CONCLUSIONS: HBeAg seroconversion may not always confer favorable outcomes. Serum HBV-DNA levels >=2000 IU/mL at 1 year post HBeAg seroconversion correlate with increased risk of HBeAg-negative hepatitis and hepatitis flare. PMID- 22095767 TI - Management of chronic hepatitis B e antigen-negative disease: another step forward. PMID- 22095768 TI - Rapid full-brain fMRI with an accelerated multi shot 3D EPI sequence using both UNFOLD and GRAPPA. AB - The desire to understand complex mental processes using functional MRI drives development of imaging techniques that scan the whole human brain at a high spatial and temporal resolution. In this work, an accelerated multishot three dimensional echo-planar imaging sequence is proposed to increase the temporal resolution of these studies. A combination of two modern acceleration techniques, UNFOLD and GRAPPA is used in the secondary phase encoding direction to reduce the scan time effectively. The sequence (repetition time of 1.02 s) was compared with standard two-dimensional echo-planar imaging (3 s) and multishot three dimensional echo-planar imaging (3 s) sequences with both block design and event related functional MRI paradigms. With the same experimental setup and imaging time, the temporal resolution improvement with our sequence yields similar activation regions in the block design functional MRI paradigm with slightly increased t-scores. Moreover, additional information on the timing of rapid dynamic changes was extracted from accelerated images for the case of the event related complex mental paradigm. PMID- 22095769 TI - The normal parkin sequence. PMID- 22095770 TI - Dunnett-type inference in the frailty Cox model with covariates. AB - A frequent objective in medical research is the investigation of differences in patient survival between several experimental treatments and one standard treatment. In order to assess these differences statistically, we have to apply adjustments for multiple comparisons to prevent an increased number of false positive findings. The most prominent procedure of this type is the Bonferroni correction, which maintains the error level but leads to conservative results. On the basis of a general statistical framework for simultaneous inference, we propose a new statistical procedure for many-to-one comparisons of treatments with adjustment for covariates for clustered survival data modeled by a frailty Cox model. In contrast to the Bonferroni method, dependencies between estimated effects are taken into account. The resulting simultaneous confidence intervals for the hazard ratios of the experimental treatments compared with a control can be interpreted in terms of both statistical significance and clinical importance. The quality of the new procedure is judged by the coverage probability for the simultaneous confidence intervals. Simulation results show an acceptable performance in balanced and various unbalanced designs. The practical merits are demonstrated by a reanalysis of a chronic myelogeneous leukemia clinical trial. The procedure presented here works well for multiple comparisons with a control with adjustment for covariates for survival data from multicenter clinical trials. PMID- 22095771 TI - Formic acid catalyzed gas-phase reaction of H2O with SO3 and the reverse reaction: a theoretical study. AB - The formic acid catalyzed gas-phase reaction between H(2)O and SO(3) and its reverse reaction are respectively investigated by means of quantum chemical calculations at the CCSD(T)//B3LYP/cc-pv(T+d)z and CCSD(T)//MP2/aug-cc-pv(T+d)z levels of theory. Remarkably, the activation energy relative to the reactants for the reaction of H(2)O with SO(3) is lowered through formic acid catalysis from 15.97 kcal mol(-1) to -15.12 and -14.83 kcal mol(-1) for the formed H(2)O???SO(3) complex plus HCOOH and the formed H(2)O???HCOOH complex plus SO(3), respectively, at the CCSD(T)//MP2/aug-cc-pv(T+d)z level. For the reverse reaction, the energy barrier for decomposition of sulfuric acid is reduced to 3.07 kcal mol(-1) from 35.82 kcal mol(-1) with the aid of formic acid. The results show that formic acid plays a strong catalytic role in facilitating the formation and decomposition of sulfuric acid. The rate constant of the SO(3)+H(2)O reaction with formic acid is 10(5) times greater than that of the corresponding reaction with water dimer. The calculated rate constant for the HCOOH+H(2)SO(4) reaction is about 10(-13) cm(3) molecule(-1) s(-1) in the temperature range 200-280 K. The results of the present investigation show that formic acid plays a crucial role in the cycle between SO(3) and H(2)SO(4) in atmospheric chemistry. PMID- 22095772 TI - Immunosuppressive small molecule discovered by structure-based virtual screening for inhibitors of protein-protein interactions. PMID- 22095773 TI - Social constraints, genetic vulnerability, and mental health following collective stress. AB - A repeat-length polymorphism of the serotonin promoter gene (5-HTTLPR) has been associated with depression and posttraumatic stress disorder (PTSD) in trauma exposed individuals reporting unsupportive social environments. We examine the contributions of the triallelic 5-HTTLPR genotype and social constraints to posttraumatic stress (PTS) symptoms in a national sample following the September 11, 2001 (9/11) terrorist attacks. Saliva was collected by mail from 711 respondents (European American subsample n = 463) of a large national probability sample of 2,729 adults. Respondents completed web-based assessments of pre-9/11 mental and physical health, acute stress 9 to 23 days post-9/11, PTS symptoms, and social constraints on disclosure regarding fears of future terrorist attacks 2-3 years post-9/11. Social constraints were positively associated with PTS symptoms 2-3 years post-9/11. The triallelic 5-HTTLPR genotype was not directly associated with PTS symptoms, but it interacted with social constraints to predict PTS symptoms 2-3 years post-9/11: Social constraints were more strongly associated with PTS symptoms for individuals with any s/lg allele than for homozygous la/la individuals. Constraints on disclosing fears about future terrorism moderate the 5-HTTLPR genotype-PTS symptom association even when indirectly exposed to collective stress. PMID- 22095774 TI - The longitudinal course of PTSD among disaster workers deployed to the World Trade Center following the attacks of September 11th. AB - This study examined the long-term mental health outcomes of 2,960 nonrescue disaster workers deployed to the World Trade Center site in New York City following the September 11, 2001 (9/11) terrorist attacks. Semistructured interviews and standardized self-report measures were used to assess the prevalence of posttraumatic stress disorder (PTSD) and other psychopathology 4 and 6 years after the attacks. Clinician-measured rates of PTSD and partial PTSD 4-years posttrauma were 8.4% and 8.9%, respectively, in a subsample of 727 individuals. Rates decreased to 5.8% and 7.7% for full and partial PTSD 6 years posttrauma. For the larger sample, self-report scores revealed probable PTSD and partial PTSD prevalence to be 4.8% and 3.6% at 4 years, and 2.4% and 1.8% at 6 years. Approximately 70% of workers never met criteria for PTSD. Although PTSD rates decreased significantly over time, many workers remained symptomatic, with others showing delayed-onset PTSD. The strongest predictors of ongoing PTSD 6 years following 9/11 were trauma history (odds ratio (OR) = 2.27, 95% confidence interval (CI) [1.06, 4.85]); the presence of major depressive disorder 1-2 years following the trauma (OR = 2.80, 95% CI [1.17, 6.71]); and extent of occupational exposure (OR = 1.31, 95% CI [1.13, 1.51]). The implications of the findings for both screening and treatment of disaster workers are discussed. PMID- 22095775 TI - Cognitive and emotional contributors to intimate partner violence perpetration following trauma. AB - Exposure to potentially traumatic events often leads to a wide range of interpersonal difficulties, including the perpetration of intimate partner violence. Maladaptive, threat-relevant thoughts and beliefs regarding the trauma or its sequelae can play an important role in a person's emotional and behavioral responses. Among 185 trauma-exposed study participants who were currently in an intimate relationship, levels of maladaptive posttraumatic cognitions were associated with the perpetration of psychological aggression and physical violence in their current relationships. These links were mediated by misappraisal of anger in auditory emotion stimuli and emotion-regulation deficits. Results support a cognitive model of posttraumatic pathology, with implications for clinical intervention and a broad conceptualization of the effects of trauma. PMID- 22095776 TI - Reactions to trauma research among women recently exposed to a campus shooting. AB - Subjective and objective reactions to writing and reading a narrative of their experiences after having been recently exposed to a campus shooting were examined in 58 women. Posttraumatic stress, depression, anxiety symptoms, and physical exposure to the shooting were considered in relation to laboratory indices. The latter used a multimethod approach to index distress; these included subjective (self-report) and objective (heart rate, skin conductance, and cortisol) components. Consistent with prior research, reports of symptoms were significantly positively correlated with subjective distress (r ranged from .35 to .45), but only posttraumatic stress symptoms uniquely predicted subjective distress in regression analyses (partial r = .33). Objective distress, however, was not significantly related to any participant measure. Finally, a clear majority (85%) of participants reported they would participate in the study again. Points of convergence and divergence with prior studies are discussed. PMID- 22095777 TI - Predictors of suicidal ideation in veterans with PTSD related to military sexual trauma. AB - Predictors of suicidal ideation (SI) were examined in a sample of veterans (N = 128) diagnosed with posttraumatic stress disorder (PTSD) related to military sexual trauma. Suicidal ideation was predicted by both depressive symptom severity and posttraumatic symptom severity in separate correlation analyses. When controlling for the effects of depressive and posttraumatic symptom severity on one another in the prediction of SI in a single multiple regression model, however, only depressive symptoms independently predicted SI. These analyses suggest that the contribution of PTSD symptom severity to the prediction of SI is reduced by adding depressive symptoms. Hyperarousal symptom severity, however, was found in a separate multiple regression model to contribute independently to the prediction of SI controlling for depressive symptom severity. PMID- 22095778 TI - Toxicokinetic study of melamine in the presence and absence of cyanuric acid in rats. AB - Several lines of evidence show that the nephrotoxic effect of melamine (MEL) in animals is consistent with combined ingestion of MEL and cyanuric acid (CYA). The aim of the present study was to compare the toxicokinetics of MEL in the presence and absence of CYA, and to elucidate the correlation between toxicity and kinetic properties of MEL. Sprague-Dawley rats were administered a single oral dose of MEL (100 mg kg(-1) ) with or without CYA (100 mg kg(-1) ). Plasma and tissue samples were analyzed by liquid chromatography-tandem mass spectrometric (LC MS/MS) assay. Significant changes in toxicokinetic parameters of MEL such as lower maximum concentration (7.4 +/- 3.5 vs 78.0 +/- 11.0 ug ml(-1) ) and area under curve (94.9 +/- 53.5 vs 295.1 +/- 93.7 ug h ml(-1) ), higher plasma elimination half-life (7.0 +/- 3.3 vs 2.5 +/- 0.3 h) and volume of distribution (11 505.5 +/- 5030.3 vs 1312.7 +/- 337.7 ml kg(-1) ), as well as significantly higher concentration of MEL in rat kidney (2.96-274.15 vs < 1 ug g(-1) ) were detected in the CYA co-administration group when compared with MEL alone group (P < 0.05). The differences in kinetic parameters between the two groups meant that CYA co-administration could lower absorption, slow excretion and induce tissue accumulation of MEL, which correlated well with the generation and development of renal toxicity. In conclusion, co-administration with CYA leads to the alteration of the kinetic characteristics of MEL, which provides an additional explanation for renal toxicity. PMID- 22095779 TI - Rapid determination of lycopene and beta-carotene in tomato by liquid chromatography/electrospray tandem mass spectrometry. AB - BACKGROUND: The tomato fruit is a dietary source of carotenoids, bioactive antioxidant compounds that play an important role in the prevention of degenerative diseases. Several extraction and detection techniques regarding carotenoids in tomatoes can be found in the literature, mainly based on high performance liquid chromatography separation and ultraviolet-visible detection. RESULTS: The best extraction conditions and tandem mass spectrometry (MS) analysis were evaluated: lycopene and beta-carotene were extracted in a cyclohexane/ethyl acetate mixture without the addition of antioxidants, next separated by liquid chromatography on a C(18) column and then determined through electrospray tandem MS. Ionic suppression by the matrix in negative ionisation mode did not allow the analysis of extracts, hence the positive ionisation mode was chosen. Validation parameters demonstrated the suitability for purpose of the analytical method: accuracy, precision, linearity and detection limits were adequate. The method was finally applied to different tomato samples, and differences could be easily highlighted. CONCLUSION: The method was simple, fast and appropriate for the purpose of analysing lycopene and beta-carotene in tomatoes. PMID- 22095780 TI - Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology. AB - The most common inborn error of bile acid metabolism is 3beta-hydroxy-Delta(5) C(27)-steroid oxidoreductase (3beta-HSD) deficiency, a disorder that usually presents in early childhood with hepatic dysfunction. Timely diagnosis of this disorder is crucial because it can be effectively treated with primary bile acid replacement. Here we describe a 24-year-old woman from Iran with cirrhosis of unknown etiology. Her sister and a first cousin died of cirrhosis (ages 19 and 6 years) and another 32-year-old first cousin had a self-limited liver disorder in childhood that resolved at age 9 years. The family history suggested that the affected family members were homozygous for a mutant allele inherited identical by-descent. A genome-wide analysis of 2.4 million single nucleotide polymorphisms was performed to identify regions of homozygosity that were present in the proband and the 32-year-old first cousin, but not in a healthy relative. One of these regions contained the gene encoding 3beta-HSD (HSD3B7). Sequence analysis of HSD3B7 revealed that the proband and her 32-year-old cousin were homozygous for a frameshift mutation (c.45_46del AG, p.T15Tfsx27) in exon 1. The diagnosis of 3beta-HSD deficiency was confirmed by documenting high levels of 3beta-hydroxy Delta(5) bile acids in the serum of the proband and the 32-year-old first cousin using mass spectrometry. To our knowledge, the 32-year-old relative in this family represents the oldest asymptomatic patient with this disorder. CONCLUSION: This study highlights the clinical utility of homozygosity mapping in diagnosing autosomal recessive metabolic disorders. This family illustrates the wide variation in expressivity that occurs in 3beta-HSD deficiency and underscores the need to consider a bile acid synthetic defect as a possible cause of liver disease in adults. PMID- 22095781 TI - Molecular alterations in hepatocarcinogenesis induced by dietary methyl deficiency. AB - A chronic deficiency of major dietary methyl group donors--methionine, choline, folic acid, and vitamin B12--can induce the development of liver cancer in rodents. Feeding methyl-deficient diets causes several molecular alterations, including altered lipid metabolism, oxidative stress, deregulated one-carbon metabolism, and a number of epigenetic abnormalities that result in progressive liver injury culminating in the development of primary liver tumors. Importantly, this methyl-deficient model of endogenous hepatocarcinogenesis is one of the most relevant models of human liver carcinogenesis that allows studying liver cancer pathogenesis by substantially complementing many shortcomings of humans-only studies. In this review, we describe molecular changes and their role in pathogenesis of liver carcinogenesis induced by methyl deficiency. PMID- 22095782 TI - Design and characterization of a dynamic vibrational culture system. AB - To engineer a functional vocal fold tissue, the mechanical environment of the native tissue needs to be emulated in vitro. We have created a dynamic culture system capable of generating vibratory stimulations at human phonation frequencies. The novel device is composed of a function generator, a power amplifier, an enclosed loudspeaker and a circumferentially-anchored silicone membrane. The vibration signals are translated to the membrane aerodynamically by the oscillating air pressure underneath. The vibration profiles detected on the membrane were symmetrical relative to the centre of the membrane as well as the resting position over the range of frequencies (60-300 Hz) and amplitudes tested (1-30 um). The oscillatory motion of the membrane gave rise to two orthogonal, in plane strain components that are similar in magnitude (0.47%) and are strong functions of membrane thickness. Neonatal foreskin fibroblasts (NFFs) attached to the membrane were subjected to a 1 h vibration at 60, 110 and 300 Hz, with the displacement at the centre of the membrane varying in the range 1-30 um, followed by a 6 h rest. These regimens did not cause morphological changes to the cells. An increase in cell proliferation was detected when NFFs were driven into oscillation at 110 Hz with a normal displacement of 30 um. qPCR results showed that the expression of genes encoding some extracellular matrix proteins was altered in response to changes in vibratory frequency and amplitude. The dynamic culture device provides a potentially useful in vitro platform for evaluating cellular responses to vibration. PMID- 22095783 TI - Cryo-electron microscopy of ribosomal complexes in cotranslational folding, targeting, and translocation. AB - Single-particle cryo-electron microscopy (cryo-EM) became a well-established method to study the structure and function of large macromolecular assemblies in a close to physiological environment. Cryo-EM reconstructions of ribosomal complexes trapped at different stages during translation, cotranslational targeting, and translocation provide new insights on a molecular level into these processes, which are vital for the correct localization and folding of all proteins in the cell. The EM structures in combination with biochemical experiments and available high-resolution crystal or nuclear magnetic resonance (NMR) structures of individual factors and of the ribosome allow for interpretation in quasi-atomic detail of the molecular mechanism of ribosomal complexes, their conformational changes and dynamic interactions with factors like the signal recognition particle, SRP receptor, the translocon, and the chaperone trigger factor. The snapshots obtained by single-particle EM reconstructions enable us to follow the path of a nascent protein from the peptidyl-transferase center, through the ribosomal tunnel, to and across the translocon in the membrane. With new developments in image processing techniques it is possible to sort a biological homogenous sample into different conformational states and to reach subnanometer resolution such that folding of the nascent chain into secondary structure elements can be directly visualized. With improved cryo-electron tomography and correlative light microscopy and EM, it will be possible to visualize ribosomal complexes in their cellular context. PMID- 22095784 TI - Continuous flow system with a polymer-supported dirhodium(II) catalyst: application to enantioselective carbonyl ylide cycloaddition reactions. PMID- 22095785 TI - Functional polyolefins: poly(ethylene)-graft-poly(tert-butyl acrylate) via atom transfer radical polymerization from a polybrominated alkane. AB - Poly(cis-cyclooctene) is synthesized via ring-opening metathesis polymerization in the presence of a chain-transfer agent and quantitatively hydrobrominated. Subsequent graft polymerization of tert-butyl acrylate (tBA) via Cu-catalyzed atom transfer radical polymerization (ATRP) from the non-activated secondary alkyl bromide moieties finally results in PE-g-PtBA copolymer brushes. By varying the reaction conditions, a series of well-defined graft copolymers with different graft densities and graft lengths are prepared. The maximum extent of grafting in terms of bromoalkyl groups involved is approximately 80 mol%. DSC measurements on the obtained graft copolymers reveal a decrease in T(m) with increasing grafting density. PMID- 22095786 TI - African American men significantly underestimate their risk of having prostate cancer at the time of biopsy. AB - BACKGROUND: Guidelines for prostate cancer (PCa) screening recommend physicians to have an informational discussion with patients. At the time of biopsy, patients should be informed of their heightened PCa risk, particularly African Americans (AA) who have significantly higher diagnostic and mortality risk. We tested predictors of patients' estimation of their likelihood of having PCa at the time of biopsy. METHODS: A convenience sample of AA (n = 207) and white (n = 271) biopsy patients was surveyed at the time of prostate biopsy. Participants gave likelihood estimations of having PCa and data on their socio-demographics, health, clinical status, and general and PCa-specific anxiety. Binary logistic regressions tested for predictors of the patients' estimations and biopsy results. RESULTS: Fifty-one percent of AA men answered that they had a '0%' likelihood of having PCa versus 19% of whites, whereas 57% of AA men had abnormal biopsies compared with 42% of whites. In logistic regressions, predictors of patient answers of 0% chance of PCa were AA ethnicity (OR = 4.50; p < 0.001), lower cancer-specific anxiety (OR = 0.93; p < 0.01), less education (OR = 2.38; p < 0.05), and less urinary disturbance (OR = 0.70; p < .05). In a second regression, AA patients trended towards higher positive biopsy rates (OR = 1.43; p = 0.17). CONCLUSIONS: At biopsy, AA more often estimated their likelihood of PCa as 0%, despite higher risks. Reasons for these low estimates and their potential contribution to poor treatment outcomes of AA patients require further investigation. PMID- 22095787 TI - P2Y6 receptor contributes to neutrophil recruitment to inflamed intestinal mucosa by increasing CXC chemokine ligand 8 expression in an AP-1-dependent manner in epithelial cells. AB - BACKGROUND: Inflammatory bowel diseases are characterized by the presence of CXCL8 at the site of lesions resulting in neutrophil recruitment and loss of tissue functions. We report that P2Y(6) receptor activation stimulates CXCL8 expression and release by intestinal epithelial cells (IECs). In this context, we investigated if uridine 5'-diphosphate (UDP) enemas stimulate neutrophil recruitment to the mucosa of mice suffering from colitis-like disease and we characterized the signaling events linking P2Y(6) to CXCL8 expression in IEC. METHODS: Neutrophil recruitment was monitored by immunofluorescence and FACS analysis. Expression of Cxcl1, a mouse functional homolog of CXCL8, was determined by quantitative real-time polymerase chain reaction (qPCR). Pharmacological inhibitors and interfering RNAs were used to characterize the signaling pathway. The outcomes of these treatments on protein phosphorylation and on CXCL8 expression were characterized by western blots, qPCR, luciferase, and chromatin immunoprecipitation (ChIP) assays. RESULTS: Mutation of the AP-1 site in the CXCL8 core promoter abolished the UDP-stimulating effect. The c-fos/c jun dimer was identified as the AP-1 complex regulating CXCL8 in response to UDP stimulation. Regulation of CXCL8 expression by P2Y(6) required PKCdelta activation upstream of the signaling pathway composed of MEK1/2-ERK1/2 and c-fos. UDP administration to mice suffering from colitis-like disease increased the number of neutrophil infiltrating the mucosa, correlating with Cxcl1 increased expression in IEC and the severity of inflammation. CONCLUSIONS: This study not only describes the P2Y(6) signaling mechanism regulating CXCL8 expression in IEC, but it also illustrates the potential of targeting P2Y(6) to reduce intestinal inflammation. PMID- 22095788 TI - Human testis-derived embryonic stem cell-like cells are not pluripotent, but possess potential of mesenchymal progenitors. AB - BACKGROUND: Spontaneous in vitro transition of undifferentiated spermatogonia into the pluripotent cell state has been achieved using neonatal and adult mouse testis tissue. In an effort to establish an analogous source of human patient specific pluripotent stem cells, several research groups have described the derivation of embryonic stem cell-like cells from primary cultures of human testis. These cells are characterized in all studies as growing in compact colonies, expressing pluripotency-associated markers and possessing multilineage differentiation capabilities in vitro, but only one study claimed their ability to induce teratomas. This controversy initiated a debate about the pluripotent state and origin of human testis-derived ES-like cells (htES-like cells). METHODS: htES-like cell colonies were obtained from primary testicular cultures of three individuals and selectively expanded using culture conditions known to support the propagation of blastocyst-derived human embryonic stem cells (ESCs), mouse epiblast stem cells and 'naive' human ESCs. The stem cell properties of htES-like cells were subsequently assessed by testing the expression of ESC specific markers, differentiation abilities in vitro and in vivo, and microarray profiling. RESULTS: The expression of pluripotency-associated markers in htES like cells and their differentiation abilities differed significantly from those of ESCs. Gene expression microarray analysis revealed that htES-like cells possess a transcriptome distinct from human ESCs and fibroblasts, but closely resembling the transcriptome of mesenchymal stem cells (MSCs). The similarity to MSCs was confirmed by detection of SSEA4/CD146 expressing cells within htES-like colonies and efficient in vitro differentiation toward three mesodermal lineages (adipogenic, osteogenic, chondrogenic). CONCLUSIONS: Taken together, these results indicate that htES-like cells, in contrast to pluripotent stem cells derived from adult mouse testis, are not pluripotent and most likely not of germ cell but of mesenchymal origin. PMID- 22095790 TI - Delaying mandatory folic acid fortification policy perpetuates health inequalities: results from a retrospective study of postpartum New Zealand women. AB - BACKGROUND: Internationally, poor periconceptional folic acid uptake has been associated with lower socioeconomic status, minority ethnicity status and unintentional pregnancy. The aim of this study was to describe the extent to which a proposed bread fortification mandate would modify these associations. METHODS: A retrospective survey of postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire. Details on supplement use and bread intake in the periconceptional period, and maternal socio-demographic and obstetric characteristics were obtained. Criteria for the adequate intake of folic acid through proposed mandatory fortification were the habitual consumption of three or more slices of bread/day (118-150 MUg folic acid/day) in the month prior to conception, and during the first trimester of pregnancy. RESULTS: Of the 968 women approached, 758 (78%) agreed to participate. Thirty-three percent of women reported having used folic acid supplements as recommended during the periconceptional period. The proportion of women who would have achieved adequate folic acid intake increased to 59% with mandatory fortification. Socio-demographic predictors of poor folic acid intake from supplements, including younger maternal age, increasing parity, minority ethnicity status, lower education and less income, were rendered either non significant or appreciably attenuated when mandatory fortification was modelled. Notably, the fully adjusted odds ratio for pregnancy planning was reduced from 17.24 [95% confidence interval (CI): 8.13-36.55] to 2.61 (95% CI: 1.73-3.93; both P< 0.001). CONCLUSIONS: Few women comply with periconceptional folic acid recommendations and thus the maximal prevention of neural tube defects is still far from being attained. Data from this retrospective study demonstrate that mandatory fortification benefits segments of the population less likely to use supplements. This finding has compelling policy implications in countries yet to mandate the folic acid fortification of a staple food. PMID- 22095789 TI - A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCzeta) leads to male infertility. AB - BACKGROUND: Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLCzeta). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLCzeta(H398P)), leading to abnormal PLCzeta function and infertility. METHODS AND RESULTS: Here, using a combination of direct-sequencing and mini-sequencing of the PLCzeta gene from the patient and his family, we report the identification of a second PLCzeta mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLCzeta(H233L)), which is predicted to disrupt local protein interactions in a manner similar to PLCzeta(H398P) and was shown to exhibit abnormal calcium oscillatory ability following predictive 3D modelling and cRNA injection in mouse oocytes respectively. We show that PLCzeta(H233L) and PLCzeta(H398P) exist on distinct parental chromosomes, the former inherited from the patient's mother and the latter from his father. Neither mutation was detected utilizing custom-made single-nucleotide polymorphism assays in 100 fertile males and females, or 8 infertile males with characterized oocyte activation deficiency. CONCLUSIONS: Collectively, our findings provide further evidence regarding the importance of PLCzeta at oocyte activation and forms of male infertility where this is deficient. Additionally, we show that the inheritance patterns underlying male infertility are more complex than previously thought and may involve maternal mechanisms. PMID- 22095791 TI - Cold-shock domain family member YB-1 expression in endometrium and endometriosis. AB - BACKGROUND: The Y-box-binding protein (YB-1) is described as a potential oncogene highly expressed in tumors and associated with increased cell survival, proliferation, migration and anti-apoptotic signaling. The aim of our study was to examine the expression and role of YB-1 in human endometriosis (Eo) and its association with cell survival, proliferation and invasion. METHODS: We analyzed the gene and protein expression levels of YB-1 by quantitative real-time RT-PCR and immunoassays, respectively, in peritoneal macrophages, ovarian endometrioma and eutopic endometrial tissues/cells derived from women with (n= 120) and without (n= 91) Eo. We also evaluated the functional consequences of YB-1 knockdown in the Z12 Eo cell line by measuring cell proliferation [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid cell proliferation assay], invasion (Matrigel invasion assay) and spontaneous and tumour necrosis factor (TNFalpha)-induced RANTES (regulated upon activation, normal T-cell expressed and secreted chemokine) expression and apoptosis (ELISA-based assay). RESULTS: YB-1 gene and protein expression was statistically significantly higher in ovarian lesions, eutopic endometrium and peritoneal macrophages of patients with Eo in comparison with the control group. Interestingly, the strongest YB-1 expression was observed in the epithelial compartment of endometrial tissues. In the Z12 cell line, YB-1 knockdown resulted in significant cell growth inhibitory effects including reduced cell proliferation and increased rates of spontaneous and TNFalpha-induced apoptosis. Significantly, higher RANTES expression and decreased cell invasion in vitro were also associated with YB-1 inactivation. CONCLUSION: High YB-1 expression could have an impact on the development and progression of Eo. This study suggests the role of YB-1 as a potential therapeutic target for Eo patients. PMID- 22095792 TI - The effect of recombinant LH on embryo quality: a randomized controlled trial in women with poor ovarian reserve. AB - BACKGROUND: Poor ovarian response is a common clinical problem, affecting up to 26% of IVF cycles. For these women, addition of recombinant luteinizing hormone (rLH) to ovarian hyperstimulation with recombinant FSH has a beneficial effect on ongoing pregnancy rates, but its effect on the yield of top-quality embryos is unknown. METHODS: We conducted a randomized controlled trial in women expected to respond poorly under ovarian hyperstimulation during their first IVF cycle [all women aged 35-41 and women with FSH > 12 IU/ml and antral follicle count (AFC) <= 5]. Women were randomly allocated to rFSH and rLH (2:1 ratio) or rFSH alone (control group) after down-regulation with a GnRH agonist. The primary outcome was the proportion of top-quality embryos per woman on the day of transfer. Secondary outcomes were the number of stimulation days, the number of follicles >=17 mm, the number of oocytes, the fertilization rate, the number of embryos, the number of women with >=1 top-quality embryo, the biochemical, clinical and ongoing pregnancy rates and the miscarriage rate. RESULTS: There were 116 women allocated to the rLH group and 128 allocated to the control group. The proportion of top-quality embryos per woman was 17% in the rLH group and 11% in the control group [mean difference 0.06; 95% confidence interval (CI) -0.01-0.14]. In the rLH and control groups respectively, 47 (41%) and 41 (32%) women had at least one top quality embryo on the day of transfer (relative risk: 1.3, 95% CI 0.91-1.77). The ongoing pregnancy rate was 13 versus 12% (relative risk: 1.1; 95% CI 0.57-2.16) for the rLH group compared with the control group. CONCLUSIONS: This study found no significant difference in embryo quality after the addition of rLH to rFSH for ovarian stimulation in women with poor ovarian reserve. CLINICAL TRIALS IDENTIFIER: NTR1457. PMID- 22095793 TI - Preliminary findings on the use of metadoxine for the treatment of alcohol dependence and alcoholic liver disease. AB - OBJECTIVE: Metadoxine is approved in Europe for alcohol intoxication and is also indicated for alcoholic liver disease (ALD). This study aims to investigate the use of metadoxine as a potential pharmacotherapy for alcohol dependence (AD). METHODS: This is a retrospective study of 94 outpatients with AD, who received metadoxine for alcohol intoxication and were assessed for alcohol consumption, craving [Visual Analog Scale (VAS)] and liver-related and alcohol-related biomarkers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl-transpeptidase, mean corpuscular volume]. RESULTS: Range of metadoxine dose was 500-2000 mg/day, with a mean dose of 1277(s.d.290) mg/day, and for a period of 2-42 days, with a mean period of 8.9(s.d.7.0) days. Follow-up data were available for 52 patients (55.3%); 35(67.3%) patients were completely abstinent. There was a significant decrease in drinks per week, even after substituting baseline drinking as follow-up data for dropouts (p < 0.001) and examining drinking pre-treatment and post-treatment for those who did not achieve abstinence (p < 0.001). There was a significant decrease in the VAS (p < 0.001) and a significant improvement in the AST/ALT ratio (p = 0.03). DISCUSSION: Despite important limitations, this study represents a further preliminary observation suggesting metadoxine as a novel alcohol pharmacotherapy, including in alcohol-dependent patients with ALD. PMID- 22095794 TI - DOSY-NMR analysis of ring-closing metathesis (RCM) products from beta-lactam precursors. AB - The discrimination between cyclomonomers and various oligomers formed during a ring-closing metathesis (RCM) process is not an easy task. Their (1)H NMR patterns are often very similar, and the use of mass spectrometry techniques is usually recommended. Here, we show that the DOSY-NMR method is a reliable tool to help in the identification of cyclomonomers versus cyclodimers by comparing the translational diffusion coefficient of the compounds issued from RCM reactions with the diffusion coefficient of their respective precursors. PMID- 22095795 TI - Enriched designs for assessing discriminatory performance--analysis of bias and variance. AB - In evaluating discriminatory performance of a new modality in a screening setting, a logistical constraint is that the prevalence of the disease of interest is typically very low. This implies that under a standard study design large numbers of subjects have to be evaluated using the new modality. However, if a predicate modality exists in clinical practice, one can base inclusion into the study of the new modality on the clinical results from the predicate to 'enrich' the population of diseased subjects in the study. If this enrichment is not accounted for when estimating sensitivity, specificity, and area under the ROC curve, these 'naive' estimates may be substantially biased compared with expected performance in the intended use population. We derive expressions for the magnitude of this bias in terms of correlations of modality scores. When such estimates are 'corrected' for the sampling weights using inverse probability weighting, the variances of the estimates of the above quantities are affected. We derive here analytic expressions for these variances. For a fixed number of diseased subjects, differential sampling increases the variance of the (corrected) estimates, all other things being equal. However, differential sampling also increases the number with disease for fixed total study size, which decreases the variance of the sensitivity and area under the ROC curve estimates, all other things being equal. The balance of these two effects determines the gain in efficiency when using enrichment and corrected estimates. These principles are illustrated with a simulation study motivated by the Digital Mammographic Imaging Screening Trial study, a trial of digital versus screen film mammography. PMID- 22095796 TI - Selective host-guest binding of anions without auxiliary hydrogen bonds: entropy as an aid to design. PMID- 22095797 TI - Inhibited phenol ionization in reverse micelles: confinement effect at the nanometer scale. AB - We found that the absorption spectra of 2-acetylphenol (2-HAP), 4-acetylphenol (4 HAP), and p-nitrophenol (p-NPh) in water/sodium 1,4-bis(2 ethylhexyl)sulfosuccinate (AOT)/n-heptane reverse micelles (RMs) at various W(0) (W(0) = [H(2)O]/[surfactant]) values studied changed with time if (-)OH ions were present in the RM water pool. There is an evolution of ionized phenol (phenolate) bands to nonionized phenol absorption bands with time and this process is faster at low W(0) values and with phenols with higher bulk water pK(a) values. That is, in bulk water and at the hydroxide anion concentration used, only phenolate species are observed, whereas in AOT RMs at this fixed hydroxide anion concentration, ionized phenols convert into nonionized phenol species over time. Furthermore, we demonstrate that, independent of the (-)OH concentration used to prepare the AOT RMs, the nonionized phenols are the more stable species in the RM media. We explain our results by considering that strong hydrogen-bonding interactions between phenols and the AOT polar head groups result in the existence of only nonionized phenols at the AOT RM interface. The situation is quite different when the phenols are dissolved in cationic benzyl-n hexadecyldimethylammonium chloride RMs. Therein, only phenolates species are present at the (-)OH concentrations used. The results clearly demonstrate that the classical definition of pH does not apply in a confined environment, such as in the interior of RMs and challenge the general idea that pH can be determined inside RMs. PMID- 22095798 TI - Patterns of radiocarpal joint articular cartilage wear in cadavers. AB - The radiocarpal joint transmits about 80% of the compression forces crossing the wrist. However, primary osteoarthritis of this joint is surprisingly uncommon, suggesting that articular cartilage wear is not sufficient to produce arthritic symptoms. By examining the distal radius, scaphoid, and lunate in aged cadavers, wear patterns were charted and measured, allowing assessment of radiocarpal joint wear and mechanics. Bilateral radiocarpal joints of 16 females and 14 males (age 77.7 +/- 14.4, N = 30) were exposed and measurements of the wear recorded microscopically. Wear locations were mapped, and X-Y loci and wear areas calculated. Gender right and sides compared. Over 95% of distal radius wear showed distinct radial-scaphoid and radial-lunate wear areas. These bilateral areas were in the palmar half of the distal radius. One main central wear area was seen in 95% of the scaphoid, and 97% of the lunate articular surfaces that were examined. Articular wear showed a circular pattern and was minimal in 95.7% of the surfaces, and the lunate showed the largest wear area. Wear patterns in males and females support the literature that for most ADLs the wrist is in slight extension and ulnar deviation. There are gender differences, but wear areas between sides were similar. Female wear indicates their wrist is positioned more often in a more extended and ulnarly deviated position than males. The wear patterns suggest rotational movements of the scaphoid and lunate during wrist motion and that the wrist is most often used in neutral flexion/extension to slight extension. PMID- 22095799 TI - Hepatic ratio of phosphatidylcholine to phosphatidylethanolamine predicts survival after partial hepatectomy in mice. AB - A major predictor of failed liver resection and transplantation is nonalcoholic fatty liver disease (NAFLD). NAFLD is linked to a wide spectrum of diseases including obesity and diabetes that are increasingly prevalent in Western populations. Thus, it is important to develop therapies aimed at improving posthepatectomy outcomes in patients with NAFLD, as well as to improve the evaluation of patients slated for hepatic surgery. Decreased hepatic phosphatidylcholine (PC) content and decreased ratio of hepatic PC to phosphatidylethanolamine (PE) have previously been linked to NAFLD. To determine if decreased hepatic PC/PE could predict survival after hepatectomy, we used mouse models lacking key enzymes in PC biosynthesis, namely, phosphatidylethanolamine N-methyltransferase and hepatic-specific CTP:phosphocholine cytidylyltransferase alpha. These mice were fed a high-fat diet to induce NAFLD. We then performed a 70% partial hepatectomy and monitored postoperative survival. We identified hepatic PC/PE to be inversely correlated with the development of steatosis and inflammation in the progression of NAFLD. Decreased hepatic PC/PE before surgery was also strongly associated with decreased rates of survival after partial hepatectomy. Choline supplementation to the diet increased hepatic PC/PE in Pemt(-/-) mice with NAFLD, decreased inflammation, and increased the survival rate after partial hepatectomy. CONCLUSION: Decreased hepatic PC/PE is a predictor of NAFLD and survival following partial hepatectomy. Choline supplementation may serve as a potential therapy to prevent the progression of NAFLD and to improve postoperative outcome after liver surgery. PMID- 22095800 TI - Clobazam approved for seizure disorder. PMID- 22095801 TI - White House addresses drug shortages. PMID- 22095802 TI - CMS seeks pharmacists' engagement in new care models. PMID- 22095803 TI - Health system's readmission prevention plan relies on pharmacists. PMID- 22095804 TI - Forum discusses biosimilars, better biologicals. PMID- 22095805 TI - Duty hours for pharmacy residents. PMID- 22095806 TI - Enhancing faculty-student communication about residencies. PMID- 22095807 TI - Better letter of intent for pharmacy residency applications. PMID- 22095808 TI - Obtaining early clinical exposure as a pharmacy student. PMID- 22095809 TI - Implementation of a pharmacy-driven program to improve nasal mupirocin use. PMID- 22095810 TI - Assessing students' motivation during advanced pharmacy practice experiences. PMID- 22095811 TI - A major stride in the advancement of emergency medicine pharmacy. PMID- 22095812 TI - Pharmacokinetic considerations in Roux-en-Y gastric bypass patients. AB - PURPOSE: Pharmacokinetic considerations in patients who have undergone Roux-en-Y gastric bypass (RYGB) are explored. SUMMARY: The prevalence of obesity, especially morbid obesity, has dramatically increased in recent years. In response, the number of bariatric surgeries performed has risen sharply, as this surgery is the technique demonstrated as being the most effective for sustained treatment of morbid obesity. RYGB, the most popular technique in the United States, combines the principle of restriction (dramatically decreasing stomach size) with malabsorption (bypassing the entire duodenum). It stands to reason that a decrease in gastric and intestinal absorptive surface area may considerably affect oral bioavailability of some drugs. Drugs that require a more acidic environment for absorption, uncoating, or activation and drugs that rely on intestinal transporters located in the duodenum for proper absorption would be most affected. Practitioners looking for guidance in tailoring pharmacotherapy to the RYGB patient will find little help in the primary literature at this time. Until more pharmacokinetic studies are available, practitioners may apply and log P of individual the principles of pK(a) drugs in the attempt to predict the potential impact of the RYGB on a drug's absorption. Likewise, if a drug relies on certain transporters located with highest frequency in the duodenum, alternative therapies can be selected that do not rely on such transport mechanisms for absorption. CONCLUSION: The pK(a), log P, and intestinal transport mechanisms should be considered when determining which drugs may have altered pharmacokinetics in patients who have undergone RYGB. PMID- 22095813 TI - Combination of ketamine and propofol versus either agent alone for procedural sedation in the emergency department. AB - PURPOSE: The safety of using ketamine-propofol combinations as an alternative to using either agent alone for procedural sedation is discussed. SUMMARY: A total of 10 trials comparing the combination of ketamine and propofol with either agent alone for procedural sedation in the emergency department were examined. The evidence reviewed suggests that combining these agents may help to minimize adverse effects such as hypotension and respiratory depression. Ketamine is not commonly used as a single agent in adults because of the risk for emergence reactions; however, when combined with propofol, no significant increase in this adverse effect was found compared with propofol monotherapy. Administering ketamine and propofol can be accomplished by using a two-syringe technique or combining both medications into a single syringe. When two syringes are used, a ketamine 0.3-0.5-mg/kg i.v. bolus dose is administered, followed by a propofol 0.4-1-mg/kg i.v. bolus dose. Sedation is maintained with intermittent i.v. boluses of propofol 0.1-0.5 mg/kg. A 1:1 ratio of ketamine and propofol can also be combined into a single syringe by using the same concentration (10 mg/mL) and equal volumes of each drug, yielding a final concentration of 5 mg/mL for each component. CONCLUSION: The combined use of ketamine and propofol is a reasonable alternative to propofol alone for procedural sedation in patients at higher risk for respiratory depression or hypotension. Use of the combination requires the development of standardized protocols for drug preparation and dosage to minimize the potential for errors. PMID- 22095815 TI - Professional policy as a catalyst to pharmacy's transformation. PMID- 22095814 TI - Probable acyclovir-induced angioedema in a patient with HIV infection and suspected varicella-zoster virus encephalitis. AB - PURPOSE: A probable acyclovir-associated hypersensitivity reaction resulting in severe facial angioedema and respiratory distress is reported. SUMMARY: A 51-year old woman with human immunodeficiency virus (HIV) infection and end-stage renal disease arrived at the emergency department (ED) with a diffuse rash on the chest and back; she was diagnosed with varicella-zoster virus infection, received one dose of i.v. acyclovir, and was discharged home with a prescription for valacyclovir. After taking one dose of the drug, she became confused and agitated. The next day the patient returned to the ED; she was confused and unresponsive, with signs and symptoms suggesting viral encephalitis. After a workup including lumbar puncture fluid, she was treated empirically with i.v. acyclovir for viral encephalitis. Within one hour of receiving the acyclovir infusion, the patient developed angioedema of the lips, tongue, and periorbital areas requiring intubation and transfer to the intensive care unit. Further acyclovir therapy was withheld, and foscarnet therapy was initiated for the presumptive treatment of viral encephalitis. Over the next few days, the patient's angioedema completely resolved; her mental status gradually improved while she completed a 14-day course of foscarnet therapy. The application of the Naranjo scale indicated a probable adverse reaction to acyclovir, likely mediated by acyclovir-specific immunoglobulin E, highlighting the need to consider alternative antiviral agents without cross-reactivity to acyclovir in patients with confirmed or suspected viral encephalitis. CONCLUSION: A 51-year-old woman with HIV infection developed probable acyclovir-induced angioedema after receiving i.v. acyclovir therapy for suspected viral encephalitis. PMID- 22095816 TI - Physical compatibility of telavancin hydrochloride with select i.v. drugs during simulated Y-site administration. AB - PURPOSE: The physical compatibility of telavancin with select i.v. drugs during simulated Y-site administration was evaluated. METHODS: Telavancin for injection was reconstituted according to manufacturer's recommendations and diluted with 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection to a concentration of 7.5 mg/mL. A Y site was simulated in culture tubes by mixing 5 mL of telavancin solution with 5 mL of a tested drug solution and then switching the order of drug mixing. All mixtures were prepared in duplicate and stored at room temperature. Solutions were inspected for visual, turbidity, and pH changes immediately after preparation and 15, 60, and 120 minutes after preparation. RESULTS: Of the 52 drugs tested, telavancin was physically compatible with 39 drugs in all test solutions. Telavancin was incompatible with amphotericin B deoxycholate, liposomal amphotericin B, digoxin, esomeprazole sodium, furosemide, levofloxacin, and micafungin sodium in all diluents. Colistimethate sodium, cyclosporine, heparin sodium, imipenem cilastatin sodium, methylprednisolone sodium succinate, and propofol were incompatible with telavancin in specific diluents. Incompatibilities included precipitation, positive Tyndall beam test, and increases in turbidity. There were no substantial changes in pH over the 120-minute study period. CONCLUSION: Telavancin 7.5 mg/mL in 0.9% sodium chloride injection, 5% dextrose injection, and lactated Ringer's injection was found to be physically compatible for 120 minutes at room temperature with 39 of the 52 drugs tested during simulated Y site administration. Seven drugs were incompatible in all diluents, and 6 were incompatible in at least one diluent. PMID- 22095817 TI - Evaluating and classifying pharmacists' quality interventions in the emergency department. AB - PURPOSE: The results of an evaluation of the impact of pharmacists' medication related interventions on quality of care in the emergency department (ED) setting are reported. METHODS: Using data from a previously published observational study of medication errors intercepted by ED pharmacists at four academic medical centers, trained reviewers retrospectively analyzed 130 additional pharmacist interventions (those not categorized as medication errors in the primary study) over a specified four-month period to identify "quality interventions" (QIs), defined as those that (1) prevented misuse, underuse, or overuse of medications or (2) improved adherence to quality standards or evidence-based medicine (EBM) standards. The study included an evaluation of the medication classes associated with QIs and the acceptance of pharmacist-recommended QIs. RESULTS: The reviewers identified a total of 91 pharmacist QIs at the four sites during the study period (2.3 QIs per 100 patients or about 1 QI per 100 medication orders). About 45% of the identified QIs improved adherence with EBM or national quality standards; other QIs prevented medication underuse (34%), misuse (14%), or overuse (6%). Pharmacists' QIs most often pertained to antiinfective agents (39%), cardiovascular agents (13%), and anticoagulants and thrombolytics (12%). The overall rate of acceptance of pharmacists' QIs was 93.4%. CONCLUSION: A secondary analysis of data from a previously published study at four medical centers indicated that ED pharmacists often recommend interventions that improve the quality of medication use and adherence to EBM and national quality standards. PMID- 22095818 TI - Clinical and economic analysis of short-course versus standard-course antithymocyte globulin (rabbit) induction therapy in deceased-donor renal transplant recipients. AB - PURPOSE: The immunosuppressive effects of and costs associated with short-course antithymocyte globulin rabbit (ATG [rabbit]) therapy versus standard-course ATG (rabbit) therapy in deceased-donor renal transplant recipients were evaluated. METHODS: The records of 84 consecutive patients who received a deceased-donor renal transplant at the Montefiore Einstein Center for Transplantation in 2008 were retrospectively reviewed. Donor and recipient characteristics, including rates of biopsy-confirmed acute rejection, serum creatinine (SCr) levels, and frequency of complications, and drug costs were collected. Patients were excluded if they had donor-specific antibodies identified before transplantation or hepatitis-C-positive serology or were under 18 years of age. RESULTS: A total of 60 patients were included in the study, with 28 receiving short-course ATG (rabbit) therapy and 32 receiving standard-course ATG (rabbit) therapy. Baseline patient demographic characteristics were similar between groups. Six months after transplantation, biopsy-confirmed acute rejection episodes did not significantly differ between the short-course ATG (rabbit) and standard-course ATG (rabbit) groups (17.8% versus 12.5%, respectively), nor did SCr concentrations (1.56 mg/dL versus 1.85 mg/dL). The frequency of therapy-related leukopenia was greater in patients receiving standard-course ATG (rabbit). Patients treated with short course ATG (rabbit) received a total mean dose of 4.6 mg/kg, compared with 7.3 mg/kg for patients in the standard-course ATG (rabbit) group, resulting in a mean cost saving of $2548 per patient. CONCLUSION: After six months, there were no significant differences in biopsy- confirmed acute rejection episodes or SCr levels between deceased-donor renal transplant recipients receiving short-course versus standard-course ATG (rabbit) induction therapy. The mean cost saving associated with short-course therapy was $2548 per patient. PMID- 22095819 TI - An advanced teaching certificate program for postgraduate year 2 residents. AB - PURPOSE: The rationale, structure, and elements of a teaching certificate program for second-year pharmacy residents are described. SUMMARY: Evidence suggests that postgraduate year 2 (PGY2) pharmacy residents generally have limited options for the continued development of their teaching skills after the completion of a postgraduate year 1 (PGY1) teaching certificate program. To expand those options, the University of Oklahoma College of Pharmacy developed a program (implemented during the 2005-06 residency year and formalized during the 2010-11 residency year) of advanced teaching-skills development that allows PGY2 residents to build on the foundational skills acquired in its PGY1 teaching certificate program; the new program also has been adapted to meet the needs of incoming PGY2 residents who earned PGY1-level teaching certificates at other institutions. The teaching certificate program comprises eight modules of instruction in advanced topic areas (e.g., course coordination, grading, active learning, teaching with technology) designed to prepare PGY2 residents for future faculty and preceptor positions. Among other required and optional activities, residents in the PGY2 certificate program receive hands-on instruction in course-coordination duties through a shadowing experience, serve as preceptors to fourth-year pharmacy students under the guidance of the residency director, and redeliver refined versions of lectures originally presented as PGY1 residents. CONCLUSION: A teaching certificate program specifically designed for PGY2 residents has allowed participants to continue to develop and refine their teaching skills through learning activities beyond those provided in the PGY1 program. PMID- 22095820 TI - Implementing an electronic medical record with computerized prescriber order entry at a critical access hospital. PMID- 22095821 TI - ASHP guidelines on emergency medicine pharmacist services. PMID- 22095822 TI - Mrp2 is involved in the efflux and disposition of fosinopril. AB - The multidrug-resistance-associated proteins 1 and 2 (MRP1/MRP2) are transporters responsible for the efflux of drugs and endogenous compounds. Madin Darby canine kidney (MDCK) cells transfected with the human MRP1 or MRP2 genes were used to assess whether several widely used pharmaceuticals are potential substrates by examining their differential toxicity, accumulation and efflux. Loratadine, an antihistamine, was 1.4-fold less toxic to MRP1 cells and its retention was 1.3 fold lower than that from MDCK control cells. Fosinopril, an angiotensin converting enzyme inhibitor, was 2.4-fold less toxic and its retention was 4.5 fold lower in MRP2-transfected cells compared with control cells. To determine whether fosinopril contributed to a drug-drug interaction, fosinopril efflux was examined in vitro in combination with other known or suspected MRP2 substrates over a period of 20 min. When fosinopril was coincubated with desloratadine, loratadine or methotrexate, its retention was increased by 2-, 4.7- and 2-fold, respectively, which likely indicates that a drug-drug interaction is occurring. In vivo studies were conducted, in which FVB wild-type and FVB/Mrp2(-/-) mice were dosed with fosinopril and the known MRP2 substrate methotrexate, and tissues collected after 1 h. In mice lacking Mrp2, drug levels were reduced in the intestine by 1.5-fold, but increased in the liver, serum and kidneys, by 2.1-, 2.9- and 3-fold, respectively. These data suggest that, in the absence of Mrp2, fosinopril alters the retention of a second drug. These findings will help increase our understanding of the role that MRP2 plays in altering the retention and disposition of coadministered pharmaceuticals. PMID- 22095824 TI - Metabolic syndrome: evidences for a personalized nutrition. AB - Both insulin resistance and dyslipidaemia are determined by genetic and environmental factors. Depending on their expression and their function, gene variants may influence either insulin action or other metabolic traits. Nutrition also plays an important role in the development and progression of these conditions. Genetic background may interact with habitual dietary fat composition, affecting predisposition to insulin resistance syndrome and individual responsiveness to changes in dietary fat intake. In this context, nutrigenetics has emerged as a multidisciplinary field focusing on studying the interactions between nutritional and genetic factors and health outcomes. Due to the complex nature of gene-environment interactions, however, dietary therapy may require a "personalized" nutrition approach in the future. Although the results have not always been consistent, gene variants that affect primary insulin action, and particularly their interaction with the environment, are important modulators of glucose metabolism. The purpose of this review is to present some evidence of studies that have already demonstrated the significance of gene nutrient interactions (adiponectin gene, Calpain-10, glucokinase regulatory protein, transcription factor 7-like 2, leptin receptor, scavenger receptor class B type I etc.) that influence insulin resistance in subjects with metabolic syndrome. PMID- 22095823 TI - Genetic variation of pre-mRNA alternative splicing in human populations. AB - The precise splicing outcome of a transcribed gene is controlled by complex interactions between cis regulatory splicing signals and trans-acting regulators. In higher eukaryotes, alternative splicing is a prevalent mechanism for generating transcriptome and proteome diversity. Alternative splicing can modulate gene function, affect organismal phenotype and cause disease. Common genetic variation that affects splicing regulation can lead to differences in alternative splicing between human individuals and consequently impact expression level or protein function. In several well-documented examples, such natural variation of alternative splicing has indeed been shown to influence disease susceptibility and drug response. With new microarray and sequencing-based genomic technologies that can analyze eukaryotic transcriptomes at the exon or nucleotide level, it has become possible to globally compare the alternative splicing profiles across human individuals in any tissue or cell type of interest. Recent large-scale transcriptome studies using high-density splicing sensitive microarray and deep RNA sequencing (RNA-Seq) have revealed widespread genetic variation of alternative splicing in humans. In the future, an extensive catalog of alternative splicing variation in human populations will help elucidate the molecular underpinnings of complex traits and human diseases, and shed light on the mechanisms of splicing regulation in human cells. PMID- 22095825 TI - Reciprocal actions of ATF5 and Shh in proliferation of cerebellar granule neuron progenitor cells. AB - Precise regulation of neuroprogenitor cell proliferation and differentiation is required for successful brain development, but the factors that contribute to this are only incompletely understood. The transcription factor ATF5 promotes proliferation of cerebral cortical neuroprogenitor cells and its down regulation permits their differentiation. Here, we examine the expression and regulation of ATF5 in cerebellar granule neuron progenitor cells (CGNPs) as well as the role of ATF5 in the transition of CGNPs to postmitotic cerebellar granule neurons (GCNs). We find that ATF5 is expressed by proliferating CGNPs in both the embryonic and postnatal cerebellar external granule layer (EGL) and in the rhombic lip, the embryonic structure from which the EGL arises. In contrast, ATF5 is undetectable in postmitotic GCNs. In highly enriched dissociated cultures of CGNPs and CGNs, ATF5 is expressed only in CGNPs. Constitutive ATF5 expression in CGNPs does not affect their proliferation or exit from the cell cycle. In contrast, in presence of sonic hedgehog (Shh), a mitogen for CGNPs, constitutively expressed ATF5 promotes CGNP proliferation and delays their cell cycle exit and differentiation. Conversely, ATF5 loss-of-function conferred by a dominant-negative form of ATF5 significantly diminishes Shh-stimulated CGNP proliferation and promotes differentiation. In parallel with its stimulation of CGNP proliferation, Shh enhances ATF5 expression by what appeared to be a posttranscriptional mechanism involving protein stabilization. These findings indicate a reciprocal interaction between ATF5 and Shh in which Shh stimulates ATF5 expression and in which ATF5 contributes to Shh-stimulated CGNP expansion. PMID- 22095826 TI - Status of cardiovascular health in US adults: prevalence estimates from the National Health and Nutrition Examination Surveys (NHANES) 2003-2008. AB - BACKGROUND: The American Heart Association's 2020 Strategic Impact Goals define a new concept, cardiovascular (CV) health; however, current prevalence estimates of the status of CV health in US adults according to age, sex, and race/ethnicity have not been published. METHODS AND RESULTS: We included 14 515 adults (>=20 years of age) from the 2003 to 2008 National Health and Nutrition Examination Surveys. Participants were stratified by young (20-39 years), middle (40-64 years), and older (>=65 years) ages. CV health behaviors (diet, physical activity, body mass index, smoking) and CV health factors (blood pressure, total cholesterol, fasting blood glucose, smoking) were defined as poor, intermediate, or ideal. Fewer than 1% of adults exhibited ideal CV health for all 7 metrics. For CV health behaviors, nonsmoking was most prevalent (range, 60.2%-90.4%), whereas ideal Healthy Diet Score was least prevalent (range, 0.2%-2.6%) across groups. Prevalences of ideal body mass index (range, 36.5%-45.3%) and ideal physical activity levels (range, 50.2%-58.8%) were higher in young adults compared with middle or older ages. Ideal total cholesterol (range, 23.7%-36.2%), blood pressure (range, 11.9%-16.3%), and fasting blood glucose (range, 31.2% 42.9%) were lower in older adults compared with young and middle-aged adults. Prevalence of poor CV health factors was lowest in young age but higher at middle and older ages. Prevalence estimates by age and sex were consistent across race/ethnic groups. CONCLUSIONS: These prevalence estimates of CV health represent a starting point from which effectiveness of efforts to promote CV health and prevent CV disease can be monitored and compared in US adult populations. PMID- 22095827 TI - Niacin inhibits vascular inflammation via the induction of heme oxygenase-1. AB - BACKGROUND: Heme oxygenase-1 (HO-1) is a cytoprotective protein whose expression is consistently associated with therapeutic benefits in a number of pathological conditions such as atherosclerotic vascular disease and inflammation. Niacin is a pleiotropic drug that slows the progression of coronary artery disease and increases serum levels of the HO-1 enzymatic product bilirubin. This study asks if the cardioprotective properties of niacin involve the induction of HO-1. METHODS AND RESULTS: New Zealand White rabbits received chow or chow supplemented with 0.6% (wt/wt) niacin for 2 weeks. Acute vascular inflammation was induced in the animals by placing a nonocclusive silastic collar around the left common carotid artery. At 24 hours after collar implantation, serum bilirubin and vascular, liver, and spleen HO-1 messenger RNA levels were significantly increased. Vascular inflammation was decreased in the niacin-supplemented animals compared with control. Treatment of the animals with tin protoporphyrin-IX, a global HO inhibitor, or HO-1 small interfering RNA to knock down carotid artery HO-1 attenuated the ability of niacin to inhibit vascular inflammation. Treatment of cultured human coronary artery endothelial cells with niacin increased HO-1 expression by activating the nuclear factor-E2-related factor 2/p38 mitogen activated protein kinase signaling pathway and inhibiting tumor necrosis factor alpha-induced endothelial inflammation. The antiinflammatory effects of niacin in human coronary artery endothelial cells were mimicked by bilirubin and abolished by incubation with tin protoporphyrin-IX and knock down of nuclear factor-E2 related factor 2. CONCLUSIONS: Niacin activates HO-1 in vivo and in vitro. Induction of HO-1 may be partly responsible for the vascular protective properties of niacin. PMID- 22095828 TI - Physician procedure volume and complications of cardioverter-defibrillator implantation. AB - BACKGROUND: The outcomes of procedures are often better when they are performed by more experienced physicians. We assessed whether the rate of complications after implantable cardioverter-defibrillator (ICD) placement varied with the volume of procedures a physician performed. METHODS AND RESULTS: We studied 356 515 initial ICD implantations in the National Cardiovascular Data Registry-ICD Registry, performed by 4011 physicians in 1463 hospitals. We examined the relationship between physician annual ICD implantation volume and in-hospital complications, using hierarchical logistic regression to adjust for patient characteristics, implanting physician certification, hospital characteristics, hospital annual procedure volume, and the clustering of patients within hospitals and by physician. We repeated this analysis for ICD subtypes: single chamber, dual chamber, and biventricular. There were 10 994 patients (3.1%) with a complication after ICD implantation, and 1375 died (0.39%). The complication rate decreased with increasing physician procedure volume from 4.6% in the lowest quartile to 2.9% in the highest quartile (P<0.0001), and the mortality rate decreased from 0.72% to 0.36% (P<0.0001). The inverse relationship between physician procedure volume and complications remained significant after adjusting for patient, physician, and hospital characteristics (OR 1.55 for complications in lowest-volume quartile compared with highest; 95% confidence interval, 1.34 1.79; P<0.0001). This inverse relationship was independent of physician specialty and of hospital volume, was consistent across ICD subtypes, and was also evident for in-hospital mortality. CONCLUSION: Physicians who implant more ICDs have lower rates of procedural complications and in-hospital mortality, independent of hospital procedure volume, physician specialty, and ICD type. PMID- 22095829 TI - Multipotent vasculogenic pericytes from human pluripotent stem cells promote recovery of murine ischemic limb. AB - BACKGROUND: Pericytes represent a unique subtype of microvessel-residing perivascular cells with diverse angiogenic functions and multilineage developmental features of mesenchymal stem cells. Although various protocols for derivation of endothelial and/or smooth muscle cells from human pluripotent stem cells (hPSC, either embryonic or induced) have been described, the emergence of pericytes in the course of hPSC maturation has not yet been elucidated. METHODS AND RESULTS: We found that during hPSC development, spontaneously differentiating embryoid bodies give rise to CD105(+)CD90(+)CD73(+)CD31(-) multipotent clonogenic mesodermal precursors, which can be isolated and efficiently expanded. Isolated and propagated cells expressed characteristic pericytic markers, including CD146, NG2, and platelet-derived growth factor receptor beta, but not the smooth muscle cell marker alpha-smooth muscle actin. Coimplantation of hPSC-derived endothelial cells with pericytes resulted in functional and rapid anastomosis to the murine vasculature. Administration of pericytes into immunodeficient mice with limb ischemia promoted significant vascular and muscle regeneration. At day 21 after transplantation, recruited hPSC pericytes were found incorporated into recovered muscle and vasculature. CONCLUSIONS: Derivation of vasculogenic and multipotent pericytes from hPSC can be used for the development of vasculogenic models using multiple vasculogenic cell types for basic research and drug screening and can contribute to angiogenic regenerative medicine. PMID- 22095830 TI - Are mural cells guardians of stemness?: From pluri- to multipotency via vascular pericytes. PMID- 22095831 TI - DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity. AB - Patients and models of cystic fibrosis (CF) exhibit consistent abnormalities of polyunsaturated fatty acid composition, including decreased linoleate (LA) and docosahexaenoate (DHA) and variably increased arachidonate (AA), related in part to increased expression and activity of fatty acid desaturases. These abnormalities and the consequent CF-related pathologic manifestations can be reversed in CF mouse models by dietary supplementation with DHA. However, the mechanism is unknown. This study investigates this mechanism by measuring the effect of exogenous DHA and eicosapentaenoate (EPA) supplementation on fatty acid composition and metabolism, as well as on metabolic enzyme expression, in a cell culture model of CF. We found that both DHA and EPA suppress the expression and activity of Delta5- and Delta6-desaturases, leading to decreased flux through the n-3 and n-6 PUFA metabolic pathways and decreased production of AA. The findings also uncover other metabolic abnormalities, including increased fatty acid uptake and markedly increased retroconversion of DHA to EPA, in CF cells. These results indicate that the fatty acid abnormalities of CF are related to intrinsic alterations of PUFA metabolism and that they may be reversed by supplementation with DHA and EPA. PMID- 22095833 TI - Critical evaluation of the microwave effect on radical (co)polymerizations. AB - Critical evaluations of the microwave effect on initiation, propagation, and termination during conventional radical polymerizations (RPs) of methyl methacrylate (MMA) and random copolymerization of styrene (St) with (meth)acrylates are examined by comparing microwave heating (MWH) and conventional heating (CH). Poly(methyl methacrylate) with similar $ ?overline M_{?rm n} $, $ ?overline M_{?rm w} $/$ ?overline M_{?rm n} $, and conversion are obtained under precisely controlled temperature, indicating very small changes of propagation rate constant. Rate enhancement in the absence of precise temperature control is mostly due to the higher reaction temperature of the reaction mixture than the apparent value indicated on display. Rates of initiator decomposition under well-controlled temperature are essentially the same for MWH and CH. PMID- 22095832 TI - Primary fatty acid amide metabolism: conversion of fatty acids and an ethanolamine in N18TG2 and SCP cells. AB - Primary fatty acid amides (PFAM) are important signaling molecules in the mammalian nervous system, binding to many drug receptors and demonstrating control over sleep, locomotion, angiogenesis, and many other processes. Oleamide is the best-studied of the primary fatty acid amides, whereas the other known PFAMs are significantly less studied. Herein, quantitative assays were used to examine the endogenous amounts of a panel of PFAMs, as well as the amounts produced after incubation of mouse neuroblastoma N(18)TG(2) and sheep choroid plexus (SCP) cells with the corresponding fatty acids or N tridecanoylethanolamine. Although five endogenous primary amides were discovered in the N(18)TG(2) and SCP cells, a different pattern of relative amounts were found between the two cell lines. Higher amounts of primary amides were found in SCP cells, and the conversion of N-tridecanoylethanolamine to tridecanamide was observed in the two cell lines. The data reported here show that the N(18)TG(2) and SCP cells are excellent model systems for the study of PFAM metabolism. Furthermore, the data support a role for the N-acylethanolamines as precursors for the PFAMs and provide valuable new kinetic results useful in modeling the metabolic flux through the pathways for PFAM biosynthesis and degradation. PMID- 22095834 TI - Palladium-catalyzed allylic sulfinylation and the Mislow-Braverman-Evans rearrangement. PMID- 22095835 TI - Sensitivity improvement of 1H-15N cross-polarization at high MAS frequency applied to NMR structural characterization of organic solids. AB - (15)N CP/MAS solid state NMR should be a method of choice to obtain essential structural information on organic materials containing nitrogen atoms. However, the technique is generally not selected for the characterization of non-labelled chemical compounds, which represents the most common situation encountered by chemists. Actually, due to the poor sensitivity of (15)N the method is time consuming and a very fine calibration is often a prerequisite to reach a sufficient signal/noise. The main drawback comes from the weakness of (15)N-(1)H dipolar couplings which leads to a splitting of the static Hartman Hahn condition into very narrow sideband conditions under MAS. Practically, it is more difficult to obtain a high enough CP transfer level on (15)N for the entire spectrum than on other more conventional nuclei like (13)C. An experimental investigation of the CP efficiency using the ramp and adiabatic CP transfer experiments is here proposed. Preliminary adjustments of experimental settings were first made on an (15)N-labeled substituted heterocyclic model system, and then applied to several other organic compounds. Particular attention was paid to the detection of non protonated nitrogen atoms with a significant chemical shift anisotropy, which represented the least favourable case. It was experimentally demonstrated that, for these atoms, the adiabatic passage provided a much higher transfer level than the more conventional ramp sequence leading to an enhancement factor of up to 3.5 at a MAS frequency of 30 kHz. The resulting sensitivity rendered possible the detection of non-protonated nitrogen atoms at natural abundance with 2.5-mm rotors at 9.4 T. PMID- 22095836 TI - The effect of multivitamin supplementation on mood and stress in healthy older men. AB - OBJECTIVE: There is a demonstrated association between poor mood and deficiency in several micronutrients. Multivitamin supplements contain a wide range of nutrients, suggesting that they may be effective in improving mood; however, few studies have investigated this potential in randomized, controlled trials. This study investigates the effects of a multivitamin, mineral, and herbal supplement on mood and stress in a group of healthy, older male volunteers. METHODS: In this randomized, double-blind, placebo-controlled trial, fifty men, aged 50-69 years, supplemented for a period of 8 weeks with a multivitamin formulation that contained vitamins (at levels above recommended daily intakes), minerals, antioxidants, and herbal extracts, or a placebo. They completed a series of mood and stress questionnaires at baseline and post-supplementation. RESULTS: Compared with placebo, there was a significant reduction in the overall score on a depression anxiety and stress scale and an improvement in alertness and general daily functioning in the multivitamin group. CONCLUSIONS: Supplementation with a multivitamin, mineral and herbal formulation may be useful in improving alertness and reducing negative mood symptoms and may also improve feelings of general day to-day well-being. PMID- 22095837 TI - Enrolling in deep brain stimulation research for depression: influences on potential subjects' decision making. AB - BACKGROUND: Ethical concerns regarding early-phase clinical trials of DBS for treatment-resistant depression (TRD) include the possibility that participants' decisions to enroll might be motivated by unrealistic expectations of personal benefit or minimization of risks. METHODS: Thematic analyses were conducted on a sample of 26 adults considering participation in two DBS trials. Influences on the decision making of these potential DBS trial participants were derived from responses to questions posed in the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), a semi-structured interview designed to evaluate decisional capacity to consent to research. RESULTS: Participants cited numerous factors as influential in their enrollment decisions, including perceived lack of other treatment options, desire to take initiative, beliefs about DBS as a novel treatment, possibility of DBS efficacy, hoped-for improvements, potential risks and disadvantages of DBS or clinical trial participation, and altruism. No individual expressed a set of motivations or influencing factors that suggested compromised decision-making capacity or diminished voluntariness of decision making. CONCLUSIONS: These results suggest that individuals make the decision to enroll in early-phase trials of DBS for TRD based on a number of complex and sometimes idiosyncratic considerations, and that the trials that were studied utilized sufficiently robust informed consent processes. These findings offer evidence that the emerging research area of DBS can be advanced in an ethically sound manner, provided that safeguards and processes for discussing trials with participants are carefully and proactively enacted. PMID- 22095838 TI - Laparoscopic myomectomy focusing on the myoma pseudocapsule: technical and outcome reports. AB - BACKGROUND: Our aim was to assess surgical complaints and reproductive outcomes of laparoscopic intracapsular myomectomies by a prospective observational study run in University affiliated hospitals. METHODS: Between 2005 and 2010, 235 women underwent subserous and intramural laparoscopic myomectomy of fibroids (4-10 cm in diameter) for indications of pelvic pain, menstrual disorders, a large growing myoma or infertility. The main outcome measures were post-surgical parameters, including complications, the need for subsequent surgery or symptomatic relief, resumption of normal life and reproductive outcome. RESULTS: Pelvic pain occurred in 27%, menorrhagia or metorrhagia in 21%, a large growing myoma in 10% and infertility in 42% of women. Single fibroids occurred in 51.9% of patients while 48.1% had multiple myomas. Of all patients, 58.2% had subserosal and 41.8% had intramural myomas. No laparoscopies were converted to laparotomy. In 3 years, 1.2% of patients had a second laparoscopic myomectomy for recurrent fibroids. The mean total operative laparoscopic time was 84 min (range 25-126 min), with mean blood loss of 118 +/- 27.9 ml. By 48 h after surgery, 86.3% were discharged with no major post-operative complications. No late complications, such as bleeding, urinary tract infections or bowel lesions, occurred. Of the women who underwent myomectomy for infertility, 74% finally conceived. At term, 32.9% of patients underwent Caesarean section, 24.8% delivered by vacuum extractor and 42.2% had spontaneous deliveries. No case of uterine rupture occurred. CONCLUSIONS: Intracapsular subserous and intramural myomectomy saving the fibroid pseudocapsule showed few early and no late surgical complications, enhanced healing by preserving myometrial integrity and allowed a good fertility rate and delivery outcome. In young patients suffering fibroids, laparoscopic intracapsular myomectomy is a potential recommended surgical treatment. PMID- 22095839 TI - Endoscopic anterior cricoid split with balloon dilation in infants with failed extubation. AB - Subglottic injury (SGI) is a known complication of prolonged intubation in neonates and infants and can lead to failed extubation. SGI is a spectrum that includes mucosal edema, ulceration, granulation perichondritis, and mature scar formation. Although medical management aimed at treating mucosal edema and extraesophageal reflux is successful in treating a majority of patients, some require surgical intervention to successfully achieve extubation. The surgical options for these patients include tracheostomy, open anterior cricoid split (ACS), and laryngotracheal reconstruction with cartilage grafting. Open ACS is performed through an external incision requiring placement of a drain for a few days. Extubation success rates in the 70% to 80% range have been widely reported. In this article we describe an endoscopic technique for ACS, in which after an endoscopic airway assessment confirms isolated SGI, the cricoid cartilage is divided transluminally with cold steel. Balloon dilation (BD) is then performed with an appropriately sized angiography balloon. We describe preliminary results in which two of three patients were successfully extubated after endoscopic ACS with BD. We believe that this novel technique is a promising alternative to open ACS with similar indications. In addition to the avoidance of a skin incision, endoscopic ACS with BD may enable extubation with comparably shorter lengths of postprocedure intubation than open ACS. Larger series will be required to further establish outcomes of this procedure, including success and complication rates. PMID- 22095840 TI - Domain-specific folding kinetics of staphylococcal nuclease observed through single-molecule FRET in a microfluidic mixer. PMID- 22095842 TI - A universal representation of the states of chemical matter including metastable configurations in phase diagrams. PMID- 22095843 TI - Effects of dietary exposure of mink (Mustela vison) to 2,3,7,8-tetrachlorodibenzo p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, and 2,3,7,8-tetrachlorodibenzofuran on reproduction and offspring viability and growth. AB - This study assessed the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) on the reproductive performance of female mink (Mustela vison) and the viability and growth of their offspring. Nine adult female mink were randomly assigned to one of 13 dietary treatments (one control and four doses each of TCDD, PeCDF, and TCDF [2.1-8.4, 4.0-15 and 5.2-25 ng TCDD toxic equivalents (TEQ)/kg body wt/d]). Diets were fed from two months prior to breeding through weaning of offspring at six weeks of age. At least nine kits per treatment group were maintained on their diets through 27 weeks of age. There were no effects on litter size or viability of offspring. No consistent effects were observed on body mass or relative organ masses of animals at any age. 2,3,7,8 Tetrachlorodibenzo-p-dioxin and PeCDF accumulated in the liver and adipose tissue, but TCDF cleared rapidly. The lack of significant effects on reproduction and offspring viability contrasts with effects reported for mink exposed to environmentally derived PCB mixtures with equivalent TCDD potencies. This suggests that it may be inappropriate to apply toxicity reference values associated with PCB mixtures to animals also exposed to TCDD, PeCDF, or TCDF, and the World Health Organization TCDD toxic equivalency factors for some congeners may not be appropriate for mink. PMID- 22095841 TI - Endoplasmic reticulum-tethered transcription factor cAMP responsive element binding protein, hepatocyte specific, regulates hepatic lipogenesis, fatty acid oxidation, and lipolysis upon metabolic stress in mice. AB - cAMP responsive element-binding protein, hepatocyte specific (CREBH), is a liver specific transcription factor localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here, we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the liver. Under the normal chow diet, CrebH knockout mice display a modest decrease in hepatic lipid contents, but an increase in plasma triglycerides (TGs). After having been fed an atherogenic high-fat (AHF) diet, massive accumulation of hepatic lipid metabolites and significant increase in plasma TG levels were observed in the CrebH knockout mice. Along with the hypertriglyceridemia phenotype, the CrebH null mice displayed significantly reduced body-weight gain, diminished abdominal fat, and increased nonalcoholic steatohepatitis activities under the AHF diet. Gene-expression analysis and chromatin-immunoprecipitation assay indicated that CREBH is required to activate the expression of the genes encoding functions involved in de novo lipogenesis, TG and cholesterol biosynthesis, FA elongation and oxidation, lipolysis, and lipid transport. Supporting the role of CREBH in lipogenesis and lipolysis, forced expression of an activated form of CREBH protein in the liver significantly increases accumulation of hepatic lipids, but reduces plasma TG levels in mice. CONCLUSION: All together, our study shows that CREBH plays a key role in maintaining lipid homeostasis by regulating the expression of the genes involved in hepatic lipogenesis, FA oxidation, and lipolysis under metabolic stress. The identification of CREBH as a stress-inducible metabolic regulator has important implications in the understanding and treatment of metabolic disease. PMID- 22095844 TI - Quality control in tRNA charging. AB - Faithful translation of the genetic code during protein synthesis is fundamental to the growth, development, and function of living organisms. Aminoacyl-tRNA synthetases (AARSs), which define the genetic code by correctly pairing amino acids with their cognate tRNAs, are responsible for 'quality control' in the flow of information from a gene to a protein. When differences in binding energies of amino acids to an AARS are inadequate, editing is used to achieve high selectivity. Editing occurs at the synthetic active site by hydrolysis of noncognate aminoacyl-adenylates (pretransfer editing) and at a dedicated editing site located in a separate domain by deacylation of mischarged aminoacyl-tRNA (posttransfer editing). Access of nonprotein amino acids, such as homocysteine or ornithine, to the genetic code is prevented by the editing function of AARSs, which functionally partitions amino acids present in living cells into protein and nonprotein amino acids. Continuous editing is part of the tRNA aminoacylation process in living organisms from bacteria to human beings. Preventing mistranslation by the clearance of misactivated amino acids is crucial to cellular homeostasis and has a role in etiology of disease. Although there is a strong selective pressure to minimize mistranslation, some organisms possess error-prone AARSs that cause mistranslation. Elevated levels of mistranslation and the synthesis of statistical proteins can be beneficial for pathogens by increasing phenotypic variation essential for the evasion of host defenses. PMID- 22095845 TI - Synergistic control of mesenchymal stem cell differentiation by nanoscale surface geometry and immobilized growth factors on TiO2 nanotubes. AB - The aim of this study is to elucidate whether combined environmental signals provided by nanoscale topography and by growth factors control cell behavior of mesenchymal stem cells (MSCs) in a synergistic or simply additive manner. Chondrogenic and osteogenic differentiation of MSCs is studied on vertically aligned TiO(2) nanotubes of size 15 and 100 nm with and without immobilized bone morphogenetic protein-2 (BMP-2). Although BMP-2 coating stimulates both chondrogenic and osteogenic differentiation of MSCs, the response strongly depends on the surface nanoscale geometry of the BMP-2-coated nanotubes. Chondrogenic differentiation is strongly supported on 100 nm BMP-2-coated nanotubes, but not on 15 nm nanotubes, which induce spreading and de differentiation of chondrocytes. A similar response is observed with primary chondrocytes, which maintain their chondrogenic phenotype on BMP-2-coated 100 nm nanotubes, but de-differentiate on 15 nm nanotubes. In contrast, osteogenic differentiation is greatly enhanced on 15 nm but not on 100 nm BMP-2-coated nanotubes as shown previously. Furthermore, covalent immobilization of BMP-2 rescues MSCs from apoptosis occurring on uncoated 100 nm TiO(2) nanotube surfaces. Thus, combined signals provided by BMP-2 immobilized to a defined lateral nanoscale spacing geometry seem to contain environmental cues that are able to modulate a lineage-specific decision of MSC differentiation and cell survival in a synergistic manner. PMID- 22095846 TI - Hypothesis: prolactin is tumorigenic to human breast: dispelling the myth that prolactin-induced mammary tumors are rodent-specific. AB - The commonly held assumption that rodent mammary tumors resulting from elevated prolactin are species-specific, or not biologically relevant to humans, is incorrect. Substantial epidemiological, clinical, and biological evidence now exists confirming the role of prolactin in human breast cancer. This evidence is evaluated and the argument presented that the tumorigenic risk from prolactin is therefore not species-specific to rodents but directly applies to humans. Further, as the mechanisms of prolactin-induced mammary tumor promotion and development appear analogous between rodents and humans, mammary tumorigenic findings in rodent carcinogenicity bioassays are both predictive and biologically relevant to the human response. Toxicologists and regulators need to consider this in carcinogenicity risk assessments. PMID- 22095847 TI - Life in the slow lane: the effect of reduced mobility on tadpole limb development. AB - Movement is thought to be a primary agent eliciting basic responses in the vertebrate body, such as the proper development of the musculoskeletal system. Embryos do not passively await hatching or birth but rather begin active movement very early on in their development. Most studies dealing with embryonic responses to changes in mobility have been performed in chickens or mammals. Herein, we investigate for the first time whether the embryos of organisms that are free living during development demonstrate the same morphological responses to reduced mobility as embryos that undergo development in controlled environments such as in utero or in a shelled egg. We changed the viscosity of the environment in which free-living anuran tadpoles grow by rearing them in an agar medium. We thus increased the viscosity of the growth medium resulting in a decrease in larval movement. We predicted that a substantial increase in viscosity of the medium in which the larvae were reared would have at least two consequences: (1) a reduction of tadpole mobility and (2) a delayed onset of skeletogenesis thus producing shorter long bones. Our predictions were upheld and tadpoles reared in an agar medium remain immobile longer and showed a delayed onset of skeletogenesis compared with controls. We propose that the developmental responses to the same stimulus are similar throughout tetrapods, regardless of their developmental context (i.e., intrauterine, within an egg, or free-living). PMID- 22095848 TI - The marriage of organocatalysis with metal catalysis: access to multisubstituted chiral 2,5-dihydropyrroles by cascade iminium/enamine-metal cooperative catalysis. PMID- 22095851 TI - From fertilization to cancer: a lifelong pursuit into how cells use oxygen. Otto Heinrich Warburg (October 8, 1883-August 1, 1970). PMID- 22095849 TI - Updating risk prediction tools: a case study in prostate cancer. AB - Online risk prediction tools for common cancers are now easily accessible and widely used by patients and doctors for informed decision-making concerning screening and diagnosis. A practical problem is as cancer research moves forward and new biomarkers and risk factors are discovered, there is a need to update the risk algorithms to include them. Typically, the new markers and risk factors cannot be retrospectively measured on the same study participants used to develop the original prediction tool, necessitating the merging of a separate study of different participants, which may be much smaller in sample size and of a different design. Validation of the updated tool on a third independent data set is warranted before the updated tool can go online. This article reports on the application of Bayes rule for updating risk prediction tools to include a set of biomarkers measured in an external study to the original study used to develop the risk prediction tool. The procedure is illustrated in the context of updating the online Prostate Cancer Prevention Trial Risk Calculator to incorporate the new markers %freePSA and [-2]proPSA measured on an external case-control study performed in Texas, U.S.. Recent state-of-the art methods in validation of risk prediction tools and evaluation of the improvement of updated to original tools are implemented using an external validation set provided by the U.S. Early Detection Research Network. PMID- 22095853 TI - 1hJFH coupling in 2-fluorophenol revisited: is intramolecular hydrogen bond responsible for this long-range coupling? AB - The present study shows that a hydrogen bond between the OH group and the fluorine atom is not involved in the (1h)J(FH) spin-spin coupling transmission either for 4-bromo-2-fluorophenol or 2-fluorophenol. In fact, according to a quantum theory of atoms in molecules analysis, no bond critical point is found between O-H and F moieties. The nature of the transmission mechanism of the Fermi contact term of the (1h)J(FH) spin-spin coupling is studied by analyzing canonical molecular orbitals (see J. Phys. Chem. A 2010, 114, 1044), and it is observed that virtual orbitals play only a quite minor role in its transmission. This is typical of a Fermi contact term transmitted mainly through exchange interactions owing to the overlap of proximate electronic clouds; therefore, it is suggested to identify them as (nTS)J(FH) coupling where n stands for the number of formal bonds separating the coupling nuclei. In the cases studied in this work is n = 4. Results presented in this work could provide an interesting rationalization for different experimental signs known in the current literature for proximate J(FH) couplings. PMID- 22095854 TI - Calculation of rate spectra from noisy time series data. AB - As the resolution of experiments to measure folding kinetics continues to improve, it has become imperative to avoid bias that may come with fitting data to a predetermined mechanistic model. Toward this end, we present a rate spectrum approach to analyze timescales present in kinetic data. Computing rate spectra of noisy time series data via numerical discrete inverse Laplace transform is an ill conditioned inverse problem, so a regularization procedure must be used to perform the calculation. Here, we show the results of different regularization procedures applied to noisy multiexponential and stretched exponential time series, as well as data from time-resolved folding kinetics experiments. In each case, the rate spectrum method recapitulates the relevant distribution of timescales present in the data, with different priors on the rate amplitudes naturally corresponding to common biases toward simple phenomenological models. These results suggest an attractive alternative to the "Occam's razor" philosophy of simply choosing models with the fewest number of relaxation rates. PMID- 22095855 TI - Protease-activated receptor 2 promotes experimental liver fibrosis in mice and activates human hepatic stellate cells. AB - Protease-activated receptor (PAR) 2 is a G-protein-coupled receptor that is activated after proteolytic cleavage by serine proteases, including mast cell tryptase and activated coagulation factors. PAR-2 activation augments inflammatory and profibrotic pathways through the induction of genes encoding proinflammatory cytokines and extracellular matrix proteins. Thus, PAR-2 represents an important interface linking coagulation and inflammation. PAR-2 is widely expressed in cells of the gastrointestinal tract, including hepatic stellate cells (HSCs), endothelial cells, and hepatic macrophages; however, its role in liver fibrosis has not been previously examined. We studied the development of CCl(4) -induced liver fibrosis in PAR-2 knockout mice, and showed that PAR-2 deficiency reduced the progression of liver fibrosis, hepatic collagen gene expression, and hydroxyproline content. Reduced fibrosis was associated with decreased transforming growth factor beta (TGFbeta) gene and protein expression and decreased matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinase 1 gene expression. In addition, PAR-2 stimulated activation, proliferation, collagen production, and TGFbeta protein production by human stellate cells, indicating that hepatic PAR-2 activation increases profibrogenic cytokines and collagen production both in vivo and in vitro. CONCLUSION: Our findings demonstrate the capacity of PAR-2 activation to augment TGFbeta production and promote hepatic fibrosis in mice and to induce a profibrogenic phenotype in human HSCs. PAR-2 antagonists have recently been developed and may represent a novel therapeutic approach in preventing fibrosis in patients with chronic liver disease. PMID- 22095856 TI - On a heuristic point of view concerning the expression of numerous genes during the cell cycle. AB - The current model of the eukaryotic cell cycle proposes that numerous genes are expressed at different times during the cell cycle. The existence of myriad control points for gene expression leads to theoretical and logical problems for cell cycle control. Each expressed gene requires a control element to appear in a cell-cycle specific manner; this control element requires another control element and so on, ad infinitum. There are also experimental problems with the current model based on ineffective synchronization methods and problems with microarray measurements of mRNA. Equally important, the efficacy of mRNA variation in affecting changes in protein content is negligible. An alternative view of the cell cycle proposes cycle-independent, invariant accumulation of mRNA during the cell cycle with decreases of specific proteins occurring only during the mitotic period of the cell cycle. PMID- 22095857 TI - Spectroscopic investigation on the interaction of Cr(VI) with bovine serum albumin. AB - The interaction of potassium dichromate (Cr(VI)) with bovine serum albumin (BSA) was investigated by fluorescence, synchronous fluorescence, resonance light scattering (RLS), ultraviolet-visible absorption, and circular dichroism (CD) spectroscopies under simulated physiological conditions. The experimental results showed that Cr(VI) could quench the intrinsic fluorescence of BSA following a static quenching process, which indicates the formation of a Cr(VI)-BSA complex. The binding constant (KA) and binding site (n) were measured at different temperatures. The spectroscopic results also revealed that the binding of Cr(VI) to BSA can lead to the loosening of the protein conformation and can change the microenvironment and skeleton of BSA. PMID- 22095858 TI - A FlAsH-based cross-linker to study protein interactions in living cells. AB - As you like it: xCrAsH, a dimeric derivative of the arsenical compound FlAsH, enables the highly specific, covalent cross-linking of two proteins containing a 12 amino acid peptide tag. This inducible and (by addition of dithiols) reversible system can be used to detect and manipulate protein-protein interactions both in vitro and in living cells (see picture). PMID- 22095859 TI - Contribution of taxane biosynthetic pathway gene expression to observed variability in paclitaxel accumulation in Taxus suspension cultures. AB - Variability in product accumulation is one of the major obstacles limiting the widespread commercialization of plant cell culture technology to supply natural product pharmaceuticals. Despite extensive process engineering efforts, which have led to increased yields, plant cells exhibit variability in productivity that is poorly understood. Elicitation of Taxus cultures with methyl jasmonate (MeJA) induces paclitaxel accumulation, but to varying extents in different cultures. In the current study, cultures with different aggregation profiles were established to create predictable differences in paclitaxel accumulation upon MeJA elicitation. Expression of known paclitaxel biosynthetic genes in MeJA elicited cultures exhibiting both substantial (15-fold) and moderate (2-fold) differences in paclitaxel accumulation was analyzed using quantitative reverse transcriptase PCR. Each population exhibited the characteristic large increase in paclitaxel pathway gene expression following MeJA elicitation; however, differences in expression between populations were minor, and only observed for the cultures with the 15-fold variation in paclitaxel content. These data suggest that although upregulation of biosynthetic pathway gene expression contributes to observed increases in paclitaxel synthesis upon elicitation with MeJA, there are additional factors that need to be uncovered before paclitaxel productivity can be fully optimized. PMID- 22095861 TI - Materials science in Madrid. PMID- 22095860 TI - Vascular endothelial growth factor receptor 2 (VEGFR2, Flk-1/KDR) protects HEK293 cells against CoCl(2) -induced hypoxic toxicity. AB - Vascular endothelial growth factor (VEGF) is an endothelium-specific mitogen and a promising inducer of angiogenesis and lymphangiogenesis. The VEGF receptors on endothelial cell membrane include the tyrosine kinases VEGFR-1 (Flt-1), VEGFR-2 (Flk-1/KDR) and VEGFR-3 (Flt-4). KDR is a major mediator of mitogenic, angiogenic and permeability-enhancing effects of VEGF. KDR is upregulated in response to hypoxia, a major inducer of VEGF gene transcription. A HEK293 cell line overexpressing KDR was established under cell hypoxic stress to explore the function of KDR. A hypoxia-inducing agent, cobalt chloride (CoCl(2)) was applied to detect whether KDR was able to prevent against chemical hypoxic toxicity. The results indicate that KDR attenuated CoCl(2)-induced cell injury in HEK293 cells. Furthermore, the underlying mechanisms may be explained by the increased expression of Bcl-2, AKT1 and phosphorylated AKT, key members of cell survival pathway, and decreased expression of pro-apoptosis protein Bax. PMID- 22095862 TI - Co-tunneling enhancement of the electrical response of nanoparticle networks. AB - A co-tunneling charge-transfer process dominates the electrical properties of a nanometer-sized "slice" in a nanoparticle network, which results in universal scaling of the conductance with temperature and bias voltage, as well as enhanced spintronics properties. By designing two large (10 MUm) electrodes with short (60 nm) separation, access is obtained to transport dominated by charge transfer involving "nanoslices" made of three nanoparticles only. Magnetic iron oxide nanoparticle networks exhibit a magnetoresistance ratio that is not reachable by tunneling or hopping processes, thereby illustrating how such a size-matched planar device with dominant co-tunneling charge-transfer process is optimal for realizing multifunctional devices with enhanced change of conductance under external stimulus. PMID- 22095863 TI - Silanol as a removable directing group for the Pd(II)-catalyzed direct olefination of arenes. AB - Need some direction? Silanol was developed as a directing group for the Pd(II) catalyzed oxidative Heck-type reaction of arenes. A one-pot C-H activation/desilylation process of benzyldiisopropylsilanol was also demonstrated, providing a powerful approach for the synthesis of ortho-alkenyl substituted alkylarenes. Considering the easily attachable and readily removable properties of the silanol group, this reaction will find broad synthetic applications. PMID- 22095864 TI - Speech processing: from peripheral to hemispheric asymmetry of the auditory system. AB - Language processing from the cochlea to auditory association cortices shows side dependent specificities with an apparent left hemispheric dominance. The aim of this article was to propose to nonspeech specialists a didactic review of two complementary theories about hemispheric asymmetry in speech processing. Starting from anatomico-physiological and clinical observations of auditory asymmetry and interhemispheric connections, this review then exposes behavioral (dichotic listening paradigm) as well as functional (functional magnetic resonance imaging and positron emission tomography) experiments that assessed hemispheric specialization for speech processing. Even though speech at an early phonological level is regarded as being processed bilaterally, a left-hemispheric dominance exists for higher-level processing. This asymmetry may arise from a segregation of the speech signal, broken apart within nonprimary auditory areas in two distinct temporal integration windows--a fast one on the left and a slower one on the right--modeled through the asymmetric sampling in time theory or a spectro temporal trade-off, with a higher temporal resolution in the left hemisphere and a higher spectral resolution in the right hemisphere, modeled through the spectral/temporal resolution trade-off theory. Both theories deal with the concept that lower-order tuning principles for acoustic signal might drive higher order organization for speech processing. However, the precise nature, mechanisms, and origin of speech processing asymmetry are still being debated. Finally, an example of hemispheric asymmetry alteration, which has direct clinical implications, is given through the case of auditory aging that mixes peripheral disorder and modifications of central processing. PMID- 22095865 TI - Hepatic retinoid levels in seven fish species (teleosts) from a tropical coastal lagoon receiving effluents from iron-ore mining and processing. AB - The present study was undertaken to investigate the possible effects of Fe and trace element exposure on hepatic levels of retinoids in seven fish species. Concentrations of retinoids were measured in fish collected from a coastal lagoon in Brazil that receives effluents from an iron-ore mining and processing plant. Fish from nearby coastal lagoons were also included to assess possible differences related to chemical exposure. Results indicated considerable differences in hepatic retinoid composition among the various species investigated. The most striking differences were in retinol and derivative specific profiles and in didehydro retinol and derivative-specific profiles. The Perciformes species Geophagus brasiliensis, Tilapia rendalli, Mugil liza, and Cichla ocellaris and the Characiforme Hoplias malabaricus were characterized as retinol and derivative-specific, while the Siluriformes species Hoplosternum littorale and Rhamdia quelen were didehydro retinol and derivative-specific fish species. A negative association was observed between Al, Pb, As, and Cd and hepatic didehydro retinoid levels. Fish with higher levels of hepatic Fe, Cu, and Zn showed unexpectedly significant positive correlations with increased hepatic retinol levels. This finding, associated with the positive relationships between retinol and retinyl palmitate with lipid peroxidation, may suggest that vitamin A is mobilized from other tissues to increase hepatic antioxidant levels for protection against oxidative damage. These data show significant but dissimilar associations between trace element exposure and hepatic retinoid levels in fish species exposed to iron-ore mining and processing effluents, without apparent major impacts on fish health and condition. PMID- 22095866 TI - Real-time reverse transcription polymerase chain reaction to measure mRNA: use, limitations, and presentation of results. PMID- 22095867 TI - Shine a light on jellyfish Cytaeis uchidae. PMID- 22095870 TI - Y does it work this way? Nettie Maria Stevens (July 7, 1861 - May 4, 1912). PMID- 22095868 TI - Caffeine alleviates the deterioration of Ca(2+) release mechanisms and fragmentation of in vitro-aged mouse eggs. AB - The developmental competence of mammalian eggs is compromised by postovulatory aging. We and others have found that in these eggs, the intracellular calcium ([Ca(2+)](i)) responses required for egg activation and initiation of development are altered. Nevertheless, the mechanism(s) underlying this defective Ca(2+) release is not well known. Here, we investigated if the function of IP(3)R1, the major Ca(2+) release channel at fertilization, was undermined in in vitro-aged mouse eggs. We found that in aged eggs, IP(3)R1 displayed reduced function as many of the changes acquired during maturation that enhance IP(3)R1 Ca(2+) conductivity, such as phosphorylation, receptor reorganization and increased Ca(2+) store content ([Ca(2+)](ER)), were lost with increasing postovulatory time. IP(3)R1 fragmentation, possibly associated with the activation of caspase 3, was also observed in these eggs. Many of these changes were prevented when the postovulatory aging of eggs was carried out in the presence of caffeine, which minimized the decline in IP(3)R(1) function and maintained [Ca(2+)](ER) content. Caffeine also maintained mitochondrial membrane potential, as measured by JC-1 fluorescence. We therefore conclude that [Ca(2+)](i) responses in aged eggs are undermined by reduced IP(3)R1 sensitivity, decreased [Ca(2+)](ER) , and compromised mitochondrial function, and that addition of caffeine ameliorates most of these aging-associated changes. Understanding the molecular basis of the protective effects of caffeine will be useful in elucidating, and possibly reversing, the signaling pathway(s) compromised by in vitro culture of eggs. PMID- 22095872 TI - Prediction of protein secondary structure from circular dichroism using theoretically derived spectra. AB - Circular dichroism (CD) is a spectroscopic technique commonly used to investigate the structure of proteins. Major secondary structure types, alpha-helices and beta-strands, produce distinctive CD spectra. Thus, by comparing the CD spectrum of a protein of interest to a reference set consisting of CD spectra of proteins of known structure, predictive methods can estimate the secondary structure of the protein. Currently available methods, including K2D2, use such experimental CD reference sets, which are very small in size when compared to the number of tertiary structures available in the Protein Data Bank (PDB). Conversely, given a PDB structure, it is possible to predict a theoretical CD spectrum from it. The methodological framework for this calculation was established long ago but only recently a convenient implementation called DichroCalc has been developed. In this study, we set to determine whether theoretically derived spectra could be used as reference set for accurate CD based predictions of secondary structure. We used DichroCalc to calculate the theoretical CD spectra of a nonredundant set of structures representing most proteins in the PDB, and applied a straightforward approach for predicting protein secondary structure content using these theoretical CD spectra as reference set. We show that this method improves the predictions, particularly for the wavelength interval between 200 and 240 nm and for beta-strand content. We have implemented this method, called K2D3, in a publicly accessible web server at http://www. ogic.ca/projects/k2d3. PMID- 22095873 TI - Synthesis and testing of a p-H2 hyperpolarized 13C probe based on the pyrazolo[1,5-a]pyrimidineacetamide DPA-713, an MRI vector to target the peripheral benzodiazepine receptors. AB - DPA-713 is the lead compound of a recently developed 2-phenylpyrazolo[1,5 a]pyrimidineacetamide series that has been shown to display a good targeting capability toward peripheral benzodiazepine receptors, recently renamed translocator protein (18 kDa) or in short TSPO. On the basis of this structure, a novel derivative bearing a [(13)C]butynoate moiety has been designed and synthesized (three steps-42% overall yield) providing, upon rapid and quantitative para-hydrogenation, the corresponding hyperpolarized [(13)C]alkene. Para-hydrogen-induced polarization effects have been detected in both (1)H and (13)C-NMR spectra. Upon applying a field cycling procedure, the spin order of para-H(2) added hydrogens is transferred on the (13)C carboxylate moiety yielding a signal enhancement of approximately 4500 times. T(1) of the carboxylate carbon atom is approximately 21.9 s (at 9.37 T). A (13)C-MR image has been acquired by using the (13)C RARE (Rapid Acquisition by Relaxation Enhancement) acquisition protocol on a 10-mM solution. The main limitation to the in vivo use of this novel para-hydrogenated [(13)C]derivative is its relatively low solubility in aqueous systems. PMID- 22095874 TI - Contribution of individual PKC isoforms to breast cancer progression. AB - The protein kinase C (PKC) family of serine/threonine kinases has been intensively studied in cancer since their discovery as major receptors for the tumor-promoting phorbol esters. The contribution of each individual PKC isozyme to malignant transformation is only partially understood, but it is clear that each PKC plays different role in cancer progression. PKC deregulation is a common phenomenon observed in breast cancer, and PKC expression and localization are usually dynamically regulated during mammary gland differentiation and involution. In fact, the overexpression of several PKCs has been reported in malignant human breast tissue and breast cancer cell lines. In this review, we summarize the knowledge available on the specific roles of PKC isoforms in the development, progression, and metastatic dissemination of mammary cancer. We also discuss the role of PKC isoforms as therapeutic targets, and their potential as markers for prognosis or treatment response. PMID- 22095875 TI - Lysine acetylation induced by chronic ethanol consumption impairs dynamin mediated clathrin-coated vesicle release. AB - The liver is the major site of ethanol metabolism and thus sustains the most injury from chronic alcohol consumption. Ethanol metabolism by the hepatocyte leads to the generation of reactive metabolites and oxygen radicals that can readily adduct DNA, lipids, and proteins. More recently, it has become apparent that ethanol consumption also leads to increased post-translational modifications of the natural repertoire, including lysine hyperacetylation. Previously, we determined that alcohol consumption selectively impairs clathrin-mediated internalization in polarized hepatocytes. However, neither the step at which the block occurs nor the mechanism responsible for the defect have been identified. To identify the specific step at which clathrin-mediated internalization is impaired, we examined the distributions, levels, and assembly of selected components of the clathrin machinery in control and ethanol-treated cells. To determine whether the impairment is caused by ethanol-induced lysine acetylation, we also examined the same coat components in cells treated with trichostatin A (TSA), a deacetylase inhibitor that leads to protein hyperacetylation in the absence of ethanol. CONCLUSION: We determined that both ethanol and TSA impair internalization at a late stage before vesicle fission. We further determined that this defect is likely the result of decreased dynamin recruitment to the necks of clathrin-coated invaginations resulting in impaired vesicle budding. These results also raise the exciting possibility that agents that promote lysine deacetylation may be effective therapeutics for the treatment of alcoholic liver disease. PMID- 22095876 TI - Hydrogen production coupled to hydrocarbon oxygenation from photocatalytic water splitting. PMID- 22095877 TI - Optimization of endothelial cell growth in a murine in vitro blood-brain barrier model. AB - In vitro cell culture models of the blood-brain barrier (BBB) are important tools used to study cellular physiology and brain disease therapeutics. Although the number of model configurations is expanding across neuroscience laboratories, it is not clear that any have been effectively optimized. A sequential screening study to identify optimal primary mouse endothelial cell parameter set points, grown alone and in combination with common model enhancements, including co culturing with primary mouse or rat astrocytes and addition of biochemical agents in the media, was performed. A range of endothelial cell-seeding densities (1-8 * 10(5) cells/cm(2) ) and astrocyte-seeding densities (2-8 * 10(4) cells/cm(2) ) were studied over seven days in the system, and three distinct media-feeding strategies were compared to optimize biochemical agent exposure time. Implementation of all optimal set points increased transendothelial electrical resistance by over 200% compared to an initial model and established a suitable in vitro model for brain disease application studies. These results demonstrate the importance of optimizing cell culture growth, which is the most important parameter in creating an in vitro BBB model as it directly relates the model to the in vivo arrangement. PMID- 22095878 TI - Chiral nanoporous metal-organic frameworks with high porosity as materials for drug delivery. AB - A chiral nanoporous metal-organic framework (MOF) with high porosity is obtained based on nontoxic zinc and achiral hexadentate ligand. It shows high drug loading and slow release of the proportion of the loaded drug with a complete delivery time of about one week when used as a material for adsorption and delivery of anticancer 5-fluorouracil. PMID- 22095879 TI - Off-target immune cell toxicity caused by AG-012986, a pan-CDK inhibitor, is associated with inhibition of p38 MAPK phosphorylation. AB - AG-012986 is a pan-CDK (cyclin-dependent kinase) inhibitor that has in vitro and in vivo antitumor properties but was stopped in development due in part to rapid bone-marrow-independent white blood cell toxicity in preclinical studies and the potential for acute and delayed immunosuppression in humans. Because peripheral lymphocytes are largely nonproliferating, it was hypothesized the toxicity of AG 012986 was due to an off-target mechanism and not driven by the intended pharmacology. We show the toxicity mechanism in primary human immune cells is caspase driven. T-cells treated with AG-012986 and acutely stimulated through the T-cell receptor exhibited decreased toxicity while still maintaining cell division inhibition. This indicated that the pharmacology of AG-012986 functioned as expected but the toxicity had now been decoupled through activation. Induced phosphorylation of p38 and IL-2 production was impaired with AG-012986. Thus, AG 012986 could cause apoptosis of T-cells by targeting upstream kinases in the p38 Mitogen-activated protein kinase (MAPK) pathway and impairing cellular survival. PMID- 22095880 TI - Otolaryngology fantastica: the ear, nose, and throat manifestations of Munchausen's syndrome. AB - OBJECTIVES/HYPOTHESIS: Munchausen's syndrome (MS) is a form of severe, chronic, factitious disorder with physical symptoms. Some essential features define MS, such as recurrent, feigned, or simulated illness; peregrination (traveling or wandering); pseudologia fantastica; and drug abuse. Munchausen's syndrome by proxy (MSBP) classically involves a parent or other caregiver who inflicts injury or induces illness in a child. The aim of the present study was to summarize and study the main ear, nose, and throat (ENT) manifestations of MS and MSBP. STUDY DESIGN: A systematic literature review carried out in a tertiary university referral center. METHODS: An appropriate string was run on PubMed to retrieve articles dealing with ENT manifestations of MS and MSBP. A double cross-check was performed on citations and full-text articles found using selected inclusion and exclusion criteria. RESULTS: In total, 24 articles were finally included in the study, describing 30 cases of MS or MSBP involving the ENT region; 15/30 (50%) cases involved the face, most often presenting as facial pain or facial swelling; and 7/30 (23.3%) cases presented with symptoms involving the ear. Six cases out of 30 (20%) were MSBP. CONCLUSIONS: MS and MSBP may present with symptoms involving the head and neck area, particularly the face and external ear canal. The ENT specialist should suspect MS in patients with strange and long-lasting symptoms, so as to avoid misdiagnosis and unnecessary treatments that waste time and money in the healthcare sector. PMID- 22095881 TI - Effects of 2-methoxyestradiol on proliferation, apoptosis and gene expression of cyclin B1 and c-Myc in esophageal carcinoma EC9706 cells. AB - 2-Methoxyestradiol (2-ME) is an endogenous metabolite of 17beta-estradiol. In this study, we determined the antitumour activities of 2-ME on the well differentiated EC9706 esophageal carcinoma cells in vitro. 2-ME had a strong antiproliferative effect on EC9706 cells and caused an increase in the population of apoptotic cells, detected by flow cytometry. A significant number of cells were blocked in the G(2)/M phase of the cell cycle. 2-ME-treated cells demonstrated an increase in cyclin B1 and c-Myc protein levels, as well as an increase in the percentage of G(2)/M phase. Their up-regulation may be involved in 2-ME-induced apoptosis and G(2)/M cell cycle arrest of the EC9706 cells, and it precedes the onset of apoptosis. PMID- 22095882 TI - Delayed photoelectron transfer in Pt-decorated CdS nanorods under hydrogen generation conditions. AB - Noble-metal-decorated colloidal semiconductor nanocrystals are currently receiving significant attention for photocatalytic hydrogen generation. A detailed knowledge of the charge-carrier dynamics in these hybrid systems under hydrogen generation conditions is crucial for improving their performance. Here, a transient absorption spectroscopy study is conducted on colloidal, Pt-decorated CdS nanorods addressing this issue. Surprisingly, under hydrogen generation conditions (i.e., in the presence of the hole-scavenger sodium sulfite), photoelectron transfer to the catalytically active Pt is slower than without the hole scavenger, where no significant hydrogen generation occurs. This unexpected behavior can be explained by different degrees of localization of the electron wavefunction in the presence and absence of holes on the nanorods, which modify the electron transfer rates to the Pt. The results show that solely optimizing charge transfer rates in photocatalytic nanosystems is no guarantee of improved performance. Instead, the collective Coulomb interaction-mediated electron-hole dynamics need to be considered. PMID- 22095883 TI - The pharmacological mechanism of angiotensin-converting enzyme inhibition by green tea, Rooibos and enalaprilat - a study on enzyme kinetics. AB - Green tea (Camellia sinensis L.) and Rooibos (Aspalathus linearis Dahlg.) inhibit angiotensin-converting enzyme (ACE) in vitro and in vivo. The ACE inhibitor enalaprilat has been described previously as a competitive inhibitor and sometimes as a non-competitive inhibitor. The aim of this study was to investigate the pharmacological mechanism of ACE inhibition of green tea and Rooibos by enzyme kinetics, and to compare this with enalaprilat. A Michaelis Menten kinetics and Lineweaver-Burk graph showed mean values of V(max) = 3.73 uM and K(m) = 0.71 uM for green tea, of V(max) = 6.76 uM and K(m) = 0.78 uM for Rooibos, of V(max) = 12.54 uM and K(m) = 2.77 uM for enalaprilat, and of V(max) = 51.33 uM and K(m) = 9.22 uM for the PBS control. Incubating serum with green tea or Rooibos saturated with zinc chloride did not change the inhibitory effect. Enalaprilat preincubated with zinc chloride showed a decrease in the inhibitory effect. In conclusion, green tea, Rooibos and enalaprilat seem to inhibit ACE activity using a mixed inhibitor mechanism. PMID- 22095884 TI - Mutations in the Notch pathway alter the patterning of multifidus. AB - Clinical studies have suggested that defects in the epaxial muscles, particularly multifidus, may contribute to the etiology of idiopathic scoliosis. While the epaxial muscles and the vertebrae derive from the same embryonic segmentation process, the mechanisms that pattern the multisegmental back muscles are still unclear. The process of segmentation is regulated by the Notch signaling pathway, and mutations in the modulators delta-like 3 (Dll3) and lunatic fringe (Lfng) are genetic models for spinal disorders such as scoliosis. Osteological defects have been characterized in these genetic models, but myological phenotypes have not previously been studied. We analyzed the multifidus muscle in the mouse (Mus musculus) and observed intriguing changes in the cranio-caudal borders of multifidus in Dll3 and Lfng models. Statistical analysis did not find a significant association between the majority of the multifidus anomalies and the vertebral defects, suggesting a previously unappreciated role for Notch signaling in patterning epaxial muscle groups. These findings indicate an additional mechanism by which DLL3 and LFNG may play a role in the etiology of human idiopathic scoliosis. PMID- 22095885 TI - Detection of retinoic acid receptor agonistic activity and identification of causative compounds in municipal wastewater treatment plants in Japan. AB - Retinoic acid (RA) receptor (RAR) agonists are potential toxicants that can cause teratogenesis in vertebrates. To determine the occurrence of RAR agonists in municipal wastewater treatment plants (WWTPs), we examined the RARalpha agonistic activities of influent and effluent samples from several municipal WWTPs in Osaka, Japan, using a yeast two-hybrid assay. Significant RARalpha agonistic activity was detected in all the influent samples investigated, suggesting that municipal wastewater consistently contains RAR agonists. Fractionations using high-performance liquid chromatography, directed by the bioassay, found several bioactive peaks from influent samples. The RAR agonists, all-trans RA (atRA), 13 cis RA (13cRA), 4-oxo-atRA, and 4-oxo-13cRA, possibly arising from human urine, were identified by liquid chromatography ion trap time-of-flight mass spectrometry. Quantification of the identified compounds in municipal WWTPs confirmed that they were responsible for the majority of RARalpha agonistic activity in WWTP influents, and also revealed they were readily removed from wastewater by activated sludge treatment. Simultaneous measurement of the RARalpha agonistic activity revealed that although total activity typically declined concomitant with the reduction of the four identified compounds, it remained high after the decline of RAs and 4-oxo-RAs in one WWTP, suggesting the occurrence of unidentified RAR agonists during the activated sludge treatment. PMID- 22095886 TI - Observer variation in the histopathologic assessment of extranodal tumor spread in lymph node metastases in the neck. AB - BACKGROUND: Extranodal spread (ENS) of tumors is widely used as a prognosticator for patients with head and neck cancer and is used as an indicator for postoperative treatment. However, the histopathologic agreement among pathologists on the assessment of the presence or absence of this criterion has never been studied. METHODS: The interobserver and intraobserver agreement among 10 pathologists on the diagnosis of ENS in 41 tumor-positive lymph nodes was evaluated. RESULTS: The kappa value of the interobserver agreement among pathologists varied between 0.14 and 0.75, the overall kappa value was 0.42 and 0.49 in the 2 scoring sessions. The intraobserver kappa value varied between 0.49 and 0.95. CONCLUSION: The intraobserver and interobserver agreement among pathologists in the assessment of the presence of ENS was low in metastatic lymph nodes in the neck. Because of the widely accepted prognostic significance and therapeutic consequences of ENS, there is a need for internationally accepted reproducible criterion for the histopathologic assessment of ENS in metastatic lymph nodes in the neck. PMID- 22095887 TI - Discrepancies in glomerular and tubulointerstitial/vascular immune complex IgG subclasses in lupus nephritis. AB - BACKGROUND AND OBJECTIVES: Lupus nephritis is characterized by glomerular and extraglomerular immune complex deposition in the kidney. It is unclear whether the same circulating immune complexes deposit in the glomeruli and in extraglomerular structures, or whether they are pathogenetically different. Differences in the IgG subclass composition may point towards different pathways in the formation of glomerular and extraglomerular immune complexes. Therefore we investigated IgG subclass distribution in the immune complex deposits at these anatomic sites. DESIGN: A total of 84 biopsies diagnosed as lupus nephritis and classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification, were examined by direct immunofluorescence staining for IgG subclasses. The IgG subclass composition in the glomerular, tubular basement membrane (TBM) and vascular wall deposits was compared. We also correlated the presence/absence of interstitial inflammation and IgG subclasses in the TBM and vascular deposits. Lastly, we looked for correlation between staining for IgG subclasses and complement C1q and C3 staining. RESULTS: IgG staining was present in the TBM in 52/84 biopsies, and in the vascular walls in 40/84 biopsies. IgG subclass distribution was discrepant between glomerular and TBM deposits in 36/52 biopsies, and between glomerular and vascular deposits in 27/40 biopsies. Interstitial inflammation did not correlate with the presence of IgG staining or distribution of IgG subclasses in the TBM. Interstitial inflammation was more common in biopsies of African-American patients than Caucasian patients. The IgG subclass staining correlated with C1q staining in all the three compartments. CONCLUSIONS: The antibody composition of the glomerular and extraglomerular immune complex deposits appear to differ from each other. They may not represent the same preformed immune complexes from the circulation. It is likely that their pathogenesis and site of formation are different. PMID- 22095888 TI - Role of reactive intermediates in the immunopathogenesis of the pristane-induced Balb/c model of lupus. AB - Pristane-induced lupus in Balb/c mice represents an environmentally induced lupus model which is widely used for unravelling the mystery of the pathogenesis of the disease. An intraperitoneal innate immune reaction to pristane is primarily accountable for the development of the systemic lupus erythematosus-like disease in the model. In this study, reactive oxygen species (ROS) and nitric oxide (NO) levels were assessed (as a measure of chronic inflammation) in the peritoneum of the Balb/c model of SLE-like disease 6 months after a single intraperitoneal injection of pristane. Levels of ROS in peritoneal macrophages were significantly enhanced (mean fluorescence value +/- SD: 648 +/- 100.9) in pristane-treated mice (PT) as compared with control mice (mean fluorescence value +/- SD: 79 +/ 7.8) treated with phosphate buffer saline (PBST). An immunofluorescence study reveal the localization of ROS within nuclei, suggesting oxidative damage. Similarly, levels of NO were also markedly raised in PT mice (34.71 umol/l +/- 8.48) as compared with PBST mice (1.36 nmol/l +/- 0.14). These new findings lead to speculation about the role of reactive intermediates in the development of disease. This study proposes that the sustained production of reactive intermediates during chronic intraperitoneal inflammation might reduce antioxidant defences and lead to a condition of oxidative stress, which might further be responsible for this autoimmune condition. PMID- 22095889 TI - The Systemic Lupus International Collaborating Clinics (SLICC) group - it was 20 years ago today. AB - The Systemic Lupus International Collaborating Clinics (SLICC) group is 20 years old this year (2011). This brief review traces the origins of the group focussing on its more recent history and reviewing some of its major contributions to lupus research during the past two decades. PMID- 22095891 TI - Topology-selective chromatography reveals plasmid supercoiling shifts during fermentation and allows rapid and efficient preparation of topoisomers. PMID- 22095892 TI - Development and status of health insurance systems in China. AB - Health insurance programs have changed rapidly over time in China. Among rural populations, insurance coverage shifted from nearly universal levels in the 1970s to 7% in 1999; it stands at 94% of counties in 2009. This large increase is the result of a series of health reforms that aim to achieve universal access to healthcare and better risk protection, largely through the rollout of the health insurance programs and the gradual increase in subsidies and benefits over time. In this paper, we present the development of the rural and urban health insurance programs, their modes of financing and operation and the benefits and reimbursement schemes at the end of 2009. We discuss some of the problems with the rural and urban residents' schemes including reliance on local government capacity, reimbursement ceilings and rates, and incentives for unnecessary care and waste in the design of the programs. Recommendations include increasing financial support and deepening the benefits packages. Strategies to control cost and improve quality include developing mixed provider payment mechanisms, implementing essential medicines policies and strengthening the quality of primary-care provision. PMID- 22095893 TI - Albumin infusion in patients undergoing large-volume paracentesis: a meta analysis of randomized trials. AB - Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites, as compared with no treatment. Treatment alternatives to albumin, such as artificial colloids and vasoconstrictors, have been widely investigated. The aim of this meta-analysis was to determine whether morbidity and mortality differ between patients receiving albumin versus alternative treatments. The meta-analysis included randomized trials evaluating albumin infusion in patients with tense ascites. Primary endpoints were postparacentesis circulatory dysfunction, hyponatremia, and mortality. Eligible trials were sought by multiple methods, including computer searches of bibliographic and abstract databases and the Cochrane Library. Results were quantitatively combined under a fixed-effects model. Seventeen trials with 1,225 total patients were included. There was no evidence of heterogeneity or publication bias. Compared with alternative treatments, albumin reduced the incidence of postparacentesis circulatory dysfunction (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.27-0.55). Significant reductions in that complication by albumin were also shown in subgroup analyses versus each of the other volume expanders tested (e.g., dextran, gelatin, hydroxyethyl starch, and hypertonic saline). The occurrence of hyponatremia was also decreased by albumin, compared with alternative treatments (OR, 0.58; 95% CI, 0.39-0.87). In addition, mortality was lower in patients receiving albumin than alternative treatments (OR, 0.64; 95% CI, 0.41-0.98). CONCLUSIONS: This meta analysis provides evidence that albumin reduces morbidity and mortality among patients with tense ascites undergoing large-volume paracentesis, as compared with alternative treatments investigated thus far. PMID- 22095894 TI - Exploring frataxin function. AB - Frataxin is a nuclear-encoded mitochondrial protein highly conserved in prokaryotes and eukaryotes. Its deficiency was initially described as the phenotype of Friedreich's ataxia, an autosomal recessive disease in humans. Although several functions have been described for frataxin, that is, involvement in Fe-S cluster and heme synthesis, energy conversion and oxidative phosphorylation, iron handling and response to oxidative damage, its precise function remains unclear. Although there is a general consensus on the participation of frataxin in the maintenance of cellular iron homeostasis and in iron metabolism, this protein may have other specific functions in different tissues and organisms. PMID- 22095895 TI - Morphology-driven modulation of charge transport in radical/ion-containing, self assembled block copolymer platform. AB - A TEMPO-substituted ionic liquid was selectively incorporated into well-defined, self-assembled block copolymer templates, which served as an active layer for organic nonvolatile memory. Phase structures (sphere, cylinder, and lamellae) and their orientation modulated the resistive switching behavior, which demonstrated the unprecedented, morphology-driven charge transport in the organic electronic devices. PMID- 22095896 TI - Identification of 1,3-diiminoisoindoline carbohydrazides as potential antimalarial candidates. AB - A series of inhibitors of plant enzymes of the non-mevalonate pathway from herbicide research efforts at BASF were screened for antimalarial activity in a cell-based assay. A 1,3-diiminoisoindoline carbohydrazide was found to inhibit the growth of Plasmodium falciparum with an IC(50) value <100 nM. Synthesis of a variety of derivatives allowed an improvement of the initial antimalarial activity down to IC(50) =18 nM for the most potent compound, the establishment of a structure-activity relationship, and the evaluation of the cytotoxic profile of the diiminoisoindolines. Furthermore, interesting configurational and conformational aspects for this class of compounds were studied by computational and X-ray crystal structure analysis. Some of the compounds can act as tridentate ligands, forming 2:1 ligand-iron(III) complexes, which also display antimalarial activity in the nanomolar IC(50) range, paired with low cytotoxicity. PMID- 22095897 TI - Passive sampling provides evidence for Newark Bay as a source of polychlorinated dibenzo-p-dioxins and furans to the New York/New Jersey, USA, atmosphere. AB - Freely dissolved and gas phase polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were measured in the water column and atmosphere at five locations within Newark Bay (New Jersey, USA) from May 2008 to August 2009 with polyethylene (PE) passive samplers. Mono- to octa-CDDs and mono- to hepta-CDFs were detected in bottom and surface waters at <= 20 pg/L with no clear gradient between sampling locations, suggesting freely dissolved PCDD/Fs are well mixed in Newark Bay. The most concentrated, freely dissolved gas phase congener was 2,7/2,8-dichlorodibenzo-p-dioxin (2,7/2,8-DiCDD), likely originating from photochemical conversion of triclosan in Newark Bay. Air-surface water gradients strongly favored net volatilization of PCDD/PCDFs from Newark Bay. Water-to-air fluxes of 2,7/2,8-DiCDD and 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), the most concentrated and the most toxic PCDD/PCDFs, respectively, were approximately 60 ng/m(2) per month and 14 to 51 pg/m(2) per month. Significant decreases in freely dissolved 2,3,7,8-TCDD concentrations with increasing freshwater near the Passaic River and conservative behavior during the summer of 2009 suggested Passaic sediments as a likely source of 2,3,7,8-TCDD to Newark Bay. Mass balance calculations implied that almost 50% of freely dissolved 2,3,7,8-TCDD delivered to Newark Bay from the Hackensack and Passaic Rivers was lost to volatilization in the summer of 2009. PMID- 22095899 TI - New triblock copolymer templates, PEO-PB-PEO, for the synthesis of titania films with controlled mesopore size, wall thickness, and bimodal porosity. AB - The synthesis and properties of a series of new structure-directing triblock copolymers with PEO-PB-PEO structure (PEO = poly(ethylene oxide) and PB = polybutadiene) and their application as superior pore-templates for the preparation of mesoporous titania coatings are reported. Starting from either TiCl4 or from preformed TiO2 nanocrystalline building blocks, mesoporous crystalline titanium oxide films with a significant degree of mesoscopic ordered pores are derived, and the pore size can be controlled by the molecular mass of the template polymer. Moreover, the triblock copolymers form stable micelles already at very low concentration, i.e., prior to solvent evaporation during the evaporation-induced self-assembly process (EISA). Consequently, the thickness of pore walls can be controlled independently of pore size by changing the polymer to-precursor ratio. Thus, unprecedented control of wall thickness in the structure of mesoporous oxide coatings is achieved. In addition, the micelle formation of the new template polymers is sufficiently distinct from that of typical commercial PPO-PEO-PPO polymers (Pluronics; PPO = poly(propylene oxide)), so that a combination of both polymers facilitates bimodal porosity via dual micelle templating. PMID- 22095898 TI - RGD peptide-modified adenovirus expressing hepatocyte growth factor and X-linked inhibitor of apoptosis improves islet transplantation. AB - BACKGROUND: Islet transplantation has the potential for treating type I diabetes; however, its widespread clinical application is limited by the massive apoptotic cell death and poor revascularization of transplanted islet grafts. METHODS: We constructed a surface-modified adenoviral vector with RGD (Arg-Gly-Asp) sequences encoding human X-linked inhibitor of apoptosis and hepatocyte growth factor (RGD Adv-hHGF-hXIAP). In vitro transgene expression in human islets was determined by enzyme-liniked immunosorbent assay. RGD-Adv-hHGF-hXIAP-transduced human islets were transplanted under the kidney capsule of streptozotocin-induced diabetic NOD/SCID mice. The blood glucose levels of mice were measured weekly. The kidneys bearing islets were isolated at the end of the experiment and subjected to immunofluorescence staining. RESULTS: The transduction efficiency on human islets was significantly improved using RGD-modified adenovirus. HGF and XIAP gene expressions were dose-dependent after viral transduction. When exposed to a cocktail of inflammatory cytokines, RGD-Adv-hHGF-hXIAP-transduced human islets showed decreased caspase 3 activity and reduced apoptotic cell death. Prolonged normoglycemic control could be achieved by transplanting RGD-Adv-hHGF-hXIAP transduced human islets. Immunofluorescence staining of kidney sections bearing RGD-Adv-hHGF-hXIAP-transduced islets was positive for insulin and von Willebrand factor (vWF) at 200 days after transplantation. CONCLUSIONS: These results indicated that ex vivo transduction of islets with RGD-Adv-hHGF-hXIAP decreased apoptotic islet cell death and improved islet revascularization, and eventually might improve the outcome of human islet transplantation. PMID- 22095900 TI - Video laryngoscopy-assisted secondary tracheoesophageal puncture placement for the patient with severely limited neck extension. AB - Secondary tracheoesophageal puncture (TEP) placement in patients with severe limitations in neck extension is challenging. Visualization of the hypopharynx with traditional rigid endoscopy may not be possible. We report using the C-MAC (Karl Storz, Tuttlingen, Germany) video laryngoscope to successfully place a secondary TEP in patient with severe radiation fibrosis at a tertiary referral center. A 59-year-old male with severe radiation fibrosis of the neck underwent total laryngectomy for a nonfunctioning larynx. His primary TEP dislodged in the early postoperative period and the patient requested secondary TEP and voice prosthesis. The result was a successful, properly positioned, placement of a secondary TEP. Videolaryngoscopy should be included in the surgeon's armamentarium of techniques to effectively and safely perform secondary TEP in anatomically difficult patients. PMID- 22095901 TI - Induction of apoptosis by type Ibeta protein kinase G in the human breast cancer cell lines MCF-7 and MDA-MB-468. AB - Activation of protein kinase G (PKG) by cyclic guanosine 3,5-monophosphate (cGMP) has become of considerable interest as a novel molecular approach for the induction of apoptosis in cancer cells. This study was conducted to investigate the role of PKG isoforms in the regulation of cell growth in human breast cancer cell lines MCF-7 and MDA-MB468. The expression levels of PKG isoforms were also examined using real-time reverse transcriptase polymerase chain reaction. No differences in the gene expression of PKG isoforms were observed between MCF-7 and MDA-MB-468 cells. To investigate the effects of PKG isoforms on the regulation of cell growth, the cGMP analogues 8-APT-cGMP (PKGIalpha activator), 8 Br-PET-cGMP (PKGIbeta activator) and 8-pCPT-cGMP (PKGII activator) were employed. Apoptosis was assessed with the Annexin-V-propidium iodide (PI) staining, cell cycle analysis and caspase-3/9 activity assay. Treatment of MCF-7 and MDA-MB-468 cells with 8-Br-PET-cGMP resulted in a concentration-dependent cell growth inhibition and apoptosis, whereas neither PKGIalpha nor PKGII activators had any effect on the cell growth. The role of PKGIbeta in the inhibition of cell growth was confirmed using PKGI and PKGII inhibitors. The present study is the first to demonstrate the involvement of PKGIbeta in the inhibition of cell growth and induction of apoptosis in breast cancer cells. PMID- 22095903 TI - Effects of precaudal elongation on visceral topography in a basal clade of ray finned fishes. AB - Elongate body forms have evolved numerous times independently within Vertebrata. Such body forms have evolved in large part via changes to the vertebral column, either through addition or lengthening of vertebrae. Previous studies have shown that body elongation in fishes has evolved most frequently through the addition of caudal vertebrae. In contrast, however, body elongation in Polypteriformes, a basal clade of ray-finned fishes (Actinopterygii), has evolved through the addition of precaudal vertebrae; one genus, Erpetoichthys, has approximately twice as many precaudal vertebrae as do members of its sister genus, Polypterus. Thus, polypteriform fishes provide an excellent opportunity to study the effects of precaudal elongation on the gross morphology and organization of visceral organs contained within the body cavity. In this study, we document the anteroposterior positions of most major visceral organs in representative species of both genera (E. calabaricus and P. palmas), relative to both vertebral number and percent pre-anal length. We found that, whereas the positions of the anterior and posterior borders of the visceral organs relative to percent pre-anal length were generally similar between the two species, most visceral organs were positioned further posteriorly in E. calabaricus than in P. palmas with respect to vertebral number. Based on previous determinations of the molecular control of anteroposterior patterning of the visceral organs, we discuss which possible changes in gene expression may have led to the anatomical modifications seen in the visceral morphology of Erpetoichthys. PMID- 22095902 TI - Biological activities of Indian celery, Seseli diffusum (Roxb. ex Sm.) Sant. & Wagh. AB - In continuation of our work on Indian celery (Seseli diffusum (Roxb. ex Sm.) Santapau & Wagh; Umbelliferae), the fractionation of the 80% MeOH-H(2) O extract of the seeds was performed to identify the principles responsible for its folk use as an antispasmodic and diuretic. Several compounds were isolated as active components: seselin (1) and anthriscinol methyl ether (4) showed a selective cytotoxicity to some yeast strains. Compound 1 also showed spasmolytic activity. On the other hand, isopimpinellin (3) and isorutarin (5) exhibited a spasmogenic effect on the smooth muscle preparations. Compound 5 was also found to have antioxidant activity. Among them, compound 4 was isolated for the first time from this plant. PMID- 22095905 TI - Covalent capture of nitrous oxide by N-heterocyclic carbenes. PMID- 22095904 TI - EGRI and FOSB gene expressions in cancer stroma are independent prognostic indicators for epithelial ovarian cancer receiving standard therapy. AB - Stromal components interact with cancer cells to promote growth and metastasis. The purpose of this study was to identify genes expressed in stroma, which could provide prognostic information in epithelial ovarian cancer (EOC). Seventy-four patients were included. We performed gene expression profiling and confirmed array data using RT-PCR and immunohistochemistry. By microarray analysis, 52 candidate genes associated with progression free survival (PFS) were identified (P < 0.005). Expression of the early growth response 1 (EGR1) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) genes was further analyzed. Array data were confirmed by RT-PCR and multivariate analysis demonstrated that both EGR1 and FOSB expression in cancer stroma, and EGR1 expression in cancer are independent prognostic factors in EOC. Immunohistochemically, EGR1 protein is localized in cancer cells and alpha-smooth muscle actin positive stromal fibroblasts. The EGR1 and FOSB expression in stromal cells and EGR1 expression in cancer cells are prognostic indicators in EOC. PMID- 22095907 TI - Antibacterial components of honey. AB - The antibacterial activity of honey has been known since the 19th century. Recently, the potent activity of honey against antibiotic-resistant bacteria has further increased the interest for application of honey, but incomplete knowledge of the antibacterial activity is a major obstacle for clinical applicability. The high sugar concentration, hydrogen peroxide, and the low pH are well-known antibacterial factors in honey and more recently, methylglyoxal and the antimicrobial peptide bee defensin-1 were identified as important antibacterial compounds in honey. The antibacterial activity of honey is highly complex due to the involvement of multiple compounds and due to the large variation in the concentrations of these compounds among honeys. The current review will elaborate on the antibacterial compounds in honey. We discuss the activity of the individual compounds, their contribution to the complex antibacterial activity of honey, a novel approach to identify additional honey antibacterial compounds, and the implications of the novel developments for standardization of honey for medical applications. PMID- 22095908 TI - PS-b-P3HT copolymers as P3HT/PCBM interfacial compatibilizers for high efficiency photovoltaics. AB - A conducting diblock copolymer of PS-b-P3HT was added to serve as a compatibilizer in a P3HT/PCBM blend, which improved the power-conversion efficiency from 3.3% to 4.1% due to the enhanced crystallinity, morphology, interface interaction, and depth profile of PCBM. PMID- 22095906 TI - STITCHER: Dynamic assembly of likely amyloid and prion beta-structures from secondary structure predictions. AB - The supersecondary structure of amyloids and prions, proteins of intense clinical and biological interest, are difficult to determine by standard experimental or computational means. In addition, significant conformational heterogeneity is known or suspected to exist in many amyloid fibrils. Previous work has demonstrated that probability-based prediction of discrete beta-strand pairs can offer insight into these structures. Here, we devise a system of energetic rules that can be used to dynamically assemble these discrete beta-strand pairs into complete amyloid beta-structures. The STITCHER algorithm progressively 'stitches' strand-pairs into full beta-sheets based on a novel free-energy model, incorporating experimentally observed amino-acid side-chain stacking contributions, entropic estimates, and steric restrictions for amyloidal parallel beta-sheet construction. A dynamic program computes the top 50 structures and returns both the highest scoring structure and a consensus structure taken by polling this list for common discrete elements. Putative structural heterogeneity can be inferred from sequence regions that compose poorly. Predictions show agreement with experimental models of Alzheimer's amyloid beta peptide and the Podospora anserina Het-s prion. Predictions of the HET-s homolog HET-S also reflect experimental observations of poor amyloid formation. We put forward predicted structures for the yeast prion Sup35, suggesting N-terminal structural stability enabled by tyrosine ladders, and C-terminal heterogeneity. Predictions for the Rnq1 prion and alpha-synuclein are also given, identifying a similar mix of homogenous and heterogeneous secondary structure elements. STITCHER provides novel insight into the energetic basis of amyloid structure, provides accurate structure predictions, and can help guide future experimental studies. PMID- 22095909 TI - Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy. AB - Elevated serum ferritin levels may reflect a systemic inflammatory state as well as increased iron storage, both of which may contribute to an unfavorable outcome of chronic hepatitis C (CHC). We therefore performed a comprehensive analysis of the role of serum ferritin and its genetic determinants in the pathogenesis and treatment of CHC. To this end, serum ferritin levels at baseline of therapy with pegylated interferon-alpha and ribavirin or before biopsy were correlated with clinical and histological features of chronic hepatitis C virus (HCV) infection, including necroinflammatory activity (N = 970), fibrosis (N = 980), steatosis (N = 886), and response to treatment (N = 876). The association between high serum ferritin levels (> median) and the endpoints was assessed by logistic regression. Moreover, a candidate gene as well as a genome-wide association study of serum ferritin were performed. We found that serum ferritin >= the sex-specific median was one of the strongest pretreatment predictors of treatment failure (univariate P < 0.0001, odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.34-0.60). This association remained highly significant in a multivariate analysis (P = 0.0002, OR = 0.35, 95% CI = 0.20-0.61), with an OR comparable to that of interleukin (IL)28B genotype. When patients with the unfavorable IL28B genotypes were stratified according to high versus low ferritin levels, SVR rates differed by > 30% in both HCV genotype 1- and genotype 3-infected patients (P < 0.001). Serum ferritin levels were also independently associated with severe liver fibrosis (P < 0.0001, OR = 2.67, 95% CI = 1.68-4.25) and steatosis (P = 0.002, OR = 2.29, 95% CI = 1.35-3.91), but not with necroinflammatory activity (P = 0.3). Genetic variations had only a limited impact on serum ferritin levels. CONCLUSION: In patients with CHC, elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon-alpha-based therapy. PMID- 22095910 TI - VAX1 mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: the first description of a VAX1 phenotype in humans. AB - Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, predicting p.Arg152Ser, in a proband of Egyptian origin with microphthalmia, small optic nerves, cleft lip/palate, and corpus callosum agenesis. This mutation affects an invariant residue in the homeodomain of VAX1 and was absent from 96 Egyptian controls. It is likely that the mutation results in a loss of function, as the mutation results in a phenotype similar to the Vax1 homozygous null mouse. We did not identify any mutations in VAX2. This is the first description of a phenotype associated with a VAX1 mutation in humans and establishes VAX1 as a new causative gene for A/M. PMID- 22095911 TI - The association between fracture and obesity is site-dependent: a population based study in postmenopausal women. AB - The association between obesity and fracture is controversial. We investigated the relationship between body mass index (BMI) and fracture at different skeletal sites in women aged >=50 years using data from the Sistema d' Informacio per al Desenvolupament de la Investigacio en Atencio Primaria (SIDIAP) database. SIDIAP contains the computerized medical records of >3400 general practitioners in Catalonia (northeastern Spain), with information on a representative 80% of the population (>5 million people). In 2009, 1,039,878 women aged >=50 years were eligible, of whom 832,775 (80.1%) had a BMI measurement. These were categorized into underweight/normal (302,414 women), overweight (266,798), and obese (263,563). Fractures were ascertained using the International Classification of Diseases, 10th revision (ICD-10) codes. Multivariate Poisson regression models were fitted to adjust for age, smoking, high alcohol intake, type 2 diabetes, and oral corticosteroid use. Hip fractures were significantly less common in overweight and obese women than in normal/underweight women (rate ratio [RR] 0.77 [95% confidence interval (CI) 0.68 to 0.88], RR 0.63 [95% CI 0.64 to 0.79], p < 0.001, respectively). Pelvis fracture rates were lower in the overweight (RR 0.78 [95% CI 0.63 to 0.96], p = 0.017) and obese (RR 0.58 [95% CI 0.47 to 0.73], p < 0.001) groups. Conversely, obese women were at significantly higher risk of proximal humerus fracture than the normal/underweight group (RR 1.28 [95% CI 1.04 to 1.58], p = 0.018). Clinical spine, wrist, tibial, and multiple rib fracture rates were not significantly different between groups. An age-related increase in incidence was seen for all BMI groups at all fracture sites; obese women with hip, clinical spine, and pelvis fracture were significantly younger at the time of fracture than normal/underweight women, whereas those with wrist fracture were significantly older. The association between obesity and fracture in postmenopausal women is site-dependent, obesity being protective against hip and pelvis fractures but associated with an almost 30% increase in risk for proximal humerus fractures when compared with normal/underweight women. The reasons for these site-specific variations are unknown but may be related to different patterns of falls and attenuation of their impact by adipose tissue. PMID- 22095912 TI - Green nanochemistry: metal oxide nanoparticles and porous thin films from bare metal powders. AB - A universal, simple, robust, widely applicable and cost-effective aqueous process is described for a controlled oxidative dissolution process of micrometer-sized metal powders to form high-purity aqueous dispersions of colloidally stable 3-8 nm metal oxide nanoparticles. Their utilization for making single and multilayer optically transparent high-surface-area nanoporous films is demonstrated. This facile synthesis is anticipated to find numerous applications in materials science, engineering, and nanomedicine. PMID- 22095913 TI - Detection of evolving injury to the brachial plexus during transaxillary robotic thyroidectomy. AB - OBJECTIVES/HYPOTHESIS: Continuous intraoperative neuromonitoring (IONM) of transcranial electric motor evoked potentials (tceMEPs) and somatosensory evoked potentials (SSEPs) has gained universal acceptance as an efficacious method for detecting emerging positional brachial plexopathy or peripheral nerve compression during spinal and shoulder surgery. This has implications for transaxillary thyroid surgery. STUDY DESIGN: Case report with literature review. METHODS: The patient underwent robotic transaxillary thyroid surgery with continuous tceMEP and SSEP monitoring of brachial plexus function. We present detailed IONM data depicting the emergence of positional brachial plexopathy. RESULTS: Significant amplitude loss of both IONM modalities were identified during an evolving positional plexopathy, which resolved upon upper extremity repositioning and conversion to an open procedure. No permanent nerve injury or deficit was noted following surgery. CONCLUSIONS: Given the potential for brachial plexus injury during robotic transaxillary thyroid surgery secondary to arm positioning, we recommend that continuous tceMEP and SSEP monitoring be considered during such procedures. PMID- 22095915 TI - DeltaE1 and high-capacity adenoviral vectors expressing full-length codon optimized merozoite surface protein 1 for vaccination against Plasmodium falciparum. AB - BACKGROUND: The merozoite surface protein (MSP)-1 of Plasmodium falciparum, the causative agent of malaria tropica, is considered to be a promising vaccine candidate. Although its stable cloning and expression has been difficult in the past, adenoviral vectors expressing the complex protein are described in the present study. METHODS: Codon-optimized msp-1 was used to construct a set of first generation (DeltaE1Ad) and high-capacity adenovirus (HC-Ad) vectors, and cellular and humoral immune responses induced by the vectors were characterized in detail in mice. RESULTS: Generation of stable DeltaE1Ad and HC-Ad vectors expressing full-length MSP-1 and their production to high vector titers was found to be feasible. Epitope identification and analysis of frequencies of specific CD8 T-cells revealed that MSP-1 expressing HC-Ad vectors induced higher frequencies of interferon-gamma + CD8 T-cells than DeltaE1 vectors. Irrespective of the vector format, higher titers of MSP-1 specific antibodies were generated by Ad vectors expressing MSP-1 from a chicken beta-actin (CAG) promoter comprising the cytomegalovirus early enhancer element and the chicken beta-actin promoter. CONCLUSIONS: The findings of the present study suggest that Ad vectors expressing full-length codon-optimized MSP-1 are promising candidate vaccines against P. falciparum infections. Use of the HC-Ad vector type for delivery, as well as the CAG promoter to control MSP-1 expression, may further increase the efficacy of this vaccine candidate. PMID- 22095914 TI - The giant danio (D. aequipinnatus) as a model of cardiac remodeling and regeneration. AB - The paucity of mammalian adult cardiac myocytes (CM) proliferation following myocardial infarction (MI) and the remodeling of the necrotic tissue that ensues, result in non-regenerative repair. In contrast, zebrafish (ZF) can regenerate after an apical resection or cryoinjury of the heart. There is considerable interest in models where regeneration proceeds in the presence of necrotic tissue. We have developed and characterized a cautery injury model in the giant danio (GD), a species closely related to ZF, where necrotic tissue remains part of the ventricle, yet regeneration occurs. By light and transmission electron microscopy (TEM), we have documented four temporally overlapping processes: (1) a robust inflammatory response analogous to that observed in MI, (2) concomitant proliferation of epicardial cells leading to wound closure, (3) resorption of necrotic tissue and its replacement by granulation tissue, and (4) regeneration of the myocardial tissue driven by 5-EDU and [(3) H]thymidine incorporating CMs. In conclusion, our data suggest that the GD possesses robust repair mechanisms in the ventricle and can serve as an important model of cardiac inflammation, remodeling and regeneration. PMID- 22095916 TI - Bioactivity-guided isolation of antiproliferative diterpenoids from Euphorbia kansui. AB - Cytotoxic assay guided multistep separation on the dichloromethane extract of the roots of Euphorbia kansui resulted in the isolation of 10 ingenol-type diterpenoids (1-4 and 7-12), of which, 5-O-(2'E,4'E-decadienoyl)-20-O acetylingenol (1) is a new compound, and two are jatrophane-type diterpenoids (13 14). Interconversion of two pairs of positional ester isomers (1-4) in aqueous alcoholic solution was observed, the transesterification mechanism of which was speculated and confirmed by acylation of 3 and 4 to 6 and 5, respectively. All the isolates and the two acyl derivatives (5 and 6) were evaluated in vitro for their cytotoxicities in Bel-7402, Bel-7402/5FU, BGC-823 and SGC-7901 cell lines. The 12 ingenol-type diterpenoids exhibited weak to moderate cytotoxicities, whereas the two jatrophane-type diterpenoids displayed no antiproliferative effects, which, however, may increase the antitumour efficacy of those ingenol type diterpenoids. The structure--activity relationships were investigated by principal component analysis (PCA) of the pIC50 (-logIC50) values of the compounds tested and their calculated molecular descriptors. The pIC50 values were highly correlated with most descriptors, especially the highest occupied molecular orbital energy (E(HOMO)), absolute hardness (eta) and positively charged solvent accessible surface areas (P-ASA). As the values of E(HOMO) increase, eta and P-ASA decrease, and the antiproliferative effects of these compounds increase. PMID- 22095917 TI - Project VALOR: design and methods of a longitudinal registry of post-traumatic stress disorder (PTSD) in combat-exposed veterans in the Afghanistan and Iraqi military theaters of operations. AB - Few studies have investigated the natural history of post-traumatic stress disorder (PTSD). Project VALOR (Veterans' After-discharge Longitudinal Registry) was designed as a longitudinal patient registry assessing the course of combat related PTSD among 1600 male and female Veterans who served in Operation Enduring Freedom (OEF) in Afghanistan or Operation Iraqi Freedom (OIF). Aims of the study include investigating patterns and predictors of progression or remission of PTSD and treatment utilization. The study design was based on recommendations from the Agency for Healthcare Quality and Research for longitudinal disease registries and used a pre-specified theoretical model to select the measurement domains for data collection and interpretation of forthcoming results. The registry will include 1200 male and female Veterans with a recent diagnosis of PTSD in the Department of Veteran Affairs (VA) electronic medical record and a comparison group of 400 Veterans without a medical record-based PTSD diagnosis, to also allow for case-control analyses. Data are collected from administrative databases, electronic medical records, a self-administered questionnaire, and a semi-structured diagnostic telephone interview. Project VALOR is a unique and timely registry study that will evaluate the clinical course of PTSD, psychosocial correlates, and health outcomes in a carefully selected cohort of returning OEF/OIF Veterans. PMID- 22095919 TI - Identifying continuous pores in protein structures with PROPORES by computational repositioning of gating residues. AB - Proteins containing concavities such as pockets, cavities, and tunnels or pores perform important functions in ligand-induced signal transduction, enzymatic catalysis, and in facilitating the permeation of small molecules through membranes. Computational algorithms for identifying such shapes are therefore of great use for studying the mechanisms of these reactions. We developed the novel toolkit PROPORES for pore identification and applied our program to the systems aquaporin, tryptophan synthase, leucine transporter, and acetylcholinesterase. As a novel feature, the program checks whether access to occluded ligand binding pockets or blocked channels can be achieved by systematically rotating side chains of the gating residues. In this way, we obtain a more flexible view of the putative structural adaptability of protein structures. For the four systems mentioned, the new method was able to identify connections between pores that are separated in the X-ray structures or to connect internal pores with the protein surrounding. The software is available from http://gepard.bioinformatik.uni saarland.de/software/propores/. PMID- 22095920 TI - Environmental control of reproductive phenology and the effect of pollen supplementation on resource allocation in the cleistogamous weed, Ruellia nudiflora (Acanthaceae). AB - BACKGROUND AND AIMS: Mixed reproductive strategies may have evolved as a response of plants to cope with environmental variation. One example of a mixed reproductive strategy is dimorphic cleistogamy, where a single plant produces closed, obligately self-pollinated (CL) flowers and open, potentially outcrossed (CH) flowers. Frequently, optimal environmental conditions favour production of more costly CH structures whilst economical and reliable CL structures are produced under less favourable conditions. In this study we explore (1) the effect of light and water on the reproductive phenology and (2) the effect of pollen supplementation on resource allocation to seeds in the cleistogamous weed Ruellia nudiflora. METHODS: Split-plot field experiments were carried out to assess the effect of shade (two levels: ambient light vs. a reduction of 50 %) and watering (two levels: non-watered vs. watered) on the onset, end and duration of the production of three reproductive structures: CH flowers, CH fruit and CL fruit. We also looked at the effect of these environmental factors on biomass allocation to seeds (seed weight) from obligately self-pollinated flowers (CL), open-pollinated CH flowers and pollen-supplemented CH flowers. KEY RESULTS: CH structures were produced for a briefer period and ended earlier under shaded conditions. These conditions also resulted in an earlier production of CL fruit. Shaded conditions also produced greater biomass allocation to CH seeds receiving extra pollen. CONCLUSIONS: Sub-optimal (shaded) conditions resulted in a briefer production period of CH structures whilst these same conditions resulted in an earlier production of CL structures. However, under sub-optimal conditions, plants also allocated more resources to seeds sired from CH flowers receiving large pollen loads. Earlier production of reproductive structures and relatively larger seed might improve subsequent success of CL and pollen-supplemented CH seeds, respectively. PMID- 22095921 TI - Hippocampal subregions are differentially affected in the progression to Alzheimer's disease. AB - Atrophy within the hippocampus (HP) as measured by magnetic resonance imaging (MRI) is a promising biomarker for the progression to Alzheimer's disease (AD). Subregions of the HP along the longitudinal axis have been found to demonstrate unique function, as well as undergo differential changes in the progression to AD. Little is known of relationships between such HP subregions and other potential biomarkers, such as neuropsychological (NP), genetic, and cerebral spinal fluid (CSF) beta amyloid and tau measures. The purpose of this study was to subdivide the hippocampus to determine how the head, body, and tail were affected in normal control, mild cognitively impaired, and AD subjects, and investigate relationships with HP subregions and other potential biomarkers. MRI scans of 120 participants of the Alzheimer's Disease Neuroimaging Initiative were processed using FreeSurfer, and the HP was subdivided using 3D Slicer. Each subregion was compared among groups, and correlations were used to determine relationships with NP, genetic, and CSF measures. Results suggest that HP subregions are undergoing differential atrophy in AD, and demonstrate unique relationships with NP and CSF data. Discriminant function analyses revealed that these regions, when combined with NP and CSF measures, were able to classify by diagnostic group, and classify MCI subjects who would and would not progress to AD within 12 months. PMID- 22095923 TI - Contact resistance and megahertz operation of aggressively scaled organic transistors. AB - Bottom-gate, top-contact organic thin-film transistors (TFTs) with excellent static characteristics (on/off ratio: 10(7) ; intrinsic mobility: 3 cm(2) (V s)( 1) ) and fast unipolar ring oscillators (signal delay as short as 230 ns per stage) are fabricated. The significant contribution of the transfer length to the relation between channel length, contact length, contact resistance, effective mobility, and cutoff frequency of the TFTs is theoretically and experimentally analyzed. PMID- 22095922 TI - Direct writing by way of melt electrospinning. AB - Melt electrospun fibers of poly(epsilon-caprolactone) are accurately deposited using an automated stage as the collector. Matching the translation speed of the collector to the speed of the melt electrospinning jet establishes control over the location of fiber deposition. In this sense, melt electrospinning writing can be seen to bridge the gap between solution electrospinning and direct writing additive manufacturing processes. PMID- 22095924 TI - Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications. AB - Sarcoglycanopathies (SGP) are a group of autosomal recessive muscle disorders caused by primary mutations in one of the four sarcoglycan genes. The sarcoglycans (alpha-, beta-, gamma-, and delta-sarcoglycan) form a tetrameric complex at the muscle membrane that is part of the dystrophin-glycoprotein complex and plays an essential role for membrane integrity during muscle contractions. We previously showed that the most frequent missense mutation in alpha-sarcoglycan (p.R77C) leads to the absence of the protein at the cell membrane due to its blockade by the endoplasmic reticulum (ER) quality control. Moreover, we demonstrated that inhibition of the ER alpha-mannosidase I activity using kifunensine could rescue the mutant protein localization at the cell membrane. Here, we investigate 25 additional disease-causing missense mutations in the sarcoglycan genes with respect to intracellular fate and localization rescue of the mutated proteins by kifunensine. Our studies demonstrate that, similarly to p.R77C, 22 of 25 of the selected mutations lead to defective intracellular trafficking of the SGs proteins. Six of these were saved from ER retention upon kifunensine treatment. The trafficking of SGs mutants rescued by kifunensine was associated with mutations that have moderate structural impact on the protein. PMID- 22095925 TI - High-capacity adenoviral vectors circumvent the limitations of DeltaE1 and DeltaE1/DeltaE3 adenovirus vectors to induce multispecific transgene product directed CD8 T-cell responses. AB - BACKGROUND: The ability to induce cytotoxic T lymphocyte (CTL) responses that are multispecific is considered to comprise an essential feature for an efficacious genetic vaccine against many pathogens including HIV and hepatitis C virus. DeltaE1Ad vectors are promising vectored vaccines but have been shown to induce antigen-specific CTLs with only limited multispecificity. In the present study, we investigated the applicability of gene-deleted high-capacity adenovirus (HC Ad) vectors and focused on the induction of multispecific CTL responses. METHODS: We generated Delta E1 and HC-Ad vectors expressing hepatitis B virus small surface antigen (HBsAg). We comparatively analyzed the CTL profiles against various transgene product- and vector-derived epitopes in several mouse strains and HBsAg- and vector-directed antibody responses. RESULTS: HC-Ad vectors efficiently induced multispecific HBsAg-directed CTLs. By contrast, DeltaE1Ad vectors mainly primed CTLs against one immunodominant epitope of HBsAg. This absence of multispecific CTL responses correlated with the induction of CTLs against viral epitopes generated by de novo expression of Ad genes from the DeltaE1Ad vector. However, Ad-specific CTLs induced in trans did not impair HC AdS-induced multispecific CTL responses against HBsAg. Finally, HC-Ad vectors also induced higher HBsAg antibody titers compared to DeltaE1Ad vectors. CONCLUSIONS: De novo expression of viral genes from DeltaE1Ad vector genomes restricts the multispecificity of transgene product-specific CTLs by immunodominance effects. HC-Ad vectors devoid of Ad genes are favorable for the induction of both multispecific CD8 T-cell responses and high antibody responses. Our results suggest the deletion of Ad genes as an important means for developing potent Ad-based vectored vaccines. PMID- 22095926 TI - Crystal structure of methylornithine synthase (PylB): insights into the pyrrolysine biosynthesis. PMID- 22095927 TI - Antidiabetic effect of the total polyphenolic acids fraction from Salvia miltiorrhiza Bunge in diabetic rats. AB - An investigation was made to evaluate the therapeutic potential of the total polyphenolic acids fraction (PAF) from Salvia miltiorrhiza Bunge in the type 2 diabetes mellitus rats model with an oral dose of 187 mg/kg for 28 days. The results showed that PAF induced a significant decrease in fasting blood glucose (FBG), fasting blood insulin (FINS), total cholesterol (TC), triglyceride (TG) and blood urea nitrogen (BUN), and an obvious increase in insulin sensitivity index (ISI) in diabetic rats induced by a high fat diet and a low dose of streptozocin (STZ). These results suggested that PAF has antidiabetic potential in vivo. PMID- 22095928 TI - The basics of retinoblastoma: back to school. PMID- 22095929 TI - Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study. AB - BACKGROUND: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services, health experience, social outcomes, and lifestyle behavior of AML survivors with that of their sibling controls. METHODS: This population-based study included 138 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, and alive by June 30, 2007. Patients treated with hematopoietic stem cell transplantation (HSCT) or relapse were not included. Altogether, 102 (74%) survivors and 91% of their siblings completed a questionnaire. RESULTS: The median follow-up was 11 (range 4-25) years after diagnosis. AML survivors had no increased rate of hospitalization compared with sibling controls, but were more often receiving prescription drugs, especially for asthma (23% vs. 9%, P = 0.03). Self-reported health experience was excellent or very good in 77% and comparable with that of siblings. Educational achievement, employment, and marital status were comparable in the two groups. Among surviving AML patients, 23% were current smokers and 24% of their siblings were current smokers. CONCLUSIONS: The self-reported health of children treated on NOPHO-AML protocols without HSCT was good, and their use of health care services was limited. Reported health and social outcomes were comparable to those of their siblings. Many survivors were smoking which may increase the risk of late effects. PMID- 22095930 TI - Differential expression and regulation of angiopoietin-2 in mouse uterus during preimplantation period. AB - Angiogenesis is crucial to successful implantation and decidualization, however, as an important angiogenic growth factor, the effect of Ang-2 in the process of implantation and decidualization is still unknown. This study is to investigate the differential expression of Ang-2 in mouse uterus during early pregnancy and its regulation by steroid hormones using in situ hybridization and RT-PCR. There is no detectable Ang-2 mRNA signal on days 1-5 of pregnancy by in situ hybridization. On days 6-8, Ang-2 mRNA is mainly expressed in the primary decidua of mesometrial side, and the expression gradually increases. By RT-PCR, a significantly higher level of Ang-2 expression is observed on day 8 of pregnancy, although Ang-2 expression can be found through days 1-8. Similarly, Ang-2 is highly expressed in decidualized cells under artificial decidualization. In the ovariectomized mouse uterus, Ang-2 expression gradually increases after estrogen injection and with peak levels at 12 hr, while progesterone injection can cause a decline in uterine Ang-2 mRNA level, which reaches a nadir at 12 hr. These results suggest that Ang-2 may play a key role in the process of mouse decidualization. Estrogen can induce the expression of Ang-2 while progesterone can inhibit its expression in the ovariectomized mouse uterus. PMID- 22095931 TI - In vivo NIR fluorescence imaging, biodistribution, and toxicology of photoluminescent carbon dots produced from carbon nanotubes and graphite. AB - Oxidization of carbon nanotubes by a mixed acid has been utilized as a standard method to functionalize carbon nanomaterials for years. Here, the products obtained from carbon nanotubes and graphite after a mixed-acid treatment are carefully studied. Nearly identical carbon dot (Cdot) products with diameters of 3-4 nm are produced using this approach from a variety of carbon starting materials, including single-walled carbon nanotubes, multiwalled carbon nanotubes, and graphite. These Cdots exhibit strong yellow fluorescence under UV irradiation and shifted emission peaks as the excitation wavelength is changed. In vivo fluorescence imaging with Cdots is then demonstrated in mouse experiments, by using varied excitation wavelengths including some in the near infrared (NIR) region. Furthermore, in vivo biodistribution and toxicology of those Cdots in mice over different periods of time are studied; no noticeable signs of toxicity for Cdots to the treated animals are discovered. This work provides a facile method to synthesize Cdots as safe non-heavy-metal-containing fluorescent nanoprobes, promising for applications in biomedical imaging. PMID- 22095932 TI - Magnetic nanocarriers with tunable pH dependence for controlled loading and release of cationic and anionic payloads. AB - Superparamagnetic nanocarriers with tunable pH dependence of the surface charge are designed by a simple co-precipitation method. By exploiting electrostatic interactions, cationic or anionic payloads can be adsorbed and desorbed depending on the pH. On three different resulting nanocarrier systems, experiments of loading and release of gold nanoparticles as well as effective siRNA loading and in vitro delivery on human cells are performed. PMID- 22095933 TI - Detection of liver metastases using gadoxetic-enhanced dynamic and 10- and 20 minute delayed phase MR imaging. AB - PURPOSE: To assess the incremental value of hepatobiliary phase images in gadoxetate disodium-enhanced magnetic resonance imaging (MRI), and to compare diagnostic accuracy and lesion conspicuity on 10- and 20-minute delayed images for preoperative detection of hepatic metastases with subgroup analysis according to size and history of chemotherapy. MATERIALS AND METHODS: Forty-six patients with 107 metastases who underwent surgery after gadoxetate disodium-enhanced MRI were evaluated. Four observers independently interpreted three sets: dynamic set comprising precontrast T1-, T2-weighted, and dynamic images; 10-minute set comprising dynamic set and 10-minute delayed; 20-minute set comprising 10-minute set and 20-minute delayed. Diagnostic accuracy was compared with subgroup analysis. Liver-to-lesion signal ratio (SR) was calculated using the region of interest method and compared. RESULTS: Mean A(z) and sensitivities were significantly higher for 10- (A(z) = 0.894, sensitivity = 95.6%) and 20-minute (0.910, 97.2%) than dynamic set (0.813, 79.9%) (P < 0.001), with no significant difference between 10- and 20-minute sets (P = 0.140). In patients with small (<=1 cm) metastases and a history of chemotherapy, sensitivities were significantly higher with 10- (88.2%) and 20-minute (91.6%) sets than dynamic set (48.6%) (P < 0.001). SR was significantly higher for 10- and 20-minute delayed than precontrast and dynamic, with significantly higher SR on 20- than 10-minute delayed. CONCLUSION: Regardless of size or prior chemotherapy, detection of hepatic metastases was significantly improved by adding hepatobiliary phase images without significant differences between 10- and 20-minute delayed. PMID- 22095934 TI - The future of physiotherapy education: towards a translational model of learning complex skills. PMID- 22095935 TI - Genetic variation in APOB, PCSK9, and ANGPTL3 in carriers of pathogenic autosomal dominant hypercholesterolemic mutations with unexpected low LDL-Cl Levels. AB - Autosomal Dominant Hypercholesterolemia (ADH) is caused by LDLR and APOB mutations. However, genetically diagnosed ADH patients do not always exhibit the expected hypercholesterolemic phenotype. Of 4,669 genetically diagnosed ADH patients, identified through the national identification screening program for ADH, 75 patients (1.6%) had LDL-cholesterol (LDL-C) levels below the 50th percentile for age and gender prior to lipid-lowering therapy. The genes encoding APOB, PCSK9, and ANGPTL3 were sequenced in these subjects to address whether monogenic dominant loss-of-function mutations underlie this paradoxical phenotype. APOB mutations, resulting in truncated APOB, were found in five (6.7%) probands, reducing LDL-C by 56%. Rare variants in PCSK9, and ANGPTL3 completely correcting the hypercholesterolemic phenotype were not found. The common variants p.N902N, c.3842+82T>A, p.D2312D, and p.E4181K in APOB, and c.1863+94A>G in PCSK9 were significantly more prevalent in our cohort compared to the general European population. Interestingly, 40% of our probands carried at least one minor allele for all four common APOB variants compared to 1.5% in the general European population. While we found a low prevalence of rare variants in our cohort, our data suggest that regions in proximity of the analyzed loci, and linked to specific common haplotypes, might harbor additional variants that correct an ADH phenotype. PMID- 22095936 TI - Convex polyhedral Au@Pd core-shell nanocrystals with high-index facets. PMID- 22095937 TI - A review of the efficacy and safety of banaba (Lagerstroemia speciosa L.) and corosolic acid. AB - Banaba (Lagerstroemia speciosa L.) extracts have been used for many years in folk medicine to treat diabetes, with the first published research study being reported in 1940. This review summarizes the current literature regarding banaba and its constituents. The hypoglycemic effects of banaba have been attributed to both corosolic acid as well as ellagitannins. Studies have been conducted in various animal models, human subjects and in vitro systems using water soluble banaba leaf extracts, corosolic acid-standardized extracts, and purified corosolic acid and ellagitannins. Pure corosolic acid has been reported to decrease blood sugar levels within 60 min in human subjects. Corosolic acid also exhibits antihyperlipidemic, antioxidant, antiinflammatory, antifungal, antiviral, antineoplastic and osteoblastic activities. The beneficial effects of banaba and corosolic acid with respect to various aspects of glucose and lipid metabolism appear to involve multiple mechanisms, including enhanced cellular uptake of glucose, impaired hydrolysis of sucrose and starches, decreased gluconeogenesis and the regulation of lipid metabolism. These effects may be mediated by PPAR, MAP K, NF-kappaB and other signal transduction factors. No adverse effects have been observed or reported in animal studies or controlled human clinical trials. Banaba extract, corosolic acid and other constituents may be beneficial in addressing the symptoms associated with metabolic syndrome, as well as offering other health benefits. PMID- 22095938 TI - Histology-based morphology of the neurocentral synchondrosis in Alligator mississippiensis (Archosauria, Crocodylia). AB - Morphology of the neurocentral synchondroses--thin cartilaginous layers between centra and neural arches--are documented in the extant crocodilian, Alligator mississippiensis (Archosauria, Crocodylia). Examination of dry skeletons demonstrates that neurocentral suture closure occurs in very late postnatal ontogeny (after reaching sexual maturity and/or body size ca. 40% from the upper range). Before sexual maturity (body length (BL) >= ca. 1.80 m), completely fused centra and neural arches are restricted to the caudal vertebral series. In contrast, the presacral vertebrae often remain unfused throughout postnatal ontogeny, retaining open sutures in very mature individuals (BL >= 2.80 m). These unfused centra and neural arches are structurally supported by the relatively large surface area of the neurocentral junctions, which results from primarily horizontal (mediolateral) increases with strong positive allometry. Cleared and stained specimens show that the cartilaginous neurocentral synchondrosis starts to form after approximately 40 embryonic days. Histological examination of the neurocentral junction in dorsal and anterior caudal vertebrae of six individuals (BL = 0.28-3.12 m) shows : (1) neurocentral fusion is the result of endochondral ossification of the neurocentral synchondrosis, (2) the neurocentral synchondrosis exhibits bipolar organization of three types of cartilaginous cells, and (3) complex neurocentral sutures (i.e., curved, zigzagged, and/or interdigitated boundaries) come from clumping of bone cells of the neural arches and centra into the neurocentral synchondrosis. The last two morphological features can be advantageous for delaying neurocentral fusion, which seems to be unique in crocodilians and possibly their close relatives, including nonavian dinosaurs and other Mesozoic archosaurs. PMID- 22095939 TI - Electrical probing of submicroliter liquid using graphene strip transistors built on a nanopipette. AB - Graphene sheets made by chemical vapor deposition are transferred onto a glass nanopipette to form graphene strips. Two strips are connected at the nanopipette tip end to form a transistor channel. This graphene-based transistor can be operated in a liquid-gating condition, thereby allowing the electrical detection of the pH value of a droplet with submicroliter volume. PMID- 22095940 TI - Organic mixed-valence compounds: a playground for electrons and holes. AB - Mixed-valence (MV) compounds are excellent model systems for the investigation of basic electron-transfer (ET) or charge-transfer (CT) phenomena. These issues are important in complex biophysical processes such as photosynthesis as well as in artificial electronic devices that are based on organic conjugated materials. Organic MV compounds are effective hole-transporting materials in organic light emitting diodes (OLEDs), solar cells, and photochromic windows. However, the importance of organic mixed-valence chemistry should not be seen in terms of the direct applicability of these species but the wealth of knowledge about ET phenomena that has been gained through their study. The great variety of organic redox centers and spacer moieties that may be combined in MV systems as well as the ongoing refinement of ET theories and methods of investigation prompted enormous interest in organic MV compounds in the last decades and show the huge potential of this class of compounds. The goal of this Review is to give an overview of the last decade in organic mixed valence chemistry and to elucidate its impact on modern functional materials chemistry. PMID- 22095941 TI - Impact of parainfluenza virus infection in pediatric cancer patients. AB - BACKGROUND: Respiratory virus (RV) infection can cause significant morbidity and mortality in pediatric cancer patients. Parainfluenza virus (PIV) is a common pathogen in childhood among the respiratory viruses. The objective of this study is to evaluate the impact of parainfluenza virus infection in pediatric cancer patients. PROCEDURE: A retrospective review of medical records of 1,554 children diagnosed with cancer from January 2000 through July 2008 was analyzed at Samsung Medical Center. RESULTS: A total of 6.4% (137/1,554) had respiratory virus infection and 54% (74/137) of patients with RV infection had PIV infection. PIV type 3 was the predominant subtype. Among patients with PIV infection, 59 children (79.7%) had upper respiratory tract infection (URI) whereas 15 children (20.3%) had lower respiratory tract infection (LRI) at initial presentation. Among patients with URI, 12 (20.3%) progressed to pneumonia with the median interval of 4 days from URI to LRI. Mortality associated with PIV infection was 18.5% (5/27) in patients with LRI. Among patients with PIV infection, 80% (59/74) had nosocomial infection, which shows the difficulty and importance of infection control at pediatric cancer ward. CONCLUSIONS: PIV infection was most commonly diagnosed among pediatric cancer patients with RV infection and PIV infection led to significant pulmonary complications and direct mortality in immunocompromised children. Since there are no effective antiviral agents for PIV infection, precautionary infection control and early diagnosis are the only methods available to prevent the infection spread. PMID- 22095942 TI - Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis. AB - Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two-thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS in the maintenance of blood pressure and renal blood flow during the life of a human fetus. Renal hypoperfusion, whether genetic or secondary to a variety of diseases, precludes the normal development/ differentiation of proximal tubules. The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis. PMID- 22095943 TI - Urinary FSP1 is a biomarker of crescentic GN. AB - Fibroblast-specific protein 1 (FSP1)-expressing cells accumulate in damaged kidneys, but whether urinary FSP1 could serve as a biomarker of active renal injury is unknown. We measured urinary FSP1 in 147 patients with various types of glomerular disease using ELISA. Patients with crescentic GN, with or without antinuclear cytoplasmic antibody-associated GN, exhibited elevated levels of urinary FSP1. This assay had a sensitivity of 91.7% and a specificity of 90.2% for crescentic GN in this sample of patients. Moreover, we found that urinary FSP1 became undetectable after successful treatment, suggesting the possible use of FSP1 levels to monitor disease activity over time. Urinary FSP1 levels correlated positively with the number of FSP1-positive glomerular cells, predominantly podocytes and cellular crescents, the likely source of urinary FSP1. Even in patients without crescent formation, patients with high levels of urinary FSP1 had large numbers of FSP1-positive podocytes. Taken together, these data suggest the potential use of urinary FSP1 to screen for active and ongoing glomerular damage, such as the formation of cellular crescents. PMID- 22095944 TI - Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis. AB - Synthesis and deposition of extracellular matrix (ECM) within the glomerulus and interstitium characterizes renal fibrosis, but the mechanisms underlying this process are incompletely understood. The profibrotic cytokine TGF-beta1 modulates the expression of certain microRNAs (miRNAs), suggesting that miRNAs may have a role in the pathogenesis of renal fibrosis. Here, we exposed proximal tubular cells, primary mesangial cells, and podocytes to TGF-beta1 to examine its effect on miRNAs and subsequent collagen synthesis. TGF-beta1 reduced expression of the miR-29a/b/c/family, which targets collagen gene expression, and increased expression of ECM proteins. In both resting and TGF-beta1-treated cells, ectopic expression of miR-29 repressed the expression of collagens I and IV at both the mRNA and protein levels by targeting the 3'untranslated region of these genes. Furthermore, we observed low levels of miR-29 in three models of renal fibrosis representing early and advanced stages of disease. Administration of the Rho associated kinase inhibitor fasudil prevented renal fibrosis and restored expression of miR-29. Taken together, these data suggest that TGF-beta1 inhibits expression of the miR-29 family, thereby promoting expression of ECM components. Pharmacologic modulation of these miRNAs may have therapeutic potential for progressive renal fibrosis. PMID- 22095945 TI - Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody associated glomerulonephritis after rituximab therapy. AB - Histopathological features in renal biopsies of patients with antineutrophil cytoplasmic antibody-associated vasculitis have predictive value for renal outcome in patients who receive standard treatment with cyclophosphamide and corticosteroids; however, whether the same holds true for rituximab-treated patients is unknown. We describe associations between renal histopathology and outcomes among patients treated with a rituximab-based regimen in the Randomized Trial of Rituximab versus Cyclophosphamide in ANCA-Associated Vasculitis trial. Two pathologists, blinded to clinical data, reviewed biopsies from 30 patients according to a standardized protocol that included assessment of T cell, B cell, and plasma cell infiltration, as well as scoring for tubulitis, interstitial inflammation, and glomerulitis. We did not observe associations between immunohistology scores and age, sex, estimated GFR at entry, or requirement for dialysis. However, tubulointerstitial inflammation was more severe among patients who had a positive test for the myeloperoxidase antineutrophil cytoplasmic antibody. In a multiple linear regression model, both CD3(+) T cell tubulitis and tubular atrophy independently associated with estimated GFR at 12 months. Tubular atrophy remained an independent predictor at 24 months (P<0.01). These results suggest that in addition to anti-B cell therapy, therapy directed at T cells may improve renal outcomes in antineutrophil cytoplasmic antibody-associated vasculitis. PMID- 22095946 TI - Mannose receptor 2 attenuates renal fibrosis. AB - Mannose receptor 2 (Mrc2) expresses an extracellular fibronectin type II domain that binds to and internalizes collagen, suggesting that it may play a role in modulating renal fibrosis. Here, we found that Mrc2 levels were very low in normal kidneys but subsets of interstitial myofibroblasts and macrophages upregulated Mrc2 after unilateral ureteral obstruction (UUO). Renal fibrosis and renal parenchymal damage were significantly worse in Mrc2-deficient mice. Similarly, Mrc2-deficient Col4alpha3(-/-) mice with hereditary nephritis had significantly higher levels of total kidney collagen, serum BUN, and urinary protein than Mrc2-sufficient Col4alpha3(-/-) mice. The more severe phenotype seemed to be the result of reduced collagen turnover, because procollagen III (alpha1) mRNA levels and fractional collagen synthesis in the wild-type and Mrc2 deficient kidneys were similar after UUO. Although Mrc2 associates with the urokinase receptor, differences in renal urokinase activity did not account for the increased fibrosis in the Mrc2-deficient mice. Treating wild-type mice with a cathepsin inhibitor, which blocks proteases implicated in Mrc2-mediated collagen degradation, worsened UUO-induced renal fibrosis. Cathepsin mRNA profiles were similar in Mrc2-positive fibroblasts and macrophages, and Mrc2 genotype did not alter relative cathepsin mRNA levels. Taken together, these data establish an important fibrosis-attenuating role for Mrc2-expressing renal interstitial cells and suggest the involvement of a lysosomal collagen turnover pathway. PMID- 22095947 TI - Matrix metalloproteinase-7 as a surrogate marker predicts renal Wnt/beta-catenin activity in CKD. AB - A variety of chronic kidney diseases exhibit reactivation of Wnt/beta-catenin signaling. In some tissues, beta-catenin transcriptionally regulates matrix metalloproteinase-7 (MMP-7), but the association between MMP-7 and Wnt/beta catenin signaling in chronic kidney disease is unknown. Here, in mouse models of both obstructive nephropathy and focal segmental glomerulosclerosis (adriamycin nephropathy), we observed upregulation of MMP-7 mRNA and protein in a time dependent manner. The pattern and extent of MMP-7 induction were positively associated with Wnt/beta-catenin signaling in these models. Activation of beta catenin through ectopic expression of Wnt1 promoted MMP-7 expression in vivo, whereas delivery of the gene encoding the endogenous Wnt antagonist Dickkopf-1 abolished its induction. Levels of MMP-7 protein detected in the urine correlated with renal Wnt/beta-catenin activity. Pharmacologic blockade of Wnt/beta-catenin signaling by paricalcitol inhibited MMP-7 expression in diseased kidneys and reduced the levels detected in the urine. In vitro, beta-catenin activation induced the expression and secretion of MMP-7 and promoted the binding of T cell factor to the MMP-7 promoter in kidney epithelial cells. We also observed higher levels of MMP-7 expression, which correlated with beta-catenin, in kidney tissue from patients with various nephropathies. In summary, levels of renal MMP-7 correlate with Wnt/beta-catenin activity, and urinary MMP-7 may be a noninvasive biomarker of this profibrotic signaling in the kidney. PMID- 22095948 TI - Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury. AB - The concentration of urine influences the concentration of urinary biomarkers of AKI. Whether normalization to urinary creatinine concentration, as commonly performed to quantitate albuminuria, is the best method to account for variations in urinary biomarker concentration among patients in the intensive care unit is unknown. Here, we compared the diagnostic and prognostic performance of three methods of biomarker quantitation: absolute concentration, biomarker normalized to urinary creatinine concentration, and biomarker excretion rate. We measured urinary concentrations of alkaline phosphatase, gamma-glutamyl transpeptidase, cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and IL-18 in 528 patients on admission and after 12 and 24 hours. Absolute concentration best diagnosed AKI on admission, but normalized concentrations best predicted death, dialysis, or subsequent development of AKI. Excretion rate on admission did not diagnose or predict outcomes better than either absolute or normalized concentration. Estimated 24-hour biomarker excretion associated with AKI severity, and for neutrophil gelatinase-associated lipocalin and cystatin C, with poorer survival. In summary, normalization to urinary creatinine concentration improves the prediction of incipient AKI and outcome but provides no advantage in diagnosing established AKI. The ideal method for quantitating biomarkers of urinary AKI depends on the outcome of interest. PMID- 22095949 TI - EGFR signaling promotes TGFbeta-dependent renal fibrosis. AB - The mechanisms by which angiotensin II (Ang II) promotes renal fibrosis remain incompletely understood. Ang II both stimulates TGFbeta signaling and activates the EGF receptor (EGFR), but the relative contribution of these pathways to renal fibrogenesis is unknown. Using a murine model with EGFR-deficient proximal tubules, we demonstrate that upstream activation of EGFR-dependent ERK signaling is critical for mediating sustained TGFbeta expression in renal fibrosis. Persistent activation of the Ang II receptor stimulated ROS-dependent phosphorylation of Src, leading to sustained EGFR-dependent signaling for TGFbeta expression. Either genetic or pharmacologic inhibition of EGFR significantly decreased TGFbeta-mediated fibrogenesis. We conclude that TGFbeta-mediated tissue fibrosis relies on a persistent feed-forward mechanism of EGFR/ERK activation through an unexpected signaling pathway, highlighting EGFR as a potential therapeutic target for modulating tissue fibrogenesis. PMID- 22095951 TI - Embryonic liver morphology and morphometry by magnetic resonance microscopic imaging. AB - Embryonic liver has a unique external morphology and quantitative morphometry, based on magnetic resonance imaging data of human embryos from the Kyoto Collection of Human Embryos. Liver morphogenesis is strongly affected by the adjacent organs and tissues. The left ventricle develops to the left medial caudal side, which results in the formation of a depression at left medial region and a prominence bilaterally at the cranial surface of the liver between Carnegie Stage (CS)17 and CS19. An imprint of the stomach that formed at the dorsal left medial region of the liver became more marked with development until CS23. A depression induced by the umbilicus formed at the ventral region of the liver between CS16 and CS19. An indentation caused by the right adrenal gland formed at the dorsal-caudal region of the liver surface from CS20. Morphometric analysis revealed that the volume of the liver increased exponentially from CS14 through CS23. The liver developed preferentially along the dorsoventral axis and right/left axis until CS17, along the craniocaudal axis between CS17 and CS19, and then in all directions after CS19. Several important developmental phenomena, such as differentiation of the diaphragm, the extension of the body axis of the embryo, and the physiologic herniation of the intestine into the umbilical cord, may affect morphometric data. These data contribute to a better understanding of liver development as well as the morphogenesis of adjacent organs, both temporally and spatially, and serve as a useful reference for fetal medicine and prenatal diagnosis. PMID- 22095950 TI - Inhibition of sphingosine 1-phosphate receptor 2 protects against renal ischemia reperfusion injury. AB - Activation of the sphingosine 1-phosphate receptor 1 (S1P(1)R) protects against renal ischemia-reperfusion (IR) injury and inflammation, but the role of other members of this receptor family in modulating renal IR injury is unknown. We found that a selective S1P(2)R antagonist protected against renal IR injury in a dose-dependent manner. Consistent with this observation, both S1P(2)R-deficient mice and wild-type mice treated with S1P(2)R small interfering RNA had reduced renal injury after IR. In contrast, a selective S1P(2)R agonist exacerbated renal IR injury. The S1P(2)R antagonist increased sphingosine kinase-1 (SK1) expression via Rho kinase signaling in renal proximal tubules; the S1P(2)R agonist decreased SK1. S1P(2)R antagonism failed to protect the kidneys of SK1-deficient mice or wild-type mice pretreated with an SK1 inhibitor or an S1P(1)R antagonist, suggesting that the renoprotection conferred by S1P(2)R antagonism results from pathways involving activation of S1P(1)R by SK1. In cultured human proximal tubule (HK-2) cells, the S1P(2)R antagonist selectively upregulated SK1 and attenuated both H(2)O(2)-induced necrosis and TNF-alpha/cycloheximide-induced apoptosis; the S1P(2)R agonist had the opposite effects. In addition, increased nuclear hypoxia inducible factor-1alpha was critical in mediating the renoprotective effects of S1P(2)R inhibition. Finally, induction of SK1 and S1P(2)R in response to renal IR and S1P(2)R antagonism occurred selectively in renal proximal tubule cells but not in renal endothelial cells. Taken together, these data suggest that S1P(2)R may be a therapeutic target to attenuate the effects of renal IR injury. PMID- 22095952 TI - The otolaryngologist's cost in treating facial trauma: American Academy of Otolaryngology--Head and Neck Surgery survey. AB - OBJECTIVES: (1) To define practice patterns and perceptions of junior otolaryngologists treating maxillofacial/neck trauma. (2) To identify manners in which the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) can meet future trauma needs. STUDY DESIGN: Cross-sectional survey. SETTING: Academic and private otolaryngology practices. METHODS: A 26-question survey was designed to identify demographics, practice patterns, perceptions, and areas for improvement in maxillofacial/neck trauma care. It was distributed anonymously to AAO-HNS members completing residency from 2005 to 2009. Analysis included descriptive statistics and chi(2) comparisons. RESULTS: Of 1343 otolaryngologists, 444 (33%) responded. A total of 85% of responding physicians treat maxillofacial/neck trauma, and 64% identify trauma as an ideal part of their practice. Sense of duty (54%), institutional requirements (33%), and enjoyment (32%) are the most common reasons for treating trauma. Major deterrents include patient noncompliance (60%) and lifestyle limitations (47%). Five respondents (3.1%) have been involved in a trauma-related lawsuit. While insufficient reimbursement is a major deterrent to treating trauma (52%), only 36% would increase their volume if reimbursement improved. Increased educational opportunities represent the most common request to the AAO-HNS (59%), followed by AAO-HNS focus on improved reimbursement and tort reform (28%). CONCLUSION: Most junior otolaryngologists treat maxillofacial/neck trauma on a monthly basis. A total of 64% identify trauma as a component of their ideal practice. They report being well to very well trained in all facets of trauma, with the exception of vascular and laryngotracheal injuries; but they desire additional education, such as courses and panels. Universal concerns include inadequate reimbursement, limited pool of treating physicians, and lack of practice guidelines. PMID- 22095953 TI - Myxoid neurothekeoma of the caudal nasal septum and tip. PMID- 22095954 TI - Polysomnography before tonsillectomy in children: who and when? AB - The diagnosis of sleep-disordered breathing in children has centered around polysomnography (PSG). While PSG is considered the gold standard for diagnosis of obstructive sleep apnea in children, the need for PSG before adenotonsillectomy is widely debated. An evidence-based clinical practice guideline on the use of PSG in children before tonsillectomy has recently been published. The recommendations contained in this guideline are discussed, emphasizing the appropriate indications for PSG as well as the limitations of existing evidence for the use of PSG and diagnosis of sleep-disordered breathing in children. PMID- 22095955 TI - Aspirin analogues as dual cyclooxygenase-2/5-lipoxygenase inhibitors: synthesis, nitric oxide release, molecular modeling, and biological evaluation as anti inflammatory agents. AB - Analogues of aspirin were synthesized through an efficient one-step reaction in which the carboxyl group was replaced by an ethyl ester, and/or the acetoxy group was replaced by an N-substituted sulfonamide (SO(2)NHOR(2):R(2) =H, Me, CH(2)Ph) pharmacophore. These analogues were designed for evaluation as dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors. In vitro COX 1/COX-2 isozyme inhibition studies identified compounds 11 (CO(2) H, SO(2)NHOH), 12 (CO(2)H, SO(2)NHOCH(2)Ph), and 16 (CO(2)Et, SO(2)NHOH) as highly potent and selective COX-2 inhibitors (IC(50) range: 0.07-0.7 MUM), which exhibited appreciable in vivo anti-inflammatory activity (ED(50) range: 23.1-31.4 mg kg( 1)). Moreover, compounds 11 (IC(50) =0.2 MUM) and 16 (IC(50) =0.3 MUM), with a sulfohydroxamic acid (SO(2)NHOH) moiety showed potent 5-LOX inhibitory activity. Furthermore, the SO(2)NHOH moiety present in compounds 11 and 16 was found to be a good nitric oxide (NO) donor upon incubation in phosphate buffer at pH 7.4. Molecular docking studies in the active binding site of COX-2 and 5-LOX provided complementary theoretical support for the experimental biological structure activity data acquired. PMID- 22095956 TI - Remarkable stability and cytostatic effect of a quercetin conjugate, 3,7-bis-O pivaloxymethyl (POM) quercetin. PMID- 22095957 TI - Effect of the WISH-type hip brace on functional mobility in patients with osteoarthritis of the hip: evaluation using the Timed Up & Go Test. AB - BACKGROUND: The WISH-type S-form brace, is considered to improve hip function and gait in patients presenting with painful hip osteoarthritis (OA). OBJECTIVES: To evaluate the effects of the brace on functional mobility. STUDY DESIGN: Cross sectional survey. METHODS: The Timed Up & Go Test (TUG) was performed with right and left turns separately in each subject. RESULTS: In the patients with the bilateral hip brace, the average time to complete the TUG (8.3 +/- 1.7 seconds) was significantly shorter than in those without the brace (9.4 +/- 2.9 seconds). On the other hand, for the patients with unilateral hip OA, the improvement of TUG with the hip brace was significant in turning the unbraced leg inside (7.4 +/ 1.1 vs. 7.6 +/- 1.2 seconds), while not turning the braced leg inside (7.5 +/- 1.1 vs. 7.6 +/- 1.2 seconds). Furthermore, significant improvement of TUG was found at three-month follow-up and maintained until the 12-month follow-up assessment. This improvement was independent of the application of the brace at the assessment. CONCLUSIONS: The direct effect of the hip brace may be related to the hip function in the turning phase of TUG. In addition, mechanical improvements due to daily exercise may provide an indirect, but essential, effect of the brace on TUG performance. PMID- 22095958 TI - PET imaging of glutaminolysis in tumors by 18F-(2S,4R)4-fluoroglutamine. AB - Changes in gene expression, metabolism, and energy requirements are hallmarks of cancer growth and self-sufficiency. Upregulation of the PI3K/Akt/mTor pathway in tumor cells has been shown to stimulate aerobic glycolysis, which has enabled (18)F-FDG PET tumor imaging. However, of the millions of (18)F-FDG PET scans conducted per year, a significant number of malignant tumors are (18)F-FDG PET negative. Recent studies suggest that several tumors may use glutamine as the key nutrient for survival. As an alternative metabolic tracer for tumors, (18)F (2S,4R)4-fluoroglutamine was developed as a PET tracer for mapping glutaminolytic tumors. METHODS: A series of in vitro cell uptake and in vivo animal studies were performed to demonstrate tumor cell addiction to glutamine. Cell uptake studies of this tracer were performed in SF188 and 9L glioblastoma tumor cells. Dynamic small-animal PET studies of (18)F-(2S,4R)4-fluoroglutamine were conducted in 2 animal models: xenografts produced in F344 rats by subcutaneous injection of 9L tumor cells and transgenic mice with M/tomND spontaneous mammary gland tumors. RESULTS: In vitro studies showed that both transformed 9L and SF188 tumor cells displayed a high rate of glutamine uptake (maximum uptake, ~ 16% dose/100 MUg of protein). The cell uptake of (18)F-(2S,4R)4-fluoroglutamine by SF188 cells is comparable to that of (3)H-L-glutamine but higher than that of (18)F-FDG. The tumor cell uptake can be selectively blocked. Biodistribution and PET studies showed that (18)F-(2S,4R)4-fluoroglutamine localized in tumors with a higher uptake than in surrounding muscle and liver tissues. Data suggest that certain tumor cells may use glutamine for energy production. CONCLUSION: The results support that (18)F-(2S,4R)4-fluoroglutamine is selectively taken up and trapped by tumor cells. It may be useful as a novel metabolic tracer for tumor imaging. PMID- 22095959 TI - Synthesis of self-threading bithiophenes and their structure-property relationships regarding cyclic side-chains with atomic precision. AB - We have recently reported a self-threading polythiophene as a new family of insulated molecular wires. Herein, we focused on the structure-property relationships of the unique three-dimensional architecture of the monomer. We have synthesized nine self-threading bithiophene monomers that have cyclic side chains of different size and flexibility: i.e., 21-, 22-, 23-, 24-, 26-, and 30 membered rings composed of paraffinic, olefinic, or alkynic chains. To investigate their structure-property relationships, (1) H NMR spectroscopy, UV absorption, and fluorescence spectroscopy measurements were conducted. We found that cyclic side-chains define the movable range of the dihedral angle of the bithiophene backbone, thereby affecting its photophysical properties. Therefore, the ability to design a structure with atomic precision as described herein would lead to the fine-tuning of the electronic properties of insulated molecular wires. PMID- 22095960 TI - Is the Wingspan stent more dangerous than natural history in intracranial stenosis? PMID- 22095962 TI - Significant volume reduction and shape abnormalities of the basal ganglia in cases of chronic liver cirrhosis. AB - BACKGROUND AND PURPOSE: Chronic liver disease frequently includes cognitive and movement disorders, suggesting an alteration of the striatum. With the exception of hyperintensities evident on T1-weighted images indicative of Mn deposition, radiographic findings of the BG are nonspecific. Volumetric and morphometric analysis of DGM is limited. Whether DGM undergoes degeneration and whether this change is associated with pallidal hyperintensity and cognitive performance are currently unknown in patients with cirrhosis. MATERIALS AND METHODS: The DGM volumes of 28 patients with chronic cirrhosis and 28 control patients were compared. Using 3D high-resolution MR images, the volume and shape of each structure were automatically analyzed by the FSL. Correlations between the DGM volume and other clinical variables, including the pallidal signal intensity, were assessed by multiple regression analysis. RESULTS: Patients with Child B and Child C liver disease had significantly smaller bilateral putaminal volumes than control patients, and patients with Child C also demonstrated smaller left caudate nucleus and left amygdala volumes than control patients. Pallidal hyperintensity correlated with smaller striatum volume, which was linearly related to worse cognitive performance. The nonuniform distributed shape abnormalities in the striatum further support the ascending spiral interconnecting theory of the striatum. CONCLUSIONS: These findings strongly suggest lower DGM volume develops according to the severity of the liver cirrhosis. The Mn deposition might contribute the striatum deficit. These findings support the value of additional psychomotor research associated with liver cirrhosis. PMID- 22095961 TI - Correlations between perfusion MR imaging cerebral blood volume, microvessel quantification, and clinical outcome using stereotactic analysis in recurrent high-grade glioma. AB - BACKGROUND AND PURPOSE: Quantifying MVA rather than MVD provides better correlation with survival in HGG. This is attributed to a specific "glomeruloid" vascular pattern, which is better characterized by vessel area than number. Despite its prognostic value, MVA quantification is laborious and clinically impractical. The DSC-MR imaging measure of rCBV offers the advantages of speed and convenience to overcome these limitations; however, clinical use of this technique depends on establishing accurate correlations between rCBV, MVA, and MVD, particularly in the setting of heterogeneous vascular size inherent to human HGG. MATERIALS AND METHODS: We obtained preoperative 3T DSC-MR imaging in patients with HGG before stereotactic surgery. We histologically quantified MVA, MVD, and vascular size heterogeneity from CD34-stained 10-MUm sections of stereotactic biopsies, and we coregistered biopsy locations with localized rCBV measurements. We statistically correlated rCBV, MVA, and MVD under conditions of high and low vascular-size heterogeneity and among tumor grades. We correlated all parameters with OS by using Cox regression. RESULTS: We analyzed 38 biopsies from 24 subjects. rCBV correlated strongly with MVA (r = 0.83, P < .0001) but weakly with MVD (r = 0.32, P = .05), due to microvessel size heterogeneity. Among samples with more homogeneous vessel size, rCBV correlation with MVD improved (r = 0.56, P = .01). OS correlated with both rCBV (P = .02) and MVA (P = .01) but not with MVD (P = .17). CONCLUSIONS: rCBV provides a reliable estimation of tumor MVA as a biomarker of glioma outcome. rCBV poorly estimates MVD in the presence of vessel size heterogeneity inherent to human HGG. PMID- 22095963 TI - Comparison of brain MR images at 1.5T using BLADE and rectilinear techniques for patients who move during data acquisition. AB - BACKGROUND AND PURPOSE: MR imaging of moving patients can be challenging and motion correction techniques have been proposed though some have associated new artifacts. The objective of this study was to semiquantitatively compare brain MR images of moving patients obtained at 1.5T by using partially radial and rectilinear acquisition techniques. MATERIALS AND METHODS: FLAIR, T2-, T1-, and contrast-enhanced T1-weighted image sets of 25 patients (14-94 years) obtained by using BLADE (like PROPELLER, a partially radial acquisition) and rectilinear techniques in the same imaging session were compared by 2 neuroradiologists in terms of extent of the motion artifact, image quality, and lesion visibility. ICC between opinions of the evaluators was calculated. RESULTS: Of the total of 70 image sets, the motion artifact was small in the partially radial images in 43 and in the rectilinear images in 13, and the opinions of the evaluators were discordant in the remaining 14 sets (ICC = 0.63, P < .05). The quality of partially radial images was higher for 36 sets versus 9 rectilinear sets, with disagreement between the 2 evaluators in the remaining 25 (ICC = 0.15, P < .05). Pathologic lesions were better characterized on 37 sets of partially radial images versus 13 sets of rectilinear images, and opinions of the evaluators differed in 20 sets (ICC = 0.90, P < .05). The neuroradiologists deemed 4 sets of rectilinear images nondiagnostic compared with only 1 set of radial images. CONCLUSIONS: The data demonstrate that our application of BLADE sequences reduces the extent of motion artifacts in brain images of moving patients, improving image quality and lesion characterization. PMID- 22095964 TI - The use of in utero MR imaging to delineate developmental brain abnormalities in multifetal pregnancies. AB - BACKGROUND AND PURPOSE: iuMR has been shown to increase the detection rate of developmental abnormalities of the CNS, though most reports are limited to singleton pregnancies. The hypothesis tested in this study was that iuMR performed in multifetal pregnancies will show additional information about fetal CNS abnormalities in a similar proportion of cases when compared with singleton pregnancies. MATERIALS AND METHODS: Fifty women with multifetal pregnancies were recruited consecutively carrying at least 1 fetus with a suspected developmental fetal CNS abnormality on sonography. All had iuMR at the same center by using the same MR imaging protocol. When the sonography and MR imaging reports were discrepant, 1 fetomaternal expert assessed the reports independently to predict in what percentage a change in prognosis/counseling would have occurred if iuMR was included in the diagnostic pathway. RESULTS: There was agreement between the sonography and iuMR reports in 66% and disagreement in 34% of cases. The major cause for discrepancy was the presence or absence of the corpus callosum, which accounted for 10/17 of the disagreements. In 12/17 of the discrepant cases, the effect on management was judged to be significant. CONCLUSIONS: We conclude that iuMR has a similar rate of discrepancy to sonography in multifetal pregnancies compared with the published data concerning singleton pregnancies. Our analysis of the effect on management shows that changes in the decision to consider termination of pregnancy would have occurred in 12/17 of the discrepant cases (ie, in 24% of our cases overall). PMID- 22095965 TI - The new standard for performance of intracranial angioplasty and stent placement after Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) Trial. PMID- 22095966 TI - Physician Quality Reporting System. AB - A brief review of the Physician Quality Reporting System (PQRS) is presented highlighting the program's legislative history, eligibility requirements and incentive payment plan. Specifically, PQRS measures applicable to neuroradiology practice are discussed. Several steps are suggested for individual physicians or group practices to start participation in the program. Resources are also provided for further information on the program requirements and PQRS measures. PMID- 22095967 TI - The predictive value of 3D time-of-flight MR angiography in assessment of brain arteriovenous malformation obliteration after radiosurgery. AB - BACKGROUND AND PURPOSE: The purpose of radiosurgery of bAVMs is complete angiographic obliteration of its nidus. We assessed the diagnostic accuracy of 1.5T T2-weighted MR imaging and TOF-MRA images for detecting nidus obliteration after radiosurgery. MATERIALS AND METHODS: The pre- and postradiosurgery MR images and DSA images from 120 patients who were radiosurgically treated for a bAVM were re-evaluated by 2 observers for patency of the nidus (preradiosurgery) and obliteration (postradiosurgery: final follow-up MR imaging), by using a 3 point scale of confidence. Consensus reading of the DSA after radiosurgery was considered the criterion standard for obliteration. Sensitivity, specificity, PPVs, and NPVs, and overall diagnostic performance by using ROC were determined. RESULTS: Mean bAVM volume during radiosurgery was 3.4 mL (95% CI, 2.6-4.3 mL). Sixty-six patients (55%) had undergone previous endovascular embolization. The mean intervals between radiosurgery and follow-up MR imaging and for DSA, respectively, were 35.6 months (95% CI, 32.3-38.9 months) and 42.1 months (95% CI, 40.3-44.0 months). With ROC, an area under curve of 0.81-0.83 was found. PPVs of final follow-up MR-imaging for definitive obliteration varied between 0.89 [corrected] and 0.95. NPV was 0.52 [corrected] . An average false-positive rate, meaning overestimation of nidus obliteration of 0.10 [corrected] and an average false-negative rate, meaning underestimation of nidus obliteration of 0.42 [corrected] were found. CONCLUSIONS: MRA is insufficient to diagnose obliteration in the follow-up of bAVMs after radiosurgery. A remaining nidus diameter <10 mm seems to be the major limiting factor for reliable assessment of obliteration. We highly recommend follow-up DSA for definitive diagnosis of complete obliteration. PMID- 22095968 TI - Warning: side effects may include a decrease in invasive procedures. PMID- 22095969 TI - Reperfusion by combined thrombolysis and mechanical thrombectomy in acute stroke: effect of collateralization, mismatch, and time to and grade of recanalization on clinical and tissue outcome. AB - BACKGROUND AND PURPOSE: Our research focuses on interventional neuroradiology (stroke treatment including imaging methods) and general neuroimaging with an emphasis on functional MR imaging. Our aim was to determine the efficacy of revascularization (TIMI) of middle cerebral and/or carotid artery occlusion by means of mechanical recanalization techniques and to evaluate the impact of collateralization, mismatch in perfusion CT, time to revascularization, grade of revascularization on tissue, and clinical outcome in patients with acute ischemic stroke. MATERIALS AND METHODS: Thirty-one patients with MCA and/or ICA occlusion were included. Ischemic stroke was diagnosed by NECT, CTA, and volume PCT for grading collateralization and mismatch. Time to recanalization was measured from the onset of stroke to the time point of DSA-proved mechanical recanalization. Tissue outcome was calculated by segmentation of infarct size between pre- and postinterventional CT and percentage mismatch lost. Clinical outcome was determined by the mRS. RESULTS: Twenty-one of 31 patients (61.8%) presented with MCA and 10/31 patients (38.2%), with distal ICA occlusions. Sufficient recanalization (TIMI 2 and 3) was achieved in 23/31 (75%). Clinical evaluation revealed an mRS score of <=2 in 25.5%. Age (r = 0.439, P = .038) and TIMI (r = 0.544, P = .002) showed the strongest correlation with clinical outcome. Time to recanalization, TIMI score, and mismatch were associated with a good tissue outcome in ANOVA. CONCLUSIONS: Favorable outcome after mechanical recanalization of acute MCA and ICA occlusion depends on time to and grade of recanalization, mismatch, and collateralization. These results indicate that multimodal stroke imaging is helpful to guide therapy decisions and to indicate patients amenable for mechanical recanalization. PMID- 22095970 TI - Forniceal involvement in Wernicke encephalopathy. PMID- 22095971 TI - Selective, cytotoxic organoruthenium(II) full-sandwich complexes: a structural, computational and in vitro biological study. AB - A structurally diverse range of lipophilic, cationic eta(6)-arene eta(5) cyclopentadienyl (eta(5)-Cp*) full-sandwich complexes of ruthenium(II) have been prepared and structurally characterized by Fourier-transform IR and NMR spectroscopy, electrospray mass spectrometry, and elemental microanalyses. Computational experiments incorporating the Hartree-Fock theory and the second order Moller-Plesset perturbation theory predict each complex to possess a uniform delta+ electrostatic potential, with the cationic charge of the [RuCp*](+) moiety completely delocalizing throughout the molecular structure of each metallocene. In vitro cytotoxicity studies demonstrate these delocalized lipophilic cations to be potent growth inhibitors of eleven unique tumorigenic cell lines, while exhibiting significantly lower levels of toxicity towards both a normal human fibroblast and a mouse macrophage cell line. Single-crystal X-ray structural determinations are additionally reported for five complexes, [Ru(eta(6)-C(6)H(5)(CH(2))(2)CH(3))(eta(5)-C(5)(CH(3))(5))]BPh(4), [Ru(eta(6) C(6)H(5)CO(2)CH(2)CH(3))(eta(5)-C(5)(CH(3))(5))]BF(4), [Ru(eta(6) C(10)H(8))(eta(5)-(5) (CH(3))(5))]BPh(4), [Ru(eta(6)-C(14)H(10))(eta(5) C(5)(CH(3))(5))]BPh(4), and [Ru(eta(6)-C(16)H(10))(eta(5)-C(5)(CH(3))(5))]BPh(4). PMID- 22095972 TI - Delayed offset detection on figures relative to backgrounds. AB - Recent research suggests that perceptual processing begins earlier for figures than for background regions (B. D. Lester, L. N. Hecht, & S. P. Vecera, 2009). This "prior entry" effect begins to account for reported figural benefits. However, another difference in perceptual processing may also contribute to these observed reports: Figures may also be afforded additional perceptual processing. The current experiments examined this claim and provide evidence that targets presented on figures are perceived as offsetting later than targets appearing on grounds, suggesting extended processing of figures relative to background regions. PMID- 22095973 TI - Increased sensory evidence reverses nonconscious priming during crowding. AB - Sensory adaptation reflects the fact that the responsiveness of a perceptual system changes after the processing of a specific stimulus. Two manifestations of this property have been used in order to infer the mechanisms underlying vision: priming, in which the processing of a target is facilitated by prior exposure to a related adaptor, and habituation, in which this processing is hurt by overexposure to an adaptor. In the present study, we investigated the link between priming and habituation by measuring how sensory evidence (short vs. long adaptor exposure) and perceptual awareness (discriminable vs. undiscriminable adaptor stimulus) affects the adaptive response on a related target. Relying on gaze-contingent crowding, we manipulated independently adaptor discriminability and adaptor duration and inferred sensory adaptation from reaction times on the discrimination of a subsequent oriented target. When adaptor orientation was undiscriminable, we found that increasing its duration reversed priming into habituation. When adaptor orientation was discriminable, priming effects were larger after short exposure, but increasing adaptor duration led to a decrease of priming instead of a reverse into habituation. We discuss our results as reflecting changes in the temporal dynamics of angular orientation processing, depending on the mechanisms associated with perceptual awareness and attentional amplification. PMID- 22095974 TI - Selective attention warps spatial representation: parallel but opposing effects on attended versus inhibited objects. AB - Selective attention not only influences which objects in a display are perceived, but also directly changes the character of how they are perceived--for example, making attended objects appear larger or sharper. In studies of multiple-object tracking and probe detection, we explored the influence of sustained selective attention on where objects are seen to be in relation to each other in dynamic multi-object displays. Surprisingly, we found that sustained attention can warp the representation of space in a way that is object-specific: In immediate recall of the positions of objects that have just disappeared, space between targets is compressed, whereas space between distractors is expanded. These effects suggest that sustained attention can warp spatial representation in unexpected ways. PMID- 22095975 TI - If they were to vote, they would vote for us. AB - In two field studies, we examined whether voters overestimate support for their political party among nonvoters. In Study 1, voters estimated the percentage of votes their party would receive in an upcoming election, and this percentage increased when voters estimated the percentage of votes their party would receive if nonvoters also were to vote. In Study 2, participants overestimated support for their party even when we made them explicitly aware of current levels of this support by presenting them with poll-based forecasts of election results. Furthermore, Study 2 demonstrated that commitment to vote for a specific party predicted the degree of overestimation. Our results imply that highly committed voters are particularly likely to project support for their party onto nonvoters. Implications for the literature on social projection and social identity are discussed. PMID- 22095976 TI - What do infants remember when they forget? Location and identity in 6-month-olds' memory for objects. AB - What does an infant remember about a forgotten object? Although at age 6 months, infants can keep track of up to three hidden objects, they can remember the featural identity of only one. When infants forget the identity of an object, do they forget the object entirely, or do they retain an inkling of it? In a looking time study, we familiarized 6-month-olds with a disk and a triangle placed on opposite sides of a stage. During test trials, we hid the objects one at a time behind different screens, and after hiding the second object, we removed the screen where the first object had been hidden. Infants then saw the expected object, the unexpected other object, or the empty stage. Bayes factor analysis showed that although the infants did not notice when the object changed shape, they were surprised when it vanished. This finding indicates that infants can represent an object without its features. PMID- 22095977 TI - G protein-coupled receptor kinase-5 attenuates atherosclerosis by regulating receptor tyrosine kinases and 7-transmembrane receptors. AB - OBJECTIVE: G protein-coupled receptor kinase-5 (GRK5) is a widely expressed Ser/Thr kinase that regulates several atherogenic receptors and may activate or inhibit nuclear factor-kappaB (NF-kappaB). This study sought to determine whether and by what mechanisms GRK5 affects atherosclerosis. METHODS AND RESULTS: Grk5(-/ )/Apoe(-/-) mice developed 50% greater aortic atherosclerosis than Apoe(-/-) mice and demonstrated greater proliferation of macrophages and smooth muscle cells (SMCs) in atherosclerotic lesions. In Apoe(-/-) mice, carotid interposition grafts from Grk5(-/-) mice demonstrated greater upregulation of cell adhesion molecules than grafts from wild-type mice and, subsequently, more atherosclerosis. By comparing Grk5(-/-) with wild-type cells, we found that GRK5 desensitized 2 key atherogenic receptor tyrosine kinases: the platelet-derived growth factor receptor-beta in SMCs, by augmenting ubiquitination/degradation; and the colony-stimulating factor-1 receptor (CSF-1R) in macrophages, by reducing CSF-1-induced tyrosyl phosphorylation. GRK5 activity in monocytes also reduced migration promoted by the 7-transmembrane receptor for monocyte chemoattractant protein-1 CC chemokine receptor-2. Whereas GRK5 diminished NF-kappaB-dependent gene expression in SMCs and endothelial cells, it had no effect on NF-kappaB activity in macrophages. CONCLUSIONS: GRK5 attenuates atherosclerosis through multiple cell type-specific mechanisms, including reduction of SMC and endothelial cell NF-kappaB activity and desensitization of receptor-specific signaling through the monocyte CC chemokine receptor-2, macrophage CSF-1R, and the SMC platelet-derived growth factor receptor-beta. PMID- 22095978 TI - Arteriolar function in visceral adipose tissue is impaired in human obesity. AB - OBJECTIVE: The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. METHODS AND RESULTS: In 30 obese subjects (age 42+/-11 years, body mass index 46+/-11 kg/m(2)) undergoing bariatric surgery, we intraoperatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75-250 MUm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Nonendothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase inhibition with N(omega)-nitro-l-arginine methyl ester reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and had a higher capacity for cytokine production ex vivo. CONCLUSIONS: Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity. PMID- 22095979 TI - Calpains contribute to vascular repair in rapidly progressive form of glomerulonephritis: potential role of their externalization. AB - OBJECTIVE: Calpains, calcium-activated proteases, mediate the angiogenic signals of vascular endothelial growth factor. However, their involvement in vascular repair has not been investigated and the underlying mechanisms remain to be fully elucidated. METHODS AND RESULTS: A rapidly progressive form of glomerulonephritis in wild type and transgenic mice expressing high levels of calpastatin, a calpain specific inhibitor, was studied. Calpastatin transgene expression prevented the repair of peritubular capillaries and the recovery of renal function, limiting mouse survival. In vitro analysis detected a significant reduction of both intracellular and extracellular calpain activities in transgene expressing cells, whereas Western blotting revealed that proangiogenic factors vascular endothelial growth factor and norepinephrine increased calpain exteriorization. In vitro, extracellular calpains increased endothelial cell proliferation, migration and capillary tube formation. In vivo, delivery of nonpermeable extracellular calpastatin was sufficient to blunt angiogenesis and vascular repair. Endothelial cell response to extracellular calpains was associated with fibronectin cleavage, generating fibronectin fragments with proangiogenic capacity. In vivo, fibronectin cleavage was limited in the kidney of calpastatin transgenic mice with nephritis. CONCLUSIONS: This study demonstrates that externalized calpains participate in angiogenesis and vascular repair, partly by promoting fibronectin cleavage and thereby amplifying vascular endothelial growth factor efficiency. Thus, manipulation of calpain externalization may have therapeutic implications to control angiogenesis. PMID- 22095980 TI - S100A8 and S100A9 in cardiovascular biology and disease. AB - There is recent and widespread interest in the damage-associated molecular pattern molecules S100A8 and S100A9 in cardiovascular science. These proteins have a number of interesting features and functions. For example, S100A8 and S100A9 (S100A8/A9) have both intracellular and extracellular actions, they are abundantly expressed in inflammatory and autoimmune states, primarily by myeloid cells but also by other vascular cells, and they modulate inflammatory processes, in part through Toll-like receptor 4 and the receptor for advanced glycation end products. S100A8/A9 also have anti-inflammatory and immune regulatory actions. Furthermore, increased plasma levels of S100A8/A9 predict cardiovascular events in humans, and deletion of these proteins partly protects Apoe(-)(/)(-) mice from atherosclerosis. Understanding the roles of S100A8 and S100A9 in vascular cell types and the mechanisms whereby these proteins mediate their biological effects may offer new therapeutic strategies to prevent, treat, and predict cardiovascular diseases. PMID- 22095981 TI - Inhibition of microRNA-29 enhances elastin levels in cells haploinsufficient for elastin and in bioengineered vessels--brief report. AB - OBJECTIVE: The goal of this study was to determine whether antagonizing microRNA (miR)-29 enhances elastin (ELN) levels in cells and tissues lacking ELN. METHODS AND RESULTS: miR-29 mimics reduced ELN levels in fibroblasts and smooth muscle cells, whereas miR-29 inhibition increased ELN levels. Antagonism of miR-29 also increased ELN levels in cells from patients haploinsufficient for ELN and in bioengineered human vessels. CONCLUSION: miR-29 antagonism may promote increased ELN levels during conditions of ELN deficiencies. PMID- 22095982 TI - Pharmacological suppression of hepcidin increases macrophage cholesterol efflux and reduces foam cell formation and atherosclerosis. AB - OBJECTIVE: We recently reported that lowering of macrophage free intracellular iron increases expression of cholesterol efflux transporters ABCA1 and ABCG1 by reducing generation of reactive oxygen species. In this study, we explored whether reducing macrophage intracellular iron levels via pharmacological suppression of hepcidin can increase macrophage-specific expression of cholesterol efflux transporters and reduce atherosclerosis. METHODS AND RESULTS: To suppress hepcidin, increase expression of the iron exporter ferroportin, and reduce macrophage intracellular iron, we used a small molecule inhibitor of bone morphogenetic protein (BMP) signaling, LDN 193189 (LDN). LDN (10 mg/kg IP b.i.d.) was administered to mice, and its effects on atherosclerosis, intracellular iron, oxidative stress, lipid efflux, and foam cell formation were measured in plaques and peritoneal macrophages. Long-term LDN administration to apolipoprotein E-/- mice increased ABCA1 immunoreactivity within intraplaque macrophages by 3.7-fold (n=8; P=0.03), reduced Oil Red O-positive lipid area by 50% (n=8; P=0.02), and decreased total plaque area by 43% (n=8; P=0.001). LDN suppressed liver hepcidin transcription and increased macrophage ferroportin, lowering intracellular iron and hydrogen peroxide production. LDN treatment increased macrophage ABCA1 and ABCG1 expression, significantly raised cholesterol efflux to ApoA-1, and decreased foam cell formation. All preceding LDN-induced effects on cholesterol efflux were reversed by exogenous hepcidin administration, suggesting modulation of intracellular iron levels within macrophages as the mechanism by which LDN triggers these effects. CONCLUSIONS: These data suggest that pharmacological manipulation of iron homeostasis may be a promising target to increase macrophage reverse cholesterol transport and limit atherosclerosis. PMID- 22095983 TI - Xanthine oxidoreductase is involved in macrophage foam cell formation and atherosclerosis development. AB - OBJECTIVE: Hyperuricemia is common in patients with metabolic syndrome. We investigated the role of xanthine oxidoreductase (XOR) in atherosclerosis development, and the effects of the XOR inhibitor allopurinol on this process. METHODS AND RESULTS: Oral administration of allopurinol to ApoE knockout mice markedly ameliorated lipid accumulation and calcification in the aorta and aortic root. In addition, allopurinol treatment or siRNA-mediated gene knockdown of XOR suppressed transformation of J774.1 murine macrophage cells, treated with acetylated LDL or very low density lipoprotein (VLDL) into foam cells. This inhibitory effect of allopurinol was also observed in primary cultured human macrophages. In contrast, overexpression of XOR promoted transformation of J774.1 cells into foam cells. Interestingly, SR-A1, SR-B1, SR-B II, and VLDL receptors in J774.1 cells were reduced by XOR knockdown, and increased by XOR overexpression. Conversely, expressions of ABCA1 and ABCG1 were increased by XOR knockdown and suppressed by XOR overexpression. Finally, productions of inflammatory cytokines accompanied by foam cell formation were also reduced by allopurinol administration. CONCLUSIONS: These results strongly suggest XOR activity and/or its expression level to contribute to macrophage foam cell formation. Thus, XOR inhibitors may be useful for preventing atherosclerosis. PMID- 22095984 TI - Association of testosterone levels with endothelial function in men: results from a population-based study. AB - OBJECTIVE: Because population-based data are lacking, we assessed the cross sectional association between serum testosterone levels and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in men from the population-based Study of Health in Pomerania. METHODS AND RESULTS: Personal characteristics, including major cardiovascular confounders, were collected in 722 men, aged 25 to 85 years. Serum total testosterone and sexual hormone-binding globulin (SHBG) levels were determined by chemiluminescence immunoassays. Free testosterone levels were calculated according to the law of mass action. FMD and NMD measurements were performed using standardized ultrasound techniques. FMD and NMD values below the 20th percentile were considered decreased. Multivariable logistic regression analyses revealed an association for each decrement of total testosterone standard deviation (6.0 nmol/L) with decreased FMD after adjustment for potential confounders (odds ratio 1.30, 95% confidence interval 1.04-1.63; P=0.023). Multiple adjusted findings for free testosterone were similar (odds ratio 1.37, 95% confidence interval 1.06-1.76; P=0.016). There was no such association of SHBG levels with decreased FMD. Neither testosterone nor SHBG levels were significantly associated with decreased NMD. CONCLUSIONS: Lower serum total and free testosterone levels are associated with impaired endothelial function in this population-based sample of men. PMID- 22095985 TI - Regulation of peroxisome proliferator-activated receptor-gamma by angiotensin II via transforming growth factor-beta1-activated p38 mitogen-activated protein kinase in aortic smooth muscle cells. AB - OBJECTIVE: Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands attenuate angiotensin II (Ang II)-induced atherosclerosis through interactions with vascular smooth muscle cell (VSMC)-specific PPARgamma in hypercholesterolemic mice. Therefore, the purpose of this study was to determine the mechanism of Ang II-mediated intracellular regulation of PPARgamma in VSMCs. METHODS AND RESULTS: Incubation of cultured mouse aortic VSMCs with Ang II for 24 hours reduced abundance of PPARgamma protein, mRNA, and transcriptional activity (P<0.001). This effect was attenuated by an angiotensin type 1 receptor antagonist, losartan. Ang II-induced PPARgamma reduction was dependent on stimulation of transforming growth factor (TGF)-beta1 as demonstrated using either a neutralizing antibody or small interfering RNA (siRNA). Ang II-induced TGF-beta1 secretion was dependent on epidermal growth factor receptor kinase activation through reactive oxygen species production. Inhibition of p38 mitogen activated protein kinase by SB203580 or siRNA inhibited both Ang II- and TGF beta1-induced PPARgamma reduction. Blockade of TGF-beta1 decreased p38 phosphorylation induced by Ang II. siRNA-mediated inhibition of histone deacetylase 3 attenuated p38-mediated reductions in PPARgamma abundance. CONCLUSIONS: These findings suggest that Ang II decreases PPARgamma abundance in cultured VSMCs via an angiotensin type 1 receptor-dependent secretion of TGF beta1 via phosphorylation of p38 mitogen-activated protein kinase and histone deacetylase 3. PMID- 22095986 TI - NADPH oxidase 4 mediates monocyte priming and accelerated chemotaxis induced by metabolic stress. AB - OBJECTIVE: Metabolic disorders increase monocyte chemoattractant protein-1 (MCP 1)-induced monocyte chemotaxis in mice. The goal of this study was to determine the molecular mechanisms responsible for the enhanced responsiveness of monocytes to chemoattractants induced by metabolic stress. METHODS AND RESULTS: Chronic exposure of monocytes to diabetic conditions induced by human LDL plus high D glucose concentrations (LDL+HG) promoted NADPH Oxidase 4 (Nox4) expression, increased intracellular H(2)O(2) formation, stimulated protein S glutathionylation, and increased chemotaxis in response to MCP-1, platelet derived growth factor B, and RANTES. Both H(2)O(2) added exogenously and overexpression of Nox4 mimicked LDL+HG-induced monocyte priming, whereas Nox4 knockdown protected monocytes against metabolic stress-induced priming and accelerated chemotaxis. Exposure of monocytes to LDL+HG promoted the S glutathionylation of actin, decreased the F-actin/G-actin ratio, and increased actin remodeling in response to MCP-1. Preventing LDL+HG-induced protein S glutathionylation by overexpressing glutaredoxin 1 prevented monocyte priming and normalized monocyte chemotaxis in response to MCP-1. Induction of hypercholesterolemia and hyperglycemia in C57BL/6 mice promoted Nox4 expression and protein S-glutathionylation in macrophages, and increased macrophage recruitment into MCP-1-loaded Matrigel plugs implanted subcutaneous in these mice. CONCLUSIONS: By increasing actin-S-glutathionylation and remodeling, metabolic stress primes monocytes for chemoattractant-induced transmigration and recruitment to sites of vascular injury. This Nox4-dependent process provides a novel mechanism through which metabolic disorders promote atherogenesis. PMID- 22095988 TI - Transforming growth factor-beta-induced endothelial-to-mesenchymal transition is partly mediated by microRNA-21. AB - OBJECTIVE: MicroRNAs are a class of small ribonucleotides regulating gene/protein targets by transcript degradation or translational inhibition. Transforming growth factor-beta (TGF-beta) is involved in cardiac fibrosis partly by stimulation of endothelial-to-mesenchymal transition (EndMT). Here, we investigated whether microRNA (miR)-21, a microRNA enriched in fibroblasts and involved in general fibrosis, has a role in cardiac EndMT. METHODS AND RESULTS: TGF-beta treatment of endothelial cells significantly increased miR-21 expression and induced EndMT characterized by suppression of endothelial and increase of fibroblast markers. Overexpression of miR-21 alone also stimulated EndMT. Importantly, miR-21 blockade by transfection of specific microRNA inhibitors partly prevented TGF-beta-induced EndMT. Mechanistically, miR-21 silenced phosphatase and tensin homolog in endothelial cells, resulting in activation of the Akt-pathway. Akt inhibition partly restored TGF-beta-mediated loss of endothelial markers during EndMT. In vivo, pressure overload of the left ventricle led to increased expression of miR-21 in sorted cardiac endothelial cells, which displayed molecular and phenotypic signs of EndMT. This was attenuated by treatment of mice subjected to left ventricular pressure overload with an antagomir against miR-21. CONCLUSIONS: TGF-beta-mediated EndMT is regulated at least in part by miR-21 via the phosphatase and tensin homolog/Akt pathway. In vivo, antifibrotic effects of miR-21 antagonism are partly mediated by blocking EndMT under stress conditions. PMID- 22095987 TI - Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations. AB - OBJECTIVE: We investigated the impact of lipoprotein lipase (LPL) gene mutations on apolipoprotein B (apoB)-100 metabolism. METHODS AND RESULTS: We studied 3 subjects with familial LPL deficiency; 14 subjects heterozygous for the LPL gene mutations Gly188Glu, Trp64Stop, and Ile194Thr; and 10 control subjects. Very-low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low density lipoprotein (LDL)-apoB-100 kinetics were determined in the fed state using stable isotope methods and compartmental modeling. Compared with controls, familial LPL deficiency had markedly elevated plasma triglycerides and lower VLDL apoB-100 fractional catabolic rate (FCR), IDL-apoB-100 FCR, VLDL-to-IDL conversion, and VLDL-apoB-100 production rate (P<0.01). Compared with controls, Gly188Glu had higher plasma triglyceride and VLDL- and IDL-apoB-100 concentrations and lower VLDL- and IDL-apoB-100 FCR (P<0.05). Plasma triglycerides were not different, but IDL-apoB-100 concentration and production rate and VLDL-to-IDL conversion were lower in Trp64Stop compared with controls (P<0.05). No differences between controls and Ile194Thr were observed. CONCLUSIONS: Our results confirm that hypertriglyceridemia is a key feature of familial LPL deficiency. This is due to impaired VLDL- and IDL-apoB-100 catabolism and VLDL-to-IDL conversion. Single-allele mutations of the LPL gene result in modest to elevated plasma triglycerides. The changes in plasma triglycerides and apoB-100 kinetics are attributable to the effects of the LPL genotype. PMID- 22095989 TI - Science to practice: Which approaches to combination interventional oncologic therapy hold the greatest promise of obtaining maximal clinical benefit? AB - Soundararajan et al (1) were able to demonstrate that combination therapy of radiofrequency (RF) ablation with rhenium 186 (186Re)--labeled liposomal doxorubicin resulted in better drug uptake and reduced tumor growth compared with other therapies tested in a rodent head and neck tumor model. In essence, this "triple" combination therapy of chemotherapy, radiation, and thermal ablation induced significantly smaller viable tumor volume compared with the therapies tested alone at histopathologic examination. PMID- 22095990 TI - Uncertainties in the diagnosis of lumbar spinal stenosis. PMID- 22095991 TI - Functional coronary imaging with magnetic resonance: a "renaissance"? PMID- 22095992 TI - Lung cancer and chronic obstructive pulmonary disease: the story goes on. PMID- 22095993 TI - A framework for assessing the value of diagnostic imaging in the era of comparative effectiveness research. AB - In June 2009, the Federal Coordinating Council for Comparative Effectiveness Research submitted a report to the President and Congress in which the Council described the purpose of comparative effectiveness research (CER) as developing evidence-based information for interventions and determining under what circumstances an intervention is effective (1). With the enactment of the Patient Protection and Affordable Care Act, a Patient-centered Outcomes Research Institute (PCORI) was established to assist decision makers in making evidence based health decisions through synthesis and dissemination of clinical CER of health interventions (2). Its founding has underscored a heightened need for health policy makers to consider the impact of health care technologies on final outcomes of interest--for example, functional status, quality of life, disability, major clinical events, and mortality (3-5). PMID- 22095994 TI - Whole-body diffusion-weighted MR imaging in cancer: current status and research directions. AB - Diffusion-weighted (DW) magnetic resonance (MR) imaging is emerging as a powerful clinical tool for directing the care of patients with cancer. Whole-body DW imaging is almost at the stage where it can enter widespread clinical investigations, because the technology is stable and protocols can be implemented for the majority of modern MR imaging systems. There is a continued need for further improvements in data acquisition and analysis and in display technologies. Priority areas for clinical research include clarification of histologic relationships between tissues of interest and DW MR imaging biomarkers at diagnosis and during therapy response. Because whole-body DW imaging excels at bone marrow assessments at diagnosis and for therapy response, it can potentially address a number of unmet clinical and pharmaceutical requirements. There are compelling needs to document and understand how common and novel treatments affect whole-body DW imaging results and to establish response criteria that can be tested in prospective clinical studies that incorporate measures of patient benefit. PMID- 22095995 TI - Computer-aided diagnosis: how to move from the laboratory to the clinic. AB - Computer-aided diagnosis (CAD), encompassing computer-aided detection and quantification, is an established and rapidly growing field of research. In daily practice, however, most radiologists do not yet use CAD routinely. This article discusses how to move CAD from the laboratory to the clinic. The authors review the principles of CAD for lesion detection and for quantification and illustrate the state-of-the-art with various examples. The requirements that radiologists have for CAD are discussed: sufficient performance, no increase in reading time, seamless workflow integration, regulatory approval, and cost efficiency. Performance is still the major bottleneck for many CAD systems. Novel ways of using CAD, extending the traditional paradigm of displaying markers for a second look, may be the key to using the technology effectively. The most promising strategy to improve CAD is the creation of publicly available databases for training and validation. This can identify the most fruitful new research directions, and provide a platform to combine multiple approaches for a single task to create superior algorithms. PMID- 22095996 TI - Renal perfusion 3-T MR imaging: a comparative study of arterial spin labeling and dynamic contrast-enhanced techniques. AB - PURPOSE: To investigate the feasibility of and correlation between arterial spin labeling (ASL) and dynamic contrast material-enhanced (DCE) 3-T magnetic resonance (MR) imaging in the measurement of renal blood flow (RBF). MATERIALS AND METHODS: The review board approved this study. Nineteen healthy volunteers (seven women, 12 men; age range, 25-68 years) were recruited, and each provided written informed consent. MR imaging was performed with a 3-T whole-body system. Each subject underwent back-to-back ASL and DCE MR imaging. Ten runs of ASL imaging were performed by using the pseudocontinuous tagging scheme, and each run required an 18-second breath hold. For DCE imaging, a gadopentetate dimeglumine bolus (0.0125 mmol per kilogram of body weight) was administrated intravenously in all subjects except two; in the latter subjects, a 0.025 mmol/kg gadopentetate dimeglumine bolus was administered to evaluate the T1 saturation effect. RBF was quantified with both techniques and in both the cortex and the medulla. Agreement was evaluated for RBF measurements obtained with ASL imaging and those obtained with DCE imaging by using correlation analysis. RESULTS: RBF was apparently overestimated with 0.025 mmol/kg gadopentetate dimeglumine, which is a concentration that is commonly adopted for 1.5-T DCE. RBF was 227 mL/100 mL/min +/- 30 (standard deviation) in the cortex and 101 mL/100 mL/min +/- 21 in the medulla, as measured with ASL imaging, and 272 mL/100 mL/min +/- 60 in the cortex and 122 mL/100 mL/min +/- 30 in the medulla, as measured with DCE imaging. In the cortex, measurements obtained with ASL and DCE imaging exhibited a linear correlation (r = 0.66; statistical power, 0.8 at the 5% significance level) and fair agreement (intraclass correlation coefficient, 0.41). CONCLUSION: ASL and DCE 3-T MR imaging are feasible in the quantification of cortical renal perfusion, yielding measurements that are correlated but not entirely comparable. Intermodality differences have yet to be solved. PMID- 22095998 TI - Case 176: Neuro-sweet syndrome. PMID- 22095999 TI - Accurate definition of superficial and deep fascia. PMID- 22096000 TI - A few considerations on "sonoelastography of the plantar fascia". PMID- 22096001 TI - Honorary authorship: a hawk hovers over the lower-rank academic. PMID- 22096002 TI - Biliary atresia in neonates and infants. PMID- 22096003 TI - CTDIvol, DLP, and effective dose are excellent measures for use in CT quality improvement. PMID- 22096004 TI - Satisfaction of search in radiographic modalities. PMID- 22096005 TI - Transient hepatic echogenicity differences at contrast-enhanced US. PMID- 22096008 TI - The frequency of metabolic syndrome is higher among PCOS Brazilian women with menstrual irregularity plus hyperandrogenism. AB - Polycystic ovary syndrome (PCOS) has a heterogeneous phenotypic distribution that can potentially lead to variations in metabolic repercussions. A cross-sectional study was conducted with 372 women of reproductive age (146 of whom were ovulatory and 226 with PCOS) divided into groups according to PCOS phenotype: (i) complete phenotype involving menstrual irregularity (MI), hyperandrogenism (H), and ultrasound (US) findings of polycystic ovaries (132 patients); (ii) MI + H (18 patients); (iii) MI + US (51 patients); and (iv) H + US (25 patients). The frequencies of metabolic syndrome (MetS) were 45.4%, 38.9%, 33.3%, 36%, and 8.2% for the MI + H + US, MI + H, MI + US, H + US, and control groups (P < .01), respectively. In logistic regression, body mass index ([BMI] odds ratio [OR]: 1.1, 95% confidence interval [CI] 1.1-1.2) and the association of the complete phenotype with MI + H (OR: 5.8 CI95% [2.2-15.8) were independent predictors of the occurrence of MetS. The defining characteristics of MetS were more frequently found in women with PCOS than in controls, regardless of the phenotype (P < .01 for each variable). In conclusion, the frequency of MetS is similar for various PCOS phenotypes among young Brazilian women from the Southeast region of the country, although only BMI and the presence of MI + H, regardless of the presence of US findings, were more predictive of the development of MetS. PMID- 22096007 TI - Adipocytes enhance the proliferation of human leiomyoma cells via TNF-alpha proinflammatory cytokine. AB - OBJECTIVE: Obesity is a well-documented risk factor for uterine leiomyoma with a major impact on women health and health care system of the nation. Obesity is associated with increased secretion of adipokines that significantly influence growth and proliferation of tumor stroma and malignant cells. Adipokines, such as tumor necrosis factor alpha (TNF-alpha), are produced in the adipose tissue with concomitant expression in other organs and tissues. Increased and sustained cytokine production is associated with alterations in cell growth and differentiation. We, therefore, explored the influence of human adipocytes (SW872 cells)-mediated biological humoral factors on human uterine leiomyoma (HuLM) cells. METHODS: We measured cell proliferation and expression of cell proliferating proteins (proliferating cell nuclear antigen [PCNA], cyclin D1, and B-cell lymphoma 2 [BCL-2]) in human leiomyoma cells cocultured with SW872 cells. SW872-conditioned media was neutralized for TNF-alpha and proliferation of HuLM cells was observed along with antiapoptotic marker, BCL-2, using Western immunoblot. RESULTS: We found that both SW872-conditioned media and coculture with SW872 cells increased HuLM cell proliferation significantly (P < .05). We determined that this effect was associated with the upregulation of specific markers for proliferation, such as PCNA, cyclin D1, and BCL-2 (P < .05). Furthermore, the addition of neutralizing antibodies, anti-TNF-alpha, to SW872 conditioned media reversed the proliferation of leiomyoma cells and induced apoptosis as indicated by the reduced expression of antiapoptotic marker BCL-2. CONCLUSIONS: SW872 cells secrete TNF-alpha, which is associated with a proliferative gene profile in HuLM cells and may play a role in initiation and/or progression of uterine leiomyoma. PMID- 22096009 TI - A combination of illness invalidation from the work environment and helplessness is associated with embitterment in patients with FM. AB - OBJECTIVES: The aim of this study in employed people with FM was to test the hypothesis that embitterment is a function of the joint experience of invalidation from the work environment and helplessness regarding one's illness. METHODS: Sixty-four full-time (36%) or part-time (64%) employed patients with FM (60 females, mean age 45 years) completed the Illness Invalidation Inventory (3*I) to assess work-related discounting and lack of understanding, the Illness Cognition Questionnaire (ICQ) to assess helplessness and the Bern Embitterment Inventory (BEI) to assess embitterment. Hierarchical regression analysis was performed. RESULTS: Sixteen percent of the participants experienced embitterment levels in the clinical range. The interaction or combination of discounting and helplessness (P = 0.02) and the combination of lack of understanding and helplessness (P = 0.04) were associated with greater embitterment. CONCLUSIONS: The construct of embitterment has substantial face validity and may result from a combination of invalidation and helplessness. Whereas helplessness is a common target of cognitive-behavioural therapy, evidence-based interventions to redress invalidation and embitterment are needed. It is possible, however, to target invalidation by educating people in the work environment about the consequences of FM and patients' valid needs for work that is manageable, given each patient's specific health-related limitations. PMID- 22096010 TI - Necrotizing fasciitis in a rheumatoid arthritis patient treated with tocilizumab. PMID- 22096011 TI - Sustained clinical remission in rheumatoid arthritis: prevalence and prognostic factors in an inception cohort of patients treated with conventional DMARDS. AB - OBJECTIVE: Clinical remission is now a realistic goal in managing RA following the introduction of biologic agents. As there are limited data on sustained remission in conventionally treated RA, this study examines prevalence and predictive factors of sustained remission in a pre-biologic inception cohort of RA. METHODS: Patients with recent onset RA and before use of DMARDs were recruited from nine centres. Standard clinical and radiological assessments were recorded at baseline and yearly. Point remission was defined by DAS of <1.6, and sustained remission if DAS was <1.6 at all 3-, 4- and 5-year follow-ups. Sustained remission was compared with baseline features, with mortality and with radiological and functional progression in 704 patients. RESULTS: Point remission at 3, 4 and 5 years was 25, 26 and 22%, respectively. Eleven per cent (n = 78) had sustained remission. Male sex, short duration of symptoms and less tender joints at baseline were independent predictors of sustained remission. These patients had fewer DMARD therapies and less radiographic progression by 5 years. Mean HAQ decreased from 0.79 to 0.13 (P < 0.001) in sustained remission, compared with an increase from 0.92 to 1.1 (P < 0.001) in the non-remission group. CONCLUSION: Sustained clinical remission by 5 years with conventional DMARDs was 11%, half as likely as point remission. Prognostic factors were similar to comparable studies and simple to measure. Patients in sustained clinical remission showed less structural damage and better functional outcomes. PMID- 22096012 TI - Factors associated with foot pain severity and foot-related disability in individuals with first metatarsophalangeal joint OA. AB - OBJECTIVE: To determine whether participant characteristics and localized structural factors are associated with foot pain and foot-related disability in patients with symptomatic first MTP joint OA. METHODS: One hundred and fifty-one participants (56 women and 95 men) aged 22-81 [mean age 54.5 (11.2)] years with symptomatic first MTP joint OA underwent a standardized clinical interview and assessment. Participant characteristics [age, gender, height, weight, BMI, duration of symptoms and total years of formal education (education attainment)] and localized factors (first MTP joint dorsiflexion range of motion, severity of radiographic OA, foot posture and plantarflexion strength of the hallux) were determined as potentially associated variables. Outcome variables were foot pain and foot-related disability, determined using the Foot Health Status Questionnaire. Univariate analyses were performed between potentially associated variables and outcome variables. Variables with significant univariate associations were then entered into multivariate linear regression models to identify independently associated variables. RESULTS: Education attainment and BMI were both significantly and independently associated with foot pain severity and foot-related disability. However, these variables only explained ~10-12% of the variance in foot pain and foot-related disability. CONCLUSIONS: People with symptomatic first MTP joint OA that have an increased BMI and/or lower level of education attainment experience more foot pain and have greater foot-related disability. Prospective studies are required to confirm these findings and identify other factors associated with foot pain and foot-related disability in people with symptomatic first MTP joint OA. PMID- 22096013 TI - Childhood-onset disease carries a higher risk of low bone mineral density in an adult population of systemic lupus erythematosus. AB - OBJECTIVE: To study the BMD of patients with SLE according to the age of disease onset. METHODS: Consecutive SLE patients were screened for BMD at the hip, lumbar spine and whole body by the dual-energy X-ray absorptiometry (DXA). Comparison was made between patients who had disease onset in childhood (<18 years) and adulthood (>=18 years). Factors associated with low BMD were studied by linear regression. RESULTS: A total of 395 SLE patients were studied (94% women; 11% childhood-onset disease). Osteoporosis of the lumbar spine and the hip/femoral neck was present in 20 and 10% of the patients, respectively. Childhood-onset SLE patients were less likely to be post-menopausal, but had significantly lower BMI, longer SLE duration and a higher frequency of ever use of high-dose CSs, CYC and AZA. Despite a significantly younger age, the BMD of the hip, femoral neck and lumbar spine was significantly lower in childhood- than adult-onset SLE patients. In linear regression models, childhood-onset disease was an independent factor for lower BMD at the lumbar spine (beta = -0.18; P = 0.002), hip (beta = -0.20; P = 0.001) and femoral neck (beta = -0.16; P = 0.01) after adjustment for age, sex, BMI, smoking, menopause, SLE duration and damage index, duration and current dose of prednisolone treatment and the ever use of high-dose glucocorticoids, other immunosuppressive agents, calcium, vitamin D and the bisphosphonates. CONCLUSIONS: In adult SLE patients, childhood-onset disease carries a higher risk of osteoporosis, which may possibly be related to a higher cumulative dose of glucocorticoids used for more active disease and failure to achieve a normal peak bone mass during puberty. PMID- 22096014 TI - The incidence of permanent work disability in patients with rheumatoid arthritis in Sweden 1990-2010: before and after introduction of biologic agents. AB - OBJECTIVE: To explore the incidence of disability pension (DP) due to RA as an estimation of permanent work disability before and after introduction of biologic drugs. METHODS: The annual incidence of DP was derived from the Swedish National Social Insurance Register and rates of DP due to RA were compared with the total amount of new DPs. RESULTS: The incidence of DP due to RA has decreased over recent years, coinciding with earlier and more aggressive treatment with DMARDs and biologics. A similar declining incidence of DP was simultaneously seen in patients with all diagnoses in the general population. The decrease in DPs was, however, larger for RA and was evident even before introduction of biologics. In 1990, the proportion of DPs caused by RA was 1.9% out of total amount of DPs, decreasing to 1.5% in 2000 and to 1% in 2009. This may reflect effects of treatment, but may also be due to changing political policies as well as changes in age structure, increasing educational level and less physically demanding jobs. CONCLUSION: The decrease in DPs due to RA coincides with new treatment strategies as well as with decreasing levels of DPs in patients with all diagnoses. Prevailing political and economic conditions have a large impact on permanent work disability and may affect patients with various diagnoses in different ways. To determine if the decline is a true effect of better treatment, there is a need for further investigations, taking possible confounding factors into account. PMID- 22096015 TI - Early treatment with rituximab in newly diagnosed systemic lupus erythematosus patients: a steroid-sparing regimen. AB - OBJECTIVES: To assess the effectiveness of B-cell depletion therapy (BCDT) as a steroid-sparing treatment in newly diagnosed SLE patients. METHODS: Eight female SLE patients were treated with BCDT using a rituximab/CYC-based regimen aiming to avoid the routine use of oral steroids. Post-treatment, patients were given AZA. The BILAG disease activity index was used for clinical assessment. Serum anti dsDNA, complement (C3), ESR, circulating B lymphocytes (CD19(+)) and protein : creatinine ratio were tested at 0, 1, 3, 6 and 12 months post-treatment. Disease activity and steroid requirement over the first 6 months of treatment were compared with three SLE patients treated conventionally, each carefully matched for ethnicity, sex, age at disease onset and disease duration at diagnosis. RESULTS: All patients achieved B-cell depletion (CD19 count <0.005 * 10(9)/l). The mean decrease in global BILAG at 6 months for the BCDT patients was -12.0 vs 13.22 for the controls. Post-BCDT, no patient developed any significant deterioration, mean ESR fell from 70.12 to 17.14 mm/h at 6 months, mean serum anti-dsDNA antibody levels fell by >70% at 1 month and serum C3 level normalized in two patients by 6 months. There were no adverse events. The mean cumulative prednisolone dose at 6 months for the BCDT patients was 1287.3 mg (range 250 4501.8 mg) vs 2834.6 mg (range 0-6802.5 mg) for the controls. CONCLUSION: Early treatment of SLE patients with BCDT is safe and effective and enables a reduction in the overall steroid burden. PMID- 22096016 TI - Turning points for perpetrators of intimate partner violence. AB - Understanding why and how perpetrators of intimate partner violence (IPV) change their behavior is an important goal for both policy development and clinical practice. In this study, the authors investigated the concept of "turning points" for perpetrators of IPV by conducting a systematic review of qualitative studies that investigated the factors, situations, and attitudes that facilitated perpetrators' decisions to change their abusive behavior. Two literature databases were searched and six studies were found that met the inclusion criteria for the systematic review. Most included participants from batterer intervention programs (BIPs). The data indicate that community, group, and individual processes all contribute to perpetrators' turning points and behavioral change. These include identifying key incidents that precede change, taking responsibility for past behavior, learning new skills, and developing relationships within and outside of the BIP. By using a qualitative systematic review, the authors were able to generate a more complete understanding of the catalysts for and process of change in these individuals. Further research, combining quantitative and qualitative approaches, will be helpful in the modification of existing BIPs and the development of new interventions to reduce IPV. PMID- 22096017 TI - When can I help? A conceptual framework for the prevention of sexual violence through bystander intervention. AB - The bystander intervention approach is gaining popularity as a means for engaging communities in sexual assault prevention, especially on college campuses. Many bystander programs are teaching community members how to intervene without first assisting them to identify the full range of opportunities when they can intervene. In this article, the authors review the literature on sexual violence bystander intervention and present a conceptual framework that lays out a continuum of bystander opportunities ranging from reactive situations after an assault has occurred, to situations before an assault has occurred (posing high to low risk to victims), as well as proactive situations where no risk to the victim is present. The implications of this typology are discussed in the context of program development, evaluation, and further research. PMID- 22096018 TI - Production of artificial piRNAs in flies and mice. AB - In animals a discrete class of small RNAs, the piwi-interacting RNAs (piRNAs), guard germ cell genomes against the activity of mobile genetic elements. piRNAs are generated, via an unknown mechanism, from apparently single-stranded precursors that arise from discrete genomic loci, termed piRNA clusters. Presently, little is known about the signals that distinguish a locus as a source of piRNAs. It is also unknown how individual piRNAs are selected from long precursor transcripts. To address these questions, we inserted new artificial sequence information into piRNA clusters and introduced these marked clusters as transgenes into heterologous genomic positions in mice and flies. Profiling of piRNA from transgenic animals demonstrated that artificial sequences were incorporated into the piRNA repertoire. Transgenic piRNA clusters are functional in non-native genomic contexts in both mice and flies, indicating that the signals that define piRNA generative loci must lie within the clusters themselves rather than being implicit in their genomic position. Comparison of transgenic animals that carry insertions of the same artificial sequence into different ectopic piRNA-generating loci showed that both local and long-range sequence environments inform the generation of individual piRNAs from precursor transcripts. PMID- 22096019 TI - What color is the skin of a mouse? PMID- 22096021 TI - Current parathyroid hormone immunoassays do not adequately meet the needs of patients with chronic kidney disease. AB - BACKGROUND: There are significant differences in plasma parathyroid hormone (PTH) results obtained by current immunoassay methods. However, many clinical guidelines relevant to patients with chronic kidney disease (CKD) that recommend PTH target values do not take account of these differences. This raises major questions about the validity of the evidence underpinning current use of PTH measurements in the management of CKD as well as of published relevant audit data. METHODS: PTH was measured in plasma from patients with CKD in six commercially available immunoassays. The initial pilot study included 19 patients while 98 patients were included in a second extended study. Data from the second study were analysed by regression analysis to obtain assay-specific targets for each immunoassay. RESULTS: Although similar PTH reference intervals are provided by most manufacturers, both studies confirmed substantial between-method differences in observed PTH for all patients, with results varying by as much as 4.2-fold between the lowest and highest reading methods. These differences were sufficient to have treatment implications for 79% of the patients in the pilot study. Applying the assay-specific targets derived here to results from the extended study decreased treatment misclassifications from 53% to 12%. CONCLUSIONS: Existing between-method differences in PTH measurements clearly have treatment implications. International initiatives to address these differences are in progress and will require support and input from all stakeholders. Adoption of assay-specific target values such as those reported here provides a convenient and practical interim solution that should lead to significant improvement in patient management, while also enabling meaningful audit. PMID- 22096022 TI - Cell phone is best emergency link with GPs. PMID- 22096024 TI - Lymphatic invasion is independently prognostic of metastasis in primary cutaneous melanoma. AB - PURPOSE: Lymphatic invasion (LI) in primary cutaneous melanomas was recently found to be common. In this study, we evaluated LI as an independent prognostic factor. EXPERIMENTAL DESIGN: This study included 251 patients with vertical growth phase (VGP) primary cutaneous melanomas who had paraffin-fixed lesional tissue and were in a prospective cohort seen between 1972 and 1991, had no clinical evidence of regional nodal disease at diagnosis, and had at least ten years of follow-up. Dual immunohistochemical staining was used to detect lymphatic endothelium (podoplanin) and melanoma cells (S-100). Multivariate logistic regression for ten-year metastasis was used to define independent prognostic factors, and a prognostic tree was developed to characterize and discriminate risk groups. Kaplan-Meier disease-free survival curves for those with and without LI within current American Joint Committee on Cancer stages were compared using the log-rank statistic. RESULTS: LI was observed in 43% (108 of 251) of the study melanomas. The multivariate model for ten-year metastasis identified four independent prognostic factors: tumor thickness, mitotic rate, LI, and anatomic site. The prognostic tree identified a group of patients with thin (<=1 mm thick) melanomas and poor prognosis: stage IB melanomas with LI. Survival curves for time to first metastasis showed significantly poorer prognosis for patients with LI compared with those without it for both stages IB and IIA. CONCLUSIONS: LI is common across the range of tumor thicknesses in primary VGP melanomas. It is an independent prognostic factor and significantly increases the risk of metastasis in patients in clinical stages IB and IIA. PMID- 22096023 TI - Prognostic significance of plasma osteopontin in patients with locoregionally advanced head and neck squamous cell carcinoma treated on TROG 02.02 phase III trial. AB - PURPOSE: High plasma osteopontin (OPN) levels have been reported to be an adverse prognostic factor in head and neck squamous cell carcinomas (HNSCC), correlate with tumor hypoxia, and be predictive of benefit from hypoxia-targeted therapy. We sought to confirm the prognostic and predictive significance of OPN in patients treated on a large international trial. EXPERIMENTAL DESIGN: Patients with stage III/IV HNSCC were randomized to receive definitive radiotherapy concurrently with cisplatin or cisplatin plus the hypoxic cell cytotoxin, tirapazamine (TPZ). Eligibility criteria for this prospective substudy included plasma sample availability for OPN assay by ELISA and absence of major radiation therapy deviations (N = 578). OPN concentrations were analyzed for overall survival (OS) and time to locoregional failure (TTLRF), adjusting for known prognostic factors. Additional analysis was carried out in patients with available tumor p16(INK4A) staining status. RESULTS: The median OPN level was 544 ng/mL (range: 7-2,640). High OPN levels were not associated with worse OS (relative HR, 1.03 for highest tertile) or TTLRF (relative HR 0.91 for highest tertile). There was no interaction between OPN and treatment arm for OS or TTLRF (P = 0.93 for OS; P = 0.87 for TTLRF). For the highest tertile the 2-year OS was 66% on control arm and 67% on TPZ arm (HR = 1.11, P = 0.67). Similarly for p16(INK4A) negative patients in the highest tertile, the 2-year OS was 61% on control arm and 63% on TPZ arm (HR = 1.05, P = 0.86). CONCLUSIONS: We found no evidence that high plasma OPN levels were associated with an adverse prognosis in HNSCC, or were predictive of benefit with hypoxia targeting therapy. PMID- 22096025 TI - Skin tumors induced by sorafenib; paradoxic RAS-RAF pathway activation and oncogenic mutations of HRAS, TP53, and TGFBR1. AB - PURPOSE: The emergence of skin tumors in patients treated with sorafenib or with more recent BRAF inhibitors is an intriguing and potentially serious event. We carried out a clinical, pathologic, and molecular study of skin lesions occurring in patients receiving sorafenib. EXPERIMENTAL DESIGN: Thirty-one skin lesions from patients receiving sorafenib were characterized clinically and pathologically. DNA extracted from the lesions was screened for mutation hot spots of HRAS, NRAS, KiRAS, TP53, EGFR, BRAF, AKT1, PI3KCA, TGFBR1, and PTEN. Biological effect of sorafenib was studied in vivo in normal skin specimen and in vitro on cultured keratinocytes. RESULTS: We observed a continuous spectrum of lesions: from benign to more inflammatory and proliferative lesions, all seemingly initiated in the hair follicles. Eight oncogenic HRAS, TGFBR1, and TP53 mutations were found in 2 benign lesions, 3 keratoacanthomas (KA) and 3 KA-like squamous cell carcinoma (SCC). Six of them correspond to the typical UV signature. Treatment with sorafenib led to an increased keratinocyte proliferation and a tendency toward increased mitogen-activated protein kinase (MAPK) pathway activation in normal skin. Sorafenib induced BRAF-CRAF dimerization in cultured keratinocytes and activated CRAF with a dose-dependent effect on MAP-kinase pathway activation and on keratinocyte proliferation. CONCLUSION: Sorafenib induces keratinocyte proliferation in vivo and a time- and dose-dependent activation of the MAP kinase pathway in vitro. It is associated with a spectrum of lesions ranging from benign follicular cystic lesions to KA like SCC. Additional and potentially preexisting somatic genetic events, like UV induced mutations, might influence the evolution of benign lesions to more proliferative and malignant tumors. PMID- 22096026 TI - EpCAM/CD3-Bispecific T-cell engaging antibody MT110 eliminates primary human pancreatic cancer stem cells. AB - PURPOSE: Tumor-initiating cells with stem-like properties, also termed cancer stem cells (CSC), have been shown to sustain tumor growth as well as metastasis and are highly resistant to chemotherapy. Because pancreatic CSCs have been isolated on the basis of EpCAM expression, we investigated whether a targeted immunotherapy to EpCAM using the bispecific T-cell-engaging antibody MT110 is capable of eradicating CSCs. EXPERIMENTAL DESIGN: We studied in vitro and in vivo the effects of MT110 on CSCs using both established cell lines as well as primary cells of human pancreatic cancer. RESULTS: Although established cell lines were more responsive to MT110-engaged T cells, also primary cells showed a time- and dose-dependent response to treatment with the bispecific antibody. In addition, the population of highly tumorigenic CSCs was efficiently targeted by the EpCAM/CD3-bispecific antibody MT110 in vitro and in vivo using a mouse model of established primary pancreatic cancer. Pancreatic cancer cells derived from metastases were slightly more resistant to MT110 treatment on the basis of in vivo tumorigenicity studies. This appeared to be related to a higher frequency of an EpCAM-negative subpopulation of CSCs. CONCLUSIONS: Cytotoxic T cells can be effectively redirected against primary human pancreatic cancer cells by T-cell engaging BiTE antibody MT110 including a subpopulation of highly tumorigenic CSCs. PMID- 22096029 TI - Control of glycolysis through regulation of PFK1: old friends and recent additions. AB - Regulation of glucose metabolism is a crucial aspect of cell physiology in normal and disease conditions. Many regulatory events are involved in determining the metabolic fate of glucose and the pathways into which it is directed. The first reaction that commits glucose to the glycolytic pathway is catalyzed by the enzyme phosphofructokinase-1 (PFK-1) and is tightly regulated. One of the most potent activators of PFK-1 is fructose 2,6 bisphosphate (F2,6BP) and its cellular levels are correlated with glycolytic flux. F2,6BP is synthesized and degraded by a family of bifunctional enzymes-the 6-phosphofructo-2-kinase/fructose-2,6 bisphosphatases (PFKFB). The interplay among F2,6BP levels, the enzymes that generate and degrade it, and PFK-1 activity has important consequences for several different aspects of cell metabolism as well as for systemic metabolic conditions. TIGAR, a recently identified F2,6 bisphosphatase (F2,6BPase), could also contribute to this complexity and participate in shaping the metabolic profile of the cell. PMID- 22096028 TI - Transcriptional control of cardiac fuel metabolism and mitochondrial function. AB - As a persistent pump, the mammalian heart demands a high-capacity mitochondrial system. Significant progress has been made in delineating the gene regulatory networks that control mitochondrial biogenesis and function in striated muscle. The PPARgamma coactivator-1 (PGC-1) coactivators serve as inducible boosters of downstream transcription factors that control the expression of genes involved in mitochondrial energy transduction, ATP synthesis, and biogenesis. PGC-1 gain-of function and loss-of-function studies targeting two PGC-1 family members, PGC 1alpha and PGC-1beta, have provided solid evidence that these factors are both necessary and sufficient for perinatal mitochondrial biogenesis and maintenance of high-capacity mitochondrial function in postnatal heart. In humans, during the development of heart failure owing to hypertension or obesity-related diabetes, the activity of the PGC-1 coactivators, and several downstream target transcription factors, is altered. Gene targeting studies in mice have demonstrated that loss of PGC-1alpha and PGC-1beta in heart leads to heart failure. Interestingly, the pattern of dysregulation within the PGC-1 transcriptional regulatory circuit distinguishes the heart disease caused by hypertension from that caused by diabetes. This transcriptional regulatory cascade and downstream metabolic pathways should be considered as targets for novel etiology-specific therapeutics aimed at the early stages of heart failure. PMID- 22096027 TI - A noncanonical Flt3ITD/NF-kappaB signaling pathway represses DAPK1 in acute myeloid leukemia. AB - PURPOSE: Death-associated protein kinase 1 (DAPK1), a tumor suppressor, is a rate limiting effector in an endoplasmic reticulum (ER) stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of acute myeloid leukemia (AML) with poor prognosis, which lacked ER stress-induced apoptosis. EXPERIMENTAL DESIGN: Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-kappaB-and c-Jun-responsive genes, was studied. RNA interference knockdown studies were carried out in an Flt3ITD(+) cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1 DAPK1 repression, and chromatin immunoprecipitations were carried out to identify proximate effector proteins, including TAK1-activated p52NF-kappaB, at the DAPK1 locus. RESULTS: AMLs characterized by normal karyotype with Flt3ITD were found to have 10- to 100-fold lower DAPK1 transcripts normalized to the expression of c Jun, a transcriptional activator of DAPK1, as compared with a heterogeneous cytogenetic category. In addition, Meis1, a c-Jun-responsive adverse AML prognostic gene signature was measured as control. These Flt3ITD(+) AMLs overexpress relB, a transcriptional repressor, which forms active heterodimers with p52NF-kappaB. Chromatin immunoprecipitation assays identified p52NF-kappaB binding to the DAPK1 promoter together with histone deacetylase 2 (HDAC2) and HDAC6 in the Flt3ITD(+) human AML cell line MV-4-11. Knockdown of p52NF-kappaB or its upstream regulator, NF-kappaB-inducing kinase (NIK), de-repressed DAPK1. DAPK1-repressed primary Flt3ITD(+) AMLs had selective nuclear activation of p52NF kappaB. CONCLUSIONS: Flt3ITD promotes a noncanonical pathway via TAK1 and p52NF kappaB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD(+) AML. PMID- 22096030 TI - Regulation of glycolysis and gluconeogenesis by acetylation of PKM and PEPCK. AB - Glycolysis is a catabolic process of glucose hydrolysis needed for energy and biosynthetic intermediates, whereas gluconeogenesis is a glucose production process important for maintaining blood glucose levels during starvation. Although they share many enzymes, these two processes are not simply the reverse of each other and are instead reciprocally regulated. Two key enzymes that regulate irreversible steps in these two processes are pyruvate kinase (PK) and phosphoenolpyruvate carboxy kinase (PEPCK), which catalyze the last and first step of glycolysis and gluconeogenesis, respectively, and are both regulated by lysine acetylation. Acetylation at Lys305 of the PKM (muscle form of PK) decreases its activity and also targets it for chaperone-mediated autophagy and subsequent lysosome degradation. Acetylation of PEPCK, on the other hand, targets it for ubiquitylation by the HECT E3 ligase, UBR5/EDD1, and subsequent proteasomal degradation. These studies established a model in which acetylation regulates metabolic enzymes via different mechanisms and also revealed cross talk between acetylation and ubiquitination. Given that most metabolic enzymes are acetylated, we propose that acetylation is a major posttranslational modifier that regulates cellular metabolism. PMID- 22096032 TI - The challenges and concerns companies face pertaining to the US Food and Drug Administration 510(k) process for cardiac biomarkers. PMID- 22096033 TI - Assessment of carotid plaque stability based on the dynamic enhancement pattern in plaque components with multidetector CT angiography. AB - BACKGROUND AND PURPOSE: Recent studies have investigated plaque morphology to determine patients who are at high risk of carotid atherosclerosis. In this study, we investigated whether a difference in dynamic enhancement pattern in plaque components could be useful to assess plaque stability with multidetector CT angiography. METHODS: Fifty-nine lesions with moderate to severe carotid atherosclerosis in 51 patients (33 symptomatic, 18 asymptomatic) were consecutively included. Early- and delayed-phase images were obtained in 3 equivalent axial slices with multidetector CT angiography. Hounsfield units (HU) in the early phase were subtracted from those in the delayed phase in plaques (DeltaHU) and compared with clinical features, MRI-based plaque characteristics, and histological findings with 20 surgical specimens acquired from carotid endarterectomy. RESULTS: The DeltaHU was significantly higher in asymptomatic than that in symptomatic presentation (P=0.02). With MRI, a higher DeltaHU was negatively correlated with signal intensity on T1-weighted imaging (r=-0.56, P<0.0001). Histology confirmed that DeltaHU was positively correlated with fibrous tissue (r=0.67, P=0.001) and negatively correlated with a lipid-rich necrotic core with hemorrhage (r=-0.70, P<0.001). Moreover, less neovascularization and inflammation was found in plaques with a higher DeltaHU. CONCLUSIONS: Delayed-phase images provide information regarding the dynamic change in contrast media from the early arterial phase. An increase in HU from the early phase on multidetector CT angiography indicates plaque stability with more fibrous tissue and a less lipid-rich necrotic core, intraplaque hemorrhage, and neovascularization. PMID- 22096031 TI - Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial. AB - OBJECTIVE: We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial. BACKGROUND: Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE ACS. METHODS: We measured ST2 with a high-sensitivity assay in all available baseline samples (N=4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee. RESULTS: Patients with ST2 concentrations in the top quartile (>35 MUg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P<0.0001) and 1 year (12.2% vs 5.2%, P<0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15-3.13 at 30 days, P=0.012; 1.51, 95% CI 1.15-1.98 at 1 year, P=0.003), with a significant integrated discrimination improvement (P<0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction=0.15). CONCLUSIONS: ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling. PMID- 22096034 TI - Levodopa treatment improves functional recovery after experimental stroke. AB - BACKGROUND AND PURPOSE: Delayed treatment of patients with stroke with levodopa/benserazide contributes to enhanced functional recovery, but the mechanisms involved are poorly understood. The present study was designed to investigate if levodopa/benserazide treatment improves recovery of lost neurological function and contributes to tissue reorganization in the rat brain after stroke. METHODS: Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (120 minutes) and treated with levodopa (1, 5, and 20 mg/kg)/benserazide (15 mg/kg) or saline for 12 consecutive days starting on Day 2 after transient occlusion of the middle cerebral artery. Infarct volume was determined and sensorimotor function was assessed using the rotating pole test, a 28-point neuroscore, and a cylinder test on Days 2, 7, and 14 after transient occlusion of the middle cerebral artery. The spatiotemporal expression pattern of dopamine-1 and dopamine-2 receptors and the dopamine- and cAMP-regulated neuronal phosphoprotein in reactive astrocytes were analyzed in the ischemic hemisphere as well as in cultured astrocytes. RESULTS: Treatment with levodopa/benserazide significantly improved the recovery of sensorimotor function after transient occlusion of the middle cerebral artery without affecting the infarct volume. In addition, we found that different subpopulations of glial fibrillary acidic protein-positive astrocytes in the peri-infarct area express dopamine-1 receptors and dopamine-2 receptors as well as dopamine- and cAMP-regulated neuronal phosphoprotein. CONCLUSIONS: Our results strongly corroborate the concept of recovery enhancing actions of levodopa treatment after stroke. Also, astrocytes in the peri-infarct area may contribute to the dopamine enhanced recovery mechanisms. PMID- 22096035 TI - Sulcal effacement on fluid attenuation inversion recovery magnetic resonance imaging in hyperacute stroke: association with collateral flow and clinical outcomes. AB - BACKGROUND AND PURPOSE: The clinical significance of sulcal effacement has been widely investigated in CT studies, but the results are controversial. In this study, we evaluated the presence of perisylvian sulcal effacement (PSE) on fluid attenuation inversion recovery MRI and hypothesized that PSE may be related to collateral flow status together with hyperintense vessels on fluid attenuation inversion recovery in hyperacute stroke. In addition, we investigated whether an association between PSE and clinical outcome could be found in these patients. METHODS: Consecutive patients with acute middle cerebral artery infarcts within 6 hours of symptom onset were included. All patients had internal carotid artery or middle cerebral artery occlusion and underwent MRI including FLAIR. The presence of PSE and hyperintense vessels on fluid attenuation inversion recovery and the collateral status and occurrence of early recanalization (ER) on conventional angiography were evaluated. RESULTS: Of 139 patients, 79 (56.8%) had PSE. Multivariate testing revealed PSE was independently associated with collateral status. The association between hyperintense vessels and collaterals was different depending on PSE. Compared to PSE-positive and ER-negative patients, PSE-negative and ER-negative patients (odds ratio, 4.11; 95% confidence interval, 1.12-15.17) and PSE-negative and ER-positive patients (odds ratio, 34.62; 95% confidence interval, 5.75-208.60), but not PSE-positive and ER-positive patients, were more likely to experience favorable clinical outcomes (modified Rankin Scale score <= 2 at 3 months). CONCLUSIONS: PSE is independently associated with collateral status in patients with acute middle cerebral artery stroke. Moreover, PSE in conjunction with recanalization status can predict clinical outcomes in these patients. PMID- 22096036 TI - Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke. AB - BACKGROUND AND PURPOSE: Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. METHODS: Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. RESULTS: Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. CONCLUSIONS: Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID- 22096038 TI - Traditional urinary biomarkers in the assessment of hospital-acquired AKI. AB - Traditional biomarkers, such as urine chemistries and urine microscopic elements, are used in the diagnosis and care of patients with AKI. Urine chemistries, such as fractional excretion of sodium and fractional excretion of urea, are useful for differentiating prerenal AKI from acute tubular necrosis only in select patients. Urine microscopy using a quantitative evaluation of the urine sediment for renal tubular epithelial cells, renal tubular epithelial cell casts, and granular casts has recently been shown to differentiate prerenal AKI from acute tubular necrosis and also provide prognostic information. Urine microscopy has also been noted to compare favorably with new urine biomarkers for diagnosis and prognosis of AKI. Thus, current information on urine diagnostics suggests that urine chemistries have a limited role in differential diagnosis of AKI, whereas urine microscopy and new urine biomarkers may be used together to differentiate prerenal AKI from acute tubular necrosis and predict such outcomes as worsened AKI, acute dialysis, and death. PMID- 22096037 TI - Timing and determinants of erythropoietin deficiency in chronic kidney disease. AB - BACKGROUND AND OBJECTIVES: Anemia in patients with CKD is highly related to impaired erythropoietin (EPO) response, the timing and determinants of which remain unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study measured EPO levels and studied their relation to GFR measured by 51Cr-EDTA renal clearance (mGFR) in 336 all-stage CKD patients not receiving any erythropoiesis stimulating agent. RESULTS: In patients with anemia defined by World Health Organization criteria (hemoglobin [Hb] <13 g/dl in men and 12 g/dl in women), EPO response to Hb level varied by mGFR level. EPO and Hb levels were negatively correlated (r=-0.22, P=0.04) when mGFR was >30 ml/min per 1.73 m(2), whereas they were not correlated when mGFR was <30 (r=0.09, P=0.3; P for interaction=0.01). In patients with anemia, the ratio of observed EPO to the level predicted by the equation for their Hb level decreased from 0.72 (interquartile range, 0.57-0.95) for mGFR >=60 ml/min per 1.73 m(2) to 0.36 (interquartile range, 0.16-0.69) for mGFR <15. Obesity, diabetes with nephropathy other than diabetic glomerulopathy, absolute iron deficiency, and high C-reactive protein concentrations were associated with increased EPO levels, independent of Hb and mGFR. CONCLUSIONS: Anemia in CKD is marked by an early relative EPO deficiency, but several factors besides Hb may persistently stimulate EPO synthesis. Although EPO deficiency is likely the main determinant of anemia in patients with advanced CKD, the presence of anemia in those with mGFR >30 ml/min per 1.73 m(2) calls for other explanatory factors. PMID- 22096039 TI - AKI associated with macroscopic glomerular hematuria: clinical and pathophysiologic consequences. AB - Hematuria is a common finding in various glomerular diseases. This article reviews the clinical data on glomerular hematuria and kidney injury, as well as the pathophysiology of hematuria-associated renal damage. Although glomerular hematuria has been considered a clinical manifestation of glomerular diseases without real consequences on renal function and long-term prognosis, many studies performed have shown a relationship between macroscopic glomerular hematuria and AKI and have suggested that macroscopic hematuria-associated AKI is related to adverse long-term outcomes. Thus, up to 25% of patients with macroscopic hematuria-associated AKI do not recover baseline renal function. Oral anticoagulation has been associated with glomerular macrohematuria-related kidney injury. Several pathophysiologic mechanisms may account for the tubular injury found on renal biopsy specimens. Mechanical obstruction by red blood cell casts was thought to play a role. More recent evidence points to cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells. These mechanisms of injury may be shared with hemoglobinuria or myoglobinuria-induced AKI. Heme oxygenase catalyzes the conversion of heme to biliverdin and is protective in animal models of heme toxicity. CD163, the recently identified scavenger receptor for extracellular hemoglobin, promotes the activation of anti-inflammatory pathways, opening the gates for novel therapeutic approaches. PMID- 22096040 TI - The effect of high-flux hemodialysis on hemoglobin concentrations in patients with CKD: results of the MINOXIS study. AB - BACKGROUND AND OBJECTIVES: Hemodialysis treatment induces markers of inflammation and oxidative stress, which could affect hemoglobin levels and the response to erythropoietin use. This study sought to determine whether high-flux dialysis would help improve markers of renal anemia, inflammation, and oxidative stress compared with low-flux dialysis. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: In a prospective, controlled study, 221 patients undergoing maintenance hemodialysis and receiving darbepoetin-alfa treatment (mean age, 66 years; 55% male) from 19 centers were screened in a 20-week run-in period of low-flux hemodialysis with a synthetic dialysis membrane. Thereafter, 166 patients were enrolled and randomly assigned to receive a synthetic high-flux membrane or to continue on low-flux dialysis for 52 weeks. Data on myeloperoxidase, oxidized LDL, high-sensitivity C-reactive protein, and the Malnutrition Inflammation Score were collected at baseline and after 52 weeks; routine laboratory data, such as hemoglobin, ferritin, and albumin, and the use of darbepoetin-alfa, were also measured in the run-in period. Results After 52 weeks, the low-flux and the high flux groups did not differ with respect to hemoglobin (mean +/- SD, 11.7+/-0.9 g/dl versus 11.7+/-1.1 g/dl; P=0.62) or use of darbepoetin-alfa (mean dosage +/- SD, 29.8+/-24.8 MUg/wk versus 26.0+/-31.1 MUg/wk; P=0.85). Markers of inflammation, oxidative stress, or nutritional status also did not differ between groups. CONCLUSION: Over 1 year, high-flux dialysis had no superior effects on hemoglobin levels or markers of inflammation, oxidative stress, and nutritional status. These data do not support the hypothesis that enhanced convective toxin removal would improve patient outcome. PMID- 22096041 TI - Seasonal variations in mortality, clinical, and laboratory parameters in hemodialysis patients: a 5-year cohort study. AB - BACKGROUND AND OBJECTIVES: Mortality varies seasonally in the general population, but it is unknown whether this phenomenon is also present in hemodialysis patients with known higher background mortality and emphasis on cardiovascular causes of death. This study aimed to assess seasonal variations in mortality, in relation to clinical and laboratory variables in a large cohort of chronic hemodialysis patients over a 5-year period. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study included 15,056 patients of 51 Renal Research Institute clinics from six states of varying climates in the United States. Seasonal differences were assessed by chi-squared tests and univariate and multivariate cosinor analyses. RESULTS: Mortality, both all-cause and cardiovascular, was significantly higher during winter compared with other seasons (14.2 deaths per 100 patient-years in winter, 13.1 in spring, 12.3 in autumn, and 11.9 in summer). The increase in mortality in winter was more pronounced in younger patients, as well as in whites and in men. Seasonal variations were similar across climatologically different regions. Seasonal variations were also observed in neutrophil/lymphocyte ratio and serum calcium, potassium, and platelet values. Differences in mortality disappeared when adjusted for seasonally variable clinical parameters. CONCLUSIONS: In a large cohort of dialysis patients, significant seasonal variations in overall and cardiovascular mortality were observed, which were consistent over different climatic regions. Other physiologic and laboratory parameters were also seasonally different. Results showed that mortality differences were related to seasonality of physiologic and laboratory parameters. Seasonal variations should be taken into account when designing and interpreting longitudinal studies in dialysis patients. PMID- 22096042 TI - Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens. AB - Fosfomycin has attracted renewed interest for the treatment of lower urinary tract and even systemic infections caused by Gram-negative pathogens with resistance to traditionally used agents. The main concern regarding the clinical utility of fosfomycin refers to the potential for the emergence of resistance during therapy. In this review, we evaluate the available published evidence regarding the mechanisms and the frequency of in vitro mutational resistance to fosfomycin in Gram-negative pathogens. We also review data regarding the emergence of resistance in clinical studies of fosfomycin therapy in various infectious syndromes and data from studies that evaluate the evolution of fosfomycin resistance over time. There appears to be discordance between the high frequency of mutational resistance to fosfomycin in vitro and the lower extent of this phenomenon in clinical studies. This discordance could at least partly be attributed to a biological cost associated with common mutations that confer resistance to fosfomycin, including decreased growth rate and low adherence to epithelial cells for the resistant mutants. The development of resistance appears to be more frequent both in vitro and in clinical studies for Pseudomonas aeruginosa in comparison with Escherichia coli, whereas relevant data for other Enterobacteriaceae are relatively scarce. The urinary tract seems to provide a favourable environment for the use of fosfomycin with a low associated likelihood for the emergence of resistance, owing to high drug concentrations and acidic pH. Additional data are needed to further clarify the optimal use of fosfomycin for different infectious syndromes caused by contemporary multidrug-resistant pathogens. PMID- 22096043 TI - A novel phenicol exporter gene, fexB, found in enterococci of animal origin. AB - OBJECTIVES: To investigate two porcine Enterococcus isolates for the genetic basis of phenicol resistance and to determine the location and the genetic environment of the novel resistance gene. METHODS: A total of 391 isolates with reduced florfenicol susceptibility (MIC >= 16 mg/L), obtained from 557 nasal swabs of individual pigs, were screened by PCR for the known florfenicol resistance genes. Isolates that were negative in these PCRs were analysed for their species assignment and antimicrobial susceptibility. Plasmids were extracted and subjected to transformation and conjugation assays. Restriction fragments of the phenicol resistance plasmids were cloned and sequenced. The sequences obtained were analysed and compared with sequences deposited in the databases. RESULTS: The two isolates, Enterococcus faecium EFM-1 and Enterococcus hirae EH-1, exhibited MICs of chloramphenicol and florfenicol of 64 mg/L and carried a new phenicol resistance gene, designated fexB. This gene codes for a phenicol exporter of 469 amino acids organized in 14 transmembrane domains. The fexB gene was located on the 35 kb pEFM-1 from E. faecium and on the 25.3 kb pEH 1 from E. hirae, respectively. Both plasmids were non-conjugative. The fexB gene was found to be embedded in virtually the same genetic environment of 14.8 kb in both plasmids. CONCLUSION: To the best of our knowledge, this is the first report of the new florfenicol exporter gene fexB. Based on its plasmid location, horizontal transfer from the enterococci to other bacteria is possible. PMID- 22096044 TI - Emerging HIV-1 resistance to tipranavir and darunavir in patients with virological failure to first-generation protease inhibitors in Taiwan. AB - Ritonavir-boosted tipranavir (TPV/r) and darunavir (DRV/r) have been approved in patients with virological resistance to multiple protease inhibitors (PIs). Whether the HIV-1 from these patients with virological failure to first generation PIs remains susceptible to TPV/r or DRV/r is questionable. The susceptibilities of HIV-1 isolates to second-generation PIs in patients who experienced virological failure in three time periods were analysed: 9-2006 to 4 2007 (period 1), 5-2007 to 12-2007 (period 2) and 1-2008 to 8-2008 (period 3). A total of 53 subjects were enrolled, and 51 subject isolates (96.2%) were resistant to >=1 PIs. The mutation scores for TPV and DRV, and the percentage of isolates with resistance to TPV or DRV, increased significantly from period 1 to period 3. Our data revealed a significant increase in the levels of genotypic resistance to TPV and DRV over the past two years in patients with virological failure to first-generation PIs. PMID- 22096045 TI - Enrolment and programmatic trends and predictors of antiretroviral therapy initiation from president's emergency plan for AIDS Relief (PEPFAR)-supported public HIV care and treatment sites in rural Mozambique. AB - Many countries in sub-Saharan Africa have made antiretroviral therapy (ART) available in urban settings, but the progress of treatment expansion into rural Africa has been slower. We analysed routine data for patients enrolled in a rural HIV treatment programme in Zambezia Province, Mozambique (1 June 2006 through 30 March 2009). There were 12,218 patients who were >=15 years old enrolled (69% women). Median age was 25 years for women and 31 years for men. Older age and higher level of education were strongly predictive of ART initiation (P < 0.001). Patients with a CD4+ count of 350 cells/MUL versus 50 cells/MUL were less likely to begin ART (odds ratio [OR]: 0.19, 95% confidence interval [CI]: 0.16-0.23). In rural sub-Saharan Africa, HIV testing, linkage to care, logistics for ART initiation and fears among some patients to take ART require specialized planning to maximize successes. Sustainability will require improved health manpower, infrastructure, stable funding, continuous drug supplies, patient record systems and, most importantly, community engagement. PMID- 22096046 TI - A prognostic scoring tool for identification of patients at high and low risk of death from HIV-associated Pneumocystis jirovecii pneumonia. AB - A prognostic scoring tool (PST) was created to aid prediction of outcome from HIV associated Pneumocystis jirovecii pneumonia (PCP) using data obtained from 577 episodes of PCP among 540 patients presenting to a specialist HIV treatment centre in London, UK. It used risk factors identifiable at/soon after hospitalization, previously identified as being associated with mortality: repeat episode of PCP, patient's age, haemoglobin (Hb) and oxygen partial pressure (PaO(2)) on admission, presence of medical co-morbidity (Comorb) and of pulmonary Kaposi sarcoma (PKS). The derived PST was 25.5+(age in years/10) + 2 (if a repeat episode of PCP) + 3 (if Comorb present) + 4 (if PKS detected) - PaO(2) (kPa) - Hb (g/dL), and produced scores that ranged between 0 and 19. Patients were divided into five groups according to their prognostic score: 0-3.9 = group 1 (0% mortality), 4-7.9 = group 2 (3% mortality), 8-10.9 = group 3 (9% mortality), 11 14.9 = group 4 (29% mortality) and >= 15 = group 5 (52% mortality). This PST facilitates rapid identification of patients early in their hospitalization who have mild or severe HIV-associated PCP and who are at high and low risk of in hospital death from PCP. The PST may aid assessment of severity of illness and in directing treatment strategies, but requires validation in patient cohorts from other health-care institutions. PMID- 22096047 TI - Young adults' preferred options for receiving chlamydia screening test results: a cross-sectional survey of 6085 young adults. AB - We investigated how young adults aged 18-29 years would like to be notified of chlamydia screening test results, and, when they test positive, their willingness and preferred mechanism for informing their partners. We conducted a cross sectional survey of 6085 young adults and found that a call to their mobile phone was their preferred way of receiving positive test results (selected by 50%), followed by email. Text messages (short message service [SMS]) and calls to landline phones were unpopular options, selected by between 5 and 10%. Over 75% of respondents stated they would inform their current partner of a positive chlamydia diagnosis, and 50% would inform their previous partners. Most were willing to receive yearly reminders to go for a chlamydia test. Young adults preference for being informed of chlamydia test results by mobile phone call, rather than by email or SMS text, especially if they test positive, suggests they place high value on the security of the communication mechanism. Offering a range of mechanisms for receipt of test results may increase the acceptability and coverage of sexually transmitted infection (STI) control strategies. PMID- 22096048 TI - Factors associated with repeat visits among clients attending a clinic for sexually transmitted infections in Kisumu, Kenya. AB - To identify factors associated with repeat visits among patients attending a clinic for sexually transmitted infections (STIs) in Kisumu, Kenya, we examined records of clinic visits from March 2009 to May 2010. Multivariable logistic regression identified factors associated with repeat visits occurring >30 days after the initial visit. Among 1473 clients (1296 single-visit individuals versus 177 individuals with repeat visits), the median age was 24 years, 67% were men and 8.6% self-reported being HIV-positive. In adjusted analyses, men with repeat visits were more likely to report >= 2 recent sexual partners (adjusted odds ratio [aOR] = 1.60) and being HIV-positive (aOR = 2.35). They were less likely to have been referred from other health facilities (aOR = 0.14) and more likely to have urethral discharge at their initial visit (aOR = 2.46). Among women, repeat visits were associated with vaginal discharge (aOR = 2.22), but attending the clinic with a partner was protective (aOR = 0.38). The association between sexual risk, HIV positivity and repeat visits among male clients highlights the need to focus intervention efforts on this group. For women, attending with a partner may reflect a decreased risk of re-infection if both partners are treated and counselled together. PMID- 22096050 TI - Particular clinical presentations of psoriasis in HIV patients. AB - Patients with HIV infection have a higher propensity for infectious, inflammatory, neoplastic and metabolic disorders. The link with psoriasis vulgaris is explained by well-known pathophysiological phenomena and can be observed at any stage of infection. The aim of our study was to characterize the clinical spectrum of psoriasis in a group of 50 patients with HIV. Our findings showed particular clinical presentations of psoriasis in those patients, suggesting a predilection for scalp lesions, palmoplantar keratoderma and flexural involvement, as well as a trend towards severe immunodeficiency. Psoriasis, a frequent reason for consultation, allows earlier suspicion and diagnosis of HIV in the presence of these particular patterns. PMID- 22096049 TI - Impact of international laboratory partnerships on the performance of HIV/sexually transmitted infection testing in five resource-constrained countries. AB - To review a quality control and quality assurance (QC/QA) model established to ensure the validity and reliability of collection, storage and analysis of biological outcome data, and to promote good laboratory practices (GLPs) and sustained operational improvements in international clinical laboratories, we conducted a two-arm randomized community-level HIV behavioural intervention trial in five countries: China, India, Peru, Russia and Zimbabwe. The trial was based on diffusion theory utilizing a Community Popular Opinion Leaders (CPOLs) intervention model with behavioural and biological outcomes. The QC/QA model was established by the Biological Outcome Workgroup, which collaborated with the Data Coordinating Center and John Hopkins University Reference Laboratory. Five international laboratories conducted chlamydia/gonorrhoea polymerase chain reaction (PRC)-based assays, herpes simplex virus type 2 enzyme immunoassay (EIA), syphilis serology (rapid plasma regain and Treponema pallidum particle agglutination assay, HIV serology (EIA/Western blot) and Trichomonas vaginalis culture. Data were collected at baseline, 12 and 24 months. Laboratory performance and infrastructure improved throughout the trial. Recommendations for improvement were consistently followed. Quality laboratories in resource-poor settings can be established, operating standards can be improved and certification can be obtained with consistent training, monitoring and technical support. Building collaborative partnership relations can establish a sustainable network for clinical trials, and can lead to accreditation and international laboratory development. PMID- 22096051 TI - Oral sex practices, oral human papillomavirus and correlations between oral and cervical human papillomavirus prevalence among female sex workers in Lima, Peru. AB - Few data exist on oral human papillomavirus (HPV) prevalence in female sex workers (FSWs). Information regarding oral sex practices of 185 Peruvian FSWs, 18 26 years of age, was obtained via survey and compared with HPV testing results of oral rinse samples. Oral HPV prevalence was 14/185 (7.6%); four (28.9%) HPV genotypes were carcinogenic. One hundred and eighty-two participants reported having had oral sex; 95% reported condom use during oral sex with clients and 9.5% with partners. Women who had oral sex more than three times with their partners in the past month were more likely to have oral HPV than women who had oral sex three times or less (P = 0.06). Ten (71.4%) women with oral HPV were HPV positive at the cervix; conversely 8.3% of women with cervical HPV were HPV positive in the oral cavity. The prevalence of oral HPV was relatively low, considering the high rates of oral sex practiced by these women. PMID- 22096052 TI - Factors associated with HIV-1 virological failure in an outpatient clinic for HIV infected people in Haiphong, Vietnam. AB - The objective of our study was to investigate factors associated with virological failure in 100 consecutive HIV-1 infected Vietnamese adults who initiated antiretroviral therapy (ART) from June 2007 to June 2008. Data were collected from medical records, and a structured questionnaire was used in individual interviews to investigate factors associated with adherence to ART. Plasma HIV viral load was measured at the time of the interview. The median age was 35 years, 35% were women and heterosexual intercourse was the most common mode of HIV transmission (61%). After a median of 14 months since starting ART, 23% had detectable HIV-1 viral load (>= 400 copies/mL). Patients who had developed a World Health Organization (WHO) clinical stage 4 condition at the time of initiation of ART were more likely to experience virological failure than those in stages 1-3, odds ratio (OR): 5.20 (95% confidence interval [CI] 1.34-20.11), P = 0.017. Patients who reported that their health status was evaluated by a physician at each visit were less likely to experience virological failure, OR: 0.02 (95% CI 0.00-0.24), P = 0.002. PMID- 22096053 TI - Predictors of poor clinical outcome of cryptococcal meningitis in HIV-infected patients. AB - The aim of this study was to identify baseline prognostic factors for poor clinical outcome of HIV-associated cryptococcal meningitis. We conducted a trial in Thailand and the USA comparing low- and high-dose concomitant use of amphotericin B and fluconazole for HIV-associated cryptococcal meningitis to amphotericin B followed by fluconazole. Subjects who were either alive and cerebrospinal fluid (CSF) culture-positive or dead were considered to have a poor outcome. At day 14, baseline characteristics associated with poor outcome included: low weight, high CSF cryptococcal antigen (CrAg) titre and low CSF white blood cell (WBC) count. At day 70, the associated baseline characteristics included: CSF CrAg titre >1:1024 and low Karnofsky performance status. Overall, consistent with published findings, low weight, high CSF CrAg titre and low CSF WBC counts at baseline were predictors for poor clinical outcome. In addition, we found that low Karnofsky performance status was predictive of poor outcome. Prompt management with appropriate antifungal therapy for this particular group of patients may improve the outcomes. PMID- 22096054 TI - An evaluation of the early effects of a combination antiretroviral therapy programme on the management of AIDS-associated Kaposi's sarcoma in KwaZulu-Natal, South Africa. AB - Roll-out of combination antiretroviral therapy (cART) in South Africa should impact on AIDS-associated Kaposi's sarcoma (KS). Government provision began in 2003, with 23% coverage for World Health Organization (WHO) stage IV AIDS in 2006. To assess the effect of cART availability on KS management, we evaluated records from 701 KS patients seen at a tertiary oncology centre in KwaZulu-Natal, South Africa, from 1995 to 2006. Associations between cART use and measures of KS care were evaluated. cART availability was 0% prior to 2001, 9.6% (2001-2003) and 44% (2004-2006). Documentation of HIV status increased incrementally from 65% to 92%. cART was associated with chemotherapy administration: 56% on cART versus 17% not on cART (P < 0.001); and less loss to follow-up, 13% on cART versus 38% not on cART (P < 0.001). cART availability improves the care of AIDS-associated KS. Further increases in cART availability for this population are needed in South Africa. PMID- 22096055 TI - The influence of male circumcision for HIV prevention on sexual behaviour among traditionally circumcised men in Cape Town, South Africa. AB - We examined the relationship between HIV prevention beliefs related to male circumcision and sexual behaviour/sexually transmitted infection (STI) acquisition among traditionally circumcised men in Cape Town, South Africa. HIV negative men (n = 304), circumcised for cultural/religious reasons, attending a health clinic in Cape Town, South Africa, completed cross-sectional surveys. Generalized linear models were used to analyse the relationships between unprotected vaginal sex acts, number of female sexual partners, STI diagnoses and male circumcision-related beliefs and risk perceptions. Men who were aware that circumcision offers protection against HIV (relative risk [RR] = 1.19, 95% confidence interval [CI] = 1.06-1.32, P < 0.01), endorsed risk compensation related to male circumcision (RR = 1.15, 95% CI = 1.11-1.12, P < 0.01) and perceived lower risk of HIV infection when circumcised (RR = 1.08, 95% CI = 1.04 1.12, P < 0.01) were more likely to report unprotected vaginal sex acts. Similar patterns were also identified when predicting number of female sexual partners. Men who were more likely to endorse risk compensation related to male circumcision were also more likely to be diagnosed with a chronic STI (odds ratio [OR] = 1.64, 95% CI = 1.06-2.53, P < 0.05). Our findings suggest that we must not overlook the effects of beliefs towards male circumcision for HIV prevention among men traditionally circumcised; doing so may undermine current efforts to reduce HIV transmission through male circumcision. PMID- 22096056 TI - Microscopy for symptomatic men: not all symptoms are born equal. AB - We reviewed microscopy results for symptomatic male patients in order to identify clinical correlates of urethritis as diagnosed by same-day microscopy. Higher polymorph counts were found in patients presenting with discharge, or discharge together with dysuria, but dysuria without discharge was strongly associated with negative urethral microscopy. Symptoms were strongly linked to microscopy outcome but partnerships were not linked to either symptoms or outcome. PMID- 22096057 TI - Screening for alcohol use disorders in a genitourinary medicine setting. AB - The new National Institute for Health and Clinical Excellence (NICE) guidance cites genitourinary (GU) medicine clinics as one setting where screening for alcohol-use disorders should be part of routine clinical practice. Northumberland GU medicine service has routinely used the Fast Alcohol Screening Tool (FAST) since June 2009. An audit of all first attendees to the service in April 2010 (n = 256) was carried out. This audit found that the FAST questionnaire was acceptable to both patients and staff (uptake of 95.7%). Statistically significant associations between excessive alcohol and higher rates of unprotected sex (P < 0.01), an increased number of sexual partners (P < 0.01) and higher rates of sexually transmitted infection (STI) diagnosis (P < 0.05) were also demonstrated. PMID- 22096058 TI - Audit of receptionists' records of symptoms and concurrence with clinician consultation: data collected for the Department of Health. AB - Audit of reliability of data collected by genitourinary (GU) medicine reception staff in north Cumbria for Department of Health mandatory returns suggests that receptionist-logged presence or absence of symptoms does not concur well with subsequent symptom disclosure to clinicians during consultations, even after the use of patient-completed symptom-specific questionnaires. Triage or fast-tracking based upon symptoms in order to select those at risk of sexually transmitted infection (STI) is likely to fail for a significant proportion of patients. Department of Health symptoms data need to be interpreted with caution. PMID- 22096059 TI - Sexual health of transgender sex workers attending an inner-city genitourinary medicine clinic. AB - Previous studies have reported high HIV prevalence among transgender sex workers (TSWs). We performed a retrospective case-note review of known TSWs attending our unit. In all, 16/24 (66.7%) of patients were diagnosed with at least one sexually transmitted infection (STI) and 7/24 (29.2%) reported intentional unprotected anal or vaginal intercourse, which may explain the high prevalence of HIV in our cohort (37.5%). TSWs disclosed high rates of substance misuse, violence and sexual assault, which may also contribute to the increased prevalence of STI in this group. PMID- 22096060 TI - Acute hepatitis B: the limits of maintaining patient confidentiality. AB - Household contacts of hepatitis B (HBV) are at risk of infection, and guidelines advise vaccination of these contacts in addition to sexual partners (along with traditional high-risk groups). We present a case of intrafamilial transmission of acute hepatitis B virus (HBV) following failure to self-disclose status to family members. Complex confidentiality issues can arise following a diagnosis of HBV infection. PMID- 22096061 TI - HIV-1 clade A infection and viral control: an immunological perspective on a case of underquantification. AB - Although a vast majority of HIV-1-positive patients in the UK are infected with clade B virus, a large number of newly diagnosed cases of heterosexually transmitted HIV-1 are acquired abroad, in countries where non-B clade HIV-1 predominates. Since the development of the viral load assay in 1988, assessment of HIV-1 plasma viraemia has become an integral part of HIV clinical care; however, the contemporary viral load assay was developed and optimized for clade B HIV-1. Here we report the underquantification of viraemia in an individual infected with clade A virus, and the consequent initial classification of the patient as an HIV controller (HIC). Immunological investigations of interferon (IFN)-gamma and lymphoproliferative responses to HIV-1 clade B antigens and peptides, in parallel with mitogenic stimulation, were performed. Subsequent comparison with responses observed within clade B-infected HIC led to viral sequencing, confirmation of infecting clade and recommendation of antiretroviral therapy initiation. We emphasize the growing need for awareness of possible limitations of the commonly used viral load assays, which cannot be relied upon unreservedly in a clinical setting. Furthermore, this case highlights the increasing need for more detailed investigation into both viral genetics and fitness when defining patients as HIC. PMID- 22096062 TI - European Surveillance of Antimicrobial Consumption (ESAC): outpatient penicillin use in Europe (1997-2009). AB - BACKGROUND: Data on 13 years (1997-2009) of outpatient penicillin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project and analysed in detail. METHODS: For the period 1997-2009, data on outpatient use of systemic penicillins aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011) and expressed in DDD per 1000 inhabitants per day (DID). For detailed analysis of trends over time, seasonal variation and composition of outpatient penicillin use in 33 European countries, we distinguished between narrow-spectrum penicillins (NSP), broad-spectrum penicillins (BSP), penicillinase-resistant penicillins (PRP) and combinations with beta-lactamase inhibitors (COP). RESULTS: Total outpatient penicillin (ATC group J01C) use in 2009 varied by a factor of 3.8 between the countries with the highest (16.08 DID in France) and lowest (4.23 DID in the Russian Federation) use. COP represented 45.8%, BSP 40.7%, NSP 10.8% and PRP 2.6% of total European outpatient penicillin use. Total outpatient penicillin use significantly increased over time by 1.53 (SD 0.71) DID between 1997 and 2009. COP (mainly co-amoxiclav) increased by 2.17 (SD 0.40) DID, which was the result of its absolute increase as well as the observed shift from NSP and BSP towards COP. This increase exceeded 10% in 20 countries, where it coincided with a similar decrease in either BSP (15 countries) or NSP (5 countries). CONCLUSIONS: Penicillins represented the most widely used antibiotic subgroup in all 33 participating countries, albeit with considerable variation in their use patterns. For Europe, a continuous increase in overall penicillin use and of COP use was observed during the period 1997-2009. PMID- 22096063 TI - European Surveillance of Antimicrobial Consumption (ESAC): outpatient cephalosporin use in Europe (1997-2009). AB - BACKGROUND: Data on 13 years of outpatient cephalosporin use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC), and analysed in detail. METHODS: For the period 1997-2009, data on outpatient use of systemic cephalosporins aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011) and expressed in DDD per 1000 inhabitants per day (DID). For detailed analysis of trends over time, seasonal variation and composition of outpatient cephalosporin use in 33 European countries, we distinguished between first-generation (J01DB), second-generation (J01DC), third-generation (J01DD) and fourth-generation (J01DE) cephalosporins. RESULTS: Total outpatient cephalosporin use in 2009 varied from 8.7 DID in Greece to 0.03 DID in Denmark. In general, use was higher in Southern and Eastern European countries than in Northern European countries. Total outpatient cephalosporin use increased over time by 0.364 (SD 0.473) DID between 1997 and 2009. Cephalosporin use increased for half of the countries. Low-consuming Northern European countries and the UK further decreased their use. Second generation cephalosporins increased by >20% in seven countries (mainly cefuroxime), coinciding with a decrease in first-generation cephalosporins. Substantial parenteral use of third-generation substances (mainly ceftriaxone) was observed in France, Italy and the Russian Federation. CONCLUSIONS: Since 1997, the use of the older (narrow-spectrum) cephalosporins decreased in favour of the newer (i.e. broad-spectrum) cephalosporins in most countries. Extreme variations between European countries in cephalosporin use over time suggest that they are to a large extent inappropriately used. PMID- 22096064 TI - European Surveillance of Antimicrobial Consumption (ESAC): outpatient antibiotic use in Europe (1997-2009). AB - OBJECTIVES: To describe total outpatient systemic antibiotic use in Europe from 1997 to 2009 and to analyse statistically trends of total use and composition of use over time. METHODS: For the period 1997-2009, data on outpatient use of systemic antibiotics aggregated at the level of the active substance were collected and expressed in defined daily doses (WHO, version 2011) and packages per 1000 inhabitants per day (DID and PID, respectively). Outpatient antibiotic (ATC J01) use in DID in the 33 European countries able to deliver valid data was analysed using longitudinal and compositional data analyses. RESULTS: Total outpatient antibiotic use in 2009 varied by a factor of 3.8 between the countries with the highest (38.6 DID in Greece) and lowest (10.2 DID in Romania) use. For Europe, a significant increase was found in total outpatient antibiotic use, as well as a significant seasonal variation, which decreased over time from 1997 to 2009. Relative use of penicillins and quinolones significantly increased over time with respect to sulphonamides and trimethoprim, and relative use of quinolones increased with respect to macrolide/lincosamide/streptogramin as well. More detailed analyses of these major antibiotic subgroups will be described in separate papers. CONCLUSIONS: Outpatient antibiotic use in Europe measured as DID has increased since 1997, whereas seasonal variation has decreased over time. European Surveillance of Antimicrobial Consumption (ESAC) data on outpatient antibiotic use in Europe enable countries to audit their antibiotic use. Complemented by longitudinal and compositional data analyses, these data provide a tool for assessing public health strategies aimed at reducing antibiotic resistance and optimizing antibiotic prescribing. PMID- 22096065 TI - European Surveillance of Antimicrobial Consumption (ESAC): outpatient macrolide, lincosamide and streptogramin (MLS) use in Europe (1997-2009). AB - BACKGROUND: Data on more than a decade of outpatient macrolide, lincosamide and streptogramin (MLS) use in Europe were collected from 33 countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC), using the WHO Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) methodology. METHODS: For the period 1997-2009, data on outpatient use of systemic MLS aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2011) per 1000 inhabitants per day (DID). Using a classification based on mean plasma elimination half-life, macrolide use was analysed for trends over time, seasonal variation and composition. RESULTS: Total outpatient MLS use in 2009 varied by a factor of 18 between the countries with highest (11.5 DID in Greece) and lowest (0.6 DID in Sweden) use. MLS use showed high seasonal variation. Short-, intermediate- and long-acting macrolides were the most commonly used agents in 2, 25 and 5 countries, respectively (mainly erythromycin, clarithromycin and azithromycin, respectively). In Sweden, mainly lincosamides (clindamycin) were used. Lincosamide use was observed in all countries, while substantial use of a streptogramin was only seen in France (pristinamycin). For Europe, a significant increase in outpatient MLS use was found, as well as a significant seasonal variation, which increased over time from 1997 to 2009. Relative use of long-acting macrolides and lincosamides significantly increased over time with respect to intermediate-acting macrolides, and relative use of the latter increased with respect to short-acting macrolides. CONCLUSIONS: The observed differences between European countries in the levels of MLS use and the extreme seasonal variations in their use suggest that this subgroup of antibiotics is still prescribed inappropriately in many countries. PMID- 22096066 TI - European Surveillance of Antimicrobial Consumption (ESAC): outpatient quinolone use in Europe (1997-2009). AB - BACKGROUND: Data on more than a decade of outpatient quinolone use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). METHODS: For the period 1997-2009, data on outpatient use of systemic quinolones aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011), and expressed in DDD and packages per 1000 inhabitants per day (DID and PID, respectively). Using a classification based on pharmacokinetic and in vitro potency profiles, quinolone use was analysed with regard to trends over time, seasonal variation and composition. RESULTS: Total outpatient quinolone use in 2009 varied by a factor of 7.5 between the country with the highest (Italy, 3.61 DID) and the country with the lowest (the UK, 0.48 DID) quinolone use. The second-generation quinolones accounted for >50% of quinolone use (mainly ciprofloxacin), except for Croatia, where first-generation quinolones (mainly norfloxacin) were mostly used. A significant increase in outpatient quinolone use was found for Europe, as well as a large seasonal variation, which increased significantly over time from 1997 to 2009. Relative use of third-generation quinolones significantly increased over time with respect to the use of second-generation quinolones, while the relative use of both significantly increased with respect to the first-generation quinolones. Levofloxacin and moxifloxacin (respiratory quinolones) represented >10% of quinolone outpatient use in 17 countries, with extreme seasonal variation in all countries. CONCLUSIONS: There was a substantial increase and change in the pattern of quinolone use between 1997 and 2009, a period during which quinolones that are effective for the treatment of respiratory tract infections were introduced. These quinolones are not the first-line antibiotics for this indication and their use should generally be limited, and quinolones should ideally show no substantial seasonal variation in terms of their use. PMID- 22096069 TI - Application of mixed-effects models to study the country-specific outpatient antibiotic use in Europe: a tutorial on longitudinal data analysis. AB - Resistance to antibiotics is a major public health problem and antibiotic use is being increasingly recognized as the main selective pressure driving this resistance. Yearly and quarterly data on outpatient antibiotic use were collected by the European Surveillance of Antimicrobial Consumption (ESAC) project for the period 1997-2009 from 33 and 27 European countries, respectively, and expressed in defined daily doses per 1000 inhabitants per day. Since repeated measures were taken for the countries, correlation has to be taken into account when analysing the data. This paper illustrates the application of mixed-effects models to the study of country-specific outpatient antibiotic use in Europe. Mixed models are useful in a wide variety of disciplines in the biomedical, physical and social sciences. In this application for outpatient antibiotic use, the linear mixed model is extended to a non-linear mixed model, allowing analysis of seasonal variation on top of a global trend, with country-specific effects for global mean use and amplitude, and trends over time in use and in amplitude. PMID- 22096068 TI - European Surveillance of Antimicrobial Consumption (ESAC): quality appraisal of antibiotic use in Europe. AB - OBJECTIVES: To assess quality of outpatient antibiotic use in Europe in 2009 based on the 12 European Surveillance of Antimicrobial Consumption (ESAC) drug specific quality indicators and to evaluate changes in quality between 2004 and 2009. METHODS: Quality of outpatient antibiotic use in 2009 was compared between 32 countries by calculating the indicator values for 2009 for each of the 12 ESAC drug-specific quality indicators based on outpatient antibiotic use data expressed in defined daily doses per 1000 inhabitants per day (DID). For each of the indicators we grouped the 2009 indicator values into four quartiles. To evaluate changes in quality between 2004 and 2009, based on their respective indicator values, countries were also grouped according to the quartile distribution of the 2004 indicator values. Only countries able to deliver data for both years were included in this analysis. RESULTS: In 2009 a difference in the quality of outpatient antibiotic use between Nordic and Southern European countries was observed. Quality of outpatient antibiotic use decreased between 2004 and 2009. In particular, there were increases in the quality indicators [J01F_DID], [J01M_DID], [J01CR_%] and [J01_B/N], i.e. the use of macrolides, lincosamides and streptogramins in DID, the use of quinolones in DID, the proportional use of combinations of penicillins, including beta-lactamase inhibitors and the ratio of broad- to narrow-spectrum antibiotics. CONCLUSIONS: Quality of outpatient antibiotic use in DID decreased between 2004 and 2009. A continuous effort to improve outpatient antibiotic consumption seems to be essential to reduce outpatient antibiotic use in general and the use of broad spectrum antibiotics in particular. PMID- 22096067 TI - European Surveillance of Antimicrobial Consumption (ESAC): outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in Europe (1997-2009). AB - BACKGROUND: Data on more than a decade of outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in Europe were collected from 33 countries as part of the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). METHODS: For the period 1997-2009, data on outpatient use of systemic tetracyclines, sulphonamides and trimethoprim, and other antibacterials aggregated at the level of the active substance were collected and expressed in defined daily doses (DDD; WHO, version 2011) per 1000 inhabitants per day (DID). Using the Anatomical Therapeutic Chemical (ATC) classification, trends in the use of tetracyclines (J01A), sulphonamides and trimethoprim (J01E) and other antibacterials (J01X) over time, seasonal variation and composition of use were analysed. RESULTS: In 2009, the variations in outpatient use of systemic tetracyclines, sulphonamides and trimethoprim, and other antibacterials between countries, and also in the composition of use over time, were huge. For tetracyclines a significant and for sulphonamides and trimethoprim a non significant decrease in use was observed between 1997 and 2009 in Europe. The seasonal variation in their use significantly decreased over time. For the other antibacterials, no significant changes in the volume of use or its seasonal variation were seen. CONCLUSIONS: As for all other major antibiotic subgroups, a striking variation in use and composition of use between countries in Europe was observed for outpatient use of tetracyclines, sulphonamides and trimethoprim, and other antibacterials. In combination with the decreasing use, especially of recommended substances, this represents an opportunity not only to reduce antibiotic use but also to improve its quality. PMID- 22096070 TI - Analysing the composition of outpatient antibiotic use: a tutorial on compositional data analysis. AB - In this tutorial, statistical methods for studying outpatient use of antibiotics in Europe are described, using data provided by IMS Health. The methods are applied to two related research questions, namely the assessment of changes in the relative volume of use of different antibiotic subclasses over time and changes in the absolute volume of antibiotic use. PMID- 22096071 TI - Basolateral rather than apical primary cilia on neuroepithelial cells committed to delamination. AB - Delamination of neural progenitors from the apical adherens junction belt of the neuroepithelium is a hallmark of cerebral cortex development and evolution. Specific cell biological processes preceding this delamination are largely unknown. Here, we identify a novel, pre-delamination state of neuroepithelial cells in mouse embryonic neocortex. Specifically, in a subpopulation of neuroepithelial cells that, like all others, exhibit apical-basal polarity and apical adherens junctions, the re-establishing of the primary cilium after mitosis occurs at the basolateral rather than the apical plasma membrane. Neuroepithelial cells carrying basolateral primary cilia appear at the onset of cortical neurogenesis, increase in abundance with its progression, selectively express the basal (intermediate) progenitor marker Tbr2, and eventually delaminate from the apical adherens junction belt to become basal progenitors, translocating their nucleus from the ventricular to the subventricular zone. Overexpression of insulinoma-associated 1, a transcription factor known to promote the generation of basal progenitors, increases the proportion of basolateral cilia. Basolateral cilia in cells delaminating from the apical adherens junction belt are preferentially found near spot-like adherens junctions, suggesting that the latter provide positional cues to basolateral ciliogenesis. We conclude that re-establishing a basolateral primary cilium constitutes the first known cell biological feature preceding neural progenitor delamination. PMID- 22096072 TI - Differential plasticity of epiblast and primitive endoderm precursors within the ICM of the early mouse embryo. AB - Cell differentiation during pre-implantation mammalian development involves the formation of two extra-embryonic lineages: trophoblast and primitive endoderm (PrE). A subset of cells within the inner cell mass (ICM) of the blastocyst does not respond to differentiation signals and forms the pluripotent epiblast, which gives rise to all of the tissues in the adult body. How this group of cells is set aside remains unknown. Recent studies documented distinct sequential phases of marker expression during the segregation of epiblast and PrE within the ICM. However, the connection between marker expression and lineage commitment remains unclear. Using a fluorescent reporter for PrE, we investigated the plasticity of epiblast and PrE precursors. Our observations reveal that loss of plasticity does not coincide directly with lineage restriction of epiblast and PrE markers, but rather with exclusion of the pluripotency marker Oct4 from the PrE. We note that individual ICM cells can contribute to all three lineages of the blastocyst until peri-implantation. However, epiblast precursors exhibit less plasticity than precursors of PrE, probably owing to differences in responsiveness to extracellular signalling. We therefore propose that the early embryo environment restricts the fate choice of epiblast but not PrE precursors, thus ensuring the formation and preservation of the pluripotent foetal lineage. PMID- 22096073 TI - Gbetagamma signaling controls the polarization of zebrafish primordial germ cells by regulating Rac activity. AB - During development, primordial germ cells (PGCs) migrate from the sites of their specification towards the region in which the future gonad develops. This cell migration requires polarization of PGCs and their responsiveness to external guidance cues. In zebrafish, the directed migration and polarization of PGCs are regulated independently, by the chemokine Cxcl12a and the Rho GTPase Rac1, respectively. However, the upstream signals controlling Rac activity in this context have not yet been identified. By investigating the role of G proteins in PGC migration, we found that signaling mediated by G protein subunits Gbetagamma is required to regulate cell polarization. PGCs that are defective for Gbetagamma signaling failed to polarize, and developed multiple protrusions in random locations, resembling the defects observed in PGCs with decreased Rac activity. These defects render PGCs incapable of migrating actively and responding to directional cues. FRET-based assays showed that PGCs require Gbetagamma signaling for polarized Rac activation and actin organization at the leading front, as well as for maintaining overall Rac levels in these cells. Conversely, overexpression of Gbetagamma in PGCs increases Rac activity. Our results indicate that during PGC migration in vivo, Gbetagamma signaling regulates Rac activity to control cell polarity, which is required for the responsiveness to chemokine signaling. PMID- 22096074 TI - The role of the histone H2A ubiquitinase Sce in Polycomb repression. AB - Polycomb group (PcG) proteins exist in multiprotein complexes that modify chromatin to repress transcription. Drosophila PcG proteins Sex combs extra (Sce; dRing) and Posterior sex combs (Psc) are core subunits of PRC1-type complexes. The Sce:Psc module acts as an E3 ligase for monoubiquitylation of histone H2A, an activity thought to be crucial for repression by PRC1-type complexes. Here, we created an Sce knockout allele and show that depletion of Sce results in loss of H2A monoubiquitylation in developing Drosophila. Genome-wide profiling identified a set of target genes co-bound by Sce and all other PRC1 subunits. Analyses in mutants lacking individual PRC1 subunits reveals that these target genes comprise two distinct classes. Class I genes are misexpressed in mutants lacking any of the PRC1 subunits. Class II genes are only misexpressed in animals lacking the Psc-Su(z)2 and Polyhomeotic (Ph) subunits but remain stably repressed in the absence of the Sce and Polycomb (Pc) subunits. Repression of class II target genes therefore does not require Sce and H2A monoubiquitylation but might rely on the ability of Psc-Su(z)2 and Ph to inhibit nucleosome remodeling or to compact chromatin. Similarly, Sce does not provide tumor suppressor activity in larval tissues under conditions in which Psc-Su(z)2, Ph and Pc show such activity. Sce and H2A monoubiquitylation are therefore only crucial for repression of a subset of genes and processes regulated by PRC1-type complexes. Sce synergizes with the Polycomb repressive deubiquitinase (PR-DUB) complex to repress transcription at class I genes, suggesting that H2A monoubiquitylation must be appropriately balanced for their transcriptional repression. PMID- 22096075 TI - Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. AB - Neurog3-induced Dll1 expression in pancreatic endocrine progenitors ostensibly activates Hes1 expression via Notch and thereby represses Neurog3 and endocrine differentiation in neighboring cells by lateral inhibition. Here we show in mouse that Dll1 and Hes1 expression deviate during regionalization of early endoderm, and later during early pancreas morphogenesis. At that time, Ptf1a activates Dll1 in multipotent pancreatic progenitor cells (MPCs), and Hes1 expression becomes Dll1 dependent over a brief time window. Moreover, Dll1, Hes1 and Dll1/Hes1 mutant phenotypes diverge during organ regionalization, become congruent at early bud stages, and then diverge again at late bud stages. Persistent pancreatic hypoplasia in Dll1 mutants after eliminating Neurog3 expression and endocrine development, together with reduced proliferation of MPCs in both Dll1 and Hes1 mutants, reveals that the hypoplasia is caused by a growth defect rather than by progenitor depletion. Unexpectedly, we find that Hes1 is required to sustain Ptf1a expression, and in turn Dll1 expression in early MPCs. Our results show that Ptf1a-induced Dll1 expression stimulates MPC proliferation and pancreatic growth by maintaining Hes1 expression and Ptf1a protein levels. PMID- 22096076 TI - Rankl-induced osteoclastogenesis leads to loss of mineralization in a medaka osteoporosis model. AB - Osteoclasts are macrophage-related bone resorbing cells of hematopoietic origin. Factors that regulate osteoclastogenesis are of great interest for investigating the pathology and treatment of bone diseases such as osteoporosis. In mammals, receptor activator of NF-kappaB ligand (Rankl) is a regulator of osteoclast formation and activation: its misexpression causes osteoclast stimulation and osteoporotic bone loss. Here, we report an osteoporotic phenotype that is induced by overexpression of Rankl in the medaka model. We generated transgenic medaka lines that express GFP under control of the cathepsin K promoter in osteoclasts starting at 12 days post-fertilization (dpf), or Rankl together with CFP under control of a bi-directional heat-shock promoter. Using long-term confocal time lapse imaging of double and triple transgenic larvae, we monitored in vivo formation and activation of osteoclasts, as well as their interaction with osteoblasts. Upon Rankl induction, GFP-positive osteoclasts are first observed in the intervertebral regions and then quickly migrate to the surface of mineralized neural and haemal arches, as well as to the centra of the vertebral bodies. These osteoclasts are TRAP (tartrate-resistant acid phosphatase) and cathepsin K positive, mononuclear and highly mobile with dynamically extending protrusions. They are exclusively found in tight contact with mineralized matrix. Rankl induced osteoclast formation resulted in severe degradation of the mineralized matrix in vertebral bodies and arches. In conclusion, our in vivo imaging approach confirms a conserved role of Rankl in osteoclastogenesis in teleost fish and provides new insight into the cellular interactions during bone resorption in an animal model that is useful for genetic and chemical screening. PMID- 22096077 TI - Sox2-mediated differential activation of Six3.2 contributes to forebrain patterning. AB - The vertebrate forebrain is patterned during gastrulation into telencephalic, retinal, hypothalamic and diencephalic primordia. Specification of each of these domains requires the concerted activity of combinations of transcription factors (TFs). Paradoxically, some of these factors are widely expressed in the forebrain, which raises the question of how they can mediate regional differences. To address this issue, we focused on the homeobox TF Six3.2. With genomic and functional approaches we demonstrate that, in medaka fish, Six3.2 regulates, in a concentration-dependent manner, telencephalic and retinal specification under the direct control of Sox2. Six3.2 and Sox2 have antagonistic functions in hypothalamic development. These activities are, in part, executed by Foxg1 and Rx3, which seem to be differentially and directly regulated by Six3.2 and Sox2. Together, these data delineate the mechanisms by which Six3.2 diversifies its activity in the forebrain and highlight a novel function for Sox2 as one of the main regulators of anterior forebrain development. They also demonstrate that graded levels of the same TF, probably operating in partially independent transcriptional networks, pattern the vertebrate forebrain along the anterior-posterior axis. PMID- 22096078 TI - Retinoic acid signaling controls the formation, proliferation and survival of the blastema during adult zebrafish fin regeneration. AB - Adult teleosts rebuild amputated fins through a proliferation-dependent process called epimorphic regeneration, in which a blastema of cycling progenitor cells replaces the lost fin tissue. The genetic networks that control formation of blastema cells from formerly quiescent stump tissue and subsequent blastema function are still poorly understood. Here, we investigated the cellular and molecular consequences of genetically interfering with retinoic acid (RA) signaling for the formation of the zebrafish blastema. We show that RA signaling is upregulated within the first few hours after fin amputation in the stump mesenchyme, where it controls Fgf, Wnt/beta-catenin and Igf signaling. Genetic inhibition of the RA pathway at this stage blocks blastema formation by inhibiting cell cycle entry of stump cells and impairs the formation of the basal epidermal layer, a signaling center in the wound epidermis. In the established blastema, RA signaling remains active to ensure the survival of the highly proliferative blastemal population by controlling expression of the anti apoptotic factor bcl2. In addition, RA signaling maintains blastema proliferation through the activation of growth-stimulatory signals mediated by Fgf and Wnt/beta catenin signaling, as well as by reducing signaling through the growth-inhibitory non-canonical Wnt pathway. The endogenous roles of RA in adult vertebrate appendage regeneration are uncovered here for the first time. They provide a mechanistic framework to understand previous observations in salamanders that link endogenous sources of RA to the regeneration process itself and support the hypothesis that the RA signaling pathway is an essential component of vertebrate tissue regeneration. PMID- 22096079 TI - Drosophila G-protein-coupled receptor kinase 2 regulates cAMP-dependent Hedgehog signaling. AB - G-protein-coupled receptor kinases (GRKs) play a conserved role in Hedgehog (Hh) signaling. In several systems, GRKs are required for efficient Hh target gene expression. Their principal target appears to be Smoothened (Smo), the intracellular signal-generating component of the pathway and a member of the G protein-coupled receptor (GPCR) protein family. In Drosophila, a GRK called Gprk2 is needed for internalization and downregulation of activated Smo, consistent with the typical role of these kinases in negatively regulating GPCRs. However, Hh target gene activation is strongly impaired in gprk2 mutant flies, indicating that Gprk2 must also positively regulate Hh signaling at some level. To investigate its function in signaling, we analyzed several different readouts of Hh pathway activity in animals or cells lacking Gprk2. Surprisingly, although target gene expression was impaired, Smo-dependent activation of downstream components of the signaling pathway was increased in the absence of Gprk2. This suggests that Gprk2 does indeed play a role in terminating Smo signaling. However, loss of Gprk2 resulted in a decrease in cellular cAMP concentrations to a level that was limiting for Hh target gene activation. Normal expression of target genes was restored in gprk2 mutants by stimulating cAMP production or activating the cAMP-dependent Protein kinase A (Pka). Our results suggest that direct regulation of Smo by Gprk2 is not absolutely required for Hh target gene expression. Gprk2 is important for normal cAMP regulation, and thus has an indirect effect on the activity of Pka-regulated components of the Hh pathway, including Smo itself. PMID- 22096081 TI - Effectiveness and acceptability of delivery of antiretroviral treatment in health centres by health officers and nurses in Ethiopia. AB - OBJECTIVE: The World Health Organization (WHO) recommends shifting tasks from physicians to lower cadres for the delivery of antiretroviral treatment (ART) for countries short of physicians. Our objective was to evaluate the effectiveness and acceptability of ART delivery by health officers and nurses in Ethiopia. METHODS: A retrospective cohort study to evaluate outcomes of ART services in 25 health centres staffed with health officers and/or nurses and 30 hospitals staffed with physicians in 2009. Median CD4-cell counts, mortality, loss to follow-up and retention were the primary outcomes. Interviews and focus group discussions were conducted with people living with HIV/AIDS, AIDS programme managers and health care providers to identify the types and acceptability of the tasks conducted by the health officers, nurses and community health workers. RESULTS: Health officers and nurses were providing ART, including ART prescription, for non-severe cases. The management of severe cases was exclusively the task of physicians. Community health workers were involved in adherence counselling and defaulter tracing. The baseline median CD4-cell counts per micro-liter of blood were 117 (interquartiles [IQ] 64,188) and 119 (IQ 67,190) at health centres and hospitals respectively. After 24 months on ART, the median CD4-cell counts per micro-liter of blood increased to 321 (IQ 242, 414) and 301 (IQ 217, 411) at health centres and hospitals respectively. Retention in care was higher in health centres (76%, 95% confidence interval [CI] [73%-79%]) than hospitals (67%, 95% CI [66%-68%]). This difference is mainly due to the higher loss to follow-up rate in hospitals (25% versus 13%). Mortality was higher in health centres than hospitals (11% versus 8%), but the difference is not statistically significant. Service delivery by non-physicians was accepted by patients, health care providers and programme managers. However, the absence of a regulatory framework for task shifting, the lack of extra remuneration for the additional roles assumed by nurses and health officers, and the high cost for training and mentorship were identified as weaknesses. CONCLUSION: ART delivery in health centres, based on health officers and nurses is feasible, effective and acceptable in Ethiopia. However, issues related to regulation, remuneration and cost need to be addressed for the sustainable implementation of these delivery models. PMID- 22096082 TI - Assessing the effects of removing user fees in Zambia and Niger. AB - OBJECTIVES: This study aims to overcome some of the limitations of previous studies investigating the effects of fee removal, by looking at heterogeneity of effects within countries and over time, as well as the existence of spill-over effects on groups not targeted by the policy change. METHODS: Using routine district health services data before and after recent abolitions of user charges in Zambia and Niger, we examine the effects of the policy change on the use of health services by different groups and over time, using an interrupted timeseries design. RESULTS: Removing user fees for primary health care services in rural districts in Zambia and for children over five years old in Niger increased use of services by the targeted groups. The impact of the policy change differed widely across districts, ranging from +12% and +194% in Niger to -39% and +108% in Zambia. Eighteen months after the policy change, some of these effects had been eroded. There was evidence that abolishing user fees can both have positive and negative spillover effects. CONCLUSION: These results highlight the importance of paying attention to implementation challenges and monitoring the effects of policy reforms which are often more mixed and complicated that they appear. The comparison of these reforms in two countries also sheds light on the potentially different ways in which free care can be used as a tool to improve access. PMID- 22096080 TI - Dynamic interactions of high Cdt1 and geminin levels regulate S phase in early Xenopus embryos. AB - Cdt1 plays a key role in licensing DNA for replication. In the somatic cells of metazoans, both Cdt1 and its natural inhibitor geminin show reciprocal fluctuations in their protein levels owing to cell cycle-dependent proteolysis. Here, we show that the protein levels of Cdt1 and geminin are persistently high during the rapid cell cycles of the early Xenopus embryo. Immunoprecipitation of Cdt1 and geminin complexes, together with their cell cycle spatiotemporal dynamics, strongly supports the hypothesis that Cdt1 licensing activity is regulated by periodic interaction with geminin rather than its proteolysis. Overexpression of ectopic geminin slows down, but neither arrests early embryonic cell cycles nor affects endogenous geminin levels; apparent embryonic lethality is observed around 3-4 hours after mid-blastula transition. However, functional knockdown of geminin by DeltaCdt1_193-447, which lacks licensing activity and degradation sequences, causes cell cycle arrest and DNA damage in affected cells. This contributes to subsequent developmental defects in treated embryos. Our results clearly show that rapidly proliferating early Xenopus embryonic cells are able to regulate replication licensing in the persistent presence of high levels of licensing proteins by relying on changing interactions between Cdt1 and geminin during the cell cycle, but not their degradation. PMID- 22096083 TI - Predicting phenolic acid absorption in Caco-2 cells: a theoretical permeability model and mechanistic study. AB - There is a considerable need to rationalize the membrane permeability and mechanism of transport for potential nutraceuticals. The aim of this investigation was to develop a theoretical permeability equation, based on a reported descriptive absorption model, enabling calculation of the transcellular component of absorption across Caco-2 monolayers. Published data for Caco-2 permeability of 30 drugs transported by the transcellular route were correlated with the descriptors 1-octanol/water distribution coefficient (log D, pH 7.4) and size, based on molecular mass. Nonlinear regression analysis was used to derive a set of model parameters a', beta', and b' with an integrated molecular mass function. The new theoretical transcellular permeability (TTP) model obtained a good fit of the published data (R2 = 0.93) and predicted reasonably well (R2 = 0.86) the experimental apparent permeability coefficient (P(app)) for nine non training set compounds reportedly transported by the transcellular route. For the first time, the TTP model was used to predict the absorption characteristics of six phenolic acids, and this original investigation was supported by in vitro Caco-2 cell mechanistic studies, which suggested that deviation of the P(app) value from the predicted transcellular permeability (P(app)(trans)) may be attributed to involvement of active uptake, efflux transporters, or paracellular flux. PMID- 22096084 TI - Assessment of the impact of CYP3A polymorphisms on the formation of alpha hydroxytamoxifen and N-desmethyltamoxifen in human liver microsomes. AB - Tamoxifen, an antiestrogen used in the prevention and treatment of breast cancer, is extensively metabolized by cytochrome P450 enzymes. Its biotransformation to alpha-hydroxytamoxifen (alpha-OHT), which may be genotoxic, and to N desmethyltamoxifen (N-DMT), which is partially hydroxylated to 4-hydroxy-N-DMT (endoxifen), a potent antiestrogen, is mediated by CYP3A enzymes. However, the potential contribution of CYP3A5 and the impact of its low-expression variants on the formation of these metabolites are not clear. Therefore, we assessed the contributions of CYP3A4 and CYP3A5 and examined the impact of CYP3A5 genotypes on the formation of alpha-OHT and N-DMT, by using recombinant CYP3A4 and CYP3A5 and human liver microsomes (HLM) genotyped for CYP3A5 variants. We observed that the catalytic efficiency [intrinsic clearance (CL(int))] for alpha-OHT formation with recombinant CYP3A4 was 5-fold higher than that with recombinant CYP3A5 (0.81 versus 0.16 nl . min-1 . pmol cytochrome P450-1). There was no significant difference in CL(int) values between the three CYP3A5-genotyped HLM (*1/*1, *1/*3, and *3/*3). For N-DMT formation, the CL(int) with recombinant CYP3A4 was only 1.7-fold higher, relative to that with recombinant CYP3A5. In addition, the CL(int) for N-DMT formation by HLM with CYP3A5*3/*3 alleles was approximately 3 fold lower than that for HLM expressing CYP3A5*1/*1. Regression analyses of tamoxifen metabolism with respect to testosterone 6beta-hydroxylation facilitated assessment of CYP3A5 contributions to the formation of the two metabolites. The CYP3A5 contributions to alpha-OHT formation were negligible, whereas the contributions to N-DMT formation ranged from 51 to 61%. Our findings suggest that polymorphic CYP3A5 expression may affect the formation of N-DMT but not that of alpha-OHT. PMID- 22096085 TI - Transurethral seminal vesiculoscopy using a 6F vesiculoscope for ejaculatory duct obstruction: initial experience. AB - Ejaculatory duct obstruction (EDO) is a surgically correctable condition that occurs in some infertile men. The standard therapy is transurethral resection of ejaculatory ducts (TURED). However, TURED has been associated with a high risk of complications, including the impairment of semen parameters and retrograde ejaculation. In our clinical practice, vesiculoscopy has demonstrated potential as a minimally invasive alternative technique for the diagnosis and treatment of EDO. Very few studies have examined transurethral seminal vesiculoscopy (TRU SVS) in recent years, and no study has examined 6F vesiculoscopes. Therefore, we performed a retrospective study of TRU-SVS using a 6F vesiculoscope and its effect on the diagnosis and treatment of EDO. A total of 21 patients who underwent this procedure were included in the study. The mean patient age was 28.8 years (range, 23-36 years). The procedure was completed successfully in all patients within a mean time of 31.5 minutes and a mean hospital stay of 1.17 days. All patients had EDO. Calculi were found in the ejaculatory ducts or in the seminal vesicles of 5 patients. Sperm was detected in 11 patients 1-3 months postsurgery and in another 8 patients 3-12 months postsurgery. No sperm was detected in the remaining 2 patients by 12 months postsurgery. Epididymitis, retrograde ejaculation, urinary incontinence, and rectal injury were not observed. These data indicate that TRU-SVS using a 6F vesiculoscope affords direct access to the seminal vesicle and offers the advantages of fewer complications and more optimal sperm recovery as well as direct, dynamic video imaging. PMID- 22096086 TI - A possible role for perforin and granzyme B in resveratrol-enhanced radiosensitivity of prostate cancer. AB - Perforin and granzyme B are expressed primarily by activated lymphocytes (cytotoxic T cells, natural killer cells, and natural killer T cells) and function together to induce apoptosis of target cells. Typically, these proteins are not expressed in tumor cells. In the present study, we established the constitutive expression of perforin and granzyme B by the PC-3 and DU145 prostate cancer (PCA) cell lines with reverse transcription polymerase chain reaction, immunohistochemistry, Western blot, or a combination of techniques. The combination of radiation and resveratrol (XRT/RSV) additively/synergistically decreased survival of PCA because, at least in part, of increased apoptosis. We further demonstrated that treatment with RSV up regulated the expression of both perforin and granzyme B, whereas treatment with XRT up-regulated the expression of granzyme B, but not that of perforin. Combined XRT/RSV treatment of PCA cells further increased the expression of both perforin and granzyme B compared with RSV or XRT alone. Thus, increased radiosensitivity of prostate cancer cells induced by RSV correlated with up regulation of perforin and granzyme B, demonstrating a possible mechanism for tumor apoptosis. These findings might be helpful in devising new strategies for treating PCA. PMID- 22096087 TI - Penile cavernosal artery pseudoaneurysm. AB - A patient presented with a mass in the cavernous body. The mass, 1 cm in diameter, was detected in the left cavernous body on the MRI and color Doppler ultrasound of the penis of the patient, who presented with pain approximately 3 months after a blunt trauma to the pelvic region. According to the statement of the patient, any direct trauma to the penis was obscure. The lesion was resected and pathological examination of the removed mass revealed pseudoaneurysm. PMID- 22096088 TI - Sertraline and mirtazapine do not reduce severity of depression in people with dementia. PMID- 22096089 TI - No free lunches: balancing bleeding and efficacy with ticagrelor. PMID- 22096090 TI - Temporal trends of the gaps in post-myocardial infarction secondary prevention strategies of co-morbid and elderly populations vs. younger counterparts: an analysis of three successive cohorts between 2003 and 2008. AB - Aims Epidemiological studies reported two contrasting trends: on one hand, a significant improvement in the use of evidence-based treatments of patients discharged with a myocardial infarction (MI). On the other hand, the increasing number of elderly and co-morbid patients who are usually less treated. The aim of this study is to examine whether improvements in the treatment of MI are homogeneously distributed throughout all subgroups of patients. Methods and results Based on record linkage of administrative registers, 21 423 patients discharged with MI in three different periods (2003, 2005, and 2007), were identified and followed up for major clinical events up to 1 year. Using as a reference temporal category those patients discharged in 2003 (odds ratios, 95% confidence intervals) and as a demographic category male patients aged <=75 years (1.00), the study identified: in-hospital mortality significantly decreased in all periods and in all groups of patients; out-of-hospital mortality decreased only in younger patients and not in older patients; prescription of evidence based treatments increased in all periods for all patients; however, the magnitude of improvement was mostly concentrated in younger patients. Conclusion Although there was a mean improvement in the treatment and outcome of patients discharged from an MI, most of these benefits were strongly concentrated in younger, healthier patients. Old and co-morbid populations-although representing a substantial proportion of the burden of disease-received significant less attention and barely improved their survival. PMID- 22096091 TI - 2011 Nobel Prize in Physiology or Medicine: Toll-like receptors, dendritic cells, and their roles in atherosclerosis. PMID- 22096092 TI - The controversial role of the urokinase system in abdominal aortic aneurysm formation and rupture. PMID- 22096093 TI - Smooth muscle cells for vascular engineering. PMID- 22096095 TI - Calcific aortic valve disease: cellular origins of valve calcification. PMID- 22096094 TI - We can do it together: PAR1/PAR2 heterodimer signaling in VSMCs. PMID- 22096096 TI - Cell death in cardiovascular disease. PMID- 22096097 TI - Cell death, damage-associated molecular patterns, and sterile inflammation in cardiovascular disease. AB - Cell death and inflammation are ancient processes of fundamental biological importance in both normal physiology and pathology. This is evidenced by the profound conservation of mediators, with ancestral homologues identified from plants to humans, and the number of diseases driven by aberrant control of either process. Apoptosis is the most well-studied cell death, but many forms exist, including autophagy, necrosis, pyroptosis, paraptosis, and the obscure dark cell death. Cell death occurs throughout the cardiovascular system, from initial shaping of the heart and vasculature during development to involvement in pathologies, including atherosclerosis, aneurysm, cardiomyopathy, restenosis, and vascular graft rejection. However, determining whether cell death primarily drives pathology or is a secondary bystander effect is difficult. Inflammation, the primary response of innate immunity, is considered essential in initiating and driving vascular diseases. Cell death and inflammation are inextricably linked with their effectors modulating the other process. Indeed, an evolutionary link between cell death and inflammation occurs at caspase-1 (which activates interleukin-1beta), which can induce death by pyroptosis, and is a member of the caspase family vital for apoptosis. This review examines cell death in vascular disease, how it can induce inflammation, and finally the emergence of inflammasomes in vascular pathology. PMID- 22096098 TI - Autophagy in atherosclerosis: a potential drug target for plaque stabilization. AB - Evidence is accumulating that autophagy occurs in advanced atherosclerotic plaques. Although there is an almost relentless discovery of molecules that are involved in autophagy, studies of selective autophagy induction or inhibition using knockout mice are just now beginning to reveal its biological significance. Most likely, autophagy safeguards plaque cells against cellular distress, in particular oxidative injury, by degrading the damaged intracellular material. In this way, autophagy is protective and contributes to cellular recovery in an unfavorable environment. Pharmacological approaches have recently been developed to stabilize vulnerable, rupture-prone lesions through induction of autophagy. This approach has proven to be successful in short-term studies. However, how autophagy induction affects processes such as inflammation remains to be elucidated and is currently under investigation. This review highlights the possibilities for exploiting autophagy as a drug target for plaque stabilization. PMID- 22096099 TI - Mechanisms of ER stress-induced apoptosis in atherosclerosis. AB - Endoplasmic reticulum (ER) stress is triggered by perturbations in ER function such as those caused by protein misfolding or by increases in protein secretion. Eukaryotic cells respond to ER stress by activating 3 ER-resident proteins, activating transcription factor-6, inositol requiring protein-1, and protein kinase RNA-like ER kinase (PERK). These proteins direct signaling pathways that relieve ER stress in a process known as the unfolded protein response (UPR). In pathological settings, however, prolonged UPR activation can promote cell death, and this process has recently emerged as an important concept in atherosclerosis. We review here the evidence for UPR activation and cell death in macrophages, smooth muscle cells, and endothelial cells in the context of advanced atherosclerosis as well as the existing literature regarding mechanisms of UPR induced cell death. Knowledge in this area may suggest new therapeutic targets relevant to the formation of clinically dangerous atherosclerotic plaques. PMID- 22096100 TI - Host proteasomal degradation generates amino acids essential for intracellular bacterial growth. AB - Legionella pneumophila proliferates in environmental amoeba and human cells within the Legionella-containing vacuole (LCV). The exported AnkB F-box effector of L. pneumophila is anchored into the LCV membrane by host-mediated farnesylation. Here, we report that host proteasomal degradation of Lys(48) linked polyubiquitinated proteins, assembled on the LCV by AnkB, generates amino acids required for intracellular bacterial proliferation. The severe defect of the ankB null mutant in proliferation within amoeba and human cells is rescued by supplementation of a mixture of amino acids or cysteine, serine, pyruvate, or citrate, similar to rescue by genetic complementation. Defect of the ankB mutant in intrapulmonary proliferation in mice is rescued upon injection of a mixture of amino acids or cysteine. Therefore, Legionella promotes eukaryotic proteasomal degradation to generate amino acids needed as carbon and energy sources for bacterial proliferation within evolutionarily distant hosts. PMID- 22096102 TI - The structure of the eukaryotic ribosome at 3.0 A resolution. AB - Ribosomes translate genetic information encoded by messenger RNA into proteins. Many aspects of translation and its regulation are specific to eukaryotes, whose ribosomes are much larger and intricate than their bacterial counterparts. We report the crystal structure of the 80S ribosome from the yeast Saccharomyces cerevisiae--including nearly all ribosomal RNA bases and protein side chains as well as an additional protein, Stm1--at a resolution of 3.0 angstroms. This atomic model reveals the architecture of eukaryote-specific elements and their interaction with the universally conserved core, and describes all eukaryote specific bridges between the two ribosomal subunits. It forms the structural framework for the design and analysis of experiments that explore the eukaryotic translation apparatus and the evolutionary forces that shaped it. PMID- 22096101 TI - Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery. AB - Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration < 1 micromolar) and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open-source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms. PMID- 22096103 TI - Calibrating the end-Permian mass extinction. AB - The end-Permian mass extinction was the most severe biodiversity crisis in Earth history. To better constrain the timing, and ultimately the causes of this event, we collected a suite of geochronologic, isotopic, and biostratigraphic data on several well-preserved sedimentary sections in South China. High-precision U-Pb dating reveals that the extinction peak occurred just before 252.28 +/- 0.08 million years ago, after a decline of 2 per mil (0/00) in delta(13)C over 90,000 years, and coincided with a delta(13)C excursion of -50/00 that is estimated to have lasted <=20,000 years. The extinction interval was less than 200,000 years and synchronous in marine and terrestrial realms; associated charcoal-rich and soot-bearing layers indicate widespread wildfires on land. A massive release of thermogenic carbon dioxide and/or methane may have caused the catastrophic extinction. PMID- 22096104 TI - The origin of OB runaway stars. AB - About 20% of all massive stars in the Milky Way have unusually high velocities, the origin of which has puzzled astronomers for half a century. We argue that these velocities originate from strong gravitational interactions between single stars and binaries in the centers of star clusters. The ejecting binary forms naturally during the collapse of a young (<=1 million years old) star cluster. This model replicates the key characteristics of OB runaways in our galaxy, and it explains the presence of runaway stars of >=100 solar masses (M(?)) around young star clusters, such as R136 and Westerlund 2. The high proportion and the distributions in mass and velocity of runaways in the Milky Way are reproduced if the majority of massive stars are born in dense and relatively low-mass (5000 to 10,000 M(?)) clusters. PMID- 22096105 TI - Rose and Lalonde in the age of genomics, epigenetics and disparities. PMID- 22096106 TI - Genomics and individuals in public health practice: are we luddites or can we meet the challenge? PMID- 22096107 TI - Public health, genomics and autonomy: comment on Dr R.L. Zimmern's Genomics and individuals in public health practice: are we luddites or can we meet the challenge? PMID- 22096108 TI - Genomics, individuals and public health: a view from clinical genetics: comment on Dr R.L. Zimmern's Genomics and individuals in public health practice: are we luddites or can we meet the challenge? PMID- 22096109 TI - Yes, but ... * comment on Dr R.L. Zimmern's Genomics and individuals in public health practice: are we luddites or can we meet the challenge? PMID- 22096110 TI - Communicating with decision-makers through evidence reviews. PMID- 22096111 TI - Beneficial effect of real-time continuous glucose monitoring system on glycemic control in type 1 diabetic patients: systematic review and meta-analysis of randomized trials. AB - OBJECTIVE: Real-time continuous glucose monitoring (RT-CGM) provides detailed information on glucose patterns and trends, thus allowing the patients to manage their diabetes more effectively. DESIGN: The aim of this study was to explore the potential beneficial effects of the use of RT-CGM on diabetes management compared with self blood glucose measurement (SBGM) in patients with type 1 diabetes mellitus (T1DM), by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched through by two independent investigators for RCTs concerning the use of RT-CGM in patients with T1DM. Only studies with a similar insulin regimen in the experimental and control groups were included in the analysis. RESULTS: Seven RCTs (n=948) met the inclusion criteria. Combined data from all studies showed better HbA1c reduction in subjects using RT-CGM compared with those using SBGM (mean difference (MD) -0.25; 95% confidence interval (95% CI): from -0.34 to 0.17; P<0.001). Patients treated with insulin pump and RT-CGM had a lower HbA1c level compared with subjects managed with insulin pump and SBGM (four RCTs, n=497; MD -0.26; 95% CI: from -0.43 to -0.10; P=0.002). The benefits of applying RT-CGM were not associated with an increasing rate of major hypoglycemic episodes. The use of RT-CGM for over 60-70% of time was associated with a significant lowering of HbA1c. CONCLUSIONS: RT-CGM is more beneficial than SBGM in reducing HbA1c in patients with type 1 diabetes. Further studies are needed to evaluate the efficacy of this system in the pediatric population, especially in very young children. PMID- 22096112 TI - Recent advances in cardiovascular aspects of polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) has been associated with increased cardiovascular risk (CVR) markers, but population studies have not clarified whether there is an increase in cardiovascular morbidity and mortality. Four different PCOS phenotypes resulted from the Rotterdam criteria that may differ in their CVR potential, thus introducing further complexity. This has led to studies using surrogate CVR markers including biomarkers in blood and imaging such as flow-mediated vasodilatation. In PCOS, both peripheral and central insulin resistance (IR) have been shown. Weight loss has been shown to improve IR and visceral fat, while insulin sensitizer therapies with metformin or thiazolidinediones improve IR and endothelial dysfunction. IR is also found in non-alcoholic fatty liver disease that in turn is very common in PCOS; studies have suggested that IR may be improved by treatment with metformin and omega-3 fish oils. PCOS patients have a more dyslipidemic phenotype that is worse in 'classical PCOS' associated with a higher CVR. Studies with atorvastatin and simvastatin have reported a decrease in the lipid parameters and an improvement in CVR indices including IR, but it is unclear whether this is due to their lipid lowering action or a pleiotropic effect of the statin. In this expert opinion review, the relevant literature published during the last 2 years was considered. It focuses on some recent important data that has emerged while also exposing the gaps that remain in our knowledge that need to be addressed. PMID- 22096113 TI - Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement. AB - OBJECTIVE: Many patients treated for craniopharyngioma (CP) complain of a relative incapacity for physical activity. Whether this is due to an objective decrease in adaptation to exercise is unclear. We assessed exercise tolerance in children with surgically treated CP and appropriate pituitary hormone replacement therapy compared with healthy controls and we examined the potential relationships with hypothalamic involvement, GH replacement, and the catecholamine deficiency frequently observed in these subjects. DESIGN AND METHODS: Seventeen subjects (12 males and five females) with CP and 22 healthy controls (14 males and eight females) aged 15.3+/-2.5 years (7.3-18 years) underwent a standardized cycle ergometer test. Maximum aerobic capacity was expressed as the ratio of VO(2max) to fat-free mass (VO(2max)/FFM), a measure independent of age and fat mass in children. RESULTS: VO(2max)/FFM was 20% lower in children with CP compared with controls (P<0.05), even after adjustment for gender. Children with hypothalamic involvement (n=10) had a higher percentage of fat mass (P<0.05) than those without hypothalamic involvement (n=7) and lower VO(2max)/FFM (P<0.05), whereas children without hypothalamic involvement had VO(2max)/FFM close to that of controls (P>0.05). GH treatment was associated with a significant positive effect on aerobic capacity (P<0.05) only in the absence of hypothalamic involvement. No relationship was found between exercise capacity parameters and daily urine epinephrine excretion or epinephrine peak response to insulin-induced hypoglycemia. CONCLUSIONS: Children with CP have a decrease in aerobic capacity mainly related to hypothalamic involvement. The hypothalamic factors altering aerobic capacity remain to be determined. PMID- 22096114 TI - Proteomic analysis of human saliva from lung cancer patients using two dimensional difference gel electrophoresis and mass spectrometry. AB - Lung cancer is often asymptomatic or causes only nonspecific symptoms in its early stages. Early detection represents one of the most promising approaches to reduce the growing lung cancer burden. Human saliva is an attractive diagnostic fluid because its collection is less invasive than that of tissue or blood. Profiling of proteins in saliva over the course of disease progression could reveal potential biomarkers indicative of oral or systematic diseases, which may be used extensively in future medical diagnostics. There were 72 subjects enrolled in this study for saliva sample collection according to the approved protocol. Two-dimensional difference gel electrophoresis combined with MS was the platform for salivary proteome separation, quantification, and identification from two pooled samples. Candidate proteomic biomarkers were verified and prevalidated by using immunoassay methods. There were 16 candidate protein biomarkers discovered by two-dimensional difference gel electrophoresis and MS. Three proteins were further verified in the discovery sample set, prevalidation sample set, and lung cancer cell lines. The discriminatory power of these candidate biomarkers in lung cancer patients and healthy control subjects can reach 88.5% sensitivity and 92.3% specificity with AUC = 0.90. This preliminary data report demonstrates that proteomic biomarkers are present in human saliva when people develop lung cancer. The discriminatory power of these candidate biomarkers indicate that a simple saliva test might be established for lung cancer clinical screening and detection. PMID- 22096115 TI - Morphometric changes in the human pulmonary acinus during inflation. AB - Despite decades of research into the mechanisms of lung inflation and deflation, there is little consensus about whether lung inflation occurs due to the recruitment of new alveoli or by changes in the size and/or shape of alveoli and alveolar ducts. In this study we use in vivo (3)He lung morphometry via MRI to measure the average alveolar depth and alveolar duct radius at three levels of inspiration in five healthy human subjects and calculate the average alveolar volume, surface area, and the total number of alveoli at each level of inflation. Our results indicate that during a 143 +/- 18% increase in lung gas volume, the average alveolar depth decreases 21 +/-5%, the average alveolar duct radius increases 7 +/- 3%, and the total number of alveoli increases by 96 +/- 9% (results are means +/- SD between subjects; P < 0.001, P < 0.01, and P < 0.00001, respectively, via paired t-tests). Thus our results indicate that in healthy human subjects the lung inflates primarily by alveolar recruitment and, to a lesser extent, by anisotropic expansion of alveolar ducts. PMID- 22096116 TI - Mechanisms of systemic vasodilation by lysozyme-c in septic shock. AB - In septic shock (SS), cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme-c (Lzm-S), released from leukocytes, contributed to systemic vasodilation in a canine model of SS. We then delineated the pathway by which this occurs in a canine carotid artery organ bath preparation (CAP). We showed that Lzm-S could intrinsically generate hydrogen peroxide (H(2)O(2)) and that H(2)O(2) subsequently reacted with endogenous catalase to form compound I, an oxidized form of catalase. In turn, compound I led to an increase in cyclic guanosine 3',5'-monophosphate to produce vasodilation. However, it was not clear from previous studies whether it is necessary for Lzm-S to bind to the vasculature to cause vasodilation or, alternatively, whether the generation of H(2)O(2) by Lzm-S in the surrounding medium is all that is required. We examined this question in the present study in which we used multiple preparations. In a partitioned CAP, we found that when we added Lzm-S to a partitioned space in which a semipermeable membrane prevented diffusion of Lzm-S to the carotid artery tissue, vasodilation still occurred because of diffusion of H(2)O(2). On the other hand, we found that Lzm-S could accumulate within the vascular smooth muscle layer (VSML) after 7 h of SS in a canine model. We also determined that when Lzm-S was located in close proximity to vascular smooth muscle cells, it could generate H(2)O(2) to produce lengthening in a human cell culture preparation. We conclude that there are two mechanisms by which Lzm-S can cause vasodilation in SS. In one instance, H(2)O(2) generated by Lzm-S in plasma diffuses to the VSML to cause vasodilation. In a second mechanism, Lzm-S directly binds to the VSML, where it generates H(2)O(2) to produce vasodilation. PMID- 22096117 TI - Compensatory responses to upper airway obstruction in obese apneic men and women. AB - Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age (n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow (P = 0.003) and inspiratory duty cycle (P = 0.017) in response to prolonged periods of UAO and an ~20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) (P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep. PMID- 22096118 TI - Middle cerebral artery alterations in a rat chronic hypoperfusion model. AB - Chronic cerebral hypoperfusion (CHP) induces microvascular changes that could contribute to the progression of vascular cognitive impairment and dementia in the aging brain. This study aimed to analyze the effects of CHP on structural, mechanical, and myogenic properties of the middle cerebral artery (MCA) after bilateral common carotid artery occlusion (BCCAO) in adult male Wistar rats. Sham animals underwent a similar surgical procedure without carotid artery (CA) ligation. After 15 days of occlusion, MCA and CA were dissected and MCA structural, mechanical, and myogenic properties were assessed by pressure myography. Collagen I/III expression was determined by immunofluorescence in MCA and CA and by Western blot in CA. mRNA levels for 1A1, 1A2, and 3A1 collagen subunits were quantified by quantitative real-time PCR in CA. Matrix metalloproteinase (MMP-1, MMP-2, MMP-9, and MMP-13) and hypoxia-inducible factor 1alpha (HIF-1alpha) protein expression were determined in CA by Western blot. BCCAO diminished cross-sectional area, wall thickness, and wall-to-lumen ratio. Nevertheless, whereas wall stress was increased, stiffness was not modified and myogenic response was diminished. Hypoperfusion triggered HIF-1alpha expression. Collagen I/III protein expression diminished in MCA and CA after BCCAO, despite increased mRNA levels for 1A1 and 3A1 collagen subunits. Therefore, the reduced collagen expression might be due to proteolytic degradation, since the expression of MMP-1 and MMP-9 increased in the CA. These data suggest that BCCAO induces hypotrophic remodeling by a mechanism that involves a reduction of collagen I/III in association with increased MMP-1 and MMP-9 and that decreases myogenic tone in major arteries supplying the brain. PMID- 22096120 TI - Spaceflight regulates ryanodine receptor subtype 1 in portal vein myocytes in the opposite way of hypertension. AB - Gravity has a structural role for living systems. Tissue development, architecture, and organization are modified when the gravity vector is changed. In particular, microgravity induces a redistribution of blood volume and thus pressure in the astronaut body, abolishing an upright blood pressure gradient, inducing orthostatic hypotension. The present study was designed to investigate whether isolated vascular smooth muscle cells are directly sensitive to altered gravitational forces and, second, whether sustained blood pressure changes act on the same molecular target. Exposure to microgravity during 8 days in the International Space Station induced the decrease of ryanodine receptor subtype 1 expression in primary cultured myocytes from rat hepatic portal vein. Identical results were found in portal vein from mice exposed to microgravity during an 8 day shuttle spaceflight. To evaluate the functional consequences of this physiological adaptation, we have compared evoked calcium signals obtained in myocytes from hindlimb unloaded rats, in which the shift of blood pressure mimics the one produced by the microgravity, with those obtained in myocytes from rats injected with antisense oligonucleotide directed against ryanodine receptor subtype 1. In both conditions, calcium signals implicating calcium-induced calcium release were significantly decreased. In contrast, in spontaneous hypertensive rat, an increase in ryanodine receptor subtype 1 expression was observed as well as the calcium-induced calcium release mechanism. Taken together, our results shown that myocytes were directly sensitive to gravity level and that they adapt their calcium signaling pathways to pressure by the regulation of the ryanodine receptor subtype 1 expression. PMID- 22096119 TI - Effects of whole body vibration on motor unit recruitment and threshold. AB - Whole body vibration (WBV) has been suggested to elicit reflex muscle contractions but this has never been verified. We recorded from 32 single motor units (MU) in the vastus lateralis of 7 healthy subjects (34 +/- 15.4 yr) during five 1-min bouts of WBV (30 Hz, 3 mm peak to peak), and the vibration waveform was also recorded. Recruitment thresholds were recorded from 38 MUs before and after WBV. The phase angle distribution of all MUs during WBV was nonuniform (P < 0.001) and displayed a prominent peak phase angle of firing. There was a strong linear relationship (r = -0.68, P < 0.001) between the change in recruitment threshold after WBV and average recruitment threshold; the lowest threshold MUs increased recruitment threshold (P = 0.008) while reductions were observed in the higher threshold units (P = 0.031). We investigated one possible cause of changed thresholds. Presynaptic inhibition in the soleus was measured in 8 healthy subjects (29 +/- 4.6 yr). A total of 30 H-reflexes (stimulation intensity 30% Mmax) were recorded before and after WBV: 15 conditioned by prior stimulation (60 ms) of the antagonist and 15 unconditioned. There were no significant changes in the relationship between the conditioned and unconditioned responses. The consistent phase angle at which each MU fired during WBV indicates the presence of reflex muscle activity similar to the tonic vibration reflex. The varying response in high- and low-threshold MUs may be due to the different contributions of the mono- and polysynaptic pathways but not presynaptic inhibition. PMID- 22096121 TI - Mechanism of loss of consciousness during vascular neck restraint. AB - Vascular neck restraint (VNR) is a technique that police officers may employ to control combative individuals. As the mechanism of unconsciousness is not completely understood, we tested the hypothesis that VNR simply compresses the carotid arteries, thereby decreasing middle cerebral artery blood flow. Twenty four healthy police officers (age 35 +/- 4 yr) were studied. Heart rate (HR), arterial pressure, rate of change of pressure (dP/dt), and stroke volume (SV) were measured using infrared finger photoplethysmography. Bilateral mean middle cerebral artery flow velocity (MCAVmean) was measured by using transcranial Doppler ultrasound. Neck pressure was measured using flat, fluid-filled balloon transducers positioned over both carotid bifurcations. To detect ocular fixation, subjects were asked to focus on a pen that was moved from side to side. VNR was released 1-2 s after ocular fixation. Ocular fixation occurred in 16 subjects [time 9.5 +/- 0.4 (SE) s]. Pressures over the right (R) and left (L) carotid arteries were 257 +/- 22 and 146 +/- 18 mmHg, respectively. VNR decreased MCAVmean (R 45 +/- 3 to 8 +/- 4 cm/s; L 53 +/- 2 to 10 +/- 3 cm/s) and SV (92 +/- 4 to 75 +/- 4 ml; P < 0.001). Mean arterial pressure (MAP), dP/dt, and HR did not change significantly. We conclude that the most important mechanism in loss of consciousness was decreased cerebral blood flow caused by carotid artery compression. The small decrease in CO (9.6 to 7.5 l/min) observed would not seem to be important as there was no change in MAP. In addition, with no significant change in HR, ventricular contractility, or MAP, the carotid sinus baroreceptor reflex appears to contribute little to the response to VNR. PMID- 22096122 TI - Epigenetic regulation of the ACE gene might be more relevant to endurance physiology than the I/D polymorphism. PMID- 22096123 TI - Does SIRT1 determine exercise-induced skeletal muscle mitochondrial biogenesis: differences between in vitro and in vivo experiments? PMID- 22096124 TI - Mental health law in motion--confronting new challenges in the modern psychiatric landscape. PMID- 22096125 TI - Mental health law and the EU: the next new regulatory frontier? AB - Over the last decade the EU's engagement with health law and policy has rapidly increased and there is now a growing body of literature highlighting this evolution and the impact of legal and regulatory structures in this area. In contrast the specific impact of EU law and policy in relation to the area of mental health remains the subject of comparatively little engagement. The aim of this paper is to examine whether mental health law and policy will become a major site for EU policy and law in the future. It examines the development of EU policy in this area. It sets this in the context of related legal developments such as the Charter of Fundamental Rights and the new EU Patients Rights Directives. It suggests that while it might be at present premature to envisage that a single body of EU mental health law itself may be unlikely that nonetheless the EU presents what is a potentially very influential site for regulation, law and policy in this area in the years to come. PMID- 22096126 TI - Incapacitated persons and deprivation of liberty: Surrey County Council v CA, LA and MIG and MEG [2010] EWHC 785 (Fam), (Court of Protection) P (otherwise known as MIG) and Q (otherwise known as MEG) v Surrey County Council, CA and LA [2011] EWCA Civ 190. PMID- 22096127 TI - India and euthanasia: the poignant case of Aruna Shanbaug. PMID- 22096128 TI - Only skin deep? The harm of being born a different colour to one's parents: A (a minor) and B (a minor) by C (their mother and next friend) v A Health and Social Services Trust [2010] NIQB 108; [2011] NICA 28. PMID- 22096130 TI - Identification of Trueperella (Arcanobacterium) bernardiae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis and by species-specific PCR. PMID- 22096132 TI - Erysipelothrix rhusiopathiae pneumonia in an immunocompetent patient. AB - Erysipelothrix rhusiopathiae is a Gram-positive bacillus that causes infections primarily in animals. In humans, this bacterium usually causes localized cutaneous infections called erysipeloid. Here we report a case of pneumonia with isolation of E. rhusiopathiae from bronchoalveolar lavage and sputum. To our knowledge, this is the first report of a pneumonia case caused by E. rhusiopathiae confirmed by culture. PMID- 22096131 TI - Antifungal susceptibility profiles of Candida isolates from a prospective survey of invasive fungal infections in Italian intensive care units. AB - The antifungal susceptibility pattern of 302 Candida isolates collected during an Italian survey on invasive fungal infections in an intensive care setting was investigated. The results were correlated with some epidemiological data and compared with the antifungal profiles obtained in a previous survey. No resistance to echinocandins was detected. The overall resistance levels to fluconazole, posaconazole and voriconazole were 12.6, 6.0 and 7.1 %, respectively. Candida tropicalis and Candida parapsilosis accounted for more than half of all the fluconazole resistant isolates. Reduced susceptibility to fluconazole is not uncommon among isolates (12.3 %) and appears to be increasing, particularly among C. parapsilosis isolates, which showed an increase in resistant isolates from 2 % in the 1990s to 25.8 % in the present study. Routine antifungal susceptibility testing of this species is therefore recommended. PMID- 22096133 TI - Detection of the Smqnr quinolone protection gene and its prevalence in clinical isolates of Stenotrophomonas maltophilia in China. AB - The aim of this study was to detect novel variants of the Stenotrophomonas maltophilia Smqnr gene family and analyse the prevalence of Smqnr genes in clinical isolates of S. maltophilia in China. In total, 442 clinical isolates of S. maltophilia were collected from nine hospitals in four provinces in China. Antimicrobial susceptibility testing against six commonly used antibiotics was performed on these isolates. The sequences of the Smqnr genes amplified by PCR were aligned with those of known Smqnr genes in GenBank and an Smqnr database. The resistance rate against co-trimoxazole was highest at 48.6 %, followed by resistance rates against ceftazidime, chloramphenicol, ticarcillin/clavulanate and tigecycline at 28.7, 21.3, 19.0 and 16.1 %, respectively. The highest susceptibility was shown to levofloxacin, with a resistance rate of just 6.1 %. Smqnr genes were detected in 114 isolates, and comprised 11 previously identified genes and 20 new variants, bringing the total number of known Smqnr genes to 47. The 20 novel Smqnr genes were designated Smqnr28-47 and the encoded proteins showed only 1-12 amino acid differences among each other. The most common Smqnr genes in China were Smqnr8 and its variant Smqnr35 with prevalences of 17.5 % (20/114) and 13.2 % (15/114), respectively. Both the known and the novel Smqnr genes were discovered in both quinolone non-sensitive and sensitive isolates with similar frequency, suggesting that the Smqnr gene makes little contribution to quinolone resistance in this organism. PMID- 22096134 TI - False-positive PCR results linked to administration of seasonal influenza vaccine. AB - False-positive PCR results usually occur as a consequence of specimen-to-specimen or amplicon-to-specimen contamination within the laboratory. Evidence of contamination at time of specimen collection linked to influenza vaccine administration in the same location as influenza sampling is described. Clinical, circumstantial and laboratory evidence was gathered for each of five cases of influenza-like illness (ILI) with unusual patterns of PCR reactivity for seasonal H1N1, H3N2, H1N1 (2009) and influenza B viruses. Two 2010 trivalent influenza vaccines and environmental swabs of a hospital influenza vaccination room were also tested for influenza RNA. Sequencing of influenza A matrix (M) gene amplicons from the five cases and vaccines was undertaken. Four 2009 general practitioner (GP) specimens were seasonal H1N1, H3N2 and influenza B PCR positive. One 2010 GP specimen was H1N1 (2009), H3N2 and influenza B positive. PCR of 2010 trivalent vaccines showed high loads of detectable influenza A and B RNA. Sequencing of the five specimens and vaccines showed greatest homology with the M gene sequence of Influenza A/Puerto Rico/8/1934 H1N1 virus (used in generation of influenza vaccine strains). Environmental swabs had detectable influenza A and B RNA. RNA detection studies demonstrated vaccine RNA still detectable for at least 66 days. Administration of influenza vaccines and clinical sampling in the same room resulted in the contamination with vaccine strains of surveillance swabs collected from patients with ILI. Vaccine contamination should therefore be considered, particularly where multiple influenza virus RNA PCR positive signals (e.g. H1N1, H3N2 and influenza B) are detected in the same specimen. PMID- 22096135 TI - Cholangitis with septic shock caused by Raoultella planticola. AB - Raoultella planticola (formerly Klebsiella planticola) is a Gram-negative bacterium that has been rarely reported in association with human infection. Here we describe a case of cholangitis complicated with septic shock caused by R. planticola in an immunocompromised patient with advanced cancer who underwent endoscopic retrograde cholangiopancreatography to extract common bile duct stones. The infection was cleared by piperacillin-tazobactam treatment. PMID- 22096136 TI - Identification of transferable DHA-1 type AmpC beta-lactamases and two mutations in quinolone resistance-determining regions of Salmonella enterica serovar Thompson. PMID- 22096137 TI - Comparison between graded unilateral and bilateral medial rectus recession for esotropia. AB - AIMS: To compare the postoperative surgical outcomes and the changes in deviation achieved per millimetre of recession in patients treated by graded unilateral medial rectus (UMR) or bilateral medial rectus (BMR) recession for small to large angle esotropia with a minimum follow-up of 6 months. METHODS: In a retrospective, consecutive and interventional case series, 102 patients underwent UMR recession and BMR recession for constant esotropia measuring 15-35 prism diopters (PD) and 30-70 PD, respectively, from 1 January 2007 to 30 September 2010. Successful alignment was defined as +/- 8 PD of orthophoria in primary and lateral gaze. RESULTS: No significant difference was observed between: (1) the success rates of the BMR and UMR recession groups at postoperative days 1~3 (p=1.00) or at final follow-up (p=0.421); (2) the variation in the mean change in deviation from postoperative days 1~3 to the final follow-up of the UMR (p=0.58) and BMR (p=0.56) recession groups; and (3) the mean correction in PD per millimetre of muscle recession in the UMR and BMR (p=0.63) recession groups. CONCLUSION: Graded UMR recession for 15-35 PD of esodeviation was as effective as graded BMR recession for 30-70 PD of esodeviation. There was no statistical difference in changes in deviation per millimetre of recession between equivalent amounts of unilateral and bilateral recession. PMID- 22096138 TI - Prevalence of blindness in Western Australia: a population study using capture and recapture techniques. AB - AIM: To determine the prevalence of blinding eye disease in Western Australia using a capture and recapture methodology. METHODS: Three independent lists of residents of Western Australia who were also legally blind were collated during the capture periods in 2008-9. The first list was obtained from the state-wide blind register. A second list comprised patients routinely attending hospital outpatient eye clinics over a 6-month period in 2008. The third list was patients attending ophthalmologists' routine clinical appointments over a 6-week period in 2009. Lists were compared to identify those individuals who were captured on each list and those who were recaptured by subsequent lists. Log-linear models were used to calculate the best fit and estimate the prevalence of blindness in the Western Australian population and extrapolated to a national prevalence of blindness in Australia. RESULTS: 1771 legally blind people were identified on three separate lists. The best estimate of the prevalence of blindness in Western Australia was 3384 (95% CI 2947 to 3983) or 0.15% of the population of 2.25 million. Extrapolating to the national population (21.87 million) gave a prevalence of legal blindness of approximately 32,892 or 0.15%. CONCLUSION: Capture-recapture techniques can be used to determine the prevalence of blindness in whole populations. The calculated prevalence of blindness suggested that up to 30% of legally blind people may not be receiving available financial support and up to 60% were not accessing rehabilitation services. PMID- 22096139 TI - Inhibitory effect of corneal endothelial cells on IL-17-producing Th17 cells. AB - AIM: To determine whether cultured corneal endothelial (CE) cells suppress interleukin 17 (IL-17)-producing effector T cells in vitro. METHODS: CE cell lines established from a normal mouse were used. Target bystander T cells were established from normal splenic T cells with anti-CD3 antibodies. Production of IL-17 by target T cells was evaluated by ELISA, flow cytometry and quantitative PCR. To abolish the CE-inhibitory function, transforming growth factor beta (TGFbeta)-small interfering RNA-transfected CE cells or transwell membrane inserts, which block cell-to-cell contact, were used. RESULTS: Cultured CE cells greatly suppressed the activation of bystander target cells (pan-T, CD4 T, CD8 T, and B cells) in vitro, particularly inflammatory cytokine production by CD4 cells. Cultured CE cells significantly suppressed IL-17-producing T cells and fully suppressed polarised T helper 17 (Th17) cell lines that are induced by Th17 associated differentiation factors. However, CE cells failed to suppress Th17 cells if the CE cell lines were pretreated with TGFbeta small interfering RNA or if direct contact with T cells was blocked with transwell membrane inserts. CONCLUSION: CE cells impair the effector functions and activation of IL-17 producing helper T cells in a cell-contact-dependent mechanism. Thus, corneal endothelium may contribute to the maintenance of the privileged immune status in the eye by inducing peripheral immune tolerance. PMID- 22096140 TI - Self-induced facial excoriations and ocular trauma: a treatment dilemma. PMID- 22096141 TI - Prediction error and myopic shift after intraocular lens implantation (IOL) in paediatric cataract patients. PMID- 22096142 TI - 'Kite-tail' fascia lata strips technique: frontalis suspension using a non endoscopic minimally invasive single-thigh incision approach. AB - AIM: To introduce 'kite-tail' strips or a 'multiple Z-plasty' technique on an autogenous fascia lata graft without a stripper to correct severe blepharoptosis by frontalis suspension and to evaluate its effectiveness on surgical outcome. METHODS: 26 eyelids of 18 patients (seven women, 11 men; 10 unilateral, eight bilateral) underwent this procedure. Only a small skin incision was made on the leg measuring 2 cm. A final of 3.5 * 0.6 cm or 5 * 1 cm fascia lata strip was obtained according to the ptosis laterality. The obtained fascia lata graft was then dissected by a described stripping technique for a final of one or two fascia lata strips approximately 12.5 cm * 2 mm long. Functional and cosmetic results were evaluated and the advantages of this technique were stressed. RESULTS: Mean age was 26.0 years (range 3-64) with a mean follow-up period of 28.8 months (range 6-52). All cases achieved good to excellent final lid positions and adequate cosmetic results with no postoperative early (haemorrhage, wound infection) or late (contour abnormality, overcorrection, muscle herniation, recurrence) complications. CONCLUSIONS: This is an easily mastered, simple, safe and efficient alternative technique that offers various benefits over conventional approaches. It avoids extended blunt dissections and has fewer postoperative leg complaints with less haemorrhage-haematoma formation or muscle prolapsus. It is useful at any age, especially in small children who already have a limited amount of delicate fascia lata and may be preferred when a fasciotome or videoendoscope is not available or fails to harvest sufficient material of fascia lata. PMID- 22096143 TI - A hybrid form of retinopathy of prematurity. AB - AIMS: To study a hybrid pattern of retinopathy of prematurity (ROP) demonstrating both ridge tissue (simulating staged ROP) and flat neovascularisation (simulating aggressive posterior retinopathy of prematurity (APROP)) in the same eye. METHODS: Retrospective chart review from January 2006 to June 2010. We reviewed the retinal drawings and Retcam images for a hybrid pattern of ROP, that is, presence of ridge tissue (characteristic of staged ROP) along with flat neovascular syncytium (characteristic of APROP) in the same eye. RESULTS: 28 eyes of 18 infants had hybrid characteristics. All eyes had severe plus disease, flat new vessels at the junction of the vascular and avascular retina and ridge tissue at variable locations. Three patterns were noted: I Ridge at the junction of vascular and avascular retina (14 (50%) eyes); II Ridge in the vascularised posterior retina (10 (35.71%) eyes); III Ill-defined ridge close to the optic disc, with mat-like fibrous proliferation into the vitreous (4 (14.29%) eyes). After confluent laser photocoagulation, we observed favourable outcome in 92.3% eyes with pattern I, 100% eyes with pattern II and 25% eyes with pattern III disease. CONCLUSION: Some eyes with ROP may have abnormal neovascularisation resembling both APROP and classical staged ROP. It is difficult to characterise these eyes according to the international classification of ROP. However, the presence of plus disease should serve as guide to treatment. PMID- 22096145 TI - Toxoplasma gondii in the peripheral blood of patients with ocular toxoplasmosis. PMID- 22096144 TI - Long-term surgical outcomes of porous polyethylene orbital implants: a review of 314 cases. AB - PURPOSE: This study reports on the long-term surgical outcomes after the insertion of porous Medpor orbital implants into anophthalmic sockets. METHODS: A retrospective chart review of 314 eyes from 314 patients who underwent evisceration, enucleation and secondary procedures using Medpor orbital implants was completed focusing on implant-associated complications and their corrective methods as surgical outcomes. RESULTS: The mean follow-up was 50 months (range 6 107 months). The most common complication was blepharoptosis (n=33, 10.5%). Other postoperative complications were exposure (n=14, 4.5%) and implant infection (n=3, 1%). The complications were successfully managed by surgical repair and/or conservative care. CONCLUSION: Using Medpor resulted in similar surgical outcomes, in terms of the types and frequencies of complications, as other kinds of porous orbital implants. PMID- 22096146 TI - Phylogenomic analysis of polyketide synthase-encoding genes in Trichoderma. AB - Members of the economically important ascomycete genus Trichoderma are ubiquitously distributed around the world. The mycoparasitic lifestyle and plant defence-inducing interactions of Trichoderma spp. make them ideal biocontrol agents. Of the Trichoderma enzymes that produce secondary metabolites, some of which likely play important roles in biocontrol processes, polyketide synthase (PKSs) have garnered less attention than non-ribosomal peptide synthetases such as those that produce peptaibols. We have taken a phylogenomic approach to study the PKS repertoire encoded in the genomes of Trichoderma reesei, Trichoderma atroviride and Trichoderma virens. Our analysis lays a foundation for future research related to PKSs within the genus Trichoderma and in other filamentous fungi. PMID- 22096147 TI - Construction of a chassis for hydrogen production: physiological and molecular characterization of a Synechocystis sp. PCC 6803 mutant lacking a functional bidirectional hydrogenase. AB - Cyanobacteria are photosynthetic prokaryotes that are promising 'low-cost' microbial cell factories due to their simple nutritional requirements and metabolic plasticity, and the availability of tools for their genetic manipulation. The unicellular non-nitrogen-fixing Synechocystis sp. PCC 6803 is the best studied cyanobacterial strain and its genome was the first to be sequenced. The vast amount of physiological and molecular data available, together with a relatively small genome, makes Synechocystis suitable for computational metabolic modelling and to be used as a photoautotrophic chassis in synthetic biology applications. To prepare it for the introduction of a synthetic hydrogen producing device, a Synechocystis sp. PCC 6803 deletion mutant lacking an active bidirectional hydrogenase (DeltahoxYH) was produced and characterized at different levels: physiological, proteomic and transcriptional. The results showed that, under conditions favouring hydrogenase activity, 17 of the 210 identified proteins had significant differential fold changes in comparisons of the mutant with the wild-type. Most of these proteins are related to the redox and energy state of the cell. Transcriptional studies revealed that only six genes encoding those proteins exhibited significant differences in transcript levels. Moreover, the mutant exhibits similar growth behaviour compared with the wild-type, reflecting Synechocystis plasticity and metabolic adaptability. Overall, this study reveals that the Synechocystis DeltahoxYH mutant is robust and can be used as a photoautotrophic chassis for the integration of synthetic constructs, i.e. molecular constructs assembled from well characterized biological and/or synthetic parts (e.g. promoters, regulators, coding regions, terminators) designed for a specific purpose. PMID- 22096148 TI - Modulation of volatile organic compound formation in the Mycodiesel-producing endophyte Hypoxylon sp. CI-4. AB - An endophytic Hypoxylon sp. (strain CI-4) producing a wide spectrum of volatile organic compounds (VOCs), including 1,8-cineole, 1-methyl-1,4-cyclohexadiene and cyclohexane, 1,2,4-tris(methylene), was selected as a candidate for the modulation of VOC production. This was done in order to learn if the production of these and other VOCs can be affected by using agents that may modulate the epigenetics of the fungus. Many of the VOCs made by this organism are of interest because of their high energy densities and thus the potential they might have as Mycodiesel fuels. Strain CI-4 was exposed to the epigenetic modulators suberoylanilide hydroxamic acid (SAHA, a histone deacetylase) and 5-azacytidine (AZA, a DNA methyltransferase inhibitor). After these treatments the organism displayed striking cultural changes, including variations in pigmentation, growth rates and odour, in addition to significant differences in the bioactivities of the VOCs. The resulting variants were designated CI4-B, CI4-AZA and CI4-SAHA. GC/MS analyses of the VOCs produced by the variants showed considerable variation, with the emergence of several compounds not previously observed in the wild-type, particularly an array of tentatively identified terpenes such as alpha thujene, sabinene, gamma-terpinene, alpha-terpinolene and beta-selinene, in addition to several primary and secondary alkanes, alkenes, organic acids and derivatives of benzene. Proton transfer reaction mass spectroscopic analyses showed a marked increase in the ratio of ethanol (mass 47) to the total mass of all other ionizable VOCs, from ~0.6 in the untreated strain CI-4 to ~0.8 in CI-4 grown in the presence of AZA. Strain CI4-B was created by exposure of the fungus to 100 uM SAHA; upon removal of the epigenetic modulator from the culture medium, it did not revert to the wild-type phenotype. Results of this study have implications for understanding why there may be a wide range of VOCs found in various isolates of this fungus in nature. PMID- 22096150 TI - Cumulative effect of prophage burden on Shiga toxin production in Escherichia coli. AB - Shigatoxigenic Escherichia coli (STEC) such as E. coli O157 are significant human pathogens, capable of producing severe, systemic disease outcomes. The more serious symptoms associated with STEC infection are primarily the result of Shiga toxin (Stx) production, directed by converting Stx bacteriophages. During phage mediated replication and host cell lysis, the toxins are released en masse from the bacterial cells, and the severity of disease is linked inexorably to toxin load. It is common for a single bacterial host to harbour more than one heterogeneous Stx prophage, and it has also been recently proven that multiple isogenic prophage copies can exist in a single cell, contrary to the lambda immunity model. It is possible that in these multiple lysogens there is an increased potential for production of Stx. This study investigated the expression profiles of single and double isogenic lysogens of Stx phage 24(B) using quantitative PCR to examine transcription levels, and a reporter gene construct as a proxy for the translation levels of stx transcripts. Toxin gene expression in double lysogens was in excess of the single lysogen counterpart, both in the prophage state and after induction of the lytic life cycle. In addition, double lysogens were found to be more sensitive to an increased induction stimulus than single lysogens, suggesting that maintenance of a stable prophage is less likely when multiple phage genome copies are present. Overall, these data demonstrate that the phenomenon of multiple lysogeny in STEC has the potential to impact upon disease pathology through increased toxin load. PMID- 22096149 TI - Low-carbon acclimation in carboxysome-less and photorespiratory mutants of the cyanobacterium Synechocystis sp. strain PCC 6803. AB - Using metabolic and transcriptomic phenotyping, we studied acclimation of cyanobacteria to low inorganic carbon (LC) conditions and the requirements for coordinated alteration of metabolism and gene expression. To analyse possible metabolic signals for LC sensing and compensating reactions, the carboxysome-less mutant DeltaccmM and the photorespiratory mutant DeltaglcD1/D2 were compared with wild-type (WT) Synechocystis. Metabolic phenotyping revealed accumulation of 2 phosphoglycolate (2PG) in DeltaccmM and of glycolate in DeltaglcD1/D2 in LC- but also in high inorganic carbon (HC)-grown mutant cells. The accumulation of photorespiratory metabolites provided evidence for the oxygenase activity of RubisCO at HC. The global gene expression patterns of HC-grown DeltaccmM and DeltaglcD1/D2 showed differential expression of many genes involved in photosynthesis, high-light stress and N assimilation. In contrast, the transcripts of LC-specific genes, such as those for inorganic carbon transporters and components of the carbon-concentrating mechanism (CCM), remained unchanged in HC cells. After a shift to LC, DeltaglcD1/D2 and WT cells displayed induction of many of the LC-inducible genes, whereas DeltaccmM lacked similar changes in expression. From the coincidence of the presence of 2PG in DeltaccmM without CCM induction and of glycolate in DeltaglcD1/D2 with CCM induction, we regard a direct role for 2PG as a metabolic signal for the induction of CCM during LC acclimation as less likely. Instead, our data suggest a potential role for glycolate as a signal molecule for enhanced expression of CCM genes. PMID- 22096151 TI - Escherichia coli enterobactin synthesis and uptake mutants are hypersensitive to an antimicrobial peptide that limits the availability of iron in addition to blocking Holliday junction resolution. AB - The peptide wrwycr inhibits Holliday junction resolution and is a potent antimicrobial. To study the physiological effects of wrwycr treatment on Escherichia coli cells, we partially screened the Keio collection of knockout mutants for those with increased sensitivity to wrwycr. Strains lacking part of the ferric-enterobactin (iron-bound siderophore) uptake and utilization system, parts of the enterobactin synthesis pathway, TolC (an outer-membrane channel protein) or Fur (an iron-responsive regulator) were hypersensitive to wrwycr. We provide evidence that the DeltatolC mutant was hypersensitive to wrwycr due to its reduced ability to efflux wrwycr from the cell rather than due to its export of newly synthesized enterobactin. Deleting ryhB, which encodes a small RNA involved in iron regulation, mostly relieved the wrwycr hypersensitivity of the fur and ferric-enterobactin uptake mutants, indicating that the altered regulation of a RyhB-controlled gene was at least partly responsible for the hypersensitivity of these strains. Chelatable iron in the cell, measured by electron paramagnetic resonance spectroscopy, increased dramatically following wrwycr treatment, as did expression of Fur-repressed genes and, to some extent, mutation frequency. These incongruous results suggest that while wrwycr treatment caused accumulation of chelatable iron in the cell, iron was not available to bind to Fur. This is corroborated by the observed induction of the suf system, which assembles iron-sulfur clusters in low-iron conditions. Disruption of iron metabolism by wrwycr, in addition to its effects on DNA repair, may make it a particularly effective antimicrobial in the context of the low-iron environment of a mammalian host. PMID- 22096152 TI - Effect of external voltage on Pseudomonas putida F1 in a bio electrochemical cell using toluene as sole carbon and energy source. AB - A bio electrochemical cell (BEC) was constructed as a typical two-chamber microbial fuel cell (MFC), except that it was operated under external voltage instead of constant resistance as in an MFC. The anode chamber contained a pure culture of Pseudomonas putida F1 grown in a minimal medium containing toluene as the sole carbon and energy source. Operating the BEC under external voltages of 75, 125, 175, 250 and 500 mV (versus an Ag/AgCl reference electrode) led to increased bacterial cell growth to an OD(600) of 0.62-0.75, while the control BEC, which was not connected to external voltage, reached an OD(600) of only 0.3. Examination of the current generated under external voltages of 75, 125, 175, 250 and 500 mV showed that the maximal currents were 11, 23, 28, 54 and 94 mA m(-2), respectively. Cyclic voltammetry experiments demonstrated an anodic peak at 270 mV, which may imply oxidation of a vital molecule. The average residual toluene concentration after 147 h in the BEC operated under external voltage was 22 %, whereas in the control BEC it was 81 %. Proteome analysis of bacterial cells grown in the BEC (125 mV) revealed two groups of proteins, which are ascribed to charge transfer in the bacterial cells and from the cell to the electrode. In conclusion, operating the BEC at 75-500 mV enabled growth of a pure culture of P. putida F1 and toluene degradation even in an oxygen-limited environment. PMID- 22096153 TI - The energy research imperative. PMID- 22096158 TI - U.S. research funding. NSF creates fast track for out-of-the-box proposals. PMID- 22096159 TI - U.S. Congress. Research projects could be roadkill in revision of massive highway bill. PMID- 22096160 TI - Scientific community. Revolution brings new hopes for Libyan archaeology. PMID- 22096161 TI - Climate change. China looks to balance its carbon books. PMID- 22096162 TI - Climate change. An unsung carbon sink. PMID- 22096163 TI - Ecology. Will busting dams boost salmon? PMID- 22096164 TI - Ecology. Out of the frying pan? PMID- 22096165 TI - Evolutionary biology. Evolutionary time travel. PMID- 22096166 TI - Natural resources. Dreams of a lithium empire. PMID- 22096167 TI - Race disparity in grants: check the citations. PMID- 22096168 TI - Race disparity in grants: empirical solutions vital. PMID- 22096170 TI - Race disparity in grants: oversight at home. PMID- 22096173 TI - Comment on "Global trends in wind speed and wave height". AB - Young et al. (Reports, 22 April 2011, p. 451) reported trends in global mean wind speed much larger than found by other investigators. Their report fails to reference these other investigations and does not discuss the consequences that such large wind trends would have on global evaporation and precipitation. The difference between their altimeter and buoy trends suggests a relatively large trend error. PMID- 22096175 TI - Environment and development. Preparing to manage climate change financing. PMID- 22096176 TI - Psychology. When more is more. PMID- 22096177 TI - Geography. Understanding tribal fates. PMID- 22096178 TI - Neuroscience. Human locomotor circuits conform. PMID- 22096179 TI - Biochemistry. One atom makes all the difference. PMID- 22096180 TI - Microbiology. Antioxidant strategies to tolerate antibiotics. PMID- 22096181 TI - Astronomy. Analyzing solar cycles. PMID- 22096183 TI - Retrospective. Steven P. Jobs (1955-2011). PMID- 22096182 TI - Materials science. True performance metrics in electrochemical energy storage. PMID- 22096184 TI - Materials for grid energy. Electricity now and when. Introduction. PMID- 22096185 TI - Saving for a rainy day. PMID- 22096186 TI - Turning over a new leaf. PMID- 22096187 TI - Sunlight in your tank--right away. PMID- 22096188 TI - Electrical energy storage for the grid: a battery of choices. AB - The increasing interest in energy storage for the grid can be attributed to multiple factors, including the capital costs of managing peak demands, the investments needed for grid reliability, and the integration of renewable energy sources. Although existing energy storage is dominated by pumped hydroelectric, there is the recognition that battery systems can offer a number of high-value opportunities, provided that lower costs can be obtained. The battery systems reviewed here include sodium-sulfur batteries that are commercially available for grid applications, redox-flow batteries that offer low cost, and lithium-ion batteries whose development for commercial electronics and electric vehicles is being applied to grid storage. PMID- 22096189 TI - Lowering the temperature of solid oxide fuel cells. AB - Fuel cells are uniquely capable of overcoming combustion efficiency limitations (e.g., the Carnot cycle). However, the linking of fuel cells (an energy conversion device) and hydrogen (an energy carrier) has emphasized investment in proton-exchange membrane fuel cells as part of a larger hydrogen economy and thus relegated fuel cells to a future technology. In contrast, solid oxide fuel cells are capable of operating on conventional fuels (as well as hydrogen) today. The main issue for solid oxide fuel cells is high operating temperature (about 800 degrees C) and the resulting materials and cost limitations and operating complexities (e.g., thermal cycling). Recent solid oxide fuel cells results have demonstrated extremely high power densities of about 2 watts per square centimeter at 650 degrees C along with flexible fueling, thus enabling higher efficiency within the current fuel infrastructure. Newly developed, high conductivity electrolytes and nanostructured electrode designs provide a path for further performance improvement at much lower temperatures, down to ~350 degrees C, thus providing opportunity to transform the way we convert and store energy. PMID- 22096190 TI - Evidence for interstitial carbon in nitrogenase FeMo cofactor. AB - The identity of the interstitial light atom in the center of the FeMo cofactor of nitrogenase has been enigmatic since its discovery. Atomic-resolution x-ray diffraction data and an electron spin echo envelope modulation (ESEEM) analysis now provide direct evidence that the ligand is a carbon species. PMID- 22096191 TI - The large, oxygen-rich halos of star-forming galaxies are a major reservoir of galactic metals. AB - The circumgalactic medium (CGM) is fed by galaxy outflows and accretion of intergalactic gas, but its mass, heavy element enrichment, and relation to galaxy properties are poorly constrained by observations. In a survey of the outskirts of 42 galaxies with the Cosmic Origins Spectrograph onboard the Hubble Space Telescope, we detected ubiquitous, large (150-kiloparsec) halos of ionized oxygen surrounding star-forming galaxies; we found much less ionized oxygen around galaxies with little or no star formation. This ionized CGM contains a substantial mass of heavy elements and gas, perhaps far exceeding the reservoirs of gas in the galaxies themselves. Our data indicate that it is a basic component of nearly all star-forming galaxies that is removed or transformed during the quenching of star formation and the transition to passive evolution. PMID- 22096192 TI - The hidden mass and large spatial extent of a post-starburst galaxy outflow. AB - Outflowing winds of multiphase plasma have been proposed to regulate the buildup of galaxies, but key aspects of these outflows have not been probed with observations. By using ultraviolet absorption spectroscopy, we show that "warm hot" plasma at 10(5.5) kelvin contains 10 to 150 times more mass than the cold gas in a post-starburst galaxy wind. This wind extends to distances > 68 kiloparsecs, and at least some portion of it will escape. Moreover, the kinematical correlation of the cold and warm-hot phases indicates that the warm hot plasma is related to the interaction of the cold matter with a hotter (unseen) phase at >>10(6) kelvin. Such multiphase winds can remove substantial masses and alter the evolution of post-starburst galaxies. PMID- 22096193 TI - Giant piezoelectricity on Si for hyperactive MEMS. AB - Microelectromechanical systems (MEMS) incorporating active piezoelectric layers offer integrated actuation, sensing, and transduction. The broad implementation of such active MEMS has long been constrained by the inability to integrate materials with giant piezoelectric response, such as Pb(Mg(1/3)Nb(2/3))O(3) PbTiO(3) (PMN-PT). We synthesized high-quality PMN-PT epitaxial thin films on vicinal (001) Si wafers with the use of an epitaxial (001) SrTiO(3) template layer with superior piezoelectric coefficients (e(31,f) = -27 +/- 3 coulombs per square meter) and figures of merit for piezoelectric energy-harvesting systems. We have incorporated these heterostructures into microcantilevers that are actuated with extremely low drive voltage due to thin-film piezoelectric properties that rival bulk PMN-PT single crystals. These epitaxial heterostructures exhibit very large electromechanical coupling for ultrasound medical imaging, microfluidic control, mechanical sensing, and energy harvesting. PMID- 22096194 TI - Ultralight metallic microlattices. AB - Ultralight (<10 milligrams per cubic centimeter) cellular materials are desirable for thermal insulation; battery electrodes; catalyst supports; and acoustic, vibration, or shock energy damping. We present ultralight materials based on periodic hollow-tube microlattices. These materials are fabricated by starting with a template formed by self-propagating photopolymer waveguide prototyping, coating the template by electroless nickel plating, and subsequently etching away the template. The resulting metallic microlattices exhibit densities rho >= 0.9 milligram per cubic centimeter, complete recovery after compression exceeding 50% strain, and energy absorption similar to elastomers. Young's modulus E scales with density as E ~ rho(2), in contrast to the E ~ rho(3) scaling observed for ultralight aerogels and carbon nanotube foams with stochastic architecture. We attribute these properties to structural hierarchy at the nanometer, micrometer, and millimeter scales. PMID- 22096195 TI - Silica-like malleable materials from permanent organic networks. AB - Permanently cross-linked materials have outstanding mechanical properties and solvent resistance, but they cannot be processed and reshaped once synthesized. Non-cross-linked polymers and those with reversible cross-links are processable, but they are soluble. We designed epoxy networks that can rearrange their topology by exchange reactions without depolymerization and showed that they are insoluble and processable. Unlike organic compounds and polymers whose viscosity varies abruptly near the glass transition, these networks show Arrhenius-like gradual viscosity variations like those of vitreous silica. Like silica, the materials can be wrought and welded to make complex objects by local heating without the use of molds. The concept of a glass made by reversible topology freezing in epoxy networks can be readily scaled up for applications and generalized to other chemistries. PMID- 22096196 TI - Domain dynamics during ferroelectric switching. AB - The utility of ferroelectric materials stems from the ability to nucleate and move polarized domains using an electric field. To understand the mechanisms of polarization switching, structural characterization at the nanoscale is required. We used aberration-corrected transmission electron microscopy to follow the kinetics and dynamics of ferroelectric switching at millisecond temporal and subangstrom spatial resolution in an epitaxial bilayer of an antiferromagnetic ferroelectric (BiFeO(3)) on a ferromagnetic electrode (La(0.7)Sr(0.3)MnO(3)). We observed localized nucleation events at the electrode interface, domain wall pinning on point defects, and the formation of ferroelectric domains localized to the ferroelectric and ferromagnetic interface. These results show how defects and interfaces impede full ferroelectric switching of a thin film. PMID- 22096197 TI - Negative frequency-dependent selection of sexually antagonistic alleles in Myodes glareolus. AB - Sexually antagonistic genetic variation, where optimal values of traits are sex dependent, is known to slow the loss of genetic variance associated with directional selection on fitness-related traits. However, sexual antagonism alone is not sufficient to maintain variation indefinitely. Selection of rare forms within the sexes can help to conserve genotypic diversity. We combined theoretical models and a field experiment with Myodes glareolus to show that negative frequency-dependent selection on male dominance maintains variation in sexually antagonistic alleles. In our experiment, high-dominance male bank voles were found to have low-fecundity sisters, and vice versa. These results show that investigations of sexually antagonistic traits should take into account the effects of social interactions on the interplay between ecology and evolution, and that investigations of genetic variation should not be conducted solely under laboratory conditions. PMID- 22096198 TI - X-ray emission spectroscopy evidences a central carbon in the nitrogenase iron molybdenum cofactor. AB - Nitrogenase is a complex enzyme that catalyzes the reduction of dinitrogen to ammonia. Despite insight from structural and biochemical studies, its structure and mechanism await full characterization. An iron-molybdenum cofactor (FeMoco) is thought to be the site of dinitrogen reduction, but the identity of a central atom in this cofactor remains unknown. Fe Kbeta x-ray emission spectroscopy (XES) of intact nitrogenase MoFe protein, isolated FeMoco, and the FeMoco-deficient nifB protein indicates that among the candidate atoms oxygen, nitrogen, and carbon, it is carbon that best fits the XES data. The experimental XES is supported by computational efforts, which show that oxidation and spin states do not affect the assignment of the central atom to C(4-). Identification of the central atom will drive further studies on its role in catalysis. PMID- 22096199 TI - Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 A resolution. AB - Gene silencing is essential for regulating cell fate in eukaryotes. Altered chromatin architectures contribute to maintaining the silenced state in a variety of species. The silent information regulator (Sir) proteins regulate mating type in Saccharomyces cerevisiae. One of these proteins, Sir3, interacts directly with the nucleosome to help generate silenced domains. We determined the crystal structure of a complex of the yeast Sir3 BAH (bromo-associated homology) domain and the nucleosome core particle at 3.0 angstrom resolution. We see multiple molecular interactions between the protein surfaces of the nucleosome and the BAH domain that explain numerous genetic mutations. These interactions are accompanied by structural rearrangements in both the nucleosome and the BAH domain. The structure explains how covalent modifications on H4K16 and H3K79 regulate formation of a silencing complex that contains the nucleosome as a central component. PMID- 22096200 TI - Active starvation responses mediate antibiotic tolerance in biofilms and nutrient limited bacteria. AB - Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance. Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections. PMID- 22096201 TI - H2S: a universal defense against antibiotics in bacteria. AB - Many prokaryotic species generate hydrogen sulfide (H(2)S) in their natural environments. However, the biochemistry and physiological role of this gas in nonsulfur bacteria remain largely unknown. Here we demonstrate that inactivation of putative cystathionine beta-synthase, cystathionine gamma-lyase, or 3 mercaptopyruvate sulfurtransferase in Bacillus anthracis, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli suppresses H(2)S production, rendering these pathogens highly sensitive to a multitude of antibiotics. Exogenous H(2)S suppresses this effect. Moreover, in bacteria that normally produce H(2)S and nitric oxide, these two gases act synergistically to sustain growth. The mechanism of gas-mediated antibiotic resistance relies on mitigation of oxidative stress imposed by antibiotics. PMID- 22096202 TI - Locomotor primitives in newborn babies and their development. AB - How rudimentary movements evolve into sophisticated ones during development remains unclear. It is often assumed that the primitive patterns of neural control are suppressed during development, replaced by entirely new patterns. Here we identified the basic patterns of lumbosacral motoneuron activity from multimuscle recordings in stepping neonates, toddlers, preschoolers, and adults. Surprisingly, we found that the two basic patterns of stepping neonates are retained through development, augmented by two new patterns first revealed in toddlers. Markedly similar patterns were observed also in the rat, cat, macaque, and guineafowl, consistent with the hypothesis that, despite substantial phylogenetic distances and morphological differences, locomotion in several animal species is built starting from common primitives, perhaps related to a common ancestral neural network. PMID- 22096203 TI - Rational choice, context dependence, and the value of information in European starlings (Sturnus vulgaris). AB - Both human and nonhuman decision-makers can deviate from optimal choice by making context-dependent choices. Because ignoring context information can be beneficial, this is called a "less-is-more effect." The fact that organisms are so sensitive to the context is thus paradoxical and calls for the inclusion of an ecological perspective. In an experiment with starlings, adding cues that identified the context impaired performance in simultaneous prey choices but improved it in sequential prey encounters, in which subjects could reject opportunities in order to search instead in the background. Because sequential prey encounters are likely to be more frequent in nature, storing and using contextual information appears to be ecologically rational on balance by conditioning acceptance of each opportunity to the relative richness of the background, even if this causes context-dependent suboptimal preferences in (less frequent) simultaneous choices. In ecologically relevant scenarios, more information seems to be more. PMID- 22096204 TI - The impact of Asian American value systems on palliative care: illustrative cases from the family-focused grief therapy trial. AB - BACKGROUND: Clinicians meet people from different ethnic backgrounds, yet need to respond in culturally sensitive ways. This article focuses on Asian American families. METHODS: Within a randomized controlled trial of family therapy commenced during palliative care and continued into bereavement, 3 families of Asian American background were examined qualitatively from a cultural perspective by listening to recordings of 26 therapy sessions and reviewing detailed supervision notes compiled by each therapist. RESULTS: A synopsis of each family's therapy narrative is presented. Prominent themes include family closeness, respect for hierarchy within the family, gender-determined roles, intergenerational tensions, preoccupation with shame and limited emotional expressiveness. CONCLUSIONS: Family therapists working with culturally diverse families need to pay thoughtful attention to ethnic issues as they strive to support them during palliative care and bereavement. PMID- 22096205 TI - The challenge of fungal keratitis. PMID- 22096206 TI - High levels of serum uric acid predict severity of coronary artery disease in patients with acute coronary syndrome. AB - We aimed to elucidate the relation between serum uric acid (SUA) level and severity of coronary artery disease (CAD) in nondiabetic, nonhypertensive patients (n = 246) with acute coronary syndrome (ACS). Severity of CAD was assessed by the Gensini score. One, 2, and 3 or more diseased vessels were identified in 87 (35.4%), 55 (22.4%), and 104 (42.2%) patients, respectively. Patients with hyperuricemia had higher Gensini score, high number of diseased vessels, critical lesions, and total occlusion. Serum uric acid level was significantly associated with number of diseased vessels. Serum uric acid was an independent risk factor for multivessel disease by univariate analysis. High levels of SUA associated with the severity of CAD in nondiabetic, nonhypertensive patients with ACS. PMID- 22096207 TI - Serum N-terminal pro-B-type natriuretic peptide levels are associated with functional capacity in patients with peripheral arterial disease. AB - We hypothesized that higher serum levels of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) are associated with lower functional capacity in patients with peripheral arterial disease ([PAD] n = 481, mean age 67, 68% men). Functional capacity was quantified as distance walked on a treadmill for 5 minutes. Patients were divided into 3 groups according to the distance walked: >144 yards (group 1, n = 254); 60 to 144 yards (group 2, n = 80); <60 yards or did not walk (group 3, n = 147). The association between NT-pro-BNP levels and the ordinal 3-level walking distance was assessed using multivariable ordinal logistic regression analyses that adjusted for several possible confounding variables. Higher levels of NT-pro-BNP were associated with a lower ordinal walking category independent of possible confounders (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.28-1.77; P < .001). In conclusion, higher levels of NT pro-BNP are independently associated with lower functional capacity in patients with PAD and may be a marker of hemodynamic stress in these patients. PMID- 22096208 TI - Counterpoint: high altitude is not for the birds! PMID- 22096209 TI - Rebuttal from Meir et al. PMID- 22096210 TI - Rebuttal from Llanos et al. PMID- 22096211 TI - Comments on point: counterpoint: high altitude is/is not for the birds! PMID- 22096212 TI - Last word on point:counterpoint: high altitude is/is not for the birds! PMID- 22096213 TI - Last word on point:counterpoint: high altitude is/is not for the birds! PMID- 22096214 TI - Impulsivity and the sexes: measurement and structural invariance of the UPPS-P Impulsive Behavior Scale. AB - Before it is possible to test whether men and women differ in impulsivity, it is necessary to evaluate whether impulsivity measures are invariant across sex. The UPPS-P Impulsive Behavior Scale (negative urgency, lack of premeditation, lack of perseverance, and sensation seeking, with added subscale of positive urgency) is one measure of five dispositions toward rash action that has shown to have robust and clinically useful relationships among risk-taking outcomes. In the current research, the author examined (a) the psychometric measurement invariance of the UPPS-P across sex, (b) the scale's structural invariance across sex, and (c) whether the five impulsivity traits differentially relate to risk outcomes as a function of sex. In a sample of 1,372 undergraduates, the author found evidence for measurement and invariance across sex: Thus, comparisons of men and women on the UPPS-P can be considered valid. Additionally, although males tend to report higher levels of sensation seeking and positive urgency (and possibly lack of perseverance), the relationships between the UPPS-P traits and risk outcomes were generally invariant across sex. The UPPS-P appears to function comparably across males and females, and mean differences on this scale between the sexes can be thought to reflect trait-level differences. PMID- 22096215 TI - The Expansion of mtDNA Haplogroup L3 within and out of Africa. AB - Although fossil remains show that anatomically modern humans dispersed out of Africa into the Near East ~100 to 130 ka, genetic evidence from extant populations has suggested that non-Africans descend primarily from a single successful later migration. Within the human mitochondrial DNA (mtDNA) tree, haplogroup L3 encompasses not only many sub-Saharan Africans but also all ancient non-African lineages, and its age therefore provides an upper bound for the dispersal out of Africa. An analysis of 369 complete African L3 sequences places this maximum at ~70 ka, virtually ruling out a successful exit before 74 ka, the date of the Toba volcanic supereruption in Sumatra. The similarity of the age of L3 to its two non-African daughter haplogroups, M and N, suggests that the same process was likely responsible for both the L3 expansion in Eastern Africa and the dispersal of a small group of modern humans out of Africa to settle the rest of the world. The timing of the expansion of L3 suggests a link to improved climatic conditions after ~70 ka in Eastern and Central Africa rather than to symbolically mediated behavior, which evidently arose considerably earlier. The L3 mtDNA pool within Africa suggests a migration from Eastern Africa to Central Africa ~60 to 35 ka and major migrations in the immediate postglacial again linked to climate. The largest population size increase seen in the L3 data is 3 4 ka in Central Africa, corresponding to Bantu expansions, leading diverse L3 lineages to spread into Eastern and Southern Africa in the last 3-2 ka. PMID- 22096216 TI - Miniature inverted-repeat transposable elements (MITEs) have been accumulated through amplification bursts and play important roles in gene expression and species diversity in Oryza sativa. AB - Miniature inverted-repeat transposable elements (MITEs) are predicted to play important roles on genome evolution. We developed a BLASTN-based approach for de novo identification of MITEs and systematically analyzed MITEs in rice genome. The genome of rice cultivar Nipponbare (Oryza sativa ssp. japonica) harbors 178,533 MITE-related sequences classified into 338 families. Pairwise nucleotide diversity and phylogenetic tree analysis indicated that individual MITE families were resulted from one or multiple rounds of amplification bursts. The timing of amplification burst varied considerably between different MITE families or subfamilies. MITEs are associated with 23,623 (58.2%) genes in rice genome. At least 7,887 MITEs are transcribed and more than 3,463 were transcribed with rice genes. The MITE sequences transcribed with rice coding genes form 1,130 pairs of potential natural sense/antisense transcripts. MITEs generate 23.5% (183,837 of 781,885) of all small RNAs identified from rice. Some MITE families generated small RNAs mainly from the terminals, while other families generated small RNAs predominantly from the central region. More than half (51.8%) of the MITE-derived small RNAs were generated exclusively by MITEs located away from genes. Genome wide analysis showed that genes associated with MITEs have significantly lower expression than genes away from MITEs. Approximately 14.8% of loci with full length MITEs have presence/absence polymorphism between rice cultivars 93-11 (O. sativa ssp. indica) and Nipponbare. Considering that different sets of genes may be regulated by MITE-derived small RNAs in different genotypes, MITEs provide considerable diversity for O. sativa. PMID- 22096217 TI - Dosimetric variations of target volumes and organs at risk in nasopharyngeal carcinoma intensity-modulated radiotherapy. AB - OBJECTIVE: The aim of this study was to evaluate the actual dose variability to the targets and organs at risk (OARs) during nasopharyngeal carcinoma (NPC) intensity-modulated radiotherapy (IMRT) and to investigate the significance of replanning. METHODS: 11 NPC patients were included in this study. Each patient had both a planning CT and weekly repeated CT. Simulated plans that were generated by using the same beam configurations mapped to the repeated CT represented the actual delivered doses to the target volumes and OARs. An IMRT replanning was performed with the fifth week CT scan. Doses among the initial plan, the simulated plans and replanning were compared. RESULTS: There were no significant dosimetric differences in the gross tumour volume, clinical target volume (CTV) 1 or CTV2 for either the simulated plans or the replanning compared with the initial plan. Dosimetric variability of both parotid glands and the brain stem were unique to each individual, and doses to the spinal cord were always maintained within the limit. Replanning in the fifth week had significantly decreased the doses delivered to both parotids (p-values of the mean dose were 0.015 and 0.026 for the left and right parotid, respectively), whereas it did not reduce the doses to the brain stem and spinal cord. There was no relationship between dose variability and weight loss. CONCLUSIONS: There are no significant dose changes for target volumes and spinal cord, and doses to the brain stem and both parotid glands changed individually during NPC IMRT. Replanning helps to spare bilateral parotids. PMID- 22096218 TI - Diagnostic quality of 50 and 100 MUm computed radiography compared with screen film mammography in operative breast specimens. AB - OBJECTIVE: To compare reader ratings of the clinical diagnostic quality of 50 and 100 MUm computed radiography (CR) systems with screen-film mammography (SFM) in operative specimens. METHODS: Mammograms of 57 fresh operative breast specimens were analysed by 10 readers. Exposures were made with identical position and compression with three mammographic systems (Fuji 100CR, 50CR and SFM). Images were anonymised and readers blinded to the CR system used. A five-point comparative scoring system (-2 to +2) was used to assess seven quality criteria and overall diagnostic value. Statistical analysis was subsequently performed of reader ratings (n = 16,925). RESULTS: For most quality criteria, both CR systems were rated as equivalent to or better than SFM. The CR systems were significantly better at demonstrating skin edge and background tissue (p < 1 * 10(-5)). Microcalcification was best demonstrated on the CR50 system (p < 1 * 10(-5)). The overall diagnostic value of both CR systems was rated as being as good as or better than SFM (p < 1 * 10(-5)). CONCLUSION: In this clinical setting, the overall diagnostic performance of both CR systems was as good as or better than SFM, with the CR50 system performing better than the CR100. PMID- 22096219 TI - Spleen in haematological malignancies: spectrum of imaging findings. AB - Imaging morphology and metabolic activity of splenic lesions is of paramount importance in patients with haematological malignancies; it can alter tumour staging, treatment protocols and overall prognosis. CT, MRI and positron emission tomography (PET)/CT have been shown to be powerful tools for the non-invasive assessment of splenic involvement in various haematological malignancies. Since many haematological malignancies and non-neoplastic conditions can involve the spleen and imaging manifestations can overlap, imaging and clinical findings outside of the spleen should be looked for to narrow the differential diagnosis; confirmation can be obtained by pathological findings. Radiologists should be familiar with the cross-sectional imaging patterns of haematological malignancies involving the spleen as well as non-neoplastic splenic findings common in these patients to facilitate their care and follow-up. This pictorial review provides the common and uncommon imaging appearances and complications of various haematological malignancies involving the spleen on CT, MRI and PET/CT, and common pitfalls in diagnosis. PMID- 22096220 TI - More harm than good? The anatomy of misguided shielding of the ovaries. AB - OBJECTIVE: Popular gonad shield designs aim to provide coverage of the true pelvis, which is presumed to be the probable location of the ovaries. Shields are frequently placed inaccurately, especially in children, obscuring important orthopaedic landmarks on pelvic radiographs. We aimed to identify the position of the ovaries and asses how this may vary with age and the degree of bladder filling. We aimed to identify the position of the ovaries and asses how this may vary with age and the degree of bladder filling. METHODS: Using MRI examinations of the pelvis in women and children, we located 594 ovaries in 306 female patients aged from birth to 59 years. RESULTS: This study provides new evidence that bladder filling affects ovary position. A lower than expected number of patients had both ovaries within the pelvis if the bladder contained more than a moderate volume of urine. Bladder emptying should be achieved wherever practical if a shield is used. In children under the age of 7 years, more than half (19/37) had at least one ovary outside the true pelvis. There was a significant association between age and ovary position, with the percentage of patients with one or both ovaries outside the true pelvis decreasing with age (chi(2), p<0.0001). CONCLUSION: The embryological descent of the ovaries into the pelvis would appear to continue after birth, well into childhood. Current popular shield designs are therefore inappropriate for use in young children. Given the high risk of obscuring critical landmarks, coupled with the new evidence that even accurate placement will not necessarily protect the ovaries, the use of pelvic shields in girls should be reconsidered. PMID- 22096221 TI - Imaging carotid body chemodectomas with 68Ga-DOTA-NOC PET-CT. AB - OBJECTIVE: The purpose of the present study was to evaluate the role of 68 gallium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-1-Nal3 octreotide ((68)Ga-DOTA-NOC) positron emission tomography CT (PET-CT) in carotid body chemodectomas (CBCs). METHODS: 5 patients with known CBCs (conventional imaging and angiography) were evaluated retrospectively (3 males, 2 females; mean age 36.6 years). All underwent PET-CT after injection of 148 MBq (4 mCi) of (68)Ga-DOTA-NOC. RESULTS: At baseline there were four bilateral CBCs and one unilateral CBC with an additional glomus tympanicum and bilateral glomus jugulare tumour in these five patients. All these lesions showed intense uptake on (68)Ga DOTA-NOC PET-CT. Apart from these known lesions, additional tumours were detected in three patients; glomus jugulare in one, aortic body tumour and multiple abdominal paragangliomas in another and unsuspected vertebral metastasis in the last. Overall it led to a change in management in 3 of the 5 patients (60%). CONCLUSION: (68)Ga-DOTA-NOC PET-CT is a promising non-invasive imaging modality in the detection and characterisation of CBCs. PMID- 22096222 TI - Comparison of the clinical performance of three digital mammography systems in a breast cancer screening programme. AB - This study compares the clinical performance of three digital mammography system types in a breast cancer screening programme. 28 digital mammography systems from three different vendors were included in the study. The retrospective analysis included 238 182 screening examinations of females aged between 50 and 64 years over a 3-year period. All images were double read and assigned a result according to a 5-point rating scale to indicate the probability of cancer. Females with a positive result were recalled for further assessment imaging and biopsy if necessary. Clinical performance in terms of cancer detection rate was analysed and the results presented. No statistically significant difference was found between the three different mammography systems in a population-based screening programme, in terms of the overall cancer detection rate or in the detection of invasive cancer and ductal carcinoma in situ. This was shown in both prevalent and subsequent screening examination categories. The results demonstrate comparable cancer detection performance for the three imaging system types operational in the screening programme. PMID- 22096223 TI - Enhancement of the radiation response of EMT-6 tumours by a copper octabromotetracarboranylphenylporphyrin. AB - OBJECTIVE: The carborane-containing porphyrin, copper (II) 2,3,7,8,12,13,17,18 octabromo-5,10,15,20-tetrakis(3-[1,2-dicarba-closo-dodecaboranyl]methoxyphenyl) porphyrin (CuTCPBr), was investigated as a potential radiation enhancing agent for X-ray radiotherapy (XRT) in a subcutaneously implanted EMT-6 murine carcinoma. METHOD: The biodistribution and toxicological profile of this porphyrin has been shown to be favourable for another bimodal radiotherapy technique, boron neutron-capture therapy. For the XRT studies, CuTCPBr was formulated in either 9% Cremophor (BASF Corporation, Ludwigschafen, Germany) EL and 18% propylene glycol (9% CRM) or a revised formulation comprising 1% Cremophor ELP, 2% Tween 80 (JT Baker, Mansfield, MA), 5% ethanol and 2.2% PEG 400 (CTEP formulation), which would be more clinically acceptable than the original 9% CRM formulation. Using the 9% CRM formulation of CuTCPBr, doses of 100, 210 or 400 mg kg(-1) of body weight were used in combination with single doses of 25-35 Gy 100 kVp X-rays. RESULTS: While doses of 100 mg kg(-1) and 210 mg kg(-1) did not result in any significant enhancement of tumour response, the 400 mg kg(-1) dose did. A dose modification factor of 1.20+/-0.10 was obtained based on the comparison of doses that produced a 50% local tumour control probability. With the CTEP formulation of CuTCPBr, doses of 83 and 170 mg kg(-1) produced significant radiation enhancement, with dose modification factors based on the TCP(50) of 1.29+/-0.15 and 1.84+/-0.24, respectively. CONCLUSION: CuTCPBr significantly enhanced the efficacy of XRT in the treatment of EMT-6 carcinomas in mice. The CTEP formulation showed a marked improvement, with over 9% CRM being associated with higher dose modification factors. Moreover, the radiation response in the skin was not enhanced. PMID- 22096224 TI - Prediction of incident hip fracture by femoral neck bone mineral density and neck shaft angle: a 5-year longitudinal study in post-menopausal females. AB - OBJECTIVE: To compare hip fracture incidence in post-menopausal females who were differently stratified for the fracture risk according to bone mineral density and proximal femur geometry. METHODS: In a 5 year follow-up study, the hip fracture incidence in 729 post-menopausal females (45 of whom suffered from incident hip fracture) was assessed and compared. Forward logistic regression was used to select independent predictors of hip fracture risk, including age, age at menopause, height, weight, femoral neck bone mineral density (FNBMD), neck-shaft angle (NSA), hip axis length, femoral neck diameter and femoral shaft diameter as covariates. Fracture incidence was then calculated for the categories of young/old age, high/low FNBMD and wide/narrow NSA, which were obtained by dichotomising each hip fracture independent predictor at the value best separating females with and without a hip fracture. RESULTS: The hip fracture incidence of the whole cohort was significantly higher in females with a wide NSA (8.52%) than in those with a narrow NSA (3.51%). The combination of wide NSA and low FNBMD had the highest hip fracture incidence in the whole cohort (17.61%) and each age category. The combinations of narrow/wide NSA with low/high FNBMD, respectively, gave a significantly higher fracture incidence in older than in younger women, whereas women with a combined wide NSA and low FNBMD had no significantly different fracture incidence in young (14.60%) or old age (21.62%). CONCLUSION: Our study showed that NSA is effective at predicting the hip fracture risk and that the detection in early post-menopause of a wide NSA together with a low FNBMD should identify females at high probability of incident hip fracture. PMID- 22096225 TI - Contrast-enhanced ultrasonography of hepatocellular carcinoma: correlation between quantitative parameters and histological grading. AB - OBJECTIVE: The quantitative parameters in the contrast-enhanced ultrasonography time-intensity curve of hepatocellular carcinoma (HCC) were studied to explore their possible implication for histological grading of HCC. METHODS: A total of 130 HCC patients (115 males and 15 females; age: 48.13+/-11.00 years) were studied using contrast-enhanced ultrasonography time-intensity curve and histological pathology. The quantification software Sonoliver(r) (TomTec Imaging Systems, Unterschleissheim, Germany) was applied to derive time-intensity curves of regions of interest in the interior of HCCs and in reference. Quantitative parameters of 115 patients were successfully obtained, including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), rise slope (RS) and washout time (WT). Histological grading of HCC was performed using haematoxylin-eosin staining, and monoclonal antibodies specific for smooth muscle actin were used to observe unpaired arteries (UAs). RESULTS: There were significant differences among WTs in the three differentiated HCC groups (p<0.05). However, there were no significant differences among RT, TTP, RS and IMAX in the differentiated HCC groups. Moreover, the number of UAs in the differentiated HCC groups showed no statistical significance. CONCLUSION: WT plays an important role in predicting well, moderately and poorly differentiated HCC. PMID- 22096226 TI - Characterization of the role of ABCG2 as a bile acid transporter in liver and placenta. AB - ABCG2 is involved in epithelial transport/barrier functions. Here, we have investigated its ability to transport bile acids in liver and placenta. Cholylglycylamido fluorescein (CGamF) was exported by WIF-B9/R cells, which do not express the bile salt export pump (BSEP). Sensitivity to typical inhibitors suggested that CGamF export was mainly mediated by ABCG2. In Chinese hamster ovary (CHO cells), coexpression of rat Oatp1a1 and human ABCG2 enhanced the uptake and efflux, respectively, of CGamF, cholic acid (CA), glycoCA (GCA), tauroCA, and taurolithocholic acid-3-sulfate. The ability of ABCG2 to export these bile acids was confirmed by microinjecting them together with inulin in Xenopus laevis oocytes expressing this pump. ABCG2-mediated bile acid transport was inhibited by estradiol 17beta-d-glucuronide and fumitremorgin C. Placental barrier for bile acids accounted for <2-fold increase in fetal cholanemia despite >14-fold increased maternal cholanemia induced by obstructive cholestasis in pregnant rats. In rat placenta, the expression of Abcg2, which was much higher than that of Bsep, was not affected by short-term cholestasis. In pregnant rats, fumitremorgin C did not affect uptake/secretion of GCA by the liver but inhibited its fetal-maternal transfer. Compared with wild-type mice, obstructive cholestasis in pregnant Abcg2(-/-) knockout mice induced similar bile acid accumulation in maternal serum but higher accumulation in placenta, fetal serum, and liver. In conclusion, ABCG2 is able to transport bile acids. The importance of this function depends on the relative expression in the same epithelium of other bile acid exporters. Thus, ABCG2 may play a key role in bile acid transport in placenta, as BSEP does in liver. PMID- 22096227 TI - MINT, the molecular interaction database: 2012 update. AB - The Molecular INTeraction Database (MINT, http://mint.bio.uniroma2.it/mint/) is a public repository for protein-protein interactions (PPI) reported in peer reviewed journals. The database grows steadily over the years and at September 2011 contains approximately 235,000 binary interactions captured from over 4750 publications. The web interface allows the users to search, visualize and download interactions data. MINT is one of the members of the International Molecular Exchange consortium (IMEx) and adopts the Molecular Interaction Ontology of the Proteomics Standard Initiative (PSI-MI) standards for curation and data exchange. MINT data are freely accessible and downloadable at http://mint.bio.uniroma2.it/mint/download.do. We report here the growth of the database, the major changes in curation policy and a new algorithm to assign a confidence to each interaction. PMID- 22096228 TI - SubtiWiki--a comprehensive community resource for the model organism Bacillus subtilis. AB - In the post-genomic era, most components of a cell are known and they can be quantified by large-scale functional genomics approaches. However, genome annotation is the bottleneck that hampers our understanding of living cells and organisms. Up-to-date functional annotation is of special importance for model organisms that provide a frame of reference for studies with other relevant organisms. We have generated a Wiki-type database for the Gram-positive model bacterium Bacillus subtilis, SubtiWiki (http://subtiwiki.uni-goettingen.de/). This Wiki is centered around the individual genes and gene products of B. subtilis and provides information on each aspect of gene function and expression as well as protein activity and its control. SubtiWiki is accompanied by two companion databases SubtiPathways and SubtInteract that provide graphical representations of B. subtilis metabolism and its regulation and of protein protein interactions, respectively. The diagrams of both databases are easily navigatable using the popular Google maps API, and they are extensively linked with the SubtiWiki gene pages. Moreover, each gene/gene product was assigned to one or more functional categories and transcription factor regulons. Pages for the specific categories and regulons provide a rapid overview of functionally related genes/proteins. Today, SubtiWiki can be regarded as one of the most complete inventories of knowledge on a living organism in one single resource. PMID- 22096229 TI - InterPro in 2011: new developments in the family and domain prediction database. AB - InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces. PMID- 22096230 TI - WikiPathways: building research communities on biological pathways. AB - Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein. WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further. PMID- 22096231 TI - eggNOG v3.0: orthologous groups covering 1133 organisms at 41 different taxonomic ranges. AB - Orthologous relationships form the basis of most comparative genomic and metagenomic studies and are essential for proper phylogenetic and functional analyses. The third version of the eggNOG database (http://eggnog.embl.de) contains non-supervised orthologous groups constructed from 1133 organisms, doubling the number of genes with orthology assignment compared to eggNOG v2. The new release is the result of a number of improvements and expansions: (i) the underlying homology searches are now based on the SIMAP database; (ii) the orthologous groups have been extended to 41 levels of selected taxonomic ranges enabling much more fine-grained orthology assignments; and (iii) the newly designed web page is considerably faster with more functionality. In total, eggNOG v3 contains 721,801 orthologous groups, encompassing a total of 4,396,591 genes. Additionally, we updated 4873 and 4850 original COGs and KOGs, respectively, to include all 1133 organisms. At the universal level, covering all three domains of life, 101,208 orthologous groups are available, while the others are applicable at 40 more limited taxonomic ranges. Each group is amended by multiple sequence alignments and maximum-likelihood trees and broad functional descriptions are provided for 450,904 orthologous groups (62.5%). PMID- 22096232 TI - The BioSample Database (BioSD) at the European Bioinformatics Institute. AB - The BioSample Database (http://www.ebi.ac.uk/biosamples) is a new database at EBI that stores information about biological samples used in molecular experiments, such as sequencing, gene expression or proteomics. The goals of the BioSample Database include: (i) recording and linking of sample information consistently within EBI databases such as ENA, ArrayExpress and PRIDE; (ii) minimizing data entry efforts for EBI database submitters by enabling submitting sample descriptions once and referencing them later in data submissions to assay databases and (iii) supporting cross database queries by sample characteristics. Each sample in the database is assigned an accession number. The database includes a growing set of reference samples, such as cell lines, which are repeatedly used in experiments and can be easily referenced from any database by their accession numbers. Accession numbers for the reference samples will be exchanged with a similar database at NCBI. The samples in the database can be queried by their attributes, such as sample types, disease names or sample providers. A simple tab-delimited format facilitates submissions of sample information to the database, initially via email to biosamples@ebi.ac.uk. PMID- 22096233 TI - MINAS--a database of Metal Ions in Nucleic AcidS. AB - Correctly folded into the respective native 3D structure, RNA and DNA are responsible for uncountable key functions in any viable organism. In order to exert their function, metal ion cofactors are closely involved in folding, structure formation and, e.g. in ribozymes, also the catalytic mechanism. The database MINAS, Metal Ions in Nucleic AcidS (http://www.minas.uzh.ch), compiles the detailed information on innersphere, outersphere and larger coordination environment of >70,000 metal ions of 36 elements found in >2000 structures of nucleic acids contained today in the PDB and NDB. MINAS is updated monthly with new structures and offers a multitude of search functions, e.g. the kind of metal ion, metal-ligand distance, innersphere and outersphere ligands defined by element or functional group, residue, experimental method, as well as PDB entry related information. The results of each search can be saved individually for later use with so-called miniPDB files containing the respective metal ion together with the coordination environment within a 15 A radius. MINAS thus offers a unique way to explore the coordination geometries and ligands of metal ions together with the respective binding pockets in nucleic acids. PMID- 22096234 TI - dbDEPC 2.0: updated database of differentially expressed proteins in human cancers. AB - A large amount of differentially expressed proteins (DEPs) have been identified in various cancer proteomics experiments, curation and annotation of these proteins are important in deciphering their roles in oncogenesis and tumor progression, and may further help to discover potential protein biomarkers for clinical applications. In 2009, we published the first database of DEPs in human cancers (dbDEPCs). In this updated version of 2011, dbDEPC 2.0 has more than doubly expanded to over 4000 protein entries, curated from 331 experiments across 20 types of human cancers. This resource allows researchers to search whether their interested proteins have been reported changing in certain cancers, to compare their own proteomic discovery with previous studies, to picture selected protein expression heatmap across multiple cancers and to relate protein expression changes with aberrance in other genetic level. New important developments include addition of experiment design information, advanced filter tools for customer-specified analysis and a network analysis tool. We expect dbDEPC 2.0 to be a much more powerful tool than it was in its first release and can serve as reference to both proteomics and cancer researchers. dbDEPC 2.0 is available at http://lifecenter.sgst.cn/dbdepc/index.do. PMID- 22096235 TI - Predictive networks: a flexible, open source, web application for integration and analysis of human gene networks. AB - Genomics provided us with an unprecedented quantity of data on the genes that are activated or repressed in a wide range of phenotypes. We have increasingly come to recognize that defining the networks and pathways underlying these phenotypes requires both the integration of multiple data types and the development of advanced computational methods to infer relationships between the genes and to estimate the predictive power of the networks through which they interact. To address these issues we have developed Predictive Networks (PN), a flexible, open source, web-based application and data services framework that enables the integration, navigation, visualization and analysis of gene interaction networks. The primary goal of PN is to allow biomedical researchers to evaluate experimentally derived gene lists in the context of large-scale gene interaction networks. The PN analytical pipeline involves two key steps. The first is the collection of a comprehensive set of known gene interactions derived from a variety of publicly available sources. The second is to use these 'known' interactions together with gene expression data to infer robust gene networks. The PN web application is accessible from http://predictivenetworks.org. The PN code base is freely available at https://sourceforge.net/projects/predictivenets/. PMID- 22096236 TI - ProOpDB: Prokaryotic Operon DataBase. AB - The Prokaryotic Operon DataBase (ProOpDB, http://operons.ibt.unam.mx/OperonPredictor) constitutes one of the most precise and complete repositories of operon predictions now available. Using our novel and highly accurate operon identification algorithm, we have predicted the operon structures of more than 1200 prokaryotic genomes. ProOpDB offers diverse alternatives by which a set of operon predictions can be retrieved including: (i) organism name, (ii) metabolic pathways, as defined by the KEGG database, (iii) gene orthology, as defined by the COG database, (iv) conserved protein domains, as defined by the Pfam database, (v) reference gene and (vi) reference operon, among others. In order to limit the operon output to non-redundant organisms, ProOpDB offers an efficient method to select the most representative organisms based on a precompiled phylogenetic distances matrix. In addition, the ProOpDB operon predictions are used directly as the input data of our Gene Context Tool to visualize their genomic context and retrieve the sequence of their corresponding 5' regulatory regions, as well as the nucleotide or amino acid sequences of their genes. PMID- 22096237 TI - Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: a role for human cytomegalovirus? AB - Natural killer (NK) cells play a crucial role in early immunity after hematopoietic stem cell transplantation because they are the first lymphocyte subset recovering after the allograft. In this study, we analyzed the development of NK cells after intrabone umbilical cord blood (CB) transplantation in 18 adult patients with hematologic malignancies. Our data indicate that, also in this transplantation setting, NK cells are the first lymphoid population detectable in peripheral blood. However, different patterns of NK-cell development could be identified. Indeed, in a group of patients, a relevant fraction of NK cells expressed a mature phenotype characterized by the KIR(+)NKG2A(-) signature 3-6 months after transplantation. In other patients, most NK cells maintained an immature phenotype even after 12 months. A possible role for cytomegalovirus in the promotion of NK-cell development was suggested by the observation that a more rapid NK-cell maturation together with expansion of NKG2C(+) NK cells was confined to patients experiencing cytomegalovirus reactivation. In a fraction of these patients, an aberrant and hyporesponsive CD56(-)CD16(+)p75/AIRM1(-) NK-cell subset (mostly KIR(+)NKG2A(-)) reminiscent of that described in patients with viremic HIV was detected. Our data support the concept that cytomegalovirus infection may drive NK-cell development after umbilical CB transplantation. PMID- 22096238 TI - Identification of VLDLR as a novel endothelial cell receptor for fibrin that modulates fibrin-dependent transendothelial migration of leukocytes. AB - While testing the effect of the (beta15-66)(2) fragment, which mimics a pair of fibrin betaN-domains, on the morphology of endothelial cells, we found that this fragment induces redistribution of vascular endothelial-cadherin in a process that is inhibited by the receptor-associated protein (RAP). Based on this finding, we hypothesized that fibrin may interact with members of RAP-dependent low-density lipoprotein (LDL) receptor family. To test this hypothesis, we examined the interaction of (beta15-66)(2), fibrin, and several fibrin-derived fragments with 2 members of this family by ELISA and surface plasmon resonance. The experiments showed that very LDL (VLDL) receptor (VLDLR) interacts with high affinity with fibrin through its betaN-domains, and this interaction is inhibited by RAP and (beta15-66)(2). Furthermore, RAP inhibited transendothelial migration of neutrophils induced by fibrin-derived NDSK-II fragment containing betaN domains, suggesting the involvement of VLDLR in fibrin-dependent leukocyte transmigration. Our experiments with VLDLR-deficient mice confirmed this suggestion by showing that, in contrast to wild-type mice, fibrin-dependent leukocyte transmigration does not occur in such mice. Altogether, the present study identified VLDLR as a novel endothelial cell receptor for fibrin that promotes fibrin-dependent leukocyte transmigration and thereby inflammation. Establishing the molecular mechanism underlying this interaction may result in the development of novel inhibitors of fibrin-dependent inflammation. PMID- 22096239 TI - Hematopoietic stem cell engineering at a crossroads. AB - The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead. PMID- 22096240 TI - Fetal hemoglobin levels and morbidity in untransfused patients with beta thalassemia intermedia. AB - To evaluate the association between fetal hemoglobin (HbF) levels and morbidity in beta-thalassemia intermedia (TI), we analyzed data from 63 untransfused patients who had also never received HbF induction therapy. Patient records were reviewed for any history of 10 predefined morbidities. Laboratory measurements for markers of ineffective erythropoiesis were also obtained. The mean age of patients was 32.1 years, 47.6% were males, and the median HbF level was 37.2%. HbF levels correlated positively with total hemoglobin, yet negatively with growth differentiation factor-15 and non-transferrin-bound iron levels. Median HbF levels were significantly lower in patients with the majority of evaluated morbidities than in those without. There was a strong negative adjusted linear correlation between the HbF level and the total number of morbidities (R(2) = 0.825, P < .001). The HbF threshold of 63.7% had 95.5% sensitivity and 100% specificity for ensuring absence of morbidity. There exists a strong association between HbF levels and morbidity in the subset of untransfused patients with TI. PMID- 22096241 TI - SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value. AB - SF3B1 mutations were recently reported in myelodysplastic syndromes (MDSs), especially in the presence of ring sideroblasts (RSs). We sought to define the interaction between SF3B1 mutations, morphology, karyotype, and prognosis in MDS with more than or equal to 15% RS (MDS-RS). We studied 107 patients with MDS-RS, including 48 with refractory anemia with RS (RARS), 43 with refractory cytopenia with multilineage dysplasia (RCMD)-RS, 11 with refractory anemia with excess blasts-1 (RAEB1)-RS, and 5 with RAEB2-RS. SF3B1 mutations were detected in 53 (~ 50%) patients: 35 RARS (73%), 16 RCMD-RS (37%), and 2 RAEB1-RS (18%). In univariate analysis, the presence of SF3B1 mutations was associated with better overall (P < .01) and leukemia-free (P < .01) survival; however, in both instances, significance was completely accounted for by World Health Organization morphologic risk categorization. In other words, when RARS and RCMD-RS were analyzed separately, there was no additional prognostic value from the presence or absence of SF3B1 mutations. PMID- 22096243 TI - EBV-associated T/NK-cell lymphoproliferative diseases in nonimmunocompromised hosts: prospective analysis of 108 cases. AB - EBV-associated T/NK-cell lymphoproliferative disease (T/NK-LPD) is defined as a systemic illness characterized by clonal proliferation of EBV-infected T or NK cells. We prospectively enrolled 108 nonimmunocompromised patients with this disease (50 men and 58 women; median onset age, 8 years; age range, 1-50 years) evidenced by expansion of EBV(+) T/NK cells in the peripheral blood; these were of the T-cell type in 64 cases and of the NK-cell type in 44, and were clinically categorized into 4 groups: 80 cases of chronic active EBV disease, 15 of EBV associated hemophagocytic lymphohistiocytosis, 9 of severe mosquito bite allergy, and 4 of hydroa vacciniforme. These clinical profiles were closely linked with the EBV(+) cell immunophenotypes. In a median follow-up period of 46 months, 47 patients (44%) died of severe organ complications. During the follow-up, 13 patients developed overt lymphoma or leukemia characterized by extranodal NK/T cell lymphoma and aggressive NK-cell leukemia. Fifty-nine received hematopoietic stem cell transplantation, 66% of whom survived. Age at onset of disease (>= 8 years) and liver dysfunction were risk factors for mortality, whereas patients who received transplantation had a better prognosis. These data depict clinical characteristics of systemic EBV(+) T/NK-LPD and provide insight into the diagnostic and therapeutic approaches for distinct disease. PMID- 22096242 TI - Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure. AB - The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSbeta degrees thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761. PMID- 22096244 TI - P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. AB - Interactions between multiple myeloma (MM) cells and the BM microenvironment play a critical role in the pathogenesis of MM and in the development of drug resistance by MM cells. Selectins are involved in extravasation and homing of leukocytes to target organs. In the present study, we focused on adhesion dynamics that involve P-selectin glycoprotein ligand-1 (PSGL-1) on MM cells and its interaction with selectins in the BM microenvironment. We show that PSGL-1 is highly expressed on MM cells and regulates the adhesion and homing of MM cells to cells in the BM microenvironment in vitro and in vivo. This interaction involves both endothelial cells and BM stromal cells. Using loss-of-function studies and the small-molecule pan-selectin inhibitor GMI-1070, we show that PSGL-1 regulates the activation of integrins and downstream signaling. We also document that this interaction regulates MM-cell proliferation in coculture with BM microenvironmental cells and the development of drug resistance. Furthermore, inhibiting this interaction with GMI-1070 enhances the sensitization of MM cells to bortezomib in vitro and in vivo. These data highlight the critical contribution of PSGL-1 to the regulation of growth, dissemination, and drug resistance in MM in the context of the BM microenvironment. PMID- 22096245 TI - miR-155 regulates HGAL expression and increases lymphoma cell motility. AB - HGAL, a prognostic biomarker in patients with diffuse large B-cell lymphoma and classic Hodgkin lymphoma, inhibits lymphocyte and lymphoma cell motility by activating the RhoA signaling cascade and interacting with actin and myosin proteins. Although HGAL expression is limited to germinal center (GC) lymphocytes and GC-derived lymphomas, little is known about its regulation. miR-155 is implicated in control of GC reaction and lymphomagenesis. We demonstrate that miR 155 directly down-regulates HGAL expression by binding to its 3'-untranslated region, leading to decreased RhoA activation and increased spontaneous and chemoattractant-induced lymphoma cell motility. The effects of miR-155 on RhoA activation and cell motility can be rescued by transfection of HGAL lacking the miR-155 binding site. This inhibitory effect of miR-155 suggests that it may have a key role in the loss of HGAL expression on differentiation of human GC B cells to plasma cell. Furthermore, this effect may contribute to lymphoma cell dissemination and aggressiveness, characteristic of activated B cell-like diffuse large B-cell lymphoma typically expressing high levels of miR-155 and lacking HGAL expression. PMID- 22096246 TI - In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling. AB - The mechanism by which thrombotic vessel occlusion occurs independently of plaque development or endothelial cell (EC) disruption remains unclear, largely because of an inability to visualize the formation of thrombus, especially at the single platelet level in real time. Here we demonstrate that rapidly developing thrombi composed of discoid platelets can be induced in the mesenteric capillaries, arterioles, and large-sized arteries of living mice, enabling characterization of the kinetics of thrombosis initiation and the multicellular interrelationships during thrombus development. Platelet aggregation without EC disruption was triggered by reactive oxygen species (ROS) photochemically induced by moderate power laser irradiation. The inflammatory cytokines TNF-alpha and IL-1 could be key components of the EC response, acting through regulation of VWF mobilization to the cell surface. Thrombus formation was then initiated by the binding of platelet GPIbalpha to endothelial VWF in our model, and this effect was inhibited by the ROS scavenger N-acetylcysteine. Actin linker talin-dependent activation of alphaIIb-beta3 integrin or Rac1 in platelets was required for late-phase thrombus stability. Our novel imaging technology illustrates the molecular mechanism underlying inflammation-based thrombus formation by discoid platelets on undisrupted ECs and suggests control of ROS could be a useful therapeutic target for the prevention of thrombotic diseases. PMID- 22096247 TI - Integrin-alphavbeta3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells. AB - Throughout life, one's blood supply depends on sustained division of hematopoietic stem cells (HSCs) for self-renewal and differentiation. Within the bone marrow microenvironment, an adhesion-dependent or -independent niche system regulates HSC function. Here we show that a novel adhesion-dependent mechanism via integrin-beta3 signaling contributes to HSC maintenance. Specific ligation of beta3-integrin on HSCs using an antibody or extracellular matrix protein prevented loss of long-term repopulating (LTR) activity during ex vivo culture. The actions required activation of alphavbeta3-integrin "inside-out" signaling, which is dependent on thrombopoietin (TPO), an essential cytokine for activation of dormant HSCs. Subsequent "outside-in" signaling via phosphorylation of Tyr747 in the beta3-subunit cytoplasmic domain was indispensable for TPO-dependent, but not stem cell factor-dependent, LTR activity in HSCs in vivo. This was accompanied with enhanced expression of Vps72, Mll1, and Runx1, 3 factors known to be critical for maintaining HSC activity. Thus, our findings demonstrate a mechanistic link between beta3-integrin and TPO in HSCs, which may contribute to maintenance of LTR activity in vivo as well as during ex vivo culture. PMID- 22096248 TI - The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor alpha signaling. AB - Plasmacytoid dendritic cells (pDCs) produce large amounts of type I interferons (IFN-alpha/beta) in response to viral or endogenous nucleic acids through activation of their endosomal Toll-like receptors (TLR-7 and TLR-9). Enhanced TLR 7-mediated IFN-alpha production by pDCs in women, compared with men, has been reported, but whether sex hormones, such as estrogens, are involved in this sex based difference is unknown. Here we show, in humanized mice, that the TLR-7 mediated response of human pDCs is increased in female host mice relative to male. In a clinical trial, we establish that treatment of postmenopausal women with 17beta-estradiol markedly enhances TLR-7- and TLR-9-dependent production of IFN-alpha by pDCs stimulated by synthetic ligands or by nucleic acid-containing immune complexes. In mice, we found exogenous and endogenous estrogens to promote the TLR-mediated cytokine secretion by pDCs through hematopoietic expression of estrogen receptor (ER) alpha. Genetic ablation of ERalpha gene in the DC lineage abrogated the enhancing effect of 17beta-estradiol on their TLR-mediated production of IFN-alpha, showing that estrogens directly target pDCs in vivo. Our results uncover a previously unappreciated role for estrogens in regulating the innate functions of pDCs, which may account for sex-based differences in autoimmune and infectious diseases. PMID- 22096250 TI - Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. AB - We aimed to determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK(+) patients after allogeneic HSCT. Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK MK(+). MK(+) patients were significantly older (P = .0001), had lower white blood counts (P = .0006), and lower percentages of BM blasts (P = .0004); MK was associated with the presence of -5/5q-, -7, 7q-, abnl(12p), abnl(17p), -18/18q-, 20/20q-, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)-related cytogenetic abnormalities (P < .0001, each); and NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P < .0001), and tyrosine kinase domain mutations (P = .02) were less frequent in MK(+). Response to induction therapy and overall survival in MK(+) patients were dismal with a complete remission rate of 32.5% and a 4-year survival of 9%. MK retained its prognostic impact in AML with CK, AML with MDS-related cytogenetic abnormalities, and in a revised definition (MK R) excluding cases with recurrent genetic abnormalities according to WHO classification and those with derivative chromosomes not leading to true monosomies. In younger patients, allogeneic HSCT from matched related and unrelated donors resulted in a limited improvement of overall survival. PMID- 22096249 TI - Histone deacetylases mediate the silencing of miR-15a, miR-16, and miR-29b in chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) demonstrates a global down-regulation of miR 15a and miR-16 and a selective silencing of the related miR-29b in aggressive disease. Deletions in chromosome 13 [del(13q14)] partially account for the loss of expression of miR-15a and miR-16, but the mechanisms by which miR-29b becomes silenced is unknown. In the present study, we show that the histone deacetylases (HDACs) are overexpressed in CLL and mediate the epigenetic silencing of miR-15a, miR-16, and miR-29b. HDAC inhibition triggered the accumulation of the transcriptionally activating chromatin modification H3K4me2 and restored the expression of miR-15a, miR-16, and miR-29b in approximately 35% of samples. Ectopic expression of miR-15a and miR-16 and HDAC inhibition-induced expression of miR-15a, miR-16, or miR-29b in primary CLL cells was associated with declines in the levels of Mcl-1, but not Bcl-2, mitochondrial dysfunction, and induction of cell death. Therefore, our results show that HDACs aberrantly silence the expression of the critical tumor suppressors miR-15a, miR-16, and miR-29b in CLL. Deacetylase inhibition may be a therapeutic strategy that restores the expression of these miRs to antagonize Mcl-1, an important survival protein in these cells. Consequently, CLL patients who exhibit such epigenetic silencing may benefit from HDAC inhibitor-based therapy. PMID- 22096251 TI - ARHGAP25, a novel Rac GTPase-activating protein, regulates phagocytosis in human neutrophilic granulocytes. AB - Members of the Rac/Rho family of small GTPases play an essential role in phagocytic cells in organization of the actin cytoskeleton and production of toxic oxygen compounds. GTPase-activating proteins (GAPs) decrease the amount of the GTP-bound active form of small GTPases, and contribute to the control of biologic signals. The number of potential Rac/RhoGAPs largely exceeds the number of Rac/Rho GTPases and the expression profile, and their specific role in different cell types is largely unknown. In this study, we report for the first time the properties of full-length ARHGAP25 protein, and show that it is specifically expressed in hematopoietic cells, and acts as a RacGAP both in vitro and in vivo. By silencing and overexpressing the protein in neutrophil model cell lines (PLB-985 and CosPhoxFcgammaR, respectively) and in primary macrophages, we demonstrate that ARHGAP25 is a negative regulator of phagocytosis acting probably via modulation of the actin cytoskeleton. PMID- 22096253 TI - The kiss of death in FL. AB - In this issue of Blood, Laurent et al use 3-D confocal imaging to visualize CD8+ T-cell lytic immune synapses in follicular lymphoma and report that this activity may influence progression-free survival after rituximab-chemotherapy. PMID- 22096252 TI - The adaptor protein Shc integrates growth factor and ECM signaling during postnatal angiogenesis. AB - Angiogenesis requires integration of cues from growth factors, extracellular matrix (ECM) proteins, and their receptors in endothelial cells. In the present study, we show that the adaptor protein Shc is required for angiogenesis in zebrafish, mice, and cell-culture models. Shc knockdown zebrafish embryos show defects in intersegmental vessel sprouting in the trunk. Shc flox/flox; Tie2-Cre mice display reduced angiogenesis in the retinal neovascularization model and in response to VEGF in the Matrigel plug assay in vivo. Functional studies reveal a model in which Shc is required for integrin-mediated spreading and migration specifically on fibronectin, as well as endothelial cell survival in response to VEGF. Mechanistically, Shc is required for activation of the Akt pathway downstream of both integrin and VEGF signaling, as well as for integration of signals from these 2 receptors when cells are grown on fibronectin. Therefore, we have identified a unique mechanism in which signals from 2 critical angiogenic signaling axes, integrins and VEGFR-2, converge at Shc to regulate postnatal angiogenesis. PMID- 22096254 TI - Gene mutation and AML pathogenesis. AB - In their large study of 1185 patients with acute myeloid leukemia (AML), Shen and colleagues have dissected the overlapping incidences and prognostic significances of mutations of the 12 genes most frequently mutated in AML,including FLT3, NPM1, CEBPA, KIT, N-RAS, MLL, WT1, IDH1/2, TET2, DNMT3A, and ASXL1. PMID- 22096255 TI - Angiogenesis: the HETE is on. AB - In this issue of Blood, Singh and colleagues identify HMG-CoA reductase-dependent farnesylation of Rac-1 as critical for 15(S)-HETE-induced angiogenesis. These findings establish a novel link between eicosanoid and cholesterol metabolism with important biologic and therapeutic implications for angiogenesis. PMID- 22096256 TI - How evidence based is English public health policy? PMID- 22096257 TI - Buffer Standards for the Biological pH of the Amino Acid N-[2 hydroxyethyl]piperazine-N'-[3-propanesulfonic acid], HEPPS, From (278.15 to 328.15) K. AB - For the HEPPS buffer under investigation, there are seven buffer solutions without NaCl and eight buffer solutions that contain Cl(-) and have an ionic strength (I = 0.16 mol.kg(-1)), which is similar to that of blood plasma. These buffer solutions have been evaluated in the temperature range of (278.15 to 328.15) K using the extended Debye- Huckel equation and the Bates-Guggenheim convention. The previously determined E(j) values have been used to determine the operational pH values of HEPPS buffer solutions at (298.15 and 310.15) K. These are recommended as secondary standard reference solutions for pH measurements in saline media with an isotonic ionic strength of I = 0.16 mol.kg(-1). PMID- 22096258 TI - Low power, biologically benign NIR light triggers polymer disassembly. AB - Near infrared (NIR) irradiation can penetrate up to 10 cm deep into tissues and be remotely applied with high spatial and temporal precision. Despite its potential for various medical and biological applications, there is a dearth of biomaterials that are responsive at this wavelength region. Herein we report a polymeric material that is able to disassemble in response to biologically benign levels of NIR irradiation upon two-photon absorption. The design relies on the photolysis of the multiple pendant 4-bromo7-hydroxycoumarin protecting groups to trigger a cascade of cyclization and rearrangement reactions leading to the degradation of the polymer backbone. The new material undergoes a 50% Mw loss after 25 sec of ultraviolet (UV) irradiation by single photon absorption and 21 min of NIR irradiation via two-photon absorption. Most importantly, even NIR irradiation at biologically benign laser power is sufficient to cause significant polymer disassembly. Furthermore, this material is well tolerated by cells both before and after degradation. These results demonstrate for the first time a NIR sensitive material with potential to be used for in vivo applications. PMID- 22096259 TI - Open Wound Healing In Vivo: Monitoring Binding and Presence of Adhesion/Growth Regulatory Galectins in Rat Skin during the Course of Complete Re Epithelialization. AB - Galectins are a family of carbohydrate-binding proteins that modulate inflammation and immunity. This functional versatility prompted us to perform a histochemical study of their occurrence during wound healing using rat skin as an in vivo model. Wound healing is a dynamic process that exhibits three basic phases: inflammation, proliferation, and maturation. In this study antibodies against keratins-10 and -14, wide-spectrum cytokeratin, vimentin, and fibronectin, and non-cross-reactive antibodies to galectins-1, -2, and -3 were applied to frozen sections of skin specimens two days (inflammatory phase), seven days (proliferation phase), and twenty-one days (maturation phase) after wounding. The presence of binding sites for galectins-1, -2, -3, and -7 as a measure for assessing changes in reactivity was determined using labeled proteins as probes. Our study detected a series of alterations in galectin parameters during the different phases of wound healing. Presence of galectin-1, for example, increased during the early phase of healing, whereas galectin-3 rapidly decreased in newly formed granulation tissue. In addition, nuclear reactivity of epidermal cells for galectin-2 occurred seven days post-trauma. The dynamic regulation of galectins during re-epithelialization intimates a role of these proteins in skin wound healing, most notably for galectin-1 increasing during the early phases and galectin-3 then slightly increasing during later phases of healing. Such changes may identify a potential target for the development of novel drugs to aid in wound repair and patients' care. PMID- 22096260 TI - Immunohistochemical and Immunocytochemical Localization of Amylase in Rat Parotid Glands and von Ebner's Glands by Ion Etching-Immunoscanning Electron Microscopy. AB - The distribution of amylase in rat parotid glands and von Ebner's glands was examined using ion etching-immunoscanning electron microscopy, which enables both light and electron microscopic observations of identical semi-thin resin sections immunolabeled with anti-alpha-amylase and immunogold in association with silver enhancement. At the light microscopic level, most acinar secretory granules (SG) and striated duct secretions of parotid glands were strongly stained dark brown. In von Ebner's glands, acinar SG and duct secretions were weakly to strongly stained light to dark brown. At the electron microscopic level, labeling was observed as bright gold-silver particles. The labeling intensity of acinar SG of parotid glands was higher than that of von Ebner's glands. In parotid glands, weak labeling of SG in transitional cells between acini and intercalated ducts, very weak labeling of SG in intercalated ducts, and strong labeling of striated duct secretions were observed. In von Ebner's glands, the secretions and some SG of interlobular ducts were strongly labeled compared to those of intralobular ducts and SG of acini. Less amylase was synthesized in von Ebner's acini compared to parotid acini, whereas von Ebner's ducts may secrete significantly more amylase to modify saliva than parotid ducts. PMID- 22096261 TI - Transplantation of bone marrow-derived mesenchymal stem cells into the developing mouse eye. AB - Mesenchymal stem cells (MSCs) have been studied widely for their potential to differentiate into various lineage cells including neural cells in vitro and in vivo. To investigate the influence of the developing host environment on the integration and morphological and molecular differentiation of MSCs, human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transplanted into the developing mouse retina. Enhanced green fluorescent protein (GFP)-expressing BM MSCs were transplanted by intraocular injections into mice, ranging in ages from 1 day postnatal (PN) to 10 days PN. The survival dates ranged from 7 days post transplantation (DPT) to 28DPT, at which time an immunohistochemical analysis was performed on the eyes. The transplanted BM-MSCs survived and showed morphological differentiation into neural cells and some processes within the host retina. Some transplanted cells expressed microtubule associated protein 2 (MAP2ab, marker for mature neural cells) or glial fibrillary acid protein (GFAP, marker for glial cells) at 5PN 7DPT. In addition, some transplanted cells integrated into the developing retina. The morphological and molecular differentiation and integration within the 5PN 7DPT eye was greater than those of other-aged host eye. The present findings suggest that the age of the host environment can strongly influence the differentiation and integration of BM-MSCs. PMID- 22096262 TI - Autophagy is constitutively active in normal mouse sino-atrial nodal cells. AB - This study was designed to examine the autophagy in sino-atrial (SA) nodal cells from the normal adult mouse heart. Autophagy is the cellular process responsible for the degradation and recycling of long-lived and/or damaged cytoplasmic components by lysosomal digestion. In the heart, autophagy is known to occur at a low level under physiological conditions, but to become upregulated when cells are exposed to certain stresses, such as ischemia. We examined whether the basal level of autophagy in SA nodal cells was different from that in ventricular or atrial myocytes. An ultrastructural analysis revealed that the SA nodal cells contained a number of autophagic vacuoles (autophagosomes) with various stages of degradation by lysosomal digestion, whereas the number of those in ventricular or atrial myocytes was either negligible or very small. The immunostaining of autophagosome marker microtubule-associated protein 1 light chain 3 (LC3) and lysosome marker lysosome-associated membrane protein 1 (LAMP1) indicated that the content of both autophagosomes and lysosomes were much greater in SA nodal cells than in ordinary cardiomyocytes. Our results provide evidence that the autophagy is active in normal SA nodal cells, which is not a stress-activated process but a constitutive event in the mouse heart. PMID- 22096263 TI - Replication Banding Patterns in Human Chromosomes Detected Using 5-ethynyl-2' deoxyuridine Incorporation. AB - A novel technique using the incorporation of 5-ethynyl-2'-deoxyuridine (EdU) into replicating DNA is described for the analysis of replicating banding patterns of human metaphase chromosomes. Human lymphocytes were synchronized with excess thymidine and treated with EdU during the late S phase of the cell cycle. The incorporated EdU was then detected in metaphase chromosomes using Alexa Fluor(r) 488 azides, through the 1,3-dipolar cycloaddition reaction of organic azides with the terminal acetylene group of EdU. Chromosomes with incorporated EdU showed a banding pattern similar to G-banding of normal human chromosomes. Imaging by atomic force microscopy (AFM) in liquid conditions showed that the structure of the chromosomes was well preserved even after EdU treatment. Comparison between fluorescence microscopy and AFM images of the same chromosome 1 indicated the presence of ridges and grooves in the chromatid arm, features that have been previously reported in relation to G-banding. These results suggest an intimate relationship between EdU-induced replication bands and G- or R-bands in human chromosomes. This technique is thus useful for analyzing the structure of chromosomes in relation to their banding patterns following DNA replication in the S phase. PMID- 22096264 TI - Experimental and theoretical advances in prosody: A review. AB - Research on prosody has recently become an important focus in various disciplines, including Linguistics, Psychology, and Computer Science. This article reviews recent research advances on two key issues: prosodic phrasing and prosodic prominence. Both aspects of prosody are influenced by linguistic factors such as syntactic constituent structure, semantic relations, phonological rhythm, pragmatic considerations, and also by processing factors such as the length, complexity or predictability of linguistic material. Our review summarizes recent insights into the production and perception of these two components of prosody and their grammatical underpinnings. While this review only covers a subset of a broader set of research topics on prosody in cognitive science, they are representative of a tendency in the field toward a more interdisciplinary approach. PMID- 22096265 TI - Accent detection is a slippery slope: Direction and rate of F0 change drives listeners' comprehension. AB - The present study tests whether listeners use F0, duration, or some combination of the two to identify the presence of an accented word in a short discourse. Participants' eye movements to previously mentioned and new objects were monitored as participants listened to instructions to move objects in a display. The name of the target object on critical trials was resynthesized from naturally produced utterances so that it had either high or low F0 and either long or short duration. Fixations to the new object were highest when there was a steep rise in F0. Fixations to the previously mentioned object were highest when there was a steep drop in F0. These results suggest that listeners use F0 slope to make decisions about the presence of an accent, and that F0 and duration by themselves do not solely determine accent interpretation. PMID- 22096266 TI - Distributed impact of cognitive-communication impairment: Disruptions in the use of definite references when speaking to individuals with amnesia. AB - BACKGROUND: Definite references signal a speaker's belief that a listener can uniquely identify the referent (e.g., the dog, as the only dog among a group of animals). Clark's (1992) collaborative referencing model provides a way to examine the speaker's display of confidence that his/her reference will be understood by the listener without further clarification. We previously found that amnesia participants, as directors in a barrier task with a familiar partner, used referencing forms that displayed less confidence than forms used by comparison participants. If this is an interactional consequence of managing the memory impairment (as opposed to a language deficit), we should also expect a decrease in definite referencing by their partners. AIMS: To examine the use of definite references by healthy non-brain-damaged participants when speaking to their memory-impaired partner during repeated trials of a barrier task. METHODS #ENTITYSTARTX00026; PROCEDURES: We replicated our previous work with 11 of the same participant pairs-6 individuals with hippocampal amnesia and 5 comparison participants-each of whom was paired with a familiar partner of their choosing. Focusing on the productions of the partners (i.e., partners became directors) we (1) coded referential expressions as definite or indefinite; (2) tracked changes in the use of indefinite and definite references across trials; and (3) compared data to previous analyses (when amnesia participants were directors). OUTCOMES #ENTITYSTARTX00026; RESULTS: The productions of comparison pairs were overwhelming definite (95%, 1359). In sharp contrast, partners of the amnesia participants used a definite initiating reference less than half the time (48%, 825), when speaking to their memory-impaired partner and used definite references that signalled a lack of confidence more often and across more trials. CONCLUSIONS: These findings support the assumption that disruptions in language and-memory-in-use are not limited to the productions of the individuals with amnesia, but rather extend to the discourse of their communication partners. Observing disruptions in the use of definite references of individuals with intact language and declarative memory, when communicating with their partner with amnesia, points to the complex interaction of memory and language. Even when attention is paid to grammatical forms, the decisions are never linguistic alone. PMID- 22096267 TI - Shyness and Vocabulary: The Roles of Executive Functioning and Home Environmental Stimulation. AB - Although shyness has often been found to be negatively related to vocabulary, few studies have examined the processes that produce or modify this relation. The present study examined executive functioning skills and home environmental stimulation as potential mediating and moderating mechanisms. A sample of 3.5 year-old children (N=254) were administered executive functioning tasks and a vocabulary test during a laboratory visit. Mothers completed questionnaires assessing child shyness and home environmental stimulation. Our primary hypothesis was that executive functioning mediates the association between shyness and vocabulary, and home environmental stimulation moderates the relation between executive functioning and vocabulary. Alternative hypotheses were also tested. Results indicated that children with better executive functioning skills developed stronger vocabularies when reared in more, versus less, stimulating environments. Implications of these results are discussed in terms of the role of shyness, executive functioning, and home environmental stimulation in early vocabulary development. PMID- 22096268 TI - Dual Processes in Decision Making and Developmental Neuroscience: A Fuzzy-Trace Model. AB - From Piaget to the present, traditional and dual-process theories have predicted improvement in reasoning from childhood to adulthood, and improvement has been observed. However, developmental reversals-that reasoning biases emerge with development -have also been observed in a growing list of paradigms. We explain how fuzzy-trace theory predicts both improvement and developmental reversals in reasoning and decision making. Drawing on research on logical and quantitative reasoning, as well as on risky decision making in the laboratory and in life, we illustrate how the same small set of theoretical principles apply to typical neurodevelopment, encompassing childhood, adolescence, and adulthood, and to neurological conditions such as autism and Alzheimer's disease. For example, framing effects-that risk preferences shift when the same decisions are phrases in terms of gains versus losses-emerge in early adolescence as gist-based intuition develops. In autistic individuals, who rely less on gist-based intuition and more on verbatim-based analysis, framing biases are attenuated (i.e., they outperform typically developing control subjects). In adults, simple manipulations based on fuzzy-trace theory can make framing effects appear and disappear depending on whether gist-based intuition or verbatim-based analysis is induced. These theoretical principles are summarized and integrated in a new mathematical model that specifies how dual modes of reasoning combine to produce predictable variability in performance. In particular, we show how the most popular and extensively studied model of decision making-prospect theory-can be derived from fuzzy-trace theory by combining analytical (verbatim-based) and intuitive (gist-based) processes. PMID- 22096269 TI - Bis(1,2,3-triazol-5-ylidenes) (i-bitz) as Stable 1,4-Bidentate Ligands Based on Mesoionic Carbenes (MICs). AB - Direct metalation of bis(1,2,3-triazolium) salts affords mononuclear rhodium(I) complexes, which feature a 1,4-bidentate bis(1,2,3-triazol-5-ylidene) (i-bitz) ligand. The topology of the ligand is similar to 2,2'-bipyridines (bpy) and their congeners, as well as bis(1,2,4-triazol-5-ylidenes) (bitz). As the former, but in contrast to the latter, the free i-bitz can be isolated, which paves the way for various applications. PMID- 22096270 TI - Problem Drinking, Unemployment, and Intimate Partner Violence among a Sample of Construction Industry Workers and their Partners. AB - The purpose of this study is to determine the contribution of male unemployment and each partner's problem drinking to risk for male-to-female partner violence (MFPV) and female-to-male partner violence (FMPV) among a sample of construction industry workers and their spouses/partners. Participants in the sample (n=848 couples) completed cross-sectional health behavior surveys. Multivariate logistic regression models of MFPV and FMPV, with adjustment for demographic and psychosocial variables, were developed. Approximately 20% of couples reported MFPV, and 24% reported FMPV. Results indicated that couples in which the male was a problem drinker, and in which the male worker reported being currently unemployed, were at risk for MFPV. Number of months unemployed by the male worker was significantly associated with FMPV, but problem drinking was not associated with this outcome. Male and female impulsivity were significantly associated with risk for MFPV and FMPV, and the male's report of adverse childhood events was associated with increased likelihood of MFPV. There was no evidence for the effects of unemployment being moderated (exacerbated) by problem drinking. Workplace-based prevention efforts may be a feasible and important strategy to reduce problem drinking and partner violence among high-risk occupational groups. PMID- 22096271 TI - AUDIO-CASI: Hardware and Software Considerations in Adding Sound to a Computer Assisted Interviewing System. AB - This article reviews a multimedia application in the area of survey measurement research: adding audio capabilities to a computer-assisted interviewing system. Hardware and software issues are discussed, and potential hardware devices that operate from DOS platforms are reviewed. Three types of hardware devices are considered: PCMCIA devices, parallel port attachments, and laptops with built-in sound. PMID- 22096272 TI - Anesthesia : Contributing to pollution? PMID- 22096273 TI - Prevention of local anesthetic systemic toxicity. PMID- 22096274 TI - Psychiatric diseases: Need for an increased awareness among the anesthesiologists. AB - Psychological disorders and psychiatric diseases have been on the rise since the last three decades. An increasing number of such patients are encountered nowadays for elective or emergency surgery. A multi-array of challenges are faced while anesthetizing these patients or treating them in an intensive care unit. The problems include the deteriorated mental physiology, altered cognition and the possible drug interactions with psychotropic medications. The challenge starts from the preoperative assessment stage. Knowledge of the pharmacological profile of the various anti-psychotic drugs, their side-effects and drug interactions are of prime importance for an anesthesiologist to facilitate smooth delivery of anesthesia in such patients. It is important to formulate a clear plan to deal with any challenge in the perioperative or postoperative period. All the clinical aspects and various definitions of mental disorders in the present article have been used as per the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). We reviewed the advances in psychiatric diseases, their treatment and their implications on delivery of anesthesia. PMID- 22096275 TI - A systematic review of the effects of sedatives and anesthetics in patients with obstructive sleep apnea. AB - The objective of this review is to determine the effects of perioperative sedatives and anesthetics in surgical patients with obstructive sleep apnea (OSA) on respiratory events, medication requirements, hemodynamics, pain, emergence, and hospital stay. We searched The Cochrane CENTRAL Register of Controlled Trials, Medline, Embase, and Cochrane Database of Systematic Reviews from 1950 to June 2010 for relevant articles. All prospective and retrospective studies were eligible for inclusion if the effects of perioperative administration of sedation and anesthetics on medication requirements, pain, emergence, hemodynamics, respiratory events, and length of hospital stay in OSA patients were reported. The search strategy yielded 18 studies of 1467 patients. Of these, 456 patients were documented as having OSA. Few adverse respiratory effects were reported. Eight out of 700 (1.14%) patients undergoing middle ear surgery with midazolam and fentanyl had impaired upper airway patency and were retrospectively diagnosed as having OSA by polysomnography. Also, intraoperative snoring causing uvular edema in the postoperative period was described in an OSA patient undergoing upper limb surgery when propofol was administered with midazolam and fentanyl for sedation. A decrease in oxygen saturation in the postoperative period was described with propofol and isoflurane in 21 OSA patients undergoing uvulo-palato pharyngoplasty and tonsillectomy surgery (P<0.05). Perioperative alpha 2 agonists were shown to decrease the use of anesthetics (P<0.05), analgesics (P=0.008) and anti-hypertensives (P<0.001) in OSA patients. Contradictory reports regarding emergence occurred with intraoperative dexmedetomidine. Intraoperative opioids decreased the analgesic consumption (P=0.03) and pain scores (P<0.05) in the postoperative period. There was limited data on the length of hospital stay. There were few adverse effects reported when patients with known OSA underwent elective surgery with the currently available sedatives and anesthetics. Adverse events were reported with midazolam. However, the quality and number of patients in the studies were limited. There is a need for further trials with large numbers and uniform reporting of outcomes. PMID- 22096276 TI - Combined spinal epidural and epidural volume extension: Interaction of patient position and hyperbaric bupivacaine. AB - BACKGROUND: Previous trials have documented failure of block augmentation with epidural volume extension, when applied after the intrathecal injection of hyperbaric bupivacaine was made in sitting position. However, there is no study comparing the effect of change in patient position during block performance, on the results of epidural volume extension. MATERIALS AND METHODS: The study was conducted in two parts in American Society of Anesthesiologists physical status I or II parturients scheduled for elective cesarean section under regional anesthesia. In the first part, 28 patients were randomized to one of the two groups, depending on whether epidural volume extension was applied following the block in sitting (group SE) or lateral position (group LE) (n=14 each). In the second part of the study another 28 patients were recruited and randomized to receive the block in sitting (group S) or lateral (group L) position (n=14 each), without epidural volume extension. All patients received combined spinal epidural block using needle-through-needle technique with intrathecal injection of 9 mg hyperbaric bupivacaine (0.5%) and 10 MUg fentanyl. Epidural volume extension was performed using 5 ml normal saline in groups SE and LE. RESULTS: In the first part of the study, the maximum sensory block level was higher in group LE vs. SE (P<0.05). In the second part of the study, no significant difference was seen in the maximum sensory level between group S and group L (P>0.05). CONCLUSIONS: If epidural volume extension is being applied with intention of rapid extension of sensory block when hyperbaric bupivacaine has been injected intrathecally, the combined spinal epidural block should be performed in lateral position rather than in the sitting position. PMID- 22096277 TI - Bier's block using lignocaine and butorphanol. AB - BACKGROUND: Opioids are most commonly used as adjuncts in intravenous regional anesthesia (IVRA) to improve the quality of intraoperative and postoperative analgesia. There is paucity of literature on the use of butorphanol in IVRA. AIMS: The aim of this study was to evaluate the likely benefits of addition of butorphanol to lignocaine in Bier's block in terms of onset and duration of sensory block and also for analgesic requirement in postoperative period. SETTINGS AND DESIGN: A randomized double blind study was conducted at Tertiary Care Educational Institute. PATIENTS AND METHODS: A total of 40 adult ASA I or II patients scheduled to undergo upper limb surgery were randomized in two groups (n=20). Group I received 3 mg/kg of lignocaine alone and group II received 1 mg butorphanol in addition to 3 mg/kg lignocaine. Sensory block onset time and time to recovery from sensory block after tourniquet deflation were noted using the pin prick method. Duration of postoperative analgesia was noted using a visual analogue scale. All the patients were compared for the time to first rescue analgesic consumption and total analgesic consumption in first 24 hours postoperatively. STATISTICAL ANALYSIS USED: The statistical analysis was done using unpaired Student's t-test. RESULTS: Our study showed significant prolongation of postoperative analgesia in group II as noted by the time to first analgesic requirement. Total analgesic consumption in first 24 hours postoperatively was less in group II. Sensory block onset time and time to recovery from sensory block after tourniquet deflation, did not show any significant difference between the two groups. CONCLUSIONS: Addition of butorphanol to lignocaine in IVRA significantly prolongs the duration of postoperative analgesia and 24 hours analgesic consumption is less in patients receiving butorphanol along with lignocaine in IVRA. However, there is no effect on sensory block onset time and time to recovery from sensory block. PMID- 22096278 TI - Role of hydrocortisone in prevention of pain on propofol injection. AB - BACKGROUND AND OBJECTIVES: Pain following intravenous injection of propofol continues to be an intriguing problem. None of the commonly used methods completely attenuate the pain. Inflammatory response to propofol contributes to the pain. Role of hydrocortisone in attenuating pain has not been evaluated. This study was conducted to compare the efficacy of lignocaine and hydrocortisone in attenuation of pain following intravenous injection of propofol. MATERIALS AND METHODS: A prospective randomized double-blind, placebo-controlled study was conducted on 72 adult patients belonging to American Society of Anesthesiologists (ASA) physical status I or II, scheduled to undergo elective surgery. They were randomly assigned to four groups of 18 each. Group NS, group LG, group HC10, and group HC25. The groups received 2 ml normal saline, 2 ml 2% lignocaine, 10 mg/2 ml hydrocortisone, and 25 mg/2 ml hydrocortisone, respectively, as pretreatment. Propofol was injected 30 sec later. A blinded researcher assessed the patient's pain level using a four point verbal rating scale. RESULTS: The four groups were comparable in respect to patient's characteristics. There was no significant difference of hemodynamics changes during propofol induction between all the groups. There was no statistically significant difference in the incidence of pain between patients who received hydrocortisone and the placebo group. The incidence of pain was significantly less in group LG than other three groups. CONCLUSION: Use of intravenous low dose hydrocortisone pretreatment of the vein does not attenuate pain following propofol injection. PMID- 22096279 TI - Hemodynamic stress response during laparoscopic cholecystectomy: Effect of two different doses of intravenous clonidine premedication. AB - BACKGROUND: Clonidine has emerged as an attractive premedication desirable in laparoscopic surgery wherein significant hemodynamic stress response is seen. The minimum safe and effective dose of intravenous clonidine to attenuate the hemodynamic stress response during laparoscopic surgery has however not yet been determined. MATERIALS AND METHODS: This prospective, randomized, double-blind controlled study was conducted on 90 adults of ASA physical status I and II, scheduled for laparoscopic cholecystectomy under general anesthesia. Patients were randomized to one of the three groups (n= 30). Group I received 100 ml of normal saline, while groups II and III received 1 MUg/ kg and 2 MUg/ kg of clonidine respectively, intravenous, in 100 ml of normal saline along. All patients received glycopyrrolate 0.004 mg/kg and tramadol 1.5 mg/kg intravenously, 30 min before induction. Hemodynamic variables (heart rate, systolic, diastolic, mean arterial pressure), SpO2, and sedation score were recorded at specific timings. MAP above 20% from baseline was considered significant and treated with nitroglycerine. RESULTS: In group I, there was a significant increase in hemodynamic variables during intubation pneumoperitoneum and extubation (P<0.001). Clonidine given 1 MUg/kg intravenous attenuated hemodynamic stress response to pneumoperitoneum (P<0.05), but not that associated with intubation and extubation. Clonidine 2 MUg/kg intravenous prevented hemodynamic stress response to pneumoperitoneum and that associated with intubation and extubation (P<0.05). As against 14 and 2 patients in groups I and II respectively, no patient required nitroglycerine infusion in group III. CONCLUSIONS: Clonidine, 2 MUg/ kg intravenously, 30 min before induction is safe and effective in preventing the hemodynamic stress response during laparoscopic cholecystectomy. PMID- 22096280 TI - The analgesic efficacy of peritubal infiltration of 0.25% bupivacaine in percutaneous nephrolithotomy - A prospective randomized study. AB - BACKGROUND: Percutaneous nephrolithotomy is a routine endourologic procedure in patients with renal stones. Although it is less painful than open surgery, good postoperative analgesia is required to alleviate pain around nephrostomy tube. MATERIALS AND METHODS: Sixty ASA grade I patients, 18 to 60 years of age, of either sex were randomized to receive 20 ml of 0.25% bupivacaine (group S) or 20 ml of normal saline (group C) through 23-gauge spinal needle along the nephrostomy tube under fluroscopic guidance at the end of the surgery. Postoperative pain score was assessed by visual and dynamic visual analog scores. When the scores were >=4, rescue analgesia was given in the form of tramadol 1 mg/kg i.v. upto maximum 400 mg in 24 hours. Time to first demand analgesia and total dose of tramadol in first 24 hours was noted. RESULTS: Pain scores at rest and during coughing as well as rescue analgesic requirements for first 24 hours were significantly less in the bupivacaine group than those of the control group (P < 0.05). The first request for demand analgesia was around 9 hours in group S, while in group C it was around 2.6 hours (P < 0.05). Total requirement of tramadol in group S was 119.3 mg and in C group it was 276.8 mg (P < 0.05). CONCLUSION: Peritubal infiltration of 0.25% bupivacaine is efficient in alleviating postoperative pain after PCNL. PMID- 22096281 TI - Preventive analgesia: Effect of small dose of ketamine on morphine requirement after renal surgery. AB - BACKGROUND: N-methyl D-Aspartate (NMDA) receptors seem to be responsible for pain memory and their blockade can contribute significantly in prevention of pain. This study was conducted to evaluate the preventive effect of small dose of ketamine, a NMDA receptor blocker, given before skin incision in renal surgery, with the aim to compare analgesic efficacy, intra operative and post-operative side effects. MATERIALS AND METHODS: In a prospective double-blind study, 60 American Society of Anesthesiologists (ASA) risk I and II adult patients scheduled for elective open renal surgeries by flank incision were randomly divided in two groups. Ketamine group (group K) received ketamine 0.15 mg/kg intravenously, 30 minute before start of surgery followed by infusion of ketamine 2 mcg/kg/min till start of skin closure. Control group (group C) received normal saline in place of ketamine. Both groups received morphine 0.15 mg/ kg i.v. at the time of skin closure. The analgesic efficacy was judged by visual analogue scale (VAS) at rest and on movement, time to first analgesic and morphine consumption in 24 hours. Opioid or ketamine related side effects were also recorded. RESULTS: Patients in ketamine group had significantly lower VAS score, longer time to first analgesic (21.6 +/- 0.12 Vs 3.8 +/- 0.7 hrs), and lower morphine consumption (5.8 +/- 1.48 Vs 18.1 +/- 1.6 mg) in 24 hours. There were no demonstrable side effects related to ketamine in group K whereas incidence of nausea and vomiting was higher in group C. CONCLUSION: Our results demonstrate that small dose of ketamine decreases post-operative pain, reduces morphine consumption, and delays patients request for analgesia beyond the clinical duration of action of ketamine after open renal surgery. PMID- 22096282 TI - Pre-emptive oral dexmethorphan reduces fentanyl-induced cough as well as immediate postoperative adrenocortico-tropic hormone and growth hormone level. AB - BACKGROUND: Fentanyl-induced cough is not always benign and brief and can be remarkably troublesome, spasmodic, and explosive. Dextromethorphan, an opioid derivative with an antitussive action, may be effective in reducing the fentanyl induced cough. Dextromethorphan, a N-methyl D aspartate receptor antagonist, may have some effect on diminishing the stress response to surgery. This study was undertaken to determine whether preoperative dextromethorphan could effectively attenuate its incidence, severity, and effect on postoperative stress hormone levels. MATERIALS AND METHODS: Three hundred and twenty patients of American society of anesthesiologists I-II, aged 18-60 years, undergoing elective laparoscopic cholecystectomy or appendicectomy were randomly allocated into two groups (Group C, control; Group D, dextromethorphan) consisting of 160 patients each. Patients in Group D received dextromethorphan 40 mg orally and in Group C received placebo tablets 60 minutes before induction of anesthesia. The incidence of cough was recorded for 1 minute after fentanyl injection and graded as none (0), mild (1-2), moderate (3-5), and severe (>5 cough). Blood samples were collected for estimation of stress hormone levels before surgery and again at 1 hour and 24 hours postoperatively and compared. The appearance of adverse reactions was recorded. RESULTS: The incidence of reflex fentanyl cough was lower in dextromethorphan group (3.9%) in comparison to placebo (59.8%). Five patients developed mild and one moderate cough in the dextromethorphan group. In the control group, 31 patients developed mild, 29 moderate, and 32 severe cough. The stress hormones were significantly higher at 1 hour and 24 hours postoperatively in both groups in comparison to its preoperative values. However, at 1 hour postoperatively, adrenocorticotropic hormone, epinephrine, and growth hormone values were significantly low in the dextromethorphan group (61.5 +/- 21.1 pg/ ml, 142.1 +/- 11.2 pg/ml, and 3.8 +/- 0.7 ng/ml) relative to the control group (73.4 +/- 21.9 pg/ml, 158.9 +/- 17.9 pg/ml, and 4.2 +/- 1.3 ng/ml), but changes became insignificant at 24 hours postoperatively. CONCLUSION: Preoperative oral dextromethorphan 40 mg decreased the incidence and severity of fentanyl induced cough and reduced the rise in stress hormones at 1 hour postoperatively. PMID- 22096283 TI - Comparative study of intrathecal dexmedetomidine with intrathecal magnesium sulfate used as adjuvants to bupivacaine. AB - BACKGROUND: No drug, used as adjuvant to spinal bupivacaine, has yet been identified that specifically inhibits nociception without its associated side effects. AIMS: This prospective randomized double-blind study was conducted to evaluate the onset and duration of sensory and motor block as well as perioperative analgesia and adverse effects of dexmedetomidine and magnesium sulfate given intrathecally with 0.5% hyperbaric bupivacaine for spinal anesthesia. MATERIALS AND METHODS: A total of 90 patients classified as American Society of Anesthesiologists status I and II scheduled for lower abdominal and lower limb procedures were prospectively studied. Patients were randomly allocated to receive intrathecally either 15 mg hyperbaric bupivacaine plus 0.1 ml (10 MUg) dexmedetomidine (group D, n=30) or 15 mg hyperbaric bupivacaine plus 0.1 ml (50 mg) magnesium sulfate (group M, n=30) or 15 mg hyperbaric bupivacaine plus 0.1 ml saline (group C, n=30) as control. The onset time to reach peak sensory and motor level, the regression time for sensory and motor block, hemodynamic changes and side-effects were recorded. STATISTICAL ANALYSIS USED: All statistical analyses were performed using INSTAT for windows. Continuous variables were tested for normal distribution by the Kolmogorov-Smirnov test. Data was expressed as either mean and standard deviation or numbers and percentages. Continuous covariates (age, body mass index and height) were compared using analysis of variance (ANOVA). For the times to reach T10 dermatomes, Bromage 3 scale and the regression of the sensory block to S1 dermatome and Bromage scale 0, one-way ANOVA was used to compare the means. The level of significance used was P<0.05. RESULTS: The onset times to reach T10 dermatome and to reach peak sensory level as well as onset time to reach modified Bromage 3 motor block were significantly different in the three groups. The onset time to reach peak sensory and motor level was shorter in group D as compared with the control group C, and it was significantly prolonged in group M. We also found that patients in group D had significant longer sensory and motor block times than patients in group M, which was greater than in the control group C. CONCLUSION: It was found that onset of anesthesia was rapid and of prolonged duration in the dexmedetomidine group (D). However, in the magnesium sulfate group (M), although onset of block was delayed, the duration was significantly prolonged as compared with the control group (C), but to a lesser degree than in the dexmedetomidine group (D). The groups were similar with respect to hemodynamic variables and there were no significant side-effects in either of the groups. PMID- 22096284 TI - Effect of intraoperative depth of anesthesia on postoperative pain and analgesic requirement: A randomized prospective observer blinded study. AB - BACKGROUND: Intraoperative depth of anesthesia may affect postoperative pain relief. This prospective, randomized, and observer-blinded study assessed the effect of intraoperative depth of anesthesia on the postoperative pain and analgesic requirements in patients undergoing laparoscopic cholecystectomy. MATERIALS AND METHODS: A total of 80 patients were randomly divided into two groups of 40 each. A standard technique for anesthesia was followed in all patients. Depth of anesthesia was monitored by bispectral index (BIS) and adjusted with 0.5 to 1.5% isoflurane in group S by addition of propofol in group B, if required, to maintain a BIS value of 45 to 40. Postoperative analgesia was provided by tramadol 1 mg/kg every 6 hours and rescue analgesia by morphine boluses. Postoperative pain was assessed by Visual analogue scale score at 0, 8, 16, and 24 hours. RESULTS: The demographic characteristics were comparable in both groups. The mean BIS value in Group S was 63.32 +/- 11.43 and 45.06 +/- 15.31 in Group B, well in the range of 40 to 60, reflecting adequate hypnotic effect for general anesthesia. The mean arterial pressure was low in group B throughout the surgery (P<0.05-0.001). The pain score were lower in group B at 0 and 8 hours postoperatively when compared with group S (P<0.05). The rescue analgesic requirement was less in group B, compared with group S (P<0.05). CONCLUSION: Maintaining BIS to a value of 45 to 40 throughout the surgery results in better postoperative pain relief and decreased requirement of rescue analgesic without any untoward effect. PMID- 22096285 TI - Student assessment of teaching effectiveness of "bundle of changes"-A paired, controlled trial. AB - BACKGROUND: Inching toward optimum patient safety by training personnel is the prime aim of the ongoing medical education. AIMS: To assess whether lectures targeted to improve quality care in ICU could improve ICU practitioners' knowledge levels and to evaluate the effectiveness of teaching. SETTINGS AND DESIGN: In this paired controlled trial, 50 ICU practitioners, i.e., anesthesia and medicine residents and nursing staff of our hospital attended a series of four lectures. MATERIALS AND METHODS: Participants enrolled in the study attended lectures on bundles of changes in ICU, namely, introduction, ventilator bundle, central line bundle, and catheter-related blood stream infections and severe sepsis bundle. They were given a questionnaire of 15 multiple choice questions prior to and after the lectures. We evaluated their immediate knowledge acquisition and retention recall. Subsequently, they evaluated the effectiveness of the teaching programme by a questionnaire of 10 multiple choice questions. STATISTICAL ANALYSIS USED: Data for statistical analysis were tabulated and analyzed using SPSS-Pc 11.5 version software. RESULTS: Fifty study participants completed all three questionnaires. There was an increase in the overall mean score in the post-lecture test (4.58 + 1.51 SD) (P < 0.001). Overall mean score increased significantly from 8.30 + 1.34 SD in THE pre-lecture test - to 12.02 + 1.61 SD in the postlecture re-test (3.72 + 1.39 SD) (P < 0.001). In the evaluation of teaching effectiveness 88% respondents agreed to most of the questions, signifying the effectiveness of the lectures. However, there were 10% who disagreed to the questions and only 2% strongly disagreed to all the questions. CONCLUSIONS: Teaching programmes such as the "bundle of changes" are effective in improving immediate knowledge acquisition and retention recall of the participants if designed keeping the target audience in mind. PMID- 22096286 TI - Patient's experiences and satisfaction with preanesthesia services: A prospective audit. AB - BACKGROUND: Patient satisfaction with the medical services is an important indicator of quality of healthcare but is seldom given importance in our country. It is difficult to measure patient satisfaction, especially in pre- and perioperative period. MATERIALS AND METHODS: We conducted this audit by means of a questionnaire designed to assess preanesthetic clinic services in a large government hospital. A total of 200 patients were randomly selected to respond to a multiple item questionnaire. STATISTICAL ANALYSIS: A database was created and analyzed using Microsoft Excel. RESULTS: 95% patients filled the proforma. Most of the patients (60%) were not aware of the purpose of visit to preanesthetic clinic. Majority of them were attended in time by the doctors but most of them (60%) received fitness after 2 to 3 visits. Majority was not explained about the preanesthesia instructions. Most of them were not satisfied by amenities in hospital. Several studies have shown that a thorough preoperative examination can be as effective as an anxiolytic premedication and can increase quality of care. In our study, location of preanesthetic clinic and unable to get fitness in first visit (because of lack of coordination between doctors of various specialties) were the major hindrances. CONCLUSION: Measures should be taken to improve the functioning of preanesthesia clinic and patient satisfaction. PMID- 22096288 TI - Effect of one minimum alveolar concentration sevoflurane with and without fentanyl on hemodynamic response to laryngoscopy and tracheal intubation. AB - BACKGROUND: Drug combinations can be used for optimum obtundation of the hemodynamic response to tracheal intubation. The objective of this trial was to compare the hemodynamic response to laryngoscopy and tracheal intubation after administration of 2 MUg/kg fentanyl bolus or a placebo with 2% end tidal sevoflurane at induction of anesthesia. MATERIALS AND METHODS: A total of 70 surgical patients of either gender, age 18-45 years were selected for this double blind, randomized, placebo controlled trial, with 35 in each group. All patients received a standardized induction with thiopentone, atracurium, and an end tidal concentration of 1 minimum alveolar concentration (MAC) sevoflurane. Heart rate and noninvasive blood pressure were compared to the baseline post induction and for seven minutes post intubation. Some adverse events were noted. RESULTS: The maximum heart rate response was significantly less in the sevoflurane fentanyl group (15% vs. 22%). Significant difference between groups was observed in the systolic blood pressure at six minutes post intubation. Hemodynamic adverse events recorded were similar. CONCLUSION: Addition of 2 MUg fentanyl bolus to 1 MAC sevoflurane anesthesia at induction attenuated the hemodynamic response to a maximum of 15% above baseline values. PMID- 22096287 TI - Stellate ganglion block for treatment of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage - A preliminary study. AB - BACKGROUND: Stellate ganglion block improves cerebral perfusion by decreasing the cerebral vascular tone. Its effects on cerebral vasospasm to relieve neurological deficits have not been evaluated. This prospective observational study was carried out to evaluate the effect of stellate ganglion block on cerebral hemodynamics in patients with symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage. MATERIALS AND METHODS: Fifteen patients of either sex, aged 18-75 years, who underwent surgical clipping of aneurysm and developed refractory cerebral vasospasm were included. Stellate ganglion block was performed using 10 ml of bupivacaine 0.5% on the side with maximum cerebral blood flow velocity. Neurological status, cerebral blood flow velocity and pulsatility index were assessed before and 10 minutes, 30 minutes, 2 hours, 6 hours, 12 hours and 24 hours after stellate ganglion block. RESULTS: Improved Glasgow coma score was observed 30 minutes after stellate ganglion block. Neurological deficits reduced in 11 patients. Ipsilateral middle cerebral artery mean flow velocity decreased from 133.66 cm/sec before stellate ganglion block to 110.53 cm/sec at 6 hours (P<0.001) and 121.62 cm/sec at 24 hours (P<0.001) after stellate ganglion block. There was a decrease in ipsilateral anterior cerebral artery mean flow velocity after stellate ganglion block (P<0.001), which persisted for 12 hours. A decline in flow velocities was observed in contralateral middle cerebral artery (P=0.008) and anterior cerebral artery (P=0.041) for 12 hours. CONCLUSION: This study suggests stellate ganglion block to be an effective modality of treatment for refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage. PMID- 22096289 TI - Electromagnetic interference in a cardiac pacemaker during cauterization with the coagulating, not cutting mode. AB - Electromagnetic interference in pacemakers has almost always been reported in association with the cutting mode of monopolar electrocautery and rarely in association with the coagulation mode. We report a case of electrocautery-induced electromagnetic interference with a DDDR pacemaker (dual-chamber paced, dual chamber sensed, dual response to sensing, and rate modulated) in the coagulating and not cutting mode during a spine procedure. We also discuss the factors affecting intraoperative electromagnetic interference. A 74-year-old man experienced intraoperative electromagnetic interference that resulted in asystole caused by surgical electrocautery in the coagulation mode while the electrodispersive pad was placed at different locations and distances from the operating site (This electromagnetic interference did not occur during the use of the cutting mode). However, because of careful management, the outcome was favorable. Clinicians should be aware that the coagulation mode of electrocautery can cause electromagnetic interference and hemodynamic instability. Heightened vigilance and preparedness can ensure a favorable outcome. PMID- 22096290 TI - Therapeutic drug monitoring of vancomycin in an obese patient with renal insufficiency. AB - We report the pharmacokinetics of vancomycin in an obese patient with renal insufficiency using pharmacokinetic equations, and comparing them with actual levels. A 47-year-old man with morbid obesity had a complicated hospital course with acute renal failure. Due to sputum growth of coagulase-negative Staphylococcus aureus, vancomycin 1500 mg intravenously twice daily was given empirically. Peak and trough plasma concentrations were drawn at steady state. Based on levels, true pharmacokinetic parameters for the patient were calculated using equations. This revealed that calculating individual pharmacokinetic parameters using equations may be a valid tool for dosing vancomycin in obese patients with renal insufficiency. PMID- 22096291 TI - Foreign body removal with repair of iatrogenic tracheo-bronchial tear repair: An anesthetic challenge. AB - Foreign body aspiration into the airway is common in the pediatric age group and its anesthetic management is a challenge. Iatrogenic tracheo-bronchial injury further worsens the situation. Flexible pediatric fiberscope is the gold standard for securing the airway in cases of airway injury. We present a case of a 7-year old girl who presented to the hospital with signs and symptoms of foreign body aspiration and suspected tracheo-bronchial tree injury. The impacted foreign body was removed by rigid bronchoscopy and the presence of a tracheo-bronchial tear was confirmed. To repair the airway tear, thoracotomy was planned necessitating one lung ventilation. A pediatric flexible fiberscope was not available, so left endobronchial intubation for one lung ventilation was done with the help of an airway exchange catheter using a rigid bronchoscope as a conduit. Subsequent intra-operative and post-operative period were uneventful. PMID- 22096292 TI - Antiplatelet therapy in patients with coronary artery stents for noncardiac surgery: Role of thromboelastography. AB - The perioperative course of the patients who have undergone coronary stent placement was studied. These patients were on dual antiplatelet therapy and were posted for noncardiac surgery. Clopidogrel had been discontinued for a variable duration before noncardiac surgery. Thromboelastography (TEG) was performed preoperatively to assess their fitness for surgery. The surgery and the postoperative period were uneventful in all the patients. There was no incidence of increased bleeding in any of the patients. Blood transfusion was not required in any patient. We concluded that standard TEG can be used when in dilemma about the fitness of the patient for surgery. Although there are clear guidelines about the patients who are on dual antiplatelet therapy, in clinical practice, it is important to weigh the risk-benefit to the advantage of the patient. If we stop the dual antiplatelet therapy in a patient with drug eluting stent within 1 year of implantation, the risk of major adverse cardiac event increases many fold. If we continue clopidogrel and aspirin during surgery, the risk of bleeding increases but is not life-threatening, except when surgery is performed in closed spaces. Thus, to continue dual antiplatelet medication intraoperatively is better than to stop it. If the medicine has to be withheld, it should be withheld for the minimal possible duration and a TEG should be performed. PMID- 22096293 TI - Arrhythmias following spinal anesthesia for cesarean delivery - Is Wenckebach common? AB - Arrhythmias in pregnancy are common and may cause concern for the well-being of both mother and fetus. Generally, no previous history of heart disease is elicited and majority of the arrhythmias are benign. Bradycardia is commonly seen following subarachnoid block for cesarean section. However, the incidence of subsequent heart block is low. This case report highlights the occurrence of perioperative arrhythmias following sympathetic blockade in pregnant patients and their early detection by vigilant monitoring. PMID- 22096294 TI - Use of intubating laryngeal mask airway in a morbidly obese patient with chest trauma in an emergency setting. AB - A morbidly obese male who sustained blunt trauma chest with bilateral pneumothorax was referred to the intensive care unit for management of his condition. Problems encountered in managing the patient were gradually increasing hypoxemia (chest trauma with multiple rib fractures with lung contusions) and difficult mask ventilation and intubation (morbid obesity, heavy jaw, short and thick neck). We performed awake endotracheal intubation using an intubating laryngeal mask airway (ILMA) size 4 and provided mechanical ventilation to the patient. This report suggests that ILMA can be very useful in the management of difficult airway outside the operating room and can help in preventing adverse events in an emergency setting. PMID- 22096295 TI - Anesthetic management of a patient with sickle cell disease for common bile duct exploration. AB - Patients with sickle cell disease (SCD) may present to the anesthetist in different clinical settings like perioperative care, management of acute painful crisis and intensive therapy for acute respiratory failure. We describe the successful management of a 34-year-old female patient with SCD, posted for cholecystectomy with common bile duct exploration under general and epidural anesthesia. The importance of preoperative stabilization and careful anesthetic strategy is emphasized. PMID- 22096296 TI - Successful anesthetic management of a child with blepharophimosis syndrome and atrial septal defect for reconstructive ocular surgery. AB - Blepharophimosis syndrome is an autosomal dominant disorder characterized by eyelid malformation, involvement of reproductive system and abnormal facial morphology leading to difficult airway. We report a rare association of blepharophimosis syndrome and atrial septal defect in a 10-year-old girl who came for reconstruction surgery of eyelid. The child had dyspnea on exertion. Atrial septal defect was identified preoperatively by clinical examination and echocardiography. Anesthesia management was complicated by failure in laryngeal mask airway placement and Cobra perilaryngeal airway was subsequently used. PMID- 22096297 TI - Remifentanil apnea: Case report and review of the literature. AB - Remifentanil is an opioid analgesic frequently used in intensive care patients because of its rapid onset of action, potency, and ultra-short duration. If an excessive dose is given, it leads to rapid, short lasting, potentially life threatening side effects such as apnea, bradycadia, hypotension, and rigidity, following rapid peak serum levels. We report a 36-year-old woman developing apnea with bradycardia and hypotension, following an infusion in the central venous catheter lumen that had been used for remifentanil till tracheal extubation. The patient was immediately ventilated with bag-valve-mask and improved within 8 minutes. She became fully awake, heart rate and blood pressure returned to normal, and oxygen saturation improved to 100%. Acute care physicians, intensivists, anesthesiologists, and critical care nurses should be aware of this clinical problem in order prevent it as much as possible and to initiate immediate resuscitative measures. PMID- 22096298 TI - Unilateral pulmonary edema after laparoscopic nephrectomy. AB - Unilateral-dependent pulmonary edema though reported in laparoscopic donor nephrectomies, has not been reported after laparoscopic non-donor nephrectomies. A 75-kg, 61-year-old man, a diagnosed case of right renal cell carcinoma was scheduled for laparoscopic nephrectomy. After establishing general anesthesia, the patient was positioned in the left-sided modified kidney (flank) position. During the 5.75-hour procedure, he was hemodynamically stable except for a transient drop in blood pressure immediately after positioning. Intra-abdominal pressure was maintained less than 15 mmHg throughout the procedure. Blood loss was approximately 50 mL and urine output was 100 mL in the first hour followed by a total of 20 mL in the next 4.75 hours. Total fluid received during the procedure included 1.5 L of Ringer's lactate and 1.0 L of 6% hydroxyethyl starch. After an uneventful procedure he developed respiratory distress in the postoperative period with a radiological evidence of dependent lung edema. Clinical and radiological improvement followed noninvasive ventilation, intravenous diuretics and oxygen therapy. PMID- 22096299 TI - Transient brachial monoparesis following epidural anesthesia for cesarean section. AB - Monoparesis following lumbar epidural block is a rare occurrence, with few cases reported in the literature. We report development of transient brachial monoparesis following epidural anesthesia in a parturient for cesarean section. The patient received a mixture of 15 mL of 2% lignocaine with 50 mcg fentanyl epidurally to achieve a blockade up to T6 level. She remained hemodynamically stable throughout the procedure, with no respiratory distress or desaturation. However, near the end of surgery, she developed weakness in the right upper limb. The weakness lasted for 90 min, followed by complete neurological recovery. Subsequent hospital stay was uneventful. PMID- 22096300 TI - Tumor lysis syndrome developing intraoperatively. AB - Tumor lysis syndrome is a potentially life threatening condition which is most commonly encountered in patients being treated with chemotherapy. We report a case of spontaneous tumor lysis syndrome that developed intraoperatively in a patient with undiagnosed Burkitt's lymphoma. Characteristic electrolyte disturbances and white emulsion like urine following laparotomy and tumor handling intraoperatively suggested the diagnosis. This is a rare perioperative complication and the report emphasizes the importance of being vigilant in recognizing the same. PMID- 22096301 TI - Supraventricular tachycardia after an intercostal nerve block with bupivacaine treated with 10% intralipid. PMID- 22096302 TI - Difficult intubation in traumatic tongue bifurcation. PMID- 22096303 TI - Malfunctioning catheter connector: An unusual and rare cause of epidural catheter blockade. PMID- 22096304 TI - Low dose spinal anesthesia for peripartum cardiomyopathy. PMID- 22096305 TI - An assembly to allow nebulization and oxygen enrichment of spontaneously breathing tracheostomized patients on T-piece. PMID- 22096306 TI - Intraventricular hemorrhage after ventriculoperitoneal shunt removal. PMID- 22096307 TI - Anesthetic management for removal of adrenocortical carcinoma with thrombus in the inferior vena cava extending to the right atrium. PMID- 22096308 TI - Comparison of propofol-based anesthesia to conventional inhalational general anesthesia for spine surgery-Few queries. PMID- 22096309 TI - Authors' reply. PMID- 22096310 TI - Endotracheal tube fixation in neurosurgical procedures operated in prone position. PMID- 22096311 TI - Intubating children with giant occipital encephalocele in lateral position: Right or left side? PMID- 22096312 TI - Ventilator malfunction. PMID- 22096314 TI - Structure pre-requisites for isoflavones as effective antibacterial agents. AB - Recent reports reveal that there is increasing incidence of infections of multidrug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Flavonoids and related compounds have been shown to possess potent antimicrobial activities. Most of the flavonoids are considered as constitutive antimicrobial substances recently termed as "Phytoanticipins," especially those belonging to prenylated flavonoids and isoflavones. The current review highlights the structure prerequisites for isoflavones as antibacterial agents. Structure-activity relationship (SAR) conclusions have been drawn by comparing the reported minimum inhibitory concentration values for the various isoflavones against S. aureus and MRSA. There exists a significant co-relationship between the presence of certain functional groups (prenyl group, phenolic hydroxyl) at particular positions and antibacterial activity of the compounds. These trends have been postulated with a view of assisting better drug designing of future next-generation antiinfectives, particularly against the bothersome multidrug-resistant microbes. The SAR of these isoflavones has also proved to be a basis to explore the mechanism of antibacterial action. Thus, the study would prove extremely useful to synthesize antibacterial isoflavones in future, which would eventually be beneficial for optimizing the lead molecule for the antibacterial action. PMID- 22096313 TI - Flavonoids: A versatile source of anticancer drugs. AB - An exponential increase in the number of studies investigating how different components of the diet interact at the molecular and cellular level to determine the fate of a cell has been witnessed. In search for anticancer drugs compelling data from laboratories, epidemiologic investigations, and human clinical trials showed that flavonoids have important effects on cancer chemoprevention and chemotherapy. In many molecular mechanisms of action for prevention against cancer, flavonoids play a major role by interacting between different types of genes and enzymes. Many mechanisms of action have been identified, including carcinogen inactivation, antiproliferation, cell cycle arrest, induction of apoptosis, inhibition of angiogenesis, antioxidation, and reversal of multidrug resistance or a combination of these mechanisms. This review focuses on the anticancer activity of flavonoids as well as their molecular mechanisms, including the treatment of mammary and prostate cancer. This review also highlights some advanced derivatives of flavonoids, which play an important role against cancer. PMID- 22096315 TI - alpha-glucosidase inhibitors from plants: A natural approach to treat diabetes. AB - Diabetes is a common metabolic disease characterized by abnormally high plasma glucose levels, leading to major complications, such as diabetic neuropathy, retinopathy, and cardiovascular diseases. One of the effective managements of diabetes mellitus, in particular, non-insulin-dependent diabetes mellitus (NIDDM) to decrease postprandial hyperglycemia, is to retard the absorption of glucose by inhibition of carbohydrate hydrolyzing enzymes, such as alpha-glucosidase and alpha-amylase, in the digestive organs. alpha-Glucosidase is the key enzyme catalyzing the final step in the digestive process of carbohydrates. Hence, alpha glucosidase inhibitors can retard the liberation of d-glucose from dietary complex carbohydrates and delay glucose absorption, resulting in reduced postprandial plasma glucose levels and suppression of postprandial hyperglycemia. In recent years, many efforts have been made to identify effective alpha glucosidase inhibitors from natural sources in order to develop a physiologic functional food or lead compounds for use against diabetes. Many alpha glucosidase inhibitors that are phytoconstituents, such as flavonoids, alkaloids, terpenoids,anthocyanins, glycosides, phenolic compounds, and so on, have been isolated from plants. In the present review, we focus on the constituents isolated from different plants having alpha-glucosidase inhibitory potency along with IC50 values. PMID- 22096316 TI - Role of natural herbs in the treatment of hypertension. AB - Hypertension (HTN) is the medical term for high blood pressure. It is dangerous because it makes the heart work too hard and contributes to atherosclerosis (hardening of arteries), besides increasing the risk of heart disease and stroke. HTN can also lead to other conditions such as congestive heart failure, kidney disease, and blindness. Conventional antihypertensives are usually associated with many side effects. About 75 to 80% of the world population use herbal medicines, mainly in developing countries, for primary health care because of their better acceptability with human body and lesser side effects. In the last three decades, a lot of concerted efforts have been channeled into researching the local plants with hypotensive and antihypertensive therapeutic values. The hypotensive and antihypertensive effects of some of these medicinal plants have been validated and others disproved. However, ayurvedic knowledge needs to be coupled with modern medicine and more scientific research needs to be done to verify the effectiveness, and elucidate the safety profile of such herbal remedies for their antihypertensive potential. PMID- 22096317 TI - Phytoestrogens in postmenopausal indications: A theoretical perspective. AB - This review discusses plant-derived compounds with estrogenic activity. The authors rightly emphasize the need for the intake of foods containing phytoestrogens in view of their positive effects on postmenopausal indications. This is particularly significant in the light of the current wave of enthusiasm for vegetarian food, in general, and phytoestrogens, in particular. Phytoestrogens are plant-derived hormone-like diphenolic compounds of dietary origin. These compounds are weakly estrogenic and could play a role in the prevention of other estrogen-related conditions, namely, cardiovascular diseases, menopausal symptoms, postmenopausal osteoporosis, neuroprotective effects, and hormone-dependent cancers (breast and endometrium cancer). PMID- 22096318 TI - Novel approaches for stability improvement in natural medicines. AB - Natural product market has seen tremendous growth in the last few years. It results in the formulation of a number of proprietary herbal products, majority of them being multi-component formulations. With the advancement of herbal drug treatments, it has now been observed that many of the constituents present in the drug may react with each other, raising the serious concern about the stability of such formulations which is an important issue in the field of phytochemistry and natural medicines. Natural products are often prone to deterioration, especially during storage, leading to loss of active component, production of metabolites with no activity and, in extreme cases, production of toxic metabolites. This area needs to be addressed in order to determine the efficacy of the formulation. Understanding the problems related to natural product stability can give the idea of dealing with the stability issues. Modifications of the conventional herbal formulations can deal with the stability problems to a large extent. This article deals with the stability problems and is aimed to provide some tools and techniques to increase stability of natural medicines and herbal formulations. PMID- 22096319 TI - A review on Balanites aegyptiaca Del (desert date): phytochemical constituents, traditional uses, and pharmacological activity. AB - Balanites aegyptiaca Del. (Zygophyllaceae), known as 'desert date,' is spiny shrub or tree up to l0 m tall, widely distributed in dry land areas of Africa and South Asia. It is traditionally used in treatment of various ailments i.e. jaundice, intestinal worm infection, wounds, malaria, syphilis, epilepsy, dysentery, constipation, diarrhea, hemorrhoid, stomach aches, asthma, and fever. It contains protein, lipid, carbohydrate, alkaloid, saponin, flavonoid, and organic acid. Present review summarizes the traditional claims, phytochemistry, and pharmacology of B. aegyptiaca Del reported in scientific literature. PMID- 22096320 TI - Cuminum cyminum and Carum carvi: An update. AB - Cuminum cyminum and Carum carvi are the sources of cumin and caraway seeds respectively, which have been used since antiquity for the treatment of various indications in traditional healing systems in wide geographical areas. Cumin and caraway seeds are rich sources of essential oils and have been actively researched for their chemical composition and biological activities. In recent times (especially during the last 3 years) considerable progress has been made regarding validation of their acclaimed medicinal attributes by extensive experimental studies. In this attempt many novel bioactivities have been revealed. This review highlights the significance of cumin and caraway as potential source of diverse natural products and their medicinal applications. PMID- 22096321 TI - Tamarindus indica: Extent of explored potential. AB - Tamarindus is a monotypic genus and belongs to the subfamily Caesalpinioideae of the family Leguminosae (Fabaceae), Tamarindus indica L., commonly known as Tamarind tree is one of the most important multipurpose tropical fruit tree species in the Indian subcontinent. Tamarind fruit was at first thought to be produced by an Indian palm, as the name Tamarind comes from a Persian word "Tamar I-hind," meaning date of India. Its name "Amlika" in Sanskrit indicates its ancient presence in the country. T.indica is used as traditional medicine in India, Africa, Pakistan, Bangladesh, Nigeria,and most of the tropical countries. It is used traditionally in abdominal pain, diarrhea and dysentery, helminthes infections, wound healing, malaria and fever, constipation, inflammation, cell cytotoxicity, gonorrhea, and eye diseases. It has numerous chemical values and is rich in phytochemicals, and hence the plant is reported to possess antidiabetic activity, antimicrobial activity, antivenomic activity, antioxidant activity, antimalarial activity, hepatoprotective activity, antiasthmatic activity, laxative activity, and anti-hyperlipidemic activity. Every part of the plant from root to leaf tips is useful for human needs. Thus the aim of the present review is to describe its morphology, and explore the phytochemical constituents, commercial utilization of the parts of the plant, and medicinal and pharmacologic activities so that T. indica's potential as multipurpose tree species can be understood. PMID- 22096322 TI - Chamomile (Matricaria chamomilla L.): An overview. AB - Chamomile (Matricaria chamomilla L.) is a well-known medicinal plant species from the Asteraceae family often referred to as the "star among medicinal species." Nowadays it is a highly favored and much used medicinal plant in folk and traditional medicine. Its multitherapeutic, cosmetic, and nutritional values have been established through years of traditional and scientific use and research. Chamomile has an established domestic (Indian) and international market, which is increasing day by day. The plant available in the market many a times is adulterated and substituted by close relatives of chamomile. This article briefly reviews the medicinal uses along with botany and cultivation techniques. Since chamomile is a rich source of natural products, details on chemical constituents of essential oil and plant parts as well as their pharmacological properties are included. Furthermore, particular emphasis is given to the biochemistry, biotechnology, market demand, and trade of the plant. This is an attempt to compile and document information on different aspects of chamomile and highlight the need for research and development. PMID- 22096323 TI - Ficus hispida Linn.: A review of its pharmacognostic and ethnomedicinal properties. AB - Ficus hispida (FH) Linn. is a moderate sized tree found throughout the year and is grown wild or cultivated for its edible fruits and folklore value. Traditionally, different parts of the plant have been used in the treatment of ulcers, psoriasis, anemia, piles jaundice, vitiligo, hemorrhage, diabetes, convulsion, hepatitis, dysentery, biliousness, and as lactagogue and purgative. FH contains wide varieties of bioactives from different phytochemical groups like alkaloids, carbohydrates, proteins and amino acids, sterols, phenols, flavonoids, gums and mucilage, glycosides, saponins, and terpenes. Various scientific works have been published to establish the scientific basis of traditional medicinal values attributed to FH. Furthermore, newer pharmacological activities like antineoplastic, cardioprotective, neuroprotective and anti-inflammatory effects were also reported recently. Till now, no work has been published to elaborate the pharmacognostic features of FH Linn. The present review is, therefore, an effort to give a detailed account on its pharmacognosy and phytochemistry, and an extensive survey on its pharmacological activities. Moreover, we are trying to establish the mechanism of action behind its earlier reported pharmacology. The review also looks at the future formulation based delivery approaches of its lipophilic bioactives, which is done to enhance its dissolution so as to increase its bioavailability, and thus the associated pharmacological action. PMID- 22096325 TI - Launch of Journal of Natural Science, Biology and Medicine for the global scientific audience. PMID- 22096326 TI - Orodispersible tablets: A new trend in drug delivery. AB - The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other oral formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to super disintegrants in the formulation. Thus this type of drug delivery helps a proper peroral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method of preparation is the compression method. Other special methods are molding, melt granulation, phase-transition process, sublimation, freeze-drying, spray-drying, and effervescent method. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test, and dissolution test. PMID- 22096324 TI - Feverfew (Tanacetum parthenium L.): A systematic review. AB - Feverfew (Tanacetum parthenium L.) (Asteraceae) is a medicinal plant traditionally used for the treatment of fevers, migraine headaches, rheumatoid arthritis, stomach aches, toothaches, insect bites, infertility, and problems with menstruation and labor during childbirth. The feverfew herb has a long history of use in traditional and folk medicine, especially among Greek and early European herbalists. Feverfew has also been used for psoriasis, allergies, asthma, tinnitus, dizziness, nausea, and vomiting. The plant contains a large number of natural products, but the active principles probably include one or more of the sesquiterpene lactones known to be present, including parthenolide. Other potentially active constituents include flavonoid glycosides and pinenes. It has multiple pharmacologic properties, such as anticancer, anti-inflammatory, cardiotonic, antispasmodic, an emmenagogue, and as an enema for worms. In this review, we have explored the various dimensions of the feverfew plant and compiled its vast pharmacologic applications to comprehend and synthesize the subject of its potential image of multipurpose medicinal agent. The plant is widely cultivated to large regions of the world and its importance as a medicinal plant is growing substantially with increasing and stronger reports in support of its multifarious therapeutic uses. PMID- 22096327 TI - Impact of uncertainty on sound perception. AB - In the auditory study, masking caused by sound uncertainty is a hot topic because research on this topic has a potential to be applied to improve human perception in a real world. This article introduces the origination of the study on this so called informational masking and lists some key results obtained. The informational masking is widely accepted to result from the central auditory system since the classical auditory peripheral model fails to account for the data. This article reviewed the currently most satisfactory model on informational masking and its ability and disability in accounting for current experimental data. In the end, potential sources of the informational masking are discussed as an indication for the future research direction. The review is mostly based on articles published in JASA and JARO, the two most prestigious journals in the auditory study. PMID- 22096328 TI - Geochemical studies of fluoride and other water quality parameters of ground water in Dhule region Maharashtra, India. AB - This study has been carried out to find out the water pollutants and to test the suitability of water for drinking and irrigation purposes in Dhule and surrounding areas in Maharashtra State in India. The analysis was carried out for the parameters pH, DO (dissolved oxygen), BOD (biological oxygen demand), Cl-, NO3-, F-, S(2)-, total alkalinity, total solid, total dissolved solids (TDS), total suspended solids (TSS), total hardness, calcium, magnesium, carbonate and noncarbonate hardness, and concentrations of calcium and magnesium. These parameters were compared against the standards laid down by World Health Organization (WHO) and Indian Council of Medical Research (ICMR) for drinking water quality. High levels of NO(3)-, Cl-, F-, S(2)-, total solid, TDS, TSS, total hardness, magnesium and calcium have been found in the collected samples. From these observations, it has been found that fluoride is present as per the permissible limit (WHO 2003) in some of the villages studied, but both fluoride and nitrate levels are unacceptable in drinking water samples taken from several villages in Dhule. This is a serious problem and, therefore, requires immediate attention. Excess of theses impurities in water causes many diseases in plants and animals. This study has been carried out to find out the water pollutants and to test the suitability of water for drinking and irrigation purposes in Dhule and surrounding areas in Maharashtra. PMID- 22096329 TI - Antibacterial activity of garlic extract on streptomycin-resistant Staphylococcus aureus and Escherichia coli solely and in synergism with streptomycin. AB - This study focuses the significant antibacterial activity of Garlic (Allium sativum Linn.) extract on streptomycin-resistant strains solely and in synergism with streptomycin. Gram-positive Staphylococcus aureus ATCC BAA 1026 and gram negative Escherichia coli ATCC 10536 were made resistant to standard antibiotic streptomycin used as a control in the experiment. Zones of inhibition of different treatment groups were measured by agar-well-diffusion assay and compared with control. Statistical comparison of sole extract and streptomycin synergism with streptomycin control had proved it significant. PMID- 22096330 TI - Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8 tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe. AB - The ability of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid), a water-soluble vitamin E analogue, to prevent oxidative damages is well characterized, but the mechanisms underlying it remain unclear. The protective effect of Trolox pre-treatment on H(2)O(2)-induced toxicity might be attributed to the decreased cellular permeability to H(2)O(2) or in vitro scavenging activity of Trolox, induction of antioxidant enzymes or the direct scavenging activity of Trolox. The results obtained rule out the first and second possibilities and intracellular scavenging activity was found to be the mechanism whereby Trolox confers protection. This was confirmed by measuring protein oxidation (levels), and the observed decrease in proteasomal activity indicated that the decrease in protein carbonyls was due to Trolox scavenging activity rather than proteasome activation. In conclusion, the intracellular scavenging activity of Trolox is a key protective mechanism against H(2)O(2). These findings obtained in Schizosaccharomyces pombe, a good model organism for eukaryotic cells, can be used as standard protocols for investigating the antioxidant activity of pure or complex potential antioxidants. PMID- 22096331 TI - Anticandidal activity of endemic Salvia potentillifolia Boiss. and Heldr. ex Bentham and Origanum hypericifolium Schwartz and P.H. Davis in Turkey. AB - This study established baseline data on lytic anticandidal activities of endemic species Origanum hypericifolium and Salvia potentillifolia naturally distributed in Denizli and its environment. Stream distillation was used to isolate the unfatty polar part and clinical isolated Candida spp. strains were subcultured to sabouraud dextrose agar. Lytic anticandidal activities of unfatty polar parts were evaluated by enzyme-linked calorimetric method against 93 clinical isolates belonging to Candida albicans, C. tropicalis, C. glabrata, C. krusei, C. Kefyr, and C. parapsilosis. As a result, two (2.15%) strains of C. glabrata among tested pathogenic 93 clinical isolates of Candida strains were found to be sensitive to S. potentillifolai. However, each strain of C. albicans and C. tropicalis was found to be sensitive to O. hypericifolium. Results indicated that O. hypericifolium and S. potentillifolia had a potential of being used in food and medicine because of their anticandidal activity. PMID- 22096332 TI - HindIII-based restriction fragment length polymorphism in hemophilic and nonhemophilic patients. AB - Hemophilia A is most common recessively inherited bleeding disorder, which affect one in five thousand male births throughout the world. In most of the hemophilic A patients, no common mutation is easily identifiable. This limitation has been overcome by the use of polymorphic DNA marker, i.e., restriction fragment length polymorphism (RFLP). This marker of polymorphism could only be detected by amplifying the polymorphic region and digestion the polymerase chain reaction (PCR) product with the restriction enzyme (PCR-RFLP), i.e., HindIII. The polymorphic region of HindIII is 608 bp in length and after the restriction digestion, different sizes of fragments, i.e., 427 and 181 bp were, respectively, obtained. However, in homozygous (+/+) condition three bands of 427, 100, and 81 bp were obtained and in the other negative allelic homozygous condition (-/-) two bands of 427 and 181 bp were obtained. Similarly fragments of different sizes, i.e., 427, 181, 100, and 81 bp were obtained in heterozygous conditions. Therefore, in this study, we have analyzed the factor VIII gene in the 17 different families using restriction enzyme HindIII-based RFLP molecular marker technique. Out of these, the observed heterozygosity for HindIII was found 47.5%, whereas, for positive allele it was 26%, and for negative allele the frequency was 74%. PMID- 22096333 TI - Antioxidant and free-radical-scavenging effects of fruits of Dregea volubilis. AB - This study evaluated the in vitro antioxidant potential of petroleum ether (60-80 degrees C), chloroform, and methanol extract of the fruits of Dregea volubilis Benth (Asclepiadaceae). The different antioxidant assays, including total antioxidant activity, reducing power, free radical, super oxide anion radical, nitric oxide scavenging, lipid peroxidation, and total phenolic content were studied. The extracts exhibited potent total antioxidant activity that increased with increasing amount of extract concentration, which was compared with standard drug vitamin C at different concentrations as extracts. The different concentrations of all the extracts and vitamin C showed inhibition on lipid peroxidation. In addition, all the extracts had effective reducing power, free radical scavenging, super oxide anion scavenging, nitric oxide scavenging, lipid peroxidation, and total phenolic content depending on concentration. These various antioxidant activities were compared with standard antioxidant such as vitamin C at different concentration as different extracts. PMID- 22096334 TI - A study on poisoning cases in a tertiary care hospital. AB - Acute poisoning with various substance is common everywhere. The earlier the initial resuscitations, gastric decontamination and use of specific antidotes, the better the outcome. The aim of this study was to characterize the poisoning cases admitted to the tertiary care hospital, Warangal district, Andhra Pradesh, Southern India. All cases admitted to the emergency department of the hospital between the months of January and December, 2007, were evaluated retrospectively. We reviewed data obtained from the hospital medical records and included the following factors: socio-demographic characteristics, agents and route of intake and time of admission of the poisoned patients. During the outbreak in 2007, 2,226 patients were admitted to the hospital with different poisonings; the overall case fatality rate was 8.3% (n = 186). More detailed data from 2007 reveals that two-third of the patients were 21-30 years old, 5.12% (n = 114) were male and 3.23% (n = 72) were female, who had intentionally poisoned themselves. In summary, the tertiary care hospitals of the Telangana region, Warangal, indicate that significant opportunities for reducing mortality are achieved by better medical management and further sales restrictions on the most toxic pesticides. This study highlighted the lacunae in the services of tertiary care hospitals and the need to establish a poison information center for the better management and prevention of poisoning cases. PMID- 22096335 TI - Periodontitis: A risk for delivery of premature labor and low-birth-weight infants. AB - Periodontitis is a destructive inflammatory disease of the supporting tissues of the teeth and is caused by specific microorganisms or group of specific microorganisms. The association of periodontal infection with organ systems like cardiovascular system, endocrine system, reproductive system, and respiratory system makes periodontal infection a complex multiphase disease. Inflamed periodontal tissues produce significant amounts of proinflammatory cytokines, mainly interleukin 1-beta (IL-1beta), IL-6, prostaglandin E2, and tumor necrosis factor-alpha (TNF-alpha), which may have systemic effects on the host. Low birth weight, defined as birth weight less than 2,500 g, continues to be a significant public health issue in both developed and developing countries. Research suggests that the bacteria that cause inflammation in the gums can actually get into the bloodstream and target the fetus, potentially leading to premature labor and low birth-weight (PLBW) babies. One reasonable mechanism begins with deleterious effects of endotoxins released from Gram-negative bacteria responsible for periodontal disease. Hence periodontal disease appears to be an independent risk factor for PLBW and there is a need to expand preventive measures for pregnant women in harmonization with the gynecological and dental professions. PMID- 22096336 TI - Stem cells: An overview with respect to cardiovascular and renal disease. AB - In recent years, there has been a tremendous increase in the understanding of stem cell biology. Stem cells have clonogenic and self-renewing capabilities, and under certain conditions, can differentiate into multiple lineages of mature cells. Recent studies have shown that adult stem cells can be isolated from a wide variety of tissues, including bone marrow, peripheral blood, muscle, and adipose tissue. The potential clinical applications lead to an extended interest in the use of stem cells in many medical disciplines. In this article, we present an overview of stem cells with special reference to cardiovascular and renal diseases treatments by stem cells. PMID- 22096337 TI - Role of antibodies in cancer targeting. AB - The development of chemotherapeutic agents capable of specifically eliminating tumor cells has been a great challenge since these agents cannot differentiate between normal body cells and tumor cells. Enhanced elimination of cancer cells without affecting normal body cells can be achieved by developing strategies which can enable drug targeting. With recent advances in antibody engineering strategies, the development of different antibody-associated tumor-targeted delivery systems for chemotherapy, chemoprevention, and early cancer diagnosis has become possible. In this review, the role of antibodies for cancer diagnosis, chemoprevention, and chemotherapy will be discussed with an emphasis on recent advances in antibody engineering. PMID- 22096338 TI - TUD-1: synthesis and application of a versatile catalyst, carrier, material... AB - The three-dimensional sponge-like mesoporous material TUD-1 is straightforward to prepare. Its synthesis can readily be modified to introduce metals into the framework of TUD-1, imparting many different catalytic activities. M-TUD-1 catalysts have proven to be very active, unlimited by diffusion and very stable. By combining two metals into one TUD-1 catalyst, synergy between Lewis and Bronsted acid sites could be induced; incorporation of zeolites similarly gave rise to synergy. In addition to successful applications in redox-, acid- and photo-catalysis TUD-1 proved to be an excellent carrier material for catalysts, enabling new applications. TUD-1 was used as a contrast agent and drug delivery system, indicating that this material is but at the beginning of its potential applications. PMID- 22096339 TI - Occupational chemical burns: a 2-year experience in the emergency department. AB - Chemical burn injuries are a result of exposure to acid, alkali, or organic compounds. In this retrospective study, a total of 21 patients suffering occupational chemical burns, came to the emergency room at the University General Hospital of Alexandroupolis, from 2008 to 2010; 76.2% were workers, 19% were farmers, and 4.8% were desk officers. The majority of burns were due to exposure to acid (61.9%). Upper extremities were the most frequently injured area followed by the lower extremities and thorax. None of the patients needed further hospital care, but in the follow-up, four of the patients suffered keloid. Proper surgical treatment at the emergency room decreases the length of hospital stay for patients who suffer chemically induced burns. PMID- 22096340 TI - Patient-Centered Medical Home in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating but preventable and treatable disease characterized by cough, phlegm, dyspnea, and fixed or incompletely reversible airway obstruction. Most patients with COPD rely on primary care practices for COPD management. Unfortunately, only about 55% of US outpatients with COPD receive all guideline-recommended care. Proactive and consistent primary care for COPD, as for many other chronic diseases, can reduce hospitalizations. Optimal chronic disease management requires focusing on maintenance rather than merely acute rescue. The Patient-Centered Medical Home (PCMH), which implements the chronic care model, is a promising framework for primary care transformation. This review presents core PCMH concepts and proposes multidisciplinary team-based PCMH care strategies for COPD. PMID- 22096341 TI - Does evidence really matter? Professionals' opinions on the practice of early mobilization after stroke. AB - INTRODUCTION: Early mobilization after stroke may be important for a good outcome and it is currently recommended in a range of international guidelines. The evidence base, however, is limited and clear definitions of what constitutes early mobilization are lacking. AIMS: To explore stroke care professionals' opinions about (1) when after stroke, first mobilization should take place, (2) whether early mobilization may affect patients' final outcome, and (3) what level of evidence they require to be convinced that early mobilization is beneficial. METHODS: A nine-item questionnaire was used to interview stroke care professionals during a conference in Sydney, Australia. RESULTS: Among 202 professionals interviewed, 40% were in favor of mobilizing both ischemic and hemorrhagic stroke patients within 24 hours of stroke onset. There was no clear agreement about the optimal time point beyond 24 hours. Most professionals thought that patients' final motor outcome (76%), cognitive outcome (57%), and risk of depression (75%) depends on being mobilized early. Only 19% required a large randomized controlled trial or a systematic review to be convinced of benefit. CONCLUSION: The spread in opinion reflects the absence of clear guidelines and knowledge in this important area of stroke recovery and rehabilitation, which suggests further research is required. PMID- 22096342 TI - Role of toll-like receptor 4 in acute neutrophilic lung inflammation induced by intratracheal bacterial products in mice. AB - BACKGROUND: Toll-like receptors (TLRs) represent a conserved family of innate immune recognition receptors. Among TLRs, TLR4 is important for the recognition of Gram-negative bacteria, whereas TLR2 recognizes cell wall constituents of Gram positive microorganisms, such as peptidoglycan (PGN). METHODS: To evaluate the role of TLR4 in the pathogenesis of acute lung injury induced by Escherichia coli endotoxin (lipopolysaccharide; LPS) or PGN, we compared inflammatory cell accumulation in bronchoalveolar lavage (BAL) fluid and lung pathology between C3H/HeJ (TLR4 mutant) and wild-type C3H/HeN mice. The levels of proinflammatory cytokines and chemokines in plasma and BAL fluid and nuclear factor-kappaB (NF kappaB) translocation in the lung were also evaluated. RESULTS: In C3H/HeJ mice, LPS-induced neutrophil emigration was significantly decreased compared with C3H/HeN mice, whereas PGN-induced neutrophil emigration did not differ. Differential cell count in BAL fluid revealed comparable neutrophil recruitment in the alveolar space. In TLR4 mutant mice, LPS-induced upregulation of tumor necrosis factor-alpha (TNF-alpha), KC, and CXCL10 in plasma and BAL fluid was attenuate, which was not different after PGN. NF-kappaB translocation in the lung was significantly decreased in C3H/HeJ compared with C3H/HeN mice, whereas PGN induced NF-kappaB translocation was not different. CONCLUSION: These results suggest that TLR4 mediates inflammatory cascade induced by Gram-negative bacteria that is locally administered. PMID- 22096343 TI - No evidence for activation of T(H)1 or T(H)17 pathways in unstimulated peripheral blood mononuclear cells from children with beta-cell autoimmunity or T1D. AB - INTRODUCTION: The balance between T(H)1, T(H)2, T(H)17, and regulatory T cells has been suggested to be disturbed in type 1 diabetes (T1D). We investigated this balance in peripheral blood mononuclear cells (PBMC) from children at risk of developing T1D and children with T1D. METHODS: We studied PBMC expression levels of markers related to T(H)1 (T-bet, IL-12Rbeta(1), IL-12Rbeta(2)), T(H)2 (GATA-3, IL-4Ralpha), T(H)17 (IL-17A), and regulatory T cells (Foxp3, ICOS, and CTLA-4) with real-time polymerase chain reaction from 17 children with T1D, 13 children with beta-cell autoimmunity, 15 children with T1D risk-associated human leukocyte antigen (HLA) haplotypes, and 24 healthy, control children. RESULTS: We observed decreased expression levels of GATA-3 by PBMC of healthy children with autoantibodies compared to healthy, control children (p = 0.014) or children with HLA risk alleles (p = 0.032). Children with T1D demonstrated lower expression levels of T-bet, IL-12Rbeta(1), and IL-4Ralpha both at diagnosis and 12 months later. CONCLUSION: We found no indication of aberrant activation of T(H)1, T(H)17, or Treg in peripheral blood from children with or without risk of T1D. The observed immunological differences between children at risk of and with T1D should be considered when immunopathogenesis of beta-cell destruction is studied. PMID- 22096344 TI - Synergistic induction of CX3CL1 by TNF alpha and IFN gamma in osteoblasts from rheumatoid arthritis: involvement of NF-kappa B and STAT-1 signaling pathways. AB - To explore the regulation of CX3CL1 in inflammatory bone diseases, CX3CL1 expression by osteoblasts (OB) was examined. Human OB isolated from rheumatoid arthritis (RA) patients, osteoarthritis patients, and normal individuals were incubated in the presence of cytokines. Soluble CX3CL1 levels were determined with an enzyme-linked immunosorbent assay. Expression of CX3CL1 mRNA was examined using quantitative real-time polymerase chain reaction. Although tumor necrosis factor (TNF)-alpha or interferon (IFN)-gamma alone RA OB induced negligible CX3CL1 secretion, the combination of TNF-alpha and IFN-gamma induced dramatic increases in both soluble CX3CL1 protein and mRNA transcripts. This synergistic effect was more pronounced in OB from RA than in OB from either osteoarthritis or normal individuals. The expression of CX3CL1 was markedly reduced by specific inhibitors of the nuclear factor-kappaB (NF-kappaB) or STAT-1 transcription factor. These findings suggest that osteoblasts are an important cellular source of CX3CL1 and may play roles in inflammatory bone/joint diseases. PMID- 22096345 TI - Neuroinflammation and tumor necrosis factor signaling in the pathophysiology of Alzheimer's disease. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects nearly one in two individuals over 90 years of age. Its neuropathological hallmarks are accumulation of extraneuronal plaques of amyloid-beta (Abeta), the presence of neurofibrillary tangles formed by aberrantly hyperphosphorylated tau, progressive synaptic loss, and neurodegeneration which eventually results in decline of memory and cognitive faculties. Although the etiology of sporadic AD in humans is unknown, mutations in amyloid precursor protein or components of its processing machinery (beta-secretase and gamma-secretase) result in overproduction of Abeta1-40 and 1-42 peptides and are sufficient to cause disease. In this review, we highlight the experimental and clinical evidence that suggests a close association between neuro-inflammation and AD pathogenesis. Overproduction of inflammatory mediators in the brain occurs when microglia, which are often found in close physical association with amyloid plaques in AD brains, become chronically activated. It has been proposed that elevated levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF), may inhibit phagocytosis of Abeta in AD brains thereby hindering efficient plaque removal by resident microglia. In support of this idea, the bacterial endotoxin lipopolysaccharide, a potent trigger of inflammation that elicits production of TNF and many other cytokines, can accelerate the appearance and severity of AD pathology in several animal models of AD. We review the evidence implicating TNF signaling in AD pathology and discuss how TNF-dependent processes may contribute to cognitive dysfunction and accelerated progression of AD. We conclude by reviewing the observations that provide compelling rationale to investigate the extent to which new therapeutic approaches that selectively target the TNF pathway modify progression of neuropathology in pre-clinical models of AD as well as the promising findings with the use of nonsteroidal anti-inflammatory drugs and recent clinical trials with Abeta immunotherapy. PMID- 22096346 TI - Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite. AB - The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%-0.2%, w/v). Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p < 0.01), supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 MUM), suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia. PMID- 22096349 TI - Comparisons of different mean airway pressure settings during high-frequency oscillation in inflammatory response to oleic acid-induced lung injury in rabbits. AB - PURPOSE: The present study was designed to examine effects of different mean airway pressure (MAP) settings during high-frequency oscillation (HFO) on oxygenation and inflammatory responses to acute lung injury (ALI) in rabbits. METHODS: Anesthetized rabbits were mechanically ventilated with a conventional mechanical ventilation (CMV) mode (tidal volume 6 ml/kg, inspired oxygen fraction [F(Io2)] of 1.0, respiratory rate [RR] of 30/min, positive end-expiratory pressure [PEEP] of 5 cmH(2)O). ALI was induced by intravenous administration of oleic acid (0.08 ml/kg) and the animals were randomly allocated to the following three experimental groups; animals (n = 6) ventilated using the same mode of CMV, or animals ventilated with standard MAP (MAP 10 cmH(2)O, n = 7), and high MAP (15 cmH(2)O, n = 6) settings of HFO (Hz 15). The MAP settings were calculated by the inflation limb of the pressure-volume curve during CMV. RESULTS: HFO with a high MAP setting significantly improved the deteriorated oxygenation during oleic acid induced ALI and reduced wet/dry ratios, neutrophil counts and interleukin-8 concentration in bronchoalveolar lavage fluid, compared to those parameters in CMV and standard MAP-HFO. CONCLUSIONS: These findings suggest that only high MAP setting during HFO could contribute to decreased lung inflammation as well as improved oxygenation during the development of ALI. PMID- 22096348 TI - Inflammatory mechanisms in the lung. AB - Inflammation is the body's response to insults, which include infection, trauma, and hypersensitivity. The inflammatory response is complex and involves a variety of mechanisms to defend against pathogens and repair tissue. In the lung, inflammation is usually caused by pathogens or by exposure to toxins, pollutants, irritants, and allergens. During inflammation, numerous types of inflammatory cells are activated. Each releases cytokines and mediators to modify activities of other inflammatory cells. Orchestration of these cells and molecules leads to progression of inflammation. Clinically, acute inflammation is seen in pneumonia and acute respiratory distress syndrome (ARDS), whereas chronic inflammation is represented by asthma and chronic obstructive pulmonary disease (COPD). Because the lung is a vital organ for gas exchange, excessive inflammation can be life threatening. Because the lung is constantly exposed to harmful pathogens, an immediate and intense defense action (mainly inflammation) is required to eliminate the invaders as early as possible. A delicate balance between inflammation and anti-inflammation is essential for lung homeostasis. A full understanding of the underlying mechanisms is vital in the treatment of patients with lung inflammation. This review focuses on cellular and molecular aspects of lung inflammation during acute and chronic inflammatory states. PMID- 22096347 TI - Progress and perspectives on the role of RPE cell inflammatory responses in the development of age-related macular degeneration. AB - Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The etiology of AMD remains poorly understood and no treatment is currently available for the atrophic form of AMD. Atrophic AMD has been proposed to involve abnormalities of the retinal pigment epithelium (RPE), which lies beneath the photoreceptor cells and normally provides critical metabolic support to these light-sensing cells. Cumulative oxidative stress and local inflammation are thought to represent pathological processes involved in the etiology of atrophic AMD. Studies of tissue culture and animal models reveal that oxidative stress-induced injury to the RPE results in a chronic inflammatory response, drusen formation, and RPE atrophy. RPE degeneration in turn causes a progressive degeneration of photoreceptors, leading to the irreversible loss of vision. This review describes some of the potential major molecular and cellular events contributing to RPE death and inflammatory responses. In addition, potential target areas for therapeutic intervention will be discussed and new experimental therapeutic strategies for atrophic AMD will be presented. PMID- 22096350 TI - Etanercept, improved dosage schedules and combinations in the treatment of psoriasis: an update. AB - Etanercept, a subcutaneously administered fully human soluble tumor necrosis factor (TNF) receptor, was initially approved for the treatment of psoriasis at a dose of 25 mg twice weekly in repeated 24-week cycles with the possibility to double the dose in the first 12 weeks of the first cycle. During intermittent treatment, patients retain their ability to respond to etanercept. Recently, a new dosing schedule of etanercept 50 mg once weekly was approved, based on a study in which PASI-75 (75% improvement of Psoriasis Area and Severity Index) was achieved by 37% and 71% of patients at week 12 and 24. Another study demonstrated a PASI-75 of 57% and 69% in pediatric psoriasis patients receiving etanercept 0.8 mg/kg (up to 50 mg) once weekly for 12 and 24 weeks respectively, resulting in European approval from age 8. Based on recent clinical trials, the antipsoriatic effect of etanercept can be markedly increased in combination with acitretin, methotrexate or UVB. The combination with acitretin appears attractive because of its non-immunosuppressive and chemopreventive properties. Etanercept-methotrexate combination therapy is well established in rheumatologic patients. From a long term perspective, the combination of TNF-inhibitors with phototherapy (photocarcinogenesis) or cyclosporine (carcinogenesis, infections) warrants great caution however. Finally, combination with topical calcipotriol-betamethasone ointment may increase the speed of response to TNF-inhibitors in the first 4 weeks of treatment. PMID- 22096351 TI - Etiology and treatment of the inflammatory causes of cystoid macular edema. AB - Cystoid macular edema in its various forms can be considered one of the leading causes of central vision loss in the developed world. It occurs in a wide variety of pathologic conditions and represents the final common pathway of several basic processes. Therapeutic approaches to cystoid macular edema depend on a clear understanding of its contributing pathophysiologic mechanisms. This review will discuss the mechanism of ocular inflammation in cystoid macular edema with a particular focus on the inflammatory causes: post-operative, uveitic, and after laser procedures. A variety of pharmacologic agents targeting inflammatory molecules have been shown to reduce macular edema and improve visual function. However, the long-term efficacy and safety of most new therapies have yet to be established in controlled clinical trials. PMID- 22096352 TI - Rilonacept in the management of cryopyrin-associated periodic syndromes (CAPS). AB - Cryopyrin-associated periodic syndromes (CAPS) are a subgroup of the hereditary periodic fever syndromes, which are rare autoinflammatory and inherited disorders, characterized by recurrent inflammation and varying degrees of severity. CAPS are thought to be driven by excessive production of interleukin 1beta (IL-1beta), through over-activation of the inflammasome by gain of function mutations in the gene encoding cryopyrin (NLRP3). This conclusion is supported by the remarkable efficacy of IL-1beta blockade in these conditions. Rilonacept (Arcalyst(TM); Regeneron) is the first us Food and Drug Administration-approved treatment for familial cold autoinflammatory syndrome and Muckle-Wells syndrome and the first in a new line of drugs designed for longer-acting IL-1 blockade. Rilonacept has been associated with a decrease in disease activity, high sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) in the treatment of CAPS. The clinical safety and efficacy of rilonacept in CAPS and non-CAPS populations will be summarized in this review. Rilonacept is also beneficial for patients who tolerate injections poorly, due to an extended half-life over the unapproved CAPS treatment, anakinra, requiring weekly rather than daily self administration. Other autoinflammatory disorders may also benefit from rilonacept treatment, with clinical trials in progress for systemic onset juvenile idiopathic arthritis, gout and familial mediterranean fever. PMID- 22096353 TI - Topical alpha-selective p38 MAP kinase inhibition reduces acute skin inflammation in guinea pig. AB - Certain skin pathologies, including psoriasis, are thought to be immune-mediated inflammatory diseases. Available literature clearly indicates the involvement of inflammatory cells (neutrophils, T cells, and macrophages), their cytokines, and the p38 mitogen-activated protein kinase (MAPK) signaling pathway in the pathophysiology of psoriasis. Neutrophils play an important role in the formation of acute inflammatory changes in psoriasis. Acute inflammation or acute flares in psoriasis remain poorly addressed in clinical medicine. In this communication, we first establish a simple and reproducible model for studying neutrophil-mediated acute skin inflammation. Using the hairless guinea pig, due to the similarity of skin architecture to that of human, acute inflammation was induced with an intradermal injection of 50 MUg/mL lipopolysaccharide (LPS) in 50 MUL solution. Myeloperoxidase (MPO) activity was measured by MPO-positive neutrophils and shown to increase for 24-hours post-injection. Simultaneously, the level of phosphorylated p38 MAPK was documented for 48-hours post-LPS injection in the skin. Next, we used this model to examine the therapeutic potential of an alpha selective p38 MAPK inhibitor, SCIO-469. A comparison of topical application of SCIO-469 at 5 mg/mL or 15 mg/mL to vehicle revealed that SCIO-469 dose dependently reduces acute skin inflammation and that this effect is statistically significant at the higher dose. Further examination of tissues that received this dose also revealed statistically significant reduction of MPO activity, phosphorylated p38 MAPK, interleukin-6, and cyclooxygenase-2. These data suggest that the alpha-selective p38 MAPK inhibitor, SCIO-469, acts as a topical anti inflammatory agent via the p38 MAPK pathway to reduce neutrophil induced acute inflammation in the skin. These observations suggest that alpha-selective p38 MAPK inhibition may be an effective therapeutic strategy to manage acute skin inflammation. PMID- 22096354 TI - Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis. AB - Multiple sclerosis (MS) is chronic inflammatory and demyelinating disease with either a progressive (10%-15%) or relapsing-remitting (85%-90%) course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta 1b (IFN-beta1b) or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-beta1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN beta1b reduces the risk of development of clinically defined MS from 45% (with placebo) to 28% (with IFN-beta1b). It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-beta1b) and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-beta1b. In recommended doses IFN-beta1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non-specific reactions), insomnia, influenza-like syndrome, asthenia, headache, myalgia, hypoesthesia, nausea, paresthesia, myasthenia, chills and depression. Efficacy of IFN-beta1b in relapsing-remitting MS is higher than that of IFN-beta1a, and similar to the efficacy of glatiramer acetate. These facts promote IFN-beta1b as one of the most important drugs in the spectrum of immunological therapies for this debilitating disease. PMID- 22096356 TI - Immune response profiles after caterpillar exposure: a case report. AB - RATIONALE: The role of the immune response to caterpillar exposure is not well described. This case study is the first to report a patient who presented with an allergic reaction after exposure to the larvae of the sycamore tussock moth, Halysidota harrisii Walsh, 1864. METHODS: Blood was collected from an allergic asthmatic adult (m/42 y/o) at 2 hrs - 2 wks after contact urticaria with associated dyspnea after exposure to the larvae of the sycamore tussock moth, Halysidota harrisii Walsh, 1864. Distributions of blood lymphocytes (CD4(+), CD8(+), CD8(+)CD60(+), CD19(+), CD23(+), CD16/56(+), CD25, CD45RA(+), CD45RO(+)), monocytes (CD1d(+)), levels of serum immunoglobulins (IgM, IgG, IgA, IgE), and cytokines (IFN-gamma, IL-4, TNF-alpha) were studied (flow cytometry, nephelometry, UniCAP Total IgE Fluoroenzymeimmunoassay, cytokine ELISA, clinical toxicology). RESULTS: Numbers of CD4(+) T cells, CD25(+) cells, CD19(+) B cells, and CD1d(+) monocytes decreased (22, 27, 33, 20%, respectively) one week post reaction, CD45RA(+) naive T cells decreased at 36 hours (21%),while CD8(+)CD60(+) T cells and CD23(+) cells decreased 48 hrs (33, 74%, respectively) post reaction. In contrast, numbers of CD16/56(+) NK precursor cells increased (60%) 12 hrs, then decreased (65%) 48 hrs post reaction; other lymphocyte subsets were unaffected. Serum IgM, IgG and IgA were within normal range; however, serum IgE demonstrated a bimodal elevation at 2 hrs (15%) and one week post reaction. Levels of IFN-gamma, IL-4, and TNF-alpha were not detected in serum pre-exposure (<1.0-4.0 pg/mL). However, high levels of IFN-gamma (187-319 pg/mL) and TNF-alpha (549-749 pg/mL) were detected in serum 24-36 hrs and 3.5-24 hrs post reaction, respectively. In contrast, levels of IL-4 were undetected (<1.0 pg/mL) in serum at all time points. CONCLUSIONS: Exposure to the larvae of the sycamore tussock moth, Halysidota harrisii Walsh, 1864 may result in increased cytokine levels and blood CD16/56(+) NK precursor cells. PMID- 22096355 TI - Current perspectives on the role of IL-17 in autoimmune disease. AB - Until recently, autoimmune diseases had been categorized as either Th1- or Th2 mediated diseases. However, the discovery of a novel subset of helper T cells producing interleukin (IL)-17, ie, Th17 cells, changed this paradigm. Currently, IL-17 and Th17 cells are implicated in many autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel diseases. Such conclusions were initially drawn from observations in animal models of autoimmune diseases, and accumulating data from clinical research also support the involvement of IL-17 in human diseases as well. Reagents targeting Th17-related molecules have been under clinical investigation for some diseases but have not always been effective in controlling disease activity. Consistent with this, it has become evident that there are substantial differences in the development of Th17 cells and in the way they function in autoimmune diseases between humans and experimental animals. Thus, further investigation is needed before we can draw any conclusions about the importance of IL-17 and Th17 cells in human autoimmune diseases. PMID- 22096357 TI - Emerging therapies for treatment of multiple sclerosis. AB - In the last decade, a new armamentarium of immune-based therapies have been developed and tested in patients with multiple sclerosis. Some of these therapies are showing a high level of efficacy, with an acceptable adverse effect profile. Because present therapies have significant limitations in slowing disease progression, require injections, are sometimes associated with significant side effects of immunosuppression, and do little to reverse disability, identifying more effective treatments is an important goal for clinical research in multiple sclerosis. However, in order to improve our current approach to disease-modifying therapies, it is imperative to promote the development of individualized therapy strategies. PMID- 22096359 TI - Inflammatory cytokines and atrial fibrillation: current and prospective views. AB - Atrial fibrillation (AF) is the most common sustained arrhythmia and a challenging clinical problem encountered in daily clinical practice. There is an increasing body of evidence linking inflammation to a broad spectrum of cardiovascular conditions including AF. Historical evidence supports an association between AF and inflammation and is consistent with the association of AF with inflammatory conditions of the heart, such as myocarditis and pericarditis. AF has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. Increased plasma interleukin (IL)-6, C-reactive protein (CRP), and plasma viscosity support the existence of an inflammatory state among "typical" populations with chronic AF. These indexes of inflammation are related to the prothrombotic state and may be linked to the clinical characteristics of the patients (underlying vascular disease and comorbidities), rather than simply to the presence of AF itself. It has been suggested that inflammation may have a role in the development of atrial arrhythmias after cardiac surgery, and that a genetic predisposition to develop postoperative complications exists. Cytokines can have a prognostic significance; IL-6 levels, CRP, and other cytokines may have prognostic value in AF. Cytokine lowering therapies, statins, angiotensin converting enzyme inhibitors and other anti-inflammatory agents may have a role in the treatment of AF. The present article provides an overview of the evidence linking inflammatory cytokines to AF and their therapeutic and prognostic implications. PMID- 22096360 TI - Prostate cancer cells undergoing ER stress in vitro and in vivo activate transcription of pro-inflammatory cytokines. AB - BACKGROUND: Several micro-environmental and cell-intrinsic stimuli cause tumor cells to undergo endoplasmic reticulum (ER) stress in vivo. The occurrence of an ER stress response has been associated with tumor progression and angiogenesis. Recently, we found that pharmacological induction of ER stress in B lymphoma cells upregulates the transcription of several pro-inflammatory cytokines. RESULTS: Here, we show that transgenic adenocarcinoma of the mouse prostate (TRAMP) C1 murine prostate cancer cells induced to undergo ER stress in vitro activate the transcription of interleukin 6 (IL-6), interleukin 23p19 (IL-23p19), and tumor necrosis factor alpha (TNF-alpha). Furthermore we show that TRAMP C1 tumors growing in vivo spontaneously experience ER stress and that transcription of IL-6, IL-23p19, and TNF-alpha correlates with the in vivo ER stress response. CONCLUSIONS: These results suggest that an ER stress response in prostate cancer cells activates a program of pro-inflammatory cytokine transcription. A possible implication of this finding is that cancer cells may use the ER stress response to modify their microenvironment. PMID- 22096358 TI - Potential of anti-inflammatory treatment for cystic fibrosis lung disease. AB - Cystic fibrosis (CF) is the most common life-shortening genetic disorder in Caucasians. With improved diagnosis and treatment, survival has steadily increased. Unfortunately, the overwhelming majority of patients still die from respiratory failure caused by structural damage resulting from airway obstruction, recurrent infection, and inflammation. Here, we discuss the role of inflammation and the development of anti-inflammatory therapies to treat CF lung disease. The inflammatory host response is the least addressed component of CF airway disease at this time. Current challenges in both preclinical and clinical investigation make the identification of suitable anti-inflammatory drugs more difficult. Despite this, many researchers are making significant progress toward this goal and the CF research community has reason to believe that new therapies will emerge from these efforts. PMID- 22096362 TI - Deletion of PPAR-gamma in immune cells enhances susceptibility to antiglomerular basement membrane disease. AB - Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been shown to be immunoregulatory in autoimmune diseases by inhibiting production of a number of inflammatory mediators. We investigated whether PPAR-gamma gene deletion in hematopoietic cells would alter disease pathogenesis in the antiglomerular basement membrane (anti-GBM) mouse model. PPAR-gamma(+/+) and PPAR-gamma(-/-) mice were immunized with rabbit antimouse GBM antibodies and lipopolysaccharide and evaluated for two weeks. Although both the PPAR-gamma(+/+) and PPAR-gamma(-/-) mice had IgG deposition in the glomerulus and showed proteinuria two weeks after injection, glomerular and tubulointerstitial disease in PPAR-gamma(-/-) mice were significantly more severe compared with the PPAR-gamma(+/+) animals. We observed that the PPAR-gamma(-/-) mice had decreased CD4(+)CD25(+) regulatory T cells and an increased CD8(+):CD4(+) ratio as compared with the PPAR-gamma(+/+) mice, suggesting that PPAR-gamma has a role in the regulation of T cells. Furthermore, plasma interleukin-6 levels were significantly increased in the PPAR-gamma(-/-) mice at two weeks as compared with the PPAR-gamma(+/+) animals. Taken together, these studies show that the lack of PPAR-gamma expression enhances inflammatory renal disease in the anti-GBM antibody-induced glomerulonephritis mouse model and suggests targeting PPAR-gamma may have therapeutic efficacy. PMID- 22096361 TI - The effect of smoking on the symptoms and progression of multiple sclerosis: a review. AB - Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disorder of the central nervous system with characteristic demyelinating lesions and axonal loss. MS accounts for the most common cause of neurological disability in young adults in the Western world. The clinical manifestations and the course of MS are highly variable. The early stage of the disease is usually characterized by attacks of neurological dysfunction with complete or incomplete recovery, however, with time disability accumulates in many patients. MS is believed to result from an interplay between susceptibility genes and environmental factors, one of which is smoking. Smoking, a worldwide epidemic, can be regarded as an important risk factor for MS particularly because of its modifiable nature in the quest to prevent or temper the disease course in MS as well as providing possible insights into MS pathogenesis. There are also reports that smoking may influence the symptoms and disease progression in patients with MS. The purpose of this article is to review the effects of smoking on MS symptoms and progression. We conclude that (1) although there are some early reports on worsening of MS symptoms by smoking, the existing evidence is insufficient to thoroughly assess the effects of smoking on the myriad of MS symptoms and (2) smoking seems to adversely influence disease progression in MS patients. We also discuss the potential biological mechanisms linking smoking and MS. PMID- 22096363 TI - Current and emerging strategies for the treatment of acute pericarditis: a systematic review. AB - Pericarditis is a common disorder that has multiple causes and presents in various primary-care and secondary-care settings. It is diagnosed in 0.1% of all hospital admissions and in 5% of emergency room visits for chest pain. Despite the advance of new diagnostic techniques, pericarditis is most commonly idiopathic, and radiation therapy, cardiac surgery, and percutaneous procedures have become important causes. Pericarditis is frequently benign and self limiting. Nonsteroidal anti-inflammatory agents remain the first-line treatment for uncomplicated cases. Integrated use of new imaging methods facilitates accurate detection and management of complications such as pericardial effusion or constriction. In this article, we perform a systematic review on the etiology, clinical presentation, diagnostic evaluation, and management of acute pericarditis. We summarize current evidence on contemporary and emerging treatment strategies. PMID- 22096365 TI - Low intracellular ATP levels exacerbate carcinogen-induced inflammatory stress response and inhibit in vitro tubulogenesis in human brain endothelial cells. AB - Solid tumor development requires angiogenesis and is correlated to the expression of inflammatory markers through cellular metabolic and energetic adaptation. While high glycolysis rates enable the cancer cell compartment to generate adenosine triphosphate (ATP), very little is known about the impact of low intracellular ATP concentrations within the vascular endothelial cell compartment, which is responsible for tumor angiogenesis. Here, we investigated the effect of 2-deoxy-D-glucose (2-DG), a glucose analog that inhibits glycolysis through intracellular ATP depletion, on human brain microvascular endothelial cell (HBMEC) angiogenic properties. While preformed capillaries remained unaffected, we found that in vitro tubulogenesis was dose-dependently decreased by 2-DG and that this correlated with reduced intracellular ATP levels. Procarcinogenic signaling was induced with phorbol 12-myristate 13-acetate (PMA) and found to trigger the proinflammatory marker cyclooxygenase-2 (COX-2) and endoplasmic reticulum (ER) stress marker GRP78 expression, whose inductions were potentiated when PMA was combined with 2-DG treatment. Inversely, PMA-induced matrix-metalloproteinase-9 (MMP-9) gene expression and protein secretion were abrogated in the presence of 2-DG, and this can be partially explained by reduced nuclear factor-kappaB signaling. Collectively, we provide evidence for an intracellular ATP requirement in order for tubulogenesis to occur, and we link increases in ER stress to inflammation. A better understanding of the metabolic adaptations of the vascular endothelial cells that mediate tumor vascularization will help the development of new drugs and therapies. PMID- 22096366 TI - Immunology of fibrotic lung disease: managing infections whilst preventing autoimmunity? AB - Interstitial lung disease (ILD) and lung fibrosis are characterized by different grades of fibrosis and inflammation. Persistent low-grade inflammation is believed to play a major pathogenic role, leading to an imbalance of cytokines, growth factors, and tissue proteinases. Recruited monocytes and macrophages play a pivotal role through their cytokine expression and possibly differentiation into fibrocytes, pericytes, or myofibroblasts. Atypical bacterial infections can cause ILD, although not usually in the form of usual interstitial pneumonia. On the other hand, bacterial colonization is frequently encountered in patients with chronic fibrotic lung disorders, and patients regularly undergo antibacterial treatment. As demonstrated in patients with diffuse panbronchiolitis and other chronic respiratory disorders, treatment with macrolides can be beneficial. This is partly explained by their antimicrobial effects but, for macrolides, immunomodulatory properties have been identified which might also be beneficial in patients with ILD or lung fibrosis. This article reviews the immunology of lung fibrogenesis and putative implications of macrolides for reinstallation of tolerance. PMID- 22096364 TI - Current and emerging strategies for the treatment and management of systemic lupus erythematosus based on molecular signatures of acute and chronic inflammation. AB - Lupus is a chronic, systemic inflammatory condition in which eicosanoids, cytokines, nitric oxide (NO), a deranged immune system, and genetics play a significant role. Our studies revealed that an imbalance in the pro- and antioxidants and NO and an alteration in the metabolism of essential fatty acids exist in lupus. The current strategy of management includes administration of nonsteroidal anti-inflammatory drugs such as hydroxychloroquine and immunosuppressive drugs such as corticosteroids. Investigational drugs include the following: 1) belimumab, a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator, also known as B-cell-activation factor of the TNF family; 2) stem cell transplantation; 3) rituximab, a chimeric monoclonal antibody against CD20, which is primarily found on the surface of B-cells and can therefore destroy B-cells; and 4) IL-27, which has potent anti-inflammatory actions. Our studies showed that a regimen of corticosteroids and cyclophosphamide, and methods designed to enhance endothelial NO synthesis and augment antioxidant defenses, led to induction of long-lasting remission of the disease. These results suggest that methods designed to modulate molecular signatures of the disease process and suppress inflammation could be of significant benefit in lupus. Some of these strategies could be vagal nerve stimulation, glucose-insulin infusion, and administration of lipoxins, resolvins, protectins, and nitrolipids by themselves or their stable synthetic analogs that are known to suppress inflammation and help in the resolution and healing of the inflammation-induced damage. These strategies are likely to be useful not only in lupus but also in other conditions, such as rheumatoid arthritis, scleroderma, ischemia-reperfusion injury to the myocardium, ischemic heart disease, and sepsis. PMID- 22096367 TI - Effects of SU5416 and a vascular endothelial growth factor neutralizing antibody on wear debris-induced inflammatory osteolysis in a mouse model. AB - BACKGROUND: The development of highly vascularized and inflammatory periprosthetic tissue characterizes the progress of aseptic loosening, a major complication of joint arthroplasty. Vascular endothelial growth factor (VEGF) is an important cell signaling protein involved in angiogenesis. The purpose of this study was to investigate whether R2/Fc (a VEGF neutralizing antibody) and SU5416 (a VEGF receptor II [Flk-1] inhibitor) could ameliorate particle-induced inflammatory osteolysis in a mouse model. METHODS: Ultrahigh molecular weight polyethylene (UHMWPE) particles were introduced into established air pouches in BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. Drug treatment was started 2 weeks after bone implantation, and mice without drug treatment were included as controls. Pouch tissues were harvested 4 weeks after bone implantation for molecular and histological analysis, and implanted bone degradation was analyzed by microcomputed tomography. RESULTS: Exposure to UHMWPE particles induced inflammatory osteolysis, which was associated with increased expression of VEGF/Flt-1 proteins. Treatment with R2/Fc significantly improved UHMWPE particle-induced inflammatory osteolysis, and reduced the expression of VEGF/Flt-1 proteins. However, SU5416 treatment showed no effect on UHMWPE particle-induced inflammatory osteolysis. CONCLUSION: Our findings indicate that VEGF signaling exerts a regulatory effect on the development of UHMWPE-induced inflammatory osteolysis, through its unique Flt-1, rather than Flk-1, receptor located on monocyte/macrophage cell lineages. These data provide a biological rationale for a VEGF/Flt-1-targeted treatment strategy, especially during the early stages of the wear debris-induced inflammatory response. PMID- 22096368 TI - The role of the NLRP3 inflammasome in gout. AB - Gout is an inflammatory arthritis characterized by abrupt self-limiting attacks of inflammation caused by precipitation of monosodium urate crystals (MSU) in the joint. Recent studies suggest that orchestration of the MSU-induced inflammatory response is dependent on the proinflammatory cytokine IL-1beta, underlined by promising results in early IL-1 inhibitor trials in gout patients. This IL-1 dependent innate inflammatory phenotype, which is observed in a number of diseases in addition to gout, is now understood to rely on the formation of the macromolecular NLRP3 inflammasome complex in response to the MSU 'danger signal'. This review focuses on our current understanding of the NLRP3 inflammasome and its critical role in MSU-crystal induced inflammatory gout attacks. It also discusses the management of treatment-resistant acute and chronic tophaceous gout with IL-1 inhibitors; early clinical studies of rilonacept (IL-1 Trap), canakinumab (monoclonal anti-IL-1beta antibody), and anakinra have all demonstrated treatment efficacy in such patients. PMID- 22096369 TI - Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers. AB - BACKGROUND: Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils. METHODS: We measured the levels of leptin, tumor necrosis factor alpha (TNF-alpha) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry. RESULTS: In plasma of COPD patients, leptin was inversely correlated with TNF-alpha and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-alpha. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-alpha were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers. CONCLUSION: Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin receptor pathway in the regulation of host defense after smoking cessation. PMID- 22096370 TI - The effect of disease activity on body composition and resting energy expenditure in patients with rheumatoid arthritis. AB - INTRODUCTION: Cachexia is associated with rheumatoid arthritis (RA), but whether it is attributable primarily to reduced dietary intake or increased metabolism is unclear, as is the association with inflammation. To examine whether rheumatoid cachexia is related to increased energy expenditure, reduced food intake, or an inflammatory cytokine response we undertook a prospective, longitudinal study of patients with RA, during periods of relative relapse and remission of inflammation. METHODS: Sixteen patients admitted to hospital with a flare of RA were assessed clinically to determine disease activity and were re-examined 6 weeks later. Their fat-free mass (FFM), dietary intake, resting energy expenditure (REE), and plasma concentrations of interleukin-6 (IL-6) were also measured. Data were compared with those from 16 healthy, age- and sex-matched controls. RESULTS: At baseline the body weight, body mass index, and FFM of patients with RA were significantly lower than those of controls. Disease activity scores of patients (6.39 +/- 0.8) were reduced when the patients were re examined 6 weeks later (5.23 +/- 1.26) and FFM was no longer statistically different from that of controls (visit 1 = 25.8 +/- 10.1 and visit 2 = 26.8 +/- 9.5 versus controls = 32.3 +/- 10.9). There were no differences in food intake between patients and controls or between patients studied at the 2 time points, but REE was greater in patients after correcting for FMM (visit 1 = 62.2 +/- 24.7, visit 2 = 59.7 +/- 26.3 versus controls = 46.0 +/- 13.7). Plasma IL-6 concentrations were significantly higher in patients than controls. Although IL-6 was not significantly correlated with REE, lower REE measurements were not observed when the plasma IL-6 concentration increased. CONCLUSION: Reduced FFM in patients with RA is not attributable to reduced food intake. Energy expenditure is greater in patients when corrected for FFM, particularly in patients with acute flares of disease activity. Although clearly not the only factor involved, increased production of IL-6 may contribute to increasing REE. PMID- 22096372 TI - Apolipoprotein A-I and A-I mimetic peptides: a role in atherosclerosis. AB - Cardiovascular disease remains a major cause of morbidity and mortality in the westernized world. Atherosclerosis is the underlying cause of most cardiovascular diseases. Atherosclerosis is a slowly evolving chronic inflammatory disorder involving the intima of large and medium sized arteries that is initiated in response to high plasma lipid levels, especially LDL. Cells of both the innate and adaptive immunity are involved in this chronic inflammation. Although high plasma LDL levels are a major contributor to most stages of the evolution of atherosclerosis, HDL and its major protein apoA-I possess properties that attenuate and may even reverse atherosclerosis. Two major functions are the ability to induce the efflux of cholesterol from cells, particularly lipid-loaded macrophages, in the artery wall for transfer to the liver, a process referred to as reverse cholesterol transport, and the ability to attenuate the pro inflammatory properties of LDL. The removal of cellular cholesterol from lipid loaded macrophages may also be anti-inflammatory. One of the most promising therapies to enhance the anti-atherogenic, anti-inflammatory properties of HDL is apoA-I mimetic peptides. Several of these peptides have been shown to promote cellular cholesterol efflux, attenuate the production of pro-inflammatory cytokines by macrophages, and to attenuate the pro-inflammatory properties of LDL. This latter effect may be related to their high affinity for oxidized lipids present in LDL. This review discusses the functional properties of the peptides and their effect on experimental atherosclerosis and the results of initial clinical studies in humans. PMID- 22096373 TI - Cyclophilin A cooperates with MIP-2 to augment neutrophil migration. AB - BACKGROUND: Chemokines contribute to inflammatory responses by inducing leukocyte migration and extravasation. In addition, chemoattractants other than classical chemokines can also be present. Many chemokines have been demonstrated to cooperate, leading to an augmentation in leukocyte recruitment and providing a potential role for the presence of multiple chemoattractants. Extracellular cyclophilins are a group of alternative chemotactic factors, which can be highly elevated during various inflammatory responses and, as we have previously shown, can contribute significantly to neutrophil recruitment in an animal model of acute lung inflammation. In the current studies we investigated whether the most abundant extracellular cyclophilin, CypA, has the capacity to function in partnership with 2 classical chemokines known to be secreted in the same model, macrophage inflammatory protein (MIP)-2/CXCL2 and keratinocyte chemoattractant (KC)/CXCL1. METHODS: Neutrophil migration in response to combinations of CypA and MIP-2 or CypA and KC was measured by in vitro chemotaxis assays. Biochemical responses of neutrophils incubated with the combinations of chemoattractants were determined by changes in chemokine receptor internalization and actin polymerization measured by flow cytometry, and changes in intracellular calcium mobilization measured with a calcium sensitive fluorochrome. RESULTS: A combination of CypA and MIP-2, but not KC, augmented neutrophil migration. Based on the level of augmentation, the cooperation between CypA and MIP-2 appeared to be synergistic. Evidence that CypA and MIP-2 cooperate at the biochemical level was demonstrated by increases in receptor internalization, calcium mobilization, and actin polymerization. CONCLUSION: These findings provide evidence for the capacity of extracellular cyclophilins to interact with classical chemokines, resulting in greater and more efficient leukocyte recruitment. PMID- 22096371 TI - Role of the transient receptor potential vanilloid 1 in inflammation and sepsis. AB - The transient receptor potential vanilloid 1 (TRPV1) is a thermoreceptor that responds to noxious temperatures, as well as to chemical agonists, such as vanilloids and protons. In addition, its channel activity is notably potentiated by proinflammatory mediators released upon tissue damage. The TRPV1 contribution to sensory neuron sensitization by proalgesic agents has signaled this receptor as a prime target for analgesic and anti-inflammatory drug intervention. However, TRPV1 antagonists have notably failed in clinical and preclinical studies because of their unwanted side effects. Recent reports have unveiled previously unrecognized anti-inflammatory and protective functions of TRPV1 in several diseases. For instance, this channel has been suggested to play an anti inflammatory role in sepsis. Therefore, the use of potent TRPV1 antagonists as a general strategy to treat inflammation must be cautiously considered, given the deleterious effects that may arise from inhibiting the population of channels that have a protective function. The use of TRPV1 antagonists may be limited to treating those pathologies where enhanced receptor activity contributes to the inflamed state. Alternatively, therapeutic paradigms, such as reduction of inflammatory-mediated increase of receptor expression in the cell surface, may be a better strategy to prevent abrogation of the TRPV1 subpopulation involved in anti-inflammatory and protective processes. PMID- 22096375 TI - Inflammatory cytokines regulate endothelial cell survival and tissue repair functions via NF-kappaB signaling. AB - Inflammation contributes to the development of fibrotic and malignant diseases. We assessed the ability of inflammatory cytokines to modulate endothelial cell survival and functions related to tissue repair/remodeling. Treatment with interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha (2 ng/mL) led to human pulmonary artery endothelial cells becoming spindle-shaped fibroblast-like cells. However, immunoblot and DNA microarray showed no change in most endothelial and mesenchymal markers. In the presence of IL-1beta or TNF-alpha, cells were resistant to apoptosis induced by deprivation of serum and growth factor, and were more migratory. In addition, cells treated with IL-1beta or TNF alpha contracted collagen gels more robustly. In contrast, transforming growth factor-beta1 did not induce these responses. RNA interference targeting nuclear factor (NF)-kappaB p65 blocked the effects of IL-1beta or TNF-alpha on cell morphologic change, survival, migration, and collagen gel contraction. These results suggest that endothelial cells may contribute to tissue repair/remodeling via the NF-kappaB signaling in a milieu of airway inflammation. PMID- 22096376 TI - Profile of darunavir in the management of treatment-experienced HIV patients. AB - Darunavir (formerly TMC114) is a second-generation, sulfonamide-based, peptidomimetic protease inhibitor (PI) with a modified 3-dimensional structure enabling more efficient binding to HIV protease. It has become an important drug, in combination with low-dose ritonavir boosting, in the treatment of both antiretroviral-naive and multiclass-experienced patients. Growing data now exist suggesting it possesses a high barrier to resistance and requires multiple PI mutations in order to suffer reduced virological potency. PMID- 22096377 TI - Role of darunavir in the management of HIV infection. AB - There is an ongoing need for potent antiretroviral therapies to deal with the increasing pool of treatment-experienced patients with multiple drug resistance. The last few years have seen the arrival of 2 new and very potent protease inhibitors - darunavir and tipranavir - alongside 2 whole new classes of anti-HIV agents - the integrase inhibitors and chemokine receptor CCR5 antagonists. This review focuses on the role of darunavir in managing HIV infection, with an emphasis on darunavir's exceptional resistance profile and related clinical effectiveness, pharmacokinetics, tolerability and toxicity data. Darunavir in combination with the pharmacokinetic booster ritonavir has proved to be very effective in the treatment of highly treatment-experienced HIV patients with multiple drug resistance. The favorable tolerability and toxicity profile alongside the drug's high genetic barrier to the development of resistance prompted approval of darunavir for HIV-treatment naive patients. Furthermore, the paradigm of treating HIV with a combination of anti-HIV agents is currently being challenged by ongoing darunavir monotherapy trials and these preliminary data will be discussed. PMID- 22096374 TI - Vascular involvement in systemic sclerosis (scleroderma). AB - Systemic sclerosis (SSc) is an acquired multiorgan connective tissue disease with variable mortality and morbidity dictated by clinical subset type. The etiology of the basic disease and pathogenesis of the systemic autoimmunity, fibrosis, and fibroproliferative vasculopathy are unknown and debated. In this review, the spectrum of vascular abnormalities and the options currently available to treat the vascular manifestations of SSc are discussed. Also discussed is how the hallmark pathologies (ie, how autoimmunity, vasculopathy, and fibrosis of the disease) might be effected and interconnected with modulatory input from lysophospholipids, sphingosine 1-phosphate, and lysophosphatidic acid. PMID- 22096379 TI - The prevalence of human immunodeficiency virus infection among TB patients in Port Harcourt Nigeria. AB - The joint statement by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America recommends that all patients with tuberculosis (TB) undergo testing for human immunodeficiency virus (HIV) infection after counseling. In this study, we investigated the prevalence of HIV infection among 120 patients diagnosed with microbiologically proven TB aged 18 to 54 years with a mean age of 39.5 years (standard deviation 6.75). The subjects studied were 36 male (30%) and 84 females (70%). Enzyme-linked immunosorbent assay methods were used to screen for HIV infection among the subjects. Of the 120 TB patients tested 30 (25%) were positive for HIV infection. The prevalence of HIV was higher in females 24 (80%) compared to males 6 (20%) and among singles (66.7%) compared to married subjects (33.3%) (chi(2) = 83.5 and chi(2) = 126.2, respectively P = 0.001). HIV-1 was the predominant viral subtype. HIV prevalence was significantly higher in subjects in the 38-47 year and 28-37 year age groups (both 40%) followed by the 18-28 year age group (20%) (chi(2) = 42.6, P = 0.05). The mean CD4 lymphocyte count of the HIV-infected TB subjects was significantly lower (195 +/- 40.5 cells/MUL) compared to the non-HIV infected (288 +/- 35.25 cells/MUL P = 0.01). This study has shown a high prevalence of HIV among TB patients. Reactivation of TB among people living with HIV can be reduced by TB preventive therapy and by universal access to antiretroviral therapy. PMID- 22096378 TI - Pharmacologic and nonpharmacologic options for the management of HIV infection during pregnancy. AB - Over the past decade, significant advances have been made in the treatment of HIV 1 infection using both pharmacologic and nonpharmacologic strategies to prevent mother-to-child transmission (MTCT). Optimal prevention of the MTCT of HIV requires antiretroviral drugs (ARV) during pregnancy, during labor, and to the infant. ARVs reduce viral replication, lowering maternal plasma viral load and thus the likelihood of MTCT. Postexposure prophylaxis of ARV agents in newborns protect against infection following potential exposure to maternal HIV during birth. In general, the choice of an ARV for treatment of HIV-infected women during pregnancy is complicated by the need to consider the effectiveness of the therapy for the maternal disease as well as the teratogenic or teratotoxic potential of these drugs. Clinicians managing HIV in pregnancy need to discuss the potential risks and benefits of available therapy options so that mothers can make informed decisions in choosing the best treatment regimen for themselves and for their children. PMID- 22096380 TI - Ethanol suppression of peripheral blood mononuclear cell trafficking across brain endothelial cells in immunodeficiency virus infection. AB - Earlier studies suggested that the combination of alcohol use and immunodeficiency virus infection resulted in more severe neurologic disease than either condition individually. These deleterious interactions could be due to increased immune cell and virus trafficking or may result from interactions between ethanol and human immunodeficiency virus (HIV)-associated toxicity within the brain. To determine the extent to which increased trafficking played a role, we examined the effect of ethanol on the migration of different peripheral blood mononuclear cell (PBMCs) subsets across a brain endothelial cell monolayer. We utilized combinations of feline brain endothelial cells with astrocytes, and/or microglia with either acute exposure to 0.08 g/dL ethanol, a combination of ethanol and feline immunodeficiency virus (FIV), or FIV alone. Adherence of PBMCs to endothelium was increased in all combinations of cells with the addition of ethanol. Despite increased PBMC adhesion with ethanol treatment, transmigration of B cells, monocytes, CD4 T cells and CD8 T cells was not increased and was actually decreased in the presence of astrocytes. Expression of three common adhesion molecules, intercellular adhesion molecule-1 (ICAM1), ICAM2, and vascular cell adhesion molecule, was unchanged or slightly decreased by ethanol. This indicated that although adherence is increased by ethanol it is not due to an increased expression of adhesion molecules. RANTES, MIP1alpha, MIP1beta, and MCP-1 mRNA expression was also studied in brain endothelial cells, astrocytes and microglia by reverse transcriptase-polymerase chain reaction. Ethanol treatment of astrocytes resulted in modest changes of message while FIV caused 7-92-fold increases. The combination of ethanol and FIV reversed the large increase in RANTES and MIP1alpha message in astrocytes but increased MIP1beta and MCP to 20 38-fold over control cells. Thus, modest concentrations of alcohol do not directly influence immune cell trafficking at the endothelium but may exert more complex effects on chemokine expression from astrocytes when combined with FIV. PMID- 22096381 TI - Effect of once-daily FDC treatment era on initiation of cART. AB - OBJECTIVES: Combination antiretroviral therapy (cART) is associated with increased survival among HIV-infected persons. Yet, no research to date has examined whether introduction of once-daily fixed-dosed combinations (FDC) affects the likelihood of cART initiation. We aimed to determine whether implementation of once-daily FDC regimens was associated with changes to cART initiation. We also identified clinical, treatment regimen, and provider characteristics possibly associated with cART initiation. STUDY DESIGN: Retrospective observational analysis. METHODS: We queried electronic medical records between July 1999-June 2006 to identify incident cases of detectable HIV infection in antiretroviral-naive adults. Cox regression with time-dependent covariates was used to examine the effects of once-daily FDC era, clinical, provider, and treatment regimen characteristics on cART initiation. RESULTS: Once daily FDC availability did not change the likelihood of cART initiation, but other characteristics were associated with an increased likelihood: AIDS diagnosis, above-median daily pill consumption, and 16+ yrs of physician HIV experience. Decreased likelihood of cART initiation was associated with CD4 201 350 cells/MUL, HIV RNA < 100,000 copies/mL, and with CD4 > 350 cells/MUL (any HIV RNA level), compared to CD4 <= 200 cells/MUL. CONCLUSION: Availability of once daily FDC-based regimens did not affect likelihood of cART initiation. Patient clinical characteristics appear to be more important predictors of cART initiation. PMID- 22096382 TI - Is it safe? Talking to teens with HIV/AIDS about death and dying: a 3-month evaluation of Family Centered Advance Care (FACE) planning - anxiety, depression, quality of life. AB - PURPOSE: To determine the safety of engaging HIV-positive (HIV+) adolescents in a Family Centered Advance Care (FACE) planning intervention. PATIENTS AND METHODS: We conducted a 2-armed, randomized controlled clinical trial in 2 hospital-based outpatient clinics from 2006-2008 with HIV+ adolescents and their surrogates (n = 76). Three 60-90 minutes sessions were conducted weekly. FACE intervention groups received: Lyon FCACP Survey((c)), the Respecting Choices((r)) interview, and completion of The Five Wishes((c)). The Healthy Living Control (HLC) received: Developmental History, Healthy Tips, Future Planning (vocational, school or vocational rehabilitation). Three-month post-intervention outcomes were: completion of advance directive (Five Wishes((c))); psychological adjustment (Beck Depression, Anxiety Inventories); quality of life (PedsQL(TM)); and HIV symptoms (General Health Self-Assessment). RESULTS: Adolescents had a mean age, 16 years; 40% male; 92% African-American; 68% with perinatally acquired HIV, 29% had AIDS diagnosis. FACE participants completed advance directives more than controls, using time matched comparison (P < 0.001). Neither anxiety, nor depression, increased at clinically or statistically significant levels post intervention. FACE adolescents maintained quality of life. FACE families perceived their adolescents as worsening in their school (P = 0.018) and emotional (P = 0.029) quality of life at 3 months, compared with controls. CONCLUSIONS: Participating in advance care planning did not unduly distress HIV+ adolescents. PMID- 22096383 TI - Novel mechanisms of central nervous system damage in HIV infection. AB - Human immunodeficiency virus-1 infection of the central nervous system is an early event after primary infection, resulting in motor and cognitive defects in a significant number of individuals despite successful antiretroviral therapy. The pathology of the infected brain is characterized by enhanced leukocyte infiltration, microglial activation and nodules, aberrant expression of inflammatory factors, neuronal dysregulation and loss, and blood-brain barrier disruption. Months to years following the primary infection, these central nervous system insults result in a spectrum of motor and cognitive dysfunction, ranging from mild impairment to frank dementia. The mechanisms that mediate impairment are still not fully defined. In this review we discuss the cellular and molecular mechanisms that facilitate impairment and new data that implicate intercellular communication systems, gap junctions and tunneling nanotubes, as mediators of human immunodeficiency virus-1 toxicity and infection within the central nervous system. These data suggest potential targets for novel therapeutics. PMID- 22096384 TI - Optimizing management of treatment-naive and treatment-experienced HIV+ patients: the role of maraviroc. AB - Maraviroc is the first CCR5 antagonist approved for the treatment of HIV-1 infection. It specifically inhibits the replication of R5 viruses by blocking viral entry. HIV-1 tropism can be estimated accurately and predict viral response to maraviroc. Genotypic tools are increasingly replacing phenotypic assays in most places. The favorable pharmacokinetic properties and the good safety profile of maraviroc may support an earlier use of the drug in HIV-1 infection, as well as favor its consideration as part of switch strategies in patients under suppressive antiret-roviral regimens containing less-well-tolerated drugs. Moreover, a particular immune benefit of maraviroc might encourage its use as part of intensification strategies in HIV-infected patients with impaired CD4 gains despite prolonged suppression of HIV replication with antiretroviral therapy. However, the long-term consequences of using maraviroc must be carefully checked, given its particular mechanism of action, blocking a physiologic cell receptor. PMID- 22096385 TI - Novel strategies in the use of lopinavir/ritonavir for the treatment of HIV infection in children. AB - Lopinavir/ritonavir (LPV/r) is considered by many as the first choice protease inhibitor (PI) for children. This co-formulation avoids the need for children to take ritonavir separately to "boost" the levels of lopinavir. LPV/r has high virologic potency, an excellent toxicity profile and a high barrier to the development of viral resistance. However, LPV/r has poor tolerability of the oral suspension (due to the poor taste of ritonavir), difficult dosing requirements and metabolic side effects, especially hyperlipidemia. The new tablet low-dose formulation (100/25 mg) may allow more convenient antiretroviral treatment in children. Novel strategies of LPV/r in childhood could maximize its advantages. For example, infants infected with HIV despite single dose Nevirapine after birth need effective combination antiretroviral treatment. This can be given using a higher dose of LPV/r with therapeutic drug monitoring. Other novel uses include once daily LPV/r regimens in older children and adolescents and lower doses of LPV/r in certain populations, which may decrease hyperlipidemia. Heavily pre treated children might benefit from a double PI/r regimen which includes LPV/r. The high potency of LPV/r needs to be balanced with convenient regimens, to enhance adherence and decrease toxicity whenever possible. The aim of this review is to discuss the rationale behind these novel strategies of LPV/r use in pediatric antiretroviral treatment as well as their results and limitations. PMID- 22096386 TI - Adherence to antiretroviral therapy in Nigeria: an overview of research studies and implications for policy and practice. AB - Both Human Immunodeficiency Virus (HIV) infection and AIDS remain major public health crises in Nigeria, a country which harbors more people living with HIV/AIDS than any country in the world, with the exception of South Africa and India. In response to the HIV pandemic, global and international health initiatives have targeted several countries, including Nigeria, for the expansion of antiretroviral therapy (ART) programs for the increasing number of affected patients. The success of these expanded ART initiatives depends on the treated individual's continual adherence to antiretroviral (ARV) drugs. Thirteen peer reviewed studies concerning adherence to ART in Nigeria were reviewed with very few pediatric and adolescent studies being found. Methodologies of adherence measurement were analyzed and reasons for nonadherence were identified in the geopolitical zones in the federal republic of Nigeria. The results of the literature review indicate that adherence to ART is mixed (both high and low adherence) with patient self-recall identified as the common method of assessment. The most common reasons identified for patient nonadherence include the cost of therapy (even when the drugs are heavily subsidized), medication side effects, nonavailability of ARV drugs, and the stigma of taking the drugs. This manuscript highlights the policy and practice implications from these studies and provides recommendations for future ART program management. PMID- 22096387 TI - Predictors of frequency of condom use and attitudes among sexually active female military personnel in Nigeria. AB - BACKGROUND: Despite awareness of condom efficacy, in protecting against both human immunodeficiency virus/sexually transmitted diseases (HIV/STDs) and unintended pregnancy; some females find it difficult to use or permit condom use consistently because of the power imbalances or other dynamics operating in their relationships with males. The purpose of this study was to determine the factors that predict the frequency of condom use and attitudes among sexually active female military personnel in Nigeria. METHODS: This study used a cross-sectional design in which a total of 346 responses were obtained from consenting female military personnel in two cantonments in Southwestern Nigeria between 2006 and 2008. The study instrument was designed to assess HIV/acquired immunodeficiency syndrome (AIDS) knowledge (HAK), HIV risk behaviors (HRB), alcohol and drug use, condom attitudes and barriers (CAS) condom use self-efficacy (CUS) and social support to condom use (SSC). The sociodemographic characteristics of participants were also captured. Univariate analysis and multivariable logistic regression were used for modeling the predictors of condom use. RESULTS: The results showed that 63% of the respondents reported using condoms always, 26% sometimes used condoms and 11% never used condoms during a sexual encounter in the past three months. Univariate analysis revealed that significant associations existed between CAB (P < 0.05), HRB (P < 0.01) and SSC (P < 0.01) with the frequency of condom use. The following sociodemographic variables: age, marital status, number of children, employment status and type of sexual relationship were also significantly (P <= 0.05) associated with consistent condom use in the study group. Multivariate analysis indicated that marital status, type of relationship and CAB were the only significant predictors (r(2) = 0.37; P <= 0.05) of condom use behaviors after adjusting for all other factors in the model. CONCLUSIONS: Findings indicate that consistent condom use could be enhanced through gender specific intervention programs that incorporate the predictor variables identified. These are likely to be successful in decreasing sexual risk behaviors in the subpopulation. PMID- 22096388 TI - Optimal management of oropharyngeal and esophageal candidiasis in patients living with HIV infection. AB - Mucocutaneous candidiasis is frequently one of the first signs of human immunodeficiency virus (HIV) infection. Over 90% of patients with AIDS will develop oropharyngeal candidiasis (OPC) at some time during their illness. Although numerous antifungal agents are available, azoles, both topical (clotrimazole) and systemic (fluconazole, itraconazole, voriconazole, posaconazole) have replaced older topical antifungals (gentian violet and nystatin) in the management of oropharyngeal candidiasis in these patients. The systemic azoles, are generally safe and effective agents in HIV-infected patients with oropharyngeal candidiasis. A constant concern in these patients is relapse, which is dependent on the degree of immunosuppression commonly seen after topical therapy, rather than with systemic azole therapy. Candida esophagitis (CE) is also an important concern since it occurs in more than 10% of patients with AIDS and can lead to a decrease in oral intake and associated weight loss. Fluconazole has become the most widely used antifungal in the management of mucosal candidiasis. However, itraconazole and posaconazole have similar clinical response rates as fluconazole and are also effective alternative agents. In patients with fluconazole-refractory mucosal candidiasis, treatment options now include itraconazole solution, voriconazole, posaconazole, and the newer echinocandins (caspofungin, micafungin, and anidulafungin). PMID- 22096390 TI - Management of Pneumocystis Jirovecii pneumonia in HIV infected patients: current options, challenges and future directions. AB - The discovery of the Human Immunodeficiency Virus (HIV) was led by the merge of clustered cases of Pneumocystis jirovecii Pneumonia (PCP) in otherwise healthy people in the early 80's.1,2 In the face of sophisticated treatment now available for HIV infection, life expectancy approaches normal limits. It has dramatically changed the natural course of HIV from a nearly fatal infection to a chronic disease.3-5 However, PCP still remains a relatively common presentation of uncontrolled HIV. Despite the knowledge and advances gained in the prevention and management of PCP infection, it continues to have high morbidity and mortality rates. Trimethoprim-sulfamethoxazole (TMP-SMZ) remains as the recommended first line treatment. Alternatives include pentamidine, dapsone plus trimethoprim, clindamycin administered with primaquine, and atovaquone. For optimal management, clinicians need to be familiar with the advantages and disadvantages of the available drugs. The parameters used to classify severity of infection are also important, as it is well known that the adjunctive use of steroids in moderate to severe cases have been shown to significantly improve outcome. Evolving management practices, such as the successful institution of early antiretroviral therapy, may further enhance overall survival rates. PMID- 22096391 TI - An update on the use of Atripla in the treatment of HIV in the United States. AB - Atripla((r)) (Gilead Sciences Inc, Foster City, CA, USA and Bristol-Myers Squibb, New York City, NY, USA) is a coformulated single pill composed of efavirenz, emtricitabine, and tenofovir disoproxil, intended as a once-daily potent combination antiretroviral therapeutic agent. Its efficacy is equivalent to the 3 component drugs taken in a combination as single medications. The coformulated antiretroviral regimen can be quite effective in patients whose human immunodeficiency virus is sensitive to all 3 components of Atripla. However, women at risk of pregnancy, already pregnant, or nursing mothers should not take Atripla, due to the teratogenic potential of the efavirenz moiety. Adverse effects are similar to those seen with the constituent medications, including potential central nervous system effects and renal toxicity. Since its US Food and Drug administration approval, prescriptions for Atripla have increased steadily. PMID- 22096389 TI - HIV reservoirs in vivo and new strategies for possible eradication of HIV from the reservoir sites. AB - Even though the treatment of human immunodeficiency virus (HIV)-infected individuals with highly active antiretroviral therapy (HAART) provides a complete control of plasma viremia to below detectable levels (<40 copies/mL plasma), there is an unequal distribution of all antiretroviral drugs across diverse cellular and anatomic compartments in vivo. The main consequence of this is the acquisition of resistance by HIV to all known classes of currently prescribed antiretroviral drugs and the establishment of HIV reservoirs in vivo. HIV has a distinct advantage of surviving in the host via both pre-and postintegration latency. The postintegration latency is caused by inert and metabolically inactive provirus, which cannot be accessed either by the immune system or the therapeutics. This integrated provirus provides HIV with a safe haven in the host where it is incessantly challenged by its immune selection pressure and also by HAART. Thus, the provirus is one of the strategies for viral concealment in the host and the provirus can be rekindled, through unknown stimuli, to create progeny for productive infection of the host. Thus, the reservoir establishment remains the biggest impediment to HIV eradication from the host. This review provides an overview of HIV reservoir sites and discusses both the virtues and problems associated with therapies/strategies targeting these reservoir sites in vivo. PMID- 22096392 TI - Role of etravirine in the management of treatment-experienced patients with human immunodeficiency virus type 1. AB - Etravirine is an oral diarylpyrimidine compound, a second-generation human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI) with expanded antiviral activity against NNRTI-resistant HIV-1, to be used in combination therapy for treatment-experienced patients. Compared with first-generation NNRTIs, etravirine has a high genetic barrier to resistance, and is better tolerated without the neuropsychiatric and hepatic side effects of efavirenz and nevirapine, respectively. Its safety profile is comparable to placebo with the exception of rash, which has been mild and self limited in the great majority of patients. In phase III clinical trials among treatment-experienced patients harboring NNRTI-resistant HIV-1, etravirine in combination with an optimized background regimen (OBR) that included ritonavir boosted darunavir demonstrated superior antiviral activity than the control OBR. In addition, patients on the etravirine arm had fewer AIDS-defining conditions, hospitalizations, and lower mortality compared with the OBR control arm. PMID- 22096393 TI - Profile of maraviroc: a CCR5 antagonist in the management of treatment experienced HIV patients. AB - Maraviroc is the first and, so far, the only licensed representative of the class of chemokine receptor type 5 (CCR5) inhibitors used for the treatment of human immunodeficiency virus (HIV) infection. Its safety and efficacy were demonstrated in several clinical trials, and its use was approved in 2007 by the responsible authorities. Some specific issues are correlated with maraviroc and its use. It is the only drug in the antiretroviral armamentarium, which does not interact with the viral enzymes but with a human receptor. Hence, it is able to be long term effective only if the infecting virus uses, exclusively, the CCR5 receptor. Occurrence and detection of the CCR5 tropism are some of the great challenges of maraviroc use in treatment-experienced patients. Although up to 80% of naive patients harbor CCR5-tropic virus, the occurrence of CXCR4 or other tropisms increases with the duration of HIV infection and treatment. Nonetheless, maraviroc is a potent medication for eligible patients and helps to improve the outcome of antiretroviral treatment (ART) of HIV infection. PMID- 22096394 TI - Long-term treatment of patients with HIV-1: the role of atazanavir. AB - BACKGROUND: The introduction of highly-active antiretroviral therapy (HAART) remains a major milestone in the management of HIV-infected patients. Protease inhibitors (PI) are commonly used as part of triple combinations, given that to antiviral potency, better tolerance and convenience has been achieved in recent years. OBJECTIVE: To summarize and update evidence-based information about atazanavir (ATV) on initial, simplification, and rescue interventions in HIV patients. METHODS: Review of observational and randomized trials reported in medical conferences, peer-reviewed journals, and treatment guidelines. RESULTS: ATV is a second-generation PI, which has shown across studies potent antiviral activity and high genetic barrier, both in HAART-naive patients or after virological failure. Indulgent metabolic profile, in terms of insulin glucose and lipid levels, adds value to this drug for the long-term management of HIV infection. PMID- 22096396 TI - Human immunodeficiency virus prevalence in an unbooked obstetric population in the Niger Delta. AB - Despite recent advances in the prevention of transmission of human immunodeficiency virus (HIV) infection from mother to child during pregnancy, infants continue to be born and infected with HIV, particularly in Africa. This study was undertaken to determine the seroprevalence of HIV infection among unbooked pregnant women in the Niger Delta of Nigeria. One hundred and eighteen consecutively recruited unbooked subjects presenting to the isolation ward at the University of Port Harcourt Teaching Hospital were screened for HIV. Among the 118 subjects studied, 30 (25.4%) were positive for HIV. HIV-1 was the predominant viral strain. Gestational age of subjects at presentation was 28-40 weeks and mean age was 35.04 +/- 8.06 years. The majority of subjects were primigravidas 66 (55.9%), while 52 (44.1%) were multigravidas. The prevalence of HIV was significantly higher among unbooked pregnant women with less formal education: 14 (11.9%) compared with 9 (7.6%), 5 (4.2%), and 2 (1.7%) for those with primary, secondary, and tertiary education, respectively (P = 0.01). Among the occupational groups, the prevalence of HIV was significantly higher among traders 14 (11.9%) than in career women 5 (4.2%, P = 0.04). Multigravid women were more susceptible to HIV infection 17 (14.4%) than primigravid women. Perinatal mortality and emergency cesarean section was high among unbooked pregnant women. The prevalence of HIV observed amongst unbooked antenatal subjects in this study is significantly higher than those of booked patients in previous studies. These findings are very pertinent to health care delivery, because this pool of unbooked patients may not be benefiting from the Prevention of Maternal to Child Transmission program, thus increasing the pediatric HIV burden in our environment. PMID- 22096397 TI - Effect of HIV infection on time to recovery from an acute manic episode. AB - INTRODUCTION: Understanding factors affecting the time to recovery from acute mania is critical in the management of manic syndromes. The aim of this study was to determine the effect of HIV infection on time to recovery from acute mania. METHODS: We performed a retrospective study in which medical charts of individuals who were treated for acute mania were reviewed. Survival analysis with Cox regression models were used to compare time to recovery from an acute manic episode between human immunodeficiency virus (HIV)-positive individuals and HIV-negative individuals. RESULTS: Median survival time was one week for HIV positive individuals and more than four weeks for HIV-negative individuals (chi(2) = 18.4, P value = 0.000). HIV infection was the only marginally significant independent predictor of survival probability on the acute admission ward (hazards ratio 2.87, P = 0.06). CONCLUSION: Acute mania in HIV-infected persons responds faster to psychotropic drugs compared with that in HIV-negative persons. PMID- 22096395 TI - New and emerging agents in the management of lipodystrophy in HIV-infected patients. AB - Lipodystrophy remains a major long-term complication in human immunodeficiency virus-infected patients under antiretroviral (ARV) therapy. Patients may present with lipoatrophy or lipohypertrophy or both. The choice of treatments to improve fat redistribution depends on the form of lipodystrophy and its duration. Measures known to improve lipoatrophy are switches in ARV therapy (stavudine or zidovudine to abacavir or tenofovir) and filling interventions. Pioglitazone may be added to these measures, although any benefits appear small. Uridine and leptin were found to be disappointing so far. Regarding lipohypertrophy, diet and exercise, recombinant human growth hormone, and metformin may reduce visceral fat, but may worsen subcutaneous lipoatrophy. Surgical therapy may be required. Attractive pharmacologic treatments include growth hormone-releasing factor and leptin. Adiponectin and adiponectin receptors are promising therapeutic targets to explore. PMID- 22096398 TI - The effect of aging, nutrition, and exercise during HIV infection. AB - Medical advances continue to change the face of human immunodeficiency virus- acquired immunodeficiency syndrome (HIV/AIDS). As life expectancy increases, the number of people living with HIV rises, presenting new challenges for the management of a chronic condition. Aging, nutrition, and physical activity can influence outcomes in other chronic conditions, and emerging data show that each of these factors can impact viral replication and the immune system in HIV. HIV infection results in a decline of the immune system through the depletion of CD4+ T cells. From initial infection, viral replication is a continuous phenomenon. Immunosenescence, a hallmark of aging, results in an increased susceptibility to infections secondary to a delayed immune response, and this phenomenon may be increased in HIV-infected patients. Optimal nutrition is an important adjunct in the clinical care of patients with HIV. Nutritional interventions may improve the quality and span of life and symptom management, support the effectiveness of medications, and improve the patient's resistance to infections and other disease complications by altering immunity. Moderate physical activity can improve many immune parameters, reduce the risk of acute infection, and combat metabolic abnormalities. As people with HIV age, alternative therapies such as nutrition and physical activity may complement medical management. PMID- 22096399 TI - Stromal cell-derived factor 1 polymorphism in patients infected with HIV and implications for AIDS progression in Tunisia. AB - BACKGROUND: An interesting finding in the epidemiology of human immunodeficiency virus (HIV) infection is that certain mutations in genes coding for chemokines, and their receptors and ligands, may confer resistance or susceptibility to HIV-1 infection and acquired immunodeficiency syndrome (AIDS) progression. The mutation most frequently studied is stromal cell-derived factor (SDF)1-3'A, a single nucleotide polymorphism in the 3' untranslated region at the 801 position of the SDF1 gene, which seems to be associated with susceptibility or resistance to diseases, including AIDS. We examined the frequency of the above polymorphisms in the Tunisian population, and evaluated their contribution to a protective genetic background against HIV infection and progression. METHODS AND MATERIALS: One hundred forty blood samples from HIV-infected patients from the Cellular Immunology Research Laboratory at the National Blood Transfusion Center were compared with those of 164 random blood donors from the same center. Genotyping was initially performed by polymerase chain reaction (PCR) analysis. SDF1 PCR product genomic regions were further subjected to restriction fragment length polymorphism analysis for genotype determination. Screening for the SDF1 polymorphism in the HIV-infected population yielded 56 heterozygous (40%), 52 mutation homozygous (37.1%), and 32 wild-type homozygous (22.8%) subjects. In contrast, in our healthy population, we found 70/164 heterozygous (42.6%), nine mutation homozygous (5.4%), and 85 wild-type homozygous (51.8%) subjects. The allele frequencies in the HIV-infected and healthy populations were f(SD1 3'A) = 57.1%, f(SDF1) = 42.8%, f(SDF1 3'A) = 26.8%, and f(SDF1) = 73.1%, respectively. The allelic and genotypic frequencies of the SDF1 3'A in our population show significantly higher distribution profiles compared with those observed in other Caucasian, European, and African American populations. Our results were examined by chi(2) test and appear to confirm an association between polymorphism and AIDS progression. A higher odds ratio (>1) was found for the SDF1-3'A allele than for the wild-type allele (<1). CONCLUSION: This result seems to confirm that the SDF1 3'A allele is associated with acceleration and progression from HIV infection to AIDS in the Tunisian population. PMID- 22096400 TI - Atherosclerosis: pathogenesis and increased occurrence in individuals with HIV and Mycobacterium tuberculosis infection. AB - Atherosclerosis is a leading cause of coronary heart disease and stroke. Since 1981, more than 980,000 cases of AIDS have been reported in the United States. According to the Centers for Disease Control, more than 1 million Americans may be infected with HIV. By killing or damaging CD4+ T cells of the body's immune system, HIV progressively destroys the body's ability to fight infections. People diagnosed with AIDS often suffer from life-threatening diseases caused by opportunistic infections such as tuberculosis. HIV-infected individuals have increased risks for atherosclerosis. This review summarizes the effects of oxidized low density lipoproteins in impairing macrophage functions in individuals with atherosclerosis (with and without HIV infection) thereby enhancing the susceptibility to Mycobacterium tuberculosis infection. PMID- 22096401 TI - Management of chronic diarrhea in HIV-infected patients: current treatment options, challenges and future directions. AB - Diarrhea is a common clinical manifestation of HIV infection regardless of whether the patients have AIDS. HIV and malnutrition tend to occur in the same populations, the underprivileged and resource-poor. Malnutrition increases severity and mortality of infection. Occurrence of chronic diarrhea in HIV infected patients, gut status and pathogenic agents, nutritional status and the crucial role of nutrition are reviewed. Bovine colostrum-based food can be useful for managing chronic diarrhea in HIV-infected patients, enhancing both nutritional and immunological status. PMID- 22096402 TI - Impact of comorbidities and drug therapy on development of renal impairment in a predominantly African American and Hispanic HIV clinic population. AB - PURPOSE: Renal impairment in human immunodeficiency virus (HIV)-infected patients could potentially be caused by many factors. HIV-related renal impairment risks have been little studied in African Americans and Hispanics. We investigated the impact of HIV itself, highly active antiretroviral therapy (HAART), comorbidities, and non-HIV-related drug treatment on glomerular filtration rate in a predominantly African American/Hispanic HIV-infected population who had received HAART for at least one year. This study was a retrospective electronic medical record database evaluation of renal impairment risks in a largely African American/Hispanic HIV population obtaining medical care at an HIV clinic in Dallas, Texas. METHODS: Proportional hazards models were used to investigate an association between an estimated glomerular filtration rate decrease >25% from baseline (ie, renal impairment) and demographics, antiretroviral/nonantiretroviral medications, comorbidities (hypertension, diabetes mellitus, hepatitis C virus [HCV] infection, hepatitis B virus [HBV] infection), CD4+ counts, viral load, and duration patients were monitored at the clinic (time on study). RESULTS: In total, 323 patients were evaluated: 82% males; 61% African American/12% Hispanic/19% Caucasian; mean age 37.9 years (standard deviation [SD] 8.5); 6% HBV-positive; 34% HCV-positive; 29% hypertensive; 3% diabetic; 52% tenofovir-treated; mean weight 75.4 kg (SD, 15.4); mean estimated glomerular filtration 114.5 mL/min/1.73 m(2) (SD, 36.7) using the Modification of Diet in Renal Disease (MDRD) calculation method; mean creatinine clearance (from which estimated glomerular filtration was extrapolated) by the Cockcroft-Gault calculation method 120.6 mL/min/1.73 m(2) (SD, 41.2); mean time on study 2.7 years (SD, 1.0 year). An estimated glomerular filtration rate decrease of >25% from baseline was significantly associated with time on study (P = 0.0017; hazards ratio [HR] = 0.999) and hypertension (HR = 1.706; P = 0.0158) by the MDRD method, and with age (HR = 1.039; P = 0.0077), weight (HR = 0.987; P = 0.0023), and time on study (HR = 0.999; P = 0.0043) by extrapolation of Cockcroft-Gault creatinine clearance calculation. No specific HAART agent was associated with significant renal impairment risk by the definition used in this study. CONCLUSION: This retrospective database study showed time on study, hypertension, weight, and age to be the only significant predictors of an estimated glomerular filtration rate decrease >25% from baseline. PMID- 22096403 TI - Antiretroviral therapy initiated soon after HIV diagnosis as standard care: potential to save lives? AB - In 2008, an estimated 33.4 million people were infected with human immunodeficiency virus (HIV) and ~4 million people were receiving antiretroviral therapy (ART). However, in 2007, an estimated 6.7 million people were in need of ART under the current World Health Organization guidelines, and 2.7 million more people became infected with HIV. Most of those not currently eligible for ART will become eligible within the next decade, making the current treatment strategy unsustainable. The development of cheaper, less toxic, and more potent antiretrovirals over the past decade has made it possible to consider novel strategies of arresting the HIV/AIDS epidemic. Evidence is growing that ART can be used to prevent HIV transmission and that earlier initiation of treatment is beneficial for those infected with HIV. A mathematical model predicts that by testing whole communities annually and treating all who are infected immediately, up to 7.2 million AIDS-related deaths could be prevented in the next 40 years, long-term funding required to fight the HIV epidemic could be reduced, and, most importantly, control of the HIV/ AIDS epidemic could be regained within 1-2 years of full-scale implementation of the strategy. We discuss the development of the concept of ART for the prevention of HIV transmission and the modeled impact that a test-and-treat strategy could have on the HIV epidemic, and consequently argue that a field trial should be carried out to confirm model parameters, highlight any practical problems, and test the model's predictions. PMID- 22096405 TI - Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings. AB - The vast majority of people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome reside in the developing world, in settings characterized by limited health budgets, critical shortages of doctors, limited laboratory monitoring, a substantial burden of HIV in children, and high rates of coinfection, in particular tuberculosis. Therefore, the extent to which new antiretrovirals will contribute to improvements in the management of HIV globally will depend to a large extent on their affordability, ease of use, low toxicity profile, availability as pediatric formulations, and compatibility with tuberculosis and other common drugs. We undertook a systematic review of the available evidence regarding drug interactions, and the efficacy and safety of rilpivirine (also known as TMC-278), and assessed our findings in view of the needs and constraints of resource-limited settings. The main pharmacokinetic interactions relevant to HIV management reported to date include reduced bioavailability of rilpivirine when coadministered with rifampicin, rifabutin or acid suppressing agents, and reduced bioavailability of ketoconazole. Potential recommendations for dose adjustment to compensate for these interactions have not been elaborated. Trials comparing rilpivirine and efavirenz found similar outcomes up to 96 weeks in intent-to-treat analysis; failure of rilpivirine was mainly virological, whereas failure among those exposed to efavirenz was mainly related to the occurrence of adverse events. Around half of the patients who fail rilpivirine develop non-nucleoside reverse transcriptase inhibitor resistance mutations. The incidence of Grade 2-4 events was lower for rilpivirine compared with efavirenz. Grade 3-4 adverse events potentially related to the drugs were infrequent and statistically similar for both drugs. No dose-response relationship was observed for efficacy or safety, and the lowest dose (25 mg) was selected for further clinical development. The potential low cost and dose of the active pharmaceutical ingredient means that rilpivirine can potentially be manufactured at a low price. Moreover, its long half-life suggests the potential for monthly dosing via nonoral routes, with promising early results from studies of a long-acting injectable formulation. These characteristics make rilpivirine an attractive drug for resource-limited settings. Future research should assess the potential to improve robustness and assess the clinical significance of interaction with antituberculosis drugs. PMID- 22096404 TI - Antimicrobial therapy for the treatment of opportunistic infections in HIV/AIDS patients: a critical appraisal. AB - The widespread use of antiretroviral therapy (ART) has entirely changed the management of human immunodeficiency virus (HIV) infection and dramatically reduced the rates of opportunistic infections (OI). However, OI continue to cause significant morbidity and mortality in both developed countries, where presentation with advanced HIV infection is common, and also in developing countries where ART is less widely available. Evidence to direct OI guidelines is partly limited by the fact that many large-scale studies date from the pre-ART era and more recent studies are sometimes poorly powered due to the falling rates of OI. Treatment of OI is now known to be as much about antimicrobials as about immune reconstitution with ART, and recent studies help guide the timing of initiation of ART in different infections. OI have also become complicated by the immune reconstitution inflammatory syndrome phenomenon which may occur once successful immune recovery begins. Trimethoprim-sulfamethoxazole has long been one of the most important antibiotics in the treatment and prevention of OI and remains paramount. It has a broad spectrum of activity against Pneumocystis jiroveci, toxoplasmosis, and bacterial infections and has an important role to play in preventing life-threatening OI. New advances in treating OI are coming from a variety of quarters: in cytomegalovirus eye disease, the use of oral rather than intravenous drugs is changing the face of therapy; in cryptococcal meningitis, improved drug formulations and combination therapy is improving clearance rates and reducing drug toxicities; and in gut disease, the possibility of rapid immune restitution with ART is replacing the need for antimicrobials against cryptosporidia and microsporidia. PMID- 22096406 TI - Strategies to improve HIV treatment adherence in developed countries: clinical management at the individual level. AB - REMARKABLE ADVANCES IN THE TREATMENT OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) DISEASE HAVE BEEN BLUNTED BY WIDESPREAD SUBOPTIMAL ADHERENCE (IE, NONADHERENCE), WHICH HAS EMERGED AS A MAJOR BARRIER TO ACHIEVING THE PRIMARY GOAL OF ANTIRETROVIRAL (ARV) THERAPY: suppression of HIV viral load. Nonsuppressed HIV viral load is associated with drug resistance, increased morbidity and mortality, and a higher risk of person-to-person HIV transmission. For HIV-infected individuals who are failing HIV treatment due to nonadherence, becoming adherent is a life-saving behavior change. However, overcoming nonadherence is one of the most daunting challenges in the successful management of HIV disease. The purpose of this paper is to provide clinicians with a better understanding of nonadherence to ARV treatment and to review the various factors that have been associated with either adherence or nonadherence. Strategies are presented that may help the nonadherent individual become ready to take HIV medications as prescribed. PMID- 22096407 TI - Characteristics of foot fractures in HIV-infected patients previously treated with tenofovir versus non-tenofovir-containing highly active antiretroviral therapy. AB - In a retrospective case series study, medical records were evaluated for all male patients infected with human immunodeficiency virus (HIV) diagnosed over a one year period with foot fractures (n = 30) confirmed by magnetic resonance imaging at a Los Angeles outpatient private practice rheumatology clinic. Proportionally more patients had received tenofovir prefracture (17 [57%]) than those who had not (13 [43%]). At fracture diagnosis, these two groups were similar in median age (49 versus 48 years), HIV-1 RNA (both 1.7 log(10) copies/mL), CD4 count (300 versus 364/mm(3)), time between HIV diagnosis and foot fracture (both 17 years), family history of degenerative bone disease (24% versus 23%), prevalence of malabsorption syndrome, renal failure, calcium deficiency, or vitamin D deficiency, and concurrent use of bisphosphonates, calcitonin, and diuretics. However, more tenofovir-treated patients had osteoporosis (35% versus 8%), stress type fractures (53% versus 31%), concurrent fractures (12% versus 0%), wasting syndrome (29% versus 15%), truncal obesity (18% versus 8%), smoked cigarettes (more than one pack/day for more than one year; 35% versus 8%), dual energy X-ray absorptiometry (DEXA) T scores < -2.4 (denoting osteoporosis) at the femur (24% versus 9%) and spine (47% versus 36%), and had received protease inhibitors (71% versus 46%), non-nucleoside reverse transcriptase inhibitors (24% versus 0%), prednisone (24% versus 0%), testosterone (47% versus 23%), and teriparatide (29% versus 8%). Median time from tenofovir initiation until fracture was 2.57 (range 1.17-5.69) years. In conclusion, more foot fractures were observed in tenofovir treated patients than in non-tenofovir-treated patients with HIV infection. Comorbidities and/or coadministered drugs may have been contributory. PMID- 22096408 TI - Participation of women in HIV clinical trials: the IPEC-FIOCRUZ experience. AB - BACKGROUND: Fifty percent of people living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) worldwide are female. In Brazil, for example, 240,000 women are infected with HIV, rates of infection in women have increased over the last two decades, and addressing HIV prevention and treatment for women at risk for, or living with, HIV/AIDS remains a challenge. To better address the needs of women living with HIV in Brazil, the Instituto de Pesquisa Clinica Evandro Chagas - Fundacao Oswaldo Cruz (IPEC-FIOCRUZ) HIV Women's Cohort was established in 1996 to study the natural history of women seeking HIV care. This analysis describes the characteristics of women in the cohort who participated in HIV clinical trials between 1999 and 2008. METHODS: A total of 736 Women's Cohort participants were in active follow-up and 665 participants from the Women's Cohort were included in univariable and multivariable analyses to determine socioeconomic and sociodemographic factors associated with women's participation in HIV clinical trials at our site. RESULTS: Of the complete cohort, 23% participated in a clinical trial between January 1999 and July 2008. Odds of participation decreased for women who were younger than 35 years old, currently employed, had an HIV-positive sexual partner, and/or who reported a lifetime history of illicit drug use. Alternatively, the odds of participation increased for women who had more than 8 years of formal education, were living independently, and/or were married or cohabitating. CONCLUSION: The rate of participation in HIV clinical trials by women in the IPEC-Fiocruz Cohort was similar to other published cohorts, but identification of local risk factors and barriers to participation remains important. Our analysis offers a novel description of the factors associated with participation in HIV clinical trials among women in care at IPEC-FIOCRUZ in Rio de Janeiro, Brazil. PMID- 22096409 TI - Growth hormone and tesamorelin in the management of HIV-associated lipodystrophy. AB - HIV-infected patients on highly active antiretroviral therapy (HAART) develop a complex of body composition changes known, including peripheral fat loss (lipoatrophy) and central fat accumulation (lipohypertrophy). These changes may cause significant patient distress, which could in turn interfere with adherence to antiretroviral therapy. Treatment options - including antiretroviral switch, insulin sensitizers, and surgical approaches - have been associated with limited success and potential complications. The observation that low growth hormone levels are associated with central fat accumulation among HIV patients has led to the development of tesamorelin (a growth hormone releasing hormone analog) for the management of central fat accumulation. Randomized controlled trials have shown that administration of tesamorelin is safe and effective in reducing central fat accumulation among HIV-infected patients. This effect is transient, however, and its association with improved cardiovascular risk remains unclear. PMID- 22096410 TI - Role of raltegravir in the management of HIV-1 infection. AB - The development of multiple agents with potent antiretroviral activity against HIV has ushered in a new age of optimism in the management of patients infected with the virus. However, the viruses' dynamic ability to develop resistance against these agents necessitates the investigation of novel targets for viral suppression. Raltegravir represents a first-in-class agent targeting the HIV integrase enzyme, which is responsible for integration of virally encoded DNA into the host genome. Over the last 5 years, clinical trials data has demonstrated an increasing role for raltegravir in the management of both treatment-experienced and treatment-naive HIV-1-infected patients. This review focuses on the evidence supporting raltegravir's efficacy in an array of clinical settings. Other HIV-1 integrase inhibitors in development are also briefly discussed. PMID- 22096411 TI - HIV-related risk perception among female sex workers in Nigeria. AB - BACKGROUND: Over one-third of sex workers in Nigeria are infected with human immunodeficiency virus (HIV), yet there is a lack of understanding of sex workers' own perception of sexual risk-taking. Applying the theory of cognitive dissonance, this paper examined the personal HIV risk perception of brothel-based sex workers. METHODS: The study is based on 24 focus group discussions held among brothel-based sex workers in four geographically and culturally dispersed cities in Nigeria. RESULTS: It was found that sex workers underestimated their risk of infection and rationalized, defended, or justified their behaviors, a typical psychological response to worry, threat, and anxiety arising from the apparent discrepancies between beliefs and behaviors. To reduce dissonance, many sex workers had a strong belief in fatalism, predestination, and faith-based invulnerability to HIV infection. Many believed that one will not die of acquired immune deficiency syndrome if it is not ordained by God. The sex workers also had a high level of HIV-related stigma. CONCLUSION: From these findings, most sex workers considered risk reduction and in particular condom use as far beyond their control or even unnecessary, as a result of their strong beliefs in fatalism and predestination. Therefore, one critical area of intervention is the need to assist sex workers to develop accurate means of assessing their personal vulnerability and self-appraisal of HIV-related risk. PMID- 22096412 TI - Seroprevalence of Toxoplasma gondii IgG antibody in HIV-infected patients at the Lagos University Teaching Hospital. AB - BACKGROUND: Toxoplasmosis is caused by infection with a ubiquitous intracellular protozoan parasite, Toxoplasma gondii. With the advent of the HIV pandemic in Nigeria, toxoplasmic encephalitis has become one of the more frequent opportunistic infections and the most commonly implicated cause of focal brain lesions complicating the course of AIDS. OBJECTIVES: This study was conducted to compare the pattern of seroprevalence of T. gondii (Toxo-IgG) antibodies among HIV-infected persons presenting with neurological complications and those without. MATERIALS AND METHODS: Plasma specimens collected from 380 subjects were tested for Toxo- IgG antibodies by enzyme immunoassay technique and CD4 estimation by flow cytometry. Close-ended questionnaires were applied to all respondents to collect relevant data, with ethical approval from the hospital ethical committee. Plasma was obtained from two study groups comprising 300 HIV positive respondents without neurological presentations, and 80 HIV-positive respondents with neurological complications. RESULTS: Seroprevalence of Toxo-IgG antibodies was 58% in the HIV-positive study group without neurological complications (of these, 79.2% were males and 38.5% were females) and 40% in the study group with neurological complications (46.2% of these were males and 28.6% were females). The overall seroprevalence of Toxo-IgG antibodies among the HIV positive respondents (with and without neurological complications) was 54.2% (206 of 380). Seroprevalence of Toxo-IgG antibodies was lowest among the educated subjects (19% of the respondents with tertiary education) and among females in both study groups. A higher proportion of the subjects with neurological complications had CD4 cell count <100 cells/MUL compared with respondents without neurological defects (39% vs 22.7%; P = 0.000), but the seroprevalence of Toxo IgG antibodies was higher in subjects without neurological complications (45% vs 31.3%; P = 0.000). CONCLUSION: Toxoplasmosis, though an important opportunistic infection in our environment, may not account for the majority of neurological complications observed in patients with HIV infection in our center. PMID- 22096413 TI - Brief Interventions for Tobacco Users: Using the Internet to Train Healthcare Providers. AB - One fifth of Americans smoke; many have no plans to quit. Motivational Interviewing (MI) is an effective approach to intervention with precontemplative smokers, yet a substantial number of healthcare practitioners lack training in this approach. Two interactive online tutorials were developed to teach practitioners to deliver brief tobacco cessation interventions grounded in the MI approach. The tutorials emphasized the unique aspects of working with precontemplative smokers, incorporating audio and video examples of best practices, interactive exercises, targeted feedback, and practice opportunities. One hundred and fifty-two healthcare providers-in-training were randomly assigned to use the online tutorials or to read training material that was matched for content. A virtual standardized patient evaluation was given before and after the training. Both groups improved their scores from pre- to posttest; however, the tutorial group scored significantly better than the reading group at posttest. The results of this study demonstrate the promise of interactive online tutorials as an efficient and effective way to deliver clinical education. PMID- 22096415 TI - Orthodontic considerations for the patient wearing a Milwaukee Brace. PMID- 22096414 TI - The pathomechanical etiology of post-traumatic osteoarthritis following intraarticular fractures. AB - Many intra-articular fracture patients eventually experience significant functional deficits, pain, and stiffness from post-traumatic osteoarthritis (PTOA). Over the last several decades, continued refinement of surgical reconstruction techniques has failed to markedly improve patient outcomes. New treatment paradigms are needed - ideally, bio/pharmaceutical. Progress in that direction has been impeded because the pathomechanical etiology of PTOA development is poorly understood. In particular, the relative roles and pathomechanisms of acute joint injury (from the initial trauma) versus chronic contact stress elevation (from residual incongruity) are unknown, primarily because there have been no objective methods for reliably quantifying either of these insult entities. Over the past decade, novel enabling technologies have been developed that provide objective biomechanical indices of injury severity and of chronic contact stress challenge to fractured joint surfaces. The severity of the initial joint injury is indexed primarily on the basis of the energy released in fracture, obtained from validated digital image analysis of CT scans. Chronic contact stress elevations are indexed by patient-specific finite element stress analysis, using models derived from post-reduction CT scans. These new measures, conceived in the laboratory, have been taken through the stage of validation, and then have been applied in studies of intra-articular fracture patients, to relate these biomechanical indices of cartilage insult to the incidence and severity of PTOA This body of work has provided a novel framework for developing and testing new approaches to forestall PTOA following intra articular fractures. PMID- 22096416 TI - The Ponseti method in Latin America: initial impact and barriers to its diffusion and implementation. AB - The Ponseti method for correcting clubfoot is a safe, effective, and minimally invasive treatment that has recently been implemented in Latin America. This study evaluates the initial impact and unique barriers to the diffusion of the Ponseti method throughout this region. Structured interviews were conducted with 30 physicians practicing the Ponseti method in three socioeconomically diverse countries: Chile, Peru and Guatemala. Since learning the Ponseti method, these physicians have treated approximately 1,740 clubfoot patients, with an estimated 1,705 (98%) patients treated using the Ponseti method, and 35 (2%) patients treated using surgical techniques. The barriers were classified into the following themes: physician education, health care system of the country, culture and beliefs of patients, physical distance and transport, financial barriers for patients, and parental compliance with the method. The results yielded several common barriers throughout Latin America including lack of physician education, physical distance to the treatment centers, and financial barriers for patients. Information from this study can be used to inform, and to implement and evaluate specific strategies to improve the diffusion of the Ponseti method for treating clubfoot throughout Latin America. PMID- 22096417 TI - Diffusion of innovation: enhancing the dissemination of the Ponseti method in Latin America through virtual forums. AB - This ethnographic study evaluated the use of low-bandwidth web-conferencing to enhance diffusion of a specific best practice, the Ponseti method to treat clubfoot, in three economically diverse countries in Latin America. A "Ponseti Virtual Forum" (PVF) was organized in Guatemala, Peru and Chile to examine the influences of economic level and telecommunication infrastructure on the effectiveness of tins approach. Across the three countries, a total of 14 different sites participated in the PVFs. Thirty-three Ponseti-trained practitioners were interviewed before and after each PVF, which included interactions with a Spanish-speaking Ponseti method expert. Semi-structured interviews, observations, and IP address data were triangulated and analyzed. The results demonstrated that 100% of the practitioners rated the sessions as very useful and that they would use this approach again. The largest obstacles to using PVFs were financial (7 out of 9 practitioners) in Guatemala; a lack of equipment and network access (6 out of 11) in Peru; and the organization and implementation of the conferences themselves (7 out of 9) in Chile. This study illustrates the usefulness of Ponseti Virtual Forums in Latin America. Health officials in Peru are currently developing a large-scale information session for traumatologists about the Ponseti method, while practitioners in Guatemala and Chile are organizing monthly scholarly meetings for physicians in remote areas. This initial feedback suggests that low-bandwidth web-conferencing can be an important vehicle for the dissemination of best practices, such as the Ponseti method, in developing countries. PMID- 22096418 TI - Ponseti Brasil: a national program to eradicate neglected clubfoot - preliminary results. AB - BACKGROUND: After hearing about the reproducible and excellent results of the Ponseti method for clubfoot treatment, a group of Brazilian orthopaedic surgeons organized and participated in a standardized national program to teach the Ponseti technique in 21 different cities across Brazil. METHODS: A total of 21 Ponseti symposiums were organized in a standard fashion from January, 2007 to December, 2008. They consisted of a two-day program with lectures, hands-on cast application, and discussion of local clinical cases presented by orthopaedic surgeons. Thirteen Brazilian orthopaedic surgeons, who had been trained by the University of Iowa or centers recognized by them, taught the method. Financial support for travel was provided by an English charity: La Vida (Vital Investment for Developing Aid in Latin America). The physicians who attended the symposiums answered questionnaires before and after the training. RESULTS: About 7% of the 8000 orthopaedic surgeons in Brazil (556 orthopaedic surgeons) were trained. These orthopaedic surgeons stated that they had treated about 4905 babies in the previous year via other methods, including extensive surgery. Seventeen percent of the surgeons did not know about the Ponseti technique at the start of the symposium. Eighty-eight percent reported they felt able to treat children with the Ponseti technique after the symposium. Ninety-four percent of respondents reported that the symposium changed their way of treating clubfoot CONCLUSIONS: These Ponseti symposiums brought about an exchange of medical information and empowered the participants. This program is a good educational tool which can be used in eradicating neglected clubfoot in Brazil. PMID- 22096419 TI - Comparison of hospital costs and duration of treatment with two different clubfoot protocols. PMID- 22096420 TI - Reliability of various observers in determining common radiographic parameters of adult hip structural anatomy. AB - BACKGROUND: Radiographic evaluation of the hip is extremely important in the diagnosis and treatment decisionmaking process for pre-arthritic hip disease. Many different radiographic measurements have been described as indicators of underlying structural hip deformity. The purpose of this study was to determine the interobserver and intraobserver reliability of various musculoskeletal physicians in performing selected measurements of adult structural hip anatomy. METHODS: A blinded review of 45 sets of radiographs from patients with developmental dysplasia, femoro-acetabular impingement, and normal anatomy was performed. Data points included the lateral center-edge angle (LCEA), vertical center-anterior angle (VCA), head-neck offset ratio (UNO), alpha angle, Tonnis angle, Tonnis osteoarthritis grade and a radiographic diagnosis. One orthopaedic fellow, two orthopaedic residents, and two attending musculoskeletal physiatrists analyzed radiographs on two separate occasions. One sports medicine orthopaedic attending physician completed a single analysis of the image sets. Intraobserver and interobserver reliability was established using intra-class correlation coefficients (ICC) for continuous variables. Agreement regarding categorical variables was performed using the kappa coefficient RESULTS: Excellent intraobserver reliability was found for the following: LCEA (ICC = 0.88), VCA (0.88), Tonnis angle (0.83), HNO on the frog lateral (0.78), alpha angle on the frog lateral (0.76), HNO on the cross-table lateral (0.75), and angle alpha on the cross-table lateral (0.76). Intraobserver reliability for osteoarthritis grade was poor (weighted kappa = 0.57). For all data points, interobserver reliability was considerably worse, with 95% confidence intervals spanning below 0.55. CONCLUSIONS: While the described measurements of adult structural hip anatomy provide excellent reliability for a given reader, these measurements are less reliable across readers. Taken in isolation, these measurements, as performed by observers with varied clinical experience and clinical backgrounds, are limited in determining a consistent radiographic diagnosis. PMID- 22096421 TI - Concomitant infection and local metal reaction in patients undergoing revision of metal on metal total hip arthroplasty. AB - Total hip arthroplasty (THA) with conventional polyethylene bearings is traditionally the standard operative treatment for endstage arthritis of the hip. This design has excellent survivorship in most populations, with a low occurrence of infection and other associated complications. Due to concern over increased wear in younger, more active populations, other bearing surfaces have been evaluated, particularly metal-on-metal with wear rates theorized to be lower than conventional THA. Unique to metal-on-metal THA, however, is the possibility of local soft tissue reactions that can mimic infection, making proper diagnosis and treatment difficult. We present a case series of nine hips in eight patients undergoing revision of metal-on-metal THA for local soft tissue reactions, three of which were also found to be concomitantly infected. The laboratory and hip aspirate data described show significant overlap between the infected and non infected cases. Care must be taken when evaluating patients with failed metal-on metal THA as there may be an increased incidence of co-infection in this group of patients. PMID- 22096422 TI - Demographic and comorbid disparities based on payer type in a total joint arthroplasty cohort: implications in a changing health care arena. AB - INTRODUCTION: The purpose of this study was to compare differences in demographic, functional, access to care, and comorbidity data between a Medicaid and Iowa Care (state Medicaid) insured patient cohort and Medicare and a Commercial Payer patient cohort undergoing lower extremity total joint arthroplasty (TJA). MATERIAL & METHODS: A retrospective review of 874 primary TKAs and THAs by a single surgeon at an academic institution between January, 2004 and June, 2008 was performed. Data on the primary insurance payer was used to stratify the cohort into two groups; Medicaid and Iowa Care (state Medicaid) insured and Medicare and commercial payer. Demographic, functional, access to care, and comorbidity data obtained from a standard preoperative survey were compared. RESULTS: Of 874 primary TKAs and THAs, 18.3 % of patients were Medicaid and Iowa Care insured, while 81.7 % were insured by Medicare and commercial payer. Average age was 53.7 and 62.3 respectively, while average BMI was 35.2 and 32.9 respectively. The Medicaid and Iowa Care group was found to be 3 times more likely to smoke tobacco (25.2% v. 8.3%). Preoperative WOMAC Function scores were 33.9 and 46.8, respectively. Self reported diabetes was used as a general surrogate for health comorbidities and occurred in 12.3 % and 11.5%, respectively. Distance traveled was used as a general surrogate for access to care with averages of 92.5 miles and 62.8 miles, respectively. CONCLUSION: The Medicaid and Iowa Care (state Medicaid) group had significantly higher rates of smoking, were significantly younger, and had significantly lower WOMAC scores (p<0.05) preoperatively. BMI comparison showed a trend to greater obesity in the Medicaid and Iowa Care cohort (p=0.056). Diabetes rates were comparable between the two cohorts. Medicaid and Iowa Care patients traveled 29.7 miles farther, suggesting they had less access to local orthopaedic care. There are major differences in comorbidities and patient demographics between payer types. PMID- 22096423 TI - Hinged cast brace for persistent flexion contracture following total knee replacement. AB - The reported incidence of persistent knee flexion contracture following total knee arthroplasty (TKA) has varied from 1-15 percent Various treatment modalities have been described in attempts to manage this often difficult problem. This paper describes a novel method of treatment by using a hinged cast brace (previously reported for treatment of femur fractures and knee contractures secondary to hemophilia and cerebral palsy) for use in patients with symptomatic knee flexion contractures. Application of this cast brace with frequent adjustment (every three to four days, initially) toward full extension can often improve knee extension, after physical therapy and other modalities such as extension-assist braces have failed. Care must be taken in the application and use of this device which utilizes frequent manipulations to reduce and maintain the knee flexion angle. We report two clinical cases in which this protocol was effectively used in decreasing symptomatic knee flexion contractures. PMID- 22096424 TI - Range of motion and patient satisfaction with traditional and high-flexion rotating-platform knees. AB - Although a high degree of flexion is necessary for some activities of daily living, most total knee arthroplasty implants are designed to provide only up to 120 degrees of flexion. Some new designs claim to provide greater flexion. In this retrospective study, we evaluated the Sigma rotating-platform high-flex knee against the traditional Sigma rotating-platform knee (DePuy, Warsaw, IN). There were 153 knees evaluated. We matched the subjects primarily on preoperative flexion and had 64 matched pairs. We also evaluated the knees based on their preoperative flexion, either <120 degrees or >=120 degrees . In comparing the two implants, there were no significant differences in the patients' overall satisfaction, flexion gained or lost, or the need for further surgery. This study was approved by an institutional review board. PMID- 22096425 TI - Efficacy and cost-effectiveness of a blood salvage system in primary total knee arthroplasty--a retrospective match-controlled chart review. AB - We retrospectively reviewed the clinical and cost effectiveness of the OrthoPAT blood salvage system (Haemonetics Corp., Braintree, MA) following total knee arthroplasty (TKA). Two-hundred-and-two patients who received the OrthoPAT system were matched to 202 controls. A second match was performed for subjects weighing <75 kg. For all matched subjects, no significant difference in allogeneic blood transfusion (ABT) rate was found between the control and study groups (p=0.55). In the subjects <75 kg, use of the OrthoPAT system almost halved the incidence of ABT; however, in this small population the result was not statistically significant (p=0.10). Blood management costs for study patients were significantly higher than those of the control group in both the total matched pairs and those <75 kg (p< 0.0001 and p= 0.05, respectively). PMID- 22096426 TI - Assessment of walking pattern pre and post peri-acetabular osteotomy. AB - BACKGROUND: Adult hip dysplasia (AHD) is a common etiology of hip pain in the young adult. Patients with adult hip dysplasia may present with hip pain and early degenerative changes resulting from elevated cumulative hip-contact stress. While there are numerous studies using radiographic parameters coupled with general and disease-specific health status measures to demonstrate that periacetabular osteotomy improves the orientation of the acetabulum, decreases pain and improves function, to our knowledge there is only one study that utilized gait analysis to demonstrate an objective functional alteration. The purpose of the present study was to prospectively evaluate the walking pattern and assess the activity level of patients undergoing periacetabular osteotomy for symptomatic adult hip dysplasia. METHODS: Institutional review board approval was obtained for collection and review of data on 55 patients who underwent periacetabular osteotomy at one institution by the senior author (TM) between the years 2007-2009. Walking pattern characteristics were assessed including velocity, cadence, stride length of the affected side, and percent of single-limb support on the affected limb using GaitRite(r) walking pattern analysis. Activity was assessed as average steps/day over a consecutive seven-day period. As a secondary analysis, the disease-specific and generalized health status outcome measures of all patients who underwent periacetabular osteotomy were reviewed. RESULTS: At an average of 11.5 months post periacetabular osteotomy the walking patterns of 27 patients were available for review. Several trends were observed, including an approximate 5% increase in walking velocity (118 cm/sec to 125 cm/sec), and a 4.5 % increase in stride length (132 cm to 138 cm, p=0.01). At a mean 9.5 months following surgery, 26 patients reported an 8.75% decrease in average steps taken daily (4598 steps/day to 4196 steps/day). A significant improvement in SF-36 PC scores (p<0.01), the WOMAC hip pain and function scores (p<0.01) and the HHS (p<0.01) was noted during the same period. CONCLUSION: At an average of 11.5 months following periacetabular osteotomy for the treatment of symptomatic hip dysplasia, a trend toward increased walking velocity and a significant increase in stride length was noted. A significant improvement in pain relief as well as improved physical function was observed in the short term. Subgroup analysis of patients without pre-existing osteoarthritis (as compared to those with pre-existing osteoarthrosis) revealed increased walking velocity, stride length of the affected limb, and percent of gait cycle in single support on the affected limb following periacetabular osteotomy. Further prospective studies are needed to fully clarify the long-term impact of the periacetabular osteotomy on patients with symptomatic hip dysplasia. PMID- 22096427 TI - Quantifying the effects of extensor mechanism medializatlon procedures using MRI: a cadaver-based study. AB - BACKGROUND: Patellofemoral joint kinematics are dependent on a variety of anatomical features. One of the most common causes of patellar instability is malalignment of the quadriceps extensor mechanism. The Southwick-Fulkerson osteotomy focuses on correcting malalignment of the quadriceps extensor mechanism through medialization of the tibial tubercle. MRI, in conjunction with established patellofemoral indices, allows quantitative evaluation of the patellofemoral joint during active quadriceps extension both pre- and postoperatively. PURPOSE: This study aims to quantitatively evaluate the effects of extensor mechanism medialization procedures using established patellofemoral indices in order to establish a relationship between tubercle transfer distance and patellar tracking. It is believed that a 15mm medial transfer of the tibial tubercle will produce statistically significant changes in patellar tracking when evaluated during active quadriceps contraction. METHODS: Four fresh-frozen cadavers underwent a modified Fulkerson osteotomy. The central quadriceps tendon was identified and traction was applied with a vector parallel to the femoral diaphysis using sutures, to simulate active quadriceps contraction. MRI images were obtained following Omm (control) and 15mm tibial tubercle medialization. Each knee was evaluated at 30, 20, 10, and 0 degrees of flexion. RESULTS: Quantitative evaluation of patellar tracking during active quadriceps contraction detected significant changes in patellar translation following 15mm medial transfer of the tibial tubercle as compared to the control. The significantly reduced indices suggest reduced patellar lateralization and improved patellar tracking during the critical range of motion from 30 to 0 degrees of flexion. CONCLUSIONS: The results of this study indicate that significant quantitative changes in patellar tracking occur following 15mm tibial tubercle medialization when evaluated during active quadriceps contraction using MRI in conjunction with established patellofemoral indices. These findings suggest that quantitative evaluation of patellar tracking may be a valuable pre- and postoperative tool when coupled with qualitative clinical findings. PMID- 22096428 TI - Integrating carthage-specific T1rho MRI into knee clinic diagnostic imaging. AB - With a rise in post-traumatic osteoarthritis, OA no longer is considered just a disease of aging. The 'gold standard' for OA diagnosis has long been planar radiographs for visualizing osteophytes, joint space narrowing and sclerotic changes. A typical magnetic resonance imaging (MRI) protocol will acquire proton density, T1, T2, and fat suppressed images that give a comprehensive picture of morphologic changes associated with injury and subsequent degenerative processes. However, the earliest events of cartilage degeneration occur within the tissue, before measureable changes in morphology. MRI methods have been proposed to display and quantify changes in composition and integrity of such elements of cartilage extracellular matrix as collagen and proteoglycan (PG) content in vivo. T1rho the spin-lattice relaxation time in the rotating frame, has come to the forefront for visualizing water proton-PG interactions in articular cartilage. The purpose of this T1rho MRI study was to define an objective femoral condyle specific registration method, in which zone-dependent cartilage compositional changes could be assessed from the bone outward through the existing cartilage, at pre-ACL reconstruction and subsequent follow-up times, when the loss of thickness to surface-down cartilage erosion might occur later in the OA pathogenesis. Additionally, this study explores the effects of reducing the number of spin-lock times on the absolute T1rho relaxation times; a major parameter in expanding T1rho coverage to the whole joint while satisfying clinical imaging time and specific absorption rate (SAR) safety constraints. The developed image analysis tools serve as the first step toward quantitative functional assessment of cartilage health with noninvasive T1rho MRI, which has the potential to become an important new tool for the early diagnosis of cartilage degeneration following ACL trauma. PMID- 22096429 TI - Digital soft tissue trauma: a concise primer of soft tissue reconstruction of traumatic hand injuries. PMID- 22096430 TI - Arthroscopic subacromial decompression: acromioplasty versus bursectomy alone- does it really matter? A systematic review. AB - BACKGROUND: Subacromial impingement is a common disorder mat in some cases results in surgical management. Arthroscopic subacromial bursectomy alone or in combination with acromioplasty are treatment options when non-operative measures fail. METHODS: A systematic review of all level-I and level-II studies regarding subacromial bursectomy and acromioplasty for impingement was performed. Medline publications were reviewed for appropriate studies. RESULTS: A total of six studies that met inclusion criteria were identified. However, only one randomized study was identified that directly compared the treatments in question. Additionally, only one prospective study of subacromial bursectomy was identified. A comparison of similar outcome measures revealed bursectomy alone provided similar results to bursectomy with acromioplasty. DISCUSSION: Limited high-level studies are available regarding arthroscopic treatment of subacromial impingement. Data available currently suggests that bursectomy alone provides similar outcomes to bursectomy with acromioplasty. PMID- 22096432 TI - The value of physical examination in conjunction with a survey for identifying youth pitchers with arm pain. AB - OBJECTIVE: The purpose of this study is to evaluate the effectiveness of a screening survey in identifying injuries in youth baseball pitchers. It is hypothesized that a standalone survey is unlikely to give a complete picture and that an additional physical examination is necessary to identify all injuries. METHODS: Seventy-seven youth baseball players who pitched in the last 12 months completed the survey. Players underwent physical examination if they reported a history of time-loss injury (16 players) or if they had any current complaints of pain without a history of time-loss injury (22 players). RESULTS: This screening protocol resulted in positive physical examination findings in 37.6% of all 77 players. This included a rate of 56.3% of pitchers with a positive time-loss injury history and 90.9% of pitchers with a negative time-loss injury, but positive complaint of pain. The most common complaint in both groups was elbow tenderness with the most common location being the medial epicondyle. CONCLUSION: While the survey was effective at identifying time-loss injuries, it may neglect more mild injuries, underestimating the percentage of players with pain and positive physical examination findings. The high frequency of positive examination findings in athletes without a history of time-loss injury demands further investigation. PMID- 22096431 TI - Mechanical behavior of carpal tunnel subsynovial connective tissue under compression. AB - Subsynovial connective tissue (SSCT) is a fluid-permeated loose connective tissue that occupies the majority of the space in the carpal tunnel not occupied by the digital flexor tendons or the median nerve. It is arranged in layers around these more discrete structures, presumably to assist with tendon gliding. As a result of this arrangement, the compressive behavior and the fluid permeability of this tissue may substantially affect the stresses in the median nerve resulting from contact with its neighboring tendons or with the walls of the tunnel itself. These stresses may contribute to damage of the median nerve and the development of carpal tunnel syndrome. In this study, the fluid permeability and the compressive behavior of the SSCT were investigated to better understand the mechanics of this tissue and how it may mediate mechanical insult to the median nerve. A custom experimental apparatus was built to allow simultaneous measurement of tissue compression and fluid flow. Using Darcy's law, the average SSCT fluid permeability was 8.78*10(15) m(4)/Ns. The compressive behavior of the SSCT demonstrated time dependence, with an initial modulus of 395kPa gradually decreasing to a value of 285kPa. These baseline tissue data may serve as a mechanical norm (toward which pathological tissue might be returned, therapeutically) and may serve as essential properties to include in future mechanical models of the carpal tunnel. PMID- 22096433 TI - Conical, radiographic, and patient-reported results of surface replacing proximal interphalangeal joint arthroplasty of the hand. AB - The purpose of this study was to evaluate the one-year clinical, radiologic and patient-reported results of surface-replacing proximal interphalangeal joint arthroplasty (SR-PIP) of the hand. Fifteen patients with 18 joints underwent the procedure, and nine patients with 11 joints had follow-up of at least one year's duration. Of these joints, six had a diagnosis of osteoarthritis with no history of trauma, three had post-traumatic arthritis, one had psoriatic arthritis, and one had erosive arthritis. The mean clinical follow-up was at 3.3 years, and the mean radiographic follow-up was at 3.1 years. The average post-operative gain in range of motion at the PIP joint was 28 degrees and was statistically significant. Six patients completed self-reported questionnaires at a mean of 4.8 years post-operatively. The mean Disabilities of the Arm, Shoulder and Hand (DASH) score post-operatively was 17, and the Michigan Hand Questionnaire (MHQ) score for overall satisfaction was 70. There were three complications but only one reoperation. Seven of 11 joints showed some evidence of subsidence on follow up radiographic examination. However, no joints were revised secondary to loosening. Longer follow-up is needed to determine if this observable radiologic subsidence leads to symptomatic loosening of the implant. PMID- 22096434 TI - Extremity sarcoma surgery in younger children: ten years of patients ten years and under. AB - Sarcoma surgeons face unique challenges in younger patients with significant skeletal growth remaining. The heightened concerns regarding radiation in the very young and the drastic changes expected in the lengths and cross-sectional areas of bones affect the decision-making for both soft-tissue and bone sarcomas in this population. Nonetheless, there is sparse literature focused on sarcoma surgery in this age group. The records of one tertiary regional sarcoma treatment program were reviewed to identify all patients ten years old or younger at the time of local control surgery for limb or limb-girdle sarcomas. Demographic information, diagnosis, surgery performed, complications, and general outcomes were gleaned from the medical records. 43 patients were identified, including 15 with osteosarcomas, 11 Ewing's sarcoma family tumors, five rhabdomyosarcomas, and two synovial sarcomas, among others. Location of tumors varied widely, but demonstrated a predilection for the upper extremity more than is typical in adolescents with the same tumor types. Survival was favorable overall, with only five patients dying from disease. Most patients continued to function well at latest follow-up, but 16 experienced additional surgical interventions following the index procedure. Sarcoma surgery in the younger growing child presents challenges for the surgeon, patient, and parents, but is usually successful in the long-term. PMID- 22096435 TI - Chondrosarcoma of the spine: a series of 16 cases and a review of the literature. AB - Only a few major studies of chondrosarcoma of the mobile spine have been reported. These studies have shown that spinal chondrosarcomas require complete surgical resection and are notoriously resistant to chemotherapy and radiation. We present 16 cases of chondrosarcoma of the mobile spine diagnosed at a median age of 54.5 (range 20 - 79) years. Diagnosis and treatment studies were based on both CT scans and MRI. Fifteen of our 16 patients had low-grade (grade 1-2) chondrosarcomas. All patients were treated with surgical resection. Fourteen patients had total resection while two patients had subtotal resection. The two patients who had subtotal resection died of their disease. Five of the fourteen patients who had total resection also died. The mean interval to death was 3.6 years. This study confirms that although chondrosarcomas of the spine are low grade, they are dangerous neoplasms. Even with complete resection, they have a high rate of recurrence and metastasis. PMID- 22096436 TI - Patterns of improvement following oncologic reconstructrion compared to total knee arthroplasty and revision knee arthroplasty. AB - Limb salvage surgery for primary malignant bone tumors of the lower limbs requires complete resection of the tumor, followed by a reconstruction to restore function. In contrast to the abundant information on total knee arthroplasty, data on the recovery pattern of limb salvage surgery is largely limited. With the aim of guiding patient expectations and optimizing care, we retrospectively compared the clinical outcomes among patients following oncologic knee reconstruction, primary total knee arthroplasty, and revision total knee arthroplasty. From January, 2001 to June, 2009, we identified a cohort of 503 primary total knee arthroplasties, 55 revision knee arthroplasties, and 15 oncologic reconstructions. Outcomes were assessed by the validated Short Form-36 (SF-36) health questionnaire. We found that oncologic patients significantly improved their Physical Component Score at one and minimum two-year follow up compared to baseline (p< 0.05) with the majority of improvement (90%) made within the first year following surgery. This is a similar pattern to that observed following primary and revision total knee arthroplasty. PMID- 22096437 TI - A randomized, prospective study comparing intertrochanteric hip fracture fixation with the dynamic hip screw and the dynamic helical hip system in a community practice. AB - OBJECTIVE: To evaluate the clinical performance of the Dynamic Helical Hip System (DHHS) spiral blade relative to the Dynamic Hip Screw (DHS) lag screw. DESIGN: Randomized prospective study. SETTING: One level-2 trauma center and one level-3 trauma center. PATIENTS: Fifty-one consecutive patients were recruited into the trial. Inclusion criteria included patients over 50 years of age with AO/OTA 31A1 or 31A2 fracture. INTERVENTION: Surgeries were performed by one of 15 participating community orthopaedic surgeons. The patients were randomized to either a DHHS or DHS implant. Follow-up occurred at two weeks and six weeks and then at six-week intervals until healing occurred. MAIN OUTCOME MEASURES: Primary outcome variables included sliding of die implant on the final AP radiographs, failure by cut-out and implant failure. RESULTS: There were 24 patients in the DHS group and 27 in the DHHS group. There was no difference in age, gender, ASA score, fracture classification or in the quality of reduction measured on the immediate postoperative radiographs (p=0.28) between the two groups. The tip apex distance was 18.7 mm in the DHHS group and 18.5 mm in the DHS group (p=0.40). The DHHS group had average blade sliding of 7.4 mm while the DHS group had an average lag-screw sliding of 7.7 (p=0.45). The DHHS group had two failures by central protrusion of the blade through the femoral head without significant varus collapse or superior migration. One was revised to a DHS and healed, the other was revised to a proximal femoral locking plate, which also failed and eventually required revision to a total hip arthroplasty. Investigation of the implants post failure showed evidence of binding of the blade shaft in the barrel as a mechanism of failure in both cases. No DHS implants cut out in this series, although one patient was revised to a total hip arthroplasty for symptomatic segmental osteonecrosis. CONCLUSION: Both implants performed well in a majority of cases. The higher incidence of failure in the DHHS group is concerning, despite the low numbers. The mechanism of failure of the DHHS implant left adequate bone stock for attempts at revision fixation. PMID- 22096438 TI - Children hospitalized with lower extremity fractures in the United States in 2006: a population-based approach. AB - OBJECTIVE: The purpose of this study was to examine the demographic and hospitalization characteristics of children hospitalized with lower extremity fractures in the United States in 2006. METHODS: Children aged 0 to 20 years with a diagnosis of lower extremity fracture in the 2006 Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) were included. Lower extremity fractures were defined by International Classification of Diseases, 9th Revision, Clinical Modification codes 820-829 under "Injury and Poisoning (800-999)." Patient demographic and hospitalization-related data were analyzed by chi-square testing and unbalanced analysis of variance. RESULTS: There were more boys than girls with lower extremity fractures and 53% had private insurance as their primary payer. About one half of the children were between the ages of 13 and 20 years, but all ages were represented from age 0 to 20. White children accounted for 56%. Urban hospitalizations accounted for 93% of cases and 66 percent of admissions were to teaching hospitals. All patients had an average length of stay (LOS) 4.04 days, and infant patients had the longest average LOS of 5.46 days. The average number of diagnoses per patient was 3.07, and the average number of procedures per patient was 2.21. The average charge per discharge was $35,236, and the oldest patients had the largest average charge of $41,907. The average number of comorbidities increased with increasing patient age. There was a 55.6% greater mortality risk in non-teaching hospitals than in teaching hospitals and there was at least ten times the mortality risk in rural hospitals than in urban hospitals. CONCLUSIONS: This study provides an understanding of the demographic and hospitalization characteristics of children with lower extremity fractures in the United States in 2006. This information may be useful in implementing measures to help prevent similar injuries in the future. Further research is required to determine causality of the associations found including increased mortality risk for this population at rural and non-teaching hospitals. PMID- 22096439 TI - Gluteal compartment syndrome and superior gluteal artery injury as a result of simple hip dislocation: a case report. AB - Gluteal compartment syndrome as a result of hematoma from a ruptured superior gluteal artery is exceedingly rare; to date, one similar case in a pelvic fracture model has been reported. We report a case of acute gluteal compartment syndrome from a ruptured superior gluteal artery resulting from a simple posterior hip dislocation in an otherwise healthy young male. Timely surgical exploration, evacuation of the hematoma, and achievement of hemostasis allowed for an excellent outcome at follow-up. We review the gluteal compartments as well as treatment protocols for this injury. PMID- 22096440 TI - Treatment of posttraumatic labral interposition with surgical hip dislocation and labral repair. AB - We report a case of a 12-year-old male with delayed presentation of a spontaneous incongruous reduction of a hip dislocation due to labral-chondral acetabular rim fragment entrapment The patient was treated with a staged hip arthroscopy and subsequent surgical dislocation and open repair. At two-year follow-up, the patient had an excellent clinical and radiographic outcome. PMID- 22096441 TI - Open pelvic fractures: the University of Tennessee Medical Center at Knoxville experience over ten years. AB - INTRODUCTION: Open fractures of the pelvis remain a devastating injury with a high mortality and morbidity. Such injuries require an aggressive treatment plan and the coordination of trauma and orthopaedic surgeons to achieve the best outcomes. We report our experience at the University of Tennessee Medical Center at Knoxville with open pelvic fractures over the last ten years. METHODS: After IRB and institutional approval, we reviewed patients admitted with a diagnosis of open fracture of the pelvis from 1999 to 2009. Demographic and admission data were recorded in the trauma registry (TRACS) of the Level I Trauma Center, serving the 1.2 million people living in the regions of east Tennessee, western North Carolina and southeastern Kentucky. Data on fractures were obtained from review of the medical records and radiographs within the chart. RESULTS: There were 3053 pelvic fractures from January 1999 to December 2009. There were 231 deaths in this group (6%) and ages ranged from 18 to 89 years old and Injury Severity Scores ranged from 4 to 75, with a mean of 18.3. Seventy five percent of patients were able to be discharged home. Fifty-two fractures were open. There were 43 men and the mean age was 39 years old. Average ISS was 23 and ranged from 5 to 50. There were 10 deaths (19%) and eight patients underwent angioembolization for control of bleeding (3 deaths). Motorcycle crashes were the most frequent cause of an open fracture, with lateral compression injuries representing 71%. A defined algorithm for fracture management has been in place and employed to assure adequate resuscitation and fracture care and is presented. DISCUSSION: Open pelvic fractures are usually the result of a high energy transfer, and convey a high morbidity and mortality. A defined resuscitation and fixation strategy improves outcome from historical reports. Injuries from penetrating mechanisms are associated with less morbidity and lower mortality. PMID- 22096442 TI - Proximal junctional kyphosis in adult reconstructive spine surgery results from incomplete restoration of the lumbar lordosis relative to the magnitude of the thoracic kyphosis. AB - BACKGROUND: PROXIMAL JUNCTIONAL KYPHOSIS (PJK) IS DEFINED AS: 1) Proximal junction sagittal Cobb angle >>=10 degrees , and 2) Proximal junction sagittal Cobb angle of at least 10 degrees greater than the pre-operative measurement PJK is a common complication which develops in 39% of adults following surgery for spinal deformity. The pathogenesis, risk factors and prevention of this complication are unclear. METHODS: Of 54 consecutive adults treated with spinal deformity surgery (age>=59.3+/-10.1 years), 19 of 54 (35%) developed PJK. The average follow-up was 26.8 months (range 12 - 42). Radiographic parameters were measured at the pre-operative, early postoperative (4-6 weeks), and final follow up visits. Sagittal alignment was measured by the ratio between the C7-plumbline and the sacral-femoral distance. Binary logistic regression model with predictor variables included: Age, BMI, C7-plumbline, and whether lumbar lordosis, thoracic kyphosis and sacral slope were present RESULTS: Patients who developed PJK and those without PJK presented with comparable age, BMI, pelvic incidence and sagittal imbalance before surgery. They also presented with comparable sacral slope and lumbar lordosis. The average magnitude of thoracic kyphosis was significantly larger than the lumbar lordosis in the proximal junctional kyphosis group, both at baseline and in the early postoperative period, as represented by [(-lumbar )lordosis - (thoracic kyphosis)]; no- PJK versus PJK; 6.6 degrees +/ 23.2 degrees versus -6.6 degrees +/-14.2 degrees ; p>=0.012. This was not effectively addressed with surgery in the PJK group [(-LL-TK): 6.2 degrees +/ 13.1 degrees vs. -5.2 degrees +/-9.6 degrees ; p>=0.004]. This group also presented with signs of pelvic retroversion with a sacral slope of 29.3 degrees +/-8.2 degrees pre-operatively that was unchanged after surgery (30.4 degrees +/ 8.5 degrees postoperatively). Logistic regression determined that the magnitude of thoracic kyphosis and sagittal balance (C7-plumbline) was the most important predictor of proximal junctional kyphosis. CONCLUSIONS: Proximal junctional kyphosis developed in those patients where the thoracic kyphosis remained greater in magnitude relative to the lumbar lordosis, and where the sagittal balance seemed corrected, but part of thise correction was secondary to pelvic retroversion. LEVEL OF EVIDENCE: Prognostic case-control study - Level III. PMID- 22096443 TI - Cervical laminoplasty construct stability: an experimental and finite element investigation. AB - STUDY DESIGN: Experimental and finite element investigation of cervical laminoplasty. OBJECTIVE: To determine the stability of the construct post cervical laminoplasty. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty is a widely used technique to widen the spinal canal dimensions without permanently removing the dorsal elements of the cervical spine. Although various laminoplasty procedures have been developed recently, the use of mini-plates to hold the lamina open and prevent restenosis of the spinal cord is a fairly new method and has not been thoroughly investigated. METHODS: Biomechanical compression tests and finite element analyses were performed in this study. Sixteen cervical vertebrae (C3 - C6) were isolated from six cadaveric cervical spines (age at death 68 to 91 years; mean 85 years) and were used for compression tests. Out of the 16 vertebrae, four were without any surgical intervention and the remaining 12 were implanted with one of the two laminoplasty plates: open door (OD) graft. Each vertebra was randomly assigned to one of the three groups: OD plate (6), graft plate (6) or intact vertebrae (4). The intact and implanted vertebrae were potted and loaded to failure. Cross-head displacements and the corresponding reaction force throughout the test were recorded to determine the failure loads. A finite element model of the C5 cervical vertebra was created to accommodate the laminoplasty implants. Experimental loading and boundary conditions were simulated and the stress distribution in the lamina was predicted in response to the compressive loads. RESULTS: A substantial increase in the sagittal canal diameter (27%-33%) and the spinal canal area (31.2%-47%) was observed at all levels. The strength of the implanted specimens was considerably decreased (by six to eight times) as compared to the intact specimens. CONCLUSION: Experimentally obtained data can be combined with mathematical models, such as finite element models, to accurately predict the biomechanical behavior (stresses and strains) of implants and the posterior bone which may not be possible by the use of any other method. PMID- 22096444 TI - Cervical synovial cyst: case report. AB - A 47-year-old female school teacher with a six-week history of left-sided scapular and arm pain is presented. We report her evaluation and treatment Although lumbar degenerative synovial cysts have been reported over 200 times in the literature,6 cervical synovial cysts are much more rare. This case reports a cervicothoracic junction degenerative synovial cyst presenting as radiculopathy. PMID- 22096445 TI - Early spondylodiscitis presenting with single vertebral body involvement: a report of two cases. AB - Infectious spondylodiscitis is an uncommon disease with increasing incidence that typically presents with abnormalities in two adjacent vertebral bodies and the intervening disk. We describe two cases that initially presented with imaging abnormalities in only a single vertebral body. Both patients had a history of lumbar back pain and elevated inflammatory markers, but the lack of classical spondylodiscitis imaging findings led to diagnostic delay and confusion. It is likely that the incidence of atypical presentations of spondylodiscitis will increase as the disease incidence increases and imaging is performed at an earlier stage. It is important to recognize the disease early because early diagnosis is the key to preventing serious complications like epidural abscess and spinal cord compression. PMID- 22096446 TI - Ulnar nerve component to innervation of thumb carpometacarpal joint. AB - PURPOSE: Thumb carpometacarpal (CMC) joint arthritis is one of the most common problems addressed by hand surgeons. The gold standard of treatment for thumb CMC joint arthritis is trapeziectomy, ligament reconstruction and tendon interposition. Denervation of the thumb CMC joint is not currently used to treat arthritis in this joint due to the failure of the procedure to yield significant symptomatic relief. The failure of denervation is puzzling, given that past anatomic studies show the radial nerve is the major innervation of the thumb CMC joint with the lateral antebrachial nerve and the median nerve also innervating this joint. Although no anatomic study has ever shown that the ulnar nerve innervates the CMC joint, due to both the failure of denervation and the success of arthroscopic thermal ablation, we suspect that previous anatomic studies may have overlooked innervation of the thumb CMC joint via the ulnar nerve. METHODS: We dissected 19 formalin-preserved cadaveric hand-to-mid-forearm specimens. The radial, median and ulnar nerves were identified in the proximal forearm and then followed distally. Any branch heading toward the radial side of the hand were followed to see if they innervated the thumb CMC joint. RESULTS: Eleven specimens (58%) had superficial radial nerve innervation to the thumb CMC joint. Nine specimens (47%) had median nerve innervation from the motor branch. Nine specimens (47%) had ulnar nerve innervation from the motor branch. CONCLUSIONS: We believe this is the first study to demonstrate that the ulnar nerve innervates the thumb CMC joint This finding may explain the poor results seen in earlier attempts at denervation of the thumb CMC, but the more favorable results with techniques such as arthroscopy with thermal ablation. PMID- 22096447 TI - The course of the distal saphenous nerve: a cadaveric investigation and clinical implications. AB - INTRODUCTION: Injury to the saphenous nerve at the ankle has been described as a complication resulting from incision and dissection over the distal tibia and medial malleolus. However, the exact course and location of the distal saphenous nerve is not well described in the literature. The purpose of this study was to determine the distal limit of the saphenous nerve and its anatomic relationship to commonly identified orthopaedic landmarks and surgical incisions. METHODS: Sixteen cadaveric ankles were examined at the level of the distal tibia medial malleolus. An incision was made along the medial aspect of the lower extremity from the knee to the hallux to follow the course and branches of the saphenous nerve under direct visualization. We recorded the shortest distance from the most distal visualized portion of the saphenous nerve to the tip of the medial malleolus, to the antero-medial arthroscopic portal site, and to the tibialis anterior tendon. RESULTS: The saphenous nerve runs posterior to the greater saphenous vein in the leg and divides into an anterior and posterior branch approximately 3 cm proximal to the tip of the medial malleolus. These branches terminate in the integument proximal to the tip of the medial malleolus, while the vein continues into the foot. The anterior branch ends at the anterior aspect of the medial malleolus near the posterior edge of the greater saphenous vein. The posterior branch ends near the posterior aspect of the medial malleolus. The average distance from the distal-most visualized aspect of the saphenous nerve to the tip of the medial malleolus measured 8mm +/-; 5mm; from the nerve to the medial arthroscopic portal measured 14mm +/-2mm; and from the nerve to the tibialis anterior measured 16mm +/-3mm. In only one case (of 16) was there an identifiable branch of the saphenous nerve extending to the foot and in this specimen it extended to the first metatarsophalangeal joint. The first metatarsophalangeal joint was innervated by the superficial peroneal nerve in all cases. Small variations were also noted. DISCUSSION AND CONCLUSIONS: This study highlights the proximity of the distal saphenous nerve to common landmarks in orthopaedic surgery. This has important clinical implications in ankle arthroscopy, tarsal tunnel syndrome, fixation of distal tibia medial malleolar fractures, and other procedures centered about the medial malleolus. While the distal course of the saphenous nerve is generally predictable, variations exist and thus the orthopaedic surgeon must operate cautiously to prevent iatrogenic injury. To avoid saphenous nerve injury, incisions should stay distal to the tip of the medial malleolus. The medial arthroscopic portal should be more than one centimeter from the anterior aspect of the medial malleolus which will also avoid the greater saphenous vein. Incision over the anterior tibialis tendon should stay within one centimeter of the medial edge of the tendon. PMID- 22096448 TI - A brief (and somewhat personal) history of the orthopaedic clinic at the University of Iowa Hospitals and Clinics, 1978-2011. PMID- 22096449 TI - Predictive measures of a resident's performance on written Orthopaedic Board scores. AB - OBJECTIVE: Residency programs are continually attempting to predict the performance of both current and potential residents. Previous studies have supported the use of USMLE Steps 1 and 2 as predictors of Orthopaedic In-Training Examination (OITE) and eventual American Board of Orthopaedic Surgery success, while others show no significant correlation. A strong performance on OITE examinations does correlate with strong residency performance, and some believe OITE scores are good predictors of future written board success. The current study was designed to examine potential differences in resident assessment measures and their predictive value for written boards. DESIGN/METHODS: A retrospective review of resident performance data was performed for the past 10 years. Personalized information was removed by the residency coordinator. USMLE Step 1, USMLE Step 2, Orthopaedic In-Training Examination (from first to fifth years of training), and written orthopaedic specialty board scores were collected. Subsequently, the residents were separated into two groups, those scoring above the 35(th) percentile on written boards and those scoring below. Data were analyzed using correlation and regression analyses to compare and contrast the scores across all tests. RESULTS: A significant difference was seen between the groups in regard to USMLE scores for both Step 1 and 2. Also, a significant difference was found between OITE scores for both the second and fifth years. Positive correlations were found for USMLE Step 1, Step 2, OITE 2 and OITE 5 when compared to performance on written boards. One resident initially failed written boards, but passed on the second attempt This resident consistently scored in the 20(th) and 30(th) percentiles on the in-training examinations. CONCLUSIONS: USMLE Step 1 and 2 scores along with OITE scores are helpful in gauging an orthopaedic resident's performance on written boards. Lower USMLE scores along with consistently low OITE scores likely identify residents at risk of failing their written boards. Close monitoring of the annual OITE scores is recommended and may be useful to identify struggling residents. Future work involving multiple institutions is warranted and would ensure applicability of our findings to other orthopedic residency programs. PMID- 22096450 TI - Grammatical form and semantic context in verb learning. AB - Decades of research have documented that young word learners have more difficulty learning verbs than nouns. Nonetheless, recent evidence has uncovered conditions under which children as young as 24 months succeed. Here, we focus in on the kind of linguistic information that undergirds 24-month-olds' success. We introduced 24-month-olds to novel words (either nouns or verbs) as they watched dynamic scenes (e.g., a man waving a balloon); the novel words were presented in semantic contexts that were either rich (e.g., The man is pilking a balloon), or more sparse (e.g., He's pilking it). Toddlers successfully learned nouns in both the semantically rich and sparse contexts, but learned verbs only in the rich context. This documents that to learn the meaning of a novel verb, English acquiring toddlers take advantage of the semantically rich information provided in lexicalized noun phrases. Implications for cross-linguistic theories of acquisition are discussed. PMID- 22096451 TI - Microscopic Symmetry Imposed by Rotational Symmetry Boundary Conditions in Molecular Dynamics Simulation. AB - A large number of viral capsids, as well as other macromolecular assemblies, have icosahedral structure or structures with other rotational symmetries. This symmetry can be exploited during molecular dynamics (MD) to model in effect the full viral capsid using only a subset of primary atoms plus copies of image atoms generated from rotational symmetry boundary conditions (RSBC). A pure rotational symmetry operation results in both primary and image atoms at short range, and within nonbonded interaction distance of each other, so that nonbonded interactions can not be specified by the minimum image convention and explicit treatment of image atoms is required. As such an unavoidable consequence of RSBC is that the enumeration of nonbonded interactions in regions surrounding certain rotational axes must include both a primary atom and its copied image atom, thereby imposing microscopic symmetry for some forces. We examined the possibility of artifacts arising from this imposed microscopic symmetry of RSBC using two simulation systems: a water shell and human rhinovirus 14 (HRV14) capsid with explicit water. The primary unit was a pentamer of the icosahedron, which has the advantage of direct comparison of icosahedrally equivalent spatial regions, for example regions near a 2-fold symmetry axis with imposed symmetry and a 2-fold axis without imposed symmetry. Analysis of structural and dynamic properties of water molecules and protein atoms found similar behavior near symmetry axes with imposed symmetry and where the minimum image convention fails compared with that in other regions in the simulation system, even though an excluded volume effect was detected for water molecules near the axes with imposed symmetry. These results validate the use of RSBC for icosahedral viral capsids or other rotationally symmetric systems. PMID- 22096453 TI - Trade-offs and constraints in allosteric sensing. AB - Sensing extracellular changes initiates signal transduction and is the first stage of cellular decision-making. Yet relatively little is known about why one form of sensing biochemistry has been selected over another. To gain insight into this question, we studied the sensing characteristics of one of the biochemically simplest of sensors: the allosteric transcription factor. Such proteins, common in microbes, directly transduce the detection of a sensed molecule to changes in gene regulation. Using the Monod-Wyman-Changeux model, we determined six sensing characteristics--the dynamic range, the Hill number, the intrinsic noise, the information transfer capacity, the static gain, and the mean response time--as a function of the biochemical parameters of individual sensors and of the number of sensors. We found that specifying one characteristic strongly constrains others. For example, a high dynamic range implies a high Hill number and a high capacity, and vice versa. Perhaps surprisingly, these constraints are so strong that most of the space of characteristics is inaccessible given biophysically plausible ranges of parameter values. Within our approximations, we can calculate the probability distribution of the numbers of input molecules that maximizes information transfer and show that a population of one hundred allosteric transcription factors can in principle distinguish between more than four bands of input concentrations. Our results imply that allosteric sensors are unlikely to have been selected for high performance in one sensing characteristic but for a compromise in the performance of many. PMID- 22096452 TI - Neural dynamics as sampling: a model for stochastic computation in recurrent networks of spiking neurons. AB - The organization of computations in networks of spiking neurons in the brain is still largely unknown, in particular in view of the inherently stochastic features of their firing activity and the experimentally observed trial-to-trial variability of neural systems in the brain. In principle there exists a powerful computational framework for stochastic computations, probabilistic inference by sampling, which can explain a large number of macroscopic experimental data in neuroscience and cognitive science. But it has turned out to be surprisingly difficult to create a link between these abstract models for stochastic computations and more detailed models of the dynamics of networks of spiking neurons. Here we create such a link and show that under some conditions the stochastic firing activity of networks of spiking neurons can be interpreted as probabilistic inference via Markov chain Monte Carlo (MCMC) sampling. Since common methods for MCMC sampling in distributed systems, such as Gibbs sampling, are inconsistent with the dynamics of spiking neurons, we introduce a different approach based on non-reversible Markov chains that is able to reflect inherent temporal processes of spiking neuronal activity through a suitable choice of random variables. We propose a neural network model and show by a rigorous theoretical analysis that its neural activity implements MCMC sampling of a given distribution, both for the case of discrete and continuous time. This provides a step towards closing the gap between abstract functional models of cortical computation and more detailed models of networks of spiking neurons. PMID- 22096454 TI - Hypertension in Cardiovascular and Kidney Disease. AB - The relationship between hypertension and chronic kidney disease (CKD) is bidirectional in nature and, generally, management strategies for cardiovascular risk reduction also attenuate progression of CKD. Prevalent hypertension increases with diminishing kidney function, and the management strategy changes with level of kidney function. In this review, we will examine the evidence for management of hypertension, as a modifiable risk factor for cardiovascular disease in CKD, and the impact of this management on progression of CKD. PMID- 22096455 TI - Possible Mechanisms of Local Tissue Renin-Angiotensin System Activation in the Cardiorenal Metabolic Syndrome and Type 2 Diabetes Mellitus. AB - The role of local tissue renin-angiotensin system (tRAS) activation in the cardiorenal metabolic syndrome (CRS) and type 2 diabetes mellitus (T2DM) is not well understood. To this point, we posit that early redox stress-mediated injury to tissues and organs via accumulation of excessive reactive oxygen species (ROS) and associated wound healing responses might serve as a paradigm to better understand how tRAS is involved. There are at least five common categories responsible for generating ROS that may result in a positive feedback ROS-tRAS axis. These mechanisms include metabolic substrate excess, hormonal excess, hypoxia-ischemia/reperfusion, trauma, and inflammation. Because ROS are toxic to proteins, lipids, and nucleic acids they may be the primary instigator, serving as the injury nidus to initiate the wound healing process. Insulin resistance is central to the development of the CRS and T2DM, and there are now thought to be four major organ systems important in their development. In states of overnutrition and tRAS activation, adipose tissue, skeletal muscle (SkM), islet tissues, and liver (the quadrumvirate) are individually and synergistically related to the development of insulin resistance, CRS, and T2DM. The obesity epidemic is thought to be the driving force behind the CRS and T2DM, which results in the impairment of multiple end-organs, including the cardiovascular system, pancreas, kidney, retina, liver, adipose tissue, SkM, and nervous system. A better understanding of the complex mechanisms leading to local tRAS activation and increases in tissue ROS may lead to new therapies emphasizing global risk reduction of ROS resulting in decreased morbidity and mortality. PMID- 22096457 TI - Prevalence of Subclinical Hypothyroidism in Patients with End-Stage Renal Disease and the Role of Serum Albumin: A Cross-Sectional Study from South India. AB - BACKGROUND/AIM: Subclinical hypothyroidism (SCH) and end-stage renal disease (ESRD) are independent risk factors for cardiovascular mortality. We aimed to study the prevalence of SCH in ESRD patients and assessed its associated risk factors. METHODS: This cross-sectional study was conducted at 2 tertiary-care centers in Chennai, India, over a 3-year period. The study group comprised 137 patients with ESRD on thrice weekly regular maintenance hemodialysis. Free thyroxine (FT(4)) and thyroid-stimulating hormone (TSH) were measured using an electrochemiluminescence immunoassay. SCH was defined as TSH ranging between 4.5 and 10 mIU/l with normal FT(4) (0.93-1.7 ng/dl). Patients with overt hypothyroidism, SCH and overt hyperthyroidism, those on medications affecting thyroid function and pregnant women were excluded from the study. RESULTS: Of 137 ESRD patients (mean age: 43 +/- 13.38 years), 107 were males (78.1%), 45 diabetics (32.8%), 127 hypertensives (92.7%), and 38 smokers (27.7%). Prevalence of SCH was 24.8%. In unadjusted (OR: 3.37, 95% CI: 1.91-5.21) and adjusted (for age, gender, HbA(1C), and albumin/creatinine ratio; OR: 3.11, 95% CI: 2.15-4.98) logistic regression analysis, serum albumin was significantly associated with SCH. Further, multiple linear regression identified that for every 1 g/dl drop in serum albumin TSH increased by 4.61 mIU/l (95% CI: 2.75-5.92). CONCLUSION: We observed a high prevalence of SCH in our ESRD patients. Also, serum albumin was significantly associated with SCH in our study. PMID- 22096456 TI - Prenatal Programming and Epigenetics in the Genesis of the Cardiorenal Syndrome. AB - The presence of a group of interacting maladaptive factors, including hypertension, insulin resistance, metabolic dyslipidemia, obesity, and microalbuminuria and/or reduced renal function, collectively constitutes the cardiorenal metabolic syndrome (CRS). Nutritional and other environmental cues during fetal development can permanently affect the composition, homeostatic systems, and functions of multiple organs and systems; this process has been referred to as 'programming'. Since the original formulation of the notion that low birth weight is a proxy for 'prenatal programming' of adult hypertension and cardiovascular disease, evidence has also emerged for programming of kidney disease, insulin resistance, obesity, metabolic dyslipidemia, and other chronic diseases. The programming concept was initially predicated on the notion that in utero growth restriction due to famine was responsible for increased hypertension, and cardiovascular and renal diseases. On the other hand, we are now more commonly exposed to increasing rates of maternal obesity. The current review will discuss the overarching role of maternal overnutrition, as well as fetal undernutrition, in epigenetic programming in relation to the pathogenesis of the CRS in children and adults. PMID- 22096459 TI - Membrane flow patterns in multicomponent giant vesicles induced by alternating electric fields?Electronic supplementary information (ESI) available: Vesicle preparation procedure, numerical calculations and confocal microscopy movies of domain motion. See DOI: 10.1039/b811876kClick here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file. AB - Alternating electric (AC) fields induce circular patterns of lipid transport in membranes of giant vesicles. The flow is visualized by fluorescently labelled lipid domains. PMID- 22096458 TI - Phosphate Metabolism in Cardiorenal Metabolic Disease. AB - Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the 'normal laboratory range' by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease. PMID- 22096460 TI - Three new Editors! PMID- 22096461 TI - Spontaneous neck haematoma. AB - A 66-year-old Caucasian woman presented with right-sided neck swelling and worsening pain for 5 days. There was no history of trauma, cough or excessive muscular strain. She was not on any anticoagulants or antiplatelet drugs. On initial examination, a 5*4 cm swelling was seen on the trapezius in the posterior triangle of the right side of the neck. The swelling was tender, firm and not mobile on palpation. A CT scan of the neck showed resolving haematoma 3 cm deep to the right trapezius muscle at the level of the hyoid bone. She was treated as an outpatient with analgesics. A repeat CT scan after 4 weeks showed complete resolution of the haematoma. A Medline literature search did not reveal any reported cases of spontaneous haematoma in the posterior triangle of the neck without any precipitating factor. PMID- 22096462 TI - Primary orbital yolk sac tumour in a 14-year-old girl. AB - Yolk sac tumour is a common malignant germ cell tumour, which usually occurs in the testes or ovaries of infants. It can occasionally arise from a number of extragonadal sites. Extragonadal germ cell tumours of the head and neck region account for 5% of all benign and malignant germ cell tumours. The orbit is an extremely unusual location for development of primary yolk sac tumour. The present report concerns the case of a yolk sac tumour in a 14-year-old girl, arising as a primary tumour of the orbit with invasion of periorbital and intracranial spaces. PMID- 22096463 TI - Serous ovarian carcinoma in pregnancy. AB - The diagnosis of ovarian carcinoma in pregnancy is rare (incidence of 0.018 0.073/1000 pregnancies). Its rarity is reflected by a paucity of cases reported in the literature. The present report concerns a case of advanced serous ovarian carcinoma in a full-term pregnancy. This was an incidental finding discovered during an emergency caesarean section for presumed fetal distress. The majority of ovarian carcinomas diagnosed in pregnancy present at early stages, are associated with a good prognosis and are non-epithelial type tumours. Advanced epithelial ovarian carcinoma diagnosed in pregnancy however is associated with a poor prognosis. Case reporting should certainly contain detailed information on clinicopathological variables and treatment regimens. Longer-term maternal and neonatal outcomes are more difficult to substantiate in case reporting. The authors therefore feel that data centralisation would be beneficial in identifying optimal management strategies in these rare tumours and in other malignant tumours diagnosed and treated during pregnancy. PMID- 22096464 TI - Combined penetrating injury of the perineum and abdominal viscera. AB - This is a rare presentation. A farmer aged 52 years old was brought to the emergency service of Government District (Doon) Hospital in the late evening having significant bleeding per rectum. He had injured his perineum on a sharp wooden stick during a fall near a tube well. The wooden stick had been extracted by his relatives, which had resulted in profuse bleeding. The patient was managed with intravenous crystalloids and rushed to the operating theatre for examination under analgesia. Blood transfusion was arranged and the wound explored under general anaesthesia. The patient had unusual associated visceral injuries as well as sphincter, rectum, urinary bladder, ileal loop and mesentery injuries. The injured bowel, mesentery, urinary bladder and rectum were repaired with diversion of the upper pelvic colon. In addition, debridement of the perineal wound with rectal sphincter repair was performed and the presacral space drained. The colostomy was closed after 3 months, and the patient survived and is continent. PMID- 22096465 TI - Cardiac sarcoidosis mimicking arrhythmogenic right ventricular dysplasia. AB - Isolated manifestation of sarcoidosis in the heart is very rare. The present work describes the case of a 41-year-old woman with ventricular tachycardia and severe symptoms of heart failure in June 2006. Clinical, MRI and echocardiographic findings revealed the diagnosis of an arrhythmogenic right ventricular dysplasia. Due to the severe progression of the disease, cardiac transplantation was performed in August 2007. Histopathological examination of the explanted heart, however, revealed numerous non-necrotising granulomas with giant cells, lymphocytic infiltration and interstitial fibrosis, finally confirming the diagnosis of a myocardial sarcoidosis. PMID- 22096466 TI - Intracamaral bevacizumab in neovascular glaucoma with scleromalasia and retinal detachment. PMID- 22096467 TI - Suspension airbags: a potential danger. PMID- 22096468 TI - A fortunate escape from a broken heart: contained ventricular rupture forming a pseudoaneurysm. PMID- 22096469 TI - Acute pancreatitis following paracetamol overdose. AB - A 17-year-old woman presented with acute abdominal pain and vomiting 3 h after she attempted to commit suicide by ingesting 30*500 mg paracetamol tablets. The woman was found to have a raised amylase level, and a CT scan confirmed the diagnosis of acute pancreatitis. According to the Naranjo adverse drug reaction probability scale, it is likely that the pancreatitis was induced by the paracetamol ingestion. A literature search reported 36 cases of pancreatitis following excessive doses of paracetamol, however this possible drug reaction is not widely recognised and not documented in the British National Formulary (BNF) list of possible adverse reactions from paracetamol. Being aware of the possibility that abdominal pain following paracetamol overdose may be a manifestation of pancreatitis can help the early detection and initiation of treatment for pancreatitis. PMID- 22096470 TI - Pacemaker endocarditis: an important clinical entity. AB - Pacemaker endocarditis remains a rare but potentially life threatening complication of pacemaker implantation. This case illustrates a rare cause of pacemaker endocarditis, Serratia marcescens, the management difficulties that can be faced with such organisms, and the potential indolent nature of pacemaker lead associated endocarditis. A review of the current data for pacemaker endocarditis management suggests that treatment with antimicrobials alone is unlikely to be curative and explantation of the device is recommended in all cases of confirmed pacemaker endocarditis (by echocardiography, in correlation with the patient's clinical condition and inflammatory markers). PMID- 22096471 TI - The purple urine bag syndrome. PMID- 22096472 TI - "An unfortunate trip": small bowel perforation in a patient with an undiagnosed inguinal hernia following minor blunt trauma. AB - Small bowel perforation due to blunt abdominal trauma associated with inguinal hernia is uncommon. An 80-year-old woman presented to the emergency department following a simple fall and had developed a traumatic perforation of the proximal ileum likely secondary to an undiagnosed inguinal hernia. Following this minor blunt trauma she recovered after an emergency laparotomy and bowel resection. PMID- 22096473 TI - Spontaneous pneumothorax in the third trimester of pregnancy. AB - The present report concerns a young woman previously diagnosed as having childhood asthma who presented with a secondary spontaneous pneumothorax during the third trimester of pregnancy; at term a caesarean section was recommended for safety reasons. Post partum a severe fixed ventilatory defect unresponsive to inhaled bronchodilator and a short oral course of steroids ruled out asthma. Diffuse bronchiectasis was found on her chest CT scan, although this was not evident clinically. Known aetiologies for diffuse bronchiectasis (cystic fibrosis, anti-alpha1 antitrypsin deficiency, rheumatic diseases, mycobacterial infections, childhood infections and immune deficiencies) were ruled out. Therefore it is believed her bronchiectasis was idiopathic or congenital. No recommendations from recent guidelines on how to manage labour in a woman after a spontaneous pneumothorax could be found. However, a literature search revealed that pregnant women usually experience primary pneumothorax and may continue in natural labour; however, it is unknown how best to manage a woman with secondary spontaneous pneumothorax. PMID- 22096474 TI - In-cell click labelling of small molecules to determine subcellular localisation. AB - Small molecule fluorometric boron dipyrromethene probes were developed to bind hepatitis C virus-encoded NS5A protein and aid subcellular distribution studies. These molecules did not co-locate with NS5A, therefore alternative 'silent' azide reporters were used to obtain a more relevant picture of their distribution. Following pre-incubation with replicon cells, click chemistry was used to append a fluorophore to the azide that confirmed the co-localisation of the small molecule with the NS5A protein, thus providing greater insight into the antiviral mode of action of this chemotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12154-010-0047-1) contains supplementary material, which is available to authorized users. PMID- 22096475 TI - Job Strain, Workplace Discrimination, and Hypertension among Older Workers: The Health and Retirement Study. AB - Job strain has been associated with hypertension among younger workers; however, whether this relationship persists among older workers, particularly older racial/ethnic minorities, is unresolved. This study evaluated whether job strain and workplace discrimination are associated with hypertension and poor blood pressure control among older workers and whether these relationships vary by gender and race/ethnicity. Data were drawn from the Health and Retirement Study, and analysis was restricted to employed participants with complete information on job strain and blood pressure (N = 3,794). In adjusted models, high job strain was associated with lower likelihood of hypertension (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.63, 0.89) relative to low job strain. Stratified analyses indicated this association was only significant among white (OR: 0.71, 95% CI: 0.58, 0.86) and male (OR: 0.61, 95% CI: 0.47, 0.79) workers. High job strain was not significantly associated with hypertension among African American (OR: 1.14, 95% CI: 0.63, 2.07) or Hispanic (OR: 0.56, 95% CI: 0.29, 1.09) workers. Workplace discrimination was not associated with hypertension among any group. Neither job strain nor discrimination was associated with poor blood pressure control. These findings suggest that persistence in work characterized by high job strain in later life may signal resilience to the influence of work related stressors on health. Future research efforts should examine the factors that contribute to gender and racial differences in these relationships. PMID- 22096476 TI - Down-regulation of EBV-LMP1 radio-sensitizes nasal pharyngeal carcinoma cells via NF-kappaB regulated ATM expression. AB - BACKGROUND: The latent membrane protein 1 (LMP1) encoded by EBV is expressed in the majority of EBV-associated human malignancies and has been suggested to be one of the major oncogenic factors in EBV-mediated carcinogenesis. In previous studies we experimentally demonstrated that down-regulation of LMP1 expression by DNAzymes could increase radiosensitivity both in cells and in a xenograft NPC model in mice. RESULTS: In this study we explored the molecular mechanisms underlying the radiosensitization caused by the down-regulation of LMP1 in nasopharyngeal carcinoma. It was confirmed that LMP1 could up-regulate ATM expression in NPCs. Bioinformatic analysis of the ATM ptomoter region revealed three tentative binding sites for NF-kappaB. By using a specific inhibitor of NF kappaB signaling and the dominant negative mutant of IkappaB, it was shown that the ATM expression in CNE1-LMP1 cells could be efficiently suppressed. Inhibition of LMP1 expression by the DNAzyme led to attenuation of the NF-kappaB DNA binding activity. We further showed that the silence of ATM expression by ATM-targeted siRNA could enhance the radiosensitivity in LMP1 positive NPC cells. CONCLUSIONS: Together, our results indicate that ATM expression can be regulated by LMP1 via the NF-kappaB pathways through direct promoter binding, which resulted in the change of radiosensitivity in NPCs. PMID- 22096477 TI - Improved NYVAC-based vaccine vectors. AB - While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-DeltaB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype. PMID- 22096478 TI - Conjunctival reconstruction with progenitor cell-derived autologous epidermal sheets in rhesus monkey. AB - Severe ocular surface diseases are some of the most challenging problems that the clinician faces today. Conventional management is generally unsatisfactory, and the long-term ocular consequences of these conditions are devastating. It is significantly important to find a substitute for conjunctival epithelial cells. This study was to explore the possibility of progenitor cell-derived epidermal sheets on denuded amniotic membrane to reconstruct ocular surface of conjunctiva damaged monkeys. We isolated epidermal progenitor cells of rhesus monkeys by type IV collagen adhesion, and then expanded progenitor cell-derived epidermal sheets on denuded amniotic membrane ex vivo. At 3 weeks after the conjunctiva injury, the damaged ocular surface of four monkeys was surgically reconstructed by transplanting the autologous cultivated epidermal progenitor cells. At 2 weeks after surgery, transplants were removed and examined with Hematoxylin-eosin staining, Periodic acid Schiff staining, immunofluorescent staining, scanning and transmission electron microscopy. Histological examination of transplanted sheets revealed that the cell sheets were healthy alive, adhered well to the denuded amniotic membrane, and had several layers of epithelial cells. Electron microscopy showed that the epithelial cells were very similar in appearance to those of normal conjunctival epithelium, even without goblet cell detected. Epithelial cells of transplants had numerous desmosomal junctions and were attached to the amniotic membrane with hemidesmosomes. Immunohistochemistry confirmed the presence of the conjunctival specific markers, mucin 4 and keratin 4, in the transplanted epidermal progenitor cells. In conclusion, our present study successfully reconstructed conjunctiva with autologous transplantation of progenitor cell-derived epidermal sheets on denuded AM in conjunctival damaged monkeys, which is the first step toward assessing the use of autologous transplantation of progenitor cells of nonocular surface origin. Epidermal progenitor cells could be provided as a new substitute for conjunctival epithelial cells to overcome the problems of autologous conjunctiva shortage. PMID- 22096479 TI - Multiple sites in alphaB-crystallin modulate its interactions with desmin filaments assembled in vitro. AB - The beta3- and beta8-strands and C-terminal residues 155-165 of alphaB-crystallin were identified by pin arrays as interaction sites for various client proteins including the intermediate filament protein desmin. Here we present data using 5 well-characterised alphaB-crystallin protein constructs with substituted beta3- and beta8-strands and with the C-terminal residues 155-165 deleted to demonstrate the importance of these sequences to the interaction of alphaB-crystallin with desmin filaments. We used electron microscopy of negatively stained samples to visualize increased interactions followed by sedimentation assays to quantify our observations. A low-speed sedimentation assay measured the ability of alphaB crystallin to prevent the self-association of desmin filaments. A high-speed sedimentation assay measured alphaB-crystallin cosedimentation with desmin filaments. Swapping the beta8-strand of alphaB-crystallin or deleting residues 155-165 increased the cosedimentation of alphaB-crystallin with desmin filaments, but this coincided with increased filament-filament interactions. In contrast, substitution of the beta3-strand with the equivalent alphaA-crystallin sequences improved the ability of alphaB-crystallin to prevent desmin filament-filament interactions with no significant change in its cosedimentation properties. These data suggest that all three sequences (beta3-strand, beta8-strand and C-terminal residues 155-165) contribute to the interaction of alphaB-crystallin with desmin filaments. The data also suggest that the cosedimentation of alphaB-crystallin with desmin filaments does not necessarily correlate with preventing desmin filament-filament interactions. This important observation is relevant not only to the formation of the protein aggregates that contain both desmin and alphaB crystallin and typify desmin related myopathies, but also to the interaction of alphaB-crystallin with other filamentous protein polymers. PMID- 22096480 TI - Toll-like receptors 2 and 4 regulate the frequency of IFNgamma-producing CD4+ T cells during pulmonary infection with Chlamydia pneumoniae. AB - TLR2 and TLR4 are crucial for recognition of Chlamydia pneumoniae in vivo, since infected TLR2/4 double-deficient mice are unable to control the infection as evidenced by severe loss of body weight and progressive lethal pneumonia. Unexpectedly, these mice display higher pulmonary levels of the protective cytokine IFNgamma than wild type mice. We show here, that antigen-specific CD4(+) T-cells are responsible for the observed IFNgamma-secretion in vivo and their frequency is higher in TLR2/4 double-deficient than in wild type mice. The capacity of TLR2/4 double-deficient dendritic cells to re-stimulate CD4(+) T cells did not differ from wild type dendritic cells. However, the frequency of CD4(+)CD25(+)Foxp3(+) T-cells was considerably higher in wild type compared to TLR2/4 double-deficient mice and was inversely related to the number of IFNgamma secreting CD4(+) effector T-cells. Despite increased IFNgamma-levels, at least one IFNgamma-mediated response, protective NO-secretion, could not be induced in the absence of TLR2 and 4. In summary, CD4(+)CD25(+)Foxp3(+) regulatory T-cells fail to expand in the absence of TLR2 and TLR4 during pulmonary infection with C. pneumoniae, which in turn enhances the frequency of CD4(+)IFNgamma(+) effector T cells. Failure of IFNgamma to induce NO in TLR2/4 double-deficient cells represents one possible mechanism why TLR2/4 double-deficient mice are unable to control pneumonia caused by C. pneumoniae and succumb to the infection. PMID- 22096481 TI - Nogo-receptors NgR1 and NgR2 do not mediate regulation of CD4 T helper responses and CNS repair in experimental autoimmune encephalomyelitis. AB - Myelin-associated inhibition of axonal regrowth after injury is considered one important factor that contributes to regeneration failure in the adult central nervous system (CNS). Blocking strategies targeting this pathway have been successfully applied in several nerve injury models, including experimental autoimmune encephalomyelitis (EAE), suggesting myelin-associated inhibitors (MAIs) and functionally related molecules as targets to enhance regeneration in multiple sclerosis. NgR1 and NgR2 were identified as interaction partners for the myelin proteins Nogo-A, MAG and OMgp and are probably mediating their growth inhibitory effects on axons, although the in vivo relevance of this pathway is currently under debate. Recently, alternative functions of MAIs and NgRs in the regulation of immune cell migration and T cell differentiation have been described. Whether and to what extent NgR1 and NgR2 are contributing to Nogo and MAG-related inhibition of neuroregeneration or immunomodulation during EAE is currently unknown. Here we show that genetic deletion of both receptors does not promote functional recovery during EAE and that NgR1 and NgR2-mediated signals play a minor role in the development of CNS inflammation. Induction of EAE in Ngr1/2-double mutant mice resulted in indifferent disease course and tissue damage when compared to WT controls. Further, the development of encephalitogenic CD4(+) Th1 and Th17 responses was unchanged. However, we observed a slightly increased leukocyte infiltration into the CNS in the absence of NgR1 and NgR2, indicating that NgRs might be involved in the regulation of immune cell migration in the CNS. Our study demonstrates the urgent need for a more detailed knowledge on the multifunctional roles of ligands and receptors involved in CNS regeneration failure. PMID- 22096482 TI - An efficient vector system to modify cells genetically. AB - The transfer of foreign genes into mammalian cells has been essential for understanding the functions of genes and mechanisms of genetic diseases, for the production of coding proteins and for gene therapy applications. Currently, the identification and selection of cells that have received transferred genetic material can be accomplished by methods, including drug selection, reporter enzyme detection and GFP imaging. These methods may confer antibiotic resistance, or be disruptive, or require special equipment. In this study, we labeled genetically modified cells with a cell surface biotinylation tag by co transfecting cells with BirA, a biotin ligase. The modified cells can be quickly isolated for downstream applications using a simple streptavidin bead method. This system can also be used to screen cells expressing two sets of genes from separate vectors. PMID- 22096483 TI - Versican G3 domain modulates breast cancer cell apoptosis: a mechanism for breast cancer cell response to chemotherapy and EGFR therapy. AB - Overexpression of EGFR and versican has been reported in association with breast cancers. Considered oncogenic, these molecules may be attractive therapeutic targets. Possessing anti-apoptotic and drug resistant properties, overexpression of these molecules is accompanied by selective sensitization to the process of apoptosis. In this study, we exogenously expressed a versican G3 construct in breast cancer cell lines and analyzed the effects of G3 on cell viability in fetal bovine serum free conditioned media and evaluated the effects of apoptotic agent C2-ceramide, and chemotherapeutic agents including Docetaxel, Doxorubicin, and Epirubicin. Versican G3 domain enhanced tumor cell resistance to apoptosis when cultured in serum free medium, Doxorubicin, or Epirubicin by up-regulating pERK and GSK-3beta (S9P). However, it could be prevented by selective EGFR inhibitor AG 1478 and selective MEK inhibitor PD 98059. Both AG 1478 and PD 98059 enhanced expression of pSAPK/JNK, while selective JNK inhibitor SP 600125 enhanced expression of GSK-3beta (S9P). Versican G3 promoted cell apoptosis induced by C2-ceramide or Docetaxel by enhancing expression of pSAPK/JNK and decreasing expression of GSK-3beta (S9P), an observation blocked by AG 1478 or SP 6000125. Inhibition of endogenous versican expression by siRNA or reduction of versican G3's expression by linking G3 with 3'UTR prevented G3 modulated cell apoptosis. The dual roles of G3 in modulating breast cancer cell resistance to chemotherapeutic agents may in part explain a potential mechanism for breast cancer cell resistance to chemotherapy and EGFR therapy. The apoptotic effects of chemotherapeutics depend upon the activation and balance of down stream signals in the EGFR pathway. GSK-3beta (S9P) appears to function as a key checkpoint in this balance of apoptosis and anti-apoptosis. Investigation and potential consideration of targeting GSK-3beta (S9P) merits further study. PMID- 22096484 TI - Transcriptome of small regulatory RNAs in the development of the zoonotic parasite Trichinella spiralis. AB - BACKGROUND: Trichinella spiralis is a parasite with unique features. It is a multicellular organism but with an intracellular parasitization and development stage. T. spiralis is the helminthic pathogen that causes zoonotic trichinellosis and afflicts more than 10 million people worldwide, whereas the parasite's biology, especially the developmental regulation is largely unknown. In other organisms, small non-coding RNAs, such as microRNAs (miRNA) and small interfering RNAs (siRNA) execute post-transcriptional regulation by translational repression or mRNA degradation, and a large number of miRNAs have been identified in diverse species. In T. spiralis, the profile of small non-coding RNAs and their function remains poorly understood. METHODOLOGY AND PRINCIPAL FINDINGS: Here, the transcriptional profiles of miRNA and siRNA in three developmental stages of T. spiralis in the rat host were investigated, and compared by high-throughput cDNA sequencing technique ("RNA-seq"). 5,443,641 unique sequence tags were obtained. Of these, 21 represented conserved miRNAs related to 13 previously identified metazoan miRNA families and 213 were novel miRNAs so far unique to T. spiralis. Some of these miRNAs exhibited stage-specific expression. Expression of miRNAs was confirmed in three stages of the life cycle by qRT-PCR and northern blot analysis. In addition, endogenous siRNAs (endo-siRNAs) were found mainly derived from natural antisense transcripts (NAT) and transposable elements (TE) in the parasite. CONCLUSIONS AND SIGNIFICANCE: We provide evidence for the presence of miRNAs and endo-siRNAs in T. spiralis. The miRNAs accounted for the major proportion of the small regulatory RNA population of T. spiralis, while fewer endogenous siRNAs were found. The finding of stage-specific expression patterns of the miRNAs in different developmental stages of T. spiralis suggests that miRNAs may play important roles in parasite development. Our data provide a basis for further understanding of the molecular regulation and functional evolution of miRNAs in parasitic nematodes. PMID- 22096485 TI - Enhanced activity of meprin-alpha, a pro-migratory and pro-angiogenic protease, in colorectal cancer. AB - Meprin-alpha is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-alpha levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-alpha mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-alpha in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)-induced migratory response of meprin-transfected epithelial cells was increased compared to wild-type cells in the presence of plasminogen, and that the angiogenic response in organ-cultured rat aortic explants was enhanced in the presence of exogenous human meprin-alpha. In patients, meprin alpha mRNA was expressed in colonic adenomas, primary tumors UICC (International Union Against Cancer) stage I, II, III and IV, as well as in liver metastases. In contrast, the corresponding protein accumulated only in primary tumors and liver metastases, but not in adenomas. However, liver metastases lacked meprin-alpha activity despite increased expression of the corresponding protein, which correlated with inefficient zymogen activation. Sera from cancer patients exhibited reduced meprin-alpha inhibition compared to healthy controls. In conclusion, meprin-alpha activity is regulated differently in primary tumors and metastases, leading to high proteolytic activity in primary tumors and low activity in liver metastases. By virtue of its pro-migratory and pro-angiogenic activity, meprin-alpha may promote tumor progression in colorectal cancer. PMID- 22096486 TI - The automatic conservative: ideology-based attentional asymmetries in the processing of valenced information. AB - Research has widely explored the differences between conservatives and liberals, and it has been also recently demonstrated that conservatives display different reactions toward valenced stimuli. However, previous studies have not yet fully illuminated the cognitive underpinnings of these differences. In the current work, we argued that political ideology is related to selective attention processes, so that negative stimuli are more likely to automatically grab the attention of conservatives as compared to liberals. In Experiment 1, we demonstrated that negative (vs. positive) information impaired the performance of conservatives, more than liberals, in an Emotional Stroop Task. This finding was confirmed in Experiment 2 and in Experiment 3 employing a Dot-Probe Task, demonstrating that threatening stimuli were more likely to attract the attention of conservatives. Overall, results support the conclusion that people embracing conservative views of the world display an automatic selective attention for negative stimuli. PMID- 22096487 TI - A vicious cycle: a cross-sectional study of canine tail-chasing and human responses to it, using a free video-sharing website. AB - Tail-chasing is widely celebrated as normal canine behaviour in cultural references. However, all previous scientific studies of tail-chasing or 'spinning' have comprised small clinical populations of dogs with neurological, compulsive or other pathological conditions; most were ultimately euthanased. Thus, there is great disparity between scientific and public information on tail chasing. I gathered data on the first large (n = 400), non-clinical tail-chasing population, made possible through a vast, free, online video repository, YouTubeTM. The demographics of this online population are described and discussed. Approximately one third of tail-chasing dogs showed clinical signs, including habitual (daily or 'all the time') or perseverative (difficult to distract) performance of the behaviour. These signs were observed across diverse breeds. Clinical signs appeared virtually unrecognised by the video owners and commenting viewers; laughter was recorded in 55% of videos, encouragement in 43%, and the commonest viewer descriptors were that the behaviour was 'funny' (46%) or 'cute' (42%). Habitual tail-chasers had 6.5+/-2.3 times the odds of being described as 'Stupid' than other dogs, and perseverative dogs were 6.8+/-2.1 times more frequently described as 'Funny' than distractible ones were. Compared with breed- and age-matched control videos, tail-chasing videos were significantly more often indoors and with a computer/television screen switched on. These findings highlight that tail-chasing is sometimes pathological, but can remain untreated, or even be encouraged, because of an assumption that it is 'normal' dog behaviour. The enormous viewing figures that YouTubeTM attracts (mean+/-s.e. = 863+/-197 viewings per tail-chasing video) suggest that this perception will be further reinforced, without effective intervention. PMID- 22096488 TI - The age-related risk of co-existing meningitis in children with urinary tract infection. AB - OBJECTIVE: The primary aim of this study was to determine age-stratified rates of co-existing bacterial meningitis in children with urinary tract infection (UTI). The secondary aims of this study were to determine the causative pathogens of UTI, and the clinical features and outcome of children with co-existing meningitis. METHODS: Analysis of data collected over a nine-year period at a tertiary pediatric hospital in Australia. STUDY POPULATION: children below 16 years of age with culture-confirmed UTI and a paired CSF sample. RESULTS: A total of 748 episodes in 735 cases were included in the final analysis. The commonest pathogens causing UTI were Escherichia coli (67.4%), Enterococcus faecalis (8.4%), Klebsiella oxytoca (3.5%) and Klebsiella pneumoniae (3.5%). Only two (1.2%; 95% CI: 0.15-4.36%) of 163 neonates (between 0 and 28 days of age) with UTI had co-existing meningitis. Both presented with pyrexia, irritability and lethargy, and recovered uneventfully with antibiotic treatment. There were no cases of co-existing meningitis among 499 infants (between 29 days and 12 months of age) with UTI (95% CI: 0.00-0.74%), or any of the 86 children aged 12 months or over (95% CI: 0.00-4.20%). CONCLUSIONS: These findings indicate that clinicians should have a low threshold to perform a lumbar puncture in neonates with UTI, as the risk of co-existing meningitis is not insignificant in this age group. In contrast, beyond the neonatal period, the risk is small and a more selective approach is warranted. PMID- 22096489 TI - Comparative effects of fructose and glucose on lipogenic gene expression and intermediary metabolism in HepG2 liver cells. AB - Consumption of large amounts of fructose or sucrose increases lipogenesis and circulating triglycerides in humans. Although the underlying molecular mechanisms responsible for this effect are not completely understood, it is possible that as reported for rodents, high fructose exposure increases expression of the lipogenic enzymes fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC-1) in human liver. Since activation of the hexosamine biosynthesis pathway (HBP) is associated with increases in the expression of FAS and ACC-1, it raises the possibility that HBP-related metabolites would contribute to any increase in hepatic expression of these enzymes following fructose exposure. Thus, we compared lipogenic gene expression in human-derived HepG2 cells after incubation in culture medium containing glucose alone or glucose plus 5 mM fructose, using the HBP precursor 10 mM glucosamine (GlcN) as a positive control. Cellular metabolite profiling was conducted to analyze differences between glucose and fructose metabolism. Despite evidence for the active uptake and metabolism of fructose by HepG2 cells, expression of FAS or ACC-1 did not increase in these cells compared with those incubated with glucose alone. Levels of UDP-N acetylglucosamine (UDP-GlcNAc), the end-product of the HBP, did not differ significantly between the glucose and fructose conditions. Exposure to 10 mM GlcN for 10 minutes to 24 hours resulted in 8-fold elevated levels of intracellular UDP-GlcNAc (P<0.001), as well as a 74-126% increase in FAS (P<0.05) and 49-95% increase in ACC-1 (P<0.01) expression above controls. It is concluded that in HepG2 liver cells cultured under standard conditions, sustained exposure to fructose does not result in an activation of the HBP or increased lipogenic gene expression. Should this scenario manifest in human liver in vivo, it would suggest that high fructose consumption promotes triglyceride synthesis primarily through its action to provide lipid precursor carbon and not by activating lipogenic gene expression. PMID- 22096490 TI - NASA-approved rotary bioreactor enhances proliferation of human epidermal stem cells and supports formation of 3D epidermis-like structure. AB - The skin is susceptible to different injuries and diseases. One major obstacle in skin tissue engineering is how to develop functional three-dimensional (3D) substitute for damaged skin. Previous studies have proved a 3D dynamic simulated microgravity (SMG) culture system as a "stimulatory" environment for the proliferation and differentiation of stem cells. Here, we employed the NASA approved rotary bioreactor to investigate the proliferation and differentiation of human epidermal stem cells (hEpSCs). hEpSCs were isolated from children foreskins and enriched by collecting epidermal stem cell colonies. Cytodex-3 micro-carriers and hEpSCs were co-cultured in the rotary bioreactor and 6-well dish for 15 days. The result showed that hEpSCs cultured in rotary bioreactor exhibited enhanced proliferation and viability surpassing those cultured in static conditions. Additionally, immunostaining analysis confirmed higher percentage of ki67 positive cells in rotary bioreactor compared with the static culture. In contrast, comparing with static culture, cells in the rotary bioreactor displayed a low expression of involucrin at day 10. Histological analysis revealed that cells cultured in rotary bioreactor aggregated on the micro-carriers and formed multilayer 3D epidermis structures. In conclusion, our research suggests that NASA-approved rotary bioreactor can support the proliferation of hEpSCs and provide a strategy to form multilayer epidermis structure. PMID- 22096491 TI - Facial attractiveness ratings from video-clips and static images tell the same story. AB - Most of what we know about what makes a face attractive and why we have the preferences we do is based on attractiveness ratings of static images of faces, usually photographs. However, several reports that such ratings fail to correlate significantly with ratings made to dynamic video clips, which provide richer samples of appearance, challenge the validity of this literature. Here, we tested the validity of attractiveness ratings made to static images, using a substantial sample of male faces. We found that these ratings agreed very strongly with ratings made to videos of these men, despite the presence of much more information in the videos (multiple views, neutral and smiling expressions and speech-related movements). Not surprisingly, given this high agreement, the components of video-attractiveness were also very similar to those reported previously for static-attractiveness. Specifically, averageness, symmetry and masculinity were all significant components of attractiveness rated from videos. Finally, regression analyses yielded very similar effects of attractiveness on success in obtaining sexual partners, whether attractiveness was rated from videos or static images. These results validate the widespread use of attractiveness ratings made to static images in evolutionary and social psychological research. We speculate that this validity may stem from our tendency to make rapid and robust judgements of attractiveness. PMID- 22096492 TI - Maternal synchronization of gestational length and lung maturation. AB - Among all mammals, fetal growth and organ maturation must be precisely synchronized with gestational length to optimize survival at birth. Lack of pulmonary maturation is the major cause of infant mortality in preterm birth. Whether fetal or maternal genotypes influence the close relationship between the length of gestation and lung function at birth is unknown. Structural and biochemical indicators of pulmonary maturity were measured in two mouse strains whose gestational length differed by one day. Shorter gestation in C57BL/6J mice was associated with advanced morphological and biochemical pulmonary development and better perinatal survival when compared to A/J pups born prematurely. After ovarian transplantation, A/J pups were born early in C57BL/6J dams and survived after birth, consistent with maternal control gestational length. Expression of genes critical for perinatal lung function was assessed in A/J pups born after ovarian transfer. A subset of mRNAs important for perinatal respiratory adaptation was selectively induced in the A/J pups born after ovarian transfer. mRNAs precociously induced after ovarian transfer indicated an important role for the transcription factors C/EBPalpha and CREB in maternally induced lung maturation. We conclude that fetal lung maturation is determined by both fetal and maternal genotypes. Ovarian transfer experiments demonstrated that maternal genotype determines the timing of birth and can influence fetal lung growth and maturation to ensure perinatal survival. PMID- 22096493 TI - Nuclease modulates biofilm formation in community-associated methicillin resistant Staphylococcus aureus. AB - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging contributor to biofilm-related infections. We recently reported that strains lacking sigma factor B (sigB) in the USA300 lineage of CA-MRSA are unable to develop a biofilm. Interestingly, when spent media from a USA300 sigB mutant was incubated with other S. aureus strains, biofilm formation was inhibited. Following fractionation and mass spectrometry analysis, the major anti-biofilm factor identified in the spent media was secreted thermonuclease (Nuc). Considering reports that extracellular DNA (eDNA) is an important component of the biofilm matrix, we investigated the regulation and role of Nuc in USA300. The expression of the nuc gene was increased in a sigB mutant, repressed by glucose supplementation, and was unaffected by the agr quorum-sensing system. A FRET assay for Nuc activity was developed and confirmed the regulatory results. A USA300 nuc mutant was constructed and displayed an enhanced biofilm-forming capacity, and the nuc mutant also accumulated more high molecular weight eDNA than the WT and regulatory mutant strains. Inactivation of nuc in the USA300 sigB mutant background partially repaired the sigB biofilm-negative phenotype, suggesting that nuc expression contributes to the inability of the mutant to form biofilm. To test the generality of the nuc mutant biofilm phenotypes, the mutation was introduced into other S. aureus genetic backgrounds and similar increases in biofilm formation were observed. Finally, using multiple S. aureus strains and regulatory mutants, an inverse correlation between Nuc activity and biofilm formation was demonstrated. Altogether, our findings confirm the important role for eDNA in the S. aureus biofilm matrix and indicates Nuc is a regulator of biofilm formation. PMID- 22096494 TI - A novel, functional and replicable risk gene region for alcohol dependence identified by genome-wide association study. AB - Several genome-wide association studies (GWASs) reported tens of risk genes for alcohol dependence, but most of them have not been replicated or confirmed by functional studies. The present study used a GWAS to search for novel, functional and replicable risk gene regions for alcohol dependence. Associations of all top ranked SNPs identified in a discovery sample of 681 African-American (AA) cases with alcohol dependence and 508 AA controls were retested in a primary replication sample of 1,409 European-American (EA) cases and 1,518 EA controls. The replicable associations were then subjected to secondary replication in a sample of 6,438 Australian family subjects. A functional expression quantitative trait locus (eQTL) analysis of these replicable risk SNPs was followed-up in order to explore their cis-acting regulatory effects on gene expression. We found that within a 90 Mb region around PHF3-PTP4A1 locus in AAs, a linkage disequilibrium (LD) block in PHF3-PTP4A1 formed the only peak associated with alcohol dependence at p<10(-4). Within this block, 30 SNPs associated with alcohol dependence in AAs (1.6*10(-5)<=p<=0.050) were replicated in EAs (1.3*10( 3)<=p<=0.038), and 18 of them were also replicated in Australians (1.8*10( 3)<=p<=0.048). Most of these risk SNPs had strong cis-acting regulatory effects on PHF3-PTP4A1 mRNA expression across three HapMap samples. The distributions of log(p) values for association and functional signals throughout this LD block were highly consistent across AAs, EAs, Australians and three HapMap samples. We conclude that the PHF3-PTP4A1 region appears to harbor a causal locus for alcohol dependence, and proteins encoded by PHF3 and/or PTP4A1 might play a functional role in the disorder. PMID- 22096495 TI - Competing conservation objectives for predators and prey: estimating killer whale prey requirements for Chinook salmon. AB - Ecosystem-based management (EBM) of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca) and their primary prey, Chinook salmon (Oncorhynchus tshawytscha). Both species have at-risk conservation status and transboundary (Canada-US) ranges. We modeled individual killer whale prey requirements from feeding and growth records of captive killer whales and morphometric data from historic live-capture fishery and whaling records worldwide. The models, combined with caloric value of salmon, and demographic and diet data for wild killer whales, allow us to predict salmon quantities needed to maintain and recover this killer whale population, which numbered 87 individuals in 2009. Our analyses provide new information on cost of lactation and new parameter estimates for other killer whale populations globally. Prey requirements of southern resident killer whales are difficult to reconcile with fisheries and conservation objectives for Chinook salmon, because the number of fish required is large relative to annual returns and fishery catches. For instance, a U.S. recovery goal (2.3% annual population growth of killer whales over 28 years) implies a 75% increase in energetic requirements. Reducing salmon fisheries may serve as a temporary mitigation measure to allow time for management actions to improve salmon productivity to take effect. As ecosystem-based fishery management becomes more prevalent, trade-offs between conservation objectives for predators and prey will become increasingly necessary. Our approach offers scenarios to compare relative influence of various sources of uncertainty on the resulting consumption estimates to prioritise future research efforts, and a general approach for assessing the extent of conflict between conservation objectives for threatened or protected wildlife where the interaction between affected species can be quantified. PMID- 22096496 TI - Effect of transmission reduction by insecticide-treated bednets (ITNs) on antimalarial drug resistance in western Kenya. AB - Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1 86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance. PMID- 22096497 TI - Modulation of metabolism and switching to biofilm prevail over exopolysaccharide production in the response of Rhizobium alamii to cadmium. AB - Heavy metals such as cadmium (Cd(2+)) affect microbial metabolic processes. Consequently, bacteria adapt by adjusting their cellular machinery. We have investigated the dose-dependent growth effects of Cd(2+) on Rhizobium alamii, an exopolysaccharide (EPS)-producing bacterium that forms a biofilm on plant roots. Adsorption isotherms show that the EPS of R. alamii binds cadmium in competition with calcium. A metabonomics approach based on ion cyclotron resonance Fourier transform mass spectrometry has showed that cadmium alters mainly the bacterial metabolism in pathways implying sugars, purine, phosphate, calcium signalling and cell respiration. We determined the influence of EPS on the bacterium response to cadmium, using a mutant of R. alamii impaired in EPS production (MSDeltaGT). Cadmium dose-dependent effects on the bacterial growth were not significantly different between the R. alamii wild type (wt) and MSDeltaGT strains. Although cadmium did not modify the quantity of EPS isolated from R. alamii, it triggered the formation of biofilm vs planktonic cells, both by R. alamii wt and by MSDeltaGT. Thus, it appears that cadmium toxicity could be managed by switching to a biofilm way of life, rather than producing EPS. We conclude that modulations of the bacterial metabolism and switching to biofilms prevails in the adaptation of R. alamii to cadmium. These results are original with regard to the conventional role attributed to EPS in a biofilm matrix, and the bacterial response to cadmium. PMID- 22096498 TI - A thermostable beta-glucuronidase obtained by directed evolution as a reporter gene in transgenic plants. AB - A beta-glucuronidase variant, GUS-TR3337, that was obtained by directed evolution exhibited higher thermostability than the wild-type enzyme, GUS-WT. In this study, the utility of GUS-TR337 as an improved reporter was evaluated. The corresponding gus-tr3337 and gus-wt genes were independently cloned in a plant expression vector and introduced into Arabidopsis thaliana. With 4-MUG as a substrate, plants containing the gus-wt gene showed no detectable beta glucuronidase activity after exposure to 60 degrees C for 10 min, while those hosting the gus-tr3337 gene retained 70% or 50% activity after exposure to 80 degrees C for 10 min or 30 min, respectively. Similarly, in vivo beta glucuronidase activity could be demonstrated by using X-GLUC as a substrate in transgenic Arabidopsis plants hosting the gus-tr3337 gene that were exposed to 80 degrees C for up to 30 min. Thus, the thermostability of GUS-TR3337 can be exploited to distinguish between endogenous and transgenic beta-glucuronidase activity, which is a welcome improvement in its use as a reporter. PMID- 22096499 TI - Honey bee dopamine and octopamine receptors linked to intracellular calcium signaling have a close phylogenetic and pharmacological relationship. AB - BACKGROUND: Three dopamine receptor genes have been identified that are highly conserved among arthropod species. One of these genes, referred to in honey bees as Amdop2, shows a close phylogenetic relationship to the a-adrenergic-like octopamine receptor family. In this study we examined in parallel the functional and pharmacological properties of AmDOP2 and the honey bee octopamine receptor, AmOA1. For comparison, pharmacological properties of the honey bee dopamine receptors AmDOP1 and AmDOP3, and the tyramine receptor AmTYR1, were also examined. METHODOLOGY/PRINCIPAL FINDINGS: Using HEK293 cells heterologously expressing honey bee biogenic amine receptors, we found that activation of AmDOP2 receptors, like AmOA1 receptors, initiates a rapid increase in intracellular calcium levels. We found no evidence of calcium signaling via AmDOP1, AmDOP3 or AmTYR1 receptors. AmDOP2- and AmOA1-mediated increases in intracellular calcium were inhibited by 10 uM edelfosine indicating a requirement for phospholipase C beta activity in this signaling pathway. Edelfosine treatment had no effect on AmDOP2- or AmOA1-mediated increases in intracellular cAMP. The synthetic compounds mianserin and epinastine, like cis-(Z)-flupentixol and spiperone, were found to have significant antagonist activity on AmDOP2 receptors. All 4 compounds were effective antagonists also on AmOA1 receptors. Analysis of putative ligand binding sites offers a possible explanation for why epinastine acts as an antagonist at AmDOP2 receptors, but fails to block responses mediated via AmDOP1. CONCLUSIONS/SIGNIFICANCE: Our results indicate that AmDOP2, like AmOA1, is coupled not only to cAMP, but also to calcium-signalling and moreover, that the two signalling pathways are independent upstream of phospholipase C-beta activity. The striking similarity between the pharmacological properties of these 2 receptors suggests an underlying conservation of structural properties related to receptor function. Taken together, these results strongly support phylogenetic analyses indicating that the AmDOP2 and AmOA1 receptor genes are immediate paralogs. PMID- 22096500 TI - Optimization of fermentation conditions and rheological properties of exopolysaccharide produced by deep-sea bacterium Zunongwangia profunda SM-A87. AB - Zunongwangia profunda SM-A87 isolated from deep-sea sediment can secrete large quantity of exopolysaccharide (EPS). Response surface methodology was applied to optimize the culture conditions for EPS production. Single-factor experiment showed that lactose was the best carbon source. Based on the Plackett-Burman design, lactose, peptone and temperature were selected as significant variables, which were further optimized by the steepest ascent (descent) method and central composite design. The optimal culture conditions for EPS production and broth viscosity were determined as 32.21 g/L lactose, 8.87 g/L peptone and an incubation temperature of 9.8 degrees C. Under these conditions, the maximum EPS yield and broth viscosity were 8.90 g/L and 6551 mPa*s, respectively, which is the first report of such high yield of EPS from a marine bacterium. The aqueous solution of the EPS displayed high viscosity, interesting shearing thinning property and great tolerance to high temperature, a wide range of pH, and high salinity. PMID- 22096501 TI - Plant DNA barcodes can accurately estimate species richness in poorly known floras. AB - BACKGROUND: Widespread uptake of DNA barcoding technology for vascular plants has been slow due to the relatively poor resolution of species discrimination (~70%) and low sequencing and amplification success of one of the two official barcoding loci, matK. Studies to date have mostly focused on finding a solution to these intrinsic limitations of the markers, rather than posing questions that can maximize the utility of DNA barcodes for plants with the current technology. METHODOLOGY/PRINCIPAL FINDINGS: Here we test the ability of plant DNA barcodes using the two official barcoding loci, rbcLa and matK, plus an alternative barcoding locus, trnH-psbA, to estimate the species diversity of trees in a tropical rainforest plot. Species discrimination accuracy was similar to findings from previous studies but species richness estimation accuracy proved higher, up to 89%. All combinations which included the trnH-psbA locus performed better at both species discrimination and richness estimation than matK, which showed little enhanced species discriminatory power when concatenated with rbcLa. The utility of the trnH-psbA locus is limited however, by the occurrence of intraspecific variation observed in some angiosperm families to occur as an inversion that obscures the monophyly of species. CONCLUSIONS/SIGNIFICANCE: We demonstrate for the first time, using a case study, the potential of plant DNA barcodes for the rapid estimation of species richness in taxonomically poorly known areas or cryptic populations revealing a powerful new tool for rapid biodiversity assessment. The combination of the rbcLa and trnH-psbA loci performed better for this purpose than any two-locus combination that included matK. We show that although DNA barcodes fail to discriminate all species of plants, new perspectives and methods on biodiversity value and quantification may overshadow some of these shortcomings by applying barcode data in new ways. PMID- 22096502 TI - KIAA0101 is overexpressed, and promotes growth and invasion in adrenal cancer. AB - BACKGROUND: KIAA0101 is a proliferating cell nuclear antigen-associated factor that is overexpressed in some human malignancies. Adrenocortical neoplasm is one of the most common human neoplasms for which the molecular causes are poorly understood. Moreover, it is difficult to distinguish between localized benign and malignant adrenocortical tumors. For these reasons, we studied the expression, function and possible mechanism of dysregulation of KIAA0101 in human adrenocortical neoplasm. METHODOLOGY/PRINCIPAL FINDINGS: KIAA0101 mRNA and protein expression levels were determined in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 adrenocortical carcinoma (ACC). SiRNA knockdown was used to determine the functional role of KIAA0101 on cell proliferation, cell cycle, apoptosis, soft agar anchorage independent growth and invasion in the ACC cell line, NCI-H295R. In addition, we explored the mechanism of KIAA0101 dysregulation by examining the mutational status. KIAA0101 mRNA (9.7 fold) and protein expression were significantly higher in ACC (p<0.0001). KIAA0101 had sparse protein expression in only a few normal adrenal cortex samples, which was confined to adrenocortical progenitor cells. KIAA0101 expression levels were 84% accurate for distinguishing between ACC and normal and benign adrenocortical tumor samples. Knockdown of KIAA0101 gene expression significantly decreased anchorage independent growth by 80% and invasion by 60% (p = 0.001; p = 0.006). We found no mutations in KIAA0101 in ACC. CONCLUSIONS/SIGNIFICANCE: KIAA0101 is overexpressed in ACC. Our data supports that KIAA0101 is a marker of cellular proliferation, promotes growth and invasion, and is a good diagnostic marker for distinguishing benign from malignant adrenocortical neoplasm. PMID- 22096503 TI - Role of SPI-1 secreted effectors in acute bovine response to Salmonella enterica Serovar Typhimurium: a systems biology analysis approach. AB - Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a DeltasipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-beta, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF beta signaling pathways and the regulation of actin cytoskeleton pathway. PMID- 22096504 TI - A genome-wide survey on basic helix-loop-helix transcription factors in giant panda. AB - The giant panda (Ailuropoda melanoleuca) is a critically endangered mammalian species. Studies on functions of regulatory proteins involved in developmental processes would facilitate understanding of specific behavior in giant panda. The basic helix-loop-helix (bHLH) proteins play essential roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in over 20 organisms, including fruit fly, zebrafish, mouse and human. Our present study identified 107 bHLH family members being encoded in giant panda genome. Phylogenetic analyses revealed that they belong to 44 bHLH families with 46, 25, 15, 4, 11 and 3 members in group A, B, C, D, E and F, respectively, while the remaining 3 members were assigned into "orphan". Compared to mouse, the giant panda does not encode seven bHLH proteins namely Beta3a, Mesp2, Sclerax, S-Myc, Hes5 (or Hes6), EBF4 and Orphan 1. These results provide useful background information for future studies on structure and function of bHLH proteins in the regulation of giant panda development. PMID- 22096505 TI - A novel Rho-like protein TbRHP is involved in spindle formation and mitosis in trypanosomes. AB - BACKGROUND: In animals and fungi Rho subfamily small GTPases are involved in signal transduction, cytoskeletal function and cellular proliferation. These organisms typically possess multiple Rho paralogues and numerous downstream effectors, consistent with the highly complex contributions of Rho proteins to cellular physiology. By contrast, trypanosomatids have a much simpler Rho signaling system, and the Trypanosoma brucei genome contains only a single divergent Rho-related gene, TbRHP (Tb927.10.6240). Further, only a single RhoGAP like protein (Tb09.160.4180) is annotated, contrasting with the >70 Rho GAP proteins from Homo sapiens. We wished to establish the function(s) of TbRHP and if Tb09.160.4180 is a potential GAP for this protein. METHODS/FINDINGS: TbRHP represents an evolutionarily restricted member of the Rho GTPase clade and is likely trypanosomatid restricted. TbRHP is expressed in both mammalian and insect dwelling stages of T. brucei and presents with a diffuse cytoplasmic location and is excluded from the nucleus. RNAi ablation of TbRHP results in major cell cycle defects and accumulation of multi-nucleated cells, coinciding with a loss of detectable mitotic spindles. Using yeast two hybrid analysis we find that TbRHP interacts with both Tb11.01.3180 (TbRACK), a homolog of Rho-kinase, and the sole trypanosome RhoGAP protein Tb09.160.4180, which is related to human OCRL. CONCLUSIONS: Despite minimization of the Rho pathway, TbRHP retains an important role in spindle formation, and hence mitosis, in trypanosomes. TbRHP is a partner for TbRACK and an OCRL-related trypanosome Rho-GAP. PMID- 22096506 TI - Cooperation between referees and authors increases peer review accuracy. AB - Peer review is fundamentally a cooperative process between scientists in a community who agree to review each other's work in an unbiased fashion. Peer review is the foundation for decisions concerning publication in journals, awarding of grants, and academic promotion. Here we perform a laboratory study of open and closed peer review based on an online game. We show that when reviewer behavior was made public under open review, reviewers were rewarded for refereeing and formed significantly more cooperative interactions (13% increase in cooperation, P = 0.018). We also show that referees and authors who participated in cooperative interactions had an 11% higher reviewing accuracy rate (P = 0.016). Our results suggest that increasing cooperation in the peer review process can lead to a decreased risk of reviewing errors. PMID- 22096507 TI - Plasmodium falciparum parasites are killed by a transition state analogue of purine nucleoside phosphorylase in a primate animal model. AB - Plasmodium falciparum causes most of the one million annual deaths from malaria. Drug resistance is widespread and novel agents against new targets are needed to support combination-therapy approaches promoted by the World Health Organization. Plasmodium species are purine auxotrophs. Blocking purine nucleoside phosphorylase (PNP) kills cultured parasites by purine starvation. DADMe Immucillin-G (BCX4945) is a transition state analogue of human and Plasmodium PNPs, binding with picomolar affinity. Here, we test BCX4945 in Aotus primates, an animal model for Plasmodium falciparum infections. Oral administration of BCX4945 for seven days results in parasite clearance and recrudescence in otherwise lethal infections of P. falciparum in Aotus monkeys. The molecular action of BCX4945 is demonstrated in crystal structures of human and P. falciparum PNPs. Metabolite analysis demonstrates that PNP blockade inhibits purine salvage and polyamine synthesis in the parasites. The efficacy, oral availability, chemical stability, unique mechanism of action and low toxicity of BCX4945 demonstrate potential for combination therapies with this novel antimalarial agent. PMID- 22096508 TI - Variation in effects of non-Hodgkin lymphoma risk factors according to the human leukocyte antigen (HLA)-DRB1*01:01 allele and ancestral haplotype 8.1. AB - Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03 TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk. PMID- 22096509 TI - Immune response and mitochondrial metabolism are commonly deregulated in DMD and aging skeletal muscle. AB - Duchenne Muscular Dystrophy (DMD) is a complex process involving multiple pathways downstream of the primary genetic insult leading to fatal muscle degeneration. Aging muscle is a multifactorial neuromuscular process characterized by impaired muscle regeneration leading to progressive atrophy. We hypothesized that these chronic atrophying situations may share specific myogenic adaptative responses at transcriptional level according to tissue remodeling. Muscle biopsies from four young DMD and four AGED subjects were referred to a group of seven muscle biopsies from young subjects without any neuromuscular disorder and explored through a dedicated expression microarray. We identified 528 differentially expressed genes (out of 2,745 analyzed), of which 328 could be validated by an exhaustive meta-analysis of public microarray datasets referring to DMD and Aging in skeletal muscle. Among the 328 validated co-expressed genes, 50% had the same expression profile in both groups and corresponded to immune/fibrosis responses and mitochondrial metabolism. Generalizing these observed meta-signatures with large compendia of public datasets reinforced our results as they could be also identified in other pathological processes and in diverse physiological conditions. Focusing on the common gene signatures in these two atrophying conditions, we observed enrichment in motifs for candidate transcription factors that may coordinate either the immune/fibrosis responses (ETS1, IRF1, NF1) or the mitochondrial metabolism (ESRRA). Deregulation in their expression could be responsible, at least in part, for the same transcriptome changes initiating the chronic muscle atrophy. This study suggests that distinct pathophysiological processes may share common gene responses and pathways related to specific transcription factors. PMID- 22096511 TI - A new basal sauropodomorph (Dinosauria: Saurischia) from Quebrada del Barro Formation (Marayes-El Carrizal Basin), northwestern Argentina. AB - BACKGROUND: Argentinean basal sauropodomorphs are known by several specimens from different basins; Ischigualasto, El Tranquilo, and Mogna. The Argentinean record is diverse and includes some of the most primitive known sauropodomorphs such as Panphagia and Chromogisaurus, as well as more derived forms, including several massospondylids. Until now, the Massospondylidae were the group of basal sauropodomorphs most widely spread around Pangea with a record in almost all continents, mostly from the southern hemisphere, including the only record from Antarctica. METHODOLOGY/PRINCIPAL FINDING: We describe here a new basal sauropodomorph, Leyesaurus marayensis gen. et sp. nov., from the Quebrada del Barro Formation, an Upper Triassic-Lower Jurassic unit that crops out in northwestern Argentina. The new taxon is represented by a partial articulated skeleton that includes the skull, vertebral column, scapular and pelvic girdles, and hindlimb. Leyesaurus is diagnosed by a set of unique features, such as a sharply acute angle (50 degrees) formed by the ascending process of the maxilla and the alveolar margin, a straight ascending process of the maxilla with a longitudinal ridge on its lateral surface, noticeably bulging labial side of the maxillary teeth, greatly elongated cervical vertebrae, and proximal articular surface of metatarsal III that is shelf-like and medially deflected. Phylogenetic analysis recovers Leyesaurus as a basal sauropodomorph, sister taxon of Adeopapposaurus within the Massospondylidae. Moreover, the results suggest that massospondylids achieved a higher diversity than previously thought. CONCLUSIONS/SIGNIFICANCE: Our phylogenetic results differ with respect to previous analyses by rejecting the massospondylid affinities of some taxa from the northern hemisphere (e.g., Seitaad, Sarahsaurus). As a result, the new taxon Leyesaurus, coupled with other recent discoveries, suggests that the diversity of massospondylids in the southern hemisphere was higher than in other regions of Pangea. Finally, the close affinities of Leyesaurus with the Lower Jurassic Massospondylus suggest a younger age for the Quebrada del Barro Formation than previously postulated. PMID- 22096510 TI - Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population. AB - BACKGROUND: To investigate whether the candidate genes that confer susceptibility to type 2 diabetes mellitus are also correlated with gestational diabetes mellitus (GDM) in pregnant Chinese women. METHODOLOGY/PRINCIPAL FINDINGS: In this study, 1764 unrelated pregnant women were recruited, of which 725 women had GDM and 1039 served as controls. Six single nucleotide polymorphisms (rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK) were genotyped using TaqMan allelic discrimination assays. The genotype and allele distributions of each SNP between the GDM cases and controls and the combined effects of alleles for the risk of developing GDM were analyzed. We found that the rs4402960, rs2383208 and rs391300 were statistically associated with GDM (OR = 1.207, 95%CI = 1.029-1.417, p = 0.021; OR = 1.242, 95%CI = 1.077-1.432, p = 0.003; OR = 1.202, 95%CI = 1.020-1.416, P = 0.028, respectively). In addition, the effect was greater under a recessive model in rs391300 (OR = 1.820, 95%CI = 1.226-2.701, p = 0.003). Meanwhile, the joint effect of these three loci indicated an additive effect of multiple alleles on the risk of developing GDM with an OR of 1.196 per allele (p = 1.08*10(-4)). We also found that the risk alleles of rs2383208 (b = -0.085, p = 0.003), rs4402960 (b = -0.057, p = 0.046) and rs10830963 (b = -0.096, p = 0.001) were associated with HOMA-B, while rs7754840 was associated with decrease in insulin AUC during a 100 g OGTT given at the time of GDM diagnosis (b = -0.080, p = 0.007). CONCLUSIONS/SIGNIFICANCE: Several risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women. The effects of these SNPs on GDM might be through the impairment of beta cell function and these risk loci contributed additively to the disease. PMID- 22096512 TI - Identification of residues in the heme domain of soluble guanylyl cyclase that are important for basal and stimulated catalytic activity. AB - Nitric oxide signals through activation of soluble guanylyl cyclase (sGC), a heme containing heterodimer. NO binds to the heme domain located in the N-terminal part of the beta subunit of sGC resulting in increased production of cGMP in the catalytic domain located at the C-terminal part of sGC. Little is known about the mechanism by which the NO signaling is propagated from the receptor domain (heme domain) to the effector domain (catalytic domain), in particular events subsequent to the breakage of the bond between the heme iron and Histidine 105 (H105) of the beta subunit. Our modeling of the heme-binding domain as well as previous homologous heme domain structures in different states point to two regions that could be critical for propagation of the NO activation signal. Structure-based mutational analysis of these regions revealed that residues T110 and R116 in the alphaF helix-beta1 strand, and residues I41 and R40 in the alphaB alphaC loop mediate propagation of activation between the heme domain and the catalytic domain. Biochemical analysis of these heme mutants allows refinement of the map of the residues that are critical for heme stability and propagation of the NO/YC-1 activation signal in sGC. PMID- 22096513 TI - Physical fitness and telomere length in patients with coronary heart disease: findings from the Heart and Soul Study. AB - BACKGROUND: Short telomere length (TL) is an independent predictor of mortality in patients with coronary heart disease (CHD). However, the relationship between physical fitness and TL has not been explored in these patients. METHODS: In a cross sectional study of 944 outpatients with stable CHD, we performed exercise treadmill testing, assessed self-reported physical activity, and measured leukocyte TL using a quantitative PCR assay. We used generalized linear models to calculate mean TL (T/S ratio), and logistic regression models to compare the proportion of patients with short TL (defined as the lowest quartile), among participants with low, medium and high physical fitness, based on metabolic equivalent tasks achieved (METs). RESULTS: 229 participants had low physical fitness (<5 METS), 334 had moderate physical fitness (5-7 METS), and 381 had high physical fitness (>7 METS). Mean +/- T/S ratio ranged from 0.86+/-0.21 (5349+/ 3781 base pairs) in those with low physical fitness to 0.95+/-0.23 (5566+/-3829 base pairs) in those with high physical fitness (p<.001). This association remained strong after adjustment for numerous patient characteristics, including measures of cardiac disease severity and physical inactivity (p = 0.005). Compared with participants with high physical fitness, those with low physical fitness had 2-fold greater odds of having TL in the lowest quartile (OR 2.39, 95% CI 1.60-3.55; p<.001). This association was similar after multivariable adjustment (OR 1.94, 95%CI, 1.18-3.20; p = 0.009). Self-reported physical inactivity was associated with shorter TL in unadjusted analyses, but not after multivariable adjustment. CONCLUSIONS: We found that worse objectively-assessed physical fitness is associated with shorter leukocyte telomere length in patients with CHD. The clinical implications of this association deserve further study. PMID- 22096514 TI - Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. AB - Endothelin-1 (ET-1) is a potent vasoconstrictor involved in the regulation of vascular tone and implicated in hypertension. However, the role of small blood vessels endothelial ET-1 in hypertension remains unclear. The present study investigated the effect of chronic over-expression of endothelial ET-1 on arterial blood pressure and vascular reactivity using transgenic mice approach. Transgenic mice (TET-1) with endothelial ET-1 over-expression showed increased in ET-1 level in the endothelial cells of small pulmonary blood vessels. Although TET-1 mice appeared normal, they developed mild hypertension which was normalized by the ET(A) receptor (BQ123) but not by ET(B) receptor (BQ788) antagonist. Tail cuff measurements showed a significant elevation of systolic and mean blood pressure in conscious TET-1 mice. The mice also exhibited left ventricular hypertrophy and left axis deviation in electrocardiogram, suggesting an increased peripheral resistance. The ionic concentrations in the urine and serum were normal in 8-week old TET-1 mice, indicating that the systemic hypertension was independent of renal function, although, higher serum urea levels suggested the occurrence of kidney dysfunction. The vascular reactivity of the aorta and the mesenteric artery was altered in the TET-1 mice indicating that chronic endothelial ET-1 up-regulation leads to vascular tone imbalance in both conduit and resistance arteries. These findings provide evidence for the role of spatial expression of ET-1 in the endothelium contributing to mild hypertension was mediated by ET(A) receptors. The results also suggest that chronic endothelial ET 1 over-expression affects both cardiac and vascular functions, which, at least in part, causes blood pressure elevation. PMID- 22096515 TI - Conflict between genetic and phenotypic differentiation: the evolutionary history of a 'lost and rediscovered' shorebird. AB - Understanding and resolving conflicts between phenotypic and genetic differentiation is central to evolutionary research. While phenotypically monomorphic species may exhibit deep genetic divergences, some morphologically distinct taxa lack notable genetic differentiation. Here we conduct a molecular investigation of an enigmatic shorebird with a convoluted taxonomic history, the White-faced Plover (Charadrius alexandrinus dealbatus), widely regarded as a subspecies of the Kentish Plover (C. alexandrinus). Described as distinct in 1863, its name was consistently misapplied in subsequent decades until taxonomic clarification ensued in 2008. Using a recently proposed test of species delimitation, we reconfirm the phenotypic distinctness of dealbatus. We then compare three mitochondrial and seven nuclear DNA markers among 278 samples of dealbatus and alexandrinus from across their breeding range and four other closely related plovers. We fail to find any population genetic differentiation between dealbatus and alexandrinus, whereas the other species are deeply diverged at the study loci. Kentish Plovers join a small but growing list of species for which low levels of genetic differentiation are accompanied by the presence of strong phenotypic divergence, suggesting that diagnostic phenotypic characters may be encoded by few genes that are difficult to detect. Alternatively, gene expression differences may be crucial in producing different phenotypes whereas neutral differentiation may be lagging behind. PMID- 22096516 TI - Differential immediate and sustained memory enhancing effects of alpha7 nicotinic receptor agonists and allosteric modulators in rats. AB - The alpha7 nicotinic acetylcholine receptor (nAChR) is a potential target for the treatment of cognitive deficits in patients with schizophrenia, ADHD and Alzheimer's disease. Here we test the hypothesis that upregulation of alpha7 nAChR levels underlies the enhanced and sustained procognitive effect of repeated administration of alpha7 nAChR agonists. We further compare the effect of agonists to that of alpha7 nAChR positive allosteric modulators (PAMs), which do not induce upregulation of the alpha7 nAChR. Using the social discrimination test as a measure of short-term memory, we show that the alpha7 nAChR agonist A-582941 improves short-term memory immediately after repeated (7* daily), but not a single administration. The alpha7 nAChR PAMs PNU-120596 and AVL-3288 do not affect short-term memory immediately after a single or repeated administration. This demonstrates a fundamental difference in the behavioral effects of agonists and PAMs that may be relevant for clinical development. Importantly, A-582941 and AVL-3288 increase short-term memory 24 hrs after repeated, but not a single, administration, suggesting that repeated administration of both agonists and PAMs may produce sustained effects on cognitive performance. Subsequent [(125)I] bungarotoxin autoradiography revealed no direct correlation between alpha7 nAChR levels in frontal cortical or hippocampal brain regions and short-term memory with either compound. Additionally, repeated treatment with A-582941 did not affect mRNA expression of RIC-3 or the lynx-like gene products lynx1, lynx2, PSCA, or Ly6H, which are known to affect nAChR function. In conclusion, both alpha7 nAChR agonists and PAMs exhibit sustained pro-cognitive effects after repeated administration, and altered levels of the alpha7 nAChR per se, or that of endogenous regulators of nAChR function, are likely not the major cause of this effect. PMID- 22096517 TI - Noise pollution filters bird communities based on vocal frequency. AB - BACKGROUND: Human-generated noise pollution now permeates natural habitats worldwide, presenting evolutionarily novel acoustic conditions unprecedented to most landscapes. These acoustics not only harm humans, but threaten wildlife, and especially birds, via changes to species densities, foraging behavior, reproductive success, and predator-prey interactions. Explanations for negative effects of noise on birds include disruption of acoustic communication through energetic masking, potentially forcing species that rely upon acoustic communication to abandon otherwise suitable areas. However, this hypothesis has not been adequately tested because confounding stimuli often co-vary with noise and are difficult to separate from noise exposure. METHODOLOGY/PRINCIPAL FINDINGS: Using a natural experiment that controls for confounding stimuli, we evaluate whether species vocal features or urban-tolerance classifications explain their responses to noise measured through habitat use. Two data sets representing nesting and abundance responses reveal that noise filters bird communities nonrandomly. Signal duration and urban tolerance failed to explain species-specific responses, but birds with low-frequency signals that are more susceptible to masking from noise avoided noisy areas and birds with higher frequency vocalizations remained. Signal frequency was also negatively correlated with body mass, suggesting that larger birds may be more sensitive to noise due to the link between body size and vocal frequency. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that acoustic masking by noise may be a strong selective force shaping the ecology of birds worldwide. Larger birds with lower frequency signals may be excluded from noisy areas, whereas smaller species persist via transmission of higher frequency signals. We discuss our findings as they relate to interspecific relationships among body size, vocal amplitude and frequency and suggest that they are immediately relevant to the global problem of increases in noise by providing critical insight as to which species traits influence tolerance of these novel acoustics. PMID- 22096518 TI - Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1. AB - Late-stage neuropathological hallmarks of Alzheimer's disease (AD) are beta amyloid (betaA) and hyperphosphorylated tau peptides, aggregated into plaques and tangles, respectively. Corresponding phenotypes have been mimicked in existing transgenic mice, however, the translational value of aggressive over-expression has recently been questioned. As controlled gene expression may offer animal models with better predictive validity, we set out to design a transgenic mouse model that circumvents complications arising from pronuclear injection and massive over-expression, by targeted insertion of human mutated amyloid and tau transgenes, under the forebrain- and neurone-specific CaMKIIalpha promoter, termed PLB1(Double). Crossing with an existing presenilin 1 line resulted in PLB1(Triple) mice. PLB1(Triple) mice presented with stable gene expression and age-related pathology of intra-neuronal amyloid and hyperphosphorylated tau in hippocampus and cortex from 6 months onwards. At this early stage, pre-clinical (18)FDG PET/CT imaging revealed cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain. Quantitative EEG analyses yielded heightened delta power during wakefulness and REM sleep, and time in wakefulness was already reliably enhanced at 6 months of age. These anomalies were paralleled by impairments in long-term and short-term hippocampal plasticity and preceded cognitive deficits in recognition memory, spatial learning, and sleep fragmentation all emerging at ~12 months. These data suggest that prodromal AD phenotypes can be successfully modelled in transgenic mice devoid of fibrillary plaque or tangle development. PLB1(Triple) mice progress from a mild (MCI-like) state to a more comprehensive AD-relevant phenotype, which are accessible using translational tools such as wireless EEG and microPET/CT. PMID- 22096519 TI - Evidence for thalamic involvement in the thermal grill illusion: an FMRI study. AB - BACKGROUND: Perceptual illusions play an important role in untangling neural mechanisms underlying conscious phenomena. The thermal grill illusion (TGI) has been suggested as a promising model for exploring percepts involved in neuropathic pain, such as cold-allodynia (pain arising from contact with innocuous cold). The TGI is an unpleasant/painful sensation from touching juxtapositioned bars of cold and warm innocuous temperatures. AIM: To develop an MRI-compatible TGI-unit and explore the supraspinal correlates of the illusion, using fMRI, in a group of healthy volunteers. METHODS: We constructed a TGI thermode allowing the rapid presentation of warm(41 degrees C), cold(18 degrees C) and interleaved(41 degrees C+18 degrees C = TGI) temperatures in an fMRI environment. Twenty volunteers were tested. The affective-motivational ("unpleasantness") and sensory-disciminatory ("pain-intensity") dimensions of each respective stimulus were rated. Functional images were analyzed at a corrected alpha-level <0.05. RESULTS: The TGI was rated as significantly more unpleasant and painful than stimulation with each of its constituent temperatures. Also, the TGI was rated as significantly more unpleasant than painful. Thermal stimulation versus neutral baseline revealed bilateral activations of the anterior insulae and fronto-parietal regions. Unlike its constituent temperatures the TGI displayed a strong activation of the right (contralateral) thalamus. Exploratory contrasts at a slightly more liberal threshold-level also revealed a TGI-activation of the right mid/anterior insula, correlating with ratings of unpleasantness (rho = 0.31). CONCLUSION/SIGNIFICANCE: To the best of our knowledge, this is the first fMRI-study of the TGI. The activation of the anterior insula is consistent with this region's putative role in processing of homeostatically relevant feeling-states. Our results constitute the first neurophysiologic evidence of thalamic involvement in the TGI. Similar thalamic activity has previously been observed during evoked cold-allodynia in patients with central neuropathic pain. Our results further the understanding of the supraspinal correlates of the TGI-phenomenon and pave the way for future inquiries into if and how it may relate to neuropathic pain. PMID- 22096520 TI - Percutaneous cryoablation of pulmonary metastases from colorectal cancer. AB - OBJECTIVE: To evaluate the safety and efficacy of cryoablation for metastatic lung tumors from colorectal cancer. METHODS: The procedures were performed on 24 patients (36-82 years of age, with a median age of 62; 17 male patients, 7 female patients) for 55 metastatic tumors in the lung, during 30 sessions. The procedural safety, local progression free interval, and overall survival were assessed by follow-up computed tomographic scanning performed every 3-4 months. RESULTS: The major complications were pneumothorax, 19 sessions (63%), pleural effusion, 21 sessions (70%), transient and self-limiting hemoptysis, 13 sessions (43%) and tract seeding, 1 session (3%). The 1- and 3-year local progression free intervals were 90.8% and 59%, respectively. The 3-years local progression free intervals of tumors <=15 mm in diameter was 79.8% and that of tumors >15 mm was 28.6% (p = 0.001; log-rank test). The 1- and 3-year overall survival rates were 91% and 59.6%, respectively. CONCLUSION: The results indicated that percutaneous cryoablation is a feasible treatment option. The local progression free interval was satisfactory at least for tumors that were <=15 mm in diameter. PMID- 22096521 TI - Anti-transforming growth factor beta antibody treatment rescues bone loss and prevents breast cancer metastasis to bone. AB - Breast cancer often metastasizes to bone causing osteolytic bone resorption which releases active TGFbeta. Because TGFbeta favors progression of breast cancer metastasis to bone, we hypothesized that treatment using anti-TGFbeta antibody may reduce tumor burden and rescue tumor-associated bone loss in metastatic breast cancer. In this study we have tested the efficacy of an anti-TGFbeta antibody 1D11 preventing breast cancer bone metastasis. We have used two preclinical breast cancer bone metastasis models, in which either human breast cancer cells or murine mammary tumor cells were injected in host mice via left cardiac ventricle. Using several in vivo, in vitro and ex vivo assays, we have demonstrated that anti-TGFbeta antibody treatment have significantly reduced tumor burden in the bone along with a statistically significant threefold reduction in osteolytic lesion number and tenfold reduction in osteolytic lesion area. A decrease in osteoclast numbers (p = 0.027) in vivo and osteoclastogenesis ex vivo were also observed. Most importantly, in tumor-bearing mice, anti-TGFbeta treatment resulted in a twofold increase in bone volume (p<0.01). In addition, treatment with anti-TGFbeta antibody increased the mineral-to-collagen ratio in vivo, a reflection of improved tissue level properties. Moreover, anti-TGFbeta antibody directly increased mineralized matrix formation in calverial osteoblast (p = 0.005), suggesting a direct beneficial role of anti-TGFbeta antibody treatment on osteoblasts. Data presented here demonstrate that anti-TGFbeta treatment may offer a novel therapeutic option for tumor-induced bone disease and has the dual potential for simultaneously decreasing tumor burden and rescue bone loss in breast cancer to bone metastases. This approach of intervention has the potential to reduce skeletal related events (SREs) in breast cancer survivors. PMID- 22096522 TI - Cognitive control and individual differences in economic ultimatum decision making. AB - Much publicity has been given to the fact that people's economic decisions often deviate from the rational predictions of standard economic models. In the classic ultimatum game, for example, most people turn down financial gains by rejecting unequal monetary splits. The present study points to neglected individual differences in this debate. After participants played the ultimatum game we tested for individual differences in cognitive control capacity of the most and least economic responders. The key finding was that people who were higher in cognitive control, as measured by behavioral (Go/No-Go performance) and neural (No-Go N2 amplitude) markers, did tend to behave more in line with the standard models and showed increased acceptance of unequal splits. Hence, the cognitively highest scoring decision-makers were more likely to maximize their monetary payoffs and adhere to the standard economic predictions. Findings question popular claims with respect to the rejection of standard economic models and the irrationality of human economic decision-making. PMID- 22096523 TI - Cost-effectiveness of Internet-based self-management compared with usual care in asthma. AB - BACKGROUND: Effectiveness of Internet-based self-management in patients with asthma has been shown, but its cost-effectiveness is unknown. We conducted a cost effectiveness analysis of Internet-based asthma self-management compared with usual care. METHODOLOGY AND PRINCIPAL FINDINGS: Cost-effectiveness analysis alongside a randomized controlled trial, with 12 months follow-up. Patients were aged 18 to 50 year and had physician diagnosed asthma. The Internet-based self management program involved weekly on-line monitoring of asthma control with self treatment advice, remote Web communications, and Internet-based information. We determined quality adjusted life years (QALYs) as measured by the EuroQol-5D and costs for health care use and absenteeism. We performed a detailed cost price analysis for the primary intervention. QALYs did not statistically significantly differ between the Internet group and usual care: difference 0.024 (95% CI, 0.016 to 0.065). Costs of the Internet-based intervention were $254 (95% CI, $243 to $265) during the period of 1 year. From a societal perspective, the cost difference was $641 (95% CI, $-1957 to $3240). From a health care perspective, the cost difference was $37 (95% CI, $-874 to $950). At a willingness-to-pay of $50,000 per QALY, the probability that Internet-based self-management was cost effective compared to usual care was 62% and 82% from a societal and health care perspective, respectively. CONCLUSIONS: Internet-based self-management of asthma can be as effective as current asthma care and costs are similar. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79864465. PMID- 22096524 TI - Evidence for more than one Parkinson's disease-associated variant within the HLA region. AB - Parkinson's disease (PD) was recently found to be associated with HLA in a genome wide association study (GWAS). Follow-up GWAS's replicated the PD-HLA association but their top hits differ. Do the different hits tag the same locus or is there more than one PD-associated variant within HLA? We show that the top GWAS hits are not correlated with each other (0.00<=r(2)<=0.15). Using our GWAS (2000 cases, 1986 controls) we conducted step-wise conditional analysis on 107 SNPs with P<10(-3) for PD-association; 103 dropped-out, four remained significant. Each SNP, when conditioned on the other three, yielded P(SNP1) = 5*10(-4), P(SNP2) = 5*10(-4), P(SNP3) = 4*10(-3) and P(SNP4) = 0.025. The four SNPs were not correlated (0.01<=r(2)<=0.20). Haplotype analysis (excluding rare SNP2) revealed increasing PD risk with increasing risk alleles from OR = 1.27, P = 5*10(-3) for one risk allele to OR = 1.65, P = 4*10(-8) for three. Using additional 843 cases and 856 controls we replicated the independent effects of SNP1 (P(conditioned-on-SNP4) = 0.04) and SNP4 (P(conditioned-on-SNP1) = 0.04); SNP2 and SNP3 could not be replicated. In pooled GWAS and replication, SNP1 had OR(conditioned-on-SNP4) = 1.23, P(conditioned-on-SNP4) = 6*10(-7); SNP4 had OR(conditioned-on-SNP1) = 1.18, P(conditioned-on-SNP1) = 3*10(-3); and the haplotype with both risk alleles had OR = 1.48, P = 2*10(-12). Genotypic OR increased with the number of risk alleles an individual possessed up to OR = 1.94, P = 2*10(-11) for individuals who were homozygous for the risk allele at both SNP1 and SNP4. SNP1 is a variant in HLA-DRA and is associated with HLA-DRA, DRB5 and DQA2 gene expression. SNP4 is correlated (r(2) = 0.95) with variants that are associated with HLA-DQA2 expression, and with the top HLA SNP from the IPDGC GWAS (r(2) = 0.60). Our findings suggest more than one PD-HLA association; either different alleles of the same gene, or separate loci. PMID- 22096525 TI - Effect of protein kinase C delta (PKC-delta) inhibition on the transcriptome of normal and systemic sclerosis human dermal fibroblasts in vitro. AB - Previous studies demonstrated that protein kinase C- delta (PKC-delta) inhibition with the selective inhibitor, rottlerin, resulted in potent downregulation of type I collagen expression and production in normal human dermal fibroblasts and abrogated the exaggerated type I collagen production and expression in fibroblasts cultured from affected skin from patients with the fibrosing disorder systemic sclerosis (SSc). To elucidate the mechanisms involved in the ability of PKC-delta to regulate collagen production in fibroblasts, we examined the effects of PKC-delta inhibition on the transcriptome of normal and SSc human dermal fibroblasts. Normal and SSc human dermal fibroblasts were incubated with rottlerin (5 uM), and their gene expression was analyzed by microarrays. Pathway analysis and gene ontology analysis of differentially expressed genes in each comparison were performed. Identification of significantly overrepresented transcriptional regulatory elements (TREs) was performed using the Promoter Analysis and Interaction Network Toolset (PAINT) program. PKC-delta activity was also inhibited using RNA interference (siRNA) and by treating fibroblasts with a specific PKC-delta inhibitory cell permeable peptide. Differential gene expression of 20 genes was confirmed using real time PCR. PKC-delta inhibition caused a profound change in the transcriptome of normal and SSc human dermal fibroblasts in vitro. Pathway and gene ontology analysis identified multiple cellular and organismal pathways affected by PKC-delta inhibition. Furthermore, both pathway and PAINT analyses indicated that the transcription factor NFkappaB played an important role in the transcriptome changes induced by PKC-delta inhibition. Multiple genes involved in the degradation of the extracellular matrix components were significantly reduced in SSc fibroblasts and their expression was increased by PKC-delta inhibition. These results indicate that isoform-specific inhibition of PKC-delta profibrotic effects may represent a novel therapeutic approach for SSc and other fibrotic diseases. PMID- 22096526 TI - Bmi1 is expressed in postnatal myogenic satellite cells, controls their maintenance and plays an essential role in repeated muscle regeneration. AB - Satellite cells are the resident stem cell population of the adult mammalian skeletal muscle and they play a crucial role in its homeostasis and in its regenerative capacity after injury. We show here that the Polycomb group (PcG) gene Bmi1 is expressed in both the Pax7 positive (+)/Myf5 negative (-) stem cell population as well as the Pax7+/Myf5+ committed myogenic progenitor population. Depletion of Pax7+/Myf5- satellite cells with reciprocal increase in Pax7+/Myf5+ as well as MyoD positive (+) cells is seen in Bmi1-/- mice leading to reduced postnatal muscle fiber size and impaired regeneration upon injury. Bmi1-/- satellite cells have a reduced proliferative capacity and fail to re-enter the cell cycle when stimulated by high serum conditions in vitro, in keeping with a cell intrinsic defect. Thus, both the in vivo and in vitro results suggest that Bmi1 plays a crucial role in the maintenance of the stem cell pool in postnatal skeletal muscle and is essential for efficient muscle regeneration after injury especially after repeated muscle injury. PMID- 22096528 TI - Structural-functional characterization and physiological significance of ferredoxin-NADP reductase from Xanthomonas axonopodis pv. citri. AB - Xanthomonas axonopodis pv. citri is a phytopathogen bacterium that causes severe citrus canker disease. Similar to other phytopathogens, after infection by this bacterium, plants trigger a defense mechanism that produces reactive oxygen species. Ferredoxin-NADP(+) reductases (FNRs) are redox flavoenzymes that participate in several metabolic functions, including the response to reactive oxygen species. Xanthomonas axonopodis pv. citri has a gene (fpr) that encodes for a FNR (Xac-FNR) that belongs to the subclass I bacterial FNRs. The aim of this work was to search for the physiological role of this enzyme and to characterize its structural and functional properties. The functionality of Xac FNR was tested by cross-complementation of a FNR knockout Escherichia coli strain, which exhibit high susceptibility to agents that produce an abnormal accumulation of (*)O(2)(-). Xac-FNR was able to substitute for the FNR in E. coli in its antioxidant role. The expression of fpr in X. axonopodis pv. citri was assessed using semiquantitative RT-PCR and Western blot analysis. A 2.2-fold induction was observed in the presence of the superoxide-generating agents methyl viologen and 2,3-dimethoxy-1,4-naphthoquinone. Structural and functional studies showed that Xac-FNR displayed different functional features from other subclass I bacterial FNRs. Our analyses suggest that these differences may be due to the unusual carboxy-terminal region. We propose a further classification of subclass I bacterial FNRs, which is useful to determine the nature of their ferredoxin redox partners. Using sequence analysis, we identified a ferredoxin (XAC1762) as a potential substrate of Xac-FNR. The purified ferredoxin protein displayed the typical broad UV-visible spectrum of [4Fe-4S] clusters and was able to function as substrate of Xac-FNR in the cytochrome c reductase activity. Our results suggest that Xac-FNR is involved in the oxidative stress response of Xanthomonas axonopodis pv. citri and performs its biological function most likely through the interaction with ferredoxin XAC1762. PMID- 22096527 TI - Whole-genome comparison of two Campylobacter jejuni isolates of the same sequence type reveals multiple loci of different ancestral lineage. AB - Campylobacter jejuni ST-474 is the most important human enteric pathogen in New Zealand, and yet this genotype is rarely found elsewhere in the world. Insight into the evolution of this organism was gained by a whole genome comparison of two ST-474, flaA SVR-14 isolates and other available C. jejuni isolates and genomes. The two isolates were collected from different sources, human (H22082) and retail poultry (P110b), at the same time and from the same geographical location. Solexa sequencing of each isolate resulted in ~1.659 Mb (H22082) and ~1.656 Mb (P110b) of assembled sequences within 28 (H22082) and 29 (P110b) contigs. We analysed 1502 genes for which we had sequences within both ST-474 isolates and within at least one of 11 C. jejuni reference genomes. Although 94.5% of genes were identical between the two ST-474 isolates, we identified 83 genes that differed by at least one nucleotide, including 55 genes with non synonymous substitutions. These covered 101 kb and contained 672 point differences. We inferred that 22 (3.3%) of these differences were due to mutation and 650 (96.7%) were imported via recombination. Our analysis estimated 38 recombinant breakpoints within these 83 genes, which correspond to recombination events affecting at least 19 loci regions and gives a tract length estimate of ~2 kb. This includes a ~12 kb region displaying non-homologous recombination in one of the ST-474 genomes, with the insertion of two genes, including ykgC, a putative oxidoreductase, and a conserved hypothetical protein of unknown function. Furthermore, our analysis indicates that the source of this recombined DNA is more likely to have come from C. jejuni strains that are more closely related to ST-474. This suggests that the rates of recombination and mutation are similar in order of magnitude, but that recombination has been much more important for generating divergence between the two ST-474 isolates. PMID- 22096529 TI - Resource wars and conflict ivory: the impact of civil conflict on elephants in the Democratic Republic of Congo--the case of the Okapi Reserve. AB - Human conflict generally has substantial negative impacts on wildlife and conservation. The recent civil war (1995-2006) in the Democratic Republic of Congo (DRC) resulted in a significant loss of wildlife, including elephants, due to institutional collapse, lawlessness and unbridled exploitation of natural resources such as minerals, wood, ivory and bushmeat. We used data from distance sampling surveys conducted before and after the war in a protected forest, the Okapi Faunal Reserve, to document changes in elephant abundance and distribution. We employed Generalized Additive Models to relate changes in elephant distribution to human and environmental factors. Populations declined by nearly fifty percent coinciding with a major increase in elephant poaching as indicated by reports of ivory trade during the war. Our results suggest that humans influenced elephant distribution far more than habitat, both before and after the war, but post-war models explained more of the variation. Elephant abundance declined more, closer to the park boundary and to areas of intense human activity. After the war, elephant densities were relatively higher in the centre of the park where they were better protected, suggesting that this area may have acted as a refuge. In other sites in Eastern DRC, where no protection was provided, elephants were even more decimated. Post-war dynamics, such as weakened institutions, human movements and availability of weapons, continue to affect elephants. Survival of remaining populations and recovery will be determined by these persistent factors and by new threats associated with growing human populations and exploitation of natural resources. Prioritizing wildlife protection, curbing illegal trade in ivory and bushmeat, and strengthening national institutions and organizations in charge of conservation will be crucial to counter these threats. PMID- 22096530 TI - Insufficiently defined genetic background confounds phenotypes in transgenic studies as exemplified by malaria infection in Tlr9 knockout mice. AB - The use of genetically modified mice, i.e. transgenic as well as gene knockout (KO) and knock-in mice, has become an established tool to study gene function in many animal models for human diseases. However, a gene functions in a particular genomic context. This implies the importance of a well-defined homogenous genetic background for the analysis and interpretation of phenotypes associated with genetic mutations. By studying a Plasmodium chabaudi chabaudi AS (PcAS) malaria infection in mice bearing a TLR9 null mutation, we found an increased susceptibility to infection, i.e. higher parasitemia levels and increased mortality. However, this was not triggered by the deficient TLR9 gene itself. Instead, this disease phenotype was dependent on the heterogeneous genetic background of the mice, which appeared insufficiently defined as determined by single nucleotide polymorphism (SNP) analysis. Hence, it is of critical importance to study gene KO phenotypes on a homogenous genetic background identical to that of their wild type (WT) control counterparts. In particular, to avoid problems related to an insufficiently defined genetic background, we advocate that for each study involving genetically modified mice, at least a detailed description of the origin and genetic background of both the WT control and the altered strain of mice is essential. PMID- 22096531 TI - Loss of sphingosine kinase 1/S1P signaling impairs cell growth and survival of neurons and progenitor cells in the developing sensory ganglia. AB - BACKGROUND: Lysophospholipids such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are important signaling molecules that can regulate a wide range of cellular responses. We discovered that Sphingosine kinase 1 (Sphk1), a key enzyme that converts sphingosine to S1P, is expressed in neurons and progenitor cells in nascent trigeminal and dorsal root ganglia during mouse embryogenesis. METHODS AND FINDINGS: Sphk1 null mouse embryos do not display overt deficits owing to compensation by Sphk2. Thus, we analyzed embryos that are deficient in both Sphk1 and Sphk2 (which essentially eliminates S1P function) in order to investigate the role(s) of Sphk1 during sensory ganglia formation. While animals lacking 1-3 alleles of Sphk1 and Sphk2 had no obvious phenotype, embryos without both genes displayed clear developmental defects. The complete absence of Sphk1 and Sphk2 resulted in trigeminal and dorsal root ganglia with fewer neurons and progenitor cells. The profound loss in cell number could be attributed to a decrease in cell proliferation as well as an increase in apoptosis. Furthermore, Sphk1/2 double mutants displayed an overall reduction in other sphingolipids as well as an imbalance of S1P/sphingosine and S1P/ceramide ratio, thereby favoring cell death and reducing cell growth. CONCLUSIONS: Together, these results provide strong in vivo evidence that sphingosine kinase/S1P signaling plays an important role in regulating early events during development of sensory ganglia. PMID- 22096532 TI - A convenient model of severe, high incidence autoimmune gastritis caused by polyclonal effector T cells and without perturbation of regulatory T cells. AB - Autoimmune gastritis results from the breakdown of T cell tolerance to the gastric H(+)/K(+) ATPase. The gastric H(+)/K(+) ATPase is responsible for the acidification of gastric juice and consists of an alpha subunit (H/Kalpha) and a beta subunit (H/Kbeta). Here we show that CD4(+) T cells from H/Kalpha-deficient mice (H/Kalpha(-/-)) are highly pathogenic and autoimmune gastritis can be induced in sublethally irradiated wildtype mice by adoptive transfer of unfractionated CD4(+) T cells from H/Kalpha(-/-) mice. All recipient mice consistently developed the most severe form of autoimmune gastritis 8 weeks after the transfer, featuring hypertrophy of the gastric mucosa, complete depletion of the parietal and zymogenic cells, and presence of autoantibodies to H(+)/K(+) ATPase in the serum. Furthermore, we demonstrated that the disease significantly affected stomach weight and stomach pH of recipient mice. Depletion of parietal cells in this disease model required the presence of both H/Kalpha and H/Kbeta since transfer of H/Kalpha(-/-) CD4(+) T cells did not result in depletion of parietal cells in H/Kalpha(-/-) or H/Kbeta(-/-) recipient mice. The consistency of disease severity, the use of polyclonal T cells and a specific T cell response to the gastric autoantigen make this an ideal disease model for the study of many aspects of organ-specific autoimmunity including prevention and treatment of the disease. PMID- 22096533 TI - Justice blocks and predictability of U.S. Supreme Court votes. AB - Successful attempts to predict judges' votes shed light into how legal decisions are made and, ultimately, into the behavior and evolution of the judiciary. Here, we investigate to what extent it is possible to make predictions of a justice's vote based on the other justices' votes in the same case. For our predictions, we use models and methods that have been developed to uncover hidden associations between actors in complex social networks. We show that these methods are more accurate at predicting justice's votes than forecasts made by legal experts and by algorithms that take into consideration the content of the cases. We argue that, within our framework, high predictability is a quantitative proxy for stable justice (and case) blocks, which probably reflect stable a priori attitudes toward the law. We find that U.S. Supreme Court justice votes are more predictable than one would expect from an ideal court composed of perfectly independent justices. Deviations from ideal behavior are most apparent in divided 5-4 decisions, where justice blocks seem to be most stable. Moreover, we find evidence that justice predictability decreased during the 50-year period spanning from the Warren Court to the Rehnquist Court, and that aggregate court predictability has been significantly lower during Democratic presidencies. More broadly, our results show that it is possible to use methods developed for the analysis of complex social networks to quantitatively investigate historical questions related to political decision-making. PMID- 22096534 TI - Moth wing scales slightly increase the absorbance of bat echolocation calls. AB - Coevolutionary arms races between predators and prey can lead to a diverse range of foraging and defense strategies, such as countermeasures between nocturnal insects and echolocating bats. Here, we show how the fine structure of wing scales may help moths by slightly increasing sound absorbance at frequencies typically used in bat echolocation. Using four widespread species of moths and butterflies, we found that moth scales are composed of honeycomb-like hollows similar to sound-absorbing material, but these were absent from butterfly scales. Micro-reverberation chamber experiments revealed that moth wings were more absorbent at the frequencies emitted by many echolocating bats (40-60 kHz) than butterfly wings. Furthermore, moth wings lost absorbance at these frequencies when scales were removed, which suggests that some moths have evolved stealth tactics to reduce their conspicuousness to echolocating bats. Although the benefits to moths are relatively small in terms of reducing their target strengths, scales may nonetheless confer survival advantages by reducing the detection distances of moths by bats by 5-6%. PMID- 22096535 TI - Kidney bean: a major sensitizer among legumes in asthma and rhinitis patients from India. AB - BACKGROUND: The prevalence of IgE mediated food allergies has increased over the last two decades. Food allergy has been reported to be fatal in highly sensitive individuals. Legumes are important food allergens but their prevalence may vary among different populations. The present study identifies sensitization to common legumes among Indian population, characterizes allergens of kidney bean and establishes its cross reactivity with other legumes. METHODOLOGY: Patients (n = 355) with history of legume allergy were skin prick tested (SPT) with 10 legumes. Specific IgE (sIgE) and total IgE were estimated in sera by enzyme-linked immunosorbent assay. Characterization of kidney bean allergens and their cross reactivity was investigated by immunobiochemical methods. Identification of major allergens of kidney bean was carried out by mass spectrometry. PRINCIPAL FINDINGS: Kidney bean exhibited sensitization in 78 (22.0%) patients followed by chickpea 65 (18.0%) and peanut 53 (15%). SPT positive patients depicted significantly elevated sIgE levels against different legumes (r = 0.85, p<0.0001). Sera from 30 kidney bean sensitive individuals exhibited basophil histamine release (16-54%) which significantly correlated with their SPT (r = 0.83, p<0.0001) and sIgE (r = 0.99, p<0.0001). Kidney bean showed eight major allergens of 58, 50, 45, 42, 40, 37, 34 and 18 kDa on immunoblot and required 67.3+/-2.51 ng of homologous protein for 50% IgE inhibition. Inhibition assays revealed extensive cross reactivity among kidney bean, peanut, black gram and pigeon pea. nLC-MS/MS analysis identified four allergens of kidney bean showing significant matches with known proteins namely lectin (phytohemagglutinin), phaseolin, alpha-amylase inhibitor precursor and group 3 late embryogenesis abundant protein. CONCLUSION/SIGNIFICANCE: Among legumes, kidney bean followed by chick pea and peanut are the major allergic triggers in asthma and rhinitis patients in India. Kidney bean showed eight major allergens and cross reacted with other legumes. A combination of SPT, sIgE and histamine release assay is helpful in allergy diagnosis. PMID- 22096536 TI - Xenopus reduced folate carrier regulates neural crest development epigenetically. AB - Folic acid deficiency during pregnancy causes birth neurocristopathic malformations resulting from aberrant development of neural crest cells. The Reduced folate carrier (RFC) is a membrane-bound receptor for facilitating transfer of reduced folate into the cells. RFC knockout mice are embryonic lethal and develop multiple malformations, including neurocristopathies. Here we show that XRFC is specifically expressed in neural crest tissues in Xenopus embryos and knockdown of XRFC by specific morpholino results in severe neurocristopathies. Inhibition of RFC blocked the expression of a series of neural crest marker genes while overexpression of RFC or injection of 5 methyltetrahydrofolate expanded the neural crest territories. In animal cap assays, knockdown of RFC dramatically reduced the mono- and trimethyl-Histone3-K4 levels and co-injection of the lysine methyltransferase hMLL1 largely rescued the XRFC morpholino phenotype. Our data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications. PMID- 22096537 TI - Functional organization of hsp70 cluster in camel (Camelus dromedarius) and other mammals. AB - Heat shock protein 70 (Hsp70) is a molecular chaperone providing tolerance to heat and other challenges at the cellular and organismal levels. We sequenced a genomic cluster containing three hsp70 family genes linked with major histocompatibility complex (MHC) class III region from an extremely heat tolerant animal, camel (Camelus dromedarius). Two hsp70 family genes comprising the cluster contain heat shock elements (HSEs), while the third gene lacks HSEs and should not be induced by heat shock. Comparison of the camel hsp70 cluster with the corresponding regions from several mammalian species revealed similar organization of genes forming the cluster. Specifically, the two heat inducible hsp70 genes are arranged in tandem, while the third constitutively expressed hsp70 family member is present in inverted orientation. Comparison of regulatory regions of hsp70 genes from camel and other mammals demonstrates that transcription factor matches with highest significance are located in the highly conserved 250-bp upstream region and correspond to HSEs followed by NF-Y and Sp1 binding sites. The high degree of sequence conservation leaves little room for putative camel-specific regulatory elements. Surprisingly, RT-PCR and 5'/3'-RACE analysis demonstrated that all three hsp70 genes are expressed in camel's muscle and blood cells not only after heat shock, but under normal physiological conditions as well, and may account for tolerance of camel cells to extreme environmental conditions. A high degree of evolutionary conservation observed for the hsp70 cluster always linked with MHC locus in mammals suggests an important role of such organization for coordinated functioning of these vital genes. PMID- 22096538 TI - Distinct expression patterns of CD69 in mucosal and systemic lymphoid tissues in primary SIV infection of rhesus macaques. AB - Although the intestinal tract plays a major role in early human immunodeficiency virus (HIV) infection, the role of immune activation and viral replication in intestinal tissues is not completely understood. Further, increasing evidence suggests the early leukocyte activation antigen CD69 may be involved in the development or regulation of important T cell subsets, as well as a major regulatory molecule of immune responses. Using the simian immunodeficiency virus (SIV) rhesus macaque model, we compared expression of CD69 on T cells from the intestine, spleen, lymph nodes, and blood of normal and SIV-infected macaques throughout infection. In uninfected macaques, the majority of intestinal lamina propria CD4+ T cells had a memory (CD95+) phenotype and co-expressed CD69, and essentially all intestinal CCR5+ cells co-expressed CD69. In contrast, systemic lymphoid tissues had far fewer CD69+ T cells, and many had a naive phenotype. Further, marked, selective depletion of intestinal CD4+CD69+ T cells occurred in early SIV infection, and this depletion persisted throughout infection. Markedly increased levels of CD8+CD69+ T cells were detected after SIV infection in virtually all tissues, including the intestine. Further, confocal microscopy demonstrated selective, productive infection of CD3+CD69+ T cells in the intestine in early infection. Combined, these results indicate CD69+CD4+ T cells are a major early target for viral infection, and their rapid loss by direct infection may have profound effects on intestinal immune regulation in HIV infected patients. PMID- 22096539 TI - A secreted form of the asialoglycoprotein receptor, sH2a, as a novel potential noninvasive marker for liver fibrosis. AB - BACKGROUND AND AIM: The human asialoglycoprotein receptor is a membrane heterooligomer expressed exclusively in hepatocytes. A soluble secreted form, sH2a, arises, not by shedding at the cell surface, but by intracellular cleavage of its membrane-bound precursor, which is encoded by an alternatively spliced form of the receptor H2 subunit. Here we determined and report that sH2a, present at constant levels in serum from healthy individuals is altered upon liver fibrosis, reflecting the status of hepatocyte function. METHODS: We measured sH2a levels in serum using a monoclonal antibody and an ELISA assay that we developed, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of 44 hepatitis C patients, which had METAVIR-scored biopsies, with 28 healthy individuals. RESULTS: sH2a levels varied minimally for the healthy individuals (150+/-21 ng/ml), whereas the levels deviated from this normal range increasingly in correlation with fibrosis stage. A simple algorithm combining sH2a levels with those of alanine aminotransferase allowed prediction of fibrosis stage, with a very high area under the ROC curve of 0.86. CONCLUSIONS: sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function. PMID- 22096540 TI - The evaluation of the oxidative stress parameters in patients with primary angle closure glaucoma. AB - OBJECTIVE: To clarify the presence of oxidative stress in patients with primary angle-closure glaucoma (PACG) and to investigate the relationship between oxidative stress and PACG. METHODS: Fifty patients with primary angle-closure glaucoma and fifty healthy controls of matched age and gender were included in the study prospectively. Serum samples were obtained to detect the oxidation degradation products malondialdehyde (MDA), conjugated diene (CD), 4 hydroxynonenal (4-HNE), advanced oxidation protein products (AOPP), protein carbonyl (PC), ischemia-modified albumin (IMA) and 8-hydroxydeoxyguanosin (8 OHdG). RESULTS: The concentration of MDA and CD in PACG patients was significantly higher than those of the control subjects (P<0.05, P<0.01). The serum 4-HNE concentrations were increased in PACG patients, but the differences with those of the healthy controls were not statistically significant. Compared to normal subjects, there was significant higher in serum AOPP and PC in PACG patients (P<0.01). PACG patients had higher levels of 8-OHdG in serum with respect to the comparative group of normal subjects (P<0.01). When plasma IMA levels in the PACG group were compared with those in the control group, significant increases in IMA were observed in the former (P<0.05). CONCLUSIONS: Our study demonstrated that IMA is a new biomarker available for assessing oxidative stress in PCAG. Oxidative stress is an important risk factor in the development of primary angle-closure glaucoma. Increased levels of oxidative stress products may be associated with primary angle-closure glaucoma. PMID- 22096541 TI - Phosphatidylinositol (4,5) bisphosphate controls T cell activation by regulating T cell rigidity and organization. AB - Here we investigate the role of Phosphatidylinositol (4,5) bisphosphate (PIP(2)) in the physiological activation of primary murine T cells by antigen presenting cells (APC) by addressing two principal challenges in PIP(2) biology. First, PIP(2) is a regulator of cytoskeletal dynamics and a substrate for second messenger generation. The relative importance of these two processes needs to be determined. Second, PIP(2) is turned over by multiple biosynthetic and metabolizing enzymes. The joint effect of these enzymes on PIP(2) distributions needs to be determined with resolution in time and space. We found that T cells express four isoforms of the principal PIP(2)-generating enzyme phosphatidylinositol 4-phosphate 5-kinase (PIP5K) with distinct spatial and temporal characteristics. In the context of a larger systems analysis of T cell signaling, these data identify the T cell/APC interface and the T cell distal pole as sites of differential PIP(2) turnover. Overexpression of different PIP5K isoforms, as corroborated by knock down and PIP(2) blockade, yielded an increase in PIP(2) levels combined with isoform-specific changes in the spatiotemporal distributions of accessible PIP(2). It rigidified the T cell, likely by impairing the inactivation of Ezrin Moesin Radixin, delayed and diminished the clustering of the T cell receptor at the cellular interface, reduced the efficiency of T cell proximal signaling and IL-2 secretion. These effects were consistently more severe for distal PIP5K isoforms. Thus spatially constrained cytoskeletal roles of PIP(2) in the control of T cell rigidity and spatiotemporal organization dominate the effects of PIP(2) on T cell activation. PMID- 22096542 TI - An antibody to de-N-acetyl sialic acid containing-polysialic acid identifies an intracellular antigen and induces apoptosis in human cancer cell lines. AB - Polysialic acid (PSA), an alpha2,8-linked homopolymer of N-acetylneuraminic acid (Neu5Ac), is developmentally regulated and its expression is thought to be restricted to a few tissues in adults. Recently, we showed that two human pathogens expressed a derivative of PSA containing de-N-acetyl sialic acid residues (NeuPSA). Here we show that an epitope identified by the anti-NeuPSA monoclonal antibody, SEAM 3 (SEAM 3-reactive antigen or S3RA), is expressed in human melanomas, and also intracellularly in a human melanoma cell line (SK-MEL 28), a human T cell leukemia cell line (Jurkat), and two neuroblastoma cell lines (CHP-134 and SH-SY5Y). SEAM 3 binding induced apoptosis in the four cell lines tested. The unusual intracellular distribution of S3RA was similar to that described for the PSA polysialyltransferases, STX and PST, which are also expressed in the four cell lines used here. Interestingly, suppression of PST mRNA expression by transfection of SK-MEL-28 cells with PST-specific short interfering RNA (siRNA) resulted in decreased SEAM 3 binding. The results suggest further studies of the utility of antibodies such as SEAM 3 as therapeutic agents for certain malignancies. PMID- 22096543 TI - Dengue reporter virus particles for measuring neutralizing antibodies against each of the four dengue serotypes. AB - The lack of reliable, high-throughput tools for characterizing anti-dengue virus (DENV) antibodies in large numbers of serum samples has been an obstacle in understanding the impact of neutralizing antibodies on disease progression and vaccine efficacy. A reporter system using pseudoinfectious DENV reporter virus particles (RVPs) was previously developed by others to facilitate the genetic manipulation and biological characterization of DENV virions. In the current study, we demonstrate the diagnostic utility of DENV RVPs for measuring neutralizing antibodies in human serum samples against all four DENV serotypes, with attention to the suitability of DENV RVPs for large-scale, long-term studies. DENV RVPs used against human sera yielded serotype-specific responses and reproducible neutralization titers that were in statistical agreement with Plaque Reduction Neutralization Test (PRNT) results. DENV RVPs were also used to measure neutralization titers against the four DENV serotypes in a panel of human sera from a clinical study of dengue patients. The high-throughput capability, stability, rapidity, and reproducibility of assays using DENV RVPs offer advantages for detecting immune responses that can be applied to large-scale clinical studies of DENV infection and vaccination. PMID- 22096544 TI - Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells. AB - BACKGROUND: Scopolamine is a well-known cholinergic antagonist that causes amnesia in human and animal models. Scopolamine-induced amnesia in rodent models has been widely used to understand the molecular, biochemical, behavioral changes, and to delineate therapeutic targets of memory impairment. Although this has been linked to the decrease in central cholinergic neuronal activity following the blockade of muscarinic receptors, the underlying molecular and cellular mechanism(s) particularly the effect on neuroplasticity remains elusive. In the present study, we have investigated (i) the effects of scopolamine on the molecules involved in neuronal and glial plasticity both in vivo and in vitro and (ii) their recovery by alcoholic extract of Ashwagandha leaves (i-Extract). METHODOLOGY/PRINCIPAL FINDINGS: As a drug model, scopolamine hydrobromide was administered intraperitoneally to mice and its effect on the brain function was determined by molecular analyses. The results showed that the scopolamine caused downregulation of the expression of BDNF and GFAP in dose and time dependent manner, and these effects were markedly attenuated in response to i-Extract treatment. Similar to our observations in animal model system, we found that the scopolamine induced cytotoxicity in IMR32 neuronal and C6 glioma cells. It was associated with downregulation of neuronal cell markers NF-H, MAP2, PSD-95, GAP 43 and glial cell marker GFAP and with upregulation of DNA damage--gammaH2AX and oxidative stress--ROS markers. Furthermore, these molecules showed recovery when cells were treated with i-Extract or its purified component, withanone. CONCLUSION: Our study suggested that besides cholinergic blockade, scopolamine induced memory loss may be associated with oxidative stress and Ashwagandha i Extract, and withanone may serve as potential preventive and therapeutic agents for neurodegenerative disorders and hence warrant further molecular analyses. PMID- 22096545 TI - Acidocalcisomes as calcium- and polyphosphate-storage compartments during embryogenesis of the insect Rhodnius prolixus Stahl. AB - BACKGROUND: The yolk of insect eggs is a cellular domain specialized in the storage of reserve components for embryo development. The reserve macromolecules are stored in different organelles and their interactions with the embryo cells are mostly unknown. Acidocalcisomes are lysosome-related organelles characterized by their acidic nature, high electron density and large content of polyphosphate bound to several cations. In this work, we report the presence of acidocalcisome like organelles in eggs of the insect vector Rhodnius prolixus. METHODOLOGY/PRINCIPAL FINDINGS: Characterization of the elemental composition of electron-dense vesicles by electron probe X-ray microanalysis revealed a composition similar to that previously described for acidocalcisomes. Following subcellular fractionation experiments, fractions enriched in acidocalcisomes were obtained and characterized. Immunofluorescence showed that polyphosphate polymers and the vacuolar proton translocating pyrophosphatase (V-H(+)-PPase, considered as a marker for acidocalcisomes) are found in the same vesicles and that these organelles are mainly localized in the egg cortex. Polyphosphate quantification showed that acidocalcisomes contain a significant amount of polyphosphate detected at day-0 eggs. Elemental analyses of the egg fractions showed that 24.5+/-0.65% of the egg calcium are also stored in such organelles. During embryogenesis, incubation of acidocalcisomes with acridine orange showed that these organelles are acidified at day-3 (coinciding with the period of yolk mobilization) and polyphosphate quantification showed that the levels of polyphosphate tend to decrease during early embryogenesis, being approximately 30% lower at day-3 compared to day-0 eggs. CONCLUSIONS: We found that acidocalcisomes are present in the eggs and are the main storage compartments of polyphosphate and calcium in the egg yolk. As such components have been shown to be involved in a series of dynamic events that may control embryo growth, results reveal the potential involvement of a novel organelle in the storage and mobilization of inorganic elements to the embryo cells. PMID- 22096546 TI - Suppression of expression of heat shock protein 70 by gefitinib and its contribution to pulmonary fibrosis. AB - Drug-induced interstitial lung disease (ILD), particularly pulmonary fibrosis, is of serious clinical concern. Gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), is beneficial as a drug for treating non small cell lung cancer; however, this drug induces ILD and the molecular mechanisms underpinning this condition remain unclear. We recently reported that expression of heat shock protein 70 (HSP70) protects against bleomycin-induced pulmonary fibrosis, an animal model of pulmonary fibrosis. In this study, we have examined the effects of drugs known to induce ILD clinically on the expression of HSP70 in cultured lung epithelial cells and have found that gefitinib has a suppressive effect. Results of a luciferase reporter assay, pulse-labelling analysis of protein and experiments using an inhibitor of translation or transcription suggest that gefitinib suppresses the expression of HSP70 at the level of translation. Furthermore, the results of experiments with siRNA for Dicer1, an enzyme responsible for synthesis of microRNA, and real-time RT-PCR analysis suggest that some microRNAs are involved in the gefitinib-induced translational inhibition of HSP70. Mutations in the EGFR affect the concentration of gefitinib required for suppressing the expression of HSP70. These results suggest that gefitinib suppresses the translation of HSP70 through an EGFR- and microRNA-mediated mechanism. In vivo, while oral administration of gefitinib suppressed the pulmonary expression of HSP70 and exacerbated bleomycin-induced pulmonary fibrosis in wild-type mice, these effects were not as distinct in transgenic mice expressing HSP70. Furthermore, oral co-administration of geranylgeranylacetone (GGA), an inducer of HSP70, suppressed gefitinib-induced exacerbation of bleomycin-induced pulmonary fibrosis. Taken together, these findings suggest that gefitinib-induced exacerbation of bleomycin-induced pulmonary fibrosis is mediated by suppression of pulmonary expression of HSP70 and that an inducer of HSP70 expression, such as GGA, may be therapeutically beneficial for the treatment of gefitinib-induced pulmonary fibrosis. PMID- 22096547 TI - Antibiotic resistance gene abundances correlate with metal and geochemical conditions in archived Scottish soils. AB - The vast majority of antibiotic resistant genes (ARG) acquired by human pathogens have originated from the natural environment. Therefore, understanding factors that influence intrinsic levels of ARG in the environment could be epidemiologically significant. The selection for metal resistance often promotes AR in exposed organisms; however, the relationship between metal levels in nature and the intrinsic presence of ARG has not been fully assessed. Here, we quantified, using qPCR, the abundance of eleven ARG and compared their levels with geochemical conditions in randomly selected soils from a Scottish archive. Many ARG positively correlated with soil copper levels, with approximately half being highly significant (p<0.05); whereas chromium, nickel, lead, and iron also significantly correlated with specific ARG. Results show that geochemical metal conditions innately influence the potential for AR in soil. We suggest soil geochemical data might be used to estimate baseline gene presence on local, regional and global scales within epidemiological risk studies related to AR transmission from the environment. PMID- 22096548 TI - In vitro recombination of non-homologous genes can result in gene fusions that confer a switching phenotype to cells. AB - Regulation of protein activity is central to the complexity of life. The ability to regulate protein activity through exogenously added molecules has biotechnological/biomedical applications and offers tools for basic science. Such regulation can be achieved by establishing a means to modulate the specific activity of the protein (i.e. allostery). An alternative strategy for intracellular regulation of protein activity is to control the amount of protein through effects on its production, accumulation, and degradation. We have previously demonstrated that the non-homologous recombination of the genes encoding maltose binding protein (MBP) and TEM1 beta-lactamase (BLA) can result in fusion proteins in which beta-lactamase enzyme activity is allosterically regulated by maltose. Here, through use of a two-tiered genetic selection scheme, we demonstrate that such recombination can result in genes that confer maltose dependent resistance to beta-lactam even though they do not encode allosteric enzymes. These 'phenotypic switch' genes encode fusion proteins whose accumulation is a result of a specific interaction with maltose. Phenotypic switches represent an important class of proteins for basic science and biotechnological applications in vivo. PMID- 22096549 TI - The structural basis of localizing polo-like kinase to the flagellum attachment zone in Trypanosoma brucei. AB - The polo-like kinase in the deep branching eukaryote Trypanosoma brucei (TbPlk) has many unique features. Unlike all the other polo-like kinases known to associate with the nucleus and controlling both mitosis and cytokinesis, TbPlk localizes to the flagellum attachment zone (FAZ) and regulates only cytokinesis in T. brucei. TbPlk was, however, previously found capable of complementing all the multiple Plk (Cdc5) functions in Saccharomyces cerevisiae, indicating that it has acquired all the functions of Cdc5. In the present study, Cdc5 tagged with an enhanced yellow fluorescence protein (EYFP) localized exclusively in the FAZ of T. brucei, suggesting that the unusual localization and limited function of TbPlk are probably attributed to the particular environment in T. brucei cells. Structural basis for the FAZ localization of TbPlk was further investigated with TbPlk and TbPlk mutants tagged with EYFP and expressed in T. brucei. The results indicated that a kinase-inactive mutant N169A and a TbPlk mutant with the entire kinase domain (KD) deleted both localized to the FAZ. Substantial association with FAZ was also maintained when one of the two polo-boxes (PB1 or 2) or the linker region between them was deleted from TbPlk. But a deletion of both polo boxes led to a complete exclusion of the protein from FAZ. All the deletion mutants retained the kinase activity, further indicating that the TbPlk kinase function does not play a role for FAZ localization. The two polo boxes in TbPlk are most likely instrumental in localizing the protein to FAZ through potential interactions with certain FAZ structural component(s). A putative cryptic bipartite nuclear targeting signal was identified in TbPlk, which was capable of directing TbPlk into the nucleus when either the kinase activity was lost or the PB1 was deleted from the protein. PMID- 22096550 TI - Temperature-dependence of Weibel-Palade body exocytosis and cell surface dispersal of von Willebrand factor and its propolypeptide. AB - BACKGROUND: Weibel-Palade bodies (WPB) are endothelial cell (EC) specific secretory organelles containing Von Willebrand factor (VWF). The temperature dependence of Ca(2+)-driven WPB exocytosis is not known, although indirect evidence suggests that WPB exocytosis may occur at very low temperatures. Here we quantitatively analyse the temperature-dependence of Ca(2+)-driven WPB exocytosis and release of secreted VWF from the cell surface of ECs using fluorescence microscopy of cultured human ECs containing fluorescent WPBs. PRINCIPAL FINDINGS: Ca(2+)-driven WPB exocytosis occurred at all temperatures studied (7-37 degrees C). The kinetics and extent of WPB exocytosis were strongly temperature dependent: Delays in exocytosis increased from 0.92 s at 37 degrees C to 134.2 s at 7 degrees C, the maximum rate of WPB fusion decreased from 10.0+/-2.2 s(-1) (37 degrees C) to 0.80+/-0.14 s(-1) (7 degrees C) and the fractional extent of degranulation of WPBs in each cell from 67+/-3% (37 degrees C) to 3.6+/-1.3% (7 degrees C). A discrepancy was found between the reduction in Ca(2+)-driven VWF secretion and WPB exocytosis at reduced temperature; at 17 degrees C VWF secretion was reduced by 95% but WPB exocytosis by 75-80%. This discrepancy arises because VWF dispersal from sites of WPB exocytosis is largely prevented at low temperature. In contrast VWF-propolypeptide (proregion) dispersal from WPBs, although slowed, was complete within 60-120 s. Novel antibodies to the cleaved and processed proregion were characterised and used to show that secreted proregion more accurately reports the secretion of WPBs at sub-physiological temperatures than assay of VWF itself. CONCLUSIONS: We report the first quantitative analysis of the temperature-dependence of WPB exocytosis. We provide evidence; by comparison of biochemical data for VWF or proregion secretion with direct analysis of WPB exocytosis at reduced temperature, that proregion is a more reliable marker for WPB exocytosis at reduced temperature, where VWF-EC adhesion is increased. PMID- 22096551 TI - Risk behaviors and reasons for not getting tested for HIV among men who have sex with men: an online survey in Peru. AB - BACKGROUND: Men who have sex with men (MSM) account for the greatest burden of the HIV epidemic in Peru. Given that MSM are frequent users of the Internet, understanding the risk behaviors and the reasons for not getting tested among MSM who surf the Internet may improve the tailoring of future online behavioral interventions. METHODS: From October 2007 to April 2008, we conducted an online survey among users of seven Peruvian gay websites. RESULTS: We received 1,481 surveys, 1,301 of which were included in the analysis. The median age of the participants was 22.5 years (range 12-71), 67% were homosexual, and the remainder was bisexual. Of survey respondents, 49.4% had never been tested for HIV and only 11.3% were contacted in-person during the last year by peer health educators from the Peruvian Ministry of Health and NGOs. Additionally, 50.8% had unprotected anal or vaginal sex at last intercourse, and a significant percentage reported a condom broken (22.1%), slipped (16.4%) or sexual intercourse initiated without wearing a condom (39.1%). The most common reasons for not getting tested for HIV among high-risk MSM were "I fear the consequences of a positive test result" (n = 55, 34.4%), and "I don't know where I can get tested" (n = 50, 31.3%). CONCLUSIONS: A small percentage of Peruvian MSM who answered our online survey, were reached by traditional peer-based education programs. Given that among high risk MSM, fear of a positive test result and lack of awareness of places where to get tested are the most important reasons for not taking an HIV test, Internet interventions aimed at motivating HIV testing should work to reduce fear of testing and increase awareness of places that offer free HIV testing services to MSM. PMID- 22096552 TI - Next generation sequencing-based analysis of repetitive DNA in the model dioecious [corrected] plant Silene latifolia. AB - BACKGROUND: Silene latifolia is a dioecious [corrected] plant with well distinguished X and Y chromosomes that is used as a model to study sex determination and sex chromosome evolution in plants. However, efficient utilization of this species has been hampered by the lack of large-scale sequencing resources and detailed analysis of its genome composition, especially with respect to repetitive DNA, which makes up the majority of the genome. METHODOLOGY/PRINCIPAL FINDINGS: We performed low-pass 454 sequencing followed by similarity-based clustering of 454 reads in order to identify and characterize sequences of all major groups of S. latifolia repeats. Illumina sequencing data from male and female genomes were also generated and employed to quantify the genomic proportions of individual repeat families. The majority of identified repeats belonged to LTR-retrotransposons, constituting about 50% of genomic DNA, with Ty3/gypsy elements being more frequent than Ty1/copia. While there were differences between the male and female genome in the abundance of several repeat families, their overall repeat composition was highly similar. Specific localization patterns on sex chromosomes were found for several satellite repeats using in situ hybridization with probes based on k-mer frequency analysis of Illumina sequencing data. CONCLUSIONS/SIGNIFICANCE: This study provides comprehensive information about the sequence composition and abundance of repeats representing over 60% of the S. latifolia genome. The results revealed generally low divergence in repeat composition between the sex chromosomes, which is consistent with their relatively recent origin. In addition, the study generated various data resources that are available for future exploration of the S. latifolia genome. PMID- 22096553 TI - Internal colonization of Salmonella enterica serovar Typhimurium in tomato plants. AB - Several Salmonella enterica outbreaks have been traced back to contaminated tomatoes. In this study, the internalization of S. enterica Typhimurium via tomato leaves was investigated as affected by surfactants and bacterial rdar morphotype, which was reported to be important for the environmental persistence and attachment of Salmonella to plants. Surfactants, especially Silwet L-77, promoted ingress and survival of S. enterica Typhimurium in tomato leaves. In each of two experiments, 84 tomato plants were inoculated two to four times before fruiting with GFP-labeled S. enterica Typhimurium strain MAE110 (with rdar morphotype) or MAE119 (without rdar). For each inoculation, single leaflets were dipped in 10(9) CFU/ml Salmonella suspension with Silwet L-77. Inoculated and adjacent leaflets were tested for Salmonella survival for 3 weeks after each inoculation. The surface and pulp of ripe fruits produced on these plants were also examined for Salmonella. Populations of both Salmonella strains in inoculated leaflets decreased during 2 weeks after inoculation but remained unchanged (at about 10(4) CFU/g) in week 3. Populations of MAE110 were significantly higher (P<0.05) than those of MAE119 from day 3 after inoculation. In the first year, nine fruits collected from one of the 42 MAE119 inoculated plants were positive for S. enterica Typhimurium. In the second year, Salmonella was detected in adjacent non-inoculated leaves of eight tomato plants (five inoculated with strain MAE110). The pulp of 12 fruits from two plants inoculated with MAE110 was Salmonella positive (about 10(6) CFU/g). Internalization was confirmed by fluorescence and confocal laser microscopy. For the first time, convincing evidence is presented that S. enterica can move inside tomato plants grown in natural field soil and colonize fruits at high levels without inducing any symptoms, except for a slight reduction in plant growth. PMID- 22096554 TI - Origins and evolution of the HET-s prion-forming protein: searching for other amyloid-forming solenoids. AB - The HET-s prion-forming domain from the filamentous fungus Podospora anserina is gaining considerable interest since it yielded the first well-defined atomic structure of a functional amyloid fibril. This structure has been identified as a left-handed beta solenoid with a triangular hydrophobic core. To delineate the origins of the HET-s prion-forming protein and to discover other amyloid-forming proteins, we searched for all homologs of the HET-s protein in a database of protein domains and fungal genomes, using a combined application of HMM, psi blast and pGenThreader techniques, and performed a comparative evolutionary analysis of the N-terminal alpha-helical domain and the C-terminal prion-forming domain of HET-s. By assessing the tandem evolution of both domains, we observed that the prion-forming domain is restricted to Sordariomycetes, with a marginal additional sequence homolog in Arthroderma otae as a likely case of horizontal transfer. This suggests innovation and rapid evolution of the solenoid fold in the Sordariomycetes clade. In contrast, the N-terminal domain evolves at a slower rate (in Sordariomycetes) and spans many diverse clades of fungi. We performed a full three-dimensional protein threading analysis on all identified HET-s homologs against the HET-s solenoid fold, and present detailed structural annotations for identified structural homologs to the prion-forming domain. An analysis of the physicochemical characteristics in our set of structural models indicates that the HET-s solenoid shape can be readily adopted in these homologs, but that they are all less optimized for fibril formation than the P. anserina HET-s sequence itself, due chiefly to the presence of fewer asparagine ladders and salt bridges. Our combined structural and evolutionary analysis suggests that the HET-s shape has "limited scope" for amyloidosis across the wider protein universe, compared to the 'generic' left-handed beta helix. We discuss the implications of our findings on future identification of amyloid-forming proteins sharing the solenoid fold. PMID- 22096555 TI - Avian conservation practices strengthen ecosystem services in California vineyards. AB - Insectivorous Western Bluebirds (Sialia mexicana) occupy vineyard nest boxes established by California winegrape growers who want to encourage avian conservation. Experimentally, the provision of available nest sites serves as an alternative to exclosure methods for isolating the potential ecosystem services provided by foraging birds. We compared the abundance and species richness of avian foragers and removal rates of sentinel prey in treatments with songbird nest boxes and controls without nest boxes. The average species richness of avian insectivores increased by over 50 percent compared to controls. Insectivorous bird density nearly quadrupled, primarily due to a tenfold increase in Western Bluebird abundance. In contrast, there was no significant difference in the abundance of omnivorous or granivorous bird species some of which opportunistically forage on grapes. In a sentinel prey experiment, 2.4 times more live beet armyworms (Spodoptera exigua) were removed in the nest box treatment than in the control. As an estimate of the maximum foraging services provided by insectivorous birds, we found that larval removal rates measured immediately below occupied boxes averaged 3.5 times greater than in the control. Consequently the presence of Western Bluebirds in vineyard nest boxes strengthened ecosystem services to winegrape growers, illustrating a benefit of agroecological conservation practices. Predator addition and sentinel prey experiments lack some disadvantages of predator exclusion experiments and were robust methodologies for detecting ecosystem services. PMID- 22096556 TI - Advances in ITP--therapy and quality of life--a patient survey. AB - BACKGROUND: Current guidelines recommend glucocorticoids and splenectomy as standard 1(st) and 2(nd) line treatments for chronic immune thrombocytopenia (ITP). We sought to find out how German ITP-patients are treated with respect to these guidelines. METHODS: Members of a patient support association >=18 years with a self-reported history of chronic ITP>12 months were surveyed with a web based questionnaire. RESULTS: 122 questionnaires were evaluated. 70% of patients had chronic ITP for more than 5 years and 20% an average platelet count of <=30.10(9)/L. 41% of the patients reported haematomas or petechiae more than once or twice and up to 12 times or more per year and 17% oropharyngeal and nasal bleeds. 11% had been admitted to hospital during the last 12 months. 88% had received or currently receive glucocorticoids, 27% were splenectomised. IVIG had been given to 55%, rituximab to 22%, anti-D to 12%, ciclosporin to 7%, while complementary and alternative medical treatments had been used by 36%. 50 women responded to questions concerning pregnancy. 14 (28%) had been advised not to become pregnant. 23 reported pregnancies and 10 (44%) required treatment for their ITP during pregnancy. CONCLUSION: Glucocorticoids are the most common therapy for chronic ITP but complementary and alternative treatments already come second and less than 1/3 of patients are splenectomised. This and the frequent use of complementary medicines suggests patients' dissatisfaction with conventional approaches. Many patients receive off-label therapies. There is a major need for adequate counselling and care for pregnant ITP-patients. PMID- 22096557 TI - IL-2 stimulated but not unstimulated NK cells induce selective disappearance of peripheral blood cells: concomitant results to a phase I/II study. AB - In an ongoing clinical phase I/II study, 16 pediatric patients suffering from high risk leukemia/tumors received highly purified donor natural killer (NK) cell immunotherapy (NK-DLI) at day (+3) +40 and +100 post haploidentical stem cell transplantation. However, literature about the influence of NK-DLI on recipient's immune system is scarce. Here we present concomitant results of a noninvasive in vivo monitoring approach of recipient's peripheral blood (PB) cells after transfer of either unstimulated (NK-DLI(unstim)) or IL-2 (1000 U/ml, 9-14 days) activated NK cells (NK-DLI(IL-2 stim)) along with their ex vivo secreted cytokine/chemokines. We performed phenotypical and functional characterizations of the NK-DLIs, detailed flow cytometric analyses of various PB cells and comprehensive cytokine/chemokine arrays before and after NK-DLI. Patients of both groups were comparable with regard to remission status, immune reconstitution, donor chimerism, KIR mismatching, stem cell and NK-DLI dose. Only after NK-DLI(IL 2 stim) was a rapid, almost complete loss of CD56(bright)CD16(dim/-) immune regulatory and CD56(dim)CD16(+) cytotoxic NK cells, monocytes, dendritic cells and eosinophils from PB circulation seen 10 min after infusion, while neutrophils significantly increased. The reduction of NK cells was due to both, a decrease in patients' own CD69(-) NCR(low)CD62L(+) NK cells as well as to a diminishing of the transferred cells from the NK-DLI(IL-2 stim) with the CD56(bright)CD16(+/ )CD69(+)NCR(high)CD62L(-) phenotype. All cell counts recovered within the next 24 h. Transfer of NK-DLI(IL-2 stim) translated into significantly increased levels of various cytokines/chemokines (i.e. IFN-gamma, IL-6, MIP-1beta) in patients' PB. Those remained stable for at least 1 h, presumably leading to endothelial activation, leukocyte adhesion and/or extravasation. In contrast, NK-DLI(unstim) did not cause any of the observed effects. In conclusion, we assume that the adoptive transfer of NK-DLI(IL-2 stim) under the influence of ex vivo and in vivo secreted cytokines/chemokines may promote NK cell trafficking and therefore might enhance efficacy of immunotherapy. PMID- 22096558 TI - Characterization of the response of primary cells relevant to dialysis-related amyloidosis to beta2-microglobulin monomer and fibrils. AB - The formation of insoluble amyloid fibrils is associated with an array of devastating human diseases. Dialysis-related amyloidosis (DRA) is a severe complication of hemodialysis that results in the progressive destruction of the bones and joints. Elevated concentrations of beta(2)-microglobulin (beta(2)m) in the serum of subjects on hemodialysis promote the formation of amyloid fibrils in the osteoarticular tissues, but the cellular basis for the destruction of these tissues in DRA is poorly understood. In this study we performed a systematic analysis of the interaction of monomeric and fibrillar beta(2)m with primary human cells of the types present in the synovial joints of subjects with DRA. Building upon observations that macrophages infiltrate beta(2)m amyloid deposits in vivo we demonstrate that monocytes, the precursors of macrophages, cannot degrade beta(2)m fibrils, and that both monomeric beta(2)m and fibrillar beta(2)m are cytotoxic to these cells. beta(2)m fibrils also impair the formation of bone resorbing osteoclasts from monocytes and reduce the viability of osteoblasts, the cell type that produces bone. As a consequence, we predict that beta(2)m amyloid will disrupt the remodelling of the bone, which is critical for the maintenance of this tissue. Moreover, we show that beta(2)m fibrils reduce the viability of chondrocytes, rationalizing the loss of cartilage in DRA. Together, our observations demonstrate that beta(2)m cytotoxicity has multiple cellular targets in the osteoarticular tissues and is likely to be a key factor in the bone and joint destruction characteristic of DRA. PMID- 22096560 TI - Predator-prey dynamics driven by feedback between functionally diverse trophic levels. AB - Neglecting the naturally existing functional diversity of communities and the resulting potential to respond to altered conditions may strongly reduce the realism and predictive power of ecological models. We therefore propose and study a predator-prey model that describes mutual feedback via species shifts in both predator and prey, using a dynamic trait approach. Species compositions of the two trophic levels were described by mean functional traits--prey edibility and predator food-selectivity--and functional diversities by the variances. Altered edibility triggered shifts in food-selectivity so that consumers continuously respond to the present prey composition, and vice versa. This trait-mediated feedback mechanism resulted in a complex dynamic behavior with ongoing oscillations in the mean trait values, reflecting continuous reorganization of the trophic levels. The feedback was only possible if sufficient functional diversity was present in both trophic levels. Functional diversity was internally maintained on the prey level as no niche existed in our system, which was ideal under any composition of the predator level due to the trade-offs between edibility, growth and carrying capacity. The predators were only subject to one trade-off between food-selectivity and grazing ability and in the absence of immigration, one predator type became abundant, i.e., functional diversity declined to zero. In the lack of functional diversity the system showed the same dynamics as conventional models of predator-prey interactions ignoring the potential for shifts in species composition. This way, our study identified the crucial role of trade-offs and their shape in physiological and ecological traits for preserving diversity. PMID- 22096559 TI - Molecular basis of virulence in Staphylococcus aureus mastitis. AB - BACKGROUND: S. aureus is one of the main pathogens involved in ruminant mastitis worldwide. The severity of staphylococcal infection is highly variable, ranging from subclinical to gangrenous mastitis. This work represents an in-depth characterization of S. aureus mastitis isolates to identify bacterial factors involved in severity of mastitis infection. METHODOLOGY/PRINCIPAL FINDINGS: We employed genomic, transcriptomic and proteomic approaches to comprehensively compare two clonally related S. aureus strains that reproducibly induce severe (strain O11) and milder (strain O46) mastitis in ewes. Variation in the content of mobile genetic elements, iron acquisition and metabolism, transcriptional regulation and exoprotein production was observed. In particular, O11 produced relatively high levels of exoproteins, including toxins and proteases known to be important in virulence. A characteristic we observed in other S. aureus strains isolated from clinical mastitis cases. CONCLUSIONS/SIGNIFICANCE: Our data are consistent with a dose-dependant role of some staphylococcal factors in the hypervirulence of strains isolated from severe mastitis. Mobile genetic elements, transcriptional regulators, exoproteins and iron acquisition pathways constitute good targets for further research to define the underlying mechanisms of mastitis severity. PMID- 22096561 TI - Decreased glomerular filtration rate is associated with mortality and cardiovascular events in patients with hypertension: a prospective study. AB - BACKGROUND: Few studies reported the associations between decreased glomerular filtration rate (GFR) and mortality, coronary heart disease (CHD), and stroke in hypertensive patients. We aim to assess the associations between GFR and mortality, CHD, and stroke in hypertensive patients and to evaluate whether low GFR can improve the prediction of these outcomes in addition to conventional cardiovascular risk factors. METHODS AND FINDINGS: This is an observational prospective study and 3,711 eligible hypertensive patients aged >=5 years from rural areas of China were used for the present analysis. The associations between eGFR and outcomes, followed by a median of 4.9 years, were evaluated using Cox proportional hazards models adjusting for other potential confounders. Low eGFR was independently associated with risk of all-cause mortality, cardiovascular mortality, and incident stroke [multivariable adjusted hazard ratios (95% confidence intervals) for eGFR <60 ml/min/1.73 m(2) relative to eGFR >=90 ml/min/1.73 m(2) were 1.824 (1.047-3.365), 2.371 (1.109-5.068), and 2.493 (1.193 5.212), respectively]. We found no independent association between eGFR and the risk of CHD. For 4-year all-cause and cardiovascular mortality, integrated discrimination improvement (IDI) was positive when eGFR were added to traditional risk factors (1.51%, P = 0.016, and 1.99%, P = 0.017, respectively). For stroke and CHD events, net reclassification improvements (NRI) were 5.9% (P = 0.012) and 1.8% (P = 0.083) for eGFR, respectively. CONCLUSIONS: We have established an inversely independent association between eGFR and all-cause mortality, cardiovascular mortality, and stroke in hypertensive patients in rural areas of China. Further, addition of eGFR significantly improved the prediction of 4-year mortality and stroke over and above that of conventional risk factors. We recommend that eGFR be incorporated into prognostic assessment for patients with hypertension in rural areas of China. LIMITATIONS: We did not have sufficient information on atrial fibrillation to control for the potential covariate. These associations should be further confirmed in future. PMID- 22096562 TI - The role of proline rich tyrosine kinase 2 (Pyk2) on cisplatin resistance in hepatocellular carcinoma. AB - AIMS: We previously demonstrated Proline rich tyrosine kinase 2 (Pyk2) plays important roles in regulating tumor progression, migration and invasion in hepatocellular carcinoma (HCC). In this study, we aimed to examine the role of proline rich tyrosine kinase 2 (Pyk2) on cisplatin resistance in HCC and to explore its underlying molecular mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Stable transfectants either overexpressing or suppressing Pyk2 were established in different HCC cell lines. MTT, colony formation and Annexin-V assays were employed to examine their in vitro responses to cisplatin. Xenograft ectopic and orthotopic nude mice models were generated to investigate the in vivo responses of them to cisplatin treatment. cDNA microarray was performed to identify Pyk2 induced genes which were further validated by quantitative real-time RT-PCR using clinical HCC samples. In vitro functional study demonstrated that Pyk2 overexpressing HCC transfectants exhibited relatively lower cytotoxicity, higher colony-forming ability and lower apoptosis to cisplatin compared with the control transfectants. Moreover, Pyk2 overexpressing HCC transfectants had a higher survival rate under cisplatin treatment by up-regulation of AKT phosphorylation. In vivo xenograft nude mice model demonstrated that Pyk2-overexpressing transfectants developed higher tolerance to cisplatin treatment together with less tumor necrosis and apoptosis. cDNA microarray analysis revealed that there were more than 4,000 genes differentially expressed upon overexpression of Pyk2. Several upregulated genes were found to be involved in drug resistance and invasion in cancers. Among them, the expression profiles of MDR1, GAGE1, STAT1 and MAP7 were significantly associated with the expression of Pyk2 in clinical HCC samples. CONCLUSIONS: Our results may suggest a new evidence of Pyk2 on promoting cisplatin resistance of HCC cells through preventing cell apoptosis, activation of AKT pathway and upregulation of drug resistant genes. PMID- 22096563 TI - Large-scale protein-protein interaction analysis in Arabidopsis mesophyll protoplasts by split firefly luciferase complementation. AB - Protein-protein interactions (PPIs) constitute the regulatory network that coordinates diverse cellular functions. There are growing needs in plant research for creating protein interaction maps behind complex cellular processes and at a systems biology level. However, only a few approaches have been successfully used for large-scale surveys of PPIs in plants, each having advantages and disadvantages. Here we present split firefly luciferase complementation (SFLC) as a highly sensitive and noninvasive technique for in planta PPI investigation. In this assay, the separate halves of a firefly luciferase can come into close proximity and transiently restore its catalytic activity only when their fusion partners, namely the two proteins of interest, interact with each other. This assay was conferred with quantitativeness and high throughput potential when the Arabidopsis mesophyll protoplast system and a microplate luminometer were employed for protein expression and luciferase measurement, respectively. Using the SFLC assay, we could monitor the dynamics of rapamycin-induced and ascomycin disrupted interaction between Arabidopsis FRB and human FKBP proteins in a near real-time manner. As a proof of concept for large-scale PPI survey, we further applied the SFLC assay to testing 132 binary PPIs among 8 auxin response factors (ARFs) and 12 Aux/IAA proteins from Arabidopsis. Our results demonstrated that the SFLC assay is ideal for in vivo quantitative PPI analysis in plant cells and is particularly powerful for large-scale binary PPI screens. PMID- 22096564 TI - Defining the role of essential genes in human disease. AB - A greater understanding of the causes of human disease can come from identifying characteristics that are specific to disease genes. However, a full understanding of the contribution of essential genes to human disease is lacking, due to the premise that these genes tend to cause developmental abnormalities rather than adult disease. We tested the hypothesis that human orthologs of mouse essential genes are associated with a variety of human diseases, rather than only those related to miscarriage and birth defects. We segregated human disease genes according to whether the knockout phenotype of their mouse ortholog was lethal or viable, defining those with orthologs producing lethal knockouts as essential disease genes. We show that the human orthologs of mouse essential genes are associated with a wide spectrum of diseases affecting diverse physiological systems. Notably, human disease genes with essential mouse orthologs are over represented among disease genes associated with cancer, suggesting links between adult cellular abnormalities and developmental functions. The proteins encoded by essential genes are highly connected in protein-protein interaction networks, which we find correlates with an over-representation of nuclear proteins amongst essential disease genes. Disease genes associated with essential orthologs also are more likely than those with non-essential orthologs to contribute to disease through an autosomal dominant inheritance pattern, suggesting that these diseases may actually result from semi-dominant mutant alleles. Overall, we have described attributes found in disease genes according to the essentiality status of their mouse orthologs. These findings demonstrate that disease genes do occupy highly connected positions in protein-protein interaction networks, and that due to the complexity of disease-associated alleles, essential genes cannot be ignored as candidates for causing diverse human diseases. PMID- 22096565 TI - IRF8 governs expression of genes involved in innate and adaptive immunity in human and mouse germinal center B cells. AB - IRF8 (Interferon Regulatory Factor 8) is a transcription factor expressed throughout B cell differentiation except for mature plasma cells. Previous studies showed it is part of the transcriptional network governing B cell specification and commitment in the bone marrow, regulates the distribution of mature B cells into the splenic follicular and marginal zone compartments, and is expressed at highest levels in germinal center (GC) B cells. Here, we investigated the transcriptional programs and signaling pathways affected by IRF8 in human and mouse GC B cells as defined by ChIP-chip analyses and transcriptional profiling. We show that IRF8 binds a large number of genes by targeting two distinct motifs, half of which are also targeted by PU.1. Over 70% of the binding sites localized to proximal and distal promoter regions with ~25% being intragenic. There was significant enrichment among targeted genes for those involved in innate and adaptive immunity with over 30% previously defined as interferon stimulated genes. We also showed that IRF8 target genes contributes to multiple aspects of the biology of mature B cells including critical components of the molecular crosstalk among GC B cells, T follicular helper cells, and follicular dendritic cells. PMID- 22096566 TI - Distribution and characterization of progenitor cells within the human filum terminale. AB - BACKGROUND: Filum terminale (FT) is a structure that is intimately associated with conus medullaris, the most caudal part of the spinal cord. It is well documented that certain regions of the adult human central nervous system contains undifferentiated, progenitor cells or multipotent precursors. The primary objective of this study was to describe the distribution and progenitor features of this cell population in humans, and to confirm their ability to differentiate within the neuroectodermal lineage. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that neural stem/progenitor cells are present in FT obtained from patients treated for tethered cord. When human or rat FT-derived cells were cultured in defined medium, they proliferated and formed neurospheres in 13 out of 21 individuals. Cells expressing Sox2 and Musashi-1 were found to outline the central canal, and also to be distributed in islets throughout the whole FT. Following plating, the cells developed antigen profiles characteristic of astrocytes (GFAP) and neurons (beta-III-tubulin). Addition of PDGF-BB directed the cells towards a neuronal fate. Moreover, the cells obtained from young donors shows higher capacity for proliferation and are easier to expand than cells derived from older donors. CONCLUSION/SIGNIFICANCE: The identification of bona fide neural progenitor cells in FT suggests a possible role for progenitor cells in this extension of conus medullaris and may provide an additional source of such cells for possible therapeutic purposes. Filum terminale, human, progenitor cells, neuron, astrocytes, spinal cord. PMID- 22096567 TI - Mutagen-specific mutation signature determines global microRNA binding. AB - Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene products at the post-transcriptional level. It is thought that loss of cell regulation by miRNAs supports cancer development. Based on whole genome sequencing of a melanoma tumor, we predict, using three different computational algorithms, that the melanoma somatic mutations globally reduce binding of miRNAs to the mutated 3'UTRs. This phenomenon reflects the nature of the characteristic UV-induced mutation, C-to-T. Furthermore, we show that seed regions are enriched with Guanine, thus rendering miRNAs prone to reduced binding to UV-mutated 3'UTRs. Accordingly, mutation patterns in non UV-induced malignancies e.g. lung cancer and leukemia do not yield similar predictions. It is suggested that UV-induced disruption of miRNA-mediated gene regulation plays a carcinogenic role. Remarkably, dark-skinned populations have significantly higher GC content in 3'UTR SNPs than light-skinned populations, which implies on evolutionary pressure to preserve regulation by trans-acting oligonucleotides under conditions with excess UV radiation. PMID- 22096568 TI - Construction and characterization of single-chain variable fragment antibody library derived from germline rearranged immunoglobulin variable genes. AB - Antibody repertoires for library construction are conventionally harvested from mRNAs of immune cells. To examine whether germline rearranged immunoglobulin (Ig) variable region genes could be used as source of antibody repertoire, an immunized phage-displayed scFv library was prepared using splenocytic genomic DNA as template. In addition, a novel frame-shifting PCR (fsPCR) step was introduced to rescue stop codon and to enhance diversity of the complementarity-determining region 3 (CDR3). The germline scFv library was initially characterized against the hapten antigen phenyloxazolone (phOx). Sequence analysis of the phOx selective scFvs indicated that the CDRs consisted of novel as well as conserved motifs. In order to illustrate that the diversity of CDR3 was increased by the fsPCR step, a second scFv library was constructed using a single scFv clone L3G7C as a template. Despite showing similar binding characteristics towards phOx, the scFv clones that were obtained from the L3G7C-derived antibody library gave a lower non-specific binding than that of the parental L3G7C clone. To determine whether germline library represented the endogenous immune status, specific scFv clones for nucleocapsid (N) protein of SARS-associated coronavirus (SCoV) were obtained both from naive and immunized germline scFv libraries. Both libraries yielded specific anti-N scFvs that exhibited similar binding characteristics towards recombinant N protein, except the immunized library gave a larger number of specific anti-N scFv, and clones with identical nucleotide sequences were found. In conclusion, highly diversified antibody library can be efficiently constructed using germline rearranged immunoglobulin variable genes as source of antibody repertoires and fsPCR to diversify the CDR3. PMID- 22096569 TI - Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease. AB - DNA damage accumulates in genome DNA during the long life of neurons, thus DNA damage repair is indispensable to keep normal functions of neurons. We previously reported that Ku70, a critical molecule for DNA double strand break (DSB) repair, is involved in the pathology of Huntington's disease (HD). Mutant huntingtin (Htt) impaired Ku70 function via direct interaction, and Ku70 supplementation recovered phenotypes of a mouse HD model. In this study, we generate multiple Drosophila HD models that express mutant huntingtin (Htt) in eye or motor neuron by different drivers and show various phenotypes. In such fly models, Ku70 co expression recovers lifespan, locomotive activity and eye degeneration. In contrast, Ku70 reduction by heterozygous null mutation or siRNA-mediated knock down accelerates lifespan shortening and locomotion disability. These results collectively support that Ku70 is a critical mediator of the HD pathology and a candidate therapeutic target in HD. PMID- 22096570 TI - Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma. AB - Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development. PMID- 22096571 TI - DNA replication timing is maintained genome-wide in primary human myoblasts independent of D4Z4 contraction in FSH muscular dystrophy. AB - Facioscapulohumeral muscular dystrophy (FSHD) is linked to contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35.2 from 11-100 copies to 1-10 copies. The extent to which D4Z4 contraction at 4q35.2 affects overall 4q35.2 chromatin organization remains unclear. Because DNA replication timing is highly predictive of long-range chromatin interactions, we generated genome-wide replication-timing profiles for FSHD and control myogenic precursor cells. We compared non-immortalized myoblasts from four FSHD patients and three control individuals to each other and to a variety of other human cell types. This study also represents the first genome-wide comparison of replication timing profiles in non-immortalized human cell cultures. Myoblasts from both control and FSHD individuals all shared a myoblast-specific replication profile. In contrast, male and female individuals were readily distinguished by monoallelic differences in replication timing at DXZ4 and other regions across the X chromosome affected by X inactivation. We conclude that replication timing is a robust cell-type specific feature that is unaffected by FSHD-related D4Z4 contraction. PMID- 22096572 TI - Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways. AB - BACKGROUND: Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities. METHODOLOGY/PRINCIPAL FINDING: FE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (DeltaPsim) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of DeltaPsim and phosphorylation of JNK, p38, and ERK1/2 kinases. CONCLUSIONS/SIGNIFICANCE: These data suggest that FE activates a caspase independent apoptotic pathway in MCF-7 cancer cells through activation of ROS mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent. PMID- 22096573 TI - Semaphorin 3A contributes to distal pulmonary epithelial cell differentiation and lung morphogenesis. AB - RATIONALE: Semaphorin 3A (Sema3A) is a neural guidance cue that also mediates cell migration, proliferation and apoptosis, and inhibits branching morphogenesis. Because we have shown that genetic deletion of neuropilin-1, which encodes an obligatory Sema3A co-receptor, influences airspace remodeling in the smoke-exposed adult lung, we sought to determine whether genetic deletion of Sema3A altered distal lung structure. METHODS: To determine whether loss of Sema3A signaling influenced distal lung morphology, we compared pulmonary histology, distal epithelial cell morphology and maturation, and the balance between lung cell proliferation and death, in lungs from mice with a targeted genetic deletion of Sema3A (Sema3A(-/-)) and wild-type (Sema3A(+/+)) littermate controls. RESULTS: Genetic deletion of Sema3A resulted in significant perinatal lethality. At E17.5, lungs from Sema3A(-/-) mice had thickened septae and reduced airspace size. Distal lung epithelial cells had increased intracellular glycogen pools and small multivesicular and lamellar bodies with atypical ultrastructure, as well as reduced expression of type I alveolar epithelial cell markers. Alveolarization was markedly attenuated in lungs from the rare Sema3A(-/-) mice that survived the immediate perinatal period. Furthermore, Sema3A deletion was linked with enhanced postnatal alveolar septal cell death. CONCLUSIONS: These data suggest that Sema3A modulates distal pulmonary epithelial cell development and alveolar septation. Defining how Sema3A influences structural plasticity of the developing lung is a critical first step for determining if this pathway can be exploited to develop innovative strategies for repair after acute or chronic lung injury. PMID- 22096574 TI - The colony-stimulating factor-1 (CSF-1) receptor sustains ERK1/2 activation and proliferation in breast cancer cell lines. AB - Breast cancer is the second leading cause of cancer-related deaths in western countries. Colony-Stimulating Factor-1 (CSF-1) and its receptor (CSF-1R) regulate macrophage and osteoclast production, trophoblast implantation and mammary gland development. The expression of CSF-1R and/or CSF-1 strongly correlates with poor prognosis in several human epithelial tumors, including breast carcinomas. We demonstrate that CSF-1 and CSF-1R are expressed, although at different levels, in 16/17 breast cancer cell lines tested with no differences among molecular subtypes. The role of CSF-1/CSF-1R in the proliferation of breast cancer cells was then studied in MDAMB468 and SKBR3 cells belonging to different subtypes. CSF 1 administration induced ERK1/2 phosphorylation and enhanced cell proliferation in both cell lines. Furthermore, the inhibition of CSF-1/CSF-1R signaling, by CSF 1R siRNA or imatinib treatment, impaired CSF-1 induced ERK1/2 activation and cell proliferation. We also demonstrate that c-Jun, cyclin D1 and c-Myc, known for their involvement in cell proliferation, are downstream CSF-1R in breast cancer cells. The presence of a proliferative CSF-1/CSF-1R autocrine loop involving ERK1/2 was also found. The wide expression of the CSF-1/CSF-1R pair across breast cancer cell subtypes supports CSF-1/CSF-1R targeting in breast cancer therapy. PMID- 22096575 TI - SERCA2 regulates non-CF and CF airway epithelial cell response to ozone. AB - Calcium mobilization can regulate a wide range of essential functions of respiratory epithelium, including ion transport, ciliary beat frequency, and secretion of mucus, all of which are modified in cystic fibrosis (CF). SERCA2, an important controller of calcium signaling, is deficient in CF epithelium. We conducted this study to determine whether SERCA2 deficiency can modulate airway epithelial responses to environmental oxidants such as ozone. This could contribute to the pathogenesis of pulmonary exacerbations, which are important and frequent clinical events in CF. To address this, we used air-liquid interface (ALI) cultures of non-CF and CF cell lines, as well as differentiated cultures of cells derived from non-CF and CF patients. We found that ozone exposure caused enhanced membrane damage, mitochondrial dysfunction and apoptotic cell death in CF airway epithelial cell lines relative to non-CF. Ozone exposure caused increased proinflammatory cytokine production in CF airway epithelial cell lines. Elevated proinflammatory cytokine production also was observed in shRNA-mediated SERCA2 knockdown cells. Overexpression of SERCA2 reversed ozone-induced proinflammatory cytokine production. Ozone-induced proinflammatory cytokine production was NF-kappaB- dependent. In a stable NF-kappaB reporter cell line, SERCA2 inhibition and knockdown both upregulated cytomix-induced NF-kappaB activity, indicating importance of SERCA2 in modulating NF-kappaB activity. In this system, increased NF-kappaB activity was also accompanied by increased IL-8 production. Ozone also induced NF-kappaB activity and IL-8 release, an effect that was greater in SERCA2-silenced NF-kappaB-reporter cells. SERCA2 overexpression reversed cytomix-induced increased IL-8 release and total nuclear p65 in CFTR-deficient (16HBE-AS) cells. These studies suggest that SERCA2 is an important regulator of the proinflammatory response of airway epithelial cells and could be a potential therapeutic target. PMID- 22096576 TI - Estrogen receptor alpha expression in podocytes mediates protection against apoptosis in-vitro and in-vivo. AB - CONTEXT/OBJECTIVE: Epidemiological studies have demonstrated that women have a significantly better prognosis in chronic renal diseases compared to men. This suggests critical influences of gender hormones on glomerular structure and function. We examined potential direct protective effects of estradiol on podocytes. METHODS: Expression of estrogen receptor alpha (ERalpha) was examined in podocytes in vitro and in vivo. Receptor localization was shown using Western blot of separated nuclear and cytoplasmatic protein fractions. Podocytes were treated with Puromycin aminonucleoside (PAN, apoptosis induction), estradiol, or both in combination. Apoptotic cells were detected with Hoechst nuclear staining and Annexin-FITC flow cytometry. To visualize mitochondrial membrane potential depolarization as an indicator for apoptosis, cells were stained with tetramethyl rhodamine methylester (TMRM). Estradiol-induced phosphorylation of ERK1/2 and p38 MAPK was examined by Western blot. Glomeruli of ERalpha knock-out mice and wild type controls were analysed by histomorphometry and immunohistochemistry. RESULTS: ERalpha was consistently expressed in human and murine podocytes. Estradiol stimulated ERalpha protein expression, reduced PAN-induced apoptosis in vitro by 26.5+/-24.6% or 56.6+/-5.9% (flow cytometry or Hoechst-staining, respectively; both p<0.05), and restored PAN-induced mitochondrial membrane potential depolarization. Estradiol enhanced ERK1/2 phosphorylation. In ERalpha knockout mice, podocyte number was reduced compared to controls (female/male: 80/86 vs. 132/135 podocytes per glomerulus, p<0.05). Podocyte volume was enhanced in ERalpha knockout mice (female/male: 429/371 um(3) vs. 264/223 um(3) in controls, p<0.05). Tgfbeta1 and collagen type IV expression were increased in knockout mice, indicating glomerular damage. CONCLUSIONS: Podocytes express ERalpha, whose activation leads to a significant protection against experimentally induced apoptosis. Possible underlying mechanisms include stabilization of mitochondrial membrane potential and activation of MAPK signalling. Characteristic morphological changes indicating glomerulopathy in ERalpha knock-out mice support the in vivo relevance of the ERalpha for podocyte viability and function. Thus, our findings provide a novel model for the protective influence of female gender on chronic glomerular diseases. PMID- 22096578 TI - Fish geometry and electric organ discharge determine functional organization of the electrosensory epithelium. AB - Active electroreception in Gymnotus omarorum is a sensory modality that perceives the changes that nearby objects cause in a self generated electric field. The field is emitted as repetitive stereotyped pulses that stimulate skin electroreceptors. Differently from mormyriformes electric fish, gymnotiformes have an electric organ distributed along a large portion of the body, which fires sequentially. As a consequence shape and amplitude of both, the electric field generated and the image of objects, change during the electric pulse. To study how G. omarorum constructs a perceptual representation, we developed a computational model that allows the determination of the self-generated field and the electric image. We verify and use the model as a tool to explore image formation in diverse experimental circumstances. We show how the electric images of objects change in shape as a function of time and position, relative to the fish's body. We propose a theoretical framework about the organization of the different perceptive tasks made by electroreception: 1) At the head region, where the electrosensory mosaic presents an electric fovea, the field polarizing nearby objects is coherent and collimated. This favors the high resolution sampling of images of small objects and perception of electric color. Besides, the high sensitivity of the fovea allows the detection and tracking of large faraway objects in rostral regions. 2) In the trunk and tail region a multiplicity of sources illuminate different regions of the object, allowing the characterization of the shape and position of a large object. In this region, electroreceptors are of a unique type and capacitive detection should be based in the pattern of the afferents response. 3) Far from the fish, active electroreception is not possible but the collimated field is suitable to be used for electrocommunication and detection of large objects at the sides and caudally. PMID- 22096577 TI - Defects in the medial entorhinal cortex and dentate gyrus in the mouse model of Sanfilippo syndrome type B. AB - Sanfilippo syndrome type B (MPS IIIB) is characterized by profound mental retardation in childhood, dementia and death in late adolescence; it is caused by deficiency of alpha-N-acetylglucosaminidase and resulting lysosomal storage of heparan sulfate. A mouse model, generated by homologous recombination of the Naglu gene, was used to study pathological changes in the brain. We found earlier that neurons in the medial entorhinal cortex (MEC) and the dentate gyrus showed a number of secondary defects, including the presence of hyperphosphorylated tau (Ptau) detected with antibodies raised against Ptau in Alzheimer disease brain. By further use of immunohistochemistry, we now show staining in neurons of the same area for beta amyloid, extending the resemblance to Alzheimer disease. Ptau inclusions in the dentate gyrus of MPS IIIB mice were reduced in number when the mice were administered LiCl, a specific inhibitor of Gsk3beta. Additional proteins found elevated in MEC include proteins involved in autophagy and the heparan sulfate proteoglycans, glypicans 1 and 5, the latter closely related to the primary defect. The level of secondary accumulations was associated with elevation of glypican, as seen by comparing brains of mice at different ages or with different mucopolysaccharide storage diseases. The MEC of an MPS IIIA mouse had the same intense immunostaining for glypican 1 and other markers as MPS IIIB, while MEC of MPS I and MPS II mice had weak staining, and MEC of an MPS VI mouse had no staining at all for the same proteins. A considerable amount of glypican was found in MEC of MPS IIIB mice outside of lysosomes. We propose that it is the extralysosomal glypican that would be harmful to neurons, because its heparan sulfate branches could potentiate the formation of Ptau and beta amyloid aggregates, which would be toxic as well as difficult to degrade. PMID- 22096580 TI - Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation. AB - Infants with severe primary combined immunodeficiency (SCID) and children post allogeneic hematopoietic stem cell transplantation (HSCT) are extremely susceptible to unusual infections. The lack of generic tools to detect disease causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA) techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients. PMID- 22096579 TI - A role for the ubiquitin ligase Nedd4 in membrane sorting of LAPTM4 proteins. AB - BACKGROUND: The lysosome associated protein transmembrane (LAPTM) family is comprised of three members: LAPTM5, LAPTM4a and LAPTM4b, with the latter previously shown to be overexpressed in numerous cancers. While we had demonstrated earlier the requirement of the E3 ubiquitin ligase Nedd4 for LAPTM5 sorting to lysosomes, the regulation of sorting of LAPTM4 proteins is less clear. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that LAPTM4a and LAPTM4b are localized to the lysosome, but unique to LAPTM4b, a fraction of it is present at the plasma membrane and its overexpression induces the formation of actin-based membrane protrusions. We demonstrate that LAPTM4s, like LAPTM5, are able to co immunoprecipitate with the E3 ubiquitin ligase Nedd4, an interaction that is dependent on LAPTM4 PY motifs and plays a role in membrane sorting. Accordingly, in Nedd4 knockout mouse embryonic fibroblasts (MEFs), LAPTM4a and LAPTM4b show reduced lysosomal localization. Moreover, lack of PY motifs leads to enhanced missorting of LAPTM4b to the plasma membrane instead of the lysosome. CONCLUSIONS/SIGNIFICANCE: These results suggest that while some requisites of LAPTM5 lysosomal sorting are conserved among LAPTM4 proteins, LAPTM4a and LAPTM4b have also developed distinct sorting requirements. PMID- 22096581 TI - Metabolic patterns and biotransformation activities of resveratrol in human glioblastoma cells: relevance with therapeutic efficacies. AB - BACKGROUND: Trans-resveratrol rather than its biotransformed monosulfate metabolite exerts anti-medulloblastoma effects by suppressing STAT3 activation. Nevertheless, its effects on human glioblastoma cells are variable due to certain unknown reason(s). METHODOLOGY/PRINCIPAL FINDINGS: Citing resveratrol-sensitive UW228-3 medulloblastoma cell line and primarily cultured rat brain cells/PBCs as controls, the effect of resveratrol on LN-18 human glioblastoma cells and its relevance with metabolic pattern(s), brain-associated sulfotransferase/SULT expression and the statuses of STAT3 signaling and protein inhibitor of activated STAT3 (PIAS3) were elucidated by multiple experimental approaches. Meanwhile, the expression patterns of three SULTs (SULT1A1, 1C2 and 4A1) in human glioblastoma tumors were profiled immunohistochemically. The results revealed that 100 uM resveratrol-treated LN-18 generated the same metabolites as UW228-3 cells, while additional metabolite in molecular weight of 403.0992 in negative ion mode was found in PBCs. Neither growth arrest nor apoptosis was found in resveratrol treated LN-18 and PBC cells. Upon resveratrol treatment, the levels of SULT1A1, 1C2 and 4A1 expression in LN-18 cells were more up-regulated than that expressed in UW228-3 cells and close to the levels in PBCs. Immunohistochemical staining showed that 42.0%, 27.1% and 19.6% of 149 glioblastoma cases produced similar SULT1A1, 1C2 and 4A1 levels as that of tumor-surrounding tissues. Unlike the situation in UW228-3 cells, STAT3 signaling remained activated and its protein inhibitor PIAS3 was restricted in the cytosol of resveratrol-treated LN-18 cells. No nuclear translocation of STAT3 and PIAS3 was observed in resveratrol-treated PBCs. Treatment with STAT3 chemical inhibitor, AG490, committed majority of LN-18 and UW228-3 cells but not PBCs to apoptosis within 48 hours. CONCLUSIONS/SIGNIFICANCE: LN-18 glioblastoma cells are insensitive to resveratrol due to the more inducible brain-associated SULT expression, insufficiency of resveratrol to suppress activated STAT3 signaling and the lack of PIAS3 nuclear translocation. The findings from PBCs suggest that an effective anticancer dose of resveratrol exerts little side effect on normal brain cells. PMID- 22096582 TI - Quantifying killing of orangutans and human-orangutan conflict in Kalimantan, Indonesia. AB - Human-orangutan conflict and hunting are thought to pose a serious threat to orangutan existence in Kalimantan, the Indonesian part of Borneo. No data existed prior to the present study to substantiate these threats. We investigated the rates, spatial distribution and causes of conflict and hunting through an interview-based survey in the orangutan's range in Kalimantan, Indonesia. Between April 2008 and September 2009, we interviewed 6983 respondents in 687 villages to obtain socio-economic information, assess knowledge of local wildlife in general and orangutan encounters specifically, and to query respondents about their knowledge on orangutan conflicts and killing, and relevant laws. This survey revealed estimated killing rates of between 750 and 1800 animals killed in the last year, and between 1950 and 3100 animals killed per year on average within the lifetime of the survey respondents. These killing rates are higher than previously thought and are high enough to pose a serious threat to the continued existence of orangutans in Kalimantan. Importantly, the study contributes to our understanding of the spatial variation in threats, and the underlying causes of those threats, which can be used to facilitate the development of targeted conservation management. PMID- 22096583 TI - Arctic Ocean microbial community structure before and after the 2007 record sea ice minimum. AB - Increasing global temperatures are having a profound impact in the Arctic, including the dramatic loss of multiyear sea ice in 2007 that has continued to the present. The majority of life in the Arctic is microbial and the consequences of climate-mediated changes on microbial marine food webs, which are responsible for biogeochemical cycling and support higher trophic levels, are unknown. We examined microbial communities over time by using high-throughput sequencing of microbial DNA collected between 2003 and 2010 from the subsurface chlorophyll maximum (SCM) layer of the Beaufort Sea (Canadian Arctic). We found that overall this layer has freshened and concentrations of nitrate, the limiting nutrient for photosynthetic production in Arctic seas, have decreased. We compared microbial communities from before and after the record September 2007 sea ice minimum and detected significant differences in communities from all three domains of life. In particular, there were significant changes in species composition of Eukarya, with ciliates becoming more common and heterotrophic marine stramenopiles (MASTs) accounting for a smaller proportion of sequences retrieved after 2007. Within the Archaea, Marine Group I Thaumarchaeota, which earlier represented up to 60% of the Archaea sequences in this layer, have declined to <10%. Bacterial communities overall were less diverse after 2007, with a significant decrease of the Bacteroidetes. These significant shifts suggest that the microbial food webs are sensitive to physical oceanographic changes such as those occurring in the Canadian Arctic over the past decade. PMID- 22096584 TI - Mild functional differences of dynamin 2 mutations associated to centronuclear myopathy and Charcot-Marie Tooth peripheral neuropathy. AB - The large GTPase dynamin 2 is a key player in membrane and cytoskeletal dynamics mutated in centronuclear myopathy (CNM) and Charcot-Marie Tooth (CMT) neuropathy, two discrete dominant neuromuscular disorders affecting skeletal muscle and peripheral nerves respectively. The molecular basis for the tissue-specific phenotypes observed and the physiopathological mechanisms linked to dynamin 2 mutations are not well established. In this study, we have analyzed the impact of CNM and CMT implicated dynamin 2 mutants using ectopic expression of four CNM and two CMT mutations, and patient fibroblasts harboring two dynamin 2 CNM mutations in established cellular processes of dynamin 2 action. Wild type and CMT mutants were seen in association with microtubules whereas CNM mutants lacked microtubules association and did not disrupt interphase microtubules dynamics. Most dynamin 2 mutants partially decreased clathrin-mediated endocytosis when ectopically expressed in cultured cells; however, experiments in patient fibroblasts suggested that endocytosis is overall not defective. Furthermore, CNM mutants were seen in association with enlarged clathrin stained structures whereas the CMT mutant constructs were associated with clathrin structures that appeared clustered, similar to the structures observed in Dnm1 and Dnm2 double knock-out cells. Other roles of dynamin 2 including its interaction with BIN1 (amphiphysin 2), and its function in Golgi maintenance and centrosome cohesion were not significantly altered. Taken together, these mild functional defects are suggestive of differences between CMT and CNM disease-causing dynamin 2 mutants and suggest that a slight impairment in clathrin-mediated pathways may accumulate over time to foster the respective human diseases. PMID- 22096585 TI - Up-regulation of A1M/alpha1-microglobulin in skin by heme and reactive oxygen species gives protection from oxidative damage. AB - During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin alpha(1) microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96*10(-6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding. PMID- 22096586 TI - Comparing the MRI appearance of the lymph nodes and spleen in wild-type and immuno-deficient mouse strains. AB - The goal of this study was to investigate the normal MRI appearance of lymphoid organs in immuno-competent and immuno-deficient mice commonly used in research. Four mice from each of four different mouse strains (nude, NOG, C57BL/6, CB-17 SCID (SCID)) were imaged weekly for one month. Images were acquired with a 3D balanced steady state free precession (bSSFP) sequence. The volume of the lymph nodes and spleens were measured from MR images. In images of nude and SCID mice, lymph nodes sometimes contained a hyperintense region visible on MRI images. Volumes of the nodes were highly variable in nude mice. Nodes in SCID mice were smaller than in nude or C57Bl/6 mice (p<0.0001). Lymph node volumes changed slightly over time in all strains. The spleens of C57Bl/6 and nude mice were similar in size and appearance. Spleens of SCID and NOG mice were significantly smaller (p<0.0001) and abnormal in appearance. The MRI appearance of the normal lymph nodes and spleen varies considerably in the various mouse strains examined in this study. This is important to recognize in order to avoid the misinterpretation of MRI findings as abnormal when these strains are used in MRI imaging studies. PMID- 22096587 TI - Atypical scrapie isolates involve a uniform prion species with a complex molecular signature. AB - The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrP(d)). To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338). The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research. PMID- 22096588 TI - Infections in infants during the first 12 months of life: role of placental malaria and environmental factors. AB - BACKGROUND: The association between placental malaria (PM) and first peripheral parasitaemias in early infancy was assessed in Tori Bossito, a rural area of Benin with a careful attention on transmission factors at an individual level. METHODOLOGY: Statistical analysis was performed on 550 infants followed weekly from birth to 12 months. Malaria transmission was assessed by anopheles human landing catches every 6 weeks in 36 sampling houses and season defined by rainfall. Each child was located by GPS and assigned to the closest anopheles sampling house. Data were analysed by survival Cox models, stratified on the possession of insecticide-treated mosquito nets (ITNs) at enrolment. PRINCIPAL FINDINGS: Among infants sleeping in a house with an ITN, PM was found to be highly associated to first malaria infections, after adjusting on season, number of anopheles, antenatal care (ANC) visits and maternal severe anaemia. Infants born from a malaria infected placenta had a 2.13 fold increased risk to present a first malaria infection than those born from a non infected placenta ([1.24 3.67], p<0.01) when sleeping in a house with an ITN. The risk to present a first malaria infection was increased by 3.2 to 6.5, according to the level of anopheles exposure (moderate or high levels, compared to the absence of anopheles). CONCLUSIONS: First malaria infections in early childhood can be attributed simultaneously to both PM and high levels of exposure to infected anopheles. Protective measures as Intermittent Preventive Treatment during pregnancy (IPTp) and ITNs, targeted on both mothers and infants should be reinforced, as well as the research on new drugs and insecticides. In parallel, investigations on placental malaria have to be strengthened to better understand the mechanisms involved, and thus to protect adequately the infants high risk group. PMID- 22096590 TI - Amoeboid cells use protrusions for walking, gliding and swimming. AB - Amoeboid cells crawl using pseudopods, which are convex extensions of the cell surface. In many laboratory experiments, cells move on a smooth substrate, but in the wild cells may experience obstacles of other cells or dead material, or may even move in liquid. To understand how cells cope with heterogeneous environments we have investigated the pseudopod life cycle of wild type and mutant cells moving on a substrate and when suspended in liquid. We show that the same pseudopod cycle can provide three types of movement that we address as walking, gliding and swimming. In walking, the extending pseudopod will adhere firmly to the substrate, which allows cells to generate forces to bypass obstacles. Mutant cells with compromised adhesion can move much faster than wild type cells on a smooth substrate (gliding), but cannot move effectively against obstacles that provide resistance. In a liquid, when swimming, the extending pseudopods convert to side-bumps that move rapidly to the rear of the cells. Calculations suggest that these bumps provide sufficient drag force to mediate the observed forward swimming of the cell. PMID- 22096589 TI - Yes-associated protein expression in head and neck squamous cell carcinoma nodal metastasis. AB - INTRODUCTION: Yes-associated protein (YAP) is considered an oncogene found amplified in multiple tumors, including head and neck squamous cell carcinoma (HNSCC). However, the role for YAP expression in HNSCC is not understood. Based on the central role of YAP in the hippo pathway, we tested if YAP was associated with the stage of HNSCC progression and metastatic potential. METHODS: To determine the expression of YAP in human benign and HNSCC tissue specimens, immunohistochemical analyses were performed in whole tissue samples and tissue microarrays. The expression of YAP in tissues of microarray was first associated with clinic-pathologic factors and results verified in samples from whole tissue sections. To investigate the role of YAP and p63 in regulating HNSCC epithelial to mesenchymal transition, epithelial and mesenchymal markers were assayed in Fadu and SCC-25 cells, HNSCC cells with endogenously elevated YAP expression and siRNA-mediated expression knockdown. RESULTS: Analysis of human HNSCC tissues suggested YAP expression was elevated in tumors compared to benign tissues and specifically localized at the tumor invasive front (p value < 0.05). But, indexed YAP expression was lower with greater tumor grade (p value = 0.02). In contrast, p63 expression was primarily elevated in high-grade tumors. Interestingly, both YAP and p63 was strongly expressed at the tumor invasive front and in metastatic HNSCC. Strikingly, we demonstrated YAP expression in the primary HNSCC tumor was associated with nodal metastasis in univariate analysis (p value = 0.02). However, the knockdown of YAP in Fadu and SCC-25 cell lines was not associated with changes in epithelial to mesenchymal transdifferentiation or p63 expression. CONCLUSION: Together, YAP expression, in combination with p63 can facilitate identification of HNSCC tumors from hyperplastic and benign tissues and the metastatic function of YAP in HNSCC may not be a result of epithelia to mesenchymal transdifferentiation. PMID- 22096591 TI - A graphical user interface for a method to infer kinetics and network architecture (MIKANA). AB - One of the main challenges in the biomedical sciences is the determination of reaction mechanisms that constitute a biochemical pathway. During the last decades, advances have been made in building complex diagrams showing the static interactions of proteins. The challenge for systems biologists is to build realistic models of the dynamical behavior of reactants, intermediates and products. For this purpose, several methods have been recently proposed to deduce the reaction mechanisms or to estimate the kinetic parameters of the elementary reactions that constitute the pathway. One such method is MIKANA: Method to Infer Kinetics And Network Architecture. MIKANA is a computational method to infer both reaction mechanisms and estimate the kinetic parameters of biochemical pathways from time course data. To make it available to the scientific community, we developed a Graphical User Interface (GUI) for MIKANA. Among other features, the GUI validates and processes an input time course data, displays the inferred reactions, generates the differential equations for the chemical species in the pathway and plots the prediction curves on top of the input time course data. We also added a new feature to MIKANA that allows the user to exclude a priori known reactions from the inferred mechanism. This addition improves the performance of the method. In this article, we illustrate the GUI for MIKANA with three examples: an irreversible Michaelis-Menten reaction mechanism; the interaction map of chemical species of the muscle glycolytic pathway; and the glycolytic pathway of Lactococcus lactis. We also describe the code and methods in sufficient detail to allow researchers to further develop the code or reproduce the experiments described. The code for MIKANA is open source, free for academic and non-academic use and is available for download (Information S1). PMID- 22096592 TI - Prenatal stress induces long-term effects in cell turnover in the hippocampus hypothalamus-pituitary axis in adult male rats. AB - Subchronic gestational stress leads to permanent modifications in the hippocampus hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID- 22096593 TI - Gene expression profile change and associated physiological and pathological effects in mouse liver induced by fasting and refeeding. AB - Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes. PMID- 22096595 TI - Potential accumulative effect of the herbicide glyphosate on glyphosate-tolerant maize rhizobacterial communities over a three-year cultivation period. AB - BACKGROUND: Glyphosate is a herbicide that is liable to be used in the extensive cultivation of glyphosate-tolerant cultivars. The potential accumulation of the relative effect of glyphosate on the rhizobacterial communities of glyphosate tolerant maize has been monitored over a period of three years. METHODOLOGY/PRINCIPAL FINDINGS: The composition of rhizobacterial communities is known to vary with soil texture, hence, the analyses have been performed in two agricultural fields with a different soil texture. The accumulative effects of glyphosate have been monitored by means of high throughput DNA pyrosequencing of the bacterial DNA coding for the 16S rRNA hypervariable V6 region from rhizobacterial communities. The relative composition of the rhizobacterial communities does vary in each field over the three-year period. The overall distribution of the bacterial phyla seems to change from one year to the next similarly in the untreated and glyphosate-treated soils in both fields. The two methods used to estimate bacterial diversity offered consistent results and are equally suitable for diversity assessment. CONCLUSIONS/SIGNIFICANCE: The glyphosate treatment during the three-year period of seasonal cultivation in two different fields did not seem to significantly change the maize rhizobacterial communities when compared to those of the untreated soil. This may be particularly relevant with respect to a potential authorisation to cultivate glyphosate-tolerant maize in the European Union. PMID- 22096594 TI - Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants. AB - Multielectrodes have been used with great success to simultaneously record the activity of neuronal populations in awake, behaving animals. In particular, there is great promise in the use of this technique to allow the control of neuroprosthetic devices by human patients. However, it is crucial to fully characterize the tissue response to the chronic implants in animal models ahead of the initiation of human clinical trials. Here we evaluated the effects of unilateral multielectrode implants on the motor cortex of rats weekly recorded for 1-6 months using several histological methods to assess metabolic markers, inflammatory response, immediate-early gene (IEG) expression, cytoskeletal integrity and apoptotic profiles. We also investigated the correlations between each of these features and firing rates, to estimate the impact of post-implant time on neuronal recordings. Overall, limited neuronal loss and glial activation were observed on the implanted sites. Reactivity to enzymatic metabolic markers and IEG expression were not significantly different between implanted and non implanted hemispheres. Multielectrode recordings remained viable for up to 6 months after implantation, and firing rates correlated well to the histochemical and immunohistochemical markers. Altogether, our results indicate that chronic tungsten multielectrode implants do not substantially alter the histological and functional integrity of target sites in the cerebral cortex. PMID- 22096597 TI - Average rank-based score to measure deregulation of molecular pathway gene sets. AB - BACKGROUND: Deregulation of biological pathways has been shown to be involved in the turmorigenesis of a variety of cancers. The co-regulation of pathways in tumor and normal tissues has not been studied in a systematic manner. RESULTS: In this study we propose a novel statistic named AR-score (average rank based score) to measure pathway activities based on microarray gene expression profiles. We calculate and compare the AR-scores of pathways in microarray datasets containing expression profiles for a wide range of cancer types as well as the corresponding normal tissues. We find that many pathways undergo significant activity changes in tumors with respect to normal tissues. AR-scores for a small subset of pathways are capable of distinguishing tumor from normal tissues or classifying tumor subtypes. In normal tissues many pathways are highly correlated in their activities, whereas their correlations reduce significantly in tumors and cancer cell lines. The co-expression of genes in the same pathways was also significantly perturbed in tumors. CONCLUSIONS: The co-regulation of genes in the same pathways and co-regulation of different pathways are significantly perturbed in tumors versus normal tissues. Our method provides a useful tool for better understanding the mechanistic changes in tumors, which can also be used for exploring other biological problems. PMID- 22096596 TI - RGS9 knockout causes a short delay in light responses of ON-bipolar cells. AB - RGS9 and R9AP are components of the photoreceptor-specific GTPase activating complex responsible for rapid inactivation of the G protein, transducin, in the course of photoresponse recovery from excitation. The amount of this complex in photoreceptors is strictly dependent on the expression level of R9AP; consequently, the knockouts of either RGS9 or R9AP cause comparable delays in photoresponse recovery. While RGS9 is believed to be present only in rods and cones, R9AP is also expressed in dendritic tips of ON-bipolar cells, which receive synaptic inputs from photoreceptors. Recent studies demonstrated that knockouts of R9AP and its binding partner in ON-bipolar cells, RGS11, cause a small delay in ON-bipolar cell light responses manifested as a delayed onset of electroretinography b-waves. This led the authors to suggest that R9AP and RGS11 participate in regulating the kinetics of light responses in these cells. Here we report the surprising finding that a nearly identical b-wave delay is observed in RGS9 knockout mice. Given the exclusive localization of RGS9 in photoreceptors, this result argues for a presynaptic origin of the b-wave delay in this case and perhaps in the case of the R9AP knockout as well, since R9AP is expressed in both photoreceptors and ON-bipolar cells. We also conducted a detailed analysis of the b-wave rising phase kinetics in both knockout animal types and found that, despite a delayed b-wave onset, the slope of the light response is unaffected or increased, dependent on the light stimulus intensity. This result is inconsistent with a slowdown of response propagation in ON-bipolar cells caused by the R9AP knockout, further arguing against the postsynaptic nature of the delayed b-wave phenotype in RGS9 and R9AP knockout mice. PMID- 22096598 TI - Signs of selective pressure on genetic variants affecting human height. AB - Many decades of scientific investigation have proved the role of selective pressure in Homo Sapiens at least at the level of individual genes or loci. Nevertheless, there are examples of polygenic traits that are bound to be under selection, but studies devoted to apply population genetics methods to unveil such occurrence are still lacking. Stature provides a relevant example of well studied polygenic trait for which is now available a genome-wide association study which has identified the genes involved in this trait, and which is known to be under selection. We studied the behavior of F(ST) in a simulated toy model to detect population differentiation on a generic polygenic phenotype under selection. The simulations showed that the set of alleles involved in the trait has a higher mean F(ST) value than those undergoing genetic drift only. In view of this we looked for an increase in the mean F(ST) value of the 180 variants associated to human height. For this set of alleles we found F(ST) to be significantly higher than the genomic background (p = 0.0356). On the basis of a statistical analysis we excluded that the increase was just due to the presence of outliers. We also proved as marginal the role played by local adaptation phenomena, even on different phenotypes in linkage disequilibrium with genetic variants involved in height. The increase of F(ST) for the set of alleles involved in a polygenic trait seems to provide an example of symmetry breaking phenomenon concerning the population differentiation. The splitting in the allele frequencies would be driven by the initial conditions in the population dynamics which are stochastically modified by events like drift, bottlenecks, etc, and other stochastic events like the born of new mutations. PMID- 22096599 TI - A non-verbal Turing test: differentiating mind from machine in gaze-based social interaction. AB - In social interaction, gaze behavior provides important signals that have a significant impact on our perception of others. Previous investigations, however, have relied on paradigms in which participants are passive observers of other persons' gazes and do not adjust their gaze behavior as is the case in real-life social encounters. We used an interactive eye-tracking paradigm that allows participants to interact with an anthropomorphic virtual character whose gaze behavior is responsive to where the participant looks on the stimulus screen in real time. The character's gaze reactions were systematically varied along a continuum from a maximal probability of gaze aversion to a maximal probability of gaze-following during brief interactions, thereby varying contingency and congruency of the reactions. We investigated how these variations influenced whether participants believed that the character was controlled by another person (i.e., a confederate) or a computer program. In a series of experiments, the human confederate was either introduced as naive to the task, cooperative, or competitive. Results demonstrate that the ascription of humanness increases with higher congruency of gaze reactions when participants are interacting with a naive partner. In contrast, humanness ascription is driven by the degree of contingency irrespective of congruency when the confederate was introduced as cooperative. Conversely, during interaction with a competitive confederate, judgments were neither based on congruency nor on contingency. These results offer important insights into what renders the experience of an interaction truly social: Humans appear to have a default expectation of reciprocation that can be influenced drastically by the presumed disposition of the interactor to either cooperate or compete. PMID- 22096600 TI - Cell motility dynamics: a novel segmentation algorithm to quantify multi-cellular bright field microscopy images. AB - Confocal microscopy analysis of fluorescence and morphology is becoming the standard tool in cell biology and molecular imaging. Accurate quantification algorithms are required to enhance the understanding of different biological phenomena. We present a novel approach based on image-segmentation of multi cellular regions in bright field images demonstrating enhanced quantitative analyses and better understanding of cell motility. We present MultiCellSeg, a segmentation algorithm to separate between multi-cellular and background regions for bright field images, which is based on classification of local patches within an image: a cascade of Support Vector Machines (SVMs) is applied using basic image features. Post processing includes additional classification and graph-cut segmentation to reclassify erroneous regions and refine the segmentation. This approach leads to a parameter-free and robust algorithm. Comparison to an alternative algorithm on wound healing assay images demonstrates its superiority. The proposed approach was used to evaluate common cell migration models such as wound healing and scatter assay. It was applied to quantify the acceleration effect of Hepatocyte growth factor/scatter factor (HGF/SF) on healing rate in a time lapse confocal microscopy wound healing assay and demonstrated that the healing rate is linear in both treated and untreated cells, and that HGF/SF accelerates the healing rate by approximately two-fold. A novel fully automated, accurate, zero-parameters method to classify and score scatter-assay images was developed and demonstrated that multi-cellular texture is an excellent descriptor to measure HGF/SF-induced cell scattering. We show that exploitation of textural information from differential interference contrast (DIC) images on the multi cellular level can prove beneficial for the analyses of wound healing and scatter assays. The proposed approach is generic and can be used alone or alongside traditional fluorescence single-cell processing to perform objective, accurate quantitative analyses for various biological applications. PMID- 22096601 TI - Cystathionine beta-synthase deficiency causes fat loss in mice. AB - Cystathionine beta synthase (CBS) is the rate-limiting enzyme responsible for the de novo synthesis of cysteine. Patients with CBS deficiency have greatly elevated plasma total homocysteine (tHcy), decreased levels of plasma total cysteine (tCys), and often a marfanoid appearance characterized by thinness and low body mass index (BMI). Here, we characterize the growth and body mass characteristics of CBS deficient TgI278T Cbs(-/-) mice and show that these animals have significantly decreased fat mass and tCys compared to heterozygous sibling mice. The decrease in fat mass is accompanied by a 34% decrease in liver glutathione (GSH) along with a significant decrease in liver mRNA and protein for the critical fat biosynthesizing enzyme Stearoyl CoA desaturase-1 (Scd-1). Because plasma tCys has been positively associated with fat mass in humans, we tested the hypothesis that decreased tCys in TgI278T Cbs(-/-) mice was the cause of the lean phenotype by placing the animals on water supplemented with N-acetyl cysteine (NAC) from birth to 240 days of age. Although NAC treatment in TgI278T Cbs(-/-) mice caused significant increase in serum tCys and liver GSH, there was no increase in body fat content or in liver Scd-1 levels. Our results show that lack of CBS activity causes loss of fat mass, and that this effect appears to be independent of low serum tCys. PMID- 22096602 TI - The PHD finger of human UHRF1 reveals a new subgroup of unmethylated histone H3 tail readers. AB - The human UHRF1 protein (ubiquitin-like containing PHD and RING finger domains 1) has emerged as a potential cancer target due to its implication in cell cycle regulation, maintenance of DNA methylation after replication and heterochromatin formation. UHRF1 functions as an adaptor protein that binds to histones and recruits histone modifying enzymes, like HDAC1 or G9a, which exert their action on chromatin. In this work, we show the binding specificity of the PHD finger of human UHRF1 (huUHRF1-PHD) towards unmodified histone H3 N-terminal tail using native gel electrophoresis and isothermal titration calorimetry. We report the molecular basis of this interaction by determining the crystal structure of huUHRF1-PHD in complex with the histone H3 N-terminal tail. The structure reveals a new mode of histone recognition involving an extra conserved zinc finger preceding the conventional PHD finger region. This additional zinc finger forms part of a large surface cavity that accommodates the side chain of the histone H3 lysine K4 (H3K4) regardless of its methylation state. Mutation of Q330, which specifically interacts with H3K4, to alanine has no effect on the binding, suggesting a loose interaction between huUHRF1-PHD and H3K4. On the other hand, the recognition appears to rely on histone H3R2, which fits snugly into a groove on the protein and makes tight interactions with the conserved aspartates D334 and D337. Indeed, a mutation of the former aspartate disrupts the formation of the complex, while mutating the latter decreases the binding affinity nine-fold. PMID- 22096603 TI - Antibiotics shaping bacterial genome: deletion of an IS91 flanked virulence determinant upon exposure to subinhibitory antibiotic concentrations. AB - The nucleoid-associated proteins Hha and YdgT repress the expression of the toxin alpha-hemolysin. An Escherichia coli mutant lacking these proteins overexpresses the toxin alpha-hemolysin encoded in the multicopy recombinant plasmid pANN202 312R. Unexpectedly, we could observe that this mutant generated clones that no further produced hemolysin (Hly(-)). Generation of Hly(-) clones was dependent upon the presence in the culture medium of the antibiotic kanamycin (km), a marker of the hha allele (hha::Tn5). Detailed analysis of different Hly(-) clones evidenced that recombination between partial IS91 sequences that flank the hly operon had occurred. A fluctuation test evidenced that the presence of km in the culture medium was underlying the generation of these clones. A decrease of the km concentration from 25 mg/l to 12.5 mg/l abolished the appearance of Hly(-) derivatives. We considered as a working hypothesis that, when producing high levels of the toxin (combination of the hha ydgT mutations with the presence of the multicopy hemolytic plasmid pANN202-312R), the concentration of km of 25 mg/l resulted subinhibitory and stimulated the recombination between adjacent IS91 flanking sequences. To further test this hypothesis, we analyzed the effect of subinhibitory km concentrations in the wild type E. coli strain MG1655 harboring the parental low copy number plasmid pHly152. At a km concentration of 5 mg/l, subinhibitory for strain MG1655 (pHly152), generation of Hly(-) clones could be readily detected. Similar results were also obtained when, instead of km, ampicillin was used. IS91 is flanking several virulence determinants in different enteric bacterial pathogenic strains from E. coli and Shigella. The results presented here evidence that stress generated by exposure to subinhibitory antibiotic concentrations may result in rearrangements of the bacterial genome. Whereas some of these rearrangements may be deleterious, others may generate genotypes with increased virulence, which may resume infection. PMID- 22096604 TI - New insights into the structure of (1->3,1->6)-beta-D-glucan side chains in the Candida glabrata cell wall. AB - beta-Glucan is a (1->3)-beta-linked glucose polymer with (1->6)-beta-linked side chains and a major component of fungal cell walls. beta-Glucans provide structural integrity to the fungal cell wall. The nature of the (1-6)-beta-linked side chain structure of fungal (1->3,1->6)-beta-D-glucans has been very difficult to elucidate. Herein, we report the first detailed structural characterization of the (1->6)-beta-linked side chains of Candida glabrata using high-field NMR. The (1->6)-beta-linked side chains have an average length of 4 to 5 repeat units spaced every 21 repeat units along the (1->3)-linked polymer backbone. Computer modeling suggests that the side chains have a bent curve structure that allows for a flexible interconnection with parallel (1->3)-beta-D-glucan polymers, and/or as a point of attachment for proteins. Based on these observations we propose new approaches to how (1->6)-beta-linked side chains interconnect with neighboring glucan polymers in a manner that maximizes fungal cell wall strength, while also allowing for flexibility, or plasticity. PMID- 22096605 TI - Interleukin-6 synthesis in human chondrocytes is regulated via the antagonistic actions of prostaglandin (PG)E2 and 15-deoxy-Delta(12,14)-PGJ2. AB - BACKGROUND: Elevated levels of interleukin-6 (IL-6), prostaglandin (PG)E(2), PGD(2) and its dehydration end product 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) have been detected in joint synovial fluids from patients with rheumatoid arthritis (RA). PGE(2) directly stimulates IL-6 production in human articular chondrocytes. However, the effects of PGD(2) and 15d-PGJ(2) in the absence or presence of PGE(2) on IL-6 synthesis in human chondrocytes have yet to be determined. It is believed that dysregulated overproduction of IL-6 is responsible for the systemic inflammatory manifestations and abnormal laboratory findings in RA patients. METHODOLOGY/PRINCIPAL FINDINGS: Using the T/C-28a2 chondrocyte cell line as a model system, we report that exogenous PGE(2) and PGD(2)/15d-PGJ(2) exert antagonistic effects on IL-6 synthesis in human T/C-28a2 chondrocytes. Using a synthesis of sophisticated molecular biology techniques, we determined that PGE(2) stimulates Toll-like receptor 4 (TLR4) synthesis, which is in turn responsible for the activation of the ERK1/2, PI3K/Akt and PKA/CREB pathways that phosphorylate the NF-kappaB p65 subunit leading to NF-kappaB activation. Binding of the activated NF-kappaB p65 subunit to IL-6 promoter induces IL-6 synthesis in human T/C28a2 chondrocytes. PGD(2) or 15d-PGJ(2) concurrently downregulates TLR4 and upregulates caveolin-1, which in turn inhibit the PGE(2)-dependent ERK1/2, PI3-K and PKA activation, and ultimately with NF kappaB-dependent IL-6 synthesis in chondrocytes. CONCLUSIONS/SIGNIFICANCE: We have delineated the signaling cascade by which PGE(2) and PGD(2)/15d-PGJ(2) exert opposing effects on IL-6 synthesis in human chondrocytes. Elucidation of the molecular pathway of IL-6 synthesis and secretion by chondrocytes will provide insights for developing strategies to reduce inflammation and pain in RA patients. PMID- 22096606 TI - The repetitive cytoskeletal protein H49 of Trypanosoma cruzi is a calpain-like protein located at the flagellum attachment zone. AB - BACKGROUND: Trypanosoma cruzi has a single flagellum attached to the cell body by a network of specialized cytoskeletal and membranous connections called the flagellum attachment zone. Previously, we isolated a DNA fragment (clone H49) which encodes tandemly arranged repeats of 68 amino acids associated with a high molecular weight cytoskeletal protein. In the current study, the genomic complexity of H49 and its relationships to the T. cruzi calpain-like cysteine peptidase family, comprising active calpains and calpain-like proteins, is addressed. Immunofluorescence analysis and biochemical fractionation were used to demonstrate the cellular location of H49 proteins. METHODS AND FINDINGS: All of H49 repeats are associated with calpain-like sequences. Sequence analysis demonstrated that this protein, now termed H49/calpain, consists of an amino terminal catalytic cysteine protease domain II, followed by a large region of 68 amino acid repeats tandemly arranged and a carboxy-terminal segment carrying the protease domains II and III. The H49/calpains can be classified as calpain-like proteins as the cysteine protease catalytic triad has been partially conserved in these proteins. The H49/calpains repeats share less than 60% identity with other calpain-like proteins in Leishmania and T. brucei, and there is no immunological cross reaction among them. It is suggested that the expansion of H49/calpain repeats only occurred in T. cruzi after separation of a T. cruzi ancestor from other trypanosomatid lineages. Immunofluorescence and immunoblotting experiments demonstrated that H49/calpain is located along the flagellum attachment zone adjacent to the cell body. CONCLUSIONS: H49/calpain contains large central region composed of 68-amino acid repeats tandemly arranged. They can be classified as calpain-like proteins as the cysteine protease catalytic triad is partially conserved in these proteins. H49/calpains could have a structural role, namely that of ensuring that the cell body remains attached to the flagellum by connecting the subpellicular microtubule array to it. PMID- 22096607 TI - p21-Activated kinase 1 (Pak1) phosphorylates BAD directly at serine 111 in vitro and indirectly through Raf-1 at serine 112. AB - BACKGROUND: Cell survival depends on the balance between protective and apoptotic signals. When the balance of signals tips towards apoptosis, cells undergo programmed cell death. This balance has profound implications in diseases including cancer. Oncogenes and tumor suppressors are mutated to promote cell survival during tumor development, and many chemotherapeutic drugs kill tumor cells by stimulating apoptosis. BAD is a pro-apoptotic member of the Bcl-2 family of proteins, which can be phosphorylated on numerous sites to modulate binding to Bcl-2 and 14-3-3 proteins and inhibit its pro-apoptotic activities. One of the critical phosphorylation sites is the serine 112 (S112), which can be phosphorylated by several kinases including Pak1. METHODOLOGY/PRINCIPAL FINDINGS: We mapped the Pak phosphorylation sites by making serine to alanine mutations in BAD and testing them as substrates in in vitro kinase assays. We found that the primary phosphorylation site is not S112 but serine 111 (S111), a site that is sometimes found phosphorylated in vivo. In transfection assays of HEK293T cells, we showed that Pak1 required Raf-1 to stimulate phosphorylation on S112. Mutating either S111 or S112 to alanine enhanced binding to Bcl-2, but the double mutant S111/112A bound better to Bcl-2. Moreover, BAD phosphorylation at S111 was observed in several other cell lines, and treating one of them with the Pak1 inhibitor 2,2'-Dihydroxy-1,1'-dinaphthyldisulfide (IPA-3) reduced phosphorylation primarily at S112 and to a smaller extent at S111, while Raf inhibitors only reduced phosphorylation at S112. CONCLUSION/SIGNIFICANCE: Together, these findings demonstrate that Pak1 phosphorylates BAD directly at S111, but phosphorylated S112 through Raf-1. These two sites of BAD serve as redundant regulatory sites for Bcl-2 binding. PMID- 22096608 TI - Post-traumatic stress disorder (PTSD) symptoms predict delay to hospital in patients with acute coronary syndrome. AB - BACKGROUND: Increased delay to hospital presentation with acute coronary syndrome (ACS) is associated with poor outcomes. While demographic factors associated with this delay have been well described, scarce data are available on the role of modifiable factors, such as psychosocial disorders, on pre-hospital delay. Patients with symptoms of post-traumatic stress disorder (PTSD) often avoid stressful situations and may delay presenting for care when they experience cardiac symptoms. It is unknown, however, whether PTSD symptoms negatively impact the time to presentation during an ACS. METHODS: We assessed the relationship between PTSD symptoms and pre-hospital delay in 241 adults with an ACS in the ongoing Prescription Use, Lifestyle, Stress Evaluation (PULSE) study. RESULTS: Overall, 66% of patients were male; 40% were Hispanic or Latino. The mean age was 61.9+/-11.6 years old. PTSD symptoms were present in 17.8% of patients. Pre hospital delay was longer for patients with PTSD symptoms compared to those without [geometric mean: 25.8 hours (95% CI 13.8-44.8) vs. 10.7 hours (95% CI 8.3 13.8)]; P = 0.005. After multivariable adjustment for age, sex, ethnicity, depression, left ventricular ejection fraction and history of myocardial infarction, the mean pre-hospital delay was 173% (95% CI: 36%-450%) longer for patients with versus without PTSD symptoms. CONCLUSION: Among patients presenting with an ACS, PTSD symptoms were independently associated with longer pre-hospital delays. Future studies of pre-hospital delay should examine the mechanisms underlying this association. PMID- 22096609 TI - The effects of warming and nitrogen addition on soil nitrogen cycling in a temperate grassland, northeastern China. AB - BACKGROUND: Both climate warming and atmospheric nitrogen (N) deposition are predicted to affect soil N cycling in terrestrial biomes over the next century. However, the interactive effects of warming and N deposition on soil N mineralization in temperate grasslands are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: A field manipulation experiment was conducted to examine the effects of warming and N addition on soil N cycling in a temperate grassland of northeastern China from 2007 to 2009. Soil samples were incubated at a constant temperature and moisture, from samples collected in the field. The results showed that both warming and N addition significantly stimulated soil net N mineralization rate and net nitrification rate. Combined warming and N addition caused an interactive effect on N mineralization, which could be explained by the relative shift of soil microbial community structure because of fungal biomass increase and strong plant uptake of added N due to warming. Irrespective of strong intra- and inter-annual variations in soil N mineralization, the responses of N mineralization to warming and N addition did not change during the three growing seasons, suggesting independence of warming and N responses of N mineralization from precipitation variations in the temperate grassland. CONCLUSIONS/SIGNIFICANCE: Interactions between climate warming and N deposition on soil N cycling were significant. These findings will improve our understanding on the response of soil N cycling to the simultaneous climate change drivers in temperate grassland ecosystem. PMID- 22096610 TI - Evaluation of approaches to identify the targets of cellular immunity on a proteome-wide scale. AB - BACKGROUND: Vaccine development against malaria and other complex diseases remains a challenge for the scientific community. The recent elucidation of the genome, proteome and transcriptome of many of these complex pathogens provides the basis for rational vaccine design by identifying, on a proteome-wide scale, novel target antigens that are recognized by T cells and antibodies from exposed individuals. However, there is currently no algorithm to effectively identify important target antigens from genome sequence data; this is especially challenging for T cell targets. Furthermore, for some of these pathogens, such as Plasmodium, protein expression using conventional platforms has been problematic but cell-free in vitro transcription translation (IVTT) strategies have recently proved successful. Herein, we report a novel approach for proteome-wide scale identification of the antigenic targets of T cell responses using IVTT products. PRINCIPAL FINDINGS: We conducted a series of in vitro and in vivo experiments using IVTT proteins either unpurified, absorbed to carboxylated polybeads, or affinity purified through nickel resin or magnetic beads. In vitro studies in humans using CMV, EBV, and Influenza A virus proteins showed antigen-specific cytokine production in ELIspot and Cytometric Bead Array assays with cells stimulated with purified or unpurified IVTT antigens. In vitro and in vivo studies in mice immunized with the Plasmodium yoelii circumsporozoite DNA vaccine with or without IVTT protein boost showed antigen-specific cytokine production using purified IVTT antigens only. Overall, the nickel resin method of IVTT antigen purification proved optimal in both human and murine systems. CONCLUSIONS: This work provides proof of concept for the potential of high throughput approaches to identify T cell targets of complex parasitic, viral or bacterial pathogens from genomic sequence data, for rational vaccine development against emerging and re-emerging diseases that pose a threat to public health. PMID- 22096611 TI - Bridging the gap between preclinical and clinical microbicide trials: blind evaluation of candidate gels in murine models of efficacy and safety. AB - BACKGROUND: Despite significant protection in preclinical studies, cellulose sulfate (CS) failed to protect women against HIV-1/2 and was associated with a trend toward increased HIV-1 acquisition in one of the clinical trials. These results highlight the need for preclinical tests more predictive of clinical outcomes. The objective of this study was to test coded vaginal gels, including CS, in murine models of safety and efficacy to determine the models' utility for evaluating future products. METHODS: Four coded formulations, including 6% CS, 2% PRO 2000 and two placebo gels, were administered intravaginally to medroxyprogesterone-treated mice and their ability to prevent genital herpes (efficacy) or to alter the susceptibility to low dose HSV challenge (safety) was determined. Nonoyxnol-9 served as a positive toxicity control. RESULTS: CS and PRO 2000 significantly protected mice from genital herpes following infection with a laboratory or clinical isolate of HSV-2 introduced in buffer (p<0.001). However, protection was reduced when virus was introduced in seminal plasma. Moreover, mice were significantly more susceptible to infection with low doses of HSV-2 when challenged 12 h after the 7th daily dose of CS or nonoxynol-9 (p<0.05). The increased susceptibility was associated with alterations in epithelial architecture. CONCLUSIONS: CS prevented genital herpes when present at the time of viral challenge, but increased the rate of infection when gel was applied daily for 7 days with a vaginal wash prior to viral inoculation. The findings presumably reflect altered epithelial architecture, which may have contributed to the trend towards increased HIV observed clinically. PMID- 22096612 TI - Dynamic microtubules promote synaptic NMDA receptor-dependent spine enlargement. AB - Most excitatory synaptic terminals in the brain impinge on dendritic spines. We and others have recently shown that dynamic microtubules (MTs) enter spines from the dendritic shaft. However, a direct role for MTs in long-lasting spine plasticity has yet to be demonstrated and it remains unclear whether MT-spine invasions are directly influenced by synaptic activity. Lasting changes in spine morphology and synaptic strength can be triggered by activation of synaptic NMDA receptors (NMDARs) and are associated with learning and memory processes. To determine whether MTs are involved in NMDAR-dependent spine plasticity, we imaged MT dynamics and spine morphology in live mouse hippocampal pyramidal neurons before and after acute activation of synaptic NMDARs. Synaptic NMDAR activation promoted MT-spine invasions and lasting increases in spine size, with invaded spines exhibiting significantly faster and more growth than non-invaded spines. Even individual MT invasions triggered rapid increases in spine size that persisted longer following NMDAR activation. Inhibition of either NMDARs or dynamic MTs blocked NMDAR-dependent spine growth. Together these results demonstrate for the first time that MT-spine invasions are positively regulated by signaling through synaptic NMDARs, and contribute to long-lasting structural changes in targeted spines. PMID- 22096613 TI - Android fat depot is more closely associated with metabolic syndrome than abdominal visceral fat in elderly people. AB - BACKGROUND: Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. METHODS AND FINDINGS: As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9+/-8.6 years and 278 female, 76.0+/-8.8 years) with regional body composition data using Dual energy X ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4+/-65.5 cm(2) and 126.9+/-55.2 cm(2) in men (P = 0.045) and 120.0+/-46.7 cm(2) and 211.8+/-65.9 cm(2) in women (P<0.01). Mean android and gynoid fat amount was 1.8+/-0.8 kg and 2.5+/-0.8 kg in men and 2.0+/-0.6 kg and 3.3+/-0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. CONCLUSIONS: Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution. PMID- 22096614 TI - Comparison of peritoneal adhesion formation in bowel retraction by cotton towels versus the silicone lap pak device in a rabbit model. AB - OBJECTIVE: Manipulation of cotton operating room towels within the abdominal cavity in open abdominal surgery has been associated with the formation of peritoneal adhesions. In a rabbit model, the use of standard cotton operating room towels is compared to the Lap Pak, a silicone bowel-packing device, to determine the potential for reducing the risk of adhesions. METHODS: Thirty rabbits were randomly assigned to 3 groups. The rabbits underwent a sham surgery with incision only (n = 10), placement of operating room towels (n = 10), or placement of a Lap Pak (n = 10). After 14 days, the rabbits were sacrificed and the peritoneal cavity explored for adhesions. The number, tenacity, ease of dissection, and density of adhesions were recorded, and the adhesions quantitatively graded using a Modified Hopkins Adhesion scoring system. RESULTS: The operating room towel group had an average adhesion score of 2.5, and 8 (80%) rabbits developed adhesions. The sham group had an average adhesion score of 0.3 and one rabbit (10%) developed adhesions. The Lap Pak group had an average adhesion score of 0.2 and 1 rabbit (10%) developed adhesions. The frequency and severity of adhesions in the operating room towel group were significantly greater from that of the baseline sham group. There was no significant difference between the Lap Pak and sham groups. CONCLUSIONS: In this rabbit laparotomy model, the use of the Lap Pak to retract the bowels resulted in significantly fewer adhesions compared to cotton operating room towels. Lap Pak may be beneficial for bowel packing in general abdominal surgeries. PMID- 22096615 TI - Flexor pollicis longus tendon rupture after volar plating of a distal radius fracture: pronator quadratus plate coverage may not adequately protect tendons. AB - OBJECTIVE: The senior author previously reported a case of rupture of the flexor policis longus tendon after volar plating of a distal radius fracture. We hypothesized that restoration of the pronator quadratus to its native position after plating might prevent this problem. METHODS: The authors report a new case of irritation of the flexor policis longus 2.5 years after volar plating of a distal radius fracture. The plate was in good contact with the bone, and the pronator quadratus had been restored to its native position. Despite this, there was a partial-thickness laceration of the tendon over the plate and a defect in the pronator quadratus muscle which had been between the plate and the tendon. RESULTS: The patient was treated with removal of the plate and repair of the tendon. She never lost function of the flexor policis longus tendon and has full function of her hand. CONCLUSIONS: The authors believe that restoration of the pronator quadratus to its native position after volar plating of a distal radius fracture does protect the overlying flexor tendons. Even with this step, tendon irritation can still occur. The authors advise their patients at the time of discharge from initial treatment of their distal radius fracture to be vigilant for any evidence of flexor tendon irritation and to return for evaluation if they have any suspicion of this. PMID- 22096616 TI - Nitazoxanide Disrupts Membrane Potential and Intrabacterial pH Homeostasis of Mycobacterium tuberculosis. AB - Nitazoxanide (Alinia((r))), a nitro-thiazolyl antiparasitic drug, kills diverse microorganisms by unknown mechanisms. Here we identified two actions of nitazoxanide against Mycobacterium tuberculosis (Mtb): disruption of Mtb's membrane potential and pH homeostasis. Both actions were shared by a structurally related anti-mycobacterial compound, niclosamide. Reactive nitrogen intermediates were reported to synergize with nitazoxanide and its deacetylated derivative tizoxanide in killing Mtb. Herein, however, we could not attribute this to increased uptake of nitazoxanide or tizoxanide as monitored by targeted metabolomics, nor to increased impact of nitazoxanide on Mtb's membrane potential or intrabacterial pH. Thus, further mechanisms of action of nitazoxanide or tizoxanide may await discovery. The multiple mechanisms of action may contribute to Mtb's ultra-low frequency of resistance against nitazoxanide. PMID- 22096617 TI - CONTINUOUS REPOPULATION OF LYMPHOCYTE SUBSETS IN TRANSPLANTED MYCOBACTERIAL GRANULOMAS. AB - Granulomas are the interface between host and mycobacteria, and are crucial for the surivival of both species. While macrophages are the main cellular component of these lesions, different lymphocyte subpopulations within the lesions also play important roles. Lymphocytes are continuously recruited into these inflammatory lesions via local vessels to replace cells that are either dying or leaving; however, their rate of replacement is not known. Using a model of granuloma transplantation and fluorescently labeled cellular compartments we report that, depending on the subpopulation, 10-80%, of cells in the granuloma are replaced within one week after transplantation. CD4(+) T cells specific for Mycobacterium antigen entered transplanted granulomas at a higher frequency than Foxp3(+) CD4(+) T cells by one week. Interestingly, a small number of T lymphocytes migrated out of the granuloma to secondary lymphoid organs. The mechanisms that define the differences in recruitment and efflux behind each subpopulation requires further studies. Ultimately, a better understanding of lymphoid traffic may provide new ways to modulate, regulate, and treat granulomatous diseases. PMID- 22096619 TI - Laparoscopic removal of pelvic hydatid cysts in young female: a case report. AB - Hydatid disease is a zoonotic infection caused by larval stages of dog tapeworms belonging to the genus Echinococcus (family taeniidae) and is also referred to as echinococcosis. Human cystic echinococcosis caused by E. granulosus is the most common presentation and probably accounts for more than 95% of the estimated 2-3 million annual worldwide cases. The liver (70-80%) and lungs (15-25%) are the most frequent locations for echinococcal cysts. The diagnosis is made through the combined assessment of clinical, radiological, and laboratory findings. The treatment is mainly surgical, and, with appropriate diagnosis and treatment, prognosis is good. With advances and increasing experience in laparoscopic surgery, many more attempts have been made to offer the advantage of such a procedure to these patients (Chowbey et al. (2003)). PMID- 22096618 TI - Delineating chromosomal breakpoints in radiation-induced papillary thyroid cancer. AB - Recurrent translocations are well known hallmarks of many human solid tumors and hematological disorders, where patient- and breakpoint-specific information may facilitate prognostication and individualized therapy. In thyroid carcinomas, the proto-oncogenes RET and NTRK1 are often found to be activated through chromosomal rearrangements. However, many sporadic tumors and papillary thyroid carcinomas (PTCs) arising in patients with a history of exposure to elevated levels of ionizing irradiation do not carry these known abnormalities. We developed a rapid scheme to screen tumor cell metaphase spreads and identify candidate genes of tumorigenesis and neoplastic progression for subsequent functional studies. Using a series of overnight fluorescence in situ hybridization (FISH) experiments with pools comprised of bacterial artificial chromosome (BAC) clones, it now becomes possible to rapidly refine breakpoint maps and, within one week, progress from the low resolution Spectral Karyotyping (SKY) maps or Giemsa-banding (G-banding) karyotypes to fully integrated, high resolution physical maps including a list of candiate genes in the critical regions. PMID- 22096620 TI - Single-port Laparoscopic Reversal of Hartmann's Procedure: Technique and Results. AB - In general, reversal of Hartmann's procedure is associated with a high morbidity and therefore leads to a low rate of intestinal restoration. Reversal of Hartmann's procedure has to be seen as a complex abdominal operation with the same possible complications as in other colorectal resections. By using the laparoscopic technique, operative access trauma by laparotomy can be minimized. After introducing single-port access into laparoscopic surgery beginning with cholecystectomies and sigmoid resections, we started with the first single-port laparoscopic reversal of Hartmann's procedure in January 2010. After excision of the colostoma, mobilization, and reponing into the abdominal cavity, the single port trocar was placed at the stoma incision without any extra scar. We investigated whether the single-port laparoscopic reversal is as safely feasible as the "conventional" laparoscopic procedure. Till December 2010, single-port reversal operation was performed in 8 patients 2-4 months after Hartmann's procedure because of complicated diverticulitis. No conversion to "conventional" laparoscopic or open procedure was necessary in 1 patient one extra 5 mm trocar was used. The average operation time was 74 min. Except for one wound complication, the postoperative course was uncomplicated. The patients were discharged after 4 to 8 postoperative days. Single-port reversal of Hartmann's procedure has showed as a new method for minimizing the access trauma even further than "conventional" laparoscopic surgery. PMID- 22096621 TI - The arthroscopic ulnohumeral arthroplasty: from mini-open to arthroscopic surgery. AB - In cubarthritis-osteoarthritis of the elbow-surgical procedures may be considered to debride the elbow joint to reduce pain, to increase mobility, and to postpone joint replacement surgery. The ulnohumeral arthroplasty as described by Outerbridge and Kashiwagi was originally introduced to debride both anterior and posterior elbow compartments through a direct posterior mini-open approach. To achieve this, a distal humeral fenestration throughout the humeral fossa is performed. Although with an elbow arthroscopy, a technique that was obviously developed later on, all compartments can be easily visualized. The arthroscopic fenestration of the humerus preserves its advantages, with good clinical results focused on pain relief and gaining mobility. On top, future elbow joint locking based on degenerative loose bodies can be prevented. Therefore, this surgery is often done in young, more active patients and even in sportsmen. These patients, however, need to be prompted to restrict loading on the elbow in the immediate postoperative period, because the elbow is biomechanically weakened and may be prone to a fracture. However, both outcome and postoperative rehabilitation are promising and the arthroscopic Outerbridge procedure is a reliable procedure with an easy rehabilitation. Therefore, the threshold is relatively low in early cubarthritis and recurrent locking of the elbow. In this paper, we present a literature review and the author's experience and own research on the Outerbridge procedure. PMID- 22096622 TI - 5'CAG and 5'CTG Repeats Create Differential Impediment to the Progression of a Minimal Reconstituted T4 Replisome Depending on the Concentration of dNTPs. AB - Instability of repetitive sequences originates from strand misalignment during repair or replicative DNA synthesis. To investigate the activity of reconstituted T4 replisomes across trinucleotide repeats (TNRs) during leading strand DNA synthesis, we developed a method to build replication miniforks containing a TNR unit of defined sequence and length. Each minifork consists of three strands, primer, leading strand template, and lagging strand template with a 5' single stranded (ss) tail. Each strand is prepared independently, and the minifork is assembled by hybridization of the three strands. Using these miniforks and a minimal reconstituted T4 replisome, we show that during leading strand DNA synthesis, the dNTP concentration dictates which strand of the structure-forming 5'CAG/5'CTG repeat creates the strongest impediment to the minimal replication complex. We discuss this result in the light of the known fluctuation of dNTP concentration during the cell cycle and cell growth and the known concentration balance among individual dNTPs. PMID- 22096623 TI - Serial Assessment of Cardiac Function during and following Mitoxantrone Infusion in 30 Consecutive Patients with Multiple Sclerosis. AB - Immunosuppressive therapy is an established therapeutic option in patients suffering from multiple sclerosis (MS). In an open nonrandomized study we serially assessed cardiac function in 30 consecutive patients with MS before, during, and after mitoxantrone therapy. Mitoxantrone (12 mg/m(2)) was administered intravenously at 3-month intervals. Before each infusion, cardiac function was assessed by history taking, resting electrocardiogram, and echocardiography. Whereas no patient experienced clinical signs of heart failure, left ventricular pump function decreased continuously during mitoxantrone therapy and did not recover after cessation. The presented data suggest a dose-dependent and long-lasting toxic cardiac effect of low-dose mitoxantrone therapy in MS. PMID- 22096624 TI - Phosphorylated neurofilament heavy chain correlations to visual function, optical coherence tomography, and treatment. AB - Objective. To correlate visual and neurologic clinical scores and treatment of optic neuritis and multiple sclerosis (MS) patients with assays of serum phosphorylated neurofilament heavy chain (pNF-H) and optical coherence tomography (OCT) measurements of axonal loss. Design/Methods. The Optic Neuritis Treatment Trial (ONTT) randomized 457 patients with acute optic neuritis to intravenous methylprednisolone (IVMP) followed by oral prednisone, oral prednisone or placebo treatment arms. We quantified serum pNF-H levels in 175 ONTT patients 5 years after study entry. We performed OCT measurements of macular volume and the retinal nerve fiber layer (RNFL) in a subset of 51 patients at year 15. Results. Elevated pNF-H levels at year 5 correlated to poorer visual function at study entry. Lower 15 year macular volumes and RNFL thickness correlated better with follow-up than with baseline visual function measures. With IVMP treatment, 15 year RNFL differences of the fellow eye (FE) minus the affected eye (SE) RNFLFEmSE correlated with five-year pNF-H levels. PNF-H was reduced by half with IVMP relative to placebo or by 40% relative to prednisone. Conclusions/Relevance. Acute optic neuritis patients who have more severe visual loss during initial presentation have a higher incidence of axonal loss that was slightly suppressed with IVMP treatment. PMID- 22096625 TI - Internet usage by patients with multiple sclerosis: implications to participatory medicine and personalized healthcare. AB - Online health information and services for patients were suggested to improve symptom management and treatment adherence, thereby contributing to healthcare optimization. This paper aimed to characterize multiple sclerosis (MS) patients Internet usage. Information regarding browsing habits, Internet reliability, and the medical team's attitude to information collected online was obtained by questionnaires from MS patients. Data was compared between nonbrowsers, browsers on MS topics, and browsers on non-MS topics only. From the 96 patients recruited, 61 (63.5%) performed MS-related searches. The most viewed topics were "understanding the disease" and "treatments". Patients reported that the information helped coping with MS and assured them of the appropriateness of their therapy. Shorter disease duration was correlated with higher Internet activity. Disabled patients were more interested in online interaction with specialists and support groups. This paper suggests that MS patients benefit from online information, and it emphasizes the importance of resources tailored to patients needs. PMID- 22096626 TI - Evaluating the use of optical coherence tomography in optic neuritis. AB - Optic neuritis (ON) is an inflammatory optic nerve injury, which is strongly associated with multiple sclerosis (MS). Axonal damage in the optic nerve manifests as retinal nerve fiber layer (RNFL) deficits, which can be readily quantified with optical coherence tomography (OCT). The RNFL represents the most proximal region of the afferent visual pathway; and, as such, is a unique region of the central nervous system (CNS) because it lacks myelin. Changes in retinal integrity can be correlated with reliable and quantifiable visual outcomes to provide a structural-functional paradigm of CNS injury. Because the eye provides a unique "view" into the effects of CNS inflammation, the ON "system model" may provide greater understanding about disease mechanisms, which underpin disability in MS. This review addresses the applications of OCT in study of ON patients, with specific reference to the published reports to date. The future role of OCT is discussed, both in terms of the potential gains and certain challenges associated with this evolving technology. PMID- 22096627 TI - CCR5Delta32 Polymorphism Associated with a Slower Rate Disease Progression in a Cohort of RR-MS Sicilian Patients. AB - Multiple sclerosis (MS) disease is carried through inflammatory and degenerative stages. Based on clinical feaures, it can be subdivided into three groups: relapsing-remitting MS, secondary progressive MS, and primary progressive MS. Multiple sclerosis has a multifactorial etiology with an interplay of genetic predisposition, environmental factors, and autoimmune inflammatory mechanism in which play a key role CC-chemokines and its receptors. In this paper, we studied the frequency of CCR5 gene Delta32 allele in a cohort of Sicilian RR-MS patients comparing with general Sicilian population. Also, we evaluate the association between this commonly polymorphism and disability development and age of disease onset in the same cohort. Our results show that presence of CCR5Delta32 is significantly associated with expanded disability status scale score (EDSS) but not with age of disease onset. PMID- 22096628 TI - Serum metabolic profile in multiple sclerosis patients. AB - Multiple sclerosis (MS) is a progressive demyelinating process considered as an autoimmune disease, although the causes of this pathology have not been yet fully established. Similarly to other neurodegenerations, MS is characterized by a series of biochemical changes affecting to different extent neuronal functions; great attention has been given to oxidative/nitrosative stress and to alterations in mitochondrial functions. According to previous data, MS patients show significant changes in the circulating concentrations of different metabolites, although it is still unclear whether uric acid undergoes to decrease, increase, or no change under this pathological condition. In this study, we report the serum metabolic profile in terms of purines, pyrimidines, creatinine, malondialdehyde, ascorbic acid, nitrite, and nitrate in a group of 170 MS patients. The results show increase in circulating uric acid and other oxypurines (hypoxanthine and xanthine), as well as in uridine and beta-pseudouridine. The concomitant increase in circulating creatinine, malondialdehyde, nitrite, and nitrate, and decrease in ascorbic acid, demonstrates that MS induces alteration in energy metabolism and in oxidants/antioxidants balance that can be monitored in serum of MS patients. PMID- 22096629 TI - Varicella zoster virus and relapsing remitting multiple sclerosis. AB - Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS. PMID- 22096630 TI - Repeated intrathecal triamcinolone acetonide administration in progressive multiple sclerosis: a review. AB - At the present time, anti-inflammatory, immunomodulatory, or immunosuppressive treatments of multiple sclerosis (MS) are mainly effective in the early phases of the disease but are of less advantage in progressive phases. Current therapeutic strategies of both primary and secondary progressive MS are rare. One alternative may be intrathecal application of triamcinolone acetonide (TCA). Number of papers deal with advantages and disadvantages of intrathecal administration in MS. Former trials lacked detailed selection of MS patients, with small sample sizes, low steroid dosages, and only a small number of intrathecal administration of short acting steroids. The present paper summarizes recent trials performed following a different treatment regime. They were conducted in patients with progressive MS suffering mainly from spinal symptoms and documented a significant improvement of EDSS and walking distance (WD). Intrathecal TCA administration is a proposal to take into account as one therapy option in patients with a progressive clinical course and predominantly spinal symptoms. PMID- 22096631 TI - Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker Studies. AB - There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF) are being used in clinical practice. Anti-aquaporin 4 antibodies in serum are currently useful for the diagnosis of neuromyelitis optica (NMO), but we could expect novel CSF biomarkers that help define prognosis and response to treatment for this disease. One of the most critical factors in biomarker research is the inadequate powering of studies performed by single centers. Collaboration between investigators is needed to establish large biobanks of well-defined samples. A key issue in collaboration is to establish standardized protocols for biobanking to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by pre-analytical factors. Here, consensus guidelines for CSF collection and biobanking are presented, based on the guidelines that have been published by the BioMS-eu network for CSF biomarker research. We focussed on CSF collection procedures, pre analytical factors and high quality clinical and paraclinical information. Importantly, the biobanking protocols are applicable for CSF biobanks for research targeting any neurological disease. PMID- 22096632 TI - The impact of comorbid depression on adherence to therapy for multiple sclerosis. AB - Objective. Examine the impact of comorbid depression on adherence to disease modifying therapy (DMT) for multiple sclerosis (MS). Methods. A retrospective database was used to identify patients with MS treated with a DMT. Patients with MS and comorbid depression were matched to patients with MS only. Adherence to DMT was proxied by the medication possession ratio (MPR) and multivariate regressions were used to examine the association between comorbid depression and adherence to DMT. Results. Patients with comorbid depression had a 10 point lower MPR (P < 0.01) and were less likely to achieve a MPR of at least 80% (odds ratio (OR) = 0.55; 95% confidence interval (CI) 0.42-0.74) than those without depression. While treatment with an antidepressant generally had no significant impact on the likelihood of achieving an MPR threshold of 80% (OR = 1.32; 95% CI 0.50-3.48), adherence to antidepressant therapy guidelines were associated with improved adherence to DMT therapy. Conclusions. MS patients with comorbid depression were approximately half as likely to be adherent to their DMT relative to patients with MS without depression. Although treatment with antidepressant therapy generally did not improve the likelihood of adherence, treatment with antidepressants for at least 6 months was associated with better adherence to DMT. PMID- 22096633 TI - Exploring the Association between Retinal Nerve Fiber Layer Thickness and Initial Magnetic Resonance Imaging Findings in Patients with Acute Optic Neuritis. AB - Background. Recent studies have shown that OCT-measured retinal nerve fiber layer (RNFL) values may represent a marker for axonal damage in the anterior visual pathway of optic neuritis (ON) and multiple sclerosis (MS) patients. The goal of this study was to determine the link between RNFL values and initial magnetic resonance imaging (MRI) evidence of central nervous system (CNS) inflammation in patients with acute ON. Methods. Fifty patients who experienced ON as a clinically isolated syndrome (CIS) were followed for a mean period of 34 months with OCT testing. RNFL values in affected (ON) eyes and clinically unaffected (non-ON) eyes were compared between patients with MRI evidence of white matter lesions and those with normal baseline MRI findings, over a two year period. Findings. Twenty-one patients (42%) developed clinically definite MS (CDMS) during the study. After two years, temporal RNFL values were thinner (P = .07) in ON patients with MRI lesions at baseline, but the results were not significant. Conclusions. There is no association between RNFL values and baseline MRI status in ON patients at risk for future CDMS over a two year period. PMID- 22096634 TI - Corpus callosum microstructural changes correlate with cognitive dysfunction in early stages of relapsing-remitting multiple sclerosis: axial and radial diffusivities approach. AB - The corpus callosum is the largest fiber bundle in the central nervous system and it takes part in several cognitive pathways. It can be affected by multiple sclerosis (MS) early in the disease. DTI is capable of infering the microstructural organization of the white matter. The vectorial analysis of the DTI offers the more specific indices of axial diffusivity (AD) and radial diffusivity (RD), which have shown to be useful to discriminate myelin damage from axon loss, respectively. This study presents DTI results (mean diffusivity (MD), fractional anisotropy (FA), RD, and AD) of 23 relapsing-remitting MS patients and its correlation with cognitive performance. There were 47.8% of cognitive impaired patients (MS CI). We found signs of demyelination, reflected by increased RD, and incipient axon loss, reflected by AD increase, which was slightly higher in the MS CI. The cognitive changes correlated with the DTI parameters, suggesting that loss of complexity in CC connections can impair neural conduction. Thus, cognitive impairment can be related to callosal disconnection, and DTI can be a promising tool to evaluate those changes. PMID- 22096635 TI - Neurofilament proteins as body fluid biomarkers of neurodegeneration in multiple sclerosis. AB - Biomarkers of axonal degeneration have the potential to improve our capacity to predict and monitor neurological outcome in multiple sclerosis (MS) patients. Neurofilament proteins, one of the major proteins expressed within neurons and axons, have been detected in cerebrospinal fluid and blood samples from MS patients and are now being actively investigated for their utility as prognostic indicators of disease progression in MS. In this paper, we summarize the current literature on neurofilament structure, assembly, and degeneration and discuss their potential utility as biomarkers for monitoring neurological decline in MS. We also discuss the need to further develop sensitive methods for assaying neurofilaments in blood to improve clinical applicability. PMID- 22096636 TI - Potential impact of B cells on T cell function in multiple sclerosis. AB - Multiple sclerosis is a chronic debilitating autoimmune disease of the central nervous system. The contribution of B cells in the pathoetiology of MS has recently been highlighted by the emergence of rituximab, an anti-CD20 monoclonal antibody that specifically depletes B cells, as a potent immunomodulatory therapy for the treatment of MS. However, a clearer understanding of the impact B cells have on the neuro-inflammatory component of MS pathogenesis is needed in order to develop novel therapeutics whose affects on B cells would be beneficial and not harmful. Since T cells are known mediators of the pathology of MS, the goal of this review is to summarize what is known about the interactions between B cells and T cells, and how current and emerging immunotherapies may impact B-T cell interactions in MS. PMID- 22096637 TI - Multiple sclerosis: a disorder of altered T-cell homeostasis. AB - Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-onset thymic involution that causes reduced thymic output. The reduced thymic output leads to secondary peripheral homeostatic alterations in naive CD4 T-cells, which closely mimic T-cell alterations observed in an experimental animal model of diabetes mellitus. Homeostatic T-cell receptor (TCR) signalling and proliferation of naive T cells are induced by self-peptides. Consequently, the findings of increased TCR signalling of naive CD4 T-cells, without increased proliferation, in PPMS, and the increased homeostatic proliferation of naive CD4 T-cells in RRMS favour the development of autoimmunity. Thus, it seems highly likely that peripheral T-cell alterations secondary to a thymic abnormality contribute to the pathogenesis of both MS subtypes. PMID- 22096638 TI - Optical coherence tomography in multiple sclerosis and neuromyelitis optica: an update. AB - Optical coherence tomography (OCT) uses light interference patterns to produce a cross-sectional image of the retina. It is capable of measuring the unmyelinated axons of the retinal ganglionar cells as they converge on the optic disc. In a disease like multiple sclerosis (MS), in which axonal loss has been identified as an important cause of sustained disability, it may prove an invaluable tool. OCT has demonstrated that axonal loss occurs after each episode of optic neuritis and that the degree of axonal loss is correlated to visual outcomes. Furthermore, axonal loss occurs in MS even in the absence of inflammatory episodes, and the degree of this loss is correlated with the duration of the disease process, with more thinning as the disease advances and in progressive forms. Thus, OCT retinal nerve fiber layer measurements may represent an objective outcome measure with which to evaluate the effect of treatment. PMID- 22096639 TI - Reduced ErbB4 Expression in Immune Cells of Patients with Relapsing Remitting Multiple Sclerosis. AB - Background. There is an insufficient remyelination in the lesions of multiple sclerosis (MS). One of the factor that was found to promote remyelination is neuregulin-1 which is the ligand of ErbB4. Immune cells have been implicated in neurogenesis and oligodendrogenesis. Aims. We studied the expression of ErbB4 in the immune cells of patients with relapsing remitting (RR) multiple sclerosis (MS) and healthy controls. Methods. ErB4 expression in immune cells was studied by flow cytometry without stimulation or with stimulation with anti-CD3 and anti CD28 monoclonal antibodies or in the presence of interferon-g or TNF-alpha as well as by immunoprecipitation and Western blot, and its mRNA was studied by real time PCR. Results. We found reduced levels of ErbB4 in the total PBMCs and in T cells, monocytes, and B cells of RR MS patients. Similarly, the ErbB4 RNA levels were reduced in the immune cells of patients with RR-MS. Stimulation via CD3 and CD28 significantly upregulated the expression of ErbB4 on immune cells healthy individuals. This effect was weaker in the patients group. Conclusion. ErbB4 may play a role in the proliferation of oligodendrocyte progenitor cells, differentiation of oligodendrocytes, and remyelination, and, therefore, the reduced ErbB4 expression in immune cells of patients with RR-MS may contribute to insufficient remyelination that occurs in the disease. PMID- 22096640 TI - Iron and neurodegeneration in multiple sclerosis. AB - Increased iron deposition might be implicated in multiple sclerosis (MS). Recent development of MRI enabled to determine brain iron levels in a quantitative manner, which has put more interest on studying the role of iron in MS. Evidence for abnormal iron homeostasis in MS comes also from analyses of iron and iron related proteins in CSF and blood and postmortem MS brain sections. However, it is not yet clear if iron accumulation is implicated in MS pathology or merely reflects an epiphenomenon. Further interest has been generated by the idea of chronic cerebrospinal venous insufficiency that might be associated with brain iron accumulation due to a reduction in venous outflow, but its existence and etiologic role in MS are currently controversially debated. In future studies, combined approaches applying quantitative MRI together with CSF and serum analyses of iron and iron-related proteins in a clinical followup setting might help to elucidate the implication of iron accumulation in MS. PMID- 22096641 TI - When to initiate disease-modifying drugs for relapsing remitting multiple sclerosis in adults? AB - For patients with Relapsing Remitting Multiple Scierosis Beta Interfaerons and Glatiramer Acetate were the first to be licensed for treatment. This review deals with one major question: when to initiate therapy? Through exploring the unique characteristics of the disease and treatement we suggest an approach that should be helpful in the process of decision-making. PMID- 22096643 TI - Hyperacute corticosteroid treatment of optic neuritis at the onset of pain may prevent visual loss: a case series. AB - Aim. To show that high-dose corticosteroids may prevent visual loss in patients with optic neuritis (ON) treated at the prodromal, hyperacute, phase of retrobulbar pain. Method. Prospective case series: patients were recruited with a history of ON associated with pain. The patients were advised to report immediately to the investigators should the pain recur in either eye. Where possible, orbital magnetic resonance imaging (MRI) was performed to confirm a recurrence of ON and treatment with high-dose corticosteroids was commenced. Visual function and the patient's subjective account were monitored. Results. Eight patients (including cases of MS, CRION and NMO) presented in the hyperacute phase. MRI confirmed optic nerve inflammation in 5/5. Treatment was commenced immediately, and, in all cases, no visual loss ensued. Conclusion. MRI can be used to confirm acute optic neuritis prior to visual loss in the hyperacute phase. We suggest that treatment with high-dose corticosteroids may abort the attack and prevent loss of vision in patients with ON who are treated at the onset of pain. This has potential implications for the management of acute ON and also for our understanding of the pathogenesis and potential therapeutic targets in the neuroinflammatory conditions associated with ON. PMID- 22096644 TI - Blood and CSF Biomarker Dynamics in Multiple Sclerosis: Implications for Data Interpretation. AB - Background. Disability in multiple sclerosis (MS) is related to neuroaxonal degeneration. A reliable blood biomarker for neuroaxonal degeneration is needed. Objectives. To explore the relationship between cerebrospinal fluid (CSF) and serum concentrations of a protein biomarker for neuroaxonal degeneration, the neurofilaments heavy chain (NfH). Methods. An exploratory cross-sectional (n = 51) and longitudinal (n = 34) study on cerebrospinal fluid (CSF) and serum NfH phosphoform levels in patients with MS. The expanded disability status scale (EDSS), CSF, and serum levels of NfH-SMI34 and NfH-SMI35 were quantified at baseline. Disability progression was assessed at 3-year followup. Results. At baseline, patients with primary progressive MS (PPMS, EDSS 6) and secondary progressive MS (SPMS, EDSS 6) were more disabled compared to patients with relapsing remitting MS (RRMS, EDSS 2, P < .0001). Serum and CSF NfH phosphoform levels were not correlated. Baseline serum levels of the NfH-SMI34 were significantly (P < .05) higher in patients with PPMS (2.05 ng/mL) compared to SPMS (0.03 ng/mL) and RRMS (1.56 ng/mL). In SPMS higher serum than CSF NfH-SMI34 levels predicted disability progression from baseline (DeltaEDSS 2, P < .05). In RRMS higher CSF than serum NfH-SMI35 levels predicted disability progression (DeltaEDSS 2, P < .05). Conclusion. Serum and CSF NfH-SMI34 and NfH-SMI35 levels did not correlate with each other in MS. The quantitative relationship of CSF and serum NfH levels suggests that neuroaxonal degeneration of the central nervous system is the likely cause for disability progression in RRMS. In more severely disabled patients with PP/SPMS, subtle pathology of the peripheral nervous system cannot be excluded as an alternative source for blood NfH levels. Therefore, the interpretation of blood protein biomarker data in diseases of the central nervous system (CNS) should consider the possibility that pathology of the peripheral nervous system (PNS) may influence the results. PMID- 22096645 TI - Restless legs syndrome presenting as an acute exacerbation of multiple sclerosis. AB - Restless legs syndrome is common in patients with multiple sclerosis but has not been reported as occurring due to an acute, inflammatory, demyelinating attack. Restless legs syndrome is known to be related to low brain iron levels. Multiple sclerosis has been associated with the abnormal accumulation of iron in the chronic, progressive phase of axonal degeneration. Iron deficiency may play a role in demyelination. This suggests that restless legs syndrome may be caused by the inflammatory, demyelinating component of multiple sclerosis rather than axonal degeneration. The author presents a case of self-limited restless legs syndrome occurring as an acute attack of multiple sclerosis, supporting the notion that inflammatory demyelination is the underlying pathophysiology of restless legs syndrome in multiple sclerosis. PMID- 22096642 TI - Cerebrospinal fluid and blood biomarkers of neuroaxonal damage in multiple sclerosis. AB - Following emerging evidence that neurodegenerative processes in multiple sclerosis (MS) are present from its early stages, an intensive scientific interest has been directed to biomarkers of neuro-axonal damage in body fluids of MS patients. Recent research has introduced new candidate biomarkers but also elucidated pathogenetic and clinical relevance of the well-known ones. This paper reviews the existing data on blood and cerebrospinal fluid biomarkers of neuroaxonal damage in MS and highlights their relation to clinical parameters, as well as their potential predictive value to estimate future disease course, disability, and treatment response. Strategies for future research in this field are suggested. PMID- 22096646 TI - Response to interferon-Beta treatment in afro-caribbeans with multiple sclerosis. AB - Background. Multiple sclerosis (MS) patients of African ancestry have a more aggressive disease course than white patients and could be resistant to interferon-beta (INFB). Methods. We studied the impact of INFB in treatment-naive Afro-Caribbean (AC) with clinically definite MS using our European Database for Multiple Sclerosis (EDMUS) (2003-2010). Main outcome measures were annual relapse rate after 2 years of treatment, proportion of exacerbation-free subjects 48 weeks after initiating INFB, and time to first relapse. Results. 76 AC-MS (59F/17M) were identified. Annual relapse rate of 1.29 decreased to 0.83 (-35.6%) after 2 years of treatment. The proportion of relapse-free patients at 48 weeks was 46.2%. Median time to first relapse was 52 weeks. Conclusion. INFB is not strong enough to control AC-MS patients in many cases which is problematic in a population of worse MS prognosis. PMID- 22096647 TI - An NTCP Analysis of Urethral Complications from Low Doserate Mono- and Bi Radionuclide Brachytherapy. AB - Urethral NTCP has been determined for three prostates implanted with seeds based on (125)I (145 Gy), (103)Pd (125 Gy), (131)Cs (115 Gy), (103)Pd-(125)I (145 Gy), or (103)Pd-(131)Cs (115 Gy or 130 Gy). First, DU(20), meaning that 20% of the urhral volume receive a dose of at least DU(20), is converted into an I-125 LDR equivalent DU(20) in order to use the urethral NTCP model. Second, the propagation of uncertainties through the steps in the NTCP calculation was assessed in order to identify the parameters responsible for large data uncertainties. Two sets of radiobiological parameters were studied. The NTCP results all fall in the 19%-23% range and are associated with large uncertainties, making the comparison difficult. Depending on the dataset chosen, the ranking of NTCP values among the six seed implants studied changes. Moreover, the large uncertainties on the fitting parameters of the urethral NTCP model result in large uncertainty on the NTCP value. In conclusion, the use of NTCP model for permanent brachytherapy is feasible but it is essential that the uncertainties on the parameters in the model be reduced. PMID- 22096648 TI - Comments on the extraperitoneal approach for standard laparoscopic radical prostatectomy: what is gained and what is lost. AB - Laparoscopic extraperitoneal radical prostatectomy (LERP) is considered the standard care treatment option for the management of localized and locally advanced prostatic cancer (PCa) in many institutes worldwide. In this work, the main advantages and disadvantages of LERP approach are reviewed with regard to its outcomes, the complication management, the learning curve, and the extend of pelvic lymph node dissection (PLND). It is concluded that LERP demonstrates comparable cancer control, urinary continence, and potency outcomes with the open and the robot-assisted radical prostatectomy, while offering advantages in complication management in comparison to the transperitoneal approach. Learning curve of LERP is considered long and stiff and significantly affects perioperative outcomes and morbidity, cancer control, and functional results. Thus, close mentoring especially in the beginning of the learning curve is advised. Finally, LERP still has a role in the limited or modified PLND offered in intermediate risk PCa patients. PMID- 22096649 TI - Pathology update for urologists. PMID- 22096650 TI - Racial/Ethnic patterns in prostate cancer outcomes in an active surveillance cohort. AB - Introduction. Concern regarding overtreatment of prostate cancer (CaP) is leading to increased attention on active surveillance (AS). This study examined CaP survivors on AS and compared secondary treatment patterns and overall survival by race/ethnicity. Methods. The study population consisted of CaP patients self classified as black or white followed on AS in the Center for Prostate Disease Research (CPDR) multicenter national database between 1989 and 2008. Secondary treatment included radical prostatectomy (RP), external beam radiation therapy or brachytherapy (EBRT-Br), and hormone therapy (HT). Secondary treatment patterns and overall survival were compared by race/ethnicity. Results. Among 886 eligible patients, 21% were black. Despite racial differences in risk characteristics and secondary treatment patterns, overall survival was comparable across race. RP following AS was associated with the longest overall survival. Conclusion. Racial disparity in overall survival was not observed in this military health care beneficiary cohort with an equal access to health care. PMID- 22096651 TI - First danish single-institution experience with radical prostatectomy: biochemical outcome in 1200 consecutive patients. AB - Radical retropubic prostatectomy (RRP) as intended curative therapy for patients with clinically localized prostate cancer (PC) was initiated in 1995 in Denmark. This paper reports single-institution results from the first 1200 consecutive patients operated during a 15-year period. Median age at surgery was 63 years. Median PSA was 9 ng/mL. Palpable tumors (<=cT2) were present in 48% of patients. Gleason score at biopsy was <=7 for 85% of patients. In sixty-five percent of patients, histopathology revealed localized PCa after RRP. Positive surgical margins were found in 39.2% of the cases. Biochemical recurrence (BR) occurred for 214 (18%) of patients. The estimated biochemical recurrence free survival (BRFS) was 71.7% and 63.2% after 5 and 10 years, respectively. When patients were stratified according to the D'Amico criteria, BRFS after 10 years was 75.3%, 59.7%, and 39.3% for low-, medium- and high-risk patients, respectively. In univariate analysis, clinical stage, PSA at diagnosis and type of surgery were significant predictors of BR. In multivariate analysis, Gleason score > 7, PSA > 10, and higher clinical stage were significant predictors of BR. Early Danish results in a population not subjected to screening demonstrate BRFS rates comparable with earlier reports from the prescreening era. PMID- 22096652 TI - The Metabolic Syndrome and Biochemical Recurrence following Radical Prostatectomy. AB - Metabolic syndrome refers to a set of conditions that increases the risk of cardiovascular disease and has been associated with an increased risk of prostate cancer, particularly among African American men. This study aimed to estimate the association of metabolic syndrome with biochemical recurrence (BCR) in a racially diverse population. Among 383 radical prostatectomy patients, 67 patients had documented biochemical recurrence. Hypertension was significantly, positively associated with the rate of BCR (hazard ratio (HR) = 2.1; 95% CI = 1.1, 3.8). There were distinct racial differences in the prevalence of individual metabolic syndrome components; however, the observed associations with BCR did not differ appreciably by race. We conclude that hypertension may contribute to a poorer prognosis in surgically treated prostate cancer patients. Our findings suggest that targeting components of the metabolic syndrome which are potentially modifiable through lifestyle interventions may be a viable strategy to reduce risk of BCR in prostate cancer. PMID- 22096653 TI - Bevacizumab and weekly docetaxel in patients with metastatic castrate-resistant prostate cancer previously exposed to docetaxel. AB - Background. The aim of this paper was to evaluate the activity and tolerability of docetaxel (D) and bevacizumab (Bev) in patients with metastatic castrate resistant prostate cancer (CRPC) previously exposed to D. Methods. Treatment consisted of D 30 mg/m(2) i.v. for four consecutive weekly administrations followed by a 2-week rest interval, in addition to Bev 5 mg/kg i.v. every 2 weeks. Results. Forty-three patients were enrolled: a PSA response was observed in 27 patients (62.7%, 95% CI: 0.41 to 0.91), and a palliative response was achieved in 31 patients (72.1%, 95%CI: 0.48 to 1.02). After a median followup of 11.3 months, only five patients had died. The regimen was generally well tolerated. Conclusion. Weekly D + biweekly Bev seems to be an effective and well tolerated treatment option for patients with metastatic CRPC previously exposed to D-based chemotherapy. PMID- 22096654 TI - Specimen orientation by marking the peripheral end: (potential) clinical advantages in prostate biopsy. AB - The aim of this paper is to identify advantages that could be obtained by orientation of the biopsy specimen using the marking technique. We reviewed our experience (4,500 cases) and the published literature. The peripheral (proximal) end of the fresh specimen is marked with ink soon after needle delivering in a few minutes. It is performed easily in association with pre-embedding method. Five potential clinical advantages were identified: (1) tumor localization, (2) atypical lesions localization and planning rebiopsy strategy, (3) planning surgical strategy, (4) selection criteria for focal therapy and active surveillance, and (5) cost reduction. Peripheral end marking is low cost, easy and reproducible. It drives several potential advantages in cancer diagnosis or isolated atypical lesions, in particular, spatial localization within the biopsy (transition versus peripheral zone, anterior versus posterior, subcapsular versus intraparenchima, and extraprostatic extension) should be easy and reliable. We can add a new pathological parameter: pathological orientation or biopsy polarity. PMID- 22096655 TI - Using molecular markers to help predict who will fail after radical prostatectomy. AB - Recent phase III trial data clearly demonstrate that adjuvant therapy can reduce recurrence and increase survival after prostatectomy for prostate cancer. There is great interest in being able to accurately predict who is at risk of failure to avoid treating those who may not benefit. The standard markers consisting of prostate specific antigen (PSA), Gleason score, and pathological stage are not very specific, so there is an unmet need for other markers to aid in prognostic stratification. Numerous studies have been conducted with various markers and more recently gene signatures, but it is unclear whether any of them are really useful. We conducted a comprehensive review of the literature to determine the current status of molecular markers in predicting outcome after radical prostatectomy. PMID- 22096656 TI - Proliferative tumor doubling times of prostatic carcinoma. AB - Prostate cancer (PCa) has a variable biology ranging from latent cancer to extremely aggressive tumors. Proliferative activities of cancers may indicate their biological potential. A flow cytometric assay to calculate maximum proliferative doubling times (T(max)) of PCa in radical prostatectomy specimens after preoperative in vivo bromodeoxyuridine (BrdU) infusion is presented. Only 4/17 specimens had tumors large enough for flow cytometric analysis. The T(max) of tumors was similar and ranged from 0.6 to 3.6 months. Tumors had calculated doubling times 2- to 25-fold faster than their matched normal tissue. Variations in labeling index and T(max) were observed within a tumor as well as between different Gleason grades. The observed PSA doubling times (PSA-DT) ranged from 18.4 to 32.0 months, considerably slower than the corresponding T(max) of tumors involved. While lack of data for apoptotic rates is a limitation, apparent biological differences between latent versus aggressive PCa may be attributable to variations in apoptotic rates of these tumors rather than their cell proliferative rates. PMID- 22096657 TI - Systematic analysis of transrectal prostate biopsies using an ink method and specific histopathologic protocol: a prospective study. AB - Background. Transrectal prostate biopsy is the standard protocol for the screening for prostate cancer. It helps to locate prostatic adenocarcinoma and plan treatment. However, the increasing number of prostate biopsies leads to considerably greater costs for the pathology laboratories. In this study, we compare the traditional method with an ink method in combination with a systematic histopathologic protocol. Methods. Two hundred consecutive transrectal prostate biopsy specimens were received from the radiology department. They were separated into two groups: one hundred were processed as six different specimens in the usual manner. The other one hundred were submitted in six containers, the apex, base, and middle section of which were stained different colours. The samples subject to the ink method were embedded in paraffin and placed in two cassettes which were sectioned using a specific protocol. Results. The comparative study of the nonink and ink methods for histopathologic diagnosis showed no statistical differences as far as diagnostic categories were concerned (P value < .005). The number of PIN diagnoses increased when the ink method was used, but no statistical differences were found. The ink method led to a cost reduction of 48.86%. Conclusions. Our ink method combined with a specific histopathologic protocol provided the same diagnostic quality, tumor location information as the traditional method, and lower pathology expenses. PMID- 22096658 TI - ER and PI3K independently modulate endocrine resistance in ER-positive breast cancer. AB - Endocrine therapy-resistant estrogen receptor-positive (ER(+)) breast cancer is the most common cause of breast cancer death. Miller and colleagues demonstrate that ligand-independent ER activity promotes the growth of breast cancer cells through CDK4/E2F. As an independent event, the phosphatidylinositol 3-kinase (PI3K) pathway is also upregulated in endocrine therapy-resistant cells. Promising preclinical evidence by several groups for the combination of an inhibitor of ligand-independent ER, fulvestrant, with PI3K inhibition, has led to the activation of trials evaluating this concept. PMID- 22096660 TI - Are the American Psychological Association's Detainee Interrogation Policies Ethical and Effective?: Key Claims, Documents, and Results. AB - After 9-11, the United States began interrogating detainees at settings such as Abu Ghraib, Bagram, and Guantanamo. The American Psychological Association (APA) supported psychologists' involvement in interrogations, adopted formal policies, and made an array of public assurances. This article's purpose is to highlight key APA decisions, policies, procedures, documents, and public statements in urgent need of rethinking and to suggest questions that may be useful in a serious assessment, such as, "However well intended, were APA's interrogation policies ethically sound?"; "Were they valid, realistic, and able to achieve their purpose?"; "Were other approaches available that would address interrogation issues more directly, comprehensively, and actively, that were more ethically and scientifically based, and that would have had a greater likelihood of success?"; and "Should APA continue to endorse its post-9-11 detainee interrogation policies?" PMID- 22096661 TI - Time for a new approach to case reports. PMID- 22096662 TI - H1N1 infection in emergency surgery: A cautionary tale. AB - Pandemic 2009 influenza A H1N1 has spread rapidly since its first report in Mexico in March 2009. This is the first influenza pandemic in over 40 years and it atypically affects previously healthy young adults, with higher rates of morbidity and mortality. The medical literature has been inundated with reports of H1N1 infection, the majority found in critical care and internal medicine journals with a relative paucity in the surgical literature. Despite this, it remains an important entity that can impact greatly on acute surgical emergencies. We present a case of previously healthy 31-year-old male who underwent open appendectomy. His post-operative recovery was complicated by acute respiratory distress syndrome secondary to H1N1 infection. This case report highlights the impact that H1N1 virus can have on acute surgical emergencies and how it can complicate the post-operative course. PMID- 22096659 TI - The emergence of lncRNAs in cancer biology. AB - The discovery of numerous noncoding RNA (ncRNA) transcripts in species from yeast to mammals has dramatically altered our understanding of cell biology, especially the biology of diseases such as cancer. In humans, the identification of abundant long ncRNA (lncRNA) >200 bp has catalyzed their characterization as critical components of cancer biology. Recently, roles for lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types, such as breast and prostate cancer. In this review, we highlight the emerging impact of ncRNAs in cancer research, with a particular focus on the mechanisms and functions of lncRNAs. PMID- 22096663 TI - No more abdominal hysterectomy for myomata using a new minimally-invasive technique. AB - To perform hysterectomy in uterus myomatosus, there are several surgical techniques. For a uterine weight of >1000 g, after a caesarean section and in nullipara per vaginam, the most common surgical technique for hysterectomy in patients is hysterectomy per laparotomiam. A new endoscopical technique developed to treat such patients and to avoid laparotomy is described in this case report: the laparoscopic combined hysterectomy (LACH) using the change-over technique. Adhesiolysis, preparation of the ureters and the bladder and morcellation of the uterus of 2480 g were performed minimally-invasive in two steps, from one side of the patient with a change-over of the OP-team to the other side of the patient. The cervix was removed per vaginam. PMID- 22096664 TI - Actinomycosis of the colon with invasion of the abdominal wall: An uncommon presentation of a colonic tumour. AB - Actinomycosis is an uncommon chronic suppurative infectious disease that is caused by Actinomycetes organisms, which are gram-positive, microaerophilic, anaerobic bacteria. The most common type causing disease in humans is Actinomyces israelii. This organism is a commensal of the human mouth and is seldom pathogenic. When it does cause disease, however, three main clinical types of involvement are recognized including cervico-facial, thoracic and abdominal actinomycosis.Herein, we present the case of a 79-year-old male patient who underwent surgical exploration following presentation with abdominal pain and an abdominal mass, initially thought to be a malignancy. Pathologic examination confirmed this as a case of abdominal actinomycosis. This diagnosis should always be included in the differential diagnosis of patients who present with an infiltrative abdominal mass. PMID- 22096665 TI - Popliteal artery entrapment syndrome. AB - Popliteal artery entrapment syndrome is a rare abnormality of the anatomical relationship between the popliteal artery and adjacent muscles or fibrous bands in the popliteal fossa. The following is a case report of a 19 year old female, in whom popliteal artery entrapment syndrome was diagnosed, and successfully treated surgically. A review of literature is also presented and provides details on how PAES is classified, diagnosed both clinically and radiologically, and treated surgically. PMID- 22096666 TI - Coexistence of colonic carcinoma, renal cell carcinoma and gastrointestinal stromal tumour-A case report. AB - The occurrence of synchronous primary neoplasms remains an issue of great interest to surgeons and oncologists in particular, and the medical field in general. The question of common genetic pathways in the pathogenesis of such neoplasms is always raised when such associations are seen-whether metachronously or synchronously. The possibility of the coexistence of multiple tumours in the same patient must be taken into consideration when preparing patients for operation and a thorough search of the intraperitoneal organs for such coexistence remains important.A case of synchronously resected caecal carcinoma, jejunal gastrointestinal stromal tumour and renal cell carcinoma is presented here, along with a literature review on synchronous tumour resection. PMID- 22096667 TI - A case of a paraduodenal hernia. AB - Paraduodenal hernias are rare hernias that result from error of rotation of the mid-gut. It can be discovered incidentally at laparotomy, seen on radiological imagining or infrequently cause intestinal obstruction. We report a case of a left paraduodenal hernia diagnosed intraoperatively after being operated on in the emergency setting for generalized peritonitis. He required resection of multiple loops of small bowel with primary anastomosis. The mouth of the sac was obliterated by suture apposition to the posterior wall. The patient was discharged on day 4 after an uneventful recovery. PMID- 22096668 TI - Scrotal calcinosis: A case report. AB - Scrotal calcinosis (SC) was a rare and benign condition characterized by multiple calcific substances deposits occurring in scrotum and formed nodules and lumps within scrotal skin. A case of a 49-year-old male patient with a 7-year history of scrotal calcinosis was reported. Histopathological findings had not showed evidences of epithelial structures. In our case, no evidence of cystic structure was found around calcified materials. It was indicated that SC might be idiopathic. PMID- 22096669 TI - Castleman's disease-A case report. AB - Castleman's disease is a rare clinicopathological entity characterized by non neoplastic lymph node hypertrophy. Its incidence and etiology is unknown. It has been found in association with Kaposi's sarcoma thus necessitating investigations for HIV. Although its localized variety is benign other types can be multifocal with adverse systemic manifestations. A case report of a 42 yrs old female with a slowly enlarging highly vascular mass in the left iliac fossa is presented which lead to a histological diagnosis of this rare condition (see picture). Furthermore its clinical features, its types, relevant investigations and current treatment modalities are discussed. PMID- 22096670 TI - Colonic obstruction secondary to incarcerated Spigelian hernia in a severely obese patient. AB - Spigelian hernia is a rare hernia of the ventral abdominal wall accounting for 1 2% of all hernias. Incarceration of a Spigelian hernia has been reported in 17 24% of the cases. We herein describe an extremely rare case of a colonic obstruction secondary to an incarcerated Spigelian hernia in a severely obese patient. Physical examination was inconclusive and diagnosis was established by computed tomography scans. The patient underwent an open intraperitoneal mesh repair. A high level of suspicion and awareness is required as clinical findings of a Spigelian hernia are often nonspecific especially in obese patients. Computed tomography scan provides detailed information for the surgical planning. Open mesh repair is safe in the emergent surgical intervention of a complicated Spigelian hernia in severely obese patients. PMID- 22096671 TI - Adrenocortical oncocytoma: Review of imaging and histopathological implications. AB - Oncocytomas are rare tumours of the adrenal glands whose malignant potential is difficult to assess with certainty. We report a case of an adrenal oncocytoma and present a review of the literature particularly with regards to the radiological and histopathological features and their impact on the management.Adrenal oncocytomas are usually identified incidentally on imaging and can achieve large sizes. They should be considered in the differential diagnosis of any large upper abdominal lesion including those apparently arising from the liver as in this case report. MRI scan appears to be the ideal imaging modality to characterise such lesions. There seems to be little benefit in biopsying these masses and surgery remains the most optimal management. It remains difficult to predict metastatic behaviour based on histological findings and so long term surveillance is advisable. PMID- 22096672 TI - Adenoid cystic carcinoma of the base of the tongue: Late metastasis to the pancreas. AB - Adenoid cystic carcinoma (ACC) is a relatively rare epithelial tumor of the salivary glands. We present a 64-year-old gentleman with ACC of the tongue who following resection and radiotherapy, presented 10 years later with a lung metastasis and underwent operative intervention and further radiotherapy. Five years later he presented with obstructive jaundice found to be metastatic ACC. We believe this to be the first report of an ACC metastasizing to the pancreas. PMID- 22096673 TI - The sentinel placement of an open abdomen negative pressure unit. AB - The open abdomen is a common condition after a trauma necessitating celiotomy with the inability to close the fascia either due to damage control surgery or abdominal compartment syndrome. Traditionally the open abdomen has been approached with the use of the open abdomen temporary abdominal closure (Barker Vacuum Pack Dressing). More recently there has been the addition of the ABTheraTM open abdomen negative pressure unit introduced by KCI. Our case report is based on the first patient to have placement of the ABTheraTM device. PMID- 22096674 TI - Ovarian teratoma presenting as small bowel obstruction in an elderly lady-A case report. AB - Teratomas of the ovary are of the mature or immature type. The mature variety is called dermoid cysts, which is the most frequent benign germ cell tumour of the ovary in the reproductive age group. They are usually asymptomatic until they reach a significant dimension.(1) Pressure effect, torsion and rupture of an ovarian cyst may present as an acute abdomen. A case is presented where an elderly lady presented with small bowel obstruction due to a very large, non adherent to the intestine, dermoid cyst. PMID- 22096675 TI - Laparoscopic port site Richter's hernia - An important lesson learnt. AB - INTRODUCTION: We report a case of small bowel obstruction with strangulation caused by a port site hernia following a laparoscopic appendicectomy and the successful management of the problem by employing a laparoscopy assisted technique. The aim of this report is to emphasize the importance of fascial closures of trocar sites in order to significantly decrease postoperative morbidity. CASE REPORT: A 31 years old female presented with a classic clinical picture of acute appendicitis. She underwent an uneventful laparoscopic appendicectomy. A 12 mm trocar was used at the umbilical port. On Postoperative day three, the patient developed abdominal distension, crampy abdominal pain, nausea and bilious vomiting. Her white cell count increased to 16,500/mm(3), and CRP was 145. X-ray abdomen showed dilated small bowel with multiple air fluid levels. CT scan showed a herniated loop of small bowel into the trocar site with small bowel obstruction. Laparoscopy was done to confirm the Richter's hernia into trocar site with small bowel obstruction. The bowel loop could not be reduced laparoscopically. Limited exploration of the trocar site confirmed findings with necrosis of the antimesenteric portion of the small bowel. A limited bowel resection and anastomosis was performed. The patient had an uneventful recovery. CONCLUSION: Most port site hernias present within 10 days of the primary procedures, delayed hernias have been reported. CT scan is a helpful adjunct to differentiate port site hematoma from incarcerated small bowel. The knowledge of such a complication and its early diagnosis are important to avoid complications. PMID- 22096676 TI - Suspected oesophageal cancer in a 33 year old lady. AB - A previously healthy 33 year old lady presented with acute dysphagia with endoscopic and CT features of oesophageal carcinoma. Endoscopic ultrasound (EUS) revealed a large subcarinal lymph node compressing at the mid-oesophagus. Fine needle aspiration (FNA) showed a single well-formed epithelioid granuloma with no evidence of malignancy. Molecular analysis showed the aspirate to be positive for Mycobacterium tuberculosis. She continues to improve with standard anti-TB medication without surgery.This is a rare case of acute dysphagia secondary to primary tuberculous mediastinal lymphadenopathy. EUS and FNA have completely altered the clinical management of this lady. PMID- 22096677 TI - Endometriosis of the appendix: Report of three cases. AB - Endometriosis of the appendix is an entity of extragonadal endometriosis. It commonly affects women in the childbearing age with a wide spectrum of clinical manifestations. Women can present with symptoms mimicking acute appendicitis or chronic pelvic pain. The surgical management varies from simple appendectomy to right hemicolectomy depending on the clinical findings. We report 3 cases of endometriosis of the appendix presenting with appendiceal intussusception. The surgical literature is reviewed and current surgical management is discussed. PMID- 22096678 TI - Ileorectal fistula due to a rectal cancer-A case report. AB - A 51-year-old man was seen at our hospital because of diarrhea. Barium enema and colonoscopy revealed a cancer in the lower rectum and fistula formation from the site to ileum. Resection of the rectal cancer and ileorectal fistula was performed. Histologically, the resected lesion was mucinous adenocarcinoma with contiguous invasion from the rectum to the ileum. The patient is alive with no sign of recurrence 120 months after operation. Fistula formation between the colon and other gastrointestinal tract organs is very rare, especially for rectal cancer. Fistula-forming colorectal cancers are rarely found to have metastatic lesions in the liver, peritoneum and lymph nodes despite their invasive behavior; accordingly, curative resection involving partial resection of the intestine with fistula is expected. PMID- 22096679 TI - Clinical manifestation of RCC leptomeningealcarcinomatosis-A case study. AB - Whilst tumour spread to the meninges is not uncommon, occurring in up to 20% of various other tumours, leptomeningeal carcinoma from a primary renal cell carcinoma (RCC) is rare. To date, we are aware of only 3 other reported cases. We describe a 45-year-old man who underwent a radical nephrectomy for a large renal cell carcinoma of clear cell subtype. 1 month post nephrectomy, he was re admitted with vague neurological symptoms and was subsequently found to have malignant cells in his CSF. He deteriorated rapidly and was deceased within 10 days post admission. PMID- 22096680 TI - Intussusception of the appendix secondary to mucinous cystadenoma: A rare cause of abdominal pain. AB - A 35-year-old woman was seen as an outpatient with a 3-month history of pain in the right iliac fossa. A CT scan of her abdomen revealed the presence of a mucocele of the appendix. Intra-operatively, an appendico-appendicular intussusception was found. Histology confirmed the presence of a mucinous cystadenoma with the presence of acellular mucin on the serosal surface of the appendix. This association has rarely been described in the literature. Prompt surgical intervention is advocated to prevent the subsequent development of pseudomyxoma peritonei. We present a case of intussusception of the appendix with a mucinous cystadenoma as its lead point. PMID- 22096681 TI - Bilateral ovarian fibrothecoma. An uncommon cause of a large pelvic mass. AB - Ovarian fibrothecomas are uncommon tumors of gonadal stromal cell origin. They account for 3-4% of all ovarian tumors and in 90% of the cases are unilateral. Here, we describe a rare case of a bilateral ovarian fibrothecoma in a postmenopausal woman who presented with a large pelvic mass and metrorrhagia. Diagnostic evaluation and surgical management are discussed along with a brief review of the literature. Although rare, ovarian fibrothecoma should be considered in patients presenting with a large pelvic mass and postmenopausal bleeding. Radical surgery is the preferred management strategy for postmenopausal women with bilateral ovarian fibrothecomas and is associated with a good prognosis. PMID- 22096682 TI - Simple repair of a giant inguinoscrotal hernia. AB - We present a case of a giant inguinoscrotal hernia that extended almost to the patient's knees. Operative repair was through a standard transverse inguinal incision. No debulking or abdominal enlargement procedure had to be performed. The repair was done with a tension-free, onlay, prosthetic mesh repair. PMID- 22096683 TI - Spinal schwannomatosis in the absence of neurofibromatosis: A very rare condition. AB - Schwannomatosis is defined as an extremely rare tumors syndrome characterized by the presence of multiple schwannomas in the absence of typical signs of NF1 and NF2 syndromes. The genetic and molecular analysis performed on these tumors makes it possible to name schwannomatosis as distinct clinical and genetic syndrome. The treatment in the case of symptomatic lesions is surgical removal; if the lesions are asymptomatic it is better to perform serial MRI studies. Given the high incidence of developing additional lesions in patients with schwannomatosis, it remains imperative to perform serial brain and spinal cord MRI studies during follow-up. The differential diagnosis is important including clinical and radiological criteria plus molecular genetic analysis of tumor cells and lymphocyte DNA. We report a rare case of spinal schwannomatosis in which genetic analysis performed on surgical samples showed two different mutations in the cells of the two lesions. PMID- 22096684 TI - Colocutaneous fistula secondary to amoebiasis. AB - Here we present an interesting and extremely rare case of a 66 year old male who developed a colocutaneous fistula secondary to amoebiasis. The patient presented with an acute history of right lower abdominal pain, weight loss and a palpable mass. A CT scan demonstrated a fluid filled cavity in the right iliac fossa consistent with an appendiceal abscess which was drained under radiological guidance. However, following drainage his symptoms remained requiring open surgical drainage, and a controlled caecostomy was performed due to a small caecal perforation. Despite appropriate conservative therapy he failed to progress, and developed localised sepsis in the right iliac fossa with a colocutaneous fistula, requiring a formal right hemicolectomy. The histological examination confirmed the presence of abundant trophozoites of Entamoeba histolytica.We highlight the fact that in the modern age of immigration and long distance travel, it will become increasingly likely that the so-called 'tropical' diseases will present throughout the world. This case also highlights the need to keep an open mind in cases that do not progress as expected, and to react accordingly to any unusual developments. PMID- 22096685 TI - Sternum resection and reconstruction for metastatic renal cell cancer. AB - A 62-year-old male with bilateral renal cell carcinomas underwent bilateral nephrectomies. Following which he continued hemodialysis. He was admitted to our hospital with a small sternal mass present for 10 months. The operation consisted of sternectomy with right 4th costal cartilage resection and sternal reconstruction with Prolene mesh and methylmethacrylate. Postoperative course was uneventful and his respirations were normal without paradoxical movement of the thorax or hypoxemia. He is currently well and being followed up as an out patient. PMID- 22096686 TI - Platypnea orthodeoxia syndrome and bronchopleural fistula following right pneumonectomy: The first case of double misfortune following pneumonectomy. AB - We report a case of post-pneumonectomy right to left shunting via patent foramen ovale (PFO) and bronchopleural fistula (BPF). Although the latter complication is well-known following pneumonectomy, the former is quite rare. In terms of post pneumonectomy complications, no case has been reported, in which right to left shunting via PFO and BPF were synchronous. Low awareness of post-pneumonectomy PFO often results in delay of the appropriate management, like in our experience. The rarity and the complexity of our case as well as literature review of the post-pneumonectomy right to left shunting via PFO are summarized.With our case of post-pneumonectomy right to left shunting via PFO and BPF reviewed, we would like to show the rarity of our case and to enlighten all of the thoracic surgeons for early detection of this hemodynamic complication following pneumonectomy. PMID- 22096687 TI - An unusual groin exploration: De Garengeot's hernia. AB - De Garengeot's hernia is a rare surgical phenomenon and describes the presence of the vermiform appendix within a femoral hernia. We describe a case of acute appendicitis mimicking an irreducible femoral hernia and reiterate key operative techniques necessary to prevent post-operative morbidity associated with this pathology. PMID- 22096688 TI - Disconnected subduroperitoneal shunt catheter induces silent bowel perforation: An unusual complication. AB - We report a case of silent bowel perforation by a fractured subduroperitoneal shunt after surgical shunt revision. A 93-year-old bedridden man experienced transanal prolapse of a shunt catheter after defecation. Upon arrival, the patient showed no fever or acute abdominal signs. Abdominal computed tomography (CT) showed an abandoned shunt catheter in the lower abdomen with rectum perforation. The disconnected catheter was successfully removed from the anus by digital rectal maneuver, and no peritonitis or other complication developed afterward. Such broken shunts no longer provide drainage function, and also pose a risk of migrating into the hollow viscera. Therefore, even in the absence of overt peritoneal signs, disconnected catheters should be removed by laparoscopic or minimal surgery to prevent possible development of this unusual complication. Instances of the rare complication are reviewed, and pathogenesis and treatment of the condition are discussed. PMID- 22096689 TI - Arteriovenous malformation: An unusual cause of rectus sheath hematoma, following laparoscopic cholecystectomy. AB - Rectus sheath hematoma (RSH) is an accumulation of blood in the rectus abdominis muscle sheath, secondary to several conditions which may cause the epigastric vessel rupture or muscular tear, but mostly affecting patients undergoing anticoagulation therapy.We present a rare case of a 67-year-old woman who underwent laparoscopic cholecystectomy and developed RSH on the 12th postoperative day. The patient was under anticoagulation therapy with acenocoumarole due to mitral valve replacement. The bleeding source was an arteriovenous malformation (AVM) rupture as indicated by the angiogram images and it was embolized succefully. The patient was discharged seven days later. PMID- 22096690 TI - Case report of a symptomatic giant renal oncocytoma. AB - Renal oncocytomas are benign tumours, often asymptomatic, and picked incidentally on radiological imaging. We present a case report of a symptomatic giant renal oncocytoma in a 61-year old man having lower back/right flank pain. A large right renal mass was identified on abdominal CT scan. Radiological features were not sufficient to differentiate this lesion from renal cancer. Right radical nephrectomy was performed. Typical features of oncocytoma, without evidence of malignancy, were seen on histological examination of the specimen. In this report, we discuss literature review of radiological, genetic, and pathological characteristics of renal oncocytoma. PMID- 22096691 TI - Intramuscular cavernous haemangioma of the triceps. AB - Haemangiomas are one of the most common soft tissue tumours comprising 7% of all benign tumours. Vascular malformations are often confused with haemangiomas. The etiology is unknown. They are common in infancy and childhood and females are more commonly affected. These tumours may be superficial or deep, and deeply seated lesions, are difficult to diagnose clinically and hence require radiographic assessment. Deep-seated haemangiomas are usually intramuscular, although intra-articular synovial haemangiomas also occur. The commonest anatomic site is the lower limb.Despite their vascular origin, haemangiomas do not metastasize or undergo malignant transformation. Many treatment modalities for the symptomatic haemangioma are available but surgical excision is the preferred treatment. We present an unusual case of a dumb-bell intramuscular haemangioma involving the triceps and extending into the cubital tunnel of the elbow, distinguish between haemangiomas and vascular malformations and emphasize the importance of surgical technique in ensuring ulnar nerve safety. PMID- 22096692 TI - Sublingual-plunging ranula as a complication of supraomohyoid neck dissection. AB - Ranulas are rare cystic lesions resulting from damage or rupture of one or more of the ducts of the sublingual gland, that lead to mucus extravasation or dilatation of the gland's duct. Extravasation cysts are more common than retention cysts. We present a case of a 45-year-old male with a squamous cell carcinoma of the ventral surface of the tongue that was treated with excision of the oral lesion and bilateral supraomohyoid neck dissection without supplementary radiotherapy. A left myocutaneous platysma flap was raised for defect closure. Ten months postoperatively he presented complaining of swelling of the right submandibular region. The diagnosis, based on his medical anamnesis and the CT imaging, was a sublingual-plunging ranula. It is postulated that the ranula resulted from damage to the ducts of the sublingual gland during selective neck dissection. One year postoperatively there are no signs of recurrence either of the ranula or of the cancer. We suggest that sublingual gland excision and intraoral cyst marsupialization is a logical treatment for sublingual-plunging ranulas. PMID- 22096693 TI - Myofibroblastoma of the breast: Case report and literature review. AB - Myofibroblastoma of the breast is a rare benign mesenchymal tumor. The literature describes relatively few cases of this type of tumor. We report on a new case of myofibroblastoma in a 65-year old man successfully managed at our institution. The purpose of this case report is to highlight characteristics and differential diagnosis of this rare neoplasm. PMID- 22096694 TI - Metastatic hernial sac tumor in a patient with FUO. AB - The presence of primary or metastatic cancer within a hernia sac is uncommon, which occurs in fewer than 0.5% of all surgically excised sacs (1). This article demonstrates a case of a metastatic pancreatic cancer, one of which presented as an inguinal hernia with fever of unknown origin (FUO). A 44-year-old male presented with a history of FUO and a painful inguinal hernia. Inguinal canal exploration revealed a mass like lesion in the sac without any correlation to abdominopelvic viscera. Postoperative evaluations confirmed moderately differentiated metastatic adenocarcinoma from pancreatic origin. PMID- 22096695 TI - Ovarian hydatid cyst: A case report. AB - Discovering an hydatid cyst in pelvic region, especially as primary localization, is a rare event; as a matter of fact according to data provided by literature the incidence is between 0.2 and 2.25%. The ovarian involvement is often secondary to a cyst's dissemination localized in a different site. When possible the optimal treatment is represented by radical laparotomic cystectomy. We report a case of an old woman affected by this pathology that we have treated with a cyst's marsupialization after a draining and irrigation of cyst cavity with hypertonic saline solutions. PMID- 22096696 TI - A case of primary malignant fibrous histiocytoma of the duodenum. AB - BACKGROUND: Primary malignant fibrous histiocytoma (MFH) of the duodenum is rare and a distinct clinical entity. CASE REPORT: A 55-year-old man presented with a history of upper gastrointestinal bleeding, vomiting and decreased body weight over the past 2 months. Abdominal exam showed an epigastric mass of 10 cm. An upper gastrointestinal endoscopy documented a tumor in the third part of duodenum. The histopathological examination of biopsy has concluded a MFH. Abdominal CT revealed a large and heterogeneous mass of 10 cm in the third part of the duodenum. The intervention was conducted by way of a bi-subcostal laparotomy. Exploration of the tumor revealed involvement of the third part of duodenum. This lesion adhered and invaded the inferior vena cava. A palliative procedure using a gastro-entero-anastomosis was carried out with uneventful postoperative course. Neither adjuvant chemotherapy nor radiotherapy were conducted. The patient died four months following his operation. CONCLUSION: The biological behavior of malignat fibrous histiocytomas is extremely aggressive and mainly conditioned by size and histological grading. The treatment of choice, whenever possible, is based on early and complete surgical excision of the tumor. PMID- 22096697 TI - Bilateral DCIS following gynecomastia surgery. Role of nipple sparing mastectomy. A case report and review of literature. AB - Bilateral ductal carcinoma in situ of breast is a very rare disease in men. Ductal carcinoma in situ (DCIS) is an abnormal proliferation that involves the ductal epithelium and it has the potential of evolving into an invasive tumour. Gynaecomastia (female like breast in men) is a benign condition though it is associated with a reported 3% incidence of unilateral invasive breast cancer.(2) Synchronous bilateral breast cancer in association with gynaecomastia is exceptionally rare. The recommended treatment for DCIS in male is mastectomy. So far only 2 cases of bilateral DCIS in male patients has been reported in the literature treated with skin and nipple sparing mastectomies. We report another case of synchronous bilateral DCIS in a male treated with skin and nipple sparing mastectomies. A 44 year-old man with history of long-standing gynecomastia. He had no identifiable risk factor for the development of cancer. His pre operative assessment of breast including mammograms was normal. He underwent bilateral subcutaneous mastectomies, with subsequent incidental diagnosis of synchronous bilateral ductal carcinoma in situ. The case was discussed in multidisciplinary team meeting and the need for further surgery was felt including excision of nipple areola complex. However considering patient wishes, cosmetic outcome and recent literature it was decided to preserve nipple areola complex (NAC) with regular follow up evaluation. Our patient at completion of 18 months of treatment is doing well with no signs of local recurrence. PMID- 22096698 TI - A submucosal fecal mass as the complication of stapled hemorrhoidopexy: A case report. AB - Despite the early encouraging results and safety profile of hemorrhoidopexy, several serious complications have been reported including rectal perforation, retroperitoneal sepsis, pelvic sepsis and rectovaginal fistulas. The recent article is the report of the case of a 30 year old woman, with a submucosal mass which was palpable in the anterior rectum. She had undergone a stapled hemorrhoidopexy due to a 2nd degree internal prolapsed hemorrhoid three years previously. Operation was planned to identify the nature of the mass and a cylindrical impacted 4 cm * 2 cm fecal mass was excised. The recent finding seems to be the first one being reported in this issue. PMID- 22096699 TI - Malignant fibrous histiocytoma of rectum: Report of a case. AB - Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adults, mostly distributed in the thigh, buttock and groin (46%) and presents rarely in the gastrointestinal tract, classified as gastrointestinal stromal tumors (GIST). MFH is regarded as a diagnosis of exclusion, essentially synonymous with an undifferentiated pleomorphic sarcoma. The recent report presents an 80-year-old man with clinical manifestations of rectal bleeding and final diagnosis of MFH of rectum. It seems that radical resection and adjuvant radiation is important in the management strategy of a patient with such a rare rectal tumor. PMID- 22096700 TI - Gastrointestinal stromal tumor of the stomach in a child with a 3-year follow-up period-Case report. AB - We report a case of a nine-year-old boy with a 4-week history of general fatigue, loss of appetite, vomits and hematemesis. Laboratory evaluation revealed a hemoglobin level of 4.4 g/dl. After a transfusion of packed red blood cells the patient underwent an esophagogastroduodenoscopy, which showed a smooth, rounded 6 8 cm submucosal lesion with a central depression with ulceration and active bleeding in the cardia extending to the fundus.Computed tomography (CT) of the chest, abdomen and pelvis showed a large mass originating from the gastric wall but not infiltrating surrounding organs, approximately 8.0 cm * 7.0 cm * 5 cm. Despite the tumor size, no metastases were diagnosed. The patient underwent a total gastrectomy in an en-bloc resection including the distal part of the esophagus (3 cm) and omentum with oncologic margins. Reconstruction was performed with a mediastinal end-to-side esophago-jejunal anastomosis. Immunehistochemic confirmed GIST. He remains well without evidence of disease after 36 months of follow-up with a multiprofessional team. PMID- 22096701 TI - Ileocolic intussusception due to intestinal metastatic melanoma. Case report and review of the literature. AB - The small intestine is a frequent site of melanoma metastases and the most common cause of secondary intestinal tumors. Even though, its presentation with intestinal obstruction due to intussusception is very rare. We present a 47-year old woman with a medical history of facial melanoma operated 17 years ago and recently diagnosed of cervical recurrence who complained of abdominal pain of one week duration accompanied with vomiting and abdominal distension. Computed tomography (CT) scan revealed marked distension of the small intestine with features suggesting intussusception of the distal ileum. At laparoscopic exploration a massive ileocolic intussusception was found with invagination of the last 60 cm of ileum inside the cecum and ascending colon. Surgical reduction revealed a tumor of approximately 2 cm in the distal end of the intussuscepted intestine acting as the lead point. Resection of non-viable ileum along with the tumor and end-to-end anastomosis was performed. Many other lesions of smaller size were found distantly in the proximal small bowel but were not treated. The patient had a full recovery and was discharged three days after surgery. Pathological examination showed metastatic melanoma and a positron emission tomography (PET) scan confirmed disseminated disease with brain metastasis. The patient died three months after surgery. Intestinal occlusion due to metastatic disease is a rare condition but should be taken into account particularly in patients with history of cancer. Surgical intervention with a mini-invasive laparoscopic approach is feasible. Intestinal resection and anastomosis is mandatory for either curative or palliative intentions providing a satisfactory treatment. PMID- 22096702 TI - Primary hydatid cyst of pancreas with acute pancreatitis. AB - CONTEXT: Primary hydatid disease of the pancreas is very rare and even rarer to cause pancreatitis. CASE REPORT: We report the case of a 20-year-old man who presented with abdominal pain and an epigastric mass. A diagnosis of a pancreatic hydatid cyst was established by ultrasonography and CT scan before surgery. The treatment consisted of laparoscopic cyst evacuation with omentoplasty. The recovery was uneventful and the patient has remained symptom free so far. CONCLUSIONS: Hydatid disease should be considered in the differential diagnosis of all cystic masses in the pancreas, especially in the geographical regions where the disease is endemic. PMID- 22096703 TI - The use of minimally invasive surgery in the management of idiopathic omental torsion: The diagnostic and therapeutic role of laparoscopy. AB - Omental torsion is an unusual and infrequently encountered cause of acute abdominal pain in adults. Computed tomography (CT) is a useful adjunct to clinical history and examination in establishing the diagnosis; however, definitive diagnosis is frequently established at the time of exploratory surgery. Treatment may be conservative or operative, with laparoscopic resection the surgical approach of choice. We report the case of a 60-year-old man who presented with a 3-day history of severe right-sided abdominal pain. Abdominal CT scan revealed a right upper quadrant mass with a whirl-like appearance, suspicious for omental infarction. Diagnostic laparoscopy was undertaken, the diagnosis confirmed and the diseased omentum resected. The patient was discharged the following day and made an uncomplicated recovery. PMID- 22096704 TI - Intrapancreatic accessory spleen: A case report and review of the literature. AB - We present the case of a 26 year old male who was found to have a mass in the tail of the pancreas on an ultrasound scan. The lesion was suspicious for a non functioning pancreatic neuroendocrine tumour (PNET) and so he underwent distal pancreatectomy. Pathology revealed this to be an intrapancreatic accessory spleen (IPAS). This is a rare entity, and the literature on this subject is reviewed. A lesion in the pancreas that enhances in a manner similar to the spleen, whether the contrast is used in the setting of a Contrast Enhanced Ultrasound, a contrast enhanced CT scan, or a gadolinium enhanced MRI scan, is suggestive of IPAS. Nonetheless, the majority of these rare lesions are likely to be surgically excised rather than observed due to the similar appearance to PNET. PMID- 22096705 TI - Use of omental pedicles in mycotic abdominal aortic aneurysm repair. AB - We report a case of a sixty year old man with a mycotic infra-renal abdominal aortic aneurysm complicated by a left psoas abscess. After treatment with parenteral antibiotics he underwent early aortic reconstruction with an in-situ prosthetic graft wrapped in an omental pedicle. Mycotic abdominal aortic aneurysms can be treated in this way despite the potential for graft infection from persisting retroperitoneal sepsis. PMID- 22096706 TI - Malignant fibrous histiocytoma of the mandible and the infratemporal fossa-A case report. AB - Malignant fibrous histiocytoma is a sarcoma which commonly occurs in the soft tissues, joints and tendons of the extremities of adults but its occurrence in the oral and maxillofacial region is very rare. We present a rare case of malignant fibrous histiocytoma of the mandible with recurrence in the infratemporal fossa after surgery and radiotherapy. Patient underwent second surgery and complete tumor excision with minimal loss of function was achieved. Patient survived 8 years after surgery and died of natural cause. PMID- 22096707 TI - Diagnosis and management of idiopathic omental infarction: A case report. AB - A 32 year old man presented to casualty on three occasions in the space of four days, with intermittent, worsening abdominal pain. These symptoms imitated other commoner causes of acute abdomen and the site of onset changed, both factors delaying diagnosis. In due course, computer tomography imaging established findings indicative of omental infarction. Patient was discharged from hospital nine days later, having made a satisfactory recovery following successful conservative treatment. In this report, we evaluate the merits of a similar approach in future instances. PMID- 22096708 TI - Petersen's space hernia: A rare but expanding diagnosis. AB - BACKGROUND: Petersen's space hernia is caused by the herniation of intestinal loops through the defect between the small bowel limbs, the transverse mesocolon and the retroperitoneum, after any type of gastrojejunostomy. The laparoscopic approach facilitates the occurrence of this type of hernia, due to the lack of post-operative adhesions which prevent bowel motility and hence, herniation. CASE REPORT: We report the case of a 46 year-old male submitted to an open antrectomy and vagotomy with a Roux-en-Y reconstruction six-years before, for the treatment of bleeding gastric ulcer.He presented with epigastric abdominal pain radiating to the back and alimentary vomiting with a 3 days evolution, with an episode of hematemesis 2 h before admission. His abdomen was bloated and tender at the epigastric region. The laboratory exams revealed mild leucocytosis and CRP elevation with normal pancreatic tests. The abdominal CT scan revealed an intestinal occlusion. An exploratory laparotomy was performed, disclosing an incarcerated Petersen space hernia of the common limb, with obstruction and dilatation of the biliary limb. CONCLUSION: The knowledge of this anatomic post operative defect and a low threshold for diagnosis are crucial to its management, since its nonspecific clinical and laboratory findings. Early operative intervention is warranted in order to avoid the severe complications of bowel necrosis. PMID- 22096709 TI - Infection of an esophageal cyst following endoscopic fine-needle aspiration. AB - In this report, we describe an unusual presentation of an esophageal cyst. Esophageal cysts are generally benign and are frequently asymptomatic until progressive enlargement leads to symptoms of obstruction. Incidental discovery usually warrants excision. In the described case, a patient presented with signs of enlargement and concerns for infection after an attempted endoscopic biopsy of the lesion. After admission and initial management with antibiotics she was taken to the operating room for resection via a thoracotomy. We review the literature and underscore the conventional practice of operative management of esophageal cysts without the use of invasive diagnostic evaluations. PMID- 22096710 TI - Platypnea-orthodeoxia due to fat embolism. AB - Platypnea-orthodeoxia is an uncommon syndrome that is characterized by dyspnea relieved by recumbency and deoxygenation following a change from a recumbent to an upright posture. We herein describe a case of platypnea-orthodeoxia in a 75 year-old man after a surgical restoration of a bitrochanteric fracture of his right femur. However, in this extremely rare case, none of the current known anatomical or functional conditions which can cause platypnea-orthodeoxia had been diagnosed. We strongly believe that this syndrome could be also the result of fat embolism. PMID- 22096711 TI - Perineal scar endometriosis ten years after Miles' procedure for rectal cancer: Case report and review of the literature. AB - Endometriosis within a perineal scar after a Miles' procedure has not been previously reported in literature. We report a case of a 35-year-old-female who was treated 10 years before at the same institution for a low rectal cancer that presents with two discrete subcutaneous bulges within her perineal wound. Since the patient was asymptomatic and the complete work up for recurrent disease showed no evidence of malignancy, first line therapy was conservative. After two pregnancies and a caesarean section, the patient presented at our observation with enlarged and tender perineal nodules. The patient was treated with a wide excision of the perineal scar en-bloc with the nodules. Final pathology report was consistent with scar endometriosis. PMID- 22096712 TI - Dieulafoy lesion endoscopically rubber banded, with further severe haematemesis requiring emergency laparotomy - Case report. AB - Dieulafoy lesion is a rare cause of massive gastrointestinal haemorrhage that can be fatal. We report a case of a sixty-year-old lady who presented to the emergency department with haematemesis and melaena. During oesophagogastroduodenoscopy (OGD), an active bleeding vessel was seen on the lesser curvature of the stomach, near the gastro-oesophageal junction and a diagnosis of Dieulafoy's lesion made. The lesion was managed with the application of two rubber bands. Our patient re-presented to the emergency department ten days later with severe haematemesis requiring an emergency laparotomy.A search of the entire English literature using PubMed with the phrase 'Dieulafoy' has been performed. Papers were reviewed in relation to management of this lesion with rubber banding via endoscopy. The current available haemostatic methods are described. PMID- 22096713 TI - Is laparoscopic cholecystectomy safe for acute cholecystitis in the presence of ventriculo-peritoneal shunt? AB - INTRODUCTION: In patients with ventriculo-peritoneal shunts, laparoscopic procedures were previously contraindicated for the potential risks of elevating intra-cranial pressure resulting from increased intra-abdominal pressure and shunt malfunction/infection. PRESENTATION OF CASE: Here we present a case of a patient with ventriculo-peritoneal shunt who successfully and uneventfully underwent laparoscopic cholecystectomy for acute cholecystitis without any shunt manipulation or intra-cranial pressure monitoring. DISCUSSION: Several methods have been suggested to decrease the risks of increased intra-cranial pressure during laparoscopic cholecystectomy in patients with ventriculo-peritoneal shunts, but have not been routinely used. CONCLUSION: Standard technique laparoscopic cholecystectomy can be safely used to manage patients with VP shunts presenting with acute gall bladder disease. PMID- 22096714 TI - Traumatic mesenteric cyst after blunt abdominal trauma. AB - Mesenteric cysts are rare abdominal tumors of unclear histologic origin, usually asymptomatic. Post-traumatic mesenteric cyst usually results as a consequence of a mesenteric lymphangitic rupture or a hematoma followed by absorption and cystic degeneration. The preoperative histological and radiological diagnosis is difficult. We present the case of a 45-year-old male patient with sizable, palpable abdominal tumor, the gradual swelling of which the patient himself combined with the blunt abdominal trauma he acquired from an opponent's knee in a football game 5 months ago. PMID- 22096715 TI - Idiopathic spontaneous haemoperitoneum due to a ruptured middle colic artery aneurysm. AB - INTRODUCTION: Idiopathic spontaneous intra-abdominal haemorrhage is a rare, but challenging condition, associated with high mortality if not managed appropriately. The preoperative diagnosis is difficult, despite the recent advances in imaging. We present the clinical manifestations of this condition, as well as the available diagnostic and therapeutic modalities. PRESENTATION OF CASE: We report a case of a spontaneously ruptured dissecting aneurysm of the middle colic artery, which was managed with an emergency laparotomy and aneurysmatectomy. Interestingly, no evidence of vasculitis, infection or collagen disease was discovered during the histopathology examination of the specimen. DISCUSSION: The treatment of idiopathic spontaneous intra-abdominal haemorrhage revolves around patient resuscitation and management of the source of bleeding. In case of a ruptured aneurysm of the middle colic artery, the surgical management includes emergency laparotomy, arterial ligation and resection of the aneurysm. Transarterial embolisation has been suggested as a safe and less invasive alternative approach. CONCLUSION: A ruptured middle colic artery aneurysm should be included in the differential diagnosis of any unexplained intra-abdominal haemorrhage. Aneurysmatectomy is the treatment of choice, with radiologic interventional techniques gaining ground in the management of this entity. PMID- 22096716 TI - Spontaneous biliary peritonitis, or delayed bile leak? AB - INTRODUCTION: Spontaneous biliary peritonitis is a rare cause of acute abdominal pain. Whilst usually of extrahepatic origin, here we describe an even rarer perforation of an intrahepatic duct. PRESENTATION OF CASE: A 31 year old woman presented with acute onset epigastric abdominal pain on a background of cholecystectomy four years prior. Laparoscopy demonstrated bilious fluid but failed to identify the site of bile leak. Subsequent ERCP localised the leak to an anomalous radical of the right hepatic duct. DISCUSSION: Spontaneous biliary peritonitis is a rare diagnosis. Most cases are extrahepatic and the pathogenesis of intrahepatic ductal rupture has been difficult to define. Whilst acute bile leak is a recognised complication of cholecystectomy, bile leak four years following operation has not been described previously. CONCLUSION: Spontaneous biliary peritonitis remains as a rare cause of acute abdominal pain. Within the context of cholecystectomy, the surgeon should always be alert to the possibility of delayed bile leak. PMID- 22096717 TI - Utility of preoperative visualization for intrapulmonary sequestration in video assisted thoracoscopic surgery. AB - We herein report the case of a 59-year-old male suffering from severe cough. The patient had previously experienced several episodes of pneumonia beginning in childhood. A three dimensional multidetector computed tomography (3D-MDCT) scan revealed pulmonary sequestration with a left gastric artery blood supply, and clearly revealed the other pulmonary vessels. The patient underwent video assisted thoracoscopic surgery, in which the anomalous tissue was resected safely. Preoperative visualization of the vessels may be helpful for the safe treatment of a pulmonary sequestration, and the VATS approach is a suitable operation under corrective surgical planning. PMID- 22096718 TI - Transabdominal laparoscopic adrenalectomy of a large adrenal lipoma: A case report and review of literature. AB - The exponential increase in use of computer tomography (CT) and magnetic resonance imaging (MRI) has lead to a significant increase in the detection of asymptomatic adrenal masses. The prevalence of adrenal "incidentalomas" is approximately 4-10%. We present a case of a 55-year-old male with a large right adrenal mass that was followed by serial computer tomography scans and multiple non-diagnostic core biopsies. Due to the large size of the mass and unknown pathology, the patient underwent laparoscopic adrenalectomy. The patient's post operative course was uneventful. Pathology revealed a very unusual finding, a large adrenal lipoma. Adrenal lipomas are rare, benign, non-functioning tumor like lesions that occur with a relative frequency of only 0-11%. Over the past decade approximately 10 cases have been reported in literature. We review the literature of the current diagnostic and surgical treatment of adrenal lipomas (Pubmed and Cochrane from 1992-current). PMID- 22096719 TI - Bilateral symmetrical periprosthetic (mirror) fractures of knee fixed with dual plating technique. AB - INTRODUCTION: Periprosthetic fracture following total knee arthroplasty is a potentially serious condition. Here we report a case of bilaterally symmetrical (mirror) fracture of supracondylar area following trivial trauma. PRESENTATION OF CASE: Both fractures were OTA 33A2 and according to Rorabeck classification they were type II. Both fractures were fixed by dual plating technique using non locking plates. Intra operative fracture site biopsy revealed marked osteopenia and hence the patient was treated for osteoporosis. DISCUSSION: Both fractures united well at 14 weeks. At final follow up of 6 years there were no radiological signs of implant loosening and the patient was able to walk without any aids and had a range of 80 degrees and 60 degrees flexion in the right and left knees respectively. CONCLUSION: We conclude that in the pre locking plate's era such difficult case has been successfully managed by dual plating technique. PMID- 22096720 TI - Inferior epigastric artery false aneurysm following incisional hernia repair. AB - INTRODUCTION: We report a case of IEA false aneurysm following a mesh repair of a large incisional hernia. We emphasize the importance to consider the diagnosis to help avoid inappropriate interventions which could increase patient morbidity. CASE REPORT: A 68-year-old male patient, who 4 weeks previously had had a mesh repair of a large incisional hernia, presented with a painful left iliac fossa swelling. This was found to be an IEA false aneurysm. This was treated successfully with percutaneous thrombin injection. CONCLUSIONS: We feel an inferior epigastric artery false aneurysm must be included in the differential diagnosis when investigating the cause of any lateral swelling following incisional hernia repair. This would help reduce the chance of a missed diagnosis and avoid any inappropriate interventions which may cause increased patient morbidity. PMID- 22096721 TI - Sigmoid endometriosis and a diagnostic dilemma - A case report and literature review. AB - INTRODUCTION: Intestinal endometriosis is often an infrequently considered diagnosis in female of childbearing age by general surgeon. There is a delay in diagnosis because of constellation of symptoms and lack of specific diagnostic modalities. Patients suffer from intestinal endometriosis for many years before they are diagnosed. Often, such patients are labelled with irritable bowel syndrome. Intestinal endometriosis has a diagnostic time delay of 8-11 years due to its non-specific clinical features and multi-system involvement. PRESENTATION OF CASE: Our patient was a 32 years old Caucasian female who was referred to us with features of intestinal obstruction. Despite repeated clinical assessments and use of different diagnostic modalities the diagnosis was still inconclusive even after 21 days of her first presentation to primary care physician. She had an exploratory laparotomy, sigmoid colectomy, and Hartmann's procedure with a temporary colostomy with us. Histopathology confirmed endometriosis and also showed melanosis coli. She was referred to the gynaecological team for review and follow up. DISCUSSION: Intestinal endometriosis should be considered as a differential diagnosis in female patients of childbearing age group presenting with non-specific gastrointestinal signs and symptoms. Our patient manifested intestinal endometriosis and melanosis coli on histopathology suggesting symptoms of long duration. CONCLUSION: Bowel endometriosis is a less considered and often ignored differential diagnosis in acute and chronic abdomen. This condition has considerable effect on patient's health both physically and psychologically. PMID- 22096722 TI - A rare case of segmental small bowel pneumatosis intestinalis: A case report. AB - INTRODUCTION: Pneumatosis intestinalis is a rare condition affecting 0.03% of the population. It has a myriad of aetiological causes and hence presentation can vary immensely. The management of symptomatic pneumatosis intestinalis in an acute and outpatient setting remains a challenge to both physicians and surgeons. CASE PRESENTATION: We present a case of a 79 year old who presented in a gastroenterology outpatients department with a history suggestive of intermittent small bowel obstruction associated with abdominal pain aggravated by eating and posture. He was found to have signs suggestive of Marfan's syndrome. Computed tomography demonstrated extensive pneumatosis intestinalis of the small bowel. Due to deterioration in symptoms, an exploratory laparotomy was performed demonstrating segmental small bowel pneumatosis intestinalis secondary to a hypermobile mesentery. CONCLUSION: This case highlights the importance of both surgical and gastroenterology expertise in successfully managing symptomatic pneumatosis intestinalis. PMID- 22096723 TI - Post-biopsy renal allograft compartment syndrome: Addressing the problem, illustrated with a case report. AB - INTRODUCTION: Renal allograft compartment syndrome (RACS) has recently been coined to describe early allograft dysfunction secondary to raised pressure in the retroperitoneal space. This may be caused by direct compression of the renal vessels or by a diffuse renal parenchymal compression. Herein, we report a renal allograft compartment syndrome secondary to a needle core transplant biopsy and discuss the management strategies in line with an updated literature review. PRESENTATION OF CASE: A retrospective case-note review was carried out where a 45 year-old male had a transplant renal biopsy at 4-weeks after transplant for raising creatinine. Following biopsy patient developed abdominal discomfort and had haematuria. DISCUSSION: Doppler ultrasound scanning of graft demonstrated good perfusion but a small haematoma (2 * 2 * 2 cm) in the upper pole of the kidney at the site of the biopsy. Patient was thereafter assessed conservatively with serial ultrasound monitoring. After 24 h, significant deterioration of graft function was observed. The third scan, demonstrated reversed flow in diastole in the upper pole of the kidney with a resistive index of 1.0 in the main renal vessel. With the above findings the kidney transplant was explored immediately and the transplant released from a 300 ml of liquefied haematoma, which was under considerable pressure. In the next 24-h, the patient showed an immediate return of graft function. CONCLUSION: We recommend sequential ultrasound Doppler scanning as an invaluable tool to help identify early RACS. The surgical exploration and adequate heamostasis with surgical glue should be sought out in all RACS. PMID- 22096724 TI - Giant celiac artery aneurysm: Treatment by transcatheter coil embolization. AB - Celiac artery aneurysms (CAA) are one of the rarest forms of visceral artery aneurysms. Most patients are a symptomatic at the time of diagnosis and aneurysms are detected incidentally during diagnostic imaging for other diseases. We present the case of a 42-year-old man who had an asymptomatic giant CAA detected incidentally by an abdominal ultrasound investigating an abdominal pain. A contrast enhanced computed tomography angiogram (CTA) revealed a large CAA measuring 7.1 cm * 4.3 cm with extensive collaterals from the superior mesenteric artery (SMA). The aneurysm sac was mostly filled with thrombus with the celiac artery branches occluded. Pre-procedural angiography and transcatheter embolization procedures were performed at the same session. Endovascular exclusion was performed by transcatheter coil embolization and packing of the aneurysm sack. Technical success was achieved by the absence of flow in the aneurysm, and preservation of the native circulation on angiograms obtained just after the transcatheter coil embolization procedure. One week postembolization, a CTA confirmed thrombosis of the aneurysm. The patient returned for a follow-up CTA 3, 6, 12 and 48 months after embolization. The aneurysm was thrombosed and the patient remained a symptomatic. The surgical mode of treatment of CAA is increasingly being replaced by endovascular embolization because of the lower morbidity and mortality and high success rate. The accepted endovascular approach is by coil embolization of the aneurysmal lumen, the proximal and distal aneurysmal neck, or both. PMID- 22096725 TI - Primary squamous cell carcinoma of breast with ipsilateral axillary lymph node metastasis: An unusual case. AB - INTRODUCTION: Pure squamous cell carcinoma of the breast [SCCB] is rare. PRESENTATION OF CASE: We report a case of primary squamous cell carcinoma of breast with ipsilateral axillary lymph node metastasis in a 58year old woman. DISCUSSION: It is a breast carcinoma entirely composed of metaplastic squamous cells that may be keratinized, non-keratinized or spindled. The pure squamous cell carcinoma usually present with central cystic cavity, which we found in our case, also supported by immunohistochemical evidence. CONCLUSION: Although a rare breast cancer subtype, SCCB is of considerable interest due to its pathological heterogeneity and differences in clinical behavior and less reported occurrence of nodal metastasis. PMID- 22096726 TI - Inguinal herniae: Valuable clues to concurrent abdominal pathology: A series of case studies describing unusual findings in 'routine' hernia operations which demonstrate the need for thorough surgical training. AB - INTRODUCTION: The case series presented here demonstrates that the pathology encountered during inguinal hernia repair can often provide clues to concurrent pathology; the well trained surgeon's broader medical knowledge can lead to earlier diagnosis. PRESENTATION OF CASES: The case series examines four cases of men presenting with inguinal hernias, who were found to have concurrent abdominal pathology after further investigation of the intraoperative findings of the surgeon. DISCUSSION: Operating surgeons not only require the necessary surgical skills to deal with the unexpected, but must also rely on their ability to think laterally when interpreting atypical incidental findings during 'routine' procedures. CONCLUSION: Experience and knowledge gained through a surgeon's career is essential to enable them to correctly interpret their intraoperative findings and potentially diagnose concurrent pathology. The authors believe that surgical care practitioners, trained in just 2 years, would lack these essential skills. PMID- 22096727 TI - Facial infiltrating lipomatosis: A case report and review of literature. AB - Infiltrating lipomatosis of the face has been described as a congenital disorder in which mature lipocytes invade adjacent tissues in the facial region. The presentation is always unilateral with hypertrophy of hard and soft structures on the affected side of the face. We present a case of a 27-year-old female who reported with a complaint of recurrent unilateral facial swelling with history of two previous resections, the histopathology or details of these surgeries were not available. The patient underwent resection of tumour and the histopathology confirmed it to be infiltrating lipomatosis. The surgery resulted in a definite improvement in the facial asymmetry and the patient is being closely followed up with no evidence of recurrence. The pathogenesis of the condition is unclear, though it has been postulated that the condition is at one end of a spectrum of overgrowth syndromes with classic Proteus syndrome on the other extreme. Management of this condition involves resection of the tumour which in most cases is subtotal to reduce the risk of damage to facial nerve. There is a controversy regarding both timing and extent of resection in the literature and we think the subtotal resection of tumour in an adolescent or older patient can give good aesthetic outcome without compromising facial nerve function. However, the patients should be informed about high rate of recurrence and increase risk of complications with any subsequent surgery. PMID- 22096728 TI - Long term survival after right hemicolectomy and pancreatoduodenectomy for locally advanced colonic cancer: Case report. AB - Locally advanced colorectal tumors represent about 5-22% of all colorectal cancers at the time of presentation. Specifically in the case of right colon cancer, the percentage of adjacent structure involvement ranges between 11% and 28%. Organs that are most frequently invaded by right colonic tumors are the duodenum and the pancreatic head. We report the case of a 36-year old man with locally advanced right colonic cancer, invading the head of the pancreas and the superior mesenteric vein, who was successfully treated in our department with right hemicolectomy, pancreatoduodenectomy and short resection of the superior mesenteric vein with an end-to-end anastomosis, and remains alive and well, free of disease, nine years after the operation. PMID- 22096729 TI - Bilateral recurrent wrist flexor tenosynovitis and rice body formation in a patient with sero-negative rheumatoid arthritis: A case report and review of literature. AB - INTRODUCTION: Rice body formation has been traditionally observed in the joint and tendon sheaths of patients with tuberculosis. Few case reports exist that describe rice body formation in patients with rheumatoid arthritis. We describe a case report of bilateral recurrent wrist flexor tenosynovitis with rice body formation in a patient with sero-negative rheumatoid arthritis. PRESENTATION OF CASE: This case report describes a 72 year old lady presenting with severe bilateral, flexor tenosynovitis of the wrists. Ultrasonography revealed significant echogenic fluid on the palmer aspect of wrist joint surrounding flexor tendons with intact neurovascular bundles and no bony erosion. Laboratory tests demonstrated elevated erythrocyte sedimentation rate (50 mm/h) and negative rheumatoid factor. A sequential subtotal flexor tenosynovectomy was carried out with decompression of the carpal tunnel. During the operation, multiple rice bodies among the flexor tendons with adherent synovitis were found. Histology revealed disrupted synovial tissue containing several areas of fibrinoid necrosis, bounded by a layer of vaguely pallisaded histiocytes but no epitheloid granulomata or germinal centre. A revision surgery with debulking of the fibro osseous canal was undertaken following recurrence. The patient presently has complete resolution of symptoms at one year follow-up. DISCUSSION: The combined clinical, laboratory, ultrasound and histology findings of the patient indicated that the cause of the rice body formation was due to a sero-negative arthritis rather than tuberculosis. CONCLUSION: Rice body formation can be caused by sero negative arthritis. Bilateral wrist flexor tensosynovitis can recur within five months of a previous synovectomy in a patient with sero-negative arthritis. PMID- 22096730 TI - Incarcerated spontaneous transdiaphragmatic intercostal hernia. AB - INTRODUCTION: Prolapse of abdominal viscera into the thoracic subcutis through the chest wall is known as transdiaphragmatic intercostal hernia (TIH). Herein, we present the first case of spontaneous TIH presenting as a thoracoabdominal emergency. PRESENTATION OF CASE: A 78-year-old male presented with acute left thoracoabdominal pain following a sudden bulge at the left posterolateral chest wall corresponding to a partially reducible soft tissue mass with ecchymosis at the overlying skin. Paroxysmal cough during the last four days was also reported along with a prolonged daily application of a special tight abdominal belt that used while milking sheep. CT-scan of the abdomen showed intrathoracic proptosis of the splenic flexure through a defect of the left hemidiaphragm and subcutaneous prolapse of the herniated colon through the 7th intercostal space. On laparotomy, the herniated colon showed signs of ischemic necrosis leading to segmental colectomy followed by repair of the diaphragmatic defect. DISCUSSION: The clinical diagnosis of spontaneous TIH demands very high index of suspicion and thorough patient's history. In this case the daily elevation of the intraabdominal pressure due to an abdominal milking belt might have caused gradual slimming and loosening of the diaphragm and the intercostals muscles rendering them vulnerable to sudden increases of the thoracoabdominal pressure due to violent coughing. Such a hypothesis is reasonable in the absence of traumatic injury in this patient. CONCLUSION: Spontaneous TIH should be suspected in patients presenting with a sudden palpable chest wall bulge and associated thoracoabdominal symptoms in the absence of preceding injury. PMID- 22096731 TI - A perforated diverticulum in Cushing's disease. AB - We report a case of perforated colonic diverticulum in Cushing's disease. Although perforated diverticuli have been described in patients with Cushing's syndrome secondary to exogenous glucocorticoids, this complication has not been described in patients with Cushing's disease. Patients with hypercortisolism, from either exogenous or endogenous sources, should be monitored for diverticular perforation. PMID- 22096732 TI - Small bowel perforation secondary to accidental dental plate ingestion. AB - The majority of ingested foreign bodies will pass through the gastrointestinal tract without incident, with less than 1% of cases resulting in complications. Herein we present a case of small bowel perforation secondary to the accidental ingestion of a dental plate. A diagnosis of perforation was made by CT imaging, but the exact cause could only be determined after resection of the affected bowel and histo-pathological examination. We re-iterate the importance of accurate and thorough history taking in patients with possible foreign body ingestion. PMID- 22096733 TI - The adverse consequences of pyoderma gangrenosum in a 13 year old child. AB - INTRODUCTION: Pyoderma gangrenosum (PG) is an uncommon, but serious, non infectious, neutrophilic dermatosis that causes cutaneous necrosis with a characteristically rapid evolution. PRESENTATION OF CASE: A 13 year-old girl was admitted with a postoperative infected wound, which was surgically debrided. A new more aggressive lesion on the left upper extremity led the patient to the intensive care unit. Clinical diagnosis of pyoderma gangrenosum was introduced with a crucial delay. An immediate clinical improvement after immunosuppressive therapy with systemic corticosteroids and cyclosporine was observed. The extensive cutaneous deficits were covered with keratinocyte cultured cells with an aesthetically good outcome. DISCUSSION: Diagnosis of PG in young children is very difficult, especially without dermatological evaluation. This deforming ulcerative skin disease is probably a result of altered immunologic reactivity. Its early recognition may prevent unnecessary surgical treatment which leads to dangerous complications. CONCLUSION: To our knowledge this is the first case of PG with such a widespread distribution reported in a child, as a consequence of iatrogenic pathergy. PMID- 22096734 TI - Colon cancer presenting with polymyositis-A case report. AB - INTRODUCTION: Colorectal cancer most often presents with a change in bowel habit, weight loss or with bleeding per rectum. Much less commonly, colorectal cancer may present as part of a paraneoplastic syndrome. Polymyositis is a rare disease most often considered a complement-mediated idiopathic inflammatory myopathy manifested by proximal muscle weakness. However, polymyositis may also be part of a paraneoplastic syndrome associated with an underlying malignancy. The relationship between polymyositis and malignancy is well known, but it has been suggested that tumours of the large bowel are rarely complicated by myositis. PRESENTATION OF CASE: The authors describe a case report of an 82-year-old gentleman with a presumed musculoskeletal or neurological deficit who was subsequently diagnosed with metastatic colon cancer in the setting of progressive fatigue and muscle weakness. Concurrently, we review the current literature looking at the relationship between cancer and polymyositis. DISCUSSION: Colorectal cancer rarely presents with symptoms such as muscle weakness, however it is important to be aware of the possibility of an underlying malignancy when seeing patients with symptoms which are suggestive of polymyositis. CONCLUSION: The diagnosis of polymyositis in the elderly population should raise suspicion of an underlying malignancy. PMID- 22096736 TI - Massive per rectal bleeding following blunt abdominal trauma: First presentation of Crohn's disease. AB - INTRODUCTION: Inflammatory bowel disease is a chronic and relatively common disorder with heterogeneous presentation. Peak incidence occurs in the second and third decades of life. We present a patient with Crohn's disease whose first presentation was profuse bleeding/rectum following blunt abdominal trauma. PRESENTATION OF CASE: A 29 year old previously healthy man presented one hour after sustaining relatively mild abdominal trauma, due to fall onto the ball during a rugby match. He complained of abdominal pain and one episode of large fresh rectal bleeding. He was pale and distressed with hypotension, tachycardia and abdominal guarding & fresh blood on digital rectal examination. With a provisional diagnosis of intestinal injury he was taken to theatre. Right hemi colectomy was done for a thickened and inflamed segment of distal ileum, a large adjacent mesenteric haematoma & mesenteric lymph nodes and blood in distal bowel. Histology confirmed the features of Crohn's disease. DISCUSSION: Crohn's disease is unusual cause of massive lower gastrointestinal bleeding occurring in 0.9-6% of patients. Rectal bleeding associated with diarrhoea is relatively more common than massive bleeding. The presence of Crohn's disease in young patients presenting like this is unlikely to be suspected and diagnosis could only be made after laparotomy. PMID- 22096735 TI - Giant gallstone: A case report. AB - INTRODUCTION: There is a high incidence of gallstones in the Chilean population. PRESENTATION OF CASE: We report on a 57-year-old man who complained of abdominal pain in the right upper quadrant. Abdominal ultrasound indicated acute cholecystitis and a single, extremely large pear-shaped gallstone (16.8 cm long, and 7.8 cm at its widest point and 4.1 cm at its narrowest point). Its fresh weight (at operation) was 278.0 g and, after 4 years, its dry weight was 259.5 g. Emergency classical cholecystectomy was carried out successfully. DISCUSSION AND CONCLUSION: We have been unable to find a report of a larger gallstone in the English or Spanish language medical literature. PMID- 22096737 TI - A giant adrenal cyst difficult to diagnose except by surgery. AB - INTRODUCTION: Adrenal cysts represent rare clinical entities. Although surgical indications are well defined, pitfalls arise from the failure to establish an accurate preoperative diagnosis. Cystic lesions of other abdominal organs especially the pancreas complicate the diagnostic field. PRESENTATION OF CASE: We present the case of a giant adrenal cyst in a young female causing diagnostic dilemma. Imaging studies revealed a large cystic lesion of uncertain origin located between the spleen and the tail of the pancreas. It was decided to perform a laparotomy which confirmed the presence of an adrenal cyst and enucleation of the cyst was performed. Examination at one year confirmed no complications. DISCUSSION: Adrenal cysts should always be included in the differential diagnosis of cystic abdominal lesions. CONCLUSION: When the preoperative diagnosis is uncertain, surgical intervention can be both diagnostic and therapeutic. PMID- 22096738 TI - Unilateral borderzone infarction in a young polytrauma patient. AB - Although post-traumatic cerebral infarction is a known complication of craniocerebral trauma, borderzone infarction (BZI) after multiple traumas in young adults are uncommon and published data on this are extremely scant. We present an unusual occurrence of unilateral borderzone infarction in a 21-year old male who sustained multiple traumas in a traffic accident, which included mild head injury, blunt cardiac injury, right traumatic hemopneumothorax, and three long bone open fractures. Initial head scan revealed mild brain edema, and the BZI was uncovered by a repeated brain CT scan since the patient had a delayed neurological deficit which was incompatible for the injury severity of the head. Comprehensive work-up was performed and a narrowed right internal carotid artery was disclosed by CT angiography. Although unilateral BZI is extremely rare in young patients, emergency physicians should still keep in mind to warrant serial examinations for BZI and early recognition to provide appropriate treatment. PMID- 22096739 TI - Primary malignant melanoma presenting as superior mediastinal mass. AB - Malignant melanoma accounts for 1.5% of all cancers, and arises from a preexisting nevus in 40% of cases. Skin is the most common site for primary malignant melanoma. We present an extremely rare case of primary malignant melanoma presenting as a superior mediastinal mass. PMID- 22096740 TI - Duplication of vas deferens-A rare anomaly with review of literature. AB - INTRODUCTION: Isolated duplication of vas deferens is a rare anomaly with only eleven cases reported in medical literature. Unawareness regarding this rare anomaly can lead to inadvertent injury to the vas during inguinal hernia surgery or failure of vasectomy procedure. PRESENTATION OF CASE: A 27-year-old gentleman was diagnosed with isolated duplication of vas during left sided open inguinal hernia surgery. He had no other genito-urinary anomaly. Patient had an uneventful recovery from surgery. CONCLUSION: It is a rare anomaly and unawareness regarding this condition can lead to catastrophic consequences during inguinal hernia and vasectomy surgeries. PMID- 22096741 TI - Epigastirc hernia presenting as a giant abdominal interparietal hernia. AB - INTRODUCTION: Epigastric hernia is a rare form of ventral abdominal hernia. When neglected it can attain an impressive size causing it un-aesthetic effect in addition to diagnostic difficulties. PRESENTATION OF CASE: Presented is a 60-year old female farmer with a 10-year history of a voluminous mass in the anterior abdominal wall. DISCUSSION: Surgery revealed an epigastric hernia presenting as an interparietal hernia. The hernia was an omentocele with a grossly distended hernia sac filled with about 2.5 l of serous fluid. No similar case has been found in the medical literature. CONCLUSION: Epigastric hernia can attain voluminous dimensions and present as a non-inguinal interparietal hernia. PMID- 22096742 TI - Early cystic duct carcinoma of new classification. AB - INTRODUCTION: Classically defined cystic duct carcinoma is extremely rare owing to its strict diagnostic criteria, which are not suitable in actual clinical settings. Recently, several new classifications of cystic duct carcinoma were reported, which defined it as a tumor with its center located in the cystic duct. On the other hand, the incidence of cystic duct carcinoma, based on the new classifications, is not rare, but all reported cases are advanced. PRESENTATION OF CASE: A 77-year-old man with dilatation of the common bile duct, a stricture at the level of the cystic duct junction, and a filling defect of contrast medium into cystic duct in endoscopic retrograde cholangiopancreatography was diagnosed with cystic duct carcinoma. Radical cholecystectomy with bile duct resection was performed. In the resected specimen, we found that a 2 cm tumor whose center was located in the cystic duct and vertically limited to the mucosal layer. Horizontally, the tumor was superficially spread in the gallbladder, which were also limited to the mucosal layer. DISCUSSION: Here we report a first case of early cystic duct carcinoma diagnosed according to a new classification that had spread superficially into the gallbladder. When treating an early cystic duct carcinoma, it is important to note that even localized carcinoma can potentially invade into adjacent organs or metastasize to regional lymph nodes due to the location of cystic duct. CONCLUSION: It is suggested that perform radical resection such as cholecystectomy with gallbladder fossa resection, extrahepatic bile duct resection and regional lymphadenectomy is the treatment of choice. PMID- 22096743 TI - A rare complication of acute appendicitis: Superior mesenteric vein thrombosis. AB - INTRODUCTION: Very few cases of superior mesenteric vein thrombosis have been reported as a complication of appendicitis. In these handful of cases, the thrombosis was identified early with computerised tomography scan and patients have been managed conservatively with antibiotics and anticoagulation. PRESENTATION OF CASE: A 45-year-old gentleman presented to the emergency department with a 13-day history of right lower quadrant abdominal pain and rigors. CT scan of the abdomen revealed an appendicular mass and superior mesenteric vein thrombosis. The patient was initially managed by anticoagulation and antibiotics for two weeks and was discharged after satisfactory clinical improvement. He represented after discharge for increased severity of his abdominal pain and abnormal inflammatory markers. Emergency open appendicectomy for complicated appendicitis was performed and his postoperative course was unremarkable. He was discharged on the 7th postoperative day with anticoagulation. Outpatient review at two months was unremarkable. DISCUSSION: Acute appendicitis is a common surgical presentation where history and examination is key in clinching the diagnosis. Inflammatory markers and imaging modalities such as a CT scan can be helpful. Although surgical intervention is the mainstay of treatment, conservative management with antibiotics is an option if the diagnosis of appendicitis is equivocal. Recent evidence has revealed that elective appendicectomy is not necessary upon successful conservative management. Acute appendicitis can lead to local perforations and abscesses. Complications such as thrombosis in the superior mesenteric vein are rare and can be managed successfully with anticoagulants. CONCLUSION: Although this is a rare complication of appendicitis, the case was managed successfully with a conservative approach. This is inline with the general consensus which is to treat superior mesenteric vein thrombosis secondary to appendicitis conservatively unless the patient deteriorates. PMID- 22096744 TI - Extragastrointestinal Stromal Tumor (EGIST) in the abdominal wall: Case report and literature review. AB - INTRODUCTION: Gastro Intestinal Stromal Tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract (GI). GIST that arises primarily outside the GI tract is termed Extragastrointestinal Stromal Tumor (EGIST). To the best of our knowledge, few cases of EGIST in the abdominal wall were reported. PRESENTATION OF CASE: We present a rare case of EGIST in the abdominal wall of a 57 year-old female patient. The asymptomatic tumor was located in the superior aspect of the left rectus abdominis muscle, measured 5.4 * cm 5.3 * cm 6.9 cm and was well circumscribed. Histological examination showed an epithelioid cell morphology. The mitotic count was 7/50 HPFs. Immunohistochemistry showed diffuse strong CD117 positivity, focal positivity for S100. The tumor was excised and the margins were free of malignancy. The patient was doing well postoperatively and was discharged on STI-571 regimen. DISCUSSION: Although GIST is the most common mesenchymal tumor of the gastrointestinal tract, a case with EGIST in the abdominal wall is rare. Positive immunohistochemical staining for CD117 is a defining feature of GISTs. A great percentage of EGISTs represent a metastasis from a primary GIST. In our case, the clinical and diagnostic work-up have been proved it to be an EGIST. CONCLUSION: The existing data on EGIST is insufficient to make a final conclusion regarding the malignant potential and clinicopathological factors of EGISTs that determine patient prognosis. Thus a follow-up for a long period is required. EGISTs should be kept in mind in the differential diagnosis for patients presenting with solid mass of the abdominal wall. PMID- 22096745 TI - Angiodysplasia of the gallbladder. AB - INTRODUCTION: Angiodysplasia is a term used to describe distinct mucosal vascular ectasias found mainly in the gastrointestinal tract. Angiodysplasia of the gallbladder is exceedingly rare. PRESENTATION OF CASE: We encountered a patient who presented with biliary colic and subsequently underwent an elective laparoscopic cholecystectomy. The angiodysplasia of the gallbladder was found incidentally on histopathological examination of the excised gallbladder. DISCUSSION: Review of the literature showed only one other reported case of angiodysplasia of the gallbladder. The condition may be found incidentally after histopathological examination of the gallbladder removed for gallstone; or it may present with haemobilia. CONCLUSION: We presented an extremely rare case of angiodysplasia of the gallbladder, which was found incidentally after histopathological examination of the gallbladder removed for gallstone. Angiodysplasia of the gallbladder has the potential to bleed. Laparoscopic cholecystectomy is effective in providing a definitive cure. PMID- 22096746 TI - Angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma) of the face: An unusual presentation. AB - Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare entity that usually occurs as 0.5-3 cm pink to brown nodules in the skin surface and subcutaneous tissues of the head & neck. Here we report an unusual occurrence in size and appearance of ALHE in the tissues of the cheek of an adult Asian male. PMID- 22096747 TI - Iatrogenic liver trauma managed with mesh-wrapping and ligation of portal vein branch: A case report. AB - INTRODUCTION: Liver trauma is a critical condition that requires swift multidisciplinary approach. In complex hepatic injuries perihepatic packing is an established life-saving procedure. The aim of this study is to evaluate and highlight the value of absorbable mesh wrapping of the injured liver, combined with ipsilateral ligation of portal vein branch. CASE PRESENTATION: An 82-year old patient underwent an open cholocystectomy, for gallbladder empyema. The second postoperative day he was re-operated on due to active hemorrhage. The bleeding was controlled by suturing the bed of the gallbladder fossa. During this maneuver a portal vein branch was torn resulting in a rapidly expanding subcapsular liver hematoma which led to the formation of two deep lacerations on the liver parenchyma. This life-threatening condition was treated by wrapping an absorbable mesh around the right liver lobe and subsequently ligating the right portal vein branch extrahepaticaly. CONCLUSION: Mesh wrapping of the fragmented liver with absorbable mesh constitutes a safe and effective method, in treating grade IV and V liver injuries, especially when combined with ipsilateral ligation of the bleeding vessel. PMID- 22096748 TI - Vanek's tumour mimicking an acute appendicitis. AB - INTRODUCTION: Vanek's tumour or Inflammatory Fibroid Polyp (IFP) are rare, benign localised lesions originating from the sub-mucosa of the gastrointestinal tract (GI) tract.(1) They have been widely reported as occurring within the stomach, Duodenum, Jejunum and Ileum, more rarely (<1%) in the caecum or appendix. PRESENTATION OF CASE: We present a case of a 28-year-old lady who presented with a 2-day history of right iliac fossa pain, nausea and low-grade fever. Subsequent, ultrasonography (USS) of the abdomen demonstrated an inflamed tubular structure originating from caecum with fluid in the pelvis mimicking an acute appendicitis. Next to normal appendix an inflammatory polypoid mass was identified and on histological examination confirmed to be an IFP (Vanek's tumour). DISCUSSION: Right Iliac Fossa (RIF) pain with suspected appendicitis is one of the most common presentations in any acute surgical unit. In young women of childbearing age, the differential diagnosis can be varied and vast. The surgical management of IFP (Vanek's tumour) in such cases ranges from limited resection and caecectomy to limited right hemicolectomy. CONCLUSION: To date, the exact histiogenesis of these tumours remains unclear and requires a high level of intra-operative suspicion. According to our search such presentation is not reported. PMID- 22096749 TI - Middle-preserving pancreatectomy for synchronous ampullary carcinoma and solid pseudopapillary tumor of distal pancreas. AB - INTRODUCTION: Total pancreatectomy is the treatment of choice for multicentric diseases involving the pancreas. Middle-preserving pancreatectomy is a recently reported alternative procedure when the pancreatic body is spared from disease. PRESENTATION OF CASE: We report a 63-year old lady who underwent a combined Whipple's operation and distal splenopancreatectomy for her synchronous ampullary carcinoma and solid-pseudopapillary tumor of the distal pancreas. DISCUSSION: For multiple tumors of the pancreas, the choice of surgery should be based on the nature of pathology and follow the principle of oncological resection. CONCLUSION: Middle-preserving pancreatectomy is a safe and feasible option for patient with multicentric or synchronous pancreatic pathologies. PMID- 22096750 TI - Infertility and chylous ascites? A case report. AB - INTRODUCTION: Chylous ascites is defined by an accumulation of chylous fluid in the peritoneal cavity and it clinically appears as a milky fluid in which laboratory examination reveals triglycerides, cholesterol, and sometimes chylomicrons and lymphocytes. PRESENTATION OF CASE: We report the first case of primary chylous ascites observed during laparoscopy for unexplained secondary infertility. DISCUSSION: Chylous ascites has never been linked to fertility but bathes all internal reproductive organs surfaces and is considered a communication mean between ovaries. CONCLUSION: Despite a lack of evidence, the question of peritoneal fluid role remains in infertility. PMID- 22096751 TI - Short report of an unusual ballistic trauma. AB - INTRODUCTION: Portable firearms have a relevant medico-legal interest, being a major cause of injury. Bullet entry wounds generally have a particular appearance, including contusion, skin introflection, and simple or excoriated ecchymosis. The skin wound is typically a hole with frayed margins, whose diameter is smaller than that of the bullet. PRESENTATION OF CASE: We report the case of a 19-year-old man with ballistic trauma. Examination of the patient's lesions indicated that the bullet had entered from the left mandibular parasymphysis, creating a small hole without the typical bullet wipe and blackening. Subsequently, the bullet seemed to have fractured the left chin region immediately below the lower alveolar process, and it finally stopped in the submandibular area in the suprahyoid region of the neck. DISCUSSION: This case is peculiar because the distinctive features of a firearm injury were absent; the lack of bleeding and edema made the case difficult to interpret without additional diagnostic investigations. CONCLUSION: Ballistic trauma can manifest in different ways; therefore, internal trauma should be suspected even in the absence of clear external signs. This case report shows how an unusual bullet entry hole can mask quite serious injuries. PMID- 22096752 TI - Closed reduction of radius refracture: A case report. AB - INTRODUCTION: Refractures of the radius and ulna in the paediatric patient with flexible intramedullary nails in situ are known to occur. There are no formal guidelines currently in the literature to guide the management of such fractures. PRESENTATION OF CASE: A 10-year-old Caucasian girl, sustained a closed refracture of the radius at the same level, with the flexible intramedullary nails in situ to treat her recent ulna and radius fractures. DISCUSSION: We proposed a new non invasive way of reducing and maintaining such fractures without removal of the bent nail completely. CONCLUSION: This method does not significantly reduce the mechanical strength of the nail, as we do not advocate applying an external lateral force, which would compromise nail mechanical strength and eventually lead to breakage of the nail in situ. PMID- 22096753 TI - Robotic redo fundoplication for incompetent wrapping after antireflux surgery: A case report. AB - INTRODUCTION: Incidence of gastroesophageal reflux disease (GERD) is high. antireflux surgery with specific indications could be an option. Nissen fundoplication is the most popular surgical procedure for GERD, and recent results using laparoscopy have reported excellent short- and mid-term results. Regarding surgical outcome of antireflux surgery, the rate of complications has been reported as below 2.4%, but rare cases still require reoperation. PRESENTATION OF CASE: A 53-year old male patient underwent laparoscopic Nissen fundoplication three years ago owing to gastroesophageal reflux disease (GERD) troubled by dysphagia and heartburn However, despite undergoing surgery, his symptoms did not show improvement .A robotic redo fundoplication was planned. The patient recovered uneventfully, and the esophagography on postoperative day four revealed improvement of previous upward contrast reflux and distension of the distal esophagus during swallowing had disappeared. Dysphagia and heartburn had still not occurred at one year follow-up. DISCUSSION: Redo antireflux surgery for postoperative stricture is not an easy procedure due to postoperative adhesion and anatomical change. Robotic surgery may be more helpful for precise dissection of the adhesion site by a previous operation and robotic suturing for re fundoplication was more effective. CONCLUSION: Re-do fundoplication using a robot, which is a complicated procedure compared with primary anti-reflux surgery would be a general procedure in the near future. PMID- 22096754 TI - Early intervention in intersigmoid hernia may prevent bowel resection-A case report. AB - INTRODUCTION: Intersigmoid hernia is a rare internal hernia presenting with symptoms of bowel obstruction. Preoperative diagnosis is uncommon but computerised tomography (CT) may show signs to suggest internal hernia. PRESENTATION OF CASE: A 63-year-old female presented with abdominal pain, vomiting and absolute constipation. Examination revealed a tense distended abdomen. A plain abdominal radiograph showed features of small bowel obstruction. Conservative management was initiated without success and a CT scan was performed which showed a dilated distal oesophagus, stomach and small bowel with a non dilated length of distal ileum and large bowel. Internal hernia was suggested as a possible cause and the patient underwent a laparotomy where a loop of small bowel was found to be strangulated and gangrenous within the intersigmoid fossa. The gangrenous bowel was resected, an end-to-end anastamosis was performed and the fossa was closed. The patient made an uneventful recovery. DISCUSSION: Hernias of the sigmoid mesocolon account for 6% of internal hernias with internal hernias themselves causing between 0.2 and 4.1% of intestinal obstruction. This report presents a case of intersigmoid hernia, a rare internal hernia which should be suspected in patients presenting with acute obstruction, no past surgical history and no external hernia. Patients with these symptoms should receive an urgent CT scan to facilitate early surgery and minimise strangulation and prevent bowel resection. CONCLUSION: Intersigmoid hernia presents with acute obstruction, no past surgical history and no external hernia. Urgent CT scanning and early surgery may minimise strangulation, conserve bowel and reduce patient morbidity and mortality. PMID- 22096755 TI - Successful treatment of ventilator dependent emphysema with Chartis treatment planning and endobronchial valves. AB - INTRODUCTION: Emphysema is a leading cause of disability and death. Patients who require ventilator support as a result of respiratory failure have limited treatment options. We report a successful outcome for a ventilator dependent patient in whom endobronchial valves were inserted into lobes assessed as being without collateral ventilation. PRESENTATION OF CASE: A 54 year old male patient had been ventilator dependent for two months due to respiratory insufficiency from emphysema. Prior to admission, FEV(1) was 0.89L (25% predicted) and RV was 4.5L (205% predicted). CT scan showed destruction of right lower and middle lobes and left lower lobe. Chartis assessment showed the absence of collateral ventilation. Zephyr endobronchial valves were placed in left and right lower lobes. Lung volume reduction bilaterally was confirmed on chest X-ray and CT scan the following day. On day three, ventilator support was discontinued and there was no requirement for supplementary oxygen. At 30 days post procedure, the RV reduced to 3.2L (142% predicted) and the FEV(1) increased to 1.32L (38% predicted). DISCUSSION: Hyperinflation in emphysema compromises lung function. For this ventilator dependent patient, there were no other treatment options. Endoscopic lung volume reduction was successfully achieved by bilateral lower lobe placement of Zephyr endobronchial valves with a prior assessment using Chartis to determine the absence of collateral flow in the targeted lobes. The patient achieved an impressive 48% improvement in FEV(1) and a 29% reduction in RV. CONCLUSION: Endoscopic lung volume reduction assisted by Chartis to plan treatment resulted in a clinical and a health-economic benefit. PMID- 22096756 TI - Endometriosis in the canal of Nuck hydrocele: An unusual presentation. AB - The authors describe an unusual rare presentation of endometriosis in a hydrocoele of the canal of Nuck. A 43-year-old lady presented with a swelling in her right groin associated with mild discomfort. Examination revealed a cystic swelling in the groin for which she underwent an exploration and excision of the swelling. Surgery revealed a hydrocele of the canal of Nuck which was confirmed histologically. The unusual presentation of endometriosis in the sac was confirmed immunocytochemically. PMID- 22096757 TI - A pseudo-TEP repair of an incarcerated obturator hernia. AB - INTRODUCTION: Obturator hernia (OH) is a rare condition and difficult to diagnose. While they account for as few as 0.073% of all hernias, mortality can be as high as 70%. The typical clinical presentation for OH is small bowel obstruction. Computed tomography is the diagnostic tool of choice. Surgical repair is mandatory in virtually all cases of OH and traditionally consists of performing an exploratory laparotomy. PRESENTATION OF CASE: A 90-year-old female was admitted to our surgical service with signs of small bowel obstruction and a CT scan revealing incarcerated fatty tissue and small bowel within a left OH. DISCUSSION: The role of laparoscopic surgery in the management of OH has been limited to elective repairs; most reports detail that the OH was found serendipitously during laparoscopic inguinal hernia operations or other pelvic procedures. A few reports describe the use of laparoscopy to treat OH associated with bowel obstruction in an emergency setting using a TAPP approach. A strict TEP hernia repair is not indicated for all patients with OH, and should rarely be performed in emergency situations given its limitation to assess or resect bowel if necessary. In selected cases, a formal exploratory laparoscopy that is negative for compromised bowel can be safely followed by a TEP repair using the same umbilical access as shown in our patient. CONCLUSION: A 90-year-old female with a small bowel obstruction related to an incarcerated OH was treated effectively with an extraperitoneal laparoscopic approach. PMID- 22096758 TI - Intraabdominal desmoplastic small round cell tumor: Report of a case and literature review. AB - INTRODUCTION: Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. Due to our limited knowledge of the pathologic and clinical nature of this disease, there is no clear consensus regarding the optimal therapeutic procedures for treating this neoplasm. A high degree of care and improvements in diagnostic capabilities are required in order to identify this entity and avoid misdiagnosis. CASE PRESENTATION: We report a new case of a 29 year-old male who proceeded to our Emergency Department complaining about non specific abdominal pain. Physical examination revealed no abnormalities except for a palpable mass in the lower abdomen and a diffuse abdominal pain. Computed Tomography scan showed enlarged paraortic and mesenteric lymphadenopathy, thickness of the small bowel wall and dispersed masses intraperitoneally. He underwent an exploratory laparotomy and the resultant biopsy revealed desmoplastic small round cell tumor. DISCUSSION: Diagnosis of desmoplastic small round cell tumor can easily be missed because it presents with few early warning symptoms and signs, while the routine blood tests are within normal limits. CONCLUSION: A high degree of suspicion, a thorough physical examination, a full imaging check and an aggressive therapeutic approach are required in order to identify this disease and fight for a better quality of life for these patients. In addition we make a review of the literature in an effort to clarify the epidemiological, clinical and pathological aspects of this entity. PMID- 22096759 TI - Total neopharyngeal stenosis following pharyngolaryngo-oesophagectomy with gastric interposition: Successful recanalisation using a transcervical radiologically guided technique. AB - INTRODUCTION: Pharyngo-oesophageal stricturing is common following treatment of head and neck cancers. Absolute dysphagia secondary to total stenosis, although rare, is particularly debilitating and presents a significant therapeutic challenge. We present a strategy for managing total neopharyngeal stenosis following pharyngolaryngo-oesophagectomy (PLOG). PRESENTATION OF CASE: A 71-year old female developed total neopharyngeal stenosis following PLOG with gastric interposition for squamous cell carcinoma of the proximal cervical oesophagus/post-cricoid. A transcervical, percutaneous, radiologically guided procedure was performed to restore lumenal patency, which enabled resumption of oral feeding. DISCUSSION: Established treatments for pharyngo-oesophageal strictures are frequently limited by complications in patients with complex strictures or total stenoses. Whilst several interventions have been described, recent interest has focussed on combined antegrade/retrograde endoscopic procedures dilating a pre-existing gastrostomy site for access. This was not possible in our patient due to the surgically altered anatomy which posed a unique therapeutic challenge. CONCLUSION: This is the first reported percutaneous, transcervical, radiologically guided technique to treat neopharyngeal stenosis following PLOG. It demonstrates a novel and efficacious approach which may be considered in the management of this rare but significant complication. PMID- 22096760 TI - Case report and literature review: Metastatic lobular carcinoma of the breast an unusual presentation. AB - INTRODUCTION: Invasive lobular carcinoma is the second most common type of invasive breast carcinoma (between 5% and 15%). The incidence of invasive lobular carcinoma has been increasing while the incidence of invasive duct carcinoma has not changed in the last two decades. This increase is postulated to be secondary to an increased use of combined replacement hormonal therapy. Patients with invasive lobular carcinoma tend to be slightly older than those with non-lobular invasive carcinoma with a reported mean age of 57 years compared to 64 years. On mammography, architectural distortion is more common and microcalcifications less common with invasive lobular carcinoma than invasive ductal carcinoma. The incidence of extrahepatic gastrointestinal (GI) tract metastases observed in autopsy studies varies in the literature from 6% to 18% with the most commonly affected organ being the stomach, followed by colon and rectum. Gastric lesions seem to be slightly more frequent, compared to colorectal lesions (6-18% compared to 8-12%, respectively). PRESENTATION OF CASE: We present the case of a 70-year old woman who was referred to our institution with a concurrent gastric and rectal cancer that on further evaluation was diagnosed as metastatic invasive lobular carcinoma of the breast. She has a stage IV clinical T3N1M1 left breast invasive lobular carcinoma (ER positive at 250, PR negative, HER-2/neu 1+ negative) with biopsy proven metastases to left axillary lymph nodes, gastric mucosa, peritoneum, rectal mass, and bone who presented with a partial large bowel obstruction. She is currently being treated with weekly intravenous paclitaxel, bevacizumab that was added after her third cycle, and she is also receiving monthly zoledronic acid. She is currently undergoing her 12-month of treatment and is tolerating it well. Discussion Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women aged 20-59 years. It accounts for 26% of all newly diagnosed cancers in females and is responsible for 15% of the cancer-related deaths in women.(9) Breast cancer is one of the most common malignancies that metastasize to the GI tract, along with melanoma, ovarian and bladder cancer. CONCLUSION: We present one of the first reports of metastatic lobular breast cancer presenting as a synchronous rectal and gastric tumors. Metastatic lobular carcinoma of the breast is a rare entity with a wide range of clinical presentations. A high level of suspicion, repetition of endoscopic procedures, and a detailed pathological analysis is necessary for early diagnosis, which might help to avoid surgical treatment due to incorrect diagnosis. Patients with a history of breast cancer who present with new gastrointestinal lesions should have these lesions evaluated for evidence of metastasis through histopathologic evaluation and immunohistochemical analysis. Differentiating between a primary GI lesion and metastatic breast cancer will allow initiation of appropriate treatment and help prevent unnecessary operations. PMID- 22096761 TI - Adrenal pseudocyst: Diagnosis and laparoscopic management - A case report. AB - Cysts of the adrenal gland are rare and are usually discovered incidentally. Large adrenal cysts can however present with severe abdominal pain and can be complicated by haemorrhage, rupture or infection. Adrenal pseudocysts appear to result from haemorrhage within a normal adrenal gland and can expand to accommodate massive amounts of fluid.We report the case of a 39-year-old woman who presented with worsening right upper quadrant pain. An ultrasound scan of the abdomen confirmed a large 29 cm * 20 cm * 17 cm cyst that appeared to originate in the upper pole of the right kidney causing displacement of the liver and right kidney.Following complete aspiration the cyst re-accumulated and an MRI scan demonstrated a thickened and irregular cyst wall with haemorrhagic fluid. Laparoscopic right adrenalectomy was performed and the histopathological diagnosis was confirmed as an adrenal pseudocyst. PMID- 22096762 TI - Bilateral persistent sciatic arteries complicated with chronic lower limb ischemia. AB - INTRODUCTION: Persistent sciatic artery (PSA) is a rare vascular anomaly associated with a higher rate of aneurysm formation or thromboembolic complications causing lower extremity ischemia. PRESENTATION OF CASE: A 15-year old female patient with bilateral PSA presented with lower extremity ischemia. Considering the age and symptoms of the patient, we did not perform any intervention, but continued surveillance with duplex ultrasonography in case of the high incidence of aneurysmal formation or thromboembolic event. DISCUSSION: Epidemiology, development, anatomical structure, diagnosis and treatments of PSAs are discussed. CONCLUSION: PSAs, are prone to early atheromatous degeneration and aneurysm formation. Treatment of a PSA mainly dependent on the symptoms is either by surgical procedures or by endovascular interventions. PMID- 22096763 TI - Lingual thyroid: A case report. AB - INTRODUCTION: Lingual thyroid (LT) gland is a rare clinical entity which was found to occur due to the failure of the thyroid gland to descend to its normal cervical location during embryogenesis. The presence of an ectopic thyroid gland located at the base of the tongue may present with symptoms like dysphagia, dysphonia, upper airway obstruction or even hemorrhage at any time from infancy through adulthood. PRESENTATION OF CASE: We are presenting a case of 5-year-old girl who presented with lingual thyroid, treated with Suppression treatment followed by elective surgical resection. DISCUSSION: Incidence of ectopic lingual thyroid gland is reported as 1:100,000. It is more common in females. Most of presentations due to oropharyngeal obstruction, including dysphagia, dyspnea and dysphonia. Investigations include thyroid function tests, neck US, Technetium scanning and C.T. CONCLUSION: Lingual thyroid is a rare anomaly. Dysphagia and dysphonia are common presenting symptoms. Pathogenesis of this ectopic is unknown. Different types of surgical approaches have been described in the management. PMID- 22096764 TI - Diagnostic and therapeutic value of laparoscopy for small bowel blunt injuries: A case report. AB - INTRODUCTION: Small bowel injuries after blunt abdominal trauma represent both a diagnostic and a therapeutic challenge. Early diagnosis and prompt treatment are necessary in order to avoid a dangerous diagnostic delay. Laparoscopy can represent a diagnostic and therapeutic tool in patients with uncertain clinical symptoms. PRESENTATION OF THE CASE: We report the case of a 25-year-old man, haemodynamically stable, admitted for acute abdominal pain a few hours after a physical assault. Giving the persistence of the abdominal pain and the presence of free fluids at the computed tomography examination, an exploratory laparoscopy was performed. DISCUSSION: At the laparoscopic exploration, an isolated small bowel perforation was found, 60 cm distal from the ligament of Treitz. The injury was repaired by laparoscopic suturing and the patient was discharged home at postoperative day 3 after an uneventful postoperative course. CONCLUSIONS: Laparoscopy represents a valuable tool for patients with small bowel blunt injuries allowing a timely diagnosis and a prompt treatment. PMID- 22096765 TI - Our philosophy. PMID- 22096766 TI - Whats new in critical illness and injury science ? Mapping and tracking glucose levels in critical patients. PMID- 22096767 TI - The glucogram: A new quantitative tool for glycemic analysis in the surgical intensive care unit. AB - BACKGROUND: Glycemic control is an important aspect of patient care in the surgical intensive care unit (SICU). This is a pilot study of a novel glycemic analysis tool - the glucogram. We hypothesize that the glucogram may be helpful in quantifying the clinical significance of acute hyperglycemic states (AHS) and in describing glycemic variability (GV) in critically ill patients. MATERIALS AND METHODS: Serial glucose measurements were analyzed in SICU patients with lengths of stay (LOS) >30 days. Glucose data were formatted into 12-hour epochs and graphically analyzed using stochastic and momentum indicators. Recorded clinical events were classified as major or minor (control). Examples of major events include cardiogenic shock, acute respiratory failure, major hemorrhage, infection/sepsis, etc. Examples of minor (control) events include non-emergent bedside procedures, blood transfusion given to a hemodynamically stable patient, etc. Positive/negative indicator status was then correlated with AHS and associated clinical events. The conjunction of positive indicator/major clinical event or negative indicator/minor clinical event was defined as clinical "match". GV was determined by averaging glucose fluctuations (maximal - minimal value within each 12-hour epoch) over time. In addition, event-specific glucose excursion (ESGE) associated with each positive indicator/AHS match (final minus initial value for each occurrence) was calculated. Descriptive statistics, sensitivity/specificity determination, and student's t-test were used in data analysis. RESULTS: Glycemic and clinical data were reviewed for 11 patients (mean SICU LOS 74.5 days; 7 men/4 women; mean age 54.9 years; APACHE II of 17.7 +/- 6.44; mortality 36%). A total of 4354 glucose data points (1254 epochs) were analyzed. There were 354 major clinical events and 93 minor (control) events. The glucogram identified AHS/indicator/clinical event "matches" with overall sensitivity of 84% and specificity of 65%. We noted that while the mean GV was greater for non-survivors than for survivors (19.3 mg/dL vs. 10.3 mg/dL, P = 0.02), there was no difference in mean ESGE between survivors (154.7) and non survivors (160.8, P = 0.67). CONCLUSIONS: The glucogram was able to quantify the correlation between AHS and major clinical events with a sensitivity of 84% and a specificity of 65%. In addition, mean GV was nearly two times higher for non survivors. The glucogram may be useful both clinically (i.e., in the electronic ICU or other "early warning" systems) and as a research tool (i.e., in model development and standardization). Results of this study provide a foundation for further, larger-scale, multi-parametric, prospective evaluations of the glucogram. PMID- 22096768 TI - Resource utilization in the management of traumatic brain injury patients in a critical care unit: An audit from a rural set-up of a developing country. AB - BACKGROUND: Neurosurgical patients including patients with severe head injury are at risk of developing respiratory complications. These can adversely affect the outcome and can result in poor survival. Many studies confirm that tracheostomy is a safe, effective method of airway management for patients with severe head, facial and multisystem organ trauma. AIMS: To know the indications for performing early tracheostomy and its outcome. SETTINGS AND DESIGN: Retrospective data analysis. MATERIALS AND METHODS: The present study is a retrospective analysis of all patients who were admitted with the diagnosis of head injury between January 2007 and December 2009 and underwent tracheostomy at a rural tertiary care trauma center of Central India. RESULTS: During the study period, a total of 40 patients with head injury underwent tracheostomy. All the patients sustained head injury in road traffic accidents. The mean age of the patients was 37.6 years (range 14 75 years, standard deviation 14 +/- 14.9 years). Maximum number of patients were in their third decade of life, followed by those in the fifth and fourth decades. There were 36 males and 4 females. Tracheostomy was performed in 30 patients with severe head injury, 9 patients with moderate head injury and in only one case of mild head injury as the patient had multiple facial injuries compromising the airway. CONCLUSIONS: Neurocritical care is a relatively new field in India, and the facilities for critical neurosurgical patients are available only in a very few tertiary care centers mainly serving the urban areas. In the present study, we discuss our limited experience with tracheostomy in patients with head injury while facing the challenge of limited resources. PMID- 22096769 TI - Risk factors for aminoglycoside-associated nephrotoxicity in surgical intensive care unit patients. AB - BACKGROUND: Aminoglycosides are commonly used antibiotics in the intensive care unit (ICU), but are associated with nephrotoxicity. This study evaluated the development of aminoglycoside-associated nephrotoxicity (AAN) in a single surgical intensive care unit. MATERIALS AND METHODS: Adult patients in our surgical ICU who received more than two doses of aminoglycosides were retrospectively reviewed for demographics, serum creatinine, receipt of nephrotoxins [angiotensin converting enzyme (ACE) inhibitors, angiotensin-II receptor blockers, diuretics, non-steroidal anti-inflammatory drugs, cyclosporine, tacrolimus, vasopressors, vancomycin and intravenous iodinated contrast] and the need for dialysis. AAN was defined as an increase in serum creatinine >0.5 mg/dL on at least 2 consecutive days. Univariate and multiple regression analyses were performed. RESULTS: Sixty-one patients (43 males) receiving aminoglycoside were evaluated. Mean age, weight, initial serum creatinine, and duration of aminoglycoside therapy were 58.7 (+/-15) years, 83.3 (+/-24.4) kg, 0.9 (+/-0.5) mg/dL, and 4 (+/-2.3) days, respectively. Thirty-one (51%) aminoglycoside recipients also received additional nephrotoxins. Seven aminoglycoside recipients (11.5%) developed AAN, four of whom required dialysis and all had received additional nephrotoxins. Only concurrent use of vasopressors (P = 0.041) and vancomycin (P = 0.002) were statistically associated with AAN. Receipt of vasopressors or vancomycin were independent predictors of acute kidney insufficiency (AKI) with odds ratios of 19.9 (95% CI: 1.6-245, P = 0.019) and 49.8 (95% CI: 4.1-602, P = 0.002), respectively. Four patients (6.6%) required dialysis. CONCLUSIONS: In critically ill surgical patients receiving aminoglycosides, AAN occurred in 11.5% of the patients. Concurrent use of aminoglycosides with other nephrotoxins increased the risk of AAN. PMID- 22096770 TI - Trauma care today, what's new? AB - Injury is the fourth leading cause of death in the US, and the leading cause of death in younger age. Trauma is primarily a disease of the young and accounts for more years of productive life lost than any other illness. Consequently, almost every health care provider encounters trauma patients from time to time. Many of these patients are critically ill and pose several challenges in the acute phase, including airway and ventilation, fluid management, intracranial pressure control, etc. In the last decade, several strategies and treatment options have been studied in trauma care along with improvement in technologies. In this review, we will discuss a few of the new developments and updates in trauma care. PMID- 22096771 TI - Perioperative management of traumatic brain injury. AB - Traumatic brain injury (TBI) is a major public health problem and the leading cause of death and disability worldwide. Despite the modern diagnosis and treatment, the prognosis for patients with TBI remains poor. While severity of primary injury is the major factor determining the outcomes, the secondary injury caused by physiological insults such as hypotension, hypoxemia, hypercarbia, hypocarbia, hyperglycemia and hypoglycemia, etc. that develop over time after the onset of the initial injury, causes further damage to brain tissue, worsening the outcome in TBI. Perioperative period may be particularly important in the course of TBI management. While surgery and anesthesia may predispose the patients to new onset secondary injuries which may contribute adversely to outcomes, the perioperative period is also an opportunity to detect and correct the undiagnosed pre-existing secondary insults, to prevent against new secondary insults and is a potential window to initiate interventions that may improve outcome of TBI. For this review, extensive Pubmed and Medline search on various aspects of perioperative management of TBI was performed, followed by review of research focusing on intraoperative and perioperative period. While the research focusing specifically on the intraoperative and immediate perioperative TBI management is limited, clinical management continues to be based largely on physiological optimization and recommendations of Brain Trauma Foundation guidelines. This review is focused on the perioperative management of TBI, with particular emphasis on recent developments. PMID- 22096772 TI - Anesthetic considerations in acute spinal cord trauma. AB - Patients with actual or potential spinal cord injury (SCI) are frequently seen at adult trauma centers, and a large number of these patients require operative intervention. All polytrauma patients should be assumed to have an SCI until proven otherwise. Pre-hospital providers should take adequate measures to immobilize the spine for all trauma patients at the site of the accident. Stabilization of the spine facilitates the treatment of other major injuries both in and outside the hospital. The presiding goal of perioperative management is to prevent iatrogenic deterioration of existing injury and limit the development of secondary injury whilst providing overall organ support, which may be adversely affected by the injury. This review article explores the anesthetic implications of the patient with acute SCI. A comprehensive literature search of Medline, Embase, Cochrane database of systematic reviews, conference proceedings and internet sites for relevant literature was performed. Reference lists of relevant published articles were also examined. Searches were carried out in October 2010 and there were no restrictions by study design or country of origin. Publication date of included studies was limited to 1990-2010. PMID- 22096773 TI - Advances in prehospital trauma care. AB - Prehospital trauma care developed over the last decades parallel in many countries. Most of the prehospital emergency medical systems relied on input or experiences from military medicine and were often modeled after the existing military procedures. Some systems were initially developed with the trauma patient in mind, while other systems were tailored for medical, especially cardiovascular, emergencies. The key components to successful prehospital trauma care are the well-known ABCs of trauma care: Airway, Breathing, Circulation. Establishing and securing the airway, ventilation, fluid resuscitation, and in addition, the quick transport to the best-suited trauma center represent the pillars of trauma care in the field. While ABC in trauma care has neither been challenged nor changed, new techniques, tools and procedures have been developed to make it easier for the prehospital provider to achieve these goals in the prehospital setting and thus improve the outcome of trauma patients. PMID- 22096774 TI - Trends in trauma transfusion. AB - Trauma is the leading cause of death in young adults and acute blood loss contributes to a large portion of mortality in the early post-trauma period. The recognition of lethal triad of coagulopathy, hypothermia and acidosis has led to the concepts of damage control surgery and resuscitation. Recent experience with managing polytrauma victims from the Iraq and Afghanistan wars has led to a few significant changes in clinical practice. Simultaneously, transfusion practices in the civilian settings have also been extensively studied retrospectively and prospectively in the last decade. Early treatment of coagulopathy with a high ratio of fresh frozen plasma and platelets to packed red blood cells (FFP:platelet:RBC), prevention and early correction of hypothermia and acidosis, monitoring of hemostasis using point of care tests like thromoboelastometry, use of recombinant activated factor VII, antifibrinolytic drugs like tranexamic acid are just some of the emerging trends. Further studies, especially in the civilian trauma centers, are needed to confirm the lessons learned in the military environment. Identification of patients likely to need massive transfusion followed by immediate preventive and therapeutic interventions to prevent the development of coagulopathy could help in reducing the morbidity and mortality associated with uncontrolled hemorrhage in trauma patients. PMID- 22096775 TI - Current trends and update on injury prevention. AB - Injuries are a major and growing public health problem, a leading cause of death and disabilities among people aged 1-44 years around the world. Each year, 5.8 million people die from injuries, accounting for 10% of the world's deaths. Road traffic injuries (RTIs), self-inflicted injuries and violence are the top three leading causes of all injury deaths, while RTIs, falls and drowning are the top three leading causes of unintentional injury death. In many high-income countries, trends of injury death have been decreasing as a result of prevention measures. In contrast, trends in low- and middle-income countries have been rising. In this article, we review the prevention strategies for RTIs, violence, falls and drowning developed over decades to disseminate the knowledge and inform health care providers, especially acute care physicians, about the importance of injury prevention. PMID- 22096777 TI - Acute ischemic colitis secondary to air embolism after diving. AB - Ischemic colitis (IC) secondary to air embolism from decompression sickness or barotrauma during diving is an extremely rare condition. After extensive review of the available literature, we found that there has been only one reported case of IC secondary to air embolism from diving. Although air embolization from diving and the various medical complications that follow have been well documented, the clinical manifestation of IC from an air embolism during diving is very rare and thus far unstudied. Common symptoms of IC include abdominal pain, bloody or non-bloody diarrhea or nausea or vomiting or any combination. Emergency physicians and Critical Care specialists should consider IC as a potential diagnosis for a patient with the above-mentioned symptoms and a history of recent diving. We report a case of IC from air embolism after a routine dive to 75 feet below sea level in a 53-year-old White female who presented to a community Emergency Department complaining of a 2-day history of diffuse abdominal pain and nausea. She was diagnosed by colonoscopy with biopsies and treated conservatively with antibiotics, bowel rest, and a slow advancement in diet. PMID- 22096776 TI - Damage control in the injured patient. AB - The damage control concept is an essential component in the management of severely injured patients. The principles in sequence are as follows: (1) abbreviated surgical procedures limited to haemorrhage and contamination control; (2) correction of physiological derangements; (3) definitive surgical procedures. Although originally described in the management of major abdominal injuries, the concept has been extended to include thoracic, vascular, orthopedic, and neurosurgical procedures, as well as anesthesia and resuscitative strategies. PMID- 22096778 TI - Treatment of an intraoral bleeding in hemophilic patient with a thermoplastic palatal stent - A novel approach. AB - This is a case report of a 13-year old child diagnosed with hemophilia A. He reported with a bleeding wound in the middle part of the hard palate, due to trauma from a lead pencil. An intraoral palatal stent was planned to provide continuous pressure, stabilize the clot and allow local delivery of hemostatic agent. The stent was fabricated with a thermoplastic silicone rubber (biostar) under vacuum. The hemostatic agent used was one 500 mg capsule of tranxemic acid that was crushed and applied as a paste every 6 hourly. The patient was admitted under supervision for 3 days, where Recombinant factor VIII (rFVIII) intravenous infusion of 15-25 U/kg twice a day was given. Complete healing was observed in the traumatized area within 10 days. This article emphasizes on prenatal diagnosis, carrier screening and counseling of parents born with hemophilic children. PMID- 22096779 TI - Propofol infusion syndrome in a super morbidly obese patient (BMI = 75). AB - Propofol infusion syndrome (PRIS) is a rare but often fatal complication as a result of large doses of propofol infusion (4-5 mg/kg/hr) for a prolonged period (>48 h). It has been reported in both children and adults. Besides large doses of propofol infusion, the risk factors include young age, acute neurological injury, low carbohydrate and high fat intake, exogenous administration of corticosteroid and catecholamine, critical illness, and inborn errors of mitochondrial fatty acid oxidation. PRIS manifestation include presence of metabolic acidosis with a base deficit of more than 10 mmol/l at least on one occasion, rhabdomyolysis or myoglobinuria, acute renal failure, sudden onset of bradycardia resistant to treatment, myocardial failure, and lipemic plasma. The pathophysiology of PRIS may be either direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. We report a case of supermorbidly obese patient who received propofol infusion by total body weight instead of actual body weight and developed PRIS. PMID- 22096780 TI - Unwashed doctors. PMID- 22096781 TI - Direct hapten-linked competitive inhibition enzyme-linked immunosorbent assay (CIELISA) for the detection of O-pinacolyl methylphosphonic acid. AB - Immunoassay detection of O-pinacolyl methylphosphonic acid (PMPA) employing direct coating of N-2-aminoethyl-O-pinacolyl methylphosphonate (hapten B) on microtiter plates is reported. Coating was achieved by covalently linking hapten B to a glutaraldehyde (GA) polymer network directly bound to the polystyrene (PS) surface of a standard 96-well microtiter plate. 4-(2-(O-Pinacolylmethylphosphoryl amino)ethyl amino)-4-oxobutanoic acid (hapten A)-ovalbumin (OVA) conjugate served as the coating antigen for comparison with direct hapten B-coated plates in the CIELISA format. The developed assay employing direct hapten B coated plates demonstrated enhanced sensitivity with the IC(50) value for PMPA being 0.027 MUg mL(-1). The assay could detect PMPA even at the concentration of 0.006 MUg mL( 1). The mean recovery of standard PMPA (spiked in water) was found to be 83.7%. PMID- 22096782 TI - HIV epidemic among U.S black women increasing at disturbing pace. 'The statistics are mind-boggling'. PMID- 22096783 TI - Mother-daughter power in DC program for girls. Focus on self-empowerment. PMID- 22096784 TI - MSM of color need HIV men's health leadership. Their infection rates are up. PMID- 22096785 TI - Cephalosporin-resistant gonorrhea: it's just a matter of time. PMID- 22096787 TI - Research explores at-home HIV testing. PMID- 22096788 TI - New condoms eyed for men, women. PMID- 22096786 TI - HIV prevention in serodiscordant pair. PMID- 22096789 TI - Populations at greatest risk. PMID- 22096790 TI - Funding. AIDS response by donor government declines. PMID- 22096791 TI - Research. Partner abuse increases infection risk in black women, teenagers. PMID- 22096792 TI - Research. Symptom-based screening could reduce MSM infections. PMID- 22096793 TI - Study finds HIV spreading to Pakistan's general population. PMID- 22096794 TI - CDC prevention programs tailored to women of color. PMID- 22096795 TI - Benefits. Veteran could not show he contracted HIV while in service. PMID- 22096796 TI - Employment. Worker with HIV could not support emotional distress claims. PMID- 22096797 TI - Plan administrator had reasons to terminate man's benefits. PMID- 22096798 TI - ADA. Worker failed to show he could perform functions of job. PMID- 22096799 TI - Findings of research misconduct. PMID- 22096800 TI - [Progression of surgical treatment]. PMID- 22096801 TI - [Progression of chemotherapy]. PMID- 22096802 TI - International study of a continence device with 12-hour wear times. AB - This international, phase III, 215-day, open-label, non-randomized, multicentre study assessed the safety and efficacy of 12-hour wear times with a novel colostomy continence control device in participants with end colostomies. Study stages were usual pouching (21 days), wafer transition (14 days), device 'ramp up' for 4, 6, and 8 hours (21 days), and 12-hour device wear (159 days). Of the 78 participants enrolled, 66 wore at least one device, and 45 completed treatment. Median device wear time was 11 hours per day during the final stage. Adverse events were reported by 12%, 7%, and 56% of participants during the usual pouching stage (0.01 events per participant per day), wafer transition stage, and device-wear stages (0.01 events per participant per day), respectively. No detrimental effects were seen on stoma vascularity or the normal gastrointestinal flora. The daily leakage-free rate was 0.89 for any leakage and 0.93 for type 2 leakage (e.g. not contained under the wafer). Most participants (87%) rated the ability of the device to restore continence as 'good' or 'very good'. Overall, the study showed that the continence control device was safe and effective for wear times up to 12 hours per day in colostomy patients. PMID- 22096803 TI - Peristomal skin irritation and the use of a silicone-based barrier film. AB - Maintaining skin integrity is vital to ensure good adhesion of the stoma pouch, and to avoid discomfort for the person with a stoma, ensuring a good quality of life. However, there are many risk factors associated with potential peristomal skin soreness, and a large number of research studies have highlighted the vast number of patients who actually experience these problems (Mahjoubi, 2005; Ratliff et al, 2005; Herlufsen et al, 2006; Lynch et al, 2008; Meisner and Balleby, 2008). Clinical nurse specialists in stoma care are responsible for ensuring that all patients are fully assessed, and also that patients are given appropriate evidence-based care to avoid peristomal skin irritation, where possible. This article will discuss the common causes of peristomal skin breakdown, the tools available to assist with assessment, and how to best treat peristomal skin irritation. PMID- 22096804 TI - Improving patient care after stoma reversal. AB - This article will examine the current service provision for patients who have had a temporary stoma reversal. Findings of a patient survey will be presented, highlighting the support and information received by 27 patients following a stoma reversal operation. Associated literature (Camilleri-Brennan and Steele, 2000; Sailer at al, 2000; Desnoo and Faithfull, 2006; Siassi et al, 2008; Chow et al, 2009) has confirmed a high likelihood of altered bowel function after stoma reversal, but makes less reference to the care that these patients require during the follow-up period. It is recommended that colorectal teams discuss the care implications for patients requiring stoma reversal, and appraise their care delivery to ensure patient needs are met. PMID- 22096805 TI - Second primary peristomal carcinoma: a case study. AB - Literature has highlighted that peristomal skin problems are common among ostomists (Williams et al, 2010); however, peristoma metastases are considered to be very rare. Peristomal metastases tend to manifest as cutaneous or subcutaneous nodules, or as a rash on the anterior abdominal wall (Lyon and Smith, 2001), and are therefore easily mistaken for a more common stoma complication. The role of the specialist nurse in stoma care is crucial to recognizin unusual skin lesions and referring appropriately for further assessmet and treatment. Highlighting the need for education and sharing of clinical skills, this article explores the care of a patient who was diagnosed with a second primary peristomal adenocarinoma. The patient has consented to the use of this case study, and, to maintain confidentiality, his name has been changed. PMID- 22096806 TI - Matching the skin barrier to the skin type. AB - Peristomal skin problems are thought to be common (Herlufsson et al, 2006; Williams et al, 2010), and can interfere with the security of stoma products. Stoma patients are reliant on the integrity of their peristomal skin to maintain a normal lifestyle. Bekkers et al (1996) highlighted that, if the peristomal skin becomes damaged, it not only affects the person physically, but also psychologically, ultimately prolonging rehabilitation and adaptation to the stoma. Therefore, it can be concluded that maintaining skin integrity is a basic and essential skill in ensuring good stoma management. This article explores the assessment of four stoma patients, highlighting the importance of matching their skin type with their skin barrier for optimum skin protection. The patients have kindly agreed for their case studies to be published as a means of informing others. All names have been changed in line with Nursing and Midwifery Council (2010) guidelines to maintain patient confidentiality. This article was originally presented at the World Council of Enterostomal Therapists' (WCET) annual conference in 2010, receiving first prize at poster presentations. PMID- 22096807 TI - Acknowledge your true value as a specialist nurse. PMID- 22096808 TI - No clinical relevance of approved animal experiments after seventeen years. PMID- 22096809 TI - SATIS ethics ranking of universities in Germany regarding animal use in education. PMID- 22096810 TI - The composition and morphology of yeast nuclear scaffolds. AB - The yeast nuclear scaffold has been shown to bind with high affinity to genomic sequences that permit autonomous DNA replication of plasmids (ARS elements). We describe here conditions for the isolation of a histone-free nuclear substructure, the nuclear scaffold, from Saccharomyces cerevisiae. We examine the protein composition of this structure,and the conditions under which topoisomerase II, the nuclear factor RAP-1 and RNA polymerase II co-fractionate with the scaffold. We find that exposure of nuclei to a combined metal and heat treatment (0.5mM Cu(2) +, 37 degree centigrade prior to detergent extraction is required for effective stabilization of these proteins with the scaffold. Electron microscopy of the residual nuclei extracted with non-ionic detergents shows the absence of a typical peripheral lamina structure. PMID- 22096811 TI - Glutamine requirement for aerial mycelium growth in Neurospora crassa. AB - Five amino acids are accumulated during vegetative growth of Neurospora crassa, particularly.during the prestationary growth phase. Alanine, glutamine, glutamate, arginine and ornithine.comprised over 80% of the total amino acid pool in the mycelium. Amino acid pools of different amino acid auxotrophs were followed during the partial transformation of a mycelial mat into an aerial mycelium. The mycelial mat under starvation and in direct contact with air rapidly formed aerial mycelium, which produced thereafter a burst of conidia. During this process,glutamine and alanine in the mycelial mat were consumed more rapidly than other amino acids;in the growing aerial mycelium, glutamate and glutamine were particularly accumulated. Of the amino acids that were initially accumulated in the mycelial mat, only a high glutamine pool was required for aerial mycelium growth induced by starvation. This requirement for glutamine could not be satisfied by a mixture of the amino compounds that are synthesized via glutamine amidotransferase reactions. It is proposed that glutamine serves as a nitrogen carrier from the mycelial mat to the growing aerial mycelium. PMID- 22096812 TI - Glutamine metabolism during aerial mycelium growth of Neurospora crassa. AB - During vegetative growth, glutamine is accumulated in the mycelium of Neurospora crassa. This high pool of glutamine seems to be required for aerial mycelium growth. Enzymes responsible for the synthesis and catabolism of glutamine were measured before and during the partial transformation of a mycelial mat into aerial mycelium. In the transforming mycelial mat,considerable activities of the biosynthetic NADP-glutamate dehydrogenase and glutamine synthetase (predominantly beta polypeptide) and also some activity of glutamate synthase were observed. In the aerial mycelium, glutamine synthetase (predominantly beta polypeptide) was detected, but very low activities of NADP-glutamate dehydrogenase and glutamate mycelium could derive from glutamine. No glutaminase activity could be detected. It is suggested that glutamate is formed through the activities of the glutamine transaminase-omega -amidase pathway and another transaminase. High activities of glutamine and alanine transaminases were observed in the aerial mycelium. These results are discussed in terms of the possible role of glutamine as a nitrogen carrier from the mycelium to the growing aerial hyphae. PMID- 22096813 TI - NZNO is in good heart and health. PMID- 22096814 TI - Cultivating empathy--nursing's core. PMID- 22096815 TI - Ens part of perioperative team too. PMID- 22096816 TI - Experiencing family-centred care. PMID- 22096817 TI - Nursing practising certificate restored. PMID- 22096819 TI - Working to close the gaps in health equity and access. PMID- 22096818 TI - Recording Canterbury nurses' history. PMID- 22096820 TI - Supporting nurses to provide primary mental health care. PMID- 22096821 TI - Treating adolescent depression with cognitive behaviour therapy. PMID- 22096823 TI - Political neutrality must not be used to stifle debate. PMID- 22096822 TI - Blood and hypertension: the damage of too much pressure. PMID- 22096824 TI - Nurses' contribution following an emergency. PMID- 22096825 TI - Time to rethink health spending. PMID- 22096826 TI - Giving evidence: a gruelling process. PMID- 22096827 TI - UK's obesity epidemic 'cannot be fixed with a one-size-fits-all' solution. PMID- 22096829 TI - Public health White Paper and transfer from NHS trusts to local authorities. PMID- 22096828 TI - Doubts about policy, the will to fight and union support. PMID- 22096830 TI - SRE for primary children. Resources for the delivery of sex and relationship education. PMID- 22096831 TI - Charities: cuts and crisis. PMID- 22096832 TI - The TwF project: promoting bilingualism for public health in Wales. AB - The Twf project was established in Wales in 2001 with the overall aim to increase the transfer of the Welsh language within the family. The project has two main strategies, which are to work with midwives and health visitors in order that they can inform parents of the advantages of raising children bilingually, and to raise awareness among parents-to-be, parents and the general public of the advantages of raising children bilingually. The project is funded by the Welsh government through the Welsh Language Board, and its community workers provide health visitors, midwives and other partners within their areas with Twf resources and information about relevant research, and visit antenatal and postnatal clinics on a regular basis to talk to parents. Where a particular need is identified, the Twf worker runs groups for new parents and parents-to-be to help them to speak Welsh to the baby through interesting activities, such as baby massage, singing and stories. PMID- 22096833 TI - Childcare support at nursery schools in Japan: current services and future needs. AB - This study aimed to survey childcare support being undertaken by nursery school teachers in Japan and to identify the theories and skills necessary for nursery school teachers to carry out childcare support in the future. In 2007, a postal questionnaires was sent to 1200 teachers at 850 nursery schools, with responses from 712 teachers from 456 nursery schools. In terms of knowledge and skills considered necessary by nursery school teachers in local childcare support centers, 'knowledge and skills of giving advice' was the most common response, followed by 'understanding of children's growth and development'. Nursery school teachers need to receive sufficient education before and after graduation to gain these skills. It is also clear that there is a need for nursery school teachers to make use of their expertise by co-ordinating collaboration among professionals and in the community. PMID- 22096834 TI - Brutal and negligent? 19th century factory mothers and child care. AB - This paper aims to highlight some working class women's childcare practices in northern industrial areas of Britain during the latter half of the 19th century. It aims to challenge the commonly held belief that 19th century northern working class factory mothers were irresponsive and neglectful toward their infants, thereby fuelling the high northern infant mortality rate. It will do this by showing that factory mothers were responsible and responsive toward their infants despite being thwarted by the working patterns of industrialisation. It begins by outlining the arguments made by historians that northern working class women were neglectful toward their children. Then key areas such as the working patterns of waged factory mothers will be illustrated to show the agency and determination of 19th century working class women to provide their infants with good care. Reassessment of these historical childcare practices can provide a springboard by which today's health professionals can endeavour to maintain accurate and fair perspectives about the childcare practices of today's women of low socio-economic status. PMID- 22096835 TI - Lactational amenorrhoea method contraception: improving knowledge. AB - Lactational amenorrhoea method (LAM) is a reliable form of contraception for up to six months following childbirth, provided the mother's periods have not returned and she is breastfeeding exclusively with sufficient feeds and no dummy or bottle use. This paper considers how LAM works and how it may be supported in practice, and provides a local example involving the use of information provision and training to overcome barriers to its understanding and use. An information leaflet was produced based on national guidance and with input from local practitioners and women. Brief training was also used to help ensure that women receive consistent and up-to-date information from health professionals. PMID- 22096836 TI - Sport in the park. PMID- 22096837 TI - Baby Friendly education. PMID- 22096838 TI - Flu fighter: push to vaccinate more NHS staff in the community. PMID- 22096839 TI - Theft and embezzlement: 10 steps to prevent it. PMID- 22096840 TI - Patient reviews on the Internet. PMID- 22096841 TI - Uplifting one generation to the next. PMID- 22096842 TI - Workers' compensation overview. PMID- 22096843 TI - Web browsers. PMID- 22096845 TI - Di-ag-KNOW-sis. PMID- 22096844 TI - It must be in the genes! Interview by Ernest Scheerer, Jr. PMID- 22096846 TI - Its not a crisis. PMID- 22096848 TI - [The interventions effect-assessment of the workers exposed to N, N dimethylformamide by percutaneous in a synthetic leather factory]. AB - OBJECTIVE: To assess the effects of interventions on synthetic leather workers exposed to N, N-dimethylformamide (DMF) by skin. METHODS: Twenty-six workers exposed to DMF were recruited. The level of DMF in ambient or handwash solution and N-methylformamide (NMF) in end-shift urine samples were detected before interventions and after interventions for six months. RESULTS: After interventions the levels of DMF in ambient reduced 52.7% from (63.27 +/- 52.67) mg/m3 to (29.95 +/- 23.79) mg/m3. The levels of NMF in urine samples reduced 17.9% from (2.07 +/- 0.32) mg/g Cr to (1.70 +/- 0.29) mg/g Cr (P < 0.01). The mean level of DMF in handwash solution reduced 53.4% from 0.88 +/- 0.40 mg to 0.41 +/- 0.81 mg. CONCLUSION: This study showed that the multi-intervention measures (engineering control, personal protection and health promotion) should be used for the synthetic leather workers occupationally exposed to DMF. PMID- 22096847 TI - [Association between polymorphisms of metabolic genes and telomere length in workers exposed to polycyclic aromatic hydrocarbon]. AB - OBJECTIVE: To investigate the association between the polymorphisms of metabolic genes and telomere length of genomic DNA in peripheral blood of workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: One hundred and forty five coke-oven workers exposed to PAHs and sixty eight non-exposed medical staffs were recruited in this study. Urinary 1-hydroxypyrene (1-OHP) served as the internal exposure dose of PAHs for all subjects. Relative telomere length (RTL) of genomic DNA in peripheral blood was used as telomere length and measured by real-time PCR. Polymorphisms of metabolic genes were detected by PCR-based methods. RESULTS: Compared with control group, the exposure group shown a decreased RTL (1.10 +/- 0.75 vs 1.43 +/- 1.06, P < 0.05). In the coke-oven workers, after adjusting the sex, age, cigarettes per day and urinary 1-OHP, RTL (1.25 +/- 0.93) of workers with CT genotype at the CYP1A1 3801 T > C was significantly longer than that (0.93 +/- 0.51) of workers with TT genotype (P < 0.05). RTL (0.90 +/- 0.58) of individuals with the Tyr/His genotype at mEH Tyr113His was significantly shorter than that (1.24 +/- 0.90) of individuals with the Tyr/Tyr genotype (P < 0.05). RTL (1.02 +/- 0.64) of individuals with the CT genotype at AHR rs10250822 was significantly shorter than that (1.36 +/- 1.14) of individuals with the CC genotype (P < 0.05). RTL (0.93 +/- 0.54) of individuals with the AT genotype at AHR rs10247158 was significantly shorter than that (1.19 +/- 0.84) of individuals with the AA genotype (P < 0.05). CONCLUSION: The results of present study suggested that PAHs exposure could induce the shorted RTL, CYP1A1, mEH, AHR polymorphisms might influence the change of telomere length of genomic DNA in peripheral blood of workers exposed to PAHs. PMID- 22096849 TI - [The effects of the cadmium chloride on the DNA damage and the expression level of gadd gene in HepG2 cell line]. AB - OBJECTIVE: To investigate the effects of the cadmium chloride on the DNA damage and the expression of the gadd153 and gadd45beta promoter and mRNA in HepG2 cells. METHODS: DNA damage induced by cadmium chloride was detected by comet assay. The plasmids (pGADD153-Luc and pG45-Luc) containing DNA damage and repair inducible gene 153 and 45 (gadd153 and gadd45beta) promoter and luciferase and gadd45beta reporter gene were constructed. The activity of gadd153 and gadd45beta promoter were represented by the luciferase activity, the inducible luciferase activities was detected by bioluminescence. The expression of gadd153 and gadd45beta mRNA was detected by RT-PCR. RESULTS: The results of comet assay indicated that Olive Tail Moment induced by the cadmium chloride increased significantly at the dose of 100, 300 micromol/L, compared with the control (P < 0.05). The luciferase activity analysis showed that the expression levels of gadd153 promoter increased significantly in 1, 5, 10 micromol/L treatment group, compared with the control (P < 0.05). The expression levels of gadd45beta promoter in 5, 10 micromol/L treatment group were significantly higher than that in control group (P < 0.05). The expression levels of gadd153 mRNA induced by cadmium chloride at the doses of 1, 5, 10 micromol/L and the expression levels of gadd45beta mRNA induced at the doses of 5, 10 micromol/L were significantly higher than thoae in control group (P < 0.05). CONCLUSION: The cadmium chloride can induce the DNA damage and increase the expression levels of the gadd153 and gadd45beta promoters in HepG2 cells. PMID- 22096850 TI - [Influence of 1, 2-dichloroethane on open field behavior and levels of neurotransmitters in brain of mice]. AB - OBJECTIVE: To explore the effects of 1,2-dichloroethane (1,2-DCE) on the behavior and the brain neurotransmitter levels in mice. METHODS: Thirty mice were randomly divided into four groups, which were control group and groups of low, middle and high exposure (225, 450 and 900 mg/m3) to 1,2-DCE for 10 days (3.5 h a day) by inhalation. After the last exposure, the open field test was performed immediately. After exposure all mice were killed and the brain tissues were taken up rapidly. The levels of aspartate (Asp), glutamate (Glu) and gamma-aminobutyric acid (GABA) in the brain were detected by high performance liquid chromatography (HPLC). RESULTS: Levels of Asp and Glu in all exposure groups increased with doses. As compared to the control group, levels of Glu in all exposure groups increased significantly (P < 0.05). Levels of GABA in the low exposure group were significantly lower than those in control group, but those in the high exposure group were significantly higher than those in control group. The results of the open field test showed that effect of low exposure to 1,2-DCE on the behavior was stimulant, but the high exposure to 1,2-DCE inhibited behavior of exploration, excitement and sport. CONCLUSIONS: Subacute exposure to 1,2-DCE could result in the change of amino acid neurotransmitter content and ratio in the brain, thereby change the behavior of mice appeared, which might be the mechanism of neurotoxicity caused by 1,2-DCE in part. PMID- 22096852 TI - [Effects of n-hexane exposure on human serum myelin basic proteins]. AB - OBJECTIVE: To explore the effects of n-hexane on expression of serum myelin proteins (MBP) in workers occupationally exposed to n-hexane. METHODS: In this study, 269 workers exposed to n-hexane for more than one year and 104 subjects not exposed to n-hexane served as the exposure group and the control group, respectively. The urinary 2,5-hexanedione levels in all subjects were detected. On the basis of urinary 2,5-hexanedione levels, the exposure group was divided into the high exposure sub-group and low exposure sub-group. The serum myelin basic protein (MBP) levels were measured by ELISA kit. RESULTS: The mean concentration of urinary 2,5-hexanedione in the exposed group was (3.10 +/- 1.35) mg/L. The concentration of urinary 2,5-hexanedione in the control group was undetectable. The levels of serum MBP in the high exposure sub-group and low exposure sub-group were (2.43 +/- 0.24) and (1.62 +/- 0.23) microg/L, respectively, which were significantly higher than that (0.78 +/- 0.12) microg/L in the controls (P < 0.01). Pearson correlation analysis showed the positive correlation between serum MBP levels and urinary 2,5-hexanedione levels (r = 0.781, P < 0.01). CONCLUSION: The results of present study showed that the serum MBP levels of workers occupationally exposed to n-hexane significantly elevated, and the serum MBP can serve as the effective biomarker of n-hexane exposure. PMID- 22096851 TI - [Effects of Xue-Bi-Jing combined with forsythia suspension on the liver gene expression levels of rats with sepsis model]. AB - OBJECTIVE: To study the effects of "XUE BI JING plus LIANQIAO" injection on gene expression levels of rats with sepsis model. METHODS: One hundred and twenty rats were randomly divided into sham operation group, sepsis model group, Te-neng group and "XUE BI JING plus forsythia suspension" group. The sepsis model of rats was prepared by "CLP" method. Tai neng group was treated by peritoneal injection Imipenem/ Cilastatin (0.18 g/kg); "XUE BI JING plus LIANQIAO" group was treated by peritoneal injection Imipenem/ Cilastatin (0.18 g/kg) plus "xue-bi-jing" (10 ml/kg) and "liang ge san" (18 g/200 g) by intragastric administration 2 times a day; the sham operation group and model group were treated by peritoneal injection of normal saline (10 ml/kg). The survival rates at 48h and 72h were observed for all groups. The gene expression levels of livers in all groups were detected by BiostarR-40s chip. The NCBI database was used to inquest Gene function and class. RESULTS: The survival rates at 48h and 72h in "XUE BI JING+ forsythia suspension" group were 83.3% and 76.7% which were significantly higher than those (30.0% and 16.7%) in sepsis model group and those (60.0% and 33.3%) in Te-neng group (P < 0.01). Model group/control group have 305 differential expression genes with 159 up-regulation genes and 146 down-regulation genes. Tai neng group/model group have 386 differential expression genes with 206 up regulation genes and 180 down-regulation genes. "XUE BI JING plus forsythia suspension" group/model group have 342 differential expression genes with 102 up regulation genes and 240 downregulation genes. The genes with up-regulation in model group/ control group and with down-regulation in"XUE BI JING plus forsythia suspension" group/model group were 24. The genes with down-regulation in the model group/ sham operation group and with up-regulation in "XUE BI JING plus forsythia suspension"group/model group were 16. CONCLUSION: "XUE BI JING plus forsythia suspension" can reduce the mortality of rats with sepsis, which could be due to the expression of relative regulation genes. PMID- 22096853 TI - [Current situation of occupational health and medicine research capability in China]. PMID- 22096854 TI - [Analysis of the mental health status of female migrant workers in electronic industry]. PMID- 22096856 TI - [Changes of brain oxidative stress induced by nano-alumina in ICR mice]. AB - OBJECTIVE: To investigate the brain oxidative stress injury induced by nano alumina particles in ICR mice. METHODS: Sixty male ICR mice were randomly divided into 6 groups: control group, solvent control group, 100 mg/kg micro-alumina particles group, 3 groups exposed to nano-alumina particles at the doses of 50, 100 and 200 mg/kg. The mice were exposed by nasal drip for 30 days. Then levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in brain tissues of mice were detected. RESULTS: There was no difference of SOD activity in mouse brain between control group [(17.32 +/- 6.23)U/gHb] and 50 mg/kg nano-alumina particles group [(17.89 +/- 1.82) U/gHb]. The SOD activity [(4.93 +/- 2.30)U/gHb] in 200 mg/kg nano alumina particles group was significantly lower than that in control group (P < 0.05). The MDA levels in 3 nano-alumina particles groups were (0.76 +/- 0.13), (1.00 +/- 0.30) and (1.16 +/- 0.39)nmol/ml, respectively, which were significantly higher than that [( 0.24 +/- 0.09)nmol/ml] in control group (P < 0.05). The GSH levels in 3 nano-alumina particles groups were (0.72 +/- 0.08), (0.55 +/- 0.19) and (0.61 +/- 0.20)mg/gpro, respectively, which were significantly lower than that [(1.55 +/- 0.34)mg/gpro]] in control group (P < 0.05). The CAT activity in 50 and 100 mg/kg nano-alumina particles groups were (10.40 +/- 3.84) and (10.40 +/- 2.00)U/mgpro, respectively, which were significantly higher than that [(5.79 +/- 0.96) U/mgpro] in control group (P < 0.05). The CAT activity [(3.25 +/- 1.04)U/mgpro] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05 ). CONCLUSION: Nano-alumina particles can induce the oxidative stress damage in brain tissues of mice. PMID- 22096855 TI - [Study on alternative methods for the acute oral toxicity in detection of chemicals]. AB - OBJECTIVE: To evaluate three alternative methods for LD50 test-Fixed Dose Procedure (FDP), the Acute Toxic Class Method (ATC) and Up and Down Procedure (UDP). METHODS: Female SD rats (8-12 weeks of age, 160-200 g) were used. Three alternative methods from OECD were applied to assess 22 chemicals (10 cosmetic raw materials and 12 raw materials of personal and home care products). The toxicity ranking for tested chemicals was established according to Globally Harmonized System (GSH). The results LD50 test were compared for the consistency and correlation between alternative methods and traditional test. RESULTS: For cosmetic raw materials, the concordance rate of the three alternative methods was 80% (8/10); for raw material of personal and home care products, the concordance rates of FDP, ATC and UDP was 91.7% (11/12), 75.0% (9/12) and 83.0% (10/12), respectively. The number of animals required in three alternative methods was significantly lower than that in traditional test (P < 0.05), but the time required in three alternative methods was significantly higher than that in traditional test (P < 0.05). CONCLUSIONS: High consistency and correlation were found between each alternative method and LD50 test. FDP may be more potential when applied to assess acute oral toxicity of cosmetic raw materials. PMID- 22096857 TI - [Effects of paraquat on the learning and memory ability in developing mice]. AB - OBJECTIVE: To explore the damages of paraquat to the learning and memory ability of developing mice and explore the possible mechanism involving oxidative stress. METHODS: Eighty healthy Kunming mice in aged 21 days were divided into 4 groups randomly: a control group (distilled water) and three paraquat treatment groups. The doses of paraquat were 0.89, 2.67 and 8mg/kg body weight, respectively. Paraquat was administered orally in doses of 0.1 ml/10 g body weight, respectively, once a day and for 28 consecutive days. The Morris water maze test and the shuttling and avoid dark box test were used to detect the learning and memory abilities of mice. The levels of MDA and the activities of SOD and GSH-PX were detected according to the commercial kits manual using a microplate reader. RESULTS: Morris water maze test showed that the escape latency of mice after paraquat treatment (57.98 +/- 2.78, 62.35 +/- 3.18, 85.57 +/- 5.10) were significantly increase compared with the control (21.74 +/- 1.36), respectively (P < 0.05). There were good dose-response relationship (R = 0.8629, P < 0.05). The shuttling and avoid dark box test showed that initiative avoidance latency of mice after paraquat treatment (5.56 +/- 0.29, 6.08 +/- 0.22, 8.32 +/- 0.38) were significantly increase compared with the control (3.50 +/- 0.13), respectively (P < 0.05). There were good dose-response relationship (R = 0.9579, P < 0.05). The levels of MDA in serum of mice in paraquat treatment groups (2.67 and 8 mg/kg) (24.76 +/- 1.76, 31.10 +/- 4.57) and in hippocampus of mice in each paraquat treatment groups were significantly increase compared with the control (serum: 16.38 +/- 6.26, hippocampus: 1.93 +/- 0.39) (P < 0.05, respectively). The activities of SOD in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum: 213.25 +/- 6.78, hippocampus: 197.36 +/- 6.37) (P < 0.05, respectively). The activities of GSH-PX in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum: 583.47 +/- 11.23, hippocampus: 412.38 +/- 13.16) (P < 0.05, respectively). CONCLUSION: Paraquat can induce the oxidative damage in hippocampus, and then influence the learning and memory abilities of developing mice. PMID- 22096858 TI - [The assessment of hemoperfusion for the treatment of acute methamidophos poisoning]. AB - OBJECTIVE: To explore the effect of hemoperfusion(HP) about the patients of methamidophos poisoning. METHODS: On the basis of comprehensive treatment,15 cases of severe acute methamidophos poisoning patients were treated with HP, Blood samples were collected at 7 time points, before and 5, 15, 30, 45, 60mins following the beginning and the end of hemoperfusion. Blood samples were used for measuring the concentration of methamidophos and perfusion devices were used for measuring the volume of methamidophos adsorbed by the device after hemoperfusion. RESULTS: 15 patients live in 12 cases, 3 cases of death. HP (former) blood Cholinesterase vigor were 662.60 + 632.05, HP (after) blood cholinesterase vigor were 2577.52 + 920.38 IU/L; The difference of blood Cholinesterase vigor between the before and after HP was statistically significant (P < 0.01). The patients' methamidophos concentration of blood when HP treated 45, 60, 120 min were respectively (851 + 672), (680 + 529), (587 + 520) microg /ml, there were significantly lower than that the patients' methamidophos concentration of blood who were before HP (1659 + 1105) microg/ml, a statistically significant difference (P < 0.01). CONCLUSION: HP can be cut down obviously methamidophos poisoning patients serum concentrations of toxic, the experimental method directly prove the clinical application of carbon HP can really adsorption methamidophos. PMID- 22096859 TI - [Acute poisoning of the clinical analysis of p-nitroaniline]. PMID- 22096860 TI - [The clinical analysis of pesticide poisoning by injection: a report of 10 case]. PMID- 22096861 TI - [Clinical report of occupational acute dimethylformamide poisoning]. PMID- 22096862 TI - [Development of determination of germanium hydride in the air of workplace by atomic fluorescence]. AB - OBJECTIVE: An atomic fluorescence (AFS) method was developed to determine germanium hydride in the air of workplace. METHOD: Germanium hydride in the air of workplace was collected by charcoal tube, and desorbed by nitric acid followed filtration with 0.22 microm cellulose filter, the AFS was used to determine Germanium in the desorbed solution. RESULTS: The linear was good at the range of 0.85-300 microg/L with the correlation coefficient of 0.9993; the LOD and LOQ were 0.51 microg/L and 0.000 17 mg/m3, respectively. The recovery was ranged from 90% to 106%, the RSD of intra- and inter- precision were 3.3%-5.9% and 3.7%-6.3%. CONCLUSION: The linear range, sensitivity and precision of the method were all satisfied for the determination of germanium hydride in the air of workplace. PMID- 22096863 TI - [Determination of diborane in the air of workplace by ICP-AES]. AB - OBJECTIVE: A sampling method was established to collect diborane in the air of workplace and an ICP-AES method was developed to determine the Boron in desorbed solution. METHOD: Diborane in the air of workplace was collected by solid sorbent tube filled with oxidant impregnated activated carbon. The adsorbed diborane was desorbed into 3% H2O2 aqueous, and then the desorbed Boron was determined by ICP AES. RESULTS: The sampling efficiency of this method was 99.6% with the desorption efficiency of diborane with 5.660 microg and 56.6 microg spiked were 90.9% and 99.5%, respectively. Both the intra-and inter-precision RSD were less than 8%. The standard curve of this method ranged from 0.1 to 10.0 microg/ml (Boron), and the LOD and LOQ were 0.011 mg/m3 and 0.035 mg/m3 (15L samples) respectively. CONCLUSION: The method established was suitable for diborane sampling and determination in the air of workplace. PMID- 22096864 TI - [Determination of four acids in the air of workplace by gas chromatography]. AB - OBJECTIVE: Four kinds of acids (acetic acid, propionic acid, acrylic acid and methylacrylic acid) in the air in a workplace were quantitatively determined by gas chromatography synchronously. METHODS: Four acids in the air were adsorbed by silica gel tube sampling and solvent desorption using acetone, then analyzed by GC with FFAP capillary column. RESULTS: To acetic acid, propionic acid, acrylic acid and methylacrylic acid, the linear regression equations were respectively y = -4.3+1.46x (r = 0.999), y = 0.4+2.37x (r = 0.999), y = 10.4+1.73x (r = 0.999) and y = -2.3+3.21x (r = 0.999). The detection limits were respectively 3.4 microg/mL, 2.1 microg/mL, 2.9 microg/mL and 1.6 microg/mL. The average desorption efficiencies were respectively 92.2%-92.8%, 94.1%-97.4%, 94.8%-95.4% and 94.1% 98.3%. The relative standard deviations were 1.1%-4.0%, 1.2%-7.8%, 0.9%-4.0% and 1.6%-4.8%. CONCLUSION: The method is suitable to determine four kinds of acids in the air in a workplace. PMID- 22096865 TI - [Capillary gas chromatography internal standard method for the determination of urinary 2,5-hexadione]. PMID- 22096866 TI - [6486 cases of medicine poisoning]. PMID- 22096867 TI - [Clinical significance on MicroScan Rapid plus series using various antibiotic resistant bacteria]. AB - MicroScan Rapid plus Neg II Series and MicroScan Rapid plus Pos Series by Siemens Healthcare Diagnostics K.K. are the panels which enable to measure identification and antimicrobial susceptibility testing quickly and we have confirmed that it is useful for detecting drug resistance bacteria. As the identification result of comparing Rapid plus series with the current panel by using 143 strains of various drug resistance bacteria, Gram positive cocci was 87. 7%, glucose fermenter was 100% and glucose non-fermenter was 77.3 in Gram negative bacilli. On the evaluation of antimicrobial susceptibility testing, Rapid plus series, in comparison with the current panel, confirmed the lower tendency of MIC value on some drugs, but it basically presented the good concordance rate. In terms of the reporting time of antimicrobial agent, non-fermenter or MRCNS reported the result as needed after 8 hours and it took a little longer time for the report of antimicrobial agent. On the other hand, 80% or higher of antimicrobial agent on panel was reported for intestinal bacteria in 4.5 hours and for MRSA in 6.5 hours. It enabled to report the testing result on the same day. Due to the results above, Rapid plus series was highly valued on the usability, such as the early detection of drug resistance bacteria and the selection of therapeutic agents. PMID- 22096868 TI - [Evaluation of measurement method of a bacterial sepsis marker, procalcitonin]. AB - Procalcitonin (PCT) is a novel biomarker for diagnosis and severity evaluation of bacterial sepsis. PCT measurement methods provided by Wako Pure Chemical Industries, Ltd. include a fully automated chemiluminescent immunoassay system SphereLight Wako and fully automated immunoanalyzer microTASWako i30 for a quantitative measurement, and immunochromatographic assay method, B R A H M S PCT Q kit. This time, basic performance of SphereLight Wako and microTASWako i30 was evaluated as quantitative determination methods for PCT. The lower limit of detection for the both methods was 0.02 ng/ml. Correlation coefficients of 0.993 to 0.997 indicated good correlation between the two methods. The both methods allow quick and easy measurement of PCT, therefore they are helpful for diagnosis and severity evaluation of bacterial sepsis. PMID- 22096869 TI - [Pediatric heart surgery in developing countries. Twenty years experience of La Chaine de L'espoir (Chain of Hope)]. AB - Because of their high incidence, cardiac disorders in children are now a public health issue. These children require multidisciplinary management, but surgery is sometimes unavoidable. The two most frequent types of cardiac disorder in children are congenital defects and rheumatic valve disease. La Chaine de l'Espoir (Chain of Hope) is present in more than 30 countries in Africa, Asia and the Middle East. Due to the socio-economic context and lack of technical resources, pediatric heart surgery has several particular characteristics in developing countries. Infants rarely undergo cardiac surgery, given the complexity of their management and particularly the need for intensive care. Another specificity is the need to limit treatment to reparatory or conservative methods. Surgery is rarely attempted in terminally ill patients. Costs must be kept to a minimum, and this is why we have optedfor local manufacture of mitral rings, led by Daniel Roux. After 20 years of practice we have found that regional hospitals are the smallest structures that can offer acceptable results in terms of patient care and professional training PMID- 22096870 TI - [Preventing complications of cardiac malformations in poor countries]. AB - Natural selection and therapeutic efficiency limit the type of cardiac malformations that/can be treated in poor countries. Most of the patients studied here are those with left-to-right shunts (arterial, atrial and, especially, ventricular), right-to-left shunts associated with a ventricular septal defect (tetralogy of Fallot) or an atrial septal defect (trilogy of Fallot), and stenosis of the pulmonary or aortic valves. Early diagnosis is crucial, but this will require a new health policy involving specially trained nurses or technicians equipped with cheap portable echo-Doppler machines to examine babies' hearts. We then analyze the follow-up and medical treatment of these common cardiac disorders and the need for "national" centers for open- and closed-heart surgery and catheterization. We feel we have achieved our training goal when a center is able to close a VSD in a 6-month-old baby with a low rate of morbidity and mortality. PMID- 22096871 TI - [Acquired childhood heart diseases in developing countries]. AB - In developing countries rheumatic valve disease is the most frequently acquired cardiac disorder observed during childhood. Any valve may be affected but the mitral valve is the predominant site. Echocardiography has a key role in the diagnosis and treatment of these disorders. Severe rheumatic valve disease carries a high risk of morbidity and mortality. Available surgical treatments include prosthetic valve replacement and conservative surgery, which is preferable when feasible. Percutaneous mitral commissurotomy is currently the treatment of choice for mitral stenosis. Preventive strategies are needed to eliminate rheumatic fever and the valve disorders it can cause. PMID- 22096872 TI - [Kidney transplantation-dedication to Rene Kuss and Jean Hamburger]. PMID- 22096873 TI - [History of medical progress in renal transplantation: a review of 3,000 consecutive kidney grafts at Bicetre-Kremlin, Bicetre University Hospital - France]. AB - Major medical progress has been made in the field of renal transplantation over the last 40 years, thanks to advances in areas such as metabolism, immunology, therapeutics, and pathology. This progress has been accompanied by important changes in French legislation that governs organ harvest and transplantation, as well as the institutions that regulate organ allocation. Patient and graft survival have both increased markedly, although long-term improvements have been somewhat offset by complications, including adverse effects of immunosuppression. On average recipients are older than in the past and some recipients are now dying from age-related comorbidities despite having functional grafts. PMID- 22096874 TI - [Surgical view of a series of 3,000 kidney transplantations]. AB - This article reviews a series of 3,000 consecutive kidney transplantations. Vascular and urinary complications occurred in respectively 7.4 % and 9.8 % of recipients. Arterial and venous thrombosis and urinary fistulas were the most serious complications. The frequency of arterial stenosis fell from 18.8 % to 8.9 % when the artery was implanted in the external rather than the internal iliac artery. The frequency of artery stenosis fell from 15.9 % to 9.5 % when the right renal vein was extended by using the transected cadaver vena cava. Urinary fistulas were an early complication, but their incidence fellfrom 6.6 % to 2.8 % with the use of JJstents. Urinary stenosis remained frequent (5.4 %) despite the use of JJstents. Surgical and endoscopic treatment of renal artery stenosis gave very similar success rates (82 %), indicating that dilation of a stenosed artery is a good option when medical treatment fails. Endourological treatment of urinary complications was successful on 64 % of fistulas and 46 % of stenoses. The results of this series and an analysis of the literature show the importance of improving the organ harvest technique and reducing the cold ischemia time, which is the main reason for delayed recovery of graft function. PMID- 22096875 TI - [Meeting the needs of families of patients in intensive care units]. AB - As patients in intensive care units (ICUs) are not always able to decide for themselves, their family must receive thorough information on the diagnosis, prognosis and available treatments (unless the patient has expressed his/her opposition). It is crucial to provide this information before requesting the family's involvement. Together, the family and ICU physicians can ensure that the patient receives the most appropriate care. Next-of-kin may either be called on to make decisions (as surrogates) or simply to offer their considered opinion. Good communication and information are a source of comfort and empowerment for the family, especially in end-of-life settings. Finally, we examine areas warrantingfurther research on the family-physician relationship in ICUs. PMID- 22096876 TI - [Psychiatric issues during and after intensive care (ICU) stays]. AB - Stays in intensive care units (ICUs) are a source of psychological and physical stress, sometimes resulting in psychological disorders that may persist after ICU discharge. ICU stressors include exhaustion, drug-induced sleep privation, intubation, pain, noise, and a disrupted light-dark cycle. Patients remember traumatic experiences, such as a fear of being killed or abandoned, nightmares, and panic attacks. Depression is frequent but difficult to detect. Psychiatric disorders such as delirium and confusion (hallucinations, agitation, stupor) occur in almost half of all ICU patients. Simple measures can reduce the risk of such disorders, including noise reduction, less intense lighting (especially at night), individual rooms, visible clocks to reduce confusion, frequent family visits, verbal contact, reassurance, and anxiolytics. Anxiety and depression are frequent after ICU stays, and may be mixed with post-traumatic stress disorder (PTSD), which can include fear, feelings of horror, helplessness, avoidance, neurovegetative symptoms, and intrusive thoughts. New techniques are being tested to prevent these disorders, such as logbooksfor families and team members to note events during and after the ICU stay, and end-of-stay psychological OK? consultations for both the patient and the family. PMID- 22096877 TI - [Burn out syndrome among critical care workers]. AB - Burnout syndrome (BOS) is a psychological state resulting from prolonged exposure to job stressors. Because intensive care units (ICUs) are characterized by a high level of work-related stress, we reviewed the available literature on BOS among ICU-healthcare workers. Recent studies suggest that severe BOS (measured with the Maslach Burnout Inventory) is present in about half of all critical care physicians and one-third of critical care nurses. Interestingly, the determinants of BOS difer between the two groups of caregivers. Intensivists with severe BOS tend to be those with a large number of working hours (number of night shifts, and time since last vacation), whereas severe BOS among ICU nurses is mainly related to ICU organization and end-of-life care policy. ICU conflicts were independent predictors of severe BOS in both groups. Recent studies also identify potential preventive measures, such as ICU working groups, better communication during end-of-life care, and prevention and management of ICU conflicts. PMID- 22096879 TI - US death rates from myeloproliferative neoplasms, and implications for cancer surveillance. AB - Myeloproliferative neoplasms (MPN) may contribute to death from other causes due to complications and sequelae of MPN or its treatment. The present study found that the US death rate for MPN (polycythemia vera, essential thrombocythemia/thrombocytosis, and "chronic myeloproliferative disease") in 2005 2006 was twice as high using all causes of the death on the death certificate (6,488 deaths, age-standardized rate 1.06 per 100,000 per year) vs only the underlying cause (3,303 deaths, age-standardized rate 0.54 per 100,000 per year). This finding was consistent by age, gender, race (African American/black and white) and Hispanic ethnicity. Thus, surveillance of trends in MPN-related mortality rates in the population needs to take into account all causes of death on the death certificate, because MPN contributes to death from other causes such as thrombosis. MPN is a major cause of splanchnic vein thrombosis (SVT), and under-ascertainment of MPN-related deaths was suggested by the small proportion (3%) of all 848 US deaths in 2005-2006 with SVT coded as any cause of death that also had MPN coded. Increased clinical testing of peripheral blood for specific acquired genetic mutations, known since 2005 as being common in certain MPN and also in SVT, could lead to increased numbers of deaths certified as MPN-related and also incident cases of MPN reported to central cancer registries. PMID- 22096878 TI - Quality of cancer registry data: findings from CDC-NPCR's Breast and Prostate Cancer Data Quality and Patterns of Care Study. AB - BACKGROUND: The Breast and Prostate Cancer Data Quality and Patterns of Care (POC BP) Study enabled a reabstraction study of the quality of population-based, central cancer registry data on the characteristics and initial treatment of breast cancer in females and prostate cancer in the United States. METHODS: Stratified random samples of 9,103 female breast cancers and 8,995 prostate cancers were available for the analysis, using the independently reabstracted data as the gold standard to compute measurements of agreement. RESULTS: A slight majority (53% [8/15]) of the cancer site and treatment combinations showed kappa statistics > or = 0.60 and percent agreements, sensitivities, and predictive values positive > or = 80%: surgery and radiation for the 2 cancers, radiation completed and chemotherapy for breast cancer, and radiation modality and hormone therapy for prostate cancer. The qualities of the Collaborative Stage (CS) site specific factors and derived variables for the 2 cancers were inconsistent, which confirmed the need to evaluate the recently-implemented CS algorithm. CONCLUSION: The data quality analysis from POC-BP underscores the importance of examining the quality of specific data variables by cancer site, thereby highlighting those variables for which data collection procedures could be improved. PMID- 22096880 TI - Analyzing quality of colorectal cancer care through registry statistics: a small community hospital example. AB - As the quantity of elderly Americans requiring oncologic care grows, and as cancer treatment and medicine become more advanced, assessing quality of cancer care becomes a necessary and advantageous practice for any facility.' Such analysis is especially practical in small community hospitals, which may not have the resources of their larger academic counterparts to ensure that the care being provided is current and competitive in terms of both technique and outcome. This study is a comparison of the colorectal cancer care at one such center, Falmouth Community Hospital (FCH)--located in Falmouth, Massachusetts, about an hour and a half away from the nearest metropolitan center--to the care provided at a major nearby Boston Tertiary Center (BTC) and at teaching and research facilities across New England and the United States. The metrics used to measure performance encompass both outcome (survival rate data) as well as technique, including quality of surgery (number of lymph nodes removed) and the administration of adjuvant treatments, chemotherapy, and radiation therapy, as per national guidelines. All data for comparison between FCH and BTC were culled from those hospitals' tumor registries. Data for the comparison between FCH and national tertiary/referral centers were taken from the American College of Surgeons' Commission on Cancer, namely National Cancer Data Base (NCDB) statistics, Hospital Benchmark Reports and Practice Profile Reports. The results showed that, while patients at FCH were diagnosed at both a higher age and at a more advanced stage of colorectal cancer than their BTC counterparts, FCH stands up favorably to BTC and other large centers in terms of the metrics referenced above. Quality assessment such as the analysis conducted here can be used at other community facilities to spotlight, and ultimately eliminate, deficiencies in cancer programs. PMID- 22096881 TI - Textbook development at the National Cancer Registrars Association (NCRA). PMID- 22096882 TI - The national transition from ICD-9 to ICD-10. PMID- 22096883 TI - Interactive learning tool: site-specific schema crossword puzzles. AB - Staying abreast of the TNM and Collaborative Staging updates can be overwhelming. Reading voluminous amounts of study material may be the last task on a to-do list for the busy cancer registrar. Crossword puzzles can provide an alternative, interesting learning tool to support continuing education. Researching puzzle clue answers serves as an interactive approach. Puzzles included in this article are considered "informal" as their layout is not symmetrical, but the learning value is not adversely affected. Try them out and see what you know, or don't know. It can be fun! PMID- 22096884 TI - Raising the bar: sprints or marathons? PMID- 22096885 TI - [Advances in the studies of viral hepatitis and future prospectives]. PMID- 22096886 TI - [The strategy for hepatitis control in Japan]. PMID- 22096887 TI - [Hepatitis C virus infection in japan--epidemiology]. PMID- 22096888 TI - [Natural course of hepatitis C]. PMID- 22096889 TI - [Progress and perspective in HCV research]. PMID- 22096890 TI - [The origin and evolution of hepatitis C virus]. PMID- 22096891 TI - [Gene organization of hepatitis C virus and its function]. PMID- 22096892 TI - [Entry mechanisms of HCV]. PMID- 22096893 TI - [Mechanism of hepatitis C virus (HCV) RNA replication and HCV genetic variability]. PMID- 22096894 TI - [Critical roles of lipids in the HCV life cycle]. PMID- 22096895 TI - [Mechanism of HCV-associated hepatocarcinogenesis]. PMID- 22096896 TI - [Hepatitis C virus culture and its application]. PMID- 22096897 TI - [HCV replication animal model]. PMID- 22096898 TI - [Genome-wide association study and clinical application]. PMID- 22096899 TI - [Immunopathogenesis of HCV infection]. PMID- 22096900 TI - [Mechanism of HCV persistence]. PMID- 22096901 TI - [The pathogenesis of hepatitis C virus induced by viral proteins]. PMID- 22096902 TI - [Functions of host factors regarding HCV pathogenicity]. PMID- 22096903 TI - [Clinical significance for serological markers of hepatitis virus C]. PMID- 22096904 TI - [Present status of transfusion-associated hepatitis C virus infection and efficiency after implementation of nucleic acid amplification testing]. PMID- 22096905 TI - [Mother-to-infant transmission and intrafamilial transmission of hepatitis C virus]. PMID- 22096906 TI - [In-hospital HCV infection and the countermeasures]. PMID- 22096907 TI - [Hepatitis C virus infection and insulin resistance]. PMID- 22096908 TI - [HCV infection and lipid abnormalities]. PMID- 22096909 TI - [HCV infection and iron dysmetabolism]. PMID- 22096910 TI - [HCV and oxidative stress]. PMID- 22096911 TI - [Treatment for chronic hepatitis with normal serum ALT]. PMID- 22096912 TI - [Epidemiology, diagnosis and treatment for acute hepatitis C in Japan]. PMID- 22096913 TI - [Pathology of chronic viral hepatitis C]. PMID- 22096914 TI - [Development of anti viral therapy for chronic hepatitis type C]. PMID- 22096915 TI - [Treatment strategy for chronic hepatitis C in Japan]. PMID- 22096916 TI - [Indication of monotherapy with pegylated interferon or interferon for patient with HCV in Japan]. PMID- 22096917 TI - [Combination therapy of PEG-interferon and ribavirin for chronic hepatitis C in Japan]. PMID- 22096918 TI - [Improved virologic response in chronic hepatitis C treated with peginterferon, ribavirin and add-on drug]. PMID- 22096919 TI - [Splenectomy before antiviral therapy for patients with chronic hepatitis C with thrombocytopenia]. PMID- 22096920 TI - [Virus removal and eradication by double filtration plasmapheresis (DFPP)]. PMID- 22096921 TI - [Re-treatment for patients with chronic hepatitis C who previously failed to peginterferon/ribavirin therapy]. PMID- 22096922 TI - [Side effects of interferon-based therapy for chronic hepatitis C virus infection and clinical management of them]. PMID- 22096923 TI - [Treatment of elderly patients with chronic hepatitis C]. PMID- 22096924 TI - [Relation of IL28B gene polymorphism to chronic hepatitis C]. PMID- 22096925 TI - [Response to interferon therapy using mutations in the HCV-NS5A]. PMID- 22096926 TI - [Core amino acid substitutions of hepatitis C virus]. PMID- 22096927 TI - [Prediction of response to peginterferon and ribavirin therapy for chronic hepatitis C analyzed by data mining method]. PMID- 22096928 TI - [Alternative therapies for hepatitis C: UDCA and SNMC]. PMID- 22096929 TI - [Iron reduction therapy by phlebotomy for chronic hepatitis C]. PMID- 22096930 TI - [Efficacy of the NS3-4A protease inhibitor telaprevir in patients with chronic hepatitis C]. PMID- 22096931 TI - [New antivirals against hepatitis C virus(protease inhibitors, polymerase inhibitors, and host factor targeting antivirals)]. PMID- 22096932 TI - [Present management on HCV infected hemodialyzed patients]. PMID- 22096933 TI - [Coinfection of HIV with HCV]. PMID- 22096934 TI - [Management of hepatitis C recurrence after liver transplantation]. PMID- 22096935 TI - [Extrahepatic manifestation associated with infection of hepatitis C virus and its management]. PMID- 22096936 TI - [Development of hepatocellular carcinoma from chronic hepatitis C]. PMID- 22096937 TI - [Antiviral treatment reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related chronic hepatitis and cirrhosis]. PMID- 22096938 TI - [Effects of interferon treatment on recurrence and survival after curative treatment of hepatitis C virus-related hepatocellular carcinoma]. PMID- 22096939 TI - [Hepatitis B virus infection in Japan--epidemiology]. PMID- 22096940 TI - [Natural history of hepatitis B virus infection]. PMID- 22096941 TI - [Progress and perspective in HBV research]. PMID- 22096942 TI - [Structure and replication mechanisms of hepatitis B virus]. PMID- 22096943 TI - [Hepatitis B virus genotype and the mutation related to clinical outcome]. PMID- 22096944 TI - [Hepatocarcinogenesis by HBV]. PMID- 22096945 TI - [Hepatitis B virus (HBV) replication in animal models and their applications]. PMID- 22096946 TI - [Mechanisms of the immune response against HBV infection]. PMID- 22096947 TI - [The mechanisms of establishment of chronic infection of HBV]. PMID- 22096948 TI - [The mechanisms and clinical significance of seroconversion of HBsAg to anti HBs]. PMID- 22096949 TI - [Markers of hepatitis B virus and clinical significances]. PMID- 22096950 TI - [Prevention of mother-to-child and intrafamilial transmission in hepatitis B virus infection]. PMID- 22096951 TI - [The present situation of hepatitis B virus infection as a sexual transmitted disease in Japan]. PMID- 22096952 TI - [Protection from HBV infection in medical institution]. PMID- 22096953 TI - [Indications and efficacy of hepatitis B vaccines (HB vaccines) and hepatitis B immune globulin (HBIG): current situations and problems of hepatitis B virus (HBV) infection-preventing strategies in Japan]. PMID- 22096954 TI - [Mechanisms of liver injury and viral regulation in hepatitis B]. PMID- 22096955 TI - [Clinical implication of hepatitis B virus genotype]. PMID- 22096956 TI - [HBeAg and HBV DNA in chronic hepatitis B]. PMID- 22096957 TI - [The clinical features of HBV asymptomatic carrier, and management]. PMID- 22096958 TI - [Epidemiology, diagnosis and treatment for acute hepatitis B]. PMID- 22096959 TI - [Demographic and clinical features, diagnosis and treatment of fulminant hepatitis induced by HBV infection in Japan]. PMID- 22096960 TI - [Current status of chronic hepatitis B]. PMID- 22096961 TI - [Pathology of chronic hepatitis B]. PMID- 22096962 TI - [The factors associated with pathology, treatment and prognosis of chronic hepatitis B]. PMID- 22096963 TI - [The past, present and future treatment for chronic hepatitis B]. PMID- 22096964 TI - [Treatment strategy for chronic hepatitis B in Japan]. PMID- 22096966 TI - [Entecavir]. PMID- 22096965 TI - [Interferon therapy for chronic hepatitis B]. PMID- 22096967 TI - [Lamivudine, adefovir dipivoxil]. PMID- 22096968 TI - [Sequential therapy for chronic hepatitis B]. PMID- 22096969 TI - [Immunotherapy for chronic hepatitis due to HBV]. PMID- 22096970 TI - [Treatment of difficult-to-treat chronic hepatitis B]. PMID- 22096971 TI - [New drugs of treatment of patients with chronic hepatitis B]. PMID- 22096972 TI - [Occult HBV infection]. PMID- 22096973 TI - [Prevention and management of hepatitis B virus reactivation during anticancer or immunosuppressive therapy]. PMID- 22096974 TI - [Prophylaxis of hepatitis B viral re-infection after liver transplantation]. PMID- 22096975 TI - [Management of HIV and HBV co-infection]. PMID- 22096976 TI - [Hepatitis B virus associated chronic liver diseases and carcinogenesis]. PMID- 22096977 TI - [Prevention for the development of hepatitis B virus-related hepatocellular carcinoma by anti-viral treatment]. PMID- 22096978 TI - [Efficacy of adjuvant treatment after curative treatment in patients with HBV related hepatocellular carcinoma]. PMID- 22096979 TI - [Epidemiology and recent feature of hepatitis A in Japan]. PMID- 22096980 TI - [Virological and molecular characteristics of hepatitis A virus]. PMID- 22096981 TI - [Recent clinical characteristics of hepatitis A]. PMID- 22096982 TI - [Epidemiology and recent trend of hepatitis E in Japan]. PMID- 22096983 TI - [Virological characteristics of hepatitis E virus]. PMID- 22096984 TI - [Hepatitis E, diagnosis and treatment]. PMID- 22096985 TI - [Hepatitis D--overview]. PMID- 22096986 TI - [Molecular mechanisms regulating the activity of macrophages]. AB - This article reviews modern concepts of the most common types of macrophage activation: classical, alternative, and type II. Molecular mechanisms of induction and regulation of these three types of activation are discussed. Any population of macrophages was shown to change its properties depending on its microenvironment and concrete biological situation (the "functional plasticity of macrophages"). Many intermediate states of macrophages were described along with the most pronounced and well-known activation types (classical activation, alternative activation, and type II activation). These intermediate states are characterized by a variety of combinations of their biological properties, including elements of the three afore mentioned types of activation. Macrophage activity is regulated by a complex network of interrelated cascade mechanisms. PMID- 22096987 TI - [Immunobiological properties of Yersinia pestis antigens]. AB - The present review contains information concerning immunobiological properties of plague microbe antigens. All of the identified antigens are evaluated in relation to pathogenicity of Yersinia pestis namely a resistance to phagocytosis, toxicity, adhesiveness etc. as well as persistence ability and adaptation to variable environment. In addition, the role of antigens in immunogenicity of living plague microbe for experimental animals is considered. The data concerning mechanisms of antigenic contribution to the development of adaptive immunity are presented. PMID- 22096988 TI - [Synthesis of biosynthetic precursors of red fluorescent proteins' chromophores]. AB - A method for the synthesis of 5-arylidene-3,5-dihydro-4H-imidazol-4-ones, the corresponding chromophore of green fluorescent protein (GFP) with acylaminoalkyl substituents at position 2 of imidazole core have been developed. These structures represent biosynthetic precursors of the chromophores of red fluorescent proteins. The method is based on masking of the dehydrotyrosine fragment with beta-hydroxytyrosine moiety The key stages of the synthesis include peptide coupling of beta-hydroxytyrosine with the N-acetylamino acid of choice, unmasking of dehydrotyrosine by O-acylation with subsequent elimination, and cyclization of the obtained derivatives of 3-acylaminocinnamic acid in basic media. PMID- 22096989 TI - [Proteolysis of semax analogues with different N-terminal amino acids by aminopeptidases]. AB - Proteolysis of semax (Met-Glu-His-Phe-Pro-Gly-Pro, Sem) and its analogues ([Ala1]Sem, [Gly1]Sem, [Thr1]Sem, [Trp1]Sem) that are differ from semax in substitution of N-terminal Met residue were studied. It is shown that such replacement changes the rate of peptides degradation by N-aminopeptidases (EC 3.4.11.2, Sigma, Type VI, 9.2 units. Akt. / mg). [Ala1]Sem, [Gly1]Sem and [Thr1]Sem semax analogues proved to be more stable to proteolysis than semax (Sem), and their initial product of proteolysis is His-Phe-Pro-Gly-Pro (Sem-5). For triptophan analogue both Glu-His-Phe-Pro-Gly-Pro (Sem-6) and Sem-5 product are formed in similar quantities. It is found that all investigated analogues can be used as inhibitors in Sem proteolysis. PMID- 22096990 TI - Antimicrobial activity of marine sponge Clathria indica (Dendy, 1889). AB - Sponges are sessile filter feeders that have developed efficient defense mechanisms against foreign invaders such as viruses, bacteria or eukaryotic organisms. Antimicrobial peptides are known as major components of the innate immune defense system in marine invertebrates. The aim of the present work was to study the antimicrobial properties of the Indian sponge Clathria indica with special reference to the identification of antimicrobial peptides. Crude methanolic extract and its chloroform, n-butanol and aqueous fractions were tested against 16 human pathogens which include eleven bacteria with four of them being multidrug resistant and five pathogenic fungi. All fractions showed effective antibacterial activity against common and multidrug-resistant Salmonella typhi and antifungal activity against C. albicans and C. neoformans. However, they were ineffective against Escherichia coli, Pseudomonas aeruginosa, Streptococcus pyogenes and Staphylococcus aureus. Chloroform fraction being the most potent among the fractions tested on chemical investigation was indicative of the presence of peptides as evidenced by ninhydrin positive spots on TLC and presence of peptide bonds by NMR. Its ESI-MS showed presence of several peptides in the range of m/z 850 to 980. Structure of three peptides has been tentatively assigned by ESI-MS/MS or tandem mass analysis, on the basis of the amino acid sequence established. The results clearly show that the sponge C. indica represent an interesting source of marine invertebrates-derived antimicrobial peptides in the development of new strategies to treat various infectious diseases. PMID- 22096991 TI - [Cloning, expression, isolation and properties of thymidine kinase herpes simplex virus, strain L2]. AB - A thymidine kinase UL23 gene (EC 2.7.1.145) from an acyclovir-sensitive strain L2 of herpes simplex virus type 1 was cloned and expressed in E. coli. Enzyme was purified by chromatography to a homogeneous state controlled by PAG electrophoresis. The Michaelis constants for the reactions with thymidine and an acyclovir were determined. It was found that enzyme phosphorilate some modified nucleosides such as d2T, d4T, d2C, 3TC, FLT, BVDU, GCV. A comparison of the purified enzyme properties and properties ofthymidine kinase of other strains of herpes simplex virus, previously published was carried out. It is shown that enzyme is inhibited by acyclovir H-phosphonate. PMID- 22096992 TI - [A new method of producing biologically active nanocomplexes by non-covalent conjugation of proteins with viral particles]. AB - Currently, a range of biologically active molecules have been attached to plant and bacterial viras nanoscaffolds, yielding stable nanoparticles that display multiple copies of the desired molecule. In this paper we propose a new method of non-covalent attachment of peptides to the surface of virios. We have demonstrated that this method is efficient in a model system that includes tobacco mosaic virus particles, synthetic polycation (quaternized poly(4 vinylpyridine) carrying ethyl ethyl pendant radicals) and polypeptide of interest. This principle of step-by-step binding to the surface of virions was used for electrostatic association with hydrophilic fragment of influenza virus haemagglutinin. PMID- 22096993 TI - [Changing the protective properties of the receptor domain of protective antigen anthrax exotoxin, depending on the orientation of the presentation on nanoparticles]. AB - Polysterene particles bearing on its surface recombinant protein receptor domain of protective antigen anthrax exotoxin, exposed in different orientations have been constructed. Particles with exposed COOH region of receptor domain induced the highest protective immunity in mice anthrax model (95%). We revealed that immunization with these particles causes a specific induction of Th1-response, characterized by increased levels ofcytokine TNF-alpha and IL-2. PMID- 22096994 TI - [Myeloperoxidase-induced biodegradation of single-walled carbon nanotubes is mediated by hypochlorite]. AB - Broad prospects for the use of single-walled carbon nanotubes (SWNTs) in medicine and biotechnology raise the concerns about both their toxicity, and the mechanisms of biodegradation and excretion from the body. SWNTs biodegradation as a result of catalytic activity of myeloperoxidase (MPO) was shown in the isolated MPO system as well as in the suspension of neutrophils [Kagan V.E., et al., 2010]. In the present study we analyzed the ability of different MPO-produced oxidants to participate in the modification and degradation of SWNTs. The comparison of the ability of various peroxidases to degrade SWNTs in vitro revealed that myeloperoxidase, due to its ability to produce hypochlorite, and lactoperoxidase, due to its ability to produce hypobromite, are extremely efficient in the degradation of carbon nanotubes. The biodegradation of SWNTs in the model system can also be caused by free radicals generated as a result of heme degradation and, to a lesser extent, by active oxoferryl intermediates of peroxidases. Our experiments showed that in the presence of blood plasma, peroxidase intermediates or free radical products of heme degradation were unable to initiate biodegradation of carbon nanotubes, only the generation of hypochlorite by MPO can cause the biodegradation of carbon nanotubes in vivo. Titration of SWNTs suspension containing plasma with hypochlorite at high concentrations resulted in the decrease in the optical absorbance of the suspension indicating the degradation of nanotubes. Our results clearly indicate that hypochlorite can serve as a main oxidizing agent which is able to modify and degrade nanotubes in the sites of inflammation and in the phagosomes. PMID- 22096995 TI - [Application of the duplex-specific nuclease for fast analysis of single nucleotide polymorphisms and detection of target DNA in complex PCR products]. AB - We have developed a simple method for fast analysis of single nucleotide polymorphisms and identification of target clones from cloned complex PCR products. The method utilizes Kamchatka crab duplex-specific nuclease and universal fluorescent probe and is alternative to laborious screening procedures using radioactive probes, restriction analysis followed by gel electrophoresis or expensive sequencing. The method efficacy was demonstrated in several model experiments. PMID- 22096996 TI - [DNA sequence-specific ligands: XIV. Synthesis of fluorescent biologicaly active dimeric bisbenzimidazoles-DB(3, 4, 5, 7, 11)]. AB - Five fluorescent symmetric dimeric bisbenzimidazoles DB(n) have been synthesized containing four 2,6-substited benzimidazole fragments and differ in length of oligomethylene linker (n=3, 4, 5, 7, 11) between the two bisbenzimidazole blocks. The ability of these dimeric bisbenzimidazoles to form complexes with double stranded DNA (dsDNA) was shown by spectral methods. Upon binding to dsDNA DB(n) are localized in the minor groove. The DNA-methyltransferase Dnmt3a inhibition data are demonstrate the site-specific binding of dimeric bisbenzimidazoles DB(3) and DB(11) with oligonucleotide duplex. PMID- 22096997 TI - [Synthesis and antituberculosis activity of the derivatives of glycoside steviolbioside from the plant Stevia rebaudiana and diterpenoid isosteviol containing hydrazone, hydrazide and pyridinoyl moieties]. AB - Conjugates of antitubercular drug Isoniazid (hydrazide of isonicotinic acid), nicotinic and alpha-picolinic acid hydrazides and glycoside steviolbioside from the plant Stevia rebaudiana as well as the product of its acid hydrolysis, diterpenoid isosteviol, were synthesized. Besides, isosteviol hydrazide and hydrazone derivatives as well as conjugates containing two isosteviol moieties connected by dihydrazide linker were also obtained. Both initial compounds and their synthetic derivatives inhibit the growth of Mycobacterium tuberculosis (H37Rv in vitro). The minimum concentration at which the growth of M. tuberculosis was inhibited by 100% (MIC) for stevioside and steviolbioside equals 7.5 and 3.8 microg/mL, respectively. MIC values for conjugates of the hydrazides of pyridine carbonic acids and steviolbioside as well as isosteviol are in the ranges 5-10 and 10-20 microg/mL, respectively. Maximum inhibitory effect against M. tuberculosis showed the conjugates of isosteviol and adipic acid dihydrazide (MIC values ranged from 1.7 to 3.1 microg/mL). Antitubercular activity of the compounds studied is higher than the activity of antitubercular drug Pyrizanamide (MIC = 12.5-20 microg/mL) but lower than the activity of antitubercular drug Isoniazid (MIC = 0.02-0.04 microg/mL). PMID- 22096998 TI - [Synthesis of cationic ether glycerolipids with heterocyclic nitrogen containing bases as polar domains]. AB - Synthesis of new antitumor ether glycerolipids with various heterocyclic nitrogen containing bases as polar domains is described. We propose synthetic scheme for cationic lipids containing aliphatic short-chain substituents in the heterocyclic polar head. PMID- 22096999 TI - [Two new asterosaponins from the antarctic starfish Diplasterias brucei. Structures and cytotoxic activities]. AB - Two new asterosaponins, diplasteriosides A and B, with the same oligosaccharide chains beta-D-Fucp-(1-->2)-beta-D-Galp-(1-->4)-[beta-D-Quip-(1-->2)]-beta-D-Quip (1-->3)-beta-D-Quip-(1-->, linked to C6 of known genins, 3-O-sulfates of thornasterols A and B, respectively, were isolated along with the previously known asteriidoside A from the Antarctic starfish Diplasterias brucei. The structures of new compounds were elucidated by spectroscopic methods (mainly 2D NMR and mass spectrometry). The cytotoxicity of isolated asterosaponins against human colon cancer cell line HCT-116, human breast cancer cell line T-47D, and human melanoma cancer cell line RPMI-7951 was investigated. PMID- 22097000 TI - [Synthesis of amino analogues of cholic acid]. AB - Amino analogues of cholic acid were synthesized by reduction of oximes with combination of titanium(III) chloride and sodium cyanoborohydride. PMID- 22097001 TI - Characterisation of the recalcitrant organic compounds in leachates formed during the anaerobic biodegradation of waste. AB - This study investigates the use of UV absorption and fluorescence spectroscopy to assess the early development of recalcitrant organic compounds in leachates formed during the anaerobic biodegradation of municipal solid waste. Biochemical methane potential tests were carried out on fresh waste (FW) and composted waste (CW) over a period of 150 days and leachates produced from the degradation of two wastes were analysed for humic-like (H-L) and fulvic-like (F-L) structures by UV spectroscopy and fluorescence excitation-emission-matrix analyses. During anaerobic biodegradation, the synthesis and utilization of H-L and F-L structures in the leachates over time was indicative of the generation of the recalcitrant organic compounds. The results obtained from UV absorption and fluorescence spectroscopy suggested that CW leachates resulted in a higher concentration and more condensed form of recalcitrant H-L and F-L molecules than FW leachates. These findings demonstrate how fluorescence and UV absorption spectroscopy can be used as an indicator for monitoring the evolution of recalcitrant organic compounds (H-L and F-L substances) in leachates formed at different stages of waste biodegradation. PMID- 22097002 TI - The feasibility of trace element supplementation for stable operation of wheat stillage-fed biogas tank reactors. AB - The aim of this study was to investigate the effect of trace element supplementation on operation of wheat stillage-fed biogas tank reactors. The stillage used was a residue from bio-ethanol production, containing high levels of sulfate. In biogas production, high sulfate content has been associated with poor process stability in terms of low methane production and accumulation of process intermediates. However, the results of the present study show that this problem can be overcome by trace element supplementations. Four lab-scale wheat stillage-fed biogas tank reactors were operated for 345 days at a hydraulic retention time of 20 days (37 degrees C). It was concluded that daily supplementation with Co (0.5 mg L(-1)), Ni (0.2 mg L(-1)) and Fe (0.5 g L(-1)) were required for maintaining process stability at the organic loading rate of 4.0 g volatile solids L(-1) day(-1). PMID- 22097003 TI - Evaluation of cattle bedding and grazing BMPs in an agricultural watershed in Alberta. AB - This paper highlights the environmental impacts of implementing beneficial management practices to address cattle bedding and direct access to the creek in a study watershed in southern Alberta, Canada. Approximately 35 cow-calf pairs grazed 194 ha of grass forage and had direct access to the creek in the spring and summer. During winter, the cattle were fed adjacent to the creek at an old bedding site. The practice changes included off-stream watering, bedding site relocation and fencing for rotational grazing. The cost was $15,225 and 60 h of labour. Four years of data were used in a before-and-after experimental design to evaluate the practice changes. After two years of post-implementation monitoring, riparian assessments showed an increase in plant diversity, but no change in the percent cover of the riparian species Salix exigua and Juncus balitus and a decrease in Carex sp. (P < 0.05). Water quality monitoring showed a decrease in the difference between upstream and downstream concentrations of total phosphorus, total dissolved phosphorus, total nitrogen, organic nitrogen and Escherichia coli (P < 0.10). These results showed that improved environmental changes in riparian and water quality can be measured following the implementation of beneficial management practices for cattle bedding and grazing. PMID- 22097004 TI - Recovering phosphorus as struvite from the digested swine wastewater with bittern as a magnesium source. AB - Recovering nitrogen and phosphorus through struvite (MgNH4PO4 6H2O) crystallization from swine wastewater has gained increasing interest. However, swine wastewater contains complex compositions, which may hinder the formation of struvite crystal and affect the purity of the precipitates by forming other insoluble minerals. In this work, experiments were carried out to evaluate struvite precipitation in the anaerobically digested swine wastewater, with dosing bittern as a low-cost magnesium source. Exceeded 90% phosphate removal and 23-29% ammonium reduction were obtained. FTIR, XRD and mass balance analysis were combined to analyze the species of precipitated minerals. Results showed that the precipitates were struvite, mixed with amorphous calcium phosphate (ACP) and brucite. The presence of Ca2+ diminished the percentage of struvite and gave rise to ACP formation. Controlling pH below 9.5 and bittern dosage above 1% (w/w) could inhibit ACP precipitation and harvest a highly pure struvite crystal product. PMID- 22097005 TI - Effect of xylose and nutrients concentration on ethanol production by a newly isolated extreme thermophilic bacterium. AB - An extreme thermophilic ethanol-producing strain was isolated from an ethanol high-yielding mixed culture, originally isolated from a hydrogen producing reactor operated at 70 degrees C. Ethanol yields were assessed with increasing concentrations of xylose, up to 20 g/l. The ability of the strain to grow without nutrient addition (yeast extract, peptone and vitamins) was also assessed. The maximum ethanol yield achieved was 1.28 mol ethanol/mol xylose consumed (77% of the theoretical yield), at 2 g/l of initial xylose concentration. The isolate was able to grow and produce ethanol as the main fermentation product under most of the conditions tested, including in media lacking vitamins, peptone and yeast extract. The results indicate that this new organism is a promising candidate for the development of a second generation bio-ethanol production process. PMID- 22097006 TI - A sewer process model as planning and management tool--hydrogen sulfide simulation at catchment scale. AB - The collection system of a major city at the Persian Gulf was simulated for bulk water hydrogen sulfide and the release of sewer gas to the urban atmosphere. Geometry data on 870 km of sanitary sewer and data on dry weather flow entering all nodes in the catchment was exported from a Mike Urban database and imported to the sewer process model WATS. The process model then routed sewage and sewer gas through the system and simulated relevant physical, chemical and biological processes. In its non-calibrated state, the model was used as a planning tool to identify problem areas and to identify locations to install monitoring equipment and make preliminary choices for control strategies in terms of dosing of nitrate and iron salts. The monitoring equipment consisted of flow meters, level gauges, UV-Vis spectroscopes, and H2S gas sensors. Data from the first set of installed monitoring equipment were applied to calibrate and validate the model. It was illustrated how the calibrated model can be applied to assess compliance with quantitative formulated service levels and to design control strategies in terms of dosing of iron and nitrate salts. PMID- 22097007 TI - Pulse shear stress for anaerobic membrane bioreactor fouling control. AB - Increase of shear stress at membrane surfaces is a generally applied strategy to minimize membrane fouling. It has been reported that a two-phase flow, better known as slug flow, is an effective way to increase shear stress. Hence, slug flow was introduced into an anaerobic membrane bioreactor for membrane fouling control. Anaerobic suspended sludge was cultured in an anaerobic membrane bioreactor (AMBR) operated with a side stream inside-out tubular membrane unit applying sustainable flux flow regimes. The averaged particle diameter decreased from 20 to 5 microm during operation of the AMBR. However, the COD removal efficiency did not show any significant deterioration, whereas the specific methanogenic activity (SMA) increased from 0.16 to 0.41 gCOD/g VSS/day. Nevertheless, the imposed gas slug appeared to be insufficient for adequate fouling control, resulting in rapidly increasing trans membrane pressures (TMP) operating at a flux exceeding 16 L/m2/h. Addition of powdered activated carbon (PAC) enhanced the effect of slug flow on membrane fouling. However, the combined effect was still considered as not being significant. The tubular membrane was subsequently equipped with inert inserts for creating a locally increased shear stress for enhanced fouling control. Results show an increase in the membrane flux from 16 L/m2/h to 34 L/m2/h after the inserts were mounted in the membrane tube. PMID- 22097008 TI - Dewatering sludge originating in water treatment works in reed bed systems. AB - The dewatering process of the liquid water works sludge was examined in a trial with a series of six trial beds, each 20 m2. These were monitored from April 2008 to June 2010. It is possible to get the vegetation to grow in ferric sludge (approximately 300,000 mg Fe/kg dry solid, pH 7,7). It has not been necessary to use fertilizer. The influence of the loading programs (15-50 kg dry solid/m2/year) was tested with 1-5 days of loading and 35-55 days of rest. It is possible to drain and treat ferric sludge. Generally the dewatering profile is a peak with a maximum over 0.015-0.025 L/s/m2. The times for dewatering of 6-12 m3 are approximately 15 h and over 90% of the load is dewatered in that period. The dry solid (0.16-0.20%) in the sludge has been concentrated approximately 200 times. The dewatering phase results in ferric sludge with 30-40% dry solid which cracks up very quickly. The volume reduction is over 99%. The trend shows that the main volume of reject water has a turbidity level below 5 NTU even in the loading periods. PMID- 22097009 TI - Continuous hydrogen and methane production in a two-stage cheese whey fermentation system. AB - The feasibility of integrating biological hydrogen and methane production in a two-stage process using mixed cultures and cheese whey powder (CWP) as substrate was studied. The effect of operational parameters such as hydraulic retention time (HRT) and organic loading rate (OLR) on the volumetric hydrogen (VHPR) and methane (VMPR) production rates was assessed. The highest VHPR was 28 L H2/L/d, obtained during stable operation in a CSTR at HRT and OLR of 6 h and 142 g lactose/ L/d, respectively. Moreover, hydrogen (13 L/L/d) was produced even at HRT as low as 3.5 h and OLR of 163 g lactose/L/d, nonetheless, the reactor operation was not stable. Regarding methane production in an UASB reactor, the acidified effluent from the hydrogen-producing bioreactor was efficiently treated obtaining COD removals above 90% at OLR and HRT of 20 g COD/L/d and 6 h, respectively. The two-stage process for continuous production of hydrogen and methane recovered over 70% of the energy present in the substrate. This study demonstrated that hydrogen production can be efficiently coupled to methane production in a two-stage system and that CWP is an adequate substrate for energy production. PMID- 22097010 TI - Enhancement of the conventional anaerobic digestion of sludge: comparison of four different strategies. AB - Anaerobic digestion (AD) is the preferred option to stabilize sludge. However, the rate limiting step of solids hydrolysis makes it worth modifing the conventional mesophilic AD in order to increase the performance of the digester. The main strategies are to introduce a hydrolysis pre-treatment, or to modify the digestion temperature. Among the different pre-treatment alternatives, the thermal hydrolysis (TH) at 170 degrees C for 30 min, and the ultrasounds pre treatment (US) at 30 kJ/kg TS were selected for the research, while for the non conventional anaerobic digestion, the thermophilic (TAD) and the two-stage temperature phased AD (TPAD) were considered. Four pilot plants were operated, with the same configuration and size of anaerobic digester (200 L, continuously fed). The biogas results show a general increase compared to the conventional digestion, being the highest production per unit of digester for the process combining the thermal pre-treatment and AD (1.4 L biogas/L digester day compared to the value of 0.26 obtained in conventional digesters). The dewaterability of the digestate became enhanced for processes TH + AD and TPAD when compared with the conventional digestate, while it became worse for processes US + AD and TAD. In all the research lines, the viscosity in the digester was smaller compared to the conventional (which is a key factor for process performance and economics), and both thermal pre-treatment and thermophilic digestion (TAD and TPAD) assure a pathogen free digestate. PMID- 22097011 TI - The impact of cyanobacteria on growth and death of opportunistic pathogenic bacteria. AB - Climate change may cause increased microbial growth in water sources and more knowledge is required on how this may affect the hygienic water quality, i.e., whether increased occurrence of cyanobacteria and algae may stimulate the growth rate of opportunistic pathogenic bacteria. Laboratory experiments were performed to investigate if the presence of the cyanobacteria Anabanea lemmermannii and Microcystis aeruginosa affected the survival and growth rate of the opportunistic pathogenic bacteria Aeromonas hydrophila and Pseudomonas aeruginosa, and the faecal indicators Escherichia coli and coliforms. Cyanobacteria were cultured in bottles containing the nutrient-poor medium 02. Sewage, A. hydrophila or P. aeruginosa was added to cyanobacterial cultures and the bacterial growth and survival was followed. E. coli and coliforms from sewage died within few days and the decay rate was not affected by the presence of cyanobacteria. The presence of Anabaena stimulated the growth rate of P. aeruginosa, but had no effect on the growth rate of A. hydrophila. Microcystis had no effect on the growth rate of P. aeruginosa and an inhibiting effect on the growth rate of A. hydrophila. PMID- 22097012 TI - Application of sequencing batch membrane bioreactors (SB-MBR) for the treatment of municipal wastewater. AB - Sequencing batch membrane bioreactors can be a good option in up-grading small municipal plant and for industrial applications, maintaining some of the advantages of both original technologies (effluent quality improvement, flexibility and simplicity of realization, operation and control). In this study, the effects of volumetric exchange ratio (VER) and aeration/filtration strategy have been evaluated. Moreover, with the adoption of cycles shorter than 8 h, the opportunity of further simplification of the membrane operation has been tested by choosing a continuous filtration mode instead of the usual short cycle of permeation/relaxation. Two lab-scales MBR equipped with Zenon hollow fiber modules were fed on real primary effluent. For all tests, hydraulic retention time of 10 h and sludge retention time of 60 days have been adopted. Different cycles have been investigated, lasting between 1 and 8 h and all comprising an anoxic phase to allow for denitrification. Operation at low VER resulted in better effluent quality with no limitations to the denitrification phase. For VER >33% a pre-aeration step was required before effluent withdrawal for optimal ammonium removal. Moreover, VER appeared to have limited negative effect on sludge concentration and yield, while the membrane cleaning frequency slightly increased for increasing VER. PMID- 22097013 TI - Three stages MBR (methanogenic, aerobic biofilm and membrane filtration) for the treatment of low-strength wastewaters. AB - The use of a new three stages MBR process with a first methanogenic UASB stage, a second stage with aerobic biofilm growing on small carrier elements maintained in suspension and third stage with membrane filtration module is presented. The objective of the first methanogenic chamber is to diminish COD of the raw wastewater, producing a biogas rich in methane, and decrease the sludge production. In the second stage, the remaining soluble biodegradable COD is oxidized by heterotrophs. In the third stage, the membrane modules could be operated at higher fluxes than those reported for AnMBR systems, and similar to those obtained in aerobic MBRs. In this sense, the concept of these three stages MBR is to join the advantages of the methanogenic and aerobic membrane bioreactor processes, by reducing energy requirements for aeration, producing biogas with high methane percentage and a permeate with very low COD content. A synthetic wastewater was fed to the three stages MBR. COD in the influent was between 200 and 1,200 mg/L, ammonium ranged from 10 to 35 mg/L and phosphorous concentration was 8 mg/L. OLR in-between 1 and 3 kg COD/(m3 d) and a HRT of 13-21 h were applied. Temperature was between 17.5 and 23.2 degrees C. During the whole operating period the COD removal efficiencies were in the range of 90 and 96% of which in between 40 and 80% was removed in the first methanogenic chamber. Biogas production with methane content between 75 and 80% was observed. With regard to membrane operation, average permeabilities around 150 L/(m2 h bar) were achieved, operating with fluxes of 11-15 L/(m2 h). PMID- 22097014 TI - Clonal variation in reproductive response to temperature by a potential bulking control agent, Lecane inermis (Rotifera). AB - The novel idea of using rotifers Lecane inermis (Rotifera, Monogononta) as a tool to overcome activated sludge bulking generates an on-going need to study rotifer biology. The results of biological research on rotifers can serve to improve the method so that it can be most effective when applied in treatment plants. The aim of this study was to test the effect of temperature on four selected rotifer clones originating from different treatment plants. The rate of population development from a single individual (parthenogenetic female) during a 10-day experiment was measured at three temperatures: 8, 15 and 20 degrees C. The temperatures used reflect the annual temperature distribution in the majority of municipal wastewater treatment plants in the temperate zone. The growth rate coefficient (r) and doubling time (tD) were calculated for each clone. Under the most favourable conditions (20 degrees C), rvalues varied between 0.41 and 0.47 d and doubling time between 1.5 and 1.7 d. At a temperature of 15 degrees C, the doubling time was approximately two times longer (2.5-3.4 d). The strongest intraspecific variations were observed at the lowest temperature of 8 degrees C. At this temperature, one of the clones almost failed to proliferate, and another exhibited a doubling time of 7.9 d. The doubling times were a few times greater for the remaining two clones (60 d for Lk1, 33.3 d for Lk4). These results could be very useful in predicting the chances that the rotifers would survive in a biological reactor in a wastewater treatment plant at the temperatures used in these reactors. PMID- 22097015 TI - Kinetics of heterotrophic biomass and storage mechanism in wetland cores measured by respirometry. AB - Although oxygen uptake rate has been widely used in activated sludge for measuring kinetic and stoichiometric parameters or for wastewater characterization, its application in constructed wetlands (CWs) cores has been recently proposed. The aim of this research is to estimate the kinetic and stoichiometric parameters of the heterotrophic biomass in CW cores. Respirometric tests were carried out with pure carbonaceous substrate and real wastewater. Endogenous respiration was about 2 gO2 m(-3) h(-1) (per unit of bed volume), while the kinetic parameters obtained for COD oxidation were very high (maximum rate per unit of bed volume of 10.7-26.8 gCOD m(-3) h(-1)) which indicates high biodegradation potential in fully aerobic environment. Regarding to stoichiometric parameter, the maximum growth yield, Y(H), was 0.56-0.59 mgCOD/mgCOD, while the storage yield, Y(STO), was 0.75-0.77 mgCOD/mgCOD. The storage mechanism was observed in CW cores during COD oxidation, which leads to the transformation of the external soluble substrate in internal storage products, probably as response to intermittent loads applied in CW systems, transient concentrations of readily biodegradable substrate and alternance of feast/famine periods. PMID- 22097016 TI - A novel technology for on-site cupric oxide recovery from cupric chloride etchant waste. AB - For on-site copper recovery in print circuit board factories, we propose a novel technology to obtain cupric oxide with a low content ratio of chloride from high chloride concentration waste, such as cupric chloride etchant waste. Our technology is designed to avoid formation of double salt and accumulation of cupric hydroxide. In the proposed method, etchant waste mixed with hydrogen peroxide solution is added to sodium hydroxide solution by stepwise addition. We performed lab-scale experiments on the influence of reaction pH conditions on the content ratio of chloride in recovering cupric oxide. The results show that recycled cupric oxide tends to contain a lower content ratio of chloride under higher starting temperatures and higher final pH conditions of the reaction. We also confirmed the optimized conditions; the starting temperature of the sodium hydroxide solution is higher than 70 degrees C, and the final pH of the reaction is 11.5 to 12. Based on the optimized temperature and pH conditions, we also performed a pilot trial to recover cupric oxide from real etchant waste. Then, we successfully obtained cupric oxide with a content ratio of chloride in 80 mg Cl/kg-CuO. PMID- 22097017 TI - Synthesis of polyaspartic acid-aminobenzenesulfonic acid grafted copolymer and its scale inhibition performance and dispersion capacity. AB - Polysuccinimide (abridged as PSI) was synthesized by urea and maleic anhydride. Aminobenzenesulfonic acid (ABSA) was introduced at different mole ratio to PSI to generate polyaspartic acid (abridged as PASP)/ABSA graft copolymer. The scale inhibition behavior of resultant PASP/ABSA copolymer was evaluated by using static scale inhibition method. The transmittance of the supernatant of the copolymer solution was measured to evaluate its dispersion ability for ferric oxide. The corrosion inhibition performance of the copolymer for iron plates immersed in the refined testing water (including 0.555 g of CaCl2 2H2O, 0.493 g of MgSO4 7H2O, 50 mg PASP/ABSA graft copolymer and 0.168 g of NaCl) was tested. It was found that PASP/ABSA copolymer was able to efficiently inhibit CaCO3 and Ca3(PO4)2 scales and had good corrosion inhibition ability as well, and it also had good dispersion ability for Fe2O3. Besides, the inhibition efficiency of PASP/ABSA against CaCO3 and Ca3(PO4)2 scales and its dispersion capacity for Fe2O3 was highly dependent on dosage. The reason may lie in that PASP/ABSA copolymer simultaneously possesses carboxylic ion and sulfonic group which can chelate Ca2+ to form stabilized and dissoluble chelates, resulting in increase of solubility of calcium salts in water. Also it may lie in that the introduction of acidic hydrophilic sulfonic group with a strong electrolytic capacity into PASP molecule simultaneously enhances the dispersion of the inhibitor molecules and hinders the formation of Ca3(PO4)2 scale. PMID- 22097018 TI - The role of SSVF and SSHF beds in concentrated wastewater treatment, design recommendation. AB - The return flows of reject water from sewage sludge dewatering alter the activated sludge process in a conventional WWTP and increase TN concentration in the final effluent from WWTP. The objective of the investigation carried out was to consider the application of multistage treatment wetland (MTW) for the treatment of reject water from sewage sludge dewatering in a centrifuge (RWC). This paper aims to present the design and performance of each stage of the treatment as well as the efficiency of total MTW. The full scale pilot plant for RWC, consisting of two vertical flow beds (SS VF) working in series, followed by an horizontal flow bed (SS HF), was built in 2008. The applied configuration ensured a very high removal efficiency of principal pollutant (COD - 76.0% and NH4+-N - 93.6%). In the investigated facilities, the SS VF beds ensured an effective removal of nitrogen compounds, especially NH4+-N, whereas the decomposition of hardly degradable Org-N and COD took place in SS HF. This research illustrates that the MTW could be successfully applied for the treatment of RWC. PMID- 22097019 TI - Life cycle assessment of an intensive sewage treatment plant in Barcelona (Spain) with focus on energy aspects. AB - Life Cycle Assessment was used to evaluate environmental impacts associated to a full-scale wastewater treatment plant (WWTP) in Barcelona Metropolitan Area, with a treatment capacity of 2 million population equivalent, focussing on energy aspects and resources consumption. The wastewater line includes conventional pre treatment, primary settler, activated sludge with nitrogen removal, and tertiary treatment; and the sludge line consists of thickening, anaerobic digestion, cogeneration, dewatering and thermal drying. Real site data were preferably included in the inventory. Environmental impacts of the resulting impact categories were determined by the CLM 2 baseline method. According to the results, the combustion of natural gas in the cogeneration engine is responsible for the main impact on Climate Change and Depletion of Abiotic Resources, while the combustion of biogas in the cogeneration unit accounts for a minor part. The results suggest that the environmental performance of the WWTP would be enhanced by increasing biogas production through improved anaerobic digestion of sewage sludge. PMID- 22097020 TI - PLIO: a generic tool for real-time operational predictive optimal control of water networks. AB - This paper presents a generic tool, named PLIO, that allows to implement the real time operational control of water networks. Control strategies are generated using predictive optimal control techniques. This tool allows the flow management in a large water supply and distribution system including reservoirs, open-flow channels for water transport, water treatment plants, pressurized water pipe networks, tanks, flow/pressure control elements and a telemetry/telecontrol system. Predictive optimal control is used to generate flow control strategies from the sources to the consumer areas to meet future demands with appropriate pressure levels, optimizing operational goals such as network safety volumes and flow control stability. PLIO allows to build the network model graphically and then to automatically generate the model equations used by the predictive optimal controller. Additionally, PLIO can work off-line (in simulation) and on-line (in real-time mode). The case study of Santiago-Chile is presented to exemplify the control results obtained using PLIO off-line (in simulation). PMID- 22097021 TI - Treatment of wastewater from a cotton dyeing process with UV/H2O2 using a photoreactor covered with reflective material. AB - Wastewater containing several dyes, including sulfur black from the dyeing process in a textile mill, was treated using a UV/H2O2 process. The wastewater was characterized by a low BOD/COD ratio, intense color and high acute toxicity to the algae species Pseudokirchneriella subcaptata. The influence of the pH and H2O2 concentration on the treatment process was evaluated by a full factorial design 22 with three replicates of the central experiment. The removal of aromatic compounds and color was improved by an increase in the H2O2 concentration and a decrease in pH. The best results were obtained at pH 5.0 and 6 g L(-1). With these conditions and 120 min of UV irradiation, the removal of the color, aromatic compounds and COD were 74.1, 55.1 and 44.8%, respectively. Under the same conditions, but using a photoreactor covered with aluminum foil, the removal of the color, aromatic compounds and COD were 92.0, 77.6 and 59.4%, respectively. Moreover, the use of aluminum foil reduced the cost of the treatment by 40.8%. These results suggest the potential application of reflective materials as a photoreactor accessory to reduce electric energy consumption during the UV/H2O2 process. PMID- 22097022 TI - A feasibility study of magnetic separation of magnetic nanoparticle for forward osmosis. AB - It was recently reported that a UK company has developed a naturally non-toxic magnetoferritin to act as a draw solute for drawing water in forward osmosis process. The gist of this technology is the utilization of the magnetic nanoparticle and high-gradient magnetic separation for draw solute separation and reuse. However, any demonstration on this technology has not been reported yet. In this study, a feasibility test of magnetic separation using magnetic nanoparticle was therefore performed to investigate the possibility of magnetic separation in water treatment such as desalination. Basically, a magnetic separation system consisted of a column packed with a bed of magnetically susceptible wools placed between the poles of electromagnet and Fe3O4 magnetic nanoparticle was used as a model nanoparticle. The effect of nanoparticle size to applied magnetic field in separation column was experimentally investigated and the magnetic field distribution in a magnet gap and the magnetic field gradient around stainless steel wool wire were analyzed through numerical simulation. The amount of magnetic nanoparticle captured in the separator column increased as the magnetic field strength and particle size increased. As a result, if magnetic separation is intended to be used for draw solute separation and reuse, both novel nanoparticle and large-scale high performance magnetic separator must be developed. PMID- 22097023 TI - High performance liquid chromatography-tandem mass spectrometry for rapid and sensitive analysis of six polycyclic aromatic hydrocarbons in wastewater. AB - A sensitive and fast method was developed to quantitatively analyse the six polycyclic aromatic hydrocarbons (fluoranthene (FLT), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a] pyrene (Bap), benzo[ghi]perylene (BghiP) and indeno[1,2,3-cd]pyrene (INPY)) by high performance liquid chromatography (UPLC) coupling with tandem mass spectrometry (MS/MS). Chromatographic separation was performed on a Waters Acquity UPLC BEHC18 column (1.7 microm, 2.1 mm x 50 mm). A 0.2 microm precolumn filter was used to protect the analytical column. Mobile phase Awas acetonitrile containing 0.5% toluene. Mobile phase B was water. Linearity of detection was in the range of 1-100 microg L(-1); LOD of 5 PAHs were lower than 0.1 microg L(-1); LOQ were 0.2 microg L(-1) except for benzo[k]fluoranthene. The LOD and the LOQ of benzo[k]fluoranthene were respectively 0.1 microg L(-1) and 0.8 microg L(-1). Wastewater samples collected from two wastewater treatment plants were determined using this method respectively. Recovery of all compounds varied from 67.8 +/- 10.6% to 113.2 +/- 7.2%. In comparison with the existing methods, this rapid method saves time and solvent and improves instrument sample throughput by 2-5 fold. PMID- 22097024 TI - Micropollutants in stormwater runoff and combined sewer overflow in the Copenhagen area, Denmark. AB - Stormwater runoff contains a broad range of micropollutants. In Europe a number of these substances are regulated through the Water Framework Directive, which establishes Environmental Quality Standards (EQSs) for surface waters. Knowledge about discharge of these substances through stormwater runoff and combined sewer overflows (CSOs) is essential to ensure compliance with the EQSs. Results from a screening campaign including more than 50 substances at four stormwater discharge locations and one CSO in Copenhagen are reported here. Heavy metal concentrations were detected at levels similar to earlier findings, e.g., with copper found at concentrations up to 13 times greater than the Danish standard for surface waters. The concentration of polyaromatic hydrocarbons (PAHs) exceeded the EQSs by factors up to 500 times for stormwater and 2,000 times for the CSO. Glyphosate was found in all samples whilst diuron, isoproturon, terbutylazine and MCPA were found only in some of the samples. Diethylhexylphthalate (DEHP) was also found at all five locations in concentrations exceeding the EQS. The results give a valuable background for designing further monitoring programmes focusing on the chemical status of surface waters in urban areas. PMID- 22097025 TI - Restoration of stormwater retention capacity at the allotment-scale through a novel economic instrument. AB - Urbanisation results in changes to runoff behaviour which, if not addressed, inevitably degrade receiving waters. To date, most stormwater management has focussed on the streetscape and public open space. Given that much of the catchment imperviousness is located on private land, we developed and tested a novel economic instrument (a uniform price auction) for encouraging allotment scale stormwater retention. We evaluated bids using an integrated environmental benefit index (EBI), based on the ability of the proposed works to reduce runoff frequency, pollutant loads and to reduce potable water demand. The uniform price auction resulted in 1.4 ha of impervious areas being effectively 'disconnected' from the stormwater system. The EBI provided an objective and transparent method of comparing bids, which varied in the type of works proposed (e.g. rainwater tank, rain-garden), the cost and the resulting environmental benefit. Whilst the pilot auction was a success, the public subsidy of works undertaken was around 85%, meaning that property owners a relatively small private benefit in the works. Future auction rounds will be revised to (i) test an EBI which is more focussed on the protection of streams (assessing changes to runoff frequency, baseflow volumes and water quality) and (ii) provide an auction process which is simpler to understand, and provides greater practical support for landholders who wish to undertake works. PMID- 22097026 TI - Heavy metals, PAHs and toxicity in stormwater wet detention ponds. AB - Concentrations of 6 different heavy metals and total polycyclic aromatic hydrocarbons (PAHs) were determined in stormwater runoff and in the pond water of two Danish wet detention ponds. The pond water samples were analyzed for toxic effects, using the algae Selenastrum capricornutum as a test organism. Stormwater and pond water from a catchment with light industry showed high levels of heavy metals, especially zinc and copper. The pond water showed high toxic effects and copper were found to be the main toxicant. Additionally, a large part of the copper was suspected to be complex bound, reducing the potential toxicity of the metal. Another catchment (residential) produced stormwater and pond water with moderate concentration of heavy metals. The pond water occasionally showed toxic effects but no correlation between heavy metals and toxicity was identified. PAHs concentrations were for both catchments low and no correlations between PAH concentrations in the pond and toxicity were found. PMID- 22097027 TI - Proposal for identification methodology for urban agglomerations according to directive 91/271/EEC on wastewater treatment. AB - This paper discusses the problem of the identification and definition of the urban agglomerations in accordance with Directive 91/271/EC. The aim of this identification is to guarantee a satisfactory level of treatment for urban wastewaters and the achievement of the quality objectives for water bodies. The methodology employed, taking into account the existing planning tools in the water service sector, has been based on official national census data, on the Water Protection Plan, on the predictions of Water Service Plans prepared by each Water Authority and on detailed indications provided by the Authorities themselves. The proposed approach, obtained with geographic information systems applications and the calculation of pollution loads, is described and tested in the Veneto region, Italy. In the final part of the paper some considerations on the results obtained are presented and discussed. PMID- 22097028 TI - The use of CFD modelling to optimise measurement of overflow rates in a downstream-controlled dual-overflow structure. AB - The measurement of the flow through complex combined sewer overflow structures in the frame of automated monitoring remains difficult. In this paper, a methodology based on the use of computational fluid dynamics (CFD) modelling in order to improve the instrumentation of a downstream-controlled dual-overflow structure is presented. The dual-overflow structure is composed of two combined sewer overflows (CSOs) connected by a rectangular channel and controlled by a downstream gate located at the entry of the Meyzieu waste water treatment plant (close to Lyon, France). The analysis of the CFD results provides: (i) a better understanding of the interaction between the two CSOs--that means the hydraulic operation, the hydrodynamic behaviour, the backflow effect--and (ii) an ability to optimise the location of the water depth sensor. The measured water depth is used to assess the overflow rate by means of a numerical relationship. Uncertainties are also assessed. PMID- 22097029 TI - The study of adsorption characteristics of electrospun polymer nanofibers for benzenes in water. AB - The adsorption properties of benzene, p-dichlorobenzene and nitrobenzene on polymer nanofibers were studied. Compared with polyacrylonitrile nanofiber, polystyrene (PS) nanofiber presented better adsorption performance. Langmuir and Freundlich adsorption models were used for the mathematical description of adsorption equilibria, and Freundlich isotherms fitted better. Kinetic studies showed that the adsorption of PS nanofiber followed pseudo first-order model. Various thermodynamic parameters such as standard free energy (delta G), enthalpy (delta H) and entropy (delta S) were calculated for predicting the adsorption nature of PS nanofiber for three benzenes, which indicated that the adsorption was spontaneous and a physical process. The regeneration efficiency maintains over 80% after five cycles of adsorption/desorption tests. It showed that PS nanofibers are promising candidates for adsorption and removal of aromatic hydrocarbons from water. PMID- 22097030 TI - Methane conversion efficiency as a simple control parameter for an anaerobic digester at high loading rates. AB - The anaerobic digestion process is globally applied to the treatment of highly concentrated wastes such as industrial and rural effluents, and sewage sludge. However, it is known to be relatively unstable. When loaded with high concentrations of organic material, unwanted volatile fatty acids (VFA) are often produced rather than methane (CH4) gas which can lead to digester acidification and failure. This study investigated digester behaviour under high loading rates, testing the usefulness of stoichiometric methane conversion efficiency as a digester control parameter at high loading rates. Our results show that, in general, the CH4 production rate was proportional to the feed rate (loading rate). However, at very high loading rates, the CH4 production rate was not proportional to the increase in the feeding rate. Consequently, VFA accumulated and the H2 partial pressure increased. The proportionality of the loading rate and gas production rate is stoichiometrically expressed as the conversion efficiency. We found that conversion efficiency was a useful indicator as an early warning of digester imbalance. The digester remained stable at conversion efficiencies above 75%. Dropping below 70% signified the onset of digester failure. As loading rate and methane production data are readily available on line in most anaerobic digestion plants, the conversion efficiency can be monitored on-line and used as an efficient control technique to maintain safe operation of anaerobic digesters at high loading rates. PMID- 22097031 TI - Priority organic pollutants in the urban water cycle (Toulouse, France). AB - Application of the European Water Framework Directive requires Member States to have better understanding of the quality of surface waters in order to improve knowledge of priority pollutants. Xenobiotics in urban receiving waters are an emerging concern. This study proposes a screening campaign of nine molecular species of xenobiotics in a separated sewer system. Five sites were investigated over one year in Toulouse (France) using quantitative monitoring. For each sample, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, nonylphenols, diethelhexylphthalate, linear alkylbenzene sulphonates, methyl tert butylether, total hydrocarbons, estradiol and ethinylestradiol were analysed. Ground, rain and roof collected water concentrations are similar to treated wastewater levels. Run-off water was the most polluted of the five types investigated, discharged into the aquatic environment. The wastewater treatment plant reduced xenobiotic concentrations by 66% before discharge into the environment. Regarding environmental quality standards, observed concentrations in waters were in compliance with standards. The results show that xenobiotic concentrations are variable over time and space in all urban water compartments. PMID- 22097032 TI - Automatic characterisation of primary, secondary and mixed sludge inflow in terms of the mathematical generalised sludge digester model. AB - This paper presents the characterisation procedure of different types of sludge generated in a wastewater treatment plant to be reproduced in a mathematical model of the sludge digestion process. The automatic calibration method used is based on an optimisation problem and uses a set of mathematical equations related to the a priori knowledge of the sludge composition, the experimental measurements applied to the real sludge, and the definition of the model components. In this work, the potential of the characterisation methodology is shown by means of a real example, taking into account that sludge is a very complex matter to characterise and that the models for digestion also have a considerable number of model components. The results obtained suit both the previously reported characteristics of the primary, secondary and mixed sludge, and the experimental measurements specially done for this work. These three types of sludge have been successfully characterised to be used in complex mathematical models. PMID- 22097033 TI - Models for nitrification process design: one or two AOB populations? AB - Models for engineering design of nitrifying systems use one ammonia oxidizer biomass (AOB) state variable. A simple extension using two AOB populations allows a more accurate prediction of nitrification systems at switching process environments. These two AOB subpopulations are characterized by two different sets of kinetic parameters. Selection pressure and competition between the two functional AOB populations are determined by process conditions as demonstrated by three case studies: Case study I describes dynamics of two AOB populations showing different temperature sensitivities (modified Arrhenius term on growth and decay) when bioaugmented from the warm sidestream treatment environment to the cold mainstream and vice-versa. Case study II investigates competition between fast growing micro-strategists and k-strategists adjusted to low ammonia levels depending on the internal mixed liquor recycle rate (IMLR). Case study III shows that AOB transferred from the waste activated sludge of an SBR to the parallel continuous flow system with different decay kinetics can overgrow or coexist with the original population. PMID- 22097034 TI - Three years of operation of the urine diversion system at GTZ headquarters in Germany: user opinions and maintenance challenges. AB - In the main office building of GTZ in Eschborn, Germany a resource-oriented sanitation system containing urine diversion (UD) toilets and waterless urinals has been in operation since 2006. After 2.5 years of operating the system, a first overall evaluation of the system in terms of its acceptance amongst the users and the cleaning staff was conducted by carrying out two surveys and many interviews. The overall result is that most of the users appreciate the sanitation concept in theory but have problems with the technical design of the particular type of UD flush toilets installed here. The survey results also gave some directions towards which hygiene devices the users would appreciate in order to overcome their reluctance to sit down on the toilet seat in public buildings (the sitting being necessary for correct operation of the urine valve to separate urine from flush water). Also, it is difficult to convince the cleaning and facility maintenance staff of the necessity of special cleaning and preventative maintenance routines. Hence, before such systems can be widely used, clear cleaning routines and maintenance instruction are required as well as certain technical modifications of this type of UD flush toilets to optimise the urine/water separation and the flushing properties of the toilet. PMID- 22097035 TI - Nitrogen removal and ammonia-oxidising bacteria in a vertical flow constructed wetland treating inorganic wastewater. AB - Nitrogen removal performance and the ammonia-oxidising bacterial (AOB) community were assessed in the batch loaded 1.3 ha saturated surface vertical flow wetland at CSBP Ltd, a fertiliser and chemical manufacturer located in Kwinana, Western Australia. From September 2008 to October 2009 water quality was monitored and sediment samples collected for bacterial analyses. During the period of study the wetland received an average inflow of 1,109 m3/day with NH3-N = 40 mg/L and NO3-N = 23 mg/L. Effluent NH3-N and NO3-N were on average 31 and 25 mg/L, respectively. The overall NH3-N removal rate for the period was 1.2 g/m2/day indicating the nitrifying capacity of the wetland. The structure of the AOB community was analysed using group specific primers for the ammonia monooxygenase gene (amoA) by terminal restriction fragment length polymorphism and by clone libraries to identify key members. The majority of sequences obtained were most similar to Nitrosomonas sp. while Nitrosospira sp. was less frequent. Another two vertical flow wetlands, 0.8 ha each, were commissioned at CSBP in July 2009, since then the wetland in this study has received nitrified effluent from these two new cells. PMID- 22097036 TI - Occurrence of hydrodynamic cavitation. AB - In this paper, the conditions under which cavitation (or liquid film rupture) can or cannot occur in thin layers of moving liquid are derived for three typical cases. At the same time, expressions depending on geometrical and movement parameters, where cavitation might start, are given. The results are obtained using simple engineering terms, which can be used in cases whether it is necessary to avoid cavitation or to induce it. PMID- 22097037 TI - Spectrophotometric characterization of human impacted surface waters in the Moselle watershed. AB - In order to characterize the pollution discharged into the Moselle River and some of its tributaries, spectroscopic techniques, namely UV-vis spectroscopy and synchronous fluorescence spectroscopy, have been combined. UV-visible spectra were analysed using the maximum of the second derivative at 225 nm (related to nitrates), the SUVA254 and E2/E3 indices (related to the nature of organic matter). Synchronous fluorescence spectra (delta lambda = 50 nm) presented different shapes depending upon the type of pollution. The pollution results from anthropogenic activities: untreated domestic sewage due to misconnections in a periurban river, effluent from urban WWTPS, agricultural runoff (nitrates) in several streams, discharge from a paper mill (humic-like substances due to wood processing) and from steel mills (PAHs). PMID- 22097038 TI - Grey water treatment in upflow anaerobic sludge blanket (UASB) reactor at different temperatures. AB - The treatment of grey water in two upflow anaerobic sludge blanket (UASB) reactors, operated at different hydraulic retention times (HRTs) and temperatures, was investigated. The first reactor (UASB-A) was operated at ambient temperature (14-25 degrees C) and HRT of 20, 12 and 8 h, while the second reactor (UASB-30) was operated at controlled temperature of 30 degrees C and HRT of 16, 10 and 6 h. The two reactors were fed with grey water from 'Flintenbreite' settlement in Luebeck, Germany. When the grey water was treated in the UASB reactor at 30 degrees C, total chemical oxygen demand (CODt) removal of 52-64% was achieved at HRT between 6 and 16 h, while at lower temperature lower removal (31-41%) was obtained at HRT between 8 and 20 h. Total nitrogen and phosphorous removal in the UASB reactors were limited (22-36 and 10-24%, respectively) at all operational conditions. The results showed that at increasing temperature or decreasing HRT of the reactors, maximum specific methanogenic activity of the sludge in the reactors improved. As the UASB reactor showed a significantly higher COD removal (31-64%) than the septic tank (11-14%) even at low temperature, it is recommended to use UASB reactor instead of septic tank (the most common system) for grey water pre-treatment. Based on the achieved results and due to high peak flow factor, a HRT between 8 and 12 h can be considered the suitable HRT for the UASB reactor treating grey water at temperature 20-30 degrees C, while a HRT of 12-24 h can be applied at temperature lower than 20 degrees C. PMID- 22097039 TI - Urine nitrification and sewer discharge to realize in-sewer denitrification to simplify sewage treatment in Hong Kong. AB - The chemically enhanced primary treatment works in Hong Kong will be upgraded for biological nitrogen removal. This study proposed a novel approach to waive the upgrading by urine source-separation, onsite nitrification and discharge of nitrified urine into sewers to achieve in-sewer denitrification. Human urine was collected and a lab-scale experiment for full urine nitrification was conducted. The results showed that full nitrification was achieved with alkaline addition. Simulation of nitrified urine discharge into an 8-km pressure main in Hong Kong was conducted with a quasi-2D dynamic sewer model developed from a previously calibrated sewer biofilm model. It was assumed that 70% of the residents' urine was collected and fully nitrified on-site. The simulation results revealed that the proposed approach is effective in removal of nitrogen within the sewer, which decreases ammonia-N at the sewer outlet to a level required for secondary effluent discharge in Hong Kong. PMID- 22097040 TI - Comparing the microbial characteristics of rainwater in two operating rainwater tanks with different surface-to-volume ratios. AB - In this study, the microbial characteristics of rainwater in two tanks with different surface-to-volume ratios were investigated and compared to determine how the internal design features of storage tanks affect water quality. The particle and nutrient parameters of the rainwater, including turbidity, suspended solids, total organic carbon, and total phosphate, were lower in Tank 2, which had a surface-to-volume ratio 7.5 times greater than that of Tank 1. In addition, although the rainwater was collected from the same catchment area, the water in Tank 1 had greater numbers of bacteria, and the bacterial communities in the water differed between the two storage tanks. It appears that the differences in the inside surface structures of the rainwater tanks affected the microbial ecosystems. Increasing the surface-to-volume ratio in rainwater tanks may affect rainwater quality, because this extends the area for biofilm development. Further study of the role of biofilm in rainwater tank is required precisely, and its function needs to be considered in the design and management of rainwater tanks. PMID- 22097041 TI - The significance of interactions between organic compounds on low pressure membrane fouling. AB - Fouling of hollow fibre microfiltration and ultrafiltration membranes by solutions of pure organic compounds and mixtures of these compounds was studied with a backwashable membrane filtration apparatus. Small molecular weight compounds resulted in little fouling, while their polymeric analogues resulted in more severe fouling. Neutrally charged dextran resulted in minor, irreversible fouling, that was considered to be associated with blocking of small pores. Cationically charged chitosan produced gross fouling for which the extent of reversibility increased with salt addition. Anionically charged alginic acid resulted in gross irreversible fouling, except when being filtered by a hydrophilic membrane in the absence of calcium where a high degree of flux recovery was observed. Calcium addition to the alginic acid solutions resulted in gross fouling of all membranes and calcium bridging was considered to be responsible for this behaviour. Greater fouling occurred on the hydrophilic membrane compared to the hydrophobic membranes for bovine serum albumin (BSA) solutions, and this was considered to be due to physical blocking of pores, because addition of calcium resulted in lower flux declines. Addition of BSA and calcium to alginic acid solutions resulted in lower flux recoveries for the alginic acid system, consistent with the proposition that interactions between polysaccharide and other compounds are required for irreversible fouling on hydrophilic membranes. PMID- 22097042 TI - Soil aquifer treatment using advanced primary effluent. AB - Soil aquifer treatment (SAT) using primary effluent (PE) is an attractive option for wastewater treatment and reuse in many developing countries with no or minimal wastewater treatment. One of the main limitations of SAT of PE is rapid clogging of the infiltration basin due to high suspended solid concentrations. Some pre-treatment of PE before infiltration is likely to reduce this limitation, improve performance of SAT and help to implement this technology effectively. The effects of three pre-treatment options namely sedimentation (SED), coagulation (COAG) and horizontal roughing filtration (HRF) on SAT were analyzed by conducting laboratory-scale batch and soil column experiments. The sedimentation and coagulation pre-treatments led to less head loss development and reduction of clogging effect. The head loss development in soil column using PE + COAG and PE + SED was reduced by 85 and 72%, respectively, compared to PE alone without any pretreatment. The overall dissolved organic carbon (DOC) removal of pre treatments and soil column collectively were 34, 44, 51 and 43.5% for PE without any pre-treatment, PE + SED, PE + COAG and PE + HRF, respectively. Coagulation pre-treatment of PE was found to be the most effective option in terms of suspended solids, DOC and nitrogen removal. Sedimentation pre-treatment of PE could be attractive where land is relatively less expensive for the construction of sedimentation basins. PMID- 22097043 TI - Autogenerative high pressure digestion: anaerobic digestion and biogas upgrading in a single step reactor system. AB - Conventional anaerobic digestion is a widely applied technology to produce biogas from organic wastes and residues. The biogas calorific value depends on the CH, content which generally ranges between 55 and 65%. Biogas upgrading to so-called 'green gas', with natural gas quality, generally proceeds with add-on technologies, applicable only for biogas flows > 100 m3/h. In the concept of autogenerative high pressure digestion (AHPD), methanogenic biomass builds up pressure inside the reactor. Since CO2 has a higher solubility than CH4, it will proportion more to the liquid phase at higher pressures. Therefore, AHPD biogas is characterised by a high CH4 content, reaching equilibrium values between 90 and 95% at a pressure of 3-90 bar. In addition, also H2S and NH3 are theoretically more soluble in the bulk liquid than CO2. Moreover, the water content of the already compressed biogas is calculated to have a dew point <--10 degrees C. Ideally, high-quality biogas can be directly used for electricity and heat generation, or injected in a local natural gas distribution net. In the present study, using sodium acetate as substrate and anaerobic granular sludge as inoculum, batch-fed reactors showed a pressure increase up to 90 bars, the maximum allowable value for our used reactors. However, the specific methanogenic activity (SMA) of the sludge decreased on average by 30% compared to digestion at ambient pressure (1 bar). Other results show no effect of pressure exposure on the SMA assessed under atmospheric conditions. These first results show that the proposed AHPD process is a highly promising technology for anaerobic digestion and biogas upgrading in a single step reactor system. PMID- 22097044 TI - Adsorption characteristics of methylene blue onto agricultural wastes lotus leaf in bath and column modes. AB - The adsorption potential of lotus leaf to remove methylene blue (MB) from aqueous solution was investigated in batch and fixed-bed column experiments. Langmuir, Freundlich, Temkin and Koble-Corrigan isotherm models were employed to discuss the adsorption behavior. The results of analysis indicated that the equilibrium data were perfectly represented by Temkin isotherm and the Langmuir saturation adsorption capacity of lotus leaf was found to be 239.6 mg g(-1) at 303 K. In fixed-bed column experiments, the effects of flow rate, influent concentration and bed height on the breakthrough characteristics of adsorption were discussed. The Thomas and the bed-depth/service time (BDST) models were applied to the column experimental data to determine the characteristic parameters of the column adsorption. The two models were found to be suitable to describe the dynamic behavior of MB adsorbed onto the lotus leaf powder column. PMID- 22097045 TI - Adsorption behavior of activated carbon derived from pyrolusite-modified sewage sludge: equilibrium modeling, kinetic and thermodynamic studies. AB - Activated carbon was developed from sewage sludge using pyrolusite as an additive. It was demonstrated that the removal efficiency of two synthetic dyes (Tracid orange GS and Direct fast turquoise blue GL) by the produced adsorbent was up to 97.6%. The activated carbon with pyrolusite addition had 38.2% higher surface area, 43.8% larger micropore and 54.4% larger mesopore production than ordinary sludge-based activated carbons. Equilibrium adsorption isotherms and kinetics were also investigated based on dyes adsorption tests. The experimental data were analyzed by the Langmuir and Freundlich models of adsorption, and the results fitted well to the Langmuir isotherm. The kinetic data have been analyzed using pseudo-first-order, pseudo-second-order and intraparticle diffusion equation. The experimental data fitted very well with pseudo-second-order kinetic model. Activation energies for the adsorption processes ranged between 8.7 and 19.1 kJ mol 1. Thermodynamic parameters such as standard free energy (deltaG0), standard enthalpy (deltaH0) and standard entropy (deltaS0) were evaluated. The adsorption of these two dyes on the activated carbon was found to be a spontaneous and endothermic process in nature. PMID- 22097047 TI - The development of a code of practice for single house on-site wastewater treatment in Ireland. AB - The performance of six separate percolation areas was intensively monitored to ascertain the attenuation effects of unsaturated subsoils with respect to on-site wastewater effluent: three sites receiving septic tank effluent, the other three sites receiving secondary treated effluent. The development of a biomat across the percolation areas receiving secondary treated effluent was restricted on these sites compared to those sites receiving septic tank effluent. This created significant differences in terms of the hydraulic loading on the percolation areas with implications for the transport and attenuation of indicator microorganisms and nitrogen down through the subsoils and into the groundwater. The results of this work have formed a large input into the production of a new Code of Practice Wastewater Treatment and Disposal Systems Serving Single Houses. This has led to changes in the design of on-site hydraulic loading from 180 L per capita per day (L/c.d) down to 150 L/c.d. The range of acceptable subsoils receiving septic tank effluent has narrowed for more highly permeable subsoils following a series of tracer studies using bacteriophages. However, the range has been extended for lower permeability subsoils (range 0.08 down to 0.06 m/d) receiving secondary treated effluent in order to encourage the effluent to spread further along the trenches. The maximum individual length of percolation trenches receiving secondary effluent has also been reduced to 10 m to encourage dispersion on a wider area. This paper thus highlights how research can directly feed into a Code of Practice. PMID- 22097046 TI - Mullite ceramic membranes for industrial oily wastewater treatment: experimental and neural network modeling. AB - In this paper, results of an experimental and modeling of separation of oil from industrial oily wastewaters (desalter unit effluent of Seraje, Ghom gas wells, Iran) with mullite ceramic membranes are presented. Mullite microfiltration symmetric membranes were synthesized from kaolin clay and alpha-alumina powder. The results show that the mullite ceramic membrane has a high total organic carbon and chemical oxygen demand rejection (94 and 89%, respectively), a low fouling resistance (30%) and a high final permeation flux (75 L/m2 h). Also, an artificial neural network, a predictive tool for tracking the inputs and outputs of a non-linear problem, is used to model the permeation flux decline during microfiltration of oily wastewater. The aim was to predict the permeation flux as a function of feed temperature, trans-membrane pressure, cross-flow velocity, oil concentration and filtration time, using a feed-forward neural network. Finally the structure of hidden layers and nodes in each layer with minimum error were reported leading to a 4-15 structure which demonstrated good agreement with the experimental measurements with an average error of less than 2%. PMID- 22097048 TI - Determination of perfluorinated compounds (PFCs) in solid and liquid phase river water samples in Chao Phraya River, Thailand. AB - Perfluorinated compounds (PFCs), especially perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are fully fluorinated organic compounds, which have been used in many industrial applications. These chemicals have contaminated surface water all over the world even in developing countries like Thailand. The previous study showed the contamination in Chao Phraya River in 2006 and 2007. The purposes of this field study were to determine the solid and liquid phase of PFCs contamination in Chao Phraya River and to compare the changes of PFC concentration in 2008. Surveys were conducted in the lower reach of Chao Phraya River in the industrialized area. A solid phase extraction (SPE) coupled with HPLC-ESI-MS/MS were used for the analysis for ten PFCs. Ten PFCs were analyzed to identify the contamination in both solid and liquid phases. PFCs were detected in both the solid and liquid phase in every sample. PFOA was the most dominant PFC while PFPA and PFOS were also highly detected in most samples. The average loadings of PFPA, PFOA and PFOS in Chao Phraya River were 94.3, 284.6 and 93.4 g/d, respectively. PFOS concentrations did not show differences between 2006 and 2008. However, PFOA concentrations were higher in 2008/5/26, while comparing other samplings. The ratio of solid:liquid PFPA (2.1:1.0) [(ng/g)/(ng/L)] was lower than PFOA (13.9:1.0) [(ng/g)/(ng/L)] and PFOS (17.6:1.0) [(ng/g)/(ng/L)]. The shorter chain (more hydrophilic) PFC was better to dissolve in water rather than adsorb onto suspended solids. PFOS also showed more potential to attach in the suspended solids than PFOA. PMID- 22097049 TI - Recovery of phosphorus and aluminium from sewage sludge ash by a new wet chemical elution process (SESAL-Phos-recovery process). AB - The potential of a new wet chemical process for phosphorus and aluminium recovery from sewage sludge ash by sequential elution with acidic and alkaline solutions has been investigated: SESAL-Phos (sequential elution of sewage sludge ash for aluminium and phosphorus recovery). Its most innovative aspect is an acidic pre treatment step in which calcium is leached from the sewage sludge ash. Thus the percentage of alkaline soluble aluminium phosphates is increased from 20 to 67%. This aluminium phosphate is then dissolved in alkali. Subsequently, the dissolved phosphorus is precipitated as calcium phosphate with low heavy metal content and recovered from the alkaline solution. Dissolved aluminium is recovered and may be reused as a precipitant in wastewater treatment plants. PMID- 22097050 TI - Full scale evaluation of diffuser ageing with clean water oxygen transfer tests. AB - Aeration is a crucial part of the biological wastewater treatment in activated sludge systems and the main energy user of WWTPs. Approximately 50 to 60% of the total energy consumption of a WWTP can be attributed to the aeration system. The performance of the aeration system, and in the case of fine bubble diffused aeration the diffuser performance, has a significant impact on the overall plant efficiency. This paper seeks to isolate the changes of the diffuser performance over time by eliminating all other influencing parameters like sludge retention time, surfactants and reactor layout. To achieve this, different diffusers have been installed and tested in parallel treatment trains in two WWTPs. The diffusers have been performance tested in clean water tests under new conditions and after one year of operation. A set of material property tests describing the diffuser membrane quality was also performed. The results showed a significant drop in the performance of the EPDM diffuser in the first year which resulted in similar oxygen transfer efficiency around 16 g/m3/m for all tested systems. Even though the tested silicone diffusers did not show a drop in performance they had a low efficiency in the initial tests. The material properties indicate that the EPDM performance loss is partly due to the washout of additives. PMID- 22097051 TI - Chemical disinfection of Legionella in hot water systems biofilm: a pilot-scale 1 study. AB - Legionella bacteria encounter optimum growing conditions in hot water systems and cooling towers. A pilot-scale 1 unit was built in order to study the biofilm disinfection. It consisted of two identical loops, one used as a control and the other as a 'Test Loop'. A combination of a bio-detergent and a biocide (hydrogen peroxide + peracetic acid) was applied in the Test Loop three times under the same conditions at 100 and 1,000 mg/L with a contact time of 24 and 3-6 hours, respectively. Each treatment test was preceded by a three week period of biofilm re-colonization. Initial concentrations of culturable Legionella into biofilm were close to 10(3) CFU/cm2. Results showed that culturable Legionella spp. in biofilm were no longer detectable three days following each treatment. evertheless, initial Legionella spp. concentrations were recovered 7 days after the treatments (in two cases). Before the tests, Legionella spp. and L. pneumophila PCR counts were both about 10(4) GU/cm2 in biofilm and they both decreased by 1 to 2 log units 72 hours after each treatment. The three tests had a good but transient efficiency on Legionella disinfection in biofilm. PMID- 22097052 TI - Two-phase thermophilic anaerobic digestion process for biohythane production treating biowaste: preliminary results. AB - This paper deals with the optimization of a two-phase anaerobic process treating biowaste for hydrogen and methane production. Neither physical nor chemical pre treatments were used to optimize the process. The work was carried out at pilot scale, using two CSTRs (200 and 380 L working volume respectively) both maintained at thermophilic temperature (55 C) and fed semi-continuously with biowaste. The experiment was divided into three periods; during the first two periods the organic loading rate was maintained at 20 kg TVS/m3 d and the hydraulic retention time was changed from 6.6 to 3.3 days, while in the last period the digestate of the second reactor was recirculated to the first reactor in order to buffer the system and control pH at levels around 5. The HRT was maintained at 3.3 days and the OLR was decreased at 16.5 kg TVS/m3 d. The best yield was obtained in the last period where a specific hydrogen production of 50.9 L/kg VSfed was reached, with a H2 content in biogas from the first reactor of 36%. The methanogenic stage after the hydrogen conversion reached a specific biogas production of 0.62 m3/kg VSfed and an overall organic removal above 70%, without any stability problem. The overall biogas production was some 1.5 m3 per day with a gas composition of 10% H2 and 50% CH4. PMID- 22097053 TI - Climate adaptive urban planning and design with water in Dutch polders. AB - The existing water management in Dutch polders is based on independent water systems for each polder. These are featuring artificial stabilized ground and surface water levels. As a result of the local climate the water levels in the polders are not continuously at a constant level. To maintain a stable water table in the polders, the surplus of relatively clean rainwater has to be pumped away during the cold seasons into canals or rivers, which are located on a higher level. During the summer relatively polluted water from these waterways is led into the polders to top up the declining water levels. This procedure leads to various problems regarding water quantity and water quality. The described existing system is not adaptable to climate change and includes the risk of flooding, particularly from torrential rain. Therefore it is crucial to develop, preferably self-sufficient, rainwater management systems in the polders. They should allow the fluctuation of the water levels inside the polders for seasonal storage and flood control. The described concept is adopted in the present water policy in the Netherlands as well as in research and recent urban development projects in Dutch polders. PMID- 22097054 TI - Characterization and kinetics of sulfide-oxidizing autotrophic denitrification in batch reactors containing suspended and immobilized cells. AB - Sulfide-oxidizing autotrophic denitrification is an advantageous alternative over heterotrophic denitrification, and may have potential for nitrogen removal of low strength wastewaters, such as anaerobically pre-treated domestic sewage. This study evaluated the fundamentals and kinetics of this process in batch reactors containing suspended and immobilized cells. Batch tests were performed for different NOx-/S2- ratios and using nitrate and nitrite as electron acceptors. Autotrophic denitrification was observed for both electron acceptors, and NOx-/S2 ratios defined whether sulfide oxidation was complete or not. Kinetic parameter values obtained for nitrate were higher than for nitrite as electron acceptor. Zero-order models were better adjusted to profiles obtained for suspended cell reactors, whereas first-order models were more adequate for immobilized cell reactors. However, in the latter, mass transfer physical phenomena had a significant effect on kinetics based on biochemical reactions. Results showed that sulfide-oxidizing autotrophic denitrification can be successfully established for low-strength wastewaters and have potential for nitrogen removal from anaerobically pre-treated domestic sewage. PMID- 22097055 TI - Acute toxicity and inactivation tests of CO2 on invertebrates in drinking water treatment systems. AB - In addition to the esthetic problem caused by invertebrates, researchers are recently starting to be more aware of their potential importance in terms of public health. However, the inactivation methods of invertebrates which could proliferate in drinking water treatment systems are not well developed. The objective of this study is to assess the acute toxicity and inactivation effects of CO2 on familiar invertebrates in water treatment processes. The results of this study revealed that CO2 has a definite toxicity to familiar invertebrates. The values of 24-h LC50 (median lethal concentration) were calculated for each test with six groups of invertebrates. The toxicity of CO2 was higher with increasing concentrations in solution but was lower with the increase in size of the invertebrates. Above the concentration of 1,000 mg/L for the CO2 solution, the 100% inactivation time of all the invertebrates was less than 5 s, and in 15 min, the inactivation ratio showed a gradient descent with a decline in concentration. As seen for Mesocyclops thermocyclopoides, by dosing with a sodium bicarbonate solution first and adding a dilute hydrochloric acid solution 5 min later, it is possible to obtain a satisfactory inactivation effect in the GAC (granular activated carbon) filters. PMID- 22097056 TI - Rapid quantification of polyhydroxyalkanoates (PHA) concentration in activated sludge with the fluorescent dye Nile blue A. AB - The present study was conducted (1) to develop a rapid quantification method of polyhydroxyalkanoates (PHA) concentration in activated sludge by Nile blue A staining and fluorescence measurement and (2) to perform on-line monitoring of PHA concentrations in activated sludge. Activated sludge samples collected from laboratory scale sequencing batch reactors and full-scale wastewater treatment plants were stained with Nile blue A and their fluorescence intensities were determined. There was a high correlation (R2 > 0.97) between the fluorescence intensities of Nile blue A and PHA concentrations in activated sludge determined by gas chromatography. The Nile blue A staining and fluorescence measurement method allows us to determine PHA concentrations in activated sludge within only five minutes and up to 96 samples can be measured at once by using microplate reader. On-line monitoring of PHA concentrations in activated sludge was achieved by using a fluorometer equipped with a flow cell and the time point at which PHA concentration in activated sludge reached the maximum level could be identified. In addition, we examined the influence of pH, floc size and co-existing chemicals in activated sludge suspension on the fluorescence intensities of Nile blue A. PMID- 22097057 TI - Decolorization of anthraquinone dye Reactive Blue 19 by the combination of persulfate and zero-valent iron. AB - Decolorization of anthraquinone dye Reactive Blue 19 (RB19) with sulfate radicals generated in situ from persulfate and zero-valent iron (ZVI) was investigated. The effects of initial solution pH, initial concentration of RB19, ZVI and persulfate, reaction temperature and common dissolved anions were studied. 100% color removal efficiency and 54% TOC removal efficiency were achieved in 45 min with an initial RB19 concentration of 0.1 mM under typical conditions (pH 7.0, 0.8 g L(-1) ZVI, 10 mM persulfate and 30 C). The decolorization efficiency of RB19 increased with higher iron dosage, higher initial persulfate concentration, and higher reaction temperature. It is also an acid driven process. The decolorization process followed pseudo-first order kinetics and the activation energy was 98.1 kJ mol-1. RB19 decolorization was inhibited by common dissolved anions such as CL-, NO3-, H2PO4- and HCO3- since they reacted with sulfate radicals that retarded the oxidation process. The experiment demonstrated that the combination of persulfate and ZVI was a promising technology for the decolorization of dye wastewater. PMID- 22097058 TI - Impact of operating history on mixed culture fermentation microbial ecology and product mixture. AB - Mixed culture fermentation is an alternative to pure culture fermentation for production of biofuels and valuable products. A glucose-fed, continuous reactor was operated cyclically to a central pH of 5.5 from a number of precedent pHs, from 4.5 to 7.5. At each pH, stable chemical production was reached after 2 retention times and was held for least 2 further retention times prior to the next change. Bacterial groups were identified by phylogenetic analysis of 16S rRNA gene clones. Bacterial community dynamics were monitored by terminal restriction fragment length polymorphism. More ethanol was produced at high pH, and more butyrate at lower pH. At pH 5.5, the product spectrum was not measurably influenced by precedent pH but showed seemingly random changes. The impact of precedent pH on community structure was more systematic, with clear indications that when the pH was returned to 5.5, the bacterial group that was dominant at the precedent pH remained at high abundance. This result is important, since it indicates a decoupling between microbial function (as indicated by product spectrum), and community structure. More work is needed to determine the longevity of this hysteresis effect. There was evidence that groups retained their ability to re-emerge even after times of low abundance. PMID- 22097059 TI - Storm water infiltration in a monitored green roof for hydrologic restoration. AB - The objectives of this study are to provide detailed information about green roof performance in the Mediterranean climate (retained volume, peak flow reduction, runoff delay) and to identify a suitable modelling approach for describing the associated hydrologic response. Data collected during a 13-month monitoring campaign and a seasonal monitoring campaign (September-December 2008) at the green roof experimental site of the University of Genova (Italy) are presented together with results obtained in quantifying the green roof hydrologic performance. In order to examine the green roof hydrologic response, the SWMS_2D model, that solves the Richards' equation for two-dimensional saturated unsaturated water flow, has been implemented. Modelling results confirm the suitability of the SWMS_2D model to properly describe the hydrologic response of the green roofs. The model adequately reproduces the hydrographs; furthermore, the predicted soil water content profile generally matches the observed values along a vertical profile where measurements are available. PMID- 22097060 TI - Process-based modelling of phosphorus removal in a novel constructed wetland system using dewatered alum-sludge as substrate. AB - A process-based model that can evaluate the transport and the fate of phosphorus (P) in agricultural wastewater was developed for a novel 4-stage dewatered alum sludge cakes (DASC) based constructed wetlands (CWs) system using STELLA software (version 9.1.4). The model considered adsorption, plant and microbial uptakes as the major forms of P involved in the transformation chains. The results were obtained by experimental procedure through laboratory measurement, from literature and/or calibration. The observed effluent P concentration in the CWs ranged from 3.62 to 8.50 mg/L (stage 1), 2.00 to 4.45 mg/L (stage 2), 1.39 to 3.76 mg/L (stage 3) and 0.52 to 2.36 mg/L (stage 4), whereas the simulated values ranged from 2.12 to 10.99 mg/L (stage 1), 1.32 to 5.65 mg/L (stage 2), 0.84 to 3.64 mg/L (stage 3) and 0.53 to 2.25 mg/L (stage 4), respectively. The simulated and observed values of P removal in the CWs system were in good agreement. A mass balance analysis was performed for all the major processes which resulted in a major pathway of P removal through adsorption (64-75%, 58-66%, 57-63% and 49-58%) followed by plant uptake (7-11%, 8-14%, 14-17% and 9-19%) and microbial uptake (3 7%, 3-5%, 9-12% and 7-12%) for stage 1, stage 2, stage 3 and stage 4, respectively. Thus the mathematical model developed in this study could be used to explain the removal processes and simulate the fate of P in the DASC-based CWS system. PMID- 22097061 TI - Security through diversity: moving from rhetoric to practice. AB - In response to a range of contemporary urban water challenges, there is an increasingly urgent need to change the way water is used in our cities. In Australia, the 'Security through Diversity' policy has been introduced in a number of cities to help facilitate a shift towards sustainable urban water management. This qualitative case study research investigated the interpretation and implementation of this radically different urban water policy approach across the case study cities of Perth and Melbourne. To focus the research and allow for more reliable comparative analysis across the cities, the introduction of desalination and permanent water saving rules as new initiatives in these cities were of particular interest. The research results are drawn from a synthesis of over 65 semi-structured interviews with senior urban water practitioners in the case study cities, and a content analysis of key policy and guidance documents, as well as organizational literature where available. The key finding of this research was that because of an entrenched technological paradigm, and the difficulty in breaking this pattern of lock-in, practitioners are currently interpreting and implementing Security through Diversity in a way that does not fully realise the potential of this strategy. More specifically the interview results revealed that the urban water practitioner community believed that the introduction of seawater desalination would discharge their city's responsibility for achieving Security through Diversity and that demand management initiatives, while nice, are not essential to this policy position. Interestingly, despite context evidence to the contrary, the practitioners believed supply and demand planning to be an integrated practice within their city. The paper concludes by offering some recommendations to facilitate a more comprehensive implementation of Security through Diversity and outlines areas for possible future research. PMID- 22097062 TI - Acidogenic fermentation of municipal solid waste and its application to bio electricity production via microbial fuel cells (MfCs). AB - Acidogenic fermentation of organic municipal solid waste (MSW) and the bio electricity production potential from its volatile fatty acid (VFA)-rich leachate using an air-cathode microbial fuel cell (MFC) was investigated in this study. The acidogenic fermentation of 2 kg of MSW has been carried out in a 6 L anaerobic leach-bed reactor (LBR) under mesophilic conditions (30 degrees C). Total production of 92 g VFA expressed as chemical oxygen demand (COD) in 3 L leachate mainly containing acetic, propionic, butyric, and valeric acids has been achieved with manual leachate recirculation and without pH control in 74 days of incubation. Leachate collected on day 32 was used as a feed to an air-cathode MFC after being diluted and supplemented with NaCl or NaHCO3. The maximum power density in the diluted leachate was only 5.9 W/m3, but reached up to 8.6 W/m3 upon the addition of 7 mmol/L NaCl. Increase in coulombic efficiency from 6 to 22% was also observed as a result of NaCl supplementation. On the other hand, NaHCO3 addition did not improve the power output. PMID- 22097064 TI - Determination of toxic heavy metals in sea water by FAAS after preconcentration with a novel chelating resin. AB - A solid phase extraction procedure was developed for preconcentration of toxic heavy metals such as cadmium, cobalt, copper, manganese, lead and zinc in sea water samples. A microcolumn packed with 6-[(4-hydroxyphenyl)diazenyl]naphthalene 2,3-diol-formaldehyde (HPDN-F) resin acts as a sorbent to retain the analyte ions by forming metal chelates. The retained trace level metal was subsequently eluted with 1 mol/L HCl and the acid eluent was analysed by Flame Atomic Absorption Spectrophotometer (FAAS). The HPDN-F chelating resin and its metal chelates were characterized by spectral and thermal analysis. The chelating property of the HPDN-F resin towards divalent metal ions was studied as a function of pH and preconcentration flow rate. The recoveries of cadmium, cobalt, copper, manganese, lead and zinc under the optimum working conditions were above 95%. The relative standard deviations were < 2%. The limits of detection were < 0.1 microg/L. The method presented was applied for the determination of cadmium, cobalt, copper, manganese, lead and zinc in sea water samples. PMID- 22097063 TI - Post-treatment of biologically treated wastewater of agrochemical industry by sulfated chitosan composite nanofiltration membrane. AB - The objective of this study is to treat the biologically treated wastewater using sulfated chitosan/ polyacrylonitrile (PAN) composite nanofiltration (NF) membrane to improve agrochemical industry wastewater quality for reuse. Although biological treatment is quite efficient, the wastewater does not meet the reuse criteria. Hence, further treatment to improve the water quality is investigated. Sulfated chitosan composite NF membranes, having a PAN ultrafiltration membrane as the substrate, are prepared by coating and cross-linking methods. The effects of membrane preparation conditions on the rejection and permeation performance of the membranes are studied. The new membranes are characterized by NMR and scanning electron micrograph. Wastewater from agrochemical industry contains high concentrations of organic matter, color, heavy metals and other toxic substances. The operating variables studied are applied pressure (3-15 atm) and feed flowrate (4-16 L/min). It is found that the observed rejection (R(o)) increases with increase in feed pressure at constant feed flowrate. The rejection of cations follows the sequence: R(o)(Zn2+) > R(o)(Ni2+) > R(o)(CU2+) > R(o)(Cd2+) for wastewater. It is observed that the order of solute rejection sequence is inversely proportional to the diffusion coefficients. PMID- 22097065 TI - Determination of processes affecting groundwater quality in the coastal aquifer beneath Puri city, India: a multivariate statistical approach. AB - Variability of groundwater quality parameters is linked to various processes such as weathering, organic matter degradation, aerobic respiration, iron reduction, mineral dissolution and precipitation, cation exchange and mixing of salt water with fresh water. Multivariate statistical analyses such as principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied to the standardized data set of eleven groundwater quality parameters (i.e. pH, Ca2+, Mg2+, Na+, K+, Fe3+, alkalinity, NO3-, Cl-, SO4(2-), TDS) collected during the post-monsoon and the summer seasons in order to elicit hydrologic and biogeochemical processes affecting water quality in the unconfined aquifer beneath Puri city in eastern India. The application of PCA resulted in four factors explaining 73% variance in post-monsoon and 81% variance in summer. The HCA using Ward's method and squared Euclidean distance measure classified the parameters into four clusters based on their similarities. PCA and HCA allowed interpretation of processes. During both post-monsoon and summer seasons, anthropogenic pollution and organic matter degradation/Fe(III) reduction were found dominant due to contribution from on-site sanitation in septic tanks and soak pits in the city. Cation exchange and mineral precipitation were possible causes for increase in Na+ and decrease in Ca2+ concentration in summer. Fresh water recharge during monsoon and Sea water intrusion in summer are attributed as significant hydrologic processes to variations of the groundwater quality at the study site. PMID- 22097066 TI - Elimination and accumulation of polycyclic aromatic hydrocarbons in urban stormwater wet detention ponds. AB - The concentrations of polycyclic aromatic hydrocarbons (PAHS) in water and sediments of seven wet detention ponds receiving urban stormwater were investigated. The ponds comprised traditional wet detention ponds with a permanent wet volume and a storage volume as well as ponds that were expanded with sand filters and other means to improve the removal of micropollutants. The concentrations of sigmaPAH in the sediments varied between 6 +/- 5 and 2,222 +/- 603 ng g(-1) dry weight (mean +/- standard deviation), and were highest in the ponds with lower pond volume per catchment area and did not clearly reflect different activities in the catchments. In general, the concentrations of PAHS in the sediments decreased from inlet to outlet, especially in the systems with good conditions for sedimentation such as systems with flow perpendicular sand dikes and extensive submerged vegetation. High molecular weight PAHs were predominant in the sediments indicating the pyrogenic origin of the PAHS. There was no correlation between PAH species concentrations in water or sediments and their hydrophobicity (log K(ow)). PAH concentrations in water fluctuated in response to intensity and frequency of rain events, whereas concentrations in the sediments integrated the pollutant load over time. Pond systems expanded with sand filters and other technologies to enhance removal of micropollutants consistently had concentrations of PAHS in the effluents below the detection level. PMID- 22097067 TI - Total and hexavalent chromium removal in a subsurface horizontal flow (h-SSF) constructed wetland operating as post-treatment of textile wastewater for water reuse. AB - In this study we investigated total and hexavalent chromium removal in an h-SSF constructed wetland (CW) planted with Phragmites australis and operating as post treatment of effluent wastewater from an activated sludge plant serving the textile industrial district of Prato (Italy). Two measurement campaigns were carried out in 2006 and 2008-2010 in which more than 950 inlet and outlet samples were analyzed. When inlet and outlet concentrations were compared one to the other, the latter were found to be significantly lower than the former (p < 0.001); during the entire period of investigation, removal of hexavalent chromium equal to about 70% was achieved. Outlet concentrations ranged between values lower than the quantification limit (0.5 microg L(-1)) and 4.5 microg L(-1), and in all cases were therefore lower than the limit indicated for hexavalent chromium in the Italian regulation for water reuse (5 microg L(-1)). The comparison of the removal efficiencies achieved for hexavalent and trivalent chromium during the two campaigns suggested that the removal of the former can be sustained in the long term, while for the latter, the treatment efficiency is more sensitive to the age of the CW, being that it is it based on trivalent chromium retention in the reed bed. PMID- 22097068 TI - Urban flood risk assessment using sewer flooding databases. AB - Sustainable water management is a global challenge for the 21st century. One key aspect remains protection against urban flooding. The main objective is to ensure or maintain an adequate level of service for all inhabitants. However, level of service is still difficult to assess and the high-risk locations difficult to identify. In this article, we propose a methodology, which (i) allows water managers to measure the service provided by the urban drainage system with regard to protection against urban flooding; and (ii) helps stakeholders to determine effective strategies for improving the service provided. One key aspect of this work is to use a database of sewer flood event records to assess flood risk. Our methodology helps urban water managers to assess the risk of sewer flooding; this approach does not seek to predict flooding but rather to inform decision makers on the current level of risk and on actions which need to be taken to reduce the risk. This work is based on a comprehensive definition of risk, including territorial vulnerability and perceptions of urban water stakeholders. This paper presents the results and the methodological contributions from implementing the methodology on two case studies: the cities of Lyon and Mulhouse. PMID- 22097069 TI - Comparison of the photoconversion of para-chlorophenol under simulated sunlight and UV irradiation in ice. AB - The photochemistry of para-chlorophenol (4-CP) was studied under simulated sunlight (lambda > 300 nm) and UV irradiation by using a 125 W high-pressure mercury lamp with or without a hard glass as light source in an ice matrix. The experiments were carried out in a photochemical cold chamber reactor at -14 to 12 degrees C. The photoconversion rate, photoproducts and photoconversion mechanism of 4-CP were all inspected and compared. The results show that the 4-CP photoconversion obeys the first order kinetic model and its photoconversion rate is highly affected by the initial concentration of 4-CP, light intensity and water quality. It is found that the conversion rate of 4-CP under UV irradiation is higher than that under simulated sunlight irradiation. The intermediate products of 4-CP were characterized by GC-MS, HPLC-ESI-MS and HPLC techniques and the possible photoconversion mechanism was proposed accordingly. It is concluded that the mechanism and photoproducts of 4-CP photolysis in ice are different from those in water, and the photoproducts and photoconversion pathways of 4-CP in ice varied with different light sources. PMID- 22097070 TI - Relative kinetics of anaerobic digestion under thermophilic and mesophilic conditions. AB - With several advantages over the conventional mesophilic anaerobic digestion, such as better sludge quality and higher biogas production, thermophilic anaerobic digestion is regarded as a promising alternative for sludge digestion. Primary and activated sludges are complex materials, and historically, analysis of kinetics has been largely on whole sludge, without analysis of individual components. This paper analyses relative digestion kinetics of pure substrates designed to target main stages of sludge digestion under thermophilic and mesophilic conditions. Hydrolysis rate of cellulose was significantly influenced by temperature with hydrolysis coefficients of--at 55 degrees C (0.7 +/- 0.1 day( 1)), 60 degrees C (0.8 +/- 0.2 day(-1)), 65 degrees C (1.1 +/- 0.2 day(-1)) and 70 degrees C (1.2 +/- 0.2 day(-1)) over 38 degrees C (0.4 +/- 0.1 day(-1)). This strongly follows the Arrhenius relationship, with an activation energy (E(A)) of 31 +/- 4 kJ mol(-1), corresponding to an increase of 1.5x for each 10 degrees C of temperature increase. Glucose uptake was rapid with a wide variety of fermentation products detected under mesophilic conditions, while uptake was slower under thermophilic conditions with acetate and propionate being dominant products. Propionate acetogenesis and acetate-utilizing methanogenesis kinetics were not influenced by temperatures. Hydrolysis is widely regarded as a rate limiting step in sludge digestion, thus improvements in hydrolysis rates as measured during this study have the potential for significant improvements in overall apparent sludge digestion rates. PMID- 22097071 TI - Membrane treatment of liquid wastes from radiological decontamination operations. AB - The paper focuses on the evaluation of membrane filtration for the treatment of liquid radioactive streams generated in area decontamination operations. In this work, semi-permeable membranes were demonstrated to be effective reducing the volume of wastewater containing cesium and cobalt by two orders of a magnitude. The efficiency of membrane separation was enhanced by employing additives that enlarged the size of target radionuclide species and improved their rejection by the membranes. This was achieved by chelation with synthetic water-soluble polymers and by adsorption on micro particles of adsorbent coupled with micelle formation. The effect of wastewater composition and that of the radionuclide binding additives on the volume reduction was investigated. Membrane treatment is expected to help simplify further processing and decrease disposal costs. PMID- 22097072 TI - GIS and ordination techniques for studying influence of watershed characteristics on river water quality. AB - Landscape characteristics of twenty-eight sub-catchments within the Miyun reservoir watershed in Miyun County, northeast Beijing of China were examined to identify relationships with stream water chemistry. The influences of the entire catchment and 300 m buffer zone on water quality were compared using multiple regression analysis and redundancy analysis during three seasons. Results showed that strong seasonal differences in nitrate, nitrite and ammonium are observed whereas no difference in total phosphorus and conductivity. Landscape factors were significantly correlated to stream water quality. Residential area and stream density contributed markedly to river condition variability. Water quality was better explained by interactions with the landscape during and after rainy season. There was also a seasonal shift in the landscape factors that were the dominant explanatory variables. The relationships between landscape attributes and water quality on watershed scale were slightly different from those on riparian scale; however, landscape attributes may have stronger influences on water chemistry. PMID- 22097073 TI - Reuse of treated wastewater and sewage sludge for fertilization and irrigation. AB - The objective of the present work was to assess the short-term potential of treated wastewater and sewage sludge for ornamental lawn fertilization and irrigation. A field experiment was performed and the following treatments were considered: sewage sludge application + irrigation with public water; sewage sludge application + irrigation with treated wastewater; irrigation with public water; irrigation with treated wastewater (TW). Irrigation with treated wastewater showed a positive effect on lawn installation through higher growth of grass (1,667 cm) and higher dry matter yield (18,147 g m(-2)). These results represent a significant increase in the grass yield compared with public water irrigation. The grass height (2,606 cm) and dry matter yield (23,177 g m(-2)) increased even more, when sewage sludge produced in the wastewater treatment plant (WWTP) was applied to soil, which proves once more its benefits as an organic fertilizer. At the end of the experiment, an increase of some soil parameters (pH, electrical conductivity, organic matter, Ca2+, Na+, K+, Mg2+ and NH4+) was observed, indicating that treated wastewater irrigation can cause a soil sodization. This short-term study indicated that use of treated wastewater and sewage sludge for ornamental lawn fertilization and irrigation is an environmentally sustainable option for re-use of the WWTP by-products. PMID- 22097074 TI - Assessing the role of biochemical methane potential tests in determining anaerobic degradability rate and extent. AB - The biodegradability and bioavailability of hydrolysis-limited substrates under anaerobic (and aerobic) conditions can be represented by two key parameters- degradability (f(d)), or the percentage that can be effectively be destroyed during digestion, and first order hydrolysis coefficient (k(hyd)), or the speed at which material breaks down. Biochemical methane potential (BMP) testing uses a batch test (in triplicate), and by fitting against a first order model, can fit both parameters in the same test. BMP testing is now being widely used for anaerobic process feasibility and design purposes, and standardisation efforts are ongoing. In this paper, we address a number of key issues relating to the test method and its analysis. This includes proposal of a new fitting and parameter estimation method, evaluation of the impact of inoculum to substrate ratio on fitted parameters, and comparison to performance in continuous systems. The new parameter estimation technique provides an estimate of parameter uncertainty and correlation, and is clearly more suitable than model transformation and linear regression. An inoculum volume ratio of at least 50% (2:1 on VS basis) was required on a cellulose substrate to use methane production as primary indicator, as found by comparing methane production and solubilisation of cellulose. Finally, on a typical material, waste activated sludge, the batch test was slightly conservative in terms of degradability and rate, indicating a bias in the BMP test. The test is a cost-effective and capable method to evaluate potential substrates, but it should be noted that it is generally conservative, especially if sub-optimal inoculum is used. PMID- 22097075 TI - Effect of phosphorus concentration on phosphorus removal and biomass. AB - Membrane bioreactor (MBR) process was employed to study the effect of biological phosphorus removal (bio-P removal) and P-content in treated sludge with increased phosphorus concentration present in the wastewater. Further, the following four test fractions of raw wastewaters was obtained having different P-concentrations viz., run 1: P-20 mg/L, run 2: P-40 mg/L, run 3: P-60 mg/L, run 4: P-80 mg/L. The effective P-removal obtained for these four test fractions were found to be 23.07 mg/L (98.17%), 41.35 mg/L (88.16%), 45.75 mg/L (72.04%) and 55.80 mg/L (66.82%) respectively for run 1, 2, 3 and 4 fractions. Moreover, the similar increase in phosphorous concentration i.e., from 20 to 80 mg/L caused an apparent increase in total solid (TS) values from 7 to 8.3 g TS/L, whereas the total volatile solid (TVS) content remained constant (i.e. 4.5 g TVS/L). These results inferred that the proportion of TVS in the TS decreased from 70 to 55%. Moreover, by increasing the initial P-concentration from 20 to 80 mg/L, the corresponding P-proportion of excess sludge was increased from 2 to 6.2%. PMID- 22097076 TI - Development of a GIS method to localize critical source areas of diffuse nitrate pollution. AB - The present study aimed at developing a universal method for the localization of critical source areas (CSAs) of diffuse nitrate (NO3-) pollution in rural catchments with low data availability. Based on existing methods, land use, soil, slope, riparian buffer strips and distance to surface waters were identified as the most relevant indicator parameters for diffuse agricultural NO3- pollution. The five parameters were averaged in a GIS-overlay to localize areas with low, medium and high risk of NO3- pollution. A first application of the GIS approach to the Ic catchment in France, showed that identified CSAs were in good agreement with results from river monitoring and numerical modelling. Additionally, the GIS approach showed low sensitivity to single parameters, which makes it robust to varying data availability. As a result, the tested GIS-approach provides a promising, easy-to-use CSA identification concept, applicable for a wide range of rural catchments. PMID- 22097077 TI - Removal of methylene blue from water by gamma-MnO2. AB - Methylene blue (MB) is a cationic dyestuff, which is particularly resistant to biodegradation. The molecular sieved gamma-MnO2 was used as an adsorbent/oxidant to remove the MB at room temperature and in visible light. The removal efficiency was mainly evaluated by X-ray diffractometer (XRD), UV-Vis spectrometer (UV-Vis), total organic carbon (TOC). The results revealed that the mechanisms of MB removal by gamma-MnO2 are significantly influenced by the pH. In acidic conditions, hypsochromic effects (i.e. blue shifts of UV-Vis spectra) resulting from N-demethylation of the dimethylamino group in MB may occur concomitantly with oxidative degradation by gamma-MnO2. However, the TOC in solution after gamma-MnO2 treatment in acidic conditions did not show a dramatic decrease. At near neutral pH conditions, there was almost no UV-Vis absorption for the MB solution, however, only 50% TOC removal was observed. It indicated that MB was not only adsorbed onto gamma-MnO2 but also partially oxidatively degraded to other organic compounds which were colourless for UV-Vis. PMID- 22097078 TI - Simultaneous domestic wastewater treatment and renewable energy production using microbial fuel cells (MFCs). AB - Microbial fuel cells (MFCS) can be used in wastewater treatment and to simultaneously produce electricity (renewable energy). MFC technology has already been applied successfully in lab-scale studies to treat domestic wastewater, focussing on organic matter removal and energy production. However, domestic wastewater also contains nitrogen that needs to be treated before being discharged. The goal of this paper is to assess simultaneous domestic wastewater treatment and energy production using an air-cathode MFC, paying special attention to nitrogen compound transformations. An air-cathode MFC was designed and run treating 1.39 L d(-1) of wastewater with an organic load rate of 7.2 kg COD m(-3) d(-1) (80% removal efficiency) and producing 1.42 W m(-3). In terms of nitrogen transformations, the study demonstrates that two different processes took place in the MFC: physical-chemical and biological. Nitrogen loss was observed increasing in line with the power produced. A low level of oxygen was present in the anodic compartment, and ammonium was oxidised to nitrite and nitrate. PMID- 22097079 TI - Biofilm development during the start-up of a sulfate-reducing down-flow fluidized bed reactor at different COD/SO4(2-) ratios and HRT. AB - In sulfate-reducing reactors, it has been reported that the sulfate removal efficiency increases when the COD/SO4(2-) ratio is increased. The start-up of a down-flow fluidized bed reactor constitutes an important step to establish a microbial community in the biofilm able to survive under the operational bioreactor conditions in order to achieve effective removal of both sulfate and organic matter. In this work the influence of COD/SO4(2-) ratio and HRT in the development of a biofilm during reactor start-up (35 days) was studied. The reactor was inoculated with 1.6 g VSS/L of granular sludge, ground low density polyethylene was used as support material; the feed consisted of mineral medium at pH 5.5 containing 1 g COD/L (acetate:lactate, 70:30) and sodium sulfate. Four experiments were conducted at HRT of 1 or 2 days and COD/SO4(2-) ratio of 0.67 or 2.5. The results obtained indicated that a COD/SO4(2-) ratio of 2.5 and HRT 2 days allowed high sulfate and COD removal (66.1 and 69.8%, respectively), whereas maximum amount of attached biomass (1.9 g SVI/L support) and highest sulfate reducing biofilm activity (10.1 g COD-H2S/g VSS-d) was achieved at HRT of 1 day and at COD/sulfate ratios of 0.67 and 2.5, respectively, which suggests that suspended biomass also played a key role in the performance of the reactors. PMID- 22097080 TI - Effect of operating temperature on performance of microbial fuel cell. AB - The performance of dual chambered mediator-less microbial fuel cell (MFC) operated under batch mode was evaluated under different operating temperatures, ranging between 20 and 55 degrees C, with step increase in temperature of 5 degrees C. Synthetic wastewater with sucrose as carbon source having chemical oxygen demand (COD) of 519-555 mg/L was used in the study. Temperature was a crucial factor in the performance of MFCs for both COD removal and electricity production. The MFC demonstrated highest COD removal efficiency of 84% and power density normalized to the anode surface area of 34.38 mW/m2 at operating temperature of 40 degrees C. Higher VSS to SS ratio was observed at the operating temperature between 35 and 45 degrees C. Under different operating temperatures the observed sludge yield was in the range of 0.05 to 0.14 g VSS/g COD removed. The maximum Coulombic and energy efficiencies were obtained at 40 degrees C, with values of 7.39 and 13.14%, respectively. Internal resistance of the MFC decreased with increase in operating temperature. Maximum internal resistance of 1,150 omega was observed when the MFC was operated at 20 degrees C; whereas the minimum internal resistance (552 omega) was observed at 55 degrees C. PMID- 22097081 TI - Enhancement of a UASB-septic tank performance for decentralised treatment of strong domestic sewage. AB - The possibility of enhancing the process performance of the UASB-septic tank for treating strong sewage in Palestine by means of inoculating the reactor with well adapted anaerobic sludge and/or adding a packing media to the upper part of the reactor, creating an anaerobic hybrid (AH)-septic tank, was investigated. To achieve these objectives, two community onsite UASB-septic tank and AH-septic tank were operated in parallel at 2 days HRT for around 8 months overlapping the cold and hot periods of the year in Palestine. The achieved removal efficiencies of CODtot in the UASB-septic tank and AH-septic tank during the first months of operation, coinciding with the cold period and the subsequent hot period, were respectively 50 (+/- 15)% and 48 (+/- 15)% and 66 (+/- 8)% and 55 (+/- 8)%. This shows that the UASB-septic tank performed significantly better (p < 0.05) than the AH-septic tank after rather long periods of operation. The difference in the CODtot removal efficiency was mainly due to the better CODss removal efficiencies in the UASB-septic tank. The removal efficiencies over the last 50 days of operation for CODtot, CODsus, CODcol and CODdis were 70, 72, 77 and 55% and 53, 54, 78 and 45% for the UASB-septic tank and AH-septic tank, respectively. Comparing the here achieved COD removal efficiencies with previously reported efficiencies of UASB-septic tanks operated in Palestine shows that the reactor performance in terms of COD removal and conversion, during the first 8 months of operation, has improved substantially by being started with well adapted anaerobic sludge, simulating and predicting long-term performance. Adding packing media did not lead to an improvement. PMID- 22097082 TI - Systematic evaluation of biofilm models for engineering practice: components and critical assumptions. AB - Biofilm models are valuable tools for the design and evaluation of biofilm-based processes despite several uncertainties including the dynamics and rate of biofilm detachment, concentration gradients external to the biofilm surface, and undefined biofilm reactor model calibration protocol. The present investigation serves to (1) systematically evaluate critical biofilm model assumptions and components and (2) conduct a sensitivity analysis with the aim of identifying parameter subsets for biofilm reactor model calibration. AQUASIM was used to describe submerged-completely mixed combined carbon oxidation and nitrification IFAS and MBBR systems, and tertiary nitrification and denitrification MBBRs. The influence of uncertainties in model parameters on relevant model outputs was determined for simulated scenarios by means of a local sensitivity analysis. To obtain reasonable simulation results for partially penetrated biofilms that accumulated a substantial thickness in the modelled biofilm reactor (e.g. 1,000 microm), an appropriate biofilm discretization was applied to properly model soluble substrate concentration gradients and, consistent with the assumed mechanism for describing biofilm biomass distribution, biofilm biomass spatial variability. The MTBL thickness had a significant impact on model results for each of the modelled reactor configurations. Further research is needed to develop a mathematical description (empirical or otherwise) of the MTBL thickness that is relevant to modern biofilm reactors. No simple recommendations for a generally applicable calibration protocol are provided, but sensitivity analysis has been proven to be a powerful tool for the identification of highly sensitive parameter subsets for biofilm (reactor) model calibration. PMID- 22097083 TI - Critical source area management of agricultural phosphorus: experiences, challenges and opportunities. AB - The concept of critical source areas of phosphorus (P) loss produced by coinciding source and transport factors has been studied since the mid 1990s. It is widely recognized that identification of such areas has led to targeting of management strategies and conservation practices that more effectively mitigate P transfers from agricultural landscapes to surface waters. Such was the purpose of P Indices and more complex nonpoint source models. Despite their widespread adoption across the U.S., a lack of water quality improvement in certain areas (e.g. Chesapeake Bay Watershed and some of its tributaries) has challenged critical source area management to be more restrictive. While the role of soil and applied P has been easy to define and quantify, representation of transport processes still remains more elusive. Even so, the release of P from land management and in-stream buffering contribute to a legacy effect that can overwhelm the benefits of critical source area management, particularly as scale increases (e.g. the Chesapeake Bay). Also, conservation tillage that reduces erosion can lead to vertical stratification of soil P and ultimately increased dissolved P loss. Clearly, complexities imparted by spatially variable landscapes, climate, and system response will require iterative monitoring and adaptation, to develop locally relevant solutions. To overcome the challenges we have outlined, critical source area management must involve development of a 'toolbox' that contains several approaches to address the underlying problem of localized excesses of P and provide both spatial and temporal management options. To a large extent, this may be facilitated with the use of GIS and digital elevation models. Irrespective of the tool used, however, there must be a two-way dialogue between science and policy to limit the softening of technically rigorous and politically difficult approaches to truly reducing P losses. PMID- 22097084 TI - Effect of thermal alkaline pretreatment on the anaerobic digestion of wasted activated sludge. AB - The effect of alkaline pretreatment of waste-activated sludge, using two models to study the sequential hydrolysis rates of suspended (Sanders' surface model) and dissolved (Goel's saturation model) solids, on the mesophilic and thermophilic anaerobic digestion rate is evaluated. The pretreatment, which reduces the size of the solids, increases the reaction rate by increasing the surface area and the specific surface hydrolysis constant (K(SBK)); at thermophilic conditions from 0.45 x 10(-3) kg m(-2) d(-1) for the fresh sludge to 0.74 x 10(-3) kg m(-2) d(-1) for the pretreated sludge and at mesophilic conditions these values are 0.28 x 10(-3) kg m(-2) d(-1) and 0.47 x 10(-3) kg m( 2) d(-1) confirming the usefulness of a pretreatment for solids reduction. But for soluble solids, the thermoalkaline pretreatment decreases the reaction rates by inducing a competitive inhibition on the thermophilic anaerobic digestion rate while in the mesophilic range, a non-competitive inhibition is observed. A mathematical simulation of the consecutive reactions, suspended solids to dissolved solids and to methane in staged anaerobic thermophilic-mesophilic digestion, shows that with 4% suspended solids concentration it is better not to use a thermoalkaline pretreatment because overall solids reduction and total methane production are not as good as without pretreatment. PMID- 22097085 TI - Degradation of organic dye using zero-valent iron prepared from by-product of pickling line. AB - In this study, zero-valent iron (ZVI) was produced using iron oxide that is a by product of a pickling line at a steel works. The reaction activity of the produced ZVI was evaluated through a series of decomposition experiments of Orange II aqueous solution. The size of ZVI particles increased with reduction temperature due to coalescence. Correspondingly, the specific surface area of ZVI decreased with increasing reduction temperature. The decomposition efficiency of synthesized ZVI particles was higher at a lower pH. In particular, no significant decomposition reaction was observed at pH of 4 and higher. The rate of the ZVI assisted decomposition of Orange II was increased by addition of H2O2 at pH of 3, whereas it was reduced by addition of H2O2 at a higher pH of 6. Nevertheless, simultaneous use of ZVI, UV and H2O2 led to a considerable increase in the decomposition rate even at a high pH condition (pH = 6). PMID- 22097086 TI - Effect of hydraulic retention time on pretreatment of blended municipal sludge. AB - The objective of the present work was to evaluate the effect of hydraulic retention time (HRT) on hydrolysis and acidogenesis for the pretreatment processes: acid phase digestion (APD) and autothermal thermophilic aerobic digestion (ATAD) using blended municipal sludge. The effect of the different pretreatment steps on mesophilic anaerobic digestion (MAD) was evaluated in terms of methane yield, keeping the operating conditions of the MAD the same for all systems. Best operating conditions for both APD and ATAD were observed for 2.5 d HRT with high total volatile fatty acids (tVFA), and the highest methane yield observed for MAD. No significant difference was observed between the two processes in terms of overall volatile solids (VS) reduction with same total HRT. The autothermal process produced heat of 14,300 J/g VS removed from hydrolytic and acetogenic reactions without compromising overall methane yields when the HRT was 2.5 d or lower and the total O2 used was 0.10 m3 O2/g VS added or lower. However, the process needs the input of oxygen and engineering analysis should balance these differences when considering the relative merits of the two pretreatment processes. This is the first study of its kind directly comparing these two viable pretreatment processes with the same sludge. PMID- 22097087 TI - Evaluation of undersized bioretention stormwater control measures for treatment of highway bridge deck runoff. AB - Two grassed bioretention cells were constructed in the easement of a bridge deck in Knightdale, North Carolina, USA, in October, 2009. One was intentionally undersized ('small'), while the other was full sized ('large') per current North Carolina standards. The large and small cells captured runoff from the 25- and 8 mm events, respectively. Both bioretention cells employed average fill media depths of 0.65 m and internal water storage (IWS) zones of 0.6 m. Flow proportional, composite water quality samples were collected and analyzed for nitrogen species, phosphorus species, and TSS. During 13 months of data collection, the large cell's median effluent concentrations and loads were less than those from the small cell. The small cell's TN and TSS load reductions were 84 and 50%, respectively, of those achieved by the large cell, with both cells significantly reducing TN and TSS. TP loads were not significantly reduced by either cell, likely due to low TP concentrations in the highway runoff which may have approached irreducible levels. Outflow pollutant loads from the large and small cell were not significantly different from one another for any of the examined pollutants. The small cell's relative performance provides support for retrofitting undersized systems in urbanized areas where there is insufficient space available for conventional full-sized stormwater treatment systems. PMID- 22097088 TI - Pollutant removal in a multi-stage municipal wastewater treatment system comprised of constructed wetlands and a maturation pond, in a temperate climate. AB - A multi-stage municipal wastewater treatment system is proposed to comply with Mexican standards for discharge into receiving water bodies. The system is located in Santa Fe de la Laguna, Mexico, an area with a temperate climate. It was designed for 2,700 people equivalent (259.2 m3/d) and consists of a preliminary treatment, a septic tank as well as two modules operating in parallel, each consisting of a horizontal subsurface-flow wetland, a maturation pond and a vertical flow polishing wetland. After two years of operation, on-site research was performed. An efficient biochemical oxygen demand (BOD5) (94-98%), chemical oxygen demand (91-93%), total suspended solids (93-97%), total Kjeldahl nitrogen (56-88%) and fecal coliform (4-5 logs) removal was obtained. Significant phosphorus removal was not accomplished in this study (25-52%). Evapotranspiration was measured in different treatment units. This study demonstrates that during the dry season wastewater treatment by this multi-stage system cannot comply with the limits established by Mexican standards for receiving water bodies type 'C'. However, it has demonstrated the system's potential for less restrictive uses such as agricultural irrigation, recreation and provides the opportunity for wastewater treatment in rural areas without electric energy. PMID- 22097089 TI - Experimental design of diffusion and desorption of contaminant in heterogeneous media. AB - Storage of contaminants in low permeability media (LPM) presents a great challenge for prediction of remediation effectiveness and efficiency. The reason lies in the contaminants' complex behaviors within heterogeneous media. Both interparticle and intraparticle diffusion contribute to the difficulty of precise site assessment. Sorption of contaminants--especially within LPM--may sequester the contaminants from active treatment, while desorption over a long period of time leads to contaminant release from storage and consequent re-contamination. Research has been conducted toward better understanding of contaminant diffusion and sorption/desorption processes to better predict contaminant response to site treatment. However, most of the research has been carried out within homogeneous media, while real scenarios in environmental problems feature media whose permeability and other characteristics vary significantly over the treatment volume. Further, few efforts have combined the interparticle/intraparticle diffusion and sorption/desorption processes together. This research aims at a feasible experimental design of diffusion and desorption of contaminant in heterogeneous media to address the gaps in previous research. A 2-D experimental system was designed to evaluate interparticle/intraparticle diffusion processes of trichloroethylene (TCE) in heterogeneous media. The 2-D system was modified to include organic matter in media for simulation of sorption/desorption processes. Results of the research will improve the understanding of how these different transport processes act together within heterogeneous media. Results will also allow for the evaluation of the impact of contaminant mass transport from within low permeability media at a potential treatment site and can support the development of mathematical tools/models combining interparticle/intraparticle and sorption/desorption processes. Such a model will promote more accurate site assessment and provide more confidence in the choice of an effective, economically optimized remediation strategy. PMID- 22097090 TI - Application of flow cytometry for examining phytoplankton succession in two eutrophic lakes. AB - Flow cytometry has potential as a rapid assessment technique to evaluate phytoplankton biomass and species composition. It facilitates for multi-parameter analysis of individual cells on the basis of light scattering effects induced from cellular constituents, as well as auto-fluorescence. Fluorescence emission characteristics may be especially useful in classifying cyanobacteria as they contain phycoerythrin which emits light predominantly in the 550-600 nm waveband, chlorophyll-a (650-700 nm emission) and allophycocyanin (660 nm emission). The objective of our study was to assess the utility of flow cytometry for the rapid identification and sorting of freshwater algae and cyanobacteria species. Using a selection of laboratory-cultured freshwater algae and cyanobacteria species, this study demonstrated unique light scatter and fluorescent characteristics for each species examined, allowing for rapid species identification and sorting of mixed populations of laboratory cultures and samples from two lakes in the Rotorua region (New Zealand). Analysis of lake water samples collected over seven months demonstrated changes in abundance and community composition of phytoplankton in the two lakes and demonstrates that flow cytometry may be a useful technique for examining seasonal changes in phytoplankton composition. PMID- 22097091 TI - Assessing sub-Saharan Erythrina for efficacy: traditional uses, biological activities and phytochemistry. AB - The genus Erythrina comprises more than 100 species, widely distributed in tropical and subtropical areas. In Africa, 31 wild species and 14 cultivated species have been described. In sub-Saharan Africa, Erythrina species are used to treat frequent parasitic and microbial diseases, inflammation, cancer, wounds. The rationale of these traditional uses in African traditional medicine was established by screening several species for biological activities. Promising activities were found against bacteria, parasites (Plasmodium), human and phytopathogenic fungi, some of which were multidrug resistant (MDR) micro organisms. Some species also exhibited antioxidant, anti-inflammatory activities and enzymes inhibitory properties. Most of the species chemically investigated were reported to contain flavanones, prenylated isoflavones, isoflavanones and pterocarpans. Some phytochemicals (vogelin B, vogelin C, isowightcone, abyssinin II, derrone) were the active principles as antibacterials, antifungals, antiplasmodials and inhibitors of enzyme borne diseases (PTP1B, HIV protease, DGAT). This review highlights the important role of Erythrina species as sources of lead compounds or new class of phytotherapeutic agents for fighting against major public health (MDR infections, cancer, diabetes, obesity) in sub-Saharan Africa. PMID- 22097092 TI - Comparison of ketamine and fentanyl for postoperative pain relief in children following adenotonsillectomy. AB - Adenotonsillectomy has a high incidence of postoperative pain. Therefore, the purpose of this study was to evaluate the effectiveness and safety of either ketamine or fentanyl for postoperative pain relief in children following adenotonsillectomy. Sixty children aged 3-12 years, scheduled for adenotonsillectomy, were enrolled in this randomized, double-blind study. Patients were divided into two groups of 30 cases and received intravenous ketamine (0.5 mg kg(-1)) or fentanyl (1 microg kg(-1)). Modified Hannallah pain scale or Observational Pain Scores (OPS), nausea, vomiting, bleeding, rescue analgesia, sedation and post-anesthesia recovery scores were recorded both at first and 15th minute postoperatively. Moreover, patients receiving ketamine (group 1) or fentanyl (group 2) had comparable OPS and sedation score both on arrival and at 15th minute in the recovery room (p > 0.05). Although rescue analgesics were similarly required in both groups (p > 0.05), the time to reach rescue analgesia was shorter in group 1 (p = 0.001). Only one patient in fentanyl group had nausea and vomiting in the first 15 min that needed antiemetic in the recovery room. In conclusion, intravenous fentanyl (1 microg kg(-1)) compared with intravenous ketamine (0.5 mg kg(-1)) might provide extended time to first analgesic in children undergoing adenotonsillectomy. Interestingly, fentanyl and ketamine did not differ in post-operative vomiting. PMID- 22097093 TI - Dichloromethane-methanol extract from Borassus aethiopumn mart. (Arecaceae) induces apoptosis of human colon cancer HT-29 cells. AB - Borassus aetihiopum MART (Arecaceae) is a plant used in traditional herbal medicine for the treatment of various diseases (bronchitis, laryngitis, antiseptic). In particular, their male inflorcscences were reported to exhibit cicatrizing, antiseptic and fungicidal properties. In the present study, the biological activity of E2F2, an apolar extract from Borassus aethiopum male inflorescence was investigated on colon cancer HT29 cells. Phytochemical screening was carried according to methodology for chemical analysis for vegetable drugs. Cells proliferation was determined by the MTT assay and cells cycle distribution was analysed by using laser flow cytometer (Beckman coulter). The cytoskeleton organisation was examined under a laser scanning confocal microscope (Zess). Preliminary phytochemical analysis of E2F2 extract revealed the presence of sterols, triterpenes and saponosids. E2F2 extract (1 microg and 100 microg mL(-1)) significantly inhibited cell proliferation by blocking cell population in G0/G1 phase. Flow Cytometric analysis of E2F2-treated HT29 cells showed that hypoploid cell population (sub G1 phase) increased with processing time exposures. Immunofluorescence confocal analysis revealed a disrupt actin microfilaments network in E2F2 treated-cells with a significant reduction in actin stress fibres and appearance of a random, non-oriented distribution of focal adhesion sites. These data indicate that E2F2 extract has anti proliferative and pro-apoptotic activities. Further studies are required to unravel the mechanisms of action of E2F2 extract. PMID- 22097094 TI - Expression of epidermal growth factor receptor tyrosine kinase family in fine needle aspiration and permanent specimens of invasive lobular and ductal breast cancers. AB - Recently, the role of HER-2/Neu gene amplification has been enthusiastically investigated in breast cancer. Determining the HER-2/Neu status could be achieved by evaluating either histologic samples or cytologic specimens obtained by Fine Needle Aspiration (FNA). This study aimed at determining the concordance of HER 2/Neu expression in FNA and histologic sections. FNA samples, as well as their corresponding histologic sections of 90 cases with breast cancer were evaluated in Tabriz Sina Teaching Center in a 13-month period of time. The immunohistochemistry was employed for determining the HER-2/Neu amplification for both methods. The concordance rate and agreement were determined between the two methods. Ninety specimens of women with a mean age of 50.93 +/- 10.64 (29-84) years were assessed. There were 84 cases with invasive ductal carcinoma and 6 cases with invasive lobular carcinoma. Lymph nodes were involved in 50 cases and there were vascular and neural involvement in 40 and 35 cases, respectively. Her 2/Neu was not detected in 27 cases (30%) with weak and strong amplifications in 47 (52.2%) and 16 (17.8%) cases of FNA specimens, respectively. Her-2/Neu was not detected in 29 cases (32.2%) with weak and strong amplifications in 42 (46.7%) and 19 (21.1%) cases of histologic specimens, respectively. The concordance rate was 70% between the two methods. The agree ment was statistically significant between the two methods, as well (kappa = 0.51, p < 0.001). HER-2/neu gene amplification can be reliably estimated by immunohistochemistry on breast cancer FNAs and a good correlation has been found between this and results on histological sections. PMID- 22097095 TI - Evaluation of serum levels of essential trace elements in patients with pulmonary tuberculosis before and after treatment by age and gender. AB - The purpose of this study was to evaluate the levels of Zinc, Copper, Iron and Copper/Zinc ratio in the serum of adult patients with pulmonary tuberculosis in Iran. Serum levels of Zinc and Copper were determined by flame atomic absorption spectrophotometer and scrum iron concentration was measured by using an Auto Analyzer. The study group consisted of 50 pulmonary tuberculosis patients before treatment and after 6 months of anti-tubercular therapy. Levels of scrum Zn (p < 0.001) and Fe (p < 0.001) in TB patients were significantly increased after 6 months of anti-tubercular therapy. However, serum Cu concentration (p < 0.01) and Cu/Zn ratio (p < 0.05) were decreased after 6 months of anti-tubercular therapy. Some studies indicated a strong association of Zn, Cu, Fe and the Cu/Zn ratio with TB. In this study, we found remarkable change in Cu/Zn ratio. Some researchers mentioned that serum Cu/Zn ratio could be used as an important laboratory marker for diagnosis and treatment of tuberculosis. They also mentioned that trace element levels must be closely monitored during the process of disease. PMID- 22097096 TI - Evaluation of serum C-reactive protein level and its related factors in hemodialysis patients in Sari, Iran. AB - Chronic inflammation, as reflected by increased level of acute phase protein such as C-reactive Protein (CRP) is highly prevalent in hemodialysis patients. CRP is a strong predictor of overall and cardiovascular mortality and morbidity in hemodialysis patients. This research was conducted to determine the C-reactive Protein (CRP) levels and its correlation to demographic and clinical characteristics and Laboratory values in hemodialysis patients in Sari, Iran. In a cross sectional study, 147 hemodialysis patients were studied. Patients' demographic and clinical data were recorded and also serum CRP, Cholesterol, Albumin, Phosphorous, Calcium, Hemoglobin and Hematocrit levels were measured. Overall, the mean CRP concentration was 15.8 mg L(-1). With considering to the different cutoff point (5, 6.2, 10 mg L(-1)) for CRP level, 107 patients (72.8%) had CRP level >5 mg L(-1), 99 patients (67.3%) had CRP level > 6.2 mg L(-1) and 77 patients (52.4%) had CRP level >10 nmg L(-1). The CRP levels greater than 6.2, had a direct statistically significant correlation with duration of hemodialysis and phosphorus level (p = 0.01). Also, CRP levels above 10 mg L(-1) had a direct statistically significant correlation with age and phosphorus levels (p = 0.02). According to the prevalence of high CRP level and it's correlation with age, duration ofhemodialysis and phosphorus level in hemodialysis patients, CRP level should be screened in this group of patients routinely because of its prognostic importance. PMID- 22097097 TI - Association of Pap smear abnormalities with autoimmune disorders. AB - Recently, it is hypothesized that there might be an association between immunological disorders and cervical premalignant and malignant abnormalities. Related studies have been generally focused on some particular autoimmune disease, specially the Systemic Lupus Erythematosus (SLE). This study aimed at comparing the rate of Pap smear abnormalities in female patients with autoimmune diseases and normal counterparts. In a case-control setting, 118 female patients with various autoimmune diseases (the case group) and 118 healthy female counterparts (the control group) were recruited in Tabriz Imam Reza Teaching Centre in a 24 months period of time. The two groups were matched for demographics and known risk factors of cervical malignancy. Frequencies of abnormal Pap smear testing were compared between the two groups. The autoimmune disorders were SLE (74 patients), rheumatoid arthritis or RA (32 patients), systcmic sclerosis or SS (7 patients) and ankylosing spondylitis or AS (5 patients) in the case group. Frequency of abnormal Pap smear testing was significantly higher in the case group comparing with that in the controls (7.6% vs. 1.7%; p = 0.03). Frequency of abnormal Pap smear testing was higher in the patients with SLE (8.1%) and RA (9.3%) comparing with that in the controls; However, these differences were marginally nonsignificant (p = 0.06 and p = 0.07, respectively). Frequency of cases with abnormal Pap smear testing was not statistically different between the autoimmune disorders (p = 0.99). Based on these findings and in conclusion, there might be an association between the autoimmune disorders and occurrence of premalignant or malignant lesions in cervix. Further studies with larger samples sizes are recommended. PMID- 22097098 TI - Chemopreventive activity of sesquiterpene lactones (SLs) from yacon against TPA induced Raji cells deformation. AB - Yacon is a medicinal plant used as a traditional medicine by the natives in South America. In Japan, it becomes popular as a health food. Sesquiterpene Lactones (SLs) from yacon leaves were investigated and the active SLs such as enhydrin, uvedalin and sonchifolin, bearing alpha-methylene-gamma-lactone and epoxides as the active functional groups, were identified by 1H-6000 MHz-NMR. Chemopreventive and cytotoxic activities were determined using different primary screening methods. In this study, all tested SLs strongly inhibited TPA-induced deformed of Raji cells. The IC50 values of yacon SLs from anti-deforming assay were 0.04-0.4 microM. Interestingly, yacon SLs showed more potential of chemo preventive activity than both curcumin and parthenolide. However, the cytotoxicity on Raji cells was observed at high concentration of yacon SLs. The degree of anti deformation was ranked in order: enhydrin >uvedalin >sonchifolin >parthenolide >curcumin. As according to structure-activity relationship, the high activities of enhydrin, uvedalin and sonchifolin may be due to the 2-methyl-2-butenoate and its epoxide moiety. PMID- 22097099 TI - Relaxing music for anxiety control. AB - The purpose of this investigation was to determine the characteristics of relaxing music for anxiety control. Undergraduate students (N=84) were instructed to imagine themselves in an anxiety producing situation while listening to a selection of 30 music compositions. For each composition, level of relaxation, the factors that either enhanced or detracted from its relaxing potential and the emotional labels attached were assessed. Participants were also asked to state which music components (e.g., tempo, melody) were most conducive to relaxation. Additional information was obtained through the use of a focus group of 6 undergraduate music students. This paper presents details on the characteristics of relaxing-music for anxiety control and emotional labels attached to the relaxing compositions. Furthermore, an importance value has been attached to each of the music components under scrutiny, thus providing an indication of which music components should receive greatest attention when selecting music for anxiety control. PMID- 22097100 TI - Feminist music therapy pedagogy: a survey of music therapy educators. AB - This study surveyed 188 music therapy educators regarding their views and use of feminist pedagogy and feminist music therapy. The purpose of this study was two fold: (a) to determine how many music therapy educators used feminist pedagogy and (b) to determine if there was a relationship between the use of feminist pedagogy and academic rank of the participants. Seventy-two participants responded to this study, with 69 participants included for data analysis. Stake and Hoffman's (2000) feminist pedagogy survey was adapted for this study, examining four subscales of feminist pedagogy: (a) participatory learning, (b) validation of personal experience/development of confidence, (c) political/ social activism, and (d) critical thinking/open-mindedness. The results revealed that 46% (n=32) of participants identified as feminist music therapists and 67% (n=46) of participants identified as using feminist pedagogy. Results of a mixed analysis of variance revealed a statistically significant difference within the four survey subscales (p<.0001), no significant difference (p=.32) for academic rank, and no significant interaction (p=.08) of academic rank and the four survey subscales. Tukey's post hoc analysis of the data indicated that the survey subscale measuring political activism (p<.0001) was significantly lower than the other three survey subscales. In addition, a qualitative analysis on open-ended responses is also included. Discussion of the results, limitations, and areas for future research are addressed. PMID- 22097101 TI - Clinical practice of dual-certified music therapists/child life specialists: a phenomenological study. AB - The discipline of child life enjoys a strong presence in many medical settings within the current pediatric healthcare environment. Due to the widespread establishment of child life programs, music therapists often find themselves negotiating their role and contributions to pediatric healthcare in relation to the field of child life. There is increasing interest among music therapy interns and clinicians in pursuing certification in child life to increase clinical knowledge and enhance marketability. A small, but strong, cohort of dual certified music therapists/child life specialists is currently practicing in the field, but the nuances of their clinical practice have not been systematically examined. The current study used an interpretative phenomenological approach to explore the lived experiences of eight dual-certified clinicians, and to interpret how clinicians make sense of those lived experiences. Two overarching themes of identity and flexibility arose from the analysis: issues relating to establishing, challenging, and modifying professional identity; and flexibility manifested within areas of theoretical orientation, professional role, and clinical approach. Dual-certified clinicians vary in the degree to which they integrate the fields of music therapy and child life in practice, from complete and seamless integration of the two, to exclusive practice of only one field, depending upon the bounds of their positions. Participants reported that child life training is beneficial, but not necessary for achieving advanced practice in pediatric medical music therapy. Implications for the continuing advancement of music therapy in pediatric healthcare are discussed. PMID- 22097102 TI - Steady beat and state anxiety. AB - Daily life in today's society is filled with moments of high state anxiety. State anxiety is the amount of anxiety one is experiencing in the present moment; it is not a personality trait. Many people need simple, cost-effective ways to self regulate themselves so they can sleep, be more productive, and attend to their activities of daily life. Therefore, the present study questioned whether listening to a steady beat will decrease feelings of state anxiety in healthy subjects. Participants (N=36) between the ages of 20 and 50 volunteered for the study. During this study, experimental anxiety was induced and the Visual Analog Scale served as the measurement tool for both tests. Subjects in the control group sat in silence, while subjects in the experimental group listened to a steady beat of 66 beats per minute. The results of an independent-samples t test indicated significant differences between the groups on the posttest measure, t (34)=2.41, p=.02. Subjects who listened to the steady beat reported less anxiety than subjects who sat in silence. This study suggests that steady beat alone can reduce state anxiety, thus providing a cost-effective and accessible means for self-regulation in the midst of high state anxiety. PMID- 22097103 TI - Descriptive analysis of YouTube music therapy videos. AB - The purpose of this study was to conduct a descriptive analysis of music therapy related videos on YouTube. Preliminary searches using the keywords music therapy, music therapy session, and "music therapy session" resulted in listings of 5000, 767, and 59 videos respectively. The narrowed down listing of 59 videos was divided between two investigators and reviewed in order to determine their relationship to actual music therapy practice. A total of 32 videos were determined to be depictions of music therapy sessions. These videos were analyzed using a 16-item investigator-created rubric that examined both video specific information and therapy specific information. Results of the analysis indicated that audio and visual quality was adequate, while narrative descriptions and identification information were ineffective in the majority of the videos. The top 5 videos (based on the highest number of viewings in the sample) were selected for further analysis in order to investigate demonstration of the Professional Level of Practice Competencies set forth in the American Music Therapy Association (AMTA) Professional Competencies (AMTA, 2008). Four of the five videos met basic competency criteria, with the quality of the fifth video precluding evaluation of content. Of particular interest is the fact that none of the videos included credentialing information. Results of this study suggest the need to consider ways to ensure accurate dissemination of music therapy-related information in the YouTube environment, ethical standards when posting music therapy session videos, and the possibility of creating AMTA standards for posting music therapy related video. PMID- 22097104 TI - Effects of a single-session assertiveness music therapy role playing protocol for psychiatric inpatients. AB - The purpose of this study was to implement and measure the effectiveness of a single-session assertiveness music therapy role playing protocol for psychiatric inpatients. Participants (N=133) were randomly assigned by group to one of three conditions: (a) Assertiveness Music Therapy, (b) No Music Assertiveness, or (c) Music No Assertiveness. Participants in both assertiveness conditions role played a number of different commonly occurring scenarios at an inpatient psychiatric facility and in the community. There were no significant between-group differences in posttest quality of life, locus of control, or other subscales. However, participants in both assertiveness conditions tended to have slightly higher internal locus of control and overall quality of life scores than participants in the music no assertiveness condition. Additionally, the assertiveness music therapy condition had higher attendance rates than the other conditions. A higher percentage of participants from both the assertiveness music therapy and music no assertiveness conditions indicated they thought their session was the most helpful/therapeutic group therapy session in which they had participated; this was not the case for the assertiveness no music condition. Future research is warranted to measure the effects of protocols that can help psychiatric patients generalize skills learned in treatment. PMID- 22097105 TI - Music therapy career aptitude test. AB - The purpose of the Music Therapy Career Aptitude Test (MTCAT) was to measure the affective domain of music therapy students including their self-awareness as it relates to the music therapy career, value in human development, interest in general therapy, and aptitude for being a professional music therapist. The MTCAT was administered to 113 music therapy students who are currently freshman or sophomores in an undergraduate music therapy program or in the first year of a music therapy master's equivalency program. The results of analysis indicated that the MTCAT is normally distributed and that all 20 questions are significantly correlated with the total test score of the MTCAT. The reliability of the MTCAT was considerably high (Cronbach's Coefficient Alpha=0.8). The criterion-related validity was examined by comparing the MTCAT scores of music therapy students with the scores of 43 professional music therapists. The correlation between the scores of students and professionals was found to be statistically significant. The results suggests that normal distribution, internal consistency, homogeneity of construct, item discrimination, correlation analysis, content validity, and criterion-related validity in the MTCAT may be helpful in predicting music therapy career aptitude and may aid in the career decision making process of college music therapy students. PMID- 22097106 TI - [Getting retired--a relief or a misfortune]. PMID- 22097107 TI - Effects of changes in dynamic characteristics of the middle ear on transient evoked otoacoustic emissions. AB - Transient-evoked otoacoustic emissions are transmitted through the middle ear. The purpose of this study was to investigate the effects of dynamic properties of the transmission system on the measurability of transient otoacoustic emissions. The authors analyzed the presence of transient otoacoustic emissions in 48 children with serous otitis media regarding the tympanogram, presence and type of effusion and pure tone average findings. The results obtained in this research show the predominant absence of transient otoacoustic emissions in patients with type B tympanogram (69.1%) especially if the effusion is mucoid (77.5%) with the hearing loss of 15 decibel hearing level. This research shows that disorders in dynamic characteristics of the middle ear in patients with serous otitis obstruct the transmission of acoustic energy and affect the measurability of transient otoacoustic emissions, especially if the effusion is mucoid and hearing loss of 15 decibel hearing level. PMID- 22097108 TI - [Contemporary treatment neuropathic pain]. AB - INTRODUCTION: Neuropathic pain, or pain associated with disease or injury to the peripheral or central nervous system, is a common symptom of a heterogeneous group of conditions, including diabetic neuropathy; trigeminal neuralgia, postherpetic neuralgia and spinal cord injury. Chronic neuropathic pain should not be thought of as a symptom. It should truly be thought of as a disease with a very complicated pathophysiology. PATHOPHYSIOLOGY: The mechanisms involved in neuropathic pain are complex and involve both peripheral and central pathophysiologic phenomenon. The underlying dysfunction may involve deafferentation within the peripheral nervous system (e.g. neuropathy), deafferentation within the central nervous system (e.g. post-thalamic stroke) or an imbalance between the two (e.g. phantom limb pain). CLINICAL CHARACTERISTICS: Neuropathic pain is non-nociceptive, in contrast to acute nociceptive pain, and it can be described as "burning", "electric", "tingling", and "shooting" in nature. TREATMENT: Rational polypharmacy is often necessary and actually it is almost always the rule. It would be an exception if a patient was completely satisfied with his treatment. Treatment goals should include understanding that our patients may need to be titrated and managed with more than one agent and one type of treatment. There should be the balance of safety, efficacy, and tolerability. CONCLUSION: There are many new agents and new applications of the existing agents being currently studied which will most certainly lead to even more improved ways of managing this very complicated set of disorders. PMID- 22097109 TI - [Role of surgical resection in treatment of pancreatic adenocarcinoma]. AB - INTRODUCTION: Pancreatic adenocarcinoma is the fifth leading cause of death from malignant diseases. The total five-year rate is bellow 5%, but in patients who underwent pancreatic resection, the five-year rate may be up to 20%. Surgical resection is still the only therapeutic option that offers the possibility of cure. In recent decades, the perioperative mortality rate has been significantly reduced in the institutions performing a number of these operations per year and has become less than 5%. Postoperative morbidity remains high. MATERIAL AND METHODS: The results of surgical resection in the treatment of pancreatic adenocarcinoma have been analyzed. A retrospective study included the patients operated at the Department for Abdominal, Endocrine and Transplantation surgery, Clinical Center of Vojvodina. RESULTS: In the period from February 1st 1998 to February 1st 2007 a total of 67 patients with pancreatic adenocarcinoma underwent resection. The average age of patients was 58.81 +/- 1.42 years. There were 44 (65.7%) male and 23 (34.3%) female patients. The most common locations of cancer were the head, then the body and the tail of the pancreas and they were found in 57 (85.1%) cases, 7 (10,4%) cases and 3 (4,47%) cases, respectively. The postoperative mortality appeared in 3 (4.47%) cases and postoperative morbidity in 21 (31.3%) cases. The average survival was 22.89 +/- 3.87 months, the median being 9.0 +/- 2.18 months. The five-year survival rate was 13.5%. CONCLUSION: For patients with pancreatic cancer, surgical resection still remains the only chance of cure. These procedures are performed with acceptable postoperative mortality and morbidity rate. The percentage of cured patients is still unsatisfactorily low. PMID- 22097110 TI - [Assessment of health-related quality of life in patients after acute myocardial infarction]. AB - INTRODUCTION: Acute myocardial infarction has negative influence on patient's quality of life. The objective of the paper was to assess the health-related quality of life in the patients one month and twelve months after acute myocardial infarction and to compare it with the healthy controls. MATERIAL AND METHODS: A prospective cohort study involved 160 patients aged from 30 to 79 and 240 healthy controls. The health-related quality of life was assessed with the Serbian version of these questionnaires: EuroQuol-5-Dimension and EuroQuolVAS. Angina pectoris was ranked according to the classification of Canadian Cardiovascular Society. Multivariate logistic regression analysis was used. RESULTS: The healthy controls had significantly higher average scores in EuroQuolVAS compared with the patients one month after acute myocardial infarction (74.35 +/- 9.42 vs 60.50 +/- 12.03, p<0.001), as well as twelve months afte acute myocardial infarction (74.35 +/- 9.42 vs 69.83 +/- 12.06, p<0.001). Significantly lower average ranges in EuroQuol-5-Dimension questionnaire and higher quality of life were found twelve months after acute myocardial infarction than one month after acute myocardial infarction (1.41 +/- 0.26 vs 1.53 +/- 0.26, p<0.001). The average ranges of angina pectoris were significantly lower in all the patients twelve months after acute myocardial infarction compared with the first month (0.78 +/- 0.51 vs 0.91 +/- 0.44, p<0.01). The multivariate regression analysis confirmed thrombolytic therapy, percutaneous transluminal angioplasty and age to be important factors influencing health-related quality of life. CONCLUSION: The patients assessed their health condition to be significantly higher twelve months after acute myocardial infarction than one month after it. The health-related quality of life was significantly higher in patients who had undergone the percutaneous intervention than in those who had been treated with the thrombolytic therapy. PMID- 22097111 TI - Prognostic significance of intracranial pressure monitoring and intracranial hypertension in severe brain trauma patients. AB - Since without prospective randomized studies it is not possible to have a clear attitude towards the importance of intracranial pressure monitoring, this study was aimed at examining the prognostic effect of the intracranial pressure monitoring and intracranial pressure oriented therapy in severe brain trauma patients, and at defining optimal intracranial pressure values for starting the treatment. Two groups of patients were treated in the study, one consisted of 32 patients undergoing intracranial pressure monitoring and the second group of 29 patients without intracranial pressure monitoring in the control group. The study was prospective with groups randomized. There were 53% survivals in the intracranial pressure monitored patients and 34% in the control group, with no significant difference in the survival rate between the two groups (chi2=2.11; p=0.15; p>0.05). The average intracranial pressure in the patients with intracranial hypertension who died was 27 mm Hg, while in the patients who survived the average intracranial pressure was significantly lower (Student's t test: t=2.91; p=0.008; p<0.01) and it was 18 mm Hg. We recommend starting intracranial pressure oriented therapy when the patient's intracranial pressure exceeds 18 mmHg during 2 hours of monitoring. PMID- 22097112 TI - [Influence of the first episode duration on further course of bipolar disorder]. AB - INTRODUCTION: Bipolar disorder has been continuously studied due to its high prevalence and incidence. The aim of this study was to explore the influence of duration of the first episode of bipolar disorder on the further course of this disorder. MATERIAL AND METHODS: The research was conducted as a retrospective prospective, naturalistic study, which included 65 bipolar patients admitted to the hospital. We used Student's t-test in addition to descriptive parameters, mean, median and standard deviation. We followed the 5-year course of the disorder after the first episode. RESULTS: Having examined the medical records of the first episode and five-year follow-up of the course of the disease we found a statistically significant difference (2 vs 1.54; df=120; p<0.05) in the number of episodes following the first episode between the patients whose first episode was longer than 2 months and the patients whose first episode was shorter than 2 months. In addition, we found a statistically significant difference (55.42 vs 42.3; df=120; p<0.05) in duration of episodes that followed the first episode between the patients whose first episode was longer than 2 months and the patients whose first episode was shorter than 2 months. DISCUSSION: Since these results are in accordance with the literature, we ought to point out the possibility of developing chronic syndromes in patients with longer first episodes. CONCLUSION: This study is a modest contribution to the trend of studying bipolar disorder. Better knowledge of the course would enable better treatment, prognosis and outcome of this disorder. PMID- 22097113 TI - Thromboprophylaxis implementation during pregnancy in women with recurrent foetal losses and thrombophilia. AB - Recurrent foetal loss is a significant clinical problem, occurring in 1-5% of reproductive females. Inherited or acquired thrombophilia has been diagnosed in 50-65% of women with history of unexplained foetal loss. The low molecular weight heparin was applied in 24 women with inherited thrombophilia and previous recurrent foetal loss and in 6 women with primary antiphospholipid syndrome throughout their following pregnancies. The dose of low molecular weight heparin for the majority of women was 35-75 u/kg. Women with primary antiphospholipid syndrome received both low molecular weight heparin and aspirin 50-100 mg daily. Implementation of thromboprophylaxis resulted in successful pregnancy outcome in 29 out of38 pregnancies, which represents a significant improvement of pregnancy outcome in comparison to previous 81 pregnancy losses. The number of treated pregnancies in our study is small, but the rate of successful pregnancy outcomes is high (76%), indicating that low molecular weight heparin may be a promising approach to women with thrombophilia and recurrent foetal loss. PMID- 22097114 TI - [Classical and molecular methods for diagnosis of Chlamydia trachomatis infections]. AB - INTRODUCTION: Genital Chlamydia trachomatis infection is the leading cause of bacterial sexually transmitted diseases in industrial countries, particularly among young people. The consequences of chlamydial infections may involve pelvic inflammatory disease, ectopic pregnancy and tubal factor infertility. METHODS: Available tests for detection of chlamydia in men and women include culture in tissue culture cells, direct immunofluorescence test, enzyme immune assay, nucelic acid probe hibridization and polymerase chain reaction. Nucleic acid amplification tests use different ribonucleic and deoxyribonucleic acid regions as target molecules for amplifying Chlamydia trachomatis ribonucleic/deoxyribonucleic acid in clinical samples. Nucleic acid amplification tests are more sensitive than non-nucleic acid amplification tests. CONCLUSION: Although screening programmes exist in a number of countries, the continuously increasing prevalence of chlamydial infections demonstrates the necessity for defining the best method for the diagnosis and the population for screening. PMID- 22097115 TI - [Frequency of vancomycin-resistant enterococci isolated from blood cultures from 2008 to 2010]. AB - INTRODUCTION: Enterococci are important hospital-acquired pathogens. The most commonly isolated species of the genus, Enterococcus faecalis and Enterococcus faecium are the third to fourth-most prevalent nosocomial pathogens worldwide. The aim of this study was to determine the frequency of resistance to vancomycin and other antimicrobial agents of Enterococcus spp strains isolated from blood cultures of hospitalized patients. MATERIAL AND METHODS: During the three-year period, from 2008 to 2010, 132 strains of Enterococcus spp isolated from blood cultures of hospitalized patients were tested for their susceptibility to ampicillin, vancomycin, gentamycin (high-level resistance), erythromycin, chloramphenicol, teicoplanin, ciprofloxacin by disc diffusion method according to the Clinical and Laboratory Standards Institute recommendations. Susceptibility of vancomycin resistant E. faecium to the same antibiotics and to linezolid, quinopristin/dalfopristin and tigecyclin was determined using VITEK system. RESULTS AND DISCUSSION: Resistance to vancomycin was detected in 21 (15.9%) Enterococcus spp strains. The percentage of resistance to other antimicrobial agents varied from 23. l% for chloramphenicol to 81.3% for ciproflxacin. All vancomycin resistant enterococci were identified as E. faecium and belonged to phenotype VanA. The resistance to other antibiotics was very high, except for linezolid and quinopristin/dalfopristin (4.7%). The high-level aminoglycoside resistance was 87.6% for gentamycin and 95.2% for streptomycin. All isolates were resistant to ampicillin, teicoplanin and ciprofloxacin. CONCLUSION: The detected high frequency of multidrug-resistant isolates among vancomycin resistant enterococci is of great importance and suggests the need for further monitoring of susceptibility in order to take adequate measures to prevent and control spreading of resistant strains. PMID- 22097116 TI - [Role of the chosen general practitioner in educating women on the importance of regular gynecological examinations]. AB - INTRODUCTION: Since regular screening is the best way of preventing the development of cervical cancer, the objective has been set to assess the motivation of women to have regular gynecological examinations and to estimate the role of the chosen general practitioner. MATERIAL AND METHODS: The survey was performed on the basis of the prospective study done at the Health Centre "Novi Sad" in 2009 during the systematic regular examinations carried out by general practitioners. RESULTS: It was found that 60.8% of the examined women had regular checkups; 21.5% visited their doctor once in the period of two to five years and 4.9% had undergone the examination in a period > 10 years, whereas 1.9 women had never had an examination. Other examinees had occasional check-ups with various time laps between them. DISCUSSION: The reasons for not visiting a gynecologist were fear of the examination, absence of discomforts and lack of time. However, 87.2% of the examinees visited a gynecologist after they had been advised to do so by their general practitioner. Gynecological finding was good in 87.6% of the women, 3.4% were found to have carcinoma and 8.9% had some other abnormal finding. CONCLUSION: According to the obtained results, it has been concluded that the chosen general practitioner has a very important role in motivating women to have regular gynecological examinations and in educating them on the risk factors for developing malignant diseases and on the possible prevention. PMID- 22097117 TI - Comparison of the results of treatment of humeral shaft fractures by different methods. AB - The aim of this study was to compare the functional results of non-operative and different operative techniques of managing humeral shaft fractures. The average follow-up was one year after the trauma in 61 patients with united fracture, where the initial method of treatment was the definitive one. The patients were divided into four groups: 22 were treated with hanging cast, 20 with intramedullary nails, 10 with dynamic-compressive plates and screws and 9 with external fixators. We estimated the presence of bone union by radiographic and clinical evaluation and compared the results with Constant and Mayo scores. The etiology of injuries was falls and traffic accidents in 87% of cases. The hanging cast group had the most of elbow contractures and insufficient results of functional scales. The plating group had lower average values of scores than nails, especially considering the elbow function. Among subgroups, the locked intramedullary nails had better results than Ender nails. The most complicated cases treated with Ilizarov and Mitkovic's external fixators had good results, especially in the treatment of open humeral shaft fractures; however, the rehabilitation period was longer. The best average functional results were recorded in the nailing group because of rigid fixation, solid callus formation and return to everyday activities in the shortest time. PMID- 22097118 TI - [Contemporary methods and mobile denture cleansers and theirs significance for older population]. AB - A dramatic increase in the number of people living in their seventies, eighties and nineties is associated with a loss of teeth and the use of mobile dentures. The aim of this paper was to highlight the consequences of poor denture hygiene on oral and general health in vulnerable elderly people, in long-term hospitalized elderly patients and in long-term institutionalized elderly in nursing homes. DENTURE DEPOSITS AND CONSEQUENCES OF POOR DENTURE HYGIENE: The number of bacteria living in the mouth is getting larger after putting denture on. Namely, a small "space" develops between jaw and denture, creating perfect conditions for bacterial growth. Denture becomes a "reservoir" of micro organisms. Denture deposits such as bacterial plaque, fungi, tartar and remnants could be responsible for stomatitis prothetica, cheilitis angularis, inflammatory fibrous hyperplasia, halitosis (bad breath), dental caries in mobile denture carriers, mucositis and periimplantitis in mobile implant over-dentures carriers, accelerated destruction of denture materials for underlying, such as denture base soft liners, respiratory airways diseases, bacterial endocarditis and gastrointestinal infections. REMOVAL OF DENTURE DEPOSITS: It is recommendable to combine mechanical and chemical denture cleaning. Denture submersion into a commercial cleansing solution for less than one hour is an effective cleaning method. Commercial cleanser: specifically intended for dentures with metal parts should be used for those dentures. Commercial cleansers with a new component of silicon polymer, whose thin layer surrounds all denture surfaces and disables oral bacteria to agglomerate, are effective and useful. Preventive hygienic treatments are very important in hospitals and homes for the aged, bearing in mind that old and ill persons reside here. Those institutions are recommended to get equipped with ultrasound denture cleaners. IMPORTANCE OF WRITTEN BROCHURE ON PROPER DENTURE HYGIENE: Patients should be verbally instructed and showed about cleaning techniques, but also written instructions inform of brochure should be distributed in order to achieve better effects. PMID- 22097119 TI - [Prediction of renal dysfunction in patients with obstructive icterus]. AB - INTRODUCTION: Renal dysfunction is one of complications in patients with obstructive icterus. It is important to recognize it early and take adequate measure to prevent its occurrence. One third of the patients with obstructive icterus have deterioration of renal function before surgical intervention. The aim of the research was to assess the renal dysfunction markers in patients with obstructive icterus. The following factors were examined: diuresis, urinary sodium concentration, sodium excretory fraction, urine osmolality, osmotic concentration index, creatinine concentration index and renal index of lesion. MATERIAL AND METHODS: The study included 85 patients with obstructive icterus (50 patients before surgical intervention and 35 after surgical intervention) and 30 patients without icterus as a control group. The patients with normal renal function before the development of the disease were included. RESULTS: Malignant etiology was present in 39 patients and benign in 46 patients of the examined group. The evaluation parameters (of renal function were examined in all of the patients. Creatinine concentration index led to the greatest change in the coefficient value of an internal consistency, showing that it was the best renal function marker in the examined group of patients with icterus. The next one was the urinary osmolality, since its exclusion would lead to a decrease in the value of Cronbach a coefficient to 0.06. Icterus and surgical intervention show statistically significant effects to change in the value of the markers of laboratory differentiation of renal function, observed as an entire set. DISCUSSION AND CONCLUSION: The examination showed that the concentration clearances of creatinine and urine osmolality are the parameters which point to the probability of renal dysfunction occurrence in obstructive icterus. PMID- 22097120 TI - [Non-immune hydrops fetalis--clinical experience in newborn infants]. AB - INTRODUCTION: Non-immune hydrops fetalis is a condition of excessive accumulation of extravascular fluid without identifiable circulating antibody to erythrocytes membrane antigens. In newborn infants it is characterized by skin oedema and pleural, pericardial or peritoneal effusion. In the era of routine Rh immunization for the prevention of foetal erythroblastosis, non-immune pathophysiologic mechanisms are presented in 76-87% of all hydropic newborns. Non immune hydrops fetalis can be associated with numerous and various disorders. The mortality rate may exceed 50%. This study was aimed at presenting our clinical experience in treating newborn infants with non-immune hydrops fetalis. MATERIAL AND METHODS: A retrospective-prospective study included newborn infants with non immune hydrops fetalis, who were treated in the Neonatal Intensive Care Unit of Mother and Child Health Institute of Serbia between January 1, 2001 and October 31, 2010. All valid data about aetiology, diagnosis, clinical course and outcome were recorded. RESULTS: The diagnosis of non-immune hydrops fetalis was made in 11 newborns. The etiologic diagnosis was established in 8 patients: anaemia due to fetomaternal transfusion in 4 patients and conatal cytomegalovirus infection, intracranial haemorrhage, isolated pulmonary lymphangiectasia and diffuse skin and mediastinal lymphangiomatosis in the remaining 4 patients. CONCLUSION: Non immune hydrops of newborn infant is associated with a high mortality rate and requires complex diagnostic and therapeutic procedures. An optimal management of neonates with non-immune hydrops fetalis demands a multidisciplinary approach to the treatment in a neonatal intensive care unit. PMID- 22097121 TI - ["Basics of delivery" by Dr Miladin Velickovic, the first text-book on obstetrics in our country]. AB - INTRODUCTION: In order to establish the School of Medicine in Belgrade it was necessary, among other things, to prepare textbooks for undergraduate studies in Serbian language. Considering the gynaecology and obstetrics in general, it is interesting to mention that the manuscript "Basics of delivery", which may be considered the first textbook of obstetrics in our country, was prepared to be published in 1925 by Dr. Miladin Velickovic, a Head of Gynaecology Department of the State Hospital in Novi Sad. that is, the author who had never been engaged in teaching activities. BOOK REVIEW AND DISCUSSION: This text of 502 pages and 220 pictures encompassed the teaching material in obstetrics and basics of neonatology in such a way that it fulfilled the void in this kind of literature in our milieu. Three years later, Dr. Velickovic had his book "Gynaecological haemorrhages and menstrual disorders" published, which was meant to assist medical students to study gynaecology more comprehensively. Dr. Velickovic was inspired to write this text by emotional reasons as well. Namely since he had been granted the scholarship by baroness 'Eufemija Jovic' Fund, he was sent to study medicine in Budapest. Without sufficient knowledge of Hungarian, he realized the importance of having the textbooks for medical students in their native language, and therefore, he did his best to achieve this vision. CONCLUSION: This paper includes the review of book, "Basics of delivery", which may be considered the first textbook of obstetrics in our country, as well as biographical data of Dr. Velickovic, whose personality has been gradually falling into oblivion. PMID- 22097122 TI - [Current situation and future in treatment of lumbar intervertebral disc protrusion with diskoscope]. PMID- 22097123 TI - [Minimally invasive percutanuous cannulated pedicle screw system fixation for the treatment of thoracolumbar flexion-distraction fracture without neurologic impairment]. AB - OBJECTIVE: To explore the feasibility and effect of percutanuous cannulated pedicle screw AF system fixation for the treatment of thoracolumbar flexion distraction fracture without neurologic impairment. METHODS: From June 2008 to June 2010,21 patients with thoracolumbar flexion-distraction fracture were treated with percutanuous cannulated pedicle screw fixation. There were 16 males and 5 females with the mean age of 32.7 years ranging from 23 to 55 years. Injured levels 5 cases was in T12, 13 was in L1, 3 was in L2. According to classification of AO, B1 was in 13 cases, B2 was in 8 cases. ASIA grade of all the patients were grade E. The mean operative time, bleeding volume, lengths of stay were evaluated. All the patients took the X-ray and three-dimensional CT reconstruction to observe the fracture healing and to measure the height of the anterior border of fracture vertebral body and the Cobb angle of kyphosis. The visual analogue scales (VAS) were compared preoperation and postoperation. The clinical effects were analyzed according to Oswestry Disability Index (ODI) from 10 aspects, including pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, traveling. RESULTS: All the operations were successful and the mean time was (109.0+/-16.0) min, blood loss was (90.0+/ 15.0) ml, lengths of stay was (7.7+/-2.3) d. No postoperative neurological deficits or wound infection occured. One case occurred subcutaneous fluid of incision and 1 case occurred delayed healing of incision. Fifteen patients were followed up with an average of 16.7 months (12-33 months). The VAS score improved from preoperative 8.3+/-1.7 to 1.8+/-1.2 at final follow up (P<0.05). The ODI of last follow-up was (10.0+/-1.2)%. Three-dimensional CT reconstructions and X-rays showed the height of vertebral body increased from preoperative (54.0+/-17.1)% to (82.7 - 3.5)% at 12 months after operation (P<0.05). Cobb angle of kyphosis changed from preoperative (23.0+/-13.1) to (6.9+/-5.1) degrees at 12 months after operation (P<0.05). The healing time of fracture was (4.7+/-0.3) months. There were no significant loss of vertebral height or kyphosis correction between postoperative 1 months and last follow-up (P>0.05). There were satisfactory fracture reduction and good position of internal fixation,and no loss of reduction within 12 months and no fixation failure in follow-up. CONCLUSION: The minimally invasive percutaneous cannulated pedicle screw fixation technique is feasible in treatment of thoracolumbar flexion-distraction fracture without neurologic impairment. This technique can avoid re -injury of posterior ligaments and bone structure, and may rebuild posterior tension band structure with the advantages of less trauma, less bleeding,shorter operative time, rapid postoperative recovery and so on. PMID- 22097124 TI - [Follow-up of discectomy with transforaminal endoscope through interlaminar approach for lumbar disc herniation]. AB - OBJECTIVE: To evaluate the outcomes of discectomy with transforaminal endoscope through interlaminar approach in treating lumbar disc herniation. METHODS: From April 2009 to April 2010, the clinical data of 27 patients with lumbar disc herniation were retrospectively analyzed. The patients were treated with discectomy by transforaminal endoscope through interlaminar approach, including 20 males and 7 females, with an average age of 41.8 years, ranging from 21 to 69 year; of them, 12 patients with "from inside to outside" approach and 17 patients with "from outside to inside" approach. All the patients were followed up. Clinical effect were evaluated according to Oswestry Disability Index (ODI) and modified MacNab standard. RESULTS: The operation of one case was stopped because of unobvious visual field of bleeding and the one case was transferred to microendoscopic discectomy. Other operations of 25 cases were successful. Among 27 patients, 20 cases were followed up from 12 to 24 months with an average of (18.0+/-2.5) months. The mean of ODI improved from preoperative (75.4+/-7.8)% to (13.0+/-20.5)% at final follow-up (P=0.000). According to modified MacNab standard, 7 cases obtained excellent result, 9 good, 1 fair and 3 poor. Among the poor outcome, one patient accepted the classical discectomy because of recurrent herniation of same level three months later,and the other two need take medicine. CONCLUSION: The discectomy with transforaminal endoscope through interlaminar approach for lumbar disc herniation is effective by decompress through from outside to inside access and from inside to outside access,the former is recommended to the dural sac and nerve root compressed to collateral side by huge protrusion and the latter is recommended to relatively smaller protrusion with long time conservative therapy. PMID- 22097125 TI - [Micro-endoscopic discectomy for the treatment of lumbar disc herniation in senile patients over seventy years old]. AB - OBJECTIVE: To explore applicability and therapeutic effects of Micro-endoscopic discectomy (MED) for the treatment of lumbar disc herniation in senile patients over seventy years old. METHODS: Thirty-two patients over seventy years old with lumber disc herniation were treated by MED from December 2007 to June 2010. Among them,20 patients were male and 12 patients were female,ranging in age from 70 to 86 years, with an average of 78.5 years old. The course of diseases ranged from 2 weeks to 30 years, with an average of 3.5 years. The main clinical symptoms were low back pain with radiating pain in lower extremities, especially under the keen joint. The surgical time, blood loss, complications and function recovery were evaluated retrospectively immediately after operation. X-ray at 1 week after operation was used to observe the change of physical curvature of lumbar; MRI at 1 month after operation was used to observe the radiographic change of lumbar before and after treatment; MacNab standard was applied to evaluate the therapeutic effects at 3 months after operation. RESULTS: The mean follow up period was 12.5 months (from 3 to 30 months). The mean operative time was 60 min (from 30 to 120 min) and the mean blood loss was 45 ml (from 15 to 150 ml). Leakage of cerebrospinal fluid occurred in 1 case, the operation continued after pressing by brain cotton and without nerve root and vessels injury; 1 case aggravated after revive, but other patients were eased. X-ray at 1 week after operation showed physical curvature of lumbar of 25 patients improved; MRI at 1 month after operation showed residue intervertebral disc and calcification tissue in 8 cases. Eleven patients still had numbness of limbs,but the pain and tenderness of limbs relieved. According to MacNab standard at 3 months after operation, 25 cases got an excellent result (78.1%), 6 good (18.8%) and 1 fair (3.1%). CONCLUSION: MED is effective for the senile patients over 70 years old with lumbar disc herniation and promotes ambulation earlier. MED has the advantage of minimal invasive, less blood loss and good clinical effects; MED is suitable for the patients with obvious radiating pain in lower extremities, especially under the keen joint and combine with mild spinal stenosis and root stenosis. PMID- 22097126 TI - [Treatment of lumbar disc herniation combine with buttock tender node with Pizhen]. AB - OBJECTIVE: To observe the therapeutic effects of Pizhen in treating lumbar disc herniation combined with buttock tender node. METHODS: From August 2009 to February 2010,83 patients (29 males and 54 females) with lumbar disc herniation combined with buttock tender node were randomly divided into the Pizhen group and acupuncture group. Pizhen group were treated with Pizhen manipulation, inserting needle by vertical prick with quacking inserting and quick withdrawing the needle, no rotating and the depth was through the surface of fascia, two times as a course of treatment; acupuncture group were treated with acupuncture, inserting Ashi-point, retaining the needle 20 min, ten times as a course of treatment. VAS scoring at the end of treatment and B ultrasonic image at 3d after treatment was carried out to observe the therapeutic effects. RESULTS: B ultrasonic image of buttock tender node showed inflammation reaction or ellipse. The width of the inflammation reaction decreased after treatment, but there has no statistical significance (P=0.635). There was no significant difference between two groups (P=0.813). CONCLUSION: Pizhen manipulation is better than acupuncture. B ultrasonic image gives morphological performance of buttock tender node, the content is inflammatory infiltrates. B ultrasound has certainly significance in diagnosing, treating and evaluating the clinical effect of Pizhen manipulation on treating buttock tender node. PMID- 22097127 TI - [Micro-decompression procedure for the treatment of lumbar spinal stenosis with multilevel]. AB - OBJECTIVE: To summarize the clinical application results of the micro decompression procedure for the treatment of lumbar spinal stenosis with multilevel. METHODS: From January 2004 to December 2008, 40 patients with lumbar spinal stenosis with multilevel were treated by micro-decompression procedure. There were 28 males and 12 females, ranging in ages from 55 to 80 years,with an average of 58 years. The course of this disease ranged from 18 months to 12 years,averaged 32 months. Forty patients with lumbar spinal stenosis with multilevel were diagnosed by CT or MRI examination. There were 20 cases with two levels stenosis (L4,5 and L5S1), 15 cases with three levels stenosis (L3,4, L4,5 and L5S1), and 5 cases with four levels stenosis (L2,3, L3,4, L4,5 and L5S1). The therapeutic effects were evaluated according MacNab standard in aspect of pain, bladder function, range of lumbar spine motion and muscle strength of lower limb. RESULTS: All of the incisions healed without infections and complications. The mean operation time of each side was 70 minutes (ranged from 50 to 90 minutes), and mean blood loss was 150 ml (ranged from 90 to 200 ml). All the patients were followed up from 22 to 52 months with an average of 26 months. According to MacNab standard, 28 cases got an excellent result, 10 good and 2 poor. CONCLUSION: Operative treatment for lumbar spinal stenosis with multilevel should focus on the symptom sites causing by neural compression and preventive decompression operations are not necessary for nonsymptomatic sites. The micro decompression procedure can be easily tolerated by older patients;it can decrease the damage to the posterior stabilizing structures of the lumbar spine. It is easily to access to spinal canal and decompress the nerve roots. PMID- 22097128 TI - [Clinical analysis of CT guided unilateral PVP for the treatment of osteoporotic vertebral compression fracture in senile patients]. AB - OBJECTIVE: To evaluate the therapeutic effect and security of CT guided unilateral percutaneous vertebroplasty (PVP) for the treatment of osteoporotic vertebral compression fracture (OVCF) in senile patients. METHODS: From April 2009 to June 2010, 26 patients undergoing CT guided unilateral percutaneous vertebroplasty were analyzed retrospectively. There were 9 males and 17 females,ranging in age from 60 to 85 years with an average of (67.50+/-6.76) years, ranging in course of disease from 2 to 30 days with an average of (8.92+/ 4.36) d. The affected segments involved 35 vertebras. The major clinical manifestations of OVCF were lumbar-back pain (especially when turning over or stooping down) and unable to bear. The needle was punctured into vertebral of lesions through unilateral puncture under the CT guidance; and then 3-5 ml bone cement was injected into vertebral. Antibiotic was used 3 days to prevent postoperative infections. Postoperative complications were observed after operation, such as local leakage of bone cement, penetrating spinal cord and/or segmental spinal nerve injuries and pulmonary embolism. X-ray was used to measure the height of anterior, middle and exterior of vertebral before and after treatment. A visual analog scale (VAS) scoring was applied to evaluate pain score preoperative, 48 hours postoperative and the terminal follow-up. RESULTS: Twenty six patients achieved success in punctuation without serious complications. Local leakage of bone cement occurred in 6 cases, but without clinical symptoms or signs. One patient suffered from acute intraoperative reactions to bone cement and relieved by 5 mg dexamethasone and oxygen. All patients were followed up for 6 to 12 months [averaged (8.4+/-1.6) months]. The postoperative vertebrae height was higher than preoperative,but there was no statistical difference between postoperative and preoperative (P>0.05). Preoperative VAS scores was 7.63+/-0.92, postoperative score was 3.00+/-1.09, the final follow-up score was 2.38+/-1.17; there was significant difference between preoperative and postoperative at 48 hours (P<0.05), but there was no statistical difference between final follow-up and postoperative at 48 hours (P>0.05). CONCLUSION: Unilateral PVP under CT guided can increase the vertebral strength and stabilize vertebral body,and the procedure is a safe and effective method for OVCF in elderly patients. PMID- 22097129 TI - [Treatment of the 3rd lumbar vertebrae transverse process syndrome with spatula]. AB - OBJECTIVE: To investigate the application and clinical effects of spatula for the treatment of the 3rd lumbar vertebrae transverse process syndrome. METHODS: From December 2009 to October 2010, 38 patients with the 3rd lumbar vertebrae transverse process syndrome were treated by spatula, of them, 33 patients were follow-up. Among the patients,19 cases were male and 14 cases were female,with an average age of (37.6+/-7.8) years (ranged from 28 to 58 years). The course of this diseases ranged from 10 days to 14 months with an average of (126.9+/-14.7) days. The main symptoms of the patients including unilateral lumbar pain, lateral bend waist limitation,the ache became even worse after exertion or prolonged sitting and radiated to the affected side of thigh and popliteal fossa,but the pain never exceed knee joint. The tenderness at the tip of the 3rd lumbar vertebrae was obviously and the contract muscle bundle could be touched. The X rays showed the two sides of the transverse were asymmetric. CT or MRI was used to exclude spinal stenosis,tumor,and intervertebral disk hernia. Spatula was applied for sow discord and solution accretion, and injected compound medicine (0.2% Lidocaine 3 ml, Triamcinolone acetonide 5 ml, add 0.9% physiological sailine 2 ml to 10 ml). If the symptoms did not improved after the first treatment, start the second treatment one week later, but it was not more than three times. According to the standard of JOA score, the effects before and after treatment were evaluated by low back pain, leg pain or numbness, gait, Straight Leg Raising test, sensory and movement disorder,bladder function test. RESULTS: Thirty-three patients were followed up for 2-12 months with an average of 4 months. All of the incisions were healed without complications. The clinical symptoms were improved and 22 cases were treated once, 7 cases twice and 4 cases 3 times. According to JOA evaluation criteria,the score before and after treatment was increased from (7.03+/-3.81) to (13.29+/-3.78), and 26 cases got excellent result, 5 good, 2 fair. CONCLUSION: 3rd lumbar vertebrae transverse process syndrome is one of the indications of the spatula. If the diagnose is correct, lesions position precisely located and operation performed properly, the treatment by spatula showed confirmed therapeutic effects, low complication and high safety. PMID- 22097130 TI - [Problems and solutions in minimally invasive process of posterior discectomy for lumbar disc herniation]. AB - OBJECTIVE: To analyze the problems and complications of posterior discectomy for lumbar disc herniation. METHODS: From January 2005 to June 2010, 497 patients with lumbar disc herniation were treated by posterior discectomy, which data were analyzed retrospectively. There were 395 males and 102 females,ranging in age from 20 to 78 years with an average of 43.7 years. Among them, 405 cases were in single gap, 86 cases were in double gaps and 6 cases were in three gaps. The complication of operation and solution was analyzed. RESULTS: The mean operative time was 70 min (from 45 to 210 min), and the mean hospitalization was 10 d (from 5 to 20 d). Forty-seven cases suffered operative complications. There were 16 cases of wrong location of segments (14 cases occurred in operation and 2 occurred after operation), 15 cases of less alleviation or aggravation of nerve symptoms (12 cases were poor alleviation and 3 cases were aggravation), 10 cases of urinary retention, 5 cases of cerebrospinal fluid leakage and 1 case of infection. CONCLUSION: Minimally invasive process of posterior discectomy in treating lumbar disc herniation may complicate with many problems. The operative effects can be improved and the complication can be decreased if the ability of location is improved,surgical indications is correct and the operation is exactly performed. PMID- 22097131 TI - [Effective analysis of percutaneous reduction and Kirschner pin fixation for the treatment of intraarticular fractures of the calcaneus in children]. AB - OBJECTIVE: To introduce and evaluate the clinical effects of percutaneous reduction and Kirschner pin fixation for the treatment of intraarticular fractures of the calcaneus in children. METHODS: From March 2001 to February 2009,12 patients with intraarticular calcaneal fractures were treated by percutaneous reduction and Kirschner pin fixation (13 feet). There were 8 males and 4 females,ranging in age from 3 to 14,with an average of 8.7 years. According to Essex-Lopresti classification, among 5 feet were tongue fractures and 8 feet were compressed fractures. According to Sanders classification, 9 feet were type II and 4 feet were type III. The Biihler angle and Gissane angle of the calcaneus were obtained before and after operation. All patients were evaluated according to Maryland Foot Score. RESULTS: All the patients were followed up for 16-71 months (means 35.9 months),and all the incisions were healed without complications and infection. The preoperative X-ray film showed that Bohler angle was (19.7+/-5.3) degrees, Gissane angle was (137.3+/-7.5) degrees. The postoperative X-ray film demonstrated that Bohler angle was (32.6+/-3.7) degrees, Gissane angle was (125.4+/-2.9) degrees. There was a significant difference between preoperative and postoperative (P<0.01). The average Maryland score was 96.3+/-2.4 (range, 92 to 100 points). CONCLUSION: Percutaneous reduction and Kirschner pin fixation is an effective minimally invasive way to treat intraarticular fractures of the calcaneus in children, it has many advantages such as minimal invasion, reliable fixation and satisfactory effects. PMID- 22097132 TI - [Experimental study of ectopic bone formation of engineered bone constructs under the periosteum of New-Zealand rabbits]. AB - OBJECTIVE: To study the feasibility of ectopic bone formation for engineered bone constructs with bone marrow stromal cells (BMSCs). METHODS: BMSCs were obtained from 3-month female New-Zealand rabbits with weight of 3 kg, induced to osteogenitor cell, were expanded by culture and then seeded into the porous beta tricalcium phosphate (beta-TCP) particles. Engineered bone constructs were implanted under the periostem of rabbit femur. Samples were retrieved and examed after 3 months. Blood vessels and osteoblast were examined through optical microscope. RESULTS: Twelve implanted engineered bone particles of 16 samples were fixed well under periosteum and rounded by periosteum. There were a lot of vessels and new bone in engineered bone. The structure of bone was disorder; the vessels arranged equally. Four cases found implanted bone freed outside of periosteum,lots of implanted material were absorbed,the volume of residual was less than osteogenesis, and lack of blood vessel. 80% engineered bone constructs attached to the femur under the periostem very well,osteogenesis was fine and vessels were growed into new bone. CONCLUSION: Engineered bone can obtained good ectopic bone under the periostem. PMID- 22097133 TI - [Effects of different concentrations of gubishu containing serum on the proliferation of rabbit articular chondrocytes in vitro culture]. AB - OBJECTIVE: To investigate the effects of different concentrations of Gubishu containing serum on the proliferation of rabbit articular chondrocytes cultured in vitro. METHODS: Articular chondrocytes were obtained from the cartilage of 1 month rabbit and cultured in vitro. They were randomly divided into 8 groups,blank and Gubishu groups in different concentrations (5%, 10%,15%, 20%), MTT assay method was adopted to observe the influence of Gubishu containing serum with different concentrations to the proliferation of chondrocytes after incubated 1, 3, 5, 7 and 9 days. RESULTS: The proliferation of chondrocytes was dependent on the concentration in Gubishu groups. At same time point,there was significant value between every groups, 20% concentration was greatest (P<0.05); There was significant differences between 5%, 10% and 20% concentration of the blank groups at same time point (P<0.05), and was not between 15% and 20% concentration at the 1, 3, 5 and 7 days (P>0.05), 20% concentration of the blank group was greatest. 20% concentrations of Gubishu containing serum was significantly greater than 20% concentrations of blank group at the 1, 3, 5 and 7 days (P<0.05). CONCLUSION: 20% concentrations of Gubishu containing serum can significantly increase the proliferation of chondrocytes, and bring the logarithmic growth period forward to the 3 day. PMID- 22097134 TI - [Treatment of forearm double fracture with manipulative reduction and hard paper splints]. AB - OBJECTIVE: To explore the therapeutic effects and complications of manipulative reduction and hard paper splints in treating forearm double fracture. METHODS: From November 2005 to December 2010,38 patients with forearm double fracture were treated with manipulative reduction and hard paper splints immobilization, including 26 males and 12 females, aged from 18 to 66 years (averaged 28 years). The time from injury to manipulation was 20 min to 2 d with an average of 8 hours. Before treatment, the patients manifested swelling, pain, deformity,abnormal activity of injured limbs, dysfunction of elbow and wrist extension-flexion and forearm supination-pronation; X-rays showed fractures occurred in radius and ulna. Fracture healing, flexion function of elbow and wrist, supination-pronation function of forearm were used to evaluated the therapeutic effects. RESULTS: All the patients were followed up, and the duration ranged from 3 to 8 months,with a mean of 5.7 months. According to Anderson grade criterion of forearm fractures, 33 cases were excellent and fracture healing, which loss of elbow or wrist flexion and extension ranging <10% and forearm rotation <25%; 5 cases were good and fracture healing,which loss of elbow or wrist flexion and extension ranging <20% and forearm rotation loss <50%; there was no dissatisfactory or failure cases. CONCLUSION: This method makes the fixation firmly, safely and utility, prevents the sore of pressing and necrosis, and worths further clinical applications. PMID- 22097135 TI - [T3, T4 pathologic fracture with incompletely paralysis caused by Langerhans cell histiocytosis: a case report]. PMID- 22097136 TI - [Treatment of high-pressure paint injection injuries of hand with debridement combined with vacuum sealing drainage technique]. AB - OBJECTIVE: To explore the effects of debridement combined with vacuum sealing drainage (VSD) technique in treatment of high-pressure paint injection injuries of hand. METHODS: From April 2005 to August 2010,14 patients with high-pressure paint injection injuries of hand were treated with debridement and VSD technique within 6 hours after injury. All the patients were male,ranging in age from 23 to 47 years with an average of 36.5 years. All injuries occurred left hand,thumb injured in 5 cases,index finger in 3 cases, middle finger in 2 cases and palm in 4 cases. Injured hands swelled obviously with poor blood circulation. When the wounds were covered with fresh granulation tissue without inflammatory effusion after operation of 3-4 times, the skingrafting (9 cases) or transfer flap (5 cases) were done on the wounds. RESULTS: All the patients were followed up from 8 to 16 months with an average of 12 months. All the wounds obtained good healing. Therapeutic effects were estimated according to TAM criteria, 7 cases were excellent,6 good and 1 fair. CONCLUSION: In high-pressure paint injection injuries of hands,debridement combined with VSD technique can avoid wound infection,promote the growth of granulation tissue. It is beneficial to wound healing. PMID- 22097137 TI - [Observation of CT three-dimensional reconstruction in the treatment of standard manipulation for lumbar intervertebral disc herniation]. AB - OBJECTIVE: To observe the morphological change of prominence through CT three dimensional reconstruction before and after manipulative treatment and in order to investigate biomechanical effect of manipulation in treating lumbar intervertebral disc herniation (LIDH). METHODS: From December 2009 to May 2010, 24 patients with LIDH (32 herniated discs) with the unilateral typing,which were treated with manipulation (on alternate day one time and every time about 20 min, 3 weeks as a course of treatment). There were 10 males and 14 females, ranging in age from 25 to 54 years with an average of 36.2 years, in course of disease from 2 days to 10 years with an average of 6.9 years. Protrusible 12 discs were in L4,5 and 20 discs were in L5S1. According to typing of distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), 5 cases were type I, 13 cases were type II and 6 cases were type III. After a course of treatment,the morphological changes of prominences were analyzed in the same level of CT three-dimensional reconstruction, including contour map of nerve root sheath side distance (TD), the distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), the deviated angle of prominence (AN value) and the sagittal index (SI value). RESULTS: From the contour map of TD, 19 patients (79.2% of the total) can be identified morphological changes after the treatment; from the distance between prominence and zygapophysial joint or vertebral plate (ligamentum flavum), 7 cases with type II turned into type I and 2 cases with type III turned into type II after treatment; AN value increased after treatment (P<0.05),it showed prominence occurred morphological change toward deviated direction of intervertebral foramina; there was no significant difference in SI value between before and after treatment (P>0.05). CONCLUSION: Standard manipulation can make prominence change, the prominence and nerve roots release, and mutual position improve,which can provide imaging evidence for the study in biomechanical effects. PMID- 22097138 TI - [Clinical study on the prevention of heterotopic ossification after total hip arthroplasty by Xiaozhong Zhitong]. AB - OBJECTIVE: To explore the therapeutic effects of Xiaozhong Zhitong mixture preventing heterotopic ossification (HO) after total hip arthroplasty. METHODS: From July 2006 to October 2009, 154 patients underwent total hip replacement surgery were randomly divided into sham group (group A, 50 cases), indomethacin group (group B, 55 cases) and Xiaozhong Zhitong mixture group (group C, 49 cases). Among 154 patients, 9 cases were primary osteoarthris, 34 cases osteoarthritis secondary to acetabular dysplasia, 98 cases osteoarthritis secondary to avascular necrosis of the femoral head, 2 cases rheumatoid arthritis, 5 cases femoral neck fracture, 6 cases other diseases. Modified Gibson approach was used during the operation. After operation, group A was no preventing treatment, group B was treated by indomethacin 50 mg every time, twice a day; group C was treated by Xiaozhong Zhitong mixture 50 ml every time, twice a day for 4 weeks. Eighteen months after operation was study termination point and X-ray (including the double hip anteroposterior,obturator oblique and iliac oblique film) was used to observe whether heterotopic ossification was formed (Brooker classification was used to evaluate ossification degree); Harris scoring was used to evaluate the function of hip joint,including PAHSS 80 scores and IAHSS 20 scores. RESULTS: All the patients were followed up,with the average of duration of 21.2 months. The condition of heterotopic ossification: for group A,there were 27 cases with heterotopic ossification(54%) ,and Brooker I in 8 cases, II in 9 cases, III in 8 cases and IVin 2 cases; for group B, there were 12 cases heterotopic ossification (21.82%), and Brooker I in 10 cases, II in 2 cases; for group C, there were 11 cases heterotopic ossification(22.45%), and Brooker I in 9 cases, I in 2 cases. There was significant difference among three group in heterotopic ossification by rank test (P<0.05), but no difference between group B and C (P>0.05); there were no significant difference among three groups before treatment in Harris, PAHSS and IAHSS by analysis of variance (one way ANOVA) (P>0.05), and has significant difference at 18 months after treatment (P<0.01). There were significant difference in Harris, PAHSS and IAHSS before and after treatment at 18 months (P<0.01). LSD-t was used to analyzed the scoring of Harris, PAHSS and IAHSS, there was significant difference among group A and group B and group C (P>0.05), but no difference between group B and C (P<0.01). There were gastrointestinal reaction in 5 of group A, 35 in group B and 4 in group C. CONCLUSION: The effect of Xiaozhong Zhitong mixture on the prevention of heterotopic ossification after total hip arthroplasty is similar to indomethacin, but Xiaozhong Zhitong mixture has the advantages of less side effects and easily acceptance by patients. PMID- 22097139 TI - [Thinking on conception and name of the "subluxation"]. AB - "Subluxation" is the core of pathological conception of spinal injuries treated by spinal manipulation. The conception of "Subluxation" not only includes changes of joint anatomy,but also emphasizes on joint dysfunction which is caused by changes of the anatomical position. The name of "Subluxation" in manual medicine is the same as modern medicine,but the content is obviously different. Nonetheless, it would be confused and not reflect the characteristics of manual practices. So we can consider changing the name of "Subluxation" in manual medicine into "Yatuowei". PMID- 22097140 TI - [Anterior-posterior operation with posteriorly limited fixation for the irreducible old dislocation of the inferior cervical vertebra combined with tiny joint interlocking]. AB - OBJECTIVE: To investigate the clinical outcome and application value of single stage circumferential surgery for irreducible old dislocation of the inferior cervical vertebra combined with tiny joint interlocking. METHODS: From Mar. 2004 to Aug. 2010,18 patients with old dislocation of the inferior cervical vertebra, in which 16 showed double joint interlocking and the others 2 showed single by the three dimensional CT scan. MRI showed that all patients had intervertebral disc injury including intervertebral disc rupture (9 cases), intervertebral disc herniation (2 cases) and the fracture of inferior cervical vertebra accompanying with intervertebral disc rupture (7 cases). All patients were treated with anterior-posterior operation with posteriorly limited fixation. Stability and fusion rate of injury segment were observe by X-ray and CT scan;function of spinal cord was assessed by Frankel grade criteria. RESULTS: All patients were followed up from 6 to 12 months with an average of 8.6 months. Dislocation of cervical vertebra got complete reduction and all grafts got fusion. There was no complication of internal fixation breakage, loosening ,displacement and there was no injury of blood vessel, nerve, esophagus during the operation. No function of spinal cord got worse after operation and the function improved by 1.2 grades in average in Frankel grade. CONCLUSION: Single stage circumferential surgery in treating irreducibly old dislocation of inferior cervical vertebra combined with tiny joint interlocking can complete recover the sequence of the cervical vertebra and relieve the compression of spinal cord and can obtain postoperative immediate stability for injury segment and will not aggravate the injury of the spinal cord and may create beneficial condition for functional recovery of the spinal cord. PMID- 22097141 TI - [Diagnosis and treatment of tarsometatarsal joint complex injury]. AB - OBJECTIVE: To explore the diagnosis and treatment of tarsometatarsal joint complex injury (TJC). METHODS: From January 2007 to January 2009,16 patients with tarsometatarsal joint complex injury were treated with open reduction and internal fixation. There were 12 males and 4 females, ranging in age from 21 to 45 years with an average of 34.1 years. Seven cases were left and 9 cases were right and all injuries caused by direct violence. Four cases caused by traffic accident 5 by fall from high and 7 by crush injury. Intercuneiform dislocation were in 11 cases, naviculocuneiform joint dislocation in 3 cases and cuboid fracture in 2 cases. All the cases were three column injuries. According to the situation of exploring and the stability, screw fixation was used for intertarsal joint, internal and middle column tarsometatarsal joint, the Kirschner wire fixation for external column and miniature plate fixation for comminuted fracture of metatarsal bones and compressible fracture of cuboid. The criteria of the AOFAS Foot and Ankle Surgery by the United States Association of ankle-rear foot functional scale was used to evaluate the clinical effect. RESULTS: All the patients were followed up,the duration ranged from 6 to 18 months(averaged 12.6 months). According to the score system of AOFAS,the total score was (74.6+/-10.4 ) points, including pain items of (29.3+/-5.9), the score of functional items of (32.4+/-5.6) points, and power lines of (12.9+/-2.6). All the incisions were primarily healed without infection, skin necrosis,fixture broken or loosen. Three cases received arthrodesis due to osteoarthritis. Four cases were followed up continually because they only had the radiologic osteoarthritis without pain. CONCLUSION: Anatomical reduction and stable fixation is the key point of the treatment of tarsometatarsal joint complex injury. Open reduction and internal fixation at the first stage is good for secondary arthrodesis. PMID- 22097142 TI - [The causes and preventive methods of misdiagnosis on wrist scaphoid bone fracture]. AB - OBJECTIVE: To retrospectively analysis the curative effect of wrist scaphoid bone fracture,and explore the causes and preventive methods of misdiagnosis. METHODS: From September 2007 to September 2010,16 patients with wrist scaphoid bone fractures were treated with plaster cast and cannulated screws fixation. There were 10 males and 6 females,ranging in age from 26 to 44 years with an average of 35 years. Among them, 12 cases manifested swelling pain of radial lateral wrist, tenderness at snuffbox area, wrist pain aggravated when stretching wrist joint, thumb or forefinger; 4 cases manifested no obviously symptoms and limited movement; 9 cases were early diagnosed; 5 cases were treated by plaster cast; 4 cases were treated with cannulated screws fixation; Among 7 cases with misdiagnosis, there were 4 cases without obvious symptoms and they were dealt with activating blood to dissipate swelling and pain process in preliminary stage. Four cases were treated with plaster cast and 3 cases with cannulated screws fixation. RESULTS: All the patients were followed up from 3 months to 39 months (averaged 21 months). Among 16 patients, 9 cases were early diagnosis, 7 cases were misdiagnosis and the rate of misdiagnosis was 43.8%. Seven cases with screws fixation were no wound infection. There was 1 case with occurred chronic pain and declining wrist mobility in both plaster cast and screw group, and both of them were misdiagnosed. According to curative effect rating criteria,these 2 cases were classified into moderate, other 14 cases were excellent. CONCLUSION: Wrist scaphoid bone fracture are easy to misdiagnose, so early diagnosis and treatment is particularly important. The main causes of misdiagnosis are nonspecific symptoms at early stage, combination with other injuries, lack of knowledge and ignorance of the further examination. Therefore, detailed inquiries and particular examination, multi-dimensional radiography and CT scan or MRI scan are the main measures for prevention. PMID- 22097143 TI - [Herbert screw fixation for the treatment of capitulum radius fracture: a report of 15 cases]. AB - OBJECTIVE: To observe the short-term therapeutic effects of Herbert screw fixation on type Mason II, Ill radial head fractures. METHODS: From March 2008 to July 2010,15 patients with Mason II, III radial head fractures were treated by open reduction and Herbert screw fixation including 6 males and 9 females with the mean age of 32 years (from 18 to 55). Seven cases were left and 8 cases were right. The interval from injury to hospitalization ranged from 3 to 10 hours. The clinical symptoms were swelling, pain, restricted movement in elbow. Bonycrepitus were heard on the elbow joint and X-ray film showed radial head fractures. Mayo elbow scoring system was used to evaluate recovery of elbow function. RESULTS: All the incisions primarily healed without myositis ossificans. All the patients were followed up for 6 to 15 months. According to Mayo elbow score, the result was excellent in 8 cases, good in 5 cases and fair in 2 cases. Mayo score was (86.67+/-1.26) points, which including pain (53.33+/-9.76), joint function(27.33+/-4.58), joint stability(6.00+/-2.07) elbow joint mobility was 70 degrees-130 degrees with the average of (105+/-10) degrees, forearm rotation was 1000-1300 with the average of (120+/-16) degrees. CONCLUSION: Treatment of Mason II, II radial head fractures with Herbert screw fixation has advantages of satisfactory reduction, reliable fixation,easy operating and early movement of joint. PMID- 22097144 TI - [Surgical treatment for multiple thoracolumbar fractures through posterior approach]. PMID- 22097145 TI - [Diagnosis and treatment of scapula fractures]. AB - Scapula fractures are rare and frequently occur secondary to high-energy trauma. Ninety percent of patients are often accompied with other potentially life threatening injuries. Diagnosis of scapula fractures are often overlooked for the heavy injuries during the first diagnosing. Most patients can get satisfactory outcome by conservative treatment. However,the operative intervention should be considered for the patients who have displaced or intra-articular fracture in order to accelerat fracture healing and improve functional recovery. In this paper,we reviewed the diagnosis and treatment of scapula fractures. PMID- 22097146 TI - [Application of collagen hydrogel in cartilage tissue engineering]. AB - Articular osteocartilage injury caused by trauma or bone disease is very common in clinical practices,the proportion of cartilage defects reached 40.31%. As the low self healing abilities of articular cartilage, the technology of tissue engineering becomes a new method to treat articular cartilage injuries with regenerative medicine. Scaffolds can be divided into preformed and hydrogel scaffolds according to properties. The traditional graft of pre-formed scaffold will bring the secondary injury to the cartilage around the defect, and the loose graft intergration with the defect surface is still a problem. Repairing irregular articular cartilage defects with ideal biomimic materials on the basis of avoiding secondary damage will become a main issue. The method of minimally invasive injecting, biomimics, and in situ remodeling brings hope to articular cartilage repairing. Below is a summary of the international and domestics reference data of recent years on collagen hydrogel in cartilage tissue engineering. PMID- 22097147 TI - Local injection of bevacizumab (Avastin) and angiolytic KTP laser treatment of recurrent respiratory papillomatosis of the vocal folds: a prospective study. AB - OBJECTIVES: Photoangiolytic laser treatment of recurrent respiratory papillomatosis (RRP) is effective, but does not reliably prevent recurrence. Therefore, sublesional injections of the antiangiogenic agent bevacizumab (Avastin) were given to assess the adjunctive effect on disease recurrence. Since bevacizumab is a new therapeutic modality for RRP, there were also primary safety objectives to determine whether there was a pegative impact on the voice and whether there were local or systemic complications. METHODS: A prospective open label investigation was conducted in 20 adult patients with bilateral vocal fold RRP. The patients underwent planned 532-nm pulsed KTP laser photoangiolysis of bilateral glottal disease 4 times with an approximately 6-week interval between procedures. At each planned laser procedure, the vocal fold that on initial presentation had a greater volume of disease also underwent 4 serial sublesional bevacizumab injections (7.5 to 12.5 mg in 0.3 to 0.5 mL). A sham injection with saline solution was administered to the other vocal fold as a control. Disease resolution was compared between subjects' vocal folds, and objective measures of vocal function (acoustic, aerodynamic), as well as patients' self-assessments of vocal function (Voice-Related Quality of Life survey), were obtained. RESULTS: All 20 patients completed the study, and there were no local or systemic complications. After 4 injections, 3 of the 20 patients had no discernible disease in either vocal fold. Of the remaining 17 subjects, 16 had less disease in the bevacizumab-treated vocal fold despite starting with more disease. Only 1 of the 17 had more disease in the bevacizumab-treated vocal fold after 4 injections. Moreover, 7 of the 20 patients (35%) did not require a laser procedure in the vocal fold that had received 4 bevacizumab injections, as compared with 3 of the 20 vocal folds (15%) that were treated with laser alone. All of the vocal function measures displayed statistically significant posttreatment improvements, except for average fundamental frequency in the 3 female patients, in whom it fell below the normal range. CONCLUSIONS: This prospective investigation provided evidence that bevacizumab injections enhanced KTP laser treatment of glottal papillomatosis without systemic or local complications. Coupling the antiangiogenesis agent bevacizumab with KTP laser photoangiolysis is conceptually synergistic and scientifically promising since the mechanisms of action are complementary. PMID- 22097148 TI - Validity and efficacy of a pediatric airway foreign body training course in resident education. AB - OBJECTIVES: We evaluated the validity and efficacy of a pediatric airway foreign body simulation for otolaryngology resident training. METHODS: We created a course using a high-fidelity toddler mannequin designed to instruct and evaluate otolaryngology residents in pediatric airway foreign body management. Seven junior and 5 senior residents participated. Their performance was evaluated by 2 observers using an Objective Structured Assessment of Technical Skills (OSATS) instrument. RESULTS: By the third trial, all junior and senior residents scored a proficiency level of "independent without errors" or "independent and efficient," and the performance of the junior residents was not different from that of the senior residents. After completing the course, the junior residents self-rated their abilities as commensurate with those of a senior resident, and senior residents rated themselves capable of performing foreign body extraction without supervision. All participants felt that the course and simulator had good overall realism and a realistic feel, demonstrating face validity. Perhaps most importantly, the residents' highest ratings were for "facilitated management of complications" and "facilitated working with the operating room team"--areas difficult to teach during live surgical procedures. CONCLUSIONS: This pediatric airway foreign body course using a high-fidelity simulator has face and construct validity, and results in statistically improved performance and self-evaluation of all participants. PMID- 22097149 TI - Investigation of fatigue, delayed-onset muscle soreness, and spectral-based cepstral measurements in healthy speakers after neuromuscular electrical stimulation. AB - OBJECTIVES: We observed whether 30 minutes of neuromuscular electrical stimulation applied to the necks of healthy speakers would result in significant acoustic changes and perceptions of fatigue and/or delayed-onset muscle soreness (DOMS). METHODS: Twelve participants were assigned to experimental (n=6; 3 male and 3 female) and control groups (n=6; 3 male and 3 female). Neuromuscular electrical stimulation was applied to the anterior neck in the experimental group only. All participants produced 3 trials of the vowel /a/ and the Rainbow Passage before and after completing a 30-minute phonation protocol. Recorded samples were analyzed for measures of the cepstral peak prominence, the ratio of low- to high frequency spectral energy, and their respective standard deviations. Perceptions of fatigue and DOMS were rated on visual analog scales before, 5 minutes after, and 24 hours after completion of the phonation protocol. RESULTS: Statistically significant acoustic findings reflecting reduced relative sound pressure level, increased high-frequency noise, and phonatory instability were observed in the experimental group. In addition, reports of fatigue and DOMS were also reported by some participants. CONCLUSIONS: A 30-minute dosage may be too high for some people experiencing neuromuscular electrical stimulation for the first time. PMID- 22097150 TI - HSP70 antibodies in 80 patients with "clinically certain" Meniere's disease. AB - OBJECTIVES: We tested the claim that a significant proportion of patients with Meniere's disease have antibodies to heat shock protein 70 (HSP70) antigen, which may lead to defective endolymphatic sac function and vertigo attacks. METHODS: Serum samples were taken from 80 subjects with a "certain" diagnosis of Meniere's disease (American Academy criteria plus electrocochleographic confirmation of endolymphatic hydrops with tone burst stimuli) and were tested for HSP70 antibodies with the OTOblot (hsp70) Western blot assay. The response was recorded as negative, positive, or equivocal. Samples from 80 sex- and age-matched blood donors were used as controls. RESULTS: Of 80 patients with "clinically certain" Meniere's disease, 14 were positive for HSP70 antibodies or equivocal; of 80 controls, 10 were positive or equivocal. There was no significant difference (p=0.239). There was no correlation with bilateral disease, "activity" of Meniere's disease, or stage of Meniere's disease. CONCLUSIONS: Patients with an unequivocal diagnosis of Meniere's disease do not have a significantly raised incidence of HSP70 antibodies. PMID- 22097151 TI - Computed tomography-based exploration of infundibular anatomy for maxillary sinus balloon dilation. AB - OBJECTIVES: A clinically relevant reconstruction of the ethmoid infundibulum and maxillary sinus ostium was developed to use 3-dimensional computed tomographic (CT) imaging technology and measurement software in an effort to better understand the anatomy of the maxillary sinus ostium and to optimize the maxillary sinus balloon dilation technique. METHODS: A retrospective review was performed of reconstructed high-resolution CT scans of patients from a private otolaryngology practice who underwent imaging for evaluation of sinus disease using multiplanar reconstruction software. The CT scans were retrospectively obtained from patients who presented for evaluation of chronic sinus disease and were analyzed with quantitative multiplanar reconstruction software that allowed measurements to be computed in clinically meaningful planes. RESULTS: Data were obtained from 31 sinuses on 18 CT scans. The mean anteroposterior distance from the guidewire exit to the maxillary ostium was 3.5 mm, and the mean optimal guide trajectory ("clocking") angle was 17.50 from the pure axialplane (95% confidence interval, 12.58 degrees to 22.48 degrees). The curvilinear guidewire travel distance was 6.9 mm from the guidewire exit to the ostial entry. CONCLUSIONS: This study reveals specific anatomic information that is applicable to the technique of transnasal maxillary sinus balloon catheter dilation. The data collected allow surgeons to anticipate the direction in which a guidewire must be manipulated in order to correctly enter the maxillary ostium. According to the data, a gentle anterior retraction of the uncinate process and a starting guide orientation 180 from pure lateral will best facilitate maxillary sinus ostial access. Application of the readily available software used for this study affords the opportunity to predict the location of the natural ostium within the infundibulum before operation and customize the technique to each specific patient. PMID- 22097152 TI - Effect of fibrin glue on collagen deposition after autologous fascia grafting in rabbit vocal folds. AB - OBJECTIVES: Fibrin glue (FG) is a reaction product of fibrinogen and thrombin that forms a fibrin clot responsible for tissue adhesion. However, FG and its components may interfere with wound healing by interacting with cytokines such as transforming growth factor-beta (TGF-beta). The objective of this study was to investigate the effect of FG on collagen deposition after fascia grafting in the vocal folds of rabbits. METHODS: Eighteen rabbits underwent autologous fascia grafting in both vocal folds, and the left side was fixed with FG. Each animal was painlessly sacrificed after 7, 30, or 90 days. The larynx was removed, and the vocal folds were prepared for histomorphometric analysis by picrosirius red staining to evaluate collagen deposition around the graft. RESULTS: There was a significant increase in collagen density around the grafts at 90 days in the vocal folds that were fixed with FG (p=0.0102) compared with the control vocal folds. CONCLUSIONS: Application of FG altered collagen deposition around the fascia grafts, leading to significantly increased collagen density after 90 days. Differences found in the composition of the extracellular matrix in later stages of the healing process are a result of changes that occur in the beginning of this process. Therapeutic interventions, such as the use of FG and/or its components, performed in the early stages of wound healing may interfere with the complex interactions of fibroblasts, inflammatory cells, and cytokines (especially TGF-beta), thereby modulating the healing process. PMID- 22097153 TI - Effect of altered core body temperature on glottal closing force. AB - OBJECTIVES: A basic function of the larynx is to provide sphincteric protection of the lower airway, initiated by a brain stem-mediated glottal closure reflex. Glottal closing force is defined as the measured pressure generated between the vocal folds during glottal closure. One of the factors thought to affect the glottal closure reflex is a variation in core body temperature. METHODS: Four adult male Yorkshire pigs were used in this study. The subjects were studied under control conditions (37 degreesC), hyperthermic conditions (38 degrees C to 41 degrees C), and hypothermic conditions (36 degrees C to 34 degrees C). RESULTS: We demonstrated that the glottal closing force increased significantly with an increase in core body temperature and also decreased significantly with decreased core body temperature. These results are supported by neurophysiological changes demonstrated by other studies in pups and adult dogs in response to altered core body temperatures. The mechanism for these responses is thought to reside centrally, rather than in the peripheral nervous system. CONCLUSIONS: We hope that a better understanding of these aspects of glottal closure will alter the care of many patients with postanesthesia hypothermia and many sedated inmates and will also further enhance preventive measures needed to decrease the incidence of sudden infant death syndrome in overheated or febrile infants. PMID- 22097154 TI - Evaluation of pediatric sensorineural hearing loss: a survey of pediatric otolaryngologists. AB - OBJECTIVES: We sought to determine the trends in the evaluation of pediatric patients with sensorineural hearing loss (SNHL) and to determine evaluation patterns based on respondents' demographic data. METHODS: All members of the American Society of Pediatric Otolaryngology were invited to voluntarily and anonymously complete an online survey. The survey was available from September 2009 to January 2010 and addressed demographic data and tests obtained in evaluating new pediatric patients with SNHL at different age points and with different degrees of hearing loss. RESULTS: The response rate was 22.9% (79 of 345). For all ages and all types of SNHL, the most common consultations were genetics (26% to 76%) and ophthalmology (31% to 66%) consultations. Computed tomography of the temporal bones (49% to 66%), genetic testing (25% to 68%), and electrocardiography (13% to 43%) were the most commonly performed tests. Although there was no consistent difference in practice patterns by gender or years of practice, there were differences in the use of thyroid function tests, TORCH titers, and autoimmune studies by hospital affiliation. CONCLUSIONS: Type of SNHL and age are factors in the evaluation of pediatric patients with SNHL. Additionally, evaluation patterns differ according to region and hospital affiliation. The results of this study may provide guidance for otolaryngologists in making information-based and cost-effective evaluations. PMID- 22097155 TI - Campomelic dysplasia: airway management in two patients and an update on clinical molecular correlations in the head and neck. AB - Campomelic dysplasia is a rare and historically lethal skeletal dysplasia with a variable but recognizable phenotype; it affects the long bones and is associated with a variety of head and neck anomalies. Mutations in or around the SOX9 gene have been identified as the molecular origin in most patients. We briefly present 2 children who meet the diagnostic criteria for campomelic dysplasia to illustrate the various clinical manifestations. Many patients with campomelic dysplasia have airway obstruction at multiple levels. We describe our approach to managing the airway in these patients, and review recent advances in understanding how SOX9 mutations lead to the spectrum of abnormalities seen in the head and neck. PMID- 22097156 TI - Status of propranolol for treatment of infantile hemangioma and description of a randomized clinical trial. AB - OBJECTIVES: Our primary objective was to review the current use of propranolol for treatment of infantile hemangioma (IH), specifically regarding 1) the age at initiation of therapy, 2) the method of initiation, 3) the use of other adjuvant therapy, 4) the duration of therapy and relapse rate, 5) the adverse events, and 6) the outcome. Our secondary objective was to describe a randomized, controlled, single-blinded trial comparing propranolol to prednisolone for treatment of IH. METHODS: Ovid Medline and PubMed searches were completed for the MeSH keywords "propranolol" and "hemangioma." Forty-nine English-language articles were published between June 2008 and September 2010, and 28 of these reported data from a total of 213 patients. Only 6 studies treated more than 10 patients, and these were selected for review in detail (154 patients). RESULTS: The treatment was initiated during infancy in 92.9% of patients (mean, 4.5 months). Sixty-five percent of patients were treated with 2 mg/kg per day, and 25.3% with 3 mg/kg per day. Patients were monitored overnight at initiation of treatment in 3 series (59 patients), for 4 to 6 hours as outpatients in 2 series (62 patients), and initially as inpatients but later as outpatients in 1 series (32 patients). Propranolol was used as sole therapy in about two thirds of patients (103 patients). Treatment was ongoing in 46% of patients at the time of publication. The average treatment duration in the remaining patients was 5.1 months. Rebound growth occurred in 21% of patients after a mean of 4.3 months of therapy. Adverse events occurred in 18.1% of patients and included hypotension in 6, somnolence in 6, wheezing in 4, insomnia, agitation, and/or nightmares in 6, cool hands or night sweats in 2, gastroesophageal reflux in 3, and psoriasis-like rash in 1. All authors reported a favorable outcome with propranolol, but the definition of efficacy was not standardized. CONCLUSIONS: Propranolol is an attractive alternative to other treatments for IH. Despite apparent widespread use of this medication, the data are limited, and prospective studies are lacking for this indication. The relatively high rate of adverse effects supports the need for careful monitoring of patients on this therapy. Fastidious reporting of adverse events and objective evaluation of early and late outcomes are necessary to improve our understanding of the use of propranolol for this indication. PMID- 22097157 TI - AOFAS position statement regarding the future of the AOFAS Clinical Rating Systems. PMID- 22097158 TI - Chronic Achilles tendinopathy treated with eccentric stretching program. AB - BACKGROUND: This study assessed the efficacy of a modified eccentric heel-drop program (reduced time and increased duration of stretch) in treating chronic Achilles tendinopathy. METHODS: Athletes with at least 12 weeks of symptoms diagnosed clinically as chronic Achilles tendinopathy were enrolled in the study. The only treatment recommended was a 6-week eccentric stretching regimen, with each stretch being maintained for at least 15 seconds. Athletes were followed to assess the response to treatment using a Visual Analogue Scale (VAS) for pain and a patient effectiveness rating for treatment satisfaction as well as time to return to pre-injury activity level. Followup was successful in 156 (82%) of the athletes. A total of 190 athletes were seen with chronic Achilles tendinopathy. RESULTS: Mid-substance injuries were diagnosed in 168 (88%) with the remainder 22 (12%) having distal insertional injuries. Pain as assessed by VAS reduced from mean of 7.2 at commencement of the regimen to 2.9 (p<0.01) after 6 weeks of stretching. Six months post commencement of program mean pain was 1.1. Patient satisfaction was rated at 7 or above (excellent) in 124 (80%) of the athletes. For mid-substance injuries the satisfaction rating was excellent in 86%. Overall mean time to return to pre-morbid activity was 10 weeks. CONCLUSION: A modified 6 week eccentric heel-drop training regimen as the only treatment for chronic Achilles tendinopathy resulted in a high degree of patient satisfaction, reduced pain and a successful return to pre-morbid activity levels. These results were best for mid-substance rather than insertional tendinopathy. PMID- 22097159 TI - Long-term clinical outcomes following the central incision technique for insertional Achilles tendinopathy. AB - BACKGROUND: The central incision technique, more than any other exposure, allows for optimal access to the diseased Achilles tendon as well as the Haglund's prominence and the retro calcaneal bursa. We hypothesized that the central incision technique would be an effective, well-tolerated surgical incision for the surgical treatment of insertional Achilles tendinopathy with minimal to no loss of plantarflexion strength. METHODS: Retrospective review of a single surgeon's experience with 27 patients, 29 surgical procedures utilizing this central approach. Isokinetic testing of plantarflexion strength, AOFAS Foot and Ankle Survey and AOFAS hindfoot score were administered to 22 patients at a mean followup time of 4 years. An additional telephone assessment was performed at a mean followup time of 7 years. RESULTS: Average recovery time was 5.7 (range, 2 to 16) months. There was no significant difference in plantarflexion strength between the operative and nonoperative sides. At the early (4-year) assessment, 15 patients had an AOFAS hindfoot score of 100; the average AOFAS hindfoot score was 96. The long-term assessment at a mean of 7 years; 22 patients (including the two bilateral cases) reported pain scores of 0 and they had no strength deficits. Overall, there was a 96% (22 of 23) satisfaction rate. CONCLUSION: Surgical debridement and resection for insertional Achilles tendinopathy using the central incision technique appears to be a technically optimal procedure affording 96% pain-free patients out 7 years with minimal to no loss of strength. PMID- 22097160 TI - Comparison of multi-drug injection versus placebo after hallux valgus surgery. AB - BACKGROUND: Hallux valgus surgery is followed by a significant amount of postoperative pain. Local multi-drug injection can be an option for pain control, but few clinical studies exist. METHODS: Between May 2008 and July 2009, 30 consecutive patients (60 feet) received simultaneous bilateral proximal osteotomies for the correction of hallux valgus deformities. Each patient received local infiltration of the test solution made with ropivacaine, morphine, ketorolac, and epinephrine on one foot and same amount of normal saline on the other foot. The test side and the control side were randomly selected and both the patient and the surgeon remained blinded until the end of the data collection. RESULTS: The multi-drug injection resulted in significantly less pain at 4 hours after the operation through the night of the first postoperative day. The difference in visual analogue scale (VAS) between the two sides was most significant at 8 hours after the operation, and then gradually decreased through the first and second postoperative day. Mean satisfaction VAS was significantly higher on the injection side (8.2+/-0.9) compared to the control side (6.2+/-1.9, p<0.0001). CONCLUSION: Local multi-drug injection was easy to perform and safe and effective in reducing pain and enhancing patient satisfaction after hallux valgus surgery. PMID- 22097161 TI - Interobserver reliability and intraobserver reproducibility of three radiological classification systems for intra-articular calcaneal fractures. AB - BACKGROUND: The management of intra-articular calcaneal fractures is difficult. One aspect for successful management is the use of a reliable and reproducible fracture classification system (FCS). The purpose of this study was to evaluate the interobserver reliability and intraobserver reproducibility of Letournel, Sanders, and Zwipp classification systems on CT scan and the Bohler's angle measurement on plain X-ray. Furthermore, we studied if the addition of a CT scan to the plain X-ray influenced the evaluation of fracture extension to the calcaneocuboid joint. METHODS: The CT scan and plain X-ray images of 51 intra articular calcaneal fractures were evaluated two times by three observers (two radiologists and one orthopedic surgeon) within a 5-month interval. The interobserver reliability was measured using the Fleiss kappa while the intraobserver reproducibility was measured using the Cohen's kappa. RESULTS: The mean kappa values for the interobserver reliability and intraobserver reproducibility of the Sanders classification were 0.25 and 0.39, respectively, of Zwipp classification were 0.24 and 0.16, respectively, while those of the Letournel classification were 0.50 and 0.42, respectively. For the Bohler's angle, the mean kappa values for the interobserver reliability and intraobserver reproducibility were 0.34 and 0.32, respectively. The addition of CT scan images to plain X-ray found a higher incidence of calcaneocuboid joint involvement. CONCLUSION: Clinicians should be aware of the limitation regarding the interobserver reliability and intraobserver reproducibility of the Letournel, Sanders and Zwipp classification systems for calcaneal fractures. Future studies should attempt to improve the present classification systems. PMID- 22097162 TI - Precision of foot alignment measures in Charcot arthropathy. AB - BACKGROUND: Foot deformity associated with diabetes mellitus (DM) and peripheral neuropathy (PN) contributes to joint instability, ulceration and amputation. This study reports the intrarater and inter-rater measurement precision and least significant change (LSC) of radiological measures of foot deformity in subjects with DM, PN, and foot related complications. METHODS: Cuboid height, Meary's angle, calcaneal pitch and hindfoot-forefoot angle were measured from plain-film radiographs on 15 subjects with DM, PN, and foot-related complications. A foot and ankle fellowship-trained orthopedic surgeon with 23 years of experience (Rater 1) measured radiographs twice. A foot and ankle fellowship-trained orthopedic surgeon with 2 years of experience (Rater 2) and a radiologist in residency training (Rater 3) measured radiographs once. Root mean square standard deviation and LSC were calculated to determine measurement precision and the smallest change considered biologically real, not the result of chance. RESULTS: Intrarater measurement precision was: 0.9 mm for cuboid height, 3 degrees for Meary's angle, and 2 degrees for calcaneal pitch and hindfoot-forefoot angle. Inter-rater measurement precision for rater 1 versus 2 and 1 versus 3 were: 1.7 and 1.6 mm for cuboid height, 4 degrees for Meary's angle, 2 degrees for calcaneal pitch, and 3 degrees for the hindfoot-forefoot angle. The LSC was less than or equal to: 4.7 mm for cuboid, 12 degrees for Meary's angle, 6 degrees for calcaneal pitch, and 8 degrees for hindfoot-forefoot angle. CONCLUSION: Cuboid height, calcaneal pitch, and hindfoot-forefoot angle measures can be completed with relatively good measurement precision. PMID- 22097163 TI - Deltoid ligament abnormalities in chronic lateral ankle instability. AB - BACKGROUND: Treatment of patients with repeated ankle sprains and chronic lateral ankle instability tends to focus on the lateral collateral ligaments. We reviewed records to ascertain the prevalence of abnormalities of the deltoid ligament in this population. METHODS: Retrospective review of MR images and surgical reports was performed for all patients during a 3-year period that underwent surgical treatment of chronic ankle instability at a single institution. Forty-seven ankles (46 patients) met inclusion criteria. None had medial ankle pain. RESULTS: On MRI, all patients had anterior talofibular ligament tear, plus injury to one or more additional ligaments. Ninety-one percent had injury of calcaneofibular ligament. Injury to the posterior talofibular ligament was less common (49%). Deltoid ligament injuries were seen in 72% of cases (23% superficial deltoid only, 6% deep deltoid only, 43% both superficial and deep components). Of patients with injury to the superficial deltoid, 32% had an intact deep deltoid ligament. MRI correlated well to surgical findings. CONCLUSION: Deltoid ligament injuries were common in patients with lateral ankle instability who underwent reconstruction. PMID- 22097164 TI - Biomechanical comparison of the Achillon tendon repair system and the Krackow locking loop technique. AB - BACKGROUND: The Achillon" Achilles tendon repair system combines the benefits of open repair and percutaneous repair and has excellent clinical results with minimal complications. The Krackow locking loop has been the standard suture technique for many surgeons in open Achilles repair. We determined to see how the Achillon repair compared with the Krackow locking loop in a biomechanical pull out study. METHODS: Paired lower limbs of ten human cadavers were randomly split to receive repair via Krackow locking loop or via Achillon in concordance with the manufacturer's manual. Following repair, the study groups were subjected to the same tissue processing and tensioned to failure in an Instron" 8841 device. From load-displacement curves, initial linear stiffness, load to failure, and work to failure were determined. RESULTS: The predominant mechanism of failure for the Krackow stitch was the breakage of the sutures or knots. The predominant failure mechanism of the Achillon repairs was the tearing of the suture loops through the tendon tissue. Repairs using the Krackow stitch possessed an average maximum load to failure of 128.3+/-30.3 N and a work to failure of 2199.1+/-669.7 N mm. After excluding outliers, repairs with the Achillon technique resulted in a maximum failure load of 178+/-35.4 N and a work to failure of 3999.8+/-942.7 N mm that were both significantly higher than the Krackow stitch (p<0.05). The initial stiffness of the repairs was significantly higher using the Krackow stitch (10.4+/-2.0 N/mm) compared to the Achillon technique (6.6+/-2.3 N/mm) (p<0.05). CONCLUSION: The results indicate a properly performed Achillon repair can be stronger (higher load to failure) and tougher (higher work to failure) than an open repair using the Krackow locking loop, although the Krackow repair tends to be stiffer prior to plastic deformation in this model. CLINICAL RELEVANCE: Applied correctly, the Achillon repair system offers an effective, minimally invasive alternative to traditional open repair. PMID- 22097165 TI - Results of partial matrixectomy for chronic ingrown toenail. AB - BACKGROUND: Several treatment modalities which targeted partial matrixectomies, including chemical, laser matrixectomy, and partial nail avulsion, have been used in the dermatology, podiatry, and orthopaedic literature. We report our experience with surgical matrixectomy. METHODS: We treated 224 patients with severe ingrowing toenails. Segmental wedge resection of involved margin was performed. Followup time was a minimum of 10 months. RESULTS: Statistical analysis of recurrence and disease parameters such as stage of disease, infection, involved margin, previous surgery, followup time, and age showed no significant correlation (p>0.05). Twenty-two patients (9.8%) had a recurrence. Revision surgery was performed in 16 patients (7.1%). CONCLUSION: We recommend the Winograd technique with a few modifications especially for severe Stage 2 and 3 cases. Both loupe magnification and observation of soft tissue in the postoperative period were important details. PMID- 22097166 TI - Driving brake reaction time following right ankle arthrodesis. AB - BACKGROUND: The purpose of this study was to compare the brake reaction time of patients with successful right ankle fusion to normal volunteers without an ankle fusion. METHODS: Ten patients who underwent successful right ankle arthrodesis were evaluated using a driving simulator as well as an in-shoe pedobarographic measuring system. Brake reaction time, braking force, peak pressure, contact area, and the center of force between the foot and the brake pedal were recorded. SF-12 scores were obtained from all study patients. A control group of ten age matched individuals without ankle fusion was included for comparison. RESULTS: Mean brake reaction time for the ankle fusion group (0.42+/-0.14 seconds) was significantly slower than for the control group (0.33+/-0.06 seconds) (p=0.03). The center of force was consistently isolated to the forefoot in the ankle fusion group compared to controls who distributed the center of force over both the forefoot and midfoot. There was no significant difference between the ankle fusion and control groups with respect to braking force, peak pressure, or contact area. CONCLUSION: The mean brake reaction time following successful right ankle arthrodesis was significantly slower than that of normal controls. However, the fusion group time was still below the threshold for what is defined as a safe brake reaction time by the United States Federal Highway Administration. PMID- 22097167 TI - Hallux IP arthritis after MP arthrodesis managed with interpositional arthroplasty of MP joint and IP fusion: case report. PMID- 22097168 TI - Recurrent ankle equinus deformity due to intramuscular hemangioma of the gastrocnemius: case report. PMID- 22097169 TI - Avoiding suture knot prominence with suture button along distal fibula: technical tip. PMID- 22097170 TI - Osteochondral talar allograft for large osteochondral defects: technique tip. PMID- 22097171 TI - Mobility of the first ray: review article. AB - Since its introduction by Morton in the early 20th century, first metatarsal instability has been debated as a contributing cause of many foot ailments. Given our evolutionary origins, some instability at the first ray seems inevitable. It makes sense that hypermobility could be the pathology leading to the development of various forefoot disorders. The problem is that it has been difficult to prove. Only in the last decade have there been any devices with which to quantify mobility, and each of the devices measures slightly different variables. However, each of these devices has been shown to be consistent and reliable. Excessive mobility of the first ray probably cannot be considered the only "suspect." With disorders such as hallux valgus and metatarsalgia, environment and footwear may play just as important a role as hypermobility. There are some conclusions, though, that can be safely drawn at this point. * We should define the measures of first ray mobility. One recent study has suggested the terms metatarsal elevation and metatarsal translation to describe two different aspects of the problem. * Simple clinical tools may be as useful as more cumbersome research tools for assessing first ray instability. * First ray mobility on average is increased in patients with hallux valgus. * First ray mobility is increased in some patients with transfer metatarsalgia. * Although some studies show increased elevation or mobility of the first ray in hallux rigidus, other studies do not. The burden is on the current generation of foot and ankle practitioners to resolve the debate of its predecessors. By first defining the measures of instability and then applying them to large populations, the role of hypermobility may be better defined. Then we can debate how best to "fix" the problem! PMID- 22097172 TI - FootForum: DVT and SCIP. PMID- 22097173 TI - Pantalar arthrodesis for post-traumatic arthritis and diabetic neuroarthropathy of the ankle and hindfoot. PMID- 22097174 TI - [Management of bacterial exacerbations of obstructive lung diseases]. AB - Bacterial infections are a common cause of chronic obstructive pulmonary disease exacerbations. They play a main role in exacerbation of cystic fibrosis, less frequently in COPD and occasionally in asthma. Etiology of exacerbations depends on the severity of these diseases and is known to be facilitated by bacterial colonization of the airways. The clinical presentation of bacterial exacerbations is similar and their course is influenced by prompt and proper antibiotic treatment. The principles of this treatment are discussed in the paper. PMID- 22097175 TI - [Serum and urinary homocysteine in children with steroid-dependent nephrotic syndrome]. AB - Hyperhomocysteinemia is independent risk factor of cardiovascular diseases. Similarly to nephrotic syndrome (NS) predisposes to vein thrombosis. THE AIM OF THE STUDY: To evaluate serum and urinary total homocysteine (stHcy and utHcy) levels in children with the symptoms of SN, and to determine a correlation between its concentration and some parameters of hemostasis, as well as doses and the time of prednisone therapy and serum cortisol level. MATERIAL AND METHODS: The examined group consisted of 18 children with NS, aged 7.64 +/- 5.1 years, divided on two groups: A--in time o proteinuria; B--during treatment with prednisone after regression of proteinuria. Control group (C) consisted of 20 children, aged 8.5 +/- 3.6 years. Serum and urinary tHcy levels were assayed by enzyme-linked immunosorbent assay method using the Axis-Shield set. RESULTS: Serum total Hcy concentration in groups A and B did not differ from the control group (p > 0.05). Urinary total Hcy concentration in groups A and B was significantly higher than that of control (p < 0.05). A positive correlation was observed between stHcy and serum albumin as well as cortisol levels, and between utHcy and serum AT III level. CONCLUSIONS: In children with steroid-dependent NS, subclinical disturbances in hemostasis were independent of serum tHcy concentration. There was no correlation between serum tHcy and cumulated doses, as well as time of prednisone treatment, however positive correlation was found with serum cortisone. Urinary excretion of Hcy significantly increases, in comparison to control, and correlates with serum AT III level. PMID- 22097176 TI - [Evaluation of 99mTc-DTPA scyntygraphy of the relative degree of renal dysfunction after surgical removal of kidney tumor]. AB - In nephron sparing surgery (NSS) procedures the most important is oncological outcome and also the preservation of maximum renal function. Renal scyntygraphy using 99mTc-DTPA allows for assessment of renal function and its changes after surgery because of tumor. THE AIM OF THIS STUDY: To assess the loss of kidney function operated using 99mTc-DTPA scyntygraphy, depending on the location of the tumor, type of growth, and time of warm ischemia of the operated kidney. MATERIALS AND METHODS: Renal scyntygraphy was performed in 30 patients who underwent NSS procedures for renal cortical tumors of its diameter of about 3.2 cm (range: 2.5-4.1 cm) before surgery and after surgery at an average of 3.8 months (range: 2.3-5.4 months). All patients were stratified according to time of warm ischemia (up to and above 10 mines), type of tumor growth (endo- and egzophytic) and tumor location (upper, middle and lower pole). RESULTS: The relative loss of kidney function operated depending on the type of kidney tumor growth when egzophytic and endophytic was amounted to 16% (range: 12-22%) and 29% (range: 24-46%) respectively (p < 0.01), in contrast depending on the location in the upper, middle and lower pole of the kidney 24% (range: 12-36%), 31% (range: 26-46%) and 25% (range: 15-38%), respectively (p < 0.05) Depending on the time of warm ischemia for up to and above 10 mines a relative loss of kidney function of surgery was set at 21% (range: 12-24%) and 31% (range: 29-46%), respectively (p < 0.1). CONCLUSIONS: The results of this study suggest that the loss of kidney function after NSS procedures for renal cortical tumor is the largest in the middle field of tumor endophytic growth where, during the operation the time of warm ischemia is the longest. Tumors of this type should be operating in the centers performing these procedures on a routine basis. PMID- 22097177 TI - [The influence of lipoic acid on total protein concentration in the liver and spleen tissue in rats during lipopolysaccharide-induced oxidative stress]. AB - THE AIM OF THE STUDY: To evaluate the influence of lipoic acid on total protein concentration in the liver and spleen in rats during endotoxemia. MATERIAL AND METHODS: Experiments were performed on Wistar rats divided into following groups: Group I (control) received saline; Group II (LA) received lipoic acid (60 mg/kg b.w.); Group III (LPS) received lipopolysaccharide (30 mg/kg b.w.); Group IV (LPS+LA) received LPS (30 mg/kg b.w.) and 30 min later LA (60 mg/kg b.w.). Five hours after last injection rats were sacrificed, and the liver and spleen were harvested for subsequent total protein assay. RESULTS: Lipoic acid administration led to a significant increase in total protein concentration in the liver and spleen tissue of endotoxemic rats when compared to control. CONCLUSION: Lipoic acid administration during early phase of LPS-induced oxidative stress increase protein level in the liver and spleen tissue, which indicate an increase of antioxidant properties of an organism. PMID- 22097178 TI - [Prevalence of non-adherence to medication among patients treated for selected chronic conditions]. AB - The aim of this study was to assess the prevalence of this phenomenon among patients being treated for selected chronic conditions. MATERIAL AND METHODS: As many as 63,221 patients treated for hypertension, gastroesophageal reflux disease, Alzheimer disease, depression, schizophrenia, and memory loss were enrolled to this multicenter, questionnaire-based open study The primary outcome measure was patient adherence assessed with 4-item Morisky questionnaire. Only those respondents who gave negative answers to all questionnaire questions were assumed adherent. RESULTS: Out of respondents, 83.8%--in different ways--were nonadherent, and only 16.2% were adherent. Significant differences in adherence were observed with different diseases (p < 0.05), asymptomatic versus symptomatic nature of disease (asymptomatic diseases--81.5%, versus symptomatic diseases- 84.7%, in average, p < 0.05), as well as psychiatric, versus organic disease type (nonadherence in 85.6, and 82.1% patients, p < 0.05). CONCLUSION: Study proved very high prevalence of non-adherence in patient treated for chronic conditions. Patients are non-adherent particularly often in a case of psychiatric conditions. PMID- 22097179 TI - [Brugada syndrome--case report]. AB - Brugada syndrome (BS) is a rare genetically-based condition occurring usually in the third and fourth decade of human life, mainly developing in men (85%). It is manifested through permanent or periodic malignant ventricular arrhythmia leading to fainting, and consequently sudden cardiac death. Despite possessing great knowledge of the condition, implementation of cardioverter-defibrillator still remains the only effective way of treating malignant arrhythmia and of preventing sudden cardiac death. The following paper presents a case of a healthy nineteen year-old man who was admitted to the Outpatient Cardiologic Center for a sport qualifying check-up. During examination, the ECG showed some features of Brugada syndrome and the patient was sent for further hospital diagnostics. During the aimaline provocative test the ECG revealed ST elevation up to 4mm in V1-V2 leads, whereas the electrophysiological examination with standard protocol and with right ventricular apex and right ventricular output aggressive protocol did not provoke any ventricular arrhythmia. The patient was qualified for preventive treatment with recommendation for regular check-up in an outpatient cardiologic center and with a total ban on extreme sport exercises. PMID- 22097180 TI - [Takotsubo cardiomyopathy as a consequence of gastrointestinal disorder--a case preceded by exacerbation of gastroesophageal reflux disease]. AB - The etiology of takotsubo cardiomyopathy (TC), defined as a transient left ventricular dysfunction in the absence of significant coronary artery stenoses, still reminds unclear. Its onset is often associated with emotional stress or progression in the course of various disorders (including gastrointestinal ones), miscellaneous diagnostic and therapeutic procedures. We describe a case of a 67 year-old man, in whom severe left ventricular function impairment, completely reversible after a week, was observed during hospitalization for gastroesophageal reflux disease (GERD) exacerbation. The authors review the literature on TC cases which were preceded by digestive system illness, examination or surgery and discuss the possible mechanisms of this relationship. PMID- 22097181 TI - [Ascites as the first manifestation of ovarian cancer in the disseminated stage- case report]. AB - The presence of ascites is usually associated with portal hypertension, usually due to cirrhosis of the liver, with portal vein thrombosis, congestive cardiac failure, nephrotic syndrome, pancreatitis, tuberculosis. Approximately 10% of all cases of ascites occurs in malignant tumors, mostly of ovarian cancer. The purpose of this publication is to present the case of 63-year-old woman who has a basic and initial sole manifestation of disease--cancer of the ovary--was increasing ascites. PMID- 22097182 TI - [Chronic constipation in children--typical and atypical diagnosis--case reports]. AB - Constipation in children is a common health problem. It accounts for 3% of visit to general pediatrics clinics and 30% of visits to pediatric gastroenterologist. Fun(TK)ional constipation is the most common causa of contipation in children. We present three cases with chronic contstipation. PMID- 22097183 TI - [Spuriously healthy plant fats]. AB - Since long plant fats are considered by nutritionists, dieticians and doctors, as main source of essential unsaturated fatty acids) n-6 and n-3 in human diet. On the market there is plenty of oils that can be consumed directly or used to frying. Last four decades consumption of oils increased several times due to stimulated by advertisement popularization of their pro-health activity. Plant oils supply mostly multi unsaturated fatty acids n-6 excess of which disadvantageously influence human health. Determinations of changes of oxidative stability of plant fats (during processing and storage) proved that consumption of oxidation products of fatty acids and sterols may be a reason of various diseases. Both epidemiologic and clinic studies indicated that if plant fats (both oils except this from olives and margarines) have possessed pro-health properties, their several times increased consumption would liquidate the problem of arteriosclerosis and its clinical complications (heart attack, stroke). For the present, every second death in the industrial countries results from the cardiovascular disease. Morbidity of cancer is also increasing and of neurological and neurodegenerative diseases is growing up vigorously. PMID- 22097184 TI - [Osteoprotegerin--a new atherosclerosis marker]. AB - Studies on bones metabolism regulation mechanisms leaded to discovery of RANKL/OPG/RANK signal system (receptor activator of nuclear factor kappaB ligand/osteoprotegerin/receptor activator of nuclear factor kappaB). It was found that beyond bone metabolism regulation Osteoprotegerin (OPG) is involved in some other processes: apoptosis, regulation of immunological system. Data from numerous studies performed in the last years indicate potential association between OPG and cardiovascular pathology. OPG was identified as atherosclerosis marker. Molecular mechanism by which OPG exerts its atherogenic effect is not fully elucidated. PMID- 22097185 TI - [Sentinel lymph node biopsy as a new approach to colorectal cancer treatment]. AB - Some concepts considering sentinel lymph node excision in colon and rectal carcinoma are presented in the paper. Arguments pro and contra were exposed and interpret separately. The problem is still open. Current knowledge indicates that lymphatic system in colon and rectum can be very different in many patients. There is no evidence that sentinel node biopsy in this group can be useful. In patients with advanced colorectal carcinoma (T3, T4 according to TNM classification) sentinel node biopsy cannot replace regional lymph node dissection. Sentinel lymph node biopsy and localization of metastases allows to change the qualification of the NO patients to N1 (upstaging). This means the change of cancer staging in these patients and qualification to chemotherapy. In conclusion we underline that there is still too little knowledge to implement these procedures in clinical practice, that problem needs more consideration. PMID- 22097186 TI - [The main directions of research on the causes conditioning the occurrence of the borderline personality disorders]. AB - Currently, there are two main directions of explaining the occurrence of the borderline personality disorders (BPD). The first of them attempts to explain them upon the constitutional basis, finding the causes in the genetic conditioning, biological and organic factors. The other one underline a role of the psychological developmental categories. A significant role is ascribed to traumatic childhood mental experiences such as: harassment and sexual abuse, as well as neglect of emotional and developmental needs of a child. About 40-71% of the infirm with the borderline personality admits to have been sexually abused. It was observed that there is a connection between the extent of sexual abuse of an individual in childhood and the intensification of the disorders proper for the borderline personality. One should, however, point out that sexual abuse, although they are regarded as a risk factor, are not seen as specific to the infirm with the borderline personality disorders. Moreover, there is a third direction referred to in the literature, seeking the causes of the occurrence of the borderline personality in a significant influence of social-cultural and environment factors. It was noticed that there is a significant correlation between the social situation and the degree of dissemination of those disorders. The borderline personality disorders are more frequent among the people of the low social status background and with relatively low level of education. More and more frequently, theorists and clinical personnel adhere to the view that the development of that disorder is caused by a combination of neurobiological and social factors, together with the pathological qualities of early-childhood development. PMID- 22097187 TI - [Depressive disorder, treatment and sexual dysfunction--part II]. AB - Depressive disorders and antidepressant therapy have been associated with sexual dysfunction. Sexual dysfunctions are recognized as a potential side effect of antidepressant therapy. Not reliable algorithms have been developed in the presence of sexual dysfunctions in the course of depressive disorders. The most commonly used methods of treatment of sexual dysfunction in depressive disorders include: waiting for spontaneous remission, reduction in dose of a repressive drug, the change of drug discontinuation for a short time, the use of the drug after having sexual intercourse, drug holidays and corrective medications (yohimbine, phosphodiesterase type 5 and anesthetic creams). Among the most effective agents used in the treatment sre: bupropion, trazodone, nefazodone, agomelatine, tianeptine and flibanserin. Optimal antidepressant treatment should result in remission of the symptoms of the underlying illness and minimize the potential for short-term and long-term adverse effects, including sexual dysfunction. Physicians should monitor their patients for antidepressant-induced sexual adverse effects, as these may affect compliance with therapy and ultimate treatment success. PMID- 22097189 TI - [TU You-you won Lasker Debakey clinical medical research award--for her outstanding achievements in studies on artemisinin]. PMID- 22097190 TI - [Exploration on some problems in clinical study and application of disease syndrome combination model]. PMID- 22097188 TI - Personal and ambient exposures to air toxics in Camden, New Jersey. AB - Personal exposures and ambient concentrations of air toxics were characterized in a pollution "hot spot" and an urban reference site, both in Camden, New Jersey. The hot spot was the city's Waterfront South neighborhood; the reference site was a neighborhood, about 1 km to the east, around the intersection of Copewood and Davis streets. Using personal exposure measurements, residential ambient air measurements, statistical analyses, and exposure modeling, we examined the impact of local industrial and mobile pollution sources, particularly diesel trucks, on personal exposures and ambient concentrations in the two neighborhoods. Presented in the report are details of our study design, sample and data collection methods, data- and model-analysis approaches, and results and key findings of the study. In summary, 107 participants were recruited from nonsmoking households, including 54 from Waterfront South and 53 from the Copewood-Davis area. Personal air samples were collected for 24 hr and measured for 32 target compounds--11 volatile organic compounds (VOCs*), four aldehydes, 16 polycyclic aromatic hydrocarbons (PAHs), and particulate matter (PM) with an aerodynamic diameter < or = 2.5 microm (PM2.5). Simultaneously with the personal monitoring, ambient concentrations of the target compounds were measured at two fixed monitoring sites, one each in the Waterfront South and Copewood-Davis neighborhoods. To understand the potential impact of local sources of air toxics on personal exposures caused by temporal (weekdays versus weekend days) and seasonal (summer versus winter) variations in source intensities of the air toxics, four measurements were made of each subject, two in summer and two in winter. Within each season, one measurement was made on a weekday and the other on a weekend day. A baseline questionnaire and a time diary with an activity questionnaire were administered to each participant in order to obtain information that could be used to understand personal exposure to specific air toxics measured during each sampling period. Given the number of emission sources of air toxics in Waterfront South, a spatial variation study consisting of three saturation sampling campaigns was conducted to characterize the spatial distribution of VOCs and aldehydes in the two neighborhoods. Passive samplers were used to collect VOC and aldehyde samples for 24- and 48-hr sampling periods simultaneously at 22 and 16 grid-based sampling sites in Waterfront South and Copewood-Davis, respectively. Results showed that measured ambient concentrations of some target pollutants (mean +/- standard deviation [SD]), such as PM2.5 (31.3 +/- 12.5 microg/m3), toluene (4.24 +/- 5.23 microg/m3), and benzo[a]pyrene (0.36 +/- 0.45 ng/m3), were significantly higher (P < 0.05) in Waterfront South than in Copewood Davis, where the concentrations of PM2.5, toluene, and benzo[a]pyrene were 25.3 +/- 11.9 microg/m3, 2.46 +/- 3.19 microg/m3, and 0.21 +/- 0.26 ng/m3, respectively. High concentrations of specific air toxics, such as 60 microg/m3 for toluene and 159 microg/m3 for methyl tert-butyl ether (MTBE), were also found in areas close to local stationary sources in Waterfront South during the saturation-sampling campaigns. Greater spatial variation in benzene, toluene, ethylbenzene, and xylenes (known collectively as BTEX) as well as of MTBE was observed in Waterfront South than in Copewood-Davis during days with low wind speed. These observations indicated the significant impact of local emission sources of these pollutants and possibly of other pollutants emitted by individual source types on air pollution in Waterfront South. (Waterfront South is a known hot spot for these pollutants.) There were no significant differences between Waterfront South and Copewood-Davis in mean concentrations of benzene or MTBE, although some stationary sources of the two compounds have been reported in Waterfront South. Further, a good correlation (R > 0.6) was found between benzene and MTBE in both locations. These results suggest that automobile exhausts were the main contributors to benzene and MTBE air pollution in both neighborhoods. Formaldehyde and acetaldehyde concentrations were found to be high in both neighborhoods. Mean (+/- SD) concentrations of formaldehyde were 20.2 +/- 19.5 microg/m3 in Waterfront South and 24.8 +/- 20.8 microg/m3 in Copewood-Davis. A similar trend was observed for the two compounds during the saturation-sampling campaigns. The results indicate that mobile sources (i.e., diesel trucks) had a large impact on formaldehyde and acetaldehyde concentrations in both neighborhoods and that both are aldehyde hot spots. The study also showed that PM2.5, aldehydes, BTEX, and MTBE concentrations in both Waterfront South and Copewood-Davis were higher than ambient background concentrations in New Jersey and than national average concentrations, indicating that both neighborhoods are in fact hot spots for these pollutants. Higher concentrations were observed on weekdays than on weekend days for several compounds, including toluene, ethylbenzene, and xylenes (known collectively as TEX) as well as PAHs and PM2.5. These observations showed the impact on ambient air pollution of higher traffic volumes and more active industrial and commercial operations in the study areas on weekdays. Seasonal variations differed by species. Concentrations of TEX, for example, were found to be higher in winter than in summer in both locations, possibly because of higher emission rates from automobiles and reduced photochemical reactivity in winter. In contrast, concentrations of MTBE were found to be significantly higher in summer than in winter in both locations, possibly because of higher evaporation rates from gasoline in summer. Similarly, concentrations of heavier PAHs, such as benzo[a]pyrene, were found to be higher in winter in both locations, possibly because of higher emission rates from mobile sources, the use of home heating, and the reduced photochemical reactivity of benzo[a]pyrene in winter. In contrast, concentrations of lighter PAHs were found to be higher in summer in both locations, possibly because of volatilization of these compounds from various surfaces in summer. In addition, higher concentrations of formaldehyde were observed in summer than in winter, possibly because of significant contributions from photochemical reactions to formaldehyde air pollution in summer. Personal concentrations of toluene (25.4 +/ 13.5 microg/m3) and acrolein (1.78 +/- 3.7 microg/m3) in Waterfront South were found to be higher than those in the Copewood-Davis neighborhood (13.1 +/- 15.3 microg/m3 for toluene and 1.27 +/- 2.36 microg/m3 for acrolein). However, personal concentrations for most of the other compounds measured in Waterfront South were found to be similar to or lower than those than in Copewood-Davis. (For example, mean +/- SD concentrations were 4.58 +/- 17.3 microg/m3 for benzene, 4.06 +/- 5.32 microg/m3 for MTBE, 16.8 +/- 15.5 microg/m3 for formaldehyde, and 0.40 +/- 0.94 ng/m3 for benzo[a]pyrene in Waterfront South and 9.19 +/- 34.0 microg/m3 for benzene, 6.22 +/- 19.0 microg/m3 for MTBE, 16.0 +/- 16.7 microg/m3 for formaldehyde, and 0.42 +/- 1.08 ng/m3 for benzo[a]pyrene in Copewood-Davis.) This was probably because many of the target compounds had both outdoor and indoor sources. The higher personal concentrations of these compounds in Copewood-Davis might have resulted in part from higher exposure to environmental tobacco smoke (ETS) of subjects from Copewood-Davis. The Spearman correlation coefficient (R) was found to be high for pollutants with significant outdoor sources. The R's for MTBE and carbon tetrachloride, for example, were > 0.65 in both Waterfront South and Copewood-Davis. The R's were moderate or low (0.3-0.6) for compounds with both outdoor and indoor sources, such as BTEX and formaldehyde. A weaker association (R < 0.5) was found for compounds with significant indoor sources, such as BTEX, formaldehyde, PAHs, and PM2.5. The correlations between personal and ambient concentrations of MTBE and BTEX were found to be stronger in Waterfront South than in Copewood-Davis, reflecting the significant impact of local air pollution sources on personal exposure to these pollutants in Waterfront South. Emission-based ambient concentrations of benzene, toluene, and formaldehyde and contributions of ambient exposure to personal concentrations of these three compounds were modeled using atmospheric dispersion modeling and Individual Based Exposure Modeling (IBEM) software, respectively, which were coupled for analysis in the Modeling Environment for Total Risk (MENTOR) system. The compounds were associated with the three types of dominant sources in the two neighborhoods: industrial sources (toluene), exhaust from gasoline-powered motor vehicles (benzene), and exhaust from diesel-powered motor vehicles (formaldehyde). Subsequently, both the calculated and measured ambient concentrations of each of the three compounds were separately combined with the time diaries and activity questionnaires completed by the subjects as inputs to IBEM-MENTOR for estimating personal exposures from ambient sources. Modeled ambient concentrations of benzene and toluene were generally in agreement with the measured ambient concentrations within a factor of two, but the values were underestimated at the high-end percentiles. The major local (neighborhood) contributors to ambient benzene concentrations were from mobile sources in the study areas; both mobile and stationary (point and area) sources contributed to the ambient toluene concentrations. This finding can be used as guidance for developing better emission inventories to characterize, through modeling, the ambient concentrations of air toxics in the study areas. (ABSTRACT TRUNCATED) PMID- 22097191 TI - [Disease-syndrome combination clinical study on psychosomatic diseases: Yang and Yin syndrome typing for psychosomatic diseases]. PMID- 22097192 TI - [Primary study on disease-syndrome combination and clinical therapy for chronic heart failure]. PMID- 22097193 TI - [Thoughts on the cut-in point of disease-syndrome combination in the clinical study of Chinese medicinal pediatrics]. PMID- 22097194 TI - [Analysis of treating diabetes mellitus by disease-syndrome combination]. PMID- 22097195 TI - [Effect of Chinese medicine comprehensive regimen as the maintenance therapy on time to progression and quality of life of patients with advanced non-small-cell lung cancer]. AB - OBJECTIVE: To observe the effect of Chinese medicine (CM) comprehensive regimen as the maintenance therapy (MT) on time to progression (TTP) and quality of life (QOL) of patients with advanced non-small-cell lung cancer (NSCLC). METHODS: The study was a prospective, randomized and controlled clinical trial. Fifty non progressive patients with advanced NSCLC who responded to first-line therapy were randomized into the test group (25 cases, treated with CM comprehensive regimen: intravenous dripping of Chinese herbal preparation, oral administration of Chinese herbal decoction, and point application) and the control group [25 cases, treated with one of three single-agent maintenance chemotherapy regimens: pemetrexed (500 mg/m2, day 1), docetaxel (75 mg/m2, day 1), and gemcitabine (1000 mg/mi, day 1 and day 8) in the ratio of 1:1]. Each cycle consisted of 21 days. Cycles were repeated until the disease progressed, or intolerable toxic or adverse reaction occurred, or patients refused to continue the treatment. The primary end point was TTP and the secondary end point was QOL. QOL was evaluated using the European Organization for Research and Treatment of Cancer quality-of life questionnaire QLQ-LC43 (EORTC QLQ-LC43). TTP of fifty patients and QOL of 43 patients had been statistically analyzed. RESULTS: (1) The TTP in the test group was prolonged for 23 days when compared with that of the control group, with insignificant difference (87 days vs 64 days, P=0.063). (2) The scores of domains in EORTC QLQ-LC43 were statistically significantly better in the test group than in the control group (P<0.05) except cognitive and social functions, the symptoms of dysphagia and pain in other parts. CONCLUSIONS: (1) The CM comprehensive regimen as MT had equivalent efficacy on TTP when compared with single-agent maintenance chemotherapy regimen. It was advantageous over improving the QOL. (2) It is necessary to enlarge the sample size to further confirm the therapeutic efficacy of CM comprehensive regimen as MT in treatment of patients with advanced NSCLC. PMID- 22097196 TI - [Effects of modified bazhen decoction in assistant with enteral nutrition on the growth hormone, the nutritional state, and the immune function in patients with gastric cancer after operation]. AB - OBJECTIVE: To observe the effects of modified Bazhen Decoction (BZD) in assistant with enteral nutrition (EN) on the growth hormone, the nutritional state, and the immune function in patients with gastric cancer after operation. METHODS: The prospective, random, single-blinded, controlled clinical trial was adopted. 88 patients receiving gastric cancer operation were randomly assigned to the parenteral nutrition group (Group A, 27 cases), the EN group (Group B, 30 cases), and the comprehensive group (Group C, BZD in assistant with EN, 31 cases). Isocaloric and isonitrogenous parenteral nutritional support was given to patients in Group A from the operation day to the ninth day. Isocaloric and isonitrogenous EN was given to patients in Group B and C from the second day of operation till the ninth day. 100 mL BZD was nasal fed to patients in Group C during the second day to the ninth day after operation. The levels of the growth hormone, immune indices such as IgA, IgG, CD4+, CD8+, and CD4+/CD8+, etc., and nutritional indices such as serum albumin, prealbumin, transferrin, etc. were detected in the three groups one day before operation, on the 1st day after operation, and on the tenth day after operation. RESULTS: The levels of IgA, IgG, CD4+, and CD4+/CD8+, serum albumin, prealbumin, transferrin decreased more than before operation in the three groups, with statistical difference (P<0.05). On the tenth day after operation, all indices in Group B and C were somewhat improved, showing statistical difference when compared with those in Group A (P<0.05). Besides, the aforesaid indices were higher in Group C than in Group B (P<0.05). CONCLUSIONS: Modified BZD in assistant with EN could further promote the elevation of the growth hormone levels. Besides, it could further improve the nutrition state and the immune function. PMID- 22097197 TI - [Clinical study of safflower injection in treating and preventing the vascular crisis after free flap transplantation]. AB - OBJECTIVE: To observe the clinical efficacy of Safflower Injection (Al) in treating and preventing the vascular crisis after free flap transplantation. METHODS: Sixty patients undergoing free flap transplantation were randomly assigned to the treatment group and control group according to the visiting sequence, thirty in each. Free flap transplantation was performed on all patients, and medication was given 0. 5 h before flap vascular anastomosis, 1-7 days after surgery. Twenty mL Al was intravenously dripped to patients in the treatment group after adding in 250 mL 5% glucose injection, while Dextran-40 was intravenously dripped to patients in the control group. The medication was conducted once per day. The hemorheology and four indices of blood coagulation [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB)] were compared between the two groups before operation (TO), during operation (T1), 24 h after operation (T2), three days after operation (T3), and seven days after operation (T4). Meanwhile, flaps were observed and adverse reaction recorded. The clinical efficacy and safety were compared. RESULTS: Better result was obtained in the treatment group when compared their clinical efficacy (86. 67% vs 60. 00%, P<0.05). The whole blood high and low viscosity, plasma viscosity, red blood cell (RBC) volume, RBC aggregation index all decreased, and RBC deformed index increased in the two groups at T4, showing statistical difference when compared with those at T3 (P<0.05, P<0.01). There was no statistical significance in the four indices of blood coagulation when compared with any time point in the same group (P>0.05). There was no statistical significance in hemorheology and the four indices of blood coagulation between the two groups at the same time point (P>0.05). The adverse reaction rate in the treatment group was lower than that in the control group, showing statistical difference (13.33% vs 30.00%, P<0.05). CONCLUSIONS: AI could effectively prevent and treat the vascular crisis after free flap transplantation. It had less adverse reaction and good safety. It was better than Dextran-40. It was a safe and effective drug to prevent the vascular crisis. PMID- 22097198 TI - [Myocardial protection of cardioplegic solution with Salvia miltiorrhizae in extracorporeal circulation of coronary artery bypass graft]. AB - OBJECTIVE: To observe the myocardial protection of cardioplegic solution with Salvia miltiorrhizae (SM) in extracorporeal circulation of coronary artery bypass graft (CABG) and to investigate the mechanisms of SM. METHODS: 30 patients who received CABG under extracorporeal circulation were randomly assigned to two groups, the observation group (15 cases) and the control group (15 cases). Patients in the observation group received the cardioplegic solution with SM and those in the control group received the cardioplegic solution without SM. The indices such as serum SOD activities, MDA contents, LDH, CK-MB, cTnl levels, the rate of heart reskip, activated coagulation time (ACT), the time of assisted respiration, and the days of in-hospital after operation were observed in the two groups pre-operation, post-operation, 6 h and 24 h post-operation, respectively. RESULTS: When compared with the control group, MDA contents, LDH, CK-MB, cTnl levels were lower, SOD activities (all P<0.05) and heart re-skip rate (P>0.05) higher in the observation group. There was no statistical significance in the time of assisted respiration, the days of in-hospital, or ACT in the two groups (P>0.05). CONCLUSIONS: The application of cardioplegic solution with SM in extracorporeal circulation of CABG showed obvious myocardial protection. It had better effects than the cardioplegic solution with no SM. PMID- 22097199 TI - [Study on the distribution and characteristics of Chinese medicine syndrome in patients with nonalcoholic fatty liver disease]. AB - OBJECTIVE: To supply evidence for establishing the standard for Chinese medicine (CM) syndrome differentiation by investigating the distribution and characteristics of CM syndromes in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: 928 NAFLD patients' symptoms, signs, tongue and pulse parameters were studied by clinical epidemiologic survey. And the results were analyzed by the cluster analysis and factor analysis. RESULTS: The results of cluster analysis showed that the CM syndrome typings of fatty liver patients were mainly classified as dampness heat accumulation, Pi deficiency with dampness phlegm, Gan-qi stagnation and Pi deficiency, phlegm stasis accumulation, and Gan Shen insufficiency, which were in accordance with clinical practice. The results of factor analysis indicated that overweight/obesity, abdominal distension, hypochondriac pain, discomfort in the hepatic region were common "condition factors" of fatty liver patients. The 5 "syndrome factors" such as dampness heat accumulation, Pi deficiency with dampness phlegm, Gan-qi stagnation and Pi deficiency, phlegm stasis accumulation, and Gan-Shen insufficiency showed identification significance in syndrome typing. CONCLUSIONS: The basic CM syndrome typings of NAFLD were dampness heat accumulation, Pi deficiency with dampness phlegm, Gan-qi stagnation and Pi deficiency, phlegm stasis accumulation, and Gan-Shen insufficiency. The four parameters of fatty liver patients could be classified by statistical analysis as condition factors and syndrome factors (which could reflect CM syndrome characteristics), which could provide certain evidence for establishing CM syndrome differentiation standards. PMID- 22097200 TI - [Clinical effects of qianggan capsule on the liver tissue pathology and PDGF-BB, TGF-beta1, TIMP-1, and MMP-1 factors in patients with chronic hepatitis B]. AB - OBJECTIVE: To study the therapeutic efficacy of Qianggan Capsule (QC) in treating patients Seventy pa-with chronic hepatitis B fibrosis from the pathological aspect and serum fibrosis markers. METHODS: patients with chronic hepatitis B were randomly assigned to two groups, the treated group (45 cases) and the control group (25 cases). QC was given to patients in the treated group, while glucurone and compound vitamin B were given to those in the control group. The therapeutic course for both groups was 6 months. The therapeutic effect was assessed by determination of fibrosis markers including serum levels of platelet derived growth factor-BB (PDGF-BB), transforming growth factor beta 1 (TGF beta1), matrix metalloproteinases-1 (MMP-1), tissue inhibitors of metalloproteinases-1 (TIMP-1) and serum levels of alanine transaminase (ALT), total bilirubin (TBIL), albumin (ALB), and prothrombin time (PT) were completed 1 month before treatment and at the end of the trial respectively. RESULTS: (1) Serum levels of ALT, TBIL, PT decreased obviously and the serum ALB level obviously increased in both groups (all P<0.05), showing no significant difference between the two groups (P>0.05). (2) Hepatic fibrosis markers: Serum levels of PDGF-BB, TGF-1P3, and TIMP-1 significantly decreased, and serum MMP-1 level markedly increased in the treated group more than before treatment (all P<0.05). No significant difference was shown between before and after treatment in each index of the control group (P>0.05). Serum levels of PDGF-BB, TGF-beta1, and TIMP-1 were obviously lower and the serum MMP-1 level was obviously higher in the treated group than in the control group after treatment (all P<0.05). (3) Hepatic histopathological results: The hepatic inflammatory necrosis activity and the hepatic fibrosis degree in the treated group were significantly improved (P<0.05), with the total effective rate of the hepatic necrosis activity improvement being 40.00% and that of the hepatic fibrosis degree being 57.78%. But there was no obvious improvement in the hepatic inflammatory necrosis activity or the hepatic fibrosis degree in the control group (P>0.05). CONCLUSIONS: QC could effectively improve serological indices and pathological indices of chronic hepatitis B fibrosis patients, showing better therapeutic effect in reversing hepatic fibrosis and alleviating hepatic inflammatory necrosis. PMID- 22097201 TI - [Plasma proteomic analysis of patients with chronic hepatitis B of damp-heat retention in the middle-jiao syndrome]. AB - OBJECTIVE: To study the essence of chronic viral hepatitis B (CHB) of damp-heat retention in the middle-jiao syndrome (DRMS) from plasma proteomic angle. METHODS: Plasma proteomic analyses of plasma whole protein of patients in the group with CHB of DRMS (20 cases) and subjects in the health control group (5 cases) were compared using two-dimensional gel electrophoresis (2-DE), mass spectrography, and other bioinformatics analyses methods. RESULTS: Eight protein dots with obvious regularity changes of differential expression were obtained by 2-DE. Seven protein dots were obtained by mass spectrography (One protein dot with undetected results): apolipoprotein C2 (APO-C2), vitronectin (VN), haptoglobin (HPT), transthyretin (TTHY), APO-A1, serum amyloid P-component (SAMP), and APO-A4. Compared with the health control group, the expressions of APO-A1 and APO-A4 were somewhat higher and the expressions of the expressions of the rest five protein dots were obviously down-regulated. CONCLUSION: APO-Al and APO-A4 were of potential significance in the diagnosis of CHB patients of DRMS, prognostic markers, or treatment targets. PMID- 22097202 TI - [Effect of biantong huangqi ointment combined with western medicine on the recurrence of children's bronchial asthma]. AB - OBJECTIVE: To assess the intervention of Biantong Huangqi Ointment (BHO) combined with Western medicine (WM) on the recurrence of bronchial asthma (BA). METHODS: Eighty-four BA children patients were randomly assigned to the treatment group (43 cases) and the control group (41 cases). During the period of onset, patients in the two groups were treated by WM alone. During the remission phase, patients in the treatment group took BHO, one dose daily, while those in the control group were treated with atomized inhalation of Budesonide and Salbutamol (0.5 mL each time for those 3 -8 years old; 0.75 mL each time for >or=those 8-12 years old). The therapeutic course for them all was 1 month. The serum levels of IgG and IgE before and after treatment, 6 and 12 months after withdrawal of medication were detected in the two groups, and the recurrence rate of BA observed in the two groups. RESULTS: The recurrence rate of the treatment group was obviously lower than that of the control group after withdrawal of medication (9.5% vs 24.4% for 6 months, 14.0% vs 34.1% for 12 months), showing statistical difference between the two groups (P<0.05). The serum IgG level of children patients in the treatment group increased continuously after medication. The high serum IgE level state obtained long-term and effective relief. CONCLUSION: BHO showed favorable anti-recurrent effect on children's BA. Its mechanism might be associated with regulating children's immune system. PMID- 22097203 TI - [Clinical control study on postmenopausal osteoporosis treated with embedding thread according to syndrome differentiation and medication]. AB - OBJECTIVE: To study the therapeutic efficacy of embedding thread according to staging and wholism syndrome differentiation and its effect on correlated indices of patients with postmenopausal osteoporosis. METHODS: 135 patients with postmenopausal osteoporosis were randomly assigned to the control group A (treated with Calcichew D3 Tablet), the control group B (treated with Calcichew D3 Tablet and Xianling Gubao Capsule), and the treatment group (treated with Calcichew D5 Tablet and embedding thread according to staging and wholism syndrome differentiation). The visual analogue scale (VAS), Chinese medicine syndrome integral, and the quality of life scale before treatment, 3 months after treatment, and 6 months after treatment were assessed. Changes of the lumbar bone mineral density (BMD) and the serum level of estradiol (E2) were also assessed before and after six-month treatment. And the therapeutic efficacy of each group was also assessed after 6 months of treatment. RESULTS: Before treatment, there was no significant difference in scores of VAS, Chinese medicine syndrome integral and the quality of life scale, the.serum level of E2, and the lumbar BMD of the patients in three groups (all P>0.05). After three months of treatment, there was significant difference in scores of VAS, Chinese medicine syndrome integral and the quality of life scale of the patients in the three groups (all P<0.01). Of them, the improvement of the three indices in the control group A was the worst in three groups (P< 0.05, P<0.01). The VAS in the treatment group was superior to those in control group B (P<0.01). But the difference of Chinese medicine syndrome integral and the quality of life scale was insignificant in the three groups. After six months of treatment, significant difference was shown in the scores of VAS, Chinese medicine syndrome integral, or the quality of life scale of the patients in the three groups when compared with the corresponding index before treatment and after three months of treatment (all P<0.01). Of them the improvement of the three indices of patients in the treatment group and the control group B was better than that in the control group A (all P<0.01), and the improvement in the treatment group were superior to that in the control group B (P<0.05, P<0. 01). Significant difference was shown in the serum level of E2 and the lumbar BMD of the patients in the treatment group and the control group B when compared with before treatment of the same group (both P<0.01). But there was no difference in the control group A between before and after treatment, with better effects obtained in the treatment group and the control group B. And the serum level of E, of the patients in the treatment group after treatment was higher than that in the control group B (P<0.01), but there was no difference in the lumbar BMD. The therapeutic efficacy in the treatment group and the control group B were superior to that in the control group A (P<0.01, P<0.05), but no difference existed between the treatment group and the control group B. CONCLUSIONS: The therapy of embedding thread according to staging and wholism syndrome differentiation could reduce the scores of VAS and Chinese medicine syndrome integral, enhance the serum lever of E2, the quality of life scale and the lumbar BMD of patients with postmenopausal osteoporosis. So it was an effective method. PMID- 22097204 TI - [Effect of massage on hemodynamics parameters of uterine artery and serum prostaglandin in treating patients with primary dysmenorrhea]. AB - OBJECTIVE: To observe the curative effect of massage in the treatment of primary dysmenorrhea (PD), and its effect on hemodynamics parameters of uterine artery and serum prostaglandins. METHODS: 60 PD patients were randomly assigned to the massage group and the control group, 30 in each. Patients in the massage group received massage, while those in the control group orally took ibuprofen sustained release capsule, both for three menstrual cycles. The pain degree was assessed using visual analogue scale (VAS). The hemodynamics parameters of uterine artery [including pulsatility index (PI), resistance index (RI), systolic to diastolic peak ratio (S/D)], the serum levels of prostaglandin F2alpha (PGF2alpha) and PGE2 in the menstruation were detected in the two groups before and after treatment. RESULTS: There was no statistical difference in each index before treatment between the two groups (P>0.05). Compared with the control group after treatment, the scores of VAS (mm, 33. 17+/-7.93 vs 63.53+/-9.48), PI (2.18+/-0.18 vs 2.74+/-0.23), RI (0.67+/-0.09 vs 0. 86+/-0.27), S/D (5.44+/-0.47 vs 7.56+/-0.28), and serum PGF2a level (ng/L, 28. 10+/-2.41 vs 37.68+/-2.16) were lower and serum PGE, level (ng/L, 29.82+/-2.13 vs 26.43+/-1.42) higher in the massage group, showing statistical difference (P<0.05, P<0.01). CONCLUSIONS: Massage had favorable therapeutic effect on PD. Its effect might be achieved through improving the blood circulation of uterus, adjusting the abnormal levels of PGF2a and PGE2, thus exerting pain relief effect. PMID- 22097205 TI - [A multi-center, randomized control trial on clinical research education to diabetes patients]. AB - OBJECTIVE: To assess the effect of implementing education about clinical research in changing the awareness and attitudes of diabetic patients. METHODS: A randomized control trial was implemented in 258 patients with diabetes from 6 hospitals. The participants were assigned to the intervention group (129 cases, who received education about the clinical research) and the control group (129 cases, who received no intervention). The outcome indicators were the variables on knowledge, attitude for the clinical research between before and after intervention in the same group and between the two groups. RESULTS: There was no withdrawal or lost in the two groups. Comparing the contents between inter-groups and intra-group for 19 assignment questions, it showed statistical significance (P<0.05). After the patients received education, their knowledge about and attitude towards clinical research, informed consent, placebo, follow-up, random allocation, and ethics, etc. were markedly improved. Their attitudes for the participants to join in scientific research, opinion, confidence were obviously changed, and it also showed that the method was feasible. The patients' education level was positively correlated with the clinical research educated outputs. CONCLUSION: This study proved the necessity for patients participating in future clinical trials to receive education, as well as its feasibility and effectiveness. PMID- 22097206 TI - [Experimental study on metabonomics of coronary heart disease myocardial ischemia of blood stasis syndrome based on the NOESY pulse NMR]. AB - OBJECTIVE: To study changes of serum metabolite profiles in Ameriod ring induced coronary heart disease (CHD) chronic myocardial ischemia (CMI) mini-pigs by NMR. METHODS: The blood stasis syndrome (BSS) animal model was established by coronary angiography, blood hemorheology, and so on. By using NMR and pattern recognition, changes of serum endogenous metabolites of the four-week mini-pigs of the BSS model and the sham-operative group. RESULTS: The model prepared by using this method was confirmed as the stable CHD CMI model of BSS. Animals in the model group and the sham-operative group were clearly classified using the principal component analysis (PCA). The PCA of serum 1HNMR spectrum and metabolic spectrum in the two groups were significantly different in this model. Compared with the sham-operative group, endogenous metabolites in the serum such as the levels of citric acid, beta-hydroxybutyrate, gamma-aminobutyric acid, lactic acid, glutamate, glucose, etc. increased in the model group, while the concentrations of lipid metabolites such as low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) decreased. CONCLUSIONS: The different metabolites between the model group and the sham-operative group mainly manifested as metabolic disorders of glucose and lipids, as well as energy metabolism such as the disturbance of tricarboxylic acid (TCA). Metabonomics could provide a new path for the objectivity of Chinese medicine syndromes. PMID- 22097207 TI - [Effect of qufeng zhidong simplified recipe on the behavior of the tic disorder rats]. AB - OBJECTIVE: To study the effects qufeng zhidong Simplified Recipe (QZSR) on the behavior of the tic disorder (TD) rats. METHODS: Fifty male SD rats were randomly divided to the normal group, the model group, the QZSR-1 group, the QZSR-2 group, and the QZSR group, 10 in each group. Two mg/kg apomorphine (APO) was intraperitoneally injected to rats in the model group, the QZSR-1 group, the QZSR 2 group, and the QZSR group, while equal volume of normal saline was intraperitoneally injected to rats in the normal group, both once daily for 7 successive weeks. At the 4th week equal volume of normal saline was intraperitoneally injected to rats in the model group and the normal group, while corresponding medicinal liquid was intraperitoneally injected to those in the rest groups, both once daily for 7 successive weeks. At the 2nd and 4th week of intervention, rats' improvement degrees of stereotyped behavior and the open field test were monitored, and their experimental results were analyzed. RESULTS: At the 2nd and 4th week of intervention, when compared with those of the model group, the score of stereotyped behavior decreased, the numbers of passing-panel, straightening, and dejecta pill were reduced, and the number of grooming increased in the QZSR-1 group, the QZSR-2 group, and the QZSR group. But there was no difference among the three groups (P>0.05). CONCLUSION: QZSR could significantly reduce APO induced stereotyped behavior scores of TD rats, improve their locomotor activities, and reinforce their adaptive faculty. PMID- 22097208 TI - [Effects of chaihu shugan powder on the behavior and expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe in rat model of depression]. AB - OBJECTIVE: To investigate the effects of Chaihu Shugan Powder (CHSGP) on the behavior and the expressions of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptors B (TrkB) in the hippocampus, amygdala, and the frontal lobe of depression model rats. METHODS: Sixty adult Sprague-Dawley rats were randomly divided into 6 groups, i. e., the normal control group (NC), the model control group (MC), the CHSGP group, the disassembly 1 group (CI), the disassembly 2 group (CII), and the Fluoxetine control group (FC), 10 in each group. Except those in the NC, the rest rats were singly housed and exposed on an unpredicted sequence of mild stressor. From the fifteenth day, all rats were administered with equal volume of normal saline (to the NC group and the MC group) and of corresponding medicinal liquid (5.9 g/kg to the CHSGP group, 3.3 g/kg to the CI group, 2.6 g/kg to the CII group, and 1.8 mg/kg to the FC group) by gastrogavage for 2 successive weeks. The rats' body weight, sucrose consumption volume in the sucrose preference test, and times of grooming in the open field test were detected on the 0, 7th, 14th, 21st, 28th day, respectively. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe were detected by immunohistochemical assay and Real-time fluorescent quantitation PCR. RESULTS: Compared with the NC group, the rats' body weight was put up slowly in the MC group. The scores in the open field test decreased. The times of grooming and sucrose consumption volume were both reduced. The time of staying in central square was postponed. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe decreased with statistical significance (P<0.05, P<0.01). Compared with the MC group, the behavior indices of rats in the CHSGP, CI, CII, and FC groups were significantly improved. The mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe were obviously enhanced with statistical significance (P<0.05, P<0.01). CONCLUSIONS: CHSGP could obviously improve the depressive state of the model rats. Its mechanism might be correlated with increasing the mRNA expressions of BDNF and TrkB in the hippocampus, amygdala, and the frontal lobe. PMID- 22097209 TI - [Effects of huanglian jiedu decoction on free radicals metabolism and pathomorphism of the hippocampus in App/PS1 double transgenic mice]. AB - OBJECTIVE: To observe the effects of Huanglian Jiedu Decoction (HLJDT) on the metabolism of free radicals, the morphology and histopathology of hippocampal CA1 neurons in PS1/APP double transgenic mice of Alzheimer's disease (AD), and to study its possible mechanisms, thus providing experimental evidence for treating AD by HLJDT. METHODS: The APP/PS1 double transgenic mouse model was used. Mice were randomly divided into five groups, i. e., the model control group, the positive control group (Aricept), high-, middle-, and low-dose HLJDT group (at the daily dose of 865 mg*kg(-1), 433 mg*kg(-1), and 216 mg*kg(-1), respectively). Corresponding medication was daily given by gastrogavage. Seven months later superoxide dismutase (SOD) and malondialdehyde (MDA) were detected at the ten month old mice, thus observing the effects on the morphology of CA1 hippocampal neurons and the senile plaques (SP). RESULTS: HLJDT and Aricept could obviously increase the SOD contents and lower the MDA contents (P<0.05), attenuate the destroy of neurocytes and the formation of SP, effectively hinder the degeneration of hippocampal neurons. Better results were obtained in the middle dose HLJDT group than in the positive control group (P<0.05). CONCLUSION: The mechanism of HLJDT in treating AD might be possibly correlated with improving anti-oxygenation, protecting hippocampal neurocytes, and reducing the formation of SP. PMID- 22097210 TI - [Effects of berberine on the pancreatic beta cell apoptosis in rats with insulin resistance]. AB - OBJECTIVE: To explore the effects of berberine on the pancreatic 13 cell apoptosis in rats with insulin resistance (IR). METHODS: IR Wistar rat model was established by feeding with high fructose diet. After 6-week treatment of berberine, oral glucose tolerance test (OGTT) was performed. Then fasting insulin level (Fins) was detected and insulin sensitivity index (ISI) calculated. The islet was isolated and purified. The pancreatic p3 cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The apoptosis-related protein ASK1 and Caspase-12 expressions were examined by immunohistochemical assay. RESULTS: Compared with the normal group, the blood glucose at 0 and 1 h increased, the Fins increased and ISI decreased, the blood lipids were disarranged, the pancreatic beta cell apoptosis increased, and ASK1 and Caspase-12 protein expressions increased in IR rats. Compared with the model group, the blood glucose at 0 and 1 h and the Fins decreased, ISI increased, the disarranged blood lipids were improved, the pancreatic beta cell apoptosis decreased, and the ASK1 expression decreased, but with no obvious change in the Caspase-12 expressions in the berberine group. CONCLUSIONS: Berberine could alleviate IR state in IR rats and inhibit pancreatic 13 cell apoptosis. Its mechanism might be correlated with the inhibition of ASK1 protein expressions. PMID- 22097211 TI - [Uniform designed research on the active ingredients assembling of huangqi decoction for inhibition of DMN-induced liver fibrosis]. AB - OBJECTIVE: To screen out effective ingredients of Huangqi Decoction (HQD) on dimethylnitrosamine (DMN) induced liver fibrosis and its assembling actions. METHODS: (1) DMN solution (0. 5%) was peritoneally injected to rats to prepare the liver fibrosis model for 12 times, starting from the 1st day of modeling to the end of the 4th week. Uniform design method with 4-factor 8-level table was used to optimize the proportion of four ingredients from HQD, including astragaloside (AS), astragalus flavonoids (AF), glycyrrhizae acid (GA), and glycyrrhizae flavonoids (GF). Moreover, the changes of hydroxyproline (Hyp) content in the liver issue and the level of alanine aminotransferase (ALT) in serum were observed as screen indices, and the method of regression analysis was used to find out an optimal combination. (2) A further study for comparing and verifying the efficacy of the obtained optimized prescription was conducted by observing the changes of fibrosis pathology, the content of Hyp in the liver tissue and serum enzyme activity after medication. RESULTS: The optimal proportion of AS and GA was 164:48. Compared with the model group, the content of Hyp in the liver tissue and the levels of ALT, aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum decreased significantly, indicating the inhibiting effect of HQD and the AS/GA combination group on hepatic fibrosis formation (P<0.05). The AS/GA combination group was better than AS/GA used alone group in reducing the content of Hyp in the liver tissue and the level of ALT in serum. Furthermore, the AS/GA combination group was better than the HQD group in reducing the level of ALT in serum. CONCLUSIONS: AS and GA were effective ingredients of HQD, and the combination of AS and GA had obvious synergistic effect in reducing liver collagen deposition and decreasing serum ALT activity in DMN-induced liver fibrosis. PMID- 22097212 TI - [Effect of the combination of bushen xuguan recipe and ruanjian huayu recipe on the MMP-2 expression in endometriosis rats]. AB - OBJECTIVE: To observe the effect of the combination of Bushen Xuguan Recipe (BXR) and Ruan-jian Huayu Recipe (RHR) on the matrix metalloproteinases-2 (MMP-2) expression of rats with endometriosis (EMS), and to study the pathogenesis and mechanism of EMS. METHODS: The EMS rat model was established. Successfully modeled female SD rats were randomly divided into the combination group (BXR+RHR), the RHR group, and the model group. And a normal control group was set up. After 4 weeks of medicinal treatment, rats were sacrificed in the oestrus cycle. MMP-2 distribution and the staining density in ectopic and eutopic endometrium of the rats were observed under microscope. The MMP-2 expression was determined by immunohistochemical assay (SP method). RESULTS: The MMP-2 expression in the ectopic endometrial tissues of rats in the model group were significantly higher than that of the normal control group (P<0.01). Compared with the model group, the MMP-2 expression decreased in the combination group and the RHR group (P<0.05). The therapeutic effect of the combination group was most obvious by observing the distribution of MMP-2 and changes of positive staining. CONCLUSIONS: The occurrence of EMS was correlated with increased activities of MMP-2. The combination method could inhibit the activities of MMP-2 in the ectopic endometrial tissues of EMS rats more effectively than RHR alone, which might be achieved through improving the endocrine environment, and reducing the "invasion" capability of the ectopic endometrium. PMID- 22097213 TI - [Inhibitory effect of arsenic trioxide on the pulmonary metastasis of melanoma B16 cells]. AB - OBJECTIVE: To study the inhibitory effect of arsenic trioxide (As2O3) on the pulmonary metastasis of melanoma B16 cells. METHODS: Mice melanoma cells B16 were injected into the vein of the eye socket of C57BL/6J mice. The lung tissue weight and the B16 melanoma lung metastasis nodules were examined after intraperitoneal injection of As2O3. The microvessel density in the pulmonary metastatic tumor nodules was observed using HE staining and immunohistochemistry analysis for VIII R Ag. The cell adhesion rate was detected using CellTiter 96 Aqueous One reagent. RESULTS: As2O3 could significantly inhibit the pulmonary metastasis of B16 melanoma. The lung weight, the pulmonary metastasis nodules, and microvessels per visual field of the experimental group and the control group were 0.139+/-0.013 g and 0.353+/-0.070 g, 20.42+/-1.78 and 61.42+/-3.09, 3.25+/-0.75 and 7.50+/-1.45, respectively (all P<0.01). As2O3 showed significant effect on the cell adhesion rate, showing statistical difference between the two groups (P<0.01). CONCLUSIONS: As2O3 had significant antitumor metastasis effect. It might be correlated with inhibiting angiogenesis and enhancing the cell adhesion. PMID- 22097214 TI - [Effect of salvianolic acid B on TGF-beta1-induced human embryonic lung fibroblast's biological behavior]. AB - OBJECTIVE: To investigate the effect of salvianolic acid B (SAB) on the proliferation of human embryonic lung fibroblast MRC-5, and the secretion of procollagen I and endogenous transforming growth factor-beta1, (TGF-beta1). METHODS: The MRC-5 cells were randomly divided into four groups as follows: the control group: cells cultured with DMEM but with no TGF-beta1, or SAB; the TGF beta1, group: cell cultured with 10 ng/mL TGF-beta1; the SAB1 group: cell cultured with medium with 10 ng/mL TGF-beta1 and 1 pmol/L SAB; the SAB2 group: cell cultured with medium with 10 ng/mL TGF-beta1, and 10 pmol/L SAB. The proliferation of cells was assayed by MTT incorporation. The concentration of amino-terminal propeptide of type I procollagen (PINP), a marker of collagen synthesis, was measured by radioimmunoassay. The endogenous TGF-beta1, levels were measured using ELISA. RESULTS: The optical density, procollagen I contents, and endogenous TGF-beta1, levels significantly increased when compared with those of the control group (P<0.05). Compared with the TGF-beta1, group, the optical density was obviously lowered, the procollagen I contents and endogenous TGF beta1, levels significantly decreased in the SAB1 group and the SAB2 group, and better in the SAB2 group, showing statistical difference (P<0.05). CONCLUSIONS: SAB could inhibit the proliferation of MRC-5 cells induced by TGF-beta1 and attenuate the roles of secreting collagen and endogenous TGF-beta1. It had the potential of postponing or delaying the progressive developing of pulmonary fibrosis. PMID- 22097215 TI - [Effect of genistein on MAPK signal pathway in the collagen-induced arthritis fibroblast-like synoviocytes]. AB - OBJECTIVE: To study the effect of genistein (Gen) on MAPK signal pathway in the CIA rat fibroblast-like synoviocytes (FLS). METHODS: The rat model of collagen induced arthritis (CIA) was established. The cultured FLS of CIA rats were divided using randomized method. The effects of Gen (at the concentration of 50, 100, and 200 micromol/L, respectively) on the proliferation of FLS in CIA rats using methyl thiazolyl tetrazolium (MTT) assay. Effects of Gen (at the concentration of 50, 100, and 200 pmol/L, respectively) on the expressions of extracellular signal-regulated kinase (ERK) and phosphorylated extracellular signal-regulated kinase (p-ERK) in the FLS of CIA rats were detected. RESULTS: Gen could inhibit the proliferation of FLS in CIA rats. The FLS proliferation in the high dose Gen group at 72 h was only 1.10+/-0.04, significantly lower than that in the model group (2.12+/-0.03, P<0.01). Besides, after Gen's action on FLS, the expression of p-ERK was down-regulated. It was only 0.34+/-0.02 in the high dose Gen group, significantly lower than that in the model group (2.68+/ 0.14, P<0.01). There was no change in the expression of ERK (P>0.05). CONCLUSIONS: Gen could inhibit the proliferation of FLS in CIA rats. Its mechanism of action was mainly correlated to down-regulating the tyrosine kinase of MAPK signal transduction pathway and inhibiting phosphorylation of ERK. PMID- 22097216 TI - [Exploration on the establishment of animal models for gouty nephropathy complicated with chronic renal failure]. AB - OBJECTIVE: To explore the method for establishing animal models of gouty nephropathy complicated with chronic renal failure. METHODS: Six-eight weeks old male Wistar rats were fed with 10% fodder yeast. The adenine at the daily dose of 100, 150, 200, 250, and 300 mg/kg was administrated to them by gastrogavage. The serum levels of blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) were dynamically monitored. Meanwhile, the pathological changes of rat kidney were observed. RESULTS: Compared with the normal control group, serum BUN, Cr, and UA obviously increased in rats administered with 100 mg/kg for 7 days (P<0.05). Meanwhile, pathological changes as gouty nephropathy occurred. Along with the prolongation of the modeling time, the aforesaid biochemical indices and pathohistological changes of the kidney were more obvious. The blood Cr level just reached the chronic renal failure level on the 26th day of the administration (about the 4th week), and obviously exceeded the renal failure level on the 41st day (about the 6th week). The blood UA level increased to a higher level on the 7th day of modeling, and maintained at a higher level for a long time. It decreased rapidly from the 41st day to the 48th day. The renal pathological examination showed aggravated infiltration of lymphocytes and stromal fibrous proliferation. On the 48th day of modeling, the proliferation of the fibrous tissue and the interstitial fibrosis were obvious on the bases of the aforesaid changes. The serum BUN, Cr, and blood UA obviously increased in the rats administered with 150, 200, 250, and 300 mg/kg when compared with the normal control group, reaching the level of chronic renal failure (P<0.05). These levels obviously decreased 17 days after restoring to normal fodder feeding, and approached the normal levels till the 35th day. CONCLUSION: Ideal experimental animal models of gouty nephropathy complicated with chronic renal failure could be established in male Wistar rats by feeding with 10% fodder yeast and 100 mg/kg adenine by gastrogavage for 5 weeks. PMID- 22097217 TI - [Preventive and therapeutic effects of xiaobanxia fuling decoction on cisplatin induced pica rats]. AB - OBJECTIVE: To investigate the preventive and therapeutic effects of Xiaobanxia Fuling Decoction (XBFD) on cisplatin-induced pica rats and to study its mechanism. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into the following 7 groups, i.e., the blank control group, the model group, the high , middle-, and low-dose XBFD groups (at the daily dose of 30, 15, and 7. 5 g/kg, respectively), the aprepitant (at the daily dose of 13 mg/kg), and pure Chinese medicine group (at the daily dose of XBFD 15 g/kg), 6 in each group. On the 3rd day of this study, 3 mg/kg cisplatin was intraperitoneally injected to rats except the blank control group and the model group to establish the pica rat model. The consumptions of kaolin, food, and the general situation of rats were observed. The protein and mRNA expressions of neurokinin 1 receptor (NK1R) in both the medulla oblongata and the gastric antrum were measured by immunohistochemical assay and Real-time fluorescent quantitative PCR respectively on the sixth day of this study. RESULTS: On the third, fourth, and fifth day of this study, the consumption of kaolin of rats significantly increased when compared with the blank control group (P<0.01). Compared with the model group, the consumption of kaolin significantly decreased in the high-, middle-, and low dose XBFD groups on the third, fourth, and fifth day of this study (P<0.05). The food intake of rats in the high-dose XBFD groups significantly increased when compared with the model group on the third day of this study (P<0.05). The protein and mRNA expressions of NK, R in the medulla oblongata and the gastric antrum significantly decreased in the high- and middle-dose XBFD groups when compared with the model group (P<0.05). CONCLUSIONS: XBFD could prevent and treat cisplatin-induced pica in rats. Its effect might be correlated with decreasing expressions of NK, R in the medulla oblongata and the gastric antrum. PMID- 22097218 TI - [Exploration on syndrome differentiation standardization of Chinese medicine diagnosis and treatment]. AB - The syndrome differentiation standardization of Chinese medicine and treatment technologies is the premise of Chinese medicine's entry into the world. But its individualized diagnosis and therapeutic features are contrary to the specification of standardization. The achievement and existent problems in syndrome differentiation standardization of Chinese medicine and treatment technologies were summarized in this paper. The thinking ways and recommendations to solve were proposed as well. PMID- 22097219 TI - [Chinese medicine prevention and treatment of AIDS in terms of constitution theory]. AB - The significant effects of constitutional factor on AIDS were addressed. Acquired immunodeficiency syndrome (AIDS), caused by HIV, is mainly characterized as decreased immune function or immune deficiency. It has strong infectiousness and higher mortality, so it is one of the diseases that attract great attention to clinical prevention and treatment. The constitution not only exerts significant effect on the immune function of patients with AIDS, but also plays important roles in the development, prognosis, and outcomes of AIDS. Therefore, it is of great referential significance in both clinical and scientific studies of AIDS by exploring Chinese medicine prevention and treatment of AIDS from the angle of constitution. PMID- 22097220 TI - [Study on the social communication features of interpretation of Chinese medicine]. PMID- 22097221 TI - [Severe sensorineural deafness after cerebral trauma by electroacupuncture and scalp acupuncture: a report of 19 cases]. PMID- 22097222 TI - [Treatment of declined ovary reserve function by shen nourishing blood activating method: a case report of 50 cases]. PMID- 22097223 TI - [Overview of adverse effects of integrative medicine treatment of social communication stress on bronchial asthma]. PMID- 22097224 TI - [Advance of Chinese medicine studies on children's mycoplasmal pneumonia]. PMID- 22097225 TI - IMAJ "Bat Mitzvah" year: highlights of 2010-2011. PMID- 22097226 TI - Severe influenza A (H1N1): the course of imaging findings. AB - BACKGROUND: An outbreak of respiratory illness caused by a novel swine-origin influenza virus (influenza A/H1N1 2009) that began in Mexico was declared a global pandemic by the World Health Organization in June 2009. The pandemic affected many countries, including Israel. OBJECTIVES: To compare the course of chest radiographic and computed tomography findings in patients who survived and those who died following admission to the intensive care unit (ICU) or intubation due to severe laboratory-confirmed swine-origin influenza A/H1N1 2009. METHODS: We retrospectively reviewed the patient records (267 radiographs, 8 CTs) of 22 patients (10 males, 12 females) aged 3.5-66 years (median 34) with confirmed influenza A/ H1N1 2009, admitted to the ICU and/or intubated in five major Israeli medical centers during the period July-November 2009. We recorded demographic, clinical, and imaging findings--including pattern of opacification, extent, laterality, distribution, zone of findings, and presence/absence of nodular opacities--at initial radiography and during the course of disease, and compared the findings of survivors and non-survivors. Statistical significance was calculated using the Wilcoxon (continuous variables) and Fisher exact tests. RESULTS: The most common findings on the initial chest radiography were airspace opacities, which were multifocal in 17 patients (77%) and bilateral in 16 (73%), and located in the lower or lower and middle lung zones in 19 patients (86%). Large airspace nodules with indistinct margins were seen in 8 patients (36%). Twelve patients survived, 10 died. Patients who died had multiple background illnesses and were significantly older than survivors (P = 0.006). Radiologic findings for the two groups were not significantly different. CONCLUSION: Airspace opacities, often with nodular appearance, were the most common findings among patients with severe influenza A/H1N1 2009. The course of radiologic findings was similar in patients with severe influenza A/ H1N1 2009 who survived and those who died. PMID- 22097227 TI - Endoscopic transnasal cerebrospinal fluid leak repair: a 10 year experience. AB - BACKGROUND: Endoscopic techniques have gained popularity for the repair of anterior skull base defects. OBJECTIVE: To describe the 10 year experience with endoscopic surgical repair of cerebrospinal fluid (CSF) rhinorrhea in a tertiary medical center. METHODS: The files of all patients who underwent endoscopic transnasal CSF leak repair in our institution between 1996 and 2006 were reviewed. RESULTS: Twenty-four patients were identified: 16 women and 7 men with a mean age of 48 years and one child aged 9.5 years. The leak was trauma-induced in 17 patients and occurred spontaneously in the other 7. The defect was localized by preoperative computed tomography or CT/cysternography in 86% of cases. A fascia lata graft was the dominant choice for defect closure, and it was combined with a conchal or septal flap, fat, periosteum, or fibrin glue in 15 patients. The success rate was 83% after the first closure attempt and 91% after the second. Two patients required a craniotomy at the third attempt. Mean hospitalization time was 6.7 days. There were two minor complications. Two patients were lost to follow-up; none of the others had a recurrence during 2 years of follow-up. CONCLUSIONS: The endoscopic transnasal technique for the repair of CSF rhinorrhea is associated with a high success rate and low morbidity, and it should be considered for the majority of cases. Repeated attempts may improve success. PMID- 22097228 TI - Periprocedural complication rate of carotid endarterectomy versus carotid angioplasty and stenting: a retrospective study and review of the literature. AB - BACKGROUND: In the past, carotid endarterectomy (CEA) was the only modality for invasive intervention in cases of carotid stenosis. Due to improvements in endovascular techniques (stenting), there is a growing debate regarding the preferred procedure for carotid intervention. OBJECTIVES: To compare the 30 day complication rate after CEA and carotid angioplasty and stenting (CAS) in a tertiary medical center in Israel between the years 2008 and 2010. METHODS: We reviewed the medical charts of all the patients who underwent either CEA or CAS of the internal carotid artery due to symptomatic and asymptomatic stenosis during the period 2008-2010 (total of 128 patients). RESULTS: There was no difference between the groups in the rate of severe complications in the peri procedural period. Mild complications were non-significantly more common in the CEA group (17%) compared to the CAS group (7.1%). CONCLUSIONS: There was no significant difference in the mild and severe complications rate between CEA and CAS in the peri-procedural period. PMID- 22097229 TI - Inducible clindamycin resistance among methicillin-sensitive Staphylococcus aureus infections in pediatric patients. AB - BACKGROUND: Staphylococcus aureus infections are a major cause of morbidity and mortality worldwide. Clindamycin is widely used in the treatment of staphylococcal infections; however, it is our impression that in the last few years, inducible clindamycin resistance (ICR) has become more prevalent. OBJECTIVE: To assess the prevalence of ICR in methicillin-sensitive Staphylococcus aureus (MSSA) infections among pediatric patients in Israel. METHODS: We reviewed the files of children diagnosed with MSSA infections during the period January 2006 to June 2007 forfull antibiogram (includingthe D-test for ICR), phage typing and randomly amplified polymorphic DNA. RESULTS: Altogether, 240 MSSA isolates were recovered, mainly from wounds and abscesses. ICR was detected in 62 of 68 erythromycin-resistant/clindamycin-sensitive strains (91%); the ICR rate for the total number of isolates was 26% (62/240). Phage type analysis demonstrated that 38 of 61 ICR isolates (62%) were sensitive to group 2, compared to 42 of 172 isolates (24%) that did not express ICR (P < 0.01). On randomly amplified polymorphic DNA, phage type 2 isolates expressing ICR belonged to the same clone, which was different from ICR isolates sensitive to other phages and from isolates not expressing ICR. CONCLUSIONS: Inducible clindamycin resistance is common among methicillin-sensitive Staphylococcus aureus in Israeli children. The D-test should be performed routinely in all MSSA isolates. PMID- 22097230 TI - Optimal time needed for withdrawal of mechanical ventilation in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are a major problem worldwide and are usually the main indication for mechanical ventilation (MV), especially in the intensive care unit (ICU). The rate of weaning failure is also high and prolonged MV leads to complications of intubation. The goal is to wean these patients as soon as possible. OBJECTIVE: To determine the optimal time necessary to start the weaning process. METHODS: In an attempt to determine the length of MV and stay in the ICU, we compared the length of MV, weaning, reintubations and discharge during a 10 month period. This study included 122 patients on MV due to severe exacerbation of COPD who were not suitable for non-invasive ventilation. For each patient serial arterial blood gases were measured at admission and during hospitalization. PeCO2 (mixed expired CO2) was tested using a Datex S/5 instrument at follow-up. RESULTS: The study population comprised all patients who required MV; of these 122, 108 were ventilated from 6 to 140 hours (mean 48 +/- 42), 9 needed more than 168 hours, and 5 died due to severe ventilation-associated pneumonia. No correlation was found between pH, PCO2 and length of MV; these findings did not contribute to evaluation of the patient's condition nor did they enable us to predict the length of treatment necessary. CONCLUSION: Most of the patients (93%) ventilated for acute respiratory failure due to COPD required MV for only 6-90 hours. PMID- 22097231 TI - Religiosity, anxiety and depression among Israeli medical students. AB - BACKGROUND: Religiosity has been examined as a mechanism of stress management. Since many studies have shown a high rate of psychological morbidity among medical students during different stages oftraining, it is important to investigate whether religiosity may serve as a protective factor. OBJECTIVES: To assess the association between religiosity and depression or anxiety in a sample of medical students and to compare the results with a matched sample of students from other fields of study. METHODS: This cross-sectional study examined a sample of Tel Aviv University medical students and compared them with students in other faculties at the same university for any association between religiosity and depression or anxiety. The subjects completed the Beck Depression Inventory, the Beck Anxiety Inventory, a modified religiosity inventory, and a demographic and psychosocial variables inventory. RESULTS: Findings did not show a significant association between religiosity and depression or anxiety in the general sample (n = 119). A positive significant correlation between religiosity and anxiety was found among medical students, with 29.4% of them reporting anxiety and 25.2% depression. While high rates of depression and anxiety were reported by students in the first to third years (preclinical years), there was a decrease in depression and anxiety in the fourth to sixth years (clinical years). However, higher anxiety and depression scores were noted among controls as compared to medical students. CONCLUSIONS: In contrast to another recent investigation, a negative correlation between religion and depression/anxiety does not necessarily exist. An association between religiosity and mental health could have many theoretical and practical implications and requires further investigation. Similar to previous studies, the rates of depression and anxiety among Israeli medical students were comparable with those of other countries. These rates are considered higher than those in the general population and emphasize the importance of alertness to mental health issues among students, especially during the early study years. PMID- 22097232 TI - Does percutaneous transluminal renal artery angioplasty improve blood pressure control and renal function in patients with atherosclerotic renal artery stenosis? AB - BACKGROUND: Percutaneous angioplasty (PTA) and stenting is an established procedure for the treatment of hypertension caused by atherosclerotic renal artery stenosis. However recently, the decision whether or notto perform this procedure has raised considerable debate. OBJECTIVES: To examine the association between the basic clinical and radiological characteristics of candidates for renal artery PTA and the clinical outcome of the procedure in terms of improvement of blood pressure control and renal function. METHODS: We conducted a retrospective cohort study of all patients who underwent percutaneous transluminal renal artery angioplasty (PTRA) and stent implantation in a tertiary medical center during the period 2000-2007. The clinical and radiological data were extracted from the medical file of each patient. Blood pressure measurements and creatinine level were recorded before the procedure and 1 month, 6 months, 12 months and 18 months after PTRA. RESULTS: Thirty-two patients were included in the final statistical analysis. The mean age of the study population was 66.6 +/- 8.8 years old and 75% were men. There was a significant reduction in both systolic and diastolic blood pressure 1 month after the procedure: 160.5 +/- 24.7 vs. 141.8 +/- 23.6 mmHg and 83.8 +/- 12.9 vs. 68.8 +/- 11.8 mmHg respectively (P < 0.001). The reduction in blood pressure was constant throughout the follow-up period and was evident 18 months after the procedure: 160.5 +/- 24.7 vs. 135.0 +/ 35.1 mmHg and 83.8 +/- 12.9 vs. 71.3 +/- 16.5 mmHg respectively (P < 0.001). However, no improvement in renal function was observed at any time during the follow-up period. We could not demonstrate an association between clinical or radiological features and the clinical outcome after PTRA. CONCLUSIONS: Our findings show that PTRA can be considered an effective procedure for improving blood pressure control in patients with atherosclerotic renal artery stenosis (ARAS) and resistant hypertension. This research, together with previous studies, strengthens the knowledge that the decline in glomerular filtration rate seen in many patients with ARAS is non-reversible and is not improved by PTRA. PMID- 22097233 TI - The genetics of benign neutropenia. AB - In Israel, Yemenite Jews and other populations including Ethiopian Jews and Bedouins have a low neutrophil count. This phenomenon has been called "benign neutropenia" since it has not been associated with any increased risk of infection and has also been described in other populations around the world including Africans, African Americans and Afro-Carribeans. Here we describe the recent success in mapping the gene that underlies benign neutropenia in African American populations. We discuss the known function of the gene and consider potential mechanisms for the effect on neutropenia. We also consider the possibility that this gene underlies the same effect observed in Yemenite Jews, Ethiopian Jews and Bedouins in Israel. PMID- 22097234 TI - Pericardial cyst: a novel extrarenal manifestation of autosomal dominant polycystic kidney disease. PMID- 22097235 TI - Dysferlinopathy and very-long-chain acyl coenzyme A dehydrogenase deficiency segregating in the same family. PMID- 22097236 TI - Primary cardiac lymphoma presenting with atrial fibrillation. PMID- 22097238 TI - Awake fiberoptic intubation and general anesthesia in a parturient with mirror syndrome and a predicted difficult airway. PMID- 22097237 TI - Liver metastasis from colonic adenocarcinoma presenting as nephrolithiasis: computed tomography findings. PMID- 22097239 TI - "Broken heart syndrome" (Takotsubo cardiomyopathy). PMID- 22097240 TI - Usefulness of 64-slice computed tomography for evaluation of atrial septal aneurysm. PMID- 22097241 TI - Local iron overload in chronic leg ulcers. PMID- 22097242 TI - Soluble transferrin receptors (sTfR) for iron deficiency detection in the acutely ill, hospitalized patients. PMID- 22097243 TI - [A squeeze approach for electrocardiogram ST-segment detection based on R-wave and T-wave]. AB - ST-segment is the main clinical appearance in myocardial ischemia detection based on electrocardiogram (ECG) signals. However, it is highly sensitive to interferences (baseline wandering, postural changes, electrode interference, etc.), which cause the feature points of ECG ST-segment to be difficult to detect accurately. Currently, the common detection methods of ST-segment are: R+x and J+x, but they are affected badly by T-wave morphological variability and J point location. For these reasons, firstly we proposed a convenient and accurate approach for T-wave onset in this paper. It did not need to locate T-wave peak and was robust to baseline wandering and T-wave morphology. Secondly, we proposed a squeeze approach for ST-segment detection based on R-wave peak and T-wave onset. After the Long-Term ST database (LTST) verification, the proposed method has shown a good timeliness and robustness, and the accuracy of ST-segment detection has reached above 92%. PMID- 22097244 TI - [Extraction of AF signal during atrial fibrillation from single-lead ECG based on non-stationary heartbeat series]. AB - The real-time and wireless mobile has become the trend of electrocardiogram (ECG) monitoring system for atrial fibrillation (AF). At present, the ECG with multi leads (12 leads) is needed by most of AF signal extraction algorithms in order to extract effective AF waves. However, it is not very convenient for patients' movements in a multi-lead ECG monitoring system. Although the traditional template matching method is for single-lead ECG extraction, it is less robust than blind source extraction algorithm, and is affected severely by noise. In view of this,we put forth a new real-time algorithm for extracting AF from the singlelead ECG, using non-stationary heartbeat series during AF to extend dimension (segmentation), and then applying a blind source extraction algorithm to extract the effective AF signal. Experiment results showed that this method could be used to extract AF signal effectively from a single-lead ECG data. Therefore, it is suitable to apply this method to Wireless Monitoring System using single-lead ECG. PMID- 22097245 TI - [Features of Debakey III aortic dissection after endovascular graft exclusion: evaluation with DSCT angiography]. AB - The purpose of this study was to evaluate the prothesis and vascular features of Debakey III aortic dissection by DSCT angiography after endovascular graft exclusion. We performed a retrospective analysis of 39 Debakey III aortic dissection patients who underwent DSCT angiography after endovascular graft exclusion. After the operations in this study, all the 39 patients had no stent fracture and migration, 15 among all the 39 had endoleaks (type I 12 patients, type II 2 patients, 1 patient had no reason), 17 had large amount of thrombosis in false lumen, and 1 had false lumen outside the stent absorbed completely. While before the operations, 15 patients had abnormal renal perfusion pre operation, and 9 of them had recovered after the operations. And the nearer located to the initial exclusive place, the more obviously the aortic remodeling occurred. In conclusion, DSCT angiography can accurately evaluate the prosthesis and anatomic-pathologic features of Debakey III aortic dissection after endovascular graft exclusion. PMID- 22097246 TI - [An algorithm of corneal reconstruction based on precise location of corneal center]. AB - Placido disk is widely used in corneal topography. In order to solve the problem that the convex of the corneal can not be precisely located in the Placido corneal topography system, an algorithm of corneal reconstruction based on the Placido disk was introduced. The key of this method is the calculation of radius of corneal convex by using the innermost ring data. Based on image analysis result, we precisely calculated the radius of corneal convex iteratively by connecting the convex and the first ring using a circle, and then calculated the location of all the reflect point and its power. At last we created the pseudo color map of the human corneal. The corneal was simulated by using standard steel sphere, and the calculating errors of the result were all below 0.25D. It showed that the algorithm used in this work could get relatively accurate powers and would have fair stability. PMID- 22097247 TI - [Interface interconnection and data integration in implementing of digital operating room]. AB - The digital operating-room, with highly integrated clinical information, is very important for rescuing lives of patients and improving quality of operations. Since equipments in domestic operating-rooms have diversified interface and nonstandard communication protocols, designing and implementing an integrated data sharing program for different kinds of diagnosing, monitoring, and treatment equipments become a key point in construction of digital operating room. This paper addresses interface interconnection and data integration for commonly used clinical equipments from aspects of hardware interface, interface connection and communication protocol, and offers a solution for interconnection and integration of clinical equipments in heterogeneous environment. Based on the solution, a case of an optimal digital operating-room is presented in this paper. Comparing with the international solution for digital operating-room, the solution proposed in this paper is more economical and effective. And finally, this paper provides a proposal for the platform construction of digital perating-room as well as a viewpoint for standardization of domestic clinical equipments. PMID- 22097248 TI - [CUDA-based fast dose calculation in radiotherapy]. AB - Dose calculation plays a key role in treatment planning of radiotherapy. Algorithms for dose calculation require high accuracy and computational efficiency. Finite size pencil beam (FSPB) algorithm is a method commonly adopted in the treatment planning system for radiotherapy. However, improvement on its computational efficiency is still desirable for such purpose as real time treatment planning. In this paper, we present an implementation of the FSPB, by which the most time-consuming parts in the algorithm are parallelized and ported on graphic processing unit (GPU). Compared with the FSPB completely running on central processing unit (CPU), the GPU-implemented FSPB can speed up the dose calculation for 25-35 times on a low price GPU (Geforce GT320) and for 55-100 times on a Tesla C1060, indicating that the GPU-implemented FSPB can provide fast enough dose calculations for real-time treatment planning. PMID- 22097249 TI - [Noise and speckle reduction in ultrasound Doppler blood flow spectrograms by using MP-PCNN]. AB - To reduce background noise and Dopplar speckle in the spectrogram of ultrasound Doppler blood flow signals, a novel method, called Matching Pursuit with threshold decaying pulse coupled neural network (MP-PCNN), has been proposed. The proposed method used an iterative algorithm, which decomposed the ultrasound Doppler signals into linear expansion of atoms in a time-frequency dictionary by using the Matching Pursuit (MP) for de-noising the ultrasound Doppler signal. Subsequently, a simplified unidirectional pulse coupled neural network was applied to calculate the firing matrix of the denoised spectrogram. The Doppler speckles were located and removed through analyzing and processing the PCNN firing matrix. Experiments were conducted on simulation signals which SNRs were 0dB, 5dB and 10dB. The result showed that the MP-PCNN performed effectively in reducing noise, eliminating Doppler speckles, and achieved better performance than exiting noise and speckle suppression algorithm for Doppler ultrasound blood flow spectrogram. PMID- 22097250 TI - [EEG signal classification based on EMD and SVM]. AB - The automatic detection and classification of EEG epileptic wave have great clinical significance. This paper proposes an empirical mode decomposition (EMD) and support vector machine (SVM) based classification method for non-stationary EEG. Firstly, EMD was used to decompose EEG into multiple empirical mode components. Secondly, effective features were extracted from the scales. Finally, the EEG was classified with SVM. The experiment indicated that this method could achieve good classification result with accuracy of 99 % for interictal and ictal EEGs. PMID- 22097251 TI - [Bionic model for coordinated head-eye motion control]. AB - The relationships between eye movements and head movements of the primate during gaze shifts are analyzed in detail in the present paper. Applying the mechanisms of neurophysiology to engineering domain, we have improved the robot eye-head coordination. A bionic control strategy of coordinated head-eye motion was proposed. The processes of gaze shifts are composed of an initial fast phase followed by a slow phase. In the fast phase saccade eye movements and slow head movements were combined, which cooperate to bring gaze from an initial resting position toward the new target rapidly, while in the slow phase the gaze stability and target fixation were ensured by the action of the vestibulo-ocular reflex (VOR) where the eyes and head rotate by equal amplitudes in opposite directions. A bionic gaze control model was given. The simulation results confirmed the effectiveness of the model by comparing with the results of neurophysiology experiments. PMID- 22097252 TI - [Research on the application of pattern selection algorithm based on bioinformatic data]. AB - Pattern selection plays an important role in data mining and pattern recognition, especially for large scale bioinformatic data. There are many problems in this field, such as algorithm complexity and numbers of the best feature subset. In this paper, we propose a new pattern selection algorithm, carrying out pattern selection base on Mutual Information (MI). Pattern subset evaluation index was studied to ensure the best feature subset. To pattern selection, algorithm bases on the correlation of patterns and label, as well as the redundancy of each pattern. Neurofuzzy Pattern Subset Evaluation Index was researched to make sure which is the best subset for our pattern subset evaluation. To verify the effectiveness of our method, several experiments are carried out on the data of gene expression of mouse from Leiden University and UCI datasets. The experimental results indicated that our algorithm achieved better results in the complexity and accuracy. PMID- 22097253 TI - [Wavelet modulus maxima of multifractality based analysis of the pathological ECG signals]. AB - In this paper, wavelet moudulus maxima based multifractal analysis was used to study the multifractal characteristics of the atrial premature beat (APB) signal, the premature ventricular contraction (PVC) signal and normal ECG signal. By analyzing the multifractal spectrum, it was obtained that three kinds of signals had different multifractal strengths. Normal ECG signals had the strongest singularity strength. The PVC beats had the second stronger singularity strength. And the APB beats had the weakest singularity strength. The T test indicated that above-mentioned analysis could disclose significant differences among these three signals. It has meaningful reference for clinical diagnosing and distinguishing with PVC and APB signals. PMID- 22097254 TI - [Finite element analysis of the dynamic behaviour of a microbubble within a rigid micro-tube]. AB - The dynamic behaviour of a microbubble confined within a rigid micro-tube was studied using finite element method. The results indicated that the microbubble oscillation was limited when constrained within the micro-tube. Both the expansion ratio of its effective radius and natural frequency decreased with the decrease of the tube radius. Meanwhile, the deformation of the microbubble was non-spherical and became more significant when the ultrasound pressure amplitude increased. The dynamic behaviour in micro-tube was different from that in infinite liquid. PMID- 22097255 TI - [Extraction method of the visual graphical feature from biomedical data]. AB - The vector space transformations such as principal component analysis (PCA), linear discriminant analysis (LDA), independent component analysis (ICA) or the kernel-based methods may be applied on the extracted feature from the field, which could improve the classification performance. A barycentre graphical feature extraction method of the star plot was proposed in the present study based on the graphical representation of multi-dimensional data. The feature order question of the graphical representation methods affecting the star plot was investigated and the feature order method was proposed based on the improved genetic algorithm (GA). For some biomedical datasets, such as breast cancer and diabetes, the obtained classification error of barycentre graphical feature of star plot in the GA based optimal feature order is very promising compared to the previously reported classification methods, and is superior to that of traditional feature extraction method. PMID- 22097256 TI - [Regularized inhomogeneity correction method for phased array image in magnetic resonance imaging]. AB - Phased array coils (multiple receiver coil systems) have been extensively used for acquisition of MR images owing to their ability of increasing SNR, extending field-of-view (FOV), and reducing acquisition time. But the SOS algorithm,which is main method for phased array image reconstruction,will cause inhomogeneity in reconstructed image. A regularized least square method for phased array image combination is proposed in this paper. In the method, an additional reference scan is performed in advance. By using the reference scan, coil sensitivity map can be acquired, and image reconstructed from reference scan can be used as reference data in the regulation term. Experiments showed that the image uniformity was greatly improved by this method with scanning phantom and volunteer. PMID- 22097257 TI - [The establishment and meaning of the three-dimensional finite element model of pelvic floor levator ani muscle in an old healthy woman]. AB - This paper is to establish a three-dimensional finite element model (3D-FEM) of pelvic floor levator ani muscles in an old healthy women. We acquired the image data of the pelvic bones and pelvic floor muscles from CT and MRI scanning in a non-pregnant old healthy female volunteers. The 3-D reconstruction and mesh optimization of the whole pelvic bones and muscles with application of image processing software Mimics12.0 and Geomagic9.0 were obtained. Then we built the 3D-FEM of the musculoskeletal system of the pelvic bones and levator ani muscles with Ansys11.0 software. We obtained an accurate 3D-FEM of pelvic bones and levator ani muscles in the older healthy woman. The results showed that it was reliable to build 3D-FEM with CT and MRI scanning data and this model could vividly reflect the huge space anatomy of the real pelvic floor levator ani muscles. It avoids the defects to gain the model from the body of anatomical specimens in the past. The image data of model are closer to vivisection, and the model is more conducive to the latter finite element analysis. PMID- 22097258 TI - [The specification of parameters driven by measurement data in the construction of virtual sources in Monte Carlo simulation]. AB - Dose calculation algorithms based on the Monte Carlo (MC) method are widely regarded as the most accurate tool available in radiotherapy. The MC simulation in radiotherapy has been split into two parts, the radiation source simulation and patient simulation. In this research, a virtual source for simulating the linear accelerator head was constructed with measurement-driven models. The dependence between the calculation accuracy and the specification of various parameters was studied by comparison between the measurement data and calculation results. It has been shown that the dose profile obtained by MC simulation can be consistent with measurement data, suggesting that the compound effect of primary photons and secondary photons are considered with appropriate parameter specification. The requirement of modeling for MC simulation can be met in clinical conditions. PMID- 22097259 TI - [Design of extracorporeal apparatus of capsule endoscopy based on ARM+FPGA]. AB - Considering that the patients would bear the annoyance of fixed posture for long time when they are examined with gastrointestinal wireless endoscopy, even though portable devices have been developed, the treatments still depend on PC so much, we proposed an embedded solution based on ARM + FPGA. It used embedded ARM9 S3C2440 as processor core, collected images from digestive tract through capsule endoscopy which can be swallowed down there, and wirelessly transferred these images to the receiving system, then used video decoder chip SAA7114H for analog of NTSC video image decode. And under FPGA's logic controlling, effective digital video signal was transferred to S3C2440 for further treatment. Finally within the embedded Linux environment, we programmed the visual user interfaces using the QT/Embedded, realizing the offline record of the real-time video images of digestive tract portable and preferences. It can make patients move more freely and even without PC when examining. In addition, the method greatly improves the efficiency of the doctor, and is more intelligent and with more humane nature. PMID- 22097260 TI - [Fetal electrocardiogram extraction based on independent component analysis and quantum particle swarm optimizer algorithm]. AB - Fetal electrocardiogram (FECG) is an objective index of the activities of fetal cardiac electrophysiology. The acquired FECG is interfered by maternal electrocardiogram (MECG). How to extract the fetus ECG quickly and effectively has become an important research topic. During the non-invasive FECG extraction algorithms, independent component analysis(ICA) algorithm is considered as the best method, but the existing algorithms of obtaining the decomposition of the convergence properties of the matrix do not work effectively. Quantum particle swarm optimization (QPSO) is an intelligent optimization algorithm converging in the global. In order to extract the FECG signal effectively and quickly, we propose a method combining ICA and QPSO. The results show that this approach can extract the useful signal more clearly and accurately than other non-invasive methods. PMID- 22097261 TI - [A novel voltage multiplier for X-ray power supply]. AB - In this paper, a seriesly connected three phase bipolar symmetrical voltage multiplier (VM) is proposed, which is a novel VM for X-ray power supply. It consists of three single phase bipolar symmetrical VM, which are connected in series at their smoothing columns. The charging and discharging process occurs six times in a cycle and the frequency of the output voltage ripple is six times as large as the drive signal frequency. The proposed VM has three times larger output voltage and three times smaller ripple factor as compared to single phase bipolar symmetrical VM, and smaller voltage drop and faster dynamic response than those of the series connected three phase symmetrical VM. The simulation is provided to show the feasibility of proposed VM. PMID- 22097262 TI - [Improved mechanical strength and cell occlusivity of electrospun L-polylactic acid aligned nanofibrous membranes by post heat treatment]. AB - Electrospun nanofibrous materials are considered as ideal scaffolds for tissue engineering because their fibrous structure is quite similar to the morphology of natural extracellular matrix, and they can offer biomimetic microenvironment for cell growth. However, the highly porous scaffolds are too weak to meet the mechanical requirement of guided tissue regeneration (GTR). In the present investigation, electrospun L-polylactic acid (PLLA) nanofibrous membranes were collected with high speed rolling method, and then hot stretched and annealed to improve the tensile strength and cell occlusivity. The membrane with the maximum tensile strength (strength 103MPa and modulus 1.83GPa) was obtained by hot stretching for twice at 100 degrees C and further annealed for 10min at the same temperature. Cytotoxicity test showed that the heat treated membrane supported well the attachment and growth of human periodontal ligament cells, but inhibited the cell proliferation. The cell occlusivity of the membrane was also significantly improved as the porosity decreased after heat treatment. It could be used as the enhancement interlayer of barrier materials for GTR. PMID- 22097263 TI - [Contributions of edentulous mandibular alveolar ridge height and denture adhesive to complete denture retention]. AB - The present paper is to investigate the relationship between height and stress bearing area of mandibular alveolar ridge, their influence on retention of complete denture, and the effectiveness of denture adhesive (DA). Five mandibular edentulous models of different heights and a rabbit palate model were prepared in Die-Stone. Measurements were made on the heights and stress-bearing areas of mandibular alveolar ridge, the retention force of mandibular models 15 min after DA administration, and the retention force on the rabbit palate before and after adhering. All available data were analyzed statistically. Linear regression relationship was demonstrated between ridge height and bearing area, ridge height and retention force, and bearing area and retention force (P<0.01), separately. Retention force per unit area was positively related to the height and area. Retention force increased to 2.87 times postadhesive-treating. Height and stress bearing area of mandibular alveolar ridge directly correlate with the retention of complete denture, and DA significantly improves the retention ability of complete denture. PMID- 22097264 TI - [Design & fabrication of porous core implant with preset channel network for osteonecrosis of the femoral head]. AB - Referring to the anatomical characterization of natural spongy bone and channel network in cortical bone, we designed a new pattern of biomimetic impalnt with preset channel for blood vessel inserting to treat early femoral head necrosis. The surgical ptrocedure was simulated by CAD model. Ceramic stereolithography was applied to fabricate the green part. Other process, such as dehydration, rinsing, drying and sintering, were taken successively. The final ceramic part kept identical with the engineered part either in the shape or in the internal structure. No deformation or crack happened. Pore size, interconnected pore size, porosity and interconnected porosity of ceramic part could satisfy cellular grouth. Spectrum analysis showed that no phase transition or chemical reaction happened during fabrication process. The biocompatibility of the final part kept the same with original during beta-TCP powder. The compressive strength was 23.54 MPa, close to natural spongy bone. It is an ideal implant to treat early femoral head necroseis because it makes preimplantation of cells and biological factors, blood velssel inserting, early establishment of blood supply possible. At the same time, it could provide enough mechanical support to prevent collapse of femoral head. It could provide a wide clinical foreground. PMID- 22097265 TI - [Study of blood compatibility on TiO2 coated biomedical Ni-Ti shape memory alloy]. AB - We coated a thin TiO2 film on the surface of Ni-Ti shape memory alloy by activated sputter method in the present work. The blood platelet adherence and antithrombogenicity of the TiO2-coated Ni-Ti alloy were evaluated. The results showed that the platelets on the TiO2-coated Ni-Ti alloy were fewer than those on 316L stainless steel, and no agglomeration or distortion for the platelets on the coated alloy was found, which means less probability of blood coagulation for the alloy. The coagulation time on the coated Ni-Ti shape memory alloy was longer than that on the 316L. Compared with that on the 316L stainless steel, the TiO2 coated Ni-Ti shape memory alloy showed better blood compatibility, indicating that the Ni-Ti alloy with TiO2 coating is a kind of ideal biomedical materials with high clinical value. PMID- 22097266 TI - [Construction of Sirtl shRNA interfering vector and its effects on cell proliferation and apoptosis]. AB - This study was aimed to construct Sirt1 shRNA interfering vector and to analyze the effects of Sirtl on cell proliferation and apoptosis in HepG2, A549 and 293T cell lines. To design and synthisize Sirtl shRNA sequence then recombinate it to pGenesil-1.0 plasmid, the positive pGenesil-1.0-Sirtl vector clone was screened by effective detections and sequencing. The vectors were transfected into HepG2, A549, 293T cell lines, and Sirtl expression levels in these clones were detected by RT-PCR and Western-blot. These clone cell proliferation activities were detected by MTT, and these cells apoptosis incidences were detected by MTT experiment after treated with DOX. The results showed that Sirt1 shRNA interfering vectors were successfully screened. The levels of Sirtl expression in HepG2-sh, A549-sh and 293T-sh cells were significantly reduced compared with their control cells. It was indicated that the proliferation activities of these cells were impaired and anti-apoptosis capabilities of HepG2-sh, A549-sh and 293T sh were also impaired notably. Sirt1 took an important role in maintaining cell proliferation and resisting cell apoptosis caused by DNA damage, and this result also provided theoretical information for the further research. PMID- 22097267 TI - [Construction of NK4 gene lentiviral vector and its expression in bone mesenchymal stem cells]. AB - The present investigation was to construct lentiviral vector carrying the human gene NK4 and transfect the human bone mesenchymal stem cells (hBMSCs) and to determine the expression of NK4 gene in hBMSCs after transfection. The NK4 gene was obtained from HGF cDNA by polymerase chain reaction(PCR), and the pGC-FU-NK4 plasmid was constructed by double restriction enzyme digestion and gene recombinant. The titer of virus was tested by real-time quantitative PCR. After transfected by lentivirus, the green fluorescent protein (GFP) in hBMSCs was observed using fluorescence microscope, and the expression of NK4 in culture supernatant was detected by enzymelinked immunosorbent assay (ELISA). The sequence of the PCR product was consistent with the data of GeneBank by DNA sequencing. The virus titer was 2 X 10(8)TU/ml. Strong green fluorescence was observed in the cell membrane and cytoplasm of hBMSCs with fluorescent microscopy. The expression of NK4 in culture supernatant was increased with time extension. The hBMSCs can be transfected by NK4 gene expressing lentiviral vector safely and effectively, and the expressin and secretion of NK4 was persistent and stable. PMID- 22097268 TI - [Preliminary research of induction of the multiple HPV antibody by HPV L1 type conserved sequence aimed at human papillomavirus major protein]. AB - To investigate whether a conserved sequence of the human papillomavirus(HPV) L1 protein consisted of 12 amino acid residue can induce the antibody aimed at multiple HPV types, we screened a conserved sequence of the HPV L1 protein by forecasting B cell epitope and comparing multiple sequences. The peptide was synthesized, mixed with Freund adjuvant, and used to immunize rabbits, and those in the control group were only immunized with Freund adjuvant. Then the antibody titer was identified by indirect enzyme-linked immunosorbent assay (ELISA). And immunocytochemistry, immunofluorescence, western blot and immunohistochemistry were used to detect whether the antibody could react with cervical cancer cell lines and cervical tissue that had been identified with HPV infections. We found that the antibody titer was greater than 1:25600. Moreover, we confirmed that the antibody could react with cervical cancer cell lines and cervical tissue with HPV infections. The results showed that the peptide could induce antibody aimed at multiple HPV types. Our findings have great significance in further research of the broad spectrum HPV, HPV L1 diagnosis kits. PMID- 22097269 TI - [Application of orthogonal analysis to the optimization of HPV16 E2 protein expression]. AB - This study was aimed to identify pET21b-HPV16E2/BL21(DE3) strain and to optimize the expression of human papillomavirus type 16 (HPV16) E2 protein by orthogonal analysis. Four influence factors on two levels were selected to increase the target protein quantity. The four factors were induction time, induction temperature, inductor concentration and cell density. The quantity of HPV16 E2 protein was used as the evaluation parameter. Induced by IPTG, HPV16 E2 protein was analyzed by SDS-PAGE and Western Blot. Target protein was analyzed by GIS imaging system to quantify the protein level. SPSS13. 0 software was applied to analyze the result. Data showed that the expression strain pET211rHPV16 E2/BL21(DE3) was identified correctly. HPV16 E2 protein expressed mainly at insoluble form. The 42KD protein band was identified by SDS-PAGE and Western blot. Orthogonal test was applied on influence factor analysis and expression optimization successfully. Main influence factors were inductor concentration and induction temperature. The optimimum condition of maximum expression quantity was 37 degrees C, 7h, 1.0 mmol/L IPTG and OD600 1.0. In this experiment, orthogonal test could not only be used to analyze the influential factors and promote the target protein expression, but also be used to provide a better experiment method for molecular biological study. PMID- 22097270 TI - [The effect of NK-1 tachykinin receptor antagonist on hypoxia induced hepatic function injury and hepatocellular apoptosis in rats]. AB - To investigate the effect and mechanism of NK-1 Tachykinin receptor (NK-IR) antagonist on hypoxia induced hepatic injury, we established the hypoxic rat model. 30 male SD rats (weighing 240-300g) were randomly divided into 3 groups, control group, and experimental groups including the hypoxia group and the NK-1R antagonist group. The rats of experimental groups underwent hypoxia, among them the NK-1R antagonist group were those with interference of NK-1R antagonist by intraperitoneal injection. Hepatic injury was evaluated by pathological staining, hepatic function detection and hepatocellular apoptosis determination. Results showed hypoxia-induced hepatic injury in rats was established successfully. Edema,ballooning degeneration and spotty necrosis were found in livers in the experimental groups, among which the pathological injury in the hypoxia group was worse than that in the NK-1R antagonist group. Moreover,GGT and the rate of hepatocellular apoptosis in the NK-1R antagonist group were obviously lower than that in the hypoxia group (P<0.05). But no significant difference were found in ALT,AST and ALP between groups (P>0.05). These data indicate that Substance P possibly participate in the process of hypoxia-induced hepatic injury, and NK-1R antagonist could reduce hypoxia-induced hepatic injury. PMID- 22097271 TI - [20-year search on molecular markers of Leishmania isolates from different Kala azar foci in China to confirm whether genetic fingerprints of Kala-azar pathogens correlate with disease types]. AB - Leishmaniasis (Kala-azar) from different endemic regions of China expresses different clinic and epidemiological features, and traditionally is classified as hilly, plain and desert types/foci. We concentrated our review on whether the pathogens from those foci were different at molecular level, if so, whether there are were molecular markers readily identifiable by molecular technologies. This was a review of a 20-year search for such markers by using kinetoplastic DNA (kDNA), nDNA hybridization, PCR-SSCP, RAPD and sequence analysis of SSU rDNA variable regions and LACK gene. The results showed that heterogeneities at molecular level exist in Leishmania isolated from different foci of China, which could be used as markers for different types of Leishmaniasis in China. PMID- 22097272 TI - [A segmentation algorithm of OCT image for macula edema]. AB - According to the characteristics of OCT images for macula edema, we studied a method for segmentation of the macula edema. Based on the Chan-Vese model, we proposed an improved level-set algorithm. With defining the integer-valued signed function directly, the curve could evolute outward or inward by changing the inside neighboring rid points and outside neighboring grid points into each other. We realized image segmentation which is much faster than the method of Chan-Vese model and smoothness regularization. We segmented 45 images and extracted the macula edema of each image. After achieving good segmentation results, we estimated the volume of the macular edema. The method provides quantitative analytic tools for clinical diagnosis and therapy. PMID- 22097273 TI - [Simulation of extracellular action potential for hippocampal pyramidal neurons]. AB - In order to extract more information from extracellular action potential (EAP) of neurons recorded deep in the brain tissue, we established simulation models of various pyramidal neurons in the hippocampal CA1 region and investigated the effects of dendrite currents, cell morphology and ion mechanisms on the formation of EAP waveforms. The results show that dendrite currents have significant effects on the EAP at the locations far from cell body, but not on those near cell body. The differences of shape of various pyramidal neurons result in large changes in the EAP amplitudes. However, the shapes of these different EAP are very similar. Ion mechanisms, such as calcium channels, have little effect on EAP waveforms. These results provide important information for experimental EAP recordings, EAP data analysis, and developing new methods to extract more neuronal data from EAP. PMID- 22097274 TI - [Expression of C-fos, C-jun in hippocampus under the model of transmitting epileptic discharge from brain tissue to muscular tissue on its own skull]. AB - The objective of this study was to investigate the changes of the behaviors, EEG and expression of c-fos, c-jun on induced seizure in rats by injecting penicillin after transmitting epileptic discharge from brain tissue to muscular tissue on skull. Eighteen experimental rats were divided into 3 groups, with each 6 rats. Seizure group: 6 acute seizure models were established by injecting penicillin in hippocampus of rats; Transferring group, 6 acute seizure models were established by injecting penicillin in hippocampus of rats, and electrode connected to muscles was planted into epileptic focus of each rat; Control group, 6 rats were only planted electrode in hippocampus without injecting penicillin. Then we observed the changes of behaviors, EEG and expression of C-fos, C-jun in hippocampus with immunohistochemical method. There was no statistic difference in seizure frequency of rat between seizure group and transferring group, but the discharging frequency in EEG of transferring group lowered significantly (P<0.05). The expression of C-fos, C-jun in hippocampus of transferring group rats was significantly lower than that of seizure group (P<0.005). It could be concluded that under the model of transmitting epileptic discharge from brain tissue to muscular tissue on skull, the burst times on EEG electrode decreased, concomitantly with the lower expression of C-fos, C-jun in hippocampus. PMID- 22097275 TI - [Application of pulse-coupled neural network combined with genetic algorithm on MR images of hypoxic-ischemic encephalopathy]. AB - This paper is to provide a basis for the establishment of an early diagnostic system for hypoxic-ischemic encephalopathy (HIE) by performing segmentation and feature extraction of lesions on the MR images of neonatal babies with HIE. The segmentation on MR images of HIE based on the genetic algorithm (GA) combined with a pulse-coupled neural network (PCNN) were carried out. There were better segmentation results by using PCNN segmentation based on GA than PCNN segmentation with fixed parameters. The data suggested that a PCNN based on GA could provide effective assistance for diagnosis and research. PMID- 22097276 TI - [Study on visual display terminal mental fatigue status based on physiological information]. AB - A visual display terminal (VDT) mental fatigue task was designed to search for the objective indicator to diagnose and evaluate the VDT mental fatigue status. The signals of temperature and electrocardiograph (ECG) are collected from the subjects. The temperature, heart rate (HR) and heart rate variability (HRV) are extracted as the objective parameters after analyzing the temperature signals in time domain and the ECG signals in time domain and frequency domain. Compared with mental fatigue pre-experiment, the temperature increased significantly (P<0.001), and the RR-PNN50 increased obviously (P<0.05), while the S wavelet of ECG signals decreased obviously (P<0.05) after mental fatigue experiment. Compared with the end of mental fatigue experiment, the temperature increased, the changes of RR-PNN50 were not obvious, the S wavelet increased significantly (P<0.01), and the mental fatigue was somewhat remittance after natural recovery. The results showed that the objective indicator to evaluate the VDT mental fatigue status would be hopeful to be found out by analyzing the signals of temperature and ECG. PMID- 22097277 TI - [Design of a three-dimensionally controlled multi-cell-assembly system based on the control of a mixer nozzle]. AB - Three-dimensionally controlled cell-assembly technique makes fabricating tissues and organs in vitro to be possible. However, for real tissues and organs with complex structure and various cells, fabricating tissues and organs in vitro need a technique that could assemble and locate multi cells and materials precisely in the space. Facing the needs of multi-cell assembly, we designed a mixer nozzle and the matching pulse switching circuit which based on the single-nozzle cell assembly system, and developed a multi-cell-assembly system. We also carried out some assembly experiments with this system using materials that were similar to the multi-component extracellular matrix materials. The results demonstrated that the system could assemble various cells and materials into three-dimensional inhomogeneous structures precisely. PMID- 22097278 TI - [A review of research progress on biological effects about nanometer scaffold for bone tissue engineering]. AB - Quite a few orthopedics experts have fabricated some novel bone scaffolds with nanotechnology and have carried out some researches on nano-biological effects. The study of the biological effects about nano-biomaterials can facilitate the understanding of the interaction between the biomaterials and the organism, and provide research ideas and direction to construct new biomaterials with physiological function. To better understand the interaction of nano biomaterials with protein, cells and bio-security, this review presents recent advances of biological effects about nano scaffold for bone tissue engineering. PMID- 22097279 TI - [Research progress on key technology of power and signal transmission in neuroprosthetic]. AB - The power and signal transmission technology is one of the key technologies in neuroprosthetic research. This paper proposes firstly the related theory of power and signal transmission technology in neuroprosthetic, then summarizes the three key aspects of the power and signal transmission technology in neuroprosthetic. After analyzed the development of the inductive wireless power harvesting technology, the wireless telemetry technology and the wireless power harvesting telemetry technology, the emphasis on research contents will be proposed and discussed, which will help accelerate the further research of prosthetic. PMID- 22097280 TI - [Progress of research in retinal image registration]. AB - The retinal image registration has important applications in the processes of auxiliary diagnosis and treatment for a variety of diseases. The retinal image registration can be used to measure the disease process and the therapeutic effect. A variety of retinal image registration techniques have been studied extensively in recent years. However, there are still many problems existing and there are numerous research possibilities. Based on extensive investigation of existing literatures, the present paper analyzes the feature of retinal image and current challenges of retinal image registration, and reviews the transformation models of the retinal image registration technology and the main research algorithms in current retinal image registration, and analyzes the advantages and disadvantages of various types of algorithms. Some research challenges and future developing trends are also discussed. PMID- 22097281 TI - [Research on the aging of all-ceramics restoration materials]. AB - All-ceramic crowns and bridges have been widely used for dental restorations owing to their excellent functionality, aesthetics and biocompatibility. However, the premature clinical failure of all-ceramic crowns and bridges may easily occur when they are subjected to the complex environment of oral cavity. In the oral environment, all-ceramic materials are prone to aging. Aging can lead all-ceramic materials to change color, to lower bending strength, and to reduce anti-fracture toughness. There are many factors affecting the aging of the all-ceramic materials, for example, the grain size, the type of stabilizer, the residual stress and the water environment. In order to analyze the aging behavior, to optimize the design of all-ceramic crowns and bridges, and to evaluate the reliability and durability, we review in this paper recent research progress of aging behavior for all-ceramics restoration materials. PMID- 22097282 TI - [Research progresses on ergonomics assessment and measurement methods for push pull behavior]. AB - Pushing and pulling (P&P) is a common operating mode of operator's physical works, and plays an important role in evaluation of human behavior health and operation performance. At present, there are many research methods of P&P, and this article is a state-of-art review of the classification of P&P research methods, the various impact factors in P&P program, technical details of internal/external P&P force measurement and evaluation, the limitation of current research methods and the future developments in the ergonomics field. PMID- 22097283 TI - [The update progress of physical treatment for osteoporosis]. AB - Treatments for osteoporosis have many varieties, and the role, characteristics of them are also different. This paper investigates from the perspective of physical therapy pulsed electromagnetic fields (PEMFs), shock wave, and low-intensity pulsed ultrasound (LIPUS) therapy. Then comprehensive analysis of their mechanism of action, clinical application of new advances for more reasonable choice for clinical treatment and further trend of research are discussed. Through the research and discussions, we find out the strengths, weaknesses, and the best method of treatment in order to achieve better therapeutic effect. PMID- 22097284 TI - Methods of predicting visceral fat in Brazilian adults and older adults: a comparison between anthropometry and computerized tomography. AB - Visceral adipose tissue (VAT) is linked with the metabolic consequences of obesity, being necessary the use alternative methods of predicting this type of fat, like anthropometry. The objective of this study was assess the performance of anthropometry in predicting visceral fat measured with computerized tomography in adults and older adults. Study transversal with 197 individuals underwent computerized tomography (CT) and anthropometry. The variables analized were: visceral adipose tissue area by CT, Sagittal Abdominal Diameter (SAD), Waist Circumference (WC) and Waist-Hip Ratio (WHR). A descriptive analysis, Pearson correlation and ROC curve were carried out. We observed Correlations higher than 0.7 (p = 0.000) between the SAD, WC and the VAT area were found in adult men and older men and in adult women. WHR displayed the least correlations. The most sensitive and specific SAD cut-off points were equal for all the men (Adults: 20.2 cm/Older adults: 20.2 cm) but different for the women (Adults: 21.0 cm; sens.: 83.3; spec.: 79.1/Older adults: 19.9 cm; sens.: 81.0; spec.:79.3). The WC cutoff points that identified a VAT area = 130 cm2 were 90.2 cm and 92.2 cm for men (adult men--sens.: 86.7; spec.: 86.1--and older men-sens.: 79.3; spec.: 77.8 respectively), while for women the recorded values were 92.3 cm (adult women- sens.: 83.3; spec: 81.4) and 88.2 cm (older women--sens.:76.2; spec.: 69.0). This study showed that WC and SAD achieved the best performance in the identification of visceral fat considered at risk for the development of cardiometabolic diseases in adults and older adults. PMID- 22097285 TI - [Impacts of technological knowledge of small indigenous farmers on food availability in the Mexican southeast]. AB - This study was conducted to evaluate the impact of technological knowledge (acquired in Farmer Field Schools) on the availability of food for poor indigenous farmers, who are mainly dedicated to the production of maize for home consumption in the Cuicateca regi6n, Oaxaca, Mexico. The variables analyzed were 1) Level of technological knowledge, 2) maize yield, and 3) time that the last maize harvest supplied the food needs of the farmers in question (a proxy indicator of food availability). A random sample of 36 participants in the rural training schools and a control group of the same size were given questionnaires at the beginning and end of their study. The statistical analysis was done using the Pearson chi-2 contrast test and the Kolmogorov-Smirnov test. After finding that there was no normal distribution, the Wilcoxon test to contrast paired data was used, and finally, correlations were obtained. It was found that the increase in technological knowledge of 7.29 +/- 1.01 to 46.64 +/- 18.40 did not correlate (P > or = 0.05) with the time that the last maize harvest lasted in providing food. The results show that the increase in technological knowledge does not increase availability of maize as food. PMID- 22097286 TI - [Odds ratio between sociocultural factors, body dissatisfaction, and body mass index in university students of Hidalgo, Mexico]. AB - After to identify risky factors involved in the prediction and prevention of eating disorders (ED), in a sample of university males and females students from an urban setting in Hidalgo. Mexico; the main purpose of this paper was to reaffirm the following assumptions: 1) Dissatisfaction with body shape is closely related to both, the influence of sociocultural factors as Body Mass Index (BMI); 2) The participating women reported more dissatisfaction with body shape, indicating greater influence of sociocultural factors than men.Transversal, descriptive and association field research was carried out in a sample of 490 students (57% females. 43% males), from 16 to 30 years old (X(-) = 19.63, SD = +/ 2.11). Multidimensional self-reported questionnaire were applied. BMI was obtained by measuring each subject's weight and height. Regarding the impact association measures obtained by Odds Ratio, there were significant association (p < 0.05) between high BMI and body image dissatisfaction. Also, statistically significant associations (p < 0.05) were found between body dissatisfaction and sociocultural factors (distress because of body image, influence of advertising, and influence of verbal messages), and between BMI and these latter, where men showed a higher risk. Findings suggest that body dissatisfaction in women, and BMI, specifically overweight in men, act like key agents of the impact of sociocultural factors in the researched sample. PMID- 22097287 TI - [Quality of the diet of women with severe and morbid obesity undergoing gastric bypass and sleeve gastrectomy]. AB - The objective of this study was to evaluate the changes of dietary intake and quality of the diet in patients undergoing gastric bypass and sleeve surgery. In 36 women with severe and morbid obesity it was assessed their nutrient intakes and dietary quality before and 6 months after bariatric surgery through three-day food records. Vitamin and mineral intakes from supplements were strictly controlled. Energy and nutrient intakes were significantly decreased 6 months after surgery bypass compared to the pre-surgery period with the exceptions of calcium and vitamin C. No differences were observed between groups. The Dietary quality index was also similar in both groups. Dietary intakes of calcium, iron, zinc, copper, folic acid, vitamin C, and vitamin E were below 100% of adequacy from at the 6th month after the surgery. Nevertheless, by considering both diet and supplements supply, nutrient adequacy of all but calcium and folic acid was above 100% in both groups. Gastric bypass patients presented greater values. In conclusion, these patients present an important reduction of their energy and nutrient intakes, with no major impact of the type of surgery. Supplement characteristics are crucial to cover nutritional needs. PMID- 22097288 TI - [Comparative analysis of growth and sexual maturation in girls of Santa Rosa (La Pampa) and La Plata (Buenos Aires), Argentina]. AB - The aim of this study was to analyze growth in relation to menarche in girls from two Argentinean urban populations. We performed a comparative-descriptive cross sectional study in 2474 schoolchildren between 8.0 and 16.9 years old from Santa Rosa (SR) and La Plata (LP) cities. We registered the presence of menarche and anthropometrics variables of body weight, total and sitting heights, arm circumference, triceps and subscapular skinfolds. Body mass index, subscapular/triceps index and muscle and fat arm areas were calculated. The study group was divided into 4 groups according to the city and menarche. The socio environmental structured survey indicated significant differences between cities with these variables: tenure status, building materials and services, health care coverage, cash assistance, educational level and parents' occupation, therefore establishing a higher welfare in youngsters of SR. Menarche at a mean age of 12.7 years old was more prevalent in SR (40.6%) than in LP (33.7%) (c2 = 12.9; p < 0.01). The ANOVA indicated significant differences between cities in total and sitting heights and muscle area (p < 0.01), body weight and arm circumference (p < 0.05) which were generally held in the post hoc comparison by age in pre menarche and post-menarche groups. The presence of a small body size at the expense of lowering in: total height, muscle area and leg length in LP youngsters, associated with a lower prevalence of menarche in this city, it would represents the adaptive cost of a lower welfare environment. PMID- 22097289 TI - [What kind of intervention has the best results to reduce the weight in overweighted or obese adults?]. AB - Evidence has shown that interventions which involve changes in a person's lifestyle, such as diet and physical activity, lead to weight loss and thus reduce the risk factors of cardiovascular disease. However, the effectiveness and necessary duration of specific interventions are unclear. The purpose of this research was to evaluate and compare the effect on weight of interventions based on diet, exercise and a combination of both. The research subjects were overweight and obese adults, at six and twelve months after the beginning of the intervention. First a systematic review was carried out, followed by a meta analysis. Initially, 24 studies were selected which met the established criteria for inclusion; twelve of these demonstrated the required level of quality. The diet-based interventions resulted in reductions of-6.66 kilograms (95% confidence interval (CI): -9.04 to -4.28) and -3.80 kilograms (CI: -5.50 to -2.10) at six and twelve months, respectively. Those who engaged in exercise showed a loss of 2.21 kilograms (CI: -4.62 to -0.21) and -2.00 kilograms (CI: -5.70 to -1.70) at six and twelve months, respectively, while those who changed their diets and engaged in exercise showed a loss of -10.86 kilograms (CI: -13.22 to -8.49) and 6.50 kilograms (CI: -8.09 to -4.90) at six and twelve months. The combination of diet and exercise showed the best effect in reducing weight among overweight and obese people, followed by diet alone while exercise alone didn't reach significant results. The effect of these interventions was greater during the first six months of intervention. PMID- 22097290 TI - [Metabolic parameters and risk factors associated with abdominal obesity among female adolescents in public schools in the Distrito Federal (Brazil)]. AB - This study aimed to estimate the prevalence of abdominal obesity and investigate their association with parameters markers of metabolic syndrome (MS) and its risk factors in female adolescents. It is a cross-sectional study with 150 adolescents from 10 public schools in the Federal District, Brazil. The presence of abdominal obesity was considered by measuring waist circumference above the 80th percentile, according to Taylor et al. (2000). The associated factors included sociodemographic characteristics, health status of adolescents and their parents, physical activity, eating habits, blood pressure and biochemical profile. The abdominal obesity prevalence ratio (PR) was estimated by Poisson regression model, with 95% CI. Among the adolescents studied (age= 15.6 +/- 0.8 years; BMI = 21.0 +/- 3.0 kg/m2), prevalence of abdominal obesity was 20%, and this condition was not associated with sociodemographic variables, physical activity and diet. However, abdominal obesity was significantly associated with intake of less than 4 meals a day (PR = 2.27; IC95% 1.27-4.10), previous obesity (PR = 2.36; IC95% 1.31-4.01), history of parental chronic disease (PR = 3.55; IC 95% 1.63-7.75), fasting insulin = 15 uUi/mL (PR = 3.05; IC 95% 1.36-6.82) e HDL-c > 40 mg/dL (PR = 0.39; IC95% 0.23-0.67). In this population, modifiable factors, family history and determinants of MS, such as insulin and HDL-c were associated with abdominal obesity, which points to the need for effective health promotion among adolescents. PMID- 22097291 TI - Identification of Lactobacillus spp. in colostrum from Chilean mothers. AB - The biodiversity of Lactobacillus spp. in colostrum samples from 116 Chilean mothers was analyzed by PCR and 16S rDNA sequencing. Lactobacilli were isolated in 55.3% of the samples, with concentrations of 3.33 +/- 0.55 (log CFU/ml). The predominant species were L. plantarum (64%), L. fermentum (16%) and L. pentosus (9%). 28% of the isolated strains were resistant to gastric pH and bile salts, suggesting that they could be used as probiotics. PMID- 22097292 TI - [Bacteriological quality of traditional, organic and hydroponic cultured lettuce in Costa Rica]. AB - The main objective of this work was to evaluate the microbiological quality of lettuces commercialized in the Metropolitan Area of San Jose, Costa Rica, and cultured in different ways, in order to detect differences between the culturing methods and the risk that these products may represent for Public Health. The study was done at the Food Microbiology Laboratory, Universidad de Costa Rica, from March to July, 2010. 30 lettuce samples were analyzed (10 obtained by traditional culture, 10 by organic culture and 10 by hydropony). All samples were obtained from markets where their origin was certified. Total aerobic plate count, total and fecal coliforms count and Escherichia coli were determined to all samples, as well as the presence/abscense of Salmonella spp. and Listeria monocytogenes in 25 g. Results obtained show that there is no statistically significant difference (p < 0.001) between the different types of cultures analyzed for any of the parameters evaluated. An important percentage of the samples presented coliforms, nevertheless, just one E. coli strain was isolated from a traditionally cultured lettuce sample. Four different Salmonella spp. strains were isolated from the samples as well as one Listeria monocytogenes strain. Data obtained show that the consumption of this product, raw or without an adequate hygiene and disinfection may represent a risk for health. Also, from the bacteriological point of view, there is no significant difference between the culturing methods evaluated, suggesting that the specific directions for each type of culture are not followed or that there is an inadequate handling of the products or post harvest contamination. PMID- 22097293 TI - Impact of solar dehydration on composition and antioxidant properties of acai (Euterpe oleracea Mart.). AB - Commercial products derived from the acai fruit (Euterpe oleracea Mart.) are available in Brazil, but in Venezuela, it is only known by ethnic indigenous groups of the Amazon. In this study, acai flour was made by solar dehydration and the effect of processing on the composition, microbiological quality, and antioxidant properties of such flour were evaluated. The fruit was purchased in Puerto Ayacucho, Venezuela, and a portion was manually pulped. Microbiological quality, proximal composition, minerals, polyphenols, tannins, anthocyanins, and antioxidant capacity were evaluated. The remaining portion of fruit was blanched in a solution of ascorbic acid and citric acid at 98 degrees C for 1 min in the same manner, manually pulped, dried by solar dehydration and the acai flour was also analysed. From the composition of the acai flour, its high content of fat (22.9%), protein (13.7%), dietary fibre (20.5%), total polyphenols (1.60 g/kg) and antioxidant capacity (79.97%) stood out. The blanching of the fruit and the solar dehydrating of the acai pulp did not modify the composition, but they improved its microbiological quality and reduced phenolic compounds and antioxidant capacity. The flour obtained is stable and innocuous and could be used to diversify the diet of the indigenous people of the Amazon region. PMID- 22097294 TI - [Mineral bioaccessibility in yerba mate (Ilex paraguariensis St) infusions and mixtures with iron fortified milk]. AB - The bioaccesibility of various minerals in infusions of yerba male (mate cocido) and preparations with Fe-fortified milk was assessed to determine the influence of the infusions on the potential bioavailability of intrinsic minerals and fortified Fe. The dialyzability (D) of iron, calcium, magnesium and zinc was evaluated, as indicator of bioaccesibility in milk samples fortified with ferrous sulfate (FS), ferric bisglicinate GF) and EDTANaFe. Dialyzability was also evaluated in mixtures of milk with mate cocido and in infusions cooked with Fe fortified milk. In each case the effect of ascorbic acid (AA) in a ratio Fe: AA 1:4 was studied. In the mate cocido FeD was zero and increased to 15% with the addition of AA. The FeD in milk with SF, BGF and EDTANaFe (1.2, 1.0 and 27.4 respectively), increased with the addition of AA to 2.9, 3.5 and 24.8. The FeD in the mixture milk: mate cocido was 4.7%, 5.7% and 31.2% for SF, BGF and EDTANaFe respectively. With the addition of AA was 13.5%, 13.7% and 25.7%. In infusions cooked with SF fortified milk, the values were lower than those of the mixture. The CaD did not show significant changes in Fe fortified milk and its preparations with yerba mate, while the MgD and ZnD only showed a significant reduction in infusion cooked with Fe-fortified milk. The use of infusions of yerba mate does not provide significant amounts of minerals. However, its use in mixtures with milk will not adversely affect the availability of Fe in that matrix. PMID- 22097295 TI - [Basal state of the nutritional information declared in labels of foods products marketed in Costa Rica]. AB - The nutritional labeling regulations for prepackaged foods based on the Codex Alimentarius legislation enacted in 2002 in Costa Rica. In the same year, a research was conducted in order to describe the baseline of nutritional labeling. The declared information on the labels of all prepackaged foods was collected, except for alcoholic beverages. Six variables were analyzed using SPSS. 2,910 labels of foods were reviewed and classified in 19 food categories. 58.4% (n = 1698) included nutritional information, proportion that varied by country of origin and food category. Of the labels that included nutritional information, 68.1% had nutritional panel, 1.2% nutrient claims and 27.4%, both. 95% of the nutritional components declared on the labels included energy and macronutrients data. At least 100 different nutritional and health claims were identified. Most frequently used claims were content (74.7%), followed by addition (16.9%). The components most frequently mentioned were vitamins and minerals, vitamins (alone), carbohydrates, total fat, cholesterol and energy. Food groups who reported these descriptors were: cereals and by products, baby foods, milks, beverages, foods for special dietary uses and substitutes. One to five descriptors were used in a label. In a decade the proportion of prepackaged foods with nutritional labeling tripled in the metropolitan area of Costa Rica. It is concluded that the tendency of nutrition information declaration is up, sustained and represents an accessible tool for health promotion, if the information provided is reliable and secure. PMID- 22097296 TI - [Proximal composition, lipid and cholesterol content of meat from pigs fed peach palm meal (Bactris gasipaes Kunth) and synthetic lysine]. AB - Two experiments were conducted to evaluate the proximal composition, lipids and cholesterol content of meat from pigs fed diets with peach-palm meal (PPM), with or without addition of synthetic lysine (LYS). In experiment 1, 24 pigs were randomly allotted into six treatments with three levels of PPM (0.16 and 32%) and two levels of LYS (0 and 0.27%). In experiment II, 16 finishing pigs were fed with two levels of PPM (0 and 17.50%) and two levels of LYS (0 and 0.27%). At the end of each experiment (42 and 35 d, respectively), pigs were slaughtered and loin samples were obtained to determine crude protein, dry matter, moisture, ash, total lipids, and cholesterol content. In experiment I, pork loin from 16% PPM had more dry matter (26.45 g/100 g) and less moisture (73.49 g/100g) than pork loin from 32% PPM (25.11 y 75.03 g/100g, respectively). Meat samples from pigs without LYS had higher (p < 0.05) content of lipids (2.11 g/100 g) than meat from pigs that consumed LYS (1.72 g/100 g). In experiment II, the proximal, lipids and cholesterol content were similar among treatments. The PPM addition to pig diets did not affect the proximal composition of pork, while LYS addition indicated a reduction of total lipids, which could result as an alternative to obtain leaner meat. PMID- 22097297 TI - [The therapeutic strategy for burn wounds]. AB - Wound repair is the critical issue in burn injury management. Optimal coverage or regeneration of skin tissue is still a great challenge. In this review, we summarize the current achievements in the fields of immune tolerance induction, skin tissue regeneration, and hypertrophic scar control, which might provide new viewpoints and research direction for diagnosis and treatment of burn wounds. PMID- 22097298 TI - [Construction and operation of the wound care technology platform]. AB - Chronic wounds are a major healthcare problem costing billions of dollars a year over the world. However, it is regrettable that a large number of chronic wounds are still treated simply by conventional dressing change in local clinics, lacking of definite diagnosis and personalized care. This situation results in a low wound healing rate, unsatisfied life quality of the patients, and higher medical cost for the prolonged promiscuous care. We should not only emphasize the importance of wound care in clinical practice, but also emphasize the importance of establishing wound care centers. With the experience of our practice in wound care center, the construction of wound care technology platform is strongly suggested. This platform could act as an education base to train more professional wound care doctors, nurses, and care workers, as well as resolve many technical difficulties involved in the treatment of many complicated chronic wounds. PMID- 22097299 TI - [Current situation of negative-pressure wound therapy]. AB - Negative-pressure wound therapy (NPWT) has been used to help wound healing since early 1970s, and it has been used increasingly for treating a wide variety of wounds since the early 1990s and started to popularize in China near the mid 1990s. This technique is different from conventional dressing change, as it controls local humidity, alleviates edema, and improves local circulation all by negative pressure. The method generally involves the application of a dressing on the wound surface, connecting the dressing to a vacuum pump through a tube, and then sealing the wound with adhesive films. Most of the clinicians in China believe that NPWT is helpful in accelerating wound healing, though as yet there is no strong evidence to support it. Therefore, it is necessary to conduct more research to further clarify the mechanism and therapeutic effect of NPWT. PMID- 22097300 TI - [Efficacy of vacuum sealing drainage in mice infected with Pseudomonas aeruginosa and its mechanism]. AB - OBJECTIVE: To observe the effect of vacuum sealing drainage (VSD) on the proliferation of Pseudomonas aeruginosa (PA) in infected wound, and to explore its possible mechanism. METHODS: Full-thickness skin wounds each with area of 1 cm x 1 cm were produced on the back of 40 C57 BL/6 mice, and then they were contaminated with wild type PA strains PAO1 marked with target gene of bacterial luciferase luxCDABE (PAO1-lux), they were dressed for 24 hours to reproduce PA infection model. Then mice were divided into experiment [E, with treatment of VSD (pressure value at -16.625 kPa)] and control (C, with treatment of conventional dressing change) groups according to the random number table, with 20 mice in each group. The fluorescence intensity of PAO1-lux and blood flow in wound was respectively measured by in vivo optical imaging system and laser Doppler perfusion imager before treatment and at post treatment hour (PTH) 24. The expression levels of IL-1beta and vascular endothelial growth factor (VEGF) mRNA in wound edge were determined by real-time fluorescence quantitative RT-PCR before treatment and at PTH 24. The specimens of wound edge tissue were collected for observation of pathological change at PTH 24. Data were processed with t test. RESULTS: There were no obvious difference in fluorescence intensity of PAO1 lux and blood flow in wound between E and C groups before treatment (with t value respectively 0.03, 0.50, P values all above 0.05). The fluorescence intensity of PAOl-lux and blood flow in wound in E group at PTH 24 [(2.69 +/- 0.75) photons x s(-1) x cm(-2) x sr(-1) and (96 +/- 9) PU] was respectively lower and higher than that inC group [(5.18 +/- 0.96) photons x s(-1) cm x (-2) x sr(-1) and (70 +/- 11) PU, with t value respectively 3.54, 3.13, P values all below 0.05]. The expression levels of IL-1beta and VEGF mRNA in both groups before treatment were similar (with t value respectively 0.19, 0.07, P values all above 0.05). The expression levels of IL-1beta and VEGF mRNA in E group at PTH 24 was respectively 4.72 +/- 0.37, 2.68 +/- 0.39, all markedly higher than those in C group (2.24 +/- 0.50, 1.22 +/- 0.13, with t value respectively 6.90, 6.12, P values all equal to 0.00). The number of inflammatory cell infiltrating the wound edge in E group at PTH 24 was increased by nearly 77% as compared with that in C group. CONCLUSIONS: Compared with conventional dressing change, VSD can reduce the amount of Pseudomonas aeruginosa in full-thickness skin defect wound at the early stage, it may be related with an increase in blood flow and number of inflammatory cells in wound tissue, promoting expression of IL-1beta and VEGF mRNA. PMID- 22097301 TI - [Vascularization of poly-lactic-co-glycolic acid knitted mesh/collagen-chitosan hybrid scaffold]. AB - OBJECTIVE: To investigate the effects of poly-lactic-co-glycolic acid (PLGA) knitted mesh/collagen-chitosan hybrid scaffold (PCCS) on angiogenesis, and to explore the relative mechanisms. METHODS: PLGA knitted mesh was integrated into collagen-chitosan scaffold (CCS) to construct PCCS with freeze-lyophilizing method, and CCS was made with the same method. The characteristics of morphology and water absorbing capacity among PCCS, PLGA knitted mesh, and CCS were compared in vitro. PCCS and CCS was respectively implanted into subcutaneous tissue of back on both sides in 24 SD rats, and the tissue specimens were harvested at post operation week (POW) 1, 2, and 4 according to the random number table to evaluate the level of angiogenesis by histopathological and immunohistochemical examinations. The expression levels of alpha smooth muscle actin (alpha-SMA) and vascular endothelial growth factor (VEGF) mRNA were examined by real-time quantitative RT-PCR. Data were processed with t test. RESULTS: (1) PLGA knitted mesh was closely integrated with sponge of collagen-chitosan in PCCS, and the porous structure of PCCS was similar to that of CCS. (2) Compared with that of PCCS [(506 +/- 15)%], the water absorbing rate of CCS and PLGA knitted mesh was respectively increased and decreased [(627 +/- 21)%, (195 +/- 15)%, with t value respectively 3.8, 11.9, P < 0.05 or P < 0.001]. (3) The scaffolds were filled with newly formed tissue in CCS at POW 4, while those in PCCS were observed at POW 2 with more homogeneous and abundant collagen. (4) Blood vessels could be induced, and they grew into scaffolds along with prolongation of implantation time in PCCS and CCS. The number of mature blood vessels in PCCS at POW 1, 2, 4 [(10.7 +/- 3.2), (18.6 +/- 2.1), and (30.3 +/- 4.5) branches per square centimeter] was respectively higher than that in CCS [(5.4 +/- 0.9), (10.8 +/- 4.2), and (23.6 +/- 1.7) branches per square centimeter, with t value respectively 4.6, 4.4, 4.5, P values all below 0.01]. (5) The expression levels of alpha-SMA and VEGF mRNA in PCCS at POW 1, 2, 4 were significantly higher than those in the CCS (with t(alpha-SMA) value respectively 1.26, 1.63, 2.17, with t(VEGF) value respectively 5.52, 2.07, 1.78, P values all below 0.01). CONCLUSIONS: PCCS is able to induce the ingrowth of blood vessels rapidly and promote their maturity. The mechanical properties and microstructures of scaffolds play synergistic role in the process of angiogenesis. PMID- 22097302 TI - [Study on differentiation of human umbilical cord-derived mesenchymal stem cells into human sweat gland cells in vitro and the relative signal pathway]. AB - OBJECTIVE: To study the differentiation potential of human umbilical cord-derived mesenchymal stem cells (UCMSC) into human sweat gland cells (hSGC) and the role of extracellular signal-regulated kinase (ERK) pathway. METHODS: UCMSC and hSGC were isolated and cultured in vitro. The former was identified with expression of CD14, CD29, CD34, CD44, CD45, CD105, cytokeratin 7 (CK7), CK19, and carcinoembryonic antigen (CEA), while the latter was identified with expression of CK19 and CEA. UCMSC with density of 5 x 10(4) cells per well placed in lower compartment of Transwell chamber were divided into control group (C, cultured with nutrient solution without any stimulation), thermal injury group (TI, treated with heat-shocked hSGC with density of 1 x 10(4) cells per well inoculated into the upper compartment of Transwell chamber for indirect co culture), thermal injury + EGF group (TIE, treated with indirect co-culture as used in TI group, with addition of 50 ng/mL EGF), thermal injury + PD98059 group (TIP, treated with indirect co-culture as used in TI group, with addition of 10 nmol/mL ERK specific inhibitor PD98059) according to the random number table. One week after culture, the positive expression rates of CK7 and CK19 in UCMSC were detected by flow cytometry, the expression of CK19 and CEA in UCMSC were examined with immunohistochemical staining and the positive expression rate of CEA was calculated, and the expression level of phosphorylated ERK (pERK) was determined by Western blotting. Data were processed with one-way analysis of variance. RESULTS: (1) CD29, CD44, and CD105 were highly expressed in UCMSC, accompanied by low or negative expression of CD14, CD34, CD45, CK7, CK19, and CEA. The expression of CK19 and CEA were positive in hSGC. The two results showed that UCMSC and hSGC were pure. (2) Compared with those of C group [(2.2 +/- 1.5)%, (2.2 +/- 0.7)%, (3.3 +/- 0.7)%, 0.640 +/- 0.026], the expression levels of CK7, CK19, CEA, and pERK in UCSMC of TI group [(6.4 +/- 0.7)%, (5.7 +/- 0.3)%, (7.4 +/ 1.0)%, 0.790 +/- 0.049] and TIE group [(14.3 +/- 1.0)%, (12.6 +/- 1.1)%, (17.6 +/- 2.3)%, 1.200 +/- 0.032] were significantly increased (with F value respectively 78.49, 139.36, 87.13, and 191.74, P values all below 0.01), and those of TIE group were higher than those of TI group (with F value from 50.14 to 145.47, P values all below 0.01). There were no obvious difference in the 4 indexes between TIP group and C group (with F value from 0.00 to 0.13, P values all above 0.05). CONCLUSIONS: UCMSC co-cultured with heat-shocked hSGC can differentiate into hSGC, and ERK signal pathway participates in the process of differentiation of UCMSC into hSGC. PMID- 22097303 TI - [Preparation of polyvinyl alcohol/chitosan hybrid nanofibrous scaffolds and study on its biodegradation behaviors in vivo and in vitro]. AB - OBJECTIVE: To fabricate polyvinyl alcohol (PVA)/chitosan hybrid nanofibrous scaffolds owning the similar physiological structure of ECM, and to observe its biodegradation behavior in vivo and in vitro. METHODS: (1) The PVA nanofibrous scaffold and PVA/chitosan hybrid nanofibrous scaffold were fabricated by electrospinning technique, and then they were crosslinked by glutaraldehyde vapor method. The morphology of both scaffolds was observed by scanning electron microscope (SEM). (2) Biodegradation experiment in vitro: the samples of two scaffolds with size of 2 cm x 2 cm were placed into phosphate-buffer saline (PBS) fluid under 37.0 degrees C water for incubation, and then they were dried to observe morphologic changes under SEM on post incubation day (PID) 3, 7, and 14. (3) Biodegradation experiment in vivo: 48 Wistar rats were divided into PVA group and PVA/chitosan group according to the random number table, with 24 rats in each group. PVA or PVA/chitosan nanofibrous scaffold was implanted into subcutaneous tissue on both sides of back in rats of both groups, with 4 scaffolds in each rat. The scaffold samples were harvested to observe morphologic changes with HE staining on post operation day (POD) 3, 7, 14, and 28. RESULTS: (1) After crosslinking, the surface of fibers in PVA and PVA/chitosan hybrid nanofibrous scaffolds were smooth, and the diameters of fibers were similar, ranging from 200 to 300 nm, with high porosity. (2) Biodegradation experiment in vitro showed that the morphologic changes in fiber was respectively swelling, dissolution, fusion in PVA nanofibrous scaffold on PID 3, 7, 14, and that in PVA/chitosan hybrid nanofibrous scaffold was respectively swelling, dissolution and fragmentation, and disappearance. (3) Biodegradation experiment in vivo showed that the morphologic changes in scaffold structure was respectively loosening, fuzziness of edges, degradation, and disappearance in PVA group and PVA/chitosan group on POD 3, 7, 14, 28. CONCLUSIONS: PVA/chitosan hybrid nanofibrous scaffolds can be prepared with electrospinning technique, and it has an appropriate biodegradation rate compatible with tissue reconstruction after crosslinking. PMID- 22097304 TI - [Diagnosis and treatment of Kawasaki disease in burn children]. AB - We try to discuss the relationship between burn and Kawasaki disease (KD), and to study the diagnosis and treatment of KD in burn children. The medical records of one burn child with KD from our pediatric ward together with those of 5 burn children with KD retrieved from foreign literature were analyzed. The clinical features of KD, including bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, skin rash, cervical lymphadenopathy, changes in the distal part of extremities, were enrolled in the study. Six patients were male and younger than 5 years old, with 2 suffering from mild burn, 2 with moderate burn, and 2 with severe burn. Two days after second degree burn, all burn children had fever and skin rash with 4 or 5 clinical symptoms and signs of KD. Among them, coronary artery dilatation was found in 1 case as detected by echocardiography, positive wound culture was found in 2 cases, negative blood culture was found in 6 cases. All patients were given high-dose gamma globulin or (and) aspirin within 10 days after the first fever, followed by control and amelioration of the disease. We conclude that the pathogenesis of KD may be related with burn wound and reabsorption of edema. KD may be suspected in burn children younger than 5 years when they had fever and skin rash at the same time. PMID- 22097305 TI - [Comparison study of radionuclide lymphoscintigraphy and dynamic magnetic resonance lymphangiography for the diagnosis of extremity lymphedema]. AB - OBJECTIVE: To compare the role of radionuclide lymphoscintigraphy and dynamic magnetic resonance lymphangiography (MRL) for the diagnosis of extremity lymphedema. METHODS: Sixteen patients with primary extremity lymphedema and two with Klippel-Trenaunay syndrome combined with lymphedema were examined by lymphoscintigraphy using the tracer 99Tc-labelled dextran, and also by MRL using gadobenate dimeglumine as contrast agent. The results of morphological abnormalities and functional state of the lymphatic system at affected limbs from the two imaging methods were compared. RESULTS: Lymphatic vessels were imaged in 14 of 18 limbs with lymphedema using MRL, compared with one of 18 using lymphoscintigraphy. MRL detected the inguinal nodes in 16 of 17 patients, whereas lymphoscintigraphy revealed inguinal nodes in only nine cases. MRL revealed more precise information about structural and functional abnormalities of lymph vessels and nodes than lymphoscintigraphy by real-time measurement of lymph flow in vessels and nodes. CONCLUSIONS: Dynamic MRL is more sensitive and accurate than lymphoscintigraphy in the detection of anatomical and functional abnormalities in the lymphatic system in patients with extremity lymphedema. PMID- 22097306 TI - [Application of the cone beam computed tomography (CBCT) in Le Fort I osteotomy]. AB - OBJECTIVE: To improve the accuracy and safety of the Le Fort I osteotomy. METHODS: Eighty-four patients underwent CBCT scan before maxillary orthognathic surgery. The anatomic structures of maxilla were marked and measured. RESULTS: In 84 cases, there were 3 cases with severe hypoplasia of maxillary sinus, 11 cases with impacted third molar, 8 cases with separation in maxillary sinus, 4 cases with the deviation of nasal septum, and 3 cases with cysts in maxillary sinus. Form CBCT images, the position of the pterygopalatine canal, the thickness of maxillary wall, hidden lesion of maxillary sinus, the location of Impacted molar, the deviation of nasal septum, and other anatomic structure could be accurately localized. CBCT could provide sufficient and valuable information in diagnosis and design for Le Fort I osteotomy. CONCLUSIONS: CBCT imaging technology could provide precise anatomic images for Le Fort I osteotomy. It improves the accuracy and safety of the Le Fort I osteotomy. PMID- 22097307 TI - [Acellular cadaveric dermis-assisted immediate breast reconstruction: the preliminary experience]. AB - OBJECTIVE: To investigate the feasibility and therapeutic effect of acellular cadaveric dermis (ACD)-assisted immediate breast reconstruction. METHODS: From Sep. 2009 to May 2010, 10 cases received ACD-assisted immediate breast reconstruction. During the operation, the ACD was used to cover inferior and lateral portion of the implants in 2 cases and expanders in 8 cases. RESULTS: The patients were followed up for an average period of 4 months with satisfactory breast appearance. The complications included infection in 2 cases and dehiscence in 2 cases. But no implant or expander was taken out. CONCLUSIONS: The ACD assisted immediate breast reconstruction is a technically simple procedure with minimal morbidity. Satisfactory clinical outcome can be achieved with appropriate candidates. PMID- 22097308 TI - [Check ligament suspension for correction of congenital severe blepharoptosis]. AB - OBJECTIVE: To evaluate the clinical result of check ligament suspension for correction of congenital severe blepharoptosis. METHODS: Since Jan. 2010 to Nov. 2010, 15 eyes in 15 cases with congenital severe blepharoptosis were treated with the check ligament suspension. Palpebral aponeurosis was exposure by opening fascia palpebral during blepharoplasty. Palpebral aponeurosis was cut off about 5 mm above the tarsus. The check ligament was seen in the intermuscular space between the segment of levator and the anterior one third of superior rectus attached to the conjunctival fornix. Congenital blepharoptosis could be corrected by suturing the check ligament and levator palpebrae superior to the upper margin of tarsal plate with 3-0 silk thread. Double eyelid plasty was carried out in the end. RESULTS: The follow-up period was 3-11 months with good cosmetic result. All the cases could close their eyes in 15 to 30 days with no complication. CONCLUSIONS: In conclusion, this technique is quite successful in raising the level of the upper eyelid in severe congenital blepharoptosis. The check ligament moves in a similar direction as the natural movement of levator muscle, so both the postoperative static and dynamic appearance of the upper lid is more natural. PMID- 22097309 TI - [Auricular reconstruction for concha-type microtia]. AB - OBJECTIVE: To investigate the method of auricular reconstruction for concha-type microtia. METHODS: Two-staged auricular reconstruction was applied in 13 cases (14 ears) with concha-type microtia. The cartilage auricular framework was fabricated and implanted in the first stage, followed by ear elevation and cranio auricle angle formation at the second stage. RESULTS: The patients were followed up for 2 months to 2 years with satisfactory aesthetic result. The reconstructed ears had a good appearance and position, and were symmetric to the healthy ears. CONCLUSIONS: The two-staged auricular reconstruction with autologous cartilage framework is ideal for concha-type microtia. PMID- 22097310 TI - ["W-shape" flap at nasal tip for the correction of the nasal deformity secondary to unilateral cleft lip]. AB - OBJECTIVE: To investigate an effective method for the correction of the narrow nostril secondary to cleft lip. METHODS: A "bird wing shape" incision was made on the nasal tip to form a "W-shape" flap for repairing the nasal deformities secondary to cleft lip, especially for the cases with narrow nostril. RESULTS: Twenty-eight patients were treated with this method. All the cases achieved a symmetry shape of nasal ala, nostril, nasal columella and a normal height of nasal tip except for 2 cases with malformation at nasal tip who achieved improvement after reoperation. 21 cases were followed up for 6-12 months with good cosmetic result and no recurrence. CONCLUSIONS: "W-shape" flap at the nasal tip is an ideal way for the correction of mild to moderate narrow nostril deformity secondary to cleft lip. PMID- 22097311 TI - [Application of free anterior serratus musculo-fascial flap in bridge style for the soft tissue defect at leg]. AB - OBJECTIVE: To investigate the application of free anterior serratus musculo fascial flap in bridge style for the soft tissue defect at leg. METHODS: From Sept. 2006 to Jan. 2009, the free anterior serratus musculo-fascial flaps were used in bridge style in 7 cases with soft tissue defects at legs. The anterior serratus musculo-fascial flaps were elevated with subscapular and circumflex scapular vessels forming a T-shaped vascular pedicles. The T-shaped pedicle was end-to-end anastomosed with the two ends of the posterior tibial artery at the healthy leg. The musculo-fascial flap and its pedicle were covered with skin graft. RESULTS: All the 7 flaps survived completely with satisfactory result. The patients were followed up for 9-42 months with good functional and esthetic result both in donor site and recipient site. The patency of posterior tibial artery was demonstrated by clinical and Doppler examination. CONCLUSIONS: This technique is particularly useful in leg reconstructive surgery when only one vessel remains. The patency of the posterior tibial artery at the healthy leg is preserved and the morbidity in donor site is minimal. PMID- 22097312 TI - [Application of V-Y flap pedicled with superior malleolus cutaneous branch for small skin defect at the dorsal side of foot]. AB - OBJECTIVE: To investigate the therapeutic effect of V-Y flap pedicled with superior malleolus cutaneous branch for small skin defect at the dorsal side of foot. METHODS: From Aug. 2008 to Aug. 2010, 9 cases with skin defects at the dorsal side of feet were treated by V-Y flaps pedicled with superior malleolus cutaneous branch. The flap size ranged from 6.0 cm x 5.5 cm to 12.0 cm x 6.5 cm. The defects at the donor sites were closed directly. RESULTS: All flaps survived completely. 9 cases were followed up for 6-12 months after operation. The flaps had good texture and color match. The 2-point discrimination distance at the flap was 10-14 mm. The function of ankle was normal. CONCLUSIONS: The V-Y flap pedicled with superior malleolus cutaneous branch is ideal for the treatment of small skin defect at the dorsal side of foot. PMID- 22097313 TI - [Koyanagi technique for repairing proximal hypospadias with penoscrotal transposition]. AB - OBJECTIVE: To investigate the application of Koyanagi technique for repairing proximal hypospadias with penoscrotal transposition. METHODS: Koyanagi procedure was used for repairing proximal hypospadias with penoscrotal transposition in 26 boys (mean age 4.2 years) between July 2005 and June 2010. RESULTS: Primary healing was achieved in 22 cases. Three patients suffered from urinary fistula and the external urethral orifice in one patient was retracted to penis coronary sulcus, who were re-operated successfully. Two cases showed slight penile ventral curvature. Slight stricture of the urethral external orifice was noted in one case, which relieved after one to two times of urethral sounding every week for eight months. 20 patients were followed up for 6-36 months (mean 10.5 months) with good cosmetic result and normal urethra function. The penoscrotal transposition was also corrected. CONCLUSIONS: The original Koyanagi procedure might be one of the simple and effective method for repairing proximal hypospadias with penoscrotal transposition. PMID- 22097314 TI - [Different expression of TGF-beta1 and collagen during the healing process of wound infected by Pseudomonas aeruginosa]. AB - OBJECTIVE: To explore the different expression of TGF-beta1 and collagen during the healing process of wound infected by Pseudomonas aeruginosa (PAO1). METHODS: 24 female Wistar rats were randomly divided into pure wound group (group A) and wound + PAO1 group (group B). The re-epithelial rate, shrinkage rate and neutrophils number on the wounds were observed on the 1st, 3rd, 7th and 10th day after operation. The expression of TGF-beta1 and collage I, Ill was also detected. RESULTS: On the 7th day, the re-epithelial rate in group A was higher than that in group B, while the shrinkage rate in group A was lower than that in group B. The neutrophils number increased to peak on the 1st day in group B, but on the 3rd day in group A. The TGF-beta1 expression increased after operation in both groups, but it decreased in group B on the 3rd day and re-increased after that. The TGF-beta1 expression was significantly different between the two groups on the 7th day (P < 0.05). The expression of collagen I and III decreased during healing. The expression of collagen III in group A was higher on the 3rd day and was lower on the 7th and 10th day than that in group B, showing a significant difference (P < 0.05). CONCLUSIONS: PAO1 infection could delay the expression of TGF-beta1 and collagen I, III on wound, which may interfere the healing process of wound. PMID- 22097315 TI - [Construction of recombinant lentiviral vector of Tie2-RNAi and its influence on malignant melanoma cells in vitro]. AB - OBJECTIVE: To construct lentivector carrying Tie2-Small interfering RNA (SiRNA), so as to study its influence on malignant melanoma cells. METHODS: Recombinant plasmid pSilencer 1.0-U6-Tie2-siRNA and plasmid pNL-EGFP were digested with XbaI, ligated a target lentiviral transfer plasmid of pNL-EGFP-U6-Tie2-I or pNL-EGFP-U6 Tie2-II, and then the electrophoresis clones was sequenced. Plasmids of pNL-EGFP U6-Tie2-I and pNL-EGFP-U6-Tie2-II were constructed and combined with pVSVG and pHelper, respectively, to constitute lentiviral vector system of three plasmids. The Lentiviral vector system was transfected into 293T cell to produce pNL-EGFP U6-Tie2- I and pNL-EGFP-U6-Tie2-II lentivirus. Then the supernatant was collected to determine the titer. Malignant melanoma cells were infected by both lentiviruses and identified by Realtime RT-PCR to assess inhibitory efficiency. RESULTS: The recombinant lentiviral vectors of Tie2-RNAi were constructed successfully which were analyzed with restriction enzyme digestion and identified by sequencing. And the titer of lentiviral vector was 8.8 x 10(3)/ml, which was determined by 293T cell. The results of Realtime RT-PCR demonstrated that the lentiviral vectors of Tie2-RNAi could infect malignant melanoma cells and inhibit the expression of Tie2 genes in malignant melanoma cells (P<0.01). There was no significant difference in the expression level (P>0.05) between the two lentiviral vectors of Tie2-RNAi. CONCLUSIONS: Lentivector carrying Tie2-SiRNA can be constructed successfully and inhibit the expression of Tie2 gene in vitro significantly. The study will supply the theory basis for the further research on the inhibition of tumor growth in vivo. PMID- 22097316 TI - [Construction and transplantation of tissue-engineered skin with mouse embryonic fibroblasts in SD mice]. AB - OBJECTIVE: To investigate the application and mechanism of tissue-engineered skin with mouse embryonic fibroblasts (MEFs) for the full-thickness skin defects on mice. METHODS: The MEFs and fibroblasts were cultured and seeded in scaffold made of rat tail collage. ELISA method was used for detection of secretory function. The full-thickness skin defects were created on mice and covered by MEFs-scaffold complex (experimental group), or FBs-scaffold complex (control group 1), or scaffold only (control group 2). The process of wound healing was evaluated by observation of the re-epithelization rate. Microvessel density (MVD) and vimentin within the wound sites were also detected with immunohistochemistry staining technique to describe the characteristics of wound healing. Hoechst 33342 staining was performed to trace MEFs'fate. RESULTS: MEFs scaffold group had higher level secretion of IL-6 and lower of TGF-beta1 than FBs scaffold group (P<0.05). Compared with wounds in control groups, the wounds in MEFs group healed markedly fast (P<0.05) and the MVD was significantly higher (P <0.05). The fibroblasts in the wounds of MEFs group were arranged regularly and the MEFs decreased during the healing process. CONCLUSIONS: The MEFs-scaffold complex can promote wound healing with less scar formation. MEFs may have an inducing effect on the wound healing. PMID- 22097317 TI - [The effect of integrin-linked kinase on VEGF expression in fibroblasts from human hypertrophic scar]. AB - OBJECTIVE: To explore the expression of integrin-linked kinase (ILK) and its effect on VEGF expression in fibroblasts from human hypertrophic scar. METHODS: Fibroblasts were isolated from hypertrophic scar of 8 patients and cultured in vitro. Then the cells were divided into three groups: (1) Cells were cultured only in DMEM containing 10% FCS in the control group; (2) Cells were transfected with empty plasmid in the empty plasmid group; (3) Cells were transfected with plasmid expressing ILKcDNA in the ILK cDNA plasmid transfection group. First, the expression of ILK and VEGF was observed by immunocytochemistry before and after ILK cDNA transfection. Second, ILK and VEGF mRNA expression was investigated by real-time PCR (RT-PCR). Third, the protein expression of ILK and VEGF was detected by Western blot. Finally, the protein level of VEGF in supernatant of fibroblasts was measured by ELISA. RESULTS: Before ILK cDNA transfection, the expression of ILK was positive and the VEGF expression was weak in cytoplasm of fibroblasts . After ILK cDNA transfection, both the expression of ILK and VEGF was enhanced. The level of VEGF mRNA was significantly higher in ILK cDNA transfection group (0.338 +/- 0.060) than that in control group (0.022 +/- 0.001) and empty plasmid group (0.028 +/- 0.005, P < 0.05). The level of VEGF protein was significantly higher in ILK cDNA transfection group (0.819 +/- 0.019) than that in control group (0.607 +/- 0.033) and empty plasmid group (0. 591 +/- 0.024, P<0. 05). Secretion of VEGF increased remarkably in ILK cDNA transfection group comparing with the other two groups (P < 0.05). CONCLUSIONS: ILK could up regulate the VEGF mRNA and protein level in human scar fibroblasts. It may play an important role in the angiogenesis in hypertrophic scar. PMID- 22097318 TI - [Different expression of protein in the supernatant of heat injured keratinocytes]. AB - OBJECTIVE: To compare the difference of protein expression in the supernatant of heat injured keratinocytes (KC) and normal KC. METHODS: A model of heat injured KC was produced in vitro. The supernatant of normal KC and heat injured KC was collected after culture for 12 hours, and was ultrafiltered and lyophilized to get the protein. The protein sample was separated by immobilized pH gradient based two dimensional gel electrophoresis (2-DE). The gel was stained and the different expression of protein was analyzed using ImageMaster 2D analysis software. RESULTS: (1) Average protein spots were 1,898 +/- 113, 1,877 +/- 97 in the supernatant of normal and heat injured KC and 1,118 protein spots could be used for statistical analysis. (2) Statistical result showed that 26 protein spots were significantly different between the two groups. 16 protein spots were higher in the supernatant of normal KC and then 10 protein spots were lower in the normal group. (3) 16 protein spots, which included 10 kinds of proteins, were identified successfully as different spots. Lower expression proteins were alpha enolase, actin cytoplasmic 2, peroxiredoxin-4, phosphoglycerate mutase 1, G protein-regulated inducer of neurite outgrowth l in the supernatant of heat injured KC. Higher expression proteins in heat KC were purine nucleoside phosphorylase, tumor necrosis factor ligand superfamily member 10, proteasome subunit alpha type-7, UDP-glucose 6-dehydrogenase in the supernatant of heat injured KC. CONCLUSIONS: The result indicated that there are some significant different expression proteins in the supernatant of normal KC and heat injured KC. These findings provide new data for screening major molecules of tissue repair and finding the mechanism of wound repair. PMID- 22097319 TI - [Effects of pyrroloquinoline quinone on proliferation and expression of c-fos, c jun, CREB and PCNA in cultured Schwann cells]. AB - OBJECTIVE: To investigate the effects of pyrroloquinoline quinine (PQQ) on proliferation and expression of c-fos, c-jun, CREB and PCNA in cultured Schwann cells. METHODS: Schwann cells were cultured and purified in vitro. The purity of Schwann cells was identified by immunofluorescence of S-100. After synchronization of cell cycle by serum-free medium, different concentration of PQQ (0,1, 10, 100, 1,000, 10,000 nmol/L) were added into culture medium for 72 h. Flow cytometry was used to determine cell cycle. The content of c-fos, c-jun, and CREB mRNA were detected by RT-PCR, and the expression of PCNA protein was detected by Western blot. RESULTS: After PQQ treatment, the percentage of cells in G0/G1 phase decreased and the percentage of cells in S and G2/M phase increased. After treated by PQQ at concentration of 1-10,000nmol/L, content of c fos,c-jun,CREB mRNA was increased by 0.33,0.42 and 0. 52 fold (P < 0. 05). However, at concentration of 1 000 nmol/L, there was no difference in mRNAs content when compare to control (P >0.05). And it showed a decline at concentration of 10,000 nmol/L (P < 0.05). PCNA protein expression was up regulated at PQQ concentration of 1-100 nmol/L. At 100 nmol/L, the expression increased by 1.17 fold (P < 0.05); However, at 1,000 nmol/L, there was no difference in PCNA expression when compared to control. And 10,000 nmol/L of PQQ inhibited the expression of PCNA (P < 0.05). CONCLUSIONS: When treated with PQQ at concentration of 10-100 nmol/L, the proliferation of Schwann cells increased and the expression of c-fos,c-jun, CREB and PCNA was up-regulated. PMID- 22097320 TI - [Effects of PEG stress on flavonoids accumulation and related gene expression in suspension of Scutellaria baicalensis]. AB - OBJECTIVE: To study the effects of PEG stress on baicalin, baicalein accumulation induced by an increased concentration of PEG solution and the related genes' expression in suspension of Scutellaria baicalensis. METHOD: The content of baicalin, baicalein in suspension of S. baicalensis was determined by HPLC. The related genes' expression was analyzed by semi-quantitative PCR. RESULT: The content of proline in suspension of S. baicalensis was promoted by PEG treatment. Ten percent PEG treatment promoted the expression of PAL and the content of baicalein in experimental material via a drought stress. 20% PEG solution treatment promoted the expression of UBGAT. At the same time, the increased activity of APX inhibited the progress of eliminating reactive oxygen by baicalein, which induced the transformation from baicalein to baicalin. CONCLUSION: Active ingredient in suspension of S. baicalensis was promoted significantly via a stress of light concentration of PEG solution. PMID- 22097321 TI - [Dynamic accumulation of effective components and biomass of Coptis chinensis in Hongya county]. AB - OBJECTIVE: To study the dynamic accumulation of the effective components and biomass of Coptis chinensis, so to provide the experimental date of optimal harvest time for C. chinensis in Hongya county. METHOD: The samples of three to five years were gathered from the same field and time. The biomass was analyzed by weighed. The jatrorrhizine, columbamine, epiberberine, coptisine, palmatine and berberine in C. chinensis were analyzed by HPLC. RESULT: With the increasing of years of growth, the rootstalk biomass of C. chinensis was increasing continuously. The biomass growth of four-year-old C. chinensis was the fastest in the year. From September to October was the fastest season of the growth of rootstalk. The dynamic accumulation in rootstalk C. chinensis had regularity in the certain extend. The contents of six alkaloids and all alkaloids in 4-year-old C. chinensis were more than that in 3-years-old and 5-year-old. The contents of six alkaloids were mostly highest in August. From July to December, there is no significant difference in the contents of columbamine, epiberberine, coptisine, palmatine, berberine and all alkaloids in 4-years-old C. chinensis. CONCLUSION: According to the biomass and the accumulation pattern of the effective components in the C. chinensis, the optimal harvest time is from September to October of 4 year-old C. chinensis. PMID- 22097322 TI - [Studies of floral biology, breeding characters of Lamium barbatum]. AB - OBJECTIVE: To reveal the flowering characteristics and provide theoretical basis for the breeding and cultivation of Lamium barbatum. METHOD: The field observation and investigation of blooming phenophase were applied in the study growth dynamics of inflorescence and the period of the floret were measured. Then the statistic analyses of them were carried out. The pollen viability was evaluated by TTC test and the stigma receptivity was evaluated by benzidine-H2O2 method. RESULT AND CONCLUSION: The flowers of L. barbatum were bisexual, with 4 to 14 flowers in an inflorescence. The population came into bloom from April to June and the blossom of a single flower could last about 3 days. Pollination peak lasted 8 hours from the very beginning of blooming, and the high stigma receptive stage remained during the same period of time. The results indicated that the breeding system of L. barbatum was outcrossing with self-compatibility and pollinators were needed based on the outcrossing index. The most frequent floral visitors were bees. The suitable breeding strategy was also discussed. PMID- 22097323 TI - [Effects of AM fungi on growth and microelement of Scuteliaria baiealensis under different applied phosphorous levels]. AB - The effects of AM fungi on the growth, nutrient uptake and microelement of Scutellaria baicalensis under different applied phosphorous levels in the pot culture were studied. The results showed that applied phosphorous levels had remarkable effect on AM fungal inoculation. Inoculation effect of AM fungi was the best under 0.12-0.18 g x kg(-1) soil. At those levels, the effect of AM fungi on the growth of S. baicalensis was the best, but either lower or higher phosphorous level showed suppressed infecting of AM fungi to S. baicalensis. After inoculation, the contents of biomass, total P, baicalin, total N of root were increased as well as the microelements of K, Ca, Mg, Fe, Zn, but the contents of total N of shoot, N/P were decreased as well as the microelements of Mn, Cu. In conclusion, the growth of host plant and using rate of phosphorus fertilizer can be promoted by inoculation of AM fungi. PMID- 22097324 TI - [Structures and bioactivity of polysaccharides from isatidis radix]. AB - OBJECTIVE: To investigated the chemical structures and bioactivity of polysaccharides from Isatidis Radix. METHOD: Polysaccharides were extracted and purified by column chromatograph and their chemical structures were identified by UV, IR, NMR, periodic acid oxadation and Smith degradation method and their stimulation effects to macrophage were evaluated by using MTT method. RESULT: Five polysaccharides, polysaccharide A , B, C, D and E were gotten and their molecular weights were 2 000, 1 757.1, 1 34 2.7, 955.6, 11.7 kDa, respectively. Polysaccharide A was composed of arabinose, polysaccharide E was composed of arabinose and galactose, polysaccharides B, C, D were composed of glucose and 1 - > 2, 1 --> 3, 1 --> 4, 1 --> 6 linkages existed in polysaccharides A-E, of A, B, C, D, E were alpha-configurations. Polysaccharides B, C and D showed better bioactivity than polysaccharides A and E with stimulation index (SI) of 5.31, 4.76, 5.17. CONCLUSION: Five polysaccharides are seperated firstly from Isatidis Radix. PMID- 22097325 TI - [Extraction and antioxidant activity of collagen from elephant skin, pig skin and fish scales]. AB - OBJECTIVE: To study collagen structure of the traditional Chinese medicine elephant skin and the proposed alternatives such as pig skin, fish scale, and antioxidant activity. METHOD: Orthogonal experimental design method was employed to determine the optimal extraction condition of collagen from the elephant skin, and the structure and content of collagen of proposed alternatives were compared, their scavenging ability were determined by salicylic acid. RESULT: Collagen extracted from elephant skin with the optimal conditions was the structural integrity and good quality first time, and collagen structure of the elephant skin was similar to the proposed alternatives. Free radical scavenging capacity of collagen, values of IC50, were 0.51 g x L(-1) of elephant skin, 0.60 g x L(-1) of pig skin and 0.42 g x L(-1) of fish scale. CONCLUSION: By comparing and identification of proteins that the collagen of elephant skin is type I collagen, with a strong antioxidant capacity, is the active ingredients of elephant skin. It provides a further study of alternatives as an important reference. PMID- 22097326 TI - [Comparative analysis of volatile fractions in Polygonati rhizoma and its processed products by GC-MS]. AB - OBJECTIVE: To conduct comparative study on the volatile components from Polygonati Rhizoma during processing. METHOD: Volatile oil was obtained from Polygonati Rhizoma by steam distillation (SD). Volatile components were concentrated by a purge and trap-thermal desorption (P&T-TD) method, and analyzed with gas chromatography-mass spectrometry (GC-MS), which were comparative by analyzed with the method of SD-GC-MS simultaneously. RESULT: The change in quantity and quality of volatile components in pre and post processed Polygonati Rhizoma were observed. Fifty-one compounds were checked out with SD-GC-MS, while 11 compounds with P&T-TD-GC-MS. CONCLUSION: This study is useful to illustrate the mechanism of decreasing toxicity and stimulating components after being processed. PMID- 22097327 TI - [Extraction, purification technology and antineoplastic effects of solamargine]. AB - OBJECTIVE: To extract and purify of solamargine from Solanum nigrum, and to research its antineoplastic effects. METHOD: S. nigrum was extracted refluently with 80% alcohol, solamargine was purified with silica gel column chromatography and recrystallization, and then conducted its structure identification and purity checks. Screened the effect on human tumor cell groth inhibition in vitro by MTT assay, and researched on the features in mice with H22 liver cancer or Ehrlich ascites tumor of solamargine. RESULT: The concent of solamargine reached 97.9%. Solamargine had significantly inhibition on 6 tumor cells in vitro, and it had significantly inhibition on mice with H22 liver cancer or ehrlich ascites tumor in the 2.4 mg x kg(-1) dose of i.v. CONCLUSION: Solamargine have the antineoplastic effect. PMID- 22097328 TI - [Study on in vitro release of xingnaojing microemulsion]. AB - OBJECTIVE: To study in vitro release of Xingnaojing microemulsion and to investigate the release mechanism. METHOD: The concentration of jasminoidin was determined by HPLC and the concentration of Aipian was determined by GC. In vitro release characteristics were conducted by dialysis technique. Model fitting was used to determine the kinetics and mechanism. RESULT: Jasminoidin released completely within 2 h, fitting the Weibell model best. The release of borneol fitted first order model. CONCLUSION: The release mechanisms of different types of medicines are quite different. The different types of medicines dissolve in the different phases in the microemulsion. PMID- 22097329 TI - [Study on pharmacokinetics of borneol in rats injected with novel-xingnaojing by GC-FID]. AB - OBJECTIVE: To develop a GC-FID method for the determination of borneol concentration in rat plasma and to investigate the pharmacokinetics after injection of novel-Xingnaojing. METHOD: Novel-Xingnaojing was injected via by caudal vein injection. The blood samples were collected by posterior orbital venous plexus approach at 0.5, 1, 3, 5, 8, 12, 20, 30, 45 min. The drug in plasma was extracted with ethyl acetate and then detected by GC-FID, octadecane was used as the internal standard. The pharmacokinetic parameters were calculated by the software of Kinetica. RESULT: The calibration curve was good linear in the range of 1.67-16.67 mg x L(-1). The extraction recoveries of low, medium and high concentration were (92.81 +/- 1.11)%, (85.38 +/- 0.86)% and (84.58 +/- 0.58)%, respectivley. And the RSDs of within-day and between-day were below 3.00%. Plasma concentration of borneol was consistent with the two-compartment open model. The pharmacokinetic parameters were that the t1/2alpha was (1.18 +/- 0.20) min, the t1/2beta was (22.27 +/- 6.85) min, the C(max)(Calc) was (18.76 +/- 2.10) mg x L( 1), the MRT was (23.84 +/- 7.67) min(-1), and the AUC was (100.00 +/- 15.85) mg x min x L(-1). CONCLUSION: The GC-FID method developed can be applied to determination and pharmacokinetics. The borneol in novel-Xingnaojing is distributed and metabolized fast after being administrated. PMID- 22097330 TI - [Studies on chemical constituents of Rabdosia serra]. AB - OBJECTIVE: To study the chemical constituents of aerial part of Rabdosia serra. METHOD: The compounds were isolated by extraction, coloum chromatography over silica gel and ODS, and preparative HPLC. Their structures were identified by various spectroscopic methods including MS, IR, 1D and 2D NMR data. RESULT: Six compounds were isolated from R. serra and were characterized as ent-1alpha, 7alpha, 14beta, 20-tetrahydroxy-11, 16-kauradien-15-one (1), kamebakaurin (2), dihydrokamebakaurin (3), rabdoinflexin A (4), daucosterol( 5), and beta sitosterol (6). CONCLUSION: Compound 1 is a new compound, and coumpound 3 was obtained from this plant for the first time. PMID- 22097331 TI - [Chemical constituents from Bufonis periostracum and their antitumor activity in vitro]. AB - Eight compounds were isolated from Bufonis periostracum by repeated column chromatography on silica gel, ODS and Sephadex LH-20 and their structures were characterized as palmitatic acid cholesteryl ester (1), cholesterol (2), 5alpha, 8alpha-epidioxycholesta-6-en-3beta-ol (3), cholest-5-en-3beta, 7beta-diol (4), cholest-7-en-3beta, 5alpha, 6beta-triol (5), 3-octaddecyloxy-1, 2-propanediol (6), isisamide (7) and bufothionine (8) on the base of spectral analysis. Compounds 1-8 were isolated from Bufonis periostracum for the first time and compounds 3, 5, 6, 7 were obtained from Bufo bufo gargarizans and Bufo genus for the first time. The bioassays showed all tested samples displayed no antitumor activity against the cell lines such as A549, BeL 7402, HGC-27 and HL-60, except the control compound bufalin. PMID- 22097332 TI - [Isoprenoids and phenylpropanoids from Saussurea deltoidea]. AB - To investigate the chemical constituents of Saussurea deltoidea, 10 compounds were isolated from the title plant by various chromatography methods such as silica gel, RP-18 silica gel, Sephadex LH-20 column chromatography, HPLC, et al. Their structures were elucidated by spectral analysis. Five isoprenoids and Five phenylpropanoids were isolated and elucidated as (3R, 6R, 7E) -3-hydroxy-4, 7 megastigmadien-9-one (1), (3S, 5R, 6S, 7E) -5, 6-epoxy-3-hydroxy-7-megastigmen-9 one (2), 3-hydroxy-beta-damascone (3), S-(+) -dehydrovomifoliol (4), megastigman 5-ene-3beta, 9R-diol (5), coniferaldehyde (6), beta-hydroxypropiovanillone (7), 3 hydroxy-1-(4-hydroxy-3, 5-dimethoxyphenyl) -1-propanone (8), dihydrosyringenin (9), 4-[(1S) -3-hydroxy-1-methoxypropyl]-2, 6-dimenthoxyphenol (10). All the compounds were isolated from S. deltoidea for the first time. PMID- 22097333 TI - [Chemical constituents of Swertia hispidicalyx]. AB - OBJECTIVE: To study the chemical constituents of Swertia hispidicalyx. METHOD: The EtOAc part of S. hispidicalyx was chromatographied by various column chromatography methods, and the isolates were identified based on spectroscopic analyses (MS, 1H-and 13C-NMR). RESULT: Eleven compounds were isolated from S. hispidicalyx and characterized as 1,3,5,8-tetrahydroxyxanthone (1), 1,5,8 trihydroxy-3-methoxyxanthone (2), gentiolactone (3), swertiamarin (4), 3,4 dihydro-1H,6H,8H-naphtho [1, 2-c:4, 5-c', d'] dipyrano-1,8-dione (5), (+) syringaresinol (6), trans-coniferyl aldehyde (7), maslinic acid (8), oleanolic acid (9), daucosterol (10), and -sitosterol (11). CONCLUSION: Compounds 1-11 were obtained from S. hispidicalyx for the first time. PMID- 22097334 TI - [Simultaneous determination of six flavonoids in Hyperici Japonici Herba by HPCE DAD]. AB - OBJECTIVE: To establish a high performance capillary electrophoresis method with diode array detection (HPCE-DAD) for simultaneous determination of rutin, isoquercitrin, hyperoside, quercitrin, kaempferol and quercetin in Hyperici Japonici Herba. METHOD: Based on the mode of capillary zone electrophoresis, 40 mmol x L(-1) borax was used as buffer solution (pH 8.62), uncoated fused silica capillary (56 cm x 64.5 cm x 75 microm) was used, separation voltage was 25 kV, detection wavelength was at 206 nm, column temperature was maintained at 25 degrees C, and sample was injected at 50 mbar, 8 s. RESULT: Six flavonoids showed good linearity (r > 0.9953) in the range of the tested concentration, the average recoveries of the method were between 98.8%-102.9%. CONCLUSION: The method is simple, accurate and reproducible, and can be used for quality control of Hyperici Japonici Herba. PMID- 22097335 TI - [Simultaneous determination of 4 nortriterpenoids in Schisandra chinensis extract by HPLC]. AB - OBJECTIVE: To determine 4 nortriterpenoids (de-hydroxy arisanlactone D, 25 hydroxy schindilactone, schindilachone A, lancifodilactone D) in Schisandra chinensis extract by HPLC. METHOD: The analysis was performed on a waters symmetry column (4.6 mm x 250 mm, 5 microm) with the mobile phase of acetonitrile water (33:67) at a flow rate of 1 ml x min(-1). The column temperature was set at 37 degrees C, and the detector wavelength was 264 nm. RESULT: The linear ranges of de-hydroxy arisanlactone D, 25-hydroxy schindilactone, schindilachone A, and lancifodilactone D are 0.075-1.800, 0.098-0.980; 0.095-0.950, and 0.053-0.530 microg, respectively, and the average recoveries were 98.57%, 96.44%, 97.96%, and 97.27%, respectively. CONCLUSION: The four nortriterpenoids were well separated by this method, and it could be used to determine the four nortriterpenoids in Schisandra chinensis extract. PMID- 22097336 TI - [Study on constituents of essential oil from Lonicera fulvotomentosa in different collected periods]. AB - OBJECTIVE: To extract and identify the chemical constituents of essential oil from Lonicera fulvotomentosa in different collected periods (bud, Silver-flower and Golden-flower periods). METHOD: Extracts in three different collected periods were subjected to GC-MS analysis for determination of their chemical constituents. RESULT: The 29, 34 and 28 kinds of chemical constituents corresponding to the above three periods were found, and 44 kinds of compounds were identified. The relative content of every chemical constituents in each essential oil was obtained by area normalization method. CONCLUSION: The O-tolyl isocyanide was detected from essential oil of Lonicera for the first time. The result indicated that the highest relative content in essential oil in the three periods is alcohol substance and the second is ester and aldehyde. Many common constituents in the essential oil from L. fulvotomentosa, including linalool, hyacinthin, O-tolyl isocyanide, geraniol, methyl anthranilate, and so on, all could be detected in the three periods. However, the differences of their relative content are obvious. PMID- 22097337 TI - [Determination of atranol, lecanorin, ethyl orsellinate and methyl orsellinate in Usnea diffracta by RP-HPLC]. AB - OBJECTIVE: To develop a RP-HPLC method for determining the contents of atranol, lecanorin, ethyl orsellinate and methyl orsellinate in Usnea diffracta. METHOD: A Kromasil-C18 column (4.6 mm x 250 mm, 5 microm) was used at 25 degrees C with the mobile phases of acetonitrile -1% acetic acid in a gradient manner. The flow rate was set at 1.0 mL x min(-1). The detection wavelength was 280 nm. RESULT: The correlation coefficients of atranol, lecanorin, ethyl orsellinate, and methyl orsellinate were higher than 0.999. Recoveries were from 102.9% to 95.30%; with RSD from 2.3% to 1.9%. CONCLUSION: The method is quick, simple and repeatable for simultaneous determination of atranol, lecanorin, ethyl orsellinate and methyl orsellinate in U. diffracta. PMID- 22097338 TI - [Ocular pharmacokinetics of puerarin in anesthetic rabbits by microdialysis]. AB - OBJECTIVE: To establish the model of microdialysis, and study the ocular pharmacokinetics of puerarin in anesthetic rabbits. METHOD: Implanted the probe into anterior chamber of anesthetic rabbit by surgery. After balanced for 2 h, 1% puerarin eye drop (100 microL) was applied into the cul-de-sac with micropipette. Immediately the dialysate was collected at different time and detected by HPLC with the detection wavelength of 249 nm. The mobile phase was methanol and 0.1% citric acid solution (30:70); the flow rate was 1.0 mL x min(-1). RESULT: After the administration, puerarin can be absorbed into aqueous humor quickly. The peak concentration of puerarin appeared at about 1 h and then reduced gradually. The peak concentration(C(max)) is (2.52 +/- 0.31) mg x L(-1). The other lower peak was shown at 3.5 h during the eliminate phase. This might be attributed to the inhibition of aqueous humor production by the puerarin and resulted in a high drug concentration. The area under concentration-time curve (AUC(0-t)) is (5.04 +/- 0.21) mg x h x L(-1) and the eliminate half life (t1/2) is (0.38 +/- 0.13) h. CONCLUSION: The microdialysis technique can be used to detect the ocular pharmacokinetics of puerarin, and support the valuable pharmacokinetics parameter for the clinical applications of puerarin eye drop. PMID- 22097339 TI - [Comparative study on effect of icariin and genistein on proliferation and mineralization of osteoblasts in vitro]. AB - OBJECTIVE: To investigated the effect of icariin and genistein on proliferation and mineralization of cultured rat osteoblasts (rat calvarial osteoblasts, ROB). And to contrast the pharmacological activity of icariin and genistein. METHOD: Bone cells were obtained by enzyme digestion from the segregated neonatal SD rat skull, and were cultured in MEM containing 10% FBS which was changed after three days later. Serial subcultivation was proceeded when cells covered with 90% culture dish. The final action concentration of icariin and genistein were both 1 x 10(-5) mol x L(-1). Proliferation was analyzed by MTT on 96-well plates, while differentiation was analyzed on 24-well plates. Under the induced condition, the alkaline phosphatase activity, calcium salt sediment yield and osteocalcin were measured at the 3, 6, 9, 12 d. At 12th day, ALP staining, alizarin red staining and calcified nodule count were preceded. Total RNA was isolated at 0, 6, 12, 24, 48, 72 h. The gene expression of bFGF, IGF-1, Osterix and Runx-2 was analyzed by Real-time RT-PCR. RESULT: With the concentration of 1 x 10(-5) mol x L(-1), icariin and genistein have no significant effect on the ROB' s proliferation. The osteogenesis, ALP activity, calcium salt sediment yield and osteocalcin, calcified tubercle amount were significantly increased. And they enhanced the mRNA level of bFGF, IGF-1, Osterix and Runx-2. On the level of osteoblasts, the activity of icariin is stronger than that of genistein. CONCLUSION: When the final concentration of icariin and genistein is 1 x 10(-5) mol x L(-1), they can significantly promoted ROB maturation. And on the level of osteoblasts, the activity of icariin is stronger than that of genistein. PMID- 22097340 TI - [Studies on pharmacokinetics of hydroxysafflor yellow A in Carthamus tinctorius and its compound preparation in rat]. AB - OBJECTIVE: To develop a RP-HPLC method for the determination of the concentration of hydroxysafflor yellow A in rat plasma, to study the pharmacokinetics of Carthamus tinctorius extration and Naodesheng tablet, and to investigate the effect of other components on the pharmacokinetics of hydroxysafflor yellow A. METHOD: The rats were orally treated with Carthamus tinctorius extration and Naodesheng capsule respectively. Blood samples were collected in heparinized eppendorf tube via the oculi chorioideae vein. Plasma was separated by centrifugation at 10 000 r x min(-1) for 10 min, and two-times methanol in volume was added to deposit proteins. After centrifugation, the upper liquid was transferred to filter. The concentration of hydroxysafflor yellow A in serum was determined by RP-HPLC. The stationary phase was C18, and methanol-acetonitrile 0.7% orthophosphoric acid (26: 2:72) was taken as the mobile phase, A UV detector was used at 403 nm. The pharmacokinetic parameters were calculated with 3p97 program. RESULT: A good linear relationship of hydroxysafflor yellow A was obtained in the range of 0.03 and 2.56 mg x L(-1), the lowest limit of determination was 10 microg x L(-1), and the lowest limit of quantitation was 30 microg x L(-1). The mean recoveries were (99.3 +/- 1.4)%, (92.8 +/- 1.8)%, (98.4 +/- 2.0)% for high, middle, low concentrations of the samples respectively. The plasma concentration-time curves of hydroxysafflor yellow A were fitted with two compartments model. The AUC)0-t), AUC(0-infinity), C(max) and T(max) of hydroxysafflor yellow A were increased in the Naodesheng group, compared with 50 mg x kg(-1) C. tinctorius extract group. CONCLUSION: The HPLC method was selective, accurate and sensitive. The results indicated that the other herbs improved the absorption of hydroxysafflor yellow A and increased the bioavailability of hydroxysafflor yellow A significantly. PMID- 22097342 TI - [Puerarin induced apoptosis of pulmonary artery smooth muscle cell by mitochondrial pathway]. AB - OBJECTIVE: To investigate the contribution of mitochondrial pathway in the apoptosis induced by puerarin (PUE) in pulmonary artery smooth muscle cells. METHOD: Cultured rat pulmonary artery smooth muscle cells (PASMC) were intervened by high, middle and low dose of puerarin (1.5 x 10(-3), 1.5 x 10(-4), 1.5 x 10( 5) mol x L(-1)). The change of mitochondrial membrane potential was observed. Western blot detected the expression of apoptosis-related gene Caspase-9, Bax and Bcl-2 protein. RESULT: Compared with the control group, mitochondrial membrane potential significantly decreased in puerarin groups. Puerarin can enhance the expression of Caspase-9 and Bax protein, decrease the expression of Bcl-2 protein. Puerarin also has a concentration-dependent on the induction of PASMC. CONCLUSION: Puerarin can induce PASMC apoptosis through mitochondrial pathway. PMID- 22097341 TI - [Effect of epimedii folium processed with different refining temperatures and amounts of sheep's oil on kidney-yang deficiency rats]. AB - OBJECTIVE: To investigate the effects of refining temperatures and amounts of sheep's oil used in processing Epimedii Folium on Kedney-yang deficiency rats. METHOD: The corticosterone was subcutaneous injected to establish the kidney yang deficiency rat model. With the temperatures and amounts of sheep's oil were 250 degrees C/30%, 120 degrees C/30% and 120 degrees C/20% respectively, the crude drug and three kinds of pressed Epimedii Folium were extracted by water and used as examined samples while total flavonoid of Epimedii Folium was used as positive control. After examined samples and control samples were intragastirc administrated, the pharmacologic action was analyzed. RESULT: As compared to crude drug, all of the aqueous extracts of processed Epimedii Folium have stronger effect of warming kidney and enhancing yang, especially the Epimedii Folium processed by sheep's oil with refining temperatures 120 degrees C and amounts of sheep's oil 30%. Its mechanism might be related to improving the insufficiency of hypothalamic-pituitary-adrenal-thymus (HPAT) axis suppression. CONCLUSION: The refining temperature of sheep's oil can affect the quality of excipients and processed drugs. The results may be useful in explaining the mechanism of Epimedii Folium processing and establishment of pharmaceutical standard of sheep's oil used as processing excipients. PMID- 22097343 TI - [In vivo and in vitro effect of peptide HP-6 derived from donkey serum albumin on hematopoietic system]. AB - OBJECTIVE: By bioinformatics method, the effect in hematopoietic system of bioactive peptide HP-6, which was obtained from donkey serum albumin and is one of the major protein components from donkey-hide gelatin, was investigated. METHOD: Human bone marrow nucleated cells (hBMNCs) and murine bone marrow stromal cells (mBMSCs) were separated and cultured with different concentration of peptide HP-6 (0.000 15, 0.001 5, 0.015, 0.15, 1.5 micromol x L(-1)). The effect on promoting proliferation of cells related to hematopoiesis in bone morrow was detected and the ultrastructure of cells after treated by HP-6 was observed through transmission electron microscope. Hemorrhage anemia mouse model and anemia mouse model induced by cyclophosphamide were established, and randomly divided into peptide HP-6 groups which were administered respectively with different doses (1, 0.1, 0.01 mg x kg(-1)) by gavage, and control group which was administered with PBS by gavage. Peripheral blood components of all mice and bone morrow cells (BMC) number of mice induced by cyclophosphamide were evaluated. RESULT: Peptide HP-6 could concentration-related promote the proliferation of hBMNCs and mBMSCs, hBMNCs got the highest reproduction rate of 152.11% and mBMSCs also got 63.52% with the concentration of 0.15 micromol x L(-1), then the reproduction rate decreased while the concentration kept increasing. The transmission electron microscope showed that ultrastructure of cells was normal after treated by HP-6.1 mg x kg(-1) peptide HP-6 significantly increased peripheral platelet and protected mouse morrow injured by cyclophoshamide. 0.1 mg x kg(-1) peptide HP-6 significantly increased peripheral platelet with relative growth rate of 77.65%, increased peripheral white blood cells count and peripheral red blood cells count, also could protect mouse peripheral blood after treated by chemotherapeutics. CONCLUSION: Peptide HP-6 could promote the proliferation of cells related to hematopoietic system, enhance mouse hemopoiesis function and the resistance to chemotherapeutic injury. PMID- 22097344 TI - [Effectiveness of cultured Cordyceps sinensis combined with glucocorticosteroid on pulmonary fibrosis induced by bleomycin in rats]. AB - OBJECTIVE: To study the treatment effects of cultured Cordyceps sinensis combined with glucocorticosteroid on experimental pulmonary fibrosis in rats induced by bleomycin. METHOD: Fifty rats were randomly divided into five groups, including control group, model group, cultured C. sinensis groups, prednisone group, cultured C. sinensis combined with prednisone group. On experimental day 0, the rats were respectively intratracheally instilled with bleomycin, and rats in the control group and model group with the same volume of normal saline. One day after the injection, cultured C. sinensis and glucocorticosteroid was respectively given to rats daily by gastric gavage, while the same volume of normal saline was given to those in the control group and model group. On 28th d, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Histological changes of the lungs were evaluated by HE stain, Masson's trichrome stain. Collagen content of the lung tissue was assessed by hydroxyprolin concentration. Lung expression of CTGF protein was assessed by immunohistochemistry. The level of TGF-beta1 protein was measured by ELISA. RESULT: Compared to model group, pulmonary fibrosis were alleviated in cultured C. sinensis and prednisone group, and CTGF expression, Hydroxyproline concentrations and protein TGF-beta1 were decreased. The combination effect of C. sinensis and prednisone group is augmented compared with using C. sinensis or prednisone group alone. CONCLUSION: The cultured C. sinensis and prednisone alleviates pulmonary fibrosis, and the combination use of both drugs has synergia effects in anti-fibrous degeneration. PMID- 22097345 TI - [Effects of different compatibility proportion of jiaotai pills on treating type 2 diabetes mellitus in rats]. AB - OBJECTIVE: To study the effects of different compatibility proportion of Jiaotai pills on treating type 2 diabetes mellitus (T2DM) in rats. METHOD: The model of type 2 diabetes mellitus in rats was established by injecting streptozotocin from tail vein and feeding with high fat and high caloric diet. Diabetic rats were randomly divided into model group, Jiaotai pill 1 group (Coptidis Rhizoma cinnamon 2: 1), Jiaotai pill 2 group (Coptidis Rhizoma-cinnamon 4: 1), Jiaotai pill 3 group (Coptidis Rhizoma-cinnamon 10: 1) and metformin group. Rats in different treatment groups were given by corresponding therapy from gastric tube. Meanwhile normal control group was another set. Body weight, oral glucose tolerance test (OGTT), blood lipid level including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), plasma levels of free fatty acid (FFA) and adiponectin, plasma liver enzymes activity(ALT, AST, AKP, gamma-GT) and pathological results of liver tissue were determined after eight weeks. RESULT: Body weight, fasting plasma glucose (FPG), postpradial plasma glucose at one hour (PG-1 h), postpradial blood glucose at two hour (PG-2 h), plasma levels of TC, TG, LDL-C, FFA and liver enzymes activity were all increased in rats of model group compared with those in normal control group. Plasma levels of HDL-C and adiponectin were decreased in model group (P < 0.01). Fatty degeneration of hepatocytes was apparent in liver tissues in rats of model group. Compared with model group results of OGTT, blood lipid levels and liver enzymes activity were improved while levels of HDL-C and adiponectin were increased in rats of different treatment groups (P < 0.05 or P < 0.01). Meanwhile fatty degeneration of hepatocytes was improved in liver tissues in rats of different treatment groups. Compared with metformin group, plasma level of HDL-C was elevated while AKP and gamma-GT were decreased significantly in rats of Jiaotai pill 1 group (P < 0.05), gamma-GT level was decreased significantly in rats of Jiaotai pill 2 group (P < 0.05), AST, AKP and gamma-GT levels were decreased significantly in rats of Jiaotai pill 3 group (P < 0.05). Compared with Jiaotai Pill 1 group, plasma levels of HDL-C was decreased while AKP levels was elevated significantly in rats of Jiaotai pill 2 group, but HDL-C was decreased in rats of Jiaotai pill 3 group (P < 0.05). CONCLUSION: It is suggested that different compatibility proportion of Jiaotai pills are effective on treating type 2 diabetes mellitus in rats. The effect of Jiaotai pill 1 group is better than that of other therapy groups. PMID- 22097346 TI - [Clinical study on intervention of spleen-restoring decoction integrating with dormancy hygiene education on subhealthy insomnia of deficiency of both heart and spleen pattern]. AB - OBJECTIVE: To appraise the clinical efficacy, safety and compliance of the intervention of spleen-restoring decoction combined with dormancy hygiene education and the intervention of spleen-restoring decoction alone on sub-healthy insomnia of deficiency of both the heart and spleen pattern. METHOD: Study design took multi-centers, blind and randomized control trial, 107 participants with sub healthy insomnia of deficiency of both the heart and spleen pattern were assigned to A group (52 cases) which was treated with the intervention of spleen-restoring decoction combined with dormancy hygiene education and B group (55 cases) which was treated with the intervention of spleen-restoring decoction single, compared by efficacy, PSQI score, CGI score, WHOQOL-BREF score and security. RESULT: The efficacy of two group was 79.58%. There was no significant different between them. The PSQI scores before treatment was (11.80 +/- 2.08) and which afer treatment was (6.78 +/- 2.84) of A group. The PSQI scores before treatment was (11.61 +/- 2.00) and which afer treatment was (6.73 +/- 2.27) of B group. There was significant difference in PSQI scores both A group and B group after treatment (P < 0.01); the results of CGI score and WHOQOL-BREF score before and after measurement showed the same as PSQI. There were no significant difference between two groups in all scores after treatment and there was no interaction between time pots and treatment factors . Withdrawal reaction analysis: comparing CGI after withdraw 2 weeks and at the end of treatment course, there was no significant difference between two groups. The same result was in comparison among groups. CONCLUSION: Both the intervention of spleen-restoring decoction integrating with dormancy hygiene education and spleen-restoring decoction had obvious clinical efficacy on treating subhealthy insomnia of deficiency of both the heart and spleen pattern, and had high compliance and safety. The intervention of spleen-restoring decoction integrating with dormancy hygiene education showed no better clinical efficacy than spleen-restoring decoction did. PMID- 22097347 TI - [Effects of Ginkgo biloba extract on anticoagulation and blood drug level of warfarin in healthy wolunteers]. AB - OBJECTIVE: To study the effects of Ginkgo biloba extract (GBE) on the pharmacokinetics and pharmacodynamics of warfarin and observe the anticoagulant activity of GBE. METHOD: A randomized, double-blinded, placebo-controlled, two way cross-over trial was conducted. Twelve healthy volunteers (sex ratio was 1: 1) were randomized into two groups and received GBE (three pill, tid) or placebo (three pill, tid) for 5 weeks respectively. the subjects received a single dose of warfarin (5 mg) on the day 29. Blood samples for pharmacokinetics and pharmacodynamics assessment were collectd. RESULT: Compared with placebo, BE had no significant pharmacodynamics effects on warfarin and had no effects on prothrombin time (PT) and activated partial thromboplastin time (APTT). GBE extract increased C(max), AUC(0-144 min), AUC(0-infinity), t1/2, of warfarin significantly and decreased CL(F) of warfarin significantly (P < 0.05), and there were no singnificant difference of V(d) (F). CONCLUSION: GBE has limited effects on the pharmacokinetics but no effects on the pharmacodynamics of single dose warfain in health subjects. GBE has no effects on clotting process alone. PMID- 22097348 TI - [Effects of sanjin tablets on T lymphocyte subsets of peripheral blood of women with recurrent urinary tract infection]. AB - OBJECTIVE: To observe the impact of Sanjin tablet on the T lymphocyte subsets of the peripheral blood of female patients with recurrent urinary tract infection, to reveal the immune pharmacological mechanism of its prevention and treatment of the disease. METHOD: A randomized, controlled and open trial was adopted. The 68 patients were divided into treatment group (30 cases) and control group (28 cases). Two groups were both treated with conventional sensitive antibiotics, the treatment group took Sanjin tablet in addition. After bacteria in the urine were negative, the treatment group took maintenance therapy with Sanjin tablet for 3 months, the control group took appropriate low-dose antibiotics maintenance treatment for 3 months. The peripheral blood T lymphocyte levels before and after treatment, time from the initial treatment to the bacterial culture of urine was negative of the two groups, and the recurrence rate of urinary tract infection in 3 months after discontinuation of the two groups were observed. RESULT: After treatment, the CD3+, CD4+ T cells and CD4+/CD8+ in peripheral blood of the treatment group were enhanced compared with untreated and the control group (P < 0.05). Time from the initial treatment to the bacterial was negative and the recurrence rate of the treatment group were significantly better than the control group (P < 0.01). CONCLUSION: Effective treatment with Sanjin tablet to the recurrent urinary tract infection of female patients will probablely through the mechanism of improving the cell-mediated immunity levels to achieve the effect of shortening the course of treatment and to reducing the recurrence rate. PMID- 22097349 TI - [Overview in establishing animal models against ischemic cerebrocardiac disease and thinking about efficacy evaluation of traditional Chinese medicine]. AB - In order to explore the pathogenesis of ischemic cerebrovascular disease, drug screening, efficacy evaluation and treatment plan optimization, many kinds of animal models against ischemic cerrebrocardiac were established with operation successively in recent years. According to the characteristic of traditional Chinese medicine, it's a question to choose the appropriate animal model for drug screening and efficacy evaluation, and to combine the cerebral ischemia of animal models with clinical disease research closely. The stability and reliability of animal models and the efficacy of drugs in clinical should be considered in order to provide effective drug screening evaluation research tools. PMID- 22097350 TI - [Discussion on forming pattern of dao-di herbs Ligusticum chuanxiong]. AB - As a famous-region Dao-di Herbs, Ligusticum chuanxiong which mainly grows in the west of the upper reaches of Jinma River in Dujiangyan for a long time. In recent years, the history, species and origin of L. chuanxiong were researched by many scholars. However, the forming pattern of Dao-di herbs of L. chuanxiong has not been reported systematically. Basing on the general principles of the formation of Dao-di herbs, it can be concluded that the forming pattern of L. chuanxiong is the type of two determinants, which are combined both unique ecological environment of genuine regions and advanced cultivation techniques. PMID- 22097351 TI - [Herbal textual research on origin and development of chuanxiong]. AB - OBJECTIVE: To clarify the origin and development of Xiongqiong with medicinal literatures. METHOD: Medical literatures of past dynasties were analysed combined with the modern material. RESULT: There were two main origins of Xiongqiong in ancient times: eastern origin and western origin. It evolved into Chuanxiong and Xixiong because of cultivating in the western origin after Tang dynasty. The earliest original plant of Xiongqiong was Ligusticum sinense. Actually, Xixiong was the cultivation product of L. sinense. And L. chuanxiong was likely to be a gardening breed due to long-term cultivation of L. sinense. CONCLUSION: Xixiong is used as Xiongqiong in ancient times, but now it is used as Ligustici Rhizoma et Radix. Therefore, we need to find out the relationship between L. chuanxiong and L. sinense through modern research, and determine which Chinese herb is L. sinense classifies. PMID- 22097352 TI - [Effects of elevated CO2 concentration and nitrogen deposition on the biomass accumulation and allocation in south subtropical main native tree species and their mixed communities]. AB - A 5-year experiment was conducted to study the effects of simulated elevated CO2 concentration, nitrogen deposition, and their combination on the biomass accumulation and allocation in five south subtropical native tree species Schima superba, Ormosia pinnata, Acmena acuminatissima, Syzygium hancei, and Castanopsis hystrix and their mixed communities. The test tree species had different responses in their biomass accumulation and allocation to the elevated CO2 concentration and nitrogen deposition. Elevated CO2 concentration and nitrogen deposition increased the biomass of legume species by 49.3% and 71.0%, respectively, and promoted the biomass accumulation in sun species. Nitrogen deposition increased the biomass of shade-preference species significantly, but elevated CO2 concentration was in adverse. Elevated CO2 concentration inhibited the biomass allocation in the belowground part of sun species but promoted the biomass allocation in the belowground part of shade-preference species. Elevated CO2 concentration, nitrogen deposition, and their interaction all promoted the biomass accumulation in mixed communities. Elevated CO2 concentration increased the biomass accumulation in the belowground part of the communities, while nitrogen deposition increased the biomass accumulation in the aboveground part. Under the background of global climate change, Ormosia pinnata and Castanopsis hystrix tended to be the appropriate species for carbon fixation in south subtropical area. PMID- 22097353 TI - [Effects of aboveground and belowground competition between grass and tree on elm seedlings growth in Horqin Sandy Land]. AB - Elm sparse woodland steppe plays an important role in vegetation restoration and landscape protection in Horqin Sandy Land. In this paper, a two-factor and two level field experiment was conducted to explore the effects of aboveground and belowground competition between grass and tree on the growth of elm seedlings in the Sandy Land. Five aspects were considered, i.e., seedling biomass, belowground biomass/aboveground biomass, stem height, ratio of root to stem, and leaf number. For the one-year-old elm seedlings, their biomass showed a trend of no competition > aboveground competition > full competition > belowground competition, belowground biomass / aboveground biomass showed a trend of belowground competition > full competition > no competition > aboveground competition, stem height showed a trend of aboveground competition > no competition > full competition > belowground competition, root/stem ratio showed a trend of belowground competition > full competition > no competition > aboveground competition, and leaf number showed a trend of aboveground competition > no competition > belowground competition > full competition. Belowground competition had significant effects on the growth of one-year-old elm seedlings, while aboveground competition did not have. Neither belowground competition nor aboveground competition had significant effects on the growth of two-year-old elm seedlings. It was suggested that in Horqin Sandy Land, grass affected the growth of elm seedlings mainly via below-ground competition, but the belowground competition didn' t affect the resource allocation of elm seedlings. With the age increase of elm seedlings, the effects of grass competition on the growth of elm seedlings became weaker. PMID- 22097354 TI - [Spatial heterogeneity of plant community species diversity in Ejina Oasis at the lower reaches of Heihe River]. AB - By the method of geostatistics, this paper studied the spatial heterogeneity of plant community species diversity in Ejina Oasis at the lower reaches of Heihe River. In the study area, the Margalef richness index (Ma), Simpson diversity index (Ds), Shannon diversity index (H') and Pielou evenness index (J') were in normal distribution, and the coefficient of variation (CV) ranged from 55.8% to 67.8%, suggesting a moderate variability. The Ma and H' were accorded with exponential models, and the Ds and J' were accorded with spherical models. The H' had the highest extent of spatial variation, followed by Ma, J' and Ds. Within the variable range, the structural factors in the spatial variation of Ma, Ds, H', and J' were dominant, ranging from 81.1% to 93.0%. The indices changed obviously parallel to the river, with significantly high values near Dalaihubu Town (42 degrees N, 101 degrees E), and obviously low values within the strips 100 degrees-101 degrees E and 102 degrees-102 degrees 30' E, mainly including east and west Gobi and the hinterland of Badain Jaran Desert. PMID- 22097355 TI - [Effects of simulated acid rain on water physiological characteristics of Myrica rubra seedlings]. AB - Taking the seedlings of typical subtropical economic tree species Myrica rubra in Zhejiang Province as test materials, a pot experiment was conducted to study their water physiological characteristics under effects of simulated acid rain (pH 2.5 and pH 4.0), with water (pH 5.6) as the control. Season, year, and acid rain all had significant effects on the photosynthetic rate (Pn). Among the treatments, the Pn had a greater difference in summer than in spring and autumn, and was higher in treatment acid rain (pH 4.0). Season, year, acid rain, and the interactions of season and year and of the three factors had significant effects on the stomata conductance (Gs), and also, the Gs had a greater difference among the treatments in summer than in spring and autumn. Acid rain had inhibitory effect on Gs. Season, year, acid rain, and the interactions of season and year and of season and acid rain affected the transpiration rate (Tr) significantly. Same as Pn and Gs, the Tr had a greater difference among the treatments in summer than in spring and autumn. Acid rain (pH 2.5) had the strongest inhibitory effect on Tr. Acid rain and the interactions of season and year and of season and acid rain had significant effects on the water use efficiency (WUE), and acid rain (pH 2.5) had definitely positive effect on the WUE. PMID- 22097356 TI - [Characteristics of stemflow for typical alpine shrubs in Qilian Mountain]. AB - Taking the typical alpine shrubs Potentilla fruticosa, Salix cupularis, Hippophae rhamnoides, and Caragana jubata in Qilian Mountain as test objects, a field investigation from June 1 to October 31, 2010 was conducted on the variation characteristics of the shrub stemflow, and analyzed the affecting effects of rainfall intensity and canopy structure morphology. The stemflow generated when the rainfall in early period was 2.1 mm, with an average of 3.4%, 3.2%, 8.0%, and 4.2% of the gross rainfall for P. fruticosa, S. cupularis, H. rhamnoides, and C. jubata, respectively. There was a significant positive linear correlation between the stemflow and rainfall intensity. With increasing rainfall, the stemflow percentage showed a trend of increase-decrease-increase. Stemflow played an important role in supplying water to the shrub rhizosphere, and the average funneling ratio was 59, 30, 110, and 49 for P. fruticosa, S. cupularis, H. rhamnoides, and C. jubata, respectively. The stemflow percentage had a significant exponential relationship with the maximum rain intensity in 10 minutes (I10). When the I10 was more than 6.0 mm x h(-1), the stemflow of H. rhamnoides and C. jubata showed a persistently increasing trend, while that of P. fruticosa and S. cupularis tended to be stable. Canopy structure morphology had complicated effects on the stemflow. In the same rainfall intensities, the height and crown projection area of the shrubs were the important factors affecting the generation of stemflow. PMID- 22097357 TI - [Age structures of Spodiopogon sibiricus populations on weedy meadow and elm woodland in Songnen Plain, northeast China]. AB - In 2003 and 2006, investigations were made on the age structures of Spodiopogon sibiricus populations as well as the matter productivities and vegetative reproduction capacities of different age-class modules of the populations on the weedy meadow and elm woodland in Songnen Plain of northeast China. At the two habitats, the tillers of S. sibiricus all consisted of 2-3 age classes, and the rhizomes all composed of 4 age classes. Both the tillers and the rhizomes had the greatest proportion of 1- or 2-year-old, and the age structures were of expansive or stable. The 1- or 2-year-old tiller-node buds were dominant, and the rhizome topmost buds occupied 29.4%-45.0%, being of significance to the population regeneration in the next year. The 1- or 2-year-old modules of the tillers and rhizomes had the highest matter productivity and vegetative reproduction capacity, and the rhizomes had higher vegetative reproduction capacity than the tiller-nodes. PMID- 22097358 TI - [Effects of exogenous lead on the growth and lead accumulation characteristics of roadside dominant herbaceous plants in Shanxi Province]. AB - A greenhouse pot experiment was conducted to study the effects of different concentration (0, 500, 1000, 1500 mg x kg(-1)) lead (Pb) on the growth and Pb absorption and accumulation of 14 roadside dominant herbaceous plants in Shanxi Province. With increasing Pb concentration in the pot, Amaranthus retroflexus and Sorghum bicolor x S. sudanese appeared obviously toxic symptoms, while the other 12 test plants had higher Pb tolerance, with no significant decrease in their plant height and biomass, compared with control. Chenopodium album and Psathyrostachys juncea had the lowest Pb content (averaged 12.70 and 11.33 mg Pb x kg(-1), respectively) in their aboveground part and the lowest Pb ratio (0.12 and 0.10, respectively) of aboveground part / root, being the potential low Pb accumulation plants and able to be used for the vegetation restoration of Pb polluted soil. Red leaf A. tricolor and green leaf A. tricolor in treatment 1500 mg Pb x kg(-1) had the highest Pb accumulation (53.37 and 45.29 mg Pb per 100 plants, respectively) in their aboveground parts, being able to be chosen as the pioneer plants for the remediation of Pb-polluted soil. PMID- 22097359 TI - [Impacts of salt stress on the growth and physiological characteristics of Rosa rugosa]. AB - Taking 1-year-old cuttings of a wild type and three cultivars of Rosa rugosa as test materials, this paper studied their biomass, photosynthesis, osmotic adjustment substance contents, root activity, and ion contents under the stress of different concentration NaCl. Salt stress inhibited the growth of the cuttings, and root was more sensitive than shoot. Under salt stress, wild rose had significantly higher contents of free proline and soluble sugar than the cultivars, and the contents of free proline and soluble sugar in cultivar 'Ziyan' were higher than those in cultivars 'Zhongke 2' and 'Purple Branch'. Compared with rose cultivars, the wild rose under salt stress had smaller changes in its photosynthetic characteristics and root activity. It was suggested that wild rose had a higher resistance to salt stress than the cultivars, and cultivar 'Ziyan' had a higher resistance than 'Purple Branch' and 'Zhongke 2'. All the test indices could be used as the indicators of R. rugosa salt-tolerance. PMID- 22097360 TI - [Soil nutrient status of pure birch and larch plantations based on their seedlings bioassay]. AB - One-year-old birch (Betula platyphylla) and larch (Larix olgensis) seedlings were respectively planted in pots with the soils taken from 35-year-old pure birch and larch plantations, and the seedlings growth, biomass increment, foliar nutrient content, and soil nutrient status were monitored, aimed to evaluate the fertility levels of the two soils and the possible interspecific interaction in mixed larch birch forest. Birch soil had significantly higher contents of total N and available N than larch soil, while larch soil had significantly higher contents of total P, available P, and total K than birch soil (P < 0.05). In the first growth season, the height and collar diameter growth and the biomass accumulation of birch seedlings growing on birch soil were 69%, 52%, and 65% (P < 0.05) higher than those growing on larch soil, and the larch seedlings also had 12%, 8%, and 37% gains of the indices, respectively. The foliar N concentration of both larch and birch seedlings growing on birch soil was higher than that on larch soil, while the foliar P concentration was higher when the seedlings were growing on larch soil than on birch soil. The birch soil had higher content of available N because of the higher litterfall, while the larch soil had greater available P because of the higher P mobilizing effect. It was predicted that in mixed birch larch forest, the complementary interaction of soil N and P could benefit the growth of the two tree species. PMID- 22097361 TI - [Effects of simulated nitrogen deposition on soil available nitrogen forms and their contents in typical temperate forest stands]. AB - An indoor experiment was conducted to study the effects of simulated nitrogen deposition on the soil available N in typical temperate forest stands. During the experiment period, nitrogen deposition increased the soil NH4+ -N, NO3- -N, and available N contents, as compared with the control, but the increments differed with stand types, soil layers, nitrogen treatment types, and treatment duration. Mixed forest soil had weaker responses in its available N contents to the nitrogen deposition than broad-leaved forest soil but stronger responses than artificially pure coniferous forest soil, and soil A horizon was more sensitive to nitrogen deposition than soil B horizon. Ammonium nitrogen deposition had larger effects on soil NH4+ -N content, nitrate nitrogen deposition had larger effects on soil NO3- -N content, while mixed ammonium and nitrate nitrogen deposition increased the contents of both soil NH4+ -N and soil NO3- -N, and the increments were higher than those of ammonium nitrogen deposition and nitrate nitrogen deposition, suggesting the additive effects of the mixed ammonium and nitrate nitrogen deposition on the forest soil available N. PMID- 22097362 TI - [Carbon storage, density, and distribution in forest ecosystems in Jilin Province of northeast China]. AB - By using forest resources inventory data and field investigation data, this paper studied the carbon storage, density, and distribution characteristics in forest ecosystems in Jilin Province of Northeast China. The total carbon storage in the forest ecosystems was 1827.293 Tg C, and the carbon storages in arbor layer, shrub-grass layer, litter layer, and soil were 439.152 Tg C, 5.195 Tg C, 45.600 Tg C, and 1330.466 Tg C, accounting for 24.1%, 0.3%, 2.5%, and 73.1% of the total, respectively. The carbon density in the forest ecosystems was 225.304 Mg C x hm(-2), with 54.352 Mg C x hm(-2) in arbor layer, 0.643 Mg C x hm(-2) in shrub grass layer, 5.644 Mg C x hm(-2) in litter layer, and 164.666 Mg C x hm(-2) in soil. Different types of the forest ecosystems had a carbon storage varied from 9.357 Tg C to 959.716 Tg C and a carbon density ranged from 180.648 Mg C * hm(-2) to 254.627 Mg C x hm(-2), with the highest values in soil and the lowest values in shrub-grass layer. Overall, the carbon storage and density in the forest ecosystems were greater in eastern mountainous area than in central and western plains. In the Province, middle-aged forests had a greater proportion than the forests in other age classes, and thereby, a proper management of the present forests could increase the carbon sequestration of the forest ecosystems. PMID- 22097363 TI - [Changes of China agricultural climate resources under the background of climate change. VIII. Change characteristics of heat resources during the growth period of double cropping rice in Jiangxi Province]. AB - Based on the observation data from the meteorological stations and agricultural experimental stations in Jiangxi Province, this paper studied the change trend of the growth period of double cropping rice in the province, and, by using the indices growing degree-days (GDD), cool degree-days (CDD), and heat degree-days (HDD), the change trends of the heat resources at each growth stage of the double cropping rice in 1981-2007 were analyzed. Under the background of climate warming, the mean air temperature, mean minimum air temperature, mean maximum air temperature during the growth period of the double cropping rice all had an increasing trend, leading to the shortening of double cropping rice growth season, with the most obvious decrease of vegetative growth phase and the prolonged reproductive growth phase. In the vegetative growth phase, the GDD and HDD increased, while the CDD decreased. In 1981-2007, the effective heat resources of double cropping rice in Jiangxi Province increased, low temperature risk reduced, while high temperature risk increased. The increment of the effective heat resources for double cropping rice was higher in northeast Jiangxi than in southwest Jiangxi, low temperature risk was higher in south Jiangxi than that in north Jiangxi, and high temperature risk was the highest in middle Jiangxi. PMID- 22097364 TI - [Effects of applying controlled-release fertilizer and its combination with urea on nitrous oxide emission during rice growth period]. AB - By the method of static chamber, a field experiment was conducted to study the effects of applying controlled-release fertilizer (CRF) and its combination with urea on the N2O emission during rice growth period. Four treatments, i.e., no fertilization (CK), urea (U), urea and CRF with a ratio of 3:7 (U+C), and CRF (C) were installed, and the N application rate in treatments U, U+C, and C was the same. Compared with treatment U, treatments U+C and C decreased the N2O emission during rice growth season by 40.4% and 59.6%, and decreased the emission at midseason aeration stage by 65.1% and 83.9%, respectively (P < 0.05). Compared with that in treatment C, the N2O emission in treatment U+C had a slight decrease, and decreased by 53.9% at midseason aeration stage. Applying CRF increased rice yield, and the increment in treatments C and U+C was 7.8% and 9.8%, respectively, as compared to treatment U. Applying CRF delayed the peak time of soil inorganic nitrogen concentration, resulting in the reduction of N2O emission at midseason aeration stage. During rice growth season, no significant correlation was observed between N2O flux and soil Eh or soil temperature. PMID- 22097365 TI - [Effects of nitrogen application and ridge film furrow planting on water use of winter wheat in dry land of south Shanxi]. AB - A 2-year (2008-2010) field experiment was conducted to study the effects of basal dressing nitrogen, topdressing nitrogen, and ridge film furrow planting on the 0 2 m soil moisture status and the grain yield and water use efficiency of winter wheat in rain-fed area of South Shanxi Province. In all treatments, the soil moisture status during winter wheat growth period had the same change trend, being increased steadily from pre-sowing to revival stage and decreased sharply from revival stage to heading stage, and then increased gradually till maturity stage. From revival stage to heading stage, the soil water consumption was the most. Increasing nitrogen basal application rate or topdressing nitrogen increased the soil water consumption, widened the soil moisture active layer, and deepened the relatively stable layer. Topdressing nitrogen increased grain yield significantly; ridge film furrow planting decreased soil water consumption obviously. The water use efficiency under ridge film furrow planting was 23.4% and 39.1% higher than that under conventional planting system in 2009 and 2010 (P < 0.01). The grain yield under ridge film furrow planting plus top-dressing nitrogen was 3643 kg x hm(-2), which was significantly higher than that under single ridge film furrow planting or topdressing nitrogen, displaying a preferable water-fertilizer coupling effect. PMID- 22097366 TI - [Salt tolerance evaluation of cotton (Gossypium hirsutum) at its germinating and seedling stages and selection of related indices]. AB - A sand culture experiment was conducted to study the salt tolerance of 13 cotton cultivars at their germinating and seedling stages under the stress of different concentration NaCl, and a cluster analysis was made on the salt tolerance, according to the subjection values of salt toxicity coefficients of multi-indices and the sum subjection value. It was observed that the appropriate concentration of NaCl for the evaluation of salt tolerance was 150 mmol x L(-1). The salt tolerance differed with cultivar and growth stage. Among the 13 cultivars, the CCRI-44 and CCRI-177 were steadily salt-tolerant at both germinating and seedling stages, the CCRI-103, Dexiamian 1, and NuCOTN 33B were steadily and moderately salt-tolerant, while the CCRI-102, Sumian 12, and Simian 3 were steadily salt sensitive. Germination rate, germination potential, germination index, vigor index, and fresh mass could be served as the indicators to evaluate the salt tolerance of the cultivars at germinating stage, while plant height, leaf expansion rate, shoot dry mass, root dry mass, root vigor, and net photosynthetic rate could be applied to assess the salt tolerance at seedling stage. PMID- 22097367 TI - [Effects of solar greenhouse vegetable cultivation on soil physical quality]. AB - Taking the solar greenhouse heavy loam soil having been planted vegetables for different years at Yunyang Town in Jingyang County of Shaanxi Province as test objects, and with the uncovered vegetable soil adjacent to the greenhouse as the control, this paper studied the effects of solar greenhouse vegetable cultivation on soil physical quality. Solar greenhouse vegetable cultivation had greater effects on the bulk density of 0-30 cm soil layer (an increase in 0-10 cm soil layer and a decrease in 10-30 cm soil layer), but little effects on that of 30-40 cm soil layer. In 0-40 cm solar greenhouse soil profile, the contents of < 0.01 mm physical clay and < 0.001 mm clay were lower in upper layer than in deeper layer, indicating their downward movement, and this phenomenon was more obvious with increasing year of solar greenhouse vegetable cultivation. Within the first 5 years of solar greenhouse vegetable cultivation, soil field water capacity decreased significantly, with a decrement of 13.8%, but remained relatively stable after then. PMID- 22097368 TI - [Effects of sunken depth of energy-saving solar greenhouse on the diurnal variation and spatial distribution of environmental factors in the greenhouse]. AB - Taking the energy-saving solar greenhouses with the same infrastructure but different sunken depths (0, 0.5, 1.0, and 1.5 m) in Tai' an of Shandong Province as test objects, this paper analyzed the intercepted amount of direct solar radiation energy, and studied the diurnal variation and spatial distribution patterns of environmental factors in the greenhouses on winter solstice (December 20-24, 2009) and summer solstice (June 19-23, 2010). With the increase of sunken depth, the shadow areas in the greenhouses caused by sunken profiles increased gradually, the direct solar radiation energy into the interior of the greenhouses shifted from south to north, and the ratio of ground radiation to back wall radiation decreased gradually. Within the range of 0-1.0 m sunken depth, the air temperature and soil temperature in the greenhouses increased significantly with increasing sunken depth; but when the sunken depth was 1.5 m, the warming effect declined significantly, and the deviation of the lowest soil temperature increased. The deeper the sunken depth, the lower the light intensity and the higher the relative humidity in the greenhouses were. In considering of both lighting and heat preservation, the appropriate sunken depth of energy-saving sunlight greenhouses with a span of 10 m in Tai' an region should be less than 1.0 m. PMID- 22097369 TI - [Dynamic changes of surface soil organic carbon and light-fraction organic carbon after mobile dune afforestation with Mongolian pine in Horqin Sandy Land]. AB - This paper studied the dynamic changes of surface (0-15 cm) soil organic carbon (SOC) and light-fraction organic carbon (LFOC) in 25- and 35-year-old sand-fixing Mongolian pine (Pinus sylvestris var. mongolica) plantations in Horqin Sandy Land, with a mobile dune as a comparison site. After the afforestation on mobile dune, the content of coarse sand in soil decreased, while that of fine sand and clay-silt increased significantly. The SOC and LFOC contents also increased significantly, but tended to decrease with increasing soil depth. Afforestation increased the storages of SOC and LFOC in surface soil, and the increment increased with plantation age. In the two plantations, the increment of surface soil LFOC storage was much higher than that of SOC storage, suggesting that mobile dune afforestation had a larger effect on surface soil LFOC than on SOC. PMID- 22097370 TI - [Crop-soil nitrogen cycling and soil organic carbon balance in black soil zone of Jilin Province based on DSSAT model]. AB - By using the CERES-Maize crop model and Century soil model in Decision Support System of Agrotechnology Transfer (DSSAT) model, this paper studied the effects of crop management parameters, fertilizer N application rate, soil initial N supply, and crop residue application on the maize growth, crop-soil N cycling, and soil organic C and N ecological balance in black soil (Mollisol) zone of Jilin Province, Northeast China. Taking 12,000-15,000 kg x hm(-2) as the target yield of maize, the optimum N application rate was 200-240 kg N x hm(-2). Under this fertilization, the aboveground part N uptake was 250-290 kg N x hm(-2), among which, 120-140 kg N x hm(-2) came from soil, and 130-150 kg N x hm(-2) came from fertilizer. Increasing the N application rate (250-420 kg N x hm(-2)) induced an obvious increase of soil residual N (63-183 kg x hm(-2)); delaying the N topdressing date also induced the increase of the residual N. When the crop residue application exceeded 6000 kg x hm(-2), the soil active organic C and N could maintain the supply/demand balance during maize growth season. To achieve the target maize yield and maintain the ecological balance of soil organic C and N in black soil zone of Jilin Province, the chemical N application rate would be controlled in the range of 200-240 kg N x hm(-2), topdressing N should be at proper date, and the application amount of crop residue would be up to 6000 kg x hm(-2). PMID- 22097371 TI - [Vulnerability assessment of eco-environment in Yimeng mountainous area of Shandong Province based on SRP conceptual model]. AB - Based on the ecological sensitivity-resilience-pressure (SRP) conceptual model, and selecting 13 indices including landscape diversity index, soil erosion, and elevation, etc. , the vulnerability of the eco-environment in Yimeng mountainous area of Shandong Province was assessed under the support of GIS and by using principal component analysis and hierarchy analytical method. According to the eco-environmental vulnerability index (EVI) values, the eco-environment vulnerability of study area was classified into 5 levels, i.e., slight (<1.8), light (1.8-2.8), moderate (2.8-3.5), heavy (3.5-4.0), and extreme vulnerability (>4.0). In the study area, moderately vulnerable area occupied 43.3% of the total, while the slightly, lightly, heavily, and extremely vulnerable areas occupied 6.1%, 33.8%, 15.9%, and 0.9%, respectively. The heavily and extremely vulnerable areas mainly located in the topographically complicated hilly area or the hill-plain ecotone with frequent human activities. PMID- 22097372 TI - [Spatiotemporal dynamics of land cover in northern Tibetan Plateau with responses to climate change]. AB - By using the 2001-2008 MOMS land cover products (MCDl2Ql) and based on the modified classification scheme embodied the characteristics of land cover in northern Tibetan Plateau, the annual land cover type maps of the Plateau were drawn, with the dynamic changes of each land cover type analyzed by classification statistics, dynamic transfer matrix, and landscape pattern indices. In 2001-2008, due to the acceleration of global climate warming, the areas of glacier and snow-covered land in the Plateau decreased rapidly, and the melted snow water gathered into low-lying valley or basin, making the lake level raised and the lake area enlarged. Some permanent wetlands were formed because of partially submersed grassland. The vegetation cover did not show any evident meliorated or degraded trend. From 2001 to 2004, as the climate became warmer and wetter, the spatial distribution of desert began to shrink, and the proportions of sparse grassland and grassland increased. From 2006 to 2007, due to the warmer and drier climate, the desert bare land increased, and the sparse grassland decreased. From 2001 to 2008, both the landscape fragmentation degree and the land cover heterogeneity decreased, and the differences in the proportions of all land cover types somewhat enlarged. PMID- 22097373 TI - [Simulation of vegetation landscape in Pingtan Island based on BP neural network model]. AB - Taking GIS as technical platform and by using Matlab 7.0, the vegetation landscape in Pingtan Island was cut with 2 km x 2 km grid graph. The data of 50 quadrats were obtained. Forty-four of the 50 quadrates were used for model training, and the rest 6 were used for model checking. Fractal dimension, Shannon diversity index, and contagion index were selected as output data of the model, and the number of residential quarter, wind speed, and the distance from the coast were chosen as affecting factors. A BP neural network model of vegetation landscape in Pingtan Island was established, and was checked by error test. The results demonstrated that the major factors affecting the vegetation landscape spatial pattern and diversity in Pingtan Island were wind speed and the distance from the coast, and anthropogenic factors had greater effects on the spatial connection of vegetation landscape. The fitted results of the relationships between vegetation landscape and environmental and anthropogenic factors were basically accorded with the truth. The average error was 7.4%, and the minimum error was 0.2%, indicating that the model could be applied to quantitatively predict and simulate the vegetation landscape in Pingtan Island. PMID- 22097374 TI - [Priority areas for biodiversity conservation in Hainan Island: evaluation and systematic conservation planning]. AB - A total of 140 endangered species in Hainan Island were selected as indicator species, and their spatial distribution patterns were analyzed by using mechanism habitat model. Based on the iterative operation with systematic conservation planning tool MARXAN, the priority areas of these species were identified and evaluated. The priority areas had an area of 5383.7 km2, accounting for 15.6% of the total land area of the Island, and mainly distributed in some forest regions (Yinggeling, Jianfengling and Wuzhishan) and in northern part water source regions. In the priority areas, the conservation proportion of 11 1st grade indicator species habitats occupied at least 65% of all the habitats. Through the gap analysis of priority areas and current nature reserves, it was suggested that an expansion of Jianfengling, Yinggeling-Limushan, and Wuzhishan-Diaoluoshan nature reserves and the establishment of Baolonglinchang-Linbiling-Fuwanling protection system should be made, and the protection areas for water source conservation and endangered species should be established in the northern part of the Island. PMID- 22097375 TI - [Applications of habitat equivalency analysis in ecological damage assessment of oil spill incident]. AB - Habitat equivalency analysis (HEA) is one of the methods commonly used by U.S. National Oceanic and Atmospheric Administration in natural resources damage assessment, but rarely applied in China. Based on the theory of HEA and the assessment practices of domestic oil spill incidents, a modification on the HEA was made in this paper, and applied to calculate the habitat value in oil spill incidents. According to the data collected from an oil spill incident in China, the modified HEA was applied in a case study to scale the compensatory restoration. By introducing the ecological service equivalent factor to transfer various habitats, it was achieved to value of the injured habitats in ecological damage assessment of oil spill incident. PMID- 22097376 TI - [Characteristics of non-point source pollution in Tiaoxi watershed and related affecting factors]. AB - By using soil and water assessment tool (SWAT) model, this paper simulated the surface runoff intensity and the export loadings of sediment particulates and nutrients via non-point source hydrological pathway in Tiaoxi watershed, and integrated with the simulation results, analyzed the temporal and spatial distribution characteristics of non-point source pollution in the watershed in 2008. In the study area, the per unit area non-point source pollution was stronger in northern region than in southern region and in eastern region than in western region, and the weakest in central region. Among the land utilization types, farmland had the biggest contribution to the sediment loading. There were significantly positive correlations between the loadings of surface runoff and associated sediment particulates and the rainfall intensity. The export loadings of nutrients through surface runoff were higher in rainy season (from June to September) than in dry season (from December to next March), and there existed significant correlations between the surface runoff loadings of sediment particulates, organic nitrogen, and nitrate and the average gradient of lands. PMID- 22097377 TI - [Spatial pattern and its variation of Cnaphalocrocis medinalis larvae and Ummeliata insecticeps under paddy rice cropping neighboring with vegetables or corn]. AB - Geostatistical methods were adopted to characterize the spatial pattern and its variation of Cnaphalocrocis medinalis larvae (Lepidoptera: Crambidae) and Ummeliata insecticeps (Araneida: Linyphiidae) in the habitats of paddy rice neighboring with white melon, tomato, or corn. In the rice growth period, C. medinalis larvae and U. insecticeps presented aggregative distribution, with the spatial range varied from 1.91 to 182.57 m and from 3.70 to 9.70 m, respectively. Isoline map showed that the density of U. insecticeps was spatially and temporally identical with that of C. medinalis larvae, suggesting that U. insecticeps had strong pursuing and control effects on C. medinalis larvae. Among the test neighboring patterns, paddy rice neighboring with white melon had the best performance of U. insecticeps. PMID- 22097378 TI - [Effects of Bt corn straw insecticidal proteins on enzyme activities of Eisenia fetida]. AB - Bacillus thuringiensis (Bt) proteins released from Bt corn can enter soil ecosystem via returning straw into field, root exudation, and pollen fluttering down. In this study, the straws of Bt corn and its near-isogenic non-Bt line were added into soil with an application rate of 5% and 7.5% to breed Eisenia fetida, and the total protein content and the activities of acetylcholine esterase (AchE), glutathione peroxidase (GSH-PX), catalase (CAT), and superoxide dismutase (SOD) in E. fetida were determined after 7 and 14 days. Under the same application rate of the straws, the total protein content and GSH-PX activity of E. fetida decreased while the AchE, CAT, and SOD activities increased on the 14th day, compared with those on the 7th day. The Bt corn straw increased the SOD activity and decreased the AchE and GSH-PX activities, but had less effects on the total protein content and CAT activity, compared with non-Bt corn straw. All the results suggested that Bt corn straw had no inhibitory effect on E. fetida total protein but could inhibit the AchE and GSH-PX activities, and could not induce CAT activity but induce SOD activity within a short time. PMID- 22097379 TI - [Colonization and disease control and fruit preservation functions of endophytic bacterial strains in lychee]. AB - By spraying the GFP-marked endophytic bacterial strains BS-2-gfp and TB2-gfp, this paper studied their colonization in lychee organs and the functions of the strains in disease control and fruit preservation. The BS-2-gfp and TB2-gfp could colonize and propagate in lychee leaves, flowers, un-matured fruits, and matured fruits, and transfer from the flowers to un-matured fruits. The colonization of BS-2-gfp and TB2-gfp in lychee leaves varied with season and growth stage, being larger in quantity and longer in duration in spring than in autumn. The colonization quantity and duration of the strains also differed in other organs. Both the BS-2-gfp and the TB2-gfp could be isolated and recovered from lychee leaves after 37 d inoculation, the BS-2-gfp could not be isolated from the flowers after inoculation for 10 d, and the BS-2-gfp and TB2-gfp had the largest colonization quantity in matured fruits. The colonization quantity of TB2-gfp in lychee pericarp reached to the maximum (1.90 x 10(6) CFU x g(-1) FM) when the disease index of litchi downy blight had a sharp increase, and, compared with BS 2-gfp, the TB2-gfp had better fruit preservation efficiency, and its colonization quantity in lychee pericarp was also higher. It was suggested that there was a positive correlation between the colonization quantity of test bacterial strains in lychee pericarp and the disease control and fruit preservation effect. PMID- 22097380 TI - [Resistance realized heritability and risk assessment of Panonychus citri to avermectin and fenpropathrin]. AB - On the basis of resistance breeding and selection in laboratory, and by using the threshold trait analysis in quantitative genetics, this paper studied the realized resistance heritability of Panonychus citri (McGregor) collected from Beibei of Chongqing to avermectin and fenpropathrin, and predicted the resistance risk of P. citri to these two acaricides. After 11- and 16-generations of selection with avermectin and fenpropathrin, the resistance of P. citri to the two acaricides increased by 3.8- and 29.9-fold, and the realized resistance heritability was 0.0475 and 0.1544, respectively. Under laboratory condition, to develop a 10-fold increase of resistance required 12-26 generations of selection for avermectin, and 7-16 generations of selection for fenpropathrin under the selection pressure of 50%-90% mortality for each generation. Under field condition, it would require more generations to develop the same resistance level. Comparing with bioacaricide avermectin, pyrethroid fenpropathrin had obviously higher resistance risk to P. citri. The results provided references for the resistance management of P. citri to acaricides. PMID- 22097381 TI - [Responses of ground arthropod functional groups to the enclosure of grazing grassland in desert steppe]. AB - With the support of the National Resources Monitoring Station in Yanchi County of Ningxia, an investigation was conducted on the ground arthropods, vegetations, and soil properties in the enclosed and un-enclosed grazing grassland in desert steppe. In the meantime, the functional groups of ground arthropods were classified according to their feeding habits. The ground arthropods in the desert steppe could be classified into four functional groups, i.e., predatory, phytophagous, saprophagous, and omnivorous, among which, predatory and phytophagous groups were dominant in quantity, and phytophagous and saprophagous groups were predominant in biomass, implying that the ground arthropod in desert steppe was mainly characterized by phytophagous arthropods. Enclosure increased the individual and group number of predatory, phytophagous, and omnivorous arthropods as well as the biomass of predatory and omnivorous arthropods, and enhanced the biodiversity of predatory and phytophagous arthropods, which was closely correlated with the vegetation recovery and soil environment improvement, and demonstrated that the enclosure of grazing grassland increased the diversity and complexity of ground arthropod functional groups in desert steppe. Nevertheless, the individual number and biomass of saprophagous arthropods decreased after the enclosure, reflecting the dependence of these arthropods on grazing grassland. PMID- 22097382 TI - [Effects of artificial reef construction to marine ecosystem services value: a case of Yang-Meikeng artificial reef region in Shenzhen]. AB - Based on the researches and statistic data of Yangmeikeng artificial reef region in Shenzhen in 2008 and by the method of ecosystem services value, this paper analyzed the effects of artificial reef construction in the region on the marine ecosystem services. After the artificial reef construction, the tourism service value in the region decreased from 87% to 42%, food supply service value increased from 7% to 27%, and the services value of raw material supply, climatic regulation, air quality regulation, water quality regulation, harmful organism and disease regulation, and knowledge expansion had a slight increase, as compared to the surrounding coastal areas. The total services value per unit area of Yangmeikeng artificial reef region in 2008 was 1714.7 x 10(4) yuan x km(-2), far higher than the mean services value of coastal marine ecosystem in the surrounding areas of Shenzhen and in the world. Artificial reef construction affected and altered the structure of regional marine ecosystem services value, and improved the regional ecosystem services value, being of significance for the rational exploitation and utilization of marine resources and the successful recovery of damaged marine eco-environment and fish resources. Utilizing the method of ecosystem services value to evaluate artificial reef construction region could better elucidate the benefits of artificial reef construction, effectively promote the development of our artificial reef construction, and improve the management of marine ecosystem. PMID- 22097383 TI - [Sexual reproductive allocation of Sargassum thunbergii at Taiping Cape of Yellow Sea]. AB - This paper studied the dynamics of reproductive allocation (RA) of Sargassum thunbergii during its sexual reproductive season and the related environmental factors at the Taiping Cape of Yellow Sea. The sexual reproduction of S. thunbergii initiated in early June, peaked in mid July when the sea water temperature was about 22 degrees C (the mean proportion of biomass allocated to reproductive organs on July 19 was 76.7%), and ended in late August. The RA had a significant linear correlation with the average length of thallus branches (r = 0.855, P < 0.01). The thalli with a length less than 10 cm showed a lower RA in the whole sexual reproductive season, while the thalli longer than 10 cm had a RA up to averagely 70.0% at the peak maturing stage. UNIANOVA analysis showed that both tidal level and wave strength had significant effects on the RA of S. thunbergii (tidal level: F = 175.62, P < 0.01; wave strength: F = 95.35, P < 0.01), and there was a significant interaction between tidal level and wave strength (F = 9.14, P < 0.05). The sizes of the effects were in the order of tidal level > wave strength > tidal level x wave strength. PMID- 22097384 TI - [Secondary productivity of macrobenthos in rocky intertidal zone of Yushan Islands, Zhejiang Province]. AB - In order to understand the current status of macrobenthos in intertidal zone of Yushan Islands, macrobenthos samples were collected from 5 sections in the intertidal zone in four seasons from March 2009 to January 2010, with the density, biomass, secondary productivity, and P/B value of the macrobenthos investigated by using Brey's empirical formula. The mean density of the marobenthos was 1419.5 ind x m(-2), mean biomass in ash free dry mass (AFDM) was 565.53 g x m(-2), mean annual secondary productivity was 285.58 g x m(-2) x a(-1) (AFDM), and mean annual P/B value was 0.51. The secondary productivity was mainly affected by mollusca and gastropda, with five critical species Septifer virgatus, Modiolus modiolus, Serpulorbis imbricata, Tetraclita japonica, and T. squamosa contributed 84.0% of the total. The P/B value in the study area was lower than that in other sea areas, showing that the generation turnover rate of the macrobenthos in the intertidal zone of Yushan Islands was slower, and the community structure was more stable. PMID- 22097385 TI - [Impacts of ultraviolet irradiation on the sperm motility and longevity of Acipenser baerii]. AB - This paper studied the impacts of different dose ultraviolet irradiation (254 nm, UVC) on the sperm motility and longevity of Acipenser baerii. Ultraviolet irradiation had significant impacts on the sperm motility, its fast motion time, and longevity. With the increasing dose of ultraviolet irradiation, the sperm motility decreased rapidly first, increased rapidly then, and decreased rapidly again. The sperm fast motion time had the similar variation trend as the sperm motility, but the sperm longevity kept decreasing with increasing dose of ultraviolet irradiation. When the ultraviolet irradiation dose increased to 288 mJ x cm(-2), the sperm fast motion disappeared; when the ultraviolet irradiation dose increased up to 324 mJ x cm(-2), the sperm had no motility and died. According to the "Hertwig effect", the optimum ultraviolet irradiation dose for inactivating A. baerii sperm was 216 mJ x cm(-2). PMID- 22097386 TI - [Edge effect and its impacts on forest ecosystem: a review]. AB - Edge effect is an important concept in ecology and biological conservation, playing an important role in the study of ecological processes such as energy and material flow at ecosystem scale and landscape scale. This paper expatiated the connotation, features, quantitative evaluation (basis of quantitative analysis, strength, impact zone, and models, etc.), and applied aspects of edge effect, summarized the impacts of edge effect on forest ecosystem, analyzed the deficiencies in the study of edge effect, and prospected related research directions, aimed to provide references for forest and protected area management. PMID- 22097387 TI - [Effects of seasonal snow cover on soil nitrogen transformation in alpine ecosystem: a review]. AB - Seasonal snow cover has pronounced effects on the soil nitrogen concentration and transformation in alpine ecosystem. Snowfall is an important form of nitrogen deposition, which directly affects the content of soil available nitrogen. Different depths and different duration of snow cover caused by snowfall may lead the heterogeneity of abiotic factors (soil temperature and moisture) and biotic factors (soil microbes, alpine plants, and alpine animals), and further, produce complicated effects on the mineralization and immobilization of soil nitrogen. This paper introduced in emphasis the inherent mechanisms of soil nitrogen mineralization and leaching under the effects of frequent freeze-thaw events during the durative melting of snow cover, and summarized the main research results of field in situ experiments about the effects of seasonal snow cover on soil nitrogen in alpine ecosystem based on the possible changes in snow cover in the future. Some suggestions with regard to the effects of seasonal snow cover on soil nitrogen were put forward. PMID- 22097388 TI - [Technical strategies in the research of plant salt-responsive proteomics: a review]. AB - Soil salinization is one of the key factors limiting plant growth and distribution. To explore plant molecular salt-responsive mechanisms is the basis of enhancing plant salt tolerance in virtue of molecular biological techniques, and also, the hotspot of plant physiology and molecular ecology. High throughput proteomics approaches include two-dimensional electrophoresis (2-DE), blue native/SDS-PAGE (BN/SDS-PAGE), two-dimensional fluorescence difference gel electrophoresis (2D DIGE), liquid chromatography (LC), and various mass spectrometry (MS) techniques, being widely applied in the research of plant salt response and supplied important information for understanding plant molecular salt-tolerant mechanisms. In this paper, a review was made on the technical strategies applied in the research of plant salt-responsive proteomics. PMID- 22097389 TI - [Otolith microchemistry of tuna species: research progress]. AB - Microchemistry analysis of trace elements and isotopes in fishes' calcified substances is an emerging approach to analyze the population structure, life history, and migration environmental history of fishes. With the increasing improvement of the researches and applications of otolith microchemistry, this approach has been a good tool for studying the ecology of tuna species. Currently, the research contents of tuna species' otolith microchemistry mainly include trace elements and isotopes, and the former is the emphasis and hotspot in applied research, playing a vital role in the researches of population partitioning, natal origin, migration environmental history, and life history of tuna species, especially bluefin tuna. However, most of the researches are focusing on the variation of otolith's Sr/Ca ratio, and there is no final conclusion on the relationships between the fractionation of isotopes C and O in otolith and the temperature. For the sake of exploiting the huge value of otolith microchemistry, it would be necessary to strengthen the researches on the deposition mechanisms of trace elements in otolith, and to analyze the spatio temporal variations of various trace elements in otolith by comprehensive research methods. PMID- 22097390 TI - [Bio-treatment of grease wastewater: research progress]. AB - In conventional wastewater bio-treatment, little attention has been paid on the bio-degradation of grease, causing low efficiency in the process, and thereby, further study should be made on the development and application of related mature and effective bio-treatment techniques. This paper summarized the pathways and mechanisms of grease bio-degradation in wastewater treatment, with the focus on the research progress in the functional microbes involved in lipid hydrolysis and long-chain fatty acid degradation, and briefly introduced a series of new treatment technologies based on the habitat differences of the functional microbes. The key breakthrough directions in the technological study of grease bio-degradation were prospected, expecting to provide theoretical guidance to the development of the related technologies. PMID- 22097391 TI - A new method for determining phospholipase D activity using the monomolecular film technique. AB - A versatile and continuous assay for phospholipase D (PL D) activity was developed using the monomolecular film technique. For this purpose, a two-step enzymatic reaction was used. First, PL D hydrolysis of stable 1,2-diacyl-sn glycero-3-phosphocholine (PC) films by PL D generated a stable 1,2-diacyl-sn glycero-3-phosphate (PA) film and water-soluble choline. Secondly, the latter acidic phospholipid, in contrast to the initial PC molecule, was further hydrolysed under the action of porcine pancreatic lipase (PPL) in order to give rise to lysophosphatidic acid and fatty acid, which were rapidly desorbed from the interface. With this new procedure, it is possible to obtain continuous and accurate kinetic measurements of the PL D-catalyzed reaction with phospholipid monolayers as substrates. The PLD kinetics were linear with time and the velocities recorded were directly dependent upon the amount of PL D used. In a preliminary study, we investigated the effects of the surface pressure on the PL D activity. PMID- 22097392 TI - [Operative treatment of painful neuromas]. AB - 3-5% of patients with traumatic or iatrogenic peripheral nerve injury develop a painful neuroma, especially following trauma of small cutaneous sensory nerve branches. Neuroma pain is difficult to treat and often leads to loss of function and reduction of quality of life. Patients with a painful neuroma present with spontaneous electric, shooting or burning pain, allodynia, hyperalgesia and cold intolerance. The diagnosis is based on the medical history and physical examination, supplemented by Tinel's test and a diagnostic nerve blockade. Lasting pain relief is possible by means of surgical neuroma treatment performed by a plastic surgeon. Surgical treatment consists of repair or denervation of the nerve with relocation of the nerve stump in bone or muscle tissue or a vein. Referral of neuroma patients without delay to a plastic surgeon or multidisciplinary consultation is important, because the symptoms become increasingly difficult to treat over time. 3-5% of patients with traumatic or iatrogenic peripheral nerve injury develop a painful neuroma, especially following trauma of small cutaneous sensory nerve branches. Neuroma pain is difficult to treat and often leads to loss of function and reduction of quality of life. Patients with a painful neuroma present with spontaneous electric, shooting or burning pain, allodynia, hyperalgesia and cold intolerance. The diagnosis is based on the medical history and physical examination, supplemented by Tinel's test and a diagnostic nerve blockade. Lasting pain relief is possible by means of surgical neuroma treatment performed by a plastic surgeon. Surgical treatment consists of repair or denervation of the nerve with relocation of the nerve stump in bone or muscle tissue or a vein. Referral of neuroma patients without delay to a plastic surgeon or multidisciplinary consultation is important, because the symptoms become increasingly difficult to treat over time. PMID- 22097393 TI - State trends in premiums and deductibles, 2003-2010: the need for action to address rising costs. AB - Rapidly rising health insurance costs continue to strain the budgets of U.S. families and employers. This issue brief analyzes changes in private employer based health premiums and deductibles for all states from 2003 to 2010, and finds total premiums for family coverage increased 50 percent across states and employee annual share of premiums increased by 63 percent over these seven years. At the same time, per-person deductibles doubled in large, as well as small, firms. If premium trends continue at the rate prior to enactment of the Affordable Care Act, the average premium for family coverage will rise 72 percent by 2020, to nearly $24,000. Health reform offers the potential to reduce insurance cost growth while improving financial protections. If efforts succeed in slowing annual premium growth by 1 percentage point, by 2020 employers and families together would save $2,161 annually for family coverage, compared with projected premiums at historical rates of increase. PMID- 22097394 TI - Compared to Canadians, U.S. physicians spend nearly four times as much money interacting with payers. AB - KEY FINDINGS: (1) In Canadian office practices, physi-cians spent 2.2 hours per week interacting with payers, nurses spent 2.5 hours, and clerical staff spent 15.9 hours. In U.S. practices, physicians spent 3.4 hours per week interacting with payers, nurses spent 20.6 hours, and clerical staff spent 53.1 hours. (2) Canadian physician practices spent $22,205 per physician per year on interactions with health plans. U.S. physician practices spent $82,975 per physician per year. (3) U.S. physician practices spend $60,770 per physician per year more (approximately four times as much) than their Canadian counterparts. PMID- 22097395 TI - Children's exposure to secondhand smoke: nearly one million affected in California. AB - Despite the steady decline of smoking rates in California, over 200,000 children under age 12 live in homes where smoking is allowed, and another 742,000 live with an adult or adolescent smoker. Significant differences in children's exposure to tobacco smoke and risk of exposure are found by race/ethnicity, geographic regions within the state and by poverty level. African-American children were found to have a significantly higher rate of exposure than other racial and ethnic groups, while children in the Northern/Sierra and San Joaquin Valley regions were at the highest risk of exposure to secondhand smoke. Children living in lower-income households were also at higher risk. These findings can aid strategies to decrease children's exposure to tobacco smoke in the home through targeted public health messages and outreach to those enrolled in public programs. PMID- 22097396 TI - [Polite robots and shot necked monsters]. PMID- 22097397 TI - [Franz Muntefering attempts answers for the demographic change. Social democratic principles disturb a little. Munte discovers nursing]. PMID- 22097398 TI - [Violence on the unit: experts explain background and give practical advice. "Nurses experience aggression in a patient as a personal failure" (interview by Lex)]. PMID- 22097399 TI - [Robots in the nursing home. "It gives the impression of something pleasantly service-like"]. PMID- 22097400 TI - [The power of speech: how nurses positively influence nursing routine with communication. Using words to move the world]. PMID- 22097401 TI - [A memorandum for quality and safety of health care of tomorrow. Cooperation among health professions]. PMID- 22097402 TI - [How mothers experience the daily routine with their tracheotomized infants. "These short necked monsters are indeed life threatening"]. PMID- 22097403 TI - [Dying in homelessness. "It's nice that you come to me"!]. PMID- 22097404 TI - [Shared-housing arrangements for care dependent older persons. Support from family members and volunteers]. AB - Due to growing numbers of older care dependant persons shared-housing arrangements (SHA) were developed as a new approach, especially for those elderly People suffering from dementia. The involvement of family members and volunteers is a core component of the SHA concept. Besides the active involvement in meaningful activities, relatives also often act as legal representatives. Empirical data concerning how frequently family members and volunteers are involved as well as the tasks they pursue is lacking. The aim of the study is to describe and evaluate the involvement of family members and volunteers in SHA. Special Care Units (SCU) are observed in comparison. In january 2009, all identified SHA and SCU in the city of Berlin were included in a cross-sectional survey as part of the DeWeGE-study. The DeWeGE-study was the first one on SHA in the city of Berlin. Data was collected using a written, standardised questionnaire. We collected data related to the frequency and tasks of family members and volunteer involvement as well as to the residents characteristics. 963 residents of 105 SHA and 17 SCU were included. More persons suffer from dementia in SCU than in SHA. SHA offer events to inform relatives and volunteers about their possible involvement less often than SCU. Family members are involved in meaningful activities in around 50 percent of all SHA and SCU. The proportion of family members who are present in the unit at least once per week is significantly higher in SCU than in SHA. No statistically significant difference between SHA and SCU is found regarding the involvement of volunteers. In SHA, legal representatives are more often paid professionals than in SCU. The real involvement of family members and volunteers in SHA does not reflect the conceptual propositions of this care arrangement. PMID- 22097405 TI - [Determining the quality of technical aids in homely care contexts. A study of the survey instruments QUEST2.0 and KWAZO]. AB - The data on the supply of technical aids are insufficient in Germany, particularly with regard to quality aspects. Thus this article will demonstrate possibilities to improve the data quality. The analysis of the current supply situation for care aids and the detection of the relevance of the subject with care and aid statistics lead to the following research questions: Which instruments are able to measure the care-quality of technical aids for insured people older than 65 years in home care? And: Furthermore is their prediction sufficient to cause a more efficient care in this sector? The systematical research found two instruments, which met two criteria: 1.) Measurement of satisfaction from a user perspective. 2.) General applicability for many categories of aid. The studies were tested for evidence of reliability, validity and applicability. The Quebec User Evaluation of Satisfaction with Assisitive Technologies (QUEST2.0, 12 items) and the KWAZO instrument (7 items), developed in the Netherlands were used. Both instruments are tested for validity and reliability and in terms of their practical applicability in the nursing process events. It is necessary to consider are whether and in what way the two instruments made in a standardized comprehensive care and support needs assessment available in Germany. PMID- 22097406 TI - [Ambulatory nursing for patients with chronic obstructive lung disease. Do specialized nursing personnel help in ambulatory care nursing programs?]. PMID- 22097407 TI - [When the doctor allows the blood pressure to rise....]. PMID- 22097408 TI - [When facilities update nursing documentation... Electronic data processing instead of paper!]. PMID- 22097409 TI - [Communication in routine nursing care. Surprising reactions]. PMID- 22097410 TI - [After the war: US Americans influence the professionalization of nursing. A new nursing elite is created. The "Hollywood Nurses"]. PMID- 22097411 TI - [Dementia: technical monitoring systems in nursing. Where are you walking...?!]. PMID- 22097412 TI - [UrgoClean: a new wound dressing features high absorption and uptake of fibrous deposits]. PMID- 22097413 TI - [Nurses will assume a key role in pain therapy]. PMID- 22097414 TI - [Opioids play a major role in multimodal pain therapy"]. PMID- 22097415 TI - [Portrait of Louise Hagan]. PMID- 22097416 TI - [The world fight against infections. The first international conference in Geneva on the prevention and control of infections, a success!]. PMID- 22097417 TI - [Subcutaneous immunotherapy for the treatment of allergies]. PMID- 22097418 TI - [Myths and realities. Nursing care documentation]. PMID- 22097419 TI - [Allergy or food intolerance: how to distinguish between the two]. PMID- 22097420 TI - [Shaking. Evaluating and intervening]. PMID- 22097421 TI - [Goodbye to the flu? It is better to prevent it than to suffer from it!]. PMID- 22097422 TI - [Unwanted pregnancy. Emergency contraception at school. Before acting, we need to know how to listen]. PMID- 22097423 TI - [HIBOU: evaluating sleep disorders in children]. PMID- 22097424 TI - [Systemic scleroderma. A poorly understood illness]. PMID- 22097425 TI - [Living with a stoma]. PMID- 22097426 TI - [The SIPPE program. When intervention makes the difference]. PMID- 22097427 TI - [Blood pressure measurement at home. Why? For whom? How?]. PMID- 22097428 TI - [Vitamin D poisoning in infants. Preventing an overdose due to multiple forms and formats of liquid Vitamin D]. PMID- 22097429 TI - [Erectile dysfunction. Another option]. PMID- 22097430 TI - [Benlysta. Finally, the first medication for lupus]. PMID- 22097431 TI - [Abera and Yohanes. The scarifications of the Surmas]. PMID- 22097432 TI - [REER - CELI, CELI - REER?]. PMID- 22097433 TI - [Medium-term strategy for the specific management of pneumology hospitals and wards after the decentralization of the sanitary system]. AB - Identifying and promoting new management techniques for the descentralized pneumology hospitals or wards was one of the most ambitious objectives of the project "Quality in the pneumology medical services through continuous medical education and organizational flexibility", financed by the Human Resourses Development Sectorial Operational Programme 2007-2013 (ID 58451). The "Medium term Strategy on the specific management of the pneumology hospitals or wards after the descentralization of the sanitary system" presented in the article was written by the project's experts and discussed with pneumology managers and local authorities representatives. This Strategy application depends on the colaboration of the pneumology hospitals with professional associations, and local and central authorities. PMID- 22097434 TI - [Evolution of endemic tuberculosis in Olt county, Romania, between 1990 and 2008]. AB - A world-wide recrudescence of tuberculosis has been seen, due to the deterioration of the health state of the population from many areas of the world, because of increasing number of homeless persons, and also the immigrants from countries with TB epidemic. The present epidemiological context draw attention to the necessity of early detection of the disease and the beginning of early directly observed treatment, preferably ambulatory, if the sick person doesn't have other complications, isn't infected with multidrog resistant bacili and lives in a properly social environment for his support. For the evaluation of tuberculosis epidemic in Olt county, the authors realised a retrospective study on a period of over 15 years (1990-2008), based on the analysis of the main epidemiological indices of TB epidemic in this county compared with Romania: global incidence both in adults and children, for new cases nd relapses apart, incidence of MDR-TB (multidrug resistant-tuberculosis) cases, mortality through tuberculosis. Global incidence of TB in Olt county almost doubled between 1990 2008, reaching 147, 4 per hundred thousand, with much higher values compared with the national ones. Olt county presents constant values over the national ones between 1995-2008, due to the global incidence and also to the new cases and relapses. The incidence of new cases in children in 2008 (20,4 per hundred thousand) was below the national level (28 per hundred thousand). The risk of illness for the 0-14 years old children from Olt county was significantly lower in 2008 compared with the previous year, which, toghether with a number of MDR-TB cases under 15, signifies a regress of the epidemic. PMID- 22097435 TI - Is there delay in diagnosis of pulmonary tuberculosis in an intermediate-to-low TB incidence setting. AB - A cross-sectional study on pulmonary TB diagnosis delay in an intermediate TB incidence setting showed average patient's delay of 44 +/- 61.65 days and total delay of 103 +/- 148 days. Alcoholism, lack of TB cases in family, diabetes mellitus, relapse, cough or tachycardia (p< 0.01), absence of hemoptysis, dyspnea and anemia (p < 0.01), age > or = 40 (p < 0.05), negative auscultation and positive sputum smear findings (p < 0.05) were significantly associated with patient's delay > 30 days. Age < 40 years, negative auscultation and sputum smear findings (p < 0.01), female sex, city as residence (p < 0.05), absence of cough, sputum, weight loss, fever, excavation (p < 0.01), and night sweats (p < 0.05) were significantly associated with total delay > 103 days. Further population education and continual medical education are waranted. PMID- 22097436 TI - Mini-mediastinotomy under local anesthesia for biopsy of anterior mediastinal masses with airway compression. AB - INTRODUCTION: Management strategies for anterior mediastinal masses (AMMs) depend strongly on the histopathological diagnosis. The manifestations of these masses sometimes are an emergency because of large airway or great vessel compression which make general anesthesia challenging and hazardous and many authors have emphasized the dangers of general anesthesia in such patients. METHODS: This prospective study carried on 23 patients with AMMs and large airway or vessel compression via mini-mediastinotomy under local anesthesia for taking histological biopsy. RESULTS: . A definite histolopathological diagnosis was made in all cases. Morbidity was seen in one patient with entering the pleural cavity, there was no mortality. Out of 23 patients, 9 patients had already undergone less invasive procedures without definite diagnosis. CONCLUSIONS: Mini-mediastinotomy under local anesthesia for diagnostic biopsy in AMMs with airway compression is safe, minimally invasive, effective, and is useful in therapeutic decision making for AMMs. PMID- 22097437 TI - [Clinical features and course of patients with tuberculosis requiring intensive care]. AB - BACKGROUND: To describe the characteristics of patients with tuberculosis (TB) requiring intensive care and to identify the risk factors for mortality. METHODS: We conducted a retrospective, cohort study, between January 2006 and December 2009. The patients with TB, admitted in Pneumology Clinic Hospital, Iasi, requiring advanced life support in intensive care unit (ICU), were included. We assessed different clinical parameters to identify the factors that predict in hospital mortality. The primary outcome was the in-hospital mortality. RESULTS: During the study period, 27 patients with TB required intensive care. Of them, 16 (59.3%) had acute respiratory failure and 6 (22.2%) required mechanical ventilation. Eighteen (66.7%) patients died. Acute respiratory failure, acute hepatic failure and mechanical ventilation significantly correlate with a high in hospital mortality rate. CONCLUSIONS: In this study we found a high mortality rate in TB patients requiring intensive care, identifying some risk factors. PMID- 22097438 TI - A new model for cystic fibrosis management: control concept. AB - Traditional medical care considers symptomatic and objective findings of disease as the main outcome measure. However, modern medical practice defines health as a complete state of well being including physical state and patient's perception of social and psychological well being. Therefore, the main aim of therapeutic management needs to be "the control of disease related and unrelated to the health condition of the individual in terms of functional and emotional well being". This necessitates evaluation of control status in cases with cystic fibrosis via evaluation of symptomatic and physical findings with laboratory techniques and psycho-somatic instruments. The aim of this review article is to define the three main indicators of control and to provide initial ideas for development of a new instrument that covers all. PMID- 22097439 TI - [Endobronchial changes in sarcoidosis]. AB - The first case of endobronchial sarcoidosis was described by Benedict and Castelman in 1941. The endoscopic aspects in sarcoidosis can reveal: erythema, edema, network of capillary ectases, granularity, irregular mucosa thickening, macro and micro nodules in mucosa, bronchial and tracheal stenosis, distortions, tractions (including at the large and medium airways), sometimes bronchial ectases secondary to these modifications. The doctors must be aware of the possibility of affecting the great airways in sarcoidosis, such situation, although rare, could make for a difficult diagnosis, especially in the case of the tusigen syndrome or persistent and unexplained wheezing. The more the parenchimal disease progresses, the greater is the frequency of the airways being affected. PMID- 22097440 TI - [Functional evaluation before lung resection for cancer--international recommendations]. AB - Complications and disability after radical therapy for lung cancer can be predicted by preoperative functional evaluation. Functional tests and threshold values of the parameters have been described and included in a well-validated algorithm, ensuring functional reserve evaluation of candidates for pulmonary resection. There are no defined tests or cut-off values to provide predictions of complications after chemo-radiotherapy or limited pulmonary resections. PMID- 22097441 TI - Mucoepidermoid carcinoma of trachea in a 22 years old woman: a case report. AB - Mucoepidermoid carcinoma is a relatively common salivary glands tumor. This tumor is characterized by mucus secretion, cell type can be intermediate or squamous. Mucoepidermoid carcinoma of the bronchi and especially trachea is very unusual. We are reporting the case of a 22 years old female who presented with main complaint of exertional dyspnea and stridor for about 2 month. Bronchoscopy examination showed a mass with smooth surface in trachea. After surgery a low grade mucoepidermoid carcinoma was confirmed by pathological examination. PMID- 22097442 TI - [The Irish lesson--when will it apply also to Romania?]. AB - We are speaking every time about models but historically we are not considering the way made for obtaining them. In this paper we are reviewing the road for realizing common antismoking front in Ireland and where we failed in comparison in this introduction of the anti-smoking law. PMID- 22097443 TI - [Epidemiological problems: reflections on communication]. PMID- 22097444 TI - [Adult severe community-acquired pneumonia: from diagnosis to intensive care]. AB - Severe community-acquired pneumonia is defined as a pneumonia acquired in an extra-hospital setting requiring intensive care. Clinical scores such as the ATS modified rule can help the clinician to recognize quickly the patients needing ICU. Evidence based interventions decreasing mortality consist of rapid administration of antibiotics, by probably privileging an association containing a macrolide, as well as fast and specialized care of shock and respiratory failure. Severe community-acquired pneumonia is burdened by a short and long-term important mortality. PMID- 22097445 TI - [Drugs "look-alike, sound-alike": an important issue in infectious diseases]. AB - Incidents linked to the prescription of medications also referred to as "look alike, sound-alike" are frequent both in the ambulatory and in hospital sectors. These incidents are associated with relevant morbidity and mortality. Next to other specialties of medicine, infectiology is particularly affected. Strategies to reduce these risks have been devised, but available recommendations are frequently poorly observed. A heightened awareness regarding the "look-alike, sound-alike" problem among doctors as well as other health care professionals, regulatory agencies and the pharmaceutical industry would help assure and maintain increased patient safety and quality of care. PMID- 22097446 TI - [Traps in infectious serology]. AB - The role of serology in infectious disease diagnosis is highlighted by HIV and viral hepatitis diagnosis developed since the 80's. However, long before these recent developments serum reactivity played its role in diagnosing, active or previous severe bacterial infection in diseases such as typhoid fever (Widal), brucellosis (Wright test), syphilis (VDRL, Wassermann test), typhus (Weil-Felix test) etc. From early infection to immunity, serology analyzes the patient's immunological memory enabling the fight against infections. The resulting information depends on the type of pathogen, the site of infection, the host and the stage of disease. Together with the direct tests for the detection of pathogens, serological tests form the basis of microbiological diagnosis. To better understand the utility of serology, we will provide an overview and show its pitfalls. PMID- 22097447 TI - [HIV: vision of a cure]. AB - In 2008, Mr Brown, an HIV positive patient was healed of acute myeloid leukemia, after receiving an hematopoietic stem cell transplantation from a donor homozygous for the CCR5 gene variant delta32. He was able to recover a normal CD4 T cell count and his HIV viral load has remained undetectable, despite discontinuing antiviral therapy. This extraordinary case is a proof of concept that HIV can be cured and has boosted the research, especially in the field of gene therapy. Several groups are working on blocking the expression of the CCR5 and CXCR4 co-receptors, by using either RNA interference or zinc-finger nuclease tools. The aim of this article is to describe their actual stage of development. PMID- 22097448 TI - [Infections related to water activities]. AB - Infections acquired by exposure to water are common. The evolution of these infections found in our region is benign. However, some acquired in our regions or during travel abroad, may have a severe clinical course that requires early diagnosis. This article proposes a non-exhaustive review of the most common infections encountered in our regions or acquired abroad. The review excludes gastrointestinal infections acquired after ingestion of contaminated water. PMID- 22097449 TI - [Nontuberculous mycobacterial lung infections]. AB - Diagnosis of nontuberculous mycobacterial infection, which most often cause pulmonary disease, are increasing. Only a few of the numerous mycobacteria species are clearly pathogenic. Patients, either immunocompetent or immunocompromised, with orwithout underlying disease, are contaminated from the environment. Diagnosis, according to standardized criteria, is based on clinical picture, radiological exams and positive microbiological samples, usually on more than one occasion (slow growing culture and PCR). There are several typical presentations, such as tuberculosis-like disease and lung nodules associated with bronchiectasis. Treatment combines several antimicrobials, is long (occasionally more than one year) and is not always successful. PMID- 22097451 TI - [It is necessary to fill in the gap which separates scientific research from clinical practice]. PMID- 22097450 TI - [Pit falls in the emergency walk-in clinic: lower limb (2)]. AB - The lower limb is the seat of many traumatic lesions especially the foot and ankle. To misdiagnose these injuries leads to pain, instability, early arthritis and poor results. Clinical examination is very important and also standard X rays. New imaging techniques such as MRI will help to delineate some difficult to see lesions such as Lisfranc's fracture-dislocations, osteochondral lesions or occult hip fractures. PMID- 22097452 TI - [Inadvertent exclusion]. PMID- 22097453 TI - [A genetically engineered human pancreatic beta cell line]. PMID- 22097454 TI - [The end of the book and the computer]. PMID- 22097455 TI - [Giving birth anonymously versus the "towers of abandonment" (1)]. PMID- 22097456 TI - [Physicians: urgency at home]. PMID- 22097457 TI - Bioconjugated quantum dots as fluorescent probes for biomedical imaging. AB - Luminescent semiconductor quantum dots have become an important class of fluorescent labels for biological and biomedical imaging. In comparison with conventional organic dyes and fluorescent proteins, quantum dots have extraordinary fluorescent properties including high brightness, high resistance to photobleaching and tunable wavelengths. In this review, we briefly discuss the properties and modification of quantum dots. We focus on the applications of quantum dots in biomedical imaging, including molecular detection, live cell imaging and in vivo imaging. The toxicity of the quantum dots to cells and animals is also discussed. PMID- 22097458 TI - Information processing schemes based on monolayer protected metallic nanoclusters. AB - Nanostructures are potentially useful as building blocks to complement future electronics because of their high versatility and packing densities. The fabrication and characterization of particular nanostructures and the use of new theoretical tools to describe their properties are receiving much attention. However, the integration of these individual systems into general schemes that could perform simple tasks is also necessary because modern electronics operation relies on the concerted action of many basic units. We review here new conceptual schemes that can allow information processing with ligand or monolayer protected metallic nanoclusters (MPCs) on the basis of the experimentally demonstrated and theoretically described electrical characteristics of these nanostructures. In particular, we make use of the tunnelling current through a metallic nanocluster attached to the electrodes by ligands. The nanostructure is described as a single electron transistor (SET) that can be gated by an external potential. This fact permits exploiting information processing schemes in approximately defined arrays of MPCs. These schemes include: (i) binary, multivalued, and reversible logic gates; (ii) an associative memory and a synchronization circuit; and (iii) two signal processing nanodevices based on parallel arrays of MPCs and nanoswitches. In each case, the practical operation of the nanodevice is based on the SET properties of MPCs reported experimentally. We examine also some of the practical problems that should be addressed in future experimental realizations: the stochastic nature of the electron tunnelling, the relatively low operation temperatures, and the limited reliability caused by the weak signals involved and the nanostructure variability. The perspectives to solve these problems are based on the potentially high degree of scalability of the nanostructures. PMID- 22097459 TI - Superior neuroprotective effects of cerebrolysin in heat stroke following chronic intoxication of Cu or Ag engineered nanoparticles. A comparative study with other neuroprotective agents using biochemical and morphological approaches in the rat. AB - The possibility that cerebrolysin, a mixture of several active fragments of neurotrophic factors and peptides induces neuroprotection following nanoparticles induced exacerbation of brain damage in heat stroke was examined in a rat model. For this purpose, the therapeutic efficacy of Cerebrolysin (2.5 or 5 ml/kg) recommended for stroke treatment was used in comparison with other drugs in standard doses recommended for such therapy in clinical situations e.g., levetiracetam (44 mg/kg), pregabalin (200 mg/kg), topiramate (40 mg/kg,i.p.) and valproate (400 mg/kg). Rats subjected to 4 h heat stress in a biological oxygen demand (BOD) incubator at 38 degrees C (Rel Humid 45-47%; Wind vel 22.4 to 25.6 cm/sec) developed profound behavioral symptoms of heat stroke e.g., hyperthermia, profuse salivation, prostration and gastric ulcerations in the stomach. These rats also exhibited marked brain pathology at this time. Thus, breakdown of the blood-brain barrier (BBB) to proteins associated with brain edema formation could be seen in these heat stressed rats as compared to control groups. The edematous brain areas showed profound neuronal damage and/or distortion in large areas of the neuropil. These pathological symptoms were further exacerbated in Cu or Ag nanoparticles treated group (50-60 nm particle size, 50 mg/kg, i.p./day for 7 days) after identical heat stress on the 8th day. Pretreatment with cerebrolysin (2.5 ml/kg, i.v.) daily for 3 days in normal rats before heat stress significantly reduced the behavioral stress symptoms and the breakdown of the BBB function, edema formation and neuronal injuries. However, the magnitude and intensity of these neuroprotective effects were much less intense in all other drug treated rats after similar heat stress. On the other hand, almost double dose of cerebrolysin (5 ml/kg) was needed to achieve comparable neuroprotection in nanoparticles treated animals after heat stress. Whereas, double dose of all other compounds was much less effective in inducing neuroprotection in nanoparticles treated heat-exposed animals. These observations are the first to show that cerebrolysin exerts the most superior neuroprotective effects in heat stress as compared to other neuroprotective agents on brain pathology in normal and in nanoparticles treated group. Furthermore, cerebrolysin in double dose was the most effective in inducing neuroprotection in nanoparticles treated heat exposed rats on brain pathology as compared to double doses of other drugs. Taken together, our results show that cerebrolysin has the most superior neuroprotective effects on brain pathology in heat stroke in both normal and nanoparticles treated rats as compared to other contemporary neuroprotective agents, not reported earlier. PMID- 22097460 TI - Detection of malathion, fenthion and methidathion by using heparin-reduced gold nanoparticles. AB - Green-synthesized gold nanoparticles were utilized for the detection of organophosphorous pesticides. Heparin, one of glycosaminoglycans, was used as a reducing and stabilizing agent. The reaction conditions were optimized, and high resolution-transmission electron microscopic images revealed gold nanoparticles of various shapes. Organophosphorous pesticides in water were detected by simply mixing them with gold nanoparticles. NaCl induced a color change in the mixed solution from wine-red to purple-blue that was dependent on the pesticide concentration in the range of 10-1,000 ppb. Gold nanoparticles were immobilized on a silica gel matrix in order to prepare solid supports for removing pesticides. The incorporation of atomic gold and heparin bound to 2 g of silica gel was determined 4,058 ppm and 33 microg as measured by inductively coupled plasma-atomic emission spectrophotometry and carbazole assay, respectively. AuNPs immobilized silica gel columns were successfully applied for removing fenthion in water confirmed by RP-HPLC and FT-IR analyses. PMID- 22097461 TI - pH dependent spontaneous growth of ellagic acid assemblies for targeting HeLa cells. AB - Herein, we have studied the self-assembly and the spontaneous growth of microassemblies of the plant polyphenol ellagic acid for HeLa cancer cell imaging and therapy. The growth of the assemblies was studied at varying pH over time. It was found that initially microspheres were formed which gradually transformed into microfibers via nucleation and polymerization process. The optimum growth of microfibers was found to be in the pH range of 6-8. We have shown that the microfibers successfully adhered to the HeLa cell membranes and inhibited their proliferation. This biological approach, using assemblies derived from plant polyphenols, may be used for direct cellular drug delivery and may potentially help develop a simple and economical method to create building blocks with desired properties for a new generation of sensors, bioimaging and drug delivery systems. PMID- 22097462 TI - Sorting the unique chirality, right handed single wall carbon nanotubes via the dye modified ssDNA. AB - The unique (n, m) SWCNTs have both left- and right-handed helicity and they are enantiomers, and unique chiral SWCNTs with single helicity haven't achieved yet. In our studies the aromatic fluorescence molecule, (R+) 5'-Hexachloro-Fluorescein Phosphoramidite (HEX), was linked to DNA, and this new polymer could help us to get unique chiral SWCNT (11,1) with only right-handed species, and this result is confirmed by AFM, HRTEM, NIR, SRCD, and Raman studies. PMID- 22097463 TI - Synthesis of retinyl palmitate catalyzed by Candida sp.99-125 lipase immobilized on fiber-like SBA-15 mesoporous material. AB - Candida sp.99-125 lipase was suitable for transesterification of fats and oils to produce fatty acid methyl ester. The adsorption of Candida sp.99-125 lipase onto the fiber-like SBA-15 mesoporous material has been studied. The unaltered structural order of the fiber-like SBA-15 before and after the adsorption has been confirmed by FT-IR, SEM and N2 adsorption. The amount of adsorbed Candida sp.99-125 lipase depends both on the solution pH and reaction time. Good adsorption capacity of Candida sp.99-125 lipase on fiber-like SBA-15 may be due to solution pH from 5.0 to 9.0 especially at 7.0 (93.99 mg enzyme per gram silica is obtained and the activity recovery is 281.05%). A high lipase loading (135.9 mg enzyme per gram silica) was obtained, but it did not produce a proportionate level of catalytic activity. The immobilized Candida sp.99-125 lipase showed increased adaptability in the hydrolysis of p-nitrophenyl acetate compared to free Candida sp.99-125 lipase at pH 5.0-9.0. Meanwhile, the immobilized Candida sp.99-125 lipase showed higher thermal stability than that of free Candida sp.99 125 lipase. And the synthesis of retinyl palmitate in organic solvent with the immobilized Candida sp.99-125 lipase was investigated. The influence factors, such as: the solvent used, the molar ratio and concentrations of substrates, the reaction time and the amount of lipase were studied and optimized. In the conditions of transesterificating 0.164 g retinyl acetate and 0.32 g palmitic acid, 10 mL of solvent hexane, 1:4 of mass ratio of lipase to retinyl acetate, and 6 hours of reaction time, 74.6% of retinyl acetate was converted into retinyl plamitate. PMID- 22097464 TI - Curcumin associated magnetite nanoparticles inhibit in vitro melanoma cell growth. AB - Curcumin is a natural product possessing therapeutic properties but the low water solubility of this compound limits its use. We have successfully incorporated curcumin into a bilayer of dodecanoic acid attached to magnetite nanoparticles in an effort to maximize solubility and delivery efficiency. Curcumin/magnetite nanoparticles were characterized using diffused reflectance infra-red fourier transform spectroscopy (DRIFTS) and X-ray powder diffraction (XRD). Moreover curcumin associated magnetite nanoparticles inhibited in vitro melanoma cell growth. An inhibitory concentration (IC50) of 66.0 +/- 3.0 microM (48 +/- 2.2 microg-iron/mL) was observed for the curcumin/magnetite nanoparticles. Fluorescent microscopy revealed that curcumin associated magnetite nanoparticles were internalized by the melanoma cells and remained in the cytoplasm. The curcumin/magnetic nanoparticles synthesized in this study possess magnetic and water solubility properties making this a novel curcumin formulation with therapeutic potential. PMID- 22097465 TI - Targeted labeling of cancer cells using biotin tagged avidin functionalized biocompatible fluorescent nanocrystals. AB - The present study details the development of biotin tagged avidin functionalized Zinc Sulphide [ZnS] nanocrystals through a simple aqueous chemistry route at room temperature for targeted imaging applications. Surface functionalization of Manganese doped ZnS nanocrystals with L-cysteine provided functional groups that facilitated its conjugation to avidin. Further biotinylation of these particles through the strong non-covalent interaction between biotin and avidin enabled highly specific labeling of the biotin receptors on human hepatocellular carcinoma (HepG2) cells. The nanobioconjugates thus developed exhibited stable and brilliant fluorescence upon labeling the biotin receptors on cells as observed through fluorescence microscopy. Characterization studies using X-ray diffraction, dynamic light scattering as well as Fourier transform infrared spectroscopy revealed the bioconjugated particles to be appropriately functionalized and stable, with size ranging from 50 to 80 nm. Cytotoxicity of this material system evaluated using MTT, LDH leakage and apoptosis assay revealed its non-toxic nature even for high concentrations extending upto 250 microM and 48 hours of incubation. Our results confirmed that biotinylated ZnS nanocrystals offer great potential for highly specific labeling and targeted imaging of cancer cells. PMID- 22097466 TI - Photocatalytic bactericidal mechanism of nanoscale TiO2 films on Escherichia coli. AB - Two kinds of nanoscale TiO2 films were prepared by magnetron sputtering and screen printing methods, respectively. Results show that both phase composition and specific surface area of the film affect the photocatalytic bactericidal efficiency. Time-series in situ atomic force microscopy (AFM) observation were further used to characterize the cellular responses of Escherichia coli (E. coli) in photocatalytic process. Some nanosized patches were found on the bacterial surface in the forepart of photocatalytic reaction. It suggested that the photocatalytic attack induced the self-protection of bacteria at first. Subsequently, some cracks on the surface and the enlargement of cell body indicated that the cell wall was damaged and lost its structure supporting function, and it eventually led to the death of bacteria. PMID- 22097467 TI - Single nucleotide variation detection on 3D DNA microarray by ligation of two terminal-modified universal probes. AB - Exploiting the advantages of three-dimensional (3D) DNA microarray, we put forward a novel strategy termed "ligation of two-terminal-modified universal probes" for single nucleotide variation (SNV) detection on 3D microarray. By performing specific ligation reaction between the unmodified hybridization primer with 3' hydroxyl terminus and the universal probe with phosphorylated 5' terminus and fluorescently labeled 3' terminus, two point mutations (C3206T and A5301G) in the PCR products immobilized on the 3D polyacrylamide gel DNA microarray were accurately discriminated. This method can not only maintain the predominance of 3D DNA microarray as a platform with high through-put, but also can exert this predominance to the cases of detecting a small quantity of samples and multiple SNVs since four universal probes can be employed to detect all SNVs, therefore, it is more feasible for laboratory research and provide an effective tool for clinical diagnosis. PMID- 22097468 TI - Visualisation of morphological interaction of diamond and silver nanoparticles with Salmonella Enteritidis and Listeria monocytogenes. AB - Currently, medicine intensively searches for methods to transport drugs to a target (sick) point within the body. The objective of the present investigation was to evaluate morphological characteristics of the assembles of silver or diamond nanoparticles with Salmonella Enteritidis (G-) or Listeria monocytogenes (G+), to reveal possibilities of constructing nanoparticle-bacteria vehicles. Diamond nanoparticles (nano-D) were produced by the detonation method. Hydrocolloids of silver nanoparticles (nano-Ag) were produced by electric non explosive patented method. Hydrocolloids of nanoparticles (200 microl) were added to bacteria suspension (200 microl) in the following order: nano-D + Salmonella E.; nano-D + Listeria monocytogenes; nano-Ag + Salmonella E; nano-Ag + Listeria monocytogenes. Samples were inspected by transmission electron microscopy. Visualisation of nanoparticles and bacteria interaction showed harmful effects of both nanoparticles on bacteria morphology. The most spectacular effect of nano-D were strong links between nano-D packages and the flagella of Salmonella E. Nano Ag were closely attached to Listeria monocytogenes but not to Salmonella E. There was no evidence of entering nano-Ag inside Listeria monocytogenes but smaller particles were placed inside Salmonella E. The ability of nano-D to attach to the flagella and the ability of nano-Ag to penetrate inside bacteria cells can be utilized to design nano-bacteria vehicles, being carriers for active substances attached to nanoparticles. PMID- 22097469 TI - Nano rods for coloured glasses obtained by hybrid sol-gel coating. AB - Many new materials are now allowing new properties thanks to nanotechnology because this domain of physics gives possibilities to optimize targeted properties even if these materials react in very various influential parameters. Architectural, automotive, bone pathologies, environment, display applications are some concerned domains. The sol-gel process is a method allowing the realisation of coats at ambiant temperature, thus it is possible to realize Liquid Crystal Display (LCD), water-repellent coatings on privacy glass, antireflective coatings, hydrophobic or hydrophilic surfaces, bone tissue regeneration. In this study, the purpose is to show the thermal influence on a covered glass with a complex hybrid sol-gel solution. This coated glass is going to change color from red to orange under the heat influence. This color change effect comes from the evolution of various compounds organizations then/or from their loss during the degassing sequence. We show in spite of the complexity of the process that the responsible is mainly the organic dye. Thus the structure of the heated glass at 250 degrees C looks radically different than the heated one at 350 degrees C. SEM measurement allows to identify the surface compositions and to determine the elementary composition along the sample's cross section. TGA is used to justify a mass loss when samples are annealed. UV/Visible measurement is realized by two methods: in-line transmission to evaluate luminous flux and thus give colorimetric dot in the normalized CIE diagram and diffuse transmission to observe the size influence of the pigments. Infrared Reflectivity allows to evaluate the influence of species on the structure and to better target the nature of the lost compounds during annealing. TEM measurement proves that the obtained iron particles are nano rods for both samples. PMID- 22097470 TI - Interface and temperature dependent magnetic properties in permalloy thin films and tunnel junction structures. AB - Magnetization dynamics and field dependent magnetization of different devices based on 25-30 nm thick Permalloy (Py) films: such as single Py layers (Py/MgO; Py/CoFeB/Al2O3) and Py inserted as a magnetic layer in magnetic tunnel junctions (Py/CoFe/Al2O3/CoFe; Py/CoFeB/Al2O3/CoFe; Py/MgO/Fe) have been extensively studied within a temperature range between 300 K down to 5 K. The dynamic response was investigated in the linear regime measuring the ferromagnetic resonance response of the Py layers using broadband vector network analyzer technique. Both the static and the dynamic properties suggest the possible presence of a thermally induced spin reorientation transition in the Py interface at temperatures around 60 K in all the samples investigated. It seems, however, that the details of the interface between Py and the hardening ferromagnet/insulator structure, the atomic structure of Py layers (amorphous vs. textured) as well as the presence of dipolar coupling through the insulating barrier in the magnetic tunnel junction structures could strongly influence this low temperature reorientation transition. Our conclusions are indirectly supported by structural characterization of the samples by means of X-Ray diffraction and high resolution transmission electron microscopy techniques. Micromagnetic simulations indicate the possibility of strongly enhanced surface anisotropy in thin Py films over CoFe or CoFeB underlayers. Comparison of the simulations with experimental results also shows that the thermally-induced spin reorientation transition could be influenced by the presence of strong disorder at the surface. PMID- 22097471 TI - Reverse micelle microstructural transformations induced by surfactant molecular structure, concentration, and temperature. AB - We have investigated the microstructural transformations of nonionic surfactant reverse micelles induced by surfactant molecular architecture, surfactant concentration, and temperature in nonaqueous media. The investigations were based on small-angle X-ray scattering (SAXS) and rheometry techniques. Polyglycerol polyoleic acid esters spontaneously self-assembled into reverse micelle in n decane under ambient conditions, whose shape, size, and internal structure could be controlled by the surfactant molecular architecture, concentration, and temperature. The maximum size of the micelles was found to increase with an increase in the hydrophilic headgroup size of the surfactant. On the other hand, an opposite trend was observed with an increase in the number of oleate chain per surfactant molecules, which was well supported by rheology data; viscosity decreased with the number of oleate chain per surfactant molecule. The SAXS and rheology data have shown a clear evidence of one dimensional micellar growth with increase in the surfactant concentration. The relative viscosity, eta(r), of the reverse micelle exhibited steeper concentration dependence behavior than those predicted for a dispersion of spherical particles based on the Krieger-Dougherty relation which provided a clear evidence of the presence of elongated micelles at higher concentration. An ellipsoidal prolate-to-sphere type transition was observed upon heating. PMID- 22097472 TI - Chiral recognition of mandelic acid by L-MA derivative-modified sensor in liquid environment. AB - This study demonstrates a new approach for the highly selective molecular recognition of chiral mandelic acid using an L-mandelic acid derivative with an optically active hydroxyl group as the selector. The proposed method is based on quartz crystal microbalance (QCM) detection combined with functional multilayer film techniques in a liquid environment. The present chiral recognition results suggest that the L-mandelic acid derivative is an excellent resolving agent for detecting chiral mandelic acid. PMID- 22097473 TI - Chiral zinc phenylalanine nanofibers with fluorescence. AB - Chiral Zn(II)/D-,L-phenylalanine (Phe) bio-coordination polymer nanofibers with fluorescence were prepared by fast coordination-assisted assembly. The synthetic strategy is based on the fact that the Zn2+ ions were linked to oxygen atoms from carboxylate groups of the D- or L-amino acid by coordination interactions to form the chiral polymers. The Zn(II)/D-,L-Phe nanofibers had homogeneous diameters in the range of 700-900 nm and ultra-long length in several hundred micrometers, and the surface of the fiber was extremely smooth. In addition, the enantiomers of Zn(II)/Phe nanofibers exhibited both optical activity and fluorescent property in the solid state, which has great potential for application in the field of biomimetic nanofabrication and micro-/nano-optoelectronics. PMID- 22097474 TI - Average plasmonic enhancement of molecules-doped Au-NS@SiO2 on fluorescence. AB - The average plasmonic enhancement of Au nanoshell (Au-NS) coated by a molecules doped silica layer (Au-NS@SiO2) on molecular fluorescence is studied theoretically to estimate the overall performance of a large number of Au NS@SiO2. Using Mie theory and dyadic Green's functions, analytical solutions of the excitation rate and the apparent quantum yield are obtained to calculate the enhancement factor of Au-NS@SiO2 on the fluorescence of a molecule with a specific orientation and location at a specific excitation wavelength lambda ex and an emission wavelength lambda em. Subsequently, the average enhancement factor (AEF) is calculated by averaging all possible orientations and locations of the molecule. For example, AEF of Au-NS@SiO2 (a3 = 50 nm t2 = 15 nm, t1 = 25 nm) is 4.544 for a NIR fluorescence at lambda ex = 780 nm and lambda em = 820 nm. Our results show that Au-NS is a broadband enhancer for NIR fluorescence; the bandwidth and the peak depend on the core size and the thickness of Au shell. PMID- 22097475 TI - The effect of tetrafluoromethane plasma post-treatment on the electrical property of tungsten oxide nanowires. AB - The effects of tetrafluoromethane (CF4) plasma on the surface morphology, chemical compositions, and electrical property of tungsten oxide (W18O49) nanowires are investigated. The nanostructured tungsten oxide nanowires with average length of 250-350 nm were self-catalytically grown on Si substrate. By post-treatment with CF4 plasma for 10 min, the W18O49 nanowires on the substrate showed the highest current response. Longer CF4 plasma post-treatment time demonstrated higher etching effect which demolished the nanowires and resulted in lower conductivity of the samples. The disintegration of the W18O49 nanowires layer after CF4 plasma treatment, revealed physically by the decrease of the average thickness and chemically by the decrease of XRD peak ratio (I 23.0/I 26.0), was closely related to the overall electrical performance. The etching effect was further reveled by Raman spectra showing the evolution of O-W-O and W=O characteristics with the increased post-treatment time. Moreover, the improvement of the electrical property of W18O49 nanowires was elucidated by the exposure rate to explain the mechanism of plasma post treatment in three stages: passivation, degradation and ablation. The maximum exposure rate, corresponding to the maximum conductivity, was achieved by 10 min of CF4 plasma treatment. The time-differentiated exposure analyses confirmed the evolution of resistance of W18O49 nanowires on Si with different post-treatment time which supported the results of surface characterizations. PMID- 22097476 TI - Controlled synthesis and up-conversion emission of rare-earth tri-doped NaYF4 nanocrystals under femtosecond-laser excitation. AB - Cubic nanocrystal and hexagonal micro-rods NaYF4, with predictable size, shape and phase, have been successfully synthesized through hydrothermal reaction. The growth mechanism and the effect of mass transfer on the morphology of hexagonal micro-prism are both discussed in detail. The increase of tri-doping lanthanide ion concentration decreased the size of crystal particle, which was explained by the Arrhenius rate equation together combined with the Gibbs-Thomson relationship. Furthermore, the dopants did not only affect the sizes of tri-doped NaYF4 micro-rods, but also impacted upon fluorescence intensity. The fluorescence of tri-doped NaYF4: Nd3+/Yb3+/Er3+ system, excited by an 800 nm femtolaser, was intensified with the increase of doped lanthanide ions concentration. Nevertheless owing to the fluorescence quenching, the other two systems (NaYF4: Nd3+/Ho3+/Er3+ and NaYF4: Nd3+/Tm3+/Er3+) did not show the same phenomenon. PMID- 22097477 TI - Size selective excitonic transition energies in strongly confined CdSe quantum dots. AB - We report on the synthesis of CdSe nanocrystal quantum dots (QDs) of different radii (R). Size dependent optical properties like increase in the confinement energy with decreasing radius for different excitonic transitions are studied. Different excitonic transitions are calculated from the second derivative of UV vis absorption spectra of as synthesized CdSe QDs. The transitions are assigned to specific states by calculating the transition energies using effective mass approximation. A close matching of the transition energies with the experiment suggesting that the second derivative of the absorption spectra could provide a direct knowledge of the electronic transition for the direct band gap semiconductor quantum dots. PMID- 22097478 TI - Graphene-based nanostructured hybrid materials for conductive and superhydrophobic functional coatings. AB - A bi-functional, conductive and superhydrophobic, graphene-based nanostructured hybrid material was fabricated. In order to construct the bi-functional hybrid material, carbon nanotubes (CNT) and polyhedral oligomeric silsesquioxane (POSS) were introduced. The water contact angle (WCA) of the graphene/POSS/CNT coating reached about 155 degrees and its conductivity was about 1-10 S/cm. Such graphene based nanostructured hybrid materials could have great potential as an antistatic and self-cleaning coating in various applications. PMID- 22097479 TI - High-efficiency photocatalytic degradation of methylene blue using electrospun ZnO nanofibers as catalyst. AB - In this work, ZnO nanofibers (ZNFs) were successfully prepared via a simple electrospinning technique using polyvinylpyrrolidone (PVP) and zinc acetate dihydrate (Zn(CH3COO)2 2H2O) as precursors. The obtained ZNFs have an average diameter of ca. 95 nm and are composed of crystalline wurtzite phase. Methylene blue (MB) dye was used to investigate the photocatalytic performance of pure ZNFs. The study confirms that ZNFs have favorable catalytic activity, and the best degradation efficiency of MB can exceed 90% under UV light irradiation for 3 hours. In addition, we propose a possible photodegradation mechanism. PMID- 22097480 TI - Crystallographic phase induced electro-optic properties of nanorod blend nematic liquid crystal. AB - Ultrasmall ZnS or PbS nanorods encapsulated in fluid-like soft organic surfactants show excellent miscibility in the nematic liquid crystal (LC ZLI 4792) host resulting in a novel soft matter type blend with enhanced electro optic properties. The ultranarrow ZnS rods are of wurtzite phase and possess a chemical bipolarity and a net dipole moment. The centrosymmetric ultranarrow PbS rods possess a finite size and shape dependent inherent dipole moment despite their cubic rock-salt structure. When an electric field is applied, the blend aligns along the direction of the field producing a local unidirectional orientation of the rods and LC directors, and defining a unique axis for the system. The local ordering significantly affects the global ordering of the blend allowing a more rapid response of the electro-optic properties. The degree and switching speed of the blends depend upon the magnitude of dipole moments present in the dopant nanorods. We show how a non-mesogenic element designed with preferential crystallographic phase can be introduced within a LC for improvement of the switching properties of the LC blend. These types of unique blends are a model for fundamental conceptual advances in general understanding of interaction behaviour leading consequently to a significant technological advancement for superior device fabrication. PMID- 22097481 TI - Is dye mixture more suitable rather than single dye to fabricate dye sensitized solar cell? AB - The steady state and time resolved spectroscopic studies reveal that two xanthene dyes Rhodamine 6G (R6G) and Rhodamine B (RB), used in the present investigations, form ground state hydrogen -bonded complexes with meso-tetrakis(4-carboxyphenyl) porphyrin (TCPP). However, it is apparent that upon photoexcitation the H-bonding complexes formed in the ground state decompose into the individual reacting components. This presumption was confirmed from the observation of the presence of only static quenching mode in the steady state fluorescence of the dyes in presence of porphyrin. The photoelectrochemical properties of the free dyes and the mixtures of each dye with porphyrin are investigated by measuring incident photon-to-current conversion efficiency (IPCE) using ZnO electrode and also with TiO2 electrode. It is seen that Rhodamine B-porphyrin mixture has attained maximum IPCE among the four samples studied at approximately 550 nm using ZnO electrode. Using TiO2 electrode, slight improvement in the value of IPCE was found for the same mixture. Therefore Rhodamine B-porphyrin mixture may act as a good sensitizer for converting solar energy to electrical energy. PMID- 22097482 TI - Gold nanoparticle induces masking of amines and some therapeutic implications. AB - Citrate capped gold nanoparticles (GNP) are effective in masking protein amines. The extent of such masking is quantified using Fourier Transform Infra Red (FTIR) spectroscopy. A strong correlation is shown to exist between a shift of amide-II peak intensity (1600-1500 cm(-1)) caused by GNP and the number of exposed amines in a given protein. The result is validated using eight different proteins. The expected out-come of such masking is inhibition of interaction between any external ligand and such amines. The prediction is validated using a simple non enzymatic glycation of clinically important protein like crystallin. PMID- 22097483 TI - Atomic and electronic properties of realizable size single-crystal GaN nanotubes by first principles. AB - We studied the diameter and wall thickness dependent atomic and electronic properties of practical size single-crystal GaN nanotubes using first principle calculations. Single-crystal GaN nanotubes are similar to the hexagonal GaN nanowires, grown in the [0001] direction with [10-10] facets, except there is an axial hexagonal void in them. We first demonstrated that the atomic and electronic properties of these tubes are mainly determined by the thickness of their wurtzite walls; and their diameters have negligible effects. Then, considering the individual walls of GaN nanotubes in two-dimensional slab calculations we examine the bond distances, formation energy, band gap, effective electron mass and the evolution of electronic density of the states as a function of thickness for unsaturated and hydrogen-saturated slabs of GaN. Calculations revealed that the unsaturated dangling bonds at the surfaces induce defect states in the band gap region of unsaturated tubes. Therefore, regardless of diameter and wall thickness, their band gaps are always smaller than that of the bulk GaN. However, the band gaps of the hydrogen-saturated tubes are found to be amplified with respect to bulk GaN. The amplification in the band gaps as a function of wall thickness in the range of 5.6-16.9 A and 16.9-28.1 A scales with a factor of 1/d(0.9281) and 1/d(1.769), respectively. Our results show that, regardless of diameter, hydrogen saturated single-crystal GaN tubes with the wall thickness as small as 28.1 A would be stable and they would have a noticeably larger band gap with respect to the band gap of bulk GaN. PMID- 22097484 TI - The effect of arginine on gold nanoparticles in colloidal solutions and in thin films. AB - Gold nanoparticles were prepared in aqueous colloidal solutions and their interaction with L-arginine solutions at different concentrations was investigated by UV-vis spectroscopy, transmission electron microscopy (TEM) and atomic force microscopy (AFM). The shift towards red of the absorption maximum of gold nanoparticles with increasing L-arginine concentration and in time, and the apparition of a new large band at higher wavelength evidence the formation of assemblies of gold nanoparticles, mediated by the amino acid. TEM images present the progress in the building process of supermolecular structures. Further, the AFM images show the self assemblies of gold nanoparticles capped with L-arginine well ordered in large domains on silanized glass. As a model for the process, we suggest that the positively charged guanidinium group of L-arginine is anchored on the negative citrate capped gold nanoparticles, while the other two functionalities of L-arginine are involved in the bonding between gold nanoparticles. The ability of arginine to specifically bind gold nanoparticles could lead to an increased ability of proteins, containing arginine, to specifically bind to nanogold. Then, they bind other target proteins or different ligands underlying numerous biological and medical applications that range from nanoscale biosensors, cell-cell communications to targeted delivery of drugs to cancer cells. PMID- 22097485 TI - Carbon decorative coatings by dip-, spin-, and spray-assisted layer-by-layer assembly deposition. AB - We performed a comparative surface analysis of all-carbon nano-objects (multiwall carbon nanotubes (MWNT) or graphene oxide (GO) sheets) based multilayer coatings prepared using three widely used nanofilm fabrication methods: dip-, spin-, and spray-assisted layer-by-layer (LbL) deposition. The resultant films showed a marked difference in their growth mechanisms and surface morphologies. Various carbon decorative coatings were synthesized with different surface roughness values, despite identical preparation conditions. In particular, smooth to highly rough all-carbon surfaces, as determined by atomic force microscopy (AFM) and scanning electron microscopy (SEM), were readily obtained by manipulating the LbL deposition methods. As was confirmed by the AFM and SEM analyses, this finding indicated the fundamental morphological evolution of one-dimensional nano-objects (MWNT) and two-dimensional nano-objects (GO) by control of the surface roughness through the deposition method. Therefore, an analysis of the three LbL-assembly methods presented herein may offer useful information about the industrial use of carbon decorative coatings and provide an insight into ways to control the structures of multilayer coatings by tuning the morphologies of carbon nano objects. PMID- 22097486 TI - Nanostructure and chemical characterisation of individual NiFe/Pt multilayer nanowires. AB - NiFe/Pt multilayer nanowires have been successfully fabricated by pulse electrodeposition into the channels of porous anodic aluminum oxide (AAO) templates, and characterized at the nanoscale. Individual nanowires have uniform structure and regular periodicity. The NiFe and Pt layers are polycrystalline, with random orientation fcc lattice structure crystallites and grain sizes 3-10 nm, and the average layer growth rate is 30 nm/s for NiFe and 4 nm/s for Pt. Nanoscale chemical analysis of individual NiFe/Pt nanowires by EDX and EELS shows that they contain alternating NiFe and Pt layers, with a small approximately 1% inclusion of Pt in the NiFe layer due to electrochemical co-deposition. PMID- 22097487 TI - Synthesis and morphological control of europium doped cadmium sulphide nanocrystals. AB - Europium doped cadmium sulphide (Cd(0.98)Eu(0.2)S) nanostructures were synthesised by chemical co-precipitation method using ethylene glycol (EG) and deionized water (Eu:CdS-1), and isopropyl alcohol (IPA) and deionized water (Eu:CdS-2) as mixed solvents. It has been found that the nanostructure of the europium doped CdS can be controlled by simply varying the mixed solvent system. Powder XRD pattern reveals the formation of hexagonal (wurtzite) and cubic (zinc blende) structure for Eu:CdS-1, and Eu:CdS-2, respectively. The crystallite size of the sample prepared using IPA and deionized water was measured to be 2.64 nm which is much smaller than that of the sample prepared using EG and deionized water as mixed solvent (3.65 nm). Morphology of the materials can also be changed from flower shaped crystals to paddy like structures by varying the mixed solvents. Band gap values of Eu3+ doped CdS nanocrystals synthesized from two different solvents were estimated using UV-reflectance spectra. The size and crystallinity of the samples were confirmed by HRTEM and SAED analysis. A significant change in the PL emission of the CdS nanocrystals was observed for the europium doped CdS which is mainly due to the presence of EU3+ ions which also play a significant role in the energy transfer process. It was also observed that the shift in the emission and efficiency depends on size and shape of the synthesised nanoparticles. PMID- 22097488 TI - Direct measurements of the Young's modulus of a single halloysite nanotube using a transmission electron microscope with a bending stage. AB - Halloysite nanotubes (HNTs) are a naturally occurring nanotubular aluminosilicate mineral, which has been used to prepare nanocomposites with exceptional mechanical properties. In order to understand the roles of nanotubes during the deformation and fracture of nanocomposites, a state-of-the-art transmission electron microscope (TEM) with a bending stage was used to measure the Young's modulus of individual HNTs. TEM micrographs showed that the HNTs were surprising flexible and could be bent to almost 90 degrees without fracture. There was no observable reduction in the cross-sectional area of the bent HNTs. The findings suggest that HNTs, as a nanofiller, have a good potential to be used in high performance structural materials, especially polymer-based nanocomposites. PMID- 22097489 TI - Microwave-assisted facile synthesis of palladium nanoparticles in HEPES solution and their size-dependent catalytic activities to Suzuki reaction. AB - Palladium nanoparticles (NPs) were successfully synthesized via a rapid and facile microwave route in HEPES (2-[4-(2-hydroxyethyl)-1 piperazinyl]ethanesulfonic acid) buffer solution. The shape- and size-controlled Pd nanoparticles could be obtained by one-step method without dependence of seed mediated growth. The capping agent plays a key role in the formation of Pd NPs with different shape and size, which could be tuned by varying capping agents such as polyvinylpyrrolidone (PVP), cetyltrimethylammonium bromide (CTAB), sodium citrate (Na3(cit)) and potassium bromide (KBr). The size-dependent catalytic activities of the obtained Pd NPs for Suzuki coupling reaction were also investigated. It demonstrated that the catalytic activity of Pd NPs was enhanced regularly with the decrease of particle size. Pd NPs less than 10 nm exhibited better catalytic activities for Suzuki reaction than the commercial Pd/C catalyst. Pd/MWCNTs and Pd/SBA-15 nanocomposites were also prepared by a facile method and afforded good catalytic activity and reusability. This "green" synthetic protocol could be used as a general method for the rapid synthesis of transition metal nanoparticles. PMID- 22097490 TI - The morphology-dependent photocatalysis for rhodamine B degradation over Bi2WO6 hierarchical nanostructure. AB - In this paper, the nanostructured Bi2WO6 with different hierarchical morphologies was synthesized via a warmly hydrothermal route. The structure and morphology of the as-prepared Bi2WO6 products were characterized by X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), UV-vis absorption spectroscopy (UV-Vis) and N2-sorption analysis. The photocatalytic efficiency of Bi2WO6 was investigated by photodegradation of rhodamine B (RhB) under visible light irradiation. The present work demonstrated that Bi2WO6 with four different hierarchical structures was effective visible-light-driven photocatalytic functional material for environmental purification. Moreover, the nest-like Bi2WO6 exhibited superior photocatalytic effects on rhodamine B degradation compared with other three Bi2WO6 morphologies. The excellent catalytic effect of the nest-like Bi2WO6 was attributed to its unique structural property and large surface area. The relationship between morphology and photocatalytic performance was discussed in detail. The photocatalytic mechanism for the degradation of RhB was also investigated, which revealed the important role of morphology in improving the photocatalyitc activities of Bi2WO6. PMID- 22097491 TI - Microwave-controlled facile synthesis of well-defined PbS hexapods. AB - Controlled synthesis of well-defined PbS nanostructures in terms of size and shape has been strongly motivated by their potential applications ranging from solar photovoltaics to near-infrared optics. Hereby, we report a facile microwave assistant method for ultrafast fabrication of PbS nanostructures, by which uniform PbS hexapods with six arms stretching along six (100) directions of the crystal seeds have been easily synthesized within minutes. Various morphologies including rectangle plates, uniform cubes as well as nanoparticles were obtained by tuning the parameters for the formation of PbS nanocrystals. The results reveal that both concentration and feed ratio of precursors determine the growth of PbS nanocrystals significantly. And higher initial precursor concentration favors the formation of the hexapod structures. The process of crystal growth is monitored through scanning electron microscopy of PbS from different durations of the reaction. This controlled ultrafast synthesis of PbS structures at nanometer and micrometer scale with various morphologies may be promising in large scale fabrication of nanostructures. Based on the systematically study of the growth process, a possible mechanism for the formation of the hexapod-like structure is discussed. PMID- 22097492 TI - Poly(lactic acid)/graphene nanocomposites prepared via solution blending using chloroform as a mutual solvent. AB - Poly(lactic acid) (PLA)/graphene nanocomposites were prepared by direct solution blending of PLA with graphene using chloroform as a mutual solvent. Graphene was prepared by a solution-phase processing followed by thermal reduction, which can be dispersed stably in chloroform for more than one month. Transmission electron microscopy (TEM) was used to examine the quality of the dispersion of graphene in the PLA matrix. The thermal properties and crystallization behavior of the nanocomposites were investigated by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and polar optical microscopy (POM). The results showed that the thermal stability of PLA was significantly improved with a very low loading of graphene and the addition of graphene had a great effect on spherulite morphology of PLA. PMID- 22097493 TI - Biomolecule-assisted green route to Sb2S3 crystals with three-dimensional dandelionlike patterns. AB - This paper describes a simple biomolecule-assisted solvothermal approach to fabricate the three-dimensional (3D) Sb2S3 microsphere with a wealth of novel morphologies in the presence of L-cysteine, which served as both the sulfur source and the directing molecule in the formation of antimony sulfide nanostructures. The effects of different solvents, and polyvinylpyrrolidone (PVP) on the morphology, structure, and phase composition of the as-prepared Sb2S3 products were discussed. The formation of 3D dandelionlike Sb2S3 microsphere was probably via the mechanism of the orientated aggregation growth of the Sb2S3 particles under the complexing action of L-cysteine, and co-action of the surfactant PVP. The absorption spectra of as-prepared 3D dandelionlike Sb2S3 structures show an optical shoulder band gap of 1.81 eV, which is near to the optimum for photovoltaic conversion. PMID- 22097494 TI - In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells. AB - Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals. PMID- 22097495 TI - Preparation of ethosomes and deformable liposomes encapsulated with 5 fluorouracil and their investigation of permeability and retention in hypertrophic scar. AB - With the aim of comparing scar penetration efficiency and retention between ethosomes and deformable liposomes both encapsulated with 5-fluorouracil (5-FU), the 5-FU ethosomal suspensions (5-FU ES, 81.74 +/- 9.37 nm) and the 5-FU Deformable Liposomal Suspensions (5-FU DS, 73.7 +/- 9.45 nm) were prepared respectively by Touitou method and Cevc method, their sizes were determined by Particle Sizer System (PSS), and their entrapment Efficiency (EE) was detected by ultracentrifugation and microcolumn centrifugation. Their transdermal delivery experiments were done in hypertrophic scars in vitro. The permeated amount of 5 FU and retention contents of 5-FU were both calculated by High Performance Liquid Chromatography (HPLC). Fluorescence intensities of ES and DS labeled with Rodanmin 6GO (Rho) were measured by Laser Scanning Microscopy (LSM). The control groups such as the 5-FU and empty ethosomal vesicles (5-FU + EEV), the 5-FU and empty deformable liposomal vesicles (5-FU + EDV) and 5-FU PBS Solution (5-FU Sol) were set up. Results showed that, prepared 5-FU ES was 81.74 +/- 9.37 nm in size, 5-FU DS was 73.7 +/- 9.45 nm, EE of 5-FU ES was 10.95%, EE of 5-FU DS was 15.05%. Within 24 hours, in the group of 5-FU ES, the penetration amount of 5-FU in scar was 14.12 +/- 0.1 microg/mL/cm2, the retention contents of 5-FU was 10.74 +/- 1.17 microg/cm2, and the fluorescence intensity of Rho in hypertrophic scar tissues were 182 +/- 18.3; in the group of 5-FU DS: the penetration amount of 5 FU was 12.35 +/- 1.21 microg/mLcm2; the retention contents of 5-FU was 17.48 +/- 0.82 microg/cm2, and the fluorescence intensity of Rho was 241.45 +/- 7.63; there existed statistical difference between penetration amount in the group of 5-FU ES and that in the group of 5-FU DS as well as control groups (P < 0.05, P < 0.01), the penetration amount in the group of ES is markedly higher than DS group or control groups. Conversely, the retention contents of 5-FU and the fluorescence intensity of Rho in DS group were higher than those in ES group and control groups (P < 0.05, P < 0.01). In conclusion, both ES and DS could deliver 5-FU into the hypertrophic scars effectively. ES has better permeability of 5-FU than DS, DS has higher entrapment efficiency of 5-FU, and more 5-FU deposition in hypertrophic scar than ES. We should select ES or DS encapsulated with 5-FU according to clinical demand for hypertrophic scar therapy. PMID- 22097496 TI - Toxicity of nano gamma alumina to neural stem cells. AB - Nano alumina, one of the most important nanomaterials, is widely used in diverse areas. It was reported that nano alumina could cross the blood brain barrier to enter the brain. Considering aluminum accumulation in brain is closely related to many neural diseases. We studied the neural toxicity of four nano gamma-alumina samples by using neural stem cells (NSCs) C17.2 as a model. We find that the toxicity of nano gamma-alumina is pretty low, though these alumina particles are easily internalized by cells. The loss of cell viability and membrane integrity are dose-dependent and sample-dependent after alumina exposure. At concentrations lower than 100 microg/mL, no significant toxicity is observed for all alumina samples. When the concentration reaches 200 microg/mL, alumina treated cells begin to loss their activities. No culture period effect (up to 3 days) is observed. Very tiny soluble aluminum and the absorption of culture medium ingredients onto alumina particles do not affect the cell viability. Intracellular reactive oxygen species generation may contribute to the cytotoxicity of alumina particles at high concentration, but it does not induce the apoptosis of NSCs. PMID- 22097497 TI - Interaction between fullerenes and single-wall carbon nanotubes: the influence of fullerene size and electronic structure. AB - A series of fullerenes and endohedral metallofullerenes peapods have been synthesized by supercritical method in high filling rate. The interaction between SWNTs and various kinds of fullerenes (C60, C70, C78, C84) and metallofullerenes (Gd@C82, Er@C82, Ho@C82, Y@C82) has been further investigated. The slight blue shift of G-band in Raman spectra with respect to pristine SWNTs was attributed to the charge transfer from SWNTs to fullerenes cage. The obvious RBM shift strongly depended on the distance between the inner wall of the SWNTs and the fullerene cage and also partly associated with the electronic structure of the fullerene. These results indicated that the interaction between fullerenes and SWNTs, which was considered to be the van de walls interaction, can be influenced by the cage size and the kind of fullerenes. PMID- 22097498 TI - Nano-silver mediated polymerization of pyrrole: synthesis and gas sensing properties of polypyrrole (PPy)/Ag nano-composite. AB - Thermal polymerization of pyrrole was performed using silver nitrate as source of silver ions followed by its conversion to Polypyrrole (PPy)/Ag nano-comoposites without using any external oxidizing agent or solvent. The formation of PPy was monitored by UV-Visible absorption spectroscopy showing a band at approximately 464 nm. XRD measurement confirmed characteristic peaks for face centered cubic (fcc) silver and presence of PPy at 2 theta of approximately 23 degrees suggesting the formation of PPy/Ag nanocomposite. Transmission electron microscopy (TEM) images showed non-aggregated spherical Ag nano-particles of about 5-10 nm. PPy/Ag thick film acts as a NH3 sensor at 100 degrees C, a H2S sensor at 250 degrees C and CO2 sensor at 350 degrees C. The thick films showed capability to recognize various gases at different operating temperature. PMID- 22097499 TI - Nanostructured H(3+x)PW(12-x)NbxO40 (x = 0-3) Keggin heteropolyacid catalysts. AB - Nanostructured H(3+x)PW(12-x)NbxO40 (x = 0, 1, 2, 3) Keggin heteropolyacid (HPA) catalysts were investigated by scanning tunneling microscopy (STM) and tunneling spectroscopy to probe their redox property and oxidation catalysis. STM image showed that the HPAs formed two-dimensional well-ordered monolayer arrays on graphite surface. In tunneling spectra of the HPAs deposited on graphite, they exhibited a distinctive current-voltage behavior referred to as negative differential resistance (NDR). NDR peak voltage measured atop HPA molecule was then correlated with reduction potential and absorption edge energy determined by electrochemical method and UV-visible spectroscopy, respectively. It was revealed that NDR peak voltage of the HPAs appeared at less negative voltage with increasing reduction potential and with decreasing absorption edge energy. In order to correlate NDR peak voltage of H(3+x)PW(12-x)NbxO40 Keggin HPAs with oxidation catalysis, oxidative dehydrogenation of isobutyraldehyde to methacrolein was carried out as a model reaction. NDR peak voltage of the HPAs appeared at less negative voltage with increasing yield for methacrolein. PMID- 22097500 TI - TiO2 and SnO2 magnetic nanocomposites: influence of semiconductors and synthetic methods on photoactivity. AB - A number of reports have been published on use of TiO2 in thin films, magnetic nanocomposites, or heterostructures such as TiO2/Ag and TiO2/SnO2, as catalysts for water decontamination. Hence, semiconductor materials such as SnO2, associated with TiO2 in such nanocomposites, should be assessed in depth for such applications, especially those involving complex structures, such as magnetic photocatalytic nanocomposites. The present study describes the synthesis, characterization and testing of the photocatalytic potential of TiO2 or SnO2 magnetic nanocomposites obtained by the polymeric precursor and the hydrolytic sol-gel methods. The nanocomposites TiO2/CoFe2O4 and SnO2/CoFe2O4 were synthesized from polymeric precursors while TiO2/Fe3O4 and SnO2/Fe3O4 were synthesized by the hydrolytic sol-gel method. The materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (FEG/SEM) and transmission electron microscopy (TEM). The photocatalytic potentials were evaluated by rhodamine B dye photodegradation under UV-C radiation. Compared to SnO2, the nanocomposites with a coating of TiO2 were found to show better photocatalytic activity, but the SnO2 magnetic nanocomposites showed some photocatalytic activity, even though SnO2 is reported to be inactive for these purposes. As for the synthesis method, the nanocomposites obtained from polymeric precursors had smaller surface areas, but higher photocatalytic activity, than those obtained by the hydrolytic sol-gel method. This observation was attributed to the higher crystallinity and a more active surface resulting from calcination of the polymeric precursor material. PMID- 22097501 TI - Crystallization, mechanical properties, and controlled enzymatic degradation of biodegradable poly(epsilon-caprolactone)/multi-walled carbon nanotubes nanocomposites. AB - Biodegradable poly(epsilon-caprolactone) (PCL)/multi-walled carbon nanotubes containing carboxylic groups (f-MWNTs) nanocomposites were prepared via simple melt compounding at low f-MWNTs loading in this work. Scanning and transmission electron microscopy observations indicate a homogeneous and fine distribution of f-MWNTs throughout the PCL matrix. The effect of low f-MWNTs loading on the crystallization, mechanical properties, and controlled enzymatic degradation of PCL in the nanocomposites were studied in detail with various techniques. The experimental results indicate that the incorporation of f-MWNTs enhances both the nonisothermal crystallization peak temperature and the overall isothermal crystallization rate of PCL in the PCL/f-MWNTs nanocomposites relative to neat PCL; moreover, the incorporation of a small quantity of f-MWNTs has improved apparently the mechanical properties of the PCL/MWNTs nanocomposites compared to neat PCL. The enzymatic degradation of neat PCL and the PCL/f-MWNTs nanocomposites at low f-MWNTs loading was studied in detail. The variation of weight loss with enzymatic degradation time, the surface morphology change, the reduced film thickness, the appearance of f-MWNTs on the surface of the films, and the almost unchanged molecular weight after enzymatic degradation suggest that the enzymatic degradation of neat PCL and the PCL/f-MWNTs nanocomposites may proceed via surface erosion mechanism. The presence of f-MWNTs reduces the enzymatic degradation rate of the PCL matrix in the nanocomposites compared with that of the pure PCL film. PMID- 22097502 TI - Synthesis and characterization of CLEA-lysozyme immobilized PS/PSMA nanofiber. AB - Using 0.2% glutaraldehyde as the cross-linker, lysozyme was covalently immobilized onto electrospun polystyrene/poly(styrene-co-maleic anhydride) (PS/PSMA) nanofibers as cross-linked enzyme aggregates (CLEA). The lysozyme capacity of PS/PSMA nanofibers under optimal condition was 57.6 mg/g of nanofibers. Various parameters were used to evaluate the stability of the immobilized CLEA-lysozyme. Compared to free enzyme, the immobilized CLEA-lysozyme exhibited its optimal enzymatic activity at higher temperature and pH. The immobilized CLEA-lysozyme maintained more than 78% of its initial activity during 30 days of storage period. Additionally, the immobilized CLEA-lysozyme presented a high antibacterial activity against Staphylococcus aureus. The durability determinations of such nanofibers showed 90.3% retention of the initial lysozyme activity after 80 consecutive reuses, and 81.2% of bacteriostasis ratio after 10 cycles. The results of this study suggest that CLEA-lysozyme immobilized nanofiber which can stabilize its enzymatic activity through cross-linking immobilization can be beneficial for various antibacterial processes. PMID- 22097503 TI - Tough yttria-stabilized zirconia ceramic by low-temperature spark plasma sintering of long-term stored nanopowders. AB - Weakly agglomerated 1.75 and 3 mol% yttria stabilized zirconia nanopowders were used in this study after six years of storage in vacuum-processed plastic containers. The proper storage conditions of the Y-TZP nanopowders avoided the hard agglomeration. Untreated and bead-milled nanopowders were used to obtain dense ceramics by slip casting and subsequent low-temperature sintering. Fully dense nanostructured 1.75Y-TZP and 3Y-YZP ceramics with and without doping of 1 wt% Al2O3 were produced by an optimized spark plasma sintering (SPS) technique at the temperatures of 1050-1150 degrees C at a pressure of 100 MPa. The SPS has revealed the clear advantage of consolidation of the weakly agglomerated nanopowders without preliminary deagglomeration. The Vickers hardness of both the low-temperature and spark plasma sintered samples was found to lie in the range of 10.98-13.71 GPa. A maximum fracture toughness of 15.7 MPa m(1/2) (average 14.23 MPa m(1/2)) was achieved by SPS of the 1.75Y-TZP ceramic doped with 1 wt% Al2O3 whereas the toughness of the 3Y-TZP ceramics with and without alumina doping was found to vary between 3.55 and 5.5 MPa m(1/2). PMID- 22097504 TI - Ni2+ doped indium oxide nanocubes: doped contents inducing transferring of their intrinsic magnetisms. AB - A series of Ni2+ doped indium oxide nanocubes with different Ni2+ contents (nominally from 3 at.% to 20 at.%) were prepared by direct solvothermal method. We found that the highest Ni2+ doped percentage was 20 at.% in the experiment and crystalline sizes of these Ni2+ doped indium oxide specimens linearly increased with increments of doped contents and then decreased. Meanwhile, their magnetisms were also transferred from ferromagnetism to paramagnetic properties due to the stronger Ni-O-Ni paramagnetic chemical bonds. HRTEM, SAED and XRD further confirmed their magnetic properties were intrinsic and not caused by second impure phases. PMID- 22097505 TI - Surface nanostructuring of boron-doped diamond films and their electrochemical performance. AB - Uniform and vertically aligned nanocone and nanopillar arrays were successfully constructed on heavily boron-doped nanocrysatlline diamond films by carrying out bias-assisted reactive ion etching in hydrogen/argon plasmas. The electrochemical properties of the nanostructured boron-doped diamond films were investigated by cyclic voltammetry using 1 mM [Fe(CN)6](3-/4-) as redox couple. Compared to the planar boron-doped nanocrystalline diamond film electrode, the surface nanostructuring of boron-doped diamond film electrodes demonstrate enhanced sensitivity due to their enlarged electro-active surface areas. The results indicated that boron-doped diamond nanocones and nanopillars are promising electrode materials which benefit to improve the efficiency, sensitivity and reproducibility of biomedical and chemical sensors. PMID- 22097506 TI - From nanotubes to nano-cocoons with coiled pore channels. AB - Silica nanotubes with coiled pore channels and hollow spheres with coiled or concentric circular pore channels have been prepared using the self-assemblies of chiral cationic amphiphiles as templates. However, the relationship among these morphologies and pore architectures has not been well studied. For a better understanding the relationship, silica nanostructures were systematically prepared by tuning the reaction conditions. With increasing the stirring rate, silica nanotube with coiled pore channels changed to linked nano-cocoon with coiled pore channels. With increasing the concentration of the reaction mixture, the morphology changed from sphere to linked cocoon, and then to nanorod with lamellar mesopores on the surface. Transmission electron microscopy images taken after different reaction times indicated a cooperation mechanism. PMID- 22097507 TI - Comparison studies between hydrogenation and oxidation of MWNTs followed by acid treatment. AB - MWNTs obtained using iron catalyst and ethylene as a carbon source were submitted to a purification procedure. To purify these materials from amorphous carbon two parallel methods--based on either hydrogen or air treatment--were applied. At the second purification stage iron particles were removed using 1 M or 5 M nitric or hydrochloric acids. The phase composition of the samples was determined using X ray diffraction method. The sample morphology was characterized using a high resolution transmission electron microscopy. The relative fraction of impurities in the samples was estimated by Raman spectroscopy and the quantitative analysis of metal impurity content was validated by means of thermogravimetric analysis. PMID- 22097508 TI - Enhanced mechanical properties of electrospun nano-fibers through NaCl mediation. AB - Electrospun (ES) nano-scale polymer fibers are known to exhibit lower Young's modulus and strength than their bulk counterpart. We have discovered that minute additions of sodium chloride (NaCl) during the preparation stage of ES polymethyl methacrylate (PMMA) fibers raises the fiber mechanical properties in a significant way, nearly up to bulk values, over a range of diameters. NaCl induced electrical effects leading to enhanced molecular alignment during nano fiber formation is the most likely explanation for this synergistic effect. Moreover, beyond the now-recognized rise in Young's modulus values, we observed that the strength and tensile toughness of the ES fibers also significantly increase at progressively smaller diameters. PMID- 22097509 TI - Mono-disperse silver quantum dots modified formvar film. AB - Formvar films were treated with different doses of silver ions implantation. The implanted silver ions were found to form silver quantum dots (AgQDs) uniformly distributed in the formvar films. While density of the AgQDs increases as the implantation dose increases, their sizes are not sensitive to the dose. It was found that the formvar films implanted with AgQDs have excellent bacteria killing capability. The same implantation approach can also be extended for application in other matrices. As an example, ZnS nanoribbon was implanted with the same approach to obtain uniformly distributed AgQDs with monodispersed size. PMID- 22097510 TI - Facile microwave-combustion synthesis of wurtzite CdS nanoparticles. AB - In this study we first report microwave-combustion synthesis of faceted CdS nanoparticles by using cadmium thiocyanate complex as a single source precursor. This is the first example of a metal-thiocyanate (M-SCN) complex being used as a source for metal sulfides (M-S) preparation in a microwave-combustion process. The synthesized CdS was characterized using X-ray diffraction (XRD), field mission scanning electron microscopy (FE-SEM), and high-resolution transmission electron microscopy (HR-TEM). The by-product assisted combustion synthesis yields CdS nanoparticles with the mixtures of octahedral geometries, hexagonal, and triangle plate morphologies and the sizes were found to be 100 nm to 5 microm. The XRD patterns imply the formation of well crystallized wurtzite CdS. The influence of cadmium and sulfur precursors and microwave irradiation time on the morphology of CdS nanoparticle was also investigated. The cadmium and sulfur precursors strongly influenced the CdS morphology and increasing the microwave irradiation time and intensity has no effect on the CdS morphology. In addition, a plausible mechanism of CdS nanoparticle formation has been proposed in this research. PMID- 22097511 TI - Metalcones: hybrid organic-inorganic films fabricated using atomic and molecular layer deposition techniques. AB - Hybrid organic-inorganic films can be deposited using atomic layer deposition (ALD) and molecular layer deposition (MLD) techniques. A special set of hybrid organic-inorganic films based on metal precursors and various organic alcohols yields metal alkoxide films that can be described as "metalcones." Many metalcone films are possible such as the "alucones" and "zincones" based on the reaction of trimethylaluminum and diethylzinc, respectively, with various organic alcohols such as ethylene glycol (EG). This paper reviews the previous work on metalcone MLD and discusses a variety of new metalcone systems. "Titanicones" are grown using TiCl4 and glycerol or EG and "zircones" are grown using zirconium tetra tert-butoxide and EG. In addition, the organic alcohol can also be varied to change the properties within one metalcone family. For example, the glycerol triol precursor allows for more cross-linking and higher toughness in alucones than the EG diol precursor. Alloys can also be formed by combining metalcone MLD and metal oxide ALD. By varying the relative number of cycles of MLD and ALD, the composition and properties of the hybrid organic-inorganic films can be tuned from pure metalcone MLD to pure metal oxide ALD. PMID- 22097512 TI - Synthesis of active carbon-based catalysts by chemical vapor infiltration for nitrogen oxide conversion. AB - Direct reduction of nitrogen oxides is still a challenge. Strong efforts have been made in developing noble and transition metal catalysts on microporous support materials such as active carbons or zeolites. However, the required activation energy and low conversion rates still limit its breakthrough. Furthermore, infiltration of such microporous matrix materials is commonly performed by wet chemistry routes. Deep infiltration and homogeneous precursor distribution are often challenging due to precursor viscosity or electrostatic shielding and may be inhibited by pore clogging. Gas phase infiltration, as an alternative, can resolve viscosity issues and may contribute to homogeneous infiltration of precursors. In the present work new catalysts based on active carbon substrates were synthesized via chemical vapor infiltration. Iron oxide nano clusters were deposited in the microporous matrix material. Detailed investigation of produced catalysts included nitrogen oxide adsorption, X-ray diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Catalytic activity was studied in a recycle flow reactor by time resolved mass spectrometry at a temperature of 423 K. The infiltrated active carbons showed very homogeneous deposition of iron oxide nano clusters in the range of below 12 to 19 nm, depending on the amount of infiltrated precursor. The specific surface area was not excessively reduced, nor was the pore size distribution changed compared to the original substrate. Catalytic nitrogen oxides conversion was detected at temperatures as low as 423 K. PMID- 22097513 TI - Remote plasma processing of sapphire substrates for deposition of TiN and TiO2. AB - The paper uses remote plasma assisted deposition, oxidation and nitridation processes for depositing thin films of metallic TiN on crystalline sapphire (0001) substrates. These films on sapphire substrates are being studied as window materials for high power radio frequency (RF) power tubes. A sequence of four process steps has been performed in a reactor chamber that isolates the deposition and surface-processing chamber from the plasma generation region. The chamber is part of an ultra-high-vacuum (UHV) compatible multi-chamber cluster in which the sequence of four process steps can be interrupted after each step, and surface chemistry changes can be identified by in-line Auger electron spectroscopy (AES). The four process steps, performed after an ex-situ chemical clean and blow-dry in nitrogen gas, are (i) a remote plasma-assisted oxidation (RPAO) in which surface contaminants including adventitious carbon are removed; (ii) a remote plasma-assisted nitridation (RPAN) process which forms a superficial layer of generic AION used to increase surface adhesion of the TiN films; (iii) a remote plasma-enhanced chemical-vapor deposition (RPECVD) process for deposition of 2 to 5 nm thick TiN films, and finally (iv) a second RPAN step that increases the ratio of Ti-N bonding in the TiN films with respect to adventitious O-atom incorporation from the Ti precursor, Ti tetra-butoxide. PMID- 22097514 TI - Formation of fractal structures from silicon dioxide nanoparticles synthesized by RF atmospheric pressure plasma enhanced chemical vapor deposition. AB - Fractal structures were formed on silicon substrates from SiO2 nanoparticles homogeneously synthesized in low temperature atmospheric pressure plasma from tetraethoxysilane (TEOS). RF discharge (power absorbed was about 10 W) sustained between two parallel mesh electrodes was used to generate plasma. The average size of nanoparticles was in the range of 8-20 nm and was determined by process parameters. The obtained products were analyzed by SEM (scanning electron microscopy) and XPS (X-ray photoelectron spectroscopy). Values of fractal dimension parameter of bidimensionals agglomerates formed on the substrate surface from nanoparticles were calculated with the use of Gwyddion and others. It was found that values of this parameter of the deposited structures varied in the range of 1.48-2 and were determined by combination of the process parameters. An empirical model explaining mechanism of the fractal structures formation and variation of the fractal dimension parameter with the process parameters was proposed. PMID- 22097515 TI - Remote plasma enhanced chemical deposition of non-crystalline GeO2 on Ge and Si substrates. AB - Non-crystalline GeO2 films remote were plasma deposited at 300 degrees C onto Ge substrates after a final rinse in NH4OH. The reactant precursors gas were: (i) down-stream injected 2% GeH4 in He as the Ge precursor, and (ii) up-stream, plasma excited O2-He mixtures as the O precursor. Films annealed at 400 degrees C displayed no evidence for loss of O resulting in Ge sub-oxide formation, and for a 5-6 eV mid-gap absorption associated with formation of GeOx suboxide bonding, x < 2. These films were stable in normal laboratory ambients with no evidence for reaction with atmospheric water. Films deposited on Ge and annealed at 600 degrees C and 700 degrees C display spectra indicative of loss of O-atoms, accompanied with a 5.5 eV absorption. X-ray absorption spectroscopy and many electron theory are combined to describe symmetries and degeneracies for O vacancy bonding defects. These include comparisons with remote plasma-deposited non-crystalline SiO2 on Si substrates with SiON interfacial layers. Three different properties of remote plasma GeO2 films are addressed comparisons between (i) conduction band and band edge states of GeO2 and SiO2, and (ii) electronic structure of O-atom vacancy defects in GeO2 and SiO2, and differences between (iii) annealing of GeO2 films on Ge substrates, and Si substrates passivated with SiON interfacial transition regions important for device applications. PMID- 22097516 TI - Nanosynthesis of tunable composite materials by room-temperature pulsed focused electron beam induced chemical vapour deposition. AB - Hydrocarbons inherently present in standard high-vacuum scanning electron microscopes can be favorably used for co-deposition with functional molecules injected into the chamber. By varying the beam exposure pulse time the carbon content incorporated into the deposit can be tuned. In the particular case when the hydrocarbons are provided by surface diffusion, the composition depends also on the size of the final deposits. This dependency can be used as an additional parameter, besides the beam pulse time, in order to tune the metal/matrix ratio and to obtain new nanoscale materials with tailored physical properties. We present and discuss experimental results on composition tunability by pulsed electron-beam deposition for the two-adsorbate system Co2(CO)8/hydrocarbon and their use in fabricating Hall nanosensors of cobalt-carbon nanocomposite material with enhanced magnetic sensitivity and high magnetic spatial resolution. PMID- 22097517 TI - Multiscale analysis of silicon carbide-chemical vapor deposition process. AB - A kinetic study, which was performed by using multi-scale (a macro and a micro scale) analysis, is presented in order to determine the reaction mechanism of the chemical vapor deposition (CVD) of silicon carbide (SiC) from CH3SiCl3 (MTS)/H2 gaseous mixture. The multi-scale analysis provides two well-defined reaction fields, corresponding to the flat substrates placed in a hot wall reactor and micro trenches on the substrate surface, with centimeter and submicron characteristic length scales, respectively. The microcavity method is a micro scale analysis used to study the relative contributions of gas-phase and surface reactions to the SiC growth, and to determine the sticking probability of growth species in CVD reaction systems. From the macro-scale analysis, activation energy of the growth rate was estimated to be 43.0 kcal/mol at the up-stream part and the sticking probability was estimated to be 9.5 x 10(-7) at 1273 K and 6.8 x 10( 6) at 1373 K. On the other hand, we examined a sticking probability (eta) and the reaction mechanism by using the microcavity method. From the micro-scale analysis, we found that at least two growth species, a stable intermediate 1 (eta 1, = 1.3 x 10(-3) at 1273 K and 4.5 x 10(-3) at 1373 K) and a highly active intermediate 2 (eta 2 = 2.0 x 10(-1) at 1273 K and 5.4 x 10(-1) at 1373 K), are formed as byproducts of the gas-phase reaction. Activation energy of the sticking probability was 43.9 kcal/mol in the case of the intermediate 1 and 34.5 kcal/mol in the case of the intermediate 2. We could also confirm that the source precursor, MTS, was not the film growth species. Another analytical model based on Monte Carlo simulations correlates the film profile in the microcavity to the sticking probability of the deposition species. The combination of these two analysis techniques presents an overall picture of the reaction scheme. PMID- 22097518 TI - Atomic layer deposition ultra-barriers for electronic applications-strategies and implementation. AB - We show that Al2O3 thin films, grown by atomic layer deposition (ALD) on polyester, are ultrabarriers with moisture permeation <10(-5) g-H2O/m2-day, as determined after aging for more than three years. We present evidence that the mechanism for gas permeation in ALD Al2O3 films is not due to pinholes, but that the onset of permeation occurs abruptly, analogous to electrical breakdown in oxide thin films. We show that the permeation onset time increases for thicker Al2O3 films and higher ALD process temperature, for which the hydrogen defect concentration in Al2O3 films is less. Further, we show that mild plasma treatment of the polyester, prior to ALD deposition of Al2O3, makes the surface more hydrophilic and reduces moisture permeation compared to an untreated surface. Similarly, ALD deposition on the bare or non-slip side of the polyester film is preferred for low permeation. PMID- 22097519 TI - Comparison of characteristics of fluorine doped zinc and gallium tin oxide composite thin films deposited on stainless steel 316 bipolar plate by electron cyclotron resonance-metal organic chemical vapor deposition for proton exchange membrane fuel cells. AB - In order to replace the brittle graphite bipolar plates currently used for the PEMFC stack, coated SUS 316 was employed. As a metallic bipolar plate, coated SUS 316 can provide higher mechanical strength, better durability to shocks and vibration, less permeability, improved thermal and bulk electrical conductivity, as well as being thinner and lighter. To enhance the interfacial contact resistance and corrosion resistance of SUS 316, the deposition of GTO:F and ZTO:F composite films was carried out by ECR-MOCVD. The surface morphology of the films consisted of tiny elliptically shaped grains with a thickness of 1 microm. The corrosion current for GTO:F was 0.13 Acm(-2) which was much lower than that of bare SUS 316 (50.16 Acm(-2)). The GTO:F coated film had the smallest corrosion current due to the formation of a tight surface morphology with very few pin holes. The GTO:F coated film exhibited the highest cell voltage and power density due to its lower ICR values. PMID- 22097520 TI - An automatic system using mobile-agent software to model the calculation process of a chemical vapor deposition film deposition simulator. AB - We have developed an automatic modeling system for calculation processes of the simulator to reproduce experimental results of chemical vapor deposition (CVD), in order to decrease the calculation cost of the simulator. Replacing the simulator by the mathematical models proposed by the system will contribute towards decreasing the calculation costs for predicting the experimental results. The system consists of a mobile agent and two software resources in computer networks, that is, generalized modeling software and a simulator reproducing cross-sections of the deposited films on the substrates with the micrometer- or nanometer-sized trenches. The mobile agent autonomously creates appropriate models by moving to and then operating the software resources. The models are calculated by partial least squares regression (PLS), quadratic PLS (QPLS) and error back propagation (BP) methods using artificial neural networks (ANN) and expresses by mathematical formulas to reproduce the calculated results of the simulator. The models show good reproducibility and predictability both for uniformity and filling properties of the films calculated by the simulator. The models using the BP method yield the best performance. The filling property data are more suitable to modeling than film uniformity. PMID- 22097521 TI - Textured tetragonal ZrO2 film grown on (100) silicon surface by DLI metal-organic chemical vapor deposition. AB - Zirconia (ZrO2) thin films with micronic layer thickness are deposited on Si(100) substrates by MOCVD in a cold wall reactor using direct injection (DLI-CVD) process with Zr2(OiPr)6(thd)2 precursor diluted in cyclohexane. The effects of experimental parameters such as substrate's temperature, injection frequency, oxygen partial pressure in the reactive chamber and deposition duration of the process are investigated in order to produce a strongly textured tetragonal ZrO2 film. The films crystalline structure and crystallite size (several nm) are identified by Grazing incidence X-ray diffraction (GIXRD); the microstructure and morphology are observed with the use of FEG-SEM. GIXRD patterns showed the predominance of nano-crystallized tetragonal phase (or cubic) in the films. Pole figures have been analysed for both {111}(t-c) and {200}(t-c) planes in order to evaluate the relationship binding the preferential crystallographic orientation to the column-like growth structure. Besides, the internal stresses levels (with the use of sin2 psi method) within zirconia layers varied from a compressive to a tensile state depending on the experimental deposition conditions and are related to phase orientation and/or transformation into monoclinic one. It is demonstrated that high temperature, low pressure and low deposition time enhanced the tetragonal phase quality that became highly (200)t textured. PMID- 22097522 TI - Electrochromic and optical study of atmospheric pressure chemical vapour deposition MoO3-Cr2O3 films. AB - Electrochromism (EC) is a phenomenon in which materials are able to change their optical properties in a reversible and persistent way under the action of a voltage pulse. The studied MoO3-Cr2O3 films are obtained by atmospheric pressure CVD. Mixing MoO3 films with Cr2O3 is expected to enhance optical transparency and to modulate electrochromic properties of MoO3 films. In the present work, the study is focused on the morphological, structural and optical properties of MoO3 Cr2O3 films as a function of annealing temperatures. Raman spectroscopy and optical spectrophotometry are used for the film characterization. The mixed oxide films obtained on ordinary glass substrates show transmittance values in the range of 70-80%. Surface morphology is analyzed by SEM and AFM methods. The microanalysis of MoO3-Cr2O3 films reveals uniform distribution of the elements, which is a sign of homogeneous structure. PMID- 22097523 TI - In-line silicon epitaxy for photovoltaics using a continous chemical vapour deposition reactor. AB - Thin film solar cell techniques can effectively reduce the costs for photovoltaic solar power. However, most of these techniques still have the disadvantage of a comparatively low efficiency. One way to realize a thin film solar cell concept with high efficiency potential is the crystalline silicon thin-film (cSiTF) concept. Following the high-temperature approach, this concept is based on a silicon epitaxy process. This paper reports the current status of the development of a high throughput epitaxy tool at Fraunhofer ISE and presents first results. Also presented is the development of a simulation tool which is a virtual image of the real setup in order to forecast save deposition conditions. The presented epitaxy tool is the ConCVD (Continuous Chemical Vapour Deposition), in which an improved reactor setup has been installed, based on the experience gained so far. To provide insight into upcoming further advances, the industrial scale epitaxy tool ProConCVD is presented as well. PMID- 22097524 TI - Real-time ellipsometric characterization of the initial growth stage of poly(3,4 ethylene dioxythiophene): poly(styrene sulfonic acid) films by electrospray deposition. AB - Kinetic spectroscopic ellipsometry have been used to study the initial growth stage of poly(3,4-polyethylene dioxythiophene):poly(styrenesulfonic acid)(PEDOT:PSS) films by the electrospray deposition (ESD) method. The real-time spectra analysis revealed that the surface overlayer decreased in thickness once the first bulk layer monolayer was formed, indicating a smoothening effect as the nucleation-related microstructure coalesced into the bulk layer. Once the coalescence was completed and the nucleation-induced surface roughness layer was stabilized, the underlying bulk layer increased linearly with time. These results originate from the degrees of the evaporation of solvent material during the transferring the precursors to the surface and/or of the diffusion of deposition precursors after sticking at the growing surface. PMID- 22097525 TI - Surface modification of poly(3,4-ethylene dioxthiophene):poly(styrene sulfonic acid) (PEDOT:PSS) films by atmospheric-pressure argon plasma for organic thin film solar cells. AB - Highly-conductive poly(3,4-ethylene dioxythiophene):poly(styrene sulfonic acid) (PEDOT:PSS) films obtained by the addition of dimethylsulfoxide (DMSO) and the argon plasma exposure were used as a transparent conductive anode (TCA) for copper-phthalocyanine (CuPc)/C60 organic thin-film solar cells (OSCs). The CuPc/C60 OSCs on as-grown DMSO added PEDOT:PSS layer showed a power efficiency of 0.6%, whereas it was improved markedly to 1.34% after the atmospheric-pressure argon plasma exposure, which was comparable to that formed on indium-tin-oxide layer. Effects of the DMSO addition and the argon plasma exposure in the spin coated PEDOT:PSS films is demonstrated in terms of the in-depth characterization of optical and electrical properties. PMID- 22097526 TI - SiGe epitaxy on a 300 mm batch furnace. AB - This work reports the feasibility of silicon and silicon germanium epitaxy using an ASM A412(TMa) LPCVD all quartz, hot wall, vertical batch furnace reactor using 100 wafer product loads. The very same furnace can be used for 25 wafer and 200 wafer load size, without any hardware changes, dependant on production needs. Following this approach a significant cost reduction for epitaxy in 300 mm high volume manufacturing is possible and enables new applications. The native oxide of the substrate was removed by wet chemical cleaning with time coupling of less than 1 h and subsequent in-situ low pressure hydrogen anneal prior to Si or SiGe deposition. The epitaxial layers were grown using silane and germane. The Si and SiGe layers have been characterized with ToFSIMS, XRD, Raman, AFM and TEM confirming excellent crystalline quality, layer thickness and within wafer SiGe stoichiometry uniformity. PMID- 22097527 TI - An automatic modeling system of the reaction mechanisms for chemical vapor deposition processes using real-coded genetic algorithms. AB - The identification of appropriate reaction models is very helpful for developing chemical vapor deposition (CVD) processes. In this study, we have developed an automatic system to model reaction mechanisms in the CVD processes by analyzing the experimental results, which are cross-sectional shapes of the deposited films on substrates with micrometer- or nanometer-sized trenches. We designed the inference engine to model the reaction mechanism in the system by the use of real coded genetic algorithms (RCGAs). We studied the dependence of the system performance on two methods using simple genetic algorithms (SGAs) and the RCGAs; the one involves the conventional GA operators and the other involves the blend crossover operator (BLX-alpha). Although we demonstrated that the systems using both the methods could successfully model the reaction mechanisms, the RCGAs showed the better performance with respect to the accuracy and the calculation cost for identifying the models. PMID- 22097528 TI - Growth of TiO2 with thermal and plasma enhanced atomic layer deposition. AB - We show a comparative study of the TiO2 ALD with TTIP and either O2 or O2-plasma on Si/SiO2 substrates. In particular we compare the surface morphology and crystalline phase by means of Atomic Force Microscopy (AFM), X-ray Photoelectron Spectroscopy (XPS) and X-ray Absorption Spectroscopy (XAS) for different O2 plasma procedures upon changing the time between cycles and the N2-purging pressure. The AFM images show that already these parameters may induce structural changes in the TiO2 films grown by ALD, with the formation of crystallites with average lateral width varying between 15 and 80 nm. By means of XAS we also found that the crystallites have mixed anatase and rutile crystalline phases and that smaller crystallites have a greater rutile component than the larger ones. PMID- 22097529 TI - Kinetics of SiHCl3 chemical vapor deposition and fluid dynamic simulations. AB - Though most of the current silicon photovoltaic technology relies on trichlorosilane (SiHCl3) as a precursor gas to deposit Si, only a few studies have been devoted to the investigation of its gas phase and surface kinetics. In the present work we propose a new kinetic mechanism apt to describe the gas phase and surface chemistry active during the deposition of Si from SiHCl3. Kinetic constants of key reactions were either taken from the literature or determined through ab initio calculations. The capability of the mechanism to reproduce experimental data was tested through the implementation of the kinetic scheme in a fluid dynamic model and in the simulation of both deposition and etching of Si in horizontal reactors. The results of the simulations show that the reactivity of HCl is of key importance in order to control the Si deposition rate. When HCl reaches a critical concentration in the gas phase it starts etching the Si surface, so that the net deposition rate is the net sum of the adsorption rate of the gas phase precursors and the etching rate due to HCl. In these conditions the possibility to further deposit Si is directly related to the rate of consumption of HCl through its reaction with SiHCl3 to give SiCl4. The proposed reaction mechanism was implemented in a 3D fluid dynamic model of a simple Siemens reactor. The simulation results indicate that the proposed interpretation of the growth process applies also to this class of reactors, which operate in what can be defined as a mixed kinetic-transport controlled regime. PMID- 22097530 TI - A sub-atmospheric chemical vapor deposition process for deposition of oxide liner in high aspect ratio through silicon vias. AB - The formation of a Through Silicon Via (TSV) includes a deep Si trench etching and the formation of an insulating layer along the high-aspect-ratio trench and the filling of a conductive material into the via hole. The isolation of the filling conductor from the silicon substrate becomes more important for higher frequencies due to the high coupling of the signal to the silicon. The importance of the oxide thickness on the via wall isolation can be verified using electromagnetic field simulators. To satisfy the needs on the Silicon dioxide deposition, a sub-atmospheric chemical vapor deposition (SA-CVD) process has been developed to deposit an isolation oxide to the walls of deep silicon trenches. The technique provides excellent step coverage of the 100 microm depth silicon trenches with the high aspect ratio of 20 and more. The developed technique allows covering the deep silicon trenches by oxide and makes the high isolation of TSVs from silicon substrate feasible which is the key factor for the performance of TSVs for mm-wave 3D packaging. PMID- 22097531 TI - Chemical activity of oxygen atoms in the magnetron sputter-deposited ZnO films during film growth. AB - The role of oxygen atoms in the growth of magnetron sputter-deposited ZnO films was studied in a deposition and post-deposition study in which the deposition of a several-nanometer-thick ZnO layer altered with an exposure to an O2/Ar mixed plasma, i.e., a layer-by-layer (LbL) technique. The film crystallization was promoted by suppressing the oxygen vacancy and interstitial defects by adjusting the exposure conditions of the O2/Ar plasma. These findings suggest that the chemical potential of the oxygen atom influences the film crystallization and the electronic state. The diffusion and effusion of oxygen atoms at the growing surface have an effect similar to that of thermal annealing, promoted film crystallization and the creation and the annihilation of oxygen- and zinc-related defects. The role of oxygen atoms reaching the growing film surface is discussed in terms of chemical annealing and a possible oxygen diffusion mechanism is proposed. PMID- 22097532 TI - Determination of the surface diffusion coefficient and the residence time of adsorbates via local focused electron beam induced chemical vapour deposition. AB - In this paper we present a model for local gas assisted focused electron beam induced deposition which allows estimating the surface diffusion coefficient and the residence time of volatile precursor adsorbates. Elaborating the existing continuum model for one adsorbate species and using a novel set of parameters we simplified the differential equation describing the dynamics of this process. We will show that stationary exposure experiments do not allow for a unique determination of the parameters residence time, surface diffusion coefficient, and net cross-section. Rather an estimation of parameter windows is possible by assuming meaningful values for the electron dissociation cross section. The model was applied to the experimental results for Cu(hfac)2 as a gas precursor. PMID- 22097533 TI - Superhydrophilic and tribological improvements of polymeric surfaces via plasma enhanced chemical vapor deposition ceramic coatings. AB - The main object of this study is the treatment of polymeric (PVC, PC) surfaces with the aim of inducing enhanced superhydrophilic characteristics together with nanohardness features; this would allow polymeric surfaces to have longer durability and prevent the accumulation of dirt on the surface which could disable the proper use of these polymeric surfaces. Indeed plastic surfaces are difficult substrates to be covered effectively and functionalized, mainly due to their high sensitivity to heat treatments and irradiation in the UV-Vis range together with their inert behavior. Their functionalization is achieved through the deposition of ceramic coatings such as titania (TiO2), on the polymeric surfaces via PECVD (Plasma Enhanced Chemical Vapor Deposition) at low temperatures. Characterizations are carried out by contact angle analysis for the superhydrophilic characteristics, and by nanoindentation analysis for the tribological features. A cold PECVD discontinuous method allowed us to improve nanohardness, reaching a value of 1.39 GPa which is nearly ten times higher than that of the uncoated polymeric substrate, and seems a promising solution for improving uniformity of the coatings. Superhydrophilic behavior of the activated TiO2 surfaces showed contact angle values lower than 10 degrees. PMID- 22097534 TI - Alumina coating on dense tungsten powder by fluidized bed metal organic chemical vapour deposition. AB - In order to study the feasibility of coating very dense powders by alumina using Fluidized Bed Metal Organic Chemical Vapour Deposition (FB-MOCVD), experiments were performed on a commercial tungsten powder, 75 microm in median volume diameter and 19,300 kg/m3 in grain density. The first part of the work was dedicated to the experimental study of the tungsten powder fluidization using argon as carrier gas at room temperature and at 400 degrees C. Due to the very high density of the tungsten powder, leading to low initial fixed bed heights and low bed expansions, different weights of powder were tested in order to reach satisfactory temperature profiles along the fluidized bed. Then, using argon as a fluidized bed former and aluminium acetylacetonate Al(C5O2H7)3 as a single source precursor, alumina thin films were deposited on tungsten particles at a low temperature range (e.g., 370-420 degrees C) by FB-MOCVD. The influence of the weight of powder, bed temperature and run duration was studied. Characterizations of the obtained samples were performed by various techniques including scanning electron microscopy (SEM) coupled with Energy Dispersive X-ray Spectroscopy (EDS) analyses, Field Emission Gun SEM (FEG-SEM) and Fourier Transform InfraRed (FT-IR) spectroscopy. The different analyses indicated that tungsten particles were uniformly coated by a continuous alumina thin film. The thickness of the film ranged between 25 and 80 nm, depending on the coating conditions. The alumina thin films were amorphous and contained carbon contamination. This latter may correspond to the adsorption of species resulting from incomplete decomposition of the precursor at so low deposition temperature. PMID- 22097535 TI - TiCp*(OMe)3 versus Ti(OMe)4 in atomic layer deposition of TiO2 with water--ab initio modelling of atomic layer deposition surface reactions. AB - It is a common finding that titanocene-derived precursors do not yield TiO2 films in ALD with water. For instance, ALD with Ti(OMe)4 and water gives 0.5 A/cycle, while TiCp*(OMe)3 does not show any growth (Me=CH3, Cp* = C5(CH3)5). This is apparently in contradiction with the computed reactivity of the ligands: the energetics of hydrolysis of the gas-phase precursor indicate that TiCp*(OMe)3 is more reactive to ligand elimination than Ti(OMe)4. However such a model of precursor reactivity neglects surface reactions such as adsorption, diffusion and desorption, all of which can have an important effect on ALD growth rate. A more accurate model of the surface reaction is needed to find the reason for the different behaviours of Ti(OMe)4 and TiCp*(OMe)3 in the ALD process. The more realistic surface model is a TiO2 slab that is periodic in three dimensions. These calculations reveal that TiCp*(OMe)3 does not chemisorb in the usual way because of extreme crowding of the Ti centre by Cp* and that this prevents ALD growth. PMID- 22097536 TI - Atomic vapor deposition approach to In2O3 thin films. AB - In2O3 thin films were grown by atomic vapor deposition (AVD) on Si(100) and glass substrates from a tris-guanidinate complex of indium [In(N(i)Pr2guanid)3] under an oxygen atmosphere. The effects of the growth temperature on the structure, morphology and composition of In2O3 films were investigated. X-ray diffraction (XRD) measurements revealed that In2O3 films deposited in the temperature range 450-700 degreesC crystallised in the cubic phase. The film morphology, studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM), was strongly dependent on the substrate temperature. Stoichiometric In2O3 films were formed under optimised processing conditions as was confirmed by X-ray photoelectron and X-ray excited Auger electron spectroscopies (XPS, XE-AES), as well as by Rutherford backscattering spectrometry (RBS). Finally, optical properties were investigated by photoluminescence (PL) measurements, spectroscopic ellipsometry (SE) and optical absorption. In2O3 films grown on glass exhibited excellent transparency (approximately 90%) in the Visible (Vis) spectral region. PMID- 22097537 TI - Controlling the crystallinity and roughness of atomic layer deposited titanium dioxide films. AB - The surface roughness of thin films is an important parameter related to the sticking behaviour of surfaces in the manufacturing of microelectomechanical systems (MEMS). In this work, TiO2 films made by atomic layer deposition (ALD) with the TiCl4-H2O process were characterized for their growth, roughness and crystallinity as function of deposition temperature (110-300 degrees C), film thickness (up to approximately 100 nm) and substrate (thermal SiO2, RCA-cleaned Si, Al2O3). TiO2 films got rougher with increasing film thickness and to some extent with increasing deposition temperature. The substrate drastically influenced the crystallization behaviour of the film: for films of about 20 nm thickness, on thermal SiO2 and RCA-cleaned Si, anatase TiO2 crystal diameter was about 40 nm, while on Al2O3 surface the diameter was about a micrometer. The roughness could be controlled from 0.2 nm up to several nanometers, which makes the TiO2 films candidates for adhesion engineering in MEMS. PMID- 22097538 TI - Atmospheric pressure chemical vapour deposition of 3C-SiC for silicon thin-film solar cells on various substrates. AB - The production of crystalline silicon thin-film solar cells on cost effective ceramic substrates depends on a highly reliable diffusion barrier to separate the light absorbing layers from the substrate. Ideally this intermediate layer should be deposited with cost effective techniques, be conductive and should feature optical confinement. Furthermore the intermediate layer should withstand high temperatures and harsh chemical environments like they occur during solar cell processing. Especially stability against oxidizing solvents like HNO3 or inactivity during e.g., oxide removing steps with HF is required. Crystalline silicon carbide (c-SiC) deposited by atmospheric pressure chemical vapour deposition (APCVD) can match all those requirements and additionally fits the thermal properties of crystalline silicon. The c-SiC intermediate layer is deposited from methyltrichlorosilane (MTS) and H2 at 1100 degrees C. Under these conditions, growth of solely cubic 3C-SiC could be observed by X-ray diffraction measurements. Use of such intermediate layers during high temperature steps prevents diffusion of transition metals, originating from the substrates, into active silicon layers. Doping of these 3C-SiC layers with nitrogen results in specific resistivity of less than 100 ohms cm. The different potentially cost effective substrates are made from graphite, crystalline silicon, sintered silicon carbide and sintered zircon (ZrSiO4). Surface properties of the coated substrates were investigated, explaining changes in surface roughness and influences on the solar cell processing. PMID- 22097539 TI - Electrical and optical performance of transparent conducting oxide films deposited by electrostatic spray assisted vapour deposition. AB - Transparent conducting oxide (TCO) films have the remarkable combination of high electrical conductivity and optical transparency. There is always a strong motivation to produce TCO films with good performance at low cost. Electrostatic Spray Assisted Vapor Deposition (ESAVD), as a variant of chemical vapour deposition (CVD), is a non-vacuum and low-cost deposition method. Several types of TCO films have been deposited using ESAVD process, including indium tin oxide (ITO), antimony-doped tin oxide (ATO), and fluorine doped tin oxide (FTO). This paper reports the electrical and optical properties of TCO films produced by ESAVD methods, as well as the effects of post treatment by plasma hydrogenation on these TCO films. The possible mechanisms involved during plasma hydrogenation of TCO films are also discussed. Reduction and etching effect during plasma hydrogenation are the most important factors which determine the optical and electrical performance of TCO films. PMID- 22097540 TI - Ultra-thin atomic layer deposited TiN films: non-linear I-V behaviour and the importance of surface passivation. AB - We report the electrical resistivity of atomic layer deposited TiN thin films in the thickness range 2.5-20 nm. The measurements were carried out using the circular transfer length method structures. For the films with thickness in the range of 10-20 nm, the measurements exhibited linear current-voltage (I-V) curves. The sheet resistance R(sh) was determined, and the resistivity was calculated. A value of 120 microohms-cm was obtained for a 20 nm TiN layer. With decreasing film thickness, the resistivity slightly increased and reached 135 microohms-cm for a 10 nm film. However, the measurements on 2.5-5.0 nm thick films revealed non-linear I-V characteristics, implying the dependence of the measured resistance, and therefore the resistivity, of the layers on applied voltage. The influence of the native oxidation due to the exposure of the films to air was taken into account. To fully eliminate this oxidation, a highly resistive amorphous silicon layer was deposited directly after the ALD of TiN. The electrical measurements on the passivated 2.5- and 3.5 nm TiN layers then exhibited linear I-V characteristics. A resistivity of 400 and 310 microohms-cm was obtained for a 2.5- and 3.5 nm TiN film, respectively. PMID- 22097541 TI - On the effects of electric fields in aerosol assisted chemical vapour deposition reactions of vanadyl acetylacetonate solutions in ethanol. AB - Thin films of thermochromic vanadium dioxide have been deposited on glass substrates at 530 degrees C from the aerosol assisted chemical vapour deposition of vanadyl acetylacetonate solutions in ethanol under the influence of electric fields. Electric fields were generated by applying a potential difference between the top plate and the substrate of the reactor. The deposited films were analysed and characterised using scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy and variable temperature UV/Visible spectroscopy. The application of an electric field led to significant changes in the deposited films microstructure and functional properties. It was found that an increase in electric field strength caused a decrease in crystallite size and in an increase in the change in transmission in the near infrared when compared to films grown without the use of an electric field. PMID- 22097542 TI - Linking the operating parameters of chemical vapor deposition reactors with film conformality and surface nano-morphology. AB - A multiscale modeling framework is used to couple the co-existing scales, i.e., macro-, micro- and nano-scale, in chemical vapor deposition (CVD) processes. The framework consists of a reactor scale model (RSM) for the description of the transport phenomena in the bulk phase (macro-scale) of a CVD reactor and two models for the micro- and nano-scale: (a) A feature scale model (FSM) describing the deposition of a film inside features on a predefined micro-topography on the wafer and (b) a nano-morphology model (NMM) describing the surface morphology evolution during thin film deposition on an initially flat surface. The FSM is deterministic and consists of three sub-models: A ballistic model for the species' transport inside features, a surface chemistry model, and a profile evolution algorithm based on the level set method. The NMM is stochastic and is based on the kinetic Monte Carlo method. The coupling of RSM with FSM is performed through a correction of the species consumption on the wafer. The linking of RSM with NMM is performed through "feeding" of the deposition rate calculated by RSM to the NMM. The case study is CVD of Silicon (Si) from Silane. The effect of the reactor's operating parameters on the Si film conformality inside trenches is investigated by the coupling of RSM with FSM. The formation of dimmers on an initially flat Si (001) surface as well as the periodic change of the surface nano-morphology is predicted. PMID- 22097543 TI - A study of pyrolysis of polymethylsiloxanes by Fourier transform infrared. AB - This paper is dedicated to a comparative study of pyrolysis of decamethylcyclopentasiloxane and hexamethyldisiloxane, widely used as precursors for CVD of silicon dioxide films. The pyrolysis process was carried out in a hot wall horizontal tube reactor made from quartz within the temperature range 25 1000 degrees C. FTIR spectroscopy has been used for the analysis of gaseous reaction products in the exhaust line of the reactor. It has been found that transformation of DMPSO was initiated by the open ring in the precursor molecules with its further transformation to linear biradicals followed by the chain's growth due to radical reactions. HMDSO transformation is connected with separation of silanon, silyl and methyl radicals with following multi-type interactions of siloxane radicals and formation of non-rigorously organized three dimensional molecules. PMID- 22097544 TI - Enhancement of crystallinity and optical properties of bilayer TiO2/ZnO thin films prepared by atomic layer deposition. AB - Bilayer and multilayer thin films are becoming increasingly important in the development of faster, smaller and more efficient electronic and optoelectronic devices. One of the motivations of applying bilayer or multilayer structures is to modify the optical properties of materials. Atomic layer deposition (ALD) is a variant of Chemical Vapour Deposition that can produce uniform and conformal thin films with well controlled nanostructures. In this study, we have demonstrated new findings of the use of ALD fabricated bilayer TiO2/ZnO thin films with enhanced crystallinity and optical properties. TiO2 films have been deposited at 300 degrees C for 1000 (51 nm in thickness) or 3000 (161 nm in thickness) deposition cycles onto glass and Si substrates. ZnO films are subsequently deposited on the TiO2 layers at 280 degrees C for 500 deposition cycles (55 nm). The crystallinity and optical properties of the TiO2/ZnO thin films have been analysed by X-ray diffraction, photoluminescence, UV-Vis spectroscopy, Atomic Force Microscopy and Scanning Electron Microscopy. XRD diffraction pattern confirmed the presence of ZnO with wutrtize crystal structure and TiO2 with anatase structure. It shows that the crystallinity of the TiO2 films has been improved with the deposition of ZnO. The intensity of UV luminescence has increased by almost 30% for TiO2/ZnO bilayer as compared to the single layer TiO2. The possible mechanism for the enhancement of the optical properties of bilayer TiO2/ZnO thin films will be discussed. PMID- 22097545 TI - SUBLIBOX: a proprietary solvent free method for intense vaporization of solid compounds. AB - Chemical vapour deposition and atomic layer deposition using precursors that are solids at ambient temperature and pressure present challenges due to the often low saturating vapour pressure of these compounds. Additional concerns arise from the difficulty to maintain a reproducible and stable precursor flow rate to the deposition chamber and from the possible particle contamination if suitable safeguards are not built into the precursor delivery line. In the present contribution, SUBLIBOX, a pilot industrial scale sublimator is presented. SUBLIBOX is based on a new sublimation process involving gas-solid fluidization technology. Aluminum acetyl-acetonate [Al(acac)3], a promising precursor for the processing of alumina films despite its low saturated vapour pressure, is used as a model, though technologically interesting system. Mass balance measurements, involving trapping of the sublimed precursor at the exit of the sublimation chamber, reveal that SUBLIBOX ensures (a) stable, (b) efficient, (c) reproducible and (d) long term precursor vapour flow rates. The process is particularly well adapted for delivering vapours to CVD reactors for coatings on glass and stainless steel or for producing optical fibbers preforms by various techniques. PMID- 22097546 TI - TiO2 coating of high surface area silica gel by chemical vapor deposition of TiCl4 in a fluidized-bed reactor. AB - TiO2 was deposited on high surface area porous silica gel (400 m2g(-1)) in a fluidized bed reactor. Chemical vapor deposition was employed for the coating under vacuum conditions with TiCl4 as precursor. Nitrogen physisorption, X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy and UV-vis spectroscopy were applied to characterize the obtained TiO2-SiO2 composites with different Ti loadings up to 5 wt%. Only a slight decrease in the specific surface area was detected at low Ti loadings. At a Ti loading of 2 wt%, TiO2 was found to be highly dispersed on the SiO2 surface likely in form of a thin film. At higher Ti loadings, two weak reflections corresponding to anatase TiO2 were observed in the diffraction patterns indicating the presence of crystalline bulk TiO2. High resolution XPS clearly distinguished two types of Ti species, i.e., Ti-O-Si at the interface and Ti-O-Ti in bulk TiO2. The presence of polymeric TiOx species at low Ti loadings was confirmed by a blue shift in the UV vis spectra as compared to bulk TiO2. All these results point to a strong interaction between the TiO2 deposit and the porous SiO2 substrate especially at low Ti loadings. PMID- 22097547 TI - Electric fields in the chemical vapour deposition growth of vanadium dioxide thin films. AB - Thin films of thermochromic vanadium dioxide have been the subject of intensive research in recent years year due to their postulated use as "intelligent" window coatings. The usefulness of such technology depends on a semi-conducting to metal transition with an associated change in infra-red optical properties. This exact nature of this transition depends on a large number of factors such as doping, crystallite size, strain, crystallographic orientation etc. In this paper we discuss the nature of these factors with a particular focus on how the application of electric fields in the deposition affects crystallite size and film strain with reference to recent results. PMID- 22097548 TI - Germanium nanowires with 3-nm-diameter prepared by low temperature vapour-liquid solid chemical vapour deposition. AB - We report the growth of germanium nanowires (Ge NWs) with single-step temperature method via vapour-liquid-solid (VLS) mechanism in the low pressure chemical vapour deposition (CVD) reactor at 300 degrees C, 280 degrees C, and 260 degrees C. The catalyst used in our experiment was Au nanoparticles with equivalent thicknesses of 0.1 nm (average diameter approximately 3 nm), 0.3 nm (average diameter approximately 4 nm), 1 nm (average diameter approximately 6 nm), and 3 nm (average diameter approximately 14 nm). The Gibbs-Thomson effect was used to explain our experimental results. The Ge NWs grown at 300 degrees C tend to have tapered structure while the Ge NWs grown at 280 degrees C and 260 degrees C tend to have straight structure. Tapering was caused by the uncatalysed deposition of Ge atoms via CVD mechanism on the sidewalls of nanowire and significantly minimised at lower temperature. We observed that the growth at lower temperature yielded Ge NWs with smaller diameter and also observed that the diameter and length of Ge NWs increases with the size of Au nanoparticles for all growth temperatures. For the same size of Au nanoparticles, Ge NWs tend to be longer with a decrease in temperature. The Ge NWs grown at 260 degrees C from 0.1-nm thick Au had diameter as small as approximately 3 nm, offering an opportunity to fabricate high-performance p-type ballistic Ge NW transistor, to realise nanowire solar cell with higher efficiency, and also to observe the quantum confinement effect. PMID- 22097549 TI - Investigation of thermal and hot-wire chemical vapor deposition copper thin films on TiN substrates using CupraSelect as precursor. AB - Copper films were deposited on oxidized Si substrates covered with TiN using a novel chemical vapor deposition reactor in which reactions were assisted by a heated tungsten filament (hot-wire CVD, HWCVD). Liquid at room temperature hexafluoroacetylacetonate Cu(I) trimethylvinylsilane (CupraSelect) was directly injected into the reactor with the aid of a direct-liquid injection (DLI) system using N2 as carrier gas. The deposition rates of HWCVD Cu films obtained on TiN covered substrates were found to increase with filament temperature (65 and 170 degrees C were tested). The resistivities of HWCVD Cu films were found to be higher than for thermally grown films due to the possible presence of impurities into the Cu films from the incomplete dissociation of the precursor and W impurities caused by the presence of the filament. For HWCVD films grown at a filament temperature of 170 degrees C, smaller grains are formed than at 65 degrees C as shown from the taken SEM micrographs. XRD diffractograms taken on Cu films deposited on TiN could not reveal the presence of W compounds originating from the filament because the relative peak was masked by the TiN [112] peak. PMID- 22097550 TI - Advanced APCVD-processes for high-temperature grown crystalline silicon thin film solar cells. AB - Crystalline silicon thin film (cSiTF) solar cells based on the epitaxial wafer equivalent (EpiWE) concept combine advantages of wafer-based and thin film silicon solar cells. In this paper two processes beyond the standard process sequence for cSiTF cell fabrication are described. The first provides an alternative to wet chemical saw damage removal by chemical vapor etching (CVE) with hydrogen chloride in-situ prior to epitaxial deposition. This application decreases the number of process and handling steps. Solar cells fabricated with different etching processes achieved efficiencies up to 14.7%. 1300 degrees C etching temperature led to better cell results than 1200 degrees C. The second investigated process aims for an improvement of cell efficiency by implementation of a reflecting interlayer between substrate and active solar cell. Some characteristics of epitaxial lateral overgrowth (ELO) of a patterned silicon dioxide film in a lab-type reactor constructed at Fraunhofer ISE are described and first solar cell results are presented. PMID- 22097551 TI - Integration of metal organic chemical vapour deposition and wet chemical techniques to obtain highly ordered porous ZnO nanoplatforms. AB - Large-area, highly ordered ZnO micropores-arrays consisting of ZnO nanotubes delimited by ZnO nanorods have been successfully fabricated and tested for protein sensing applications. ZnO seed layers have been deposited by Metal Organic Chemical Vapour Deposition and readily patterned by Colloidal Lithography to attain ZnO nanorods growth at selective sites by Chemical Bath Deposition. The used synthetic approach has been proven effective for the easy assembly of ZnO nanoplatforms into high-density arrays. Both patterned and unpatterned ZnO nanorods have been morphologically and compositionally characterised and, thus, tested for model studies of protein mobility at the interface. The patterned layers, having a higher contribution of surface polar moieties than the corresponding unpatterned surfaces, exhibit a reduced lateral diffusion of the adsorbed protein. This evidence is related to the intrinsic porous nature of the ZnO hemispherical arrays characterised by a nanotube-nanorod hybrid networks. The present study gives a great impetus to the fabrication of tunable ZnO nanoplatforms having multiple morphologies and exceptionally high surface areas suitable for application in sensing devices. PMID- 22097552 TI - Diamond layers grown by chemical vapor deposition on NbN systems and NbN/SiO2 based devices. AB - Deposits of individual diamond grains and continuous polycrystalline diamond layers have been generated by means of a HFCVD technique onto different types of untreated or seeded NbN surfaces. To test the feasibility of using diamond layers as protective coatings for aerospace applications, we carried out diamond deposition onto the lithographically defined NbN microelectrodes of a NbN/SiO2 multifinger device. The morphological and structural features of the diamond deposits and of the substrates were characterized by FE-SEM, XRD and Raman spectroscopy. The preferential growth of diamond on the superconductive NbN enables the selective coating of the NbN microstripes sputtered on the insulating SiO2. Moreover the diamond coating procedure is able to preserve the structural integrity of the substrate material and to retain the shaped architecture of the device. For the polycrystalline diamond layers grown on NbN a residual stress of 9.8 GPa, largely due to thermal stress, has been estimated by Raman analysis. The diamond coatings of the NbN-based architectures result to be mechanically stable. PMID- 22097553 TI - Relevance of thermodynamic and kinetic parameters of chemical vapor deposition precursors. AB - We have studied various metallorganic and organometallic compounds by simultaneous nonisothermal thermogravimetric and differential thermogravimetric analyses to confirm their volatility and thermal stability. The equilibrium vapor pressures of the metallorganic and organometallic compounds were determined by horizontal dual arm single furnace thermoanalyzer as transpiration apparatus. Antoine coefficients were calculated from the temperature dependence equilibrium vapor pressure data. The model-fitting solid-state kinetic analyses of Al(acac)3, (acac = acetylacetonato), Cr(CO)6, Fe(Cp)2, (Cp-cyclopentadienyl), Ga(acac)3, Mn(tmhd)3, and Y(tmhd)3 (tmhd = 2,2,6,6,-tetramethyl-3,5-heptanedionato) revealed that the processes follow diffusion controlled, contracting area and zero order model sublimation or evaporation kinetics. The activation energy for the sublimation/evaporation processes were calculated by model-free kinetic methods. Thin films of nickel and lanthanum-strontium-manganite (LSM) are grown on silicon substrate at 573 K using selected metallorganic complexes of Ni[(acac)2en], La(tmhd)3, Sr(tmhd)2 and Mn(tmhd)3 as precursors by plasma assisted liquid injection chemical vapor deposition (PA-LICVD). The deposited films were characterized by scanning electron microscopy and energy dispersive X-ray analysis for their composition and morphology. PMID- 22097554 TI - Decomposition schemes of copper(I) N,N'-diisopropylacetamidinate during chemical vapor deposition of copper. AB - Copper(I) N,N'-diisopropylacetamidinate [Cu(amd)]2 (amd = CH(CH3)2NC(CH3)NCH(CH3)2), an oxygen and halogen-free compound, was previously tested as precursor for pure copper CVD and ALD films. The present work deals with the investigation of the composition and of the reactivity of the gas phase during the CVD process. The work was performed by mass spectrometry as a function of temperature in two different, though complementary environments: (A) in a miniature, low pressure hot wall CVD reactor, (B) in a cold wall reactor operating at subatmospheric pressure. (A) revealed that the onset of thermal decomposition is 140 degrees C and 130 degrees C in vacuum and in the presence of hydrogen, respectively; maximal decomposition degree is reached at temperature higher than 200 degrees C. The protonated ligand H(amd) is the main gaseous decomposition by-product; propene CH2=CHCH3, acetonitryle CH3C[triple bond]N and iminopropane CH3C(CH3)=NH are also observed in vacuum. Heterogeneous decomposition mechanism both in vacuum and hydrogen presence is discussed. PMID- 22097555 TI - Low temperature silicon nitride by hot wire chemical vapour deposition for the use in impermeable thin film encapsulation on flexible substrates. AB - High quality non porous silicon nitride layers were deposited by hot wire chemical vapour deposition at substrate temperatures lower than 110 degrees C. The layer properties were investigated using FTIR, reflection/transmission measurements and 1:6 buffered HF etching rate. A Si-H peak position of 2180 cm( 1) in the Fourier transform infrared absorption spectrum indicates a N/Si ratio around 1.2. Together with a refractive index of 1.97 at a wavelength of 632 nm and an extinction coefficient of 0.002 at 400 nm, this suggests that a transparent high density silicon nitride material has been made below 110 degrees C, which is compatible with polymer films and is expected to have a high impermeability. To confirm the compatibility with polymer films a silicon nitride layer was deposited on poly(glycidyl methacrylate) made by initiated chemical vapour deposition, resulting in a highly transparent double layer. PMID- 22097556 TI - Plasma processing of nanomaterials: emerging technologies for sensing and energy applications. AB - Plasma processing represents an attractive and versatile option for the fabrication of low-dimensional nanomaterials, whose chemical and physical properties can be conveniently tailored for the development of advanced technologies. In particular, Plasma Enhanced-Chemical Vapor Deposition (PE-CVD) is an appealing route to multi-functional oxide nanoarchitectures under relatively mild conditions, owing to the unique features and activation mechanisms of non-equilibrium plasmas. In this context, the potential of plasma assisted fabrication in advanced nanosystem development is discussed. After a brief introduction on the basic categories of plasma approaches, the perspectives of application to CVD processes are commented, reporting on the growth and characterization of Co3O4 nanomaterials as a case study. Besides examining the interrelations between the material properties and the synthesis conditions, special focus is given to their emerging applications as catalysts for photo assisted hydrogen production and solid state gas sensors. PMID- 22097557 TI - Aerosol assisted chemical vapour deposition control parameters for selective deposition of tungsten oxide nanostructures. AB - Tungsten oxide films were deposited via Aerosol Assisted Chemical Vapour Deposition (AACVD) from the single-source precursor W(OPh)6. Film morphology and optimum deposition temperatures for formation of quasi-one-dimensional structures is influenced by the solvent 'carrier' used for deposition of the films with bulk porous films and nanostructured needles, hollow tubes and fibres obtained dependent on the solvent used and the deposition temperature. This influence of solvent could be exploited for the synthesis of other nanomaterials, and so provide a new and versatile route to develop and integrate nanostructured materials for device applications. PMID- 22097558 TI - BiFeO3 films doped in the A or B sites: effects on the structural and morphological properties. AB - Metal-Organic Chemical Vapor Deposition (MOCVD) has been applied to the fabrication of BiFeO3 films undoped and doped with Ba or Ti on SrTiO3 (100) and YSZ (100) substrates. The films have been deposited using a multi-metal source, consisting of the Bi(phenyl)3, Fe(tmhd)3 and Ba(hfa)2 tetraglyme or Ti(tmhd)2(O iPr)2 (phenyl = -C6H5, H-tmhd = 2,2,6,6-tetramethyl-3,5-heptandione; O-iPr = iso propoxide; H-hfa = 1,1,1,5,5,5-hexafluoro-2,4-pentanedione; tetraglyme = CH3O(CH2CH2O)4CH3) precursor mixture. The structural and morphological characterization of films has been carried out using X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). Chemical compositional studies have been performed by energy dispersive X-ray (EDX) analysis. Structural and morphological characterizations point to the formation of homogeneous and flat surfaces for both undoped and doped BiFeO3 films. PMID- 22097559 TI - In situ gas phase measurements during metal alkylamide atomic layer deposition. AB - Metal alkylamide compounds, such as tetrakis(ethylmethylamido) hafnium (TEMAH), represent a technologically important class of metalorganic precursors for the deposition of metal oxides and metal nitrides via atomic layer deposition (ALD) or chemical vapor deposition. The development of in situ diagnostics for processes involving these compounds could be beneficial in, e.g., developing deposition recipes and validating equipment-scale simulations. This report describes the performance of the combination of two techniques for the simultaneous, rapid measurement of the three major gas phase species during hafnium oxide thermal ALD using TEMAH and water: TEMAH, water, and methylethyl amine (MEA), the only major reaction by-product. For measurement of TEMAH and MEA, direct absorption methods based on a broadband infrared source with different mid-IR bandpass filters and utilizing amplitude modulation and synchronous detection were developed. For the measurement of water, wavelength modulation spectroscopy utilizing a near-IR distributed feedback diode laser was used. Despite the relatively simple reactor geometry employed here (a flow tube), differences were easily observed in the time-dependent species distributions in 300 mL/min of a helium carrier gas and in 1000 mL/min of a nitrogen carrier gas. The degree of TEMAH entrainment was lower in 300 mL/min of helium compared to that in 1000 mL/min of nitrogen. The capability to obtain detailed time-dependent species concentrations during ALD could potentially allow for the selection of carrier gas composition and flow rates that would minimize parasitic wall reactions. However, when nitrogen was employed at the higher flow rates, various flow effects were observed that, if detrimental to a deposition process, would effectively limit the upper range of useful flow rates. PMID- 22097560 TI - Investigation of substrate influence on tin dioxide nanostructures synthesized using horizontal furnace. AB - SnO2 nanostructures were directly synthesised by chemical vapour transport on different substrates in a horizontal furnace. The influence of substrate on the morphology of these nanostructures was investigated by changing the substrate type, coating, and temperature. The SnO2 nanowires and nanorods were one dimensional (1D) structures with widths and lengths of 50-200 nm and several micrometers respectively. Scanning electron microscope (SEM) images show formation of short nanorods with lengths of less than 1 microm on indium-tin oxide (ITO) substrates. The effect of substrate temperature on growth was studied. SnO2 nanowires were obtained using silicon substrate, and the effect of Au coating on the size and morphology of these structures was proposed. By coating the Si wafer with a thin layer of Au, the size of the nanostructure was reduced and the length increased. The differences in size and morphology are shown by transmission electron microscopy (TEM). X-ray diffraction (XRD) spectra show tetragonal structures for both substrates. PMID- 22097561 TI - Deposition of thermal and hot-wire chemical vapor deposition copper thin films on patterned substrates. AB - In this work we study the hot-wire chemical vapor deposition (HWCVD) of copper films on blanket and patterned substrates at high filament temperatures. A vertical chemical vapor deposition reactor was used in which the chemical reactions were assisted by a tungsten filament heated at 650 degrees C. Hexafluoroacetylacetonate Cu(I) trimethylvinylsilane (CupraSelect) vapors were used, directly injected into the reactor with the aid of a liquid injection system using N2 as carrier gas. Copper thin films grown also by thermal and hot wire CVD. The substrates used were oxidized silicon wafers on which trenches with dimensions of the order of 500 nm were formed and subsequently covered with LPCVD W. HWCVD copper thin films grown at filament temperature of 650 degrees C showed higher growth rates compared to the thermally ones. They also exhibited higher resistivities than thermal and HWCVD films grown at lower filament temperatures. Thermally grown Cu films have very uniform deposition leading to full coverage of the patterned substrates while the HWCVD films exhibited a tendency to vertical growth, thereby creating gaps and incomplete step coverage. PMID- 22097562 TI - N-type crystalline silicon films free of amorphous silicon deposited on glass by HCl addition using hot wire chemical vapour deposition. AB - Since n-type crystalline silicon films have the electric property much better than those of hydrogenated amorphous and microcrystalline silicon films, they can enhance the performance of advanced electronic devices such as solar cells and thin film transistors (TFTs). Since the formation of amorphous silicon is unavoidable in the low temperature deposition of microcrystalline silicon on a glass substrate at temperatures less than 550 degrees C in the plasma-enhanced chemical vapour deposition and hot wire chemical vapour deposition (HWCVD), crystalline silicon films have not been deposited directly on a glass substrate but fabricated by the post treatment of amorphous silicon films. In this work, by adding the HCl gas, amorphous silicon-free n-type crystalline silicon films could be deposited directly on a glass substrate by HWCVD. The resistivity of the n type crystalline silicon film for the flow rate ratio of [HCl]/[SiH4] = 7.5 and [PH3]/[SiH4] = 0.042 was 5.31 x 10(-4) ohms cm, which is comparable to the resistivity 1.23 x 10(-3) ohms cm of films prepared by thermal annealing of amorphous silicon films. The absence of amorphous silicon in the film could be confirmed by high resolution transmission electron microscopy. PMID- 22097563 TI - Understanding 'clean-up' of III-V native oxides during atomic layer deposition using bulk first principles models. AB - The use of III-V materials as the channel in future transistor devices is dependent on removing the deleterious native oxides from their surface before deposition of a gate dielectric. Trimethylaluminium has been found to achieve in situ 'clean-up' of the oxides of GaAs and InGaAs before atomic layer deposition (ALD) of alumina. Here we propose six reaction mechanisms for 'clean-up,' featuring exchange of ligands between surface atoms, reduction of arsenic oxide by methyl groups and desorption of various products. We use first principles Density Functional Theory (DFT) to determine which mechanistic path is thermodynamically favoured based on models of the bulk oxides and gas-phase products. We therefore predict that 'clean-up' of arsenic oxides mostly produces As4 gas. Most C is predicted to form C2H6 but with some C2H4, CH4 and H2O. An alternative pathway is non-redox ligand exchange, which allows non-reducible oxides to be cleaned-up. PMID- 22097564 TI - Optimization of chemical vapor deposition diamond films growth on steel: correlation between mechanical properties, structure, and composition. AB - In the present work we perform optimization of mechanical and crystalline properties of CVD microcrystalline diamond films grown on steel substrates. A chromium-nitride (Cr-N) interlayer had been previously proposed to serve as a buffer for carbon and iron inter-diffusion and as a matching layer for the widely differing expansion coefficients of diamond and steel. However, adhesion and wear as well as crystalline perfection of diamond films are strongly affected by conditions of both Cr-N interlayer preparation and CVD diamond deposition. In this work we assess the effects of two parameters. The first one is the temperature of the Cr-N interlayer preparation: temperatures in the range of 500 degrees C-800 degrees C were used. The second one is diamond film thickness in the 0.5 microm-2 microm range monitored through variation of the deposition time from approximately 30 min to 2 hours. The mechanical properties of so deposited diamond films were investigated. For this purpose, scratch tests were performed at different indentation loads. The friction coefficient and wear loss were assessed. The mechanical and tribological properties were related to structure, composition, and crystalline perfection of diamond films which were extensively analyzed using different microscopic and spectroscopic techniques. It was found that relatively thick diamond film deposited on the Cr-N interlayer prepared at the temperature similar to that of the CVD process has the best mechanical and adhesion strength. This film was stable without visible cracks around the wear track during all scratch tests with different indentation loads. In other cases, cracking and delamination of the films took place at low to moderate indentation loads. PMID- 22097565 TI - Chemical vapor deposition of Ni-C films from bis-(ethylcyclopentadienyl) nickel. AB - Metal-organic chemical vapor deposition (MOCVD) is widely used for deposition of various nickel-containing coatings, such as catalytic nickel thin films and nanoparticles, nickel silicide alloys and magnetic carbon-nickel nanocomposite layers. Here we report preliminary results from an attempt to use bis (ethylcyclopentadienyl) nickel [(EtCp)2Ni] as a precursor for MOCVD of Ni-C thin films in the (EtCp)2Ni-Ar and (EtCp)2Ni-H2-Ar reaction systems. Mechanism of precursor fragmentation was proposed on the basis of the results from a study of gaseous reaction products in the exhaust line of the reactor by means of mass spectrometry. It was found that an introduction of hydrogen in the gas phase led to an increase in conversion rate of the precursor. Deposited films were analyzed by means of atomic force microscope (AFM), scanning electron microscopy (SEM), X ray fluorescence spectroscopy (XFS). The effect of hydrogen on growth rate, composition, and morphology of the deposited Ni-C films were experimentally studied. PMID- 22097566 TI - Texture and surface morphology effects on tetragonal phase stabilization in ZrO2 films deposited by metal-organic chemical vapor deposition. AB - Tetragonal zirconia coatings (ZrO2) without doping any trivalent impurities have been deposited by metal-organic chemical vapor deposition (MOCVD) on (100) Si single crystals, using Zr(thd)4 precursor. The surface and cross-section morphologies were observed with Field-Emission-Gun Scanning Electron Microscopy (FEG-SEM). The crystalline structures were characterized by grazing incident X ray diffraction (GIXRD). Crystallographic textures of these films were studied for both {011}t and {110}t planes by pole figure recording by X-ray diffraction under a 4-circle goniometer. The internal stresses were measured with the use of sin2 psi method. In order to study the relationship of microstructures and tetragonal phase stabilization in ZrO2 films, annealing experiments were taken at different temperature. The results show that the critical crystallite size for tetragonal to monoclinic phase transformation is different for samples with different initial microstructures. Besides the critical crystallite size and the residual stress, the texture and crystallite morphology of the ZrO2 films are responsible for the stabilization of the metastable tetragonal phase. PMID- 22097567 TI - Dia-magnetic to ferro-magnetic behavioral change of Fe-catalysts based nitrogenated carbon nanotubes (NCNTs) by the process of chlorination/oxidation. AB - In this work, we have synthesized multiwall nitrogenated carbon nanotubes (MW NCNTs) with Fe-catalysts by the microwave plasma-enhanced chemical vapor deposition process @950 degrees C and subsequently functionalized with chlorine and oxygen. The dia-magnetic behavioral M-H loop of non-functionalized MW-NCNTs were turn into ferromagnetic behaviors by the process of chlorination and oxidation respectively; which were characterized by means of superconducting quantum interference device magnetometer within the temperature range 5-300 K. A prominent cusp like behavior is also observed at around approximately 45 K in M(FC) and M(ZFC) measurements confirming the ferromagnetic behaviors of these MW NCNTs after chlorination and oxidation. PMID- 22097568 TI - Chemical vapour deposition of nitrogen-doped titanium dioxide thin films. AB - Nitrogen-doped titanium dioxide is often considered as a promising nanomaterial for photocatalytic applications. Here we report the first results of a study of APCVD of N-doped TiO2 thin films prepared with the use of ammonia as a source of nitrogen and titanium tetraisopropoxide (TTIP) as a source of Ti and O atoms. The obtained films were analyzed with X-ray diffraction, infrared spectroscopy, atomic force microscopy, X-ray photoelectron spectroscopy, UV-Vis spectroscopy, and ellipsometry. It was found that the film growth rate in the TTIP-NH3-Ar reaction system varied insignificantly with substrate temperature in the range of 450,..., 750 degrees C and did not exceed 4.4 nm/min. Yellow and orange layers with nitrogen content of about 7.6% were formed at the deposition temperature higher than 600 degrees C. The results of the structure analysis of the deposited films showed that addition of ammonia led to stabilization of the amorphous phase in the films. The effect of ammonia on optical and photocatalytic properties was also considered. PMID- 22097569 TI - Fabrication of CuxGey nanoplatelets. AB - Modern technologies demand novel alloy materials for advanced devices and applications. Here we report on Low Pressure Chemical Vapor Deposition (LPCVD) of Ge2Me6 and SnMe4 leading to deposition of nanoplatelets along with nanoparticles. According to analytical techniques (Raman spectroscopy, ED, EDX, SEM and HRTEM) the nanoplatelets up to several tens of microm in length have been prepared in two alloy modifications orthorhombic Cu3Ge and hexagonal Cu86Ge14. Thickness of the nanoplatelets ranges from 50 to 150 nm. CuSn seeds served for the growth of Ge nanoparticles scattered among nanoplatelets. PMID- 22097570 TI - One dimensional aluminum nitride nanostructures: synthesis, structural, and luminescence properties. AB - Aluminum nitride (AIN) is a direct bandgap semiconductor with a bandgap about 6.1 eV at room temperature, the largest among semiconductors. This paper emphasizes experimental results of the growth and optical properties of AIN nanostructures by direct nitridation. The nitridation process was performed by chemical vapor deposition method with nitrogen (N2) gas flow. AIN nanostructures were analyzed by scanning electron microscope (SEM) equipped with energy-dispersive X-ray (EDX) spectroscope and photoluminescence (PL) spectroscopy. AIN nanowires with different widths from ultrathin to thick were synthesized with this method. All of the samples had high purity without presence of any other material in EDX spectrum. The PL spectra were obtained by a 325-nm helium-cadmium (He-Cd) laser as the excitation source showing high-intensity light emitting visible wavelengths for these structures at room temperature. PMID- 22097571 TI - Growth of chromium carbide in a hot wall DLICVD reactor. AB - Chromium carbide coatings were grown at 748 K in a hot wall CVD reactor fed by sublimation of bis(benzene)chromium, BBC (MOCVD) and by direct liquid injection using a BBC/toluene solution (DLICVD). The two types of coatings exhibit an amorphous structure and the same C content (22 at.%). DLICVD permits delivering higher mass flow rate of precursors and consequently the growth rate is 3 times higher and the thickness uniformity is better than using MOCVD. Chromium metal deposition has also been investigated by DLICVD in this hot wall reactor using BBC/toluene/additive as precursor. The purpose of the additive is to block carbide formation. Two additives have been studied: (i) hexachlorobenzene (C6Cl6) and (ii) thiophenol (C6H5SH). The ratio additive/BBC required for Cr metal deposition is a few percent. In this process, C6Cl6 is not decomposed and only traces of Cl (0.4 at.%) are found in the coatings. For a ratio C6Cl6/BBC > 27% the growth of any coating is blocked. The gas phase containing C6H5SH is more reactive since the onset of deposition occurs approximately 50 K before the temperature of the chlorinated compound. Furthermore, a sulfur contamination of 3 at.% has been analyzed in the coatings revealing a partial decomposition of the additive. The results are detailed and discussed in relation with previous works. PMID- 22097572 TI - Metal organic chemical vapour deposition of vertically aligned ZnO nanowires using oxygen donor adducts. AB - Vertically aligned zinc oxide (ZnO) nanowires (NWs) have been grown by liquid injection Metal Organic Chemical Vapour Deposition, using oxygen donor adducts of Me2Zn. The growth and characterisation of the nanowires grown using [Me2Zn(L)] where L = monodentate ethers, tetrahydrofuran (C4H8O) (1), tetrahydropyran (C5H10O) (2), furan (C4H4O) (3) and the bidentate ethers, 1,2-dimethoxyethane (C4H12O2,) (4) 1,4-dioxane (C4H8O2) (5) and 1,4-thioxane (C4H8SO) (6) is discussed. Single crystal X-ray structures of (4), (5), (6) have been established and are included here. The ZnO NWs were deposited in the absence of a seed catalyst on Si(111) and F-doped SnO2/glass substrates over the temperature range 350-600 degrees C. X-ray diffraction (XRD) data shows that the nanowires grown from all adduct precursors were deposited in the wurtzitic phase. PMID- 22097573 TI - On the reliability of heteronuclear precursors-ligand effects in the Li-MOCVD synthesis of SrTiO3 films. AB - Strontium titanate SrTiO3 thin films are highly perspective as gate dielectric material. Difference in volatility of the common homometallic precursors strontium beta-diketonates and titanium alkoxides remains major hinder for preparation of high quality coatings based on this phase. An attractive alternative in its synthesis by MOCVD is provided by application of heterometallic mixed-ligand complexes, Sr2Ti2(beta-diket)4(OR)8(ROH)x. Mass spectrometric study reveals, however, that none of these species can be considered a true single-source precursor. The relative stability of the molecules in solution and the congruence of in-situ release of homometallic species on evaporation are, on the other hand, crucial for the quality of the produced films and are strongly influenced by the nature of alkoxide ligands, OR. The historically first discovered representative of this heterometallic family, a sec-alkoxide derivative Sr2Ti2(thd)4(O(i)Pr)8, is in fact unexpectedly unstable, transforming in solution into Sr2Ti(thd)4(O(i)Pr)4((i)PrOH), which explains difficulties in keeping the correct stoichiometry using isopropoxide precursor. The primary alkoxide complexes, Sr2Ti2(thd)4(OR)8(ROH)2, R = Et, (n)Pr are also unstable yielding Sr4Ti2(thd)4(OR)8(ROH)2 on decomposition. The best solution stability and most uniform evaporation was observed for the iso-derivative, Sr2Ti2(thd)4(O(i)Bu)8, permitting to apply it in long term experiments under industrial process conditions. Present contribution provides detailed experimental comparison between and sec-and iso-alkoxide derivatives and sheds light on the influence of the ligand on molecular stability of a precursor and how it influences the quality of the derived oxide film, especially in relation to its electrophysical properties. PMID- 22097574 TI - Effects of interfacial layer on characteristics of TiN/ZrO2 structures. AB - To minimize the formation of unwanted interfacial layers, thin interfacial layer (ZrCN layer) was deposited between TiN bottom electrode and ZrO2 dielectric in TiN/ZrO2/TiN capacitor. Carbon and nitrogen were also involved in the layer because ZrCN layer was thermally deposited using TEMAZ without any reactant. Electrical characteristics of TiN/ZrO2/TiN capacitor were improved by insertion of ZrCN layer. The oxidation of TiN bottom electrode was largely inhibited at TiN/ZrCN/ZrO2 structure compared to TiN/ZrO2 structure. While the sheet resistance of TiN/ZrCN/ZrO2 structure was constantly sustained with increasing ZrO2 thickness, the large increase of sheet resistance was observed in TiN/ZrO2 structure after 6 nm ZrO2 deposition. When ZrO2 films were deposited on ZrCN layer, the deposition rate of ZrO2 also increased. It is believed that ZrCN layer acted both as a protection layer of TiN oxidation and a seed layer of ZrO2 growth. PMID- 22097575 TI - An aerosol-process for the synthesis of nanostructured molybdenum oxide catalysts by integrated chemical vapour synthesis/chemical vapour deposition at atmospheric pressure. AB - We report the synthesis of composite nanoparticles by an integrated CVS/CVD process at atmospheric pressure. Iron oxide and silica support particles were generated by chemical vapour synthesis (CVS), using Fe(CO)5 and Si(OC2H5)4 and were directly coated in the aerosol state with molybdenum oxide by chemical vapour deposition of Mo(CO)6. Depending on the CVS temperature hematite (600 degrees C) or maghemite (1500 degrees C) iron oxide phases were determined by XRD and FTIR. Core-shell structures with a coating thickness in the lower nm range were obtained for CVD temperatures below 150 degrees C. Complete encapsulation of the core particles and uniform elemental distribution is shown by TEM and EELS measurements. Higher CVD temperatures lead to unwanted homogenous decomposition of the molybdenum precursor. Additional aerosol temperature treatment was used to reach further oxidation and the formation of a mixed oxide shell, indicated by FTIR measurements. The results show the potential of the process for the synthesis of structured core-shell nanoparticles. PMID- 22097576 TI - Stability of high temperature chemical vapor deposited silicon based structures on metals for solar conversion. AB - Highly crystallized silicon layers were grown on metal sheets at high temperature (950 degrees C) by thermal CVD from silane. An intermediate buffer layer was mandatory to prevent interdiffusion and silicide formation but also to compensate lattice parameters and thermal expansion coefficients mismatches between metal and silicon and ideally transfer some crystalline properties (grain size, texture) from the substrate to the silicon layer. After a thermodynamic study, aluminum nitride or titanium nitride diffusion barrier layers were selected and processed by CVD. The structure and the interfaces stabilities of these silicon/nitride/metal stacks were studied by field effect gun scanning and transmission electron microscopy, X-ray diffraction, Raman and energy dispersive X-ray spectroscopy. As a result, TiN deposited by CVD appears to be an efficient material as a buffer layer between steel and silicon. PMID- 22097577 TI - Methyldichloroborane evidenced as an intermediate in the chemical vapour deposition synthesis of boron carbide. AB - The most recent ceramic-matrix composites (CMC) considered for long-life applications as thermostructural parts in aerospace propulsion contain, among others, boron-rich phases like boron carbide. This compound is prepared by thermal Chemical Vapour Infiltration (CVI), starting from precursors like boron halides and hydrocarbons. We present a study aiming at a precise knowledge of the gas-phase composition in a hot-zone LPCVD reactor fed with BCl3, CH4 and H2, which combines experimental and theoretical approaches. This work has brought strong evidences of the presence of Methydichloroborane (MDB, BCl2CH3) in the process. It is demonstrated that this intermediate, the presence of which had never been formally proved before, appears for processing temperatures slightly lower than the deposition temperature of boron carbide. The study features quantum chemical computations, which provide several pieces of information like thermochemical and kinetic data, as well as vibration and rotation frequencies, reaction kinetics computations, and experimental gas-phase characterization of several species by FTIR, for several processing parameter sets. The main results are presented, and the place of MDB in the reaction scheme is discussed. PMID- 22097578 TI - Microstructure characteristics of ZrO2 coating produced by atmospheric pressure chemical vapor deposition. AB - To settle the problem of low growth rate when prepare ZrO2 thermal barrier coating by Metalorganic CVD (MOCVD), a simple method was employed-atmospheric pressure CVD (APCVD). The paper firstly thermodynamic calculated the effect of O/Zr ratio and temperature on phase formation at various H/C ratios for ZrCl4-CO2 H2-Ar system. With temperature increment, the solid phase changes from C+ monoclinic ZrO2 to Monoclinic ZrO2 then to tetragonal ZrO2. With the increase of H/C ratio, the phase zone of C+ monoclinic ZrO2 expands. XRD and Raman spectrum were employed to measure phase structure of ZrO2 coating at different temperature. At 1300 degrees C, the coating contains a small amount tetragonal ZrO2 phase besides monoclinic phase; at 1100 degrees C, the coating is composed of monoclinic ZrO2 phase and a little C. The surface SEM images show the small grains evolve to polycrystals which have clear crystal form when raising temperature. The cross-section images show that dense ZrO2 column crystals arrange normal to the substrate. PMID- 22097579 TI - Transient stages in the chemical vapor deposition of silicon carbide. AB - Transient CVD experiments were simulated by varying continuously the deposition temperature or the initial gas flow rates (Q(MTS) or Q(H2)). Their consequences on the physicochemical properties of the coatings have been first examined. The adhesion of SiC/SiC bilayers containing these "transient interphases" (phi(Tr)) was investigated by scratch testing. For transient stages resulting from a decrease of Q(MTS) or T, free silicon can be co-deposited in proportions depending on alpha = Q(H2)/Q(MTS), T and P. This phenomenon is related to the high reactivity of the Si bearing species and is activated by high T and P and low a values. In this case, the continuous covalent bonding through the Si-rich interphases preserves the adhesion between the two SiC layers. Transient stages resulting from a decrease of Q(H2) lead first to larger and columnar SiC grains and finally to the deposition of anisotropic carbon, due to the formation of unsaturated hydrocarbons in the gas phase. The interphases with the highest carbon concentrations and thicknesses lead to delamination and local chipping of the outer SiC layer. The poor shear strength of these continuous and anisotropic layers is detrimental to the adherence of the bilayers. PMID- 22097580 TI - Durability of silver nanoparticulate films within a silica matrix by flame assisted chemical vapour deposition for biocidal applications. AB - Healthcare acquired infection (HCAI) rates have come under increasing scrutiny in recent years and been a major priority for health professionals in the UK and elsewhere. Of particular concern is the rise of so called 'superbugs', or those resistant to conventional antibiotics, such as Escherichia coli, Clostridium difficile and methicillin resistant Staphylococcus aureus (MRSA). The reasons for this rise are many and complex, but one important factor is bacterial survival rates on wards and other hospital areas. In this respect, nanostructured biocidal surfaces offer a potentially powerful weapon in the fight against HCAI. In addition to providing a toxic environment to a range of infectious disease causing bacteria (while remaining harmless to human health), any potential bioactive coated surface is required to be durable enough to withstand regular hospital cleaning methods without a reduction in biocidal activity over time and be economically viable to mass produce. The flame assisted chemical vapour deposition (FACVD) of silver and silver/silica films offer a means of producing such surfaces. In this work, we report investigations into a wide range of experimental factors and parameters affecting film durability, including burner head design and relative water vapour content in the flame environment. The produced films were assessed in terms of durability (by scratch testing) and relative silver content using glow discharge optical emission spectroscopy (GDOES). PMID- 22097581 TI - Kinetics of the formation of titanium oxynitride and nitride under the action of VUV, studied by means of ellipsometry. AB - Preparation of thin nanolayers (approximately 10 nm) with the required stoichiometry and minimal grain size is important for the development of nanostructures. The kinetics of the formation of titanium nitride and titanium oxynitride layers through nitridation of the titanium matrix was investigated in the present work. It was shown that the UV radiation causes an increase in nitridation rate, depending on radiation energy, within the studied range 4 to 21 eV. The investigation was carried out with the help of ellipsometry and independent methods: atomic force microscopy, electron microscopy, and X-ray photoelectron spectroscopy. The mechanism of titanium interaction with nitrogen resulting in the formation of nitride and oxynitride layers at the Si/Ti and SiO2/Ti interfaces was investigated, the role of the UV radiation in solid-state reactions was revealed, and the mechanism of the process was proposed on the basis of the experimental data and results of quantum chemical simulation. The use of UV radiation allowed us to obtain the layers at low temperatures (0-5 degrees C) and to achieve a short reaction time due to an increase in reaction rate. The resulting layers have good masking properties (minimal density of pores and defects, high smoothness of the surface). This allows one to use these layers for chemical and electronic passivation and stabilization of the surface of semiconductor nano-objects (quantum dots, quantum wires, nanowhiskers etc.) for electronic and photon nanodevices. PMID- 22097582 TI - Atomically controlled processing in silicon-based CVD epitaxial growth. AB - One of the main requirements for Si-based ultrasmall device is atomic-order control of process technology. Here, we show the concept of atomically controlled processing for group IV semiconductors based on atomic-order surface reaction control in Si-based CVD epitaxial growth. Self-limiting formation of 1-3 atomic layers of group IV or related atoms after thermal adsorption and reaction of hydride gases on Si(1-x)Gex(100) (x = 0-1) surface are generalized based on the Langmuir-type model. Moreover, Si-based epitaxial growth on N, P or C atomic layer formed on Si(1-x)Gex(100) surface is achieved at temperatures below 500 degrees C. N atoms of about 4 x 10(14) cm(-2) are buried in the Si epitaxial layer within about 1 nm thick region. In the Si(0.5)Ge(0.5) epitaxial layer, N atoms of about 6 x 10(14) cm(-2) are confined within about 1.5 nm thick region. The confined N atoms in Si(1-x)Gex preferentially form Si-N bonds. For unstrained Si cap layer grown on top of the P atomic layer formed on Si(1-x)Gex(100) with P atomic amount of below about 4 x 10(14) cm(-2) using Si2H6 instead of SiH4, the incorporated P atoms are almost confined within 1 nm around the heterointerface. It is found that tensile-strain in the Si cap layer growth enhances P surface segregation and reduces the incorporated P atomic amount around the heterointerface. Heavy C atomic-layer doping suppresses strain relaxation as well as intermixing between Si and Ge at the nm-order thick Si(1-x)Gex/Si heterointerface. These results open the way to atomically controlled technology for ULSIs. PMID- 22097583 TI - The effects of using ALD-grown ZnO buffer layers on the properties of indium tin oxide grown by chemical solution deposition. AB - In comparison to ITO films prepared by chemical solution deposition on bare substrates, the use of a ZnO buffer layer and Al2O3 barrier layer has been shown to have a significant effect on morphology, measured sheet resistance and therefore resistivity. In the case of quartz substrates, ITO resistivity decreased from 9.6 x 10(-3) ohms cm to 4.3 x 10(-3) ohms cm on incorporation of a ZnO buffer layer and Al2O3 barrier layer, both grown by ALD. A change in surface morphology was observed, due to the presence of the buffer layer, however, the ZnO buffer layer was not found to influence the XRD pattern of the ITO films. PMID- 22097584 TI - Aerosol assisted depositions of polymers using an atomiser delivery system. AB - The hydrophobicity, robustness and anti-microbial properties of Sylgard 184 polymer films deposited via AACVD were optimised by using aerosol droplets from an atomiser delivery system, polymer coating substrates and the swell encapsulation of methylene blue. By using an atomiser deposition system (average droplet size 0.35 microm) rather than a misting aerosol system (45 microm) lead to a surface with smaller surface features, which improved hydrophobicity (water contact angle 165 degrees) in addition to increasing the films transparency from ca 10 to 65%. Pre-treating the substrates with the same Sylgard 184 elastomer lead to a highly consistent surface hydrophobicity and an increase in average water contact angle measured (169 degrees). This paper shows the first example of dye incorporation in a CVD derived polymer film-these films have potential as antimicrobial surfaces. PMID- 22097585 TI - Influence of varying porogen loads and different UV cures on low-kappa film characteristics. AB - Nanoporous low-kappa films were manufactured by using a 3-step process: co deposition of a skeleton and porogens by PECVD, porogen removal by remote plasma and UV cure. In this study, the influence of both the variation of the porogen load and the different types of UV-cures on several film characteristics were investigated. Improved kappa-values were observed for increased porogen to skeleton ratios and a broad band cure, where the wavelength of the photons is always higher than 200 nm. However the Young's modulus and hardness decreased correspondingly. These variations can be attributed to the changing density and chemical composition of the different films. A wide range of low-kappa films was obtained by tuning the porogen load and applying different types of UV cures. PMID- 22097586 TI - A difference in using atomic layer deposition or physical vapour deposition TiN as electrode material in metal-insulator-metal and metal-insulator-silicon capacitors. AB - In this work, metal-insulator-metal (MIM) and metal-insulator-silicon (MIS) capacitors are studied using titanium nitride (TiN) as the electrode material. The effect of structural defects on the electrical properties on MIS and MIM capacitors is studied for various electrode configurations. In the MIM capacitors the bottom electrode is a patterned 100 nm TiN layer (called BE type 1), deposited via sputtering, while MIS capacitors have a flat bottom electrode (called BE type 2-silicon substrate). A high quality 50-100 nm thick SiO2 layer, made by inductively-coupled plasma CVD at 150 degrees C, is deposited as a dielectric on top of both types of bottom electrodes. BE type 1 (MIM) capacitors have a varying from low to high concentration of structural defects in the SiO2 layer. BE type 2 (MIS) capacitors have a low concentration of structural defects and are used as a reference. Two sets of each capacitor design are fabricated with the TiN top electrode deposited either via physical vapour deposition (PVD, i.e., sputtering) or atomic layer deposition (ALD). The MIM and MIS capacitors are electrically characterized in terms of the leakage current at an electric field of 0.1 MV/cm (I leak) and for different structural defect concentrations. It is shown that the structural defects only show up in the electrical characteristics of BE type 1 capacitors with an ALD TiN-based top electrode. This is due to the excellent step coverage of the ALD process. This work clearly demonstrates the sensitivity to process-induced structural defects, when ALD is used as a step in process integration of conductors on insulation materials. PMID- 22097587 TI - Low temperature SiC film deposition using trichlorosilane gas and monomethylsilane gas. AB - In order to produce silicon carbide thin film through the process entirely at low temperatures, silicon carbide chemical vapor deposition on a silicon wafer surface was performed using trichlorosilane gas and monomethylsilane gas. First, the silicon thin film was formed using trichlorosilane gas at 800 degrees C and was cooled to room temperature in ambient hydrogen, in order to produce hydrogen terminated silicon surface. Next, monomethylsilane gas was introduced at room temperature to produce silicon carbide thin film. The mirror-like appearance of the film obtained by this process was maintained after the exposure to hydrogen chloride gas at 800 degrees C. Furthermore, very thin Si-C layer was detected at the surface by means of the time-of-flight secondary ion mass spectrometry. Thus, the silicon carbide thin film was concluded to be formed through the process at temperatures below 800 degrees C. PMID- 22097588 TI - Atomic layer deposition of ruthenium films on strontium titanate. AB - Atomic layer deposition of ruthenium on SrTiO3 layers was investigated using (C2H5C5H4). (NC4H4)Ru and air as precursors. For comparison, the growth was studied also on ZrO2 films and SiO2/Si surfaces. Deposition temperature was 325 degrees C. Using rather short but intense air pulses, smooth and uniform Ru films were deposited on SrTiO3. The films were crystallized at early stages of the growth. The nucleation density and rate on SrTiO3 were notably lower compared to that on ZrO2 and SiO2, but the physical qualities including the film conductivity were considerably enhanced after reaching Ru film thickness around 10 nm. PMID- 22097589 TI - Conformal atomic layer deposition of TA-based diffusion barrier film using a novel mono-guanidinate precursor. AB - In this work, we present elaboration of Ta-based thin films by ALD from a novel tantalum precursor, the eta2-N,N'-isopropylethylguanidinato-tetra-diethylamino tantalum ([eta2-(i)PrNC(NEt2)NEt]Ta(NEt2)4, IEGTDEAT). Ammonia was used as reducing agents. The experimental conditions were optimized by quartz microgravimetry, studying the influence of duration of precursors and purge pulses and the substrate temperature. An optimal deposition temperature of 260 degrees C was showed. Ta-based thin films deposited on planar and patterned substrates showed a perfect conformality and continuity, even at low number of cycles. PMID- 22097590 TI - Amorphous alumina coatings: processing, structure and remarkable barrier properties. AB - Amorphous aluminium oxide coatings were processed by metalorganic chemical vapour deposition (MOCVD); their structural characteristics were determined as a function of the processing conditions, the process was modelled considering appropriate chemical kinetic schemes, and the properties of the obtained material were investigated and were correlated with the nanostructure of the coatings. With increasing processing temperature in the range 350 degrees C-700 degrees C, subatmospheric MOCVD of alumina from aluminium tri-isopropoxide (ATI) sequentially yields partially hydroxylated amorphous aluminium oxides, amorphous Al2O3 (415 degrees C-650 degrees C) and nanostructured gamma-Al2O3 films. A numerical model for the process allowed reproducing the non uniformity of deposition rate along the substrate zone due to the depletion of ATI. The hardness of the coatings prepared at 350 degrees C, 480 degrees C and 700 degrees C is 6 GPa, 11 GPa and 1 GPa, respectively. Scratch tests on films grown on TA6V titanium alloy reveal adhesive and cohesive failures for the amorphous and nanocrystalline ones, respectively. Alumina coating processed at 480 degrees C on TA6V yielded zero weight gain after oxidation at 600 degrees C in lab air. The surface of such low temperature processed amorphous films is hydrophobic (water contact angle 106 degrees), while the high temperature processed nanocrystalline films are hydrophilic (48 degrees at a deposition temperature of 700 degrees C). It is concluded that amorphous Al2O3 coatings can be used as oxidation and corrosion barriers at ambient or moderate temperature. Nanostructured with Pt or Ag nanoparticles, they can also provide anti-fouling or catalytic surfaces. PMID- 22097591 TI - Fluidized bed chemical vapor deposition of silicon on carbon nanotubes for Li-ion batteries. AB - Silicon was deposited on balls of entangled multi-walled carbon nanotubes (CNT) with a mean diameter of several hundreds of microns, by Fluidized Bed Chemical Vapor Deposition from silane (SiH4). The weight total percentage of deposited silicon was between 30 and 70%, to test their efficacy in Li-ion battery anodes. TEM and SEM imaging revealed that silicon deposits were of the form of nanoparticles uniformly dispersed on the whole CNT surface. The diameter of these nanoparticles increases with the deposited silicon percentage from 18 to 36 nm whereas their density remains constant at 5 10(22) nanoparticles/g of CNT. This indicates a low affinity of chemical species born from silane pyrolysis with the CNT surface for nucleation. The increase of the silicon nanoparticles diameter leads to the decrease of the specific surface area and the porous volume of the balls, probably due to the filling of the pores of the CNT network by silicon. A slight increase of the mean diameter of the balls was observed for the two highest silicon percentages, certainly due to the ability of the CNT network to be deformed under the mechanical stress induced by the silicon nanoparticles growth. PMID- 22097592 TI - Single-step fabrication of nanolamellar structured oxide ceramic coatings by metal-organic chemical vapor deposition. AB - Oxide ceramic coatings in the system Y2O3-Al2O3-ZrO2 were fabricated in laboratory scale by using a MOCVD unit. A hot wall reactor was used along with different precursor feeding systems. Most experiments were carried out by using powder flash evaporation including a screw feeder for precursor powder delivery. For comparison, further samples were fabricated by using band flash evaporation and continuous evaporation from a crucible. Oxygen was used in all cases as reactant gas. Aluminium-tris-2,4-pentanedione (Al(acac)3), yttrium-tris-2,2,6,6 tetramethyl-3,5-heptanedione (Y(thd)3) and zirconium-tetrakis-2,2,6,6-tetramethyl 3,5-heptanedione (Zr(thd)4) were applied as metal-organic precursors because of their similar vaporization behaviour under the given conditions. The coating stoichiometry was varied from pure alumina to complex ternary compositions in the system Y2O3-Al2O3-ZrO2. Both kinds of ternary coatings fabricated by using flash evaporation methods show a nanolamellar microstructure in the as deposited state. Heat treating experiments at 1200 degrees C for up to 5 days enhance the lamellar character of the coating deposited by using powder flash evaporation. The lamellar microstructure is due to alternating YSZ enriched layers and YAG enriched layers in this state. However, the coating fabricated by using band flash evaporation shows a dense interpenetrating network of YSZ and YAG after heat treating instead of a lamellar microstructure observed in the as deposited state. PMID- 22097593 TI - Non-thermal atmospheric pressure plasma etching of F:SnO2 for thin film photovoltaics. AB - Thin film based photovoltaic systems offer significant advantage over wafer based technologies enabling the use of low cost, large area substrates such as glass, greatly facilitating the construction and integration of large modules. The viability of such systems has advanced in recent years, with researchers striving to optimise performance through the development of materials and cell design. One way to improve efficiency is to texture the interface between the TCO and the absorber layer to maximise scattering over the appropriate wavelength range, with nanometre scale features such as pyramids being reported as giving high scatter. These textures may be achieved by advanced growth processes, such as CVD, post growth etching or a combination of both. In this work, textured F:SnO2 films produced by APCVD were favourably modified using a remote, non thermal, atmospheric plasma to activate a selective dry etch process resulting in significantly enhanced topography. Uniform treatment of the samples was achieved by translation of the samples below the plasma head. Advantages of this approach, compared to competitive technologies such as wet chemical processes, are the relatively low power consumption and ease of scalability and retroprocess integration. The modified structures were studied using AFM, SEM and EDAX, with the observed topography controlled by process variables. Optical properties were assessed along with Hall measurements. PMID- 22097594 TI - Impedance spectroscopy of manganite films prepared by metalorganic chemical vapor deposition. AB - Polycrystalline Pr(1-x)CaxMnO3 (PCMO) films were prepared by liquid source metalorganic chemical vapor deposition using in situ infrared spectroscopic monitoring. The electric properties of the PCMO-based devices with Ni and Al electrodes (Ni-PCMO-Ni and Al-PCMO-Al devices) were studied by dc current-voltage (I-V) measurements and ac impedance spectroscopy. The current varied linearly with the applied voltage in Ni-PCMO-Ni devices, while nonlinear behavior was observed in I-V curves for Al-PCMO-Al devices. Impedance spectra were also different between Ni-PCMO-Ni and Al-PCMO-Al devices. The Cole-Cole plots for the Ni-PCMO-Ni devices showed only a single semicircular arc, which was assigned to the PCMO bulk impedance. Impedance spectra for the Al-PCMO-Al devices had two distinct components, which could be attributed to the PCMO bulk and to the interface between the PCMO film and the Al electrode, respectively. The bias dependence of the impedance spectra suggested that the resistance switching in the Al-PCMO-Al devices was mainly due to the resistance change in the interface between the film and the electrode. The metal electrode plays an important role in the resistance switching in the PCMO-based devices. The choice of the optimum metal electrodes is essential to the ReRAM application of the manganite-based devices. PMID- 22097595 TI - Carburization of Si microwires by chemical vapour deposition. AB - We report the elaboration of silicon carbide (SiC) nanostructures thanks to the carburization of silicon microwires (MWs) under methane at high temperature. The produced SiC nanostructures display a tubular shape and are polycrystalline. The as-prepared silicon carbide microtubes (MTs) were characterized and studied by scanning electron microscopy (SEM), dual focused ion beam-scanning electron microscope (FIB-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and Raman spectroscopy. The formation of microtubes can be explained by the out-diffusion of Si through the SiC during the carburization process. PMID- 22097596 TI - Atmospheric pressure chemical vapor infiltration (CVI) for the preparation of biomorphic SiC ceramics derived from paper. AB - Chemical Vapor Infiltration of biological structures such as paper is used here to produce biomorphic SiC ceramics with high temperature resistance. The biological substrate materials are infiltrated with tetramethylsilane (TMS) at atmospheric pressure and elevated temperatures of 790 degrees C. A simple tube furnace (hot-wall reactor) is used for the infiltration process. As result, porous SiC-ceramics are grown which are around 20% smaller and 70% lighter than the initial substrates. This can be explained by the pyrolytic reaction of the substrates while heating them up to 790 degrees C, which is necessary for the infiltration process. Nevertheless, besides the shrinking of the substrates the geometrical form remains nearly unchanged. The resulting materials were heated up to 1000 degrees C in oxygen atmosphere in order to analyze their resistance against oxidation. After this treatment, all of them were still mechanically stable and of unchanged shape while a further mass loss was observed. This confirms the high temperature stability of the prepared materials. PMID- 22097598 TI - [Difference of HBV DNA levels and HBV genotypes between the patients with primary hepatocellular carcinoma and liver cirrhosis with hepatitis B]. AB - OBJECTIVE: To compare the difference of HBV DNA levels and HBV genotypes between the patients with primary hepatocellular carcinoma (HCC) and liver cirrhosis who infected with hepatitis B virus. METHODS: Total 430 patients with hepatitis B were enrolled and further divided into the HCC group (210 cases) and liver cirrhosis group (HBV LC, 220 cases). The levels of HBV DNA and HBV genotypes were detected in all of the serum samples from the two groups, and the differences in the genotypes and virological markers between HCC patients and HBV LC patients were further analyzed. RESULTS: The positive rates of HBV DNA of HCC patients and HBV LC patients were 84.3% (177/210) and 94. 5% (208/220), respectively. The mean values of serum HBV DNA in HCC patients and HBV-LC patients were (5.06 +/- 1.01) log10 cps/ml and (5.36 +/- 1.13) log10 cps/ml, respectively. The positive rates of HBV DNA and the mean values of serum HBV DNA were higher in HBV-LC patients than those in HCC patients (P < 0.01). Furthermore, the main genotype was C in both groups and the distribution of genotype C and genotype B had no statistical difference. CONCLUSIONS: Mainly presented as a C genotype in both groups, the total levels of serum HBV DNA in HCC patients were lower than those in HBV-LC patients. PMID- 22097597 TI - [Detection and analysis of gene polymorphism in hepatitis B virus C region]. AB - OBJECTIVE: To explore the variations of gene C in hepatitis B viruses between hepatitis B patients and healthy carriers, and provide experimental evidences for analysis of virus gene mutations acting on the virus material science and response of the body to the virus. METHODS: The virus DNA load in hepatitis B patients and healthy blood donors was investigated by real-time polymerase chain reaction (PCR). Gene sequence analysis was taken to detect gene polymorphism, and all the success samples were compaired with standard strain by DNAstar. RESULTS: (1)G Compared with standard strain, C region in all samples had mutations, there were 31 mutations in at least 2 samples (3 mutations in gene PreC and 28 mutations in gene C), including 9 missense mutations, 1 chain termination mutation and 21 synonymous mutation. Mutations nt 1827 c-->a and nt 2221 c-->t existed in all the samples, and most samples had 6 synonymous mutations. Four hepatitis B patients had mutation nt1896 g-->a, and another 4 patients had 2 mutations, namely, S87G and I97F (or 197L) in HBcAg CTL recognition episome. (2) The success ratio of amplification and sequencing of HBV DNA was closely associated with its copy numbers. In the present study, copy numbers of HBV DNA which were successfully amplified and sequenced were almost more than 40 193/ml. CONCLUSIONS: HBV genome were easily affected by nucleotide mutations, 2 residues had mutations in gene of C region, which is firstly reported, suggesting these mutations may be geographical restricted. Mutations in gene of C region may either change the structure and function of HBeAg and HBcAg, which may further induce the escape of immune clearance for HBV or influence the detection of HBsAg or HBeAg, which may creat new problems for the prevention, diagnosis and treatment of hepatitis B. PMID- 22097600 TI - [Analysis of sequence and genotype of E gene of the newly isolated Japanese encephalitis virus strains in Wuhan, Hubei Province]. AB - OBJECTIVE: To analyze the molecular characteristics of the newly isolated two Japanese encephalitis virus strains (JEV) in Wuhan. METHODS: The mosquitoes were collected in Wuhan from April to October in 2009. The envelope (E) protein gene of JEV was detected using RT-PCR and sequenced. Sequence comparisons and phylogenetic analysis were conducted using DNAstar and MegAlign. RESULTS: Two Japanese encephalitis virus (JEV) strains (WHJX09-9, WHJX09-10) were isolated from Culex tritaeniorhynchus among 16 mosquito pools and identified as genotype I. The result showed that the homology of the two strains was 98. 9% in nucleotides and 100% in deduced amines. The comparison between the new genotype 1 JEV strains and live attenuated vaccine strain SA14-14-2 in E gene showed that the homology of nucleotide sequence was 87.4% and 87.9%, the homology of amino acid was 96.9% (total 15 amino acid were different) in E gene. The mutation sites of amino acid distributed among three different coding domain, but no antigen binding site and neurotoxin-involved site of amino acid were changed. CONCLUSION: Wuhan had appeared a new genotype of JEV which was different from the former strain isolated in Wuhan, the new JEV strains still had neurotoxicity but had high homology with the vaccine strains adopted in Wuhan. The vaccine could still be adopted to prevent Japanese encephalitis if steps were take to eradicate mosquitos at the same time. laboratory surveillance were also an important task to build an early-warning mechanism against JEV. PMID- 22097599 TI - [Analysis of genetic diversity and amino acid sequence of HIV-1tat in CNS and peripheral tissue of a patient with ADC and a patient with non-ADC]. AB - OBJECTIVE: To study the diversity of HIV-1 tat gene in CNS and peripheral tissue of a patient with ADC and a patient with non-ADC, so as to research HIV evolution, the mechanism of CNS invasion and the pathogenesis of ADC. METHODS: The tat gene was amplified with nested PCR from genomic DNA which was extracted from spleen and basal ganglia of one non-ADC patient with a wide range of cerebral artery atherosclerosis and one ADC patient. PCR products were cloned into the PGEM-T vector, after transformation and selection by ampicillin and blue/white spotting. Five of positive clones were sequenced. HIV-1 tat sequences were processed with BioEdit and MEGA4. With the softwares, neighbor-joining tree, p-distances, values of ds/dn, and analysis of amino acid motifs were all done, so as to research the diversity of HIV-1 tat gene in CNS and peripheral tissue. RESULTS: Gene mutation of HIV-1 tat exist in the two patients, the mutation process of tat isolated from ADC patient suffered more compartmentalization than tat isolated from non-ADC patient, the differences of tat genes between CNS and peripheral tissue in ADC patient were greater than the non-ADC patient. Ds/dn showed that the virus gene mutation played a major role, the body intend to remove harmful non-synonymous mutations. CONCLUSIONS: The compartmentation of tat gene in CNS and peripheral tissue of the two patients was different, the reason may be related to the pathway of HIV into the CNS, the relationship between HIV gene mutation in CNS and ADC still need more investigation. PMID- 22097601 TI - [Human cytomegalovirus glycoprotein B genotypes in congenitally infected neonates]. AB - OBJECTIVE: To investigate human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes and clinical features in neonates with congenital infections. METHODS: Urine samples were obtained from 67 neonates with HCMV infection confirmed by polymerase chain reaction (PCR). The gB gene fragment was amplified by nested PCR. HCMV gB genotyping was detected by restriction fragment length polymorphism. RESULTS: In all these cases, the most prevalent genotype was gBl (50.7%), followed by gB3 (23.9%), gB2 (17.9%), and gBl/gB3 coinfection (7.5%); gB4 was not found. Moreover, gB1 was more prevalent in infants with liver damage (27/37, 73.0%) than in other symptomatic infants without liver damage (13/30, 43.3%; P < 0.05). CONCLUSION: The gBI genotype is the most prevalent in infants with congenital symptomatic HCMV disease, especially in those with liver damage, followed by genotypes gB3, gB2, and gB4. PMID- 22097602 TI - [The clinical research of the MGMT expression levels in glioma pations]. AB - OBJECTIVE: To investigate the correlation between the expression of tumor O (6) methylquanine DNA methyl-tranferase(MGMT) and pathological grade,and the influence of racial factors on tumor MGMT expression levels for glioma patients. METHODS: Compare and analysis the correlation between the pathological grade and MGMT levels and the racial factors on MGMT expression levels by the immunohistochemical staining on the tumor specimens of 33 Uygur and 61 Han. RESULTS: The positive rate of 61 Han gliomas pations with MGMT is 45.90% and 33 cases of the Uygur is 30.30% , there's no clear correlation between the racial factors and the tumor MGMT levels. (P >0.05). Comparative the 94 patients with pathological level and tumor MGMT level, there is no clear correlation between pathologic level and MGMT pression in tumor tissues (P >0.05). CONCLUSION: There's no clear correlation of tumor MGMT expression and pathological levels; and there's no significant effect between racial factors and expression of glioma MGMT. PMID- 22097603 TI - [Sequencing and analyses of the adenovirus polymerase gene in fecal samples of captively bred Rhesus macaques]. AB - OBJECTIVE: In an attempt to study the moleculr characterization and epidemiology of simian adenoviruses in nonhuman primate (NHP) populations. METHODS: We examined a colony of captively bred rhesus macaques (Macaca mulatta) in China for the presence of adenoviral DNA in stool samples. This was done by using the PCR method that targeted the adenovirus polymerase gene, and the PCR positive fragments were cloned for sequencing and phylogenetic analyses. RESULTS: Among the 57 animals analyzed, fecal samples from 12 animals were positive for the presence of adenoviral DNA. The results suggested that the viral DNA clones were primarily segregated into two large groups: SAdV-6 (2 non-redundant sequences) and SAdV-7 (9 non-redundant sequences). In addition, there were three clones with more similarity to SAdV-1, SAdV-3 and HAdV-52 respectively. CONCLUSION: Our data confirmed the prevalence of adenoviral DNA in the feces of NHPs and revealed the adenoviruses in the gastrointestinal tract of the study animals. heterogeneity and phylogenetics of the adenoviruses in the gastrointestinal tract of the study animals. PMID- 22097604 TI - [The correlational study of viral load of human bocavirus and clinical features in children with acute respiratory tract infection]. AB - OBJECTIVE: To analyze the correlations between clinical features in paediatric patients with acute respiratory tract infection (ARTI) and viral load of human bocavirus. METHODS: A prospective study was conducted on 956 children < 5 years admitted with an acute respiratory tract infection from November 2009 to December 2010, and 251 healthy children conclused as control group in the corresponding period. Human bocavirus was investigated in nasopharyngeal aspirates (NPA) and throat swab by PCR, and viral load was detected by real-time polymerase chain reaction (RT-PCR) in HBoV positive sample. Clinical data were also prospectively recorded. RESULTS: A significant difference was found in HBoV positive rate between children with ARTI and control group at enrollment. There was a significant difference in HBoV viral load between children with upper respiratory tract infection and lower respiratory tract infection. HBoV viral load did not differ significantly between children with upper respiratory tract infection and control group. Among children with lower respiratory tract infection, no significant difference were detected between common and severe cases in HBoV viral load. HBoV viral load did not differ significantly whether the children were with or without co-infection. CONCLUSIONS: HBoV could be detected perennial and considered as a major pathogen associated with acute respiratory tract infection in children. However, HBoV may not be a independent factor in children with ARTI and the HBoV viral load was not associated with the severity of respiratory illness. PMID- 22097605 TI - [The analysis of effect of Th1/Th2 cytokine in the different prognosis in severe influenza A (H1N1)]. AB - OBJECTIVE: To explore the effect of cytokine in the different prognosis of patients with severe influenza A (H1N1) infection. METHODS: 28 cases with severe influenza A (H1N1) were enrolled in the study including 16 cured cases and 12 dead cases. The cytokine level in serum was detected by Luminex technology. RESULTS: The levels of IL-2, IL-12 (P70) and IFN-gamma in dead group was lower than cured and normal control group and the difference were significant, P <0.05, respectively. IL-4 level in the dead group was significantly lower than cured group and normal control group, P value was 0.0310 and 0.0012, respectively. CONCLUSIONS: The Thl cytokine level in the severe 2009 epidemic H1N1 influeaze cases shows decreased trend, and the trend is more obvious in dead cases. The decrease of Th1 cytokine may be one of reasons leading to severe clinical situation and related withthe bad prognosis. PMID- 22097606 TI - [Study on EB virus infection, LMP1 and Bcl-2 expression in lung cancer patients]. AB - OBJECTIVE: To investigate the Epstein-Barr virus (EBV) infection, the expression of EBV latent membrane protein 1 ( LMPl) and oncogene bcl-2 in lung cancer patients. METHODS: EBERI in 108 cases of lung cancer were detected with in situ hybridization. EBV positive and negative lung cancer tissues were analysed for the expression of LMP1 and Bcl-2 by immnohistochemistry. The average area (AA) and integral optical density (IA) of each sample was measured with the digital medical image analyzing system. RESULTS: In 108 cases of lung cancer, 36 cases were EBER1 positive and 7 cases were LMP1 positive. The expression of Bcl-2 was higher in EBV positive lung cancer tissues than that in EBV negative. The AA value was 58014.23 +/- 6918.45 and 38156.22 +/- 4096.79, while the IA value was 11.00 +/- 1.48 and 8.03 +/- 0.78 respectively. No statistic difference was fund in the expression of Bcl-2 betwen LMP1 positive and negative lung cancer tisssues. CONCLUSION: EBV infection in lung cancer increased the expression of bcl-2, which may play a role in the occurrence or development of lung cancer. The increased expression of Bcl-2 may not be induced by LMP1. The exact mechanism need further study. PMID- 22097607 TI - [The expression and bioactivity of S gene in Vero-E6 cells using baculovirus vector]. AB - OBJECTIVE: The S gene of a Hanta Virus (HV) Z10 strain was cloned into a baculovirus shuttle bacmid pDual-CMV contained a CMV promoter to generated a recombinant baculovirus BAC-pDual-CMV-HVS, then the recombinant baculovirus was transfected into Vero-E6 cell. The cells with recombinant baculovirus were applied to the detection of HV antiserum. METHODS: To generate the recombinant baculovirus BAC-pDual-CMV-HVS, the sequence of CMV promoter was obtained from the plasmid pEGFP-N1 by PCR, and subsequently cloned to the baculovirus shuttle bacmid pFastBacDUAL resulting the recombinant plasmid pDual-CMV. Then the sequence of HV-S gene was inserted to the plasmid pDual-CMV, to generate the plasmid pDual-CMV-HVS. Plasmid pDual-CMV-HVS was transformed into the DH10BAC competent cells to get the recombinant baculovirus BAC-pDual-CMV-HVS. The antigen substrate slides were made by transfecting the recombinant virus into Vero-E6 cells. RESULTS: The plasmid pDual-CMV-HVS was verified by sequencing. The recombinant virus BAC-pDual-CMV-HVS was generated according to the protocol of the baculovirus and transfected into Vero-E6 cells. The expression of the HV-S gene was verified by positive HV antiserum. CONCLUSION: [corrected] The recombinant virus were successfully generated and applied to prepare the antigen substrate slides. The antigen substrate slides was conveniently prepared without special equipments, and can be used to detect the antiserum of HV virus. PMID- 22097608 TI - [Clinical study on viral hepatitis combined with aplastic anemia]. AB - OBJECTIVE: To study the clinical features, outcomes and treatments of viral hepatitis combined with aplastic anemia. METHODS: 25 cases diagnosed as viral hepatits combined with aplastic anemia in Beijing Ditan Hsopital between April 2004 and September 2009 were retrospectively analyzed. In this group of patients aplastic anemia was finally diagnosed by bone marrow aspiration. We collected clinical data of these patients, including a history of liver disease, drug allergies, hospital medication history, laboratory data, and then performed descriptive analysis. RESULTS: 25 patients with viral hepatitis were diagnosed as complicated with aplastic anemia by histopathological data. Among these patients, 17 were male and 8 were women. Viral hepatitis included: chronic hepatitis B (12 cases), chronic hepatitis C (4 cases), acute hepatits E (1 case), hepatitis caused by CMV infection (1 case), and unclassified hepatitis (7 cases). Among these patients, 7 were diagnosed as severe hepatits. Considering previous history, only 3 patients had history of short term interferon therapy before hospitalization, and the remaining patients did not use drug that affects blood system. Treatments were as followings: using colony stimulating factor in 6 patients, gamma globulin in 9 patients, glucocorticoids in 3 patients, erythropoietin in 1 patient, only oral drug to raise erythrocytes in 2 patients, red blood cells transfusion in 6 patients, platelets transfusion in 2 patients. As for clinical outcomes, 20 patients acquired improved condition and were dicharged, 3 patients were discharged voluntarily and 2 patients died of severe hepatits combined with other complications. CONCLUSION: Main treatments of viral hepatitis combined with aplastic anemia were to treat primary hepatopathy and nucleoside analogue-based antiviral therapy, to provide symptomatic and supportive treatment for blood diseases. Blood diseases would recover simultaneously while liver disease was improved, and the prognosis was good. PMID- 22097610 TI - [The clinical epidemiology characteristics of HFMD in 2010 of Hangzhou]. AB - OBJECTIVE: To analyze clinical epidemiology characteristics of HFMD in children from April 2010 to October in Hangzhou. METHODS: 1848 HFMD hospital patients are admitted to clinical epidemiological analysis. RESULTS: Onset ages of HFMD primarily under 3 years, boys more than girls, social above diasporas, rural above town. The highest peak in 5-7 months. Mostly clinical symptoms are mild, the prognosis is good. CONCLUSION: HFMD has obvious susceptible population and susceptibility season. Increase health interventions to susceptible regions and the crowd in popular season, early detection, active therapy, most prognosis is good. PMID- 22097609 TI - [Significance of serum golgi protein 73 (GP73), alpha-fetoprotein (AFP) and lectin-reactive alpha-fetoprotein (AFP-L3) expresssion in primary hepatic carcinoma]. AB - OBJECTIVE: To explore the alone and joint diagnostic value of serum golgi protein 73 (GP73), alpha-fetoprotein (AFP) and the percentage of lectin-reactive aipha fetoprotein (AFP-L3) of primary hepatic carcinoma (PHC), and provide a novel method for diagnosis for PHC and screening for high-risk population. METHODS: ELISA was used to detect the serum level of GP73, AFP and AFP-L3% in 81 cases of PHC,176 cases chronic hepatitis and liver cirrhosis, 30 cases other tumber cancer and 40 cases of health people. RESULTS: The sensitivity of GP73, AFP and AFP-L3% in PHC is 77.78%, 62.69% and 51.85%, and the specificity is 84.55%, 86.99% and 96.34%, respectively. Joint detection could increase the sensitivity up to 88.89%. CONCLUSION: GP73 was a high sensitivity mark for dignosis of PHC, while AFP-L3% was a high specificity mark for dignosis of PHC. The joint detection could improve PHC diagnostic performance. PMID- 22097611 TI - [Detection the serum IgM and IgG specific for TORCH in 1307 women in the period of pre-pregnancy and pregnancy]. AB - OBJECTIVE: The objective is to obtain the information of women in the period of prepregnancy and pregnancy infected by TORCH (Toxoplasma, Rabella Virus, Cytomegalovirus, and Herpes Simplex Virus) in Kunming for preventing fetus from infection by TORCH in uterus. METHODS: The serum IgM and IgG specific for TORCH from 1307 women in the period of pre-pregnancy and pregnancy were measured with ELISA and The reagent is the product of virion/serion. RESULTS: The serum IgM specific for TORCH were detected in 2.83% of 1307 pregnant women for Toxoplasma, 2.37% for Rebulla Virus, 0.46% for Cytomegalovirus, 2.45% for Herpes Simplex Virus. The total positive rate of serum IgM specific for TORCH was 1.45%. The serum IgG specific for TORCH were detected in 3.98% of 1307 pregnant women for Toxoplasma, 72.3% for Rebulla Virus, 97.78% for Cytomegalovirus, 80.34% for Herpes Simplex Virus. The total positive rate of serum IgG specific for TORCH was 63.60%. There was no significant difference among the women with different pregnant situation in terms of the serum IgM and IgG specific for TORCH. CONCLUSION: There are some of women in the period of pre-pregnancy and pregnancy with current infection by TORCH in Kunming. It is recommended to screen for infection by TORCH in women in the period of pre-pregnancy and pregnancy to prevent fetus from infection by TORCH in uterus. PMID- 22097612 TI - [Efficacy of two nucleoside analogs to treat resistant HBeAg-negative chronic hepatitis B]. AB - OBJECTIVE: To observe the therapeutic effect and safety of entecavir and adefovir in the treatment of lamivudine-resistant HBeAg-negative chronic hepatitis B. METHODS: Sixty-five patients with lamivudine-resistant HBeAg-negative chronic hepatitis B were randomly divided into two groups. The entecavir treatment group included 33 patients, who were administrated entecavir 1.0 mg/d. The adefovir treatment group included 32 patients, who were administrated adefovir dipivoxil 10 mg/d. Changes in serum HBV DNA, liver functions, phosphocreatine kinase, creatinine and adverse reaction were dynamically monitored. RESULTS: At the end of the 12th, 24th, 48th week of treatment, the rates of serum ALT normalization of the entecavir treatment group were higher than that of the adefovir treatment group, but there wasn't statistically difference between two groups until the end of the 48 th week of treatment (P > 0.05). The rate of sera to turn negative for HBV DNA of the entecavir treatment group was significantly higher than that of the adefovir treatment group at the end of the 12th week. Moreover, the difference was statistically significant (P<0.05). CONCLUSION: Both entecavir and adefovir dipivoxil might have a good response to lamivudine-resistant HBeAg negative chronical hepatitis B. Entecavir could achieve better therapeutic effects. PMID- 22097613 TI - [The study of combining high-risk human papillomavirus types checking and cytologic test in the screening of cervical lesions]. AB - OBJECTIVE: To study the relationship between thinprep cytologic test and the types of human papilloma virus (HPV) infection in cervical precancerous lesion screening. METHODS: To perform high-risk HPV types test in 1375 samples. Choose 256 positive samples to take thinprep cytologic test (TCT) and directed biopsies under colposcopy. Adopting two-channels real time PCR to genotype and quantify eight high risk HPV DNA (high risk types: HPV 16, 18, 45, 31; intermediate risk types: HPV 33, 52, 58, 67). RESULTS: There are 256 positive samples in High risk HPV DNA test (18.62%). WNL rate for TCT is 16.41% (42/256), ASCUS and above rate for TCT is 83.59% (214/256). There is no statistically significant difference in the viral loads of HPV infection rate between the TCT negative patients and positive patients (P > 0.5). Positive correspondence rate for TCT and biopsy are 92.86% (39/42), 81.36% (48/59), 85.19% (23/27) and 9/10. CONCLUSION: High-risk HPV types checking combined with TCT and biopsy can raise positive rate significantly. It should be used as a reliable method for early diagnosis in cervical cancer and CIN screening. PMID- 22097615 TI - [Detection of hepatitis C core antigen in intravenous drug addictions]. AB - OBJECTIVE: To study the status of detection of hepatitis C core antigen in intravenous drug addictions, and discuss the foreground of the hepatitis C core antigen ELISA test system. METHODS: HCV core antigen, HCV RNA quantity, anti HCV IgG, HBsAg were analysis in all the plasma samples taken from 93 cases of intravenous drug users. RESULTS: The specialty and sensitivity of HCV core antigen in intravenous drug addictions 100% -54% separately. When HBsAg were positive, the sensitivity of HCV core antigen was 38%, while HBsAg negative, the sensitivity of HCV core antigen was 69% (P < 0.01). CONCLUSION: The detections of HCV core antigen showed high specialty but low sensitivity in intravenous drug addictions. The positive rate has positive relation with HCV RNA virus logarithm quantity. Coinfection with HBV are the interfere factor of HCV core antigen detection. In screening experimentations, the detection of HCV core antigen in plasma may be applied as supplement method for anti-HCV-IgG. It can also be used to monitor viremia in HCV infection. PMID- 22097616 TI - [Establishment and application of nested real-time quantitative polymerase chain reaction assay for detection of hepatitis B virus covalently closed circular DNA]. AB - OBJECTIVE: To establish a nested real-time quantitative polymerase chain reaction (PCR) assay for detection of hepatitis B virus covalently closed circular DNA in PBMC( peripheral blood monocyte) and MMNC (marrow monocyte). METHODS: Based on the structural differences between HBVcccDNA and HBV rcDNA, two pairs of specific primers spanned the gap of the positive and negative chains and a specific TaqMan probe situated downstream were designed. To remove rcDNA, cccDNA was processed by Mung Bean Nuclease,and then amplified by nested real-time quantitative PCR using a pair of outer primers and a pair of inner primers. According to the standard preparation, cccDNA levels of specimen were calculated. RESULTS: We have established a nested real-time fluorescent quantitative PCR method for HBV cccDNA successfully, and the linear range is from 5.0 x 10(2) to 3. 9 x 10(7) copies per milliliter. Of the 25 PBMC samples and 7 MMNC samples of the chronic hepatitis B or liver cirrhosis patients, 3 MMNC samples and 9 PBMC samples were HBV cccDNA positive, while all of the 21 healthy donator blood PBMC samples were negative. CONCLUSIONS: The nested real-time fluorescent quantitative PCR method may be applied to detect HBVcccDNA level in PBMC and MMNC. HBVcccDNA can be detected in PBMC and MMNC. PMID- 22097614 TI - [Comparative study on the clinical characteristics of HBV/HCV co-infection patients with different HCV contaminnation mode]. AB - OBJECTIVE: The purpose of this study was to compare the epidemiological, biochemical and virological characteristics among patients co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the mode of HCV contamination. METHODS: The study included 133 patients with chronic HBV/HCV co infection. They were studied and subdivided into two groups (drug addicts group and Blood transfusion group) according to the mode of HCV contaminnation. The epidemiological, biochemical and virological characteristics were collected. Univariate analysis was performed with the SPSS 16.0. RESULTS: 78 patients were infected by the mode of drug addicts (IDU), whereas 55 were infected by the mode of blood transfusion( PTCH). Patients in drug addicts group had yonger age, shorter HBV and HCV infection history, and lower cirrhosis percentage than those of patients in PTCH group (P <0.05). However,serum levels of ALT (t =4.760, P =0.000), AST (t = 3.798, P = 0.000), TBil (t = 4.274, P = 0.000) of IDU patients were higher than those of PTCH patients. There was difference of sex composition between two groups (chi2 = 18.706, P = 0.000). CONCLUSIONS: The clinical characteristics of patients with HBV/HCV coinfection were significantly different among different HCV contamination mode. PTCH patients have the characteristics of older age, more cirrhosis and mild degree of liver injury; IDU patients have the characteristics of yonger age,fewer cirrhosis and severe liver injury. PMID- 22097618 TI - [Soft tumors in the mid abdomen and thighs. Diabetes, lipohypertrophy]. PMID- 22097617 TI - [Establishment of cellular immunity of enhanced hepatitis B vaccine]. AB - OBJECTIVE: To establish the method to detect the cellular immune response of enhanced hepatitis B vaccine and make verification preliminary. METHODS: Immunized BALB/c mice with enhanced hepatitis B vaccine and detected the IFN gamma spots forming cells (SFC) of mouse spleen cell by Elispot. Optimized the conditions of the experiment. Cellular immune response between enhanced hepatitis B vaccine and normal hepatitis B vaccine by Elispot were compared. RESULTS: IFN gamma SFC was higher in 5microg dose than in 2microg dose after immunization with enhanced hepatitis B vaccine and IFN-gamma SFC was declined after immunization 3 weeks ago. IFN-gamma SFC was higher in stimulus by peptide than by protein. Compared to normal hepatitis B vaccine, IFN-gamma SFC was higher in enhanced hepatitis B vaccine. CONCLUSION: Established the detection method to evaluate the cellular immunity of enhanced hepatitis B vaccine and tested the repeatability. PMID- 22097619 TI - ["Enormous burden" of psychiatric illnesses (interview by Thomas Muller)]. PMID- 22097620 TI - [Is life insurance really worth it? The guaranteed interest rate and what remains]. PMID- 22097621 TI - [Early symptoms of systemic illnesses]. PMID- 22097622 TI - [Acute chest pain. A myocardial infarct - or does it come from the aorta?]. PMID- 22097623 TI - [The immunocompromised patient: can you vaccinate him? You even must!]. PMID- 22097624 TI - [The ghost ride ended in neurosurgery]. PMID- 22097625 TI - [When can he lift again?]. PMID- 22097628 TI - [Medical treatment of professional voice users]. PMID- 22097627 TI - [Medicine for musicians]. PMID- 22097629 TI - [Musicians dystonia]. PMID- 22097630 TI - [Diagnosis and therapy of performance anxiety]. PMID- 22097631 TI - [Fracture of the clavicle]. PMID- 22097632 TI - [Overweight in families with migrant background]. PMID- 22097633 TI - [Crohn's disease--early immune-modulatory therapy improves outcome]. PMID- 22097634 TI - [Too fat to be rescued?]. PMID- 22097635 TI - Multidimensional measure of display clutter and pilot performance for advanced head-up display. AB - INTRODUCTION: This study was conducted to: develop a multidimensional measure of display clutter for advanced head-up displays (HUDs) incorporating enhanced and synthetic vision; assess the influence of HUD configuration on perceptions of display clutter, workload, and flight performance; model clutter scores in terms of visual display properties; and model flight performance in terms of subjective and objective clutter indices. METHODS: In a flight simulator, 18 pilots with different levels of flight experience flew approaches divided into three segments. Three HUD configuration sets were presented under two levels of flight workload. Pilot ratings of overall display clutter, its underlying dimensions, and mental workload were recorded along with flight performance measures. Display image analysis software was used to measure visual properties of the HUDs. RESULTS: The multidimensional measure of clutter showed internal consistency with overall perceived clutter. Calculated clutter scores were sensitive to HUD configurations and in agreement with a priori display classifications. There was a trend for the extremes of display clutter to cause higher workload and less stable performance due to cognitive complexity and a lack of information for high and low clutter displays, respectively. Multiple linear regression models of perceived clutter were developed based on HUD visual properties with predictive utility. Models of flight performance based on the clutter score and workload ratings were also developed, but with less predictive power. DISCUSSION: Measures and models of display clutter are expected to be applicable to the evaluation of a range of display concepts. PMID- 22097636 TI - Axis rotation and visually induced motion sickness: the role of combined roll, pitch, and yaw motion. AB - BACKGROUND: Motion sickness (MS) is a well-known phenomenon in aviation and in virtual environments such as simulators or computer games. The severity of MS is thought to be due to the amount of sensory conflict, which should increase with the complexity of the simulated motion. The present study focused on the direction and complexity of simulated body rotations in the genesis and severity of visually induced MS. METHODS: Three simulated rollercoaster rides including translational movement in the fore-aft axis and additional rotational motion either in pitch only, along the pitch and roll axes, or in pitch, roll, and yaw were generated. We presented video clips of 15 min on a large projection screen to a total number of 61 volunteers, who were randomly assigned to 1 of the 3 rotational motion groups. MS was measured using the Fast Motion Sickness Scale (20-point verbal rating scale) and the Simulator Sickness Questionnaire. Aftereffects were captured up to 5 h after the experiment was finished. RESULTS: Analyses indicated lowest MS scores in the pitch-only condition (1.95). Dual- (4.33) or triple-axis (5.30) combinations revealed significantly higher MS scores than the single-axis condition, but surprisingly did not differ from each other. MS started to subside rapidly after about 1 h past stimulus presentation. DISCUSSION: We conclude that the complexity of visual motion does not increase MS linearly. Instead, we propose that MS reached a plateau in the dual-axis condition and adding a third rotational axis did not further surpass the severity of MS reached. PMID- 22097637 TI - Severe hypotension during the decreasing phase of Gz stress in anesthetized rats wearing an anti-G suit. AB - INTRODUCTION: Physiological responses to +Gz stress have been reported in several studies. However, no reports exist on differences in arterial pressure responses between increasing and decreasing G phases. We hypothesized that +Gz stress and/or an anti-G support might disturb the circulation system and cause potential brain hypoperfusion, even if the anti-G support protects against G-induced loss of consciousness. METHODS: Dependency of +Gz magnitude, hemodynamic changes, renal sympathetic nerve activity (RSNA), and aortic blood flow (AoBF) were estimated in anesthetized rats to analyze the effects of +Gz stress and/or an anti-G support on arterial pressure at a level of the brain (APLB). The rats were exposed to +Gz using a centrifuge for small animals while wearing an anti-G suit. RESULTS: APLB remained at the control level while the anti-G suit was inflated. However, a decrease in APLB was observed twice during increasing and decreasing G phases using the anti-G suit. Hypotension in the decreasing C phase at +5 Gz was significantly deeper than that in the increasing G phase (47.5 +/- 7.7 vs. 29.6 +/- 3.0 mmHg). RSNA responses to Gz loads were greater in the decreasing G than in the increasing G phase (129.7 +/- 8.6 vs. 147.3 +/- 10.4%). Both AoBF and calculated vascular resistance were suppressed more significantly in the decreasing G than in the increasing G phase (38.3 +/- 4.4 vs. 34.4 +/- 3.4 ml x min(-1), 1.44 +/- 0.22 vs. 1.09 +/- 0.14 mmHg x min(-1) x ml(-1)). DISCUSSION: We conclude that transient excessive decreasing G hypotension may occur during the decreasing G phase, which may be due to anti-G suit functioning. PMID- 22097638 TI - Automated collection of fatigue ratings at the top of descent: a practical commercial airline tool. AB - INTRODUCTION: There is a need to develop an efficient and accurate way of assessing pilot fatigue in commercial airline operations. We investigated the validity of an automated system to collect pilot ratings of alertness at the top of descent, comparing the data obtained with existing results from previous studies and those predicted by the validated SAFE fatigue model. METHODS: Boeing 777 pilots were prompted to enter a Samn-Perelli fatigue scale rating directly into the flight management system of the aircraft shortly prior to descent on a variety of short- and long-haul commercial flights. These data were examined to evaluate whether the patterns were in line with predicted effects of duty length, crew number, and circadian factors. We also compared the results with data from previous studies as well as SAFE model predictions for equivalent routes. RESULTS: The effects of duty length, time of day, and crew complement were in line with expected trends and with data from previous studies; the correlation with predictions from the SAFE model was high (r = 0.88). Fatigue ratings were greater on longer trips (except where mitigated by adding an extra pilot) and on overnight sectors (4.68 vs 3.77). DISCUSSION: The results suggest that the automated collection of subjective ratings is a valid way to collect data on fatigue in an airline setting. This method has potential benefits for the crew in assessing fatigue risk prior to approach, as part of a fatigue risk management system, with the possibility of wider safety benefits. PMID- 22097639 TI - Measuring the cumulative effect of G force on aviator neck pain. AB - INTRODUCTION: In many studies, high G force is thought to be the most important causal factor of aviator neck pain. However, most of the studies performed to date have compared neck pain of aviators exposed to high G force with that of aviators not so exposed or with that of the general population. As a result, neck pain for aviators exposed to high G force as it relates to G level is not yet well-known. METHODS: The subjects were 1003 male aviators who were sent an anonymous questionnaire. Subject variables were information on physical characteristics, lifestyle, and flight characteristics, including information about exposed maximum G (Gmax). There were three dependent variables: whether the aviator had experienced neck pain, frequency of neck pain, and subjective severity of neck pain. RESULT: With the multivariate analysis, amount of Gmax exposure (frequency or monthly duration of Gmax exposure) had a statistically significant positive relationship with all three dependent variable. BMI, flight hours in current aircraft, and posterior seat type had a meaningful positive relationship with experience of neck pain and subjective severity of neck pain. Other characteristics, including Gmax level, were not significantly related with any dependent variables. DISCUSSION: These results suggest that G level could have a ceiling effect; in other words, above a certain G level, aviator neck pain risk does not increase. This means that amount of Gmax exposure becomes more influential on aviator neck pain than the level of Gmax. PMID- 22097640 TI - Assessment of occupational cosmic radiation exposure of flight attendants using questionnaire data. AB - INTRODUCTION: Female flight attendants may have a higher risk of breast and other cancers than the general population because of routine exposure to cosmic radiation. As part of a forthcoming study of breast and other cancer incidence, occupational cosmic radiation exposure of a cohort of female flight attendants was estimated. METHODS: Questionnaire data were collected from living female cohort members who were formerly employed as flight attendants with Pan American World Airways. These data included airline at which the flight attendant was employed, assigned domicile, start and end dates for employment at domicile, and number of block hours and commuter segments flown per month. Questionnaire respondents were assigned daily absorbed and effective doses using a time weighted dose rate specific to the domicile and/or work history era combined with self-reported work history information. RESULTS: Completed work history questionnaires were received from 5898 living cohort members. Mean employment time as a flight attendant was 7.4 yr at Pan Am and 12 yr in total. Estimated mean annual effective dose from all sources of occupational cosmic radiation exposure was 2.5 +/- 1.0 mSv, with a mean career dose of 30 mSv. DISCUSSION: Annual effective doses were similar to doses assessed for other flight attendant cohorts; however, questionnaire-based cumulative doses assessed in this study were on average higher than those assessed for other flight attendant cohorts using company-based records. The difference is attributed to the inclusion of dose from work at other airlines and commuter flights, which was made possible by using questionnaire data. PMID- 22097641 TI - Laser illumination of flight crewmembers by altitude and chronology of occurrence. AB - INTRODUCTION: The illumination of flight crew personnel by lasers while they perform landing and departure maneuvers has concerned the aviation community for the past two decades. This study examines the frequency of illumination events in the United States by altitude and chronology of occurrence to determine where and when aviators and the flying public may be at greatest risk. METHODS: Reports of aircraft illuminated by high-intensity light sources are maintained in a database at the Federal Aviation Administration's Civil Aerospace Medical Institute. Reports of flight crewmembers exposed to lasers from January 1, 2004, to December 31, 2008, were collected and analyzed. RESULTS: Cockpit illuminations at or below 2000 ft (approximately 610 m) increased from 12.5 to 26.7% over the 5-yr period, while the percentage of illuminations between 2000 and 10,000 ft (approximately 610-3048 m) decreased from 87.5 to 58.4%. The months of November and December had the highest frequency of laser events (23%), while May and June had the least (12%). Sunday was the most likely day for an aircraft to be illuminated (18.3%), while Wednesday was the least likely day for such an incident (15.4%). More than 91% of all aircraft illumination events occurred between 1800 and midnight. CONCLUSION: The continuing increase in the number of laser illuminations reported at or below 2000 ft (approximately 610 m) represents an escalating threat to aviation safety. Information provided in this study may allow law enforcement to deploy their resources more efficiently to apprehend those responsible for these crimes. PMID- 22097642 TI - Irritable bowel syndrome: aeromedical considerations. AB - Irritable bowel syndrome (IBS) is a gastrointestinal disorder diagnosed in accordance with the Rome III criteria. The pathophysiology of this illness is not well defined and there are no known structural abnormalities, biomedical markers, nor inflammatory causes to explain the symptoms. There are a number of serious illnesses, such as colon cancer, ulcerative colitis, and celiac disease that mimic IBS. If the Rome III criteria are satisfied and there are no alarm features of more serious illness, an in-depth workup is not necessary. There are numerous treatment regimens for IBS, none of which are curative nor offer universal relief. Some of the treatment regimens, such as antispasmodics and antidiarrheals, are not suitable for aviators because of anticholinergic effects and sedation. The aeromedical disposition decision is always challenging because of the vagaries of this illness. In general, a more liberal policy for pilots in civil aviation would be in order as long as symptoms are not frequent nor severe and not requiring antispasmodics or antidiarrheals while flying. A more conservative policy is in order for military pilots, possibly requiring restriction to multiseat aircraft. PMID- 22097643 TI - Chemical and traumatic occupational eye exposures in aviation personnel. AB - INTRODUCTION: The eye is vulnerable to chemical exposure and foreign body infiltration in the occupational setting. Individuals working in the aviation field are prone to these types of exposures. METHODS: We conducted a 28-mo retrospective chart review to document the number of airline workers complaining of chemical or foreign body exposure to the eye at an onsite airport medical clinic. The International Classification of Diseases, Ninth Revision (ICD-9), code for chemical conjunctivitis (372.5), was used to identify patients' charts. We documented the type of treatment that was initiated and whether there was eye damage. We further investigated the chemical composition of the products and whether there was any associated toxicity. RESULTS: Few instances of chemical exposure and foreign body infiltration were found. Patients were exposed to the following products: lubricants (e.g., naphthenic oils), hydraulic fluid (e.g., petroleum or phosphate ester based), jet fuel (e.g., kerosene), and de-icing agents (e.g., propylene glycol). There was no documentation regarding the use of personal protection equipment in the patients' charts. All patients received eye irrigation with normal saline. No sequelae were documented. CONCLUSION: Airline personnel are exposed to a variety of chemical agents in the workplace. None of the agents that workers were exposed to in this small study exhibited toxic effects to the eye. Proper use of personal protection equipment in aviation personnel may limit the number of chemical and foreign body eye exposures. PMID- 22097645 TI - Challenges in aerospace medicine education. AB - Aerospace medicine training and research represents a dream for many and a challenge for most. In Canada, although some opportunities exist for the pursuit of education and research in the aerospace medicine field, they are limited despite the importance of this field for enabling safe human space exploration. In this commentary, we aim to identify some of the challenges facing individuals wishing to get involved in the field as well as the causal factors for these challenges. We also explore strategies to mitigate against these. PMID- 22097644 TI - Prostate cancer incidence in U.S. Air Force aviators compared with non-aviators. AB - INTRODUCTION: Several studies investigating whether prostate cancer incidence is elevated in aviators both in the civilian and military sectors have yielded inconsistent findings. Most investigations have compared aviators to the general population. Instead, our study compared prostate cancer incidence rates among officer aviators and non-aviators in the U.S. Air Force (USAF) to reduce confounding by socioeconomic status and frequency of medical exams. METHODS: This retrospective analysis ascertained prostate cancer cases using the Automated Cancer Tumor Registry of the Department of Defense linked to personnel records from the USAF Personnel Center to identify aviators and non-aviators. Survival analysis using the Cox Proportional Hazards model allowed comparison of prostate cancer incidence rates in USAF aviators and non-aviators. RESULTS: After adjustment for age and race, the hazards ratio for prostate cancer incidence comparing aviators with non-aviators was 1.15 (95% confidence interval, 0.85 1.44). Neither prostate cancer incidence nor time to diagnosis differed significantly between the two groups. CONCLUSION: Our study compared prostate cancer rates in aviators with a reference group of non-aviators similar in socio economic level and frequency of exams. When compared to this internal reference group the risk of prostate cancer in USAF officer aviators appeared similar with no significant excess. PMID- 22097646 TI - Medical policy development for human spaceflight at NASA: an evolution. AB - Codification of medical policy for the National Aeronautics and Space Administration (NASA) did not occur until 1977. Policy development was based on NASA's human spaceflight efforts from 1958, and the need to support the operational aspects of the upcoming Space Shuttle Program as well as other future activities. In 1958, the Space Task Group (STG), a part of the National Advisory Committee on Aeronautics (NACA), became the focal point for astronaut selection, medical support, and instrumentation development in support of Project Mercury. NACA transitioned into NASA in 1958. The STG moved to Houston, TX, in 1961 and became the Manned Spacecraft Center. During these early years, medical support for astronaut selection and healthcare was provided through arrangements with the U.S. military, specifically the United States Air Force, which had the largest group of subject matter experts in aerospace medicine. Through most of the 1960s, the military worked very closely with NASA in developing the foundations of bioastronautics and space medicine. This work was complemented by select individuals from outside the government. From 1958 to 1977, there was no standard approach to medical policy formulation within NASA. During this time, it was individualized and subjected to political pressures. This manuscript documents the evolution of medical policy in the NASA, and provides a historical account of the individuals, processes, and needs to develop policy. PMID- 22097647 TI - Two-depth transcranial Doppler: a novel approach for non-invasive absolute intracranial pressure measurement. PMID- 22097648 TI - You're the flight surgeon: aortic insufficiency. PMID- 22097650 TI - [After almost half a century...it is now]. PMID- 22097649 TI - This month in aerospace medicine history. PMID- 22097651 TI - [Conservative treatment of the pectus carinatum]. AB - INTRODUCTION: Pectus carinatum (PC) is a deformity that involves the protrusion of the anterior chest wall. It is 10 times less frequent than pectus excavatum. It has a progressive growth and is more common with men. There are two different types, the lower or condrocorporal which is the most common one, and the upper or condromanubrial. Most of the time there are no cardio-respiratory symptoms. OBJECTIVE: We present our experience in the orthopedic treatment of the pectus carinatum. METHOD: Retrospective review of patients treated in our hospital from 2002 until 2009. Patients were treated with observation, aerobic exercises, postural change and/or compression braces. Literature review was performed of the treatment for this pathology. RESULTS: 18 patients have been diagnosed with PC, 16 were men and 2 women. All were treated in a nonoperative way. Only 11 of them used a compression brace. We missed two follow-ups and another has just yet begun to achieve proper results. All the rest have had excellent results with nonoperative treatment. None of them have had a surgical treatment. CONCLUSION: The PC is a disease that most often is a cosmetic problem, with no impact on a cardio-respiratory level. Classically it has been a surgical entity. In our experience we have found that the orthopedic method is an effective alternative, safe and with a significant reduction in morbidity. But we need the collaboration of the patient to accept and maintain continuity in the use of the prostheses. PMID- 22097652 TI - [Noninvasive positive pressure ventilation in postoperative period of tracheal surgery]. AB - OBJECTIVES: Reconstructive surgery of the airway often means prolonged periods of intubation during the post-operatory period, increasing the needs for drugs and favoring the appearance of infectious complications. We present an original system of ventilatory support with non-invasive positive pressure ventilation (NIPPV) using in patients subjected to reconstructive surgery of the airway. PATIENTS AND METHODS: A retrospective study in patients undergoing reconstructive procedures of the airway in the year 2009 was carried out. We exclude those treated endoscopically and those who had vascular rings. The positive pressure mechanism used in the Surgery Critical Care Unit was a design made by the unit based on the circuit devised by Mapleson that provides optimum levels of ventilation without need for connection to a respiratory. We analyze the results, postoperatory intubation time, time dependent on NIPPV and medical treatment received. RESULTS: A total of 7 patients (1 Female and 6 Males) with median age of 1.6 (0.1-7.5) years were included. The diagnoses were: 4 subglottic stenosis, 2 had tracheal stenosis and 1 subcarinal stenosis with involvement of both principal bronchioles. The techniques used were: laryngotracheoplasty with costal cartilage graft (4), tracheoplasty with costal cartilage (1) and sliding tracheoplasty (2) with bilateral bronchoplasty in one of them. The mean time of nasotracheal intubation was 3 days, and mean time of NIPPV was 2.3. No patient required reintubation and none had infectious complications. CONCLUSIONS: Ventilatory support by VPPNI allows effective extubation in these patients, it being possible to maintain a safe airway. Infectious complications, frequent in prolonged intubations, were not observed in any of the cases. PMID- 22097653 TI - [First results of the orchiopexy via scrotal approach]. AB - PURPOSE: We present our first results with the technique described by Bianchi and Squire in 1989 for the surgical treatment of undescended testis by scrotal incision as an alternative to the traditional inguinal approach. MATERIALS AND METHODS: Prospective study of patients operated with the diagnosis of cryptorchidism with scrotal orchidopexy from October 2008 through July 2009. INCLUSION CRITERIA: patients with inguinal palpable testis, scrotal orchidopexy, testicular position was assessed at 6 months and/or one year after surgery. All procedures were performed by the same surgeon. Retractile testes were excluded. We studied the preoperative localization of the testis, the average surgical time, presence or absence of the processus vaginalis, conversions to the traditional inguinal orchiopexy, complications and location of six months and one year after surgery. RESULTS: A total of 50 orchidopexy were performed in 39 patients during this period. Aged between 1 and 12 years (mean 5 years, median 4 years). Were located in the intraoperative exam under anesthesia, fifteen testes in the inguinal canal and 35 in the external inguinal ring. Operative times ranged from 15 to 60 minutes (mean 34 minutes). The processus vaginalis was patent in 25 procedures (50%) and were ligated via the scrotal incision. Two patients required conversion to a traditional inguinal approach. All testes were satisfactorily positioned in the scrotum and there were no cases de testicular atrophy or ascent, hernia o hydrocele formation with followup that ranged from 6 months to 1 year. CONCLUSIONS: The technique of orchiopexy with scrotal approach is a safe, well tolerated and reliable method. PMID- 22097654 TI - [Evaluation of the anal position in newborns and children with chronic constipation. Incidence of anterior ectopic anus]. AB - INTRODUCTION: Anterior ectopic anus (AEA), continues to be a controversial issue. The objective is to determine the normal position of the anus or anal ano-genital index (AGI) in newborns (NB) and in a group of infants with chronic constipation, know the incidence of AEA in both groups, and its relationship with constipation. METHODS: A prospective aleatory study is performed in where the AGI is determined in 529 NB and 64 older patients with chronic constipation. The AGI is obtained by dividing the distances (cm): vulvar fornix-anus/fornix-coccyx in females and scrotum-anus/scrotum-coccyx in males. The NB group is further studied for gestational age, weight, number of meconium discharges and anal calibration. The newborns with AEA are then controlled to exclude constipation. In patients with chronic constipation, their age, sex and AGI are evaluated. The statistical comparisons are made by a Student's t test and Welch's t test for independent samples. RESULTS: 49.5% of NB are male. The average gestational age is 38.95 +/- 2.08/w in NB females and 38.54 +/- 2.26/w in NB males. The average weight is 3101.91 +/- 511.41/g in newborn females and 3145.14 +/- 573.36/g in newborn males. The average AGI of NB females is 0.40 +/- 0.05 and NB males 0.53 +/- 0.06. AEA is considered with AGI < 0.30 in females and < 0.41 in males. 2.2% of NB females (6/267) and 1.1% of NB males (3/262) have AEA. There is a significant difference between the AGI of NB females and NB males (p < 0.0001). 98% of NB discharge meconium in the first 24 hours. 2 NB females with AGI 0,21 and 0,26 had severe constipation in the first months of life. In group with chronic constipation (64 pacients), 59.4% are female. The AGI is 0.36 +/- 0.1 in females and 0.47 +/- 0.1 in males (p < 0.0001). Concerning of AEA in the NB group (AGI < 0.30 in females and 0.41 in males) incidence of AEA in group with chronic constipation is 35% in males and 47% in females. CONCLUSIONS: The position of the anus in the perineal floor is anterior in females, with significant differences (p < 0.0001) to the AGI in males. AEA has more incidence in females (2.2%). In the constipated group 47% of females had AEA and it is considered the probable reason for this disorder in these patients. To conclude, each NB evaluation protocol should include determination of the AGI in the neonatal period to exclude AEA and to prevent clinical consequences. PMID- 22097655 TI - [Robotic surgery: first pediatric series in Spain]. AB - OBJECTIVES: Despite several surgical robots operating in Spain, the experience in pediatric pathology is limited. We found interesting to review the first full pediatric series in our country. We would like to share as well our views on the transition from conventional to robotic laparoscopy. METHODS: Retrospective review of all the pediatric laparoscopic surgery assisted by the da Vinci robot (Intuitive Surgical), in our center, between April 2009 and February 2010. RESULTS: 8 patients were operated (7-15 years), with an average weight of 42 Kg (18 to 83 Kg). 11 procedures were performed: bilateral salpingo-oophorectomy (1), inguinal hernia (1), cholecystectomy (4), splenectomy (2), resection of pancreatic mass (1), fundoplication (1), adrenalectomy (1). All proceedings, except two, were completed with the robot. As complications, there was one intraoperative bleeding that required blood transfusion, and in the postoperative period, there was a surgical wound infection. There were no conversions to open surgery. The average time of preparation before surgery was 130 minutes. The three-dimensional vision and lack of tremor are the main advantages cited by all surgeons. CONCLUSIONS: The learning curve of Robotic Surgery is shorter than that of conventional laparoscopy. Trained surgeons can perform complex procedures laparoscopically from the outset. The main difficulty in children is the proper planning of trocar placement, due to the smaller size of the surgical field. The organization of surgery is complex and success depends on close collaboration of all stakeholders. PMID- 22097656 TI - [Gastroesophageal reflux disease. Evaluation and indication for surgical treatment by esophageal phmetry]. AB - INTRODUCTION: Oesophageal pH monitoring is considered the best procedure to assess the severity of gastroesophageal reflux disease (GERD), conditioning its treatment. The indication for surgery is becoming less common. We intend to meet this test to what extent it has influenced. MATERIAL AND METHODS: We recruit patients treated in our Centre since the introduction of pH monitoring. We compare the number of times before and after its use. We value clinical manifestations, usual pH metric values versus non-operated patients with pathological test, associated pathology. RESULTS: SAMPLE: 91 patients, 151 pH metric studies (98 preoperative). Number of interventions prior to introduction of pH monitoring: 20/year, post: 3.79/year. SYMPTOMS: gastrointestinal 60.2%, respiratory 10.2%, mixed 24.5%. 495 non-operated patients, 692 pathological studies. PH metric values operated/not operated: No. reflux 116.91 +/- 125.46/101.69 +/- 83.39 (p < 0.001), No. reflux >5 minutes 8.49 +/- 8.28/4.43 +/- 4.85 (p = 0.001), longest reflux 60.21 +/- 95.93/31.16 +/- 80.09 (p < 0.001), clearance 1.27 +/- 1.44/0.86 +/- 1.05 (p = 0.04), DeMeester 52.74 +/- 56.21/29.49 +/- 23.57 (p < 0.001). 14 of 98 preoperative pH monitoring were normal. Associated pathology operated/not operated: 13.26%/ 7.47%. CONCLUSIONS: The pH metric control of patients with GERD and the progress of medical treatment have led to a decrease in surgical procedures. In our experience, the intensity of GERD is a valuable parameter in deciding on the surgery. We attach particular value parameters measuring oesophageal clearance and indices that integrate several of them. However, in some patients without pathological pH monitoring, we have indicated the operation. The prevalence of associated pathology in the operated makes us value them more demanding. PMID- 22097657 TI - [Laparoscopic appendectomy with endoloop: results of our experience]. AB - There are several different techniques for laparoscopic appendectomy (LA), with different material requirements and approach. We present the results from our series, where we employ monopolar hook for mesoappendix dissection and double polyglactin endoloop for ligation of appendicular stump. The appendix is taken out through the Hasson trocar without any contact with abdominal wall, in a completely laparoscopic procedure. We sought to analyze the security of this technique. We reviewed retrospectively every LA for acute appendicitis performed during the last 10 years in our Hospital. We collected data regarding surgical procedure and postoperative outcome, focusing on intraoperative or postoperative complications. A total of hundred and ten (110) LA for acute appendicitis (from simple appendicitis to perforated appendicitis) were performed. Mean operative time was 74.7 minutes (median 70 min, SD 24.43 min, min. 25, max. 130 min). Ten patients (9.09%) had postoperative complications, consisting in intraabdominal abscess in 6 patients (5.4%) and wound infection in 3 patients (2.7%). No major complication was found, as uncontrolled hemorrhage, bowel perforation or stump dehiscence. No patient needed a second surgical procedure in the postoperative time. Laparoscopic appendectomy with polyglactin endoloops is a completely laparoscopic and safe procedure, without any intraoperative complication in our series. Laparoscopic approach with 12 mm Hasson trocar and two 5 mm working trocars allows a nice aesthetic result. PMID- 22097659 TI - [When is it best to perform enterostomy closure in premature infants with necrotizing enterocolitis?]. AB - INTRODUCION AND AIM: The enterostomy used in the treatment of Necrotizing Enterocolitis (NEC) causes many complications before and after its closure. The aim of this study was to examine the complications of closure aiming at determining the best timing for this operation. PATIENTS AND METHOD: Retrospective review patients (p) below 1500 g with NEC in whom the enterostomy was closed in the last seven years. P were divided into two groups: PC (planned closure after uncomplicated postoperative period) and CC (advanced closure due to stomal--excessive looses--or to parenteral nutrition complications--septicemia, liver dysfunction-). We compared the age at closure, time of enterostomy, weight gain and complications. RESULTS: Out of a total of 25 p requiring surgical treatment for NEC, 16 from the PC group and 9 from the CC group were included. The mean age at the moment of the closure were, respectively, 129 + 65 vs. 204 +/ 121 days (p < 0.05). Weight at closure was 2665 +/- 841 vs. 4665 +/- 2076 g (p < 0.05); the mean time with the enterostomy was 105 +/- 64 vs. 187 +/- 116 d (p < 0.05), and the weight gain was 1779 +/- 859 vs. 3693 +/- 2155 g (p < 0.05). After stomal closure, 7/16 p of the CC group (43%) and 2/9 of the PC group (22%) required reoperation due to severe complications (ns). In 4 of them, three of the CC group and one of the PC group, a new enterostomy was performed. CONCLUSIONS: In p with enterostomy-related complications, closure has often to be advanced and it is performed in deficient nutritional conditions. Severe complications after enterostomy closure required reoperation in 43% of the CC group and in 22% of the PC group. Although there was no statistically significant difference, the trend indicates an augmented risk in CC group. The timing for enterostomy closure should be chosen individually. At the time of indicating the closure, the high risk of complications, should be taken into account particularly in preterms with enterostomy-related problems. PMID- 22097658 TI - [Mandibular distraction osteogenesis in patients with craniofacial malformation]. AB - Craniofacial malformations (Pierre-Robin sequence, Treacher-Collins syndrome, Nager syndrome, etc.) are frequently associated to severe mandibular hypoplasia, which can cause upper airway obstruction by retroposition of the base of the tongue in the posterior pharyngeal space. Most of the patients respond to postural treatment. In prone decubitus position, it may be necessary to monitor oxygen saturation, insert a nasopharyngeal tube and even an endotracheal one. In more severe cases with prolonged and frequent pauses of apnea, tracheostomy may be necessary, but it is associated with high morbidity and sometimes mortality. In the last two years, in the Multidisciplinary Cleft Lip and Palate Unit of the Hospital Virgen de las Nieves, 4 children with severe obstructive apnea secondary to severe mandibular hypoplasia have been treated with mandibular distraction osteogenesis, this procedure being effective in the resolution of the condition. It has avoided tracheostomy, it has lengthened the jaw in a period of 2-3 weeks. During this time, the obstructive respiratory problems and also swallowing problems have disappeared. The esthetic results were excellent and the complications, for the moment, minimum. PMID- 22097661 TI - [Laparoscopy as diagnostic-therapeutic method in abdominal traumatism in the pediatric age]. AB - The management of blunt abdominal traumatism with a moderate amount of free peritoneal fluid and without solid organ injury as well as the one of minimal penetrating trauma is controversial. We present three cases of blunt abdominal trauma and two of penetrating trauma that underwent diagnostic laparoscopy in our department. We found a small bowel perforation in one of the cases of blunt trauma that was repaired by externalization of the jejuna loop by one of the ports. In the other two cases we found intestinal and mesenteric contusions and free fluid that were treated by peritoneal drainage. One of the cases of penetrating trauma presented omentum evisceration with no other injuries and the second presented a gastric perforation that needed reconversion to laparotomy. In our experience and according to literature, laparoscopy should be taken into account as a diagnostic procedure and sometimes also therapeutic in selected cases of both blunt and penetrating abdominal trauma in pediatric population. PMID- 22097660 TI - [Management of pediatric iatrogenic tracheobronchial lesions in pediatric patients]. AB - AIM: To present our experience in the management of three cases of tracheobronchial iatrogenic injuries and the literature revision about this pathology. MATERIAL AND METHODS: We present 3 patients treated in our center with tracehobronchial iatrogenic injuries since 2005. RESULTS: Case 1. 8 year old boy who present cervical, mediastinal and facial emphysema after foreign body extraction. After 9 days of conservative management without endotracheal intubation all emphysema remited, and the bronchial injury healed. Case 2. 1 month old toddler who presented after cardiovascular surgery and endotracheal tube extraction dyspnea and hypoxia. Fibrobronchoscopy showed subglotic posterior tracheal disrupture. Fifteen-day endotracheal intubation throughout the injury was enough management on this patient. One month later the tracheal injury was completely healed. Case 3. 5 year old girl with tracheobronchial iatrogenic injury after orotracheal intubation who developed neumothorax and subcutaneous emphysema. After fiteen-day conservative management without intubation the injury healed. CONCLUSION: After iatrogenic tracheobronchial injury suspicion there were confirmed by fibrobronchoscopy. Conservative treatment in this patients was successful. Orotracheal intubation prevented air leaking through the tracheal injury allowing complete healing of the trachea. Bronchial injuries healed without needing intubation or mechanical ventilation. Articles reviewed recommend surgical treatment in those cases who had complete or large airway disrupture or in those who were misdiagnosed. PMID- 22097663 TI - [Sudden abdominal pain...is it a surprise? Necrosis of an ectopic spleen]. AB - An ectopic/wandering spleen is rare in children. It results from the absence or laxity of the supporting ligaments which may cause torsion of the splenic pedicle with subsequent infarction. We present a case of a six-year-old girl, with history of onphalocele, dextrocardia and ectopic spleen (incidentally discovered three years ago as an abdominal mass on physical examination), with acute abdominal pain and signs of peritoneal irritation. Sonography showed an enlarged ectopic spleen in the pelvis. Computed tomography scan did not enable visualization of the spleen and allowed the identification of a pelvic mass without uptake of intravenous contrast. Splenectomy was performed due to splenic infarction. In the presence of a wandering spleen, even if asymptomatic, splenopexy may be performed to minimize complications, and together with acute abdominal pain, torsion of splenic pedicle may be considered. PMID- 22097662 TI - [Odontogenic myxoma of nasosinusal localization in a pediatric patient]. AB - In the present study we report and discuss a case of odontogenic myxoma in a 13 month-old patient. Only two other reports have been published in the literature describing the occurrence of this type of tumor at an earlier age. Odontogenic myxoma is a benign mesenchymal neoplasm of the maxilla more common between the third and fourth decades of life. The case here reported is exceptional as it presents in an infant and, although some cases have been reported in the literature, this type of tumor is rare in early childhood. The most common locations include the ascending ramus and the angle of the jaw, although these tumors may also affect the upper maxilla, in which case they may involve the maxillary sinus. According to the review of the literature, these tumors show a recurrence rate of about 25%. Consequently, after the intraoperative clinical examination of the lesion and the assessment of the initial suspected diagnosis by means of intraoperative biopsy under general anesthesia, we carried out the resection of the tumor with wide margins at some points of the tumor location. PMID- 22097664 TI - [The Pediatric Surgical Service exists in Sabadell from 1968]. PMID- 22097665 TI - Sixtieth anniversary--West Indian Medical Journal. PMID- 22097666 TI - The West Indian Medical Journal and the non-communicable diseases (NCDs) the next 60 years. PMID- 22097667 TI - The road to the United Nations High Level Meeting on chronic non-communicable diseases. AB - The United Nations High Level Meeting (UNHLM) on non-communicable diseases (NCDs) will take place in New York on September 19 and 20, 2011. This historic event will focus world attention on the chronic non-communicable diseases (CNCDs) for the first time. In 2008, CNCDs, principally cardiovascular disease, cancer; chronic lung diseases and diabetes, accounted for 63% (or 36 million) of the 57 million deaths occurring worldwide. Many of these deaths may be considered premature (involving 9.1 million persons aged less than 60 years), and around 80% of overall deaths occurred in low and middle income countries. Chronic non communicable diseases are therefore a major cause of premature death, with resulting enormous negative impact on national economies and global development, while continuing to increase at worrying rates particularly in the developing world. Without successful interventions, NCD-related deaths are projected to reach 52 million by 2030. PMID- 22097668 TI - From Port-of-Spain summit to United Nations High Level Meeting CARICOM and the global non-communicable disease agenda. AB - The English-speaking Caribbean has the highest per capita burden of chronic non communicable diseases (CNCDs) in the region of the Americas. Building on a long history of cooperation in health among the Caribbean Community (CARICOM) and past successes in eliminating/reducing communicable diseases through collective action, non-communicable diseases (NCDs) have now been targeted CARICOM convened a "first-in-the-world" summit of Heads of Government to address NCDs, which generated the Port-of-Spain NCD Summit Declaration, "Uniting to Stop The Epidemic of Chronic Noncommunicable Diseases". This 15-point declaration calls on all of government, civil society and the private sector to jointly tackle the common risk factors for the major chronic diseases, and improve the care of such diseases. Implementation of this declaration has been mixed, being most successful where there were regional supports, and in countries with populations > 250 000 reflecting country capacity. CARICOM has elevated this approach to the global level through successful advocacy for a United Nations High Level Meeting on NCDs to be convened in September 2011. Jamaica will be one of two co facilitators of this meeting, a reflection of the role of CARICOM countries in advancing the NCD agenda at the global level. CARICOM Heads of Government should attend this meeting, showcase the implementation of the NCD Summit Declaration in the Caribbean, commit to enhancing systems and resources, endorse and implement the commitments made and identify and support leadership for sustained action and accountability for these initiatives. PMID- 22097669 TI - Chronic non-communicable diseases and the economy. AB - There is no question that chronic non-communicable diseases (CNCDs) pose the single, greatest sustained threat to the stability of health systems worldwide. While undoubtedly the main dimension of the CNCDs challenge is in respect of the health and well-being of the population, it is becoming increasingly obvious that CNCDs are also posing a serious challenge to economies. Health system costs are increasing faster than national income in almost all nations and the main cause is the growing incidence of CNCDs and the diverse spill-over effects. The concern is that if this continues, there will come a time when the economic system will simply no longer be capable of coping with the burden of the CNCDs. In these circumstances the economist has two major concerns. The first is to understand and explain how CNCDs affect the functioning of the economic system. It is argued that while the analysis will necessarily begin on the qualitative level, for policy purposes it must also be taken to the quantitative level. The second major concern of the economist is to understand and explain how the working of the economy influences the incidence of CNCDs in particular countries. The author suggests that at a time when the prevention and management of CNCDs are high on the agenda of many nations, it is important to know whether the measures being taken to improve human development and economic well-being are themselves contributing to an increasing incidence of CNCDs particularly in small, vulnerable, open economies. In this regard, this paper briefly explains how CNCDs affect the economic system and presents some of the estimates of quantitative impact on the economy. PMID- 22097670 TI - Chronic disease in the Caribbean: strategies to respond to the public health challenge in the region. What can we learn from Jamaica's experience? AB - With the advent of the epidemiological transition, chronic non-communicable diseases (CNCDs) have emerged as the leading cause of death globally. In this paper we present an overview of the burden of CNCDs in the Caribbean region and use Jamaica as a case-study to review the impact of policy initiatives and interventions implemented in response to the CNCD epidemic. The findings show that while Jamaica has implemented several policy initiatives aimed at stemming the tide of the CNCD epidemic, a comparison of data from two national health and lifestyle surveys conducted in Jamaica in 2000/01 and 2007/08 revealed that there was an increase in the prevalence of intermediate CNCD risk factors such as hypertension and obesity. We therefore present recommended strategies which we believe will enhance the current CNCD response and thus reduce, or at least stem, the current epidemic of CNCDs. PMID- 22097671 TI - Taming the burgeoning stroke epidemic in Africa: stroke quadrangle to the rescue. AB - OBJECTIVES: Globally, stroke is the second leading cause of death. This is a systematic review of the existing literature to examine the burden and profile of stroke in the World Health Organization (WHO) African region and proffer coordinated and responsive means to tackle the epidemic. METHODS: A systematic review of the literature was conducted according to the Centre for Reviews and Dissemination Guidelines using Pubmed, African Journals On-Line and Google Scholar databases. Over 1300 articles were obtained. All abstracts were screened, and every article that might have contained relevant information was read in full. Their heterogeneity made meta-analysis impossible. So a critical assessment of the data with a narrative review was conducted. RESULTS: Stroke has an annual incidence rate of up to 316 per 100 000, a prevalence rate of up to 315 per 100 000 and a three-year fatality of up to 84% in Africa. In 2002, model-based estimated age-adjusted stroke mortality rates ranged between 168 and 179 per 100 000 population for countries in the African region. There is severe scarcity of facilities and human resources for prevention, investigations, acute care and rehabilitation of stroke patients in Africa. CONCLUSIONS: Africa bears a heavy burden of stroke. This author proposes a stroke quadrangle comprising a concerted network of four pillars: demographic surveillance and stroke research network, integrated community-based primary and secondary prevention programmes, easily accessible and well-equipped acute stroke care services, and neuro-rehabilitation centres and services. This network could be reinforced using information and communication technologies, telemedicine facilities and linked health information systems. PMID- 22097672 TI - An update on the burden of cardiovascular disease risk factors in Jamaica: findings from the Jamaica Health and Lifestyle Survey 2007-2008. AB - BACKGROUND: Previous studies have documented a high burden of cardiovascular disease (CVD) risk factors in Jamaica and suggest that mortality from CVD may be increasing. This paper provides an update on the burden of CVD risk factors in Jamaica using data from the most recent national health survey and evaluates the impact of obesity and physical activity on other CVD risk factors. METHODS: The Jamaica Health and Lifestyle Survey 2007-2008 (JHLS-2) recruited a nationally representative sample of 2848 Jamaicans, 15-74 years old between November 2007 and March 2008. An interviewer administered questionnaire was used to obtain data on demographic characteristics, medical history and health behaviour Blood pressure and anthropometric measurements were made using standardized protocols and capillary blood samples were obtained to measure fasting glucose and total cholesterol. Prevalence estimates for the various CVD risk factors were obtained within and across sex and other demographic categories. Data were weighted for the complex survey design, nonresponse to questionnaire items or failure to complete some segments of the evaluation. RESULTS: Prevalence estimates for traditional CVD risk factors were: hypertension, 25%; diabetes, 8%; hypercholesterolaemia, 12%; obesity, 25%; smoking 15%. In addition, 35% of Jamaicans had prehypertension, 3% had impaired fasting glucose and 27% were overweight. A higher proportion of women had diabetes, obesity and hypercholesterolaemia while the prevalence of prehypertension and cigarette smoking was higher in men. Approximately 50% of persons with hypertension, 25% of persons with diabetes and 86% of persons with hypercholesterolaemia were unaware of their risk status. In multivariate analysis, obesity was associated with increased odds of hypertension, diabetes and hypercholesterolaemia while physical inactivity was associated with higher odds of diabetes. CONCLUSION: The burden of CVD risk factors in Jamaica remains very high and warrants interventions to reduce CVD risk. PMID- 22097673 TI - Prehypertension in Jamaica: a review of data from recent studies. AB - Prehypertension is defined as a systolic blood pressure of 120-139 mmHg or diastolic blood pressure of 80-89 mmHg in patients not on medication for hypertension. Recent studies have shown that prehypertension has a high prevalence in both western and eastern countries and is associated with cardiovascular disease (CVD) risk factors, incident CVD and CVD mortality. We reviewed data from ongoing epidemiological studies in Jamaica in order to provide an update on the prevalence and predictors of prehypertension in Jamaica. Studies included were the Jamaica Health and Lifestyle Surveys (2000-2001 and 2007-2008), the Jamaica Youth Risk and Resiliency Behaviour Survey 2006, the 1986 Jamaica Birth Cohort Study and the Spanish Town Cohort Study. The prevalence of prehypertension in the most recent national survey was 35% (95% CI 33, 38%). Prevalence was higher in men compared to women (42% versus 29%). Jamaicans with prehypertension were more likely to have other CVD risk factors and were three times more likely to develop hypertension compared with persons with a normal blood pressure. Prevalence was also high among youth, particularly males. Longitudinal analysis from the 1986 birth cohort suggested that prehypertension may be more common in persons with low birthweight or short birth length. Physicians and public health practitioners should recognize the increased CVD risk associated with prehypertension and should begin to institute CVD prevention measures in persons with prehypertension. Sex differences and the early onset of prehypertension in men require further exploration. PMID- 22097674 TI - The socio-economic determinants of obesity in adults in the Bahamas. AB - OBJECTIVE: To determine the socio-economic determinants of obesity in adults in The Bahamas. DESIGN AND METHODS: A subpopulation of adults 21 to 60 years was analysed for socio-economic differences in obesity levels. Data from the 2001 Bahamas Living Conditions Survey, a nationwide comprehensive household survey which included anthropometric measurements, were used. Bivariate and binary logistic regression methods for complex samples were employed. FINDINGS: Overall obesity prevalence was 32% (38% female, 25% male, p = < 0.0001). An inverse relationship by education appeared to be the strongest predictor for all persons (OR = 0.78, CI 0.67, 0.90; p < 0.0001). This relationship was also evident for females (OR = 0.71, CI 0.59, 0.85; p < 0.0001) while a positive relationship existed by economic level for males (OR = 1.23, CI 1.07, 1.41; p = 0.005). There was a difference in food group expenditure for starchy vegetables only (p = 0.049). Other food group household expenditure, urban residence and female headed households showed no significant differences by obesity. CONCLUSIONS: In line with international trends, obesity rates are high in The Bahamas, and especially affect females of lower socio-economic status. Public policy that targets this group is necessary to address this health concern. PMID- 22097675 TI - Childhood obesity in the Caribbean. AB - OBJECTIVE: To determine the prevalence of overweight among school children in Bonaire, an island in the Caribbean, and to obtain clues for prevention of overweight. METHODS: In a cross-sectional school-based study, weight and height were measured in all 4-16-year old children in Bonaire (n = 2148). Body mass index was categorized as defined by the International Obesity Task Force (IOTF). The children were administered a questionnaire pertaining to lifestyle and nutrition. RESULTS: The prevalence of overweight, including obesity, in boys is 24.3%, and 31.9% in girls; obesity is 9.9% and 13.7%, respectively. Approximately half of the children have an unhealthy food pattern. Significantly less overweight (49%) and obese children (45%) are physically active for > 1 hour/day compared to normal weight children (56%). CONCLUSION: The prevalence of overweight and obesity in children in Bonaire is high. Prevention of overweight should focus on stimulating healthy eating habits and more physical activity. PMID- 22097676 TI - Obesity prevention: the key to non-communicable disease control. AB - Non-communicable diseases (NCDs) are the main public health problem in the Caribbean and they place a severe economic burden on the health systems in the region. This paper contends that preventing obesity is a critical factor in controlling NCDs. The paper further argues that obesity prevention is more likely to come from structural and policy-related changes to the environment than from medical interventions targeted at the individual. Rolling back the rapid increase in obesity in the Caribbean requires much more than the traditional passive approach that relied almost entirely on education for individual behavioural change. The traditional models of obesity control have generally failed globally and a new public policy approach needs to be instituted to attack this epidemic in a multisectoral way. Effective control of obesity will require a shift away from the traditional focus on clinical management and individual behaviour change towards strategies which deal with the environment in which such behaviours occur Outlined in this paper are key policy changes required by the various sectors whose inputs are vital to the success of prevention efforts. PMID- 22097677 TI - Chronic non-communicable disease risk factor survey 2010 among University of the West Indies staff at Cave Hill, Barbados. AB - OBJECTIVE: To determine the prevalence of risk factors for chronic non communicable diseases (CNCDs) among staff of The University of the West Indies (UWI), Cave Hill campus, in Barbados. METHODS: A self-administered questionnaire comprising validated questions from the WHO STEPS NCD Risk Factor Survey, the Jamaica Healthy Lifestyle (JHL) Survey and the Behaviour Risk Factor (BRF) Survey, was conducted during the Staff Health Day in May 2010, and at four locations on campus during July 2010. Standardized measurements of weight, height and blood pressure were taken. Data were analysed using EXCEL and STATA and results were compared to the Barbados 2007 STEPS NCD survey. RESULTS: The target population was all staff at the Cave Hill campus of UWI. The coverage rate was 25.2% (269/1068); 63.8% of males and 75% of females were either overweight or obese. Ninety-seven per cent ate less than the recommended 5 fruits and vegetables per day. Low levels of physical activity were reported in 51.9% of males and 62.2% of females. Thirty-two per cent of males and 13% of females were binge drinkers. All participants had at least one of the risk factors (current daily smoker < 5 fruits and vegetables/day, physical inactivity, overweight/obese and raised blood pressure) whilst 48% of males and 57.2% of females demonstrated three or more risk factors. These results are similar to those found in the Barbados STEPS NCD risk factor survey of 2007. CONCLUSION: The results confirm a similar high prevalence of NCD risk factors among Cave Hill UWI staff as among the Barbadian population. The study reveals opportunities to inform policy on strategies to positively impact the risk factors. PMID- 22097678 TI - Glaucoma in the English-speaking Caribbean. AB - The Barbados Eye Studies have provided the most comprehensive information on the major eye diseases in African origin populations to date. Black Barbadians have among the highest rates of primary open-angle glaucoma (OAG) reported to date in a population-based study (7.0%). Incidence rates of OAG over a nine-year follow up period were 0.5% per year, and two to five times higher than reported in predominantly Caucasian populations. Risk factors for OAG included older age, male gender higher intraocular pressure, positive glaucoma family history, in addition to lean body mass and a positive cataract history. Low blood pressure to intraocular pressure relationships were also found to increase OAG risk, suggesting an aetiologic role for low vascular perfusion of the optic nerve. Recent analyses revealed a region on chromosome 2 associated with increased OAG risk, which has potential implications for early diagnosis and treatment. Approximately 50% of Barbadians with OAG were unaware of having the disease in the baseline study and this situation remained unchanged nine years later open angle glaucoma causes painless, irreversible loss of vision and there are clear reasons why screening may be of particular public health importance in high risk African descent populations, given the benefits of early detection and appropriate treatment. There are data that suggest that it would be cost effective to conduct open-angle glaucoma screening in Barbados and this has implications for policy and care, with the ultimate aim of reducing glaucoma related blindness. PMID- 22097679 TI - Chronic kidney disease in the Caribbean. AB - Globally, diabetes mellitus and hypertension are major causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Reports from the Caribbean renal registry have also identified diabetes mellitus and hypertension as the leading causes of chronic kidney disease and end-stage renal failure. Chronic non communicable diseases including chronic kidney disease continue to be a major financial challenge in the Caribbean. Patients with chronic kidney disease have high rates of healthcare utilization, morbidity and mortality, and hence constitute a significant economic and clinical burden to the healthcare system. Emphasis should be placed on ways to reduce the incidence of kidney disease and the progression to dialysis. The most economically feasible form of renal replacement therapy that offers the best quality of life should be sought. PMID- 22097682 TI - Integrating mental health into primary care an integrative collaborative primary care model--the Jamaican experience. AB - Many low-income countries face enormous constraints which limit the development of mental health services. The World Health Organization (WHO) made ten recommendations to facilitate the development of mental health services; among these is the integration of mental health into primary care. Jamaica developed an integrated collaborative system of mental health care through the adoption of a primary care model which is central to the delivery of mental health care. This model emphasized the integration of mental health into primary care and, in expanding the role of the mental health team, made it more collaborative. Mental health services were mainstreamed into primary care and several strategies facilitated this process. These included the training of staff in primary care, the availability of psychotropic medication in primary care facilities and the provision of mental health beds at the community level. Furthermore, focus was placed on human development and the involvement of consumers in the policy development and service delivery. This has resulted in a reduction in the population of the mental health hospital and expansion in the community mental health services. PMID- 22097681 TI - Is criminal violence a non-communicable disease? Exploring the epidemiology of violence in Jamaica. AB - There is a high level of criminal violence that afflicts the Jamaican society. While it is certainly noncommunicable in the context of medicine and public health, the concepts of social contagion and the well-established fact of the intergenerational transfer of effects of trauma raise questions as to whether or not it is non-communicable in a social sense. Historically, scholars have linked Jamaican criminal violence to three main roots: poverty and urban decay, political patronage, garrisonisation and more recently to a fourth, the growth in transnational organized crime (TOC). Traditionally as well, policymakers have brought the three discrete perspectives of criminology, criminal justice and public health to bear on the problem. This paper applies a conceptual framework derived from a combination of epidemiology and the behavioural sciences to argue that a sustainable resolution to this looming and intractable social problem must take the form of a cocktail of policies that encompasses all three approaches at levels ranging from the community to the international. PMID- 22097680 TI - Chronic disease and ageing in the Caribbean: opportunities knock at the door. AB - Amidst rapid population ageing, the incidence and prevalence of chronic diseases and their sequelae demand reflective and critical looks at the issue and the subsequent development of informed age-sensitive responses. This paper reviews the burden of chronic diseases in the Caribbean, and its relationship to ageing and the demographic transition. Inter-linkages between the social determinants of health, poverty, ageing, and chronic disease are illustrated. Suggestions are made regarding directions to be pursued and the emerging initiative regarding chronic non-communicable diseases being spearheaded at the United Nations by CARICOM countries PMID- 22097683 TI - Tobacco and non-communicable diseases controlling the tobacco epidemic. PMID- 22097685 TI - Ethical issues in healthcare financing. AB - The four goals of good healthcare are to relieve symptoms, cure disease, prolong life and improve quality of life. Access to healthcare has been a perpetual challenge to healthcare providers who must take into account important factors such as equity, efficiency and effectiveness in designing healthcare systems to meet the four goals of good healthcare. The underlying philosophy may designate health as being a basic human right, an investment, a commodity to be bought and sold, a political demand or an expenditure. The design, policies and operational arrangements will usually reflect which of the above philosophies underpin the healthcare system, and consequently, access. Mechanisms for funding include fee for-service, cost sharing (insurance, either private or government sponsored) free-of-fee at point of delivery (payments being made through general taxes, health levies, etc) or cost-recovery. For each of these methods of financial access to healthcare services, there are ethical issues which can compromise the four principles of ethical practices in healthcare, viz beneficence, non maleficence, autonomy and justice. In times of economic recession, providing adequate healthcare will require governments, with support from external agencies, to focus on poverty reduction strategies through provision of preventive services such as immunization and nutrition, delivered at primary care facilities. To maximize the effect of such policies, it will be necessary to integrate policies to fashion an intersectoral approach. PMID- 22097684 TI - Healthcare for the poor and dispossessed: from Alma-Ata to the Millennium Development Goals. AB - Healthcare models which recognize the equity principle have had to confront the challenge of providing healthcare for the poor and dispossessed. Healthcare premised on "human rights" strives to remove/ reduce barriers to access by a complete waiver of all fees in the public sector or various other subsidies to make healthcare more affordable. Social welfare programmes are held hostage to the vagaries of the economy and resource scarcity. The Alma-Ata's primary healthcare is inherently a health development strategy which embraces a wholistic approach to health and wellness. This strategy, by refocussing on the Millennium Development Goals, can therefore accommodate the innovations required to overcome the challenges posed by technological, financial, cultural and geographical factors to provide a better quality of life for all, but moreso for the poor and dispossessed. PMID- 22097686 TI - Critical evaluation of the optimal medical therapy in the cardiac resynchronization therapy candidates--single centre experience. AB - The aim of the present study was to evaluate the optimal medical therapy in the chronic heart failure (CHF) patients referred from the comunity centres and the outpatients cardiology clinics for the cardiac resynchronization therapy with defibrilator (CRTD) to the Department of Cardiology, Na Homolce Hospital with the device implantation between 1st January 2008 and 30st September 2009. METHODS: The optimal medical therapy was analysed retrospectively from the medical records of 179 consecutive CHF patients NYHA class III-IV. Beta-blockers (BB) were used only in 81% subjects referred for CRTD, ACE inhibitors (ACEI) were used only in 68% patients Angiotensin receptor blockers (ARB) were used in 18% subjects. ACEI or ARB were used in 81%, spironolacton was use in 59%. Recommended target DD for BB (carvedilol 25 mg bid) was used only in 13% subjects, recommended target DD for ACEI (enalapril 10 mg bid) was used only in 9.4% patients. RESULTS: In the Department of Cardiology, the optimal medical therapy was changed after CRTD, BB were used in 95% subjects at discharge (p < 0.01) and the number of patients reaching at least of 50% of recommended daily dose (DD) of BB increased (p < 0.05). ACEI were recommended after CRTD in 80% subjects after implantation (p < 0.05), the number of patients reaching at least of 50% of recommended DD for ACEIs increased too (p < 0.05). There was no significant difference in ARB use recomended in the hospital (19% after CRTD - NS). ACEI or ARB were used in 98% patients after the device implanted (p < 0.05) and spironolacton in 77% after CRTD (p < 0.05). CONCLUSIONS: Despite optimal composition of the optimal medical heart failure therapy only small number of CRTD candidates are reaching recommended drug dose. The optimization of the medical therapy in the specialized center lead to significantly higher proportion of CHF using the optimal therapy with the increased dose of BB and ACEI. PMID- 22097687 TI - [Cost of acute heart failure related readmissions]. AB - AIM OF STUDY: To assess direct in-patient cost and length of stay in the intensive care unit (ICU) and the standard cardiology unit in acute heart failure (AHF) readmissions. RESULTS: Out of 1 759 patients hospitalized with acute heart failure, 223 patients were readmitted to Faculty Hospital Brno-Bohunice (Czech Republic) during study period (61.4% male; mean age 71.2 years) with mean total cost CZK 85 120 (Euro 3 095) per length of stay 9.2 days and interventions. Comparing to the first hospitalization of study cohort (223 pts.) the decrease was recorded in mean room rate, length of stay and need of ICU stay (from 48% to 42% pts.), nevertheless ICU stay increased (from 3.7 days to 4.1 days). The growth of mean cost was recorded in both procedures in angiology (the decrease in number of coronary angiography which is cheaper was more remarkable than PCI decrease in readmitted patients) and arrhythmology (including device: pacemaker, ICD, CRT) which made 57.5% of total readmission costs. CONCLUSION: The difference in mean in-patient cost between the first and second hospitalization was 18%. The antiarrhytmic procedures had the most significant impact on total readmission cost and its variability, butwe assume that these procedures will reduce within next readmissions and their impact will weaken as in angiology procedures. PMID- 22097688 TI - [Vaccination against hepatitis B in patients with chronic renal failure--twenty years follow-up]. AB - AIM: The efficacy of vaccination against hepatitis B was evaluated in patients with chronic renal failure from 4 dialysis units in 1988-2010. PATIENTS AND METHODS: Hepatitis B vaccination was started in 1 271 patients with chronic renal failure (606 female, 665 male). Patients received intramuscularly 3 doses of plasma-derived or since 1990, recombinant vaccine at the interval 0, 1 and 2 months for dialysis patients and 0, 1 and 6 months for pre-dialysis patients. Each vaccine contained 40 microg of hepatitis B surface antigen (HBsAg) in 1 002 patients, however only 20 microg HBsAg in 269 patients till 2000. Blood samples were obtained at the beginning of vaccination, 1-2 month after immunization and biannual thereafter. Serum samples were tested using ELISA methods for HBsAg and antibodies against hepatitis B surface and core antigens (anti-HBs, anti-HBc). The patients without protective anti-HBs level and the patients with waning of anti-HBs antibodies were revaccinated. RESULTS: Anti-HBs antibodies after the third vaccine were investigated in 786 patients. Protective anti-HBs levels (> or = 10 IU/l) were proved in 49%, 65% and 74% patients after the third, fourth and fifth vaccine. The waning of protective anti-HBs antibodies was detected in 47% and 68% of patients during 3 and 5 years after vaccination. The new infections with HBsAg positive status were proved in 28 patients, in 27 of them in period 1988-1994. Anti-HBc seroconversion was observed in 10 patients. CONCLUSION: Vaccination considerably reduced hepatitis B incidence in the patients with chronic renal failure during nineties. However still approximately one quarter of patients did not produce protective anti-HBs level after immunization with recombinant vaccine and new form of vaccination against hepatitis B may be considered also in the Czech Republic. PMID- 22097689 TI - [Normal pulmonary circulation pressure values in healthy subjects at rest and during exercise]. AB - The paper is based on the results of an earlier retrospective international WHO study of normal pressure values in the pulmonary circulation and the right heart in 468 healthy individuals. The results of this study suggest that the pulmonary hypertension should be defined by the mean pulmonary artery pressure at rest of > or = 20 mmHg and not > or = 25 mmHg. Pulmonary wedge pressure should be < 12 mmHg. These results have recently been confirmed by the so far largest retrospective international study of normal values published by Kovacs et al and involving 1187 healthy volunteers. However, this study does not include pulmonary wedge pressure values. Normal values ofthe mean pulmonary artery pressure during exercise are determined by age. In healthy individuals younger than 50 years of age, the mean pulmonary artery pressure during exercise increases in parallel with increasing cardiac output. However, the increase in the mean pulmonary artery pressure during exercise is steeper in healthy individuals aged 50 years and over. This results from a sharper increase in the pulmonary wedge pressure caused probably by diastolic dysfunction of the left ventricle in the older population. PMID- 22097690 TI - [Resynchronization therapy for heart failure--still many question marks]. AB - At present, the potential benefit of resynchronization therapy, i.e. an improved quality of life and prolonged survival in patients with heart failure, is not achieved in every patient. The 30% non-response has prompted a search for new criteria predicting patient response to resynchronization treatment. An absence of mechanical dyssynchrony, viability of the myocardium and an inadequate positioning of the intracardiac left ventricular lead probably limit the response to resynchronization therapy. ECG remains essential for the selection of suitable patients. PMID- 22097691 TI - [Diagnostic algorithm of syncope: integrative approach]. AB - Syncope is a symptom, defined as transient loss of consciousness and postural tone with spontaneous and mostly prompt recovery. At first it is necessary to differentiate other non-syncopal transient loss of consciousness and simple falls, where thorough history taking is pivotal. EGSYS and OESIL risk scores seem to be contributional in initial risk stratification, however they are neither widely accepted nor a part of national guidelines. They are part of the European society of cardiology guidelines, though. Next it is essential expert ECG evaluation, thorough physical status examination, supine and standing blood pressure measurement and carotid sinus massage, if not contraindicated. Successively one has to decide if hospitalization or outpatient management is more suitable. Recently it has been shown, that so-called syncope management units (aimed for short-term hospitalization or fast outpatient examination, including vital function monitoring, echocardiography and facile cathlab access) are effective in fast syncope evaluation. Echocardiography, ECG monitoring and head-up tilt test should be a part of complex diagnostic evaluation. If syncope is not clarified by upon stated methods moreover syncope is recurrent, electrophysiological study, ILR implantation or both are justified. Despite of entire health practitioner's effort, more than 1/3 of syncopes remain unexplained. PMID- 22097692 TI - [Treatment of acute exacerbation of the obstructive pulmonary disease with hospitalization at an intensive care unit]. AB - Bronchodilatation is preferably achieved with beta-2-agonists (SABA), salbutamol. Therapy is intensified with anticholinergics (ipratropium bromide monohydrate). A combined preparation may also be used (ipratropium bromide monohydrate and fenoterole hydrobromide). Methylxantines (theophylline) are the second line option. Corticosteroids are administered orally (prednisolone) or intravenously (methylprednisolone or hydrocortisone). Patients who have problems expectorating are administered mucolytics (ambroxol hydrochloride or bromhexine hydrochloride). Some patients are treated with antibiotics. Oxygenotherapy is indicated in patients with hypoxemia. Insufficient treatment effect and progression of respiratory insufficiency warrants application of mechanical or non-invasive ventilation. PMID- 22097693 TI - [The role of central nervous system in etiopathogenesis of peripheral organ diseases]. AB - Current research on the etiopathogenesis of diseases of peripheral organs is primarily focused on the study of processes affecting those organs directly altered by diseases. As a result, therapeutic interventions are focused on the cells of those organs affected by pathological processes. However, pathological processes are not restricted to any "circumscribed" group of cells. Cells of tissue affected by pathological process interact with cells in the surrounding tissues. Moreover, pathologic processes also induce changes in the activity of the neuroendocrine and immune systems, which also affect the progression of pathological processes. The neurobiological view of diseases is based on the assumption that the nervous system processes signals related to pathological processes in peripheral organs and then consequently modulates it via the autonomic, neuroendocrine, and neuroimmune regulations. The aim of this paper is to explain the basis of the neurobiological view of diseases of the peripheral organs, and then discuss possible therapeutic consequences. PMID- 22097694 TI - [Prognostic markers in chronic lymphocytic leukemia]. AB - Chronic lymphocytic leukemia is the most common leukemia type in Western countries. Even incidence of chronic lymphocytic leukemia is high, this disease remained beyond interest for a very long time. However, in the last few years the view of this disease fundamentally changed and due to intensive study, new knowledge especially on pathogenesis, prognostic factors and therapy based on intensive therapeutic procedures were made. Today we know that usage of classical prognostic factors is insufficient for prognosis evaluation in the individuals. However modern (IgVH mutation status, cytogenetic abberations) and new markers (LPL/ADAM29 ratio, microRNA, markers of angiogenesis etc) have potential to distinguish patients in early stages to groups with significantly different prognosis and predict clinical course of the disease. PMID- 22097695 TI - [Diagnosis and treatment of community-acquired pneumonia in adults]. PMID- 22097696 TI - [Benign solitary cecal ulcer]. AB - Solitary benign cecal ulcer is a non-usual finding without characteristic clinical or radiological performance. Because ofits little frequency and its clinical symptoms often suspicious for the presence of severe diseases like are malignancies, acute abdomen or lower gastrointestinal bleeding, this finding is only rarely diagnosed preoperatively. Definitive diagnosis is almost always made pathologically. In this case report we describe clinical, radiological and pathological findings in our patient with difficulties caused by a solitary benign cecal ulcer. PMID- 22097697 TI - [MR-documented remission of pituitary stalk infiltration in patients with Langerhans cell histiocytosis following treatment with 2-chlorodeoxyadenosine]. AB - In adult patients, Langerhans cell histiocytosis (LCH) manifests most frequently with one or more osteolytic lesions or, alternatively, with pulmonary involvement with nodules and cysts or with skin lesions. Infiltration ofthe central nervous system is a rather rare sign of LCH. The LCH cells have an unexplained affinity to hypothalamus and to pituitary stalk and, consequently, central diabetes insipidus is the most frequent clinical sign of brain involvement in LCH. We describe treatment of 2 adult patients with LCH in whom central diabetes insipidus was the first sign of LCH and MR confirmed pituitary stalk infiltration. The first man was diagnosed with diabetes insipidus and pituitary stalk infiltration at 33 years of age. LCH was confirmed 2 years later by histology of verrucous lesions on the skin of perianal area. The disease affected the skin and CNS. The patient was treated with 2-chlorodeoxyadenosine (5 mg/m2 s.c. for 5 consecutive days of a 28-day cycle). No pituitary infiltration was evident on an MR image after the 4th cycle. Residual perianal infiltration was irradiated. The patient has been in complete remission for 44 months following treatment completion, although vasopressin and testosterone substitution is required. The second man was also diagnosed with diabetes insipidus and pituitary stalk infiltration at 33 years of age. Pulmonary involvement was identified with high resolution CT(HRCT) and high CD1a and S-100 positive elements with bronchoalveolar lavage. This patient further had external auditory canal infiltrations causing chronic discharge from the ears. The patient was treated with 2-chlorodeoxyadenosine as above. A follow up MR after the 4th cycle showed reduction in the infiltration diameter from 5.5 to 3.0 mm. Therefore, 2 chlorodeoxyadenosine 5 mg/m2 s.c. was combined with dexamethasone 20 mg p.o. during the 5th and 6th cycle. The MR image after treatment completion showed remission of the pituitary stalk infiltrate. External auditory canal infiltration diminished as did the nodules in pulmonary parenchyma. Nevertheless, vasopressin substitution is still required. The patient has been in complete remission for 8 months from the completion of the treatment. Pituitary stalk infiltration disappeared after the treatment with 2-chlorodeoxyadenosine in 2 patients; after 4 cycles in the first and after 6 cycles (with an addition of dexamethasone during the last 2 cycles) in the second. PMID- 22097698 TI - Timely findings from birth defects surveillance programs. PMID- 22097699 TI - Clinical differentiation of patent foramen ovale and secundum atrial septal defect: a survey of pediatric cardiologists in Dallas, Texas, USA. AB - BACKGROUND: Public health birth defect surveillance registries rely on health care provider diagnosis and definition of congenital anomalies. Major anomalies are likely to have consistent diagnoses across providers; however, definition of some more common, often minor, defects can be problematic. Of particular frustration are the transient neonatal heart findings: patent ductus arteriosus, patent foramen ovale, and pulmonary artery branch stenosis. Under certain circumstances these findings may be considered true anomalies-patent foramen ovale (PFO) as a clinical finding overlaps significantly with atrial septal defect (ASD) of secundum type, the latter being considered a true congenital malformation. Some criteria must be established to separate these conditions in case ascertainment. It is therefore helpful to understand the clinical definitions of patent foramen ovale and secundum atrial septal defect. METHODS: Pediatric cardiologists in the greater Dallas, Texas metropolitan area were surveyed by telephone, fax, and/or email and asked what criteria they use to distinguish a PFO from a secundum ASD. This was an open-ended question. No baseline parameters were suggested or introduced by the interviewer. Pediatric cardiology fellowship training was identified for each physician to examine the hypothesis that graduates of a given program would use the same diagnostic criteria. RESULTS: Responses were obtained from 22 of 23 pediatric cardiologists. Four measurement criteria were identified: size of the opening, presence or absence of a flap of septal tissue, appearance of the defect on echocardiogram and presence/absence/amount of blood shunting across through the opening. Though there was overlap, diagnostic criteria differentiating PFO and secundum ASD varied among pediatric cardiologists. Two fellowship programs were well represented by the respondent population. Eight respondents were trained at Fellowship 1 and 5 at Fellowship 2. Place of fellowship training was not a strong indicator of which diagnostic criteria were used, even when graduates were in practice together. Physicians in private practice were more likely to report objective measurements as bases for their diagnostic decision. CONCLUSIONS: The pronounced variability in clinical definitions will be a problem for birth defect surveillance and research based upon the resultant database. When different physicians use different diagnostic criteria for borderline defects, it is impossible to know whether a defect ascertained and coded with a standard protocol is the same across the population. Since it is unlikely that consistent diagnostic criteria can be put in place, the surveillance program is burdened with compensating for the variability. PMID- 22097700 TI - Should aggregate US Census data be used as a proxy for individual household income in a birth defects registry? AB - BACKGROUND: Birth Defects Registries do not have access to income data and low household income is associated with adverse pregnancy outcomes of stillbirth, preterm birth, and birth defects. We compared 1999 income data from the National Birth Defects Prevention Study (NBDPS) with 2000 Census block group income data for the residence location of these same mothers. METHODS: We geocoded 339 case mothers and 121 control mothers and assessed household income among case and control mothers by using NBDPS and census block group data. Correlation and concordance were assessed between the 2 data sources' household income data. RESULTS: The household income distribution was similar between case and control mothers within each data source. Both case and control mothers in the NBDPS's lowest household income category (<$20,000/year) reported lower income than was documented in their census block group's median household income (p value<0.0001). A weak correlation was identified between NBDPS interview and census block group income data (control mothers, rs=0.53; case mothers, rs=0.32). There was also poor to fair concordance between the 2 data sources (control mothers, kw=0.28; 95% CI=0.19-0.37 and case mothers, kw=0.18; 95% CI=0.13-0.24). CONCLUSION: These findings demonstrate dissimilar household incomes between NBDPS and census block group data. Caution should be used if block-level data is used as a proxy for individual-level household incomes in population-based birth defects surveillance and research. PMID- 22097702 TI - Exploring the environmental and genetic etiologies of congenital heart defects: the Wisconsin Pediatric Cardiac Registry. AB - INTRODUCTION: The Wisconsin Pediatric Cardiac Registry (WPCR) collects information on infants born in the state of Wisconsin with structural congenital heart disease (CHD). METHODS: The WPCR actively ascertains CHD cases in the state of Wisconsin. Cases must be conceived and born in Wisconsin after January 1, 2000. Once ascertained, subjects are approached to participate in genetic sampling and completion of a questionnaire that assesses family history of CHD, maternal health, and environmental exposures before pregnancy and during the first trimester. In 2009, the WPCR underwent a transition to a new database and from a paper questionnaire to a Web-based questionnaire. RESULTS: The WPCR has screened over 5,100 children and has ascertained 4,919 cases of CHD in the state of Wisconsin during the years 2000 to 2009. During this interval, 1,982 completed questionnaires and 1,062 DNA samples have been obtained from consented subjects. Another 1,774 DNA samples have been obtained from blood relatives of CHD subjects. DISCUSSION: The WPCR operates as a specialized resource of genetic and environmental information on children with CHD for researchers focusing on the multifactorial causes of CHD. PMID- 22097701 TI - Evolution of an integrated public health surveillance system. AB - There is a growing recognition in maternal and child health of the importance of social, behavioral, biological, and genetic factors across the entire life course. Unfortunately, most state maternal and child health surveillance systems are not designed to readily address longitudinal research questions or track and follow children across multiple programs over time. The Virginia Department of Health (VDH) recently integrated its birth defects registry, newborn hearing screening tracking and management system, and electronic birth certificate (EBC) into a robust, Web-based surveillance system called the Virginia Vital Events and Screening Tracking System (VVESTS). Completely redesigning the existing birth defects and newborn hearing screening system (the Virginia Infant Screening and Infant Tracking System--VISITS I) with minimal disruption of ongoing reporting presented a number of challenges. Because VVESTS had different requirements such as required fields and data validations, extensive data preparation was required to ensure that existing VISITS I data would be included in the new system (VISITS II). Efforts included record deduplication, conversion of free text fields into discrete variables, dealing with missing/invalid data, and linkage with birth certificate data. VISITS II serves multiple program needs; improves data quality and security; automates linkages within families, across programs, and over time; and improves the ability of VDH to provide children with birth defects and their families necessary follow-up services and enhanced care coordination. PMID- 22097703 TI - The relative contribution of data sources to a birth defects registry utilizing passive multisource ascertainment methods: does a smaller birth defects case ascertainment net lead to overall or disproportionate loss? AB - Since 1998, the Florida Department of Health (FDOH) has operated the Florida Birth Defects Registry (FBDR), a statewide, population-based, passive surveillance system. Cases are identified by collecting information from extant data sources including the statewide hospital inpatient and ambulatory discharge data sets. Additional data sources include administrative, clinical, and service related information from the FDOH's Children's Medical Services program for children with special health care needs. Like many state birth defects programs, the FBDR faces diminishing funding and resources that may restrict the registry to hospital discharge data. We conducted an evaluation to quantify the potential under-ascertainment to the FBDR resulting from loss of specific data sources, and to determine if there would be a disproportionate loss of cases by sociodemographic and perinatal characteristics. Analyses involved a series of retrospective reconstructions of the FBDR for 1998-2007 to assess the number of cases that would have been ascertained and reported based on the hypothetical loss of 1 or more of the FBDR source data sets. The reconstructed number of cases identified for each defect category was then compared to the current FBDR (constructed using all 5 source data sets) to determine the proportion of cases that would have been missed if the data sources in question were eliminated. These scenarios were constructed overall and by selected characteristics to identify potential disparities in the proportion of cases missed. The inpatient hospital discharge data set was the primary data source for identification of birth defects in the FBDR. Elimination of this single data source would cause the FBDR to miss nearly three fourths of infants diagnosed with 1 or more of the birth defects under study. Our evaluation revealed that an FBDR constructed on hospital discharge data alone would disproportionately miss more cases born to subgroups of women, including non-Hispanic blacks, Hispanics, and those born outside the US. Despite funding and resource constraints, the FBDR continues efforts to identify data sources that may contribute to completeness of case ascertainment in an effort to serve the needs of the Florida maternal and child health population. PMID- 22097704 TI - The Collaborative Stage Version 2 Data Validation Project, 2010. AB - The Collaborative Stage Data Collection System (CS), used to collect cancer information and derive stage values, was extensively revised in response to revisions in the American Joint Committee on Cancer's AJCC Cancer Staging Manual seventh edition, published in 2010. CSv2 was released to the cancer registry community for use in January 2010. In February 2010 the CSv2 Project management team authorized the data validation project to review the content and formatting of the data tables and make recommendations to the CSv2 mapping team for modifications to the tables. This article describes the review process, problems identified and resolved, and results: 1453 new codes, 340 converted codes, 301 codes marked for manual review, 6 new types of data tags, 3 new version numbers, changes in table notes, changes in construction of intermediate tables, and changes in tables which combine AJCC TNM components into stage assignments. The purpose of this article is to help software vendors, registry users, and data analysts understand the changes they will see as they implement the new version, CSv2:V0203. Also, as vendors, users, and analysts become aware of the complexities and limitations of the current system and processes, and the considerations involved in modifying the system, evident to those working on the project, it is hoped that the review presented in this article will inform ongoing discussions about the future management and development of the Collaborative Stage Data Collection System. PMID- 22097705 TI - The Rapid Quality Reporting System--a new quality of care tool for CoC-accredited cancer programs. PMID- 22097707 TI - Is it reportable? PMID- 22097706 TI - Raising the bar: rejuvenating the cancer registrar. PMID- 22097708 TI - [Development and application of the physical hypoxic models of C. elegans]. AB - OBJECTIVE: To develop a suitable hypoxic injury model, which is important for revealing pathological molecular mechanism of hypoxia. METHODS: We focused on C. elegans by treatment with different hypoxic times and systematically observed mortality, movement, Cellular morphology and the related-protein expression of the animals. RESULTS: We demonstrated that hypoxia (0.2% partial pressure of oxygen) induced morphological cell defects, and then leading to death of C. elegans. The mortality of C. elegans increased along with hypoxic time, while hypoxia-inducible factor (HIF-1) was significantly up-regulated. In addition, by using neuron-specific transgenic wonns with green fluorescent protein--we observed the neuron-specffic injury caused by hypoxic stress. CONCLUSION: We successfully established an effective, convenient physical hypoxic model of C. elegans, which will facilitate the studies of hypoxic pathology and molecular mechanisms of hypoxic response in the future. PMID- 22097709 TI - [Effects of hypoxia to rat diaphragmatic discharge]. PMID- 22097710 TI - [The effects of chronic stress on spatial cognitive ability of different sex mice]. AB - OBJECTIVE: To investigate the effects of chronic stress on spatial cognitive ability in different sex mice. METHODS: Thirty-two adult KM mice were divided into four groups (n=8): male control and chronic stress group, female control and chronic stress group. We used the modified Kaz's methods to build on the chronic stress model of mice, and then used the place navigational testing and the probe trial testing by the Morris water maze to measure the spatial cognitive ability of mice. RESULTS: Following two weeks stress treatment, in the place navigational testing, to male group, the average latency to find the platform in water maze of chronic stress group was longer than that of the control; to female group, the average latency of chronic stress group was shorter than the control. Moreover, the male stress group showed faster swimming speed but longer latency to find the platform. In the probe trial testing the female chronic stress group spent more time in the target quadrant compared to the male chronic stress group. CONCLUSION: Two weeks' chronic stress could impair male mice's spatial cognitive ability, but improve the female's. PMID- 22097711 TI - [The research of total flaveos of Gymostemma pentaphyllum (Thunb)Mak drug serum on calcium ion and NOS-NO system in cardiomyocytes injured by hypoxia and reoxygenization]. PMID- 22097712 TI - [Changes of endoplasmic reticulum stress-induced apoptosis in pulmonary tissue of rats with hypoxic pulmonary hypertension]. AB - OBJECTIVE: To investigate the changes of endoplasmic reticulum stress-induced apoptosis in pulmonary tissue of rats with hypoxic pulmonary hypertension. METHODS: Twenty two male SD rats were randomly divided into control group and 4 week hypoxia-hypercapnia group (n=11). The mean pulmonary arterial pressure (mPAP) and the mean carotid arterial pressure (mCAP) were monitored, and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV + S) were measured. The rattish pathological model were assessed by mPAP, mCAP, RV/(LV+ S), vessel wall area/total area (WA/TA), vessel cavity area/total area (CA/TA) and media thickness of pulmonary arteriole (PAMT). The pulmonary apoptotic cells were detected by Hoechst staining. RT-PCR was used to study the genetic expression of caspasel2, glucose regulated protein 78 (GRP78) and GRP94 in pulmonary tissue. The expression of GRP94 and GRP78 proteins in pulmonary tissue were determined by using immunohistochemistry. RESULTS: (1) (The mPAP, RV/(LV + S), WA/TA and PAMT were respectively higher by 50.5%, 37.3%, 72.5% and 137% in hypoxic group than those in control group, while CA/TA was lower by 41.9% (all P < 0.01). There was not significant difference of mCAP between the two groups. (2) Hoechst staining showed that the pulmonary apoptotic cells in hypoxic group outnumbered markedly than those in control group, and the apoptotic cells were mainly in pulmonary tissue, while they were rare in pulmonary vascular smooth muscle cell. (3) Compared with control group, the expression of pulmonary caspasel2, GRP78 and GRP94 mRNA in hypoxic group were higher by 144%, 137% and 80.7% (all P < 0.05), respectively. (4) The expression of pulmonary GRP78 and GRP94 proteins were up regulated in hypoxic group, and these proteins mainly localized in pulmonary vascular endothelial cell. CONCLUSION: The endoplasmic reticulum stress-induced apoptosis may be one of the mechanism of hypoxic pulmonary hypertension and pulmonary vascular wall remodeling. PMID- 22097713 TI - [Expression of mRNA for MCP-1 and CCR2 in cerebral tissue of rats with acute alcoholism]. PMID- 22097714 TI - [Effect of neotype carbonic anhydrase target-based inhibitors(P-8) on the hypoxic tolerance in mice]. AB - OBJECTIVE: To explore the effects of different doses of P-8 in increasing the Hypoxia tolerance of mice and the mechanisms involved. METHODS: The health mice were placed into the oxygen deficit bottles and measured the survival time in the condition of hypoxia. The male mice were put into the ladder cage, then placed them into the hypobaric champer to determine the survival time of mice with decompression hypoxia (min). We observed the activity changes of the mice's organization carbonic anhydrase II (CAII). By using the drug in prophylaxis, we investigated the effects of carbonic anhydrase target-based inhibitors P-8 for improving the hypoxia tolerance. RESULTS: (1) In improving the endurance of mice in the condition of hypoxia, the survival time of 6.25 mg/(kg x d) and more doses of P-8 groups were (27.38 +/- 4.63, 29.53 +/- 4.43, 29.67 +/- 7.28, 31.55 +/- 6.34, 32.45 +/- 6.65, 36.81 +/- 7.24 and 35.41 +/- 4.20) min, compared with the control group (22.90 +/- 3.19) min , the survival time significantly prolonged (P < 0.05, P < 0.01); compared to the same dose of acetazolamide groups (24.54 +/- 3.17, 22.70 +/- 3.04, 22.67 +/- 2.99, 23.93 +/- 0.96, 27.87 +/- 5.06, 30.79 +/- 5.12 and 35.14 +/- 6.46) min, the survival time significantly prolonged; P-8 groups and Acetazolamide's minimum effective dose were 6.25 and 100 mg/(kg x d), the potency of P-8 is 16 times Acetazolamide. (2) In improving the endurance of mice in the condition of hypoxia, the survival time of middle and high doses of P 8 groups [(24.82 +/- -3.92, 28.27 +/- 5.89) min] were significantly longer than those in control group [(21.96 2.51) min, P < 0.05]; compared with the acetazolamide (23.11 +/- 3.71) min, the survival time of high dose of P-8 group was significantly prolonged. (3) Compared with the normal control group, P-8 [(25 mg/(kg x d), 50 mg/(kg x d), 100 mg/(kg x d), 200 mg/(kg x d)] dose groups inhibited the activity of carbonic anhydrase II (CAII) in the renal (P < 0.05, P < 0.01); P-8 [100 mg/(kg x d) and 200 mg/(kg x d)] dose group significantly inhibited the activity of carbonic anhydrase II (CA II) in the brain (P < 0.05). CONCLUSION: P-8 treatment improved the endurance of mice in the condition of hypoxia and worked better than Acetazolamide. The mechanism may be related to the inhibition of carbonic anhydrase organization. PMID- 22097716 TI - [Role of toll-like receptor 4 in the asthmatic rat airway smooth muscle cells proliferation and apoptosis]. AB - OBJECTIVE: To explore the role of Toll like receptor 4(TLR4) in the asthmatic rat airway smooth muscle cell (ASMCs) proliferation and apoptosis. METHODS: Established rat model of asthma,isolated and cultured rat ASMCs in asthma, using methods of small molecule RNA interference technology and lipofection method, for small molecule RNA-TLR4 transfection, detected proliferation of ASMCs by MIT minim colorimetry, apoptosis of ASMCs by TUNNEL, the expression of TLR4 protein and mRNA were detected by Western blot and RT-PCR in cells. RESULTS: The proliferation of ASMCs in TNF-alpha group were significantly higher than that in control group and siRNA-TLR4 transfection group and TNF-alpha + siRNA-TLR4 transfection group respectively and the proliferation of ASMCs in siRNA-TLR4 transfction group was lower than that in control group. The apoptosis rate of ASMCs in TNF-alpha group was lower than that in control group, siRNA-TLR4 transfection group and TNF-alpha + siRNA-TLR4 transfection group respectively and the apoptosis rate of ASMCs in siRNA-TLR4 transfection group and TNF-alpha + siRNA-TLR4 transfection group were significantly higher than those in control group. The mRNA and protein expression of TLR4 in control group and TNF-alpha group were significantly higher than those in siRNA-TLR4 transfection group and TNF-alpha + siRNA-TLR4 transfection group. The mRNA and protein expression of TLR4 in TNF-alpha group were significantly higher than those in control group (P < 0.01). CONCLUSION: Activation of TLR4 may contribute to asthmatic airway smooth muscle cell proliferation, inhibiting apoptosis and play an important role in airway remodeling in asthma. PMID- 22097715 TI - [Influence of acute hypoxia on CHL1 expression in different tissues of mice]. AB - OBJECTIVE: To observe the effects of acute hypoxia on the cell adhesion molecule close homologue of L1 (CHL1) expression in different brain areas and main organs (heart, lung, kidney) of mice, and provide a basis for the role of CHL1 in hypoxia injury. METHODS: Mice were randomly divided into two groups (n=10): normoxia group and hypoxia group. Hypoxia group were treated by acute hypoxia (8% O2, 8 h). Protein expression changes in different tissues were evaluated by Western blot. RESULTS: In central nervous system, CHL1 protein expressions were down-regulated in cerebral cortex, hypothalamus and brain stem by acute hypoxia and up-regulated in cerebellum. In heart and lung, CHL1 protein expression were down-regulated by acute hypoxia. CONCLUSION: CHL1 protein expressions were changed in different tissues after acute hypoxia, which suggested CHL1 might play an important role in hypoxia damage regulation. PMID- 22097717 TI - [Changes of NGFI-B subcellular location in cardiomyocytes of stressed rats and its biological effects]. AB - OBJECTIVE: To investigate the changes of expression and subcellular location of nuclear growth-induced protein-B(NGFI-B) in cardiomyocytes of stressed rats and its biological effect and to provide scientific evidences for exploring the mechanism underlying myocardium injury induced by stress. METHODS: The cell model of stress-induced cardiomyocyte injury were established. Western blot method and confocal microscopy method were used to investigate the subcellular location of NGFI-B in cardiomyocytes under stress. The flow-cytometry was selected to detect the apoptotic rate in cardiomyocytes in vitro. Western blot method was used to determine the content of cytochrome C protein in mitochondria and cytoplasm respectively. RESULTS: Stress induced the increase of NGFI-B content in the mitochondria of cardiomyocytes and the translocation of NGFI-B from the nucleus to the mitochondria. The translocation of NGFI-B promoted the release of cytochrome C from the mitochondria and the cardiomyocyte apoptosis. Treatment of stressed cardiomyocytes with leptomycin B, a non-specific blocker of nuclear export, resulted in nuclear retention of NGFI-B and abrogated its ability to induce the release of cytochrome C from the mitochondria. CONCLUSION: Stress could induce NGFI-B translocation from the nucleus to the mitochondria in cardiomyocytes, which activated the mitochondrial pathway of cell apoptosis. PMID- 22097718 TI - [Effects of iptakalim on pressure-overload induced cardiac remodeling and plasma PGI2 content in rats]. AB - OBJECTIVE: To study the effects of iptakalim (IPT) on pressure-overload induced cardiac remodeling in rats, and investigate correlation between this protection effects and plasma PGI2 content. METHOD: The pressure-overload induced cardiac remodeling model was induced by abdominal aorta constriction for 6 weeks, and the rats were divided into 5 groups repectively: (1) sham group, (2) control group, (3) IPT 3 mg/kg group (IPT 3), (4) indomethacin 2 mg/kg group (Indo 2), (5) indomethacin 2 mg/kg + IPT 3 mg/kg group (Indo 2 + IPT 3). RM6000 eight channel physiological recorder was used to record haemodynamics index, heart weight was weighed and the cardiac remodeling index was calculated, HE stain and Masson's stain were employed to perform histological analysis, colorimetric method was used to detect the hydroxyproline content in cardiac tissue, radioimmunological method was used to measure the plasma PGI2 content. RESULTS: After 42 days of aortic banding, the hyperdynamic circulation state, cardiac remodeling and decreased plasma PGI2 content were observed in the model group compared with those in the sham group, which were effectively reserved by treatment with IPT 3 mg/kg. Single-use indomethacin led to further deterioration of this pathophysiological changes, however, combination administration of IPT 3 mg/kg prevented these from worsening characteristic by ameliorating hyperdynamic circulation state and cardiac remodeling, augmnent plasma PGI2 content. CONCLUSION: IPT can significantly reverse abdominal aorta binding/pressure overload induced cardiac remodeling, its mechanism may contribute to binding K(ATP) channel in endothelial cells, ameliorating endothelium cells function, augmenting PGI2 synthesis and secretion. PMID- 22097719 TI - [The correlation, between expression of stanniocalcin-1 gene and level of hydrogen peroxide in tissue during cutaneous scand repair in mice]. PMID- 22097720 TI - [The relationship between endogenous hydrogen sulfide system and pulmonary hypertension induced by hypoxic hypercapnia]. AB - OBJECTIVE: To investigate the changes of the endogenous hydrogen sulfide(H2S) system in pulmonary hypertension induced by hypoxic hypercapnia (HHPH) in rats and approach the possible mechanisms. METHODS: 20 SD rats were randomly divided into control group (C) and hypoxic hypercapnia group (HH) (n=10). The changes of hemodynamics and the right ventricle/left ventricle + septum (RV/LV + SP) were measured. The ratio of vessel wall area and total area (WA/TA) of arteriae pulmonalis were observed under lightmicroscope. By using TdT-mediated dUTP nick end labeling (TUNEL) and immunocytochemistry techniques, apoptosis index (AI) and expression of Bcl-2, Bax protein in arteriae pulmonalis were tested. Plasma level of H2S and activity of H2S generating enzymes in homogenates of rat lung tissue were evaluated by sensitive modified sulfide electrode method. Cystathionine gamma-lyase (CSE) mRNA in lung tissues was determined by RT-PCR. RESULTS: The level of mean pulmonary arterial pressure(mPAP), WA/TA and RV/LV + SP were significantly higher in HH group than those in C group (P < 0.05 or P < 0.01). Compared with those in C group, the AI of arteriae pulmonalis in HH group were significantly lower; the expression of Bcl-2 protein increased while that of Bax protein decreased, and the ratio of Bax/Bcl-2 went up obviously (all P < 0.01). Plasma level of H2S, the activity of H2S generating enzymes and CSE mRNA in HH group were significantly lower than those in C group (all P < 0.01). Plasma level of H2S, the activity of H2S generating enzymes, CSE mRNA each was closely positively related to Al while inversely related to mPAP and Bcl-2/Bax (all P < 0.01). CONCLUSION: The endogenous hydrogen sulfide system is closely related to pulmonary hypertension induced by hypoxic hypercapnia. The depression of the H2S/CSE system in HHPH may help increase the ratio of Bcl-2/Bax, inhibit apoptosis of pulmonary artery smooth muscle cells and finally result in the formation of pulmonary hypertension. PMID- 22097721 TI - [Intermittent hypoxic preconditioning promotes altitude acclimatization: the duration and efficacy after cessation of hypoxic preconditioning]. PMID- 22097722 TI - [Correlation between MPO 129 A/G polymorphism and severity of coronary artery disease]. AB - OBJECTIVE: To explore the relationship between myeloperoxidase (MPO) 129 A/G promoter polymorphisms and the severity of coronary artery disease (CAD). METHODS: The study enrolled 267 patients who had been diagnosed as coronary artery diseases by coronary angiography. The serum MPO activity was detected by colorimetric method. PCR-RFLP method was used to decide the genotypes of the patients. The severity of CAD was evaluated by the numbers of stenotic coronary arteries and the Gensini scores respectively. RESULTS: The MPO 129 locus G and A alleles frequency were 0.893 and 0.107, respectively. No significant difference was observed in serum MPO activity between different genotypes (P > 0.05). The distribution of genotypes in different Gensini score groups had no significant difference (P > 0.05). The patients with GG genotypes were prone to develop mutivessel diseases. CONCLUSION: No significant correlation exists in MPO 129 locus polymorphism and serum MPO activity. The MPO 129 locus polymorphism isn't a reasonable predict factor of CAD severity. PMID- 22097724 TI - [The effects of high fat diet and endurance exercise on the aorta wall structure of experimental animal]. AB - OBJECTIVE: Based on high fat diet induced the model of atherosclerosis (AS) in C57BL/6J mice, authors studied the effect of endurance exercise on the atherosclerostic formation. METHODS: Forty eight 8-week-old C57BL/6J mice were divided into four groups randomly (n=12): control (group N), 12-week atherosclerosis model group(group H), 12-week atherosclerosis model plus 11-week treadmill training group (group H + E) and 22-week atherosclerosis model group (group HS). Then, we observed the effects of endurance exercise on the ultra structure of aorta by electron microscope. RESULTS: Twenty weeks of high fat diet could result in serious AS in mice while endurance exercise could significantly antagonize or restrain the occur of AS. In addition, 10 weeks of endurance exercise could alleviate the symptom of pathological changes which already happened on aorta wall. CONCLUSION: It indicated that endurance exercise could effectively prevent and cure AS that induced by high fat diet. PMID- 22097723 TI - [The effect of 5-HD on expression of PKC-alpha in rats of chronic hypoxic pulmonary hypertension]. AB - OBJECTIVE: To investigate the effect of mito chondrial K(ATP) channels (mitoK(ATP)) inhibitor 5-hydroxydecanoate(5-HD) on chronic hypoxic pulmonary artery hypertension (CHPAH) rats and its underlying mechanisms. METHODS: Forty eight male SD rats were equally divided into 4 groups randomly (n=12): normal group, hypoxia group, hypoxia + 5-HD group, hypoxia + Diazoxide group. Except the first group, the other three groups were put into hypoxic [O2 (10.0% +/- 0.3%] and nonrmobaric chamber for four weeks to establish chronic hypoxic model and received different interference. When the interference completed, right heart catheter was used to detect the mean pulmonary arterial pressure (mPAP) of each rat and PKC-alpha mRNA expression in pulmonary arteries was detected by reverse transcription-polymerase chain reaction (RT-PCR) and protein expression by Western blot. RESULTS: (mPAP was much higher in hypoxia group than that in normal group (P < 0.01) while in hypoxia + 5-HD group and hypoxia + diazoxide were decreased significantly compared to hypoxia group (P < 0.01). (2) The protein and mRNA levels of PKC-alpha in the hypoxic group were higher than those in normal group (P < 0.05). CONCLUSION: 5-HD plays a protective role on CHPAH. The mechanism of its effect may be attributed to inhibiting MitoK(ATP). PMID- 22097725 TI - [Effects of rapid eye movement sleep deprivation on recall of fear extinction in rats]. PMID- 22097726 TI - [The study on protective effect of sphingosine-1-phosphate in cardiomyocytes]. AB - OBJECTIVE: To explore the mechanism of protective effect of Sphingosine-1 phosphate(S1P) in cultured neonatal rat cardiomyocytes dining simulated hypoxia/reoxygenation. METHODS: On the basis of culturing neonatal rat cardiomyocytes, the model of hypoxia-reoxygennation was built by using method of Liquid Paraffin covering, the impact of S1P on apoptosis and p-Akt and mitochondrial membrane potential were studied by using method of Propidine Iodide staining and Western blot and Bhodanmine123 staining. RESULTS: SiP could reduce apoptosis rate (P < 0.01) and stabilize the mitochondrial membrane potential (P < 0.05) and improved the level of p-Akt1 (P < 0.01) in hypoxia/reoxygenation cardiomyocytes significantly. But wonnannin could block these effects of S1P partially. CONCLUSION: SiP can obviously restrain apoptosis in curtured rat neonatal cardiomyocytes during simulated hypoxia/reoxygenation. Stabilization of mitochondrial membrane potential by P13K-AM signaling pathway is likely to play a role in protective action of S1P. PMID- 22097727 TI - [Research of the influence of jiawei "ba zhen soup" on the junior men's sanda athletes' testosterone, cortisone and hemoglobin]. PMID- 22097728 TI - [The expression of connective tissue growth factor in mast cells in the development of pulmonary fibrosis]. AB - OBJECTIVE: To investigate whether connective tissue growth factor (CGGF) is expressed in mast cells (MCs) in lung in the development of bleomycin (BLM) induced pulmonary fibrosis. METHODS: Thirty-two male SD rats were randomly divided into 2 groups: BLM group and control group (n=16). The rats in BLM group were received single intratracheal instillation of BLM (5 mg/kg), and the rats in control group received equal volume of 0.9% normal saline(NS) to BLM. The rats in each group were sacrificed for lung tissue sampling on day 14 and day 28 after intratracheal instillation respectively. As the index of the severity of pulmonary fibrosis, the content of hydroxyproline in lungs was analyzed by chloramine T method. Mast cells and CTGF expression in lungs were examined by toluidine blue stain and immunohistochemical assay respectively. RESULTS: (1) On day 28 after intratracheal instillation of BLM, the content of hydroxyproline in lungs of rats was higher than that of control rats (P < 0.01). (2) Compared to control rats, the rats on day 14 and day 28 after instillation of BLM showed increased number of mast cells (Both P < 0.01) and up-regulated CTGF expression (Both P < 0.01). (3) No CTGF immuno-positive MCs were seen in the lungs of control rats whereas CTGF immuno-positive MCs were observed in the pathological areas in lungs of rats on day 14 and day 28 after BLM. CONCLUSION: CTGF is expressed in MCs in lungs in the development of pulmonary fibrosis, which might be one of the mechanisms underling promoting effect of MCs on fibrosis in lung. PMID- 22097729 TI - [Study of tyrosinase gene mutation in oculocutaneous albinism type 1 patients]. AB - OBJECTIVE: To explore the patients' genotypes and the mutation spectrum of Tyrosinase (TYR) gene and the effects on protein structure and function in oculocutaneous albinism type 1 (OCA1). METHODS: The polymerase chain reaction (PCR) and sequencing techniques were applied to amplify and analyze the regions of exon, exonintron and promoter of TYR gene of 15 OCA1 probands and some of their parents. The protein structure and function were forecasted and analyzed by bioinformatics software. RESULTS: Sequencing result showed 11 kinds of mutations, including 5 missense mutations (W400L, R299H, E294K, R77Q and K142M), 3 nonsense mutations (R116X, R278X and G295X), 2 insertion mutation (929insC and 232insGGG) and 1 splice site mutation (IVS1-3C > G). The nosogenesis was related to the change of protein structure and function in four pathological mutations. CONCLUSION: It seemes that W400L is the frequent mutations, which accounted for about 30.0% in Chinese mainland OCA1 alleles. It is doable to make some reasonable interpretation about TYR gene nosogenesis by bioinformatics method. PMID- 22097732 TI - [MEK inhibitors suppressed expression of NOS in spinal cord of morphine-induced dependent and withdrawal rats]. AB - OBJECTIVE: To explore the effects of intrathecal injection of mitogen-activated protein kinases inhibitors U0126 on the behavioral changes of morphine-induced dependent and withdrawal rats and the expression of nitric oxide synthase (NOS) in spinal cord. METHODS: All the rats were divided into 4 groups: control group, dependent group, withdrawal group, U0126 group (5 microg). Global withdrawal score, Touch evoked agitation scores (TEA score), immunohistochemical and Western blot technique were undertaken to evaluate behavioral changes and expression of FOS, nNOS and iNOS in spinal cord respectively. RESULTS: The results showed that intrathecal administration of U0126 significantly alleviated withdrawal symptom, withdrawal scores of U0126 group (22.5 +/- 4.09) were significantly lower than than those of withdrawal group (28.6 +/- 4.89) (P < 0.05). TEA scores of withdrawal group were 13.5 +/- 2.55, which were significantly higher than those of U0126 group (10.0 +/- 2.76, P < 0.05). Fos-like positive neurons in dorsal horn of withdrawal group were 380 +/- 71, which were higher than those of U0126 group(287 +/- 54, P < 0.05). Also nNOS and iNOS positive neurons in dorsal horn of U0126 group were 180 +/- 32, 10.8 +/- 2.8 respectively, which were significantly lower than that of withdrawal group (239 +/- 45, 16.8 +/- 5.1, P < 0.05). Compared with withdrawal group, levels of nNOS and iNOS protein in spinal cord of U0126 group were significantly lower. CONCLUSION: MEK inhibitors could alleviate withdrawal symptom of morphine-induced dependent rats and could suppress expression of NOS in spinal cord, and extracellular signal-regulate kinase (ERK) might involve the expression of NOS in spinal cord. PMID- 22097730 TI - [The effect of genetic polymorphism of the exon 2 of the beta-lactoglobulin gene on the milk composition in Chinese Holstein]. AB - OBJECTIVE: In order to study the effect of the polymorphism at the exon2 region of the (3-LG allele gene on milk composition and yield. METHODS: The single strand conformation polymorphism method (PCR-SSCP) was used to analyze for polymorphism the exon2 region of the 3-LG gene (NCBI accession number: DQ489319) in Chinese Holstein. RESULTS: Eight SSCP patterns were detected in the fragments: ab, abc, abd, abe, abcd, abce, abde and abcde, and the patterns frequencies as follows: 0.14, 0.10, 0.27, 0.23, 0.05, 0.04, 0.11 and 0.06 (P < 0.05); Six single nucleotide polymorphism (SNP) were detected in this study: sitel C>T, site2 T>C, site3 C>T, site4 C>C, site5 C> A, site6 A>T or C, and the polymorphism infonnation content (PIC) of these SNPs were in median or high polymorphism (PIC > 0.25). CONCLUSION: These SNPs at the exon2 region of the beta-LG gene were remarkably and affected milk performance traits (milk yield, protein and fat contents) in Chinese Holstein. PMID- 22097731 TI - [The effect of valsartan on the expression of the receptor for advanced glycation end products in human glomerular mesangial cells]. AB - OBJECTIVE: To elucidate the effect of valsartan on human glomerular mesangial cells oxidative stress and the expression of the receptor for advanced glycation end products (RAGE) induced by the advanced glycation end-products (AGEs). METHODS: Human glomerular mesangial cells were treated with advanced glycation end-product-bovine serum albumin (AGE-BSA) in the presence of valsartan. The reactive oxygen species (ROS) in cells were measured by Flow cytometry, and the mRNA of p47 phox, which was the primary subunits of NADPH oxidase, was detected by semi-quantitative reberse transcription polymerase chain reaction (RT-PCR). The mRNA of RAGE was detected by RT-PCR and the RAGE protein was assayed by immunocytochemistry. RESULTS: The product of ROS, and the expression of p47 phox and RAGE in mesangial cells, which were treated with AGE-BSA in the presence of valsartan, were down-regulated compared with the groups treated with AGE-BSA (P < 0.05). Valsartan dose-dependently and time-dependently inhibited the AGE-elicited overexpression of RAGE, ROS and p47(phox) in mesangial cells. CONCLUSION: Valsartan could inhibit RAGE expression through downregulation of oxidative stress. PMID- 22097733 TI - [Simultaneous telemetric analyzing of the temporal relationship for the changes of the circadian rhythms of brown adipose tissue thermogenesis and core temperature in the rat]. AB - OBJECTIVE: To measure simultaneously the time course for the circadian rhythm of brown adipose tissue(BAT) thermogenesis and core temperature, and analyzing their temporal relationship. METHODS: The circadian rhythm of core temperature (Tc), BAT temperature (T(BAT)), axillary temperature (Tax) and motor activity were simultaneously measured by telemetry in adult male Sprague-Dawley rats at an ambient temperature of 22 degrees C during a 12-h light:12-h dark photoperiod (lights on at 06:00 h and lights off at 18:00 h). RESULTS: (1) T(BAT) was 0.67 degrees C lower than Tc group under the light phase, but it was similar to that Tc during the dark phase. The rate of increase in T(BAT) was higher than corresponding increases in Tc at the start of transition from the light to dark phase, and increase in T(BAT) commenced approximately 8 min before Tc increases. Whereas at the start of transition from the dark to light phase, decrease in T(BAT) commenced approximately 4 min before Tc decreases. (2) The amplitude of the circadian Tax rhythm was similar to that of Tc. During either the light phase or dark phase, Tax was lower than simultaneous measurement of Tc. (3) Increases in behavioral activity commenced before increases in T(BAT) and Tc at the start of transition from the light to dark phase. CONCLUSION: BAT thermogenesis contributes to increase in core temperature during the dark phase, indicating that circadian changes of BAT thermogenesis does indeed play significant role in the overall maintenance of the circadian rhythm of core temperature. PMID- 22097734 TI - [Penehyclidine hydrochloride inhibits glutamate release and related research in global brain ischemia/reperfusion rats]. AB - OBJECTIVE: To investigate the effect of penehyclidine hydrochloride on glutamate (Glu)release and N-methyl-D-aspartate receptor (NMDAR)1 expression in hippocampus CA1 with global cerebral ischemia/reperfusion rats. METHODS: Sixty male Wistar rats were randomly allocated into three groups; group A received sham operation; group B received ischemia/reperfusion; group C received penehyclidine hydrochloride treatment (2 mg/kg) before ischemia/reperfusion (n=20). Global cerebral ischemia was induced according to Pulsinelli-Brierley method. All animals were divided into two experiments: (I) Microdialysis plus HPLC/FD were used to detect Glu level after reperfusion 1 h, 3 h, 6 h. (II) After reperfusion 3 h, the animals were decapitated on ice and the brains were immediately removed to detect NMDAR1 expression in CA1 area by immunohistochemistry. RESULTS: After penehyclidine hydrochloride treatment, extracellular Glu level in CA1 were significantly decreased compared with those of control group (P < 0.05 or 0.01); Total integrated OD, average gray value and positive-cell area of NMDAR1 in CA1 were also significantly decreased compared with those of control group (P < 0.05 or 0.01). CONCLUSION: Penehyclidine hydrochloride might has protective effect in hippocampus CA1 on global cerebral ischemia/reperfusion animals. The protective mechanism might be involved in inhibiting Glu release and NMDAR1 expression. PMID- 22097736 TI - [Effects of psychic ability and glutamine for different time sleep deprivation]. PMID- 22097735 TI - [Study on pancreas of type 1 diabetic mice induced by MLD-STZ using proteomics]. AB - OBJECTIVE: To get a better understanding of the mechanisms underlying type 1 diabetes mellitus, the differentially expressed pancreatic proteins from multiple low-dose streptozotocin (MLD-SIZ) mouse and normal mouse were analyzed and compared. METHODS: 20 male rats were separated into 2 groups (n=10): model mice treated with MLD-STZ and normal mice,differences of pancreatic proteome among in the two groups of mice, were analyzed by two dimensional polyacryamide gel electrophoresis (2DE). Protein quantification was analyzed and the differentially expressed spots were identified using mass spectrometry and MASCOT database searching. RESULTS: Compared with control group, 23 proteins had changed significantly in the model group, 8 proteins expression were up-regulated, 15 proteins expressions down-regulated significantly. Using MALDI-TOF-MS, 15 proteins with significant change were identified by peptide fingerprinting map and the results were searched in MASCOT database. The function analyzed showed that proteins with change were associated with metabolic, anti-oxidant, structural, catalytic enzymes and chaperone, et al. CONCLUSION: Type 1 diabetes is probably exerted via multi-target and multi-path mechanism. The proteins with significant change are newly target for type 1 diabetes early diagnosis and treatment. PMID- 22097738 TI - [Effect of total flavonoids from Chrysanthemun morifolium on learning and memory in aging mice]. AB - OBJECTIVE: To investigate the effect of total fiavonoids from Chrysanthemun morifolium (TFCM) on learning and memory, and cholinergic system function in aging mice. METHODS: The aging mice model was established by subcutaneous injection of D-galactose. ICR mice were divided into five groups (n=10): contrA group, model group, and TFCM groups. Mice in TFCM groups were given TFCM (50,100 or 150 mg/kg) by gastric irrigation once a day. Learning and memory ability were evaluated by Morris water maze test. The MDA content, SOD and Ach E activity were also measured. RESULTS: Compared with control group, learning and memory ability declined in the D-galactose-induced aging mice; meanwhile MDA content and AchE activity increased, SOD activity decreased. Treatment with TFCM (100, 150 mg/kg) ameliorated the decrease in learning and memory ability of aging mice. Compared with model group, TFCM (100, 150 mg/kg) could also decrease MDA content and Ach E activity, and increase SOD activity in aging mice. CONCLUSION: TFCM may improve the learning and memory ability of aging mice. The mechanism is involved in its antioxidative characteristic and improvement of central cholinergic system function. PMID- 22097737 TI - [Effect of ERK1/2 signaling pathway on astragaloside IV protects H9c2 cells against H2O2-induced oxidative injury]. AB - OBJECTIVE: To investigate whether Astragaloside IV(AST) protects H9c2 cells against H2O2-induced oxidative injury partly through ERK1/2 signaling pathway. METHODS: H9c2 cells oxidative injury was induced by 200 tmol/L H2O2 for 6 hours to establish the H2O2-induced injury model of H9c2 cells. The viability of H9c2 cells was detected using MTf method. Activity of lactate dehydrogenase(LDH), total-superoxide dismutase (T-SOD), manganese-superoxide dismutase (Mn-SOD) and content of MDA (malondialdehyde) in the culture medium were detected using colorimetric method. Western blot was performed to exam expression of p-ERK1/2 and ERK1/2 in H9c2 cells respectively. RESULTS: Under 200 micromol/L H2O2 treatment for 6 hours, the vaibility of H9c2 cells was suitable for the following study. Compared with H2O2 group, the cell viability was increased significantly in AST10 + H2O2 and AST2O + H2O2 groups (P < 0.01). The activity of LDH in the culture medium was decreased significantly (P < 0.01). The activity of T-SOD and Mn-SOD was increased significantly (P < 0.01), the content of MDA was decreased significantly (P < 0.01). Treated with 10 mg/L or 20 mg/L of AST, expression of p ERK1/2 in H9c2 cells injured from H2O2 was increased significantly (P < 0.01), when PD98059 (inhibitor of ERK1/2) was added, the effects of AST were cancelled. CONCLUSION: AST protects H9c2 cells against H2O2-induced oxidative injury partly through ERK1/2 signaling pathway. PMID- 22097739 TI - [Effects of nitric oxide on spontaneous pain reaction and neuronal apoptosis in the spinal cord of rats induced by formalin inflammatory pain]. AB - OBJECTIVE: To observe whether formalin inflammatory pain can induce neuron apoptosis in rats spinal cord or not and the effects of nitric oxide on the spontaneous pain reaction and neuron apoptosis in the spinal cord of rats with formalin inflammatory pain. METHODS: Formalin-induced paw licking time was used to reflect the degree of spontaneous pain of rats, and the flow cytometry was used to detecte neuron apoptosis rate of spinal cord. RESULTS: Compared with control group, the apoptosis ratio of spinal neuron was increased in the rats with formalin inflammatory pain, and peaked at 3d after formalin injection. Pre intrathecal injection of NOS inhibitor L-NAME inhibited the nociceptive behavioural response in double phases induced by fonnrmalin injection and cut down the neuron apoptosis ratio of spinal cord of rats with formalin inflammatory pain. Nociceptive behavioural response and incraesed neuron apoptosis in the spinal cord were induced by intrathecal injection of L-Arg in normal rats. CONCLUSION: The results indicated that formalin inflammatory pain could induce the apoptosis of spinal neurons. The neurons apoptosis was the most significant on the third day after formalin injection. The increased pruduction of NO in spinal cord could promote the transmit of nociceptive information and participate the induction of neuronal apoptosis during the formalin inflammatory pain. PMID- 22097741 TI - [Application of an improved tracheal intubation method during the preparation of myocardial infarction model in the mouse]. AB - OBJECTIVE: An improved tracheal intubation method was used in preparation of myocardial infarction model in the mouse for increasing the success rate. METHODS: The mice were intubated by an improved trachea cannula through oral cavity. The left anterior thoracotomy performed. The myocardial infarction model was made by legating the left anterior descending coronary artery in mouse. The color of heart was observed, and electrocardiogram was recorded. The survival rate and pathologic change were observed after two weeks of operation. RESULTS: 40 myocardial infarction model mice were made by improved trachea cannula. The color of ventricles anterior wall had got madder red, and ST stages were raised on II leads of electrocardiogram in all of model mice. After two weeks, 27 mice were survival. The survival rate was 87.1% except for accidental death during operation. The heart chamber expanded and ventricular wall became thin in myocardial infarction mice by eyes. After pathological sections were stained, by HE cardiac muscle fibers ruptured or lysed. There were some of necrosis of myocardiac cells and many of infiltration of inflammatory cells. CONCLUSION: Application of an improved tracheal intubation method simplified operation of tracheal intubation during preparation of myocardial infarction model in the mouse. The trauma was tinier than the other one, and achievement ratio of the model preparation was improved. PMID- 22097740 TI - [Changes of GABA-activated currents in isolated dorsal root ganglion neurons in rats with neuropathic pain]. AB - OBJECTIVE: To investigate the changes of GABA-activated currents in isolated dorsal root ganglion neurons in rats with neuropathic pain. METHODS: The neuropathic pain model was established by chronic constriction injury (CCI) 7 days before electrophysiological-recording. The rat DRG neurons were enzymatically dissociated. Whole-cell patch clamp technique was used to record GABA-activated currents. The changes of currents of injured side and opposite side were expected to compare with control group. RESULTS: (1) The currents of injured side of CCI group were notablely decreased compared with control group (GABA concentration, 0.1-1000 micromol/L). (2) By the contrast, opposite side currents of CCI group increased significantly compared with those in injured side and control group (GABA concentration, 0.01-1000 micromol/L). CONCLUSION: The data indicates that the chronic constriction injury change both the function of GABAA receptors of injury side and opposite side. The decrease of pre-synaptic inhibition of GABA may be the possible reason of neuropathic pain. PMID- 22097742 TI - [Design of power and data telemetry system utilizing Class-E amplifier for visual prosthesis]. AB - A wireless transmission system for visual prosthesis is introduced. Power and data are transmitted through inductive link between only one pair of coils, in order to reduce the size of the device. The transmitter is based on Class-E power amplifier due to its high efficiency, and a modulation circuit is added to control the dc supply of the Class-E amplifier to achieve ASK modulation of data with modulation depth of 25%. In addition, an experimental system is implemented, and test shows that it sufficiently supports a 16-channel micro-stimulator on power delivery and data transfer rate. PMID- 22097743 TI - [An adaptive filtering algorithm applied to inhibit the interference from the ventricular during atrial epicardial mapping experiment]. AB - This paper introduces an adaptive filtering algorithm based on the LMS principle to inhibit the ventricular interference in the atrial epicardial mapping experiments. PMID- 22097744 TI - [A model of blood pressure measurement which based on NN with raised accuracy]. AB - To address the accuracy problem of the oscillometric method in electronic blood pressure monitor, this paper introduces a more accurate new blood pressure measurement model, which based on ANN. And simulation checking method is put forward. PMID- 22097745 TI - [Application of algebraic reconstruction technique of multi-source tomosynthesis in dynamic reconstruction]. AB - To reduce the motion artifacts, a new scanning configuration is proposed for tomosynthesis in dynamic reconstruction. In this new configuration, multiple x ray sources are uniformly distributed on the circular scanning trajectory and moving simultaneously. Numerical experiments are performed using two dynamic digital phantoms and algebraic reconstruction technique. The reconstruction images of single-source tomosynthesis and multi-source tomosynthesis are compared and evaluated. The results show that multi-source tomosynthesis could reduce artifacts effectively, thus improving image quality. The advantages of multi source tomosynthesis in dynamic reconstruction are important to cardiac imaging and respiratory imaging. PMID- 22097746 TI - [An improved auto-window algorithm for MR image]. AB - When MR image's area is too small compared with the whole picture, the use of the current auto-window algorithms usually gets poor clarity and contrast. In order to address this problem, an improved auto-window algorithm is proposed in this paper and can solve the problem effectively and get clear and rich layers of MR images quickly and easily. PMID- 22097747 TI - [Comparison of two coils for MR angiography based on the SDNR method]. AB - In this paper, signal-to-noise ratio (SNR) and signal different-to-noise ratio (SDNR) methods were used to compare image quality using two different radiofrequency coils. The two coil types included an eight-element phased-array coil and a quadrature birdcage head coil with endcap and the comparison studies performed on a uniform cylindrical phantom and volunteer respectively. The results showed phased-array coil have advantages and proved effectiveness of the method in the evaluation and selection of coils. PMID- 22097748 TI - [Study on diagnostic methods of breathing disorders based on fuzzy logic inference and the neural network]. AB - This paper descries a new non-invasive method for diagnosis of breathing disorders based on adaptive-network-based fuzzy inference system (ANFIS). In this method, PetCO2, SpO2 and HR are chosen as inputs, and the breathing condition is selected as output ofANFIS. The inputs and output are then classified into fuzzy subsets by experts' knowledge. After, the fuzzy IF-THEN rules are built up according to the corresponding membership functions by set up of fuzzy subsets. The neural network was finally established and the membership functions and fuzzy rules were optimized by training. The results of experiment shows that ANFIS is more effective than BP Network regarding the diagnosis of breathing disorders. PMID- 22097749 TI - [Study for lung sound acquisition module based on ARM and Linux]. AB - A acquisition module with ARM and Linux as a core was developed. This paper presents the hardware configuration and the software design. It is shown that the module can extract human lung sound reliably and effectively. PMID- 22097750 TI - [Design of a medical folding fridge]. AB - This article introduces a design of a medical folding fridge, which consists of three major components, base, folding frame and insulated cover. The base has a cooling system. The frame and cover are expanded during normal use and folded during storage or transportation. The device is compact, durable, transportable and well environmental adaptable. The system design is proved proper and the temperature inside is reliable. It is very suitable for temperature sensitive supplies stored in the medical emergency field. PMID- 22097751 TI - [Summary about the progress and specifications of FDA regarding intravascular catheters]. AB - This article summarizes the progress and specifications of FDA regarding intravascular catheters, and hope this would be helpful to people concerned. PMID- 22097752 TI - [Ethic review on clinical experiments of medical devices in medical institutions]. AB - Clinical experiments are always used to evaluate the safety and validity of medical devices. The experiments have two types of clinical trying and testing. Ethic review must be done by the ethics committee of the medical department with the qualification of clinical research, and the approval must be made before the experiments. In order to ensure the safety and validity of clinical experiments of medical devices in medical institutions, the contents, process and approval criterions of the ethic review were analyzed and discussed. PMID- 22097753 TI - [Some perspectives of management in the use of medical devices]. AB - The improper selection, management or use of medical devices may lead to a disproportionate rise in the cost of healthcare, which has concerned many countries. Some perspectives of management in the use of medical device have been widely discussed in 1st global forum on medical devices held by the World Health Organization on Thailand in 2010. This paper presents some main perspectives about this. PMID- 22097754 TI - [Analysis of FDA medical device recall in 2005-2006]. AB - OBJECTIVES: To analyze medical device recall information of FDA U.S. and to address the safety issue of medical device. METHOD: For each report, the recall class, product name, product class and recall reason were recorded and classified for analysis. RESULTS: 3093 reports were identified; the recalling reasons of the three classes were significantly different. It is found that the main recall reason for medical material is package problems (39%) and design defectiveness (19%), for medical tools are design defectiveness (27%) and package problems (26%), and for medical equipment are design defectiveness (45%) and system failures (39%). The number of software recalled is 109. The main recall reason for high risk equipment is design defectiveness, and the I class level of high risk equipment recalled was decline in 2006 compared to that in 2005. CONCLUSION: Monitoring and application of medical device recall information should be strengthened, and the objective law of medical device safety issue should be summed up, in order to provide reference for supervision of medical device. PMID- 22097757 TI - [Emergency medical equipment safety and risk management]. AB - This paper analyzes emergency medical devices, and puts forward the types of risk management mode, risk analysis, risk assessment (including the risk score calculation), and risk control points. Emergency medical equipment which has the high risk and is directly related to the patient's life safety, should be taken seriously. PMID- 22097755 TI - [Research of the transformation and implementation of IEC60601-1 3rd edition in China]. AB - This paper discussed the possible influence of the transformation and implementation of IEC60601-1 3rd edition in China, and accordingly proposed some preliminary suggestions. PMID- 22097756 TI - [Review and experience on inter-laboratory comparisons of medical device testing]. AB - By Reviewing the Inter-laboratory Comparisons of Medical Device Testing for 5 times, the present paper summarizes several experience and thoughts in participating in inter-laboratory comparisons, and offers some suggestions. PMID- 22097758 TI - [A perspective of YY0709-2009 testing of alarm system for medical use]. AB - This paper introduces the meaning of YY0709-2009's issue and its scope. It emphasizes the details of visual and audible alarms. Reasonable suggestions to comply with these requirements are provided at the end of the article. It will be of help to understand YY0709-2009 and to manufacture or test the product under YY0709-2009. PMID- 22097759 TI - [fMRI functional connectivity analysis of anxiety disease patients based on spatiotemporal Lyapunov exponent method]. AB - Attempting to use nonlinear spatiotemporal Lyapunov exponent to characterize fMRI brain functional connectivity of anxiety disease patients, we adopted the methods of nonlinear spatiotemporal Lyapunov exponent and linear correlation coefficients to analyses fMRI datum of 11 anxiety disease patients and 11 healthy volunteers, respectively. The results show that there are significant normalized variance exponent (NVE) differences in Inferior Frontal Gyrus (rIFG) and Medial Frontal Gyrus (MFG) between the two groups (P<0.01). And correlation coefficients shows significant differences (P<0.05). The spatial-temporal Lyapunov exponent method had higher sensitivity than the correlation coefficient method in the characterization of functional connectivity; Anxiety disease patients have abnormal functional connectivity in rIFG and MFG during our experiment. PMID- 22097760 TI - [Some special problems about the usement of wedge field in radiation therapy]. AB - This article presents and discusses some special problems about the use of wedge field in radiation therapy according to the practice of the author. Thus we attain the rules of quality assurance in radiotherapy by WHO. PMID- 22097762 TI - [An implementation of constructing medical data integration platform based on web service]. AB - Using the technology of Web Service and the Development tools of MyEclipse, we design and realize a Medical Data Integration Platform. The plan can use the existing resources of the hospital adequately, simplify the integration of Medical Data, and have the nice extensibility and maintainability. PMID- 22097761 TI - [A preliminary study for starshot analysis during quality control of medical linacs]. AB - OBJECTIVE: This study was to discuss the influencing factors of Starshot analysis during the quality control of medical linacs. METHODS: During the quality control of a Siemens medical linac, Starshot analysis were carried out using FilmQA software and KODAK low sensitive films. The influence of setting to the results of Starshot analysis were explored, including Jaw width, shit of gantry angles, center shifts of Jaws, Beam energy and scan resolution. RESULT: The offset of Jaws's center had effect on the analysis result and the center offset was linearly related to the result. The influence of Beam energy and scan resolution was much smaller, and the maximum deviation was less than 0.2mm. The deviation for gantry angle at 4 degree was a little larger than 2 degree which deviation was less than 0.1mm.The Jaw width had greater effort on the analysis result, and two trends were found in 2 tests. CONCLUSION: In clinic, if the result of Starshot analysis was out of tolerance, a careful check to multi factors should be made before the last determination. PMID- 22097763 TI - [Malfunction analysis and preventive measures of CT equipment]. AB - After the analysis of the service and maintenance technology of CT equipment under the existing technical condition we conclude that although the CT equipment malfunctions vary with different manufacturer, they are predictable and preventable, based on the identical CT principle and similar construction of system. PMID- 22097765 TI - [Advances in clustered regularly interspaced short palindromic repeats--a review]. AB - The recently discovered Clustered Regularly Interspaced Short Palindromic Repeat (CRISPRs) can protect bacteria and archaea with adaptive and heritable defense systems against the invasion of phage- and plasmid- associated mobile genetic elements. Here, we review the structure, diversity, mechanism of interference and self versus non-self discrimination of CRISPR systems. We also discuss the potential applications of this novel interference system. PMID- 22097764 TI - [Discovery and research progress of endophytic bacteria in the root nodules of legumes--a review]. AB - Recently, some research reports showed varied endophytic bacteria in the root nodules of some legumes, which attracts great interest in research field of rhizobia. Here, we reviewed the discovery, identification of some endophytic bacteria (Agrobacterium, non-symbiotic rhizobia, and other bacteria) in root nodules and their influence on symbiosis or plant growth, to understand the microecosystem of root nodule and to extend the field of rhizobia research. PMID- 22097767 TI - [Studies on the actinobacterial diversity in aiding lake sediments]. AB - OBJECTIVE: This study aims at investigating the diversity of actinobacteria in Aiding Lake, a hypersaline lake and the lowest land point in China. METHODS: The diversity of actinobacteria in the sediment from Aiding Lake was investigated by culture--independent method based on phylogenetic analysis of 16S rRNA gene sequences and selective isolation. Specific primers were used to amplify the actinobacterial 16S rRNA gene, and corresponding clone libraries were constructed for the sediment samples. Different clones selected on the basis of Hae III digestion patterns were sequenced. Nine selective media with different salinities were used to isolate actinobacteria from the sediment samples. RESULTS: The analysis of 16S rRNA gene sequences showed that 273 clone sequences belonged to subclasses Actinobacteridae (208), Acidimicrobidae (13) and Rubrobacteridae (52). The dominant actinobacteria was genus Rothia, which accounted for 37% of total clones. The similarity between 45.8% of 273 detected sequences and published sequences were less than 97%, which might represent new taxa. Some sequences, which formed several distinct clades in phylogenetic tree may represent new taxonomical groups of actinobacteria. Fifty-five strains were isolated by different selective media. They belonged to six suborders of the order Actinomycetales, of which Streptomyces and Nocardiopsis were the dominant groups. Six potential new species were obtained. CONCLUSION: Aiding Lake harbors abundant actinobacteria, including large number of unknown actinobacterial groups. PMID- 22097766 TI - [Central metabolism of anammox bacteria--a review]. AB - Anaerobic ammonium oxidation (anammox) is a biological process by which ammonium is oxidized to dinitrogen gas by using nitrite as the electrons acceptor. Anaerobic ammonium-oxidizing bacteria play an important role in nitrogen removal from wastewater and global N-cycle. The study of metabolism of anammox bacteria will help us understand the anammox mechanism and develop anammox biotechnology. Anammox bacteria are chemoautotrophic bacteria that use CO, or HCO3- as carbon source and obtain their energy from the conversion of ammonium and nitrite into dinitrogen gas. Hydrazine has been detected as an intermediate in the anammox pathway, while hydroxylamine and nitric oxide have not been detected yet. The genomic data indicate that anammox bacteria fix carbon dioxide through acetyl-CoA pathway. The proposed anammox pathway is consistent with the available experimental data, thermodynamical calculation and biochemical determination and as well as the Ockham's razor principal. PMID- 22097768 TI - [Development of a genetic modification system for caerulomycin producer Actinoalloteichus sp. WH1-2216-6]. AB - OBJECTIVE: In order to enable the caerulomyicn biosynthetic study by in vivo gene disruptions, it is crucial to develop a genetic modification system for the producer Actinoalloteichus sp. WH1-2216-6. METHODS: The spore germination timing and the concentration of MgSO4 in the medium were investigated for the optimal conjugal transfer of exotic pSET152 DNA into Actinoalloteichus sp. WH1-2216-6. Using the PCR-targeting system, we disrupted a putative caerulomycin 2,3 dihydroxybenzoate-AMP ligase gene by "in-frame deletion" in E. coli, to afford the cosmid pCSG2104, which was then transferred into Actinoalloteichus sp. WH1 2216-6 by conjugation under optimized conditions. RESULTS: The putative caerulomycin 2,3-dihydroxybenzoate-AMP ligase in Actinoalloteichus sp. WH1-2216-6 was successfully disrupted by in-frame replacement with the aac3IV gene cassette. The resulting mutant strain was unable to produce caerulomycins. CONCLUSION: The presence of high concentration of MgSO4 in the medium can promote the conjugation efficiency between E. coli and Actinoalloteichus sp. WH1-2216-6 and lead to the successful development of a genetic modification system for Actinoalloteichus sp. WH1-2216-6, enabling the functional characterization of caerulomycin biosynthetic genes in vivo. A positive example was provided for other Actinobacteria recalcitrant to genetic modification. PMID- 22097769 TI - [Influence of predominant aerobic bacteria isolated from different healthy animals on daidzein biotransforming capacity by co-culture with different daidzein biotransforming bacteria]. AB - OBJECTIVE: To investigate the influence of isolated predominant aerobic bacteria on daidzein biotransformation capacity by co-culture with daidzein biotransforming bacteria. METHODS: Predominant aerobic bacteria were isolated from diluted feces solutions of different healthy animals, including ICR mice, Luhua chicken, Landrace pigs and Rex rabbits. Daidzein biotransforming bacteria were anaerobically co-cultured with the isolated predominant aerobic bacteria and the cultural broth was extracted and detected by high performance liquid chromatography (HPLC). RESULTS: Twenty two predominant aerobic bacteria were isolated from the four different healthy animals mentioned above. Based on the analyses of 16S rRNA gene sequences, morphology study and relative biophysico biochemical characteristics, all 22 isolates belong to the 5 genera, i. e. Escherichia (10) , Proteus (5) , Enterococcus (4), Bacillus (2) and Pseudomonas (1). Co-culture between predominant aerobic bacteria and daidzein biotransforming bacteria was carried out under anaerobic conditions. The results showed that the biotransformation capacity was totally lost when different daidzein biotransforming bacterium was co-cultured with either Bacillus cereus ( R1 ) or Pseudomonas aerginosa (R5) and continuously inoculated for 2 or 3 passages. However, no obvious influence was observed when daidzein biotransforming bacteria were co-cultured with all the other isolated predominant aerobic bacteria except R1 and R5. In addition, when strain R1 and R5 was co-cultured with the intestinal microflora of the ICR mice anaerobically and continuously inoculated for 5 passages, about 90% of the co-cultures totally lost the activity to convert daidzein to equol effectively. CONCLUSION: Different predominant aerobic bacteria showed different influence on daidzein biotransformation capacity after being co cultured with different daidzein biotransforming bacteria. Among all the isolated predominant aerobic bacteria used for co-culture, both Bacillus cereus ( R1) and Pseudomonas aerginosa (R5) were detected significant inhibition on biotransformation activity of different daidzein biotransforming bacteria. PMID- 22097770 TI - [High expression and characterization of N-acyl-homoserine lactonase-xylanase recombinant protein]. AB - OBJECTIVE: The fusion protein SL2B with both xylanase and N-acyl-homoserine lactonase activities was expressed in Pichia pastori. Characterization of the purified xylanase and N-acyl-homoserine lactonase fusion protein SL2B was investigated. METHODS: The fusion gene sl2b was amplified from the N-acyl homoserine lactonase gene aiiA-B546 and the xylanase gene xynAS27cd via overlap PCR technique. After the recombinant vector pPIC9/sl2b was transformed into P. pastoris, transformants with both xylanase and N-acyl-homoserine lactonase activity were screened. The purified SL2B was obtained with ammonium sulfate precipitation and molecular sieve. Both N-acyl-homoserine lactonase and xylanase activities of SL2B were characterized. RESULTS: The purified SL2B showed that the xylanase had optimal pH and temperature at pH 6.5 and 60 degrees C, respectively. The enzyme was stable between pH 6.0 and 8.0, retained over 80% enzyme activity between 50 and 65 degrees C. It resisted various neutral proteases and chemical reagents. With oat spelt xylan as substrate, the Km value of SL2B was 2.9 mg/L. The N-acyl-homoserine lactonase had optimal pH and temperature at pH 8.0 and 30 degrees C, respectively. The enzyme was stable between pH 4.0 and 10.0, retained over 80% enzyme activity between 0 and 50 degrees C. It resisted various neutral proteases and chemical reagents. The fusion protein can hydrolyze many N-acyl homoserine lactones substrates. With N-(3-oxo-octanoyl)-L-homoserine lactone as substrate, the Km value of SL2B was 0.050 mmol/L. CONCLUSION: High level expression is achieved by fusing N-acyl-homoserine lactonase to the xylanase. PMID- 22097771 TI - [Identification and denitrification of an aerobic bacterium]. AB - OBJECTIVE: Denitrifying bacteria play an important role in the biological nitrogen removal process, especially the aerobic denitrifying bacteria. However, there are few studies on aerobic denitrifying bacteria. The present study aimed at the isolation of aerobic denitrifying bacteria with high ammonium and nitrite nitrogen removing ability from environmental samples, and its phylogeny and denitrifying characteristics. METHODS: Based on the aerobic denitrifying activity, ammonium and nitrite nitrogen removing ability, the strains were isolated from sludge, water and sediment in a eutrophicated pond. A strain with the highest activities was identified according to its morphological, physiological and biochemical properties and phylogenetic analysis of its 16S rRNA sequence. By using NO(3-)-N, NH(4+)-N and NO(2-)-N as the sole nitrogen source respectively, its denitrifying characteristics, and the effects of culture conditions such as initial pH of medium, temperature, carbon source, shaking speed on the ability of removing ammonium and nitrite nitrogen, were investigated under aerobic condition. RESULTS: Among the isolated strains, strain C-4 showed the highest ability of removing ammonium and nitrite nitrogen. Strain C-4 was identified as Acinetobacter sp.. Under the conditions of sodium citrate as carbon source, temperature 30 degres C, shaking speed 120 r/min, cell age of 18 h, pH 8.5 for 200 mg/L NH(4+)-N medium and pH 7.5 for 100 mg/L NO(2-)-N medium, the net removal efficiency of nitrogen were 65.8% and 47.8% after 15 h and 12 h, respectively. CONCLUSION: An aerobic denitrifying strain Acinetobacter sp. C-4 (HQ896038) was isolated from water pond, and it exhibited high net removal efficiency of nitrogen in relative media. The net removal efficiency of nitrogen of strain C-4 was 73.04% in dealing with a eutrophicated pond water. PMID- 22097774 TI - Biodegradation of pyridine and quinoline by two Pseudomonas strains. AB - OBJECTIVE: To study the degradation of pyridine and quinoline by two Pseudomonas. METHODS: Based on the analysis of 16S rRNA gene sequence homology and the intergenic spacer region sequence, the two isolates were identified. The degradation capability of pyridine and quinoline was determined according to spectrophotometry and Electrospray Ionisation/Mass Spectrometry (ESI/MS). The degrading plasmids were detected by plasmid curing and the possible degrading genes were also cloned. RESULTS: The two isolates were identified as Pseudomonas and nominated XJUHX-1 and XJUHX-12. The two Pseudomonas were tolerant with pyridine and quinoline and two and four possible metabolites were detected in the culture medium containing quinoline and pyridine, respectively. The degrading capability of curing plasmids was lower than the crude isolates. The gene segments coding for the NADH (acceptor) reductase component OxoR for quinoline degradation and nitrogenase reductase (NifH) of denitrification for pyridine degradation were amplified from the genome of XJUHX-1 and XJUHX-12, both were cloned and expressed in E. coli BL 21 producing recombinant proteins with molecular mass of 43 kDa and 16 kDa. CONCLUSION: The two isolates could degrade pyridine and quinoline respectively. PMID- 22097772 TI - [Observation by transmission electron microscope and identification of endophytic bacteria isolated from Bursaphelenchus xylophilus and B. mucronatus]. AB - OBJECTIVE: The pine wood nematode, Bursaphlenchus xylophilus, morphologically similar to B. mucronatus, is the pathogen of pine wilt disease. This study was focused on the endophytic bacteria present in these nematodes. METHODS: Detailed observations were made on sections of all parts of the two types of nematodes by transmission electron microscope. The nematodes were surface-sterilized by soaking in 1% mercuric chloride and antibiotic mixture, and then ground and cultured on nutrient agar plate. The physiological and biochemical characteristics combined with molecular characterization of bacteria were analyzed and identified. RESULTS: Endophytic bacteria were found in intestines of the two nematodes by transmission electron microscope observations. On the basis of surface sterilization, total three bacteria strains were obtained from B. xylophilus and B. mucronatus. These bacteria belong to Stenotrophomonas and Ewingella. CONCLUSION: It confirms the presence of endophytic bacteria in Bursaphelenchus xylophilus and B. mucronatus and these bacteria may play a physical and ecological roles in nematodes. PMID- 22097773 TI - [Field resistance of Phytophthora melonis to metalaxyl in South China]. AB - OBJECTIVE: Phytophthora melonis is the casual agent of wax gourd and cucumber Phytophthora blight which becomes a constraint for sustainable production of the related crops. Metalaxyl is one of the principal fungicides for controlling the disease now. The objectives of the present study were: (1) to investigate the baseline sensitivity and field resistance of P. melonis to metalaxyl in South China; (2) to test the occurrence of metalaxyl-resistant mutants from metalaxyl sensitive wild type strains exposed to the fungicide; and (3) to monitor the development of metalaxyl resistance in P. melonis population. METHODS: Over 400 samples of wax gourd and cucumber Phytophthora blight were collected from Guangxi Zhuang Autonomous Region and Guangdong province during 2007-2010, and 193 strains of P. melonis were isolated and purified. The sensitivity of the isolated strains to metalaxyl was tested using mycelial growth rate method in vitro and floating leaf-disk method in vivo, respectively. The metalaxyl-sensitive strains were induced on PDA plates containing 10 microg/mL metalaxyl. RESULTS: The sensitive, moderately resistant and resistant strains were recorded as 29.0% , 18.1% and 52.8%, respectively, among 193 tested strains. The frequency and level of resistance of P. melonis from Guangdong were higher than that from Guangxi. The strains from cucumber was generally more resistant to metalaxyl than those from wax gourd. The metalaxyl-resistant strains were frequently detected as predominant populations in most of the sampling sites and the highest resistance index (4226.9) was confirmed. Metalaxyl-resistant (M1r) mutants could be isolated from approximately 60% of the sensitive wild-type strains. The resistance level of the M mutants was 189-407 times higher than that of their sensitive parental strains. The EC50 values of 9 sensitive strains from a sampling site without a record of phenylamide fungicide application ranged from 0.0429 to 0.5461 microg/mL. Their mean EC50 value (0.3200 +/- 0.1617 microg/mL) was considered as the baseline sensitivity of P. melonis to metalaxyl in South China. CONCLUSION: Metalaxyl-resistant strains universally occur in South China, especially in the vegetable-growing areas with a longer history of metalaxyl application. The establishment of the baseline sensitivity of P. melonis to metalaxyl will provide a science-based guide for evaluating and further monitoring resistance of the pathogen to the fungicide. PMID- 22097775 TI - [Insertion of glycoprotein gene between P and M gene influences the pathogenicity of the rabies virus Flury LEP]. AB - OBJECTIVE: To study the biological characteristics and pathogenicity of a recombinant rabies virus Flury LEP (low egg passage) that has two glycoprotein genes (G gene). METHODS: By using reverse genetics techniques, we constructed a recombinant virus Flury LEP that has an additional G gene between P and M gene (rLEP-PGM). Then we studied the biological characteristics of the recombinant virus and its pathogenicity on mice. RESULTS: The in vitro growth characteristic of rLEP-PGM were similar to the LEP strain. Western blot analysis of glycoprotein expression showed that the glycoprotein expression level of rLEP-PGM was 1.5 times higher than LEP. The LD50 of rLEP-PGM and LEP was 3 FFU and 1 FFU by intracerebral injection. However, the LD50 of intramuscular injection was 4 x 10(4) Lg FFU and 3.2 x 10(5) Lg FFU, respectively. CONCLUSION: Insertion of an additional G gene between P and M gene can significantly raise the expression level of glycoprotein and enhance the ability to invade central nervous system from peripheral sites. PMID- 22097776 TI - [High-throughput screening of human pancreatic alpha-amylase inhibitors]. AB - OBJECTIVE: Targeting the important enzyme in human glucose metabolic pathway, we established a high throughput screening model for human pancreatic alpha-amylase inhibitors. METHODS: Pichia pastoris expression system was used to clone and express the human pancreatic alpha-amylase; we established the alpha-amylase inhibitor screening model using the catalytic properties of enzyme; this model was applied in screening of actinomycete' metabolites; the taxonomic status of positive strains were analyzed by constructing 16S rRNA phylogenetic tree. RESULTS: We cloned and expressed the intact gene of human pancreatic alpha amylase successfully; the high-throughput screening model of alpha-amylase inhibitors was established; nearly 2000 actinomycete' metabolites were screened, 14 alpha-amylase inhibitor producing strains were obtained finally, and showed taxonomically rich diversity. CONCLUSION: The alpha-amylase inhibitor high throughput screening model had high practical value for developing new hypoglycemic drugs. PMID- 22097777 TI - [Comparison of three protein extraction methods for proteomic analysis of Alexandrium tamarense with two-dimensional electrophoresis]. AB - OBJECTIVE: In order to find the best extraction method for proteins of Alexandrium tamarense for two-dimensional electrophoresis (2-DE) analysis. METHODS: Three methods for extracting proteins from A. tamarense were compared, including trihydroxymethyl aminomethane (Tris-HCl ) buffer extraction, trichloroacetic acid (TCA)/acetone precipitation and lysis buffer extraction. Alga was cultivated in normal f/2 media (control) and supplemented with algicidal substances. Proteins obtained using the best extraction method were separated with 2-DE. Protein-expression differences were identified using matrix-assisted laser desorption/ionization-time of flight ( MALDI-TOF) mass spectrometry (MS). RESULTS: Among the three protein extraction methods, lysis buffer extraction shows the best detection of the number and quality of protein spots with a clear background. Then, the lysis buffer extraction method was successfully applied to profiling protein expression in algicidal substances stress conditions and 14 differential expression proteins were identified using MALDI-TOF/MS. CONCLUSION: Lysis buffer extraction was the most effective protein extraction method for Alexandrium tamarense. PMID- 22097779 TI - [Isolation and identification of a Bacillus amyloliquefaciens YB-3 against Rhizoctonia solani]. AB - OBJECTIVE: An antagonistic bacterial strain YB-3 against Rhizoctonia solani was isolated from soils. METHODS: Antagonistic strains were isolated by a reporter strain method. YB-3 was identified based on morphology observation, physiological and biochemical characterizations, Biolog, G + C content and 16S rDNA sequence analysis. The antagonistic spectrum and the properties of the inhibitor produced by Bacillus amyloliquefaciens YB-3 against plant pathogenic fungi and bacteria were investigated by means of plate two-way cultivation and disc diffusion method. RESULTS: The strain YB-3 against Rhizoctonia solani was identified as Bacillus amyloliquefaciens. The antagonistic results showed that it had distinctively inhibitive effects on 14 pathogenic fungi and 7 bacteria. In addition, it also had inhibitive effects on strains from genus Bacillus to which YB-3 belongs. Antagonistic properties of B. amyloliquefaciens YB-3 was thermostable, acid resistant, and protease sensitive. CONCLUSION: Bacillus amyloliquefaciens YB-3 was isolated and characterized which had distinctively inhibitive effects on Rhizoctonia solani and had broad-spectrum, highly efficient to plant pathogens. PMID- 22097780 TI - [Application of molecularly imprinted solid-phase extraction on drug residues in animal source foods]. AB - Due to the superior molecular recognition and good physical and chemical stability, the molecularly imprinted materials have gained more and more concern recently in extrication and separation fields. Using the imprinted materials as adsorbents, the molecularly imprinted solid-phase extraction (MISPE) allows selective extraction of the target molecules and its analogues from complex matrices, and is suitable for complex sample preparation and enrichment processes. This article describes the principle, latest progresses and parameters of molecularly imprinted solid-phase extraction and summarizes its extraction and applications for the determination of drug residues of animal source foods in recent years. Moreover, the shortcomings and future prospects of molecularly imprinted solid-phase extraction are also mentioned. PMID- 22097778 TI - [Establishment and evaluation of a real-time IAC-PCR for the detection of Salmonella]. AB - OBJECTIVE: The aim of this study was to establish a new EvaGreen real-time IAC PCR for the rapid detection of Salmonella. METHODS: We used Salmonella genomic comparison analysis to mine Salmonella-specific targets, and Primer Premier 5.0 to design primers which were evaluated by specificity and sensitivity tests. RESULTS: We obtained a Salmonella-specific gene that encodes putative type III secretion protein (ssaQ), and specific primers (SsaQ6L/SsaQ6R) were designed based on this gene. Then we established IAC-PCR and EvaGreen real-time IAC-PCR assays, which showed 100% inclusivity and 100% exclusivity on all strains tested. Their detection limits of purified Salmonella genomic DNA were 14.9 copies/PCR and 2.76 copies/PCR respectively. Artificial contamination assays showed that Salmonella could be detected after 10 hours and 8 hours enrichment when the original bacterial concentration was 4.2 cfu/10 mL. CONCLUSION: A new EvaGreen real-time IAC-PCR with high specificity and sensitivity was successfully developed for the rapid detection of Salmonella. PMID- 22097781 TI - [Development of rapid detection techniques for food safety]. AB - In recent years, food safety incidents are increasing due to the environmental pollution, abuse of additives, improper storage and so on. Rapid detection techniques are fast, simple and efficient for the requirements of preliminary screening to food security. In this paper, the rapid detection methods for food safety, including enzyme inhibition, biosensors and immunoassay, are reviewed, and the prospects of the future developments are expected. PMID- 22097782 TI - A perspective on high throughput analysis of pesticide residues in foods. AB - The screening of pesticide residues plays a vital role in food safety. Applications of high throughput analytical procedures are desirable for screening a large number of pesticides and food samples in a time-efficient and cost effective manner. This review discusses how sample throughput of pesticide analysis could be improved with an emphasis on sample preparation, instrumentation and data analysis. PMID- 22097784 TI - [Developments for the analysis of trans fatty acids in food products]. AB - More attention has been paid to trans fatty acids (TFAs) because of its influence on the human health. Adequate analytical tools are required for determining the contents of TFAs in labeling food products. Several different analytical methods such as spectrometry, chromatography, mass spectrometry and electrophoresis have been developed for analyzing TFAs in food products. This paper reviews the analytical methods developed for identifying and quantifying TFAs in oils and fats, describes the related merits of these approaches and their applications in food analysis. PMID- 22097783 TI - [Application of gene detection technology in food species identification]. AB - It is critical to determine the biological identity of all ingredients in food to ensure its safety and quality. Modern gene detection technology makes species identification in food more accurate, sensitive and rapid. A comprehensive review on its current applications in the last decade and the future perspective in food species identification is presented, including a brief introduction of gene detection methods, and their applications in plant-originated food, animal originated food, high value-added food and highly processed food. PMID- 22097785 TI - [Recent applications of solid-phase extraction techniques for analysis of trace residues and contaminants in food]. AB - The determination of trace residues and contaminants in food often requires extensive sample extraction and preparation prior to instrumental analysis. Due to the multiplicity and complexity of food matrices, it is not possible to use only one sample preparation technique. This review introduces the application of some new techniques of solid-phase extraction (SPE) in recent years, such as solid-phase microextraction (SPME), stir-bar sorptive extraction (SBSE), matrix solid-phase dispersion (MSPD), molecularly imprinted solid-phase extraction (MISPE) , immunoaffinity-based solid-phase extraction (IASPE), monolithic solid phase extraction, carbon nanotube solid-phase extraction, in the analysis of trace residues and contaminants in food. At last, future developments in this field are outlined. PMID- 22097786 TI - [Determination of five aflatoxins in Chinese patent medicines and medicinal herbs by immunoaffinity extraction coupled with ultra-high performance liquid chromatography-tandem mass spectrometry]. AB - A method for the determination of five aflatoxins (B1 , B2, G1 , G2, M1 ) in Chinese patent medicines and medicinal herbs by immunoaffinity extraction coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC MS/MS) was developed. The samples were extracted with 80% (v/v) methanol-water solution, followed by stepwise purification using an immunoaffinity column. The target compounds were then eluted with methanol. The extract was filtered then analyzed. With the gradient elution using a binary mobile phase containing of 0.1% formic acid-5 mmol/L ammonium acetate solution and methanol, the five aflatoxins were separated on an UHPLC BEH C18 column, followed by positive electrospray ionization and multi-reaction monitoring (MRM) provided by a triple quadrupole tandem mass spectrometer. The limits of detection for the standard solution of aflatoxins ranged from 0.05-0.3 microg/L. The linear response was observed in the spiked concentration range of 0.5-100 microg/L with the correlation coefficients higher than 0.99. The spiked recoveries were within 62.3%-82.4% at the spiked levels of 1.0 microg/kg and 5.0 microg/kg for all the five aflatoxins with the relative standard deviations (RSDs) below 10% (n = 6). The developed method is sensitive, accurate, and reproducible with the reasonable recoveries, and can be applied to the determination of the 5 aflatoxins in the Chinese traditional patent medicines, medicinal herbs as well as other similar complex matrices. PMID- 22097787 TI - [Determination of 61 organophosphorous pesticide residues in fruits, vegetables, milk, vegetable oils and animal muscles by dispersive solid-phase extraction and ultra performance liquid chromatography-tandem mass spectrometry]. AB - A dispersive solid-phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of 61 organophosphorous pesticide residues in fruits, vegetables, milk, vegetable oils and animal muscles. The fruit, vegetable and milk samples were extracted with acetonitrile and separated with salting out method; vegetable oil samples were dissolved by n-hexane, and extracted with acetonitrile; animal muscle samples were extracted with acetonitrile-water assisted by n-hexane and separated with salting out method. And then the supernatants were purified using dispersive solid-phase extraction (C18 and primary secondary amine powder) prior to the UPLC-MS/MS analysis. The analytes were indentified in positive electrospray ionization (ESI+) and multiple reaction monitoring (MRM) mode. The matrix-matched external standard calibration curves were used for quantitative analysis. Under the optimal conditions, the detection limits (S/N > or = 10) of the method were 0.01 mg/kg. The recoveries were 62.8%-107%, and the relative standard deviations (RSDs) were in the range of 4.2%-19%. The method has the advantages of easy, fast, and more sensitive, and can meet the requirement of the determination of organophosphorous pesticide residues in the foods. PMID- 22097788 TI - [Stir rod sorptive extraction with poly(methacrylic acid-co-ethylene dimethacrylate) as coating and its application to the analysis of sulfonamides in milk samples]. AB - A poly(methacrylic acid-co-ethylene dimethacrylate) polymer(poly(MAA-co-EDMA)) was prepared via in-situ polymerization on the outside surface of vial glass insert and used as stir rod sorptive extraction (SRSE) coating. The extraction performance of the polymer coating toward four sulfonamides (SAs) was investigated. The effects of several parameters to SRSE, such as the pH value, inorganic salt and organic phase concentrations of the sample matrix, were investigated. It demonstrated that the sulfonamides were captured on the poly(MAA co-EDMA) coating mainly through cation-exchange and hydrophobic interactions. A novel approach is presented for the determination of four sulfonamide antibacterial residues in milk samples by coupling SRSE to liquid chromatography and electrospray ionization mass spectrometry (SRSE/LC-ESI-MS). In this method, the detection limits (S/N = 3) of 0.11-0.52 microg/L and quantification limits (S/N = 10) of 0.35-1.72 microg/L were obtained. The method showed good linearity in the range of 1-500 microg/L. Good method reproducibility was also found by intra- and inter-day precisions, yielding the relative standard deviations (RSDs) less than 11.3%. The results demonstrated that the proposed method is simple, sensitive, low cost and suitable for the determination of sulfonamides in milk samples. PMID- 22097789 TI - [Screening method for 29 forbidden or limited synthetic pigments in cheese by liquid chromatography/quadrupole time-of-flight mass spectrometry]. AB - A screening method for 29 forbidden or limited synthetic pigments in cheese samples was established by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOF MS). The pigments were extracted by n-hexane/water (3:1, v/v). After extraction, the n-hexane extract, water extract and residue, were obtained. The n-hexane extract was then cleaned-up by gel permeation chromatography (GPC). The water extract was extracted by acetonitrile, and the residue by ammonia water/methanol (1:99, v/v). The results showed that the 29 synthetic pigments with a wide range of polarities were extracted effectively with the recoveries between 70% and 95%, and matched well by Q-TOF MS precision mass searching to the mass spectral library with matching scores between 59. 66 and 99. 47. The quantitative analysis of the 29 pigments was carried out by Target MS/MS. The limits of detection (LODs) for 8 Sudan dyes were 0.4-2.5 micro/kg while for 21 water-soluble synthetic pigments were 20-80 microg/kg. The screening method is suitable for a wide range of synthetic pigments, and can be applied to food samples with proteins and fat in matrix. PMID- 22097790 TI - [Determination of spinosyns A and D residues in food by high performance liquid chromatography-tandem mass spectrometry]. AB - A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS) method was established for the determination of spinosyns A and D residues in foodstuffs. The food samples were extracted with acetonitrile-water (50:50, v/v), and then purified by an HLB solid phase extraction (SPE) column. The analytes were determined by HPLC-MS/MS and quantified by external standard method. The mass spectrometric detection was operated with electrospray in positive ionization mode and the spinosyns A and D were identified in multiple reaction monitoring (MRM) mode. The linear range of the method was 1-20 microg/L, with the correlation coefficient (r2) of 0.999 9. No significant matrix effect was found for spiked samples. The recoveries of spinosyns A and D spiked in food were 76.2% 114.0% at the spiked levels of 1-10 microg/kg. The relative standard deviations (RSDs) were less than 10%. The limits of detection (LODs) and quantification (LOQs) were 0.2 microg/kg and 0.5 microg/kg for spinosyn A, 0.5 microg/kg and 1.0 microg/kg for spinosyn D, respectively. The proposed procedure was applied to the analysis of 969 real samples from Xiamen, Fujian Province (China), of which 15 positive samples were found. The results showed that the proposed method is sensitive and accurate for the determination of spinosyns A and D in foodstuffs. PMID- 22097791 TI - [Multi-residue determination of 289 pesticides in garlic by gas chromatography and gas chromatography/mass spectrometry]. AB - A new idea of solvent transfer technique was developed and applied to determine 283 pesticide residues in garlic by gas chromatography-mass spectrometry (GC-MS) (method I), and the other method using normal phase silica/selective elution technique was applied to determine 6 pesticide residues with strongly polar in garlic by gas chromatography (method II). For the method I, the residues were extracted from homogenized tissue with acetonitrile-water, separated with liquid liquid partition; the clear supernatant was purified by solvent transfer technique and solid phase extraction (Envi-18 and LC-NH2 columns), then was analyzed by GC-MS. For the method II, the residues were extracted from homogenized tissue using ethyl acetate and sodium sulfate assisted by ultrasonication. The supernatant was purified by solid phase extraction (primary secondary amine (PSA) powder and LC-Si column) prior to GC analysis. The determination was performed by using selected ion monitoring (SIM) mode in GC-MS method and flame photometric detector (FPD) in GC method, then external standard method was used in the quantification. Under the optimal conditions, the detection limits for the two methods (S/N > or = 10) of pesticides were 0.01-0.05 mg/kg, the recoveries carried out by the addition of standards of 0.01-0.20 mg/kg were 52%-163%, among which the recoveries for 88% pesticides were between 70% and 120%; the recoveries of the method II were 70%-111%; while the relative standard deviations were 2.4%-18% and 3.2%-9.3%, respectively. The model of solvent transfer technique and the sensitivity improvement of GC-MS was also studied. The methods are easy, fast, more sensitive, and can meet the requirement of the multiresidual analysis in garlic. PMID- 22097792 TI - [Determination of fipronil and its metabolites in tea by solid-phase microextraction coupled with gas chromatography and gas chromatography-mass spectrometry]. AB - An effective multi-residue method for the trace analysis of fipronil and four metabolites (fipronil-desulfinyl, fipronil-sulfide, fipronil-sulfone and fipronil carboxamide) in tea was developed based on solid-phase microextraction coupled with gas chromatography (SPME-GC). The targets were extracted with a fused-silica fiber coated with 85 microm polyacrylate (PA). The extraction was performed in a pH 9 buffer (containing 0.1 mol/L boracic acid, 0.1 mol/L KCI and 0.1 mol/L NaOH) at 60 degrees C and under 2500 r/min for 30 min. With the concentration range of 2-10 microg/kg, the recoveries ranged from 71.2% to 109.3% and the relative standard deviations (RSDs) were lower than 10% (n = 6). The limits of detection (LODs) and limits of quantitation (LOQs) of the studied compounds ranged from 0.3 microg/kg to 1.2 microg/kg and 1.0 microg/kg to 4.0 microg/kg, respectively, with the values well below the residue limits set by Japan, European Union and China. By the proposed method, 1 positive samples of 30 tea samples were found with fipronil and fipronil-sulfone. The identification of the method was done by gas chromatography-mass spectrometry (GC-MS). The method can be applied as a monitoring tool for tea, in the investigation of food to fipronil and its metabolites. PMID- 22097793 TI - [Determination of iodine and its species in plant samples using ion chromatography-inductively coupled plasma mass spectrometry]. AB - A method was established for the determination of iodine and its species in plant samples using ion chromatography-inductively coupled plasma mass spectrometry (IC ICP/ MS). Alkaline extraction and IC-ICP/MS were applied as the sample pre treatment method and the detection technique respectively, for iodate and iodide determination. Moreover, high-temperature pyrolysis absorption was adopted as the pre-treatment method for total iodine analysis, which finally converted all the iodine species into iodide and measured the iodide by IC-ICP/MS. The recoveries of iodine for alkaline extraction and high-temperature pyrolysis absorption were 89.6%-97.5% and 95.2%-111.2%, respectively. The results were satisfactory. The detection limit of iodine was 0.010 mg/kg. The iodine and its speciation contents in several kinds of plant samples such as seaweeds, kelp, cabbage, tea leaf and spinach were investigated. It was shown that the iodine in seaweeds mainly existed as organic iodine; while the ones in kelp, cabbage, tea leaf and spinach mainly existed as inorganic iodine. PMID- 22097794 TI - [Improvement of the method for methylmercury determination in aquatic products using liquid chromatography online coupled with atomic fluorescence spectrometry]. AB - The improvement method was developed for methylmercury determination using liquid chromatography online coupled with cold vapor atomic fluorescence spectrometry (LC-CV-AFS). Cysteine was used as complexing agent in mobile phase instead of mercaptoethanol. Under the optimized conditions, baseline separation of mercury species could be achieved within 8 min on a C18 column with a mobile phase of 5% (v/v) acetonitrile-1 g/L L-cysteine-50 mmol/L ammonium acetate aqueous solution. The linear range of calibration curve of methylmercury was 1-50 microg/L and the limit of detection (S/N = 3) for methylmercury was 0.3 microg/L. Ultrasonication assisted hydrochloric acid extraction was used to extract methylmercury from seafood samples. The sample extract was cleaned up by a C18 solid phase extraction (SPE) cartridge. For validation of the method, certified reference materials and spiked seafood samples were analyzed. The determined methylmercury contents of certified reference materials NIST1566b, BCR464 and GBW10029 agreed well with the certified values. The determined methylmercury values for Food Analysis Performance Assessment Scheme (FAPAS) sample 07115 were satisfied. The recoveries of methylmercury in seafood samples at three spiked levels (10, 50 and 500 microg/kg) ranged from 89% to 112%, including cooked seafood food. The precision of the method based on relative standard deviation (RSD) was not more than 7%. The present method of LC-CV-AFS is accurate, sensitive, simple, and can meet the demand of methylmercury determination in seafood. PMID- 22097796 TI - [Species identification of grouper and snapper in Taiwan Strait using polymerase chain reaction-restriction fragment length polymorphism analysis and lab-on-a chip system]. AB - Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and lab-on-a-chip system were used to identify grouper and snapper species in Taiwan Strait. A fragment of 464 bp length of mitochondrial cytochrome b gene was amplified by PCR and the products were digested with restriction enzymes Dde I , Hae III and NLa III, individually. The fragments generated after digestion were further resolved on the DNA Chip. Eight grouper species and five snapper species were successfully identified. The results demonstrated that PCR RFLP analysis and lab-on-a-chip system provide a fast, easy, automated, and reliable analysis approach. This approach is potential for the purpose of fish adulteration control. PMID- 22097795 TI - [Application of polymerase chain reaction-restriction fragment length polymorphism and lab-on-a-chip technology to the identification of fish species from Bohai Bay]. AB - Nine representative fish species from Bohai Bay were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and lab-on-a chip technology. The nine fish species were Pseudosciaena polyactis, Lateolabrax japonicus, Scomberomorus niphonius, Pneumatophorus japonicus, Pseudopleuronectes yokohamae, Collichthys lucidus, Sebastes schlegeli, Cleisthenes herzensteini and Saurida elongata. The 464 bp fragment of mitochondrial cytochrome b gene was amplified and further digested by Dde I , Hae III and Nla III. The digested DNA fragments were analyzed by microfluidic capillary electrophoresis. The nine fish species were fully discriminated. The results demonstrated that the proposed method is efficient, precise and fast in fish species identification. PMID- 22097797 TI - [In situ and rapid identification of tea by direct analysis in real time mass spectrometry]. AB - By applying an ambient mass spectrometric method--direct analysis in real time mass spectrometry (DART MS), a method was developed for rapid identification of the principal constituents in different kinds of tea. The identification of different kinds of tea was also achieved by characteristic mass spectrometric signals. Under atmospheric pressure, DART MS method does not require any sample preparation, greatly reduces the analysis time, realizes the in situ, rapid, accurate, and high-throughput analysis. PMID- 22097799 TI - [Preparation of natural matrix standard sample of minced eel for quality control of flumequine residue]. AB - In order to obtain quality control samples for the analysis of flumequine residue in eel which are consistent with real detection samples, minced eel was prepared as natural matrix standard samples containing flumequine. The results showed that through the administration of drug application and appropriate time of sample acquisition, the natural positive matrix containing the expected levels (5-10 microg/kg) of flumequine and the representative of actual samples at the original state could be obtained. The uniformity of the material was ensured by homogenizing and paddle type blending. The irradiation of Co60-gamma rays at 12 kGy and the packaging material could prevent the degradation of the minced samples at ambient temperature and facilitate the inter-laboratory transfer in any season. PMID- 22097800 TI - [Progress in co-culture and differentiation in adipose-derived stem cells: a review]. AB - Stem cells can be differentiated into many kinds of somatic cells under defined culture conditions. In addition, the homing possess can be partially imitated by co-culture of stem cells with mature somatic cells. Regarding the importance of clinical application of adipose-derived stem cells (ADSCs), our review first introduced the sources and signs of ADSCs, and then the current knowledge of ADSCs co-culture technology, including drug and chemical induced culture, two dimensional (2D) and three-dimensional (3D) co-culture, mechanisms of ADSCs differentiation, and application development in recent years in details. Finally, we also addressed prospects of ADSCs. PMID- 22097798 TI - [Rapid analysis of melamine in milk and milk powder using QuEChERS approach coupled with weak cation exchange chromatography]. AB - A simple, rapid method for the determination of melamine in milk and milk powder was developed using QuEChERS approach coupled with weak cation exchange chromatography (WCX). The samples were extracted and cleaned-up by medicinal alcohol and lipid adsorbent (LAS) simultaneously, then centrifuged and filtered for high performance liquid chromatographic (HPLC) analysis. The separation was performed on a WCX column (150 mm x 4.6 mm, 5 microm) with 2 mmol/L KH2 PO4 (pH 3.8) as mobile phase. The flow rate was 1.5 mL/min and the detection wavelength was 208 nm. The injection volume was 20 microL and the column temperature was 30 degrees C. Under the optimized conditions, good linearity was obtained in the range of 0.02-20 mg/L with a correlation coefficient (r2) of 0.999 9. For samples spiked with melamine standard in the range of 1-50 mg/kg, the average recoveries of standard in the milk and milk powder were 98.9%-105.2% and 86.4%-102.9%, respectively. The relative standard deviations were 0.9%-3.4% and 1.5%-6.7%, respectively. The limits of detection (LOD, S/N > or = 3) were 0.05 mg/kg (milk) and 0.1 mg/kg (milk powder). The present method is green due to not use of the toxic organic solvents. PMID- 22097801 TI - [Molecular recognition code between pathogenic bacterial TAL-effectors and host target genes: a review]. AB - As the pathogenic bacterial virulence and avirulence factors, transcription activator like (TAL) effectors of Xanthomonas can resulted in the host diseases or resistance responses. TAL effectors can specifically bind the target DNA of host plant with a novel protein-DNA binding pattern in which two amino acids recognize one nucleotide. The complexities of TAL-DNA binding have the feasibility in use of gene therapy through homologous recombination and site specific mutation. By using the molecular recognition code between TAL-effectors and host target genes, we can exploit both the susceptible and resistance genes; broad spectrum resistance induced by multiple TAL effectors could also be manipulated. Deeper insight in the area of protein-DNA binding mechanism will benefit the application in the biomedical engineering and agricultural engineering. This article reviews the findings and functions of TAL effectors, the binding specificity and recognition code between TAL-effectors and host target genes. The possible applications and future prospects of the molecular recognition code have been discussed. PMID- 22097802 TI - [Epigenetic regulation of secondary metabolite biosynthesis in filamentous fungi: a review]. AB - Secondary metabolites of filamentous fungi are important sources of new drugs, and their biosynthetic processes are regulated by numerous factors. Recent studies indicate that many filamentous fungal secondary metabolites are regulated by epigenetic modifications, which not only affect the titers of secondary metabolites, but also activate the cryptic gene clusters. This review summarizes recent advances of epigenetic application in filamentous fungal secondary metabolite biosynthesis, especially the types of fungal epigenetic modification and epigenetic remodeling of the fungal secondary metabolism. The application of epigenetic theory in filamentous fungi is becoming a new strategy for fungal strain improvement and a powerful method to obtain novel natural products. PMID- 22097803 TI - [Development of SPA-ELISA for detection of antibodies against rabies virus based on expression of main antigenic determinant of nucleoprotein]. AB - To evaluate the effectiveness of rabies vaccination, we developed the SPA-ELISA method to detect the antibodies against rabies virus (RV) using the main antigenic determinant of nucleoprotein (RV N1) as antigen. The complete Nucleoprotein (N) gene and the partial N1 gene (1 000-1 353 bp) of RV Flury LEP strain were amplified using RT-PCR and PCR approaches. The two fragments were inserted into pGEX-6P-1 respectively. Then we transformed the recombinant plasmids into Escherichia coli BL21(DE3) strain and expressed them by adding 1 mmol/L of IPTG (isopropyl-beta-D-thiogalactopyranoside). SDS-PAGE analysis showed that both of the two recombinant proteins were presented as inclusion bodies. Compared with the complete nucleoprotein, the partial protein (RV N1) was expressed at a much higher level in E. coli BL21(DE3). The antigenic specificity of the partial N1 protein was confirmed by Western blotting. By coating the plates with purified RV N1 as an antigen, an SPA-ELISA method for the detection of the antibodies against RV was established. By optimizing this method, the optimal concentration of RV N1 coating the ELISA plate was 2 mg/L. The optimal concentration of serum samples and SPA-HRP was 1:100 and 1:4 000 respectively. Compared with a commercially available ELISA kit coating RV as antigen, the coincidence rate of SPA-ELISA was 94.1%. Our results show that the developed SPA ELISA based on the RV N1 was useful for the detection of the antibodies against RV in the sera of dogs. PMID- 22097804 TI - [Optimization of plant des-pGlu1-Brazzein gene according to yeasty biased codons and its expression in Pichia pastoris]. AB - According to the amino acid sequence of des-pGlu1-Brazzein, 4 pairs of oligonucleotide with cosmic site were synthesized by using yeasty biased codons. After linkage and PCR, the 179 bp code area of des-pGlu1-Brazzein was obtained and inserted into pPIC9K, which resulted in the recombinant expression vector pPIC9K-Bra. By digestion with Sal I, the lined pPIC9K-Bra was transformed into Pichia pastoris GS115 by electric shock. The results of expression indicted that the secreted target protein accounted for 51.6% of total protein in the supernatant and showed biological activity after purification. PMID- 22097805 TI - [Construction of a bivalent plant expression vector carrying VvSUC11 and VvSUC12 genes and its genetic transformation in sugar beet]. AB - We have recombined genes VvSUC11, VvSUC12 from Vitis vinifera L., and root specific promoters of sweet potato storage protein gene from Ipomoea batatas L. Lam., named as SP1 and SP2. We have constructed a vector pCAMBIA2301-SP1- VvSUC11 SP2-VvSUC12 using pCAMBIA2301 as an original vector. VvSUC11 and VvSUC12 were under the control of root-specific promoters of sweet potato storage protein gene. We transformed the vector into KWS-9103 breeding line of Beta vulgaris L. with Agrobacterium-mediated transformation. We have established the optimal genetic transformation protocol of sugar beet as following: the explants pre cultured for 4 days were immersed in Agrobacterium suspension of OD(600)=0.5, supplemented with 0.005% Silwet L-77, and followed by a 4-day culture on medium containing cefotaxime, then the buds were selected on medium containing kanamycin and cefotaxime. The percentage of kanamycin-resistant buds was as high as 42%. Results of PCR and RT-PCR proved that the target genes had integrated into sugar beet genome and expressed. It will lay a foundation for further studying their function in Beta vulgaris. PMID- 22097806 TI - [Role of cytoglobin in protecting hepatic stellate cells against oxidation induced damage]. AB - The aim of this study was to reveal the protection role and the related mechanism of cytoglobin on the oxidation induced hepatic stellate cell damage. We applied siRNA to interfere the endogenous cytoglobin gene, used recombinant cytoglobin protein to treat the completely activated human hepatic stellate cell line LX-2 and the incompletely activated primary rat hepatic stellate cells, or over expressed cytoglobin protein in LX-2 cells. We used two different oxidative stress related models, the hydrogen peroxide model and the iron-overload model in our experiments and investigated the proliferation status and the intracellular superoxide level of the cells. The results showed that endogenous cytoglobin exerted significant protective effects on hydrogen peroxide or iron-overload induced LX-2 cell damage, confirming that upregulation of cytoglobin was the protective response of activated hepatic stellate cells to oxidative stress. Recombinant cytoglobin protein could protect LX-2 cells from oxidation induced damage, and prevent primary rat hepatic stellate cells from excessive proliferation and injury. The cytoplasmic reactive oxygen species (ROS) scavenging capacity of the recombinant cytoglobin protein was not as good as its capacity in scavenging ROS outside the cells, likely owing to the lack of active transporting mechanisms. Intracellular over-expression of cytoglobin protein could exert significant protective effect on LX-2 cells treated with hydrogen peroxide or iron-overload. Our results would accelerate the exploitation of new anti-fibrotic targets. PMID- 22097807 TI - [Antigen selection, optimized expression and polyclonal antibody preparation of O GlcNAcase]. AB - In order to probe the biological function of O-GlcNAc and the pathogenesis of associated diseases, it is essential to prepare a potent and specific O-GlcNAcase (OGA) antibody. Based on protein sequence analysis, we found N terminal 1-350 amino acids of OGA (sOGA) has high antigenicity and hydrophilicity and then constructed it into plasmid pET28a vector. First, we optimized the expression of sOGA in Escherichia coli BL21(DE3) (0.05 mmol/L IPTG, 10 hours) and purified it with the Ni-NTA affinity chromatography and size exclusion chromatography respectively. SDS-PAGE verified the molecular weight (45 kDa) and the purity (>95%) of sOGA and the purified protein was subjected to immunize New Zealand rabbits. Finally, we obtained OGA polyclonal antibody by affinity purifying the antiserum with CNBr-activated Sepharose 4B beads. Western blotting and ELISA assay showed that this antibody could recognize three OGA isoforms with high specificity and the sensitivity was 0.11 ng/mL (the titer was 1:80 000). These results indicated the prepared polyclonal antibody of OGA can be used for the biological function study of OGA. PMID- 22097808 TI - [Design and expression of an inhibitor for HIV-1 targeting dendritic cell]. AB - Human immunodeficiency virus (HIV) infects the host cells by the fusion of viral and cell membranes. Blocking the combining between HIV and the receptors can prevent HIV from entering the host cells. We designed an invasion-inhibitor for HIV-1 targeting dendritic cell (DC), including 2 important HIV-1 receptors CD4 and CCR5, and 2 molecules Flt3-L and Mip-3alpha. With the synthetic gene of the inhibitor, 2 eukaryotic expression vectors pABK-CKR5-CD4/Flt3L-Mip3alpha (pABK HIV-MF) and pABK-CKR5-CD4 (pABK-HIV-MT) were constructed and transfected into HEK 293 cells for expression. Results from RT-PCR, immunofluorescent assay, ELISA and Western blot approved that the invasion-inhibitor for HIV-1 was successfully and exactly expressed in the eukaryotic cells. Current study formed a solid base for the further research on the function of inhibitors for HIV-1 and elimination targeting DC. PMID- 22097809 TI - [Analysis of the transcriptional profiling of cell cycle regulatory networks of recombinant Chinese hamster ovary cells in batch and fed-batch cultures]. AB - In the light of Chinese hamster ovary (CHO) cell line 11G-S expressing human recombinant pro-urokinase, the differences of gene expression levels of the cells in different growth phases in both batch and fed-batch cultures were revealed by using gene chip technology. Then, based on the known cell cycle regulatory networks, the transcriptional profiling of the cell cycle regulatory networks of the cells in batch and fed-batch cultures was analyzed by using Genmapp software. Among the approximate 19 191 target genes in gene chip, the number of down regulated genes was more than those of up-regulated genes of the cells in both batch and fed-batch cultures. The number of down-regulated genes of the cells in the recession phase in fed-batch culture was much more than that of the cells in batch culture. Comparative transcriptional analysis of the key cell cycle regulatory genes of the cells in both culture modes indicated that the cell proliferation and cell viability of the cells in both batch and fed-batch cultures were mainly regulated through down-regulating Cdk6, Cdk2, Cdc2a, Ccne1, Ccne2 genes of CDKs, Cyclin and CKI family and up-regulating Smad4 gene. PMID- 22097810 TI - [Differentiation of porcine amniotic fluid stem cells into the beating cardiomyocytes]. AB - The aim of this research is to find an effective cardiomyocyte-induced method derived from porcine amniotic fluid stem cells (pAFS). For cardiac differentiation, the cells were formed embryoid bodies (EBs) firstly, then cultured in induced-medium including 5-azacytidine (5-aza) and vitamin C (Vc). We detected the specific markers of cardiomyocyte by immunocytochemistry, RT-PCR and transmission electron microscope. The results showed that some embryoid bodies beat rhythmically after 10 days of induction. Furthermore, analysis of t test revealed that the percentage of beating cardiomyocyte-like cell clusters was highest (33%) when induction using 0.1 mmol/L Vc and 5 micromol/L 5-aza. Immunocytochemistry analysis demonstrated that cardiomyocyte-like cell clusters expressed alpha-actin, Tnni3. RT-PCR analysis also illustrated that TbX5, Gata4, alpha-MHC and Tnni3 were expressed positive in cardiomyocyte-like cell clusters. Especially, we observed basic structures of myocardium, such as myofilament, glycogen granule and so on by transmission electron microscope. In conclusion, 5 azacytidine and vitamin C could promote differentiation of pAFS into myocardium. PMID- 22097811 TI - [Construction and expression characterization of transgenic chicken bioreactor vector]. AB - We constructed transgenic chicken bioreactor vector, driven by chicken ovalbumin promoter, lentiviral vector and cytomegalovirus (CMV) promoter control vector encoding green fluorescent protein (GFP) and luciferase (Luc) as reporter genes. The three vectors were used to transfect or infect chicken primary oviduct epithelial cells, embryo fibroblasts cells, mouse 3T3-L1 preadipocytes cells and bovine mammary epithelial cells. High efficient and specific expression vector for transgenic chicken bioreactor was determined by detecting fluorescence and luciferase activity. Reporter gene analysis showed that chicken ovalbumin promoter expression vector was not cell type-specific in these four different cells. Additionally, luciferase reporter analysis illustrated that the chicken ovalbumin promoter activity was over 100 times lower than that of the CMV promoter in four different cells. Both of these two reporter genes were expressed in those four different cells infected by lentiviral expression vectors. Similarly, the GFP reached the similar expression level in cells infected by lentivirus and cells transfected with CMV promoter plasmid vectors when the multiplicity of infection was 20. In conclusion, the transgenic chicken bioreactor vector under the control of chicken ovalbumin promoter was not highly efficient and cell type-specific. However, the efficient expression and extensiveness oflentiviral vector could be used for studying chicken oviduct bioreactor. PMID- 22097812 TI - [Evaluation and application of exogenous gene expression system based on retroviral vector]. AB - Currently, exogenous gene expression system based on retroviral vector has been widely used as efficient gene expression system in both gene therapeutic research and RNA interference. In this study, we evaluated the efficiency of exogenous gene expression mediated by the retroviral vector in mammalian cells. First, we constructed EGFP (enhanced green fluorescent protein) vector using pcDNA3.1(+) and retroviral vector pQCXIN as backbone vector respectively. Then, we transfected or infected HEK293 cells and CHO-K1 cells with above vector or corresponding retroviral virus, and measured the relative fluorescence intensity (RFI) of EGFP. The results showed that the RFI of the retroviral virus-infected cells was two times higher than that of the plasmid-transfected cells. Further experiments revealed repeated virus infection enhanced the expression of EGFP markedly, with RFI increasing twice after four rounds of virus infection. Furthermore, the EGFP expression in HEK293 cells mediated by the retroviral vector was more stable than transfected with plasmid pcDNA3.1(+). Finally, we further validated the efficiency of exogenous gene expression system based on the retroviral vector by expressing recombinant human activated protein C (rhAPC) in HEK293 cells. We obtained HEK293 cell lines with rhAPC expression between 10 and 15 microg/(10(6) cells d). In conclusion, the exogenous gene expression system based on the retroviral vector is an alternative method for the generation of stable and high-expressing mammalian cell lines. PMID- 22097813 TI - [Establishment of loop-mediated isothermal amplification technique for rapid detection of NDM-1 gene]. AB - We established a rapid detection method of New Delhi Metallo-beta-Lactamase Gene (NDM-1) based on Loop-mediated Isothermal Amplification (LAMP). With the application of LAMP, we designed four sets of LAMP premiers, using NDM-1 gene as the target sequence, and selected the set of optimal primers. Meanwhile, we established optimal reaction systems and conditions to carry out the sensitivity and specificity experiments. The experiment results showed that the whole detection process took only one hour and could be observed visually. In the experiment of sensitivity, NDM-1 gene had a detection limit of 6 copies in each reaction. In the experiment of specificity, we detected NDM-1 gene in 4 pathogen strains (Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae), and the total DNA from intestinal microbes and the total DNA from soil microbes. We had not detected the amplification reactions. The detection method established could rapidly detect NDM-1 gene and visualize the experiment result. The method is easy to operate and has high sensitivity and specificity and thus has great application value in basic research laboratories, emergent detection and spot detection. PMID- 22097815 TI - [Expression, purification and characterization of non-specific Serratia nuclease in Escherichia coli]. AB - To efficiently produce non-specific nuclease (NU) of Serratia marcescens through recombinant overexpression approach and to characterize the purified NU. The nuclease gene was amplified from the genomic DNA of Serratia marcescens by PCR and fused into vector pMAL-c4X with maltose binding protein (MBP) tag. The recombinant vector verified by DNA sequencing was transformed into Escherichia coli BL21. The expressed MBP-NU was purified through the amylose resin and its catalytic characters were analyzed. The results showed the NU gene had 97% identities with the reported S. marcescens nuclease gene and intracellularly expressed in E. coli BL21. The optimal expression conditions were 37 degrees C, 0.75 mmol/L IPTG with 1.5 h induction. The purified MBP-NU exhibited non-specific nuclease activity, able to degrade various nucleic acids, including RNA, single stranded DNA and double-stranded DNA that was circular or linear. Its optimal temperature was 37 degrees C and optimal pH 8.0. From 1 L culture broth 10.8 mg NU could be purified with a specific activity of 1.11x10(6) U/mg. The catalytic activity of NU was not inhibited by reagents such as EDTA (0.5 mmol/L), PMSF (1 mmol/L) and KCl (150 mmol/L) commonly used in protein purification. PMID- 22097814 TI - [Rapid expression and preparation of the recombinant fusion protein sTNFRII-gAD by adenovirus vector system]. AB - We expressed and prepared the recombinant fusion protein sTNFRII-gAD consisted of soluble TNF receptor II and the globular domain of adiponectin by Adenovirus Vector System in mammalian BHK21c022 cells. First we used the adenovirus vector containing EGFP gene (rAd5-EGFP) to infect BHK21c022 cells at different MOI (from 0 to 1 000), and then evaluated their transduction efficiency and cytotoxicity. Similarly, we constructed the replication-deficient adenovirus type 5-sTNFRII-gAD (rAd5-sTNFRII-gAD). We collected the supernatants for Western blotting to determine the optimal MOI by comparing the expression levels of sTNFRII-gAD fusion protein, 48 h after the BHK21c022 cells were infected by rAd5-sTNFRII-gAD at different MOIs (from 0 to 1 000). Then, we chose rAd5-sTNFRII-gAD at MOI 100 to infect five bottles of BHK21c022 cells in 100 mL of serum-free chemically defined media 100 mL, harvested the supernatant every 48 h for 6 times, and condense and purify sTNFRII-gAD fusion protein by ammonium sulfate salt-out and size-exclusion chromatography, respectively. Finally, we analyzed anti-TNFalpha activity of sTNFRII-gAD fusion protein on L929 cells in vitro. The results showed that the number of BHK21c022 cells expressing EGFP protein was increased significantly with the increase of MOI. However, some cells died at MOI of 1 000 while there was no significant cytotoxicity at MOI from 0 to 100. Western blotting analysis showed that the more adenoviruses, the higher expression of sTNFRII-gAD fusion protein in the supernatant with the highest expression at MOI 1 000. We successfully obtained about 11 mg bioactive and purified sTNFRII-gAD fusion protein at last. The in vitro assay demonstrated that the sTNFRII-gAD fusion protein was potent to antagonize TNFalpha's cytotoxicity to L929 cells. Put together, we established a recombinant adenovirus vector/BHK21 cell expression system, characteristic of the efficient serum-free culture and easy scaling-up. PMID- 22097816 TI - [Advances in researches on hyperspectral remote sensing forestry information extracting technology]. AB - The hyperspectral remote sensing technology has become one of the leading technologies in forestry remote sensing domain. In the present review paper, the advances in researches on hyperspectral remote sensing technology in forestry information extraction both at home and abroad were reviewed, and the five main research aspects including the hyperspectral classification and recognition of forest tree species, the hyperspectral inversion and extraction of forest ecological physical parameters, the hyperspectral monitoring and diagnosis of forest nutrient element, the forest crown density information extraction and the hyperspectral monitoring of forest disasters were summarized. The unresolved problems of hyperspectral technology in the forestry remote sensing applications were pointed out and the possible ways to solve these problems were expounded. Finally, the application prospect of hyperspectral remote sensing technology in forestry was analyzed. PMID- 22097817 TI - [FTIR microspectroscopy and its progress in application]. AB - FTIR microspectroscopy technique was born in the mid-nineties. The research on this technique has just began abroad, and this technology has not yet been widely recognized in China. It is a rapid, nondestructive testing technology, has the advantages of microdomain, visualization, high precision and high sensitivity. In the present study, the composition, operational principle and working mode of FTIR microspectroscopy were summarized. The progress in application of FTIR microspectroscopy technique was investigated in some fields, including biomedicine, microbiology, forensic science, materials science, nutrition and feed science and agricultural products. The difficulty of FTIR microspectroscopy research and the prospects of this technique were also discussed. PMID- 22097818 TI - [Applications of surface-enhanced Raman spectroscopy to detection of polycyclic aromatic hydrocarbons]. AB - In the present review article, the methodology and recent advances of surface enhanced Raman scattering (SERS) were described in detection of polycyclic aromatic hydrocarbons (PAHs). PAHs, a series of organic compounds, are of much concern because some of them as pollutants have been identified as carcinogenic, mutagenic and teratogenic compounds. They show low affinity to metallic surface, which confines applications of SERS to their detections. This article reviewed the development trends in PAHs analysis by using of SERS substrate modified by supramolecular system. And perspective SERS in PAHs studies have also been presented. PMID- 22097819 TI - [Effects of Ag nanocrystals on electroluminescence in Si oxide films]. AB - Ag nanocrystal-embedded silicon oxide (SiO2 : Ag) films with varying Ag fractions were prepared on p-Si substrate by magnetron co-sputtering and thermal annealing. Visible electroluminescence (EL) was observed from the structures of ITO/SiO2 : Ag/p-Si. The authors found that Ag nanocrystals in the SiO2 film can not only shift the EL peak evidently but also enhance the EL intensity markedly. The larger the Ag fractions in the EL structures, the longer the peak wavelengths. The electromagnetic interactions of the Ag nanocrystals with the emitters in the film via local surface plasmons are considered responsible for these experimental results. PMID- 22097820 TI - [Luminescence characteristics of PVK doped with Ir(Fppy)3]. AB - In the present work, the photoluminescence (PL) and electroluminescence (EL) characteristics of Tris[2-(2,4-difluorophenyl)pyridine]iridium(III) (Ir(Fppy)3) doped poly(n-vinylcarbazole) (PVK) with different doping concentrations were investigated. And a blue phosphorescent organic light-emitting diode (OLED) with the structures of ITO/PEDOT : PSS/PVK : Ir(Fppy)3/BCP/Alq3/LiF/Al was fabricated. The experimental results show that the luminescence performances of devices are different as the doping concentration of Ir(Fppy)3 is different. When the doping concentration of Ir(Fppy)3 is lower, the luminescence of PVK can be found in EL spectra. When the doping concentration is too high, concentration quenching may occur. As the doping concentration is suitable, the luminescence of PVK can not be found, only the luminescence of Ir(Fppy)3 can be found in EL spectra. It is concluded that the device with doping concentration of 4% has the best photoelectric performance according to its current density-voltage-luminance curve. PMID- 22097821 TI - [Near-infrared luminescence and energy transfer of ACaPO4 : Eu2+, Nd3+ (A = Li, K, Na)]. AB - Near-infrared (NIR) luminescence phosphors ACaPO4 : Eu2+, Nd2+ (A = Li, K, Na) were prepared by conventional solid state method and the sensitization of Nd3+ near-infrared luminescence by Eu2+ was investigated. The characteristic NIR luminescence of Nd3+ in ACaPO4 matrix is greatly enhanced by co-doping of Eu2+. The fluorescence properties of ACaPO4 : Eu2+, the NIR luminescence properties of ACaPO4 : Eu2+, Nd3+ and the fluorescence lifetime were studied. The effect of emission wavelength of Eu2+ on NIR luminescence of Nd3+ was investigated; The energy transfer mechanism between Eu2+ and Nd3+ was also discussed. Emission peak wavelength of Eu2+ In ACaPO4 matrixes was found red shift with the series of A = Li, K, Na and the extent of the overlap with the different excitation peaks of Nd3+ changes obviously. It was concluded that the emission peak position of Eu2+ is a very important factor for energy transfer, and the optimal wavelength range for Eu2+ --> Nd3+ energy transfer is 500 to 550 nm. PMID- 22097822 TI - [The spectrogram characteristics of organic blue-emissive light-emitting excitated YAG : Ce phosphor]. AB - It is demonstrated that the panchromatic luminescence devices with organic blue emissive light-emitting was fabricated. This technique used down conversion, which was already popular in inorganic power LEDs to obtain white light emission. A blue OLED device with a configuration of ITO/2T-NATA (30 nm)/AND : TBPe (50 Wt%, 40 nm)/Alq3 (100 nm)/LiF(1 nm)/Al(100 nm) was prepared via vacuum deposition process, and then coated with YAG : Ce phosphor layers of different thicknesses to obtain a controllable and uniform shape while the CIE coordinates were fine tuned. This development not only decreased steps of technics and degree of difficulty, but also applied the mature technology of phosphor. The results showed that steady spectrogram was obtained in the devices with phosphor, with a best performance of a maximum luminance of 13 840 cd x m(-2) which was about 2 times of that of the devices without phosphor; a maximum current efficiency of 17.3 cd x A(-1) was increased more two times more than the devices without phosphor. The emission spectrum could be adjusted by varying the concentration and thickness of the phosphor layers. Absoulte spectrogram of devices was in direct proportion with different driving current corresponding. PMID- 22097823 TI - [Luminescence investigation of Na(z)Ca(1-x-2y-z)Bi(y)MoO4 : Eu(x+y)3+, red phosphors]. AB - A series of red phosphors with the composition Na(z)Ca(1-x-2y-z), Bi(y) MoO4 : Eu(x+y)3+ (y, z = 0, x = 0.24, 0.26, 0.30, 0.34, 0.38; x = 0.30, y = 0.01, 0.02, 0.03, 0.03, 0.05, 0.06, 0.07; x = 0.30, y = 0.04, z = 0.38) were prepared via traditional solid-state method. The crystal structures of the obtained phosphors were identified by X-ray powder diffraction (XRD) method. The photoluminescence properties of the samples were characterized by fluorescence spectrophotometer. The results indicated that the concentration of Eu3+ single doped Ca(1-x) MoO4 : Eu3+ with the maximum luminescence intensity was found to be 0.30 (namely, Ca0.70 MoO4 : Eu(0.30)3+); the photoluminescence properties with different ratio of Bi3+/Eu3+ codoped Ca0.70-2y Bi(y) MoO4 : Eu(0.30+y)3+, were also investigated, and the results showed that the charge band (CTB) reached the maximum value when the y value was equal to 0.03; for the characteristic excitation peaks of Eu3+, however, the intensity of the excitation spectral line locating at 393 nm was stronger than that at 464 nm when y < 0.03, while the intensity at 464 nm was greater than that at 393 nm when y > or = 0.03; the intensity of excitation peaks locating at 393 and 464 nm respectively both reached the maximum intensity when the y value was 0.04. The relative intensity of the excitation and emission of the above phosphor was enhanced greatly when Na2CO3 acting as charge compensation was added. The above results showed that the relative intensity between 393 and 464 nm could be changed by adjusting the ratio of Bi3+ /Eu3+ codoping concentrations. PMID- 22097824 TI - [Synthesis, characterization and luminescence properties of novel beta-diketone and Eu(III) ternary complex]. AB - The novel beta-diketone 1-(4-bromophenyl)-3-phenylpropane-1, 3-dione (L) was synthesized at room temperature by classical Claisen condensation reaction. With the beta-diketone L as the first ligand and phen as the secondary ligand, and a new rare-earth Eu (III) ternary complex was prepared. The ligand L and ternary complex were characterized by elemental analysis, IR spectra, UV spectra and fluorescence spectra. IR spectra indicated that: the novel ligand L contained the structure of beta-diketone, where the content of enol was high; the Eu3+ ion in the ternary complex was coordinated with six oxygen atoms of three L ligands and two nitrogen atoms of the second ligand phen. UV spectra showed that the main absorption was from the first ligand L in the Eu (III) ternary complex. The excitation and emission spectra of the ternary complex were measured and investigated. Fluorescence spectra demonstrated that the ternary complex could emit characteristic fluorescence of rare earth Eu3+ ion and the strongest emission band was narrow which was attributed to the 5 D0 --> 7 F2 transitions of the 4f electrons of the central Eu3+ ions. So, the new Eu(III) ternary complex is an excellent red-emitter which would be regarded as a valuable material with bright red fluorescence because it presents good monochromaticity. PMID- 22097825 TI - [Growth of codoped CdWO4 crystals by Bridgman method and their optical spectra]. AB - The CdWO4 crystals with good quality in the size of Phi25 mm x 120 mm, doped with Co in 0.5% molar fraction in the raw composition, were grown by the Bridgman method by taking -70 degrees C x cm(-1) of solid-liquid interface and -0.50 mm x h(-1) growth rate. The crystal presents transparence and deep blue. The X-ray diffraction (XRD) was used to characterize the crystals. Three absorption peaks at 518, 564 and 655 nm respectively, which are attributed to the overlapping of 4 T1 (4F) --> 4A2 (4F) and 4 T1 (4F) --> 4 T1 (4P) of Co2+ octahedrons, and a wide band centered at 1 863 nm, which is attributed to 4Ti (4F) --> 4 T2 (4F), was observed. The absorption results indicated that the Co ions presented +2 valence in crystal and located within the distorted oxygen octahedrons. The crystal-field parameter D(q) and the Racah parameter B were estimated to be 990 and 726.3 cm( 1) respectively based on the absorption spectra. A fluorescence emission at 778 nm (4T1 (4P) --> 4 T1 (4F)) for codoped CdWO4 crystals was observed under excitation by 520 nm light. It can be deduced from the changes in absorption and emission intensity of different parts of crystal that the concentration of Co2+ ion in crystal increased along growing direction and the effective distribution coefficient of Co2+ ion in CdWO4 crystal is less than 1. PMID- 22097826 TI - [Research on parameters optimization of laser-induced breakdown spectroscopy based experimental device]. AB - For a better application of laser-induced breakdown spectroscopy (LIBS) to coal quality analysis, it is necessary to optimize the key parameters of the experimental LIBS-based device. The relationships between the key parameters and the signal-to-noise ratios (S/N) of the elemental emission lines in the plasma spectrum of the pulverized coal were studied, according to which the optimal parameters can be selected. Experimental results indicate that the optimal settings for our LIBS-based device are laser pulse energy = 120 mJ x Pulse(-1), delay time of spectrometer = 200 ns, laser focal point be located 3-5 mm underneath the sample surface, rotation speed of sample cell = 2.7 rev x min(-1), a narrow-band filter with center frequency of 1 064 nm and a diaphragm with center hole diameter of 1.5 mm be placed in the path of the laser beam. Quantitative analysis results of pulverized coal show that, by using the optimal LIBS-based device, the standard deviation (SD) of C has been reduced from 6.7% to 1.6%, while the relative standard deviation (RSD) of other trace elements has been reduced from 28% to 10%. As a result, th accuracy has been improved greatly. PMID- 22097827 TI - [Enhancement of the radiation of laser-induced stainless steel plasmas by prefabricated keyhole]. AB - The prefabricated keyhole effects on the radiation characteristic of laser induced stainless steel plasma were investigated. A high-energy neodymium glass pulse laser was used to ablate stainless steel sample in air at atmospheric pressure. Combined-type multi-function grating spectroscope and CCD spectral acquainting and processing system were used to record plasma spectrum. The electron temperature and the full width at half maximum of spectral line, respectively. The study results showed that the spectral intensity and signal-to background ratio of laser plasma increase in the range of 71.5%-125.8% and 7.6% 18.5% respectively when a laser beam (-5 J) acted on the stainless steel sample on which prefabricated keyholes (d = 1.5 mm, h = 0.8 mm) were placed. The plasma temperature and electron density increased by about 1 200 K and 1.21 x 10(16) cm( 3), respectively. This proved that prefabricated keyhole had a significant enhancement effect on the radiation of laser-induced stainless steel plasma. PMID- 22097828 TI - [Measurement of molecular vibrational temperature of circle-dot filament in dielectric barrier discharge]. AB - Vibrational temperature in circle discharge channel and central dot discharge channel of circle-dot filament in argon/air dielectric barrier discharge was firstly measured by using optical emission spectra. The variations of the vibrational temperature in central-dot discharge channel and circle discharge channel as a function of air content were also studied. Emission spectral lines of the N2 second positive band system (C 3pi(u) -->B 3pi(g)) were used to calculate the vabrational temperature. It was found that the vibrational temperature of circle is higher than that of the central dot. The vibrational temperature of circle increases more rapidly than that of central dot although both increase with the increase in air content. These results are of great importance to the study of microdischarge in dielectric barrier discharge system. PMID- 22097829 TI - Structural characterization of lignins isolated from Caragana sinica using FT-IR and NMR spectroscopy. AB - In order to efficiently explore and use woody biomass, six lignin fractions were isolated from dewaxed Caragana sinica via successive extraction with organic solvents and alkaline solutions. The lignin structures were characterized by Fourier transform infrared spectroscopy (FT-IR) and 1D and 2D Nuclear Magnetic Resonance (NMR). FT-IR spectra revealed that the "core" of the lignin structure did not significantly change during the treatment under the conditions given. The results of 1H and 13C NMR demonstrated that the lignin fraction L2, isolated with 70% ethanol containing 1% NaOH, was mainly composed of beta-O-4 ether bonds together with G and S units and trace p-hydroxyphenyl unit. Based on the 2D HSQC NMR spectrum, the ethanol organosolv lignin fraction L1, extracted with 70% ethanol, presents a predominance of beta-O-4' aryl ether linkages (61% of total side chains), and a low abundance of condensed carbon-carbon linked structures (such as beta-beta', beta-1', and beta-5') and a lower S/G ratio. Furthermore, a small percentage (ca. 9%) of the linkage side chain was found to be acylated at the gamma-carbon. PMID- 22097830 TI - [Comparative research on the NIR and MIR micro-imaging of two similar plastic materials]. AB - The NIR/MIR micro-imaging can supply not only the information of spectra, but also the information of spacial distribution of the sample, which is superior to the traditional NIR/MIR spectroscopy analysis. In the present paper, polyethylene and parafilm, with similar appearances, were regarded as the research objects, of which the NIR/MIR micro-imaging was collected. Chemical imaging (CI) and compare correlation imaging were carried out for the two materials respectively to discuss the imaging methods of the two materials. The result indicated that the differentiation of the CI values of the two materials in the NIR/MIR CI for material II was 0.004 8 and 0.254 8 respectively, while those in the NIR/MIR CI for material I were 0.002 6 and 0.326 5, respectively. Clear CI was acquired, and the two materials could be differentiated. The result of the compare correlation imagings indicated that the compare correlation imagings, in which the NIR/MIR spectra of the two materials were regarded as reference spectra respectively, can differentiate the two materials remarkably with clear imagings. In the compare correlation imagings of MIR micro-imaging, the difference of the correlation coefficients between the two materials' MIR spectra and the reference spectrum was more than 0.12, which showed a better imaging result; while a tiny difference of the correlation coefficients between the two materials' NIR spectra and the reference spectrum could be employed to show a clear imaging result for NIR compare correlation imaging so as to differentiate the two materials. This thesis, to some extent, can supply the reference to not only the rapid discrimination of the safety of the packaging material for agri-food, but also the imaging methods for NIR/MIR micro-imaging to differentiate the different materials. PMID- 22097831 TI - [Adulteration detection of urea in milk by mid-infrared spectroscopy]. AB - In the present study, a technique of mid-infrared spectroscopy for detection of urea in milk was put forward. Eighteen adulterated milk samples with added different content of urea (1-18 g x L(-1)) were prepared. The mid-infrared spectra of these milk samples were measured. The infrared characteristics of pure milk and adulterated milk were studied, and analysis and comparisons of the differences were carried out. The absorption peak area (A1 562) of 1 562 cm(-1), which was assigned to the C-N stretching vibration for urea, and the absorption peak area (A1 464) of 1 464 cm(-1), which was assigned to the C=O stretching vibration for amide III', were calculated by origin. Linear fitting of relation was made between A1 562/A1 464 and urea concentration in milk. The results show that the A1 562/A1 464 is linear with urea concentration in milk, with a regression coefficient of 0.96. The study is important to improving quality of dairy products and protecting the benefit of consumers, and takes on crucial social significance and application prospect. PMID- 22097832 TI - [Determination of acidity and vitamin C in apples using portable NIR analyzer]. AB - Near infrared (NIR) spectroscopy technology based on a portable NIR analyzer, combined with kernel Isomap algorithm and generalized regression neural network (GRNN) has been applied to establishing quantitative models for prediction of acidity and vitamin C in six kinds of apple samples. The obtained results demonstrated that the fitting and the predictive accuracy of the models with kernel Isomap algorithm were satisfactory. The correlation between actual and predicted values of calibration samples (R(c)) obtained by the acidity model was 0.999 4, and for prediction samples (R(p)) was 0.979 9. The root mean square error of prediction set (RMSEP) was 0.055 8. For the vitamin C model, R(c) was 0.989 1, R(p) was 0.927 2, and RMSEP was 4.043 1. Results proved that the portable NIR analyzer can be a feasible tool for the determination of acidity and vitamin C in apples. PMID- 22097833 TI - [Identification of Pu'er teas with different storage years by FTIR spectroscopy]. AB - Infrared spectra of Pu'er raw tea and Pu'er ripe tea were investigated using Fourier transform spectroscopy, in order to exploit a rapid method for discrimination of aging period for Pu' er tea samples. The results showed that the two kinds of Pu'er teas shared a similar woveform of infrared spectrum. However, due to the variations of aging time, leading to different chemical composition in pu'er teas, both Pu'er raw tea and ripe tea displayed corresponding different characteristic peaks. And the extent of aging of Pu'er tea had a significant relationship with optical density and waveforms of absorption peaks in the wave number range of 1 120-1 570 cm(-1) and 400-853 cm( 1), suggesting that the extent of aging of Pu'er tea may be identified by infrared spectrum technology rapidly and simply. PMID- 22097834 TI - [Second structure of the protein factions from lotus seeds]. AB - Following the sequential Osborne extraction procedure, the proteins of lotus seeds were classified. The secondary structures of albumin, globulin, prolamine and glutelin fractions were determined by Fourier transform infrared spectroscopy (FTIR). The FTIR images of amide I and III bands from the four protein fractions were analyzed using Fourier deconvolution and curve-fitting technique. The results showed that there were minor differences in every corresponding peak position and peak area percent of secondary structure between albumin and globulin as well as between prolamin and glutelin. But there were differences in every corresponding peak position between albumin (or globulin) and prolamin (or glutelin). Especially the area percents of the corresponding nonrandom structures (alpha-helix and beta-sheet) of albumin and globulin were significantly larger than those of prolamin and glutelin. The contents of nonrandom structures of albumin and globulin extracted with 0.1 mol x L(-1) NaCl solution were about 55% and those of prolamine and glutelin fractions were only at round 40%, indicating that the secondary structures of the salt-extraction protein were ordered and stable. PMID- 22097835 TI - [Selection of visible-NIR variables based on extraction and successive projections algorithm]. AB - The pixels were 2 048 or 3 648 for the most Si charge coupled device dector. The interval between the adjacent wavelengths was few. The pretreatment could not deal with the spectra well. Spectral matrix was reconstructed by equal interval extraction in the wavelength range of 600.09-980.47nm. The variables for developing partial least squares (PLS) models were chosen by genetic algorithm (GA) and successive projections algorithm (SPA) from the pretreatment spectra. The models' predictive ability was evaluated by leave-one-out cross validation. By comparison, the best results were obtained by the SPA-PLS models. The standard errors of cross validation (SECV) were 0.661 degrees Brix, 0.067% and 2.91 mg x (100 g)(-1) for soluble solids, total adicity and vitamin C, respectively. The results suggested that the predictive ability can be improved by equal interval extraction method and SPA for determinating the quality of Nanfeng mandarin fruits. PMID- 22097836 TI - [FTIR spectroscopic analysis of Cu2+ adsorption on hematite and bayerite]. AB - The changes in surface hydroxyl structures and their absorption peaks after the adsorption of Cu2+ on the hematite and bayerite were studied by FTIR spectroscopy under the different pH values and Cu2+ concentrations. The result indicated that: (1) with the increase of Cu2+ concentrations, the H-O-H and OH deformation vibration of the hematite participated in the adsorption and Cu2+ combined with the Fe-O structure strongly, then Fe-O-(Cu) had been formed on the hematite surface. (2) In acid conditions, H+ in the solution destroyed the O-H structure of hematite surface and the existence of NO3- prompted the production of a new peak (1 131 cm(-1)). With pH value increasing, the hydroxy structure of hematite surface changed gradually from stretching vibration to deformation vibration, then the structures of Fe-OH and Fe(3+) -O(2-) constantly changed. (3) The adsorption of Cu2+ on the bayerite happened in the high wave position. With the Cu2+ concentration increasing, the free OH bending vibration, the OH- stretching vibration and its H-O-H bending vibration were all involved in the adsorption, and at the same time, Al3+ of Al-O was gradually replaced by Cu2+, which enhanced the vibration intensity of the low waves position. (4) With the increase in pH, the Al-OH bending vibration and Al-O stretching vibration changed gradually, which indicated that AlOCu+ and AlOCuOH structure had been formed on the bayerite surface after the adsorption. PMID- 22097837 TI - [Identification of yougui and jisheng shenqi pills with FTIR and EDS fingerprint spectra by new visual comparison]. AB - FTIR combined with EDS fingerprint spectra was first applied to the identification of two kind of traditional Chinese compound formulae-Yougui pill and Jisheng shenqi pills, which have the similar composition The IR FPS of extraction of two kinds of pills extracted with chloroform were measured by liquid membrane method. The exclusively characteristic peak groups of these two kinds of formulae were theoretically established based on the Shapiro-Wilk W testing method,and the characteristic radicals and compound species corresponding to each characteristic peak were determined. Meanwhile, EDS fingerprint spectra of the two kinds of original powders were also measured which can reflect the element species and content information. Based on the three kinds of information (characteristic peak groups, radicals and compound species, different elements), Yougui and Jisheng shenqi pills were identified quickly, precisely and reliably. In this method, infrared fingerprint spectra possess the similar ability with chromatograph fingerprint spectra in identification of traditional Chinese compound formulae. The results show that the new visual comparison method is suitable for identifying traditional Chinese compound formulae with the same dosage-form and similar composition. PMID- 22097838 TI - [Research on the measurement of urinary albumin by visible-near infrared spectroscopy]. AB - The urinary albumin (UMALB) is the most reliable diagnostic indicator of renal injury in clinical. Attempting to realize the rapid and free reagent measurement of UMALB, the visible-near infrared multiple optical path length spectra of 207 urine samples were collected. By the nonlinear characteristics of multiple optical path length spectra, more information about the component of sample contents can be obtained. The PLS model of the spectra and UMALB was firstly established. Based on it, the PLS-ANN modeling method was built to introduce nonlinear information. By contrast, the PLS-ANN modeling method can obtain a better model to improve the accuracy of quantitative analysis. The R2 of predicted model was 0.951 1 and the RMSEP was 5.02 mg x L(-1). The results showed the feasibility of the visible-near infrared multiple optical path length spectroscopy technique for urinary albumin analysis. This research establishes the foundation of detecting the urinary albumin and other components free of reagent conveniently and rapidly. PMID- 22097839 TI - [Study on the application of DBPSO algorithm to thickness measurement of surface insulation coating of silicon steel by NIR spectrometry]. AB - A novel thickness measurement NIR spectrometry for surface insulation coating of silicon steel based on discrete binary particle swarm optimization (DBPSO) algorithm is presented. First, we used NIR spectrometer to collect the NIR spectra of insulation coating of silicon steel, and then, DBPSO algorithm was used to select the optimal wavelength variates and composed a new spectra set. Last, the authors created the thickness quantitative analysis model using kernel partial least square algorithm. The experimental results show that the absolute error range analyzed by created model was from -0.12 to 0.19 microm, and the maximal relative error was 14.31%, which completely met the practical measurement need. The research indicates that DBPSO is effective wavelength selection methods, which can efficiently select the wavelength variates carrying more useful information, improve the analysis accuracy and speed. And the NIR spectroscopy is an effective measurement method for thickness analysis of silicon steel insulation coating. PMID- 22097840 TI - [Analysis and evaluation of different radial parts of Cordyceps kyushuensis by Fourier transform infrared spectroscopy]. AB - Fourier-transform infrared spectroscopy (FTIR) and second derivative spectra were used to analyze and evaluate the different parts of Cordyceps kyushuensis Kob in the present work. The results showed that C. kyushuensis contained proteins, polysaccharides, nucleosides, lipids and other active ingredients, the single dimensional IR spectra of the various parts were highly similar, the similarity coefficient between the cultured stroma and medium reached up to 0.992 7, and the natural stroma was more different from the parasites, with similarity coefficient of 0.949 9. Second derivative spectrum further enriched and confirmed the feature of corresponding spectrum peaks, proved the existence of active substances such as cordycepin and adenosine, and prompted the presence of alpha- and beta glycosidic bonds. The diversity and complexity of chemical constituents in different parts of C. kyushuensis were synthetically described by IR spectra, which provided a fast, comprehensive and objective approach to the analysis and evaluation of the imperceptible differences, and the quality control of Cordyceps. This work supplies a theoretical basis for development and utilization of genetic resources C. kyushuensis. PMID- 22097841 TI - [A new approach to rapid determination of compound fertilizer composition]. AB - In the present paper, a new approach to rapid determination of compound fertilizer composition was introduced, namely first preparing aqueous solution of solid fertilizer, then predicting the compound fertilizer composition using the near infrared transmission spectra of the solution. Using the new method, models were built by means of PLS regression, and the standard errors of prediction of total nitrogen content, P2O5 content, and K2O content are 0.5, 0.7, 0.8, and 2.0, respectively. This has solved the problem of large prediction error for K content of compound fertilizer using near infrared reflectance spectroscopy due to the fact that KCl dose not have near infrared absorption, and achieved rapid analysis of all compositions of compound fertilizer in 5 minutes. PMID- 22097842 TI - [Water Raman spectrum suppression with low-pass filter in underwater in-situ Raman spectroscopy]. AB - As a powerful tool for studying chemical structures, Raman spectroscopy has been used in aquatic environments in-situ measurement widely, and has been used in deep sea research recently. For underwater in-situ detection, O-H vibration Raman peak of water is inherent and strong compared with other dissolved matter's Raman signals. When the authors want to get a good SNR Raman signal of dissolved matter by increasing detection time, O-H vibration Raman peak of water will get to saturation easily, which influences other Raman signal's detection. In the present paper, a specially designed short-pass optical filter was used for suppression of water's O-H vibration Raman peak. The authors calculated the suppression effect of short-pass optical filter with linear and exponential edges. The simulation shows that exponential edge filter has better performance and can suppress water's O-H vibration Raman peak effectively. The experiment also proves the calculation results. With the suppression optical filter, the intensity of water's O-H vibration Raman signal and other dissolved matters' become similar. And the influence of suppression optical filter on other dissolved matters' Raman signal is little. So the suppression optical filter is feasible for in-situ underwater Raman spectroscopy. PMID- 22097843 TI - [Mid-infrared and Raman spectral analysis of geometrically frustrated natural atacamite]. AB - At room temperature, the mid-infrared spectra of geometrically frustrated natural atacamite (hydroxyl copper chloride, beta-Cu2(OH)3Cl) in the range of 4 000-400 cm(-1) were measured by FTIR spectrometers, and meanwhile its Raman spectrum in the range of 4 000-95 cm(-1) was obtained by Jobin Yvon LabRAM HR800 Raman spectrometer. According to its crystal structure parameters, the authors confirmed the characteristic peaks of sample 4 000-2 500-1 000 cm(-1) in the functional group region and 1 000-550-200-95 cm(-1) in the fingerprint region, and also explored its microscopic origin Five distinct regions were assigned: the hydroxyl stretching vibration v(O-H) determined by the overall environment around the hydroxyl group; the overtones generated by the sum or multiplication of fundamental frequencies of hydroxyl bending vibration; the hydroxyl bending vibration modes delta(O-H) of the combination of delta(Cu-O-H) and delta(O H...HCl); the vibration modes of strongly bonded planar CuO4 units; the vibration modes of weakly bonded linear-triatomic chain Cl-Cu-O/Cl. The bands were assigned in accordance with its crystal structure parameters, which is more reasonable to establish the relationship between its molecular structure and its respective spectral properties. PMID- 22097844 TI - [3-D fluorescence properties of petrochemical wastewater]. AB - Petrochemical wastewater is one of major types of industrial wastewater in China. It is of huge quantity and causes serious pollution. Wastewater contains lots of fluorescence matters. Its fluorescence spectrum could exhibit organic components and unique for each sample like fingerprint. Thus it is referred to as fluorescence fingerprint of water quality, in brief aqueous fingerprint. This paper presented that there were almost 10 peaks in the aqueous fingerprint of petrochemical wastewater from a large-scale petrochemical plant, including the peak at the excitation/emission wavelengths (lambda(ex)/lambda(em)) of around 230/340 nm. That peak exists in the fluorescence spectra of various petroleum materials. The aqueous fingerprint was divided into 3 zones according to the relationship of fluorescence intensity of peaks: the linear relation between the peaks from different zones was not significant while that between the peaks from same zone was significant with coefficients of above 0.85. The zone around lambda(ex)/lambda(em) = 230/305 nm might relate to benzene compounds and the zone around lambda(ex)/lambda(em) = 220-320/230-440 nm (excluding the zone around lambda(ex)/lambda(em) = 230/305 nm) showed close relation with the raw materials (petroleum materials). The intensity of each peak had a fixed range. That range and relationships between peaks could be the evidences for diagnosing if the performance of the production processes is proper. PMID- 22097845 TI - [Study on the transient and steady state property of fluorescence of free radical photoinitiator]. AB - The fluorescence characteristic of various free radical photoinitiators was investigated by fluorescence spectroscopy. The influence of conjugated structure on fluorescence spectrum was analyzed from the molecular structure. The results show that: the wave length of fluorescence excitation spectrum gradually augments with the conjugative effect enhancement, and so does the peak of fluorescence emission spectrum. The transient fluorescence spectrum of photoinitiator is affected by electron groups and the fluorescence decay of photoinitiators with electron-withdrawing groups is faster than that of photoinitiators with electron donating groups. The excitation peak of photoinitiator has evident red shift with the polarity of solvent increasing, which shows that transition type is pi-pi* transition, and the fluorescence decay is postponed with the solvent glutinosity changing. When the photoinitiator density is at 10(-2) mol x L(-1), the fluorescence decay is evidently fast because of quenching effect caused by self absorption and collisions between particles. PMID- 22097846 TI - [Studies on the interaction of rhein with bovine serum albumin by spectroscopic and voltammetric methods]. AB - The interaction between rhein and bovine serum albumin(BSA) was studied by UV Visible, fluorescence spectroscopy and circular dichroism in conjunction with electrochemical method. The results indicated that rhein has a powerful ability to quench the albumin's fluorescence in a static mode. The binding constants(KA) and binding site numbers (n) obtained at different temperatures were 3.67 x 10(5), 0.99 (298 K) and 2.60 x 10(4), 0.83 (309 K) respectively. According to the thermodynamic parameters the main sorts of binding force of rhein-BSA was fixed as electrostatic. The distance between donor and acceptor in rhein-BSA was 3.28 nm based on the Forster energy transfer theory. Results of the circular dichroism and synchronous fluorescence show that the binding can cause conformation change of BSA. PMID- 22097847 TI - [Using extraction of red edge position to validate consistency of hyperspectral imaging and non-imaging data]. AB - Using Pushbroom imaging spectrometer (PIS) and FieldSpec ProFR2500 (ASD), spectral reflectances of winter wheat and maize at different stages were collected synchronously. In order to validate the reliability of imaging spectral data, the red edge position of hyperspectral data for PIS and ASD were extracted by different algorithms, respectively. The following results were obtained: (1) The original spectrum of both instruments had high inosculation in red light region (670-740 nm); (2) With the spectra collected under laboratory condition (maize leaf), the extracted red edge position was is concentrated between 700 and 720 nm for the two instruments; (3) With the spectra collected undre field condition (wheat leaf), the extracted red edge position for PIS and ASD were different, the red edge position of PIS data was in 760 nm, while it was in 720 nm for ASD data. The main reason might be that the imaging spectral data were influenced by oxygen absorbtion; (4) the red edge rangeability of PIS and ASD were different, but the trends were the same. The above results could provide some references for hyperspectral imaging data's extensive application. PMID- 22097848 TI - [A method of endmember extraction in hyperspectral remote sensing images based on discrete particle swarm optimization (D-PSO)]. AB - For the inaccuracy of endmember extraction caused by abnormal noises of data during the mixed pixel decomposition process, particle swarm optimization (PSO), a swarm intelligence algorithm was introduced and improved in the present paper. By re-defining the position and velocity representation and data updating strategies, the algorithm of discrete particle swarm optimization (D-PSO) was proposed, which made it possible to search resolutions in discrete space and ultimately resolve combinatorial optimization problems. In addition, by defining objective functions and feasible solution spaces, endmember extraction was converted to combinatorial optimization problem, which can be resolved by D-PSO. After giving the detailed flow of applying D-PSO to endmember extraction and experiments based on simulative data and real data, it has been verified the algorithm's flexibility to handle data with abnormal noise and the reliability of endmember extraction were verified. Furthermore, the influence of different parameters on the algorithm's performances was analyzed thoroughly. PMID- 22097849 TI - [Hyperspectral feature band selection based on mean confidence interval and tree species discrimination]. AB - In the present study, based on the leaf-level hyperspectral data of BaiMu, LeiZhu and WuHuanZi, the authors come up with two solutions through the theory of statistics; the first one is that optimal discriminating band between tree species is extracted by mean interval confidence, the other one is that tree species is discriminated by the Manhattan distance and the Min Max interval similarity. The research results showed that (1) the optimal discriminating bands between BaiMu and LeiZhu are around 350-446, 497-527, 553-1 330, 1 355-2 400 and 2 436-2 500 nm; the optimal discriminating bands between BaiMu and WuHuanZi are around 434-555, 580-1 903, 1 914-2 089, 2 172-2 457 and 2 475-2 500 nm; the optimal discriminating bands between LeiZhu and WuHuanZi are around 434-555, 580 1 903, 1 914-2 089, 2 172-2 457 and 2 475-2 500 nm; and this result is helpful for us to find maximum difference to identifying tree species respectively. (2) In these optimal discriminating bands, we find that the Manhattan distance between the same species is far less than the different species; but the Min-Max interval similarity between the same species is far more than the different species, so this result could help us to discriminate and identify different types of tree species effectively. PMID- 22097850 TI - [A remote sensing band simulation approach based on image spectral library]. AB - The authors proposed an image spectral library based band simulation method. Firstly, the authors clustered the reference image which has the same class composition with the target image by using its pixel spectrum similarity. Secondly, the authors fetched sample from the reference image base on the former cluster image, and then built the image spectral library. Thirdly, the authors fetched the same count of each type of samples to train the simulation model. Finally, the authors simulated the target band of the target image. The experiment results show that: firstly, this method can be more precise to simulate TM blue band, and increase more than 1.2 RMSE value than that of the "Spectral Library-image" model and more than 0.6 RMSE value than that of the "image-image" model. On the other hand, our method is more stable and reliable than the "image-image" and "Spectral Library-Image" simulation model; finally, this method can be successfully applied to the blue band simulation that SPOT and MSS lacked. PMID- 22097851 TI - [The hierarchical clustering analysis of hyperspectral image based on probabilistic latent semantic analysis]. AB - The paper introduces the Probabilistic Latent Semantic Analysis (PLSA) to the image clustering and an effective image clustering algorithm using the semantic information from PLSA is proposed which is used for hyperspectral images. Firstly, the ISODATA algorithm is used to obtain the initial clustering result of hyperspectral image and the clusters of the initial clustering result are considered as the visual words of the PLSA. Secondly, the object-oriented image segmentation algorithm is used to partition the hyperspectral image and segments with relatively pure pixels are regarded as documents in PLSA. Thirdly, a variety of identification methods which can estimate the best number of cluster centers is combined to get the number of latent semantic topics. Then the conditional distributions of visual words in topics and the mixtures of topics in different documents are estimated by using PLSA. Finally, the conditional probabilistic of latent semantic topics are distinguished using statistical pattern recognition method, the topic type for each visual in each document will be given and the clustering result of hyperspectral image are then achieved. Experimental results show the clusters of the proposed algorithm are better than K-MEANS and ISODATA in terms of object-oriented property and the clustering result is closer to the distribution of real spatial distribution of surface. PMID- 22097852 TI - [Synthesis and spectral characteristic of pharmaceutical dipfluzine hydrochloride benzoic acid co-crystal]. AB - Pharmaceutical co-crystals can improve the chemical and physical properties of active pharmaceutical ingredient (API), which is new idea and expected to provide new stable structures. Pharmaceutical co-crystals have the potential to be much more useful in pharmaceutical products than salts, solvates or hydrates, polymorphs and stoichiometric solvates (pseudo-polymorphs). In our study, dipfluzine hydrochloride-benzoic acid co-crystal was synthesized by solid co grinding. The samples were subjected to IR, DSC, XRD, Raman and THz spectral analysis. The results indicated that dipfluzine hydrochloride-benzoic acid complex was new phase compared with the single API and CCF. THz-TDS characterization indicated that hydrogen bond formed between API and CCF, which confirmed the formation of co-crystal. PMID- 22097853 TI - [Quantitative spectrum analysis of characteristic gases of spontaneous combustion coal]. AB - Aimed at the characteristics of spontaneous combustion gas such as a variety of gases, lou limit of detection, and critical requirement of safety, Fourier transform infrared (FTIR) spectral analysis is presented to analyze characteristic gases of spontaneous combustion In this paper, analysis method is introduced at first by combing characteristics of absorption spectra of analyte and analysis requirement. Parameter setting method, sample preparation, feature variable abstract and analysis model building are taken into consideration. The methods of sample preparation, feature abstraction and analysis model are introduced in detail. And then, eleven kinds of gases were tested with Tensor 27 spectrometer. CH4, C2H6, C3H8, iC4H10, nC4H10, C2 H4, C3 H6, C3 H2, SF6, CO and CO2 were included. The optical path length was 10 cm while the spectra resolution was set as 1 cm(-1). The testing results show that the detection limit of all analytes is less than 2 x 10(-6). All the detection limits fit the measurement requirement of spontaneous combustion gas, which means that FTIR may be an ideal instrument and the analysis method used in this paper is competent for spontaneous combustion gas measurement on line. PMID- 22097854 TI - [Use of ensemble Kalman smoother algorithm for the time-series retrieval of leaf area index from remote sensing data]. AB - In the present paper, the empirical LAI dynamic model was constructed using the MOD15A2 data set, and the canopy radiative transfer model MCRM2 was coupled with the LAI dynamic model through LAI. The scheme was proposed to retrieve LAI by assimilating MOD09A1 data set into the coupled model. The ensemble Kalman smoother (EnKS) method was first introduced. In order to preferably assess the feasibility of EnKS, the LAI retrieval results of EnKS were compared with the ensemble Kalman filter (EnKF) solutions and MODIS LAI product. The results indicated that the EnKS method achieved ideal results. The retrieved LAI temporal profiles by the EnKS method were smoother and more continuous than the EnKF solutions and the MODIS LAI product, which were in good agreement with the realistic LAI climatology. The developed inversion method in this paper can be applied to retrieve LAI time--continuous profiles effectively. PMID- 22097855 TI - [Effect of carbon nanotubes on the crystallization behaviors of MC nylon 6]. AB - Multi-walled carbon nanotubes bearing hydroxyl group were modified with toluene diisocyanate (TDI) and stabilized with caprolactam. The functionalized carbon nanotubes were used to prepare monomer casting polyamide 6(MC nylon 6)/carbon nanotubes nanocomposites. The results of FTIR proved that isocynate groups have been incorporated into carbon nanotubes successfully. XRD results showed that the addition of the functionalized carbon nanotubes has no significant influence on the crystal structure of MC nylon 6, whereas the untreated carbon nanotubes could hinder the growth of alpha2-crystal of nylon 6; with the loading of 0.3 Wt% of the functionalized carbon nanotubes, the crystallinity degree of the nanocomposites is almost equal to that of pure MC nylon 6, whereas as the loading increased to 0.5 Wt%, the crystallinity degree of MC nylon 6 decreased. DSC revealed that carbon nanotubes in MC nylon 6 acted as effective nucleation agents. The peak temperature of crystallization for MC nylon 6 increased by 10 degrees C from 173.4 to 183.5 degrees C, and the temperature range of crystallization decreased, indicating that the carbon nanotubes act as heterogeneous nucleation agents for MC nylon 6. PMID- 22097856 TI - Coniferous canopy BRF simulation based on 3-D realistic scene. AB - It is difficulties for the computer simulation method to study radiation regime at large-scale. Simplified coniferous model was investigated in the present study. It makes the computer simulation methods such as L-systems and radiosity graphics combined method (RGM) more powerful in remote sensing of heterogeneous coniferous forests over a large-scale region. L-systems is applied to render 3-D coniferous forest scenarios, and RGM model was used to calculate BRF (bidirectional reflectance factor) in visible and near-infrared regions. Results in this study show that in most cases both agreed well. Meanwhile at a tree and forest level, the results are also good. PMID- 22097857 TI - Spectral reflectance characteristics of different snow and snow-covered land surface objects and mixed spectrum fitting. AB - The field spectroradiometer was used to measure spectra of different snow and snow-covered land surface objects in Beijing area. The result showed that for a pure snow spectrum, the snow reflectance peaks appeared from visible to 800 nm band locations; there was an obvious absorption valley of snow spectrum near 1 030 nm wavelength. Compared with fresh snow, the reflection peaks of the old snow and melting snow showed different degrees of decline in the ranges of 300-1 300, 1 700-1 800 and 2 200-2 300 nm, the lowest was from the compacted snow and frozen ice. For the vegetation and snow mixed spectral characteristics, it was indicated that the spectral reflectance increased for the snow-covered land types (including pine leaf with snow and pine leaf on snow background), due to the influence of snow background in the range of 350-1 300 nm. However, the spectrum reflectance of mixed pixel remained a vegetation spectral characteristic. In the end, based on the spectrum analysis of snow, vegetation, and mixed snow/vegetation pixels, the mixed spectral fitting equations were established, and the results showed that there was good correlation between spectral curves by simulation fitting and observed ones (correlation coefficient R2 = 0.950 9). PMID- 22097858 TI - [Study of ignition characteristic of DC voltage plasma ignitor]. AB - The changing law between interelectrode current, discharge characteristic and jet characteristic of plasma ignitor under different inlet Ar pressure and working current was researched by adopting self-made plasma ignitor. Still, four channels CCD spectrometer was adopted to measure the spectrum characteristic at the exit of ignitor and electron temperature of plasma was calculated according to the spectrum characteristic. The results show that the interelectrode current gradually reduced with rising inlet Ar pressure; The jet length of plasma ignitor firstly increased then reduced with rising inlet Ar flowrate, and also increased with rising working current; The working current of plasma ignitor reduced with rising inlet Ar flowrate, and increased with rising source output current; the electron temperature of plasma ignitor jet increased with rising working current and reduced with rising Ar flowrate. The research results are of certain guidance meanings and reference values for the practical application of plasma ignition system in aeroengine. PMID- 22097859 TI - [Light absorption characteristic of natural pyrite]. AB - In the present paper, the natural pyrite was the sample. With the UV-visible near infrared spectrophotometer Cary 500, we measured the absorption and reflection spectra of the sample within 200-2 000 nm range, calculated the absorption coefficient and figured out the forbidden band of the sample according to the Tauc regulation. The authors discovered that the light absorption coefficient of natural pyrite measured is 10(5) order of magnitude; in the absorption pattern we found obvious shoulder line structure and we can judge that the sample belongs to indirect forbidden band semiconductor, its forbidden band was 0.64 eV in width and the "limit conversion efficiency" corresponding to 0.64 eV could reach 14% or so. With the comparison of the results of this paper and the forbidden band of the solar battery materials at present in common, this paper mainly analyzed the effect of the light absorption coefficient and forbidden band on the photoelectric conversion efficiency of pyrite. The authors found that its high absorption coefficient provided the possibility that pyrite will be used as solar battery with the film form, but its forbidden band was narrower than the theoretical number. The authors could broaden its forbidden band or make composite films to use. PMID- 22097860 TI - [Comparison between myoglobin and its mutant(D60K) interacting with hydrogen peroxide by spectrum]. AB - To characterize the roles played by surface-charged residue Asp60 in the structure stability of myoglobin when it was replaced with Lys, the interaction of myoglobin[Mb(WT)] and its mutant[Mb(D60K)] with hydrogen peroxide (H2O2) were studied by the method of ultraviolet-visible (UV-Vis) absorption spectroscopy, fluorescence spectroscopy and stopped-flow fluorescence spectroscopy under simulative physiological conditions. There are remarkable differences between Mb(D60K) and Mb (WT) in the UV-Vis absorption spectroscopy and fluorescence spectroscopy of iron porphyrin during the process of interaction. Although we only altered one external amino acide, the data showed that the function and structure stability of Mb(D60K) was greatly changed. Furthermore, results from synchronous fluorescence spectroscopy and stopped-flow fluorescence spectroscopy all indicated that H2O2 had less effect on the structure of Mb(D60K) while the structure of Mb(WT) was notably changed. From a comprehensive and comparative data analysis, the authors determined that the structure of Mb(D60K) was improved when it interacted with H2O2. PMID- 22097861 TI - [Determination of serum proteins by resonance light scattering method with lidocaine as a probe]. AB - A new method for the determination of bovine serum albumin (BSA) and human serum albumin (HSA) was developed by using resonance light scattering (RLS) technique via an interaction of serum albumin with lidocaine and sodium dodecylbenzene sulphonate (SDBS). The RLS intensity of serum albumin was enhanced in the presence of lidocaine and SDBS. The influences of some experimental factors, including incubation time, addition sequence of reagents, pH values, foreign substances and the concentrations of lidocaine and SDBS, on the enhancement of the RLS intensity were investigated. Under the optimal conditions, the enhanced RLS intensities were proportional to the concentrations of serum albumin in the range of 1.0-45.0 mg x L(-1) for BSA and 0.5-30.0 mg x L(-1) for HSA. The method was successfully applied to the determination of real human serum samples, with the relative standard deviations of 4.9%-5.7% (n = 5) and standard addition recoveries of 90%-103%. The method only involves the use of conventional fluorescence spectrometer and chemical reagents. It is simple, easy to operate and sensitive with the limit of detection of 0.14 mg x L(-1). The fresh human serum samples can be directly analyzed without the need of any prior pretreatment. The method can be a good alternative of choice for the determination of BSA and HSA. PMID- 22097862 TI - [Spectroscopic study on the combustion reaction characteristics of methylcyclohexane]. AB - Using a measurement system consisting of monochromators, photomultiplier tubes, piezoelectric pressure sensors and a digital oscilloscope, characteristic emissions of intermediate products OH, CH and C2 produced in the combustion reaction of methylcyclohexane were measured behind reflected shock waves in a shock tube, and ignition delay times of methylcyclohexane/ oxygen/argon were acquired. Experimental conditions cover temperatures from 1 164 to 1 566 K, pressures from 1.03 to 1.99 atm, a fuel concentration of 1.0%, and an equivalence ratio of 1.0. Combustion reaction characteristics of methylcyclohexane were obtained qualitatively by analyzing emissions from intermediate products OH, CH and C2. The measured ignition delay times agree with available experimental data and the prediction of a combustion reaction mechanism. Current work provides experimental data for constructing and validating the combustion reaction mechanism of methylcyclohexane. PMID- 22097863 TI - [Research on spectral characteristics of Yb3+ doped double-cladding large-mode area micro-structured optical fiber]. AB - Yb3+ doped double-cladding large-mode-area micro-structured optical fibers (Micro structured fibers, MSF) are the ideal medium for the super high-power optical fiber laser applications. In the present paper, the authors fabricated the Yb3+ doped silica-based glass using the method of non-chemical vapor deposition, and fabricated the Yb3+ doped double-cladding large-mode-area MSF by stack-drawing method using this glass as the core of MSF, according to the design requirements. Fluorescence spectrum of the MSF was obtained using Ti: sapphire femtosecond laser with the wavelength of 975 nm and LD laser with the wavelength of 980 nm as pumping source. The experimental results show that the optical fiber has strong fluorescence at the wavelength of 1 050 nm, and it can inhibit generation of cooperative luminescence effectively. PMID- 22097864 TI - [Preparation and catalytic activity of surface-modification CNTs/TiO2 composite photocatalysts]. AB - A novel kind of carbon nanotubes/titanium dioxide (CNTs/TiO2) composite photocatalyst was prepared by a modified sol-gel method in which the nanoscaled TiO2 particles were uniformly deposited on the CNTs modified with poly(vinyl pyrrolidone) (PVP). The composites were characterized by a range of analytical techniques including high resolution transmission electron microscopy (TEM), X ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The results show the successful covering of the CNTs with PVP, forming core-shell structure. The nanoscaled TiO2 particles were uniformly deposited on the surface of CNTs reducing the bare CNTs which avoid losing the absorption and scattering of photons. The combination of CNTs and TiO2 particles imply the enhanced interactions between the CNTs and TiO2 interface which possibly becomes heterojunction. The composites become mesoporous crystalline TiO2 (anatase) clusters after annealing at 500 degrees C, and the surface area increases obviously. The photocatalytic activities of surface modification CNTs/TiO2 (smCNTs/TiO2) composites are extremely enhanced from the results of the photodegradation of methylene blue (MB). PMID- 22097865 TI - [Study on the distribution of plasma parameters in electrodeless lamp using emission spectrometry]. AB - Electrodeless lamp in pear shape was ignited using inductively coupled discharge setup and Ar-Hg mixtures as working gas. The changes in electronic temperature and density with axial and radial positions at 5 s of igniting were studied by means of emission spectrometry. The changes in electronic temperature were obtained according to the Ar line intensity ratio of 425.9 nm/ 750.4 nm. And the variations in electronic density were analyzed using 750.4 nm line intensity. It was found that plasma electronic temperature and density is various at different axial or radial positions. The electronic temperatures first increase, then decrease, and then increase quickly, and finally decline. While the electronic density firstly increase quickly, the decrease, and then rise slowly and finally decline again with axial distance increasing. With radial distance increasing, electronic temperature increases to a stable area, then continues to rise, while electronic density decreases. PMID- 22097866 TI - [A real-time determination method with laser measurement for depth profile analysis of GD-OES]. AB - This paper presents the traditional methods of GD depth analysis method and also its limitations, and the earlier studies of real-time depth measurement technology. A new method of real-time depth determination by laser technology for GD-OES depth analysis is proposed. The real-time depth measurement system is composed of laser displacement sensor and new designed Grimm-type GD source based on laser measurement method, and the system design and technical principles are described in detail. Sputtering depth measurement signal and element spectrum signal can be synchronously collected by this system. The displacement phenomenon of glow discharge source during real-time sputtering depth measurement process is analyzed. The real-time sputtering depth measurement curve of zinc alloy standard sample was tested by two laser displacement sensors measurement system. The actual value of sputtering depth was obtained by adding the depth measurement curve of sputtering surface and the reference plane curve, and the actual depth result is in line with Dektak8-type surface profilometer. PMID- 22097867 TI - [Plasma spectral analysis of laser cleaning process in air]. AB - It is quick and accurate to on-line monitor the sample condition of laser cleaning by means of laser-induced plasma spectrum in air. In the present article, the echelle grating spectrometer was used to detect the plasma spectral lines induced by pulsed laser interaction with copper coin samples with or without contamination. The spectrogram showed that there were clear Cu I spectrum lines and air atom spectrum lines of N I and O I. In order to eliminate the uncertainty of single measurement, the statistical regularity of N I and O I spectrum lines was analyzed. Their intensity distribution laws were consistent and their relative standard deviations were the same basically. So a single measurement spectrum could be used to monitor cleaning process. The spectra of copper samples with contamination consisted of many elements atomic spectral lines and continuous spectral lines. But there are Cu I spectral lines in the spectra of clean copper samples. As a result, the authors could detect the change of spectral lines to judge whether the laser cleaning samples were clean. PMID- 22097868 TI - [Quantitative analysis of Mn, Cr in steel based on laser-induced breakdown spectroscopy]. AB - Quantitative analysis of trace elements such as manganese and chromium in steel was performed employing laser-induced breakdown spectroscopy (LIBS) technique in the present paper. The experimental measurements indicate that the optimal delay, focal plane and detecting position from the sample surface are 2 micros, -3.5 mm and 1.5 mm,respectively. Mn I: 403.07 nm and Cr I : 427.48 nm were selected as the analytical lines and their contents in the target steel sample were analyzed with traditional quantitative analysis and internal standard methods. Comparison of the results with two kinds of quantitatively analytical methods show that the coefficients of determination gained by internal standard method are 0.998 and 0.979 which are much better than the results obtained by traditional quantitative analysis method. According to the established calibration curve by internal standard method the detection limits of manganese and chromium calculated are 0.005% and 0.040 6%, respectively. PMID- 22097869 TI - [Study on of deferrization mechanism of apoferritin and the effect of spectra variation with holoferritin]. AB - The deferrization mechanism of apoferritin was established, and the spectra variation of apoferritin was compared with that of holoferritin. Sodium hyposulfite is a strong reducing agent, therefore, was applied to deoxidize holoferritin to release iron ion, and connection of iron of buffer was measured by the 2,2-dipyridyl. Apoferritin was detected by ICP-MS. Holoferritin was found to have no absorption compared with apoferritin by UV analysis, and have no fluorescence emission spectra in contrast with apoferritin by fluorescence analysis. PMID- 22097870 TI - Content of nutritional elements in sudangrass and ryegrass determined by ICP-AES. AB - The sudangrass (Sorghum sudanense) and ryegrass (Lolium multi florum L.) rotation is a new type of cropping system, which has developed rapidly in recent years in the south of China. The contents of nutritional elements for forage grass in the sudangrass and ryegrass rotation system were determined by ICP-AES. The results showed that there were abundant and essential nutritional elements for animals in sudangrass and ryegrass. The contents of P, K, Ca, Mg, S, Fe, B, Cu, Zn and Mn for sudangrass were 0.20% -0.29%, 1.94%-2.57%, 0.62%-0.97%, 0.39%-0.69%, 0.12% 0.18%, 108.35-180.12, 3.04-5.96, 6.17-10.02, 20.37-31.36 and 46.80-101.29 mg x kg(-1), respectively. The contents of P, K, Ca, Mg, S, Fe, B, Cu, Zn, Mn for ryegrass were 0.39%-0.70%, 3.77%-5.07%, 0.61%-0.84%, 0.28% -0.47%, 0.32%-0.41%, 291.65- 632.20, 2.13-3.23, 13.29-15.19, 30.73-42.98 and 92.08-156.04 mg x kg(-1), respectively, and there were differences between various periods in nutritional elements in the two forage grasses. The application of ICP-AES could reflect fast and efficiently the content of nutritional elements for forage grass as animals feed. PMID- 22097871 TI - [Determination of Cr, Ni, Cu, Mn, P, Si, Mo and Ti in high chromium cast iron by inductively coupled plasma atomic emission spectrometry]. AB - The high-chromium cast iron sample was microwave-assisted digested with aqueous regia in a closed vessel. Series standards were prepared with matching Fe matrix and adding Y as internal standard. Line intensities of the prepared standards and the digested sample solutions were determined by inductively coupled plasma atomic emission spectrometry. Accuracy of the proposed method was verified by the analysis of three national standard Materials GSBH 41018, GBW 01120 and GBW 01121, and the results were well agreed with the certification data. PMID- 22097872 TI - [Study of symbolic element in roasting slag of pyrite by inductively coupled plasma mass spectrometry]. AB - In the present paper, the correlations between sixteen elements from the dry method roasted dust-slag of pyrite and sixteen elements from the soil layer near and far from the store area were studied by ICP-MS. Similar radio and outstanding different radio of the elements between the dust-slag and the soil were studied too. It was discovered that in the pollution soil layer Tl, Cd, Cs, Cu, Zn, Mn, Pb and Ni were easy to be identified and had similar radio with the elements in the dust-slag. But only Tl, Cd, Zn and Ni are suitable for criterion of element similar properties. In dust-slag and soil, distinct composition element radios of Tl, Cs, Co, Mo, Zn, Cr, V, Sr, Sb, Pb, Rb, Mn and Ni had striking differentiation. Only Tl, V, Sb and Cu corresponded to both the uncorrelated elements analysis of surface layer and middle-base layer soil. Tl could be used as an inspection target of similar elements and outstanding different elements between the dust-slag and the soil in the meanwhile. So we suggested that Tl can be used as a symbolic element in the roasting dust-slag of pyrite to find the dust-slag of pyrite in dust-recognition and to differentiate the metallurgy dust of pyrite and soil dust. PMID- 22097873 TI - [Determination of metals in waste bag filter of steel works by microwave digestion-flame atomic absorption spectrometry]. AB - A method of microwave digestion technique-flame atomic absorption spectrometry was proposed to determine the total contents of Cu, Zn, Pb, Cd, Cr and Ni in five different kinds of waste bag filters from a steel plant. The digestion effects of the six acid systems on the heavy metals digestion were studied for the first time. The relative standard deviation (RSD) of the method was between 1.02% and 9.35%, and the recovery rates obtained by standard addition method ranged from 87.7% to 105.6%. The results indicated that the proposed method exhibited the advantages of simplicity, speediness, accuracy and repeatability, and it was suitable for determining the metal elements of the waste bag filter. The results also showed that different digestion systems should be used according to different waste bag filters. The waste bag filter samples from different production processes had different metal elements content. The Pb and Zn were the highest in the waste bag filters, while the Cu, Ni, Cd and Cr were relatively lower. These determination results provided the scientific data for further treatment and disposal of the waste bag filter. PMID- 22097874 TI - [XPS and SEM spectroscopy study of hyperdispersant on atrazine surface]. AB - The authors studied the electronic condition of comb-shaped copolymer of polycarboxylic acid type hyperdispersant adsorbed on the surface of atrazine particles with X-ray photoelectron spectroscopy (XPS). The thickness of the adsorption was calculated. The results suggested that after adsorbing the dispersant, the peak intensity of N(1s) and Cl(2p) of the interface of atrazine particle decreased sharply, while the absorption of Cl(2s) almost diminished. Meanwhile the peak intensity of C(1s), O (1s) and Na(1s) increased obviously owing to the second emission of C, O, and Na from the dispersant molecule. After adsorption, the dispersant formed a favorable protecting membrane on the surface of atrazine particles whose thickness was about 24 nm. The authors also studied the surface state of the sample with scanning electron microscope (SEM). The results of which showed that after adsorption, the atrazine particles became smaller and their dispersion was in good order. These changes allowed the atrazine particle to have a stable suspension property. This study provided significant information for the application of environment friendly atrazine suspension concentrate. PMID- 22097875 TI - [The influence of the gain on ignition and correction in X-ray fluorescence spectrometry]. AB - Research on the gain on ignition question for preparing ore with fusion sample preparation technique was done, and a new correction method was worked out. After fusion sample preparation, sulphide ore would have a lot of sulfate, which would change the sample matrix dramatically, and the matrix effect was corrected with errors. In this paper, a new solution to measuring gain on ignition was put forward, and it was committed step that the sample having gain on ignition was redefined by sample having loss on ignition. Through conversion, the gain on ignition was corrected by subtraction method, and the matrix effect was corrected by theoretical influence coefficients. The analysis results of redefinition samples were converted into the primal samples lastly. The project took copper concentrates as the experimental object, it was found that the gain on ignition of this method was obviously different from the gravimetric method, but through influence evaluation, this error had little effect on test results, and may be reduced by flux. After correction of the gain on ignition, the standard deviation of the elements calibration curves for Cu, Fe and S were less than 0.14%, 0.074% and 0.14% respectively, which were obviousely superior to 0.21%, 0.15% and 0.19%. The results got from this method were in satisfactory agreement with certified values. PMID- 22097876 TI - [Searching QSO candidates and calculating their redshfit from a flood of spectra]. AB - In the present paper the author offers a method to search the QSO candidates and calculate their redshfit using their broad emission lines which are the most important character of quasars. It is hard to identify the lines in the quasar's spectra due to their redshifts distributing on a broad range. Spectra contain two components. One is continuum and the other is lines. The author uses a method of LFPS (low frequency points set) to build the continuum and detect the obvious emission lines, a method that can avoid the broad emission lines as a part of the continuum. The redshift can be calculated by comparing the extracted lines with the line table. The classification can be done with both emission lines and the redshift. For a better accurate rate to recognize the lines, this paper provides a method to estimate the level of the local noise. The method this paper used is independent of the flux calibration of the spectra. It can work for the spectra of the present LAMOST. PMID- 22097877 TI - [Galaxy/quasar classification based on nearest neighbor method]. AB - With the wide application of high-quality CCD in celestial spectrum imagery and the implementation of many large sky survey programs (e. g., Sloan Digital Sky Survey (SDSS), Two-degree-Field Galaxy Redshift Survey (2dF), Spectroscopic Survey Telescope (SST), Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) program and Large Synoptic Survey Telescope (LSST) program, etc.), celestial observational data are coming into the world like torrential rain. Therefore, to utilize them effectively and fully, research on automated processing methods for celestial data is imperative. In the present work, we investigated how to recognizing galaxies and quasars from spectra based on nearest neighbor method. Galaxies and quasars are extragalactic objects, they are far away from earth, and their spectra are usually contaminated by various noise. Therefore, it is a typical problem to recognize these two types of spectra in automatic spectra classification. Furthermore, the utilized method, nearest neighbor, is one of the most typical, classic, mature algorithms in pattern recognition and data mining, and often is used as a benchmark in developing novel algorithm. For applicability in practice, it is shown that the recognition ratio of nearest neighbor method (NN) is comparable to the best results reported in the literature based on more complicated methods, and the superiority of NN is that this method does not need to be trained, which is useful in incremental learning and parallel computation in mass spectral data processing. In conclusion, the results in this work are helpful for studying galaxies and quasars spectra classification. PMID- 22097878 TI - [One step method to design concave holographic grating for monochromator]. AB - The present paper put forward a new method, named one step method, to design concave holographic grating for a monochromator. This new method is simple and direct and easy to understand. Additionally, in this new method, we can control the whole aberrations of concave grating very well. Genetic algorithm was applied to optimize the objective function of this new method for its strong ability to search the extremum of nonlinear functions and a comparison was made between this new method and the classical method. The result shows that, for coma correction or astigmatism correction, the imaging properties of the concave grating designed by the new method is much better than the grating designed by the classical method. PMID- 22097880 TI - Bone segmentation applying rigid bone position and triple shadow check method based on RF data. AB - Noninvasive 3D reconstruction of a bone requires very accurate 2D navigated scans of bone. The use of brightness-mode ultrasound seems to be promising, if some 2D scans of bone are obtained in a fully automatic manner. This paper presents a rapid and fully automatic method for segmenting bone in a standard 2D ultrasound image (B-mode image). The algorithm focuses on segmenting bone in the B-mode image using RF data of the image. The article introduces the signal-processing scheme designed based on RF data to automatically segment bone in the B-mode image. The segmentation accuracy was assessed by performing various tests for this algorithm for various locations of the limbs of the human body. The algorithm was tested for 120 images taken at different locations of limbs of the human body. The sensitivity of these tests was calculated to be 0.99 and specificity was found to be 1. The suggested segmentation approach provides a reliable means of detecting bone in B-mode image. PMID- 22097879 TI - QM/MM analysis suggests that Alkaline Phosphatase (AP) and nucleotide pyrophosphatase/phosphodiesterase slightly tighten the transition state for phosphate diester hydrolysis relative to solution: implication for catalytic promiscuity in the AP superfamily. AB - Several members of the Alkaline Phosphatase (AP) superfamily exhibit a high level of catalytic proffciency and promiscuity in structurally similar active sites. A thorough characterization of the nature of transition state for different substrates in these enzymes is crucial for understanding the molecular mechanisms that govern those remarkable catalytic properties. In this work, we study the hydrolysis of a phosphate diester, MpNPP(-), in solution, two experimentally well characterized variants of AP (R166S AP, R166S/E322Y AP) and wild type Nucleotide pyrophosphatase/phosphodiesterase (NPP) by QM/MM calculations in which the QM method is an approximate density functional theory previously parametrized for phosphate hydrolysis (SCC-DFTBPR). The general agreements found between these calculations and available experimental data for both solution and enzymes support the use of SCC-DFTBPR/MM for a semiquantitative analysis of the catalytic mechanism and nature of transition state in AP and NPP. Although phosphate diesters are cognate substrates for NPP but promiscuous substrates for AP, the calculations suggest that their hydrolysis reactions catalyzed by AP and NPP feature similar synchronous transition states that are slightly tighter in nature compared to that in solution, due in part to the geometry of the bimetallic zinc motif. Therefore, this study provides the first direct computational support to the hypothesis that enzymes in the AP superfamily catalyze cognate and promiscuous substrates via similar transition states to those in solution. Our calculations do not support the finding of recent QM/MM studies by Lopez-Canut and co-workers, who suggested that the same diester substrate goes through a much looser transition state in NPP/AP than in solution, a result likely biased by the large structural distortion of the bimetallic zinc site in their simulations. Finally, our calculations for different phosphate diester orientations and phosphorothioate diesters highlight that the interpretation of thio-substitution experiments is not always straightforward. PMID- 22097881 TI - Hypoxia inducible factor-1alpha is involved in the neurodegeneration induced by isoflurane in the brain of neonatal rats. AB - More and more data show isoflurane, a commonly used volatile anesthetic has dual effects on neuron fate. However, the underlying mechanisms that can explain the apparent paradox are poorly understood. Hypoxia inducible factor (HIF)-1alpha, a transcription factor, has been found regulating both prosurvival and prodeath pathways in the CNS. Previously, we found that isoflurane can activate HIF-1alpha under normoxic conditions in vitro and HIF-1alpha has been found to be involved in the pre-conditioning effect of isoflurane in various organs. Here, we investigated whether HIF-1alpha is a contributing factor in the neurodegenration in rodent primary cultured neurons and in developing rat brain. Isoflurane dose dependently induced apoptotic neurodegeneration in neonatal rats as assessed by S100beta, cleaved caspase 3 and poly-(ADP-ribose) polymerase (PARP), respectively. Notably, isoflurane up-regulates HIF-1alpha protein levels in vivo and in vitro during induction of neurodegeneration. Likewise, isoflurane resulted in a significant elevation of cytosonic calcium levels in neuron cultures. Furthermore, knockdown of HIF-1alpha expression in cultured neurons attenuated isoflurane-induced neurotoxicity. Finally, Morris water maze (MWM) test showed neonatal exposure to isoflurane impaired juvenile learning and memory ability in rats. These findings indicate that HIF-1alpha is involved in the neurodegeneration induced by isoflurane in the brain of neonatal rats, suggesting HIF-1alpha may be a candidate for the dual effects of isoflurane on neuron fate. PMID- 22097882 TI - Enantioselective enolate protonation in sulfa-Michael addition to alpha substituted N-acryloyloxazolidin-2-ones with bifunctional organocatalyst. AB - Organocatalytic conjugate addition of thiols to alpha-substituted N acryloyloxazolidin-2-ones followed by asymmetric protonation has been studied in the presence of cinchona alkaloid derived thioureas. Both of the enantiomers are accessible with the same level of enantioselectivity using pseudoenantiomeric quinine/quinidine derived catalysts. The addition/protonation products have been converted to useful biologically active molecules. PMID- 22097884 TI - Severe lipoatrophy with insulin in type 1 diabetes. PMID- 22097883 TI - Radical-mediated enzymatic methylation: a tale of two SAMS. AB - Methylation is an essential and ubiquitous reaction that plays an important role in a wide range of biological processes. Most biological methylations use S adenosylmethionine (SAM) as the methyl donor and proceed via an S(N)2 displacement mechanism. However, researchers have discovered an increasing number of methylations that involve radical chemistry. The enzymes known to catalyze these reactions all belong to the radical SAM superfamily. This family of enzymes utilizes a specialized [4Fe-4S] cluster for reductive cleavage of SAM to yield a highly reactive 5'-deoxyadenosyl (dAdo) radical. Radical chemistry is then imposed on a variety of organic substrates, leading to a diverse array of transformations. Until recently, researchers had not fully understood how these enzymes employ radical chemistry to mediate a methyl transfer reaction. Sequence analyses reveal that the currently identified radical SAM methyltransferases (RSMTs) can be grouped into three classes, which appear distinct in protein architecture and mechanism. Class A RSMTs mainly include the rRNA methyltransferases RlmN and Cfr from various origins. As exemplified by Escherichia coli RlmN, these proteins have a single canonical radical SAM core domain that includes an (betaalpha)(6) partial barrel most similar to that of pyruvate formate lyase-activase. The exciting recent studies on RlmN and Cfr are beginning to provide insights into the intriguing chemistry of class A RSMTs. These enzymes utilize a methylene radical generated on a unique methylated cysteine residue. However, based on the variety of substrates used by the other classes of RSMTs, alternative mechanisms are likely to be discovered. Class B RSMTs contain a proposed N-terminal cobalamin binding domain in addition to a radical SAM domain at the C-terminus. This class of proteins methylates diverse substrates at inert sp(3) carbons, aromatic heterocycles, and phosphinates, possibly involving a cobalamin-mediated methyl transfer process. Class C RSMTs share significant sequence similarity with coproporphyrinogen III oxidase HemN. Despite methylating similar substrates (aromatic heterocycles), class C RSMTs likely employ a mechanism distinct from that of class A because two conserved cysteines that are required for class A are typically not found in class C RSMTs. Class A and class B enzymes probably share the use of two molecules of SAM: one to generate a dAdo radical and one to provide the methyl group to the substrate. In class A, a cysteine would act as a conduit of the methyl group whereas in class B cobalamin may serve this purpose. Currently no clues are available regarding the mechanism of class C RSMTs, but the sequence similarities between its members and HemN and the observation that HemN binds two SAM molecules suggest that class C enzymes could use two SAM molecules for catalysis. The diverse strategies for using two SAM molecules reflect the rich chemistry of radical-mediated methylation reactions and the remarkable versatility of the radical SAM superfamily. PMID- 22097885 TI - Introducing routine trial of labour after caesarean section in a second level hospital setting. AB - OBJECTIVE: We analysed the impact on caesarean section (CS) rate of introducing a routine trial of labour (TOL) for patients with a previous CS. STUDY DESIGN: During 2007 and 2008, we offered a TOL to all women with one previous CS planning to give birth in our hospital. The adherence to the procedure, success of vaginal delivery, overall CS rate, incidence of symptomatic uterine rupture and other complications were evaluated. Labour induction was allowed only using castor oil or Amniotomy. RESULTS: One hundred and ninety-four women were considered eligible for TOL. A total of 87.6% of them agreed to undergo the procedure (78.7% in the first year versus 95.2% in the second year, p < 0.05). Of these, 63.5% delivered successfully (42.3% in the first year versus 78.8% in the second year, p < 0.05); 10.6% underwent a primary CS because of failed spontaneous labour or failed labour induction and 25.9% a secondary CS during labour. The CS rate decreased significantly from 19.6% (in 2003-2006) to 14.9% (iN 2007-2008) (p < 0.05). One case of symptomatic uterine rupture occurred, while no difference for other complications was observed. CONCLUSIONS: The CS rate decreased dramatically through introducing a TOL programme for patients with one previous CS. The possibility of symptomatic uterine rupture should be however considered and patients adequately informed. PMID- 22097886 TI - The effects of methane and hydrogen gases produced by enteric bacteria on ileal motility and colonic transit time. AB - BACKGROUND: Gases produced by intestinal flora may modulate intestinal motor function in healthy individuals as well as those with functional bowel disease. Methane, produced by enteric bacteria in the human gut, is associated with slowed intestinal transit and constipation. The effects of hydrogen, another main gas produced by bacterial fermentation in the gut, on small bowel and colonic motor function remains unrecognized. Therefore, we set out to investigate whether intestinal gases including methane and hydrogen could influence the small bowel motility and colonic transit. METHODS: Guinea pig ileum was placed in the peristaltic bath with tension transducers attached to measure velocity and amplitude of peristaltic contraction before and after the infusion of control, hydrogen, and methane gases. Also, changes in the intraluminal pressures were monitored before and after the gas infusions. KEY RESULTS: Methane decreased peristaltic velocity and increased contraction amplitude significantly of guinea pig ileum (P < 0.05). The AUC of intraluminal pressure was significantly increased with methane in guinea pig ileum (P < 0.05). In a second experiment, guinea pig colon was placed in the peristaltic bath to measure transit time before and after control, hydrogen, methane, and methane-hydrogen mixture gas infusions. Hydrogen shortened colonic transit time by 47% in the proximal colon, and by 10% in the distal colon, when compared with baselines (P < 0.05). CONCLUSIONS & INFERENCES: Methane delayed ileal peristaltic conduction velocity by augmenting contractility. Hydrogen shortened colonic transit, and that effect was more prominent in the proximal colon than distal colon. PMID- 22097887 TI - Matching genetics with oceanography: directional gene flow in a Mediterranean fish species. AB - Genetic connectivity and geographic fragmentation are two opposing mechanisms determining the population structure of species. While the first homogenizes the genetic background across populations the second one allows their differentiation. Therefore, knowledge of processes affecting dispersal of marine organisms is crucial to understand their genetic distribution patterns and for the effective management of their populations. In this study, we use genetic analyses of eleven microsatellites in combination with oceanographic satellite and dispersal simulation data to determine distribution patterns for Serranus cabrilla, a ubiquitous demersal broadcast spawner, in the Mediterranean Sea. Pairwise population F(ST) values ranged between -0.003 and 0.135. Two genetically distinct clusters were identified, with a clear division located between the oceanographic discontinuities at the Ibiza Channel (IC) and the Almeria-Oran Front (AOF), revealing an admixed population in between. The Balearic Front (BF) also appeared to dictate population structure. Directional gene flow on the Spanish coast was observed as S. cabrilla dispersed from west to east over the AOF, from north to south on the IC and from south of the IC towards the Balearic Islands. Correlations between genetic and oceanographic data were highly significant. Seasonal changes in current patterns and the relationship between ocean circulation patterns and spawning season may also play an important role in population structure around oceanographic fronts. PMID- 22097888 TI - Effects of reactive oxygen species from activated leucocytes on human sperm motility, viability and morphology. AB - The accumulated data suggest that inflammation can increase the level of reactive oxygen species (ROS), which contribute to impaired sperm function and male infertility. Therefore, we propose that inflammation-mediated production of ROS in male and female reproductive tracts hinder sperm fertilisation. To test this hypothesis, phorbol myristate acetate (PMA) with polymorphonuclear leucocytes (PMNs) was applied to generate endogenous ROS. We evaluated the time-dependent effects of ROS on human sperm motility, viability and mitochondrial membrane potential (MMP). The results showed that after treatment with PMA and PMNs, the motility of human spermatozoa significantly decreased to 50% on Day 1 and 15% on Day 4 compared with that of the, respectively, negative controls (P = 0.012). The viability of human spermatozoa decreased on Day 4 of PMA + PMNs treatment (P = 0.028). The MMP of human spermatozoa significantly decreased from Day 2 to Day 4 in the PMA + PMN group compared with that of the controls (P = 0.019). Taken together, the 4-day cultivation approach provided an accurate evaluation of sperm quality, especially sperm motility and MMP. Our findings indicated that endogenous inflammation increased ROS levels, which might induce sperm oxidative damage. Additionally, sperm motility might be one of the earliest and most sensitive indicators of this damage. PMID- 22097889 TI - Association of tumor necrosis factor-alpha gene promoter polymorphism at sites 308 and -238 with non-alcoholic fatty liver disease: a meta-analysis. AB - BACKGROUND AND AIM: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD). The objective of this study was to quantitatively evaluate the association between tumor necrosis factor (TNF)-alpha gene promoter polymorphism at sites 308 and -238 and NAFLD susceptibility. METHODS: We performed an extensive search of relevant studies and made a meta-analysis, including eight studies with 837 NAFLD cases and 990 controls in the association between TNF-alpha -308 polymorphism and NAFLD; and seven studies with 771 cases and 787 controls in TNF alpha -238 polymorphism. RESULTS: The combined results showed that there was a significant difference in TNF-alpha-238 genotype distribution between NAFLD and control based on all studies (GA/AA vs GG [odds ratio = 2.06, 95% confidence interval = 1.58-2.69, P < 0.000,01]). However, the combined results based on all studies showed there was no evidence of association of TNF-alpha-308 genotype distribution between NAFLD cases and controls (GA/AA vs GG [odds ratio = 1.08, 95% confidence interval = 0.82-1.42, P = 0.60]). When stratifying for race, the significant results did not change materially compared with whole populations. CONCLUSION: This meta-analysis suggested that TNF-alpha gene promoter polymorphism at position -238 but not -308 might be a risk factor for NAFLD. PMID- 22097890 TI - Chemical and antioxidant properties of casein peptide and its glucose Maillard reaction products in fish oil-in-water emulsions. AB - Maillard reaction products (MRPs) were prepared by reacting casein peptides with different concentrations of glucose at 80 degrees C for up to 12 h. The chemical properties of MRPs and their effects on lipid oxidation in fish oil-in-water emulsions were investigated. Increasing browning development and absorbance in 294 nm in the MRPs caused an increase in DPPH radical scavenging, but a decrease in iron chelation, which could be related to the loss of free amino groups in the peptides. The MRPs produced with longer reaction time or higher glucose concentrations were less effective in inhibiting lipid oxidation in emulsions at pH 7.0 compared to casein peptides alone. However, the antioxidant activity of MRPs in emulsions at pH 3.0 was not decreased by prolonged heating. The bitterness of MRPs was less than that of the original casein peptides, and bitterness decreased with increasing heating time and glucose concentrations. Therefore, the Maillard reaction was a potential method to reduce the bitterness of casein peptides while not strongly decreasing their antioxidant activity. PMID- 22097891 TI - Immediate breast reconstruction and compliance with UK national cancer waiting targets: the University Hospital Birmingham experience. PMID- 22097893 TI - Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. AB - BACKGROUND: Nonalcoholic steatohepatitis (NASH), the most severe form of nonalcoholic fatty liver disease (NAFLD), is associated with inflammation and increased oxidative stress. The neutrophil/lymphocyte ratio (N/L) integrates information on the inflammatory milieu and physiological stress. AIMS: The aim of this study was to determine the utility of N/L ratio to predict the presence of NASH in patients with NAFLD. METHODS: Our cohort consisted of 101 consecutive patients undergoing liver biopsy for clinical suspicion of NAFLD. Patients were divided into two groups: NASH group (n = 50) and not NASH group (n = 51). The stage of fibrosis was measured using a 4-point scale. The total white cell count, neutrophil and lymphocyte counts were recorded, and the N/L ratio was calculated. RESULTS: The mean age was 49.5 (+/- 10.8) years and the mean BMI was 31.4 (+/- 4.9) kg/m(2) . Patients with NASH had a higher N/L ratio compared with patients with not NASH [2.5 (1.9-3.3) and 1.6 (1.2-2.0), respectively, P < 0.001]. The N/L ratio correlated with the NAFLD activity score and its individual components (steatosis, inflammation and ballooning P < 0.001). Patients with advanced fibrosis (F3-4) had an elevated N/L ratio [2.9 (2.0-3.9)] compared with patients with fibrosis stage 1-2 [1.8 (1.2-2.2)], P < 0.001. For each one-unit increase in N/L ratio, the likelihood of having NASH increased by 70% and the likelihood of having fibrosis increased by 50%. CONCLUSION: The N/L ratio is higher in patients with NASH and advanced fibrosis. This ratio can be used as a novel noninvasive marker to predict advanced disease. PMID- 22097894 TI - Tick saliva suppresses IFN signalling in dendritic cells upon Borrelia afzelii infection. AB - Type I interferons (IFN-alpha and IFN-beta) are crucial determinants of the host immune response and tick saliva modulates this response, thus facilitating the transmission of tickborne pathogens. The current study therefore examines the effect of Ixodes ricinus tick saliva on IFN-beta signalling in murine dendritic cells using lipopolysaccharide (LPS) and Borrelia afzelii spirochaetes as inducers. Activated dendritic cells secret IFN that activates Signal Transducer and Activator of Transcription 1 (STAT-1). Our results show that Borrelia-induced activation of STAT-1 was suppressed by tick saliva. As the amount of secreted IFN beta was not influenced by tick saliva, the results indicated that saliva affected the interferon pathway at the IFN receptor or downstream of it. By using recombinant IFN-beta, we show that tick saliva attenuates IFN-triggered STAT-1 activation. Tick saliva also inhibited LPS-induced IFN-beta production suggesting that saliva interferes with the activation of the pathway that mediates IFN-beta induction. Our data indicate that I. ricinus tick saliva may modulate the host immune response by attenuating the initial signal transduction pathway of type I IFN. PMID- 22097895 TI - DFNB49 is an important cause of non-syndromic deafness in Czech Roma patients but not in the general Czech population. AB - Due to endogamy, the Roma have a higher risk for autosomal recessive (AR) disorders. We used homozygosity mapping on single-nucleotide polymorphism chips in one Czech Roma consanguineous family with non-syndromic hearing loss (NSHL). The second largest homozygous region in a deaf patient was mapped to the previously reported DFNB49 region. The MARVELD2 gene was recently reported as a causal gene for NSHL DFNB49. Sequencing of the MARVELD2 gene revealed a previously reported homozygous mutation c.1331+2 T>C (IVS4 + 2 T>C) in the deaf child. Subsequently, the same mutation was found in two more Roma families from an additional 19 unrelated Czech Roma patients with deafness tested for the MARVELD2 gene. To explore the importance of MARVELD2 mutations and DFNB49 for the general Czech and Central European population with early hearing loss we also tested 40 unrelated Czech patients with AR NSHL. No pathogenic mutation in the MARVELD2 gene was found in a group of 40 Czech non-Roma patients. Mutations in the MARVELD2 gene seem to be a significant cause of early NSHL in Czech Roma and this gene should be tested in this group of patients after GJB2. PMID- 22097896 TI - Repair of rabbit osteochondral defects by an acellular technique with an ultrapurified alginate gel containing stromal cell-derived factor-1. AB - The objective of this study was to determine whether the local administration of stromal cell-derived factor-1 (SDF-1) using ultrapurified alginate gel (UPAL gel) could improve reparative tissues of osteochondral defects compared with those without treatment. For the investigation, a full-thickness osteochondral defect 4.5 mm in diameter and 3 mm in depth was created in the patella groove of the distal femur in rabbits. Local expression of SDF-1 protein was temporarily upregulated at 1 week after creating the osteochondral defect. The local administration of SDF-1 enhanced the migration of host cells, mainly bone marrow stromal cells (BMSCs), to the site of the osteochondral defect. In vitro cell migration assay supported this result. In the SDF-1 (UPAL gel containing SDF-1) treatment group, the histological scores and the compressive modulus of reparative tissues were significantly improved compared with the no-treatment and vehicle (UPAL gel without SDF-1) groups. On the other hand, SDF-1 did not influence the cellular proliferation and chondrogenesis of BMSCs. Based on the results obtained here, we speculate that SDF-1 enhances the reparative process of osteochondral injuries not through direct effects on the behavior of host cells, but through increased migration of host cells to the injured site. UPAL gel, as a vehicle material, may play an important role in chondrogenesis of recruited cells, mainly BMSCs. The cell-free approach with local administration of SDF-1 may be an effective strategy for developing a minimally invasive technique for cartilage tissue regeneration. PMID- 22097897 TI - Prevalence of melanocytic nevi in 8- to 10-year-old children in Southern Spain and analysis of associated factors. AB - BACKGROUND: There is a known relationship between melanocytic nevi (MN) and cutaneous melanoma. MN are related to genetic and environmental factors, and the latter appear to be more important in childhood. OBJECTIVES: To determine the prevalence of MN and its relationship with phenotypic traits and sun exposure habits in 8- to 10-year-old children. SUBJECTS AND METHODS: We performed a cross sectional study of 8- to 10-year-old primary school children in the city of Granada (Spain), gathering data on phenotypic traits, sun protection measures, sunburn frequency and the number and density of MN. RESULTS: We detected a mean of 19.38 MN per child, predominantly <2 mm in diameter. MN count was associated with low phototype, and was higher in boys vs. girls with low phototype. MN were more numerous with higher age. The largest number of MN of all sizes was detected in 10-year-old boys. MN were most frequently located on the torso and other sites intermittently exposed to sunlight. CONCLUSIONS: A higher MN count is associated with lower phototype (blonde hair and fair skin) and higher age. The mean number of MN, including those of smaller size (<2 mm), was elevated in our series, especially on intermittently exposed sites. PMID- 22097898 TI - Long-term outcome of primary non-responders to tenofovir therapy in HIV/HBV-co infected patients: impact of HBV genotype G. AB - AIM: To evaluate the early virological response (EVR) to combined tenofovir lamivudine or emtricitabine regimen in HBV/HIV-co-infected patients and the long term efficacy of tenofovir. METHODS: In this retrospective monocentric study, among the 166 HIV/HBV-co-infected patients regularly followed from 2003 to 2008 at Bichat Claude Bernard Hospital, 61 patients had received, either de novo combination therapy with tenofovir and lamivudine or emtricitabine (group I, n = 15) or add-on tenofovir to lamivudine therapy (group II, n = 46). The HBV polymerase region was sequenced and analysed for all patients with available samples. RESULTS: All 15 group I patients achieved EVR vs 32 (82%) of group II patients (P = 0.15). Seven adherent group II patients met criteria for primary non-response, but achieved delayed response (DR) to therapy. In these seven patients, when compared with the 39 group II patients, there was a trend to longer duration of lamivudine pre-treatment and to higher rate of lamivudine resistant mutants; and HBV genotype-G proportion was higher (P = 0.026). No virological breakthrough occurred after a median of 46 months follow up. CONCLUSION: In these HBV/HIV-co-infected patients, first-line HBV therapy with tenofovir and emtricitabine or lamivudine was associated with EVR. However, DR to tenofovir was observed in 15% of patients who added tenofovir to lamivudine therapy, of whom four of seven (57%) had genotype G-HBV infection. No resistance was evidenced after 46 months of therapy even in patients with DR to tenofovir. At last, a good renal safety profile of TDF was observed after a median follow-up of 4 years of therapy. PMID- 22097899 TI - Fatigue-induced increase in intracortical communication between mid/anterior insular and motor cortex during cycling exercise. AB - In the present study, intracortical communication between mid/anterior insular and motor cortex was investigated during a fatiguing cycling exercise. From 16 healthy male subjects performing a constant-load test at 60% peak oxygen consumption (VO(2peak)) until volitional exhaustion, electroencephalography data were analysed during repetitive, artefact-free periods of 1-min duration. To quantify fatigue-induced intracortical communication, mean intra-hemispheric lagged phase synchronization between mid/anterior insular and motor cortex was calculated: (i) at the beginning of cycling; (ii) at the end of cycling; and (iii) during recovery cycling. Results revealed significantly increased lagged phase synchronization at the end of cycling, which returned to baseline during recovery cycling after subjects' cessation of exercise. Following previous imaging studies reporting the mid/anterior insular cortex as an essential instance processing a variety of sensory stimuli and signalling forthcoming physiological threat, our results provide further evidence that during a fatiguing exercise this structure might not only integrate and evaluate sensory information from the periphery, but also act in communication with the motor cortex. To the best of our knowledge, this is the first study to empirically demonstrate that muscle fatigue leads to changes in interaction between structures of a brain's neural network. PMID- 22097900 TI - Hydration of formate and acetate ions by dielectric relaxation spectroscopy. AB - Dielectric relaxation (DR) spectra have been measured for aqueous solutions of sodium formate (NaOFm) and sodium acetate (NaOAc) over a wide range of frequencies (0.2 <= nu/GHz <= 89) up to solute concentrations c is less or approximately equal to 3.2 M and is less or approximately equal to 3.7 M, respectively, at 25 degrees C. Measurements were also made on NaOAc(aq) at 15 <= T/ degrees C <= 35. In addition to the usual dominant bulk-water relaxation process at ~20 GHz, one or two further relaxation modes were detected. One process, centered at ~8 GHz and observed for both NaOFm(aq) and NaOAc(aq), was attributed to the presence of slow water in the hydration shells of the anions. A lower-frequency process at ~0.6 GHz, observed only for NaOAc(aq) at c is less or approximately equal to 1 M, was thought to be due to the presence of very small concentrations of ion pairs. Detailed analysis of the spectra indicated that very few (<2 per anion) water molecules were irrotationally bound (frozen) on the DR time scale. Nevertheless, both anions are strongly hydrated, as evidenced by the significant amounts of slow water detected. Such H(2)O molecules with reduced dynamics result from two distinct effects. The first is the relatively strong hydrophilic interaction of water with the -COO(-) moiety, which is similar for the two anions and little affected by increasing solute concentration. The second (for OAc(-) only) is the hydrophobic hydration of the -CH(3) group, which is fragile, decreasing markedly with increasing solute concentration and temperature. The activation parameters for bulk-water relaxation in NaOAc(aq) indicated a breakdown of the bulk water structure at high solute concentrations. PMID- 22097903 TI - Circadian clocks and drug delivery systems: impact and opportunities in chronotherapeutics. AB - Chronotherapeutics aims at the adjustment of treatments to ~ 24 h rhythms, which result from the moderation of most biological functions by the circadian timing system (CTS). The integration of CTS-related knowledge in drug delivery concepts challenges most current views, where steady-state constant drug levels are synonymous to enhanced tolerability and efficacy. In contrast, robust molecular clocks rhythmically control Phase I, II and III drug metabolism, as well as pharmacodynamics. Thus, circadian timing of medications predictably modifies drug tolerability and/or efficacy up to several-fold in rodents, as well as in patients. Optimal dosing times indeed complement the recommendations for optimal doses of glucocorticoids, NSAIDs, bronchodilators and so on. Clinically-driven in vitro and in silico circadian data now provide mechanistic insights for the effective translation of chronotherapeutic delivery, especially for cancer therapies. Programmable-in-time electronic or polymeric drug delivery systems are being used for improving health in patients with cancer or rheumatoid diseases, respectively. Current research aims at the optimization of circadian amplitude and phase of drug delivery according to CTS biomarkers. Intelligent drug delivery systems could then integrate the critical rhythmic information stemming from the individual patient and achieve a critical leap forward in the safe administration of potentially toxic therapeutic agents. PMID- 22097901 TI - Overnight changes in waking auditory evoked potential amplitude reflect altered sleep homeostasis in major depression. AB - OBJECTIVE: Sleep homeostasis is altered in major depressive disorder (MDD). Pre- to postsleep decline in waking auditory evoked potential (AEP) amplitude has been correlated with sleep slow wave activity (SWA), suggesting that overnight changes in waking AEP amplitude are homeostatically regulated in healthy individuals. This study investigated whether the overnight change in waking AEP amplitude and its relation to SWA is altered in MDD. METHOD: Using 256-channel high-density electroencephalography, all-night sleep polysomnography and single-tone waking AEPs pre- and postsleep were collected in 15 healthy controls (HC) and 15 non medicated individuals with MDD. RESULTS: N1 and P2 amplitudes of the waking AEP declined after sleep in the HC group, but not in MDD. The reduction in N1 amplitude also correlated with fronto-central SWA in the HC group, but a comparable relationship was not found in MDD, despite equivalent SWA between groups. No pre- to postsleep differences were found for N1 or P2 latencies in either group. These findings were not confounded by varying levels of alertness or differences in sleep variables between groups. CONCLUSION: MDD involves altered sleep homeostasis as measured by the overnight change in waking AEP amplitude. Future research is required to determine the clinical implications of these findings. PMID- 22097904 TI - Advanced methodologies to formulate nanotheragnostic agents for combined drug delivery and imaging. AB - INTRODUCTION: Recent advances in nanoparticle synthesis engineering have made it possible to combine disease diagnosis and therapy. This progress could help to open the door to 'personalized' medicines. AREAS COVERED: This review highlights the significant applications of theragnostic nanoparticles in therapy. The basic elements to be included in the formulation of theragnostic nanotools are briefly compiled and explained. Special attention is given to the analysis of current formulation strategies from case studies in the literature published after 2000 for simultaneous selective disease imaging and efficient image-guided drug (gene) delivery. This contribution provides a systematic overview of important features in the formulation of theragnostic nanoparticulate systems. Special insight is given to the introduction of passive and active targeting concepts in the engineering of such multifunctional nanoplatforms to gain control of their biological fate. EXPERT OPINION: Theragnostic nanotechnologies will optimize the way of delivering therapeutic and imaging molecules to disease sites; as a consequence, combined selective diagnosis and effective pharmacotherapy could be used in unison to combat severe diseases. Nanotoxicity investigations, which illustrate the risks of toxicity/immunogenicity associated with the use of such nanoplatforms, will determine their introduction into the clinic. PMID- 22097902 TI - Differential roles of cysteine residues in the cellular trafficking, dimerization, and function of the high-density lipoprotein receptor, SR-BI. AB - The scavenger receptor, class B, type I (SR-BI) binds high-density lipoprotein (HDL) and mediates selective delivery of cholesteryl esters (CEs) to the liver and steroidogenic cells of the adrenal glands and gonads. Although it is clear that the large extracellular domain (ECD) of SR-BI binds HDL, the role of ECD in the selective HDL-CE transport remains poorly understood. In this study, we used a combination of mutational and chemical approaches to systematically evaluate the contribution of cysteine residues, especially six cysteine residues of ECD, in SR-BI-mediated selective HDL-CE uptake, intracellular trafficking, and SR-BI dimerization. Pretreatment of SR-BI-overexpressing COS-7 cells with a disulfide (S-S) bond reducing agent, beta-mercaptoethanol (100 mM) or dithiothreitol (DTT) (10 mM), modestly but significantly impaired SR-BI-mediated selective HDL-CE uptake. Treatment of SR-BI-overexpressing COS-7 cells with the optimal doses of membrane permeant alkyl methanethiosulfonate (MTS) reagents, positively charged MTSEA or neutral MMTS, that specifically react with the free sulfhydryl group of cysteine reduced the rate of SR-BI-mediated selective HDL-CE uptake, indicating that certain intracellular free cysteine residues may also be critically involved in the selective cholesterol transport process. In contrast, use of membrane impermeant MTS reagent, positively charged MTSET and negatively charged MTSES, showed no such effect. Next, the importance of eight cysteine residues in SR-BI expression, cell surface expression, dimer formation, and selective HDL-derived CE transport was evaluated. These cysteine residues were replaced either singly or in pairs with serine, and the mutant SR-BIs were expressed in either COS-7 or CHO cells. Four mutations, C280S, C321S, C323S, and C334S, of the ECD, either singly or in various pair combinations, resulted in significant decreases in SR BI (HDL) binding activity, selective CE uptake, and trafficking to the cell surface. Surprisingly, we found that mutation of the two remaining cysteine residues, C251 and C384 of the ECD, had no effect on either SR-BI expression or function. Other cysteine mutations and substitutions were also without effect. Western blot data indicated that single and double mutations at C280, C321, C323, and C334 residues strongly favor dimer formation. However, they are rendered nonfunctional presumably because of mutation-induced formation of aberrant disulfide linkages resulting in inhibition of optimal HDL binding and, thus, selective HDL-CE uptake. These results provide novel insights into the functional role of four cysteine residues, C280, C321, C323, and C334, of the SR-BI ECD in SR-BI expression and trafficking to the cell surface, its dimerization, and associated selective CE transport function. PMID- 22097905 TI - Quality by design (QbD) approaches for the compression step of tableting. AB - INTRODUCTION: Although tableting is one of the most commonly used processes in drug manufacturing, the tablet formation process is still not fully understood, nor can it be fully controlled. AREAS COVERED: In this paper, recent approaches to correlate tablet mechanical properties with process parameters are discussed, covering (mainly) the last 5 years. These approaches are the basis for a future of rational formulation strategies, which may lead to optimum tablet properties within a shorter timescale, in contrast to the present empirical approach. The reader will on one hand gain an insight into current parameterization of the tableting process and evaluation strategies and on the other hand will gain an impression of the difficulties connected to the interpretation of a physically complex process and its impact on predictive modeling. EXPERT OPINION: The main consolidated findings are that even when using multivariate statistical approaches, it cannot be expected to find a global evaluation method that fully explains the mechanism of tableting, but that careful sequential evaluation is required. For further improvement, there is a need to use more complex models and alternative technologies, in order to increase both tablet quality and productivity. PMID- 22097906 TI - Spray granulation for drug formulation. AB - INTRODUCTION: Granulation is a key unit process in the production of pharmaceutical solid dosage forms and involves the agglomeration of fine particles with the aid of a binding agent. Fluidized bed granulation, a classic example of spray granulation, is a technique of particle agglomeration brought about by the spray addition of the binding liquid onto a stationary bed of powder particles that is transformed to a fluid-like state by the passage of air through it. AREAS COVERED: The basic working principles, equipment set-up, advantages and challenges of fluidized bed granulation are introduced in this review. This is followed by an overview of the formulation and process-related variables affecting granulation performance. Technological advances, particularly in the application of process analytical tools, in the field of fluidized bed granulation research are also discussed. EXPERT OPINION: Fluidized bed granulation is a popular technique for pharmaceutical production, as it is a highly economical and efficient one-pot process. The research and development of process analytical technologies (PAT) has allowed greater process understanding and control to be achieved, even for the lesser known fluidized bed techniques, such as bottom spray and fluidized hot melt granulation. In view of its consistent mixing, as well as continuous and concurrent wetting and drying occurring throughout processing, fluidized bed granulation shows great potential for continuous production although more research is required to fully implement, validate and integrate the PAT tools in a production line. PMID- 22097907 TI - Clinical trials of intranasal delivery for treating neurological disorders--a critical review. AB - INTRODUCTION: The intranasal delivery of therapeutics to the brain has achieved great success in preclinical studies. These findings are important because there are many neurological disorders without feasible treatments, due to a lack of effective drug delivery methods to the brain. Translating such intranasal delivery strategies from bench to bedside is an important step for curing these neurological diseases. AREAS COVERED: This review summarizes recent clinical trials that have investigated the intranasal delivery of drugs to the brain to treat neurological disorders and their potential mechanisms of action. In addition, the potential opportunities as well as challenges of intranasal delivery in clinical trials are discussed. EXPERT OPINION: The intranasal delivery of drugs to the brain is a novel method with great potential, and it may provide an extraordinary approach to overcome the existing barriers of drug delivery for treating some neurological disorders. Intranasal delivery of central nervous system therapeutics has shown promise in several clinical trials, which demonstrates both the need and importance of further research. PMID- 22097908 TI - Prediction of lower extremities' movement by angle-angle diagrams and neural networks. AB - In contemporary science, the analysis of human walking is extensively used. The prediction of leg motion, as well as rehabilitation, can be usable for orthosis and prosthesis programing. Our work is focused on predicting of human walking by angle-angle diagrams, also called cyclograms. The applications of cyclograms in conjunction with artificial intelligence offers wide area of applications in medicine. But until now, this approach has not been studied or applied in practice. PMID- 22097909 TI - Mathematical modelling of ciliary movement mechanism. AB - The main purpose of the paper was to present a new approach to the mathematical modelling of ciliary movements. This approach is based on the solution of the inverse problem of the dynamics, which is described by Lagrange's equations for the system of successively hinged rigid rods. In this case, as is well known, the generalized forces may be found as the time functions. It is proposed to represent these functions by the functions of generalized coordinates and velocities and also of the model parameters, whose values are determined as a solution of the parametric optimization problem. Besides, a special algorithm of ciliary movement control was elaborated. This algorithm is based on the hypothesis of variation of the equilibrium positions for cilia during one cycle of beating. The numerical results are in a good agreement with the cilia movements observed in Paramecium multimicronucleatum. PMID- 22097910 TI - Generation of singlet oxygen by the glyoxal-peroxynitrite system. AB - Diacetyl, methylglyoxal, and glyoxal are alpha-dicarbonyl catabolites prone to nucleophilic additions of amino groups of proteins and nucleobases, thereby triggering adverse biological responses. Because of their electrophilicity, in aqueous medium, they exist in a phosphate-catalyzed dynamic equilibrium with their hydrate forms. Diacetyl and methylglyoxal can be attacked by peroxynitrite (k(2) ~ 1.0 * 10(4) M(-1) s(-1) and k(2) ~ 1.0 * 10(5) M(-1) s(-1), respectively), a potent biological nucleophile and oxidant, yielding the acetyl radical from the homolysis of peroxynitrosocarbonyl adducts, and acetate or formate ions, respectively. We report here that glyoxal also reacts with peroxynitrite, yielding formate ion at rates at least 1 order of magnitude greater than does methylglyoxal. A triplet EPR signal (1:2:1; a(H) = 0.78 mT) attributable to hydrated formyl radical was detected by direct flow experiments. In the presence of the spin trap 2-methyl-2-nitrosopropane, the EPR spectrum displays the di-tert-butyl nitroxide signal, another signal assignable to the spin trapping adduct with hydrogen radical (a(N) = a(H) = 1.44 mT), probably formed from formyl radical decarbonylation, and a third EPR signal assignable to the formyl radical adduct of the spin trap (a(N) = 0.71 mT and a(H) = 0.14 mT). The novelty here is the detection of singlet oxygen ((1)Delta(g)) monomol light emission at 1270 nm during the reaction, probably formed by subsequent dioxygen addition to formyl radical and a Russell reaction of nascent formylperoxyl radicals. Accordingly, the near-infrared emission increases upon raising the peroxynitrite concentration in D(2)O buffer and is suppressed upon addition of O(2) ((1)Delta(g)) quenchers (NaN(3), l-His, H(2)O). Unequivocal evidence of O(2) ((1)Delta(g)) generation was also obtained by chemical trapping of (18)O(2) ((1)Delta(g)) with anthracene-9,10-divinylsulfonate, using HPLC/MS/MS for detection of the corresponding 9,10-endoperoxide derivative. Our studies add insights into the molecular events underlying nitrosative, oxidative, and carbonyl stress in inflammatory processes and aging-associated maladies. PMID- 22097911 TI - Exploratory study on the effect of osteoactivin on bone formation in the rat critical-size calvarial defect model. AB - BACKGROUND AND OBJECTIVE: Osteoactivin is a novel glycoprotein shown to exhibit an important role in regulating osteoblast differentiation and function. The aim of the present study was to evaluate the potential of osteoactivin to support bone regeneration using an established defect model. MATERIAL AND METHODS: Critical-size, 8-mm-diameter through-and-through calvarial osteotomy defects were created in 60 adult male Sprague-Dawley rats. Test animals received 0.1 mL of osteoactivin in phosphate-buffered saline (50 MUg/mL) soak-loaded onto an absorbable collagen sponge. Controls received 0.1 mL of phosphate-buffered saline soak-loaded onto the absorbable collagen sponge or no further intervention (sham surgery). The animals were euthanized 2 and 4 wk after treatment and histometric analyses were performed. RESULTS: The absorbable collagen sponge control (mean +/ standard deviation: 40.9 +/- 26.9%) showed borderline significant greater bone fill compared with sham-surgery (22.9 +/- 15.8%; p = 0.10) and osteoactivin (20.2 +/- 11.8%; p = 0.07) treatments at 2 wk. In contrast, osteoactivin (84.7 +/- 15.8%) showed significantly greater bone fill than sham-surgery (28.4 +/- 9.6%; p < 0.001) and absorbable collagen sponge (41.8 +/- 22.1%; p < 0.001) at 4 wk. No animals receiving sham-surgery or absorbable collagen sponge exhibited complete bone fill at 4 wk while 70% of the animals receiving osteoactivin showed complete bone fill. CONCLUSION: Osteoactivin demonstrates a significant potential to support bone regeneration/formation. Studies using discriminating large animal models are necessary to explore clinical application for periodontal and craniofacial indications. PMID- 22097913 TI - Material aspects of growth plate modelling using Carter's and Stokes's approaches. AB - Growth plate, named also as physis, is the anatomical structure responsible for the bone growth. Apart from numerous biological and biochemical factors, biomechanics has also strong influence on its functioning. Loadings acting on the bone element during its development can change (increase or decrease) the velocity of growth. This way mechanobiological processes influence the skeletal development. Several theories try to describe the relationship between loadings acting on the physis and biological processes leading to bone growth and development. Unfortunately, some serious discrepancies exist between them. Additionally, difficulties occur during the modelling of the growth plate activity, which results from the problems in determining material parameters of the particular physis component. The aim of the study was to analyse the influence of material properties of particular parts of the physis on biomechanical conditions of the bone growth. Two concepts, based on the Carter's and Stokes's approaches, were applied to estimate the biomechanical stimulation of the bone growth occurring within the physis volume. Results of the numerical simulations show that due to inhomogeneity of the physis structure, the complex 3 D stress state occurs within the growth plate even in the case of uniform axial pressure acting on its surface. The value of the cartilage Poisson's ratio has a significant influence on the biomechanics of the growth plate activity estimated using both theories. Carter's model is additionally very sensitive to its dilatational parameter. Both methods lead to non-uniform patterns of mechanical stimulation of the bone growth within the volume of the cartilage. The differences in the stiffness between cartilaginous and bone parts of the growth plate are of fundamental importance for such phenomenon. PMID- 22097912 TI - Effects of oxygen on zonal marker expression in human articular chondrocytes. AB - Articular cartilage is organized in depth zones with phenotypically distinct subpopulations of chondrocytes that are exposed to different oxygen tensions. Despite growing evidence of the critical role for oxygen in chondrogenesis, little is known about its effect on chondrocytes from different zones. This study evaluates zonal marker expression of human articular chondrocytes from different zones under various oxygen tensions. Chondrocytes isolated from full-thickness, superficial, and middle/deep cartilage from knee replacement surgeries were expanded and redifferentiated under hypoxic (5% O(2)) or normoxic (20% O(2)) conditions. Differentiation under hypoxia increased expression of hypoxia inducible factors 1alpha and 2alpha and accumulation of extracellular matrix, particularly in middle/deep chondrocytes, and favored re-expression of proteoglycan 4 by superficial chondrocytes compared with middle/deep cells. Zone dependent expression of clusterin varied with culture duration. These results demonstrate that zonal chondrocytes retain important phenotypic differences during in vitro cultivation, and that these characteristics can be improved by altering the oxygen environment. However, transcript levels for pleiotrophin, cartilage intermediate layer protein, and collagen type X were similar between zones, challenging their reliability as zonal markers for tissue-engineered cartilage from osteoarthritis patients. Key factors including oxygen tension and cell source should be considered to prescribe zone-specific properties to tissue engineered cartilage. PMID- 22097918 TI - Modifications of stearidonic acid soybean oil by enzymatic acidolysis for the production of human milk fat analogues. AB - Structured lipids (SLs) from stearidonic acid (SDA) soybean oil pre-enriched with palmitic acid (PA) at the sn-2 position with Novozym 435 (NSL) or Lipozyme TL IM (LSL) from previous research were further enriched with gamma-linolenic acid (GLA) or docosahexaenoic acid (DHA). Small-scale acidolysis reactions with Lipozyme TL IM were performed to determine the optimal reaction conditions as 1:1 substrate mole ratio of NSL or LSL to free DHA at 65 degrees C for 24 h and a 1:0.5 substrate mole ratio of NSL or LSL to free GLA at 65 degrees C for 12 h. Optimized SL products were scaled up in a 1 L stir-batch reactor, and the resulting SLs of NSL:DHA (NDHA), LSL:DHA (LDHA), NSL:GLA (NGLA), and LSL:GLA (LGLA) were chemically and physically characterized. The SLs contained >54% PA at the sn-2 position with GLA >8% for the GLA SLs and DHA >10% for the DHA SLs. The oxidative stabilities of the SLs were increased by the addition of 200 ppm TBHQ, with NGLA being more stable due to higher tocopherol content than the other SLs. The melting and crystallization profiles did not differ between the DHA SLs or the GLA SLs. The triacylglycerol (TAG) species were similar for the GLA SLs but differed between the DHA SLs, with tripalmitin being the major TAG species in all SLs. PMID- 22097919 TI - Expression of oxytocin receptor in diabetic rat penis. AB - Oxytocin receptor (OTR) expressed in the rat penis and mediated the contractility of the corpus cavernosum smooth muscle both in vitro and in vivo, and OTR could maintain penile detumescence; however, the expression of OTR in diabetic rat penis remains unknown. In the present study, we investigated the expression of OTR in diabetic rat penis. The experimental rats were randomly divided into control group and STZ-diabetic rats group. The expressions of mRNA and protein were examined by real-time quantitative PCR, Western blotting and immunohistochemistry respectively. Erectile function was evaluated by measuring intracavernous pressure following electrostimulation of the cavernous nerves. mRNA and protein expression of OTR significantly increased in diabetic rats group compared with the control group. Erectile function of diabetic rats group significantly decreased compared with the control group. Our data showed that the expression of OTR significantly increased in diabetic rats group and OTR may involve in the development of diabetic erectile dysfunction. PMID- 22097920 TI - Slow gallbladder emptying reverts to normal but small intestinal transit of a physiological meal remains slow in celiac patients during gluten-free diet. AB - BACKGROUND: Alterations of small intestinal transit and gallbladder (GB) motility have been reported in celiac disease (CD) in studies involving, in most cases, non-physiological experimental conditions and artificial stimuli to motility. Our aims were to quantitate non-invasively small intestinal transit time and GB emptying during administration of a physiological and palatable solid meal, and to assess the effect of gluten-free diet (GFD). METHODS: We simultaneously measured mouth-to-cecum transit time (MCTT) using a validated H(2) breath test, and GB motility using ultrasonography. We studied CD patients before (n = 19) and during (n = 14) GFD, and healthy volunteers (n = 24) following administration of a physiological solid meal (Kcal 539). KEY RESULTS: Mouth-to-cecum transit time was more prolonged in CD (mean +/- SEM: 235 +/- 96 min) than in controls (169 +/- 65 min, P = 0.0039). The GB fasting volume and postprandial residual volume were significantly higher in CD than in controls, and GB emptying constant was slower in CD than in controls. During GFD, GB emptying reverted to normal, but MCTT remained unchanged (229 +/- 69 min) and more prolonged in CD than in controls (P = 0.0139). During GFD, duodenal infiltration with lymphocytes and mast cells persisted higher than that in controls, and the number of mast cells lying in proximity of nervous endings did not change. CONCLUSIONS & INFERENCES: Slow postprandial MCTT in response to a physiological meal does not revert to normal during GFD, an effect mirroring incomplete histopathologic recovery. PMID- 22097921 TI - Simplistic partially limiting surgical guide for flapless implant placement: a case report. AB - The accurate positioning of implant in bone is important in order to meet the biological, esthetic, and biomechanical requirements of the prosthesis. This becomes crucial in flapless implant placement. The combination of bone sounding and use of a surgical guide will allow precise placement of a dental implant, abutment, and provisional restoration in a minimally invasive manner. A technique to transfer the diagnostic information to the surgical guide is described in this report. The chief advantage of the procedure is the ability to apply flapless implant placement surgery and immediate loading. PMID- 22097922 TI - A trimeric supercomplex of the oxygen-tolerant membrane-bound [NiFe]-hydrogenase from Ralstonia eutropha H16. AB - The oxygen-tolerant membrane-bound [NiFe]-hydrogenase (MBH) from Ralstonia eutropha H16 consists of three subunits. The large subunit HoxG carries the [NiFe] active site, and the small subunit HoxK contains three [FeS] clusters. Both subunits form the so-called hydrogenase module, which is oriented toward the periplasm. Membrane association is established by a membrane-integral cytochrome b subunit (HoxZ) that transfers the electrons from the hydrogenase module to the respiratory chain. So far, it was not possible to isolate the MBH in its native heterotrimeric state due to the loss of HoxZ during the process of protein solubilization. By using the very mild detergent digitonin, we were successful in isolating the MBH hydrogenase module in complex with the cytochrome b. H(2) dependent reduction of the two HoxZ-stemming heme centers demonstrated that the hydrogenase module is productively connected to the cytochrome b. Further investigation provided evidence that the MBH exists in the membrane as a high molecular mass complex consisting of three heterotrimeric units. The lipids phosphatidylethanolamine and phosphatidylglycerol were identified to play a role in the interaction of the hydrogenase module with the cytochrome b subunit. PMID- 22097924 TI - Primary cicatricial alopecia: recent advances in understanding and management. AB - Primary cicatricial alopecias (PCA) are a rare group of disorders, in which the hair follicle is the main target of destructive inflammation resulting in irreversible hair loss with scarring of affected lesions. The most typical clinical manifestation of PCA is the loss of visible follicular ostia. The histopathological hallmark of a fully developed lesion is the replacement of the hair follicle structure by fibrous tissue. PCA could share similar clinical manifestations and eventually lead to "burn-out" alopecia. Some subsets are hardly distinguishable histopathologically and the mechanisms that elicit such a destructive reaction have not been fully elucidated. Thus, the management of PCA represents one of the most challenging clinical problems for dermatologists. The aim of this review is to provide a concise and comprehensive summary of recent advances in PCA management, especially focusing on novel methodologies to aid diagnosis, and updates on our understanding of the etiopathogenesis. Dermoscopy, a new pathological preparation technique and direct immunofluorescence analysis enable more accurate clinicopathological diagnosis of PCA. Microarray analysis may be beneficial to distinguish PCA subtypes. Currently suggested mechanisms underlying PCA include loss of immune protection of stem cells, impaired stem cell self-maintenance, enhanced autoimmunity by pro-inflammatory cytokines and environmental/genetic predispositions. Interestingly, recent data indicates the association between lipid metabolism dysregulation and PCA development, implying an important role of the sebaceous gland dysfunction in the etiopathogenesis. Based on that hypothesis and observations, novel therapeutic approaches have been proposed, including the use of peroxisome proliferator-activated receptor-gamma agonist for lichen planopilaris. PMID- 22097923 TI - Circulating anti-angiogenic factors during hypertensive pregnancy and increased risk of respiratory distress syndrome in preterm neonates. AB - OBJECTIVE: To test the hypothesis that high circulating concentrations of maternal anti-angiogenic factors are associated with increased risk of respiratory distress syndrome (RDS). STUDY DESIGN: This is a nested case-control study of nulliparous women who delivered less than 37 weeks of gestation within the Calcium for Preeclampsia Prevention (CPEP) trial. The study included 116 women with preeclampsia or gestational hypertension and 323 normotensive controls. Soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) in maternal serum were measured at 21-32 weeks of gestation. RESULTS: Preterm infants born to hypertensive mothers were more likely to develop RDS (22.5% vs. 20.9%, p = 0.03). After adjustment for gestational age at delivery, the odds ratio for the relationship between hypertension in pregnancy and RDS was 2.18 (95% CI 1.08-4.39). In hypertensive pregnancies women whose infants developed RDS had significantly higher circulating mean sFlt1 levels during midpregnancy (21-32 weeks of gestation) even after adjustment for gestational age at delivery (21,516 pg/mL vs. 7,000 pg/mL, p = 0.01). CONCLUSIONS: Preterm preeclampsia and gestational hypertension, characterized by high circulating levels of sFlt1, are associated with a twofold increased risk of RDS in infants delivered before 37 weeks. Among women with these hypertensive pregnancies circulating sFlt1 concentrations during midpregnancy were substantially higher in women whose infants developed RDS. PMID- 22097925 TI - Investigational NMDA receptor modulators for depression. AB - INTRODUCTION: With regards to depression, the role of N-methyl-D-aspartate receptor (NMDA) was pursued many years ago, mainly in the form of preclinical studies. Since then, there have been several clinical data in the literature indicating the efficacy of NMDA receptor antagonists of either stand-alone or as an adjunct therapy in depression and depression-related diseases. AREAS COVERED: The present review focuses on clinical data of well-known and recently discovered NMDA receptor antagonists/modulators and their mechanisms of action. EXPERT OPINION: Several NMDA receptor modulators have been tested in both human and animal studies to examine their potential antidepressant activity. Most of the compounds that exhibited beneficial properties in the animal tests and models of depression either have never been tested or did not show efficacy in humans. For some of them, such as ketamine, where a consistently reproducible antidepressant effect was found, clinical use is limited by a variety of adverse effects. However, ketamine has become a standard tool for identifying the biological factors associated with rapid antidepressant action and, as such, is a novel target for the development of new therapeutics. PMID- 22097926 TI - Evolving concepts in primary sclerosing cholangitis. AB - Patients suffering from primary sclerosing cholangitis (PSC) show considerable differences regarding clinical manifestations (i.e. large duct versus small-duct PSC, presence or absence of concomitant inflammatory bowel disease), disease progression, risk for malignancy and response to therapy, raising the question whether PSC may represent a mixed bag of diseases of different aetiologies. The growing list of secondary causes and diseases 'mimicking' or even overlapping with PSC (e.g. IgG4-associated sclerosing cholangitis), which frequently causes problems in clear-cut discrimination from classic PSC and the emerging knowledge about potential disease modifier genes (e.g. variants of CFTR, TGR5 and MDR3) support such a conceptual view. In addition, PSC in children differs significantly from PSC in adults in several aspects resulting in distinct therapeutic concepts. From a clinical perspective, appropriate categorization and careful differential diagnosis are essential for the management of concerned patients. Therefore, the aim of the current review is to summarize current and evolving pathophysiological concepts and to provide up-to-date perspectives including future treatment strategies for PSC. PMID- 22097927 TI - Uric and 1-methyluric acids: metabolic wastes or antiradical protectors? AB - The reactions of uric and 1-methyluric acids in nonpolar environments, as well as those of the corresponding urate anions in aqueous solution, with (*)OH, (*)OCH(3), (*)OOH, and (*)OOCH(3) have been studied using the density functional theory. Different mechanisms of reactions have been taken into account, and their relative importance on the antiradical activity of these compounds is analyzed. Both uric and methyluric acids are better scavengers in aqueous solution than in nonpolar media, which indicates that the urate anions are the most active species. The free radical scavenging activity of the studied compounds was found to be excellent for (*)OH, and very good for (*)OCH(3). In addition, 1-methyluric acid is predicted to moderately protect against peroxyl oxidation, while the protective effects of uric acid against these particular species are not expected to be significant. In addition, 1-methyluric acid was found to be a better radical scavenger than its precursor, caffeine, suggesting that the antiradical activity of the latter might be explained by the action of its metabolites, rather than by its direct activity. PMID- 22097929 TI - Reconstruction of a beech population bottleneck using archival demographic information and Bayesian analysis of genetic data. AB - Range expansion and contraction has occurred in the history of most species and can seriously impact patterns of genetic diversity. Historical data about range change are rare and generally appropriate for studies at large scales, whereas the individual pollen and seed dispersal events that form the basis of geneflow and colonization generally occur at a local scale. In this study, we investigated range change in Fagus sylvatica on Mont Ventoux, France, using historical data from 1838 to the present and approximate Bayesian computation (ABC) analyses of genetic data. From the historical data, we identified a population minimum in 1845 and located remnant populations at least 200 years old. The ABC analysis selected a demographic scenario with three populations, corresponding to two remnant populations and one area of recent expansion. It also identified expansion from a smaller ancestral population but did not find that this expansion followed a population bottleneck, as suggested by the historical data. Despite a strong support to the selected scenario for our data set, the ABC approach showed a low power to discriminate among scenarios on average and a low ability to accurately estimate effective population sizes and divergence dates, probably due to the temporal scale of the study. This study provides an unusual opportunity to test ABC analysis in a system with a well-documented demographic history and identify discrepancies between the results of historical, classical population genetic and ABC analyses. The results also provide valuable insights into genetic processes at work at a fine spatial and temporal scale in range change and colonization. PMID- 22097928 TI - Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers. AB - Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole-brain blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole-brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli. PMID- 22097930 TI - MRI features of hepatocellular carcinoma expressing progenitor cell markers. AB - BACKGROUND & AIMS: To determine whether magnetic resonance (MR) imaging features differ between hepatocellular carcinomas (HCCs) with and without expression of progenitor cell markers, such as cytokeratin (CK) 19 and epithelial cell adhesion molecule (EpCAM). METHODS: Sixty-three patients with 71 HCCs who underwent surgery after preoperative gadoxetic acid-enhanced MR imaging were evaluated. HCCs expressing progenitor cell markers were defined as showing CK19 or EpCAM expression. MR imaging features, including the fat component, arterial enhancement (global vs. peripheral), dynamic enhancement (washout vs. progressive or persistent), nodule-in-nodule appearance and MR gross morphology (expanding vs. non-expanding), were compared between HCCs with and without progenitor cell markers expression. Lesion-to-liver signal intensity ratio (SIR) and apparent diffusion coefficient values were compared using an independent samples t-test. Early recurrence rates were also compared. RESULTS: HCCs expressing progenitor cell markers were more commonly of the non-expanding type (P = 0.016), more frequently had a progressive or persistent dynamic enhancement pattern (P = 0.008) and less frequently demonstrated a nodule-in-nodule appearance (P = 0.009). HCCs expressing progenitor cell markers had significantly higher SIRs on diffusion-weighted images (DWIs) (b = 50 and 800, P < 0.001; b = 400, P = 0.001) and a significantly lower SIR on hepatobiliary phase images (P = 0.024). The early recurrence rate was significantly higher in patients with prior HCCs that expressed progenitor cell markers (P = 0.045). CONCLUSIONS: HCCs expressing progenitor cell markers can be characterized according to their non-expanding MR gross morphology, persistent or progressive dynamic enhancement patterns, higher SIRs on DWIs, lower SIRs on hepatobiliary phase images and less frequent nodule in-nodule appearance. PMID- 22097931 TI - Characterization of microRNA expression profiles associated with hepatitis B virus replication and clearance in vivo and in vitro. AB - BACKGROUND AND AIM: Alpha interferon (IFN-alpha) is an approved treatment for chronic hepatitis B (CHB). MicroRNA (miRNA) are currently known as a part of IFN mediated antiviral defense. We aimed at characterizing the miRNA expression associated with hepatitis B virus (HBV) replication and IFN-mediated HBV clearance. METHODS: We investigated the expression patterns of cellular miRNA induced by HBV replication and/or IFN-alpha treatment in HepG2 cells, and also analyzed the miRNA response in peripheral blood mononuclear cells in CHB patients on IFN-alpha treatment. The differentially expressed miRNA were verified using quantitative real-time polymerase chain reaction and an miRNA expression pattern was classified based on the final virological response. RESULTS: A total of 223 miRNA were differentially expressed (> 1.5 folds) between the HepG2.2.15 and HepG2 cells, including 24 highly differentially expressed miRNA (> 5 folds). With 12 h of IFN-alpha treatment, 23 totally differentially expressed miRNA were identified in HepG2 cells; whereas only five miRNA were identified in HepG2.2.15 cells. Similar amounts of the miRNA were regulated in patients with HBeAg or non HBeAg seroconversion; whereas levels of eight miRNA were significantly differentially expressed between the two groups. CONCLUSIONS: HBV replication alters miRNA expression profiles and impairs IFN-inducible miRNA response in HepG2 cells. The miRNA expression pattern of peripheral blood mononuclear cells in CHB patients with IFN therapy can be associated with their therapeutic outcome. PMID- 22097932 TI - Narrowband ultraviolet B phototherapy decreased the serum IL-17E level in a patient with psoriasis vulgaris. PMID- 22097933 TI - Predictors of persistence in girls with attention deficit hyperactivity disorder: results from an 11-year controlled follow-up study. AB - OBJECTIVE: This study sought to examine the age-dependent persistence of attention deficit hyperactivity disorder (ADHD) and its predictors in a large sample of girls with and without ADHD followed prospectively for 11 years into young adulthood. METHOD: Participants were girls with (N=96) and without (N=91) ADHD and were 6-17 years old at the baseline assessment (mean age, 11 years) and 15-30 years old at the follow-up assessment (mean: 22 years). Participants were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning. RESULTS: At the 11-year follow-up, 33.3% met full criteria for ADHD, 29.2% showed partial persistence of the disorder, 10.4% had impaired functioning, and 4.2% were remitted but treated (77.1% of the sample). Predictors of persistence were psychiatric comorbidity, family history of psychopathology, and family and school functioning at baseline. CONCLUSION: These long-term, prospective, follow-up findings extend to girls findings that ADHD is persistent over the long term and can be predicted from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier. PMID- 22097934 TI - Towards an evidence-based process for the clinical interpretation of copy number variation. AB - The evidence-based review (EBR) process has been widely used to develop standards for medical decision-making and to explore complex clinical questions. This approach can be applied to genetic tests, such as chromosomal microarrays, in order to assist in the clinical interpretation of certain copy number variants (CNVs), particularly those that are rare, and guide array design for optimal clinical utility. To address these issues, the International Standards for Cytogenomic Arrays Consortium has established an EBR Work Group charged with building a framework to systematically assess the potential clinical relevance of CNVs throughout the genome. This group has developed a rating system enumerating the evidence supporting or refuting dosage sensitivity for individual genes and regions that considers the following criteria: number of causative mutations reported; patterns of inheritance; consistency of phenotype; evidence from large scale case-control studies; mutational mechanisms; data from public genome variation databases; and expert consensus opinion. The system is designed to be dynamic in nature, with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected will be displayed within a publically available database, and can be used in part to inform clinical laboratory CNV interpretations as well as to guide array design. PMID- 22097935 TI - Bone mass of the mandible and the risk of breast cancer among Japanese postmenopausal women. PMID- 22097936 TI - Microsatellite instability: detection and management in sporadic colorectal cancer. PMID- 22097937 TI - Can tertiary prevention of hepatocellular carcinoma be achieved by nucleos(t)ide analogs therapy of hepatitis B? PMID- 22097938 TI - Literature review in cases with exacerbation of ulcerative colitis induced by treatment with interferon and/or ribavirin. AB - Ulcerative colitis (UC) is an immune disorder of the gastrointestinal tract which has been reported to be precipitated by interferon (IFN) therapy. We describe the results of a literature review of cases in which the development or exacerbation of UC was coincident with IFN and/or ribavirin (RIB) treatment for chronic hepatitis C. We summarized the studies on the effectiveness of IFN for UC or Crohn's disease, which were primarily carried out in Europe and the USA. In the nine reported cases of UC exacerbation by IFN therapy in Japan, seven involved IFN-alpha, one involved IFN-alpha2b plus RIB, and the other involved IFN-beta; thus cases induced by IFN-alpha were more common. The period between the initiation of IFN treatment and the development or exacerbation of UC varied widely among the reported cases (from 1 day to 4.5 years). The reports have all assumed a cause-and-effect correlation between IFN treatment and UC. However, although combination therapy of IFN and RIB has become widespread in Japan, UC development or exacerbation induced by IFN has not increased concurrently. Conversely, numerous studies reporting the effectiveness of IFN for treating UC and Crohn's disease have been published in Europe and the USA. One reason for this finding may be the difference in the balance of T helper cell 1 and T helper cell 2 between populations. PMID- 22097939 TI - Hepatitis C recurrence after liver transplantation: has the human leukocyte antigen mismatching at individual loci a role? AB - BACKGROUND AND AIM: The objective of this 11-year cohort retrospective study conducted in adult patients with chronic hepatitis C virus (HCV) who underwent liver transplantation (LT) was to identify whether human leukocyte antigen (HLA) mismatching is associated with the recurrence of HCV and with the time to recurrence of HCV. METHODS: Among the 181 patients (74% men; mean age: 54 years, range 25-71) who underwent a LT between 1995 and 2006 in the study center, 163 had relevant data in their medical chart documenting HCV recurrence, and 107 (65.64%) reported a histological evidence of HCV recurrence. RESULTS: Survival was 78% at 5 years. There was no significant relationship between the total score of HLA-mismatches and the recurrence of HCV. Similarly, there was no significant relationship between the total score of HLA mismatches and the time to recurrence of HCV. For the analyses at each individual locus, a significant relationship between the individual scores of HLA-mismatches and the recurrence of HCV were observed. Out of the 40 patients who experienced a rejection, the rate of recurrence was not different according to the severity of the rejection (75% mild, 64% moderate and 64% for severe rejection). CONCLUSIONS: In conclusion, this large study did not demonstrate any relationship between the total score of HLA mismatches and HCV-recurrence. Contrarily a significant relationship between the individual scores of HLA mismatches (HLA-A3, HLA-B35, HLA-DR3, HLA-DR7, HLA DQ2, HLA-DQ2-0) and the recurrence of HCV were observed. PMID- 22097940 TI - Education and imaging. Gastrointestinal: asymptomatic spontaneous isolated dissection of superior mesenteric artery diagnosed incidentally. PMID- 22097941 TI - Education and imaging. Gastrointestinal: a gastrointestinal stromal tumour (GIST) arising in a Meckel's diverticulum. PMID- 22097942 TI - Education and imaging. Hepatobiliary and pancreatic: Niemann-Pick disease. PMID- 22097945 TI - Bone formation analysis: effect of quantification procedures on the study outcome. AB - Quantification of the amount of newly formed bone is an essential part of bone regeneration studies. Histomorphometry, based on histological sections of plastic embedded specimens, is the most frequently applied technique in this assessment. Before performing image analysis, a specific region of interest (ROI) has to be determined. Based on the histological procedure, different areas within the ROI can be discriminated and assigned to relevant tissue structures. However, in literature not much attention is paid to the effect of the histological procedures on the final outcome of the histomorphometrical measurements on bone regeneration. In this study, the histomorphometrical bone formation of the intramedullary cavity of the guinea pig tibia, filled with calcium phosphate cement, was quantified in plastic-embedded and paraffin-embedded specimens and in specimens analyzed with scanning electron microscopy in the backscattering mode (SEM-BS). The data showed that the histological procedure significantly affected the measured bone amount. Therefore, it is recommended that scaffold characteristics are carefully considered in selecting a proper technique for the analysis of bone formation in bone tissue engineering studies. The results of this study identified high-resolution SEM-BS and elastic van Gieson staining of decalcified histological sections as recommendable techniques for evaluating bone formation. PMID- 22097946 TI - Improved ruthenium catalysts for Z-selective olefin metathesis. AB - Several new C-H-activated ruthenium catalysts for Z-selective olefin metathesis have been synthesized. Both the carboxylate ligand and the aryl group of the N heterocyclic carbene have been altered and the resulting catalysts evaluated using a range of metathesis reactions. Substitution of bidentate with monodentate X-type ligands led to a severe attenuation of metathesis activity and selectivity, while minor differences were observed between bidentate ligands within the same family (e.g., carboxylates). The use of nitrato-type ligands in place of carboxylates afforded a significant improvement in metathesis activity and selectivity. With these catalysts, turnover numbers approaching 1000 were possible for a variety of cross-metathesis reactions, including the synthesis of industrially relevant products. PMID- 22097952 TI - Genetic prion disease-associated myelodysplasia and SIADH in siblings. PMID- 22097953 TI - Termination of refractory focal status epilepticus by the P-glycoprotein inhibitor verapamil. PMID- 22097954 TI - De novo P102L mutation in a patient with Gerstmann-Straussler-Scheinker disease. PMID- 22097955 TI - Procedure of generating the individually matched bone scaffolds. AB - The pace of modern life forced continuous high readiness and proper condition of motion systems on human beings. The techniques used in medicine and orthopaedics enable treatment of even highly complicated injuries and pathological states. One of them involves the use of bone scaffolding - the technique being intensively developed, which seems to have a promising future. Based on a numerical modelling, it is possible to match that type of implant to the needs of individual patient, with consideration for both biomechanical factors (patient weight, bone size and its defects) and the applicable implantation techniques. Vast possibilities are offered by the application of the finite element method as a technique enabling verification of an implant with the individually matched geometry and material. The paper presents the procedure aimed at generating the bone scaffold structure that enables the stresses created in the contact places of implant with the surrounding bone tissue to be reduced. High stresses may lead to local damages to the tissue and, in extreme cases, to the destruction of a scaffold. The present procedure is based on the theory of genetic algorithms and, due to several models widely known in biomechanics, allows stresses in places of bone contact with implant to be significantly reduced. PMID- 22097956 TI - A cutaneous vascular neoplasm with hobnail microscopic morphology and unusual gross features. AB - Vascular tumors are categorized into benign hemangiomas, frankly malignant angiosarcomas and tumors with intermediate biological behavior (hemangioendotheliomas). The latter group includes hemangioendotheliomas of the epithelioid, kaposiform, retiform and composite subtypes. Furthermore, a heterogeneous group of both benign and intermediate vascular tumors exhibits a peculiar hobnail cell morphology. This heterogeneous group encompasses hobnail hemangioma, retiform hemangioendothelioma, papillary intralymphatic angioendothelioma and a subset of angiosarcoma. We herein present a case of a cutaneous vascular neoplasm with hobnail morphology and unusual gross features. PMID- 22097957 TI - Oral infection with Porphyromonas gingivalis and systemic cytokine profile in C57BL/6.KOR-ApoE shl mice. AB - BACKGROUND AND OBJECTIVE: Periodontal infection affects atherosclerotic diseases, such as coronary heart diseases. Mouse models have revealed that oral infection with Porphyromonas gingivalis induces changes in inflammatory- and lipid metabolism-related gene expression, regardless of the development of atherosclerotic lesions. However, the serum protein expression profile in the oral infection model has not been investigated. The present study aimed to analyse the effect of oral infection with P. gingivalis on the expression levels of multiple cytokines in the serum in apolipoprotein E-deficient mice by using a cytokine antibody array. MATERIAL AND METHODS: C57BL/6.KOR-Apoe(shl) mice were orally infected with P. gingivalis five times at 3 day intervals and were then killed. Splenocytes were isolated and analysed for proliferative activity and immunoglobulin G (IgG) production in response to in vitro restimulation with P. gingivalis. The expression levels of various cytokines in the sera were analysed using a mouse antibody array glass chip. RESULTS: Splenocytes from P. gingivalis infected mice demonstrated significantly greater proliferation and IgG production in response to P. gingivalis compared with those from sham-infected mice. Antibody array analysis revealed the selective upregulation of matrix metalloproteinase 3, intercellular adhesion molecule 1, insulin-like growth factor binding protein 2 and chemokine (C-X-C motif) ligand 7 and the downregulation of interleukin-17, tumor necrosis factor-alpha and L-selectin. CONCLUSION: These data demonstrate that oral infection with P. gingivalis induces alterations in systemic cytokine production. These cytokines could play roles in the development not only of periodontitis but also of atherosclerosis. PMID- 22097958 TI - Molecular dynamics simulation and free energy calculation studies of the binding mechanism of allosteric inhibitors with p38alpha MAP kinase. AB - p38 MAP kinase is a promising target for anti-inflammatory treatment. The classical kinase inhibitors imatinib and sorafenib as well as BI-1 and BIRB-796 were reported to bind in the DFG-out form of human p38alpha, known as type II or allosteric kinase inhibitors. Although DFG-out conformation has attracted great interest in the design of type II kinase inhibitors, the structural requirements for binding and mechanism of stabilization of DFG-out conformation remain unclear. As allosteric inhibition is important to the selectivity of kinase inhibitor, herein the binding modes of imatinib, sorafenib, BI-1 and BIRB-796 to p38alpha were investigated by molecular dynamics simulation. Binding free energies were calculated by molecular mechanics/Poisson-Boltzmann surface area method. The predicted binding affinities can give a good explanation of the activity difference of the studied inhibitors. Furthermore, binding free energies decomposition analysis and further structural analysis indicate that the dominating effect of van der Waals interaction drives the binding process, and key residues, such as Lys53, Gly71, Leu75, Ile84, Thr106, Met109, Leu167, Asp168, and Phe169, play important roles by forming hydrogen bond, salt bridge, and hydrophobic interactions with the DFG-out conformation of p38alpha. Finally, we also conducted a detailed analysis of BI-1, imatinib, and sorafenib binding to p38alpha in comparison with BIRB-796 exploited for gaining potency as well as selectivity of p38 inhibitors. These results are expected to be useful for future rational design of novel type II p38 inhibitors. PMID- 22097959 TI - New species of Arostrilepis (Eucestoda: Hymenolepididae) in members of Cricetidae and Geomyidae (Rodentia) from the western Nearctic. AB - Abstract : Specimens originally identified as Arostrilepis horrida from the Nearctic are revised, contributing to the recognition of a complex of cryptic species distributed across the Holarctic region. Previously unrecognized species are described based on specimens in cricetid (Neotominae) and geomyid rodents. Arostrilepis mariettavogeae n. sp. in Peromyscus californicus from Monterey County, California and Arostrilepis schilleri n. sp. in Thomomys bulbivorus from Corvallis, Oregon are characterized. Consistent with recent studies defining diversity in the genus, form, size, and spination (pattern, shape, and size) of the cirrus are diagnostic; species are further distinguished by the relative position and length of the cirrus sac and arrangement of the testes. Species of Arostrilepis have not previously been described in rodents outside of the Arvicolinae or from localities in the Nearctic. These studies emphasize the need for routine deposition of archival specimens and information, from survey, ecological, and biogeographic studies, in museum collections to serve as self correcting records for biodiversity at local, regional, and continental scales. PMID- 22097960 TI - Tryptophan 697 modulates hydride and interflavin electron transfer in human methionine synthase reductase. AB - Human methionine synthase reductase (MSR), a diflavin oxidoreductase, plays a vital role in methionine and folate metabolism by sustaining methionine synthase (MS) activity. MSR catalyzes the oxidation of NADPH and shuttles electrons via its FAD and FMN cofactors to inactive MS-cob(II)alamin. A conserved aromatic residue (Trp697) positioned next to the FAD isoalloxazine ring controls nicotinamide binding and catalysis in related flavoproteins. We created four MSR mutants (W697S, W697H, S698Delta, and S698A) and studied their associated kinetic behavior. Multiwavelength stopped-flow analysis reveals that NADPH reduction of the C-terminal Ser698 mutants occurs in three resolvable kinetic steps encompassing transfer of a hydride ion to FAD, semiquinone formation (indicating FAD to FMN electron transfer), and slow flavin reduction by a second molecule of NADPH. Corresponding experiments with the W697 mutants show a two-step flavin reduction without an observable semiquinone intermediate, indicating that W697 supports FAD to FMN electron transfer. Accelerated rates of FAD reduction, steady state cytochrome c(3+) turnover, and uncoupled NADPH oxidation in the S698Delta and W697H mutants may be attributed to a decrease in the energy barrier for displacement of W697 by NADPH. Binding of NADP(+), but not 2',5'-ADP, is tighter for all mutants than for native MSR. The combined studies demonstrate that while W697 attenuates hydride transfer, it ensures coenzyme selectivity and accelerates FAD to FMN electron transfer. Moreover, analysis of analogous cytochrome P450 reductase (CPR) variants points to key differences in the driving force for flavin reduction and suggests that the conserved FAD stacking tryptophan residue in CPR also promotes interflavin electron transfer. PMID- 22097961 TI - Capsaicin instillation for postoperative pain following total knee arthroplasty. PMID- 22097962 TI - Evaluation of risk factors and effect of physical activity in caesarean section in nulliparous women. AB - OBJECTIVE: The aim of this study was to evaluate risk factors for caesarean section (CS) in nulliparous women and to determine the effect of physical activity on ease of labour. METHODS: A prospective observational study, including 282 nulliparous women at 37-41 gestational weeks was conducted. Maternal demographic characteristics, obstetric history and Modified Grimby scale for evaluation of physical activity were noted. Patients were classified into spontaneous labour and induction group. Multiple logistic regression model was used to assess independent risk factors for type of delivery. RESULTS: Caesarean rate was increasing with higher educational status (p < 0.001). Maternal height, maternal and paternal age were higher, whereas dilatation on admission was lower in CS group (p < 0.05). Maternal age, weight gain and CS rate were higher in induction group (p < 0.05). Fetal distress as a cause of CS was detected higher in induction group (p < 0.05). Physical activity has no significant effect on mode of delivery (p > 0.05). Maternal height (p = 0.011), and cervical dilatation on admission (p = 0.004) were identified as predictor factors for CS. CONCLUSION: Cervical dilatation is the most important negative predictive factor for CS, whereas, moderate physical activity has no effect on mode of delivery. Fetal distress was the most frequent cause of CS in induction group. PMID- 22097963 TI - Tunnel frit: a nonmetallic in-capillary frit for nanoflow ultra high-performance liquid chromatography-mass spectrometryapplications. AB - In this study, an easy method to fabricate a durable in-capillary frit was developed for use in nanoflow liquid chromatography (nanoLC). A small orifice was tunneled into the sol-gel frit during the polymerization process resulting in the simple fabrication of a tunnel frit. A short packing tunnel frit column (2 cm, C(18) particles) was able to sustain over 10,000 psi continuous liquid flow for 10 days without observation of particle loss, and back pressure variation was less than 5%. The tunnel frit was successfully applied to the fabrication of nanoflow ultra high-performance liquid chromatography (nano-UHPLC) trap and analytical columns. In the analysis of tryptic peptides, the tunnel frit trap and analytical columns were demonstrated to have high separation efficiency and sensitivity. In analysis of phosphopeptides, the use of the nonmetallic tunnel frit column showed better sensitivity than the metallic frit column. This design can facilitate the preparation of nano-HPLC and nano-UHPLC columns and the packing material can easily be refilled when the column is severely contaminated or clogged. PMID- 22097966 TI - Multiple lines of evidence for demographic and range expansion of a temperate species (Hyla sarda) during the last glaciation. AB - Many temperate species experienced demographic and range contractions in response to climatic changes during Pleistocene glaciations. In this study, we investigate the evolutionary history of the Tyrrhenian tree frog Hyla sarda, a species inhabiting the Corsica-Sardinia island system (Western Mediterranean basin). We used sequence analysis of two mitochondrial (overall 1229 bp) and three nuclear (overall 1692 bp) gene fragments to assess the phylogeography and demographic history of this species, and species distribution modelling (SDM) to predict its range variation over time. Phylogeographic, historical demographic and SDM analyses consistently indicate that H. sarda does not conform to the scenario generally expected for temperate species but rather underwent demographic and range expansion mostly during the last glacial phase. Palaeogeographic data and SDM analyses suggest that such expansion was driven by the glaciation-induced increase in lowland areas during marine regression. This unusual scenario suggests that at least some temperate species may not have suffered the adverse effects of glacial climate on their population size and range extent, owing to the mitigating effects of other glaciations-induced palaeoenvironmental changes. We discuss previous clues for the occurrence of such a scenario in other species and some possible challenges with its identification. Early phylogeographic literature suggested that responses to the Pleistocene glacial-interglacial cycles were expected to vary among species and regions. Our results point out that such variation may have been greater than previously thought. PMID- 22097967 TI - Role of stress-induced NKG2D ligands in liver diseases. AB - Cell death by apoptosis is a prominent feature in a variety of liver diseases. It is likely that apoptosis is the initial cellular response to hepatocyte and biliary injury, which then leads to the initiation of cellular and cytokine cascades culminating in hepatocyte death with subsequent fibrosis and cirrhosis. This sequence of events is of paramount clinical importance. Recently, soluble forms of the major histocompatibility complex class I-related chains A and closely related B (MIC A and B) were reported to be increased in patients with a variety of liver diseases. MIC A and B are cell surface glycoproteins that function as indicators for cellular stress and thus activate circulating cytotoxic natural killer (NK) cells. The interaction between MIC A and B with their cognate receptor natural killer group 2 member D (NKG2D) culminates in enhanced liver cell death, which is mediated in part by apoptotic mechanisms. The present overview focuses on the role of the stress-induced NKG2D ligands MIC A and B in diverse liver diseases. Critical insights into these complex relations may help to promote rationally based therapies in liver diseases. Importantly, we hope that this overview will help to stimulate further studies into mechanisms by which stress ligands mediate cell death and its sequale. PMID- 22097968 TI - Structural and dynamical insights into the molten-globule form of ovalbumin. AB - Ovalbumin is a 45 kDa egg-white glycoprotein which belongs to the class of serpin superfamily. We have studied the structural properties of both native and partially unfolded molten-globule forms of ovalbumin using a diverse array of spectroscopic tools. Time-resolved fluorescence measurements provided important structural and dynamical insights into the native and molten-globule states. Fluorescence anisotropy decay analysis indicated that there is a conformational swelling from the native to the molten-globule form of ovalbumin. We have also carried out red-edge excitation shift measurements to probe the dipolar relaxation dynamics around the intrinsic tryptophan residues. Additionally, stopped-flow fluorescence experiments revealed that the conformational transition from the native to the molten-globule form proceeds in a stepwise manner involving a burst-phase with a submillisecond conformational change followed by biphasic slower conformational reorganizations on the millisecond time scale leading to the final molten-globule state. PMID- 22097965 TI - Toxicological considerations when creating nanoparticle-based drugs and drug delivery systems. AB - INTRODUCTION: The biggest challenge faced by the scientific community involved in drug development is to deliver safe and effective dosage of drugs without causing systemic toxicity. Therefore, novel nano-based delivery vehicles specifically targeting tumors but not normal tissues are urgently needed. AREAS COVERED: Nanoparticles have beneficial aspects but can be toxic themselves, which is always a concern for any drug or delivery agent. This review examines and details the toxicological aspects that should be considered when planning to use nanoparticles in animals or in man for drug delivery or imaging. Subjects discussed in this review include i) overviews of applications of various nanoparticles for drug delivery and imaging; ii) toxicological aspects to consider when selecting particular nanoparticles for use in various applications in animals or man; iii) hurdles faced when examining nanoparticle toxicity; and iv) current approaches for assessing nanoparticle toxicity. EXPERT OPINION: Nanotechnology has significant potential for advancing therapeutic efficacy and imaging in cancer; however, these agents can be toxic. Therefore, toxicity needs to be considered when selecting nanoparticles for a particular application. Methods for assessing nanoparticle toxicity need to be improved and standardized across all nanotechnology platforms in order to speed up the application of nanoparticle use in humans. PMID- 22097969 TI - Cyclooxygenase-2 and Akt mediate multiple growth-factor-induced epithelial mesenchymal transition in human hepatocellular carcinoma. AB - BACKGROUND AND AIM: Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma (HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies. METHODS: The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor beta-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined. RESULTS: LH86 cells display epithelial morphology. Transforming-growth-factor-beta-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth factor-induced mesenchymal changes in them were associated with loss of E cadherin, albumin, alpha-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin E2 (PGE2), Akt and phosphorylated Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT. CONCLUSIONS: Multiple growth factors induce EMT in HCC. COX-2 and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC. PMID- 22097970 TI - Patent blue dye and an atypical anaphylactic reaction after sentinel lymph node biopsy in early breast cancer. PMID- 22097971 TI - The use of tumescent local anaesthesia in ablative laser treatments. PMID- 22097975 TI - Outcomes of the Seventh International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion and Second Annual Meeting of the International Society for Pediatric Mechanical Cardiopulmonary Support. PMID- 22097972 TI - Five years of treatment with adefovir dipivoxil in Chinese patients with HBeAg positive chronic hepatitis B. AB - BACKGROUND: Adefovir dipivoxil (ADV) is a nucleotide analogue with proven efficacy in chronic hepatitis B (CHB). AIMS: This study investigated long-term ADV treatment in HBeAg-positive patients. METHODS: A total of 480 Chinese subjects with HBeAg-positive CHB who participated in a 1-year, double-blind, placebo-controlled study of ADV 10 mg daily were offered open-label continuation for a further 208 weeks. RESULTS: A total of 390 subjects completed 5 years of treatment. Baseline median hepatitis B virus (HBV) DNA was 8.8 log(10) copies/ml and alanine aminotransferase (ALT) 2.6 * upper limit of normal. Treatment with ADV resulted in sustained suppression of median HBV DNA by 4.8, 5.0, 5.1, 5.4 and 5.5 log(10) copies/ml after 1, 2, 3, 4 and 5 years respectively. Continuous treatment with ADV led to a progressive increase in the proportion of subjects achieving undetectable HBV DNA, from 28% after 1 year to 58% after 5 years. HBeAg seroconversion rates increased cumulatively from 11% after 1 year to 29% after 5 years. HBsAg seroconversion was achieved by 1.0% of patients. ADV resulted in ALT normalization that was maintained throughout this study in 75-79% of subjects. Virological breakthrough associated with ADV resistant mutations (rtN236T and rtA181V) occurred in 14.6% of subjects. ADV was well tolerated. CONCLUSION: Five years of ADV treatment in Chinese subjects with HBeAg-positive CHB resulted in increasing virological and serological responses and sustained biochemical responses over time. Virological resistance was identified in 14.6% of patients. Urgent switch or add-on therapy with a nucleoside analogue is necessary if ADV resistant mutations are detected, particularly rtN236T. Treatment was well tolerated. PMID- 22097976 TI - Istanbul Symposiums on Pediatric Extracorporeal Life Support Systems. PMID- 22097977 TI - The impact of extracorporeal membrane oxygenation on survival in pediatric patients with respiratory and heart failure: review of our experience. AB - Extracorporeal membrane oxygenation (ECMO) is widely used for circulatory support in pediatric cardiac patients with low cardiac output and hypoxemia. We retrospectively evaluated the efficacy of ECMO support for respiratory and heart failure in infants and children. From April 2002 to February 2011, 14 patients aged 19 days to 20 years old (average 44 months), with body weight 2.6 kg to 71 kg (median 14.1 kg), underwent ECMO support for failing cardiac function, hypoxemia, and low cardiac output syndrome. In 12 patients, ECMO was introduced after operation for congenital heart disease (four with complete repair including Fontan circulation, and eight with palliative repair). In one patient, ECMO was introduced after partial pulmonary resection for congenital cystic adenomatoid malformation because of respiratory failure. ECMO was introduced in a patient with severe heart failure caused by fulminant myocarditis. Patients' demographics, duration of extracorporeal membrane oxygenation, additional support, and outcomes were analyzed. Ten patients (71%) were successfully weaned from ECMO, and eight patients (57%) were discharged from the hospital. The mean duration of ECMO support was 332 h (range 11-2030 h). Although management of the ECMO circuit, including anticoagulation (activated clotting time: 150-250), was conducted following the institutional practice guidelines, it was difficult to control the bleeding. Seven patients required renal replacement therapy during ECMO support using peritoneal dialysis or continuous hemodiafiltration. Five patients had additional operative procedures: systemic-pulmonary shunt in two, bidirectional Glenn takedown with right modified Blalock-Taussig shunt, total cavopulmonary connection takedown, and redo ECMO in one patient each. The patient who had the longest ECMO support for respiratory failure due to acute respiratory distress syndrome after lung surgery was successfully weaned from ECMO because high-frequency oscillation (HFO) improved respiratory function. ECMO for heart and respiratory failure in infants and children is effective and allows time for recovery of cardiac dysfunction and acute hypoxic insult. The long-term ECMO support for over 2000 h was very rare, but it was possible to wean this patient from ECMO using HFO. PMID- 22097978 TI - Comparison of parameters for detection of splanchnic hypoxia in children undergoing cardiopulmonary bypass with pulsatile versus nonpulsatile normothermia or hypothermia during congenital heart surgeries. AB - The aim of this study is to evaluate gastric mucosal oxygenation together with whole-body oxygen changes in infants undergoing congenital heart surgery with cardiopulmonary bypass (CPB) procedure and the use of either pulsatile or nonpulsatile mode of perfusion with normothermia and pulsatile or nonpulsatile moderate hypothermia. Sixty infants undergoing congenital cardiac surgery were randomized into four groups as: nonpulsatile normothermia CPB (NNCPB, n = 15), pulsatile normothermia CPB (PNCPB, n = 15), nonpulsatile moderate hypothermia CPB (NHCPB, n = 15), and pulsatile moderate hypothermia CPB (PHCPB, n = 15) groups. In NNCPB and PNCPB groups, mild hypothermia was used (35 degrees C), whereas in NHCPB and PHCPB groups, moderate hypothermia (28 degrees C) was used. Gastric intramucosal pH (pHi), whole-body oxygen delivery (DO(2)) and consumption (VO(2)), and whole-body oxygen extraction fraction were measured at sequential time points intraoperatively and up to 2 h postoperatively. The measurement of continuous tonometry data was collected at desired intervals. The values of DO(2), VO(2), and whole-body oxygen extraction fraction were not different between groups before CPB and during CPB, whereas the PNCPB group showed higher values of DO(2), VO(2), and whole-body oxygen extraction fraction compared to the other groups at the measurement levels of 20 and 60 min after aortic cross clamp, end of CPB, and 2 h after CPB (P < 0.0001). Between groups, no difference was observed for pHi, lactate, and cardiac index values (P > 0.05). This study shows that the use of normothermic pulsatile perfusion (35 degrees C) provides better gastric mucosal oxygenation as compared to other perfusion strategies in neonates and infants undergoing congenital heart surgery with CPB procedures. PMID- 22097979 TI - A method for anticoagulation of children on mechanical circulatory support. AB - Anticoagulation of children on mechanical circulatory support presents a challenge. We implanted 28 devices in children and infants using a consistent anticoagulation protocol. We performed a retrospective review of all children implanted in our program with mechanical assist devices since 1997. Heparin, dipyridamole, and aspirin were used for anticoagulation and antiaggregation. Coagulation monitoring included thromboelastography (TEG), platelet aggregration studies, international normalized ratio, partial thromboplastin time, and platelet count. Twenty-eight children, ages 1 month to 16 years (mean 5.3; median 2.4 years), were implanted for 3-107 days (mean 27; median 17). Eighteen received left ventricular assist devices, seven received biventricular assist devices, and three received total artificial hearts. Adverse events during the 720 days of device support included the following: six (21%) reoperations for bleeding; seven strokes (25%): two fatal, two with a mild residual deficit, and three without deficit; and three (11%) visceral emboli: two fatal and one nonfatal. There were eight deaths (29%). Causes of death were embolic (four), graft failure post transplantation (one), preimplant anoxic brain damage (two), and postexplant heart failure (one). 24/28 (86%) survived to transplantation or weaning from device and 20/28 (71%) were discharged from the hospital, 10 after transplantation and 10 after native heart recovery. All 20 early survivors survived long term. We describe an anticoagulation protocol based upon TEG and platelet aggregation studies and using heparin, aspirin, and dipyridamole. Adequate anticoagulation is more difficult in children. However, 71% of the patients in our study survived long term. PMID- 22097980 TI - Antithrombin replacement during extracorporeal membrane oxygenation. AB - Heparin remains the predominant anticoagulant during extracorporeal membrane oxygenation (ECMO). Heparin acts by potentiating the anticoagulant effect of antithrombin (ATIII). Acquired ATIII deficiency, common in pediatric patients requiring ECMO, may result in ineffective anticoagulation with heparin. ATIII replacement may result in increased bleeding. Our objective is to determine ATIII's effect on anticoagulation and blood loss during ECMO. A retrospective chart review was performed of all patients at Children's Hospital of Wisconsin who received ATIII while supported on ECMO in 2009. ATIII activity levels, heparin drip rate, and activated clotting times (ACT) were compared before, 4, 8, and 24 h after ATIII administration. Chest tube output and packed red blood cell (pRBC) transfusion volume were compared from 24 h before ATIII administration to 24 h after. Twenty-eight patients received ATIII as a bolus dose during the course of 31 separate times on ECMO support. The median age of these patients was 0.3 years (range 1 day-19.5 years). ATIII activity increased significantly at 8 and 24 h after administration. No significant difference was noted in heparin drip rate, ACT levels, chest tube output, or pRBC transfusion volume. ATIII administration resulted in higher ATIII activity levels for 24 h without a significant effect on heparin dose, ACT, or measures of bleeding. PMID- 22097981 TI - Influence of mild metabolic acidosis on cardiac contractility and isoprenaline response in isolated ovine myocardium. AB - The postoperative course after major surgical procedures such as cardiothoracic operations is often accompanied by acute metabolic abnormalities due to large volume and temperature shifts. In general, those intervention-induced trauma might cause the use of catecholamines to stabilize hemodynamics. Within the cardiac community, there are still controversial discussions about standardized medical therapy to treat postoperative acidosis, for example, buffering versus nonbuffering for improving catecholaminergic response of myocardial contractility. The aim of this study was to investigate the influence of mild (and thus clinically relevant) acidosis on myocardial contractility and catecholamine response in explanted trabeculae of ovine hearts. Intact trabeculae (n = 24) were isolated from the right ventricle of healthy sheep hearts. Two different groups (group 1: pH = 7.40, n = 9 and group 2: pH = 7.20, n = 13) were investigated, and force amplitudes were measured at frequencies between 30 and 180 beats per minute and increasing catecholamine concentrations (isoprenaline 0 3 * 10(-6) mM). Force-frequency relation experiments in the presence of a physiological and/or mild acidotic pH solution showed no significant differences. Mean force amplitudes normalized to the lowest frequency showing no significant differences in force development between 0.5 and 3 Hz (n = 9 vs. 13, P = n.s.) (0.5 Hz absolute values 3.1 +/- 2.6 for pH = 7.40 vs. 3.8 +/- 2.6 mN/mm(2) for pH = 7.20, P = n.s.). Moreover, there was no significant difference in relaxation kinetics between the two groups. Furthermore, the experiments showed similar catecholamine responses in both groups. Force amplitudes normalized to baseline and maximum force showed no significant differences in force development between baseline and maximum isoprenaline concentrations (n = 6 vs. 9, P = n.s.) (baseline absolute values 4.3 +/- 4.0 for pH = 7.40 vs. 3.9 +/- 1.2 mN/mm(2) for pH = 7.20, P = n.s.). Additionally, relaxation kinetics did not show differences after catecholamine stimulation. The presented experiments revealed no significant negative inotropic effects on isometrically contracting ovine trabeculae with mild metabolic acidosis (pH = 7.2) compared with physiological pH (7.4). Additionally, similar catecholamine responses were seen in both groups. Further investigations (e.g., in vivo and/or in failing hearts with reduced compensatory reserves) will be necessary to examine optimal medical treatment for metabolic abnormalities after cardiac surgery. PMID- 22097982 TI - Cardioplegia and angiotensin II receptor antagonists modulate signal transducers and activators of transcription activation in neonatal rat myocytes. AB - Previous investigations have shown that the signal transducers and activators of transcription (STATs) signaling pathway play an important role in the modulation of apoptosis after ischemia and reperfusion. The mechanism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role. To investigate this hypothesis, we examined the effects of angiotension II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the downstream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohypertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4 degrees C) for 20 min in the Langendorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 cardioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antagonist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 8 12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfusion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a significant reduction in STAT2 and STAT5 tyrosine phosphorylation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supplemented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1beta (-57% in Group 2 vs. Group 1, P < 0.05). There were no significant differences in STAT3 phosphorylation among all groups. Only the addition of AT1 receptor antagonist to MSTH2 cardioplegia significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by tyrosine phosphorylation of STAT3. AT1 receptor antagonist added to cardioplegia represents an additional modality for enhancing myocardial protection during cardiac surgery and could contribute to optimize the ischemia tolerance of the pediatric heart. PMID- 22097983 TI - Development of magnetic bearing system for a new third-generation blood pump. AB - A magnetic bearing system is a crucial component in a third-generation blood pump, particularly when we consider aspects such as system durability and blood compatibility. Many factors such as efficiency, occupying volume, hemodynamic stability in the flow path, mechanical stability, and stiffness need to be considered for the use of a magnetic bearing system in a third-generation blood pump, and a number of studies have been conducted to develop novel magnetic bearing design for better handling of these factors. In this study, we developed and evaluated a new magnetic bearing system having a motor for a new third generation blood pump. This magnetic bearing system consists of a magnetic levitation compartment and a brushless direct current (BLDC) motor compartment. The active-control degree of freedom is one; this control is used for controlling the levitation in the axial direction. The levitation in the radial direction has a passive magnetic levitation structure. In order to improve the system efficiency, we separated the magnetic circuit for axial levitation by using a magnetic circuit for motor drive. Each magnetic circuit in the bearing system was designed to have a minimum gap by placing mechanical parts, such as the impeller blades, outside the circuit. A custom-designed noncontact gap sensor was used for minimizing the system volume. We fabricated an experimental prototype of the proposed magnetic bearing system and evaluated its performance by a control system using the Matlab xPC Target system. The noncontact gap sensor was an eddy current gap sensor with an outer diameter of 2.38 mm, thickness of 0.88 mm, and resolution of 5 um. The BLDC motor compartment was designed to have an outer diameter of 20 mm, length of 28.75 mm, and power of 4.5 W. It exhibited a torque of 8.6 mNm at 5000 rpm. The entire bearing system, including the motor and the sensor, had an outer diameter of 22 mm and a length of 97 mm. The prototype exhibited sufficient levitation performance in the stop state and the rotation state with a gap of 0.2 mm between the rotor and the stator. The system had a steady position error of 0.01 um in the stop state and a position error of 0.02 um at a rotational speed of 5000 rpm; the current consumption rates were 0.15 A and 0.17 A in the stop state and the rotation state, respectively. In summary, we developed and evaluated a unique magnetic bearing system with an integrated motor. We believe that our design will be an important basis for the further development of the design of an entire third-generation blood pump system. PMID- 22097984 TI - Incidence of healthcare-associated infections in a pediatric population with an extracorporeal ventricular assist device. AB - During the last decade, ventricular assist devices (VADs) have become a precious tool to support children with end-stage heart failure. However, thromboembolic events, bleeding, and infections may have a considerable impact on outcome. We retrospectively analyzed the incidence of healthcare-associated infections (HAIs) in nine patients supported by EXCOR Pediatric (Berlin Heart [BH]) VAD in a pediatric cardiosurgical intensive care unit between January 1, 2009 and March 31, 2011 (27 months). Median age was 8 months (interquartile range [IQR] 6-11), median weight 7.5 kg (IQR 4.5-8.5). Seven patients were supported with a left VAD, two with a biventricular VAD (BiVAD). Six patients with a left VAD underwent heart transplant after 89 days (median, IQR 41-143) of support. One patient is still on the waiting list. All patients with BiVAD died after 12 days of assistance due to VAD malfunction. Sixteen HAIs were reported in five out of nine patients (56%). All infected patients were supported by a left VAD. When compared with noninfected patients, they had a longer mechanical support period (median 131 days, IQR 75-164, vs. 25 days, IQR 11-61, P = 0.03), a longer intensive care unit stay (median 159 days, IQR 85-188, vs. 48 days, IQR 17-87, P = 0.06) and a longer length of hospital stay (median 186 days, IQR 105-222, vs. 64 days, IQR 34 113, P = 0.06). Overall, nine mechanical devices were replaced for thromboembolic issues, most of them (67%) in patients with VAD-related infections. Overall, infection rate was 17.6 per 1000 patients days, 1.3 BH endocarditis per 1000 BH days, 4.0 surgical sites infections per 1000 BH days, 12.5 central line associated blood stream infections per 1000 central venous catheter days, 5 catheter-associated urinary tract infections per 1000 urinary catheter days, and 13.5 ventilator-associated pneumonia cases per 1000 mechanical ventilation days. Overall, VAD-related infections were 5.4 per 1000 BH days. Of the 17 isolated pathogens, 53% were Gram-negative rods, with a prevalence of Pseudomonas aeruginosa (35.3%). Four bacteria were multidrug resistant (25%), three were carbapenem-resistant P. aeruginosa (50% of all isolated pseudomonads), and one was a methicillin-resistant S. aureus. VADs used as a bridge to cardiac transplantation are associated with a large number of HAIs. Patients with infected VADs were admitted for longer time in intensive care and in hospital with increased healthcare costs but with no impact on survival. PMID- 22097985 TI - Sodium alginate hydrogel-based bioprinting using a novel multinozzle bioprinting system. AB - Bioprinting is a technology for constructing bioartificial tissue or organs of complex three-dimensional (3-D) structure with high-precision spatial shape forming ability in larger scale than conventional tissue engineering methods and simultaneous multiple components composition ability. It utilizes computer controlled 3-D printer mechanism or solid free-form fabrication technologies. In this study, sodium alginate hydrogel that can be utilized for large-dimension tissue fabrication with its fast gelation property was studied regarding material specific printing technique and printing parameters using a multinozzle bioprinting system developed by the authors. A sodium alginate solution was prepared with a concentration of 1% (wt/vol), and 1% CaCl(2) solution was used as cross-linker for the gelation. The two materials were loaded in each of two nozzles in the multinozzle bioprinting system that has a total of four nozzles of which the injection speed can be independently controlled. A 3-D alginate structure was fabricated through layer-by-layer printing. Each layer was formed through two phases of printing, the first phase with the sodium alginate solution and the second phase with the calcium chloride solution, in identical printing pattern and speed condition. The target patterns were lattice shaped with 2-mm spacing and two different line widths. The nozzle moving speed was 6.67 mm/s, and the injection head speed was 10 um/s. For the two different line widths, two injection needles with inner diameters of 260 and 410 um were used. The number of layers accumulated was five in this experiment. By varying the nozzle moving speed and the injection speed, various pattern widths could be achieved. The feasibility of sodium alginate hydrogel free-form formation by alternate printing of alginate solution and sodium chloride solution was confirmed in the developed multinozzle bioprinting system. PMID- 22097987 TI - Systemic contact dermatitis. AB - Systemic contact dermatitis is an inflammatory skin disease that may occur in persons with contact allergy when they are exposed to the hapten orally, transcutaneously, per rectum, intravesically, intravenously, or by inhalation. The most common causes of systemic contact dermatitis are drugs used both topically and systemically. Other causes are ubiquitously occurring haptens, such as the metals nickel, cobalt, gold, and chromate, and aromatic substances such as spices. Avoidance of the offending hapten is the most obvious treatment. For some haptens, such as nickel, diet treatment may be effective. Chelation therapy with disulfiram is another therapeutic option in nickel-allergic patients with systemic contact dermatitis. Hyposensitization therapy has been attempted with some success in systemic contact dermatitis caused by nickel and Parthenium hysterophorus. PMID- 22097988 TI - Central centrifugal cicatricial alopecia - an approach to diagnosis and management. AB - Central centrifugal cicatricial alopecia (CCCA) occurs primarily in African American women and is the most common cause of scarring hair loss in this population. Since the mid 20th century, hair care practices of African-American women have been associated with CCCA, although there is developing evidence that the etiology of CCCA may be multifactorial. Clinically diagnosing CCCA may be challenging because it can resemble female pattern hair loss, alopecia areata, lichen planopilaris, or telogen effluvium. Therapeutic options are limited, thus the goal of treatment is to prevent progression of disease because once scar formation occurs, it is irreversible. PMID- 22097989 TI - Hypopigmented papules on the upper trunk and forearm of a young man. PMID- 22097990 TI - A nodule developing within a congenital verrucous-surfaced plaque on the lower back. PMID- 22097991 TI - Immunohistochemical profile of cytokeratins in pseudoepitheliomatous hyperplasia of cutaneous leishmaniasis. AB - BACKGROUND: The purpose of this study was to evaluate the immunohistochemical profile of cytokeratins (Ck) in pseudoepitheliomatous hyperplasia of cutaneous leishmaniasis (CL). METHODS: The tissue samples, with pseudoepitheliomatous hyperplasia, were collected from 37 patients (age 6-85 years old) with indolent ulcers in skin confirmed as CL. The lesions were submitted to immunolabeling for Ck pairs 4-13, 5-14, and 6-16. RESULTS: In the 37 CL cases, Ck4 and Ck13 staining were, in the majority of cases, negative. Of them, 33 and 35 cases were negative for Ck4 and Ck13, respectively. The Ck4 immunostaining was found in basal and parabasal layers, and Ck13 was viewed in the basal compartment of epithelium. Ck5 was found in 29 cases distributed homogeneously in all layers. Ck14 and Ck6 were found in all samples in all layers, and Ck16 was positive for all cases but heterogeneously found in the basal layer. CONCLUSION: In summary, we noticed that the pattern of some Ck staining in pseudoepitheliomatous hyperplasia in CL lesions revealed intense epithelial reinforcement, protection, and proliferation. PMID- 22097992 TI - Radiotherapy-induced pemphigus vulgaris with autoantibodies targeting a 110 kDa epidermal antigen. AB - BACKGROUND: Pemphigus is an autoimmune intraepidermal blistering disease mediated by autoantibodies targeting desmosomes. It can be induced by many triggers, such as ionizing radiation. METHODS: We report a case of radiotherapy-induced pemphigus (RIP) with a review of the published cases in the English and French literature. RESULTS: A 61-year old man was diagnosed to have epidermoid carcinoma of the piriform sinus and then received a 70 Gy radiation therapy. One month after the treatment completion, multiple blisters and erosions occurred initially on the site of irradiation, then in other skin areas. Histological examination showed an intraepidermal blister with acantholysis and necrosis of individual keratinocytes. Direct immunofluorescence and indirect immunofluorescence were typical of pemphigus. Immunoblot revealed antibodies reacting with a 110 kDa antigen. This feature was consistent with the diagnosis of RIP. Less than 20 cases of RIP have been reported previously. Mean age at diagnosis was 64.2 years, and there is a slight female preponderance. RIP occurred, in most cases, initially within the area of irradiation. CONCLUSION: Our patient showed some distinctive findings never reported previously in RIP: a histological focal keratinocyte necrosis, and the presence of autoantibodies reacting with a 110 kDa keratinocytic protein in immunoblot analysis. Because of a different prognosis, it is important to differentiate RIP and paraneoplastic pemphigus (PNP), although cases of ionizing radiation-induced PNP had also been described. As in our patient, RIP seems to respond well to systemic corticosteroids and immunosuppressive therapy, which induce remission within a few months. PMID- 22097993 TI - Pityriasis rubra pilaris: the clinical context of acantholysis and other histologic features. AB - BACKGROUND: Acantholysis has been described in biopsies of pityriasis rubra pilaris (PRP), but this has not been emphasized in the dermatology literature. It is helpful for dermatologists to associate acantholysis with PRP in the correct clinical setting. OBJECTIVE: This study aims to further elucidate the clinical context and associated histologic features of acantholysis in PRP. METHODS: Eight cases of PRP with acantholysis, 16 other cases of PRP, 26 cases of psoriasis, and 17 cases of erythroderma of different causes were studied in an academic setting. RESULTS: The presence of acantholysis initially confounded the diagnosis in two cases of PRP. Acantholysis was focal or extensive and resembled Darier's disease, Hailey-Hailey disease, or pemphigus vulgaris. Acantholysis was seen in biopsies from early, isolated papulosquamous lesions from the trunk as well as from erythroderma. By comparison, 26 cases of psoriasis and 17 cases of erythroderma showed only focal acantholysis in two cases of erythroderma. CONCLUSIONS: Acantholysis is a histologic feature of PRP and can serve as a histologic clue to the diagnosis of PRP before the onset of erythroderma. Eosinophils and/or a lichenoid infiltrate may also be evident. PMID- 22097994 TI - Correlation and agreement of self-assessed and objective skin disease severity in a cross-sectional study of patients with acne, psoriasis, and atopic eczema. AB - BACKGROUND: Previous studies have shown variable correlation of patients' self assessed skin severity measures and clinician-assessed objective measures of severity. But, generally, correlation has not been as good as might be expected for conditions in which the objective physical extent of skin disease is apparent to the sufferer to an extent that is not applicable in many other diseases. METHODS: This paper reports agreement and correlation of self-assessed and objective severity measures in a study of 108 subjects with acne, psoriasis, or atopic eczema. The study was a cross-sectional study examining psychological associations of these skin diseases. Objective severity was assessed with the Leeds technique (acne), the Psoriasis Area and Severity Index, and Six Area Six Sign Atopic Dermatitis instruments. Agreement is a more appropriate measure than correlation in this situation and was measured with weighted kappa, while correlation was measured with Spearman's rank correlation. RESULTS: There was a modest correlation of rho = 0.46 and similarly very modest agreement of 0.35 (weighted kappa) of self-assessed and clinician-assessed disease severity. Furthermore, self-assessed (but not clinician-assessed) severity was statistically associated with psychological morbidity in this study; i.e. - depression, anxiety, and overall psychological morbidity. CONCLUSIONS: Clinicians should consider psychological sequelae of skin disease, not only in those with objectively more severe disease but in patients across the severity spectrum. Both observational and interventional studies of skin disease should include both clinician-assessed and self-assessed measures of severity among assessed variables. PMID- 22097995 TI - Linear sclerodermic lupus erythematosus, a distinct variant of linear morphea and chronic cutaneous lupus erythematous. AB - BACKGROUND: Overlap syndromes represent disorders that combine diagnostic criteria of two or more different connective tissue diseases. METHODS: We herein describe the case of a 34-year-old patient. RESULTS: Our patient developed a lesion on the scalp and forehead following Blaschko's line typical for linear morphea "en coup de sabre", while histopathological features were consistent with both chronic cutaneous lupus erythematosus and linear morphea, a cutaneous overlap syndrome previously described as linear sclerodermiform lupus erythematosus. The patient was given oral antimalarials in association with topical steroids and calcineurin inhibitors with good response. CONCLUSIONS: Knowledge of this peculiar cutaneous overlap syndrome is warranted, since its management and prognosis is probably different from classical linear morphea. PMID- 22097996 TI - Augmented diagnostic capability using videodermatoscopy on selected infectious and non-infectious penile growths. AB - BACKGROUND: A large variety of infectious and non-infectious penile growths may occur on the glans or shaft with variable clinical presentation. Although most of these penile growths can be diagnosed through medical history and clinical examination, small, single or early lesions may not be easily recognized or differentiated by their clinical features. Videodermatoscopy (VD) is a non invasive technique that has greatly improved the diagnostic accuracy for pigmented and non-pigmented skin disorders. MATERIALS AND METHODS: Selected cases of penile growths from our Genital Dermatology Clinic have been evaluated by VD in order to identify specific VD patterns. RESULTS: Pearly penile papules, Fordyce's spots, genital warts, molluscum contagiosum, angiokeratoma of Fordyce, and median raphe penile cysts were found to show specific VD features, which are described and analyzed in detail. CONCLUSIONS: VD offers the possibility to enhance diagnostic accuracy and aids in the differential diagnosis of selected infectious and non-infectious penile growths. In case of single or not clinically specific lesions, VD allows non-invasive recognition of specific patterns and features in order to make a more definitive diagnosis and to rule out clinically similar growths, thus avoiding biopsy and other invasive measures in some cases. PMID- 22097997 TI - Unusual and recently described cutaneous atrophic disorders. AB - Cutaneous atrophic conditions are typically caused by changes in the dermis or subcutaneous tissue, sometimes consisting of the loss of a single fiber type. Since a significant decrease of subepidermal tissue is necessary for these lesions to be macroscopically atrophic, many conditions may not be appreciated as atrophy in the clinical setting. Clinicians should be familiar with the common or classic disorders causing cutaneous atrophy; however, there are a few new or rarely described atrophic conditions which are more difficult to identify and may not be atrophic clinically. This paper serves to describe the salient clinical and histological features of these new or rare disorders. PMID- 22097998 TI - Interesting effect of Malassezia spp. infection on dermatoses of other origins. AB - BACKGROUND: Tinea versicolor (TV) is a superficial fungal infection affecting as many as 40% of the population in the tropics. We noticed an unusual affect of TV on dermatoses of other origins. METHODS: In this prospective clinical study, we examined patients attending our dermatology outpatient department over a period of one year for coexistence of TV with any unrelated dermatoses. We confirmed the diagnosis of TV by microscopy of skin scrapings. Skin biopsy was performed when necessary to confirm the diagnosis of associated dermatoses. RESULTS: We describe four cases in which unrelated dermatoses (viral exanthem, acute generalized exanthematous pustulosis, polymorphous light eruption, and irritant contact dermatitis) specifically spared sites affected with TV. CONCLUSIONS: Recent research has elucidated the immunomodulatory properties of Malassezia spp. in vitro. Our cases serve as possible in vivo models illustrating such properties. Further studies based on these reports could lead to the isolation of molecules from Malassezia, which may have potential use in anti-inflammatory drug formulations. PMID- 22097999 TI - Diagnosing leprosy: revisiting the role of the slit-skin smear with critical analysis of the applicability of polymerase chain reaction in diagnosis. AB - BACKGROUND: Diagnosing leprosy is challenging, especially in early-stage cases, and the need for a sensitive diagnostic tool is urgent. Polymerase chain reaction (PCR) holds promise as a simple and sensitive diagnostic tool, but its usefulness in the Indian context requires further evaluation. Slit-skin smear (SSS) remains the conventional method of leprosy detection. Hence, this study was undertaken to evaluate and compare the diagnostic efficacy of PCR versus that of SSS. METHODS: Punch biopsy of skin and SSS were obtained from the active margins of lesions. Cases were clinically grouped according to whether they were multibacillary (MB) or paucibacillary (PB) and classified into tuberculoid (TT), borderline tuberculoid (BT), borderline lepromatous (BL), lepromatous (LL), histoid, and indeterminate groups after clinicopathological correlation. DNA was extracted from biopsy specimens, and multiplex PCR was carried out incorporating primers intended for the amplification of a specific 372-bp fragment of a repetitive sequence of Mycobacterium leprae DNA. RESULTS: Among 164 patients, PCR was positive in 82.3%. The sensitivity of PCR was significantly greater (P < 0.0001) than that of SSS in both the MB (85.9% vs. 59.8%) and PB (75.4% vs. 1.8%) subgroups; the difference in sensitivity in the PB subgroup is remarkable. Positivity by PCR and SSS was found in 100% of LL and histoid leprosy, but PCR had significantly greater (P < 0.0001) positivity in BT leprosy and was of definite increased value in indeterminate and TT leprosy. CONCLUSIONS: Polymerase chain reaction had higher sensitivity compared with SSS, especially in diagnostically challenging and PB cases. Thus, the use of this costly but sensitive tool should be restricted to this subgroup, because SSS is sufficiently sensitive in the diagnosis of LL and histoid leprosy. PMID- 22098000 TI - A morbilliform variant of linear IgA dermatosis: a new case. PMID- 22098001 TI - Adult colloid milium: a case report and literature review. PMID- 22098002 TI - Diffuse polymorphic eosinophilic cellulitis in a patient with metallic alloy implants: a possible association? PMID- 22098003 TI - Successful treatment of leg ulcer caused by cryofibrinogenemia by using a systemic corticosteroid and warfarin. PMID- 22098004 TI - Canine melanoma: a comparison with human pigmented epithelioid melanocytoma. PMID- 22098005 TI - Progressive nodular histiocytosis: a case report and literature review. PMID- 22098006 TI - Multiple squamous cell carcinomas in the setting of psoriasis treated with etanercept: a report of four cases and review of the literature. AB - BACKGROUND: Psoriasis is a common, chronic, hyperproliferative disease of the skin characterized by overexpression of type 1 cytokines, including tumor necrosis factor alpha. There is concern that antitumor necrosis factor agents such as etanercept may increase the incidence of cutaneous malignancies; however, the data are conflicting. Our objective was to further understand the characteristics and association of squamous cell carcinoma (SCC) development in patients with psoriasis who used etanercept. METHODS: Four patients with psoriasis were identified as having SCCs in the setting of etanercept. The histories of these patients were reviewed retrospectively. RESULTS: All four patients had lifelong psoriasis. The mean time of SCC onset was 11 months after etanercept therapy was begun (range, 1-17 months), and the number of SCCs in each patient ranged from five to more than 50. CONCLUSIONS: Currently, reports are conflicting about the effect of etanercept on SCC development. We present the first case series of patients in whom SCC developed in the setting of etanercept therapy. More research is needed to better characterize the effects of etanercept on the development and behavior of SCC in patients with psoriasis. PMID- 22098007 TI - A method for distinguishing the intended margins for a melanoma from the tissue cones after surgical excision. AB - BACKGROUND: Surgical excision of severely dysplastic nevi and thin cutaneous melanomas (<1 mm in depth) remains the most effective treatment to date. However, sometimes a severely dysplastic nevus may be upstaged to a melanoma in situ, or a melanoma in situ may be upgraded to an invasive melanoma once the completely excised specimen is reviewed microscopically. This then requires a re-excision around the entire scar at follow-up as the dermatological surgeon can be perplexed as to where the precise locations of the pigmented lesion and the tissue cones are, thereby generating a longer scar. OBJECTIVE: We want to introduce a simple, cost-effective and easy-to-implement approach that permits the dermatological surgeon to distinguish from a linear scar the site of the original pigmented lesion and the lengths of the tissue cones. Therefore, if a re excision is necessary, instead of surgical removal around the entire scar, only a focal directed excision of the pigmented lesion is necessary and this will result in a shorter scar; this will be useful for cosmetically sensitive areas on the face. A case is included to illustrate our objective. RESULTS AND DISCUSSION: Using our surgical method on a patient's left cheek pigmented lesion originally diagnosed as melanoma in situ with a subsequent revised diagnosis of invasive melanoma generated a shorter scar and a favorable cosmetic outcome. PMID- 22098008 TI - Effect of isotretinoin treatment on plasma holotranscobalamin, vitamin B12, folic acid, and homocysteine levels: non-controlled study. AB - Isotretinoin (Iso) has been used for the treatment of acne. Some previous studies reported elevated homocysteine (Hcy) levels after treatment with Iso. Some side effects have clinical presentations similar to vitamin B12, folic acid deficiencies, and hyperhomocysteinemia. In the present study we evaluated the plasma Hcy levels, the vitamins involved in its metabolism (vitamin B12 and folic acid), and holotranscobalamin (HoloTC), a transport system for vitamin B12 absorption in patients receiving Iso treatment for acne vulgaris. A total of 66 patients with acne vulgaris between the ages of 18 and 40 years were included. Screening for hemoglobin, creatinine, SGOT, SGPT, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C), folic acid, vitamin B12, Hcy, and HoloTC were done just before initiation (pretreatment) and after four months of Iso treatment (posttreatment). Posttreatment vitamin B12, folic acid, and HoloTC levels were significantly lower while Hcy levels were significantly higher compared with initial values. Posttreatment total cholesterol, LDL-C, triglycerides, VLDL-C, SGPT, and SGOT levels were also higher, and HDL-C levels were lower compared with initial values while there was no change in hemoglobin levels during Iso treatment. We found that Iso usage might cause decreased vitamin B12, folic acid, and HoloTC. These Iso side effects might contribute to the missing link between Iso usage, hyperhomocysteinemia, and neuropsychiatric disorders. Trials may be made with the aim of demonstrating (clearly) if starting vitamin B12 and folic acid replacement therapies with Iso treatment initialization could be useful for preventing hyperhomocysteinemia and possibly related disorders. PMID- 22098009 TI - Hematological abnormalities and the use of granulocyte-colony-stimulating factor in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. AB - BACKGROUND: Derangements in blood cell counts have been described in patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) but are not well characterized. We aim to describe the relationship between our patients' hematological results and the evolution of disease and hypothesize on the possible roles of granulocyte-colony-stimulating factor (G-CSF) in the management of these conditions. MATERIALS AND METHODS: Clinical records of our patients with SJS and TEN from January 2005 to 2010 were analyzed. RESULTS: Anemia and lymphopenia were most commonly seen, while thrombocytopenia was uncommon. Leukopenia and neutropenia were seen in patients with more severe disease, and the trend of leukopenia and neutropenia followed the evolution of disease. Two patients received G-CSF for febrile neutropenia and had a rapid recovery of their neutrophil counts as well as a shorter time to re-epithelialization. CONCLUSION: Our patients tended to have leukopenia and neutropenia that followed a predictable trend of decline and subsequent improvement depending on the stage of disease. This may be of pathogenic significance, and G-CSF may be used in these cases to manage febrile neutropenia and aid re-epithelialization. Further basic science research is required to prove our hypotheses. PMID- 22098010 TI - Mucosal psoriasis: a new insight toward a systemic inflammatory disease. PMID- 22098011 TI - On granulomatous hypersensitivity. PMID- 22098013 TI - Pseudoacne of the nasal crease in a 10-year-old boy. PMID- 22098012 TI - Palisaded neutrophilic granulomatous dermatitis caused by cellulitis in a patient with systemic lupus erythematosus. PMID- 22098014 TI - Unusual excessive xanthogranuloma in an adult. PMID- 22098015 TI - Prurigo nodularis as the first manifestation of a chronic autoimmune cholestatic hepatitis. PMID- 22098016 TI - 66th Annual Congress, Brazilian Society of Dermatology, Florianopolis, August 3 6, 2011. PMID- 22098018 TI - Deep brain stimulation in Pantothenate Kinase Associated Neurodegeneration: challenges for the future. PMID- 22098019 TI - Infliximab or cyclosporine for acute severe ulcerative colitis: a retrospective analysis. AB - BACKGROUND AND AIM: Medical treatment of steroid-refractory ulcerative colitis (UC) is limited to either cyclosporine or infliximab. Studies comparing cyclosporine with either placebo or intravenous methylprednisone showed promise for cyclosporine, but associated it with significant toxicity. There is conflicting, but increasingly positive evidence for using infliximab. There are no studies directly comparing these two treatments. Our aim was to compare the outcomes of patients with steroid-refractory UC treated with either intravenous cyclosporine or infliximab. METHODS: We carried out a retrospective review of inpatients with steroid-refractory UC, treated with either intravenous cyclosporine or infliximab, at Waitemata District Health Board, between January 2001 and February 2010. The primary end-points were time to colectomy, and colectomy rates at 3 and 12 months. Secondary end-points were time to discharge from initiation of treatment, steroid dependence at 12 months, and reported adverse events. RESULTS: The total study population was 38, with 19 in the infliximab group. Follow up to 12 months was complete in all patients. At 3 months, the colectomy rate was 63% for cyclosporine, compared to 21% (P = 0.0094). By 12 months the rate was 68% and 37% for cyclosporine and infliximab, respectively (P = 0.06). Patients in the cyclosporine group required an additional 5 days in hospital (P = 0.0086). Steroid dependence at 12 months was 50% for cyclosporine versus 25% for infliximab (P = 0.36). Cyclosporine caused more adverse events (P = 0.17). CONCLUSIONS: Infliximab improved clinical outcomes compared to the previous use of intravenous cyclosporine in patients admitted with steroid-refractory acute severe UC. PMID- 22098020 TI - Creation of bioorthogonal redox systems depending on nicotinamide flucytosine dinucleotide. AB - Many enzymes catalyzing biological redox chemistry depend on the omnipresent cofactor, nicotinamide adenine dinucleotide (NAD). NAD is also involved in various nonredox processes. It remains challenging to disconnect one particular NAD-dependent reaction from all others. Here we present a bioorthogonal system that catalyzes the oxidative decarboxylation of l-malate with a dedicated abiotic cofactor, nicotinamide flucytosine dinucleotide (NFCD). By screening the multisite saturated mutagenesis libraries of the NAD-dependent malic enzyme (ME), we identified the mutant ME-L310R/Q401C, which showed excellent activity with NFCD, yet marginal activity with NAD. We found that another synthetic cofactor, nicotinamide cytosine dinucleotide (NCD), also displayed similar activity with the ME mutants. Inspired by these observations, we mutated d-lactate dehydrogenase (DLDH) and malate dehydrogenase (MDH) to DLDH-V152R and MDH-L6R, respectively, and both mutants showed fully active with NFCD. When coupled with DLDH-V152R, ME-L310R/Q401C required only a catalytic amount of NFCD to convert l malate. Our results opened the window to engineer bioorthogonal redox systems for a wide variety of applications in systems biology and synthetic biology. PMID- 22098021 TI - Residues of sulfadiazine and doxycycline in broiler liver and muscle tissue due to cross-contamination of feed. AB - Veterinary drugs, such as antimicrobial compounds, are widely used in poultry and may lead to the presence of residues in matrices of animal origin, such as muscle and liver tissue. In this study, broilers received an experimental feed containing sulfadiazine or doxycycline at cross-contamination levels of 2.5, 5 and 10% of the therapeutic dose in feed. Breast and thigh muscle and liver samples were collected during treatment and depletion period and analysed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations reached a plateau phase 3-5 days after the start of experimental feeding. A rapid depletion of residues was noted after withdrawal of the experimental feed. No significant differences in measured concentrations were observed between the various muscle types. Residue concentrations for some experimental groups; the 10% group of sulfadiazine and the 5 and 10% group of doxycycline, however, exceeded their corresponding maximum residue limits (MRLs). PMID- 22098022 TI - Loss of implant-bone interface following distal radial locking-plate endoprosthesis limb-sparing surgery in a dog. AB - An eight-year-old, neutered female Rottweiler was presented with lameness of seven days duration. Radiographs were consistent with a distal radial bone tumour. Limb-sparing surgery was performed using a commercially available endoprosthesis with a locking bone plate. Histopathological examination of the resected bone revealed an intraosseous fibrosarcoma, and postoperative adjuvant chemotherapy was initiated three weeks after surgery. Despite initial satisfactory limb function, lameness worsened four months after surgery. Radiographs revealed large areas of bone lysis around the proximal and distal screws, leading to significant resorption of the radius and radial carpal bone with subsequent construct failure. Further treatment was declined by the owner and the dog was subsequently euthanased. This case illustrates that implant failure is not necessarily averted by the use of locking (compared with non locking) implants combined with an endoprosthesis to treat distal radial tumours in dogs. PMID- 22098030 TI - Infectious mononucleosis and monoclonal B lymphocytosis in an elderly man. PMID- 22098031 TI - Subjective quality of life in older community-dwelling adults in the kingdom of Bhutan and Japan. PMID- 22098032 TI - Fifteen-item geriatric depression scale predicts 8-year mortality in older Japanese. PMID- 22098033 TI - A new crisis in Japan-social isolation in old age. PMID- 22098034 TI - Physiologically relaxing effect of a hospital rooftop forest on older women requiring care. PMID- 22098035 TI - Self-neglect and elder abuse: related phenomena? PMID- 22098029 TI - Review: molecular pathology in adult high-grade gliomas: from molecular diagnostics to target therapies. AB - The classification of malignant gliomas is moving from a morphology-based guide to a system built on molecular criteria. The development of a genomic landscape for gliomas and a better understanding of its functional consequences have led to the development of internally consistent molecular classifiers. However, development of a biologically insightful classification to guide therapy is still a work in progress. Response to targeted treatments is based not only on the presence of drugable targets, but rather on the molecular circuitry of the cells. Further, tumours are heterogeneous and change and adapt in response to drugs. Therefore, the challenge of developing molecular classifiers that provide meaningful ways to stratify patients for therapy remains a major challenge for the field. In this review, we examine the potential role of MGMT methylation, IDH1/2 mutations, 1p/19q deletions, aberrant epidermal growth factor receptor and PI3K pathways, abnormal p53/Rb pathways, cancer stem-cell markers and microRNAs as prognostic and predictive molecular markers in the setting of adult high-grade gliomas and we outline the clinically relevant subtypes of glioblastoma with genomic, transcriptomic and proteomic integrated analyses. Furthermore, we describe how these advances, especially in epidermal growth factor receptor/PI3K/mTOR signalling pathway, affect our approaches towards targeted therapy, raising new challenges and identifying new leads. PMID- 22098036 TI - Effectiveness of thrombolysis with intravenous alteplase for acute ischemic stroke in older adults. PMID- 22098037 TI - Depressive symptoms increase the risk of mortality in older Mexican community dwelling adults. PMID- 22098038 TI - A 5-year review of the immunization profile of older adults with liver disease at a community hospital. PMID- 22098039 TI - Heparin bridging therapy and bleeding events in octogenarian inpatients with atrial fibrillation starting anticoagulation: results of an ancillary study. PMID- 22098040 TI - Sicca syndrome in hospitalized older adults: prevalence and comparison of objective and subjective symptoms. PMID- 22098041 TI - Asymptomatic colonization by Clostridium difficile in older adults admitted to a geriatric unit: a prospective cohort study. PMID- 22098042 TI - Does memantine improve the gait of individuals with Alzheimer's disease? PMID- 22098043 TI - Quality of the rating of mini-mental state examination in a well-defined population of French general practitioners. PMID- 22098044 TI - Objective sleep duration and quality in hospitalized older adults: associations with blood pressure and mood. PMID- 22098045 TI - Geriatric MyHealth Passport: a pilot study of a portable health summary in an elderly population. PMID- 22098046 TI - Timed up and go test predicts cognitive decline in healthy adults aged 80 and older in Okinawa: Keys to Optimal Cognitive Aging (KOCOA) Project. PMID- 22098047 TI - Guidelines for non-medical care providers to detect illnesses in elderly evacuees after the 2011 earthquake off the Pacific coast of Tohoku. PMID- 22098048 TI - Gait velocity versus the timed up and go test: which one to use for the prediction of falls and other adverse health outcomes in primary care? PMID- 22098050 TI - Undiagnosed cognitive impairment in nursing home residents. PMID- 22098051 TI - Functional recovery after stroke. PMID- 22098053 TI - Addressing challenges of identifying geometrically diverse sets of crystalline porous materials. AB - Crystalline porous materials have a variety of uses, such as for catalysis and separations. Identifying suitable materials for a given application can, in principle, be done by screening material databases. Such a screening requires automated high-throughput analysis tools that calculate topological and geometrical parameters describing pores. These descriptors can be used to compare, select, group, and classify materials. Here, we present a descriptor that captures shape and geometry characteristics of pores. Together with proposed similarity measures, it can be used to perform diversity selection on a set of porous materials. Our representations are histogram encodings of the probe accessible fragment of the Voronoi network representing the void space of a material. We discuss and demonstrate the application of our approach on the International Zeolite Association (IZA) database of zeolite frameworks and the Deem database of hypothetical zeolites, as well as zeolitic imidazolate frameworks constructed from IZA zeolite structures. The diverse structures retrieved by our method are complementary to those expected by emphasizing diversity in existing one-dimensional descriptors, e.g., surface area, and similar to those obtainable by a (subjective) manual selection based on materials' visual representations. Our technique allows for reduction of large sets of structures and thus enables the material researcher to focus efforts on maximally dissimilar structures. PMID- 22098054 TI - Round window membrane motion before and after stapedotomy surgery - an experimental study. AB - This paper presents the results of non-contact measurements of the human ear round window (RW) membrane motion in freshly harvested human cadaver temporal bone specimens. A PSV 400 Scanning Laser Vibrometer system (Polytec, Waldbronn, Germany) was used to determine the effect of stapedotomy on the sound-induced displacement amplitude of the RW membrane. The vibration patterns were measured in the frequency range of 0.4-10 kHz in four specimens with air conduction stimulation at 90 dB SPL applied to the external auditory canal. It was shown that the vibration amplitude of the RW membrane after stapes piston prosthesis implantation, in comparison with a physiological specimen, was reduced several times. The motion of the RW membrane can be used to determine the cochlear stimulation for the evaluation of middle ear ossicle reconstruction, especially in the case of otosclerosis surgery. PMID- 22098056 TI - Effect of denture adhesive on the micro-organisms in vivo. AB - BACKGROUND: Denture adhesives increase the retention and stability of dentures in edentulous patients, especially in cases where salivary flow is impaired or in the management of traumatised oral mucosa. OBJECTIVES: The effect of a denture adhesive on the oral flora at different time intervals. METHOD: Thirty denture wearing patients were involved in this study. While half of the group received a denture adhesive, the other half did not. At baseline, 1 and 2 months after delivering the dentures, smear samples were obtained from the saliva, palate and the dentures. Candida albicans, Candida krusei, Candida glabrata, Candida spp., Staphylococcus aureus, Moraxella catarrhalis, alpha-haemolytic streptococci, beta haemolytic streptococci, Pneumococcus aureus, S. anginosus, S. intermedius, S. constellatus, S. sanguis, S. gordonii, S. mitis, S. mutans, S. salivarius, and yeasts were investigated. The data were statistically analysed using anova and repeated measures. RESULTS: Most types of the micro-organisms were not seen and could not be analysed statistically except alpha-haemolytic streptococci and C. albicans. No statistically significant difference was found for alpha-haemolytic streptococci and C. albicans in saliva, palate and the denture at all time intervals. CONCLUSIONS: Prolonged use of the denture adhesive tested up to 2 months did not yield to increase in micro-organisms of the oral flora. PMID- 22098057 TI - Structure and property engineering of alpha-D-glucans synthesized by dextransucrase mutants. AB - Seven dextran types, displaying from 3 to 20% alpha(1->3) glycosidic linkages, were synthesized in vitro from sucrose by mutants of dextransucrase DSR-S from Leuconostoc mesenteroides NRRL B-512F, obtained by combinatorial engineering. The structural and physicochemical properties of these original biopolymers were characterized. When asymmetrical flow field flow fractionation coupled with multiangle laser light scattering was used, it was determined that weight average molar masses and radii of gyration ranged from 0.76 to 6.02 * 10(8) g.mol(-1) and from 55 to 206 nm, respectively. The nu(G) values reveal that dextrans Gcn6 and Gcn7, which contain 15 and 20% alpha(1->3) linkages, are highly branched and contain long ramifications, while Gcn1 is rather linear with only 3% alpha(1->3) linkages. Others display intermediate molecular structures. Rheological investigation shows that all of these polymers present a classical non-Newtonian pseudoplastic behavior. However, Gcn_DvDelta4N, Gcn2, Gcn3, and Gcn7 form weak gels, while others display a viscoelastic behavior that is typical of entangled polymer solutions. Finally, glass transition temperature T(g) was measured by differential scanning calorimetry. Interestingly, the T(g) of Gcn1 and Gcn5 are equal to 19.0 and 29.8 degrees C, respectively. Because of this low T(g), these two original dextrans are able to form rubber and flexible films at ambient temperature without any plasticizer addition. The mechanical parameters determined for Gcn1 films from tensile tests are very promising in comparison to the films obtained with other polysaccharides extracted from plants, algae or microbial fermentation. These results lead the way to using these dextrans as innovative biosourced materials. PMID- 22098058 TI - A rural undergraduate campus in England: virtue from opportunity and necessity. AB - The implementation of new curriculum at Keele University Medical School, UK has made heavy use of general practice as a locus for learning. This has necessitated a substantial expansion in the School's teaching network. The School's hinterland includes a large rural area with a number of excellent general practices and associated community hospitals that, to date, have been unable to teach undergraduates because of their inaccessibility. This article describes how the School and its partners articulated a vision to establish a rural campus with an associated rural accommodation hub, and the challenges involved in establishing and sustaining the campus. PMID- 22098059 TI - Diaphragmatic tear in pregnancy induced by intractable vomiting: a case report and review of the literature. AB - OBJECTIVE: Nausea and vomiting of pregnancy, the most common medical condition of pregnancy, affects up to 80% of all pregnancies to some extent, and hyperemesis gravidarum does less than 1% of pregnant women. When hyperemesis gravidarum induces diaphragmatic tear, diagnosis can be missed because of nonspecific presentation with abdominal pain, nausea and vomiting. METHODS: We reported a pregnant case suffering from intractable vomiting at the beginning of the second trimester (the 13th week of gestation) with delayed diagnosis of diaphragmatic tearing. RESULTS: The patient was misdiagnosed initially, which delayed the surgical intervention and unnecessary abortion. CONCLUSION: It is worthwhile considering the maternal diaphragmatic cause as an unusual one of refractory vomiting accompanied by clinically significant progressive epigastric pain, distension and respiratory embarrassment. PMID- 22098060 TI - Biomolecule-recognition gating membrane using biomolecular cross-linking and polymer phase transition. AB - We present for the first time a biomolecule-recognition gating system that responds to small signals of biomolecules by the cooperation of biorecognition cross-linking and polymer phase transition in nanosized pores. The biomolecule recognition gating membrane immobilizes the stimuli-responsive polymer, including the biomolecule-recognition receptor, onto the pore surface of a porous membrane. The pore state (open/closed) of this gating membrane depends on the formation of specific biorecognition cross-linking in the pores: a specific biomolecule having multibinding sites can be recognized by several receptors and acts as the cross linker of the grafted polymer, whereas a nonspecific molecule cannot. The pore state can be distinguished by a volume phase transition of the grafted polymer. In the present study, the principle of the proposed system is demonstrated using poly(N-isopropylacrylamide) as the stimuli-responsive polymer and avidin-biotin as a multibindable biomolecule-specific receptor. As a result of the selective response to the specific biomolecule, a clear permeability change of an order of magnitude was achieved. The principle is versatile and can be applied to many combinations of multibindable analyte-specific receptors, including antibody antigen and lectin-sugar analogues. The new gating system can find wide application in the bioanalytical field and aid the design of novel biodevices. PMID- 22098061 TI - Unravelling the peculiarities of island life: vicariance, dispersal and the diversification of the extinct and extant giant Galapagos tortoises. AB - In isolated oceanic islands, colonization patterns are often interpreted as resulting from dispersal rather than vicariant events. Such inferences may not be appropriate when island associations change over time and new islands do not form in a simple linear trend. Further complexity in the phylogeography of ocean islands arises when dealing with endangered taxa as extinctions, uncertainty on the number of evolutionary 'units', and human activities can obscure the progression of colonization events. Here, we address these issues through a reconstruction of the evolutionary history of giant Galapagos tortoises, integrating DNA data from extinct and extant species with information on recent human activities and newly available geological data. Our results show that only three of the five extinct or nearly extinct species should be considered independent evolutionary units. Dispersal from mainland South America started at approximately 3.2 Ma after the emergence of the two oldest islands of San Cristobal and Espanola. Dispersal from older to younger islands began approximately 1.74 Ma and was followed by multiple colonizations from different sources within the archipelago. Vicariant events, spurred by island formation, coalescence, and separation, contributed to lineage diversifications on Pinzon and Floreana dating from 1.26 and 0.85 Ma. This work provides an example of how to reconstruct the history of endangered taxa in spite of extinctions and human mediated dispersal events and highlights the need to take into account both vicariance and dispersal when dealing with organisms from islands whose associations are not simply explained by a linear emergence model. PMID- 22098062 TI - Screening of de novo tumors after liver transplantation. AB - De novo malignancies are frequent complications after liver transplantation. They are one of the leading causes of late death. Some authors have reported promising results following implementation of extensive cancer surveillance programs. Screening protocols might benefit patients by providing a diagnosis at an earlier stage when tumors may be cured. These protocols should be based on the specific risk factors of every patient. Unfortunately, the scientific evidence supporting screening protocols is still very weak both in the general population and in the transplant patients. On this basis, there is not enough evidence to recommend routine screening for all liver transplant recipients, apart from the recommendations accepted for the general population. Multicenter studies in selected groups of patients at high risk for malignancy may be the only way of defining the potential benefit of screening programs post-transplantation. PMID- 22098063 TI - High level use and satisfaction with internet-based breast cancer survivorship care plans. PMID- 22098064 TI - Tenofovir plus entecavir as rescue therapy for multidrug-resistant chronic hepatitis B. PMID- 22098065 TI - Clinical and pharmacokinetic evaluation of satraplatin. AB - INTRODUCTION: The toxicities of cisplatin, that is, nephrotoxicity, neurotoxicity and emesis, provided the impetus for the development of more tolerable platinum analogs. Satraplatin is an investigational third-generation orally available lipophilic platinum, which has demonstrated safety and antitumor activity in multiple settings. AREAS COVERED: The clinical activity of satraplatin in metastatic castrate-resistant prostate cancer (mCRPC), breast, lung and other advanced solid tumors is discussed with a focus on its pharmacokinetic properties. The article was formulated using publications found through PubMed search in addition to presentations given at major conferences. EXPERT OPINION: Satraplatin was associated with dose-limiting myelosuppression, but no significant ototoxicity, neurotoxicity or nephrotoxicity. Despite the activity of satraplatin in mCRPC, survival was not extended in an unselected population included in a Phase III trial. While further development of satraplatin in large Phase III trials is not planned at this time, efforts are ongoing to develop tailored therapy in mCRPC based on excision repair cross-complementing group 1 expression or BRCAness. Moreover, based on potentially better central nervous system penetration due to lipophilicity, evaluation in patients with brain tumors is ongoing. Given the favorable toxicity profile and convenient oral administration, satraplatin may warrant development in settings that preclude cisplatin, for example, underlying renal dysfunction, elderly age and poor performance status. PMID- 22098066 TI - Probing side-chain dynamics in proteins by the measurement of nine deuterium relaxation rates per methyl group. AB - We demonstrate the feasibility of the measurement of up to nine deuterium spin relaxation rates in 13CHD2 and 13CH2D methyl isotopomers of small proteins. In addition to five measurable 2H relaxation rates in a 13CH2D methyl group (Millet, O.; Muhandiram, D. R.; Skrynnikov, N. R.; Kay, L. E. J. Am. Chem. Soc. 2002, 124, 6439-48), the measurement of additional four rates of (nearly) single exponentially decaying magnetization terms in methyl groups of the 13CHD2 variety is reported. Consistency relationships between 2H spin relaxation rates measured in the two different types of methyl groups are derived and verified experimentally for a subset of methyl-containing side chains in the protein ubiquitin. A detailed comparison of methyl-bearing side-chain dynamics parameters obtained from relaxation measurements in 13CH2D and 13CHD2 methyls of ubiquitin at 10, 27, and 40 degrees C reveals that transverse 2H relaxation rates in 13CHD2 groups are reliable and accurate reporters of the amplitudes of methyl 3 fold axis motions (S(axis)2) for protein molecules with global molecular tumbling times tau(C) >~9 ns. For smaller molecules, simple correction of transverse 2H relaxation rates in 13CHD2 groups is sufficient for the derivation of robust measures of order. Residue-specific distributions of S(axis)2 are consistent with atomic-detail molecular dynamics (MD) results. Both 13CHD2- and 13CH2D-derived S(axis)2 values are in good overall agreement with those obtained from 1 MUs MD simulations at all the three temperatures, although some differences in the site specific temperature dependence between MD- and 2H-relaxation-derived S(axis)2 values are observed. PMID- 22098067 TI - The currently used commercial DNA-extraction methods give different results of clostridial and actinobacterial populations derived from human fecal samples. AB - Recently several human health-related microbiota studies have had partly contradictory results. As some differences may be explained by methodologies applied, we evaluated how different storage conditions and commonly used DNA extraction kits affect bacterial composition, diversity, and numbers of human fecal microbiota. According to our results, the DNA-extraction did not affect the diversity, composition, or quantity of Bacteroides spp., whereas after a week's storage at -20 degrees C, the numbers of Bacteroides spp. were 1.6-2.5 log units lower (P < 0.05). Furthermore, the numbers of predominant bacteria, Eubacterium rectale (Erec)-group, Clostridium leptum group, bifidobacteria, and Atopobium group were 0.5-4 log units higher (P < 0.05) after mechanical DNA-extraction as detected with qPCR, regardless of storage. Furthermore, the bacterial composition of Erec-group differed significantly after different DNA-extractions; after enzymatic DNA-extraction, the most prevalent genera detected were Roseburia (39% of clones) and Coprococcus (10%), whereas after mechanical DNA-extraction, the most prevalent genera were Blautia (30%), Coprococcus (13%), and Dorea (10%). According to our results, rigorous mechanical lysis enables detection of higher bacterial numbers and diversity from human fecal samples. As it was shown that the results of clostridial and actinobacterial populations are highly dependent on the DNA-extraction methods applied, the use of different DNA-extraction protocols may explain the contradictory results previously obtained. PMID- 22098069 TI - Identification of a galactose-specific flocculin essential for non-sexual flocculation and filamentous growth in Schizosaccharomyces pombe. AB - Although various mutant strains of the fission yeast Schizosaccharomyces pombe exhibit non-sexual flocculation, little is known about the mechanistic basis for this phenomenon, nor have genes encoding the implicated flocculin been identified. In the budding yeast Saccharomyces cerevisiae, the transcription factor Flo8 controls expression of some of the genes involved in non-sexual flocculation. We have found that overexpression of S. cerevisiae FLO8 induced non sexual flocculation in S. pombe. This non-sexual flocculation was Ca(2+) dependent, and was inhibited by addition of galactose, but not by mannose, glucose or sucrose. In the FLO8-overexpressing strain, a gene designated gsf2(+) (galactose-specific flocculation) was specifically induced. The gsf2(+) gene was also highly expressed in lkh1Delta, tup12Delta and gsf1 mutants, all of which exhibited non-sexual flocculation dependent on gsf2(+) . We show that the N terminal region of Gsf2 recognizes galactose in mediating cell-cell interaction. Disruption of gsf2(+) also abolished the adhesion phenotype and invasive growth of the wild-type strain cultured in low ammonium medium. The newly identified flocculin Gsf2 in fission yeast was not only required for non-sexual flocculation but was also required for adhesion and filamentous growth through recognition of galactose residues on cell surface glycoconjugates. PMID- 22098070 TI - Clinicians' views of formats of performance comparisons. AB - RATIONALE, AIMS AND OBJECTIVES: Comparisons of the performance of health care providers are increasingly being used. Despite one key audience being clinicians, there has been little research on the format and content of such comparisons. Our aim was to explore clinicians' comprehension and preferences of format and content in displaying provider outcomes using comparisons of patient reported outcome measures data. METHOD: A qualitative study, based on seven meetings involving 107 clinicians (mostly consultant and junior doctors, and nurses), revealed their views on nine formats and five aspects of content. RESULTS: Key findings were the desire for data in more than one format, explicit display of comparative performance (rank order) and the need for explanations (e.g. of unfamiliar formats and of statistical uncertainty). CONCLUSIONS: Several themes were identified that shaped clinicians' views. Results were sufficiently clear to permit recommendations for the form and content of standard reports for the National Health Service. PMID- 22098068 TI - Somatostatin stimulates the migration of hepatic oval cells in the injured rat liver. AB - BACKGROUND: Somatostatin is a pleiotropic peptide, exerting a variety of effects through its receptor subtypes. Recently, somatostatin has been shown to act as a chemoattractant for haematopoietic progenitor cells and hepatic oval cells (HOC) via receptor subtype 2 and subtype 4 (SSTR4) respectively. AIMS: We investigated the in vivo effect of somatostatin/SSTR4 on HOC migration in the injured liver model of rats and the type of signalling molecules associated with the chemotactic function. METHODS: Migration assay, HOC transplantation and phosphatidylinositol-3-kinase (PI3K) signalling were assessed with or without somatostatin and an analogue of somatostatin (TT232) that specifically binds to SSTR4. RESULTS: TT232 was shown to have an antimigratory action on HOC induced by somatostatin in vitro. In HOC transplantation experiments, a lower number of donor-derived cells were detected in TT232-treated animals, as compared with control animals. Activation of PI3K was observed in HOC exposed to somatostatin, and this activation was suppressed by either SSTR4 antibody or TT232 pretreatment. In addition, a PI3K inhibitor abrogated the motility of HOC. CONCLUSION: Together, these data suggest that somatostatin stimulates the migration of HOC within injured liver through SSTR4, and this action appears to be mediated by the PI3K pathway. PMID- 22098071 TI - Patients' profile, burden of disease and quality of life in recurrent herpes labialis: a survey conducted in USA and France. PMID- 22098072 TI - Retrospective evaluation of the use of amiodarone in dogs with arrhythmias (from 2003 to 2010). AB - OBJECTIVES: To evaluate the efficacy of amiodarone in dogs with refractory supraventricular and ventricular arrhythmias and to document the side effects in treated dogs. METHODS: Records of 28 dogs were retrospectively searched to document indication for amiodarone administration, heart rate, alkaline phosphatase, alanine aminotransferase, thyroxine (T4) and thyroid stimulating hormone values before and after starting treatment and during follow-up periods. RESULTS: Sixteen dogs with supraventricular and 12 dogs with ventricular arrhythmias were treated with amiodarone. Amiodarone treatment significantly reduced the heart rate (P<0.001) and resulted in improvement in the severity of the arrhythmia and clinical signs in 26 dogs. There were no significant differences in alkaline phosphatase (P=0.596), alanine aminotransferase (P=0.842), T4 (P=0.789) and thyroid stimulating hormone (P=0.064) before and after starting amiodarone. On maintenance therapy, median amiodarone blood levels were within the accepted reference range (0.5 to 2.0 mg/L) at 0.8 mg/L (range 0.2 to 11.6 mg/L), but the majority of the desethylamiodarone levels were below normal at 0.1 mg/L (range 0.1 to 0.9 mg/L), based on human reference intervals (0.5 to 2.0 mg/L). CLINICAL SIGNIFICANCE: Amiodarone may be an effective and safe alternative to treat supraventricular and ventricular arrhythmias in dogs, when common anti-arrhythmic drugs are not effective or contraindicated. PMID- 22098073 TI - Anatomy and functional role of the inferior longitudinal fasciculus: a search that has just begun. PMID- 22098075 TI - Baseline plasma levels of interleukin-8 in stage IV non-small-cell lung cancer patients: relationship with nutritional status and prognosis. AB - Interleukin (IL)-8 promotes cellular proliferation and angiogenesis in patients with non-small-cell lung cancer (NSCLC) and may be related to cachexia. Our aim was to investigate the relationship of IL-8 levels with nutritional status, and clinical outcome of patients with NSCLC. Patients with metastatic NSCLC referred for first-line therapy were eligible. Baseline IL-8 levels were measured in plasma. The Mini Nutritional Assessment (MNA) was used for the evaluation of the nutritional status, and patients were classified into 3 groups: A (score 24-30) "well nourished," B (score 17-23.5) "risk of malnutrition," and C (0-16.5) "malnourishment." Response to first-line chemotherapy, time-to-tumor progression (TTP), and overall survival (OS) were also recorded. In total, 114 patients (101 males, 88.5%; mean age = 67.5 yr) were evaluated. Performance status was 0-1 in 62% of the patients. According to the MNA, the majority of patients (71%) was either at nutritional risk or malnourished. IL-8 levels were significantly different between MNA groups (P = 0.023) and correlated with TTP (P = 0.013) and OS (P = 0.001) in univariate analysis. Baseline IL-8 levels correlate with the nutritional status of patients with metastatic NSCLC, suggesting that this cytokine may be related with cachexia. PMID- 22098076 TI - Diagnostic yield of dual-phase computed tomography enterography in patients with obscure gastrointestinal bleeding and a non-diagnostic capsule endoscopy. AB - BACKGROUND AND AIM: In patients with obscure gastrointestinal (GI) bleeding, capsule endoscopy is widely used to determine the source of bleeding. However, there is currently no consensus on how to further evaluate patients with obscure GI bleeding with a non-diagnostic capsule endoscopy examination. This study aims to determine the diagnostic yield of dual-phase computed tomographic enterography (CTE) in patients with obscure GI bleeding and a non-diagnostic capsule endoscopy. METHODS: Patients with obscure GI bleeding who were referred for capsule endoscopy were prospectively enrolled. Obscure GI bleeding was defined as overt if there was obvious GI bleeding; otherwise it was defined as occult. Patients with a non-diagnostic capsule endoscopy and no contraindications underwent a CTE. RESULTS: Capsule endoscopy was performed in 52 patients; 26 patients (50%) had occult GI bleeding and 26 patients (50%) had overt GI bleeding. CTE was then performed in 25 of the 48 patients without a definitive source of bleeding seen on capsule endoscopy. The diagnostic yield of CTE was 0% (0/11) in patients with occult bleeding versus 50% (7/14) in patients with overt bleeding (P < 0.01). Using clinical follow up as the gold standard, for the 25 patients with a non-diagnostic capsule, CTE had a sensitivity of 33% (95% confidence interval 0.15, 0.56) and a specificity of 75% (95% confidence interval 0.22, 0.99). CONCLUSIONS: In patients with a non-diagnostic capsule endoscopy examination, CTE is useful for detecting a source of GI bleeding in patients with overt, but not occult, obscure GI bleeding. PMID- 22098077 TI - Urotensin II levels in patients with chronic kidney disease and kidney transplants. AB - OBJECTIVE: Urotensin II is a potent vasoactive peptide that has been implicated in the pathophysiology of many diseases. There is no study reporting the role and level of this peptide in recipients of kidney transplant. So we aimed to study the plasma levels of urotensin II in this group of patients. METHODS: Plasma urotensin II levels were analyzed in 110 subjects, who were divided into three groups: group 1 (35 kidney transplant recipients), group 2 (36 patients with chronic kidney disease), and group 3 (39 healthy controls). RESULTS: Analysis of logarithmic transformation of urotensin II, i.e. log (urotensin II * 1000) levels, with a one-way analysis of variance yielded a P value of 0.001. Post-hoc analysis showed significantly higher log (urotensin II * 1000) levels in group 1 than groups 2 and 3 (P = 0.001 and 0.017, respectively). One of the important features of the subjects of this group was that they were taking immunosuppressive drugs because of renal transplantation. CONCLUSIONS: High urotensin II levels in recipients of kidney transplants could be drug-related (immunosuppressive drugs) and may be of practical importance that may be used to improve the long-term outcome of the patients. PMID- 22098078 TI - Homeless people as target population in the scientific investigation. PMID- 22098079 TI - Short communication: Phenotypic protease inhibitor resistance and cross resistance in the clinic from 2006 to 2008 and mutational prevalences in HIV from patients with discordant tipranavir and darunavir susceptibility phenotypes. AB - To test tipranavir (TPV) or darunavir (DRV) as treatment options for patients with phenotypic resistance to protease inhibitors (PIs), including lopinavir, saquinavir, atazanavir, and fosamprenavir, the PhenoSense GT database was analyzed for susceptibility to DRV or TPV among PI-resistant isolates. The Monogram Biosciences HIV database (South San Francisco, CA) containing 7775 clinical isolates (2006-2008) not susceptible to at least one first-generation PI was analyzed. Phenotypic responses [resistant (R), partially susceptible (PS), or susceptible (S)] were defined by upper and lower clinical cut-offs to each PI. Genotypes were screened for amino acid substitutions associated with TPV-R/DRV-S and TPV-S/DRV-R phenotypes. In all, 4.9% (378) of isolates were resistant to all six PIs and 31.0% (2407) were resistant to none. Among isolates resistant to all four first-generation PIs, DRV resistance increased from 21.2% to 41.9% from 2006 to 2008, respectively, and resistance to TPV remained steady (53.9 to 57.3%, respectively). Higher prevalence substitutions in DRV-S/TPV-R isolates versus DRV R/TPV-S isolates, respectively, were 82L/T (44.4% vs. 0%) and 83D (5.8% vs. 0%). Higher prevalence substitutions in DRV-R/TPV-S virus were 50V (0.0% vs. 28.9%), 54L (1.0% vs. 36.1%), and 76V (0.4% vs. 15.5%). Mutations to help predict discordant susceptibility to DRV and TPV in isolates with reduced susceptibility to other PIs were identified. DRV resistance mutations associated with improved virologic response to TPV were more prevalent in DRV-R/TPV-S isolates. TPV resistance mutations were more prevalent in TPV-R and DRV-S isolates. These results confirm the impact of genotype on phenotype, illustrating how HIV genotype and phenotype data assist regimen optimization. PMID- 22098080 TI - Drug effect prediction by polypharmacology-based interaction profiling. AB - Most drugs exert their effects via multitarget interactions, as hypothesized by polypharmacology. While these multitarget interactions are responsible for the clinical effect profiles of drugs, current methods have failed to uncover the complex relationships between them. Here, we introduce an approach which is able to relate complex drug-protein interaction profiles with effect profiles. Structural data and registered effect profiles of all small-molecule drugs were collected, and interactions to a series of nontarget protein binding sites of each drug were calculated. Statistical analyses confirmed a close relationship between the studied 177 major effect categories and interaction profiles of ca. 1200 FDA-approved small-molecule drugs. On the basis of this relationship, the effect profiles of drugs were revealed in their entirety, and hitherto uncovered effects could be predicted in a systematic manner. Our results show that the prediction power is independent of the composition of the protein set used for interaction profile generation. PMID- 22098081 TI - Identifying individual cell types in heterogeneous cultures using secondary ion mass spectrometry imaging with C60 etching and multivariate analysis. AB - Tissue engineering approaches fabricate and subsequently implant cell-seeded and unseeded scaffold biomaterials. Once in the body, these biomaterials are repopulated with somatic cells of various phenotypes whose identification upon explantation can be expensive and time-consuming. We show that imaging time-of flight secondary ion mass spectrometry (TOF-SIMS) can be used to distinguish mammalian cell types in heterogeneous cultures. Primary rat esophageal epithelial cells (REEC) were cultured with NIH 3T3 mouse fibroblasts on tissue culture polystyrene and freeze-dried before TOF-SIMS imaging. Results show that a short etching sequence with C(60)(+) ions can be used to clean the sample surface and improve the TOF-SIMS image quality. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were used to identify peaks whose contributions to the total variance in the multivariate model were due to either the two cell types or the substrate. Using PLS-DA, unknown regions of cellularity that were otherwise unidentifiable by SIMS could be classified. From the loadings in the PLS-DA model, peaks were selected that were indicative of the two cell types and TOF-SIMS images were created and overlaid that showed the ability of this method to distinguish features visually. PMID- 22098083 TI - The role of metacognitive beliefs in stress sensitisation, self-esteem variability, and the generation of paranoia. AB - INTRODUCTION. Stress sensitisation may play a key role in the formation of psychosis. The authors examined whether metacognitive beliefs and self-esteem moderate affective response to stress, and whether subtle fluctuations in self esteem act as a mediator between stress and attenuated psychotic phenomena. METHOD. 70 healthy volunteers completed two conditions of the same experimental tasks, which were designed to be either neutral or stress inducing. Ambulant assessments of negative affect, self-esteem, and suspicious thoughts were taken before and after each task, and standardised questionnaires were completed at the beginning or end of each session. RESULTS. Metacognitive belief subscales, but not self-esteem, moderated the association between stress and resultant negative affect, and negative affect and suspicious thinking. Individuals who placed greater emphasis on controlling their thoughts had greater variability in their self-esteem during the stress condition, which in turn predicted the severity of their attenuated psychotic phenomena. DISCUSSION. Metacognitive beliefs may sensitise an individual to minor stressors, by increasing affective reactivity and causing subtle shifts in appraisals of self-worth. Psychosocial intervention may wish to target these beliefs in order to desensitise an individual to negative events. PMID- 22098087 TI - Synthesis of metal-organic frameworks (MOFs): routes to various MOF topologies, morphologies, and composites. PMID- 22098088 TI - Synthesis of (+)-ambrisentan via chiral ketone-catalyzed asymmetric epoxidation. AB - The synthesis of optically pure (+)-ambrisentan has been achieved from 3,3 diphenylacrylate in four steps with 53% overall yield and >99% ee at the >100 g scale without column purification. The chiral epoxide intermediate was prepared via asymmetric epoxidation with a fructose-derived diacetate ketone as catalyst. PMID- 22098089 TI - Construction-conditioned rollback in total knee replacement: fluoroscopic results. AB - Firstly, the way of implementing approximatively the initial rollback of the natural tibiofemoral joint (TFJ) in a total knee replacement (AEQUOS G1 TKR) is discussed. By configuration of the curvatures of the medial and lateral articulating surfaces a cam gear mechanism with positive drive can be installed, which works under force closure of the femoral and tibial surfaces. Briefly the geometric design features in flexion/extension are described and construction conditioned kinematical and functional properties that arise are discussed. Due to a positive drive of the cam gear under the force closure during the stance phase of gait the articulating surfaces predominantly roll. As a result of rolling, a sliding friction is avoided, thus the resistance to motion is reduced during the stance phase. Secondly, in vivo fluoroscopic measurements of the patella tendon angle during flexion/extension are presented. The patella tendon angle/ knee flexion angle characteristic and the kinematic profile in trend were similar to those observed in the native knee during gait (0 degrees -60 degrees ). PMID- 22098090 TI - Effect of daily consumption of probiotic yoghurt on lipid profiles in pregnant women: a randomized controlled clinical trial. AB - BACKGROUND: Due to enhanced fat storage primarily during the mid-pregnancy period, pregnancy is associated with elevated levels of lipid profiles. To our knowledge, no reports are available indicating the effects of probiotic yoghurt consumption on serum lipid profiles in pregnant women. OBJECTIVE: This study was designed to determine the effects of daily consumption of probiotic yoghurt on lipid profiles of Iranian pregnant women. METHODS: This randomized single-blinded controlled clinical trial was performed among 70 pregnant women, primigravida, aged 18-30 years old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to consume 200 g/d of conventional (n=33) or the probiotic group (n=37) for 9 weeks. The probiotic yoghurt was a commercially available product prepared with the starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus, enriched with probiotic culture of two strains of lactobacilli (Lactobacillus acidophilus LA5) and bifidobacteria (Bifidobacterium animalis BB12) with a total of min 1 * 10(7) colony-forming units. The conventional yoghurt contained the starter cultures of S. thermophilus and L. bulgaricus. Fasting blood samples were taken at baseline and after 9-weeks intervention to measure serum lipid profiles. RESULTS: Although consumption of probiotic yogurt for 9 weeks had been resulted in a significant reduction in serum total- (-53.7 mg/dL, p=0.001), LDL- (-35.2 mg/dL, p=0.006) and HDL-cholesterol levels (-9.8 mg/dL, p=0.002) as well as serum triglyceride concentrations (-42.8 mg/dL, p=0.029), no significant differences were found comparing probiotic and conventional yogurts in terms of their effect on serum lipid profiles. Within-Group differences in conventional yogurt group revealed a significant reduction in HDL-cholesterol levels (-8.4 mg/dL, p=0.005) and borderline significant reduction in serum total cholesterol concentrations (-21.6 mg/dL, p=0.08). CONCLUSION: In conclusion, consumption of probiotic yogurt among pregnant women could not affect serum lipid profiles as compared to the conventional yogurt. PMID- 22098091 TI - A scoping review and research synthesis on financing and regulating oral care in long-term care facilities. AB - BACKGROUND: Oral health care for frail elders is grossly inadequate almost everywhere, and our knowledge of regulating and financing oral care in this context is unclear. OBJECTIVE: This scoping study examined and summarised the published literature available and the gaps in knowledge about regulating and financing oral care in long-term care (LTC) facilities. METHODS: We limited the electronic search to reports on regulating and financing oral care, including reports, commentaries, reviews and policy statements on financing and regulating oral health-related services. RESULTS: The broad electronic search identified 1168 citations, which produced 42 references, including 26 pieces of grey literature for a total of 68 papers. Specific information was found on public and private funding of care and on difficulties regulating care because of professional segregation, difficulties assessing need for care, uncertainty on appropriateness of treatments and issues around scope of professional practice. A wide range of information along with 19 implications and 18 specific gaps in knowledge emerged relevant to financing and regulating oral healthcare services in LTC facilities. CONCLUSIONS: Effort has been given to enhancing oral care for frail elders, but there is little agreement on how the care should be regulated or financed within the LTC sector. PMID- 22098092 TI - Rendering clinical psychology an evidence-based scientific discipline: a case study. AB - RATIONALE, AIMS AND OBJECTIVES: Both modern neuroscience and clinical psychology taken as separate fields have failed to reveal the explanatory mechanisms underlying mental disorders. The evidence acquired inside the mono-disciplinary matrices of neurobiology, clinical psychology and psychopathology are deeply insufficient in terms of their validity, reliability and utility. Further, no effective trans-disciplinary connections have been developed between them. ARGUMENT: In this context, our case study aims at illustrating some specific facets of clinical psychology as a crucial discipline for explaining and understanding mental disorder. The methods employed in clinical psychology are scrutinized using the exemplar case of the Minnesota Multiphasic Personality Inventory (MMPI). We demonstrate that a clinical interview and a clinical psychological rating scale consist of the same kind of cognitive content. The provisional difference can be described in terms of its having two comparable complementary cognitive structures. The test is composed of self-evaluation reports (items) formulated as questions or statements. The psychopathological structured interview is formulated in terms of subjective experience indicated as symptoms (these are self-reports recorded by the physician), complemented with the so-called 'signs' or the presumably 'objective' observations of the overt behaviours of the patient. However, the cognitive content of clinical judgment is beyond any doubt as subjective as the narrative of the patient. None of the components of the structured psychopathological interview is independent of the inter-subjective system created in the situation of clinical assessment. CONCLUSION: Therefore, the protocols from various clinicians that serve to sustain the reliability claim of the 'scientific' Diagnostic Statistical Manual of Mental Disorders cannot be regarded as independent measurements of the cognitive content and value of the psychological rating scales or vice versa. PMID- 22098094 TI - Insight into fractal self-assembly of poly(diallyldimethylammonium chloride)/sodium carboxymethyl cellulose polyelectrolyte complex nanoparticles. AB - Poly(diallyldimethylammonium chloride)-sodium carboxymethyl cellulose polyelectrolyte complexes (PDDA-CMCNa PECs) solids were prepared and dispersed in NaOH aqueous solution. Self-assembly of PECs nanoparticles during the solvent evaporation was examined by field emission electron microscopy (FESEM), atomic force microscopy (AFM), and fractal dimension analysis. It was found that tree shaped fractal patterns formed after the solvent (water) was dried at ambient temperatures, and the fractal pattern is composed of needle-shaped PEC aggregate (PECA) nanoparticles. Time-dependent FESEM observation revealed that the fractal pattern started with the formation of initial nucleon and it is growing, during which the diffusion limited aggregation (DLA) mechanism revealed and made the pattern branched. Physical insight into the DLA mechanism was discussed in detail. Effects of PEC concentrations, PEC compositions, solvent evaporation temperatures, pH of PEC dispersion, and chemical structures of PECs on the formation of self-assembled fractal pattern were studied. Generally, it was found that the morphologies, charge characters of PEC particles, and the solvent evaporation conditions play important roles during the fractal self-assembly process. PMID- 22098095 TI - Clinical signs and left atrial size in cats with cardiovascular disease in general practice. AB - OBJECTIVES: To evaluate population characteristics, clinical signs and simple echocardiographic measurements of a general practice population of cats, in identifying characteristics that reliably distinguish cats with heart disease from others, including those with respiratory disease, using widely available techniques. METHODS: Cats presented with heart disease (n=103), respiratory disease (n=19) and a normal group (n=29) were prospectively recruited. All cats were subject to full clinical examination, echocardiography and additional diagnostic procedures as appropriate to establish definitive diagnosis. Cats were classified as Group 1: no heart disease +/- respiratory disease; Group 2: heart disease with no clinical signs; Group 3: heart disease with clinical signs. Murmur, gallop sound and arrhythmia prevalence and left atrial size were compared between the groups. RESULTS: Low heart rates prevailed in Group 3. Murmurs were prevalent in Group 2, but in Group 3 prevalence was significantly lower. Dyspnoea, gallop sounds, arrhythmias and left atrial diameter were significantly different between groups. CLINICAL SIGNIFICANCE: Heart rate is unreliable for diagnosing heart failure in cats. Absence of murmur is prevalent in cats with clinical signs of heart failure, but arrhythmia and gallop sounds are prevalent. Echocardiographic measurement of left atrial diameter >16.5 mm may distinguish heart failure from respiratory disease in general practice. PMID- 22098093 TI - Soil bacterial communities of a calcium-supplemented and a reference watershed at the Hubbard Brook Experimental Forest (HBEF), New Hampshire, USA. AB - Soil Ca depletion because of acidic deposition-related soil chemistry changes has led to the decline of forest productivity and carbon sequestration in the northeastern USA. In 1999, acidic watershed (WS) 1 at the Hubbard Brook Experimental Forest (HBEF), NH, USA was amended with Ca silicate to restore soil Ca pools. In 2006, soil samples were collected from the Ca-amended (WS1) and reference watershed (WS3) for comparison of bacterial community composition between the two watersheds. The sites were about 125 m apart and were known to have similar stream chemistry and tree populations before Ca amendment. Ca amended soil had higher Ca and P, and lower Al and acidity as compared with the reference soils. Analysis of bacterial populations by PhyloChip revealed that the bacterial community structure in the Ca-amended and the reference soils was significantly different and that the differences were more pronounced in the mineral soils. Overall, the relative abundance of 300 taxa was significantly affected. Numbers of detectable taxa in families such as Acidobacteriaceae, Comamonadaceae, and Pseudomonadaceae were lower in the Ca-amended soils, while Flavobacteriaceae and Geobacteraceae were higher. The other functionally important groups, e.g. ammonia-oxidizing Nitrosomonadaceae, had lower numbers of taxa in the Ca-amended organic soil but higher in the mineral soil. PMID- 22098096 TI - Risk factors for hepatitis C virus acquisition and predictors of persistence among Egyptian children. AB - BACKGROUND: Hepatitis C virus (HCV) has a lower prevalence in children and knowledge is limited regarding the natural outcome of HCV infection in children. AIM: To study the risk factors of HCV acquisition and predictors of persistence in Egyptian children. METHODS: Children, 1-9 years of age, were evaluated for acquisition of HCV (anti-HCV positive regardless of viraemia) and persistence of HCV (anti-HCV and HCV-RNA positive) at two paediatric hepatology clinics in Cairo at enrollment and at 3 monthly intervals. Spontaneous clearance of HCV was defined as >= two positive anti-HCV antibody tests with negative HCV-RNA at least 6 months apart. RESULTS: Over a 33-month-period a total of 226 children <9 years of age were screened for HCV antibodies. Of those, 146 (65%) were anti-HCV positive of which 87 (60%) were HCV-RNA positive. The HCV acquisition was more likely to occur in older children (P = 0.003) with comorbid conditions (P < 0.01) compared to anti-HCV negative children. In a multivariate logistic regression analysis, the highest risk factors for HCV acquisition were surgical interventions [odds ratio (OR): 4.7] and blood transfusions (OR: 2.3). The highest risk factor for HCV persistence was dental treatment (OR: 16.9) and male gender (OR: 7.5). HCV persistence was also strongly associated with elevated baseline alanine aminotransaminase (ALT) levels (OR: 4.9) and fluctuating aspartate aminotransferase (AST) levels (OR: 8.1). CONCLUSION: Although surgical interventions and blood transfusion are significant risk factors for HCV acquisition in Egyptian children, dental treatment remains the highest risk factor for HCV chronic persistence in children. PMID- 22098097 TI - Mortality and cancer risk related to primary sclerosing cholangitis in a Swedish population-based cohort. AB - BACKGROUND: Population-based studies on the epidemiology of primary sclerosing cholangitis (PSC) are sparse. AIMS: To investigate mortality and risk of cancer, and to identify risk factors for hepatobiliary cancer and the combined end-point liver related death or liver transplantation (OLT) in a population-based PSC cohort in Vastra Gotaland, Sweden. METHODS: Primary sclerosing cholangitis cases were identified in diagnostic registries. Case validation and follow up was provided through individual review of case files and linkage to the Swedish Cancer and Cause of Death registries. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) for cancer were calculated in relation to the background population. Cox's proportional hazards analysis was used to calculate crude and adjusted relative risks (RRs). RESULTS: A total of 199 PSC patients were identified between 1992 and 2005. SMR in the PSC cohort was 4.20 (95% confidence interval (CI), 3.01-5.69). SIR for hepatobiliary cancer, cholangiocarcinoma and colorectal cancer were 177 (110-271), 868 (505-1390) and 2.87 (0.33-10.4) respectively. Age (RR=1.25 (1.01-1.53) per decade), female gender (RR=2.01 (1.09-3.72)), cholangitis (RR=2.56 (1.20-5.64)) and bilirubin (RR=3.95 (1.96-10.75) highest vs lowest quartile) were associated with the risk of liver related death or OLT. Age was associated with the risk of hepatobiliary cancer (RR 1.40 (1.01-1.95) per decade). CONCLUSIONS: Primary sclerosing cholangitis was associated with a four-fold increase in mortality in this population-based study. In accordance with previous studies, the risk of hepatobiliary cancer was dramatically increased. However, the increased risk of colorectal cancer reported in previous studies could not be confirmed. PMID- 22098098 TI - Beneficial use of steroids in hereditary neuropathy with liability to pressure palsy. AB - Management of hereditary neuropathy with liability to pressure palsy (HNPP) is primarily conservative, aimed at preventing nerve injury by avoiding trauma or other potential aggravating factors. No pharmacological treatment is known to be beneficial. We describe two adolescents, one with HNPP (male; aged 15y) and another with a clinical picture suggestive of HNPP (genetically unconfirmed; female; aged 14y), who showed considerable improvement of their symptoms after receiving corticosteroid therapy. Both individuals were symptomatic for at least 5 months before the treatment. Following corticosteroids, both individuals demonstrated rapid improvement leading to near-complete recovery of muscle power. Clinical improvement after corticosteroid therapy has been reported in some individuals with other hereditary neuropathies. Our cases demonstrate that corticosteroid therapy may also be beneficial in individuals with HNPP who have a protracted or incomplete course of recovery. PMID- 22098099 TI - Future candidates for indications of Helicobacter pylori eradication: do the indications need to be revised? AB - Since the discovery of Helicobacter pylori in 1982, the development of several treatment guidelines has allowed a consensus on the indications for H. pylori eradication. Beyond these currently accepted indications, including various upper gastrointestinal disorders and extragastric diseases, a significant amount of new information regarding H. pylori eradication is emerging. Certain types of acute gastritis, such as nodular gastritis, hypertrophic gastritis, Menetrier's disease, hemorrhagic gastritis, and granulomatous gastritis are reversible after H. pylori eradication. Further, for chronic gastritis, closed-type atrophic gastritis and complete-type intestinal metaplasia appear to be more reversible after H. pylori eradication than open-type atrophic gastritis and incomplete-type intestinal metaplasia. Eradication can also be considered in subjects younger than 40 years who have a family history of gastric cancer and in subjects with long-term medications that might lead to bleeding (antiplatelet agents) or atrophy (proton pump inhibitors). Emerging evidence indicates that H. pylori eradication could be an effective treatment for some extragastric diseases that are unresponsive to conventional therapy. In such conditions, routine screening for eradication of H. pylori has not previously been recommended; a "test-and treat" approach is suggested in the aforementioned situations. Given that H. pylori eradication is effective when the gastritis is reversible, future indications should be expanded to include acute gastric lesions that show marked improvement upon H. pylori eradication rather than just focusing on chronic gastric lesions. Future indications for H. pylori eradication should focus more on reversible lesions before preneoplastic conditions develop. PMID- 22098100 TI - How is sesamin metabolised in the human liver to show its biological effects? AB - INTRODUCTION: Sesamin is a major lignan found in sesame and is known to have various biological effects. Some of these biological effects occur following its metabolic conversion to corresponding catechols and, therefore, the study of sesamin metabolism is quite important. There is currently a need to identify the enzymes responsible for metabolism of sesamin so that scientists will be more able to predict sesamin-drug interactions. AREAS COVERED: The authors reviewed all the published literature with a focus on papers that dealt with metabolism of sesamin by drug-metabolising enzymes in rat and/or human liver, such as cytochrome P450 and UDP-glucuronosyltransferase. The article also reviews papers that dealt with the inhibition of enzymes by sesamin including drug-metabolising enzymes and other physiologically important enzymes. Additionally, the authors discuss the species-based differences in the metabolism of sesamin between rats and humans. EXPERT OPINION: A remarkable species-based difference was found in sesamin metabolism between humans and other animals; thus, it is very important that precautions are taken when predicting the physiological effects in humans from animal data. A mechanism-based inhibition of human CYP2C9 by sesamin was recently discovered, suggesting that it is important to evaluate the interaction between sesamin and drugs that are mainly metabolised by CYP2C9. Furthermore, further analysis of sesamin and episesamin and their molecular mechanisms are needed to make better use of sesamin supplements. PMID- 22098101 TI - RNA mimicry, a decoy for regulatory proteins. AB - Small non-coding RNA molecules (sRNA) are key regulators participating in complex networks, which adapt metabolism in response to environmental changes. In this issue of Molecular Microbiology, and in a related paper in Proc. Natl. Acad. Sci. USA, Moreno et al. (2011) and Sonnleitner et al. (2009) report on novel sRNAs, which act as decoys to inhibit the activity of the master post-transcriptional regulatory protein Crc. Crc is a key protein involved in carbon catabolite repression that optimizes metabolism improving the adaptation of the bacteria to their diverse habitats. Crc is a novel RNA-binding protein that regulates translation of multiple target mRNAs. Two regulatory sRNAs in Pseudomonas putida mimic the natural mRNA targets of Crc and counteract the action of Crc by sequestrating the protein when catabolite repression is absent. Crc trapping by a sRNA is a mechanism reminiscent to the regulation of the repressor of secondary metabolites (RsmA) in Pseudomonas, and highlights the suitability of RNA dependent regulation to rapidly adjust cell growth in response to environmental changes. PMID- 22098102 TI - Primary cutaneous Ewing sarcoma: a systematic review focused on treatment and outcome. AB - BACKGROUND: Despite intensive treatment, the overall prognosis of Ewing sarcoma of the bone remains poor. Primary cutaneous Ewing sarcoma very rarely occurs and the prognosis has been reported to be better in some small series. All cases of Ewing sarcoma are currently treated in the same way, regardless of their location. OBJECTIVES: To determine whether Ewing sarcoma of the bone and primary cutaneous Ewing sarcoma are different in terms of epidemiology and prognosis. METHODS: A systematic review of the literature was carried out using the keywords 'cutaneous Ewing's sarcoma', 'primary Ewing's sarcoma of skin' and 'primary neuroectodermal tumour and skin' in the Medline database. Series of five or more cases were included. RESULTS: Six series met the inclusion criteria, making a total of 61 patients. Median age at diagnosis was 17 years and 33% were male. The median size of the tumour was 2.3 cm. The treatment consisted of surgery in all cases, adjuvant multiagent chemotherapy in 69% of cases, adjuvant chemoradiotherapy in 38% of cases and adjuvant radiotherapy without adjuvant chemotherapy in 3% of cases. Six patients developed metastases, four of whom died. The overall survival was 93% and the 10-year probability of survival was estimated at 91% (95% confidence interval 83-100). CONCLUSION: This systematic review demonstrated epidemiological and prognostic differences between Ewing sarcoma of the bone and primary cutaneous Ewing sarcoma. Primary cutaneous Ewing sarcoma has a female predominance, occurs at a later age, but, more importantly, has a better outcome. Multimodal therapy for Ewing sarcoma is associated with immediate and long-term morbidity and mortality. Although the size of our study does not allow a definitive conclusion about treatment modalities, we suggest that a less toxic approach compared with conventional treatment should be investigated in primary cutaneous Ewing sarcoma. PMID- 22098103 TI - Comparison of clinical characteristics and management of inflammatory bowel disease in Hong Kong versus Melbourne. AB - BACKGROUND AND AIM: Inflammatory bowel disease (IBD), common in Melbourne, was rare but is now increasing in incidence in Hong Kong (HK). To investigate whether these are the same diseases in the West and East, potential causes of changing incidence, and to plan resource needs, an appreciation of clinical characteristics in contrasting populations is essential. METHODS: Disease characteristics were collected from prospectively populated IBD databases in two specialist centers in Melbourne, Australia and HK. RESULTS: Of 795 patients (Crohn's disease [CD] : ulcerative colitis [UC] Melbourne 272:159 and HK 161:203), the age of diagnosis was higher, there were proportionally more male patients with CD but no UC sex difference, fewer patients were current or ex smokers (CD 8% vs 50%; UC 17% vs 35%) and a family history of IBD was less common (2% vs 11%; P < 0.001) in HK compared to Melbourne. Stricturing and perianal CD were more common in HK (12% vs 6%; P < 0.001; and 29% vs 16%; P = 0.001, respectively). In HK for UC, more patients had extensive disease at diagnosis (42% vs 22%) but colectomy was less common (7% vs 20%; P < 0.001). In Melbourne there was greater steroid use at diagnosis and patients were more likely to receive an immunomodulator or anti-tumor necrosis factor agent. CONCLUSIONS: IBD in HK was diagnosed at an older age, and had more complicated disease behavior than in Melbourne. Medical therapy, however, was less intense in HK. These differences may relate to real differences in disease or delayed diagnosis due to late presentation and less disease recognition in HK. PMID- 22098104 TI - Clinicopathological and prognostic role of cyclin D1 in esophageal squamous cell carcinoma: a meta-analysis. AB - Cyclin D1 is one of the most commonly over-expressed oncogenes; however, its role in esophageal squamous cell carcinoma (ESCC) remains controversial. We conducted a meta-analysis of 20 studies, comprising 2,041 patients to clarify this issue. In all studies, paraffin-embedded surgical specimens were collected and the status of cyclin D1 was determined by immunohistochemistry (IHC). The combined odds ratios (Ors) for cyclin D1 expression were 0.74 (95% confidence interval [CI]: 0.58-0.93) for well and moderately differentiated versus poorly differentiated tumors, 0.65 (95% CI: 0.45-0.94) for T1/T2 versus T3/ T4 tumors, 0.59 (95% CI: 0.39-0.90) for N0 versus N1 tumors, and 0.48 (95% CI: 0.33-0.71) for stage I/II versus stage III/IV diseases, respectively. The association between cyclin D1 expression and prognosis was examined in 10 studies, and the combined hazard ratio was 1.78 (95% CI: 1.49-2.12). Cyclin D1 expression level detected by IHC is associated with worst clinicopathological features and prognosis for ESCC. PMID- 22098105 TI - Tissue imaging using nanospray desorption electrospray ionization mass spectrometry. AB - Ambient ionization imaging mass spectrometry is uniquely suited for detailed spatially resolved chemical characterization of biological samples in their native environment. However, the spatial resolution attainable using existing approaches is limited by the ion transfer efficiency from the ionization region into the mass spectrometer. Here, we present a first study of ambient imaging of biological samples using nanospray desorption ionization (nano-DESI). Nano-DESI is a new ambient pressure ionization technique that uses minute amounts of solvent confined between two capillaries comprising the nano-DESI probe and the solid analyte for controlled desorption of molecules present on the substrate followed by ionization through self-aspirating nanospray. We demonstrate highly sensitive spatially resolved analysis of tissue samples without sample preparation. Our first proof-of-principle experiments indicate the potential of nano-DESI for ambient imaging with a spatial resolution of better than 12 MUm. The significant improvement of the spatial resolution offered by nano-DESI imaging combined with high detection efficiency will enable new imaging mass spectrometry applications in clinical diagnostics, drug discovery, molecular biology, and biochemistry. PMID- 22098106 TI - Parallel allochronic divergence in a winter moth due to disruption of reproductive period by winter harshness. AB - The disruption of reproductive timing by climatic harshness may result in the temporal isolation of conspecific populations and, ultimately, in speciation. However, whether temporal isolation alone can act as the force initiating speciation and how often the same type of climatic disruption results in the divergence of allochronic populations in a lineage are largely unknown. The reproductive period of the winter geometrid moth Inurois punctigera is separated into early and late winter in habitats with severe winters, but not in habitats with mild winters, suggesting that the reproductive season is disrupted by the harshness of the mid-winter period. Here, we show that sympatric pairs of early- and late-winter populations that differ in origin exist in different regions, suggesting a parallel divergence of reproductive timing. In each region, significant genetic differentiation exists between these early- and late-winter populations, suggesting that the temporal reproductive isolation has persisted. Moreover, we demonstrate that the temporal isolation, in comparison with geographic isolation, contributes greatly to the genetic differentiation among geographic and temporal populations by an analysis of molecular variance and by a comparison of genetic differentiations (F(ST) ) between geographic populations with and without difference in reproductive season. Our results suggest that adaptive divergence of allochronically reproducing populations has occurred independently in different regions, implying the generality of the role of temporal isolation in initiating speciation in a winter moth lineage. PMID- 22098107 TI - 'Real-time' PCR-based detection of Coxiella burnetii using conventional techniques. AB - The diagnosis of Q fever (Coxiella burnetii infection) relies primarily on the serological detection of specific antibodies. Recently, PCR-based methods have been introduced in diagnostic laboratories. Unfortunately, the fastest and most reliable 'real-time' detection method, which employs the 'online' detection of target nucleotide sequences while the amplification process is still in progress, requires expensive devices and consumables. In this study, we present a simple method that combines the simplicity of conventional PCR with new technical and methodical enhancements, resulting in a fast, specific and easy method for the molecular detection of C. burnetii. A collection of C. burnetii reference strains was tested with the modified conventional gel-based PCR approach applying a particluar PCR buffer (QIAGEN((r)) Fast Cycling PCR kit) and using a closed ready to-use gel-cassette-system (FlashGel((r))) for the visualization of specific PCR products. The modified conventional PCR method reached nearly the speed of the LightCycler((r)) HybProbe real-time PCR assay (120 vs. 90 min) and showed equal sensitivity and specificity. The general cost per PCR run was 25% less than that for the LightCycler method. These improvements make this method suitable for small laboratories with limited resources and for deployable PCR diagnostics in field laboratories. PMID- 22098108 TI - Inhibition of IGF-1 signaling by genistein: modulation of E-cadherin expression and downregulation of beta-catenin signaling in hormone refractory PC-3 prostate cancer cells. AB - Elevated levels of insulin-like growth factor-1 (IGF-1) are associated with an increased risk of several different cancers, including prostate cancer. Inhibition of IGF-1 and the downstream signaling pathways mediated by the activation of the IGF-1 receptor (IGF-1R) may be involved in inhibiting prostate carcinogenesis. We investigated whether genistein downregulated the IGF-1/IGF-1R signaling pathway and inhibited cell growth in hormone refractory PC-3 prostate cancer cells. Genistein treatment caused a significant inhibition of IGF-1 stimulated cell growth. Flow cytometry analysis revealed that genistein significantly decreased the number of IGF-1-stimulated cells in the G0/G1 phase of the cell cycle. In IGF-1-treated cells, genistein effectively inhibited the phosphorylation of IGF-1R and the phosphorylation of its downstream targets, such as Src, Akt, and glycogen synthase kinase-3beta (GSk-3beta). IGF-1 treatment decreased the levels of E-cadherin but increased the levels of beta-catenin and cyclin D1. However, genistein treatment greatly attenuated IGF-1-induced beta catenin signaling that correlated with increasing the levels of E-cadherin and decreasing cyclin D1 levels in PC-3 cells. In addition, genistein inhibited T cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity. These results showed that genistein effectively inhibited cell growth in IGF-1-stimulated PC-3 cells, possibly by inhibiting downstream of IGF-1R activation. PMID- 22098109 TI - Asymmetric hydrogenation of heteroarenes and arenes. PMID- 22098110 TI - The effect of erythropoietin on platelet and endothelial activation markers: a prospective trial in healthy volunteers. AB - Erythropoietin (EPO) enhances formation of red blood cells and also affects thrombopoiesis and platelet function. We hypothesized that the effect of EPO may be reflected by changes in thromboxane B2 (TXB2) and endothelial cell function. Six male and six female subjects received recombinant human epoetin alpha (Erypo(r)) intravenously (300 U/kg). Biomarker levels were assessed at baseline and 4, 24, 48 and 72 hours after infusion. Epoetin alpha increased TXB2 levels by 140%, which reached significance at 48 hours (6.6 +/- 5 ng/ml vs. 15 +/- 9 ng/ml; p = 0.044) and remained at that level at 72 hours. In line, epoetin alpha increased E-selectin levels by 25% already at 24 hours (39 +/- 21 ng/ml vs. 49 +/ 26 ng/ml; p < 0.001) which stayed at this level until 72 hours (p < 0.001). The raise in platelet activation markers corresponded to an 88% increase in reticulocyte count (43 +/- 10 * 10(9)/l vs. 81 +/- 17 * 10(9)/l; p < 0.001) and a 9% increase in platelet count at 72 hours (224 +/- 45 * 10(9)/l vs. 244 +/- 52 * 10(9)/l; p = 0.005). Thrombomodulin and von Willebrand factor concentrations were not significantly altered by epoetin alpha. Interestingly, gender differences in the baseline levels of E-selectin and thrombomodulin were observed. E-selectin and thrombomodulin levels were doubled in men compared to women (51 +/- 24 and 28 +/- 10 ng/ml; p = 0.025 and 30 +/- 5 ng/ml vs. 16 +/- 5 ng/ml; p = 0.002, respectively). EPO increases TXB2 serum levels and soluble E-selectin. Further studies are needed to investigate whether these markers might be useful for estimation of thromboembolic risk during EPO-therapy and whether inhibition of thromboxane formation may lower thrombotic complications during EPO treatment: NCT01392612. PMID- 22098111 TI - Systematic knockdown of morphine pathway enzymes in opium poppy using virus induced gene silencing. AB - Opium poppy (Papaver somniferum) remains the sole commercial source for several pharmaceutical alkaloids including the narcotic analgesics codeine and morphine, and the semi-synthetic drugs oxycodone, buprenorphine and naltrexone. Although most of the biosynthetic genes have been identified, the post-transcriptional regulation of the morphinan alkaloid pathway has not been determined. We have used virus-induced gene silencing (VIGS) as a functional genomics tool to investigate the regulation of morphine biosynthesis via a systematic reduction in enzyme levels responsible for the final six steps in the pathway. Specific gene silencing was confirmed at the transcript level by real-time quantitative PCR (polymerase chain reaction), and at the protein level by immunoblot analysis using antibodies raised against salutaridine synthase (SalSyn), salutaridine reductase (SalR), salutaridine 7-O-acetyltransferase (SalAT), thebaine 6-O demethylase (T6ODM), codeinone reductase (COR), and codeine O-demethylase (CODM). In some cases, silencing a specific biosynthetic gene resulted in a predictable accumulation of the substrate for the corresponding enzyme. Reduced SalSyn, SalR, T6ODM and CODM protein levels correlated with lower morphine levels and a substantial increase in the accumulation of reticuline, salutaridine, thebaine and codeine, respectively. In contrast, the silencing of genes encoding SalAT and COR resulted in the accumulation of salutaridine and reticuline, respectively, which are not the corresponding enzymatic substrates. The silencing of alkaloid biosynthetic genes using VIGS confirms the physiological function of enzymes previously characterized in vitro, provides insight into the biochemical regulation of morphine biosynthesis, and demonstrates the immense potential for metabolic engineering in opium poppy. PMID- 22098112 TI - Oxypurinol, allopurinol and allopurinol-1-riboside in plasma following an acute overdose of allopurinol in a patient with advanced chronic kidney disease. PMID- 22098113 TI - Comparison of combinatorial clustering methods on pharmacological data sets represented by machine learning-selected real molecular descriptors. AB - Cluster algorithms play an important role in diversity related tasks of modern chemoinformatics, with the widest applications being in pharmaceutical industry drug discovery programs. The performance of these grouping strategies depends on various factors such as molecular representation, mathematical method, algorithmical technique, and statistical distribution of data. For this reason, introduction and comparison of new methods are necessary in order to find the model that best fits the problem at hand. Earlier comparative studies report on Ward's algorithm using fingerprints for molecular description as generally superior in this field. However, problems still remain, i.e., other types of numerical descriptions have been little exploited, current descriptors selection strategy is trial and error-driven, and no previous comparative studies considering a broader domain of the combinatorial methods in grouping chemoinformatic data sets have been conducted. In this work, a comparison between combinatorial methods is performed,with five of them being novel in cheminformatics. The experiments are carried out using eight data sets that are well established and validated in the medical chemistry literature. Each drug data set was represented by real molecular descriptors selected by machine learning techniques, which are consistent with the neighborhood principle. Statistical analysis of the results demonstrates that pharmacological activities of the eight data sets can be modeled with a few of families with 2D and 3D molecular descriptors, avoiding classification problems associated with the presence of nonrelevant features. Three out of five of the proposed cluster algorithms show superior performance over most classical algorithms and are similar (or slightly superior in the most optimistic sense) to Ward's algorithm. The usefulness of these algorithms is also assessed in a comparative experiment to potent QSAR and machine learning classifiers, where they perform similarly in some cases. PMID- 22098114 TI - Trends in maternal mortality over 29 years in a Kuwait Tertiary Teaching Hospital: signs of progress? AB - This study aims at (1) Assessing trends in maternal mortality in kuwait (2) Define strategies for prevention. METHODS: Retrospective analysis of maternal deaths that occurred among, 55,979 live births at a tertiary hospital, between 1980 and 2009. RESULTS: There were 14 maternal deaths, and 55,979 live births, giving a maternal mortality rate of 25 per 100,000 live birth. In terms of decades maternal mortality declined from 54.8 in 1980-90 to 28.4 in 1990-2000 and continued to decline to 12.2 in 2000-2009. Thromboembolism (28.6%), Obstetric haemorrhage (21.5%) and Eclampsia (14.3%) were the leading causes of direct deaths. Cardiac disease is the most common cause of indirect deaths (14.3%) followed by H1N1 pneumonia 7.1%. Eclampsia contributed to 40% of deaths, only in the 1980s. Thromboembolism caused 28.6% of deaths, 50% of which were in the last 9 years. Indirect deaths from cardiomyopathies (66.7%) gained prominence in the 1990s. No deaths from puerperal sepsis were reported after the 1980s (14.3%). CONCLUSIONS: Maternal mortality rates are decreasing significantly (p<0.01) at our institution over the last 29 years. Obstetric haemorrhage and thromboembolism remain important causes of maternal mortality. Substandard care was identified in 70% of Direct and 55% of indirect deaths. PMID- 22098115 TI - Systematic review and meta-analysis of bifrontal electroconvulsive therapy versus bilateral and unilateral electroconvulsive therapy in depression. AB - OBJECTIVES: Our aim was to perform a meta-analysis of randomized controlled trials comparing efficacy and side effects of bifrontal (BF) ECT to bitemporal (BT) or unilateral (RUL) ECT in depression. METHODS: We performed a systematic review of randomized controlled trials comparing BF ECT with RUL or BT ECT in depression. Eight trials (n=617) reported some cognitive outcome. Efficacy was measured by reduction in Hamilton Depression Rating Scale score. Cognitive outcomes were limited to Mini-Mental State Examination (MMSE) in seven studies, with two studies measuring each of: Complex-figure delayed recall, Trail-making tests and verbal learning. RESULTS: Efficacy was equal between BF and BT ECT (Hedges's g=0.102, P=0.345, confidence interval (CI): -0.110, 0.313) and BF and RUL ECT (standardized mean difference=-0.12, P=0.365, CI: -0.378, 0.139). Post treatment MMSE score decline was less for BF than BT ECT (g=0.89, CI: 0.054, 1.724) but not RUL ECT. RUL ECT impaired Complex figure recall more than BF ECT (g=0.76, CI :0.487, 1.035), but BF ECT impaired word recall more than RUL ECT (g= 1.45, CI: -2.75, -0.15). CONCLUSIONS: Bifrontal ECT is not more effective than BT or RUL ECT but may have modest short-term benefits for specific memory domains. BF ECT has potential advantages, but given longer experience with BT and RUL, bifrontal ECT requires better characterization. PMID- 22098116 TI - Treatment of extrahepatic congenital portosystemic shunts in dogs - what is the evidence base? AB - A variety of surgical treatments and medical therapies are recommended for dogs with extrahepatic congenital portosystemic shunts (CPSS). The objective of this review was to assess the evidence base for the management of extrahepatic CPSS in dogs. An online bibliographic search was performed in November 2010 to identify articles relating to the question "Which of the treatment options for extrahepatic CPSS in dogs offers the best short- and long-term outcomes?" Articles were assigned a level of evidence based on a modified grading system. Thirty-eight articles were included in the review. Thirty-six articles were classified as grade 4 and two as grade 5. The timings and methods of assessment of short- and long-term outcomes varied widely between studies. One prospective study (grade 4a) showed that surgically treated dogs survived significantly longer than medically treated dogs. Four retrospective studies (grade 4b) compared the outcome of two surgical techniques but there were no statistically significant differences between treatment groups in terms of complications or outcome. The review found that the evidence base for the treatment of extrahepatic CPSS is weak. There is a lack of evidence of short- and long-term outcomes to recommend one treatment over another. PMID- 22098117 TI - Effect of toothbrushing, chemical disinfection and thermocycling procedures on the surface microroughness of denture base acrylic resins. AB - OBJECTIVE: This study verified the surface microroughness of denture acrylic resins submitted to toothbrushing, chemical disinfection and thermocycling procedures. MATERIAL AND METHODS: Samples were prepared according to conventional, microwaved and boiled resins and submitted to microroughness measurements before and after procedures using a profilometer (Ra). Data were subjected to anova and Tukey's test (5%). RESULTS: Before thermocycling, a difference was found among treatments for microwaved and boiled resins, with greater values for toothbrushing and lower values for Efferdent and hypochlorite; control was intermediate. Differences among resins were observed for treatments, with higher values for boiled resin and lower values for conventional and microwaved resins. After thermocycling, differences were found for microwaved resin, with a higher value for toothbrushing and a lower value for Efferdent and hypochlorite; control was intermediate. Tooth-brushed boiled resin presented higher values and hypochlorite lower values; control and Efferdent were intermediates. Differences among resins were seen for treatments, with higher values for boiled resin and lower values for conventional and microwaved resins. Boiled resin presented differences for toothbrushing and hypochlorite, before and after thermocycling procedures were compared. CONCLUSIONS: For microwaved and boiled resins, toothbrushing and chemical disinfection promoted different levels of surface microroughness when associated or not with thermocycling. PMID- 22098118 TI - Pump-dump-probe and pump-repump-probe ultrafast spectroscopy resolves cross section of an early ground state intermediate and stimulated emission in the photoreactions of the Pr ground state of the cyanobacterial phytochrome Cph1. AB - The primary photoreactions of the red absorbing ground state (Pr) of the cyanobacterial phytochrome Cph1 from Synechocystis PCC 6803 involve C15?C16 Z-E photoisomerization of its phycocyanobilin chromophore. The first observable product intermediate in pump-probe measurements of the photocycle, "Lumi-R", is formed with picosecond kinetics and involves excited state decay reactions that have 3 and 14 ps time constants. Here, we have studied the photochemical formation of the Lumi-R intermediate using multipulse picosecond visible spectroscopy. Pump-dump-probe (PDP) and pump-repump-probe (PRP) experiments were carried out by employing two femtosecond visible pulses with 1, 14, and 160 ps delays, together with a broadband dispersive visible probe. The time delays between the two excitation pulses have been selected to allow interaction with the dominant (3 and 14 ps) kinetic phases of Lumi-R formation. The frequency dependence of the PDP and PRP amplitudes was investigated at 620, 640, 660, and 680 nm, covering excited state absorption (lambda(max) = 620 nm), ground state absorption (lambda(max) = 660 nm), and stimulated emission (lambda(max) = 680 nm) cross sections. Experimental double difference transient absorbance signals (DeltaDeltaOD), from the PDP and PRP measurements, required corrections to remove contributions from ground state repumping. The sensitivity of the resulting DeltaDeltaOD signals was systematically investigated for possible connectivity schemes and photochemical parameters. When applying a homogeneous (sequentially decaying) connectivity scheme in both the 3 and 14 ps kinetic phases, evidence for repumping of an intermediate that has an electronic ground state configuration (GSI) is taken from the dump-induced S1 formation with 620, 640, and 660 nm wavelengths and 1 and 14 ps repump delays. Evidence for repumping a GSI is also seen, for the same excitation wavelengths, when imposing a target connectivity scheme proposed in the literature for the 1 ps repump delay. In contrast, using a 680 nm dump pulse, ground state formation is observed for all models examined. The DeltaDeltaOD signals were dominated by stimulated emission, at both 1 and 14 ps delays for the longer wavelength excitation. The GSI, which is revealed by the PRP measurements and not resolved from pump-probe measurements, is found to be directly formed from the excited state of Pr, and its formation is considered using heterogeneous, homogeneous, and target models to globally fit the data. PMID- 22098119 TI - Pretransplant severe hepatic encephalopathy, peritransplant sodium and post-liver transplantation morbidity and mortality. AB - BACKGROUND: Hepatic encephalopathy (HE) does not enhance the prediction of model of end-stage liver disease (MELD) wait-list mortality, but its influence on post liver transplantation (LT) morbidity and mortality is largely unknown. AIMS: To examine the association between severe pre-LT HE and peri-LT serum sodium levels as well as post-LT length of stay (LOS) and survival. METHODS: A retrospective cohort of 393 adult patients undergoing first LT for end-stage liver disease and followed for a median of 4 years post-LT was performed to evaluate the association between severe HE within the 30 days prior to LT and selected in hospital post-LT outcomes. RESULTS: Thirty-nine (10%) of the cohort had severe HE pre-LT. Patients with severe HE more frequently had Na changes of >=15 mmol/L in the peri-LT period (P = 0.002). LOS was significantly longer for severe HE than non-severe HE patients (16 vs. 8 days, P < 0.0001) and this association was independent of MELD, presence of hepatocellular carcinoma, pre-LT nadir serum sodium and pre- to post-LT change in serum sodium. The 1-year mortality was 15% in the severe HE vs. 7% in the non-severe HE groups (HR = 2.19, P = 0.08), and this difference was attenuated by adjusting for pre-LT severe hypernatremia, but increased by adjusting for donor risk index. CONCLUSION: Severe HE mainly affects LOS, and this association is independent of MELD. Whether the large changes in peri-LT serum Na, more frequently seen in the severe HE group, contribute to post LT morbidity requires further study. PMID- 22098120 TI - Synthesis of (+)-phenserine using an interrupted Fischer indolization reaction. AB - A concise synthesis of the Alzheimer's therapeutic (+)-phenserine is described. The approach features an interrupted Fischer indolization to construct the pyrrolidinoindoline core, in addition to a classical resolution to arrive at phenserine in enantioenriched form. PMID- 22098121 TI - "Normal" liver stiffness values differ between men and women: a prospective study for healthy living liver and kidney donors in a native Korean population. AB - BACKGROUND AND AIM: Liver stiffness (LS) measurement can distinguish individuals with potential liver disease (LD) from the general population. However, if LS is sex-sensitive, prevalence of LD may be incorrectly estimated when the same reference LS value is applied irrespective of sex. Here, we evaluated whether normal ranges of LS differ between healthy men and women. METHODS: LS was measured in a cohort of healthy living liver and kidney donors, none of whom suffered from diabetes mellitus, hypertension, hepatitis B or C virus infection, heart or liver dysfunction, or metabolic syndrome. Patients with abnormal laboratory findings related to potential LD (platelet count < 150 * 10(3) /uL; aspartate aminotransferase > 40 IU/L; alanine aminotransferase [ALT] > 40 IU/L; albumin < 3.3 g/dL; total bilirubin > 1.2 mg/dL; gamma-glutamyl transpeptidase > 54 IU/L; alkaline phosphatase > 115 IU/L) were excluded. RESULTS: Among 242 patients analyzed, the mean age was 34.1 for men (n = 121) and 40.5 years for women (n = 121) (P < 0.001). Men had a higher mean LS value than women (5.2 +/- 1.2 vs 4.8 +/- 1.1 kPa/P < 0.001). Multivariate-linear regression analysis identified sex as the only independent factor for LS values (beta = 0.361/P = 0.021). Using the 5th-95th percentiles, we determined normal LS ranges of 3.7-7.0 kPa in men and 3.3-6.8 kPa in women. In subgroups with ALT < 30 IU/L (subgroup-1, n = 216) and ALT < 20 IU/L (subgroup-2, n = 163), men had significantly higher LS values than women (5.2 +/- 1.3 vs 4.7 +/- 1.1 kPa/P = 0.003 and 5.1 +/- 1.2 vs 4.7 +/- 1.1 kPa/P = 0.030, respectively), demonstrating an independent sex effect (beta = 0.483/P = 0.003 and beta = 0.389/P = 0.030, respectively). CONCLUSIONS: An independent sex effect on LS values was confirmed. Thus, sex-specific references should be used for effective screening based on LS measurements. PMID- 22098123 TI - Dermatological phenotype in Costello syndrome: consequences of Ras dysregulation in development. AB - BACKGROUND: The RASopathies are a class of human genetic syndromes caused by germline mutations in genes that encode protein components of the Ras/mitogen activated protein kinase (MAPK) pathway. Costello syndrome (CS) is a RASopathy caused by mutations in the HRAS gene, a key regulator of signal transduction. OBJECTIVE: To quantify the specific cutaneous phenotype observed in 46 individuals with Costello syndrome with confirmed HRAS mutations. METHODS: This was a cross-sectional study. Dermatological surveys were designed by the authors and were completed by parents of mutation-positive individuals with CS at the Costello Syndrome Family Network (CSFN) conferences in 2007 and 2009. Dermatological examinations were performed by the authors at the CSFN conferences. RESULTS: Cutaneous papillomas were reported in 33 of the 46 (72%) participants, with age of onset ranging from infancy to 22years. Individuals with CS are more likely than patients with cardiofaciocutaneous syndrome (CFC) to present with cutaneous papillomas (72% vs. 5%, P<0.001) and palmoplantar keratoderma (76% vs. 36%, P<0.001). Individuals with CS are less likely than individuals with CFC to present with sparse or absent eyebrows (9% vs. 90%, P<0.001) or keratosis pilaris (33% vs. 80%, P=0.001). This study also identified that loose, redundant skin on the hands and feet, 'stippled' dermatoglyphs (pachydermatoglyphia) on the fingertips (eight of 26, 31%) and acanthosis nigricans (17 of 46, 37%) are frequent features of CS. CONCLUSIONS: While there is significant phenotypic overlap among syndromes of the Ras/MAPK pathway, individuals with CS are more likely than individuals with CFC syndrome to present with cutaneous papillomas, palmoplantar keratoderma and full eyebrows, and are less likely to present with ulerythema ophryogenes, keratosis pilaris or multiple naevi. The dermatological features of CS, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signalling in cutaneous paraneoplastic syndromes. PMID- 22098124 TI - The influence of knee marker placement error on evaluation of gait kinematic parameters. AB - Vicon motion system is an accurate equipment for objective gait analysis. According to clinical experience the most important source of errors in kinematics is marker misplacement. It seems that knee marker placement is especially important because of its direct influence on two body segments: thigh and shank. There is little data in the literature on how the misplacement of knee marker determines the changes of kinematic parameters. Therefore the aim of this study was to collect the kinematic data of subjects with different knee pathologies (one with knee flexion contracture, the second with knee hyperextension) while knee marker position was changed in a systematical way. They were walking with their natural, preferred speed. The data were collected using VICON460 motion system, the Helen Hayes marker set and Plug-In-Gait model. Then they were processed based on Polygon software. The results of both subjects showed the changes of kinematics, depending on the knee marker misplacement. The assessed joint ranges of angle change were: in knee, 18 degrees in sagittal plane and 20 degrees in frontal plane; in hip, 10 degrees in sagittal plane and 24 degrees in transversal plane; in ankle, 10 degrees in sagittal plane and 25 degrees in transversal plane. This paper presents the detailed data which could help the users of such systems to interpret the kinematic data. PMID- 22098126 TI - Bioactive actions of pomegranate fruit extracts on leukemia cell lines in vitro hold promise for new therapeutic agents for leukemia. AB - Studies suggest that pomegranates contain bioactive chemicals with potential for treatment and prevention of cancer. Pomegranate juice extracts (PJE) have been shown to inhibit cellular proliferation and tumor growth and induce cell death via apoptosis in a number of cancer cell lines. However, to date, few studies have investigated the potential of PJE in the treatment of leukemia. We investigated the potential effect of PJE on induction of apoptosis and inhibition of cellular proliferation in 8 leukemia cell lines (4 lymphoid and 4 myeloid) and nontumor hematopoietic stem cells (control cells). Apoptosis was assessed by 2 methods: Annexin V-FITC/propidium iodide staining with flow cytometric analysis and 4'-6-diamidino-2-phenylindole (DAPI) morphological assessment. Cell cycle stage was investigated using propidum iodide staining of DNA content and flow cytometric analysis. Live cell counts were also performed using a trypan exclusion assay. PJE significantly induced apoptosis in all cell lines, including nontumor control cells, although lymphoid cells and 2 of the myeloid cell lines were more sensitive. Furthermore, PJE induced cell cycle arrest. These results were confirmed by DAPI analysis and viable cell counts using trypan blue exclusion assay. Our results provide evidence that PJE contain bioactive compounds that could be used in the treatment of leukemia. PMID- 22098125 TI - Atypical timing and presentation of periventricular haemorrhagic infarction in preterm infants: the role of thrombophilia. AB - AIM: Periventricular haemorrhagic infarction (PVHI) is a complication of preterm birth associated with cardiorespiratory instability. To date, the role of thrombophilia as a possible additional risk factor in infants with atypical timing and presentation of PVHI has not been investigated. METHOD: This was a retrospective cohort study of preterm infants who developed PVHI with an atypical timing and presentation either of antenatal onset or late in the postnatal course in the absence of a preceding sudden deterioration of their clinical condition. In infants with atypical PVHI mutation analysis of the factor V Leiden (G1691A), prothrombin (G20210A) gene, and C677T and A1298C polymorphisms in the MTHFR gene was performed, and plasma lipoprotein(a) and homocysteine levels were measured. RESULTS: Sixty-two preterm infants who presented with a PVHI were studied. Seventeen had an atypical presentation (seven males, 10 females; median birthweight 1170g [range 580-1990g]; median gestational age 30.6wks [range 28.7 33.7wks]). The typical PVHI group comprised 28 males and 17 females (median birthweight 1200g [range 670-2210g]; median gestational age 29.6wks [range 25.3 33.6wks]). Among the 17 infants with atypical presentation, the factor V Leiden mutation was found in seven infants (41%) as well as in the mothers of six of these seven infants; in one infant this was concomitant with a prothrombin gene mutation. A polymorphism in the MTHFR gene was also present in these infants. In two infants with an atypical presentation who were tested for this, a mutation in the COL4A1 gene was found (reported previously). All but two of the infants with an atypical presentation developed spastic unilateral cerebral palsy. INTERPRETATION: An atypical presentation of PVHI in preterm infants tends to occur more often in the presence of thrombophilia. Testing of thrombophilia, especially factor V Leiden and prothrombin gene mutation, is recommended in these infants. PMID- 22098127 TI - Sustained attention to response task (SART) shows impaired vigilance in a spectrum of disorders of excessive daytime sleepiness. AB - The sustained attention to response task comprises withholding key presses to one in nine of 225 target stimuli; it proved to be a sensitive measure of vigilance in a small group of narcoleptics. We studied sustained attention to response task results in 96 patients from a tertiary narcolepsy referral centre. Diagnoses according to ICSD-2 criteria were narcolepsy with (n=42) and without cataplexy (n=5), idiopathic hypersomnia without long sleep time (n=37), and obstructive sleep apnoea syndrome (n=12). The sustained attention to response task was administered prior to each of five multiple sleep latency test sessions. Analysis concerned error rates, mean reaction time, reaction time variability and post error slowing, as well as the correlation of sustained attention to response task results with mean latency of the multiple sleep latency test and possible time of day influences. Median sustained attention to response task error scores ranged from 8.4 to 11.1, and mean reaction times from 332 to 366ms. Sustained attention to response task error score and mean reaction time did not differ significantly between patient groups. Sustained attention to response task error score did not correlate with multiple sleep latency test sleep latency. Reaction time was more variable as the error score was higher. Sustained attention to response task error score was highest for the first session. We conclude that a high sustained attention to response task error rate reflects vigilance impairment in excessive daytime sleepiness irrespective of its cause. The sustained attention to response task and the multiple sleep latency test reflect different aspects of sleep/wakefulness and are complementary. PMID- 22098128 TI - Global gene expression profiling of Ehrlichia ruminantium at different stages of development. AB - Ehrlichia ruminantium (ER), the causative agent of heartwater on ruminants, is an obligate intracellular bacterium transmitted by ticks of the genus Amblyomma. Previous studies have shown that early stages of development may be critical for Ehrlichia pathogenicity. To gain insights into the biology of intracellular ER, we determined the genome-wide transcriptional profile of ER replicating inside bovine aortic endothelial cells using DNA microarrays. At intermediate and late stages of infection (reticulate and elementary bodies, respectively), a total of 54 genes were differentially expressed. Among them, we measured by q-RTPCR the overexpression of 11 of 14 genes. A number of genes involved in metabolism, nutrient exchange, and defense mechanisms, including those involved in resistance to oxidative stress, were significantly induced in ER reticulate bodies. This is consistent with the oxidative stress condition and nutrient starvation that seem to occur in Ehrlichia-containing vacuoles. During the lysis stage of development, when ER is infectious, we showed the overexpression of a transcription factor, dksA, which is also known to induce virulence in other pathogens such as Salmonella typhimurium. Our results suggest a possible role of these genes in promoting ER development and pathogenicity. PMID- 22098129 TI - 50th anniversary of the discovery of ibuprofen: an interview with Dr Stewart Adams. AB - 2011 marks the 50th anniversary of the discovery of ibuprofen. This article is a focus on the personal reflections and career of Dr Stewart Adams OBE, the scientist whose research lead to the discovery of the cyclooxygenase inhibitor. When Dr Adams discovered ibuprofen, he was working as a pharmacologist in the Research Department for the Boots Pure Drug Company Ltd. Dr Adams was assigned to work on rheumatoid arthritis (RA) and chose in 1953 to search for a drug that would be effective in RA but would not be a corticosteroid. He was one of the first workers in this field that later became known as NSAIDs (Non-Steroidal Anti Inflammatory Drugs). In 1961, Dr Adams with John Nicholson, the organic chemist, filed a patent for the compound 2-(4-isobutylphenyl) propionic acid, later to become one of the most successful NSAIDs in the modern world, ibuprofen. In this article, Dr Adams gives his modest insight into the early stages and initial observations which led to this world-wide success. PMID- 22098130 TI - Drug-induced immune thrombocytopenia: a descriptive survey in the French PharmacoVigilance database. AB - The aim of this survey was to describe drug-induced immune thrombocytopenia (ITP) reported in the French PharmacoVigilance database (FPVD) and to discuss the drugs involved. The request to the FPVD used the seven most accurate diagnosis codes to identify ITP. The study was restricted to cases reported from 2007 to 2010 and at least "possible" according to the French causality assessment score. We then described the population's characteristics, the drugs involved, the clinical symptoms, and the course of ITP. For each drug, we estimated the causality assessment score developed by George for drug-induced ITP. We included 59 drug induced ITP. Among them, 45.8% were post-vaccinal: they mainly occurred in children (median age: 16 years). Main vaccines were diphtheria-tetanus poliomyelitis (DTP, 9 cases), influenza (n=8) and measles, mumps, and rubella (MMR, n=7). Regarding the 33 non-vaccinal cases: some drugs are well-known as triggering ITP (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), n=5; abciximab, n=4, acetaminophen, n=2). Other drugs inducing ITP were involved, like serotonin reuptake inhibitors or bevacizumab. Mean age was 57.1 +/- 21.7; 60.6% of the patients were male and 25% had autoimmune antecedents. Among the 55 suspected drugs, three were classified as "probable" and 28 as "possible" according to George scale. In both vaccinal and other cases, median delay was 14 days, median platelet value at nadir was<10000 ul(-1) and hemorrhagic symptoms were rarely severe (only 2 gastrointestinal hemorrhages). Specific treatment was introduced in 45 (76.3%) patients. Five drug-induced cases led to chronicity. Among them, ezetimibe was suspected in two reports. In the FPVD, DTP, MMR, and influenza vaccines are the most often reported vaccines inducing ITP, perhaps because of their wide use. Our study confirmed that NSAIDs, abciximab, and acetaminophen frequently trigger ITP. It also allows to suspect other drugs like serotonin reuptake inhibitors or bevacizumab. Ezetimibe may induce chronic ITP. Drug-induced ITP is rarely severe. Finally, this study also shows that chronicity of ITP does not rule out the possibility of an iatrogenic cause. PMID- 22098131 TI - Evaluation of hemostatic balance in blood from patients with polycythemia vera by means of thromboelastography: the effect of isovolemic erythrocytapheresis. AB - Polycythemia vera (PV) is associated with an increased frequency of thrombotic complications. This study was undertaken to evaluate the hemostatic balance in the blood of PV patients by means of thromboelastography (TEG). The effect of isovolemic erythrocytapheresis (ECP) on the hemostasis of PV patients was also studied. We assessed the coagulation status of 76 PV patients undergoing ECP and 50 of healthy controls. TEG measurements were performed immediately before and after the ECP procedure. Coagulation was triggered by recalcification in freshly collected citrated blood. We recorded clotting time (R), alpha angle, and maximum amplitude (MA) of the clot. The results presented here show that, compared with healthy controls, PV patients demonstrated an increase in alpha angle (p<0.005) and in MA (p=0.14). In the subgroup of PV patients with high (>440 * 10(9)l(-1)) platelet (PLT) count, differences in MA (p<0.01) and alpha angle (p<0.001) were more significant. Following ECP procedure, a significant (p <= 0.01) reduction of R time, a rise of alpha angle, and MA were observed, indicating augmentation of a hypercoagulable state. In PV patients, the rise in alpha angle positively correlated (r=0.549) with platelet count but not with the number of erythrocytes and leukocytes. Following ECP, this correlation was reduced (r=0.382). Dilution (with saline) of blood from PV patients and of healthy controls, to a degree similar to that used during the ECP procedure, resulted in reduction of R and rise of the alpha angle. In conclusion, TEG measurements show that the majority of PV patients demonstrate abnormal hemostasis in which a major role is played by platelets rather than plasma factors. The hypercoagulable state in PV patients is significantly augmented following the ECP and may be related to the hemodilution intrinsically included in this procedure. TEG may help to assess the thrombotic risk in individual PV patients. PMID- 22098132 TI - Characterizing organic monolithic columns using capillary flow porometry and scanning electron microscopy. AB - Polyethylene glycol diacrylate monoliths prepared using different amounts of monomer, porogen ratio, and capillary dimensions were characterized using capillary flow porometry (CFP) and scanning electron microscopy (SEM). Our results reveal good agreement between SEM and CFP measurements for through-pore size distribution. The CFP measurements for monoliths prepared by the same procedure in capillaries with different diameters (i.e., 75, 150, and 250 MUm) clearly confirmed a change in through-pore size distribution with capillary diameter, thus, certifying the need for in-column measurement techniques over bulk measurements (e.g., mercury intrusion porosimetry). The mean through-pore size varied from 3.52 to 1.50 MUm with a change in capillary diameter from 75 to 250 MUm. Consistent mean through-pore size distribution for capillary columns with the same internal diameter but with different lengths (1.5, 2, and 3 cm) confirms the high interconnectivity of the pores and independence of CFP measurements with respect to capillary length. CFP and SEM measurements not only allow pore structure analysis but also prediction of relative column performance. Monoliths with narrow through-pore size distribution (0.8-1.2 MUm), small mean through-pore size, and thin skeletal size (0.55 MUm) gave the best performance in terms of efficiency for polyethylene glycol diacrylate monoliths. PMID- 22098133 TI - Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy. AB - BACKGROUND AND AIM: Helicobacter pylori eradication clearly decreases peptic ulcer recurrence rates. H. pylori eradication is achieved in 70-90% of cases, but treatment failures due to poor patient compliance and resistant organisms do occur. Lactobacillus gasseri can suppress both clarithromycin-susceptible and resistant strains of H. pylori in vitro. The aim of this study was to determine the effect of pretreatment with L. gasseri- containing yogurt on H. pylori eradication. We conducted a randomized, controlled clinical trial in patients with H. pylori infection. METHODS: A total of 229 patients were randomized into either a 1-week triple therapy of rabeprazole (10 mg bid), amoxicillin (750 mg bid), and clarithromycin (200 mg bid) or triple therapy plus L. gasseri containing yogurt. In the yogurt-plus-triple therapy groups, yogurt containing L. gasseri OLL2716 (112 g) was given twice daily for 4 weeks (3 weeks pretreatment and also 1 week during eradication therapy). Clarithromycin resistance was determined by the detection of a mutation in 23S rRNA using nested polymerase chain reaction and the direct sequencing of DNA from pretreatment feces. H. pylori eradication was diagnosed based on the urea breath test and a stool antigen test after 8 weeks of eradication. RESULTS: The status of H. pylori susceptibility to clarithromycin was successively determined in 188 out of 229 samples. The rate of infection with clarithromycin-resistant strains of H. pylori was 27.1%. Overall eradication (intention to treat/per protocol) was 69.3/74.5% for the triple-only group, and 82.6/85.6% for the yogurt-plus-triple group (P = 0.018/P = 0.041). Eradication of primary clarithromycin-resistant strains tended to be higher for yogurt-plus-triple therapy than triple-only therapy (38.5 vs 28.0%, respectively, P = 0.458). CONCLUSION: This study confirmed that the major cause of treatment failure is resistance to clarithromycin. A 4-week treatment with L. gasseri-containing yogurt improves the efficacy of triple therapy in patients with H. pylori infection. PMID- 22098134 TI - AGD1, a class 1 ARF-GAP, acts in common signaling pathways with phosphoinositide metabolism and the actin cytoskeleton in controlling Arabidopsis root hair polarity. AB - The Arabidopsis thaliana AGD1 gene encodes a class 1 adenosine diphosphate ribosylation factor-gtpase-activating protein (ARF-GAP). Previously, we found that agd1 mutants have root hairs that exhibit wavy growth and have two tips that originate from a single initiation point. To gain new insights into how AGD1 modulates root hair polarity we analyzed double mutants of agd1 and other loci involved in root hair development, and evaluated dynamics of various components of root hair tip growth in agd1 by live cell microscopy. Because AGD1 contains a phosphoinositide (PI) binding pleckstrin homology (PH) domain, we focused on genetic interactions between agd1 and root hair mutants altered in PI metabolism. Rhd4, which is knocked-out in a gene encoding a phosphatidylinositol-4-phosphate (PI-4P) phosphatase, was epistatic to agd1. In contrast, mutations to PIP5K3 and COW1, which encode a type B phosphatidylinositol-4-phosphate 5-kinase 3 and a phosphatidylinositol transfer protein, respectively, enhanced the root hair defects of agd1. Enhanced root hair defects were also observed in double mutants to AGD1 and ACT2, a root hair-expressed vegetative actin isoform. Consistent with our double-mutant studies, targeting of tip growth components involved in PI signaling (PI-4P), secretion (RABA4b) and actin regulation (ROP2), were altered in agd1 root hairs. Furthermore, tip cytosolic calcium ([Ca2+](cyt) ) oscillations were disrupted in root hairs of agd1. Taken together, our results indicate that AGD1 links PI signaling to cytoskeletal-, [Ca2+](cyt-) , ROP2-, and RABA4b-mediated root hair development. PMID- 22098135 TI - Malaria prevalence and treatment of febrile patients at health facilities and medicine retailers in Cameroon. AB - OBJECTIVE: To investigate the quality of malaria case management in Cameroon 5 years after the adoption of artemisinin-based combination therapy (ACT). Treatment patterns were examined in different types of facility, and the factors associated with being prescribed or receiving an ACT were investigated. METHODS: A cross-sectional cluster survey was conducted among individuals of all ages who left public and private health facilities and medicine retailers in Cameroon and who reported seeking treatment for a fever. Prevalence of malaria was determined by rapid diagnostic tests (RDTs) in consenting patients attending the facilities and medicine retailers. RESULTS: Among the patients, 73% were prescribed or received an antimalarial, and 51% were prescribed or received an ACT. Treatment provided to patients significantly differed by type of facility: 65% of patients at public facilities, 55% of patients at private facilities and 45% of patients at medicine retailers were prescribed or received an ACT (P = 0.023). The odds of a febrile patient being prescribed or receiving an ACT were significantly higher for patients who asked for an ACT (OR = 24.1, P < 0.001), were examined by the health worker (OR = 1.88, P = 0.021), had not previously sought an antimalarial for the illness (OR = 2.29, P = 0.001) and sought treatment at a public (OR = 3.55) or private facility (OR = 1.99, P = 0.003). Malaria was confirmed in 29% of patients and 70% of patients with a negative result were prescribed or received an antimalarial. CONCLUSIONS: Malaria case management could be improved. Symptomatic diagnosis is inefficient because two-thirds of febrile patients do not have malaria. Government plans to extend malaria testing should promote rational use of ACT; though, the introduction of rapid diagnostic testing needs to be accompanied by updated clinical guidelines that provide clear guidance for the treatment of patients with negative test results. PMID- 22098139 TI - A phase I study to characterize the multiple-dose pharmacokinetics, pharmacodynamics and safety of new enteric-coated triflusal formulations in healthy male volunteers. AB - OBJECTIVES: An enteric-coated formulation of triflusal (triflusal EC), an antiplatelet agent, was developed to reduce the high incidence of gastrointestinal adverse events (AEs). The aim of this study is to compare the pharmacokinetics, pharmacodynamics and safety of triflusal EC with triflusal in healthy Korean male subjects to determine bioequivalence and non-inferiority for the purposes of marketing approval. METHODS: A randomized, open-label, two period, crossover study was conducted in 38 subjects. Either triflusal EC or triflusal was administered orally as a single 900 mg loading dose (day 1) followed by eight 600 mg/day maintenance doses on days 2 - 9, with a 13-day washout period. The plasma concentrations of 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), the predominant active metabolite of triflusal, were assessed after administration of the loading dose, using HPLC/MS/MS. The platelet aggregation response to arachidonic acid was determined using turbidimetric aggregometry. RESULTS: The 90% CIs, for the geometric mean ratios of the log-transformed AUC(tau) and C(max) of HTB were seen to be within the predetermined range of 0.8 1.25. Triflusal EC was also shown to be non-inferior in its anti-aggregatory effect. No serious AEs were reported during this study. CONCLUSIONS: The pharmacokinetic and pharmacodynamic profiles of the two triflusal formulations met the requirements for bioequivalence and non-inferiority, respectively. Both formulations were well tolerated. PMID- 22098140 TI - Improvements in the reliability of in vitro genotoxicity testing. AB - INTRODUCTION: In vitro genotoxicity assays have a high sensitivity to detect rodent carcinogens, but mammalian cell tests have a propensity for misleading positive results (poor specificity). Recent data show a greater risk of misleading positive results in p53-deficient rodent cell lines than in p53 competent human cells. Measures of cytotoxicity, source and stability of cells used are also important. AREAS COVERED: In this review, potential reduction in the top concentration for testing (10 mM) is discussed. Indirect effects on non DNA targets, which may not be relevant for humans or may exhibit a threshold, have been identified. EXPERT OPINION: The reliability of in vitro genotoxicity tests could be improved by selecting p53-proficient, human cells. The provenance and stability of the cells used should be demonstrated. Measures of cytotoxicity based on cell proliferation should be used. Lowering the top concentration for testing from 10 mM to 4 mM or 2000 MUg/ml, whichever is the lower, as proposed by some experts, would seem to be justified. Artefacts that may be caused by reaction of test substance with culture medium should be avoided. Better understanding and investigation of the potential for threshold and irrelevant modes of action are encouraged. PMID- 22098141 TI - Performance of lecithin-sphingomyelin ratio as a reflex test for documenting fetal lung maturity in late preterm and term fetuses. AB - OBJECTIVE: To determine if infants delivered after immature or indeterminate TDx FLM II testing and a mature reflex test are at increased risk for neonatal respiratory complications. METHODS: The primary analysis compared neonatal respiratory morbidity (RDS or TTN) in 34-39-week fetuses delivered after either (i) mature TDx-FLM II testing, or (ii) indeterminate or immature TDx-FLM II and a positive reflex test (PG or L/S ratio). RESULTS: Fifty patients delivered after mature TDx-FLM II, and 30 after immature or indeterminate TDx-FLM II with an L/S >= 2.0. Respiratory morbidity was significantly higher in the group delivered after mature reflex testing compared with mature TDx-FLM II (23% vs. 2%, p < 0.01). When PG was present, there were no cases of RDS or TTN. CONCLUSIONS: Utilizing L/S ratios as a reflex test to confirm lung maturity was associated with a high risk for respiratory morbidity, particularly when PG was not present. PMID- 22098143 TI - Family-centred or family-censored care? PMID- 22098136 TI - Peroxiredoxins in parasites. AB - SIGNIFICANCE: Parasite survival and virulence relies on effective defenses against reactive oxygen and nitrogen species produced by the host immune system. Peroxiredoxins (Prxs) are ubiquitous enzymes now thought to be central to such defenses and, as such, have potential value as drug targets and vaccine antigens. RECENT ADVANCES: Plasmodial and kinetoplastid Prx systems are the most extensively studied, yet remain inadequately understood. For many other parasites our knowledge is even less well developed. Through parasite genome sequencing efforts, however, the key players are being discovered and characterized. Here we describe what is known about the biochemistry, regulation, and cell biology of Prxs in parasitic protozoa, helminths, and fungi. At least one Prx is found in each parasite with a sequenced genome, and a notable theme is the common patterns of expression, localization, and functionality among sequence-similar Prxs in related species. CRITICAL ISSUES: The nomenclature of Prxs from parasites is in a state of disarray, causing confusion and making comparative inferences difficult. Here we introduce a systematic Prx naming convention that is consistent between organisms and informative about structural and evolutionary relationships. FUTURE DIRECTIONS: The new nomenclature should stimulate the crossfertilization of ideas among parasitologists and with the broader redox research community. The diverse parasite developmental stages and host environments present complex systems in which to explore the variety of roles played by Prxs, with a view toward parlaying what is learned into novel therapies and vaccines that are urgently needed. PMID- 22098144 TI - Residual ridge atrophy in complete denture wearers and relationship with densitometric values of a cervical spine: a hierarchical regression analysis. AB - BACKGROUND: The rate of residual ridge atrophy (RRR) and its association with mineral density of other bones have not yet been fully explained. OBJECTIVE: To measure RRR over a 5-year period in complete denture wearers and relate it to the density of a cervical spine (CSBD). MATERIALS AND METHODS: Sixty-two patients (different gender, age, body mass index, duration of edentulousness (DE) and different denture-wearing habits) participated. A copper stepwedge was attached to the cassette, and 50 lateral radiograms met the criteria to be included. RESULTS: A significant decrease in vertical height was observed in all measured sites. The amount of RRR was highest in frontal areas of both jaws and decreased gradually towards lateral regions. Hierarchical regression analysis revealed that the amount of RRR in the maxillary frontal area could be explained up to 48.4% by the variable DE and only up to 6.1% by the CSBD, while gender had almost no influence (1%). Similar results were obtained for the lateral maxillary RRR (33.9%; 7%; 2%), frontal mandibular RRR (40; 8.4; 0.4%) and lateral mandibular RRR (31.5%; 3.4%; 7.7%). CONCLUSION: Skeletal bone density, reflecting systemic and hereditary factors, is weakly related to RRR (3.4-8.4%). PMID- 22098145 TI - Methylated arsenic species in plants originate from soil microorganisms. AB - * Inorganic arsenic (iAs) is a ubiquitous human carcinogen, and rice (Oryza sativa) is the main contributor to iAs in the diet. Methylated pentavalent As species are less toxic and are routinely found in plants; however, it is currently unknown whether plants are able to methylate As. * Rice, tomato (Solanum lycopersicum) and red clover (Trifolium pratense) were exposed to iAs, monomethylarsonic acid (MMA(V)), or dimethylarsinic acid (DMA(V)), under axenic conditions. Rice seedlings were also grown in two soils under nonsterile flooded conditions, and rice plants exposed to arsenite or DMA(V) were grown to maturity in nonsterile hydroponic culture. Arsenic speciation in samples was determined by HPLC-ICP-MS. * Methylated arsenicals were not found in the three plant species exposed to iAs under axenic conditions. Axenically grown rice was able to take up MMA(V) or DMA(V), and reduce MMA(V) to MMA(III) but not convert it to DMA(V). Methylated As was detected in the shoots of soil-grown rice, and in rice grain from nonsterile hydroponic culture. GeoChip analysis of microbial genes in a Bangladeshi paddy soil showed the presence of the microbial As methyltransferase gene arsM. * Our results suggest that plants are unable to methylate iAs, and instead take up methylated As produced by microorganisms. PMID- 22098146 TI - Activity-aware clustering of high throughput screening data and elucidation of orthogonal structure-activity relationships. AB - From a medicinal chemistry point of view, one of the primary goals of high throughput screening (HTS) hit list assessment is the identification of chemotypes with an informative structure-activity relationship (SAR). Such chemotypes may enable optimization of the primary potency, as well as selectivity and phamacokinetic properties. A common way to prioritize them is molecular clustering of the hits. Typical clustering techniques, however, rely on a general notion of chemical similarity or standard rules of scaffold decomposition and are thus insensitive to molecular features that are enriched in biologically active compounds. This hinders SAR analysis, because compounds sharing the same pharmacophore might not end up in the same cluster and thus are not directly compared to each other by the medicinal chemist. Similarly, common chemotypes that are not related to activity may contaminate clusters, distracting from important chemical motifs. We combined molecular similarity and Bayesian models and introduce (I) a robust, activity-aware clustering approach and (II) a feature mapping method for the elucidation of distinct SAR determinants in polypharmacologic compounds. We evaluated the method on 462 dose-response assays from the Pubchem Bioassay repository. Activity-aware clustering grouped compounds sharing molecular cores that were specific for the target or pathway at hand, rather than grouping inactive scaffolds commonly found in compound series. Many of these core structures we also found in literature that discussed SARs of the respective targets. A numerical comparison of cores allowed for identification of the structural prerequisites for polypharmacology, i.e., distinct bioactive regions within a single compound, and pointed toward selectivity-conferring medchem strategies. The method presented here is generally applicable to any type of activity data and may help bridge the gap between hit list assessment and designing a medchem strategy. PMID- 22098147 TI - The potential role of Marginal Structural Models (MSMs) in testing the effectiveness of antidepressants in the treatment of patients with major depression in everyday clinical practice. AB - OBJECTIVES: To better evaluate the effectiveness of antidepressant drugs in the treatment of major depression in clinical practice. METHODS: A simulation experiment was used to illustrate an application of marginal structural models (MSMs) via inverse probability of treatment weighting (IPTW) approach in the context of non-randomized data on N = 1,000 depressed subjects, initially subjected to "watchful waiting". In simulation we assumed that subjects with worse intermediate outcome have a higher probability of being subsequently assigned to antidepressant treatment while those who receive antidepressant treatment are more likely to reach remission and less likely to reach relapse state. The outcomes from multiple (500) simulated data sets are analyzed using simple unadjusted analysis based on logistic regression and using MSM. RESULTS: In contrast to unadjusted analysis, but consistent with the treatment assumptions, using MSM via IPTW results in strong evidence of the effectiveness of the antidepressant treatment. Furthermore MSM via IPTW substantially reduces the probability of wrongly rejecting the null hypothesis. However, the instability of weights due to the sparse data and incorrectly specified MSM may still result in inflation of Type I error rates. CONCLUSIONS: MSMs may allow evaluating the causal effects associated with antidepressant treatment from the data observed in clinical practice. PMID- 22098148 TI - Low plasma vascular endothelial growth factor (VEGF) associated with completed suicide. AB - OBJECTIVES: Immunological differences have previously been associated with depression and suicidal behaviour. Several cytokines have been identified as potentially important in understanding the pathophysiology of mood disorders and suicidality. Here we aimed to identify new inflammatory biomarkers for suicide prediction. METHODS: Plasma concentrations of interleukin (IL) 1-a , IL1-b, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFNG), tumor necrosis factor-a (TNF a), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) were measured in 58 suicide attempters with a high throughput automated biochip immunoassay system. Patients were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Suicide Intent Scale (SIS). All patients were followed up for cause of death. RESULTS: We found significantly lower levels of VEGF in the seven patients who upon a mean follow-up of 13 years were found to have completed suicide. VEGF also showed a trend for negative correlation with the planning subscale of SIS. A trend could be shown for lower IL-2 and for higher IFNG levels in suicide victims. CONCLUSIONS: Our study provides further support for a role of inflammation in the pathophysiology of suicidality. VEGF may be related with suicide risk. PMID- 22098149 TI - Surface behavior, aggregation and phase separation of aqueous mixtures of dodecyl trimethylammonium bromide and sodium oligoarene sulfonates: the transition to polyelectrolyte/surfactant behavior. AB - The properties and phase diagrams of aqueous mixtures of dodecyltrimethylammonium bromide (C(12)TAB) with the sodium oligoarene sulphonates (POSn), POS2, POS3, POS4, and POS6 have been studied using surface tension and neutron reflectometry to study the surface, and neutron small angle scattering and fluorescence to study the bulk solution. The behavior of POS2 and POS3 is reasonably consistent with mixed micelles of C(12)TAB and POSn-(C(12)TA)(n). These systems exhibit a single critical micelle concentration (CMC) at which the surface tension reaches the usual plateau. This is contrary to a recent report which suggests that the onset of the surface tension plateau does not coincide with the CMC. In the POS3 system, the micelles conform to the core-shell model, are slightly ellipsoidal, and have aggregation numbers in the range 70-100. In addition, the dissociation constant for ionization of the micelles is significantly lower than for free C(12)TAB micelles, indicating binding of the POS3 ion to the micelles. Estimation of the CMCs of the POSn-(C(12)TA)(n) from n = 1-3 assuming ideal mixing of the two component surfactants and the observed values of the mixed CMC gives values that are consistent with the nearest related gemini surfactant. The POS4 and POS6 systems are different. They both phase separate slowly to form a dilute and a concentrated (dense) phase. Fluorescence of POS4 has been used to show that the onset of aggregation of surfactant (critical aggregation concentration, CAC) occurs at the onset of the surface tension plateau and that, at the slightly higher concentration of the phase separation, the concentration of POS4 and C(12)TAB in the dilute phase is at or below its concentration at the CAC, that is, this is a clear case of complex coacervation. The surface layer of the C(12)TA ion in the surface tension plateau region, studied directly by neutron reflectometry, was found to be higher than a simple monolayer (observed for POS2 and POS3) for both the POS4 and POS6 systems. In POS6 this evolved after a few hours to a structure consisting of a monolayer with an attached subsurface bilayer, closely resembling that observed for one class of polyelectrolyte/surfactant mixtures. It is suggested that this structured layer, which must be present on the surface of the dilute phase of the coacervated system, is a thin wetting film of the dense phase. The close resemblance of the properties of the POS6 system to that of one large group of polyelectrolyte/surfactant mixtures shows that the surface behavior of oligoion/surfactant mixtures can quickly become representative of that of true polyelectrolyte/surfactant mixtures. In addition, the more precise characterization possible for the POS6 system identifies an unusual feature of the surface behavior of some polyelectrolyte/surfactant systems and that is that the surface tension can remain low and constant through a precipitation/coacervation region because of the characteristics of two phase wetting. The well-defined fixed charge distribution in POS6 also suggests that rigidity and charge separation are the factors that control whether a given system will exhibit a flat surface tension plateau or the alternative of a peak on the surface tension plateau. PMID- 22098150 TI - Synthesis of 1,2,4,5-tetrasubstituted imidazoles by a sequential aza Wittig/Michael/isomerization reaction. AB - Carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aryl isocyanates, reacted with secondary amines in the presence of a catalytic amount of sodium alkoxide to give 1,2,4,5-tetrasubstituted imidazoles 7 in good yields. However, 4-acylimidazoles 11 were obtained, as phenols were used in the presence of a catalytic amount of potassium carbonate due to further air oxidation of the expected products 10. PMID- 22098151 TI - Pachyonychia congenita patients with mutations in KRT6A have more extensive disease compared with patients who have mutations in KRT16. AB - BACKGROUND: Pachyonychia congenita (PC) is an autosomal dominant, very rare keratin disorder caused by mutations in any of at least four genes (KRT6A, KRT6B, KRT16 or KRT17), which can lead to hypertrophic nail dystrophy and palmoplantar keratoderma, among other manifestations. Classically, patients with mutations in KRT6A and KRT16 have been grouped to the PC-1 subtype (Jadassohn-Lewandowsky type) and KRT6B and KRT17 to PC-2 (Jackson-Lawler type). OBJECTIVES: To describe clinical heterogeneity among patients with PC who have genetic mutations in KRT6A and KRT16. METHODS: In 2004, the Pachyonychia Congenita Project established the International PC Research Registry (IPCRR) for patients with PC. All patients reporting here underwent genetic testing and responded to a standardized, validated survey about their PC symptoms. We report results from 89 patients with KRT6A mutations and 68 patients with KRT16 mutations. RESULTS: Patients with PC who have KRT6A and KRT16 mutations display distinct phenotypic differences. Patients with PC-K6a experience earlier onset, more extensive nail disease and more substantial disease outside palms and soles, as they reported a higher prevalence of oral leucokeratosis (P < 0.001), cysts (P < 0.001) and follicular hyperkeratosis (P < 0.001) compared with their PC-K16 counterparts. CONCLUSION: Phenotypic differences between patients with KRT6A and KRT16 mutations support adoption of a new classification system based on the mutant gene (PC-6a, PC-16) rather than the PC-1 nomenclature. PMID- 22098152 TI - Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma. AB - BACKGROUND AND AIM: Patients with hepatocellular carcinoma (HCC) that is refractory to repeated transarterial chemoembolization (TACE) are considered for systemic therapy, but TACE refractoriness is not well defined. The aim of this study was to determine the characteristics of patients whose HCC is refractory to repetitive TACE. METHODS: We evaluated 264 patients with intermediate-stage HCC who underwent TACE between January 2006 and September 2009. We designated the development of vascular invasion or extrahepatic spread during follow up as "stage progression" (SP), and hypothesized that SP might be the surrogate end point for TACE refractoriness. RESULTS: The median follow up was 18.2 months, and median number of TACE was 3.0 (range, 1-13). Median time-to-progression was 5.5 months (95% confidence interval, 4.8-6.2), and median overall survival was 25.3 months (95% confidence interval, 21.6-29.0). We classified the patients according to disease course as: no progressive disease (PD(-); n = 33); PD without SP (PD(+)SP(-); n = 113); PD followed by SP (PD->SP; n = 47); and simultaneous PD and SP (PD&SP; n = 64). PD(-) and PD(+)SP(-) groups showed no difference in overall survival, PD->SP group had worse overall survival than PD(-) and PD(+)SP( ) groups, and PD&SP group had the worst overall survival. The significant prognostic factors for SP-free survival were development of PD and need for three sessions of TACE during the first 6 months. CONCLUSIONS: SP-free survival can be regarded as an end-point for TACE refractoriness. Development of progression or need for three sessions of TACE within the first 6 months could be predictive of TACE refractoriness. PMID- 22098153 TI - Scutellaria litwinowii induces apoptosis through both extrinsic and intrinsic apoptotic pathways in human promyelocytic leukemia cells. AB - Scutellaria is a genus of Lamiaceae with known antiproliferative potentials. Scutellaria litwinowii Bornm. & Sint. ex Bornm. is one of the Iranian species of Scutellaria. Although there are widespread reports about the cytotoxic and antitumor effects of some species of this genus, research on the molecular mechanism responsible for the anticancer effects of S. litwinowii has not yet been conducted. In the current study, the apoptotic effects of S. litwinowii on 2 myeloid cell lines, apoptosis-proficient HL60 cells and apoptosis-resistant K562 cells, were analyzed. An increase in the activity of caspases-3, -8, and -9, poly (ADP ribose) polymerase (PARP) cleavage, detection of phosphatidylserine on the outer layer of cell membrane and sub-G1 peak in the flow cytometry histogram of treated cells, suggested the induction of apoptosis. S. litwinowii also increased the Bax/Bcl-2 ratio. It could be concluded that S. litwinowii induced apoptosis in both apoptosis-proficient and apoptosis-resistant leukemic cells and it might be considered as a novel candidate in the treatment of hematological malignancies. PMID- 22098154 TI - Evaluation of the kinematic parameters of normal-paced gait in subjects with gonarthrosis and the influence of gonarthrosis on the function of the ankle joint and hip joint. AB - The aim of the study was to assess the variability of parameters characterising the gait of persons suffering from degenerative changes of the knee joint and their influence on the ankle and hip joints. The values of the angular changes in the knee, ankle and hip joints in the three planes of motion were assessed. Locomotion tests were performed on 27 persons, aged between 60 and 74, using Vicon 250, the three-dimensional analysis system. The sharpest deviations from the results of the control group were revealed in the transverse and frontal planes. Degenerative knee joint disease has changed the gait stereotype causing a reduction in the economy of gonarthrosis patients' locomotion, the influence of the disease on the function of the neighbouring joints is also distinctly marked. PMID- 22098155 TI - PLOD2 induced under hypoxia is a novel prognostic factor for hepatocellular carcinoma after curative resection. AB - BACKGROUND: Under hypoxia, tumour cells undergo genetic and adaptive changes that allow their survival. Previously, we reported that high expression of hypoxia inducible factor (HIF)-1 was a significant predictive factor for recurrence in hepatocellular carcinoma (HCC). Hypoxia also stimulates expression of procollagen lysine, 2-oxoglutarate 5-dioxygenase (PLOD) genes via the HIF-1 pathway. AIMS: The aim was to evaluate the relationship between hypoxia stress and expression of PLOD genes in HCC in vitro and to identify a new prognostic marker in HCC patients. METHODS: The PLOD2 expression was assessed under hypoxia in hepatoma cell lines and characterized in 139 HCC samples following hepatic resection using microarray experiments, quantitative RT-PCR and immunohistochemistry. Prognostic factors in HCC patients were assessed using univariate and multivariate analyses. RESULTS: The PLOD2 expression was induced under the hypoxia in vitro. Disease free survival in the high PLOD2 expression group of HCC patients was significantly shorter when compared with the low-expression group (P = 0.002). In a subset of HCCs, we found that the PLOD2 expression of microarray was correlated with data of quantitative RT-PCR and immunohistochemistry. Of clinicopathological factors, PLOD2 expression was significantly correlated with tumour size (P = 0.022) and macroscopic intrahepatic metastasis (P = 0.049). In univariate analysis, six prognostic factors (tumour multiplicity, macroscopic intrahepatic metastasis, histological grade, microscopic portal invasion, microscopic intrahepatic metastasis and PLOD2 expression) were significant for disease-free survival. PLOD2 expression was identified as a significant, independent factor of poor prognosis (P = 0.013). CONCLUSIONS: PLOD2 is a potential novel prognostic factor for HCC patients following surgery. PMID- 22098156 TI - Cancer stem cell marker ALDH1 expression is associated with lymph node metastasis and poor survival in esophageal squamous cell carcinoma: a study from high incidence area of northern China. AB - Tumor recurrence and metastasis is the leading cause of death in esophageal squamous cell carcinoma (ESCC). Cancer stem cell (CSC) may be responsible for tumor growth and maintenance of aggressive behavior. Aldehyde dehydrogenase 1 (ALDH1) has been proposed as one of the possible candidates for a CSC marker. The expression of ALDH1 may be correlated with the clinicopathologic factor and clinical outcome of patients with ESCC. The purpose of this study was to investigate the expression of ALDH1 protein in human ESCC tissues, and evaluated the clinical implication of ALDH1 expression for these patients. All 79 patients who underwent esophagectomy for ESCC between January 2005 and June 2006 were enrolled in this study. The expression of ALDH1 in ESCC and adjacent noncancerous tissues was analyzed by immunohistochemistry. ALDH1 was mainly expressed in ESCC cell nucleus. For the 79 ESCC patients, increased nuclear accumulation of ALDH1 was found in 12 (15.2%) specimens. ALDH1 expression was correlated with poor histological differentiation (P= 0.003), lymph node metastasis (P= 0.011), and late pathologic TNM classification (pTNM) staging (P= 0.003). Patients in ALDH1 positive group had a significantly poor 5-year overall survival than those in the negative group (8.3% vs. 52.2%, P= 0.025). We have demonstrated for the first time that the CSC marker, ALDH1, is expressed in human ESCC. The expression of ALDH1 protein in nucleus of the ESCC is significantly associated with lymph node metastasis and poor survival. Our results highly indicate the involvement of ALDH1 in the aggressive behavior of ESCC. PMID- 22098157 TI - Embracing an era of rising family quality of life research. PMID- 22098158 TI - Relevance-driven information search in "pseudodiagnostic" reasoning. AB - When faced with two competing hypotheses, people sometimes prefer to look at multiple sources of information in support of one hypothesis rather than to establish the diagnostic value of a single piece of information for the two hypotheses. This is termed pseudodiagnostic reasoning and has often been understood to reflect, among other things, poor information search strategies. Past research suggests that diagnostic reasoning may be more easily fostered when participants seek data to help in the selection of one of two competing courses of action as opposed to situations where they seek data to help infer which of two competing hypotheses is true. In the experiment reported here, we provide the first empirical evidence demonstrating that manipulating the relevance of the feature for which participants initially receive information determines whether they will make a nominally diagnostic or pseudodiagnostic selection. The discussion of these findings focuses on implications for the ability to engage in diagnostic hypothesis testing. PMID- 22098160 TI - Lysosomal function and dysfunction: mechanism and disease. AB - SIGNIFICANCE: Lysosomes are organelles in which cellular degradation occurs in a controlled manner, separated from other cellular components. As several pathways terminate in the lysosome, lysosomal dysfunction has a profound impact on cell homeostasis, resulting in manifold pathological situations, including infectious diseases, neurodegeneration, and aging. RECENT ADVANCES: Lysosomal biology demonstrates that in addition to regulating the final steps of catabolic processes, lysosomes are essential up-stream modulators of autophagy and other essential lysosomal pathways. FUTURE DIRECTIONS AND CRITICAL ISSUES: Lysosomal membrane permeabilization offers therapeutic potential in the treatment of cancer, though the molecular regulators of this process remain obscure. This review focuses on recent discoveries in lysosomal function and dysfunction, primarily in in vivo situations. PMID- 22098159 TI - Deregulation of Hippo kinase signalling in human hepatic malignancies. AB - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and hepatoblastoma (HB) are the main hepatic malignancies with limited treatment options and high mortality. Recent studies have implicated Hippo kinase pathway in cancer development, but detailed analysis of Hippo kinase signalling in human hepatic malignancies, especially CC and HB, is lacking. METHODS: We investigated Hippo kinase signalling in HCC, CC and HB using cells and patient samples. RESULTS: Increased expression of yes-associated protein (Yap), the downstream effector of the Hippo kinase pathway, was observed in HCC cells, and siRNA mediated knockdown of Yap resulted in decreased survival of HCC cells. The density-dependent activation of Hippo kinase pathway characteristic of normal cells was not observed in HCC cells and CCLP cells, a cholangiocarcinoma cell line. Immunohistochemistry of Yap in HCC, CC and HB tissues indicated extensive nuclear localization of Yap in majority of tissues. Western blot analysis performed using total cell extracts from patient samples and normal livers showed extensive activation of Yap. Marked induction of Glypican-3, CTGF and Survivin, the three Yap target genes was observed in the tumour samples. Further analysis revealed significant decrease in expression and activity of Lats kinase, the main upstream regulator of Yap. However, no change in activation of Mst-2 kinase, the upstream regulator of Lats kinase was observed. CONCLUSIONS: These data show that Yap induction mediated by inactivation of Lats is observed in hepatic malignancies. These studies highlight Hippo kinase pathway as a novel therapeutic target for hepatic malignancies. PMID- 22098161 TI - Barley grains, deficient in cytosolic small subunit of ADP-glucose pyrophosphorylase, reveal coordinate adjustment of C:N metabolism mediated by an overlapping metabolic-hormonal control. AB - The barley Riso16 mutation leads to inactivation of cytosolic ADP-Glc pyrophosphorylase, and results in decreased ADP-Glc and endospermal starch levels. Here we show that this mutation is accompanied by a decrease in storage protein accumulation and seed size, which indicates that alteration of a single enzymatic step can change the network of storage metabolism as a whole. We used comprehensive transcript, metabolite and hormonal profiling to compare grain metabolism and development of Riso16 and wild-type endosperm. Despite increased sugar availability in mutant endosperm, glycolytic intermediates downstream of hexose phosphates remained unchanged or decreased, while several glycolytic enzymes were downregulated at the transcriptional level. Metabolite and transcript profiling also indicated an inhibition of the tricarboxylic acid cycle at the level of mitochondrial nicotinamide adenine dinucleotide (NAD)-isocitrate dehydrogenase and an attendant decrease in alpha-ketoglutarate and amino acids levels in Riso16, compared with wild type. Decreased levels of cytokinins in Riso16 endosperm suggested co-regulation between starch synthesis, abscisic acid (ABA) deficiency and cytokinin biosynthesis. Comparative cis-element analysis in promoters of jointly downregulated genes in Riso16 revealed an overlap between metabolic and hormonal regulation, which leds to a coordinated downregulation of endosperm-specific and ABA-inducible gene expression (storage proteins) together with repression by sugars (isocitrate dehydrogenase, amylases). Such co regulation ensured that decreased carbon fluxes into starch lead to a coordinated inhibition of glycolysis, amino acid and storage proteins biosynthesis, which is useful in the prevention of osmotic imbalances and oxidative stress due to increased accumulation of sugars. PMID- 22098162 TI - Early use of high-dose riboflavin in a case of Brown-Vialetto-Van Laere syndrome. AB - Brown-Vialetto-Van Laere syndrome (BVVLS) is a genetic condition caused by a mutation in the C20orf54 gene, which also codes for an intestinal riboflavin transporter. We report the case of a female who presented at 22 months with acute onset stridor and generalized muscle weakness, in whom a genetic diagnosis of BVVLS was made, and whose symptoms improved on therapy with high-dose riboflavin. She had previously been developing normally and was able to walk at 11 months, then developed progressive muscle weakness at 22 months, and within 2 weeks was unable to sit without support. She also demonstrated stridor and paradoxical breathing indicating diaphragmatic weakness, and required continuous non-invasive ventilation (NIV) through a tracheostomy. After treatment with riboflavin she was able to walk unaided, and her Gross Motor Functional Classification level improved from level IV to level I, having fully regained the motor function she showed before symptom onset. There were no longer signs of diaphragmatic paralysis while on NIV, and she was able to tolerate 10-minute periods off NIV before paradoxical breathing again became apparent. We therefore recommend that in all cases suspected to be in the BVVLS or Fazio-Londe spectrum, early treatment with high-dose riboflavin must be considered. PMID- 22098163 TI - Aptamer capturing of enzymes on magnetic beads to enhance assay specificity and sensitivity. AB - Activity and specificity of enzyme molecules are important to enzymatic reactions and enzyme assays. We describe an aptamer capturing approach that improves the specificity and the sensitivity of enzyme detection. An aptamer recognizing the target enzyme molecule is conjugated on a magnetic bead, increasing the local concentration, and serves as an affinity probe to capture and separate minute amounts of the enzyme. The captured enzymes catalyze the subsequent conversion of fluorogenic substrate to fluorescent products, enabling a sensitive measure of the active enzyme. The feasibility of this technique is demonstrated through assays for human alpha thrombin and human neutrophil elastase (HNE), two important enzymes. Thrombin (2 fM) and 100 fM HNE can be detected. The incorporation of two binding events, substrate recognition and aptamer binding, greatly improves assay specificity. With its simplicity, this approach is applicable to biosensing and detection of disease biomarkers. PMID- 22098164 TI - Inflammatory stress exacerbates hepatic cholesterol accumulation via disrupting cellular cholesterol export. AB - BACKGROUND AND AIM: Both inflammation and cholesterol accumulation play important roles in the development of non-alcoholic fatty liver disease. This study was undertaken to investigate whether inflammation aggravated cholesterol accumulation via disrupting hepatic cholesterol export and we explored the underlying mechanisms. METHODS: We used casein injection in C57BL/6J mice, and tumor necrosis factor alpha (TNF-alpha) stimulation in human hepatoblastoma cell line (HepG2) cells to induce inflammation. Intracellular cholesterol level was examined by Oil Red O staining and quantitative analysis. Bile acid level was quantified by colorimetric analysis. (3)[H] cholesterol assay by scintillation counting was performed to evaluate the cholesterol efflux. The mRNA and protein expression was examined by real-time polymerase chain reaction and Western blot. RESULTS: Inflammation increased cholesterol accumulation in livers of C57BL/6J mice and in HepG2 cells. High-fat diet in mice and low-density lipoprotein (LDL) loading in HepG2 cells increased bile acid synthesis and cholesterol efflux, enhanced the mRNA and protein expression of liver X receptor alpha (LXRalpha), peroxisome proliferator-activated receptors (PPARalpha, gamma), cholesterol 7alpha-hydroxylase (CYP7A1) and ATP-binding cassette transporter A1 (ABCA1). However, inflammation reduced bile acid synthesis and cholesterol efflux even in high-fat-diet-fed mice and HepG2 cells in the presence of LDL loading. The enhanced effects of these genes and proteins expression due to high-fat diet and LDL loading were inhibited by inflammation both in vivo and in vitro. CONCLUSIONS: Inflammation disrupted PPAR-LXR-CYP7A1/ABCA1-mediated bile acid synthesis and cholesterol efflux resulting in exacerbated cholesterol accumulation in livers of C57BL/6J mice and HepG2 cells. PMID- 22098165 TI - Foxp3(+)CD4(+)CD25(+) regulatory T cells are increased in patients with Coxiella burnetii endocarditis. AB - Chronic Q fever, which principally manifests as endocarditis, is characterized by Coxiella burnetii persistence and an impaired cell-mediated immune response. The long-term persistence of pathogens has been associated with the expansion of regulatory T cells (Tregs), the CD4(+) T-cell subset that is characterized by the expression of CD25 and Foxp3. We investigated the presence of Tregs in patients with acute Q fever (n = 17), known to exhibit an efficient immune response, patients with Q fever endocarditis (n = 54) and controls (n = 27) by flow cytometry. The proportion of CD3(+) , CD4(+) and CD8(+) T cells was similar in controls and patients with Q fever. The percentage of CD4(+) T cells that expressed CD25 was similar in controls and patients with Q fever. The population of CD4(+) T cells that expressed both CD25 and Foxp3 was significantly (P < 0.001) increased in patients with Q fever endocarditis compared with controls. Our data suggest that the expansion of Tregs may be critical for the chronic evolution of Q fever. PMID- 22098166 TI - Chorionic villus sampling for abnormal screening compared to historical indications: prevalence of abnormal karyotypes. AB - OBJECTIVE: To determine the prevalence of abnormal karyotype results in women undergoing chorionic villus sampling (CVS) for abnormal first trimester screening compared to CVS for historical indications (advanced maternal age (AMA) or prior aneuploidy). METHODS: Retrospective cohort of all patients undergoing CVS at Oregon Health & Science University from January 2006 to June 2010. Patients were separated based on CVS indication: (1) positive ultrasound (U/S) or serum screening; or (2) AMA or prior aneuploidy with normal or no screening. Prevalence of abnormal karyotype results were compared between groups. RESULTS: Fetal karyotyping was successful in 500 of 506 CVS procedures performed. 203 CVS were performed for positive screening with 69 abnormal karyotypes (34.0%). 264 CVS were performed for historical indications with 11 abnormal karyotypes (4.2%). This difference was statistically significant (chi(2) 71.9, p < 0.001; OR 11.8 [95% CI 5.8, 24.6]). There were two age-related aneuplodies in AMA women without positive screening. 42 out of 44 AMA women diagnosed with aneuploidy (95.5%) had abnormal U/S and/or serum screening (35 U/S, 4 serum, 3 U/S and serum). CONCLUSIONS: Combined ultrasound and serum screening should be recommended to all women, including AMA women, prior to undergoing invasive testing to improve risk based counseling and minimize morbidity. PMID- 22098167 TI - Audiovisual distraction reduces pain perception during shockwave lithotripsy. AB - BACKGROUND AND PURPOSE: Lithotripsy is an established method to fragment kidney stones that can be performed without general anesthesia in the outpatient setting. Discomfort and/or noise, however, may deter some patients. It has been demonstrated that audiovisual distraction (AV) can reduce sedoanalgesic requirements and improve patient satisfaction in nonurologic settings, but to our knowledge, this has not been investigated with lithotripsy. This randomized controlled trial was designed to test the hypothesis that AV distraction can reduce perceived pain during lithotripsy. PATIENTS AND METHODS: All patients in the study received identical analgesia before a complete session of lithotripsy on a fixed-site Storz Modulith SLX F2 lithotripter. Patients were randomized to two groups: One group (n=61) received AV distraction via a wall-mounted 32" (82 cm) television with wireless headphones; the other group (n=57) received no AV distraction. The mean intensity of treatment was comparable in both groups. Patients used a visual analogue scale (0-10) to record independent pain and distress scores and a nonverbal pain score was documented by the radiographer during the procedure (0-4). RESULTS: In the group that received AV distraction, all measures of pain perception were statistically lower. The patient-reported pain score was reduced from a mean of 6.1 to 2.4 (P<0.0001), and the distress score was reduced from a mean of 4.4 to 1.0 (P=0.0001). The mean nonverbal score recorded by the radiographer was reduced from 1.5 to 0.5 (<0.0001). CONCLUSIONS: AV distraction significantly lowered patients' reported pain and distress scores. This correlated with the nonverbal scores reported by the radiographer. We conclude that AV distraction is a simple method of improving acceptance of lithotripsy and optimizing treatment. PMID- 22098168 TI - Induction of a viable-but-non-culturable state in bacteria treated with gas discharge plasma. PMID- 22098169 TI - Approximating protein flexibility through dynamic pharmacophore models: application to fatty acid amide hydrolase (FAAH). AB - A structure-based drug discovery method is described that incorporates target flexibility through the use of an ensemble of protein conformations. The approach was applied to fatty acid amide hydrolase (FAAH), a key deactivating enzyme in the endocannabinoid system. The resultant dynamic pharmacophore models are rapidly able to identify known FAAH inhibitors over drug-like decoys. Different sources of FAAH conformational ensembles were explored, with both snapshots from molecular dynamics simulations and a group of X-ray structures performing well. Results were compared to those from docking and pharmacophore models generated from a single X-ray structure. Increasing conformational sampling consistently improved the pharmacophore models, emphasizing the importance of incorporating target flexibility in structure-based drug design. PMID- 22098171 TI - Disaster risk reduction capacity assessment for precarious settlements in Guatemala City. AB - This study presents findings of an institutional capacity analysis of urban disaster risk reduction for informal settlements in the Guatemala Metropolitan Region. It uses a resource access perspective of vulnerability, actor-network theory, and qualitative data collection. The analysis reveals that there is interest in disaster risk reduction for the informal settlements; however, there is little in the way of direct financial or oversight relationships between informal settlement residents and all other actors. Respondents observed that informal settlements would probably remain inhabited; thus, there is a need for disaster risk reduction within these settlements. Disaster risk reduction capacity for informal settlements exists and can be further leveraged, as long as steps are taken to ensure appropriate access to and control of resources and oversight. Further, the nascent institutional arrangements should be strengthened through increased communication and coordination between actors, a decentralization of oversight and financial relationships, and mediation of identified resource conflicts. PMID- 22098170 TI - An alternative strategy of dismantling of the chloroplasts during leaf senescence observed in a high-yield variety of barley. AB - Changes in function and composition of the photosynthetic apparatus as well as the ultrastructure of chloroplasts in mesophyll cells were analyzed in flag leaves of the high-yield barley (Hordeum vulgare) variety cv. Lomerit during senescence under field conditions in two successive years. In contrast to previous results obtained with the elder variety cv. Carina photosystem II efficiency measured by F(v)/F(m) was found to be rather stable until a very late stage of senescence. Chlorophyll a fluorescence and P700 absorbance measurements revealed that the activities of the two photosystems declined in parallel. An increase in the chlorophyll a/b ratio at a late stage of senescence was observed to coincide with a decline in the level of the Lhcb1 apoprotein of the light harvesting complex (LHC) and the level of the corresponding transcript. Ultrastructural investigations revealed the presence of gerontoplasts that have long, single or pairwise thylakoids and lack large grana stacks. It is hypothesized that the early degradation of grana thylakoids harboring the major LHC reduced the risk of photoinhibition and might be causally related to the high yield of the barley variety cv. Lomerit. PMID- 22098172 TI - Convergent formal synthesis of (+/-)-roseophilin. AB - A facile convergent synthesis of the tricyclic core 2 of roseophilin is described, which represents the shortest route so far for the formal synthesis of roseophilin. The key step was a tandem pyrrole acylation-Nazarov cyclization reaction to form the cyclopenta[b]pyrrole moiety 4. PMID- 22098173 TI - Enhancing the effect of the nanofiber network structure on thermoresponsive wettability switching. AB - This letter reports the enhancing effects of a nanofiber network structure on stimuli-responsive wettability switching. Thermoresponsive coatings composed of nanofibers were prepared by electrospinning from thermoresponsive polymer poly(N isopropylacrylamide) (PNIPAAm). The nanofiber coatings showed a large amplitude of thermoresponsive change in the wettability from hydrophilic to hydrophobic states compared to a smooth cast film. In particular, the combination of the surface chemistry and unique topology of the electrospun nanofiber coatings enables a transition from the Wenzel state to the metastable Cassie-Baxter state with an increase in temperature and consequently an enhanced amplitude of change in the water contact angles: the apparent contact angle differences between 25 and 50 degrees C are Deltatheta*(25-50 degrees C )= 108 and 10 degrees for the nanofiber coatings with a diameter of 830 nm and a smooth cast film, respectively. The fabrication of the 3D nanofiber network structure by electrospinning from stimuli-responsive materials is a promising option for highly responsive surfaces in wettability. PMID- 22098174 TI - Synthesis of the cancer preventive peptide lunasin by lactic acid bacteria during sourdough fermentation. AB - This study aimed to exploit the potential of sourdough lactic acid bacteria to release lunasin during fermentation of cereal and nonconventional flours. The peptidase activities of a large number of sourdough lactic acid bacteria were screened using synthetic substrates. Selected lactic acid bacteria were used as sourdough starters to ferment wholemeal wheat, soybean, barley, amaranth, and rye flours. Proteinase activity during fermentation was characterized by SDS-PAGE analysis of the water-soluble extracts. Albumins having molecular masses of 18 to 22 kDa, which included the size of lunasin precursors, were markedly affected by proteolysis of lactic acid bacteria. After fermentation, lunasin from the water soluble extracts was quantified, purified, and identified through RP-HPLC and nano-LC-ESI-MS analyses. Compared to control doughs, the concentration of lunasin increased up to 2-4 times during fermentation. Lactobacillus curvatus SAL33 and Lactobacillus brevis AM7 synthesized the highest concentrations of lunasin in all the flours. Besides the presence of the entire lunasin sequence, fragments containing the immunoreactive epitope RGDDDDDDDDD were also found. This study shows that fermentation by lactic acid bacteria increased the concentration of lunasin to levels that would suggest new possibilities for the biological synthesis and for the formulation of functional foods. PMID- 22098175 TI - Academic achievement and smoking initiation in adolescence: a general growth mixture analysis. AB - AIMS: This study aims to: (i) explore the relations between smoking initiation and different profiles of academic achievement trajectories in early to mid adolescence; and (ii) to investigate whether background characteristics (gender, ethnicity, grade repetition, parental education) and proximal processes (parental practices, extra-curricular involvement) predicted class membership and smoking initiation. DESIGN: Four-year longitudinal cohort study (7th-10th grade). SETTING: Adolescents completed the questionnaires during school hours. PARTICIPANTS: At total of 741 adolescents with no history of smoking in grade 7 participating in the Montreal Adolescent Depression Development Project. MEASUREMENTS: Self-report questionnaires were used to assess predictors and previous smoking in year 1, and smoking initiation by the end of the study. Grade point average (GPA) was obtained twice yearly from school records. FINDINGS: Three academic achievement trajectories were identified and found to differ significantly in rates of smoking initiation: persistently high achievers (7.1% smoking), average achievers (15.1% smokers) and unstable low achievers (49.1% smoking). Further, results showed that general parenting practices and parental education indirectly reduced the likelihood of smoking by reducing the risk of membership in classes with lower GPA. CONCLUSIONS: Adolescents who do well in school are less likely to smoke and it may be cost-effective for smoking prevention to focus on the few (12%) easy to identify unstable low achievers who form 35% of smoking onsets. In addition, as parental support and democratic control reduced the likelihood of poor academic performance, promoting essential generic parenting skills from a young age may also prevent future onsets of smoking in adolescence. PMID- 22098176 TI - Multiple effects of Honokiol on the life cycle of hepatitis C virus. AB - BACKGROUND: Honokiol, a small active molecular compound extracted from magnolia, has recently been shown to inhibit hepatitis C virus (HCV) infection in vitro. AIMS: This study further characterized aspects of the HCV lifecycle affected by the antiviral functions of honokiol. METHODS: The influence of honokiol on HCV infection, entry, translation and replication was assessed in Huh-7.5.1 cells using cell culture-derived HCV (HCVcc), HCV pseudo-type (HCVpp) and sub-genomic replicons. RESULTS: Honokiol had strong antiviral effect against HCVcc infection at non-toxic concentrations. Combined with interferon-alpha, its inhibitory effect on HCVcc was more profound than that of ribavirin. Honokiol inhibited the cell entry of lentiviral particles pseudo-typed with glycoproteins from HCV genotypes 1a, 1b, and 2a, but not of the vesicular stomatitis virus. It had inefficient activity on HCV internal ribosome entry site (IRES)-translation at concentrations with significant anti-HCVcc effects. The expression levels of components of replication complex, NS3, NS5A and NS5B, were down-regulated by honokiol in a dose-dependent manner. It also inhibited HCV replication dose dependently in both genotypes 1b and 2a sub-genomic replicons. CONCLUSIONS: Honokiol inhibits HCV infection by targeting cell entry and replication and, only at a concentration >30 MUM, IRES-mediated translation of HCV life cycle. Based on its high therapeutic index (LD(50) /EC(90) = 5.4), honokiol may be a promising drug for the treatment of HCV infection. PMID- 22098177 TI - The influence of YMDD mutation patterns on clinical outcomes in patients with adefovir add-on lamivudine combination treatment. AB - BACKGROUND/AIM: The aim of this study was to assess the patterns of lamivudine (LAM)-resistant mutations and the influence on biochemical and virological responses to adefovir (ADV) add-on LAM combination therapy in patients with LAM resistant chronic hepatitis B (CHB). METHODS: Seventy-eight CHB patients with confirmed genotypic resistance to LAM, who initiated ADV add-on LAM combination treatment, were enrolled at our institution between April 2007 and April 2009. RESULTS: The baseline tyrosine-methionine-aspartate-aspartate (YMDD) mutation patterns were as follows: rtM204I 45 (57.7%); and rtM204V + rtM204I/V 33 (42.3%). The decrease in the mean +/- standard deviation (SD) serum log(10) HBV-DNA level did not differ between the patients carrying the rtM204I vs. rtM204IV +rtM204I/V mutations at 3, 6 and 12 months after the initiation of ADV add-on LAM combination treatment. The proportion of patients who achieved ALT normalization (<40 IU/L) 12 months after the initiation of ADV add-on LAM combination treatment were significantly higher in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations (39 [86.7%] vs. 22 [66.7%], P = 0.05). The proportion of patients in whom the log(10) HBV-DNA decreased <2 log(10) copies/ml, 6 months after the initiation of ADV add-on LAM combination treatment (non-responders), was significantly higher in patients with a rtM204V + rtM204I/V mutations than rtM204I mutation (7 [21.2%] vs. 2 [4.4%], P = 0.032). CONCLUSION: Biochemical response at 12 months from baseline was better in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations. In addition, early treatment failure was more common in patients with rtM204V+ rtM204I/V mutations than a rtM204I mutation. PMID- 22098178 TI - The frailty syndrome: a comprehensive review. AB - The frailty syndrome is defined as unintentional weight and muscle loss, exhaustion, and declines in grip strength, gait speed, and activity. Evidence with respect to the clinical definition, epidemiology, mechanisms, interactions, assessment, prevention, and treatment of frailty in the older adult is reviewed. PMID- 22098179 TI - Effectiveness of educational interventions to improve food safety practices among older adults. AB - The purpose of the study was to develop and evaluate the effectiveness of using Web-based and print materials for improving food safety practices to reduce the risk of foodborne illness among older adults. The study used a randomized controlled design, with participants assigned to an intervention group or control group. Although we observed small improvements in both groups, the difference in the changes between the two groups was nonsignificant, suggesting the educational materials did not impact participant behavior. We did, however, observe a trend improvement in one measure: the recommendation to avoid eating cold (not reheated) deli meats. The lack of program impact may be attributable to limitations of the evaluation (e.g., measurement effects) or the intervention (e.g., lack of personal contact). Based on the survey findings, improvements in older adults' food safety practices regarding reheating deli meats to steaming hot and cooking eggs until the yolks and whites are firm are needed. The current study and previous research suggest that current cohorts of older adults may be more receptive to print materials than Web-based materials. To improve retention and adoption of recommended food safety practices among older adults, future educational interventions should focus on a limited number of practices and combine print materials with personal contact. PMID- 22098181 TI - Obesity is more strongly associated with inappropriate eating behaviors than with mental health in older adults receiving congregate meals. AB - This study explored the relationships of inappropriate eating behaviors and mental health with obesity in congregate meal participants in Georgia (N = 120, mean age = 75 years, 75% female, 43% African American). Inappropriate eating behaviors were evaluated with the Three-Factor Eating Questionnaire (18 questions); mental health was assessed with the Depression Anxiety Stress Scale (21 questions); history of depression was assessed with the Behavioral Risk Factor Surveillance Survey; and height and weight were measured to calculate body mass index (BMI) and obesity (52% >= 30 kg/m(2)). In bivariate analyses, obesity was associated with cognitive restraint (rho = 0.49, p < 0.0001), uncontrolled eating (rho = 0.22; p < 0.01), emotional eating (rho = 0.32, p < 0.001), and stress (rho = 0.18, p < 0.05), but not with depression or anxiety. In multivariate regression analyses including all six eating behavior and mental health indices, only cognitive restraint and emotional eating were consistently associated with obesity (p < 0.05) when controlled for potential confounders (demographics, food insecurity, and chronic health conditions). Thus, mental health symptoms and inappropriate eating behaviors, particularly cognitive restraint and emotional eating, may be important targets for future research and intervention. Additional research is needed to better understand how cognitive restraint and emotional eating contribute to obesity in this population so that interdisciplinary research and health care teams can appropriately prevent and manage obesity in congregate meal participants. PMID- 22098180 TI - A theoretically based Behavioral Nutrition Intervention for Community Elders at high risk: the B-NICE randomized controlled clinical trial. AB - We conducted a study designed to evaluate the efficacy and feasibility of a multilevel self-management intervention to improve nutritional intake in a group of older adults receiving Medicare home health services who were at especially high risk for experiencing undernutrition. The Behavioral Nutrition Intervention for Community Elders (B-NICE) trial used a prospective randomized controlled design to determine whether individually tailored counseling focused on social and behavioral aspects of eating resulted in increased caloric intake and improved nutrition-related health outcomes in a high-risk population of older adults. The study was guided by the theoretical approaches of the Ecological Model and Social Cognitive Theory. The development and implementation of the B NICE protocol, including the theoretical framework, methodology, specific elements of the behavioral intervention, and assurances of the treatment fidelity, as well as the health policy implications of the trial results, are presented in this article. PMID- 22098186 TI - Demodex-associated bacterial proteins induce neutrophil activation. AB - BACKGROUND: Patients with rosacea demonstrate a higher density of Demodex mites in their skin than do controls. A bacterium isolated from a Demodex mite from a patient with papulopustular rosacea (PPR) was previously shown to provoke an immune response in patients with PPR or ocular rosacea, thus suggesting a possible role for bacterial proteins in the aetiology of this condition. OBJECTIVES: To examine the response of neutrophils to proteins derived from a bacterium isolated from a Demodex mite. METHODS: Bacterial cells were lysed and proteins were partially purified by AKTA fast protein liquid chromatography. Isolated neutrophils were exposed to bacterial proteins and monitored for alterations in migration, degranulation and cytokine production. RESULTS: Neutrophils exposed to proteins from Bacillus cells demonstrated increased levels of migration and elevated release of matrix metalloprotease 9, an enzyme known to degrade collagen, and cathelicidin, an antimicrobial peptide. In addition, neutrophils exposed to the bacterial proteins demonstrated elevated rates of interleukin 8 and tumour necrosis factor-alpha production. CONCLUSIONS: Proteins produced by a bacterium isolated from a Demodex mite have the ability to increase the migration, degranulation and cytokine production abilities of neutrophils. These results suggest that bacteria may play a role in the inflammatory erythema associated with rosacea. PMID- 22098187 TI - Detailed features of palisade vessels as a marker of the esophageal mucosa revealed by magnifying endoscopy with narrow band imaging. AB - The palisade vessels present at the distal end of the esophagus are considered to be a landmark of the esophagogastric junction and indispensable for diagnosis of columnar-lined esophagus on the basis of the Japanese criteria. Here we clarified the features of normal palisade vessels at the esophagogastric junction using magnifying endoscopy. We prospectively studied palisade vessels in 15 patients undergoing upper gastrointestinal endoscopy using a GIF-H260Z instrument (Olympus Medical Systems Co., Tokyo, Japan). All views of the palisade vessels were obtained at the maximum magnification power in the narrow band imaging mode. We divided the area in which palisade vessels were present into three sections: the area from the squamocolumnar junction (SCJ) to about 1 cm orad within the esophagus (Section 1); the area between sections 1 and 3 (Section 2); and the area from the upper limit of the palisade vessels to about 1 cm distal within the esophagus (Section 3). In each section, we analyzed the vessel density, caliber of the palisade vessels, and their branching pattern. The vessel density in Sections 1, 2, and 3 was 9.1 +/- 2.1, 8.0 +/- 2.6, and 3.3 +/- 1.3 per high-power field (mean +/- standard deviation [SD]), respectively, and the differences were significant between Sections 1 and 2 (P= 0.0086) and between Sections 2 and 3 (P < 0.0001). The palisade vessel caliber in Sections 1, 2, and 3 was 127.6 +/- 52.4 um, 149.6 +/- 58.6 um, and 199.5 +/- 75.1 um (mean +/- SD), respectively, and the differences between Sections 1 and 2, and between Sections 2 and 3, were significant (P < 0.0001). With regard to branching form, the frequency of branching was highest in Section 1, and the 'normal Y' shape was observed more frequently than in Sections 2 and 3. Toward the oral side, the frequency of branching diminished, and the frequency of the 'upside down Y' shape increased. The differences in branching form were significant among the three sections (P < 0.0001). These results indicate that the density of palisade vessels is highest near the SCJ, and that towards their upper limit they gradually become more confluent and show an increase of thickness. Within a limited area near the SCJ, observations of branching form suggest that palisade vessels merge abruptly on the distal side. We have demonstrated that palisade vessels are a useful marker for endoscopic recognition of the lower esophagus. PMID- 22098185 TI - Evaluation of the adverse effect of premature discontinuation of pegylated interferon alpha-2b and ribavirin treatment for chronic hepatitis C virus infection: results from Kyushu University Liver Disease Study. AB - BACKGROUND AND AIMS: Pegylated interferon (PEG-IFN) alpha-2b and ribavirin (RBV) treatment of chronic hepatitis C virus (HCV) infection is associated with a substantially elevated risk of discontinuation. The aim of this study is to evaluate the reason for premature discontinuation during PEG-IFN alpha-2b and RBV treatment due to adverse effects in patients with chronic HCV infection. METHODS: A total of 2871 Japanese patients who had chronic HCV infection treated with PEG IFN alpha-2b and RBV were screened. We prospectively investigated the reasons for premature discontinuation of treatment classified by sex and age, and analyzed the timing of discontinuation. RESULTS: Of the 2871 patients, 250 (8.7%) discontinued treatment because of adverse effects. The main reasons for premature discontinuation were neurovegetative symptoms (n = 77, 30.8%), depression-related syndrome (n = 46, 18.4%), hematologic effects (n = 41, 16.4%) and dermatologic effects (n = 27, 10.8%). The rate of discontinuation of treatment for patients aged >= 65 years was significantly higher than for patients aged < 65 years, for both men (P < 0.0001) and women (P = 0.0121). Moreover, the frequency of discontinuation due to neurovegetative symptoms, depression-related syndrome, and hematologic effects for men aged >= 65 years was significantly higher than for those aged < 65 years (P = 0.0001, P = 0.0016, and P = 0.0170, respectively), but not for women. CONCLUSION: Premature discontinuation due to the adverse effects of PEG-IFN alpha-2b and RBV treatment by patients with chronic HCV infection is mainly due to neuropsychiatric symptoms and is more common for older than for younger patients. PMID- 22098188 TI - Kinematic and kinetic analyses of novice running in dress shoes and running shoes. AB - The purpose of the study was to investigate how novice runners adjust their lower extremities in heel-toe running while they wear dress shoes and running shoes. Ten novice male runners repeatedly ran across a force plate at 4 m/s in each type of shoes. Joint kinematics and kinetics, vertical ground reaction force, and utilized coefficient of friction during the stance phase were quantified. The results obtained showed no differences in impact peaks, stance time, stride length and joint kinematics. However, dorsiflexion moment was significantly greater with dress shoes (407 Nm) compared to that with running shoes (304 Nm; p<0.05). Compared to the runners in running shoes (0.23), the runners in dress shoes (0.20) achieved a significantly lower utilized coefficient of friction ( p<0.05). When running in dress shoes, novice runners tended to use better a dorsiflexion moment than when running in running shoes. This adaptation appears to minimize the chances of slipping at the moment of heel strike. PMID- 22098190 TI - The molecular pathogenesis of corticotroph tumours. AB - BACKGROUND: The pathogenesis of tumour formation in the anterior pituitary including adrenocorticotropic hormone (ACTH)-secreting tumours has been intensively studied, but the causative mechanisms involved in pituitary cell transformation and tumourigenesis remain unclear. MATERIALS AND METHODS: We searched PubMed on any paper related with molecular pathology of pituitary corticotroph adenomas and have included to this review all relevant references published up to June 2011. RESULTS: Current studies increased our knowledge on the genetic basis of McCune-Albright syndrome (MAS), multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), pituitary adenoma predisposition syndromes and tuberous sclerosis, but they have performed little to elucidate the causes of sporadic pituitary tumours including Cushing disease. DISCUSSION: The aim of this review was to focus on the most recently published advances in the molecular pathology of corticotroph adenomas, which are presented in the context of changes seen in all types of pituitary adenomas, as well as in terms of corticotrophin releasing hormone/ACTH/cortisol-specific pathways. CONCLUSIONS: We would expect that over the next 5 years, more detailed analysis of inter-cellular communication pathways between pituitary cells, including the cadherins and integrins, and their interactions with other signalling pathways such as the beta catenin cascade will help elucidate what exactly goes awry in the formation of a benign corticotroph adenoma. This should in turn predict novel forms of pharmacological tumour control. PMID- 22098189 TI - NADPH oxidase 1-mediated oxidative stress leads to dopamine neuron death in Parkinson's disease. AB - AIM: Oxidative stress has long been considered as a major contributing factor in the pathogenesis of Parkinson's disease. However, molecular sources for reactive oxygen species in Parkinson's disease have not been clearly elucidated. Herein, we sought to investigate whether a superoxide-producing NADPH oxidases (NOXs) are implicated in oxidative stress-mediated dopaminergic neuronal degeneration. RESULTS: Expression of various Nox isoforms and cytoplasmic components were investigated in N27, rat dopaminergic cells. While most of Nox isoforms were constitutively expressed, Nox1 expression was significantly increased after treatment with 6-hydroxydopamine. Rac1, a key regulator in the Nox1 system, was also activated. Striatal injection of 6-hydroxydopamine increased Nox1 expression in dopaminergic neurons in the rat substantia nigra. Interestingly, it was localized into the nucleus, and immunostaining for DNA oxidative stress marker, 8 oxo-dG, was increased. Nox1 expression was also found in the nucleus of dopaminergic neurons in the substantia nigra of Parkinson's disease patients. Adeno-associated virus-mediated Nox1 knockdown or Rac1 inhibition reduced 6 hydroxydopamine-induced oxidative DNA damage and dopaminergic neuronal degeneration significantly. INNOVATION: Nox1/Rac1 could serve as a potential therapeutic target for Parkinson's disease. CONCLUSION: We provide evidence that dopaminergic neurons are equipped with the Nox1/Rac1 superoxide-generating system. Stress-induced Nox1/Rac1 activation causes oxidative DNA damage and neurodegeneration. Reduced dopaminergic neuronal death achieved by targeting Nox1/Rac1, emphasizes the impact of oxidative stress caused by this system on the pathogenesis and therapy in Parkinson's disease. PMID- 22098191 TI - Crystal structure of 6-SST/6-SFT from Pachysandra terminalis, a plant fructan biosynthesizing enzyme in complex with its acceptor substrate 6-kestose. AB - Fructans play important roles as reserve carbohydrates and stress protectants in plants, and additionally serve as prebiotics with emerging antioxidant properties. Various fructan types are synthesized by an array of plant fructosyltransferases belonging to family 32 of the glycoside hydrolases (GH32), clustering together with GH68 in Clan-J. Here, the 3D structure of a plant fructosyltransferase from a native source, the Pachysandra terminalis 6-SST/6-SFT (Pt6-SST/6-SFT), is reported. In addition to its 1-SST (1-kestose-forming) and hydrolytic side activities, the enzyme uses sucrose to create graminan- and levan type fructans, which are probably associated with cold tolerance in this species. Furthermore, a Pt6-SST/6-SFT complex with 6-kestose was generated, representing a genuine acceptor binding modus at the +1, +2 and +3 subsites in the active site. The enzyme shows a unique configuration in the vicinity of its active site, including a unique D/Q couple located at the +1 subsite that plays a dual role in donor and acceptor substrate binding. Furthermore, it shows a unique orientation of some hydrophobic residues, probably contributing to its specific functionality. A model is presented showing formation of a beta(2-6) fructosyl linkage on 6-kestose to create 6,6-nystose, a mechanism that differs from the creation of a beta(2-1) fructosyl linkage on sucrose to produce 1-kestose. The structures shed light on the evolution of plant fructosyltransferases from their vacuolar invertase ancestors, and contribute to further understanding of the complex structure-function relationships within plant GH32 members. PMID- 22098192 TI - Meta-analysis for evaluating the accuracy of endoscopy with narrow band imaging in detecting colorectal adenomas. AB - BACKGROUND AND AIM: The aim of this study was to determine whether the use of the narrow band imaging (NBI) system could enhance the accuracy of adenoma detection during an endoscopic examination of the colon and rectum. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched along with a hand search of abstracts from relevant conferences up to June 2011. The rates of adenoma and flat adenoma detection, and withdrawal time were analyzed using Review Manager 4.2. RESULTS: A total of 3049 subjects in eight trials were included. Meta analysis revealed that there was no statistically significant difference in the rates of adenoma detection between the NBI group and the white light colonoscopy group (pooled relative risk [RR]: 1.09, 95% confidence interval [CI]: 1.00-1.19, P = 0.05). However, after exclusion of high-definition television modalities, the rate of adenoma detection by NBI was significantly higher than that by white light, particularly for patients with one adenoma (pooled RR 1.36, 95%CI 1.07 1.71, P = 0.02). Endoscopy with the NBI system significantly increased the rate of flat adenoma detection (pooled RR 1.96, 95%CI 1.09-3.52, P = 0.02). However, endoscopy with NBI had longer withdrawal time than that with white light (pooled weighted mean difference: 0.90, 95%CI: 0.38-1.42, P = 0.0006). CONCLUSIONS: Endoscopy with NBI seems to improve the detection of flat adenomas, particularly with high-definition technology, but prolongs the withdrawal time. These results indicate that endoscopy routinely using the NBI system for the surveillance of adenomas may be recommended after the technique is further modified. PMID- 22098193 TI - Adsorption of water molecules on selected charged sodium-chloride clusters. AB - The adsorption of water molecules (H(2)O) on sodium chloride cluster cations and anions was studied at 298 K over a mass range of 100-1200 amu using a custom built laser desorption ionization reactor and mass spectrometer. Under the conditions used, the cations Na(3)Cl(2)(+) and Na(4)Cl(3)(+) bind up to three water molecules, whereas the larger cations, Na(5)Cl(4)(+) to Na(19)Cl(18)(+), formed hydrates with one or two only. The overall trend is a decrease in hydration with increasing cluster size, with an abrupt drop occurring at the closed-shell Na(14)Cl(13)(+). As compared to the cluster cations, the cluster anions showed almost no adsorption. Among smaller clusters, a weak adsorption of one water molecule was observed for the cluster anions Na(6)Cl(7)(-) and Na(7)Cl(8)(-). In the higher mass region, a substantial adsorption of one water molecule was observed for Na(14)Cl(15)(-). Density functional theory (DFT) computations were carried out for the adsorption of one molecule of H(2)O on the cations Na(n)Cl(n-1)(+), for n = 2-8, and the anions Na(n)Cl(n+1)(-), for n = 1 7. For each ion, the structure of the hydrate, the hydration energy, and the standard-state enthalpy, entropy, and Gibbs energy of hydration at 298 K were computed. In addition, it was useful to compute the distortion energy, defined as the electronic energy lost due to weakening of the Na-Cl bonds upon adsorption of H(2)O. The results show that strong adsorption of a H(2)O molecule occurs for the linear cations only at an end Na ion and for the nonlinear cations only at a corner Na ion bonded to two Cl ions. An unexpected result of the theoretical investigation for the anions is that certain low-energy isomers of Na(6)Cl(7)(-) and Na(7)Cl(8)(-) bind H(2)O strongly enough to produce the observed weak adsorption. The possible implications of these results for the initial hydration of extended NaCl surfaces are discussed. PMID- 22098194 TI - Traumatic brain injury or decompression. PMID- 22098196 TI - An episode of severely suppressed electrocerebral activity recorded by electroencephalography during endoscopic resection of a colloid cyst. AB - Intraoperative neuromonitoring utilizing electroencephalography (EEG) is rarely performed during neuroendoscopy. The authors present a case in which this monitoring modality was used for a patient with a colloid cyst in preparation for an open craniotomy should an endoscopic approach fail. In this case, EEG serendipitously captured near-complete cessation of electrocerebral activity that occurred during intraventricular irrigation in response to ventricular collapse and resulted in no postoperative deficits. To the authors' knowledge, this is the first reported case of severe suppression of electrical activity captured by EEG during neuroendoscopy. Although they describe a transient phenomenon that resulted in no residual cognitive or neurological deficits, the importance of cautious introduction of ventricular irrigation, the need to carefully monitor intracranial pressure during neuroendoscopic procedures, and the need to pay close attention to irrigation temperature and composition should not be underestimated. Additional studies regarding the utility of EEG in alerting neurosurgeons to adverse electrical cerebral activity during neuroendoscopy are warranted. PMID- 22098195 TI - A multicenter pilot study of subcallosal cingulate area deep brain stimulation for treatment-resistant depression. AB - OBJECT: Deep brain stimulation (DBS) has been recently investigated as a treatment for major depression. One of the proposed targets for this application is the subcallosal cingulate gyrus (SCG). To date, promising results after SCG DBS have been reported by a single center. In the present study the authors investigated whether these findings may be replicated at different institutions. They conducted a 3-center prospective open-label trial of SCG DBS for 12 months in patients with treatment-resistant depression. METHODS: Twenty-one patients underwent implantation of bilateral SCG electrodes. The authors examined the reduction in Hamilton Rating Scale for Depression (HRSD-17) score from baseline (RESP50). RESULTS: Patients treated with SCG DBS had an RESP50 of 57% at 1 month, 48% at 6 months, and 29% at 12 months. The response rate after 12 months of DBS, however, increased to 62% when defined as a reduction in the baseline HRSD-17 of 40% or more. Reductions in depressive symptomatology were associated with amelioration in disease severity in patients who responded to surgery. CONCLUSIONS: Overall, findings from this study corroborate the results of previous reports showing that outcome of SCG DBS may be replicated across centers. PMID- 22098197 TI - Ischemia. PMID- 22098198 TI - The constant flow ventricular infusion test: a simple and useful study in the diagnosis of third ventriculostomy failure. AB - OBJECT: The evaluation of third ventriculostomy function in hydrocephalic patients is challenging. The utility of the constant flow infusion test in predicting response to shunt insertion in normal-pressure hydrocephalus, as well as in identifying shunt malfunction, has been previously demonstrated. The object of this study was to evaluate its usefulness in determining whether a revision CSF diversion procedure was indicated in patients presenting with recurring symptoms and persisting ventriculomegaly after endoscopic third ventriculostomy (ETV). METHODS: The authors conducted a prospective study of all patients who, after undergoing ETV at their institution, presented postoperatively with recurring symptoms and persisting ventriculomegaly. RESULTS: Forty-six patients (mean age 40.7 years, including 11 patients younger than 18 years) underwent 56 constant flow ventricular infusion tests (VITs) at a mean of 24.7 months post ETV. Thirty-three patients with resistance to CSF outflow (R(out)) less than 13 mm Hg/ml/min underwent follow-up (median 17 months) and experienced resolution of symptoms. In 10 episodes R(out) was greater than 13 mm Hg/ml/min; the patients in these cases underwent revisional CSF diversion. Two patients demonstrated high and frequent B (slow) waves despite a low R(out); these patients also underwent successful revisions. Patients who improved after surgery had increased B wave activity in the plateau phase of the VIT (p = 0.01). Thirty-four patients underwent MR imaging at the same time; 4 had high R(out) despite evidence of flow across the stoma. These 4 patients underwent surgery and experienced resolution of symptoms. Of 9 patients without flow, R(out) was less than 13 mm Hg/ml/min in 4; these patients were successfully treated conservatively. CONCLUSIONS: The VIT is a useful and safe adjunct to clinical and MR imaging evaluation when ETV failure is suspected. PMID- 22098199 TI - Deep brain stimulation and depression. PMID- 22098200 TI - Percutaneous biopsy of lesions in the cavernous sinus region through the foramen ovale: diagnostic accuracy and limits in 50 patients. AB - OBJECT: The cavernous sinus and surrounding regions-specifically the Meckel cave, posterior sector of the cavernous sinus itself, and the upper part of the petroclival region-are the location of a large variety of lesions that require individual consideration regarding treatment strategy. These regions may be reached for biopsy by a percutaneous needle inserted through the foramen ovale. The aim of this retrospective study was to evaluate the diagnostic accuracy of percutaneous biopsy in a consecutive series of 50 patients referred for surgery between 1991 and 2010. METHODS: Seven biopsies (14%) were unproductive and 43 (86%) were productive, among which 28 lesions subsequently underwent histopathological examination during a second (open) surgery. To evaluate the diagnostic accuracy of the procedure, results from surgery were compared with those from the biopsy. RESULTS: Sensitivity of the percutaneous biopsy was 0.83 (95% CI 0.52-0.98), specificity was 1 (95% CI 0.79-1), and kappa coefficient was 0.81. CONCLUSIONS: Because of its valuable diagnostic accuracy, percutaneous biopsy of the cavernous sinus and surrounding regions should be performed in patients with parasellar masses when neuroimaging does not provide sufficient information of a histopathological nature. This procedure would enable patients to obtain the most appropriate therapy, such as resective surgery, corticosteroids, chemotherapy, radiotherapy, or radiosurgery. PMID- 22098201 TI - Deep brain stimulation interruption and suicidality. PMID- 22098202 TI - Craniovertebral junction abnormalities with hindbrain herniation and syringomyelia: regression of syringomyelia after removal of ventral craniovertebral junction compression. AB - OBJECT: Hindbrain herniation syndrome, or Chiari malformation Type I (CM-I), occurs frequently with craniovertebral junction (CVJ) abnormalities when there is reduction in the posterior fossa volume. Syringomyelia is often present. Posterior fossa dorsal decompression (PFDD) is typically performed but has adverse results when ventral bone abnormality exists. This paper presents the results of a prospective study on CVJ abnormalities in patients with CM-I and syringomyelia. METHODS: Between 1984 and 2008 (the MR imaging era), 298 patients with CVJ abnormalities and CM-I underwent ventral cervicomedullary decompression. Eighty-four patients had associated syringomyelia (15 with secondary invagination and 69 with primary basilar invagination, os odontoideum, or malunion of fractures). Of these 84 patients with CVJ abnormalities, CM-I, and syringomyelia, 46 had previously undergone PFDD, and 28 had previously undergone PFDD combined with fusion procedures or shunt placements. Of the 84 patients, a cervicothoracic syrinx was observed in 57, thoracic syrinx in 14, and holocord syrinx in 13. Studies included CT, MR imaging, and cine flow studies. All 298 patients who underwent ventral CVJ decompression had irreducible or partially reducible pathology. All 84 with syringomyelia showed brainstem dysfunction, lower cranial nerve symptoms, or myelopathy. RESULTS: Brainstem signs improved in 66 of the 84 patients, myelopathy improved in 58, and syringomyelia regressed in 64. CONCLUSIONS: Neurological improvement and syringomyelia resolution can occur using only ventral cervicomedullary junction decompression in patients with basilar invagination and basilar impression. This is likely due to the relief of neural encroachment and reestablishment of CSF pathways. PMID- 22098204 TI - Stereochemically consistent reaction mapping and identification of multiple reaction mechanisms through integer linear optimization. AB - Reaction mappings are of fundamental importance to researchers studying the mechanisms of chemical reactions and analyzing biochemical pathways. We have developed an automated method based on integer linear optimization, ILP, to identify optimal reaction mappings that minimize the number of bond changes. An alternate objective function is also proposed that minimizes the number of bond order changes. In contrast to previous approaches, our method produces mappings that respect stereochemistry. We also show how to locate multiple reaction mappings efficiently and determine which of those mappings correspond to distinct reaction mechanisms by automatically detecting molecular symmetries. We demonstrate our techniques through a number of computational studies on the GRI Mech, KEGG LIGAND, and BioPath databases. The computational studies indicate that 99% of the 8078 reactions tested can be addressed within 1 CPU hour. The proposed framework has been incorporated into the Web tool DREAM ( http://selene.princeton.edu/dream/ ), which is freely available to the scientific community. PMID- 22098205 TI - Acquired cytochrome C oxidase impairment in apheresis platelets during storage: a possible mechanism for depletion of metabolic adenosine triphosphate. AB - BACKGROUND: Intracellular adenosine triphosphate (ATP) levels decline significantly during storage of platelet (PLT) products, in part due to PLT degranulation. However, metabolic ATP stores also become depleted during storage through an unclear mechanism. Since both anaerobic glycolysis and oxidative phosphorylation are important for PLT ATP production, it is possible that the reduction in metabolic ATP reflects impaired oxidative phosphorylation. To assess this, we evaluated the kinetic activity and protein expression of cytochrome C oxidase (CcOX) in stored apheresis PLTs. STUDY DESIGN AND METHODS: Apheresis PLTs were collected and stored with agitation at 22 +/- 2 degrees C for 7 days. In vitro measurements of PLT metabolic state, function, and activation were performed on Days 0, 2, 4, and 7 of storage. Total PLT ATP content, steady-state CcOX kinetic activity, and protein immunoblotting for CcOX Subunits I and IV were also performed using isolated PLT mitochondria from simultaneously collected samples. RESULTS: Intra-PLT ATP and steady-state PLT CcOX activity declined significantly and in a progressive manner throughout storage while steady-state levels of CcOX I and IV protein remained unchanged. Time-dependent decline in CcOX activity correlated with progressive ATP depletion over time. CONCLUSION: During storage of apheresis PLTs for 7 days, the parallel decline in CcOX function and intra-PLT ATP suggests development of an acquired impairment in PLT oxidative phosphorylation associated with perturbed ATP homeostasis in stored PLTs. PMID- 22098203 TI - Comparison of induced hypertension, fluid bolus, and blood transfusion to augment cerebral oxygen delivery after subarachnoid hemorrhage. AB - OBJECT: Critical reductions in oxygen delivery (DO(2)) underlie the development of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). If DO(2) is not promptly restored, then irreversible injury (that is, cerebral infarction) may result. Hemodynamic therapies for DCI (that is, induced hypertension [IH] and hypervolemia) aim to improve DO(2) by raising cerebral blood flow (CBF). Red blood cell (RBC) transfusion may be an alternate strategy that augments DO(2) by improving arterial O(2) content. The authors compared the relative ability of these 3 interventions to improve cerebral DO(2), specifically their ability to restore DO(2) to regions where it is impaired. METHODS: The authors compared 3 prospective physiological studies in which PET imaging was used to measure global and regional CBF and DO(2) before and after the following treatments: 1) fluid bolus of 15 ml/kg normal saline (9 patients); 2) raising mean arterial pressure 25% (12 patients); and 3) transfusing 1 U of RBCs (17 patients) in 38 individuals with aneurysmal SAH at risk for DCI. Response between groups in regions with low DO(2) (< 4.5 ml/100 g/min) was compared using repeated-measures ANOVA. RESULTS: Groups were similar except that the fluid bolus cohort had more patients with symptoms of DCI and lower baseline CBF. Global CBF or DO(2) did not rise significantly after any of the interventions, except after transfusion in patients with hemoglobin levels < 9 g/dl. All 3 treatments improved CBF and DO(2) to regions with impaired baseline DO(2), with a greater improvement after transfusion (23%) than hypertension (14%) or volume loading (10%); p < 0.001. Transfusion also resulted in a nonsignificantly greater (47%) reduction in the number of brain regions with low DO(2) when compared with fluid bolus (7%) and hypertension (12%) (p = 0.33). CONCLUSIONS: The IH, fluid bolus, and blood transfusion interventions all improve DO(2) to vulnerable brain regions at risk for ischemia after SAH. Transfusion appeared to provide a physiological benefit at least comparable to IH, especially among patients with anemia, but transfusion is associated with risks. The clinical significance of these findings remains to be established in controlled clinical trials. PMID- 22098206 TI - The living environment and children's fears following the Indonesian tsunami. AB - The tsunami that struck South-east Asia on 26 December 2004 left more than 500,000 people in Aceh, Indonesia, homeless and displaced to temporary barracks and other communities. This study examines the associations between prolonged habitation in barracks and the nature of fears reported by school-age children and adolescents. In mid-2007, 30 months after the tsunami, the authors interviewed 155 child and parent dyads. Logistic regression analysis was used to compare the fears reported by children and adolescents living in barracks with those reported by their peers who were living in villages. After adjusting for demographic factors and tsunami exposure, the data reveals that children and adolescents living in barracks were three times more likely than those living in villages to report tsunami-related fears. The study demonstrates that continued residence in barracks 30 months after the tsunami is associated with higher rates of reporting tsunami-related fears, suggesting that barracks habitation has had a significant impact on the psychological experience of children and adolescents since the tsunami. PMID- 22098207 TI - A large asymptomatic hepatic mass. PMID- 22098208 TI - Detection of acylated homoserine lactones produced by Vibrio spp. and related species isolated from water and aquatic organisms. AB - AIMS: To assess the diversity in production of acylated homoserine lactones (AHLs) among Vibrio spp and related species. METHODS AND RESULTS: A total of 106 isolates, with representatives of 28 Vibrio spp and related species, were investigated for the production of AHLs. For this, a rapid method for the screening of AHLs was developed based on the use of bacterial biosensors using a double-layer microplate assay. At least one bacterial biosensor was activated in 20 species, Agrobacterium tumefaciens being the most frequently activated biosensor. One isolate of Vibrio anguillarum, Vibrio rotiferianus and Vibrio metschnikovii activated the Chromobacterium violaceum biosensor, which is not common among the Vibrionaceae family. For those species with more than one isolate, the biosensor activation profile was the same except for two species, V. anguillarum and V. metschnikovii, which varied among the different isolates. CONCLUSIONS: AHL production was observed in the majority of the studied species, with a diverse biosensor activation profile. SIGNIFICANCE AND IMPACT OF THE STUDY: The high diversity in AHL production is in consistence with the high diversity in ecological niches of the Vibrionaceae family. The absence of AHL detection in eight species warrants further work on their quorum-sensing systems. PMID- 22098209 TI - Assessment in rural health professional education. PMID- 22098210 TI - Urban-rural influences on suicidality: gaps in the existing literature and recommendations for future research. AB - Suicide is a major public health issue of particular concern among rural populations, which experience a consistently higher suicide rate than urban areas. Although extensive research efforts have been directed towards understanding suicidality and related factors, there is a continued lack of clinically useful factors to target preventive measures, particularly among some regional and demographic groups. This suggests limitations in the conceptualisation of this important construct. A review of the literature was undertaken, using a snowballing and saturation approach. Literature was considered relevant if it addressed the research question 'what are the current limitations in research on urban/rural influences on suicidality?' Findings were used to develop a set of guidelines to inform future research. A number of gaps in existing research relevant to limitations in rural suicide research were identified: inconsistencies in terminology; a focus on high-end suicidal behaviours; a disproportionate focus on urban populations; a dominance of cross sectional research; and a high use of clinical samples. These limitations are discussed in terms of their implications for rural suicidality, and are used to support the development of recommendations for future research, with a focus on encouraging consistency and standardisation. A number of limitations can be identified in existing research on suicide. Targeting these specific areas can be an important step in addressing the current gaps in knowledge relating to rural suicide prevention. PMID- 22098211 TI - Performance pressure: simulated patients and high-stakes examinations in a regional clinical school. AB - OBJECTIVE: To investigate the effects and challenges of being a simulated patient (SP) in a high-stakes clinical examination context in a regional setting. DESIGN: Mixed methods, using a written survey, focus groups, and a retrospective postal survey. SETTING: A university clinical school in a Victorian regional city. PARTICIPANTS: Nineteen SP volunteers (from an existing database of 55 people) who had been involved in mid-year, summative Objective Structured Clinical Examination (OSCE) role-play performances. MAIN OUTCOME MEASURES: Challenges of the OSCE role-play experience and the reported effects on SPs. The implications of these factors have an impact on the sustainability of SP programs in regional settings. RESULTS: Physical and emotional effects like exhaustion were reported, as well as empathy and concern for the medical students. The retrospective postal survey indicated that the SPs had no long-term negative effects from their high stakes examination experiences. Participants also reported that a level of decision making and improvisation was needed in the performance of their OSCE role plays. CONCLUSIONS: Our study reveals the complexity and demands on SPs in performing in high-stakes clinical examinations. The results highlight that SP roles involve more than the transfer of scripted information. SPs should be considered as members of the examination team when preparing and implementing high-stakes examinations to assist in maintaining standardised performance during and across OSCE role plays. Relationships between SPs and educational institutes need to be nurtured to ensure that the ability to continue high-stakes OSCEs in a regional setting is maintained. PMID- 22098212 TI - Factors influencing the selection of rural practice locations for early career pharmacists in Victoria. AB - OBJECTIVE: To identify factors influencing the choice of practice location for early career pharmacists working and living in Victoria. DESIGN: Survey. SETTING: Victorian pharmacies. PARTICIPANTS: Pharmacists living in Victoria in April 2009, who had registered with the Pharmacy Board of Victoria after 1 October 2004, stratified into major city and rural areas. MAIN OUTCOME MEASURES: Questionnaire responses analysed via descriptive statistics, chi-square and direct logistic regression. RESULTS: Early career pharmacists were more likely to practice in a rural location if they had undertaken a rural internship, had a spouse or partner with a non-metropolitan background and were not practicing in a hospital pharmacy. Pharmacists who had lived in a rural area during their childhood and had studied pharmacy at a rural university were four times more likely to have undertaken a rural internship than those that studied at a major city university. CONCLUSIONS: The strongest indicator for future practice location was a pharmacist's internship location. Childhood location and pharmacy education location were indicators of internship location. Pharmacists with a rural childhood location, especially those who study at rural universities, are more likely to work in rural areas. PMID- 22098213 TI - Travelling all over the countryside: travel-related burden and financial difficulties reported by cancer patients in New South Wales and Victoria. AB - OBJECTIVE: To describe travel burden and travel-related financial burden experienced by cancer patients over the first year after diagnosis. DESIGN, SETTING, PARTICIPANTS: Population-based longitudinal cohort of recent adult cancer patients diagnosed with the eight most incident cancers recruited from New South Wales and Victorian Cancer Registries. Self-report survey data were collected at 6 and 12 months after diagnosis from 1410 participants (city: n = 890; regional/remote: n = 520). MAIN OUTCOME MEASURES: Travel time to cancer treatment, living away from home for treatment, travel-related treatment decisions, extent of financial issues, unmet need for financial help. RESULTS: During the first 12 months after diagnosis, outer regional/remote residents had the greatest travel burden; 61% (n = 79) travelled at least 2 hours one way to receive treatment, and 49% (n = 66) lived away from home to receive treatment. Strongest associates of travel burden were living in regional/remote areas (odds ratio (OR) = 18.9-135.7), having received surgery (OR = 6.7) or radiotherapy (OR = 3.6). Between 6 and 12 months after diagnosis, 2% (n = 24) of patients declined cancer treatment because of the time it would take to get to treatment. Patients who travelled more than 2 hours or lived away for treatment reported significantly greater financial difficulties (38%; 40%) than those who did not (12%; 14%), even after adjusting for covariates. CONCLUSIONS: Travel burden is greatest for rural patients, and is associated with greater financial burden. Appropriate and adequate provision of travel and accommodation assistance schemes remains paramount to achieving equitable delivery of cancer services. PMID- 22098214 TI - Rural maternity care and health policy: parents' experiences. AB - OBJECTIVE: To explore rural residents' experiences of access to maternity care with consideration of the policy context. DESIGN: This paper describes findings from focus groups with parents which formed part of case study data from a larger study. SETTING: Four north Queensland rural towns. PARTICIPANTS: Thirty-three parents living in one of the four rural towns. MAIN OUTCOME MEASURES: Identifying prevalent themes in case studies regarding rural parents' expectations and experiences in accessing maternity care. RESULTS: Parents desired a local, safe and consistent maternity service. Removing or downgrading rural services introduced new barriers to care for rural residents: (i) increased financial costs; (ii) family issues; and (iii) safety concerns. CONCLUSIONS: Although concerns about rural residents' health status and health care access have received significant policy attention for over a decade, many of the problems which prompted these policy initiatives remain today. Current policy approaches should be re-evaluated in order to improve rural Australians' access to vital health services such as maternity care. PMID- 22098215 TI - Young mothers' lived experiences prior to becoming pregnant in rural Victoria: a phenomenological study. AB - OBJECTIVE: To explore the lived experiences and social context prior to becoming pregnant, of women who became mothers during adolescence in rural Victoria. DESIGN: Qualitative interpretive phenomenological study using semistructured interviews. SETTING: Rural community in North East Victoria, Australia. PARTICIPANTS: Four rural women who gave birth to a child between the ages of 15 and 19. RESULTS: Five themes emerged from the data as being essential to the participants' experiences prior to pregnancy. These included feeling isolated; life change: transition into adulthood; support and understanding in sexual relationships; feeling dissatisfied; and overcoming adversity. Participants' provided practical recommendations to improve life for young people in rural areas through reflecting on their own experiences. CONCLUSION: These findings highlight the complex nature of rural young women's experiences leading up to pregnancy and suggest that early motherhood might be largely reflective of the social environment in which one lives prior to pregnancy. Providing somewhere safe to go, organised and appropriate social activities and increasing access to health services were identified as being pertinent to improving experiences for rural young people prior to pregnancy. Health professionals should consider the importance of supporting young women through non-judgemental, approachable and accessible services. PMID- 22098216 TI - Asian migrants' lived experience and acculturation to Western health care in rural Tasmania. AB - OBJECTIVES: The study was designed to explore the lived experience of Asian migrants' health care-seeking behaviour in Tasmania, to discern the acculturation process by which Asian migrants are enabled to use the health system and to identify strategies, which assist migrants to understand and use the health system better. METHODS: Qualitative research was adopted. Semistructured interviews were conducted with 36 Asian migrants residing in North, South and North West Tasmania, which were recruited through purposive sampling. RESULTS: Six main themes emerged from the interviews: the acculturation process, interactions with the health care system, access issues, culturally appropriate health care, positive health care in Tasmania and suggestions for improving health care. CONCLUSIONS: The findings indicated that Asian migrants' views affected their health care-seeking behaviours because of the lack of information, poor communication, limited access and choices in Tasmania. Interestingly, those married to local Tasmanians had the shortest trajectory to health system acculturation. The study recommended developing health and well-being for Asian migrants by increasing access to information regarding navigating the health system and improving access to and awareness of language services. In addition, ensuring adequate, appropriately written, culturally specific and congruent information should be available to assist migrants' transition into a new health care system. Lastly, greater cultural awareness within the health profession to meet the needs of culturally specific individuals and communities is required when they seek care. PMID- 22098217 TI - Developing a sustainable model of rural cancer care: the Western Australian Cancer Network project. AB - PROBLEM: Cancer-related mortality is higher in rural areas than in urban centres. One of the contributing factors is limited access to treatment options in rural areas. DESIGN: An evaluation of the effectiveness of the Western Australian Cancer Network (CanNET WA) pilot project was undertaken using qualitative methods and document analysis. SETTING: CanNET WA was established in the Great Southern region of Western Australia. KEY MEASURES FOR IMPROVEMENT: Three measures were assessed: impact of the CanNET WA on consumers, care providers and changes to systems and processes. STRATEGIES FOR CHANGE: CanNET WA comprised a number of initiatives that together led to an improvement in cancer care. These included a multidisciplinary cancer team, improved access to visiting medical specialists, formal links with tertiary cancer centres, increased primary health involvement in cancer care and increased education regarding cancer care for local health care providers. EFFECTS OF CHANGE: Changes in the three key outcome measures were reported. Consumers had greater choice of treatment options and had more involvement in decision making. Health professionals reported improvements in care coordination and in peer support related to the new multidisciplinary cancer care team, and improved links with tertiary cancer centres in Perth. Systemic changes included mapping of referral pathways and tumour-specific care pathways. LESSONS LEARNT: CanNET WA has demonstrated the need for coordinated cancer care for rural people that offers care locally whenever possible. The success of the project paved the way for the rollout of the CanNET WA concept into other regional areas of Western Australia. PMID- 22098218 TI - Re It's not just about the HbA1c. PMID- 22098219 TI - Support, incentives and evidence needed to improve oral health in rural areas. PMID- 22098220 TI - Education for remote and isolated practice. PMID- 22098222 TI - Facile preparation of graphene-copper nanoparticle composite by in situ chemical reduction for electrochemical sensing of carbohydrates. AB - A novel graphene-copper nanoparticle composite was prepared by the in situ chemical reduction of a mixture containing graphene oxide and copper(II) ions using potassium borohydride as a reductant. It was mixed with paraffin oil and packed into one end of a fused capillary to fabricate microdisc electrodes for sensing carbohydrates. The morphology and structure of the graphene-copper nanoparticle composite were investigated by scanning electron microscopy, X-ray diffraction, and Fourier transform-infrared spectroscopy. The results indicated that copper nanoparticles with an average diameter of 20.8 nm were successfully deposited on graphene nanosheets to form a well interconnected hybrid network. The analytical performance of these unique graphene-copper nanoparticle composite paste electrodes was demonstrated by sensing five carbohydrates in combination with cyclic voltammetry and capillary electrophoresis (CE). The advantages of the composite detectors include higher sensitivity, satisfactory stability, surface renewability, bulk modification, and low expense of fabrication. They should find applications in microchip CE, flowing-injection analysis, and other microfluidic analysis systems. PMID- 22098223 TI - Heat-killed Lactobacillus gasseri TMC0356 protects mice against influenza virus infection by stimulating gut and respiratory immune responses. AB - This study investigated whether heat-killed Lactobacillus protects host animal against influenza virus infection and stimulates their immunity. Heat-killed Lactobacillus gasseri TMC0356 was orally administered to BALB/c mice for 19 days; the mice were intranasally infected with Flu A/PR/8/34 (H1N1) on day 14, and clinical symptoms were monitored. After 6 days, the mice were sacrificed, and pulmonary virus titres were determined. Splenic activation of natural killer (NK) cells and the mRNA expression of cytokines and other immune molecules in the lung and Peyer's patch (PP) were analysed. Clinical symptom scores of mice orally fed TMC0356 ameliorated significantly (P < 0.01); their pulmonary virus titres decreased significantly compared with those of control mice (P < 0.05); their mRNA expression of interleukin (IL)-12, IL-15 and IL-21 in PP and the pulmonary mRNA expression of IFN-gamma, TNF, IL-12a, IL-12rbl, IL-2rb and perforin 1 increased significantly (P < 0.05). Oral administration of heat-killed lactobacilli may protect against influenza virus infection by stimulating local and systemic immune responses. Cellular components of lactobacilli may be pivotal in protecting against viral infection by enhancing gut and respiratory immune responses. PMID- 22098225 TI - Mineralocorticoid receptor antagonists for heart failure. PMID- 22098224 TI - Bioavailability of phytochemical constituents from a novel soy fortified lycopene rich tomato juice developed for targeted cancer prevention trials. AB - Studies suggest that tomato and soy foods may contribute to a lower risk of certain cancers. We developed a novel soy germ tomato juice to be used in controlled cancer prevention trials. This study describes an initial test of compliance, phytochemical bioavailability, and effects on biomarkers of blood lipids. Healthy men and women (n = 18) consumed a soy germ-fortified juice daily (300 mL supplying 66 mg isoflavones and 22 mg lycopene) for 8 wk. A single-dose bioavailability study was completed on day 1 and isoflavones in plasma and urine, and lycopene in the plasma, were measured. All subjects completed the trial, with 97.7% +/- 3.5% (mean +/- SD) of the scheduled juice consumed. No adverse effects were documented. The postprandial study indicated that 3.1% +/- 2.3% of lycopene was absorbed and that 49.3% +/- 12.1% isoflavones ingested were recovered in 24-h urines. Lycopene plasma concentration changed from 0.60 +/- 0.22 to 1.24 +/- 0.30 MUmol/L during 8 wk of consumption. Juice consumption significantly improved resistance of LDL+VLDL-C to Cu(2+)-mediated oxidation (P = 0.039), HDL-C (47.3 +/ 15.8 to 51.7 +/- 14.8 mg/dL, P < 0.001), and the ratio of total-C/HDL-C (4.25 +/ 1.59 to 3.63 +/- 1.16, P < 0.001) at 8 wk. A well-characterized soy-fortified tomato juice can be produced in large scale for multiinstitutional long-term cancer prevention trials and showed excellent compliance with no toxicity, while demonstrating absorption of biologically active phytochemicals. PMID- 22098226 TI - Could the underestimation of bipolarity obstruct the search for novel antidepressant drugs? AB - INTRODUCTION: Despite the clinical and social relevance of depression, and the availability of numerous antidepressants and non-pharmacological interventions, response rates remain unsatisfactory and novel therapeutic targets are being explored. AREAS COVERED: This review starts with a brief overview of the evolution of the current antidepressant drug scenario and ends with a focus on the potential influence of the underestimation of bipolarity on the exploration of novel antidepressant drugs. EXPERT OPINION: The field of antidepressant drug development has suffered from a relative decline recently and, with the exception of agomelatine, innovative non-monoaminergic antidepressants have yet to be developed. The need for more effective compounds is evident. Clinicians and researchers should pay greater attention to the impact of bipolarity in depression. The ultimate goal of this review is not to discourage the use of antidepressants but rather to encourage judicious prescriptions, and also to solicit a better collaboration between clinicians and preclinical researchers so that more reliable diagnostic criteria can be adopted. PMID- 22098227 TI - Treatment strategies for chronic stable angina. AB - INTRODUCTION: Stable angina pectoris - generally the expression of an imbalance between myocardial oxygen demand and supply - is often the first manifestation of ischemic heart disease. The effective management of this highly prevalent condition is largely dependent on the identification of the prevailing pathogenic mechanism, the implementation of lifestyle changes and the appropriate use of pharmacological agents and revascularization techniques. There is abundant literature on management of chronic stable angina, but publications are generally devoted to focused areas. There is a need for a comprehensive review that addresses both the different types of angina and their pathogenic mechanisms, as well as rational approaches to patient management. AREAS COVERED: This paper reviews the pathogenesis and pathophysiological mechanisms of myocardial ischemia, along with its consequences and current treatment options. Relevant papers in the English literature were identified via PubMed, using the following keywords relating to chronic stable angina: ischemic heart disease, coronary artery disease and antianginal therapy. EXPERT OPINION: The treatment of chronic stable angina has improved in recent years as a result of a better understanding of its pathogenic mechanisms, the implementation of lifestyle changes and aggressive management of risk factors, as well as pharmacological advances and better revascularization techniques. Understanding the pathogenesis of the disease is important to identify effective treatment strategies. A careful clinical history, the implementation of appropriate diagnostic tests and a rational use of antianginal drugs and revascularization protocols often ensure the successful control of the patient's symptoms. PMID- 22098228 TI - Treating chronic lymphocytic leukemia with thalidomide and lenalidomide. AB - INTRODUCTION: Chronic lymphocytic leukemia (CLL) is biologically, as well as clinically, highly heterogeneous. In CLL patients, immunosuppression is a consequence of the disease, which plays a key role in effecting the quality of life and overall survival. Treatment modalities should ideally not only reduce tumor burden, but also augment immune function in CLL patients. AREAS COVERED: The current review summarizes biological and clinical data on thalidomide and lenalidomide in CLL. EXPERT OPINION: Immunomodulatory drugs such as thalidomide and lenalidomide show both antitumor activity and immunostimulation. Three main mechanisms of action seem to play a role in cancer, including i) anti-angiogenic, ii) immunomodulatory and iii) tumoricidal effects. The exact contributions of these effects seem to be unique for different diseases. The two representatives of this family of drugs studied in CLL include thalidomide and its analog lenalidomide. These drugs proved to be effective as single agents and in the combination setting in CLL. Toxicities have been identified but largely controlled by a low starting dose, with gradual dose escalation. PMID- 22098229 TI - Progress and contrasts of the development of tivozanib for therapy of kidney cancer. AB - INTRODUCTION: Targets for drug development for the treatment of kidney cancer (renal cell carcinoma; RCC) include vascular endothelial growth factor (VEGF) and its receptors and mammalian target of rapamycin. Currently available oral multitargeted VEGF tyrosine kinase inhibitors (TKIs) that have been approved by the US Food and Drug Administration for advanced RCC, include sunitinib, sorafenib and pazopanib. Off-target TKI inhibition can potentially preclude full dose combination with other targeted and chemotherapeutic agents. There is a need to develop more potent and selective targeted agents for RCC therapy, which are more effective and have minimal off-target effects. AREAS COVERED: This drug evaluation review addresses the ongoing development for the treatment of RCC with tivozanib: a potent, selective and long-half-life VEGF TKI. The testing for clinical efficacy alone or in combination with other therapies for RCC and for other tumor types, and the clinical and market relevance of introducing another RCC therapy are discussed. EXPERT OPINION: Tivozanib is distinguished by its high potency, selectivity, long-half-life and its potential to be effectively combined with other agents in RCC. This may offer more effective, yet well-tolerated treatment options. The relative clinical and market relevance remain to be seen, both for RCC therapy and other tumor types. PMID- 22098230 TI - Desvenlafaxine in the treatment of major depressive disorder. AB - Desvenlafaxine (DESV) is a newer antidepressant, which inhibits serotonin norepinephrine reuptake neurotransmission, similarly to venlafaxine, milnacipran and duloxetine. It was approved in February 2008 by the FDA for the treatment of major depressive disorder (MDD), based on well-controlled and adequately powered, large clinical trials demonstrating efficacy and safety for patients with MDD. Currently available data show that DESV has proven efficacy, acceptable safety and tolerability profiles, convenient once-daily dosing and minimal impact on the cytochrome P450 enzyme system in patients with MDD. This mini-review summarizes the clinical data and practical use of DESV under this approved indication. PMID- 22098231 TI - Innovative antidepressants: jumping out of the monoamine-based theory? PMID- 22098233 TI - Pleiotropic functions of brain proteinases: methodological considerations and search for caspase substrates. AB - Analysis of the literature and our own data suggest that the so-called "apoptotic" proteinases play important roles in brain function. However, mechanisms of their involvement in normal neuronal plasticity remain obscure. One of the main reasons for this is broad substrate specificity of proteinases; the number of potential substrates of each can reach several thousands. Obviously, a real approach to study functions of "apoptotic" proteinases, caspase-3 in particular, is to identify their intracellular substrates. It is the nature of a substrate that defines the direction of signal transduction or metabolic changes; therefore, identification of molecular partners of particular proteases should be the key study, not just measuring its activity or respective protein or mRNA expression. This approach will allow studying regulatory mechanisms not only for proteinases, but also for other pleiotropic enzymes usually possessing broad substrate specificity. PMID- 22098234 TI - Constitutive androstane receptor (CAR) is a xenosensor and target for therapy. AB - Constitutive androstane receptor (CAR, NR1I3), which is under consideration in this review, is a member of the superfamily of nuclear receptors. However, certain features distinguish CAR from the variety of nuclear receptors. First, this receptor has structural features that allow it to display constitutive activity in the absence of a ligand and to interact in a species-specific manner with a huge number of ligands diverse in chemical structure and origin. Second, recently many researchers are focused on CAR because the significance is increasingly shown of its influence on a variety of physiological functions, such as gluconeogenesis, metabolism of xenobiotics, fatty acids, bilirubin, and bile acids, hormonal regulation, etc. In addition to the fundamental scientific interest, the study of CAR is of practical importance because changes in CAR activity can lead to disorders in physiological processes, which finally can result in changes in pathological states. However, despite intensive studies, many mechanisms are still unclear, which makes it difficult to understand the role of CAR in the overall picture of molecular regulation of physiological processes. This review analyzes the features and diversity of the functions of CAR. PMID- 22098235 TI - Characteristics of sigma-dependent pausing by RNA polymerases from Escherichia coli and Thermus aquaticus. AB - The sigma(70) subunit of RNA polymerase (RNAP) is the major transcription initiation factor in Escherichia coli. During transcription initiation, conserved region 2 of the sigma(70) subunit interacts with the -10 promoter element and plays a key role in DNA melting around the starting point of transcription. During transcription elongation, the sigma(70) subunit can induce pauses in RNA synthesis owing to interactions of region 2 with DNA regions similar to the -10 promoter element. We demonstrated that the major sigma subunit from Thermus aquaticus (sigma(A)) is also able to induce transcription pausing by T. aquaticus RNAP. However, hybrid RNAP containing the sigma(A) subunit and E. coli core RNAP is unable to form pauses during elongation, while being able to recognize promoters and initiate transcription. Inability of the sigma(A) subunit to induce pausing by E. coli RNAP is explained by the substitutions of non-conserved amino acids in region 2, in the subregions interacting with the RNAP core enzyme. Thus, changes in the structure of region 2 of the sigma(70) subunit have stronger effects on transcription pausing than on promoter recognition, likely by weakening the interactions of the sigma subunit with the core RNAP during transcription elongation. PMID- 22098236 TI - Coherent phenomena of charge separation in reaction centers of LL131H and LL131H/LM160H/FM197H mutants of Rhodobacter sphaeroides. AB - Primary stage of charge separation and transfer of charges was studied in reaction centers (RCs) of point mutants LL131H and LL131H/LM160H/FM197H of the purple bacterium Rhodobacter sphaeroides by differential absorption spectroscopy with temporal resolution of 18 fsec at 90 K. Difference absorption spectra measured at 0-4 psec delays after excitation of dimer P at 870 nm with 30 fsec step were obtained in the spectral range of 935-1060 nm. It was found that a decay of P* due to charge separation is considerably slower in the mutant RCs in comparison with native RCs of Rba. sphaeroides. Coherent oscillations were found in the kinetics of stimulated emission of the P* state at 940 nm. Fourier analysis of the oscillations revealed a set of characteristic bands in the frequency range of 20-500 cm(-1). The most intense band has the frequency of ~130 cm(-1) in RCs of mutant LL131H and in native RCs and the frequency of ~100 cm(-1) in RCs of the triple mutant. It was found that an absorption band of bacteriochlorophyll anion B(A)(-) which is registered in the difference absorption spectra of native RCs at 1020 nm is absent in the analogous spectra of the mutants. The results are analyzed in terms of the participation of the B(A) molecule in the primary electron transfer in the presence of a nuclear wave packet moving along the inharmonic surface of P* potential energy. PMID- 22098237 TI - Programmed cell death in plants: protective effect of mitochondrial-targeted quinones. AB - Ubiquinone or plastoquinone covalently linked to synthetic decyltriphenylphosphonium (DTPP(+)) or rhodamine cations prevent programmed cell death (PCD) in pea leaf epidermis induced by chitosan or CN(-). PCD was monitored by recording the destruction of cell nuclei. CN(-) induced the destruction of nuclei in both epidermal cells (EC) and guard cells (GC), whereas chitosan destroyed nuclei in EC not in GC. The half-maximum concentrations for the protective effects of the quinone derivatives were within the pico- and nanomolar range. The protective effect of the quinones was removed by a protonophoric uncoupler and reduced by tetraphenylphosphonium cations. CN(-)-Induced PCD was accelerated by the tested quinone derivatives at concentrations above 10(-8)-10( 7) M. Unlike plastoquinone linked to the rhodamine cation (SkQR1), DTPP(+) derivatives of quinones suppressed menadione-induced H(2)O(2) generation in the cells. The CN(-)-induced destruction of GC nuclei was prevented by DTPP(+) derivatives in the dark not in the light. SkQR1 inhibited this process both in the dark and in the light, and its effect in the light was similar to that of rhodamine 6G. The data on the protective effect of cationic quinone derivatives indicate that mitochondria are involved in PCD in plants. PMID- 22098238 TI - New Actinoporins from sea anemone Heteractis crispa: cloning and functional expression. AB - A new actinoporin Hct-S4 (molecular mass 19,414 +/- 10 Da) belonging to the sphingomyelin-inhibited alpha-pore forming toxin (alpha-PFT) family was isolated from the tropical sea anemone Heteractis crispa (also called Radianthus macrodactylus) and purified by methods of protein chemistry. The N-terminal nucleotide sequence (encoding 20 amino acid residues) of actinoporin Hct-S4 was determined. Genes encoding 18 new isoforms of H. crispa actinoporins were cloned and sequenced. These genes form a multigene Hct-S family characterized by presence of N-terminal serine in the mature proteins. Highly conserved residues comprising the aromatic phosphorylcholine-binding site and significant structure function changes in the N-terminal segment (10-27 amino acid residues) of actinoporins were established. Two expressed recombinant actinoporins (rHct-S5 and rHct-S6) were one order less hemolytically active than native actinoporins. PMID- 22098239 TI - Identification of proteins responding to adrenergic receptor subtype-specific hypertrophy in cardiomyocytes by proteomic approaches. AB - The individual signaling pathways underlying cardiac hypertrophy, which is induced by either alpha or beta adrenergic receptor (AR), are different. Activation of different AR subtypes couples to different G proteins and induction of specific signaling pathways, which ultimately results in subtype-specific regulation of cardiac function. We present the first proteomics study identifying proteins that are related to AR subtype-specific hypertrophy in cardiomyocytes by comparing the two-dimensional electrophoresis patterns between neonatal rat cardiomyocytes treated by phenylepinephrin (PE) and by isoproterenol (ISO). An improved 2-DE strategy was used in these comparative experiments. Twenty-five differentially expressed proteins in cardiomyocytes treated by PE or treated by ISO were successfully analyzed and identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry, especially those that might be responsible to intracellular oxidative stress such as dismutase, peroxiredoxin, and thioredoxin-like protein p46. In addition, induced reactive oxygen species were also found to be AR subtype-specifically relevant to endoplasmic reticulum proteinase ERK1/2 phosphorylation during the development of hypertrophy induced by different AR subtypes. The results will help to better understand the underlying mechanisms of different adrenergic receptor subtype induced hypertrophy. PMID- 22098240 TI - Site-directed mutagenesis of cysteine residues of Luciola mingrelica firefly luciferase. AB - Single mutants (C62S, C62V, C86S, C146S, C164S), double mutants (C62/146S, C62/164S, C86/146S, C146/164S), and triple mutant C62/146/164S of the Luciola mingrelica firefly luciferase carrying C-terminal His(6)-tag were obtained on the basis of plasmid pETL7 by site-directed mutagenesis. Bioluminescence and fluorescence spectra were not altered by the introduced mutations. In the case of mutants C86S, C86/146S, C62/164S, and the triple mutant C62/146/164S, the K(m)(ATP) and K(m)(LH)(2) values were increased by a factor of ~1.5-1.9. Their expression level, specific activity, and thermal stability were significantly decreased. The other mutations had almost no effect on the K(m)(ATP) and K(m)(LH)(2) values, specific activity, and thermal stability of the enzyme. Thermal stability of the C146S mutant was increased by a factor of ~2 and 1.3 at 37 and 42 degrees C, respectively. The possible mechanism of the influence of these mutations on properties and structure of the enzyme is discussed. PMID- 22098241 TI - Self-assembly of soluble unlinked and cross-linked fibrin oligomers. AB - Self-assembly of soluble unlinked and cross-linked fibrin oligomers formed from desA-fibrin monomer under the influence of factor XIIIa was studied in the presence of non-denaturing urea concentrations. By methods of elastic and dynamic light scattering combined with analytical ultracentrifugation, desA-fibrin oligomers formed in both the presence and absence of the factor XIIIa were shown to be ensembles consisting of soluble rod-like double-stranded protofibrils with diverse weight and size. Unlinked and cross-linked soluble double-stranded protofibrils can reach the length of 350-450 nm. The structure of soluble covalently-linked protofibrils is stabilized by isopeptide gamma-dimers. Electrophoretic data indicate a complete absence of isopeptide bonds between alpha-chains of desA-fibrin molecules. The molecular mechanism of formation of soluble rod-like fibrin structures and specific features of its covalent stabilization under the influence of factor XIIIa are discussed. PMID- 22098242 TI - Methylglyoxal induces mitochondria-dependent apoptosis in sarcoma. AB - In the preceding paper (A. Ghosh et al. (2011) Biochemistry (Moscow), 76, 1051 1060), using several comparable tissue materials, it has been convincingly demonstrated that methylglyoxal, a normal metabolite, inhibits mitochondrial complex I of specifically malignant cells. This suggests a distinct alteration of complex I, a highly important enzyme for energy (ATP) production, in malignancy. The present paper shows that as a consequence of this inhibition mitochondrial membrane potential is drastically reduced in sarcoma tissue but not in normal skeletal muscle. This was estimated spectrofluorimetrically using the dye rhodamine 123. As a consequence, cytochrome c was released from the sarcoma mitochondria as evidenced by Western blot analysis. Moreover, on treatment with methylglyoxal membrane potential collapse of sarcoma 180 cells was also indicated by fluorescence-activated cell sorter analysis. Atomic force microscopic study demonstrated gross structural alteration specifically of tumor mitochondria on methylglyoxal treatment. All these studies suggest that methylglyoxal might initiate an apoptotic event in malignant cells. PMID- 22098243 TI - Effect of cholinergic drugs on the activity of basic carboxypeptidases in rat nervous tissue. AB - Effects of a single administration of cholinergic drugs (arecoline, atropine, nicotine, mecamylamine) on the activity of carboxypeptidase H and of phenylmethylsulfonyl fluoride-inhibited carboxypeptidase, which are involved in metabolism of neuropeptides, were studied in brain parts and the adrenal glands of rats. The enzyme activities were determined fluorimetrically using specific inhibitors and substrates. In the majority of cases the enzyme activities decreased, and this decrease was retained for at least 72 h. Changes in the activities of the studied enzymes depended on the type of cholinergic action, the nervous system part, and the time after the injection. The changes in activities of the studied carboxypeptidases are supposed to be a possible mechanism responsible for changes in the levels of neuropeptides under the influence of high doses of the drugs. PMID- 22098244 TI - Contents of mRNAs encoding endosome/lysosome components in normal human aorta and in stage II of atherogenesis: a hidden regulation. AB - Contents of mRNAs encoding endosome/lysosome components EEA1, Rab5a, Lamp1, Lamp2, p62 (SQSTM1), and CD63 were measured by quantitative PCR and compared in intact fragments of human aorta and in aorta fragments with atherosclerotic lesions of stage II (fatty streaks) of the same donors. During atherogenesis an increase was detected only in the level of p62 mRNA but not in other mRNAs. Nevertheless, correlation analysis revealed a profound rearrangement of inter gene correlations: only 30% of correlations found in the fatty streaks coincided with the correlations in normal fragments. Thus, new constellations were formed in fatty streaks concurrently with disappearance of correlations between mRNAs under study and mRNAs encoding factors of lipid accumulation, reverse cholesterol transfer, and some lipid sensors/transcription regulators of lipid metabolism. PMID- 22098245 TI - Carbohydrate specificity of chicken and human tandem-repeat-type galectins-8 in composition of cells. AB - The network of adhesion/growth-regulatory galectins in chicken (chicken galectin, CG) has only one tandem-repeat-type protein, CG8. Using a cell-based assay and probing galectin reactivity with a panel of fluorescent neoglycoconjugates (glycoprobes), its glycan-binding profile was determined. For internal validation, human galectin-8 (HG8) was tested. In comparison to HG8, CG8 showed a rather similar specificity: both galectins displayed high affinity to blood group ABH antigens as well as to 3'-sialylated and 3'-sulfated lactosamine chains. The most remarkable difference was found to be an ability of HG8 (but not CG8) to bind the disaccharide Galbeta1-3GlcNAc (Le(c)) as well as branched and linear oligolactosamines. The glycan-binding profile was shown to be influenced by glycocalix of the cell, where the galectin is anchored. Particularly, glycosidase treatment of galectin-loaded cells led to the change of the profile. Thus, we suppose the involvement of cis-glycans in the interaction of cell-anchored galectins with external glycoconjugates. PMID- 22098246 TI - Single nucleotide polymorphisms associated with metastatic tumour antigen 1 overexpression in patients with hepatocellular carcinoma. AB - BACKGROUNDS/AIMS: Metastatic tumour antigen 1 (MTA1) promotes angiogenesis by stabilizing hypoxia-inducible factor-1alpha (HIF-1alpha), which is closely associated with frequent postoperative recurrence and poor survival in patients with HCC. In this study, we determined single nucleotide polymorphisms (SNPs) in angiogenesis-related genes that are associated with MTA1 overexpression in HCC tissues. METHODS: A total of 376 patients with HCC who had received curative surgical resection or liver transplantation were enrolled (312/21/43; HBV/HCV/NBNC). MTA1 expression was determined via immunohistochemistry. Thirty three common SNPs sites (frequency >=5%) in the angiogenic protein gene that are closely connected to one another were selected, including MTA1, VEGF, HIF-1alpha, FGF-2, and IGF-II. RESULTS: Expression of MTA1 was detected in 120 HCC tissues (31%). An A allele at position IVS4-81G/A of the MTA1 gene (P = 0.016) and the TT genotype at position +12916C of the VEGF gene (P = 0.023) were significantly associated with MTA1 overexpression. However, the TT genotype at position -13021C (P = 0.011) and the haplotypes CT-CT (-11228C; -13021C) of the IGF-II gene (P(cor) = 0.033) were more common in patients with MTA1-negative HCC. Using multivariate analysis, the A allele at IVS4-81G/A in MTA1 gene (P = 0.015) and a T allele (TT+CT genotype) at -13021C in IGF-II (P = 0.002) were independent risk factors in HCC recurrence after curative surgical resection. CONCLUSIONS: The genetic polymorphisms IVS4-81G/A in MTA1 and +12916C in VEGF genes were correlated with MTA1 overexpression. The SNPs in MTA1 and IGF-II genes may be important risk factors for the recurrence of HCC. PMID- 22098247 TI - Fabrication of flocculation-resistant pH/ionic strength/temperature multiresponsive hollow microspheres and their controlled release. AB - pH/ionic strength/temperature multiresponsive hollow microspheres were successfully prepared by the Ce(IV) initiated grafting polymerization of N isopropylacrylamide (NIPAm) onto the multilayered polyelectrolyte shells encapsulating the polystyrene sulfonate (PSS) microsphere templates fabricated by the layer-by-layer assembly of chitosan (CS) and alginate (SAL), after etching the templates by dialysis. The hollow structure of the obtained multiresponsive hollow microspheres was characterized by transmission electron microscopy (TEM), which indicated that the inner diameter of the hollow microspheres was about 200 nm. The environmental responsive properties of the multiresponsive hollow microspheres were characterized with dynamic light scattering (DLS) in an aqueous system. The introduction of poly(N-isopropylacrylamide) (PNIPAm) brushes onto the pH/ionic strength dual-responsive hollow microspheres achieved temperature responsive characteristics. It also could prevent flocculation among the obtained multiresponsive hollow microspheres in a solution with higher salt concentration. Their controlled release of drug molecules (a model hydrophobic drug, dipyridamole (DIP)) was also investigated. PMID- 22098249 TI - Income-related inequalities in denture-wearing by Europeans aged 50 and above. AB - BACKGROUND: Despite its importance for the planning of future treatment needs and an optimised allocation of health care resources, only little is known about socio-economic inequalities in denture-wearing by late middle-aged and elderly generations. OBJECTIVES: To describe income-related inequalities in denture wearing by elderly populations residing in different European countries. MATERIAL AND METHODS: Data from the Survey of Health, Ageing and Retirement in Europe (SHARE Wave 2) were used to assess income-related inequalities in denture-wearing by means of Concentration Indices (CI) for populations aged 50+ from 14 different European countries. RESULTS: We could identify a significant disproportionate concentration of denture-wearing amongst the poor elderly populations in Denmark (CI = -0.3534, corresponding to the highest level of inequality), Sweden (CI = 0.3479), Switzerland (CI = -0.2013), Greece (CI = -0.1953), the Netherlands (CI = -0.1413), France (CI = -0.1339), Austria (CI = -0.0974), Czech Republic (CI = 0.0959), Belgium (CI = -0.0947), Germany (CI = -0.0762), Ireland (CI = -0.0575) and Spain (CI = -0.0482, corresponding to the lowest level of pro-poor inequality). Poland became evident as the only country in which individuals from the upper end of the income scale wear more dentures than their peers from the lower end of the income scale (CI = 0.0379). No significant income-related inequalities were observable in Italy. CONCLUSIONS: There is considerable income related inequality in denture-wearing by several elderly populations in Europe. Future resource planning for prosthetic care should, thus, specifically distinguish between the treatment needs of different socio-economic groups within elderly populations. PMID- 22098248 TI - Glutamatergic input is selectively increased in dorsal raphe subfield 5-HT neurons: role of morphology, topography and selective innervation. AB - Characterization of glutamatergic input to dorsal raphe (DR) serotonin (5-HT) neurons is crucial for understanding how the glutamate and 5-HT systems interact in psychiatric disorders. Markers of glutamatergic terminals, vGlut1, 2 and 3, reflect inputs from specific forebrain and midbrain regions. Punctate staining of vGlut2 was homogeneous throughout the mouse DR whereas vGlut1 and vGlut3 puncta were less dense in the lateral wing (lwDR) compared with the ventromedial (vmDR) subregion. The distribution of glutamate terminals was consistent with the lower miniature excitatory postsynaptic current frequency found in the lwDR; however, it was not predictive of glutamatergic synaptic input with local activity intact, as spontaneous excitatory postsynaptic current (sEPSC) frequency was higher in the lwDR. We examined the morphology of recorded cells to determine if variations in dendrite structure contributed to differences in synaptic input. Although lwDR neurons had longer, more complex dendrites than vmDR neurons, glutamatergic input was not correlated with dendrite length in the lwDR, suggesting that dendrite length did not contribute to subregional differences in sEPSC frequency. Overall, glutamatergic input in the DR was the result of selective innervation of subpopulations of 5-HT neurons and was rooted in the topography of DR neurons and the activity of glutamate neurons located within the midbrain slice. Increased glutamatergic input to lwDR cells potentially synergizes with previously reported increased intrinsic excitability of lwDR cells to increase 5-HT output in lwDR target regions. Because the vmDR and lwDR are involved in unique circuits, subregional differences in glutamate modulation may result in diverse effects on 5-HT output in stress-related psychopathology. PMID- 22098250 TI - Effect of copper hydroxide sprays for citrus canker control on wild-type Escherichia coli. AB - AIMS: To show that application of copper hydroxide citrus sprays mixed with field source water (possibly contaminated) will not support Escherichia coli on plant surfaces. Environmental stresses of transient phyllosphere bacteria and presence of copper will eradicate these bacteria before harvest. METHODS AND RESULTS: Studies were performed in vitro with bacteria grown in broth and then subjected to field spray copper hydroxide concentrations in the broth and on citrus leaves. Escherichia coli exposed to copper hydroxide in vitro were eradicated from the broth within 6-8 h depending on the broth pH. Even with near neutral pH (7.2), cells began to die immediately after exposure to copper. No E. coli survived on leaf surfaces sprayed with copper. CONCLUSIONS: Copper field sprays mixed with water that may contain E. coli can help eliminate E. coli from plant surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: HACCP mandates are becoming more restrictive because of the increased illness resulting from food pathogens on fresh produce. Use of potable water in fields, a proposed mandate, is not feasible for large grove owners. These data show that copper sprays aimed at reducing citrus canker also affect E. coli and may help to ease water quality mandates. PMID- 22098251 TI - Preconditioning donor liver with Nodosin perfusion lessens rat ischemia reperfusion injury via heme oxygenase-1 upregulation. AB - BACKGROUND AND AIM: Ischemia reperfusion injury (IRI) remains a major cause of graft injury, dysfunction and even failure post-transplantation. Heme oxygenase 1 (HO-1) has been found to be an attractive target for anti-inflammatory therapies and a potential candidate responsible for cell injury. The objective of this study was to investigate whether preconditioning the donor liver with Nodosin perfusion upregulates HO-1 and then lessens IRI in rat models. METHODS: Wistar rats were divided into four groups: experimental group, control group, positive control group and negative control group in which the donor liver was preconditioned with Nodosin, lactated ringer's solution, cobalt protoporphyrin and zinc protoporphyrin perfusion, respectively. We measured HO-1 expression and enzyme activity in rat livers of each group ex vivo at 0, 1 and 2 h after perfusion. At 1 h after perfusion, donor livers of Wistar rats were transplanted into Sprague-Dawley rats orthotopically. Serum transaminase levels, degree of cell apoptosis and Suzuki's score were used to assess ischemia/reperfusion injury in recipients at 24 h after transplantation. RESULTS: Ex vivo, donor liver preconditioning with Nodosin perfusion induced HO-1 expression and enzyme activity significantly, compared with the control group (P < 0.05). In vivo, serum transaminase levels, cell apoptosis degree and Suzuki's score of representative recipients in the Nodosin group were lower than that in the control group (P < 0.05). Preconditioning with Nodosin perfusion induced HO-1 protein mainly in Kupffer cells. CONCLUSIONS: This study suggests that preconditioning with Nodosin perfusion provides a potential protective effect through inducing HO-1 expression to attenuate ischemia/reperfusion injury in liver transplantation. PMID- 22098252 TI - Predictive factors of PACU stay after herniorraphy in infant: a classification and regression tree analysis. AB - INTRODUCTION: Herniorraphy is a common surgical intervention in infants, particularly in those born prematurely. Prematurity and perioperative sedation have been shown to be risk factors for postoperative apnea. However, their influence upon PACU stay duration has not been evaluated. The goal of this study was to investigate predictive factors for PACU stay in infants undergoing herniorraphy. MATERIAL AND METHODS: This study is a retrospective analysis of perioperative data in infants <6 months of age undergoing herniorraphy during the period November 2007-November 2009. Collected data included age, gestational age at birth, post-conceptional age, weight, weight at birth, type of anesthesia (spinal vs general), perioperative administration of opioids and paracetamol, duration of surgery, duration of PACU stay, and apnea in PACU. Data analysis used classification and regression trees (CART) with a 10-fold cross-validation. RESULTS: Two hundred and ninety-six patients were included in the analysis. Five parameters were found to predict the duration of PACU stay: a post-conceptional age below 45 weeks, prematurity, general anesthesia, postoperative opioid administration, and the use of intraoperative regional analgesia. CRT method allows constructing a decision tree with eight terminal nodes. The percentage of explained variability of the model and the cross-validation were 79.7% and 76.6%, respectively. DISCUSSION: Our study allows construction of an accurate predictive tree for PACU stay during herniorraphy in infants <6 months. Parameters found to influence the duration of PACU stay were related to anesthesia techniques and perinatal outcomes. PMID- 22098253 TI - Bacteriology of hidradenitis suppurativa exacerbations and deep tissue cultures obtained during carbon dioxide laser treatment. AB - BACKGROUND: Previous studies have shown different bacteria in hidradenitis suppurativa (HS) lesions, but the literature regarding bacteria in acute exacerbation of HS is sparse. OBJECTIVES: To determine the type of bacteria isolated from HS lesions during exacerbations of the disease. METHODS: Patients with HS with acute nodules or abscesses were examined and treated by carbon dioxide laser vaporization. Bacterial samples for aerobic and anaerobic cultures were taken from the skin surface (before surgery) and then from the deeper layers (during surgery) of the lesions. At each level two samples were taken, one with a punch biopsy and one by pressing a soft agar gel against the skin. The bacterial findings were typed and quantified. RESULTS: A total of 10 patients (eight women and two men), with a mean age of 37.2 years and a mean HS duration of 14.5 years, were included. All of them had an ongoing exacerbation (mean duration 5.6 days) of their HS, with one inflamed lesion that was treated by carbon dioxide laser vaporization. Coagulase-negative staphylococci (CNS) were found in the deep layers in all 10 patients. Nine of the patients carried Corynebacterium spp. and two alpha-haemolytic streptococci at various levels. Among the anaerobic microorganisms, Gram-positive cocci were the most common bacteria. CONCLUSIONS: As found in a previous study, CNS were the most common bacteria, but contrary to what we expected, Staphylococcus aureus was not found in any cultures from acute inflammatory nodules of HS exacerbations. PMID- 22098254 TI - Surface characterization, collagen adsorption and cell behaviour on poly(L lactide-co-glycolide). AB - Poly(L-lactide-co-glycolide) (PLG) was modified through the adsorption of collagen to improve the behaviour of fibroblasts and osteoblasts. As reference materials cell-resistant polystyrene (PS) and cell-conductive tissue-culture polystyrene (TCPS) were also evaluated. The physicochemical surface properties of the materials were studied by X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and water contact angle measurements. The morphology of cells was examined using optical microscopy, while their growth was evaluated by both crystal violet and MTT tests. Nitric oxide level and protein concentration were tested in cell supernatants. The results showed that the adsorbed amount and the organization of the adsorbed collagen were influenced by surface hydrophobicity. Cell culture experiments on native substrates revealed that cell attachment, spreading and growth enhanced, depending on the substrate, in the following order: PS60) showed equal improvement of the OHRQoL. In the IFPD group, patients older than 60 years showed better improvement (p < 0.05). There were no significant differences dependent on gender and antagonistic teeth (p > 0.05). CONCLUSION: The FPD and the IFPD treatment showed significant improvement of OHRQoL. The FPD treatment improved OHRQoL equally in both age groups, while the IFPD treatment improved OHRQoL better in older patients. PMID- 22098295 TI - Developmental regulation of G protein-gated inwardly-rectifying K+ (GIRK/Kir3) channel subunits in the brain. AB - G protein-gated inwardly-rectifying K(+) (GIRK/family 3 of inwardly-rectifying K(+) ) channels are coupled to neurotransmitter action and can play important roles in modulating neuronal excitability. We investigated the temporal and spatial expression of GIRK1, GIRK2 and GIRK3 subunits in the developing and adult brain of mice and rats using biochemical, immunohistochemical and immunoelectron microscopic techniques. At all ages analysed, the overall distribution patterns of GIRK1-3 were very similar, with high expression levels in the neocortex, cerebellum, hippocampus and thalamus. Focusing on the hippocampus, histoblotting and immunohistochemistry showed that GIRK1-3 protein levels increased with age, and this was accompanied by a shift in the subcellular localization of the subunits. Early in development (postnatal day 5), GIRK subunits were predominantly localized to the endoplasmic reticulum in the pyramidal cells, but by postnatal day 60 they were mostly found along the plasma membrane. During development, GIRK1 and GIRK2 were found primarily at postsynaptic sites, whereas GIRK3 was predominantly detected at presynaptic sites. In addition, GIRK1 and GIRK2 expression on the spine plasma membrane showed identical proximal-to-distal gradients that differed from GIRK3 distribution. Furthermore, although GIRK1 was never found within the postsynaptic density (PSD), the level of GIRK2 in the PSD progressively increased and GIRK3 did not change in the PSD during development. Together, these findings shed new light on the developmental regulation and subcellular diversity of neuronal GIRK channels, and support the contention that distinct subpopulations of GIRK channels exert separable influences on neuronal excitability. The ability to selectively target specific subpopulations of GIRK channels may prove effective in the treatment of disorders of excitability. PMID- 22098297 TI - Energy decomposition analysis in solution based on the fragment molecular orbital method. AB - We develop the pair interaction energy decomposition analysis (PIEDA) in solution by combining the fragment molecular orbital (FMO) method with the polarizable continuum model (PCM). The solvent screening of the electrostatic interaction and the desolvation penalty in complex formation are described by this approach from ab initio calculations of fragments and their pairs. The applications to the complex of solvated sodium and chlorine ions, as well as to lysine and aspartic acid, show how the analysis helps reveal the physical picture. The PIEDA/PCM method is also applied to a small protein chignolin (PDB: 1UAO), and the solvent screening of the pair interactions is discussed. PMID- 22098296 TI - Role of vascular endothelial growth factor in angiodysplasia: an interventional study with thalidomide. AB - BACKGROUND AND AIM: The pathogenesis of angiodysplasia is still not fully understood and effective therapy is not available. Thalidomide was reported to be effective in the treatment of angiodysplasia, but the mechanisms underlying its activity are, as yet, unknown. We aimed to investigate the expression of vascular endothelial growth factor (VEGF) in angiodysplasia tissues, and the role of hypoxia-inducible factor-1alpha (HIF-1alpha) and basic fibroblast growth factor (bFGF) on VEGF expression in human umbilical vein endothelial cells (HUVEC). Additionally, we aimed to study the role of thalidomide in these parameters. METHODS: Immunohistochemistry was performed to visualize VEGF in angiodysplasia lesions. HUVEC were incubated under hypoxic conditions or in the presence of bFGF. Effects of exposure to thalidomide were studied. Cell growth was assessed in methylthiazolyte-trazolium assays. Enzyme-linked immunosorbent assays and real time polymerase chain reaction were performed to assess the expression of VEGF at protein and mRNA levels. Western blot was performed to detect the expression of HIF-1alpha under hypoxic conditions. RESULTS: VEGF was strongly expressed in 75% of patients with angiodysplasia lesions, as compared to expression in patients without angiodysplasia lesions. VEGF was also induced in HUVEC under hypoxic conditions (P < 0.05). bFGF was found to stimulate the proliferation of HUVEC and enhance the expression of VEGF. Thalidomide suppressed bFGF-induced proliferation significantly and decreased VEGF expression, both at the protein and mRNA levels. Thalidomide also inhibited HIF-1alpha in a dose-dependent manner (P < 0.05). CONCLUSIONS: VEGF may play an important role in the pathogenesis of angiodysplasia. Thalidomide can suppress VEGF, either induced by HIF-1alpha or bFGF. PMID- 22098299 TI - Evaluating the material parameters of the human cornea in a numerical model. AB - PURPOSE: The values of the biomechanical human eyeball model parameters reported in the literature are still being disputed. The primary motivation behind this work was to predict the material parameters of the cornea through numerical simulations and to assess the applicability of the ubiquitously accepted law of applanation tonometry - the Imbert-Fick equation. METHODS: Numerical simulations of a few states of eyeball loading were run to determine the stroma material parameters. In the computations, the elasticity moduli of the material were related to the stress sign, instead of the orientation in space. RESULTS: Stroma elasticity secant modulus E was predicted to be close to 0.3 MPa. The numerically simulated applanation tonometer readings for the cornea with the calibration dimensions were found to be lower by 11 mmHg then IOP = 48 mmHg. CONCLUSIONS: This discrepancy is the result of a strictly mechanical phenomenon taking place in the tensioned and simultaneously flattened corneal shell and is not related to the tonometer measuring accuracy. The observed deviation has not been amenable to any GAT corrections, contradicting the Imbert-Fick law. This means a new approach to the calculation of corrections for GAT readings is needed. PMID- 22098298 TI - Mutagenesis of cysteine 81 prevents dimerization of the APS1 subunit of ADP glucose pyrophosphorylase and alters diurnal starch turnover in Arabidopsis thaliana leaves. AB - Many plants, including Arabidopsis thaliana, retain a substantial portion of their photosynthate in leaves in the form of starch, which is remobilized to support metabolism and growth at night. ADP-glucose pyrophosphorylase (AGPase) catalyses the first committed step in the pathway of starch synthesis, the production of ADP-glucose. The enzyme is redox-activated in the light and in response to sucrose accumulation, via reversible breakage of an intermolecular cysteine bridge between the two small (APS1) subunits. The biological function of this regulatory mechanism was investigated by complementing an aps1 null mutant (adg1) with a series of constructs containing a full-length APS1 gene encoding either the wild-type APS1 protein or mutated forms in which one of the five cysteine residues was replaced by serine. Substitution of Cys81 by serine prevented APS1 dimerization, whereas mutation of the other cysteines had no effect. Thus, Cys81 is both necessary and sufficient for dimerization of APS1. Compared to control plants, the adg1/APS1(C81S) lines had higher levels of ADP glucose and maltose, and either increased rates of starch synthesis or a starch excess phenotype, depending on the daylength. APS1 protein levels were five- to tenfold lower in adg1/APS1(C81S) lines than in control plants. These results show that redox modulation of AGPase contributes to the diurnal regulation of starch turnover, with inappropriate regulation of the enzyme having an unexpected impact on starch breakdown, and that Cys81 may play an important role in the regulation of AGPase turnover. PMID- 22098300 TI - Oxygen regulates tissue nitrite metabolism. AB - AIMS: Once dismissed as an inert byproduct of nitric oxide (NO) auto-oxidation, nitrite (NO(2)(-)) is now accepted as an endocrine reservoir of NO that elicits biological responses in major organs. While it is known that tissue nitrite is derived from NO oxidation and the diet, little is known about how nitrite is metabolized by tissue, particularly at intermediate oxygen tensions. We investigated the rates and mechanisms of tissue nitrite metabolism over a range of oxygen concentrations. RESULTS: We show that the rate of nitrite consumption differs in each organ. Further, oxygen regulates the rate and products of nitrite metabolism. In anoxia, nitrite is reduced to NO, with significant formation of iron-nitrosyl proteins and S-nitrosothiols. This hypoxic nitrite metabolism is mediated by different nitrite reductases in each tissue. In contrast, low concentrations (~3.5 MUM) of oxygen increase the rate of nitrite consumption by shifting nitrite metabolism to oxidative pathways, yielding nitrate. While cytochrome P(450) and myoglobin contribute in the liver and heart, respectively, mitochondrial cytochrome c oxidase plays a significant role in nitrite oxidation, which is inhibited by cyanide. Using cyanide to prevent artifactual nitrite decay, we measure metabolism of oral and intraperitoneally administered nitrite in mice. INNOVATION: These data provide insight into the fate of nitrite in tissue, the enzymes involved in nitrite metabolism, and the role of oxygen in regulating these processes. CONCLUSION: We demonstrate that even at low concentrations, oxygen is a potent regulator of the rate and products of tissue nitrite metabolism. PMID- 22098302 TI - Statistical perspectives: all together NOT. PMID- 22098301 TI - Rapid and slow nitric oxide responses during conducted vasodilation in the in vivo intestine and brain cortex microvasculatures. AB - Conduction of arteriolar vasodilation is initiated by activation of nitric oxide (NO) mechanisms, but dependent on conduction of hyperpolarization. Most studies have used brief (<1 second) activation of the initial vasodilation to evaluate the fast conduction processes. However, most arteriolar mechanisms involving NO production persist for minutes. In this study, fast and slower components of arteriolar conduction in the in vivo rat brain and small intestine were compared using three-minute stimulation of NO-dependent vasodilation and measurement of [NO] at the distal sites. Within 10-15 seconds, both vasculatures had a rapidly conducted vasodilation and dilation at distance had a fast but small [NO] component. A slower but larger distal vasodilation occurred after 60-90 seconds in the intestine, but not the brain, and was associated with a substantial increase in [NO]. This slowly developed dilation appeared to be caused by flow mediated responses of larger arterioles as smaller arterioles dilated to lower downstream resistance. These results indicate while the intestinal and cerebral arterioles have a fast conducted vasodilation system, the intestinal arterioles also have a slower but larger dilation of major arterioles that is NO related and dependent on the conduction of vasodilation between small arterioles. PMID- 22098304 TI - Evaluation of serum boron levels and lipid profile in pregnancies with or without gestational diabetes. AB - AIMS: Animal research has demonstrated that boron has effects on triglycerides and glucose and may act as a metabolic regulator in several enzymatic systems. Gestational diabetes mellitus (GDM) is a prevalent obstetrical complication and the lack of data on maternal status of boron in normal/diabetic pregnancies, prompted us to undertake this study. METHODS: Maternal blood samples were collected during screening and diagnosis of GDM at 24-28 weeks. Serum lipids (total cholesterol, high-density cholesterol, low density cholesterol, triglycerides, lipoprotein-a, apolipoprotein-A-I and apolipoprotein-B) and boron levels were determined. Fifteen non-GDM and 19 GDM women constituted the study population. RESULTS: The mean age was 30.1+/-5 years. The median boron levels were 15.2 MUg/L (0.0152 ppm; range, 8.4-25.4 MUg/L). When GDM and non-GDM cases were compared for age, gravidity, parity, lipid profiles and serum boron levels, no significant differences were found (P>0.05). No correlation was found between lipids and boron levels. CONCLUSION: This preliminary study contributes to the limited information about the metabolic aspects of boron. Considering the evidence that boron acts as a regulator of energy substrate utilization, the effect of dietary boron on glucose metabolism deserves further research. PMID- 22098305 TI - Vitamin D status during normal pregnancy and postpartum. A longitudinal study in 141 Danish women. AB - BACKGROUND/OBJECTIVES: To assess vitamin D status during normal pregnancy and in the postpartum lactation period. SUBJECTS/METHODS: The study comprised 141 healthy, ethnic Danish women with normal pregnancies, who were residents in Greater Copenhagen. Serum 25-hydroxy-vitamin D2+D3(25-OH-vitamin D) was measured at 18, 32 and 39 weeks' gestation and 8 weeks postpartum. RESULTS: There was a significant increase in 25-OH-vitamin D from 18 to 32 weeks' gestation (P=0.0001) followed by a significant decrease from 32 to 39 weeks (P=0.001) as well as from 39 weeks to 8 weeks postpartum (P<0.0001). At 18, 32, 39 weeks' gestation and 8 weeks postpartum, median 25-OH-vitamin D values were 77, 98, 91, and 73 nmol/L, respectively. During pregnancy and postpartum, none of the women displayed severe vitamin D deficiency (values <13 nmol/L). Between 1.4% and 4.3% of the participants displayed moderate vitamin D deficiency (values 13-24 nmol/L), 16 19% displayed vitamin D insufficiency (values 25-50 nmol/L), 77-84% had values >50 nmol/L and 0.7-2.8% had values >200 nmol/L. CONCLUSIONS: Low vitamin D status is frequent among pregnant Danish women, especially in late pregnancy and during lactation. Median dietary intake of vitamin D in women of reproductive age was 2.4 MUg/day (10-90 percentile range=1.4-5.0). The recommendations for vitamin D supplementation prior to conception, during pregnancy and lactation should be reconsidered. PMID- 22098306 TI - How does the duration of active pushing in labor affect neonatal outcomes? AB - AIM: To assess the effect of time of active pushing (TAP) on neonatal outcome. MATERIALS AND METHODS: The study population (n=36,432) was taken from a Swedish randomized control trial on intrapartum monitoring, a European Union fetal electrocardiogram trial, and from Molndal Hospital. After validation of acid-base samples and TAP, 22,812 cases were accepted for analysis. RESULTS: The median active TAP was 36 min for P0 and 13 min for P>=1 (P<0.001). After adjustments for parity, epidural, labor induction, birth weight, and gender, pushing for 15-29 min (n=6589) relative to pushing for <15 min (n=7264) increased the OR of a cord artery pH of <7.00 to 3.20 (95% CI 1.7-6.0), and that of a base deficit in extracellular fluid of >12 mmol/L to 3.5 (95% CI 1.3-9.0). The group with a cord artery pH of <7.00 had a longer TAP than the group with pH>=7.00: median (5th 95th percentile), 38 (9-107) min vs. 23 (5-87) min, P<0.001. The probability of a spontaneous vaginal delivery decreased significantly with every subsequent increase of 30 min in TAP (P<0.05). CONCLUSION: The risks of severe acidemia, metabolic acidosis, and deteriorated neonatal outcome gradually increased with the length of TAP (>15 min), while the probability of a spontaneous vaginal delivery decreased with the duration of pushing. We suggest active physiological evaluation of the labor progress together with continuous electronic fetal monitoring during pushing irrespective of guideline thresholds. PMID- 22098307 TI - Expression changes of sex hormone binding globulin in GDM placental tissues. AB - OBJECTIVE: To compare the expression of sex hormone binding globulin (SHBG) in normal placental tissues with placental tissues from patients with gestational diabetes mellitus (GDM) and to deduce the mechanism affecting placental SHBG in GDM. METHODS: We detected SHBG localization and measured SHBG mRNA and protein using immunohistochemistry, reverse-transcription polymerase chain reaction, and Western blotting, respectively, in normal and GDM placental tissues. The distribution of SHBG in placental cells was examined using immune electron microscopy. RESULTS: Compared to controls, placental tissues from patients in the GDM group displayed disordered cell surface microvilli that were decreased in quantity, swollen, and had narrowed and broken gap junctions. Intracellular abnormalities included expanded rough endoplasmic reticula, swollen mitochondria, and irregular nuclear morphologies with non-uniform chromatin. SHBG localized primarily to trophoblast cell membranes and cytoplasm. SHBG was strongly expressed on the microvilli side and weakly expressed on the basement membrane with uneven staining. SHBG also was expressed in villous stromal cells and vascular endothelial cells. Compared to the controls, placental tissues from the GDM group displayed significantly decreased immunostaining rates for SHBG, as well as significantly lower levels of SHBG mRNA and protein expression (P<0.05). CONCLUSION: SHBG was detected in placental trophoblast cells from patients with GDM, and the synthesis and secretion of SHBG were reduced when trophoblast cells were irregular. A decrease in SHBG could affect placental function or aggravate GDM. Our results suggest that placental SHBG plays an important role in the pathogenesis of GDM. PMID- 22098308 TI - The impact of hospital mergers on treatment intensity and health outcomes. AB - OBJECTIVE: To analyze the impact of hospital mergers on treatment intensity and health outcomes. DATA: Hospital inpatient data from California for 1990 through 2006, encompassing 40 mergers. STUDY DESIGN: I used a geographic-based IV approach to determine the effect of a zip code's exposure to a merger. The merged facility's market share represents exposure, instrumented with combined premerge shares. Additional specifications include Herfindahl Index (HHI), instrumented with predicted change in HHI. RESULTS: The primary specification results indicate that merger completion is associated with a 3.7 percent increase in the utilization of bypass surgery and angioplasty and a 1.7 percent increase in inpatient mortality above averages in 2000 for the average zip code. Isolating the competition mechanism mutes the treatment intensity result slightly, but it more than doubles the merger exposure effect on inpatient mortality to a 3.9 percent increase. The competition mechanism is associated with a sizeable increase in number of procedures. CONCLUSIONS: Unlike previous studies, this analysis finds that hospital mergers are associated with increased treatment intensity and higher inpatient mortality rates among heart disease patients. Access to additional outcome measures such as 30-day mortality and readmission rates might shed additional light on whether the relationship between these outcomes is causal. PMID- 22098309 TI - Successful management of severe infant bullous pemphigoid with omalizumab. PMID- 22098310 TI - The extremophile Acidithiobacillus ferrooxidans possesses a c-di-GMP signalling pathway that could play a significant role during bioleaching of minerals. AB - AIMS: The primary goal of this study was to characterize the existence of a functional c-di-GMP pathway in the bioleaching bacterium Acidithiobacillus ferrooxidans. METHODS AND RESULTS: A bioinformatic search revealed that the genome sequence of At. ferrooxidans ATCC 23270 codes for several proteins involved in the c-di-GMP pathway, including diguanylate cyclases (DGC), phosphodiesterases and PilZ effector proteins. Overexpression in Escherichia coli demonstrated that four At. ferrooxidans genes code for proteins containing GGDEF/EAL domains with functional DGC activity. MS/MS analysis allowed the identification of c-di-GMP in nucleotide preparations obtained from At. ferrooxidans cells. In addition, c-di-GMP levels in cells grown on the surface of solid energetic substrates such as sulfur prills or pyrite were higher than those measured in ferrous iron planktonic cells. CONCLUSIONS: At. ferrooxidans possesses a functional c-di-GMP pathway that could play a key role in At. ferrooxidans biofilm formation during bioleaching processes. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first global study about the c-di-GMP pathway in an acidophilic bacterium of great interest for the biomining industry. It opens a new way to explore the regulation of biofilm formation by biomining micro organisms during the bioleaching process. PMID- 22098311 TI - Northward shifts of the distributions of Spanish reptiles in association with climate change. AB - It is predicted that climate change will drive extinctions of some reptiles and that the number of these extinctions will depend on whether reptiles are able to change their distribution. Whether the latitudinal distribution of reptiles may change in response to increases in temperature is unknown. We used data on reptile distributions collected during the 20th century to analyze whether changes in the distributions of reptiles in Spain are associated with increases in temperature. We controlled for biases in sampling effort and found a mean, statistically significant, northward shift of the northern extent of reptile distributions of about 15.2 km from 1940-1975 to 1991-2005. The southern extent of the distributions did not change significantly. Thus, our results suggest that the latitudinal distributions of reptiles may be changing in response to climate change. PMID- 22098312 TI - Amelioration of acute graft-versus-host disease by adoptive transfer of ex vivo expanded human cord blood CD4+CD25+ forkhead box protein 3+ regulatory T cells is associated with the polarization of Treg/Th17 balance in a mouse model. AB - BACKGROUND: Human cord blood (CB) is a superior source of regulatory T cells (Tregs) compared with peripheral blood. Initial studies have shown that CB derived Tregs can be effectively expanded ex vivo. However, in vitro suppressor activity of expanded CB-Tregs and their efficacy in the prevention of acute graft versus-host disease (aGVHD) in vivo are poorly understood. STUDY DESIGN AND METHODS: In vitro, human CB CD4+CD25+ T cells expanded with anti-CD3/CD28 beads plus interleukin (IL)-2 and the phenotypes, expression of cytokines, and suppression of expanded cells were analyzed after two cycles of stimulation. In vivo, the addition of human CB-Tregs was transferred in the major histocompatibility complex-mismatched aGVHD mouse model. Survival, body weight, GVHD scoring, histopathologic specimens, serum cytokines, and Th subsets were analyzed in CB-Treg-treated mice and untreated controls. RESULTS: After being expanded ex vivo, human CB-derived Tregs with potent suppressor function could meet clinical demands. Up to 85% of mice with CB-Tregs treatment survived beyond Day 63 after bone marrow transplantation; however, all aGVHD mice died within 18 days. In the serum of the CB-Treg-treated mice, the production of transforming growth factor-beta increased continuously, as opposed to IL-17, which decreased quickly. Consistent with the changes of cytokines, the percentage of mouse CD4+ forkhead box protein 3+ Tregs increased while that of Th17 cells decreased. CONCLUSION: Ex vivo expanded human CB-Tregs significantly prevented allogeneic aGVHD in vivo by modulating various cytokine secretion and polarizing the Treg/Th17 balance toward Treg, which suggests the potential use of expanded CB Tregs as a therapeutic approach for GVHD. PMID- 22098313 TI - Lead-free NaNbO3 nanowires for a high output piezoelectric nanogenerator. AB - Perovskite ferroelectric nanowires have rarely been used for the conversion of tiny mechanical vibrations into electricity, in spite of their large piezoelectricity. Here we present a lead-free NaNbO(3) nanowire-based piezoelectric device as a high output and cost-effective flexible nanogenerator. The device consists of a NaNbO(3) nanowire-poly(dimethylsiloxane) (PDMS) polymer composite and Au/Cr-coated polymer films. High-quality NaNbO(3) nanowires can be grown by hydrothermal method at low temperature and can be poled by an electric field at room temperature. The NaNbO(3) nanowire-PDMS polymer composite device shows an output voltage of 3.2 V and output current of 72 nA (current density of 16 nA/cm(2)) under a compressive strain of 0.23%. These results imply that NaNbO(3) nanowires should be quite useful for large-scale lead-free piezoelectric nanogenerator applications. PMID- 22098314 TI - An audit of anesthetic management and complications of tracheo-esophageal fistula and esophageal atresia repair. AB - BACKGROUND: Many different anesthetic techniques have been suggested for the management of tracheo-oesophageal fistula/oesophageal atresia (TOF/OA) although the incidence of ventilation difficulty is not well known and it is unclear which technique is best in managing this. The aim of our audit was to determine the incidence of ventilation difficulty during repair of TOF/OA. We also recorded the current practice for anesthesia and analgesia in these children as well as the incidence of comorbidities and surgical complications. METHODS: We retrospectively audited cases of TOF/OA repair over a 3-year period in four hospitals, recording demographics, comorbidities, surgical data, postoperative complications, and anesthetic technique, including ventilation difficulty and management strategy. RESULTS: A total of 111 patients were identified with TOF/OA, and 106 patient notes and 101 anesthetic records were found. 42% of patients were premature, and 57.5% had significant comorbidities. Death was most likely in infants with low birth weight and low gestational age at birth and in those with major cardiac comorbidity. A range of techniques were used for induction, maintenance, extubation, and pain control. There were ventilation difficulties recorded at induction in seven patients, and significant desaturations were recorded in 15 patients intraoperatively. CONCLUSIONS: This audit adds to the data already published about incidences of complications and comorbidities associated with TOF/OA repair. Defining anesthetic practice with regard to ventilation and analgesic strategies is important in comparing the adequacy and risk of techniques used. Our audit shows that a range of differing anesthetic techniques are still employed by different anesthetists and institutions and details some of the techniques being used for managing difficult ventilation. PMID- 22098316 TI - In vitro propagation of Candidatus Rickettsia andeanae isolated from Amblyomma maculatum. AB - Candidatus Rickettsia andeanae was identified during an investigation of a febrile outbreak in northwestern Peru (2002). DNA sequencing from two ticks (Amblyomma maculatum, Ixodes boliviensis) collected during the investigation revealed a novel Rickettsia agent with similarity to the spotted fever group rickettsiae. Since then, Candidatus R. andeanae has been detected in A. maculatum ticks collected in the southeastern and southcentral United States, Argentina, and Peru. To date, Candidatus R. andeanae has not been successfully cultivated in the laboratory. We present evidence for the continuous cultivation in three cell lines of Candidatus R. andeanae isolated from an A. maculatum tick (Portsmouth, Virginia). PMID- 22098318 TI - Salicylic acid derivatives: synthesis, features and usage as therapeutic tools. AB - INTRODUCTION: In the field of medicinal chemistry, there is a growing interest in the use of small molecules. Although acetyl salicylic acid is well known for medical applications, little is known about other salicylic acid derivatives, and there is serious lack of data and information on the effects and biological evaluation that connect them. AREAS COVERED: This review covers the synthesis and drug potencies of salicylic acid derivatives. After a brief overview of the information on salicylic acid and its features, a detailed review of salicylic acids as drugs and prodrugs, usage as cyclooxygenase inhibitors, properties in plants, synthesis and recent patents, is developed. EXPERT OPINION: Salicylic acid research is still an important area and innovations continue to arise, which offer hope for new therapeutics in related fields. It is anticipated that this review will guide the direction of long-term drug/nutraceutical safety trials and stimulate ideas for future research. PMID- 22098317 TI - Asymmetric dimethylarginine (ADMA) determines the improvement of hepatic endothelial dysfunction by vitamin E in cirrhotic rats. AB - BACKGROUND: Hepatic endothelial dysfunction (HED), which is caused by decreased hepatic nitric oxide (NO) bioavailability and increased lipid peroxidation, contributes to portal hypertension, which is a characteristic of cirrhosis. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is involved in cirrhosis-related HED and portal hypertension. AIMS: We evaluated the effect of vitamin E treatment on the lipid peroxidation, HED and portal hypertension in cirrhotic rats. METHODS: The common bile duct ligation (BDL)-induced cirrhotic rats were treated orally either with vehicle or with vitamin E for 1 month immediately after BDL. Systemic and portal haemodynamics, the magnitude of the increase in portal pressure induced by volume expansion, HED, oxidative stress, levels of ADMA, various proteins and mRNAs were then measured. RESULTS: In the vitamin E-treated BDL rats, a decrease in portal pressure was associated with an attenuation of the increased portal pressure induced by volume expansion. In isolated and perfused BDL rat livers, the vitamin E treatment significantly inhibited the (paradoxical) vasoconstriction response to methoxamine and acetylcholine (HED), and this was abolished by the presence of NOS. Vitamin E decreased ADMA synthesizing enzyme PRMT1 expression and the level of thiobarbituric acid-reactive substances (TBARS) in the liver, while increasing the levels of hepatic ADMA metabolizing enzyme DDAH2, eNOS, phosphor-eNOS, ADMA level and superoxide dismutase activity. CONCLUSIONS: The administration of vitamin E suppressed hepatic ADMA and oxidative stress in the cirrhotic liver circulation, and therefore increases NO bioavailability, which improved HED and portal hypertension. PMID- 22098319 TI - Nicotinic acetylcholine receptor ligands, a patent review (2006-2011). AB - INTRODUCTION: Nicotinic acetylcholine receptors (nAChRs), pentameric ligand-gated cation channels, are potential targets for the development of therapeutics for a variety of disease states. AREAS COVERED: This article is reviewing recent advances in the development of small-molecule ligands for diverse nAChR subtypes and is a continuation of an earlier review in this journal. EXPERT OPINION: The development of nAChR ligands with preference for alpha4beta2 or alpha7 subtypes for the treatment of central nervous system disorders are in the most advanced developmental stage. In addition, there is a fast growing interest to generate so called PAMs, positive allosteric modulators, to influence the channels' functionalities. PMID- 22098320 TI - Nuclear factor-kappa B inhibitors; a patent review (2006-2010). AB - INTRODUCTION: Nuclear factor (NF)-kappaB, as transcription factor, is linked to the expression of various genes and plays an essential role in immune and inflammatory responses. Abnormal NF-kappaB signaling results in human diseases, such as immune disorders, inflammation and various cancers. Therefore, regulation of NF-kappaB may treat or improve the symptoms in human disorders. AREAS COVERED: This review provides information on recent NF-kappaB inhibitor-related patents from 2006 to 2010. The patents are explained and categorized by mechanism. The reader will gain an understanding of NF-kappaB function and the structure and biological activity of recently developed NF-kappaB inhibitors that may be new drug candidates. EXPERT OPINION: NF-kappaB plays an essential role in the human body and thus regulation of NF-kappaB is very important for the treatment of diseases. Furthermore, patented compounds and peptides are available as lead compounds in drug development studies. PMID- 22098322 TI - Hepatobiliary transporter expression and post-operative jaundice in patients undergoing partial hepatectomy. AB - BACKGROUND AND AIMS: Post-operative hyperbilirubinaemia in patients undergoing liver resections is associated with high morbidity and mortality. Apart from different known factors responsible for the development of post-operative jaundice, little is known about the role of hepatobiliary transport systems in the pathogenesis of post-operative jaundice in humans after liver resection. METHODS: Two liver tissue samples were taken from 14 patients undergoing liver resection before and after Pringle manoeuvre. Patients were retrospectively divided into two groups according to post-operative bilirubin serum levels. The two groups were analysed comparing the results of hepatobiliary transporter [Na taurocholate cotransporter (NTCP); multidrug resistance gene/phospholipid export pump(MDR3); bile salt export pump (BSEP); canalicular bile salt export pump (MRP2)], heat shock protein 70 (HSP70) expression as well as the results of routinely taken post-operative liver chemistry tests. RESULTS: Patients with low post-operative bilirubin had lower levels of NTCP, MDR3 and BSEP mRNA compared to those with high bilirubin after Pringle manoeuvre. HSP70 levels were significantly higher after ischaemia-reperfusion (IR) injury in both groups resulting in 4.5-fold median increase. Baseline median mRNA expression of all four transporters prior to Pringle manoeuvre tended to be lower in the low bilirubin group whereas expression of HSP70 was higher in the low bilirubin group compared to the high bilirubin group. DISCUSSION: Higher mRNA levels of HSP70 in the low bilirubin group could indicate a possible protective effect of high HSP70 levels against IR injury. Although the exact role of hepatobiliary transport systems in the development of post-operative hyper bilirubinemia is not yet completely understood, this study provides new insights into the molecular aspects of post-operative jaundice after liver surgery. PMID- 22098323 TI - Postural stability and occlusal status among Japanese elderly. AB - BACKGROUND: There are still no data available on the relationship between postural stability and occlusal status among the elderly. OBJECTIVES: To examine relationships between postural stability and occlusal status through a cohort study among elderly Japanese. METHOD: Oral examination, occlusal status, postural stability and a questionnaire were conducted and given to 87 community-dwelling Japanese at enrolment. RESULTS: The average occlusal pressure of the female group was statistically higher than the male group while average occlusal pressure and postural stability length were lesser in the group with more remaining teeth. Postural stability area and number of remaining teeth showed statistically significant correlations. Postural stability length was lesser in the group with strong occlusal force. Furthermore, the number of decayed teeth was fewer in the good hygiene group. CONCLUSIONS: This study identified a close relationship between occlusal status and postural stability of Japanese older individuals. Occlusal hypofunction was observed more in those with occlusal problems, and a decrease in their occlusal functions resulted in postural instability. PMID- 22098324 TI - The impact of psychotherapy, pharmacotherapy, and their combination on quality of life in depression. AB - BACKGROUND: Quality of life (QOL) is known to be negatively affected during the course of major depressive disorder. Various studies have documented the benefits of pharmacotherapy or psychotherapy alone on QOL in depression, with few studies examining combined treatment. This review will examine the evidence for the impact of each modality, as well as their combination, on QOL in depression. METHODS: Using the key terms depression, depress*, major depress*, quality of life, antidepressant*, and psychotherapy, MEDLINE and PsycINFO searches were conducted to identify treatment-outcome studies that used known QOL measurements over the past twenty-six years (1984 to 2010). RESULTS: Significant improvements in depressive symptomatology and QOL measurements were found with pharmacotherapy, psychotherapy, and their combination, with some studies showing greater improvement following combined treatment than with either intervention alone. CONCLUSIONS: Substantial evidence suggests that psychotherapy, pharmacotherapy, and their combination have favorable effects on QOL in depression. While some studies have shown that combined therapy is superior than either of the two forms alone in improving QOL, additional research is needed to elucidate this effect. QOL measurement is an important dimension of treatment outcome assessment in patients with depression. PMID- 22098325 TI - Narcissistic interpersonal problems in clinical practice. AB - Pathological narcissism is associated with significant interpersonal problems, which are unlikely to be acknowledged by narcissistic patients as clinical issues. Although a substantial clinical and theoretical literature deals with narcissism, a succinct overview of core narcissistic interpersonal problems is lacking, particularly in terms of their presentation in clinical settings. This article provides a descriptive overview of the major types of interpersonal problems associated with pathological narcissism: dominance, vindictiveness, and intrusiveness. We outline how these problems can manifest in patients' relations with others and in treatment situations. Clinical vignettes are provided to highlight the presentation of narcissistic interpersonal dysfunction in various types of clinical encounters, and to facilitate discussion of treatment implications. PMID- 22098326 TI - When the lightning rod leaves home: a family therapy case characterized by successive generations of familial conflict during a transition into young adulthood. PMID- 22098327 TI - The Tunisian Campaign, war neuroses, and the reorientation of American psychiatry during World War II. PMID- 22098328 TI - Women and aging. PMID- 22098330 TI - Coordination numbers of hydrated divalent transition metal ions investigated with IRPD spectroscopy. AB - Hydration of the divalent transition metal ions, Mn, Fe, Co, Ni, Cu, and Zn, with 5-8 water molecules attached was investigated using infrared photodissociation spectroscopy and photodissociation kinetics. At 215 K, spectral intensities in both the bonded-OH and free-OH stretch regions indicate that the average coordination number (CN) of Mn(2+), Fe(2+), Co(2+), and Ni(2+) is ~6, and these CN values are greater than those of Cu(2+) and Zn(2+). Ni has the highest CN, with no evidence for any population of structures with a water molecule in a second solvation shell for the hexa-hydrate at temperatures up to 331 K. Mn(2+), Fe(2+), and Co(2+) have similar CN at low temperature, but spectra of Mn(2+)(H(2)O)(6) indicate a second population of structures with a water molecule in a second solvent shell, i.e., a CN < 6, that increases in abundance at higher temperature (305 K). The propensity for these ions to undergo charge separation reactions at small cluster size roughly correlates with the ordering of the hydrolysis constants of these ions in aqueous solution and is consistent with the ordering of average CN values established from the infrared spectra of these ions. PMID- 22098332 TI - Effect of bed head elevation during sleep in symptomatic patients of nocturnal gastroesophageal reflux. AB - BACKGROUND AND AIM: Nocturnal gastro-esophageal reflux causes heartburn and sleep disturbances impairing quality of life. Lifestyle modifications, like bed head elevation during sleep, are thought to alleviate the symptoms of gastroesophageal reflux. We tested the hypothesis that bed head elevation might decrease recumbent acid exposure compared to sleeping in a flat bed. METHODS: Patients of symptomatic nocturnal reflux and documented recumbent (supine) reflux verified by esophageal pH test entered the trial. On day 1, baseline pH was measured while the patient slept on a flat bed. Then patients slept on a bed with the head end elevated by a 20-cm block for the next 6 consecutive days from day 2 to day 7. The pH test was repeated on day 2 and day 7. Each patient acted as his own control. RESULTS: Twenty of 24 (83.3%) patients with mean age of 36 +/- 5.5 years completed the trial. The mean (+/- SD) supine reflux time %, acid clearance time, number of refluxes 5 min longer and symptom score on day 1 and day 7 were 15.0 +/ 8.4 and 13.7 +/- 7.2; P = 0.001, 3.8 +/- 2.0 and 3.0 +/- 1.6; P = 0.001, 3.3 +/- 2.2 and 1.0 +/- 1.2; P = 0.001, and 2.3 +/- 0.6 and 1.5 +/- 0.6; P = 0.04, respectively. The sleep disturbances improved in 13 (65%) patients. CONCLUSIONS: Bed head elevation reduced esophageal acid exposure and acid clearance time in nocturnal (supine) refluxers and led to some relief from heartburn and sleep disturbance. PMID- 22098331 TI - Cortical activity patterns predict robust speech discrimination ability in noise. AB - The neural mechanisms that support speech discrimination in noisy conditions are poorly understood. In quiet conditions, spike timing information appears to be used in the discrimination of speech sounds. In this study, we evaluated the hypothesis that spike timing is also used to distinguish between speech sounds in noisy conditions that significantly degrade neural responses to speech sounds. We tested speech sound discrimination in rats and recorded primary auditory cortex (A1) responses to speech sounds in background noise of different intensities and spectral compositions. Our behavioral results indicate that rats, like humans, are able to accurately discriminate consonant sounds even in the presence of background noise that is as loud as the speech signal. Our neural recordings confirm that speech sounds evoke degraded but detectable responses in noise. Finally, we developed a novel neural classifier that mimics behavioral discrimination. The classifier discriminates between speech sounds by comparing the A1 spatiotemporal activity patterns evoked on single trials with the average spatiotemporal patterns evoked by known sounds. Unlike classifiers in most previous studies, this classifier is not provided with the stimulus onset time. Neural activity analyzed with the use of relative spike timing was well correlated with behavioral speech discrimination in quiet and in noise. Spike timing information integrated over longer intervals was required to accurately predict rat behavioral speech discrimination in noisy conditions. The similarity of neural and behavioral discrimination of speech in noise suggests that humans and rats may employ similar brain mechanisms to solve this problem. PMID- 22098333 TI - The procedure of evaluating the practical adhesion strength of new biocompatible nano- and micro-thin films in accordance with international standards. AB - The possibilities of using newly developed nano- and micro-thin films in biomedicine are intensively studied at the present time. Many research institutions are looking for ways to evaluate mechanical properties of these films. One of the most important and frequently studied characteristics is practical adhesion. A very important method for evaluating the practical adhesion strength is scratch test. Often, however, the research teams use a method based on the disunity evaluation of adhesion of biocompatible surface layer. This makes the quantitative comparison of research results impossible. We designed and tested new evaluation method and procedure based on international standards in order to eliminate these problems. This article is aimed at showing the new possibility of using established standards for evaluating adhesion of nano- and micro-thin biocompatible films and at showing the application of the standards to evaluate the often studied DLC biocompatible layers. The thickness of the film was 470 nm. As a substrate a titanium alloy Ti6Al4V was used. PMID- 22098334 TI - The paradox of triple negative breast cancer: novel approaches to treatment. AB - Breast cancer that lacks expression of estrogen/progesterone receptors and overexpression of the human epidermal growth factor receptor2 (HER2), i.e. triple negative breast cancer (TNBC), is not amenable to current targeted therapies and carries a poor prognosis. This review discusses the natural history of TNBC and published literature in the relevant treatment landscape, with a focus on newer therapies. Compared with other subtypes of breast cancer, TN tumors have higher response rates to neoadjuvant chemotherapy; however, this advantage is not clearly translated into the metastatic setting and has not improved these patients' overall survival. Numerous cytotoxic and targeted strategies have demonstrated efficacy or are under investigation. Strategies showing promise in this difficult-to-treat group of patients include cytotoxic therapy with platinum containing agents, ixabepilone, and novel targeted approaches such as poly(ADP ribose) polymerase inhibitors. PMID- 22098335 TI - Unraveling the regulatory network of the MADS box transcription factor RIN in fruit ripening. AB - The MADS box transcription factor RIN is a global regulator of fruit ripening. However, the direct targets modulated by RIN and the mechanisms underlying the transcriptional regulation remain largely unknown. Here we identified 41 protein spots representing 35 individual genes as potential targets of RIN by comparative proteomic analysis of a rin mutant in tomato fruits. Gene expression analysis showed that the mRNA level of 26 genes correlated well with the protein level. After examining the promoter regions of the candidate genes, a variable number of RIN binding sites were found. Five genes (E8, TomloxC, PNAE, PGK and ADH2) were identified as novel direct targets of RIN by chromatin immunoprecipitation. The results of a gel mobility shift assay confirmed the direct binding of RIN to the promoters of these genes. Of the direct target genes, TomloxC and ADH2, which encode lipoxygenase (LOX) and alcohol dehydrogenase, respectively, are critical for the production of characteristic tomato aromas derived from LOX pathway. Further study indicated that RIN also directly regulates the expression of HPL, which encodes hydroperoxide lyase, another rate-limiting enzyme in the LOX pathway. Loss of function of RIN causes de-regulation of the LOX pathway, leading to a specific defect in the generation of aroma compounds derived from this pathway. These results indicate that RIN modulates aroma formation by direct and rigorous regulation of expression of genes in the LOX pathway. Taken together, our findings suggest that the regulatory effect of RIN on fruit ripening is achieved by targeting specific molecular pathways. PMID- 22098336 TI - Extracellular calcium-sensing receptor is critical in hypoxic pulmonary vasoconstriction. AB - AIMS: The initiation of hypoxic pulmonary vasoconstriction (HPV) involves an increase in cytosolic calcium ([Ca(2+)](i)) in pulmonary artery (PA) smooth muscle cells (PASMCs). Both the processes depend on extracellular Ca(2+). Extracellular Ca(2+) can be sensed by extracellular calcium-sensing receptor (CaSR). This study aims at determining whether CaSR is pivotal in the initiation of HPV. RESULTS: Experiments were performed in cultured PASMCs, isolated PAs, and rats including CaSR knockdown preparations. Both hypoxia and H(2)O(2) equivalent to the level achieved by hypoxia increased [Ca(2+)](i) in an extracellular Ca(2+) dependent manner in PASMCs, and this was inhibited by CaSR knockdown or its negative allosteric modulator, Calhex231. Hypoxia-increased H(2)O(2) generation was diminished by mitochondria depletion. Mitochondria depletion abolished hypoxia-induced [Ca(2+)](i) increase (HICI), which was reversed by H(2)O(2) repletion. CaSR knockdown or Calhex231, however, prevented the reversible effect of H(2)O(2). HICI was abolished by catalase-polyethylene glycol (PEG-Catalase), not superoxide dismutase-polyethylene glycol (PEG-SOD) pretreatment, attenuated by ryanodine receptor3-knockdown or inhibition of store-operated Ca(2+) entry. HPV in vitro and in vivo was inhibited by Calhex231 and by CaSR knockdown. INNOVATION: A novel mechanism underlying HPV is revealed by the role of CaSR in orchestrating reactive oxygen species and [Ca(2+)](i) signaling. CONCLUSIONS: The activation of mitochondrial H(2)O(2)-sensitized CaSR by extracellular Ca(2+) mediates HICI in PASMCs and, thus, initiates HPV. PMID- 22098337 TI - The Clavibacter michiganensis subsp. michiganensis-tomato interactome reveals the perception of pathogen by the host and suggests mechanisms of infection. AB - The Gram-positive bacterium Clavibacter michiganensis subsp. michiganensis (Cmm) causes wilt and canker disease of tomato (Solanum lycopersicum). Mechanisms of Cmm pathogenicity and tomato response to Cmm infection are not well understood. To explore the interaction between Cmm and tomato, multidimensional protein identification technology (MudPIT) and tandem mass spectrometry were used to analyze in vitro and in planta generated samples. The results show that during infection Cmm senses the plant environment, transmits signals, induces, and then secretes multiple hydrolytic enzymes, including serine proteases of the Pat-1, Ppa, and Sbt familes, the CelA, XysA, and NagA glycosyl hydrolases, and other cell wall-degrading enzymes. Tomato induction of pathogenesis-related (PR) proteins, LOX1, and other defense-related proteins during infection indicates that the plant senses the invading bacterium and mounts a basal defense response, although partial with some suppressed components including class III peroxidases and a secreted serine peptidase. The tomato ethylene-synthesizing enzyme ACC oxidase was induced during infection with the wild-type Cmm but not during infection with an endophytic Cmm strain, identifying Cmm-triggered host synthesis of ethylene as an important factor in disease symptom development. The proteomic data were also used to improve Cmm genome annotation, and thousands of Cmm gene models were confirmed or expanded. PMID- 22098338 TI - Detection of Acidovorax valerianellae, the causing agent of bacterial leaf spots in corn salad [Valerianella locusta (L.) Laterr.], in corn salad seeds. AB - AIM: The black leaf spot disease on corn salad caused by the bacterium Acidovorax valerianellae has been observed in Europe for several years and causes economic losses in corn salad cropping. Contaminated seeds or infested soil are considered as the major infection sources. The use of healthy seed material is the only way to prevent disease outbreaks. Therefore, a sensitive diagnostic method for seed testing should be developed. METHODS AND RESULTS: Using a triple antibody sandwich ELISA with a high-specific monoclonal antibody, a quick and reliable detection method for contamination of seed lots with the pathogen was developed. This method allowed to detect contaminated seed lots as well as contamination with A. valerianellae in single seeds. Furthermore, the occurrence and distribution of the pathogen could be shown in symptomatic corn salad leaves and in naturally infested seeds by transmission electron microscopy and immunogold labelling for the first time. CONCLUSION: Our results confirm the seed transmission of this corn salad disease. Pathogen load and distribution vary between positively tested seed lots. SIGNIFICANCE AND IMPACT OF THE STUDY: With this method, not only routine testing of seed material to eliminate contaminated seed lots from production is possible but also the control of sanitation procedures to reduce contamination. PMID- 22098339 TI - Botulinum A toxin and brachioradial pruritus. PMID- 22098340 TI - Xenotropic murine leukemia virus-related virus does not pose a risk to blood recipient safety. AB - BACKGROUND: When xenotropic murine leukemia virus-related virus (XMRV) was first reported in association with chronic fatigue syndrome, it was suggested that it might offer a risk to blood safety. Thus, the prevalence of the virus among blood donors and, if present, its transmissibility by transfusion need to be defined. STUDY DESIGN AND METHODS: Two populations of routine blood donor samples (1435 and 13,399) were obtained for prevalence evaluations; samples from a linked donor recipient repository were also evaluated. Samples were tested for the presence of antibodies to XMRV-related recombinant antigens and/or for XMRV RNA, using validated, high-throughput systems. RESULTS: The presence of antibodies to XMRV could not be confirmed among a total of 17,249 blood donors or recipients (0%; 95% confidence interval [CI], 0%-0.017%); 1763 tested samples were nonreactive for XMRV RNA (0%; 95% CI, 0%-0.17%). Evidence of infection was absent from 109 recipients and 830 evaluable blood samples tested after transfusion of a total of 3741 blood components. CONCLUSIONS: XMRV and related murine leukemia virus (MLV) markers are not present among a large population of blood donors and evidence of transfusion transmission could not be detected. Thus, these viruses do not currently pose a threat to blood recipient safety and further actions relating to XMRV and MLV are not justified. PMID- 22098341 TI - An integrated approach for predicting fates of reintroductions with demographic data from multiple populations. AB - We devised a novel approach to model reintroduced populations whereby demographic data collected from multiple sites are integrated into a Bayesian hierarchical model. Integrating data from multiple reintroductions allows more precise population-growth projections to be made, especially for populations for which data are sparse, and allows projections that account for random site-to-site variation to be made before new reintroductions are attempted. We used data from reintroductions of the North Island Robin (Petroica longipes), an endemic New Zealand passerine, to 10 sites where non-native mammalian predators are controlled. A comparison of candidate models that we based on deviance information criterion showed that rat-tracking rate (an index of rat density) was a useful predictor of robin fecundity and adult female survival, that landscape connectivity and a binary measure of whether sites were on a peninsula were useful predictors of apparent juvenile survival (probably due to differential dispersal away from reintroduction sites), and that there was unexplained random variation among sites in all demographic rates. We used the two best supported models to estimate the finite rate of increase (lambda) for populations at each of the 10 sites, and for a proposed reintroduction site, under different levels of rat control. Only three of the reintroduction sites had lambda distributions completely >1 for either model. At two sites, lambda was expected to be >1 if rat tracking rates were <5%. At the other five reintroduction sites, lambda was predicted to be close to 1, and it was unclear whether growth was expected. Predictions of lambda for the proposed reintroduction site were less precise than for other sites because distributions incorporated the full range of site-to-site random variation in vital rates. Our methods can be applied to any species for which postrelease data on demographic rates are available and potentially can be extended to model multiple species simultaneously. PMID- 22098342 TI - Management systems, patient quality improvement, resource availability, and substance abuse treatment quality. AB - OBJECTIVE: To examine the relationships among general management systems, patient focused quality management/continuous process improvement (TQM/CPI) processes, resource availability, and multiple dimensions of substance use disorder (SUD) treatment. DATA SOURCES/STUDY SETTING: Data are from a nationally representative sample of 221 SUD treatment centers through the National Treatment Center Study (NTCS). STUDY DESIGN: The design was a cross-sectional field study using latent variable structural equation models. The key variables are management practices, TQM/continuous quality improvement (CQI) practices, resource availability, and treatment center performance. DATA COLLECTION: Interviews and questionnaires provided data from treatment center administrative directors and clinical directors in 2007-2008. PRINCIPAL FINDINGS: Patient-focused TQM/CQI practices fully mediated the relationship between internal management practices and performance. The effects of TQM/CQI on performance are significantly larger for treatment centers with higher levels of staff per patient. CONCLUSIONS: Internal management practices may create a setting that supports implementation of specific patient-focused practices and protocols inherent to TQM/CQI processes. However, the positive effects of internal management practices on treatment center performance occur through use of specific patient-focused TQM/CPI practices and have more impact when greater amounts of supporting resources are present. PMID- 22098343 TI - Anesthetic and perioperative risk in the patient with Ataxia-Telangiectasia. AB - OBJECTIVES/AIM: To report our relatively large experience with perioperative care for patients with Ataxia-Telangiectasia (A-T) and to identify the nature and frequency of complications. BACKGROUND: Ataxia-Telangiectasia is a rare autosomal recessive genetic disorder resulting in progressive multisystem degeneration and characteristic findings including complex neurodegeneration, immunodeficiency, increased risk of malignancy, and lung disease. Anecdotal reports have suggested high perioperative morbidity in patients with A-T, but few data exist. METHODS/MATERIALS: The Ataxia-Telangiectasia Clinical Center database was cross referenced with operative records between 1995 and 2009 to identify patients with perioperative A-T, and medical records were reviewed for preoperative history, management techniques, and complications. RESULTS: Twenty-one patients with A-T underwent 34 anesthetics during the study period. The median age was 12.5 years (range 6-33 years). Common comorbidities included neurologic (100%), pulmonary (68%), immunologic (50%), oncologic (47%), and gastroenterologic (35%) disorders. Supplemental oxygen was required on postanesthesia care unit discharge for 24% of patients with a maximal duration of 24 h. Although mild postoperative hypothermia was relatively common (44% of anesthetics), there were no major complications, no unplanned admissions, and no mortality in this series. CONCLUSIONS: Although limited by its retrospective nature, this is the first series describing perioperative risk for patients with A-T. Our results indicate that general anesthesia, airway manipulation, and perioperative mechanical ventilation may be tolerated with only minor postoperative anesthetic concerns. Perioperative providers should be aware of the complex multisystem medical concerns that may arise in these patients. PMID- 22098344 TI - Innovations in the treatment of cystic fibrosis: outriders for the treatment of diseases with other genetic defects? PMID- 22098345 TI - Subsystem quantum mechanics and in silico medicinal and biological chemistry. PMID- 22098347 TI - Drug discovery in the 21st century. AB - The Advanced Pharmaceutical Chemistry conference entitled was held on 6-7 June 2011 at the Broad Institute in Cambridge, MA, USA. This 2-day conference focused on four specific areas: applying biophysical techniques to address current challenges in medicinal chemistry and drug discovery; treatment interventions for Alzheimer's disease; drug discovery for orphan, rare and neglected diseases; and kinase drug discovery for chronic and rare diseases. The meeting attracted 80 attendees, approximately 95% of whom were drawn from the local biopharmaceutical industry. PMID- 22098348 TI - Iron chelation: deciphering novel molecular targets for cancer therapy. The tip of the iceberg of a web of iron-regulated molecules. AB - The response of cells to cellular iron depletion is complex with multiple molecules and signaling pathways being involved. Indeed, this is far broader than just the effect on the classical target, ribonucleotide reductase. It is likely that a network of interactions exists between the molecular players and that the relationships currently known only represent the 'tip of an iceberg' in terms of understanding the response of cells to iron deprivation. This article describes some of the research being undertaken in this area by the Richardson group at the University of Sydney, Australia [corrected]. PMID- 22098349 TI - Antiproliferative effect of 1-deamino-8-D-arginine vasopressin analogs on human breast cancer cells. AB - BACKGROUND: Desmopressin (dDAVP), a synthetic nonapeptide derivative of arginine vasopressin, is a safe antidiuretic and hemostatic compound that acts as a selective agonist for the vasopressin V2 membrane receptor (V2R). It is known that dDAVP can inhibit progression of residual metastatic cells in preclinical models. Among other mechanisms, the compound induces an agonist effect on V2R present in tumor cells. RESULTS/DISCUSSION: Looking for novel analogs with improved anti-tumor activity, positions 4 and 5, at the conformational peptide loop, were substituted. The analog [V(4)Q(5)]dDAVP ([4-valine 5-glutamine] desmopressin) exhibited a significantly higher antiproliferative effect than dDAVP in cultures of MCF-7, a V2R-expressing human breast carcinoma cell line. The chiral isomer of this analog and tetrapeptide fragments corresponding to the loop region were also assessed. CONCLUSION: Preclinical evaluation of the anti tumor activity of [V(4)Q(5)]dDAVP in animal models is warranted. PMID- 22098350 TI - Collaboration versus outsourcing: the need to think outside the box. AB - As has been widely reviewed elsewhere, the pharmaceutical industry is experiencing an 'innovation deficit' as evidenced by the decline in new chemical entity output. This decline, compounded by increased costs and regulatory requirements highlights the need to significantly revise strategic options across the drug-discovery spectrum. Within such revision(s), much of the focus has been on outsourcing to reduce, or at least contain, costs, but if the underlying predominance of 'closed collaborations' is not challenged to allow better use of combined knowledge and, thus, move towards a more genuine collaborative process then a 'numbers only' approach will not bring medium-to-long-term survival. There are many problems to confront in evolving new sustainable strategies, a real need to think differently exists and should to be cultivated. This article reviews current outsourcing and collaboration strategies to provide a perspective on how great knowledge sharing could help revise the drug-discovery process. PMID- 22098351 TI - Druggability assessment of protein-protein interfaces. AB - Recent success stories concerning the targeting of protein-protein interactions (PPIs) have led to an increased focus on this challenging target class for drug discovery. This article explores various avenues to assess the druggability of PPIs and describes a druggability decision flow chart, which can be applied to any PPI target. This flow chart not only covers small molecules but also peptidomimetics, peptides and conformationally restricted peptides as potential modalities for targeting PPIs. Additionally, a retrospective analysis of PPI druggability using various computational tools is summarized. The application of a systematic approach as presented in this paper will increase confidence that modulators (e.g., small organic molecules or peptides) can ultimately be identified for a particular target before a decision is made to commit significant discovery resources. PMID- 22098352 TI - Isoform-specific inhibitors of ACATs: recent advances and promising developments. AB - Acyl-CoA:cholesterol acyltransferase (ACAT) is a promising therapeutic target for cardiovascular diseases. Although a number of synthetic ACAT inhibitors have been developed, they have failed to show efficacy in clinical trials. Now, the presence of two ACAT isoforms with distinct functions, ACAT1 and ACAT2, has been discovered. Thus, the selectivity of ACAT inhibitors toward the two isoforms is important for their development as novel anti-atherosclerotic agents. The selectivity study indicated that fungal pyripyropene A (PPPA) is only an ACAT2 specific inhibitor. Furthermore, PPPA proved orally active in atherogenic mouse models, indicating it possessed cholesterol-lowering and atheroprotective activities. Certain PPPA derivatives, semi-synthetically prepared, possessed more potent and selective in vitro activity than PPPA against ACAT2. This review covers these studies and describes the future prospects of ACAT2-specific inhibitors. PMID- 22098353 TI - Drug-permeability and transporter assays in Caco-2 and MDCK cell lines. AB - The human colon adenocarcinoma Caco-2 and Madin-Darby canine kidney epithelial cell lines provide in vitro tools to assess a drug's permeability and transporter interactions during discovery and development. The cells, when cultured on semiporous filters, form confluent monolayers that model the intestinal epithelial barrier for permeability, transporter and drug-interaction assays. The applications of these assays in pharmaceutical research include qualitative prediction and ranking of absorption, determining mechanism(s) of permeability, formulation effects on drug permeability, and the potential for transporter mediated drug-drug interactions. This review focuses on recent examples of Caco-2 and Madin-Darby canine kidney cells assays for drug permeability including transfected and knock-down cells, miniaturization and automation, and assay combinations to better understand and predict intestinal drug absorption. PMID- 22098354 TI - Dynamics, flexibility and ligand-induced conformational changes in biological macromolecules: a computational approach. AB - Biomolecules possess important dynamical properties that enable them to adapt and alternate their conformation as a response to environmental stimuli. Recent advancements in computational resources and methodology allow a higher capability to mimic in vitro conditions and open up the possibility of studying large systems over longer timescales. Here, we describe commonly used computational approaches for studying the dynamic properties of proteins. We review a selected set of simulation studies on ligand-induced changes in the chaperonin GroEL GroES, a molecular folding machine, maltose-binding protein, a prototypical member of the periplasmic binding proteins, and the bacterial ribosomal A-site, focusing on aminoglycoside antibiotic recognition. We also discuss a recent quantitative reconstruction of the binding process of benzamidine and trypsin. These studies contribute to the understanding and further development of the medicinal regulation of large biomolecular systems. PMID- 22098357 TI - Protein candidates for the serodiagnosis of rickettsioses. AB - The laboratory diagnosis of rickettsioses is based on serology (reference method), cell culture and/or molecular tools. However, the main drawback of serology is its incapacity to provide identification of Rickettsiae at the level of species. The aim of this study was to propose the versatile protein markers able to discriminate the patients with murine typhus from those with Mediterranean spotted fever. We have cloned and expressed 20 proteins of Rickettsia prowazekii and Rickettsia rickettsii, respectively, using the GATEWAY approach. These recombinant proteins were screened by ELISA with sera of infected patients with Rickettsia typhi and Rickettsia conorii, respectively. We identified several potential markers which allowed infection due to R. typhi to be discriminated from those due to R. conorii. However, the values of test operating parameters were not sufficient for its 'routine' clinical use. Our diagnostic test requires further optimization for be applied as a point-of-care strategy in the management of patients with suspected cases of rickettsiosis. PMID- 22098358 TI - Use of lasers in dermatology. PMID- 22098355 TI - Advances in HIV microbicide development. AB - There is an urgent need control the spread of the global HIV pandemic. A microbicide, or topical drug applied to the mucosal environment to block transmission, is a promising HIV prevention strategy. The development of a safe and efficacious microbicide requires a thorough understanding of the mucosal environment and its role in HIV transmission. Knowledge of the key events in viral infection identifies points at which the virus might be most effectively targeted by a microbicide. The cervicovaginal and rectal mucosa play an important role in the innate defense against HIV, and microbicides must not interfere with these functions. In this review, we discuss the current research on HIV microbicide development. PMID- 22098359 TI - Mathematical models of laser-induced tissue thermal damage. AB - Laser sources are under increasing study for in vivo tumour ablation. Photo thermal ablation in tissues varies tremendously in governing physical phenomena, depending on wavelength, owing to wide variation in the optical properties of tissues, specifically the dominant chromophore and degree and type of scattering. Once converted into local tissue heating, however, the governing thermodynamic principles remain the same. Observed irreversible thermal alterations range from substantial structural disruption due to steam evolution in high temperature short-term activations to low temperature rise, longer-term initiation of the complex protein cascades that result in apoptosis and/or necroptosis. The usual mathematical model in hyperthermia studies, the thermal isoeffect dose, arising from the relative reaction rate formulation, is not an effective description of the higher temperature effects because multiple processes occur in parallel. The Arrhenius formulation based on the theory of absolute reaction rates is much more useful and descriptive in laser heating since the multiple thermodynamically independent processes may be studied separately. PMID- 22098361 TI - Treatment of leg veins with indocyanine green and lasers investigated with mathematical modelling. AB - PURPOSE: The treatment of leg veins is routinely performed in clinical practice using near infrared (NIR) lasers. However, due to low absorption of NIR light in blood vessels, the clinical results are still suboptimal. The absorption of the NIR light can be significantly increased with intravenous introduction of an indocyanine green (ICG) dye. In this work a mathematical model was used to delineate clinically valid settings for ICG and NIR lasers for the treatment of leg veins. METHODS: A finite element commercial package was used to simulate light propagation and absorption and heat generation in a skin-like geometry. The simulations were conducted for 755 nm and 810 nm light wavelengths, which are emitted by alexandrite and diode lasers, respectively. Five different laser settings, six different vessel diameters (0.1-2 mm) and three ICG concentrations (0, 1 or 2 mg/kg body weight (BW)) were used to calculate the temperature field spatial distribution as a function of time. RESULTS: The diameter of the blood vessels affects the temperature distribution during and following laser irradiation, with and without ICG. Adding 1 or 2 mg/kg bw of ICG will cause significant temperature increase (15-35 degrees C, p <= 0.001) in blood vessels with a diameter of 0.1-1 mm and steep temperature gradients in 1.5-2 mm diameter blood vessels. CONCLUSIONS: Intravenous application of ICG at 1-2 mg/kg may improve coagulation of blood vessels with 0.1-1 mm diameter irradiated with either a diode or alexandrite laser. This should be confirmed with clinical trials in the near future. PMID- 22098360 TI - Model-based planning and real-time predictive control for laser-induced thermal therapy. AB - In this article, the major idea and mathematical aspects of model-based planning and real-time predictive control for laser-induced thermal therapy (LITT) are presented. In particular, a computational framework and its major components developed by authors in recent years are reviewed. The framework provides the backbone for not only treatment planning but also real-time surgical monitoring and control with a focus on MR thermometry enabled predictive control and applications to image-guided LITT, or MRgLITT. Although this computational framework is designed for LITT in treating prostate cancer, it is further applicable to other thermal therapies in focal lesions induced by radio-frequency (RF), microwave and high-intensity-focused ultrasound (HIFU). Moreover, the model based dynamic closed-loop predictive control algorithms in the framework, facilitated by the coupling of mathematical modelling and computer simulation with real-time imaging feedback, has great potential to enable a novel methodology in thermal medicine. Such technology could dramatically increase treatment efficacy and reduce morbidity. PMID- 22098362 TI - MR temperature imaging of nanoshell mediated laser ablation. AB - Minimally invasive thermal therapy using high-power diode lasers is an active area of clinical research. Gold nanoshells (AuNS) can be tuned to absorb light in the range used for laser ablation and may facilitate more conformal tumor heating and sparing of normal tissue via enhanced tumor specific heating. This concept was investigated in a xenograft model of prostate cancer (PC-3) using MR temperature imaging (MRTI) in a 1.5T scanner to characterize the spatiotemporal temperature distribution resulting from nanoparticle mediated heating. Tumors with and without intravenously injected AuNS were exposed to an external laser tuned to 808 nm for 180 sec at 4 W/cm(2) under real-time monitoring with proton resonance frequency shift based MRTI. Microscopy indicated that these nanoparticles (140-150 nm) accumulated passively in the tumor and remained close to the tumor microvasculature. MRTI measured a statistically significant (p < 0.001) increase in maximum temperature in the tumor cortex (mean = 21 +/- 7 degrees C) in +AuNS tumors versus control tumors. Analysis of the temperature maps helped demonstrate that the overall distribution of temperature within +AuNS tumors was demonstrably higher versus control, and resulted in damage visible on histopathology. This research demonstrates that passive uptake of intravenously injected AuNS in PC-3 xenografts converts the tumor vasculature into a potent heating source for nanoparticle mediated ablation at power levels which do not generate significant damage in normal tissue. When used in conjunction with MRTI, this has implications for development and validation of more conformal delivery of therapy for interstitial laser ablations. PMID- 22098363 TI - Heat shock protein expression and temperature distribution in prostate tumours treated with laser irradiation and nanoshells. AB - PURPOSE: Sub-lethal temperature elevations in the tumour incurred during laser cancer therapy can induce heat shock protein (HSP) expression leading to enhanced tumour survival and recurrence. Nanoshells utilised in combination with laser therapy can potentially enable selective heat deposition, greater thermal injury, and diminished HSP expression in the tumour. The study objective was to measure the distribution of temperature and HSP expression in prostate tumours in response to laser therapy alone or with nanoshells to determine if these combinatorial therapies can minimise HSP expression. METHODS: PC3 cells were inoculated in the backs of CB17-Prkd c SCID/J mice and treated with external laser irradiation (wavelength of 810 nm, irradiance of 5 W/cm(2), spot size of 5 mm, and heating duration of 3 min) alone or in combination with gold nanoshells (diameter of 55 nm and outer gold shell thickness of 10 nm) introduced into the tumour 24 h prior to laser treatment. Magnetic resonance temperature imaging was used to measure the distribution of temperature elevation in the tumours during laser treatment. Tumours were sectioned 16 h following laser treatment, stained for Hsp27 and Hsp70, imaged with a confocal microscope, and HSP expression levels were quantified as a function of depth in the tumours. RESULTS: Maximum temperature elevations at the tumour surface were 28 degrees C for laser treatment only and 50 degrees C for laser heating in combination with gold nanoshells. Laser therapy alone caused significant induction of HSP expression in the first few millimeters of the tumour depth, whereas decreasing HSP expression occurred with greater tumour depth. Tumours treated with laser and nanoshells experienced substantial temperatures (73-78 degrees C) at the tumour surface and temperatures greater than 53 degrees C in the first few millimeters which eliminated HSP expression. CONCLUSION: Inclusion of nanoshells in laser therapy can provide a mechanism for enhancing heat deposition capable of eliminating HSP expression within a larger tumour region compared to laser heating alone. PMID- 22098365 TI - Electronic properties and dissociative photoionization of thiocyanates. Part II. Valence and shallow-core (sulfur and chlorine 2p) regions of chloromethyl thiocyanate, CH2ClSCN. AB - A combination of photoelectron spectroscopy and synchrotron based photoelectron photoion coincidence (PEPICO) spectra has been applied to investigate the electronic structure and the dissociative ionization of the CH(2)ClSCN molecule in the valence region. The PES is assigned with the electronic structure calculations at the outer-valence Green's function and symmetry adapted cluster/configuration interaction (SAC-CI) levels offer an explanation of our experimental results. Upon vacuum ultraviolet irradiation the low-lying radical cation, located at 10.39 eV is formed. The molecular ion is observed in the time of-flight mass spectra, together with the CH(2)SCN(+) and CH(2)Cl(+) daughter ions. The total ion yield spectra have been measured in the S 2p and Cl 2p regions and several channels have been determined in dissociative photoionization events for the core-excited species. Thus, by using time-of-flight mass spectrometry and synchrotron radiation the relative abundances of the ionic fragments and their kinetic energy release values were obtained from both PEPICO and photoelectron photoion photoion coincidence spectra. Possible fragmentation processes are discussed and compared with that found for the related CH(3)SCN species. PMID- 22098364 TI - Sensorimotor integration for speech motor learning involves the inferior parietal cortex. AB - Sensorimotor integration is important for motor learning. The inferior parietal lobe, through its connections with the frontal lobe and cerebellum, has been associated with multisensory integration and sensorimotor adaptation for motor behaviors other than speech. In the present study, the contribution of the inferior parietal cortex to speech motor learning was evaluated using repetitive transcranial magnetic stimulation (rTMS) prior to a speech motor adaptation task. Subjects' auditory feedback was altered in a manner consistent with the auditory consequences of an unintended change in tongue position during speech production, and adaptation performance was used to evaluate sensorimotor plasticity and short term learning. Prior to the feedback alteration, rTMS or sham stimulation was applied over the left supramarginal gyrus (SMG). Subjects who underwent the sham stimulation exhibited a robust adaptive response to the feedback alteration whereas subjects who underwent rTMS exhibited a diminished adaptive response. The results suggest that the inferior parietal region, in and around SMG, plays a role in sensorimotor adaptation for speech. The interconnections of the inferior parietal cortex with inferior frontal cortex, cerebellum and primary sensory areas suggest that this region may be an important component in learning and adapting sensorimotor patterns for speech. PMID- 22098366 TI - Surgical approach to pulmonary metastases from breast cancer. AB - One of the main characteristics of breast cancer is its capability to disseminate. Solitary pulmonary metastases from breast cancer occur rarely (0.4%). The aim of this study is to check whether or not the outcome following the surgical treatment of pulmonary metastases in patients with breast cancer is in accordance with the data in the literature and based on it to identify prognostic factors. We have reviewed retrospectively data for 33 patients who underwent 43 curative resections of breast cancer pulmonary metastases between 1997 and 2002 at our department. Potential prognostic factors affecting survival, namely survival after lung metastasectomy, assessed were disease-free interval (DFI), the number and location of lung metastases, the diameter in mm of metastases and the extent of pulmonary resection. The median survival for 33 patients with pulmonary breast cancer metastatic lesions after metastasectomy was 73.2 months. Mean 5-year survival was 54.5%. There was a statistically significant difference in survival time with better prognosis for patients with DFI > 36 months (p = 0.0007), complete metastasectomy (p = 0.0153), unilateral pulmonary metastases (p=0.0267) and for patients who underwent multiple operations (p = 0.0211). In multivariate analysis there was significant influence for long-term prognosis for patients with DFI > 36 months (p = 0.0446) and for complete resection of the metastases (p = 0.0275). Analysis of the survival rates for patients with solitary pulmonary metastasis, with different size of tumors and after different types of pulmonary resection showed no significant differences. It was concluded that resection of lung metastases from breast cancer may offer a significant survival benefit for selected patients. The identified prognostic factor for survival after metastasectomy is DFI longer than 36 months and complete resection of the metastases. In our group of patients, DFI longer than 36 months, unilateral pulmonary metastases and number of operations significantly influenced survival. Also, the results showed that lung metastasectomy by conventional surgery is a safe procedure with low perioperative morbidity and mortality rate. PMID- 22098367 TI - Recognizing and preventing death from compensated cirrhosis in the community. PMID- 22098368 TI - Impairment of cellulose- and cellobiose-degrading soil Bacteria by two acidic herbicides. AB - Herbicides have the potential to impair the metabolism of soil microorganisms. The current study addressed the toxic effect of bentazon and 4-chloro-2 methylphenoxyacetic acid on aerobic and anaerobic Bacteria that are involved in cellulose and cellobiose degradation in an agricultural soil. Aerobic saccharide degradation was reduced at concentrations of herbicides above environmental values. Microbial processes (e.g. fermentations, ferric iron reduction) that were linked to anaerobic cellulose and cellobiose degradation were reduced in the presence of both herbicides at concentrations above and at those that occur in crop field soil. 16S rRNA gene transcript numbers of total Bacteria, and selected bacterial taxa (Clostridia [Group I], Planctomycetaceae, and two uncultivated taxa of Bacteroidetes) decreased more in anoxic than in oxic cellulose supplemented soil microcosms in the presence of both herbicides. Collectively, the results suggested that the metabolism of anaerobic cellulose-degrading Bacteria was impaired by typical in situ herbicide concentrations, whereas in situ concentrations did not impair metabolism of aerobic cellulose- and cellobiose-degrading soil Bacteria. PMID- 22098369 TI - The influence of exercises under isokinetic conditions on heart rate in males aged between 40 and 51. AB - The aim of the study was to estimate changes in heart rate (HR) values in response to the exercise under isokinetic conditions, with defined protocol using three different angular velocities and 2 minute break. The subjects were divided into two groups. The first group contained 18 males aged between 40 and 50, and the second group contained 20 males who were 20-30 years old. The heart rate was monitored before, during and after the strength moment measurement under isokinetic conditions of extensors and flexors of knee joint. The strength moment was measured with an angular velocity of 180 degrees /s, 120 degrees /s and 60 degrees /s. The number of repetitions of extension and flexion of the knee joint was 10 for the angular velocity of 180 degrees /s, 8 for the angular velocity of 120 degrees /s and 5 for the angular velocity of 60 degrees /s. The break between each series of repetitions took 2 minutes. The peak torques for extensors and flexors of both lower extremities were measured. The peak torque and heart rate values increased with a decrease in the preset angular velocity and were lower in the second group. The results were within the norm accepted for submaximal heart rate index in both age groups. PMID- 22098370 TI - Rebound peer review: a viable recourse for aggrieved authors? AB - Scholarly peer review represents the linchpin of academic publishing. Recognized benefits of the peer review system are manifold. Critics raise several valid concerns that deserve attention. Several studies show that the current peer review system lacks robustness and is subject to bias in favor of well established research groups and "mainstream" theories. Hypotheses that harmonize with that of the leaders in the field are more likely to be accepted for publication in prestigious journals than heretic or radical ones. Then, there is the risk posed by the potentially unscrupulous reviewer. Alternatives to traditional peer review have been tried but the outcomes fall much short of expectations. Postreview rejection can be equally frustrating for the author and editor particularly when they are victims of limitations of the blinded forms of review. To provide recourse for authors who felt that their work has been rejected not because of the quality of science but because of the constraints of the peer review system, ARS introduces a rebound track for peer review ( www.liebertpub.com/ars ). The rebound peer review track is a two-tier process that represents a hybrid of partially blinded and open peer review systems. The goal is to make sure that every author has the opportunity to rescue their rejected work which they feel may have been victimized by the glitches of the current peer review system. I invite affected authors to make full use of this experimental mechanism so we know whether the rebound peer review should prevail as a viable recourse. PMID- 22098371 TI - Use of contrast echocardiography to detect displacement of the needle during pericardiocentesis. AB - Bedside pericardiocentesis is a safe and routinely practiced procedure. We report a case in which echocardiography-guided pericardiocentesis was performed urgently for cardiac tamponade. In this case, there was displacement of the periocardiocentesis needle that was only detected by change in the color of aspirated fluid and confirmed by the use of contrast echocardiography. We prescribe the use of routine echocardiographic monitoring during pericardiocentesis to avoid this type of complication. PMID- 22098372 TI - NMR metabolomic analysis of dairy cows reveals milk glycerophosphocholine to phosphocholine ratio as prognostic biomarker for risk of ketosis. AB - Ketosis is a common metabolic disease in dairy cows. Diagnostic markers for ketosis such as acetone and beta-hydroxybutyric acid (BHBA) are known, but disease prediction remains an unsolved challenge. Milk is a steadily available biofluid and routinely collected on a daily basis. This high availability makes milk superior to blood or urine samples for diagnostic purposes. In this contribution, we show that high milk glycerophosphocholine (GPC) levels and high ratios of GPC to phosphocholine (PC) allow for the reliable selection of healthy and metabolically stable cows for breeding purposes. Throughout lactation, high GPC values are connected with a low ketosis incidence. During the first month of lactation, molar GPC/PC ratios equal or greater than 2.5 indicate a very low risk for developing ketosis. This threshold was validated for different breeds (Holstein-Friesian, Brown Swiss, and Simmental Fleckvieh) and for animals in different lactations, with observed odds ratios between 1.5 and 2.38. In contrast to acetone and BHBA, these measures are independent of the acute disease status. A possible explanation for the predictive effect is that GPC and PC are measures for the ability to break down phospholipids as a fatty acid source to meet the enhanced energy requirements of early lactation. PMID- 22098373 TI - Identification of kinase substrates by bimolecular complementation assays. AB - As a consequence of the transient nature of kinase-substrate interactions, the detection of kinase targets, although central for understanding many biological processes, has remained challenging. Here we present a straightforward procedure that relies on the comparison of wild type with activation-loop mutants in the kinase of interest by bimolecular complementation assays. As a proof of functionality, we present the identification and in vivo confirmation of substrates of the major cell-cycle kinase in Arabidopsis, revealing a direct link between cell proliferation and the control of the redox state. PMID- 22098374 TI - Protease-antiprotease imbalance may be linked to potential defects in profilaggrin proteolysis in atopic dermatitis. PMID- 22098375 TI - Rapidly progressive B-cell dominated inflammatory neuropathy and littoral cell angioma of the spleen associated with plasmablastic B-cell lymphoma. PMID- 22098376 TI - How do I implement a hospital-based blood management program? PMID- 22098377 TI - Assessing the effectiveness of marine reserves on unsustainably harvested long lived sessile invertebrates. AB - Although the rapid recovery of fishes after establishment of a marine reserve is well known, much less is known about the response of long-lived, sessile, benthic organisms to establishment of such reserves. Since antiquity, Mediterranean red coral (Corallium rubrum) has been harvested intensively for use in jewelry, and its distribution is currently smaller than its historical size throughout the Mediterranean Sea. To assess whether establishment of marine reserves is associated with a change in the size and number of red coral colonies that historically were not harvested sustainably, we analyzed temporal changes in mean colony diameter and density from 1992 to 2005 within red coral populations at different study sites in the Medes Islands Marine Reserve (established in 1992) and in adjacent unprotected areas. Moreover, we compared colony size in the Medes Islands Marine Reserve, where recreational diving is allowed and poaching has been observed after reserve establishment, with colony size in three other marine protected areas (Banyuls, Carry-le-Rouet, and Scandola) with the enforced prohibition of fishing and diving. At the end of the study, the size of red coral colonies at all sampling sites in the Medes Islands was significantly smaller than predicted by growth models and smaller than those in marine protected areas without fishing and diving. The annual number of recreational dives and the percent change in the basal diameter of red coral colonies were negatively correlated, which suggests that abrasion by divers may increase the mortality rates of the largest red coral colonies within this reserve . Our study is the first quantitative assessment of a poaching event, which was detected during our monitoring in 2002, inside the marine reserve. Poaching was associated with a loss of approximately 60% of the biomass of red coral colonies. PMID- 22098378 TI - High-level resistance to gentamicin: genetic transfer between Enterococcus faecalis isolated from food of animal origin and human microbiota. AB - AIMS: To investigate the in vivo gene transfer of high-level gentamicin resistance (HLRG) from Enterococcus faecalis isolated from the food of animal origin to a human isolate, using a mouse model of intestinally colonized human microbiota. METHODS AND RESULTS: In vitro study: The presence of plasmids involved in HLRG coding was investigated. After the conjugation experiment, the recipient strain, Ent. faecalis JH2-SS, acquired a plasmid responsible for HLRG [minimal inhibitory concentration (MIC) >800 MUg ml(-1) ], in a similar position to the donor cells. In vivo study: Seven BALB/c mice were dosed with ceftriaxone (400 mg kg(-1) ) and then inoculated with a dilution of 1/100 of human faeces (HFc). After 72 h, Ent. faecalis JH2-SS (recipient) was inoculated and then, after a further 72 h, the animals were given Ent. faecalis CS19, isolated from the food of animal origin, involved in HLRG (donor). The presence of transconjugant strains in HFc was subsequently recorded on a daily basis until the end of the experiment. The clonal relationship between Ent. faecalis and Escherichia coli in faeces was assessed by RAPD-PCR. Both the in vitro and in vivo studies showed that the receptor strain acquired a plasmid responsible for HLRG (MICs >800 MUg ml(-1) ), which migrated with a similar relative mobility value. Transconjugant strains were detected from 24 h after the donor strain inoculation and persisted until the end of the experiment. CONCLUSIONS: The in vivo gene transfer of HLRG from Ent. faecalis strains, isolated from the food of animal origin, to human microbiota has been demonstrated in a mouse model. SIGNIFICANCE AND IMPACT OF THE STUDY: The complexity found on the therapeutic responses of invasive infectious diseases caused by Ent. faecalis facilitates the assessment of food of animal origin as a resistant pathogen reservoir. In addition, this study may contribute to the understanding of antimicrobials' resistance gene transfer between Ent. faecalis strains from food and human GI tract. PMID- 22098379 TI - Bottom-up photonic crystal lasers. AB - The directed growth of III-V nanopillars is used to demonstrate bottom-up photonic crystal lasers. Simultaneous formation of both the photonic band gap and active gain region is achieved via catalyst-free selective-area metal-organic chemical vapor deposition on masked GaAs substrates. The nanopillars implement a GaAs/InGaAs/GaAs axial double heterostructure for accurate, arbitrary placement of gain within the cavity and lateral InGaP shells to reduce surface recombination. The lasers operate single-mode at room temperature with low threshold peak power density of ~625 W/cm2. Cavity resonance and lasing wavelength is lithographically defined by controlling pillar pitch and diameter to vary from 960 to 989 nm. We envision this bottom-up approach to pillar-based devices as a new platform for photonic systems integration. PMID- 22098380 TI - Isoflavone composition and antioxidant capacity of modified-lipoxygenase soybeans grown in Maryland. AB - Maryland-grown soybean lines modified for low lipoxygenase-1 (LOX-1) content and a traditional nonmodified cultivar were analyzed for fatty acid composition, total phenolic content (TPC), isoflavone composition, relative DPPH* scavenging capacity (RDSC), and hydroxyl radical scavenging capacity (HOSC). Soybean lines included black, brown, and yellow soybeans. TPC of all soybean lines ranged from 2.84 to 4.74 mg gallic acid equiv (GAE)/g flour. Total isoflavones were between 2.78 and 8.66 MUmol/g flour. RDSC of all lines was between 0.48 and 14.62 MUmol Trolox equiv (TE)/g flour, and HOSC ranged from 53.57 to 135.52 MUmol TE/g flour. Some modified-LOX genotypes demonstrated antioxidant capacity and/or isoflavone content similar to or higher than those of the nonmodified cultivar (P < 0.05). Black soybeans demonstrated higher TPC and RDSC than most yellow soybean lines, although they did not have higher isoflavone content. The results demonstrate that modification of the LOX trait did not necessarily alter the antioxidant capacity or chemical composition of the experimental soybean lines when compared with a nonmodified cultivar. These soybean lines may be studied further for nutraceutical properties and use in functional foods. PMID- 22098381 TI - Invariant natural killer T cells in chronic obstructive pulmonary disease. AB - BACKGROUND AND OBJECTIVE: Invariant natural killer T (iNKT) cells may play an important role in regulating the innate and acquired immune systems in chronic obstructive pulmonary disease (COPD). However, there is little information regarding the potential role of iNKT cells in the pathogenesis of COPD. To investigate whether iNKT cells have an important role in COPD, the frequency of iNKT cells in peripheral blood of patients with COPD was analysed. METHODS: This was a comparative study of 28 patients with COPD and 19 age-matched healthy control subjects. Blood iNKT cells were stained with 6B11 mAb, anti-T cell receptor Valpha24 mAb, anti-T cell receptor Vbeta11 mAb or alpha galactosylceramide-loaded CD1d-tetramer, and analysed by flow cytometry. RESULTS: The frequency of CD4(+) 6B11(+) iNKT, CD4(+) Valpha24(+) iNKT, CD4(+) Vbeta11(+) iNKT and CD3(+) 6B11(+) iNKT cells was significantly lower in peripheral blood of patients with COPD than in that of healthy control subjects. The frequency of CD4(+) 6B11(+) iNKT cells was significantly lower in patients with exacerbations of COPD compared with those with stable COPD. CONCLUSIONS: The frequency of iNKT was decreased in peripheral blood of patients with COPD. These results strongly suggest that iNKT cells may play an important role in the pathogenesis of COPD. PMID- 22098382 TI - Hepatitis C virus nonstructural protein specific T cells are associated with virological responses to combination therapy in chronic HCV patients. AB - BACKGROUND: Virus-specific T-cell responses play a major role in antiviral immune response. However, the effect of hepatitis C virus (HCV)-specific T-cell responses on combination therapy still remains controversial. AIMS: To identify the association between HCV-specific T cell responses and efficiency of combination therapy. METHODS: To address this issue, a longitudinal analysis of HCV-specific T-cell responses to overlapping peptides covering HCV-nonstructural protein (NS) was performed using ELISpot assay in 48 chronically infected HCV-1b patients during combination treatment with peginterferon-alfa and ribavirin. RESULTS: Fifty-two percent of chronic HCV patients showed detectable HCV-NS3, NS4 or NS5A specific T-cell responses before therapy, with NS3 appearing to be the most immunodominant protein followed by NS5A and NS4. In addition, the percentage of patients responding to peptide stimulation was higher in patients with sustained virological response (SVR) when compared with those without SVR. Dynamics of HCV-NS-specific T-cell responses were further analysed; we found that HCV-specific T-cell responses maintained higher levels at 12 weeks into treatment in patients with SVR. In contrast, HCV-specific T-cell responses in patients without SVR declined significantly at 4 weeks into treatment and maintained low levels at 12 weeks. CONCLUSION: We found that the HCV-specific T-cell responses were associated with good viral control in patients with combination therapy. PMID- 22098383 TI - Effect of a static magnetic field on nanodosimetric quantities in a DNA volume. AB - PURPOSE: With the advent of magnetic resonance imaging (MRI)-guided radiation therapy it is becoming increasingly important to consider the potential influence of a magnetic field on ionising radiation. This paper aims to study the effect of a magnetic field on the track structure of radiation to determine if the biological effectiveness may be altered. METHODS: Using the Geant4-DNA (GEometry ANd Tracking 4) Monte Carlo simulation toolkit, nanodosimetric track structure parameters were calculated for electrons, protons and alpha particles moving in transverse magnetic fields up to 10 Tesla. Applying the model proposed by Garty et al., the track structure parameters were used to derive the probability of producing a double-strand break (DSB). RESULTS: For simulated primary particles of electrons (200 eV-10 keV), protons (300 keV-30 MeV) and alpha particles (1-9 MeV) the application of a magnetic field was shown to have no significant effect (within statistical uncertainty limits) on the parameters characterizing radiation track structure or the probability of producing a DSB. CONCLUSIONS: The null result found here implies that if the presence of a magnetic field were to induce a change in the biological effectiveness of radiation, the effect would likely not be due to a change in the track structure of the radiation. PMID- 22098385 TI - Bibliometric awareness in nursing scholarship: can we afford to ignore it any longer? AB - In contemporary nursing academia, it is unthinkable that topics such as research methods, evidence-based practice, and the translation of research into practice would be omitted from nursing curricula at any level. What is surprising, however, is that despite a broad educational emphasis on "teaching research", the rising importance of bibliometrics appears to have been largely neglected. If nursing scholarship and nursing scholars are to prosper in the highly competitive field of modern health research, a sophisticated understanding of citation-based methods is clearly required. Armed with this knowledge, one can more successfully argue why scarce research funding, that might otherwise be channeled elsewhere, ought to be assigned to nursing researchers. We hereby urge readers to reflect on the extent to which bibliometrics is covered within formal nursing curricula at their college or university. It is no longer a case of if a graduate nurse will need this skill set for their future professional development, but when. PMID- 22098384 TI - Nursing home work environment and the risk of pressure ulcers and incontinence. AB - OBJECTIVE: To examine the association between nursing home (NH) work environment attributes such as teams, consistent assignment and staff cohesion, and the risk of pressure ulcers and incontinence. DATA SOURCES/SETTING: Minimum dataset for 46,044 residents in 162 facilities in New York State, for June 2006-July 2007, and survey responses from 7,418 workers in the same facilities. STUDY DESIGN: For each individual and facility, primary and secondary data were linked. Random effects logistic models were used to develop/validate outcome measures. Generalized estimating equation models with robust standard errors and probability weights were employed to examine the association between outcomes and work environment attributes. Key independent variables were staff cohesion, percent staff in daily care teams, and percent staff with consistent assignment. Other facility factors were also included. PRINCIPAL FINDINGS: Residents in facilities with worse staff cohesion had significantly greater odds of pressure ulcers and incontinence, compared with residents in facilities with better cohesion scores. Residents in facilities with greater penetration of self-managed teams had lower risk of pressure ulcers, but not of incontinence. Prevalence of consistent assignment was not significantly associated with the outcome measures. CONCLUSIONS: NH environments and management practices influence residents' health outcomes. These findings provide important lessons for administrators and regulators interested in promoting NH quality improvement. PMID- 22098386 TI - Energy relaxation dynamics of the hydration complex of hydroxide. AB - We use polarization-resolved mid-infrared pump-probe spectroscopy to study the dynamics of the hydration shells of hydroxide ions (OH(-)). We excite the OH stretch vibrations of H(2)O molecules solvating the OH(-) ion and observe that this excitation decays with a relaxation time constant T(1) of 200 fs. This relaxation is followed by a thermalization process that becomes slower with increasing concentration of OH(-). The prethermalized state is observed to be anisotropic, showing that the energy of the excited OH stretch vibrations is dissipated within the hydration complex. The anisotropy of the prethermalized state decays both as a result of the reorientation of the OH(-) hydration complex and heat diffusion from the excited complexes to unexcited complexes. Modeling the anisotropy data at different concentrations allows for an accurate estimate of the number of water molecules in the hydration shell of OH(-), the reorientation dynamics of the OH(-) hydration complex, and the molecular-scale heat diffusivity. PMID- 22098387 TI - High-dose esomeprazole is required for intraesophageal acid control in gastroesophageal reflux disease patients with hiatus hernia. AB - BACKGROUND AND AIM: The aim of this study was to assess whether the efficacy of proton pump inhibitors (PPI) therapy at a standard dose in esophageal acid control is affected by the presence of hiatus hernia in Chinese gastroesophageal reflux disease patients, and whether a higher dose of PPI is required for acid control. METHODS: Consecutive gastroesophageal reflux disease patients who had typical reflux symptoms and abnormal baseline 24-h esophageal pH and underwent upper endoscopy were enrolled to receive esomeprazole at 40 mg once daily for 4 weeks. Patients underwent the dual-channel 24-h pH test at the end of 4-week therapy. If the 24-h esophageal pH was still abnormal at the end of 4-week therapy, then esomeprazole at 40 mg twice daily was given for another 4 weeks after a washout interval of 1 week, and a 24-h pH test was repeated at the end of the therapy. RESULTS: Overall, 76 patients were included, 13 with hiatus hernia. Of the 76 patients treated with a 40 mg of esomeprazole daily, esophageal acid exposure was normalized in 64 (84.2%). Normalization of acid exposure was achieved by standard PPI therapy in 53.2% (7/13) of patients with hiatus hernia and 90.5% (57/63) of those without (P = 0.004). A double dose of esomeprazole was successful in normalizing the esophageal pH in all 12 non-responders to the standard dose of esomeprazole, including the six patients with hiatus hernia and six patients without. CONCLUSIONS: The standard-dose of esomeprazole fails to normalize the esophageal pH in almost 50% of patients with hiatus hernia, in whom the "double-dose" esomeprazole therapy is required. PMID- 22098388 TI - Thirteen novel deoxynivalenol-degrading bacteria are classified within two genera with distinct degradation mechanisms. AB - The mycotoxin deoxynivalenol (DON), a secondary metabolite produced by species of the plant pathogen Fusarium, causes serious problems in cereal crop production because of its toxicity towards humans and livestock. A biological approach for the degradation of DON using a DON-degrading bacterium (DDB) appears to be promising, although information about DDBs is limited. We isolated 13 aerobic DDBs from a variety of environmental samples, including field soils and wheat leaves. Of these 13 strains, nine belonged to the Gram-positive genus Nocardioides and other four to the Gram-negative genus Devosia. The degradation phenotypes of the two Gram types were clearly different; all washed cells of the 13 strains degraded 100 MUg mL(-1) DON to below the detection limit (0.5 MUg mL( 1)), but the conditions inducing the DON-degrading activities differed between the two Gram types. The HPLC profiles of the DON metabolites were also distinct between the two genera, although all strains produced 3-epi-deoxynivalenol. The Gram-positive strains showed DON assimilation in media containing DON as a carbon source, whereas the Gram-negatives did not. Our results suggest that aerobic DDBs are distributed within at least two phylogenetically restricted genera, suggesting independent evolution of the DON-degradation mechanisms. PMID- 22098389 TI - The addition of internists to a breast health program. AB - With the increases in complexity of care for breast health concerns, there is a growing need for efficient and effective clinical evaluation, especially for vulnerable populations at risk for poor outcomes. The Breast Health Center at Boston Medical Center is a multidisciplinary program, with internists providing care alongside breast surgeons, radiologists, and patient navigators. Using a triage system previously shown to have high provider and patient satisfaction, and the ability to provide timely care, patients are assigned to either a breast surgeon or internist. From 2007 to 2009, internists cared for 2,408 women, representing half of all referrals. Women served were diverse in terms of race (33% black, 30% Hispanic, 5% Asian), language (34% require language interpreter), and insurance status (51% had no insurance or public insurance). Most presented with an abnormal screen (breast examination 54% or imaging 4%) while the remainder were seen for symptoms such as pain (26%), non-bloody nipple discharge (4%), or risk assessment (7%). A majority of final diagnoses were made through clinical evaluation alone (n = 1,760, 73%), without the need for additional diagnostic imaging or tissue sampling; 9% (n = 214) received a benign diagnosis with the aid of breast imaging; 19% (n = 463) required tissue sampling. Only 4% went on to see a breast surgeon. Internists diagnosed 15 incident cancers with a median time to diagnosis of 19 days. Patient and provider satisfaction was high. These data suggest that a group of appropriately trained internists can provide quality breast care to a vulnerable population in a multidisciplinary setting. Replication of this model requires the availability of more clinical training programs for non-surgical providers. PMID- 22098390 TI - Evaluation of clinical specimens for Rickettsia, Bartonella, Borrelia, Coxiella, Anaplasma, Franciscella and Diplorickettsia positivity using serological and molecular biology methods. AB - We monitored clinical samples from patients of different age groups from selected regions in Slovakia. Overall seroprevalence evaluated by immunofluorescence (IFA) using nine Bartonella, two Borrelia, six rickettsial (spotted fever and typhus group), two Coxiella, and one human granulocytic ehrlichiosis Anaplasma, Franciscella tularensis and Diplorickettsia massiliensis antigens, in rural and city populations of Slovak Republic, was found to be 32% positive for spotted fever group rickettsiae. Only five (10%) of the rickettsia-positive cases evaluated by IFA were confirmed by polymerase chain reaction. Rickettsia helvetica, Rickettsia slovaca, and Rickettsia raoultii infection appear to be prevalent in Slovakia. Furthermore, Coxiella burnetii, Borrelia and, for the first time, Bartonella elisabethae were confirmed in Slovakia. PMID- 22098392 TI - Cerebellopontine angle metastasis of a parotid mucoepidermoid carcinoma arising from perineural invasion along the facial nerve. AB - A 72-year-old male was referred with left sided hearing loss, tinnitus and disequilibrium with radiological appearances suggestive of an intracanalicular left vestibular schwannoma. The patient then developed left sided trigeminal nerve sensory loss over the next 9 months with an enlarging parotid swelling. The eventual diagnosis was a destructive lesion in the left cerebellopontine angle (CPA) arising from metastatic perineural invasion along the facial nerve by a parotid mucoepidermoid carcinoma. Surgical resection and targeted beam radiotherapy achieved a survival period of 9 months. PMID- 22098393 TI - Comparison of CT perfusion parameters and microvessel density in intracranial hemangiopericytomas with peritumoral edema. AB - PURPOSE: Intracranial hemangiopericytomas (HPCs) are rare, and they have a tendency for local recurrence and metastases. The purpose of this study was to evaluate the relationship between CT perfusion (CTP) parameters and microvessel density (MVD) of HPCs and compare CTP parameters in parenchyma and peritumoral edema of HPCs. MATERIALS AND METHODS: The study was approved by the ethics committee, and written informed consent was obtained. Ten patients with HPCs and peritumoral edema, confirmed by pathological results, received 64-slice CT perfusion imaging before operation. To evaluate vascular attenuation of tumoral parenchyma, we immunostained the specimen sections for CD-34, measured the integrated optical density of all the positive stained CD-34 cells in the microscopic field, and calculated its ratio to total area of field as MVD. Perfusion analysis was calculated using the Patlak method. Using a 1-cm distance from the outer enhancing tumor margin as a boundary, the peritumoral edema was divided into an immediate and a distant part. The quantitative CTP parameters, including cerebral blood volume (CBV), permeability-surface area product (PS) of parenchyma, and immediate and distant peritumoral edemas, were compared. CBV and PS in parenchyma and immediate and distant peritumoral edemas of HPCs were also compared to their respective contralateral normal white matter. The correlations between MVD, CBV, and PS of tumoral parenchyma were analyzed. RESULTS: Positive correlations existed between CBV and MVD, PS and MVD (P < 0.05) respectively in the 10 patients. Furthermore, the values of CBV and PS in parenchyma of HPCs were significantly higher than those of the contralateral normal white matter and peritumoral edema (P < 0.05). The value of CBV in peritumoral edema of HPCs were lower than that of contralateral normal white matter (P < 0.05), while the value of PS in immediate and distant peritumoral edemas of HPCs were not significantly difference with that of contralateral normal white matter (P > 0.05). Finally, the values of CBV and PS did not show a significant difference between immediate and distant peritumoral edemas. CONCLUSIONS: CT perfusion imaging, especially determination of maximal CBV and corresponding PS values in the parenchyma, may be a useful and non-invasive technique for the preoperative evaluation of hemodynamic features of HPCs with peritumoral edema. CBV of peritumoral edema indicate that HPCs have a possibility of infiltration, this need further radiological-pathological research. PMID- 22098394 TI - Successful treatment of cutaneous venous malformations in a patient with blue rubber bleb naevus syndrome by Nd:YAG laser. PMID- 22098391 TI - The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1. AB - The transcription factor Nkx2-1 belongs to the homeobox-encoding family of proteins that have essential functions in prenatal brain development. Nkx2-1 is required for the specification of cortical interneurons and several neuronal subtypes of the ventral forebrain. Moreover, this transcription factor is involved in migratory processes by regulating the expression of guidance molecules. Interestingly, Nkx2-1 expression was recently detected in the mouse brain at postnatal stages. Using two transgenic mouse lines that allow prenatal or postnatal cell type-specific deletion of Nkx2-1, we show that continuous expression of the transcription factor is essential for the maturation and maintenance of cholinergic basal forebrain neurons in mice. Notably, prenatal deletion of Nkx2-1 in GAD67-expressing neurons leads to a nearly complete loss of cholinergic neurons and parvalbumin-containing GABAergic neurons in the basal forebrain. We also show that postnatal mutation of Nkx2-1 in choline acetyltransferase-expressing cells causes a striking reduction in their number. These degenerative changes are accompanied by partial denervation of their target structures and results in a discrete impairment of spatial memory. PMID- 22098395 TI - The interaction between seaweed farming as an alternative occupation and fisher numbers in the central Philippines. AB - Alternative occupations are frequently promoted as a means to reduce the number of people exploiting declining fisheries. However, there is little evidence that alternative occupations reduce fisher numbers. Seaweed farming is frequently promoted as a lucrative alternative occupation for artisanal fishers in Southeast Asia. We examined how the introduction of seaweed farming has affected village level changes in the number of fishers on Danajon Bank, central Philippines, where unsustainable fishing has led to declining fishery yields. To determine how fisher numbers had changed since seaweed farming started, we interviewed the heads of household from 300 households in 10 villages to examine their perceptions of how fisher numbers had changed in their village and the reasons they associated with these changes. We then asked key informants (people with detailed knowledge of village members) to estimate fisher numbers in these villages before seaweed farming began and at the time of the survey. We compared the results of how fisher numbers had changed in each village with the wealth, education, seaweed farm sizes, and other attributes of households in these villages, which we collected through interviews, and with village-level factors such as distance to markets. We also asked people why they either continued to engage in or ceased fishing. In four villages, respondents thought seaweed farming and low fish catches had reduced fisher numbers, at least temporarily. In one of these villages, there was a recent return to fishing due to declines in the price of seaweed and increased theft of seaweed. In another four villages, fisher numbers increased as human population increased, despite the widespread uptake of seaweed farming. Seaweed farming failed for technical reasons in two other villages. Our results suggest seaweed farming has reduced fisher numbers in some villages, a result that may be correlated with socioeconomic status, but the heterogeneity of outcomes is consistent with suggestions that alternative occupations are not a substitute for more direct forms of resource management. PMID- 22098397 TI - An investigation of strong sodium retention mechanisms in nanopore environments using nuclear magnetic resonance spectroscopy. AB - Recent experimental research into the adsorption of various cations on zeolite minerals has shown that nanopore channels of approximately 0.5 nm or less can create an effect whereby the adsorption of ions, especially those that are weakly hydrated, can be significantly enhanced. This enhanced adsorption occurs due to the removal of hydrating water molecules which in turn is caused by the nanopore channel's small size. A new adsorption model, called the nanopore inner-sphere enhancement (NISE) effect, has been proposed that explains this unusual adsorption mechanism. To further validate this model a series of nuclear magnetic resonance (NMR) spectroscopy studies is presented here. NMR spectra were gathered for Na adsorbed on three zeolite minerals of similar chemical composition but differing nanoporosities: zeolite Y with a limiting dimension of 0.76 nm, ZSM-5 with a limiting dimension of 0.51 nm, and mordenite with a limiting dimension of 0.26 nm. The NMR experiments validated the predictions of the NISE model whereby Na adsorbed via outer-sphere on zeolite Y, inner-sphere on ZSM-5, and a combination of both mechanisms on mordenite. The strong Na adsorption observed in these nanoporous minerals conflicts with sodium's general designation as a weak electrolyte. PMID- 22098396 TI - Analysis of 120 pediatric patients with nonmalignant disorders transplanted using unrelated plasma-depleted or -reduced cord blood. AB - BACKGROUND: Unrelated cord blood (CB) is an important stem cell source for unrelated hematopoietic cell transplantation (HCT) of patients with nonmalignant disorders. Processing methods to prepare red blood cell-reduced CB units incur significant nucleated cell loss. In contrast, plasma depletion or reduction (PDR) processing of CB units entails the removal of only a portion of the plasma with minimal nucleated cell loss. However, there are relatively limited data regarding outcomes of CB transplants using units processed by PDR. STUDY DESIGN AND METHODS: A Center for International Blood and Marrow Transplant Research (CIBMTR) audited analysis was performed on 120 pediatric patients with nonmalignant disorders transplanted between November 2001 and January 2008 at 29 US and 17 international centers using PDR CB units from two CB banks. RESULTS: Transplant characteristics were as follows: median age, 3.5 years (range, 0.1-14 years); median patient weight, 15 kg (range, 4-61 kg); 58% male; HLA matches (intermediate-resolution HLA-A and HLA-B and high-resolution HLA-DRB1) of the units used in these patients six of six in 26, five of six in 48, four of six in 47, and three of six or two of six in 6; median prefreeze total nucleated cell dose, 10.5*10(7)/kg; median prefreeze CD34+ dose, 3.7*10(5)/kg; and nonmyeloablative regimen in 24%. The median times to myeloid and platelet engraftment were 21 and 49 days, respectively. The cumulative incidence of reported Grade II to IV acute graft-versus-host disease (aGVHD) was 38+/-5%, and 19+/-4% had Grade III to IV aGVHD. The Kaplan-Meier estimates of 3-year transplant-related mortality, overall survival, and disease-free survival were 20+/-4, 79+/-4, and 70+/-6%, respectively. CONCLUSION: These data demonstrate the effectiveness of PDR CB units for HCT. PMID- 22098398 TI - Should cirrhosis change our attitude towards treating non-hepatic cancer? AB - Cirrhosis is a major cause of morbidity and mortality and is the end stage of any chronic liver disease. Cancer, a leading cause of death worldwide, is a growing global health issue. There are limited data in the literature on the incidence, prevalence and management of non-hepatic cancers (NHC) in cirrhotic patients. The aim of this brief review was to underline the main concerns, pitfalls and warnings regarding practice for these patients. Survival of patients with compensated cirrhosis is significantly longer than that of decompensated cirrhosis and patients with NHC and in Child-Pugh class C should not be candidates for cytotoxic chemotherapy. It is important before starting cytotoxic chemotherapy to assess the aetiology and stage of liver disease and to screen these patients for portal hypertension and fluid retention. During cytotoxic chemotherapy, the effectiveness of cancer treatment, as well the appearance of early signs of hepatic decompensation, must be thoroughly monitored. Future phase 3 trial designs in oncology should include a share of patients with compensated cirrhosis to obtain specific information in this setting. Identification of tests able to measure the global degree of hepatic impairment caused by cirrhosis could help in the management of this particular clinical situation. PMID- 22098399 TI - Role of left ventricular dyssynchrony in predicting remodeling after ST elevation myocardial infarction. AB - BACKGROUND: Intraventricular dyssynchrony is associated with worsening systolic function, adverse remodeling, and clinical events. The aim of this study is to investigate whether intraventricular dyssynchrony assessed by tissue Doppler imaging (TDI) can predict left ventricular (LV) remodeling after first ST segment elevation myocardial infarction (STEMI) treated successfully with primary percutaneous coronary intervention (pPCI). METHODS: Fifty-two consecutive patients who presented with first acute STEMI were included in the study. All patients underwent successful pPCI. Standard echocardiography was performed within 48 hours of admission. LV dyssynchrony was assessed by color-coded TDI. Dyssynchrony (Ts-diff) was calculated by maximal temporal difference between time to peak systolic velocities (Ts) of six basal segments. Echocardiographic examination was repeated after 6 months to reassess LV volumes. LV remodeling was defined as >15% increase in LV end-systolic volume index (LVESVI) after 6 months. RESULTS: Eleven patients (23%) developed LV remodeling. Baseline dyssynchrony was found to be correlated with percent change in LVESVI and LV end-diastolic volume index (LVEDVI) after 6 months. Ts-diff, creatine kinase-MB and mitral inflow E wave deceleration time (DT) were the independent predictors of remodeling after STEMI in multivariate logistic regression analysis. Receiver operating characteristic curve analysis showed that Ts-diff >56 msec had 72.7% sensitivity and 83.8% specificity for predicting remodeling. CONCLUSIONS: LV dyssynchrony is a strong predictor of LV remodeling after acute myocardial infarction (AMI). It could be useful in risk stratification of patients after AMI. PMID- 22098400 TI - Evaluation of dynamic formation of cervical spine column based on functional radiological studies in patients after cervical spine injury. AB - The purpose of this study was to evaluate cervical spine function, based on our own functional method of roentgenometric analysis in patients who suffered from cervical spine sprain injury. Study involved 72 patients who suffered from cervical spine whiplash injury. Conventional plain radiographs in all patients included three lateral views: maximum flexion, neutral (resting) and maximum extension. All views allowed roentgenometric evaluation of ligament instability of the lower cervical spine C5-C7 according to the White and Panjabi criteria. Furthermore, based on literature analysis and their own clinical observations, the authors proposed new classification of dynamic formation of cervical spine column. The dynamic formation of cervical column is evaluated based on pathomechanical chain of being between normal and unstable. Authors' own evaluation system in flexion views can be useful in diagnosis and treatment of this type of injury. PMID- 22098401 TI - Complementary therapies in rehabilitation: stroke patients' narratives. Part 2. AB - AIMS AND OBJECTIVES: To document the narratives of nursing staff and patients in a Thailand Rehabilitation Centre where complementary therapies are used and to discuss perceived progress of these stroke patients. Specific complementary therapies used at this Rehabilitation Centre include Thai massage and herbal therapies. BACKGROUND: Whilst there has been a small amount of quantitative research on stroke patients and complementary therapies there has been no qualitative research on the experience of stroke patients and the use of complementary therapies. DESIGN: Qualitative pilot study using narrative inquiry and discourse analysis framed by poststructural theory. METHOD: Six stroke patients were interviewed about their involvement in complementary therapy practice and treatments and their experiences of these therapies in rehabilitation. RESULTS: This study represents a reflective mining of patients' stories and captures the main theme of changes in stroke patients' embodiment and a main discourse of attending to and enabling progress. Throughout the storylines there are many other discourses such as hope, desire, helplessness, despair, fear, motivation, gratefulness, gladness and fragility. CONCLUSION: Threaded throughout the stroke patients' stories of their rehabilitation there is a layering of discourses involving tensions and a longing to overcome their disability. There are twists and detours in their stories that show the complexity of the illness experience. Progress is not straightforward with a quick recovery. Many contexts or variables influence progress such as spatiality, temporality and people. RELEVANCE TO CLINICAL PRACTICE: What is offered here is the reality of the rehabilitation process for stroke patients. Through the use of narrative inquiry the contexts of people, spatiality (environment) and temporality (time) are an important part of rehabilitation process. PMID- 22098403 TI - The absolute monocyte count is associated with overall survival in patients newly diagnosed with follicular lymphoma. AB - Follicular lymphoma is characterized by a highly variable clinical course ranging from early transformation and disease-related mortality to prolonged periods of disease stability or even spontaneous remissions. This clinical heterogeneity is likely explained by differences in the tumor microenvironment, including variable infiltration by monocyte-derived cells. Therefore, we examined the absolute monocyte count obtained from a standard complete blood count with differential at the time of diagnosis as a prognostic factor in a cohort of patients with follicular lymphoma (n = 355) treated at a single institution between 1998 and 2007. We found that the absolute monocyte count at diagnosis is associated with overall survival, independent of the Follicular Lymphoma International Prognostic Index (FLIPI). Furthermore, the absolute monocyte count improved the ability to identify high-risk patients when used in conjunction with the FLIPI. These results further support the central role of non-neoplastic myeloid-lineage cells in follicular lymphoma biology. PMID- 22098404 TI - Very poor outcome of leukemic transformation in myelofibrosis: a single center experience with 13 patients. PMID- 22098405 TI - Valproic acid combined with cytosine arabinoside in elderly patients with acute myeloid leukemia has in vitro but limited clinical activity. AB - Elderly patients with acute myeloid leukemia (AML) have a poor prognosis. The authors examined the in vitro and clinical activity of the histone deacetylase inhibitor valproic acid (VA) combined with cytosine arabinoside (AraC) in elderly patients with AML unsuited to intensive therapy. For the in vitro studies, primary AML cells from 11 patients were treated with AraC and VA and analyzed for apoptosis, cytostatic effects, differentiation and acetyl histone H3 induction. VA (alone and with AraC) enhanced apoptosis and induced acetyl histone H3. VA inhibited cell proliferation. For the clinical trial, 15 patients were treated with VA and subcutaneous AraC and assessed for toxicity and response. No complete or partial remissions were achieved. In conclusion, VA has in vitro activity against AML and has additional activity with AraC. However, in this study, this combination demonstrated limited clinical activity in elderly patients with AML. PMID- 22098406 TI - High rates of surveillance imaging for treated diffuse large B-cell lymphoma: findings from a large national database. AB - We aimed to characterize surveillance imaging and circumstances of relapse for patients with diffuse large B-cell lymphoma (DLBCL) in the National Comprehensive Cancer Network Non-Hodgkin's Lymphoma Outcomes Database, a prospective cohort study collecting clinical and outcome data at seven comprehensive cancer centers. Patients presenting with newly diagnosed DLBCL in remission >=3 months after initial therapy and who had accrued 2 years of follow-up were eligible for analysis (n = 625). The median number of imaging studies was 2.5/year (institutional range 0.5-3.5, p < 0.0001); 48.4% received only dedicated computed tomography (CT) scans, 14.6% received only positron emission tomography (PET) inclusive modalities, 32.8% received a combination and 4.2% received no imaging. Among all eligible patients, 50 (8.0%) experienced relapse, and approximately one quarter of subclinical relapses were detected through routine imaging. Our results suggest that despite limited data regarding its effect on outcomes, surveillance imaging is prevalent in DLBCL, and a majority of patients receive PET scans at some point during follow-up. PMID- 22098409 TI - New relationships connecting the dipole polarizability, radius, and second ionization potential for atoms. AB - The atomic dipole polarizability alpha of the 101 elements from He to No is related to the second ionization potential I2 and the Waber-Cromer radius r(WC). Our recommended model is the function alpha = P1.I2-4 + P2.r(WC)(3) I2(y). With the parameters P1 = 2.26, P2 = 3.912, and y = 0.439, it reproduces the polarizabilities of all 101 elements with a mean absolute deviation of 7.5 au. PMID- 22098408 TI - Hepatic gene transfer in neonatal mice by adeno-associated virus serotype 8 vector. AB - For genetic diseases that manifest at a young age with irreversible consequences, early treatment is critical and essential. Neonatal gene therapy has the advantages of achieving therapeutic effects before disease manifestation, a low vector requirement and high vector-to-cell ratio, and a relatively immature immune system. Therapeutic effects or long-term rescue of neonatal lethality have been demonstrated in several animal models. However, vigorous cell proliferation in the newborn stage is a significant challenge for nonintegrating vectors, such as adeno-associated viral (AAV) vector. Slightly delaying the injection age, and readministration at a later time, are two of the alternative strategies to solve this problem. In this study, we demonstrated robust and efficient hepatic gene transfer by self-complementary AAV8 vector in neonatal mice. However, transduction quickly decreased over a few weeks because of vector dilution caused by fast proliferation. Delaying the injection age improved sustained expression, although it also increased neutralizing antibody (NAb) responses to AAV capsid. This approach can be used to treat genetic diseases with slow progression. For genetic diseases with early onset and severe consequences, early treatment is essential. A second injection of vector of a different serotype at a later time may overcome preexisting NAb and achieve sustained therapeutic effects. PMID- 22098410 TI - Development of a Chip/Chip/SRM platform using digital chip isoelectric focusing and LC-Chip mass spectrometry for enrichment and quantitation of low abundance protein biomarkers in human plasma. AB - Protein biomarkers are critical for diagnosis, prognosis, and treatment of disease. The transition from protein biomarker discovery to verification can be a rate limiting step in clinical development of new diagnostics. Liquid chromatography-selected reaction monitoring mass spectrometry (LC-SRM MS) is becoming an important tool for biomarker verification studies in highly complex biological samples. Analyte enrichment or sample fractionation is often necessary to reduce sample complexity and improve sensitivity of SRM for quantitation of clinically relevant biomarker candidates present at the low ng/mL range in blood. In this paper, we describe an alternative method for sample preparation for LC SRM MS, which does not rely on availability of antibodies. This new platform is based on selective enrichment of proteotypic peptides from complex biological peptide mixtures via isoelectric focusing (IEF) on a digital ProteomeChip (dPC) for SRM quantitation using a triple quadrupole (QQQ) instrument with an LC-Chip (Chip/Chip/SRM). To demonstrate the value of this approach, the optimization of the Chip/Chip/SRM platform was performed using prostate specific antigen (PSA) added to female plasma as a model system. The combination of immunodepletion of albumin and IgG with peptide fractionation on the dPC, followed by SRM analysis, resulted in a limit of quantitation of PSA added to female plasma at the level of ~1-2.5 ng/mL with a CV of ~13%. The optimized platform was applied to measure levels of PSA in plasma of a small cohort of male patients with prostate cancer (PCa) and healthy matched controls with concentrations ranging from 1.5 to 25 ng/mL. A good correlation (r(2) = 0.9459) was observed between standard clinical ELISA tests and the SRM-based assay. Our data demonstrate that the combination of IEF on the dPC and SRM (Chip/Chip/SRM) can be successfully applied for verification of low abundance protein biomarkers in complex samples. PMID- 22098411 TI - Potent hepatitis B surface antigen response to treatment of hepatitis-B-e-antigen positive chronic hepatitis B with alpha-interferon plus a nucleos(t)ide analog. AB - BACKGROUND AND AIM: Hepatitis B surface antigen (HBsAg) clearance is the closest cure outcome in hepatitis B. The goal of this study was to investigate clinical features in chronic hepatitis B patients achieving seroconversion of HBsAg after treatment with alpha-interferon (IFN-alpha) and a nucleos(t)ide analog. METHODS: This retrospective study enrolled 38 chronic hepatitis B patients treated with IFN-alpha plus a nucleos(t)ide analog who achieved HBsAg seroconversion during the period from June 2001 to May 2009. Clinical and laboratory data of the patients were collected before and after treatment every 3 months. All patients with HBsAg seroconversion in this study were followed up for at least 12 months post-treatment. RESULTS: A total of 38 out of 142 patients achieved HBsAg seroconversion after treatment with IFN-alpha and a nucleos(t)tide analog for a prolonged period of time (medium 31 months). The median time to hepatitis B e antigen seroconversion and to HBsAg seroconversion was 19.5 months (range 3-60 months) and 25.5 months (range 9-63 months), respectively. Thirty-six patients (95%) sustained HBsAg seroconversion during the post-treatment follow up. Three different HBsAg response patterns were observed with classical model accounting for 57.9% (22/38 cases), simultaneous transition mode accounting for 23.7% (9/38 cases), and HBsAg prior transition model accounting for 18.4% (7/38 cases). CONCLUSIONS: Extended treatment with IFN-alpha in combination with a nucleos(t)ide analog in patients with hepatitis-B-e-antigen-positive appears to be a promising approach for achieving a high rate of HBsAg clearance-the closest outcome to cure. PMID- 22098412 TI - Nonimage-guided fine needle aspiration biopsy of palpable axillary lymph nodes in breast cancer patients. AB - We report the utility of office-based, nonimaged guided fine needle aspiration of palpable axillary lymph nodes in breast cancer patients. We examine the sensitivity and specificity of this procedure, and examine factors associated with a positive fine needle aspiration biopsy result. Although the utility of ultrasound-guided fine needle aspiration biopsy (FNA) of axillary lymph nodes is well established, there is little data on nonimage guided office-based FNA of palpable axillary lymphadenopathy. We investigated the sensitivity and specificity of nonimage-guided FNA of axillary lymphadenopathy in patients presenting with breast cancer, and report factors associated with a positive FNA result. Retrospective study of 94 patients who underwent office-based FNA of palpable axillary lymph nodes between 2004 and 2008 was conducted. Cytology results were compared with pathology after axillary sentinel node or lymph node dissection. Nonimage-guided axillary FNA was 86% sensitive and 100% specific. On univariate analysis, patients with positive FNA cytology had larger breast tumors (p = 0.007), more pathologic positive lymph nodes (p < 0.0001), and were more likely to present with a palpable breast mass (p = 0.006) or with radiographic lymphadenopathy (p = 0.002). FNA-positive patients had an increased presence of lymphovascular invasion (p = 0.001), higher stage of disease (p < 0.001), higher N stage (p < 0.0001), and higher rate of HER2/neu expression (p = 0.008). On multivariate analysis, radiographic lymphadenopathy (p = 0.03) and number of positive lymph nodes (p = 0.04) were associated with a positive FNA result. Nonimage-guided FNA of palpable axillary lymphadenopathy in breast cancer patients is an inexpensive, sensitive, and specific test. Prompt determination of lymph node positivity benefits select patients, permitting avoidance of axillary ultrasound, sentinel lymph node biopsy, or delay in receiving neoadjuvant therapy. This results in time and cost savings for the health care system, and expedites definitive management. PMID- 22098413 TI - Main and interactive effects of social support in predicting mental health symptoms in men and women following military stressor exposure. AB - Evidence across a multitude of contexts indicates that social support is associated with reduced risk for mental health symptoms. More information is needed on the effectiveness of different sources of support, as well as sex differences in support. Associations between social support from two sources - the military unit and friends and family - and mental health symptoms were examined in a study of 1571 Marine recruits assessed at the beginning and end of a highly stressful 13-week training program. Military social support buffered the stressor exposure-posttraumatic stress symptomatology (PTSS) relationship, whereas the relationship between stressor exposure and PTSS was highest when civilian social support was high. Further inspection of the interactions revealed that military support was most important at high levels of stressor exposure. Sex differences in the relationship between social support and symptoms were found, such that support from military peers was associated with lower levels of PTSS for men, whereas civilian support was associated with lower PTSS for women. While civilian social support was associated with lower levels of depression symptom severity in both women and men, the relationship was stronger for women. Reviewed implications focus on the importance of considering the recipient, source, and context of social support. PMID- 22098415 TI - EPOTRAN: a full-differential Monte Carlo code for electron and positron transport in liquid and gaseous water. AB - PURPOSE: We describe here a novel full-differential Monte Carlo (MC) event-by event simulation, for modelling electron and positron histories in liquid and gaseous water, with impact energies ranging from the water excitation threshold (7.4 eV) to 10 keV. This new track-structure code is named EPOTRAN, an acronym for Electron and POsitron TRANsport in water. MATERIAL AND METHODS: All the processes induced by both electrons and positrons are studied in detail via theoretical differential and total cross sections, calculated within the quantum mechanical framework by using the partial-wave method. Elastic and inelastic interactions are then successively reviewed, including in particular an original description of the positron-induced capture process leading to Positronium formation. RESULTS: Total and differential cross sections are reported and compared with a large set of existing measurements. Rather good agreement is generally observed over the considered energy range. CONCLUSIONS: This work reports the theoretical cross sections used in a special purpose Monte Carlo simulation suitable for electron and positron transport in gaseous and liquid water. This MC code should represent an accurate tool for dose calculation at the nanometric scale, by providing a detailed spatial distribution of energy deposits. Furthermore, positron trajectory studies made possible by this approach should prove useful for evaluating the real contribution of the positron range on the overall spatial resolution of PET (Positron Emission Tomography) imaging. PMID- 22098416 TI - IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population. AB - BACKGROUND: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. AIMS: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. METHODS: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. RESULTS: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 * 10(-5) ). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/relapse (NR/R) (P = 8.00 * 10(-3) ). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 * 10(-3) ), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 * 10(-3) and P = 2.16 * 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 * 10(-3) ); Amerindian and European ancestry genetic contribution were greater in the SVR group. CONCLUSION: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy. PMID- 22098417 TI - Role of the spleen in Bartonella spp. infection. AB - Bartonella spp. are intra-erythrocytic pathogens of mammals. In this study, we investigated the role of the spleen, and other tissue and organs in Bartonella infection. Using an in vivo model of mice infection by Bartonella birtlesii, we detected accumulation of bacteria in the spleen, with transient infection of the liver, but failed to detect any bacteria in brain or lymph nodes. We then compared bacteraemia in normal Balb/C mice and in splenectomized mice. Bacteraemia in splenectomized mice was 10-fold higher than in normal mice and lasted 2 weeks longer. In conclusion, the spleen seems to retain and filter infected erythrocytes rather than to be a sanctuary for chronic Bartonella infection. PMID- 22098418 TI - Patient-physician role relationships and patient activation among individuals with chronic illness. AB - OBJECTIVE: To examine whether chronically ill patients' perceptions of their role relationships with their physicians are associated with levels of patient activation. DATA SOURCES: Random digit dial survey of 8,140 chronically ill patients and the Area Resource File. STUDY DESIGN: Cross-sectional, multivariate analysis of the relationship between dimensions of patient-physician role relationships and level of patient activation. The study controlled for variables related to patient demographics, socioeconomic status, health status, and market and family context. PRINCIPAL FINDINGS: Higher perceived quality of interpersonal exchange with physicians, greater fairness in the treatment process, and more out of-office contact with physicians were associated with higher levels of patient activation. Treatment goal setting was not significantly associated with patient activation. CONCLUSION: Patient-physician relationships are an important factor in patients taking a more active role in their health and health care. Efforts to increase activation that focus only on individual patients ignore the important fact that the nature of roles and relationships between provider and patient can shape the behaviors and attitudes of patients in ways that support or discourage patient activation. PMID- 22098419 TI - Antioxidant and anti-inflammatory potential of hesperetin metabolites obtained from hesperetin-administered rat serum: an ex vivo approach. AB - In recent years much attention has been focused on the pharmaceutical relevance of bioflavonoids, especially hesperidin and its aglycon hesperetin in terms of their antioxidant and anti-inflammatory actions. However, the bioactivity of their metabolites, the real molecules in vivo hesperetin glucuronides/sulfates produced after ingestion, has been poorly understood. Thus, the study using an ex vivo approach is aimed to compare the antioxidant and anti-inflammatory activities of hesperidin/hesperetin or hesperetin metabolites derived from hesperetin-administered rat serum. We found that hesperetin metabolites (2.5-20 MUM) showed higher antioxidant activity against various oxidative systems, including superoxide anion scavenging, reducing power, and metal chelating effects, than that of hesperidin or hesperetin. The data also showed that pretreatment of hesperetin metabolites (1-10 MUM) within the range of physiological concentrations, compared to hesperetin, significantly inhibited nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production, as evidenced by the inhibition of their precursors, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels without appreciable cytotoxicity on LPS activated RAW264.7 macrophages or A7r5 smooth muscle cells. Concomitantly, hesperetin metabolites dose-dependently inhibited LPS-induced intracellular reactive oxygen species (ROS). Furthermore, hesperetin metabolites significantly downregulate LPS-induced nuclear factor-kappaB (NF-kappaB) activation followed by the suppression of inhibitor-kappaB (I-kappaB) degradation and phosphorylation of c-Jun N-terminal kinase1/2 (JNK1/2) and p38 MAPKs after challenge with LPS. Hesperetin metabolites ex vivo showed potent antioxidant and anti-inflammatory activity in comparison with hesperidin/hesperetin. PMID- 22098420 TI - Construction of Escherichia coli-Arthrobacter-Rhodococcus shuttle vectors based on a cryptic plasmid from Arthrobacter rhombi and investigation of their application for functional screening. AB - A cryptic plasmid from Arthrobacter rhombi PRH1, designated as pPRH, was sequenced and characterized. It was 5000 bp in length with a G+C content of 66 mol%. The plasmid pPRH was predicted to encode six putative open reading frames (ORFs), in which ORF2 and ORF3 formed the minimal replicon of plasmid pPRH and shared 55-61% and 60-69% homology, respectively, with the RepA and RepB proteins of reported rhodococcal plasmids. Sequence analysis revealed a typical ColE2-type ori located 45 bp upstream of the gene repA. Sequence and phylogenetic analysis led to the conclusion that pPRH is a representative of a novel group of pAL5000 subfamily of ColE2 family plasmids. Three shuttle vectors pRMU824, pRMU824Km and pRMU824Tc, encoding chloramphenicol resistance, were constructed. The latter two harboured additional antibiotic resistance genes kan and tet, respectively. All vectors successfully replicated in Escherichia coli, Arthrobacter and Rhodococcus spp. The vector pRMU824Km was employed for functional screening of 2 hydroxypyridine catabolism encoding genes from Arthrobacter sp. PY22. Sequence analysis of the cloned 6-kb DNA fragment revealed eight putative ORFs, among which hpyB gene encoded a putative monooxygenase. PMID- 22098421 TI - Quantifying the spatial dependence of Culicoides midge samples collected by Onderstepoort-type blacklight traps: an experimental approach to infer the range of attraction of light traps. AB - The emergence of bluetongue disease in Europe has led several countries to rapidly establish large-scale entomological surveys of its vectors, which are midges belonging to the genus Culicoides Latreille, 1809 (Diptera: Ceratopogonidae). These surveys have largely been based on the use of Onderstepoort-type blacklight traps. However, the range of attraction of the traps and the spatial dependence of the samples they provide are unknown, which somewhat complicates subsequent analyses. This paper investigates spatial interaction between Onderstepoort-type blacklight traps based on catches at a central trap placed close to two traps set in consecutive on/off modes. The spatial interaction is inferred from the drop in the number of midges collected in the central trap when nearby traps positioned at 50 m, 100 m or 200 m are turned on. The results showed a significant spatial interaction between traps separated by 50 m for female Culicoides obsoletus/Culicoides scoticus and Culicoides dewulfi. No significant interaction was found for female Culicoides of other species, for male Culicoides, or for traps spaced at >=100 m. Based on the experimental design geometry and on simple assumptions on the distribution of Culicoides midges in the neighbourhood of the traps, the paper also presents a method to infer the range of attraction of the traps. PMID- 22098423 TI - Home hemodialysis in the remote Canadian north: treatment in Manitoba fly-in communities. AB - Manitoba has the highest prevalence of ESRD in Canada. Northern Manitoba is a very sparsely settled area with a high proportion of aboriginal ESRD patients. Relocating to urban areas for dialysis is psychosocially and culturally stressful to patients. Delivering dialysis care in a home setting has demonstrated advantages in both clinical, economic, and health related quality of life domains. Establishing home hemodialysis in very remote communities has significant challenges, including poor and inadequate housing, unreliable water supply, limited community medical backup, and poor road access to communities especially for delivery of supplies. These challenges necessitate the development of strong community partnerships, and well documented processes for contingencies. A dedicated interdisciplinary support and training team at the urban hub is essential. PMID- 22098424 TI - Room-temperature tunnel magnetoresistance in self-assembled chemically synthesized metallic iron nanoparticles. AB - We report on room temperature magnetoresistance in networks of chemically synthesized metallic Fe nanoparticles surrounded by two types of organic barriers. Electrical properties, featuring Coulomb blockade, and magnetotransport measurements show that this magnetoresistance arises from spin-dependent tunnelling, so the organic ligands stabilizing the nanoparticles are efficient spin-conservative tunnel barrier. These results demonstrate the feasibility of an all-chemistry approach for room temperature spintronics. PMID- 22098422 TI - Altered apoptotic responses in neurons lacking RhoB GTPase. AB - Caspase 3 activation has been linked to the acute neurotoxic effects of central nervous system damage, as in traumatic brain injury or cerebral ischaemia, and also to the early events leading to long-term neurodegeneration, as in Alzheimer's disease. However, the precise mechanisms activating caspase 3 in neuronal injury are unclear. RhoB is a member of the Rho GTPase family that is dramatically induced by cerebral ischaemia or neurotrauma, both in preclinical models and clinically. In the current study, we tested the hypothesis that RhoB might directly modulate caspase 3 activity and apoptotic or necrotic responses in neurons. Over-expression of RhoB in the NG108-15 neuronal cell line or in cultured corticohippocampal neurons elevated caspase 3 activity without inducing overt toxicity. Cultured corticohippocampal neurons from RhoB knockout mice did not show any differences in sensitivity to a necrotic stimulus - acute calcium ionophore exposure - compared with neurons from wild-type mice. However, corticohippocampal neurons lacking RhoB exhibited a reduction in the degree of DNA fragmentation and caspase 3 activation induced by the apoptotic agent staurosporine, in parallel with increased neuronal survival. Staurosporine induction of caspase 9 activity was also suppressed. RhoB knockout mice showed reduced basal levels of caspase 3 activity in the adult brain. These data directly implicate neuronal RhoB in caspase 3 activation and the initial stages of programmed cell death, and suggest that RhoB may represent an attractive target for therapeutic intervention in conditions involving elevated caspase 3 activity in the central nervous system. PMID- 22098425 TI - Obesity and melanoma. PMID- 22098426 TI - Tuning of the critical temperature in iron(II) spin-crossover materials based on bridging polycyanidometallates: pentacyanidonitrosylferrate(II) and hexacyanidoplatinate(IV). AB - The reactions of iron(II) sulfate, 4-amino-3,5-di-2-pyridyl-4H-1,2,4-triazole (abpt), and pentacyanidonitrosylferrate(II) or hexacyanidoplatinate(IV) resulted in the formation of one-dimensional iron(II) spin-crossover compounds [Fe(abpt)(2)(MU-Fe(CN)(5)(NO))](n) (1) and [Fe(abpt)(2)(MU-Pt(CN)(6))](n) (2) with the spin-transition critical temperature near or above room temperature accompanied by thermochromism. Furthermore, it has been proven that the critical temperature T(c) is influenced by the type of dianionic polycyanidometallate within the series of discussed systems, and it changes in the sequence of [Fe(CN)(5)(NO)](2-) < [Pt(CN)(6))](2-) < [Ni(CN)(4))](2-) ~ [Pd(CN)(4))](2-) ~ [Pt(CN)(4))](2-). PMID- 22098427 TI - High-throughput multiplex PCR genotyping for 35 red blood cell antigens in blood donors. AB - BACKGROUND AND OBJECTIVES: One to two per cent of patients in need of red cell transfusion carry irregular antibodies to red blood cell (RBC) antigens and have to be supplied with specially selected blood units. To be able to respond to those requests, blood centres have to screen a significant number of donors for a variety of antigens serologically, which is a costly and through the shortage of reagents, also limited procedure. To make this procedure more efficient, the Austrian Red Cross has developed a genotyping assay as an alternative approach for high throughput RBC typing. MATERIALS AND METHODS: A multiplex polymerase chain reaction (PCR) assay was designed for typing 35 RBC antigens in six reaction mixes. The assay includes both common as well as high-frequency-alleles: MNS1, MNS2, MNS3 and MNS4; LU1, LU2, LU8 and LU14; KEL1, KEL2, KEL3, KEL4, KEL6, KEL7, KEL11, KEL17 and KEL21; FY1, FY2, FYB(WK) and FY0 (FYB(ES)); JK1 and JK2; DI1, DI2, DI3 and DI4; YT1 and YT2; DO1 and DO2; CO1 and CO2; IN1 and IN2. The assay was validated using 370 selected serologically typed samples. Subsequently 6000 individuals were screened to identify high frequency antigen (HFA)-negative donors and to facilitate the search for compatible blood for alloimmunized patients. RESULTS: All controls showed complete concordance for the tested markers. The screening of 6000 donors revealed 57 new HFA-negative donors and the blood group database was extended by approximately 210,000 results. CONCLUSION: The study shows that in practice, this high-throughput genotyping assay is feasible, fast and provides reliable results. Compared to serological testing, this molecular approach is also very cost-efficient. PMID- 22098428 TI - Left ventricular systolic dyssynchrony index by three-dimensional echocardiography in patients with decreased left ventricular function: comparison with tissue Doppler echocardiography. AB - BACKGROUND: Three-dimensional echocardiography (3DE) can simultaneously assess left ventricular (LV) regional systolic motion and global LV mechanical dyssynchrony. METHODS: We used 3DE to measure systolic dyssynchrony index (SDI) (standard deviation of the time from cardiac cycle onset to minimum systolic volume in 17 LV segments) in 100 patients and analyzed the association of SDI with other parameters for LV systolic function or dyssynchrony. Eighteen patients who underwent cardiac resynchronization therapy (CRT) were also evaluated at 6 months after CRT, and the association of baseline SDI and tissue Doppler imaging (TDI) dyssynchrony index (Ts-SD) with the change of LV end-systolic volume (ESV) analyzed. Ts-SD was calculated using the standard deviation of the time from the QRS complex to peak systolic velocity. RESULTS: There was a significant inverse correlation between LVEF and SDI (r =-0.686, P < 0.0001). QRS duration was also significantly correlated to SDI (r = 0.407, P < 0.0001). There was a significant positive correlation between baseline SDI and the decrease in LVESV after CRT (r = 0.42). Baseline SDI was significantly greater in responders (10 patients) than in nonresponders (16.4 +/- 5.1 vs. 7.9 +/- 2.4%, P < 0.01), but there was no significant difference in Ts-SD. SDI > 11.9% predicted CRT response with a sensitivity of 90% and a specificity of 75%. CONCLUSIONS: SDI derived from 3DE is a useful parameter to assess global LV systolic dyssynchrony and predict responses to CRT. PMID- 22098429 TI - Stilbene-chalcone hybrids: design, synthesis, and evaluation as a new class of antimalarial scaffolds that trigger cell death through stage specific apoptosis. AB - Novel stilbene-chalcone (S-C) hybrids were synthesized via a sequential Claisen Schmidt-Knoevenagel-Heck approach and evaluated for antiplasmodial activity in in vitro red cell culture using SYBR Green I assay. The most potent hybrid (11) showed IC(50) of 2.2, 1.4, and 6.4 MUM against 3D7 (chloroquine sensitive), Indo, and Dd2 (chloroquine resistant) strains of Plasmodium falciparum, respectively. Interestingly, the respective individual stilbene (IC(50) > 100 MUM), chalcone (IC(50) = 11.5 MUM), or an equimolar mixture of stilbene and chalcone (IC(50) = 32.5 MUM) were less potent than 11. Studies done using specific stage enriched cultures and parasite in continuous culture indicate that 11 and 18 spare the schizont but block the progression of the parasite life cycle at the ring or the trophozoite stages. Further, 11 and 18 caused chromatin condensation, DNA fragmentation, and loss of mitochondrial membrane potential in Plasmodium falciparum, thereby suggesting their ability to cause apoptosis in malaria parasite. PMID- 22098430 TI - Carbon fiber-reinforced cyanate ester/nano-ZrW2O8 composites with tailored thermal expansion. AB - Fiber-reinforced composites are widely used in the design and fabrication of a variety of high performance aerospace components. The mismatch in coefficient of thermal expansion (CTE) between the high CTE polymer matrix and low CTE fiber reinforcements in such composite systems can lead to dimensional instability and deterioration of material lifetimes due to development of residual thermal stresses. The magnitude of thermally induced residual stresses in fiber reinforced composite systems can be minimized by replacement of conventional polymer matrices with a low CTE, polymer nanocomposite matrix. Zirconium tungstate (ZrW(2)O(8)) is a unique ceramic material that exhibits isotropic negative thermal expansion and has excellent potential as a filler for development of low CTE polymer nanocomposites. In this paper, we report the fabrication and thermal characterization of novel, multiscale, macro-nano hybrid composite laminates comprising bisphenol E cyanate ester (BECy)/ZrW(2)O(8) nanocomposite matrices reinforced with unidirectional carbon fibers. The results reveal that incorporation of nanoparticles facilitates a reduction in CTE of the composite systems, which in turn results in a reduction in panel warpage and curvature after the cure because of mitigation of thermally induced residual stresses. PMID- 22098431 TI - Relevance of the inner mitochondrial membrane enzyme F1F0-ATPase as an autoantigen in autoimmune liver disorders. AB - BACKGROUND AND AIMS: Recently, a non-M2-related mitochondrial 60 kDa protein found to be recognized by antimitochondrial antibody (AMA) negative sera from patients with primary biliary cirrhosis (PBC) has been shown to contain parts of the five F(1)-ATPase subunits alpha, beta, gamma, delta and epsilon. In this study, we examined whether this enzyme is, indeed, a target antigen in PBC. METHODS: Analysed were 60 AMA-positive/anti-M2-negative and 103 anti-M2-positive PBC patients, 46 patients with autoimmune hepatitis (AIH), 35 patients with primary sclerosing cholangitis (PSC), 110 patients with viral hepatitis, 40 patients with inflammatory bowel diseases (IBD), 33 patients with connective tissue diseases (systemic lupus erythematosus, mixed connective tissue disease, Sjogren disease, systemic sclerosis) and 25 blood donors. The F(1)-ATPase subunits alpha-delta were recombinantly expressed in Escherichia coli, purified and applied to ELISA and Western blotting. RESULTS: In all, 40 of the 60 AMA positive/anti-M2-negative (67%) and 44 (43%) of the 103 anti-M2-positive PBC-sera reacted with at least one of the F(1)-subunits alpha-delta. The beta- and gamma subunits were preferentially recognized. However, also up to 57% of patients with AIH and 34% of patients with PSC had anti-beta- or gamma-antibodies, while patients with viral hepatitis had these antibodies in up to 13%. Patients with IBD had anti-beta and anti-gamma-antibodies in up to 20 and 5% respectively. None of the patients with connective tissue diseases had antibodies to the beta- and only 6% to the gamma-subunit. Sera from healthy blood donors were negative. CONCLUSIONS: Antibodies to the beta- and gamma-subunits of F(1)-ATPase are further AMAs in PBC but occur also in other autoimmune liver disorders; they may be, therefore, indicators for a general autoimmune process of the liver. PMID- 22098433 TI - Clinical comparison of new monoclonal antibody-based nephelometric assays for free light chain kappa and lambda to polyclonal antibody-based assays and immunofixation electrophoresis. AB - BACKGROUND: New monoclonal antibody-based assays for serum-free light chains (FLC) have become available. METHODS: In a clinical study with 541 patients, the new N Latex FLC assays were compared with the Freelite FLC assays and immunofixation electrophoresis (IF). RESULTS: Comparison of the different FLC kappa (kappa) assays showed a slope of 0.99 with a deviation of 5.0%, rs=0.92, for FLC lambda (lambda) a slope of 1.22, deviation 13.8%, rs=0.90 and for the kappa/lambda ratio a slope of 0.72, deviation -4.6%, rs=0.72. The concordance for the FLC kappa assays was 91%, for FLC lambda 85% and kappa/lambda ratio 95%. The clinical sensitivity and specificity of the kappa/lambda ratios in the study were comparable: 60% and 99% for the N Latex FLC assay and 61% and 97% for the Freelite assay. In IF-FLC positive samples, the N Latex FLC kappa/lambda ratio scored 20/23 (87%) samples outside the reference range and Freelite 21/23 (91%). For IF-FLC negative samples, N Latex FLC assay kappa/lambda ratio scored 338/350 (97%) within the reference range and Freelite scored 332/350 (95%). CONCLUSIONS: The concordance scores and the clinical sensitivity and specificity of the new N Latex FLC assays and Freelite assays appeared comparable, but there are some differences in measurement of concentrations between the methods. PMID- 22098435 TI - Urinary 8-hydroxy-2'-deoxyguanosine level and plasma paraoxonase 1 activity with Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease (AD) is the most frequent cause of dementia and age is the most important risk factor for AD. Aging is associated with increased free radical production and oxidative stress plays an important role in the pathogenesis of AD. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a biomarker indicating oxidative DNA damage. Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme and prevents especially oxidation of low-density lipoproteins. The aim of this study is to measure urinary 8-OHdG levels and serum PON1 activity in patients with AD. METHODS: A total of 21 elderly patients diagnosed with moderate AD (10 men and 11 women, aged 76 +/- 7.8 years) were included in the study. A total of 20 healthy elderly volunteers (11 men and nine women, aged 81 +/- 7.2 years) were enrolled as a control group. Levels of urinary 8-OHdG, serum PON1 activity and lipid profile were determined in patients and controls. RESULTS: Urinary 8-OHdG levels were significantly increased, but serum PON1 activity was significantly decreased in patients compared to controls. Lipid profile did not show a difference between the groups. There was a negative correlation between 8-OHdG levels and PON1 activity only in the patient group (r=-0.536). Analytical performance characteristics of the methods used were satisfactory. CONCLUSIONS: In this study, evidence of increased oxidative DNA damage was determined in AD patients as well as decreased serum PON1 activity. Oxidant stress and oxidative DNA damage are important pathological processes in AD. The biomarkers, urinary 8-OHdG level and serum PON1 activity can be used to determine and monitor the status of patients with AD. PMID- 22098436 TI - Minimum analytical quality specifications of inter-laboratory comparisons: agreement among Spanish EQAP organizers. AB - BACKGROUND: Four Spanish scientific societies organizing external quality assessment programs (EQAP) formed a working group to promote the use of common minimum quality specifications for clinical tests. Laboratories that do not meet the minimum specifications are encouraged to make immediate review of the analytical procedure affected and to implement corrective actions if necessary. METHODS: The philosophy was to use the 95th percentile of results sent to EQAP (expressed in terms of percentage deviation from the target value) obtained for all results (except the outliers) during a cycle of 1 year. The target value for a number of analytes of the basic biochemistry program was established as the overall mean. However, because of the substantial discrepancies between routine methods for basic hematology, hormones, proteins, therapeutic drugs and tumor markers, the target in these cases was the peer group mean. RESULTS: The resulting specifications were quite similar to those established in the US (CLIA), and Germany (Richtlinie). CONCLUSIONS: The proposed specifications stand for the minimum level of quality to be attained for laboratories, to assure harmonized service performance. They have nothing to do with satisfying clinical requirements, which are the final level of quality to be reached, and that is strongly recommended in our organizations by means of documents, courses, symposiums and all types of educational activities. PMID- 22098438 TI - The relationship between antinuclear antibody data and antibodies against extractable nuclear antigens in a large laboratory cohort. AB - BACKGROUND: Anti-extractable nuclear antigen antibodies (anti-ENA) have diagnostic significance in systemic rheumatic disease (SRD). METHODS: Anti-ENA were tested in 1685/30,196 sera that were submitted sequentially for antinuclear antibody (ANA) testing. Frequency was stratified by ANA titer and pattern, by referral source, by submitted diagnosis and by patient age and sex. RESULTS: Anti ENA frequency increased with ANA titer (7.3% at < 32%-43.3% at >= 1024). Anti histone (11.6%) and anti-SSA/SSB (13.9%) were the most frequent finding with a homo?xadgeneous pattern; anti-SSA/SSB (39.7%) and anti-RNP/anti-Sm (37.7%) were the most frequent finding with a speckled pattern. Sera with speckled, multiple and homogenous ANA patterns accounted for 92.6% of positive anti-ENA findings. At ANA titer >= 256, 29.2% of these sera were tested for anti-ENA, of which 41.2% were positive; frequency was higher with an accompanying diagnosis of SRD (53.5% vs. 36.5%, p < 0.004 by chi2-test) but not with referral by rheumatologists (43.5% vs. 35.9%) and did not differ by patient age or sex. CONCLUSIONS: Reflexive anti-ENA testing may be helpful among sera with ANA titer >= 256 and homogeneous, speckled or multiple patterns, irrespective of referral source or accompanying diagnosis. Further work is needed to evaluate the clinical impact of this protocol. PMID- 22098440 TI - A pilot study of the novel offset-tip papillotome for selective biliary cannulation in ERCP. AB - INTRODUCTION: We developed a new offset-tip papillotome to facilitate biliary cannulation and reduce the incidence of unintended contrast injection into the pancreatic duct during ERCP. The aim of the present retrospective cohort study was to evaluate the utility of the novel offset-tip papillotome in achievement of biliary cannulation, and prevention of unintended contrast injection into the pancreatic duct during ERCP, compared with a standard straight-tip catheter. MATERIAL AND METHODS: Patients with native papilla who required biliary ERCP were retrospectively reviewed. Biliary ERCPs were performed by two experienced endoscopists using either the offset-tip papillotome or a standard catheter. Patients in whom ERCP involved fellows in training were excluded. RESULTS: Eighty five patients were included and divided into two cohorts: The offset-tip papillotome (OT; n = 40) and the standard straight-tip cohort (ST; n = 45). Biliary cannulation success rates in OT and ST cohort were 92.5% and 88.9%, respectively. The frequency of unintended contrast injection into the pancreatic duct and time to biliary cannulation of the OT cohort during biliary cannulation were significantly less than those of the ST cohort (0.56 vs. 1.65 times and 103.3 vs. 287.9 seconds). CONCLUSION: The novel offset-tip papillotome could reduce the incidence of unintended contrast injection into the pancreatic duct and the time to biliary cannulation. PMID- 22098441 TI - Laparoscopic approaches for splenic artery aneurysms. AB - BACKGROUND: Therapeutic options for splenic artery aneurysm include endovascular management, laparoscopic surgery, and open surgery, although their indications and applications as standard therapy remain controversial. METHODS: Between August 2009 and March 2011, three patients with splenic artery aneurysm were treated at our institution. All patients underwent laparoscopic surgery. RESULTS: There was no conversion to open surgery. The mean operative time was 204.7 min (range: 147-265 min) and the mean intraoperative blood loss was 30 mL (range: 0 90 mL). There was no mortality or morbidity. CONCLUSIONS: The laparoscopic approaches for splenic artery aneurysm were safe procedures. PMID- 22098442 TI - The fibres and polyphenols in sea buckthorn (Hippophae rhamnoides) extraction residues delay postprandial lipemia. AB - The triacylglycerol (TAG) response to fatty meals containing dried and crushed berries or berry extraction residues was studied in a postprandial cross-over study with healthy normal-weight male volunteers. The berry material included sea buckthorn berries, sea buckthorn CO2 extraction residue (CO2-sea buckthorn) and sea buckthorn or black currant CO2 and ethanol extraction residue (CO2-EtOH-sea buckthorn, CO2-EtOH-black currant). Extraction residues were used in order to advance the potential use of valuable side stream components containing polyphenols and fibre as human food. Compared to the berry-depleted control, all berry meals delayed lipemia, whereas there were no differences in the total area under the TAG response curve. The lipemic delay largely derived from the fibre rather than from the polyphenols. Even so, the effect of polyphenols may be complementary since sea buckthorn and CO2-sea buckthorn showed significant differences in relation to control in a wider range of TAG areas than polyphenol depleted CO2-EtOH-sea buckthorn. PMID- 22098443 TI - Liver protein profiling in chronic hepatitis C: identification of potential predictive markers for interferon therapy outcome. AB - The current anti-hepatitis C virus (HCV) therapy, based on pegylated-interferon alpha and ribavirin, has limited success rate and is accompanied by several side effects. The aim of this study was to identify protein profiles in pretreatment liver biopsies of HCV patients correlating with the outcome of antiviral therapy. Cytosolic or membrane/organelle-enriched protein extracts from liver biopsies of eight HCV patients were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Overall, this analysis identified 21 proteins whose expression levels correlate with therapy response. These factors are involved in interferon-mediated antiviral activity, stress response, and energy metabolism. Moreover, we found that post-translational modifications of dihydroxyacetone kinase were also associated with therapy outcome. Differential expression of the five best performing markers (STAT1, Mx1, DD4, DAK, and PD ECGF) was confirmed by immunoblotting assays in an independent group of HCV patients. Finally, we showed that a prediction model based on the expression levels of these markers classifies responder and nonresponder patients with an accuracy of 85.7%. These results provide evidence that the analysis of pretreatment liver protein profiles is valuable for discriminating between responder and nonresponder HCV patients, and may contribute to reduce the number of nonresponder patients exposed to therapy-associated risks. PMID- 22098444 TI - Effects of transglucosidase on diabetes, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled trial. AB - In this 12-week, randomized, double-blind, placebo-controlled trial, the efficacy and safety of transglucosidase (TGD) were compared with placebo in patients with type 2 diabetes mellitus (T2DM). At 12 weeks, TGD 300 mg/day and TGD 900 mg/day significantly reduced HbA1c (0.18 and 0.21%) and insulin concentration (19.4 and 25.0 pmol/l), respectively, vs. placebo. TGD 300 mg/day and TGD 900 mg/day also significantly reduced low-density lipoprotein cholesterol (0.22 and 0.17 mmol/l, respectively). TGD 900 mg/day significantly reduced triglyceride by 0.24 mmol/l and diastolic blood pressure by 8 mmHg. Placebo was associated with a significant increase from baseline in body mass index, alanine aminotransferase and aspartate aminotransferase (0.17 kg/m(2) , 3 and 2 U/l, respectively), whereas TGD was not. TGD 300 mg/day significantly increased high-molecular-weight adiponectin by 0.6 ug/ml. Adverse events did not differ significantly between the groups. TGD resulted in lowering of HbA1c and blood insulin level and improvements in metabolic and cardiovascular risk factors in T2DM. PMID- 22098445 TI - The emerging discipline of behavioral neuroimaging. PMID- 22098446 TI - Functional magnetic resonance imaging in awake animals. AB - Awake animal imaging is becoming an important tool in behavioral neuroscience and preclinical drug discovery. Non-invasive ultra-high-field, functional magnetic resonance imaging (fMRI) provides a window to the mind, making it possible to image changes in brain activity across distributed, integrated neural circuits with high temporal and spatial resolution. In theory, changes in brain function, anatomy, and chemistry can be recorded in the same animal from early life into old age under stable or changing environmental conditions. This prospective capability of animal imaging to follow changes in brain neurobiology after genetic or environmental insult has great value to the fields of psychiatry and neurology and probably stands as the key advantage of MRI over other methods in the neuroscience toolbox. In addition, awake animal imaging offers the ability to record signal changes across the entire brain in seconds. When combined with the use of 3D segmented, annotated, brain atlases, and computational analysis, it is possible to reconstruct distributed, integrated neural circuits or 'fingerprints' of brain activity. These fingerprints can be used to characterize the activity and function of new psychotherapeutics in preclinical development and to study the neurobiology of integrated neural circuits controlling cognition and emotion. In this review, we describe the methods used to image awake animals and the recent advances in the radiofrequency electronics, pulse sequences, and the development of 3D segmented atlases and software for image analysis. Results from pharmacological MRI studies and from studies using provocation paradigms to elicit emotional responses are provided as a small sample of the number of different applications possible with awake animal imaging. PMID- 22098447 TI - Motion-tracking technique in unrestrained small-animal single-photon emission computed tomography. AB - Medical researchers have used structural and functional imaging techniques to study various neurological phenomena. Humans are typically conscious for both structural and functional neuroimaging studies. The use of functional neuro imaging techniques in mouse-based animal models is typically accomplished with restrained or anesthetized mice. A system was developed to perform functional imaging with single-photon emission computed tomography of awake mice to avoid the confounding influences of anesthesia or physical restraint. This review article provides an overview of the technique and how it is presently being used. The system is designed for brain imaging and uses infrared reflectors to track the head position as a function of time. The detected photons are acquired in list mode and are time-stamped. The position of the rotating gamma camera is also recorded as a function of time. These three sets of data are integrated together in an iterative image reconstruction program that performs motion compensation. The successful performance of the system is demonstrated in moving phantom and awake animal studies. The system and methodology has the potential of being a powerful tool in behavioral neuroimaging studies involving awake, unrestrained mice. PMID- 22098448 TI - Manganese enhanced MRI (MEMRI): neurophysiological applications. AB - Manganese ion (Mn(2+)) is a calcium (Ca(2+)) analog that can enter neurons and other excitable cells through voltage gated Ca(2+) channels. Mn(2+) is also a paramagnetic that shortens the spin-lattice relaxation time constant (T(1)) of tissues where it has accumulated, resulting in positive contrast enhancement. Mn(2+) was first investigated as a magnetic resonance imaging (MRI) contrast agent approximately 20 years ago to assess the toxicity of the metal in rats. In the late 1990s, Alan Koretsky and colleagues pioneered the use of manganese enhanced MRI (MEMRI) towards studying brain activity, tract tracing and enhancing anatomical detail. This review will describe the methodologies and applications of MEMRI in the following areas: monitoring brain activity in animal models, in vivo neuronal tract tracing and using MEMRI to assess in vivo axonal transport rates. PMID- 22098449 TI - Integrating PET with behavioral neuroscience using RatCAP tomography. AB - Behavioral studies are an important part of neuroscience. They allow inferences about the functions of the brain and any internal states and processes it controls. Positron emission tomography (PET) is an in vivo imaging technique that provides insights into the mechanisms of neuronal communication. In this review, we focus on some of the contributions of PET to the field of behavioral neuroscience. Small animals typically require anesthesia to remain still during PET imaging, which places a burden on behavioral studies. Our approach integrates PET with behavioral observations using a miniature PET scanner that rats wear on the head, a mobility system to facilitate animal movement and ways to integrate the PET data with behavioral measures. We summarize our studies that assessed spontaneous, self-initiated behavioral activity and dopamine D2 receptor functions simultaneously. PMID- 22098450 TI - Fine epitope mapping within the pathogenic thyroglobulin peptide 2340-2359: minimal epitopes retaining antigenicity across various MHC haplotypes are not necessarily immunogenic. AB - We have previously reported that the 20-mer peptide p2340 (amino acids 2340 2359), of human thyroglobulin (Tg) has the unique feature that it causes experimental autoimmune thyroiditis (EAT) in mouse strains bearing high-responder (HR) or low-responder (LR) MHC haplotypes in Tg-induced EAT. In this study, we have employed fine epitope mapping to examine whether this property of p2340 is the result of recognition of distinct or shared minimal T-cell epitopes in the context of HR or LR MHC class II molecules. Use of overlapping peptides showed that a core minimal 9-mer epitope (LTWVQTHIR, amino acids 2344-2352) was recognized by p2340-primed T cells from both HR (H2(k,s) ) and LR (H2(b,d) ) strains, whereas a second 9-mer epitope (HIRGFGGDP, amino acids 2350-2358) was antigenic only in H2(s) hosts. Truncation analysis of LTWVQTHIR and HIRGFGGDP peptides delineated them as the minimal epitopes recognized by p2340-primed T cells from the above strains. Subcutaneous challenge of all mouse strains with the 9-mer core peptide LTWVQTHIR in adjuvant elicited specific lymph node cell proliferative responses and mild EAT only in HR hosts, highlighting this sequence as a minimal pathogenic Tg peptide in EAT. The 9-mer peptide HIRGFGGDP was not found to be immunogenic in H2(s) hosts. These data demonstrate that minimal T cell epitopes, defined as autoantigenic in hosts of various MHC haplotypes, are not intrinsically immunogenic. Activation of naive autoreactive T cells may require contributions from flanking residues within longer peptide sequences encompassing these epitopes. PMID- 22098452 TI - Acute-on-chronic liver failure in chronic hepatitis B. AB - Acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is most commonly caused by acute severe exacerbation of CHB. The pathophysiology of ACLF in CHB is still poorly understood. Despite the identification of important predisposing factors and prognostic markers, ACLF in CHB remains a disease associated with high mortality. The majority of studies using nucleoside analog therapy did not show any significant improvement in survival, although larger prospective studies are needed. Liver transplantation is the definitive treatment for ACLF in CHB. The challenge ahead would be prognosticating cases with favorable or unfavorable outcomes in order to streamline patients for early transplantation or for medical therapy. PMID- 22098451 TI - Risk factors for complications of radiation therapy on tissue expander breast reconstructions. AB - Radiation therapy has been shown to increase complication rates of tissue expander/implant breast reconstructions. The purpose of this study was to evaluate patient characteristics to assess their impact on complications. A retrospective review of patients who underwent mastectomy plus tissue expander/implant reconstruction from January 2000 to December 2006 was performed. The main outcome of interest was the development of postoperative complications. Analyses were performed to detect risk factors for complications. A total of 560 patients were included in the study. A total of 385 patients underwent unilateral and 174 underwent bilateral tissue expander/implant reconstructions, for a total of 733 reconstructions. A total complication rate of 31.8% and a major complication rate of 24.4% were calculated. The risk factors associated with a significantly increased incidence of complications were age greater than 50 years, body mass index (BMI) greater than 30, and radiation. Women younger than 50 years had a complication rate of 28.4%, whereas women older than 50 years had a complication rate of 37.0%. Women with a BMI less than 30 had a complication rate of 27.5%, whereas women with a BMI greater than 30 had a complication rate of 49%. The major complication rate in nonradiated and radiated patients was 21.2% and 45.4%, respectively. Despite higher complication rates, tissue expander/implant reconstructions were successful in 70.1% of radiated patients. Based on this study, the ideal radiated patient would have a BMI less than 30 and be younger than 50 years of age to maximize the likelihood of a successful tissue expander/implant reconstruction. PMID- 22098453 TI - The risk factors effecting the dry mouth in inpatients in Hospital in west Anatolia. AB - AIM: The aim of the present study was to evaluate the inpatients with dry mouth and the associated risk factors. BACKGROUND: Dry mouth is defined as the excessive decrease in the amount of saliva. Hyposalivation may lead to rapid deterioration in oral health and may facilitate the development of opportunistic oral infections. Oral hygiene and evaluation of oral health are basic nursing activities. DESIGN: Cross-sectional. PARTICIPANTS: The sample size was determined to be 90 inpatients according to the power analysis calculated for the patients with dry mouth who were able or unable to take oral liquids. The study was completed with 247 inpatients in the Internal Medicine Clinic. METHODS: A patient information form was used to collect the data for the present study. Saliva samples taken for analyses of flow rates. RESULTS: The amount of saliva of patients who were unable to take oral liquid was 10.7 times lower than those taking >1500 ml of liquids daily. The amount of saliva of patients receiving humidified oxygen was 2.3 times lower than those not receiving humidified oxygen. The amount of saliva of those receiving anticholinergic drugs was 3.64 times lower than those not receiving anticholinergic drugs. CONCLUSIONS: Inability to take oral liquids and receiving humidified oxygen and anticholinergic drug therapy were significant factors for the development of dry mouth. RELEVANCE TO CLINICAL PRACTICE: The results are important for determining the risk factors for dry mouth. Being aware of dry mouth and knowing the associated risk factors are valuable information for nurses to initiate required procedures, as well as to prevent the development of oral health problems. PMID- 22098454 TI - Imaging protein-protein interactions inside living cells via interaction dependent fluorophore ligation. AB - We report a new method, Interaction-Dependent PRobe Incorporation Mediated by Enzymes, or ID-PRIME, for imaging protein-protein interactions (PPIs) inside living cells. ID-PRIME utilizes a mutant of Escherichia coli lipoic acid ligase, LplA(W37V), which can catalyze the covalent ligation of a coumarin fluorophore onto a peptide recognition sequence called LAP1. The affinity between the ligase and LAP1 is tuned such that, when each is fused to a protein partner of interest, LplA(W37V) labels LAP1 with coumarin only when the protein partners to which they are fused bring them together. Coumarin labeling in the absence of such interaction is low or undetectable. Characterization of ID-PRIME in living mammalian cells shows that multiple protein-protein interactions can be imaged (FRB-FKBP, Fos-Jun, and neuroligin-PSD-95), with as little as 10 min of coumarin treatment. The signal intensity and detection sensitivity are similar to those of the widely used fluorescent protein complementation technique (BiFC) for PPI detection, without the disadvantage of irreversible complex trapping. ID-PRIME provides a powerful and complementary approach to existing methods for visualization of PPIs in living cells with spatial and temporal resolution. PMID- 22098456 TI - Corynebacterium glutamicum whcB, a stationary phase-specific regulatory gene. AB - The function of whcB, one of the four whiB homologues of Corynebacterium glutamicum, was assessed. Cells carrying the P(180)-whcB clone, and thus overexpressing the whcB gene, showed retarded growth, probably due to increased sensitivity to oxidants, whereas cells lacking whcB (DeltawhcB) did not. However, growth retardation was not observed in cells with additionally whcE deleted. Furthermore, the DeltawhcE phenotype, characterized by slow growth and sensitivity to oxidants, was reversed in cells carrying P(180)-whcB. Like the whcE gene, which is also known as a whiB homologue, the whcB gene was preferentially expressed in stationary phase. Determination of the genes under regulation of whcB using two-dimensional polyacrylamide gel electrophoresis identified several genes involved in electron transfer reactions that were regulated in cells carrying P(180)-whcB. Collectively, these findings indicate that whcB function requires whcE. Furthermore, whcB and whcE are paralogues but perform distinct regulatory roles during growth under oxidative stress. PMID- 22098455 TI - Artificial feeding synchronizes behavioral, hormonal, metabolic and neural parameters in mother-deprived neonatal rabbit pups. AB - Nursing in the rabbit is under circadian control, and pups have a daily anticipatory behavioral arousal synchronized to this unique event, but it is not known which signal is the main entraining cue. In the present study, we hypothesized that food is the main entraining signal. Using mother-deprived pups, we tested the effects of artificial feeding on the synchronization of locomotor behavior, plasma glucose, corticosterone, c-Fos (FOS) and PERIOD1 (PER1) rhythms in suprachiasmatic, supraoptic, paraventricular and tuberomammillary nuclei. At postnatal day 1, an intragastric tube was placed by gastrostomy. The next day and for the rest of the experiment, pups were fed with a milk formula through the cannula at either 02:00 h or 10:00 h [feeding time = zeitgeber time (ZT)0]. At postnatal days 5-7, pups exhibited behavioral arousal, with a significant increase in locomotor behavior 60 min before feeding. Glucose levels increased after feeding, peaking at ZT4-ZT12 and then declining. Corticosterone levels were highest around the time of feeding, and then decreased to trough concentrations at ZT12-ZT16, increasing again in anticipation of the next feeding bout. In the brain, the suprachiasmatic nucleus had a rhythm of FOS and PER1 that was not significantly affected by the feeding schedule. Conversely, the supraoptic, paraventricular and tuberomammillary nuclei had rhythms of both FOS and PER1 induced by the time of scheduled feeding. We conclude that the nursing rabbit pup is a natural model of food entrainment, as food, in this case milk formula, is a strong synchronizing signal for behavioral, hormonal, metabolic and neural parameters. PMID- 22098457 TI - Effect of antimicrobial residues on early adhesion and biofilm formation by wild type and benzalkonium chloride-adapted Pseudomonas aeruginosa. AB - Antimicrobial residue deposition can change the physico-chemical properties of bacteria and surfaces and thus promote or impair bacterial adhesion. This study focuses on benzalkonium chloride (BC) deposition on polystyrene (PS) surfaces and the influence of this conditioning film on the physico-chemical properties of PS and on early adhesion and biofilm formation by Pseudomonas aeruginosa wild-type and its laboratory BC-adapted strain. The latter readily acquired the ability to grow in BC, and also exhibited physico-chemical surface changes. The existence of residues on PS surfaces altered their hydrophobicity and favoured adhesion as determined by the free energy and early adhesion characterization. Adapted bacteria revealed a higher ability to adhere to surfaces and to develop biofilms, especially on BC-conditioned surfaces, which thereby could enhance resistance to sanitation attempts. These findings highlight the importance of investigations concerning the antimicrobial deposition effect after cleaning procedures, which may encourage bacterial adhesion, especially of bacteria that have been previously exposed to chemical stresses. PMID- 22098458 TI - Implications for risk assessment. PMID- 22098459 TI - Structural, magnetic, and electronic properties of phenolic oxime complexes of Cu and Ni. AB - Square planar complexes of the type Ni(L(1))(2), Ni(L(2))(2), Cu(L(1))(2), and Cu(L(2))(2), where L(1)H = 2-hydroxy-5-t-octylacetophenone oxime and L(2)H = 2 hydroxy-5-n-propylacetophenone oxime, have been prepared and characterized by single-crystal X-ray diffraction, cyclic voltammetry, UV/vis spectroscopy, field effect-transistor measurements, density functional theory (DFT) and time dependent DFT (TDDFT) calculations, and, in the case of the paramagnetic species, electron paramagnetic resonance (EPR) and magnetic susceptibility. Variation of alkyl groups on the ligand from t-octyl to n-propyl enabled electronic isolation of the complexes in the crystal structures of M(L(1))(2) contrasting with pi stacking interactions for M(L(2))(2) (M = Ni, Cu). This was evidenced by a one dimensional antiferromagnetic chain for Cu(L(2))(2) but ideal paramagnetic behavior for Cu(L(1))(2) down to 1.8 K. Despite isostructural single crystal structures for M(L(2))(2), thin-film X-ray diffraction and scanning electron microscopy (SEM) revealed different morphologies depending on the metal and the deposition method (vapor or solution). The Cu complexes displayed limited electronic interaction between the central metal and the delocalized ligands, with more mixing in the case of Ni(II), as shown by electrochemistry and UV/vis spectroscopy. The complexes M(L(2))(2) showed poor charge transport in a field effect transistor (FET) device despite the ability to form pi-stacking structures, and this provides design insights for metal complexes to be used in conductive thin-film devices. PMID- 22098460 TI - CD48 as a novel molecular target for antibody therapy in multiple myeloma. AB - Monoclonal antibody (mAb) drugs are desirable for the improvement of multiple myeloma (MM) treatment. In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes. CD48 was only weakly expressed on some CD34(+) haematopoietic stem/progenitor cells, and not expressed on erythrocytes or platelets. We next examined whether CD48 could serve as a target antigen for mAb therapy against MM. A newly generated in-house anti-CD48 mAb induced mild antibody-dependent cell-mediated cytotoxicity and marked complement dependent cytotoxicity against not only MM cell lines but also primary MM plasma cells in vitro. Administration of the anti-CD48 mAb significantly inhibited tumour growth in severe combined immunodeficient mice inoculated subcutaneously with MM cells. Furthermore, anti-CD48 mAb treatment inhibited growth of MM cells transplanted directly into murine bone marrow. Finally and importantly, we demonstrated that the anti-CD48 mAb did not damage normal CD34(+) haematopoietic stem/progenitor cells. These results suggest that the anti-CD48 mAb has the potential to become an effective therapeutic mAb against MM. PMID- 22098461 TI - Administration of prednisolone intravenously or dexamethason orally in random donors reveals equal results in granulocyte collection: a single centre experience. AB - Since cytokine--mobilization for granulocyte collections in random donors--is not licensed in Austria, we investigated in a prospective analysis the effects of prednisolone or dexamethasone (DXM) in 153 donors (35 women/118 men) and in the collected products. Either prednisolone (50 mg) intravenously 4 h before granulocyte collection or DXM (8 mg) orally 12 h before collection was given. Collections were performed with the Cobe Spectra (CardianBCT, Lakewood). We recorded a significantly higher percentage of granulocytes in the peripheral blood of the DXM. However, the collected number of granulocytes was equal in both groups. PMID- 22098462 TI - Effects of high temperature stress at different development stages on soybean isoflavone and tocopherol concentrations. AB - Soybean contains a range of compounds with putative health benefits including isoflavones and tocopherols. A study was conducted to determine the effects on these compounds of high temperature stress imposed at specific development stages [i.e., none, pre-emergence, vegetative, early reproductive (R1-4), late reproductive (R5-8), or all stages]. Two cultivars (AC Proteina and OAC Champion) were grown in growth chambers set at contrasting temperatures [i.e., stress conditions of 33/25 degrees C (day/night temperature) and control conditions of 23/15 degrees C] in order to generate these treatments. Isoflavone and tocopherol concentrations in mature seeds were determined using high-performance liquid chromatography. In both cultivars isoflavone response was greatest when stress occurred during the R5-8 stages and during all development stages, these treatments reducing total isoflavone concentration by an average of 85% compared to the control. Stress imposed at other stages also affected isoflavone concentration although the response was smaller. For example, stress during the vegetative stages reduced total isoflavones by 33% in OAC Champion. Stress imposed pre-emergence had an opposite effect increasing daidzein concentration by 24% in AC Proteina. Tocopherol concentrations were affected the most when stress was imposed during all stages of development, followed by stress restricted to stages R5-8; response to stress during other stages was limited. The specific response of tocopherols differed, alpha-tocopherol being increased by high temperature by as much as 752%, the reverse being observed for delta-tocopherol and gamma-tocopherol. The present study demonstrates that while isoflavone and tocopherol concentrations in soybeans are affected the most by stress occurring during seed formation, concentrations can also be affected by stress occurring at other stages including stages as early as pre-emergence. PMID- 22098463 TI - Intensified daily dialysis: the best chronic dialysis option for children? AB - Children receiving chronic hemodialysis (HD) three times a week have many obstacles to overcome. Not only do they have to endure dietary restrictions, but they also need to take various medications on a daily basis, which contribute to anorexia. Children on such conventional dialysis programs often have poorly controlled blood pressure (which can lead to left ventricular hypertrophy and/or left ventricular dysfunction) and impaired statural growth. Therefore, the need for more frequent and/or intensive dialysis is recognized. Nevertheless despite limited center experience, daily dialysis is currently most often limited as a rescue treatment. When performed, daily intensified HD provides a modality for preserving cardiovascular health and promoting normal growth in children. Therefore, the time spent on chronic dialysis preserves their chances of the best possible outcome. PMID- 22098464 TI - Activated lymphocytes and high liver expression of IFN-gamma are associated with fulminant hepatic failure in patients. AB - BACKGROUND & AIMS: To study immunological mechanisms of fulminant hepatic failure (FHF) derived from extensive liver lesions, 14 patients with FHF induced by different aetiologies were investigated by observance of both lymphocyte phenotyping and cytokine levels. METHODS: Five patients bearing benign acute hepatitis B (AHB) and seven healthy liver donors (HC) were used as controls. Samples of liver and blood from both FHF patients and HC were obtained during transplantation procedures. Plasma levels of IL-1beta, IL-4, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, MCP-1, RANTES and MIP-1alpha were quantified using a multiplex immunoassay. Cell characterization was carried out by flow cytometry. IFN-gamma staining was performed on liver sections using immunofluorescence methods. RESULTS: An increase of peripheral frequency of natural killer (NK) cells expressing early activation markers (CD69, HLA-DR and CD38) and adhesion molecule CD44 was observed in FHF patients. Elevated frequency of T lymphocytes CD4(+) and CD8(+) expressing CD38 and adhesion molecules CD29 and CD44 was also observed in FHF. Additionally, an increase of natural killer T cells (NKT) was detected in FHF patients. High plasma cytokine levels were not statistically different between FHF and AHB patients. In comparison to HC, a strong liver expression of IFN-gamma was detected in FHF patients. The increased frequency of CD4(+) CD44(+) and IL-8 cytokine was found in patients with poor prognosis. CONCLUSIONS: These findings indicate the involvement of NK and NKT cells as well as T lymphocytes CD4(+) and CD8(+) in the inflammatory process inducing FHF, confirmed by the high hepatic expression of IFN-gamma. PMID- 22098465 TI - The biological basis of severe outcomes in Anaplasma phagocytophilum infection. AB - Anaplasma phagocytophilum causes granulocytic anaplasmosis, an acute disease in humans that is also often subclinical. However, 36% are hospitalized, 7% need intensive care, and the case fatality rate is 0.6%. The biological basis for severe disease is not understood. Despite A. phagocytophilum's mechanisms to subvert neutrophil antimicrobial responses, whether these mechanisms lead to disease is unclear. In animals, inflammatory lesions track with IFNgamma and IL 10 expression and infection of Ifng(-/-) mice leads to increased pathogen load but inhibition of inflammation. Suppression of STAT signaling in horses impacts IL-10 and IFN-gamma expression, and also suppresses disease severity. Similar inhibition of inflammation with infection of NKT-deficient mice suggests that innate immune responses are key for disease. With severe disease, tissues can demonstrate hemophagocytosis, and measures of macrophage activation/hemophagocytic syndromes (MAS/HPS) support the concept of human granulocytic anaplasmosis as an immunopathologic disease. MAS/HPS are related to defective cytotoxic lymphocytes that ordinarily diminish inflammation. Pilot studies in mice show cytotoxic lymphocyte activation with A. phagocytophilum infection, yet suppression of cytotoxic responses from both NKT and CD8 cells, consistent with the development of MAS/HPS. Whether severity relates to microbial factors or genetically determined diversity in human immune and inflammatory response needs more investigation. PMID- 22098467 TI - Noninfectious diverticulum of mitral valve causing severe mitral regurgitation. PMID- 22098466 TI - Discovery of a novel and potent class of F. tularensis enoyl-reductase (FabI) inhibitors by molecular shape and electrostatic matching. AB - Enoyl-acyl carrier protein (ACP) reductase, FabI, is a key enzyme in the bacterial fatty acid biosynthesis pathway (FAS II). FabI is an NADH-dependent oxidoreductase that acts to reduce enoyl-ACP substrates in a final step of the pathway. The absence of this enzyme in humans makes it an attractive target for the development of new antibacterial agents. FabI is known to be unresponsive to structure-based design efforts due to a high degree of induced fit and a mobile flexible loop encompassing the active site. Here we discuss the development, validation, and careful application of a ligand-based virtual screen used for the identification of novel inhibitors of the Francisella tularensis FabI target. In this study, four known classes of FabI inhibitors were used as templates for virtual screens that involved molecular shape and electrostatic matching. The program ROCS was used to search a high-throughput screening library for compounds that matched any of the four molecular shape queries. Matching compounds were further refined using the program EON, which compares and scores compounds by matching electrostatic properties. Using these techniques, 50 compounds were selected, ordered, and tested. The tested compounds possessed novel chemical scaffolds when compared to the input query compounds. Several hits with low micromolar activity were identified and follow-up scaffold-based searches resulted in the identification of a lead series with submicromolar enzyme inhibition, high ligand efficiency, and a novel scaffold. Additionally, one of the most active compounds showed promising whole-cell antibacterial activity against several Gram-positive and Gram-negative species, including the target pathogen. The results of a preliminary structure-activity relationship analysis are presented. PMID- 22098468 TI - Pilot application of iTRAQ to the retinal disease Macular Telangiectasia. AB - We used the comparative proteomic technique iTRAQ coupled with offline 2DLC-MS/MS to analyze a rare specimen of the poorly understood, potentially blinding ophthalmic condition Macular Telangiectasia type 2 (MacTel type 2). We refined the technique using an internal standard consisting of pooled samples for each iTRAQ experiment to allow for multiple comparisons between different regions of the retina and different tissue donors. A total of 594 nonredundant proteins were identified in the retina and 168 in the vitreous, of which approximately half were found in significantly different abundance in the various comparisons made. The most prominent differences were found within the glycolytic pathway, where 8 proteins were reduced in the diseased macula compared with peripheral retina of the same eye, and 10 were also reduced in comparison with the macula of a control eye. Furthermore, Muller cell-associated proteins, including GFAP, VIME, and GLNA, were also reduced in the diseased macula, consistent with a link between the glycolytic pathway and Muller cells. These changes were validated by Western blotting and immunohistochemical studies. Proteomic analysis of the vitreous revealed an increase of proteins that were reduced in the retina. This supports proteomic analysis of the more easily available vitreous, which may reveal retina specific protein changes associated with disease. Furthermore, our study has highlighted changes in the glycolytic pathway as a possible component of MacTel type 2 pathobiology. PMID- 22098470 TI - NSC 74859-mediated inhibition of STAT3 enhances the anti-proliferative activity of cetuximab in hepatocellular carcinoma. AB - BACKGROUND: Cetuximab [an epidermal growth factor receptor (EGFR) inhibitor], which was shown to be effective in rectal and non-small cell lung cancers (NSCLCs), was only modestly effective in clinical trials of hepatocellular carcinoma (HCC). STAT3, which is thought to be a determinant of HCC sensitivity to antitumour drugs, may be involved. AIMS: To evaluate the efficacy of combination therapy using cetuximab and NSC 74859 (a novel STAT3 inhibitor) in EGFR and STAT3 overexpressing hepatoma cells. METHODS: Hepatoma cell lines were treated with cetuximab, NSC 74859 or a combination of both drugs. Efficacy of treatment was evaluated by determining cell viability using MTT assays and proliferation by cell counting. Expression and activation of STAT3 were determined using Western blot analysis. We evaluated the role of STAT3 in single and combination therapy using siRNA-mediated knock-down of STAT3 or STAT3 overexpression strategies. RESULTS: HepG2 and Huh-7 cells, which had lower levels of pSTAT3 than SK-HEP1 cells, were more sensitive to cetuximab treatment when compared with SK-HEP1 cells. Although none of these cell lines was sensitive to NSC 74859 alone, NSC 74859 potentiated the antiproliferative effect of cetuximab in all three cell lines. siRNA knock-down of STAT3 increased the sensitivity of these cell lines to cetuximab, whereas STAT3 overexpression antagonized these effects. CONCLUSIONS: Enhanced growth inhibition in hepatoma cells treated with both NSC 74859 and cetuximab suggests that cetuximab resistance is probably mediated via STAT3. Combination therapy using both inhibitors of EGFR and STAT3 signalling warrants further investigation under in vivo condition. PMID- 22098471 TI - The distribution of fibrillin-2 and LTBP-2, and their co-localisation with fibrillin-1 in adult bovine tail disc. AB - We investigated the distribution of fibrillin-2 and LTBP-2 (latent TGF-beta binding protein-2) in the intervertebral disc of the adult bovine tail. The association of fibrillin-2 and of LTBP-2 with fibrillin-1 was examined by dual immunofluorescence staining. Both fibrillin-2 and LTBP-2 were found extensively distributed in all regions of the disc with the organisation of the network varying significantly region to region. In the outer annulus fibrosus (OAF) both fibrillin-2 and LTBP-2 co-localised with fibrillin-1 forming fibres running parallel to the collagen fibres of the lamellae with the microfibrillar network staining densely in between the adjacent lamellae and also at the boundaries of the collagen bundle compartments. In the inner annulus fibrosus (IAF) and nucleus pulposus (NP), co-localised fibrillin-1,2 and LTBP-2 formed a chondron-like structure around the cell. By contrast, the inter-territorial matrix of the IAF and NP contained a dense network of fibrillin-2 but only sparse/filamentous fibres of fibrillin-1 and LTBP-2. Dual immunostaining revealed that in this region, fibrillin-2 was highly colocalised with elastin. The LTBP-2 network co localised well with that of fibrillin-1 in all regions and indeed is reported to bind strongly to fibrillin-1. However, interestingly LTBP-2 but not fibrillin-1 or fibrillin-2 was removed by hyaluronidase but not collagenase pre-digestion. Our results suggest that fibrillin-2 and LTBP-2 could play an important role in disc function. PMID- 22098472 TI - Saxagliptin and sitagliptin in adult patients with type 2 diabetes: a systematic review and meta-analysis. AB - The objective of this study is to compare the efficacy and safety of sitagliptin and saxagliptin with placebo and other hypoglycaemic medications in adults with type 2 diabetes. We searched MEDLINE(r), Embase, the Cochrane Library and the International Pharmaceuticals from their inception through 3 February 2011. Studies were included of adults with type 2 diabetes that were 12 weeks or more in duration. Meta-analyses were conducted when included studies were homogenous enough to justify combining their results. A total of 32 articles met inclusion criteria. Sitagliptin 100 mg monotherapy and saxagliptin 5 mg resulted in greater HbA1c reduction compared to placebo [weighted mean difference (WMD) -0.82%, 95% CI -0.95 to -0.70 and WMD -0.70, 95% CI -0.84 to -0.56, respectively]. Sitagliptin was similar to sulfonylureas for HbA1c reduction (WMD 0.08%, 95% CI 0 0.16, 3 trials) and to saxagliptin in one head-to-head trial. There was no statistically significant difference in hypoglycaemia between sitagliptin (pooled RR 1.55, 95% CI 0.55-4.36) or saxagliptin (pooled RR 1.04, 95% CI 0.28-3.81) and placebo. Sitagliptin and saxagliptin result in similar modest HbA1c reductions and do not increase the risk of hypoglycaemia unless combined with other therapies. Their role in the long-term treatment of type 2 diabetes remains unclear given the lack of long-term data on efficacy, harms and health outcomes. PMID- 22098473 TI - Aging and temporal order memory: a comparison of direct and indirect measures. AB - The purpose of the present study is to compare the effect of aging on direct and indirect measures of temporal order memory, derived from the Rey Auditory Verbal Learning Test (AVLT). The spontaneous order in which the list was recalled in Trial 5 served as the indirect measure, and the explicit reordering of the words into their original order of presentation (i.e., Trial 10) served as the direct measure. Based on previously reported norms (n = 528) on the Rey AVLT, the effects of age (20-91 years) on the two measures of temporal order were analyzed. The results demonstrated that the direct measure was much more sensitive to the effect of age than the indirect measure. Furthermore, the direct measure was more significantly correlated with other verbal memory measures derived from the Rey AVLT. These results are consistent with studies that have documented that the frontal lobes, implicated in temporal memory, show the most significant degenerative changes over the years. As a result, the effortful and direct cognitive tasks in general and particularly in memory are more vulnerable to the effects of aging. These results lend further support to the dissociation between direct and indirect measures of memory in older adults. These temporal order measures, which are not usually assessed in standard batteries, could now be derived from a standard, frequently used test (i.e., Rey AVLT) and increase its diagnostic value. PMID- 22098474 TI - Optical detection of brain function: simultaneous imaging of cerebral vascular response, tissue metabolism, and cellular activity in vivo. AB - It is known that a remaining challenge for functional brain imaging is to distinguish the coupling and decoupling effects among neuronal activity, cerebral metabolism, and vascular hemodynamics, which highlights the need for new tools to enable simultaneous measures of these three properties in vivo. Here, we review current neuroimaging techniques and their prospects and potential limitations for tackling this challenge. We then report a novel dual-wavelength laser speckle imaging (DW-LSI) tool developed in our labs that enables simultaneous imaging of cerebral blood flow (CBF), cerebral blood volume, and tissue hemoglobin oxygenation, which allows us to monitor neurovascular and tissue metabolic activities at high spatiotemporal resolutions over a relatively large field of view. Moreover, we report digital frequency ramping Doppler optical coherence tomography (DFR-OCT) that allows for quantitative 3D imaging of the CBF network in vivo. In parallel, we review calcium imaging techniques to track neuronal activity, including intracellular calcium approach using Rhod2 fluorescence technique that we develop to detect neuronal activity in vivo. We report a new multimodality imaging platform that combines DW-LSI, DFR-OCT, and calcium fluorescence imaging for simultaneous detection of cortical hemodynamics, cerebral metabolism, and neuronal activities of the animal brain in vivo, as well as its integration with microprobes for imaging neuronal function in deep brain regions in vivo. Promising results of in vivo animal brain functional studies suggest the potential of this multimodality approach for future awake animal and behavioral studies. PMID- 22098475 TI - Heterosis for carotenoid concentration and profile in maize hybrids. AB - Production of high-lutein maize grain is of particular interest as a value-added feed source to produce high-lutein eggs. In this paper, it is demonstrated that heterosis for total carotenoid concentration and for the ratio of lutein to zeaxanthin (L:Z ratio), or profile type, exists infrequently in yellow dent crosses. However, yellow dent inbred maize lines A619 and CG102, both possessing high-lutein profiles, produce F1 seed with a classic overdominant expression of lutein levels (i.e., 49 ug/g dry weight (DW) above the high-parent value). Reciprocal crosses of A619 and CG102 with one another and with two high zeaxanthin (i.e., low lutein), high-carotenoid lines both suggest that the A619 and CG102 high-lutein phenotypes are achieved by different and complementary genotypes. The contribution of CG102 to the heterotic response was examined using a QTL-based approach that involved phenotyping the mapping population in a testcross to A619. Significant QTL were found at loci known to be involved in the carotenoid pathway but also at loci proximate to, but separate from, known carotenoid pathway steps. Exploiting an overdominant heterotic response for lutein and total carotenoids should be given strong consideration as a viable method of producing high-carotenoid hybrid maize lines. PMID- 22098476 TI - Aqueous garlic extract and its phytochemical profile; special reference to antioxidant status. AB - Garlic (Allium sativum L) has distinct nutritional profile with special reference to its bioactive components and is used in different diet-based therapies to cure various lifestyle-related disorders. For this purpose, characterization and extraction of garlic were carried out followed by antioxidant assays. Different solvents (50% aqueous ethanol, 50% aqueous methanol and water) at different time intervals (4, 5 and 6 h) at 60 degrees C were used to optimize aqueous extraction efficiency of garlic. Among the solvents, water extract resulted in better extraction yield (31.85 +/- 2.09 g/25 g) at 5 h. The antioxidant potential of all these solvents was estimated through in vitro studies. In this context, it was observed that higher amount of total phenolic contents was present in aqueous methanol 71.87 +/- 1.69% at 45 min. Antiradical (1,1-diphenyl-2-picrylhydrazyl assay) and antioxidant activity showed that the maximum value was 73.80 +/- 3.69 and 83.83 +/- 0.16%, respectively, in methanolic extract at 45 min while glucose diffusion and ferric reducing antioxidant power were 97.00 +/- 0.20 and 32.66 +/- 0.72% at p < 0.05, respectively. Aqueous garlic extract was selected as the best treatment on the basis of percentage yield and safety modulation in human body absorption. Aqueous garlic extract was subjected to pH, acidity, total soluble solids (TSS) and colour. It was observed that the pH of aqueous garlic extract decreased with the passage of time while acidity increased. It was also concluded that storage affected the value of TSS and colour significantly. L* values for colour on 0 day were 34.18 +/- 0.08, whereas those on 28th day were 38.84 +/- 0.03. It was predicted that 28 days storage resulted in significant increase in L* value, while a* value decreased from 4.31 +/- 0.01 to 0.32 +/- 0.01 at the end of storage study. PMID- 22098477 TI - Bidirectional pattern-specific plasticity of the slow afterhyperpolarization in rats: role for high-voltage activated Ca2+ channels and I h. AB - A burst of action potentials in hippocampal neurons is followed by a slow afterhyperpolarization (sAHP) that serves to limit subsequent firing. A reduction in the sAHP accompanies acquisition of several types of learning, whereas increases in the sAHP are correlated with cognitive impairment. The present study demonstrates in vitro that activity-dependent bidirectional plasticity of the sAHP does not require synaptic activation, and depends on the pattern of action potential firing. Whole-cell current-clamp recordings from CA1 pyramidal neurons in hippocampal slices from young rats (postnatal days 14-24) were performed in blockers of synaptic transmission. The sAHP was evoked by action potential firing at gamma-related (50 Hz, gamma-AHP) or theta frequencies (5 Hz, theta-AHP), two firing frequencies implicated in attention and memory. Interestingly, when the gamma-AHP and theta-AHP were evoked in the same cell, a gradual potentiation of the gamma-AHP (186 +/- 31%) was observed that was blocked using Ca(2+) channel blockers nimodipine (10 MUm) or omega-conotoxin MVIIC (1 MUm). In experiments that exclusively evoked the sAHP with 50 Hz firing, the gamma-AHP was similarly potentiated (198 +/- 44%). However, theta-burst firing pattern alone resulted in a decrease (65 +/- 19%) of the sAHP. In these experiments, application of the h channel blocker ZD7288 (25 MUm) selectively prevented enhancement of the gamma AHP. These data demonstrate that induction requirements for bidirectional AHP plasticity depend on the pattern of action potential firing, and result from distinct mechanisms. The identification of novel mechanisms underlying AHP plasticity in vitro provides additional insight into the dynamic processes that may regulate neuronal excitability during learning in vivo. PMID- 22098478 TI - Tumor local chemohyperthermia using docetaxel-embedded magnetoliposomes: Interaction of chemotherapy and hyperthermia. AB - BACKGROUND AND AIM: We have studied and reported the usefulness of tumor local chemohyperthermia at a low-grade temperature below 43 degrees C with docetaxel embedded magnetoliposome (DML) and an applied alternating current magnetic field. However, the mechanisms of this treatment and the dynamics of the injected docetaxel were not investigated in our previous study. Thus, we investigated the interaction of chemotherapy and hyperthermia in the treated tumor. METHODS: Human MKN45 gastric cancer cells were implanted in the hind limbs of Balb-c/nu/nu mice. DML, magnetite-loaded liposome, and docetaxel were injected into the tumors with or without being exposed to an alternating current magnetic field. Docetaxel and tumor necrosis factor-alpha concentrations, the cell cycle, and cell death rates in the tumor were examined. RESULTS: Docetaxel concentrations were significantly higher in the DML-injected group than in the docetaxel-injected group 3 days after injection. A G2/M peak was observed 1 day after treatment in the DML injected and exposed group and the docetaxel-injected group, while it was observed 3 days after treatment in the DML-injected without heating group and the magnetite-loaded liposome group. The tumor cell death rate gradually increased in the DML-injected group, with or without being exposed, while it gradually decreased after its peak in other groups. The tumor necrosis factor-alpha concentration in the tumor treated with DML with heating remained at a high level on the 7th day after treatment, while it decreased after its peak in other groups. CONCLUSION: The antitumor effect of this treatment derives from a combination of hyperthermia and chemotherapy locally in the tumor. PMID- 22098479 TI - An integrative review of interventions promoting self-care of patients with heart failure. AB - AIM AND OBJECTIVE: To examine the interventions used to improve self-care of heart failure patients. The specific objectives were to examine the efficacy of interventions to improve heart failure self-care (self-maintenance and self management behaviours) and patient-related factors such as knowledge about heart failure, self-efficacy for heart failure self-care (confidence) and beliefs regarding heart failure self-care. BACKGROUND: Despite the significant advances in the treatment and management of heart failure, there continues to be poor patient outcomes associated with this clinical syndrome. DESIGN: An integrative review. METHOD: A search of MEDLINE, PsychINFO, Cochrane data base of clinical trials and the cumulative index of nursing and allied health literature (CINAHL) databases was conducted using 14 search terms for a period from 2000-2010. Hand searching of reference lists and author lists was also conducted. Nineteen eligible self-care intervention studies were included in this review. RESULTS: Cognitive-behavioural intervention mechanisms were most frequently used to improve patient's heart failure self-care. In the majority of the studies, the interventions demonstrated efficacy by improving heart failure patients' self care maintenance and management behaviours. Intervention group subjects, in the majority of studies, had significantly higher levels of knowledge pertaining to heart failure and heart failure related self-care. RELEVANCE TO CLINICAL PRACTICE: Based on these findings, there are improved patient outcomes when standard patient education for heart failure is augmented using cognitive behavioural strategies that include additional evidence-based education and counselling. PMID- 22098480 TI - Identification and characterization of low molecular weight polyphenols in berry leaf extracts by HPLC-DAD and LC-ESI/MS. AB - This paper reports the results of qualitative and quantitative analyses of low molecular weight phenolics from five berry leaf extract using HPLC-DAD and LC ESI/MS. The identification of the black currant, raspberry, bilberry, honeysuckle, and strawberry leaf phytochemicals was based on the comparison of UV vis absorption maxima (lambda(max)) and mass spectral analysis. The peak identification in samples was also based on comparisons of the retention times (t(R)) of the isolated phytochemical standards. Knowledge of the precise phenolic profile of berry leaves may offer a scientific basis to put the underutilized berry leaves to good use as very cheap raw materials for polyphenol extract production. These studies indicated that these leaves can be used as a good and cheap source of bioactive constituents. These results suggest that berry leaves are a potential source of phenolics and have potential pro-healthy properties to contribute to human health. PMID- 22098481 TI - Enhancement of the mechanical properties of directly spun CNT fibers by chemical treatment. AB - Translating the remarkable mechanical properties of individual carbon nanotubes to macroscopic assemblies presents a unique challenge in maximizing the potential of these remarkable entities for new materials. Infinitely long individual nanotubes would represent the ideal molecular building blocks; however, in the case of length-limited nanotubes, typically in the range of micro- and millimeters, an alternative strategy could be based on the improvement of the mechanical coherency between bundles assembling the macroscopic materials, like fibers or films. Here, we present a method to enhance the mechanical performance of fibers continuously spun from a CVD reactor, by a postproduction processing methodology utilizing a chemical agent aided by UV irradiation. The treatment results in an increase of 100% in specific strength and 300% in toughness of the fibers with strength values rocketing to as high as 3.5 GPa SG(-1). An attempt has been made to explore the nature of the chemical modifications introduced in the fiber and the consequential effects on its properties. PMID- 22098482 TI - Expression of multiple cytokines and CCR4 in primary testicular diffuse large B cell lymphoma, not otherwise specified, involving the skin. PMID- 22098483 TI - Visual acuity changes in cone and cone-rod dystrophies. AB - PURPOSE: The purpose of the study was to evaluate longitudinal visual acuity (VA) changes in cone (CD) and cone-rod dystrophies (CRD) in order to develop recommendations for follow-up strategies and to define an optimal time for potential therapeutic intervention. METHODS: Patients with clinically defined CD and CRD, who had at least three clinical examinations within a follow-up period of a minimum of 2 years, were included in the study. The observation period was divided into segments: between 1-2 visits and 2-3 visits in intervals of 2 years, and between 3-4 visits in 3-year intervals. Disease history was collected during the baseline examination. Median age of onset, age at first examination, and period between disease onset and 1st visit (latency) were estimated. Medians with 25th and 75th quantile of VA decrease in logMAR for each segment of observation were calculated. The median percentage of VA decrease was also calculated. RESULTS: Initial results of the Tuebingen longitudinal study of VA changes in CRD and CD are presented as medians with 25th and 75th quintiles. Twenty-nine patients (14 men and 15 women) were studied. Nineteen of them had CRD and 10 CD. Median age at the baseline visit was 18 (11, 31) years for CRD and 26 (8, 41.5) years for CD. Median age of disease onset was 9 (8, 25) years for CRD and 7.5 (5, 15) years for CD. The median latency was 6.5 (3; 8.25) years in CD and 4 (2, 10) years in CRD patients. VA in CD and CRD patients was significantly different only during the first visit (p < 0.03). VA decrease was highest in the period between 2-3 visits with a median VA decrease of 36%, for CDR and between 3-4 visits for CD with a median VA decrease of 80%. In the CRD group the rate of VA decline was fairly even over the four visits, whereas in the CD group the decline appeared to progressively increase towards the end of the follow-up. CONCLUSION: CRD patients were younger than those with CD at a baseline visit and had a longer period of follow-up. A statistically significant difference in VA in CRD and CD was observed at the first ophthalmological examination only. VA decrease was most prominent in the second decade of life in CRD and in third decade in CD patients. CRD was characterized by a more progressive VA decrease than CD. CRD had a high decline of VA over the second and the third examination, whereas VA decline in CD progressed towards the end of follow-up period (fourth examination). These results should be considered when advising and following up such patients on a long-term basis. PMID- 22098484 TI - Synthesis, structural characterization, photophysical, electrochemical, and anion sensing studies of luminescent homo- and heteroleptic ruthenium(II) and osmium(II) complexes based on terpyridyl-imidazole ligand. AB - A series of hetero- and homoleptic tridentate ruthenium(II) and osmium(II) complexes of compositions [(tpy-PhCH(3))Ru(tpy-HImzphen)](ClO(4))(2) (1), [(H(2)pbbzim)Ru(tpy-HImzphen)](ClO(4))(2) (2), and [M(tpy HImzphen)(2)](ClO(4))(2) [M = Ru(II) (3) and Os(II) (4)], where tpy-PhCH(3) = 4' (4-methylphenyl)-2,2':6',2"-terpyridine, H(2)pbbzim = 2,6-bis(benzimidazole-2 yl)pyridine and tpy-HImzphen = 2-(4-[2,2':6',2"]terpyridine-4'-yl-phenyl)-1H phenanthro[9,10-d]imidazole, have been synthesized and characterized by using standard analytical and spectroscopic techniques. X-ray crystal structures of three complexes 2, 3, and 4 have been determined. The absorption spectra, redox behavior, and luminescence properties of the complexes have been thoroughly investigated. All of the complexes display moderately strong luminescence at room temperature with lifetimes in the range of 10-55 ns. The effect of solvents on the absorption and emission spectral behavior of the complexes has also been studied in detail. The anion sensing properties of all the complexes have been studied in solution using absorption, emission, and (1)H NMR spectral studies and by cyclic voltammetric (CV) measurements. It has been observed that the complexes 1, 3, and 4 act as sensors for F(-)only, whereas 2 acts as sensor for F(-), AcO( ), and to some extent for H(2)PO(4)(-). It is evident that in the presence of excess of anions deprotonation of the imidazole N-H fragment(s) occurs in all cases, an event which is signaled by the development of vivid colors visible with the naked eye. The receptor-anion binding/equilibrium constants have been evaluated. PMID- 22098485 TI - Decoding the roles of pilotins and accessory proteins in secretin escort services. AB - Secretins are channels that allow translocation of macromolecules across the outer membranes of Gram-negative bacteria. Virulence, natural competence, and motility are among the functions mediated by these large oligomeric protein assemblies. Filamentous phage also uses secretins to exit their bacterial host without causing cell lysis. However, the secretin is only a part of a larger membrane-spanning complex, and additional proteins are often required for its formation. A class of outer membrane lipoproteins called pilotins has been implicated in secretin assembly and/or localization. Additional accessory proteins may also be involved in secretin stability. Significant progress has recently been made toward deciphering the complex interactions required for functional secretin assembly. To allow for easier comparison between different systems, we have classified the secretins into five different classes based on their requirements for proteins involved in their assembly, localization, and stability. An overview of pilotin and accessory protein structures, functions, and characterized modes of interaction with the secretin is presented. PMID- 22098486 TI - Intra- and inter-session reliability of vertical jump performance in healthy middle-aged and older men and women. AB - Despite its widespread use in performance assessment, the reliability of vertical jump in an ageing population has not been addressed properly. The aim of the present study was to assess intra- and inter-day reliability of countermovement jump in healthy middle-aged (55-65 years) and older (66-75 years) men and women. Eighty-two participants were recruited and asked to perform countermovement jumps on two different occasions interspersed by 4 weeks. The middle-aged groups exhibited excellent absolute reliability for flight height, jump height, peak force, peak power, peak force/body mass, and peak power/body mass, with coefficients of variation ranging from 2.9% to 7.2% in men and from 3.6% to 6.9% in women and moderate-to-high intraclass correlations (0.75 to 0.97 in men; 0.77 to 0.95 in women). The older groups displayed good coefficients of variation (4.2% to 10.8% in men and 3.4% to 9.5% in women), but the intraclass correlations were low-to-high (0.43 to 0.84 in men; 0.42 to 0.93 in women). Overall, intra session reliability was higher than inter-session reliability. Peak power was by far the most consistent variable, whereas flight and jump height had the most marked variability. The minimum detectable change varied from 10.5% to 33%, depending on the variable examined, suggesting important implications for intervention studies. PMID- 22098487 TI - The natural history of hepatitis C virus infection acquired during childhood. AB - BACKGROUND: The outcome of patients with hepatitis C virus (HCV) infection acquired during childhood in the absence of antiviral therapy is not clear. AIMS: The purpose of this study was to review the outcome of untreated HCV acquired in childhood. Only population-based studies were included, as referred cases would be predicted to have more severe disease. METHODS: A systematic review of the literature was completed up to October 2010 to identify studies where a population was screened for HCV infection that was presumably acquired during childhood. Demographical and clinical data were collected on infected patients who had not been treated with an antiviral. Primary outcome was development of a severe adverse outcome (cirrhosis, hepatoma, need for a liver transplant or liver related death). RESULTS: There were 25 studies reporting a total of 733 infected patients. Liver biopsy results were provided for 180 patients (25%), revealing cirrhosis in eight (1.0% of the total and 4.0% of those who had a biopsy). None of the other patients developed a severe adverse outcome. As a result of the small number of patients with a severe adverse outcome, risk factors for HCV progression could not be identified. CONCLUSION: Although HCV can lead to liver transplantation and death during childhood, the vast majority of patients with disease acquired during childhood have slowly progressive disease. There is no clear indication for antiviral therapy in the majority of children with HCV infection. PMID- 22098488 TI - Freezing 'stem cells' in a bag and tube under various freezing conditions? PMID- 22098489 TI - The indirect consequences of a mutualism: comparing positive and negative components of the net interaction between honeydew-tending ants and host plants. AB - 1. In ecological webs, net indirect interactions between species are composed of interactions that vary in sign and magnitude. Most studies have focused on negative component interactions (e.g. predation, herbivory) without considering the relative importance of positive interactions (e.g. mutualism, facilitation) for determining net indirect effects. 2. In plant/arthropod communities, ants have multiple top-down effects via mutualisms with honeydew-producing herbivores and harassment of and predation on other herbivores; these ant effects provide opportunities for testing the relative importance of positive and negative interspecific interactions. We manipulated the presence of ants, honeydew producing membracids and leaf-chewing beetles on perennial host plants in field experiments in Colorado to quantify the relative strength of these different types of interactions and their impact on the ant's net indirect effect on plants. 3. In 2007, we demonstrated that ants simultaneously had a positive effect on membracids and a negative effect on beetles, resulting in less beetle damage on plants hosting the mutualism. 4. In 2008, we used structural equation modelling to describe interaction strengths through the entire insect herbivore community on plants with and without ants. The ant's mutualism with membracids was the sole strong interaction contributing to the net indirect effect of ants on plants. Predation, herbivory and facilitation were weak, and the net effect of ants reduced plant reproduction. This net indirect effect was also partially because of behavioural changes of herbivores in the presence of ants. An additional membracid manipulation showed that the membracid's effect on ant activity was largely responsible for the ant's net effect on plants; ant workers were nearly ten times as abundant on plants with mutualists, and effects on other herbivores were similar to those in the ant manipulation experiment. 5. These results demonstrate that mutualisms can be strong relative to negative direct interspecific interactions and that positive interactions deserve attention as important components of ecological webs. PMID- 22098490 TI - Neuro-inflammatory sequelae of minimal trauma in the non-traumatized human brain. A microdialysis study. AB - Cytokine measurement directly from the brain parenchyma by means of microdialysis has documented the activation of certain procedures in vivo, after brain trauma in humans. However, the intercalation of the micro-catheter insertion with the phenomena triggered by the head trauma renders the assessment of the findings problematic. The present study attempts to elucidate the pure effect of minimal trauma, represented by the insertion of the micro-catheter, on the non traumatized human brain. Microdialysis catheters were implanted to twelve patients with drug-resistant epilepsy, subjected to invasive electroencephalogram recording with intracranial electrodes. Samples were collected during the first 5 days of monitoring. The dialysate was analyzed using bead flow cytometry, and the concentrations of IL-1, IL-6, IL-8, IL-10, IL-12, and TNFa were measured. The levels of IL-1 and IL-8 were found raised until 48 hours post-implantation and thereafter they reached a plateau of presumably basic values. The temporal profile of the IL-6 variation was different, the raise being much prolonged, as its concentration had not returned to basic levels at the fifth day post insertion. TNFa was found significantly raised only 2 hours after the implantation. Interleukins 10 and 12 did not present any significant response to micro-trauma. These findings, probably more clearly detected in an environment disengaged by the sequelae of severe brain injury, imply that the reaction of the neuro-inflammatory mechanisms of the brain exists even after minimal trauma and is unexpectedly intense concerning IL-6. This response concerns also IL-1, IL-8 and TNFa, while IL-10 and IL-12 may necessitate more severe injuries to be activated. An approach to the question of basic cytokine levels in the normal brain parenchyma is attempted. Finally, questions may rise regarding the objectivity of findings attributed by some studies to inflammatory perturbation after head injury. PMID- 22098491 TI - Hypoxic hepatitis. AB - Hypoxic hepatitis (HH), an acute liver injury also known as 'ischaemic hepatitis' or 'shock liver', is frequently observed in intensive care units. HH is heralded by a massive but transient rise in serum aminotransferase activities caused by anoxic necrosis of centrilobular liver cells. Cardiac failure, respiratory failure and toxic-septic shock are the main underlying conditions accounting for more than 90% of cases, but HH may also occur in other circumstances. Until recently, liver ischaemia, i.e. a drop in hepatic blood flow, was considered the leading, and even the sole, hemodynamic mechanism responsible for HH, and it was generally held that a shock state was required. In reality, other hemodynamic mechanisms of hypoxia, such as passive congestion of the liver, arterial hypoxaemia and dysoxia, play an important role while a shock state is observed in only 50% of cases. Accordingly, 'ischaemic hepatitis' and 'shock liver' are misnomers. Therapy of HH depends primarily on the nature of the underlying condition. The prognosis is poor, with more than half of patients dying during the hospital stay. PMID- 22098492 TI - Three-dimensional echocardiographic evaluation of the Fontan conduit for thrombus. AB - INTRODUCTION: Total caval pulmonary connection (Fontan circuit) is the final common pathway for the palliation of single ventricle congenital heart disease. Flow within the Fontan circuit results in an environment that is prone to thrombus formation putting the patient at risk for pulmonary and/or systemic embolus. To prevent these problems, patients are placed on antithrombotic therapy and periodically evaluated for thrombus within the conduit. Two-dimensional (2D) echocardiography, although commonly used to evaluate these patients, has been shown to have limited ability in accurately identifying thrombi within the Fontan conduit. The diagnosis of intracardiac thrombi has been augmented by three dimensional (3D) echocardiography and the patients in this series were evaluated with 3D imaging (3D transthoracic echocardiography and/or 3D transesophageal echocardiography) to determine if thrombi could be detected or excluded within the Fontan conduit. To the author's knowledge, this constitutes the first case series describing the use of 3D echocardiography to evaluate the Fontan conduit for thrombus. METHODS: The four patients described in this case series underwent 3D echocardiography to evaluate the Fontan conduit for a suspected or potential thrombus. RESULTS: The Fontan conduit was imaged and thrombi were felt to be documented or excluded in all four patients with 3D echocardiography. CONCLUSIONS: Three-dimensional echocardiography may enhance the ability to detect or exclude thrombi within the Fontan conduit. Further studies are needed to determine if this will prove to be an effective and reliable technique in evaluating the Fontan conduit for thrombus. PMID- 22098493 TI - Challenges and expectations of the Mental Capacity Act 2005: an interview-based study of community-based specialist nurses working in dementia care. AB - AIMS: This study aimed to explore experiences of specialist community nurses providing information about the Mental Capacity Act and supporting people with dementia and carers. BACKGROUND: The role of specialist community nurses and case managers, such as Admiral Nurses, suggests that providing information about the recent Mental Capacity Act (2005) in England and Wales would be appreciated by people with dementia and carers and would assist in assessment and support. DESIGN: In-depth qualitative methodology was adopted to explore experiences and opinions of Admiral Nurses using the Mental Capacity Act. METHOD: A volunteer sample of 15 Admiral Nurses were interviewed in 2008 about their experiences of explaining the legal framework to carers and people with dementia and expectations of the Act. Thematic analysis identified textual consistencies in the interviews. RESULTS: Most participants reported positively about the Mental Capacity Act and considered it beneficial when working with people with dementia and carers. Specific themes included knowledge acquisition and training, alongside limited confidence with implementation; practice experiences in the community and the empowering nature of the Mental Capacity Act; practice expectations and challenges with implementation. CONCLUSION: The Mental Capacity Act has potential for supporting the safeguarding and empowerment role of community nurses. However, not all participants felt confident using it and speculated this would improve with greater familiarity and use, which should be facilitated by refresher training and supervision. RELEVANCE TO CLINICAL PRACTICE: The article concludes that nurses providing support to carers and of people with dementia may need greater familiarity about legal provisions. This may assist them in providing general information, making timely referrals to sources of specialist legal advice, and in using the Act to reduce anxiety, conflict and disputes. PMID- 22098494 TI - Cyclic hydroxyamidines as amide isosteres: discovery of oxadiazolines and oxadiazines as potent and highly efficacious gamma-secretase modulators in vivo. AB - Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to be metabolically stable and to possess highly desirable pharmacokinetic profiles. These designs were applied in the identification of gamma-secretase modulators leading to highly efficacious agents for reduction of central nervous system Abeta(42) in various animal models. PMID- 22098495 TI - Biological determinants of bleeding in patients with heterozygous factor XI deficiency. AB - Bleeding risk is not predictable in patients with factor XI (FXI; F11) deficiency. In this prospective study, our objectives were to determine the biological determinants for bleeding risk in patients with heterozygous FXI deficiency. Patients were classified as either bleeding patients or non-bleeding patients by calculating the bleeding score (BS) described for von Willebrand disease. Primary haemostasis, thrombin generation, thromboelastometry, procoagulant proteins, inhibitors, fibrinolysis, and F11 gene mutations were compared between bleeding and non-bleeding patients. Thirty-nine patients were included. BS significantly correlated with clinical assessment (P=0.001), and a score over 3 discriminated between bleeding (n=15) and non-bleeding (n=24) patients (P=0.034). Despite normal values, von Willebrand factor (VWF) and thrombomodulin (TM) plasma levels were significantly lower in bleeding patients than non-bleeding patients [ristocetin cofactor activity (VWF:RCo)=80.6+/-29.7 iu/dl and 101.8+/-29.5iu/dl respectively, P=0.043; and VWF antigen (VWF:Ag)=84.0+/-28.0 iu/dl and 106.3+/-36.1 iu/dl respectively, P=0.035; and TM=17.7+/-11.7ng/ml and 23.6+/-9.7ng/ml respectively, P=0.043]. When considering BS as a continuous variable, only VWF:RCo remained significant (P=0.042), which accounted for 11% of the variability in BS. PMID- 22098496 TI - Occurrence and profiles of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in soils from a typical e-waste recycling area in Southeast China. AB - Surface soils collected from Taizhou, a typical e-waste recycling area in Southeast China, were analyzed for the residues of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) by using microwave-assisted extraction and gas chromatography mass spectrometry (GC-MS). The total concentrations of 16 PAHs in US EPA's priority list (SigmaPAHs), six indicator PCBs (SigmaPCBs), 15 OCPs widely used in China (SigmaOCPs) in soils ranged from 125 to 4737 ng/g (average: 854 ng/g), from not detected to 55.4 ng/g (3.16 ng/g), and from 47.9 to 820 ng/g (276 ng/g), respectively. Individual PAHs were ubiquitously found in soil samples with detected ratio of 96% and their residual levels were comparable with those of serious polluted sites. Principal component analysis in combination with diagnostic ratios suggested that the combustion of coal, wood, and plastic wastes that are closely associated with illegal and unsafe recycling operations of e wastes was the main source of PAHs in this area. Compared with other polluted sites, the PCBs residues in soils were generally low except for those in the major recycling site. The residual levels of OCPs in this region were also relatively higher and hexachlorocyclohexane (HCH), dichlorodiphenyltrichloroethane (DDT) and its metabolite forms including dichlorodiphenyldichloroethane (DDD) and dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and dicofol were dominant species. The composition analysis indicated that the HCHs residues in soils might originate from the application of lindane (pure gamma-HCH) and parts of DDTs possibly from the wide use of dicofol with high impurity of DDT compounds in this region. PMID- 22098497 TI - Expression profile of genes involved in pathogenesis of pediatric Crohn's disease. AB - BACKGROUND AND AIM: Expression profiling of genes specific to pediatric Crohn's Disease (CD) patients was performed to elucidate the molecular mechanisms underlying disease cause and pathogenesis at disease onset. METHODS: We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age- and sex matched controls without inflammatory bowel disease (IBD). RESULTS: Sequence analysis of 1000 clones enriched by SSH identified 75 functionally annotated human genes, represented by 430 clones. The 75 genes have potential involvement in gene networks, such as antigen presentation, inflammation, infection mechanism, connective tissue development, cell cycle and cancer. Twenty-eight genes were previously described in association with CD, while 47 were new genes not previously reported in the context of IBD. Additionally, 29 of the 75 genes have been previously implicated in bacterial and viral infections. Quantitative real-time reverse transcription polymerase chain reaction performed on ileal derived RNA from 13 CD and nine non-IBD patients confirmed the upregulation of extracellular matrix gene MMP2 (P = 0.001), and cell proliferation gene REG1A (P = 0.063) in our pediatric CD cohort. CONCLUSION: The retrieval of 28 genes previously reported in association with adult CD emphasizes the importance of these genes in the pediatric setting. The observed upregulation of REG1A and MMP2, and their known impact on cell proliferation and extracellular matrix remodeling, agrees with the clinical behavior of the disease. Moreover, the expressions of bacterial- and virus-related genes in our CD-patient tissues support the concept that microbial agents are important in the etiopathogenesis of CD. PMID- 22098501 TI - Evidence of nanocrystalline semiconducting graphene monoxide during thermal reduction of graphene oxide in vacuum. AB - As silicon-based electronics are reaching the nanosize limits of the semiconductor roadmap, carbon-based nanoelectronics has become a rapidly growing field, with great interest in tuning the properties of carbon-based materials. Chemical functionalization is a proposed route, but syntheses of graphene oxide (G-O) produce disordered, nonstoichiometric materials with poor electronic properties. We report synthesis of an ordered, stoichiometric, solid-state carbon oxide that has never been observed in nature and coexists with graphene. Formation of this material, graphene monoxide (GMO), is achieved by annealing multilayered G-O. Our results indicate that the resulting thermally reduced G-O (TRG-O) consists of a two-dimensional nanocrystalline phase segregation: unoxidized graphitic regions are separated from highly oxidized regions of GMO. GMO has a quasi-hexagonal unit cell, an unusually high 1:1 O:C ratio, and a calculated direct band gap of ~0.9 eV. PMID- 22098502 TI - Development of a duplex real-time PCR for the detection of Rickettsia spp. and typhus group rickettsia in clinical samples. AB - Molecular diagnosis using real-time polymerase chain reaction (PCR) may allow earlier diagnosis of rickettsiosis. We developed a duplex real-time PCR that amplifies (1) DNA of any rickettsial species and (2) DNA of both typhus group rickettsia, that is, Rickettsia prowazekii and Rickettsia typhi. Primers and probes were selected to amplify a segment of the 16S rRNA gene of Rickettsia spp. for the pan-rickettsial PCR and the citrate synthase gene (gltA) for the typhus group rickettsia PCR. Analytical sensitivity was 10 copies of control plasmid DNA per reaction. No cross-amplification was observed when testing human DNA and 22 pathogens or skin commensals. Real-time PCR was applied to 16 clinical samples. Rickettsial DNA was detected in the skin biopsies of three patients. In one patient with severe murine typhus, the typhus group PCR was positive in a skin biopsy from a petechial lesion and seroconversion was later documented. The two other patients with negative typhus group PCR suffered from Mediterranean and African spotted fever, respectively; in both cases, skin biopsy was performed on the eschar. Our duplex real-time PCR showed a good analytical sensitivity and specificity, allowing early diagnosis of rickettsiosis among three patients, and recognition of typhus in one of them. PMID- 22098504 TI - Palladium-catalyzed Heck-type reactions of alkyl iodides. AB - A palladium-catalyzed Heck-type reaction of unactivated alkyl iodides is described. This process displays broad substrate scope with respect to both alkene and alkyl iodide components and provides efficient access to a variety of cyclic products. The reaction is proposed to proceed via a hybrid organometallic radical mechanism, facilitating the Heck-type process with alkyl halide coupling partners. Initial intermolecular studies are also reported, demonstrating the potentially wide applicability of this approach in synthesis. PMID- 22098503 TI - Ablation of connexin30 in transgenic mice alters expression patterns of connexin26 and connexin32 in glial cells and leptomeninges. AB - Expression of connexin26 (Cx26), Cx30 and Cx43 in astrocytes and expression of Cx29, Cx32 and Cx47 in oligodendrocytes of adult rodent brain has been well documented, as has the interdependence of connexin expression patterns of macroglial cells in Cx32- and Cx47-knockout mice. To investigate this interdependence further, we examined immunofluorescence labelling of glial connexins in transgenic Cx30 null mice. Ablation of astrocytic Cx30, confirmed by the absence of immunolabelling for this connexin in all brain regions, resulted in the loss of its coupling partner Cx32 on the oligodendrocyte side of astrocyte oligodendrocyte (A/O) gap junctions, but had no effect on the localization of astrocytic Cx43 and oligodendrocytic Cx47 at these junctions or on the distribution of Cx32 along myelinated fibres. Surprisingly, gene deletion of Cx30 led to the near total elimination of immunofluorescence labelling for Cx26 in all leptomeningeal tissues covering brain surfaces as well as in astrocytes of brain parenchyma. Moreover northern blot analysis revealed downregulation of Cx26 mRNA in Cx30-knockout brains. Our results support earlier observations on the interdependency of Cx30/Cx32 targeting to A/O gap junctions and further suggest that Cx26 mRNA expression is affected by Cx30 gene expression. In addition, Cx30 protein may be required for co-stabilization of gap junctions or for co trafficking in cells. PMID- 22098505 TI - Simultaneous determination of seven bioactive components in Oolong tea Camellia sinensis: quality control by chemical composition and HPLC fingerprints. AB - A simple and reliable method of high-performance liquid chromatography (HPLC) was developed for the quality control of oolong tea (the dry leaves of Camellia sinensis ): the quality control included the HPLC fingerprint and the quantitative determination of seven bioactive compounds chemicals, namely, (-) gallocatechin, (-)-epigallocatechin, (-)-epigallocatechin gallate, caffeine, (-) epicatechin, gallocatechin gallate, and (-)-epicatechin gallate. The developed analyses of the chemicals excelled in quantifying the chemicals in oolong tea. The chemical fingerprint of oolong tea was established using the raw materials of three main production sites in China, that is, Fujian (southern and northern parts), Taiwan, and Guangdong. The fingerprints from different cultivated sources were analyzed by hierarchical cluster analysis, similarity analysis, principal component analysis (PCA), analysis of variance (ANOVA), and discriminant analysis. The results indicated that the combination of chromatographic fingerprint and quantification analysEs could be used for the quality assessment of oolong tea and its derived products. PMID- 22098506 TI - Giant tubular adenoma of the breast: a rare entity. PMID- 22098507 TI - Implications of the Frequent Hemodialysis Network-Daily Trial. AB - Despite many years of experience with hemodialysis, the outcomes of maintenance dialysis patients remain poor. The Frequent Hemodialysis Network-Daily (FHN Daily) Trial found that six times per week in-center short hemodialysis decreased left ventricular mass and improved self-reported physical functioning over a 1 year intervention period compared with conventional thrice-weekly dialysis. Despite the promising results, caution is needed in the projection of these intermediate outcomes to hard clinical endpoints, such as cardiovascular events and death. PMID- 22098508 TI - Operative innovations for colorectal cancer. PMID- 22098509 TI - Sealed Orifice Laparoscopic or Endoscopic (SOLE) Surgery: technology and technique convergence for next-step colorectal surgery. AB - The new avenue of minimally invasive surgery, referred to as single incision/access laparoscopy, is often presented as an alternative to standard multiport approaches, whereas in fact it is more usefully perceived as a complementary modality. The emergence of the technique can be of greater use both to patients and to the colorectal specialty if its principles can be merged into next-stage evolution by synergy with more conventional practice. In particular, rather than device specificity, what is needed is convergence of capability that can be applied by the same surgeon in differing scenarios depending on the individualized patient and disease characteristics. We detail here the global applicability of a simple access device construct that allows the provision of simple and complex single-port laparoscopy as well as contributing to multiport laparoscopic and transanal resections in a manner that is reliable, reproducible, ergonomical and economical. PMID- 22098510 TI - Optimizing patient outcomes in laparoscopic surgery. AB - There is increasing recognition that the entire peri-operative care delivered plays a vital role in determining patient's outcome. Optimisation of this care helps to prevent complications beyond immediate morbidity and mortality. Of the 20 factors described in Enhanced Recovery Programmes, some have a greater impact than others, with analgesia and fluid therapy being two of the main factors. 1 Analgesia - The main analgesic regimes used so far for laparoscopic colorectal surgery have been continuous thoracic epidural and patient controlled analgesia. There is a growing body of opinion that epidural analgesia may not be required for laparoscopic surgery. 2 Individualised goal directed therapy - It is now recognized that measuring flow rather than pressure within the cardiovascular system is more important. Fluid therapy impacts on the outcome by minimizing fluid shifts, optimizing stroke volume and restricting the salt load given whilst maintaining normovolaemia. Analgesia and fluid therapy, together with the remaining enhanced recovery criteria have led to the development of the trimodal approach. PMID- 22098511 TI - Near-infrared laparoscopy for real-time intra-operative arterial and lymphatic perfusion imaging. AB - Multimodal laparoscopic imaging systems possessing the capability for extended spectrum irradiation and visualization within a unified camera system are now available to provide enhanced intracorporeal operative anatomic and dynamic perfusion assessment and potentially augmented patient outcome. While ultraviolet range energies have limited penetration and hence are probably more useful for endoscopic mucosal interrogation, the near-infrared (NIR) spectrum is of greater potential utility for the purposes of examining inducible fluorescence in abdominopelvic tissue that can be achieved by administration of specific tracer agents, either directly into the circulation (e.g. for anastomotic perfusion assessment at the time of stapling) or into the lymphatic system (e.g. for lymph basin road-mapping and/or focussed target nodal assessment). This technology is also capable of supplementing anatomic recognition of the biliary system while implantable fibres can also be inserted intraoperatively for the purpose of safeguarding vital structures such as the oesphagus and ureters especially in difficult reoperations. It is likely that this technological capability will find a clear and common indication in colorectal specialist and general surgical departments worldwide in the near future. PMID- 22098512 TI - Early, minimally invasive closure of anastomotic leaks: a new concept. AB - Chronic pelvic sepsis after ileoanal or coloanal anastomosis precludes ileostomy closure and, even if closure is ultimately possible, function of the neorectum is badly affected. Early closure of the anastomotic leak might prevent chronic pelvic sepsis and its adverse sequelae. In our experience of early closure in a consecutive group of six patients with a leaking low anastomosis (five with ileoanal pouch anastomosis and one after a low anterior resection), we were able to achieve anastomotic closure in five by means of initial endosponge therapy followed either by early suture (four patients) or endoscopic clip repair (one patient). Early minimally invasive closure of low anastomotic leaks is therefore possible provided that the para-anastomotic cavity is drained well prior to closure and the anastomosis is defunctioned. PMID- 22098513 TI - Transanal extraction of the specimen during laparoscopic colectomy. AB - AIM: To assess the current state of the art of transanal specimen extraction in colonic resections. METHOD: A systematic literature search was conducted including the terms 'transrectal or transanal specimen extraction', 'Natural Orifice Specimen Extraction' and 'laparoscopic colectomy' for the period from 1955 to May 2011. Exclusion criteria were abdomino-perineal resections, pull through technique, experimental studies and paediatric population. RESULTS: Nineteen studies met the inclusion criteria, representing 154 patients. The overall postoperative complication rate was 10%. The risks of peritoneal contamination and sphincter dysfunction were evaluated by a single study of each. CONCLUSION: Transanal extraction is a feasible option to minimize incisions in colorectal surgery. PMID- 22098514 TI - Laparoscopic low anterior resection and transanal pull-through for low rectal cancer: a Natural Orifice Specimen Extraction (NOSE) technique. AB - Ultralow anterior resection with coloanal anastomosis has been proven to be oncologically sound and the majority of patients will have acceptable functional outcome. Here we describe a technique that combines laparoscopic ultralow total mesorectal excision with an intersphincteric dissection in order to allow the mobilized rectum and descending colon to be extracted via the muscular anal canal and so avoid any further abdominal incision other than laparoscopic port sites. We believe this novel approach to have significant clinical potential in selected patients. PMID- 22098515 TI - Extending the role of Transanal Endoscopic Microsurgery (TEM) in rectal cancer. AB - Increasingly it is becoming clear that there is a role for local excision of early rectal cancer by Transanal Endoscopic Microsurgery (TEM) as part of an organ-preservation strategy. This role is based on careful preoperative assessment, thorough postoperative histopathological examination and standardized follow up, with recourse to completion or salvage radical surgery in the face of poor prognostic factors, or early concerns over recurrent disease. Additionally, TEM is also proposed in selected circumstances after neoadjuvant treatment for rectal cancer. This latter topic is even more controversial with clinical evidence still evolving, but specialist centres report impressive results that cannot be ignored in the modern management of rectal cancer. PMID- 22098516 TI - Can mesorectal lymph node excision be avoided in rectal cancer surgery? AB - Rectal excision is the standard in rectal cancer treatment. The morbidity of rectal excision, together with the low rate of positive lymph nodes in patients with a good response after radiochemotherapy, raises the challenging concept of organ preservation. Patients with a complete response can benefit from a nonoperative strategy based on a strict follow up. Those with a complete or subcomplete response can be treated by local excision. Limitations in accurately assessing a complete response by conventional and modern imaging modalities suggest that local excision is more appropriate for the majority of patients when organ preservation is being considered. The encouraging results of retrospective series of local excision in downstaged clinical T2/T3 low rectal cancer after radiochemotherapy, however, need to be confirmed by the ongoing multicentre phase II United States and phase III French trials before routinely proposing organ preservation in patients with a good response. PMID- 22098517 TI - Totally transrectal endoscopic total mesorectal excision (TME). AB - Surgical treatment has been in constant evolution in the search for minimizing incisions regardless of the complexity of the operation. Natural Orifice Translumenal Endoscopic Surgery (NOTES) represents this progression of surgery to less invasive procedures. Transanal endoscopic microsurgery (TEM) is an ideal NOTES platform to access the peritoneal cavity endoscopically through the anus and specifically to allow colorectal resections be performed through smaller, or indeed without, abdominal incisions. Transanal rectosigmoidectomy with total mesorectal excision (TME) using TEM is a feasible and oncologically safe option. Such use of currently available combined hybrid laparoendoscopic systems provides a safe platform to define future clinical applications and advantages of NOTES. Furthermore, it stimulates the active development of technologies that will support and enable it. PMID- 22098518 TI - Natural orifice transluminal endoscopic surgery (NOTES) and colorectal cancer? AB - Surgical techniques and technologies are rapidly evolving. In the field of colorectal surgery the transanal video-assisted approach was introduced by Buess, 30 years ago, with transanal endoscopic microsurgery (TEM). In more recent years different techniques and technologies have been proposed, including natural orifice specimen extraction (NOSE), natural orifice transluminal endoscopic surgery (NOTES) and single-access surgery. Furthermore, a better understanding of the prognostic and risk factors of rectal cancer has allowed TEM to expand its indications to local resection of selected tumours, and more recently there have been proposals for sentinel node biopsy in colon and rectal cancer. PMID- 22098519 TI - Transrectal natural orifice translumenal endoscopic surgery (NOTES) for colorectal resection. AB - Natural orifice translumenal endoscopic surgery (NOTES) is a new surgical paradigm involving performance of intra-abdominal surgery via a natural orifice and thereafter peritoneal access through an intentionally created hole in a hollow viscus. The vast majority of research in this rapidly evolving field had involved access via an oral or vaginal route. Access via a transanal route, other than the obvious concern over contamination, has many appealing attributes. In addition, transanal surgery has long been a common procedure lending a valuable clinical experience to the foundation of this field of research. Examples of preclinical and clinical research on transanal NOTES colorectal resections are here presented and discussed. PMID- 22098520 TI - Safe sigmoid access for natural orifice transluminal endoscopic surgery (NOTES). AB - One of the main challenges in transluminal surgery is sterile and safe access. For many interventions, a transanal approach would be ideal but it is considered too risky because of contamination and the danger of secondary leakage. A new safe and sterile transanal access was developed, combining four basic principles: (i) the creation of a decontaminating hydroperitoneum, (ii) the use of an overtube, (iii) defining the entry point with ultrasound and (iv) dedicated closure technique. Applicability and reliability was first proven in extensive animal experiments. Feasibility of the concept in humans was subsequently demonstrated in cadavers. PMID- 22098521 TI - Individualization of surgical management for early-stage colonic cancer. AB - A significant number of patients each year undergo radical segmental colectomy for node-negative colonic cancer in the UK. They are likely to represent 50% of our colonic cancer population in the future due to the implementation of the National Bowel Cancer Screening Programme. Short-term morbidity rates of up to 40% are associated with the current surgical treatment and need serious consideration. In this article, we discuss a combination of two techniques that will allow minimally invasive treatment in an increasing number of patients with early colonic cancer. PMID- 22098522 TI - Current clinical status of sentinel lymph nodes in colon and proximal rectal cancer. AB - The postoperative report of the lymph node status of colorectal cancer in clinical practice is not a given fact. Among other factors, it is dependent on the experience and technique of the surgeon as well as the pathologist. Therefore a method like sentinel lymph node biopsy (SLNB) that identifies and provides for analysis the lymph node at highest risk for tumour involvement would be highly beneficial. Unlike in breast cancer or melanoma, SLNB is more difficult to apply in colorectal cancer and is still not ready for clinical routine application for these tumor entities. However, careful patient selection and expertise of the involved specialists can improve the quality and results of SLNB in colorectal cancer. Especially in the early stage cancer patients, SLNB may be helpful to identify the earliest signs of lymphatic dissemination (thereby upstaging the patient) or to encourage a limited extent of resection. PMID- 22098523 TI - Laparoscopic lymphatic roadmapping with blue dye and radioisotope in colon cancer. AB - Lymphatic mapping (LM) and sentinel lymph node (SLN) identification by blue dye in colon cancer is a procedure feasible during minimally invasive surgery, with good specificity, but still a low sensitivity (78% in our series). These results are in accordance with the literature and have limited more widespread diffusion of the method, both as a tool for upstaging and more controversially, as a potential roadmap to a tailored lymphadenectomy. It is possible to improve the results of LM with careful selection of patients and by the use of an intraoperative gamma camera. The preliminary results of intra-operative lymphoscintigraphy are promising in a well-selected small group of patients, with high levels of sensitivity and specificity. If these results are confirmed in further prospective analyses, it may be possible to undertake selected, tailored lymphadenectomy. PMID- 22098524 TI - Near infrared fluorescence lymphatic laparoscopy of the colon and mesocolon. AB - During surgery, a surgeon relies on the vision of his eyes and the touch of his hands. While laparoscopic surgery for colon cancer has proven to be safe and effective, it still remains a technically difficult procedure. Although it is associated with reduced haptic feedback, by enforcing the power of visual guidance, the loss of this feedback can be (partly) compensated for. Here we describe how the use of near-infrared dyes and fluorescence laparoscopy could help improve tumour staging and therefore lead to better selection of patients for postoperative adjuvant chemotherapy. More controversially, and analogous to melanoma and breast cancer surgery with sentinel node biopsy, we speculate that local resection with SLN harvesting in early colon cancer might change the therapeutic and surgical strategy in colon cancer. PMID- 22098525 TI - Extended resections for colorectal cancer - indications for supraradical lymphadenectomy. AB - The laparoscopic approach to standard resections in colorectal cancer has proven that it may provide equal rates of R0 resections and adequate retrieval of lymph nodes as open procedures if performed by experienced hands. There might be difficulties in more advanced tumors or those with lymphatic spread beyond typical drainage areas and more extensive operations might be required. An atypical pattern of lymphatic spread often is associated with other adverse factors such as multifocality of primary cancers and adverse tumorbiological factors such as grade. Such patient subgroups may be defined beforehand and include particularly patients with underlying ulcerative colitis. Repetitively, extended lymph node dissection approaches have been advocated, however neither in randomised trails nor in meta-analysis has a more favourable outcome of patients undergoing such extended lymphatic dissections been demonstrated. Sticking to the rules of classical dissection of lymphatic drainage basins with removal of adequate lymph node numbers is one corner stone for successful treatment of colorectal cancer. The other one refers to a detailed description of the procedure performed in order to make the surgical procedure trackable. PMID- 22098526 TI - Robotic platforms for general and colorectal surgery. AB - Surgeons are increasingly turning to new technologies to help them overcome the barriers imposed by minimally invasive surgery (MIS). Robotics is an enabling technology with obvious applications to MIS. This manuscript looks at robotic platforms for general surgical application and explores the advantages, limitations and possible future roles. PMID- 22098527 TI - Multiplex ligation-dependent probe amplification (MLPA): a reliable alternative for fetal chromosome analysis? AB - OBJECTIVE: To determine whether molecular karyotyping using multiple ligation probe amplification (MLPA) is a reliable alternative for quick and accurate diagnosis of fetal chromosomal abnormalities. METHODS: MLPA, using specialised probe sets designed to detect aneuploidy, major chromosomal rearrangements and recognised microdeletion syndromes, was used to analyse chorionic villi or amniocytes left after traditional karyotyping of 476 fetuses for clinical indications. RESULTS: An abnormal result was obtained in 190 cases, including 124 trisomies, 21 sex chromosome anomalies, 14 triploidies, and 31 rearrangements or mosaics. All trisomies were detected by all three techniques, but triploidies were only detected by karyotyping and QF-PCR. In 19 of the 31 cases of rearrangements or mosaicism there was an uncertain or high risk of adverse outcome. Traditional karyotyping detected 13 of the 19 pathogenic rearrangements, MLPA detected 18, and QF-PCR did not detect any. CONCLUSION: MLPA, using specialized probe sets, detects more chromosomal rearrangements, conferring significant risk of adverse outcome than karyotyping. A combination of qfPCR and MLPA could be a good, rapid alternative to current practice. In the future, used in conjunction with non-invasive prenatal diagnosis based on cell free fetal DNA it might provide a rapid and efficient approach to fetal karyotyping. PMID- 22098528 TI - Quantification of the adverse effect of ethinylestradiol containing oral contraceptive pills when used in conjunction with growth hormone replacement in routine practice. AB - OBJECTIVE: Oestrogen antagonizes the action of growth hormone (GH). For women with combined GH and oestrogen deficiency, transdermal oestradiol is more favourable in this regard compared to oral oestradiol. Oral contraceptive pills containing ethinylestradiol (EE) are commonly used in young women with GHD and there is little information on the impact of this form of oestrogen. DESIGN: A case note review of women with growth hormone deficiency (GHD) attending a tertiary endocrine clinic comparing the dose of GH and serum insulin-like growth factor 1 concentrations and the type of exogenous oestrogen. METHODS: All women with GHD between the ages of 18 and 47 attending University College London Hospitals (UCLH) were included and grouped according to type of oestrogen replacement. Weight, GH dose and serum IGF-I concentrations were recorded at 121 visits in 88 women. RESULTS: The daily dose of GH was significantly higher and the GH responsivity was significantly lower in the EE group compared to those taking no oestrogen and transdermal oestrogen. The additional cost of GH for women using EE compared to transdermal oestradiol was L6016 per patient per year. Effectiveness of GH improved in all women changing from EE to another form of oestrogen. CONCLUSION: Use of oral contraceptive pills containing EE should be avoided in women receiving treatment with GH. Alternative options include oral or transdermal hormone replacement therapy (HRT) preparations for those that require oestrogen replacement or a progesterone-based regimen for contraceptive purposes. PMID- 22098529 TI - Ultrasensitive Pb(II) potentiometric sensor based on copolyaniline nanoparticles in a plasticizer-free membrane with a long lifetime. AB - A newly designed Pb(II) potentiometric sensor based on intrinsically conducting nanoparticles of solid poly(aniline-co-2-hydroxy-5-sulfonic aniline) possessing many ligating functional groups like -NH-, -N=, -OH, -SO(3)H, -NH(2) as ionophores in plasticizer-free vinyl resin solid membranes has been fabricated. A linear Nernstian response is obtained within a wide Pb(II) activity range from 1.0 * 10(-3) to 1.0 * 10(-10) M with a detection limit as low as 2.2 * 10(-11) M. The pH independent plateau ranges between 3.5 and 7.0. After 15 months' usage, the sensor maintains 95% performance parameters. Its anti-interference ability to Cu(II), Cd(II), Ag(I), and Hg(II) is much stronger than other sensors with a detection limit at (sub)nanomolar level. Electrochemical impedance spectroscopy reveals that the solid sensing membrane has a diffusion coefficient of around 5 * 10(-14) to 1 * 10(-13) cm(2) s(-1). The much lower diffusion coefficient for Pb(II) is highly beneficial for the elimination of Pb(II) flux across the membrane. The wide detection concentration range, low detection limit, high selectivity, extensive pH window, and long lifetime make for a robust sensor giving reliable measurement of Pb(II) content with potential application in real world samples at trace levels. PMID- 22098530 TI - Versatile behavior of the fluorophosphinidene ligand in iron carbonyl chemistry. AB - Fluorophosphinidene (PF) is a versatile ligand found experimentally in the transient species M(CO)(5)(PF) (M = Cr, Mo) as well as the stable cluster Ru(5)(CO)(15)(MU(4)-PF). The PF ligand can function as either a bent two-electron donor or a linear four-electron donor with the former being more common. The mononuclear tetracarbonyl Fe(PF)(CO)(4) is predicted to have a trigonal bipyramidal structure analogous to Fe(CO)(5) but with a bent PF ligand replacing one of the equatorial CO groups. The tricarbonyl Fe(PF)(CO)(3) is predicted to have two low-energy singlet structures, namely, one with a bent PF ligand and a 16-electron iron configuration and the other with a linear PF ligand and the favored 18-electron iron configuration. Low-energy structures of the dicarbonyl Fe(PF)(CO)(2) have bent PF ligands and triplet spin multiplicities. The lowest energy structures of the binuclear Fe(2)(PF)(CO)(8) and Fe(2)(PF)(2)(CO)(7) derivatives are triply bridged structures analogous to the experimental structure of the analogous Fe(2)(CO)(9). The three bridges in each Fe(2)(PF)(CO)(8) and Fe(2)(PF)(2)(CO)(7) structure include all of the PF ligands. Other types of low energy Fe(2)(PF)(2)(CO)(7) structures include the phosphorus-bridging carbonyl structure (FP)(2)COFe(2)(CO)(6), lying only ~2 kcal/mol above the global minimum, as well as an Fe(2)(CO)(7)(MU-P(2)F(2)) structure in which the two PF groups have coupled to form a difluorodiphosphene ligand unsymmetrically bridging the central Fe(2) unit. PMID- 22098531 TI - Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4. AB - Ichthyosis is a heterogeneous disorder characterized by abnormal skin scaling over the whole body. Autosomal recessive congenital ichthyosis (ARCI) comprises various forms, the most important of which are lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). Seven genes have been identified to be causative of ARCI, and these account for disease in 60-80% of the patients. There is notable phenotypic overlap between the major forms of ARCI, and a strong genotype-phenotype correlation has not been found. Here, we initially aimed to identify the causative gene in a large Iranian ARCI pedigree, and subsequently performed genetic analysis on four other affected pedigrees. A genotype-phenotype correlation was sought. Whole genome homozygosity mapping using high-density single nucleotide polymorphism chips was performed on the large pedigree. Linkage to chromosome 5 and a mutation in NIPAL4 causing p.G297R were identified. The same mutation was also identified in two of the remaining four Iranian pedigrees. Two of the NIPAL4 mutation bearing pedigrees were classified as CIE and one as LI. Notably, all NIPAL4 mutation-bearing patients manifested diffuse yellowish keratoderma on the palms and soles. We provide evidence suggesting presentation of this diffuse yellowish keratoderma may be indicative of mutations in NIPAL4, providing an easily assessable genotype-phenotype correlation. PMID- 22098532 TI - Lower limb joint kinetics and ankle joint stiffness in the sprint start push-off. AB - Sprint push-off technique is fundamental to sprint performance and joint stiffness has been identified as a performance-related variable during dynamic movements. However, joint stiffness for the push-off and its relationship with performance (times and velocities) has not been reported. The aim of this study was to quantify and explain lower limb net joint moments and mechanical powers, and ankle stiffness during the first stance phase of the push-off. One elite sprinter performed 10 maximal sprint starts. An automatic motion analysis system (CODA, 200 Hz) with synchronized force plates (Kistler, 1000 Hz) collected kinematic profiles at the hip, knee, and ankle and ground reaction forces, providing input for inverse dynamics analyses. The lower-limb joints predominately extended and revealed a proximal-to-distal sequential pattern of maximal extensor angular velocity and positive power production. Pearson correlations revealed relationships (P < 0.05) between ankle stiffness (5.93 +/- 0.75 N x m x deg(-1)) and selected performance variables. Relationships between negative power phase ankle stiffness and horizontal (r = -0.79) and vertical (r = 0.74) centre of mass velocities were opposite in direction to the positive power phase ankle stiffness (horizontal: r = 0.85; vertical: r = -0.54). Thus ankle stiffness may affect the goals of the sprint push-off in different ways, depending on the phase of stance considered. PMID- 22098533 TI - Comparative study of the in situ immune response in oral and nasal mucosal leishmaniasis. AB - Mucosal Leishmaniasis (ML) may occur in both nasal and oral mucosa. However, despite the impressive tissue destruction, little is known about the oral involvement. To compare some changes underlying inflammation in oral and nasal ML, we performed immunohistochemistry on mucosal tissue of 20 patients with ML (nasal [n = 12]; oral [n = 8] lesions) and 20 healthy donors using antibodies that recognize inflammatory markers (CD3, CD4, CD8, CD22, CD68, neutrophil elastase, CD1a, CLA, Ki67, Bcl-2, NOS2, CD62E, Fas and FasL). A significantly larger number of cells, mainly T cells and macrophages, were observed in lesions than in healthy tissue. In addition, high nitric oxide synthase 2 (NOS2) expression was associated with a reduced detection of parasites, highlighting the importance of NOS2 for parasite elimination. Oral lesions had higher numbers of neutrophils, parasites, proliferating cells and NOS2 than nasal lesions. These findings, together with the shorter duration of oral lesions and more intense symptoms, suggest a more recent inflammatory process. It could be explained by lesion-induced oral cavity changes that lead to eating difficulties and social stigma. In addition, the frequent poor tooth conservation and gingival inflammation tend to amplify tissue destruction and symptoms and may impair and confuse the correct diagnosis, thus delaying the onset of specific treatment. PMID- 22098534 TI - Partitioning the effects of an ecosystem engineer: kangaroo rats control community structure via multiple pathways. AB - 1. Ecosystem engineers impact communities by altering habitat conditions, but they can also have strong effects through consumptive, competitive and other non engineering pathways. 2. Engineering effects can lead to fundamentally different community dynamics than non-engineering effects, but the relative strengths of these interactions are seldom quantified. 3. We combined structural equation modelling and exclosure experiments to partition the effects of a keystone engineer, the giant kangaroo rat (Dipodomys ingens), on plants, invertebrates and vertebrates in a semi-arid California grassland. 4. We separated the effects of burrow creation from kangaroo rat density and found that kangaroo rats increased the diversity and abundance of other species via both engineering and non engineering pathways. 5. Engineering was the primary factor structuring plant and small mammal communities, whereas non-engineering effects structured invertebrate communities and increased lizard abundance. 6. These results highlight the importance of the non-engineering effects of ecosystem engineers and shed new light on the multiple pathways by which strong-interactors shape communities. PMID- 22098535 TI - Iron-catalyzed rearrangements and cycloaddition reactions of 2H-chromenes. AB - Iron(III) salts catalyze the tandem rearrangement/hetero-Diels-Alder reaction of 2H-chromenes to yield tetrahydrochromeno heterocycles. The process can occur as a homodimerization and cycloaddition process using electron-rich dienophiles. Deuterium labeling and mechanistic studies revealed a hydride shift and ortho quinone methide cycloaddition reaction pathway. PMID- 22098536 TI - Use of antiviral therapy in surveillance: impact on outcome of hepatitis B related hepatocellular carcinoma. AB - BACKGROUND: Antiviral therapy for hepatitis B virus (HBV) infection is frequently prescribed for patients with chronic HBV infection during surveillance for hepatocellular carcinoma (HCC). In patients who subsequently develop HCC, the impact of antiviral therapy on the outcome of HCC remains unclear. AIMS: We aimed to study the impact of antiviral therapy on the survival of patients who developed HCC. METHODS: From two prospective surveillance cohorts, the use of antiviral therapy for patients with HCC was retrospectively reviewed. We compared the overall survival, liver function and tumour characteristics between patients with and without antiviral therapy during surveillance. Multivariate analysis was conducted to determine the independent prognostication of antiviral therapy. RESULTS: During a median follow-up of 10.1 years of 1429 patients, 148 cases of HCC were diagnosed and followed up for a median of 5.7 years. Twenty-nine patients were given antiviral therapy during surveillance and continued treatment after diagnosis of HCC. The median survival of this group of patients was better than the rest of cohorts (hazard ratio: 0.472; 95% CI: 0.25-0.89; P = 0.0191). Use of antiviral therapy remained an independent prognostic factor after adjustment for demographic factors and tumour staging on multivariate analysis. Exploratory analysis revealed that patients who commenced antiviral therapy during surveillance had lower HBV DNA, lower serum alanine transaminase, better hepatic reserves and higher rate of local treatment at diagnosis of HCC. CONCLUSION: This study provides evidence that commencement of antiviral therapy during the surveillance period is associated with improvement in overall survival in HBV-related HCC. PMID- 22098537 TI - A possible involvement of p62/sequestosome-1 in the process of biliary epithelial autophagy and senescence in primary biliary cirrhosis. AB - BACKGROUND AND AIMS: Given autophagy is involved in the pathogenesis in primary biliary cirrhosis (PBC), we examined an involvement of p62 sequestosome-1 (p62), a specific cargo for autophagy, in the process of autophagy and cellular senescence in PBC. METHODS: We examined immunohistochemically the expression of p62 in livers taken from patients with PBC (n = 46) and control livers (n = 78) and its colocalization with microtubule-associated proteins-light chain 3beta (LC3), lysosome-associated membrane protein-1 (LAMP-1) and senescent markers (p16(INK) (4a) and p21(WAF) (1/Cip1) ). We examined the expression of p62 and LC3 in cultured biliary epithelial cells (BECs) treated with various stress. The effect of p62 knockdown with siRNA on stress-induced autophagy and cellular senescence was also assessed. RESULTS: The expression of p62 was specifically seen in cytoplasmic aggregates in BECs in the inflamed and damaged small bile ducts (SBDs) in PBC, when compared with non-inflamed ones in PBC and in control livers (P < 0.01). The co-expression of p62 with LC3, LAMP-1 and senescent markers was seen in the inflamed SBDs in PBC, but the intracytoplasmic localization was different. The expression of p62 and LC3 was significantly upregulated in BECs treated with various stress (P < 0.01) and pretreatment with bafilomycin A1 enhanced the accumulation of p62-positive aggregates in BECs with serum deprivation. The knockdown of p62 decreased stress-induced autophagy and cellular senescence. CONCLUSION: The aggregation of p62 is specifically increased in the damage bile ducts in PBC and may reflect dysfunctional autophagy, followed by cellular senescence in the pathogenesis of bile duct lesions in PBC. PMID- 22098538 TI - The utility of near infrared spectroscopy in detecting intracranial hemorrhage in children. AB - A prospective case-control study was conducted in a tertiary care pediatric intensive care unit (PICU) to evaluate the use of near infrared spectroscopy (NIRS) for the detection of intracranial hemorrhage (ICH) in children. Subjects 0 14 years of age who had a computed tomography (CT) scan of the head performed as part of clinical care were eligible for enrollment. The children were stratified into two groups based on whether the CT was normal or abnormal. Children in the abnormal imaging cohort were further divided into those with ICH and those with other abnormalities of the brain parenchyma (contusions, diffuse axonal injury [DAI], or cerebral edema) or fractures. NIRS measurements were performed on all subjects within 24 h of head CT. The NIRS operator was blinded to the presence or absence of ICH. NIRS measurements were performed in eight different scalp locations (four bilaterally). A total of 103 measurements were made. The optical density (OD) was automatically calculated by comparing the reflected and diffused optical signal. A DeltaOD>0.2 between hemispheres in any scalp location was considered abnormal. NIRS was performed in a total of 28 subjects: 7 had normal imaging and 21 had abnormal imaging. Of those with abnormal imaging, 12 had ICH. The sensitivity and specificity of NIRS at detecting ICH was 1.0 and 0.8, respectively. The positive and negative predictive values were 0.8 and 1.0, respectively. In conclusion, NIRS correctly identified all cases of ICH in this pilot study. Our preliminary results suggest that NIRS may be beneficial in the evaluation of a child with possible ICH. PMID- 22098539 TI - Indexed left atrial volume is superior to left atrial diameter in predicting nonvalvular atrial fibrillation recurrence after successful cardioversion: a prospective study. AB - BACKGROUND: Although indexed left atrial volume (iLAV) is the most accurate measure of left atrial size, it has not been evaluated prospectively as predictor of recurrence of atrial fibrillation (AFib) after successful cardioversion (CV). METHODS: We prospectively selected 76 patients (mean age 66.1 +/- 13.6 years, 65.8% men) with AFib who underwent successful CV. Baseline clinical and echocardiographic characteristics were obtained before CV. LAV was measured using Simpson's method and indexed to body surface area. All patients were scheduled for follow-up visit at 1, 6, 12 months, and then annually. A 24-hour Holter ECG was performed within 6 months and each time the patients reported symptoms suggestive of arrhythmia. RESULTS: The 52 patients (68.4%) with AFib recurrence had larger iLAV (35.5 +/- 8.9 mL/m(2) vs 27.0 +/- 6.7 mL/m(2) , P < 0.001). Anteroposterior LA diameter was not associated with AFib relapse (OR 1.08, 95% CI: 0.96-1.21, P = 0.09). Each unit increase in iLAV was associated with a 1.15 fold increased risk of recurrence (OR 1.15, 95% CI: 1.06-1.25, P < 0.001). In a multivariable model, iLAV remained the only independent predictor of relapse (adjusted OR 1.14, 95% CI: 1.02-1.28, P = 0.02). The area under ROC curves, generated to compare LA diameter, and iLAV as predictors of AFib recurrence were 0.56 (SE 0.07) versus 0.78 (SE 0.05), respectively (P = 0.003). CONCLUSION: This is the first prospective study to show that larger iLAV, as a more accurate measure of LA remodeling than anteroposterior diameter, is strongly and independently associated with a higher risk of AFib recurrence after CV. PMID- 22098540 TI - Effects of music intervention with nursing presence and recorded music on psycho physiological indices of cancer patient caregivers. AB - AIMS AND OBJECTIVES: To compare the effects of music intervention with nursing presence and recorded music on blood volume pulse amplitude, the low/high frequency ratio component of heart rate variability, depression, anxiety and sleep quality in cancer patient caregivers; to compare the participants evaluation of these two forms of musical intervention. BACKGROUND: Presence is one of the activities of caring. However, little is known about the effect of music intervention with nursing presence on psycho-physiological indices. DESIGN: Randomised crossover controlled trial. METHOD: Thirty-four female participants were randomly assigned to a music intervention with nursing presence/recorded music sequence or recorded music/music intervention with nursing presence sequence. Each intervention lasted 30 minutes and was held at the participant's home. The music intervention with nursing presence consisted of an erhu and recorder performance. In the recorded music session, participants listened to prerecorded music for 30 minutes. Continuous measurements of blood volume pulse and low/high frequency ratio were taken throughout the procedure. Depression, anxiety and sleep quality were measured before and after each intervention. RESULTS: Both music intervention with nursing presence and recorded music interventions had beneficial effects on anxiety, depression and blood volume pulse amplitude. Significant differences between the two interventions were also observed for anxiety. Music intervention with nursing presence was more effective in lessening anxiety and on improving the ease of getting to sleep compared with recorded music (p < 0.05). All participants reported that they preferred music intervention with nursing presence to recorded music. Significant differences were found in music evaluation scores between the two interventions in terms of harmony and friendliness (p < 0.05). CONCLUSIONS: Both music interventions were beneficial, as measured on psycho-physiological indices. The music intervention with nursing presence provided a more friendly music experience to the listeners. RELEVANCE TO CLINICAL PRACTICE: The findings provide evidence for nurses that the therapeutic use of music and nursing presence as a research-based nursing intervention for the welfare of caregivers. PMID- 22098541 TI - RD-CODOX-M/IVAC with rituximab and intrathecal liposomal cytarabine in adult Burkitt lymphoma and 'unclassifiable' highly aggressive B-cell lymphoma. AB - Specific trials on adult Burkitt lymphoma (BL) and 'unclassifiable' lymphomas with features intermediate between BL and diffuse large B-cell lymphoma (BL/DLBCL) are advocated which include substantial numbers of older patients, to improve treatment feasibility, while countering risks of systemic and central nervous system (CNS) recurrences. We prospectively evaluated a modified CODOX M/IVAC (CODOX-M: cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate; IVAC: ifosfamide, etoposide and high-dose cytarabine) regimen by the addition of rituximab (R) and liposome-encapsulated cytarabine (D) to increase antitumour activity and halve the number of intrathecal treatments. Thirty adults (40% >60years) with BL (n=15) and BL/DLBCL (n=15) were accrued. Primary endpoints were progression-free survival (PFS), CNS recurrence, and liposomal cytarabine-associated toxicity. Eighty percent of patients received the whole treatment programme, the remaining cases received at least three full courses. Application of the RD-CODOX-M/IVAC regimen resulted in remarkable 4-year PFS (78%) and complete remission (CR) rates (93%). However, PFS was significantly lower in patients older than 60years as compared to younger ones (49%vs 93%, P=0.03; median, 36months), despite high actual dose-intensity, CR rate and tolerability. Reduced-intensity intratechal prophylaxis through liposomal cytarabine was effective because the CNS failure rate was low (3.4%) and without severe neurological toxicities. The RD-CODOX-M/IVAC strategy is feasible and highly effective, but improving outcomes in elderly patients remains a priority. PMID- 22098542 TI - Osthole enhances glucose uptake through activation of AMP-activated protein kinase in skeletal muscle cells. AB - AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. Activation of AMPK in skeletal muscles, the liver, and adipose tissues results in a favorable metabolic milieu for preventing and treating type 2 diabetes, i.e., decreased levels of circulating glucose, plasma lipids, and ectopic fat accumulation and enhanced insulin sensitivity. Osthole was extracted from a Chinese herbal medicine, and we found that it had glucose lowering activity in our previous study. However, the detailed glucose lowering mechanisms of osthole are still unclear. In this study, we used skeletal muscle cells to examine the underlying molecular mechanisms of osthole's glucose lowering activity. A Western blot analysis revealed that osthole significantly induced phosphorylation of AMPK and acetyl-CoA carboxylase (ACC). Next, we found that osthole significantly increased the level of translocation of glucose transporter 4 (GLUT4) to plasma membranes and glucose uptake in a dose-dependent manner. Osthole-induced glucose uptake was reversed by treatment with Compound C, an AMPK inhibitor, suggesting that osthole-induced glucose uptake was mediated in an AMPK dependent manner. The increase in the AMP:ATP ratio was involved in osthole's activation of AMPK. Finally, we found that osthole counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that the increase in the AMP:ATP ratio by osthole triggered activation of the AMPK signaling pathway and led to increases in plasma membrane GLUT4 content and glucose uptake level. Therefore, osthole might have potential as an antidiabetic agent for treating diabetes. PMID- 22098543 TI - Myelin imaging compound (MIC) enhanced magnetic resonance imaging of myelination. AB - The vertebrate nervous system is characterized by myelination, a fundamental biological process that protects the axons and facilitates electric pulse transduction. Damage to myelin is considered a major effect of autoimmune diseases such as multiple sclerosis (MS). Currently, therapeutic interventions are focused on protecting myelin integrity and promoting myelin repair. These efforts need to be accompanied by an effective imaging tool that correlates the disease progression with the extent of myelination. To date, magnetic resonance imaging (MRI) is the primary imaging technique to detect brain lesions in MS. However, conventional MRI cannot differentiate demyelinated lesions from other inflammatory lesions and therefore cannot predict disease progression in MS. To address this problem, we have prepared a Gd-based contrast agent, termed MIC (myelin imaging compound), which binds to myelin with high specificity. In this work, we demonstrate that MIC exhibits a high kinetic stability toward transmetalation with promising relaxometric properties. MIC was used for in vivo imaging of myelination following intracerebroventricular infusion in the rat brain. MIC was found to distribute preferentially in highly myelinated regions and was able to detect regions of focally induced demyelination. PMID- 22098548 TI - Plasminogen activator inhibitor 1 RNAi suppresses gastric cancer metastasis in vivo. AB - Cancer metastasis remains the primary cause of pain, suffering, and death in cancer patients, and even the most current therapeutic strategies have not been highly successful in preventing or inhibiting metastasis. In most patients with scirrhous gastric cancer (one of the most aggressive of diffuse-type gastric cancer), recurrence occurs even after potentially curative resection, most frequently in the form of peritoneal metastasis. Given that the occurrence of diffuse-type gastric cancers has been increasing, the development of new strategies to combat metastasis of this disease is critically important. Plasminogen activator inhibitor-1 (PAI-1) is a critical factor in cancer progression; thus, PAI-1 RNAi may be an effective therapy against cancer metastasis. In the present study, we used an RNAi technique to reduce PAI-1 expression in an in vivo model system for gastric cancer metastasis. Ex vivo plasmid transfection and adenovirus infection were tested as mechanisms to incorporate specific PAI-1 RNAi vectors into human gastric carcinoma cells. Both approaches significantly decreased peritoneal tumor growth and the formation of bloody ascites in the mouse model, suggesting that this approach may provide a new, effective strategy for inhibiting cancer metastasis. PMID- 22098549 TI - Filariasis presenting as gynecomastia. PMID- 22098550 TI - Liver disease in Viet Nam: screening, surveillance, management and education: a 5 year plan and call to action. AB - Despite a high prevalence of liver disease in Viet Nam, there has been no nationwide approach to the disease and no systematic screening of at-risk individuals. Risk factors include chronic hepatitis B (estimated prevalence of 12%), chronic hepatitis C (at least 2% prevalence), and heavy consumption of alcohol among men. This combination of factors has resulted in liver cancer being the most common cause of cancer death in Viet Nam. There is a general lack of understanding by both the general public and health-care providers about the major risk to health that liver disease represents. We report here the initial steps taken as part of a comprehensive approach to liver disease that will ultimately include nationwide education for health-care providers, health educators, and the public; expansion of nationwide screening for hepatitis B and C followed by hepatitis B virus vaccination or treatment of chronic hepatitis B and/or hepatitis C; education about alcoholic liver disease; long-term surveillance for liver cancer; reduction of infection transmission related to medical, commercial, and personal re-use of contaminated needles, syringes, sharp instruments, razors, and inadequately sterilized medical equipment; and ongoing collection and analysis of data about the prevalence of all forms of liver disease and the results of the expanded screening, vaccination, and treatment programs. We report the beginning results of our pilot hepatitis B screening program. We believe that this comprehensive nationwide approach could substantially reduce the morbidity and mortality from liver disease and greatly lessen the burden in terms of both lives lost and health-care costs. PMID- 22098551 TI - Characterization of Bordetella holmesii isolates from patients with pertussis like illness in The Netherlands. AB - Bordetella holmesii is a recently described human pathogen mainly isolated from blood. However, in the US and Canada, B. holmesii has also been cultured from the nasopharynx of patients with pertussis-like symptoms. To the best of our knowledge, respiratory isolates from Europe have not been characterized. Here, we report the isolation and characterization of B. holmesii from Dutch patients with pertussis-like illness. Species determination was confirmed by 16S rRNA gene sequencing and detection by PCR of IS481 and bhoE, a gene not found in Bordetella pertussis but present in B. holmesii. Comparative genomic hybridization (CGH) with microarrays revealed that the Dutch isolates formed a cluster distinct from isolates from the US and UK suggesting a distinct population or an epidemiological relationship between the Dutch isolates. All isolates contained a locus involved in iron uptake, previously suggested to originate from B. pertussis. The causes for the apparent increase in the isolation of B. holmesii are discussed. PMID- 22098552 TI - Photon-regulated DNA-enzymatic nanostructures by molecular assembly. AB - Future smart nanostructures will have to rely on molecular assembly for unique or advanced desired functions. For example, the evolved ribosome in nature is one example of functional self-assembly of nucleic acids and proteins employed in nature to perform specific tasks. Artificial self-assembled nanodevices have also been developed to mimic key biofunctions, and various nucleic acid- and protein based functional nanoassemblies have been reported. However, functionally regulating these nanostructures is still a major challenge. Here we report a general approach to fine-tune the catalytic function of DNA-enzymatic nanosized assemblies by taking advantage of the trans-cis isomerization of azobenzene molecules. To the best of our knowledge, this is the first study to precisely modulate the structures and functions of an enzymatic assembly based on light induced DNA scaffold switching. Via photocontrolled DNA conformational switching, the proximity of multiple enzyme catalytic centers can be adjusted, as well as the catalytic efficiency of cofactor-mediated DNAzymes. We expect that this approach will lead to the advancement of DNA-enzymatic functional nanostructures in future biomedical and analytical applications. PMID- 22098553 TI - Impacts of HIV infection and long-term use of antiretroviral therapy on the prevalence of oral human papilloma virus type 16. AB - BACKGROUND: The objectives of this study were to determine (i) the prevalence and the copy numbers of oral human papilloma virus type 16 (HPV-16) in HIV-infected patients compared with non-HIV controls, and (ii) the effects of antiretroviral therapy (ART) and its duration on the virus. METHODS: A cross-sectional study was carried out in HIV-infected patients with and without ART and in non-HIV controls. Saliva samples were collected, and the DNA extracted from those samples was used as a template to detect HPV-16 E6 and E7 by quantitative polymerase chain reaction. Student's t-test and ANOVA test were performed to determine the prevalence rates among groups. RESULTS: Forty-nine HIV-infected patients: 37 on ART (age range, 23-54 years; mean, 37 years), 12 not on ART (age range, 20-40 years; mean, 31 years), and 20 non-HIV controls (age range, 19-53 years; mean, 31 years) were enrolled. The prevalence of oral HPV-16 infection and the copy numbers of the virus were significantly higher in HIV-infected patients than in non-HIV controls when using E6 assay (geometric mean = 10696 vs. 563 copies/10(5) cells, P < 0.001), but not E7 assay. No significant difference was observed between those who were and were not on ART. Long-term use of ART did not significantly change the prevalence of oral HPV-16 infection and the copy numbers of the virus (P = 0.567). CONCLUSION: We conclude that the prevalence of oral HPV 16 infection and the copy numbers of the virus are increased by HIV infection. Neither the use of ART nor its duration significantly affected the virus. PMID- 22098554 TI - Nestin-positive hair follicle pluripotent stem cells can promote regeneration of impinged peripheral nerve injury. AB - Nestin-positive, keratin 15 (K15)-negative multipotent hair follicle stem cells are located above the hair follicle bulge. We have termed this location the hair follicle pluripotent stem cell area. We have previously shown that transplantation of nestin-expressing hair follicle stem cells can regenerate peripheral nerve and spinal cord injuries. In the present study, we regenerated the impinged sciatic nerve by transplanting hair follicle pluripotent stem cells. Human hair follicle stem cells were transplanted around the impinged sciatic nerve of ICR nude (nu/nu) mice. The hair follicle stem cells were transplanted between impinged sciatic nerve fragments of the mouse where they differentiated into glial fibrillary acidic protein-positive Schwann cells and promoted the recovery of pre-existing axons. The regenerated sciatic nerve functionally recovered. These multipotent hair follicle stem cells thereby provide a potential accessible, autologous source of stem cells for regeneration therapy of nerves degenerated by compression between bony or other hard surfaces. PMID- 22098555 TI - On the trail of a cereal killer: recent advances in Fusarium graminearum pathogenomics and host resistance. AB - The ascomycete fungal pathogen Fusarium graminearum (sexual stage: Gibberella zeae) causes the devastating head blight or scab disease on wheat and barley, and cob or ear rot disease on maize. Fusarium graminearum infection causes significant crop and quality losses. In addition to roles as virulence factors during pathogenesis, trichothecene mycotoxins (e.g. deoxynivalenol) produced by this pathogen constitute a significant threat to human and animal health if consumed in respective food or feed products. In the last few years, significant progress has been made towards a better understanding of the processes involved in F. graminearum pathogenesis, toxin biosynthesis and host resistance mechanisms through the use of high-throughput genomic and phenomic technologies. In this article, we briefly review these new advances and also discuss how future research can contribute to the development of sustainable plant protection strategies against this important plant pathogen. PMID- 22098556 TI - A stereocontrolled synthesis of (+)-saxitoxin. AB - A concise stereoselective total synthesis of (+)-saxitoxin is described. A silver(I)-initiated hydroamination cascade constructs the bicyclic guanidinium ion core from a alkynyl bisguanidine. This sequence creates two C-N bonds, one C O bond, and three rings and forms a single stereoisomer in a single synthetic transformation. This process enabled us to complete the synthesis of (+) saxitoxin in 14 steps from N-Boc-l-serine methyl ester. PMID- 22098557 TI - Gap junction-mediated calcium waves define communication networks among murine postnatal neural progenitor cells. AB - In the postnatal neurogenic niche, two populations of astrocyte-like cells (B cells) persist, one acting as neural progenitor cells (NPCs, B1 cells) and one forming a structural boundary between the neurogenic niche and the striatum (B2 cells, niche astrocytes). Despite being viewed as two distinct entities, we found that B1 and B2 cells express the gap junction protein connexin 43 and display functional coupling involving 50-60 cells. Using neonatal electroporation to label slowly cycling radial glia-derived B1 cells, which send a basal process onto blood vessels, we further confirmed dye coupling between NPCs. To assess the functionality of the coupling, we used calcium imaging in a preparation preserving the three-dimensional architecture of the subventricular zone. Intercellular calcium waves were observed among B cells. These waves travelled bidirectionally between B1 and B2 cells and propagated on blood vessels. Inter-B cell calcium waves were absent in the presence of a gap junction blocker but persisted with purinergic receptor blockers. These findings show that privileged microdomains of communication networks exist among NPCs and niche astrocytes. Such functional coupling between these two cell types suggests that niche astrocytes do not merely have a structural role, but may play an active role in shaping the behavior of NPCs. PMID- 22098558 TI - Effect of photochemical smog associated with synoptic weather patterns on cardiovascular and respiratory hospital admissions in metropolitan Taipei. AB - This study focuses on the relationship between photochemical smog (PS) (hourly ozone conc. >100 ppb), PS-related diseases, and the synoptic weather patterns during 2005-2009 in metropolitan Taipei. The results show that compared to respiratory ailments (ICD code 460-519) and asthma (ICD code 493), cardiovascular ailments (ICD code 390-459) were more clearly influenced by PS events. On the PS event day, the number of admissions of babies, children, and adults increased by 0.04 [95% CI 0.01-0.06], 0.03 [95% CI 0.00-0.07], and 1.12 [95% CI 0.36-1.89] (P < 0.05), respectively. The investigation showed that more than 70% of the PS events were associated primarily with the peripheral circulation of typhoons, Pacific pressure, and discrete Pacific pressure. PS events are a threat to public health. To avoid the ill effects of air pollution, residents should be informed about the daily weather patterns and air quality. PMID- 22098559 TI - Filarial and Wolbachia genomics. AB - Filarial nematode parasites, the causative agents for a spectrum of acute and chronic diseases including lymphatic filariasis and river blindness, threaten the well-being and livelihood of hundreds of millions of people in the developing regions of the world. The 2007 publication on a draft assembly of the 95-Mb genome of the human filarial parasite Brugia malayi- representing the first helminth parasite genome to be sequenced - has been followed in rapid succession by projects that have resulted in the genome sequencing of six additional filarial species, seven nonfilarial nematode parasites of animals and nearly 30 plant parasitic and free-living species. Parallel to the genomic sequencing, transcriptomic and proteomic projects have facilitated genome annotation, expanded our understanding of stage-associated gene expression and provided a first look at the role of epigenetic regulation of filarial genomes through microRNAs. The expansion in filarial genomics will also provide a significant enrichment in our knowledge of the diversity and variability in the genomes of the endosymbiotic bacterium Wolbachia leading to a better understanding of the genetic principles that govern filarial-Wolbachia mutualism. The goal here is to provide an overview of the trends and advances in filarial and Wolbachia genomics. PMID- 22098561 TI - Update of the original HDLS kindred: divergent clinical courses. AB - BACKGROUND: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was first identified among a Swedish kindred with 17 cases. The average age of onset was 36 years. Autopsy in four cases revealed the presence of axonal spheroids. The causative gene is unknown. METHODS: We performed genealogical and longitudinal observations of the original kindred. Forty members were examined, five telephone-interviewed, and one of the original HDLS cases from 1984 was neuropathologically examined. The clinical course was documented. The cerebrospinal fluid (CSF) findings of two recently affected cases were examined, and one of those autopsied. RESULTS: Of those examined, two developed HDLS during our survey and 38 were healthy. Those interviewed by telephone were healthy. One had symptoms suggestive of HDLS in 1984, but autopsy during our survey showed no spheroids. This patient, two relatives healthy at our examination and one without symptoms at telephone interview had HDLS diagnoses in the 1984 report. Thus, four HDLS diagnoses were unconfirmed. The number of identified patients amounts to 15 among 75 individuals in four generations, including two recent cases who demonstrated a subacute multisystem encephalopathy in Case 1 and an insidious course in Case 2. CSF showed signs of neurodegeneration without inflammation, and autopsy verified HDLS in Case 1. CONCLUSIONS: Some HDLS cases were misdiagnosed with unspecified psychiatric diagnoses in affected relatives from the original 1984 publication. However, HDLS is an encephalopathy dominated by a frontal lobe syndrome with an inexorably progressive and fatal course, where the different symptomatology in two recent cases confirmed the existence of acute and chronic variants. PMID- 22098560 TI - Reprogramming urokinase into an antibody-recruiting anticancer agent. AB - Synthetic compounds for controlling or creating human immunity have the potential to revolutionize disease treatment. Motivated by challenges in this arena, we report herein a strategy to target metastatic cancer cells for immune-mediated destruction by targeting the urokinase-type plasminogen activator receptor (uPAR). Urokinase-type plasminogen activator (uPA) and uPAR are overexpressed on the surfaces of a wide range of invasive cancer cells and are believed to contribute substantially to the migratory propensities of these cells. The key component of our approach is an antibody-recruiting molecule that targets the urokinase receptor (ARM-U). This bifunctional construct is formed by selectively, covalently attaching an antibody-binding small molecule to the active site of the urokinase enzyme. We demonstrate that ARM-U is capable of directing antibodies to the surfaces of target cancer cells and mediating both antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) against multiple human cancer cell lines. We believe that the reported strategy has the potential to inform novel treatment options for a variety of deadly, invasive cancers. PMID- 22098562 TI - Validity and reliability of a new field test (Carminatti's test) for soccer players compared with laboratory-based measures. AB - The aim of this study was to assess the validity (Study 1) and reliability (Study 2) of a novel intermittent running test (Carminatti's test) for physiological assessment of soccer players. In Study 1, 28 players performed Carminatti's test, a repeated sprint ability test, and an intermittent treadmill test. In Study 2, 24 players performed Carminatti's test twice within 72 h to determine test-retest reliability. Carminatti's test required the participants to complete repeated bouts of 5 * 12 s shuttle running at progressively faster speeds until volitional exhaustion. The 12 s bouts were separated by 6 s recovery periods, making each stage 90 s in duration. The initial running distance was set at 15 m and was increased by 1 m at each stage (90 s). The repeated sprint ability test required the participants to perform 7 * 34.2 m maximal effort sprints separated by 25 s recovery. During the intermittent treadmill test, the initial velocity of 9.0 km . h(-1) was increased by 1.2 km . h(-1) every 3 min until volitional exhaustion. No significant difference (P > 0.05) was observed between Carminatti's test peak running velocity and speed at VO(2max) (v-VO(2max)). Peak running velocity in Carminatti's test was strongly correlated with v-VO(2max) (r = 0.74, P < 0.01), and highly associated with velocity at the onset of blood lactate accumulation (r = 0.63, P < 0.01). Mean sprint time was strongly associated with peak running velocity in Carminatti's test (r = -0.71, P < 0.01). The intraclass correlation was 0.94 with a coefficient of variation of 1.4%. In conclusion, Carminatti's test appears to be avalid and reliable measure of physical fitness and of the ability to perform intermittent high-intensity exercise in soccer players. PMID- 22098563 TI - Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects. AB - CONTEXT: The relationship of monocyte/macrophage activation to insulin resistance in obesity is unknown. OBJECTIVE: To investigate a marker of macrophage activation, soluble CD163 (sCD163), in relationship to insulin resistance and metabolic parameters in obese and normal-weight subjects. DESIGN AND PARTICIPANTS: Ninety-five healthy subjects (65 obese and 30 normal-weight) were studied. Plasma concentrations of sCD163 were assessed, as well as markers of glucose homeostasis, anthropometrics, cytokines and adipokines. The relationships between sCD163 and these parameters were investigated, and multiple regression modelling assessing the contribution of sCD163 to insulin resistance (HOMA-IR) was performed. RESULTS: Soluble CD163 was significantly increased in obese subjects compared with normal-weight controls [974 (657, 1272) ng/ml vs 599 (423, 892) ng/ml, median (IQR); P < 0.0001]. sCD163 was strongly associated with HOMA IR (Spearman's rho = 0.37, P = 0.0003) and other metabolic parameters. In multiple regression modelling for log HOMA-IR, sCD163 remained significantly associated (P = 0.005) controlling for known mediators of insulin resistance including age, gender, visceral adiposity and inflammatory markers (model R(2) = 0.54, P < 0.0001). Additional nested multiple regression models for log HOMA-IR showed that sCD163 added more than other adipokines and inflammatory markers to the prediction of HOMA-IR. CONCLUSIONS: Monocyte/macrophage activation, as reflected by sCD163 levels, is strongly associated with HOMA-IR in normal-weight and obese subjects after controlling for known mediators of insulin resistance. Moreover, sCD163 adds to standard risk markers for predicting insulin resistance. These data suggest that monocyte/macrophage activation may be an important determinant of insulin resistance in obesity. PMID- 22098564 TI - High density lipoprotein in patients with liver failure; relation to sepsis, adrenal function and outcome of illness. AB - BACKGROUND AND AIMS: High density lipoprotein (HDL) plays an important role in the transport of cholesterol to the adrenal gland for steroidogenesis and may have actions that modulate response to infection and critical illness. The clinical relevance of HDL level in patients with liver failure remains poorly characterised. METHODS: In 164 critically-ill patients with acute (ALF) and acute on chronic liver failure (AOCLF) we evaluated the relationship between HDL levels measured on admission to intensive care unit (ICU) and survival, predisposition to sepsis and adrenocortical function assessed through the cortisol response to short synacthen testing (SST). RESULTS: In acute liver failure and acute on chronic liver failure, high density lipoprotein levels were significantly lower in non-survivors (P < 0.01). Levels correlated closely with biochemical markers of liver function and the duration of liver failure. However, predictive accuracy was not superior to conventional markers and on multi-variate analysis did not show independent association with survival. Low HDL concentration was not associated with an increased incidence of sepsis either precipitating or complicating ICU admission. Evidence of adrenocortical insufficiency was present in more than half of patients undergoing SST and HDL level but not other lipid parameters correlated closely with cortisol increment after SST (r = 0.364, P < 0.0001). CONCLUSIONS: High density lipoprotein levels are low in patients with liver failure and reflect its severity. Levels are lower in non-survivors but do not offer an advantage as early indicators of prognosis over conventional markers. No evidence of a major predisposing role for infection was found, but findings suggest a close link to adrenal function. PMID- 22098565 TI - The role of noninvasive imaging in early diagnosis of clinically masked prepulseless inflammatory phase of Takayasu's Arteritis. AB - Diagnosis of early-phase Takayasu's arteritis (TA) is extremely difficult and overlooked as most often presentation is nonspecific and mimics various other diseases. Early diagnosis and initiation of proper therapy could alter the natural course of the disease. We describe an adolescent male presenting with pyrexia of unknown origin and clinical features simulating idiopathic dilated cardiomyopathy. Transthoracic echocardiography was suggestive of dilated cardiomyopathy with severe left ventricular dysfunction. Later vascular ultrasonography and CT aortography showed extensive thickening of intima-media of aorta and its major branches suggestive of inflammatory phase of TA. We discuss the role of noninvasive imaging in diagnosis of clinically masked prepulseless inflammatory phase of TA. PMID- 22098566 TI - New preparation of benzylic aluminum and zinc organometallics by direct insertion of aluminum powder. AB - The reaction of commercial Al-powder (3 equiv) and InCl(3) (1-5 mol %) with benzylic chlorides provides various functionalized benzylic aluminum sesquichlorides under mild conditions (THF, 20 degrees C, 3-24 h) without homocoupling (<5%). These new benzylic organometallics reacted smoothly with various electrophiles (Pd-catalyzed cross-couplings, or Cu-mediated acylations, allylations, or 1,4-addition reactions). Electron-poor benzylic chlorides or substrates prone to Wurtz coupling can be converted to benzylic zinc compounds by the reaction of Al-powder in the presence of ZnCl(2). PMID- 22098567 TI - Modeling erotomania delusion in the laboratory with hypnosis. AB - Erotomania is the delusional belief that one is loved from afar by another person (the target). This study used hypnosis as a novel cognitive neuropsychological research tool to model erotomania. The authors developed 2 versions of a hypnotic erotomania suggestion and tested their impact by asking subjects to recall and interpret a story featuring ambiguous scenarios. They also challenged the delusion by asking subjects to justify their beliefs. The hypnotic erotomania suggestions successfully recreated the features of the clinical delusion for many high hypnotizable subjects. They believed that the target loved them, interpreted ambiguous information consistent with this belief and confabulated evidence in service of their delusion. Some also resisted all challenges to their delusion. These features are strikingly similar to clinical cases and highlight the value of using hypnosis to model clinical delusions. The authors also discuss some limitations of this approach. PMID- 22098568 TI - EEG sLORETA functional imaging during hypnotic arm levitation and voluntary arm lifting. AB - This study (N = 37 with high, medium, and low hypnotizables) evaluated depth reports and EEG activity during both voluntary and hypnotically induced left-arm lifting with sLORETA functional neuroimaging. The hypnotic condition was associated with higher activity in fast EEG frequencies in anterior regions and slow EEG frequencies in central-parietal regions, all left-sided. The voluntary condition was associated with fast frequency activity in right-hemisphere central parietal regions and slow frequency activity in left anterior regions. Hypnotizability did not have a significant effect on EEG activity, but hypnotic depth correlated with left hemisphere increased anterior slow EEG and decreased central fast EEG activity. Hypnosis had a minimal effect on depth reports among lows, a moderate one among mediums, and a large one among highs. Because only left-arm data were available, the full role of the hemispheres remains to be clarified. PMID- 22098569 TI - Hypnotizability-related differences in written language. AB - The study analyzed the writing products of subjects with high (highs) and low (lows) hypnotizability. The participants were asked to write short texts in response to highly imaginative scenarios in standard conditions. The texts were processed through computerized and manual methods. The results showed that the highs' texts were more sophisticated due to a higher number of abstract nouns, more intense and imaginative due to a larger number of similes, metaphors, and onomatopoeias, and less detailed due to a higher nouns-to-adjectives ratio. The differences in the use of abstract nouns and highly imageable expressions are discussed in relation to the preeminent left-hemisphere activity of highs during wakefulness and to a possibly different involvement of the precuneus, which is involved in hypnotic phenomena. PMID- 22098570 TI - The cognitive demands of hypnotic response. AB - This study tests the proposal that hypnotic responding is effortless. The authors compared the responses of high and low hypnotizable participants (N = 70) in and out of hypnosis on a dual-task paradigm in which they were required to maintain hypnotic blindness during presentation of visual stimuli of varying salience intensities while simultaneously completing a secondary task. Whereas high hypnotizable participants in both hypnosis and wake conditions reported comparable levels of conviction in the hallucination suggestion, hypnotized highs performed poorer on the secondary task when the stimulus was present. Performance on the secondary task deteriorated when the visual stimulus was intensified. These findings contradict the notion that hypnotic response is not demanding on cognitive resources and suggest that increased effort is required to resolve the extent of conflict between reality and suggestion. PMID- 22098571 TI - Cerebral blood flow evaluation during the hypnotic state with transcranial Doppler sonography. AB - Cerebral blood flow was measured in normal waking (alert relaxed mental imagery) and hypnotic states. Mean flow velocity (Vm) in the middle cerebral artery (MCA) was significantly increased in hypnosis (Condition II) from Condition I (5 minutes before hypnotic induction). Vm decreased in Condition III (hypnotic imagination). After hypnosis, Vm values returned to baseline. Pulsatility index values and resistive index values showed significant variations during sonographic monitoring between Conditions I and IV (5 minutes after the completion of hypnosis). Both values were significantly higher in Condition I than IV. These findings show that hypnotic status can modulate cerebral blood flow. PMID- 22098572 TI - Electromyographic investigation of hypnotic arm levitation: differences between voluntary arm elevation and involuntary arm levitation. AB - Thirty-three volunteers were randomly exposed to 3 conditions: hypnotic arm levitation, holding up the arm voluntarily without hypnosis, and imagined arm lifting without hypnosis. Trapezius, deltoid, extensor digitorum, flexor digitorum profundus, biceps brachii, and triceps brachii muscles were measured. Strain and muscle activity during lifting and holding up the right arm for 3 minutes were used as dependent variables. During hypnotic arm levitation, the total muscle activity was lower than during holding it up voluntarily (p < .01); the activity in the deltoid was 27% lower (p < .001). Without hypnosis, the muscle activity showed a positive correlation with strain. However, there was no such correlation in the hypnotic condition. Apparently, it is possible to reduce strain and to objectively measure muscle activity in an uplifted arm through hypnotic arm levitation. PMID- 22098573 TI - Hypnotherapy intervention for loin pain hematuria: a case study. AB - Loin pain hematuria is characterized by chronic loin pain, hematuria, and dysuria. There are no known effective treatments for loin pain hematuria and longer term use of analgesics and surgical options are often ineffective or associated with negative side effects. This article reports on a 17-year-old female patient diagnosed with loin pain hematuria who presented with unilateral, uncontrolled loin pain following numerous unsuccessful attempts at controlling her symptoms with traditional medical interventions, including antibiotics, opioids, and renal denervation. The patient received 8 sessions of hypnotherapy. Baseline, endpoint, and follow-up measures administered included the General Health Questionnaire, Hospital Anxiety and Depression Scale, McGill Pain Questionnaire, Pain Discomfort Scale, and visual analogue measures of pain, academic interference, and social interference. At follow-up, results indicated clinically significant decreases in pain, anxiety, and depression with nearly complete remission of presenting symptoms. PMID- 22098574 TI - Herbert Spiegel, MD, a man for all seasons: early personal and professional development, 1914-1946. AB - Herbert Spiegel, MD, was a pioneer in American psychiatry and the field of hypnosis, which he first started using as an army psychiatrist posted at Fort Meade, Maryland. He served as a battalion surgeon during the invasion of North Africa and later in the Tunisian campaign. On the battlefield, Spiegel used hypnosis for quick symptom resolution and pain control. He was wounded in action on May 7, 1943, and was awarded a Purple Heart for his courage and bravery. When Spiegel was evacuated back to America, he began writing about short-term treatment strategies based on cognitive restructuring, hypnosis, and other clinical techniques. This article details his early life and career. PMID- 22098575 TI - Conformational variability of organophosphorus hydrolase upon soman and paraoxon binding. AB - The bacterial enzyme organophosphorus hydrolase (OPH) exhibits both catalytic and substrate promiscuity. It hydrolyzes bonds in a variety of phosphotriester (P-O), phosphonothioate (P-S), phosphofluoridate (P-F), and phosphonocyanate (F-CN) compounds. However, its catalytic efficiency varies markedly for different substrates, limiting the broad-range application of OPH as catalyst in the bioremediation of pesticides and chemical war agents. In the present study, pK(a) calculations and multiple explicit-solvent molecular dynamics (MD) simulations were performed to characterize and contrast the structural dynamics of OPH bound to two substrates hydrolyzed with very distinct catalytic efficiencies: the nerve agent soman (O-pinacolylmethylphosphonofluoridate) and the pesticide paraoxon (diethyl p-nitrophenyl phosphate). pK(a) calculations for the substrate-bound and unbound enzyme showed a significant pK(a) shift from standard values (DeltapK(a) = +/-3 units) for residues His254 and Arg275. MD simulations of protonated His254 revealed a dynamic hydrogen bond network connecting the catalytic residue Asp301 via His254 to Asp232, Asp233, Arg275, and Asp235, and is consistent with a previously postulated proton relay mechanism to ferry protons away from the active site with substrates that do not require activation of the leaving group. Hydrogen bonds between Asp301 and His254 were persistent in the OPH-paraoxon complex but not in the OPH-soman one, suggesting a potential role for such interaction in the more efficient hydrolysis of paraoxon over soman by OPH. These results are in line with previous mutational studies of residue His254, which led to an increase of the catalytic efficiency of OPH over soman yet decreased its efficiency for paraoxon. In addition, comparative analysis of the molecular trajectories for OPH bound to soman and paraoxon suggests that binding of the latter facilitates the conformational transition of OPH from the open to the closed substate promoting a tighter binding of paraoxon. PMID- 22098576 TI - Protein candidates for Q fever serodiagnosis. AB - The discriminatory diagnosis of Q fever remains difficult because of the unspecific clinical presentations of the disease. Additionally, the diagnosis is often delayed because serodiagnosis is not sensitive enough in the early stages of the disease when the immune response is not yet efficient. Similarly, the diagnosis of Q fever endocarditis can only be performed in approximately 35%, mainly via serology, which was a criterion postulated by Duke. Owing to the discriminatory diagnosis of Q fever and the high number of tests requested, we focused on expressing several proteins for ELISA studies with Coxiella burnetii infected sera. Previously, we selected a list of 31 candidates [Sekeyova et al. (2009) Eur J Clin Microbiol Infect Dis 28: 287-295], of which we have successfully cloned and expressed 21. Finally, 15 recombinant proteins were prescreened with the sera of patients with acute Q fever and Q fever endocarditis, respectively. Sera from a control group were also screened. The nine most immunoreactive proteins from the first assay were tested with the sera from a larger group of patients. Our study identified CBU_0092 as the best marker of acute Q fever but failed to isolate a highly specific and sensitive marker of Q fever endocarditis. PMID- 22098583 TI - Can cell death biomarkers predict the outcome of acute liver failure? PMID- 22098584 TI - Bilingualism and academic achievement. AB - Using the Early Childhood Longitudinal Study, Kindergarten Cohort, this study examines the role that bilingualism plays in children's academic developmental trajectories during their early school years, with particular attention on the school environment (N = 16,380). Growth-curve results showed that despite starting with lower math scores in kindergarten, Mixed Bilingual children fully closed the math gap with their White English Monolingual peers by fifth grade. However, because non-English-Dominant Bilinguals and non-English Monolinguals started kindergarten with significantly lower reading and math scores compared to their English Monolingual peers, by fifth grade the former groups still had significantly lower scores. School-level factors explained about one third of the reductions in the differences in children's academic performance. PMID- 22098585 TI - Experiences of abdominal massage for constipation. AB - AIM: This study aims to illuminate participants' experiences of receiving abdominal massage for constipation. BACKGROUND: Abdominal massage has been found to decrease the severity of constipation and abdominal pain, but little is known about how patients experience receiving abdominal massage. DESIGN: The present study is a qualitative descriptive study, based on individual interviews. METHOD: Nine adults receiving abdominal massage for constipation were invited to participate. Semi-structured interviews were conducted in Sweden between 2005 2007. The interviews were transcribed and subjected to qualitative content analysis. RESULTS: Four themes were formulated: 'being on one's guard', 'becoming embraced by safe hands', 'being touched physically and emotionally' and 'feeling vulnerable'. The participants reported that they were on guard, i.e. they were sceptical about whether or not abdominal massage was effective and suitable. However, as the massage sessions continued, they found the massage pleasant and began to feel embraced and in safe hands. They described how the abdominal massage made them feel as 'being touched physically and emotionally' and their bowel habits were improved. Along with the improvements, their agony was gone and they felt relieved. However, they considered their new condition fragile and they felt vulnerable to relapse. CONCLUSIONS: Abdominal massage was experienced as pleasurable, and after treatment, the participants felt more comfortable with their bowel function. Participants described abdominal massage as affecting the whole person. RELEVANCE TO CLINICAL PRACTICE: Abdominal massage has been shown to be an effective intervention for constipation. A crucial aspect is that nurses need to be sensitive and respect the intimacy associated with the abdomen. PMID- 22098586 TI - Crystalline assemblies and densest packings of a family of truncated tetrahedra and the role of directional entropic forces. AB - Polyhedra and their arrangements have intrigued humankind since the ancient Greeks and are today important motifs in condensed matter, with application to many classes of liquids and solids. Yet, little is known about the thermodynamically stable phases of polyhedrally shaped building blocks, such as faceted nanoparticles and colloids. Although hard particles are known to organize due to entropy alone, and some unusual phases are reported in the literature, the role of entropic forces in connection with polyhedral shape is not well understood. Here, we study thermodynamic self-assembly of a family of truncated tetrahedra and report several atomic crystal isostructures, including diamond, beta-tin, and high-pressure lithium, as the polyhedron shape varies from tetrahedral to octahedral. We compare our findings with the densest packings of the truncated tetrahedron family obtained by numerical compression and report a new space-filling polyhedron, which has been overlooked in previous searches. Interestingly, the self-assembled structures differ from the densest packings. We show that the self-assembled crystal structures can be understood as a tendency for polyhedra to maximize face-to-face alignment, which can be generalized as directional entropic forces. PMID- 22098587 TI - Antiadipogenic effect of dietary apigenin through activation of AMPK in 3T3-L1 cells. AB - Adipocyte differentiation (adipogenesis) is a complex process including the coordinated changes in hormone sensitivity and gene expression in response to various stimuli. Natural compounds are known to be involved in the regulation of this process. Here we investigated the effects of dietary apigenin, a plant flavonoid, on adipogenesis. Apigenin suppressed adipocyte differentiation of mouse adipocytic 3T3-L1 cells and reduced the accumulation of intracellular lipids. Quantitative PCR and Western blot analyses revealed that apigenin decreased the levels of peroxisome proliferator-activated receptor gamma and its target genes such as fatty acid binding protein 4 (aP2) and stearoyl-CoA desaturase. Apigenin decreased or had no effect on the expression of lipolytic genes such as adipose triglyceride lipase, hormone sensitive lipase, and monoacyl glyceride lipase, thereby reducing glycerol release from adipocytes. Noteworthily, apigenin activated 5'-adenosine monophosphate-activated protein kinase (AMPK) in an apigenin dose-dependent manner, which activation is known to suppress adipogenesis. These results provide a novel insight into the molecular mechanism involved in the action of apigenin: the apigenin-induced activation of AMPK leads to decreased expression of adipogenic and lipolytic genes, thus suppressing adipogenesis in 3T3-L1 cells. Thus, dietary apigenin may contribute to lower body-fat content and body-weight gain through the activation of AMPK. PMID- 22098588 TI - Development and evaluation of an information booklet about breast cancer and early menopause. PMID- 22098589 TI - Ethionamide boosters. 2. Combining bioisosteric replacement and structure-based drug design to solve pharmacokinetic issues in a series of potent 1,2,4 oxadiazole EthR inhibitors. AB - Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. We recently reported structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors leading to the discovery of potent ethionamide boosters. Despite high metabolic stability, pharmacokinetic evaluation revealed poor mice exposure; therefore, a second phase of optimization was required. Herein a structure-property relationship study is reported according to the replacement of the two aromatic heterocycles: 2-thienyl and 1,2,4-oxadiazolyl moieties. This work was done using a combination of structure-based drug design and in vitro/ex vivo evaluations of ethionamide boosters on the targeted protein EthR and on the human pathogen Mycobacterium tuberculosis. Thanks to this process, we identified compound 42 (BDM41906), which displays improved efficacy in addition to high exposure to mice after oral administration. PMID- 22098591 TI - Mitochondrial transcription factor A regulates BCL2L1 gene expression and is a prognostic factor in serous ovarian cancer. AB - Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA (mtDNA). Recently, we reported that mtTFA is expressed not only in mitochondria, but also in nuclei. However, the function of mtTFA in the nucleus has not been clearly elucidated. In the present study, we examined nuclear mtTFA expression in 60 tissue samples of serous ovarian cancer using immunohistochemical analysis and found that 56.7% of serous ovarian cancer patients were positive for mtTFA, whereas 43.3% were negative. Univariate survival analysis showed that the overall 5-year survival rate was significantly worse for patients with mtTFA-positive cancer compared with mtTFA-negative cancer (32%vs 42%, respectively; P = 0.021). To elucidate the function of mtTFA in the nucleus, we investigated BCL2L1, a target gene of mtTFA. There was a significant correlation between nuclear mtTFA expression and BCL2L1 expression in seven ovarian cancer cell lines and in specimens of clinical ovarian cancer. Cellular BCL2L1 was downregulated following transfection of siRNA against mtTFA. BCL2L1 promoter activity was increased after transfection of mtTFA expression plasmid, but decreased after siRNA knockdown of mtTFA. Chromatin immunoprecipitation assays showed that mtTFA was bound to the BCL2L1 promoter region. These results suggest that mtTFA is a prognostic factor for a poor outcome of ovarian cancer and may function as an antiapoptotic factor, regulating genes such as BCL2L1. Furthermore, mtTFA may be a promising molecular target for novel therapeutic strategies for the treatment of ovarian cancer. PMID- 22098590 TI - Predicting the efficacy of proton pump inhibitors in patients with non-erosive reflux disease before therapy using dual-channel 24-h esophageal pH monitoring. AB - BACKGROUND AND AIM: We aimed to determine whether reflux- and symptom-related parameters can predict the efficacy of proton pump inhibitors (PPI) in non erosive reflux disease (NERD). METHODS: Twenty-seven NERD patients who had experienced heartburn more than once a week within the previous month were enrolled. Intraesophageal pH before therapy was measured simultaneously at 5 and 15 cm above the esophagogastric junction (EGJ) for 24 h. The PPI rabeprazole was administered at a dose of 10 mg once daily for 4 weeks. In the event that heartburn was not relieved, the dose was increased to 10 mg twice daily for an additional 2 weeks, and again to 20 mg twice daily for another 2 weeks. RESULTS: Univariate analysis demonstrated no significant associations between any reflux- or symptom-related parameters at either site and complete heartburn relief after 4 weeks, or cumulative complete heartburn relief after 8 weeks. However, post-hoc analysis demonstrated more satisfactory heartburn relief after 4 weeks in patients with a high symptom index compared with those with a low symptom index, at 5 cm above the EGJ (P = 0.009). Cumulative satisfactory heartburn relief after 8 weeks was also greater in patients with a high total number of acid reflux episodes compared with those with a low total number of episodes, at 15 cm above the EGJ (P = 0.037). CONCLUSIONS: Pre-therapeutic pH monitoring in the lower and mid-esophagus is useful for predicting the efficacy of PPI in NERD patients. PMID- 22098592 TI - Connexin 26 (GJB2) mutations in keratitis-ichthyosis-deafness syndrome presenting with squamous cell carcinoma. PMID- 22098593 TI - Comparison of manual and digital microvascular density counting of RECK expression in glioma. AB - A microvascular density (MVD) counting method for reversion-inducing cysteine rich protein with Kazal motifs (RECK) expression, using a digital image analysis tool, has advantages over manual counting by microscope. Thirty glioma cases with RECK staining were photographed at a magnification of 200* high power field and the photographs in RGB images were analyzed, and stained vessels were captured and were counted automatically. MVD with RECK expression using a digital image analysis tool showed comparable results to those of the manual method. RECK intensity expression could show linear correlation with grades of glioma by the digital method, which was superior compared to the manual method. The present method is recommended to researchers undertaking MVD study for glioma. PMID- 22098594 TI - The effects of landscape fragmentation on pollination dynamics: absence of evidence not evidence of absence. AB - Animal-mediated pollination is essential for both ecosystem services and conservation of global biodiversity, but a growing body of work reveals that it is negatively affected by anthropogenic disturbance. Landscape-scale disturbance results in two often inter-related processes: (1) habitat loss, (2) disruptions of habitat configuration (i.e. fragmentation). Understanding the relative effects of such processes is critical in designing effective management strategies to limit pollination and pollinator decline. We reviewed existing published work from 1989 to 2009 and found that only six of 303 studies considering the influence of landscape context on pollination separated the effects of habitat loss from fragmentation. We provide a synthesis of the current landscape, behavioural, and pollination ecology literature in order to present preliminary multiple working hypotheses explaining how these two landscape processes might independently influence pollination dynamics. Landscape disturbance primarily influences three components of pollination interactions: pollinator density, movement, and plant demography. We argue that effects of habitat loss on each of these components are likely to differ substantially from the effects of fragmentation, which is likely to be more complex and may influence each pollination component in contrasting ways. The interdependency between plants and animals inherent to pollination systems also has the possibility to drive cumulative effects of fragmentation, initiating negative feedback loops between animals and the plants they pollinate. Alternatively, due to their asymmetrical structure, pollination networks may be relatively robust to fragmentation. Despite the potential importance of independent effects of habitat fragmentation, its effects on pollination remain largely untested. We postulate that variation across studies in the effects of 'fragmentation' owes much to artifacts of the sampling regimes adopted, particularly (1) incorrectly separating fragmentation from habitat loss, and (2) mis-matches in spatial scale between landscapes studied and the ecological processes of interest. The field of landscape pollination ecology could be greatly advanced through the consideration and quantification of the matrix, landscape functional connectivity, and pollinator movement behaviour in response to these elements. Studies designed to disentangle the independent effects of habitat loss and fragmentation are essential for gaining insight into landscape-mediated pollination declines, implementing effective conservation measures, and optimizing ecosystem services in complex landscapes. PMID- 22098595 TI - A catalytic tethering strategy: simple aldehydes catalyze intermolecular alkene hydroaminations. AB - Herein we describe a catalytic tethering strategy in which simple aldehyde precatalysts enable, through temporary intramolecularity, room-temperature intermolecular hydroamination reactivity and the synthesis of vicinal diamines. The catalyst allows the formation of a mixed aminal from an allylic amine and a hydroxylamine, resulting in a facile intramolecular hydroamination event. The promising enantioselectivities obtained with a chiral aldehyde also highlight the potential of this catalytic tethering approach in asymmetric catalysis and demonstrate that efficient enantioinduction relying only on temporary intramolecularity is possible. PMID- 22098596 TI - Acute transient thyroid swelling after fine-needle aspiration biopsy: three cases during only 6 weeks - a rare complication? PMID- 22098597 TI - Echocardiographically detected fibrinous sheaths associated with central venous catheters. AB - Several million catheters are annually placed in the United States and worldwide for a multitude of clinical conditions. Potential delayed complications relating to central venous catheters include infections, thrombosis and fibrin sheath formation. Fibrin sheaths form frequently around central catheters but seldom cause clinical symptoms by themselves that warrant further investigation. It is likely that with the advent of echocardiographic imaging techniques, these "sleeves" get detected more often, which may result in early and correct diagnosis of this potential hazardous condition. Retained fibrin sleeves can cause malfunction of indwelling catheters, can persist after removal of the catheter, and be a nidus for thrombus formation or vegetation with a potential for distal embolization. Future research directed at creating new coatings with cytotoxic or cytostatic agents is warranted to reduce the incidence of fibrin sheath formation and hence prevent potential complications. We report three cases of persistent fibrin sheaths forming at the site of previously inserted tunneled catheters two of which were complicated by thrombus formation and vegetations. PMID- 22098598 TI - Synovial sarcoma of the cauda equina. AB - Primary synovial sarcoma originating from the cauda equina is extremely rare. Only one case, involving an 11-year-old girl, has been reported. The authors describe the case of a 23-year-old woman with a primary synovial sarcoma of the cauda equina. The patient visited a local hospital and described a 2-month history of low-back pain. She was referred to the authors' hospital for further evaluation. On physical examination, she had a straight-leg raising result of 70 degrees bilaterally. Motor examination revealed Grade 4/5 strength in the bilateral extensor hallux longus muscles. There was normal sensation to light touch and vibration in the lower extremities. Sagittal Gd-enhanced T1-weighted MR imaging demonstrated an intradural, extramedullary, and uniformly enhancing mass that extended from L-3 to L-4. The mass was totally resected and adjuvant local radiation therapy was administered. Reverse transcriptase polymerase chain reaction (RT-PCR) of a paraffin-embedded tissue sample revealed SYT-SSX fusion transcripts, and the diagnosis of synovial sarcoma was confirmed. Five and a half years after surgery, the patient is free of local recurrence and metastatic disease. The RT-PCR detection of SYT-SSX fusion transcripts played a key role in establishing the diagnosis of synovial sarcoma of the cauda equina. Complete resection of the mass with adjuvant local radiation therapy proved to be effective. PMID- 22098599 TI - Giant-cell granuloma of the axis. AB - Giant-cell granuloma is a benign and nonneoplastic lesion with an expansive and locally destructive behavior. It typically involves the mandible and the maxilla. Only 1 case arising from the odontoid process of the axis has been reported previously. The authors report on a 64-year-old man with a giant-cell granuloma of the axis. They review this uncommon entity, emphasizing the complexity of differentiating between this lesion and other giant-cell tumors. PMID- 22098600 TI - Spine clearance. PMID- 22098601 TI - Survival for colon and rectal cancer in Estonia: role of staging and treatment. AB - BACKGROUND: International comparisons have indicated low colorectal cancer (CRC) survival in Estonia, compared to other European countries. The objective of this paper is to analyse long-term survival as well as staging and treatment patterns of CRC in Estonia. MATERIAL AND METHODS: The analysis included all incident cases of CRC diagnosed in Estonia in 1997 (n = 546), identified through the Estonian Cancer Registry and followed up for 10 years after diagnosis. Staging and treatment data were retrospectively collected from medical records. Relative survival rate (RSR) was used to estimate the outcome. RESULTS AND CONCLUSION: The 5-year RSR was 51% for colon cancer and 38% for rectal cancer; the corresponding 10-year RSR was 50% and 39%. We observed no excess mortality for early disease. For stages II and III, the survival was markedly higher in colon cancer (5-year RSR 79% and 66%, respectively) compared to rectal cancer (66% and 30%, respectively). Around 30% of cases were diagnosed with distant disease. Among radically operated colon and rectal cancer patients, the 10-year RSR was 90% and 70%, respectively. Most patients with available pathological information had one to four lymph nodes examined. Survival has notably improved for colon cancer, but not for rectal cancer in Estonia. High proportion of cases with distant metastasis at first diagnosis along with inadequate staging and low proportion of patients treated with curatively intended surgery and appropriate chemotherapy and radiotherapy may have contributed to this outcome. Progress could be achieved by earlier diagnosis and implementing higher standards for staging and treatment. These conclusions are likely to be relevant also for other Eastern European countries. PMID- 22098602 TI - Modulation of neuromagnetic responses to face stimuli by preceding biographical information. AB - When we encode faces in memory, we often do so in association with biographical information regarding the person. To examine the neural dynamics underlying such encoding processes, we devised a face recognition task and recorded cortical activity using magnetoencephalography. The task included two conditions. In the experimental condition, face stimuli were preceded by biographical information regarding the person whose face was to be memorized, whereas in the control condition, nonsense syllables were presented before face stimuli. Behavioral results indicated that the biographical information about a person facilitated the recognition memory of their face. Magnetoencephalography signals showed clear visually evoked magnetic fields mainly in the occipitotemporal cortex, in response to the face stimuli that were to be encoded. The phasic peak was observed at 100-200 ms after onset of a face stimulus, which was followed by late latency deflections (200-400 ms). Comparison of the signal between conditions revealed that the preceding semantic information does modulate the neuromagnetic responses to the face stimuli. This modulation occurred primarily at the late latency component in the sensors over the occipitotemporal cortex. In addition, the effects of conditions were also observed in the signals from more anterior sensors, which occurred earlier than the effects in the occipitotemporal cortex. These results provide insights into the neural dynamics underlying the encoding of faces in association with their biographical information. PMID- 22098604 TI - Variation and evolution of the ABC transporter genes ABCB1, ABCC1, ABCG2, ABCG5 and ABCG8: implication for pharmacogenetics and disease. AB - The ATP-binding cassette (ABC) transporter genes are ubiquitous in the genomes of all vertebrates. Some of these transporters play a key role in xenobiotic defense and are endowed with the capacity to efflux harmful toxic substances. A major role in the evolution of the vertebrate ABC genes is played by gene duplication. Multiple gene duplication and deletion events have been identified in ABC genes, resulting in either gene birth or gene death indicating that the process of gene evolution is still ongoing in this group of transporters. Additionally, polymorphisms in these genes are linked to variations in expression, function, drug disposition and drug response. Single nucleotide polymorphisms in the ABC genes may be considered as markers of individual risk for adverse drug reactions or susceptibility to complex diseases as they can uniquely influence the quality and quantity of gene product. As the ABC genes continue to evolve, globalization will yield additional migration and racial admixtures that will have far reaching implications for the pharmacogenetics of this unique family of transporters in the context of human health. PMID- 22098603 TI - Gene-specific alterations of hepatic gene expression by ligand activation or hepatocyte-selective inhibition of retinoid X receptor-alpha signalling during inflammation. AB - BACKGROUND: Inflammation leads to transcriptional downregulation of many hepatic genes, particularly those activated by retinoid X receptor-alpha (RXRalpha) heterodimers. Inflammation-mediated reduction of nuclear RXRalpha levels is a main factor in reduced nuclear receptor (NR)-regulated hepatic gene expression, eventually leading to cholestasis and liver damage. AIM: To investigate roles for RXRalpha in hepatic gene expression during inflammation, using two complementary mouse models: ligand activation of RXRalpha, and in mice expressing hepatocyte specific expression of RXRalpha missing its DNA-binding domain (DBD; hs RxralphaDeltaex4(-/-) ). METHODS: To activate RXRalpha, mice were gavage-fed with LG268 or vehicle for 5 days. To inhibit RXRalpha function, hs-RxralphaDeltaex4(-/ ) mice were used. All mice were injected intraperitoneally with lipopolysaccharides (LPS) or saline for 16 h prior to analysis of hepatic RNA, protein and NR-DNA binding. RESULTS: LG268 treatment attenuated the LPS-mediated reductions of several RXRalpha-regulated genes, coinciding with maintained RXRalpha occupancy in both Bsep and Ostbeta promoters. Lacking full hepatocyte RXRalpha function (hs-RxralphaDeltaex4(-/-) mice) led to enhancement of LPS mediated changes in gene expression, but surprisingly, maintenance of RNA levels of some RXRalpha-regulated genes. Investigations revealed that hs RxralphaDeltaex4(-/-) hepatocytes expressed an internally truncated, approximately 44 kDa, RXRalpha-form. DNA-binding capacity of NR heterodimers was equivalent in wild-type and hs-RxralphaDeltaex4(-/-) livers, but reduced by LPS in both. Chromatin immunoprecipitation quantitative PCR revealed that RXRalpha occupancy to the Bsep RXRalpha:Farnesoid X Receptor site was reduced, but not absent, in hs-RxralphaDeltaex4(-/-) livers. CONCLUSIONS: There are differential regulatory roles for hepatic RXRalpha, both in basal and inflammatory states, suggesting new and complex multidomain roles for RXRalpha in regulating hepatic gene expression. Moreover, there is an unexpected non-obligate role for the DBD of RXRalpha. PMID- 22098605 TI - Linking genetic diversity and temporal fluctuations in population abundance of the introduced feral cat (Felis silvestris catus) on the Kerguelen archipelago. AB - Linking temporal variations of genetic diversity, including allelic richness and heterozygosity, and spatio-temporal fluctuations in population abundance has emerged as an important tool for understanding demographic and evolutionary processes in natural populations. This so-called genetic monitoring was conducted across 12 consecutive years (1996-2007) at three sites for the feral cat, introduced onto the Kerguelen archipelago fifty years ago. Temporal changes in allelic richness and heterozygosity at 18 microsatellite DNA loci were compared with temporal changes in the adult population abundance index, obtained by typical demographic monitoring. No association was found at the island spatial scale, but we observed an association between genetic diversity and adult population indices from year to year within each study site. More particularly, the magnitude of successive increases or decreases in the adult population abundance index appeared to be the major factor linking the trajectories of genetic diversity and adult population abundance indices. Natal dispersal and/or local recruitment, both facilitated by high juvenile survival when the adult population size is small, is proposed as the major demographic processes contributing to such an observed pattern. Finally, we suggested avoiding the use of the harmonic mean as an estimator of long-term population size to study the relationships between demographic fluctuations and heterozygosity in populations characterized by strong multiannual density fluctuations. PMID- 22098606 TI - The lack of memory B cells including T cell independent IgM+ IgD+ memory B cells in chronic graft-versus host disease is associated with susceptibility to infection. AB - The chronic graft-versus host disease (cGVHD) is associated with a perturbed B cell homeostasis and an increased infection rate. Aiming to determine the impact of lymphocyte subsets on cGVHD, blood samples from 98 patients at least 100 days following allogeneic haematopoietic stem cell transplantation (median 1066 days) were analyzed, serum levels of immunoglobulins measured and the incidence of severe infections retrospectively documented. Absolute CD19(+) B cell counts, including counts of immature (CD10(+) CD38(++) CD20(+) IgM(++)) and transitional (CD10(-) CD38(++) CD20(+) IgM(++)) as well as class switched memory (CD19(+) CD27(+) IgM(-) IgD(-)) B cells in patients with active cGVHD (n = 52) were significantly decreased as compared to those with inactive (n = 18) or without cGVHD (n = 28). In addition, nonclass switched IgM(+) memory B cells (CD19(+) CD27(+) IgM(+) IgD(+)) were absent in patients with cGVHD, but not in patients with inactive (0.4 * 10(6) /l) or without (1.7 * 10(6) /l) cGVHD (both P < 0.001). In line with these results we found significantly decreased lgG levels in patients with cGVHD, which was associated with a significantly higher rate of severe infections in cGVHD patients. Our data underline the close association of diminished B cell counts with cGVHD and the onset of severe infections. The lack of IgM(+) memory B cells in patients with cGVHD may indicate functional asplenia. PMID- 22098607 TI - Levofloxacin-induced rhabdomyolysis in a hemodialysis patient. AB - Rhabdomyolysis is a well-known complication of various drug therapies. We report a case of levofloxacin-induced rhabdomyolysis requiring hospitalization in a hemodialysis patient. Physicians should be aware of the risk of this potentially severe adverse drug reaction. PMID- 22098608 TI - Asymmetric hydrogenation of 2- and 2,3-substituted quinoxalines with chiral cationic ruthenium diamine catalysts. AB - The enantioselective hydrogenation of 2-alkyl- and 2-aryl-subsituted quinoxalines and 2,3-disubstituted quinoxalines was developed by using the cationic Ru(eta(6) cymene)(monosulfonylated diamine)(BArF) system in high yields with up to 99% ee. The counteranion was found to be critically important for the high enantioselectivity and/or diastereoselectivity. PMID- 22098609 TI - Hepatoprotective effects of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone on CCl4-induced acute liver injury in mice. AB - In this paper, the hepatoprotective effects of 2',4'-dihydroxy-6'-methoxy-3',5' dimethylchalcone (DMC) on CCl(4)-induced acute liver injury in Kunming mice were investigated. DMC was administered intraperitoneally (ip) (5, 10, or 20 mg/kg of body weight) for 7 days prior to the administration of CCl(4) (0.1%, ip). Pretreatment with DMC significantly decreased activities of serum hepatic enzymes, namely alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin, and decreased the elevation of lipid peroxidation, malondialdehyde, reactive oxygen species, and protein carbonyl content. Pretreatment with DMC markedly increased activities of enzymatic antioxidants such as superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase and increased levels of nonenzymatic antioxidant markers such as reduced glutathione, total sulfhydryl groups, vitamin C, and vitamin E in liver. These results combined with liver histopathology demonstrate that DMC has potential hepatoprotective effects, which may be related to the attenuation of oxidative stress, accelerating the antioxidant cascade and inhibition of lipid peroxidation. PMID- 22098610 TI - Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C. AB - BACKGROUND AND AIM: HFE mutations, a common cause of hereditary hemochromatosis (HH), are reportedly associated with hepatic iron overload, severe liver fibrosis, and good response to interferon treatment in European patients with chronic hepatitis C (CHC). HH shows ethnicity-based differences and little is known about the effects of HH mutations on CHC in the Japanese. Thus, the aim of this study was to clarify the clinical influence of HFE mutations in Japanese CHC patients. METHODS: In a total of 251 patients with CHC, we analyzed the frequencies of H63D and S65C mutations in the HFE gene, and the influence of these mutations on clinical parameters and response to pegylated-interferon-alpha 2b (PEG-IFN) plus ribavirin therapy. RESULTS: Fourteen patients (5.6%) carried the H63D mutation; all were heterozygotes. No S65C mutations were found. Only hemoglobin levels in the H63D heterozygotes were higher than in wild-type patients. Eleven of 14 H63D heterozygotes achieved sustained virological response (SVR). On univariate analysis, factors associated with SVR were interleukin 28B (IL28B) polymorphism, age, hepatitis C virus (HCV) genotype, HCV viral load, white blood cell count, stage of fibrosis and H63D mutation. All patients with both TT genotype in IL28B (rs8099917) and H63D mutation in HFE (n = 10) achieved SVR. CONCLUSIONS: The H63D mutation has little impact on the clinical characteristics of CHC, but is related to favorable response to PEG-IFN plus ribavirin therapy, particularly in patients with the TT allele in IL28B. PMID- 22098611 TI - Cytotoxic withanolide constituents of Physalis longifolia. AB - Fourteen new withanolides, 1-14, named withalongolides A-N, respectively, were isolated from the aerial parts of Physalis longifolia together with eight known compounds (15-22). The structures of compounds 1-14 were elucidated through spectroscopic techniques and chemical methods. In addition, the structures of withanolides 1, 2, 3, and 6 were confirmed by X-ray crystallographic analysis. Using a MTS viability assay, eight withanolides (1, 2, 3, 7, 8, 15, 16, and 19) and four acetylated derivatives (1a, 1b, 2a, and 2b) showed potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal fibroblast (MRC-5) cells with IC50 values in the range between 0.067 and 9.3 MUM. PMID- 22098612 TI - Iron metabolism and the role of HFE gene polymorphisms in Wilson disease. AB - Wilson disease (WD) is a rare inherited disorder of copper metabolism, which can lead to severe liver failure and to a variety of neuropsychiatric symptoms. Previous animal studies and case reports suggest that hepatic iron overload and alterations in iron processing are associated with WD. The aim of this study was the assessment of iron metabolism and of the frequency of the most common HFE gene polymorphisms in WD patients. PATIENTS AND METHODS: Data from 143 patients with WD were analysed. Clinical presentation, liver function and iron metabolism parameters were recorded. Blood samples of the patients were analysed for HFE gene alterations (H63D; C282Y). Twenty-seven liver biopsies of these patients were studied with regard to iron content and fibrosis score. RESULTS: Contrary to previous reports of HFE gene polymorphisms in WD patients, in our cohort the allele frequencies (C282Y: 2.1%; H63D: 7.3%) were in line with frequencies obtained for general population. Male WD patients with decreased serum ceruloplasmin (Cp), showed increased serum ferritin levels. Hepatic iron content was normal in most cases. DISCUSSION: Male patients with very low Cp serum concentrations showed slightly elevated median serum ferritin concentrations, probably related to lack of ferroxidase acitivity. However, in consideration of absolute numbers of ferritin concentrations, these changes seem to be of minor clinical relevance. PMID- 22098613 TI - Maternal serum interleukin-6 and its association with clinicopathological infectious morbidity in preterm premature rupture of membranes: a prospective cohort study. AB - OBJECTIVE: To analyze the association of maternal serum interleukin-6 (IL-6) with fetomaternal outcome in preterm premature rupture of membranes (PPROM). METHODS: Serial serum IL-6 levels were measured in 45 women with PPROM at gestation 24-34 weeks. The women were followed till pueperium and fetomaternal outcome as well as the histopathology of the placenta and the umbilical cord was studied. The data were analyzed using t test and chi(2) test. RESULTS: IL-6 levels >= 8 pg/ml were significantly associated with puerperal sepsis and neonatal sepsis. Histological chorioamnionitis and funisitis were demonstrated in 48.8% and 13.3% women respectively and significantly correlated with elevated serum IL-6 levels and fetomaternal infection. A cut-off value of IL-6 of 8 pg/ml was found to correctly diagnose 19 out of 23 patients with infectious morbidity and showed the best sensitivity (82.6%) and specificity (86.3%) as compared to the total leucocycte count (TLC) and C-reactive protein (CRP) in diagnosing infection in PPROM. CONCLUSION: Maternal serum IL-6 can be used as a biomarker to predict preclinical asymptomatic infection in PPROM with good sensitivity and specificity. PMID- 22098614 TI - Growth hormone, dehydroepiandrosterone and adiponectin levels in non-alcoholic steatohepatitis: an endocrine signature for advanced fibrosis in obese patients. AB - BACKGROUND AND AIMS: Liver-related clinical consequences of non-alcoholic fatty liver disease (NAFLD) are seen only in the minority of patients with advanced fibrosis. The aim of our study was to generate insight into a potential endocrine basis of steatohepatitis with advanced fibrosis in NAFLD. METHODS: Biopsy and blood samples were prospectively collected from patients with medically complicated obesity. Patients were categorized, according to liver histology, into: (i) normal, (ii) simple steatosis (SS), (iii) non-alcoholic steatohepatitis (NASH) with fibrosis stage (FS) 0-1 and (iv) NASH with FS >= 2. A broad panel of potential biomarkers included DHEA-S, growth hormone (GH), homeostasis model assessment-insulin resistance (HOMA-IR), leptin, resistin, adiponectin and cytokeratin 18 (CK-18) fragments. RESULTS: We studied 160 patients (mean BMI 46.8 +/- 8.2 kg/m(2) ). Liver biopsies demonstrated normal histology in 10%, SS in 45%, NASH with FS 0-1 in 37.5% and NASH with FS >= 2 in 7.5%. C-reactive protein, IL-6, GH, CK-18, adiponectin, HOMA-IR and quantitative insulin sensitivity check index (QUICKI) were significantly associated with NASH in univariate analysis, but overall predictivity of these parameters was low (AUC ROC = 0.62-0.68). In contrast, all patients with NASH with FS >= 2 had insulin resistance, as measured by QUICKI, and GH levels <0.45 ng/ml and all but one patient with NASH FS 2-3 had low DHEA levels (<123 MUg/dl). CONCLUSIONS: Low serum levels of GH and DHEA are very common in patients with NASH with more advanced fibrosis. Other biomarkers, including CK-18 fragment levels, have predictivity characteristics that would be of low clinical utility for distinguishing patients with normal histology or SS from those with NASH. These findings demonstrate an endocrine profile associated with advanced fibrosis. PMID- 22098615 TI - Severe hemorrhage because of delayed iliac vein rupture after dialysis catheter placement: is it preventable? AB - Mechanical complications of femoral catheterization for hemodialysis include pseudoaneurysm, arteriovenous fistulae, neurological injury, and vessel perforation. With regard to the latter, severe hemorrhage is a rare but devastating and potentially fatal complication. We report the case of a 76-year old female who underwent femoral catheterization for hemodialysis using ultrasound guidance. The first hemodialysis session was conducted without incident. Unfortunately, inadvertent injury and delayed perforation of the iliac vein resulted in severe hemorrhage and retroperitoneal hematoma. Surgical repair was performed. The patient was asymptomatic after the procedure and was discharged 15 days later. Based on this case and a review of the literature, we present mechanisms and ways to prevent this complication. PMID- 22098616 TI - Fracture susceptibility of endodontically treated teeth. AB - AIM: To assess the influence of cervical preparation on fracture susceptibility of roots. MATERIAL AND METHODS: During root canal instrumentation, the cervical portions were prepared with different taper instruments: I: no cervical preparation; II: #30/.08; III: #30/.10; IV: #70/.12. The specimens were sealed with the following filling materials (n = 8), A: unfilled; B: Endofill/gutta percha; C: AH Plus/gutta-percha; D: Epiphany SE/Resilon. For the fracture resistance test, a universal testing machine was used at 1 mm per minute. RESULTS: anova demonstrated difference (P < 0.05) between taper instruments with a higher value for group I (205.3 +/- 77.5 N) followed by II (185.2 +/- 70.8 N), III (164.8 +/- 48.9 N), and IV (156.7 +/- 41.4 N). There was no difference (P > 0.05) between filling materials A (189.1 +/- 66.3 N), B (186.3 +/- 61.0 N), C (159.7 +/- 69.9 N), and D (176.9 +/- 55.2 N). CONCLUSIONS: Greater cervical wear using a #70/.12 file increased the root fracture susceptibility, and the tested filling materials were not able to restore resistance. PMID- 22098617 TI - Genetic testing and screening of individuals at risk of NF2. AB - Genetic testing and management of the at-risk individual for neurofibromatosis type 2 (NF2) is complicated by the well-documented risk of mosaicism that causes a milder later onset more asymmetrical disease course. Risks of NF2 were derived from genetic testing of over 1000 individuals through the Manchester NF2-testing service. Individuals are at risk of NF2 or have 'potential' NF2 if they have features of the disease that fall short of diagnostic criteria or are the first degree relative of someone with NF2 or suspected NF2. The present protocol devised for the Nationally Commissioned Group (NCG) NF2 service in England addresses the risks, genetic testing and screening protocol for individuals at risk of NF2. Screening with cranial magnetic resonance imaging is advised until the risk of NF2 falls below a pragmatic threshold of 1%. Multiple case scenarios are shown to illustrate how to use the protocol. PMID- 22098618 TI - Cross-functional E3 ligases Parkin and C-terminus Hsp70-interacting protein in neurodegenerative disorders. AB - The study of neurodegenerative disorders has had a major impact on our understanding of more fundamental mechanisms underlying neurobiology. Breakthroughs in the genetics of Alzheimer's (AD) and Parkinson's diseases (PD) has resulted in new knowledge in the areas of axonal transport, energy metabolism, protein trafficking/clearance and synaptic physiology. The major neurodegenerative diseases have in common a regional or network pathology associated with abnormal protein accumulation(s) and various degrees of motor or cognitive decline. In AD, beta-amyloids are deposited in extracellular diffuse and compacted plaques as well as intracellularly. There is a major contribution to the disease by the co-existence of an intraneuronal tauopathy. Additionally, PD-like Lewy Bodies (LBs) bearing aggregated alpha-synuclein is present in 40-60% of all AD cases, especially involving amygdala. Amyloid deposits can be degraded or cleared by several mechanisms, including immune-mediated and transcytosis across the blood-brain barrier. Another avenue for disposal involves the lysosome pathway via autophagy. Enzymatic pathways include insulin degradative enzyme and neprilysin. Finally, the co-operative actions of C-terminus Hsp70 interacting protein (CHIP) and Parkin, components of a multiprotein E3 ubiquitin ligase complex, may be a portal to proteasome-mediated degradation. Mutations in the Parkin gene are the most common genetic link to autosomal recessive Parkinson's disease. Parkin catalyzes the post-translational modification of proteins with polyubiquitin, targeting them to the 26S proteasome. Parkin reduces intracellular Abeta(1-42) peptide levels, counteracts its effects on cell death, and reverses its effect to inhibit the proteasome. Additionally, Parkin has intrinsic cytoprotective activity to promote proteasome function and defend against oxidative stress to mitochondria. Parkin and CHIP are also active in amyloid clearance and cytoprotection in vivo. Parkin has cross-functionality in additional neurodegenerative diseases, for instance, to eliminate polyglutamine expanded proteins, reducing their aggregation and toxicity and reinstate proteasome function. The dual actions of CHIP (molecular co-chaperone and E3 ligase) and Parkin (as E3-ubiquitin ligase and anti-oxidant) may also play a role in suppressing inflammatory reactions in animal models of neurodegeneration. In this review, we focus on the significance of CHIP and Parkin as inducers of amyloid clearance, as cytoprotectants and in the suppression of reactive inflammation. A case is made for more effort to explore whether neurodegeneration associated with proteinopathies can be arrested at early stages by promoting their mutual action. PMID- 22098619 TI - Shifting species interactions in terrestrial dryland ecosystems under altered water availability and climate change. AB - Species interactions play key roles in linking the responses of populations, communities, and ecosystems to environmental change. For instance, species interactions are an important determinant of the complexity of changes in trophic biomass with variation in resources. Water resources are a major driver of terrestrial ecology and climate change is expected to greatly alter the distribution of this critical resource. While previous studies have documented strong effects of global environmental change on species interactions in general, responses can vary from region to region. Dryland ecosystems occupy more than one third of the Earth's land mass, are greatly affected by changes in water availability, and are predicted to be hotspots of climate change. Thus, it is imperative to understand the effects of environmental change on these globally significant ecosystems. Here, we review studies of the responses of population level plant-plant, plant-herbivore, and predator-prey interactions to changes in water availability in dryland environments in order to develop new hypotheses and predictions to guide future research. To help explain patterns of interaction outcomes, we developed a conceptual model that views interaction outcomes as shifting between (1) competition and facilitation (plant-plant), (2) herbivory, neutralism, or mutualism (plant-herbivore), or (3) neutralism and predation (predator-prey), as water availability crosses physiological, behavioural, or population-density thresholds. We link our conceptual model to hypothetical scenarios of current and future water availability to make testable predictions about the influence of changes in water availability on species interactions. We also examine potential implications of our conceptual model for the relative importance of top-down effects and the linearity of patterns of change in trophic biomass with changes in water availability. Finally, we highlight key research needs and some possible broader impacts of our findings. Overall, we hope to stimulate and guide future research that links changes in water availability to patterns of species interactions and the dynamics of populations and communities in dryland ecosystems. PMID- 22098620 TI - Changes in blood vessel maturation in the fibrous cap of the tumor rim. AB - It is widely accepted that blood vessels in the tumor microenvironment are immature because mural cell (MC) adhesion to endothelial cells (ECs) is broadly lacking. Hyperpermeability of the tumor vasculature then results in interstitial hypertension that mitigates against penetration of anticancer drugs into the depths of the tumor. It has been suggested that treatment with angiogenesis inhibitors normalizes blood vessels, resulting in restoration of normal permeability and improved drug delivery. However, recent reports suggest that cancer cell invasion is induced from the edge of the tumor into peripheral areas after treatment with angiogenesis inhibitors. Therefore, it is important to assess the status of blood vessels in the fibrous cap at the tumor rim after antiangiogenesis therapy. In the present study, we found that mature blood vessels in which ECs are covered with MCs are present in the fibrous cap. After treatment with angiogenesis inhibitors, immature blood vessels were destroyed and vascular function was significantly improved, but maturing blood vessels in which ECs were covered with MCs remained visible. These maturing blood vessels showed a less dilated character after treatment with the angiogenesis inhibitors. It is widely accepted that well-matured blood vessels are sheathed in extracellular matrix (ECM) and that cancer cells migrate along tracks made of ECM collagen fibers. Therefore, our data indicate the importance of destroying maturing blood vessels outside the tumor parenchyma to prevent cancer cell invasion. PMID- 22098621 TI - Phagocytic properties in tumor astrocytes. AB - In glioblastoma multiforme (GBM), the pathophysiological events preceding and promoting an uncontrolled and remarkable growth is largely unknown. Studies on gliomas and macrophage expression have shown high levels of phagocytic cells, that is, microglial cells. It has also been demonstrated that human astrocytic cells and rat glioma cells are capable of phagocytosis. The purpose of this study was to investigate a potential phagocytic property in human GBM cells in tumor biopsies from surgery. With an immunhistochemical double staining using macrophage markers (CD68 and CD163) and human telomerase reverse transcriptase (hTERT) as a marker for neoplastic cells, we found high levels of double positive cells in human GBM. In hematoxylin-erythrosin stained sections, we also identified fragmented cell components in the cytoplasm of tumor cells. In our judgement, many neoplastic cells in GBM are also positive for macrophage markers. We suggest that human astroglial tumor cells may have phagocytic properties or phagocyte-like properties. This may represent a latent capacity of self-defence, evoked under certain circumstances. It is likely that these properties substantially help the tumors thrive and expand. PMID- 22098622 TI - Thermodynamics of supramolecular naphthalenediimide nanotube formation: the influence of solvents, side chains, and guest templates. AB - Amino-acid functionalized naphthalenediimides self-assemble into hydrogen-bonded supramolecular helical nanotubes via a noncooperative, isodesmic process; the self-assembly of ordered helical systems is usually realized through a cooperative process. This unexpected behavior was rationalized as a manifestation of entropy-enthalpy compensation. Fundamental insights into the thermodynamics governing this self-assembly were obtained through the fitting of the isodesmic model to (1)H NMR spectrometry and circular dichroism spectroscopy measurements. Furthermore, we have extended the application of this mathematical model, for the first time, to quantitatively estimate the effect of guests, solvents, and side chains on the stability of the supramolecular nanotube; most significantly, we demonstrate that C(60) acts as a template to stabilize the nanotube assembly and thereby substantially increase the degree of polymerization. PMID- 22098623 TI - Gonadotrophin secretion pattern in anorchid boys from birth to pubertal age: pathophysiological aspects and diagnostic usefulness. AB - CONTEXT: The biphasic ontogeny of serum gonadotrophins observed in normal children also exists in girls with gonadal dysgenesis, although with higher levels. However, limited data exist in prepubertal boys with anorchia. OBJECTIVE: To investigate whether the existence of testicular tissue is required for gonadotrophin downregulation in boys. Secondarily, we analysed the prevalence of high gonadotrophins and its diagnostic value to assess the presence or absence of testes in childhood. STUDY DESIGN: In a retrospective, semi-longitudinal study, we compared serum gonadotrophin levels in 35 boys with anorchia aged 0-18 years, in 29 bilaterally cryptorchid boys with abdominal testes and in 236 normal boys. RESULTS: In anorchid boys, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were abnormally high in the first months after birth, then decreased progressively. LH decreased more readily than FSH and dropped to normal values in up to 70% of anorchid patients before the usual age of pubertal onset, when both gonadotrophins increased again to very high levels. In cryptorchid boys, FSH was elevated in a significantly (P < 0.0001) lower proportion of cases. Below the age of 6 years, FSH below 2 IU/l ruled out anorchia and LH above 5 IU/l confirmed anorchia with high accuracy. Between 6 and 11 years, FSH or LH levels above 5 IU/l were highly specific for the absence of testes. CONCLUSIONS: The U-shaped pattern of serum gonadotrophins observed in normal males from birth to puberty was also found in anorchid boys, but with gonadotrophin levels considerably elevated. Serum gonadotrophin levels may normalize in anorchid boys during late childhood only to rise again at puberty. The presence of testicular tissue results in restrain of gonadotrophin secretion in most patients, even if the testes are cryptorchid. PMID- 22098624 TI - SOX4 interacts with plakoglobin in a Wnt3a-dependent manner in prostate cancer cells. AB - BACKGROUND: SOX4 is a developmental transcription factor that is required for differentiation and proliferation in multiple tissues. SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is still not well understood. Thus, the identification of additional SOX4 binding partners is essential for elucidating the mechanism of SOX4-mediated effects in cancer progression. RESULTS: Here, we have adapted a one-step affinity purification method that enables rapid purification of SOX4 complexes via intracellular biotinylation of the amino-terminus of SOX4 to perform large-scale proteomics analysis. We have discovered that junction plakoglobin (JUP) interacts with SOX4 in both the cytosol and the nucleus and the interaction between SOX4 and plakoglobin is significantly increased when prostate and breast cancer cells are stimulated with WNT3A. Interactions between SOX4 and plakoglobin were further enhanced by the nuclear export inhibitor leptomycin B (LMB), suggesting that plakoglobin promotes nuclear export of SOX4. The SOX4-plakoglobin complex affected the expression of Wnt pathway target genes and SOX4 downstream targets, such as AXIN2, DICER1, and DHX9. In addition, SOX4 DNA binding activity to the promoters of DICER1, AXIN2, DHX9 and SOX4 itself was reduced by conditions that promote SOX4-plakoglobin complex formation. Conditions that enhanced SOX4 plakoglobin interactions resulted in reduced transcriptional activity of beta catenin luciferase reporters. CONCLUSIONS: These data suggest that this newly identified interaction between SOX4 and plakoglobin is inhibitory and provides new insights into the role of SOX4 in key pathways in cell proliferation, development, and cancer progression. PMID- 22098625 TI - What works to meet the sexual and reproductive health needs of women living with HIV/AIDS. AB - It is critical to include a sexual and reproductive health lens in HIV programming as most HIV transmission occurs through sexual intercourse. As global attention is focusing on the sexual and reproductive health needs of women living with HIV, identifying which interventions work becomes vitally important. What evidence exists to support sexual and reproductive health programming related to HIV programmes?This article reviews the evidence of what works to meet the sexual and reproductive health needs of women living with HIV in developing countries and includes 35 studies and evaluations of eight general interventions using various methods of implementation science from 15 countries. Data are primarily from 2000-2009. Searches to identify effective evaluations used SCOPUS, Popline, Medline, websites and consultations with experts. Evidence was ranked using the Gray Scale.A range of successful and promising interventions to improve the sexual and reproductive health and rights of women living with HIV include: providing contraceptives and family planning counselling as part of HIV services; ensuring early postpartum visits providing family planning and HIV information and services; providing youth-friendly services; supporting information and skills building; supporting disclosure; providing cervical cancer screening; and promoting condom use for dual protection against pregnancy and HIV. Provision of antiretrovirals can also increase protective behaviours, including condom use.While many gaps in programming and research remain, much can be done now to operationalize evidence-based effective interventions to meet the sexual and reproductive health needs of women living with HIV. PMID- 22098626 TI - Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles. AB - BACKGROUND: Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. METHODS: Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD(50)) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. RESULTS: After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. CONCLUSIONS: The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity. PMID- 22098627 TI - Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and aetiology of cirrhosis and predicts prognosis. AB - BACKGROUND: Inflammation is a major factor for the progression of chronic liver diseases. Interactions between urokinase plasminogen activator (uPA) and its receptor (uPAR) have been functionally linked to hepatic inflammation and fibrosis in mice. High serum concentrations of soluble uPAR (suPAR) are suggested to reflect activated immune cells. AIMS: We evaluated suPAR serum levels as a diagnostic and prognostic biomarker in patients with chronic liver diseases. METHODS: Prospective, cross-sectional cohort study of 159 patients with chronic liver diseases (61 without, 98 with established cirrhosis) and 43 healthy controls. Transplant-free survival was monitored for up to 3 years. RESULTS: Soluble urokinase plasminogen activator serum concentrations were significantly elevated in patients with chronic liver diseases compared with controls. Cirrhotic patients displayed higher levels than non-cirrhotics, closely depending on stage of fibrosis or cirrhosis. suPAR levels had high diagnostic power to identify established cirrhosis in chronic liver diseases. Circulating suPAR closely correlated with liver function, fibrosis markers, but also with systemic inflammation and renal function. A distinct suPAR elevation was noticed in patients with alcoholic aetiology of liver disease. suPAR identified alcoholic origin more precisely compared with classical indicators of alcoholism (mean corpuscular volume, gamma glutamyl transpeptidase). Strikingly, elevated suPAR levels were identified as a strong predictor of mortality or need for transplantation. suPAR levels >9 ng/ml indicated adverse prognosis (sensitivity: 70.7%, specificity: 77.8%, relative risk: 8.5; 95% confidence interval: 3.5 20.3). CONCLUSIONS: Serum suPAR is a potential novel biomarker for the diagnosis of cirrhosis, identification of alcoholic origin and for determining prognosis in patients with chronic liver disease. PMID- 22098628 TI - Illness burden and medical comorbidity in the Systematic Treatment Enhancement Program for Bipolar Disorder. AB - OBJECTIVE: Coexisting chronic medical conditions are common in bipolar disorder. Here, we report the prevalence and correlates of medical comorbidity in patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). We were particularly interested in associations between variables reflecting illness chronicity and burden with comorbid medical conditions. METHOD: We used intake data from the open-label component of the STEP-BD. History of medical comorbidity was obtained from the affective disorders evaluation, and its presence was the outcome of interest. The sample size in analyses varied from 3399 to 3534. We used multiple Poisson regression to obtain prevalence ratios. RESULTS: The prevalence of any medical comorbidity in the sample was 58.8%. In addition to demographic variable, several clinical characteristics were associated with the frequency of medical comorbidity. Having more than 10 previous mood episodes, childhood onset, smoking, lifetime comorbidity with anxiety, and substance use disorders were independently associated with having a medical comorbidity in the final multivariate model. CONCLUSION: The results presented here reveal strong associations between variables related to illness chronicity and medical burden in bipolar disorder. This lends further support to recent multidimensional models incorporating medical morbidity as a core feature of bipolar disorder. PMID- 22098629 TI - Development of a 'toolkit' to identify medical students at risk of failure to thrive on the course: an exploratory retrospective case study. AB - BACKGROUND: An earlier study at Nottingham suggested that 10-15% of the medical student intake was likely to fail completely or have substantial problems on the course. This is a problem for the students, the Faculty, and society as a whole. If struggling students could be identified early in the course and additional pastoral resources offered, some of this wastage might be avoided. An exploratory case study was conducted to determine whether there were common indicators in the early years, over and above academic failure, that might aid the identification of students potentially at risk. METHODS: The study group was drawn from five successive cohorts. Students who had experienced difficulties were identified in any of four ways: from Minutes of the Academic Progress Committee; by scanning examination lists at key stages (end of the first two years, and finals at the end of the clinical course); from lists of students flagged to the Postgraduate Deanery as in need of extra monitoring or support; and from progress files of those who had left the course prematurely. Relevant data were extracted from each student's course progress file into a customised database. RESULTS: 1188 students were admitted over the five years. 162 (14%) were identified for the study, 75 of whom had failed to complete the course by October 2010. In the 87 who did graduate, a combination of markers in Years 1 and 2 identified over half of those who would subsequently have the most severe problems throughout the course. This 'toolkit' comprised failure of 3 or more examinations per year, an overall average of <50%, health or social difficulties, failure to complete Hepatitis B vaccination on time, and remarks noted about poor attitude or behaviour. CONCLUSIONS: A simple toolkit of academic and non-academic markers could be used routinely to help identify potential strugglers at an early stage, enabling additional support and guidance to be given to these students. PMID- 22098630 TI - Clinical outcomes of endoscopic submucosal dissection and endoscopic mucosal resection for laterally spreading tumors larger than 20 mm. AB - BACKGROUND AND AIMS: Colorectal laterally spreading tumors (LST) > 20 mm are usually treated by endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR). Endoscopic piecemeal mucosal resection (EPMR) is sometimes required. The aim of our study was to compare the outcomes of ESD and EMR, including EPMR, for such LST. METHODS: A total of 269 consecutive patients with a colorectal LST > 20 mm were treated endoscopically at our hospital from April 2006 to December 2009. We retrospectively evaluated the complications and local recurrence rates associated with ESD, hybrid ESD (ESD with EMR), EMR, and EPMR. RESULTS: ESD and EMR were performed successfully for 89 and 178 LST, respectively: 61 by ESD; 28 by hybrid ESD; 70 by EMR; and 108 by EPMR. Between group differences in perforation rates were not significant. Local recurrence rates in cases with curative resection were as follows: 0% (0/56) in ESD; 0% (0/27) in hybrid ESD; 1.4% (1/69) in EMR; and 12.1% (13/107) in EPMR; that is, significantly higher in EPMR. No metastasis was seen at follow up. The recurrence rate for EPMR yielding >= three pieces was significantly high (P < 0.001). All 14 local recurrent lesions were adenomas that were cured endoscopically. CONCLUSIONS: As for safety, ESD/hybrid ESD is equivalent to EMR/EPMR. ESD/hybrid ESD is a feasible technique for en bloc resection and showed no local recurrence. Although local recurrences associated with EMR/EPMR were seen, which were conducted based on our indication criteria, all local recurrences could obtain complete cure by additional endoscopic treatment. PMID- 22098632 TI - Preparation of phosphate-enriched hemodialysates. PMID- 22098631 TI - Unique somato-dendritic distribution pattern of Kv4.2 channels on hippocampal CA1 pyramidal cells. AB - A-type K(+) current (I(A)) plays a critical role in controlling the excitability of pyramidal cell (PC) dendrites. In vitro dendritic patch-pipette recordings have demonstrated a prominent, sixfold increase in I(A) density along the main apical dendrites of rat hippocampal CA1 PCs. In these cells, I(A) is mediated by Kv4.2 subunits, whose precise subcellular distribution and densities in small diameter oblique dendrites and dendritic spines are still unknown. Here we examined the densities of the Kv4.2 subunit in 13 axo-somato-dendritic compartments of CA1 PCs using a highly sensitive, high-resolution quantitative immunogold localization method (sodium dodecyl sulphate-digested freeze-fracture replica-labelling). Only an approximately 70% increase in Kv4.2 immunogold density was observed along the proximo-distal axis of main apical dendrites in the stratum radiatum with a slight decrease in density in stratum lacunosum moleculare. A similar pattern was detected for all dendritic compartments, including main apical dendrites, small-diameter oblique dendrites and dendritic spines. The specificity of the somato-dendritic labelling was confirmed in Kv4.2( /-) tissue. No specific immunolabelling for the Kv4.2 subunit was found in SNAP 25-containing presynaptic axons. Our results demonstrate a novel distribution pattern of a voltage-gated ion channel along the somato-dendritic surface of CA1 PCs, and suggest that the increase in the I(A) along the proximo-distal axis of PC dendrites cannot be solely explained by a corresponding increase in Kv4.2 channel number. PMID- 22098633 TI - Pilotin-secretin recognition in the type II secretion system of Klebsiella oxytoca. AB - A crucial aspect of the functionality of bacterial type II secretion systems is the targeting and assembly of the outer membrane secretin. In the Klebsiella oxytoca type II secretion system, the lipoprotein PulS, a pilotin, targets secretin PulD monomers through the periplasm to the outer membrane. We present the crystal structure of PulS, an all-helical bundle that is structurally distinct from proteins with similar functions. Replacement of valine at position 42 in a charged groove of PulS abolished complex formation between a non lipidated variant of PulS and a peptide corresponding to the unfolded region of PulD to which PulS binds (the S-domain), in vitro, as well as PulS function in vivo. Substitutions of other residues in the groove also diminished the interaction with the S-domain in vitro but exerted less marked effects in vivo. We propose that the interaction between PulS and the S-domain is maintained through a structural adaptation of the two proteins that could be influenced by cis factors such as the fatty acyl groups on PulS, as well as periplasmic trans acting factors, which represents a possible paradigm for chaperone-target protein interactions. PMID- 22098634 TI - Lapses in safety in end-stage renal disease patients admitted to surgical services. AB - Chronic dialysis patients are a vulnerable population that may be highly susceptible to medical errors, particularly when they are hospitalized. We performed a chart review of chronic hemodialysis patients admitted to surgical services at a tertiary care center in order to characterize lapses in patient safety. We conducted a retrospective chart review of admissions of patients receiving chronic hemodialysis to various surgical services at St. Michael's Hospital from January 1, 2009 to December 31, 2010. For each hospitalization, we collected data on four process of care indicators of potential safety lapses. When these lapses were identified, we sought to determine whether: (i) the lapse was detected and remedied; and (ii) the lapse resulted in an adverse event. Among the 41 patients, 96 process of care lapses were identified. Multiple lapses were detected in 83% of the cohort. Failure to order a renal diet (72%) occurred most often. There was one adverse event. Process of care lapses were detected 39% of the time, usually within 1.5 days of their occurrence. Patients receiving chronic hemodialysis admitted to surgical services experience multiple lapses in patient safety, which often remain undetected. As such, it is imperative that these patients be closely monitored in order to mitigate against potential adverse events. PMID- 22098636 TI - Transition-metal-catalyzed uninterrupted four-step sequence to access trisubstituted isoxazoles. AB - We describe herein a novel uninterrupted four-step sequence to access trisubstituted isoxazoles from readily available propargylic alcohols using sequentially iron and palladium catalytic systems. The advantages of such a strategy are illustrated by the high overall yields and the time-saving procedure that are reported. PMID- 22098635 TI - Changes in vitamin D binding protein and vitamin D concentrations associated with liver transplantation. AB - BACKGROUND: Vitamin D deficiency is associated with fractures, infections and death. Liver disease impairs vitamin D and vitamin D binding protein (DBP) metabolism. AIMS: We aimed to determine the impact of liver transplantation on vitamin D, particularly on DBP and free vitamin D concentrations. METHODS: Serum 25(OH)D, 1,25(OH)(2) D and DBP concentrations were measured in 202 adults before liver transplantation and 3 months later in 155. Free vitamin D concentrations were estimated from these values. Risk factors for 25(OH)D deficiency (<20 ng/ml) and low 1,25(OH)(2) D (<20 pg/ml) were examined with logistic regression, and changes in concentrations following transplantation with linear regression. RESULTS: Pretransplant, 84% were 25(OH)D deficient, 13% had 25(OH)D concentrations <2.5 ng/ml, and 77% had low 1,25(OH)(2) D. Model for end-stage liver disease score >= 20 (P < 0.005) and hypoalbuminemia (P < 0.005) were associated with low 25(OH)D and 1,25(OH)(2) D concentrations. Following transplantation, 25(OH)D concentrations increased a median of 17.8 ng/ml (P < 0.001). Albumin increased from a median of 2.7 to 3.8 g/dl (P < 0.001) and DBP from 8.6 to 23.8 mg/dl (P < 0.001). Changes in total 25(OH)D were positively and independently associated with changes in DBP (P < 0.05) and albumin (P < 0.001). Free 25(OH)D concentrations rose from 6.0 to 9.7 pg/ml (P < 0.001). In contrast, total 1,25(OH)(2)D concentrations rose only by 4.3 pg/ml (P < 0.001) and free 1,25(OH)(2D concentrations declined (P < 0.001). CONCLUSIONS: Serum total and free 25(OH)D and DBP concentrations rose substantially following transplantation, while 1,25(OH)(2) D concentrations showed modest changes and free 1,25(OH)(2) D decreased. Studies of the effects of vitamin D status on diverse transplant complications are needed. PMID- 22098637 TI - Pharmacokinetic interaction of intramammary ceftriaxone and oral polyherbal drug (Fibrosin((r))) in goats. AB - BACKGROUND: The aim of the present study was to determine pharmacokinetic interaction of ceftriaxone and polyherbal drug (Fibrosin((r))) in lactating goats following single dose intramammary administration of ceftriaxone with 1 h pre single dose oral administration of Fibrosin((r)). METHODS: Pharmacokinetic interaction of ceftriaxone and Fibrosin((r)) was evaluated in lactating goats following single dose intramammary administration of ceftriaxone at 50 mg/kg with 1 h pre-single dose oral administration of Fibrosin((r)) (1.9 g). Estimation of ceftriaxone and its metabolite, ceftizoxime, was determined by high performance liquid chromatography. RESULTS: Fibrosin((r)) treated goats showed a typical absorption-reabsorption phase of ceftriaxone in plasma following intramammary administration. Neither ceftriaxone nor ceftizoxime was detected in the plasma and urine of goats without Fibrosin((r)) treatment, however, ceftriaxone persisted for 36 h and ceftizoxime was present from 48 h to 72 h in the plasma of Fibrosin((r)) treated goats. Ceftizoxime was also available from 72 h to 360 h post-dosing in milk in the presence of Fibrosin((r)) following intramammary administration of ceftriaxone suggesting the polyherbal drug played a major role in the penetration of ceftriaxone from milk to systemic circulation. Furthermore, the polyherbal drug increased the bioavailability of ceftizoxime in milk following the metabolism of ceftriaxone. CONCLUSIONS: Polyherbal drug (Fibrosin((r))) plays a major role in the penetration of ceftriaxone from milk to systemic circulation and may be responsible for increased bioavailability of its metabolite in the mammary gland resulting in higher concentration and longer persistence of the drug in milk. PMID- 22098638 TI - Protein hydrolysates and tissue repair. AB - Protein hydrolysates provide a rich source of protein which is useful in situations where excess protein is needed, such as during repair of tissue damage. The consumption of protein hydrolysates has been shown to result in more rapid uptake of amino acids compared with whole proteins or free-form amino acid mixtures and some peptides in hydrolysates exhibit biological activity. Early studies showed that protein hydrolysates are more effectively utilised than intact proteins or amino acids. In addition, they promote a strong insulinotropic effect, which reduces protein breakdown and enhances muscle and tissue uptake of branched-chain amino acids. These effects contribute to benefits of protein hydrolysates for enhancing repair of tissue damage caused by surgery, ulcers, burns and muscle-damaging exercise. While there is evidence that protein hydrolysates may be useful for facilitating tissue repair, additional research is needed to further examine various roles of protein hydrolysates in this process. PMID- 22098642 TI - Viscous friction of hydrogen-bonded matter. AB - Amontons' law successfully describes friction between macroscopic solid bodies for a wide range of velocities and normal forces. For the diffusion and forced sliding of adhering or entangled macromolecules, proteins, and biological complexes, temperature effects are invariably important, and a similarly successful friction law at biological length and velocity scales is missing. Hydrogen bonds (HBs) are key to the specific binding of biomatter. Here we show that friction between hydrogen-bonded matter obeys in the biologically relevant low-velocity viscous regime a simple law: the friction force is proportional to the number of HBs, the sliding velocity, and a friction coefficient gamma(HB). This law is deduced from atomistic molecular dynamics simulations for short peptide chains that are laterally pulled over planar hydroxylated substrates in the presence of water and holds for widely different peptides, surface polarities, and applied normal forces. The value of gamma(HB) is extrapolated from simulations at sliding velocities in the range from V = 10(-2) to 100 m/s by mapping on a simple stochastic model and turns out to be of the order of gamma(HB) ? 10(-8) kg/s. The friction of a single HB thus amounts to the Stokes friction of a sphere with an equivalent radius of roughly 1 MUm moving in water. Cooperativity is pronounced: roughly three HBs act collectively. PMID- 22098643 TI - [Emergencies in ENT imaging]. PMID- 22098644 TI - [Imaging features of temporal bone fractures]. AB - Imaging evaluation of the temporal bone often is neglected at the acute phase in patients with head trauma due to the urgent need to evaluate the brain. It should nonetheless be an integral part of this evaluation by the addition of thin dedicated CT images. Knowledge of the mechanisms of traumatic injuries combined to multiplanar reconstructions of the acquisition volume lead to accurate depiction of temporal bone injuries, including lesions of ossicles and footplate, structures measuring 2 or 3 mm. This comprehensive work-up will then allow prompt optimal ENT management and may improve the functional outcome. PMID- 22098645 TI - [Sudden onset hearing loss: imaging work-up]. AB - Sudden onset hearing loss is idiopathic. It occurs in less than 24 h and spontaneously resolves within 15 days in two thirds of cases. Imaging is performed to exclude other causes of sudden onset hearing loss (vestibular schwannoma, vertebral artery dissection, stroke) and evaluate the inner ear structures. A few anatomical anomalies have been associated with an increased risk of hearing loss. Morphological anomalies involved the following structures in decreasing order of frequency: lateral semicircular canal (hypoplasia and dilatation), superior semicircular canal, posterior semicircular canal, vestibule and cochlea. Enlargement of the vestibular aqueduct also is frequently observed. PMID- 22098646 TI - [Sudden onset vertigo: imaging work-up]. AB - Vertigo and dysequilibrium are a frequent cause of medical consultation. Clinical evaluation is essential. Some cases of vertigo are diagnosed clinically while others require imaging, sometimes emergently (suspected stroke). MRI is the imaging modality of choice to assess the labyrinth (labyrinthitis? labyrinthine hemorrhage?), internal auditory canal (vestibular schwannoma? other tumor?...) and brain parenchyma including all structures of the auditory pathways: vestibular nuclei, vestibulocerebellar tract, tracts involved with ocular motricity, vestibular cortex... Multiple central etiologies exist: stroke, multiple sclerosis, tumor... However, some etiologies are best depicted with CT, especially lesions of the labyrinth: cholesteatoma, trauma, suspected dehiscence of the superior semicircular canal, suspected labyrinthine fistula... Finally, imaging may be negative (Benign Paroxysmal Positional Vertigo, Meniere's disease, vestibular neuritis, migraine...), merely reducing the differential diagnosis. PMID- 22098647 TI - [Skull base osteomyelitis]. AB - Skull base osteomyelitis is a rare but serious infection. It typically afflicts immunosuppressed patients and should be suspected in patients with persistent otitis complicated by cranial nerve palsy (VII, IX and XII). The most frequent germ is pseudomonas aeruginosa. Contiguous spread of infection occurs along neurovascular structures and weaker regions of the skull base, then into the soft tissue compartments of the face and nasopharynx. Diagnosis and treatment should be made early for this disease with poor prognosis and high mortality. PMID- 22098648 TI - [Intracranial complications from ENT infections]. AB - Sinonasal and temporal bone infections may extend to the skull, skull base, meninges, pericerebral spaces, brain parenchyma, dural sinuses, deep cerebral or cortical veins, intracranial arteries and cranial nerves either via contiguous or hematogeneous spread. The site of infection dictates the sites of potential complications: orbital with ethmoid sinusitis, cavernous sinus thrombophlebitis and oculomotor palsies with sphenoid sinusitis, transverse sinus thrombophlebitis with mastoiditis and superior sagittal sinus thrombophlebitis with frontal sinusitis. All may result in brain abscess. Congenital and acquired defects of the skull and meninges, with or without associated meningocele or meningoencephalocele, perilymphatic fistulas, and some anomalies of the inner ear may predispose to the intracranial extension of ENT infections. PMID- 22098649 TI - [Imaging evaluation of head and neck infections]. AB - Infections of the head and neck are frequent and usually have a good prognosis even though complications may sometimes be life threatening. In addition to airway compromise, intracranial and thoracic extension may occur. Diagnosis usually is made on clinical examination and imaging may play a significant role in assessing the extent of the disease, detecting complications and assist in surgical planning. The imaging protocol should be appropriate for the proposed diagnosis and suspected complications. CT of the soft tissues of the neck and chest is the imaging test of choice. Interpretation requires knowledge of the anatomy to understand the modalities of local and distant spread of the disease. Imaging evaluation is important but should not delay emergently needed treatment for entities such as epiglottitis and necrotizing fasciitis. PMID- 22098650 TI - [Complications from sinonasal surgery]. AB - Endoscopic sinonasal surgery is the main procedure in sinonasal pathology. Complications are rare but potentially severe given the close relationship between the nasal cavities and sinuses and the orbit, skull base and carotid arteries. The different types of surgeries along with the mechanisms of injury, presenting signs and symptoms, and imaging features of the different surgical complications will be reviewed. We will also review the anatomical variants increasing the surgical risk that radiologists should describe on preoperative imaging studies. PMID- 22098651 TI - [Vascular emergencies of the head and neck]. AB - The clinical manifestations of vascular lesions of the head and neck may be variable (hemorrhagic, ischemic, compressive). Diagnosis often is made at the time of acute presentation, but delayed manifestations, sometimes long after the initial presentation, should not be overlooked. Hemorrhagic manifestations are characterized by epistaxis, corresponding mainly to lesions of the nasal cavities but involvement of the internal carotid artery should be excluded (life threatening). In addition, some vascular malformations may lead to severe hemorrhage. Ischemic manifestations typically result from arterial dissection. A venous origin is also possible. Carotid-cavernous fistulas rarely lead to hemorrhagic or ischemic manifestations and tend to result in ocular manifestations, typically delayed and sometimes misleading. PMID- 22098652 TI - Monitoring intravesical pressure during gastroschisis closure. Does it help to decide between delayed primary or staged closure? AB - INTRODUCTION AND OBJECTIVE: Correction of gastroschisis may be accomplished by either primary or staged closure or even delayed primary closure after the use of a preformed silo. However, there is neither a consensus on the best approach nor established criteria to favor one method over the other. The aim of this paper was to investigate the role of intravesical pressure (IVP) as a tool to prevent abdominal compartment syndrome in newborns undergoing correction of abdominal wall defects. METHODS: We retrospectively analyzed 45 newborns with gastroschisis in whom trans-operative intravesical pressure was used to choose between primary or staged closure. A threshold of 20 cm H(2)O was used and the outcomes between the two methods were compared. RESULTS: In 24 children delayed primary closure was achieved while the remaining 21 underwent staged reduction and closure. There was no difference in the frequency of complications, time to begin oral feeding, length of parenteral nutrition or length of hospital stay between the children of the two groups. The incidence of temporary oliguria or anuria, averaged 33% and it was similar in both groups of children. CONCLUSION: The data here presented suggests that monitoring intraoperative IVP during correction of gastroschisis may help to select children in whom staged closure is necessary, keeping their complication rate and overall outcome similar to that of children undergoing delayed primary closure. Further prospective studies should investigate more deeply the correlation between type of closure and the development of a compartment syndrome. PMID- 22098653 TI - Primary lateral sclerosis: upper-motor-predominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration--immunohistochemical and biochemical analyses of TDP-43. AB - Primary lateral sclerosis (PLS) is clinically defined as a disorder selectively affecting the upper motor neuron (UMN) system. However, recently it has also been considered that PLS is heterogeneous in its clinical presentation. To elucidate the association of PLS, or disorders mimicking PLS, with 43-kDa TAR DNA-binding protein (TDP-43) abnormality, we examined two adult patients with motor neuron disease, which clinically was limited almost entirely to the UMN system, and was followed by progressive frontotemporal atrophy. In the present study, the distribution and severity, and biochemical profile of phosphorylated TDP-43 (pTDP 43) in the brains and spinal cords were examined immunohistochemically and biochemically. Pathologically, in both cases, frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U) was evident, with the most severe degeneration in the motor cortex. An important feature in both cases was the presence of Bunina bodies and/or ubiquitin inclusions, albeit very rarely, in the well preserved lower motor neurons. The amygdala and neostriatum were also affected. pTDP-43 immunohistochemistry revealed the presence of many positively stained neuronal cytoplamic inclusions (NCIs) and dystrophic neurites/neuropil threads in the affected frontotemporal cortex and subcortical gray matter. By contrast, such pTDP-43 lesions, including NCIs, were observed in only a few lower motor neurons. pTDP-43 immunoblotting revealed that fragments of ~25-kDa were present in the cortices, but not in the spinal cord in both cases. Genetically, neither of the patients had any mutation in the TDP-43 gene. In conclusion, we consider that although PLS may be a clinically significant disease entity, at autopsy, the majority of such clinical cases would present as upper-motor-predominant amyotrophic lateral sclerosis with FTLD-TDP. PMID- 22098654 TI - Quality in CKD: the 3 "Cs". PMID- 22098655 TI - Collegiality and CKD. PMID- 22098656 TI - Why work together? Developing effective comanagement strategies for the care of patients with CKD. AB - The ever-growing population of patients with CKD has prompted an increasing emphasis on earlier identification and proactive management by primary care providers. The provision of effective CKD care will necessitate a collegial relationship between the primary care providers and nephrologists exists. In this paper, barriers to the development of this working relationship, potential solutions within existing practice patterns, and newer ideas for effective communication will be explored. PMID- 22098657 TI - Complications of progression of CKD. AB - CKD is a complex comorbid condition with multiple manifestations. It is closely linked with cardiovascular disease and has a very high mortality rate. Currently, it consumes 28% of Medicare expenditures. Complications of CKD include hypertension, diabetes, dyslipidemia, cardiovascular disease, anemia, and bone and mineral disorders. It is underrecognized and underdiagnosed in primary care offices. There is strong evidence that controlling blood pressure, blood glucose, and use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in albuminuric patients, as well as referral to the nephrologist when glomerular filtration rate is <30 mL/min/1.73 m(2), is associated with lower mortality, better access to kidney transplantation, improved management of comorbidities, and less frequent use of catheters for dialysis and to lower mortality. PMID- 22098658 TI - Improving blood pressure control among adults with CKD and diabetes: provider focused quality improvement using electronic health records. AB - Current evidence demonstrates poor provider knowledge and compliance to clinical practice guidelines (CPGs) for CKD screening, blood pressure (BP) goals specific to people with diabetes mellitus (DM) and CKD, and underutilization or incorrect drug selection for antihypertensive therapy. This 12-week provider-focused quality improvement project sought to (1) increase primary care provider (PCP) adherence to CPG in the treatment and control of BP among adults with CKD and DM by using electronic health records (EHRs) and patient-level feedback (scorecards); (2) increase PCP delivery of basic CKD patient education by using EHR-based decision support; and (3) assess whether electronic decision support and scorecards changed provider behavior. The project included 46 PCPs, physicians, and nurse practitioners, in a statewide federally qualified health center that operates 12 comprehensive primary care sites in Connecticut. There were 6781 DM visits, among 3137 unique, racially diverse patients. There was a statistically significant increase in CKD screening, diagnosis, and use of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker. There was a statistically, but not clinically, significant increase in CKD basic education and ancillary service provider use when the provider was aware of the diagnosis or used EHR enhancements. EHR decision support and real-time provider feedback are necessary but not sufficient to improve uptake of CPG and to change PCP behavior. PMID- 22098659 TI - Geriatric nephrology: a paradigm shift in the approach to renal replacement therapy. AB - The population of elderly individuals diagnosed with CKD continues to grow. Many have multiple comorbid conditions that will impact life expectancy as well as decisions about whether to pursue renal replacement therapy. Nephrologists are uniquely positioned to assist their patients and caregivers in this regard and spend considerable time counseling them about the benefits and risks associated with dialysis therapy. This article presents an overview of many of the issues facing nephrologists, and provides tools to assist busy clinicians in helping their elderly patients in deciding whether to consider dialysis or intensive, nondialysis care. PMID- 22098660 TI - Referral and comanagement of the patient with CKD. AB - CKD is a common condition with well-documented associated morbidity and mortality. Given the substantial disease burden of CKD and the cost of ESRD, interventions to delay progression and decrease comorbidity remain an important part of CKD care. Early referral to nephrologists has been shown to delay progression of CKD. Conversely, late referral has been associated with increased hospitalizations, higher mortality, and worsened secondary outcomes. Late referral to nephrology has been consequent to numerous factors, including the health care system, provider issues, and patient related factors. In addition to timely referral to nephrologists, the optimal modality to provide care for CKD patients has also been evaluated. Multidisciplinary clinics have shown significant improvements in other disease states. Data for the use of these clinics have shown benefit in mortality, progression, and laboratory markers of disease severity. However, studies supporting the use of multidisciplinary clinics in CKD have been mixed. Evidence-based guidelines from groups, including Renal Physicians Association and NKF, provide tools for management of CKD patients by both generalists and nephrologists. Through the use of guidelines, timely referral, and a multidisciplinary approach to care, the ability to provide effective and efficient care for CKD patients can be improved. We present a model to guide a multidisciplinary comanagement approach to providing care to patients with CKD. PMID- 22098661 TI - Peritoneal dialysis versus hemodialysis: risks, benefits, and access issues. AB - Peritoneal dialysis (PD) and hemodialysis (HD) are dialysis options for end-stage renal disease patients in whom preemptive kidney transplantation is not possible. The selection of PD or HD will usually be based on patient motivation, desire, geographic distance from an HD unit, physician and/or nurse bias, and patient education. Unfortunately, many patients are not educated on PD before beginning dialysis. Most studies show that the relative risk of death in patients on in center HD versus PD changes over time with a lower risk on PD, especially in the first 3 months of dialysis. The survival advantage of PD continues for 1.5-2 years but, over time, the risk of death with PD equals or becomes greater than with in-center HD, depending on patient factors. Thus, PD survival is best at the start of dialysis. Patient satisfaction may be higher with PD, and PD costs are significantly lower than HD costs. The new reimbursement system, including bundling of dialysis services, may lead to an increase in the number of incident patients on PD. The high technique failure of PD persists, despite significant reductions in peritonitis rates. Infection also continues to be an important cause of mortality and morbidity among HD patients, especially those using a central venous catheter as HD access. Nephrologists' efforts should be focused on educating themselves and their patients about the opportunities for home modality therapies and reducing the reliance on central venous catheter for long-term HD access. PMID- 22098662 TI - Transplantation and the primary care physician. AB - Increasing appreciation of the survival benefits of kidney transplantation, compared with chronic dialysis, has resulted in more patients with kidney disease being referred and receiving organs. The evolving disparity between a rapidly increasing pool of candidates and a smaller pool of available donors has created new issues for the physicians who care for kidney patients and their potential living donors. This article outlines current efforts to address the growing number of patients who await transplantation, including relaxation of traditional donation criteria, maximization of living donation, and donation schemas that permit incompatible donor-recipient pairs to participate through paired donation and transplantation chains. New ethical issues faced by donors and recipients are discussed. Surgical advances that reduce the morbidity of donors are also described, as is the role of the primary physician in medical issues of both donors and recipients. PMID- 22098663 TI - From CKD to ESRD: a tale of two transitions. AB - Transitions in levels of health offer important opportunities to affect patient outcomes. The transition from CKD to ESRD and dialysis dependence is costly in personal, social, and economic terms. This paper reviews these costs and offers resources that can be used by physicians and medical teams to help patients and their families weather the challenges of this process. PMID- 22098664 TI - The "no dialysis" option. AB - Increasing numbers of patients are starting dialysis who have limited prognoses for 6-month survival. The presence of multiple comorbidities, aging, and frailty contributes to this phenomenon. The rate of dialysis withdrawal has been accelerating over the past decade, and this calls into question the condition of patients who are initiating dialysis. One option is to consider and discuss the "no dialysis" option with patients and family. Patients need to be identified who may benefit from this option, and their medical management needs to be reviewed. PMID- 22098665 TI - The patient-centered medical home and the nephrologist. AB - The patient-centered medical home (PCMH) is a model of practice that has been proposed to address the many ills of our current health care delivery and financing systems. At its heart is a primary care practice that provides comprehensive, coordinated, high-quality, personalized care. Integral to the success of the PCMH model is a "neighborhood" of specialists who subscribe to the principles of the PCMH. Nephrologists will have an opportunity to practice within this framework, either as the PCMH itself or, more likely, as "neighbors" to the "home." The effective and enthusiastic participation of nephrologists and other specialists will depend on the details of the model, not the least important of which is the financial structure. Dozens of demonstration projects around the country are currently testing the model. If the PCMH model proves to be workable and is widely adopted, nephrologists could be uniquely positioned to participate, given our long experience providing coordinated care for complex patients in a quality-conscious environment. PMID- 22098666 TI - Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma. AB - BACKGROUND/AIMS: Sphingosine kinase 1 (SphK1), which phosphorylates sphingosine to sphingosine-1-phosphate (S1P), is overexpressed in various types of cancers, and may act as an oncogene in tumorigenesis. However, little is known about the precise role of the SphK1/S1P pathway in human liver cancer, especially regarding the metastasis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The expression of SphK1 was detected by quantitative reverse-transcription PCR. In addition, transwell cell migration and invasion assay were carried out for functional analysis. Furthermore, the level of S1P was quantified by ELISA and Rac1/Cdc42 GTPase activation was assessed by western blot analysis. RESULTS: The levels of SphK1 mRNA are commonly up-regulated in HCC patients and human liver cancer cell migration and invasion can be promoted by the overexpression of SphK1. In addition, inhibition of SphK1 with either a SphK1 inhibitor or siRNA reduced human liver cancer cell migration and invasion. Furthermore, overexpression of SphK1 increased S1P levels, and the exogenous addition of S1P increased liver cell migration and invasion through the EDG1 receptor. DISCUSSION AND CONCLUSION: The results from this study provide strong evidence of a role for the SphK1/S1P/EDG1 pathway in liver metastasis, thus making it an attractive therapeutic target for the development of new anti-HCC drugs. PMID- 22098669 TI - Gestational age of previous twin preterm birth as a predictor for subsequent singleton preterm birth. AB - OBJECTIVE: We sought to determine an optimal gestational-age cutoff of preterm twin deliveries for predicting subsequent singleton preterm birth (PTB). STUDY DESIGN: We performed a retrospective study of women with a spontaneous twin delivery who subsequently had a singleton gestation. Univariate and multivariate analyses determined the risk of a spontaneous singleton PTB after a PTB of a twin gestation. Different gestational-age cutoffs of the previous twin PTB were evaluated. RESULTS: Among 255 women, previous twin PTB at <34 weeks' gestation was associated with an increased risk of singleton PTB (odds ratio, 9.67; 95% confidence interval, 3.07-30.47). Every twin gestational age cutoff at <34 weeks' gestation had a significantly higher risk of subsequent singleton PTB, which was no longer significant at >= 34 weeks' gestation (odds ratio, 1.68; 95% confidence interval, 0.23-12.19). CONCLUSION: In women with a previous spontaneous twin PTB at <34 weeks' gestation, there is an increased risk of subsequent singleton PTB. A twin birth at >= 34 weeks' gestation is not associated with an increased risk for a subsequent singleton PTB. PMID- 22098667 TI - Effect of bile duct ligation on bile acid composition in mouse serum and liver. AB - BACKGROUND: Cholestatic liver diseases can be caused by genetic defects, drug toxicities, hepatobiliary malignancies or obstruction of the biliary tract. Cholestasis leads to accumulation of bile acids (BAs) in hepatocytes. Direct toxicity of BAs is currently the most accepted hypothesis for cholestatic liver injury. However, information on which bile acids are actually accumulating during cholestasis is limited. AIM: To assess the BA composition in liver and serum after bile duct ligation (BDL) in male C57Bl/6 mice between 6 h and 14 days and evaluate toxicity of the most abundant BAs. RESULTS: Bile acid concentrations increased in liver (27-fold) and serum (1400-fold) within 6 h after surgery and remained elevated up to 14 days. BAs in livers of BDL mice became more hydrophilic than sham controls, mainly because of increased 6beta-hydroxylation and taurine conjugation. Among the eight unconjugated and 16 conjugated BAs identified in serum and liver, only taurocholic acid (TCA), beta-muricholic acid (betaMCA) and TbetaMCA were substantially elevated representing >95% of these BAs over the entire time course. Although glycochenodeoxycholic acid and other conjugated BAs increased in BDL animals, the changes were several orders of magnitude lower compared with TCA, betaMCA and TbetaMCA. A mixture of these BAs did not cause apoptosis or necrosis, but induced inflammatory gene expression in cultured murine hepatocytes. CONCLUSION: The concentrations of cytotoxic BAs are insufficient to cause hepatocellular injury. In contrast, TCA, betaMCA and TbetaMCA are able to induce pro-inflammatory mediators in hepatocytes. Thus, BAs act as inflammagens and not as cytotoxic mediators after BDL in mice. PMID- 22098670 TI - Effect of hemodialysis and hemofiltration on plasma C.E.R.A. concentrations. AB - C.E.R.A., a continuous erythropoietin receptor activator, is a long-acting erythropoiesis-stimulating agent approved for the treatment of anemia in patients with chronic kidney disease. Although the large molecular weight and the carbohydrate chain make it unlikely that C.E.R.A. could be removed during hemodialysis or hemofiltration, no such data have been published. In vitro studies were performed to assess the removal of C.E.R.A. during hemodialysis and hemofiltration, using both low-flux and high-flux membranes and parameters very similar to those used in clinical practice. Clinical pharmacokinetic studies of plasma C.E.R.A. concentrations in patients undergoing hemodialysis were also performed following subcutaneous injection of C.E.R.A. In the in vitro studies, plasma C.E.R.A. concentrations were not significantly different from baseline values in the primed blood reservoir over a 4-hour period during hemodialysis (P = 0.12). C.E.R.A. concentrations in the plasma obtained from the venous end of the hemofilter increased proportionally with the plasma total protein concentrations, reflecting the consequence of hemoconcentration and suggesting that C.E.R.A and plasma total proteins were retained by hemofiltration membranes to a similar degree. These in vitro studies showed that C.E.R.A. was not removed by simulated hemodialysis or hemofiltration either via transmembrane transport or adsorption to the membrane. The results were corroborated by the clinical pharmacokinetic data, which showed no detectable changes in plasma C.E.R.A. concentrations during hemodialysis using either low-flux or high-flux dialyzers. These results suggest that C.E.R.A. can be administered to patients at any time during hemodialysis or hemofiltration without appreciable loss in the extracorporeal circuit. PMID- 22098671 TI - Oral health of hemodialysis patients: a cross-sectional study at two German dialysis centers. AB - The aim of the study was to investigate the oral hygiene behavior and state of oral health of hemodialysis (HD) patients in Germany. HD patients attending two dialysis centers were asked to participate in the study. Anamneses and oral hygiene behavior were recorded in a questionnaire. Dental examination included the dental status (DMF-T) and the degree of gingival inflammation (PDI: Periodontol Disease Index). Of 129 patients contacted, 54 (42%), aged 63.9 +/- 13.0 years (23 women and 31 men), took part in the study. At an average, dialysis was required for 4.1 years. The cause of terminal renal failure was glomerulonephritis in 30% of patients and diabetic nephropathy in 22% of patients. Since dialysis therapy, 63% of the patients (n = 34) only visited a dentist when they had complaints. In 46 cases (85%), the dentist had been informed about the patient's requirement for dialysis, and in most cases (70%), the dental treatment took place on the day after dialysis. The mean DMF-T of the HD patients was 22.1 +/- 6.5. The proportion of carious teeth was low (D-T: 0.7 +/- 1.2), of missing teeth (M-T) high (16.2 +/- 9.3). The median degree of gingival inflammation (PDI) was 1. Availing themselves of dental treatment after patients needed to have dialysis was mostly "complaint oriented." In addition to a high proportion of missing teeth, a good level of restoration of caries was found. The gingiva showed only a low level of inflammatory changes. PMID- 22098672 TI - A remarkably stable TipE gene cluster: evolution of insect Para sodium channel auxiliary subunits. AB - BACKGROUND: First identified in fruit flies with temperature-sensitive paralysis phenotypes, the Drosophila melanogaster TipE locus encodes four voltage-gated sodium (NaV) channel auxiliary subunits. This cluster of TipE-like genes on chromosome 3L, and a fifth family member on chromosome 3R, are important for the optional expression and functionality of the Para NaV channel but appear quite distinct from auxiliary subunits in vertebrates. Here, we exploited available arthropod genomic resources to trace the origin of TipE-like genes by mapping their evolutionary histories and examining their genomic architectures. RESULTS: We identified a remarkably conserved synteny block of TipE-like orthologues with well-maintained local gene arrangements from 21 insect species. Homologues in the water flea, Daphnia pulex, suggest an ancestral pancrustacean repertoire of four TipE-like genes; a subsequent gene duplication may have generated functional redundancy allowing gene losses in the silk moth and mosquitoes. Intronic nesting of the insect TipE gene cluster probably occurred following the divergence from crustaceans, but in the flour beetle and silk moth genomes the clusters apparently escaped from nesting. Across Pancrustacea, TipE gene family members have experienced intronic nesting, escape from nesting, retrotransposition, translocation, and gene loss events while generally maintaining their local gene neighbourhoods. D. melanogaster TipE-like genes exhibit coordinated spatial and temporal regulation of expression distinct from their host gene but well correlated with their regulatory target, the Para NaV channel, suggesting that functional constraints may preserve the TipE gene cluster. We identified homology between TipE-like NaV channel regulators and vertebrate Slo-beta auxiliary subunits of big-conductance calcium-activated potassium (BKCa) channels, which suggests that ion channel regulatory partners have evolved distinct lineage specific characteristics. CONCLUSIONS: TipE-like genes form a remarkably conserved genomic cluster across all examined insect genomes. This study reveals likely structural and functional constraints on the genomic evolution of insect TipE gene family members maintained in synteny over hundreds of millions of years of evolution. The likely common origin of these NaV channel regulators with BKCa auxiliary subunits highlights the evolutionary plasticity of ion channel regulatory mechanisms. PMID- 22098673 TI - Learning in a simple biological system: a pilot study of classical conditioning of human macrophages in vitro. AB - Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with streptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's < .05), regardless whether they received the conditioned stimulus or not at evocation.However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If further experiments confirm that simple learning can occur in immune cells, this may have bearings not only on immune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly, whether capacities for simple learning in single cells extend beyond habituation, and how this would be demonstrated, remain open questions. PMID- 22098674 TI - Impaired reproductive function of male rats infected with Toxoplasma gondii. AB - Toxoplasmosis is one of the classical conditions known to have an adverse effect on female reproductive functions, but a few investigations into male reproductive parameters have been performed. This work was carried out to study the effects of Toxoplasma gondii on reproductive function in male rats. Male rats were infected with the RH strain of T. gondii tachyzoites, and following every 10 days from 10 to 70 postinfection (PI), the percentage of body weight to testis weight ratio as well as epididymal sperm parameters (number, motility, viability, and morphology rates), serum testosterone (ST), intratesticular testosterone (ITT), serum lactate dehydrogenase (SLDH), intratesticular lactate dehydrogenase and fructose in seminal vesicles and coagulating glands were measured. The results of the study showed sperm motility, viability and concentration rates were significantly decreased temporary after infection up to 70 days. Sperm abnormality was also increased during these days. In addition, temporary alteration in ST, ITT, SLDH, intratesticular LDH and fructose in seminal vesicle and coagulating gland was observed PI. These findings suggest that toxoplasmosis can cause impermanent impairment on the reproductive parameters of male rats. PMID- 22098675 TI - Changes in patterns of persistent halogenated compounds through a pelagic food web in the Baltic Sea. AB - The concentrations and patterns of persistent halogenated compounds (PHCs), including polychlorinated biphenyls (PCBs), DDT, hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB) and polybrominated diphenyl ethers (PBDEs) were examined in a pelagic food web from the southern Baltic Sea consisting of sediment, zooplankton, sprat, Atlantic salmon and anadromous brown trout. Lipid-normalized concentrations generally increased from low trophic levels to high trophic levels, with the exception of HCHs. Due to high concentrations of PBDEs in some zooplankton samples, biomagnification of BDE-47 was only observed for salmon/sprat and trout/sprat. Sprat collected individually and from salmon stomach had significantly different lipid-normalized concentrations and varied in their PHC pattern as well, possibly indicating a large natural variation within the Baltic Sea. The highest lipid-normalized concentrations were found in brown trout. Salmon and brown trout were similar in their PHC pattern suggesting similar food sources. Variation in PHC patterns among trophic levels was not smaller than that among geographically distinct locations, confirming the importance of comparable trophic levels for the assessment of PHC patterns, e.g. for tracing migratory fish. PMID- 22098676 TI - Comparison of multiple estimates of efficacy for influenza vaccine. AB - Influenza vaccine trials typically report vaccine efficacy for infection confirmed symptomatic illness. Data on indirect vaccine efficacy for susceptibility, the degree of vaccine protection to susceptibles, or indirect vaccine efficacy for illness given infection, are sparse. Using inactivated influenza vaccine randomized trial data, we calculated indirect vaccine efficacy for susceptibility of 20% [95% CI 9-30] and indirect vaccine efficacy for illness among infected persons 12% [95% CI 2-22], values inferior to a direct vaccine efficacy for infection-confirmed symptomatic illness of 55% [95% CI -21 to 84] and an indirect effect of 61% [95% CI 8-83]. Such data reveal variance in protective efficacy of the vaccine for multi-dimensional direct and indirect efficacy measures. PMID- 22098677 TI - Adipocyte mitochondrial genes and the forkhead factor FOXC2 are decreased in type 2 diabetes patients and normalized in response to rosiglitazone. AB - BACKGROUND: FOXC2 has lately been implicated in diabetes and obesity as well as mitochondrial function and biogenesis and also as a regulator of mtTFA/Tfam. In this study, the expression of FOXC2 and selected genes involved in mitochondrial function and biogenesis in healthy subjects and in a matched cohort with type 2 diabetes patients before and after treatment with rosiglitazone was determined. Quantitative real time PCR was used to analyze both RNA and DNA from biopsies from subcutaneous adipose tissue. METHODS: Blood samples and subcutaneous abdominal fat biopsies were collected from 12 T2D patients, of which 11 concluded the study, pre-treatment and 90 days after initiation of rosiglitazone treatment, and from 19 healthy control subjects on the first and only visit from healthy subjects. Clinical parameters were measured on the blood samples. RNA and DNA were prepared from the fat biopsies and gene expression was measured with real time PCR. RESULTS: The expression level of genes in the mitochondrial respiratory complexes I - IV were significantly downregulated in the diabetic patients and restored in response to rosiglitazone treatment. Rosiglitazone treatment also increased the relative number of mitochondria in diabetic patients compared with controls. Furthermore, the transcription factors FOXC2 and mtTFA/Tfam displayed a response pattern identical to the mitochondrial genes. CONCLUSIONS: FOXC2, mtTFA/Tfam and subunits of the respiratory complexes I - IV show equivalent regulation in gene expression levels in response to TZD treatment. This, together with the knowledge that FOXC2 has a regulatory function of mtTFA/Tfam and mitochondrial biogenesis, suggests that FOXC2 has a possible functional role in the TZD activated mitochondrial response. PMID- 22098678 TI - Molecular cloning and biochemical characterization of the UDP-glucose: flavonoid 3-O-glucosyltransferase from Concord grape (Vitis labrusca). AB - Glucosylation of anthocyanidin substrates at the 3-O-position is crucial for the red pigmentation of grape berries and wine. The gene that encodes the enzyme involved in this reaction has been cloned from Vitis labrusca cv. Concord, heterologously expressed, and the recombinant enzyme (rVL3GT) was characterized. VL3GT has 96% amino acid sequence identity with Vitis vinifera VV3GT and groups phylogenetically with several other flavonoid 3-O-glycosyltransferases. In vitro substrate specificity studies and kinetic analyses of rVL3GT indicate that this enzyme preferentially glucosylates cyanidin as compared with quercetin. Crude protein extracts from several Concord grape tissues were assayed for glucosyltransferase activity with cyanidin and quercetin as acceptor substrates. A comparison of the VL3GT activities toward with these substrates showed that the 3GT enzyme activity is consistent with the expression of VL3GT in these tissues and is coincident with the biosynthesis of anthocyanins in both location and developmental stages. Enzyme activities in grape mesocarp, pre-veraison exocarp, leaf, flower bud, and flower tissues glucosylated quercetin but not cyanidin at high rates, suggesting the presence of additional enzymes which are able to glucosylate the 3-O-position of flavonols with higher specificity than anthocyanidins. PMID- 22098679 TI - cDNA cloning, genomic structure, molecular characterization and mRNA expression analysis of the Pekin duck interleukin-10 receptor 1. AB - Interleukin-10 (IL-10) mediates its broad anti-inflammatory and immunoregulatory effects through two cell surface receptors by which binding to the IL-10 receptor 1 (IL-10R1) is the initial step that leads to recruitment of IL-10R2 and initiation of the ternary complex signal transduction cascade. The duck IL-10R1 (duIL-10R1) cDNA was obtained by using RT-PCR and 5'RACE. The deduced 574 amino acid protein has an amino acid identity of 62%, 27% and 28% with chicken, mouse and human IL-10R1, respectively. Comparison of the duIL-10R1 cDNA with duck genomic sequences revealed a seven exon-six intron structure of the duck IL-10R1 gene that shares a similar size with the respective exons 1-7 of the chicken and human IL-10R1 genes, but the avian genes are more compact. Promoter analysis identified putative binding sites for regulatory elements such as CCAAT enhancer binding protein-alpha, specificity protein 1 (Sp1), nuclear factor 1 (NF1), transcriptional regulatory protein Oct-1, nuclear factor (NF) kappaB and interferon-stimulated gene factor-3 (ISGF-3). A canonical TATA box was absent in proximity of the transcription initiation site, but a CpG island was present. Sequence analysis of the predicted duIL-10R1 protein revealed characteristic features of class-II cytokine receptors (CFR2) family members and a considerable degree of conservation of residues implicated in ligand binding across higher vertebrates. The predicted secondary structure of the duIL-10R1 extracellular domain is compatible with the two-subdomain structure of the human IL-10R1 protein established by its crystal structure. The 3D model structure shows conservation of the positions of conserved contact residues within four of the five ligand-binding loops. Within the cytoplasmic domain, residues implicated in signal transduction were conserved including two redundant peptide motifs GYXXQ essential for recruitment and activation of STAT3. DuIL-10R1 mRNA expression was most abundant in spleen, thymus, peripheral blood mononuclear cells (PBMCs) and lung. Mitogen stimulation of PBMCs transiently increased duIL-10R1 mRNA expression. Our observations suggest significant evolutionary conservation of the IL-10R1 genomic organization, protein structure and receptor function through the JAK/STAT signalling pathway across higher vertebrates. PMID- 22098680 TI - Comparative effects of processing methods on the feeding value of maize in feedlot cattle. AB - The primary reason for processing maize is to enhance feeding value. Total tract starch digestion is similar for coarsely processed (dry rolled, cracked) dry maize. Enhancements in starch digestion due to dry rolling maize v. feeding maize whole may be greater in light-weight calves than in yearlings, and when DM intake is restricted ( < 1.5 % of body weight). The net energy (NE) maintain (NEm) and NE gain (NEg) values for whole maize are 8.83 and 6.02 MJ (2.11 and 1.44 Mcal)/kg, respectively. Compared with conventional dry processing (i.e. coarse rolled, cracked), finely processing maize may increase the initial rate of digestion, but does not improve total tract starch digestion. Tempering before rolling (without the addition of steam) may enhance the growth performance response and the NE value of maize. Average total tract starch digestion is similar for high-moisture and steam-flaked maize. However, the proportion of starch digested ruminally is greater (about 8 %) for high-moisture maize. The growth performance response of feedlot cattle to the feeding of high-moisture maize is highly variable. Although the NEm and NEg value of whole high-moisture maize was slightly less than that of dry processed maize (averaging 9.04 and 6.44 MJ (2.16 and 1.54 Mcal)/kg, respectively), grinding or rolling high-moisture maize before ensiling increased (6 %) its NE value. Substituting steam-flaked maize for dry processed maize increases average daily gain (6.3 %) and decreases DM intake (5 %). The comparative NEm and NEg values for steam-flaked maize at optimal processing (density = 0.34 kg/l) are 10.04 and 7.07 MJ (2.40 and 1.69 Mcal)/kg, respectively. These NE values are greater (3 %) than current tabular values (National Research Council, 2000), being more consistent with earlier standards (National Research Council, 1984). When maize is the primary or sole source of starch in the diet, concentration of starch in faeces (faecal starch, % of DM) of feedlot steers can serve as an indicator of total tract starch digestion, and, hence, the feeding value of maize. PMID- 22098681 TI - Validation of real-time polymerase chain reaction tests for diagnosing feline immunodeficiency virus infection in domestic cats using Bayesian latent class models. AB - The objectives of the current study were to estimate the sensitivity and specificity of three real-time polymerase chain reaction (PCR) tests for diagnosis of feline immunodeficiency virus (FIV) infection in domestic cats, both individually and when interpreted in series with one of two serological tests, separately in populations of cats at low and high risk of being infected with FIV. One PCR test targeted the pol gene and two targeted the gag gene of FIV. For comparison, sensitivities and specificities of the individual serological tests (IDEXX SNAP((r)) test and AGEN Simplify((r)) test) were also estimated. The study populations consisted of domestic cats thought to be not vaccinated against FIV. Low-risk (males aged 4 years or less and females; n=128) and high-risk (males over 4 years; n=128) cats were selected from those where blood samples were submitted to a commercial clinical pathology service. Bayesian latent class models were used to obtain posterior probability distributions for sensitivity and specificity for each test, based on prior distributions obtained from three experts. Medians of the posterior sensitivity distributions for the PCR tests based on the pol gene and two regions of the gag gene tests ranged from 0.85 to 0.89, compared to 0.89-0.97 for the two serological tests. The medians of posterior specificity distributions for these PCR tests were 0.94-0.96, and 0.95 0.97 for the serological tests. In contrast, the PCR based on one region of the gag gene had lower median sensitivity. Sensitivities of combinations of these serological and PCR tests interpreted in series were low; medians of posterior sensitivity distributions ranged from 0.75 to 0.83. Relative to the low-risk population, median sensitivities in the high-risk population were lower for all tests other than the AGEN Simplify((r)) test; specificities were similar in both populations. We conclude that the sensitivities of the two PCR tests based on the pol gene and two regions of the gag gene, respectively, in non-vaccinated cats are probably lower than the sensitivities of the two serological tests we assessed. We do not recommend screening cats whose FIV vaccination status is uncertain with one of these serological tests and then testing positives with one of these PCR tests because in non-vaccinates, the sensitivities of combinations of these serological and PCR tests interpreted in series are low. Assessment of the validity of these PCR assays in FIV-vaccinated cats is required. PMID- 22098682 TI - Toxoplasma gondii associated behavioural changes in mice, rats and humans: evidence from current research. PMID- 22098683 TI - Impact of computerized physician order entry (CPOE) system on the outcome of critically ill adult patients: a before-after study. AB - BACKGROUND: Computerized physician order entry (CPOE) systems are recommended to improve patient safety and outcomes. However, their effectiveness has been questioned. Our objective was to evaluate the impact of CPOE implementation on the outcome of critically ill patients. METHODS: This was an observational before after study carried out in a 21-bed medical and surgical intensive care unit (ICU) of a tertiary care center. It included all patients admitted to the ICU in the 24 months pre- and 12 months post-CPOE (Misys(r)) implementation. Data were extracted from a prospectively collected ICU database and included: demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, admission diagnosis and comorbid conditions. Outcomes compared in different pre- and post CPOE periods included: ICU and hospital mortality, duration of mechanical ventilation, and ICU and hospital length of stay. These outcomes were also compared in selected high risk subgroups of patients (age 12-17 years, traumatic brain injury, admission diagnosis of sepsis and admission APACHE II > 23). Multivariate analysis was used to adjust for imbalances in baseline characteristics and selected clinically relevant variables. RESULTS: There were 1638 and 898 patients admitted to the ICU in the specified pre- and post-CPOE periods, respectively (age = 52 +/- 22 vs. 52 +/- 21 years, p = 0.74; APACHE II = 24 +/- 9 vs. 24 +/- 10, p = 0.83). During these periods, there were no differences in ICU (adjusted odds ratio (aOR) 0.98, 95% confidence interval [CI] 0.7-1.3) and in hospital mortality (aOR 1.00, 95% CI 0.8-1.3). CPOE implementation was associated with similar duration of mechanical ventilation and of stay in the ICU and hospital. There was no increased mortality or stay in the high risk subgroups after CPOE implementation. CONCLUSIONS: The implementation of CPOE in an adult medical surgical ICU resulted in no improvement in patient outcomes in the immediate phase and up to 12 months after implementation. PMID- 22098684 TI - Evaluation of transient elastography for fibrosis assessment compared with large biopsies in chronic hepatitis B and C. AB - BACKGROUND: Fibrosis determines prognosis and management in patients with chronic hepatitis B and C (CHB and CHC). Transient elastography (TE) is a promising non invasive method to assess fibrosis. We prospectively studied the performance of TE compared to histology and also whether there are differences between CHB and CHC. Only large biopsies (>= 25 mm) were used. METHODS: We included 241 patients with CHB (n = 125) and CHC (n = 116), of whom we acquired 257 liver biopsies, all preceded by elastography. We correlated liver stiffness with fibrosis stage according to the METAVIR system, inflammation (Histology Activity Index), steatosis and iron. The impact of gender, age, body mass index, alcohol, alanine aminotransferase levels, platelet count, viral load and genotype on liver stiffness was evaluated. RESULTS: The AUROC's for F >= 2 were 0.85 for CHB and 0.76 for CHC. AUROC's for F >= 3 were 0.91 for CHB and 0.87 for CHC and 0.90 and 0.91 for F4 for CHB and CHC respectively. For F >= 2 the cut-off value was 6.0 kPa for CHB and 5.0 kPa for CHC. The cut-off values for >= F3 were 9.0 and 8.0 kPa for CHB and CHC, respectively, and 13.0 kPa for F4 in both CHB and CHC patients. Besides inflammation, all other remaining factors do not influence liver stiffness. CONCLUSION: For the diagnosis of fibrosis stages F <= 2 TE is suboptimal, and inflammation may induce higher values. For stages F >= 3 TE performance is good and equal in both CHB and CHC patients. PMID- 22098685 TI - Can a decision-making model be justified in the management of hepatocellular adenoma? AB - During recent years, there was a great development in the area of hepatocellular adenomas (HCA), especially regarding the pathological subtype classification, radiological imaging and management during pregnancy. This review discusses the current knowledge about diagnosis and treatment modalities of HCA and proposes a decision-making model for HCA. A Medline search of studies relevant to epidemiology, histopathology, complications, imaging and management of HCA lesions was undertaken. References from identified articles were hand-searched for further relevant articles. PMID- 22098686 TI - Excess epicardial fat mass misrepresented as cardiomegaly in dry-weight assessment of a dialysis patient. AB - Obesity is a major health problem that has entered the nephrology community and is challenging our conventional management strategies. In this case report, we present a morbidly obese dialysis patient whom dry-weight assessment was disturbed by excess epicardial fat mass due to obesity. This case suggests that problems related to obesity seem not to be limited to dealing with obesity associated kidney injury, chronic kidney disease and mortality, but also other concepts in nephrology such that, as described, excess epicardial fat mass related to morbid obesity in this patient erroneously suggested a high cardiothoracic index, and misled patient management. Interpretation of chest X ray in dry-weight assessment should take into account the patient's body weight especially in obese cases and alternative diagnostic methods for correct determination of fluid status are highly needed. PMID- 22098687 TI - Nocturnality constrains morphological and functional diversity in the eyes of reef fishes. AB - BACKGROUND: Ambient light levels are often considered to drive the evolution of eye form and function. Diel activity pattern is the main mechanism controlling the visual environment of teleost reef fish, with day-active (diurnal) fish active in well-illuminated conditions, whereas night-active (nocturnal) fish cope with dim light. Physiological optics predicts several specific evolutionary responses to dim-light vision that should be reflected in visual performance features of the eye. RESULTS: We analyzed a large comparative dataset on morphological traits of the eyes in 265 species of teleost reef fish in 43 different families. The eye morphology of nocturnal reef teleosts is characterized by a syndrome that indicates better light sensitivity, including large relative eye size, high optical ratio and large, rounded pupils. Improved dim-light image formation comes at the cost of reduced depth of focus and reduction of potential accommodative lens movement. Diurnal teleost reef fish, released from the stringent functional requirements of dim-light vision have much higher morphological and optical diversity than nocturnal species, with large ranges of optical ratio, depth of focus, and lens accommodation. CONCLUSIONS: Physical characteristics of the environment are an important factor in the evolution and diversification of the vertebrate eye. Both teleost reef fish and terrestrial amniotes meet the functional requirements of dim-light vision with a similar evolutionary response of morphological and optical modifications. The trade-off between improved dim-light vision and reduced optical diversity may be a key factor in explaining the lower trophic diversity of nocturnal reef teleosts. PMID- 22098688 TI - Unexpected bilateral massive pulmonary embolism. PMID- 22098690 TI - Endoscopic Saphenous harvesting with an Open CO2 System (ESOS) trial for coronary artery bypass grafting surgery: study protocol for a randomized controlled trial. AB - BACKGROUND: In coronary artery bypass grafting surgery, arterial conduits are preferred because of more favourable long-term patency and outcome. Anyway the greater saphenous vein continues to be the most commonly used bypass conduit. Minimally invasive endoscopic saphenous vein harvesting is increasingly being investigated in order to reduce the morbidity associated with conventional open vein harvesting, includes postoperative leg wound complications, pain and patient satisfaction. However, to date the short and the long-term benefits of the endoscopic technique remain controversial. This study provides an interesting opportunity to address this gap in the literature. METHODS/DESIGN: Endoscopic Saphenous harvesting with an Open CO2 System trial includes two parallel vein harvesting arms in coronary artery bypass grafting surgery. It is an interventional, single centre, prospective, randomized, safety/efficacy, cost/effectiveness study, in adult patients with elective planned and first isolated coronary artery disease. A simple size of 100 patients for each arm will be required to achieve 80% statistical power, with a significant level of 0.05, for detecting most of the formulated hypotheses. A six-weeks leg wound complications rate was assumed to be 20% in the conventional arm and less of 4% in the endoscopic arm. Previously quoted studies suggest a first-year vein-graft failure rate of about 20% with an annual occlusion rate of 1% to 2% in the first six years, with practically no difference between the endoscopic and conventional approaches. Similarly, the results on event-free survival rates for the two arms have barely a 2-3% gap. Assuming a 10% drop-out rate and a 5% cross-over rate, the goal is to enrol 230 patients from a single Italian cardiac surgery centre. DISCUSSION: The goal of this prospective randomized trial is to compare and to test improvement in wound healing, quality of life, safety/efficacy, cost effectiveness, short and long-term outcomes and vein-graft patency after endoscopic open CO2 harvesting system versus conventional vein harvesting.The expected results are of high clinical relevance and will show the safety/efficacy or non-inferiority of one treatment approach in terms of vein harvesting for coronary artery bypass grafting surgery. TRIAL REGISTRATION: www.clinicalTrials.gov NCT01121341. PMID- 22098691 TI - Unusual presentation of a case of Sjogren's syndrome with neurological and ocular manifestation. AB - Sjogren's syndrome is an autoimmune disease that commonly presents to the ophthalmologist as a dry eye disease. We report an unusual presentation of a case of Sjogren's syndrome. A 33-year-old man presented with lid swelling, pseudomembraneous conjunctivitis with central corneal epithelial defect and history of limb weakness for past 2 years. There was progressive enlargement of the epithelial defect and conjunctival-scleral necrosis developed during follow up. Evaluation for underlying connective tissue disorder was positive for SS-B/La antibody and, the rheumatoid factor, anti nuclear antibody, anti neutrophil cytoplasmic antibody titres were negative. Patient was diagnosed as a case of Primary Sjogren's syndrome. Resolution of the conjunctival-scleral necrosis occurred following treatment with combination of cyclosporine and prednisolone. Paramedian tarsorrhaphy was performed to promote healing of the corneal epithelium. The corneal epithelium healed, conjunctival-scleral necrosis resolved completely and the visual acuity improved to 6/36 in the right eye after 3 months of immunosuppressive therapy. The immunosuppressive therapy was discontinued after completion of 6 months of treatment. After 6 months follow-up of stopping immunosuppressive therapy, the ocular and systemic condition is stable. PMID- 22098689 TI - Monthly continuous erythropoietin receptor activator treatment maintains stable hemoglobin levels in routine clinical management of hemodialysis patients. AB - Once-monthly administration of CERA, a continuous erythropoietin receptor activator, has shown equivalent efficacy to shorter-acting erythropoiesis stimulating agents (ESAs) that require more frequent dosing, but data on routine use of once-monthly CERA in hemodialysis patients are lacking. Study on Efficacy, Safety and Applicability of Mircera (SESAM) was a prospective, multicenter, noninterventional trial with a duration of up to 9 months (month 0-5 "titration phase"; month 6-8 "evaluation phase") to test the stability of Hb control in hemodialysis patients under routine conditions. Patient selection, Hb targets and CERA dosing were at the discretion of the local nephrologist. 918 patients from 92 German nephrology centers were included. Ninety-three percent were on ESA treatment prior to study entry. The mean number of CERA dose changes during the study was 1.9 +/- 1.9 per patient. Mean Hb level was 11.4 +/- 1.2 g/dL at baseline and 11.7 +/- 1.4 g/dL at the end of the 8-month study. During the evaluation phase (months 6-8), 15.6%, 40.3%, and 66.0% of patients had stable Hb (i.e., at least two values) in the ranges 11-12, 10-12, and 10-13 g/dL, respectively. The mean intra-individual fluctuation in Hb was 1.4 +/- 0.7 g/dL during the study (0.5 +/- 0.4 g/dL during the 3-month evaluation phase). More than 90% of patients, and > 80% of physicians, rated CERA therapy as "very good" or "good" throughout the study. Four patients (0.4%) discontinued prematurely due to adverse drug reactions. Once-monthly CERA therapy maintains stable Hb values with low intra-individual variability and few dose adaptations in hemodialysis patients when administered entirely according to local practice, and the regimen was well-tolerated. PMID- 22098692 TI - A novel model to explain dietary factors affecting hypocalcaemia in dairy cattle. AB - Most dairy cows exhibit different degrees of hypocalcaemia around calving because the gestational Ca requirements shift to the disproportionately high Ca requirements of lactation. Ca homeostasis is a robust system that effectively adapts to changes in Ca demand or supply. However, these adaptations often are not rapid enough to avoid hypocalcaemia. A delay in the reconfiguration of intestinal Ca absorption and bone resorption is probably the underlying cause of this transient hypocalcaemia. Several dietary factors that affect different aspects of Ca metabolism are known to reduce the incidence of milk fever. The present review describes the interactions between nutrition and Ca homeostasis using observations from cattle and extrapolations from other species and aims to quantitatively model the effects of the nutritional approaches that are used to induce dry cows into an early adaptation of Ca metabolism. The present model suggests that reducing dietary cation-anion difference (DCAD) increases Ca clearance from the blood by dietary induction of systemic acidosis, which results in hypercalciuria due to the loss of function of the renal Ca transient receptor potential vanilloid channel TRPV5. Alternatively, reducing the gastrointestinal availability of Ca by reducing dietary Ca or its nutritional availability will also induce the activation of Ca metabolism to compensate for basal blood Ca clearance. Our model of gastrointestinal Ca availability as well as blood Ca clearance in the transition dairy cow allowed us to conclude that the most common dietary strategies for milk fever prevention may have analogous modes of action that are based on the principle of metabolic adaptation before calving. PMID- 22098693 TI - Patterns of Long Term Care in 29 European countries: evidence from an exploratory study. AB - BACKGROUND: The challenges posed by the rapidly ageing population, and the increased preponderance of disabled people in this group, coupled with the rising level of public expenditure required to service the complex organization of long term care (LTC) delivery are causing increased pressure on LTC systems in Europe. A pan-European survey was carried out to evaluate whether patterns of LTC can be identified across Europe and what are the trends of the countries along them. METHODS: An ecological study was conducted on the 27 EU Member States plus Norway and Iceland, referring to the period 2003-2007. Several variables related to organizational features, elderly needs and expenditure were drawn from OECD Health Data and the Eurostat Statistics database and combined using Multiple Factor Analysis (MFA). RESULTS: Two global Principal Components were taken into consideration given that their expressed total variance was greater than 60%. They were interpreted according to the higher (more than 0.5) positive or negative correlation coefficients between them and the original variables; thus patterns of LTC were identified. High alignment between old age related expenditure and elderly needs characterizes Nordic and Western European countries, the former also having a higher level of formal care than the latter. Mediterranean as well as Central and South Eastern European countries show lower alignment between old age related expenditure and elderly needs, coupled with a level of provision of formal care that is around or slightly above the average European level. In the dynamic comparison, linear, stable or unclear trends were shown for the studied countries. CONCLUSIONS: The analysis carried out is an explorative and descriptive study, which is an attempt to reveal patterns and trends of LTC in Europe, allowing comparisons between countries. It also stimulates further researches with lower aggregated data useful to gain meaningful policy-making evidence.Please see related article: http://www.biomedcentral.com/1741-7015/9/124. PMID- 22098694 TI - Biliary atresia and survival into adulthood without transplantation: a collaborative multicentre clinic review. AB - BACKGROUND: Biliary atresia is a progressive biliary injury which occurs only in infants. AIMS: To review the experience of patients surviving into adulthood without the need for liver transplantation in childhood. METHODS: A multicentre review of patients with biliary atresia treated surgically who survived into adulthood without the need for transplantation. RESULTS: Twenty-two patients were identified across four centres. Median age at the last follow-up was 25 years (range: 18-46), and 21 patients had clinical features of portal hypertension. At last follow-up values of liver enzymes varied from normal to 15 * the upper limit of normal (ULN) for ALT (median 2.11 * ULN) and 9 * the ULN for ALP (median 2.02 * ULN). Six patients had a serum bilirubin > 50 MUmol/l. Pruritus and jaundice were noted in 8 of 20 patients (40%) and 11 of 22 patients (50%) respectively. Thirteen patients (59.1%) were shown to have imaging features of sclerosing cholangitis, with strictures of intrahepatic bile duct(s) (IHBD), dilatation of IHBD (n = 8), or stone(s) within the IHBD (n = 5). A history of presumed bacterial cholangitis was present in 11 patients (50%). Successful pregnancies were recorded in three of fourteen female patients. Four patients underwent transplant between the ages of 20-27 years. Twenty-one patients (95.5%) were alive, including 18 (81.8%) with their native liver at the time of last follow up. CONCLUSIONS: Some patients treated for biliary atresia will survive into adulthood with their native liver, but commonly with secondary biliary disease including cholangitis and portal hypertension. PMID- 22098695 TI - J-tip guide wire entrapment within the heart during central venous catheterization. AB - A 55-year-old female was hospitalized for melena. The patient was suspected of having uremia symptoms. Use of a tunneled cuffed hemodialysis catheter of the right internal jugular vein was planned. At one point, the wire could not be extracted or advanced. In addition, whenever the guide wire was manipulated, ventricular premature rhythms developed. Fluoroscopy revealed knotting of the guide wire in the right ventricle. A 7 French guiding catheter was inserted along the guide wire, which loosened the knotting of the guide wire. The present case shows that entrapment within the heart can develop due to use of a J-tip guide wire. If a guide wire cannot be removed despite several attempts with gentle pressure, this event should be ruled out by fluoroscopy and chest X-ray. Using of straight or curved guide wire and real-time surveillance using fluoroscopy or electrocardiography may be important to prevent this complication. PMID- 22098696 TI - Genetic continuity across a deeply divergent linguistic contact zone in North Maluku, Indonesia. AB - BACKGROUND: The islands of North Maluku, Indonesia occupy a central position in the major prehistoric dispersal streams that shaped the peoples of Island Southeast Asia and the Pacific. Within this region a linguistic contact zone exists where speakers of Papuan and Austronesian languages reside in close proximity. Here we use population genetic data to assess the extent to which North Maluku populations experienced admixture of Asian genetic material, and whether linguistic boundaries reflect genetic differentiation today. RESULTS: Autosomal and X-linked markers reveal overall Asian admixture of 67% in North Maluku, demonstrating a substantial contribution of genetic material into the region from Asia. We observe no evidence of population structure associated with ethnicity or language affiliation. CONCLUSIONS: Our data support a model of widespread Asian admixture in North Maluku, likely mediated by the expansion of Austronesian-speaking peoples into the region during the mid Holocene. In North Maluku there is no genetic differentiation in terms of Austronesian- versus Papuan-speakers, suggesting extensive gene flow across linguistic boundaries. In a regional context, our results illuminate a major genetic divide at the Molucca Sea, between the islands of Sulawesi and North Maluku. West of this divide, populations exhibit predominantly Asian ancestry, with very little contribution of Papuan genetic material. East of the Molucca Sea, populations show diminished rates of Asian admixture and substantial persistence of Papuan genetic diversity. PMID- 22098697 TI - Homogeneous single-label biochemical Ras activation assay using time-resolved luminescence. AB - Mutations of the small GTP-binding protein Ras have been commonly found in tumors, and Ras oncogenes have been established to be involved in the early steps of cancerogenesis. The detection of Ras activity is critical in the determination of the cell signaling events controlling cell growth and differentiation. Therefore, development of improved methods for primary screening of novel potential drugs that target small GTPase or their regulators and their signaling pathways is important. Several assays have been developed for small GTPases studies, but all these methods have limitations for a high-throughput screening (HTS) use. Multiple steps including separation, use of radioactive labels or time consuming immunoblotting, and a need of large quantities of purified proteins are decreasing the user-friendliness of these methods. Here, we have developed a homogeneous H-Ras activity assay based on a single-label utilizing the homogeneous quenching resonance energy transfer technique (QRET). In the QRET method, the binding of a terbium-labeled GTP (Tb-GTP) to small GTPase protein H Ras protects the signal of the label from quenching, whereas the signal of the nonbound fraction of Tb-GTP is quenched by a soluble quencher. This enables a rapid determination of the changes in the activity status of Ras. The assay optimization showed that only 60 nM concentration of purified H-Ras protein was needed. The functionality of the assay was proved by detecting the effect of H Ras guanine nucleotide exchange factor, Son of Sevenless. The signal-to background ratio up to 7.7 was achieved with an average assay coefficient of variation of 9.1%. The use of a low concentration of purified protein is desirable and the signal-to-background ratio of 3.4 was achieved in the assay at a concentration of 60 nM for H-Ras and SOS proteins. The need of only one labeled molecule and the ability to decrease the quantities of purified proteins used in the experiments are valuable qualities in HTS showing the potential of the QRET method. PMID- 22098698 TI - Use of an alteplase algorithm for the management of hemodialysis catheter dysfunction. AB - Hemodialysis (HD) catheter dysfunction compromises HD adequacy and increases the cost of patient care. Repeated administration of alteplase in HD catheters typically produces only short-term benefits. The purpose of this study was to design, implement, and evaluate the efficacy of an experimental alteplase algorithm to manage HD catheter dysfunction. This was a two-part prospective nonrandomized study. Baseline data of alteplase use and catheter exchange were collected during part 1 of the study. Part 2 consisted of the alteplase algorithm implementation and repeat collection of catheter data. Rates of alteplase use and catheter exchange per 1000 catheter-days were the primary and secondary outcomes of the study. One hundred and seventy-two catheters in 131 patients were followed prospectively during the course of the study. The adjusted relative rate (RR) of alteplase use showed no significant difference between both parts of the study, adjusted RR: 1.10, 95% confidence interval (CI) (0.73-1.65). Similarly, catheter exchange rates were not significantly different over the duration of the study (1.12 vs. 1.03 per 1000 catheter-days). However, waiting time for catheter exchange increased from 20.36 +/- 14 days in part 1 to 38.42 +/- 28 days in part 2 (P < 0.05). The alteplase algorithm did not significantly reduce alteplase use. This may be partially explained by repeated use of alteplase in part 2, due to longer waiting times for catheter exchange procedures. PMID- 22098699 TI - Primary care physicians' perspectives towards managing rheumatoid arthritis: room for improvement. AB - INTRODUCTION: Many people with rheumatoid arthritis (RA) do not receive care from a rheumatologist. We surveyed primary care physicians (PCPs) to better understand their attitudes, knowledge, and practices regarding the optimal treatment of RA. METHODS: Randomly selected PCPs practicing in the US were surveyed. The survey encompassed their experience with RA, use of disease modifying anti-rheumatic drugs (DMARDs), and experience with rheumatology referrals. Logistic regression analyses described the responses and examined the correlation between physician variables and use of DMARDs. RESULTS: E-mail invitations were opened by 1, 103 PCPs and completed by 267 (25%). Most respondents were men (68%) in practice for over 10 years (64%) who reported 6 or more RA patients under their care in the last year (71%). The majority reported some RA training after medical school (59%), but only one-third felt very confident managing this condition. Most (81%) reported prescribing DMARDs, but 37% do not initiate them, with only 9% reporting being very confident starting a DMARD. In unadjusted analyses, several respondent characteristics were strongly associated with not prescribing DMARDs, but none was significant after adjustment. Almost half (44%) of PCPs noted that patients report difficulty getting appointments with rheumatologists. CONCLUSIONS: We found many PCPs are uncomfortable managing RA with DMARDs, despite common beliefs that their patients lack access to a rheumatologist. Lack of accessibility to rheumatologists and discomfort in prescribing DMARDs for patients with RA are potential barriers to optimal treatment. PMID- 22098700 TI - A trial for the use of qigong in the treatment of pre and mild essential hypertension: a study protocol for a randomized controlled trial. AB - BACKGROUND: Hypertension is a risk factor for cardiovascular disease, and the prevalence of hypertension tends to increase with age. Current treatments for hypertension have side effects and poor adherence. Qigong has been studied as an alternative therapy for hypertension; however, the types of qigong used in those studies were diverse, and there have not been many well-designed randomized controlled trials.Our objectives are the following: 1) To evaluate the effects of qigong on blood pressure, health status and hormone levels for pre- or mild hypertension. 2) To test the methodological appropriateness of this clinical trial and calculate a sample size for future randomized trials. METHODS: Forty subjects with pre- or mild hypertension will be randomized to either the qigong exercise group or the non-treated group. Participants in the qigong group will conduct qigong exercises 5 times per week for 8 weeks, and participants in the non-treated group will maintain their current lifestyle, including diet and exercise. The use of antihypertensive medication is not permitted. The primary endpoint is a change in patient blood pressure. Secondary endpoints are patient health status (as measured by the SF-36 and the MYMOP2 questionnaires) and changes in hormone levels, including norepinephrine, epinephrine, and cortisol. DISCUSSION: This study will be the first randomized trial to investigate the effectiveness of qigong exercises for the treatment of pre- and mild hypertension. The results of this study will help to establish the optimal approach for the care of adults with pre- or mild hypertension. TRIAL REGISTRATION: Clinical Research Information Service KCT0000140. PMID- 22098701 TI - Antibacterial activities of 4-substituted-2-[(E)-{(1S,2R)/(1R,2S)-1-hydroxy-1 phenylpropan-2-ylimino}methyl]phenol. AB - A series of norephedrine-based Schiff bases (1a-6a and 1b-6b) were synthesized by reacting substituted salicylaldehydes with d-norephedrine or l-norephedrine. The structure of these compounds was confirmed by elemental analyses and spectroscopic techniques. The molecular structures of 5a and 6a have been determined by X-ray crystallography, which revealed that the compounds are in the oxoamino form, with bent intramolecular N-H...O (N...O ~ 2.58 A) hydrogen bonds and that they are associated in dimers bridged by linear intermolecular O-H...O (O...O ~ 2.69 A) hydrogen bonds. The density functional theory calculations on 5a confirmed that the oxoamino form is more stable than the phenolimino form by 12.2 kcal/mol. All the compounds were evaluated for their antibacterial activity using resazurin dye as indicator by twofold dilution method against four bacteria namely, Bacillus subtilis (NCIM2718), Staphylococcus aureus (NCIM5021), Escherichia coli (NCIM2931), and Proteus vulgaris (NCIM2813). PMID- 22098702 TI - Role transition from mental health nurse to IAPT high intensity psychological therapist. AB - BACKGROUND: The Improving Access to Psychological Therapies (IAPT) initiative has depended on the training of a new NHS mental health workforce. At step 3 of the stepped care model, capacity building has required the recruitment of a wide range of mental health professionals into high intensity therapists training posts. This shift naturally entails role transition on the part of trainees into delivering cognitive behavioural psychotherapy (CBP), but no previous research has examined the experience of such transitions. AIM: To describe the lived experience of transition from mental health nurse to IAPT high intensity therapist and to identify possible factors which moderate effective role conversions. METHOD: Six qualified high intensity therapists were interviewed using a semi-structured interview and the subsequent interviews transcribed. Thematic content analysis (TCA) was used to analyze personal accounts of role transition. All participants had previously been mental health nurses and attended the same IAPT high intensity therapist (HIT) training programme. RESULTS: Six key themes were apparent from the TCA. Three interconnected themes concerning supervision (style, impact of approach and historical context) and three additional themes of the challenge of learning a new clinical approach, high need for support, and forming a new psychotherapist identity. CONCLUSIONS: Findings suggest supervision is the most important factor in supporting complex psychotherapy role transitions. Clinical supervisors may need to incorporate dedicated time on role and identity shift during CBP training to ensure effective assimilation and transition. Methodological short-comings are identified and discussed. PMID- 22098704 TI - Can 24-h urine sodium excretion be replaced by spot urine sodium/potassium in patients with decompensated cirrhosis? PMID- 22098703 TI - Reconstruction versus conservative treatment after rupture of the anterior cruciate ligament: cost effectiveness analysis. AB - BACKGROUND: The decision whether to treat conservatively or reconstruct surgically a torn anterior cruciate ligament (ACL) is an ongoing subject of debate. The high prevalence and associated public health burden of torn ACL has led to continuous efforts to determine the best therapeutic approach. A critical evaluation of benefits and expenditures of both treatment options as in a cost effectiveness analysis seems well-suited to provide valuable information for treating physicians and healthcare policymakers. METHODS: A literature review identified four of 7410 searched articles providing sufficient outcome probabilities for the two treatment options for modeling. A transformation key based on the expert opinions of 25 orthopedic surgeons was used to derive utilities from available evidence. The cost data for both treatment strategies were based on average figures compiled by Orthopaedic University Hospital Balgrist and reinforced by Swiss national statistics. A decision tree was constructed to derive the cost-effectiveness of each strategy, which was then tested for robustness using Monte Carlo simulation. RESULTS: Decision tree analysis revealed a cost effectiveness of 16,038 USD/0.78 QALY for ACL reconstruction and 15,466 USD/0.66 QALY for conservative treatment, implying an incremental cost effectiveness of 4,890 USD/QALY for ACL reconstruction. Sensitivity analysis of utilities did not change the trend. CONCLUSION: ACL reconstruction for reestablishment of knee stability seems cost effective in the Swiss setting based on currently available evidence. This, however, should be reinforced with randomized controlled trials comparing the two treatment strategies. PMID- 22098705 TI - Personal viewpoint: hemodialysis--water, power, and waste disposal: rethinking our environmental responsibilities. AB - While medical health professionals are trained to detect, treat, and comfort, they are not trained to consider the environmental impact of the services they provide. Dialysis practitioners seem particularly careless in the use of natural resources-especially water and power-and seem broadly ignorant of the profound medical waste issues created by single use dialysis equipment. If the data we have collected is an indication, then extrapolation of this data to a dialysis population currently estimated at ~2 million patients worldwide, a "world dialysis service" would use ~156 billion liters of water and discard ~2/3 of that during reverse osmosis. This waste occurs, despite the discarded water being high grade "gray water" of potable standard. The same world dialysis service would consume 1.62 billion kWh of power-mostly generated from coal and other environmentally damaging sources. Our world dialysis service, based on ~2 kg of waste from each dialysis treatment, would generate ~625,000 tonnes of plastic waste-waste that would be potentially reusable if simple sterilizing techniques were applied to it at the point of generation. Dialysis services must begin to explore eco-dialysis potentials. The continued plundering of resources without considering reuse or recycling, exploration of renewable energy options, or the reduction of the carbon footprint of the dialysis process . . . is unsustainable. Sustainable dialysis practices should be a global goal in the coming decade. PMID- 22098706 TI - DNA methylation changes elicited by social stimuli in the brains of worker honey bees. AB - Social environments are notoriously multifactorial, yet studies in rodents have suggested that single variables such as maternal care can in fact be disentangled and correlated with specific DNA methylation changes. This study assesses whether non-detrimental social environmental variation in a highly plastic social insect is correlated with epigenomic modifications at the DNA methylation level. Honey bee workers perform tasks such as nursing and foraging in response to the social environment in the hive, in an age-linked but not age-dependent manner. In this study, the methylation levels of 83 cytosine-phosphate-guanosine dinucleotides over eight genomic regions were compared between the brains of age-matched bees performing nursing or foraging tasks. The results reveal more changes correlated with task than with chronological age, and also hive-associated methylation at some sites. One methylation site from a gene encoding Protein Kinase C binding protein 1 was consistently more methylated in foragers than nurses, which is suggested to lead to production of task-specific protein isoforms via alternative splicing. This study illustrates the ability of the neural epigenome to dynamically respond to complex social stimuli. PMID- 22098707 TI - Renal involvement of mantle cell lymphona leading to end stage renal disease. AB - Mantle cell lymphoma (MCL), owing to its insensitivity to chemotherapy, has a poor prognosis, with a median survival of 3 years to 4 years. MCL frequently infiltrates other organs. However, reports involving kidney in living patients are rare. Here, we report a case of MCL with renal involvement leading to end stage renal disease that required renal replacement therapy. A 69-year-old man diagnosed with MCL 3 years earlier was admitted to our emergency room due to uremic symptoms. After eight cycles of chemotherapy, he had displayed complete remission, but experienced a recurrence 1.5 years later; after refusing chemotherapy, the patient was lost on follow-up in the final 10 months. On presentation at the emergency room, the patient's serum blood urea nitrogen was 109.5 mg/dL, and creatinine was 11.1 mg/dL. All serological markers for secondary glomerulonephritis were negative. Renal biopsy revealed 50% sclerosis of the glomerulus and small dense lymphocyte infiltration of the tubulo-interstitium. Similar cells were found on the gastric mucosa. Despite our recommendation for chemotherapy, he refused all treatments except for hemodialysis, which was maintained for 12 months until his death. This patient represents the first case report of the renal involvement of MCL leading to end stage renal disease. PMID- 22098708 TI - Bed rest or mobilization after rt-PA? A case-crossover study of factors influencing clinical decision making in stroke services. AB - BACKGROUND: Acute stroke management is a dynamic field. Treatment with recombinant tissue plasminogen activator is standard care in Australia, but there are no evidence-based practice guidelines about first out of bed activity (mobilization) after recombinant tissue plasminogen activator. AIMS: To identify factors influencing clinicians' decisions to delay or allow mobilization. METHODS: Case-crossover design. Using hypothetical case vignettes, we explored the factors that clinicians consider when deciding to first mobilize a patient after recombinant tissue plasminogen activator. Acute stroke physicians and nurses from Australian hospitals known to treat with recombinant tissue plasminogen activator participated. Information about hospital recombinant tissue plasminogen activator protocols and perceived benefits and harms of mobilization after recombinant tissue plasminogen activator were also captured. RESULTS: Fifty four clinicians, 52% senior nurses, and 48% senior physicians from all states of Australia participated. Of the factors influencing decisions about mobilization after recombinant tissue plasminogen activator, neurological decline (0.29; confidence interval 0.12, 0.46; P = 0.001), neurological decline with symptomatic intracerebral hemorrhage (0.41; confidence interval 0.24, 0.59; P < 0.0001), infection of uncertain cause (0.32; confidence interval 0.14, 0.50; P = 0.001), severe chest infection (0.35; confidence interval 0.16, 0.53; P = 0.0004), severe stroke (0.29; confidence interval 0.12, 0.46; P = 0.001), drowsiness (0.47; confidence interval 0.29, 0.63; P < 0.0001), and confusion (0.31; confidence interval 0.15, 0.47; P = 0.0001) significantly influenced decisions. Falls risk was a common concern (85%). CONCLUSION: Growing interest in development of clear protocols that guide first mobilization after recombinant tissue plasminogen activator prompted this study. We have identified factors that may influence decisions about when to allow patients to mobilize after recombinant tissue plasminogen activator. These, combined with emerging evidence of risks and benefits of early mobilization, should help protocol development in the future. PMID- 22098710 TI - Increase in periosteal angiogenesis through heat shock conditioning. AB - OBJECTIVE: It is widely known that stress conditioning can protect microcirculation and induce the release of vasoactive factors for a period of several hours. Little, however, is known about the long-term effects of stress conditioning on microcirculation, especially on the microcirculation of the periosteum of the calvaria. For this reason, we used intravital fluorescence microscopy to investigate the effects of heat shock priming on the microcirculation of the periosteum over a period of several days. METHODS: Fifty two Lewis rats were randomized into eight groups. Six groups underwent heat shock priming of the periosteum of the calvaria at 42.5 degrees C, two of them (n = 8) for 15 minutes, two (n = 8) for 25 minutes and two (n = 8) for 35 minutes. After 24 hours, a periosteal chamber was implanted into the heads of the animals of one of each of the two groups mentioned above. Microcirculation and inflammatory responses were studied repeatedly over a period of 14 days using intravital fluorescence microscopy. The expression of heat shock protein (HSP) 70 was examined by immunohistochemistry in three further groups 24 hours after a 15 minute (n = 5), a 25-minute (n = 5) or a 35-minute (n = 5) heat shock treatment. Two groups that did not undergo priming were used as controls. One control group (n = 8) was investigated by intravital microscopy and the other (n = 5) by immunohistochemistry. RESULTS: During the entire observation period of 14 days, the periosteal chambers revealed physiological microcirculation of the periosteum of the calvaria without perfusion failures. A significant (p < 0.05) and continuous increase in functional capillary density was noted from day 5 to day 14 after 25-minute heat shock priming. Whereas a 15-minute exposure did not lead to an increase in functional capillary density, 35-minute priming caused a significant but reversible perfusion failure in capillaries. Non-perfused capillaries in the 35-minute treatment group were reperfused by day 10. Immunohistochemistry demonstrated an increase in cytoprotective HSP70 expression in the periosteum after a 15-minute and a 35-minute heat shock pretreatment when compared with the control group. The level of HSP70 expression that was measured in the periosteum after 25 minutes of treatment was significantly higher than the levels observed after 15 or 35 minutes of heat shock exposure. CONCLUSION: A few days after heat shock priming over an appropriate period of time, a continuous increase in functional capillary density is seen in the periosteum of the calvaria. This increase in perfusion appears to be the result of the induction of angiogenesis. PMID- 22098711 TI - AGA standards for gastroenterologists for performing and interpreting diagnostic computed tomography colonography: 2011 update. PMID- 22098709 TI - Microplate-based platform for combined chromatin and DNA methylation immunoprecipitation assays. AB - BACKGROUND: The processes that compose expression of a given gene are far more complex than previously thought presenting unprecedented conceptual and mechanistic challenges that require development of new tools. Chromatin structure, which is regulated by DNA methylation and histone modification, is at the center of gene regulation. Immunoprecipitations of chromatin (ChIP) and methylated DNA (MeDIP) represent a major achievement in this area that allow researchers to probe chromatin modifications as well as specific protein-DNA interactions in vivo and to estimate the density of proteins at specific sites genome-wide. Although a critical component of chromatin structure, DNA methylation has often been studied independently of other chromatin events and transcription. RESULTS: To allow simultaneous measurements of DNA methylation with other genomic processes, we developed and validated a simple and easy-to-use high throughput microplate-based platform for analysis of DNA methylation. Compared to the traditional beads-based MeDIP the microplate MeDIP was more sensitive and had lower non-specific binding. We integrated the MeDIP method with a microplate ChIP assay which allows measurements of both DNA methylation and histone marks at the same time, Matrix ChIP-MeDIP platform. We illustrated several applications of this platform to relate DNA methylation, with chromatin and transcription events at selected genes in cultured cells, human cancer and in a model of diabetic kidney disease. CONCLUSION: The high throughput capacity of Matrix ChIP-MeDIP to profile tens and potentially hundreds of different genomic events at the same time as DNA methylation represents a powerful platform to explore complex genomic mechanism at selected genes in cultured cells and in whole tissues. In this regard, Matrix ChIP-MeDIP should be useful to complement genome-wide studies where the rich chromatin and transcription database resources provide fruitful foundation to pursue mechanistic, functional and diagnostic information at genes of interest in health and disease. PMID- 22098712 TI - Insulin resistance increases the occurrence of new cardiovascular events in patients with manifest arterial disease without known diabetes. the SMART study. AB - BACKGROUND: Insulin resistance is accompanied by a cluster of metabolic changes, often referred to as metabolic syndrome. Metabolic syndrome is associated with an increased cardiovascular risk in patients with manifest arterial disease. We investigated whether insulin resistance is associated with an increased risk for cardiovascular events in patients with manifest arterial disease without known diabetes and whether this can be explained by the components of the metabolic syndrome or by inflammation. METHODS: Prospective cohort study in 2611 patients with manifest arterial disease without known diabetes. Homeostasis model of insulin resistance (HOMA-IR) was used to quantify insulin resistance. The relation of HOMA-IR with cardiovascular events (vascular death, myocardial infarction or stroke) and all cause mortality was assessed with Cox regression analysis. In additional models adjustments were performed for the single components constituting the metabolic syndrome and for inflammation. RESULTS: HOMA-IR increases with the number of metabolic syndrome components (mean HOMA-IR +/- SD in groups with 0, 1, 2, 3, 4 and 5 metabolic syndrome components: 1.4 +/- 0.7; 1.8 +/- 1.2; 2.4 +/- 1.5; 3.1 +/- 1.8; 4.0 +/- 2.6; and 5.6 +/- 3.6 respectively). High HOMA-IR was independently associated with an increased risk of cardiovascular events (tertile 2 vs. 1 HR 1.92; 95%CI 1.20-3.08) (tertile 3 vs.1 HR 1.78; 95%CI 1.10-2.89) and with all cause mortality (tertile 2 vs. 1 HR 1.80; 95%CI 1.04-3.10) (tertile 3 vs.1 HR 1.56; 95%CI 0.88-2.75). These relations were not influenced by the individual components of metabolic syndrome or by inflammation. CONCLUSIONS: In patients with manifest arterial disease without known diabetes, insulin resistance increases with the number of metabolic syndrome components, and elevated insulin resistance increases the risk of new cardiovascular events. PMID- 22098714 TI - Hospital-based injury data from level III institution in Cameroon: retrospective analysis of the present registration system. AB - BACKGROUND: Data on the epidemiology of trauma in Cameroon are scarce. Presently, hospital records are still used as a primary source of injury data. It has been shown that trauma registries could play a key role in providing basic data on trauma. Our goal is to review the present emergency ward records for completeness of data and provide an overview of injuries in the city of Limbe and the surrounding area in the Southwest Region of Cameroon prior to the institution of a formal registration system. METHODS: A retrospective review of Emergency Ward logs in Limbe Hospital was conducted over one year. Records for all patients over 15 years of age were reviewed for 14 data points considered to be essential to a basic trauma registry. Completeness of records was assessed and a descriptive analysis of patterns and trends of trauma was performed. RESULTS: Injury-related conditions represent 27% of all registered admissions in the casualty department. Information on age, sex and mechanism of injury was lacking in 22% of cases. Information on vital signs was present in 2% (respiratory rate) to 12% (blood pressure on admission) of records. Patient disposition (admission, transfer, discharge, or death) was available 42% of the time, whilst location of injury was found in 84% of records. Road traffic injury was the most frequently recorded mechanism (36%), with the type of vehicle specified in 54% and the type of collision in only 22% of cases. Intentional injuries were the second most frequent mechanism at 23%. CONCLUSION: The frequency of trauma found in this context argues for further prevention and treatment efforts. The institution of a formal registration system will improve the completeness of data and lead to increased ability to evaluate the severity and subsequent public health implications of injury in this region. PMID- 22098715 TI - Development and piloting of the Fiji Injury Surveillance in Hospitals System (TRIP Project-1). AB - INTRODUCTION: Whilst more than 90% of injury related deaths are estimated to occur in low-and-middle-income countries (LMICs), the epidemiology of fatal and hospitalised injuries in Pacific Island Countries has received scant attention. This study describes the development and piloting of a population-based trauma registry in Fiji to address this gap in knowledge. METHODS: The Fiji Injury Surveillance in Hospitals (FISH) system was an active surveillance system designed to identify injuries resulting in death or a hospital admission in Viti Levu, Fiji. During the pilot conducted over five months in 2005, Accident and Emergency registers, admission folders and morgue registers from 8 of Viti Levu's 12 hospitals, and an additional 3 hospitals in other parts of the country were reviewed by hospital staff and medical students to identify cases and extract a minimum data set that included demographic factors; the mechanism, nature and context of injury; substance use; and discharge outcomes. The system was audited to identify and redress difficulties with data quality in a manner that also supported local capacity development and training in injury surveillance and data management. RESULTS: This pilot study demonstrated the potential to collect high quality data on injuries that can pose a significant threat to life in Fiji using a mechanism that also increased the capability of health professionals to recognise the significance of injury as a public health issue. CONCLUSION: The injury surveillance system piloted provides the opportunity to inform national injury control strategies in Fiji and increase the capacity for injury prevention and more focused research addressing risk factors in the local context. PMID- 22098716 TI - Development of a quantification method for digoxin, a typical P-glycoprotein probe in clinical and non-clinical studies, using high performance liquid chromatography-tandem mass spectrometry: the usefulness of negative ionization mode to avoid competitive adduct-ion formation. AB - Highly sensitive and accurate liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods have been developed and validated for measuring digoxin (DGX), a typical P-glycoprotein probe, in human plasma, rat plasma, and rat brain. We extracted DGX and deuterium-labeled DGX (as internal standard) from sample fluids under basic conditions using acetonitrile and sodium chloride-saturated 0.1 mol/L sodium hydroxide. The upper organic layer was diluted with distilled water, and the resulting solution was injected into an LC/MS/MS system in negative ionization mode. Chromatographic separation was achieved on a C(18)-ODS column in the gradient mobile phase, which comprised 0.05% (w/v) ammonium carbonate (pH 9.0) and methanol at a flow rate of 0.7 mL/min. Regardless of the type of biological matrix, intra-day and inter-day validation tests demonstrated good linearity of calibration curves within ranges of 0.1-10 ng/mL for plasma and 0.5 50 ng/g for rat brain and gave excellent accuracy and precision of quality control samples at 4 concentration levels. Unlike existing methods, our approach uses negative ionization to avoid competitive adduct formation of DGX. Our method showed higher sensitivity and wider applicability to various types of biological matrices than existing methods. Our method will support clinical and preclinical investigation of in vivo P-glycoprotein functionality using DGX. PMID- 22098717 TI - Capillary electrophoretic determination of DNA damage markers: content of 8 hydroxy-2'-deoxyguanosine and 8-nitroguanine in urine. AB - A sensitive and low-cost analytical method has been developed to determine 8 hydroxy-2'-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO(2)Gua) based on capillary electrophoresis with amperometric detection (CE-AD) after solid phase extraction (SPE). Under optimized condition, these two markers were well separated from other components coexisting in urine, exhibiting a linear calibration over the concentration range of 0.1-50.0 MUg/mL with the detection limits ranging from 0.02 to 0.06 MUg/mL. The relative standard deviations (RSDs) were in the range of 0.1-2.1% for peak area, 0.1-1.5% for migration time, respectively. The average recovery and RSD were within the range of 100.0-108.0% and 0.1-1.7%, respectively. It was found that the urinary contents of 8-OHdG and 8-NO(2)Gua in cancer patients were significantly higher than those in healthy ones. PMID- 22098718 TI - The siderophore-interacting protein YqjH acts as a ferric reductase in different iron assimilation pathways of Escherichia coli. AB - Siderophore-interacting proteins (SIPs), such as YqjH from Escherichia coli, are widespread among bacteria and commonly associated with iron-dependent induction and siderophore utilization. In this study, we show by detailed biochemical and genetic analyses the reaction mechanism by which the YqjH protein is able to catalyze the release of iron from a variety of iron chelators, including ferric triscatecholates and ferric dicitrate, displaying the highest efficiency for the hydrolyzed ferric enterobactin complex ferric (2,3-dihydroxybenzoylserine)(3). Site-directed mutagenesis revealed that residues K55 and R130 of YqjH are crucial for both substrate binding and reductase activity. The NADPH-dependent iron reduction was found to proceed via single-electron transfer in a double displacement-type reaction through formation of a transient flavosemiquinone. The capacity to reduce substrates with extremely negative redox potentials, though at low catalytic rates, was studied by displacing the native FAD cofactor with 5 deaza-5-carba-FAD, which is restricted to a two-electron transfer. In the presence of the reconstituted noncatalytic protein, the ferric enterobactin midpoint potential increased remarkably and partially overlapped with the effective E(1) redox range. Concurrently, the observed molar ratios of generated Fe(II) versus NADPH were found to be ~1.5-fold higher for hydrolyzed ferric triscatecholates and ferric dicitrate than for ferric enterobactin. Further, combination of a chromosomal yqjH deletion with entC single- and entC fes double deletion backgrounds showed the impact of yqjH on growth during supplementation with ferric siderophore substrates. Thus, YqjH enhances siderophore utilization in different iron acquisition pathways, including assimilation of low-potential ferric substrates that are not reduced by common cellular cofactors. PMID- 22098720 TI - Super-resolution fluorescence microscopy as a tool to study the nanoscale organization of chromosomes. AB - Chromatin organization spans a wide range of structural complexity. Substructures at the 10-200nm scale are poorly characterized, especially in living cells, due to the limitations of electron microscopy and standard optical microscopy. Recently developed super-resolution fluorescence microscopy methods represent an exciting opportunity to access those substructures, and recent progress with these techniques has yielded insights into chromatin organization at different condensation stages. Recent studies have focused on confronting the challenges that are specific to chromatin super-resolution imaging, such as the high packing density of mitotic chromosomes and difficulties in interpreting interphase chromatin images. Building on these first results and with ongoing rapid technical advances in super-resolution fluorescence imaging there is great potential to uncover new features with unprecedented detail. PMID- 22098719 TI - Functional imaging of proteases: recent advances in the design and application of substrate-based and activity-based probes. AB - Proteases are enzymes that cleave peptide bonds in protein substrates. This process can be important for regulated turnover of a target protein but it can also produce protein fragments that then perform other functions. Because the last few decades of protease research have confirmed that proteolysis is an essential regulatory process in both normal physiology and in multiple disease associated conditions, there has been an increasing interest in developing methods to image protease activity. Proteases are also considered to be one of the few 'druggable' classes of proteins and therefore a large number of small molecule based inhibitors of proteases have been reported. These compounds serve as a starting point for the design of probes that can be used to target active proteases for imaging applications. Currently, several classes of fluorescent probes have been developed to visualize protease activity in live cells and even whole organisms. The two primary classes of protease probes make use of either peptide/protein substrates or covalent inhibitors that produce a fluorescent signal when bound to an active protease target. This review outlines some of the most recent advances in the design of imaging probes for proteases. In particular, it highlights the strengths and weaknesses of both substrate-based and activity-based probes and their applications for imaging cysteine proteases that are important biomarkers for multiple human diseases. PMID- 22098721 TI - NOD2 gene variants and spontaneous bacterial peritonitis. PMID- 22098722 TI - Might cholesterol sulfate deficiency contribute to the development of autistic spectrum disorder? AB - Autism is a condition characterized by impaired cognitive and social skills, often associated with compromised immune function. There has been considerable concern recently that the incidence of autism is alarmingly on the rise, especially in Western nations, and environmental factors are increasingly suspected to play a role. In this paper, we propose a novel hypothesis for a principle cause of autism, namely insufficient supply of cholesterol sulfate to the fetus during gestation and the infant postnatally. We hypothesize that main contributory factors are insufficient sun exposure and insufficient dietary sulfur, for both the mother and the affected child. A novel contribution is the theory that endothelial nitric oxide synthase produces not only nitric oxide but also sulfate, and that sulfate production is stimulated by sunlight. We further hypothesize that the sulfur shortage manifests as an impaired immune response, including an increased susceptibility to eczema and asthma. Proposed corrective measures involve increased dietary sulfur intake for both the mother and the child, and increased sun exposure. PMID- 22098723 TI - High prevalence of gout with sleep apnea. PMID- 22098724 TI - Adriamycin induced spermatogenesis defect is due to the reduction in epididymal adipose tissue mass: a possible hypothesis. AB - Adriamycin is an anthracycline antibiotic used as anticancer drug since past few decades. Though effective against cancer, it is cardiotoxic, nephrotoxic, hepatotoxic and also toxic for reproductive system. Although a number of potential toxic mechanisms have been identified following exposure to adriamycin, the major pathogenic mechanism appears to be the generation of toxic reactive oxygen species (ROS). Animals treated with adriamycin have shown a decrease in total sperm count. This implies that adriamycin impairs the process of spermatogenesis. Epididymal white adipose tissue (EWAT) is necessary for normal spermatogenesis, and decrease in the EWAT causes disturbance in spermatogenesis. Factor X is an unknown molecule synthesized by EWAT that plays crucial role in spermatogenesis. Adriamycin inhibits Kruppel-like factor 4 (KLF-4) and thus downregulates the adipogenesis process needed to maintain the EWAT mass. Apart form adipocytes, KLF-4 and peroxisome proliferator-activated receptor gamma (PPAR gamma) are also found in spermatogonium and testis, implying its vital role in spermatogenesis. Adriamycin treatment inhibits KLF-4 and thus PPAR-gamma in EWAT and spermatogonium. Reduction of EWAT might cause a decrease in Factor X level. Declining of Factor X level, KLF-4 and PPAR-gamma together will lead to disturbance in spermatogenesis process. PMID- 22098725 TI - Are SCN1A gene mutations responsible for genetic susceptibility to subacute sclerosing panencephalitis? AB - Dravet syndrome, characterized predominantly by myoclonus, has a striking clinical resemblance to subacute sclerosing panencephalitis (SSPE). Patients with Dravet syndrome develop significant mental decline with advancing age of affected child like in SSPE. It is well established that SCN1A gene mutations are associated with Dravet syndrome. Even periodic EEG complexes have been described in Dravet syndrome. In addition to Dravet syndrome, several other types of acute and subacute encephalopathic syndromes having clinical and electroencephalographic resemblance to SSPE are associated with SCN1A gene mutations. SSPE is a devastating progressive inflammatory disorder of the central nervous system. It is caused by persistent infection of the brain by an aberrant measles virus. Only a few of a vast number of measles infected pediatric population develop SSPE. There are several reports describing presence of SSPE is close relatives and it has been described previously in sibling and twin pairs. A genetic susceptibility for development of SSPE is likely. In fact, a variety of genetic abnormalities have already been described in patients with SSPE. It can also be argued that because of striking clinical resemblance between Dravet and various epileptic and encephalopathic syndromes associated with SCN1A gene mutations and SSPE, SCN1A gene abnormalities may also be responsible for susceptibility to SSPE in measles infected children. PMID- 22098726 TI - The patterns of proximal attachments of the popliteus muscle: form and function. AB - The proximal attachments of the popliteus muscle exhibit some variability in the literature, leading to questions regarding function. The anatomic variability of the proximal attachments of popliteus muscles in Thais was studied in order to compare with the previous reported literature by carefully tracking its fibers caudo-cephalically. The sites of the proximal attachments of popliteus muscles found in this study were at the lateral femoral condyle (100%), the posterior horn of the lateral meniscus (63%) and the fibular head (52.1%). Our result also reveals the difference of the strength of the attachment at the lateral meniscus, having some relationship with the attachment at the fibular head, which corresponds with the concept of form and function. PMID- 22098727 TI - Cine-PC MR in assessment of cerebrospinal fluid velocity in the aqueduct of the midbrain correlated with intracranial pressure--initial study. AB - We assessed the changes in cerebrospinal fluid (CSF) hydrodynamics caused by barriers to CSF circulation, and determined the relationship between CSF velocity and intracranial pressure in the aqueduct of the midbrain. This was determined by correlating the CSF peak flow velocity with the intracranial pressure (ICP) obtained from a lumbar puncture (LP) procedure. The CSF peak flow velocity was measured by finger pulse-gated cine-phase contrast (PC) MR scan 8-12 hours after LP was performed in 28 patients. All patients were divided into 2 groups based on the directional patterns of the CSF net flow in the aqueduct of the midbrain over one cardiac cycle. The CSF peak net velocity (V(net)) was then correlated with ICP utilizing Pearson correlation analysis method, with significance difference assigned at the 5% level. Routine MR scanning revealed no abnormal findings in the brain when the direction of the CSF net flow is caudal. V(net) in the aqueduct of the midbrain was correlated positively with ICP (y(V)=0.011+0.002 *(ICP), r=0.69, p<0.01). However, varying degrees of the hydrocephalus were observed in those patients who demonstrated a cranial direction of the CSF net flow. Our results indicate that non-invasive measurement of the CSF peak flow with cine-PC MR imaging can be related to the change of CSF circulation caused by the obstructions to the CSF circulation in the patients with various neurological disorders. This unique method may be a substantially useful tool to assess the changes in the ICP in the directional pattern. PMID- 22098728 TI - Ciprofloxacin as a prophylactic agent against prostate cancer: a "two hit" hypothesis. AB - More evidence indicate that prostate inflammation can lead to prostate cancer development. Prostate cancer affects elderly men. Prostate cancer prophylaxis is an important issue because life expectancy is very long now. Ciprofloxacin is an antibacterial agent used mainly in urinary tract infections and prostate inflammation. This drug acts also against cancer cells by the inhibition of topoisomerase II. These properties should allow it to inhibit the development of prostate cancer. Firstly, ciprofloxacin can stop the acute and chronic prostate inflammation which can lead to cancer development. Secondly, ciprofloxacin can potentially kill prostate cancer cells in their early stage of development. Ciprofloxacin accumulates mainly in the prostate after oral intake thus ciprofloxacin seems to be a perfect candidate as a prophylactic agent. PMID- 22098729 TI - Trafficking coordinate description of intracellular transport control of signaling networks. AB - Many cellular networks rely on the regulated transport of their components to transduce extracellular information into precise intracellular signals. The dynamics of these networks is typically described in terms of compartmentalized chemical reactions. There are many important situations, however, in which the properties of the compartments change continuously in a way that cannot naturally be described by chemical reactions. Here, we develop an approach based on transport along a trafficking coordinate to precisely describe these processes and we apply it explicitly to the TGF-beta signal transduction network, which plays a fundamental role in many diseases and cellular processes. The results of this newly introduced approach accurately capture the distinct TGF-beta signaling dynamics of cells with and without cancerous backgrounds and provide an avenue to predict the effects of chemical perturbations in a way that closely recapitulates the observed cellular behavior. PMID- 22098730 TI - Coding design of positional information for robust morphogenesis. AB - Robust positioning of cells in a tissue against unavoidable noises is important for achieving normal and reproducible morphogenesis. The position in a tissue is represented by morphogen concentrations, and cells read them to recognize their spatial coordinates. From the engineering viewpoint, these positioning processes can be regarded as an information coding. Organisms are conjectured to adopt good coding designs with high reliability for a given number of available morphogen species and their chemical properties. To answer, quantitatively, the questions of how good coding is adopted, and subsequently when, where, and to what extent each morphogen contributes to positioning, we need a way to evaluate the goodness of coding. In this article, by introducing basic concepts of computer science, we mathematically formulate coding processes in morphogen-dependent positioning, and define some key concepts such as encoding, decoding, and positional information and its precision. We demonstrate the best designs for pairs of encoding and decoding rules, and show how those designs can be biologically implemented by using some examples. We also propose a possible procedure of data analysis to validate the coding optimality formulated here. PMID- 22098731 TI - Noise underlies switching behavior of the bacterial flagellum. AB - We report the switching behavior of the full bacterial flagellum system that includes the filament and the motor in wild-type Escherichia coli cells. In sorting the motor behavior by the clockwise bias, we find that the distributions of the clockwise (CW) and counterclockwise (CCW) intervals are either exponential or nonexponential with long tails. At low bias, CW intervals are exponentially distributed and CCW intervals exhibit long tails. At intermediate CW bias (0.5) both CW and CCW intervals are mainly exponentially distributed. A simple model suggests that these two distinct switching behaviors are governed by the presence of signaling noise within the chemotaxis network. Low noise yields exponentially distributed intervals, whereas large noise yields nonexponential behavior with long tails. These drastically different motor statistics may play a role in optimizing bacterial behavior for a wide range of environmental conditions. PMID- 22098732 TI - Native ultrastructure of the red cell cytoskeleton by cryo-electron tomography. AB - Erythrocytes possess a spectrin-based cytoskeleton that provides elasticity and mechanical stability necessary to survive the shear forces within the microvasculature. The architecture of this membrane skeleton and the nature of its intermolecular contacts determine the mechanical properties of the skeleton and confer the characteristic biconcave shape of red cells. We have used cryo electron tomography to evaluate the three-dimensional topology in intact, unexpanded membrane skeletons from mouse erythrocytes frozen in physiological buffer. The tomograms reveal a complex network of spectrin filaments converging at actin-based nodes and a gradual decrease in both the density and the thickness of the network from the center to the edge of the cell. The average contour length of spectrin filaments connecting junctional complexes is 46 +/- 15 nm, indicating that the spectrin heterotetramer in the native membrane skeleton is a fraction of its fully extended length (~190 nm). Higher-order oligomers of spectrin were prevalent, with hexamers and octamers seen between virtually every junctional complex in the network. Based on comparisons with expanded skeletons, we propose that the oligomeric state of spectrin is in a dynamic equilibrium that facilitates remodeling of the network as the cell changes shape in response to shear stress. PMID- 22098733 TI - Quantal regulation and exocytosis of platelet dense-body granules. AB - This study reports how quantal size, or the quantity of chemical messengers within a storage granule, is regulated in platelet dense-body granules via dynamic adaption of granule size according to changing levels of granule contents. Mechanistic studies using carbon-fiber microelectrode fast-scan cyclic voltammetry and amperometry methods correlated with transmission electron microscopy analysis reveal the impact of granule structural changes on granular content secretion kinetics and highlight the dynamic interplay between soluble granule contents and membrane components in exocytosis. Despite the distinct chemical profile of platelet dense-body granules, these secretory granules act according to general biochemical/biophysical phenomena using charge-charge interactions to sequester chemical messengers and employ known conserved exocytotic machinery to deliver them; therefore, the mechanistic information obtained herein further advances the general understanding of exocytosis while revealing fundamental details about blood platelets. PMID- 22098734 TI - Single cell analysis of ligand binding and complex formation of interleukin-4 receptor subunits. AB - Interleukin-4 (IL-4) is an important class I cytokine involved in adaptive immunity. IL-4 binds with high affinity to the single-pass transmembrane receptor IL-4Ralpha. Subsequently, IL-4Ralpha/IL-4 is believed to engage a second receptor chain, either IL-2Rgamma or IL-13Ralpha1, to form type I or II receptor complexes, respectively. This ternary complex formation then triggers downstream signaling via intracellular Janus kinases bound to the cytoplasmic receptor tails. Here, we study the successive steps of complex formation at the single cell level with confocal fluorescence imaging and correlation spectroscopy. We characterize binding and signaling of fluorescently labeled IL-4 by flow cytometry of IL-4-dependent BaF3 cells. The affinity to ectopically expressed IL 4Ralpha was then measured by single-color fluorescence correlation spectroscopy in adherent HEK293T cells that express the components of the type II IL-4R but not type I. Finally, IL-4-induced complex formation was tested by dual-color fluorescence cross-correlation spectroscopy. The data provide evidence for codiffusion of IL-4-A647 bound IL-4Ralpha and the type II subunit IL-13Ralpha1 fused to enhanced green fluorescent protein, whereas type I complexes containing IL-2Rgamma and JAK3 were not detected at the cell surface. This behavior may reflect hitherto undefined differences in the mode of receptor activation between type I (lymphoid) and type II (epithelial) receptor expressing cells. PMID- 22098735 TI - How does stochastic ryanodine receptor-mediated Ca leak fail to initiate a Ca spark? AB - Spontaneous calcium (Ca) sparks are initiated by single ryanodine receptor (RyR) opening. Once one RyR channel opens, it elevates local [Ca] in the cleft space ([Ca](Cleft)), which opens other RyR channels in the same Ca release unit (CaRU) via Ca-induced Ca-release. Experiments by Zima et al. (J. Physiol. 588:4743-4757, 2010) demonstrate that spontaneous Ca sparks occur only when intrasarcoplasmic reticulum (SR) [Ca] ([Ca](SR)) is above a threshold level, but that RyR-mediated SR Ca leak exists without Ca sparks well below this threshold [Ca](SR). We examine here how single RyR opening at lower [Ca](SR) can fail to recruit Ca sparks at a CaRU, while still contributing to SR Ca leak. We assess this using a physiologically detailed mathematical model of junctional SR Ca release in which RyR gating is regulated by [Ca](SR) and [Ca](Cleft). We find that several factors contribute to the failure of Ca sparks as [Ca](SR) declines: 1), lower [Ca](SR) reduces driving force and thus limits local [Ca](Cleft) achieved and the rate of rise during RyR opening; 2), low [Ca](SR) limits RyR open time (tau(O)), which further reduces local [Ca](Cleft) attained; 3), low tau(O) and fast [Ca](Cleft) dissipation after RyR closure shorten the opportunity for neighboring RyR activation; 4), at low [Ca](SR), the RyR exhibits reduced [Ca](Cleft) sensitivity. We conclude that all of these factors conspire to reduce the probability of Ca sparks as [Ca](SR) declines, despite continued RyR-mediated Ca leak. In addition, these same factors explain the much lower efficacy of L-type Ca channel opening to trigger local SR Ca release at low [Ca](SR) during excitation-contraction coupling. Conversely, all of these factors are fundamentally important for increasing the propensity for pro-arrhythmic Ca sparks and waves in cardiac myocytes at high [Ca](SR). PMID- 22098736 TI - Free energy simulations of ligand binding to the aspartate transporter Glt(Ph). AB - Glutamate/Aspartate transporters cotransport three Na(+) and one H(+) ions with the substrate and countertransport one K(+) ion. The binding sites for the substrate and two Na(+) ions have been observed in the crystal structure of the archeal homolog Glt(Ph), while the binding site for the third Na(+) ion has been proposed from computational studies and confirmed by experiments. Here we perform detailed free energy simulations of Glt(Ph), giving a comprehensive characterization of the substrate and ion binding sites, and calculating their binding free energies in various configurations. Our results show unequivocally that the substrate binds after the binding of two Na(+) ions. They also shed light into Asp/Glu selectivity of Glt(Ph), which is not observed in eukaryotic glutamate transporters. PMID- 22098737 TI - GluN1-specific redox effects on the kinetic mechanism of NMDA receptor activation. AB - NMDA receptors are glutamate-activated ion channel complexes central to the functioning of the mammalian nervous system. Opening of the NMDA receptor ion channel pore is initiated by agonist-induced conformational changes in the extracellular ligand-binding domain (LBD) but the dynamic mechanism of this process remains unresolved. We studied how a disulfide bond in the obligatory GluN1 subunit-the sole site of redox modulation in NMDA receptors-controls this activation gating mechanism. This disulfide bond is located in the hinge region of the LBD, and presumably constrains agonist-induced cleft closure of the clamshell-like LBD. Elimination of this bond, by either DTT-mediated reduction or mutagenesis, enhances gating efficiency such that pore opening now occurs with higher frequency and longer duration. The most prominent effect was to shift opening modes to long duration openings reminiscent of a high P(o) gating mode that the NMDA receptor exhibits under ambient oxidizing conditions. In terms of preopen gating steps, elimination of this bond has effects only on the fast gating step consistent with this step being GluN1-specific and reflecting GluN1 gating movements immediately before channel opening. Overall, our results suggest that the dynamics of the GluN1 LBD have strong effects on late pore opening steps including regulating the duration of pore opening. This redox-mediated gating modulation could be an underlying mechanism of NMDA receptor malfunction in redox dependent disease states and presents a potential target of pharmacologic action. PMID- 22098738 TI - Simulations of the alternating access mechanism of the sodium symporter Mhp1. AB - Sodium coupled cotransporters of the five-helix inverted repeat (5HIR) superfamily use an alternating access mechanism to transport a myriad of small molecules across the cell membrane. One of the primary steps in this mechanism is the conformational transition from a state poised to bind extracellular substrates to a state that is competent to deliver substrate to the cytoplasm. Here, we construct a coarse-grained model of the 5HIR benzylhydantoin transporter Mhp1 that incorporates experimental structures of the outward- and inward-open states to investigate the mechanism of this conformational change. Using the weighted ensemble path-sampling method, we rigorously sample the outward- to inward-facing transition path ensemble. The transition path ensemble reveals a heterogeneous set of pathways connecting the two states and identifies two modes of transport: one consistent with a strict alternating access mechanism and another where decoupling of the inner and outer gates causes the transient formation of a continuous permeation pathway through the transporter. We also show that the conformational switch between the outward- and inward-open states results from rigid body motions of the hash motif relative to the substrate bundle, supporting the rocking bundle hypothesis. Finally, our methodology provides the groundwork for more chemically detailed investigations of the alternating mechanism. PMID- 22098739 TI - Tryptophan scanning mutagenesis of the first transmembrane domain of the innexin Shaking-B(Lethal). AB - The channel proteins of gap junctions are encoded by two distinct gene families, connexins, which are exclusive to chordates, and innexins/pannexins, which are found throughout the animal kingdom. Although the relationship between the primary structure and function of the vertebrate connexins has been relatively well studied, there are, to our knowledge, no structure-function analyses of invertebrate innexins. In the first such study, we have used tryptophan scanning to probe the first transmembrane domain (M1) of the Drosophila innexin Shaking B(Lethal), which is a component of rectifying electrical synapses in the Giant Fiber escape neural circuit. Tryptophan was substituted sequentially for 16 amino acids within M1 of Shaking-B(Lethal). Tryptophan insertion at every fourth residue (H27, T31, L35, and S39) disrupted gap junction function. The distribution of these sites is consistent with helical secondary structure and identifies the face of M1 involved in helix-helix interactions. Tryptophan substitution at several sites in M1 altered channel properties in a variety of ways. Changes in sensitivity to transjunctional voltage (Vj) were common and one mutation (S39W) induced sensitivity to transmembrane voltage (Vm). In addition, several mutations induced hemichannel activity. These changes are similar to those observed after substitutions within the transmembrane domains of connexins. PMID- 22098740 TI - Measurement of lipid nanodomain (raft) formation and size in sphingomyelin/POPC/cholesterol vesicles shows TX-100 and transmembrane helices increase domain size by coalescing preexisting nanodomains but do not induce domain formation. AB - Mixtures of unsaturated lipids, sphingolipids, and cholesterol form coexisting liquid-disordered and sphingolipid and cholesterol-rich liquid-ordered (Lo) phases in water. The detergent Triton X-100 does not readily solubilize Lo domains, but does solubilize liquid-disordered domains, and is commonly used to prepare detergent-resistant membranes from cells and model membranes. However, it has been proposed that in membranes with mixtures of sphingomyelin (SM), 1 palmitoyl 2-oleoyl phosphatidylcholine (POPC), and cholesterol Triton X-100 may induce Lo domain formation, and therefore detergent-resistant membranes may not reflect the presence of preexisting domains. To examine this hypothesis, the effect of Triton on Lo domain formation was measured in SM/POPC/cholesterol vesicles. Nitroxide quenching methods that can detect ordered nanodomains with radii >12 A showed that in the absence of Triton X-100 this mixture formed ordered state domains that melt with a midpoint (= T(mid)) at ~45 degrees C. However, T(mid) was lower when detected using various fluorescence resonance energy transfer (FRET) pairs. Furthermore, the T(mid) value was Ro dependent, and decreased as Ro increased. Because FRET can only readily detect domains with radii >Ro, this result can be explained by domain radii that are close to Ro and decrease as temperature increases. An analysis of FRET and quenching data suggests that nanodomain radius gradually decreases from >=150 A to <40 A as temperature increases from 10 to 45 degrees C. Interestingly, the presence of Triton X-100 or a transmembrane-type peptide did not stabilize ordered state formation when detected by nitroxide quenching, i.e., did not increase T(mid). However, FRET-detected T(mid) did increase in the presence of Triton X-100 or a transmembrane peptide, indicating that both increased domain size. Controls showed that the results could not be accounted for by probe-induced perturbations. Thus, SM/POPC/cholesterol, a mixture similar to that in the outer leaflet of plasma membranes, forms nanodomains at physiological temperatures, and TX-100 does not induce domain formation or increase the fraction of the bilayer in the ordered state, although it does increase domain size by coalescing preexisting domains. PMID- 22098741 TI - Membrane-proximal external HIV-1 gp41 motif adapted for destabilizing the highly rigid viral envelope. AB - Electron microscopy structural determinations suggest that the membrane-proximal external region (MPER) of glycoprotein 41 (gp41) may associate with the HIV-1 membrane interface. It is further proposed that MPER-induced disruption and/or deformation of the lipid bilayer ensue during viral fusion. However, it is predicted that the cholesterol content of this membrane (~45 mol %) will act against MPER binding and restructuring activity, in agreement with alternative structural models proposing that the MPER constitutes a gp41 ectodomain component that does not insert into the viral membrane. Here, using MPER-based peptides, we test the hypothesis that cholesterol impedes the membrane association and destabilizing activities of this gp41 domain. To that end, partitioning and leakage assays carried out in lipid vesicles were combined with x-ray reflectivity and grazing-incidence diffraction studies of monolayers. CpreTM, a peptide combining the carboxyterminal MPER sequence with aminoterminal residues of the transmembrane domain, bound and destabilized effectively cholesterol enriched membranes. Accordingly, virion incubation with this peptide inhibited cell infection potently but nonspecifically. Thus, CpreTM seems to mimic the envelope-perturbing function of the MPER domain and displays antiviral activity. As such, we infer that CpreTM bound to cholesterol-enriched membranes would represent a relevant target for anti-HIV-1 immunogen and inhibitor development. PMID- 22098742 TI - A conformational transition in the myosin VI converter contributes to the variable step size. AB - Myosin VI (MVI) is a dimeric molecular motor that translocates backwards on actin filaments with a surprisingly large and variable step size, given its short lever arm. A recent x-ray structure of MVI indicates that the large step size can be explained in part by a novel conformation of the converter subdomain in the prepowerstroke state, in which a 53-residue insert, unique to MVI, reorients the lever arm nearly parallel to the actin filament. To determine whether the existence of the novel converter conformation could contribute to the step-size variability, we used a path-based free-energy simulation tool, the string method, to show that there is a small free-energy difference between the novel converter conformation and the conventional conformation found in other myosins. This result suggests that MVI can bind to actin with the converter in either conformation. Models of MVI/MV chimeric dimers show that the variability in the tilting angle of the lever arm that results from the two converter conformations can lead to step-size variations of ~12 nm. These variations, in combination with other proposed mechanisms, could explain the experimentally determined step-size variability of ~25 nm for wild-type MVI. Mutations to test the findings by experiment are suggested. PMID- 22098743 TI - Millisecond-scale biochemical response to change in strain. AB - Muscle fiber contraction involves the cyclical interaction of myosin cross bridges with actin filaments, linked to hydrolysis of ATP that provides the required energy. We show here the relationship between cross-bridge states, force generation, and Pi release during ramp stretches of active mammalian skeletal muscle fibers at 20 degrees C. The results show that force and Pi release respond quickly to the application of stretch: force rises rapidly, whereas the rate of Pi release decreases abruptly and remains low for the duration of the stretch. These measurements show that biochemical change on the millisecond timescale accompanies the mechanical and structural responses in active muscle fibers. A cross-bridge model is used to simulate the effect of stretch on the distribution of actomyosin cross-bridges, force, and Pi release, with explicit inclusion of ATP, ADP, and Pi in the biochemical states and length-dependence of transitions. In the simulation, stretch causes rapid detachment and reattachment of cross bridges without release of Pi or ATP hydrolysis. PMID- 22098744 TI - Substrate stiffness increases twitch power of neonatal cardiomyocytes in correlation with changes in myofibril structure and intracellular calcium. AB - During neonatal development, there is an increase in myocardial stiffness that coincides with an increase in the contractility of the heart. In vitro assays have shown that substrate stiffness plays a role in regulating the twitch forces produced by immature cardiomyocytes. However, its effect on twitch power is unclear due to difficulties in measuring the twitch velocity of cardiomyocytes. Here, we introduce what we consider a novel approach to quantify twitch power by combining the temporal resolution of optical line scanning with the subcellular force resolution of micropost arrays. Using this approach, twitch power was found to be greater for cells cultured on stiffer posts, despite having lower twitch velocities. The increased power was attributed in part to improved myofibril structure (increased sarcomere length and Z-band width) and intracellular calcium levels. Immunofluorescent staining of alpha-actin revealed that cardiomyocytes had greater sarcomere length and Z-band width when cultured on stiffer arrays. Moreover, the concentration of intracellular calcium at rest and its rise with each twitch contraction was greater for cells on the stiffer posts. Altogether, these findings indicate that cardiomyocytes respond to substrate stiffness with biomechanical and biochemical changes that lead to an increase in cardiac contractility. PMID- 22098745 TI - Nonspecific transcription-factor-DNA binding influences nucleosome occupancy in yeast. AB - Quantitative understanding of the principles regulating nucleosome occupancy on a genome-wide level is a central issue in eukaryotic genomics. Here, we address this question using budding yeast, Saccharomyces cerevisiae, as a model organism. We perform a genome-wide computational analysis of the nonspecific transcription factor (TF)-DNA binding free-energy landscape and compare this landscape with experimentally determined nucleosome-binding preferences. We show that DNA regions with enhanced nonspecific TF-DNA binding are statistically significantly depleted of nucleosomes. We suggest therefore that the competition between TFs with histones for nonspecific binding to genomic sequences might be an important mechanism influencing nucleosome-binding preferences in vivo. We also predict that poly(dA:dT) and poly(dC:dG) tracts represent genomic elements with the strongest propensity for nonspecific TF-DNA binding, thus allowing TFs to outcompete nucleosomes at these elements. Our results suggest that nonspecific TF DNA binding might provide a barrier for statistical positioning of nucleosomes throughout the yeast genome. We predict that the strength of this barrier increases with the concentration of DNA binding proteins in a cell. We discuss the connection of the proposed mechanism with the recently discovered pathway of active nucleosome reconstitution. PMID- 22098746 TI - A theoretical model for the dynamic structure of hepatitis B nucleocapsid. AB - The genomic material of hepatitis B virus (HBV) is confined within a fenestrated nucleocapsid consisting of 240 identical copies of the capsid protein, which has a rigid core and a positively charged and highly flexible C-terminal domain (CTD). Although previous mutagenesis studies have demonstrated the importance of the CTD in viral RNA packaging and reverse transcription, the microscopic structure of the CTD and its interaction with encapsidated nucleic acids at various stages of viral maturation remain poorly understood. Here, we present a theoretical analysis of the radial distributions of the CTD chains and nucleic acids in the hepatitis B virus nucleocapsid at the beginning and final stages of viral reverse transcription based on classical density functional theory and a coarse-gained model for the pertinent biomolecules. We find that a significant portion of the CTD is exposed at the surface of the RNA-containing immature nucleocapsid and that the CTD is mostly confined within the DNA-containing mature nucleocapsid. Large accumulation of cations is predicted inside both immature and mature nucleocapsids. The theoretical results provide new insights into the molecular mechanism of CTD regulation of viral reverse transcription and nucleocapsid trafficking during various stages of the viral replication processes. PMID- 22098747 TI - Experimentally derived structural constraints for amyloid fibrils of wild-type transthyretin. AB - Transthyretin (TTR) is a largely beta-sheet serum protein responsible for transporting thyroxine and vitamin A. TTR is found in amyloid deposits of patients with senile systemic amyloidosis. TTR mutants lead to familial amyloidotic polyneuropathy and familial amyloid cardiomyopathy, with an earlier age of onset. Studies of amyloid fibrils of familial amyloidotic polyneuropathy mutant TTR suggest a structure similar to the native state with only a simple opening of a beta-strand-loop-strand region exposing the two main beta-sheets of the protein for fibril elongation. However, we find that the wild-type TTR sequence forms amyloid fibrils that are considerably different from the previously suggested amyloid structure. Using protease digestion with mass spectrometry, we observe the amyloid core to be primarily composed of the C terminal region, starting around residue 50. Solid-state NMR measurements prove that TTR differs from other pathological amyloids in not having an in-register parallel beta-sheet architecture. We also find that the TTR amyloid is incapable of binding thyroxine as monitored by either isothermal calorimetry or 1,8 anilinonaphthalene sulfonate competition. Taken together, our experiments are consistent with a significantly different configuration of the beta-sheets compared to the previously suggested structure. PMID- 22098748 TI - Spontaneous formation of twisted Abeta(16-22) fibrils in large-scale molecular dynamics simulations. AB - Protein aggregation is associated with fatal neurodegenerative diseases, including Alzheimer's and Parkinson's. Mapping out kinetics along the aggregation pathway could provide valuable insights into the mechanisms that drive oligomerization and fibrillization, but that is beyond the current scope of computational research. Here we trace out the full kinetics of the spontaneous formation of fibrils by 48 Abeta(16-22) peptides, following the trajectories in molecular detail from an initial random configuration to a final configuration of twisted protofilaments with cross-beta-structure. We accomplish this by performing large-scale molecular-dynamics simulations based on an implicit solvent, intermediate-resolution protein model, PRIME20. Structural details such as the intersheet distance, perfectly antiparallel beta-strands, and interdigitating side chains analogous to a steric zipper interface are explained by and in agreement with experiment. Two characteristic fibrillization mechanisms - nucleation/templated growth and oligomeric merging/structural rearrangement - emerge depending on the temperature. PMID- 22098749 TI - Kinetics of nanochain formation in a simplified model of amelogenin biomacromolecules. AB - We show that the kinetics of nanochain formation of amelogenin molecules is well described by a combination of translational and rotational diffusion of a simplified anisotropic bipolar model consisting of hydrophobic spherical colloid particles and a point charge located on each particle surface. The colloid particles interact via a standard depletion attraction whereas the point charges interact through a screened Coulomb repulsion. We study the kinetics via a Brownian dynamics simulation of both translational and rotational motions and show that the anisotropy brought in by the charge dramatically affects the kinetic pathway of cluster formation and our simple model captures the main features of the experimental observations. PMID- 22098750 TI - Assembly of the major light-harvesting complex II in lipid nanodiscs. AB - Self-aggregation of isolated plant light-harvesting complexes (LHCs) upon detergent extraction is associated with fluorescence quenching and is used as an in vitro model to study the photophysical processes of nonphotochemical quenching (NPQ). In the NPQ state, in vivo induced under excess solar light conditions, harmful excitation energy is safely dissipated as heat. To prevent self aggregation and probe the conformations of LHCs in a lipid environment devoid from detergent interactions, we assembled LHCII trimer complexes into lipid nanodiscs consisting of a bilayer lipid matrix surrounded by a membrane scaffold protein (MSP). The LHCII nanodiscs were characterized by fluorescence spectroscopy and found to be in an unquenched, fluorescent state. Remarkably, the absorbance spectra of LHCII in lipid nanodiscs show fine structure in the carotenoid and Q(y) region that is different from unquenched, detergent solubilized LHCII but similar to that of self-aggregated, quenched LHCII in low detergent buffer without magnesium ions. The nanodisc data presented here suggest that 1), LHCII pigment-protein complexes undergo conformational changes upon assembly in nanodiscs that are not correlated with downregulation of its light harvesting function; and 2), these effects can be separated from quenching and aggregation-related phenomena. This will expand our present view of the conformational flexibility of LHCII in different microenvironments. PMID- 22098751 TI - Molecular simulation uncovers the conformational space of the lambda Cro dimer in solution. AB - The significant variation among solved structures of the lambda Cro dimer suggests its flexibility. However, contacts in the crystal lattice could have stabilized a conformation which is unrepresentative of its dominant solution form. Here we report on the conformational space of the Cro dimer in solution using replica exchange molecular dynamics in explicit solvent. The simulated ensemble shows remarkable correlation with available x-ray structures. Network analysis and a free energy surface reveal the predominance of closed and semi open dimers, with a modest barrier separating these two states. The fully open conformation lies higher in free energy, indicating that it requires stabilization by DNA or crystal contacts. Most NMR models are found to be unstable conformations in solution. Intersubunit salt bridging between Arg(4) and Glu(53) during simulation stabilizes closed conformations. Because a semi-open state is among the low-energy conformations sampled in simulation, we propose that Cro-DNA binding may not entail a large conformational change relative to the dominant dimer forms in solution. PMID- 22098752 TI - Improving the physical realism and structural accuracy of protein models by a two step atomic-level energy minimization. AB - Most protein structural prediction algorithms assemble structures as reduced models that represent amino acids by a reduced number of atoms to speed up the conformational search. Building accurate full-atom models from these reduced models is a necessary step toward a detailed function analysis. However, it is difficult to ensure that the atomic models retain the desired global topology while maintaining a sound local atomic geometry because the reduced models often have unphysical local distortions. To address this issue, we developed a new program, called ModRefiner, to construct and refine protein structures from Calpha traces based on a two-step, atomic-level energy minimization. The main chain structures are first constructed from initial Calpha traces and the side chain rotamers are then refined together with the backbone atoms with the use of a composite physics- and knowledge-based force field. We tested the method by performing an atomic structure refinement of 261 proteins with the initial models constructed from both ab initio and template-based structure assemblies. Compared with other state-of-art programs, ModRefiner shows improvements in both global and local structures, which have more accurate side-chain positions, better hydrogen-bonding networks, and fewer atomic overlaps. ModRefiner is freely available at http://zhanglab.ccmb.med.umich.edu/ModRefiner. PMID- 22098753 TI - Subdiffraction-limit study of Kaede diffusion and spatial distribution in live Escherichia coli. AB - Photoactivation localization microscopy (PALM) is used to study the spatial distribution and diffusion of single copies of the protein Kaede in the cytoplasm of live Escherichia coli under moderate growth conditions (67 min doubling time). The spatial distribution of Kaede is uniform within the cytoplasm. The cytoplasmic radius of 380 +/- 30 nm varies little from cell to cell. Single particle tracking using 4 ms exposure times reveals negatively curved plots of mean-square displacement versus time. A detailed comparison with Monte Carlo simulations in a spherocylindrical volume shows that the curvature can be quantitatively understood in terms of free diffusion within a confining volume. The mean diffusion coefficient across cells is = 7.3 +/- 1.1 MUm(2).s( 1), consistent with a homotetrameric form of Kaede. The distribution of squared displacements along the long axis for individual Kaede molecules is consistent with homogeneous diffusion. However, for longer cells, a spatial map of one-step estimates of the diffusion coefficient along x suggests that diffusion is ~20-40% faster within nucleoids than in the ribosome-rich region lying between nucleoid lobes at the cell mid-plane. Fluorescence recovery after photobleaching yielded = 8.3 +/- 1.6 MUm(2).s(-1), in agreement with the single-particle tracking results. PMID- 22098754 TI - Two-color STED microscopy of living synapses using a single laser-beam pair. AB - The advent of superresolution microscopy has opened up new research opportunities into dynamic processes at the nanoscale inside living biological specimens. This is particularly true for synapses, which are very small, highly dynamic, and embedded in brain tissue. Stimulated emission depletion (STED) microscopy, a recently developed laser-scanning technique, has been shown to be well suited for imaging living synapses in brain slices using yellow fluorescent protein as a single label. However, it would be highly desirable to be able to image presynaptic boutons and postsynaptic spines, which together form synapses, using two different fluorophores. As STED microscopy uses separate laser beams for fluorescence excitation and quenching, incorporation of multicolor imaging for STED is more difficult than for conventional light microscopy. Although two-color schemes exist for STED microscopy, these approaches have several drawbacks due to their complexity, cost, and incompatibility with common labeling strategies and fluorophores. Therefore, we set out to develop a straightforward method for two color STED microscopy that permits the use of popular green-yellow fluorescent labels such as green fluorescent protein, yellow fluorescent protein, Alexa Fluor 488, and calcein green. Our new (to our knowledge) method is based on a single excitation/STED laser-beam pair to simultaneously excite and quench pairs of these fluorophores, whose signals can be separated by spectral detection and linear unmixing. We illustrate the potential of this approach by two-color superresolution time-lapse imaging of axonal boutons and dendritic spines in living organotypic brain slices. PMID- 22098755 TI - Replacement of C-terminal histidines uncouples membrane insertion and translocation in diphtheria toxin T-domain. AB - The translocation (T) domain plays a key role in the action of diphtheria toxin and is responsible for transferring the N-terminus-attached catalytic domain across the endosomal membrane into the cytosol in response to acidification. The T-domain undergoes a series of pH-triggered conformational changes that take place in solution and on the membrane interface, and ultimately result in transbilayer insertion and N-terminus translocation. Structure-function studies along this pathway have been hindered because the protein population occupies multiple conformations at the same time. Here we report that replacement of the three C-terminal histidine residues, H322, H323, and H372, in triple-R or triple Q mutants prevents effective translocation of the N-terminus. Introduction of these mutations in the full-length toxin results in decrease of its potency. In the context of isolated T-domain, these mutations cause loss of characteristic conductance in planar bilayers. Surprisingly, these mutations do not affect general folding in solution, protein interaction with the membranes, insertion of the consensus transmembrane helical hairpin TH8-9, or the ability of the T-domain to destabilize vesicles to cause leakage of fluorescent markers. Thus, the C terminal histidine residues are critical for the transition from the inserted intermediate state to the open-channel state in the insertion/translocation pathway of the T-domain. PMID- 22098756 TI - Structural diversity and changes in conformational equilibria of biantennary complex-type N-glycans in water revealed by replica-exchange molecular dynamics simulation. AB - Structural diversity of N-glycans is essential for specific binding to their receptor proteins. To gain insights into structural and dynamic aspects in atomic detail not normally accessible by experiment, we here perform extensive molecular dynamics simulations of N-glycans in solution using the replica-exchange method. The simulations show that five distinct conformers exist in solution for the N glycans with and without bisecting GlcNAc. Importantly, the population sizes of three of the conformers are drastically reduced upon the introduction of bisecting GlcNAc. This is caused by a local hydrogen-bond rearrangement proximal to the bisecting GlcNAc. These simulations show that an N-glycan modification like the bisecting GlcNAc selects a certain "key" (or group of "keys") within the framework of the "bunch of keys" mechanism. Hence, the range of specific glycan protein interactions and affinity changes need to be understood in terms of the structural diversity of glycans and the alteration of conformational equilibria by core modification. PMID- 22098757 TI - The coupled proton transport in the ClC-ec1 Cl(-)/H(+) antiporter. AB - Using a reactive molecular dynamics simulation methodology, the free energy barrier for water-mediated proton transport between the two proton gating residues Glu(203) and Glu(148) in the ClC-ec1 antiporter, including the Grotthuss mechanism of proton hopping, was calculated. Three different chloride-binding states, with 1), both the central and internal Cl(-), 2), the central Cl(-) only, and 3), the internal Cl(-) only, were considered and the coupling to the H(+) transport studied. The results show that both the central and internal Cl(-) are essential for the proton transport from Glu(203) to Glu(148) to have a favorite free energy driving force. The rotation of the Glu(148) side chain was also found to be independent of the internal chloride binding state. These results emphasize the importance of the 2:1 stoichiometry of this well-studied Cl(-)/H(+) antiporter. PMID- 22098758 TI - An active photoreceptor intermediate revealed by in situ photoirradiated solid state NMR spectroscopy. AB - A novel, to our knowledge, in situ photoirradiation system for solid-state NMR measurements is improved and demonstrated to successfully identify the M photointermediate of pharaonis phoborhodopsin (ppR or sensory rhodopsin II), that of the complex with transducer (ppR/pHtrII), and T204A mutant embedded in a model membrane. The (13)C NMR signals from [20-(13)C]retinal-ppR and ppR/pHtrII revealed that multiple M-intermediates with 13-cis, 15-anti retinal configuration coexisted under the continuously photoirradiated condition. NMR signals observed from the photoactivated retinal provide insights into the process of photocycle in the ppR/pHtrII complex. PMID- 22098759 TI - Mechanosensing can result from adhesion molecule dynamics. AB - When plated onto a substrate, cells spread. Many cell types, including smooth muscle cells and fibroblasts, spread more effectively on stiffer substrates, and a simple empirical relationship has been determined that relates a cell's spread area to the substrate stiffness. In addition, some crawling cells when plated onto a stiff substrate will not migrate onto soft substrate, a process called "durotaxis". Here we show that the resistive force predicted previously for dynamic adhesion molecules can account for both of these mechanosensory effects. PMID- 22098760 TI - Endogenous factors modified by hemodialysis may interfere with the accuracy of blood glucose-measuring device. AB - In Japan, self-monitoring of blood glucose (SMBG) devices are widely used both at home and in hospitals, but many analytical errors and safety concerns have been reported about the SMBG devices used in hospitals. Analytical performances of StatStrip (Nova Biomedical Corporation, MA, USA), a new point-of-care testing device and Glutest (Sanwa Chemical, Aichi, Japan), a routinely used SMBG device were compared in glucose measurement of pre- and postdialysis blood samples and we evaluated which factors in blood modified by hemodialysis affect accuracy of these devices. Subjects in this study were 44 hemodialysis patients. Blood samples were obtained from patients just before and just after the hemodialysis. Blood glucose concentrations of samples were measured by StatStrip and Glutest. Hematocrit and plasma concentrations of electrolytes, metabolites, etc. of the samples were measured in the central laboratory. StatStrip showed no difference between pre- and postdialysis blood samples and showed very little bias from reference method. On the other hand, Glutest showed difference between pre- and postdialysis samples. Although there is no problem in the data of predialysis blood samples by Glutest, however, these of the postdialysis blood samples by Glutest were >10% less than reference method. Factors in blood modified by hemodialysis such as hematocrit, uric acid, albumin, potassium, and calcium affected glucose readings by Glutest. Glucose readings by Glutest of samples from hemodialysis patients were affected by hematocrit and several factors, which were modified by hemodialysis. StatStrip is considered as a better device in dialysis hospitals. PMID- 22098761 TI - Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia. AB - INTRODUCTION: We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI). METHODS: Fourteen women with FM (age: 46 +/- 3 years; body mass index (BMI): 26.6 +/- 1.4 kg/m2) and 14 gender-, BMI- (25.4 +/- 1.3 kg/m2), and age-matched (age: 41 +/- 4 years) healthy individuals (CTRL) took part in this cross-sectional study. A treadmill cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve. HR recovery (deltaHRR) was defined as the difference between HR at peak exercise and at both first (deltaHRR1) and second (deltaHRR2) minutes after the exercise test. RESULTS: FM patients presented lower maximal oxygen consumption (VO2 max) when compared with healthy subjects (22 +/- 1 versus CTRL: 32 +/- 2 mL/kg/minute, respectively; P < 0.001). Additionally, FM patients presented lower chronotropic reserve (72.5 +/- 5 versus CTRL: 106.1 +/- 6, P < 0.001), deltaHRR1 (24.5 +/- 3 versus CTRL: 32.6 +/- 2, P = 0.059) and deltaHRR2 (34.3 +/- 4 versus CTRL: 50.8 +/- 3, P = 0.002) than their healthy peers. The prevalence of CI was 57.1% among patients with FM. CONCLUSIONS: Patients with FM who undertook a graded exercise test may present CI and delayed HR recovery, both being indicative of cardiac autonomic impairment and higher risk of cardiovascular events and mortality. PMID- 22098762 TI - Independent genetic loci for sensorimotor gating and attentional performance in BXD recombinant inbred strains. AB - A startle reflex in response to an intense acoustic stimulus is inhibited when a barely detectable pulse precedes the startle stimulus by 30-500 ms. It has been theorized that this phenomenon, named prepulse inhibition (PPI) of a startle response, is an automatic early-stage gating process contributing to the ability to focus attention. Deficits in PPI may therefore contribute to deficits in attentional processing. Both deficits are observed in schizophrenia spectrum disorders. Here, we investigated whether there is overlap in genetic control of PPI and attentional processing phenotypes in the panel of BXD recombinant inbred strains of mice. Using an individually titrated prepulse intensity to handle differences in perceived prepulse intensities among strains, we identified a significant quantitative trait locus (QTL) for PPI at the mid-distal end of chromosome 17. A measure of attentional processing in the five-choice serial reaction time task, response variability, mapped to a different locus on proximal mid chromosome 16. In addition, the estimated genetic and environmental correlations between PPI and several attentional phenotypes were low and not significant. Taken together, the observation of separate genetic loci for PPI and attention and the absence of genetic and environmental correlations indicate that differences in sensorimotor gating do not contribute to differences in attentional performance. Therefore, it is worth pursuing the causative genes residing in both attention and PPI QTL, as these may contribute to separate molecular pathways implicated in neuropsychiatric diseases, such as schizophrenia. PMID- 22098763 TI - Rapid and sensitive hormonal profiling of complex plant samples by liquid chromatography coupled to electrospray ionization tandem mass spectrometry. AB - BACKGROUND: Plant hormones play a pivotal role in several physiological processes during a plant's life cycle, from germination to senescence, and the determination of endogenous concentrations of hormones is essential to elucidate the role of a particular hormone in any physiological process. Availability of a sensitive and rapid method to quantify multiple classes of hormones simultaneously will greatly facilitate the investigation of signaling networks in controlling specific developmental pathways and physiological responses. Due to the presence of hormones at very low concentrations in plant tissues (10-9 M to 10-6 M) and their different chemistries, the development of a high-throughput and comprehensive method for the determination of hormones is challenging. RESULTS: The present work reports a rapid, specific and sensitive method using ultrahigh performance liquid chromatography coupled to electrospray ionization tandem spectrometry (UPLC/ESI-MS/MS) to analyze quantitatively the major hormones found in plant tissues within six minutes, including auxins, cytokinins, gibberellins, abscisic acid, 1-amino-cyclopropane-1-carboxyic acid (the ethylene precursor), jasmonic acid and salicylic acid. Sample preparation, extraction procedures and UPLC-MS/MS conditions were optimized for the determination of all plant hormones and are summarized in a schematic extraction diagram for the analysis of small amounts of plant material without time-consuming additional steps such as purification, sample drying or re-suspension. CONCLUSIONS: This new method is applicable to the analysis of dynamic changes in endogenous concentrations of hormones to study plant developmental processes or plant responses to biotic and abiotic stresses in complex tissues. An example is shown in which a hormone profiling is obtained from leaves of plants exposed to salt stress in the aromatic plant, Rosmarinus officinalis. PMID- 22098764 TI - Association of education level with dialysis outcome. AB - The impact of education on health care outcome has been studied in the past, but its role in the dialysis population is unclear. In this report, we evaluated this association. We used the United States Renal Data System data of end-stage renal disease patients aged 18 years. Education level at the time of end-stage renal disease onset was the primary variable of interest. The outcome of the study was patient mortality. We used four categories of education level: 0 = less than 12 years of education; 1 = high school graduate; 2 = some college; 3 = college graduate. Subgroups based on age, race, sex, donor type, and diabetic status were also analyzed. After adjustments for covariates in the Cox model, using individuals with less than 12 years of education as a reference, patients with college education showed decreased mortality with hazard ratio of 0.81 (95% confidence interval 0.69-0.95), P = 0.010. In conclusion, we showed that higher education level is associated with improved survival of patients on dialysis. PMID- 22098765 TI - Adolescents' risky driving in context. PMID- 22098766 TI - The epidemiology of HIV among young people in sub-Saharan Africa: know your local epidemic and its implications for prevention. AB - BACKGROUND: Broad patterns of HIV epidemiology are frequently used to design generic HIV programs in sub-Saharan Africa. METHODS: We reviewed the epidemiology of HIV among young people in sub-Saharan Africa, and explored the unique dynamics of infection in its different regions. RESULTS: In 2009, HIV prevalence among youth in sub-Saharan Africa was an estimated 1.4% in males and 3.4% in females, but these values mask wide variation at regional and national levels. Within countries there are further major differences in HIV prevalence, such as by sex, urban/rural location, economic status, education, or ethnic group. Within this highly nuanced context, HIV prevention programs targeting youth must consider both where new infections are occurring and where they are coming from. CONCLUSIONS: Given the epidemiology, one-size-fits-all HIV prevention programs are usually inappropriate at regional and national levels. Consideration of local context and risk associated with life transitions, such as leaving school or getting married, is imperative to successful programming for young people. PMID- 22098767 TI - HIV prevention in young people in sub-Saharan Africa: a systematic review. AB - PURPOSE: To systematically review and update evidence on the effectiveness of youth HIV/AIDS prevention interventions in sub-Saharan Africa (SSA) and to make evidence-based policy recommendations to guide efforts toward meeting the United Nations General Assembly Special Session HIV/AIDS goals. METHODS: Recent evidence (January 2005-December 2008) on the effectiveness of interventions to improve reported sexual behavior and biological outcomes among youth in SSA was assessed using the Steady, Ready, Go! (SRG) approach and synthesized with an earlier SRG review (January 1990-June 2005). RESULTS: A total of 23 studies were included following screening of approximately 1,200 citations. School-based, adult-led, curriculum-based interventions showed clear evidence of reducing reported risky sexual behavior. Interventions in health facilities increased the use of services when made accessible and more youth-friendly. In geographically defined communities, both interventions specifically targeting youth and community-wide interventions reduced reports of risky sexual behavior. CONCLUSIONS: HIV prevention among youth is a top priority in SSA. The most promising interventions should be scaled-up now, with careful evaluation, while exploring supplementary interventions to impact HIV incidence. PMID- 22098768 TI - The effect of passengers and risk-taking friends on risky driving and crashes/near crashes among novice teenagers. AB - PURPOSE: The high crash rates of novice teenage drivers are thought to be caused by inexperience and risky driving behavior, exacerbated by passengers, driving at night, and other complex driving conditions. This study examined factors associated with crash/near crash and risky driving rates among novice teenagers, including driving at night versus day, passenger presence and characteristics, and driver psychosocial factors. METHOD: The vehicles of 42 newly licensed teenage drivers were equipped with recording systems that collected data on driving performance and occupant characteristics during their first 18 months of licensure. Survey data were collected at four measurement times. Poisson regression models with random effects were used to analyze crash/near crash and elevated gravitational force event rates (i.e., risky driving); incident rate ratios measured associations with covariates. RESULTS: Crash/near crash rates among novice teenagers were 75% lower in the presence of adult passengers and 96% higher among those teenagers with risky friends. Teenage risky driving was 67% lower with adult passengers, 18% lower with teenage passengers; 20% lower during early night than day; and 109% higher among teens with relatively more risky friends. CONCLUSIONS: The low rate of risky driving in the presence of adult passengers suggests that teens can drive in a less risky manner. The higher rate of risky driving among those with risky friends suggests that risky driving may be socially influenced. PMID- 22098769 TI - An eleven site national quality improvement evaluation of adolescent medicine based eating disorder programs: predictors of weight outcomes at one year and risk adjustment analyses. AB - PURPOSE: This quality improvement project collected and analyzed short-term weight gain data for patients with restrictive eating disorders (EDs) treated in outpatient adolescent medicine-based ED programs nationally. METHODS: Data on presentation and treatment of low-weight ED patients aged 9-21 years presenting in 2006 were retrospectively collected from 11 independent ED programs at intake and at 1-year follow-up. Low-weight was defined as < 90% median body weight (MBW) which is specific to age. Treatment components at each program were analyzed. Risk adjustment was performed for weight gain at 1 year for each site, accounting for clinical variables identified as significant in bivariate analyses. RESULTS: The sites contained 6-51 patients per site (total N = 267); the mean age was 14.1 17.1 years; duration of illness before intake was 5.7-18.6 months; % MBW at intake was 77.5-83.0; and % MBW at follow-up was 88.8-93.8. In general, 40%-63% of low weight ED subjects reached >=90% MBW at 1-year follow-up. At intake, patients with higher % MBW (p = .0002) and shorter duration of illness (p = .01) were more likely to be >=90% MBW at follow-up. Risk-adjusted odds ratios controlled for % MBW and duration of illness were .8 (.5, 1.4)-1.3 (.3, 3.8), with no significant differences among sites. CONCLUSION: A total of 11 ED programs successfully compared quality improvement data. Shorter duration of illness before intake and higher % MBW predicted improved weight outcomes at 1 year. After adjusting for risk factors, program outcomes did not differ significantly. All adolescent medicine-based ED programs were effective in assisting patients to gain weight. PMID- 22098770 TI - Trends in body mass index in adolescence and young adulthood in the United States: 1959-2002. AB - PURPOSE: This study examined trends in body mass index (BMI) during the transition from adolescence to young adulthood by gender and race, using national data from the United States spanning for >40 years from 1959 and 2002. Although past research has investigated BMI trends separately in childhood/adolescence and adulthood, this study uniquely focused on the transition to adulthood (12-26 years) to identify the emergence of the obesity epidemic during this critical life-stage. METHODS: Longitudinal and cross-sectional data were obtained from four nationally representative surveys: National Health and Nutrition Examination Survey, National Longitudinal Study of Adolescent Health, National Health Interview Survey, and National Longitudinal Surveys of Youth (NLSY79 and NLSY97). The analysis tracked age trends in BMI by time, which allowed for the examination of how BMI changed during the transition to adulthood and whether the patterns of change varied by period. Data best suited for trend analysis were identified. Age trends in BMI by gender and race were graphed and regression analysis was used to test for significant differences in the trends using the National Health and Nutrition Examination Survey and National Longitudinal Study of Adolescent Health. RESULTS: BMI increased sharply in the adolescent ages, beginning in the 1990s and among young adults around 2000. This age pattern of BMI increase was more dramatic among females and blacks, particularly black females. CONCLUSIONS: BMI increased during the transition to adulthood and these increases have grown larger over time. Obesity prevention efforts should focus on this high-risk transition period, particularly among minority populations. PMID- 22098771 TI - Acceptability and feasibility of rapid HIV testing in an adolescent clinic setting: youth testing attitudes, knowledge, and behaviors. AB - PURPOSE: To assess youths' attitudes, knowledge, and behaviors regarding rapid HIV testing (RHT) and measure acceptability and feasibility of RHT in an adolescent clinic setting. METHODS: A 2007-2008 project introduced free RHT at an urban, hospital-based adolescent and young adult clinic in Boston, MA. Patients and HIV testing clients were offered either free nonrapid tests or fingerstick RHT. An anonymous questionnaire assessed youths' testing attitudes, knowledge, and behaviors (N = 127). Ordinal logistic regression model was used to determine associations with youth demographic characteristics and testing experience. RESULTS: Most participants valued rapid results. A minority desired confidentiality from parents and insurance providers. Older youth were more likely to know about testing methods (OR: 1.25; CI: 1.04-1.51) and plan for follow-up (OR: 1.43; CI: 1.14-1.81). Age, gender, and race were unrelated to testing facilitators such as rapidity, confidentiality, and cost, although younger clients were more likely to prefer noninvasive methods. Individuals with previous testing experience were more likely to say that they would contribute to expenses and value rapidity over cost. CONCLUSION: There was strong support for RHT among youth receiving HIV testing. Offering RHT to youth may facilitate routine testing. Future research should focus on increasing RHT access among diverse populations of youth. PMID- 22098772 TI - Finding shelter: two-year housing trajectories among homeless youth. AB - PURPOSE: The aim of this study was to (1) identify trajectories of homeless youth remaining sheltered or returning to shelter over a period of 2 years, and (2) to identify predictors of these trajectories. METHOD: A sample of 426 individuals aged 14-24 years receiving services at homeless youth serving agencies completed six assessments over 2 years. Latent class growth analysis was applied to the reports of whether youth had been inconsistently sheltered (i.e., living on the street or in a squat, abandoned building, or automobile) or consistently sheltered (i.e., not living in any of those settings) during the past 3 months. RESULTS: Three trajectories of homeless youth remaining sheltered or returning to shelter were identified: consistently sheltered (approximately 41% of the sample); inconsistently sheltered, short-term (approximately 20%); and inconsistently sheltered, long-term (approximately 39%). Being able to go home and having not left of one's own accord predicted greater likelihood of membership in the short-term versus the long-term inconsistently sheltered trajectory. Younger age, not using drugs other than alcohol or marijuana, less involvement in informal sector activities, being able to go home, and having been homeless for <1 year predicted membership in the consistently sheltered groups versus the long-term inconsistently sheltered groups in the multivariate analyses. CONCLUSIONS: Findings suggest that being able to return home is more important than the degree of individual impairment (e.g., substance use or mental health problems) when determining the likelihood that a homeless youth follows a more or a less chronically homeless pathway. PMID- 22098773 TI - Adolescents with low intelligence are at risk of functional somatic symptoms: the TRAILS study. AB - PURPOSE: Low intelligence is a risk factor for functional somatic symptoms (FSSs) in adults, but it is unknown whether a similar association exists in adolescents. We hypothesized that low intelligence may lead to FSS, and that this association is mediated by low school performance. In addition, we hypothesized that this mediation is particularly present in adolescents who perceive high parental expectations. METHODS: This study was performed in a general population cohort from the TRacking Adolescents' Individual Lives Survey, using data from the first wave (n = 2,230, mean age = 11.09 years, SD = .56, 50.8% girls), second wave (n = 2,149, mean age = 13.65 years, SD = .53, 51.0% girls), and third wave (n = 1,816, mean age = 16.25 years, SD = .72, 53.3% girls). Intelligence was measured using the Wechsler Intelligence Scale for Children-Revised, which resulted in an intelligence quotient (IQ) for each participant. FSSs were measured by the Somatic Complaints Scale of the Youth Self-Report. School performance was assessed by teacher reports and perceived parental expectations by adolescent reports. Structural equation modeling was used to test our hypotheses. RESULTS: We found a significant negative association between IQ and FSS in the whole group (beta = -.24). This association was significant in the group perceiving high parental expectations (beta = -.37), but not in the group perceiving low parental expectations. The association between IQ and FSS was not mediated by school performance. CONCLUSIONS: Low intelligence is associated with a higher predisposition for FSS in adolescents, especially in those adolescents perceiving high parental expectations. PMID- 22098774 TI - Victimization experiences of adolescents in Malaysia. AB - PURPOSE: There has been little community-based research regarding multiple-type victimization experiences of young people in Asia, and none in Malaysia. This study aimed to estimate prevalence, explore gender differences, as well as describe typical perpetrators and family and social risk factors among Malaysian adolescents. METHODS: A cross-sectional survey of 1,870 students was conducted in 20 randomly selected secondary schools in Selangor state (mean age: 16 years; 58.8% female). The questionnaire included items on individual, family, and social background and different types of victimization experiences in childhood. RESULTS: Emotional and physical types of victimization were most common. A significant proportion of adolescents (22.1%) were exposed to more than one type, with 3% reporting all four types. Compared with females, males reported more physical, emotional, and sexual victimization. The excess of sexual victimization among boys was due to higher exposure to noncontact events, whereas prevalence of forced intercourse was equal for both genders (3.0%). Although adult male perpetrators predominate, female adults and peers of both genders also contribute substantially. Low quality of parent-child relationships and poor school and neighborhood environments had the strongest associations with victimization. Family structure (parental divorce, presence of step-parent or single parent, or household size), parental drug use, and rural/urban location were not influential in this sample. CONCLUSION: This study extends the analysis of multiple-type victimization to a Malaysian population. Although some personal, familial, and social factors correlate with those found in western nations, there are cross cultural differences, especially with regard to the nature of sexual violence based on gender and the influence of family structure. PMID- 22098776 TI - Lactococcus lactis subsp. lactis infection in Bester sturgeon, a cultured hybrid of Huso huso * Acipenser ruthenus, in Taiwan. AB - Approximately 5300 hybrid sturgeons with an average body weight of 600-800 g were farmed in 3 round tankers measuring 3m in diameter each containing 28,000 L of aerated groundwater. According to the owner's description, the diseased fish had anorexia, pale body color, and reddish spots on the abdomen. The morbidity and lethality rates in this outbreak were about 70% (3706/5300) and 100% (3706/3706), respectively. The clinical examination revealed enteritis, enlarged abdomen, and rapid respiration rate. The gross findings revealed a volume of about 4 mL of ascites. The histopathological examination showed multiple massive, hemorrhagic or coagulative necrotic foci in the liver and spleen. Furthermore, there was diffuse infiltration of glycogen in hepatic cells, and a few polymorphonuclear and mononuclear leucocytes were observed surrounding the spleen. Some bacterial clumps were noted around the necrotic foci. We also observed that there was moderate to severe, acute, multifocal, coagulative necrosis in the renal parenchyma, with some necrotic foci present beneath the margin of the kidney. Additionally, multifocal, coagulative necrosis was found in the pancreas. Results of microbiologic examinations, including biochemical characteristics, PCR amplification of 16S rRNA gene, sequencing and comparison, and phylogenetic analysis, revealed the pathogen of this infection was Lactococcus lactis subsp. lactis, and based on the results of an antimicrobial agent sensitivity test the bacterium was only sensitive to ampicillin and florfenicol. Additionally, results of in vivo experimental infections in hybrid tilapia showed that 1*10(8) and 1*10(9) CFU/mL of our isolate caused death in all fish and LD(50) values ranged from 10(2) to 10(5) CFU/mL. To the best of the authors' knowledge, this is the first reported case of Lactococcus lactis subsp. lactis infection in hybrid sturgeon. PMID- 22098775 TI - TRENTOOL: a Matlab open source toolbox to analyse information flow in time series data with transfer entropy. AB - BACKGROUND: Transfer entropy (TE) is a measure for the detection of directed interactions. Transfer entropy is an information theoretic implementation of Wiener's principle of observational causality. It offers an approach to the detection of neuronal interactions that is free of an explicit model of the interactions. Hence, it offers the power to analyze linear and nonlinear interactions alike. This allows for example the comprehensive analysis of directed interactions in neural networks at various levels of description. Here we present the open-source MATLAB toolbox TRENTOOL that allows the user to handle the considerable complexity of this measure and to validate the obtained results using non-parametrical statistical testing. We demonstrate the use of the toolbox and the performance of the algorithm on simulated data with nonlinear (quadratic) coupling and on local field potentials (LFP) recorded from the retina and the optic tectum of the turtle (Pseudemys scripta elegans) where a neuronal one-way connection is likely present. RESULTS: In simulated data TE detected information flow in the simulated direction reliably with false positives not exceeding the rates expected under the null hypothesis. In the LFP data we found directed interactions from the retina to the tectum, despite the complicated signal transformations between these stages. No false positive interactions in the reverse directions were detected. CONCLUSIONS: TRENTOOL is an implementation of transfer entropy and mutual information analysis that aims to support the user in the application of this information theoretic measure. TRENTOOL is implemented as a MATLAB toolbox and available under an open source license (GPL v3). For the use with neural data TRENTOOL seamlessly integrates with the popular FieldTrip toolbox. PMID- 22098777 TI - Neuronal regeneration and protection by collagen-binding BDNF in the rat middle cerebral artery occlusion model. AB - It has been well confirmed that brain-derived neurotrophic factor (BDNF) has therapeutic effects following stroke. However, it is difficult to be maintained at a sufficient concentration of BDNF in the infarcted hemisphere. We have shown in our previous work that BDNF fused with a collagen-binding domain (CBD-BDNF) could specifically bind to collagen. The ventricular ependyma of the brain is rich in collagen. Therefore, we have speculated that in the infarcted hemisphere, CBD-BDNF will bind to the collagen of the ventricular ependyma and stimulate the cell proliferation in the subventricular zone (SVZ). Using a rat middle cerebral artery occlusion model (MCAO), we injected CBD-BDNF into the lateral ventricle of MCAO rats. The results demonstrated that CBD-BDNF was retained at high levels in the infarcted hemisphere, promoted neural regeneration and angiogenesis, reduced cell loss, decreased apoptosis, and improved functional recovery. In addition, brain perfusion and metabolism, as evaluated by SPECT and PET, were improved in the CBD-BDNF treated group. PMID- 22098778 TI - Alleviation of rheumatoid arthritis by cell-transducible methotrexate upon transcutaneous delivery. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease that is initiated and maintained by various inflammatory/immune cells and their cytokines, leading to cartilage degradation and bone erosion. Despite its potent therapeutic efficacy on RA, the oral administration of methotrexate (MTX) provokes serious adverse systemic complications, thus necessitating the local application of MTX. Here, we show that transcutaneous MTX (TC-MTX) can efficiently penetrate joint skin ex vivo and in vivo, and that TC-MTX can significantly improve the various inflammatory symptoms associated with RA. Further, TC-MTX preserved the joint structures in mice with collagen-induced arthritis (CIA), which was also confirmed by three-dimensional micro-computed tomography scan. TC-MTX markedly decreased the secretion of inflammatory cytokines both in the serum and in inflamed joints of CIA mice. Further, its therapeutic potential is comparable to that of etanercept, a biological agent that block tumor necrosis factor (TNF) alpha. Importantly, the systemic cytotoxicity of TC-MTX was not detected. Thus, TC-MTX can be a new therapeutic modality for RA patients without systemic complications. PMID- 22098779 TI - Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. AB - Glioblastomas (GBMs) are the most common primary brain tumors with poor prognosis. CD133 has been considered a putative marker of cancer stem cells (CSCs) in malignant cancers, including GBMs. MicroRNAs (miRNAs), highly conserved small RNA molecules, may target oncogenes and have potential as a therapeutic strategy against cancer. However, the role of miRNAs in GBM-associated CSCs remains mostly unclear. In this study, our miRNA/mRNA-microarray and RT-PCR analysis showed that the expression of miR145 (a tumor-suppressive miRNA) is inversely correlated with the levels of Oct4 and Sox2 in GBM-CD133(+) cells and malignant glioma specimens. We demonstrated that miR145 negatively regulates GBM tumorigenesis by targeting Oct4 and Sox2 in GBM-CD133(+). Using polyurethane short branch polyethylenimine (PU-PEI) as a therapeutic-delivery vehicle, PU-PEI mediated miR145 delivery to GBM-CD133(+) significantly inhibited their tumorigenic and CSC-like abilities and facilitated their differentiation into CD133(-)-non-CSCs. Furthermore, PU-PEI-miR145-treated GBM-CD133(+) effectively suppressed the expression of drug-resistance and anti-apoptotic genes and increased the sensitivity of the cells to radiation and temozolomide. Finally, the in vivo delivery of PU-PEI-miR145 alone significantly suppressed tumorigenesis with stemness, and synergistically improved the survival rate when used in combination with radiotherapy and temozolomide in orthotopic GBM-CD133(+) transplanted immunocompromised mice. Therefore, PU-PEI-miR145 is a novel therapeutic approach for malignant brain tumors. PMID- 22098780 TI - Induction of ROS, mitochondrial damage and autophagy in lung epithelial cancer cells by iron oxide nanoparticles. AB - Autophagy has attracted a great deal of research interest in tumor therapy in recent years. An attempt was made in this direction and now we report that iron oxide NPs synthesized by us selectively induce autophagy in cancer cells (A549) and not in normal cells (IMR-90). It was also noteworthy that autophagy correlated with ROS production as well as mitochondrial damage. Protection of NAC against ROS clearly suggested the implication of ROS in hyper-activation of autophagy and cell death. Pre-treatment of cancer cells with 3-MA also exhibited protection against autophagy and promote cellular viability. Results also showed involvement of classical mTOR pathway in autophagy induction by iron oxide NPs in A549 cells. Our results had shown that bare iron oxide NPs are significantly cytotoxic to human cancer cells (A549) but not to the normal human lung fibroblast cells (IMR-90).In other words our nanoparticles selectively kill cancerous cells. It is encouraging to conclude that iron oxide NPs bear the potential of its applications in biomedicine, such as tumor therapy specifically by inducing autophagy mediated cell death of cancer cells. PMID- 22098781 TI - Womens' attitudes and beliefs of childbirth and association with birth preference: a comparison of a Swedish and an Australian sample in mid-pregnancy. AB - BACKGROUND: the rate of caesarean in Australia is twice that of Sweden. Little is known about women's attitudes towards birth in countries where the caesarean rate is high compared to those where normal birth is a more common event. OBJECTIVES: to compare attitudes and beliefs towards birth in a sample of Australian and Swedish women in mid-pregnancy. PARTICIPANTS: women from rural towns in mid Sweden (n=386) and north-eastern Victoria in Australia (n=123). METHODS: questionnaire data was collected from 2007 to 2009. Levels of agreement or disagreement were indicated on sixteen attitude and belief statements regarding birth. Principal components analysis (PCA) identified the presence of subscales within the attitudes inventory. Using these subscales, attitudes associated with preferred mode of birth were determined. Odds ratios were calculated at 95% CI by country of care. RESULTS: the Australian sample was less likely than the Swedish sample to agree that they would like a birth that: 'is as pain free as possible' OR 0.4 (95% CI: 0.2-0.7), 'will reduce my chance of stress incontinence' OR 0.2 (95% CI: 0.1-0.8), 'will least affect my future sex life' OR 0.3 (95% CI: 0.2 0.6), 'will allow me to plan the date when my baby is born' OR 0.4 (95% CI: 0.2 0.7) and 'is as natural as possible' OR 0.4 (95% CI: 0.2-0.9). They were also less likely to agree that: 'if a woman wants to have a caesarean she should be able to have one under any circumstances' OR 0.4 (95% CI: 0.2-0.7) and 'giving birth is a natural process that should not be interfered with unless necessary' OR 0.3 (95% CI: 0.1-0.7). Four attitudinal subscales were found: 'Personal Impact of Birth', 'Birth as Natural Event', 'Freedom of Choice' and 'Safety Concerns'. Women who preferred a caesarean, compared to those who preferred a vaginal birth, across both countries were less likely to think of 'Birth as a natural event'. KEY CONCLUSIONS: the Australian women were less likely than the Swedish women to hold attitudes and beliefs regarding the impact of pregnancy and birth on their body, the right to determine the type of birth they want and to value the natural process of birth. Women from both countries who preferred caesarean were less likely to agree with attitudes related to birth as a natural event. PMID- 22098783 TI - Life cycle assessment of the production and use of polypropylene tree shelters. AB - A detailed Life Cycle Assessment (LCA) has been conducted for the manufacture, use and disposal of polypropylene tree shelters, which are used to protect young seedlings in the first few years of growth. The LCA was conducted using Simapro software, the Ecoinvent database and ReCiPe assessment methodology. Detailed information on materials, manufacturing, packaging and distribution of shelters was obtained from Tubex Ltd. in South Wales, UK. Various scenarios based on different forest establishment methods, with or without tree shelters were derived and analysed using data from published literature and independent sources. The scenarios included commercial forestry in northern temperate conditions, amenity forest establishment in temperate conditions, and forest establishment in semi-arid conditions. For commercial forestry, a reduction in required seedling production and planting as well as additional time-averaged wood production led to significant benefits with tree shelters, both compared to unprotected and fenced cases. For the amenity forest scenarios, tree shelter use had a net environmental impact, while for semi-arid forestry, the benefits of reduction in water use outweighed shelter production impacts. The current practice of in-situ degradation was compared to collection and disposal and it was found that in-situ degradation was slightly preferable in terms of overall environmental impact. Use of biopolymer-based shelters would improve the environmental performance slightly. PMID- 22098782 TI - Haptoglobin genotype predicts development of coronary artery calcification in a prospective cohort of patients with type 1 diabetes. AB - BACKGROUND: Coronary artery disease has been linked with genotypes for haptoglobin (Hp) which modulates extracorpuscular hemoglobin. We hypothesized that the Hp genotype would predict progression of coronary artery calcification (CAC), a marker of subclinical atherosclerosis. METHODS: CAC was measured three times in six years among 436 subjects with type 1 diabetes and 526 control subjects participating in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. Hp typing was performed on plasma samples by polyacrylamide gel electrophoresis. RESULTS: The Hp 2-2 genotype predicted development of significant CAC only in subjects with diabetes who were free of CAC at baseline (OR: 1.95, 95% CI: 1.07-3.56, p = 0.03), compared to those without the Hp 2-2 genotype, controlling for age, sex, blood pressure and HDL-cholesterol. Hp 2 appeared to have an allele-dose effect on development of CAC. Hp genotype did not predict CAC progression in individuals without diabetes. CONCLUSIONS: Hp genotype may aid prediction of accelerated coronary atherosclerosis in subjects with type 1 diabetes. PMID- 22098784 TI - Removal of phthalates from aqueous solution by different adsorbents: a short review. AB - This work presents a short review of adsorptive materials proposed and tested for removing phthalates from an aqueous environment. The objective is not to present an exhaustive review of all the types of adsorbents used, but to focus on selected types of "innovative" materials. Examples include modified activated carbon, chitosan and its modifications, beta-cyclodextrin, and specific types of biomass, such as activated sludge from a wastewater treatment plant, seaweed and microbial cultures. Data from the literature do not confirm the existence of a broad-spectral adsorbent with high sorption efficiency, low production costs and environmentally friendly manufacture. According to the coefficients of Freundlich's isotherm, the most promising adsorbent of those mentioned in this work appears to be the biomass of activated sludge, or extracellular polysaccharides extracted from it. This material benefits from steady production, is cheap and readily available. Nevertheless, before putting it in practice, the treatment and adaptation of this raw material has to be taken into consideration. PMID- 22098785 TI - Thrombolytic therapy for acute ischemic stroke after recent transient ischemic attack. AB - BACKGROUND AND AIM: Safety and efficacy of intravenous thrombolysis in stroke patients with recent transient ischemic attack are hotly debated. Patients suffering transient ischemic attack may present with diffusion-weighted imaging lesions, and although normal computed tomography would not preclude thrombolysis, the concern is that they may be at higher risk for hemorrhage post-thrombolysis treatment. Prior ipsilateral transient ischemic attack might provide protection due to ischemic preconditioning. We assessed post-thrombolysis outcomes in stroke patients who had prior transient ischemic attack. METHODS: Multicentered prospective study of consecutive acute stroke patients treated with intravenous tissue plasminogen activator (tPA). Ipsilateral transient ischemic attack, baseline characteristics, risk factors, etiology, and time-lapse to treatment were recorded. National Institutes of Health Stroke Scale at seven-days and modified Rankin Scale at three-months, symptomatic intracranial hemorrhage, and mortality were compared in patients with and without transient ischemic attack. RESULTS: There were 877 patients included, 60 (6.84%) had previous ipsilateral transient ischemic attack within one-month prior to the current stroke (65% in the previous 24 h). Transient ischemic attack patients were more frequently men (70% vs. 53%; P = 0.011), younger (63 vs. 71 years of age; P = 0.011), smokers (37% vs. 25%; P = 0.043), and with large vessel disease (40% vs. 25%; P = 0.011). Severity of stroke at onset was similar to those with and without prior transient ischemic attack (median National Institutes of Health Stroke Scale score 12 vs. 14 P = 0.134). Those with previous transient ischemic attack were treated earlier (117 +/- 52 vs. 144 +/- 38 mins; P < 0.005). After adjustment for confounding variables, regression analysis showed that previous transient ischemic attack was not associated with differences in stroke outcome such as independence (modified Rankin Scale 0-2) (odds ratios: 1.035 (0.57-1.93) P = 0.91), mortality (odds ratios: 0.99 (0.37-2.67) P = 0.99), or symptomatic intracranial hemorrhage (odds ratios: 2.04 (0.45-9.32) P = 0.36). CONCLUSIONS: Transient ischemic attack preceding ischemic stroke does not appear to have a major influence on outcomes following thrombolysis. Patients with prior ipsilateral transient ischemic attack appear not to be at higher risk of bleeding complications. PMID- 22098786 TI - [Overgrowth with and without obesity: clinical and molecular principles]. AB - Somatic overgrowth is a complex and heterogeneous pathology that is only partially understood, although developments in molecular biology have allowed the discovery of the aetiological basis of some of these conditions. The differential diagnosis of a patient with a possible variant of normality, a chromosomopathy, a dysmorphic syndrome, a metabolic or an endocrine disease is essential. The initial clinical evaluation should include a correct anamnesis and physical examination, as well as complementary laboratory and image analyses that will help to orient the diagnosis. This should include a full blood counts and complete biochemical analysis, determinations of IGF-I, IGFBP-3, free T4, TSH and homocystinuria, as well as a karyotype and an X-ray of the left hand and wrist. These results should be very beneficial in orienting the diagnosis. Additional molecular studies should be performed when a monogenic disease is suspected. Cardiological, ophthalmological, skeletal, psychological and psychiatric studies should be performed if the clinical information and previously mentioned complementary studies so indicate. In this review, the aetiological basis and the diagnostic-therapeutic principles in the most common causes of overgrowth, will be analysed. PMID- 22098787 TI - [Penile cystic lesion after intramuscular testosterone injection]. PMID- 22098788 TI - Uterine artery embolization immediately preceding laparoscopic myomectomy. AB - OBJECTIVE: To determine whether performing uterine artery embolization (UAE) immediately before laparoscopic myomectomy can facilitate a minimally invasive surgical approach for larger uterine fibroids. METHODS: In a retrospective case control study, laparoscopic myomectomy with and without preoperative UAE was examined. Data were analyzed from 26 laparoscopic myomectomies performed by a single surgeon at Northwestern University Feinberg School of Medicine between 2004 and 2010. Controls were matched for age, calendar year, surgeon, and number of fibroids removed. Surgical outcomes included preoperative clinical uterine size, operative time, operative blood loss, and postoperative myoma specimen weight. Data were analyzed via 2-tailed Student t test. RESULTS: Twelve women underwent laparoscopic myomectomy within 169 +/- 16minutes (mean +/- SEM) of preoperative UAE. Fourteen control patients underwent laparoscopic myomectomy alone. The UAE group had a greater mean preoperative clinical uterine size (19.7 versus 12.4 weeks, P<0.001) and a greater mean myoma specimen weight measured postoperatively (595.3 versus 153.6 grams, P<0.05). There were no significant differences in operative time or blood loss, and there were no intra-operative complications. CONCLUSION: UAE performed immediately before laparoscopic myomectomy facilitated minimally invasive surgery for larger uteri and larger uterine myomas, with no differences in operative time or blood loss. PMID- 22098789 TI - Reduced maternal mortality in Tunisia and voluntary commitment to gender-related concerns. AB - OBJECTIVE: To estimate the number and causes of maternal deaths in Tunisia from 1999 to 2007, and compare the results with the last report (1993-1994). METHODS: Data on all deaths of women of reproductive age in the public (1999-2007) and private (2006 only) health sectors were collected and assessed for whether the death was due to pregnancy. Number of live births was provided by the National Institute of Statistics. RESULTS: Mean maternal mortality ratio (MMR) in Tunisia decreased from 68.9 per 100000 live births in 1993-1994 to 36.3 (95% confidence interval, 27.9-46.5) in 2005-2007 (P<0.001). Causes of maternal death did not change significantly during the study period (1999-2007): hemorrhage and hypertensive disorders were the main causes. The gap between urbanized and more rural regions observed in 1993-1994 had narrowed, although MMR remained higher in central and western regions than on the east coast. CONCLUSION: The improvement in MMR can be credited to the voluntary political commitment focused on gender related concerns that has been made in Tunisia, including access to family planning; legalization of abortion; and creation of the National Board for Family and Population, and the Tunisian Safe Motherhood initiative in 1999. PMID- 22098790 TI - Friction-induced whirl vibration: root cause of squeaking in total hip arthroplasty. AB - Squeaking is reported for ceramic-on-ceramic hip arthroplasty, and risk factors leading to this phenomenon have been investigated empirically in the past, this way giving hints to when this phenomenon occurs. The aim of this study is to present an experimentally validated explanation for the dynamical mechanism underlying the squeak, i.e. a description of what happens when noise is generated. First the kinematics of the ceramic bearing couple in relative motion are reconsidered. The relative motion at the contact zone can be understood as superposition of relative rotation and translation. The relative weight of both components depends substantially on the instantaneous load vector, which primarily determines the position of the contact area, and the instantaneous relative rotation vector. For the investigated gait scenarios, both load vector and rotation axis vary strongly during the gait cycle. Second, experimental vibration analysis during squeak is performed. A pronounced micrometer scale elliptical motion of the ball inside the liner is found. It is shown that the rotational component of the relative kinematics during gait indeed leads to friction induced vibrations. We show that a generic whirl type friction induced flutter instability, also known from similar (non bio-) mechanical systems, is the root cause of the emitted squeaking noise. Based on the identified mechanism, the role of THA system parameters (materials, design), patient risk factors, as well as the role of the gait cycle, will have to be reconsidered and linked in the future to develop effective measures against squeaking. PMID- 22098791 TI - Impact of growth hormone hypersecretion on the adult human kidney. AB - Acromegaly is most often secondary to a GH-secreting pituitary adenoma with increased Insulin-like Growth Factor type 1 (IGF-1) level. The consequences of GH/IGF-1 hypersecretion reflect the diversity of action of these hormones. The genes of the GH receptor (GHR), IGF-1, IGF-1 receptor (IGF-1R) and IGF-binding proteins (IGF-BP) are physiologically expressed in the adult kidney, suggesting a potential role of the somatotropic axis on renal structure and functions. The expression of these proteins is highly organized and differs according to the anatomical and functional segments of the nephron suggesting different roles of GH and IGF-1 in these segments. In animals, chronic exposure to high doses of GH induces glomerulosclerosis and increases albuminuria. Studies in patients with GH hypersecretion have identified numerous targets of GH/IGF-1 axis on the kidney: 1) an impact on renal filtration with increased glomerular filtration rate (GFR), 2) a structural impact with an increase in kidney weight and glomerular hypertrophy, and 3) a tubular impact leading to hyperphosphatemia, hypercalciuria and antinatriuretic effects. Despite the increased glomerular filtration rate observed in patients with GH hypersecretion, GH is an inefficient treatment for chronic renal failure. GH and IGF-1 seem to be involved in the physiopathology of diabetic nephropathy; this finding offers the possibility of targeting the GH/IGF 1 axis for the prevention and the treatment of diabetic nephropathy. PMID- 22098792 TI - Methods of verifying the output of the treatment planning system used for high dose rate (HDR) prostate brachytherapy. AB - OBJECTIVES: To investigate the relationships between the planning target volume (PTV) and the total reference air kerma (TRAK) required to irradiate the prostate using the Nucletron microSelection (192)Ir radioactive stepping source afterloader for the treatment of prostate cancer. METHODS: Using 54 patient plans, the relationship between the treatment planning system (TPS) TRAK (TRAK(TPS)) and the estimate and planimetry prostate volumes was investigated. Linear regression analysis was used to predict the TRAK (TRAK(pred)) using the prostate gland height, width and length (HWL) measurements. The TRAK was corrected using a conformal index (COIN) of the plan to improve the accuracy of the model. A further 54 patient plans were then used to evaluate the outcome of the linear regression lines. RESULTS: A formula was proposed (HxWxLxpi/5.19) to estimate the prostate volume, which showed a mean deviation from the planimetry volume of 0.0139 +/- 3.339 cm(3), where 69% was within +/- 10% of planimetry, and 96% within +/-20%. Scatter graphs of TRAK(TPS) for 54 plans, showed a positive linear correlation, r=0.98, using the planimetry volume, and r=0.95 for the estimated volume. The further 54 treatment plans used for evaluation showed the TRAK(pred) was accurately predicted to +/- 10% for 100% of plans using the planimetry volume and 81% using the prostate volume estimate. CONCLUSIONS: The verification method proposed was found to be accurate and independent of TPS parameters, with suitable acceptance margins of +/- 10%. PMID- 22098793 TI - IGRT induced dose burden for a variety of imaging protocols at two different anatomical sites. AB - BACKGROUND AND PURPOSE: Increase in positioning accuracy and treatment adaptation is supported by image guidance. The downside is the concomitant imaging dose. In this study, we report on the total dose picture for different styles of image guidance. MATERIALS AND METHODS: Dose was measured in the Alderson phantom using TLD's. IGRT technology investigated included CBCT at the linac and simulator, multislice-CT and kV and MV planar imaging. Clinically used imaging protocols were applied and the total dose picture was assessed for four different sequences of imaging for a prostate and a head and neck treatment. RESULTS: The different imaging geometries for the various imaging modalities resulted in fairly different dose distributions. Head and neck doses up to 100 mGy and higher were found for portal imaging and multislice-CT. Depending on the IGRT sequence used maximum total dose varies between 120 and 1500 mGy. In prostate maximum doses between 40 and 100 mGy were found for portal imaging and CBCT at the linac. Here the maximum total dose varies between 120 and 2250 mGy depending on the sequence used. DISCUSSION: Factors like patient dimensions, age and sex can influence the applicability of presented values. Careful consideration of imaging dose especially for very intense imaging sequences is recommended. PMID- 22098794 TI - Combined PET/CT image characteristics for radiotherapy tumor response in lung cancer. AB - BACKGROUND AND PURPOSE: Prediction of local failure in radiotherapy patients with non-small cell lung cancer (NSCLC) remains a challenging task. Recent evidence suggests that FDG-PET images can be used to predict outcomes. We investigate an alternative multimodality image-feature approach for predicting post-radiotherapy tumor progression in NSCLC. MATERIAL AND METHODS: We analyzed pre-treatment FDG PET/CT studies of twenty-seven NSCLC patients for local and loco-regional failures. Thirty-two tumor region features based on SUV or HU, intensity-volume histogram (IVH) and texture characteristics were extracted. Statistical analysis was performed using Spearman's correlation (rs) and multivariable logistic regression. RESULTS: For loco-regional recurrence, IVH variables had the highest univariate association. In PET, IVH-slope reached rs=0.3426 (p=0.0403). Motion correction slightly improved correlation of texture features. In CT, coefficient of variation had the highest association rs=-0.2665 (p=0.0871). Similarly for local failure, a CT-IVH parameter reached rs=0.4530 (p=0.0105). For loco-regional and local failures, a 2-parameter model of PET-V(80) and CT-V(70) yielded rs=0.4854 (p=0.0067) and rs=0.5908 (p=0.0013), respectively. Addition of dosimetric variables provided improvement in cases of loco-regional but not local failures. CONCLUSIONS: We proposed a feature-based approach to evaluate radiation tumor response. Our study demonstrates that multimodality image-feature modeling provides better performance compared to existing metrics and holds promise for individualizing radiotherapy planning. PMID- 22098795 TI - Electronic portal images (EPIs) based position verification for the breast simultaneous integrated boost (SIB) technique. AB - BACKGROUND AND PURPOSE: To develop a method based on electronic portal images (EPIs) for the position verification of breast cancer patients that are treated with a simultaneous integrated boost (SIB) technique. METHOD: 3D setup errors of the breast outline and the thoracic wall were determined from EPIs of the tangential treatment fields and anterior posterior (AP) verification field. The method was verified with repeated CT scans of 38 patients with an average setup error larger than 5 mm. RESULT: The 3D position deviation of the boost volume can best be determined from the position deviation of the breast outline in the ventrodorsal direction and the thoracic wall in the lateral and longitudinal directions from the tangential and AP EPIs. The method gives an average overestimation of the deviation of the boost volume in the ventrodorsal, lateral and longitudinal directions by 28%, 20% and 6%, respectively and an average underestimation of the deviation of the whole breast by 32%, 17% and 39%. CONCLUSIONS: The described method is superior to using tangential EPIs only and is recommended for position verification of breast cancer patients that are treated with a SIB technique if no Cone beam CT (CBCT) or fiducial markers can be used. PMID- 22098796 TI - Additional x-ray views increase decision to treat clavicular fractures surgically. AB - BACKGROUND: The trauma series for clavicular fractures includes anterior posterior and 20 degrees cephalic tilt radiographs. Management of clavicular fractures either nonoperatively or operatively is dependent on radiographs. We hypothesized that the interobserver and intraobserver reliability of the treatment decision would be improved with a novel 4-view radiographic series over the standard 2-view radiographic trauma series. METHODS: Four-view radiographic analysis was performed and consisted of anterior-posterior, 20 degrees cephalic tilt, 45 degrees cephalic tilt, and 45 degrees caudal tilt. Radiographs were collected for 50 consecutive patients presenting with acute midshaft clavicular fractures. Four blinded orthopedists were asked to judge whether each case should be treated either operatively or nonoperatively based on the standard 2-view series and then the 4-view series a minimum of 1 week later. This procedure was repeated a minimum of 2 months later. The incidence of surgeon treatment modification was analyzed along with interobserver and intraobserver reliability of both series. RESULTS: In 17 cases, at least 1 surgeon changed the treatment decision between 2- and 4-view review. In 13 cases (26%), the treatment was changed from nonoperative to operative. Significantly greater intraobserver reliability was observed for the 4- versus 2-view series (R = 0.76 and R = 0.64, respectively), with no difference in interobserver reliability (intraclass correlation coefficient of 0.88 and 0.87, respectively). CONCLUSIONS: With the use of a novel 4-view radiographic series that includes orthogonal viewing angles, surgeons are more likely to treat clavicular fractures operatively and their intraobserver reliability is improved, suggesting improved visualization of anterior-posterior displacement. PMID- 22098797 TI - Sinonasal inverted papilloma associated with malignancy: the role of human papillomavirus infection and its implications for radiotherapy. AB - Sinonasal inverted papilloma (IP) is a benign but destructive tumor originating from the ciliated respiratory mucosa of the sinonasal tract. It can be associated with malignancy (squamous cell histology, in particular) and human papillomavirus infection has been investigated as a potential etiological factor linked to malignant alterations of IP. Surgery is the treatment of choice for IP, however, radiotherapy as an adjunct to surgery is indicated for IP with associated malignancy. PMID- 22098798 TI - Adaptation of barley to mild winters: a role for PPDH2. AB - BACKGROUND: Understanding the adaptation of cereals to environmental conditions is one of the key areas in which plant science can contribute to tackling challenges presented by climate change. Temperature and day length are the main environmental regulators of flowering and drivers of adaptation in temperate cereals. The major genes that control flowering time in barley in response to environmental cues are VRNH1, VRNH2, VRNH3, PPDH1, and PPDH2 (candidate gene HvFT3). These genes from the vernalization and photoperiod pathways show complex interactions to promote flowering that are still not understood fully. In particular, PPDH2 function is assumed to be limited to the ability of a short photoperiod to promote flowering. Evidence from the fields of biodiversity, ecogeography, agronomy, and molecular genetics was combined to obtain a more complete overview of the potential role of PPDH2 in environmental adaptation in barley. RESULTS: The dominant PPDH2 allele is represented widely in spring barley cultivars but is found only occasionally in modern winter cultivars that have strong vernalization requirements. However, old landraces from the Iberian Peninsula, which also have a vernalization requirement, possess this allele at a much higher frequency than modern winter barley cultivars. Under field conditions in which the vernalization requirement of winter cultivars is not satisfied, the dominant PPDH2 allele promotes flowering, even under increasing photoperiods above 12 h. This hypothesis was supported by expression analysis of vernalization responsive genotypes. When the dominant allele of PPDH2 was expressed, this was associated with enhanced levels of VRNH1 and VRNH3 expression. Expression of these two genes is needed for the induction of flowering. Therefore, both in the field and under controlled conditions, PPDH2 has an effect of promotion of flowering. CONCLUSIONS: The dominant, ancestral, allele of PPDH2 is prevalent in southern European barley germplasm. The presence of the dominant allele is associated with early expression of VRNH1 and early flowering. We propose that PPDH2 promotes flowering of winter cultivars under all non-inductive conditions, i.e. under short days or long days in plants that have not satisfied their vernalization requirement. This mechanism is indicated to be a component of an adaptation syndrome of barley to Mediterranean conditions. PMID- 22098799 TI - Obesity: overview of an epidemic. AB - The obesity epidemic in the United States has proven difficult to reverse. We have not been successful in helping people sustain the eating and physical activity patterns that are needed to maintain a healthy body weight. There is growing recognition that we will not be able to sustain healthy lifestyles until we are able to address the environment and culture that currently support unhealthy lifestyles. Addressing obesity requires an understanding of energy balance. From an energy balance approach it should be easier to prevent obesity than to reverse it. Further, from an energy balance point of view, it may not be possible to solve the problem by focusing on food alone. Currently, energy requirements of much of the population may be below the level of energy intake than can reasonably be maintained over time. Many initiatives are underway to revise how we build our communities, the ways we produce and market our foods, and the ways we inadvertently promote sedentary behavior. Efforts are underway to prevent obesity in schools, worksites, and communities. It is probably too early to evaluate these efforts, but there have been no large-scale successes in preventing obesity to date. There is reason to be optimistic about dealing with obesity. We have successfully addressed many previous threats to public health. It was probably inconceivable in the 1950s to think that major public health initiatives could have such a dramatic effect on reducing the prevalence of smoking in the United States. Yet, this serious problem was addressed via a combination of strategies involving public health, economics, political advocacy, behavioral change, and environmental change. Similarly, Americans have been persuaded to use seat belts and recycle, addressing two other challenges to public health. But, there is also reason to be pessimistic. Certainly, we can learn from our previous efforts for social change, but we must realize that our challenge with obesity may be greater. In the other examples cited, we had clear goals in mind. Our goals were to stop smoking, increase the use of seatbelts, and increase recycling. The difficulty of achieving these goals should not be minimized, but they were clear and simple goals. In the case of obesity, there is no clear agreement about goals. Moreover, experts do not agree on which strategies should be implemented on a widespread basis to achieve the behavioral changes in the population needed to reverse the high prevalence rates of obesity. We need a successful model that will help us understand what to do to address obesity. A good example is the recent HEALTHY study. This comprehensive intervention was implemented in several schools and aimed to reduce obesity by concentrating on behavior and environment. This intervention delivered most of the strategies we believe to be effective in schools. Although the program produced a reduction in obesity, this reduction was not greater than the reduction seen in the control schools that did not receive the intervention. This does not mean we should not be intervening in schools, but rather that it may require concerted efforts across behavioral settings to reduce obesity. Although we need successful models, there is a great deal of urgency in responding to the obesity epidemic. An excellent example is the effort to get menu labeling in restaurants, which is moving rapidly toward being national policy. The evaluation of this strategy is still ongoing, and it is not clear what impact it will have on obesity rates. We should be encouraging efforts like this, but we must evaluate them rigorously. Once we become serious about addressing obesity, it will likely take decades to reverse obesity rates to levels seen 30 years ago. Meanwhile, the prevalence of overweight and obesity remains high and quite likely will continue to increase. PMID- 22098801 TI - Obesity, psychiatric status, and psychiatric medications. AB - This article has shown that obesity is related to several psychiatric disorders, the most thoroughly researched of which is depression. In both community and clinical populations, the observed relationship is more consistent in women than in men, and is stronger in more severely obese individuals. The presence of BED also is associated with elevated risk of additional psychopathology. Longitudinal research provides evidence to support a pathway from obesity to depression, as well as one from depression to obesity. Weight loss, particularly with nonpharmacologic methods, appears to have favorable group-level effects on mood, but may be associated with adverse outcomes for some individuals. Persons who require antipsychotic medications are at risk for weight gain and metabolic abnormalities, and their management should be informed by consensus guidelines. PMID- 22098800 TI - Regulation of energy balance and body weight by the brain: a distributed system prone to disruption. AB - Maintaining adequate energy supply via regulation of food intake and energy expenditure is crucial for survival and reproduction. The neural control of energy balance is highly complex, occurs across distributed central and peripheral areas, and incorporates multiple domains of control (including homeostatic and hedonic processes). The sheer number of active compounds (such as leptin and GLP-1) involved in the regulation of food intake speaks to the redundancy and complexity of the system. The balance between energy intake and expenditure is under CNS control. Constant bidirectional communication between the brain and the GI tract, as well as between the brain and other relevant tissues (ie, adipose tissue, pancreas, and liver), ensures that the brain constantly perceives and responds accordingly to the energy status/needs of the body. This elegant biological system is subject to disruption by a toxic obesogenic environment, leading to syndromes such as leptin and insulin resistance, and ultimately further exposing obese individuals to further weight gain and T2DM. Recent imaging studies in humans are beginning to examine the influence that higher-order/hedonic brain regions have on homeostatic areas, as well as their responsiveness to homeostatic peripheral signals. With greater understanding of these mechanisms, the field moves closer to understanding and eventually treating the causalities of obesity. PMID- 22098802 TI - Eating disorders and obesity. AB - In conclusion, 2 types of disordered eating behaviors affect some overweight and obese persons. BED and NES present an excellent opportunity to recognize, treat, and prevent these disorders that, at the least, maintain, and at worst, promote, overweight and obesity. Articles in this volume by Wilson and co-workers and Allison and colleagues discuss current treatment options for BED and NES, respectively. Clinicians are encouraged to evaluate the presence of BED and NES in all patients who seek treatment for their obesity. Although the prevalence of these 2 eating disorders is relatively low, both are associated with significant distress and dysfunction that can be ameliorated with effective treatment. PMID- 22098803 TI - Treatment of binge eating disorder. AB - The two specialty psychological therapies of CBT and IPT remain the treatments of choice for the full range of BED patients, particularly those with high levels of specific eating disorder psychopathology such as overvaluation of body shape and weight. They produce the greatest degree of remission from binge eating as well as improvement in specific eating disorder psychopathology and associated general psychopathology such as depression. The CBT protocol evaluated in the research summarized above was the original manual from Fairburn and colleagues. Fairburn has subsequently developed a more elaborate and sophisticated form of treatment, namely, enhanced CBT (CBT-E) for eating disorders. Initial research suggests that CBT-E may be more effective than the earlier version with bulimia nervosa and Eating Disorder Not Otherwise Specified patients. CBT-E has yet to be evaluated for the treatment of BED, although it would currently be the recommended form of CBT. Of relevance in this regard is that the so-called broad form of the new protocol includes 3 optional treatment modules that could be used to address more complex psychopathology in BED patients. One of the modules targeted at interpersonal difficulties is IPT, as described earlier in this chapter. Thus, the broader protocol could represent a combination of the two currently most effective therapies for BED. Whether this combined treatment proves more effective than either of the components alone, particularly for a subset of BED patients with more complex psychopathology, remains to be tested. CBT-E also includes a module designed to address what Fairburn terms "mood intolerance" (problems in coping with negative affect) that can trigger binge eating and purging. The content and strategies of this mood intolerance module overlap with the emotional regulation and distress tolerance skills training of Linehan's dialectical behavior therapy (DBT). Two randomized controlled trials have tested the efficacy of an adaptation of DBT for the treatment of BED (DBT-BED) featuring mindfulness, emotion regulation, and distress tolerance training. A small study by Telch and colleagues found that modified DBT-BED was more effective than a wait list control in eliminating binge eating. A second study showed that DBT-BED resulted in a significantly greater remission rate from binge eating at posttreatment than a group comparison treatment designed to control for nonspecific therapeutic factors such as treatment alliance and expectations.50 This difference between the two treatments disappeared over a 12-month follow-up, indicating the absence of DBT-BED-specific influences on long-term outcomes. Both CBT and IPT have been shown to be more effective in eliminating binge eating than BWL in controlled, comparative clinical trials. Nonetheless, BWL has been effective in reducing binge eating and associated eating problems in BED patients in some studies and might be suitable for treatment of BED patients without high levels of specific eating disorder psychopathology. A finding worthy of future research is the apparent predictive value of early treatment response to BWL, indicating when BWL is likely to prove effective or not. No evidence supports the concern that BWL's emphasis on moderate caloric restriction either triggers or exacerbates binge eating in individuals with BED. Initially, CBTgsh was recommended as a feasible first-line treatment that might be sufficient treatment for a limited subset of patients in a stepped care approach. More recent research, however, has shown that CBTgsh seems to be as effective as a specialty therapy, such as IPT, with a majority of BED patients. The subset of patients that did not respond well to CBTgsh in this research were those with a high level of specific eating disorder psychopathology, as noted. A plausible explanation for this moderator effect is that the original Fairburn CBTgsh manual does not include an explicit emphasis on body shape and weight concerns. Subsequent implementation of this treatment has incorporated a module that directly addresses overvaluation of body shape and weight. Future research should determine whether an expanded form of CBTgsh is suitable for the full range of patients with BED. CBTgsh is recommended as a treatment for BED on two other counts. First, its brief and focused nature makes it cost effective. Second, its structured format makes it more readily disseminable than other longer, multicomponent psychological therapies. It can be implemented by a wider range of treatment providers than more technically complex, time-consuming, and clinical expertise-demanding specialty therapies such as CBT-E and IPT. The latter evidence-based therapies are rarely available to patients with BED in routine clinical care settings. Nevertheless, it must be noted that much of the research on CBTgsh to date has been conducted in an eating disorder specialty clinic setting. The degree to which the treatment can be adapted to a range of clinical service settings remains to be determined. In addition, little is known about the specific provider qualifications and level of expertise required to implement CBTgsh successfully. Despite its brief and focal nature, specific provider skills regarding what and what not to address in treatment are required. Currently available pharmacologic treatments cannot be recommended for treatment of BED. Aside from the inconsistent results of existing studies, the striking absence of controlled long-term evaluation of such treatment argues against its use.As summarized, the evidence-based treatments of CBT, IPT, and CBTgsh result in significant improvement and large treatment effects on multiple outcome measures aside from binge eating in overweight and obese patients. These include specific eating disorder psychopathology (eg, overvaluation of body shape and weight), general psychopathology (eg, depression), and psychosocial functioning. Moreover, these changes are typically well-maintained over 1 to 2 years of follow-up. The exception to this profile of improvement remains weight loss and its maintenance over time. These specialty psychological treatments do not produce weight loss, although successfully eliminating binge eating might protect against future weight gain. BWL consistently produces short-term weight loss, the extent of which has varied across different studies. Long-term weight loss has yet to be demonstrated, however. In this regard, the findings with obese patients with BED are not different than those on the treatment of obesity in general, in which there is little robust evidence of enduring weight loss effects of BWL. PMID- 22098804 TI - Treatment of night eating syndrome. AB - Although treatment research for NES remains limited, several options are available for patients whose symptoms require clinical attention. Pharmacotherapy has received the most empirical support of the proposed treatments. Controlled trials are needed to confirm the initial results from pilot studies with CBT, behavioral therapy, and phototherapy, and an extended controlled trial of progressive muscle relaxation would be useful. In their comprehensive review of the field, Striegel-Moore and colleagues have questioned the clinical utility of NES as a diagnostic entity and stress the very limited nature of treatment studies to date. Research in this field has to provide a systematic examination of the approaches described here, as well as others yet to be identified. This pursuit seems warranted given that persons suffering with the cluster of symptoms identified as NES are approaching health care providers for relief and are often frustrated by the lack of recognition of this syndrome. Future studies should test a wider variety of medications that would target serotonin or the circadian timing of eating. Additionally, trials comparing and combining medication treatments and CBT (or progressive muscle relaxation alone) would also be useful in addressing which treatment should be used as a first line treatment. With NES being considered for inclusion as a Feeding and Eating Condition Not Elsewhere Classified (FEC-NEC) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, it is likely that more clinical attention and studies will address these important issues in the coming years. PMID- 22098805 TI - Medical and behavioral evaluation of patients with obesity. AB - Obesity may be the most significant medical problem that health care providers will face over the coming decades. Physicians must aggressively address this chronic disease, providing both preventive and therapeutic care. Since this topic has not been traditionally taught in medical school or residency training, physicians and other health providers will need to acquire the knowledge, skills, and attitudes necessary to be effective obesity care providers. Performing a detailed initial assessment, including an obesity focused history, physical examination, and selected laboratory and diagnostic tests is fundamental to the process of care. PMID- 22098806 TI - Dietary approaches to the treatment of obesity. AB - Various dietary strategies can effectively reduce weight, as shown by this review. Those that are coupled with behavior therapy and ongoing support tend to produce longer lasting effects. Improvements in health parameters are observed with each dietary strategy. Improvements in diabetes and CVD risk factors have been observed with diets ranging from 10% fat to 45% fat. HP diets seem to be particularly effective in reducing fat mass and TAG, especially in individuals with dyslipidemia and who are at risk for type 2 diabetes. Likewise, LC diets have been shown to be effective in decreasing TAG and VLDL and increasing HDL. Although low-GI diets do not seem to be superior to any other diet for weight loss, there is evidence to suggest that they may provide some metabolic benefit for those with type 2 diabetes. Clearly, all of these diets have benefits but they can be realized only when they are followed. A common theme across studies is poor long-term adherence and weight regain. Dansinger and colleagues found a strong association between diet adherence and clinically significant weight loss, suggesting that "sustained adherence to a diet" rather than "following a certain type of diet" is the key to successful weight management. PMID- 22098807 TI - Obesity and physical activity. AB - Physical activity seems to be an important component of lifestyle interventions for weight loss and maintenance. Although the effects of physical activity on weight loss may seem to be modest, there seems to be a dose-response relationship between physical activity and weight loss. Physical activity also seems to be a critically important behavior to promote long-term weight loss and the prevention of weight regain. The benefits of physical activity on weight loss are also observed in patients with severe obesity (BMI >= 35 kg/m2) and in patients who have undergone bariatric surgery. Moreover, independent of the effect of physical activity on body weight, engagement in physical activity that results in improved cardiorespiratory fitness can contribute to reductions in health risk in overweight and obese adults. Thus, progression of overweight and obese patients to an adequate dose of physical activity needs to be incorporated into clinical interventions for weight control. PMID- 22098809 TI - Motivational interviewing for weight loss. AB - MI is a patient-centered directive counseling style that aims to facilitate patients' likelihood of making behavior change through the exploration and strengthening of personal motivations. Hallmarks of MI include a collaborative relationship between patient and practitioner, a focus on the elicitation and enhancement of change talk, a nonconfrontational style, and a concerted effort to minimize resistance. MI has been applied to a variety of health-related behaviors, and a growing body of research suggests that this approach may be useful in the context of behavioral weight management. Although results are not uniform, the majority of research suggests that MI delivered as an independent component in addition to a behavioral weight loss program can augment weight loss and likely exerts its beneficial effects through enhancement of treatment engagement and adherence to behavioral recommendations. Furthermore, preliminary research suggests that MI may be helpful in promoting weight maintenance after an initial loss has been achieved. Given that behavioral weight management is a relatively new application of MI, a variety of issues merit further investigation. Of particular interest are issues related to the type and extent of provider training necessary to ensure adequate skill development, cost effectiveness of MI, and translational research to determine the feasibility and effectiveness of incorporating MI strategies into real-world weight loss settings. PMID- 22098808 TI - Behavioral treatment of obesity. AB - This review has shown that behavioral treatment is effective in inducing a 10% weight loss, which is sufficient to significantly improve health. Weight loss maintenance is challenging for most patients. Long-term outcomes have the potential to be improved through various methods including prolonging contact between patients and providers (either in the clinic or via Internet or telephone), facilitating high amounts of physical activity, or combining lifestyle modification with pharmacotherapy. Innovative programs also are being developed to disseminate behavioral approaches beyond traditional academic settings. PMID- 22098810 TI - Drug treatment of obesity. AB - Both diet and medications are useful in the treatment of the obese patient. Weight loss of about 10% below baseline can be achieved with both, and there is no evidence that the composition of the diet, by itself, has any influence on weight loss. Presently only 1 drug is approved for long-term treatment of overweight patients, and its effectiveness is limited to palliation of the chronic disease of obesity. Combinations of medications and antidiabetic drugs that produce weight loss are being evaluated. PMID- 22098811 TI - Surgical treatments for obesity. AB - Bariatric surgery is currently the most effective and durable treatment option for extreme obesity. Restrictive procedures, such as AGB and SG, limit gastric capacity and, thus, food intake while leaving the gastrointestinal tract intact. Malabsorptive procedures, such as BPD, shorten the length of the intestine to decrease nutrient absorption. Combined procedures, such as RYGB, include restriction and gastrointestinal rearrangement. Procedures that bypass segments of the gut are associated with greater weight loss and greater improvements in comorbid conditions than is gastric banding. This may be due, in part, to the differential effects of gastrointestinal rearrangement on the secretion of orexigenic and anorexigenic gut peptides that regulate appetite, glucose homeostasis, and body weight. Bariatric surgery is generally associated with low rates of perioperative and postoperative morbidity and mortality, although rigorous comparative safety data are lacking. High-quality, long-term, randomized, controlled trials are needed to compare the efficacy, safety, and cost effectiveness of the various bariatric surgery procedures with each other, as well as with intensive nonsurgical weight loss interventions. PMID- 22098812 TI - Obesity: a public health approach. AB - Obesity is an epidemic that likely will worsen without substantive changes to the current environment. Although treatment of the individual has conventionally been the focus of the obesity field, prevention using a public health model will be essential for making progress on a population level. There are encouraging signs that communities across the country are acknowledging the complex causes of obesity and making impressive reforms to improve their health and that of their children. Public policy changes long have been used to combat infectious and chronic diseases and will be vital in the attempt to reduce the toll of poor diet, physical inactivity, and obesity. PMID- 22098813 TI - Preface. Obesity and associated eating disorders: a guide for mental health professionals. PMID- 22098814 TI - Monitoring and blunting styles in fluid restriction consultation. AB - Excessive fluid overload is common in hemodialysis patients. Understanding fluid intake behavior in relation to used cognitive coping style would serve the fluid restriction consultation. The aim of this study was to explore whether hemodialysis patients' fluid intake behavior differs as a function of used coping style. Secondary analysis of data from 51 hemodialysis patients regarding cognitive coping style (assessed by the Threatening Medical Situations Inventory) and fluid intake behavior were used. The participants' mean age was 62.9 years (range 27-84), they had received dialysis treatment for 3.9 years on average (range 0-22), 63% were male and they had gained 3.6% (+/-1.3) of their dry body weight during the interdialytic period. There was a significant difference in fluid intake behavior between coping groups (F = 3.899, d.f. 2, P = 0.027). The difference (P = 0.028) was isolated between patients with cognitive blunting style and patients with neutral coping style. Identification of hemodialysis patients using cognitive avoidance strategies can be advantageous in renal care. Fluid advice provided may have to be adjusted to the used coping style, especially for patients with a blunting coping style. However, the findings need to be confirmed, and the effect of individualized counseling needs to be evaluated in forthcoming studies. PMID- 22098815 TI - Tracheobronchial malposition of fine bore feeding tube in patients with mechanical ventilation. PMID- 22098816 TI - Serological testing of cattle experimentally infected with Mycoplasma mycoides subsp. mycoides Small Colony using four different tests reveals a variety of seroconversion patterns. AB - BACKGROUND: To study the specific antibody response to infection with Mycoplasma mycoides subsp. mycoides Small Colony (MmmSC), the agent of Contagious Bovine Pleuropneumonia (CBPP), we examined three panels of sera collected during three experimental infection trials in African cattle. The methods used included an in house complement fixation test (CFT), a commercially available CFT, a competitive antibody ELISA (cELISA) and the immunoblotting test (IBT). In addition, lung tissue samples were examined by culture. RESULTS: A total of 89% (51/59) of all experimentally infected animals tested positive on at least one of the serological tests throughout the trial. The specific antibody titres to the MmmSC infection became positive first by CFT (6 to 9 days post infection [dpi]), followed by IBT (9 to 13 dpi) and cELISA (13 to 16 dpi). Individual animals were found to display remarkably distinct seroconversion patterns, which allowed their classification into i) early high responders, ii) late high responders, and iii) low responders. In accordance with other studies, none of the present serological tests was capable of detecting all CBPP infected animals. CONCLUSION: Comparison of the assays' performance in terms of sensitivity and specificity raises serious questions as to their reliability for identification of infected individuals in the field. In view of these limitations, a combination of CFT and cELISA can markedly improve CBPP diagnosis at single-animal level. PMID- 22098818 TI - A tribute. PMID- 22098817 TI - Biliary dysplasia in patients with primary sclerosing cholangitis: additional value of DNA ploidity. AB - BACKGROUND: Detection of biliary dysplasia in PSC is essential for proper timing of liver transplantation to prevent the development of cholangiocancer, which is considered a contraindication for liver transplantation in most centres. In patients with PSC, differential diagnosis of benign, premalignant and malignant biliary strictures is difficult. AIMS: This prospective study aimed to evaluate the role of DNA analysis in combination with brush cytology, scored ERCP findings, and tumour markers to detect hepatobiliary dysplasia and malignancy. MATERIAL AND METHODS: Brush samples for cytology and for evaluation of DNA content analysed with flow cytometry came from 102 consecutive PSC patients referred for ERCP. Symptoms, serum Ca19-9 and CEA were determined at the time of index biliary examination. ERCP findings were scored for intra- and extrahepatic changes. The end-points were liver transplantation or diagnosis of malignancy or dysplasia. RESULTS: Most of the patients were asymptomatic at the time of ERCP: 73% had no symptoms, and 12% had only mild symptoms. An aneuploid DNA content was evident in 20 (20%) patients, and cells suspected for malignancy in 22 (21%). Seven patients had both aneuploidity and cytology (7%) suspicious for malignancy. An end-point, diagnosis of malignancy or liver transplantation was achieved in 42 patients. Combining DNA ploidity and cytology in patients at the end-point, sensitivity was 72%, specificity 82%, positive predictive value 86% and negative predictive value 67%. DISCUSSION AND CONCLUSION: In this mostly asymptomatic PSC patient population, 33% demonstrated abnormal brush cytology or aneuploidity. Determining DNA ploidy and brush cytology during ERCP offers a useful tool for identifying those PSC patients who are at high risk of developing cholangiocancer. PMID- 22098819 TI - Introduction and transition. PMID- 22098820 TI - Letter to the editor. PMID- 22098821 TI - New-onset psoriasis in a maintenance hemodialysis patient. AB - New-onset psoriasis is extremely rare in hemodialysis (HD) patients, and several trials of dialysis therapies (HD and peritoneal dialysis) in psoriasis have indicated remarkable improvement in skin lesions and well-being even in patients without renal impairment. We describe a patient who developed severe psoriasis despite undergoing chronic maintenance hemodialysis for 5 years and was treated successfully with oral cyclosporin A. PMID- 22098822 TI - Detection of porcine DNA in gelatine and gelatine-containing processed food products-Halal/Kosher authentication. AB - A commercially available real-time PCR, based on a multi-copy target cytochrome b (cyt b) using porcine specific primers, has been validated for the Halal/Kosher authentication of gelatine. Extraction and purification of DNA from gelatine were successfully achieved using the SureFood(r) PREP Animal system, and real-time PCR was carried out using SureFood(r) Animal ID Pork Sens kit. The minimum level of adulteration that could be detected was 1.0% w/w for marshmallows and gum drops. A small survey was undertaken of processed food products such as gum drops, marshmallows and Turkish delight, believed to contain gelatine. Of fourteen food products from Germany, two samples were found to contain porcine gelatine, whereas of twenty-nine samples from Turkey twenty-eight were negative. However, one product from Turkey contained porcine DNA and thus was not Halal, and neither was the use of porcine gelatine indicated on the product label. PMID- 22098823 TI - Preliminary study on the effect of caspase-6 and calpain inhibitors on postmortem proteolysis of myofibrillar proteins in chicken breast muscle. AB - The objective was to determine the effect of three different protease inhibitors, caspase-6 specific inhibitor VEID-CHO (N-Acetyl-Val-Glu-Ile-Asp-al), calpain inhibitor leupeptin or calpain inhibitor EGTA on protein degradation, ultrastructure of myofibrils and calpain activity during postmortem (PM) aging of chicken muscle. Results showed that proteolysis of nebulin, troponin-T and desmin during 14-days postmortem storage were inhibited significantly by leupeptin. Inhibitive effects of VEID-CHO and EGTA on these protein degradations were significant only during 1-day postmortem storage. The activities of calpains were inhibited noticeably by leupeptin and EGTA, but not by VEID-CHO. Samples treated with VEID-CHO, leupeptin and EGTA retarded structural disruption of chicken muscle fibers. These results demonstrate that calpain is a major contributor to PM tenderization; while caspase-6 plays, if any, a minimal role in the conversion of chicken muscle to meat. PMID- 22098824 TI - Abnormal muscle activation during gait in diabetes patients with and without neuropathy. AB - The World Health Organization warns that, in 2000, as many as 33 million Europeans suffered from diabetes, approximately 15% will likely develop foot ulcers, and approximately 15-20% of these patients will face lower-extremity amputation. Changes in some gait parameters that appear to be specific in diabetes have been identified in the literature: shorter stride length, reduced walking speed, and altered lower limb and trunk mobility. The present study aimed at evaluating the role of altered muscle activity in gait alterations of diabetic subjects with and without neuropathy. This study involved 50 subjects: 10 controls (BMI 24.4 +/- 2.8, age 61.2 +/- 5.07), 20 diabetics (BMI 26.4 +/- 2.5, age 56.53 +/- 13.29) and 20 neuropathics (BMI 26.8 +/- 3.4, age 61.2 +/- 7.7). The electrical activity of six muscles was collected bilaterally on the lower limb during gait: gluteus medius, rectus femoris, tibialis anterior, peroneous longus, gastrocnemius lateralis, and extensor digitorum communis. Electromyographic activity was represented through linear envelopes. Time and space parameters were also evaluated by means of two Bertec force plates and a six cameras motion capture system (BTS, 60-120 Hz). At initial contact and loading response, an early peak of rectus femoris activity occurred in diabetic subjects with and without neuropathy. During midstance a delay of gastrocnemius activity was observed in diabetic non-neuropathic subjects. During terminal swing a delay of rectus femoris and gluteus medius activity was seen in diabetic non neuropathic subjects'. The results suggest that important muscle activity deviations are present in diabetic subjects although these are not directly related to neuropathy. PMID- 22098825 TI - Both coordination and symmetry of arm swing are reduced in Parkinson's disease. AB - OBJECTIVE: A recent study reporting significantly reduced symmetry in arm swing amplitude in early Parkinson's disease (PD), as measured during single strides in a gait laboratory, led to this investigation of arm swing symmetry and coordination over many strides using wearable accelerometers in PD. METHODS: Forearm accelerations were recorded while eight early PD subjects and eight Controls performed 8-min walking trials. Arm swing asymmetry (ASA), maximal cross correlation (MXC), and instantaneous relative phase (IRP) of bilateral arm swing were compared between PD and Controls. Correlations between arm swing measurements (ASA and MXC) and Unified PD Rating Scale (UPDRS) scores were estimated. RESULTS: PD subjects demonstrated significantly higher ASA (p=0.002) and lower MXC (p<0.001) than Controls. The IRP probability distribution for PD was significantly different than Controls (p<0.001), with an angular standard deviation of 67.2 degrees for PD and 50.6 degrees for Controls. Among PD subjects, ASA was significantly correlated with the UPDRS score for the limbs (R(2)=0.58, p=0.049), whereas MXC was significantly correlated with the tremor subscore of the limbs (R(2)=0.64, p=0.031). DISCUSSION: The study confirms previously reported higher arm swing asymmetry in PD but also shows there is significantly lower MXC and greater IRP variability, suggesting that reduction in bilateral arm coordination may contribute to clinically observed asymmetry in PD. The differential correlation of clinical measures of motor disability with measurements of arm swing during gait is intriguing and deserves further investigation. PMID- 22098826 TI - [Foreword]. PMID- 22098828 TI - Gastric cancer: endoscopic diagnosis and staging. AB - Gastric cancer is common and is a cause of severe morbidity and mortality. Early diagnosis can improve the chances of cure and prolong survival because prognosis is inversely related to the disease stage. Endoscopy plays an important role in diagnosis. Emerging adjunct technologies such as image-enhanced endoscopy and magnification endoscopy aid in early cancer detection. Endoscopic ultrasonography is an additional useful tool for preoperative staging. Endoscopy for screening, except for high-risk patients, and outside areas of high prevalence, remains controversial. PMID- 22098827 TI - [Neurological adverse events under anti-TNF alpha therapy]. AB - INTRODUCTION: Anti-TNF alpha treatments are increasingly prescribed in various rheumatological or gastroenterological inflammatory diseases. Several adverse events, including neurological episodes have been reported in the literature. Relation to treatment is a major concern and guidelines for management of those patients are not available. The aim of our study is to collect and analyze neurological adverse events occurring during anti-TNF alpha therapy, and to propose guidelines for diagnosis of demyelinating-induced diseases. METHODS: All patients treated with anti-TNF alpha drug, who were addressed in our department following a neurological event, were collected. We gathered clinical data including previous neurological history and immunosuppressive treatments. Paraclinical data included brain and spinal MRI, CSF study and outcome after anti TNF therapy was collected. RESULTS: Nine patients were included in this study. Sex ratio was eight and mean age was 49+/-9 years. One patient had previous history of subarachnoidian hemorrage. All the patients previously received immunosuppressive drugs, including methotrexate (nine) and leflunomide (four). Three patients had a brain MRI before initiation of anti-TNF treatment, which was normal. Clinical episode was stroke-like in three cases, clinically isolated syndrome (CIS) in five cases, and peripheral neuropathy in one case. MRI showed lesions suggestive of demyelinating T2 hyperintensities in four cases, vascular infarcts in two cases, and non-specific T2 hyperintensities in three cases. Barkhof and Tintore criteria were fulfilled in one of the four CIS cases. CSF study was available for six patients. It was normal (four cases), showed oligoclonal bands (one case) and lymphocytic meningitis (one case). Anti-TNF alpha discontinuation was decided in five cases. Outcome was favorable for eight patients. One patient, whom MRI fulfilled Barkhof and Tintore criteria, and CSF showed oligoclonal bands, further developed relapsing remitting multiple sclerosis. CONCLUSION: Our study is compatible with data found in the literature. Barkhof and Tintore criteria and CSF study are useful in clinical practice to diagnose a first demyelinating event. Standardized paraclinical neurological explorations should be proposed to physicians who are in charge of anti-TNF treated patients. PMID- 22098829 TI - Gastrointestinal stromal tumors of the stomach. AB - Gastrointestinal stromal tumors (GISTs) are relatively rare mesenchymal tumors located within the submucosa of the GI tract. The defining characteristic of GISTs is the presence of the cell-surface antigen CD117 receptor tyrosine kinase, identified by immunohistochemistry. Currently the only cure for GIST is complete surgical resection. Imatinib has revolutionized the treatment of GISTs and has been used as adjuvant treatment after resection, and as treatment for locally advanced, recurrent, and metastatic GIST. Imatinib resistance has become a significant concern in the treatment of GISTs and other tyrosine kinase inhibitors that target different pathways are currently being studied. PMID- 22098830 TI - Familial gastric cancer: genetics, diagnosis, and management. AB - This article focuses on the diagnosis and management of familial gastric cancer, particularly hereditary diffuse gastric cancer (HDGC). First, existing consensus guidelines are discussed and then the pathology and genetics of HDGC are reviewed. Second, patient management is covered, including surveillance gastroscopy, prophylactic total gastrectomy, and management of the risk of breast cancer. PMID- 22098831 TI - Standard D2 and modified nodal dissection for gastric adenocarcinoma. AB - The quality of surgical treatment is a major determinant of cancer treatment outcomes; however, controlling surgical quality is a difficult task. Surgical treatment of gastric cancers, and especially the benefits of nodal dissection, has been a topic of debate and no consensus has been reached to date. The D2 nodal dissection defined, standardized, and practiced in Japan is a technically challenging procedure but carries better locoregional disease control. This article reviews the current definition of D1, D1 plus, and D2 nodal dissections, as well as the nodal dissection technique, indications for its modification, and the learning curve. PMID- 22098832 TI - Gastric cancer eastern experience. AB - Several guidelines are used for cancer therapy throughout the world. The Japan Gastric Cancer Association guideline, whereby standard surgery for T2 to T4 curable gastric cancer is defined as more than two-thirds gastrectomy with D2 dissection, are widely followed, with further data being gathered from either single institutions or nationwide registry. In the East, D2 dissection shows much better results than less extended surgery followed by adjuvant treatment. Adjuvant chemotherapy without radiotherapy shows significantly better survival results than surgery alone only when D2 dissection is applied. Without good local control, including regional lymph node metastasis, the cure rate cannot be high. PMID- 22098833 TI - Surgery for gastric cancer: what the trials indicate. AB - To optimize the therapeutic value of an operation for cancer, surgeons must weigh survival value against mortality/morbidity risk. As a result of several prospective, randomized trials, many surgeons feel that international opinion has reached a consensus. Reflexively radical surgical hubris has certainly given way to a more nuanced, customized approach to this disease. But issues remain. This article critically reviews existing data and emphasizes areas of continued controversy. PMID- 22098834 TI - Preoperative and postoperative chemotherapy for gastric cancer. AB - Radical surgery offers the only chance of cure for patients with operable gastric cancer; however, outcomes remain generally poor due to a high rate of relapse post gastric surgery. Multimodality therapy using chemotherapy, radiation or a combination of both have been evaluated in different parts of the world to improve outcomes from surgery alone. Perioperative chemotherapy is generally preferred in Europe in contrast to postoperative chemoradiation in the US or adjuvant fluoropyrimidine chemotherapy in East Asia. Regardless of these variations, systemic chemotherapy consistently results in a survival benefit when used in multimodality treatment of operable gastric cancer. PMID- 22098835 TI - Phase I and II clinical trials for gastric cancer. AB - Gastric cancer remains a global public health problem with considerable heterogeneity in pathogenesis and clinical presentation across geographic regions. Improved understanding of the molecular biology of this disease has opened avenues for targeted intervention. An individualized treatment approach is required for optimal management of this cancer. Overcoming resistance to therapy requires combining targeted agents with the traditional options of chemotherapy/radiation therapy, and also targeting more than 1 pathway of carcinogenesis at a time. Encouraging molecular hypothesis and biomarker-driven trials will lead to improved patient outcomes and may eventually enable the therapeutic nihilism associated with gastric cancer to be overcome. PMID- 22098836 TI - Endoscopic mucosal resection, endoscopic submucosal dissection, and beyond: full layer resection for gastric cancer with nonexposure technique (CLEAN-NET). AB - Mucosal cancer in the gastrointestinal tract generally has low risk of lymph node metastasis. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are techniques of local excision of neoplasia confined to the mucosal layer. Specimens from EMR/ESD contribute to several diagnoses, and histologic results affect treatment decisions. A combined laparoscopic and endoscopic approach to neoplasia with a nonexposure technique allows full thickness resection of the stomach wall without exposing the gastric lumen to the peritoneal cavity, preventing cancer cell dissemination to the peritoneal cavity. This article reviews EMR/ESD and describes a new full-thickness resection method using the nonexposure technique (CLEAN-NET). PMID- 22098837 TI - Laparoscopic resection for gastric carcinoma: Western experience. AB - There has been much speculation regarding differences in outcome for patients who have gastric cancer in the Eastern versus Western world. Among other factors, these differences have contributed to a unique cohort of patients and experience in the Western staging/evaluation of gastric cancer and in the application of minimally invasive approaches for treatment. This review summarizes the current state of laparoscopic approaches for the staging and treatment of gastric adenocarcinoma for patients presenting in Western countries, with their associated unique presentation, comorbidities, and outcomes. PMID- 22098838 TI - Molecular markers for incidence, prognosis, and response to therapy. AB - Lung cancer is the most common malignancy in the United States and worldwide. In 2011, it is estimated that more than 221,000 people in the United States will be diagnosed with cancer of the lung and bronchus. For patients with early-stage disease, 5-year survival approaches only 50%. Recent advances using molecular, genetic, and proteomic profiling of lung tumors have enabled refining the prognosis for patients with non-small cell lung cancer. With targeted therapies, there is an opportunity to enhance long-term survival. This article discusses several key molecular markers used in the prognostication and treatment of non small cell lung cancer. PMID- 22098839 TI - Management of gastric cancer. Foreword. PMID- 22098840 TI - Management of gastric cancer. Preface. PMID- 22098841 TI - Politics and patient care. PMID- 22098842 TI - CRASH-2 goes viral. PMID- 22098843 TI - Breast cancer: old and new debates. PMID- 22098844 TI - The Global Fund: getting the reforms right. PMID- 22098846 TI - Effect of population-based screening on breast cancer mortality. PMID- 22098850 TI - Hydroxycarbamide use in young children with sickle-cell anaemia. PMID- 22098851 TI - Hydroxycarbamide use in young children with sickle-cell anaemia. PMID- 22098852 TI - Need to realign patient-oriented and commercial and academic research. PMID- 22098853 TI - MRI for breast cancer screening, diagnosis, and treatment. AB - MRI is used widely both for screening women who are at increased risk of breast cancer and for treatment selection. Prospective studies confirm that MRI screening of women with known or suspected genetic mutation results in a higher sensitivity for cancer detection than does mammography. However, survival data are not available. In women with breast cancer, MRI detects cancer not identified with other types of screening. In two randomised trials, this increased sensitivity did not translate into improved selection of surgical treatment or a reduction in the number of operations. Data for longer-term outcomes such as ipsilateral breast tumour recurrence rates and contralateral breast cancer incidence are scarce, but to date do not show clear benefit for MRI. MRI is better than other methods of assessing the response to neoadjuvant chemotherapy, and is helpful in identifying the primary tumour in patients who present with axillary adenopathy. PMID- 22098854 TI - Gene expression profiling in breast cancer: classification, prognostication, and prediction. AB - Microarray-based gene expression profiling has had a major effect on our understanding of breast cancer. Breast cancer is now perceived as a heterogeneous group of different diseases characterised by distinct molecular aberrations, rather than one disease with varying histological features and clinical behaviour. Gene expression profiling studies have shown that oestrogen-receptor (ER)-positive and ER-negative breast cancers are distinct diseases at the transcriptomic level, that additional molecular subtypes might exist within these groups, and that the prognosis of patients with ER-positive disease is largely determined by the expression of proliferation-related genes. On the basis of these principles, a molecular classification system and prognostic multigene classifiers based on microarrays or derivative technologies have been developed and are being tested in randomised clinical trials and incorporated into clinical practice. In this review, we focus on the conceptual effect and potential clinical use of the molecular classification of breast cancer, and discuss prognostic and predictive multigene predictors. PMID- 22098855 TI - A strange case of waitress headache. PMID- 22098856 TI - Non-communicable diseases and surgery at the UN? "Fugetaboutit!". PMID- 22098857 TI - The forgotten psychosocial dimension of the obesity epidemic. PMID- 22098858 TI - Nonlinearities in soft tissue strain. PMID- 22098859 TI - Characterization of the nonlinear behaviour and the failure of human liver capsule through inflation tests. AB - This paper aims at describing an inflation test protocol on a human liver capsule using stereo-correlation. The biaxial tension created by the inflation test is comparable to the type of loading the capsule would be subjected to during a liver compression. Confocal microscopy associated to an anti-collagen coloration reveals that the tissue is isotropic at the meso-scale. Stereo-correlation provides the strain field of the capsule during the test. It emphasizes the boundary condition effects on the strain field. The measurement of the shape of the capsule is used to determine the parameters of two hyperelastic (polynomial and exponential) homogeneous models. The ultimate first principal strain before failure is measured locally and its value is 50.5%+/-10.8%. In this protocol, the light goes throughout the sample and makes the heterogeneities of the material appear as darker grey levels on the pictures. These heterogeneities also appear on the strain fields, so we can assume that they have different material properties. PMID- 22098860 TI - Modeling failure of soft anisotropic materials with application to arteries. AB - The arterial wall is a composite where the preferred orientation of collagen fibers induces anisotropy. Though the hyperelastic theories of fiber-reinforced composites reached a high level of sophistication and showed a reasonable correspondence with the available experimental data they are short of the failure description. Following the tradition of strength of materials the failure criteria are usually separated from stress analysis. In the present work we incorporate a failure description in the hyperelastic models of soft anisotropic materials by introducing energy limiters in the strain energy functions. The limiters provide the saturation value for the strain energy which indicates the maximum energy that can be stored and dissipated by an infinitesimal material volume. By using some popular constitutive models enhanced with the energy limiters we analyze rupture of a sheet of arterial material under the plane stress state varying from the uniaxial to equal biaxial tension. We calculate the local failure criteria including the maximum principal stress, the maximum principal stretch, the von Mises stress, and the strain energy at the moment of the sheet rupture. We find that the local failure criterion in the form of the critical strain energy is the most robust among the considered ones. We also find that the tensile strength-the maximum principal stress-that is usually obtained in uniaxial tension tests might not be appropriate as a failure indicator in the cases of the developed biaxiality of the stress-strain state. PMID- 22098861 TI - Mechanical events within the arterial wall under the forces of pulsatile flow: a review. AB - Under the dynamic conditions of pulsatile flow, the forces exerted by the fluid on the vessel wall create considerable displacements and stresses within the thickness of the vessel wall. We review a series of analytical options for exploring the dynamics of the vessel wall, specifically displacements and stresses within the depth of the vessel wall, under a range of conditions including the degree of external tethering and the mechanical consistency of the wall material. It is shown that one of the most important effects of tethering is that of drastically restricting radial displacements of and within the vessel wall. This restriction in turn places limits on the length and speed of the propagating wave. Specifically, the wave speed is significantly reduced as a result of tethering. This has important consequences because the wave speed, or pulse wave velocity as it is referred to in the clinical setting, is used as an index of vascular stiffening in relation to aging or age related hypertension. It is found further that the extent of displacements and shear stresses within the vessel wall depend critically on the relative proportions of viscous and elastic content within the wall. In particular, loss of viscous consistency leads to higher shear stresses within the wall, thus putting higher loading on elastin and may ultimately lead to elastin fatigue. As elastin gradually fails, its load bearing function is presumably taken over by collagen which renders the vessel wall less elastic and more rigid as is observed in the aging process. PMID- 22098862 TI - Anisotropic time-dependant behaviour of the aortic valve. AB - The complex tri-layered structure of the aortic valve (AV) results in anisotropic quasi-static mechanical behaviour. However, its influence on AV viscoelasticity remains poorly understood. Viscoelasticity may strongly influence AV dynamic mechanical behaviour, making it essential to characterise the time-dependent response for designing successful substitutes. This study attempts to characterise the time-dependent behaviour of the AV at different strain and load increments, and to gain insight into the contribution of the microstructure to this behaviour. Uniaxial incremental stress-relaxation and creep experiments were undertaken, and the experimental data analysed with a generalised Maxwell model, to determine the characteristic time-dependent parameters. Results showed that the time dependent response of the tissue differed with the loading direction, and also with the level of applied load or strain, in both stress-relaxation and creep phenomena. Both phenomena were consistently more pronounced in the radial loading direction. Fitting of the Maxwell model highlighted that the time dependent modes required to model the data also varied in different increments, and additionally with the loading direction. These results suggest that different micro-structural mechanisms may be activated in stress-relaxation and creep, determined by the microstructural organisation of the valve matrix in each loading direction, at each strain or load increment. PMID- 22098864 TI - A systems based experimental approach to tactile friction. AB - This work focuses on the friction in contacts where the human finger pad is one of the interacting surfaces. This 'tactile friction' requires a full understanding of the contact mechanics and the behaviour of human skin. The coefficient of friction cannot be considered as a property of the skin alone, but depends on the entire tribo-system. In this work, frictional forces were measured using a commercially available load cell. Parameters such as the hydration of the skin, the normal load on the contact and the roughness of the contacting surfaces were varied, whilst keeping the other parameters constant. The tests were performed under controlled environmental conditions. The total friction force is a combination of forces related to adhesion and to deformation. A commonly made assumption is that, to describe the friction of human skin, the deformation component can be ignored and only the adhesive behaviour has to be taken into account. However, in this study it was found that the forces related to the (micro-scale) deformation of skin can have a significant contribution to the total friction force; this is valid both for dry conditions and in the presence of water, when hydration of the skin causes softening. PMID- 22098863 TI - Effect of orientation and targeted extracellular matrix degradation on the shear mechanical properties of the annulus fibrosus. AB - The intervertebral disc experiences combinations of compression, torsion, and bending that subject the disc substructures, particularly the annulus fibrosus (AF), to multidirectional loads and deformations. Combined tensile and shear loading is a particularly important loading paradigm, as compressive loads place the AF in circumferential hoop tension, and spine torsion or bending induces AF shear. Yet the anisotropy of AF mechanical properties in shear, as well as important structure-function mechanisms governing this response, are not well understood. The objective of this study, therefore, was to investigate the effects of tissue orientation and enzymatic degradation of glycosaminoglycan (GAG) and elastin on AF shear mechanical properties. Significant anisotropy was found: the circumferential shear modulus, Gthetaz, was an order of magnitude greater than the radial shear modulus, Grtheta. In the circumferential direction, prestrain significantly increased the shear modulus, suggesting an important role for collagen fiber stretch in shear properties for this orientation. While not significant and highly variable, ChABC treatment to remove GAG increased the circumferential shear modulus compared to PBS control (p=0.15). Together with the established literature for tensile loading of fiber-reinforced GAG-rich tissues, the trends for changes in shear modulus with ChABC treatment reflect complex, structure-function relationships between GAG and collagen that potentially occur over several hierarchical scales. Elastase digestion did not significantly affect shear modulus with respect to PBS control; further contributing to the notion that circumferential shear modulus is dominated by collagen fiber stretch. The results of this study highlight the complexity of the structure-function relationships that govern the mechanical response of the AF in radial and circumferential shear, and provide new and more accurate data for the validation of material models and tissue-engineered disc replacements. PMID- 22098866 TI - A mesostructurally-based anisotropic continuum model for biological soft tissues- decoupled invariant formulation. AB - Characterising and modelling the mechanical behaviour of biological soft tissues is an essential step in the development of predictive computational models to assist research for a wide range of applications in medicine, biology, tissue engineering, pharmaceutics, consumer goods, cosmetics, transport or military. It is therefore critical to develop constitutive models that can capture particular rheological mechanisms operating at specific length scales so that these models are adapted for their intended applications. Here, a novel mesoscopically-based decoupled invariant-based continuum constitutive framework for transversely isotropic and orthotropic biological soft tissues is developed. A notable feature of the formulation is the full decoupling of shear interactions. The constitutive model is based on a combination of the framework proposed by Lu and Zhang [Lu, J., Zhang, L., 2005. Physically motivated invariant formulation for transversely isotropic hyperelasticity. International Journal of Solids and Structures 42, 6015-6031] and the entropic mechanics of tropocollagen molecules and collagen assemblies. One of the key aspects of the formulation is to use physically-based nanoscopic quantities that could be extracted from experiments and/or atomistic/molecular dynamics simulations to inform the macroscopic constitutive behaviour. This effectively couples the material properties at different levels of the multi-scale hierarchical structure of collagenous tissues. The orthotropic hyperelastic model was shown to reproduce very well the experimental multi-axial properties of rabbit skin. A new insight into the shear response of a skin sample subjected to a simulated indentation test was obtained using numerical direct sensitivity analyses. PMID- 22098865 TI - Fiber angle and aspect ratio influence the shear mechanics of oriented electrospun nanofibrous scaffolds. AB - Fibrocartilages, including the knee meniscus and the annulus fibrosus (AF) of the intervertebral disc, play critical mechanical roles in load transmission across joints and their function is dependent upon well-defined structural hierarchies, organization, and composition. All, however, are compromised in the pathologic transformations associated with tissue degeneration. Tissue engineering strategies that address these key features, for example, aligned nanofibrous scaffolds seeded with mesenchymal stem cells (MSCs), represent a promising approach for the regeneration of these fibrous structures. While such engineered constructs can replicate native tissue structure and uniaxial tensile properties, the multidirectional loading encountered by these tissues in vivo necessitates that they function adequately in other loading modalities as well, including shear. As previous findings have shown that native tissue tensile and shear properties are dependent on fiber angle and sample aspect ratio, respectively, the objective of the present study was to evaluate the effects of a changing fiber angle and sample aspect ratio on the shear properties of aligned electrospun poly(epsilon-caprolactone) (PCL) scaffolds, and to determine how extracellular matrix deposition by resident MSCs modulates the measured shear response. Results show that fiber orientation and sample aspect ratio significantly influence the response of scaffolds in shear, and that measured shear strains can be predicted by finite element models. Furthermore, acellular PCL scaffolds possessed a relatively high shear modulus, 2-4 fold greater than native tissue, independent of fiber angle and aspect ratio. It was further noted that under testing conditions that engendered significant fiber stretch, the aggregate resistance to shear was higher, indicating a role for fiber stretch in the overall shear response. Finally, with time in culture, the shear modulus of MSC laden constructs increased, suggesting that deposited ECM contributes to the construct shear properties. Collectively, these findings show that aligned electrospun PCL scaffolds are a promising tool for engineering fibrocartilage tissues, and that the shear properties of both acellular and cell-seeded formulations can match or exceed native tissue benchmarks. PMID- 22098867 TI - Fibre-reinforced calcium phosphate cements: a review. AB - Calcium phosphate cements (CPC) consist of one or more calcium orthophosphate powders, which upon mixing with water or an aqueous solution, form a paste that is able to set and harden after being implanted within the body. Different issues remain still to be improved in CPC, such as their mechanical properties to more closely mimic those of natural bone, or their macroporosity to favour osteointegration of the artificial grafts. To this end, blends of CPC with polymer and ceramic fibres in different forms have been investigated. The present work aims at providing an overview of the different approaches taken and identifying the most significant achievements in the field of fibre-reinforced calcium phosphate cements for clinical applications, with special focus on their mechanical properties. PMID- 22098868 TI - In vivo evaluation of micro-rough and bioactive titanium dental implants using histometry and pull-out tests. AB - We report on the in vivo histological and mechanical performance of titanium dental implants with a new surface treatment (2Step) consisting of an initial grit-blasting process to produce a micro-rough surface, followed by a combined chemical and thermal treatment that produces a potentially bioactive surface, i.e., that can form an apatitic layer when exposed to biomimetic conditions in vitro. Our aim was to assess the short- and mid-term bone regenerative potential and mechanical retention of 2Step implants in mandible and maxilla of minipigs and compare them with micro-rough grit-blasted, micro-rough acid-etched, and smooth as-machined titanium implants. The percent of bone-to-implant contact after 2, 4, 6, and 10 weeks of implantation as well as the mechanical retention after 4, and 6 weeks of implantation were evaluated with histometric and pull-out tests, respectively, as a measure of the osseointegration of the implants. We also aimed to assess the bioactive nature of 2Step surfaces in vivo. Our results demonstrated that the 2Step treatment produced micro-rough and bioactive implants that accelerated bone tissue regeneration and increased mechanical retention in the bone bed at short periods of implantation in comparison with all other implants tested. This was mostly attributed to the ability of 2Step implants to form in vivo a layer of apatitic mineral that coated the implant and could rapidly stimulate (a) bone nucleation directly on the implant surface, and (b) bone growing from the implant surface. We also proved that roughness values of Ra~4.5 MUm favoured osseointegration of dental implants at short- and mid-term healing periods, as grit-blasted implants and 2Step implants had higher retention values than as machined and acid-etched implants. The surface quality resulting from the 2Step treatment applied on cpTi provided dental implants with a unique combination of rapid bone regeneration and high mechanical retention. PMID- 22098869 TI - A constrained mixture approach to mechano-sensing and force generation in contractile cells. AB - Biological tissues are very particular types of materials that have the ability to change their structure, properties and chemistry in response to external cues. Contractile cells, i.e. fibroblasts, are key players of tissue adaptivity as they are capable of reorganizing their surrounding extra-cellular matrix (ECM) by contracting and generating mechanical forces. This contractile behavior is attributed to the development of a stress-fiber (SF) network within the cell's cytoskeleton, a process that is known to be highly dependent of the nature of the mechanical environment (such as ECM stiffness or the presence of stress and strain). To describe these processes in a consistent manner, the present paper introduces a mutiphasic formulation (fluid/solid/solute mixture) that accounts for four major elements of cell contraction: cytoskeleton, cytosol, SF and actin monomers, as well as their interactions. The model represents the cross-talks between mechanics and chemistry through various means: (a) a mechano-sensitive formation and dissociation of an anisotropic SF network described by mass exchange between actin monomer and polymers, (b) a bio-mechanical model for SF contraction that captures the well-known length-tension and velocity-tension relation for muscles cells and (c) a convection/diffusion description for the transport of fluid and monomers within the cell. Numerical investigations show that the multiphasic model is able to capture the dependency of cell contraction on the stiffness of the mechanical environment and accurately describes the development of an oriented SF network observed in contracting fibroblasts. PMID- 22098870 TI - Bioactive composite for keratoprosthesis skirt. AB - In this study, the fabrication and properties of a synthetic keratoprosthesis skirt for use in osteo-odonto-keratoprosthesis (OOKP) surgery are discussed. In the search for a new material concept, bioactive glass and polymethyl methacrylate (PMMA)-based composites were prepared. Three different bioactive glasses (i.e. 45S5, S53P4 and 1-98) and one slowly resorbing glass, FL107, with two different forms (i.e. particles and porous glass structures) were employed in the fabrication of specimens. In in vitro studies, the dissolution behaviour in simulated aqueous humour, compressive properties, and pore formation of the composites were investigated. According to the results, FL107 dissolved very slowly (2.4% of the initial glass content in three weeks); thus, the pore formation of the FL107 composite was also observed to be restricted. The dissolution rates of the bioactive glass-PMMA composites were greater (12%-17%). These faster dissolving bioactive glass particles caused some porosity on the outermost surfaces of the composite. The slight surface porosity was also confirmed by a decrease in compressive properties. During six weeks' in vitro dissolution, the compressive strength of the test specimens containing particles decreased by 22% compared to values in dry conditions (90-107 MPa). These results indicate that the bioactive composites could be stable synthetic candidates for a keratoprosthesis skirt in the treatment of severely damaged or diseased cornea. PMID- 22098871 TI - Enhanced mechanical properties and in vitro corrosion behavior of amorphous and devitrified Ti40Zr10Cu38Pd12 metallic glass. AB - The effects of annealing treatments on the microstructure, elastic/mechanical properties, wear resistance and corrosion behavior of rod-shaped Ti40Zr10Cu38Pd12 bulk glassy alloys, synthesized by copper mold casting, are investigated. Formation of ultrafine crystals embedded in an amorphous matrix is observed for intermediate annealing temperatures, whereas a fully crystalline microstructure develops after heating to sufficiently high temperatures. The glassy alloy exhibits large hardness, relatively low Young's modulus, good wear resistance and excellent corrosion behavior. Nanoindentation measurements reveal that the sample annealed in the supercooled liquid region exhibits a hardness value of 9.4 GPa, which is 20% larger than in the completely amorphous state and much larger than the hardness of commercial Ti-6Al-4V alloy. The Young's modulus of the as-cast alloy (around 100 GPa, as determined from acoustic measurements) increases only slightly during partial devitrification. Finally, the anticorrosion performance of the Ti40Zr10Cu38Pd12 alloy in Hank's solution has been shown to ameliorate as crystallization proceeds and is roughly as good as in the commercial Ti-6Al-4V alloy. The outstanding mechanical and corrosion properties of the Ti40Zr10Cu38Pd12 alloy, both in amorphous and crystalline states, are appealing for its use in biomedical applications. PMID- 22098872 TI - Shear bond strength of a hot pressed Au-Pd-Pt alloy-porcelain dental composite. AB - OBJECTIVES: The purpose of this study was to evaluate the effect of hot pressing on the shear bond strength of a Au-Pt-Pd alloy-porcelain composite. METHODS: Several metal-porcelain composites specimens were produced by two different routes: conventional porcelain fused to metal (PFM) and hot pressing. In the latter case, porcelain was hot pressed onto a polished surface (PPPS) as well as a roughened one (PPRS). Bond strength of all metal-porcelain composites were assessed by the means of a shear test performed in a universal test machine (crosshead speed: 0.5 mm/min) until fracture. Interfaces of fractured specimens as well as undestroyed interface specimens were examined with optical microscope, stereomicroscope, Scanning Electron Microscope (SEM) and Energy Dispersive X-Ray Spectroscopy (EDS). The data were analyzed using one-way ANOVA followed by Tuckey's test (p<0.05). RESULTS: Shear bond strength of conventional PFM specimens were in line with the upper range of literature data (83+/-14 MPa). Hot pressing proved to significantly increase bond strength between metal and porcelain (p<0.05). For both polished and roughened surface the shear bond strength values for hot pressed specimens were 120+/-16 MPa and 129+/-5 MPa, respectively, which represents an improvement of more than 50% relatively to a conventional PFM. Roughened surface did not have a significant effect on bond strength of hot pressed specimens (p>0.05). SIGNIFICANCE: This study shows that it is possible to significantly improve metal-porcelain bond strength by applying an overpressure during porcelain firing. PMID- 22098873 TI - Biaxial mechanical modeling of the small intestine. AB - Capsule endoscopes are pill-size devices provided with a camera that capture images of the small intestine from inside the body after being ingested by a patient. The interaction between intestinal tissue and capsule endoscopes needs to be investigated to optimize capsule design while preventing tissue damage. To that purpose, a constitutive model that can reliably predict the mechanical response of the intestinal tissue under complex mechanical loading is required. This paper describes the development and numerical validation of a phenomenological constitutive model for the porcine duodenum, jejunum and ileum. Parameters characterizing the mechanical behavior of the material were estimated from planar biaxial test data, where intestinal tissue specimens were simultaneously loaded along the circumferential and longitudinal directions. Specimen-specific Fung constitutive models were able to accurately predict the planar stress-strain behavior of the tested samples under a wide range of loading conditions. To increase model generality, average anisotropic constitutive relationships were also generated for each tissue region by fitting average stress-strain curves to the Fung potential. Due to the observed variability in the direction of maximum stiffness, the average Fung models were less anisotropic than the specimen-specific models. Hence, average isotropic models in the Neo Hookean and Mooney-Rivlin forms were attempted, but they could not adequately describe the degree of nonlinearity in the tissue. Values of the R2 for the nonlinear regressions were 0.17, 0.44 and 0.93 for the average Neo-Hookean, Mooney-Rivlin and Fung models, respectively. Average models were successfully implemented into FORTRAN routines and used to simulate capsule deployment with a finite element method analysis. PMID- 22098874 TI - Phantom elasticity reconstruction with Digital Image Elasto-Tomography. AB - Results from the application of a novel nonlinear hybrid reconstruction algorithm within a Digital Image Elasto-Tomography (DIET) system are presented. A hybrid reconstruction algorithm was optimized to solve for the elasticity distribution of two heterogeneous silicone phantoms using a shape-based parameterization. The hybrid algorithm achieved comparable performance to Combinatorial Optimization methods with significantly less computational expense. The specificity of three parameter reconstruction was confirmed by successful reconstruction of a homogeneous silicone phantom, indicating the potential suitability of the DIET system for application to inclusion imaging in elastography. PMID- 22098875 TI - Study of the behavior of the trabecular bone under cyclic compression with stepwise increasing amplitude. AB - This paper presents the results of a study of 61 trabecular bone samples exposed to a cyclic (1 Hz) compression load. The load was increased stepwise. Characteristic patterns of the hysteresis loop for the middle cycles of successive steps of load and for respective steps of load are presented. Characteristic patterns of secant modulus were also determined. The fatigue life results recorded were compared with the indices of bone architecture determined using micro-CT. Using Pearson's correlation, the best relationship between fatigue life and bone volume ratio (BV/TV) and the maximum load for which there was also reported a maximal value secant stiffness were identified. Based on these findings, it was determined that it is possible to use stepwise increasing load for analysis of the fatigue behavior of trabecular bone. PMID- 22098876 TI - Fracture characterization of bone under mode II loading using the end loaded split test. AB - Fracture energy release rate under mode II loading of bovine cortical bone is determined using a miniaturized testing device of the end loaded split test. The energy release rate is evaluated by means of a data reduction scheme based on specimen compliance, beam theory and crack equivalent concept. Experimental tests were carried out to evaluate the Resistance curve which provides a successful method to characterize fracture behavior of quasi-brittle materials like bone. A numerical analysis including a cohesive damage model was used to validate the procedure. It was demonstrated that the end loaded split test and proposed data reduction scheme provide a valuable solution for mode II fracture characterization of bone. PMID- 22098877 TI - Effect of high-energy X-ray doses on bone elastic properties and residual strains. AB - Bone X-ray irradiation occurs during medical treatments, sterilization of allografts, space travel and in vitro studies. High doses are known to affect the post-yield properties of bone, but their effect on the bone elastic properties is unclear. The effect of such doses on the mineral-organic interface has also not been adequately addressed. Here, the evolution of elastic properties and residual strains with increasing synchrotron X-ray dose (5-3880 kGy) is examined on bovine cortical bone. It is found that these doses affect neither the degree of nanometer-level load transfer between the hydroxyapatite (HAP) platelets and the collagen up to stresses of -60 MPa nor the microscopic modulus of collagen fibrils (both measured by synchrotron X-ray scattering during repeated in situ loading and unloading). However, the residual elastic strains in the HAP phase decrease markedly with increased irradiation, indicating damage at the HAP collagen interface. The HAP residual strain also decreases after repeated loading/unloading cycles. These observations can be explained by temporary de bonding at the HAP/collagen interface (thus reducing the residual strain), followed by rapid re-bonding (so that load transfer capability is not affected). PMID- 22098878 TI - Similar damage initiation but different failure behavior in trabecular and cortical bone tissue. AB - The mechanical properties of bone tissue are reflected in its micro- and nanostructure as well as in its composition. Numerous studies have compared the elastic mechanical properties of cortical and trabecular bone tissue and concluded that cortical bone tissue is stiffer than trabecular bone tissue. This study compared the progression of microdamage leading to fracture and the related local strains during this process in trabecular and cortical bone tissue. Unmachined single bovine trabeculae and similarly-sized cortical bovine bone samples were mechanically tested in three-point bending and concomitantly imaged to assess local strains using a digital image correlation technique. The bone whitening effect was used to detect microdamage formation and propagation. This study found that cortical bone tissue exhibits significantly lower maximum strains (trabecular 36.6%+/-14% vs. cortical 22.9%+/-7.4%) and less accumulated damage (trabecular 16100+/-8800 pix/mm2 vs. cortical 8000+/-3400 pix/mm2) at failure. However, no difference was detected for the maximum local strain at whitening onset (trabecular 5.8%+/-2.6% vs. cortical 7.2%+/-3.1%). The differences in elastic modulus and mineral distribution in the two tissues were investigated, using nanoindentation and micro-Raman imaging, to explain the different mechanical properties found. While cortical bone was found to be overall stiffer and more highly mineralized, no apparent differences were noted in the distribution of modulus values or mineral density along the specimen diameter. Therefore, differences in the mechanical behavior of trabecular and cortical bone tissue are likely to be in large part due to microstructural (i.e. orientation and distribution of cement lines) and collagen related compositional differences. PMID- 22098879 TI - Interface shear strength and fracture behaviour of porous glass-fibre-reinforced composite implant and bone model material. AB - Glass-fibre-reinforced composites (FRCs) are under current investigation to serve as durable bone substitute materials in load-bearing orthopaedic implants and bone implants in the head and neck area. The present form of biocompatible FRCs consist of non-woven E-glass-fibre tissues impregnated with varying amounts of a non-resorbable photopolymerisable bifunctional polymer resin with equal portions of both bis-phenyl-A-glycidyl dimethacrylate (BisGMA) and triethyleneglycol dimethacrylate (TEGDMA). FRCs with a total porosity of 10-70 vol% were prepared, more than 90 vol% of which being functional (open pores), and the rest closed. The pore sizes were greater than 100 MUm. In the present study, the push-out test was chosen to analyse the shear strength of the interface between mechanically interlocked gypsum and a porous FRC implant structure. Gypsum was used as a substitute material for natural bone. The simulative in vitro experiments revealed a significant rise of push-out forces to the twofold level of 1147 +/- 271 N for an increase in total FRC porosity of 43%. Pins, intended to model the initial mechanical implant fixation, did not affect the measured shear strength of the gypsum-FRC interface, but led to slightly more cohesive fracture modes. Fractures always occurred inside the gypsum, it having lower compressive strength than the porous FRC structures. Therefore, the largest loads were restricted by the brittleness of the gypsum. Increases of the FRC implant porosity tended to lead to more cohesive fracture modes and higher interfacial fracture toughness. Statistical differences were confirmed using the Kruskal-Wallis test. The differences between the modelled configuration showing gypsum penetration into all open pores and the real clinical situation with gradual bone ingrowth has to be considered. PMID- 22098881 TI - Mechanical characterization and numerical simulation of polyether-ether-ketone (PEEK) cranial implants. AB - Cranial implants have experienced a significant evolution in the last decade in different aspects such as materials, method of fixation, and the structure. In addition, patient-specific cranial implants have recently been started to be developed. To achieve this objective, efficient mechanical characterization and numerical modeling of the implant are required to guarantee its functionality on each patient as well as to facilitate further developments. In this work, mechanical characterization and numerical models have been performed for patient specific Polyaryletherketone (PEEK) scaffold cranial implants. Mechanical characterization has been performed at the scaffold and the whole implant levels under displacement control tests. Two different implant designs for the same patient but with different scaffold structure were experimentally characterized, and finite element models of the implants were developed within the framework of linear elasticity. Two types of finite element models were developed: a detailed finite element model with the actual scaffold geometry, and a solid shell-like model with effective material properties. These effective material properties were obtained by means of the Asymptotic Expansion Homogenization (AEH) theory which accounts for the periodicity of the underlying structure of the material. Experimental results showed a linear response of the material and the implant up to failure, therefore supporting the use of linear elastic models for simulation. Numerical models showed excellent agreement with experiments regarding load displacement response. Models also showed a very consistent behavior with regard to the location and the value of the maximum principal stress in the implant when subjected to the maximum load of the experiments. The two numerical models were compared. The homogenized model gave results that were very close to those obtained with the detailed model, while reducing the number of degrees of freedom by 90%, and therefore the overall computational burden. The results showed that the models are able to reproduce experimental results conducted on actual implants, offering a valid alternative to be used in the design of customized cranial implants with a scaffold structure. PMID- 22098880 TI - Manipulation of mechanical compliance of elastomeric PGS by incorporation of halloysite nanotubes for soft tissue engineering applications. AB - Poly (glycerol sebacate) (PGS) is a promising elastomer for use in soft tissue engineering. However, it is difficult to achieve with PGS a satisfactory balance of mechanical compliance and degradation rate that meet the requirements of soft tissue engineering. In this work, we have synthesised a new PGS nanocomposite system filled with halloysite nanotubes, and mechanical properties, as well as related chemical characters, of the nanocomposites were investigated. It was found that the addition of nanotubular halloysite did not compromise the extensibility of material, compared with the pure PGS counterpart; instead the elongation at rupture was increased from 110 (in the pure PGS) to 225% (in the 20 wt% composite). Second, Young's modulus and resilience of 3-5 wt% composites were ~0.8 MPa and >94% respectively, remaining close to the level of pure PGS which is desired for applications in soft tissue engineering. Third, an important feature of the 1-5 wt% composites was their stable mechanical properties over an extended period, which could allow the provision of reliable mechanical support to damaged tissues during the lag phase of the healing process. Finally, the in vitro study indicated that the addition of halloysite slowed down the degradation rate of the composites. In conclusion, the good compliance, enhanced stretchability, stable mechanical behavior over an extended period, and reduced degradation rates make the 3-5 wt% composites promising candidates for application in soft tissue engineering. PMID- 22098882 TI - Equivalent mechanical properties of biological membranes from lattice homogenization. AB - The goal of this manuscript is to set up a novel methodology for the calculation of the effective mechanical properties of biological membranes viewed as repetitive networks of elastic filaments, based on the discrete asymptotic homogenization method. We will show that for some lattice configurations, flexional effects due to internal structure mechanisms at the unit cell scale lead to additional flexional effects at the continuum scale, accounted for by an internal length associated to a micropolar behavior. Thereby, a systematic methodology is established, allowing the prediction of the overall mechanical properties of biological membranes for a given network topology, as closed form expressions of the geometrical and mechanical micro-parameters. The peptidoglycan and the erythrocyte have been analyzed using this methodology, and their effective moduli are calculated and recorded versus the geometrical and mechanical lattice parameters. A classification of lattices with respect to the choice of the equivalent continuum model is proposed: The Cauchy continuum and a micropolar continuum are adopted as two possible effective medium, for a given beam model. The relative ratio of the characteristic length of the micropolar continuum to the unit cell size determines the relevant choice of the equivalent medium. In most cases, the Cauchy continuum is sufficient to model membranes in most of their configurations. The peptidoglycan network may exhibit a re-entrant hexagonal lattice, for which micropolar effects become important. This is attested by the characteristic length becoming larger than the beam length for such configurations. The homogenized moduli give accurate results for both membranes, as revealed by comparison with experimental measurements or simulation results from the literature at the network scale. A first insight into the nonlinear mechanical behavior of the hexagonal and triangular networks is lastly investigated using a perturbative method. PMID- 22098883 TI - Influence of molecular weight of polymethyl(methacrylate) beads on the properties and structure of cross-linked denture base polymer. AB - OBJECTIVES: Denture base polymers are multiphase polymers made of polymethyl(methacrylate) (PMMA) beads and monomers containing methylmethacrylate and cross-linking agent. The cross-linking agent is typically dimethacrylate but methacrylated dendrimers have been tested. The aim of this study was to investigate the influence of the molecular weight of the PMMA beads on the mechanical properties of cross-linked denture base polymers. METHODS: Resin powder with three different molecular weights (Mw 120,000, 350,000, and 996,000) and a commercial autopolymerizing denture base resin (Palapress, Mw 220,000) were tested. The resin monomer liquid was applied with a methylmethacrylate mixture containing 4.6 vol% dendrimer (DD1, VTT Processes). To investigate the flexural properties, the surface microhardness of the PMMA beads, and the thickness of the swollen interpenetrating polymer network (IPN) layer on the PMMA beads, test specimens (3.3*10*65 mm) were fabricated from autopolymerizing resin using a powder/liquid ratio of 10 g/7 ml. The specimens were polymerized in distilled water maintained at 55 degrees C under 0.4 MPa pressure for 20 min. The flexural strength and flexural modulus (n=8/group) were measured with a three-point bending test at a crosshead speed of 5 mm/min. The Vickers hardness of the area of the polymer with PMMA beads (n=10/group) was tested using a load of 98.12 mN for 5 s. In addition, the thickness of the swollen layer on the PMMA beads was measured (n=10/group). Statistical analysis was performed using a one-way ANOVA and Tukey's test. RESULTS: The flexural strength of the specimens with Mw 220,000 and 350,000 PMMA beads was significantly higher than the strength of specimens with beads having other molecular weights. The flexural modulus of specimens with Mw 120,000 PMMA beads was the lowest. There was no difference in the surface microhardness among all groups. The thickness of the swollen IPN layer on specimens with 120,000 Mw PMMA beads was significantly higher than in the other groups. CONCLUSIONS: The molecular weight of the PMMA beads of multiphase denture base polymers considerably influences their flexural properties and formation of IPN layer between the matrix polymer and the PMMA beads. PMID- 22098884 TI - Role of damage mechanics in nanoindentation of lamellar bone at multiple sizes: experiments and numerical modeling. AB - The aim of this paper is to show that damage mechanisms can account for the response of lamellar bone to nanoindentation tests, with particular regards to the decrease of indentation stiffness with increasing penetration depth and to the loss of contact stiffness during the unloading phase of the test. For this purpose, indentation experiments on bovine cortical bone samples along axial and transverse directions have been carried out at five penetration depths from 50 to 450 nm; furthermore, a continuum damage model has been implemented into finite element analyses, which are able to simulate indentation experiments. Experiments along the axial direction have shown a decrease of about 20% of the indentation modulus with indentation depth; a similar trend was found along the transverse direction. All unloading branches of the force-displacement indentation curves exhibited relevant stiffness loss (curve concavity). The numerical model with damage was able to correctly predict the indentation stiffness and hardness at 300 nm penetration depth along both axial and transverse directions. Furthermore, stiffness loss during unloading was simulated with both qualitative and quantitative agreement with experiments. A final validation has been provided by simulating axial indentation experiments at the remaining penetration depths using the same set of constitutive parameters as those used to simulate the experiments at 300 nm depth. These results support the hypothesis that damage plays a relevant role in the mechanics of lamellar bone and should be taken into account when studying bone mechanical properties at multiple scales. PMID- 22098885 TI - A thermo-mechanical treatment to improve the superelastic performances of biomedical Ti-26Nb and Ti-20Nb-6Zr (at.%) alloys. AB - A flash-thermal treatment technique has been developed very recently to improve both the critical stress to induce the martensitic transformation (MT) and the recoverable deformation of the metastable beta type titanium alloys. In this paper, this strategy is applied to both Ti-26Nb and Ti-20Nb-6Zr (at.%) alloys. Since both alloys have identical martensite start (Ms) temperature, it makes possible to investigate the effect of Zr on mechanical properties after the flash thermal treatment. It is clearly shown that a flash treatment of 360 s at 873 K on heavily cold-rolled samples results in good balance between the tensile strength, the ductility and the recoverable strains. Such contribution is more significant in the ternary alloy in which balanced properties combining high martensitic critical stress over 400 MPa and the large fully recoverable strains up to 3.0% can be achieved. These improvements are due to the flash treatment effects, resulting in ultra-fine beta grains with sizes 1-2 MUm with nano-sized alpha and omega phases precipitation in the beta matrix. PMID- 22098886 TI - Wear resistance of experimental titanium alloys for dental applications. AB - The present study evaluated microstructure, microhardness and wear resistance of experimental titanium alloys containing zirconium and tantalum. Alloys were melted in arc melting furnace according to the following compositions: Ti-5Zr, Ti 5Ta and Ti-5Ta-5Zr (%wt). Hemispheres and disks were obtained from wax patterns that were invested and cast by plasma. Microstructures were evaluated using optical microscopy and X-ray diffraction (XRD) analysis and also Vickers microhardness was measured. Hemispherical samples and disks were used for 2-body wear tests, performed by repeated grinding of the samples. Wear resistance was assessed as height loss after 40,000 cycles. The data were compared using ANOVA and post-hoc Tukey test. Ti-5Zr presented a Widmanstatten structure and the identified phases were alpha and alpha' while Ti-5Ta and Ti-5Ta-5Zr presented alpha, beta, alpha' and alpha" phases, but the former presented a lamellar structure, and the other, acicular. The microhardness of Ti-5Zr was significantly greater than other materials and cp Ti presented wear resistance significantly lower than experimental alloys. It was concluded that wear resistance was improved when adding Ta and Zr to titanium and Zr increased microhardness of Ti 5Zr alloy. PMID- 22098887 TI - Computer simulating a clinical trial of a load-bearing implant: an example of an intramedullary prosthesis. AB - Computational modelling is becoming ever more important for obtaining regulatory approval for new medical devices. An accepted approach is to infer performance in a population from an analysis conducted for an idealised or 'average' patient; we present here a method for predicting the performance of an orthopaedic implant when released into a population--effectively simulating a clinical trial. Specifically we hypothesise that an analysis based on a method for predicting the performance in a population will lead to different conclusions than an analysis based on an idealised or 'average' patient. To test this hypothesis we use a finite element model of an intramedullary implant in a bone whose size and remodelling activity is different for each individual in the population. We compare the performance of a low Young's modulus implant (E=20 GPa) to one with a higher Young's modulus (200 GPa). Cyclic loading is applied and failure is assumed when the migration of the implant relative to the bone exceeds a threshold magnitude. The analysis for an idealised of 'average' patient predicts that the lower modulus device survives longer whereas the analysis simulating a clinical trial predicts no statistically-significant tendency (p=0.77) for the low modulus device to perform better. It is concluded that population-based simulations of implant performance-simulating a clinical trial-present a very valuable opportunity for more realistic computational pre-clinical testing of medical devices. PMID- 22098888 TI - Surface integrity of biodegradable Magnesium-Calcium orthopedic implant by burnishing. AB - Magnesium-Calcium (MgCa) alloy as an emerging biodegradable implant material has received considerable attention in orthopedic fixation applications. The biodegradable MgCa alloys avoid stress shielding and secondary surgery inherent with permanent metallic implant materials. They also provide sufficient mechanical strength in load carrying applications as opposed to biopolymers. However, the key issue facing a biodegradable MgCa implant is the fast corrosion in the human body environment. The ability to adjust the degradation rate of MgCa alloys is critical in the successful development of biodegradable orthopedic materials. Burnishing as a low plastic deformation process is a promising technique to tune surface integrity of MgCa implant surface for biodegradation control. However, the poor ductility of MgCa alloys imposes a great challenge for burnishing. This study focuses on the basic understanding of surface mechanical behavior of burnished biodegradable MgCa0.8 (wt%) alloy. The effects of burnishing parameters, i.e., pressure, feed, speed, number of path, and burnishing pattern on surface integrity factors such as surface topography, roughness, microhardness, microstructure, and residual stresses are investigated. The burnished surfaces are shinier and smoother than the as-machined ones. The MgCa alloy can be safely burnished at suitable burnishing conditions since no cracks are produced at the surface and in the subsurface. The microstructure including grain size does not show a noticeable change after burnishing. The machined surfaces are harder than the burnished ones down to the deep subsurface (~200 MUm) as opposed to the shallow hardened depth (~50 MUm) in cutting. Residual stresses are highly compressive especially at low burnishing pressure. PMID- 22098889 TI - Computation of axonal elongation in head trauma finite element simulation. AB - In the case of head trauma, elongation of axons is thought to result in brain damage and to lead to Diffuse Axonal Injuries (DAI). Mechanical parameters have been previously proposed as DAI metric. Typically, brain injury parameters are expressed in terms of pressure, shearing stresses or invariants of the strain tensor. Addressing axonal deformation within the brain during head impact can improve our understanding of DAI mechanisms. A new technique based on directional measurements of water diffusion in soft tissue using Magnetic Resonance Imaging (MRI), called Diffusion Tensor Imaging (DTI), provides information on axonal orientation within the brain. The present study aims at coupling axonal orientation from a 12-patient-based DTI 3D picture, called "DTI atlas", with the Strasbourg University Finite Element Head Model (SUFEHM). This information is then integrated in head trauma simulation by computing axonal elongation for each finite element of the brain model in a post-processing of classical simulation results. Axonal elongation was selected as computation endpoint for its strong potential as a parameter for DAI prediction and location. After detailing the coupling technique between DTI atlas and the head FE model, two head trauma cases presenting different DAI injury levels are reconstructed and analyzed with the developed methodology as an illustration of axonal elongation computation. Results show that anisotropic brain structures can be realistically implemented into an existing finite element model of the brain. The feasibility of integrating axon fiber direction information within a dedicated post-processor is also established in the context of the computation of axonal elongation. The accuracy obtained when estimating level and location of the computed axonal elongation indicates that coupling classical isotropic finite element simulation with axonal structural anisotropy is an efficient strategy. Using this method, tensile elongation of the axons can be directly invoked as a mechanism for Diffuse Axonal Injury. PMID- 22098890 TI - Verification and implementation of a modified split Hopkinson pressure bar technique for characterizing biological tissue and soft biosimulant materials under dynamic shear loading. AB - Modeling human body response to dynamic loading events and developing biofidelic human surrogate systems require accurate material properties over a range of loading rates for various human organ tissues. This work describes a technique for measuring the shear properties of soft biomaterials at high rates of strain (100-1000 s(-1)) using a modified split Hopkinson pressure bar (SHPB). Establishing a uniform state of stress in the sample is a fundamental requirement for this type of high-rate testing. Input pulse shaping was utilized to tailor and control the ramping of the incident loading pulse such that a uniform stress state could be maintained within the specimen from the start of the test. Direct experimental verification of the stress uniformity in the sample was obtained via comparison of the force measured by piezoelectric quartz force gages on both the input and the output sides of the shear specimen. The technique was demonstrated for shear loading of silicone gel biosimulant materials and porcine brain tissue. Finite element simulations were utilized to further investigate the effect of pulse shaping on the loading rate and rise time. Simulations also provided a means for visualization of the degree of shear stress and strain uniformity in the specimen during an experiment. The presented technique can be applied to verify stress uniformity and ensure high quality data when measuring the dynamic shear modulus of soft biological simulants and tissue. PMID- 22098891 TI - Short-term fatigue testing can predict medium-term pericardium behaviour. AB - The medium-term fatigue behaviour of calf pericardium (similar to the one used to manufacture cardiac bioprostheses valve leaflets) has been studied. 96 samples were tested under fatigue subjecting them to biaxial stress at 1 Hz frequency for 5000 cycles, in 4 series of 24 samples, at several supra-physiological mean pressures and pressure amplitudes. Short-term damage parameters such as the accumulated energy consumption in 10 cycles (E10) and medium-term ones after 5000 cycles like total energy consumption (Et) and maximum displacement of the membrane (Dt) have been evaluated. E10 showed exponential growing tendency with pressure and linear tendency with pressure amplitude when only one parameter curve was plotted. Similar results were found when analysing Et and Dt. Linear correlation models were established between E10 and Et and E10 and Dt. Similar results were achieved in the four series, with excellent determination coefficients. The results confirm that the fatigue behaviour from the very first cycles of the test can predict the medium-term behaviour of the tissue by means of measurement of suitable damage markers. The tendencies observed between the parameters seem to show that the results could have been the same ones if the test had been performed at physiological pressures and amplitudes. This work opens the door to a non-destructive test of the tissue prior to employ it to manufacture valve leaflets. PMID- 22098892 TI - Mobile or fixed unicompartmental knee prostheses? In-vitro wear assessments to solve this dilemma. AB - The unicompartmental knee prosthesis is an attractive alternative to total knee arthroplasty. Current UKP devices can be subdivided into two groups based on different design principles: fixed bearing knees, where the ultra-high molecular weight polyethylene meniscal component snap or press fits into the tibial tray, and mobile bearing designs which facilitate movement of the insert relative to the tray. The present study was aimed at comparing the in-vitro wear behaviour of fixed and mobile unicompartmental knee menisci under two configurations: the femoral components were cemented into a custom-made metallic block or, as a novelty of the present study, into a synthetic femur (i.e. under conditions which should better reproduce the in-vivo behaviour). Analyses were performed using a displacement-control knee wear simulator with "three-plus-one" stations. All the kinematics tests were set in accordance with the ISO 14243-1,2,3. Fixed and mobile polyethylene menisci showed a different wear behaviour: the fixation-frame influenced directional load transfer through each component in a qualitative and quantitative way. In fact, gravimetric results showed that under the metal block holder fixation, mobile components worn more than fixed components (weight losses of 8.7+/-2.0 mg and 2.6+/-1.09 mg, respectively); on the other hand, under the synthetic femur configuration, differences in wear behaviour were less pronounced and mobile menisci underwent a slightly lower weight loss than fixed components (4.5+/-2.2 mg vs. 6.7+/-1.4 mg). This different trend was explained in relation to the kinematic schemes of the two fixation methods. Raman spectroscopy, used to evaluate the UHMWPE crystallinity changes induced by mechanical stress, showed that mobile menisci specimens were more affected than the fixed components in both their superior and inferior surfaces, independent of the fixation-frame. In conclusion, if tested under conditions which should better reproduce the in-vivo behaviour, mobile UKPs did not show a worse wear behaviour than fixed components in terms of weight losses, although UHMWPE changes at the molecular scale could be detrimental. PMID- 22098893 TI - A tri-phasic mixture model of bone resorption: theoretical investigations. AB - In this paper, for the first time, a tri-phasic model of bone resorption using a mixture with chemical reactions is proposed. Three constituents (matrix, fluid, and cells) are considered. Conservation equations and entropy inequality are provided. The dependent variables in the constitutive equations, such as the rate of resorption, are assumed to be a function of temperature, deformation gradient, and the extent of the chemical reactions. Using constitutive equations in the second law of thermodynamics, a criterion for the thermodynamic equilibrium state is obtained which contains a bio-chemo-mechanical affinity. Using the proposed model, one can find a theoretical explanation for some clinically observed behavior of bone, for instance for the greater rate of bone resorption in cortical than cancellous bone, using the conservation equations and/or consistency requirements of continuum mixture theory. This work can be seen as a first step towards establishing a new theoretical framework which could be developed in the future by collaborative work, and with the hope of shedding some light on the multidisciplinary and complex process of bone resorption. PMID- 22098894 TI - The effect of microstructure on fatigue performance of Ti-6Al-4V alloy after EDM surface treatment for application in orthopaedics. AB - Three different microstructures--equiaxed, bi-modal and coarse lamellar--are prepared from Ti-6Al-4V alloy. Electric discharge machining (EDM) with a high peak current (29 A) is performed in order to impose surface roughness and modify the chemical composition of the surface. Detailed scanning electron microscopy (SEM) investigation revealed a martensitic surface layer and subsurface heat affected zone (HAZ). EDX measurements showed carbon enriched remnants of the EDM process on the material surface. Rotating bending fatigue tests are undertaken for EDM processed samples for all three microstructures and also for electropolished-benchmark-samples. The fatigue performance is found to be rather poor and not particularly dependent on microstructure. The bi-modal microstructure shows a slightly superior high cycle fatigue performance. This performance can be further improved by a suitable heat treatment to an endurance limit of 200 MPa. PMID- 22098895 TI - Investigating a novel nanostructured fibrin-agarose biomaterial for human cornea tissue engineering: rheological properties. AB - In this work, the rheological properties of the biomaterial fibrin with different agarose concentrations, used for the generation of a bioengineered human corneal stroma by tissue engineering, before and after using a nanostructuring technique, were analyzed. The transparency of these artificial human stromas was also investigated. The temporal evaluation of the properties of these biomaterials is essential for the design of functional biological human corneal replacements. The nanostructuring technique used for the generation of nanostructured corneal constructs (NCCs) had a major influence on the rheological properties of the fibrin-agarose corneal equivalents. For an oscillatory shear stress of 1 Hz, well in the order of the natural oscillations of the human cornea, the NCCs had viscoelasticity values higher than those of non-nanostructured corneal constructs (N-NCCs), but similar to those of an ex vivo native cornea. The model that most resembled the rheological behavior of the native cornea was a fibrin-0.1% agarose concentration nanostructured construct. In addition, this artificial cornea model displayed optimal levels of transparency, similar to the native tissue. All these properties indicate that the fibrin-0.1% agarose concentration nanostructured construct might serve as an adequate candidate for the generation of an artificial complete cornea, not only for transplanting use but also for conducting pharmaceutical testing and biomedical research. PMID- 22098896 TI - The effect of different implant macrogeometries and surface treatment in early biomechanical fixation: an experimental study in dogs. AB - Implant surface characterization and biomechanical testing were made to evaluate the effect of different surface treatments along with different implant bulk configurations expressed as biomechanical fixation at early implantation times. Three implant surfaces, namely bioactive ceramic electrodeposition (ED), alumina blasted/acid etched (AB/AE), and resorbable blasting media (RBM) were fabricated in three implant macrogeometries (cylindrical, small chamber, and large chamber). All combinations between surface and bulk configurations were placed in the radii of beagle dogs (n=18), which were euthanized 14 and 40 days after surgery (n=9 animals per time in vivo). The implants were subjected to torque to interface fracture. Effects of time, surface, and macrogeometry on torque to interface fracture were evaluated by a GLM at 95% level of significance. The results showed a significant increase in torque as time elapsed in vivo (p<0.001), and that the ED surface presented significantly higher values compared to AB/AE and RBM (p<0.001) at both times. The small chamber only presented a significantly higher biomechanical fixation compared to other geometries at 40 days in vivo (p=0.02). Biomechanical fixation at 14 and 40 days was affected by implant surface treatment, whereas implant design only affected results at 40 days in vivo. PMID- 22098897 TI - Influences of ionic concentration on nanomechanical behaviors for remineralized enamel. AB - This study evaluates the influences of 8DSS peptide and ionic concentrations of simulated body fluid on remineralization behaviors. The polished enamel specimens were acid-demineralized, exposed briefly to 8DSS peptide solution, and then immersed into simulated body fluid (SBF) that favors mineral deposition. At various stages of treatment, nanohardness and elastic modulus were determined by nanoindentation. The results show that the nanomechanical properties of the acid demineralized enamel were greatly improved as increasing the ionic concentrations of SBF due to the acceleration of mineral deposition. Additionally, the demineralized enamel, treated with 8DSS peptide and immersed into SBF*2 solution, possesses the highest values of nanohardness and elastic modulus resulting from the combinative effects of surface roughness, morphology, microstructure and crystallinity of the newly formed nanocomposite of calcium phosphate carbonate and hydroxyapatite. The formation of pores in the subsurface induced a reduction in the nanomechanical properties for the enamel subjected into SBF*3 solution. PMID- 22098898 TI - Life expectancy of modular Ti6Al4V hip implants: influence of stress and environment. AB - Stress dependent electrochemical dissolution is identified as one of the key mechanisms governing surface degradation in fretting and crevice corrosion of biomedical implants. The present study focuses on delineating the roles of mechanical stress and chemical conditions on the life expectancy of modular hip implants. First, material removal on a stressed surface of Ti6Al4V subjected to single asperity contact is investigated experimentally to identify the influence of contact load, in-plane stress and chemical environment on mean wear rates. A range of known stress levels are applied to the specimen while its surface is mechanically stimulated in different non-reactive to oxidizing aqueous environments. Evolution of surface degradation is monitored, and its mechanism is elucidated. This phase allows estimation of Preston Constant which is later used in the analysis. Second phase of the work is semi-analytical and computational, where, based on the estimated Preston constant and other material and process parameters, the scratch propensity (consisting of magnitude of scratch depth and their frequency per unit area) due to micro-motion in modular hip implants is estimated. The third phase views these scratches as initial notches and utilizes a mixed-mode fatigue crack propagation model to estimate the critical crack length for onset of instability. The number of loading cycles needed to reach this critical crack length is then labeled as the expected life of the implant under given mechanical and chemical conditions. Implications of different material and process conditions to life expectancy of orthopedic implants are discussed. It is observed that transverse micro-motion, compared to longitudinal micro-motion, plays a far more critical role in determining the implant life. Patient body weight, as well as proximity of the joint fluid to its iso-electric point play key roles in determining wear rates and associated life expectancies of modular hip implants. Sustained aeration of joint fluid, as well as proper tolerancing of mating surfaces, along with a proper choice of material microstructure may be utilized to extend implant life. PMID- 22098899 TI - Failure of silicone gel breast implants: is the mechanical weakening due to shell swelling a significant cause of prostheses rupture? AB - Silicone gel-filled breast implants nowadays are commonly used in breast surgery. Despite the improvements carried out during the years in the device design and manufacturing technologies, the long-term reliability of such prostheses is still doubted and the phenomena involved in the prostheses failure not yet clearly defined. This study investigates rupture causes by analysing the mechanical properties of failed and intact implants in the recent generation of silicon gel breast implants. The main scope is to assess whether mechanical weakness of the shells should be considered as a major cause of breast implant rupture or, on the contrary, the prosthesis shell damage is likely due to other random factors. Some tests were performed on the shells of a wide number of explanted prostheses, to evaluate the mechanical properties as a function of prostheses status at explantation (intact/ruptured) and variable degree of swelling. A weakening of the shell mechanical properties, so as a significant difference in the ultimate strength and stiffness of intact versus ruptured prostheses, was found. This attenuation of the properties may be justified as a consequence of the shell swelling phenomenon during implantation and has to be considered as a significant mechanism for silicone gel breast implant failure. PMID- 22098900 TI - Relationship between various deformation-induced products and mechanical properties in metastable Ti-30Zr-Mo alloys for biomedical applications. AB - Nowadays, there is a significant research focus on the development of bio-implant materials that have not only a low Young's modulus but also other unique characteristics such as a changeable Young's modulus and the ability to prevent calcium phosphate formation. Taking advantage of deformation-induced phases is an effective way to obtain the changeable Young's modulus. This study investigated the relationship between the various deformation-induced products and the mechanical properties-including Young's modulus, microstructure, and tensile properties-of Ti-30Zr-(5,6,7)mass%Mo alloys subjected to solution treatment (ST) and cold-rolling (CR). After ST, each alloy is composed of a beta phase and a small amount of athermally formed omega phase, and exhibits a low Young's modulus. During CR, deformation-induced phase transformation occurs in all the alloys. The change in Young's modulus due to CR is highly dependent on the types of deformation-induced products. The decrease in Young's modulus due to CR is related to the deformation-induced alpha' phase transformation accompanying with the disappearance of athermal omega phase, and the increase in Young's modulus is attributed to the deformation-induced omega phase, which mainly exists in {332}beta mechanical twins. PMID- 22098901 TI - Fatigue behavior of TiNi foams processed by the magnesium space holder technique. AB - While the wide range of applications of TiNi alloys makes them highly appealing due to their shape memory and superelasticity properties, the production of TiNi in the porous form further enlarges their application fields. Porous TiNi alloys have been studied extensively for biomedical applications since their elastic modulus is similar to that of bone. Accordingly, TiNi foams have been widely characterized in terms of their various mechanical properties; however, their fatigue properties have not been well studied, even though this is of vital importance in structural applications such as medical implants. In the scope of this study, TiNi foams processed from prealloyed powders by the magnesium space holder technique were mechanically characterized by monotonic and cyclic compression tests. TiNi foams with a porosity range of 49-64 vol.%, which is suitable for bone ingrowth, were determined to have a compressive strength varying in the range 93.27-273.45 MPa. Moreover, the wide range of elastic modulus values obtained (2.93-8.71 GPa) is promising for fulfilling various requirements of different implant applications without causing stress shielding. On the other hand, the endurance limit of TiNi foams was determined to be 0.6sigmay, where sigmay is the yield strength, independent of the porosity content. Fractography studies on the failed foams after fatigue testing revealed that the failure occurs by the coalescence of micro-cracks initiated from pore walls leading to macro-crack formation aligned at 45 degrees with respect to the loading axis. PMID- 22098902 TI - Regional and fiber orientation dependent shear properties and anisotropy of bovine meniscus. AB - Imaging of meniscal tissue reveals an extracellular matrix comprised of collagen fibrils arranged in circumferential bundles and radially aligned tie fibers, implicating structural material anisotropy. Biochemical analyses demonstrate regional disparities of proteoglycan content throughout the meniscal body, a constituent known to affect the shearing response of fibrocartilagenous tissue. Despite this phenomenological evidence and previous mechanical testing implicating otherwise, the meniscus if often modeled as a homogeneous, transversely isotropic material with little regard for regional specificity and material properties. The aim of this investigation was to determine if shear stress response homogeneity and directionality exists in and between bovine menisci with respect to anatomical location (medial and lateral), region (anterior, central, and posterior) and fiber orientation (parallel and perpendicular). Meniscus explants were subjected to lap shear strain at 0.002 s( 1) with the circumferential collagen fibers oriented parallel or perpendicular to the loading axis. Comparisons were made using a piecewise linear elastic analysis. The toe region shear modulus was calculated from the first observed linear region, between 3% and 13% strain and the extended shear modulus was established after 80% of the maximum shear strain. The posterior region was significantly different than the central for the extended shear modulus, correlating with known proteoglycan distribution. Observed shearing anisotropy led to the use of an anisotropic hyperelastic model based on a two-fiber family composite, previously used for arterial walls. The chosen model provided an excellent fit to the sample population for each region. These data can be utilized in the advancement of finite element modeling as well as biomimetic tissue engineered constructs. PMID- 22098903 TI - Biomechanics of the stick insect antenna: damping properties and structural correlates of the cuticle. AB - The antenna of the Indian stick insect Carausius morosus is a highly specialized near-range sensory probe used to actively sample tactile cues about location, distance or shape of external objects in real time. The length of the antenna's flagellum is 100 times the diameter at the base, making it a very delicate and slender structure. Like the rest of the insect body, it is covered by a protective exoskeletal cuticle, making it stiff enough to allow controlled, active, exploratory movements and hard enough to resist damage and wear. At the same time, it is highly flexible in response to contact forces, and returns rapidly to its straight posture without oscillations upon release of contact force. Which mechanical adaptations allow stick insects to unfold the remarkable combination of maintaining a sufficiently invariant shape between contacts and being sufficiently compliant during contact? What role does the cuticle play? Our results show that, based on morphological differences, the flagellum can be divided into three zones, consisting of a tapered cone of stiff exocuticle lined by an inner wedge of compliant endocuticle. This inner wedge is thick at the antenna's base and thin at its distal half. The decay time constant after deflection, a measure that indicates strength of damping, is much longer at the base (tau>25 ms) than in the distal half (tau<18 ms) of the flagellum. Upon experimental desiccation, reducing mass and compliance of the endocuticle, the flagellum becomes under-damped. Analysing the frequency components indicates that the flagellum can be abstracted with the model of a double pendulum with springs and dampers in both joints. We conclude that in the stick-insect antenna the cuticle properties described are structural correlates of damping, allowing for a straight posture in the instant of a new contact event, combined with a maximum of flexibility. PMID- 22098904 TI - Neutron diffraction residual strain measurements in nanostructured hydroxyapatite coatings for orthopaedic implants. AB - The failure of an orthopaedic implant can be initiated by residual strain inherent to the hydroxyapatite coating (HAC). Knowledge of the through-thickness residual strain profile in the thermally sprayed hydroxyapatite coating/substrate system is therefore important in the development of a new generation of orthopaedic implants. As the coating microstructure is complex, non-destructive characterization of residual strain, e.g. using neutron diffraction, provides a useful measure of through thickness strain profile without altering the stress field. This first detailed study using a neutron diffraction technique, non destructively evaluates the through thickness strain measurement in nanostructured hydroxyapatite plasma sprayed coatings on a titanium alloy substrate (as-sprayed, heat treated, and heat treated then soaked in simulated body fluid (SBF)). The influence of crystallographic plane orientation on the residual strain measurement is shown to indicate texturing in the coating. This texturing is expected to influence both the biological and fracture response of HA coatings. Results are discussed in terms of the influence of heat-treatment and SBF on the residual stress profile for these biomedical coatings. The results show that the through thickness residual strain in all three coatings was different for different crystallographic planes but was on average tensile. It is also concluded that the heat-treatment and simulated body fluid exposure had a significant effect on the residual strain profile in the top layers of HAC. PMID- 22098905 TI - Direct comparison of nanoindentation and macroscopic measurements of bone viscoelasticity. AB - Nanoindentation has become a standard method for measuring mechanical properties of bone, especially within microstructural units such as individual osteons or trabeculae. The use of nanoindentation to measure elastic properties has been thoroughly studied and validated. However, it is also possible to assess time dependent properties of bone by nanoindentation. The goal of this study was to compare time dependent mechanical properties of bone measured at the macroscopic level with those measured by nanoindentation. Twelve samples were prepared from the posterior distal femoral cortex of young cows. Initially, dogbone samples were prepared and subjected to torsional stress relaxation in a saline bath at 37 degrees C. A 5 mm thick disk was subsequently sectioned from the gage length, and subjected to nanoindentation. Nanoindentation was performed on hydrated samples using a standard protocol with 20 indents performed in 20 different osteons in each sample. Creep and stress relaxation data were fit to a Burgers four parameter rheological model, a five parameter generalized Maxwell model, and a three parameter standard linear solid. For Burgers viscoelastic model, the time constants measured by nanoindentation and torsion were weakly negatively correlated, while for the other two models the time constants were uncorrelated. The results support the notion that the viscoelastic behavior of bone at the macroscopic scale is primarily due to microstructural features, interfaces, or fluid flow, rather than viscous behavior of the bone tissue. As viscoelasticity affects the fatigue behavior of materials, the microscale properties may provide a measure of bone quality associated with initial damage formation. PMID- 22098906 TI - Mechanical parameters of strontium doped hydroxyapatite sintered using microwave and conventional methods. AB - The effects of ion substitution in hydroxyapatite (HA) on crystal structure and lattice stability is investigated in the green state and post sintering. The effects of ion incorporation on the biaxial flexural strength and hardness are also investigated. Sintering is carried out at 1200 degrees C using comparative conventional and microwave regimes. Post sintering, the effects of ion incorporation manifest as an increase in the lattice d-spacings and a reduction of the crystallite size. Some HA decomposition occurs with beta-TCP stabilisation in conventional sintering (CS), but this phase is destabilised during microwave sintering (MS), generating alpha-TCP. Conventional sintering (CS) allows higher densification in the undoped samples. Overall, for the Sr-doped compositions, the MS samples retain higher amounts of HA and experience higher density levels compared to the CS samples. PMID- 22098908 TI - Bone marrow modified acrylic bone cement for augmentation of osteoporotic cancellous bone. AB - The use of polymethylmethacrylate (PMMA) cement to reinforce fragile or broken vertebral bodies (vertebroplasty) leads to extensive bone stiffening. This might be one reason for fractures at the adjacent vertebrae following this procedure. PMMA with a reduced Young's modulus may be more suitable. The goal of this study was to produce and characterize PMMA bone cements with a reduced Young's modulus by adding bone marrow. Bone cements were produced by combining PMMA with various volume fractions of freshly harvested bone marrow from sheep. Porosity, Young's modulus, yield strength, polymerization temperature, setting time and cement viscosity of different cement modifications were investigated. The samples generated comprised pores with diameters in the range of 30-250 MUm leading to porosity up to 51%. Compared to the control cement, Young's modulus and yield strength decreased from 1830 to 740 MPa and from 58 to 23 MPa respectively by adding 7.5 ml bone marrow to 23 ml premixed cement. The polymerization temperature decreased from 61 to 38 ?C for cement modification with 7.5 ml of bone marrow. Setting times of the modified cements were lower in comparison to the regular cement (28 min). Setting times increased with higher amounts of added bone marrow from around 16-25 min. The initial viscosities of the modified cements were higher in comparison to the control cement leading to a lower risk of extravasation. The hardening times followed the same trend as the setting times. In conclusion, blending bone marrow with acrylic bone cement seems to be a promising method to increase the compliance of PMMA cement for use in cancellous bone augmentation in osteoporotic patients due to its modified mechanical properties, lower polymerization temperature and elevated initial viscosity. PMID- 22098907 TI - Ti-Nb-Sn-hydroxyapatite composites synthesized by mechanical alloying and high frequency induction heated sintering. AB - A beta-type Ti-based composite, Ti-35Nb-2.5Sn-15-hydroxyapatite (HA), has been synthesized by mechanical alloying and powder metallurgy. The effects of milling time on microstructure, mechanical properties and biocompatibility of the sintered composites were investigated by scanning electronic microscopy (SEM), X ray diffraction (XRD), microhardness tests, compression tests and cells culture. The results revealed when milling time increased, the homogeneity and relative density of the sintered composite increased, but the finished sintering temperature decreased. The compression Young's modulus of sintered composite from 12 h milled powders was about 22 GPa and its compression strength was 877 MPa. The cell culture results indicated cell viability for these sintered composites was very good. These results revealed the Ti-35Nb-2.5Sn-15HA composite could be useful for medical implants. PMID- 22098909 TI - Influence of the sliding velocity and the applied potential on the corrosion and wear behavior of HC CoCrMo biomedical alloy in simulated body fluids. AB - The corrosion and tribocorrosion behavior of an as-cast high carbon CoCrMo alloy immersed in phosphate buffered solution (PBS) and phosphate buffered solution with bovine serum albumin (PBS+BSA) have been analyzed by electrochemical techniques and surface microscopy. After the electrochemical characterization of the alloy in both solutions, the sample was studied tribo-electrochemically (by open circuit potential, OCP measurements, potentiodynamic curves and potentiostatic tests) in a ball-on-disk tribometer rotating in different sliding velocities. The influence of solution chemistry, sliding velocity and applied potential on the corrosion and tribocorrosion behavior of the CoCrMo alloy has been studied. Anodic current density increases with sliding velocity but wear rate does not change at an applied anodic potential; on the other hand, BSA modifies the wear debris behavior (by agglomerating the debris formed by mechanical removal of particles) thus increasing the mechanical wear volume. Under cathodic conditions, cathodic current density also increases during mechanical contact while the wear rate decreases with sliding velocity and BSA lubricates the contact thus reducing the total wear volume with respect to the non-containing BSA solution. The work shows how the electrode potential critically affects the corrosion and tribocorrosion rates by increasing the wear coefficients at applied anodic potentials due to severe wear accelerated corrosion. PMID- 22098910 TI - Cell adhesion to plasma electrolytic oxidation (PEO) titania coatings, assessed using a centrifuging technique. AB - The adhesion of bovine chondrocytes and human osteoblasts to three titania-based coatings, formed by plasma electrolytic oxidation (PEO), was compared to that on uncoated Ti-6Al-4V substrates, and some comparisons were also made with plasma sprayed hydroxyapatite (HA) coatings. This was done using a centrifuge, with accelerations of up to 160,000 g, so as to induce buoyancy forces that created normal or shear stresses at the interface. It is shown that, on all surfaces, it was easier to remove cells under normal loading than under shear loading. Cell adhesion to the PEO coatings was stronger than that on Ti-6Al-4V and similar to that on HA. Cell proliferation rates were relatively high on one of the PEO coatings, which was virtually free of aluminium, but low on the other two, which contained significant levels of aluminium. It is concluded that the Al-free PEO coating offers promise for application to prosthetic implants. PMID- 22098911 TI - Principal stiffness orientation and degree of anisotropy of human osteons based on nanoindentation in three distinct planes. AB - Haversian systems or 'osteons' are cylindrical structures, formed by bone lamellae, that make up the major part of human cortical bone. Despite their discovery centuries ago in 1691 by Clopton Havers, their mechanical properties are still poorly understood. The objective of this study is a detailed identification of the anisotropic elastic properties of the secondary osteon in the lamella plane. Additionally, the principal material orientation with respect to the osteon is assessed. Therefore a new nanoindentation method was developed which allows the measurement of indentation data in three distinct planes on a single osteon. All investigated osteons appeared to be anisotropic with a preferred stiffness alignment along the axial direction with a small average helical winding around the osteon axis. The mean degree of anisotropy was 1.75+/ 0.36 and the mean helix angle was 10.3 degrees +/-0.8 degrees . These findings oppose two well established views of compact bone microstructure: first, the generally clear axial stiffness orientation contradicts a regular 'twisted plywood' collagen fibril orientation pattern in lamellar bone that would lead to a more isotropic behavior. Second, the class of transverse osteons were not observed from the mechanical point of view. PMID- 22098912 TI - Correlations between age, prestrain, diameter and atherosclerosis in the male abdominal aorta. AB - The longitudinal prestrain of arteries facilitates their physiological function. Remodeling, adaptation and aging result in an age-dependent magnitude of the pretension. Although the phenomenon is known, detailed statistics, especially for human arteries, are lacking. This study was designed to propose the regression model capable of estimating the prestrain of the human abdominal aorta. The length of the abdominal aorta before, l, and after excision from the body, L, the diameter, heart weight, thickness of left ventricle and degree of atherosclerosis were collected in autopsies of 156 male cadavers of known age. Longitudinal prestrain was quantified by means of the stretch ratio lambda=l/L. Statistical analysis revealed significant dependence between age, prestrain, diameter and atherosclerosis, which were best fitted to the power law equation. Longitudinal prestretch reduced with age significantly; lambdamean=1.30+/-0.07 for age<30 (n=29), whereas lambdamean=1.06+/-0.03 for age>59 (n=31) with p-value<0.0001. Raw data gave linear correlation coefficients as follows: lambda-age (R=-0.842); l age (R=0.023); L-age (R=0.476); (l-L)-age (R=-0.811). It was concluded that longitudinal prestrain decreases nonlinearly with age and both age and diameter are suitable predictors of the prestrain. Data suggests that unloaded length elongates with age in contrast to the elastic retraction. PMID- 22098913 TI - Thiel-fixation preserves the non-linear load-deformation characteristic of spinal motion segments, but increases their flexibility. AB - Human cadaveric specimens are recommended as the best option for in-vitro tests. However, fresh human spine specimens are often difficult to obtain. Further problems are the potential risk of infection and they can only be used over a limited test period. Therefore, the use of embalmed specimens is often discussed. The most common method is formalin fixation. However, this type of embalming can result in failure, because the biomechanical properties of the tissue is partially influenced. In recent years the development of the new method, the fixation according to Thiel, could provide an alternative to fresh or formalin fixed specimens. The aim of the present study is to compare the biomechanical properties between fresh and Thiel-fixed spine specimens, and to compare the data to previous data of a test with formalin fixation. For the study, six L1-L2 spinal segments from 16-week-old calves were biomechanically tested. The parameters, range of motion and neutral zone, were determined in flexion/extension, right/left lateral bending and left/right axial rotation. The results showed that the specimens kept their non-linear load-deformation characteristic after Thiel fixation. The range of motion of Thiel-fixed specimens increased relative to the unembalmed state by approximately 22% in flexion extension, 23% in lateral bending (p<0.05) and 45% in axial rotation (p<0.05). In conclusion, the results still suggest a preference for fresh cadaveric spine specimens for quantitative biomechanical in-vitro testing, because they provide the best physiological conditions. However, for preliminary tests, which may only be used for orientation, embalmed specimens using the Thiel fixation method might serve as an alternative. Compared to formalin-fixated specimens which become approximately 5 times stiffer and completely lose their non-linear load deformation-characteristic, as found in a previous study; the Thiel fixation maintains the non-linear load-deformation-characteristic but increases the range of motion. PMID- 22098914 TI - Contraction behaviors of dental composite restorations--finite element investigation with DIC validation. AB - The objective of this study was to examine the effects of cavity configuration on the polymerization shrinkage and stress of light-cured composite restorations by combining local strain measurement and a finite element analysis (FEA). Dental mesio-occluso-distal cavities of various widths and depths (each for 2 vs. 4 mm), representing different configuration factors, were prepared on extracted molars. The displacements of the bonded tooth cusps and cavity floors, caused by polymerization shrinkage of composite restorations, were assessed utilizing a digital-image-correlation (DIC) technique. The cervical marginal microleakage was investigated by examining the resin replicas of these restorations under SEM. The local material properties of the polymerized composite along the curing depth were defined by the nanoindentation test and applied in the subsequent FEA. In the FEA, four models were generated to correspond with the experimental restorations. In the DIC measurement results, the 4(w)*4(D) mm cavity presented the greatest values of inward displacements at the cusp and floor. The cavity depth, rather than the cavity width, was found to significantly correlate to the floor deformation, the location of shrinkage centers, and also the cervical microleakage ratio. The FEA simulation results showed that the 2(w)*4(D) mm cavity presented the maximal von Mises and principal stress located respectively on the cervical margins and cavity floor. Additional safety factor analysis showed a high risk of bond failure over the cavity floor in the 4-mm deep cavity. With the experimental validation, the simulation revealed that the cavity depth was significant to the formation of contraction stress and the incidence of interfacial debonding. PMID- 22098915 TI - The effect of sintering temperature on the microstructure and mechanical properties of a bioceramic bone scaffold. AB - Micro and nanostructural properties are believed to play a critical role in the osteoinductive capacity of bioceramic bone scaffolds. Physical characteristics also play an important role for optimum biological performance, including osteoconductivity and strength. In this study microstructural and nano-mechanical properties of a bioceramic bone scaffold were investigated as a function of the sintering temperature in the range of 950-1150 degrees C, through the use of scanning electron microscopy (SEM), X-ray diffraction (XRD) and nanoindentation testing. Although the samples presented the same crystallographic phase, an increase in sintering temperature resulted in increased grain size, density and crystallite size. The intrinsic mechanical properties were measured by nanoindentation testing and analyzed with the Oliver-Pharr method. The nanoindentation tests consisted of a series of fourteen partial unload tests (n=14 per treatment) of twelve steps ranging from 1 to 12 mN. Statistically significant increases in hardness and elastic modulus were measured for increasing sintering temperature. These results support the development of clinically successful bioceramic scaffolds with mechanical properties that encourage bone ingrowth and provide structural integrity. PMID- 22098916 TI - Elasticity and viscoelasticity of embolization microspheres. AB - The present study investigates the mechanical properties of three embolization microspheres (E-ms): tris-acryl gelatin microspheres (TG-ms), acrylamido polyvinyl alcohol microspheres (APVA-ms), and polyphosphazene-coated polymethylmethacrylate microspheres (PP-PMMA-ms). Compression and relaxation tests were performed on monolayers of particles and their Young's moduli and relaxation half times (RHTs) were determined. The elasticity of E-ms was evaluated by applying Hertz theory with the assumptions of incompressibility and a Poisson's ratio of 0.5. The Young's moduli of TG-ms, APVA-ms, and PP-PMMA-ms were 39.6+/-5.05 kPa, 18.8+/-4.00 kPa, and 13.6+/-1.98 kPa, respectively. The RHTs of TG-ms, APVA-ms, and PP-PMMA-ms were 52.3+/-5.56 s, 59.1+/-8.16 s, and 31.0+/-7.01 s, respectively. TG-ms have a high rigidity and deform slightly under a sustained compression since they have a high elasticity. PP-PMMA-ms are soft and deform a lot under sustained compression. They are more viscous than the other two microspheres. APVA-ms have intermediate material properties, having the same low rigidity as PP-PMMA-ms and being more elastic than TG-ms. PMID- 22098917 TI - Arsenic, cadmium and neuron specific enolase (ENO2, gamma-enolase) expression in breast cancer. AB - BACKGROUND: Neuron specific enolase (ENO2, gamma-enolase) has been used as a biomarker to help identify neuroendocrine differentiation in breast cancer. The goal of the present study was to determine if ENO2 expression in the breast epithelial cell is influenced by the environmental pollutants, arsenite and cadmium. Acute and chronic exposure of MCF-10A cells to As+3 and Cd+2 sufficient to allow colony formation in soft agar, was used to determine if ENO2 expression was altered by these pollutants. RESULTS: It was shown that both As+3 and Cd+2 exposure caused significant increases in ENO2 expression under conditions of both acute and chronic exposure. In contrast, ENO1, the major glycolytic enolase in non-muscle and neuronal cells, was largely unaffected by exposure to either As+3 or Cd+2. Localization studies showed that ENO2 in the MCF-10A cells transformed by As+3 or Cd+2 had both a cytoplasmic and nuclear localization. In contrast, ENO1 was localized to the cytoplasm. ENO2 localized to the cytoplasm was found to co-localized with ENO1. CONCLUSION: The results are the first to show that ENO2 expression in breast epithelial cells is induced by acute and chronic exposure to As+3 or Cd+2. The findings also suggest a possible link between As+3 and Cd+2 exposure and neuroendocrine differentiation in tumors. Overall, the results suggest that ENO2 might be developed as a biomarker indicating acute and/or chronic environmental exposure of the breast epithelial cell to As+3 and Cd+2. PMID- 22098918 TI - Dietary treatments enriched in olive and safflower oils regulate seric and placental matrix metalloproteinases in maternal diabetes. AB - OBJECTIVES: Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in placental development and function, although related to the pro-inflammatory environment when produced in excess. Previous studies have identified MMP-2 and MMP-9 overactivities in the placenta from diabetic rats. In this study, we aimed to determine whether diets supplemented with olive and safflower oil, enriched in natural PPAR ligands, are able to regulate MMP-2 and MMP-9 activities in the placenta and serum from diabetic rats. STUDY DESIGN: Diabetes was induced in rat neonates by streptozotocin administration (90mg/kg s.c.). Control and diabetic rats were fed with 6% olive oil- or 6% safflower oil-supplemented diets from days 0.5-13.5 of gestation. MAIN OUTCOME MEASURES: On day 13.5 of gestation, placentas and sera were isolated for further determination of matrix metalloproteinases (MMPs) 2 and 9 activities by zymography. Placental MMP-2 and MMP-9 protein concentration and immunolocalization were also determined. RESULTS: Sera from diabetic pregnant animals showed MMP-2 and MMP-9 overactivities when compared to controls. Serum MMP-9 activity was significantly decreased when the diabetic animals received the olive and safflower oil dietary treatments. Placentas from diabetic rats showed increased MMP-2 and MMP-9 activities and protein concentrations, and both were decreased when diabetic rats received the olive and safflower dietary treatments. CONCLUSIONS: This study demonstrates that both olive and safflower oil-supplemented diets were able to prevent MMPs overactivities in the placenta from diabetic rats, and that these beneficial effects are reflected in rat sera. PMID- 22098919 TI - A potassium channel opener for neuropathy, motor neuron disease and beyond. PMID- 22098920 TI - Clinical ramifications of bronchial kink after upper lobectomy. AB - BACKGROUND: Bronchial kink is caused by upward displacement of the remaining lower lobe of the lung after upper lobectomy, which can cause an intractable cough or shortness of breath. However, bronchial kink is often overlooked because of the difficulty in the simultaneous diagnosis of bronchial curvature and narrowing. METHODS: Screening for bronchial kink with three-dimensional computed tomography (CT)-based bronchography was done on 50 patients who had undergone hemilateral upper lobectomy for cancer. Bronchial kink was confirmed if there was airway angulation and resultant stenosis exceeding 80%. We compared postoperative changes in spirometry-based ventilatory capacity with CT-based functional lung volume (FLV) in patients with and without bronchial kink. RESULTS: Bronchial kink was confirmed in 21 patients (42%). Postoperative FLV and ventilatory capacity were significantly greater in patients without than in those with bronchial kink (p<0.05 for both measures). Postoperative FLV and ventilatory capacity were also significantly greater than the estimated postoperative values for both measures in patients without bronchial kink (both, p<0.05), representing favorable compensatory adaptation of the remaining lung, whereas this was not the case in patients with bronchial kink (both, p>0.1). Patients with bronchial kink complained more often than those without bronchial kink of an intractable cough and shortness of breath (76% vs 21%, respectively, p<0.01). CONCLUSIONS: Bronchial kink after upper lobectomy is a common and functionally unfavorable condition that can exacerbate postoperative shortness of breath. Computed tomography-based bronchography is a useful tool in screening for bronchial kink. Strategies for preventing bronchial kink should be explored in the clinical setting. PMID- 22098921 TI - Coronary artery disease in adult congenital heart disease: outcome after coronary artery bypass grafting. AB - BACKGROUND: Atherosclerotic coronary artery disease may be seen during repair of adult congenital heart disease (ACHD). There are few data outlining outcomes of concomitant coronary artery bypass grafting (CABG) in these patients. METHODS: Between February 1972 and August 2009, 122 patients (77 men) underwent concomitant CABG at the time of ACHD repair; median age was 64 years (range 40 to 85 years). Thirty patients (25%) had preoperative angina, 7 patients (6%) had previous myocardial infarction (MI), and 6 patients (5%) had previous percutaneous intervention. Most common primary cardiac diagnoses included secundum atrial septal defect (ASD) in 73 patients (60%), Ebstein's anomaly in 14 patients (11%), and partial anomalous pulmonary venous connection in 8 patients (7%). RESULTS: Operations included ASD repair in 78 patients (64%), tricuspid/pulmonary valve procedures in 23 patients (19%), and ventricular septal defect repair in 10 patients (8%). One bypass graft procedure was performed in 69 patients (57%), 2 bypass graft procedures were performed in 32 patients (26%), 3 bypass graft procedures were performed in 14 patients (11%), 4 bypass graft procedures were performed in 5 patients (4%), and 5 bypass graft procedures were performed in 2 patients (2%). There were 4 early deaths (3.3%). During a median follow-up of 6 years (maximum follow-up, 32 years), actuarial survival was 76% at 5 years and 56% at 10 years. In patients with left anterior descending (LAD) artery disease, survival was higher when a left internal mammary graft (LIMA) was used (5 years, 86% versus 66%; 10 years, 66% versus 36%; p<0.05). CONCLUSIONS: Concomitant CABG may be required at the time of correction of ACHD. Survival is higher when a LIMA graft is used, and late functional outcome is good, with a low incidence of late angina and need for reintervention. PMID- 22098922 TI - Fifteen-year outcome of laparoscopic and open Nissen fundoplication: a randomized clinical trial. AB - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has become the method of choice in the surgical treatment of gastroesophageal reflux disease (GERD), replacing its open counterpart without confirmation by the long-term results of controlled clinical studies. The goal of the present study was to compare the 15 year outcome of a randomized controlled comparison study of LNF versus open Nissen fundoplication (ONF). METHODS: From 1992 to 1995, 110 consecutive patients were randomized to undergo LNF or ONF. The 15-year objective results were evaluated by endoscopy, and the subjective symptomatic outcome was assessed by interviews. RESULTS: A total of 86 patients (48 in the LNF [LAP] and 38 in the ONF [OPEN] group) participated in the study. The late long-term symptomatic outcome was similar in the two patient groups. In the LAP group, 91.7% of the patients gave a positive evaluation of their surgical result, as compared with 76.3% of the patients in the OPEN group (p=0.0484). A significantly greater number of disrupted plications (p=0.0115) and incisional hernias (p<0.001) occurred in the OPEN than in the LAP group. Both the subjective outcome and the objective endoscopic and clinical findings in the present study were in accord with our previously reported outcomes at 11-years after laparoscopic versus open fundoplication. The study found a trend toward (p=0.0851) an increasing need for the regular use of a proton pump inhibitor with the passage of time after Nissen fundoplication. CONCLUSIONS: The 15-year results obtained in the present study define laparoscopic Nissen fundoplication as the procedure of choice in the surgical management of GERD. The long-term symptomatic outcomes of open and laparoscopic Nissen fundoplication appear to remain unaltered after the first 10 postoperative years. PMID- 22098923 TI - Genetic diversity and mycotoxin production of Fusarium lactis species complex isolates from sweet pepper. AB - An internal fruit rot disease of sweet peppers was first detected in Belgium in 2003. Research conducted mostly in Canada indicates that this disease is primarily caused by Fusarium lactis Pirotta. Ninety-eight Fusarium isolates obtained from diseased sweet peppers from Belgium, as well as from other countries (Canada, the Netherlands and the United Kingdom) were identified by sequencing the translation elongation factor 1alpha (EF). Of these 98 isolates, 13 were identified as F. oxysporum Schltdl., nine as F. proliferatum (Matsush.) Nirenberg and two belonged to clade 3 of the F. solani species complex. Of the 74 remaining isolates, the EF sequence showed 97% to 98% similarity to F. lactis. Of these isolates, the beta-tubulin (TUB), calmodulin (CAM) and the second largest subunit of RNA polymerase II (RPB2) genes were also sequenced. Analysis of the combined sequences revealed that the 74 isolates share nine combined sequences that correspond to nine multilocus sequence types (STs), while the F. lactis neotype strain and one other strain, both isolated from figs, form a separate ST. Together, these 10 STs represent a monophyletic F. lactis species complex (FLASC). An unusually high level of genetic diversity was observed between (groups of) these STs. Two of them (ST5 and ST6) fulfilled the criteria for species recognition based on genealogical exclusivity and together represent a new monophyletic species lineage (FLASC-1). The seven other STs, together with the F. lactis neotype ST, form a paraphyletic species lineage in the African clade of the Gibberella fujikuroi species complex (GFSC). From each of the 10 STs, the mycotoxin production was assessed using a multi-mycotoxin liquid chromatography mass spectrometry method. Out of the 27 analyzed mycotoxins, beauvericin and fumonisins were detected in sweet pepper tissue and in maize kernels. The 10 STs clearly differed in the amount of mycotoxin produced, but there was only limited congruence between the production profile and the phylogenetic analysis. Furthermore, the morphological characterization (based on mycelial growth rate and the length of macroconidia) showed distinct differences between the 10 STs, but again there was limited congruence with the phylogenetic results. In conclusion, the data presented in this study demonstrate that 75% of the isolates obtained from sweet pepper with internal fruit rot belong to a F. lactis species complex (FLASC), including a new FLASC-1 monophyletic species, and that the members of this complex display great genetic and phenotypic diversity. PMID- 22098924 TI - Predictors of hospitalized patients' intentions to prevent healthcare harm: a cross sectional survey. AB - BACKGROUND: Patients can play an important role in reducing healthcare harm but little is known about the factors that may affect patients' willingness to participate. In order to encourage the 'active' patient it is critical that we gain a deeper understanding of the antecedents of safety-relevant behaviours. Doing this will enable the implementation of effective interventions aimed at supporting patients to work with healthcare professionals in ensuring safe care. OBJECTIVE: To examine predictors of patients' intentions to engage in two safety behaviours: (1) reminding healthcare staff to wash their hands and; (2) notifying healthcare staff if they are not wearing a hospital identification bracelet. DESIGN: Cross-sectional survey study. PARTICIPANTS: A purposive sampling method was employed to recruit 80 medical and surgical hospital inpatients aged 18-80 (mean 48) from one inner city London teaching hospital. METHODS: A 42 item survey that measured the extent that patients' control beliefs, behavioural beliefs, normative beliefs and perceived susceptibility and severity towards a hospital acquired infection or a misidentification error could predict their intentions to ask doctors/nurses about their hand washing compliance or notify doctors/nurses if they are not wearing a hospital identification bracelet. Data was analysed using multiple regression analysis. RESULTS: Control beliefs, normative beliefs and perceived severity were the strongest predictors of patients' intentions to participate in both behaviours. The regression models accounted for a smaller percentage of the variance in patients' intentions to ask doctors/nurses if they have washed their hands (42%/37%) than notifying staff if they were not wearing an identification bracelet (54%/56%). CONCLUSIONS: If patients understand why a behaviour is beneficial, they perceive it as acceptable to participate in and that they have control over the decision to engage in the behaviour, we hypothesise that more patients will intend to participate in that behaviour. When designing interventions aimed at encouraging the participation of patients in promoting their own safety, consideration should be given to the potential influence of patients' control beliefs, normative beliefs and perceived severity of errors on their intentions to participate. PMID- 22098925 TI - Reflections on the ethics of internet newsgroup research. PMID- 22098926 TI - The impact of term-time paid work on academic performance in nursing students: a longitudinal study. AB - BACKGROUND: Nursing students in higher education are spending more time in paid employment despite evidence that this can impact negatively on academic performance. OBJECTIVES: To examine the effect of paid work on academic performance in undergraduate nursing students. DESIGN: Descriptive, correlational survey with longitudinal follow-up. PARTICIPANTS: Nursing students in metropolitan Sydney, Australia. METHODS: First year nursing students surveyed at baseline were followed up at the end of the final year of their nursing program to examine factors influencing academic performance. RESULTS: Of the 566 Year 1 nursing students who were surveyed in the second semester of their Bachelor of Nursing program, 182 students (32%) completed the follow-up survey in Year 3. The percentage of students engaging in paid work during term-time had increased (p<0.001), from 70% in Year 1 to 84% in Year 3. There was an inverse relationship between mean hours in paid work during term-time and nursing students' GPA in their final year. Taking into account demographic factors, the mean hours spent in paid work during term-time had a negative impact on nursing students' GPA (p<0.001). CONCLUSION: In view of these findings, we suggest that new models of undergraduate nursing education be explored to include faculty approved nursing related employment with defined opportunities for learning. This would accommodate the dual roles of undergraduate nursing students as students and employees and therefore not endanger their academic performance. PMID- 22098927 TI - Mixed brominated/chlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls: Simultaneous congener-selective determination in food. AB - Of the 4600 individual poly-halogenated (bromo-chloro) dibenzo-p-dioxins, dibenzo furans (PXDD/Fs) and 9180 poly-halogenated biphenyls (PXBs), 19 compounds were selected for analysis in food, based on current toxicological knowledge, chemical configuration, type and degree of halogenation, and the limited knowledge on environmental occurrence levels. The selection was also tempered by the availability of reliable analytical standards. The analytical methodology designed to allow simultaneous determination of PXDD/Fs and PXBs, was based on internal standardisation with (13)C(12) labelled compounds and high resolution mass spectrometry and involved a new separation procedure using dual activated carbon column fractionation. In order to unambiguously measure these compounds a practical, higher mass resolution (13,500-15,000 res) was used, coupled with a judicious choice of analyte ions and relative ion ratios. Further specificity was incorporated by exploiting the differences in chromatographic retention from those of potential interferants. The methodology was validated and used to measure occurrence levels of these contaminants in different matrices such as milk, meat, fish, eggs, offal, shellfish and soil. The limits of detection achieved by this methodology ranged from 0.005 to 0.02ngkg(-1) fat for foods. The analyses revealed the presence of both PXDD/Fs and PXBs, with the latter occurring to a greater extent, followed by PXDFs. This work represents the first targeted approach to measuring a range of individual PXDD/Fs and PXBs simultaneously. PMID- 22098928 TI - Food contaminant analysis at high resolution mass spectrometry: application for the determination of veterinary drugs in milk. AB - Veterinary drugs (VDs) can remain in milk as a consequence of their use in livestock. In order to control the levels of VD residues in milk, screening methodologies can be applied for a rapid discrimination among negative and non negative samples. In a second stage, non-negative samples are classified as negative or positive samples by using a confirmation method. Pre-target screening methods in low resolution MS (LRMS) are normally applied, but the number of analytes is limited, whereas the information obtained by full scan acquisition in high resolution mass spectrometry (HRMS) is improved. Here, three screening methods (running time<4 min) based on Orbitrap, quadrupole-time of flight (QqTOF) and triple quadrupole (QqQ) have been compared, using in all cases ultra-high performance liquid chromatography (UHPLC). For HRMS, the identification of the VDs was based on retention time (RT) and accurate mass measurements. Confirmation was based on the monitoring of fragments generated without precursor selection. The performance characteristics of the screening method provided reliable information regarding the presence or absence of the compounds below an established value, including uncertainty region and cut-off values. Better results in terms of cut-off values (<= 5.0 MUg kg(-1), except for spiramycin with a cut-off of 13.4 MUg kg(-1) for milk samples and 43.1 MUg kg(-1) for powdered milk based, emamectin with a cut-off of 42.2 MUg kg(-1) for milk samples and doxycycline, with a cut-off value of 15.8 MUg kg(-1) in powdered milk-based infant formulae) and uncertainty region were obtained using the Orbitrap-based screening method, which was submitted to further validation and used to analyze different real milk samples. The proposed method can be used in routine analysis, providing reliable results. PMID- 22098929 TI - Use of cation exchange chromatography for human C-peptide isotope dilution - mass spectrometric assay. AB - An application of ion exchange chromatography for C-peptide analysis is described here. At the stage of C-peptide isolation, a strong cation exchanger (SP HP or MonoS) was used to purify the analyte from ballast proteins and peptides. The conditions of ion-exchange chromatographic separations were optimized using theoretical modeling of the net surface electric charge of the peptide as a function of pH. The purified and concentrated sample was further subjected to LC MS/MS. In order to improve the reliability of analysis, two fragment ions were monitored simultaneously both for native C-peptide and internal standard, isotopically labeled C-peptides analogues (fragments with m/z of 927.7 and 147.2). Using ion-exchange chromatography, it became possible to process larger sample volumes, important for testing patients with very low C peptide levels, compared to currently used solid phase extraction methods. PMID- 22098930 TI - Hydrophilic interaction chromatography of seized drugs and related compounds with sub 2 MUm particle columns. AB - The use of hydrophilic interaction chromatography (HILIC) with sub 2 MUm particle columns for the analysis of drugs and related compounds of forensic interest is described. This technique uses a high organic/low aqueous buffered mobile phase with a polar stationary phase, and is excellent for the separation of many of the charged solutes that are found in forensic drug exhibits. In this study, HILIC is investigated for 11 solutes of forensic interest, including weak bases, weak acids, and a neutral solute. In addition, for columns containing either ethylene bridged hybrid particles with or without an amide bonded phase, the effects of acetonitrile concentration, buffer type, buffer concentration, linear velocity, and sample concentration were studied. Based on these studies, HILIC with sub 2 MUm particle columns can offer highly efficient, selective, and rapid isocratic separations of drugs and related compounds of forensic interest, with excellent peak shapes and low back pressures. This is in contrast to reverse phase chromatography (RPLC), where gradient elution is usually required, which can result in extensive overlap between acidic, neutral, and basic solutes. In addition, since HILIC exhibits a much greater loading capacity than RPLC, it could be a preferred technique for drug profiling. Furthermore, because high organic content mobile phases are highly amenable to mass spectrometric detection, the use of HILIC with tandem mass spectrometric detection for the analysis of seized drugs is described. PMID- 22098931 TI - Selective displacement chromatography in multimodal cation exchange systems. AB - A library of displacer analogues with varying degrees of electrostatic, hydrophobic and hydrogen bonding moieties was evaluated for their ability to enhance the selectivity of multimodal (MM) chromatography under high loading conditions. The library was screened for displacement of model proteins using a robotic liquid handling system and selective batch separations were achieved for proteins that were inseparable with linear gradient chromatography. Trends in protein displacement were identified and displacers with higher hydrophobicity and net charge exhibited improved protein displacements. Proteins that interacted with the resins primarily via electrostatic interactions were more readily displaced than those that possessed a significant hydrophobic contribution to their binding. In addition, multimodal displacers were found to be more selective than single mode electrostatic displacers. Column chromatography studies were also carried out and baseline separations were achieved for model protein pairs using selective displacement. Finally, operation of these columns in the desorption mode resulted in baseline separation of model proteins which were not separable by selective displacement chromatography. This study indicates that the inherent selectivity of MM resins can be augmented by the selectivity of the displacer under non-linear competitive binding conditions, creating new opportunities for protein separations not possible using traditional gradient operations. PMID- 22098932 TI - Enantioseparation of (+/-)-threo-methylphenidate in human plasma by cyclodextrin modified sample stacking capillary electrophoresis. AB - The (+/-)-threo-methylphenidate ((+/-)-threo-MP) is widely used for treatment of attention-deficit hyperactivity disorder (ADHD). According to clinical evidence, (+)-threo-MP possesses higher potency than (-)-threo-MP. Due to ppb level in plasma, till now, none of the capillary electrophoresis (CE) methods have been able to provide adequate sensitivity for therapeutic (+/-)-threo-MP monitoring. In this study, a cyclodextrin-modified field-amplified sample stacking CE method (CD-FASS-CE) for enantioseparation of (+/-)-threo-MP in human plasma was established for clinical applications. Phosphate buffer (50mM, pH 3.0) was filled into uncoated fused silica capillary (40 cm, 50 MUm I.D.), followed by a water plug (0.5 psi, 10s). Electrokinetic injection (6 kV, 200 s) was used to load samples and to enhance sensitivity. Stacking and separation were performed at 20 kV and 200 nm using phosphate buffer (50mM, pH 3.0) containing 20mM HP-beta-CD and 30 mM triethanolamine. Analytes were separated simultaneously by using CD FASS-CE and had a lower detection limit of equal to the sub-ppb level. Linear calibration curves were obtained from 1 to 80 ng/mL (r=0.998). The limit of detection for both isomers was 600 pg/mL. RSD and RE of precision and accuracy in intra- and inter-day assays were below 7.89%. This method was further applied to analyze (+/-)-threo-MP in four healthy Asian volunteers and that provided some relevant information for clinical treatments. PMID- 22098933 TI - Phase transfer membrane supported liquid-liquid-liquid microextraction combined with large volume sample injection capillary electrophoresis-ultraviolet detection for the speciation of inorganic and organic mercury. AB - In this paper, a novel sample pretreatment technique termed phase transfer based liquid-liquid-liquid microextraction (PT-LLLME) was proposed for the simultaneous extraction of inorganic and organic mercury species. In PT-LLLME, an intermediate solvent (acetonitrile) was added into the donor phase to improve the contacting between target mercury species and complexing reagent. Meanwhile, a membrane supported (MS)-LLLME unit was designed to realize the PT-LLLME procedure. By using nylon membrane as supporting carrier, larger than 50 MUL of acceptor solution could be hung up. Following PT/MS-LLLME, the acceptor solutions were directly analyzed by large volume sample stacking capillary electrophoresis/ultraviolet detection (LVSS-CE/UV). Accordingly, a new method of PT/MS-LLLME combined with LVSS-CE/UV was developed for the simultaneous speciation of inorganic and organic mercury species. Parameters affecting the extraction efficiency of PT/MS-LLLME were investigated in details. Under the optimized conditions, enrichment factors (EFs) ranging from 160- to 478-fold were obtained for the extraction of target mercury species by PT/MS-LLLME. By combining PT/MS-LLLME with LVSS-CE/UV, EFs were magnified up to 12,138-fold and the limits of detection (at a signal-to-noise ratio of 3) were at sub ppb level. The established approach of PT/MS-LLLME-LVSS-CE/UV was successfully applied to simultaneous determination of inorganic and organic mercury species in biological samples and environmental water samples. PMID- 22098934 TI - Separation of small inorganic anions using methacrylate-based anion-exchange monolithic column prepared by low temperature UV photo-polymerization. AB - A methacrylate-based anion-exchange monolithic column was prepared by a single step UV photo-copolymerization of [2-(methacryloyloxy)ethyl]-trimethyl ammonium chloride, butylmethacrylate, and ethylene dimethacrylate at a low temperature of 15 degrees C. The anion-exchange column exhibited good separation efficiency for the small inorganic anions of NO(2)(-), Br(-), NO(3)(-), and I(-) in the isocratic mode. Under the conditions optimized using a mobile phase of 50% ACN containing 100mM of NaCl, the theoretical plate heights of the anions were within the range of 12.2-15.6 MUm (N, 64,000-82,000 m(-1); k, 0.2-1.6); and a value of 9.4 MUm (N, 110,000 m(-1)) was achieved for t(0). The flow resistance of the column was acceptably low with a permeability of 2.7 * 10(-13) m(2). Fast gradient elution at a flow rate of 32 mm/s resulted in rapid and precise separation of the inorganic anions of IO(3)(-), NO(2)(-), Br(-), NO(3)(-), and I( ) within 20s. PMID- 22098935 TI - Investigation of the biotransformation pathway of verapamil using electrochemistry/liquid chromatography/mass spectrometry - a comparative study with liver cell microsomes. AB - The biotransformation pathway of verapamil, a widely prescribed calcium channel blocker, was investigated by electrochemistry (EC) coupled online to liquid chromatography (LC) and electrospray mass spectrometry (ESI-MS). Mimicry of the oxidative phase I metabolism was achieved in a simple amperometric thin-layer cell equipped with a boron-doped diamond (BDD) working electrode. Structures of the electrochemically generated metabolites were elucidated on the basis of accurate mass data and additional MS/MS experiments. We were able to demonstrate that all of the most important metabolic products of the calcium antagonist including norverapamil (formed by N-demethylation) can easily be simulated using this purely instrumental technique. Furthermore, newly reported metabolic reaction products like carbinolamines or imine methides become accessible. The results obtained by EC were compared with conventional in vitro studies by conducting incubations with rat as well as human liver microsomes (RLMs, HLMs). Both methods showed good agreement with the data from EC/LC/MS. Thus, it can be noted that EC is very well-suited for the simulation of the oxidative metabolism of verapamil. In summary, this study confirms that EC/LC/MS can be a powerful tool in drug discovery and development when applied complementary to established in vitro or in vivo approaches. PMID- 22098936 TI - Editorial on "Technology trends in antibody purification" by P.S. Gagnon. PMID- 22098937 TI - Non-targeted analysis of wastewater treatment plant effluents by high performance liquid chromatography-time slice-solid phase extraction-nuclear magnetic resonance/time-of-flight-mass spectrometry. AB - Extracts of effluents from two different wastewater treatment plants (WWTP) in Switzerland taken during the application period of pesticides were examined by coupling an HPLC-MS system to a nuclear magnetic resonance spectrometer using a post column peak trapping device. By trapping 1 min portions of the chromatogram onto post column solid phase extraction cartridges (time slice-SPE-NMR) a comprehensive overview of proton carrying constituents could be achieved. Non supervised statistical analysis of the NMR spectra obtained by this approach revealed NMR resonances pointing to contaminants present in decreasing proton concentration in the extracts. Comparison of exact mass data acquired during the trapping process to these NMR resonances enabled the identification of the pesticides Linuron, Metazachlor, Ethofumesate, Isoproturon, Metamitron, Propazine and Chloridazon. Desaminometamitron, a known transformation product of Metamitron could also be identified together with unexpected highly concentrated C8, C10 and C12 fatty acids and their glycerol mono- and di esters. Other compounds identified were a drug metabolite (3-Carboxymefenamic acid), a sun screen agent (Ensulizole: 2-Phenyl-1H-1,3-benzodiazole-6-sulfonic acid) and industrial chemicals (Benzotriazole, N-Benzyl-indole). In addition, a number of well resolved proton spectra cannot be attributed to a mass response showing the need of further investigations using 2D-NMR and different ionization techniques. PMID- 22098938 TI - Relative contributions of osteogenic tissues to new bone formation in periosteal distraction osteogenesis: histological and histomorphometrical evaluation in a rat calvaria. AB - BACKGROUND: The relative contributions of different, potential factors to new bone formation in periosteal distraction osteogenesis are unknown. PURPOSE: The aim of the present study was to assess the influence of original bone and periosteum on bone formation during periosteal distraction osteogenesis in a rat calvarial model by means of histology and histomorphometry. METHODS: A total of 48 rats were used for the experiment. The contribution of the periosteum was assessed by either intact or incised periosteum or an occlusive versus a perforated distraction plate. The cortical bone was either left intact or perforated. Animals were divided in eight experimental groups considering the three possible treatment modalities. All animals were subjected to a 7-day latency period, a 10-day distraction period and a 7-day consolidation period. The newly formed bone was analyzed histologically and histomorphometrically. RESULTS: New, mainly woven bone was found in all groups. Differences in the maximum height of new bone were observed and depended on location. Under the distraction plate, statistically significant differences in maximum bone height were found between the group with perforations in both cortical bone and distraction plate and the group without such perforations. CONCLUSIONS: If the marrow cavities were not opened, the contribution to new bone formation was dominant from the periosteum. If the bone perforations opened the marrow cavities, a significant contribution to new bone formation originated from the native bone. PMID- 22098940 TI - Quantitative trait loci mapping of dark-induced senescence in winter wheat (Triticum aestivum). AB - In order to explore the genetics of dark-induced senescence in winter wheat (Triticum aestivum L.), a quantitative trait loci (QTL) analysis was carried out in a doubled haploid population developed from a cross between the varieties Hanxuan 10 (HX) and Lumai 14 (LM). The senescence parameters chlorophyll content (Chl a+b, Chl a, and Chl b), original fluorescence (Fo), maximum fluorescence level (Fm), maximum photochemical efficiency (Fv/Fm), and ratio of variable fluorescence to original fluorescence (Fv/Fo) were evaluated in the second leaf of whole three-leaf seedlings subjected to 7 d of darkness. A total of 43 QTLs were identified that were associated with dark-induced senescence using composite interval mapping. These QTLs were mapped to 20 loci distributed on 11 chromosomes: 1B, 1D, 2A, 2B, 3B, 3D, 5D, 6A, 6B, 7A, and 7B. The phenotypic variation explained by each QTL ranged from 7.5% to 19.4%. Eleven loci coincided with two or more of the analyzed parameters. In addition, 14 loci co-located or were linked with previously reported QTLs regulating flag leaf senescence, tolerance to high light stress, and grain protein content (Gpc), separately. PMID- 22098939 TI - Transcriptional analysis of late ripening stages of grapevine berry. AB - BACKGROUND: The composition of grapevine berry at harvest is a major determinant of wine quality. Optimal oenological maturity of berries is characterized by a high sugar/acidity ratio, high anthocyanin content in the skin, and low astringency. However, harvest time is still mostly determined empirically, based on crude biochemical composition and berry tasting. In this context, it is interesting to identify genes that are expressed/repressed specifically at the late stages of ripening and which may be used as indicators of maturity. RESULTS: Whole bunches and berries sorted by density were collected in vineyard on Chardonnay (white cultivar) grapevines for two consecutive years at three stages of ripening (7-days before harvest (TH-7), harvest (TH), and 10-days after harvest (TH+10)). Microvinification and sensory analysis indicate that the quality of the wines made from the whole bunches collected at TH-7, TH and TH+10 differed, TH providing the highest quality wines.In parallel, gene expression was studied with Qiagen/Operon microarrays using two types of samples, i.e. whole bunches and berries sorted by density. Only 12 genes were consistently up- or down-regulated in whole bunches and density sorted berries for the two years studied in Chardonnay. 52 genes were differentially expressed between the TH-7 and TH samples. In order to determine whether these genes followed a similar pattern of expression during the late stages of berry ripening in a red cultivar, nine genes were selected for RT-PCR analysis with Cabernet Sauvignon grown under two different temperature regimes affecting the precocity of ripening. The expression profiles and their relationship to ripening were confirmed in Cabernet Sauvignon for seven genes, encoding a carotenoid cleavage dioxygenase, a galactinol synthase, a late embryogenesis abundant protein, a dirigent-like protein, a histidine kinase receptor, a valencene synthase and a putative S adenosyl-L-methionine:salicylic acid carboxyl methyltransferase. CONCLUSIONS: This set of up- and down-regulated genes characterize the late stages of berry ripening in the two cultivars studied, and are indirectly linked to wine quality. They might be used directly or indirectly to design immunological, biochemical or molecular tools aimed at the determination of optimal ripening in these cultivars. PMID- 22098941 TI - Dose reduction in digital breast tomosynthesis (DBT) screening using synthetically reconstructed projection images: an observer performance study. AB - RATIONALE AND OBJECTIVES: The aim of this study was to retrospectively compare the interpretive performance of synthetically reconstructed two-dimensional images in combination with digital breast tomosynthesis (DBT) versus full-field digital mammography (FFDM) plus DBT. MATERIALS AND METHODS: Ten radiologists trained in reading tomosynthesis examinations interpreted retrospectively, under two modes, 114 mammograms. One mode included the directly acquired full-field digital mammograms combined with DBT, and the other included synthetically reconstructed projection images combined with DBT. The reconstructed images do not require additional radiation exposure. The two modes were compared with respect to sensitivity, namely, recommendation to recall a breast with either a pathology-proven cancer (n = 48) or a high-risk lesion (n = 6), and specificity, namely, no recommendation to recall a breast not depicting an abnormality (n = 144) or depicting only benign abnormalities (n = 30). RESULTS: The average sensitivity for FFDM with DBT was 0.826, compared to 0.772 for synthetic FFDM with DBT (difference, 0.054; P = .017 and P = .053 for fixed and random reader effects, respectively). The proportions of breasts with no or benign abnormalities recommended to be recalled were virtually the same: 0.298 and 0.297 for the two modalities, respectively (95% confidence intervals for the difference, -0.028 to 0.036 and -0.070 to 0.066 for fixed and random reader effects, respectively). Sixteen additional clusters of microcalcifications ("positive" breasts) were missed by all readers combined when interpreting the mode with synthesized images versus FFDM. CONCLUSIONS: Lower sensitivity with comparable specificity was observed with the tested version of synthetically generated images compared to FFDM, both combined with DBT. Improved synthesized images with experimentally verified acceptable diagnostic quality will be needed to eliminate double exposure during DBT-based screening. PMID- 22098942 TI - Bureaucracy and the future of residency education. PMID- 22098943 TI - Comparison of digital with film radiographs for the classification of pneumoconiotic pleural abnormalities. AB - RATIONALE AND OBJECTIVES: Analog film radiographs are typically used to classify pneumoconiosis to allow comparison with standard film radiographs. The aim of this study was to determine if digital radiography is comparable to film for the purpose of classifying pneumoconiotic pleural abnormalities. MATERIALS AND METHODS: Subjects were 200 asbestos-exposed patients, from whom digital and film chest radiographs were obtained along with chest high-resolution computed tomographic scans. Using a crossover design, radiographs were independently read on two occasions by seven readers, using conventional International Labour Organization standards for film and digitized standards for digital. High resolution computed tomographic scans were read independently by three readers. Areas under the receiver-operating characteristic curves were calculated using high-resolution computed tomographic ratings as the gold standard for disease status. Mixed linear models were fit to estimate the effects of order of presentation, occasion, and modality, treating the seven readers as a random effect. Comparing digital and film radiography for each reader and occasion, crude agreement and agreement beyond chance (kappa) were also calculated. RESULTS: The linear models showed no statistically significant sequence effect for order of presentation (P = .73) or occasion (P = .28). Most important, the difference between modalities was not statistically significant (digital vs film, P = .54). The mean area under the curve for film was 0.736 and increased slightly to 0.741 for digital. Mean crude agreement for the presence of pleural abnormalities consistent with pneumoconiosis across all readers and occasions was 78.3%, while the mean kappa value was 0.49. CONCLUSIONS: These results indicate that digital radiography is not statistically different from analog film for the purpose of classifying pneumoconiotic pleural abnormalities, when appropriate standards are used. PMID- 22098944 TI - Layperson-oriented vs. clinical-based models for prediction of incidence of ischemic stroke: National FINRISK Study. AB - BACKGROUND: A simplified model not requiring a clinic visit is important for cardiovascular prevention. We compared such a model, with one requiring clinical measurements for prediction of ischemic stroke. METHODS: Five population-based Finnish cohorts comprising 14 296 men and 16 065 women aged 25-64 years were randomly recruited from 1982, and followed up using the national registers until the end of the 2007. The final Cox model included age, prior history of diabetes and hypertension, happy marriage, capability to walk 500 m (self-estimate), regular exercise, vegetable/fruit intake, smoking, body mass index, and systolic blood pressure; the layperson-oriented model was developed by taking blood pressure away from the final model. RESULTS: Four hundred sixty-nine men and 371 women developed ischemic stroke events. The area under the receiver operating characteristic curve (95% confidence interval) for 10 years incidence of ischemic stroke was 0.817 (0.791-0.843) and 0.813 (0.787-0.839) for the model with and without systolic blood pressure in men and 0.815 (0.782-0.848) and 0.812 (0.779 0.844), respectively, in women (P > 0.10). The predicted 10-year events rate matched well with the observed one across deciles of the predicted risk in men (chi(2) = 11.57, 9df, P = 0.239) and in women (chi(2) = 11.18, P = 0.263). The overall net reclassification improvement after adding blood pressure was 8.8% (P = 0.016) in men and 3.2% (P = 0.234) in women. The predicted 10-year risk of the ischemic stroke based on global vascular event models that includes coronary heart diseases did not match well with the observed stroke risk. CONCLUSIONS: The layperson model performed as well as the clinical-based one. PMID- 22098945 TI - The e-Health Implementation Toolkit: qualitative evaluation across four European countries. AB - BACKGROUND: Implementation researchers have attempted to overcome the research practice gap in e-health by developing tools that summarize and synthesize research evidence of factors that impede or facilitate implementation of innovation in healthcare settings. The e-Health Implementation Toolkit (e-HIT) is an example of such a tool that was designed within the context of the United Kingdom National Health Service to promote implementation of e-health services. Its utility in international settings is unknown. METHODS: We conducted a qualitative evaluation of the e-HIT in use across four countries--Finland, Norway, Scotland, and Sweden. Data were generated using a combination of interview approaches (n = 22) to document e-HIT users' experiences of the tool to guide decision making about the selection of e-health pilot services and to monitor their progress over time. RESULTS: e-HIT users evaluated the tool positively in terms of its scope to organize and enhance their critical thinking about their implementation work and, importantly, to facilitate discussion between those involved in that work. It was easy to use in either its paper- or web-based format, and its visual elements were positively received. There were some minor criticisms of the e-HIT with some suggestions for content changes and comments about its design as a generic tool (rather than specific to sites and e health services). However, overall, e-HIT users considered it to be a highly workable tool that they found useful, which they would use again, and which they would recommend to other e-health implementers. CONCLUSION: The use of the e-HIT is feasible and acceptable in a range of international contexts by a range of professionals for a range of different e-health systems. PMID- 22098946 TI - Identification of candidate serum biomarkers for severe septic shock-associated kidney injury via microarray. AB - INTRODUCTION: Septic-shock-associated acute kidney injury (SSAKI) carries high morbidity in the pediatric population. Effective treatment strategies are lacking, in part due to poor detection and prediction. There is a need to identify novel candidate biomarkers of SSAKI. The objective of our study was to determine whether microarray data from children with septic shock could be used to derive a panel of candidate biomarkers for predicting SSAKI. METHODS: A retrospective cohort study compared microarray data representing the first 24 hours of admission for 179 children with septic shock with those of 53 age matched normal controls. SSAKI was defined as a >200% increase of baseline serum creatinine, persistent to 7 days after admission. RESULTS: Patients with SSAKI (n = 31) and patients without SSAKI (n = 148) were clinically similar, but SSAKI carried a higher mortality (45% vs. 10%). Twenty-one unique gene probes were upregulated in SSAKI patients versus patients without SSAKI. Using leave-one-out cross-validation and class prediction modeling, these probes predicted SSAKI with a sensitivity of 98% (95% confidence interval (CI) = 81 to 100) and a specificity of 80% (95% CI = 72 to 86). Serum protein levels of two specific genes showed high sensitivity for predicting SSAKI: matrix metalloproteinase-8 (89%, 95% CI = 64 to 98) and elastase-2 (83%, 95% CI = 58 to 96). Both biomarkers carried a negative predictive value of 95%. When applied to a validation cohort, although both biomarkers carried low specificity (matrix metalloproteinase-8: 41%, 95% CI = 28 to 50; and elastase-2: 49%, 95% CI = 36 to 62), they carried high sensitivity (100%, 95% CI = 68 to 100 for both). CONCLUSIONS: Gene probes upregulated in critically ill pediatric patients with septic shock may allow for the identification of novel candidate serum biomarkers for SSAKI prediction. PMID- 22098947 TI - Accuracy of b-GGT fraction for the diagnosis of non-alcoholic fatty liver disease. AB - BACKGROUND: Serum gamma-glutamyltransferase (GGT) activity is a sensitive but non specific marker of non-alcoholic fatty liver disease (NAFLD). Recently, four GGT fractions (big-, medium-, small-, free-GGT) were described in humans. AIM: We aimed to investigate whether a specific GGT fraction pattern is associated with NAFLD. METHODS: Gamma-glutamyltransferase fractions were determined in patients with NAFLD (n = 90), and compared with those in control subjects (n = 70), and chronic hepatitis C (CHC, n = 45) age and gender matched. RESULTS: Total GGT was elevated in NAFLD as compared to controls (median, 25 degrees -75 degrees percentile: 39.4, 20.0-82.0 U/L vs. 18.4, 13.2-24.9 U/L respectively, P < 0.001). All fractions were higher in NAFLD than in controls (P < 0.001). The b-GGT showed the highest diagnostic accuracy for NAFLD diagnosis [area under ROC curve (ROC AUC): 0.85; cut-off 2.6 U/L, sensitivity 74%, specificity 81%]. Also subjects with CHC showed increased GGT (41.5, 21.9-84.5 U/L, P < 0.001 vs. controls, P = n.s. vs. NAFLD), as well as m-, s-, and f-GGT, while b-GGT did not show any significant increase (P = n.s. vs. HS, P < 0.001 vs. NAFLD). In subjects with CHC, s-GGT showed the best diagnostic value (ROC-AUC: 0.853; cut-off 14.1 U/L, sensitivity 73%, specificity 90%). Serum GGT did not show any value in the differential diagnosis between NAFLD and CHC (ROC-AUC 0.507, P = n.s.), while b GGT/s-GGT ratio showed the highest diagnostic accuracy for distinguishing NAFLD and CHC (ROC-AUC: 0.93; cut-off value 0.16, sensitivity 82%, specificity 90%). CONCLUSIONS: b-GGT increases in NAFLD, but not in CHC. GGT fraction analysis might help in improving the sensitivity and specificity of the diagnosis of NAFLD and other liver dysfunctions. PMID- 22098948 TI - Spaceflight alters the gene expression profile of cervical cancer cells. AB - Our previous study revealed that spaceflight induced biological changes in human cervical carcinoma Caski cells. Here, we report that 48A9 cells, which were subcloned from Caski cells, experienced significant growth suppression and exhibited low tumorigenic ability after spaceflight. To further understand the potential mechanism at the transcriptional level, we compared gene expression between 48A9 cells and ground control Caski cells with suppression subtractive hybridization (SSH) and reverse Northern blotting methods, and analyzed the relative gene network and molecular functions with the Ingenuity Pathways Analysis (IPA) program. We found 5 genes, SUB1, SGEF, MALAT-1, MYL6, and MT-CO2, to be up-regulated and identified 3 new cDNAs, termed B4, B5, and C4, in 48A9 cells. In addition, we also identified the two most significant gene networks to indicate the function of these genes using the IPA program. To our knowledge, our results show for the first time that spaceflight can reduce the growth of tumor cells, and we also provide a new model for oncogenesis study. PMID- 22098949 TI - Knockdown of nucleophosmin induces S-phase arrest in HepG2 cells. AB - Nucleophosmin/B23 (NPM) is a universally expressed nucleolar phosphoprotein that participates in proliferation, apoptosis, ribosome assembly, and centrosome duplication; however, the role of NPM in cell cycle regulation is not well characterized. We investigated the mechanism by which NPM is involved in cell cycle regulation. NPM was knocked down using siRNA in HepG2 hepatoblastoma cells. NPM translocation following actinomycin D (ActD) treatment was investigated using immunofluorescent staining. Expression of NPM and other factors involved in cell cycle regulation was examined by Western blotting. Cell cycle distribution was measured using flow cytometry to detect 5-ethynyl-2'-deoxyuridine (EdU) incorporation. Cell proliferation was quantified by the MTT assay. Knockdown of NPM increased the percentage of HepG2 cells in S phase and led to decreased expression of P53 and P21Cip1/WAF1. S-phase arrest in HepG2 cells was significantly enhanced by ActD treatment. Furthermore, knockdown of NPM abrogated ActD-induced G2/M phase cell cycle arrest. Taken together, these data demonstrate that inhibition of NPM has a significant effect on the cell cycle. PMID- 22098951 TI - Overexpression of P-glycoprotein induces acquired resistance to imatinib in chronic myelogenous leukemia cells. AB - Imatinib, a breakpoint cluster region (BCR)-Abelson murine leukemia(ABL) tyrosine kinase inhibitor (TKI), has revolutionized the treatment of chronic myelogenous leukemia (CML). However, development of multidrug resistance(MDR) limits the use of imatinib. In the present study, we aimed to investigate the mechanisms of cellular resistance to imatinib in CML. Therefore, we established an imatinib resistant human CML cell line(K562-imatinib) through a stepwise selection process. While characterizing the phenotype of these cells, we found that K562 imatinib cells were 124.6-fold more resistant to imatinib than parental K562 cells. In addition, these cells were cross-resistant to second- and third generation BCR-ABL TKIs. Western blot analysis and reverse transcription polymerase chain reaction(RT-PCR) demonstrated that P-glycoprotein(P-gp) and MDR1 mRNA levels were increased in K562-imatinib cells. In addition, accumulation of [14C]6-mercaptopurine (6-MP) was decreased, whereas the ATP-dependent efflux of [14C]6-MP and [3H]methotrexate transport were increased in K562-imatinib cells. These data suggest that the overexpression of P-gp may play a crucial role in acquired resistance to imatinib in CML K562-imatinib cells. PMID- 22098953 TI - Re: Molecular stratification of clear cell renal cell carcinoma by consensus clustering reveals distinct subtypes and survival patterns. PMID- 22098950 TI - Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression. AB - Breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2) is an ATP-binding cassette (ABC) transporter identified as a molecular cause of multidrug resistance (MDR) in diverse cancer cells. BCRP physiologically functions as a part of a self-defense mechanism for the organism; it enhances elimination of toxic xenobiotic substances and harmful agents in the gut and biliary tract, as well as through the blood-brain, placental, and possibly blood testis barriers. BCRP recognizes and transports numerous anticancer drugs including conventional chemotherapeutic and targeted small therapeutic molecules relatively new in clinical use. Thus, BCRP expression in cancer cells directly causes MDR by active efflux of anticancer drugs. Because BCRP is also known to be a stem cell marker, its expression in cancer cells could be a manifestation of metabolic and signaling pathways that confer multiple mechanisms of drug resistance, self-renewal (stemness), and invasiveness (aggressiveness), and thereby impart a poor prognosis. Therefore, blocking BCRP-mediated active efflux may provide a therapeutic benefit for cancers. Delineating the precise molecular mechanisms for BCRP gene expression may lead to identification of a novel molecular target to modulate BCRP-mediated MDR. Current evidence suggests that BCRP gene transcription is regulated by a number of trans-acting elements including hypoxia inducible factor 1alpha, estrogen receptor, and peroxisome proliferator-activated receptor. Furthermore, alternative promoter usage, demethylation of the BCRP promoter, and histone modification are likely associated with drug-induced BCRP overexpression in cancer cells. Finally, PI3K/AKT signaling may play a critical role in modulating BCRP function under a variety of conditions. These biological events seem involved in a complicated manner. Untangling the events would be an essential first step to developing a method to modulate BCRP function to aid patients with cancer. This review will present a synopsis of the impact of BCRP-mediated MDR in cancer cells, and the molecular mechanisms of acquired MDR currently postulated in a variety of human cancers. PMID- 22098954 TI - Re: Feasibility of sentinel node detection in renal cell carcinoma: a pilot study. PMID- 22098955 TI - Re: Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy? PMID- 22098952 TI - Multidrug resistance associated proteins in multidrug resistance. AB - Multidrug resistance proteins (MRPs) are members of the C family of a group of proteins named ATP-binding cassette (ABC) transporters. These ABC transporters together form the largest branch of proteins within the human body. The MRP family comprises of 13 members, of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell. They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione (GSH), glucuronate, or sulphate. In addition, MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH. Collectively, MRPs can transport drugs that differ structurally and mechanistically, including natural anticancer drugs, nucleoside analogs, antimetabolites, and tyrosine kinase inhibitors. Many of these MRPs transport physiologically important anions such as leukotriene C4, bilirubin glucuronide, and cyclic nucleotides. This review focuses mainly on the physiological functions, cellular resistance characteristics, and probable in vivo role of MRP1 to MRP9. PMID- 22098957 TI - Re: Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the combination of avodart and tamsulosin trial. PMID- 22098958 TI - Re: Increased Cancer Risks for Relatives of Very Early-Onset Breast Cancer Cases With and Without BRCA1 and BRCA2 Mutations. PMID- 22098960 TI - Re: The use of zoledronic acid in men receiving androgen deprivation therapy for prostate cancer with severe osteopenia or osteoporosis. PMID- 22098962 TI - Re: Nerve Growth Factor Level in the Prostatic Fluid of Patients With Chronic Prostatitis/Chronic Pelvic Pain Syndrome is Correlated With Symptom Severity and Response to Treatment. PMID- 22098963 TI - Re: Tenderness as measured by pressure pain thresholds extends beyond the pelvis in chronic pelvic pain syndrome in men. PMID- 22098964 TI - Re: Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial. PMID- 22098965 TI - Re: A pilot study of botulinum toxin a for male chronic pelvic pain syndrome. PMID- 22098968 TI - Re: Does urinary stone composition and morphology help for prediction of primary hyperparathyroidism? PMID- 22098969 TI - Re: Dorsal onlay skin graft urethroplasty in patients older than 65 years. PMID- 22098970 TI - Re: Should being aged over 70 years hinder penile prosthesis implantation? PMID- 22098971 TI - Re: Association between implementation of a medical team training program and surgical mortality. PMID- 22098973 TI - Re: Antimuscarinics and bladder outlet obstruction: from a contraindication to an indication? PMID- 22098975 TI - Re: Complementary and Alternative Medicine (CAM) Use in Women With Pelvic Floor Disorders: A Cohort Study. PMID- 22098976 TI - Re: Can pelvic floor muscle training reverse pelvic organ prolapse and reduce prolapse symptoms? An assessor-blinded, randomized, controlled trial. PMID- 22098977 TI - Re: Treatment Outcomes and Resource Use of Patients With Neurogenic Detrusor Overactivity Receiving Botulinum Toxin A (BOTOX) Therapy in Germany. PMID- 22098978 TI - Re: Intravesical prostatic protrusion predicts clinical progression of benign prostatic enlargement in patients receiving medical treatment. PMID- 22098979 TI - Re: Symptomatic and quality of life response to tolterodine in subgroups of men with overactive bladder symptoms and presumed non-obstructive benign prostatic hyperplasia. PMID- 22098980 TI - Re: Safety of Physiological Testosterone Therapy in Women: Lessons From Female-to Male Transsexuals (FMT) Treated With Pharmacological Testosterone Therapy. PMID- 22098981 TI - Re: Behavior and symptom change among women treated with placebo for sexual dysfunction. PMID- 22098984 TI - Re: Clinical significance of sperm DNA damage in assisted reproduction outcome. PMID- 22098985 TI - Re: DNA fragmentation of normal spermatozoa negatively impacts embryo quality and intracytoplasmic sperm injection outcome. PMID- 22098986 TI - Re: Y chromosome microdeletions, sperm DNA fragmentation and sperm oxidative stress as causes of recurrent spontaneous abortion of unknown etiology. PMID- 22098987 TI - Re: Sperm DNA integrity in cancer patients before and after cytotoxic treatment. PMID- 22098988 TI - Re: Radical soft tissue mobilization and reconstruction (kelly procedure) for bladder exstrophy repair in males: initial experience with nine cases. PMID- 22098989 TI - Re: Pelvic-floor imaging using three-dimensional ultrasonography and magnetic resonance imaging in the long term follow-up of the bladder-exstrophy-epispadias complex. PMID- 22098990 TI - Re: The meatal/urethral width in healthy uncircumcised boys. PMID- 22098991 TI - Re: eIF4E Phosphorylation Promotes Tumorigenesis and is Associated With Prostate Cancer Progression. PMID- 22098992 TI - Re: Fkbp52 regulates androgen receptor transactivation activity and male urethra morphogenesis. PMID- 22098993 TI - Man with rash and nausea. Acute generalized exanthematous pustulosis after cephalexin use. PMID- 22098994 TI - Is discharge to home after emergency department cardioversion safe for the treatment of recent-onset atrial fibrillation? AB - Recent-onset atrial fibrillation, defined as a first detected or recurrent episode of atrial fibrillation lasting less than 48 hours, is a commonly encountered dysrhythmia in the emergency department (ED). Cardioversion of stable patients in the ED with recent-onset atrial fibrillation without antecedent anticoagulation would allow for these patients to be discharged directly to home. We searched the literature to determine whether any studies have investigated the safety of this management strategy and identified five that addressed this question. These studies are reviewed herein; importantly, not one ED patient who was cardioverted in any of the five studies suffered a thromboembolic event - the feared complication responsible for most of the controversy surrounding the ED management of atrial fibrillation. According to the available evidence, we conclude that it would be within the standard of care to discharge home stable patients with recent-onset atrial fibrillation after cardioversion in the ED with adequate follow-up. It should be noted that although this strategy is safe and effective, the return visit rate for relapsed atrial fibrillation is 3% to 17%, and patients should be made aware of this possibility. PMID- 22098995 TI - Evaluation of the Test-mate ChE (cholinesterase) field kit in acute organophosphorus poisoning. AB - STUDY OBJECTIVE: Measurement of acetylcholinesterase (AChE) is recommended in the management of organophosphorus poisoning, which results in 200,000 deaths worldwide annually. The Test-mate ChE 400 is a portable field kit designed for detecting occupational organophosphorus exposure that measures RBC AChE and plasma cholinesterase (PChE) within 4 minutes. We evaluate Test-mate against a reference laboratory test in patients with acute organophosphorus self-poisoning. METHODS: This was a cross-sectional comparison study of 14 patients with acute organophosphorus poisoning between May 2007 and June 2008. RBC AChE and PChE were measured in 96 and 91 samples, respectively, with the Test-mate ChE field kit and compared with a reference laboratory, using the limits of agreement method (Bland and Altman), kappa statistics, and Spearman's correlation coefficients. RESULTS: There was good agreement between the Test-mate ChE and the reference laboratory for RBC AChE. The mean difference (Test-mate-reference) was -0.62 U/g hemoglobin, 95% limits of agreement -10.84 to 9.59 U/g hemoglobin. Good agreement was also observed between the categories of mild, moderate, and severe RBC AChE inhibition (weighted kappa 0.85; 95% confidence interval [CI] 0.83 to 0.87). Measurement of PChE also showed good agreement, with a mean difference (Test-mate-reference) of +0.06 U/mL blood, 95% limits of agreement -0.41 to 0.53 U/mL blood. Spearman's correlation coefficients were 0.87 (95% CI 0.81 to 0.91) for RBC AChE and 0.76 (95% CI 0.66 to 0.84) for PChE. Analysis for within-subject correlation of subjects did not change the limits of agreement. CONCLUSION: The Test-mate ChE field kit reliably provides rapid measurement of RBC AChE in acute organophosphorus poisoning. PMID- 22098996 TI - Commentary: characteristics of LEOs' fatalities in motor vehicle crashes: a lack of safety culture in LEOs is a loss for us all. PMID- 22098997 TI - Change of shift. Death by slow, better fast. PMID- 22098998 TI - Man with shoulder pain after a fall. Necrotizing fasciitis. PMID- 22098999 TI - Reperfusion is delayed beyond guideline recommendations in patients requiring interhospital helicopter transfer for treatment of STEMI. PMID- 22099001 TI - International emergency medicine and global health: training and career paths for emergency medicine residents. PMID- 22099003 TI - Unilateral facial swelling with fever. Parotitis. PMID- 22099005 TI - Adherence to artemether/lumefantrine treatment in children under real-life situations in rural Tanzania. AB - A follow-up study was conducted to determine the magnitude of and factors related to adherence to artemether/lumefantrine (ALu) treatment in rural settings in Tanzania. Children in five villages of Kilosa District treated at health facilities were followed-up at their homes on Day 7 after the first dose of ALu. For those found to be positive using a rapid diagnostic test for malaria and treated with ALu, their caretakers were interviewed on drug administration habits. In addition, capillary blood samples were collected on Day 7 to determine lumefantrine concentrations. The majority of children (392/444; 88.3%) were reported to have received all doses, in time. Non-adherence was due to untimeliness rather than missing doses and was highest for the last two doses. No significant difference was found between blood lumefantrine concentrations among adherent (median 286 nmol/l) and non-adherent [median 261 nmol/l; range 25 nmol/l (limit of quantification) to 9318 nmol/l]. Children from less poor households were more likely to adhere to therapy than the poor [odds ratio (OR)=2.45, 95% CI 1.35-4.45; adjusted OR=2.23, 95% CI 1.20-4.13]. The high reported rate of adherence to ALu in rural areas is encouraging and needs to be preserved to reduce the risk of emergence of resistant strains. The age-based dosage schedule and lack of adherence to ALu treatment guidelines by health facility staff may explain both the huge variability in observed lumefantrine concentrations and the lack of difference in concentrations between the two groups. PMID- 22099004 TI - Strengthening relationships: amyloids create adhesion nanodomains in yeasts. AB - Budding yeasts adhere to biotic or abiotic surfaces and aggregate to form biofilms, using wall-anchored glycoprotein adhesins. The process is paradoxical: adhesins often show weak binding to specific ligands, yet mediate remarkably strong adherence. Single-molecule atomic force microscopy (AFM), genomics, biochemistry and cell biology have recently explained the puzzle, with Candida albicans Als adhesins as the paradigm. The strength of adhesion results partly from force-activated amyloid-like clustering of hundreds of adhesin molecules to form arrays of ordered multimeric binding sites. The various protein domains of eukaryotic adhesins cooperate to facilitate this fascinating new mechanism of activation. PMID- 22099006 TI - Attaching and effacing Escherichia coli and Shiga toxin-producing E. coli in children with acute diarrhoea and controls in Teresina/PI, Brazil. AB - This 3.5-year prospective study was conducted to ascertain the level of attaching and effacing Escherichia coli (AEEC) associated diarrhoea in children from Teresina, a northeastern state of Brazil. Passed faecal specimens from 400 patients (250 with and 150 without diarrhoea) up to 60 months of age attending from 2004 to 2007 at two public hospitals were investigated. Conventional microbiology methods and PCR were employed. Escherichia coli was isolated from 390 children, 240 of them with diarrhoea. A total of 117 AEEC strains were cultivated from specimens from 63 children, 37 with and 26 without diarrhoea. No association between AEEC and diarrhoea was observed. Atypical enteropathogenic E. coli (a-EPEC) (79.4%) was more commonly found than typical EPEC (t-EPEC). Association between EPEC and EPEC subtypes and diarrhoea was not detected. Mixed infection by t-EPEC and a-EPEC and infection by Shiga toxin-producing E. coli (STEC) were rare. Enteropathogenic E. coli was more common in males and in children aged less than 12 months. Correlation between serotyping and PCR results was 0.19. High resistance rates of AEEC to ampicillin, cephalotin, and trimethoprim-sulfamethoxazole were found. In conclusion, EPEC is very common in children with diarrhoea and controls in the population we studied, with a-EPEC predominating. This diarrhoeagenic E. coli (DEC) pathotype is more common in infant males and is resistant to drugs frequently used in clinical practice. PMID- 22099007 TI - Introduction. Demand for central venous access. PMID- 22099008 TI - A concise history of central venous access. AB - Central venous access has become a mainstay of modern interventional radiology practice. Its history has paralleled and enabled many current medical therapies. This short overview provides an interesting historical perspective of these increasingly common interventional procedures. PMID- 22099009 TI - Principles of non-tunneled central venous access. AB - Non-tunneled central venous access has become an important tool in the management of the sick patient, particularly in the intensive care unit. Image guidance allows more precise placement of lines with overall lower complication rates compared with guidance by physical landmarks. The use of image guidance has brought a procedure traditionally performed by surgeons into the realm of the interventional radiologist. Techniques for placement of non-tunneled central venous catheters, hemodialysis catheters, and peripherally inserted central catheter lines will be discussed. PMID- 22099010 TI - Principles of tunneled cuffed catheter placement. AB - Tunneled cuffed catheters provide reliable and instant long-term intravenous access for a large variety of therapeutic purposes, including chemotherapy, parenteral nutrition, and apheresis. The most frequent application is for patients with renal failure as an access device for hemodialysis. In this capacity, the rate of catheter use has remained stable in the United States, despite the promotion of arteriovenous fistulas and arteriovenous grafts. The latter 2 procedures achieve superior longevity and much higher cost-efficiency. Tunneled catheters, however, serve as bridging devices during maturation of newly placed arteriovenous fistulas or as the final option in patients in whom fistulas and grafts have failed. High-quality vascular access is a hallmark of interventional radiology, and its significance for patient care and for our specialty cannot be overestimated. Familiarity with basic concepts of the device and procedural techniques are crucial to achieve successful long-term venous access. The following article demonstrates key concepts of tunneled venous catheter placement by means of dialysis, inasmuch as dialysis catheters represent the most commonly placed tunneled central venous catheters. The principles of placement and techniques utilized, however, are applicable to devices that are used for chemotherapy or parenteral nutrition, such as the Hickman, Broviac, Groshong, or tunneled peripherally inserted central catheters. PMID- 22099011 TI - Principles of subcutaneous port placement. AB - The introduction of totally implantable subcutaneous devices in the early 1980s provided patients with secure, reliable venous access and also gave them the ability to move more freely and have a more normal lifestyle with these devices in place. The most common totally implantable device used today is the subcutaneous port. These ports consist of an injection port connected to a catheter. Ports provide a number of advantages compared with other venous catheters; the most important is the reduced risk of infection. These devices have significantly lower rates of infection than nontunneled and tunneled catheters. Additional advantages include less frequent irrigation and minimal home care, and they are less prone to environmental or cutaneous contamination when not being accessed. This article will focus on the placement of these ports. PMID- 22099012 TI - Peripherally inserted central catheter placement in infants and children. AB - The most common venous access procedure performed in children and infants is the peripherally inserted central catheter, or "PICC." Placement of a PICC affords patients stable long-term venous access for medication administration and blood draws. The Interventional Radiology team faces particular challenges in the placement and management of these catheters in a pediatric population. This article discusses our institution's step-by-step approach to operating a hospital wide PICC service. PMID- 22099013 TI - Diagnosis and treatment of central venous access-associated infections. AB - This paper provides readers with a basic understanding of the types of central venous access-associated infections as well as appropriate diagnostic techniques. Preventive measures are the most effective way to reduce rates of catheter associated infection and are discussed in detail. Diagnosis and treatment of each type of infection are reviewed for nontunneled central venous catheters, tunneled dialysis catheters, and venous access ports. Readers should be able to employ the methods described in this paper to reduce the rate of central venous access associated infections at their hospitals. PMID- 22099014 TI - Evaluation and management of central venous access complications. AB - Venous access is 1 of the most common interventional procedures in the USA. Using image guidance in the last 2 decades, obtaining venous access has become increasingly routine, and the complications commonly associated with the procedure have significantly decreased. However, interventional radiologists still encounter both early and late complications routinely associated with both central and peripherally inserted access devices. This article discusses the most common and some unusual complications seen with the placement of these devices. We also briefly discuss the management of these complications. PMID- 22099015 TI - Venous access salvage techniques. AB - For patients who need long-term central venous access but who have developed obstruction of the usual central veins, "salvage" access techniques offer successful alternatives. These techniques include translumbar inferior vena cava access, transhepatic inferior vena cava access, catheterization of small venous collaterals, and recanalization of occluded veins. Inferior vena cava access techniques allow a range of devices to be placed, including ports, infusion catheters, and hemodialysis catheters. Collateral vessels may be too small to allow for large-caliber devices, such as hemodialysis catheters. Success rates for these access techniques are high and complications are infrequent. These access routes are in general quite durable. Adults and children can be treated. Once placed, devices are managed and used as they would be for any routinely placed venous access device. PMID- 22099016 TI - On the origin of hematopoietic stem cells: progress and controversy. AB - Hematopoietic Stem Cells (HSCs) are responsible for the production and replenishment of all blood cell types during the entire life of an organism. Generated during embryonic development, HSCs transit through different anatomical niches where they will expand before colonizing in the bone marrow, where they will reside during adult life. Although the existence of HSCs has been known for more than fifty years and despite extensive research performed in different animal models, there is still uncertainty with respect to the precise origins of HSCs. We review the current knowledge on embryonic hematopoiesis and highlight the remaining questions regarding the anatomical and cellular identities of HSC precursors. PMID- 22099017 TI - Conditionally immortalised neural stem cells promote functional recovery and brain plasticity after transient focal cerebral ischaemia in mice. AB - Cell therapy has enormous potential to restore neurological function after stroke. The present study investigated effects of conditionally immortalised neural stem cells (ciNSCs), the Maudsley hippocampal murine neural stem cell line clone 36 (MHP36), on sensorimotor and histological outcome in mice subjected to transient middle cerebral artery occlusion (MCAO). Adult male C57BL/6 mice underwent MCAO by intraluminal thread or sham surgery and MHP36 cells or vehicle were implanted into ipsilateral cortex and caudate 2 days later. Functional recovery was assessed for 28 days using cylinder and ladder rung tests and tissue analysed for plasticity, differentiation and infarct size. MHP36-implanted animals showed accelerated and augmented functional recovery and an increase in neurons (MAP-2), synaptic plasticity (synaptophysin) and axonal projections (GAP 43) but no difference in astrocytes (GFAP), oligodendrocytes (CNPase), microglia (IBA-1) or lesion volumes when compared to vehicle group. This is the first study showing a potential functional benefit of the ciNSCs, MHP36, after focal MCAO in mice, which is probably mediated by promoting neuronal differentiation, synaptic plasticity and axonal projections and opens up opportunities for future exploitation of genetically altered mice for dissection of mechanisms of stem cell based therapy. PMID- 22099018 TI - Bcl-xL enhances single-cell survival and expansion of human embryonic stem cells without affecting self-renewal. AB - Robust expansion and genetic manipulation of human embryonic stem cells (hESCs) and induced-pluripotent stem (iPS) cells are limited by poor cell survival after enzymatic dissociation into single cells. Although inhibition of apoptosis is implicated for the single-cell survival of hESCs, the protective role of attenuation of apoptosis in hESC survival has not been elucidated. Bcl-xL is one of several anti-apoptotic proteins, which are members of the Bcl-2 family of proteins. Using an inducible system, we ectopically expressed Bcl-xL gene in hESCs, and found a significant increase of hESC colonies in the single-cell suspension cultures. Overexpression of Bcl-xL in hESCs decreased apoptotic caspase-3(+) cells, suggesting attenuation of apoptosis in hESCs. Without altering the kinetics of pluripotent gene expression, the efficiency to generate embryoid bodies (EBs) in vitro and the formation of teratoma in vivo were significantly increased in Bcl-xL-overexpressing hESCs after single-cell dissociation. Interestingly, the number and size of hESC colonies from cluster cultures were not affected by Bcl-xL overexpression. Several genes of extracellular matrix and adhesion molecules were upregulated by Bcl-xL in hESCs without single-cell dissociation, suggesting that Bcl-xL regulates adhesion molecular expression independent of cell dissociation. In addition, the gene expressions of FAS and several TNF signaling mediators were downregulated by Bcl xL. These data support a model in which Bcl-xL promotes cell survival and increases cloning efficiency of dissociated hESCs without altering hESC self renewal by i) attenuation of apoptosis, and ii) upregulation of adhesion molecules to facilitate cell-cell or cell-matrix interactions. PMID- 22099019 TI - Directing migration of endothelial progenitor cells with applied DC electric fields. AB - Naturally-occurring, endogenous electric fields (EFs) have been detected at skin wounds, damaged tissue sites and vasculature. Applied EFs guide migration of many types of cells, including endothelial cells to migrate directionally. Homing of endothelial progenitor cells (EPCs) to an injury site is important for repair of vasculature and also for angiogenesis. However, it has not been reported whether EPCs respond to applied EFs. Aiming to explore the possibility to use electric stimulation to regulate the progenitor cells and angiogenesis, we tested the effects of direct-current (DC) EFs on EPCs. We first used immunofluorescence to confirm the expression of endothelial progenitor markers in three lines of EPCs. We then cultured the progenitor cells in EFs. Using time-lapse video microscopy, we demonstrated that an applied DC EF directs migration of the EPCs toward the cathode. The progenitor cells also align and elongate in an EF. Inhibition of vascular endothelial growth factor (VEGF) receptor signaling completely abolished the EF-induced directional migration of the progenitor cells. We conclude that EFs are an effective signal that guides EPC migration through VEGF receptor signaling in vitro. Applied EFs may be used to control behaviors of EPCs in tissue engineering, in homing of EPCs to wounds and to an injury site in the vasculature. PMID- 22099021 TI - Comprehensive transcriptome and immunophenotype analysis of renal and cardiac MSC like populations supports strong congruence with bone marrow MSC despite maintenance of distinct identities. AB - Cells resembling bone marrow mesenchymal stem cells (MSC) have been isolated from many organs but their functional relationships have not been thoroughly examined. Here we compared the immunophenotype, gene expression, multipotency and immunosuppressive potential of MSC-like colony-forming cells from adult murine bone marrow (bmMSC), kidney (kCFU-F) and heart (cCFU-F), cultured under uniform conditions. All populations showed classic MSC morphology and in vitro mesodermal multipotency. Of the two solid organ-specific CFU-F, only kCFU-F displayed suppression of T-cell alloreactivity in vitro, albeit to a lesser extent than bmMSC. Quantitative immunophenotyping using 81 phycoerythrin-conjugated CD antibodies demonstrated that all populations contained high percentages of cells expressing diagnostic MSC surface markers (Sca1, CD90.2, CD29, CD44), as well as others noted previously on murine MSC (CD24, CD49e, CD51, CD80, CD81, CD105). Illumina microarray expression profiling and bioinformatic analysis indicated a correlation of gene expression of 0.88-0.92 between pairwise comparisons. All populations expressed approximately 66% of genes in the pluripotency network (Plurinet), presumably reflecting their stem-like character. Furthermore, all populations expressed genes involved in immunomodulation, homing and tissue repair, suggesting these as conserved functions for MSC-like cells in solid organs. Despite this molecular congruence, strong biases in gene and protein expression and pathway activity were seen, suggesting organ-specific functions. Hence, tissue-derived MSC may also retain unique properties potentially rendering them more appropriate as cellular therapeutic agents for their organ of origin. PMID- 22099020 TI - Derivation of functional ventricular cardiomyocytes using endogenous promoter sequence from murine embryonic stem cells. AB - The purpose of this study is to establish a murine embryonic stem cell (mESC) line for isolation of functional ventricular cardiomyocytes (VCMs) and then to characterize the derived VCMs. By crossing the myosin light chain 2v (Mlc2v)-Cre mouse line with the reporter strain Rosa26-yellow fluorescent protein (YFP), we generated mESC lines from these double transgenic mice, in which Cre-mediated removal of a stop sequence results in the expression of YFP under the control of the ubiquitously active Rosa26 promoter specifically in the VCM. After induction of differentiation via embryoid body (EB) formation, contracting YFP(+) cells were detected within EBs and isolated by fluorescence-activated cell sorting. N cadherin, the cadherin expressed in cardiomyocytes, and the major cardiac connexin (Cx) isoform, Cx43, were detected in the respective adherens and gap junctions in these VCMs. Using current clamp recordings we demonstrated that mESC derived VCMs exhibited action potential characteristics comparable to those of neonatal mouse VCMs. Real-time intracellular calcium [Ca(2+)](i) imaging showed rhythmic intracellular calcium transients in these VCMs. The amplitude and frequency of calcium transients were increased by isoproterenol stimulation, suggesting the existence of functional beta-adrenergic signaling. Moreover, [Ca(2+)](i) oscillations responded to increasing frequencies of external electrical stimulation, indicating that VCMs have functional excitation contraction coupling, a key factor for the ultimate cardiac contractile performance. The present study makes possible the production of homogeneous and functional VCMs for basic research as well as for cardiac repair and regeneration. PMID- 22099022 TI - Clonal multipotency and effect of long-term in vitro expansion on differentiation potential of human hair follicle derived mesenchymal stem cells. AB - Hair follicle harbors a rich stem cell pool with mesenchymal lineage differentiation potential. Although previous studies with rodent cells demonstrated that hair follicle sheath and papilla cells possess multi-lineage differentiation potential, human hair follicle derived mesenchymal stem cells (hHF-MSCs) have not been characterized in detail in terms of their multipotency. In addition, it is not clear whether these cells are true stem cells that can differentiate along multiple lineages or whether they represent a collection of progenitor cells with restricted differentiation potential. Here we report that hHF-MSCs are highly proliferative cells that can be maintained in culture for ~45 population doublings before they start to show signs of cellular senescence. Under appropriate culture conditions, hHF-MSCs differentiated along the myogenic, osteogenic, adipogenic and chondrogenic lineages, as demonstrated by kinetic gene expression profiling and functional assays. Interestingly, the differentiation potential decreased with time in culture in a lineage-specific manner. Specifically, myogenesis and chondrogenesis showed a moderate decrease over time; osteogenesis was maximum at intermediate passages and adipogenesis was highly sensitive to long-term culture and was diminished at late passages. Finally, hHF MSCs were clonally multipotent as the majority of hHF-MSCs clones (73%) demonstrated bi- or tri-lineage differentiation potential. These results suggest that hHF-MSCs may present as an alternative source of easily accessible, autologous stem cells for tissue engineering and regenerative medicine. PMID- 22099023 TI - Endoglin is a novel endothelial cell specification gene. AB - Endothelial cells (EC) are important in vasculogenesis and organogenesis during development and in the pathogenesis of cancer and cardiovascular diseases. However, few EC specification factors are known and primary EC production remains inefficient. Based on recent studies implicating endoglin (Eng) in early vascular development and angiogenesis, we hypothesized that Eng may be an EC specification gene. Mouse embryonic stem cells (ESC) were treated with recombinant Eng or a plasmid expressing the Eng ORF, and differentiated in the presence or absence of bone morphogenic protein 4 (BMP4). Expression of the mesoderm and EC marker genes, the known mediators of EC specification and their downstream targets was monitored by quantitative PCR, western blot, immunocytochemistry, and flow cytometry. Functionality of the differentiated EC was assessed by in vitro angiogenesis assay and the induction of Icam1 expression in response to TNF-alpha treatment. Both recombinant Eng and forced Eng expression increased the number of functional EC expressing the EC marker genes VE-cadherin, vWF, and Tie2, and enhanced the effect of BMP4. The Eng-induced EC differentiation was independent of known mediators of EC specification such as Indian Hedgehog (IHH) and BMP4 or of BMP4/Smad1/5/8 signaling. These studies suggest that Eng is a novel EC specification gene. PMID- 22099026 TI - Differentiation of human ES cell-derived neural progenitors to neuronal cells with regional specific identity by co-culturing of notochord and somite. AB - Limitations to the in vivo study of human nervous system development make it necessary to design an in vitro model to evaluate the in vivo effects of surrounding tissues on neurogenesis and regional identity of the human neural plate. Rostral neural progenitors (NPs) were initially generated from adherent human embryonic stem cells (hESCs) in a defined condition and characterized. Then, to find the role of somites (S) and notochords (N) in rostro-caudal (RC) and dorso-ventral (DV) patterning of neuronal cells, NPs were co-cultured with microencapsulated chicken S or N in alginate beads. In this study, N induced more neurogenesis as evaluated by expression of TUJ1 and MAP2-positive cells. Additionally, N induced spinal cord ventral brachiothoracic identity as well as NPs proliferation. We observed a synergic effect on motoneuron induction when S and N were used together. Moreover, S induced hindbrain identity in differentiated neuronal cells from NPs. These results indicate that highly enriched NPs can be generated in an adherent and defined system from hESCs. Moreover, S and N tissues highly influenced neuronal differentiation in point of proliferation, neurogenesis, and RC and DV regional identity. These results indicate a very simple and efficient protocol to mimic in vivo events of human neural development in vitro which is important in the context of developmental neuroscience and cellular replacement therapies. PMID- 22099024 TI - Laminin-511 expression is associated with the functionality of feeder cells in human embryonic stem cell culture. AB - Fibroblast feeder cells play an important role in supporting the derivation and long term culture of undifferentiated, pluripotent human embryonic stem cells (hESCs). The feeder cells secrete various growth factors and extracellular matrix (ECM) proteins into extracellular milieu. However, the roles of the feeder cell secreted factors are largely unclear. Animal feeder cells and use of animal serum also make current feeder cell culture conditions unsuitable for derivation of clinical grade hESCs. We established xeno-free feeder cell lines using human serum (HS) and studied their function in hESC culture. While human foreskin fibroblast (hFF) feeder cells were clearly hESC supportive, none of the established xeno-free human dermal fibroblast (hDF) feeder cells were able to maintain undifferentiated hESC growth. The two fibroblast types were compared for their ECM protein synthesis, integrin receptor expression profiles and key growth factor secretion. We show that hESC supportive feeder cells produce laminin-511 and express laminin-binding integrins alpha3beta1, alpha6beta1 and alpha7beta1. These results indicate specific laminin isoforms and integrins in maintenance of hESC pluripotency in feeder-dependent cultures. In addition, several genes with a known or possible role for hESC pluripotency were differentially expressed in distinct feeder cells. PMID- 22099027 TI - Induced pluripotent stem cells from hair follicles as a cellular model for neurodevelopmental disorders. AB - Disease-specific induced pluripotent stem cells (iPSC) allow unprecedented experimental platforms for basic research as well as high-throughput screening. This may be particularly relevant for neuropsychiatric disorders, in which the affected neuronal cells are not accessible. Keratinocytes isolated from hair follicles are an ideal source of patients' cells for reprogramming, due to their non-invasive accessibility and their common neuroectodermal origin with neurons, which can be important for potential epigenetic memory. From a small number of plucked human hair follicles obtained from two healthy donors we reprogrammed keratinocytes to pluripotent iPSC. We further differentiated these hair follicle derived iPSC to neural progenitors, forebrain neurons and functional dopaminergic neurons. This study shows that human hair follicle-derived iPSC can be differentiated into various neural lineages, suggesting this experimental system as a promising in vitro model to study normal and pathological neural developments, avoiding the invasiveness of commonly used skin biopsies. PMID- 22099025 TI - Rare corneal clones in mice suggest an age-related decrease of stem cell activity and support the limbal epithelial stem cell hypothesis. AB - The anterior ocular surface comprises the cornea, conjunctiva and a narrow intermediate region called the limbus. It is widely accepted that the corneal epithelium is maintained by stem cells but different hypotheses propose that the stem cells that maintain the mouse corneal epithelium during normal homeostasis are located either in the basal limbal epithelium or throughout the basal corneal epithelium. There are no specific markers to help test these alternatives and new methods are required to distinguish between them. We observed that KRT5(LacZ/-) transgenic mice produced rare beta-galactosidase (beta-gal)-positive radial stripes in the corneal epithelium. These stripes are likely to be clonal lineages of cells derived from stem cells, so they provide a lineage marker for actively proliferating stem cells. The distributions of the beta-gal-positive radial stripes suggested they extended centripetally from the limbus, supporting the limbal epithelial stem cell (LESC) hypothesis. Stripe frequency declined between 15 and 30 weeks, which predicts a reduction in stem cell function with age. Pax6(+/-), KRT5(LacZ/-) corneas had small patches rather than stripes, which confirms that corneal maintenance is abnormal in Pax6(+/-) mice. PMID- 22099028 TI - Is time on cardiopulmonary bypass during cardiac surgery associated with acute kidney injury requiring dialysis? AB - It is commonly accepted that the longer the time on extracorporeal cardiopulmonary bypass (CPB), the higher is the likelihood of developing acute renal failure requiring dialysis (ARF-D). Nonetheless, previous works elicited conflicting evidence. We investigated the relationship between CPB duration and ARF-D occurrence. Data were extracted from a large observational study. All factors independently associated with ARF-D were detected. Overall, 11,092 case record forms were analyzed. At the univariate analyses, time on CBP was associated with an increase in the ARF-D risk (odds ratio of fifth vs. first quintile of CBP time: 3.84; 95% confidence interval: 2.58-5.7; P < 0.001). However, after adjusting for confounders, the association between time on CBP and ARF-D lost its statistical significance. In this large dataset, CBP time did not predict ARF-D occurrence. These results might suggest that an accurate risk assessment might be more important than time on CPB in determining ARF-D occurrence.